PMID- 15971514
TI  - Sex condoms and STDs among young people.

PMID- 15971515
TI  - Food insecurity.

PMID- 15971516
TI  - Youth smoking.

PMID- 15971517
TI  - Mannanoligosaccharides and aflatoxin B1 in feed for laying hens: effects on egg
      quality, aflatoxins B1 and M1 residues in eggs, and aflatoxin B1 levels in liver.
AB  - Ninety-six laying hens were allocated to 4 groups and fed diets (control diet (0
      0), diet supplemented with 2.5 ppm aflatoxin B1 (0-AF); diet supplemented with
      0.11% mannanoligosaccharide (MOS-0); diet supplemented with 0.11% MOS and 2.5 ppm
      aflatoxin B1 (MOS-AF) for 4 wk to evaluate the effect of aflatoxin B1 (AFB1),
      mannanoligosaccharide (MOS), or both on egg quality and the in vivo efficacy of
      MOS to interact with an oral administration of AFB1. After 2 and 3 wk, egg weight
      decreased (P < 0.05) in the group fed MOS-0 versus groups on 0-0 and 0-AF. Egg
      shell weight was lower (P < 0.05) in the group fed 0-AF. Aflatoxin influenced
      color parameters, which were probably related to interference of AFB1 with lipid
      metabolism and pigmentary substances deposition in yolk. MOS appeared to increase
      protein percentage in albumen. No AFB1 or aflatoxin M1 (AFM1; a polar metabolite
      of AFB1) residues were found in eggs of the experimental groups. Livers from
      groups 0-0 and MOS-0 always tested negative for AFB1 and AFM1. Differences (P <
      0.01) were found between AFB1 hepatic levels of group 0-AF (mean +/- SD: 4.13 +/-
      1.95 ppb) and group MOS-AF (mean +/- SD: 2.21 +/- 1.37 ppb). The data
      demonstrated the ability of MOS to adsorb and degrade AFB1, reducing
      gastrointestinal absorption of AFB1 and its levels in tissues.

PMID- 15971518
TI  - Effect of age and housing system on genetic parameters for broiler carcass
      traits.
AB  - The effect of age and housing system on genetic parameters for BW and carcass
      traits was investigated. Traits were measured on broilers of different ages (48,
      63, and 70 d). Birds in the 48 and 70 d groups were raised in group housing,
      whereas birds in the 63 d group were raised in the same housing up to 22 d and in
      individual cages between 22 and 63 d. Each group consisted of approximately 2,000
      individuals from a single group of parents. Carcass, breast meat, abdominal fat,
      and back half were expressed as percentage of BW. The heritabilities of BW at 48,
      63, and 70 d were 0.31, 0.26, and 0.19, respectively, and the heritabilities of
      back half percentage at 48, 63, and 70 d were 0.42, 0.38, and 0.21, respectively.
      For other carcass traits, heritabilities were in the same range in different age
      groups. A positive genetic correlation was found between BW and valuable parts of
      carcass (breast meat and back half) at 48 d; these relationships were negative at
      70 d. The genetic correlation between BW and abdominal fat percentage at 70 d was
      higher than at 48 d. The increase in growth at 48 d was accompanied by increase
      in valuable parts; at 70 d it was accompanied by an increase in abdominal fat
      percentage. The genetic correlation of BW at 48 d between individual cage and
      group housing demonstrated a genotype by environment interaction for performance
      of birds, which has consequences for design of breeding schemes.

PMID- 15971519
TI  - Association of polymorphisms for prolactin and prolactin receptor genes with
      broody traits in chickens.
AB  - Prolactin (PRL) is generally accepted as crucial to the onset and maintenance of
      broodiness in avian species. The prolactin receptor (PRLR) plays an important
      role in the PRL signal transduction cascade. Two candidate genes, PRL and PRLR,
      were screened for polymorphisms in the chicken, and their genetic effects on
      broodiness were evaluated. Pedigreed hens (n = 155) of the Blue-shell chicken, a
      Chinese local breed, were observed for phenotypic broody traits including nesting
      days, broody days, repeats of broody cycles, and duration of broodiness. For
      polymorphism analysis, White Leghorns, Hy-Line brown egg layers, Avian broilers,
      and some other Chinese local breeds were included. Fifteen sets of primers were
      used to amplify the nucleotide sequences of the promotor of PRL and exons of
      PRLR. The PCR products were screened for polymorphisms using single-stranded
      conformational polymorphism protocol. Sequencing revealed a 24-bp insertion
      occurring in the promotor, -377 approximately -354, of PRL (GenBank accession no.
      AB011434). A single nucleotide polymorphism (SNP), A9026G (GenBank accession no.
      AY237377), in exon 3 of PRLR was also detected, which led to a nucleotide
      transition in the 5'-untranslated region (5'-UTR) of PRLR cDNA. Two SNP, T14771C
      and G14820A (GenBank accession no. AY237376), were detected in exon 6 of the
      PRLR. The T14771C transition led to an amino acid variation, Leu340Ser, in PRLR,
      whereas the G14820A transition was a synonymous mutation. An association analysis
      showed that the genetic polymorphisms at PRLR3 and PRLR6 were not related to
      broodiness (P > 0.05), whereas the individuals without the insertion sequence at
      PRLpro2 were associated with broody traits (P < 0.05) and the incidence (>30%) of
      typical broody of genotypes +/- and -/- was higher (P < 0.01) than that of +/+.
      In addition, all White Leghorns were +/+ for PRLpro2, whereas local breeds with
      very strong broodiness were nearly all -/-. Homozygous insertion of the 24-bp
      sequence in the PRL promoter may decrease the expression of PRL, leading to
      nonbroodiness. The results suggested that PRLpro2 could be a genetic marker in
      breeding against broodiness in chickens.

PMID- 15971520
TI  - Effects of dietary ratio of linoleic to linolenic acid on performance, antibody
      production, and in vitro lymphocyte proliferation in two strains of leghorn
      pullet chicks.
AB  - The effects of dietary ratio of linoleic acid to linolenic acid on performance,
      mitogenic lymphocyte proliferation, and antibody production were evaluated in
      Leghorn pullets during a rigorous vaccination program. Diets were supplemented
      with flaxseed and corn oil to achieve 4 dietary ratios of linoleic acid to
      linolenic acid [17:1 (control), 8:1, 4:1, or 2:1]. Each diet was fed to HyLine
      Brown or W-36 pullets from 1 d to 16 wk of age. Day-old pullets were randomly
      assigned to 8 replicate cages with 12 pullets per cage; the density was reduced
      to 8 pullets per cage at 11 wk of age. Dietary treatments did not affect body
      weight, feed consumption, or pullet mortality. At 12 wk of age, an interaction
      between diet and strain (P < or = 0.004) showed Hy-Line W-36 pullets fed the 2:1
      ratio had greater antibody production against Newcastle disease virus (NDV)
      vaccine than those fed diets with higher ratios. At wk 16, pullets fed ratios of
      4:1 and 2:1 had the greatest antibody production against NDV vaccine. Antibody
      production against infectious bursal disease virus (IBDV) vaccine was also
      increased (P < 0.04) by ratios of 4:1 (2.244 optical density; OD) or 2:1 (2.508
      OD) as compared with the control diet (1.576 OD). Hy-Line Brown pullets had
      greater antibody production against infectious bronchitis virus vaccine compared
      with Hy-Line W-36 pullets at 16 wk of age. These results indicate that feeding a
      reduced dietary ratio of linoleic to linolenic acid by adding flaxseed to the
      diets enhanced antibody response to NDV and IBDV vaccines without any negative
      effects on pullet performance.

PMID- 15971521
TI  - Versazyme supplementation of broiler diets improves market growth performance.
AB  - Day-old male broiler chicks were randomly assigned to 32 floor pens in a
      completely randomized block design and grown to 6 wk of age. Birds in experiment
      1 were fed 1 of 2 basal diets supplemented with or without a protease containing
      feed additive, Versazyme (VZ). The 4 treatments were 1) control (C), a corn
      soybean meal diet that contained 95% of amino acids recommended by NRC except for
      threonine and isoleucine; 2) C + 0.1% VZ (wt/wt) (C+) in the starter diet only;
      3) high (HP) amino acid diet, a corn-soybean meal diet with 100 to 105% of amino
      acid recommended by NRC except for threonine and isoleucine; and 4) HP + 0.1% VZ
      (wt/wt) (HP+) in starter diet only. Supplementing both diets with VZ improved BW
      and feed conversion ratio (FCR) at 21 d of age and BW at 42 d of age. Cumulative
      42-d FCR was only improved in birds fed the HP+ diet. Birds in experiment 2
      received the following treatments: 1) HP, 2) HP + 0.1% VZ batch A (wt/wt) (A) in
      starter diet only, and 3) HP + 0.1% VZ batch B (wt/wt) (B) in starter diet only.
      Enzyme supplementation improved 22-d BW and FCR. There was no significant
      difference in BW at 43 d of age. Both A and B improved overall FCR (1.758 and
      1.751 vs. 1.79 for A and B vs. HP, respectively). In conclusion, supplementation
      of starter broiler diets with VZ resulted in improved market growth performance.

PMID- 15971522
TI  - Effects of supplementing broiler breeder diets with organic selenium and
      polyunsaturated fatty acids on egg quality during storage.
AB  - We assessed the effects of supplementation of broiler breeder diets with
      polyunsaturated fatty acids (PUFA) and organic Se on hatching egg quality during
      storage. Broiler breeders (n = 352) were fed 1 of 4 diets: SO (soybean oil with
      no added Se), SO with Se (SO+Se), fish oil (FO), or FO and Se (FO+Se). Eggs from
      prepeak (23 wk) and peak production (27 wk) breeders were stored for 14 d under
      typical (15 degrees C, 78% RH) conditions. Eggs were analyzed for albumen Haugh
      units (HU) and pH, shell characteristics, egg component weight, Se content, and
      fatty acid (FA) profile. The efficiency of transfer of Se into the egg was
      greater in low Se treatments compared with in high Se treatments. The majority of
      Se from the low Se treatments was deposited in the yolk, whereas in high Se
      treatments, the Se was deposited evenly in the yolk and albumen. In the low Se
      treatments, the Se content of yolk and albumen was lower than in the high Se
      treatments and decreased as age increased. Albumen HU decreased with increased
      storage, although high Se treatments had greater HU compared with low Se
      treatments. Eggs from the FO treatment were smaller with thinner eggshells
      compared with the SO treatment, but addition of Se to the FO diets ameliorated
      some of these effects. The egg yolk FA profile from the SO+Se treatment was
      altered compared with that from the SO treatment, perhaps due to interactions
      between dietary PUFA and Se-dependent enzyme systems. Hatching egg quality during
      storage was affected by dietary PUFA and Se content, as well as broiler breeder
      age.

PMID- 15971523
TI  - Effects of enzyme supplementation on performance, nutrient digestibility,
      gastrointestinal morphology, and volatile fatty acid profiles in the hindgut of
      broilers fed wheat-based diets.
AB  - A growth trial and a metabolism trial were conducted as 2 experiments to
      investigate the effects of dietary enzyme supplementation (primarily xylanase and
      beta-glucanase) on performance, nutrient digestibility, intestinal morphology,
      digestive organ size, and volatile fatty acid profiles in the hindgut of broiler
      chickens fed wheat-based diets. The experimental diets in both trials consisted
      of a wheat-based control diet supplemented with 0, 200, 400, 600, 800, or 1,000
      mg/kg enzyme. Diets were given to the birds from d 7 to 42 of age. In the growth
      trial, enzyme supplementation improved performance of the broilers; daily gain
      and feed conversion increased linearly (P < 0.01) with increasing levels of
      enzyme supplementation. Enzyme inclusion decreased the size of the digestive
      organs and the gastrointestinal tract to some extent. The relative length of each
      intestinal segment decreased linearly (P < 0.05). The relative weight of the
      anterior intestine on d 21 and ileum on d 42 also decreased linearly (P < 0.01).
      On d 21 and 42, there were negative linear (P < 0.05) relationships between
      increasing enzyme supplementation and the relative weight of the liver and
      pancreas, respectively. Furthermore, there was a linear (P < 0.01) increase in
      total volatile fatty acid content in ileum on d 21 and in the cecum on d 21 and
      42. During each period of the metabolism trial, apparent crude protein
      digestibility increased linearly (P < 0.05), whereas no differences were detected
      (P > 0.05) in AME.

PMID- 15971524
TI  - Supplementation of zinc from organic or inorganic source improves performance and
      antioxidant status of heat-distressed quail.
AB  - Two sources of zinc [ZnSO4.H2O or ZnPicolinate (ZnPic)] supplementation were
      evaluated for their effects on performance, carcass weight, levels of
      malondialdehyde, and vitamins C, E, A in Japanese quail (Coturnix coturnix
      Japonica) exposed to high ambient temperature of 34 degrees C. The birds (n =
      360; 10-d-old) were randomly assigned to 12 treatment groups consisting of 3
      replicates of 10 birds each in a 2 x 2 x 3 factorial arrangement of treatments
      (temperatures, zinc sources, zinc levels). Birds were kept in wire cages in a
      temperature-controlled room at either 22 degrees C (thermoneutral) or 34 degrees
      C (heat stress) for 8 h/d (0900 to 1700 h) until the end of study, and fed a
      basal (control) diet or the basal diet supplemented with either 30 or 60 mg of Zn
      as ZnSO4 H2O or ZnPic/kg of diet. Heat exposure decreased (P = 0.001) live weight
      gain, feed intake, feed efficiency, and carcass weight when the basal diet was
      fed. A linear increase in feed intake (P = 0.01) and BW (P = 0.01), and
      improvement in feed efficiency (P = 0.01) and carcass weight (P < or = 0.05) were
      found in zinc-supplemented quail reared under heat-stress conditions. Serum
      vitamin C (P = 0.04), E (P = 0.05), and cholesterol (P = 0.01) concentrations
      increased linearly, whereas malondialdehyde concentrations decreased linearly (P
      = 0.02) as dietary zinc sulfate and ZnPic supplementation increased. An
      interaction between dietary zinc sources, temperature, and levels of
      supplementation (P < or = 0.05) for these parameters was detected. Serum vitamins
      C, E, and A concentrations were not different in supplemented birds reared at
      thermoneutral temperature. Supplementation with zinc improved carcass weight and
      antioxidant status of birds, and the effects of ZnPic were relatively greater
      than those of ZnSO4.H2O in heat-stressed quail. Results of the present study
      suggest that supplementation with ZnPic could be considered to be more protective
      than ZnSO4.H2O by reducing the negative effects of oxidative stress induced by
      heat stress in quail.

PMID- 15971525
TI  - Effects of dietary supplementation with copper sulfate or tribasic copper
      chloride on broiler performance, relative copper bioavailability, and oxidation
      stability of vitamin E in feed.
AB  - An experiment was conducted using a total of 420, 1-d-old, Arbor Acres commercial
      male chicks to compare copper sulfate and tribasic copper chloride (TBCC) as
      sources of supplemental copper for broilers. Chicks were randomly allotted to 1
      of 7 treatments for 6 replicates of 10 birds each and were fed a basal corn
      soybean meal diet (11.45 mg/kg copper) supplemented with 0, 150, 300, or 450
      mg/kg copper from copper sulfate or TBCC for 21 d. Chicks fed 450 mg/kg copper as
      copper sulfate had lower (P < 0.01) average daily feed intake and average daily
      gain than those consuming other diets. Feeding supplemental copper increased
      linearly (P < 0.0001) liver copper concentrations regardless of copper source.
      The slopes of regressions of log10 liver copper on different independent
      variables used in regressions differ (P < 0.05) between the 2 copper sources.
      Linear regression over nonzero dietary levels of log10 transformed liver copper
      concentration on added copper intake resulted in a slope ratio estimate of 109.0
      +/- 3.4% (with a 95% confidence interval from 102.2 to 115.8) for bioavailability
      of copper from TBCC compared with 100 for that in copper sulfate. When the feeds
      were stored at room temperature for 10 or 21 d, the vitamin E content in the feed
      fortified with 300 mg/kg copper as TBCC was higher (P < 0.01) than that in the
      feed added with 300 mg/kg copper as CuSO4. The vitamin E contents in liver and
      plasma of broilers given TBCC were also higher (P < 0.01) than those of birds fed
      copper sulfate. The results from this study indicate that TBCC is a safer product
      and more available to broilers than copper sulfate, and it is chemically less
      active than copper sulfate in promoting the oxidation of vitamin E in feed.

PMID- 15971526
TI  - Effects of beta-mannanase in corn-soy diets on commercial leghorns in second
      cycle hens.
AB  - beta-Mannanase (Hemicell) is a unique enzyme-based feed ingredient that can
      hydrolyze beta-mannan, an antinutritional fiber in feed. Because soybean meal
      contains beta-mannan and its derivatives, addition of beta-mannanase may improve
      soybean-meal utilization. The purpose of this study was to evaluate the effect of
      beta-mannanase on performance of commercial Leghorns fed corn-soybean meal based
      diets. In this experiment, 3 diets were formulated. The metabolizable energy
      content for diet 1 (high-energy diet) was 2,951 kcal/kg, which was 120 kcal/kg
      higher than diet 2 (low-energy diet supplemented with beta-mannanase) and diet 3
      (low-energy diet without beta-mannanase). Hy-Line W-36 hens (n = 720, 98 wk old)
      were randomly divided into 3 dietary treatments (16 replicates of 15 hens per
      treatment). The trial lasted for 12 wk. Overall average feed conversion of hens
      fed the low-energy diet supplemented with beta-mannanase was similar to that of
      hens fed the high-energy diet, and both were significantly lower than that of
      hens fed the low-energy diet without beta-mannanase. There were no significant
      differences in overall average egg production and egg mass among 3 dietary
      treatments for the 12-wk period. However, the addition of beta-mannanase
      significantly increased average egg production and egg mass of hens fed the low
      energy diet from wk 5 to 8. There were no significant differences in feed intake,
      egg specific gravity, egg weight, mortality, body weight, and body weight
      variability among the 3 dietary treatments. beta-Mannanase supplementation
      improved energy utilization of corn-soybean layer diets and has potential to
      reduce the cost of practical laying hen diets containing beta-mannan.

PMID- 15971527
TI  - Comparison of inorganic and organic selenium sources for broilers.
AB  - An experiment was conducted to compare the effects of organic and inorganic
      sources of Se on growth performance, carcass traits, breast and plasma Se
      concentrations, and plasma glutathione peroxidase (pGPX3) activity in broilers.
      Broiler chicks were sexed on d 0 and within sex, randomly allotted to dietary
      treatment. Average initial and final BW of the broilers were 47 and 2,684 g, and
      the experiment lasted 49 d. A 3-phase feeding program similar to industry
      recommendations was used, and the basal diets for each phase were corn-soybean
      meal based. For each growth phase, the basal diet was supplemented with 0
      (control) or 0.30 ppm Se from sodium selenite (SS) or Se-enriched yeast (SY).
      Each treatment was replicated 7 times (4 pens of males and 3 pens of females)
      with 50 male or 55 female broilers per replicate. Daily gain, feed intake,
      gain:feed, eviscerated and chill weights, carcass yield, breast weight, and
      moisture loss from the breast were not affected (P > 0.05) by Se supplementation.
      Dietary supplementation with SY increased (P < 0.05) muscle and plasma Se
      concentrations compared with broilers fed the control diet or the diet with SS.
      Plasma GPX3 activity was not affected (P > 0.05) by Se source or concentration.
      The results from this experiment indicate that organic Se increases tissue Se
      concentration, but it does not affect growth performance, carcass traits, or
      pGPX3 activity compared with inorganic Se.

PMID- 15971528
TI  - Metabolic response of the gastrointestinal tract of turkeys to diets with
      different levels of mannan-oligosaccharide.
AB  - Different levels of dietary mannan-oligosaccharide (MOS) administered for 16 wk
      to commercial male turkeys were evaluated for their efficacy on performance and
      on microbial activity in the digestive tract. The following levels of MOS were
      used in a diet: low (0.1% during the entire study), medium (0.4 and 0.2% in the
      first and second 8-wk periods, respectively), and high (1.0 and 0.4% in the first
      and second 8-wk periods, respectively). After 16 wk of experimental feeding, the
      diet intake was similar in all groups examined, whereas the live BW was
      significantly higher in groups with medium and high levels of MOS compared with
      the control group and birds fed a diet containing a low level of mannan. The pH
      of ileal and cecal contents were unaffected by dietary treatments. The highest
      ammonia concentration in the cecal digesta was associated with a low dose of
      mannan in a diet, and the concentration was reduced to the control level when
      both higher doses of MOS were used. Bacterial enzyme activity remained unaffected
      by experimental treatments. The concentration of short-chain fatty acids in the
      ceca decreased with increasing amounts of MOS in a diet, especially in the case
      of acetate. Dietary MOS did not significantly affect the cecal populations of
      Bifidobacterium and Lactobacillus. The population of cecal Escherichia coli was
      decreased, especially by the medium and high experimental treatments.

PMID- 15971529
TI  - The interactive effects of Eimeria acervulina infection and phytase for broiler
      chicks.
AB  - An experiment was conducted to determine the interactive effects of Eimeria
      acervulina infection and phytase in male broiler chicks. Chicks were standardized
      from 0 to 4 d posthatching, and the assay period was 5 to 15 d. Treatments were
      replicated with 6 pens of 5 chicks each. The initial and final BW were 67 and 363
      g. A corn-soybean meal diet formulated to provide 1.26% total Lys and 3,200 kcal
      of ME/kg was used, and it was adequate in all other nutrients except Ca and
      nonphytate P (NPP) when appropriate. The treatments were in a 2 x 2 x 2 factorial
      arrangement: adequate Ca and NPP (1.0% Ca and 0.45% NPP) or inadequate Ca and NPP
      (0.80% Ca and 0.25% NPP), 0 or 600 phytase units/kg of diet, and uninfected or
      infected with 400,000 E. acervulina oocysts on d 0, 3, and 6 of the experiment.
      Daily gain, average daily feed intake, and gain:feed (GF) were reduced (P < 0.01)
      by the coccidial infection and the reduction in Ca and NPP. Phytase addition
      increased (P < 0.02) average daily gain and average daily feed intake, regardless
      of the Ca and NPP contents of the diet or the presence of coccidiosis. The GF was
      increased by phytase but only in uninfected chicks (phytase x coccidiosis, P <
      0.02). Toe and tibia ash percentages were decreased (P < 0.01) in chicks fed
      diets deficient in Ca and NPP, but tibia ash was decreased more by Ca and NPP in
      healthy chicks than in infected chicks (coccidiosis x Ca and NPP, P < 0.02).
      Phytase increased (P < 0.02) toe and tibia ash but only in diets deficient in Ca
      and NPP (phytase x Ca and NPP, P < 0.01). Phytase increased toe ash percentage of
      healthy chicks fed diets deficient in Ca and NPP, but it had less of an effect in
      infected chicks fed diets deficient in Ca and NPP (coccidiosis x Ca and NPP x
      phytase, P < 0.08). Also, phytase was less effective in increasing tibia ash
      percentage in coccidiosis-infected chicks than in uninfected chicks (phytase x
      coccidiosis, P < 0.02). These data indicate that phytase is effective in the
      presence of a coccidial infection, but based on GF and tibia ash percentage, it
      may not be as effective as in uninfected chicks. Also, phytase increased average
      daily gain and average daily feed intake in uninfected chicks fed diets
      formulated to be adequate (or in excess) in all nutrients for male broiler
      chicks.

PMID- 15971530
TI  - Effect of eggshell temperature during incubation on embryo development,
      hatchability, and posthatch development.
AB  - An experiment was conducted to study the effects of different eggshell
      temperature (EST) profiles during incubation on embryo mortality, hatchability,
      and embryo development. Furthermore, chicks from different EST profiles were
      reared under low and high housing temperatures to investigate subsequent
      posthatch growth and rectal temperature. Two batches of eggs were used in this
      experiment. Hatching eggs were subjected to 36.7 or 37.8 degrees C EST during the
      first week, to 37.8 degrees C EST during the second week, and to 37.8 or 38.9
      degrees C EST during the third week of incubation. Posthatch housing temperature
      decreased from 35 degrees C at d 1 to 30 degrees C at d 7 (high) or decreased
      from 30 degrees C at d 1 to 25 degrees C at d 7 (low). The difference between
      machine temperature and EST (DT) was used to illustrate the effect of EST on heat
      production during incubation. DT differed per batch, and was smallest when eggs
      were incubated at 36.7 degrees C instead of 37.8 degrees C during wk 1. High EST
      during wk 3 of incubation (38.9 degrees C instead of 37.8 degrees C) reduced DT
      only in batch 2. Embryo development was most retarded in eggs incubated at 36.7
      degrees C EST compared with at 37.8 degrees C during the first week of
      incubation. However, highest hatchability and embryo development were always
      found when EST was maintained at 37.8 degrees C constantly throughout incubation.
      Chicks that hatched from eggs incubated at low EST during wk 1 of incubation had
      lower rectal temperature after hatching, especially under low housing
      temperatures, and this effect lasted until 7 d posthatch in batch 1. The highest
      rectal temperatures were always found in chicks incubated at 37.8 degrees C EST
      constantly throughout incubation. Eggs and chicks from different batches require
      different environmental conditions for optimal embryo development, hatchability,
      and posthatch growth. Rearing temperature and incubation conditions affect the
      ability of young chicks to maintain their rectal temperature during the first
      week posthatch.

PMID- 15971531
TI  - In vitro effects of deoxynivalenol on electrical properties of intestinal mucosa
      of laying hens.
AB  - Deoxynivalenol (DON) is common in European cereal grains, and of all the
      trichothecenes, poses the greatest problems to animal health. The present study
      investigated the effects of DON on electrophysiological parameters in laying
      hens' jejunum mounted in Ussing chambers. In vitro studies were performed to
      measure the effects of different luminal concentrations of DON (0.5, 1, 5, and 10
      microg/mL) on the transmural potential difference, electrical tissue resistance,
      and electrogenic ion flux rates (short-circuit current, Isc) across the isolated
      gut mucosa. Deoxynivalenol did not alter (P > 0.05) the transmural potential
      difference. Resistance was higher (P < 0.05) in the tissues exposed to DON
      compared with basal values. Deoxynivalenol caused a dose-dependent decrease in
      Isc (P < 0.05). To investigate the mechanism of action of DON, amiloride (a
      specific inhibitor for Na+ transport) was added after incubation of the tissue
      with DON. Amiloride did not decrease (P > 0.05) Isc under these conditions. This
      may indicate that DON inhibited the Na+ transport before addition of amiloride,
      which did not then show further inhibitory effects. The addition of D-glucose (5
      mmol/L) on the luminal side of the isolated mucosa increased (P < 0.05) Isc, and
      this effect was reversed by phlorizin (a specific inhibitor of sodium/glucose
      transporter 1), indicating that the glucose-induced Isc increase may be due to
      Na+-D-glucose cotransport. In our study, DON decreased (P < 0.05) the glucose
      induced Isc in a similar way to phlorizin. The remarkable similarity between the
      effects of phlorizin and DON on electrical properties seemed to be consistent
      with their common ability to inhibit Na+-D-glucose cotransport. In conclusion,
      DON decreased the Isc via inhibition of Na+ transport. The effect on intestinal
      electrical properties was similar to that of phlorizin after addition of glucose,
      suggesting that DON may inhibit Na+-D-glucose cotransport. The inhibition of Na+
      transport and Na+-D-glucose cotransport are important mechanisms of DON toxicity
      in the intestine of laying hens.

PMID- 15971532
TI  - Effects of luminal deoxynivalenol and L-proline on electrophysiological
      parameters in the jejunums of laying hens.
AB  - Most amino acids are cotransported with sodium. Deoxynivalenol (DON) decreases
      glucose absorption in the chicken small intestine in vivo and in vitro, and this
      effect is apparently mediated by the inhibition of the sodium D-glucose
      cotransporter. DON could selectively modulate the activities of other intestinal
      transporters. In order to assess this hypothesis, a study was conducted to
      characterize the in vitro effects of DON in the presence of mucosal amino acids,
      using L-proline as a model, on the electrophysiological parameters in the
      jejunums of laying hens. L-Proline (mucosal concentration of 1 mmol/L) was added
      to a stripped proximal part of jejunum sheets mounted in Ussing chambers in
      Ringer buffer, and the electrical properties were measured. The transmural
      potential difference (PD) was nearly constant between the treatments. The tissue
      resistance (Rt) was higher (P < 0.05) in the tissues exposed to DON compared with
      basal values and the values after addition of L-proline. Addition of L-proline on
      the luminal side of the isolated mucosa increased (P < 0.05) the short circuit
      current (Isc), and it decreased (P < 0.05) after addition of DON, indicating that
      the proline-induced Isc was altered by DON. The addition of proline after
      incubation of the tissues with DON had no effect (P > 0.05) on PD or Rt. Proline
      did not increase the Isc under these conditions. DON decreased (P < 0.1) the Isc
      after addition of proline, indicating that DON inhibited the Na+-amino acid co
      transport. We concluded from the present study that the amino acid cotransporter
      activity appears to be highly sensitive to DON suppression.

PMID- 15971533
TI  - Compromised liver mitochondrial function and complex activity in low feed
      efficient broilers are associated with higher oxidative stress and differential
      protein expression.
AB  - Variations in broiler growth and efficiency have been explained in part by
      differences in mitochondrial function and biochemistry in broilers. To further
      our knowledge in this regard, 2 experiments were carried out to determine the
      relationships of a) mitochondrial function and activities of various electron
      transport chain (ETC) complexes; b) production of H2O2, a reactive oxygen species
      (ROS), and its association with protein oxidation; and c) mitochondrial protein
      expression in liver of a single line male broilers with low or high feed
      efficiency (FE, n = 5 to 8 per group). Mitochondrial function and complex
      activities were measured polarographically and spectrophotometrically,
      respectively. H2O2 was measured fluorimetrically, whereas oxidized protein
      (carbonyls) and specific mitochondrial proteins were analyzed using Western
      blots. Mitochondrial function (ETC coupling) and activities of ETC complexes (I,
      II, III, and IV) were higher in high FE compared with low FE broilers. H2O2 and
      protein carbonyls were higher in the livers of low FE broilers than in high FE
      broilers. Whereas the expression of 4 immunoreactive proteins [NAD3 (complex I),
      subunit VII (complex III), cytochrome c oxidase subunits (COX) II, and COX IVb
      (complex IV)] were higher in low FE liver mitochondria and 2 proteins [subunit 70
      (complex II) and a-ATP synthase (complex V)] were higher in high FE birds, there
      were no differences between groups in the expression of 18 other mitochondrial
      proteins. In conclusion, increases in oxidative stress in low FE broilers were
      caused by or may contribute to differences in mitochondrial function (ETC
      coupling and complex activities) or the differential expression of steady-state
      levels of some mitochondrial proteins in the liver. Understanding the role of
      oxidative stress in Low FE broilers will provide clues in understanding the
      cellular basis of feed efficiency.

PMID- 15971534
TI  - Thyroid hormone and prolactin profiles in male and female turkeys following
      photostimulation.
AB  - The turkey hen, a photosensitive bird, will become photorefractory (PR) during
      the reproductive cycle and will cease laying despite a stimulatory day length.
      This response is thought to be "programmed" by hormonal events early in the
      reproductive cycle. The turkey tom, in contrast, produces semen for extended
      periods and has not been shown to exhibit PR. We compared hormone profiles
      following photostimulation of hens and toms to assess differences that might
      program one, but not the other, for PR. We photostimulated with 16 h light per
      day and measured plasma prolactin (PRL), thyroxine (T4), and triiodothyronine
      (T3) weekly for 12 wk, and again at 16 and 22 wk. Hens were fed ad libitum, and
      toms were moderately feed-restricted. Results showed increasing PRL levels
      following photostimulation in hens, with peak levels occurring at about the time
      of peak egg production, and declining thereafter. Toms maintained significantly
      lower concentrations of PRL (P < 0.0001) than hens after 2 wk of
      photostimulation. A highly significant sex by time interaction in plasma T3
      levels was observed due to extreme fluctuations in males. Similar, often
      reciprocal, fluctuations in mean T4 concentrations also occurred in males. We
      recycled the toms and repeated blood collections under identical conditions, but
      with ad libitum feeding to determine if feed restriction may have produced these
      unusual results. This study revealed an initial significant decline in plasma T3
      levels and an increase in T4 levels immediately following photostimulation, and
      then steady (T4) or slowly rising (T3) levels through 12 wk photostimulation. We
      conclude that PRL profiles of toms and hens differ markedly during the
      reproductive cycle, lending support to the suggestion that rising PRL may mediate
      the onset of PR. Further study is needed to determine if the low plasma T3 levels
      in males may be related to delayed PR. The extreme fluctuations in plasma T3 and
      T4 levels of toms receiving relatively mild feed restriction suggest a need for
      further study of the metabolic effects of feed restriction in turkeys.

PMID- 15971535
TI  - Intestinal D-glucose and L-alanine transport in Japanese quail (Coturnix
      coturnix).
AB  - The mechanisms involved in D-glucose and amino acid transport in the intestine of
      birds are still not clear. In chickens, D-glucose and amino acid absorption
      occurs via carrier-mediated transport, but in wild birds a passive paracellular
      mechanism seems to be the predominant pathway. The purpose of this work was to
      determine the existence of carrier-mediated sodium cotransport of D-glucose and L
      alanine in the small intestine of Japanese quail (Coturnix coturnix), a
      granivorous bird. Intestinal transport was determined by changes in the short
      circuit current (Isc), proportional to ion transmembrane flux, in the middle
      segment of the intestine of Japanese quail with a Ussing chamber. D-Glucose
      produced an increase of the Isc, and this effect was reverted by phloridzin,
      indicating the presence of a D-glucose transport mediated by the sodium/glucose
      cotranspoter 1. Addition of L-alanine also produced an increase of the Isc. We
      concluded that there is carrier-mediated cotransport of D-glucose and L-alanine
      with sodium in the small intestine of the Japanese quail.

PMID- 15971536
TI  - Early postmortem carcass trim effects on the tenderness of broiler breast
      fillets.
AB  - Broiler carcasses are often trimmed during evisceration to remove damaged areas
      of the carcass. Because deboning before rigor mortis development can toughen
      meat, trimming during evisceration may toughen the meat. This study evaluated the
      effects of trimming on the tenderness of broiler breast meat. To evaluate the
      effect of wing removal on tenderness, breast halves from 2 flocks were collected
      after chilling at a commercial plant. One-third were untrimmed controls, one
      third had small amounts of breast meat removed with wing (WMin), and one-third
      had large amounts of breast meat removed with wing (Wmax). Salvage fillets from
      the 2 flocks were also collected from the salvage table of the plant. Carcasses
      were also processed to evaluate the effect of breast blister trimming that
      removed a superficial amount of muscle tissue, half of which had breast blister
      trims, and half did not. All front halves or carcasses were aged until 24 h
      postmortem and deboned. Salvage fillets were held refrigerated until 24 h
      postmortem. Fillets were cooked and then sheared in 2 locations on the fillet,
      upper and lower, to determine if tenderness was more affected at areas close to
      the trim. Carcasses with wing trims had significantly higher shear values
      compared with the control, and shear values from the upper portion of the fillets
      from the WMax and WMin (nearer the trim) were significantly greater than for the
      lower portion. Location, however, did not affect shear values in the control
      carcasses. This finding indicated that tenderness of the areas nearest the trim
      might be affected more by the trim process. Salvage table deboning significantly
      increased shear values throughout the fillet. There was no significant difference
      in shear value due to breast blister trimming. The results of this study suggest
      that trimming carcasses by wing or breast fillet removal results in decreased
      meat tenderness.

PMID- 15971537
TI  - The effect of electron beam irradiation on the survival of Salmonella enterica
      serovar typhimurium and psychrotrophic bacteria on raw chicken breasts stored at
      four degrees celsius for fourteen days.
AB  - The effect of high-energy electron beam irradiation on the survival of Salmonella
      enterica serovar Typhimurium and psychrotrophic bacteria on commercial chicken
      breast meat was evaluated. Fresh chicken breast meat was purchased from a local
      poultry processor, inoculated with 8 log10 cfu/mL Salmonella, packaged in
      Styrofoam trays and over wrapped with a polyvinyl chloride film, and subjected to
      0, 1, 2, or 3 kGy of irradiation. The packaged samples were stored at 4 degrees C
      and analyzed for Salmonella Typhimurium and psychrotrophic organisms at 0, 2, 4,
      6, 8, 10, 12, and 14 d of storage. Direct plating and enrichment methods were
      used for S. Typhimurium analyses. The direct plating method revealed a 4 log
      reduction in Salmonella for chicken breasts inoculated and treated with 1, 2, or
      3 kGy of irradiation. Psychrotrophic counts were conducted at 7 degrees C for 10
      d and 25 degrees C for 5 d to determine the effect of incubation methods on the
      recovery of psychrotrophic organisms. The enrichment method resulted in the
      repair of injured Salmonella cells and an elevated Salmonella Typhimurium count
      for all irradiation dosages when compared with data reported for the direct
      plating method. In general, psychrotrophic counts increased as storage time
      increased. However, psychrotrophic counts decreased (P < 0.05) as the irradiation
      dosage increased.

PMID- 15971538
TI  - Adsorption of aflatoxin B1 on montmorillonite.
AB  - The isothermal adsorption and the adsorptive mechanism of aflatoxin B1 (AFB1) on
      calcium montmorillonite (Mont) were studied in vitro trials. The maximum amounts
      of AFB1 on Mont in aqueous solution at 2 and pH 8 were 613.5 and 628.9 microg of
      AFB1 /g of Mont, respectively. The structure of AFB1-Mont was measured by x-ray
      diffraction and infrared absorption spectrum. The results suggested that the
      mechanism of AFB1 on Mont was AFB1 sorbed onto the edge of Mont by a double
      hydrogen bond, and AFB1 molecules did not penetrate into the interlayer area of
      Mont. The Mont, when added to the diet of broiler chicken at 0.5%, significantly
      diminished the adverse effects of feeding 200 microg of AFB1 /kg of feed. And the
      concentrations of Ca, P, Cu, Fe, Zn in the broiler bones were not affected by
      AFB1 and Mont, but the concentrations of Mn, Pb, and F were decreased by Mont.

PMID- 15971539
TI  - Growth responses of male broilers subjected to increasing air velocities at high
      ambient temperatures and a high dew point.
AB  - This study examined live performance responses of male broilers to increasing air
      velocity of 120 and 180 m/min reared under high cyclic temperatures (25-35-25
      degrees C) with a 23 degrees C dew point from 21 to 49 d. Birds were reared in an
      environmental facility containing 2 wind tunnels (4 pens/tunnel) and 6 floor pens
      (control). At 21 d, 53 birds were placed in each pen of the wind tunnels and
      control group, respectively, and growth performance was determined weekly.
      Increasing air velocity from 120 to 180 m/min improved BW and BW gain from 29 to
      35, 36 to 42, and 43 to 49 d of age leading to a cumulative advantage of 287 g in
      BW gain and a 10-point difference in feed conversion from 21 to 49 d of age.
      Subjecting birds to air velocity improved growth rate, feed consumption, and feed
      conversion at each weekly interval from 28 to 49 d over the control birds. These
      results indicate that male broilers approximating 2.0 to 3.0 kg respond to an air
      velocity of 180 m/min when exposed to high cyclic temperatures.

PMID- 15971540
TI  - Pre- and postnatal conditioning induced thermotolerance on body weight,
      physiological responses and relative asymmetry of broilers originating from young
      and old breeder flocks.
AB  - The present experiment was conducted to examine the effects of pre- and postnatal
      conditioning to induce thermotolerance in broilers hatching from eggs orginating
      from younger and older breeder flocks. From each flock, 500 eggs were randomly
      divided into 2 groups and incubated at standard (SIT) and high (HIT)
      temperatures. At hatch, chicks were allotted to 36 floor pens. At 5 d of age 3
      pens per parent age per incubation temperature were heat conditioned (C) for 24
      h. At 21 d of age, 3 pens per parent age per incubation temperature were kept
      under standard (S) rearing temperatures, whereas the remaining broilers
      (including C) were moved to a heated room (H). Thus, there were 3 groups from 21
      to 49 d including S, H, and C+H. The results indicated that to incubate eggs from
      younger parents at HIT before conditioning at 5 d may reduce deleterious effects
      of heat stress on body weight at slaughter age. However, HIT temperature
      decreased slaughter weight of broilers from older parents regardless of rearing
      temperature. Although conditioning did not prevent increments in rectal
      temperatures of broilers after 1 wk of heat stress (28 d), adaptation occurred
      thereafter for broilers from younger parents but not for broilers from older
      parents. Incubation temperature had no effect on plasma glucose, creatine kinase,
      uric acid, or triiodotryronine (T3) levels at d 21. There were no differences at
      22, 25, or 28 d for T3 concentrations between the H and C+H groups. Overall
      relative asymmetry was not influenced by treatments on d 49. The results suggest
      that although pre- and postnatal conditioning may help broilers cope with heat
      stress, age of parent plays a major role in the ability of broilers to
      thermoregulate. This is especially the case for broilers originating from younger
      parents.

PMID- 15971541
TI  - Sterility failure analysis.

PMID- 15971542
TI  - Choosing the appropriate membrane filter--test requirements.

PMID- 15971543
TI  - Optimization of the drug solution preparation process for a production-scale
      crossflow ultrafiltration system.
AB  - This article describes a new approach to optimizing the drug solution preparation
      process for a production-scale crossflow ultrafiltration system. Equations were
      proposed to predict the concentration of the active ingredient and the volume of
      drug solution in the crossflow ultrafiltration process. These equations take into
      account the residual water remaining in the process line after the set-up of the
      ultrafiltration system, the residual drug solution remaining in the process line
      after ultrafiltration, and the residual Water for Injection (WFI) remaining in
      the process line after WFI rinsing. Because the residual water or residual drug
      solution varies slightly for each type of production, it was convenient to define
      them as preparation parameters. Using the proposed equations, testing was
      performed during early production in order to collect data on the crossflow
      ultrafiltration process, and the preparation parameters were then optimized. The
      concentration of the active ingredient and the weight of the drug solution (which
      was converted to the drug solution volume using its specific gravity) were
      calculated accurately with the optimized preparation parameter using the proposed
      equations. These results indicate that the proposed equations and method of
      establishing the preparation parameters are useful for a production-scale
      crossflow ultrafiltration system.

PMID- 15971544
TI  - Aseptic processing contamination case studies and the pharmaceutical quality
      system.
AB  - This paper summarizes parenteral drug contamination case studies presented at
      industry conferences and a Food and Drug Administration advisory committee
      meeting in the period of 2000-2004. CGMP deficiencies associated with each
      contamination event are discussed. The key role of a well-functioning quality
      system in contamination prevention is emphasized.

PMID- 15971545
TI  - Assessing parallelism prior to determining relative potency.
AB  - In the course of preparing a revision to Chapter (111) of the U.S. Pharmacopeia,
      the revision committee came to a unanimous agreement that the method for
      assessing parallelism that is currently presented in (111) and in the European
      Pharmacopeia's Chapter 5.3 is flawed and should be replaced. The symptoms are
      that perfectly acceptable assay results may fail due to good precision and that
      obviously faulty assay results may pass due to poor precision. The flaw is that
      the wrong statistical technique has been used. We propose an alternative approach
      based on the equivalence testing paradigm that does not have these shortcomings.
      Equivalence testing requires the establishment of equivalence limits. Specific
      approaches for establishing equivalence limits are discussed.

PMID- 15971546
TI  - Determination of mass and heat transfer parameters during freeze-drying cycles of
      pharmaceutical products.
AB  - The principal aim of this study was to evaluate the water vapour mass transfer
      resistance of the dried layer and the vial heat transfer coefficient values of a
      pharmaceutical product during the primary drying period. First, overall vial heat
      transfer coefficient values, Kv, were determined by a gravimetric method based on
      pure ice sublimation experiments. Thus, it was possible to set up a map of the
      total heat flux received by each vial throughout the plate surface of our pilot
      scale freeze-dryer. Important heterogeneities were observed for the vials placed
      at the plate edges and for the vials placed at the center of the plate. As well,
      the same gravimetric method was also used to precisely determine the influence of
      main lyophilization operating parameters (shelf temperature and gas total
      pressure) or the vial types and sizes on these overall heat transfer coefficient
      values. A semi-empirical relationship as a function of total gas pressure was
      proposed. The transient method by pressure rise analysis (PRA method) after
      interrupting the water vapour flow between the sublimation chamber and the
      condenser, previously set up and validated in our laboratory, was then
      extensively used with an amorphous BSA-based formulation to identify the dried
      layer mass transfer resistance values, Rp, the ice front temperature, and the
      total heat transfer coefficient values, Kv, with or without annealing treatment.
      It was proved that this method gave accurate and coherent data only during the
      first half of the sublimation period when the totality of the vials of the set
      was still sublimating. Thus, this rapid method allowed estimation of, on line and
      in situ, the sublimation front temperature and the characterization of the
      morphology and structure of the freeze-dried layer, all along the first part of
      the sublimation period. The estimated sublimation temperatures shown by the PRA
      model were about 2 degrees C lower than the experimental values obtained using
      thermocouples inserted inside the vial, in accordance with previous data given by
      this method for similar freeze-drying conditions. As well, by using this method
      we could confirm the homogenization of the dried layer porous structure by
      annealing treatment after the freezing step. Furthermore, frozen matrix structure
      analysis (mean pore diameter) using optical microscopy and mass transfer
      modelling of water vapour by molecular diffusion (Knudsen regime) allowed, in
      some cases, to predict the experimental values of this overall mass transfer
      resistance directly related to the freeze-dried cake permeability.

PMID- 15971547
TI  - Incidence and aetiology of oral clefts: a review.
AB  - Craniofacial anomalies, most especially cleft lip and palate, are major human
      birth deformities with a world wide incidence of 1 in 700 and associated
      substantial clinical and psychosocial impact. Wide ranges of studies in
      developmental biology have shown that both genetics and environmental factors are
      involved in the etiology of oral clefts. However, genetics of cleft lip alone or
      accompanied by cleft palate, are different from those of isolated cleft palate.
      The prevention of oral clefts is not possible without knowing the precise
      etiology. Genetic counseling can now identify high risk families; the clefts
      themselves may be visible at 20 weeks gestation, but beyond early identification,
      we can only look into the future on the possibility of preventing oral clefts.
      This article reviews the available literature on the gene-environment
      contributions to nonsyndromic forms of clefting and their implication for
      possible preventive measures.

PMID- 15971548
TI  - Complement factors and circulating immune complexes in children with urinary
      schistosomiasis and asymptomatic malaria.
AB  - Serum concentrations of circulating immune complexes (CIC), complement factors
      (Factor B, C4, C8) and complement activities (CH50 and AH50) were determined in
      Nigerian school children having urinary schistosomiasis with or without
      symptomatic malaria by polyethylene glycol precipitation method, single radial
      immunodiffusion and total haemolytic activities respectively. One hundred and
      forty-seven children were recruited from St. John's Primary School, Mokola,
      Ibadan, Nigeria.RP ovale only, mixed infection of P. ovale with P. falciparum or
      mixed infection of P. malariae with P. falciparum were found in subjects with
      asymptomatic malaria without urinary schistosomiasis (M-USS) but P. malariae or
      P. falciparum was found in subjects with co-infection of urinary schistosomiasis
      and asymptomatic malaria (M + USS). Mean value of C4 concentration was
      significantly reduced in M - USS subjects or subjects having both USS and
      asymptomatic malaria (M + USS) compared with non-infected controls. Serum
      concentration of Factor B(FB) was significantly reduced while AH50 was
      significantly increased in urinary schisosomiasis subjects without malaria (USS
      M) compared with M-USS subjects or the controls. These observations implied that
      complement system in USS-M subjects is activated predominantly via alternative
      pathway (APW) while complement system is activated via classical pathway (CPW) in
      M-USS or M+USS subjects. The switch of complement activation pathway from
      alternative type in USS-M subjects to classical type in M-USS subjects may
      explain the lower malaria parasite densities often found in children harbouring
      Schistosoma haematobium parasites.

PMID- 15971549
TI  - Financial cost of treating Nigerian in-patients with schizophrenia.
AB  - Fifty seven each ofhospitalised schizophrenic patients (fulfilled diagnostic
      criteria for research version of I.C.D. 10) and diabetic patients respectively,
      matched for age and sex, were followed up from admission to discharge (July 1997 
      December 1997). B.P.R.S. was used to measure the severity of psychopathology at
      admission and discharge for the former, while the levels of blood glucose at
      admission and discharge were assessed for the latter. Also, interviewed during
      the study were 374 relatives comprising 102 and 272 relatives of schizophrenic
      and diabetic patients respectively. Weekly assessments of cost of treatment were
      done from admission to discharge using the proforma which took cognisance of
      aspects of direct and indirect costs for patients and relatives of both groups.
      Schizophrenic patients had a poorer employment record (P = 0.000), more diabetic
      patients were married (P = 0.000), relatives shouldered the financial burden of
      care of more schizophrenic patients (P = 0.000), more schizophrenic patients
      travelled over an average of 122 km to reach the hospital whereas diabetic
      patients travelled averagely 19.8 km (P = 0.000) and the mean duration of
      admission for schizophrenic patients was significantly longer (P = 0.000). The
      mean monthly income for diabetic patients was significantly higher than for
      schizophrenic patients (P = 0.000), and the mean direct cost for schizophrenia
      per admission 9882.00 Naira was significantly higher than that of diabetes
      mellitus 7892.00 Naira (P = 0.000). The mean indirect cost for schizophrenic
      patients per admission which is 3604.00 Naira did not differ significantly from
      that of diabetic patients of 1488.00 Naira (P = 0.288). The mean total cost of
      schizophrenia per admission--is 11,337.00 Naira and was significantly higher than
      for diabetes 8571.00 Naira (P = 0.000). However, the mean direct cost per week
      for diabetes mellitus 4494.00 Naira was significantly higher than for
      schizophrenia 1011.00 Naira (P = 0.00). The mean indirect cost for diabetes
      mellitus per week 406.00 Naira did not differ significantly from that
      ofschizophrenia 168.00 Naira (P = 0.602). The mean total cost of diabetes
      mellitus per week 4910.00 Naira was significantly higher than for schizophrenia
      1235.00 Naira (P = 0.000). Cost of medication ranked highest in all items of cost
      for both the schizophrenic and diabetic cohorts. The implications of the findings
      on clinical practice in Nigeria and our current socio-economic scenario
      (especially with regard to schizophrenic patients and their families) are
      discussed. The need to reinforce the socio-economic support from government and
      the larger society for schizophrenic patients and their families is highlighted.

PMID- 15971550
TI  - Knowledge about HIV/AIDS and sexual practice among University of Ibadan Students.
AB  - This study assessed the knowledge about HIV/AIDS and sexual practice of
      University students in Ibadan, Nigeria. Two hundred and seventeen students from
      the University of Ibadan were randomly selected in 2001 from the College of
      Medicine,Daculties of Arts and Law and completed a questionnaire. The ages of the
      students ranged from 16-23 with a mean of 19.05 years; 98.2% of the students
      reported blood transfusion as a major route of transmission of HIV/ AIDS. This
      was followed by use of unsterilized needle (97.2%) and unprotected sexual
      intercourse (93.5%). The heterosexual route of transmission was rated third.
      Sexual practice of the students showed 29% were sexually active. 91.2% considered
      HIV/AIDS a serious health problem. Ninety-two percent (92.6%) reported sticking
      to one uninfected partner as a means of prevention and 88% reported use of condom
      as preventive measure. However, only 16.6% of the total respondents claimed to
      have used condom with their partners within the last 3 months. Although they are
      knowledgeable about HIV/AIDS, many do not practice what they know. University of
      Ibadan students are sexually active and their under-rating of heterosexual route
      as a major route of transmission suggests the urgent need for an organized
      educational programme of HIV/AIDS prevention for the University students.

PMID- 15971551
TI  - Prevalence of irritable bowel syndrome in a Nigerian student population.
AB  - Irritable bowel syndrome (IBS) is a widely recognized disorder accounting for up
      to 50% of referrals to gastroenterologists in the Western world. Existing
      literature had suggested that its prevalence is low among native Africans. The
      objective [corrected] is to document the prevalence of IBS in this environment. A
      cross-sectional study of clinical students at the Jos University Medical School
      and the School of Medical Laboratory Technology in Jos University were cohorted.
      Questionnaires based on the Rome II criteria were administered to 330 students
      (221 males and 109 females). Irritable bowel syndrome was present in 86 (26.1%)
      of the subjects, being present in 58 (26.4%) of the males and 28 (25.7%) of the
      females respectively (OR 0.97, 95% CI 0.57-1.63, p = 0.89). The mean age of
      subjects with IBS was 26.3 +/- 4.0 years and that of subjects without IBS was
      26.5 +/- 3.8 years, p = 0.6. The majority (54.8%) of the subjects did not
      consider their symptoms as illness and therefore did not seek any form of care.
      More males sought medical care compared to females (19.6% vs. 3.6% respectively,
      p = 0.02). Depressive symptoms were present in 21 (24.4%) of subjects with IBS
      compared to 36 (14.8%) of those without (p = 0.06). Irritable bowel syndrome is a
      common disorder in the student population of a medical school in Northern
      Nigeria.

PMID- 15971552
TI  - The effect of modulation of glutathione levels on markers for aflatoxin B1
      induced cell damage.
AB  - The modulatory effect of glutathione levels on markers for aflatoxin B1 (AFB1)
      induced cell damage has been investigated in the rat (susceptible specie) and the
      (mouse resistant specie). The concentration of GSH was depleted and increased by
      administering paracetamol (PAM) and cysteine respectively and activities
      ofglutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT)
      were determined. The effect ofAFB1 on hepatic lipid peroxidation in both species
      was also investigated. Treatment of rats with 2 mg/kg.bwt AFB1 intraperitoneally
      caused a depletion of GSH in the liver to a minimum at 6 h (80% of the control
      value) and the level returned to normal after 24 h. GST was similarly increased
      to a maximum at 6 h and the level also returned to normal after 24 h. GSH and GST
      activities were not significantly affected in AFB1-treated mice. Orally
      administered PAM (400 mg/kg.bwt) caused a depletion of GSH with a minimum at 6 h
      (59% and 36% of the control rats and mice respectively). Pretreatment of AFB1
      with PAM produced a serious depletion at 6 h (34% and 35% of the control rats and
      mice respectively). GST activities were also marginally increased in both
      animals. AFB1 pretreatment mediated (P < 0.001) hepatic lipid peroxidation in
      rats but not in mice as assessed by the formation of thiobarbituric acid reactive
      substances (TBARS). Treatment of rats and mice with oral cysteine (50 mg/kg bwt)
      elicited a significant elevation of GSH. Administration of cysteine with AFB to
      rats attenuated the toxic effects of AFB1 on GSH and inhibited the formation of
      TBARS. gamma-GT activity was significantly increased when AFB1 alone was
      administered to rats but was not increased (P > 0.05) when cysteine was
      pretreated alone with AFB1. Combined treatment of AFB, and PAM induced 177%
      increase in gamma-GT activity. Overall, our results suggest that the metabolism
      of aflatoxin B, by GSH does not lead to the formation of toxic products but
      rather GSH plays a protective role in AFB1-induced cell damage and GSH pathway is
      less utilised in mice.

PMID- 15971553
TI  - Normal values of echocardiographic parameters of apparently healthy adult
      Nigerians in Zaria.
AB  - The usefulness of echocardiography as a non invasive tool in the assessment of
      cardiac function is well established. Ninety two (54 males and 38 females)
      apparently healthy adult Nigerians were assessed echocardiographically to
      determine the normal values for the commonly measured parameters in our area of
      clinical practice. The mean age, body mass index (BMI), cardiothoracic ratio
      (CTR) and electrocardiographic left ventricular hypertrophy (ECG - LVH) were 51.4
      +/- 11.15 years, 23.85 +/- 4.91 kg/m2, 0.49 +/- 0.05, and 27.3 +/- 7.46 mm
      respectively. The mean systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and mean arterial pressure ('MAP) were 125.0 +/- 9.94, 79.7 +/- 6.23 and
      94.7 +/- 6.54, mmHg respectively. While the results of the echocardiographic
      measurements followed the same pattern as other published reports from outside
      Nigeria especially with relation to age, there were still some differences in
      terms of absolute values. This emphasizes the need to have our own normal
      reference values. A multicenter study across the country involving much larger
      number of subjects is required to establish normal reference values for Nigeria.

PMID- 15971554
TI  - Quality of life among primary liver cell carcinoma patients in Ibadan, Nigeria.
AB  - A descriptive prospective study was conducted to evaluate the quality of life of
      patients with primary liver cell carcinoma at the University College Hospital,
      Ibadan, Nigeria. Quality of life (QOL) was evaluated using a modified WHO QOL
      Field Trial version questionnaire of December 1996. The QOL parameters include
      body pains, energy and acceptability of bodily appearance among others. Thirty
      four patients aged between 23-74 years with a mean age of 49.6 +/- 13.4 were
      assessed. There were 28 (82.4%) males and 6 (17.6% females) (M/F = 4.6:1). Only
      about thirty percent of the patients rated their quality of life as being good or
      very good, with 70% rating their quality of life as very poor, poor or neither
      poor nor good. Eighty five percent of the patients were dissatisfied with their
      health, with 44.1% describing their health as very dissatisfying and only less
      than 10% enjoying satisfactory health. Eighty two percent of the patients
      responded that physical pain prevented them from doing what they want to do from
      moderate to extreme extent. All responders believed they require medical
      treatment to function in their lives with 22 (64%) requiring it very much.
      Seventeen (50%) of the patients had not enough energy at all for their daily
      activities, while 21 (61.7%) found their bodily appearance unacceptable to them.
      Fourteen (41.2%) did not receive adequate information they required about their
      day-to-day life. We conclude that our patients with PLCC have a low QOL rating
      and measures such as pain relief, reduction of bodily disfigurement and
      information to patients need to be put in place in order to improve their QOL.

PMID- 15971555
TI  - Knowledge and practices of traditional birth attendants in prenatal services in
      Lagos State, Nigeria.
AB  - A questionnaire-based study was conducted on 189 Traditional Birth Attendants
      (TBAs) on their knowledge and practices in prenatal services. Only 86 (45.5%) of
      them associated cessation of menstrual period with pregnancy while others use
      mystic power 46 (24.3%), early morning sickness, pallor of conjunctiva and
      reaction to herbs 56 (29.6%) to detect pregnancy. Fundal height n=76 (40.2%),
      palpation n=82 (43.4%), special soaps and soups n=52 (27.5%) and special devices
      n=8 (4.2%) are used to determine stages of pregnancy. Foetal health status is
      determined by regular foetal movements n=95 (50.3%), mystic power n=15 (8%), soap
      n=2 (1.1%), special concoction 9 (4.8%), health status of mother n=67 (35.4%) and
      foetal heart beat n=24 (12.7%). Ninety seven (51.3%) of them used herbal
      treatment, 77 (40.7%) used incantations, 189 (100%) used special soaps as their
      main methods of delivery, while only 18 (9.5%) of respondents refer difficult
      cases to hospitals. Instruments used for separating cord were blade 123 (65.1%)
      and scissors 40 (21.1%). Symptoms recognized by the TBAs as signs of
      complications in pregnancy were dizziness, swollen feet, pallor, tiredness,
      absent foetal movement, loss of appetite, heaviness, pain in back/stomach/side,
      weight loss, vomiting, bleeding, fever/malaria, head ache, bad dream, premature
      or delayed labour. Although some of them recognized some danger signs in
      pregnancy and labour, only very few would refer difficult cases for emergency
      obstetric interventions. Clear protocols for management and referral, which are
      necessary for improved maternal survival, should be provided through regular
      training of the TBAs.

PMID- 15971556
TI  - Gross morphological studies on the effect of cyanide on the developing cerebellum
      of wistar rat (rattus novegicus).
AB  - The teratogenic effect of maternal cyanide consumption on the gross morphology of
      the post-natal phase of the developing rat cerebellum was studied. Twenty
      pregnant female rats weighing between 170 g and 190 g were separated into control
      and experimental groups. The control animals were fed a standard diet of mice
      cubes, while the experimental animals were fed 500 ppm potassium cyanide, mixed
      with the standard diet. The diets were fed to the animals and their litters in
      separate cages and water provided ad libitum during gestation and to the
      offspring after birth. After birth, the offspring (five per group) of days 1, 9,
      14, 21, 28 and 50 were weighed, killed by cervical dislocation and the gross
      parameters studied. In the experimental animals, no significant differences were
      observed in the studied parameters between the control and experimental animals
      on day 1. A significant reduction in body weight was observed on day 14 (P <
      0.05). The brain weight was significantly reduced on day 9 (P < 0.05). Similarly,
      the cerebellar weight was significantly reduced on days 14,21 and 28 (P < 0.05).
      The maximum vermal length was significantly reduced on day 50 (P < 0.05), and the
      maximum side-to-side dimension of the cerebellum was also reduced on day 28 (P <
      0.05). There was no reduction in the thickness (anteroposterior dimension) of the
      cerebellum in the experimental group (P > 0.05). From the result, it is inferred
      that maternal consumption of 500 ppm cyanide causes reduction in the cerebellar
      weight, vermal length and side-to-side dimension of the developing cerebellum in
      postnatal life in rats.

PMID- 15971557
TI  - Pregnancy impairs resistance of C57BL/6 mice to Leishmania major infection.
AB  - To determine if gestational factors affect the severity of L. major infection,
      this study assessed the levels of IL-4 mRNA and IFN-gamma mRNA in popliteal lymph
      node cells of pregnant C57BL/6 mice mated at 5 hours, 16 hours and 15 days post
      L. major infection using PCR. Infected pregnant C57BL/6 mice developed larger
      cutaneous footpad lesions compared with non-pregnant infected C57BL/6 mice. The
      resolution of footpad lesions commenced after 8th week in C57BL/6 mice mated at
      16 hrs post L. major infection but 12 weeks in C57BL/6 mice mated at 5 hrs and 15
      days post L. major infection. C57BL/6 mice that were infected 20 days post partum
      resolved L. major infection effectively. But, the lesions in infected pregnant
      C57BL/6 mice and infected non-pregnant C57BL/6 mice were not as large as in
      susceptible BALB/c mice. The mean litter weights were similar in pregnant
      infected C57BL/6 mice mated at different stages of L. major infection but were
      slightly lower than weights of litters from pregnant uninfected C57BL/6 mice. In
      5 days infected pregnant C57BL/6 mice, the levels of IFN-gamma were raised
      compared with the levels of IL-4 but those mated at 15 days post L. major
      infection had highest level of IFN-gamma mRNA. In 10 days pregnant infected
      C57BL/6 mice, levels of IL-4 were raised compared with IFN-gamma but mice mated
      at 16 hrs post L. major infection had highest level of IL-4. In 15 days pregnant
      infected mice, the levels of IL-4 were higher than IFN-gamma irrespective of the
      stage of L. major infection when the mice were mated. Mice infected with L. major
      20 days post-partum produced more IFN-gamma than IL-4 from 16 hrs post L. major
      infection onwards. It may be concluded that increased IL-4 in pregnant infected
      C57BL/6 mice impairs the resistance of C57BL/6 mice to L. major infection
      especially in mice that were pregnant before effective immunity (5 hours post L.
      major infection) is mounted against L. major infection.

PMID- 15971558
TI  - The pattern of home treatment of malaria in under-fives in south eastern Nigeria.
AB  - Malaria remains a major public health problem in most countries of the tropics
      with high morbidity and mortality. The toll of the disease is highest on the
      under-fives. The actions mothers take in the management of children with malaria
      is important in the fight to check the malaria scourge. A cross sectional survey
      was carried out in two states in southeast Nigeria--Abia and Anambra states. A
      multi-stage sampling technique was used to select the subjects. One thousand two
      hundred and sixty mothers with children under five years of age were selected
      from 6 Local Government Areas in the two states. Trained interviewers were used
      to conduct the survey. The mean age of the mothers was 30.51 +/- 6.76. Over 95%
      (1016) of the respondents had at least a primary school education. The first line
      of actions mothers took when their under-five children had malaria showed that
      54.5% (687) of them either procured medicines from the patent medicine dealers or
      used medicines that were in the home. The two most commonly used drugs for
      malaria treatment for under-fives were chloroquine 65.4% (824) and
      pyrimethamine/sulfadoxine 12.3% (155). Between 11.5% and 46% of the mothers used
      correct doses of chloroquine syrup while 5.3% and 11.5% of them used correct
      doses of chloroquine tablets. The proportion of mothers that used correct doses
      of pyrimethamine/sulfadoxine tablets was comparatively higher (36.4% and 75%)
      than the others. Large proportion of mothers (61%) who manage malaria at home, do
      so inappropriately. Proper health education needs to be set up to enlighten the
      populace on mode of home treatment for malaria in order to reduce the disease
      burden on families.

PMID- 15971559
TI  - Thermal injuries in under-4-year-old children: the Lesotho experience.
AB  - The Queen Elizabeth II Hospital is the apex of the health care services in the
      Kingdom of Lesotho but has no designated burns unit. A review of patients managed
      during a 5-year period was done to document our experience so as to show what can
      be achieved even without a standard burns unit. We reviewed the clinical course
      of children who were admitted for care of acute thermal injuries during a 5-year
      period, May 1997 to April, 2002 inclusive. All were treated in the children
      surgical ward in accordance with a protocol of care emphasizing urgent care of
      shock, accurate fluid therapy, open wound care and early enteral feeding. Ninety
      eight children (51 males and 47 females) aged 4 months to 43 months (mean 21.66
      +/- 11.30 months) were admitted on account of acute thermal injuries during the
      study period. The injuries included scalding (46%) involving predominantly the
      upper part of the body and full thickness burns (87%). Skin grafting was needed
      in 82% of the patients. The common complications were infection, fluid imbalance,
      respiratory problems, and contracture deformities. The mean duration of hospital
      stay was 40 +/- 4.43 days and the case fatality rate was 9%. The case fatality
      rate in this series is considered high and could be improved if there were a well
      staffed specialized burns unit.

PMID- 15971560
TI  - Dysmenorrhoea and menstrual abnormalities among postmenarcheal secondary school
      girls in Maiduguri Nigeria.
AB  - Four Hundred and fifteen post menarcheal secondary school girls selected randomly
      from six secondary schools in Maiduguri metropolis were interviewed with the aid
      of questionnaires to find out their ages at menarche and associated menstrual
      problems, regularity of menstrual cycle, menorrhagia and dysmenorrhoea within the
      first two years following menarche. Their ages ranged between 12 and 21 years.
      Twenty six students were three months post menarche, 187 were 4-12 months post
      menarche.'The mean menarcheal age was 13.6 years. Menorrhagia was a very rare
      form of menstrual abnormality. Early menarche especially between the ages of 12
      to 14 years was found to be associated with higher frequency of irregular
      menstrual cycles while this improves with late onset menarche. About 45% had one
      form of menstrual abnormality, amenorrhoea (4.6%), oligomenorrhoea (18%) and
      polymenorrhoea (21%). These were almost uniformly associated with all groups.
      Over 80% had attained menarche by age of 14 years. Dysmenorrhoea was just
      slightly commoner by the ages of 15 and 16 years when it occurs more frequently.

PMID- 15971561
TI  - Ruptured uterus in a primigravida: a case report.
AB  - Maternal mortality and morbidity have remained very high in the developing
      countries and one of its commonest causes is ruptured uterus, which in a
      primigravida is rather unusual. The patient reported was a primigravida with no
      previous uterine scar who had prenatal care and delivery of a live male infant at
      a private clinic in Ibadan. The identifiable aetiological factors in this case
      are pitocin augmentation and manual removal of the placenta. Fortunately, a
      timely exploratory laparatomy averted another mortality. This is not usually the
      case in the majority of high-risk patients labouring outside a proper hospital
      setting consequent upon a declining economy and the rising influence of religion.
      Methods to reduce this obstetric catastrophy are discussed.

PMID- 15971562
TI  - Gall bladder perforation: report of 3 cases.
AB  - We report 3 cases of gall bladder perforation treated in this centre between
      January 1996 and June 2001. These were compared with Neimier's original
      classification of types of gall bladder perforation and areas of difficulty in
      management emphasised. The literature was also reviewed.

PMID- 15971563
TI  - Intra-oral squamous cell carcinoma in Nigerians under 40 years of age: a
      clinicopathological review of eight cases.
AB  - Intra-oral squamous cell carcinoma (SCC) is a disease commonly seen in patients
      aged 50 and above. A recent report on intra-oral SCC in the Nigerian population
      placed the mean age of occurrence for the disease at 50.7 years for male and 49.6
      years for females. Age is recognized to be an important factor in the onset and
      outcome of diseases like cancer. The focus of this study was to conduct a
      clinicopathological review on the incidence, pattern of presentation, management
      and outcome of the disease in patients aged 40 years and below seen at the
      University College Hospital Ibadan, between 1980-1995. During the period under
      review the total number of cases of SCC was 104, out of which 8 (7.7%) occurred
      in patients aged 40 years and below. The figure is higher than that of 1-3%
      obtained in Caucasian studies. The 5 year survival rate of our patients was nil.

PMID- 15971564
TI  - HIV/AIDS as an epidemic: ethical issues at the 20th anniversary.

PMID- 15971565
TI  - HIV/AIDS and bioethics: historical perspective, personal retrospective.
AB  - Problems posed by HIV/AIDS differ from those of past epidemics by virtue of
      unique properties of the causative agent, dramatic societal changes of the late
      20th century, and the transition of medical practice from a professional ethic to
      a technology-dependent business ethic. HIV/AIDS struck during the coming-of-age
      of molecular biology and also of bioethics, and the epidemic stimulated the
      growth of both disciplines. The number of articles published about AIDS and
      ethics (as identified by a MEDLINE search) peaked in 1990, just before the peak
      incidence of AIDS in the United States. The character of ethical dialogue has now
      shifted from familiar moral quandaries such as civil liberty versus public
      welfare to concerns about vaccine trials and public policy toward the developing
      world. Physicians and other health care workers who were involved from the onset
      endured something of an emotional roller coaster. Their compassion-based work
      ethic was to a large extent replaced by a competence-based work ethic after the
      introduction in 1996 of highly active antiretroviral therapy. The abundant recent
      literature on "professionalism" in medicine makes scant mention of AIDS/HIV. The
      disruptive effect of AIDS/HIV on society would have been substantially greater
      had relevant technology such as the ability to isolate retroviruses and potent
      therapy against tuberculosis not been in place. This sobering consideration,
      along with such recent events as the use of bioterrorism against civilian
      populations, suggests new relevance for Potter's definition of "bioethics" as a
      science of survival in which the biology of ecosystems must be taken into
      account.

PMID- 15971566
TI  - The limits of privacy: surveillance and the control of disease.
AB  - What justified the Center for Disease Control's 1999 determination to require HIV
      case reporting? Why were names necessary? Why did opponents view the reporting of
      names with such alarm? This paper retells the history of the encounters over HIV
      reporting that had occurred since the mid 1980s. In placing HIV reporting within
      a larger context, however, we understand the clash between privacy and public
      health necessity as a complex issue, both in historical and contemporary
      practice. By underscoring the similarities and differences with the histories of
      surveillance for other infectious diseases, vaccination, occupational diseases,
      cancer, and birth defects, and HIV reporting internationally, we can better
      understand the implications of the HIV debate for an ethics of surveillance more
      generally.

PMID- 15971567
TI  - What are the public obligations to AIDS patients?
AB  - The operating assumption in most discussions of health policy is that government
      has some responsibility for the health of its citizens and that it may
      legitimately tax, subsidize, and regulate its citizens in the exercise of that
      responsibility. On this assumption, public obligations to HIV/AIDS patients are a
      function of their needs in relationship to other health needs. This paper
      challenges the operating assumption by arguing that it cannot be grounded in the
      obligations that individuals have to each other. The paper rests on its own
      assumption: the moral theory of individualism. On this theory, individuals are
      ends in themselves who have the right to choose their own actions and uses of
      their resources; they do not have unchosen obligations to help others. In regard
      to HIV/AIDS patients, consequently, individuals have no duty to help, nor any
      other obligation beyond that of respecting their rights; and there is no valid
      basis for government regulations or subsidies on their behalf. The paper argues
      against the two approaches commonly used to defend a more expansive view of
      individual obligations and the role of government. The first is the assumption of
      welfare rights to goods and services; the second is the assumption that
      distributive justice requires some redistribution of health care resources.

PMID- 15971568
TI  - AIDS and sex: is warning a moral obligation?
AB  - Common-sense holds that morality requires people who know that they are infected
      with the Human Immunodeficiency Virus (HIV) to disclose this fact to their sexual
      partners. But many gay men who are HIV-positive do not disclose, and AIDS Service
      Organizations (ASOs) promote public-health policies based on safer sex by all,
      rather than disclosure by those who know that they are infected. The paper shows
      that the common-sense view follows from a minimal sexual morality based on
      consent. ASOs' seeming rejection of the view follows from their need to take
      seriously widespread weakness of will in the realm of sexuality. The author
      argues that gay men take themselves to follow the common sense view, but hold
      that the possibility of a partner's HIV infection is background information that
      need not be disclosed for sexual consent. This suggestion is criticized. The
      paper concludes with a consideration of HIV disclosure and sexual ethics outside
      of the gay community and of legal restrictions on the sexuality of the HIV
      positive.

PMID- 15971570
TI  - The West's moral obligation to assist developing nations in the fight against
      HIV/AIDS.
AB  - The HIV/AIDS epidemic is increasingly a disease of the disadvantaged, a destroyer
      of nations, and a threat to global security and well-being. But this need not be
      so: the world has the scientific knowledge, technological innovations, and
      financial resources to significantly reduce the spread and suffering caused by
      the disease. This paper argues that the wealthy nations of the world, led by the
      United States, have a moral obligation to offer much greater assistance to
      developing countries where the epidemic is most severe. Using Zimbabwe as a case
      study, this essay examines the immediate and underlying factors behind the
      epidemic in order to make realistic and affordable policy recommendations that
      include new investments in global health care, debt relief, and long-term
      economic development. By demonstrating our ability to dramatically affect the
      future course and consequences of this unprecedented epidemic, the paper
      concludes that greater action is not only in the interest of public health, but
      is also a moral imperative. By investing the necessary resources to improve
      public health and to reduce global poverty, we promote and extend the fundamental
      rights and values that we profess to hold dear.

PMID- 15971571
TI  - AIDS in the Third World: how, if at all, do we help?
AB  - The duty to help our fellows is not the same, and not stringent in the same way
      as the familiar duties to refrain from violence to others, and to be honest. In
      general, being helpful to others is commendable, and to be held up as a virtue.
      Only in cases where reciprocity is possible and likely may we speak of anything
      stronger along this line. Moreover, the case of AIDS in Africa is further
      complicated by the fact that it is easily preventable by readily understandable
      behavior alterations. However, there are certain possible spin-offs, especially
      from mutation, which can happen when, as with AIDS, there are millions of cases.
      So we in the west have some further, reason for concern and action than sheer
      good will. What can be done is especially difficult because of cultural factors
      of major order. Serious investigation of how, nevertheless, to get the message
      across is clearly in order. Otherwise, we cannot and, as a nation, should not,
      try to do much more.

PMID- 15971569
TI  - Rights and duties of HIV infected health care professionals.
AB  - In 1991, the CDC recommended that health care workers (HCWs) infected with HIV or
      HBV (HbeAg positive) should be reviewed by an expert panel and should inform
      patients of their serologic status before engaging in exposure-prone procedures.
      The CDC, in light of the existing scientific uncertainty about the risk of
      transmission, issued cautious recommendations. However, considerable evidence has
      emerged since 1991 suggesting that we should reform national policy. The data
      demonstrates that risks of transmission of infection in the health care setting
      are exceedingly low. Current policy, moreover, does not improve patient safety.
      At the same time, implementation of current national policy at the local level
      poses significant human rights burdens on HCWs. Consequently, national policy
      should be changed to ensure patient safety while protecting the human rights of
      HCWs. This article proposes a new national policy, including: (1) a program to
      prevent bloodborne pathogen transmission; (2) a responsibility placed on infected
      HCWs to promote their own health and well-being and to assure patient safety; (3)
      a discontinuation of expert review panels and special restrictions for exposure
      prone procedures; (4) a discontinuation of mandatory disclosure of a HCW's
      inflection status; and (5) the imposition of practice restrictions if a HCW is
      unable to practice safely because of a physical or mental impairment or failure
      to follow careful infection control techniques. A new national policy, focused on
      management of the workplace environment and injury prevention, would achieve high
      levels of patient safety without discrimination and invasion of privacy.

PMID- 15971572
TI  - [Prophylactic and therapeutic vaccines against Alzheimer's disease].
AB  - Beta-amyloid(Abeta) immunization as vaccines has now become a promising approach
      for the prevention and treatment of Alzheimer's disease (AD)after its debut in
      1999. Transgenic mouse models of AD that develop age-dependent Abeta deposition,
      damage to the neuropil, and behavioral deficits have enabled researchers to test
      if the approach can influence these AD-like pathologic changes in their brains.
      Active immunization with different forms of A beta and protocols have been shown
      to decrease brain Abeta deposition and improve cognitive performance in these
      mice models in the following studies. Although the phase II clinical trials of
      active immunization with Abeta(AN1792)were halted last year due to the occurrence
      of CNS inflammation in a small subset of patients, researchers found that strong
      humoral responses can be induced by the vaccination. Furthermore, the active
      immunization also brings an almost complete clearance of Abeta from much of the
      cerebral cortex. Abeta specific antibodies are believed to cross blood-brain
      barrier by minimal destroy of vascular wall where amyloid depositions exist.
      Three possible mechanisms on removal of Abeta deposition from brain have also
      been reviewed. Still some problems should be clarified before this strategy could
      be applied for clinical therapy. Whether vaccination will improve the cognitive
      decline in AD patients will depend upon clinical assessments, which was vital to
      destiny of the approach.

PMID- 15971573
TI  - [Advances in molecular regulation of artemisinin biosynthesis].
AB  - Artemisinin, a new and a very potent antimalarial drug, is produced by the
      Chinese medicinal herb Artemisia annua L. It is a sesquiterpene lactone with an
      endoperoxide bridge and is active against chloroquine resistant forms of
      Plasmodium falciparum. The relatively low yield (0.01% - 0.6%) of artemisinin in
      A. annua is a serious limitation to the commercialization of the drug. Therefore,
      a through understanding of the biosynthetic pathway and the characterization of
      the involved enzymes are important for the biology production of artemisinin.
      This review is focused on the recent progress in the molecular regulation of
      artemisinin biosynthesis from the following aspects: the biosynthetic pathway of
      artemisinin, the key enzymes involved in artemisinin biosynthesis, and the
      molecular regulation of artemisinin biosynthesis. The biosynthetic pathway of
      artemisinin belongs to the isoprenoid metabolite pathway, the key enzymes
      involved in the biosynthesis of artemisinin include: 3-hydroxy-3-methylglutaryl
      CoA reductase (HMGR), farnesyl diphosphate synthase (FDPS), and amorpha-4, 11
      diene synthase, of which amorpha-4, 11-diene synthase catalyzes the cyclisation
      of the ubiquitous precursor farnesyl diphosphate to the highly specific olefinic
      sesquiter-pene skeletons and has been postulated as the regulatory step in the
      biosynthesis of artemisinin. Recently the gene encoding of the amorpha-4, 11
      diene synthase has been cloned and the functional expressions have been studied
      by several research teams, therefore, the breakthroughs in production of
      artemisinin could hopefully be achieved by metabolic engineering of the plant, in
      particular, by over-expressing enzyme(s) catalyzing the rate limiting step(s) of
      artemisinin biosynthesis or by inhibiting the enzyme(s) of other pathway
      competing for its precursors. Besides, the effects of the heterogenesis
      isoprenoid pathway related genes on artemisinin biosynthesis of the transformed
      plants were also discussed.

PMID- 15971574
TI  - [Virulence genes of Agrobacterium tumefaciens and analysis function of its
      biology].
AB  - Chromosomal virulence genes acvB, abvA, chvA of Agrobacterium tumefaciens were
      cloned with the technique of transposon 5 insertion. The chromosome genes are
      necessary for Agrobacterium tumfaciens absorbing to cell ular surface of plant,
      the adherence reaction can't be executed and result in losing the toxicity if
      mutations are occurred in some chromosome genes. The chromosome toxicity gene is
      inactivated due to transposon Tn5 be inserted and the accept ant cell infected
      with Agrobacterium tumefaciens can't cause tumor ultimately. This article briefly
      introduces the research way of thinking and strategy of this technique and the
      important roles of every gene, which are taken of in the process of T-DNA's form,
      transfer, integration, and expression etc. This article also gives a presumption
      to T-DNA's transport: The plant cell wall's porin may be T-DNA's natural channel.

PMID- 15971575
TI  - [The OPG/RANKL/RANK system and bone resorptive disease].
AB  - The OPG/RANKL/RANK system plays an important role in osteoclastogenesis and
      represents a great progress in bone biology. RANKL, which expresses on the
      surface of osteoblast/stromal cells and activated T cells, binds to RANK on the
      osteoclastic precursors or mature osteoclasts, and promotes osteoclastogenesis
      and bone resorption. While osteoprotegerin (OPG), which is expressed by
      osteoblasts/stromal cells, strongly inhibits bone resorption by binding to its
      ligand RANKL and thereby blocks the interaction between BANKL and RANK. A number
      of cytokines and hormones exert their effects on bone metabolism by regulating
      the OPG/RANKL ratio in the bone marrow microenvironment. RANK is also expressed
      on mammary epithelial cells and RANKL expression in these cells is induced by
      pregnancy hormones, RANKL and RANK are essential for the formation of the
      lactating mammary gland and the transmission of maternal calcium to neonates in
      mammalian species. Modulation of these systems provides a unique opportunity to
      develop novel therapeutics to inhibit bone loss in osteoporosis, rheumatoid
      arthritis, and bone metastasis of cancer. Further research should be focused on
      the cooperation of OPG/RANKL/RANK system with other signal pathways and the
      interactions among bone remodeling, immune system and endocrinology system.
      Currently, the development of OPG analogues or compounds which may stimulate OPG
      expression is becoming an attractive industry which may be profitable to both
      patients and manufacturers.

PMID- 15971576
TI  - [Identification and cloning of a novel gene involved in EPS biosynthesis of
      Xanthomonas campestris pv. campestris].
AB  - Xanthomonas campestris pv. campestris ( Xcc), causative agent of the black rot
      disease of cruciferous crops worldwide, produces large amount of extracellular
      polysaccharide( EPS), which has found wide applications in industry. In order to
      clone genes involved in EPS biosynthesis, Xcc wild-type strain 8004 was
      mutagenized with transposon Tn5gus A5, and a number of EPS-defective mutants were
      isolated. The Tn5gusA5 insertion sites in the mutants were analyzed by using
      thermal asymmetric interlaced PCR(TAIL-PCR), and the corresponding genes were
      identified by homology blast to the completely sequenced genome of Xcc 8004
      strain. A novel gene, waxE, identified from the EPS-defective mutant 151D09, was
      found to be disrupted by the insertion of Tn5gusA5 in the open reading frame(ORF)
      with genome coordinates 4478998bp to 4479819bp.This gene showed 52% similarity to
      the kdtX gene of Serratia marcescens and 50% to the waaE of Klebsiella pneumoniae
      at amino acid level, with characteristics of glycostransferase 2 family domain.
      In order to identify the function of waxE gene, waxE gene deletion mutant of Xcc
      8004 was constructed by gene replacement strategy in which waxE gene of genome
      was replaced by kanamycin resistant gene kan. The waxE gene deletion mutant
      strain, named Xcc 8570, was confirmed by both PCR and southern analysis. The
      growth rate of the deletion mutant 8570 in rich medium was not affected, but the
      EPS yield reduced by 35% as compared with the wildtype strain 8004. The deletion
      mutant could be completmented in trans with plasmid pLATC8976 harboring an intact
      waxE gene, and the EPS yield of the mutant was restored. The combined data showed
      that waxE gene involved in EPS biosynthesis in Xcc.

PMID- 15971577
TI  - [Application of Ac/Ds transposon system to genetate marker gene free transgenic
      plants in rice].
AB  - It is critical to generate marker gene free transgenic plants for
      retransformating or eliminating the potential harmfulness of marker gene and its
      product. In this study, Ac/Ds transposon system was developed for removal of hpt
      selection marker gene to obtain marker-free transgenic plants in rice ( Oryza
      sativa L.). Ds element containing the interesting gene bar was constructed next
      to the selection marker gene hpt to get Ds-T-DNA. Rice plants were transformed by
      Agrobacterium tumefaciens EHA105 containing Ac-T-DNA and Ds-T-DNA respectively.
      Rice plant containing single copy Ac-T-DNA was crossed with plant containing
      single copy Ds-T-DNA to obtain the F1 plant containing both Ac and Ds elements.
      F1 plant was self-crossed to produce F2 progeny in which T-DNA insert and
      transposed Ds element segregated independently. Two plants contained Ds element
      but no hpt marker gene in total 100 F2 plants. The result indicated that Ac/Ds
      transposon system could be used as a vector system for generating marker gene
      free transgenic plants in rice.

PMID- 15971578
TI  - [Expression, purification and serological reactivity of a chimeric antigen of
      GRA6 with P30 from Toxoplasma gondii].
AB  - Major surface protein (p30) and Dense Granule Antigen GRA6 of Toxoplasma gondii
      have good antigenicity, and could be used for detection of IgM against Toxoplasma
      gondii. GRA6 may complement P30 to reach more high sensitivity for detection of
      antibodies to Toxoplasma gondii, so, we try to express the chimeric protein of
      GRA6 and P30 by genetic engineering, identify its antignenicity and use for
      developing diagnosis reagent. Antigenic domains of p30 and GRA6 of Toxoplasma
      gondii were screened by analyzing their sequences using the software ANTHEWIN.
      Two DNA fragments encoding respectively antigenic domains of p30 and GRA6 were
      cloned, they were inserted into the same expression vector pET28a( + ) and
      expressed as a chimeric protein in Escherichia coli. BL21(DE3), the expressed
      chimeric protein of p30 with GRA6 in a form of inclusion body was about 25% of
      total proteins of E. coli. BL21(DE3). The inclusion body was washed once with
      0.5% Triton X-100 and dissolved with 0.5% SKL, after renaturation by gradient
      dialysis, the recombinant protein was purified by DEAE-Sepharose FF cation column
      and then detected with 12% SDS-PAGE, it exists mainly in the eluted peak with 300
      mmol/L NaCl and has high purity. By using enzyme-linked immunosorbent assay
      (ELISA), the recombinant protein was examined for reactivity with immunoglobulin
      M (IgM) antibodies in 6 sera from patients infected with Toxoplasma gondii ., it
      was reactive with all the 6 sera but not with sera from normal people, these
      results showed that the recombinant chimeric antigen has good antigenicity and
      specificity and could be used for detection of IgM against Toxoplasma gondii. The
      expressed chimeric protein could be used for epidemic investigation of Toxoplasma
      gondii, blood donor screening, especially for detection of pregnant women, and is
      of great significance in prevention of Toxoplasma gondii infection.

PMID- 15971579
TI  - [Selection of a peptide mimic the neutralization epitope of hepatitis E virus
      with phage peptide display technology].
AB  - Hepatitis E is an acute hepatitis casused by hepatitis E virus (HEV) in
      developing countries, where it occurs as cases sporadic and in epidemics form.
      The causative agent, hepatitis E virus, is transmitted primarily by the fecal
      oral route. HEV is icosahedron non-enveloped virus, and its genome is a single
      stranded, positive-sense, 3'-polyadenylated RNA about 7.5 kb in length. It
      contains three open reading frames (ORFs). Of which ORF1 codes for a polyprotein
      of 1693 amino acids and contain domains homologous to a viral methyltransferase,
      a papainlike cysteine protease, an RNA helicasre, and an RNA-dependent RNA
      polymerase, besides the most hypervariable region of the HEV genome. And ORF3
      codes for a 123-amino-acide-long polypeptide with unknown function. While the
      major viral capsid protein (pORF2, ORF2 codes) of 660 amino acid was showed to
      contain the protective epitope. The bacterially expressed polypeptide disignated
      as NE2 has been proved to be a protective antige. And the anti-NE2 monoclonal
      antibodies (mAb) was screend, two of these mAbs 8C11 and 8H3 were showed to be
      against separate conformational neutralization epitope of hepatitis E virus
      (HEV). And these two mAb were used to screen for binding peptides from a 7
      peptides phage display library. After four rounds of panning, tweenty-one
      positive monoclonal phages (11 for 8C11, and 10 for 8H3) were selected and the
      inserted fragments were sequenced. The DNA sequence coding for the obtained
      dominant peptide 8C11 (N'-His-Pro-Thr-Leu-Leu-Arg-Ile-C', named 8C11A) and 8H3
      (N'-Ser-Ile-Leu-Pro-Tyr-Pro-Tyr-C', named 8H3A) were then synthesized and cloned
      to insert between amino acid 78 to 83 of hepatitis B core antigen (HBcAg), then
      expressed in E. coli. The recombinant proteins aggregate into homodimer or
      polymer on SDS-PAGE, and could bind with mAb 8C11 and 8H3 in Western blotting.
      Respectively, the recombinant protein C8C11A showed to be dimer mainly, which can
      bind with mAb 8C11. The monomer and dimer of C8H3A are in the same amount on SDS
      PAGE, but only the dimer could bind with mAb 8H3 on Western blotting. The
      renatured recombinant proteins were all showed to aggregate into virus like
      particles which were similar as HBcAg on transmission electron micrograph. The
      dominant peptide 8H3A (N'-Ser-Ile-Leu-Pro-Tyr-ProTyr-C') that selected out by mAb
      8H3 was further chemo-synthesized, and its binding activity was confirmed by
      BIAcore biosensor. The result showed that this 7-peptide can bind with mAb 8H3 in
      a big Ka and Kd form, which means the binding is not stable. These results
      implicated that conformational dependent neutralization epitope could be
      partially modeled by short peptide, which provided a feasible route for subunit
      vaccine development.

PMID- 15971580
TI  - [Influence of the reductase deficient Escherichia coli on the solubility of
      recombinant proteins produced in it].
AB  - The cytoplasm of E. coli is a reducing environment where cysteines do not engage
      in disulfide bonds. Any disulfide bonds that do appear are rapidly reduced
      through the action of disulfide reducing enzymes such as thioredoxin and
      glutaredoxin. To study the influence of E. coli cytoplasm on the solubility of
      recombinant proteins produced in it, bovine fibroblast growth factor (BbFGF),
      with single disulfide bond, and anti-HBsAg single-chain Fv (HBscFv), with two
      disulfide bonds, were selected as the pattern molecules of simple protein and
      complex protein, respectively. pJN98-BbFGF, a BbFGF expressing plasmid based on
      the vector pET3c, was constructed and transformed into normal host BL21(DE3) and
      a reductase deficient strain, E. coli Origami(DE3). At the same time, pQE-HBscFv,
      a HBscFv expressing plasmid was constructed and transformed into M15 [pREP4] and
      Origami(DE3). The recombinant BbFGF and HBscFv were produced in 2 types of
      bacteria and their solubilities and bioactivities were determined, respectively.
      It was found that the majority of BbFGF had formed inclusion body in the
      cytoplasm of BL21 (DE3) and all of them turned into soluble protein in
      Origami(DE3). It was also found the productivity of BbFGF in Origami (DE3) was 5%
      - 10% of the total protein and the value was 15% - 23% in BL21(DE3). BbFGFs
      produced in 2 recombinant bacteria were purified by cation exchange and heparin
      affinity chromatography. MTT assay revealed that the bioactivity of BbFGF
      purified from Origami(DE3) was higher than its counterpart from BL21(DE3). The
      ED50 of BbFGFs from different bacteria was 1.6ng/mL and 2.2ng/mL, respectively.
      As far as HBscFvs, both of them formed inclusion body in the cytoplasm of M15
      [pQE-HBscFv] and Origami [pQE-HBscFv]. The inclusion body was solubilized in
      6mol/L GuHCl, purified with a His-Trap column and then refolded by dialysis step
      by-step against buffers containing downtrend concentration of GuHCl. Indirect
      ELISA was applied to determine the HBsAg binding activity of HBscFvs. It was
      found there was no obvious difference between the bioactivity of refolded HBscFvs
      produced from 2 recombinant bacteria. On the other hand, the supernatant of
      Origami [pQE-HBscFv] lysate displayed weak bioactivity and its counterpart from
      M15 [pQE-HBscFv] displayed without any bioactivity. The soluble HBsFv in the
      cytoplasm of Origami [pQE-HBscFv] was purified by cation exchange and immobilized
      metal affinity chromatography (IMAC) and the yield was 1 - 2mg/L. Those results
      suggested that modification of the redox environment of E. coli cytoplasm greatly
      improved the solubility of recombinant disulfide-bonded proteins produced in it.
      In the next step, we had like to co-express of molecular chaperones or refoldase
      to raise the yield of soluble recombinant proteins, as well as optimizing the
      culture condition of the "oxidizing" E. coli.

PMID- 15971581
TI  - [Expression of human apolipoprotein A- I in baculovirus-insect cell system].
AB  - Apolipoprotein A- I is the major apolipoprotein in high-density lipoprotein known
      to have a wide range of physiological functions, the best-studied one of which is
      in regulating cholesterol metabolism and preventing arteriosclerosis. Human blood
      has been the only source of this protein. To facilitate further research and
      application, it is essential to produce it through genetic engineering. In the
      current research, the baculovirus-insect cell system was used to overexpress
      human apolipoprotein A- I . Two recombinant baculoviruses were constructed. The
      first one expressed a pro form of apoA- I lacking native signal peptide. The
      recombinant protein was found to remain mainly inside cells in the early phase of
      infection, while being largely excreted to the medium late in infection. The
      second one used a heterologous signal peptide, snake phospholipase A2 inhibitor
      alpha subunit signal peptide, to lead the secretion of mature apoA- I. In
      contrast to the first virus, recombinant apoA- I was found in the culture medium
      at the early phase of virus infection. The mature apoA- I was purified from
      culture medium using Phenyl Sepharose hydrophobic interaction chromatography
      (HIC) and eluted with water and Propylene. This work shows that snake
      phospholipase A2 inhibitor a subunit signal peptide can be used to secret human
      apoA- I in insect cells, but the efficiency of its secretion is limited when the
      expression level is high.

PMID- 15971582
TI  - [Study of recombinant stem cell factor].
AB  - Stem cell factor is an important hematopoietic growth factor. In this study, the
      human stem cell factor was produced by recombinant E. coli, and the structure and
      biological activity of the recombinant stem cell factor(rhSCF) was studied. It
      was indicated that the rhSCF was a uncovalent dimer in phosphate buffer,and had
      the correct mass spectra, mass peptides spectra, composition of amino acid, N
      terminal sequernce, C-terminal sequence and intrachain disulfide linkages, rhSCF
      alone or synergy with rhG-CSF could mobilze hematopoietic progenitors to blood in
      monkey.

PMID- 15971583
TI  - [Modification of the antiapoptotic ability of H18 hybridoma cells].
AB  - To construct eukaryotic expression vector containing murine bcl-XL and stably
      express it in H18 hybridoma cells in order to enhance hybridoma cells
      antiapoptotic ability. PCR was used to obtain 710bp murine bcl-XL cDNA from pGEM
      T-bcl-XL. Then the recombinant expression vector pEF-bcl-XL was constructed by
      cloning bcl-XL cDNA into eukaryotic expression vector pEF by Pst I and Xho I
      double digestion. After transfection into H18 hybridoma cells through
      lipofectamine 2000, the stable expression cell line was screened by 800mg/L G418.
      The expression of bcl-XL gene was detected by Western blotting. Flow cytometer
      was used to test the modified hybridoma cells ability to resist apoptosis induced
      by 0.4mmol/L Sodium Butyrate. The eukaryotic expression vector pEF-bcl-XL was
      successfully constructed and stably expressed in H18 hybridoma cells. Our data
      showed that stably transfected H18 cells expressed high levels of Bcl-XL. Under
      the condition of 0.4mmol/L NaBu, the production of antibody was to be
      significantly increased by more than 3-fold in stably transfected H18, which
      resulted from suppressing the NaBu-induced apoptosis and allowing stably
      transfected H18 cells to grow at higher viability and extend culture longevity by
      > 3 days. The increased culture longevity by inhibition of NaBu-induced apoptosis
      by inducible expression of Bcl-XL combined with the enhanced secretion of
      antibody by NaBu contributed to the enhancement of final antibody concentration
      in the stably transfected H18 cells culture. The final antibody concentration of
      stably transfected H18 cells in the presence of NaBu was three-fold higher than
      that of H18 cells culture in the absence of NaBu. Together, our results showed
      that butyrate is of practical interest for production of antibody. NaBu-induced
      apoptosis of hybridoma cells could be inhibited by inducible expression of Bcl
      XL. The expression of murine bcl-XL gene in hyridoma cells and the increasing
      antiapoptosis ability of hybridoma cells are of significance in further use of
      hybridoma cells in high density large scale cell culture.

PMID- 15971584
TI  - [Fermentative production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
      (PHBHHx) by recombinant Aeromonas hydrophila 4AK4 (pTG01)].
AB  - Copolyesters consisting of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx)
      (PHBHHx), a new type of biodegradable material, are receiving considerable
      attentions recently. The material properties are strongly related to the 3HHx
      fraction of PHBHHx. As the 3HHx fraction increase, crystallinity and melting
      point of PHBHHx decrease, flexibility and tractility increase. PHBHHx of
      different 3HHx fraction can meet different demands of commercial application and
      research. Aeromonas are the best studied PHBHHx-producing strains. Recent studies
      have been focused on optimizations of fermentative culture media and culture
      conditions for low-cost and efficient fermentative production. Aliphatic
      substrates such as long-chain fatty acid and soybean oil were used in the PHBHHx
      fermentation as the sole carbon source and energy source. Two-stage fermentation
      method was also developed for more efficient PHBHHx production. While studies on
      Aeromonas hydrophila revealed that the monomer composition of PHBHHx could not
      easily be regulated by fermentative process engineering methods such as changing
      substrates and fermentative conditions because precursors involved in the PHBHHx
      synthesis were all from the beta-oxidation pathway. In this study, phbA gene
      encoding beta-ketothiolase and phbB gene encoding acetoacetyl-CoA reductase were
      introduced into a PHBHHx-producing strain Aeromonas hydrophila 4AK4 so as to
      provide a new 3HB precursors synthesis way. phbA gene encodes beta-ketothiolase
      which can catalyze two acetyl-CoA to form acetoacetyl-CoA; phbB gene encodes
      acetoacetyl-CoA reductase catalyzing acetoacetly-CoA into 3HB-CoA which is the
      precursor of 3HB. The introduced novel 3-hydroxybutyrate precursor synthesis
      pathway allowed the recombinant strain to use unrelated carbon source such as
      gluconate to provide 3HB precursors for PHBHHx synthesis. Shake-flask experiments
      were carried out to produce PHBHHx of controllable monomer composition and
      fermentations in 5 L fermentor were also proceeded for confirmation of these
      result in large-scale culture. In flask culture, it was possible to reduce the
      3HHx mol fraction in PHBHHx from 15 % in the wild type to 3% - 12% in the
      recombinant by simply changing the ratio of gluconate to lauric acid in the
      culture media. When lauric acid was used as the sole carbon source, 51.5 g/L Cell
      Dry Weight (CDW) containing 62 % PHBHHx with 9.7 % 3HHx mol fraction was obtained
      in 56 hours of fermentation in a 5 liter fermentor. When co-substrates of sodium
      gluconate and lauric acid (1:1) were used as carbon sources, 32.8 g/L CDW
      containing 52 % PHBHHx with 6.7% 3HHx mol fraction was obtained in 48 hours of
      fermentation. These results showed the possibility for fermentative production of
      PHBHHx with controllable monomer composition.

PMID- 15971585
TI  - Enhancements in ethanol tolerance of a self-flocculating yeast by calcium ion
      through decrease in plasmalemma permeability.
AB  - Ca2+ at 1.64 mmol/L markedly increased ethanol tolerance of a self-flocculating
      fusant of Schizosaccharomyces pombe and Saccharomyces cerevisiae. After 9 h of
      exposure to 20% (V/V) ethanol at 30 degrees C , no viability remained for the
      control whereas 50.0% remained for the cells both grown and incubated with
      ethanol in Ca2+ -added medium. Furthermore, when subjected to 15% (V/V) ethanol
      at 30 degrees C, the equilibrium nucleotide concentration and plasma membrane
      permeability coefficient (P' ) of the cells both grown and incubated with ethanol
      in Ca2+ -added medium accounted for only 50.0% and 29.3% those of the control
      respectively, indicating that adding Ca2+ can markedly reduce plasma membrane
      permeability of yeast cells under ethanol stress as compared with the control.
      Meanwhile, high viability levels acquired by the addition of Ca2+ exactly
      corresponded to the striking decreases in extracellular nucleotide concentration
      and P' achieved with identical approach. Therefore, the enhancing effect of Ca2+
      on ethanol tolerance of this strain is closely related to its ability to decrease
      plasma membrane permeability of yeast cells subjected to ethanol stress.

PMID- 15971586
TI  - [The breeding and culture condition optimization of a high-biomass, selenium
      enriched yeast strain].
AB  - The yeast fusant ZFF-28, which is high in biomass production and rich in
      selenium, was constructed after mutagenesis and protoplasts fusion between yeast
      strains. The total selenium content of ZFF-28 is 1.8 and 1.0 times higher than
      that of the parental strains Saccharomyces cerevisiae ZY-67 and Saccharomyces
      kluyveri SZY-198 respectively. Using single factor tests and a L16(4(3) x 2(1))
      orthogonal design, the cultivation conditions was optimized as: 50mL culture in
      250mL shake flasks in molasses containing 6% sugar and 60microg/mL Se at 28
      degree C for 25h at 220 r/min, with the initial pH adjusted to 6.0 - 6.5. Under
      the optimized conditions, the biomass (dry weight) reached 8.2g/L and the Se
      content of the cells reached 2050microg/g, with organic and inorganic Se contents
      being 91% and 9% respectively.

PMID- 15971587
TI  - [Purification and characterization of glutamate dehydrogenase. from
      Corynebacterium glutamicum S9114].
AB  - Glutamate dehydrogenase (GDH) is a key enzyme in the biosynthesis of glutamate.
      The GDHs from Corynebacterium glutamicum S9114 the most commonly used strain in
      glutamate fermentation, were purified and their molecular structures and
      properties characterized. The coenzymes were also studied in the hope to increase
      glutamate production. Cells were harvested at mid-exponential phase by
      centrifugation and washed with Tris-HCl buffer containing DTT and EDTA (pH 7.5).
      The cells were then disrupted using a French pressure cell press and the
      supernatant was collected by centrifugation. The extract was concentrated by 70
      fold using the AKTA-100 FPLC system employing a DEAE-cellulose ion exchange
      column, a hydrophobic interaction chromatography (HIC) and Sephadex G-200 gel
      filtration. The purified extracts contained NADPH-dependent GDH and NADH
      dependent GDH. Both of the enzymes were highly specific for the coenzymes. The
      molecular masses of the NADPH-dependent GDH and its subunit were 188kD and 32kD
      respectively, suggesting the enzyme is a homo-hexamer. Our data reported for the
      first time the presence of NADH- dependent GDH in Corynebacterium glutamicum
      S9114, similar to other microorganisms containing both GDHs. The NADPH-dependent
      and NADH-dependent GDH in Corynebacterium glutamicum S9114 may participate in the
      assimilation and dissimilation of ammonia respectively. The absorptions of NADPH
      dependent GDH was very weak at 280nm but very high at 215nm, suggesting a low
      phenylalanine and tyrosine content in the enzyme.

PMID- 15971588
TI  - [Screening and characterization of DNA aptamers with hTNF-alpha binding and
      neutralizing activity].
AB  - Human tumor necrosis factor alpha (hTNF-alpha) is one of the most important
      inflammatory cytokines that acts as a mediator in inflammatory and immune
      response and plays a key role in host defense against infection. The over
      expression of hTNF-alpha is associated with serious consequences, such as shock,
      hypotension, thrombus, septicemia and even death. It has been implicated in many
      autoimmune and inflammatory diseases, such as rheumatoid arthritis, Crohn's
      disease, chronic heart failure and septic shock. Inhibiting the bio-activity of
      hTNF-alpha is one of the strategy for the treatment of these diseases. Compared
      with traditional recombinant protein drugs, small molecule drugs have many
      advantages, such as high affinity, low immunogenecity and low cost. Systematic
      evolution of ligands by exponential enrichment (SELEX) is a powerful method for
      the selection of oligonucleotides that bind with high affinity and specificity to
      target proteins. Such oligonucleotides are called aptamers, and are potential
      therapeutics for blocking the activity of pathologically relevant proteins. To
      obtain oligonucleotide aptamers specifically binding to TNF, a 40nt random DNA
      combinatorial library flanked by 31nt fixed sequences was chemically synthesized.
      The random library was amplified with PCR and subjected to selection by SELEX
      protocol against hTNFalpha. After incubation of the library with hTNFalpha, the
      mixture was blotted onto Immobilon-NC transfer membrane. The no-specific binding
      was washed away and the hTNFa binding aptamers were eluted and detached from the
      target protein. The eluted oligo nucleotides were amplified with PCR and served
      as the DNA library for the next round selection. After 12 rounds of such
      selection, the selected aptamers were cloned to pGEM-T vector. Positive clones
      were identified by restriction enzyme digestion and DNA sequencing. Oligo DNA
      were synthesized according to the sequence data and tested for their activities.
      Binding activity of the aptamers to hTNFalpha were detected by ELISA and dot blot
      with biotin-streptavidin-horseradish peroxidase system. Mouse L929 cells were
      used to test the anti-hTNFa activity of the DNA aptamers. The aptamers were
      incubated with hTNFalpha and added to the L929 cells. The results were read under
      microscope and with MTT staining. It was shown that these DNA aptamers bound to
      hTNFalpha with high affinity, and can inhibit the cytotoxicity of hTNFalpha on
      cell culture. The affinity of these aptamers are different and may related to
      their structure. These ssDNA aptamers are potential for the treatment and
      diagnosis of hTNFalpha related diseases.

PMID- 15971589
TI  - [Effects of dissolved oxygen and pH on Candida utilis batch fermentation of
      glutathione].
AB  - The effects of dissolved oxygen (DO) and pH on glutathione batch fermentation by
      Candida utilis WSH-02-08 in a 7 liters stirred fermentor were investigated. It
      was shown that DO concentration is an important factor in glutathione production.
      With the initial glucose concentration of 30 g/L and a 5 L/min air flow rate, and
      the agitation rate less than 250 r/min, the DO concentration was not sufficient
      to satisfy the oxygen requirement during the fermentation. With an agitation rate
      of more than 300 r/min, the cell growth and glutathione production were enhanced
      significantly, with the dry cell mass and glutathione production were 20% and 25%
      higher than that at 200 r/min. When C. utilis WSH 02-08 was cultivated in a batch
      process without pH control, cell growth and glutathione production were
      inhibited, likely due to a dramatic decrease in the pH. Intracellular glutathione
      leakages were observed when the pH was 1.5 or less. To assess the effect of pH on
      glutathione production, six batch processes controlled at pH 4.0, 4.5, 5.0, 5.5,
      6.0 and 6.5 were conducted. The yield was highest at pH 5.5, when the dry cell
      mass and yield were 27% and 95% respectively higher than fermentation without pH
      control. The maximal intracellular glutathione content (2.15 %) was also achieved
      at the pH. To improve our understandings on the effect of pH on the batch
      glutathione production, a modified Logistic equation and Luedeking-Piret equation
      were used to simulate cell growth and glutathione production, respectively, under
      different pH. Based on the parameters obtained by the nonlinear estimation,
      kinetic analysis was performed to elucidate the effect of pH on the batch
      glutathione production. The process controlled at pH 5.5 was proven to be the
      best due to the higher value of K(I) (substrate inhibitory constant in the
      Logistic equation), lower value of a and higher value of beta (slope and
      intercept in the Luedeking-Piret equation, respectively).

PMID- 15971590
TI  - [Purification and fingerprinting development of Salvia miltiorrhiza Bunge by high
      speed counter-current chromatography].
AB  - In an attempt to apply high-speed counter-current chromatography HSCCC for TCM
      fingerprints, the separation and purification of the Chinese medicinal plant
      Salvia miltiorrhiza Bunge of different localities was realized using the
      technique. The equipments used include a HSCCC (TBE-300) of Shenzhen Tauto
      Biotech containing three connected preparative coils (diameter of tube = 2.6mm,
      total volume = 300mL) and a 20mL sample loop and a HPLC from Shimadzu of Japan
      with a Ultrasphere C18 column (150 x 4.6mm ID, 5microm) and a 20microL sample
      loop. Salvia miltiorrhiza Bunge samples from 3 locations were separated by HSCCC
      in a Step-wise elution program with solvent systems A (hexane:ethanol: water =
      10:5.5:4.5) and B (hexane:ethanol: water = 10:7:3) at a speed of 900 r/min and a
      flow-rate of 2mL/min. All the 12 peak fractions were eluted within 13 hours. The
      contents of each component varied greatly in different samples, which confirmed
      previous observation that the locations and climates have a great impact on the
      TCM quality and also indicated a quality control system is necessary to safeguard
      the quality of the herb. The retention times of the 12 peak fractions from crude
      extracts of the samples were collected by HPLC and the absorption spectrums of
      the corresponding peaks were identified. The 12 components of the three crude
      samples were readily distinguishable and can be used as fingerprints of S.
      miltiorrhiza Bunge. The relative standard deviation of the HSCCC retention times
      was less than 3%, which satisfies the requirement of the national standard
      reference index. The components 7, 8 and 11 from the standards were identified to
      be crypototanshinone, tanshinone I and tanshinone II A respectively. This study
      demonstrates that if it is possible to apply HSCCC for TCM fingerprinting,
      especially with samples of high viscosity and highly absorptive components. The
      precision and the run time of fingerprinting can be further improved if larger
      volume and a temperature control system is used. With these and other
      improvements, HSCCC is expected to play an important role in TCM development.

PMID- 15971591
TI  - [CaCO3 stimulates alpha-ketoglutarate accumulation during pyruvate fermentation
      by Torulopsis glabrata].
AB  - A large amount of alpha-ketoglutarate (alpha-KG) (6.8 g/L) was accumulated in
      flask culture when CaCO3 was used as a buffering agent in the production of
      pyruvate by multi-vitamin auxotrophic yeast Torulopsis glabrata CCTCC M202019. In
      a 5 L jar-fermentor, less alpha-KG (1.3 g/L) was produced when NaOH was used to
      adjust the pH, while more alpha-KG (11.5 g/L) detected when CaCO3 was used as the
      buffer. In the latter case, the molar carbon ratio of pyruvate to alpha-KG
      (C(PYR)/ CalphaKG) was similar to that obtained in flask culture, suggesting the
      accumulation of alpha-ketoglutarate was related to the addition of CaCO3.
      Furthermore, it was found that: (1) delaying the addition time of CaCO3 decreased
      the a-ketoglutarate formation but increased C(PYR)/ C(alphaKG); and (2) under
      vitamin limitation conditions increasing the concentration of CaCO3 led to an
      increased a-KG accumulation at the expenses of pyruvate. To study which ions in
      CaCO3 was responsible for the accumulation of alpha-KG, the effects of different
      pH buffers on the a-KG accumulation were studied. The level of alpha-KG was found
      to correlate with the levels of both Ca2+ and CO3(2-), with Ca2+ played a
      dominant role and CO3(2-) played a minor role. To find out which pathway was
      responsible for the accumulation of alpha-KG, the effects of biotin and thiamine
      on alpha-KG accumulation was investigated. The increase in biotin concentration
      led to an increase in alpha-KG accumulation and a decrease in C(PYR)/ C(alpha
      KG), while the levels of alpha-KG and C(PYR)/C(alphaKG) were not affected by
      thiamine concentration. The activity of pyruvate carboxylase was increased as
      much as 40% when the medium was supplemented with Ca2+ . On the other hand, the
      activity of the pyruvate dehydrogenase complex was unaffected by the presence of
      Ca2+. To conclude, the higher level of a-KG was caused by higher activity of
      pyruvate carboxylase stimulated by Ca2+, with CO3(2-) served as the substrate of
      the reaction.

PMID- 15971593
TI  - [Flow model of internal-loop granular sludge bed nitrifying reactor].
AB  - Internal-loop granular sludge bed nitrifying reactor is a new type of aerobic
      nitrifying equipment and has shown a good potential for nitrification. To study
      the flow pattern and construct the flow model, the tracer tests were performed
      using pulse stimulus-response technique. Based on the experimental results, the
      flow pattern in the settling section and the circulating section of reactor were
      analyzed by axial dispersion model and tank-in-series model, respectively. The
      dispersion number D/uL of 0.00148 in the settling section indicates that its flow
      pattern is similar to plug flow reactor (PFR), and the series number N of 1.021
      in the circulating section indicates that its flow pattern is similar to
      continuously stirred tank reactor (CSTR). During steady state, the theoretic
      hydraulic retention time is 360 min, and the actual hydraulic retention time is
      341.2 min. The percentage of dead space in the reactor is 5.22%, thereinto the
      dead space caused by biomass (db ) is 0.75 % and the hydraulic dead space (dh) is
      4.47%, which shows that the structural performance of the reactor is excellent.
      Based on the experiments and analysis, a model of CSTR and PFR in series was
      constructed. The actual hydraulic retention time distribution of the reactor is
      in good agreement with the model predictions. Since the relative error between
      them is 8.56%, the model is accurate to describe the flow pattern. The results
      have laid a foundation for the kinetic model of the reactor and will be helpful
      for its design and operation.

PMID- 15971592
TI  - [The construction and expression of superantigen SEA and antimelanoma ScFv fusion
      gene].
AB  - Two strategies, direct ligation after enzyme digestion and over-lap PCR
      technology, were adopted to construct a fusion gene which was composed of the
      antimelanoma single chain antibody gene and the staphylococcal enterotoxin A gene
      without N-terminal signal sequence. The fusion gene was subcloned into pET28-a
      vector and transformed into E. coli BL21(DE3). Ni-NTA system was selected to
      separate and purify the expresstd products. The inhibition ratio of the fusion
      protein was tested by MTT method. It is shown that the 6His-ScFv-SEA fusion
      protein can be expressed stably in E. coli BL21 (DE3). The quantity of the fusion
      protein was shown up to 30% of the total protein of the bacteria and mainly in
      inclusion body. By activation the effective cells, the fution protein can inhibit
      the melanoma cell whith expressed corresponding antigen.

PMID- 15971594
TI  - [Expression of recombinant human zona pellucida-3 protein (rhZP3) in Pichia
      pastoris].
AB  - Human Zona Pellucida(ZP), which is a complex matrix surrounding oocytes,is
      comprised of three immunologically distinct glycoproteins(hZP1, hZP2 and hZP3).
      Because hZP3 possesses the sperm receptor activity and the acrosome-inducing
      activity, it has long been used as a candidate antigen to develop an
      immunocontraceptive vaccine. However, a large amount of native hZP3 protein is
      unavailable. It is an effective way to express hZP3 protein directly in vitro.
      Nevertheless, it had been reported that the rhZP3 protein produced in Pichia
      pastoris was not secreted but accumulated in the cells and could only be purified
      after being solubilized by strong denaturants. More unfortunately, after
      purification the final product required 6mol/L urea to maintain solubility. An
      improved project was advanced with the aim to express secreted and soluble rhZP3
      protein in yeast. In this study, the fragment of hZP3 cDNA coding for aa 23 -
      408, which the N-terminal leader was removed and most of the C-terminal
      transmembrane-like domain was reserved, was amplified by two PCR primers
      including EcoR I and Not I sites respectively and a His6 codon cassette was added
      to 5'-terminal. The hZP3 insert was incorporated into expression vector pPIC9K.
      The resulting recombinant yeast expression vector was designated pPIC9K-rhZP3.
      Linearized pPIC9K-rhZP3 was transformed into Pichia pastoris. After G418
      selection, the recombinant Pichia pastoris strains were identified by PCR and the
      rhZP3 was expressed following the manufacturer' s protocol. Following induction
      with methanol, the rhZP3 protein was secreted and dissolved into the culture
      supernatant. SDS-PAGE and Western blot analyses showed that the apparent
      molecular weight of the expressed rhPZ3 proteins in yeast was smaller and a
      little size heterogeneity than native ones; after purified with Ni-chelating
      affinity chromatography, the final product's apparent molecular weight was about
      32 - 34KD and their yield more than 20mg/L. We supposed that the C-terminal
      transmembrane-like domain be useful for secretion of rhZP3 into the culture
      supernatant and the expressed rhZP3 protein be incompletely digested by
      proteinases of Pichia into shorter fragments which all were glycosylated
      inhomogeneously. Fortunately, the fragments of rhZP3 protein can be recognized in
      Western blot by the polyclonal antibodies to porcine ZP3 which has showed a cross
      reactivity with human ZP in vitro. It will be expected that the rhZP3 protein
      expressed in Pichia pastoris not only has immunogencity, say, it can rise
      antibodies in vivo to prevent spermatozoa-ovum binding, but also does not contain
      ovarian factors that might be the cause of undesired side effects, e.g. ovaritis
      and can be used as a safe immunogen in human antifertility vaccine research.

PMID- 15971595
TI  - [Chemical induction -- new strategy of oocyte enucleation].
AB  - Mammalian somatic cloning has got great progress during past few
      years,however,the efficiency of nuclear trasfer remains low. In order to improve
      this technique, different perspectives of which are studying. Accordingly, the
      method of oocyte enucleation also becomes a focus. But the physical enucleation
      is technically demanding, time-consuming, inherently invasive and clearly
      damaging to cytoplast spatial organization. As a alternative strategy to
      traditional method, Demecolcine-induced enucleation(IE) attracted the scientist's
      eyes. Nuclear transfer procedure assited with IE, factors releated with success
      rate of IE and effects of IE on the oocytes and cloned embryos are mainly
      discussed in this review. At the same time, combining with author's research, the
      existing problems of IE and potential improved measures of some key steps in IE
      procedure are also elucidated. However, the utility of the demecolcine-induced
      enucleation protocol will require further deep investigation.

PMID- 15971596
TI  - [Production of mammary gland bioreactor by gene targeting of somatic cells].
AB  - Producing mammary gland bioreactor showed great advantage over many years, but
      the level of transgenic expression was low in transgenic animals and the
      diversity was more great because of the position effect of transgene and the
      artificial recombination of the gene elements. Gene targeting based on the
      principle of gene homologous recombination had been studied and applied, because
      the transgene could be integrated precisely in the chromosome. This review
      summary the current status of producing mammary gland bioreactor by the
      technology of gene targeting and nuclear transfer using the somatic cell lines.
      These aspects were discussed, including the characteristic and difficulties of
      gene targeting, the strategies to improve the efficiency of gene targeting, the
      different features of between the strategy of promoter-trap and the Cre-LoxP
      system, etc; for the others, how to select the cell lines with the different
      strategies of gene targeting, how to raise the times of cell lines that was
      cultured after the gene targeting. Somatic cell nuclear transfer offers new and
      exciting opportunities in the areas of the gene targeting. However, the field as
      a whole is still difficult and complex. In this paper, we described recent
      advances and novel approaches, which resulted in progress during the last year.
      Key problems hindering further progress are addressed, for example, how to
      increase the efficiency of nuclear transfer. With the technology of gene
      targeting and nuclear transfer, it should provide a general way to produce
      specific genetic changes in several mammalian species. We are clearly at the dawn
      of a new era in mammalian genetic technology.

PMID- 15971597
TI  - [The reverse genetics systems for human and animal RNA viruses].
AB  - The recovery of the virus from genetic materials in in vitro culture systems or
      sensitive animals is called virus rescue. A functional infectious clone of RNA
      virus provides unlimited possibility for genetic studies and the related reverse
      genetics system that allows directed genetic manipulation of an RNA virus is an
      extremely powerful research tool. In the past twenty years, especially since the
      first infectious clone of a negative-stranded RNA virus was reported in the mid
      1990's, the reverse genetics systems have been available for nearly all the major
      human and animal RNA virus groups. The article reviews the progress of this
      technology, highlighting the obstacles in the construction of reverse genetics
      systems for major groups of human as well as animal RNA viruses and how the
      virologists overcame them. There are mainly four external expression systems for
      construction of the RNA virus reverse genetics systems basing on the kind of RNA
      viruses. These systems include in vitro RNA transcripts, RNA polymerase I-driven
      expression plasmids, RNA polymerase II-driven expression plasmids and modified
      vaccinia virus/T7 RNA polymerase-driven expression system. In particular, the
      viral nucleoprotein and polymerase proteins are required to assemble the viral
      ribonucleoprotein (RNP) complexes for the rescue of the negative-stranded RNA
      viruses. Relevant topics about the rescue of the typical viruses are discussed,
      including poliovirus with the de novo synthesis, Coronaviridae with the largest
      size of genome, Flaviviridae with the instable clones, HCV with the quasispecies
      nature, nodaviruses with the virus-host interaction, influenza virus with the RNA
      pol I transcription system, Arenavirdae with the ambisense coding strategies etc.

PMID- 15971598
TI  - [Progress on molecular biology of delta6-fatty acid desaturases].
AB  - Polyunsaturated fatty acids (PUFAs) including gamma-linolenic acid are valuable
      products because of their involvement in several aspects of human health care.
      GLA has been claimed to play a crucial role in development and prevention of some
      skin diseases, diabetes, reproductive disorder and others. At present, market
      demand for most gamma-linolenic acid is growing continually and current sources
      are inadequate for satisfying this demand due to the significant problems of low
      productivity, complex and expensive downstream process and unstable quality.
      Therefore, seeking for alternative sources are demanding. delta6-fatty acid
      desaturase is the rate-limiting enzyme for the biosynthesis of PUFAs, which
      catalyses the conversion of linoleic acid and alpha-linolenic acid to gamma
      linolenic acid and stearidonic acid respectively. Unfortunately, the structure
      information on membrane desaturases is scarce because of the technical
      limitations in obtaining quantities of purified protein and the intrinsic
      difficulties in obtaining crystals from membrane proteins. With the isolation of
      the genes coding for delta6-fatty acid desaturase from various organisms, its
      characteristics will be elucidated gradually. Here we concisely reviewed the
      recent progress on studies of molecular biology including the cloning of delta6
      fatty acid desaturase gene, structure and function, phylogeny and prospects of
      gene engineering application.

PMID- 15971599
TI  - [Application of bioinformatics in researches of industrial biocatalysis].
AB  - Industrial biocatalysis is currently attracting much attention to rebuild or
      substitute traditional producing process of chemicals and drugs. One of key
      focuses in industrial biocatalysis is biocatalyst, which is usually one kind of
      microbial enzyme. In the recent, new technologies of bioinformatics have played
      and will continue to play more and more significant roles in researches of
      industrial biocatalysis in response to the waves of genomic revolution. One of
      the key applications of bioinformatics in biocatalysis is the discovery and
      identification of the new biocatalyst through advanced DNA and protein sequence
      search, comparison and analyses in Internet database using different algorithm
      and software. The unknown genes of microbial enzymes can also be simply harvested
      by primer design on the basis of bioinformatics analyses. The other key
      applications of bioinformatics in biocatalysis are the modification and
      improvement of existing industrial biocatalyst. In this aspect, bioinformatics is
      of great importance in both rational design and directed evolution of microbial
      enzymes. Based on the successful prediction of tertiary structures of enzymes
      using the tool of bioinformatics, the undermentioned experiments, i.e. site
      directed mutagenesis, fusion protein construction, DNA family shuffling and
      saturation mutagenesis, etc, are usually of very high efficiency. On all
      accounts, bioinformatics will be an essential tool for either biologist or
      biological engineer in the future researches of industrial biocatalysis, due to
      its significant function in guiding and quickening the step of discovery and/or
      improvement of novel biocatalysts.

PMID- 15971600
TI  - [XBP-1 interacts with estrogen receptor alpha (ERalpha)].
AB  - Estrogen receptor alpha (ERalpha) has been a primary target of treatment as well
      as a prognostic indicator for breast cancer. The level of human X-box binding
      protein 1 (XBP-1) mRNA was related with that of ERalpha in breast tumors and was
      over-expressed in some breast tumors. These previous studies suggested that XBP-1
      may interact with ERalpha. XBP-1 has two isoforms, XBP-1S and XBP-1U, as the
      result of unique splicing. GST pull-down assay showed that both XBP-1S and XBP-1U
      bound to ERalpha in vitro. The binding of XBP-1S to ERalpha was stronger than
      that of XBP-1U to ERalpha. Co-immunoprecipitation revealed that the binding was
      in a ligand-independent manner. XBP-1S and XBP-1U interacted with the region of
      ERalpha that contains a DNA-binding domain. The ERalpha-interacting regions on
      XBP-1S and XBP-1U have been mapped to two regions, the N-terminal basic region
      leucine zipper domain (bzip) and the C-terminal activation domain. These findings
      suggest that XBP-1S and XBP-1U may participate in ERalpha signaling pathway
      through the mediation of ERalpha.

PMID- 15971601
TI  - [Construction of recombinant fowlpox virus coexpressing gp120 of Chinese HIV-1
      strain and IL-18 and its immunogenicity in mice].
AB  - To screening out Chinese vaccine candidate against HIV-1, Chinese vaccine strain
      282E4 of fowlpox virus was used as the vector to construct the recombinant
      fowlpox virus (rFPV) coexpressing gp120 of Chinese HIV-1 strain and IL-18, and
      the recombinant virus was indentified by PCR and Western blot. The specific DNA
      fragment could be amplified by PCR from the genome of rFPV. Western blot analysis
      showed that gp120 and IL-18 could be expressed not only in chicken embryo
      fibroblast (CEF) cells infected by rFPV, but also in mammalian cells infected by
      rFPV. After the recombinant fowlpox virus was inoculated into BALB/c mice, the
      spleen specific CTL activities and serum antibodies in the immunized mice were
      detected, which demonstrated that the rFPV had good immunogenicity and could
      induce BALB/c mice to produce specific humoral and cellular immunity. IL-18
      palyed the role of immunoadjuvant. The study lays the basis on the preparation of
      genetic engineering live vector vaccine against HIV-1.

PMID- 15971602
TI  - [Soluble expression and target study to brain of anti-TfR ScFv].
AB  - The single-chain antibody gene (ox26-scFv) to transferrin receptor (TfR) was
      synthesized and amplified by three-step PCR. After sequencing, the gene was
      cloned into prokaryotic expression vector pTIG-Trx which carried thioredoxin
      (Trx) gene and a C-terminal His.tag. The Ox26-scFv proteins achieved 31% yields
      of total bacteria proteins at 20 degrees C, after 0.02mM IPTG induction using the
      strain E. coli BL21 (DE3). The soluble scFv proteins in cytoplasm suspension were
      about 35% and the inclusion bodies were about 65%. The soluble products were
      purified by immobilized metal chelation affinity chromatography (Ni-NTA), a
      single band with molecular weight 29 kD appeared on SDS-PAGE gel. Rat GH3 cell
      immunocytochemistry staining showed that Ox26-scFv protein could recognize and
      bind to transferrin receptor. Injected SD rats with Ox26-scFv proteins by tail
      veins, the antibodies were detected from brain tissues specially on the brain
      capillaries 4 h later which indicate that Ox26-scFv proteins have a good target
      function to brain capillaries and can permeate the blood-brain barrier mediated
      by the transferrin receptors.

PMID- 15971603
TI  - [Studies of the expression, purification, renaturation and biologic activity of
      an anti-CEA immunotoxin].
AB  - A recombinant immunotoxin named CEA/PE38/KDEL was constructed, which was composed
      of anti-CEA single-chain Fv and the truncated and modified form of Pseudomonas
      exotoxin (PE38/KDEL). The CEA/PE38/KDEL immunotoxin was expressed in the E. coli
      strain BL21 (DE3)-star as inclusion bodies. The denatured inclusion bodies were
      purified with Ni-NTA chelate agarose, then the constant gradient dialysis was
      used to perform the refolding of the CEA/PE38/KDEL immunotoxin. Results of FACS
      and MTT assay indicate that the refolded immunotoxins keep potent and specific
      cytotoxicity to tumor cells bearing CEA antigens.

PMID- 15971604
TI  - [Functional expression of DNA binding domain of Zif268 in Escherichia coli].
AB  - As the ubiquitous nucleic acids recognizing motif, Zinc finger protein play
      important role in regulation of gene expression. The study of recognization
      specific will greatly facilitate understanding the delicate interaction of Zinc
      finger protein and DNA. By the choice of expression vector, the induction and
      culture conditions, the DNA binding domain of Zif268 was expressed in Escherichia
      coli partly solubly. The gel mobility shift assay shows that purified DNA binding
      domain can bind its natural target sequence specifically, which indicates the DNA
      binding domain remains its DNA binding activity in Escherichia coli. The
      functional expression of DNA binding domain of Zif268 will greatly facilitate the
      development of in vivo genetic selection assay for the study of Zinc fingers-DNA
      interaction.

PMID- 15971605
TI  - [Screening serum response special antibodies of U251 cell line from surface
      display phage antibody library].
AB  - U251 cell is a sensitive cell line to serum, which stops at G0 phase of cell
      cycle in no-serum medium, and recovers growth when the serum is added into no
      serum medium. The cell can express corresponding proteins in different phase of
      cell cycle. Therefore it is very signification for the study of cell cycle
      regulation mechanism that explores these proteins. In this paper, the mouse
      antibody phage display library was added into the bottle in which the serum
      starvation U251 cells had been cultured, and the special antibody phages were
      absorbed. Then the absorbed antibody phages were amplified by adding E. coli TG1
      and helper phage M13K07. Amplified antibody phages were added into bottle in
      which the serum cultured cell after serum starvation (follow named as serum
      recovered cells) were incubated, so that the cell absorbed the no-special
      antibody phages for the serum starvation cell and the special antibody phages
      were in supernatant. The remaining no-special antibody phages in the supernatant
      were discarded by repeating above program 3-4 times. The pure special antibody
      phages were gotten, and amplified by adding the host cell E. coli TG1 and helper
      phage M13K07. Then the host bacterium infected special antibody phage was spread
      on the plate medium with ampicillin, and the monoclonal antibody phages were
      gotten. Using same as above program, the monoclonal antibody phages absorbed
      specially for serum recovered U251 cells were obtained when the serum recovered
      cells instead of serum starvation cells and serum starvation cells instead of
      serum recovered cells. In this study, ninety-six positive monoclonal antibody
      phages that absorbed specially the serum starvation cells and eighty-two positive
      monoclonal antibody phages that absorbed specially the serum recovered cells were
      obtained. By using cell immunochemistry assay, two special signification
      antibodies were obtained. one (No.11) was the strong response in serum starvation
      cells, the other (No.2) was the strong response in serum recovered cells. The
      antibody No.2 had the distinctive response to the serum recovered cells in
      different incubation time (15min, 30min, 1h, 2h, 4h, 8h, 12h and 48h) after serum
      starvation. The results showed that No.2 antibody would be useful to research the
      factors of cell cycle regulation and apply to tumor diagnosis.

PMID- 15971606
TI  - [The ht-PAm cDNA knock-in the goat beta-casein gene locus].
AB  - The production of recombinant protein is one of the major successes of
      biotechnology, animal cells are required to synthesize proteins with the
      appropriate post-translational modifications. Transgenic animal mammary gland
      bioreactor are being used for this purpose. Gene targeting is a more powerful
      method to produce mammary gland bioreactor, and nuclear transfer from cultured
      somatic cells provides an wonderful means of cell-mediated transgensis. Here we
      describe efficient and reproducible gene targeting in goat fetal fibroblasts to
      place the human tissue plasminogen activator mutant (ht-PAm) cDNA at the beta
      casein locus, and would produce the transgenic goat by nuclear transfer. To
      construct the gene targeting vector pGBC4tPA, the milk goat beta-casein genomic
      DNA sequence for homologous arms had been cloned firstly. The left arm was 6.3 kb
      fragment including goat beta-casein gene 5' flanking sequence, and the right arm
      was 2.4 kb fragement including beta-casein gene from exon 8 to exon 9. The ht-PAm
      cDNA was subcloned in the goat beta-casein gene exon 2, and the endogenous start
      condon was replaced by that of ht-PAm. The bacterial neomycin (neo) gene as
      positive selection marker gene, was placed in the beta-casein gene intron 7, the
      thymidine kinase (tk) as the negative selection marker gene, was just outside the
      right arm. The validity of the positive-negative selection vector (PNS), was
      tested, and targeting homologous recombination (HR) were elevated to 5-fold with
      the negative selection marker using the drug GANC. The DNA fragment in which two
      LoxP sequence was delected effectively using Cre recombinase in vitro. Goat fetal
      fibroblasts were thawed and cultured to subconfluence before transfection, about
      10(7) fibroblasts were electoporated at 240V, 600 microF in 0.8 mL PBS buffer
      containing linear pGBC4tPA. transfected cells were cultured in collagen-coated 96
      wellplate for 24h without selection, then added the drug G418 (600 microg/mL) and
      GANC (2 micromol/L). After 12 days of selection, well separated G418r/GANCr
      clones were isolated and expanded in 24-wellplate. 244 clones were selected, and
      only 90 clones could grow and be tested by PCR screening for targeting. The
      primary result demonstrated that 31 targeting cell clones with homologous
      recombination events were obtained, and 2 cell clones was verified by DNA
      sequence analysis on the homologous recombination region.

PMID- 15971607
TI  - [Establishment of Saussurea involucrata hairy roots culture and plantlet
      regeneration].
AB  - Hairy root clones of Saussurea involucrata transformed with Agrobacterium
      rhizogenes strains R1601, R1000, and LBA9402 were established to investigate the
      flavonoid production. Opine synthesis and PCR analysis confirmed the integration
      of the T-DNA fragment of Ri plasmid from A. rhizogenes strain R1601 into the
      transformed root genome. The frequency of hairy root formation from root
      segments, which were pre-cultured 2 days in N6 solid medium without plant growth
      regulators, amounted to 100% following infection with R1601 strain of A.
      rhizogenes. The transformed roots were kept in hormone-free N6 liquid medium in
      the dark at 25 degrees C, 110r/min and routinely subcultured every 20 - 24 days.
      One hairy root clone, which grew vigorously with lateral branches, was
      periodically examined for the ability to produce flavonoid. The maximum of
      biomass and flavonoid yield achieved 66.7 g/L (fresh weight) and 102.3mg/g dry
      weight after incubation 20 days. The calli were induced from the hairy root
      culture in the presence of 0.5mg/L IBA and intact plantlets were regenerated from
      these calli. The regeneration plantlets from hairy roots, in which the flavonoid
      content were 53% in that of untransformed plants, weren't different in growth and
      morphology of the untransformed plantlets. Therefore plant regeneration from
      hairy roots may be also a means for producing transformed S. involucrata plants.
      Hairy root cultures of S. involucrata clearly showed higher flavonoid contents
      compared to the wild plant or the regeneration seedlings. As the wild S.
      involucrata grows only in special regions with peculiar climate, and cultivation
      of this species in a normal climate has been unsuccessful so far. The success in
      obtaining a method for high production of flavonoid might very well be one of the
      solutions for this problem in the future.

PMID- 15971608
TI  - [Expression of human mu-opioid receptor cDNA in CHO cell].
AB  - Opioid receptor, is classified into three subtypes, mu, kappa and delta, with the
      mu-type receptor plays important roles in opioid analgesia and opioid addiction.
      The cDNA encoding mu-type receptor was obtained by RT-PCR from human brain RNA
      and was cloned into pcDNA3.1(+). The resultant recombinant plasmid pcDNAMORs were
      transfected into CHO cells by liposome. After PCR identification, the positive
      clone were treated with agonist and antiagonist were tested for their competence
      of signal transduction. CHO cells that contained mu-opioid receptor in the
      expression vector pcDNA3.1(+) acquired naloxone-blockable high-affinity specific
      binding of morphine and DAMGO. The concentration of cAMP in CHO cells transfected
      with pcDNAMOR was reduced after binding to morphine and DAMGO, and increased
      after binding naloxone. These results indicate that the mu-type receptor expreesd
      on the CHO cell has similar biological property as the nature receptor. The
      availability of these specific cell lines will facilitate the drug development
      and promote our understanding the mechanism underlying opiate addiction.

PMID- 15971609
TI  - [Expression and purification of heptad repeat region of the mumps virus F protein
      and analysis of characteristics].
AB  - Two Heptad repeat motifs (HR1 and HR2) from paramyxoviruses F protein could form
      thermostable heterodimers containing high alpha-helix while virus infected host
      cell. Following that the viral membrane and the host cell membrane were
      juxtaposed, which leads to membrane fusion. Mumps virus (MuV) is a member of the
      genus Rubulavirus in the family of Paramyxoviridae. MuV could use similar
      infection mechanism as well as other paramyxoviruses. In this study the HR1 and
      HR2 regions of MuV F protein were predicted by a computer program and expressed
      in E. coli with the GST fusion expression system. The GST fusion or GST-removed
      proteins were purified with Gluthathion Sepharose 4B Column. GST pull-down
      experiment suggested the interaction of HR1 and HR2 peptides, and analysis of gel
      filtration showed two peptides could form multimer, which indicates that the HR
      regions of MuV F protein may play an important role in virus fusion.

PMID- 15971610
TI  - [Preparation and characterization of HLA-A * 0201 monomer and tetramer loaded
      with HCMV antigenic peptide].
AB  - Quantification of cytotoxic T lymphocytes (CTL) is extremely important due to the
      pivotal role they play in controlling pathogen infection and anti-tumor actions.
      Previously used methods for detecting specific CTL are usually indirect. In
      recent years, tetramer technology has been developed to directly visualize
      antigen-specific CTL efficiently, and become the critical approach in studying T
      cell immune responses. A simplified procedure for preparing tetramers is reported
      here in this paper and a tetramer loaded with human cytomegalovirus (HCMV)
      peptide was successfully obtained using this procedure, which possessed binding
      activity with specific CTL. The heavy chain of HLA-A * 0201 gene was cloned by RT
      PCR from HLA-A2+ donor. An expression vector, encoding the extracellular domain
      of HLA-A * 0201 heavy chain (A2) fused with a BirA substrate peptide (BSP) at its
      carboxyl terminus, was constructed by PCR with cloned A2 gene as the template.
      The A2 heavy chain was expressed in Escherichia coli mostly in the form of
      inclusion body and purified by washing inclusion body. The monomer of soluble A2
      loaded with peptide was reconstructed by dilution from the heavy chain in the
      presence of light chain beta2-microglobulin and HLA-A2 restricted HCMV pp65(495
      503) peptide (NLVPMVATV, NLV). Refolded A2-NLV monomer was biotinylated with a
      commercial BirA and purified by low pressure anion exchange chromatography on a Q
      Sepharose (fast flow) column. The tetramer was then formed by mixing A2-NLV
      monomer with streptavidin-PE in a ratio of 4:0.8 leading to more than 85%
      multiplication as revealed by SDS-PADE under non-reducing conditions without
      boiling the sample. Flow cytometry analysis indicated that this tetramer could
      bind to specific CTL from HLA-A2+ donor. In conclusion, a simplified procedure is
      established to prepare HLA-A2 tetramer, which may not only facilitate the
      application of tetramer technology for studying specific T lymphocyte immune
      response but A2-NLV itself be applied clinically to monitor CMV-specific CTL in
      stem cell and organ transplantation.

PMID- 15971611
TI  - [Affection of metallothionein-3 to dUTPase's accommodating cellular toxicity of
      dUTP].
AB  - Metallothionein-3 (MT-3), renamed as growth inhibitory factor (GIF), is a brain
      specific member of the metallothionein family. Human dUTPase is a recently found
      protein in brain that can interact with hMT-3. They have the growth inhibitory
      activity on neuron cell by interaction. To study the affection of hMT-3 to
      dUTPase's eliminating the cellular toxicity caused by dUTP, the pSVHA-dUTPase and
      pFLag-hMT-3 genes have been transfected into HEK293 cells. In addition, the
      dUTPase and hMT-3 proteins were expressed in BL21 to study the role of hMT-3 on
      the hydrolyzation of dUTP by dUTPase. The results demonstrate that the cells co
      transfected with dUTPase and hMT-3 genes have more strong resistibility to dUTP
      than the cells transfected only with dUTPase gene. And that the hMT-3 protein can
      accelerate the hydrolyzation of dUTP by dUTPase. All these indicate that hMT-3
      can cooperate with dUTPase to protect better the 293 cells from dUTP. This
      research offered the theoretic elements for the application of hMT-3 and dUTPase
      in chemic cure.

PMID- 15971612
TI  - [Construction of protease resistant mutein of human CNTF and its expression in
      Pichia pastoris].
AB  - AX15 is a mutein of naturally occurring human ciliary neurophic factor (hCNTF),
      with improved biological activity, stability and solubility. AX15 is susceptible
      to protease degradation when expressed in Pichia pastoris. Amino acid sequencing
      revealed the degradation was occurred behind position 12 and 13 amino acid
      residues, which constitute a dibasic site, RR. Based on the substrate specificity
      of KEX2, a KEX2 resistant mutein of AX15-AX15 (R13K) was constructed, in which RR
      was replaced by RK. It was demonstrated that the stability of AX15 (R13K)
      improved significantly, as no degradation was detected even after 120 hours of
      induction. AX15 (R13K) was purified to homogeneity by ultrafiltration and gel
      filtration. TF-1 cell survival bioassay showed AX15 (R13K) had equivalent
      specific activity to AX15. The protease resistant mutein of AX15 may have greater
      in vivo stability and thus have superior therapeutic potential.

PMID- 15971613
TI  - [Preliminary proteome analysis for Saccharomyces cerevisiae under different
      culturing conditions].
AB  - For the investigation of the metabolic regulation of Saccharomyces cerevisiae
      under different culture conditions, the proteins of cell utilizing various carbon
      sources were separated by two-dimensional electrophoresis with immobilized pH
      gradients as the first dimension and SDS-PAGE as the second. Samples were taken
      in the log phase of batch culture using glucose or lactic acid as carbon source,
      while another sample was taken from the broth when glucose was consumed up and
      ethanol accumulated in the previous phase was further metabolized. After
      electrophoresis, the protein spots were detected by silver-stain in a Hoefer
      Automated Gel Stainer with a protein silver staining kit. Silver-stained gels
      were scanned and digitized to create computer images. About 500 protein spots
      were detected by employing the 2D proteome image analysis system Image Master 2D
      Elite and SWISS-2DPAGE proteome database. Most of the protein expressed and
      involved in the glycolysis, pentose phosphate (PP) pathway, anaplerotic pathway,
      as well as TCA cycle were analyzed. The metabolism regulation of protein level
      for Saccharomyces cerevisiae under various carbon sources, as well as during
      different phase of growth, was studied. The expression of several glycolytic
      enzymes (glk, pgi, pgk, eno, pyk) was up-regulated while the expression of
      enzymes in oxidative pentose phosphate pathway (zwf, gnd) was down-regulated when
      ethanol and lactic acid were taken as carbon source. Simultaneously, frucotose
      1,6-biphosphatase was found to be up-regulated due to the gluconeogenic
      requirement. Citrate synthase and Malate dehydrogenase do not exhibit significant
      difference, indicating TCA cycle is necessary when utilizing glucose, ethanol or
      lactic acid as carbon source. Thus, the NADPH loss due to the repressed pentose
      phosphate pathway could be compensated by TCA cycle in cases of ethanol and
      lactic acid. The expression of malic enzyme and isocitrate lyase are activated to
      a large extent when metabolizing ethanol, indicating glyoxylate shunt is
      essential in transferring ethanol to generate four carbon precursors for the
      biosynthesis and the NADP-dependent malic enzyme could also serve as compensation
      mechanism for NADPH loss in this case.

PMID- 15971614
TI  - [Metabolic flux analysis of L-valine fermentation in Corynebacterium glutamicum].
AB  - In industrial fermentation of amino acids the cells are often forced to
      synthesize the biochemicals excessive of their physiological needs. The knowledge
      of metabolic networks and their regulation relevant usually come from biochemical
      research, especially from enzymology, not from engineering study. To enrich the
      knowledge of metabolic sub-network of L-valine syntheses for higher production of
      L-valine, Corynebacterium glutamicum AS1.495 and its genetic derivatives AA361,
      AAT231, AATV341 were used for metabolic flux analysis. AS1.495 is a leucine
      auxotrophic (Leu-), and the three derivatives carry additional mutations. AA361
      contains D-aspartic acid-beta-hydroxamate supersensitive marker (Leu-, L-AAHss),
      AAT231 (Leu-, L-AAHss, 2-TAr) is D-aspartic acid-beta-hydroxamate supersensitive
      and 2-thiazole alanine resistant, and AAT341 (Leu-, L-AAHss, 2-TAr, Vd-) is a D
      aspartic acid-beta-hydroxamate supersensitive, 2-thiazole alanine resistant and
      valine-decompose-ability imperfect (Vd-). The concentrations of extra-cellular
      metabolites were determined under sub-steady-state of the batch culture. The
      metabolic flux distribution maps of the four strains were obtained, compared and
      analyzed. Our analysis showed that the flux ratio of EMP and HMP from the glucose
      6-phosphate had increased from 0.205 in the parental strain AS1.495 to 0.321 in
      the multiple-mutation strain AATV341; the flux ratio of L-valine synthesis branch
      and the rest branches from the pyruvate node increased from 0.188 in AS1.495 to
      3.29 in AATV341; the flux of lactic acid synthesis branch decreased from 11.1 in
      AS1.495 to 1.16 in AATV341; the flux of L-valine synthesis branch increased from
      5.37 in AS1.495 to 37.3 in AATV341; and the productivity of L-valine
      correspondently increased from 4 g/L in AS1.495 to 24.5 g/L in AATV341. These
      results indicate that the introduction of analog supersensitive marker L-AAH55
      and/or analog resistant marker 2-TAr skew the metabolic flux towards the
      formation of L-valine. This study revealed the usefulness of the metabolic flux
      analysis as a tool for verification of existing production strains. The analysis
      may play an important role in helping us b to rationally re-design metabolism for
      further improvement of fermentation process.

PMID- 15971615
TI  - [High-cell density cultivation of recombinant Escherichia coli for production of
      TRAIL by using a 2-stage feeding strategy].
AB  - Escherichia coli was genetically engineered to produce recombinant tumor necrosis
      factor-related apoptosis inducing ligand (Apo2L/TRAIL) using a temperature
      inducible expression system. To create a fed-batch culture condition that allows
      efficient production of TRAIL, different feeding strategy including
      discontinuous, DO-stat and pH-stat feeding strategies were compared. Then, a
      special 2-stage feeding strategy was developed. High concentration of biomass
      (300g wet cell weight per liter of culture broth) and active soluble TRAIL
      protein (1.1g/L) was obtained by applying a high-cell-density cultivation
      procedure with the 2-stage feeding strategy. Cultivation of recombinant E. coli
      was started as a batch process at 30 degrees C and then followed by fed-batch
      culture when the dissolved oxygen concentration presented a steep increase
      resulted from the exhaustion of glucose in the medium. At the first phase of
      fermentation (batch phase), agitation rate was enhanced to control dissolved
      oxygen at 30 percent. When glucose in the medium was used up, indicated by a
      sudden rise in pH value and dissolved oxygen, the second phase (fed-batch phase)
      was started with glucose and nitrogen resource being supplied automatically. At
      the beginning of fed-batch operation, stirrer rate was cascaded with dissolved
      oxygen signals to keep it at 20 percent (DO-stat). During the fed-batch phase,
      glucose was limited to control the specific growth rate under the critical value
      microcrit, to avoid acetic acid excretion. When the stirrer speed arrived at its
      up-limit, the flow rate of feed was kept constant. In the inducing phase(42
      degrees C for 4h) glucose was fed as a pH regulating agent (pH-stat) and the
      specific growth rate and dissolved oxygen decreased sharply. Aqueous ammonia was
      used for maintaining pH value at 7.0 throughout the first two phases. In the
      whole fermentation, acetic acid concentration didn't exceed 2.9 g/L. At the end
      of the high-cell-density cultivation process, no acetic acid could be detected in
      the medium. These results indicated that our fed-batch strategy was able to
      prevent acetate accumulation significantly. Although high cell density has been
      achieved, the induction process was not optimized satisfactorily and much work
      should be done further. Furthermore, since no special ways, like pure oxygen,
      pressure, has been used in our experiments, this efficient approaches would be
      useful not only in a pilot scale but also in an industry scale. Finally, simple
      purification procedure based on immobilized metal affinity column (IMAC) and CM
      Sepharose column was implemented to isolate the TRAIL. Yields of more than 800mg
      TRAIL per liter of culture broth were obtained, the final purity reaching more
      than 95%. The purified TRAIL showed strong cytotoxity activity against human
      pancreatic 1990 tumor cells, with ED50 about 1.6 microg/mL.

PMID- 15971616
TI  - [Media optimization for exopolysaccharide by Pholiota squarrosa (Pers. ex Fr.)
      Quel. AS 5.245 on submerged fermentation].
AB  - Our previous work has indicated that mycelium growth and exopolysaccharide
      accumulation in submerged fermentation by Pholiota squarrosa (Pers. ex Fr.) Quel.
      AS 5.245 are strongly affected by many internal and external factors, including
      medium constituents and fermentation conditions. In this study, we use an
      effective two-phase statistical approach to enhance exopolysaccharide production.
      In the first phase, Plackett-Burman design was undertaken to evaluate the effects
      of the twenty factors, i.e., glucose, fructose, maltose, yeast extract, tryptone,
      K2HPO4, KH2PO4, (NH4)2SO4, NaNO3, FeSO4, MgSO4, MnCl2, ZnCl2, FeCl3, CuSO4.5H2O,
      vitamin B1, initial pH, the temperature, the medium volume and the duration, to
      the fermentation. By regression analysis, yeast extract, tryptone, fructose,
      MgSO4, MnCl2, initial pH and temperature were found to be important for
      exopolysaccharide production, while glucose, maltose, NaNO3, ZnCl2, vitamin B1,
      the duration and the volume are important to the mycelium biomass. In the second
      phase of the optimization process, a response surface methodology (RSM) was used
      to optimize the above critical internal factors, and to find out the optimal
      concentration levels and the relationships between these factors. Based on the
      results of the first phase, a five-level six-factor (yeast extract, fructose,
      MgSO4, maltose, ZnCl2 and initial pH) central composite rotatable design (CCRD)
      was employed. By solving the quadratic regression model equation using
      appropriate statistic methods, the optimal concentrations for obtaining 876.32
      microg exopolysaccharide per milliliter of fermentation liquor were calculated
      as: 6.0g/L yeast extract, 11.5g/L fructose, 0.5g/L MgSO4, 9.6g/L maltose,
      38.6mg/L ZnCl2 and with the initial pH 5.3. The experimental data under various
      conditions have validated the theoretical values.

PMID- 15971617
TI  - [Thermo-alkali-stable catalase from Thermoascus aurantiacus and its potential use
      in textile bleaching process].
AB  - The effect of growth and fermentation conditions on the production of catalase by
      T. aurantiacus WSH 03-01 was investigated in shaking flasks. Catalase activity
      reached 1594 u/mL when the culture was grown on a complex carbon source
      containing 20 g/L dextrin and 1% (V/V) ethanol, which was 23% higher than the sum
      produced on 20 g/L dextrin and 1% (V/V) ethanol, respectively. It was concluded
      that dextrin might act as a major carbon source in the complex, while ethanol was
      rather a stimulator than a carbon source. The stimulation effect of ethanol on
      catalase production was postulated to be two aspects; catalase-dependent alcohol
      metabolism is activated by acute alcohol, thus more catalase need to be
      synthesized for that use, named direct induction. As for indirect induction,
      which may result from little amount of H2O2 generation in process of NADH
      regeneration in respiratory chain. Peptone was shown to be a favorable nitrogen
      source for catalase production and its optimum concentration was found to be 10
      g/L. Catalase production by T. aurantiacus WSH 03-01 was further improved by
      optimizing the initial pH, volume of medium in flasks as well as the
      concentration of external H2O2. Under the optimum culture conditions, the
      activity of catalase reached 2762 u/mL, which was nearly 6.8 times higher than
      that of the initiate conditions. Furthermore, the potential application of this
      novel catalase in the treatment of textile bleaching effluents was evaluated.
      Thermo-and alkaline stability of this catalase was compared with the commercial
      available catalases produced from bovine and Aspergillus niger. The crude enzyme
      from T. aurantiacus WSH 03-01 showed stronger stabilities at (70 degrees C, 80
      degrees C, 90 degrees C) and (pH 9.0, pH 10.0, pH 11.0) than the other two types
      of catalases, indicating a great application potential in the clean production
      process of textile industry.

PMID- 15971619
TI  - [Isolation of thermophilic bacteria Thermus sp. YBJ-1 and cloning of amylase
      gene].
AB  - Thermophilic bacteria strain YBJ-1 was isolated from hot spring samples collected
      from Yangbajing, Tibet. The 16sr DNA sequence of YBJ-1 (1511bp in length) shares
      98% identity with that of Thermus scotoductus strain ITI-252T. The full-length
      ORF of amylase gene of YBJ-1 (amyT) was amplified by PCR technique and cloned
      into T-vector. The complete sequence of amyT is 1767bp in length, coding for 588
      amino acids. The deduced amino acids share 99% similarity with alpha
      cyclodextrinse of Bacillus sterothermophilus, 96% with maltogenic amylse of
      Thermus. sp IM6501, and 81% with neopullulanase of Bacillus sterothermophlus.

PMID- 15971618
TI  - Thiocyanate elution measurement of relative affinity of phage antibodies.
AB  - Human antibodies generated by phage antibody technology have been widely used in
      the immunotherapy of various diseases. Among the characteristics of these
      therapeutic antibodies, affinity is one of the most important determinants of
      their biological efficacy. The binding of an antibody and its corresponding
      antigen could be disrupted by thiocyanate solution of different concentrations,
      depend upon the affinity of the antibody. This mechanism has been adopted to
      determine the relative affinity of monoclonal or polyclonal antibodies in routine
      immunological practice. Correlation between the elution method and other
      techniques that measure the affinity such as equilibrium dialysis and biospecific
      interaction analysis (BIA) has been established. Here we describe the
      applications of the thiocyanate elution method in the determination of the
      relative affinity index (RAI) of phage antibodies (Phabs). Five clone antibodies,
      including 3 clones of anti-keratin antibodies (AK1, AK2 and AK3) and 2 clones of
      anti-HBsAg antibodies (HB1 and HB2) were selected to express Phabs and Fabs, and
      the RAI were determined by ELISA after thiocyanate elution. A HRP-conjugated anti
      M13 was used as secondary antibody for Phabs and HRP-goat-anti-human Fab was used
      for Fabs. The affinity ranks of the Phabs were compared with that of the Fab
      fragments. The results showed that all the Phabs tested were tolerant to
      thiocyanate treatment. The relative affinity rank of 5 Phabs coincided well with
      that of their corresponding Fabs. We conclude that the thiocyanate elution can be
      used as an easy and rapid method to measure and compare the relative affinity of
      Phabs.

PMID- 15971620
TI  - [Expression of the infectious bursal disease virus polyprotein in Vero cells
      using attenuated Salmonella typhimurium as transgenic carrier].
AB  - To examine if polyprotein gene (VP2/VP4/VP3) of Infectious Bursal Disease Virus
      (IBDV) could be delivered into mammalian cells and expressed using attenuated
      Salmonella typhimurium as vector. The IBDV polyprotein gene was amplified by RT
      PCR and inserted in to pCI, an eukaryotic expression plasmid. The resulting
      recombinant pCI-VP2/VP4/VP3 was transformed by electroporation into attenuated
      Salmonella typhimurium strain ZJ111 (dam- and phoP-), which was then use to
      transfect the Vero cells. Gene specific RT-PCR revealed that VP2/VP4/VP3 was
      transcribed into mRNA in the Vero cells. Indirect immunofluorscence assay, SDS
      PAGE and Western-blot analysis showed that VP2/VP4/VP3 was expressed and the
      product was immuno-reactive with anti-IBDV serum. This work provides essential
      precondition for developing a new oral DNA vaccine against IBDV.

PMID- 15971621
TI  - [Enhanced ergosterol production by recombinant Saccharomyces cerevisiae 1190
      harboring Vitreoscilla hemoglobin gene (vgb)].
AB  - Ergosterol is a principal sterol of fungi. It is a raw material for production of
      vitamin D2, hydrocortisone, progesterone and brassinolide. Synthesis of
      ergosterol requires molecular oxygen, and low oxygen tensions was reported to
      dramatically reduce ergosterol concentration. Vitreoscilla Hemoglobin Gene (vgb),
      a homodimeric hemoglobin gene from Gram-negative obligate aerobic bacterium
      Vitreoscilla, enables a higher specific cellular oxygen uptake rate, it also
      improves the oxygen transportation. In this study, recombinant plasmid pVgb
      kanMX4 containing Vitreoscilla Hemoglobin Gene (vgb) and geneticin (G418) was
      constructed and transformed into Saccharomyces cerevisiae 1190 for enhanced
      ergosterol production. With sufficient oxygen supply, the ergosterol contents of
      recombinant and wild type strains grown in shake flasks were 1.07% and 0.573%,
      respectively. Under oxygen limitation condition, ergosterol contents in
      recombinant and wild type strains were reduced to 0.39% and 0.25%, respectively.
      In a 30 hours fermentation study conducted in a 5 liter fermentor, 15.1 g/L Cell
      Dry Weight (CDW) containing 1.38% ergosterol was obtained from growth of the
      recombinant strains; Only 14.8 g/L CDW containing 0.9% ergosterol was produced by
      the wild type strain. These results demonstrated that vgb played a role in
      enhancing ergosterol production.

PMID- 15971622
TI  - [Studies on the cell growth, differentiation and terpene lactone accumulation in
      Ginkgo biloba cell suspension cultures].
AB  - To provide supports for Ginkgo biloba cell engineering for production of Terpene
      lactones (Ginkgolides and bilobalide), the cell suspension were established from
      calli induced from zygote embryos and stems of 30-day-old seedlings respectively.
      The relationship between cell growth, differentiation and the terpene lactone
      accumulation in these suspension cultures were investigated. HPLC determination
      indicated that, the ginkgolide B was found in the embryo derived cell suspension
      cultures at 0.044% of cell dry weight, and this result was the first time
      reported in this study. The accumulation of terpene lactone in the suspension
      cultures derived from both the embryo and seedling stems are effected by the
      level of the cell differentiation. The ginkgolide B was only found in small cell
      aggregates in the size smaller than 2mm, and the highest level of ginkgolide B
      was accumulated in cell aggregates in the size smaller than 1mm; however, the
      cell aggregates in the size bigger than 3mm could only produced bilobalide and
      ginkgolide A. In the same size aggregates of the suspension cultures the terpene
      lactone accumulation is strongly effected by the source of the explant. When the
      size of cell aggregates was in less than 1mm, the concentration of bilobalide,
      ginkgolide A and B in the cell suspension cultures derived from the embryos was
      2, 1.4 and 0.56-fold, respectively, higher than that of cell cultures derived
      from seedling stems.

PMID- 15971623
TI  - [Hepatitis E virus capsid protein production by high cell density culture of
      recombinant Escherichia coli].
AB  - Production of Hepatitis E Virus capsid protein by high cell density culture in
      recombinant E. coli has been studied in 10L and 30L fermentors. The effects of
      different factors on growth and producing recombinant protein of E. coli have
      been studied by batch culture, such as different media, the ratio of phosphate
      and Magnesium sulfate. Comparison of fermentation performance for recombinant E.
      coli in different fed-methods culture has been investigated by fed-batch culture.
      The effects of inducing at different stages of growth and time of inducing on
      growth and producing recombinant protein, also obtained by fed-batch culture. At
      last, the solubility of inclusion body in different urea concentrations also has
      been obtained by fed-batch culture. The results show that the concentration of
      phosphate and Magnesium sulfate in the optimal media is 80mmol/L and 20mmol/L in
      batch culture respectively, that induction with 1.0mmol/L IPTG at mid log phase
      (about 45 OD at 600nm) is suitable for growth and recombinant protein expression,
      the cells were approaching stationary growth phase and the maximum cell OD at
      600nm of 80 was achieved in 5h of fed-batch culture, and the expression level is
      29.74%. The results also indicate that the solubility of inclusion body in 4mol/L
      urea solution induced at 37 degrees C reaches 14mg/mL, over 80% inclusion body
      was resolved. The culture process achieved in 10L fermentor could be successfully
      scaled up to 30L fenmentor with good reproducibility.

PMID- 15971624
TI  - [High efficiency of L-glutamine production by coupling genetic engineered
      bacterial glutamine synthetase with yeast alcoholic fermentation system].
AB  - Glutamine is an important conditionally necessary amino acid in human body. The
      effort is to establish a new and high efficient L-glutamine production system
      instead of traditional fermentaion. In this paper, high efficiency of L-glutamine
      production is obtained by coupling genetic engineered bacterial glutamine
      synthetase (GS) with yeast alcoholic fermentation system. Glutamine Synthetase
      gene (glnA) was amplified from Bacillus subtilis genomic DNA with primers
      designed according to sequences reported in EMBL data bank, then it was inserted
      into expression vector PET28b, the sequence of glnA was proved to be the same as
      that reported in the data bank by DNA sequencing. After transformation of this
      recombinant plasmid PET28b-glnA into BL-21 (DE3) strain, Lactose and IPTG were
      used to induce GS expression at 37 degrees C separately. Both of them can induce
      GS expression efficiently. The induced protein is proved to be soluble and
      occupies about 80% of the total proteins by SDS-PAGE analysis. The soluble GS was
      purified by Ni2+ chelating sepharose colum. After purification, the purified
      enzyme was proved active. Results reveal that the optmum temperature of this
      enzyme is 60 degrees C and optmum pH is 6.5 in biosynthetic reaction by using
      glutamate, ammonium choloride and ATP as substrates. After induction, the enzyme
      activity in crude extract of BL-21/PET28b-glnA is 83 times higher than that of
      original BL-21 extract. Mn2+ can obviously increase the activity and stability of
      this enzyme. Experiments show that the transformation efficiency of glutamate to
      glutamine is more than 95%. Because of the high cost from ATP, a system coupling
      GS with yeast for ATP regenaration was established. In this system, GS utilizes
      ATP released by yeast fermentation to synthesize L-glutamine. Yeast was treated
      by 2% toluence to increase its permeability and a yeast named YC001 with high
      yield of glutamine by coupling with recombinant GS was obtained. The good
      efficiency was achieved with the presence of 250 mmol/L glucose and 200 mmol/L
      phosphate, the transformation efficiency of glutamate to glutamine in this system
      is more than 80%, the average yield of glutamine is about 22g/L. This provides
      the basis for future large scale production of L-glutamine.

PMID- 15971625
TI  - [Cloning, expression of human keratinocyte growth factor and its purification and
      identification].
AB  - To clone KGF-2 gene, get hKGF-2 protein and detemine its activity. The cNDA of
      human KGF-2 was isolated from fetal lung by RT-PCR and cloned into pBV220
      plasmid. The recombinant pBV220-hKGF-2 plasmid was transformed into E. coli
      (BL21), induced at 42 degrees C for the expression of hKGF-2. Recombinant human
      KGF-2 was purified from the ultrasonic-treated BL21 by heparin-Sepharose CL-6B
      treated column chromatography and cation exchange column chromatography. MTT
      method was used for the determination of its biological activity. SDS-PAGE showed
      that rhKGF-2 was expressed in E. coli BL21 as soluble protein of approximately
      20kD. The rhKGF-2 protein can stimulate the proliferation of NIH3T3 cells
      significantly from 1 ng/mL to 10 ng/mL. HKGF-2 cDNA wasclned and highly expressed
      in E. coli BL21 and the purified rhKGF-2 showed the mitogenic activity on NIH3T3
      cells.

PMID- 15971626
TI  - Standards of occupational and environmental health nursing.

PMID- 15971627
TI  - Work related injury and illness.

PMID- 15971628
TI  - What are some of the challenges in case management and how have you handled them?
AB  - Case Management Update appears as part of Clinical Rounds in the Journal. The
      panel approach provides a forum for sharing ideas, viewpoints, and perspectives.
      Panel members come with expertise from a variety of case management arenas and
      have agreed to share their opinions and perspectives in response to specific
      questions or scenarios. Opinions and perspectives are those of the panel members,
      and do not necessarily represent the views of the AAOHN, the Editor, or the
      Publisher. We encourage readers to submit their questions or scenarios for the
      Panel. This month's Panel member is Robin Tourigian.

PMID- 15971629
TI  - What the research shows--worker exposures at a popcorn plant.

PMID- 15971630
TI  - Diagnosis: Chronic kidney disease, now what!
AB  - The occupational health nurse can play an important role in supporting employees
      with CKD and ESRD by recognizing risk factors such as diabetes and hypertension
      associated with CKD. The occupational health nurse should encourage compliance
      with treatment regimens that retard or delay progression of kidney disease into
      the next stage, especially blood pressure and glucose control. When employees are
      in need of diagnostic testing, the occupational health nurse can describe the
      testing procedures such as laboratory values, ultrasounds, and biopsies, and
      explain the five stages of CKD. The occupational health nurse can assist
      employees in Stage 4 or 5 CKD in deciding on a treatment option modality that
      best suits their individual lifestyles, after they have seen a nephrologist and
      kidney patient educator. In addition, the occupational health nurse can guide
      employees with difficult lifestyle changes and provide support during the
      adjustment process. The occupational health nurse also can play a key role in
      facilitating and coordinating those changes with the renal social worker.
      Together they can explore available resources, such as the NKF, the American
      Association of Kidney Patients, and kidneydirections.com. See the Sidebar on
      pages 295 to 296 for other available resources. Kidney disease can be a
      devastating diagnosis. Support and education are key to a successful lifestyle
      transition. Employees who have CKD and work with an occupational health nurse who
      is informed about their disease and its stages of progression can benefit from
      educational processes that create informed choices to delay or retard the
      progression of their renal disease.

PMID- 15971631
TI  - Integrating disability management into strategic plans: creating healthy
      organizations.
AB  - The integration of disability management into the strategic planning of a
      corporation ensures a work environment is created that motivates employees to
      consistently meet customer expectations. Disability management strategies can
      achieve significant decreases to the human and financial cost of workers'
      compensation, sick leave or short term disability, and long-term disability. The
      business case for disability management including effective return to work
      programs clearly supports program implementation to enhance employee engagement,
      delivery of corporate priorities, and improvement to the company's bottom line.

PMID- 15971632
TI  - Malaria: a parasitic disease.
AB  - Travelers and clinicians should be able to understand how malaria is transmitted,
      identify key risk factors associated with malaria, know how to prevent malaria,
      and recognize the symptoms associated with malaria. It is essential to provide
      accurate information about malaria, prevention, and treatment. All travelers
      should understand the importance of seeking immediate medical attention whenever
      they become ill. Development and implementation of a "train the trainer" program
      can help minimize the impact of malaria while providing accurate and up to date
      information.

PMID- 15971633
TI  - Focus on osteoporosis.

PMID- 15971635
TI  - [Acute schizophrenia concept and definition: investigation of a French
      psychiatrist population].
AB  - For schizophrenic disorders, the clinical conception of "acute state" is widely
      used in clinical settings to assess the effectiveness of therapeutic programs as
      well as epidemiological studies. Schizophrenic-specific symptomatology
      modification, need for hospitalization, significant change in care, disturbances
      in social behavior or suicide attempts were all used to define acute
      schizophrenic state. The decision to hospitalize is frequently used to define
      acute state but refers to multiple factors such as mood disorder, suicide
      attempts, drug abuse or social and environmental problems. Indeed, several and
      distinct definitions in a criteria basis form are available but no one has
      reached consensus. Because recognition of acute schizophrenic state remains based
      on the subjective clinician's advice, epidemiological and therapeutic studies
      fail in validity and reliability. The aim of the study was to evaluate how a
      population of French psychiatrists define criteria and therapeutic targets of
      acute schizophrenic state in their clinical practice. Psychiatrists filled out a
      self administered interview. At the time the interview was given, clinicians were
      notified that they were participating in a clinical consensus survey about
      schizophrenia. Six major indicators for acute state definition based on the
      literature data were proposed: general schizophrenic symptomatology modification
      (depression, anxiety, agitation, impulsivity/aggressiveness), specific
      schizophrenic symptomatology modification (positive symptoms, negative symptoms,
      disorganization), need for hospitalization, significant change in care,
      disturbance in social behavior and lastly, suicidal behavior. Minimal duration
      (1.2 or 4 weeks) of general and specific schizophrenic symptomatology
      modification required to define acute state were evaluated. The booklet included
      the 30 PANSS symptoms listed with their definitions. Among this symptom list,
      clinicians were instructed to select the ten criteria which they estimated best
      defined the acute state, followed by the ten most important target symptoms to be
      treated. Out of 2,369 questionnaires, 1,584 were collected on time (66.9%). Among
      the six majors indicators proposed to define acute state 75% of psychiatrists
      considered 1 to 3 criteria. Three were more frequently rated, including core
      schizophrenic symptomatology disturbance (68.4%), general schizophrenic
      symptomatology disturbance (68.0%) and suicidal behavior (64.9%). The other
      criteria were rated as follows: need for hospitalization (26.8%), significant
      change in care (18.3%), and disturbance in social behavior (29.1%). For 53.2% of
      psychiatrists the definition of acute state requires the presence of specific
      schizophrenic symptomatology for a minimal duration of one week. Two weeks with
      general symptomatology was required for 45.5% of psychiatrists to define acute
      state. Symptoms more often rated within the four first choices for acute state
      definition included delusions, conceptual disorganization, hallucinatory behavior
      and excitement. Except for grandiosity, all the PANSS positive subscale items
      were chosen to be included in the definition (delusions, conceptual
      disorganization, hallucinatory behavior, excitement, suspiciousness/persecution
      and hostility). Four items, including anxiety, depression, uncontrolled
      hostility, inner tension from the general psychopathology subscale were chosen as
      part of the ten most important criteria to define acute state. On the PANSS
      negative subscale (blunted affect, emotional withdrawal, poor relationships,
      passive apathetic withdrawal, difficulty in abstract thinking, lack of
      spontaneity/flow of conversation and stereotyped thinking), no item was rated to
      be included in the acute state definition. The highest rated symptoms among the
      four first choices for treatment included delusions, hallucinatory behavior,
      excitement and anxiety. The ten most important criteria for treatment were the
      same as for acute state definition with differences in frequency. Excited state,
      depression and suspiciousness/persecution were more rated for treatment than
      definition whereas delusion, hostility and conceptual disorganization were less
      rated as treatment target than definition criteria. In clinical practice,
      recognition of acute schizophrenic state is underscored by the association of
      specific schizophrenic symptomatology (positive symptoms, negative symptoms,
      disorganization) and general symptomatology (impulsivity/aggressiveness, anxiety,
      depression, agitation) of schizophrenia. For most clinicians, acute state
      definition requires specific symptom for a minimum of one week and other non
      specific indicators such as suicidal behaviour have to be taken into account.
      With regard to PANSS criteria, most positive schizophrenic symptoms and some
      general schizophrenic symptoms are necessary for definition and designated as
      treatment priorities. Negative symptoms were not taken into account.
      Hallucinatory behavior is the first symptom rated in definition and is considered
      by psychiatrists as the absolute therapeutic priority. This survey could be a
      first step in the construction of an operational and consensual definition. This
      definition is strongly needed as a valid measurement in therapeutic and
      epidemiological outcome studies, which remain at least partly based on clinician
      subjective judgment.

PMID- 15971636
TI  - [Assessment of metabolic impairments inducted by atypical antipsychotics among
      schizophrenic patients].
AB  - Conventional and atypical antipsychotics are known to induce weight gain, cause
      glucose and lipid impairments among schizophrenic patients. These impairments
      contribute to the intrinsic risk factors linked to the psychiatric pathology
      (sedentary state, nicotin addiction, diabetes) increasing numbers of
      cardiovascular complications. We propose to study ponderal modifications and
      presence of metabolic abnormalities in a population of schizophrenic patients
      treated by conventional or atypical antipsychotics, depending on the received
      treatment; 32 patients, whose schizophrenia diagnosis had been previously made,
      were consecutively included over a 4 months period. They were divided into three
      groups: patients treated by conventional antipsychotics (n = 6), by atypical
      antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%)
      display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4
      other patients (12.5%) have hypercholesterolemia. No particular drug could be
      directly targeted, partly because of the restricted size of our sample, but the
      patients presenting metabolism impairment were treated by atypical antipsychotic.
      The observance of these abnormalities is reflected in publications and lead to
      some antipsychotic treatments monitoring rules.

PMID- 15971637
TI  - [Personality tests and gender identification in male transsexuals].
AB  - The aim of this research project was to study gender identification in male
      transsexuals compared to male and female controls, using the Rorschach test and
      the MMPI. In the international literature, many researches have shown that the
      nature of the human response on Rorschach card III is linked to gender
      identification, as is the MMPI Mf scale. Ten untreated male homosexual
      transsexuals and 18 treated and operated male homosexual transsexuals were
      compared to 10 male and 12 female controls regarding verbal IQ, human content on
      Rorschach card III and the MMPI Mf scale. Absence of hormonal treatment for the
      first group of transsexuals was checked by a blood test at the time of the
      psychological testing. Responses on Rorschach card III were scored according to
      different kinds of human contents: male (M), female (F), gender
      unidentified/neutral (N), bisexual (B), feminine then masculine or the opposite
      (M/F), and nonhuman (NH). N, B, M/F and NH responses were rare in all Rorschach
      protocols. As expected, responses given by participants in the control group were
      significantly more consistent with their anatomical sex than with the opposite
      sex. Untreated transsexuals do not differ from treated and operated transsexuals
      on Rorschach data, and both transsexual groups give significantly more female
      human representations than male controls. Transsexuals' results are similar to
      female controls. Untreated transsexuals' mean score on the MMPI Mf scale is
      significantly higher than that of treated and operated transsexuals' score, in
      the male profile (biological sex). Both groups of transsexuals score higher on
      the Mf scale in the male profile than in the female profile. The mean Mf score in
      the male profile is significantly higher than that of male controls, whereas, in
      the female profile, the mean Mf score is similar to that of female controls. This
      study shows that for both groups of transsexuals, results are homogenous in
      respect of Rorschach and MMPI, showing hyper-conformism to self-perceived gender.
      Results in both groups are similar to results of female controls, but tend to
      show even more feminine gender identification. The absence of any significant
      difference between untreated and treated and operated transsexuals seems
      surprising, suggesting that the hormonal treatment has not had a major impact on
      gender identification processes. It would doubtless be interesting to study
      gender identification using even more kinds of data: all human contents in the
      Rorschach protocol (not just the responses given to card III), MMPI Mf scale,
      Draw-A-Person Test and Animal-and-Opposite Drawing Test. This would enhance
      result liability and could provide useful information about how gendter
      identification processes evolve after surgical sex reassigment.

PMID- 15971638
TI  - [The estimation of premorbid intelligence levels in French speakers].
AB  - Knowledge of cognitive performance earlier in life is essential in order to
      characterize precisely the extent to which these abilities have declined when an
      individual is diagnosed as having a dementing illness. The National Adult Reading
      Test (NART) was developed by Nelson and O'Connell to estimate premorbid
      intellectual ability in patients suffering from intellectual deterioration due to
      dementia. The test consists of 50 words, graded in difficulty, whose
      pronunciation cannot be determined from their spelling. The ability to
      successfully read irregularly spelt words is relatively robust in the face of
      current cognitive impairment and is a sensitive marker of intellectual
      attainment. Because the NART relies on orthographic irregularities in the English
      language, the construction of analogues of the test in other languages is not
      simply a matter of translation of the test content. Rather, words in the target
      language that have comparable properties to those in the NART must be sought. A
      French adaptation of the NART--the fNART--was developed by Bovet and calibrated
      on a small French-speaking Swiss sample. In a sample of 30 nondemented subjects,
      number of words pronounced correctly correlated highly with WAIS-R verbal and
      total IQ scores and less strongly with performance IQ (r = 0.43). Data available
      from an epidemiological survey undertaken in Geneva, Switzerland provided an
      opportunity to establish the measurement properties and construct validity of the
      fNART in a large sample unselected with respect to cognitive decline. In addition
      to the fNART, the survey incorporated a brief test battery assessing the domains
      of crystallized intelligence, memory and cognitive speed. An interview that
      enabled the diagnosis of dementia according to DSM IV criteria, the Mini Mental
      State Examination and the Psychogeriatric Assessment Scales (PAS) were also
      administered. If the fNART measures intellectual ability, substantial
      correlations between it and the test battery would be expected. Further
      validation of the test was sought by exploring its relation with years of
      education. The stability of the fNART was assessed by comparing the scores of
      subjects with and without dementia, and by examining the relationship of fNART
      scores to an informant-based report of change in cognitive performance from
      earlier in life assessed in the PAS. If the fNART is stable in the face of
      cognitive deterioration, no between-group differences or association with
      reported cognitive change would be expected. METHOD: Subjects were randomly
      selected from residents of the canton of Geneva aged over 65 years. The analyses
      reported here were undertaken on a sample of 368 persons who gave codable
      responses to at least 90% of the fNART items. They ranged in age from 65 to 94
      years. Subjects were interviewed in their homes by trained lay interviewers.
      RESULTS: Cronbach's alpha for the forty-item scale was high (0.89). The
      percentage of subjects correctly pronouncing words ranged from 7.3% for "chamsin"
      to 96.7% for "agenda". Item response theory (IRT) models were fitted to the data.
      In a three-parameter model the value of the guessing (asymptote) parameter was
      vanishing small for all items. Accordingly, a two-parameter model was adopted.
      The discriminating power (slope) of items ranged considerably from 0.281 (rebus)
      to 1.192 (beotien). The average slope was 0.656. This corresponds to average
      factor loading of 0.528 (range 0.270 to 0.766.) The items measure a broad range
      of ability (mean threshold--0.719, sd = 1.540). Most items, however, discriminate
      at moderate levels. The parameter values obtained in the current study were
      compared to those estimated in a French sample of persons at risk of dementia .
      The correlation between item pairs for slope and parameter estimates was 0.53 and
      0.70 respectively. This indicated substantial concordance between the samples
      regarding the difficulty of the items, but some differences in the power of
      groups to differentiate ability. In particular, a small number of words that
      performed very well in the "at risk" sample showed more moderate discrimination
      in the current study. Scores on the fNART were correlated with measures of
      crystallised intelligence, memory and cognitive speed. All correlations were
      statistically significant. With all tests entered a regression equation the
      multiple correlation coefficient was 0.63. Mean fNART scores of those suffering
      from DSM IV dementia and those meeting only Criterion A (multiple cognitive
      deficits) were lower than those of subjects meeting neither set of criteria.
      However subjects in the first two groups were older than subjects in the
      undemented group and had significantly lower educational attainment. When these
      two factors were controlled in an analysis of covariance, the magnitude of the
      differences between the groups, while still overall significantly different, was
      substantially reduced. A similar pattern of results applied when psychometric
      measures of cognitive state--the MMSE and the PAS Cognitive Impairment Scale-
      were used instead of diagnostic categories. The partial correlations of the fNART
      with the MMSE and PAS cognitive impairment scale controlling for age and
      education were 0.25 (P < 0.01) and -0.33 (P < 0.01) respectively. fNART scores
      did not differ between the sexes, nor were they significantly correlated with PAS
      Depression, Stroke or Behaviour Change scales. There was a small but significant
      correlation between the fNART and informant-assessed Cognitive Decline on the
      PAS. DISCUSSION: This study demonstrated the excellent measurement properties of
      a French adaptation of the National Adult Reading Test in a large probability
      sample of elderly native speakers and provided the first large-sample evidence to
      support the validity of the fNART as a test of intellectual functioning
      relatively robust to dementia status. The negligible values of the pseudo
      guessing parameters suggest that the goal of choosing words whose pronunciation
      is not susceptible to guessing has been achieved. The average item
      discriminability was high and the words used covered the spectrum of ability. The
      finding of substantial relationships of cognitive performance and educational
      attainment with fNART scores is important in validating the test as a measure of
      premorbid cognitive ability. The low correlations of the fNART with informant
      based assessment of cognitive decline and age support the fNART as being relative
      robust to decline in ability. The relationships observed in this French
      adaptation are comparable to those reported for the English instrument . However,
      subjects meeting DSM IV criteria for dementia or Criterion A only had lower
      scores than other subjects. Decline in NART scores with dementia has been
      observed, particularly in moderate and severe cases. Given that the mechanism of
      the fNART is the same as the NART it is to be expected that while generally
      robust to current dementia status, some decline in performance will occur with
      the progression of the disease. The relationships between the fNART and PAS
      scales was remarkably similar to those reported by Jorm et al. in an English
      speaking sample between the PAS and NART. Although small, the correlation between
      the fNART and the PAS Cognitive Decline scale might have been expected to be non
      significant if the measure were truly stable in the face of intellectual
      deterioration. However this correlation is mirrored in the original English
      instruments and may reflect the higher risk of dementia in persons of lower
      intellectual ability. CONCLUSION: Further research is desirable to improve the
      precision of the calibration of the scale against the WAIS-R. Nevertheless, this
      study has demonstrated that the fNART is a reliable and valid method of assessing
      premorbid intellectual ability in French speakers.

PMID- 15971639
TI  - [Comorbidity between eating disorders and anxiety disorders. First part:
      methodological review].
AB  - The objective of our work is to conduct a critical literature review on studies
      assessing the prevalence of anxiety disorders (AD) in subjects with eating
      disorders (ED) (anorexia nervosa and bulimia nervosa). In the first part (this
      paper), we will discuss methodological issues relevant to comorbidity studies
      between ED and AD. METHOD: We performed a manual and computerised search
      (Medline) for all published studies on comorbidity between ED and AD, limiting
      our search to the 1985-2002 period, in order to get sufficiently homogeneous
      diagnostic criteria for both categories of disorders (most often RDC, DSM III,
      DSM Ill-R, or DSM IV criteria). RESULTS: We review methodological issues
      regarding population sources, general methodological procedures, diagnostic
      criteria for ED and AD, diagnostic instruments, age of subjects and course of the
      eating disorder. DISCUSSION: We give implications for reviewing the results of
      published studies and planing future research.

PMID- 15971640
TI  - [Morningness-Eveningness for Children Scale: psychometric properties and month of
      birth effect].
AB  - There is strong evidence that individuals can be arranged on a continuum from
      Eveningness to Morningness reflecting their preferred time range for different
      activities. This preference, which mostly reflects the phase of the circadian
      pacemaker, is determined in part by mutations on the CLOCK gene, and by
      environmental factors such as the month of birth. It has been suggested that
      eveningness might be a susceptibility factor for depressive disorders. Two self
      rated questionnaires are available (the Morningness-Eveningness Questionnaire,
      MEQ, and the Composite Scale for Morningness) and have been adapted for use with
      youngsters: the Junior-MEQ and the Morningness-Eveningness Scale for Children
      (MESC), respectively. Most studies concern adult samples, but it is accepted that
      puberty is associated with a phase delay in the circadian pacemaker die a shift
      towards eveningness) occuring around age 12 in both genders. In this study, we
      examined the psychometric properties of the French version of the MESC in 3
      independent samples of adolescents (total n = 392) recruited in the community or
      during hospitalization in paediatric department, most of them after they
      attempted suicide. A three-way ANCOVA showed no gender or age effect but rather a
      strong group effect: hospitalized adolescents scored about 3 points below the
      community samples (ie towards an eveningness tendency). In each sample, the
      internal consistency for this 10-item measure was satisfactory (mean alpha =
      0.76) and the same two-factor structure was found (Morningness and Planification)
      as shown by procrustes rotations. As expected, there was a negative correlation
      between the MESC scores and reported times of rising, of going to bed, of best
      intellectual and physical performances, but no correlation with the number of
      minutes of sleep needed. The test-retest stability was acceptable within a 8
      month delay although the sample size was limited (n = 20). In line with
      literature data, we found a modest negative correlation about -0.20 in 2 of the
      samples with two depression measures (MADRS and CES-D). Finally, we assessed the
      effect of the month of birth on the MESC total score by a non-linear regression
      adjusted for age and gender that included a one-cycle cosinus function. We found
      that birth in March-April was associated with eveningness while birth in
      September-October was associated with morningness. The peak and nadir occur two
      months before those found in a large sample of young adults. However, this result
      could not be replicated in the sample of hospitalized adolescents suggesting that
      the effect might have been smoothed by a "pathological" factor. Reasons for this
      descrepancy and implications for developmental psychiatry are discussed. More
      precisely, we postulate a relationship between morningness and impulsivity
      related personality traits. In conclusion, the MESC is a psychometrically sound
      instrument in need of further validity assessment.

PMID- 15971641
TI  - [Repeat suicide attempts: characteristics of repeaters versus first-time
      attempters admitted in the emergency of a Tunisian general hospital].
AB  - Repeat suicide attempts constitute a special problem in suicidology. It seems
      that the excess mortality by suicide is even higher among the suicide repeaters.
      The objectives of this study were to estimate repeat suicide attempts frequency
      among a sample of suicide attempters admitted in the University Hospital
      Emergency of Monastir (Tunisia), to compare their features to those of first-time
      attempters and to determine factors associated with repeat suicide. METHOD: A
      transversal survey involves a review of all patients committing suicide attempt
      and who are admitted in the emergency service during the second semester of 1999.
      Study variables included: demographic parameters, family and personal psychiatric
      history, axis I psychiatric disorder and circumstances of the present suicide
      attempt. Also, subjects were evaluated with the following scales: Montgomery and
      Asberg Depression Rating Scale (MADRS) and The Social Readjustment Rating Scale
      of Holms and Rahe. RESULT: Among the 90 suicide attempters, 42.2% (n = 38) had
      made at least one previous suicide attempt. More repeaters than first-time
      attempters were divorced or separated: 21.1% versus 5.8% (p = 0.05). Belonging to
      a numerous family (n > or = 4) was more frequent in the repeaters group: 73.7%
      versus 46.2% (p = 0.01). The two groups did not differ as to level of education
      but were significantly different with regard to their professional activity:
      60.5% of repeaters were unemployed versus 34.6% of first-time attempters (p =
      0.01). Repeaters had more loaded family psychiatric disorders: 26.3% versus 7.7%
      (p = 0.03). However there were practically no differences between repeaters and
      first-time attempters in regard of suicide in their families. Personal previous
      history of repeaters was characterized by frequency of psychiatric
      hospitalization: 50% versus 11.5% (p = 0.00005). Sexual abuse was more frequent
      in repeaters group but this difference was not significant. Alcohol and drug
      abuse were not frequent in the two groups. Concerning the actual suicide attempt,
      the most frequently diagnosed disorder was adjustment disorders. However
      depressive and psychotic disorders were significantly more frequent in the
      repeaters group: 34.2% versus 13.4% (p = 0.05). Repeaters had more frequently
      elevated scores (> 14) in MADRS: 71.1% versus 48.1% (p = 0.01), and raised
      intensity of stress factors lived during the six months preceding actual suicide
      attempt: 68.4% versus 42.3% (p = 0.04). Nevertheless we hadn't noticed any
      differences between the two groups regarding the methods used or the motives.
      CONCLUSION: Differences in the characteristics of repeaters and first-time
      attempters are therefore of interest when discussing future suicidal risk and
      should clear on preventive actions in order to face the increase of suicidal
      recidivism. A broad based, multidisciplinary intervention approach is
      recommended.

PMID- 15971642
TI  - [Alpha-thalassemias and bipolar disorders: a genetic link?].
AB  - After a previous paper discussing the possible association between beta
      thalassemias and bipolar disorder, this article considers a possible association
      between alpha-thalassemia and the bipolar disorder. We report the case of a 36
      year old woman with bipolar disorder and alpha-thalassemia. The patient, native
      of Reunion Island, has a family history of bipolar disorder (both parents, one
      brother, and a paternal uncle). The severity of the bipolar disorder type I in
      her family, is illustrated by the suicides of both parents, one brother and the
      paternal uncle, in intervals of only a few years. After a Medline review (1980
      2004) we found only two studies suggesting a possible relationship between
      bipolar disorders and alpha-thalassemias, but without clinical case report
      information. Some genetic studies described the existence of possible genetic
      susceptibility for bipolar disorder on the short arm of chromosome 16, close to
      the gene involved in certain alpha-thalassemias, on the region 16p13.3. An
      interesting finding is that the sequencing of 258 kb of the chromosome region
      16p13.3 not only allowed the identification of genes involved in the alpha
      thalassemia and in the vulnerability to bipolar disorders, but also the
      identification of genes implicated in tuberous sclerosis, in polycystic kidney
      disease, in cataract with microophtalmia, and in vulnerability genetic factors
      for ATR-16 syndrome, asthma, epilepsy, certain forms of autism and mental
      retardation. Numerous clinical descriptions and some familial studies on linkage
      suggested a possible relationship between tuberous sclerosis, polycystic kidney
      disease, cataract with microophtalmia, ATR-16 syndrome, asthma, epilepsy, certain
      forms of autism, mental retardation and bipolar disorder, given the closeness of
      these vulnerability genes on the short arm of the chromosome 16. A vulnerability
      gene of alcohol dependence was also identified on this same chromosome region
      (16p13.3), by a study concerning 105 families. Taking into account the
      methodological difficulties due to the clinical and genetic heterogeneity of
      bipolar disorder, we suggest that linkage techniques should be used to confirm
      the presence of susceptibility genetic factor for bipolar disorders on chromosome
      16. Thus a known genetic disease (alpha-thalassemia) could contribute to
      confirming the presence on the short arm of chromosome 16 of a susceptibility
      genetic factor for bipolar disorders. Linkage studies should be performed in
      families with a strong association for both diseases. Thanks to linkage
      techniques, one could hope for an improvement in understanding the
      physiopathology of bipolar disorder, with possible implications at a therapeutic
      level.

PMID- 15971643
TI  - [Post-traumatic stress disorder in an anxiety disorder unit and in a victims
      support association].
AB  - The post-traumatic stress disorder (PTSD) represents an original and frequent
      pathological entity concerning people confronted with one or more significant
      traumatic events. We present here a comparative study concerning subjects who
      present a post-traumatic stress disorder received in an anxiety disorder unit
      (ADU) or in a victims support association (VSA). One hundred and twenty seven
      people have been included in the study, according to DSMIV for PTSD, during three
      years. Fifty-seven came from a victim support association, 54 came from an
      anxiety disorder unit and 16 were common to both structures. The PCL-S (PTSD
      Checklist Scale) was used to rate the intensity of the PTSD. Age, sex, marital
      statute, type of traumatism, comorbidity and previous traumatisms were compared.
      PCLS scores were equivalent in the two settings. More women, younger subjects and
      more aggression were received in the victim support association. In the anxiety
      disorder unit more psychiatric comorbidity and more frequent antecedents of
      traumatism were seen. In the whole sample, two thirds of the people lived alone.
      Our results show that a victim support association receives people suffering from
      a definite post-traumatic stress disorder as intense on the PCL-S as in an
      anxiety disorder unit. More work has to be done on support association in the
      community, as they are confronted with significant PTSD problems.

PMID- 15971644
TI  - [Study of the categorization process among patients with eating disorders: a new
      cognitive approach to psychopathology].
AB  - Anorexic and bulimic patients have a highly distorted relationship with food and
      eating, even though they tend to be knowledgeable about diet and nutrition. The
      progress of this disease, as well as its complications and associated
      difficulties, are increasingly understood, while the etiopathogeny of eating
      disorders remains obscure. The approach that we are proposing involves the study
      of one of the most fundamental cognitive functions of human reasoning--the
      cognitive process of categorization. The purpose of this study is to understand
      the procedures used by these patients to construct representations of food.
      Categorization, one of the basic features of human cognition, allows individuals
      to organize their subjective experience of the surrounding environment by
      structuring its contents. This ability to group different objects into the same
      category based on their common characteristics is important for explaining the
      major cognitive activities of planning, memorization, communication and
      perception. Indeed, our categories reflect our conceptions of the world. They
      depend on our experiences and representations, as well as the expertise acquired
      in a specific field. The differences that appear in the categories created by
      subjects when they are asked to classify objects reveal the properties that are
      most salient to them and, as a result, the interests, values and ideas associated
      with these properties. There are three types of properties: perceptive
      properties, which describe the object's shape, color, odor and texture;
      structural properties, which relate to the object's components; and functional
      properties, which specify the way in which the object is used and provide an
      answer to the question, "What is it used for?". Subjects attribute these
      functional properties by means of knowledge or inference according to their
      representation of the object's role; such properties are especially likely to
      emerge during top-down (theory-driven) processing. The type of processing used
      (bottom-up or top-down) is dependent on a certain number of factors. We
      hypothesize, within the context of food product categorization, that patients
      suffering from eating disorders largely resort to processing based on acquired
      information or beliefs about the objects, i.e. top-down processing. We present
      two studies: a naturalistic and exploratory pilot study whose goal is to identify
      whether the various categorization processes used by eating disorder patients
      differ from those employed by subjects not suffering from an eating disorder. A
      second study aims to identify the different categorization procedures. During the
      first experiment, 68 women (17 control subjects, 17 anorexics, 17 anorexic
      bulimics and 17 bulimics) aged 18-39 (average age: 26.6) verbalize all
      representations that come to mind during a limited time period as the name of a
      food item is read. Eighty-nine food items are presented in alphabetical order.
      The list is read out loud and all comments are recorded. The data is processed in
      three ways : an analysis based on the positive or negative valence of each
      representation, an analysis based on each categories of food and an analysis of
      representations based on themes expressed. The three analyses (valence,
      categories of food and theme assigned to the representations) show differences
      between the representations of the four experimental groups. In fact, the
      anorexics and anorexic bulimics mainly express strongly negative representations
      about food, whereas bulimics and control produce representations whose positive
      and negative valences balances. These negative cognitions concern mainly meat for
      the control subjects and cakes for the subjects reached of TCA. Concerning theme
      assigned to the representations, the control subjects produce mainly cognitions
      relating to the hedonism, the flavor of food and their purpose on health. The
      anorexics and anorexics-bulimics evoke mainly the fat and sugar content of the
      foods. The bulimics evoke mainly cognitions relating to the effect on health and
      the intestinal transit time of food. These results lead one to believe that it is
      not the bulimic binging and purging of these patients, but rather their
      restrictive behavior that is the determining factor in the differences in food
      representations observed between the two experimental groups. During the second
      experiment, 60 women (15 controls, 15 anorexics, 15 anorexic bulimics and 15
      bulimics) aged 18-32 (average age: 25.6) classified 27 food names according to
      their similarities and differences, and then explained the reasons for their
      categorizations. The data were analyzed in terms of similarity/difference, and
      the verbalizations were analyzed by content. The results indicate that 10 of the
      27 foods were categorized differently by the controls and the subjects with
      eating disorders. Subjects classified the following foods: camembert cheese, cold
      cuts, cheese spread, fruit in syrup, whole milk, mayonnaise, bread, fresh fish,
      potatoes and plain yogurt. Bulimics and controls use similar classifications for
      food names, while anorexics and atypical bulimics classify foods in a similar
      way. Examining the categorization criteria used during verbalizations allows us
      to better understand these differences. The control group's major criterion seems
      to be the succession of dishes. These subjects group into separate categories
      entry foods (beef, eggs, fish, etc.), vegetables, cheese or dairy foods, and
      finally desserts. Additional foods, like bread and mayonnaise, belong to the same
      category. Other categories are nutritional criteria (for example, dairy products
      contain calcium) and biological criteria (for example, bananas and apples are
      fruits). These categorization criteria include structural properties (which
      describe what the object is made of) and functional, "academic" properties, those
      which describe how foods are used, "as in cookbooks or diet books." On the other
      hand, the categorization criteria expressed by anorexic patients are very
      different from those used by control subjects: foods that are hard to eliminate,
      rich, high-fat and therefore indigestible are considered to be similar. Some
      examples are cold cuts, potatoes, mayonnaise and prepared desserts. A second
      categorization criterion involves the concept of natural foods : certain foods
      "are unhealthy because they're processed, so they're bad for you"--one such
      example is cheese spread. A third criterion concerns the notion of familiar
      foods: poultry and eggs, for example, are "familiar to us." We are clearly seeing
      here the importance of functional properties in the categorization of food names:
      certain foods are indigestible, hard to eliminate, cause heartburn or reflux, are
      not natural, and thus are avoided. The categorization criteria mentioned by
      bulimic patients also clearly take into account the functional properties of
      foods. The criteria are of the following type: "it's filling, it relieves a
      bulimic attack, it helps prevent heartburn and constipation, etc." It appears
      that bulimics' categorization criteria are solely associated with these foods'
      imagined or real effect on the body. The categorization criteria used by anorexic
      bulimics seem to be especially associated with weight gain or the consumption of
      such foods during bulimia attacks because "they make you feel full." On the other
      hand, light foods, which patients allow themselves to eat, are placed in the same
      category. This study, which seeks to understand the cognitive functioning of
      eating disorder patients with anorexia and bulimia, has brought new elements to
      light. All patients exhibit food categorization processes that differ greatly
      from those displayed by control subjects. Patients also attribute greater
      significance to the functional properties of foods as compared to controls, who
      give priority to structural properties. Anorexic and bulimic patients base their
      food categorizations on the consequences of ingestion, in terms of health,
      digestion and weight gain. Their processing of food stimuli is therefore
      radically different and gives a dominating place to top-down processes.
      Additional studies should supplement these findings in order to gain a better
      understanding of patients' disturbed processing of information.

PMID- 15971645
TI  - [Guidelines for substitution treatments in prison populations].
AB  - Care access for the drug addict patients in prison (in particular for the
      treatments of substitution) in France is very unequal from one establishment to
      another. This reflects the great variability of the practices of substitution and
      especially the absence of consensus on the methods of adaptation of these
      practices to the prison environment. Because of difficulties expressed by
      prisoners and medical staff on this subject and of stakes (let us recall that
      approximately 30% of the prisoners are dependent or abusers of one or more
      psychoactive substances), the formulation of recommendations or of a good
      practices guide of substitution in prison appeared necessary. Work that we detail
      here answers a ordering of the Advisory Commission of the Treatments of
      Substitution (September 2001) whose authors are members. It was presented at the
      session April 2003. It results from the confrontation of a review of the
      literature (including legal texts and official reports concerning substitution,
      the organization of the care in prison environment and the lawful framework),
      with a vast investigation. The latter was carried out near medical staff (22
      prisons), penitentiary staff (3 prisons, 27 people met including directors of
      these establishments) and prisoners (7 establishments, 28 prisoners met) in the
      form of individual talks (semi-directing interviews with evaluation of the type
      of existing device and its knowledge by the penitentiary staff and the prisoners;
      statement of the suggestions, needs and requests of the medical, penitentiary
      staffs and of the prisoners). In the whole visited prisons, 7.8% (870) of the
      prisoners received substitution treatments (6.35% by buprenorphine, 1.44% by
      methadone), representing a proportion of substituted drug addicts (870
      substituted for an evaluation of 3,350 prisoners drug addicts among the 11,168
      prisoners of the 22 visited prisons) notably lower than that in free environment
      (56%, ie 96,000 substituted for an evaluated population of drug addicts for
      heroin of 160,000). There are however considerable variations (from 0 to 16.2%)
      of the proportion of substituted of one establishment for the other according to
      the type of prison, of its size, its localization and the type of medical device
      present. If a consensus exists for methadone (daily delivery with sanitary
      control), the organization of the care relating to the buprenorphine is extremely
      variable from one establishment to another, often putting in difficulty as well
      the medical teams as the prisoners. One recommendation is essential: the
      formulation of an individualized therapeutic project. Thirteen other
      recommendations are made in the following fields: renewal of substitution
      treatments, initiation of substitution treatments, urinary controls, methods of
      prescription, methods of delivery, co-prescriptions, global care,
      confidentiality, files, exits and transfers, extractions, formation,
      accompaniment of the teams. These recommendations being formulated, many medical
      concerns remain present and several questions open. The report of joint mission
      IGAS/IGSJ of June 2001 on the health of the prisoners underlines the principal
      persistent gaps: hygiene and public health, treatment of the mental disorders,
      the follow-up of the sexual delinquents, handling ageing, handicap and the end of
      lifetime. In the same way, the difficulties listed in prison environment
      concerning substitution are only the exacerbation of those existing outside: the
      misuses and traffics are common in free environment, risk reduction in prison, as
      outside, handle with obstacles related to the penalization of the drug use and
      can hardly evolve except questioning the law of 1970. The prison practice opens
      also questions: that of the "duration" of the substitution, frequently posed by
      the prisoners; concern to see the prison becoming a privileged place of access to
      the care, combining sanction and care whereas the law of 1970 allows the
      alternative (care or sanction); that of the clinic of the misuse, particularly
      "readable" in prison environment; and finally the question of the shared secrecy,
      extremely delicate in prison context although clarified by the law of March 04,
      2002.

PMID- 15971646
TI  - [A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced
      by divalproate sodium prescribed for bipolar disorder].
AB  - Several cases of Parkinsonian syndrome, cognitive impairment or hyperammonemia
      induced by sodium valproate have been described in the literature. We report the
      first case presenting an association of the three adverse effects occurring with
      divalproate sodium prescribed for bipolar disorder: a 58-year-old man with a
      history of bipolar type I disorder presented with Parkinsonian syndrome and
      cognitive impairment of insidious onset. This patient had been treated for
      several years with lithium carbonate, with a successful effect on mood swings,
      but with distressing adverse effects such as hand tremor and diarrhoea. Lithium
      therapy was progressively withdrawn while sodium divalproate was initiated.
      Associated medications, unchanged for several years, were amisulpride (daily
      dose: 100 mg), liothyronine, ciprofibrate and benfluorex. The patient was treated
      with sodium divalproate for seven months (daily dose: 1,000 mg), and with
      trihexyphenidyle for one month for extrapyramidal symptoms. At hospital
      admission, he presented with temporal disorientation, slowed thinking, severe
      anterograde memory deficits, and Parkinsonian syndrome. The minimal mental state
      (MMS) score was 16 (maximum: 30). The patient was anxious but did no present with
      mood symptoms. He also developed hyperammonemia (124 micromol/liter, normal
      range: 15 to 60 micromol/liter) without signs or biochemical evidence of hepatic
      failure. Valproate concentrations were within the therapeutic ranges (79 mg/l,
      normal range: 50 to 100 mg/l). The CT-scan showed cerebral and cerebellar atrophy
      with enlarged ventricles. The electroencephalogram showed generalized slowing
      waves. All the symptoms resolved within one month after the withdrawal of
      divalproate: the extrapyramidal hypertonia resolved, the MMS score was 29. The CT
      scan and the electroencephalogram returned to normal. The divalproate was
      replaced by lithium. After a one-year follow-up, the cognitive and neurological
      symptomatology did not reappear at the exception of the pre-existing hand tremor.
      The pathophysiology of valproate induced hyperammonemic encephalopathy remains
      unclear. A possible mechanism is neuronal toxicity induced by increased
      intracellular concentrations of glutamate and ammonium in astrocytes. Indeed,
      these abnormal intracellular concentrations increase the intracellular osmolarity
      and thus induce rise in intracranial pressure and cerebral oedema. Reversible
      dementia could be due to a direct toxic effect of valproate on the central
      nervous system or to an indirect effect mediated through valproate-induced
      hyperammonemia. It has been suggested that the occurrence of extrapyramidal
      syndrome could be explained by a disturbance in the GABAergic pathways inducing
      reversible dopamine inhibition. A drug adverse reaction should always be
      considered when a patient treated with valproate presents with extrapyramidal
      symptoms and cognitive disorders even when valproate concentrations are within
      standard therapeutic ranges.

PMID- 15971647
TI  - Prognostic implications of site of recurrence in patients with recurrent well
      differentiated thyroid cancer.
AB  - OBJECTIVE: The site of treatment failure in patients with recurrent well
      differentiated thyroid carcinoma (WDTC) has implications for both the mode of
      salvage therapy and disease-specific prognosis. The objective of this study was
      to evaluate the prognostic significance of the site of failure in patients with
      recurrent WDTC. DESIGN: Patients with recurrent thyroid cancer were identified
      retrospectively from 1963 to 2000. SETTING: Data were retrieved from the thyroid
      cancer database at the Department of Otolaryngology-Head and Neck Surgery, Mount
      Sinai Hospital, Toronto (1963-2000). METHODS: Patients were placed into four
      different groups according to their site of recurrence: group 1, local
      recurrence; group 2, regional recurrence; group 3, distant recurrence; and group
      4, unspecified recurrence. Patient, tumour, and treatment data were collected and
      compared. The Kaplan-Meier method was used to calculate survival data, and curves
      were compared using the log rank test. MAIN OUTCOME MEASURES: Outcome included
      alive, no disease; alive with disease; dead, no disease; and dead of disease.
      RESULTS: Seventy-three patients (21 male, 52 female; median age 44 years, range
      18-84 years) were eligible for inclusion in this study. Relevant data were
      divided according to group 1, 22 patients; group 2, 24 patients; group 3, 13
      patients; and group 4, 14 patients. The groups were comparable in terms of
      primary tumour and treatment factors. The actuarial disease-specific survival
      rate after salvage therapy was less significant in patients who developed a
      distant recurrence versus a local recurrence, a regional recurrence, or an
      unspecified recurrence (ie, 66% vs 95%, 88%, and 92%, respectively; p = .06).
      CONCLUSIONS: Patients with distant recurrences have a poor prognosis, with a
      significant reduction in the actuarial disease-specific survival rate.

PMID- 15971648
TI  - Evidence of allergic inflammation in the middle ear and nasopharynx in atopic
      children with otitis media with effusion.
AB  - BACKGROUND: Otitis media with effusion (OME) occurs in the setting of eustachian
      tube (ET) dysfunction. Previous studies have demonstrated a predominance of T
      helper 2 (Th2) mediators in the middle ear effusions (MEEs) of atopic children,
      suggesting that allergy plays a role in the pathogenesis of OME. Given that the
      middle ear is contiguous with the upper airway, the allergic inflammation seen in
      the middle ear of atopic patients with OME may also have been observed in the
      nasopharynx. OBJECTIVE: We hypothesize that atopic children have different
      cellular and cytokine profiles in MEE compared with nonatopic patients and that
      this allergic inflammation occurs in both the middle ear and the nasopharynx.
      METHODS: Forty-five patients undergoing both ventilation tube placement for OME
      and adenoidectomy for adenoid hypertrophy were recruited. The atopic status was
      determined for each patient using standard skin testing. The cellular and
      cytokine profiles of the MEEs and the torus tubarius and adenoid tissues were
      investigated using immunocytochemistry and in situ hybridization. RESULTS: Our
      results indicate that, within the atopic patient, there is a similar cellular and
      cytokine profile within the three regions sampled, with a predominant expression
      of interleukin-4 (a Th2 cytokine) and an increased infiltration of eosinophils
      compared with the nonatopic patient. CONCLUSION: These findings confirm the
      association of allergy with MEE and support the hypothesis that the middle ear
      may be an integral part of the United Airway Concept.

PMID- 15971649
TI  - Retropharyngeal abscess in children: 10-year study.
AB  - OBJECTIVE: Retrospective analysis of all patients treated for retropharyngeal
      infection in a tertiary care pediatric hospital. METHODS: Charts were reviewed
      for demographic data, duration of symptoms, radiologic workup, antibiotic choice,
      microbiologic findings, surgical approach, complications, and duration of medical
      therapy. Surgical findings were correlated with computed tomographic (CT) scans.
      RESULTS: Sixty-eight patients were included in the study. Empirical intravenous
      clindamycin was started for a trial of conservative medical therapy. Fifty-one
      patients (75%) responded to medical treatment, and only 17 patients (25%)
      required surgical intervention. The CT scan showed a sensitivity of 43% and a
      specificity of 63% in this series. None of the patients with retropharyngeal
      infection died, had a major complication, or had a recurrence. CONCLUSION: Based
      on the current study, we propose that all patients should be given a trial of
      medical treatment with intravenous clindamycin. Surgery should be reserved for
      those who do not respond. An extensive review of the literature is presented.

PMID- 15971650
TI  - Functional outcomes after hemiglossectomy and reconstruction with a bilobed
      radial forearm free flap.
AB  - OBJECTIVE: This study examines prospectively the functional outcomes of a cohort
      of patients who had undergone hemiglossectomy and reconstruction with a bilobed
      radial forearm free flap (RFFF) for oral tongue squamous cell carcinoma. METHODS:
      Speech and swallowing data were compiled for patients treated for oral tongue
      cancer with hemiglossectomy and and reconstruction with a bilobed RFFF. The three
      evaluation periods were preoperative, postoperatively, and postradiation therapy.
      RESULTS: Eleven patients were included in the study. A significant difference
      between preoperative and postoperative single-word intelligibility scores was
      observed. There was no significant difference across any of the evaluation times
      for sentence intelligibility. Swallowing analysis revealed fewer instances of
      laryngeal penetration with liquids postoperatively. No significant differences
      were found in laryngeal penetration with either the pudding or cookie
      consistencies across any of the evaluation times. There was no incidence of
      aspiration at any of the evaluation times. There were no significant differences
      in the number of problems with the oral or oral preparatory phases across any of
      the evaluation times. The neurotization status of the RFFF had no significant
      effect on any of the observed speech or swallowing parameters. CONCLUSIONS: The
      bilobed RFFF provides functional speech and excellent swallowing outcomes in the
      reconstruction of hemiglossectomy defects.

PMID- 15971651
TI  - Lateral neck radiography versus direct video rhinoscopy in assessing adenoid
      size.
AB  - OBJECTIVE: To evaluate the usefulness of adynamic lateral neck radiographs and
      dynamic video rhinoscopy in assessing adenoid size and the relationship of these
      methods to associated symptoms and thus the severity of the disease. METHODS:
      Children with suspected adenoid hypertrophy underwent standard lateral neck soft
      tissue radiographs: the percentage of airway occlusion, adenoid to nasopharynx
      (AN) ratio, airway to soft palate ratio, and adenoid thickness were assessed by a
      radiologist. The percentage of airway closure was assessed by direct fibre-optic
      rhinoscopy in an ear, nose, and throat clinic. Associated clinical symptoms were
      assessed by parents using a standardized questionnaire, evaluating the severity
      of symptoms (snoring, sleep apnea, mouth breathing, and otitis media) to give a
      total symptom score out of 16. RESULTS: Nonparametric statistical analysis using
      Spearman's correlation coefficients was performed on 32 patients. There was a
      weak correlation, which approaches significance, between the percentage of airway
      occlusion assessed by fibre-optic rhinoscopy and the total symptom score (r =
      .344, p = .054). However, this correlation becomes significant when the frequency
      of otitis media is omitted (r = .367, p = .039). There was also a significant
      correlation between airway occlusion assessed by rhinoscopy and the percentage of
      airway occlusion as determined by lateral neck radiography (r = .431, p = .014).
      There was no correlation between any of the measurements taken by lateral soft
      tissue neck radiography and total symptom score. CONCLUSION: Dynamic video
      rhinoscopy is more accurate at assessing adenoid hypertrophy, and the percentage
      of airway occlusion, as estimated by video rhinoscopy, is better correlated to
      the severity of symptoms than are values obtained by lateral neck radiography.

PMID- 15971652
TI  - Evaluating the reproducibility of sinus lavages with a saline solution
      administered directly in the maxillary sinus of patients after endoscopic sinus
      surgery.
AB  - INTRODUCTION: Chronic sinusitis is recognized as having a strong inflammatory
      component, and failures of endoscopic sinus surgery (ESS) are frequently
      attributed to persistent inflammation. A test that would allow rhinologists to
      evaluate the inflammatory state of a patient's sinuses would be helpful to
      evaluate cases refractory to therapy, determine appropriate medical therapy, and
      monitor the response to therapy. OBJECTIVES: The goal of this preliminary
      research is to assess the optimal method of collection and the reproducibility
      and specificity of sinus lavages. METHOD: Twelve patients who had undergone ESS
      were recruited. They were divided into two groups according to the persistence of
      their symptoms and the recurrence of acute sinusitis after ESS. The subjects were
      seen twice. Three successive lavages were collected from each maxillary sinus and
      were analyzed by cell count. RESULTS: Intrasession cell counts were most
      reproducible (Spearman rank correlation .7 for eosinophils and .6 for
      neutrophils) for the second lavage. Intersession cell counts were highly
      reproducible for eosinophils (r = .7) for the second lavage. The two-tailed t
      test did not reveal any statistically significant differences between the good
      and the poor outcome groups. CONCLUSION: Assessment of eosinophil cell counts on
      sinus lavage is a feasible and reproducible method to evaluate the inflammatory
      state of a patient's sinuses in patients who have undergone ESS.

PMID- 15971653
TI  - Modified house tympanoplasty for successful closure of near-total tympanic
      membrane perforations.
AB  - OBJECTIVE: To demonstrate the use of a modified House technique in the successful
      closure of near-total tympanic membrane perforations. METHODS: This is a
      retrospective analysis over a 25-year span of the senior author's experience with
      a particular technique of closing large tympanic membrane perforations. The
      charts of patients were reviewed and the data were analyzed. TECHNIQUE: The
      modified House technique combines an underlay graft placement with an advancement
      ear canal skin flap. It provides vascularization and subsequent early
      epithelialization of a large perforation. RESULTS: In this series, the senior
      author operated on 46 patients. Forty-three patients had one ear operated on and
      three had bilateral surgery. The closure rate was 98% (48 of 49 ears). The one
      failure had a subsequent successful closure at a later date. CONCLUSION: This is
      a simple endaural technique that guarantees successful closure of near-total
      tympanic membrane perforations using locally available tragal perichondrium.

PMID- 15971654
TI  - An extra letter, care gets better? Informing general practitioners about planned
      surgery for head and neck cancer.
AB  - OBJECTIVE: To investigate how general practitioners (GPs) value an additional
      letter from the hospital. This so-called preadmission letter informs the GP about
      planned surgery for head and neck cancer in one of their patients. DESIGN:
      Prospective survey among GPs by means of a questionnaire attached to the
      preadmission letter. SETTING: Department of Otolaryngology and Head and Neck
      Surgery of a tertiary care centre in the Netherlands and 104 different GPs in
      primary care. PARTICIPANTS: All GPs of patients undergoing surgery for head and
      neck cancer received the preadmission letter during a 1-year study period. MAIN
      OUTCOME MEASURES: GPs' appreciation of the received preadmission letter, GPs'
      opinion on the content of the preadmission letter, and GPs' general opinion on
      information provided by our hospital. RESULTS: Of the 145 preadmission letters
      sent during the study year, 115 questionnaires were returned (response rate of
      79%). All GPs positively appreciated receiving the preadmission letter and
      considered its content relevant. They valued the letter, with a mean mark of 8.3
      on a 10-point scale. The majority of the GPs agreed that the preadmission letter
      allows them to provide better care. CONCLUSIONS: GPs highly appreciate an extra
      letter informing them about intended surgery for head and neck cancer in one of
      their patients. Despite the basic content of the preadmission letter (five items
      only), the majority of GPs consider the information sufficient. The results of
      this study have led to the implementation of the preadmission letter to GPs of
      head and neck cancer patients on a permanent basis in our institution.

PMID- 15971655
TI  - Environmental tobacco smoke in rats.
AB  - OBJECTIVE: We conducted this study to identify the effect of subchronic cigarette
      smoke inhalation on the vocal cord mucosa of the rat. DESIGN: Experimental study.
      SETTING: Department of Otolaryngology, School of Medicine, Karadeniz Technical
      University, Trabzon, Turkey METHODS: Twenty-four male Wistar rats were divided
      randomly into experimental and control groups. The experimental group of rats was
      exposed to cigarette smoke for 2 hours each day over 60 consecutive days, and the
      control group was treated in an identical fashion but was exposed only to room
      air. MAIN OUTCOME MEASURES: Transmission electron microscopic examination of the
      rat vocal cords. RESULTS: We found very high levels of plasma thiocyanate after
      exposure to smoke in the experimental group but no increase in the control group.
      In the experimental group, mean plasma thiocyanate concentrations of 3.7 +/- 0.5
      and 119 +/- 11.4 mmol/L were measured before and after exposure to tobacco smoke,
      respectively (p < .05). On the contrary, mean plasma thiocyanate levels of
      control rats were found to be 3.0 +/- 0.4 and 3.9 +/- 0.4 mmol/L, respectively,
      before and after exposure. In the experimental group, the epithelium covering the
      true vocal cords shows disturbed stratification. Some cells exhibit loss of
      desmosomal connections between cells and enlargement of the intercellular space.
      CONCLUSION: Our study demonstrates that the larynx in laboratory animals is one
      of the sensitive and useful targets for assessing the harmful effects associated
      with environmental tobacco smoke.

PMID- 15971656
TI  - Temporal bone measurements on high-resolution computed tomography.
AB  - The distances between the important neural and vascular structures in normal
      temporal bones were measured by using high-resolution computed tomography (HRCT).
      We examined 100 normal ears in 50 subjects ranging in age from 15 to 72 years
      (mean age 39 years). We measured the distances from the medial lip of the
      posterior wall of the internal auditory canal to the medial wall of the vestibule
      (mean 9.7 mm), from the cochlea to the tympanic segment of the facial canal (mean
      1.76 mm), from the medial wall of the vestibule to the lateral aspect of the
      lateral semicircular canal (mean 8.03 mm), and from the external auditory canal
      to the lateral sinus (mean 13.2 mm). HRCT examination is the best method for
      defining the morphology of temporal bone.

PMID- 15971657
TI  - Are all cookie-bite audiograms hereditary hearing loss?

PMID- 15971658
TI  - Tracheostomy during SARS.

PMID- 15971659
TI  - Castleman's disease of the parotid.

PMID- 15971660
TI  - Malignant melanoma of the external ear canal: a rare case.

PMID- 15971661
TI  - Post-tonsillectomy subcutaneous emphysema and pneumomediastinum.

PMID- 15971662
TI  - Atmospheric transport of metals.

PMID- 15971663
TI  - The marine biogeochemistry of iron.

PMID- 15971664
TI  - Speciation and bioavailability of trace metals in freshwater environments.

PMID- 15971665
TI  - Bioavailability and biogeochemistry of metals in the terrestrial environment.

PMID- 15971666
TI  - Heavy metal uptake by plants and cyanobacteria.

PMID- 15971667
TI  - Arsenic: its biogeochemistry and transport in groundwater.

PMID- 15971668
TI  - Anthropogenic impacts on the biogeochemistry and cycling of antimony.
AB  - Antimony is a potentially toxic trace element with no known biological function.
      Antimony is commonly enriched in coals, and fossil fuel combustion appears to be
      the largest single source of anthropogenic Sb to the global atmosphere. Abundant
      in sulfide minerals, its emission to the atmosphere from anthropogenic activities
      is linked to the mining and metallurgy of non-ferrous metals, especially Pb, Cu,
      and Zn. In particular, the geochemical and mineralogical association of Sb with
      Pb minerals implies that, like Pb, Sb has been emitted to the environment for
      thousands of years because of Pb mining, smelting, and refining. In the US alone,
      there are more than 400 former secondary lead smelting operations and worldwide
      there are 133 Pb-Zn smelters in operation today. Antimony is used in creating and
      improving dozens of industrial and commercial materials including various alloys,
      ceramics, glasses, plastics, and synthetic fabrics, making waste incineration
      another important source of Sb to the environment. Enrichments of Sb in
      atmospheric aerosols, plants, soils, sediments, as well as alpine and polar snow
      and ice suggest that Sb contamination is extensive, but there are very few
      quantitative studies of the geographic extent, intensity, and chronology of this
      contamination. There is an urgent need to quantify the extent of human impacts
      and how these have changed with time. The decreasing inventories of anthropogenic
      Sb with time in peat cores from Switzerland and Scotland suggest that the
      atmospheric Sb flux may be declining, but there have been too few studies to make
      any general conclusions. In fact, some studies of sediments and biomonitors in
      central Europe show little decline in Sb concentrations during the past decades.
      There is an obvious need for reliable data from well dated archives such as polar
      snow and ice, peat bogs, and sediments. The air concentrations, extent of
      enrichment, particle size distribution, and rate of deposition of Sb in urban
      areas is cause for concern. The natural processes which controlled the Sb flux to
      the atmosphere in the pre-anthropogenic past are poorly understood. The
      cumulative amount of anthropogenic Sb in soils has not yet been quantified. The
      long-term fate of Sb in soils, including weathering and mobilization, has only
      started to be investigated. However, the limited data available suggests that, in
      some locations at least, anthropogenic Sb in soils may be more mobile than
      anthropogenic Pb. Further study of this problem is needed, as well as the
      chemical speciation of Sb in soil-water-plant-sediment systems, and the
      implications which this has for human and ecosystem health.

PMID- 15971669
TI  - Microbial transformations of radionuclides: fundamental mechanisms and
      biogeochemical implications.

PMID- 15971670
TI  - Biogeochemistry of carbonates: recorders of past oceans and climate.
AB  - Trace metal proxies bound within the calcium carbonate tests of oceanic organisms
      provide a unique insight into how the climate system works on timescales which
      span eight orders of magnitude, from annual to hundreds of millions of years.
      Whilst the motivation for developing these proxies was the idea that
      thermodynamic equilibria control the chemistry during precipitation, in reality
      the application of trace metal proxies relies upon empirical calibration. Such
      calibration can be applied to a wide range of environmental reconstructions, but
      more accurate application of proxies requires a mechanistic understanding of the
      biomineralization process. The partitioning of trace metals into biogenic
      carbonates reflects to some extent the same pattern as an inorganic crystal, but
      there is an additional selectivity and differing environmental sensitivity to,
      e.g., temperature, which confirms that biochemical processes also play a role in
      the uptake and assembly of ions into a crystal. Different organisms display
      differing degrees of biological control on their carbonate chemistry. Aragonitic
      coral chemistry is most similar to inorganic precipitation from seawater whilst
      coccolithophores are most different, and these contrasts correlate with the
      degree of control of the organism over its biomineralization. Selectivity between
      Ca and trace metals during biomineralization arises during transport by pumps,
      channels, or nucleation upon an organic matrix. The biological selectivity of the
      transporters and matrix is strikingly similar in its base chemistry to the
      selective assembly of ions into a crystal. In each case, the selectivity between
      Ca2+ and trace metals derives from the balance between the energy required for
      dehydration of the hexaaqua complex of the cation, and the energy released from
      the new coordination geometry of binding with either carbonyl oxygen from
      polysaccharides or amino acids, or carbonate oxygen in the crystal. This is a
      speculative idea, but with some careful chemical calculations based on the energy
      of binding of Ca2+ or the trace metal ions to these macromolecular structures, it
      provides an alternative thermodynamic framework within which to consider the
      application of trace metal proxies.

PMID- 15971671
TI  - Development of improved method for isolation of Mycobacterium avium subsp.
      paratuberculosis from bulk tank milk: effect of age of milk, centrifugation, and
      decontamination.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of
      Johne's disease in cattle and it has been suggested that this organism may be
      associated with Crohn's disease in humans. Cows at the advanced stage of the
      disease shed this organism into both their milk and feces. The objective of this
      study was to develop a more efficient procedure for isolating MAP from bulk tank
      raw milk. Bulk tank raw milk (50 mL) samples 3 to 13 d old after collection
      without spiking were investigated to evaluate the effects of milk age on the
      efficacy of decontamination. Milk samples, 2 to 3 d old, were seeded with MAP at
      levels of 50 to 200 colony forming units/mL in experiments involving factorial
      design to evaluate 1) the effects of different decontaminating reagents and
      decontamination procedures on recovery of MAP, and 2) partition MAP in milk
      fractions after centrifugation in raw milk. Decontamination in 20 mL of 0.75%
      hexadecylpyridinium chloride (HPC) at room temperature (22 degrees C) for 2 to 5
      h, with shaking, at intervals was found to be the most effective procedure for
      decontaminating milk 2 to 3 d old. Prolonged exposure to decontaminants,
      additional incubations in antibiotics, or at higher temperature (37 degrees C)
      significantly reduced recovery of live MAP. Enhanced growth of microbial
      contaminants was noticed in samples decontaminated overnight at room temperature
      compared to those decontaminated for 2 to 5 h. Decontamination of 6 d old milk
      samples required extra incubation in antibiotic brew. Decontamination of milk
      samples that are 8 d and older was not effective in removing microbial
      contaminants. The MAP cells preferentially partitioned into the cream fraction
      after centrifugation, and combining the milk cream and pellet fractions enhanced
      recovery of MAP. A recovery rate of 16.6% was estimated with the use of our
      improved protocol.

PMID- 15971672
TI  - A temporal study of Salmonella serovars in animals in Alberta between 1990 and
      2001.
AB  - Passive laboratory-based surveillance data from Alberta Agriculture Food and
      Rural Development were analyzed for common Salmonella serovars, prevalences,
      trends, and for the presence of temporal clusters. There were 1767 isolates
      between October 1990 and December 2001 comprising 63 different serovars,
      including 961 isolates from chickens, 418 from cattle, 108 from pigs, 102 from
      turkeys, and 178 from all other species combined. Salmonella Typhimurium,
      Heidelberg, Hadar, Kentucky, and Thompson were the 5 most frequently isolated
      serovars. Approximately 60% of the S. Typhimurium were isolated from cattle,
      whereas over 90% of the S. Heidelberg, Hadar, Kentucky, and Thompson were
      isolated from chickens. Salmonella Enteritidis was rarely isolated. There was an
      increasing trend in isolates from chickens, cattle, and pigs, and a decreasing
      trend in isolates from turkeys. Temporal clusters were observed in 11 of 15
      serovars examined in chickens (S. Anatum, Heidelberg, Infantis, Kentucky,
      Mbandaka, Montevideo, Nienstedten, Oranienburg, Thompson, Typhimurium, and
      Typhimurium var. Copenhagen), 5 of 5 serovars in cattle (S. Dublin, Montevideo,
      Muenster, Typhimurium, and Typhimurium var. Copenhagen), and 1 of 3 serovars in
      pigs (S. Typhimurium). Short-duration clusters may imply point source infections,
      whereas long-duration clusters may indicate an increase in the prevalence of the
      serovar, farm-to-farm transmission, or a wide-spread common source. A higher
      concentration of clusters in the winter months may reflect greater confinement,
      reduced ventilation, stressors, or increased exposure to wildlife vectors that
      are sharing housing during the winter. Detection of large clusters of Salmonella
      may have public health implications in addition to animal health concerns.

PMID- 15971673
TI  - Recombinant rabies virus vaccine strain SAD-l16 inoculated intracerebrally in
      young mice produces a severe encephalitis with extensive neuronal apoptosis.
AB  - Seven-day-old ICR mice were infected by intracerebral inoculation with
      recombinant rabies virus vaccine strain SAD-L16. Infected mice developed severe
      and fatal encephalitis with rabies virus-infected neurons in widespread regions
      of the brain. There was extensive neuronal death with predominant features of
      apoptosis, as assessed by light and electron microscopy, terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)
      staining, and immunohistochemical staining for activated caspase-3. Although SAD
      L16 is a neuroattenuated rabies virus, it is fully capable of spreading
      efficiently and inducing widespread neuronal apoptosis in the immature mouse
      brain.

PMID- 15971674
TI  - Detection and comparison of nitric oxide in clinically healthy horses and those
      with naturally acquired strangulating large colon volvulus.
AB  - The objective of the study was to determine whether nitric oxide (NO) is present
      in clinically healthy horses (control) under basal conditions, and if it
      increases secondary to naturally acquired strangulating large colon volvulus
      (affected). Eleven affected horses and 10 controls were studied. Jugular venous
      blood, abdominal fluid, and urine were collected. The NO concentrations were
      standardized to the creatinine concentration in the respective samples. A biopsy
      specimen collected from the large colon pelvic flexure at surgery was divided
      into subsections for processing for inducible nitric synthase (iNOS) and
      nitrotyrosine (NT) immunohistochemical staining and reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) diaphorase histochemical staining. There were no
      significant differences in plasma, abdominal fluid, or urine NO concentrations
      between affected and control horses. There was a significant decrease in
      submucosal arteriolar and venular endothelium, submucosal plexus, mucosal
      leukocyte, mucosal and musclaris vasculature, and myenteric plexus NADPH
      diaphorase staining in affected versus control horses. There was a significant
      increase in iNOS staining in mucosal leukocytes and vasculature in affected
      versus control horses. Other than a greater number of positively stained mucosal
      leukocytes in affected horses, there were no significant differences between
      affected and control horses for NT staining. The presence of NADPH diaphorase
      staining in the endothelium and submucosal neurons suggests endothelial and
      neuronal NOS are present under basal conditions in the large colon of horses.
      Increased iNOS and NT staining in mucosal leukocytes of affected horses suggests
      involvement of the NO pathway in large colon volvulus. The reasons for the lack
      of a significant difference in plasma, abdominal fluid, and urine NO
      concentrations between affected and control horses are unknown.

PMID- 15971675
TI  - Role of endothelium and nitric oxide in modulating in vitro responses of colonic
      arterial and venous rings to vasodilatory neuropeptides in horses.
AB  - The objective of this study was to determine and compare the in vitro responses
      of equine large colon arterial and venous rings to vasodilatory neuropeptides;
      calcitonin gene-related peptide (CGRP); substance P (SP); vasoactive intestinal
      polypeptide (VIP); and acetylcholine (ACh), a standard nonpeptide endothelium
      dependent vasodilator. Responses of vessel rings to graded concentrations (10(
      11) M to 10(-5) M) of each drug were determined in endothelium-intact, denuded,
      and Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M)-treated rings that
      were pre-contracted with norepinephrine. Percentage maximal relaxation (PMR),
      defined as the % decrease from the contracted state, was determined. Because all
      rings did not relax at least 50%, EC50 values could not be consistently
      calculated. Arterial rings with intact endothelium were more sensitive to CGRP,
      compared with VIP and SP, and venous rings of all conditions were more sensitive
      to VIP than CGRP or SP. Overall, arteries had a greater PMR for ACh compared with
      SP and VIP. Intact and L-NAME treated arteries had a greater PMR than denuded
      arteries; there were no differences in PMR of intact and L-NAME treated arteries.
      Veins had a greater PMR for VIP than CGRP, SP, or ACh. Calcitonin gene-related
      peptide caused greater relaxation in intact arteries, whereas VIP causes greater
      relaxation in veins. Arterial relaxation was dependent upon the presence of
      intact endothelium. The response of veins to VIP among the conditions tested was
      not different, suggesting VIP has direct actions on venous smooth muscle. These
      neuropeptides modulate vasomotor tone via vasorelaxation in colonic arteries and
      veins.

PMID- 15971676
TI  - Detection of silver protein complex injections in the bovine udder using X-ray
      fluorescence: a preliminary investigation.
AB  - To determine the feasibility of using x-ray fluorescence (XRF) to detect the
      presence of silver in the mammary gland of dairy cows injected with mild silver
      protein suspension. The XRF spectroscopy was conducted on cadaver udders with and
      without mild silver protein injected. Spectral analysis was performed in order to
      determine the amplitude of the silver K-alpha peak that was detected. By
      comparing the amplitude of the K-alpha peak to the background, a minimum time of
      collection was determined, as a measure of the time required to observe a silver
      signal that is significantly non-zero. The minimum detection time required for
      evidence of injected silver suspension was calculated to be 2.8 +/- 0.2 s. Even
      with an additional requirement that the net signal exceed 50 counts, the clear
      indication of the presence of silver will be observed within 4 min of
      interrogation. X-ray fluorescence spectroscopy was shown to be a viable method
      for the detection of injected silver protein in cadaver mammary glands of dairy
      cows. While these findings are promising, further studies must be conducted to
      investigate the time dependence of the silver signal when diffusion, absorption,
      and redistribution are involved, under conditions that better mimic those
      encountered at an exhibition. This technique, used in conjunction with screening
      ultrasound examinations, has the potential to confirm sites of injection of
      silver compounds.

PMID- 15971677
TI  - Radiographic evaluation of destructive periodontal disease in blue mink in
      relation to age and blood morphology.
AB  - In this study, blood samples and jaws were collected from 2 genotypes of blue
      mink (n = 289) in order to examine phenotypic expression of specific
      characteristics of Chediak-Higashi Syndrome (C-HS). Blood samples were subjected
      to differential counts to assess the proportion of abnormal polymorphonuclear
      leukocytes characteristic for CH-S (C-HS-leukocytes). Abnormal leukocytes with
      characteristic signs of C-HS were found in blood smears from all mink included in
      this study. Four teeth in one half of the mandible (P3, P4, M1, M2) were
      subjected to quantitative radiographic evaluation of alveolar bone loss and tooth
      loss. There was a high prevalence of destructive periodontal disease among blue
      mink included in this study. Mild to moderate periodontal disease (defined by
      less than 50% alveolar bone loss related to 1 or more teeth) affected 73.7% of
      young mink (age = 7 mo) and 67.9% of older animals (age > or = 19 mo). Severe
      periodontal disease (defined by more than 50% bone loss related to one or more
      teeth) was not detected in mink aged 7 mo, but affected 15.3% of mink aged 19 mo
      and 39.6% of mink aged 31 mo. The positive relationship between age and
      periodontal disease was statistically significant (P < 0.01). The prevalence of
      tooth loss was found to be high among blue mink aged > 19 mo (21.6%) and was also
      significantly related to age (P < 0.01). A significant positive interaction
      between alveolar bone loss and tooth loss (P < 0.01), implies that the highly
      prevalent tooth loss in the mink was related to and possibly caused by
      destructive periodontal disease. There was no significant difference in the
      prevalence of periodontal disease between the 2 genotypes and age was found to be
      the only statistical predictor of poor production results (P < 0.01) in blue
      mink.

PMID- 15971678
TI  - Delayed vaccine virus replication in chickens vaccinated subcutaneously with an
      immune complex infectious bursal disease vaccine: quantification of vaccine virus
      by real-time polymerase chain reaction.
AB  - The distribution of the immune complex vaccine virus for infectious bursal
      disease (IBD) in tissue was examined and the viral loads of the organs were
      quantitatively compared. One-day-old specific pathogen free (SPF) and maternally
      immune broiler chickens were injected subcutaneously with the vaccine. Lymphoid
      and non-lymphoid tissues were collected at various time intervals during the
      experiment to test for infectious bursal disease virus (IBDV)-RNA by using
      reverse transcriptase-polymerase chain reaction (RT-PCR). Only the bursa of
      Fabricius was found to be positive with unusually long viral persistence in the
      broiler group. The positive bursa samples were further investigated by using real
      time PCR coupled with a TaqMan probe. The highest amounts of the virus were
      detected at its first appearance in the bursa: on day 14 post vaccination (PV) in
      the SPF chickens and on day 17 and day 21 PV in the maternally immune broiler
      group. The virus then gradually cleared, most likely due to the arallel
      appearance of the active immune response indicated by seroconversion.

PMID- 15971679
TI  - Spoligotyping of Mycobacterium bovis isolates found in Manitoba.
AB  - Spoligotyping was applied to 44 isolates of Mycobacterium bovis obtained from the
      Canadian province of Manitoba. Isolates were obtained from submissions of elk (n
      = 16), deer (n = 1), and cattle (n = 27) tissues spanning the period of 1990 to
      early 2003. Two spoligotype profiles were obtained differing only in the reaction
      with oligonucleotide number 12. Forty of the 44 isolates (90.9%) hybridized with
      oligonucleotide 12 (MB-1 type), while the remaining 4 of 44 (9.1%) did not show a
      signal at position 12 (MB-2 type). Octal codes for these 2 types are
      656573377603600 and 656473377603600, respectively. These spoligotypes have not
      been reported as occurring elsewhere worldwide.

PMID- 15971680
TI  - Assessment of the efficacy of tilmicosin phosphate to eliminate Actinobacillus
      pleuropneumoniae from carrier pigs.
AB  - The aim of this study was to evaluate the efficacy of in-feed medication with
      tilmicosin phosphate in order to eliminate or reduce the carriage of
      Actinobacillus pleuropneumoniae in the tonsils of carrier pigs. Two groups of 6
      carrier animals received either a non-medicated feed (control group) or feed
      medicated with 400 ppm of tilmicosin phosphate (treated group) for 30 d. Three
      sentinel pigs were then introduced in each group and left for 29 d. The presence
      of A. pleuropneumoniae in tonsils was monitored using several techniques,
      including polymerase chain reaction (PCR). At the end of the treatment all of the
      control animals, but only 1 treated pig, were positive by PCR from tonsillar
      surface material. However, at necropsy, all control and most treated animals, as
      well as 1 sentinel animal, in both groups were positive by PCR from whole
      tonsils. In conclusion, under the experimental conditions, in-feed treatment with
      400 ppm of tilmicosin phosphate significantly reduced the presence of A.
      pleuropneumoniae on the surface of tonsils but was unable to completely eliminate
      the organism from deeper tonsillar tissues and to prevent bacterial shedding by
      carrier animals.

PMID- 15971681
TI  - Production of ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha,
      interleukin-1beta, and interleukin-6 is suppressed by trans-resveratrol in a
      concentration-dependent manner.
AB  - Trans-resveratrol is a biologically active compound present in certain foods that
      has anti-inflammatory and anticancer properties. These beneficial effects are
      derived from both the immune system and cytokines. The purpose of this study was
      to determine the immunomodulatory effect of trans-resveratrol on the ex vivo
      production of inflammatory and anti-inflammatory cytokines stimulated by
      lipopolysaccharides (LPS). Trans-resveratrol (0, 0.01, 0.1, 1, and 10 microM) was
      added to blood samples from male Sprague-Dawley rats (n = 6) along with 100 U of
      LPS (Escherichia coli serotype, 055B5). The samples were then incubated for 4 h
      at 37 degrees C and centrifuged. Finally, concentrations of tumor necrosis factor
      alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the plasma were
      analyzed using an enzyme-linked immunosorbent assay (ELISA). The production of
      inflammatory (TNF-alpha and IL-1beta) and anti-inflammatory (IL-6) cytokines was
      suppressed by trans-resveratrol in a concentration-dependent manner. These
      results support the hypothesis that the immunomodulatory effect of trans
      resveratrol plays an important role in disease conditions that involve an
      overproduction of inflammatory cytokines.

PMID- 15971682
TI  - Quantities and types of ceramides and their relationships to physical properties
      of the horn covering the claws of clinically normal cows and cows with
      subclinical laminitis.
AB  - Quantities and types of ceramides and their relationships to physical properties
      of the horn covering the claws of clinically normal cows and cows with
      subclinical laminitis were investigated. Total ceramide content of the horn
      covering the sole and wall from cows with subclinical laminitis was 872.2 +/-
      146.6 microg/g and 528.6 +/- 61.3 microg/g, respectively, and was significantly
      (P < 0.01, 0.05) lower than that from clinically normal cows. The mean moisture
      content in the claws from cows with subclinical laminitis (43.5% +/- 4.3%) was
      significantly (P < 0.05) higher than that in the claws from clinically normal
      cows. The hardness of claws from cows with subclinical laminitis (35.2 +/- 3.5)
      was significantly (P < 0.05) less than that of claws from clinically normal cows.
      Significant correlations between ceramides and moisture content (P < 0.001) and
      between ceramide and hardness (P < 0.001) were found in clinically normal cows
      and cows with subclinical laminitis. Our results indicate that decreases in
      ceramide contents may be related to changes in physical properties of the horn
      covering the claw in cows with subclinical laminitis.

PMID- 15971683
TI  - Remembering "what" brings along "where" in visual working memory.
AB  - Does a behavioral and anatomical division exist between spatial and object
      working memory? In this article, we explore this question by testing human
      participants in simple visual working memory tasks. We compared a condition in
      which there was no location change with conditions in which absolute location
      change and absolute plus relative location change were manipulated. The results
      showed that object memory was influenced by memory for relative but not for
      absolute location information. Furthermore, we demonstrated that relative space
      can be specified by a salient surrounding box or by distractor objects with no
      touching surfaces. Verbal memory was not influenced by any type of spatial
      information. Taken together, these results indicate that memory for "where"
      influences memory for "what." We propose that there is an asymmetry in memory
      according to which object memory always contains location information.

PMID- 15971684
TI  - Attentional and perceptual sources of the auditory attentional blink.
AB  - When a rapid succession of auditory stimuli is listened to, processing of the
      second of two successive targets among fillers is often impaired, a phenomenon
      known as the attentional blink (AB). Three experiments were conducted to examine
      the role of filler items in modulating the size of the auditory AB, using a two
      alternative forced choice discrimination paradigm. In the first experiment, dual
      stream presentations in which low- and high-pitch items were separated by six
      semitones were tested. A transient deficit in reporting the probe was observed in
      the presence of fillers that was greater when fillers were in the same stream as
      the probe. In the absence of a filler, there was a residual deficit, but this was
      not related to the time lag between the target and the probe. In the second and
      third experiments, in which single-stream presentations were used, a typical AB
      was found in the presence of homogeneous fillers, but heterogeneous fillers
      tended to produce a greater deficit. In the absence of a filler, there was little
      or no evidence of a blink. The pattern of results suggests that other attentional
      and perceptual factors contribute to the blink.

PMID- 15971685
TI  - The phantom illumination illusion.
AB  - A novel brightness illusion in planar patterns is reported. The illusion occurs,
      for example, when surfaces with a luminance ramp shaded from black to white are
      positioned on a black homogeneous background, so that each white end of the
      surfaces faces a single point of the plane of the pattern. The illusion consists
      of the enhancement of the brightness of the background in a relatively wide area
      around the white ends of the surfaces. A parametric study was conducted in which
      participants were asked to rate the difference in brightness between the parts of
      the background inside and outside a virtual circle formed by disks with different
      luminance ramps. The results show that mean ratings of brightness depended on the
      luminance of the background, the luminance range of ramps, and the kind of ramp.
      Discussion of these results with reference to other brightness illusions
      (assimilation, neon color spreading, anomalous surfaces, visual phantoms, grating
      induction, and the glare effect) shows that t hephantom illumination illusion
      derives from processes producing the perception of ambient illumination.

PMID- 15971686
TI  - The onset of receding motion captures attention: comment on Franconeri and Simons
      (2003).
AB  - Franconeri & Simons (2003) reported that some but not all types of motion capture
      attention in a visual search task, ostensibly because some types of motion are
      behaviorally significant. In the present article, we argue that a more
      parsimonious explanation of their results is that the onset of motion, but not
      motion per se, captures attention. This conclusion helps to resolve
      inconsistencies between the Franconeri and Simons findings and earlier reports
      from other investigators and is consistent with results that we have recently
      reported (Abrams & Christ, 2003). The Franconeri and Simons interpretation rests
      largely on their failure to find attentional capture by one type of motion
      simulated receding motion. We report here the results of two experiments that
      demonstrate that the onset of receding motion does indeed capture attention when
      the motion is produced using stereo depth cues. As we have argued elsewhere, the
      capture of attention in displays containing motion appears to be dependent on the
      onset of the motion, rather than on the mere presence of specific types of motion
      as suggested by Franconeri and Simons. One possible explanation is that the onset
      of motion captures attention because it serves as a strong cue to animacy--and
      the detection of nearby animals can have important consequences for survival.

PMID- 15971687
TI  - The specificity of perceptual learning in speech processing.
AB  - We conducted four experiments to investigate the specificity of perceptual
      adjustments made to unusual speech sounds. Dutch listeners heard a female talker
      produce an ambiguous fricative [?] (between [f] and [s]) in [f]- or [s]-biased
      lexical contexts. Listeners with [f]-biased exposure (e.g., [witlo?]; from
      witlof, "chicory"; witlos is meaningless) subsequently categorized more sounds on
      an [epsilonf]-[epsilons] continuum as [f] than did listeners with [s]-biased
      exposure. This occurred when the continuum was based on the exposure talker's
      speech (Experiment 1), and when the same test fricatives appeared after vowels
      spoken by novel female and male talkers (Experiments 1 and 2). When the continuum
      was made entirely from a novel talker's speech, there was no exposure effect
      (Experiment 3) unless fricatives from that talker had been spliced into the
      exposure talker's speech during exposure (Experiment 4). We conclude that
      perceptual learning about idiosyncratic speech is applied at a segmental level
      and is, under these exposure conditions, talker specific.

PMID- 15971688
TI  - Efficient visual search without top-down or bottom-up guidance.
AB  - Two types of mechanisms have dominated theoretical accounts of efficient visual
      search. The first are bottom-up processes related to the characteristics of
      retinotopic feature maps. The second are top-down mechanisms related to feature
      selection. To expose the potential involvement of other mechanisms, we introduce
      a new search paradigm whereby a target is defined only in a context-dependent
      manner by multiple conjunctions of feature dimensions. Because targets in a
      multiconjunction task cannot be distinguished from distractors either by bottom
      up guidance or top-down guidance, current theories of visual search predict
      inefficient search. While inefficient search does occur for the multiple
      conjunctions of orientation with color or luminance, we find efficient search for
      multiple conjunctions of luminance/size, luminance/shape, and luminance/topology.
      We also show that repeated presentations of either targets or a set of
      distractors result in much faster performance and that bottom-up feature
      extraction and top-down selection cannot account for efficient search on their
      own. In light of this, we discuss the possible role of perceptual organization in
      visual search. Furthermore, multiconjunction search could provide a new method
      for investigating perceptual grouping in visual search.

PMID- 15971689
TI  - Equating tasks and sustaining attention in children and adults: the
      methodological and theoretical utility of d' matching.
AB  - The present study develops a method to create task equivalency for children and
      adults in vigilance research. Experiment 1 employed the signal detection index of
      perceptual sensitivity (d') to calibrate vigilance tasks for 32 children (ages 7
      8) and 32 adults. The results of Experiment 1 suggest that task equivalency
      across groups can be attained, and a vigilance decrement was observed for
      children. In Experiment 2, the task parameter of event rate was manipulated
      across two vigils. Again, 32 children (ages 7-8) and 32 adults participated. The
      results suggest that a reverse event rate effect emerged for both children and
      adults. In addition, developmental differences in response to the event rate
      manipulation and with respect to the vigilance decrement emerged: Children
      benefited less from the manipulation and were more likely to demonstrate a
      vigilance decrement than were adults. No developmental differences emerged for
      the sensitivity decrement. The results are explained with reference to how task
      demands interact with participant arousal, and implications for development and
      for future research are discussed.

PMID- 15971690
TI  - A comparison of length-matching and length-fractionation measures of Muller-lyer
      distortions.
AB  - Two experiments were performed to evaluate the informational equivalence of
      length-matching (e.g., reproduction) and length-fractionation (e.g., bisection)
      procedures that are frequently used to quantify geometrical size distortions,
      such as the Muller-Lyer (M-L) illusion. In Experiment 1, the distortion in the
      apparent length of a horizontal test line was measured as a function of the angle
      between it and an abutting inducing line, and in Experiment 2 distortion was
      measured in the apparent length of the shaft of one-angle versions of the M-L
      illusion. Both procedures indexed the expansion of the obtuse-angle and the wings
      out M-L illusion and the contraction of the acute-angle and the wings-in M-L
      illusion. However, whereas the reproduction measures indicated substantially
      greater expansion than contraction distortion, the bisection measures indicated
      greater contraction distortion. Some possible reasons for this difference,
      particularly the possibility that the reproduction and bisection procedures are
      unequally sensitive to the outputs of the mechanisms producing the M-L illusion,
      are discussed.

PMID- 15971691
TI  - Do we hear size or sound? Balls dropped on plates.
AB  - The aim of this study is to examine whether it is possible to recover directly
      the size of an object from the sound of an impact. Specifically, the study is
      designed to investigate whether listeners can tell the size of a ball from the
      sound when it is dropped on plates of different diameters (on one, two, or three
      plates in Experiments 1, 2, and 3, respectively). In this paradigm, most of the
      sound produced is from the plate rather than the ball. Listeners were told
      neither how many different balls or plates were used nor the materials of the
      balls and plates. Although listeners provided reasonable ball size estimates,
      their judgments were influenced by the size of the plate: Balls were judged to be
      larger when dropped on larger plates. Moreover, listeners were generally unable
      to recognize either ball and plate materials or the number of plates used in
      Experiments 2 and 3. Finally, various acoustic properties of the sounds are shown
      to be correlated with listeners' judgments.

PMID- 15971692
TI  - Inhibition and decay of motor and nonmotor priming.
AB  - Motor responses can be facilitated by congruent visual stimuli and prolonged by
      incongruent visual stimuli that are made invisible by masking (direct motor
      priming). Recent studies on direct motor priming showed a reversal of these
      priming effects when a three-stimulus paradigm was used in which a prime was
      followed by a mask and a target stimulus was presented after a delay. A similar
      three-stimulus paradigm on nonmotor priming, however, showed no reversal of
      priming effects when the mask was used as a cue for processing of the following
      target stimulus (cue priming). Experiment 1 showed that the time interval between
      mask and target is crucial for the reversal of priming. Therefore, the time
      interval between mask and target was varied in three experiments to see whether
      cue priming is also subject to inhibition at a certain time interval. Cues
      indicated (1) the stimulus modality of the target stimulus, (2) the task to be
      performed on a multidimensional auditory stimulus, or (3) part of the motor
      response. Whereas direct motor priming showed the reversal of priming about 100
      msec after mask presentation, cue priming effects simply decayed during the 300
      msec after mask presentation. These findings provide boundary conditions for
      accounts of inverse priming effects.

PMID- 15971693
TI  - The frequency effect for pseudowords in the lexical decision task.
AB  - Four experiments were designed to investigate whether the frequency of words used
      to create pseudowords plays an important role in lexical decision. Computational
      models of the lexical decision task (e.g., the dual route cascaded model and the
      multiple read-out model) predict that latencies to low-frequency pseudowords
      should be faster than latencies to high-frequency pseudowords. Consistent with
      this prediction, results showed that when the pseudowords were created by
      replacing one internal letter of the base word (Experiments 1 and 3), high
      frequency pseudowords yielded slower latencies than low-frequency pseudowords.
      However, this effect occurred only in the leading edge of the response time (RT)
      distributions. When the pseudowords were created by transposing two adjacent
      internal letters (Experiment 2), high-frequency pseudowords produced slower
      latencies in the leading edge and in the bulk of the RT distributions. These
      results suggest that transposed-letter pseudowords may be more similar to their
      base words than replacement-letter pseudowords. Finally, when participants
      performed a go/no-go lexical decision task with one-letter different pseudowords
      (Experiment 4), high-frequency pseudowords yielded substantially faster latencies
      than low-frequency pseudowords, which suggests that the lexical entries of high
      frequency words can be verified earlier than the lexical entries of low-frequency
      words. The implications of these results for models of word recognition and
      lexical decision are discussed.

PMID- 15971694
TI  - Contributions of temporal and place cues in pitch perception in absolute pitch
      possessors.
AB  - Pitch perception is determined by both place and temporal cues. To explore
      whether the manner in which these cues are used differs depending on absolute
      pitch capability, pitch identification experiments with and without pitch
      references were conducted for subjects with different absolute pitch capabilities
      and musical experience. Three types of stimuli were used to manipulate place and
      temporal cues separately: narrowband noises, which provide strong place cues but
      less salient temporal cues; iterated rippled noises, which provide strong
      temporal cues but less salient place cues; and sinusoidal tones, which provide
      both. The results indicated that absolute pitch possessors utilize temporal cues
      more effectively when they identify musical chroma With regard to the judgment of
      height, it was indicated that place cues play an important role for both absolute
      and nonabsolute pitch possessors.

PMID- 15971695
TI  - Intermittent visual information and the multiple time scales of visual motor
      control of continuous isometric force production.
AB  - In an experiment, we examined the effect of intermittency (from 25.6 Hz to 0.2
      Hz) of visual information on continuous isometric force production as a function
      of force level (5%, 10%, 25%, and 50% of maximal voluntary contraction [MVC]).
      The amount of force variability decreased and the irregularity of force output
      increased as a function of increased visual intermittency rate. Vision was found
      to have an influence on the frequency structure of force output up to 12 Hz, and
      the 25% MVC force level had more high-frequency modulations with higher rates of
      visual information. The effective use of intermittent visual information is
      mediated nonlinearly by force level, and there are multiple time scales of visual
      control (range, approximately 0 - 12 Hz) that are postulated to be a function of
      both feedback and feedforward control processes.

PMID- 15971696
TI  - A spatial explanation for synchrony biases in perceptual grouping: consequences
      for the temporal-binding hypothesis.
AB  - If two images are shown in rapid sequential order, they are perceived as a
      single, fused image. Despite this, recent studies have revealed that fundamental
      perceptual processes are influenced by extremely brief temporal offsets in
      stimulus presentation. Some researchers have suggested that this is due to the
      action of a cortical temporal-binding mechanism, which would serve to keep
      multiple mental representations of one object distinct from those of other
      objects. There is now gathering evidence that these studies should be reassessed.
      This article describes evidence for sensitivity to fixational eye and head
      movements, which provides a purely spatial explanation for the earlier results.
      Taken in conjunction with other studies, the work serves to undermine the current
      body of behavioral evidence for a temporal-binding mechanism.

PMID- 15971697
TI  - Subordinate-level categorization relies on high spatial frequencies to a greater
      degree than basic-level categorization.
AB  - In two experiments, category verification of images of common objects at
      subordinate, basic, and superordinate levels was performed after low-pass spatial
      filtering, high-pass spatial filtering, 50% phase randomization, or no image
      manipulation. Both experiments demonstrated the same pattern of results: Low-pass
      filtering selectively impaired subordinate-level category verification, while
      having little to no effect on basic-level category verification. Subordinate
      categorization consequently relies to a greater degree on high spatial
      frequencies of images. This vulnerability of subordinate-level processing was
      specific to a lack of high spatial frequency information, as opposed to other
      visual information, since neither high-pass filtering nor the addition of phase
      noise produced a comparable reduction in performance. These results are
      consistent with the notion that object recognition at basic levels relies on the
      general shapes of objects, whereas recognition at subordinate levels relies on
      finer visual details.

PMID- 15971698
TI  - Damage rate is a predictor of fatigue life and creep strain rate in tensile
      fatigue of human cortical bone samples.
AB  - We present results on the growth of damage in 29 fatigue tests of human femoral
      cortical bone from four individuals, aged 53-79. In these tests we examine the
      interdependency of stress, cycles to failure, rate of creep strain, and rate of
      modulus loss. The behavior of creep rates has been reported recently for the same
      donors as an effect of stress and cycles. In the present paper we first examine
      how the evolution of damage (drop in modulus per cycle) is associated with the
      stress level or the "normalized stress" level (stress divided by specimen
      modulus), and results show the rate of modulus loss fits better as a function of
      normalized stress. However, we find here that even better correlations can be
      established between either the cycles to failure or creep rates versus rates of
      damage than any of these three measures versus normalized stress. The data
      indicate that damage rates can be excellent predictors of fatigue life and creep
      strain rates in tensile fatigue of human cortical bone for use in practical
      problems and computer simulations.

PMID- 15971699
TI  - Cellular cross-linking of peptide modified hydrogels.
AB  - Peptide modification of hydrogel-forming materials is being widely explored as a
      means to regulate the phenotype of cells immobilized within the gels.
      Alternatively, we hypothesized that the adhesive interactions between cells and
      peptides coupled to the gel-forming materials would also enhance the overall
      mechanical properties of the gels. To test this hypothesis, alginate polymers
      were modified with RGDSP-containing peptides and the resultant polymer was used
      to encapsulate C2C12 myoblasts. The mechanical properties of these gels were then
      assessed as a function of both peptide and cell density using compression and
      tensile tests. Overall, it was found that above a critical peptide and cell
      density, encapsulated myoblasts were able to provide additional mechanical
      integrity to hydrogels composed of peptide-modified alginate. This occurred
      presumably by means of cell-peptide cross-linking of the alginate polymers, in
      addition to the usual Ca++ cross-linking. These results are potentially
      applicable to other polymer systems and important for a range of tissue
      engineering applications.

PMID- 15971700
TI  - Mechanics of curved plasma membrane vesicles: resting shapes, membrane curvature,
      and in-plane shear elasticity.
AB  - Highly curved cell membrane structures, such as plasmalemmal vesicles (caveolae)
      and clathrin-coated pits, facilitate many cell functions, including the
      clustering of membrane receptors and transport of specific extracellular
      macromolecules by endothelial cells. These structures are subject to large
      mechanical deformations when the plasma membrane is stretched and subject to a
      change of its curvature. To enhance our understanding of plasmalemmal vesicles we
      need to improve the understanding of the mechanics in regions of high membrane
      curvatures. We examine here, theoretically, the shapes of plasmalemmal vesicles
      assuming that they consist of three membrane domains: an inner domain with high
      curvature, an outer domain with moderate curvature, and an outermost flat domain,
      all in the unstressed state. We assume the membrane properties are the same in
      these domains with membrane bending elasticity as well as in-plane shear
      elasticity. Special emphasis is placed on the effects of membrane curvature and
      in-plane shear elasticity on the mechanics of vesicle during unfolding by
      application of membrane tension. The vesicle shapes were computed by minimization
      of bending and in-plane shear strain energy. Mechanically stable vesicles were
      identified with characteristic membrane necks. Upon stretch of the membrane, the
      vesicle necks disappeared relatively abruptly leading to membrane shapes that
      consist of curved indentations. While the resting shape of vesicles is
      predominantly affected by the membrane spontaneous curvatures, the membrane shear
      elasticity (for a range of values recorded in the red cell membrane) makes a
      significant contribution as the vesicle is subject to stretch and unfolding. The
      membrane tension required to unfold the vesicle is sensitive with respect to its
      shape, especially as the vesicle becomes fully unfolded and approaches a relative
      flat shape.

PMID- 15971701
TI  - Viscoelastic properties of single attached cells under compression.
AB  - The viscoelastic properties of single, attached C2C12 myoblasts were measured
      using a recently developed cell loading device. The device allows global
      compression of an attached cell, while simultaneously measuring the associated
      forces. The viscoelastic properties were examined by performing a series of
      dynamic experiments over two frequency decades (0.1-10 Hz) and at a range of
      axial strains (approximately 10-40%). Confocal laser scanning microscopy was used
      to visualize the cell during these experiments. To analyze the experimentally
      obtained force-deformation curves, a nonlinear viscoelastic model was developed.
      The nonlinear viscoelastic model was able to describe the complete series of
      dynamic experiments using only a single set of parameters, yielding an elastic
      modulus of 2120 +/- 900 Pa for the elastic spring, an elastic modulus of 1960 +/-
      1350 for the nonlinear spring, and a relaxation time constant of 0.3 +/- 0.12 s.
      To our knowledge, it is the first time that the global viscoelastic properties of
      attached cells have been quantified over such a wide range of strains.
      Furthermore, the experiments were performed under optimal environmental
      conditions and the results are, therefore, believed to reflect the viscoelastic
      mechanical behavior of cells, such as would be present in vivo.

PMID- 15971702
TI  - PIV measurements of flow in a centrifugal blood pump: steady flow.
AB  - Magnetically suspended left ventricular assist devices have only one moving part,
      the impeller. The impeller has absolutely no contact with any of the fixed parts,
      thus greatly reducing the regions of stagnant or high shear stress that surround
      a mechanical or fluid bearing. Measurements of the mean flow patterns as well as
      viscous and turbulent stresses were made in a shaft-driven prototype of a
      magnetically suspended centrifugal blood pump at several constant flow rates (3-9
      L/min) using particle image velocimetry (PIV). The chosen range of flow rates is
      representative of the range over which the pump may operate while implanted.
      Measurements on a three-dimensional measurement grid within several regions of
      the pump, including the inlet, blade passage, exit volute, and diffuser are
      reported. The measurements are used to identify regions of potential blood damage
      due to high shear stress and/or stagnation of the blood, both of which have been
      associated with blood damage within artificial heart valves and diaphragm-type
      pumps. Levels of turbulence intensity and Reynolds stresses that are comparable
      to those in artificial heart valves are reported. At the design flow rate (6
      L/min), the flow is generally well behaved (no recirculation or stagnant flow)
      and stress levels are below levels that would be expected to contribute to
      hemolysis or thrombosis. The flow at both high (9 L/min) and low (3 L/min) flow
      rates introduces anomalies into the flow, such as recirculation, stagnation, and
      high stress regions. Levels of viscous and Reynolds shear stresses everywhere
      within the pump are below reported threshold values for damage to red cells over
      the entire range of flow rates investigated; however, at both high and low flow
      rate conditions, the flow field may promote activation of the clotting cascade
      due to regions of elevated shear stress adjacent to separated or stagnant flow.

PMID- 15971704
TI  - Computational modeling of the mechanical behavior of the cerebrospinal fluid
      system.
AB  - A computational fluid dynamics (CFD) model of the cerebrospinal fluid system was
      constructed based on a simplified geometry of the brain ventricles and their
      connecting pathways. The flow is driven by a prescribed sinusoidal motion of the
      third ventricle lateral walls, with all other boundaries being rigid. The
      pressure propagation between the third and lateral ventricles was examined and
      compared to data obtained from a similar geometry with a stenosed aqueduct. It
      could be shown that the pressure amplitude in the lateral ventricles increases in
      the presence of aqueduct stenosis. No difference in phase shift between the
      motion of the third ventricle walls and the pressure in the lateral ventricles
      because of the aqueduct stenosis could be observed. It is deduced that CFD can be
      used to analyze the pressure propagation and its phase shift relative to the
      ventricle wall motion. It is further deduced that only models that take into
      account the coupling between ventricles, which feature a representation of the
      original geometry that is as accurate as possible and which represent the
      ventricle boundary motion realistically, should be used to make quantitative
      statements on flow and pressure in the ventricular space.

PMID- 15971703
TI  - PIV measurements of flow in a centrifugal blood pump: time-varying flow.
AB  - Measurements of the time-varying flow in a centrifugal blood pump operating as a
      left ventricular assist device (LVAD) are presented. This includes changes in
      both the pump flow rate as a function of the left ventricle contraction and the
      interaction of the rotating impeller and fixed exit volute. When operating with a
      pulsing ventricle, the flow rate through the LVAD varies from 0-11 L/min during
      each cycle of the heartbeat. Phase-averaged measurements of mean velocity and
      some turbulence statistics within several regions of the pump, including the
      inlet, blade passage, exit volute, and diffuser, are reported at 20 phases of the
      cardiac cycle. The transient flow fields are compared to the constant flow rate
      condition that was reported previously in order to investigate the transient
      effects within the pump. It is shown that the quasi-steady assumption is a fair
      treatment of the time varying flow field in all regions of this representative
      pump, which greatly simplifies the comprehension and modeling of this flow field.
      The measurements are further interpreted to identify the effects that the
      transient nature of the flow field will have on blood damage. Although regions of
      recirculation and stagnant flow exist at some phases of the cardiac cycle, there
      is no location where flow is stagnant during the entire heartbeat.

PMID- 15971705
TI  - Determination of microvessel permeability and tissue diffusion coefficient of
      solutes by laser scanning confocal microscopy.
AB  - Interstitium contains a matrix of fibrous molecules that creates considerable
      resistance to water and solutes in series with the microvessel wall. On the basis
      of our preliminary studies, by using laser-scanning confocal microscopy and a
      theoretical model for interstitial transport, we determined both microvessel
      solute permeability (P) and solute tissue diffusion coefficient (D) of alpha
      lactalbumin (Stokes radius 2.01 nm) from the rate of tissue solute accumulation
      and the radial concentration gradient around individually perfused microvessel in
      frog mesentery. P(alpha-lactalbumin) is 1.7 +/- 0.7(SD) x 10(-6) cm/s (n = 6).
      D(t)/D(free) for alpha-lactalbumin is 27% +/- 5% (SD) (n = 6). This value of
      D(t)/D(free) is comparable to that for small solute sodium fluorescein (Stokes
      radius 0.45 nm), while p(alpha-lactalbumin) is only 3.4% of p(sodium
      fluorescein). Our results suggest that frog mesenteric tissue is much less
      selective to solutes than the microvessel wall.

PMID- 15971706
TI  - Numerical simulation for heat transfer in prostate cancer cryosurgery.
AB  - A comprehensive computational framework to simulate heat transfer during the
      freezing process in prostate cancer cryosurgery is presented. Tissues are treated
      as nonideal materials wherein phase transition occurs over a temperature range,
      thermophysical properties are temperature dependent and heating due to blood flow
      and metabolism are included. Boundary conditions were determined at the surfaces
      of the commercially available cryoprobes and urethral warmer by experimental
      study of temperature combined with a mathematical optimization process. For
      simulations, a suitable computational geometry was designed based on MRI imaging
      data of a real prostate. An enthalpy formulation-based numerical solution was
      performed for a prescribed surgical protocol to mimic a clinical freezing
      process. This computational framework allows for the individual planning of
      cryosurgical procedures and objective assessment of the effectiveness of prostate
      cryosurgery.

PMID- 15971707
TI  - A simplified procedure to determine the optimal rate of freezing biological
      systems.
AB  - The effect of several cell-level parameters on the predicted optimal cooling rate
      B(opt) of an arbitrary biological system has been studied using a well-defined
      water transport model. An extensive investigation of the water transport model
      revealed three key cell level parameters: reference permeability of the membrane
      to water L(pg), apparent activation energy E(Lp), and the ratio of the available
      surface area for water transport to the initial volume of intracellular water
      (SA/WV). We defined B(opt) as the "highest" cooling rate at which a predefined
      percent of the initial water volume is trapped inside the cell (values ranging
      from 5% to 80%) at a predefined end temperature (values ranging from -5 degrees C
      to -40 degrees C). Irrespective of the choice of the percent of initial water
      volume trapped and the end temperature, an exact and linear relationship exists
      between L(pg), SA/WV, and B(opt0. However, a nonlinear and inverse relationship
      is found between E(Lp) and B(opt). Remarkably, for a variety of biological
      systems a comparison of the published experimentally determined values of B(opt)
      agreed quite closely with numerically predicted B(opt) values when the model
      assumed 5% of initial water is trapped inside the cell at a temperature of -15
      degrees C. This close agreement between the experimental and model predicted
      optimal cooling rates is used to develop a generic optimal cooling rate chart and
      a generic optimal cooling rate equation that greatly simplifies the prediction of
      the optimal rate of freezing of biological systems.

PMID- 15971708
TI  - Functional roles of the leg muscles when pedaling in the recumbent versus the
      upright position.
AB  - An understanding of the coordination of the leg muscles in recumbent pedaling
      would be useful to the design of rehabilitative pedaling exercises. The
      objectives of this work were to (i) determine whether patterns of muscle activity
      while pedaling in the recumbent and upright positions are similar when the
      different orientation in the gravity field is considered, (ii) compare the
      functional roles of the leg muscles while pedaling in the recumbent position to
      the upright position to the upright position and (iii) determine whether leg
      muscle onset and offset timing for recumbent and upright pedaling respond
      similarly to changes in pedaling rate. To fulfill these objectives, surface
      electromyograms were recorded from 10 muscles of 15 subjects who pedaled in both
      the recumbent and upright positions at 75, 90, and 105 rpm and at a constant
      workrate of 250 W. Patterns of muscle activation were compared over the crank
      cycle. Functional roles of muscles in recumbent and upright pedaling were
      compared using the percent of integrated activation in crank cycle regions
      determined previously for upright pedaling. Muscle onset and offset timing were
      also compared. When the crank cycle was adjusted for orientation in the gravity
      field, the activation patterns for the two positions were similar. Functional
      roles of the muscles in the two positions were similar as well. In recumbent
      pedaling, the uniarticular hip and knee extensors functioned primarily to produce
      power during the extension region of the crank cycle, whereas the biarticular
      muscles crossing the hip and knee functioned to propel the leg through the
      transition regions of the crank cycle. The adaptations of the muscles to changes
      in pedaling rate were also similar for the two body positions with the
      uniarticular power producing muscles of the hip and knee advancing their activity
      to earlier in the crank cycle as the pedaling rate increased. This information on
      the functional roles of the leg muscles provides a basis by which to form
      functional groups, such as power-producing muscles and transition muscles, to aid
      in the development of rehabilitative pedaling exercises and recumbent pedaling
      simulations to further our understanding of task-dependent muscle coordination.

PMID- 15971709
TI  - Interpolating three-dimensional kinematic data using quaternion splines and
      hermite curves.
AB  - Kinematic interpolation is an important tool in biomechanics. The purpose of this
      work is to describe a method for interpolating three-dimensional kinematic data,
      minimizing error while maintaining ease of calculation. This method uses cubic
      quaternion and hermite interpolation to fill gaps between kinematic data points.
      Data sets with a small number of samples were extracted from a larger data set
      and used to validate the technique. Two additional types of interpolation were
      applied and then compared to the cubic quaternion interpolation. Displacement
      errors below 2% using the cubic quaternion method were achieved using 4% of the
      total samples, representing a decrease in error over the other algorithms.

PMID- 15971710
TI  - Musculoskeletal modeling and dynamic simulation of the thoroughbred equine
      forelimb during stance phase of the gallop.
AB  - Because thoroughbred racehorses have a high incidence of forelimb musculoskeletal
      injuries, a model was desired to screen potential risk factors for injuries. This
      paper describes the development of a musculoskeletal model of the thoroughbred
      forelimb and a dynamic simulation of the motion of the distal segments during the
      stance phase of high-speed (18 m/s) gallop. The musculoskeletal model is
      comprised of segment, joint, muscle-tendon, and ligament information. The dynamic
      simulation incorporates a proximal forward-driving force, a distal ground
      reaction force model, muscle activations, and initial positions and velocities. A
      simulation of the gallop after transection of an accessory ligament demonstrated
      increased soft tissue strains in the remaining support structures of the distal
      forelimb. These data were consistent with those previously reported from in vitro
      experimental data and supported usefulness of the model for the study of distal
      forelimb soft tissue mechanics during the stance phase of the gallop.

PMID- 15971711
TI  - Improved prediction of the collagen fiber architecture in the aortic heart valve.
AB  - Living tissues show an adaptive response to mechanical loading by changing their
      internal structure and morphology. Understanding this response is essential for
      successful tissue engineering of load-bearing structures, such as the aortic
      valve. In this study, mechanically induced remodeling of the collagen
      architecture in the aortic valve was investigated. It was hypothesized that, in
      uniaxially loaded regions, the fibers aligned with the tensile principal stretch
      direction. For biaxial loading conditions, on the other hand, it was assumed that
      the collagen fibers aligned with directions situated between the principal
      stretch directions. This hypothesis has already been applied successfully to
      study collagen remodeling in arteries. The predicted fiber architecture
      represented a branching network and resembled the macroscopically visible
      collagen bundles in the native leaflet. In addition, the complex biaxial
      mechanical behavior of the native valve could be simulated qualitatively with the
      predicted fiber directions. The results of the present model might be used to
      gain further insight into the response of tissue engineered constructs during
      mechanical conditioning.

PMID- 15971712
TI  - The Cardiocoil stent-artery interaction.
AB  - An analytical approach for the mechanical interaction of the self-expanding
      Cardiocoil stent with the stenosed artery is presented. The damage factor as the
      contact stress at the stent-artery interface is determined. The stent is
      considered as an elastic helical rod having a nonlinear pressure-displacement
      dependence, while the artery is modeled by an elastic cylindrical shell. An
      influence of a moderate relative thickness of the shell is estimated. The
      equations for both the stent and the artery are presented in the stent-associated
      helical coordinates. The computational efficiency of the model enabled to carry
      out a parametric study of the damage factor. Comparative examinations are
      conducted for the stents made of the helical rods with circular and rectangular
      cross sections. It was found, in particular, that, under same other conditions,
      the damage factor for the stent with a circular cross section may be two times
      larger than that for a rectangular one.

PMID- 15971713
TI  - The role of fiber-matrix interactions in a nonlinear fiber-reinforced strain
      energy model of tendon.
AB  - The objective of this study was to develop a nonlinear and anisotropic three
      dimensional mathematical model of tendon behavior in which the structural
      components of fibers, matrix, and fiber-matrix interactions are explicitly
      incorporated and to use this model to infer the contributions of these structures
      to tendon mechanical behavior. We hypothesized that this model would show that:
      (i) tendon mechanical behavior is not solely governed by the isotropic matrix and
      fiber stretch, but is also influenced by fiber-matrix interactions; and (ii)
      shear fiber-matrix interaction terms will better describe tendon mechanical
      behavior than bulk fiber-matrix interaction terms. Model versions that did and
      did not include fiber-matrix interaction terms were applied to experimental
      tendon stress-strain data in longitudinal and transverse orientations, and the R2
      goodness-of-fit was evaluated. This study showed that models that included fiber
      matrix interaction terms improved the fit to longitudinal data (R2(toe) = 0.88,
      R2(Lin) = 0.94) over models that only included isotropic matrix and fiber stretch
      terms (R2(Toe) = 0.36, R2(Lin) = 0.84). Shear fiber-matrix interaction terms
      proved to be responsible for the best fit to data and to contribute to stress
      strain nonlinearity. The mathematical model of tendon behavior developed in this
      study showed that fiber-matrix interactions are an important contributor to
      tendon behavior The more complete characterization of mechanical behavior
      afforded by this mathematical model can lead to an improved understanding of
      structure-function relationships in soft tissues and, ultimately, to the
      development of tissue-engineered therapies for injury or degeneration.

PMID- 15971714
TI  - Shape memory alloy clip for compression colonic anastomosis.
AB  - This study was setup to investigate the design and performance of a shape memory
      alloy clip for colonic anastomosis. The thermo-mechanical properties of the shape
      memory alloy material were studied and the data were used to derive a nonlinear
      material model. This enabled the development of computer computer aided design
      models and finite element analysis of the clip and tissue compression. The
      maximum strain of the anastomosis clip was within the recoverable range, and it
      exerted parallel compression of the colonic walls with a uniform pressure
      distribution. The design of the anastomosis clip was optimized for safe, simple,
      and effective use in colon surgery.

PMID- 15971715
TI  - A new litigation cost: losing the mentor base--guest editorial.

PMID- 15971716
TI  - Female urinary incontinence: what the epidemiologic data tell us.
AB  - The prevalence of urinary incontinence (UI) in women has been the subject of many
      epidemiologic studies. Since 1968 the field has accumulated sufficient data that
      we now know how stress UI and urge UI appear in populations categorized by race,
      age, parity, body mass index and other demographic factors. The first
      comprehensive study in the U.S., the MESA study, was done in 1983. For community
      dwelling women 60 years or older, it came up with the now familiar figure of 38%
      in this age-group. Very similar figures have been found in other national
      populations, but there are great differences in sub-populations and also by type-
      stress, urge, or mixed UI. However, with all differences in prevalence
      acknowledged, no type of UI is unusual in a population of older women. This
      article delineates, with detailed discussion of individual studies, prevalence by
      type, age, race, obstetric and gynecologic-surgery history, and anatomic
      dysfunction, plus consideration of the effects of obesity and menopause on UI.
      The conclusion is that a problem so widespread is a candidate for prevention, and
      that the few trials in this direction should be augmented.

PMID- 15971717
TI  - Advances in urogynecology.
AB  - Pelvic floor disorders include urinary incontinence, pelvic organ prolapse, and
      bowel dysfunction, all of which can cause considerable disability and anxiety.
      One third of all women will suffer from these disorders at some point in their
      life. All are often embarrassing and may act as barriers to healthy living as
      many women suffer in silence. The field of urogynecology has evolved over time to
      meet the needs of women who struggle with disorders of the pelvic floor. An
      increase in the awareness and treatment of these disorders has led to improved
      scientific research in the form of prospective randomized clinical trials to
      develop a unified understanding of their epidemiology, biology, and treatment.
      This review explores the literature that has promoted advances in the
      understanding of pelvic floor disorders and discusses some of the new technology
      and research that is being done in the field.

PMID- 15971718
TI  - Stress incontinence: alternatives to surgery.
AB  - Although surgery is commonly performed to alleviate or cure stress incontinence,
      there are non-surgical options that might well be explored and tried before a
      woman undergoes surgery, for which many are poor candidates. The least drastic
      treatments are behavioral therapies, chiefly pelvic floor muscle training (Kegel
      exercises), alone or with biofeedback. This method is effective but has the
      drawback of poor patient compliance. Another therapy, almost noninvasive, is
      electrical stimulation via needle or surface electrodes of the pudendal nerve and
      the pelvic plexus in order to treat detrusor instability. Some studies show good
      results for many patients; and there is no need for long-term compliance. Medical
      management has included hormone replacement therapy and alpha-adrenergic
      agonists, but questionable results and intolerable risks have shifted this mode
      to serotonin-norepinephrine reuptake inhibitors, which have CNS action. Finally,
      there are urethral occlusive devices, which have poor acceptance owing to side
      effects and difficulty of use, and vaginal pessaries, theoretically attractive
      but inexplicably poor performers in the marketplace.

PMID- 15971719
TI  - The overactive bladder and quality of life.
AB  - Overactive bladder (OAB) affects 16.6% of the U.S. population, or 33 million
      adults, in some form. Despite the prevalence of OAB, almost 60% of those affected
      seek no medical assistance for the condition either because of embarrassment or
      the misconception that it represents an inevitable function of aging. A recent
      surge of interest on the subject has uncovered the dramatic effect that OAB can
      have on social interactions, sleep, depression, sexual health, and overall health
      related quality of life (HRQoL). The introduction of validated, condition
      specific QOL questionnaires has enhanced our ability to measure these subjective
      dimensions of OAB, and to assess their response to therapeutic interventions.

PMID- 15971720
TI  - Overactive bladder: treatment options for the aging woman.
AB  - Overactive bladder (OAB) is a common, chronic, and debilitating condition that is
      most often observed in the elderly population. It has a profound impact on the
      quality of life of patients, affecting many aspects of daily living, social
      interaction, and self-perception of health status. Possible neurological,
      muscular, and metabolic causes have been proposed, but in most cases the exact
      pathophysiology remains unclear. The management of OAB can be initiated
      conservatively with behavioral modification and antimuscarinics. For refractory
      cases, neuromodulation, denervation techniques, and bladder augmentation may be
      indicated. Not all patients are cured, but most may be improved with appropriate
      individualized therapy.

PMID- 15971721
TI  - 'Baby talk' attracts neighbors to new Manassas, Va., birthing center.
AB  - An dollar 80 million expansion plan recently was launched by Prince William
      Hospital, Manassas, Va. The cornerstone of the plan is the new Hylton Family
      Birthing Center. The hospital employed a full range of tactics to promote the
      opening of the birthing center. These ranged from quarterly newsletters to
      billboards; from tours and radio spots to a newly revised web site. The campaign
      is characterized by infant testimonials, gentle humor and bright colors.

PMID- 15971723
TI  - Medical City introduces new magazine for Dallas community.
AB  - Medical City, Dallas, launches a quarterly magazine titled, IN: Mind Body Life,
      as the final phase in its two-year branding campaign. In search of a unique
      style, the hospital worked with American Airlines' publishing house, AAP Custom.

PMID- 15971724
TI  - Profile in community cooperation: Delaware big in fighting cancer.
AB  - The Delaware Cancer Treatment Program, created under an official state mandate,
      provides support for Delawareans diagnosed with any cancer who are without health
      insurance and who are ineligible for Medicaid.The multi-faceted campaign shown
      here includes information kits designed to help community leaders as they
      encourage men to be screened for prostate cancer. Also, it directly enlists
      physicians in this effort.

PMID- 15971726
TI  - Web site offers evidence hospital is county's most preferred hospital.
AB  - We review the recently-renovated web site for Bridgeport Hospital, Bridgeport,
      Conn., or "Fairfield County's Most Preferred Hospital." The site,
      www.bridgeporthospital.com, offers a wide-ranging selection of links to afford
      its readers plentiful information about its various specialties, special events,
      and available physicians.

PMID- 15971727
TI  - Howard University Hospital finds partner in helping children succeed.
AB  - Howard University Hospital, Washington, D.C., becomes the site for the launch of
      a national ad campaign by the nonprofit youth education organization, Communities
      in Schools. The hospital and university share the organization's mission of
      supporting young people in the community.

PMID- 15971728
TI  - Aspens convey Grinnell's message.
AB  - Grinnell Regional Medical Center, Grinnell, Iowa, used the theme of an aspen
      grove for its 2002 annual report. It met the challenge of producing and mailing
      the usual number of copies while reducing the budget. The effort succeeded by
      eliminating color print, reducing the number of pages and mailing to "occupants"
      in its region, instead of designating them by name.

PMID- 15971729
TI  - Thought about annual reports.
AB  - Editor Tom Rees shares the observations of other experts on the subject of
      creating your annual report.

PMID- 15971730
TI  - Iron deficiency anemia in adolescence.

PMID- 15971731
TI  - Oral health practices among adolescents: a study from family practice clinics in
      Israel.
AB  - Dental caries and periodontal disease are highly prevalent among adolescents.
      Preventive dental visits and proper oral health practices effectively reduce the
      occurrence of these entities. The objective of this study was to determine the
      rates of tooth brushing, flossing, and visits to dentists and hygienists among
      Israeli adolescents in a family practice setting. One hundred and eighty-four 7th
      and 10th graders who attended preventive health visits completed questionnaires
      that included questions regarding dental visits and personal oral health habits.
      Structured counseling by the family nurse was provided following completion of
      the questionnaire. Ninety-seven percent of the teenagers brushed their teeth at
      least once a day, but only 7% used dental floss daily, 44.5% never flossed, and
      another 10% didn't know what dental floss was. Eighty-three percent had visited a
      dentist, but only 33% had been to a dental hygienist in the past two years.
      Twenty-nine percent did not know what a hygienist was. We conclude that primary
      care providers can promote oral health by screening and providing counseling to
      their adolescent patients.

PMID- 15971732
TI  - Meaning of family reunification as interpreted by young Chinese immigrants.
AB  - This paper is a narrative analysis of young Chinese immigrants' subjective
      interpretation of their family reunification in Hong Kong. The major objectives
      of the study were to understand what family reunification actually meant to them
      and how it affected their subsequent adjustment. It also tried to examine the
      similarities and differences in the experience and interpretation of family
      reunification among young immigrants who had different levels of adjustment.
      Participants in this study included 45 immigrants, aged between 12 and 17.
      Research findings show that family reunification was their long-cherished wish
      and the main reason for their migration. It was not only their primary concern
      before coming to Hong Kong but also the stance from which separation with close
      relatives in their native place and the subsequent hardships as a new comer in
      the competitive host society were justified. Reunification of the family and
      harmonious and caring relationship among family members had been the source of
      comfort and support for those who had successful adjustment. However, for those
      who did not experience warmth and concern from family members, the
      disillusionment with a happy family reunification and the experience of distant
      or even conflictive family relationship had not only created in them a sense of
      alienation but also resulted in poor adjustment in the new environment.

PMID- 15971733
TI  - Self-perception of body weight among high school students in Taipei, Taiwan.
AB  - Self-perception of body weight and other weight-related factors were assessed
      among 2665 Taipei, Taiwan high school students. A high percent of the girls
      (70.7%) and boys (42.2%) reported that they were too fat and these percentages
      were much higher than those reported by U.S. students in a recent Youth Risk
      Behavior Survey. In addition, only 13.2% of girls and 22.0% of boys reported
      being completely satisfied with their weight and the level of dissatisfaction
      with weight appeared to be greater than among U.S. students. Yet, in comparison
      to U.S. students, the Taiwanese students were considerably less likely than their
      U.S. counterparts to engage in weight management practices (e.g., dieting, eating
      less food, using diet pills). Taiwanese students with a self-perception of being
      too fat were more likely than those with perceptions of being just right or too
      thin to engage in weight management practices, to be dissatisfied with their
      weight, feel that they were unattractive, estimate that their same-sex peers were
      trying to lose weight, and have a higher body mass index. The findings from this
      study showed a relationship between self-perception of body size and engaging in
      weight control behaviors was consistent with other research. It suggested that
      self-perception of body weight, more so than objective weight status, was
      predictive of weight loss behavior and also negative psychological outcomes
      associated with poor body weight image. As a result, self-perception of weight
      may be an important point of focus for the design and implementation of clinical
      and public health initiatives targeted at this adolescent population as well as
      others.

PMID- 15971734
TI  - Teenage smoking: a longitudinal analysis.
AB  - This paper examines the binary recurrent outcome "teenage smoking" within a
      statistical modelling paradigm. The proposed statistical modelling relates
      smoking to a set of explanatory variables, which include subjective as well as
      objective measures. In order to assess the degree to which explanatory variables
      influence smoking, an adequate statistical model must handle the possibility that
      substantial variation between respondents will be due to omitted variables,
      multicollinearity and past behaviour. An earlier paper, using a secondary cross
      sectional data source, concluded that an investigation of smoking needs to be
      based on longitudinal data using appropriate statistical modelling. The same data
      source provided observations on young adults over a period of 2 years. For
      comparison purposes, the same cross-sectional model was fitted to the
      longitudinal data. The results suggest there may be substantial heterogeneity due
      to omitted variables in the data and complex inter-relationships between observed
      explanatory variables leading to underestimation. Longitudinal data provide
      additional flexibility to control for omitted variables and are necessary to
      investigate dynamic social processes such as smoking. The results from our
      analysis suggest that the effects of variables reported in the literature on
      teenage smoking may be overestimated. For example, the role of peer pressure may
      not be as clear as it has been made out to be.

PMID- 15971735
TI  - Adolescent Chinese immigrants in Hong Kong: a comparison with locally born
      students and factors associated with their psychological well-being.
AB  - The present research aims to compare the psychological well-being of young
      Mainland Chinese immigrants and locally born students in Hong Kong and to
      identify factors that are associated with the psychological well-being of young
      immigrants. Participants, aged from 12 to 17 years, included 1,109 youngsters
      born in Hong Kong and 342 new immigrants from Mainland China. Factors examined in
      this research included individual demographic and socio-economic factors like
      age, gender, length of residence in the host society and the financial situation
      of immigrants' immediate family, as well as personal factors including
      immigrants' self-concept, perceived discrimination, and educational aspiration.
      Findings indicated that the psychological well-being of young Mainland Chinese
      immigrants was on the whole better than that of the locally born students.
      Findings also revealed that demographic factors did not have significant
      correlation with the psychological functioning of young immigrants, while
      personal factors generally correlated significantly with their psychological well
      being.

PMID- 15971736
TI  - Multi-site study of transition in adolescents with sickle cell disease in the
      United Kingdom and the United States.
AB  - Adolescents with sickle cell disease may have problems of adjustment during the
      phase of transition from pediatric to adult health care. It is important to
      identify factors that may help in the development of appropriate interventions.
      We were interested in possible similarities, in terms of adjustment to transition
      in two countries where health service provision is quite different. The study
      employed a cross-sectional survey design, with a sample of adolescents (still in
      pediatric care) drawn from a U.S.A national sample and a single U.K. site. A
      battery of validated disease-specific measures was used to assess adolescent
      perceptions of physical and psychological symptoms, self-efficacy, self
      management skills, and gather demographic data. There were no significant
      demographic differences between the samples of adolescents in the two countries.
      Taken together, the two populations indicate that adolescent age and educational
      level were associated with symptoms (physical and psychological). Self-efficacy
      is not associated with demographic factors, but is predicted by physical
      symptoms, while different aspects of self-management are predicted by age
      (responsibility with care), educational level (independence and confidence with
      care) and psychological symptoms (knowledge about SCD and confidence with care).
      This study highlights the importance of gathering disease-specific transitional
      information from adolescents with sickle cell disease in the U.K. and U.S.A. It
      also shows that demographic variables have to be considered in the development of
      any intervention programme.

PMID- 15971737
TI  - Iron deficiency anemia in a group of Turkish adolescents: frequency and
      contributing factors.
AB  - Need for iron increases rapidly during adolescence. In girls, this is primarily
      due to the beginning of menstruation and dieting to loose weight, while in boys
      increased erythropoetic activity during pubertal period is the major cause.
      Between November 1999 and June 2000, 2,900 patients, between 9-17 years of age
      were screened for the presence of anemia in our Adolescent Outpatient Clinic.
      Tanner's scale of sexual maturation was used to categorize genital development.
      Those patients diagnosed with anemia were further examined for bone age, history
      of pica, parasitosis and gastrointestinal symptoms. Complete blood count showed
      anemia in 44 patients. Twenty one patients (15 girls and 6 boys) were diagnosed
      with iron deficiency anemia, 19 (15 girls and 4 boys) were diagnosed with anemia
      associated with infections, 3 (two girls and one boy) were carriers for beta
      thalasemia and one girl had acute myeloblastic leukemia. Laboratory parameters
      alone were not enough in the diagnosis of iron deficiency, but age, sex, growth
      rate and sexual maturation stage in the pubertal period must be taken into
      consideration. We suggest that the reason for the lower rate of iron deficiency
      anemia in our patients, than expected for this age group, could be due to our
      patient population being more aware and careful about a balanced diet compared to
      the feeding behaviour of the general population in Turkey. Further studies that
      include lower socio-economic groups are necessary to conclude the prevalance of
      iron deficiency anemia among adolescents.

PMID- 15971738
TI  - Aripiprazole for agitation in a 13-year-old girl with neuroleptic malignant
      syndrome.
AB  - Neuroleptic Malignant Syndrome (NMS) rarely results from atypical antipsychotic
      therapy. To date, no information is available on the incidence of NMS with
      aripiprazole, a newer neuroleptic. OBJECTIVE: To examine the results of a trial
      of aripiprazole administered to a 13-year-old Mexican-American girl during the
      course of NMS. METHODS: Vital signs and laboratory values obtained before and
      during the aripiprazole trial were compared. RESULTS: Aripiprazole administration
      resulted in a mild increase in tachycardia and brief worsening of serum
      creatinine kinase level, but did not significantly affect temperature,
      respiratory rate, or blood pressure. CONCLUSIONS: In this adolescent with NMS,
      aripiprazole treatment was associated with a mild worsening of symptoms.

PMID- 15971739
TI  - Recent trends in adolescent asthma.
AB  - Asthma is a disability that can affect the quality of life of the adolescent
      going through a period with difficulty and often rebellion, but gentle care from
      the primary physician will guide the adolescent through this period. A worldwide
      increase in childhood asthma has been observed and recent data from the National
      Health Interview Survey-2003 in the United States showed an overall 12.5% of
      children under age 18 years, who ever had asthma diagnosed. This short
      communication reviews the recent U.S. findings with research on adolescent asthma
      in Israel, where a study from year 2000 found a higher percentage of ever had
      diagnosed asthma (13.7%).

PMID- 15971740
TI  - Consortium of otolaryngology-head and neck surgery journals to collaborate in
      maintenance of high ethical standards.

PMID- 15971741
TI  - Cholesterol granuloma.

PMID- 15971742
TI  - Septal perforation caused by nasal magnetic foreign bodies.

PMID- 15971743
TI  - Acute ulcerative laryngitis.

PMID- 15971744
TI  - Unusual rhinosinusitis caused by Curvularia fungi.

PMID- 15971745
TI  - Metastatic cystic squamous cell carcinoma.

PMID- 15971746
TI  - Pleomorphic adenoma of the accessory parotid gland.

PMID- 15971747
TI  - Repair of enlarged pierced-ear openings.

PMID- 15971748
TI  - Prompt reimbursement: tracking accounts receivable by carrier type.

PMID- 15971749
TI  - A means of achieving more surgical exposure during transoral surgery on the
      tongue base and vallecula.

PMID- 15971750
TI  - Auditory steady-state response audiometry in profound SNHL: the impact of
      abnormal middle ear function.
AB  - Auditory steady-state response (ASSR) audiometry is a commercially available tool
      that is used to predict behavioral auditory threshold levels. Its particular
      value stems from the technology's ability to measure frequency-specific responses
      in the background electroencephalogram to auditory stimuli presented across a
      broad range of frequencies and sound pressure levels. It is clearly of benefit
      when used to assess threshold levels in infants and children with severe-to
      profound hearing impairment (i.e., cochlear implant candidates). Although
      numerous authors have provided evidence of the usefulness of ASSR testing, their
      reports have concerned patients whose middle ear impedance measures were normal.
      We report the cases of 2 patients who, following improvement of abnormal middle
      ear impedance values, experienced a marked improvement in measurable thresholds
      by ASSR testing.

PMID- 15971751
TI  - Use of a powered shaver to remove multiple oral cavity papillomas.
AB  - We report a previously undescribed method of removing multiple oral papillomas,
      which we performed on 5 men with human immunodeficiency virus (HIV) infection.
      Patients were brought to the operating room and placed under general anesthesia.
      In addition, 1% lidocaine with 1:100,000 epinephrine was injected under and
      around the lesions. We then removed the lesions with a Tricut laryngeal blade
      attached to a handheld powered shaver Postoperatively, patients were sent home on
      clindamycin, a pain medication, and Peridex. At the 1-week follow-up, patients
      reported only minimal pain, and their wounds were well healed. We observed no
      adverse events associated with the shaving procedure. Our method expedites the
      process of removing multiple oral cavity papillomas while reducing the morbidity
      generally associated with other procedures.

PMID- 15971752
TI  - Endoscopic ligation of the sphenopalatine artery as a primary management of
      severe posterior epistaxis in patients with coagulopathy.
AB  - We describe our experience with endoscopic ligation of the sphenopalatine artery
      in the treatment of severe posterior epistaxis in 2 patients with coagulopathy.
      Conservative treatment had failed in both cases. The key elements of this
      procedure are the identification of the branches of the sphenopalatine artery via
      an endoscopic endonasal approach and the application of two titanium clips under
      direct vision. This procedure was successful in both patients, and we recommend
      it in selected cases.

PMID- 15971753
TI  - Pneumomediastinum, an unusual complication of facial trauma.
AB  - Pneumomediastinum is often an incidental finding following a blunt or penetrating
      trauma to the neck or chest. We report a rare case of pneumomediastinum following
      an isolated facial trauma that was diagnosed on imaging. We also review the
      clinical signs of this condition, its radiologic characteristics, and the 18
      previously reported cases of pneumomediastinum following facial trauma.

PMID- 15971754
TI  - Biphasic synovial sarcoma of the posterior pharyngeal wall: a case report.
AB  - Synovial sarcoma is not common in the head and neck region. Because its
      histopathologic features are many and varied, it is often misdiagnosed. We report
      a case of biphasic synovial sarcoma of the posterior pharyngeal wall, and we
      discuss the clinical and pathologic features of this case.

PMID- 15971755
TI  - Minimally invasive surgery for parotid pleomorphic adenoma.
AB  - Compared with total parotidectomy and complete superficial parotidectomy for the
      removal of a parotid pleomorphic adenoma, partial superficial parotidectomy with
      dissection and preservation of the facial nerve--defined as the excision of a
      tumor with a 2-cm margin of normal parotid parenchyma except at the point where
      the tumor abuts the facial nerve--is associated with a lower incidence of
      transient facial nerve dysfunction, facial contour disfigurement, and subsequent
      Frey's syndrome. The partial procedure is not associated with any increase in
      recurrence, and it requires less operating time. The author hypothesized that the
      use of this procedure to remove a benign pleomorphic adenoma might result in even
      less morbidity (transient or permanent facial nerve dysfunction, facial contour
      disfigurement, Frey's syndrome, and hypoesthesia) without increasing the risk of
      recurrence if only a 1-cm margin of normal parotid parenchyma was removed and if
      the posterior branches of the great auricular nerve were preserved To test this
      hypothesis, the author conducted a retrospective study of 30 patients--15 who had
      undergone the standard partial procedure (2-cm margin with great auricular nerve
      sacrifice) and 15 who had undergone the modified version (1-cm margin with great
      auricular nerve preservation). After a mean follow-up of 10 years, there were no
      significant differences between the two groups in terms of facial nerve
      dysfunction, facial contour disfigurement, Frey's syndrome, and recurrence.
      Moreover, preservation of the posterior branches of the great auricular nerve did
      not prevent alterations in sensitivity (i.e., hypoesthesia) in 7 of the 15
      patients (46.7%). Although a 1-cm area of normal parotid parenchyma around a
      benign pleomorphic adenoma was a safe margin, it was no better than a 2-cm margin
      in terms ofmorbidity and recurrence. Preservation of the posterior branches of
      the great auricular nerve will result in an objective reduction in hypoesthesia
      in approximately half of patients, but because it does not ensure freedom from
      sensitivity alterations in all cases, patients should be advised of the risk of
      postoperative numbness in the earlobe and the infraauricular area.

PMID- 15971756
TI  - The carotid-vertebral space: an 'extended' lateral window to the ventromedial
      cranial base and lower craniocervical junction.
AB  - We describe a unique method of accessing the ventromedial skull base and lower
      craniocervical junction. Our method employs a trajectory between that of the more
      anterior transoral or retropharyngeal approaches and the various posterior or
      posterolateral skull base approaches. This "extended" lateral approach allows
      surgeons to resect very large tumors of the skull base through a single incision.
      The operative field is more extensive than that achieved with other approaches;
      it extends from the cerebellar hemisphere to the extradural ventral upper
      cervical spine, and it provides access to tissue outside the spinal canal, such
      as the ventral strap muscles. We describe our use of this approach during a
      single-stage resection of a large hemangiopericytoma in a 37-year-old man.

PMID- 15971757
TI  - Expanding the concept of unresolved mental states: hostile/helpless states of
      mind on the Adult Attachment Interview are associated with disrupted mother
      infant communication and infant disorganization.
AB  - In a recent meta-analysis, only 53% of disorganized infants were predicted by
      parental Unresolved states of mind on the Adult Attachment Interview (AAI). The
      goal of this study was to identify additional predictors of infant
      disorganization on the AAI by developing and validating an interview-wide coding
      system for Hostile/Helpless (H/H) parental states of mind with respect to
      attachment. Maternal AAls were collected from 45 low-income mothers with high
      rates of childhood trauma when their children were age 7; Strange Situation
      assessments had been collected at 18 months of age. AAIs were independently coded
      using both the Main and Goldwyn coding system and newly developed codes for H/H
      states of mind. Results indicated that the H/H coding system displayed
      discriminant validity in that it did not overlap substantially with the
      Unresolved, Cannot Classify, or Fearfully Preoccupied by Traumatic Events
      categories in the Main and Goldwyn coding system. Second, H/H states of mind
      accounted for variance in disorganized infant behavior not associated with the
      Unresolved classification. Third, H/H states of mind were significantly related
      to maternal disrupted affective communication as coded by the Atypical Maternal
      Behavior Instrument for Assessment and Classification coding system, and maternal
      disrupted communication mediated the relations between H/H states of mind and
      infant disorganization.

PMID- 15971758
TI  - Developmental foundations of externalizing problems in young children: the role
      of effortful control.
AB  - Examined associations between effortful control temperament and externalizing
      problems in 220 3-year-old boys and girls, controlling for co-occurring cognitive
      and social risk factors. We also considered possible additive and/or interactive
      contributions of child dispositional anger and psychosocial adversity, and
      whether relations between effortful control and early externalizing problems were
      moderated by child gender. Individual differences in children's effortful control
      abilities, assessed using behavioral and parent rating measures, were negatively
      associated with child externalizing problems reported by mothers, fathers, and
      preschool teachers. These associations were not overshadowed by other cognitive
      or social risk factors, or by other relevant child temperament traits such as
      proneness to irritability. Further analyses revealed that associations between
      externalizing problem behavior and effortful control were specific to components
      of child problem behavior indexing impulsive-inattentive symptoms. Thus,
      children's effortful control skills were important correlates of children's early
      disruptive behavior, a finding that may provide insight into the developmental
      origins of chronic behavioral maladjustment.

PMID- 15971759
TI  - Emotion understanding and theory of mind among maltreated children in foster
      care: evidence of deficits.
AB  - Children in foster care are at heightened risk for poor psychosocial outcomes.
      This study examined differences in two areas that may be associated with many of
      these outcomes, emotion understanding and theory of mind, using a sample of 3- to
      5-year-old maltreated foster children (n = 60) and a comparison group of same
      aged, low-income, nonmaltreated children living with their biological families (n
      = 31). Being in foster care was significantly associated with worse emotion
      understanding and theory of mind capabilities, even when accounting for age,
      intelligence, and executive function. There were no significant associations
      between length of time in foster care, number of transitions, and emotion
      understanding and theory of mind. Results help to expand knowledge about the
      cognitive and affective deficits of children in foster care and suggest that
      interventions targeted at these deficits include an emphasis on emotion
      understanding and theory of mind.

PMID- 15971761
TI  - Low positive emotionality in young children: association with EEG asymmetry.
AB  - Low positive emotionality (PE; e.g., listlessness, anhedonia, and lack of
      enthusiasm) has been hypothesized to be a temperamental precursor or risk factor
      for depression. The present study sought to evaluate the validity of this
      hypothesis by testing whether low PE children have similar external correlates as
      individuals with depression. This paper focused on the external correlate of EEG
      asymmetry. Previous studies have reported that individuals at risk for depression
      exhibited a frontal EEG asymmetry (greater right than left activity). Others have
      reported an association with posterior asymmetries (greater left than right
      activity). In the present study, children classified as having low PE at age 3
      exhibited an overall asymmetry at age 5-6 with less relative activity in the
      right hemisphere. This asymmetry appeared to be largely due to a difference in
      the posterior region because children with low PE exhibited decreased right
      posterior activity whereas high PE children exhibited no posterior asymmetry.
      These findings support the construct validity of the hypothesis that low PE may
      be a temperamental precursor or risk factor for depression.

PMID- 15971760
TI  - Nature X nurture: genetic vulnerabilities interact with physical maltreatment to
      promote conduct problems.
AB  - Maltreatment places children at risk for psychiatric morbidity, especially
      conduct problems. However, not all maltreated children develop conduct problems.
      We tested whether the effect of physical maltreatment on risk for conduct
      problems was strongest among those who were at high genetic risk for these
      problems using data from the E-risk Study, a representative cohort of 1,116 5
      year-old British twin pairs and their families. Children's conduct problems were
      ascertained via parent and teacher interviews. Physical maltreatment was
      ascertained via parent report. Children's genetic risk for conduct problems was
      estimated as a function of their co-twin's conduct disorder status and the pair's
      zygosity. The effect of maltreatment on risk for conduct problems was strongest
      among those at high genetic risk. The experience of maltreatment was associated
      with an increase of 2% in the probability of a conduct disorder diagnosis among
      children at low genetic risk for conduct disorder but an increase of 24% among
      children at high genetic risk. Prediction of behavioral pathology can attain
      greater accuracy if both pathogenic environments and genetic risk are
      ascertained. Certain genotypes may promote resistance to trauma. Physically
      maltreated children whose first-degree relatives engage in antisocial behavior
      warrant priority for therapeutic intervention.

PMID- 15971762
TI  - Inattention/hyperactivity and aggression from early childhood to adolescence:
      heterogeneity of trajectories and differential influence of family environment
      characteristics.
AB  - Inattention/hyperactivity and aggressive behavior problems were measured in 335
      children from school entry throughout adolescence, at 3-year intervals. Children
      were participants in a high-risk prospective study of substance use disorders and
      comorbid problems. A parallel process latent growth model found aggressive
      behavior decreasing throughout childhood and adolescence, whereas
      inattentive/hyperactive behavior levels were constant. Growth mixture modeling,
      in which developmental trajectories are statistically classified, found two
      classes for inattention/hyperactivity and two for aggressive behavior, resulting
      in a total of four trajectory classes. Different influences of the family
      environment predicted development of the two types of behavior problems when the
      other behavior problem was held constant. Lower emotional support and lower
      intellectual stimulation by the parents in early childhood predicted membership
      in the high problem class of inattention/hyperactivity when the trajectory of
      aggression was held constant. Conversely, conflict and lack of cohesiveness in
      the family environment predicted membership in a worse developmental trajectory
      of aggressive behavior when the inattention/hyperactivity trajectories were held
      constant. The implications of these findings for the development of
      inattention/hyperactivity and for the development of risk for the emergence of
      substance use disorders are discussed.

PMID- 15971763
TI  - Peer relationship antecedents of delinquent behavior in late adolescence: is
      there evidence of demographic group differences in developmental processes?
AB  - A longitudinal prospective design was used to test the generalizability of low
      levels of social preference and high levels of antisocial peer involvement as
      risk factors for delinquent behavior problems to African American (AA) and
      European American (EA) boys and girls (N = 384). Social preference scores were
      computed from peer reports in middle childhood (ages 6-9). Parents and
      adolescents reported antisocial peer involvement in early adolescence (ages 13
      16) and adolescents reported on their own delinquent behavior in late adolescence
      (ages 17 and 18). Analyses tested for differences across four groups (AA boys, EA
      boys, AA girls, EA girls) in construct measurement, mean levels, and associations
      among variables. Few measurement differences were found. Mean-level differences
      were found for social preference and delinquent behavior. AA boys were least
      accepted by peers and reported the highest level of delinquent behavior. EA girls
      were most accepted by peers and reported the lowest level of delinquent behavior.
      Associations among peer experiences and delinquent behavior were equivalent
      across groups, with lower levels of social preference and higher levels of
      antisocial peer involvement associated with more delinquent behavior. Person
      centered analyses showed the risk associated with low social preference and high
      antisocial peer involvement to be similar across groups, providing further
      evidence of the generalizability of the peer relationship experiences as risk
      factors for subsequent delinquent behavior problems.

PMID- 15971765
TI  - Low salivary cortisol levels and externalizing behavior problems in youth.
AB  - Research linking basal cortisol levels with internalizing and externalizing
      behavior problems in youths has yielded inconsistent results. We hypothesize that
      the high moment to moment variation in adrenocortical activity requires an
      analytical strategy that separates variance in cortisol levels attributable to
      "stable traitlike" versus "state or situationally specific" sources. Early
      morning saliva samples were obtained from 724 youths (M age = 13.5 years; range =
      6-16 years in Year 1) on 2 successive days 1 year apart. Latent state-trait
      modeling revealed that 70% of the variance in cortisol levels could be attributed
      to statelike sources, and 28% to traitlike sources. For boys only, higher levels
      of externalizing problem behaviors were consistently associated with lower
      cortisol attributable to traitlike sources across 3 years of behavioral
      assessment. The inverse association between individual differences in cortisol
      and externalizing problem behavior has previously only been reported in studies
      of at-risk or clinical groups. The present findings suggest the relationship is a
      stable phenomenon that spans both normative and atypical child development.
      Studies are needed to reveal the biosocial mechanisms involved in the
      establishment and maintenance of this phenomenon, and to decipher whether
      individual differences in this hormone-behavior link confers risk or resilience.

PMID- 15971764
TI  - How are parent-child conflict and childhood externalizing symptoms related over
      time? Results from a genetically informative cross-lagged study.
AB  - The present study attempted to determine the direction and etiology of the robust
      relationship between childhood externalizing (EXT) symptoms and parent-child
      conflict using a genetically informative longitudinal model and data from the
      ongoing Minnesota Twin Family Study. Participants consisted of 1,506 same-sex
      twins assessed at ages 11 and 14, and their parents. The relationship between EXT
      and parent-child conflict from ages 11 to 14 was examined within a biometrical
      cross-lagged design. The results revealed three primary findings: first, the
      stability of conflict and externalizing over time is largely, although not
      solely, a result of genetic factors. Second, there appears to be a bidirectional
      relationship between conflict and EXT over time, such that both conflict and EXT
      at 11 independently predict the other 3 years later. Finally, the results are
      consistent with the notion that parent-child conflict partially results from
      parental responses to their child's heritable externalizing behavior, while
      simultaneously contributing to child externalizing via environmental mechanisms.
      These results suggest a "downward spiral" of interplay between parent-child
      conflict and EXT, and offer confirmation of a (partially) environmentally
      mediated effect of parenting on child behavior.

PMID- 15971766
TI  - Longitudinal links among parenting, self-presentations to peers, and the
      development of externalizing and internalizing symptoms in African American
      siblings.
AB  - A longitudinal model that linked involved-supportive parenting and siblings'
      ability-camouflaging self-presentations to peers with the development of
      externalizing and internalizing symptoms was tested with 152 pairs of first- and
      second-born African American siblings (mean ages 12.7 years and 10.2 years at the
      first wave of data collection). Three waves of data were collected at 1-year
      intervals. Teachers assessed siblings' externalizing symptoms, internalizing
      symptoms, and academic competence; siblings reported their own self-presentations
      and desire for peer acceptance; and mothers and siblings provided multiinformant
      assessments of involved-supportive parenting. Involved-supportive parenting at
      Wave 1 was linked with peer-directed self-presentations at Wave 2. Wave 2 self
      presentations were linked indirectly with changes from Wave 1 to Wave 3 in
      externalizing and internalizing symptoms through their association with academic
      competence.

PMID- 15971767
TI  - Comparable "risks" at the socioeconomic status extremes: preadolescents'
      perceptions of parenting.
AB  - This study was focused on contextual variations in the parenting dimensions
      salient for preadolescent adjustment. The sample consisted of 614 sixth graders
      from two communities, one low and the other high income. Parenting dimensions
      included those known to be significant in each socioeconomic context: isolation
      from parents (emotional and physical), and parents' emphasis on achievements
      (overall expectations and emphasis on integrity over success). Adjustment
      outcomes included subjective well-being as well as school competence.
      Contradicting stereotypes, results showed that on average, very affluent children
      can perceive their parents as emotionally and physically unavailable to the same
      degree that youth in serious poverty do. The ramifications for adjustment also
      seem to be largely similar: Closeness to parents was beneficial for all, just as
      criticism was deleterious. Even after considering the quality of parent-child
      relationships, parents' physical absence (e.g., at dinner) connoted vulnerability
      for distress and for poor school performance in both groups. The connotations of
      a few parenting dimensions varied by context and gender; these variations are
      discussed as are overall implications for future research and practice.

PMID- 15971768
TI  - Dimensions of adolescent rebellion: risks for academic failure among high- and
      low-income youth.
AB  - The central question addressed in this study was whether upper class, suburban
      teenagers can engage in various problem behaviors and still maintain adequate
      academic grades, because of environmental safety nets, unlike their low-income,
      inner-city counterparts. Three problem behavior dimensions were assessed among
      tenth graders, that is, substance use, delinquency, and low school engagement.
      Academic achievement was assessed in terms of grades across four major subjects.
      Variable-based analyses indicated unique links with grades for self-reported
      delinquency and school disengagement in high- and low-income samples, but for
      substance use only among the former. Person-based analyses showed that in both
      schools, grades were clearly compromised among youth with disturbances in all
      three problem domains. In addition, in the suburban school only, grades were low
      in the cluster characterized chiefly by high substance use. Results are discussed
      in terms of stereotypes regarding risks (or lack thereof) stemming from families'
      socioeconomic status; implications for theory and interventions are also
      considered.

PMID- 15971769
TI  - Developmental trajectories of offending: validation and prediction to young adult
      alcohol use, drug use, and depressive symptoms.
AB  - This longitudinal study extended previous work of Wiesner and Capaldi by
      examining the validity of differing offending pathways and the prediction from
      the pathways to substance use and depressive symptoms for 204 young men. Findings
      from this study indicated good external validity of the offending trajectories.
      Further, substance use and depressive symptoms in young adulthood (i.e., ages 23
      24 through 25-26 years) varied depending on different trajectories of offending
      from early adolescence to young adulthood (i.e., ages 12-13 through 23-24 years),
      even after controlling for antisocial propensity, parental criminality,
      demographic factors, and prior levels of each outcome. Specifically, chronic high
      level offenders had higher levels of depressive symptoms and engaged more often
      in drug use compared with very rare, decreasing low-level, and decreasing high
      level offenders. Chronic low-level offenders, in contrast, displayed fewer
      systematic differences compared with the two decreasing offender groups and the
      chronic high-level offenders. The findings supported the contention that varying
      courses of offending may have plausible causal effects on young adult outcomes
      beyond the effects of an underlying propensity for crime.

PMID- 15971770
TI  - Learning multiview face subspaces and facial pose estimation using independent
      component analysis.
AB  - An independent component analysis (ICA) based approach is presented for learning
      view-specific subspace representations of the face object from multiview face
      examples. ICA, its variants, namely independent subspace analysis (ISA) and
      topographic independent component analysis (TICA), take into account higher order
      statistics needed for object view characterization. In contrast, principal
      component analysis (PCA), which de-correlates the second order moments, can
      hardly reveal good features for characterizing different views, when the training
      data comprises a mixture of multiview examples and the learning is done in an
      unsupervised way with view-unlabeled data. We demonstrate that ICA, TICA, and ISA
      are able to learn view-specific basis components unsupervisedly from the mixture
      data. We investigate results learned by ISA in an unsupervised way closely and
      reveal some surprising findings and thereby explain underlying reasons for the
      emergent formation of view subspaces. Extensive experimental results are
      presented.

PMID- 15971771
TI  - Reconstruction of nonuniformly sampled images in spline spaces.
AB  - This paper presents a novel approach to the reconstruction of images from
      nonuniformly spaced samples. This problem is often encountered in digital image
      processing applications. Nonrecursive video coding with motion compensation,
      spatiotemporal interpolation of video sequences, and generation of new views in
      multicamera systems are three possible applications. We propose a new
      reconstruction algorithm based on a spline model for images. We use
      regularization, since this is an ill-posed inverse problem. We minimize a cost
      function composed of two terms: one related to the approximation error and the
      other related to the smoothness of the modeling function. All the processing is
      carried out in the space of spline coefficients; this space is discrete, although
      the problem itself is of a continuous nature. The coefficients of regularization
      and approximation filters are computed exactly by using the explicit expressions
      of B-spline functions in the time domain. The regularization is carried out
      locally, while the computation of the regularization factor accounts for the
      structure of the nonuniform sampling grid. The linear system of equations
      obtained is solved iteratively. Our results show a very good performance in
      motion-compensated interpolation applications.

PMID- 15971772
TI  - Blind deconvolution of images using optimal sparse representations.
AB  - The relative Newton algorithm, previously proposed for quasi-maximum likelihood
      blind source separation and blind deconvolution of one-dimensional signals is
      generalized for blind deconvolution of images. Smooth approximation of the
      absolute value is used as the nonlinear term for sparse sources. In addition, we
      propose a method of sparsification, which allows blind deconvolution of arbitrary
      sources, and show how to find optimal sparsifying transformations by supervised
      learning.

PMID- 15971773
TI  - Image reconstruction by linear programming.
AB  - One way of image denoising is to project a noisy image to the subspace of
      admissible images derived, for instance, by PCA. However, a major drawback of
      this method is that all pixels are updated by the projection, even when only a
      few pixels are corrupted by noise or occlusion. We propose a new method to
      identify the noisy pixels by l1-norm penalization and to update the identified
      pixels only. The identification and updating of noisy pixels are formulated as
      one linear program which can be efficiently solved. In particular, one can apply
      the upsilon trick to directly specify the fraction of pixels to be reconstructed.
      Moreover, we extend the linear program to be able to exploit prior knowledge that
      occlusions often appear in contiguous blocks (e.g., sunglasses on faces). The
      basic idea is to penalize boundary points and interior points of the occluded
      area differently. We are also able to show the upsilon property for this extended
      LP leading to a method which is easy to use. Experimental results demonstrate the
      power of our approach.

PMID- 15971774
TI  - Fast incorporation of optical flow into active polygons.
AB  - In this paper, we first reconsider, in a different light, the addition of a
      prediction step to active contour-based visual tracking using an optical flow and
      clarify the local computation of the latter along the boundaries of continuous
      active contours with appropriate regularizers. We subsequently detail our
      contribution of computing an optical flow-based prediction step directly from the
      parameters of an active polygon, and of exploiting it in object tracking. This is
      in contrast to an explicitly separate computation of the optical flow and its ad
      hoc application. It also provides an inherent regularization effect resulting
      from integrating measurements along polygon edges. As a result, we completely
      avoid the need of adding ad hoc regularizing terms to the optical flow
      computations, and the inevitably arbitrary associated weighting parameters. This
      direct integration of optical flow into the active polygon framework
      distinguishes this technique from most previous contour-based approaches, where
      regularization terms are theoretically, as well as practically, essential. The
      greater robustness and speed due to a reduced number of parameters of this
      technique are additional and appealing features.

PMID- 15971775
TI  - Multidimensional orthogonal filter bank characterization and design using the
      Cayley transform.
AB  - We present a complete characterization and design of orthogonal infinite impulse
      response (IIR) and finite impulse response (FIR) filter banks in any dimension
      using the Cayley transform (CT). Traditional design methods for one-dimensional
      orthogonal filter banks cannot be extended to higher dimensions directly due to
      the lack of a multidimensional (MD) spectral factorization theorem. In the
      polyphase domain, orthogonal filter banks are equivalent to paraunitary matrices
      and lead to solving a set of nonlinear equations. The CT establishes a one-to-one
      mapping between paraunitary matrices and para-skew-Hermitian matrices. In
      contrast to the paraunitary condition, the para-skew-Hermitian condition amounts
      to linear constraints on the matrix entries which are much easier to solve. Based
      on this characterization, we propose efficient methods to design MD orthogonal
      filter banks and present new design results for both IIR and FIR cases.

PMID- 15971776
TI  - Use of multiresolution wavelet feature pyramids for automatic registration of
      multisensor imagery.
AB  - The problem of image registration, or the alignment of two or more images
      representing the same scene or object, has to be addressed in various disciplines
      that employ digital imaging. In the area of remote sensing, just like in medical
      imaging or computer vision, it is necessary to design robust, fast, and widely
      applicable algorithms that would allow automatic registration of images generated
      by various imaging platforms at the same or different times and that would
      provide subpixel accuracy. One of the main issues that needs to be addressed when
      developing a registration algorithm is what type of information should be
      extracted from the images being registered, to be used in the search for the
      geometric transformation that best aligns them. The main objective of this paper
      is to evaluate several wavelet pyramids that may be used both for invariant
      feature extraction and for representing images at multiple spatial resolutions to
      accelerate registration. We find that the bandpass wavelets obtained from the
      steerable pyramid due to Simoncelli performs best in terms of accuracy and
      consistency, while the low-pass wavelets obtained from the same pyramid give the
      best results in terms of the radius of convergence. Based on these findings, we
      propose a modification of a gradient-based registration algorithm that has
      recently been developed for medical data. We test the modified algorithm on
      several sets of real and synthetic satellite imagery.

PMID- 15971777
TI  - Rotation-invariant multiresolution texture analysis using radon and wavelet
      transforms.
AB  - A new rotation-invariant texture-analysis technique using Radon and wavelet
      transforms is proposed. This technique utilizes the Radon transform to convert
      the rotation to translation and then applies a translation-invariant wavelet
      transform to the result to extract texture features. A kappa-nearest neighbors
      classifier is employed to classify texture patterns. A method to find the optimal
      number of projections for the Radon transform is proposed. It is shown that the
      extracted features generate an efficient orthogonal feature space. It is also
      shown that the proposed features extract both of the local and directional
      information of the texture patterns. The proposed method is robust to additive
      white noise as a result of summing pixel values to generate projections in the
      Radon transform step. To test and evaluate the method, we employed several sets
      of textures along with different wavelet bases. Experimental results show the
      superiority of the proposed method and its robustness to additive white noise in
      comparison with some recent texture-analysis methods.

PMID- 15971778
TI  - Space-dependent color gamut mapping: a variational approach.
AB  - Gamut mapping deals with the need to adjust a color image to fit into the
      constrained color gamut of a given rendering medium. A typical use for this tool
      is the reproduction of a color image prior to its printing, such that it exploits
      best the given printer/medium color gamut, namely the colors the printer can
      produce on the given medium. Most of the classical gamut mapping methods involve
      a pixel-by-pixel mapping and ignore the spatial color configuration. Recently
      proposed spatial-dependent approaches for gamut mapping are either based on
      heuristic assumptions or involve a high computational cost. In this paper, we
      present a new variational approach for space-dependent gamut mapping. Our
      treatment starts with the presentation of a new measure for the problem, closely
      related to a recent measure proposed for Retinex. We also link our method to
      recent measures that attempt to couple spectral and spatial perceptual measures.
      It is shown that the gamut mapping problem leads to a quadratic programming
      formulation, guaranteed to have a unique solution if the gamut of the target
      device is convex. An efficient numerical solution is proposed with promising
      results.

PMID- 15971779
TI  - Anti-collusion forensics of multimedia fingerprinting using orthogonal
      modulation.
AB  - Digital fingerprinting is a method for protecting digital data in which
      fingerprints that are embedded in multimedia are capable of identifying
      unauthorized use of digital content. A powerful attack that can be employed to
      reduce this tracing capability is collusion, where several users combine their
      copies of the same content to attenuate/remove the original fingerprints. In this
      paper, we study the collusion resistance of a fingerprinting system employing
      Gaussian distributed fingerprints and orthogonal modulation. We introduce the
      maximum detector and the thresholding detector for colluder identification. We
      then analyze the collusion resistance of a system to the averaging collusion
      attack for the performance criteria represented by the probability of a false
      negative and the probability of a false positive. Lower and upper bounds for the
      maximum number of colluders K(max) are derived. We then show that the detectors
      are robust to different collusion attacks. We further study different sets of
      performance criteria, and our results indicate that attacks based on a few dozen
      independent copies can confound such a fingerprinting system. We also propose a
      likelihood-based approach to estimate the number of colluders. Finally, we
      demonstrate the performance for detecting colluders through experiments using
      real images.

PMID- 15971780
TI  - Multipurpose image watermarking algorithm based on multistage vector
      quantization.
AB  - The rapid growth of digital multimedia and Internet technologies has made
      copyright protection, copy protection, and integrity verification three important
      issues in the digital world. To solve these problems, the digital watermarking
      technique has been presented and widely researched. Traditional watermarking
      algorithms are mostly based on discrete transform domains, such as the discrete
      cosine transform, discrete Fourier transform (DFT), and discrete wavelet
      transform (DWT). Most of these algorithms are good for only one purpose.
      Recently, some multipurpose digital watermarking methods have been presented,
      which can achieve the goal of content authentication and copyright protection
      simultaneously. However, they are based on DWT or DFT. Lately, several robust
      watermarking schemes based on vector quantization (VQ) have been presented, but
      they can only be used for copyright protection. In this paper, we present a novel
      multipurpose digital image watermarking method based on the multistage vector
      quantizer structure, which can be applied to image authentication and copyright
      protection. In the proposed method, the semi-fragile watermark and the robust
      watermark are embedded in different VQ stages using different techniques, and
      both of them can be extracted without the original image. Simulation results
      demonstrate the effectiveness of our algorithm in terms of robustness and
      fragility.

PMID- 15971781
TI  - Background learning for robust face recognition with PCA in the presence of
      clutter.
AB  - We propose a new method within the framework of principal component analysis
      (PCA) to robustly recognize faces in the presence of clutter. The traditional
      eigenface recognition (EFR) method, which is based on PCA, works quite well when
      the input test patterns are faces. However, when confronted with the more general
      task of recognizing faces appearing against a background, the performance of the
      EFR method can be quite poor. It may miss faces completely or may wrongly
      associate many of the background image patterns to faces in the training set. In
      order to improve performance in the presence of background, we argue in favor of
      learning the distribution of background patterns and show how this can be done
      for a given test image. An eigenbackground space is constructed corresponding to
      the given test image and this space in conjunction with the eigenface space is
      used to impart robustness. A suitable classifier is derived to distinguish
      nonface patterns from faces. When tested on images depicting face recognition in
      real situations against cluttered background, the performance of the proposed
      method is quite good with fewer false alarms.

PMID- 15971782
TI  - Nurses need business sense.

PMID- 15971783
TI  - Stimulating discussion.

PMID- 15971784
TI  - The importance of diversity.

PMID- 15971785
TI  - Supported, not sidelined.

PMID- 15971788
TI  - Payment. Ready, set, audit. Searching for overpayments, new Medicare contractors
      set out to scour hospital bills.
AB  - A new team of federal auditors this month starts combing through Medicare bills
      in three states looking for overpayments. If the three-year pilot is deemed a
      success, it could mean more scrutiny for hospitals nationwide.

PMID- 15971789
TI  - Access & coverage. Campus coverage. Uninsured and underinsured students add to
      financial woes facing university hospitals.

PMID- 15971790
TI  - Quality. Around the clock care. With hospitalists on board, patients get 24-hour
      physician attention.
AB  - Hospitals & Health Network's second installment of a series offering proven
      techniques to improve quality and reduce medical errors profiles the growing
      hospitalist movement.

PMID- 15971791
TI  - Workforce. The melting pot. It's one thing to build a diverse workforce; the next
      challenge is ensuring staff get along.

PMID- 15971792
TI  - Patient care. Time for tea. As insurance kicks in and patient demand grows,
      alternative therapy is hard to ignore.
AB  - A growing number of hospitals--and payers--are giving thumbs up to alternative
      therapies as a way to treat ailing patients. But not everyone agrees that the
      techniques are legitimate solutions.

PMID- 15971793
TI  - Workforce. Teachers wanted. The nursing shortage may worsen in years to come as
      faculty positions go unfilled.
AB  - The nursing shortage could worsen because of a dearth of educators. More than 60
      percent of baccalaureate programs say they have faculty openings, forcing them to
      turn away students. Experts say better pay and more use of technology could help.

PMID- 15971794
TI  - Finance. Doctors pitch in. To get more cash coming through the door, hospitals
      ask physicians to improve billing.

PMID- 15971795
TI  - Followership. Leading is a skill; so is following.

PMID- 15971796
TI  - Are you looking for a fresh start with your MDs?
AB  - This spring saw a welcome thaw in the icy relations between some hospitals and
      physicians, as it dawns on both sides that cooperation, not alienation, is
      essential for them to flourish. By nurturing new kinds of alliances and reviving
      some old but fallow practices, doctors and physicians expect to reap a bouquet of
      mutual rewards.

PMID- 15971797
TI  - Reporting infections. Mandatory vs. voluntary debate heats up as states enact
      legislation.
AB  - As more states mandate the reporting of health care-acquired infections and CMS
      spearheads a voluntary reporting initiative, hospitals ask: Is a patchwork of
      state regulations better than a nationwide mandatory or voluntary system? And
      when does all of this lead to "analysis paralysis," hindering hospitals'
      performance-improvement efforts?

PMID- 15971798
TI  - Finding the right prescription.
AB  - Demand for pharmacists continues to outpace supply, and with competition from
      commercial chains intensifying, hospitals' staffing woes won't ease any time
      soon. To fill the void, hospital executives are considering a number of
      aggressive steps, exploring everything from better pay and benefits to
      outsourcing to technological breakthroughs.

PMID- 15971799
TI  - Business issues in the pharmacy. Managing pharmacy costs.
AB  - With the annual inflation rate in their pharmacies at or near double-digits,
      hospital leaders are demanding better data, questioning why drug formularies are
      often ignored and urging pharmacists to take the initiative in identifying ways
      to save on costs.

PMID- 15971800
TI  - Spending spree. Big HIT: health information technology enjoys a growth spurt;
      still coming up short.

PMID- 15971801
TI  - Straight talk. A "quality" story--explaining IT needs to Wall Street.

PMID- 15971802
TI  - Three approaches to ROI.

PMID- 15971803
TI  - The case for funding. Wall Street should support health care IT investments.

PMID- 15971804
TI  - Hendra virus under the microscope.

PMID- 15971805
TI  - Disaster management--involvement of the veterinary profession?

PMID- 15971806
TI  - Practice insights.

PMID- 15971807
TI  - Exotic animal diseases bulletin. Interesting global disease events in 2004.

PMID- 15971808
TI  - Letter from Europe.

PMID- 15971809
TI  - Postcard from Tanzania.

PMID- 15971810
TI  - Killed vaccine response.

PMID- 15971812
TI  - Ferret fanatic.

PMID- 15971811
TI  - Heartwater insights.

PMID- 15971813
TI  - Diagnostic accuracy in the new millennium.

PMID- 15971814
TI  - The veterinary pharmacovigilance program of the APVMA.
AB  - This paper provides an overview of the Australian Pesticides and Veterinary
      Medicines Authority's (APVMA) Adverse Experience Reporting Program for veterinary
      medicines (AERP Vet). It outlines the history of the AERP Vet and how the program
      investigates adverse experience reports received from veterinarians, product
      registrants and members of the public. The benefits to veterinarians of such a
      program are highlighted and include the ability to trust in the safety, quality
      and efficacy of the veterinary drugs that they handle and administer daily.

PMID- 15971815
TI  - Depression, anorexia and abdominal pain in a young dog with an abdominal mass.

PMID- 15971816
TI  - The prevalence of feline A/B blood types in the Sydney region.
AB  - OBJECTIVE: To determine the distribution of A/B blood types in pedigree and
      crossbred cats in the Sydney region, and to estimate the associated risk of
      administering incompatible blood in an unmatched random transfusion. DESIGN: A
      prospective/retrospective study of blood specimens collected from both sick and
      healthy cats. MATERIALS AND METHODS: Blood was collected from 355 cats from the
      Sydney region over a 12-year period from 1992 to 2003. Specimens were obtained
      from 187 domestic crossbred cats (short and long-haired) and 168 pedigree cats.
      The blood type of each cat was determined by one of three different laboratories
      using standard methods that varied over the duration of the survey. RESULTS: The
      distributions of blood types obtained by the three laboratories were not
      significantly different. The prevalence of type-A, type-B and type-AB blood types
      in crossbred cats was 62%, 36% and 1.6%, respectively. This is the highest
      percentage of type-B cats so far reported for an outbred population of domestic
      cats, and is significantly higher than the 26% reported previously for cats in
      the Brisbane region. The calculated frequency for the type-B allele assuming
      Hardy-Weinberg equilibrium for this feline population is 0.60; the corresponding
      frequency of the type-A allele is thus approximately 0.40. The calculated
      proportion of random transfusions from this population giving rise to an
      incompatible blood transfusion is 46%, with half of these being life-threatening
      events. The calculated proportion of random matings from this population at risk
      for developing neonatal isoerythrolysis is 23%. The distribution of A and B blood
      types for pedigree cats was in general agreement with data reported previously
      for cats in North America and Europe, suggesting that the distribution of blood
      types in these purebred populations is relatively consistent throughout the
      world. CONCLUSIONS: The prevalence of type B cats in the owned domestic and
      pedigree cat population is so high that blood typing or cross matching prior to
      transfusion should be mandatory, except in Siamese/Oriental cats.

PMID- 15971817
TI  - Equine endotoxaemia--a state-of-the-art review of therapy.
AB  - The pathophysiology of endotoxaemia, a leading cause of death in the horse, is
      beginning to be understood in greater detail. Endotoxin may be absorbed into the
      systemic circulation in a number of different ways: most commonly the body's
      normal defense mechanisms are disrupted or bypassed, or the normal clearance
      mechanisms overwhelmed. Following this wide-spread effects are observed, although
      the most significant are seen in the cardiovascular system. Fever, arterial
      hypoxaemia and signs of abdominal pain are also common. With increased
      understanding of the disease new therapeutic agents have become available,
      however, while the newer agents offer some advantages it is important to
      recognise that supportive care is the mainstay of treatment for endotoxaemia.
      Supportive care consists of aggressive fluid therapy (crystalloid, colloid and
      hypertonic), the administration of non-steroidal antiinflammatory drugs and,
      where appropriate, antimicrobials. The principles of supportive care are
      discussed in detail. Other therapies such as hyperimmune plasma, polymyxin B,
      pentoxifylline, dimethyl sulfoxide and heparin are commonly used in the treatment
      of equine endotoxaemia and their use is reviewed here. Furthermore, newer agents
      such as anti-tumour necrosis factor antibodies, detergent, activated protein C
      and insulin, which have yet to gain widespread acceptance but may have an
      important role in the treatment of endotoxaemia in the future, are examined.

PMID- 15971818
TI  - The surgical management of oesophageal obstruction in a horse.

PMID- 15971819
TI  - Feline immunodeficiency virus vaccine issues.

PMID- 15971820
TI  - Chronic cystic ovarian disease in a Holstein cow.
AB  - Cystic ovarian follicles are commonly found during rectal examination of early
      postpartum dairy cows, usually presenting with anoestrus and occasionally
      nymphomania. Most cases self cure with time, or respond to exogenous hormonal
      treatment. This case report describes a refractory case in a Holstein cow in
      which a novel treatment approach was used. A gonadotrophin releasing hormone
      agonist implant was inserted for 180 d in an attempt to suppress pituitary
      gonadotrophin output, arrest abnormal ovarian follicle growth and prevent
      steroidogenesis. Frequent serial blood samples were collected before and after
      implant insertion to monitor changes in pulse release of luteinising hormone.
      Follow up ultrasound scans and blood samples were done to monitor ovarian
      structures; progesterone and oestradiol were collected at various times over the
      180 d period. A normal, cycling herdmate was enrolled as a control. Prior to
      implant insertion, high frequency and low amplitude luteinising hormone pulses
      were detected in the cystic cow. Insertion was followed by a sustained surge in
      the release of luteinising hormone in both cows, but ovulation was not induced in
      the cystic cow. Plasma oestradiol levels remained consistently elevated and signs
      of oestrous behaviour were observed. Long term gonadotrophin releasing hormone
      agonist treatment failed to suppress either ovarian steroid production or cause
      regression of the cysts by 180 d.

PMID- 15971821
TI  - Volvulus of the ascending colon and caecum in a horse secondary to absence of
      dorsal mesenteric attachments.

PMID- 15971822
TI  - Interaction of saddle girth construction and tension on respiratory mechanics and
      gas exchange during supramaximal treadmill exercise in horses.
AB  - OBJECTIVE: To determine the effect of girth construction and tension on
      respiratory mechanics and gas exchange during supramaximal treadmill exercise in
      horses. METHODS: Six healthy detrained Thoroughbred horses were exercised on a
      treadmill inclined at 10% at 110% VO2max. Horses were instrumented for
      respiratory mechanics and gas exchange studies, and data were recorded during
      incremental exercise tests. The animals were exercised for 2 min at 40% VO2max,
      and samples and measurements were collected at 1 min 45 sec. After 2 min, speed
      was increased to that estimated at 110% VO2max and data was collected at 45 sec,
      90 sec and every 30 sec thereafter at this speed until the horses fatigued.
      Horses were run on three occasions with the same racing saddle and saddle packing
      but using two different girths, either an elastic girth (EG) or a standard canvas
      girth (SCG) which is nonelastic. A run with 5 kg tension applied to a standard
      canvas girth was the control for each horse, with additional runs at 15 kg using
      either the standard canvas girth or using the elastic girth. The runs were
      randomised and tensions applied were measured at end exhalation whilst at rest.
      RESULTS: Increasing girth tension was not associated with changes in respiratory
      mechanical or gas exchange properties. Although girths tightened to 15 kg tension
      had short run to fatigue times this was not found to be significantly different
      to girths set at 5 kg resting tension. Girth tensions declined at end exhalation
      in horses nearing fatigue. CONCLUSIONS: Loss in performance associated with high
      girth tensions is not due to alteration of respiratory mechanics. Loss in
      performance may be related to inspiratory muscles working at suboptimal lengths
      due to thoracic compression or compression of musculature around the chest.
      However, these changes are not reflected in altered respiratory mechanical or gas
      exchange properties measured during tidal breathing during supramaximal exercise.
      Other factors may hasten the onset of fatigue when horses exercise with tight
      girths and further studies are required to determine why excessively tight girths
      affect performance.

PMID- 15971823
TI  - Comparison of girth materials, girth tensions and their effects on performance in
      racehorses.
AB  - OBJECTIVE: To compare the effect of girth materials and commonly used girth
      tensions on athletic performance of race-horses and to test the length tension
      properties of commercially available girths. PROCEDURE: Seven horses were
      exercised at speeds to produce 95% of maximal heart rates on 15 occasions using a
      randomised block design, and girthed with 5 different girths at 3 nominal
      tensions of 6, 12 or 18 kg. The girths used were a standard elastic race girth,
      an 'American' elastic race girth, an elastic race girth twice the normal width, a
      standard canvas race girth and a canvas race girth at twice the normal width.
      Tension in the girth was recorded continuously using an in-line load cell
      connected to a physiograph. Horses ran to fatigue on a treadmill inclined at 10%
      slope. Tensions were measured at peak inhalation (T/inh) and exhalation (T/exh),
      recorded at rest (rest) and during exercise (ex). An analysis of variance was
      used to compare the mean run to fatigue times (RTFT) between girth types and
      tensions, multiple pair-wise comparisons were then carried out using Tukey's test
      where significant differences were found. The length-tension relationships of
      five commercially available girths for training and racing of Thoroughbred
      racehorses were studied by the application of standardized weights in series to
      multiple samples of each type of girth. Measurements were taken in a controlled
      environment and analysis of variance was used to compare the means for length
      tension of each girth type. RESULTS: The elastic and the 'American' elastic
      girths produced significantly longer RTFT when compared to the standard canvas
      girth (P = 0.01 and P = 0.001 respectively). Also girths tensioned at Texhrest 6
      kg and Texhrest 12 kg produced significantly longer RTFT than when girthed at
      Texhrest 18 kg (P = 0.03 and P = 0.08 respectively). There were significant
      differences between the commercially available girth types at each tension (P <
      0.05), but differences were not significant between girths of the same type.
      Girths with an elastic component reached their peak for maximum extension at 14.5
      kg and thereafter their extension declined. CONCLUSION: The type of girth and the
      tension at which it is applied affects athletic performance. Lower girth tensions
      and the use of elastic materials in the girth would appear to optimise
      performance. However according to this study and our previous study, none of the
      commercially available girths studied would adequately protect against the
      potentially detrimental effects of overtightening on athletic performance.

PMID- 15971824
TI  - Temperature changes in dental pulp associated with use of power grinding
      equipment on equine teeth.
AB  - OBJECTIVE: To quantify the temperature changes in the dental pulp associated with
      equine dental procedures using power grinding equipment. DESIGN: A matrix
      experimental design with replication on the same sample was followed to allow the
      following independent variables to be assessed: horse age (young or old), tooth
      type (premolar or molar), powered grinding instrument (rotating disc or die
      grinder), grinding time (15 or 20 seconds) and the presence or absence of water
      coolant. PROCEDURE: Sound premolar and molar teeth from a 6-year-old horse and a
      15-year-old horse, which had been removed postmortem, were sectioned parallel to
      the occlusal plane to allow placement of a miniature thermocouple at the level of
      the dental pulp. The maximum temperature increase, the time taken to reach this
      maximum and the cooling time were measured (n=10 in each study). The teeth were
      placed in a vice and the instrument used on the tooth as per clinical situation.
      RESULTS: Significant differences were recorded for horse age (P < 0.001),
      instrument type (P < 0.001), grinding time (P < 0.001) and presence or absence of
      coolant (P < 0.001). There was no significant difference for tooth type.
      CONCLUSION: Thermal insult to the dental pulp from the use of power instruments
      poses a significant risk to the tooth. This risk can be reduced or eliminated by
      appropriate selection of treatment time and by the use of water irrigation as a
      coolant. The increased dentine thickness in older horses appears to mitigate
      against thermal injury from frictional heat.

PMID- 15971825
TI  - Effect of withholding macromolecules on the duration of intestinal permeability
      to colostral IgG in foals.
AB  - OBJECTIVE: To quantify absorption of colostral IgG by healthy neonatal foals and
      to test the hypothesis that delayed ingestion of macromolecules prolongs the
      duration of intestinal permeability to immunoglobulins (Ig) in newborn foals.
      ANIMALS: Thirteen mixed breed foals. PROCEDURE: Foals were randomly assigned to
      two treatment groups, which were fed either a glucose-electrolyte solution or a
      commercial milk replacer for 12 h after birth, before being fed a known amount of
      colostral IgG. A control group was fed a known amount of colostral IgG from
      birth. The efficiency of IgG absorption was calculated following determination of
      plasma IgG concentration for each foal. RESULTS: Foals given colostrum
      immediately after birth transferred approximately 51% of ingested IgG into their
      vascular space. Delayed colostral ingestion significantly reduced the amount of
      IgG absorbed by foals. Withholding macromolecules for 12 h had no effect on the
      subsequent efficiency of IgG absorption. CONCLUSIONS: Colostrum should be
      supplied to foals within 12 h of birth for best uptake of Ig. The type of fluid
      administered to foals before the ingestion of colostrum does not influence
      subsequent absorption of Ig, suggesting that the process of gut closure in foals
      is not mediated by a finite capacity for macromolecular uptake.

PMID- 15971826
TI  - Mortalities in bobby calves associated with long distance transport.
AB  - OBJECTIVE: To investigate how distance of transportation and time of year affects
      mortality of bobby calves. METHOD: The overall mortality of bobby calves
      transported by road to an abattoir in Northern Victoria was investigated by the
      analysis of mortality data from 1998 to 2000 from the abattoir records. RESULTS:
      Mortality of bobby calves increased exponentially with distance of transportation
      to the abattoir. The association between distance travelled and mortality was
      greatest in August. The increased mortality associated with greater distance
      travelled occurred during transportation rather than after arrival at the
      abattoir. The highest mortality of bobby calves was seen in October, followed by
      September, and the lowest was observed in August. CONCLUSION: Limits on the
      distance of transportation of bobby calves should be incorporated into future
      codes of practice to reduce the mortality of bobby calves.

PMID- 15971827
TI  - Effect of compliance with recommended calf-rearing practices on control of bovine
      Johne's disease.
AB  - OBJECTIVE: To assess the degree of compliance with recommended management
      procedures for the control of bovine Johne's disease and study the relationship
      between aspects of calf management and testing/disease outcomes in the herds.
      PROCEDURE: Fifty-four south Gippsland dairy herds participating in the Victorian
      bovine Johne's disease test and control program were visited between July and
      November 2002 and an audit of calf rearing practices was conducted. The results
      of testing completed under the program were analysed for each of the herds.
      Twenty seven management factors were examined for a relationship with the
      presence of clinical cases of Johne's disease or cattle with positive ELISA test
      results that were born after the completion of the second whole herd test.
      Logistic regression was used to examine the strength of relationships between the
      management practices and the frequency with which new cases of Johne's disease
      arose. RESULTS AND CONCULSIONS: Calves were removed from their dams within 12
      hours of birth in only 17 (31.5%) of the herds. However, in all but one herd the
      calves were removed within 24 hours of birth. In 42 herds (77.8%) calf rearing
      facilities were adequately separated from adult cattle and the faeces from adult
      cattle. In 41 herds (75.9%) calves up to the age of 12 months were grazed on
      paddocks that were free of manure or effluent from adult cattle. However, in only
      10 (18.5%) of the herds were all three of these calf management practices
      applied. Feeding whole milk containing antibiotic residues, or providing water
      for calves from birth, were found to have statistically significant associations
      with an increased occurrence of cases of bovine Johne's disease in the study
      herds. The practice of allowing cows to calve in a paddock was found to be
      associated with reduced occurrence of bovine Johne's disease. These associations
      were still found after analysis that included herd size, the number of clinical
      cases that had occurred in the herds before the start of testing, the number of
      animals with positive ELISA tests that were detected at the first test and the
      number of years of participation in the test and cull program. Early separation
      of newborn calves from cows and grazing calves under 12 months of age in areas
      free of adult cattle were not found to be protective against Johne's disease.

PMID- 15971828
TI  - Synchronising oestrus with oestradiol benzoate after using a two-dose
      prostaglandin treatment to synchronise luteolysis in dairy heifers.
AB  - OBJECTIVE: To compare the reproductive performance and pattern of onset of
      oestrus in dairy heifers in which oestrous cycles were synchronised with two
      doses of prostaglandin (PG) F2alpha and oestrus was synchronised with oestradiol
      benzoate (ODB). PROCEDURE: Dairy heifers in two herds (herd A, n = 192; herd B, n
      = 267) were treated with two doses of an analogue of PGF2alpha (cloprostenol, 375
      microg, IM) 12 days apart. Heifers not detected in oestrus 48 h after the last
      dose of PGF2alpha were either left untreated (No ODB, n = 147) or treated with
      ODB (0.75 mg IM, n = 126). Onset of oestrus was monitored at 0, 24, 48, 80, 96
      and 120 h after the last dose of PGF2alpha Heifers were inseminated on detection
      of oestrus. RESULTS: After the last dose of PGF2alpha, oestrous detection rates
      at 80 h (43.5 vs 72.6%, P < 0.001), 96 h (74.1 vs 84.9%, P =0.025) and 120 h
      (78.2 vs 86.3%, P = 0.082) were less in the No ODB compared to the ODB heifers,
      respectively. Conception rates (percentage pregnant that were inseminated) were
      greater in the No ODB compared to the ODB heifers (64.3% vs 47.6%, respectively;
      P = 0.006), while pregnancy rates (percentage pregnant that were treated) were
      also greater in the No ODB compared to the ODB heifers, but differences were not
      significant (50.3% vs 41.1%, respectively; P = 0.068). CONCLUSION: Administration
      of ODB to heifers not in oestrus 48 h after a two-dose PGF2alpha treatment
      increases the percentage of heifers detected in oestrus by 80 h, 96 h and 120 h
      after treatment, by an estimated 29%, 11% and 8%, respectively. However,
      administration of ODB decreases conception rates by an estimated 17%, and may
      decrease pregnancy rates (estimated 9% difference). Results are consistent with
      the hypothesis that ODB can increase submission rates but reduce conception rates
      following a two dose treatment with PGF2alpha.

PMID- 15971829
TI  - Assessment of antibodies to rabbit haemorrhagic disease virus in fox serum as an
      indicator of infection in sympatric rabbit populations.
AB  - OBJECTIVE: To assess the value of foxes as indicators of rabbit haemorrhagic
      disease virus in sympatric populations of rabbits. DESIGN: Serum samples from 341
      foxes in central western New South Wales were tested for exposure to rabbit
      haemorrhagic disease virus using antibody cELISAs. Selected samples were tested
      for viral antigens by ELISA, viral nucleic acids by reverse transcriptase PCR and
      viral infectivity by rabbit inoculation. RESULTS: Antibodies against rabbit
      haemorrhagic disease virus were first detected in foxes 4 months after rabbit
      haemorrhagic disease was observed in rabbits in the same area. There was evidence
      of exposure of foxes to the virus in two subsequent years. A proportion of
      antibody positive, inconclusive and negative serum samples from foxes gave false
      positive results in an antigen ELISA for rabbit haemorrhagic disease virus. These
      serum samples were negative for viral nucleic acid by reverse transcriptase PCR
      and for infectious virus by rabbit inoculation. Liver samples from foxes were
      negative for viral antigens. CONCLUSIONS: Antibodies against rabbit haemorrhagic
      disease virus in fox serum can serve as an index of the occurrence of rabbit
      haemorrhagic disease in rabbit populations. Some fox serum samples exhibit false
      positive reactivity in an antigen ELISA for rabbit viral haemorrhagic disease
      virus.

PMID- 15971830
TI  - Molecular detection of Anaplasma platys in lice collected from dogs in Australia.

PMID- 15971831
TI  - A comparative field trial of cephalonium and cloxacillin for dry cow therapy for
      mastitis in Australian dairy cows.

PMID- 15971832
TI  - Otto Schmitt's legacy continues to reverbrate.

PMID- 15971833
TI  - Otto Schmitt's legacy continues to reverbrate.

PMID- 15971834
TI  - Otto Schmitt's legacy continues to reverbrate.

PMID- 15971835
TI  - Otto Schmitt's legacy continues to reverbrate.

PMID- 15971836
TI  - EMBS survey results.

PMID- 15971837
TI  - Entelos: predictive model systems for disease. Interview by Semahat S. Demir.

PMID- 15971838
TI  - Shape and function from motion in medical imaging: Part I.

PMID- 15971839
TI  - Key challenges in proteomics and proteoinformatics. Progress in proteins.

PMID- 15971840
TI  - Proteins and their shape strings. An exemplary computer representation of protein
      structure.

PMID- 15971841
TI  - Enabling proteomics discovery through visual analysis. The peptide permutation
      and protein prediction tool.
AB  - Proteins play a key role in cellular processes, making proteomics central to
      understanding systems biology. MS techniques provide a means to observe entire
      proteomes at a global level. Yet, high-throughput MS proteomics techniques
      generate data faster than it can currently be analyzed. The success of proteomics
      depends on high-throughput experimental techniques coupled with sophisticated
      visual analysis and data-mining methods. Visual analysis has been applied
      successfully in a number of fields plagued with huge, complex data sets and will
      likely be an important tool in proteomics discovery. PQuad, a novel visualization
      of MS proteomics data, provides powerful analysis capabilities that support a
      number of proteomic data applications. In particular, PQuad supports differential
      proteomics by simplifying the comparison of peptide sets from different
      experimental conditions as well as different protein identification or confidence
      scoring techniques. Finally, PQuad supports data validation and quality control
      by providing a variety of resolutions for huge amounts of data to reveal errors
      undetected by other methods.

PMID- 15971842
TI  - Does protein structure influence trypsin miscleavage? Using structural properties
      to predict the behavior of related proteins.

PMID- 15971843
TI  - Quantitative analysis of proteomics using data mining. An automated system for
      constructing assays quickly and precisely.

PMID- 15971844
TI  - Functional proteomics with biolinguistic methods. n-grams deliver sensitive
      portrayals of gene similarity.

PMID- 15971845
TI  - Optimization techniques for string selection and comparison problems in genomics.
      Applying integer programming and heuristic algorithms for improved solutions.

PMID- 15971846
TI  - Predicting secondary structures of proteins. Recognizing properties of amino
      acids with the logical analysis of data algorithm.

PMID- 15971847
TI  - Data mining in protein interactomics. Six computational research challenges and
      opportunities.

PMID- 15971848
TI  - Mining new protein-protein interactions. Using a hierarchical latent-variable
      model to determine the function of a functionally unknown protein.

PMID- 15971849
TI  - Open magnetic and electric graphic analysis.
AB  - The OMEGA software provides an analysis platform for user-independent, fast, and
      reproducible multimodal data analysis in one single software environment.
      Synergetic interactions pursued between the two functional imaging techniques
      fMRI and MEG use the morphological MRI recording as a basis for a common
      coordinate frame. In this way, direct interchange, comparison, and integration
      among the results of the different modalities have become feasible. The fMRI data
      analysis provides information about the localization of functional activity with
      low temporal resolution, whereas the MEG recording complements the corresponding
      time evolution with a high temporal resolution. The implementation of OMEGA
      allows the analyst to receive comprehensive MEG/fMRI results in a matter of
      minutes after the measurements have been completed. With OMEGA, the clinical
      researcher gets comprehensive information in a quick and standardized approach
      about the sites and the time course of neurological activation, which is useful
      for clinical applications and diagnostics.

PMID- 15971850
TI  - Medical data on demand with WebMIA.

PMID- 15971851
TI  - Science, technology, and the researcher.

PMID- 15971852
TI  - Cardiomyoplasty: the prospect of human stem cells.

PMID- 15971853
TI  - Multiple chemical sensitivity syndrome (MCS)--suggestions for an extension of the
      U.S. MCS-case definition.
AB  - PURPOSE: To validate and extend the US case definition for the Multiple Chemical
      Sensitivity Syndrome (MCS) from 1999 by a systematic literature-review. DATA
      SOURCE: MEDLINE-research from 1997 to August 2003, research in the Cochrane
      Library in August 2003, earlier reviews since 1997. STUDY SELECTION: Headings and
      abstracts were screened by one reviewer. All references dealing with multiple
      chemical sensitivities (MCS) which covered topics of interest such as symptom
      profiles, differential diagnostic procedures, etc. were included in the analysis.
      DATA EXTRACTION AND SYNTHESIS: Topic-specific data extraction and synthesis was
      done by one reviewer. Data interpretation was discussed by all other authors.
      RESULTS: Out of 1429 references 36 publications proved to be suitable for the
      review. The results can be summarized as follows: exposure-related symptoms
      associated with self-reported multiple chemical sensitivities can be divided into
      non-specific complaints of the central nervous system--CNS (main characteristics)
      and functional disturbances in other organ systems (optional complaints). There
      is a significant overlap of MCS, CFS and fibromyalgie. At present no standards
      for a diagnostic procedure based on the criteria outlined above are existing
      CONCLUSIONS: MCS should only be diagnosed in patients who are mainly suffering
      from exposure-related non-specific complaints of the Central nervous system. The
      suggested diagnostic procedure follows the guidelines for CFS which are extended
      by diagnostic clarification of functional disturbances in other organ systems.

PMID- 15971854
TI  - Mechanisms leading to post-supply water quality deterioration in rural Honduran
      communities.
AB  - Drinking water can become contaminated following its collection from communal
      sources such as wells and tap stands, as well as during its storage in the home.
      However, the mechanisms leading to contamination between the points of supply and
      consumption have not been well documented. This study carried out field-based
      experiments in three rural Honduran communities to investigate the potential for
      contamination through hand contact, method used to draw water, and dirty
      collection containers. The possibility of bacterial growth occurring in stored
      water was also considered. Hand-water contact was observed frequently during the
      collection and drawing of drinking water. Faecal contamination was present on 44%
      of women's fingertips tested during normal household activities, and this faecal
      material was easily transferred to water. An immediate deterioration in water
      quality was observed on filling collection containers. Faecal material was
      detected on cups and beakers used for drawing stored drinking water. Evidence was
      produced indicating that thermotolerant coliforms remain attached to the inner
      surface of clay storage containers after rinsing. Drinking-water quality
      deteriorates during collection and storage as a result of multiple factors linked
      to hygiene practices and circumstances. However, hands have the greatest
      potential to introduce contamination because of the constant risk of contact
      during household water management.

PMID- 15971855
TI  - Monitoring of Cryptosporidium and Giardia in the Vantaa river basin, southern
      Finland.
AB  - We compared two sampling methods to assess the contamination of the Vantaa river
      basin by Giardia cysts and Cryptosporidium oocysts: 10-1 grab samples, the common
      river mussel Anadonta piscinalis, were analysed for concentration of (oo)cysts
      from river water. The samples were collected 2-5 times in autumn 2001 from four
      wastewater treatment plants and four river water sites located downstream of the
      plants, and six times from raw water of a drinking water plant using the river as
      water source. The presence of Giardia and Cryptosporidium was analysed by IF
      microscopy and PCR. Both cysts and oocysts were detected at all sampling sites,
      but oocysts were more common than cysts in river water samples. In contrast,
      cysts were more common in A. piscinalis. Most Cryptosporidium-positive samples
      were of genotype 2 and Giardia were assemblage B. In river water, MPN of
      Escherichia coli did not correlate to the presence of (oo)cysts. In conclusion,
      low (oo)cyst counts were regularly identified in the Vantaa river basin which is
      contaminated by discharges of treated wastewater of human origin. In general,
      both methods to appropriate to detect (oo)cysts, but grab samples yielded more
      positive results. Grab sampling is also more practical and less expensive than
      analysis of A. piscinalis.

PMID- 15971856
TI  - DNA adduct formation of benzo[a]pyrene in white blood cells of workers exposed to
      polycyclic aromatic hydrocarbons.
AB  - The major DNA adducts of anti-benzo[a]pyrene diolepoxide (BPDE) were determined
      by high performance liquid chromatography with fluorescence detection (HPLC-FLD)
      in white blood cells (WBC) of workers exposed to benzo[a]pyrene (B[a]P). In
      addition, ambient concentrations of B[a]P at the workplace were determined by
      personal air sampling. Workers in a refractory setting were examined before
      (n=26) and 3 months after (n = 33) changing the production material (binding
      pitch). Furthermore, 9 coke oven workers were examined. The change in the
      production process in the refractory setting led to a decrease in the median of
      ambient B[a]P concentrations (0.14 to <0.07 microg/m3). The median of BPDE-DNA
      adduct levels in WBC also decreased from 0.9 adducts/10(8) nucleotides before
      changing the production material to <0.5 adducts/10(8) nucleotides 3 months
      afterwards. The B[a]P concentrations at the workplace for the coke oven workers
      were found to be significantly higher than in the refractory setting. However,
      BPDE-DNA adduct concentrations in coke oven workers and refractory setting
      workers showed no significant difference, which was probably due to the low
      number of studied subjects in the coke-oven setting. No significant differences
      could be observed for BPDE-DNA adduct levels between current smokers (n=21) and
      non-smokers (n=14; p = 0.93) from both plants. In addition, no correlation
      between B[a]P concentrations in the air and DNA adduct levels in refractory
      workers and in coke oven workers could be found (r = -0.03, p = 0.87). Because of
      the missing correlation between personal air sampling and BPDE-DNA adduct levels
      in WBC, the results may indicate that their formation is either influenced by
      other routes of exposure to B[a]P (e.g., skin absorption, dietary habits) or
      interindividual differences in their formation and repair.

PMID- 15971857
TI  - Assessment of DNA damage in nuclear medicine personnel--comparative study with
      the alkaline comet assay and the chromosome aberration test.
AB  - Despite much research over the last few decades, there still remains considerable
      uncertainty as to the genetic impact of ionizing radiation on human populations,
      particularly at low levels. The aim of the present study was to provide data on
      the genetic hazards due to occupational exposure of low doses of ionizing
      radiation in nuclear medicine departments. The assessment of primary DNA damage
      in peripheral blood leukocytes of medical staff was performed using the alkaline
      comet assay and the data obtained were compared with the results of conventional
      cytogenetic biodosimetry using the chromosome aberration (CA) test. Altogether
      120 subjects (60 exposed and 60 controls) participated in the study.
      Statistically significant increases in primary DNA damage and increased
      frequencies of CAs compared to controls were observed. Within the exposed
      population, significant inter-individual differences in DNA damage were found,
      indicating differences in genome sensitivity. Age and gender were not confounding
      factors, while smoking enhanced the levels of primary DNA damage only in control
      subjects, as revealed by both biomarkers studied. The present study suggests that
      genotoxic damage results from exposure to chronic low doses of ionizing radiation
      in nuclear medicine departments. Therefore, the exposed medical personnel should
      carefully comply with the radiation protection procedures and should minimize
      radiation exposure where possible to avoid potential genotoxic effects. The
      results obtained in this study point to the significance of biological indicators
      providing information on the actual risk to the radiation exposed individuals.
      According to our results, the alkaline comet assay and CA test are sensitive
      biomarkers that can be used as additional complements to physical dosimetry for
      assessing exposure to radiation in nuclear medicine personnel.

PMID- 15971858
TI  - Pyrethroids used indoor-ambient monitoring of pyrethroids following a pest
      control operation.
AB  - House dust and airborne particles (PM) were sampled before (T1) and 1 day (T2), 4
      6 months (T3) as well as 10-12 months (T4) after a pest control operation (PCO).
      Cyfluthrin was applied in 11, cypermethrin in 1, deltamethrin in three and
      permethrin in four interiors. The pyrethroid concentrations in house dust and PM
      were measured by GC/MS with a detection limit for all pyrethroids of 0.5 mg/kg
      house dust and of 1 ng/m3 PM for deltamethrin and permethrin and 3 ng/m3 PM for
      cyfluthrin and cypermethrin. A general background concentration of permethrin
      (95th percentile: 5.9 mg/kg) and cyfluthrin (95th percentile: 34.9 mg/kg) in
      house dust was found. In general, an appropriately performed PCO lead to an
      increase of pyrethroids in house dust as well as in PM, in some cases up to 1
      year after application. One day after the application the cyfluthrin
      concentration increased significantly from 0.25 (T1) to 33.8 mg/kg house dust
      (T2) and up to 4.9 ng/m3 in PM. The permethrin concentration increased
      significantly from 4.3 to 70 mg/kg in house dust and up to 18.1 ng/m3 in PM,
      deltamethrin increased to 54.5 mg/kg and 20.8 ng/m3 and cypermethrin to 14 mg/kg
      and 45.7 ng/m3. Thereafter a continuous decrease could be observed during the
      time course of 1 year. After 1 year the permethrin concentration in house dust
      was still 1/5 of the T2 concentration, whereas for cypermethrin and cyfluthrin
      only 1/14 and 1/23 of the T2 concentration were found. Deltamethrin was not
      detected at all after T2. Moreover, the data of this study showed significant,
      positive correlations between pyrethroids in house dust and in airborne particles
      especially one day after PCO.

PMID- 15971859
TI  - Short, thin asbestos fibers contribute to the development of human malignant
      mesothelioma: pathological evidence.
AB  - Based on animal studies, long and thin asbestos fibers (> or =8 microm in length
      and < or = 0.25 microm in width) have been postulated to be strongly carcinogenic
      inducing pleural malignant mesothelioma, while shorter, thicker fibers have been
      postulated to pose a lesser risk (Stanton hypothesis). The objective of this
      study is to test the validity of the Stanton hypothesis through direct pathologic
      analysis of human mesothelioma tissue. Digested bulk tissue samples, or ashed 25
      microm thick sections, or both, were prepared from lung and mesothelial tissues
      taken from 168 cases of human malignant mesothelioma. In these tissues, 10,575
      asbestos fibers (4820 in the lung and 5755 in mesothelial tissues (1259 in
      fibrotic serosa and 4496 in mesotheliomatous tissue)) were identified by high
      resolution analytical electron microscopy. Dimensions of these asbestos fibers
      were measured in printed electron micrographs. Results were as follows: (1) long,
      thin asbestos fibers consistent with the Stanton hypothesis comprised only 2.3%
      of total fibers (247 / 10,575) in these tissues; (2) the majority (89.4%) of the
      fibers in the tissues examined were shorter than or equal to 5 microm in length
      (9454 of 10,575), and generally (92.7%) smaller than or equal to 0.25 microm in
      width (9808 of 10,575). (3) Among asbestos types detected in the lung and
      mesothelial tissues, chrysotile was the most common asbestos type to be
      categorized as short, thin asbestos fibers. (4) Compared with digestion technique
      of the bulk tissue, ashing technique of the tissue section was more effective to
      detect short, thin fibers. We conclude that contrary to the Stanton hypothesis,
      short, thin, asbestos fibers appear to contribute to the causation of human
      malignant mesothelioma. Such fibers were the predominant fiber type detected in
      lung and mesothelial tissues from human mesothelioma patients. These findings
      suggest that it is not prudent to take the position that short asbestos fibers
      convey little risk of disease.

PMID- 15971860
TI  - Chemopreventive properties of trans-resveratrol against the cytotoxicity of
      chloroacetanilide herbicides in vitro.
AB  - The beneficial effect of trans-resveratrol (RESV) on health is well documented.
      Our aim was to study the putative preventive effect of RESV on the cytotoxicity
      of frequently used herbicides (alachlor, acetochlor). Estrogen receptor positive
      (ER+) MCF-7 human mammary carcinoma, HepG2 (ER+) human hepatocellular carcinoma
      and VERO estrogen receptor negative (ER-) non-transformed monkey fibroblast cell
      lines were treated with alachlor and acetochlor (2-500 microg/ml) as toxic
      agents, and RESV (10 microM) as preventive agent. The MTT dye reduction assay was
      performed to test cytotoxicity, and flow cytometry to test cell proliferation and
      apoptosis. RESV is not cytotoxic in the concentration range of 1-100 microM on
      neither cell lines examined after 24 h, but cytotoxic on Vero and MCF-7 cells at
      100 microM after 48h, and on all three cell lines after 72 h. On both ER+ cell
      lines a stimulation of viability occurs in the low concentration range (0.5-12.5
      microM) as detected by the MTT assay. Cell cycle analysis of the culture shows a
      significant increase of S-phase cells at low concentrations of RESV (10-50
      microM) and a decrease in the 100-200 microM concentration range. The ratio of
      apoptotic cells significantly increases after the administration of 50 microM
      RESV, depending on the incubation time. The cytotoxicity of 20-65 microg/ml
      alachlor and 10-65 microg/ml acetochlor was significantly decreased by the
      addition of 10 microM RESV in Vero ER- cells whereas no significant change was
      detected on ER+ cell lines MCF-7 and HepG2. These results show that RESV protects
      non-transformed ER- cells, but has no such effect on ER+ tumor cells.

PMID- 15971861
TI  - Assessing child time-activity patterns in relation to indoor cooking fires in
      developing countries: a methodological comparison.
AB  - Indoor air pollution, caused by the indoor burning of biomass fuels, has been
      associated with an increased risk of child acute respiratory infections in
      developing countries. The amount of time that children spend in proximity to
      fires is a crucial determinant of the health impact of indoor air pollution.
      Researchers are reliant on social scientific methods to assess exposure based on
      child location patterns in relation to indoor fires. The inappropriate use of
      methods could lead to misclassification of exposure. The aim of this paper is to
      compare two methods (observations and questionnaire interview) with video
      analysis (which is thought to offer a more accurate assessment of exposure) in
      rural South African villages. Compared to video analysis, results show that
      observations may underestimate the amount of time that children spend very close
      (within 1.5 m) to fires. This is possibly due to reactivity caused by the
      presence of an observer. The questionnaire interview offers a more accurate
      assessment of the amounts of time that children spend within 1.5 m of fires at
      the expense of a detailed behavioural analysis. By drawing on the strengths and
      weaknesses of each, this paper discusses the appropriateness of methods to
      different research contexts.

PMID- 15971862
TI  - Saliva cortisol--a new approach in noise research to study stress effects.
AB  - Several studies have indicated an association between noise exposure and
      cardiovascular disease. A noise-induced release of stress hormones has been
      considered to be a biological pathway of importance in this respect. The
      described method is of special interest since concentration of cortisol in saliva
      reflects the concentration of free cortisol in serum and repeated saliva samples
      can easily be collected. Our objective is to overview the use of saliva cortisol
      to measure stress in relation to noise as a tool for research on noise-related
      cardiovascular risk. Previous studies of saliva cortisol in relation to noise
      exposure are reviewed. In summary, repeated assessments of saliva cortisol seems
      to be a feasible method to apply in field studies in noise research.

PMID- 15971863
TI  - Spirometry in primary care: in need of development.

PMID- 15971864
TI  - More public education needed on organ donation.

PMID- 15971867
TI  - Barts and The London NHS Trust. Creating a capital service for patients.
AB  - Nurses at Barts and The London NHS Trust play a key part in initiatives such as a
      Patient at Risk team, shared governance, Smarten Up and a host of other
      initiatives to improve the patient experience and working life for staff.

PMID- 15971868
TI  - Raising the standard: improving quality.

PMID- 15971869
TI  - Getting all hands to the practice stations.
AB  - Following the development of a clinical skills practical room, Rotherham General
      Hospital NHS Trust realised that it needed to have a more robust system of
      training staff. It was crucial to not only have the right equipment but also to
      have appropriately skilled people to run training sessions. As a result, the
      trust set up a post to organise training and the clinical skills facilitator has
      the remit to work across professional boundaries, providing support to nursing
      and medical staff and students. Karen Shaw offers an insight into her working
      week.

PMID- 15971870
TI  - Making a support group work for patients.
AB  - Patients need support to help cope with the effects of a gynaecological cancer
      diagnosis and treatment. The challenge is to meet their varied needs. Alison
      Griffiths discusses setting up a professionally led support group.

PMID- 15971871
TI  - What does it take to ensure effective hand decontamination by nurses?
AB  - John Camm describes a range of initiatives targeted at increasing awareness about
      the causes of hospital-acquired infection and promoting greater staff compliance
      with effective hand hygiene. The campaigns involve encouraging patients to raise
      concerns with nurses and installing handwashing facilities next to each patient's
      bed

PMID- 15971872
TI  - A guide to managing the surrounding skin of chronic, exuding wounds.
AB  - Preserving the skin's integrity is one of the primary jobs of the nurse and this
      is often a complex and difficult task, especially in the case of chronic wounds.
      This article identifies the factors associated with chronic wounds that can
      affect the surrounding skin and offer advice on the management and maintenance of
      skin integrity.

PMID- 15971873
TI  - Care of patients with heart failure and the use of ventricular assist devices.
AB  - Heart failure is becoming increasingly common as the population ages. Ventricular
      assist devices are used as a bridge for patients whose heart failure can no
      longer be controlled by medication and require a heart transplant. This article
      examines the care, rehabilitation and education of these patients.

PMID- 15971874
TI  - A long wait: how nurses can help patients through the transplantation pathway.
AB  - Heart transplants are a proven effective therapy for selected patients with end
      stage congestive heart failure. But selecting patients, waiting, receiving and
      recovery can be a long and anxious process. This article provides an overview of
      heart transplantation and the nurse's role in helping the patient during this
      time.

PMID- 15971875
TI  - Choosing a urinary catheter for short and long-term use.
AB  - There are many reasons why patients need a catheter, and the length of time one
      is needed varies, depending on the condition and how well the patient is. This
      review looks at the range of catheters available and the advantages and
      disadvantages for individual patients of the different sorts.

PMID- 15971876
TI  - Equipment and training are central to care.

PMID- 15971877
TI  - The process of devising and undertaking a trial to evaluate oxygen therapy
      products.
AB  - Streamlining the use of oxygen therapy products across a single trust has the
      merits of removing the need to switch equipment as patients are moved from one
      area to another and reducing the confusion faced by staff having to use similar,
      but different, products; it also improves patient care. The trial described
      incorporated all these strands.

PMID- 15971878
TI  - Laxatives.
AB  - Laxatives are used to treat constipation and to prepare the bowel before surgery
      or other investigative procedures. But, if used inappropriately, they can be
      dangerous, which can cause problems as many are sold over the counter. Carol
      McLoughlin looks at the types of laxative available, and how to help patients use
      them properly.

PMID- 15971879
TI  - 'Change is in the gift of people locally'. Interview by Carolyn Scott.

PMID- 15971880
TI  - How to write a business plan.

PMID- 15971881
TI  - Reaching into the teenage mind.

PMID- 15971882
TI  - [How to manage your patients before percutaneous renal biopsy].

PMID- 15971883
TI  - [How to search the appropriate puncture-site in the kidney and select the biopsy
      needles].

PMID- 15971884
TI  - [Immunosuppressive drug monitoring of cyclosporine, tacrolimus, and mycophenolate
      mofetil in renal transplantation].

PMID- 15971885
TI  - [The malignant tumor after renal transplantation].

PMID- 15971886
TI  - [Effects of intravascular contrast media on urinary excretion of liver fatty acid
      binding protein].
AB  - Proximal tubules of the kidney produce liver fatty acid-binding protein (L-FABP)
      and the level of messenger RNA is increased by physical and chemical stimuli. In
      this study, changes in urinary excretion of L-FABP were examined in 18 patients
      without renal dysfunction and who had undergone angiography using iodinated
      contrast media. On the day following angiography, the urinary excretion of L-FABP
      was markedly increased by 578 % (p<0.001) as compared with the value before the
      administration of contrast media. The urinary N-acetyl-beta-D-glucosaminidase
      excretion was also increased by +93%, however, the extent was less marked than
      for L-FABP. The urinary L-FABP excretion swiftly returned to the basal level on
      the second day after the angiography. No patient showed an increase in serum
      creatinine concentration, and the changes in urinary excretions of other
      microproteins, such as beta2-microglobulin and alpha1-microglobulin, were not
      significant. These results suggest that the urinary excretion of L-FABP
      sensitively reflects the injurious stress on renal tubules. Monitoring of urinary
      L-FABP may be useful in detecting the development of contrast media nephropathy
      at an early stage.

PMID- 15971887
TI  - [Case of primary antiphospholipid antibody syndrome with repeated renal
      biopsies].
AB  - Antiphospholipid antibody syndrome (APS) is characterized by the presence of
      repeated arterial and venous thrombosis, recurrent fetal loss and
      thrombocytopenia. Recently, renal involvement associated with APS is being
      increasingly recognized and discussed. In most cases, there has been a vascular
      nephropathy characterized by small vessel vaso-occulusive lesions associated with
      fibrous intimal hyperplasia of the interlobular arteries, thrombosis and focal
      cortical atrophy. We report a case of a 38-year-old patient with primary APS.
      Renal biopsies were performed three times in 26 years. Various glomerular and
      vascular lesions associated with APS were observed and discussed.

PMID- 15971888
TI  - [Interstitial pneumonia and nephritis with Sjogren's syndrome: successful
      treatment with corticosteroid therapy].
AB  - A Sixty eight-year-old man complained of shortness of breath on exercise since
      the spring of 2001. An abnormal lung shadow was pointed out on chest X-ray and
      progression of renal dysfunction and high gamma globulinemia were detected out on
      blood examination. He was admitted to the Department of Respiratory Disease in
      our hospital in March 2003, because of bilateral lower lung interstitial shadow,
      severe anemia (Hb 7.9 g/dl), and renal dysfunction (S-Cr 1.9 mg/dl). He was found
      to have hypergammaglobulinemia (IgG 2,997 mg/dl), positive RO/SS-A antigen, high
      serum KL-6 level (2,050 U/ml), and increased urinary excretion of beta2
      microglobulin (beta2MG). Both Gum test and Schirmer test results were positive.
      Lip biopsy showed cell infiltration to the salivary glands and he was diagnosed
      as having Sjogren's syndrome. Renal biopsy showed diffuse interstitial cell
      infiltration and a Trans Bronchoscopic Lung Biopsy (TBLB) showed fibrotic
      thickness and lymphocyte infiltration in the alveolar septum. Accordingly, he was
      diagnosed as having Sjogren's syndrome complicated with both interstitial
      nephritis and interstitial pneumonitis. He was treated by high-dose
      corticosteroid therapy and anticoagulant heparin. His laboratory data showed that
      both serum KL-6 and urinary beta2MG were reduced. Chest CT showed remarkable
      improvement of the interstitial shadow. A second renal biopsy performed at ten
      weeks after the beginning of treatment showed remarkable improvement of the
      interstitial cell infiltration. This is a rare case of Sjogren's syndrome
      complicated with interstitial nephritis and interstitial pneumonitis, treated
      successfully with high-dose corticosteroid therapy. Both complications showed
      immediate improvement with high-dose corticosteroid therapy, suggesting that
      early steroid therapy is effective for both complications.

PMID- 15971889
TI  - [Case of autosomal dominant polycystic kidney disease presenting hepatic
      encephalopathy].
AB  - We report a 71-year-old woman with autosomal dominant polycystic kidney disease
      (ADPKD), who presented with hepatic encephalopathy. She was diagnosed as having
      ADPKD at 61 years of age. Thereafter, her renal function gradually worsened and
      she was admitted to our hospital because of encephalopathy and end-stage renal
      failure. The main laboratory findings were as follows: BUN 77 mg/dl; creatinine
      9.0 mg/d; ammonia 573 microg/dl. Hepatic encephalopathy was improved after
      hemodialysis and administration of lactulose. The liver demonstrated multiple
      cysts on computed tomography. Angiography demonstrated that the peripheral branch
      of the portal vein was stenotic and a spleno-renal shunt was detected. We
      considered that portal hypertension was caused by multiple liver cysts, and that
      hepatic encephalopathy was caused by the spleno-renal shunt. It is generally
      considered that severe hepatic complications are rare in ADPKD, but this case
      suggested the need to screen for the development of hepatic lesions in ADPKD.

PMID- 15971890
TI  - [Case of autosomal dominant polycystic kidney disease associated with congenital
      hepatic fibrosis].
AB  - A 31-year-old man was admitted to the hospital because of a low-grade fever,
      general malaise, nausea, vomiting, and a poor appetite. On admission his renal
      function was severely deteriorated (serum creatinine 16.12 mg/dl, BUN 163 mg/dl),
      and he had severe anemia (Hb 7.5 g/dl) and thrombocytopenia (67,000/microl). A
      radiological examination revealed the presence of multiple cysts in his kidneys
      bilaterally. The patient was diagnosed as having end-stage renal disease due to
      polycystic kidney disease, and hemodialysis was started on the day of admission.
      After the initiation of hemodialysis, his symptoms and laboratory tests improved,
      except for anemia and thrombocytopenia. He was noted to have marked splenomegaly
      and dilation of the portal vein, raising the suspicion of portal hypertension as
      the cause of the splenomegaly and pancytopenia. To treat his pancytopenia (anemia
      and thrombocytopenia) and to determine the reason for his portal hypertension, a
      splenectomy and open-wedge biopsy of the liver were performed. Histological
      findings in the liver included extensive fibrosis of the portal areas with an
      excess of moderately dilated bile ducts, compatible with a diagnosis of
      congenital hepatic fibrosis. After splenectomy, his red blood cell and platelet
      counts returned to normal, and he was discharged on maintenance dialysis.
      Congenital hepatic fibrosis is often associated with autosomal recessive
      polycystic kidney disease (ARPKD), but not with autosomal dominant polycystic
      kidney disease (ADPKD). However, both his mother and older brother had multiple
      renal cysts, indicating that this was an unusual case of ADPKD complicated by
      congenital hepatic fibrosis.

PMID- 15971891
TI  - [Case of thrombotic thrombocytopenic purpura with a positive Coomb test].
AB  - We report a case of thrombotic thrombocytopenic purpura (TTP) with a positive
      Coombs' test. A 59-year-old female was admitted to our hospital in February, 1997
      with symptoms of heart failure. Ultrasound cardiography showed moderate
      pericardiac effusion and she was diagnosed as having pericarditis. After
      admission she had anorexia and her urine volume was reduced. Laboratory tests
      showed anemia and thrombocytopenia. Her Coombs' test result was positive. Her
      renal function gradually worsened and her conscious level was reduced. We
      diagnosed her as TTP and judged that she needed hemodialysis. We performed plasma
      exchange and started steroid therapy. The renal biopsy was compatible with TTP.
      After treatment, her level of consciousness improved, but her renal function did
      not improve. On the 51st hospital day she fell into acute respiratory distress
      syndrome (ARDS) and entered ICU. We considered ARDS caused by infection and
      continued treatment, but she died of shock and lactate acidosis. Activity of von
      Willebrand factor-cleaving protease in our case was 15% before the first PE, and
      25 % just before death. A case of TTP without collagen disease usually shows a
      negative Coombs' test result. We think that this was a rare case in which
      autoimmune hemolytic anemia was supervened with TTP.

PMID- 15971892
TI  - [Case of traditional herbal medicine-induced aristolochic acid nephropathy
      developing to end-stage renal failure].
AB  - A 48-year-old male was referred to our university hospital for severe azotemia
      with muscle cramp. He had been taking Chinese herbs as a traditional medicine to
      reduce hyperuricemia for about 9 months. Urinalysis showed trace proteinuria and
      hematuria without any casts. Renal glucosuria was also observed. In addition to
      azotemia, hyperchloremic metabolic acidosis and severe anemia were revealed.
      Hemodialysis was conducted and his general condition improved. A renal biopsy
      specimen revealed severe interstitial fibrosis and tubular atrophy with cellular
      degeneration. No remarkable glomerular changes were observed except for wrinkling
      of the basement membrane in a few glomeruli. Aristolochic acid was detected in
      the Chinese herbs, leading to the diagnosis of aristolochic acid nephropathy
      (AAN). His renal dysfunction was considered to be irreversible and he underwent
      maintenance hemodialysis. In Japan, AAN or Chinese herbs nephropathy decreased
      after an outbreak from 1995 to 2000. The public should be warned again that
      Chinese herbs, which are not permitted by the Japanese government, may contain
      aristolochic acid.

PMID- 15971893
TI  - On potentiality and respect for embryos: a reply to Mary Mahowald.
AB  - In order to understand the nature of human embryos I first distinguish between
      active and passive potentiality, and then argue that the former is found in human
      gametes and embryos (even in embryos in vitro that may fail to be implanted)
      because they all have an indwelling power or capacity to initiate certain
      changes. Implantation provides necessary conditions for the actualization of that
      prior, active potentiality. This does not imply that embryos are potential
      persons that do not deserve the same respect as actual persons. To claim that
      embryos "become persons" is to understand the predicate "person" as a phase
      sortal, roughly equivalent to "adult person." This entails that we would not be
      essentially persons. In order to explain the traditional understanding of
      "person" as a proper sortal rather than a phase sortal, the author distinguishes
      between proximate and remote potentiality, and shows that, unlike feline embryos,
      human embryos, by their genetic constitution, possess the remote potentiality to
      later exercise the typically human activities. It follows that they are already
      persons essentially.

PMID- 15971894
TI  - Sorting out the concept 'disorder'.
AB  - Current debates concerning the concept of mental disorder involve many different
      philosophical issues. However, it is not always clear from these discussions how,
      or whether, these issues relate to one another, or in exactly what way they are
      important for the definition of disorder. This article aims to sort through some
      of the philosophical issues that arise in the current literature and provide a
      clarification of how these issues are related to one another and whether they are
      necessary for defining disorder. I argue that the main concern in defining
      disorder, namely demarcation, is obscured by a number of these other
      philosophical issues and that a focus on demarcation gives us a means of placing
      these other issues in a clarifying context.

PMID- 15971895
TI  - Identity and moral responsibility of healthcare organizations.
AB  - In this paper the moral responsibility of a Healthcare Organization (HCO) is
      conceived as an inextricable aspect of the identity of the HCO. We attempt to
      show that by exploring this relation a more profound insight in moral
      responsibility can be gained. Referring to Charles Taylor we explore the meaning
      of the concept of identity. It consists of three interdependent dimensions: a
      moral, a dialogical, and a narrative one. In section two we develop some
      additional arguments to apply his concept of personal identity to organizations.
      The final section works out the relationship of three dimensions of identity to
      some actual issues in contemporary HCOs: the tension between care and justice,
      the importance of dialogues about the diversity of goods, and the relevance of
      becoming familiar with the life-story of the HCO. Identity of an HCO is
      established and developed in commitments to and identification with certain goods
      that are central for a HCO. However, many of these goods are interwoven with
      everyday practices and policies. Therefore, moral responsibility asks for
      articulation of goods that often stay implicit and should not be reduced to a
      merely procedural approach. However difficult this articulation may be, if it is
      not tried at all HCOs run the risk of drifting away from their very identity as
      healthcare institutions: to offer care to patients and to do this in accordance
      with demands of social justice.

PMID- 15971896
TI  - Neurological diseases of the Cavalier King Charles spaniel.
AB  - Several neurological syndromes have been described in Cavalier King Charles
      spaniels and many of the conditions have similar clinical signs. The current
      knowledge of these syndromes is reviewed in this article, with the aim of
      enabling the general practitioner to formulate a differential diagnosis and plan
      for diagnostic tests and treatment. Specifically, the article discusses and
      contrasts the most common conditions seen, Including occipital
      hypoplasia/syringomyelia, episodic collapse, epilepsy and vestibular disorders.

PMID- 15971897
TI  - Prevalence of gastrointestinal tract lesions in 73 brachycephalic dogs with upper
      respiratory syndrome.
AB  - OBJECTIVES: To determine the prevalence of gastrointestinal tract lesions in
      brachycephalic dogs with upper respiratory tract disease. METHODS: The
      gastrointestinal tract and respiratory disorders of 73 brachycephalic dogs
      presented with upper respiratory signs were evaluated. Clinical signs and
      endoscopic and histological anomalies of the upper digestive tract were analysed.
      RESULTS: A very high prevalence of gastrointestinal tract problems in
      brachycephalic dogs presented with upper respiratory problems was observed
      clinically, endoscopically and histologically. Endoscopic anomalies of the upper
      digestive tract were present even in dogs without digestive clinical signs.
      Furthermore, histological evaluation of the digestive tract sometimes showed
      inflammatory lesions not macroscopically visible at endoscopy. Statistical
      analysis showed a relationship between the severity of the respiratory and
      digestive signs. This was significant in French bulldogs, males and heavy
      brachycephalic dogs. CLINICAL SIGNIFICANCE: These observations show a correlation
      between upper respiratory and gastrointestinal tract problems in brachycephalic
      breeds with upper respiratory disease. Surgical treatment of respiratory disease
      could improve the digestive clinical signs, and/or gastro-oesophageal medical
      treatment could improve the outcome for surgically treated brachycephalic dogs.

PMID- 15971898
TI  - Computed tomography as an aid in the diagnosis of chronic nasal disease in dogs.
AB  - OBJECTIVES: To assess the use of computed tomography (CT) in the diagnosis of
      chronic nasal disease in dogs. METHODS: A retrospective study of 85 dogs with
      chronic nasal discharge due to primary nasal disease, which had undergone nasal
      CT and biopsy, was carried out. Medical records were reviewed for signalment,
      clinical signs, CT findings, endoscopic findings and histopathology. The results
      obtained via CT were correlated with nasal histopathology and gross anatomical
      observations were recorded at the time of rhinoscopy. RESULTS: Neoplasia was
      diagnosed in 37 dogs for which CT typically revealed a soft tissue density
      associated with extensive turbinate destruction. Inflammatory rhinitis was
      diagnosed in 40 dogs. CT disclosed either normal turbinate structures or mild to
      moderate turbinate destruction, with or without the presence of soft tissue
      densities (mucopus) within the nasal passages. Fungal rhinitis was diagnosed in
      seven dogs for which CT disclosed extensive turbinate destruction with
      hyperlucency of the nasal passages. One dog had normal CT and histopathology
      findings. CLINICAL SIGNIFICANCE: CT greatly enhanced the ability to diagnose
      chronic nasal disease in dogs, providing detailed Information regarding the
      extent of the disease, accurate discrimination of neoplastic versus non
      neoplastic diseases, and identification of areas of the nose to examine
      rhinoscopically and suspicious regions to target for biopsy.

PMID- 15971899
TI  - Small-cell carcinoma of the lung resembling a brachial plexus tumour.
AB  - A small-cell carcinoma of the lung was identified in a six-year-old female German
      shepherd dog with a history of chronic lameness of the left forelimb, Horner's
      syndrome and sensory deficits on the caudal portion of the left forelimb below
      the elbow. A mass, the exact location of which was difficult to ascertain, was
      identified during radiographic examination of the thorax. It was easily
      identified, using magnetic resonance imaging, as an apical tumour of the left
      lung with dorsal extension and involvement of paraspinal structures, such as
      spinal nerve roots C8 to T1 and the sympathetic trunk. Postmortem examination
      confirmed a mass in the left apical lobe of the lung, compatible with a diagnosis
      of small-cell carcinoma by histopathology and immunohistochemistry. This clinical
      presentation is similar to Pancoast syndrome described in humans.

PMID- 15971900
TI  - Cerebellar cortical degeneration in three English bulldogs: clinical and
      neuropathological findings.
AB  - This case report describes the clinical and neuropathological findings in three
      young English bulldogs affected by cerebellar cortical degeneration. The dogs,
      born from the same parents, were presented with clinical signs indicating
      progressive cerebellar dysfunction: a wide-based stance, severe cerebellar ataxia
      characterised by marked hypermetria, spasticity, and intention tremors of the
      head and trunk with loss of balance. On histopathological examination, lesions
      were confined to the cerebellum and consisted of diffuse degenerative cortical
      lesions, and there was a loss of Purkinje and granule cells. The history,
      clinical signs and neuropathological findings confirmed the diagnosis of
      cerebellar cortical degeneration. To the authors' knowledge, this is the first
      report of cerebellar cortical degeneration in the English bulldog.

PMID- 15971901
TI  - Sensory neuropathy in two Border collie puppies.
AB  - A peripheral sensory neuropathy was diagnosed in two Border collie puppies.
      Neurological, electrophysiological and histopathological examinations suggested a
      purely sensory neuropathy with mainly distal involvement. Urinary incontinence
      was observed in one of the puppies and histological examination of the vagus
      nerve revealed degenerative changes. An inherited disorder was suspected.

PMID- 15971903
TI  - Bacterial infective arthritis: an uncommon condition?

PMID- 15971902
TI  - Anaplasma phagocytophilum infection in a dog: identifying the causative agent
      using PCR.
AB  - A diagnosis of Anaplasma phagocytophilum infection was confirmed in a two-year
      old male golden retriever displaying few clinical and haematological
      abnormalities. This was achieved by demonstrating ehrlichial organisms in
      circulating neutrophils, by indirect immunofluorescence assay using A
      phagocytophilum as an antigen, and by detecting DNA specific for the 16S rRNA
      gene of granulocytic Anaplasma by PCR. After treatment with doxycycline for 10
      days the dog showed improvement and the laboratory values returned to normal.

PMID- 15971905
TI  - Provision around the clock: new RCVS guidance on 24-hour cover.

PMID- 15971906
TI  - Training and living with an assistance dog.

PMID- 15971904
TI  - What is your diagnosis? Degenerative joint disease.

PMID- 15971907
TI  - Nurses: the pride of ownership.

PMID- 15971908
TI  - TNA designates first Nurse-Friendly Hospitals.

PMID- 15971910
TI  - Learning semantic scene models from observing activity in visual surveillance.
AB  - This paper considers the problem of automatically learning an activity-based
      semantic scene model from a stream of video data. A scene model is proposed that
      labels regions according to an identifiable activity in each region, such as
      entry/exit zones, junctions, paths, and stop zones. We present several
      unsupervised methods that learn these scene elements and present results that
      show the efficiency of our approach. Finally, we describe how the models can be
      used to support the interpretation of moving objects in a visual surveillance
      environment.

PMID- 15971911
TI  - Visual learning by coevolutionary feature synthesis.
AB  - In this paper, a novel genetically inspired visual learning method is proposed.
      Given the training raster images, this general approach induces a sophisticated
      feature-based recognition system. It employs the paradigm of cooperative
      coevolution to handle the computational difficulty of this task. To represent the
      feature extraction agents, the linear genetic programming is used. The paper
      describes the learning algorithm and provides a firm rationale for its design.
      Different architectures of recognition systems are considered that employ the
      proposed feature synthesis method. An extensive experimental evaluation on the
      demanding real-world task of object recognition in synthetic aperture radar (SAR)
      imagery shows the ability of the proposed approach to attain high recognition
      performance in different operating conditions.

PMID- 15971912
TI  - Evolutionary optimization of a hierarchical object recognition model.
AB  - A major problem in designing artificial neural networks is the proper choice of
      the network architecture. Especially for vision networks classifying three
      dimensional (3-D) objects this problem is very challenging, as these networks are
      necessarily large and therefore the search space for defining the needed networks
      is of a very high dimensionality. This strongly increases the chances of
      obtaining only suboptimal structures from standard optimization algorithms. We
      tackle this problem in two ways. First, we use biologically inspired hierarchical
      vision models to narrow the space of possible architectures and to reduce the
      dimensionality of the search space. Second, we employ evolutionary optimization
      techniques to determine optimal features and nonlinearities of the visual
      hierarchy. Here, we especially focus on higher order complex features in higher
      hierarchical stages. We compare two different approaches to perform an
      evolutionary optimization of these features. In the first setting, we directly
      code the features into the genome. In the second setting, in analogy to an
      ontogenetical development process, we suggest the new method of an indirect
      coding of the features via an unsupervised learning process, which is embedded
      into the evolutionary optimization. In both cases the processing nonlinearities
      are encoded directly into the genome and are thus subject to optimization. The
      fitness of the individuals for the evolutionary selection process is computed by
      measuring the network classification performance on a benchmark image database.
      Here, we use a nearest-neighbor classification approach, based on the
      hierarchical feature output. We compare the found solutions with respect to their
      ability to generalize. We differentiate between a first- and a second-order
      generalization. The first-order generalization denotes how well the vision
      system, after evolutionary optimization of the features and nonlinearities using
      a database A, can classify previously unseen test views of objects from this
      database A. As second-order generalization, we denote the ability of the vision
      system to perform classification on a database B using the features and
      nonlinearities optimized on database A. We show that the direct feature coding
      approach leads to networks with a better first-order generalization, whereas the
      second-order generalization is on an equally high level for both direct and
      indirect coding. We also compare the second-order generalization results with
      other state-of-the-art recognition systems and show that both approaches lead to
      optimized recognition systems, which are highly competitive with recent
      recognition algorithms.

PMID- 15971913
TI  - Visual learning by imitation with motor representations.
AB  - We propose a general architecture for action (mimicking) and program (gesture)
      level visual imitation. Action-level imitation involves two modules. The
      viewpoint Transformation (VPT) performs a "rotation" to align the demonstrator's
      body to that of the learner. The Visuo-Motor Map (VMM) maps this visual
      information to motor data. For program-level (gesture) imitation, there is an
      additional module that allows the system to recognize and generate its own
      interpretation of observed gestures to produce similar gestures/goals at a later
      stage. Besides the holistic approach to the problem, our approach differs from
      traditional work in i) the use of motor information for gesture recognition; ii)
      usage of context (e.g., object affordances) to focus the attention of the
      recognition system and reduce ambiguities, and iii) use iconic image
      representations for the hand, as opposed to fitting kinematic models to the video
      sequence. This approach is motivated by the finding of visuomotor neurons in the
      F5 area of the macaque brain that suggest that gesture recognition/imitation is
      performed in motor terms (mirror) and rely on the use of object affordances
      (canonical) to handle ambiguous actions. Our results show that this approach can
      outperform more conventional (e.g., pure visual) methods.

PMID- 15971914
TI  - Active concept learning in image databases.
AB  - Concept learning in content-based image retrieval systems is a challenging task.
      This paper presents an active concept learning approach based on the mixture
      model to deal with the two basic aspects of a database system: the changing
      (image insertion or removal) nature of a database and user queries. To achieve
      concept learning, we a) propose a new user directed semi-supervised expectation
      maximization algorithm for mixture parameter estimation, and b) develop a novel
      model selection method based on Bayesian analysis that evaluates the consistency
      of hypothesized models with the available information. The analysis of
      exploitation versus exploration in the search space helps to find the optimal
      model efficiently. Our concept knowledge transduction approach is able to deal
      with the cases of image insertion and query images being outside the database.
      The system handles the situation where users may mislabel images during relevance
      feedback. Experimental results on Corel database show the efficacy of our active
      concept learning approach and the improvement in retrieval performance by concept
      transduction.

PMID- 15971915
TI  - Face detection using spectral histograms and SVMs.
AB  - We present a face detection method using spectral histograms and support vector
      machines (SVMs). Each image window is represented by its spectral histogram,
      which is a feature vector consisting of histograms of filtered images. Using
      statistical sampling, we show systematically the representation groups face
      images together; in comparison, commonly used representations often do not
      exhibit this necessary and desirable property. By using an SVM trained on a set
      of 4500 face and 8000 nonface images, we obtain a robust classifying function for
      face and non-face patterns. With an effective illumination-correction algorithm,
      our system reliably discriminates face and nonface patterns in images under
      different kinds of conditions. Our method on two commonly used data sets give the
      best performance among recent face-detection ones. We attribute the high
      performance to the desirable properties of the spectral histogram representation
      and good generalization of SVMs. Several further improvements in computation time
      and in performance are discussed.

PMID- 15971916
TI  - Learning from examples in the small sample case: face expression recognition.
AB  - Example-based learning for computer vision can be difficult when a large number
      of examples to represent each pattern or object class is not available. In such
      situations, learning from a small number of samples is of practical value. To
      study this issue, the task of face expression recognition with a small number of
      training images of each expression is considered. A new technique based on linear
      programming for both feature selection and classifier training is introduced. A
      pairwise framework for feature selection, instead of using all classes
      simultaneously, is presented. Experimental results compare the method with three
      others: a simplified Bayes classifier, support vector machine, and AdaBoost.
      Finally, each algorithm is analyzed and a new categorization of these algorithms
      is given, especially for learning from examples in the small sample case.

PMID- 15971917
TI  - Kernel pooled local subspaces for classification.
AB  - We investigate the use of subspace analysis methods for learning low-dimensional
      representations for classification. We propose a kernel-pooled local discriminant
      subspace method and compare it against competing techniques: kernel principal
      component analysis (KPCA) and generalized discriminant analysis (GDA) in
      classification problems. We evaluate the classification performance of the
      nearest-neighbor rule with each subspace representation. The experimental results
      using several data sets demonstrate the effectiveness and performance superiority
      of the kernel-pooled subspace method over competing methods such as KPCA and GDA
      in some classification problems.

PMID- 15971918
TI  - Self-organizing maps for learning the edit costs in graph matching.
AB  - Although graph matching and graph edit distance computation have become areas of
      intensive research recently, the automatic inference of the cost of edit
      operations has remained an open problem. In the present paper, we address the
      issue of learning graph edit distance cost functions for numerically labeled
      graphs from a corpus of sample graphs. We propose a system of self-organizing
      maps (SOMs) that represent the distance measuring spaces of node and edge labels.
      Our learning process is based on the concept of self-organization. It adapts the
      edit costs in such a way that the similarity of graphs from the same class is
      increased, whereas the similarity of graphs from different classes decreases. The
      learning procedure is demonstrated on two different applications involving line
      drawing graphs and graphs representing diatoms, respectively.

PMID- 15971919
TI  - Self-organizing topological tree for online vector quantization and data
      clustering.
AB  - The self-organizing Maps (SOM) introduced by Kohonen implement two important
      operations: vector quantization (VQ) and a topology-preserving mapping. In this
      paper, an online self-organizing topological tree (SOTT) with faster learning is
      proposed. A new learning rule delivers the efficiency and topology preservation,
      which is superior of other structures of SOMs. The computational complexity of
      the proposed SOTT is O(log N) rather than O(N) as for the basic SOM. The
      experimental results demonstrate that the reconstruction performance of SOTT is
      comparable to the full-search SOM and its computation time is much shorter than
      the full-search SOM and other vector quantizers. In addition, SOTT delivers the
      hierarchical mapping of codevectors and the progressive transmission and decoding
      property, which are rarely supported by other vector quantizers at the same time.
      To circumvent the shortcomings of clustering performance of classical partition
      clustering algorithms, a hybrid clustering algorithm that fully exploit the
      online learning and multiresolution characteristics of SOTT is devised. A new
      linkage metric is proposed which can be updated online to accelerate the time
      consuming agglomerative hierarchical clustering stage. Besides the enhanced
      clustering performance, due to the online learning capability, the memory
      requirement of the proposed SOTT hybrid clustering algorithm is independent of
      the size of the data set, making it attractive for large database.

PMID- 15971920
TI  - A learning-based method for image super-resolution from zoomed observations.
AB  - We propose a technique for super-resolution imaging of a scene from observations
      at different camera zooms. Given a sequence of images with different zoom factors
      of a static scene, we obtain a picture of the entire scene at a resolution
      corresponding to the most zoomed observation. The high-resolution image is
      modeled through appropriate parameterization, and the parameters are learned from
      the most zoomed observation. Assuming a homogeneity of the high-resolution field,
      the learned model is used as a prior while super-resolving the scene. We suggest
      the use of either a Markov random field (MRF) or an simultaneous autoregressive
      (SAR) model to parameterize the field based on the computation one can afford. We
      substantiate the suitability of the proposed method through a large number of
      experimentations on both simulated and real data.

PMID- 15971921
TI  - Object detection via feature synthesis using MDL-based genetic programming.
AB  - In this paper, we use genetic programming (GP) to synthesize composite operators
      and composite features from combinations of primitive operations and primitive
      features for object detection. The motivation for using GP is to overcome the
      human experts' limitations of focusing only on conventional combinations of
      primitive image processing operations in the feature synthesis. GP attempts many
      unconventional combinations that in some cases yield exceptionally good results.
      To improve the efficiency of GP and prevent its well-known code bloat problem
      without imposing severe restriction on the GP search, we design a new fitness
      function based on minimum description length principle to incorporate both the
      pixel labeling error and the size of a composite operator into the fitness
      evaluation process. To further improve the efficiency of GP, smart crossover,
      smart mutation and a public library ideas are incorporated to identify and keep
      the effective components of composite operators. Our experiments, which are
      performed on selected training regions of a training image to reduce the training
      time, show that compared to normal GP, our GP algorithm finds effective composite
      operators more quickly and the learned composite operators can be applied to the
      whole training image and other similar testing images. Also, compared to a
      traditional region-of-interest extraction algorithm, the composite operators
      learned by GP are more effective and efficient for object detection.

PMID- 15971922
TI  - Evolving binary classifiers through parallel computation of multiple fitness
      cases.
AB  - This paper describes two versions of a novel approach to developing binary
      classifiers, based on two evolutionary computation paradigms: cellular
      programming and genetic programming. Such an approach achieves high computation
      efficiency both during evolution and at runtime. Evolution speed is optimized by
      allowing multiple solutions to be computed in parallel. Runtime performance is
      optimized explicitly using parallel computation in the case of cellular
      programming or implicitly taking advantage of the intrinsic parallelism of
      bitwise operators on standard sequential architectures in the case of genetic
      programming. The approach was tested on a digit recognition problem and compared
      with a reference classifier.

PMID- 15971923
TI  - A criterion for optimizing kernel parameters in KBDA for image retrieval.
AB  - A criterion is proposed to optimize the kernel parameters in Kernel-based Biased
      Discriminant Analysis (KBDA) for image retrieval. Kernel parameter optimization
      is performed by optimizing the kernel space such that the positive images are
      well clustered while the negative ones are pushed far away from the positives.
      The proposed criterion measures the goodness of a kernel space, and the optimal
      kernel parameter set is obtained by maximizing this criterion. Retrieval
      experiments on two benchmark image databases demonstrate the effectiveness of
      proposed criterion for KBDA to achieve the best possible performance at the cost
      of a small fractional computational overhead.

PMID- 15971924
TI  - Image transform bootstrapping and its applications to semantic scene
      classification.
AB  - The performance of an exemplar-based scene classification system depends largely
      on the size and quality of its set of training exemplars, which can be limited in
      practice. In addition, in nontrivial data sets, variations in scene content as
      well as distracting regions may exist in many testing images to prohibit good
      matches with the exemplars. Various boosting schemes have been proposed in
      machine learning, focusing on the feature space. We introduce the novel concept
      of image-transform bootstrapping using transforms in the image space to address
      such issues. In particular, three major schemes are described for exploiting this
      concept to augment training, testing, and both. We have successfully applied it
      to three applications of increasing difficulty: sunset detection, outdoor scene
      classification, and automatic image orientation detection. It is shown that
      appropriate transforms and meta-classification methods can be selected to boost
      performance according to the domain of the problem and the features/classifier
      used.

PMID- 15971925
TI  - EM in high-dimensional spaces.
AB  - This paper considers fitting a mixture of Gaussians model to high-dimensional
      data in scenarios where there are fewer data samples than feature dimensions.
      Issues that arise when using principal component analysis (PCA) to represent
      Gaussian distributions inside Expectation-Maximization (EM) are addressed, and a
      practical algorithm results. Unlike other algorithms that have been proposed,
      this algorithm does not try to compress the data to fit low-dimensional models.
      Instead, it models Gaussian distributions in the (N - 1)-dimensional space
      spanned by the N data samples. We are able to show that this algorithm converges
      on data sets where low-dimensional techniques do not.

PMID- 15971926
TI  - Robust fusion of uncertain information.
AB  - A technique is presented to combine n data points, each available with point
      dependent uncertainty, when only a subset of these points come from N < n
      sources, where N is unknown. We detect the significant modes of the underlying
      multivariate probability distribution using a generalization of the nonparametric
      mean shift procedure. The number of detected modes automatically defines N, while
      the belonging of a point to the basin of attraction of a mode provides the fusion
      rule. The robust data fusion algorithm was successfully applied to two computer
      vision problems: estimating the multiple affine transformations, and range image
      segmentation.

PMID- 15971927
TI  - Recursive three-dimensional model reconstruction based on Kalman filtering.
AB  - A recursive two-step method to recover structure and motion from image sequences
      based on Kalman filtering is described in this paper. The algorithm consists of
      two major steps. The first step is an extended Kalman filter (EKF) for the
      estimation of the object's pose. The second step is a set of EKFs, one for each
      model point, for the refinement of the positions of the model features in the
      three-dimensional (3-D) space. These two steps alternate from frame to frame. The
      initial model converges to the final structure as the image sequence is scanned
      sequentially. The performance of the algorithm is demonstrated with both
      synthetic data and real-world objects. Analytical and empirical comparisons are
      made among our approach, the interleaved bundle adjustment method, and the Kalman
      filtering-based recursive algorithm by Azarbayejani and Pentland. Our approach
      outperformed the other two algorithms in terms of computation speed without loss
      in the quality of model reconstruction.

PMID- 15971928
TI  - A kernel autoassociator approach to pattern classification.
AB  - Autoassociators are a special type of neural networks which, by learning to
      reproduce a given set of patterns, grasp the underlying concept that is useful
      for pattern classification. In this paper, we present a novel nonlinear model
      referred to as kernel autoassociators based on kernel methods. While conventional
      non-linear autoassociation models emphasize searching for the non-linear
      representations of input patterns, a kernel autoassociator takes a kernel feature
      space as the nonlinear manifold, and places emphasis on the reconstruction of
      input patterns from the kernel feature space. Two methods are proposed to address
      the reconstruction problem, using linear and multivariate polynomial functions,
      respectively. We apply the proposed model to novelty detection with or without
      novelty examples and study it on the promoter detection and sonar target
      recognition problems. We also apply the model to mclass classification problems
      including wine recognition, glass recognition, handwritten digit recognition, and
      face recognition. The experimental results show that, compared with conventional
      autoassociators and other recognition systems, kernel autoassociators can provide
      better or comparable performance for concept learning and recognition in various
      domains.

PMID- 15971929
TI  - Eliminating false matches for the projective registration of free-form surfaces
      with small translational motions.
AB  - In this paper, we make a detailed study of two rigid-motion constraints. The
      importance of these two constraints is twofold: first, they reveal the inherent
      relationship between the three-dimensional-two-dimensional (3-D-2-D) point
      correspondences and the motion parameters of interest; second, they can be used
      to measure the traditional ICP criterion established point match qualities based
      on which different point matches can be compared and relatively good point
      matches can be selected for motion-parameter update in the projective
      registration of free-form surfaces subject to small translational motions. The
      experimental results based on both synthetic data and real images have shown that
      the rigid motion constraints are powerful in evaluating the possible 3-D-2-D
      point matches established by the traditional ICP criterion, thus achieving
      encouraging projective registration results.

PMID- 15971930
TI  - Sample-sort simulated annealing.
AB  - A simulated annealing (SA) algorithm called Sample-Sort that is artificially
      extended across an array of samplers is proposed. The sequence of temperatures
      for a serial SA algorithm is replaced with an array of samplers operating at
      static temperatures and the single stochastic sampler is replaced with a set of
      samplers. The set of samplers uses a biased generator to sample the same
      distribution of a serial SA algorithm to maintain the same convergence property.
      Sample-Sort was compared to SA by applying both to a set of global optimization
      problems and found to be comparable if the number of iterations per sampler was
      sufficient. If the evaluation phase dominates the computational requirements,
      Sample-Sort could take advantage of parallel processing.

PMID- 15971931
TI  - Genetically optimized fuzzy decision trees.
AB  - In this study, we are concerned with genetically optimized fuzzy decision trees
      (G-DTs). Decision trees are fundamental architectures of machine learning,
      pattern recognition, and system modeling. Starting with the generic decision tree
      with discrete or interval-valued attributes, we develop its fuzzy set-based
      generalization. In this generalized structure we admit the values of the
      attributes that are represented by some membership functions. Such fuzzy decision
      trees are constructed in the setting of genetic optimization. The underlying
      genetic algorithm optimizes the parameters of the fuzzy sets associated with the
      individual nodes where they play a role of fuzzy "switches" by distributing a
      flow of processing completed within the tree. We discuss various forms of the
      fitness function that help capture the essence of the problem at hand (that could
      be either of classification nature when dealing with discrete outputs or
      regression-like when handling a continuous output variable). We quantify a nature
      of the generalization of the tree by studying an optimally adjusted spreads of
      the membership functions located at the nodes of the decision tree. A series of
      experiments exploiting synthetic and machine learning data is used to illustrate
      the performance of the G-DTs.

PMID- 15971932
TI  - UVR, vitamin D and three autoimmune diseases--multiple sclerosis, type 1
      diabetes, rheumatoid arthritis.
AB  - We review the evidence indicating a possible beneficial role for UVR on three Th1
      mediated autoimmune diseases: multiple sclerosis, type 1 diabetes and rheumatoid
      arthritis in relation to recent developments in photoimmunology. Recent work
      suggests that UVR exposure may be one factor that can attenuate the autoimmune
      activity leading to these three diseases through several pathways involving UVB
      and UVA irradiation, UVR-derived vitamin D synthesis and other routes such as
      alpha-melanocyte-stimulating hormone, calcitonin gene related peptide and
      melatonin. Ecological features, particularly a gradient of increasing prevalence
      of multiple sclerosis and type 1 diabetes with higher latitude, provide some
      support for a beneficial role of UVR. Analytical studies provide additional
      support, particularly as low vitamin D has been prospectively associated with
      disease onset for all three diseases, but are not definitive. Randomized
      controlled trial data are required. Further, we discuss how associated genetic
      studies may assist the accumulation of evidence with regard to the possible
      causal role of low UVR exposure and/or low vitamin D status in the development of
      these diseases.

PMID- 15971933
TI  - Temporally and spatially heterogeneous distribution of mTHPC in a murine tumor
      observed by two-color confocal fluorescence imaging and spectroscopy in a whole
      mount model.
AB  - Efficient intratumor delivery of anticancer drugs and photosensitizers is an
      important factor in the success of chemotherapy and photodynamic therapy,
      respectively. Unfortunately, their adequate and uniform intratumor distribution
      is impeded by several physiological barriers and by binding to tissue components.
      Measurement of gross tumor drug accumulation is a routine method of investigating
      the uptake and clearance of chemotherapy agents and photosensitizers but tells
      little about their extravascular spatial distribution. We use whole-mount two
      color confocal fluorescence imaging and imaging spectroscopy of unprocessed
      excised murine tumor fragments to investigate the intratumor distribution of the
      photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC) as a function of distance
      from blood vessels perfused with 0.2 mum diameter fluorescent microspheres.
      Significant mismatches between drug and perfused vasculature are caused by
      heterogeneities in tumor blood supply. We describe complex microscopic mTHPC
      gradients that reverse dramatically relative to the perfused vasculature with
      time after injection. This imaging technique can be applied to screen the dynamic
      intratumor distribution of other fluorescent photosensitizers and anticancer
      drugs.

PMID- 15971934
TI  - Medical decision making: the family-doctor-patient triad.

PMID- 15971935
TI  - Hooray for hypoxia?

PMID- 15971936
TI  - Tinnitus perception and distress is related to abnormal spontaneous brain
      activity as measured by magnetoencephalography.
AB  - BACKGROUND: The neurophysiological mechanisms underlying tinnitus perception are
      not well understood. Surprisingly, there have been no group studies comparing
      abnormalities in ongoing, spontaneous neuronal activity in individuals with and
      without tinnitus perception. METHODS AND FINDINGS: Here, we show that the
      spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is
      characterised by a marked reduction in alpha (8-12 Hz) power together with an
      enhancement in delta (1.5-4 Hz) as compared to a normal hearing control group (n
      = 16). This pattern was especially pronounced for temporal regions. Moreover,
      correlations with tinnitus-related distress revealed strong associations with
      this abnormal spontaneous activity pattern, particularly in right temporal and
      left frontal areas. Overall, effects were stronger for the alpha than for the
      delta frequency band. A data stream of 5 min, recorded with a whole-head
      neuromagnetometer under a resting condition, was sufficient to extract the marked
      differences. CONCLUSIONS: Despite some limitations, there are arguments that the
      regional pattern of abnormal spontaneous activity we found could reflect a
      tinnitus-related cortical network. This finding, which suggests that a
      neurofeedback approach could reduce the adverse effects of this disturbing
      condition, could have important implications for the treatment of tinnitus.

PMID- 15971937
TI  - A 61-year-old man with dyspepsia and weight loss.

PMID- 15971938
TI  - Allocating antiretrovirals in South Africa: using modeling to determine treatment
      equity.

PMID- 15971939
TI  - Malaria diagnosis and treatment: one size does not fit all.

PMID- 15971940
TI  - The debate over placebo-controlled trials.

PMID- 15971941
TI  - Derivation of multipotent mesenchymal precursors from human embryonic stem cells.
AB  - BACKGROUND: Human embryonic stem cells provide access to the earliest stages of
      human development and may serve as a source of specialized cells for regenerative
      medicine. Thus, it becomes crucial to develop protocols for the directed
      differentiation of embryonic stem cells into tissue-restricted precursors.
      METHODS AND FINDINGS: Here, we present culture conditions for the derivation of
      unlimited numbers of pure mesenchymal precursors from human embryonic stem cells
      and demonstrate multilineage differentiation into fat, cartilage, bone, and
      skeletal muscle cells. CONCLUSION: Our findings will help to elucidate the
      mechanism of mesoderm specification during embryonic stem cell differentiation
      and provide a platform to efficiently generate specialized human mesenchymal cell
      types for future clinical applications.

PMID- 15971944
TI  - Vitamin C for preventing and treating the common cold.

PMID- 15971943
TI  - Treating critical illness: the importance of first doing no harm.

PMID- 15971945
TI  - How the Cochrane collaboration is responding to the Asian tsunami.

PMID- 15971946
TI  - Intention to lose weight, weight changes, and 18-y mortality in overweight
      individuals without co-morbidities.
AB  - BACKGROUND: Weight loss in the obese improves risk factors for cardiovascular
      diseases and diabetes. However, several studies have shown inconsistent long-term
      effects of weight loss on mortality. We investigated the influence on mortality
      of intention to lose weight and subsequent weight changes among overweight
      individuals without known co-morbidities. METHODS AND FINDINGS: In 1975, a cohort
      of individuals reported height, weight, and current attempts (defined as
      "intention") to lose weight, and in 1981, they reported current weight. Mortality
      of the 2,957 participants with body mass index > or = 25 kg/m2 in 1975 and
      without pre-existing or current diseases was followed from 1982 through 1999, and
      268 participants died. The association of intention to lose weight in 1975 and
      actual weight change until 1981 with mortality was analysed while controlling for
      behavioural and psychosocial risk factors and hypertension as possible
      confounders. Compared with the group not intending to lose and able to maintain
      stable weight, the hazard ratios (with 95% confidence intervals) in the group
      intending to lose weight were 0.84 (0.49-1.48) for those with stable weight, 1.86
      (1.22-2.87) for those losing weight, and 0.93 (0.55-1.56) for those gaining
      weight. In the group not intending to lose weight, hazard ratios were 1.17 (0.82
      1.66) for those who did lose weight, and 1.57 (1.08-2.30) for those gaining
      weight. CONCLUSION: Deliberate weight loss in overweight individuals without
      known co-morbidities may be hazardous in the long term. The health effects of
      weight loss are complex, possibly composed of oppositely acting processes, and
      need more research.

PMID- 15971948
TI  - Meeting the health needs of migrant workers affected by the tsunami.

PMID- 15971949
TI  - Should health professionals allow reporters inside hospitals and clinics at times
      of natural disasters?

PMID- 15971947
TI  - High risk of unexpected late fetal death in monochorionic twins despite intensive
      ultrasound surveillance: a cohort study.
AB  - BACKGROUND: The rationale for fetal surveillance in monochorionic twin
      pregnancies is timely intervention to prevent the increased fetal/perinatal
      morbidity and mortality attributed to twin-twin transfusion syndrome and
      intrauterine growth restriction. We investigated the residual risk of fetal death
      after viability in otherwise uncomplicated monochorionic diamniotic twin
      pregnancies. METHODS AND FINDINGS: We searched an electronic database of 480
      completed monochorionic pregnancies that underwent fortnightly ultrasound
      surveillance in our tertiary referral fetal medicine service between 1992 and
      2004. After excluding pregnancies with twin-twin transfusion syndrome, growth
      restriction, structural abnormalities, or twin reversed arterial perfusion
      sequence, and monoamniotic and high-order multiple pregnancies, we identified 151
      uncomplicated monochorionic diamniotic twin pregnancies with normal growth,
      normal liquor volume, and normal Doppler studies on fortnightly ultrasound scans.
      Ten unexpected intrauterine deaths occurred in seven (4.6%) of 151 previously
      uncomplicated monochorionic diamniotic pregnancies, within 2 wk of a normal scan,
      at a median gestational age of 34(+1) wk (weeks(+days); range 28(+0) to 36(+3)).
      Two of the five cases that underwent autopsy had features suggestive of acute
      late onset twin-twin transfusion syndrome, but no antenatal indicators of
      transfusional imbalance or growth restriction, either empirically or in a 1:3
      gestation-matched case-control comparison. The prospective risk of unexpected
      antepartum stillbirth after 32 wk was 1/23 monochorionic diamniotic pregnancies
      (95% confidence interval 1/11 to 1/63). CONCLUSION: Despite intensive fetal
      surveillance, structurally normal monochorionic diamniotic twin pregnancies
      without TTTS or IUGR are complicated by a high rate of unexpected intrauterine
      death. This prospective risk of fetal death in otherwise uncomplicated
      monochorionic diamniotic pregnancies after 32 wk of gestation might be obviated
      by a policy of elective preterm delivery, which now warrants evaluation.

PMID- 15971950
TI  - How women were affected by the tsunami: a perspective from Oxfam.

PMID- 15971951
TI  - Addressing psychosocial needs in the aftermath of the tsunami.

PMID- 15971952
TI  - Uncomplicated monochorionic diamniotic twins and the timing of delivery.

PMID- 15971953
TI  - Weight loss and mortality: what does the evidence show?

PMID- 15971955
TI  - Revisiting the tsunami: health consequences of flooding.

PMID- 15971954
TI  - Development of a new vaccine for the prevention of Lassa fever.
AB  - BACKGROUND: Recent importation of Lassa fever into Germany, the Netherlands, the
      United Kingdom, and the United States by travelers on commercial airlines from
      Africa underscores the public health challenge of emerging viruses. Currently,
      there are no licensed vaccines for Lassa fever, and no experimental vaccine has
      completely protected nonhuman primates against a lethal challenge. METHODS AND
      FINDINGS: We developed a replication-competent vaccine against Lassa virus based
      on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa
      viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine
      elicited a protective immune response in nonhuman primates against a lethal Lassa
      virus challenge. Vaccine shedding was not detected in the monkeys, and none of
      the animals developed fever or other symptoms of illness associated with
      vaccination. The Lassa vaccine induced strong humoral and cellular immune
      responses in the four vaccinated and challenged monkeys. Despite a transient
      Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals
      showed no evidence of clinical disease. In contrast, the two control animals
      developed severe symptoms including rashes, facial edema, and elevated liver
      enzymes, and ultimately succumbed to the Lassa infection. CONCLUSION: Our data
      suggest that the Lassa vaccine candidate based on recombinant vesicular
      stomatitis virus is safe and highly efficacious in a relevant animal model that
      faithfully reproduces human disease.

PMID- 15971956
TI  - After the tsunami: legal implications of mass burials of unidentified victims in
      Sri Lanka.

PMID- 15971960
TI  - Call for biohistory guidelines.

PMID- 15971961
TI  - Some tolerance for fur--animal studies in PLoS Medicine.

PMID- 15971963
TI  - Comparison of changes in metal toxicity following exposure of water with high
      dissolved organic carbon content to solar, UV-B and UV-A radiation.
AB  - This study examines the effects of natural solar radiation on the metal-binding
      capacity of dissolved organic matter (DOM). Newington Bog water (35.5 mg L(-1)
      dissolved organic carbon [DOC]) was irradiated for 20 days under UV-B lamps in
      the laboratory and under natural solar radiation. In the presence of irradiated
      DOM, IC(50) (contaminant concentration required to reduce algal growth by 50%)
      was significantly decreased with UV-B treatment for four metals: Pb, 64%; Cu,
      63%; Ni, 35% and Cd, 40%. Solar radiation also significantly decreased IC(50) of
      Pb (58%) and Cu (49%), DOC concentration (11%), DOM fluorescence (DOMFL, 33%) and
      DOC-specific UV absorbance. Further experiments on Raisin River water (20.7 mg
      DOC L(-1)) exposed to 20 days of artificial UV-A and UV-B radiation produced
      significant decreases in IC(50) for Cu (48%) with UV-A and for Pb (43%) with UV
      B. DOC concentration was decreased 20% by UV-B and 24% by UV-A. DOMFL decreased
      51.5% in the first 5 days of UV-A exposure, an effect that was not observed with
      the UV-B treatment. The UV-A treatment decreased UV absorbance more at longer
      wavelengths and over a broader wavelength band than did the UV-B treatment.
      Change in toxicity with UV irradiation was inconsistent among the metals tested
      in this study, indicating that some organic metal-binding ligands were more
      quickly removed or altered than others. The DOM remaining after irradiation
      appears to be qualitatively different from the unirradiated DOM. The much greater
      irradiance of UV-A makes its contribution to the removal and/or alteration of DOM
      at least as important as the influence of higher energy UV-B.

PMID- 15971964
TI  - Rural and remote communities -- innovation in the midst of adversity.

PMID- 15971965
TI  - Development of a mentorship programme for rural general practitioners by visiting
      specialist physicians.

PMID- 15971970
TI  - Virtual environments for motor rehabilitation: review.
AB  - In this paper, the current "state of the art" for virtual reality (VR)
      applications in the field of motor rehabilitation is reviewed. The paper begins
      with a brief overview of available equipment options. Next, a discussion of the
      scientific rationale for use of VR in motor rehabilitation is provided. Finally,
      the major portion of the paper describes the various VR systems that have been
      developed for use with patients, and the results of clinical studies reported to
      date in the literature. Areas covered include stroke rehabilitation (upper and
      lower extremity training, spatial and perceptual-motor training), acquired brain
      injury, Parkinson's disease, orthopedic rehabilitation, balance training,
      wheelchair mobility and functional activities of daily living training, and the
      newly developing field of telerehabilitation. Four major findings emerge from
      these studies: (1) people with disabilities appear capable of motor learning
      within virtual environments; (2) movements learned by people with disabilities in
      VR transfer to real world equivalent motor tasks in most cases, and in some cases
      even generalize to other untrained tasks; (3) in the few studies (n = 5) that
      have compared motor learning in real versus virtual environments, some advantage
      for VR training has been found in all cases; and (4) no occurrences of
      cybersickness in impaired populations have been reported to date in experiments
      where VR has been used to train motor abilities.

PMID- 15971972
TI  - Virtual reality in psychotherapy: review.
AB  - Virtual reality (VR) has recently emerged as a potentially effective way to
      provide general and specialty health care services, and appears poised to enter
      mainstream psychotherapy delivery. Because VR could be part of the future of
      clinical psychology, it is critical to all psychotherapists that it be defined
      broadly. To ensure appropriate development of VR applications, clinicians must
      have a clear understanding of the opportunities and challenges it will provide in
      professional practice. This review outlines the current state of clinical
      research relevant to the development of virtual environments for use in
      psychotherapy. In particular, the paper focuses its analysis on both actual
      applications of VR in clinical psychology and how different clinical perspectives
      can use this approach to improve the process of therapeutic change.

PMID- 15971974
TI  - Virtual reality in brain damage rehabilitation: review.
AB  - Given the high incidence of brain injury in the population, brain damage
      rehabilitation is still a relatively undeveloped field. Virtual reality (VR) has
      the potential to assist current rehabilitation techniques in addressing the
      impairments, disabilities, and handicaps associated with brain damage. The main
      focus of much of the exploratory research performed to date has been to
      investigate the use of VR in the assessment of cognitive abilities, but there is
      now a trend for more studies to encompass rehabilitation training strategies.
      This review describes studies that have used VR in the assessment and
      rehabilitation of specific disabilities resulting from brain injury, including
      executive dysfunction, memory impairments, spatial ability impairments, attention
      deficits, and unilateral visual neglect. In addition, it describes studies that
      have used VR to try to offset some of the handicaps that people experience after
      brain injury. Finally, a table is included which, although not an exhaustive list
      of everything that has been published, includes many more studies that are
      relevant to the use of VR in the assessment and rehabilitation of brain damage.
      The review concludes that the use of VR in brain damage rehabilitation is
      expanding dramatically and will become an integral part of cognitive assessment
      and rehabilitation in the future.

PMID- 15971976
TI  - Virtual reality in the rehabilitation of people with intellectual disabilities:
      review.
AB  - Virtual reality (VR) possesses many qualities that give it rehabilitative
      potential for people with intellectual disabilities, both as an intervention and
      an assessment. It can provide a safe setting in which to practice skills that
      might carry too many risks in the real world. Unlike human tutors, computers are
      infinitely patient and consistent. Virtual worlds can be manipulated in ways the
      real world cannot be and can convey concepts without the use of language or other
      symbol systems. Published applications for this client group have all been as
      rehabilitative interventions. These are described in three groups: promoting
      skills for independent living, enhancing cognitive performance, and improving
      social skills. Five groups of studies are reviewed that utilize virtual
      technology to promote skills for independent living: grocery shopping, preparing
      food, orientation, road safety, and manufacturing skills. Fears that skills or
      habits learnt in a virtual setting would not transfer to the real world setting
      have not been supported by the available evidence, apart from those studies with
      people with autistic spectrum disorders. Future directions are in the development
      of more applications for independent living skills, exploring interventions for
      promoting motor and cognitive skills, and the developments of ecologically valid
      forms of assessment.

PMID- 15971980
TI  - Cells from cloned human embryos.

PMID- 15971981
TI  - Development of interspecies cloned embryos in yak and dog.
AB  - Interspecies nuclear transfer (NT) could be an alternative to replicate animals
      when supply of recipient oocytes is limited or in vitro embryo production systems
      are incomplete. In the present study, embryonic development was assessed
      following interspecies NT of donor cumulus cells derived from yak and dog into
      the recipient ooplasm of domestic cow. The percentages of fusion and subsequent
      embryo development to the eight-cell stage of interspecies NT embryos were
      comparable to those of intraspecies NT embryos (cow-cow NT embryos). The
      percentage of development to blastocysts was significantly lower (p < 0.05) in
      yak-cow NT embryos than that in cow-cow NT embryos (10.9% vs. 39.8%). In dog-cow
      NT embryos, only one embryo (0.4%) developed to the blastocyst stage. These
      results indicate that interspecies NT embryos possess equally developmental
      competence to the eight-cell stage as intraspecies NT embryos, but the
      development to blastocysts is very low when dog somatic cells are used as the
      donor nuclei.

PMID- 15971982
TI  - Challenges of primate embryonic stem cell research.
AB  - Embryonic stem (ES) cells hold great promise for treating degenerative diseases,
      including diabetes, Parkinson's, Alzheimer's, neural degeneration, and
      cardiomyopathies. This research is controversial to some because producing ES
      cells requires destroying embryos, which generally means human embryos. However,
      some of the surplus human embryos available from in vitro fertilization (IVF)
      clinics may have a high rate of genetic errors and therefore would be unsuitable
      for ES cell research. Although gross chromosome errors can readily be detected in
      ES cells, other anomalies such as mitochondrial DNA defects may have gone
      unrecognized. An insurmountable problem is that there are no human ES cells
      derived from in vivo-produced embryos to provide normal comparative data. In
      contrast, some monkey ES cell lines have been produced using in vivo-generated,
      normal embryos obtained from fertile animals; these can represent a "gold
      standard" for primate ES cells. In this review, we argue a need for strong
      research programs using rhesus monkey ES cells, conducted in parallel with
      studies on human ES and adult stem cells, to derive the maximum information about
      the biology of normal stem cells and to produce technical protocols for their
      directed differentiation into safe and functional replacement cells, tissues, and
      organs. In contrast, ES cell research using only human cell lines is likely to be
      incomplete, which could hinder research progress, and delay or diminish the
      effective application of ES cell technology to the treatment of human diseases.

PMID- 15971983
TI  - Long-term bovine hematopoietic engraftment with clone-derived stem cells.
AB  - Therapeutic cloning by somatic cell nuclear transfer offers potential for
      treatment of a wide range of degenerative disease. Nuclear transplantation with
      neo (r)-marked somatic nuclei from 10-13-year-old cows was used to generate
      cloned bovine fetuses. Clone fetal liver (FL) hematopoietic stem cells (HSC) were
      transplanted into two busulfan-treated and one untreated nuclear donor cows.
      Hematopoiesis was monitored over 13-16 months by in vitro progenitor and HSC
      assays. Chimerism was demonstrated by PCR in blood, marrow, lymph nodes, and
      endothelium, peaking at levels of 9-17% in blood granulocytes but at lower levels
      in lymphocyte subsets (0.1-0.01%). Circulating progenitors showed high levels of
      chimerism (up to 60% neo (r+)) with persisting fetal features. At sacrifice, the
      animal that had no pre-transplant myelosupression showed persisting donor cells
      in blood and lymph nodes, and in marrow 0.25% of progenitor cells and a
      detectable fraction of stem cells were neo (r+). The fetal HSC showed a 10-fold
      competition advantage over adult HSC. Cloning generated histocompatible HSC
      capable of long-term multilineage engraftment in a large animal model.

PMID- 15971984
TI  - Health and reproductive profiles of malaria antigen-producing transgenic goats
      derived by somatic cell nuclear transfer.
AB  - Nuclear transfer (NT) using transfected primary cells is an efficient approach
      for the generation of transgenic goats. However, reprogramming abnormalities
      associated with this process might result in compromised animals. We examined the
      health, reproductive performance, and milk production of four transgenic does
      derived from somatic cell NT. Goats were derived from two fetal cell lines, each
      transfected with a transgene expressing a different version of the MSP-1(42)
      malaria antigen, either glycosylated or non-glycosylated. Two female kids were
      produced per cell line. Health and growth of these NT animals were monitored and
      compared with four age-matched control does. There were no differences in birth
      and weaning weights between NT and control animals. The NT does were bred and
      produced a total of nine kids. The control does delivered five kids. The NT does
      expressing the glycosylated antigen lactated only briefly, probably as a result
      of over-expression of the MSP-1(42) protein. However, NT does expressing the non
      glycosylated antigen had normal milk yields and produced the recombinant protein.
      These data demonstrated that the production of healthy transgenic founder goats
      by somatic cell NT is readily achievable and that these animals can be used
      successfully for the production of a candidate Malaria vaccine.

PMID- 15971985
TI  - Progeny of somatic cell nuclear transfer (SCNT) pig clones are phenotypically
      similar to non-cloned pigs.
AB  - Systematic studies of cloned animals generated from adult somatic cell nuclei are
      critical in assessing the utility of somatic cell cloning in various
      applications, including the safety of food products from cloned animals and their
      offspring. Previously, we compared somatic cell derived cloned pigs with
      naturally bred control pigs on a series of physiological and genetic parameters.
      We have extended our studies to the F1 progeny of these clones to see whether
      these phenotypic differences are transmitted to the next generation. There were
      no differences in the average litter size between litters from cloned gilts and
      naturally bred controls (7.78 +/- 2.6 and 7.40 +/- 3.0, respectively; mean +/-
      SD) or in the degree of litter size variation (coefficients of variation of 33.4%
      and 40.5% for litters of clones and controls, respectively). Similarly there were
      no statistical differences between sex ratios of cloned litters (51-49%, M:F) and
      control litters (59-41%, M:F). Blood profiles between cloned pigs, control pigs,
      and their progeny were compared at two time points (i.e., 15 and 27 weeks) to
      quantify the effect of cloning on various blood parameters and their transmission
      to the next generation. Although the range of values for all traits overlapped
      between different classes, the variability between all the traits in F1 progeny
      of clones and the control pigs was similar at 15 and 27 weeks, with one
      exception. Combined, our data and previous results in mice strongly support the
      hypothesis that offspring of clones are similar to offspring of naturally bred
      animals, and as such there should not be any increased risks associated with
      consumption of products from these animals.

PMID- 15971986
TI  - Development of a zona-free method of nuclear transfer in the mouse.
AB  - In the present study, a zona-free nuclear transfer (NT) technique, which had been
      originally developed in cattle, was modified for the mouse. Steps involved in
      this approach include removing the zona pellucida and enucleating without a
      holding pipette; sticking donor cells to the cytoplast before electric pulses are
      applied to fuse them and culturing reconstructed embryos individually in single
      droplets, to prevent aggregation. Control zona-free and zona-intact embryos from
      mated donors showed no significant difference in development to blastocyst, but
      did show reduced development to term. Removal of the zona pellucida affected the
      response to activation by strontium in the absence of calcium as a significant
      proportion of zona-free control oocytes and embryos reconstructed by NT lysed
      during this treatment. A comparison between cumulus and ES cells as donor cells
      revealed significant differences in fusion efficiency (58.1 +/- 4.0%, n = 573 vs.
      42.9 +/- 2.2%, n = 2064, respectively, p < 0.001), cleavage (77.2 +/- 3.4%, n =
      334 vs. 40.8 +/- 2.7%, n = 903, respectively, p < 0.001) but not for development
      to morula/blastocyst (8.7 +/- 2.1%, n = 334 vs. 13.9 +/- 1.8%, n = 903,
      respectively, p < 0.1). The stage at which embryo development arrested was also
      affected by donor cell type. A majority of embryos reconstructed from cumulus
      cells arrested at two-cell stage, usually with two nuclei, whereas those
      reconstructed from ES cells arrested at one-cell stage, usually with two pseudo
      pronuclei. After transfer of ES cell-derived NT embryos, a viable cloned mouse
      was produced (3.0% of transferred embryos developed to term). These observations
      establish that a zona-free cloning approach is possible in the mouse, although
      further research is required to increase the efficiency.

PMID- 15971987
TI  - An interview with Sheila Collins, Ph.D. Interview by Vicki Glaser.

PMID- 15971988
TI  - Inflammatory pathway analysis using a high content screening platform.
AB  - High content cellular screening assays are useful tools to investigate the
      interplay between signaling pathways and offer valuable platforms to determine
      the mode of action, potency, and selectivity of potential drug candidates in a
      biological setting. We describe a cell-based multiplex fluorescent imaging assay
      that permits concurrent detection and quantification of the distribution of
      nuclear factor kappaB (NFkappaB) p65/RelA and phosphorylated forms of p38 and c
      Jun between the cytosol and nucleus. Cellular screening, data acquisition, and
      data interpretation were conducted on the ArrayScan HCS Reader (Cellomics Inc.,
      Pittsburgh, PA). A significant window between untreated and interleukin-1alpha
      (IL-1alpha) stimulated HeLa cells for all three targets was achieved with low
      variability. Staining specificity was confirmed with blocking peptides and
      pharmacological inhibition of p38, c-Jun-N-terminal kinase (JNK), and inhibitory
      kappaB kinase 2, and channel bleed-through was eliminated or counterbalanced by
      the use of fixed exposure times together with careful reporter channel selection.
      The JNK inhibitor SP600125 was used as a demonstration compound because in
      addition to inhibiting nuclear accumulation of phosphorylated c-Jun it reduced
      nuclear translocation of phosphorylated p38 and NFkappaB p65/RelA in a dose
      dependent manner, indicating a lack of SP600125 selectivity. This was supported
      by RNA interference where co-transfection of small interfering RNA targeting both
      JNK1 and JNK2, to limit signaling redundancy, significantly inhibited IL-1alpha
      stimulated translocation of phosphorylated c-Jun without altering phosphorylated
      p38 and NFkappaB p65/RelA redistribution. This image analysis application is a
      valuable and information-rich screening tool to investigate compound selectivity
      and/or cross-talk between key signaling pathways involved in the inflammatory
      response.

PMID- 15971989
TI  - Solid-phase immunoassays in mechanism-based drug discovery: their application in
      the development of inhibitors of the molecular chaperone heat-shock protein 90.
AB  - High-throughput screening of chemical libraries and the subsequent rapid progress
      of hit compounds through an iterative developmental test cascade are essential
      parts of modern molecular mechanism-based drug discovery. These processes depend
      on the use of efficient assay technologies and equipment. Enzyme-linked
      immunosorbent assays have historically been carried out in 96-well microtitre
      plates. Improvements in reagents and assay technologies mean that solid-phase
      immunoassays can be adapted for higher throughput to play an important role in
      modern drug discovery. The molecular chaperone heat-shock protein (Hsp) 90 is an
      important anticancer drug target because it maintains the conformation,
      stability, and function of many important oncogenic client proteins, including
      those involved with signal transduction, cell proliferation, survival,
      differentiation, motility angiogenesis, and metastasis. Using the standard
      inhibitors of the adenosine triphosphatase (ATPase) activity of Hsp90,
      geldanamycin (GA) and 17-allylamino-17- demethoxygeldanamycin (17AAG), novel
      solid-phase immunoassays have been validated using a time-resolved fluorescence
      (TRF) end point. Their utility for confirming the mechanism of action of Hsp90
      inhibition in secondary cell-based assays has been shown and applied to the novel
      Hsp90 inhibitor CCT018159. Adaptation of these assays for later studies using
      human tumour xenografts and samples obtained from a Phase 1 trial of 17AAG is
      also described. Finally, comparison is made between the use and applicability of
      this type of immunoassay and other techniques such as western blotting,
      immunohistochemistry, and flow cytometry analysis.

PMID- 15971990
TI  - A continuous time-resolved fluorescence assay for identification of BACE1
      inhibitors.
AB  - The aspartic protease beta-site amyloid precursor protein cleaving enzyme 1
      (BACE1) mediates the production of the neurotoxic amyloid beta peptide and is
      therefore considered an important drug target for treatment of Alzheimer's
      disease. We describe a new homogeneous time-resolved fluorescence quenching assay
      for the identification of BACE1 inhibitors that is characterized by minimal
      compound interference and allows both kinetic and end-point measurements. A
      fluorescent Eu-chelate as fluorescent donor, coupled to the N-terminus of a
      peptide containing the amyloid precursor protein Swedish mutation with a
      quenching molecule at the C-terminus as acceptor, is used as substrate. Upon
      peptide cleavage by BACE1, the energy transfer between donor and acceptor
      molecules is interrupted, leading to increased fluorescence emission of the
      donor. Compound interference, a common problem in fluorescence assays, is
      minimized with this technology because of the large Stoke's shift and the time
      resolved fluorescence emission of the Eu-chelate. The assay reproduced IC50
      values of known inhibitors and detected them also as hits in a screening
      campaign. A high signal-to-noise ratio of 289 and a Z' factor of 0.76 make this
      assay suitable for high-throughput screening.

PMID- 15971991
TI  - Microplates with integrated oxygen sensors for kinetic cell respiration
      measurement and cytotoxicity testing in primary and secondary cell lines.
AB  - This paper presents a cytotoxicity and cell respiration assay that is
      nondestructive and kinetic. It makes use of 96-well microplates integrated with
      oxygen sensors. The oxygen signal monitored on-line gives an indication of the
      cell viability. We show its application for suspension cell lines (Chinese
      hamster ovary and HL60 cells) as well as adherent (Caco2 cells) and primary (rat
      hepatocytes) cells using well-known cytotoxic compounds (sodium azide,
      diclofenac, clozapine, sodium dodecyl sulfate, 2-thiouracil, tamoxifen, and
      tranylcypromine). The 50% lethality concentration (LC50) obtained from the assay
      is compared with the standard 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl-2H
      tetrazolium bromide end-point assay. The cells can be grown directly in the
      plates, and the assay requires no further reagents or processing. The cells can
      be harvested for further analysis, if required. The on-line dynamic measurement
      allows the calculation of LC50 as a function of exposure time. LC50 was shown to
      decrease with time in HL60 cells. The dynamics of this process was considerably
      different for the three compounds sodium dodecyl sulfate, tamoxifen, and
      diclofenac, indicating a large potential of application of this method for cell
      death studies. The assay system can be applied to almost any cell-based systems
      with little adaptation. The assay is robust, flexible, and applicable for medium-
      to high-throughput systems requiring only minimal handling and no additional
      agent.

PMID- 15971992
TI  - Generation of cell lines for drug discovery through random activation of gene
      expression: application to the human histamine H3 receptor.
AB  - Target-based high-throughput screening (HTS) plays an integral role in drug
      discovery. The implementation of HTS assays generally requires high expression
      levels of the target protein, and this is typically accomplished using
      recombinant cDNA methodologies. However, the isolated gene sequences to many drug
      targets have intellectual property claims that restrict the ability to implement
      drug discovery programs. The present study describes the pharmacological
      characterization of the human histamine H3 receptor that was expressed using
      random activation of gene expression (RAGE), a technology that over-expresses
      proteins by up-regulating endogenous genes rather than introducing cDNA
      expression vectors into the cell. Saturation binding analysis using
      [125I]iodoproxyfan and RAGE-H3 membranes revealed a single class of binding sites
      with a K(D) value of 0.77 nM and a B(max) equal to 756 fmol/mg of protein.
      Competition binding studies showed that the rank order of potency for H3 agonists
      was N(alpha)-methylhistamine approximately (R)-alpha- methylhistamine > histamine
      and that the rank order of potency for H3 antagonists was clobenpropit >
      iodophenpropit > thioperamide. The same rank order of potency for H3 agonists and
      antagonists was observed in the functional assays as in the binding assays. The
      Fluorometic Imaging Plate Reader assays in RAGE-H3 cells gave high Z' values for
      agonist and antagonist screening, respectively. These results reveal that the
      human H3 receptor expressed with the RAGE technology is pharmacologically
      comparable to that expressed through recombinant methods. Moreover, the level of
      expression of the H3 receptor in the RAGE-H3 cells is suitable for HTS and
      secondary assays.

PMID- 15971993
TI  - Bispecific enzyme-linked signal-enhanced immunoassay with subattomole
      sensitivity.
AB  - A bispecific enzyme-linked signal-enhanced immunoassay (BiELSIA) was developed
      with markedly increased sensitivity. Antimyosin, the detection antibody, was
      linked to the signal probespecific antibody. Probes consisted of
      diethylenetriamine pentaacetic acids attached to polylysine modified with up to
      seven or eight horseradish peroxidase (HRP) units. Each bispecific antibody bound
      two polymer probes, providing twice the signal. Using BiELSIA in a competitive
      inhibition immunoassay format with an average of 1.5, 3, 4.5, 6, and 7.5 HRP
      units per polymer-probe, the sensitivity of standard enzyme-linked immunosorbent
      assay (10(13) mole) was increased to 10(15), 10(18), 10(19), 10(20), and 10(-21)
      mol (< or = 1,000 molecules), respectively. BiELSIA detected cardiac myosin heavy
      chain fragments in sera of patients obtained at the time of emergency department
      admission for acute myocardial infarction, but not in normal sera. This
      technology should be applicable for detection of cancer, human immunodeficiency
      virus, prion, and other antigens that are present in concentrations too low for
      detection by current immunoassays.

PMID- 15971994
TI  - New therapeutic approaches for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic polyarthritis leading to joint destruction
      and remarkable disability. Current therapies have various degrees of efficacy,
      but toxicity frequently limits their long-term use. Although the etiology of the
      disease remains unknown, our increasing knowledge of the mechanisms underlying
      pathogenic events in rheumatoid synovitis has enabled selective targeting of the
      pathogenic elements of disease. Several new drugs have recently been introduced
      for the treatment of RA. These include cyclooxygenase type 2 inhibitors, adhesion
      molecules, T cells, B cells, cytokine/receptor, chemokines, angiogenesis, oral
      tolerance antigens, costimulatory molecules, and new disease-modifying
      antirheumatic drugs. Continuing research into the pathogenesis of RA will
      undoubtedly identify even more effective therapeutic approaches for the
      management of this disease in the future. In conclusion, the proof of principle
      has been established that selective targeting of pathogenic elements of disease
      results in substantial improvement in signs and symptoms as well as disease
      progression. Improved efficacy is expected with more aggressive targeting of the
      pathogenic elements.

PMID- 15971998
TI  - AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab
      GTPase-activating protein domain.
AB  - Recently, we described a 160 kDa protein (designated AS160, for Akt substrate of
      160 kDa) with a predicted Rab GAP (GTPase-activating protein) domain that is
      phosphorylated on multiple sites by the protein kinase Akt. Phosphorylation of
      AS160 in adipocytes is required for insulin-stimulated translocation of the
      glucose transporter GLUT4 to the plasma membrane. The aim of the present study
      was to determine whether AS160 is in fact a GAP for Rabs, and, if so, what its
      specificity is. We first identified a group of 16 Rabs in a preparation of
      intracellular vesicles containing GLUT4 by MS. We then prepared the recombinant
      GAP domain of AS160 and examined its activity against many of these Rabs, as well
      as several others. The GAP domain was active against Rabs 2A, 8A, 10 and 14.
      There was no significant activity against 14 other Rabs. GAP activity was further
      validated by the finding that the recombinant GAP domain with the predicted
      catalytic arginine residue replaced by lysine was inactive. Finally, it was found
      by immunoblotting that Rabs 2A, 8A and 14 are present in GLUT4 vesicles. These
      results indicate that AS160 is a Rab GAP, and suggest novel Rabs that may
      participate in GLUT4 translocation.

PMID- 15971999
TI  - Effect of Na+ binding on the conformation, stability and molecular recognition
      properties of thrombin.
AB  - In the present work, the effect of Na+ binding on the conformational, stability
      and molecular recognition properties of thrombin was investigated. The binding of
      Na+ reduces the CD signal in the far-UV region, while increasing the intensity of
      the near-UV CD and fluorescence spectra. These spectroscopic changes have been
      assigned to perturbations in the environment of aromatic residues at the level of
      the S2 and S3 sites, as a result of global rigidification of the thrombin
      molecule. Indeed, the Na+-bound form is more stable to urea denaturation than the
      Na+-free form by approximately 2 kcal/mol (1 cal identical with 4.184 J).
      Notably, the effects of cation binding on thrombin conformation and stability are
      specific to Na+ and parallel the affinity order of univalent cations for the
      enzyme. The Na+-bound form is even more resistant to limited proteolysis by
      subtilisin, at the level of the 148-loop, which is suggestive of the more rigid
      conformation this segment assumes in the 'fast' form. Finally, we have used
      hirudin fragment 1-47 as a molecular probe of the conformation of thrombin
      recognition sites in the fast and 'slow' form. From the effects of amino acid
      substitutions on the affinity of fragment 1-47 for the enzyme allosteric forms,
      we concluded that the specificity sites of thrombin in the Na+-bound form are in
      a more open and permissible conformation, compared with the more closed structure
      they assume in the slow form. Taken together, our results indicate that the
      binding of Na+ to thrombin serves to stabilize the enzyme into a more open and
      rigid conformation.

PMID- 15972000
TI  - The selective recruitment of mRNA to the ER and an increase in initiation are
      important for glucose-stimulated proinsulin synthesis in pancreatic beta-cells.
AB  - Glucose acutely stimulates proinsulin synthesis in pancreatic beta-cells through
      a poorly understood post-transcriptional mechanism. In the present study, we
      demonstrate in pancreatic beta-cells that glucose stimulates the recruitment of
      ribosome-associated proinsulin mRNA, located in the cytoplasm, to the ER
      (endoplasmic reticulum), the site of proinsulin synthesis, and that this plays an
      important role in glucose-stimulated proinsulin synthesis. Interestingly, glucose
      has greater stimulatory effect on the recruitment of proinsulin mRNA to the ER
      compared with other mRNAs encoding secretory proteins. This, as far as we are
      aware, is the first example whereby mRNAs encoding secretory proteins are
      selectively recruited to the ER and provides a novel regulatory mechanism for
      secretory protein synthesis. Contrary to previous reports, and importantly in
      understanding the mechanism by which glucose stimulates proinsulin synthesis, we
      demonstrate that there is no large pool of 'free' proinsulin mRNA in the
      cytoplasm and that glucose does not increase the rate of de novo initiation on
      the proinsulin mRNA. However, we show that glucose does stimulate the rate of
      ribosome recruitment on to ribosome-associated proinsulin mRNA. In conclusion,
      our results provide evidence that the selective recruitment of proinsulin mRNA to
      the ER, together with increases in the rate of initiation are important mediators
      of glucose-stimulated proinsulin synthesis in pancreatic beta-cells.

PMID- 15972001
TI  - Who tangos with GOA?-Use of Gene Ontology Annotation (GOA) for biological
      interpretation of '-omics' data and for validation of automatic annotation tools.
AB  - The number of large-scale experimental datasets generated from high-throughput
      technologies has grown rapidly. Biological knowledge resources such as the Gene
      Ontology Annotation (GOA) database, which provides high-quality functional
      annotation to proteins within the UniProt Knowledgebase, can play an important
      role in the analysis of such data. The integration of GOA with analytical tools
      has proved to aid the clustering, annotation and biological interpretation of
      such large expression datasets. GOA is also useful in the development and
      validation of automated annotation tools, in particular text-mining systems. The
      increasing interest in GOA highlights the great potential of this freely
      available resource to assist both the biological research and bioinformatics
      communities.

PMID- 15972002
TI  - PRIME: automatically extracted PRotein Interactions and Molecular Information
      databasE.
AB  - With the exponentially increasing amount of information in the biomedical field,
      the significance of advanced information retrieval and information extraction, as
      well as the role of databases, has been increasing. PRIME is an integrated
      gene/protein informatics database based on natural language processing. It
      provides automatically extracted protein/family/gene/compound interaction
      information including both physical and genetic interactions, gene ontology based
      functions, and graphic pathway viewers. Gene/protein/family names and functional
      terms are recognized based on dictionaries developed in our laboratory. The
      interaction and functional information are extracted by syntactic dependencies
      and various phrase patterns. We have included about 920,000 (non-redundant)
      protein interactions and 360,000 annotated gene-function relationships for major
      eukaryotes. By combining the sequence and text information, the pathway
      comparison between two organisms and simple pathway deduction based on other
      organism interaction data, and pathway filtering using tissue expression data,
      are also available. This database is accessible at http://prime.ontology.ims.u
      tokyo.ac.jp:8081.

PMID- 15972003
TI  - Linking experimental results, biological networks and sequence analysis methods
      using Ontologies and Generalised Data Structures.
AB  - The structure of a closely integrated data warehouse is described that is
      designed to link different types and varying numbers of biological networks,
      sequence analysis methods and experimental results such as those coming from
      microarrays. The data schema is inspired by a combination of graph based methods
      and generalised data structures and makes use of ontologies and meta-data. The
      core idea is to consider and store biological networks as graphs, and to use
      generalised data structures (GDS) for the storage of further relevant
      information. This is possible because many biological networks can be stored as
      graphs: protein interactions, signal transduction networks, metabolic pathways,
      gene regulatory networks etc. Nodes in biological graphs represent entities such
      as promoters, proteins, genes and transcripts whereas the edges of such graphs
      specify how the nodes are related. The semantics of the nodes and edges are
      defined using ontologies of node and relation types. Besides generic attributes
      that most biological entities possess (name, attribute description), further
      information is stored using generalised data structures. By directly linking to
      underlying sequences (exons, introns, promoters, amino acid sequences) in a
      systematic way, close interoperability to sequence analysis methods can be
      achieved. This approach allows us to store, query and update a wide variety of
      biological information in a way that is semantically compact without requiring
      changes at the database schema level when new kinds of biological information is
      added. We describe how this datawarehouse is being implemented by extending the
      text-mining framework ONDEX to link, support and complement different
      bioinformatics applications and research activities such as microarray analysis,
      sequence analysis and modelling/simulation of biological systems. The system is
      developed under the GPL license and can be downloaded from
      http://sourceforge.net/projects/ondex/

PMID- 15972004
TI  - IMGT-Choreography for immunogenetics and immunoinformatics.
AB  - IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr),
      was created in 1989 at Montpellier, France. IMGT is a high quality integrated
      knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR),
      major histocompatibility complex (MHC) of human and other vertebrates, and
      related proteins of the immune system (RPI) which belong to the immunoglobulin
      superfamily (IgSF) and MHC superfamily (MhcSF). IMGT provides a common access to
      standardized data from genome, proteome, genetics and three-dimensional
      structures. The accuracy and the consistency of IMGT data are based on IMGT
      ONTOLOGY, a semantic specification of terms to be used in immunogenetics and
      immunoinformatics. IMGT-ONTOLOGY has been formalized using XML Schema (IMGT-ML)
      for interoperability with other information systems. We are developing Web
      services to automatically query IMGT databases and tools. This is the first step
      towards IMGT-Choreography which will trigger and coordinate dynamic interactions
      between IMGT Web services to process complex significant biological and clinical
      requests. IMGT-Choreography will further increase the IMGT leadership in
      immunogenetics and immunoinformatics for medical research (repertoire analysis of
      the IG antibody sites and of the TR recognition sites in autoimmune and
      infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research
      (IG and TR repertoires in farm and wild life species), genome diversity and
      genome evolution studies of the adaptive immune responses, biotechnology related
      to antibody engineering (single chain Fragment variable (scFv), phage displays,
      combinatorial libraries, chimeric, humanized and human antibodies), diagnostics
      (detection and follow up of residual diseases) and therapeutical approaches
      (grafts, immunotherapy, vaccinology). IMGT is freely available at
      http://imgt.cines.fr.

PMID- 15972005
TI  - Large-scale extraction of gene regulation for model organisms in an ontological
      context.
AB  - This paper presents an approach using syntactosemantic rules for the extraction
      of relational information from biomedical abstracts. The results show that by
      overcoming the hurdle of technical terminology, high precision results can be
      achieved. From abstracts related to baker's yeast, we manage to extract a
      regulatory network comprised of 441 pairwise relations from 58,664 abstracts with
      an accuracy of 83 - 90%. To achieve this, we made use of a resource of
      gene/protein names considerably larger than those used in most other biology
      related information extraction approaches. This list of names was included in the
      lexicon of our retrained partof- speech tagger for use on molecular biology
      abstracts. For the domain in question an accuracy of 93.6 - 97.7% was attained on
      Part-of-speech-tags. The method can be easily adapted to other organisms than
      yeast, allowing us to extract many more biologically relevant relations. The main
      reason for the comparable precision rates is the ontological model that was built
      beforehand and served as a guiding force for the manual coding of the
      syntactosemantic rules.

PMID- 15972006
TI  - Deriving an ontology for human gene expression sources from the CYTOMER database
      on human organs and cell types.
AB  - CYTOMER is a relational database of organs/tissues, cell types, physiological
      systems and developmental stages that currently focuses on the human system. From
      this database, we have derived an ontology for anatomical and morphological
      structures for the human organism which includes all embryonal stages and the
      cell types constituting these structures. The ontology has been transferred to
      the OWL format and is freely available for download at
      http://cytomer/bioinf.med.uni-goettingen.de.

PMID- 15972007
TI  - Utilizing weakly controlled vocabulary for sentence segmentation in biomedical
      literature.
AB  - Since biomedical texts contain a wide variety of domain specific terms, building
      a large dictionary to perform term matching is of great relevance. However, due
      to the existence of null boundary between adjacent terms, this matching is not a
      trivial problem. Moreover, it is known that generative words cannot be
      comprehensively included in a dictionary because their possible variations are
      infinite. In this study, we report our approach to dictionary building and term
      matching in biomedical texts. Large amount of terms with/without part-of-speech
      (POS) and/or category information were gathered, and a completion program
      generated approximately 1.36 million term variants to avoid stemming problems
      when matching terms. The dictionary was stored in a relational database
      management system (RDBMS) for quick lookup, and used by a matching program. Since
      the matching operation is not restricted to a substring surrounded by space
      characters, we can avoid the problem of null boundaries. This feature is also
      useful for generative words. Experimental results on GENIA corpus are promising:
      nearly half of the possible terms were correctly recognized as a meaningful
      segment, and most of the remaining half could be correctly recognized by some
      post-processing process, like chunking and further decomposition. It should be
      remarked that although we have not used term cost, connectivity cost, or
      syntactic information, reasonable segmentation and dictionary lookup were
      performed in most cases.

PMID- 15972008
TI  - Challenges for the identification of biological systems from in vivo time series
      data.
AB  - Modern methods of high-throughput molecular biology render it possible to
      generate time series of metabolite concentrations and the expression of genes and
      proteins in vivo. These time profiles contain valuable information about the
      structure and dynamics of the underlying biological system. This information is
      implicit and its extraction is a challenging but ultimately very rewarding task
      for the mathematical modeler. Using a well-suited modeling framework, such as
      Biochemical Systems Theory (BST), it is possible to formulate the extraction of
      information as an inverse problem that in principle may be solved with a genetic
      algorithm or nonlinear regression. However, two types of issues associated with
      this inverse problem make the extraction task difficult. One type pertains to the
      algorithmic difficulties encountered in nonlinear regressions with moderate and
      large systems. The other type is of an entirely different nature. It is a
      consequence of assumptions that are often taken for granted in the design and
      analysis of mathematical models of biological systems and that need to be
      revisited in the context of inverse analyses. The article describes the
      extraction process and some of its challenges and proposes partial solutions.

PMID- 15972009
TI  - Integrating data from biological experiments into metabolic networks with the DBE
      information system.
AB  - Modern 'omics'-technologies result in huge amounts of data about life processes.
      For analysis and data mining purposes this data has to be considered in the
      context of the underlying biological networks. This work presents an approach for
      integrating data from biological experiments into metabolic networks by mapping
      the data onto network elements and visualising the data enriched networks
      automatically. This methodology is implemented in DBE, an information system that
      supports the analysis and visualisation of experimental data in the context of
      metabolic networks. It consists of five parts: (1) the DBE-Database for
      consistent data storage, (2) the Excel-Importer application for the data import,
      (3) the DBE-Website as the interface for the system, (4) the DBE-Pictures
      application for the up- and download of binary (e. g. image) files, and (5) DBE
      Gravisto, a network analysis and graph visualisation system. The usability of
      this approach is demonstrated in two examples.

PMID- 15972010
TI  - Metabolites and pathway flexibility.
AB  - Flexibility of metabolites and enzymes is investigated (i) on the level of the
      individual molecule, (ii) on the pathway level and (iii) combined effects on the
      systems and network level. Tools and results from our current research are
      summarized including data from our metabolite enzyme database. Including our
      latest census we find frequently used metabolites stimulate evolutionary
      flexibility in specific enzyme superfamilies. Furthermore, simultaneous changes
      of reactions and metabolites are observed in these flexible enzyme superfamilies.
      Both effects provide a strong source for resistance in parasites and pathogens.
      Specific adaptations scenarios and some counter strategies are discussed.

PMID- 15972011
TI  - Dynamic cellular automata: an alternative approach to cellular simulation.
AB  - A wide variety of approaches, ranging from Petri nets to systems of partial
      differential equations, have been used to model very specific aspects of cellular
      or biochemical functions. Here we describe how an agent-based or dynamic cellular
      automata (DCA) approach can be used as a very simple, yet very general method to
      model many different kinds of cellular or biochemical processes. Specifically,
      using simple pairwise interaction rules coupled with random object moves to
      simulate Brownian motion, we show how the DCA approach can be used to easily and
      accurately model diffusion, viscous drag, enzyme rate processes, metabolism (the
      Kreb's cycle), and complex genetic circuits (the repressilator). We also
      demonstrate how DCA approaches are able to accurately capture the stochasticity
      of many biological processes. The success and simplicity of this technique
      suggests that many other physical properties and significantly more complicated
      aspects of cellular behavior could be modeled using DCA methods. An easy-to-use,
      graphically-based computer program, called SimCell, was developed to perform the
      DCA simulations described here. It is available at
      http://wishart.biology.ualberta.ca/SimCell/.

PMID- 15972012
TI  - A life-like virtual cell membrane using discrete automata.
AB  - A framework is presented that captures the discrete and probabilistic nature of
      molecular transport and reaction kinetics found in a living cell as well as
      formally representing the spatial distribution of these phenomena. This particle
      or agent-based approach is computationally robust and complements established
      methods. Namely it provides a higher level of spatial resolution than
      formulations based on ordinary differential equations (ODE) while offering
      significant advantages in computational efficiency over molecular dynamics (MD).
      Using this framework, a model cell membrane has been constructed with discrete
      particle agents that respond to local component interactions that resemble
      flocking or herding behavioural cues in animals. Results from simulation
      experiments are presented where this model cell exhibits many of the
      characteristic behaviours associated with its biological counterpart such as
      lateral diffusion, response to osmotic pressure gradients, membrane growth and
      cell division. Lateral diffusion rates and estimates for the membrane modulus of
      elasticity derived from these simple experiments fall well within a biologically
      relevant range of values. More importantly, these estimates were obtained by
      applying a simple qualitative tuning of the model membrane. Membrane growth was
      simulated by injecting precursor molecules into the proto-cell at different rates
      and produced a variety of morphologies ranging from a single large cell to a
      cluster of cells. The computational scalability of this methodology has been
      tested and results from benchmarking experiments indicate that real-time
      simulation of a complete bacterial cell will be possible within 10 years.

PMID- 15972013
TI  - The Integr8 project--a resource for genomic and proteomic data.
AB  - Integr8 (http://www.ebi.ac.uk/integr8/) is providing an integration layer for the
      exploitation of genomic and proteomic data by drawing on databases maintained at
      major bioinformatics centres in Europe. Main aims are to store the relationships
      of biological entities to each other and to entries in other databases, to
      provide a framework that allows for new kinds of data to be integrated, and to
      offer an entity-centric view of complete genomes and proteomes. Basic tools for
      data integration comprise the Proteome Analysis database, the International
      Protein Index (IPI), the Universal Protein sequence archive (UniParc) and the
      Genome Reviews. Entry points for the Integr8 portal depend on the users entity of
      interest: from browsing the taxonomy or with a predetermined species of interest,
      the species page can be used, and a simple search page leads to different
      applications when looking for certain protein sequences or genes. Customisable
      statistics data are available from the BioMart application, and pre-prepared data
      can be downloaded from the FTP site.

PMID- 15972014
TI  - Bioinformatics visualization and integration with open standards: the Bluejay
      genomic browser.
AB  - We have created a new Java-based integrated computational environment for the
      exploration of genomic data, called Bluejay. The system is capable of using
      almost any XML file related to genomic data. Non-XML data sources can be accessed
      via a proxy server. Bluejay has several features, which are new to
      Bioinformatics, including an unlimited semantic zoom capability, coupled with
      Scalable Vector Graphics (SVG) outputs; an implementation of the XLink standard,
      which features access to MAGPIE Genecards as well as any BioMOBY service
      accessible over the Internet; and the integration of gene chip analysis tools
      with the functional assignments. The system can be used as a signed web applet,
      Web Start, and a local stand-alone application, with or without connection to the
      Internet. It is available free of charge and as open source via
      http://bluejay.ucalgary.ca.

PMID- 15972015
TI  - Knowledge discovery and system biology in molecular medicine: an application on
      neurodegenerative diseases.
AB  - The possibility to study an organism in terms of system theory has been proposed
      in the past, but only the advancement of molecular biology techniques allow us to
      investigate the dynamical properties of a biological system in a more
      quantitative and rational way than before . These new techniques can gave only
      the basic level view of an organisms functionality. The comprehension of its
      dynamical behaviour depends on the possibility to perform a multiple level
      analysis. Functional genomics has stimulated the interest in the investigation
      the dynamical behaviour of an organism as a whole. These activities are commonly
      known as System Biology, and its interests ranges from molecules to organs. One
      of the more promising applications is the 'disease modeling'. The use of
      experimental models is a common procedure in pharmacological and clinical
      researches; today this approach is supported by 'in silico' predictive methods.
      This investigation can be improved by a combination of experimental and
      computational tools. The Machine Learning (ML) tools are able to process
      different heterogeneous data sources, taking into account this peculiarity, they
      could be fruitfully applied to support a multilevel data processing (molecular,
      cellular and morphological) that is the prerequisite for the formal model design;
      these techniques can allow us to extract the knowledge for mathematical model
      development. The aim of our work is the development and implementation of a
      system that combines ML and dynamical models simulations. The program is
      addressed to the virtual analysis of the pathways involved in neurodegenerative
      diseases. These pathologies are multifactorial diseases and the relevance of the
      different factors has not yet been well elucidated. This is a very complex task;
      in order to test the integrative approach our program has been limited to the
      analysis of the effects of a specific protein, the Cyclin dependent kinase 5
      (CDK5) which relies on the induction of neuronal apoptosis. The system has a
      modular structure centred on a textual knowledge discovery approach. The text
      mining is the only way to enhance the capability to extract ,from multiple data
      sources, the information required for the dynamical simulator. The user may
      access the publically available modules through the following site:
      http://biocomp.ge.ismac.cnr.it.

PMID- 15972016
TI  - An algorithm for linear metabolic pathway alignment.
AB  - Metabolic pathway alignment represents one of the most powerful tools for
      comparative analysis of metabolism. It involves recognition of metabolites common
      to a set of functionally-related metabolic pathways, interpretation of biological
      evolution processes and determination of alternative metabolic pathways.
      Moreover, it is of assistance in function prediction and metabolism modeling.
      Although research on genomic sequence alignment is extensive, the problem of
      aligning metabolic pathways has received less attention. We are motivated to
      develop an algorithm of metabolic pathway alignment to reveal the similarities
      between metabolic pathways. A new definition of the metabolic pathway is
      introduced. The algorithm has been implemented into the PathAligner system; its
      web-based interface is available at http://bibiserv.techfak.uni
      bielefeld.de/pathaligner/.

PMID- 15972017
TI  - STEPP--Search Tool for Exploration of Petri net Paths: a new tool for Petri net
      based path analysis in biochemical networks.
AB  - To understand biochemical processes caused by, e. g., mutations or deletions in
      the genome, the knowledge of possible alternative paths between two arbitrary
      chemical compounds is of increasing interest for biotechnology, pharmacology,
      medicine, and drug design. With the steadily increasing amount of data from high
      throughput experiments new biochemical networks can be constructed and existing
      ones can be extended, which results in many large metabolic, signal transduction,
      and gene regulatory networks. The search for alternative paths within these
      complex and large networks can provide a huge amount of solutions, which can not
      be handled manually. Moreover, not all of the alternative paths are generally of
      interest. Therefore, we have developed and implemented a method, which allows us
      to define constraints to reduce the set of all structurally possible paths to the
      truly interesting path set. The paper describes the search algorithm and the
      constraints definition language. We give examples for path searches using this
      dedicated special language for a Petri net model of the sucrose-to-starch
      breakdown in the potato tuber.

PMID- 15972018
TI  - Complementing computationally predicted regulatory sites in Tractor_DB using a
      pattern matching approach.
AB  - Prokaryotic genomes annotation has focused on genes location and function. The
      lack of regulatory information has limited the knowledge on cellular
      transcriptional regulatory networks. However, as more phylogenetically close
      genomes are sequenced and annotated, the implementation of phylogenetic
      footprinting strategies for the recognition of regulators and their regulons
      becomes more important. In this paper we describe a comparative genomics approach
      to the prediction of new gamma-proteobacterial regulon members. We take advantage
      of the phylogenetic proximity of Escherichia coli and other 16 organisms of this
      subdivision and the intensive search of the space sequence provided by a pattern
      matching strategy. Using this approach we complement predictions of regulatory
      sites made using statistical models currently stored in Tractor_DB, and increase
      the number of transcriptional regulators with predicted binding sites up to 86.
      All these computational predictions may be reached at Tractor_DB
      (www.bioinfo.cu/Tractor_DB, www.tractor.lncc.br,
      www.ccg.unam.mx/Computational_Genomics/tractorDB/). We also take a first step in
      this paper towards the assessment of the conservation of the architecture of the
      regulatory network in the gamma-proteobacteria through evaluating the
      conservation of the overall connectivity of the network.

PMID- 15972019
TI  - Comparison of 1- and 2-day protocols for myocardial SPECT: a Monte Carlo study.
AB  - BACKGROUND: Myocardial perfusion single-photon emission computed tomography
      (SPECT) is carried out by combining a rest and a stress study that are performed
      either on one day or two separate days. A problem when performing the two studies
      on 1 day is that the residual activity from the first study contributes to the
      activity measured in the second study. AIM: Our aim was to identify and evaluate
      trends in the quantification parameters of myocardial perfusion images as a
      function of separation time between rest and stress. METHODS: A digital phantom
      was used for the generation of heart images and a Monte Carlo-based scintillation
      camera program was used to simulate SPECT projection images. In our simulations,
      the rest images were normal and the stress images included lesions of different
      types and localization. Two programs for quantification of myocardial perfusion
      images were used to assess the different images in an automated and objective
      way. RESULTS: The summed difference scores observed with the 2-day protocol were
      3 +/- 1 (mean +/- SD) higher for AutoQUANT and 2 +/- 1 higher for 4D-MSPECT
      compared with those observed with the 1-day protocol. The extent values were 2%
      points higher for the 2-day protocol compared with the 1-day protocol for both
      programs. CONCLUSIONS: There are differences in the quantitative assessment of
      perfusion defects depending on the type of protocol used. The contribution of
      residual activity is larger when a 1-day protocol is used compared with the 2-day
      protocol. The differences, although small, are of a magnitude that results in a
      clear shift in quantification parameters.

PMID- 15972020
TI  - Radiation doses to staff involved in sentinel node operations for breast cancer.
AB  - BACKGROUND: The use of radioactive compounds for sentinel node biopsy is now a
      generally accepted part of the surgical treatment of breast cancer and melanoma,
      with the risk of radiation exposure to the operating team. The aim of this
      investigation was to study the levels of this exposure in relation to the
      permissible radiation dose limits. METHODS: The radiation exposure to the hands
      and bodies of the operating surgeons (the 'risk persons') was measured by
      thermoluminescent dosimeters in 79 operations and to the pathologists handling
      the specimens in 17 cases. Radioactivity and dose rate measurement from tumours
      and breast specimens were also performed. RESULTS: During an operation the mean
      skin dose (+/-SD) to the thermoluminescent dosimeters placed at the hand and the
      abdominal wall were 0.04 +/- 0.04 mSv (79 operations) and 0.01 +/- 0.02 mSv (67
      operations) respectively. For the pathologist, the mean hand dose per operation
      was below the detection limit (17 operations). Correlation between the measured
      dose rate and the radioactive content of the tumours was 0.998. CONCLUSIONS: The
      radiation exposure to the staff involved in sentinel node (SN) biopsy for breast
      cancer using radioactive labelled tracers will be considerably below the
      permissible limits, even with high numbers of SN biopsy procedures. Pregnant
      staff members should participate in <100 SN operations.

PMID- 15972021
TI  - Vastus lateralis oxygenation and blood volume measured by near-infrared
      spectroscopy during whole body vibration.
AB  - The purpose of this study was to investigate the effects of whole body vibration
      (WBV) on oxygenation of vastus lateralis muscle during squatting exercise.
      Eighteen male subjects [mean age, 27.3 +/- 6.0 (SD) years; mean height, 171.8 +/-
      4.9 cm; mean weight, 64.4 +/- 6.1 kg] performed squatting exercise on a vibration
      platform for 3 min with and without vibration, and changes in oxygenation of the
      vastus lateralis muscle were determined by near-infrared spectroscopy. The muscle
      oxygenation levels and total haemoglobin and myoglobin levels (total Hb/Mb)
      decreased during squatting exercise with and without vibration. After exercise,
      the muscle oxygenation level and total Hb/Mb rapidly increased from the minimum
      value during exercise and remained constant for latter 10 min. The muscle
      oxygenation levels with vibration from 90 to 180 s after the start of squatting
      exercise were significantly lower than those without vibration. Total Hb/Mb with
      vibration from 90 s after the squatting exercise to 540 s were significantly
      higher than those without vibration. This study demonstrated that WBV exercise
      affects the oxygenation level of vastus lateralis muscle and reduces muscle
      oxygenation level compared to that with no WBV. Therefore, WBV exercise may be an
      efficient training stimulus for muscle deoxygenation.

PMID- 15972022
TI  - Infarct transmurality and adjacent segmental function as determinants of wall
      thickening in revascularized chronic ischemic heart disease.
AB  - BACKGROUND: There are many factors which influence regional left ventricular wall
      thickening (WT) in ischemic heart disease (IHD). We used magnetic resonance
      imaging (MRI) to explore, in patients with chronic ischemic heart disease (CIHD),
      how regional WT is affected by both infarct transmurality (IT) and the function
      of adjacent segments. We also compared these findings with a group of healthy
      volunteers (controls). METHODS: Twenty patients (20 men, mean age 63, range 45-80
      years) were imaged with cine MRI for function and delayed enhancement MRI for
      infarction 6 months after revascularization. Twenty age and sex matched controls
      underwent cine MRI. Short-axis images were analysed using a 12-segment per slice
      model in four midventricular slices per subject. RESULTS: WT and IT were
      inversely related (r(2) = 0.11, P<0.001). WT of non-infarcted segments in
      patients was lower than corresponding segments in controls (5.1 versus 4.6 mm,
      P<0.001). WT in patients decreased with an increasing number of dysfunctional
      adjacent segments (P<0.001) and increasing IT (P<0.001). WT was more strongly
      influenced by the number of dysfunctional adjacent segments (t = -22.93, P<0.001)
      than by IT (t = -4.50, P<0.001). CONCLUSIONS: The number of dysfunctional
      adjacent segments is a greater determinant than infarct transmurality on regional
      wall thickening.

PMID- 15972023
TI  - Quantitative polar representation of left ventricular myocardial perfusion,
      function and viability using SPECT and cardiac magnetic resonance: initial
      results.
AB  - BACKGROUND: The clinical management of patients with coronary artery disease
      (CAD) often involves a complex assessment of the extent and severity of changes
      in left ventricular (LV) myocardial perfusion, function and viability. We aimed
      to explore the feasibility of integrative quantitative representation of LV
      perfusion, function and viability in adjacent polar plots. In order to assess the
      clinical usefulness of the quantitative methods, we also explored the
      relationship and determined the agreement between visual scoring and quantitative
      measurement of regional perfusion and function. METHODS: Ten patients with CAD
      underwent rest and stress (99m)Tc-tetrofosmin single photon emission computed
      tomography (SPECT) and cardiac magnetic resonance (CMR) imaging. Software was
      developed in-house for generating polar plots from semi-automatic quantification
      of rest and stress perfusion from SPECT, function from cine CMR and viability
      from delayed contrast enhancement (DE) CMR. The agreement between visual
      assessment and quantification of both perfusion and function was tested by
      Kendall's coefficient of concordance (W). RESULTS: Polar plots were created using
      quantitative data from the semi-automatic analysis of perfusion, function and
      viability. Kendall's W for agreement between quantitative measurement and visual
      scoring was 1.0 (P<0.001) for perfusion and 0.85 (P<0.001) for function.
      CONCLUSIONS: Side-by-side quantitative polar representation of LV perfusion,
      function and viability is feasible and may aid in the complex assessment of these
      parameters. The agreement between quantitative measurement and visual scoring was
      very good for both perfusion and function.

PMID- 15972024
TI  - Comparison between fundamental and second-harmonic imaging echocardiography for
      calculation of left ventricular mass in children.
AB  - In adults, calculation of left ventricular mass (LVM) has been shown to give
      higher values when based on M-mode measurements obtained by the second-harmonic
      imaging (SHI) technique than with the older fundamental imaging (FI) technique.
      No information is available in paediatric subjects. This study, therefore,
      compares LVM calculated from measurements obtained with SHI and FI in 14
      children, aged 6.9-13.0 years. M-mode tracings were obtained in accordance with
      American Society of Echocardiography (ASE) recommendations. Three experienced
      sonographers performed measurements on each subject with both SHI and FI. The
      mean value was used in all calculations. LVM was calculated according to ASE
      convention and indexed by body surface area. LVM mean values were 58.9 +/- 9.7 g
      m(-2) for SHI and 57.8 +/- 8.2 g m(-2) for FI (P = 0.45). This preliminary study
      in a small group of paediatric subjects demonstrates no systematic differences
      between FI and SHI modalities in the calculation of LVM. The likely explanation
      is that the left ventricular endocardial border is usually well visualized with
      SHI as well as with FI in children.

PMID- 15972025
TI  - Center of volume and total heart volume variation in healthy subjects and
      patients before and after coronary bypass surgery.
AB  - BACKGROUND: Total heart volume variation (THVV) and center of volume variation
      (COVV) likely affects the efficiency of cardiac pumping, but no study has
      determined COVV of the heart throughout the cardiac cycle or the effect of
      surgery on THVV in adults. Therefore, the purposes of this study were to
      determine COVV in healthy adults and patients with cardiac failure due to
      ischemic heart disease (IHD), identify any difference in THVV between these two
      groups, and determine how these parameters are affected by coronary bypass
      surgery. METHODS: Six healthy volunteers and eight patients before and after
      surgery were investigated with cardiovascular magnetic resonance imaging. The
      atrioventricular plane movement (AVPM), THVV and time resolved three-dimensional
      coordinates of the center of the cardiac volume (COVV) were measured. RESULTS:
      COVV followed a loop in 3D space that between the end-points was approximately 2
      mm with no difference between healthy subjects and patients before surgery (P =
      0.093), although AVPM was significantly lower in patients (P = 0.002). However,
      after surgery the COVV during the cardiac cycle doubled (P = 0.012) and the
      increase in THVV was significant (P = 0.050), although of very small magnitude,
      and the AVPM remained unchanged (P = 0.401). CONCLUSION: COVV and THVV were
      similar in patients and healthy subjects even though AVPM was lower in the
      patient population. After surgery, however, COVV doubled despite a very small
      change in THVV and no change in AVPM. Taken together, the results of this study
      may provide new insights into the energy expenditure and efficiency of cardiac
      pumping.

PMID- 15972026
TI  - A new automated method for analysis of gated-SPECT images based on a three
      dimensional heart shaped model.
AB  - A new automated method for quantification of left ventricular function from gated
      single photon emission computed tomography (SPECT) images has been developed. The
      method for quantification of cardiac function (CAFU) is based on a heart shaped
      model and the active shape algorithm. The model contains statistical information
      of the variability of left ventricular shape. CAFU was adjusted based on the
      results from the analysis of five simulated gated-SPECT studies with well defined
      volumes of the left ventricle. The digital phantom NURBS-based Cardiac-Torso
      (NCAT) and the Monte-Carlo method SIMIND were used to simulate the studies.
      Finally CAFU was validated on ten rest studies from patients referred for routine
      stress/rest myocardial perfusion scintigraphy and compared with Cedar-Sinai
      quantitative gated-SPECT (QGS), a commercially available program for
      quantification of gated-SPECT images. The maximal differences between the CAFU
      estimations and the true left ventricular volumes of the digital phantoms were 11
      ml for the end-diastolic volume (EDV), 3 ml for the end-systolic volume (ESV) and
      3% for the ejection fraction (EF). The largest differences were seen in the
      smallest heart. In the patient group the EDV calculated using QGS and CAFU showed
      good agreement for large hearts and higher CAFU values compared with QGS for the
      smaller hearts. In the larger hearts, ESV was much larger for QGS than for CAFU
      both in the phantom and patient studies. In the smallest hearts there was good
      agreement between QGS and CAFU. The findings of this study indicate that our new
      automated method for quantification of gated-SPECT images can accurately measure
      left ventricular volumes and EF.

PMID- 15972027
TI  - Challenge-induced plasma exudation and mucinous secretion in human airways.
AB  - Secretion of mucins and exudation of plasma are distinct processes of importance
      to innate immunity and inflammatory disease. Yet, little is known about their
      relation in human airways. The objective of the present study was to use the
      human nasal airway to determine mucinous secretion and plasma exudation in
      response to common challenge agents and mediators. Ten healthy volunteers were
      subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was
      exposed to increasing doses of histamine (40 and 400 microg ml(-1)), methacholine
      (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a
      global marker of mucinous secretion and alpha(2)-macroglobulin as an index of
      exudation of bulk plasma. All challenge agents increased the mucosal output of
      fucose to about the same level (P<0.01-0.05). Once significant secretion had been
      induced the subsequently increased dose of the challenge agent, in the case of
      histamine and methacholine, failed to further increase the response. Only
      histamine increased the mucosal output of alpha(2)-macroglobulin (P<0.01). We
      conclude that prompt but potentially rapidly depleted mucinous secretion is
      common to different kinds of airway challenges, whereas inflammatory histamine
      type mediators are required to produce plasma exudation. Along with the
      acknowledged secretion of mucins, a practically non-depletable, pluripotent
      mucosal output of plasma emerges as an important component of the innate immunity
      of human airways.

PMID- 15972028
TI  - ST-segment deviations during pacing-induced increased heart rate in patients
      without coronary artery disease.
AB  - INTRODUCTION: In order to interpret ST-segment changes as an indicator of
      ischemia in patients with higher heart rates (HRs), the relation between ST
      segment levels and HR needs to be well defined in subjects without coronary
      artery disease. METHODS: Eighteen patients with normal ECGs in the
      catheterization laboratory, after radiofrequency ablation of AV nodal re-entry
      tachycardia or an accessory pathway were included. Computerized online
      vectorcardiography (VCG) was performed during step-wise atrial pacing-induced
      increases in HR up to 150 beats min(-1) (bpm). The ST-vector magnitude (ST-VM)
      and the relative ST change vector magnitude (STC-VM) were analysed at the J
      point, J + 20 and J + 60 ms. RESULTS: There was no divergence in the course of ST
      VM or STC-VM based on J point + 0, 20, or 60 ms during increasing HR. The STC-VM
      mean values increased progressively during increases in HR above 100 bpm, with an
      average increase in STC-VM of 15-20 microV per 10 bpm increases in HR. The ST-VM
      response during HR increases showed a heterogeneous and unpredictable pattern.
      CONCLUSION: The STC-VM increases linearly with rising HRs above 100 bpm. The STC
      VM can exceed widely recognized ischemic thresholds during higher HRs in the
      absence of ischemia. The choice of J point time to ST-VM measurements as tested
      here is not important for the STC-VM relation to HR at these HR levels. Further
      clinical testing is needed to improve the diagnostic specificity of STC-VM
      measurements during increased HRs.

PMID- 15972030
TI  - Towards an Australian national cardiac surgery database.

PMID- 15972031
TI  - Surgical research society of Australasia.

PMID- 15972032
TI  - Validation of Euroscore model in an Australian patient population.
AB  - BACKGROUND: The purpose of the present paper was to assess the performance of the
      European system for cardiac operative risk evaluation (EuroSCORE) model in an
      Australian adult cardiac surgical population. METHODS: The additive and logistic
      EuroSCORE models were retrospectively applied to predict operative mortality in
      2106 consecutive patients undergoing cardiac surgery at St Vincent's Hospital,
      Melbourne between June 2001 and August 2003, and at Geelong Hospital between June
      2001 and April 2004. The entire cohort and a subset of patients undergoing
      isolated coronary artery bypass graft (CABG) surgery were analysed. Model
      discrimination and calibration was tested by determining the area under the
      receiver operating characteristic (ROC) curve and Hosmer-Lemeshow chi2,
      respectively. RESULTS: There were significant differences in the prevalence of
      risk factors between the Australian and European cardiac surgical populations.
      There were 81 deaths (observed mortality 3.85%) in the entire cohort and 39
      deaths in the isolated CABG group (observed mortality 2.60%). The EuroSCORE
      models overestimated mortality (entire cohort: additive predicted 5.75%, logistic
      predicted 9.93%; isolated CABG: additive predicted 4.87%, logistic predicted
      7.71%). Discriminative power was very good for the entire cohort (area under ROC
      curve, 0.81 (additive) and 0.82 (logistic)). Calibration of both models was poor.
      CONCLUSION: The additive and logistic EuroSCORE model of risk prediction was not
      validated in the present population of cardiac surgical patients. The models may
      not accurately predict outcomes of patients undergoing cardiac surgery in
      Australia.

PMID- 15972033
TI  - Outcome of oesophagectomy for adenocarcinoma of the oesophagus and
      oesophagogastric junction.
AB  - BACKGROUND: Oesophageal adenocarcinoma is becoming an increasingly important
      problem in the Western world. Its incidence is increasing and its prognosis is
      poor. Because most reports of outcomes following oesophagectomy include patients
      with squamous cell carcinoma, the outcome following oesophagectomy for
      adenocarcinoma was evaluated at Flinders Medical Centre, Royal Adelaide Hospital
      and associated private hospitals. METHODS: The study group consisted of 121
      patients with oesophageal adenocarcinoma or adenocarcinoma of the
      oesophagogastric junction who underwent an attempted oesophagectomy between 1985
      and 2003. Thirty-two of these patients underwent surgery before 1999 at the Royal
      Adelaide Hospital. These patients were reviewed retrospectively. In 1999 the
      recording of details of all patients undergoing oesophagectomy was commenced on a
      prospectively maintained database. From 1999 to 2003, 89 patients underwent
      oesophagectomy at either the Royal Adelaide Hospital, Flinders Medical Centre or
      associated private hospitals. Overall, there were 101 male and 20 female
      patients, with a median age at surgery of 63 years (range 36-80). Survival data
      were available for all patients. The present study analysed factors affecting
      survival in these patients. RESULTS: Tumours were located entirely within the
      oesophagus in 83 patients, and involved the gastro-oesophageal junction in 38.
      Eighty-nine underwent an Ivor Lewis oesophagectomy; 20, a cervico-thoraco
      abdominal oesophagectomy; nine, a cervico-abdominal oesophagectomy (with either
      transhiatal or blunt oesophageal dissection); and four procedures were abandoned.
      Sixty-four per cent of patients had evidence of Barrett's oesophagus in the
      resection specimen. The overall resection rate was 97%. Significant postoperative
      morbidity occurred in 36%, and the in-hospital mortality rate was 5% (30-day
      mortality 3%). The overall 1-year survival rate was 80%, and the 5-year survival
      rate (including surgical deaths) was 20%. Poorer survival was associated with
      advanced T stage, and lymph node metastasis. The outcome following resection of
      tumours confined to the oesophagus was similar to that for tumours involving the
      gastro-oesophageal junction. Since 2000, the number of oesophagectomies performed
      in men for adenocarcinoma has doubled, whereas the number performed in women and
      for squamous cell carcinoma has remained constant. CONCLUSIONS: Oesophagectomy
      can be performed for patients with adenocarcinoma with an acceptable
      perioperative mortality rate. However, the longer term outlook following
      oesophagectomy for most patients with adenocarcinoma remains poor. Nevertheless,
      early stage tumours are associated with much better survival. For this reason,
      efforts to diagnose this disease at an early stage are likely to offer the best
      chance for improving outcomes.

PMID- 15972035
TI  - Reoperative pancreaticoduodenectomy for periampullary carcinoma.
AB  - BACKGROUND: Potentially resectable periampullary tumours may not be treated
      appropriately due to lack of local expertise in both assessment of resectability
      and resection in referring centres. Tata Memorial Hospital is a major referral
      centre for oncology and these patients are finally referred to this institution.
      In carefully selected patients, resection can be accomplished. The purpose of the
      present paper was to determine the perioperative morbidity and mortality for
      patients undergoing reoperative pancreaticoduodenectomy at a major comprehensive
      cancer centre. METHODS: Between January 1991 and December 2001 15 patients, who
      had undergone previous non-resectional surgery for operable periampullary
      carcinoma, underwent re-exploration. The perioperative morbidity and mortality
      were analysed and compared with that of the group of patients undergoing primary
      pancreaticoduodenectomy (143 patients) in the same period. RESULTS: All the 15
      patients undergoing re-exploration had a successful resection by
      pancreaticoduodenectomy. In the reoperative group eight patients (53%) underwent
      classic pancreaticoduodenectomy and seven patients (46%) had a pylorus-preserving
      pancreaticoduodenectomy, as compared to 102 (71%) and 41 (29%) patients in the
      primary surgery group, respectively. Although the mean operative time and the
      estimated blood loss were higher in the reoperative group, the morbidity and
      mortality rates were similar in the two groups. The overall 30-day mortality rate
      was 6.6% and 6.9% in the reoperative and the primary surgery group, respectively.
      Major morbidity occurred in two of the 15 patients (13.3%), and one patient
      (6.6%) died following surgery in the reoperative group. CONCLUSION: Reoperative
      pancreaticoduodenectomy can be performed safely in carefully selected patients
      with resectable, localized periampullary tumours with similar morbidity and
      mortality to patients undergoing primary surgery.

PMID- 15972037
TI  - Detecting curable disease following hepatectomy for colorectal metastases.
AB  - INTRODUCTION: Although resection may be curative for patients with hepatic
      colorectal metastases, recurrence occurs in the majority. Recurrence is
      occasionally amenable to repeated resection. The aim of the present study was to
      evaluate which modalities, at what intervals, detected potentially curable
      resection. METHODS: The records of patients undergoing hepatectomy for colorectal
      metastases over 10 years in one centre were retrospectively reviewed to determine
      when and how recurrence was diagnosed. Specific attention was paid to the
      detection of potentially curable disease. RESULTS: Of 41 recurrences, 22 occurred
      in the first year postoperatively, 21 of which were suitable for palliative
      treatment only. Ten of 19 recurrences occurring after 1 year underwent
      potentially curative intervention, 10 were diagnosed by computed tomography (CT).
      Carcinoembryonic antigen did not diagnose any curable recurrence. CONCLUSIONS: A
      follow-up protocol is proposed, based on annual CT.

PMID- 15972039
TI  - Total thyroidectomy replaces subtotal thyroidectomy as the preferred surgical
      treatment for Graves' disease.
AB  - BACKGROUND: Total thyroidectomy is increasingly being adopted for patients
      requiring surgical treatment for Graves' disease based on a comparable surgical
      risk and the lack of recurrence, as well as the questionable ability of subtotal
      thyroidectomy to maintain euthyroidism. The purpose of the present paper was to
      evaluate its safety and efficiency. METHODS: Total thyroidectomy was adopted as
      part of the routine surgical treatment for Graves' disease from 2000. Patients
      who underwent subtotal thyroidectomy (STT) from 1995 to 1999 (n = 119) were
      compared with those who underwent total thyroidectomy (TT) from 2000 to 2003 (n =
      98) with respect to immediate postoperative morbidity and long-term outcome.
      RESULTS: Fourteen (11.8%) and 22 patients (22.4%) required calcium supplement on
      discharge in the STT and TT groups, respectively (P < 0.05). One (0.8%) and three
      patients (3.1%) developed permanent hypocalcaemia, respectively. Transient
      recurrent laryngeal nerve palsy occurred in 9.2% (n = 11) and 5.1% (n = 5) of
      patients or 5.0% and 2.6% of nerves at risk after STT and TT, respectively. None
      of the patients had permanent nerve palsy. The estimated blood loss was less and
      hospital stay shorter after TT. During a mean follow up of 64 months, 86 patients
      (72.3%) in the STT group required thyroxine replacement and seven patients (5.9%)
      developed relapse. CONCLUSION: Subtotal thyroidectomy was associated with relapse
      as well as hypothyroidism in a significant proportion of patients during long
      term follow up. Total thyroidectomy can be performed as safely as STT and should
      be recommended as the procedure of choice for patients requiring surgical
      treatment for Graves' disease.

PMID- 15972040
TI  - Recovery of parathyroid function after total thyroidectomy: long-term follow-up
      study.
AB  - BACKGROUND: To prevent postoperative hypoparathyroidism following total
      thyroidectomy, the parathyroid glands are preserved in situ and/or resected or
      devascularized parathyroid glands are autotransplanted. A retrospective
      investigation was conducted utilizing biochemical and specific endocrine
      assessments to evaluate the difference in recovery of parathyroid function in the
      long term. METHODS: A total of 103 patients underwent total thyroidectomy at
      Second Department of Surgery, School of Medicine, Kagawa University between 1990
      and 1998. These patients were divided into a preservation group (n = 17), with
      only preserved glands in situ; a combination group (n = 72), consisting of
      patients with one or more parathyroid glands preserved in situ and one or more
      autotransplanted parathyroid glands; and an autotransplantation group (n = 14),
      with only transplanted glands. RESULTS: The overall incidence of permanent
      hypoparathyroidism in the preservation group, the combination group, and the
      autotransplantation group was 0%, 1.4%, and 21.4%, respectively. The mean levels
      of intact parathyroid hormone in the preservation group, the combination group,
      and the autotransplantation group recovered to 102%, 107%, and 50% of the
      preoperative levels at 5-year follow up. CONCLUSION: The results of the present
      study suggest that parathyroid glands should be preserved in situ whenever
      possible, to promote better recovery of postoperative function, and that only
      autotransplantation produces inadequate recovery of long-term function.

PMID- 15972041
TI  - Recommendations for the management of cystic thyroid nodules.
AB  - BACKGROUND: The management of cystic thyroid nodules has not been standardized
      with respect to an initial fine-needle aspiration cytology (FNAC) cystic change
      result, which is defined as fluid aspiration and a smear with numerous
      macrophages but scant or no follicular cells. In the present study the physical
      characteristics of cystic thyroid nodules predictive of the pathology were
      investigated, and recommendations made on their management. METHODS: The
      aspiration results of 1436 thyroid nodules managed between 1998 and 2000 were
      investigated. A total of 157 patients who had a subsequent operation or follow-up
      data with reaspiration were the subjects of the present study. Age, sex, nodule
      characteristics and others were examined as possible predictors of cancer risk.
      RESULTS: The malignancy rate was 8.9%. Ten cases (71%) of malignancy were not
      cytologically diagnosed. Male sex and a nodule size of > or = 4 cm were found to
      be statistically significant predictors of malignancy. The malignancy rate was
      highest (100%) when a cystic lesion had malignant cytology on reaspiration and
      local invasion on radiology. CONCLUSIONS: When a cystic change is observed by
      initial FNAC of thyroid nodules, nodules of > or = 4 cm must be reaspirated and a
      firm cytologic diagnosis made to rule out malignancy. Nodules should be
      considered for surgery having taken into account other characteristics, in
      particular male sex and radiologic findings of local invasion.

PMID- 15972042
TI  - Radial nerve morbidity in radial artery free flaps: harvest of cephalic vein
      versus venae comitantes.
AB  - BACKGROUND: The purpose of the present paper was to determine the radial nerve
      morbidity associated with harvest of different venous conduits in the radial
      artery free flap. METHODS: Retrospective study comparing subjective and objective
      symptoms of radial nerve morbidity in 51 consecutive free flaps over a 3-year
      period. RESULTS: Damage to the radial nerve occurred in 9% (1/11) of patients in
      the cephalic vein group versus 18% (4/28) in the venae comitante group.
      CONCLUSIONS: Raising the cephalic vein for venous drainage in the radial artery
      free flap doubles the incidence of radial nerve morbidity.

PMID- 15972043
TI  - Regional anaesthesia and propofol sedation for carotid endarterectomy.
AB  - BACKGROUND: Many surgeons now perform carotid endarterectomy under regional
      anaesthesia. The aim of the present study was to review a sedation technique
      using a computer-controlled infusion of propofol. METHODS: A consecutive series
      of 84 carotid endarterectomies done by a single surgeon and commenced under
      regional anaesthesia with sedation was studied. There were 54 men and 27 women
      (three bilateral procedures), with a median age of 71 years (range 48-87 years).
      All patients had carotid stenosis > 70% 80 procedures were done for symptomatic
      disease and three asymptomatic patients were treated before cardiac surgery (one
      bilateral). RESULTS: Seventy-seven procedures were completed under regional
      anaesthesia and sedation alone; seven required conversion to general anaesthetic,
      usually for intolerance of the operation. An intraoperative shunt was required on
      only four occasions (5%). Postoperatively eight patients required critical care
      monitoring, usually for blood pressure control. The remainder were nursed on the
      vascular ward, and 68% were discharged home on the day after surgery. No patient
      died, but there were two neurological complications. One patient had a cerebellar
      stroke 10 days after surgery, but recovered fully after 4 months. A second
      developed cerebral oedema due to severe intraoperative hypertension and required
      intensive care for 15 days. He too recovered fully. Five patients had a further
      episode of transient cerebral ischaemia within 1 month of operation, but in all
      cases duplex imaging showed a widely patent carotid and there were no sequelae.
      CONCLUSION: Target controlled propofol infusion is an effective method of
      sedation in patients undergoing carotid endarterectomy.

PMID- 15972044
TI  - POSSUM scoring for laparoscopic cholecystectomy in the elderly.
AB  - BACKGROUND: Physiological and operative severity score for the enumeration of
      mortality and morbidity (POSSUM) scoring is a validated scoring system in the
      audit of surgical outcomes; however, evaluation of this system has mostly been
      applied to open surgical techniques. The present study examines the validity of
      POSSUM in predicting morbidity and mortality in patients undergoing laparoscopic
      cholecystectomy (LC) with the recognized risk factor for postoperative mortality
      of advanced age. METHODS: All patients aged 80 years or over undergoing LC in one
      surgical unit between January 1993 and December 1999 were identified from the
      surgical operations database of the hospital. Case-note review was used to
      collate data in terms of clinical and operative factors as described in POSSUM.
      Observed/POSSUM estimated (O/E) ratio of morbidity and 30-day mortality were
      calculated. RESULTS: Laparoscopic cholecystectomy was performed in 76 patients
      aged 80 years or over during the study period. Of these patients, case notes for
      70 patients (92%) were available for review. Median (range) age was 83 years (80
      93 years) and median (range) American Society of Anesthesiologists score was 2 (2
      4). Twenty-six (34%) of 70 patients underwent cholecystectomy during an acute
      admission. The mean physiology severity score was 23 and operative severity
      score, 8. A significant postoperative morbidity was observed in 15 (22%) of 70
      patients. There was no 30-day mortality. Using exponential analysis, POSSUM
      predicted morbidity in 15 patients and mortality in seven patients. Thus, O/E
      ratios for morbidity and mortality were 1 and 0, respectively. CONCLUSION: POSSUM
      scoring performs well in predicting morbidity, but overpredicts mortality, after
      LC in patients aged over 80 years. An assessment of its application to other
      laparoscopic procedures merits evaluation.

PMID- 15972045
TI  - Randomized prospective controlled trial of lateral internal sphincterotomy versus
      injection of botulinum toxin for the treatment of idiopathic fissure in ano.
AB  - BACKGROUND: Chronic anal fissure is a significant cause of morbidity. Internal
      sphincterotomy has long been the operative treatment of choice. Concerns remain,
      however, on its effects on continence. Botulinum toxin has been used as an agent
      for chemical sphincterotomy, causing temporary alleviation of sphincter spasm and
      allowing the fissure to heal. The aim of the present study was to compare the
      results of sphincterotomy to botulinum toxin. METHODS: The study was designed as
      a randomized controlled trial. All adult patients over the age of 18 with chronic
      idiopathic fissure in ano who had failed conservative treatment were included in
      the trial. Patients were randomized to receive either Botox or sphincterotomy.
      Pain, healing of fissure and continence scores were the outcomes assessed.
      RESULTS: A total of 38 patients were studied. Seventeen patients were randomized
      to receive Botox and 21, sphincterotomy. Patients in the Botox group were found
      to have significantly higher 2-week pain scores and reoperation rates, and poor
      healing. Continence scores were not significantly different in the two groups.
      CONCLUSION: Sphincterotomy gives better results than Botox in the treatment of
      fissure. Botox, however, is safe with no complications and no detriment to
      continence and could be used in certain situations.

PMID- 15972046
TI  - Skin antiseptics and the risk of operating theatre fires.
AB  - BACKGROUND: Following press reports of patients catching fire or receiving
      chemical burns in the operating theatre, a review was conducted on the
      flammability of skin antiseptics. The purpose of the paper was to clarify
      confusion regarding povidine-iodine (Betadine), which had been reported as being
      flammable, and also to determine the use of alcohol-based solutions in the Hunter
      Area Health Service. A risk assessment was conducted and risk reduction
      strategies outlined. METHODS: Risk assessment was made following a literature
      review and an audit of 10 operating theatres in the Hunter Area Health Service.
      RESULTS: Risk for operating room fires from alcohol-based skin antiseptics was
      confirmed. Antiseptics in aqueous solutions only smoulder. The Hunter Health
      survey indicated that although alcohol-based solutions were not used in operating
      theatres, they were used in anaesthetic bays for insertion of epidural and
      central line catheters. Strategies to reduce the risk of fire include
      discontinuation of use of alcohol-based skin antiseptics in operating theatres;
      using fire retardant surgical drapes; installing over-current protection devices
      on electrical equipment; minimizing flammable conditions by avoiding nitrous
      oxide and using the lowest required concentration of inspired oxygen; use of non
      flammable cuffed endotracheal tubes; education and training of operating theatre
      personnel in fire hazards. CONCLUSIONS: Operating theatre fires continue to be a
      major risk for patient safety. In order to reduce this risk, the strategies
      outlined here should be followed.

PMID- 15972047
TI  - Gall bladder injuries as part of the spectrum of civilian abdominal trauma in
      South Africa.
AB  - BACKGROUND: Trauma to the gall bladder is rare, but when missed or improperly
      managed it may be associated with significant morbidity. The aim of the present
      study was to review the management and outcomes of gall bladder trauma in a
      trauma centre. METHODS: Forty-three patients with gall bladder injury due to
      abdominal trauma were reviewed over a 3-year period. Surgical management,
      associated injuries, morbidity and mortality rates were determined. RESULTS:
      Among 1242 patients undergoing laparotomy for acute trauma, 43 patients (3.46%)
      with gall bladder injuries were identified. Forty patients sustained penetrating
      injuries (37 with gunshot wounds and three with stab wounds), and three patients
      suffered from blunt trauma. All patients with gall bladder injury underwent
      abdominal exploration because of associated intra-abdominal injuries. Thirty-six
      patients were treated with cholecystectomy, four patients underwent primary
      suture repair of the gall bladder perforation, while three patients with gall
      bladder injury were treated without any surgical intervention at laparotomy. No
      complications could be attributed to the gall bladder trauma or surgery.
      CONCLUSION: Cholecystectomy is the preferred procedure of choice for gall bladder
      injuries and is associated with no morbidity.

PMID- 15972048
TI  - Mini-laparoscopic cholecystectomy in children under 10 years of age with sickle
      cell disease.
AB  - BACKGROUND: Cholelithiasis is very common in patients with sickle cell disease
      (SCD) and is responsible for recurrent attacks of abdominal pain. The ideal
      management, especially for children, remains controversial. The purpose of the
      present study was to evaluate the safety and outcome of mini-laparoscopic
      cholecystectomy (MLC) in young children under age of 10 years with SCD. METHODS:
      A prospective study was carried out of 75 children with SCD under 10 years of age
      with recurrent abdominal pains seen between August 2001 and March 2004 at Armed
      Forces Hospital, Khamis Mushayt, Saudi Arabia, who were screened for
      cholelithiasis. Twelve (16%) of the 75 children were found to have gallstones.
      The mean age was 7.8 years (range 4-9 years). All 12 children underwent MLC.
      Anaemia was corrected preoperatively in all the patients. Operative time,
      intraoperative complications, hospital stay, and postoperative recurrent
      abdominal pain were recorded. RESULTS: The mean operating time was 46.5 min
      (range: 35-65 min). Intraoperative cholangiogram failed in two children due to
      narrow cystic ducts. The mean hospital stay was 2.1 days (range: 2-4 days). No
      patient required intra-abdominal drain. The mean follow-up period was 13.4 months
      (range: 4-24 months). The only postoperative complication was deep jaundice 1
      month postoperatively due to cholestasis, and this responded to medical
      treatment. None of the children had recurrent abdominal pain after MLC.
      CONCLUSION: Mini-laparoscopic cholecystectomy is a safe surgical procedure for
      the management of cholelithiasis in children with SCD and leads to improvement in
      the quality of life by decreasing the frequency of recurrent abdominal pain.

PMID- 15972049
TI  - Breast cancer in young Asian women: study on survival.
AB  - BACKGROUND: Breast cancer in young patients is often associated with a poorer
      prognosis, but there has been a paucity of published data in an Asian population.
      METHODS: One hundred and six patients (12.6%) under the age of 40 years with
      breast cancer (group V) were compared with 737 patients with breast cancer aged
      40 years or more (group W). Demographics, presentations, pathological profiles,
      treatment and survival measures were analysed. RESULTS: Median tumour size was
      similar in both groups. Group V had more patients with grade 3 tumours and nodal
      involvement compared to group W (51.5% vs 38.1%, P = 0.012 and 52.5% vs 41.8%, P
      = 0.045). The mean Nottingham prognostic index (NPI) score was significantly
      higher in group V compared to group W (4.75 vs 4.26, P < 0.001). The incidences
      of chemotherapy and radiotherapy in group V were higher than group W (69.2% vs
      35.2%, P < 0.001 and 41.1% vs 24.4%, P = 0.002). There were no differences in
      overall survival and disease-free survival (local recurrence). CONCLUSION:
      Patients below 40 years with breast cancer have tumours with a poorer prognostic
      profile. However, this did not translate into a poorer overall survival, and this
      might be attributable to more aggressive adjuvant treatment of younger patients.

PMID- 15972050
TI  - Evaluation of fresh frozen plasma usage at a tertiary care hospital in North
      India.
AB  - BACKGROUND: Concerns regarding transfusion-transmitted infections and non
      availability of blood components in developing nations, make it crucial to
      optimize fresh frozen plasma (FFP) transfusions and reduce wastage. METHODS: A
      concurrent prospective study of FFP usage was carried out in a tertiary care
      hospital in north India. RESULTS: A total of 595 units were issued to 112
      patients during the study period, of which 53 units (8.9%) were returned to the
      blood centre unused, leading to wastage. Appropriate indications for FFP usage
      were as per accepted British Council for Standardization in Haematology (BCSH)
      criteria. Among 112 patients 33 (29.5%) had had appropriate FFP transfusions (205
      units) for indications that primarily included chronic liver disease,
      disseminated intravascular coagulopathy and prolonged bleeding with abnormal
      coagulation profile. Out of 33 patients with appropriate indications, 24 had
      abnormal coagulation profile but only half of these patients (n = 12) received
      adequate dose of FFP. Fresh frozen plasma was used for inappropriate indications
      in 79 patients (70.5%), which mainly included bleeding following cardiac surgery
      with normal coagulation test results, hypovolaemia and hypoproteinaemia. Such
      misuse was higher in surgical units than medical services (78 vs 45%).
      CONCLUSION: Fresh frozen plasma is grossly misused even in resource-deficient
      nations and immediate intervention is needed to stem the flow of this component.
      Physician education programmes and a monitoring system to ensure strict adherence
      to the established guidelines are required to reduce undue waste of this blood
      component.

PMID- 15972051
TI  - Role of fenestration and resection for symptomatic solitary liver cysts.
AB  - BACKGROUND: Symptomatic liver cysts can be managed surgically by fenestration or
      by hepatic resection. The present study was designed to investigate the current
      role of each surgical technique in the management of this benign condition.
      METHODS: Forty consecutive patients with symptomatic liver cyst (non-parasitic
      and non-malignant) surgically treated by fenestration or resection were
      identified from a prospectively collected database. An analysis of primary
      outcome measures including operative parameters, morbidity and mortality rates,
      length of postoperative stay and recurrence rates in months was carried out.
      RESULTS: The laparoscopic fenestration group had the best perioperative outcome.
      At median follow up of 20 months, there were no recurrences in the resection
      group but recurrence occurred in 6/27 (22%) in the fenestration group. Four of
      these recurrences were asymptomatic and were managed conservatively while two
      symptomatic recurrences required a resection. CONCLUSION: Laparoscopic
      fenestration is the best treatment for symptomatic liver cysts as the primary
      operation. It is associated with the lowest blood loss, lowest morbidity and
      shortest hospital stay. Liver resection is best reserved for recurrent
      symptomatic cysts and cystic lesions suspicious of tumours where it can be safely
      performed and associated with a zero recurrence rate.

PMID- 15972052
TI  - Pancreatic and duodenal injuries: keep it simple.
AB  - BACKGROUND: The management of pancreatic and duodenal trauma has moved away from
      complex reconstructive procedures to simpler methods in keeping with the trend
      towards organ-specific, damage control surgery. METHOD: A retrospective case note
      review was undertaken over a 30-month period to evaluate a simplified protocol
      for the management of these injuries. RESULTS: Of 100 consecutive patients there
      were 51 with pancreatic injury, 30 with a duodenal injury and 19 with combined
      pancreaticoduodenal trauma. Overall mortality was 18.0%, with a late mortality
      (after 24 h) of 9.9%. This is comparable to previous studies. Morbidity from
      abscesses, fistulas and anastomotic breakdown was acceptably low. CONCLUSION: The
      concept of staged laparotomy can be successfully applied to wounds of the
      pancreas and duodenum. Debridement of devitalized tissue and drainage can be
      employed for most cases of pancreatic trauma. Most duodenal injuries can be
      managed with debridement and primary repair. Temporary exclusion and reoperation
      should be employed for unstable patients.

PMID- 15972053
TI  - Prioritization of cataract surgery: visual analogue scale versus scoring system.
AB  - BACKGROUND: The purpose of the present paper was to evaluate the variability of
      using a visual analogue scale (VAS) and to assess the feasibility of a priority
      setting scoring system for prioritizing elective cataract surgery. METHODS:
      Consecutive cases listed for cataract surgery were prospectively recruited.
      Ophthalmologists listed patients to undergo early or normal surgery and were
      asked to rate the urgency of surgery using a VAS. Patients were then reassessed
      and a cataract surgery prioritization (CSP) score was calculated based on the New
      Zealand priority criteria for cataract surgery. Correlation coefficients between
      VAS and CSP scores were calculated to determine the variability among
      ophthalmologists in using the VAS in prioritizing surgery. Further analyses were
      performed to assess the potential impact of implementing the CSP system. RESULTS:
      A total of 326 patients were recruited. There was a positive correlation between
      VAS and CSP scores (Spearman rho= 0.407, P < 0.001). A high degree of variation
      among ophthalmologists in the use of VAS was found. Patients with poor binocular
      vision were not listed as early, whereas patients with poor vision in the eye
      listed for cataract surgery but good vision in the fellow eye were more likely to
      be prioritized to have early operation. These findings suggest that patients with
      severe impairment in binocular visual function were not adequately accounted for
      during cataract surgery listing. CONCLUSIONS: The use of a VAS for prioritizing
      cataract surgery may be suboptimal due to high subjectivity. Adoption of an
      objective criteria-validated priority-setting scoring system may allow better
      stratification of patients to ensure better service provision.

PMID- 15972054
TI  - Oncological outcome of 100 laparoscopic radical nephrectomies for clinically
      localized renal cell carcinoma.
AB  - BACKGROUND: Laparoscopic renal surgery is now accepted within the urological
      community and its indication is extended to oncological operation. The
      oncological outcome and survival of patients undergoing laparoscopic radical
      nephrectomy for clinically localized renal cell carcinoma were evaluated.
      METHODS: From October 1998 to July 2003, 100 patients underwent laparoscopic
      radical nephrectomy for clinically localized renal cell carcinoma. All operations
      were performed by transperitoneal approach with early vascular control.
      Perioperative events and pathological data were recorded prospectively. Patients
      were followed up by clinical examination, chest radiograph, ultrasonography
      and/or computed tomography where appropriate. RESULTS: The median age of patients
      was 61 years. Median operating time was 120 min and blood loss was 100 mL. There
      were five open conversions. There was no perioperative mortality but 11 patients
      had complications. Resection margins were clear in all but one patient. The
      median tumour size was 4.6 cm. The median follow-up time was 30 months. All
      patients survived up to the date of review. No patient developed port-site
      recurrence but two patients had recurrence at the renal bed 1 year after the
      operation. Five patients developed distant metastases involving liver, lung and
      bone. CONCLUSION: Laparoscopic radical nephrectomy is a safe and efficacious
      treatment option for clinically localized renal cell carcinoma. The intermediate
      term oncological outcome appears favourable.

PMID- 15972055
TI  - Post-pneumonectomy empyema: current management strategies.
AB  - Post-pneumonectomy empyema is an uncommon but potentially life-threatening
      complication. It has a strong association with bronchopleural fistula, which acts
      as a continued source of infection into the thoracic cavity. Numerous risk
      factors have been identified and strategies formulated to minimize its
      occurrence. When bronchopleural fistula occurs, its treatment depends on several
      factors including extent of dehiscence, degree of pleural contamination and
      general condition of the patient. Early diagnosis and assessment with appropriate
      investigations, and aggressive therapeutic strategies are paramount in
      controlling sepsis, facilitating closure of fistula, and sterilization of the
      closed pleural space. Recent success with repeat debridement has made routine
      space obliteration not mandatory in management. The development of minimal-access
      interventions including video-assisted thoracic surgery, endoscopic application
      of tissue glue and stenting may be additional tools to complement conventional
      surgery in post-pneumonectomy empyema management.

PMID- 15972056
TI  - Evolution of trends in risk management.
AB  - In the past, the detection and response to adverse clinical events were viewed as
      an inherent part of professionalism; and, if perceived problems were not sorted
      out at that level, the ultimate expression of dissatisfaction was litigation.
      There are now demands for the adoption of more transparent and effective
      processes for risk management. Reviews of surgical practice have highlighted the
      presence of unacceptable levels of avoidable adverse events. This is being
      resolved in two ways. First, attention is being directed to the extent that
      training and experience have on outcomes after surgery, and both appear to be
      important. Second, a greater appreciation of human factors engineering has
      promoted a greater involvement of surgeons in processes involving teamwork and
      non-technical skills. The community wants surgeons who are competent and health
      care systems that minimize risk. In recent times attention has been focused on
      the turmoil associated with change; but, when events are viewed over a period of
      several decades, there has been considerable progress towards these ideals.
      Further advancement would be aided by removing the adversarial nature of
      malpractice systems that have failed to maintain standards.

PMID- 15972057
TI  - Effect of amrinone on mucosal permeability in experimental intestinal
      ischaemia/reperfusion injury.
AB  - BACKGROUND: The preventive effect of amrinone on ischaemia/reperfusion (I/R)
      injury has been shown in the medical literature. The purpose of the present study
      was to investigate the preventive effect of amrinone on I/R injury of the small
      bowel of the rat. METHODS: Thirty-two Wistar albino rats (140-180 g) were divided
      into four groups (n = 8). In all groups except the sham group the superior
      mesenteric artery was clamped for 30 min. At the beginning of reperfusion, 1 mL
      of 2405 Bq/mL 51Cr-ethylenediamine tetra-acetic acid (EDTA) was administered into
      the prepared ileal segment. Following 30 min of reperfusion, 1 mL of blood was
      obtained from the portal vein. After the rats were killed, the small intestine
      was removed for histopathological studies. A total of 5 mg/kg amrinone was
      administered to the rats in group 1 before ischaemia and in group 2 before
      reperfusion, whereas only saline was administered to the rats in the control
      group. Statistical analysis was carried out with Kruskal-Wallis and chi2 test, P
      < 0.01 was considered significant. RESULTS: Both the blood 51Cr-EDTA measurements
      (mean +/- SD) and mucosal injury grades (MIG) were highest in the control group
      (3.95 +/- 0.71 c.p.m.; MIG, 3-5) followed by group 2 (0.50 +/- 0.35 c.p.m.; MIG,
      1-3), group 1 (0.47 +/- 0.34 c.p.m. MIG, 0-3), and sham group (0.12 +/- 0.05
      c.p.m.; MIG, 0). The difference between groups 1 and 2 and the control group were
      statistically significant (P < 0.01 for each comparison). The results of group 1
      and 2 were similar statistically (P > 0.05). CONCLUSIONS: Amrinone was found to
      be effective in preventing intestinal I/R injury.

PMID- 15972058
TI  - Late complication following coil embolization of a biliary leak.

PMID- 15972059
TI  - Warts in the oesophagus: a potentially fatal but curable carcinoma.

PMID- 15972060
TI  - Cardiac tamponade during central venous vascular access port insertion.

PMID- 15972061
TI  - Chylous ascites and jejunal carcinoid: a diagnostic challenge.

PMID- 15972062
TI  - Rare case of benign multicystic peritoneal mesothelioma.

PMID- 15972063
TI  - Management of blunt splenic trauma.

PMID- 15972065
TI  - Medical decision making: a selective review for child psychiatrists and
      psychologists.
AB  - Physicians, including child and adolescent psychiatrists, show variability and
      inaccuracies in diagnosis and treatment of their patients and do not routinely
      implement evidenced-based medical and psychiatric treatments in the community. We
      believe that it is necessary to characterize the decision-making processes of
      child and adolescent psychiatrists using theories and methods from cognitive and
      social sciences in order to design effective interventions to improve practice
      and education. This paper selectively reviews the decision-making literature,
      including recent studies on naturalistic decision making, novice-expert
      differences, and the role of technology on decision making and cognition. We also
      provide examples from other areas of medicine and discuss their implications for
      child psychiatry.

PMID- 15972066
TI  - Family-based services in children's mental health: a research review and
      synthesis.
AB  - A systematic review was undertaken of scientifically rigorous studies of family
      based services in children's health and mental health. From a pool of over 4000
      articles since 1980 in health and mental health that examined either specific
      family-based interventions for families of children or the processes of
      involvement, 41 studies were identified that met the methodological criteria for
      inclusion. These 41 studies encompassed 3 distinct categories: families as
      recipients of interventions (e.g., family education, support, engagement,
      empowerment); (b) families as co-therapists; and (c) studies of the processes of
      involvement (e.g., therapeutic alliance, engagement, empowerment, expectancies,
      and choice). Too few experimental studies exist to conclude decisively that
      family-based services improve youth clinical outcomes. However, those studies
      that have been rigorously examined demonstrate unequivocal improvements in other
      types of outcomes, such as retention in services, knowledge about mental health
      issues, self-efficacy, and improved family interactions - all outcomes that are
      essential ingredients of quality care. Four implications are drawn from this
      review. (1) Effective family education and support interventions from studies of
      adults with mental illnesses and from studies of families of high-risk infants
      exist and can be imported into the field of children's mental health. (2) The
      range of outcomes that are typically assessed in clinical treatment studies is
      too narrow to afford an adequate view of the impact of family-based
      interventions. A broader view of outcomes is needed. (3) The absence of a robust
      literature on process variables other than therapeutic alliance limits
      conclusions about how and why interventions are effective. Attention to the
      processes by which families become involved in services will require a more
      robust and nuanced range of studies that attend simultaneously to processes of
      change and to outcome improvement. (4) Linkage of effective family-based
      interventions to delivery of evidence-based services is likely to amplify the
      impact of those services and improve outcomes for youth and families.

PMID- 15972067
TI  - The stigmatization of mental illness in children and parents: developmental
      issues, family concerns, and research needs.

PMID- 15972068
TI  - Review of the efficacy and safety of antidepressants in youth depression.
AB  - BACKGROUND: Depression in children and adolescents is a cause of substantial
      morbidity and mortality in this population. It is a common disorder that affects
      2% of children and up to 6% of adolescents. Although antidepressants are used
      frequently for the treatment of this disorder, there has been recent controversy
      about the efficacy and safety of these medications in this population. This
      review examined the available evidence from clinical trials of antidepressants in
      adolescents and children with depression. METHODS: Clinical trial data reviewed
      were obtained from published reports, including peer review journals and meeting
      abstracts, as well as unpublished data in the public domain. Clinical trials in
      this review included large RCTs of antidepressants in youth under the age of 19
      with depression. Studies were identified in 2 stages: 1) all RCTs included in the
      2004 FDA safety report were reviewed; and 2) to ensure that no additional studies
      not reported to the FDA were missed, MEDLINE and PSYCH Info were searched from
      inception until December 2004. A total of 8 published studies and 9 unpublished
      studies were identified and reviewed. RESULTS: Efficacy and safety results from
      each study are reviewed in detail. There are significant differences in remission
      and response rates between different antidepressants but also between placebo
      groups across studies. Adverse events are common in clinical trials involving
      children and adolescents with depression. Due to lack of access to full data
      sets, effect sizes could not be calculated. CONCLUSIONS: With the variability in
      trial methodology and the variation in the drug/placebo response rates within a
      single trial, clinicians need to be judicious in their interpretation of research
      data on pediatric antidepressant trials. Significant methodological issues may
      also have affected the efficacy and safety results from these clinical trials.

PMID- 15972069
TI  - The impact of preschool inattention, hyperactivity, and impulsivity on social and
      academic development: a review.
AB  - The literature on the prevalence and stability of preschool problems of
      inattention, hyperactivity, and impulsivity suggests a number of links to early
      literacy skills and broader school achievement. Developmental considerations in
      the assessment of preschool ADHD are reviewed in this paper, along with evidence
      for the stability of symptoms over time and the relationship between early
      symptoms of ADHD and elementary school achievement. Emphasis is placed on
      describing the nature of the connection between preschool ADHD symptoms and
      academic achievement, as few studies to date have focused specifically on that
      relationship. Several explanations for the relationship between preschool ADHD
      symptoms and achievement are analyzed, including an explanation that focuses on
      the relationship between inattention, hyperactivity, and impulsivity and the
      acquisition of emergent literacy and language skills. Finally, the evidence for
      four models that have been proposed to account for the link between behavior and
      learning is reviewed and critically analyzed. Suggestions are made for future
      research that might resolve important questions only partially addressed in
      studies to date.

PMID- 15972070
TI  - Are endophenotypes based on measures of executive functions useful for molecular
      genetic studies of ADHD?
AB  - BACKGROUND: Behavioral genetic studies provide strong evidence that attention
      deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet,
      due to the complexity of the ADHD phenotype, questions remain as to the specific
      genes that contribute to this condition as well as the pathways from genes to
      behavior. Endophenotypes, or phenotypes that are more closely linked to the
      neurobiological substrate of a disorder, offer the potential to address these two
      issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential
      endophenotypes for ADHD have not been systematically studied. METHOD: The current
      paper reviews evidence supporting the use of deficits on neurocognitive measures
      of executive functions for this purpose. RESULTS: Such deficits are a correlate
      of ADHD and show preliminary evidence of heritability and association with
      relevant candidate genes. Nonetheless, studies that have assessed the familial
      and genetic overlap of neurocognitive impairments with ADHD have yielded
      inconsistent results. CONCLUSIONS: In order for executive function deficits to be
      used as an endophenotype for ADHD, we recommend greater attention to the
      neurocognitive heterogeneity of this disorder and to the precision of measurement
      of the neuropsychological tests employed. We also discuss empirical strategies
      that may be necessary to allow such research to progress prior to full resolution
      of the pathophysiological basis of ADHD.

PMID- 15972073
TI  - Pre-ovulatory temperature gradients within mammalian ovaries: a review.
AB  - The existence of a temperature gradient between the testis and deep body
      temperature has been accepted for many years. It is based on two simultaneous
      principles: cooling of the testis through the scrotal wall and transfer of heat
      between the testicular blood vessels. The ovary is positioned in the abdomen; a
      temperature difference parallel to the male system therefore seems less likely.
      However, the temperature of large follicles has been found to be 0.5 to 1.5
      degrees C cooler than the ovarian stroma in rabbits, pigs and, probably, women.
      The temperature difference seems to be based on a heat-consuming process in the
      expanding follicullar fluid, and a local transfer of heat between intra-ovarian
      blood vessels. The reason for the temperature gradient is not yet known; one may
      speculate of a common reason for the cooling of the gamete in male and female.

PMID- 15972074
TI  - Efficiency of Echinacea purpurea on performance and immune status in pigs.
AB  - The aim of the present investigation was to examine the inclusion of the dried
      herb Echinacea purpurea (L.) MOENCH as feed additive in diets of sows, piglets,
      and grower/finisher pigs on growth performance, blood picture, plasma enzymes
      including proliferation of lymphocytes, antibody status, and protein and immune
      globulin content of colostrum. The control groups were supplemented with alfalfa
      meal. The sows (total 36) received 0%, 1.2%, or 3.6% Echinacea cobs in the diet
      from day 85 to day 110 of gestation and 0%, 0.5%, or 1.5% Echinacea cobs up to
      day 28 of lactation. No significant differences were found for growth
      performance, weight loss, blood picture, plasma enzymes, and colostrum
      composition. Performance of the sucking piglets was not impaired either during
      lactation or during a 4 week observation period after weaning. The health status
      was similar in all treatment groups. In a second experiment, lasting 6 weeks,
      with 36 piglets (5.8-22.1 kg body weight), 1.8% Echinacea cobs, or 20 mg/kg feed
      Flavomycin were supplemented. No significant differences were found for the
      recorded parameters. Feed conversion ratio (kg feed/kg gain) of the Echinacea
      group was slightly (4%) increased (1.54 vs. 1.60). In a third trial, 48
      grower/finisher pigs were used during a 9-week experimental period with two
      supplementation phases (weeks 1-3 and weeks 7-9). The experimental groups
      received 0%, 1.5% cobs or 4-6 ml pressed juice (commercial standard) per day
      respectively. Vaccination with Swine erysipelas was implemented in weeks 1 and 5
      to determine the specific immune response. Growth performance and blood picture
      for all groups were similar, however, feed conversion of both Echinacea
      supplemented groups was significantly (p < 0.03) better than of the
      unsupplemented control group (2.44 vs. 2.51). In addition, the Swine erysipelas
      antibodies showed a marked significance (p < 0.05) in regard of altitude in both
      supplemented groups. It is concluded, that E. purpurea might be used as a feed
      additive to achieve immune stimulating efficiency in pig production and increase
      feed-to-gain-conversion. The efficiency of cobs is comparable to a commercial
      juice product.

PMID- 15972075
TI  - Effect of short chain fatty acids infused intraileally on interdigestive exocrine
      pancreatic secretions in growing pigs.
AB  - The effect of intraileally infused short chain fatty acids (SCFA) and saline as
      control on the exocrine pancreatic secretions during the interdigestive phase was
      studied using three 8-weeks-old piglets. Pigs were surgically fitted with a
      pancreatic duct catheter, re-entrant duodenal T-cannula for collection and
      subsequent return of pancreatic juice, and with an infusion T-cannula at the
      distal ileum. Saline as control, 5.0 and 10.0 mm butyrate, 7.5 and 15.0 mm
      propionate and 85.0 and 170.0 mm acetate were infused at 2 ml/kg body weight (BW)
      for 30 min into the ileum of overnight fasted piglets via ileal T-cannula. The
      calculated volume of infusates was administrated in five equal bolus at 6 min
      intervals over a period of 30 min. The pancreatic juice was collected 60 and 30
      min before and 30, 60, 90 and 120 min after the start of infusion. The trypsin (p
      = 0.07, p > 0.15 respectively) and protein (p > 0.15, p = 0.05 respectively)
      outputs immediately decreased after the infusion of acetate at the dose of 85.0
      and 170.0 mm, respectively, whereas pancreatic juice outflow (p > 0.15) was not
      significantly affected when compared with levels 30 min before infusion. After
      the infusion of butyrate at the dose of 5.0 mm, trypsin (p = 0.01) and protein (p
      = 0.12) outputs increased immediately whereas pancreatic juice outflow was not
      affected (p > 0.15) in comparison with levels 30 min before infusion. No
      significant differences were observed after infusion of butyrate at the dose of
      10 mm for the pancreatic juice outflow, trypsin and protein outputs when compared
      with the level before infusion, although these values were numerically lower
      immediately after the infusion. The pancreatic juice outflow increased (p = 0.03)
      after the infusion of propionate at the dose of 7.5 mm and decreased (p = 0.005)
      immediately after the infusion of propionate at the dose of 15.0 mm when compared
      with the levels 30 min before the infusions. After the infusion of propionate at
      the dose of 7.5 or 15.0 mm for the output of protein and trypsin, no significant
      differences (p > 0.15) were observed when compared with levels 30 min before
      infusion. In summary, the intraileal infusion of SCFA at different doses exerts a
      short-term and moderate effect on the interdigestive exocrine pancreatic
      secretions in pigs.

PMID- 15972076
TI  - Effects of long-term growth hormone-releasing factor treatment on growth, feed
      conversion efficiency and dry matter intake in growing female buffaloes (Bubalus
      bubalis).
AB  - Effects of long-term growth hormone-releasing factor (GRF) on growth performance,
      feed conversion efficiency (FCE) and dry matter intake (DMI) were studied in
      growing buffaloes. Twelve female Murrah buffaloes of 6-8 months of age were
      divided into two groups of six each on the basis of their body weights so that
      the average body weights of the groups did not differ (p > 0.05). Animals of each
      group were administered intravenously with either sterile distilled water
      (control group) or equal volume of GRF solution containing 10 mug GRF (1-44)
      NH2/100 kg body weight (treatment group) at fortnight interval from week 6 (5
      week pre-treatment period) for 36 weeks (weeks 6-42 treatment period). Thereafter
      a 10-week post-treatment period was added. All the animals were weighed
      consecutively 2 days in a week and the average body weight of the two
      observations in the week was thus considered for further calculation. Dry matter
      intake was recorded daily. Average daily gain, FCE and DMI/100 kg body weight
      were also calculated. Plasma progesterone was estimated in the samples collected
      twice a week at 3-4-day intervals to assess whether either group had begun
      ovarian cycles. It was found that ADG and FCE were higher (p < 0.01) in GRF
      treated animals during treatment and even 10-week post-treatment period.
      Interestingly, total DMI was not different (p > 0.05) between the groups during
      treatment period but found to be lower in GRF treated animals during post
      treatment period. The DMI/100 kg body weight was lower (p < 0.01) in GRF-treated
      animals during treatment and even after cessation of treatment for 10 weeks. The
      GRF administration for long-term increased (p < 0.05) plasma progesterone. Plasma
      progesterone concentrations suggest that no animal from either group reached
      puberty till the end of the experiment. In conclusion, repeated GRF
      administration for longer term decreased (p < 0.01) DMI/100 kg body weight and
      increased (p < 0.01) FCE and enabled the animals to grow faster.

PMID- 15972077
TI  - Kinetics and metabolism of zearalenone in young female pigs.
AB  - The fate of a single bolus of the Fusarium mycotoxin zearalenone (ZON) given
      intravenously to pigs was followed up. Pigs were equipped with duodenal re
      entrant cannulas, post-valvular T-shape cannulas and with a urinary bladder
      balloon catheter. The animals were divided into three groups. Pigs of the control
      group were injected with ZON (Co), and pigs of the second group were also
      injected with ZON but their duodenal digesta was quantitatively exchanged for 12
      h with corresponding pigs of the third group, not injected with ZON. Therefore,
      the second group had a disrupted entero-hepatic cycling of ZON (DEHC) and the
      third one had an induced entero-hepatic cycling of ZON (IEHC). The kinetic
      profile of ZON and its metabolites in plasma and their flow with urine, duodenal
      and ileal digesta and with faeces was examined over the next 72 h after the bolus
      was given. Eleven days later, pigs were slaughtered for collection of bile, urine
      and liver to analyse ZON residues. In all specimens examined, alpha-zearalenol
      (ZOL) was detected as the only metabolite of ZON. Kinetic evaluation of the
      plasma data revealed that the terminal elimination half-life of ZON was reduced
      from 2.63 h in pigs of Co-group to 1.1 h when EHC of ZON was disrupted for 12 h
      (DEHC-group). The maximum ZON concentration in plasma of pigs with the IEHC was
      found at 2.73 h after the bolus was given to their counterparts. The percentage
      of the alpha-ZOL- and ZON-area under the curves (AUC) estimated for the IEHC
      group amounted to approximately 18% of the corresponding AUC of the Co-group
      which would suggest that a substantial proportion of both substances are re
      cycled via entero-hepatic re-circulation. Cumulative recovery of ZON and alpha
      ZOL, expressed as percentage of the ZON-bolus was characterized by a saturation
      kinetics in urine and duodenal digesta, and after 72 h, the respective values for
      Co-, DEH-, and IEHC-groups were 70%, 55% and 12%; and 35%, 22% and 11%. Faecal
      excretion started to increase steeply after 48 h and still continued to increase
      after 72 h when the cumulative excretion was 6%, 3% and 2% for Co-, DEHC- and
      IEHC-groups respectively. Fourteen days after the bolus injection, ZON and alpha
      ZOL concentrations in bile, liver and urine were lower than the detection limits
      of the applied method. The results would suggest that within this period of time
      a massive single bolus of ZON is nearly completely eliminated from the body.

PMID- 15972078
TI  - Effect of dietary L-carnitine supplementation on growth performance of piglets
      from control sows or sows treated with L-carnitine during pregnancy and
      lactation.
AB  - Previous studies showed that supplementation of sows' diets with L-carnitine
      increases body weights of their piglets at birth. This study was performed to
      investigate whether piglets of sows treated with L-carnitine differ in their
      growth potential from that of piglets of untreated control sows after weaning. It
      was also investigated whether supplementation of piglets' diets with L-carnitine
      improves their growth after weaning. In two trials, piglets of the first litters
      of primiparous sows (trial 1) and the second litters of the same sows (trial 2)
      were divided into four groups: group 1, piglets of control sows, fed a control
      diet; group 2, piglets of control sows fed a diet supplemented with 30 mg L
      carnitine/kg; group 3, piglets of L-carnitine-treated sows, fed a control diet;
      group 4, piglets of L-carnitine-treated sows fed a diet supplemented with 30 mg L
      carnitine/kg. Mean initial body weights of the piglets of the four groups were
      identical. They were 8.5 kg in trial 1 and 12.5 kg in trial 2. Diets were fed ad
      libitum over a period of 35 days. Piglets from sows treated with L-carnitine did
      not differ in body weight gains, feed intake and gain : feed ratio from those of
      control sows. In trial 1, piglets supplemented with L-carnitine had higher body
      weight gains (p < 0.005) and showed a tendency towards a higher gain : feed ratio
      (p = 0.09) than piglets fed the control diets. In trial 2, no significant
      difference in these parameters emerged between piglets fed the diet supplemented
      with L-carnitine and those fed the control diet. In conclusion, this study shows
      that dietary L-carnitine treatment of sows does not improve the growth potential
      of their piglets after weaning under the conditions of equal initial body
      weights. The study also shows that L-carnitine supplementation of their diets
      improves the growth performance in light piglets of primiparous sows.

PMID- 15972079
TI  - Influence of myristic acid supplementation on energy, fatty acid and calcium
      metabolism of sheep as affected by dietary calcium and forage : concentrate
      ratio.
AB  - In a 6 x 6 Latin square arrangement, sheep of 41 kg body weight were fed myristic
      acid [C14:0; 50 g/kg dry matter (DM)] supplemented to two basal diets of forage :
      concentrate ratios of 1 : 1.5 and 1 : 0.5 and adjusted to dietary calcium (Ca)
      contents of either 4.2 or 9.0 g/kg DM (the latter only together with C14:0
      supplementation). Various variables of energy, fatty acid and Ca metabolism were
      determined in combined digestibility and respiratory chamber measurements. With
      C14:0 addition the energy loss via the faeces increased (p < 0.05, post hoc test)
      without affecting energy digestibility of the complete diet. The apparent
      digestibility of supplemented C14:0 was higher (p < 0.01) with approximately 0.8
      in the forage-based diet than in the concentrate-based diet (approximately 0.6).
      The elevated levels of plasma C14:0 were mainly accompanied by reduced C18:0 and
      C18:1 levels. The estimated apparent content of metabolizable energy (ME) of
      added C14:0 was either 24.5 MJ/kg (concentrate-based diet) or 32.1 MJ/kg (forage
      based diet). Extra Ca equalized these differences between basal diets and ME
      contents amounted to 33.0 MJ/kg on average. As expected from corresponding slight
      shifts in energy metabolizability, the total efficiency of ME utilization
      increased (p < 0.1) with C14:0. The lower level of dietary Ca was still within
      the range recommended, but adding C14:0 to the concentrate-based diet reduced Ca
      retention in the body of the sheep from 0.9 to -0.1 g/day because of an impaired
      (p < 0.05, post hoc test) net Ca absorption, whereas no effect was found with the
      forage-based diet. With C14:0 addition, plasma total phosphorus (P) and serum
      calcitrol levels increased (p < 0.05, post hoc test) while Ca concentrations did
      not clearly reflect the reduced net Ca absorption. Increasing the dietary Ca
      content prevented adverse effects on Ca retention in the concentrate-based diet
      and improved Ca retention in the forage-based diet. In conclusion, the C14:0
      supplementation reduced Ca availability in concentrate-based diets while an
      additional supply of Ca improved Ca and energy retention. Consequently, Ca supply
      should exceed recommended levels in diet types where dietary lipids are likely to
      reduce Ca availability and a compromise in basal diet type has to found to be
      able to profit best from the energetic value and the methane-suppressing
      properties of C14:0.

PMID- 15972080
TI  - Threonine and tryptophan ratios fed to nursery pigs*.
AB  - The optimal ratio of tryptophan (Trp):lysine (Lys) relative to the ratio of
      threonine (Thr):Lys was studied in 288 crossbred (Cambrough 15 x Canabrid)
      nursery pigs from 7.1 to 15.6 kg BW. Treatments were arranged in a 3 x 3
      factorial with three calculated ratios of true digestible Thr:Lys (0.55, 0.60, or
      0.65) in combination with three Trp:Lys ratios (0.145, 0.170, or 0.195).
      Treatments were replicated with eight pens of four pigs each. The experiment
      lasted 28 day with Phase II (222.6 g CP and 11.9 g true digestible Lys/kg diet,
      initially 24 day of age and 7.1 kg BW) and Phase III (196.2 g CP and 10.1 kg true
      digestible Lys/kg diet, initially 38 day of age and 9.8 kg BW) diets each fed for
      14 day. Threonine by Trp interactions were observed for average daily gain during
      each period, and for daily feed intake during Phase III and overall. Generally,
      Trp addition linearly increased gain and feed intake at a Thr:Lys ratio of 0.60
      and 0.65 but not at a Thr:Lys ratio of 0.55. Gain:feed was increased linearly
      with increasing levels of Trp during both periods. There were no main effects of
      Thr in either time period or overall. Overall, optimal performance was obtained
      in pigs fed the true digestible Trp:Lys ratio of 0.195 at Thr:Lys ratios 0.60 or
      0.65. These results indicate that Trp:Lys ratios above 0.195 may be needed to
      maximize performance in diets containing wheat and barley.

PMID- 15972082
TI  - The birth of an ethics charter for pain medicine.

PMID- 15972083
TI  - Ethics charter from American Academy of Pain Medicine.

PMID- 15972084
TI  - Pressure-controlled lumbar discography in volunteers without low back symptoms.
AB  - BACKGROUND: For lack of a criterion standard for lumbar discogenic pain, the
      validity of lumbar discography cannot be determined directly. The false-positive
      rate of discography, however, can be inferred from the prevalence of positive
      responses in asymptomatic volunteers. Responses in normal volunteers have been
      reported in only three studies, and the prevalence of positive responses has been
      "occasionally, zero, and 10%." None of these studies, however, controlled for
      both pressure of injection and intensity of response. PURPOSE: To determine the
      prevalence of positive responses to lumbar discography in asymptomatic
      volunteers, controlled for pressure of injection and intensity of response. STUDY
      DESIGN/SETTING: Prospective, observational study, conducted in a private spine
      center. Patient Sample. Four lay persons and nine physicians underwent lumbar
      discography, with manometry. OUTCOME MEASURES: The prevalence of painful
      responses were tabulated in terms of the intensity of response, the pressure of
      injection, the segment stimulated, disc morphology, and past history of low back
      pain. RESULTS: Some 56% of discs were not painful, despite maximum
      pressurization. The remaining 44% of discs were painful, to various degrees, at
      various pressures. Most discs required high pressures of injection to be painful
      but even so, were only mildly painful. A receiver-operator curve was derived to
      demonstrate combinations of pain intensity and pressure below which the
      probability of a response was zero or less than 10%. CONCLUSIONS: Lumbar discs in
      asymptomatic volunteers can be made painful, but as a rule, the pain is mild and
      requires high pressures of injection. If attention is paid to pressure of
      injection and intensity of response, operational criteria can be defined that
      provide lumbar discography with a potential false-positive rate of zero or less
      than 10%.

PMID- 15972086
TI  - Zonisamide in the treatment of painful diabetic neuropathy: a randomized, double
      blind, placebo-controlled pilot study.
AB  - BACKGROUND: Painful diabetic neuropathy is a form of neuropathic pain frequently
      encountered as a complication of diabetes mellitus types I and II.
      Pharmacotherapy is one modality of treatment for this distressing and often
      disabling condition, but there is no medication available that consistently
      provides adequate pain relief with acceptable safety and tolerability. Tricyclic
      antidepressants, certain antiepileptic drugs, and opioids have been shown in
      randomized, controlled trials to be of benefit in painful diabetic neuropathy,
      although none has Food and Drug Administration (FDA)-approved labeling for this
      indication. STUDY OBJECTIVE: To analyze the safety and efficacy of zonisamide in
      the treatment of painful diabetic neuropathy. This pilot study is the first
      randomized, controlled trial of zonisamide for the treatment of any neuropathic
      pain disorder. STUDY DESIGN: Forty-two patients 18-80 years of age with type I or
      type II diabetes mellitus and at least a 3-month history of painful diabetic
      neuropathy were screened in the study, and 25 were randomized to zonisamide (N =
      13) or placebo (N = 12). The study drug was titrated over a 6-week period and
      continued at a fixed dosage for a 6-week maintenance period. The mean dosage of
      zonisamide for the maintenance phase was 540 mg/day. OUTCOME MEASURES: Patients
      kept a daily log of their pain using both a 0-100 mm visual analog scale and a 0
      10 Likert scale. RESULT: Pain scores on both the visual analog scale and the
      Likert scale decreased more for the zonisamide group compared with the placebo
      group, regardless of whether the comparison was made for the intent-to-treat
      population, the population that entered the maintenance phase, or the completer
      population, but these differences did not reach statistical significance.
      Tolerability of zonisamide was only fair in this study, which had a high number
      of dropouts from the zonisamide group. CONCLUSION: A larger randomized,
      controlled trial is needed to establish the efficacy and tolerability of
      zonisamide for painful diabetic neuropathy.

PMID- 15972087
TI  - Ethnic differences in pain among outpatients with terminal and end-stage chronic
      illness.
AB  - OBJECTIVE: To explore ethnic and country of origin differences in pain among
      outpatients with terminal and end-stage chronic illness. DESIGN: Cohort study
      within a year-long trial of a palliative care consultation. SETTING: Outpatient
      general medicine practice in an academic medical center. PATIENTS: Ninety
      patients with advanced congestive heart failure, chronic obstructive pulmonary
      disease, or cancer, and with a prognosis between 1 and 5 years. OUTCOME MEASURES:
      Patients' report of pain using the Brief Pain Inventory and analgesic medications
      prescribed by primary care physicians. Differences in pain report and treatment
      were assessed at study entry, at 6 and 12 months. RESULTS: The overall burden of
      pain was high. Patients of color reported more pain than white patients,
      including measures of least pain (P = 0.02), average pain (P = 0.05), and current
      pain (P = 0.03). No significant ethnic group differences in pain were found
      comparing Asian, black, and Latino patients. Although nearly all patients who
      were offered opioid analgesics reported using them, opioids were rarely
      prescribed to any patient. There were no differences in pain between patients
      born in the U.S. and immigrants. CONCLUSIONS: Pain is common among outpatients
      with both terminal and end-stage chronic illness. There do not appear to be any
      differences in pain with regard to country of origin, but patients of color
      report more pain than white patients. Patients of all ethnicities are
      inadequately treated for their pain, and further study is warranted to explore
      the relative patient and physician contributions to the finding of unequal
      symptom burden and inadequate treatment effort.

PMID- 15972088
TI  - Disparities between black and white patients with cancer pain: the effect of
      perception of control over pain.
AB  - CONTEXT: Pain continues to be a problem in ambulatory patients with cancer.
      Disparities in minority patients with pain have been previously identified.
      OBJECTIVE: To examine the effect of perception of control over pain on
      disparities in pain, symptom distress, and functional status in white and black
      patients with cancer. DESIGN: Cross-sectional, descriptive. SETTING: Outpatient
      clinic in a large urban cancer center. PATIENTS: A total of 281 patients who
      reported having pain within the last month and were receiving treatment in the
      cancer center. OUTCOME MEASURES: Pain intensity, pain-related distress,
      functional status, perception of control over pain. RESULTS: Black patients had
      significantly higher pain intensity, more pain-related distress, and reported
      more pain-related interference with function than white patients. Disparities in
      pain-related distress and functional status were significantly reduced and only
      disparities in pain intensity remained when perception of control over pain was
      held constant. CONCLUSIONS: Perception of control over pain is an important
      factor in understanding responses to pain. Increasing a patient's perception of
      control over pain may decrease disparities and increase functional status.

PMID- 15972089
TI  - Alexithymia and pain in three chronic pain samples: comparing Caucasians and
      African Americans.
AB  - OBJECTIVE: African Americans often report greater pain than do Caucasians, but
      the factors responsible for this discrepancy are not known. We examined whether
      alexithymia-the trait of difficulty identifying and describing one's feelings and
      lacking introspection-may contribute to this ethnic group difference. We tested
      whether the mean level of alexithymia is higher, and whether alexithymia and pain
      are more highly correlated, among African Americans than among Caucasians in
      patients with chronic pain disorders. DESIGN: Three cross-sectional,
      correlational studies were conducted on three separate samples of patients with
      chronic pain. Analyses examined the full sample and then Caucasians and African
      Americans separately. SETTING AND PATIENTS: Patients were recruited primarily
      from treatment settings. Samples were patients with rheumatoid arthritis (N =
      155), migraine headaches (N = 160), or systemic lupus erythematosus (N = 123),
      and each sample included only Caucasians or African Americans. MEASURES: The
      Toronto Alexithymia Scale-20 assessed global alexithymia and three alexithymia
      facets. Pain severity, functional disability, or symptoms were also measured on
      each sample. RESULTS: Similar findings occurred across all three samples. African
      Americans had only slightly higher mean alexithymia levels than did Caucasians,
      and this was partly accounted for by socioeconomic differences between groups.
      More importantly, alexithymia correlated only weakly with pain or symptom
      severity for each full sample, but the two ethnic groups showed different
      patterns. Alexithymia correlated positively with pain severity among African
      Americans, but was uncorrelated with pain among Caucasians, even after covarying
      for various socioeconomic variables. CONCLUSIONS: Alexithymia is more correlated
      with pain severity among African Americans with chronic pain disorders than among
      Caucasians, potentially contributing to the higher pain reports among African
      Americans.

PMID- 15972090
TI  - Retrospective analysis of Kadian (morphine sulfate sustained-release capsules) in
      patients with chronic, nonmalignant pain.
AB  - The long-term use of sustained-release morphine for chronic pain was examined by
      reviewing charts from 68 patients taking Kadian (morphine sulfate sustained
      release capsules; Alpharma U.S. Human Pharmaceuticals Branded Products Division,
      Piscataway, NJ) from 1998 to 2003 (mean treatment period 12 months). Patients had
      a wide range of pain conditions, including lower back pain with
      radiculoneuropathy, neck pain, headache, degenerative disc disease, failed back
      syndrome, and radiculoneuropathies. Median daily dose was 60 mg (mean 82.1 mg,
      range 20-400 mg). Dosing frequency was in accordance with prescribing information
      for 97.1% of patients; over half of these patients were maintained on a once
      daily dose. Mean pain scores (visual numeric scale of 0-10) at the end of the
      observation period were reduced from a baseline mean of 7.7-4.9. Kadian use did
      not result in escalation of dose strength or frequency, and was safe and
      efficacious regardless of patient age.

PMID- 15972091
TI  - Successful treatment of phantom radiculopathy with fluoroscopic epidural steroid
      injections.
AB  - Phantom limb pain has been well described in the literature. However, new-onset
      lumbar radicular pain superimposed on baseline lower extremity phantom pain is a
      clinical scenario that can be challenging to recognize. Furthermore, literature
      on recognition and treatment of phantom radiculopathy is all but lacking. We
      present a patient who experienced new-onset lumbar radiculopathy superimposed on
      her phantom pain that was successfully treated with fluoroscopic interlaminar and
      transforaminal epidural steroid injections.

PMID- 15972092
TI  - Leveling the playing field: does pain disparity literature suffer from a
      reporting bias?

PMID- 15972094
TI  - Letter biases in reporting research results relevant to racial and ethnic
      disparities.

PMID- 15972095
TI  - Determinants of racial/ethnic differences in blood pressure management among
      hypertensive patients.
AB  - BACKGROUND: Prior literature has shown that racial/ethnic minorities with
      hypertension may receive less aggressive treatment for their high blood pressure.
      However, to date there are few data available regarding the confounders of
      racial/ethnic disparities in the intensity of hypertension treatment. METHODS: We
      reviewed the medical records of 1,205 patients who had a minimum of two
      hypertension-related outpatient visits to 12 general internal medicine clinics
      during 7/1/01-6/30/02. Using logistic regression, we determined the odds of
      having therapy intensified by patient race/ethnicity after adjustment for
      clinical characteristics. RESULTS: Blacks (81.9%) and Whites (80.3%) were more
      likely than Latinos (71.5%) to have therapy intensified (P = 0.03). After
      adjustment for racial differences in the number of outpatient visits and presence
      of diabetes, there were no racial differences in rates of intensification.
      CONCLUSION: We found that racial/ethnic differences in therapy intensification
      were largely accounted for by differences in frequency of clinic visits and in
      the prevalence of diabetes. Given the higher rates of diabetes and hypertension
      related mortality among Hispanics in the U.S., future interventions to reduce
      disparities in cardiovascular outcomes should increase physician awareness of the
      need to intensify drug therapy more agressively in patients without waiting for
      multiple clinic visits, and should remind providers to treat hypertension more
      aggressively among diabetic patients.

PMID- 15972096
TI  - Thresholds for perception of direction of linear acceleration as a possible
      evaluation of the otolith function.
AB  - BACKGROUND: Previous attempts to measure otolith function using ocular counter
      rolling have shown poor sensitivity and specificity, thereby hindering a useful
      clinical application. We have conducted a study to investigate whether thresholds
      for the perception of the direction of linear acceleration might be an
      alternative for the clinical evaluation of otolith or statolith function.
      METHODS: Perception of the direction of motion was evaluated in 28 healthy
      subjects while all external auditory and visual cues were eliminated. Whole body
      motion stimulus was generated by a motor driven linear sled at a stimulus
      frequency of 1 Hz at a linear acceleration ranging from 0 to maximum 40 cm/s2.
      Subjects were required to correctly indicate the direction of motion (anterior
      posterior or lateral) or whether they were stationary. Both velocity and
      acceleration thresholds were measured. RESULTS: The median acceleration
      thresholds for the perception of direction of linear movement for anterior
      posterior movement was 8.5 cm/s2 and for lateral movement 6.5 cm/s2. According to
      the literature, acceleration thresholds depend on the stimulus profile whereas
      velocity thresholds do not. The median velocity thresholds for the perception of
      direction of linear movement for anterior-posterior movement was 13.5 cm/s and
      for lateral movement was 10.4 cm/s. The median velocity thresholds for the
      perception of direction of linear movement for anterior-posterior movement
      increased linearly with age, whereas the median velocity threshold for lateral
      movement was not correlated with age. CONCLUSION: The thresholds found in this
      study are lower than reported in the literature before which may be due to the
      repetitive predictive sinusoidal stimulus which makes it relatively easy to lower
      the threshold by learning already within one test profile. The variability is
      large in line with the previous literature, but our experiments indicate that
      variability decreases after a training session. We interpret the literature and
      our current results that linear velocity thresholds after some training might
      reflect the sensitivity of the otolith system per se.

PMID- 15972097
TI  - Contextual weighting for Support Vector Machines in literature mining: an
      application to gene versus protein name disambiguation.
AB  - BACKGROUND: The ability to distinguish between genes and proteins is essential
      for understanding biological text. Support Vector Machines (SVMs) have been
      proven to be very efficient in general data mining tasks. We explore their
      capability for the gene versus protein name disambiguation task. RESULTS: We
      incorporated into the conventional SVM a weighting scheme based on distances of
      context words from the word to be disambiguated. This weighting scheme increased
      the performance of SVMs by five percentage points giving performance better than
      85% as measured by the area under ROC curve and outperformed the Weighted
      Additive Classifier, which also incorporates the weighting, and the Naive Bayes
      classifier. CONCLUSION: We show that the performance of SVMs can be improved by
      the proposed weighting scheme. Furthermore, our results suggest that in this
      study the increase of the classification performance due to the weighting is
      greater than that obtained by selecting the underlying classifier or the kernel
      part of the SVM.

PMID- 15972098
TI  - In vivo effect of interleukin-1beta and interleukin-1RA on oocyte cytoplasmic
      maturation, ovulation, and early embryonic development in the mare.
AB  - A growing body of evidence suggests that the interleukin-1 system is involved in
      periovulatory events. Previous work from our lab demonstrated that in the mare,
      interleukin-1beta (IL-1beta) increases the ovulatory rate of metaphase II
      oocytes. The present study was conducted to analyze in vivo the effect of IL-1 on
      oocyte cytoplasmic maturation, ovulation and pregnancy rate. In the present work,
      IL-1beta (experiment 1, n = 13; experiment 2, n = 25) and interleukin-1RA (IL
      1RA; experiment 1, n = 25) were injected intrafollicularly by using the
      transvaginal ultrasound-guided injection method. Injections were performed on
      cyclic mares when the diameter of the growing dominant follicle reached 30-34 mm.
      In experiment 1, mares were inseminated the day of the treatment and all the
      other day until ovulation. The time of ovulation was determined and a pregnancy
      diagnosis was performed 14 days after ovulation of the injected follicle. In
      experiment 2, the cumulus-oocyte complex from each injected follicle was
      collected by transvaginal ultrasound-guided aspiration 38 h after the
      intrafollicular injection. Oocyte nuclear stage and oocyte cytoplasmic maturation
      were assessed by analyzing chromatin configuration, cortical granules migration
      and mitochondria distribution under a confocal microscope. The results from
      experiment 1 confirm that an intrafollicular injection of 1 microgram IL-1beta
      induces ovulation in the mare whereas IL-1RA has no effect at the dose used in
      the present study. Furthemore, we demonstrated, that in our experimental
      conditions, IL-1beta and IL-1RA induced a decrease in embryo development.
      Experiment 2 leads us to observe that IL-1beta is unable to induce cortical
      granules migration and remodelling of mitochondria, that commonly occurs during
      oocyte maturation, whereas it acts on nuclear maturation. This result may explain
      the decrease in embryo development we observed after IL-1beta intrafollicular
      injection. In conclusion, the present study tends to demonstrate that IL-1beta
      plays a role in the ovulatory process and may acts on oocyte maturation in the
      mare, but additional factors are required to complete equine oocyte cytoplasmic
      maturation to allow embryo development.

PMID- 15972099
TI  - The morbidity and mortality following a diagnosis of peripheral arterial disease:
      long-term follow-up of a large database.
AB  - BACKGROUND: Awareness of the significance of peripheral arterial disease is
      increasing, but quantitative estimates of the ensuing burden and the impact of
      other risk factors remains limited. The objective of this study was to fill this
      need. METHODS: Morbidity and mortality were examined in 16,440 index patients
      diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985
      and 1995. Medical history and patient characteristics were available
      retrospectively to January 1980 and follow-up was complete to March 1998. Crude
      and adjusted event rates were calculated and Kaplan-Meier survival curves
      estimated. Cox proportional hazards analyses were conducted to examine the effect
      of risk factors on these rates. Patients suffering a myocardial infarction or
      ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half
      of the index patients were male; the majority was over age 65; 73% had at least
      one additional risk factor at index diagnosis; 10% suffered a subsequent stroke,
      another 10% a myocardial infarction, and 49% died within the mean follow-up of
      5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after
      a myocardial infarction (6.3%) but slightly lower than that in patients suffering
      a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at
      highest risk of death and other events. CONCLUSION: A diagnosis of peripheral
      arterial disease is critical evidence of more widespread atherothrombotic
      disease, with substantial risks of subsequent cardiovascular events and death.
      Given that the majority has additional comorbidities, these risks are further
      increased.

PMID- 15972100
TI  - Well-being in residency training: a survey examining resident physician
      satisfaction both within and outside of residency training and mental health in
      Alberta.
AB  - BACKGROUND: Despite the critical importance of well-being during residency
      training, only a few Canadian studies have examined stress in residency and none
      have examined well-being resources. No recent studies have reported any
      significant concerns with respect to perceived stress levels in residency. We
      investigated the level of perceived stress, mental health and understanding and
      need for well-being resources among resident physicians in training programs in
      Alberta, Canada. METHODS: A mail questionnaire was distributed to the entire
      resident membership of PARA during 2003 academic year. PARA represents each of
      the two medical schools in the province of Alberta. RESULTS: In total 415 (51 %)
      residents participated in the study. Thirty-four percent of residents who
      responded to the survey reported their life as being stressful. Females reported
      stress more frequently than males (40% vs. 27%, p < 0.02). Time pressure was
      reported as the number one factor contributing to stress (44% of males and 57% of
      females). A considerable proportion of residents would change their specialty
      program (14%) and even more would not pursue medicine (22%) if given the
      opportunity to relive their career. Up to 55% of residents reported experiencing
      intimidation and harassment. Intimidation and harassment was strongly related to
      gender (12% of males and 38% of females). Many residents (17%) rated their mental
      health as fair or poor. This was more than double the amount reported in the
      Canadian Community Health Survey from the province (8%) or the country (7%).
      Residents highly valued their colleagues (67%), program directors (60%) and
      external psychiatrist/psychologist (49%) as well-being resources. Over one third
      of residents wished to have a career counselor (39%) and financial counselor
      (38%). CONCLUSION: Many Albertan residents experience significant stressors and
      emotional and mental health problems. Some of which differ among genders. This
      study can serve as a basis for future resource application, research and advocacy
      for overall improvements to well-being during residency training.

PMID- 15972101
TI  - Secondary prevention of allergic symptoms in a dairy farmer by use of a milking
      robot.
AB  - BACKGROUND: Animal-derived allergens include lipocalins which play an increasing
      role in occupational respiratory sensitizations. The prevention of sensitization
      in stock farming is often difficult due to intense exposure, with traditional
      milking still requiring close animal contact. Complete avoidance of allergen
      exposure is only possible if stock farming is abandoned. This is, however, often
      not feasible in small dairy plants because of the resulting loss of income. CASE
      PRESENTATION: In a 37-year-old female farmer daily asthmatic complaints appeared,
      associated with cow dust-derived allergen exposure by milking with a conventional
      device. Respiratory symptoms increased during a period of 12 years. Allergic
      bronchial asthma was diagnosed, caused by sensitization against cow dust-derived
      allergens, as demonstrated by positive skin prick test and by detection of IgE
      antibodies. In a separate specific inhalation challenge test using a 10% extract
      of cow dust-derived allergens a 330% increase of airway resistance was detected.
      To enable further dairy farming, a milking robot was installed in 1999, i.e., an
      automatic milking system. The novel milking technique reduced the daily exposure
      from over 2 hours to approximately 10 min. The clinical course after the
      installation of the milking robot was favourable, with less frequent allergic and
      asthmatic symptoms. Furthermore, asthma medication could be reduced. Improvement
      was noted also in terms of lung-function and decreased total serum IgE.
      CONCLUSION: The case presented and the evidence from the literature indicates
      that the strategy of exposure minimization to allergens at workplaces can be an
      effective alternative to total elimination. In farmers with cow dust allergy a
      milking robot is an appropriate technical measure to minimize allergen-exposure.

PMID- 15972102
TI  - Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung
      injury.
AB  - BACKGROUND: Alveolar macrophages play an important role during the development of
      acute inflammatory lung injury. In the present study, in vivo alveolar macrophage
      depletion was performed by intratracheal application of dichloromethylene
      diphosphonate-liposomes in order to study the role of these effector cells in the
      early endotoxin-induced lung injury. METHODS: Lipopolysaccharide was applied
      intratracheally and the inflammatory reaction was assessed 4 hours later.
      Neutrophil accumulation and expression of inflammatory mediators were determined.
      To further analyze in vivo observations, in vitro experiments with alveolar
      epithelial cells and alveolar macrophages were performed. RESULTS: A 320%
      increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was
      observed in macrophage-depleted compared to macrophage-competent
      lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the
      interstitial space. Monocyte chemoattractant protein-1 concentration in
      bronchoalveolar lavage fluid was significantly increased in the absence of
      alveolar macrophages. This phenomenon was underlined by in vitro experiments with
      alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte
      chemoattractant protein-1 in the airways diminished neutrophil accumulation.
      CONCLUSION: These data suggest that alveolar macrophages play an important role
      in early endotoxin-induced lung injury. They prevent neutrophil influx by
      controlling monocyte chemoattractant protein-1 production through alveolar
      epithelial cells. Alveolar macrophages might therefore possess robust anti
      inflammatory effects.

PMID- 15972103
TI  - Peripheral arterial disease: a high risk - but neglected - disease population.
AB  - Peripheral arterial disease (PAD) is a common, progressive manifestation of
      atherothrombotic vascular disease, which should be managed no different to
      cardiac disease. Indeed, there is growing evidence that PAD patients are a high
      risk group, although still relatively under-detected and under treated. This is
      despite the fact that PAD patients are an increased mortality rate comparable to
      those with pre-existing or established cardiovascular disease [myocardial
      infarction, stroke]. With a holistic approach to atherothrombotic vascular
      disease, our management of PAD can only get better.

PMID- 15972104
TI  - Are chronic low back pain outcomes improved with co-management of concurrent
      depression?
AB  - OBJECTIVE: To discuss the role of depression in chronic lower back pain and
      comment on appropriate methods of screening and co-management. DATA SOURCES: The
      current scientific literature was investigated using the online web databases
      CINAHL, Medline/PUBMED, Proquest, Meditext and from manual library searches. DATA
      EXTRACTION: Databases were searched from 1980 to the present (2005). Articles
      were searched with the key words "depression" and "low back pain". Over three
      hundred articles were sourced and articles were then selected on their relevance
      to the chronic spinal pain states that present to manual therapy practitioners.
      DATA SYNTHESIS: Pain is a subjective awareness of peripheral nociceptive
      stimulation, projected from the thalamus to the cerebral cortex with each
      individual's pain experience being mediated by his or her psychological state.
      Thus a psychological component will often be associated with any painful
      experience. A number of studies suggest (among other things) that the incidence
      of depression predicts chronicity in lower back pain syndromes but that chronic
      lower back pain does not have the reciprocal action to predict depression.
      CONCLUSION: The aetiology of chronic pain is multifactorial. There is sufficient
      evidence in the literature to demonstrate a requirement to draw treatment options
      from many sources in order to achieve a favourable pain relief outcome. The
      treatment should be multimodal, including mental and emotional support,
      counseling and herbal advice. While a strong correlation between depression and
      chronic low back pain can be demonstrated, an apparent paucity of literature that
      specifically addresses the patient response to chiropractic treatment and
      concurrent psychotherapy identifies the need for prospective studies of this
      nature to be undertaken. It is likely that multimodal/multidisciplinary treatment
      approaches should be encouraged to deal with these chronic lower back pain
      syndromes.

PMID- 15972105
TI  - FGF10/FGFR2b signaling plays essential roles during in vivo embryonic
      submandibular salivary gland morphogenesis.
AB  - BACKGROUND: Analyses of Fgf10 and Fgfr2b mutant mice, as well as human studies,
      suggest that FGF10/FGFR2b signaling may play an essential, nonredundant role
      during embryonic SMG development. To address this question, we have analyzed the
      SMG phenotype in Fgf10 and Fgfr2b heterozygous and null mutant mice. In addition,
      although previous studies suggest that the FGF10/FGFR2b and FGF8/FGFR2c signaling
      pathways are functionally interrelated, little is known about the functional
      relationship between these two pathways during SMG development. We have designed
      in vivo and in vitro experiments to address this question. RESULTS: We analyzed
      Fgf10 and Fgfr2b heterozygous mutant and null mice and demonstrate dose-dependent
      SMG phenotypic differences. Hypoplastic SMGs are seen in Fgf10 and Fgfr2b
      heterozygotes whereas SMG aplasia is seen in Fgf10 and Fgfr2b null embryos.
      Complementary in vitro studies further indicate that FGF10/FGFR2b signaling
      regulates SMG epithelial branching and cell proliferation. To delineate the
      functional relationship between the FGF10/FGFR2b and FGF8/FGFR2c pathways, we
      compared the SMG phenotype in Fgfr2c+/Delta/Fgf10+/- double heterozygous mice to
      that seen in wildtype, Fgf10+/- (Fgfr2c+/+/Fgf10+/-) and Fgfr2c+/Delta
      (Fgfr2c+/Delta/Fgf10+/+) single heterozygous mutant littermates and demonstrate
      genotype-specific SMG phenotypes. In addition, exogenous FGF8 was able to rescue
      the abnormal SMG phenotype associated with abrogated FGFR2b signaling in vitro
      and restore branching to normal levels. CONCLUSION: Our data indicates that
      FGF10/FGFR2b signaling is essential for the SMG epithelial branching and
      histodifferentiation, but not earliest initial bud formation. The functional
      presence of other endogenous signaling pathways could not prevent complete death
      of embryonic SMG cells in Fgf10 and Fgfr2b null mice. Though we were able to
      rescue the abnormal phenotype associated with reduced in vitro FGF10/FGFR2b
      signaling with exogenous FGF8 supplementation, our results indicate that the
      FGF10/FGFR2b and FGF8/FGFR2c are nonredundant signaling pathways essential for in
      vivo embryonic SMG development. What remains to be determined is the in vivo
      functional relationship between the FGF10/FGFR2b signal transduction pathway and
      other key signaling pathways, and how these pathways are integrated during
      embryonic SMG development to compose the functional epigenome.

PMID- 15972106
TI  - The combination of intravitreal triamcinolone and phacoemulsification surgery in
      patients with diabeticfoveal oedema and cataract.
AB  - BACKGROUND: The management of diabetic patients with refractory macular oedema or
      patients with no adequate pre-operative view to administer laser treatment
      provide a challenge to the ophthalmologist. We wished to assess the use, safety
      and effect of intravitreal triamcinolone injection at the time of cataract
      surgery in patients with diabetic foveal oedema and sight limiting lens
      opacities. METHOD: This was a longitudinal non-randomised prospective pilot study
      in 18 eyes (12 patients). All patients had visually significant lens opacities
      and either persistent diabetic foveal oedema unresponsive to laser treatment
      group A, or foveal oedema with no adequate pre-operative view for laser treatment
      group B. The cataract surgery was carried out under full aseptic technique using
      a self-sealing temporal incision and a foldable acrylic lens. Intravitreal
      triamcinolone was given infratemporally pars plana at the completion of the
      cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months and then
      every 3 months as required. The Wilcoxin matched-pairs test was used to assess
      the significance of the improvement in visual acuity at 2 months. RESULTS: Twelve
      patients with a total of 18 eyes were included in the study. There were 10
      patients (15 eyes) in group A and 3 patients (3 eyes) in group B. Preoperatively
      16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of
      patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at
      two months review ranged from 6/6 to CF with 9 eyes (50%) achieving 6/12 or
      better (7 eyes (47%) in group A and 2 eyes (67%) in group B). Three eyes had no
      recorded improvement in visual acuity, but no eyes had deterioration in acuity.
      The improvement in visual acuity was significant at p = 0.001. There were no
      significant sight threatening complications. CONCLUSION: Intravitreal
      triamcinolone has been shown to lead to an improvement in macular oedema and
      visual improvement in diabetic patients not undergoing cataract surgery but has
      not, to our knowledge, been previously used in a study like this one.We suggest
      that intravitreal injection at the time of cataract surgery could be carried out
      safely with encouraging visual outcomes in patients with diabetic foveal oedema
      and cataract.

PMID- 15972107
TI  - MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale
      characterisation.
AB  - BACKGROUND: The picture of dog mtDNA diversity, as obtained from geographically
      wide samplings but from a small number of individuals per region or breed, has
      revealed weak geographic correlation and high degree of haplotype sharing between
      very distant breeds. We aimed at a more detailed picture through extensive
      sampling (n = 143) of four Portuguese autochthonous breeds - Castro Laboreiro
      Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and
      comparatively reanalysing published worldwide data. RESULTS: Fifteen haplotypes
      belonging to four major haplogroups were found in these breeds, of which five are
      newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A
      haplotype, while all other breeds contained a diverse pool of existing lineages.
      The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese
      breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog
      shared no haplotypes with the other Portuguese breeds.A review of mtDNA
      haplotypes in dogs across the world revealed that: (a) breeds tend to display
      haplotypes belonging to different haplogroups; (b) haplogroup A is present in all
      breeds, and even uncommon haplogroups are highly dispersed among breeds and
      continental areas; (c) haplotype sharing between breeds of the same region is
      lower than between breeds of different regions and (d) genetic distances between
      breeds do not correlate with geography. CONCLUSION: MtDNA haplotype sharing
      occurred between Serra da Estrela Mountain dogs (with putative origin in the
      centre of Portugal) and two breeds in the north and south of the country-with the
      Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the
      Serra da Estrela Mountain Dog) and the southern Portuguese Sheepdog. In contrast,
      the Azores Cattle Dog did not share any haplotypes with the other Portuguese
      breeds, but with dogs sampled in Northern Europe. This suggested that the Azores
      Cattle Dog descended maternally from Northern European dogs rather than
      Portuguese mainland dogs. A review of published mtDNA haplotypes identified
      thirteen non-Portuguese breeds with sufficient data for comparison. Comparisons
      between these thirteen breeds, and the four Portuguese breeds, demonstrated
      widespread haplotype sharing, with the greatest diversity among Asian dogs, in
      accordance with the central role of Asia in canine domestication.

PMID- 15972108
TI  - Serum biomarkers in acute respiratory distress syndrome an ailing prognosticator.
AB  - The use of biomarkers in medicine lies in their ability to detect disease and
      support diagnostic and therapeutic decisions. New research and novel
      understanding of the molecular basis of the disease reveals an abundance of
      exciting new biomarkers who present a promise for use in the everyday clinical
      practice. The past fifteen years have seen the emergence of numerous clinical
      applications of several new molecules as biologic markers in the research field
      relevant to acute respiratory distress syndrome (translational research). The
      scope of this review is to summarize the current state of knowledge about serum
      biomarkers in acute lung injury and acute respiratory distress syndrome and their
      potential value as prognostic tools and present some of the future perspectives
      and challenges.

PMID- 15972110
TI  - Patient positioning and ventilator-associated pneumonia.
AB  - Rotational beds, prone position, and semi-recumbent position have been proposed
      as procedures to prevent ventilator-associated pneumonia (VAP). Rotational
      therapy uses a special bed designed to turn continuously, or nearly continuously,
      the patient from side to side; specific designs include kinetic therapy and
      continuous lateral rotation therapy. A meta-analysis of studies evaluating the
      effect of rotational bed therapy shows a decrease in the risk of pneumonia but no
      effect on mortality. Two studies reported a lower risk of VAP in patients placed
      in a prone position, with no effect on mortality. Studies using radiolabeled
      enteral feeding solutions in mechanically ventilated patients have reported that
      aspiration of gastric contents occurs to a greater degree when patients are in
      the supine position, compared with the semirecumbent position. One study reported
      a lower rate of VAP in patients randomized to semi-recumbent compared to supine
      position. Although each of the techniques discussed in this paper has been shown
      to reduce the risk of VAP, none has been shown to affect mortality. The available
      evidence suggests that semi-recumbent position should be used routinely,
      rotational therapy should be considered in selected patients, and prone position
      should not be used as a technique to reduce the risk of VAP.

PMID- 15972109
TI  - U94 alters FN1 and ANGPTL4 gene expression and inhibits tumorigenesis of prostate
      cancer cell line PC3.
AB  - BACKGROUND: Insensitivity of advanced-stage prostate cancer to androgen ablation
      therapy is a serious problem in clinical practice because it is associated with
      aggressive progression and poor prognosis. Targeted therapeutic drug discovery
      efforts are thwarted by lack of adequate knowledge of gene(s) associated with
      prostate tumorigenesis. Therefore there is the need for studies to provide leads
      to targeted intervention measures. Here we propose that stable expression of U94,
      a tumor suppressor gene encoded by human herpesvirus 6A (HHV-6A), could alter
      gene expression and thereby inhibit the tumorigenicity of PC3 cell line.
      Microarray gene expression profiling on U94 recombinant PC3 cell line could
      reveal genes that would elucidate prostate cancer biology, and hopefully identify
      potential therapeutic targets. RESULTS: We have shown that stable expression of
      U94 gene in PC3 cell line inhibited its focus formation in culture, and
      tumorigenesis in nude mice. Moreover gene expression profiling revealed dramatic
      upregulation of FN 1 (fibronectin, 91 +/- 16-fold), and profound downregulation
      of ANGPTL 4 (angiopoietin-like-4, 20 +/- 4-fold) in U94 recombinant PC3 cell
      line. Quantitative real-time polymerase chain reaction (QRT-PCR) analysis showed
      that the pattern of expression of FN 1 and ANGPTL 4 mRNA were consistent with the
      microarray data. Based on previous reports, the findings in this study implicate
      upregulation of FN 1 and downregulation of ANGPTL 4 in the anti tumor activity of
      U94. Genes with cancer inhibitory activities that were also upregulated include
      SERPINE 2 (serine/cysteine protease inhibitor 2, 7 +/- 1-fold increase) and
      ADAMTS 1 (a disintegrin-like and metalloprotease with thrombospondin type 1
      motif, 7 +/- 2-fold increase). Additionally, SPUVE 23 (serine protease 23) that
      is pro-tumorigenic was significantly downregulated (10 +/- 1-fold). CONCLUSION:
      The dramatic upregulation of FN 1 and downregulation of ANGPTL 4 genes in PC3
      cell line stably expressing U94 implicate up-regulation of FN 1 and
      downregulation of ANGPTL 4 in anti tumor activity of U94. Further studies are
      necessary to determine functional roles of differentially expressed genes in U94
      recombinant PC3 cell line, and hopefully provide leads to potential therapeutic
      targets in prostate cancer.

PMID- 15972111
TI  - Ventilator-associated pneumonia: issues related to the artificial airway.
AB  - Pooling of contaminated secretions above the cuff of the endotracheal tube
      predisposes patients to ventilator-associated pneumonia (VAP). Subglottic
      secretion drainage requires a special endotracheal tube that has a separate lumen
      that opens in the subglottic region above the tracheal tube. A recent meta
      analysis of the 5 randomized clinical trials that evaluated the efficacy of
      removing these secretions found that this technique significantly reduces the
      incidence of VAP. One cost-effectiveness analysis showed savings of dollar 4,900
      per episode of VAP prevented. Greatest benefit is derived by patients requiring
      fewer than 10 days of mechanical ventilation and not exposed to antibiotic
      therapy. Maintaining the intracuff pressure between 25 and 30 cm H2O is mandatory
      to guarantee effective drainage and safety. While silver-coated endotracheal
      tubes reduce pseudomonas pneumonia in intubated dogs and delay airway
      colonization in intubated patients, evaluation of studies with a variety of case
      mixes is warranted to identify subsets likely to benefit from the technique
      before it is implemented on a large scale. A patient who has a colonized airway
      and who undergoes percutaneous tracheotomy has an increased risk of VAP,
      particularly due to Pseudomonas aeruginosa, in the week following the procedure.
      As many studies suggest that incidence of VAP is highly dependent on the
      strategies of airway management, health care workers should be alerted to issues
      related to the artificial airway.

PMID- 15972112
TI  - The gastrointestinal tract and ventilator-associated pneumonia.
AB  - The gastrointestinal tract is believed to play an important role in ventilator
      associated pneumonia (VAP), because during critical illness the stomach often is
      colonized with enteric Gram-negative bacteria. These are the same bacteria that
      frequently are isolated from the sputum of patients with VAP. Interventions such
      as selective decontamination of the digestive tract (SDD), use of sucralfate for
      stress ulcer prophylaxis, and enteral feeding strategies that preserve gastric
      pH, or lessen the likelihood of pulmonary aspiration, are used to decrease the
      incidence of VAP. A review of both meta-analyses and large randomized controlled
      trials providing Level I evidence on these topics has led to the following
      conclusions. First, SDD substantially decreases the incidence of VAP and may have
      a modest positive effect on mortality. However, there is strong contravening
      evidence that SDD promotes infections by Gram-positive bacteria. In the context
      of an emerging public health crisis from the steady rise in drug-resistant Gram
      positive bacteria, we cannot endorse the general use of SDD to prevent VAP.
      Rather, therapy should be focused on strategies other than antibiotic
      prophylaxis. Second, in patients who are at risk for clinically important
      gastrointestinal bleeding, a histamine-2 receptor antagonist should be used for
      stress ulcer prophylaxis, rather than sucralfate, because histamine-2 receptor
      antagonist provides substantially better protection without substantially
      increasing the risk of VAP. Third, post-pyloric enteral feeding may reduce the
      incidence of VAP.

PMID- 15972113
TI  - Noninvasive positive-pressure ventilation and ventilator-associated pneumonia.
AB  - There is much interest in the use of noninvasive positive-pressure ventilation
      (NPPV) to prevent intubation and afford a survival benefit for patients. The risk
      of pneumonia in patients receiving NPPV has been reported in 12 studies. Compared
      to patients receiving invasive mechanical ventilation (4 studies), the pneumonia
      rate is lower with the use of NPPV (relative risk [RR] 0.15, 95% confidence
      interval [CI] 0.04 to 0.58, p = 0.006). Compared to patients assigned to invasive
      mechanical ventilation (3 studies), in which some of the patients assigned to
      NPPV did not respond and were eventually intubated, there was also a benefit for
      the use of NPPV (RR 0.24, 95% CI 0.08 to 0.73, p = 0.01). In studies in which
      patients assigned to NPPV were compared to patients assigned to standard therapy
      (5 studies), in which some of the patients in each group were eventually
      intubated, there was benefit shown for the use of NPPV (RR 0.56, 95% CI 0.31 to
      1.02, p = 0.06). When this meta-analysis is repeated without the results of the
      negative study for NPPV (extubation failure), there is a stronger benefit in
      support of NPPV to decrease the risk of pneumonia in the remaining 4 studies (RR
      0.38, 95% CI 0.20 to 0.73, p = 0.003). A meta-analysis combining the results from
      the 12 studies reviewed shows a strong benefit for NPPV (RR 0.31, 95% CI 0.16 to
      0.57, p = 0.0002). One randomized controlled trial of continuous positive airway
      pressure compared with standard treatment in patients who developed acute
      hypoxemia after elective major abdominal surgery reported a lower rate of
      pneumonia with continuous positive airway pressure (2% vs 10%, RR 0.19, 95% CI
      0.04 to 0.88, p = 0.02). In patients who are appropriate candidates for NPPV or
      continuous positive airway pressure, the available evidence suggests a benefit in
      terms of a lower risk of pneumonia. Perhaps "endotracheal-tube-associated
      pneumonia" is a better term than "ventilator-associated pneumonia."

PMID- 15972114
TI  - Antimicrobial treatment of ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia is a common complication of ventilatory support
      for patients with acute respiratory failure and is associated with increased
      morbidity, mortality, and costs. Optimal antimicrobial therapy is an essential
      part of successful management of ventilator-associated pneumonia. Numerous safe
      and effective antimicrobial drugs are available, and their efficacy can be
      optimized by attention to basic pharmacokinetic and pharmacodynamic principles.
      An adequate initial empiric antimicrobial regimen is essential, because
      inadequate initial therapy is consistently associated with increased mortality.
      This regimen must be selected before final microbiology results become known, but
      likely pathogens and antimicrobial resistance patterns can be predicted based on
      published guidelines, patient-specific factors, and local epidemiologic data.
      Nevertheless, the initial regimen must often be broad-spectrum and typically
      requires combination therapy, with 2 or 3 different drugs, if there are risk
      factors for multidrug-resistant pathogens. The antimicrobial regimen can be
      narrowed or discontinued as culture and susceptibility results permit. This de
      escalation strategy ensures adequate initial antimicrobial therapy for most
      patients but lessens unnecessary antimicrobial exposure. The best diagnostic
      approach used to guide therapy, the optimum duration of therapy, and the roles of
      combination therapy, rotating therapy, and unconventional approaches to
      antimicrobial therapy all remain uncertain.

PMID- 15972115
TI  - Cost-effectiveness issues in ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia has attracted considerable interest as a subject
      of clinical efficacy assessment research. This article summarizes recommendations
      made by the United States Public Health Service Panel on Cost-Effectiveness in
      Health and Medicine and by a panel convened by the American Thoracic Society to
      address economic analyses in critical care. The following recommendations are
      made for the performance of cost-efficacy studies in ventilator-associated
      pneumonia. For mortality-based studies, only data from prospective and blinded
      randomized trials are suitable for analysis. For cost-minimization studies,
      observational studies may be useful but should use rigorous matching schemes.
      Estimates for the quality of life of patients surviving an episode of ventilator
      associated pneumonia should be based on the disease that required mechanical
      ventilation or compared to data available for survivors of the respiratory
      distress syndrome, whichever diagnosis provides a lessened quality of life.
      Within an individual intensive care unit the greatest cost savings come from
      constructing a cohesive and unified approach to many issues seen in the unit.

PMID- 15972116
TI  - Clinical approach to the patient with suspected ventilator-associated pneumonia.
AB  - Management of ventilator-associated pneumonia needs to balance the avoidance of
      unnecessary antibiotic overuse with the provision of adequate initial empiric
      therapy. A clinical diagnosis based on new pulmonary opacity and purulent
      respiratory secretions plus other signs of inflammation is valuable in screening
      for patients with suspected ventilator-associated pneumonia. A rational strategy
      starts with immediate initiation of adequate antibiotics and collection of
      respiratory secretions to evaluate the causative organism. As a minimum, an
      endotracheal aspirate with direct staining and quantitative cultures should be
      obtained. Overall, the need to choose adequate antibiotics correctly and
      expeditiously calls for the use of broad-spectrum antibiotics, but the choice
      should be narrowed quickly in the light of microbiologic information. However,
      some patients (those who develop an infection within 5 days of hospitalization,
      those without recent antibiotic exposure, and those without hospitalization in
      the past 3 months) are at low risk of infection by resistant organisms. In that
      subset, adequate initial selection could be a non-pseudomonal third-generation
      cephalosporin, since antibiotics should target usual community-acquired organisms
      in addition to some Enterobacteriaceae and Staphylococcus aureus. Coverage of
      methicillin-resistant S. aureus should be limited only to intensive care units
      with concomitant index cases and to patients under antibiotic exposure. Patients
      at risk of Pseudomonas aeruginosa (e.g., 1 week of prior hospitalization or
      chronic obstructive pulmonary disease) require initial use of a combination of
      piperacilin/tazobactam and ciprofloxacin, or amikacin plus imipenem, meropenem,
      or an antipseudomonal cephalosporin. If risk of Acinetobacter baumannii exists,
      one of these agents should be a carbapenem. After 48 hours of therapy, each
      patient should be re-evaluated based mainly on resolution of hypoxemia and fever
      plus the initial microbiologic information. Whereas broad-spectrum therapy is
      initially warranted in many patients, this treatment may be narrowed considerably
      as culture results identify the causative organism and its sensitivity. Recent
      data suggest that reducing overall treatment duration to a maximum of 1 week is
      safe, effective and is less likely to promote the growth of resistant organisms
      in patients who are clinically improving. Optimal management should be based on a
      strategy combining early high doses of an effective agent for a short period of
      time, which is then simplified in the light of microbiologic information.

PMID- 15972117
TI  - Conference summary: ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP), which is usually defined as an infection
      occurring greater than 48 hours after hospital admission in a patient requiring
      mechanical ventilation, is an entity that should be viewed as a subcategory of
      health-care-associated pneumonia, which includes any patient who was hospitalized
      in an acute care hospital for 2 or more days within 90 days of the infection;
      resided in a nursing home or long-term care facility; received recent antibiotic
      therapy, chemotherapy, or wound care within the past 30 days of the current
      infection; or attended a hospital or hemodialysis clinic. VAP is the most
      frequent intensive-care-unit (ICU)-acquired infection among patients receiving
      mechanical ventilation. In contrast to infections of other frequently involved
      organs (eg, urinary tract and skin), for which mortality is low, the mortality
      rate for VAP ranges from 20% to 50% and can reach 70% in some specific settings
      or when lung infection is caused by high-risk pathogens and/or when initial
      antibiotic therapy is inappropriate. Although the attributable mortality rate for
      VAP is still debated, it has been shown that these infections prolong both the
      duration of ventilation and the duration of ICU stay. These prolonged
      hospitalizations underscore the considerable financial burden imposed by the
      development of VAP. The causes of VAP are many and may vary by hospital, patient
      population, and type of ICU, emphasizing the need for timely, local surveillance
      data. In many cases infection is caused by multiple-drug-resistant pathogens.
      Risk factors for such resistant microorganisms are the duration of mechanical
      ventilation, prior antibiotic treatment, and contact with the health care system.
      Preventive measures should be guided with regard to a full understanding of
      pathogenesis and epidemiology. Because respiratory-tract colonization of ICU
      patients is generally very complex, corresponding to a mix of self-colonization
      and cross-transmission, only a multifaceted and multidisciplinary program can be
      effective. Antimicrobial therapy of patients with VAP should follow a 2-stage
      process. The first stage involves administering broad-spectrum antibiotics to
      avoid inappropriate treatment in patients with true bacterial pneumonia. The
      second stage focuses on trying to achieve this objective without over-using and
      abusing antibiotics, combining a number of different steps, such as stopping
      therapy in patients with a low probability of the disease, streamlining treatment
      once the etiologic agent is known, switching to monotherapy after days 3-5, and
      shortening duration of therapy to 7-8 days, as dictated by the patient's clinical
      response to therapy and information about the bacteriology of the infection.

PMID- 15972118
TI  - Support for limited brain availability of tyrosine in patients with
      schizophrenia.
AB  - Several mechanisms have been suggested to account for altered dopaminergic
      neurotransmission in schizophrenia. The brain is the only organ for which amino
      acid transport is limited and competition for transport over the blood-brain
      barrier (BBB) occurs at physiological plasma concentrations. One line of research
      suggests that patients with schizophrenia have altered brain levels of the
      essential amino acid tyrosine, the precursor for the synthesis of dopamine. The
      most common hypothesis is that less tyrosine is available because of competition
      with elevated levels of other amino acids. By consequence, the synthesis of
      dopamine in the brain will decrease. In contrast, another line of evidence
      suggests a change in the affinity for one of the transport proteins. A limitation
      of this research has been that the systems for amino-acid transport across the
      BBB have not been fully characterized at a molecular or functional level. The L
      system is the major system for transport of tyrosine across cell membranes
      including the BBB. The A system is also involved in this transport. Earlier in
      vitro studies using fibroblasts have demonstrated a normal L system in
      schizophrenia but nevertheless reduced tyrosine transport. The combination of
      molecular research, fibroblast techniques, and brain imaging provides a new basis
      for clinical research on the role of amino-acid membrane transport in
      schizophrenia.

PMID- 15972119
TI  - [Adult stem cells and possible mechanisms of its differentiation--editorial].
AB  - Adult stem cells are the multi-potential cells, which exist in fetal and adult
      tissues. It can reproduce itself (undergo self-renewal) or give rise to more
      specialized (differentiated) cells. Under certain inducing conditions, adult stem
      cells can acquire the ability to differentiate into different tissue cells.
      Multipotent adult progenitor cells (MAPC), an alternative name of adult stem cell
      given by Catherine Verfaillie, existing in bone marrow, can differentiate into
      cells with characteristics of mesodermal, neuroectodermal, and endodermal
      lineages in vitro at the single-cell level. MAPC can also contribute to most cell
      types when injected into the blastocyst. Adult stem cell differentiation implies
      that different cell lineages are derived from a single initial cell; all
      differentiated cell types are functional in vitro and in vivo; and engraftment is
      robust and persistent in the physiological and pathological situations. The
      possible mechanisms may underlie the differentiation: various tissue-specific
      stem cells are present in different organs; adult stem cells would be
      reprogrammed when removed from their usual microenvironment and introduced into a
      different niche that imparts signals to activate a novel genetic program needed
      for the new cell fate. And true multi-potential stem cells persist in postnatal
      life. In the future, multi-potent adult stem cells might then be used for
      therapies of degenerative or genetic disorders of multiple different organs.

PMID- 15972120
TI  - [Cytogenetic and clinical study of Philadelphia chromosome positive adult acute
      leukemia].
AB  - To explore the cytogenetics and related clinical characteristics of adult acute
      leukemia with Philadelphia chromosome positive (Ph(+)AL), MIC classification by
      morphology, immunology and cytogenetics was used to retrospectively study 79
      patients with Ph(+)AL hospitalized in the Institute of Hematology, People
      Hospital in Beijing from October 1991 to September 2003. The results showed that
      6.9% cases were diagnosed as Ph(+)AL and classified into three subtypes: acute
      lymphoblastic leukemia (Ph(+)ALL) in 56 patients (18%), acute myeloid leukemia
      (Ph(+)AML) in 10 patients (1.2%) and mixed acute leukemia (Ph(+)MAL) in 13
      patients. B-cell antigen expression was found in 52 out of 56 patients with
      Ph(+)ALL. 54.4% (43/79) patients had additional chromosome abnormalities
      including chromosome 7, double Ph and plus 8, etc. Complete remission (CR) rate
      of Ph(+)ALL and Ph(+)MAL was 57.0%, none of Ph(+)AML achieved CR. Median overall
      survival of Ph(+)ALL, Ph(+)MAL and Ph(+)AML were 10, 10 and 2.5 months
      respectively. It is concluded that Ph(+)AL has highly heterogeneity involving
      various differentiated stages of immature leukemic cells. Since the poor
      prognosis associated with this kind of AL, early diagnosis with MIC
      classification is a prerequisite to take more effective conditioning regimen and
      prospectively consideration of allogeneic stem cell transplantation to improve
      prognosis.

PMID- 15972121
TI  - Impact of trisomy 8 on cytobiological and clinical features of acute
      myelomonocytic and monocytic leukemia.
AB  - To evaluate the impact of trisomy 8 on cytobiological and clinical features of
      acute myelomonocytic and monocytic leukemia (M(4), M(5)), a total of 56 cases of
      acute myelomonocytic and monocytic leukemia were investigated. Karyotypes were
      analyzed by G-banding or R-banding. The immunotypes in all cases were detected by
      flow cytometry. And the clinical characteristics at the first visit were analyzed
      retrospectively. The results showed that thirty-four of 56 (60.7%) patients had
      normal cytogenetics; 10 (17.9%) patients had trisomy 8 in their karyotypes,
      including 3 (5.4%) patients with trisomy 8 as the sole aberration; and 12 (21.4%)
      patents had other cytogenetic abnormalities (except trisomy 8). All trisomy 8
      cases demonstrated a increased expression frequency of surface markers of myeloid
      progenitor cells CD34 (P < 0.01) and CD117 (P < 0.05) and a decreased expression
      frequency of surface markers of mature monocytes CD11c (P < 0.01) and CD14 (P <
      0.05), compared with normal cytogenetics cases. Patients with trisomy 8 were
      slightly older (P < 0.05), which had lower percentages of peripheral blasts (P <
      0.05) and lower WBC (P < 0.05) than the patients without trisomy 8. Patients with
      trisomy 8 had a shorter disease-free survival time than that of patients with
      normal cytogenetics (P < 0.05). It is concluded that trisomy 8 may play an
      important role in the pathogenesis and progression of acute
      myelomonocytic/monocytic leukemia (M(4)/M(5)), whic seems to be related with a
      block in differentiation of monocytes. Therefore, trisomy 8 may be an adverse
      prognostic factor for patients with M(4) or M(5).

PMID- 15972122
TI  - [Effect of GPI-PLD on adhesion function of bone marrow mononuclear cell from
      patients with myeloid leukemia and its mechanism].
AB  - To explore the effect of glycosyl-phosphatidyl inositol-specific phospholipase D
      (GPI-PLD) on the adhesion function of bone marrow mononuclear cell from patients
      with myeloid leukemia and analyze its mechanism, the activity of GPI-PLD in bone
      marrow mononuclear cell from the patients were measured by using GPI-anchored
      placental alkaline phosphatase (PLAP) as substrate and Triton-X114 partitioning;
      the adhesion rate and CD24 expression of these cells were measured by MTT and
      immunohistochemical method respectively, when these cells were or were not
      treated by 1 mmol/L 1,10-phenanthroline for 5 hours. The results showed that the
      GPI-PLD activity of bone marrow mononuclear cells from the patients was
      significantly inhibited after being treated by 1 mmol/L 1, 10-phenanthroline for
      5 hours [(42.08 +/- 7.21)% vs (5.4 +/- 2.96)%], while the adhesion rate and the
      expression of CD24 of these cells were increased [(49.78 +/- 26.73)% vs (61.19 +/
      29.14)%, (16.02 +/- 9.68)% vs (18.5 +/- 11.14)%, respectively)]. It is concluded
      that depression of GPI-PLD activity can increase the adhesion rate of bone marrow
      mononuclear cells from the patients while the CD24 expression is enhanced.

PMID- 15972123
TI  - [Effects of berbamine on K562 cells and its mechanisms in vitro and in vivo].
AB  - To elucidate the antileukemi effects of berbamine and the possible molecular
      mechanisms in vitro and in vivo, MTT method was used to examine the effect of
      berbamine on K562 cell growth. The apoptosis rate was measured by flow cytometry.
      The mRNA expression level of BCR/ABL gene (semiquantity value) was determined by
      RT-PCR and the BCR/ABL protein (P210) level was detected by Western blot. The
      K562-bearing mice were used to reveal the therapeutic effect in vivo. The results
      showed that a significant time- and concentration-dependent inhibition of cell
      growth was found in the cells treated with berbamine. After the cells were
      exposed to 8.0 microg/ml berbamine for 24, 48 and 72 hours, the percentage of
      growth inhibition of K562 cells progressively increased by (26.63 +/- 3.57)%,
      (61.84 +/- 4.74)%, (75.32 +/- 1.95)%, respectively (compared with control, P <
      0.01). The IC(50) (72 hours) value was 5.227 +/- 1.307 microg/ml. The apoptosis
      rate of K562 cells treated with 8.0 microg/ml berbamine for 24 and 72 hours
      increased from (29.20 +/- 3.82)% to (61.77 +/- 4.35)% (P < 0.01). Berbamine down
      regulated the expression levels of bcr/abl gene and P210 in K562 cells in a time-
      and concentration-dependent manner. The bcr/abl expression decreased from (1.38
      +/- 0.02) to (0.97 +/- 0.01) after exposure of the cells to 8.0 microg/ml
      berbamine for 0 and 72 hours (P < 0.01). When the cells were treated with 4.0 -
      16.0 microg/ml berbamine for 24 hours, the level of P210 decreased from (0.95 +/-
      0.03) to (0.63 +/- 0.01) (P < 0.01). In vivo, after treatment for 4 weeks, the
      tumor weight of berbamine-treated group was also lower than that of untreated
      group [(1.46 +/- 0.43) g vs (2.90 +/- 0.94) g, P < 0.01] and the inhibition rate
      was 49.66%, moreover, berbamine down-regulated the expression level of bcr/abl
      gene of tumor cells. It is concluded that berbamine can obviously inhibit the
      cell proliferation and induce apoptosis in K562 cell lines in a time- and
      concentration-dependent manner in vitro. The mechanisms of berbamine-induced
      apoptosis may be involved in down-regulation of bcr/abl gene expression and P210
      level. In vivo, berbamine can aslo display a better antileukemic effect and down
      regulate expression of bcr/abl gene. Berbamine extracted from Chinese herb may be
      a promising candidate of new drug for clinical anticancer treatment, especially
      for bcr-abl(+) diseases.

PMID- 15972124
TI  - [Role of Bcl-xL in the cathepsin D-associated apoptosis of K562 cells].
AB  - The purpose of study was to explore the possible functions of Bcl-xL in the
      glucosamine sulfate-induced apoptosis of chronic myeloid leukemia K562 cells.
      Light microscopy and Wright-Giemsa staining were used to investigate the
      morphologic evidences for apoptosis of K562 cells induced by glucosamine sulfate
      (GS); immunofluorescence was used to observe the translocation of cathepsin D and
      cytochrome C during the apoptosis; Western blot was performed to detect the
      expression of Bcl-xL, Bid, Bax in K562 cells treated by GS. The results showed
      that many vacuoles were observed in the cytoplasma of the K562 cells treated by
      GS; fluorescent signals of cathepsin D and cytochrome were fransformed from
      granules to disperse form by using immunofluorescence; the expression of Bcl-xL
      was found down-regulated in K562 cells treated by GS, but not in the cells pre
      treated with pepstatin A; the significant changes were not detected in expression
      of Bax and Bid protein before or after apoptosis. It is concluded that Bcl-xL
      protein may mediate relationship between cathepsin D and mitochondia pathway,
      Cathepsin D may play an important role in the GS inducing apoptosis of K562 cells
      through downregulation of Bcl-xL expression.

PMID- 15972125
TI  - [Damage effect of hepatocytic growth-promoting substance from neonatal calf on
      DNA of HL-60 cells].
AB  - The present study was aimed to investigate the damage effect of hepatocyte growrh
      promoting substance (HGS) on the HL-60 cell DNA in vitro and to explore the
      possible mechanism underlying the effect. Experiment was divided into 3 groups:
      one was control group, in which 0.9% NaCl solution was added, and other two were
      experimental group 1 and group 2, where 22.5 microg/ml and 40 microg/ml HGS were
      added, respectively. HL-60 cell growths were compared between groups with and
      without HGS. Single cell gel electrophoresis (SCGE) was used to detect DNA damage
      of HL-60 cell. DNA electrophoresis was used to detect the apoptosis of HL-60
      cells caused by HGS. The results showed that the inhibitory effects of HGS on
      growth of HL-60 cells were observed in group with 22.5 microg/ml and group with
      40 microg/ml after culture for 2 days, the DNA ladder and the apoptosis of HL-60
      cells occurred in these 2 groups on day 2 after addition of HGS, the counts of HL
      60 cells with comet tail in these experimental groups were found to be more
      increased in comparison with control group. In conclusion, the HGS can inhibit
      the growth of HL-60 cell and the apoptosis of HL-60 cells should be induced
      through pathway of DNA damage caused by HGS.

PMID- 15972126
TI  - [Effect of realgar on expression of survivin in leukemia cell lines and its
      significance].
AB  - To study the effect of realgar on expression of survivin in leukemia cell lines,
      HL-60 and Jurket cell lines were used as in vitro models. The expression of
      survivin was detected by Western blot analysis and immunofluorescence, and the
      expressions of Fas and caspase-3 were examined by immunohistochemistry. The
      results showed that the expression of survivin was positive in the two cell
      lines. HL-60 cells did not express Fas and caspase-3, and Jurket cells were Fas
      positive and caspase-3 was negative. Realgar induced a dose- and time-dependent
      down-regulation of survivin expression in Jurket cells, and especially in HL-60.
      Caspase-3 expression changed from negative to positive in HL-60 cell, but there
      still was no expression in Jurket cell. It is concluded that survivin expression
      level decreased during leukemia cell apoptosis induced by Realgar. The down
      regulation of survivin expression may be an important mechanism in leukemia cell
      apoptosis induced by realgar through mitochondrial pathway.

PMID- 15972127
TI  - [Experimental study on apoptosis in leukemia cells induced by econazole].
AB  - To investigate apoptosis of mouse leukemia cell (WEHI-3) induced by econazole and
      its mechanism, apoptosis induced by econazole was examined by flow cytometry,
      while free calcium ([Ca(2+)]i) was determined by Fura-2 fluorescein load
      technique. The protein was isolated from endoplasmic reticulum of WEHI-3 cells,
      and then the expression of caspase-12 and caspase-7 was evaluated by Western
      blot. The results showed that WEHI-3 exhibited typical change of apoptosis when
      it was treated by econazole, [Ca(2+)]i was significantly higher in comparison
      with the control. The expression of caspase-12 and caspase-7 enhanced as the
      econazole concentration increased. In conclusion, econazole can induce WEHI-3
      cell apoptosis and the caspase-12 plays a key role in this process.

PMID- 15972128
TI  - [Effects of FLAG regimen in treatment of refractory or relapsed acute myeloid
      leukemia].
AB  - In order to evaluate the effects of FLAG regimen in treatment of refractory and
      relapsed acute myeloid leukemia (AML), 27 patients with refractory or relapsed
      acute myeloid leukemia (10 refractory AML patients, 17 relapsed AML patients)
      were treated with FLAG regimen. The results show that the rate of complete
      remission was 48.2% (13/27), the rate of partial remission was 14.8% (4/27), and
      the overall response rate was 63.0%. Main toxicities were gastrointestinal side
      effectes, myelosupression and neutropenia. It is concluded that FLAG regimen can
      be employed in treatment of the refractory or relapsed patients who were not
      respond to other regimen, and the regiment was safe.

PMID- 15972129
TI  - [Effect of rat mesenchymal stem cells on hematopoietic reconstitution after
      allogeneic co-transplantation with bone marrow].
AB  - To investigate effects of rat bone marrow mesenchymal stem cells (rBMMSC) on
      hematopoiesis after allo-hematopoietic stem cell transplantation (HSCT),
      allogeneic BMT model from Fischer 344 rats (RT-1Al) to Wistar rats (RT-1Au) was
      established; effects of MSCs on hematopoietic reconstitution were studied by
      survival rate, peripheral blood counts, histological analysis and FACS at day 30
      after transplantation. The results showed that (1) MSCs from donor Fisher344
      could survive in recipient irradiated by lethal dose and could be found in the
      thymus, spleen and bone marrow of the recipient at 30 days after
      cotransplantation with BM by measuring EGFP gene. (2) Cotransplanation of MSCs
      and BM improved hematopoietic reconstitution. Lymphocyte and platelet counts of
      peripheral blood in cotransplantation group were higher than those in the control
      group. Active hematopoiesis and increase of bone marrow nucleated cells were
      observed in cotransplantation group. MSCs significantly enhanced hematopoiesis of
      B lymphocyte and megakaryocytopoietic lineages by FACS analysis. It is concluded
      that (1) MSCs of Fisher344 can be found in the thymus, spleen, bone marrow of the
      recipients at 30 days after cotransplantion by measuring EGFP gene. (2)
      hematopoietic reconstitution is significantly enhanced by MSCs cotransplanted
      with BM.

PMID- 15972130
TI  - [Effect of bone marrow mesenchymal stem cells on acute graft versus host disease
      and graft versus leukemia after allogeneic bone marrow transplantation].
AB  - To investigate the effect of bone marrow mesenchymal stem cells (BMMSC) on acute
      graft versus host disease (aGVHD) and graft versus leukemia (GVL) after
      allogeneic bone marrow transplantation (allo-BMT), both bone marrow cells and
      BMMSC obtained after three to four weeks of culture from donor mice were
      transplanted into the recipient mice injected with acute lymphocytic leukemia
      cells 5 days before, the control group was injected with bone marrow cells alone.
      The survial time after allo-BMT was recorded; the general manifestation and
      pathological changes of aGVHD in recipient mice were observed; the effects of
      BMMSC on the quatity of CD4(+) and CD8(+) T cell in vivo after allo-BMT were
      evaluated by flow cytometry; chimerism was detected by sex chromosome. The
      results showed BMMSC could increase obviously the survival time, and delay onset
      of aGVHD, BMMSC could decrease the amount of CD4(+) T cell and increase CD8(+) T
      cell in vivo. It is concluded that cotransplantation of bone marrow cells with
      BMMSC from the same donor mice has GVL effect. BMMSC can alleviate aGVHD and
      maintain GVL effect after allo-BMT.

PMID- 15972131
TI  - [Study on bone marrow transplantation camouflaged with methoxy polyethylene
      glycol].
AB  - To explore the effect of bone marrow camouflaged with methoxy polyethylene glycol
      (mPEG) on allogeneic bone marrow transplantation, 60 BALB/c(H-2d) mice were
      randomly divided into 3 groups after irradiation by 8.0 Gy of (60)Co gamma ray. A
      group was given RPMI 1640 0.5 ml in tail vein. B group was infused with the bone
      marrow cells (1 x 10(7)) mixed with the spleen cells (1 x 10(7)) of donor 615(H
      2k) mice. C group was transplanted with same dose cells, which were camouflaged
      with mPEG before infusion. Severity GVHD was determined by total manifestation of
      mice, survival rate, survival time and histo-pathological microscopy, and
      engraftment of allogeneic bone marrow was evaluated by chromosome examination.
      The results showed that 75% mice in B group had severe adverse manifestations,
      such as hunched posture, diarrhea and loss of hair. Occurrence of the same
      adverse manifestations in C group was 35% and significantly lower than that in B
      group (P <or= 0.05). The mean survival time and survival rate of C group were
      16.1 days and 50% respectively, which were higher than those of B group (12.1
      days and 20%). White blood cells in peripheral blood of C group mice recovered
      more quickly than that in B group mice. The number of GVHD grad III in B group
      was 59%, whereas in C group was 20% (chi(2) = 3.844, P = 0.050); allogeneic bone
      marrow was successfully engrafted in B and C groups. In conclusion, GVHD of
      allogeneic bone marrow transplantation can be alleviated by bone marrow cells
      camouflaged with mPEG, and such transplantation may be able to prolong survival
      time and increase survival rate.

PMID- 15972132
TI  - [Clinical study on anti-leukemia effect mediated by dentritic cells].
AB  - Immunotherapy of tumor is extensively attentioned as an important part of
      combined therapy of tumor in recent years. Dendritic cell (DC) is the most
      powerful antigen presenting cell (APC) by now which not only activates auto
      immunity to attack tumor cells, but also does help to enhance antitumor effect
      for allogenic bodies. To explore the feasibility and safety of clinical therapy
      application of peripheral blood derived DC cultured ex vivo, and analyze the
      influence of DC-inducing-immunotherapy upon long-term survival of ANLL patients
      accepted autologous bone marrow transplantation, peripheral blood mononuclear
      cells (PBMNC) of 13 ANLL patients after autologous bone marrow transplantation
      were collected by using CS3000Plus. DC immunotherapy was administered after
      cultivation of PBMNC ex vivo for 2 weeks, desease-free survival time was observed
      after therapy for long time follow-up. The results showed that no any severe
      adverse event associated with DC therapy was observed, the survival analysis of
      Kaplan-Meier suggested that five year survival rate was 75.52% in DC group while
      45.71% in non-DC group. DC group surpassed non-DC group in accumulative survival
      rate. It is concluded that the ex vivo cultivation and clinical therapy
      application of DC derived from peripheral blood are feasible and safe, DC
      immunotherapy in patients with acute non-lymphocytic leukemia after autologous
      bone marrow transplantation prolongs desease-free survival time and enhances long
      term survival rate.

PMID- 15972133
TI  - [Study on biological characteristics of cultured rhesus mesenchymal stem cells].
AB  - This study was aimed to isolate and culture rhesus mesenchymal stem cells (MSC),
      and to analyze its phenotype and biological characteristics. Bone marrow was
      aspirated from femur of rhesus, mononuclear cells were extracted, the nonadherent
      cells were removed after 24 hours, adherent cells were subcultured when they grew
      80% confluence. After the fifth passage, the cells were used for examination. The
      phenotypes of MSC were analyzed by flow cytometry, differentiated cells were
      identified by relevant specific staining. Cytokines' mRNA expressed by MSC were
      detected by RT-PCR. The results showed that rhesus MSC gave rise to a population
      of adherent cells characterized by the presence of a predominant cell type with a
      typical fibroblast-like morphology. During the log phase of growth, MSC
      proliferated to a two-fold population at 31 - 40 hours. MSC could be ex vivo
      expanded by successive cycles of trypsinization, seeding, and culture. The
      phenotypes expressed on rhesus MSC were Flk-1, CD29, CD105, CD166 positive and
      CD34, CD45, CD33 nearly negative. In various induction differentiation
      conditions, rhesus MSC could differentiate into the osteoblast and lipocyte. IL
      6, TGF-beta were highly expressed, TNF-alpha was lowly expressed and IL-2, Fas-L,
      IFN-gamma were not detected on rhesus MSC using RT-PCR method. It is concluded
      that rhesus MSC can be successfully isolated and culture-expanded and the
      biological characteristics of rhesus MSC are similar to those of human MSC.

PMID- 15972134
TI  - [In vitro expansion of cord blood mononuclear cells supported by fetal bone
      marrow stromal cells and cytokines].
AB  - This study was aimed to explore the role of human fetal bone marrow stromal cells
      (FBMSC) in combination with exogenous cytokines in supporting the in vitro
      expansion of cord blood mononuclear cells and the expression of CXCR4(+) and
      CD49d(+) in CD34(+) cells. Mononuclear cells (MNC) separated from cord blood (CB)
      were cultured in a serum-free support culture system with FBMSC or exogenous
      cytokines or both of them. On day 0, 6, 10 and 14, total cells were counted,
      CD34(+), CD34(+)CXCR4(+) and CD34(+)CD49d(+) cells were quantitated by FACS, and
      hematopoietic progenitor cells were assessed by semisolid culture assay. The
      results showed that after culturing for 14 days, CD34(+) cells, CD34(+)CXCR4(+)
      cells, CD34(+) CD49d(+) cells and colony forming unit (CFU) were significantly
      increased (P < 0.05). Compared with other groups, expansion multiple of CD34(+),
      CD34(+)CXCR4(+), CD34(+)CD49d(+) cells and CFU were higher than that in FBMSC and
      cytokine group (P < 0.05). It is concluded that the culture system used in this
      study can not only support the expansion of CB MNCs but also increase the number
      of hematopoietic stem and progenitor cells which has chemokine and adhesion
      capacity. This culture system may be a feasible way for in vitro culture of cord
      blood cells.

PMID- 15972135
TI  - [Expansion of erythroid progenitors and CD34+ cells by umbilical cord blood
      mononuclear cells].
AB  - Cord blood represents a large source of hematopoietic stem/progenitor cells. It
      can be induced to proliferate directly into erythroid progenitors in a
      appropriate ex vivo culture condition, then to generate mature red blood cells
      after injection into the body. The combination of Flt3 ligand, TPO, SCF and EPO
      is ideal for cord blood MNC to proliferate into erythroid progenitors. This study
      was aimed to evaluate the effect of FL, SCF and TPO on CD34(+) expansion. and to
      investigate influence of the cytokine combination on the proliferation of the
      CD34(+) cells. Mononuclear cells (MNC) were cultured in serum-free liquid culture
      system. Experiments were divided into 3 groups. In the group A as control no
      cytokines were added in the culture system; in the group B the cells cultured
      with SCF + FL + TPO + EPO + IGF-1; in the group C the cells were cultured with
      SCF + FL + TPO. EPO and IGF-1 were added at day 6. Part of the renewed MNCs and
      colony-forming units were counted, the proportion of CD34(+), CD34(+) CD71(+),
      CD71(+) GPA(+) cells was detected by FACS. The result showed that after 10 days,
      the the total cord blood cells increased 6.89-folds in group B and 3.06-folds in
      group C (P < 0.05). The CD34(+) cells increased 4.83-folds in group B and 2.47
      folds in group C (P < 0.05). The colony-forming cells (CFCs) increased 4.3-folds
      in group B and 2.5-folds in group C (P < 0.05). Erythroid progenitors (BFU-E) and
      CFU-E increased 5.4-folds in group B and 3.1-folds in group C (P < 0.05). The
      CD34(+)CD71(+) cells increased 8.72-folds in group B and 3.37-folds in group C (P
      < 0.05). The CD71(+) GPA(+) cells increased 53.4-folds in group B and 30.29-folds
      in group C. They were different at any time point (P < 0.05). It is concluded
      that in the group with FL + SCF + TPO, CD34(+) cells and CFC can greatly be
      expanded from cord blood MNC in the serum-free culture system. In the group with
      FL + SCF + TPO + EPO + IGF-1, erythroid progenitors can greatly be expanded in
      the serum-free culture system, supplying EPO at day 0 was better than supplying
      at day 6. Since the largest number of colony-forming cells such as BFU-E and CFU
      E were gained in the TPO + SCF + FL + EPO + IGF-1 group at day 10, the harvest
      time after cultivation in vitro should be selected at day 10.

PMID- 15972136
TI  - [Study of triptolide-induced apoptosis in MUTZ-1 cells and its allied mechanism].
AB  - To investigate the apoptotic effect of triptolide on MDS cell line MUTZ-1 cells
      and its mechanism, MUTZ-1 cells were incubated with indicated concentrations of
      triptolide. The growth of MUTZ-1 cells was observed by MTT assay and apoptosis
      was detected by DNA fragmentation analysis and flow cytometry using Annexin V
      FITC/PI staining. The gene and protein expressions were determined by reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot, respectively.
      The results showed that MUTZ-1 cell viability in presence of triptolide decreased
      markedly in a dose- and time-dependent manner. The growth-inhibitory IC50 value
      for triptolide treatment was 55.06 ng/ml. A DNA ladder pattern of
      internucleosomal fragmentation was observed. The translocation of
      phosphatidylserine at the outer surface of the cell plasma membrane could be
      induced by triptolide and its level increased following the augmentation of the
      drug concentration. Treatment of MUTZ-1 cells with triptolide for 12 hours
      resulted in the activation of caspase-3, cleavage of PARP and decrease of c-IAP2
      mRNA. The expressions of pro-caspase 3 and c-IAP2 were inversely correlated with
      the incidence of apoptosis. (r = -0.907, P = 0.000; r = -0.919, P = 0.000
      respectively). In conclusion, Triptolide inhibits MUTZ-1 cell growth by inducing
      apoptosis. The apoptotic effect of triptolide in MUTZ-1 cells is mediated by the
      caspase-3 activation and PARP cleavage. Moreover, the activation of caspase-3 may
      be associated with the down-regulation of c-IAP2.

PMID- 15972137
TI  - [Short-term curative effect of amifostine combined with rhEPO on aged patients
      wilh myelodysplastic syndrome].
AB  - The aim of this study was to investigate the curative effect of amifostine (AMF)
      combined with recombinant human erythropoietin (rhEPO) on the aged patients with
      myelodysplastic syndrome. Two aged MDS patients (one aged 91; another 86) were
      treated with amifostine and rhEPO over a period of 4 weeks. The results showed
      that a short-term curative effect was observed and transfusion interval was
      prolonged in both patients after 4 week treatment with 5 x 0.4 g AMF plus 3 x
      6,000 U rhEPO per week. The reticulocyte count in MDS-RA patient returned to
      normal at first week of treatment and still remained in normal level for 4 weeks;
      leukocyte, hemoglobin and platelet values in peripheral blood of MDS-RCMD patient
      obviousby increased, the abnormally increased reticulocyte value displayed a
      decrease trend after amifostine plus rh-EPO treatment. In conclusion, amifostine
      plus rhEPO may have a good therapeutic effect for aged MDS patients, and its
      clinical long-term curative effect still needs further evaluation.

PMID- 15972138
TI  - [Expression of the neopterin in serum and urine of the patients with non
      Hodgkin's lymphoma].
AB  - To explore the relationship between the experimental parameters including the
      neopterin (Npt), LDH and beta(2)-MG concentrations in serum or urine and the
      therapeutic effect on non-Hodgkin's lymphoma (NHL). Npt, LDH and beta(2)-MG
      levels in serum and urine collected from 27 patients with NHL before and after
      chemotherapy were measured by ELISA, biochemistry analyzer and RIA. The
      relationship between the concentrations of the Npt, LDH, beta(2)-MG in serum or
      urine and the therapeutic effect of follow-up of NHL cases were analysed. The
      results indicated that the levels of serum and urine Npt and serum LDH, beta(2)
      MG concentrations of pre- and post-chemotherapy in CR and PR patients were lower
      than that in NC and PD patients (P < 0.05). In conclusion, Npt levels of serum
      and urine and serum LDH, beta(2)-MG before chemotherapy can be used as prediction
      parameters of the therapeutic effect on NHL and the assay for Npt from the urine
      is more convenient than that from the serum.

PMID- 15972139
TI  - [Activation of platelet-neutrophil mediated by platelet-activating factor].
AB  - To investigate the pathophysiological mechanisms for platelet-neutrophils cross
      talk mediated by platelet-activating factor (PAF) and to lay a foundation for
      clinical application, ginkgolides B (GB), a PAF receptor antagonist, was added in
      the whole blood to block the effects of PAF on activation of platelet-neutrophil;
      PAF and ADP were respectively added in the whole blood to monitor the expression
      of CD62P on platelet by flow cytometry; PAF and ADP were added in the whole blood
      to monitor the expression of CD11b on neutrophil by flow cytometry; PAF and ADP
      were added in the whole blood to monitor the platelet-leucocyte aggregates (PLA)
      which were PLA in the total leucocyte population (PLA/L) and the mean
      fluorescence intensity (MFI) of CD42b. Outcomes were analyzed by t-test, and the
      differences were statistically significant (P < 0.05). The results showed that
      the expression of CD62P on platelats, the expression of CD11b on neutrophils and
      PLA formation were all increased by PAF and ADP; the PAF receptor antagonists
      (GB) could obviously inhibit the expression of CD62P, CD11b and PLA formation
      induced by PAF, but could not completely inhibit the activation of platelet and
      neutrophil, and the platelet-neutrophil cross talk; GB could inhibit the
      expression of CD62P and CD11b induced by ADP, but could not conpletely inhibit
      the activation of platelet and neutrophli; GB could not obviously inhibit the
      platelet-leucocyte aggregates mediated by ADP. It is concluded that the
      multiligand-receptor systems involved in PLA formation and platelet-netrophils
      cross talk seem to be regulated by complex mechanisms; the PAF receptor
      antagonists (GB) obviously inhibit the effect of PAF, and may be widely utilized
      in the therapy of thrombosis and inflammation.

PMID- 15972140
TI  - [Study on platelet activated state and platelet activated function in adults with
      acute leukemia].
AB  - To investigate the changes of platelet activated state and platelet activated
      function by trace whole blood flow cytometry (FCM), and to explore the mechanism
      of hemorrhage and infiltration in adults with acute leukemia, the expression
      percentage and changes of these expressions of CD62p and PAC-1 on platelet
      surface were determined by FCM of trace whole blood after platelet activated by
      ADP in patients with new diagnosed AL (group I), complete remission (CR, group
      II) and continuously complete remission (CCR, group III). Healthy adults were
      used as control group. The result showed that the expression of CD62p in group I
      and II was higher than that in control group, before and after platelet activated
      by ADP (P < 0.01). The expression of PAC-1 in group I was higher than that in
      control group (P < 0.01), the expression of PAC-1 in group II was lower than that
      in control group (P > 0.01), There was no significant difference in expression of
      CD62p and PAC-1 between group III and control group (P > 0.01), and no
      significant difference was found between AL group with megakaryocyte malignant
      pathological changes and AL group without megakaryocyte malignant pathological
      changes before platelet activated by ADP (P > 0.01). After platelet activated by
      ADP, the expression of PAC-1 in the former was lower than that in the latter (P <
      0.01). It is concluded that (1) high level activated platelet in peripheral blood
      of AL patients show that interaction between activated platelet and leukemia
      cells can be one of reason resulting in widespread hemorrhage and infiltration AL
      patiens; (2) the decrease of number and activted function of platelet at the
      first stage of AL patients may be caused by malignant hyperplasia of leukemia
      cells and damage of megakaryopoiesis in bone marrow.

PMID- 15972141
TI  - [Therapeutic effect of compound danshen solution on hemorrhagic shock combined
      with coagulopathy in rats].
AB  - To investigate the effects of complex danshen solution and heparin on the changes
      of blood coagulation factors in rats with hemorrhagic shock, and to explore the
      therapy of coagulopathy by compound danshen solution, the rat model of
      hemorrhagic shock was set up, 40 SD rats were randomized into four groups: sham
      operation, shock, compound danshen solution and heparin groups, each group was
      composed of 10 SD rats. Plasma SFMC, TM, ATIII, D-D, t-PA, PAI levels and APTT
      were detected, incidences of bleeding complications between heparin and danshen
      group were compared. The results showed that plasma SFMC, D-D levels in shock
      group were higher but ATIII level in shock group was lower than that in sham
      operation group, compound danshen solution group and heparin group (P < 0.001),
      TM levels obviously increased in shock group and heparin group (P < 0.001). There
      was no significant difference between compound danshen solution and sham
      operation groups. Plasma t-PA, D-D levels obviously increased after shock for 2
      hours, PAI level reached the peak after shock for 4 hours, but t-PA decreased.
      After shock for 6 hours, plasma PAI descended, t-PA continually drop in, but PAI
      and D-D remained in higher levels. Plasma D-D level in heparin group was lower
      than that in shock group, t-PA level was higher than that in shock group, but
      there was no significant difference between in heparin and shock groups. Plasma t
      PA, PAI and D-D levels in compound danshen solution group were lower than that in
      shock group. APTT of danshen group was lower than that of shock group and heparin
      group. Bleeding incidences was 30% in heparin group and 0% in danshen group,
      respectively. It is concluded that compound danshen solution may used to treat
      hypercoagulation and hyperfibrinolysis. In comparsion with heparin, danshen
      posses-ses advantages of safety with less bleeding complication and needs not
      tight monitor.

PMID- 15972142
TI  - [Long distance vectorette PCR for detecting translocation of IgH gene in switch
      regions of patients with multiple myeloma].
AB  - Chromosomal translocations involving immunoglobulin heavy chain (IgH) locus at
      14q32 are commonly seen in multiple myeloma (MM), which may involve in
      pathogenesis and associate with prognosis. To rapidly detect the occurrence of
      translocation involving IgH locus and the fellow chromosomes and isolate the
      break points, According to the break points occured in switch regions, patents
      and references, a long distance vectorette PCR method was developed. The results
      showed that using this method, a 3.5 kb PCR product from MM cell line U266 was
      gained, each ends aligned with 11q and IgHalpha 1 switch region, respectively. It
      is concluded that LDV-PCR is effective detection technique. Detecting China MM
      patients by using this method can interpret some specific clinic statues and
      pathogenesis mechanisms, and help to find new therapy targets and to assess the
      patient prognosis.

PMID- 15972143
TI  - [Construction of pcDNA3.1(+)/A2E eukaryotic expression vector and its expression
      on K562 cell].
AB  - To construct pcDNA3.1(+)/A2E eukaryotic expression vector and obtain a stable
      expression on HLA-I negative human K562 cell, PCR technique was employed to
      amplify A2E cDNA from the multi-cistron expression vector pG/A2E carrying HLA-E
      and HLA-A2 cDNA through internal ribozyme entry site (IRES), the cDNA was
      subcloned into vector pcDNA3.1(+), thus a eukaryotic expression was constructed
      and named pcDNA3.1(+)/A2E; then, the recombinant plasmid was transferred into the
      target cells, followed by screening with G418 and limiting dilution; finally,
      flow cytometry was adopted to detect HLA-E expression on the target cells. The
      results showed that HLA-E molecules were successfully expressed on K562 cells
      transfected with pcDNA3.1(+)/A2E (27.76%) and the expression of HLA-E molecules
      was not detected on K562 cells transfected with pcDNA3.1(+). It is concluded that
      the pcDNA 3.1(+)/A2E eukaryotic expression vector was successfully constructed
      and the HLA-E molecules were expressed on K562 cells. The data presented here
      would be expected to lay a good basis for the research of the molecular mechanism
      of HLA-E function and the interaction between HLA-E and the receptor on NK cells,
      as well as the influence of the expression of HLA-E in vitro on NK cells.

PMID- 15972144
TI  - [Analysis of sequence-tagged site in bcr and abl genes by DNA pooling and dHPLC].
AB  - To investigate the relationship between the single nucleotide polymorphism (SNPs)
      of the bcr and abl gene and chronic myelogeous leukemia (CML), the 9 sequence
      tagged sites (STS) in bcr and abl gene were screened by DNA pooling and
      denaturing high performance liquid chromatography (dHPLC), and the results were
      varified by sequencing. The results showed that the polymorphism sites were
      detected in 4 out of the 9 STS fragments and there were 3 bases different from
      the reference sequence found in 3 fragments. In conclusion, the novel SNP in
      U07000 fragment shows significantly different frequencies between CML and
      controled people.

PMID- 15972145
TI  - Ex vivo induction of anti-leukemia cytotoxic T cell effect by dendritic cells
      from human umbilical cord blood cell origin.
AB  - To explore the possibility of in vitro induction of cord blood cell-derived
      lymphocytes into cytotoxic T lymphocytes (CTL) with anti-leukemia specificity,
      umbilical cord blood (UCB)-derived mononuclear cells were cultured with multiple
      cytokines to generate dendritic cells (DC) in vitro. Leukemia cells were
      irradiated with (137)Cs and activated by premature cytokines. The characteristics
      of maturation of DC were evaluated through morphology examination and flow
      cytometry. DC pulsed with leukemic antigens were co-cultured with lymphocytes.
      Cytotoxicity of the CTL to corresponding leukemic cells was measured with lactate
      dehydrogenase-release assay. The results showed that UCB-derived monocytes could
      be induced into typical DC in all of the 12 samples. Expression of immunological
      markers such as CD1a(+), HLA-DR(+), CD86(+), CD83(+) on DC were significantly up
      regulated (P < 0.05). DC presenting leukemic antigens generated leukemia-specific
      CTL with a killing rate of (44.76 +/- 17.42)% at the E:T ratio of 50:1 against
      AML cells and a killing rate of (8.50 +/- 4.25)% at the E:T ratio of 50:1 against
      ALL cells. Whereas, these CTL present almost no killing effect on the mononuclear
      cells collected from the same patients in complete remission phase. It is
      concluded that (1) it is possible to induce UCB-derived monocytes into mature DC
      with typical morphology. (2) Cord blood derived mature DC presenting leukemia
      antigen can generate leukemia-specific CTL with vigorous cytotoxic activity
      against the same leukemia blasts and low killing activity against bone marrow
      cells of the same patients in complete remission phase.

PMID- 15972146
TI  - [Regulatory effect of IL-10 on expression of tissue factor induced by IL-6 in
      peripheral blood mononuclear cells].
AB  - To investigate the role of anti-inflammatory cytokine in acute coronary syndrome
      (ACS), the effect of IL-10 on expression of tissue factor (TF) induced by IL-6 in
      peripheral blood mononuclear cells (PBMNC) were studied. PBMNC were allowed to
      culture with rhIL-10 before being stimulated by rhIL-6. One-step recalcification
      clotting time was used to evaluate procoagulant activity (PCA) of PBMNC. The
      expression and activity of TF protein were determined by ELISA and cell
      chromogenic substrate assay. The results showed that the expression of PCA, TF
      protein and its activity in PBMNC increased significantly after being stimulated
      by rhIL-6 (P < 0.01). In PBMNC, rhIL-6-induced PCA was regulated by rhIL-10 in
      different doses. This effect was associated with reduction of TF protein
      expression and activity by rhIL-10 (P < 0.01). In conclusion, IL-10 down
      regulated expression PCA and TF in PBMNC, inhibitory effect of IL-10 on
      expression and activity of PBMNC TF may be important protective mechanism for
      ACS, regulation imbalance between inflammatory and anti-inflammatory cytokines
      may be important factor participating in coronary thrombosis.

PMID- 15972147
TI  - [Expression of insulin-like growth factor receptor type I in marrow nucleated
      cells from hematologic malignancies and its anti-apoptotic effect].
AB  - To explore the expression of insulin-like growth factor receptor type I (IGF-IR)
      and its relationship to apoptosis in hematopoietic cells of MDS and AML marrow,
      bone marrow nucleated cells from 16 patients with myelodysplastic syndrome (MDS)
      and 16 patients with acute myeloid leukemia (AML) were collected for analysis,
      respectively. Another 16 normal donors' marrow samples were taken as controls.
      Immunocytochemical method (APAAP) and TdT-mediated dUTP nick end labeling (TUNEL)
      fluorescence were used simultaneously on cytospins of nucleated cells from these
      patients. Then, the ratios of IGF-IR positive cells and apoptosis cells in all
      nucleated cells were counted separately. The results showed that (1) there was a
      higher IGF-IR expression rate (56.8 +/- 14.3)% in nucleated cells of MDS marrow
      than that in normal marrow (40.4 +/- 9.6)% (P < 0.01). Also IGF-IR positive rate
      in AML marrow (86.8 +/- 13.8)% was significantly higher than that in normal
      marrow (P < 0.01). Furthermore, IGF-IR had higher expression in AML marrow when
      compared to MDS marrow (P < 0.01); (2) apoptosis in nucleated cells of MDS marrow
      (5.4 +/- 3.0)% was significantly higher than that in normal marrow (1.2 +/- 0.9)%
      (P < 0.01) and AML marrow (0.3 +/- 0.4)% (P < 0.01), while there was less
      apoptosis in AML marrow than that in normal marrow (P < 0.01); (3) apoptosis
      occurred mainly in IGF-IR negative cells (9.0 +/- 4.8)% and less in IGF-IR
      positive cells (1.4 +/- 2.4)% (P < 0.01). IGF-IR expression showed negative
      correlation with apoptosis (r = -0.852, P < 0.01); (4) IGF-IR of MDS nucleated
      cells in RAEB/RAEB-t/CMML expressed higher than that in RA/RAS (64.1 +/- 3.2% vs
      53.5 +/- 16.2%) subgroup, although no significant difference was found (P >
      0.05); and apoptosis in RAEB/RAEB-t/CMML subgroup was lower than that in RA/RAS
      cases (3.1 +/- 2.1% vs 6.4 +/- 2.8%) (P < 0.05); (5) IGF-IR positive rate in
      nucleated cells of MDS and AML marrow showed positive correlation with blast rate
      (r = 0.677; P < 0.01). It is concluded that there is overexpression of IGF-IR in
      marrow nucleated cells in MDS and AML cases. And it seems that the overexpression
      of IGF-IR may suggest some malignant proliferation tendency and suppress cell
      apoptosis through some mechanism in these malignant hematologic ailments. So,
      anti-IGF-IR will become a new approach for therapy of MDS and AML.

PMID- 15972148
TI  - [Influence of IFN-alpha on function of CML-DC in vitro and expression of
      chemokine with its receptor].
AB  - To study the influence of IFN-alpha on function of CML-DC cultured in vitro and
      expression of chemokine and its chemokine receptor, bone marrow mononuclear cells
      from 13 CML patients were cultured in the fetal calf serum culture system
      supplemented with rhSCF, rhFlt-3L for expansion system, and adding rhGM-CSF,
      rhTNF-alpha, rhIL-4, with or without rhIFN-alpha to induce DCs. After incubation
      for two weeks, the phenotypes of CML-DC were analyzed by direct
      immunofluorescence and flow cytometry. The concentration of MIP-3beta expressed
      by CML-DC in the supernatant were analyzed by ELISA. The proliferative ability of
      T cells from healthy volunteers stimulated by CML-DCs were measured by MTT assay.
      The results showed that expression of CD86, CD83, CD40, MHC-I class molecules,
      CCR7, the concentration of MIP-3beta expressed by CML-DC, and the proliferative
      ability of T cells stimulated by CML-DCs in IFN-alpha group were all
      significantly higher than that in control group (P < 0.01). It is concluded that
      the immunophenotype of CML-DCs can be partially changed by IFN-alpha to
      accelerate the maturation of CML-DCs, enhance the capacity of CML-DCs, and
      stimulate allogeneic T lymphocyte proliferation.

PMID- 15972149
TI  - [Cloning of human RHD gene and its expression in K562 cells].
AB  - The aim of this study was to clone human RHD gene and to investigate its
      expression in transduced K562 cells. Total RNA was extracted from reticulocyte of
      cord blood. RHD and RHCE genes were amplified using RT-PCR method. The amplified
      products were cloned into pGEM-T plasmid by TA ligation and several clones were
      screened by direct sequencing method in order to obtain the RHD gene. RHD gene
      was subcloned into pcDNA3.1(-) expression vector, then the recombined plasmids
      were transduced into K562 cells with superfect transfection reagent kit. Finally
      transcription and expression of RHD gene in K562 cells were detected. The result
      showed that RHD gene has been cloned sucessfully, the inserted sequence and
      direction of RHD cDNA in its recombined pcDNA3.1(-) vector were identified using
      enzyme cutting and sequencing method. After transduced with recombined pcDNA3.1(
      ) vector, K562 cells could transcribe RHD mRNA in its cytoplasm and express RhD
      antigen on its membrane surface. In conclusion, RhD antigen can expressed in K562
      cells with RHD cDNA transduction, and the expression system in vitro may be
      helpful to further investigate the molecular basis of RhD variants.

PMID- 15972150
TI  - [Collection of peripheral blood stem cells from ABO incompatible allogeneic
      donors by using blood cell separator].
AB  - To evaluate the yield of the blood cell separator for collection of peripheral
      blood stem cells (PBSC) from ABO major and (or) minor incompatible allogeneic
      donors and the feasibility of PBSC component infusion to the recipients without
      removal of erythrocytes or plasma, the Cobe Spectra (Version 6.1) blood cell
      separator was utilized to collect PBSC component from 9 allogeneic donors. Of all
      the donors, 4 were ABO major incompatible, 2 were minor incompatible and the
      other 3 were both major and minor incompatible to corresponding recipients. In
      each cycle, different amount of PBSC component was harvested, and the variable
      volume plasma chased the cells into the bag was adjusted according to the ABO
      incompatibility. The nucleated cell count, percentage of mononuclear cell, number
      of CD34(+) cell and percentage of viable cell (trypan blue excluding rate) in the
      component were detected. At the time of infusion, a series of protective measures
      to the renal function of recipients were taken. The results showed that apheresis
      was twice performed on these eight donors to collected enough PBSC for
      transplantation or cryopreservation, except one apheresis was enough for cell
      amount needed by transplantation, as the donor's body weight was much heavier
      than that of the recipient. Altogether 17 apheresises were performed, the mean
      yield of nucleated cells was 3.77 x 10(10), in which 97% to 99% were mononuclear
      cells (MNC). The harvested number of CD34(+) cell was 8.62 x 10(6)/kg. All the
      trypan blue exclusion rate was 100%. In ABO major incompatible or both major and
      minor incompatible component, there were 8 - 10 ml packed erythrocytes; in ABO
      minor incompatible component, there were 80 - 120 ml of plasma. These components
      were infused into the recipients without removal of erythrocytes or plasma and no
      haemolytic reaction was observed in any recipient, and their hematopoietic
      functions soon recovered. Results suggest that enough PBSC can be acquired by
      using blood cell separator Cobe Spectra (Version 6.1), with the modified
      separation factors, and the collected PBSC component can be safely infused into
      the ABO incompatible recipients without removal of erythrocytes or plasma.

PMID- 15972151
TI  - [Clinical significance of PML/RARalpha isoforms in adult patients with acute
      promyelocytic leukemia].
AB  - To evaluate the relation of PML/RARalpha isoforms in adult APL patients to
      clinical therapy and prognosis, the picture of blood and bone marrow aspirates
      for 71 APL patients treated by induction therapy were peridically examined and
      the different transcripts of PML/RARalpha were assayed by nested RT-PCR. The
      results showed that the median WBC count (x 10(9)/L) in the patients with the
      short (S) and variable (V) isoform were significantly higher than that in long
      (L) isoform. So, the serious bleeding complications early occurred. Relapse risk
      for patients with S and variable isoforms were higher than that with L isoform.
      In conclusion, PML/RARalpha isoforms in patients with APL may be the independent
      prognostic factor.

PMID- 15972152
TI  - [Inhibitory effect of daunorubicin enhanced by PDTC on drug-resistant leukemic
      cells in vitro].
AB  - To investigate the chemosensitizing effect of pyrroledithiocarbomate (PDTC) on
      daunorubicin in drug-resistant leukemic cells in vitro, MTT method was used to
      observe the changes of the proliferation of intractable leukemia MNC treated with
      daunorubicin (30 microg/ml) combined with PDTC (25, 50 or 100 micromol/L). The
      results showed that inhibiting rate of daunorubicin combined with PDTC(25, 50 or
      100 micromol/L) on drug-resistant leukemic cells was significantly higher than
      that of daunorubicin alone (P < 0.05). Among the three different doses of PDTC,
      the concentration of 50 micromol/L of PDTC inhibited the proliferation of drug
      resistant leukemic cells significantly. In conclusion, PDTC can sensitize anti
      tumor effect of daunorubicin in vitro. The concentration of 50 micromol/L of PDTC
      has stronger chemosensitizing effect on daunorubicin than that of the other
      concentrations of PDTC (25 micromol/L or 100 micromol/L) in vitro.

PMID- 15972153
TI  - [A case of hepatosplenic gammadelta T cell lymphoma].
AB  - Hepatosplenic gammadelta T cell lymphoma represents rare, often aggressive type
      of malignant peripheral T-cell lymphoma, which is characterized by expressing T
      cell-associated markers CD2, CD3 and gammadelta T-cell receptor, and nonactivated
      cytotoxic cell phenotype (TIA-1+, granzyme B-). The pathological findings of a
      liver biopsy specimen revealed the diffuse infiltration of lymphocytes in the
      sinusoids and the aspiration biopsy from spleen revealed the diffuse infiltration
      of lymphocytes in the red pulp, not shaped to the nodes, often resulted in the
      misdiagnosis. Recently, by analyzing the immunophenotype and TCR rearrangement
      from liver, spleen and bone marrow, a case of adult hepatosplenic gammadelta T
      cell lymphoma was diagnosed. In combination with references, It is belived that
      immunophenotype and TCR rearrangement are necessary means to diagnosis
      hepatosplenic gammadelta T cell lymphoma.

PMID- 15972154
TI  - [Study on detection of samples of Rh-weak D and Del].
AB  - To study the detection of weak D and Del from samples initially screened RhD(-),
      RhD phenotype was initially screened by routine serological test, out of which
      weak D phenotype was detected by indirect antiglobulin test (IAT) and Del
      phenotype was detected by chloroform-trichloroethylene absorption-elution test.
      The results showed that 56 samples were RhD(-) confirmed by routine serology
      test, which were screened out of 26 200 donors, among them 5 samples were typed
      as weak D by IAT and 9 cases samples were typed as Del by absorption-elution
      test. In conclusion, the samples which typed as RhD(-) by routine serological
      test must be identified by IAT and chloroform-trchloroethylene absorption test is
      order to detect weak D and Del phenotype. It is important for clinical
      transfusion safely.

PMID- 15972155
TI  - [Effect of recombinant human G-CSF combined with EPO in treatment of patients
      with MDS].
AB  - To investigate the efficaciousness of recombinant human granulocyte colony
      stimulating factor (G-CSF) combined with recombinant human erythropoietin (EPO)
      in the treatment of patients with myelodysplastic syndrome (MDS), the
      hematological changes in the blood and bone marrow along with clinical features
      after treatment with G-CSF and EPO in 15 patients were observed. Patients were
      subcutaneously injected with G-CSF 300 microg/d for 10 days, then injected with
      EPO 100 U/(kg x d) for 10 days. The results showed that the obvious improvements
      in granulocytes of blood were found in 10 patients with MDS, improvements in
      erythrocytes of blood were observed in 7 patients with MDS. No serious side
      effects occured is all treated patients. In conclusion, treatment of G-CSF in
      combination with EPO is effective for patients with MDS.

PMID- 15972156
TI  - [Progress of study on placenta mesenchymal stem cells--review].
AB  - Recently mesenchymal stem cells have been successfully obtained from various
      sources of human body, including bone marrow, compact bone, peripheral blood,
      adipose tissue, cord blood, amniotic fluid and other fetal tissues. Placenta, as
      a temporary organ keeping substance exchange between mother and fetus, consisted
      of decidua basalis and chorion frondosum, which derived from cytotrophoblast and
      extraembryonic mesoderm, thus involved both primary embryonic cells and adult
      stem cells. As a castoff after parturition, along with the ease of accessibility,
      lack of ethical concerns, placenta may be an attractive source of mesenchymal
      stem/progenitor cells for basic and clinical application. Therefore, the origin,
      isolation, characteristics and potential uses in future therapy are mainly
      reviewed in this paper.

PMID- 15972157
TI  - [Advances of study on activation of nuclear factor kappaB in hematological
      malignancies and its mechanism--review].
AB  - The nuclear factor kappa B(NF-kappaB) plays a crucial role in inflammatory,
      immune response, embryo development, cell proliferation and apoptosis, cell cycle
      control as well as tumorgenesis. In recent years, a variety of investigations
      have demonstrated that NF-kappaB was closely associated with the pathogenesis of
      hematological malignancies such as leukemia, lymphoma and multiple myeloma.
      Nowadays, increasingly attention has been paid to the studies on the activation
      and its mechanism of NF-kappaB in the hematogenic malignancies. So that, in this
      article, progress on these aspects is reviewed.

PMID- 15972158
TI  - [Progress of study on sideroblastic anemia and its possible gene therapy-
      review].
AB  - It was thought that delta-aminolevulinate synthase (ALAS) is the rate-limiting
      enzyme in the heme biosynthetic pathway. Actually there are two isozymes of ALAS
      and ALAS2 (erythroid delta-aminolevulinate synthase), they play the leading role
      in the hemoglobin biosynthetic pathway. Mutations in ALAS2 gene causes X-linked
      sideroblastic anemia (XLSA). About 25 different mutations in ALAS2 gene have been
      identified in XLSA patients and two of them were reported by our laboratory. It
      is possible to cure the patients with XLSA by gene therapy because it is a single
      gene disorder.

PMID- 15972159
TI  - [Research advances on drug resistance and anti-apoptosis of leukemic cells
      associated with bone marrow stromal cells--review].
AB  - The bone marrow microenvironment composed of bone marrow cell, their secreted
      cytokines and extra-cellular medium (ECM), plays an important role in the process
      of hematopoiesis, hematonosis, apoptosis of malignant blood cells. In this
      review, the mechanisms for the protection of the leukemiic cells from the drug
      induced apoptosis by bone marrow stromal cells and the related progress were
      summarized.

PMID- 15972161
TI  - Surgeons: employees or professionals?

PMID- 15972162
TI  - Surgical salvage of peritoneal dialysis catheters from chronic exit-site and
      tunnel infections.
AB  - BACKGROUND: Chronic exit-site and tunnel infections of the peritoneal dialysis
      catheter are significant causes of catheter loss. Surgical salvage procedures
      that can effectively resolve the infection and preserve dialysis are of major
      importance. METHODS: Thirteen patients with chronic exit-site and tunnel
      infections underwent surgical salvage consisting of unroofing the tunnel tract
      and shaving of the superficial catheter cuff. A control group of 138 patients
      implanted during the same time span as the study group was used for infection
      rate and survival comparisons. RESULTS: The salvage procedure cured the infection
      in all patients. No dialysate leaks occurred. Peritoneal dialysis was not
      interrupted. Surgical salvage provided successful long-term peritoneal dialysis
      that was equivalent to the cohort dialysis population. CONCLUSION: Surgical
      salvage by unroofing/cuff shaving is an effective long-term solution for chronic
      exit-site and tunnel infection.

PMID- 15972163
TI  - Hospitals collaborate to decrease surgical site infections.
AB  - BACKGROUND: Despite a large body of evidence describing care processes known to
      reduce the incidence of surgical site infections, many are underutilized in
      practice. METHODS: Fifty-six hospitals volunteered to redesign their systems as
      part of the National Surgical Infection Prevention Collaborative, a 1-year
      demonstration project sponsored by the Centers for Medicare & Medicaid Services.
      Each facility selected quality improvement objectives for a select group of
      surgical procedures and reported monthly clinical process measure data. RESULTS:
      Forty-four hospitals reported data on 35,543 surgical cases. Hospitals improved
      in measures related to appropriate antimicrobial agent selection, timing, and
      duration; normothermia; oxygenation; euglycemia; and appropriate hair removal.
      The infection rate decreased 27%, from 2.3% to 1.7% in the first versus last 3
      months. CONCLUSIONS: The Collaborative demonstrated improvement in processes
      known to be associated with reduced risk of surgical site infections. Quality
      improvement organizations can be effective resources for quality improvement in
      the surgical arena.

PMID- 15972164
TI  - Keeping score and the application of known principles.

PMID- 15972165
TI  - The importance of location in determining breast conservation rates.
AB  - BACKGROUND: This study evaluates differences in the utilization of breast
      conservation surgery (BCS) between major metropolitan areas in the United States
      (US) and the United Kingdom (UK). METHODS: Surgical and staging information were
      obtained from the Cancer Surveillance Program for Los Angeles County (LAC), the
      New York State (NYS) Department of Health Cancer Registry, and the UK National
      Health Service (NHS) Breast Screening Program. Demographic data were obtained
      from the census databases from the US, UK, Northern Ireland, and Scotland.
      Descriptive statistics, correlation analysis, and chi-square tests were used to
      compare rates of BCS across the locations under study. RESULTS: Breast
      conservation rates were highest in London (79.3%) compared to New York City (NYC)
      (69.7%) and LAC (66.5%) (P < .0001). Both in NYS and the UK, the cities differ
      from the surrounding regions in population density, education levels,
      agricultural activities, and unemployment. BCS rates tended to increase with
      population density and education levels, and decrease with increased unemployment
      and agricultural activity, but there was no impact on BCS rates when adjustments
      for these variables were included in regression models. BCS rates increase with
      increasing hospital case volume in LAC and NYC (P < .0001). CONCLUSION: When
      comparing large metropolitan areas in the US and UK there are significantly
      different rates of BCS in different locations. These differences reflect
      differences in population density, socioeconomic status (SES), education levels,
      hospital volume, and the effects of a nationally funded screening program.

PMID- 15972166
TI  - A prospective evaluation of ultrasound-directed transparenchymal vascular control
      with linear cutting staplers in major hepatic resections.
AB  - BACKGROUND: We prospectively evaluated a novel ultrasound-directed technique of
      major hepatic resection using transparenchymal application of vascular staplers
      intending to minimize blood loss, operative time, and hepatic warm ischemia time.
      METHODS: Beginning in 1998 many major hepatic resections for hepatic tumors were
      performed with ultrasound-directed transparenchymal application of vascular
      linear cutting staplers. An endoscopic flexible neck vascular linear cutting
      stapler was used for control of the hepatic veins. RESULTS: From December 1998 to
      April 2003, 346 patients undergoing hepatic resection using this technique were
      identified from a prospective hepatobiliary tumor surgery database. Records were
      reviewed for blood loss, transfusion requirement, inflow occlusion (Pringle
      maneuver) time, overall operative time, and perioperative and postoperative
      complications. The average blood loss for all patients was 396 +/- 28.4 mL. The
      inflow occlusion time was 13.7 +/- .64 minutes with a total operative time of
      140.7 +/- 3.7 minutes. Additional liver-related procedures were performed in 52%
      of the patients. The overall complication rate was 29.5% with a 90-day mortality
      rate of 1.4%. CONCLUSIONS: Ultrasound-directed transparenchymal application of
      vascular staplers to control inflow and outflow during major liver resection
      minimizes blood loss, warm ischemia time, and operative time compared to
      published reports of patients undergoing resection using other techniques.

PMID- 15972167
TI  - Influence of workers' compensation eligibility upon functional recovery 10 to 28
      years after polytrauma.
AB  - BACKGROUND: Previous studies have shown that work-related injuries are often
      associated with inferior outcomes. The aim of the current study was to compare
      the long-term functional outcome after polytrauma between work-related and non
      work-related injuries at a minimum follow-up of 10 years. METHODS: Six hundred
      thirty-seven polytrauma patients were evaluated using a patient questionnaire and
      a physical examination. The average follow-up was 17.5 years (range 10-28 years);
      the average Injury Severity Score (ISS) was 20.7 (range 4 to 54). RESULTS: A
      multivariate analysis, with adjustments for age, sex, injury severity, and injury
      pattern, demonstrated that work-related injuries resulted in significantly
      inferior outcomes measured by the Hannove Score for Polytrauma Outcome (HASPOC),
      12-Item Short-Form Health Survey (SF-12), requirement for medical aids and
      devices, length of rehabilitation, and retirement status (P < .05). CONCLUSIONS:
      Polytrauma patients receiving workers' compensation achieve significantly
      inferior long-term outcomes than other patients. The obtained results demonstrate
      that psychosocial variables such as insurance status have a significant impact on
      the functional recovery following polytrauma.

PMID- 15972168
TI  - Small-bowel diverticulosis.
AB  - Diffuse jejunoileal diverticulosis with pneumoperitoneum but without peritonitis
      is an uncommon but well-documented entity. Cases of jejunoileal diverticular
      perforation in which the perforation is evident are managed with resection of the
      diseased bowel and primary anastomosis. In the absence of an intraoperative
      finding of a perforation or an area of discrete inflammation, copious irrigation
      and closure of the abdomen is appropriate in cases of diffuse small-bowel
      diverticulosis.

PMID- 15972169
TI  - Incidence and outcome of complications following restorative proctocolectomy.
AB  - BACKGROUND: Complications were analyzed in 296 patients with ulcerative colitis
      who underwent restorative proctocolectomy. METHODS: In 96.3% of patients, the
      pouch was anastomosed using the double stapling method. A total of 44.6% of
      patients underwent restorative proctocolectomy in 1 stage without ileostomy and
      53% in 2 stages. Complications were divided into 2 stages: early (within 1 month)
      and late (after 1 month); moreover, the annual incidences were calculated, mean
      onset time, and pouch survival rate. RESULTS: The overall incidence of
      complications was 52.7%. Early complications (13.2%) occurred significantly less
      often than late complications (46.3%) (P < .05). Thirty-five (17.7%) of 198
      complications required surgery. The cumulative 5- and 10-year pouch survival rate
      was 99%, respectively. CONCLUSIONS: The rate of complications after restorative
      proctocolectomy was almost equivalent to that in other reports, but the pouch
      survival rate was very high.

PMID- 15972170
TI  - In-line radiofrequency ablation to minimize blood loss in hepatic parenchymal
      transection.
AB  - BACKGROUND: Intraoperative blood loss has been shown to be an important factor
      correlating with morbidity and mortality in liver surgery. A 5-cm long instrument
      with variably deployable metal electrodes using in-line radiofrequency ablation
      (ILRFA) energy was used for hepatic transection in an attempt to reduce bleeding.
      METHODS: Eight patients underwent liver resection. At each resection, half the
      resection was performed with ILRFA and the other half was performed with an
      ultrasonic aspirator alone. Blood loss was measured for each mode of resection.
      RESULTS: The mean blood loss using ILRFA was 6.5 (+/-3.7) mL/cm(2) compared with
      20.4 (+/-8.7) mL/cm(2) by using the ultrasonic aspirator (P = .004). CONCLUSIONS:
      In-line radiofrequency ablation reduced bleeding during hepatic parenchymal
      transection when compared with the ultrasonic aspirator.

PMID- 15972171
TI  - Feasibility of colectomy with mini-incision.
AB  - BACKGROUND: Laparoscopic resection has been advocated as a method of colectomy
      for various colon and rectal disease. One advantage claimed by laparoscopy is its
      smaller incision size. The aim of the present study is to evaluate whether mini
      incision is feasible along with the advantage of adequate exploration of the
      peritoneal cavity. METHODS: From December 2000 to November 2003, 316 patients
      with various colorectal diseases receiving colectomies through a skin incision
      less than 7 cm were analyzed. All of the colectomies were performed by a single
      surgeon. Exploration of the entire peritoneal cavity was possible for all the
      cases. There were 153 men and 163 women. Ages ranged from 19 to 90 years,
      averaging 62.4 years. Two hundred ninety-five patients were operated on for
      carcinoma of the colon or rectum; 4 had operations for villous tumors with severe
      dysplasia; 3 each for radiation enterocolitis and diverticulitis; 2 each for
      malignant stromal tumor and rectal prolapse; and 1 each for lymphoma,
      actinomycosis, volvulus, angiodysplasia, Crohn's disease, ulcerative colitis, and
      ovarian cancer with rectal invasion. There were 15 abdominoperineal resections,
      97 low anterior resection, 49 anterior resections, 64 sigmoidectomies, 7 left
      hemicolectomies, 81 right hemicolectomies, 2 subtotal colectomies, and 1
      restorative proctocolectomy. No Harmonic scalpel or laser was used during
      surgery. No hand-port or laparoscope was used in the series. RESULTS: Five
      patients died of acute respiratory failure, 2 patients died of terminal cancer,
      and 1 patient died of hypoglycemia due to poor control of diabetes mellitus.
      Complications included 11 urinary tract infections, 8 intestinal obstructions, 6
      anastomotic leakages, 6 wound infections, 5 respiratory failures, 5 pelvic
      bleedings, 2 pneumonias, 2 gastrointestinal bleedings, and 1 pancreatitis. Small
      incisions did not prolong operation time. CONCLUSION: This experience suggests
      that the majority of colectomies can be accomplished by an incision of less than
      7 cm, which is no larger than the incision size used in a laparoscope colectomy
      if multiple incisions made for trocars are added to the main incision length. The
      advantages of mini-incision include lower cost, faster completion of procedure,
      reduced bulkiness of equipment, and the possibility of exploring the entire
      peritoneal cavity by hand without loss of tactile sensation.

PMID- 15972172
TI  - Increasing age does not affect efficacy of sentinel lymph node biopsy using
      smaller-sized technetium-99m tin colloids for breast cancer patients.
AB  - BACKGROUND: Increasing age of breast cancer patients was reported to cause not
      only failure of sentinel lymph node (SLN) identification but also false negative
      results. METHODS: A retrospective review was conducted of breast cancer patients
      who underwent sentinel lymph node biopsy (SLNB) using small-sized technetium-99m
      labeled tin colloid (particle size: 200-400 nm in diameter). A comparison between
      82 patients who were less than 60 years and 40 patients who were > or =60 years
      of age was performed to evaluate the efficacy of SLNB using the small-sized tin
      colloid in older patients. RESULTS: One hundred twenty-two clinically node
      negative breast cancer patients underwent SLNB. Apart from age, there were no
      statistically significant differences between the younger patients and the older
      patients in terms of the clinicopathologic characteristics. Successful mapping
      rates, false negative rates, and accuracy were comparable between the 2 groups.
      CONCLUSIONS: SLNB using the small-sized tin colloid was not affected by
      increasing age.

PMID- 15972173
TI  - Hydronephrosis as a prognostic factor in pelvic recurrence from rectal and colon
      carcinomas.
AB  - BACKGROUND: After multimodal treatment estimated 5-year survival of locally
      recurrent rectal cancer is about 25%. Hydronephrosis secondary to pelvic
      recurrence of colorectal cancer is a condition claimed to represent a
      contraindication to surgery due to a dismal prognosis. METHODS: Prospective
      registration of 193 consecutive patients operated for pelvic recurrence in rectal
      or colon cancer from January 1991 until March 2002 at a tertiary referral
      hospital, 121 men and 72 women, median age 67 years, all given irradiation
      preoperatively. Twenty-three of 193 had hydronephrosis prior to preoperative
      irradiation for recurrent disease. RESULTS: R-0 stage resection was obtained in
      22% of patients with hydronephrosis and in 41% without. The median survival times
      in patients without metastasis were 27 and 32 months, respectively, and 5-year
      survival rates were 11% and 25%. CONCLUSIONS: An aggressive surgical approach
      offers patients with pelvic recurrence from rectal and colon cancer the best
      potential for survival. The presence of hydronephrosis probably indicates a lower
      chance for complete surgical resection of the recurrence, but local control and
      improved survival may still be achieved, and about two thirds of patients may
      benefit from the operation.

PMID- 15972174
TI  - Umbilical hernia repair with the prolene hernia system.
AB  - BACKGROUND: Despite its extensive application for the repair of inguinal hernias,
      the use of the Prolene Hernia System (PHS; Ethicon, West Somerville, NJ) for the
      repair of umbilical hernias has been sparse. The purpose of this prospective
      study was to assess, in comparison with currently available techniques, the
      effectiveness of the PHS in repairing umbilical hernias. METHODS: Fifty
      consecutive patients diagnosed with a primary umbilical hernia were enrolled for
      the study. They were randomized and underwent elective repair of umbilical hernia
      using either the PHS (n = 17), Mayo repair (n = 18), or onlay repair with mesh (n
      = 15). Data for the time required for the surgical repair method, length of
      hospital stay, postoperative pain, analgesic necessity, and return to work, and
      early and late complications were recorded, and compared with respect to the
      repair procedure. RESULTS: The mean operating time and the mean length of
      hospital stay were the longest in the onlay repair with mesh group (P < .05).
      Those patients operated on using the PHS described minimum pain on the
      postoperative first , second, and seventh days (P < .05) and also the necessity
      of analgesic was significantly lower in this group (P < .05). There were 2
      recurrences in Mayo repair group. The mean follow-up duration was 22 months
      (range 6 to 44 months). CONCLUSION: The PHS seemed to be useful for umbilical
      hernia repairs in selected patients as it caused minimal postoperative pain and
      less analgesic necessity.

PMID- 15972175
TI  - Vascular closure staples for portal vein reconstruction in living-donor liver
      transplantation.
AB  - BACKGROUND: Portal vein reconstruction is still a crucial problem in living-donor
      liver transplantation. Vascular closure staples (VCS) have been applied for small
      peripheral and large vessels because of the technical ease with which they can be
      employed. We describe here our experience with portal vein reconstruction in
      living donor-liver transplantation and compare VCS with conventional sutures in
      portal vein reconstruction. METHODS: The anastomosis between the donor portal
      vein and recipient portal vein or the right external iliac vein graft was created
      using either VCS or conventional sutures. RESULTS: The stenotic ratios were .51
      +/- .15 and .79 +/- .25 for the conventional sutures and VCS, respectively. The
      stenotic ratio was significantly lower in VCS compared with conventional sutures.
      CONCLUSIONS: VCS compared with conventional sutures has the advantage of low risk
      of anastomotic stenosis.

PMID- 15972176
TI  - Laparoscopic transhiatal esophagectomy for esophageal cancer.
AB  - BACKGROUND: Traditional esophagectomy may be associated with mortality,
      considerable morbidity, and lengthy recovery. It is often performed in cancer
      patients who are typically older, have associated comorbidities, and are often
      malnourished, all factors that increase surgical risk. Minimally invasive
      esophagectomy has the potential advantages of being a less traumatic procedure
      with an easier postoperative recovery and fewer wound and pulmonary
      complications. METHODS: A retrospective analysis of patients who underwent
      laparoscopic transhiatal esophagectomy was performed. Assessed parameters
      included patient demographics and operative data, pathology results, and long
      term follow-up of at least 12 months. RESULTS: Twenty-two patients underwent
      laparoscopic transhiatal esophagectomy; 19 had esophageal cancer. Two patients
      were operated on for Barrett esophagus, and 1 patient had achalasia. The majority
      of patients were men (82%), and the mean age was 59 years (range 15 to 74 years);
      1 patient (4.5%) was converted to open surgery. The average operative time was
      380 minutes (range 285 to 525 minutes), and the average blood loss was 220 mL;
      only 3 patients required transfusion. The median hospital stay was 8 days (range
      5 to 46 days). Postoperative mortality occurred in 1 patient (4.5%), and
      postoperative complications developed in 6 patients (27.2%). In the 19 cancer
      patients, the average number of harvested nodes was 14.3 (range 10 to 19). The
      average follow-up was 30 months (range 12 to 48 months). The overall survival for
      cancer patients was 61% (11 of 19), and disease-free survival was 39% (7/19).
      CONCLUSIONS: Esophagectomy is a major surgery with considerable morbidity and
      potential mortality. Minimally invasive esophagectomy is a feasible approach that
      can be safely performed by surgeons with extensive experience in that field.
      Advantages include less intraoperative blood loss, a smaller incision, and a
      potentially faster postoperative recovery. In cancer patients, immediate
      oncologic goals of adequate margins and lymph node dissection can be achieved,
      and long-term outcome appears to be similar to that found with open approaches.

PMID- 15972177
TI  - Vascular occlusion to decrease blood loss during hepatic resection.
AB  - BACKGROUND: Historically, the primary hazard with liver surgery has been
      intraoperative blood loss. This led to the refinement of inflow and outflow
      occlusive techniques. The utility of the different methods of inflow and outflow
      techniques for hepatic surgery were reviewed. METHODS: A search of the English
      literature (Medline, Embase, Cochrane library, Cochrane clinical trials registry,
      hand searches, and bibliographic reviews) using the terms "liver," "hepatic,"
      "Pringle," "total vascular exclusion," "ischemia," "reperfusion," "inflow," and
      "outflow occlusion" was performed. RESULTS: A multitude of techniques to minimize
      blood loss during hepatic resection have been studied. The evidence suggests that
      inflow occlusion techniques are generally well tolerated. These should be used
      with caution in patients with cirrhosis, fibrosis, steatosis, cholestasis, and
      recent chemotherapy, and for prolonged time intervals. CONCLUSIONS: Harmful
      effects of intraoperative blood loss and transfusion occur during hepatic
      resection. Portal triad clamping (PTC) is associated with less blood loss
      compared with no clamping. In procedures with ischemic times <1 hour in length,
      PTC-C (continuous) is likely equal to PTC-I (intermittent). In patients with
      chronic liver disease or undergoing lengthy operations, PTC-I is likely superior
      to PTC-C. PTC is superior to total vascular exclusion except in patients with
      tumors that are large and deep seated, hypervascular, and/or abutting the hepatic
      veins or vena cava and in patients with increased right-sided heart pressures.

PMID- 15972178
TI  - How much liver resection is too much?
AB  - BACKGROUND: Hepatic failure occurring after liver resection carries a poor
      prognosis and is a complication dreaded by surgeons. Inadequate reserve in the
      remaining parenchyma leads to a steady decrease in liver function, inability to
      regenerate, and progression to liver failure. For this reason, many methods to
      quantify functional hepatic reserve have been developed. METHODS: This article
      reviews the main methods used in the assessment of hepatic reserve in patients
      undergoing hepatectomy and their use in operative decision making. RESULTS: A
      range of methods to categorically quantify the functional reserve of the liver
      have been developed, ranging from scoring systems (such as the Child-Pugh
      classification) to tests assessing complex hepatic metabolic pathways to
      radiological methods to assess functional reserve. However, no one method has or
      is ever likely to emerge as a single measure with which to dictate safe limits of
      resectability. CONCLUSIONS: In the future, the role of residual liver function
      assessment may be of most benefit in the routine stratification of risk, thus
      enabling both patient consent to be obtained and surgical procedure to be
      performed, with full information and facts regarding operative risks. However,
      there is no one single test that remains conclusively superior.

PMID- 15972179
TI  - Selection of individuals for training in surgery.
AB  - Surgical training in the United Kingdom and Europe is in transition given the
      pressure to decrease the number of workweek hours and the numbers of years in
      training. To achieve this shortened training in the United Kingdom, the primary
      component will be the foundational education, which will last for 2 years, with
      the second year perhaps counting toward specialist training. It would be a
      potential advantage for achieving rapid surgical training if we could preselect
      those students with the necessary attributes of a surgeon. During the foundation
      period there is exists the question of assessment, so this might be a natural
      point at which to preselect these students. This article considers psychometric
      assessment as a methodology of preselecting surgeons and considers objective
      assessment as a possibility during the foundational education period.

PMID- 15972180
TI  - Attitudes regarding surgeons' attire.
AB  - BACKGROUND: No studies to date exist regarding the attire of physicians on a
      surgical service. The objective of this study was to determine patient, surgeon,
      and nonhospitalized public (NHP) attitudes and preferences regarding surgeons'
      attire and mannerisms. METHODS: A questionnaire was developed to survey each
      group. The Internet was used as a novel avenue to survey the NHP. Eight questions
      were presented to each group, and each question had three possible responses:
      agree, disagree, or no opinion. Total responses and percentages were determined
      for each group's answers, and statistical analysis was performed using chi-square
      test. RESULTS: Thirty-eight surgical inpatients, 38 surgeons, and 334 NHP
      participated in the study. All groups agreed that surgeons should wear nametags
      while they are seeing patients. Inpatients agreed with surgeons that surgeons
      should wear white coats while seeing patients (P > .05). Surgeons considered
      scrubs and clogs to be acceptable attire, which differed from all other groups (P
      < .05). Although 31% of the NHP considered blue jeans acceptable, only 10% of
      surgeons (P < .05) and 22% of patients (P > .05) considered them acceptable. All
      groups believed that a surgeon's appearance influences their perceptions and
      impressions regarding the quality of medical care they received (P < .05).
      CONCLUSIONS: Based on the agreement of all groups that a surgeon's appearance and
      mannerisms affects perceptions of the quality of medical care received, surgeons
      should respond to these perceptions and dress accordingly while seeing surgical
      patients.

PMID- 15972181
TI  - A global assessment tool for evaluation of intraoperative laparoscopic skills.
AB  - BACKGROUND: There is a pressing need for an intraoperative assessment tool that
      meets high standards of reliability and validity to use as an outcome measure for
      different training strategies. The aim of this study was to develop a tool
      specific for laparoscopic skills and to evaluate its reliability and validity.
      METHODS: The Global Operative Assessment of Laparoscopic Skills (GOALS) consists
      of a 5-item global rating scale. A 10-item checklist and 2 visual analogue scales
      (VAS) for competence and case difficulty were also used. During laparoscopic
      cholecystectomy, 21 participants were evaluated by the attending surgeon, by 2
      trained observers and by self-assessment while dissecting the gallbladder from
      the liver bed. RESULTS: The intraclass correlation coefficient (ICC) for the
      total GOALS score was .89 (95% confidence interval [CI] .74 to .95) between
      observers, .82 (95% CI .67 to .92) between observers and attending surgeons, and
      .70 (95% CI .37 to .87) between participants and attending surgeons. The ICCs
      (observers) for the VAS (competence) and the checklist were .69 and .70,
      respectively. The mean total GOALS score (observers) for novices (postgraduate
      years [PGYs] 1 through 3) was 13 (95% CI 10.3 to 15.7) compared with 19.4 (95% CI
      17.2 to 21.5) for experienced (PGY 4 through attending surgeons, P = .0006). The
      VAS demonstrated a difference in scores between novice and experienced
      participants (P = .001); however, the task checklist did not (P = .09).
      CONCLUSIONS: These data indicate that GOALS is feasible, reliable, and valid.
      They also suggest that it is superior to the task checklist and VAS for
      evaluation of technical skill by experienced raters. The findings support the use
      of GOALS in the training and evaluation of laparoscopic skills.

PMID- 15972182
TI  - Anatomic left hepatic trisegmentectomy.
AB  - The technique of left trisegmentectomy was first published in 1982 and consists
      in the removal of the left liver (segments II, III, and IV) along with the right
      anterior sector (segments V and VIII). This procedure is based on the knowledge
      of the segmental liver anatomy. There are only a few technical reports describing
      this complex procedure. We describe an anatomic and standardized way to identify
      and isolate the glissonian sheaths of the left liver segments along with the
      portal pedicles from right anterior sector (segments V and VIII). The middle and
      left hepatic veins are dissected using Arantius ligament as landmark. With this
      technique, it is possible to achieve inflow and outflow control of the involved
      liver segments without hilar dissection or clamping. This technique provides a
      safe way to perform a left extended hepatectomy without warm ischemia of the
      relatively small remnant liver.

PMID- 15972183
TI  - A new open anterior tension-free onlay patch technique for inguinofemoral hernia
      repair.
AB  - BACKGROUND: The high rate of misdiagnosed, coincident, or recurrent femoral
      hernias while or after mesh herniorrhaphy suggests its systematic search. We
      introduced a new open anterior tension-free mesh herniorrhaphy with a novel
      design. METHODS: A description of the operative technique and patients
      demographics is presented. RESULTS: Two hundred sixty-eight hernias were repaired
      with this technique in a 5-year period. Two hundred twelve patients had a primary
      inguinal hernia. An unsuspected femoral hernia was discovered in 39 patients with
      a preoperatively diagnosed inguinal hernia. Operative time was 45 minutes, most
      patients were discharged in less than 24 hours, no recurrence has been noted, and
      minor complications were present. Most patients had minimal pain and returned to
      their normal activities within 10 days after surgery. CONCLUSION: This technique
      has the same advantages of open tension-free repairs, allows identification of
      femoral hernias, and protects a herniorrhaphy for recurrence.

PMID- 15972184
TI  - The application of dermatotraction for primary skin closure.
AB  - Management of an open wound is a problem frequently encountered in the treatment
      of fractures. Skin grafting, rotational flaps, free flaps, and healing by
      secondary intention add a considerable amount of morbidity and cost to the
      patient. Therefore, it is ideal to obtain primary closure when possible. This
      communication describes a technique that uses spinal needles, using towel clips
      and the natural stretching ability of the skin to enable primary closure of
      wounds. The technique described uses dermatotraction to stretch the skin is a
      cost-effective way to achieve primary closure of large wounds with supplies that
      are readily available in every operating room.

PMID- 15972185
TI  - Stapled hemorrhoidectomy.
AB  - Stapled hemorrhoidectomy has rapidly evolved and become the procedure of choice
      for primarily internal hemorrhoids. Even though the technique is relatively
      straightforward, only strict adherence to its principles will avoid serious
      complications and preserve the previously described benefits of this method.
      Recurring questions during teaching courses as well as several pitfalls that
      might result in suboptimal outcomes have prompted us to highlight some important
      details and modifications of the surgical technique.

PMID- 15972186
TI  - Quantification of motion characteristics and forces applied to tissues during
      suturing.
AB  - BACKGROUND: The quantification of movement processes describes how a movement is
      generated. These process measures have been shown to be effective sources of
      feedback to facilitate motor learning and can thus be applied to teach
      fundamental technical skills in surgery. The aim of this study was to determine,
      through detailed analyses, whether specific process measures of hand motions and
      forces imposed on tissues during suturing were sensitive to (1) practice and (2)
      levels of surgical expertise. METHODS: Six junior surgical residents (PGY-1) and
      7 faculty surgeons were required to perform 20 simulated sutures on an artificial
      artery model, during which time the performers' hand movements were tracked by
      electromagnetic markers and the quantity of force they applied was measured by a
      force platform holding the arterial suturing models. The amount of wrist rotation
      and peak hand velocity produced during the suturing movement, peak and average
      forces applied to the tissue, the temporal difference between force and wrist
      rotation onsets, and the total suturing time were evaluated. RESULTS: Surgeons
      showed greater wrist rotation, higher average forces, shorter force-rotation
      initiation times, and shorter suturing times than did junior residents. Only the
      amount of wrist rotation and the time elapsed between force and wrist rotation
      onsets improved with practice for the junior group. CONCLUSIONS: Although all 4
      variables measured can be used to distinguish between expert and novice
      performances, only the process measures (wrist rotation and force-rotation
      initiation time) changed as a result of practice for the junior residents. Thus,
      these measures can be used to facilitate skills learning by serving as a source
      of detailed structured feedback to trainees.

PMID- 15972187
TI  - Implementation of a Web- and simulation-based curriculum to ease the transition
      from medical school to surgical internship.
AB  - BACKGROUND: Starting a surgical internship is a stressful experience. We
      developed a web and simulation-based curriculum to ease this transition. METHODS:
      We created an educational website containing a curriculum of commonly encountered
      on call situations. After match day in 2003, we contacted all of our new surgical
      interns. We performed a confidence assessment using a Likert-scale questionnaire,
      and the trainees were given access to the curriculum. In June 2003, we performed
      human patient simulator sessions. The participants were asked to provide feedback
      regarding the simulator experience. During the first week of residency, they were
      again asked to answer the confidence questionnaire. RESULTS: Sixteen residents
      (94%) used the web curriculum, and 17 (100%) participated in the simulations.
      Eleven (65%) filled out both questionnaires. The confidence score improved from
      5.4 to 6.7 (P < .0001). CONCLUSIONS: A web and simulation-based curriculum for
      incoming house staff is feasible. Studies are underway to validate this novel
      method and to expand its use for surgical education.

PMID- 15972188
TI  - Why are women deterred from general surgery training?
AB  - BACKGROUND: This study explored the factors contributing to the low application
      rates to general surgery (GS) residency by female students and compared
      perceptions of GS between students and female surgeons. METHODS: We distributed
      surveys to final-year students at 4 medical schools and nationwide to every
      female general surgeon in Canada. RESULTS: Of students who were deterred from GS,
      women were less likely than men to meet a same-sex GS role model and more likely
      to experience gender-based discrimination during their GS rotation (P < .05).
      Female students had the perception that GS was incompatible with a rewarding
      family life, happy marriage, or having children, whereas female surgeons were far
      more positive about their career choice. CONCLUSIONS: Both real and perceived
      barriers may deter women from a career in GS. Real barriers include sex-based
      discrimination and a lack of female role models in GS. There are also clear
      differences in perception between students and surgeons regarding family and
      lifestyle in GS that must be addressed.

PMID- 15972189
TI  - The effect of a rotating night-float coverage scheme on preventable and
      potentially preventable morbidity at a level 1 trauma center.
AB  - BACKGROUND: The effect of resident work-hour restriction on patient outcome
      remains controversial. METHODS: Demographic data, mechanism of injury, length of
      hospital stay length of intensive care unit (ICU) stay, ventilator days,
      mortality, and complication data were prospectively collected for 11 months
      before and 11 months after institution of a rotating night-float system. Seven
      attending surgeons reviewed all complications and categorized each as
      preventable, potentially preventable, or nonpreventable. RESULTS: Both study
      periods were comparable with respect to demographic data, mean Injury Severity
      Score, mechanism of injury, and admissions. Limitation of resident work hours had
      no effect on length of hospital or ICU stay, ventilator days, or mortality. Work
      hour restrictions did not increase or decrease the total number of complications
      nor did it alter the distribution of those determined to be preventable or
      potentially preventable. CONCLUSIONS: Resident work-hour restrictions were not
      associated with significant improvement or deterioration in patient outcome.

PMID- 15972190
TI  - Laryngeal involvement by differentiated thyroid carcinoma.
AB  - BACKGROUND: Invasion of the larynx by differentiated thyroid gland carcinoma is
      uncommon but causes serious morbidity and mortality when present. METHODS: The
      clinicopathologic characteristics of 5 patients in which a total laryngectomy had
      to be performed for differentiated thyroid carcinoma are analyzed. Special
      reference is paid to the histologic intralaryngeal tumor spread, which is
      evaluated on whole-organ section. RESULTS: All patients presented with hoarseness
      and/or dyspnea. Two patients are alive at 44 and 115 months. One patient died of
      intercurrent disease 2 months and 2 patients with disease 6 and 14 months after
      surgery. In all cases, intralaryngeal tumor spread was observed. Invasion of the
      larynx occurs by direct extension or by posterior tumor growth around the edge of
      the thyroid cartilage. CONCLUSION: In rare cases, differentiated thyroid
      carcinoma can widely infiltrate the larynx, making total laryngectomy
      unavoidable. The diagnosis of intralaryngeal tumor spread is done by imaging and
      endoscopy.

PMID- 15972191
TI  - Role of first rib stump length in recurrent neurogenic thoracic outlet syndrome.

PMID- 15972194
TI  - Improvement of tissue harmonic imaging using the pulse-inversion technique.
AB  - Harmonic imaging has brought about significant improvements in image quality by
      taking advantage of the second harmonic component, but it still has one
      shortcoming, namely, a low signal-to-noise ratio. In this paper, a pulse
      inversion technique is used in second harmonic imaging for biologic tissues to
      increase the signal-to-noise ratio. Enhancement of the second harmonic component
      is theoretically analyzed based on the theory of the finite amplitude sound wave
      and confirmed by the measurement. Second harmonic imaging for biologic tissues is
      constructed with the pulse-inversion technique and compared with the traditional
      fundamental frequency and also with second harmonic imaging before the use of
      this technique. Results demonstrate that this technique yields a dramatically
      cleaner and sharper contrast between the different structures of biologic tissues
      in ultrasonic images.

PMID- 15972193
TI  - The efficacy assessment of thigh volume in predicting intrauterine fetal growth
      restriction by three-dimensional ultrasound.
AB  - Intrauterine growth restriction (IUGR) is an important issue in perinatology. To
      assess the efficacy of fetal thigh volume (ThVol) in predicting IUGR, we
      undertook a prospective cross-sectional study using quantitative 3-D ultrasound
      (US). During the study period, 30 fetuses with IUGR and 282 fetuses with non-IUGR
      were included for the ThVol assessment in utero by 3-D US. All the fetuses were
      singletons and had follow-up to the delivery to determine whether they were
      complicated with IUGR or not. Our results showed fetal ThVol assessed by 3-D US
      can differentiate fetuses with IUGR from fetuses with non-IUGR well. Using the
      10th percentile as the screening threshold, the sensitivity of fetal ThVol in
      predicting IUGR was 86.6%, with specificity 91.1%, predictive value of positive
      test 51.0%, predictive value of negative test 98.5% and accuracy 90.7%. In
      conclusion, fetal ThVol assessed by quantitative 3-D US can be used to predict
      fetuses with IUGR antenatally. We believe fetal ThVol assessment by 3-D US would
      be a useful test in detecting fetuses with IUGR.

PMID- 15972195
TI  - Normal reference intervals and ranges of side-to-side and day-to-day variability
      of ocular blood flow Doppler parameters.
AB  - The study presents normal reference intervals and ranges of "normal" side-to-side
      and day-to-day variability of ocular blood flow Doppler parameters. Peak-systolic
      (PSV), end-diastolic velocity (EDV) and impedance indices in the ophthalmic
      artery (OA), the central retinal artery (CRA) and the short posterior ciliary
      artery (SPCA) of both orbits were determined with color-coded duplex sonography
      in 140 healthy volunteers (range 18 to 83 y; 68 men and 72 women). Decreases in
      flow velocities and concomitant increases in impedance indices were found in all
      arteries with advancing age. The PSV and the EDV values for the OA, the CRA and
      the SPCA in the age group less than 40 yr-old were 40.6 +/- 8.9 and 11.2 +/- 3.7,
      9.9 +/- 1.8 and 3.7 +/- 0.9, 13.8 +/- 2.6 and 5.7 +/- 1.5 cm/s (mean +/- SD),
      respectively. In the 40 to 60 yr-old age group, the values were 35 +/- 7.9 and
      10.7 +/- 4.3, 9.7 +/- 2 and 3.5 +/- 0.8, 13.5 +/- 2.9 and 5.3 +/- 1.5 cm/s. In
      the age group over 60 yr-old, the values were 34 +/- 8 and 8.4 +/- 3.3, 9.3 +/- 2
      and 3 +/- 0.9, 12.8 +/- 2.4 and 4.3 +/- 1.2 cm/s. In the youngest age group, the
      EDV in the CRA and the SPCA was higher in women, while in the OA the PSV and the
      EDV were higher in men. Ranges of side-to-side variability in the OA, the CRA and
      the SPCA, determined with repeatability coefficient for the PSV and the EDV, were
      24, 5.4, 7.5 cm/s and 11, 2.5, 4.2 cm/s, respectively, whereas the values for day
      to-day variability were 16.8, 4.3, 6.7 cm/s and 5.6, 1.7 and 3.9 cm/s. Ocular
      blood flow Doppler parameters range widely and are significantly age and sex
      dependent. Ranges of "normal" side-to-side and day-to-day variability of the
      parameters can help to determine abnormal flow pattern.

PMID- 15972196
TI  - Automated quantitative volumetric breast ultrasound data-acquisition system.
AB  - This paper describes the development and initial testing of an automated
      ultrasound imaging technique to acquire quantitative volumetric breast data; the
      clinical application being breast cancer diagnosis and management. A novel
      mechanical scanner has been designed and constructed to constrain the breast
      tissue without compromising the image, to acquire images of the majority of the
      breast using a conventional B-mode scanner and to maintain patient comfort. An
      algorithm to improve upon simple depth-dependent amplification by compensating
      for tissue-dependent attenuation is applied to the images, making the grey-scale
      values represent local scattering properties more closely. Registration
      techniques have been developed to correct for geometric errors arising in the
      data set because of tissue movement and variations in speed of sound in the
      tissues. The data sets are reconstructed into volumes and viewed interactively. A
      pilot study of seven patients was performed and selected results are presented to
      illustrate lesion features. The automated scan reduces operator-dependence,
      provides clear information on the 3-D tissue boundaries and provides a full
      record for monitoring or surgical planning.

PMID- 15972197
TI  - Temporal calibration of freehand three-dimensional ultrasound using image
      alignment.
AB  - All freehand 3-D ultrasound systems have some latency between the acquisition of
      an image and its associated position. Previously, estimation of latency has been
      made by tracking a phantom in a sequence of images and correlating its motion to
      that recorded by the position sensor. However, tracking-based temporal
      calibration uses the assumption that latency is constant between scans. This
      paper presents a new method for temporal calibration that avoids this assumption.
      Temporal calibration is performed on the scan data by finding the latency at
      which the best alignment of the 2-D images within the reconstructed volume
      occurs. The mean voxel intensity variance is used as a global measure of the
      quality of alignment within the volume and is minimized with respect to latency
      for each scan. The new method is compared with previous methods using an
      ultrasound phantom. Finally, integration of temporal calibration with existing
      spatial calibration methods is discussed.

PMID- 15972198
TI  - Automated fetal head detection and measurement in ultrasound images by iterative
      randomized Hough transform.
AB  - An image-processing and object-detection method was developed to automate the
      measurements of biparietal diameter (BPD) and head circumference (HC) in
      ultrasound fetal images. The heads in 214 of 217 images were detected by an
      iterative randomized Hough transform. A head was assumed to have an elliptical
      shape with parameters progressively estimated by the iterative randomized Hough
      transform. No user input or size range of the head was required. The detection
      and measurement took 1.6 s on a personal computer. The interrun variations of the
      algorithm were small at 0.84% for BPD and 2.08% for HC. The differences between
      the automatic measurements and sonographers' manual measurements were 0.12% for
      BPD and -0.52% for HC. The 95% limits of agreement were -3.34%, 3.58% for BPD and
      -5.50%, 4.45% for HC. The results demonstrated that the automatic measurements
      were consistent and accurate. This method provides a valuable tool for fetal
      examinations.

PMID- 15972199
TI  - Clinical validation of common carotid artery wall distension assessment based on
      multigate Doppler processing.
AB  - Mechanical properties of human large arteries result from the interaction between
      blood pressure, wall distensibility and shear stress. Both the arterial diameter
      changes through the cardiac cycle (distension) and blood flow velocities can be
      noninvasively investigated through Doppler ultrasound approaches. Recently, an
      integrated system processing in real-time all the echo signals produced along an
      M-line has been developed. This system has been so far demonstrated to be
      suitable for accurate hemodynamic studies through the detection of blood velocity
      profiles. This paper reports on the extension of its processing capabilities to
      the real-time measurement of arterial distension. Tissue motion estimation is
      based on a modified 2-D autocorrelation algorithm. A novel adaptive approach to
      track wall position over time using the sum of the high-pass filtered
      displacement waveform and the low-pass filtered wall position is described. By
      observing the blood velocity profile, a rapid and accurate positioning of the
      ultrasound probe and an inherent check on perpendicular observation are provided.
      First clinical results obtained by measuring the distension of common carotid
      arteries in a group of 41 volunteers are reported and measurements are validated
      against those provided by a dedicated wall-track reference system. Average
      measured distension and diameter were 499 +/- 188 microm and 6.90 +/- 0.66 mm and
      intraobserver intrasession reproducibility tests showed coefficients of
      variability of 8.5% and 5.9%, respectively. The agreement between the proposed
      system and the reference system, expressed as bias +/- 2 SD of the differences,
      was -34 +/- 141 microm for distension and 0.05 +/- 1.07 mm for diameter.

PMID- 15972200
TI  - Hyperecho in ultrasound images of HIFU therapy: involvement of cavitation.
AB  - High-intensity focused ultrasound (US), or HIFU, treatment of soft tissues has
      been shown to result in a hyperechoic region in B-mode US images. We report on
      detecting cavitation in vivo in correlation with the appearance of a hyperechoic
      region. The US system consisted of a HIFU transducer (3.3 MHz), a broadband A
      mode transducer for active and passive cavitation detection and an US-imaging
      probe that were all confocal and synchronized. HIFU, at in situ intensities of
      220 to 1710 W/cm(2), was applied for 10 s to pig muscles in vivo. Active and
      passive cavitation detection results showed a strong correlation between the
      onset of cavitation and the appearance of a hyperechoic region. Passive
      cavitation detection results showed that inertial cavitation typically occurred
      prior (within 0.5 s) to the appearance of a hyperechoic region. The observed
      cavitation activity confirms that bubbles are present during the formation of a
      hyperechoic region at the HIFU focus.

PMID- 15972201
TI  - Investigation of the effect of subcutaneous fat on image quality performance of
      2D conventional imaging and tissue harmonic imaging.
AB  - Tissue harmonic imaging (THI) has been reported to improve contrast resolution,
      tissue differentiation and overall image quality in clinical examinations.
      However, a study carried out previously by the authors (Brown et al. 2004) found
      improvements only in spatial resolution and not in contrast resolution or
      anechoic target detection. This result may have been due to the homogeneity of
      the phantom. Biologic tissues are generally inhomogeneous and THI has been
      reported to improve image quality in the presence of large amounts of
      subcutaneous fat. The aims of the study were to simulate the distortion caused by
      subcutaneous fat to image quality and thus investigate further the improvements
      reported in anechoic target detection and contrast resolution performance with
      THI compared with 2D conventional imaging. In addition, the effect of three
      different types of fat-mimicking layer on image quality was examined. The
      abdominal transducer of two ultrasound scanners with 2D conventional imaging and
      THI were tested, the 4C1 (Aspen-Acuson, Siemens Co., CA, USA) and the C5-2 (ATL
      HDI 5000, ATL/Philips, Amsterdam, The Netherlands). An ex vivo subcutaneous pig
      fat layer was used to replicate beam distortion and phase aberration seen
      clinically in the presence of subcutaneous fat. Three different types of fat
      mimicking layers (olive oil, lard and lard with fish oil capsules) were
      evaluated. The subcutaneous pig fat layer demonstrated an improvement in anechoic
      target detection with THI compared with 2D conventional imaging, but no
      improvement was demonstrated in contrast resolution performance; a similar result
      was found in a previous study conducted by this research group (Brown et al.
      2004) while using this tissue-mimicking phantom without a fat layer. Similarly,
      while using the layers of olive oil, lard and lard with fish oil capsules,
      improvements due to THI were found in anechoic target detection but, again, no
      improvements were found for contrast resolution for any of the layer
      combinations. Therefore, it was felt that the lack of improvement in contrast
      resolution performance may be due to the test phantom design and not to whether a
      layer was present that caused beam distortion and phase aberrations.

PMID- 15972202
TI  - MRI-guided ultrasonic heating allows spatial control of exogenous luciferase in
      canine prostate.
AB  - The need for efficient and controlled delivery is one of the major obstacles to
      clinical use of gene therapy. In this study, we investigated the use of magnetic
      resonance imaging-monitored ultrasound (US) to induce expression of luciferase
      after local injection of the construct Ad-HSP-Luc, an adenoviral vector
      containing a transgene encoding firefly luciferase under the control of the human
      hsp70B promoter. The hsp promoter allows induction of the associated transgene
      only in areas that are subsequently heated after infection. US imaging was used
      to guide the injection of purified virus into both lobes of the prostates of
      three beagles. At 48 h after injection, the left lobe of the prostate was heated
      using a 1.5-MHz US transducer driven by a multichannel radiofrequency system and
      employing an magnetic resonance imaging guidance system. High levels of
      luciferase expression were observed only in areas exposed to ultrasonic heating.
      This study demonstrates the feasibility of using ultrasonic heating to control
      transgene expression spatially using a minimally-invasive approach.

PMID- 15972203
TI  - Glucose measurements with sensors and ultrasound.
AB  - Accurate monitoring of the blood glucose level in diabetics is essential in
      preventing complications. Generally, conventional over-the-counter glucose meters
      require frequent painful finger punctures to obtain samples, which makes a
      noninvasive method preferable. The purpose of this study was to demonstrate that
      glucose levels can be measured transdermally with the combination of the low
      profile cymbal array and an electrochemical glucose sensor consisting of
      amperometric electrodes and a novel glucose oxidase hydrogel. Interstitial fluid
      glucose concentrations can be determined with the electrochemical glucose sensor
      after the skin is made permeable to glucose by ultrasound (US) (20 kHz) with the
      thin (< 7 mm) and light (< 22 g) cymbal array. Using this array to deliver
      insulin into hyperglycemic rats, our previous experiments demonstrated that blood
      glucose levels would decrease 233.3 mg/dl with 5 min of US exposure. With the
      sensor and array, our goal was to determine the glucose levels of hyperglycemic
      rats noninvasively and evaluate the possible bioeffects. A total of 12
      anesthetized rats were placed into two groups (US exposure group and control
      group) and the array (I(SPTP) = 100 mW/cm(2)) with a saline reservoir operating
      for 20 min was affixed to the abdomen. The array was removed and an
      electrochemical glucose sensor was placed on the exposed area to determine the
      glucose concentrations through the skin. Comparison was made using a commercial
      glucose meter with the blood collected from a jugular vein. The average blood
      glucose level determined by the sensor was 356.0 +/- 116.6 mg/dl, and the glucose
      level measured by the commercial glucose meter was 424.8 +/- 59.1 mg/dl. These
      results supported the use of this novel system consisting of the electrochemical
      glucose sensor and the cymbal array for glucose monitoring.

PMID- 15972204
TI  - Effectiveness of lipid microbubbles and ultrasound in declotting thrombosis.
AB  - The objectives of this study were to determine the effectiveness of lipid
      encapsulated microbubbles and ultrasound (US) in recanalizing arteriovenous graft
      thrombi and the effect that tissue attenuation has on the success rate. A total
      of 55 thrombotic occlusions were created in four canines. The thrombosed grafts
      were randomly treated with two different 1-MHz US intensities, low (0.4 to 0.6
      W/cm(2)) and high (10 W/cm(2)). Intragraft microbubbles were compared with
      intragraft saline and with the same dose of microbubbles given IV. IV
      microbubbles were also given both in the presence and absence of a tissue
      mimicking phantom. High-intensity US (10 W/cm(2)) with intragraft microbubbles
      produced significantly higher patency and flow scores than did US with saline (p
      < 0.01). US with IV microbubbles had higher success rates in recanalizing
      thrombosed grafts than did US alone at all intensities. Attenuation reduced the
      rate at which successful recanalization occurred at both low and high
      intensities. US and microbubbles are capable of recanalizing acute arteriovenous
      graft thromboses. Higher intensities may be needed in the presence of tissue
      attenuation.

PMID- 15972205
TI  - In vitro speed of sound measurement at intact human femur specimens.
AB  - Quantitative ultrasound has been recognized as a useful tool for fracture risk
      prediction. Current measurement techniques are limited to peripheral skeletal
      sites. Our objective was to demonstrate the in vitro feasibility of ultrasonic
      velocity measurements on human proximal femur and to investigate the relationship
      between velocity and bone mineral density (BMD). Sound velocity images were
      computed from 2-D scans performed on 38 excised human femurs in transmission at
      0.5 MHz. Different regions-of-interest were investigated. Dual x-ray
      absorptiometry scans have been achieved for BMD measurements in site-matched
      regions. Our study demonstrates the feasibility of ultrasonic velocity
      measurements at the hip with reasonable precision (coefficient of variation of
      0.3%). The best prediction of BMD was reached in the intertrochanter region (r(2)
      = 0.91, p < 10(-4)), with a residual error of 0.06 g/cm(2) (10%). Because BMD
      measured at the femur is the best predictor of hip fracture risk, the highly
      significant correlation and small residual error found in this study suggest that
      speed of sound measurement at the femur might be a good candidate for hip
      fracture risk prediction.

PMID- 15972206
TI  - Social anxiety and posttraumatic stress in combat veterans: relations to well
      being and character strengths.
AB  - There are few studies examining the relationship between psychopathology and
      positive experiences and traits. Although initial studies suggest persons with
      posttraumatic stress disorder (PTSD) are at increased risk for excessive social
      anxiety, there have been no studies to date evaluating how these conditions might
      interact to affect positive experiences and traits. Using self-report scales,
      informant ratings, and experience-sampling methodologies, we examined the
      association of social anxiety with well-being and character strengths in veterans
      with and without PTSD. Controlling for PTSD and trait negative affect, social
      anxiety was negatively related to global ratings of well-being and character
      strengths. Social anxiety also accounted for incremental variance in day-to-day
      well-being (i.e., daily affect balance, percentage of pleasant days, positive
      social activity, self-esteem, gratitude) over a 14-day assessment period.
      Although veterans with PTSD reported lower levels of global and daily well-being
      and character strengths than veterans without PTSD, a diagnosis of PTSD failed to
      exhibit unique relationships with these constructs. Building on a growing body of
      work, these data suggest that social anxiety is uniquely associated with
      disturbances in positive experiences, events, and traits. Our findings support
      the value of directly addressing social anxiety in the study and treatment of
      PTSD.

PMID- 15972207
TI  - Diagnostic potential of phosphorylated cardiac troponin I as a sensitive, cardiac
      specific marker for early acute coronary syndrome: preliminary report.
AB  - BACKGROUND: Cardiac troponin I (cTnI) has low sensitivity in the early hours of
      acute coronary syndrome (ACS). For patients with early ACS symptoms, we
      determined the diagnostic potential of an immunoassay for phosphorylated cTnI
      (PO(4)-cTnI). METHODS: In a prospective study of 61 emergency department patients
      with suspected ACS, we compared a novel plasma immunoassay for PO(4)-cTnI to cTnI
      overall and in a subgroup with symptoms < or =4 h duration (n = 31). Admission
      PO(4)-cTnI and cTnI assays (thresholds determined by ROC curve) were analyzed in
      a blinded fashion against the clinical, ECG and coronary angiographic diagnosis
      of ACS. RESULTS: Overall, PO(4)-cTnI sensitivity was significantly higher than
      cTnI (82% vs. 50%, respectively, P < 0.05) and PO(4)-cTnI specificity was 81% (n
      = 61). Addition of PO(4)-cTnI to cTnI improved sensitivity to 91% vs. 50% for
      cTnI alone (P < 0.001). In the < or =4 h subgroup (n = 31), PO(4)-cTnI
      sensitivity was significantly higher than cTnI (79% vs. 26%, respectively, P <
      0.01) and PO(4)-cTnI specificity was 75%. In the same < or =4 h subgroup,
      addition of PO(4)-cTnI to cTnI improved sensitivity to 84% vs. 26% for cTnI alone
      (P = 0.001). CONCLUSIONS: The results suggest that PO(4)-cTnI, alone or in
      combination with cTnI, warrants further investigation as a sensitive, cardiac
      specific diagnostic tool for early ACS.

PMID- 15972208
TI  - Incorrect glucose results in off-meter sample application with reflectance
      meters: a case report.

PMID- 15972209
TI  - The effects of cocaine on CART expression in the rat nucleus accumbens: a
      possible role for corticosterone.
AB  - CART (Cocaine- and Amphetamine-Regulated Transcript) was initially described as
      an mRNA which had increased expression in the rat striatum following
      administration of acute cocaine or amphetamine but not saline. However, not all
      subsequent studies confirmed this. The present study aimed to repeat experiments
      with conflicting results and to reexamine and extend the original finding of
      acute regulation of nucleus accumbens CART mRNA by cocaine. Acute administration
      of cocaine failed to produce any change in levels of CART mRNA or peptide.
      Chronic administration of cocaine, as well as unilateral 6-hydroxydopamine
      lesions, also failed to alter CART mRNA levels in the accumbens. However, binge
      administration of cocaine, which also caused some seizures, did cause a
      significant increase in CART message. Given the involvement of corticosteroids
      with both stress and the effects of psychostimulants, we examined the possible
      effects of corticosteroids. We acutely administered ascending doses of
      corticosterone and found an increase in CART message. Similar effects were seen
      on CART peptides after acute corticosterone administration, and acute metyrapone
      administration was found to reduce CART peptide levels in the accumbens. This
      suggests that CART mRNA may be regulated by cocaine under certain conditions,
      such as binge administration, and this may at least partly involve
      corticosterone.

PMID- 15972210
TI  - Omeprazole-induced slowing of gastrointestinal transit in mice can be countered
      with tegaserod.
AB  - Omeprazole, besides suppressing gastric acid, causes delayed gastric emptying,
      which may be associated with aggravated dyspeptic symptoms. Effects of omeprazole
      on small intestinal transit are unknown. In this study, we evaluated in mice if
      (a) omeprazole affects transit of a meal through the stomach and small intestine
      and (b) co-treatment with the promotility agent, tegaserod, can prevent the
      slowing effect of omeprazole. Omeprazole (40-150 mg/kg, i.p. once daily for 5
      days) delayed gastric emptying of the meal in a dose-related manner. Small
      intestinal transit was then evaluated at the lowest dose of omeprazole (40 mg/kg)
      that did not retard gastric emptying. Such transit was significantly delayed
      after this dose of omeprazole compared with vehicle-treated controls. When
      tegaserod (0.10 mg/kg) was administered concomitantly with the omeprazole, small
      intestinal transit of the meal was not slowed and was not different from
      controls. These results show that omeprazole reduces aboral transit of luminal
      contents through the stomach and small bowel of mice and that this delay is
      reversed by tegaserod.

PMID- 15972211
TI  - The professional self-image of nurses in Belgian hospitals: a cross-sectional
      questionnaire survey.
AB  - This paper reports data on the professional self-image of 9638 nurses employed in
      22 Belgian general hospitals with the goal of identifying problems affecting
      recruitment and retention. Nurses reported having a positive self-image. Most
      were proud to be a nurse and considered themselves competent health professionals
      having great responsibility. Although they reported that an ideal practice
      requires effective teamwork, supportive management, societal recognition, and
      sufficient time to perform their duties, they also felt that these essential
      conditions were absent in daily practice.

PMID- 15972212
TI  - Comparison of biophysical stimuli for mechano-regulation of tissue
      differentiation during fracture healing.
AB  - Most long-bone fractures heal through indirect or secondary fracture healing, a
      complex process in which endochondral ossification is an essential part and bone
      is regenerated by tissue differentiation. This process is sensitive to the
      mechanical environment, and several authors have proposed mechano-regulation
      algorithms to describe it using strain, pore pressure and/or interstitial fluid
      velocity as biofeedback variables. The aim of this study was to compare various
      mechano-regulation algorithms' abilities to describe normal fracture healing in
      one computational model. Additionally, we hypothesized that tissue
      differentiation during normal fracture healing could be equally well regulated by
      the individual mechanical stimuli, e.g. deviatoric strain, pore pressure or fluid
      velocity. A biphasic finite element model of an ovine tibia with a 3mm fracture
      gap and callus was used to simulate the course of tissue differentiation during
      normal fracture healing. The load applied was regulated in a biofeedback loop,
      where the load magnitude was determined by the interfragmentary movement in the
      fracture gap. All the previously published mechano-regulation algorithms studied,
      simulated the course of normal fracture healing correctly. They predicted (1)
      intramembranous bone formation along the periosteum and callus tip, (2)
      endochondral ossification within the external callus and cortical gap, and (3)
      creeping substitution of bone towards the gap from the initial lateral osseous
      bridge. Some differences between the effects of the algorithms were seen, but
      they were not significant. None of the volumetric components, i.e. pore pressure
      or fluid velocity, alone were able to correctly predict spatial or temporal
      tissue distribution during fracture healing. However, simulation as a function of
      only deviatoric strain accurately predicted the course of normal fracture
      healing. This suggests that the deviatoric component may be the most significant
      mechanical parameter to guide tissue differentiation during indirect fracture
      healing.

PMID- 15972213
TI  - Rectus femoris and vastus intermedius fiber excursions predicted by three
      dimensional muscle models.
AB  - Computer models of the musculoskeletal system frequently represent the force
      length behavior of muscle with a lumped-parameter model. Lumped-parameter models
      use simple geometric shapes to characterize the arrangement of muscle fibers and
      tendon; this may inaccurately represent changes in fiber length and the resulting
      force-length behavior, especially for muscles with complex architecture. The
      purpose of this study was to determine the extent to which the complex features
      of the rectus femoris and vastus intermedius architectures affect the fiber
      changes in length ("fiber excursions"). We created three-dimensional finite
      element models of the rectus femoris and vastus intermedius muscles based on
      magnetic resonance (MR) images, and compared the fiber excursions predicted by
      the finite-element models with fiber excursions predicted by lumped-parameter
      models of these muscles. The finite-element models predicted rectus femoris fiber
      excursions (over a 100 degrees range of knee flexion) that varied from 55% to 70%
      of the excursion of the muscle-tendon unit and vastus intermedius fiber
      excursions that varied from 55% to 98% of the excursion muscle-tendon unit. In
      contrast, the lumped-parameter model of the rectus femoris predicted fiber
      excursions that were 86% of the excursion of the muscle-tendon unit and vastus
      intermedius fiber excursions that were 97% of the excursion of the muscle-tendon
      unit. These results suggest that fiber excursions of many fibers are
      overestimated in lumped-parameter models of these muscles. These new
      representations of muscle architecture can improve the accuracy of computer
      simulations of movement and provide insight into muscle design.

PMID- 15972214
TI  - A mechanism for balancing the human body on the hips.
AB  - A mechanism for the postural balance of the human torso over the hip joints is
      reported that does not appear to have been fully recognised. The centre of
      gravity of the torso is usually considered poised above the hips. This is in a
      state of unstable equilibrium. Here, we propose that body weight acting through
      the sacrum is counter-balanced by tension in the ilio-femoral ligament; the hips
      acting as the fulcrum. This places the torso in stable equilibrium and means that
      balance may be maintained with minimal muscular forces. The joint reaction force
      due to this mechanism in a two-legged stance is then of the order of the body
      weight on each hip. An implication is that capsular ligaments are important and
      consideration should be given to retaining or restoring them as much as possible
      in hip arthroplasty.

PMID- 15972215
TI  - Muscle fibre length-to-moment arm ratios in the human lower limb determined in
      vivo.
AB  - The purpose of this study was to quantify in vivo the fibre length (L)-to-moment
      arm (d) ratio (L/d) in the major ankle plantarflexors and knee extensors of 21
      healthy men. Measurements of L were taken in the gastrocnemius medialis,
      gastrocnemius lateralis, soleus, vastus lateralis and vastus intermedius muscles
      using ultrasound scanning. Measurements of d were taken in the Achilles tendon
      (d(AT)) and patellar tendon (d(PT)) using magnetic resonance imaging. The
      relations between (a) L in each ankle plantarflexor muscle and d(AT), (b) L in
      each knee extensor muscle and d(PT), and (c) d(AT) and d(PT,) were analyzed with
      Pearson correlation coefficients. There was no significant relation (P>0.05)
      between any of the above parameters, with the correlation coefficient values
      ranging from -0.2 to 0.29. These results contradict previous findings that L
      scales with d, indicating that skeletal size differences between individuals may
      not always be associated with predictable differences in muscle architecture.
      This needs to be accounted for when information about the L/d ratio of a given
      muscle-joint in a given individual is required, as for example is the case when
      assessing the suitability of a potential donor muscle in surgical tendon
      transfer.

PMID- 15972216
TI  - The influence of substrate charge and molecular structure on interphase transfer
      in cloud point extraction systems.
AB  - The specificity of interphase transfer of organic reagents of different types
      between water and the nonionic-surfactant-rich phases at the cloud point
      temperature was investigated. In contrast to organic solvents, the ability of the
      micellar phases to extract highly charged ions of organic reagents was shown.
      Further evidence of the specificity of interphase transfer in micellar-extraction
      systems is independent and cooperative influence of substrate molecular structure
      and hydrophobicity on their distribution. The appearance of host-guest phenomenon
      in cloud point extraction systems that is inherent in organized systems with
      molecules of the receptors was established. The possibility of describing reagent
      distribution using regressions that consider substrate hydrophobicity and
      molecular structure in the cloud point extraction systems was shown.

PMID- 15972217
TI  - The activation of memory CD4(+) T cells and CD8(+) T cells in patients with
      multiple sclerosis.
AB  - To reevaluate whether an association exists between the clinical course of
      multiple sclerosis (MS) and the activation of memory T cells, we investigated the
      phenotype of T cells in peripheral blood and cerebrospinal fluid (CSF) of
      patients with MS using five-color flow cytometry. A cross-sectional study with 39
      relapsing-remitting MS patients demonstrated that the percentage of
      CD25(+)CD45RO(+)CD4(+)CD3(+) cells was significantly increased in peripheral
      blood as well as in CSF of active MS patients compared with inactive MS patients.
      A longitudinal study with 11 relapsing-remitting MS patients also showed a higher
      percentage of CD25(+)CD45RO(+)CD4(+)CD3(+) cells in peripheral blood at the phase
      of exacerbation than during remission. On the other hand, regardless of the
      disease activity, the percentage of CD25(+)CD45RO(+)CD8(+)CD3(+) cells in
      peripheral blood was significantly higher in patients with MS than in healthy
      control subjects. A lower percentage of CD25(+)CD45RO(+)CD8(+)CD3(+) cells in CSF
      was observed in active MS patients compared with inactive MS patients. These
      results suggest that the activation of memory CD4(+) T cells is associated with
      the exacerbation of MS and activation of memory CD8(+) T cells reflects systemic
      immunological dysregulation in MS patients. Transient as well as continuous
      activation of T cells by recall antigens may be involved in the disease course of
      MS.

PMID- 15972218
TI  - HTLV-1 proviral load in peripheral blood mononuclear cells quantified in 100
      HAM/TSP patients: a marker of disease progression.
AB  - A high proviral load of human T cell lymphotropic virus type 1 (HTLV-1) in
      peripheral blood mononuclear cells (PBMCs) has been reported in patients with
      HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of
      the present study was to investigate the role of HTLV-1 proviral load in PBMCs
      (expressed as the number of copies per 10(6) PBMCs) in HAM/TSP disease course.
      One hundred consecutive HAM/TSP patients were recruited and assigned on the basis
      of the disability score and disease duration to either a rapid (n=38) or a slow
      (n=62) progression group. Thirty-four asymptomatic HTLV-1 carriers were also
      included. HTLV-1 proviral load was quantified in all HAM/TSP patients and
      asymptomatic subjects. The mean HTLV-1 proviral load was 6-fold lower in
      asymptomatic carriers than in HAM/TSP patients (18,224+/-24,811 vs. 107,905+/
      96,651, p<0.0001) and significantly higher in rapid progression patients than in
      slow progression patients (146,469+/-98,943 vs. 84,270+/-87,912, p=0.0002). HTLV
      1 proviral load in HAM/TSP patients was independent of age at the time of study,
      age at onset, and disease duration, and was not related to ophthalmological
      associated disease or Chisholm grade. A high level of pulmonary lymphocytosis
      correlated with high HTLV-1 proviral load level (p=0.01). Our results suggest
      that the level of HTLV-1 proviral load in PBMCs parallels the course of HTLV-1
      infection, being low in asymptomatic carriers and high and very high,
      respectively, in slow and rapid progression HAM/TSP patients. The magnitude of
      the HTLV-1 proviral load in PBMCs can be used as a biological marker of disease
      progression and could be a useful marker of disease activity in the monitoring of
      therapeutic trials.

PMID- 15972219
TI  - Fluid in the flute: Reversible hydromyelia.
AB  - Non-communicating syrinx formation in association with demyelinating disease has
      been reported in approximately 50 patients. It has been unknown whether this is a
      permanent or potentially reversible phenomenon. We report a patient with acute
      transverse myelitis who developed a syrinx that resolved within 6 months.
      Mechanisms of syrinx formation in demyelinating disease are discussed.

PMID- 15972220
TI  - Unilateral retrobulbar optic neuritis due to varicella zoster virus in a patient
      with AIDS: a case report and review of the literature.
AB  - Unilateral retrobulbar optic neuritis developed in a 43-year-old man with
      acquired immune deficiency syndrome (AIDS). This was secondary to varicella
      zoster virus (VZV) as confirmed by cerebrospinal fluid (CSF) polymerase chain
      reaction (PCR) detection of VZV in the cerebrospinal fluid. There was no typical
      cutaneous infection and no evidence of retinitis. The onset of unexplained visual
      loss due to optic neuritis in HIV positive individuals may be due to VZV
      infection. Prompt recognition, and early intervention with antiVZV therapy may
      preserve vision. Retrobulbar optic neuritis secondary to VZV infection should be
      considered in immunocompromised patients even in the absence of cutaneous or
      retinal lesions. Previous cases are reviewed and the varied nature of viral
      transport in the nervous system is noted.

PMID- 15972221
TI  - Influence of cAMP on reporter bioassays for dioxin and dioxin-like compounds.
AB  - In reporter assays for detection of dioxins, the dioxin-responsive element (DRE)
      is generally used as a sensor sequence. In several systems, the CYP1A1 promoter
      containing DREs (DRE(cyp)) is inserted into a part of the long terminal repeat of
      mouse mammary tumor virus (LTR(MMTV)) to improve sensitivity of assays. We found
      that DRE(cyp)-LTR(MMTV) responds not only to dioxins and dioxin-like compounds
      but also to forskolin, a cAMP-elevating agent. This effect was dose-dependent and
      reproduced by other cAMP-elevating agents including 8-bromo-cAMP and 3-isobutyl
      methylxanthine. The cAMP response element (CRE) and CRE-like sequences were
      absent in DRE(cyp)-LTR(MMTV) and not involved in this process. In contrast to the
      effect of dioxin, the activation of DRE(cyp)-LTR(MMTV) by cAMP was independent of
      the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor for
      DRE. Furthermore, neither DRE(cyp), LTR(MMTV) nor the consensus sequence of DRE
      alone was activated in response to cAMP. These data elucidated for the first time
      that the combination of DRE(cyp) with LTR(MMTV) causes a peculiar response to
      cAMP and suggested that use of AhR antagonists is essential to exclude false
      positive responses of DRE(cyp)-LTR(MMTV)-based bioassays for detection and
      quantification of dioxins and dioxin-like compounds.

PMID- 15972222
TI  - Amino acid sequence of a basic aspartate-49-phospholipase A2 from Trimeresurus
      flavoviridis venom and phylogenetic analysis of Crotalinae venom phospholipases
      A2.
AB  - Trimeresurus flavoviridis snakes inhabit the southwestern islands of Japan: Amami
      Oshima, Tokunoshima and Okinawa. A phospholipase A2 (PLA2) of basic nature (pI
      8.5) was isolated from the venom of Amami-Oshima T. flavoviridis. Its amino acid
      sequence determined by the ordinary procedures was completely in accord with that
      predicted from the nucleotide sequence of the cDNA previously cloned from Amami
      Oshima T. flavoviridis venom gland, which was named PLA-B'. It consists of 122
      amino acid residues and has aspartate at position 49. It induced edema in a mouse
      footpad assay and caused necrosis in mouse skeletal muscles. PLA-B' is similar in
      sequence to PLA-B (Tokunoshima) and PL-Y (Okinawa), both basic [Asp49]PLA2s, with
      a few amino acid substitutions, indicating occurrence of interisland mutation.
      Although PLA2s of Crotalinae subfamily were phylogenetically classified into four
      types, PLA2 (acidic or neutral [Asp49]PLA2) type, basic [Asp49]PLA2 type,
      neurotoxic [Asp49]PLA2 type and [Lys49]PLA2 type, it was ascertained that PLA2s
      of PLA2 type and [Lys49]PLA2 type are most essential as toxic components for
      Crotalinae snake venoms and that basic [Asp49]PLA2-type PLA2s are uniquely
      contained only in the venoms of T. flavoviridis species. Prediction of
      physiological activities of some PLA2s was made based on their location in the
      phylogenetic tree. Relationship of divergence of PLA2s via accelerated evolution
      followed by less rapid mutation and physiological activities was discussed.

PMID- 15972223
TI  - Variations of respiratory activity and glutathione in activated sludges exposed
      to low ozone doses.
AB  - Ozonation is one of the most effective treatments for reducing the production of
      activated sludges in wastewater treatment plants. However, because microorganisms
      are present in the form of microcolonies, some bacteria may be exposed to sub
      lethal ozone doses that could lead to adaptation and resistance to further
      exposition to oxidative treatment. This represents a major question as it may
      limit the effect of the treatment, especially when low ozone doses are applied.
      The critical ozone dosage, defined as the lowest specific transferred ozone
      concentration leading to a decrease in the maximum oxygen uptake rate was
      estimated to range between 0.9 and 13.6mg O(3)g(-1) COD(sludges), according to
      the sludges tested. The lowest ozone dosage leading to the decrease of GSH and
      GSHt concentrations could be estimated to be lower than 10mg O(3)g(-1)
      COD(sludges) for GSH, and close to 10mg O(3)g(-1) COD(sludges) for GSHt. After
      sludge exposure to low ozone doses, no higher amounts of glutathione were
      synthesized, suggesting that no development of resistance to ozonation occurred
      after sludge treatment with low ozone doses.

PMID- 15972224
TI  - The impact of floc size on respiration inhibition by soluble toxicants--a
      comparative investigation.
AB  - Activated sludge facilities are susceptible to upset by shock loads of toxic
      compounds. We hypothesized that floc size plays an important role in determining
      the sensitivity of mixed liquor to shock by cadmium and 2,4-dinitrophenol (DNP).
      To test this hypothesis, heterotrophic respiration inhibition experiments were
      conducted using mixed liquor from a pilot-scale membrane bioreactor (MBR) and
      full-scale activated sludge (FSAS) facility with gravity settling secondary
      clarifiers that were operated under similar process conditions. MBR mixed liquor
      flocs were both 41% smaller and 2 and 1.25 times more sensitive to equivalent
      soluble cadmium and DNP concentrations, respectively, compared to FSAS mixed
      liquor flocs. Similarly, FSAS mixed liquor that had been sheared (resulting in a
      smaller average floc diameter) was 1.5 times more sensitive to soluble cadmium
      than non-sheared FSAS mixed liquor. These results suggest that activated sludge
      process conditions that create smaller floc particles, such as the use of
      membranes for liquid-solid separation, are more susceptible to upset events
      caused by shock loads of cadmium and DNP. The particle size distribution (PSD)
      and average floc diameter of a mixed liquor suspension should be measured and
      reported when stating the inhibition concentration of a specific toxicant.

PMID- 15972225
TI  - Effects of acid treatments of activated carbon on its physiochemical structure as
      a support for copper oxide in DeSO(2) reaction catalysts.
AB  - To enhance the dispersion of active sites, modification of the AC supports with
      different acid solution might result in various surface oxygen groups which act
      as anchoring sites for metallic precursor to stay and improve the reactivity
      between AC supports and copper precursor. In the present work, the AC support is
      tailored with HCl and HNO(3), respectively. The pore structure, surface oxygen
      groups of the AC support and catalysts as well as catalyst dispersion before and
      after acid treatments are systematically studied by BET, pH(slurry), TPD, and
      XRPD analyses. It is found that the order of activity in DeSO(2) reaction is as
      follows: Cu/AC-HCl>Cu/AC>Cu/AC-HNO(3). The same sequence is also observed for the
      pore structure of AC supports, the catalyst dispersion, but not for the amounts
      of CO(2) evolving during TPD experiments of supports. The key role of acid
      treatment on carbon surface chemistry and pore structure, which are closely
      related to catalyst dispersion and adsorption capacity, is examined to
      rationalize these findings. Furthermore, under the NO/NH(3)=1 the NO could be
      selective catalytic reduction with NH(3) in the presence of O(2), which catalyzed
      by fresh and spent AC-supported catalyst.

PMID- 15972226
TI  - Effect of arsenic on chloroplast ultrastructure and calcium distribution in
      arsenic hyperaccumulator Pteris vittata L.
AB  - This study investigated the impacts of arsenic (As) on the chloroplast
      ultrastructure and calcium (Ca) distribution in Chinese brake (Pteris vittata L.)
      mainly by histochemical methods, with an emphasis on the possible function of Ca
      in As detoxification and accumulation in P. vittata. P. vittata was grown in an
      artificially contaminated soil added with different concentrations of
      Na(2)HAsO(4) (0, 100, 300 and 800 mg kg(-1) As dry soil) for 24 weeks in a
      greenhouse. The addition of As did not affect the chloroplast ultrastructure of
      young pinna, meanwhile most of the membrane systems of chloroplasts in mature
      pinna were severely damaged under high As condition. Calcium concentration in the
      fronds of P. vittata was not significantly affected by the addition of As, but Ca
      concentration in the mature pinna significantly increased by As addition,
      consistent with the position appearing As toxicity. When no As was added, most of
      calcium precipitates distributed around the inner membrane of vacuole. But when
      the pinna appeared plasmolysis, more calcium precipitates resided outside the
      cell membrane and bigger particles evenly distributed in the cytoplasm. All the
      results indicated that Ca had a close relation with As toxicity in P. vittata.

PMID- 15972227
TI  - Organochlorine pesticides (DDTs and HCHs) in soils from the outskirts of Beijing,
      China.
AB  - Concentrations of HCH (hexachlorocyclohexane) and DDT
      (Dichlorodiphenyltrichloroethane) were determined in shallow subsurface (5-30 cm
      depth) and deep soil layers (150-180 cm depth) from the outskirts of Beijing,
      China. Concentrations of total HCHs (including alpha, beta, gamma, delta-isomers)
      and total DDTs (including p,p'-DDT, p,p'-DDE, p,p'-DDD, o,p'-DDT) in shallow
      subsurface soils ranged from 1.36 to 56.61 ng/g dw (median 5.25 ng/g), and from
      0.77 to 2178 ng/g (median 38.66 ng/g), respectively, and those in the deeper
      layers were approximately an order of magnitude less. The spatial distribution of
      HCHs and DDTs reflected the known historical usage of these pesticides. No
      correlation between the concentrations of pesticides and soil organic matter
      content or clay content can be found. The factors affecting residue levels and
      compositions of DDT and HCH were discussed. The contour maps of beta/gamma ratios
      and DDT/DDE ratios for both the shallow subsurface and deep layer soils were
      drawn.

PMID- 15972228
TI  - Manganese concentrations in the soil and air in the vicinity of a closed
      manganese alloy production plant.
AB  - In Montreal (Canada), the mean annual atmospheric Mn concentrations between 1981
      and 1990 were stable, followed by a decrease of almost 50% from 1990 to 1992. The
      reason for such a decrease in Mn is probably the shutdown of a large manganese
      alloy production plant in Beauharnois, approximately 25 km from Montreal. The
      objective of this study is to assess the level of air and soil contamination by
      Mn in the vicinity of this ferroalloy plant more than 10 years after its closure.
      Air and soil were sampled over 5 days at two and three sites, respectively. Site
      1 was located 10 m NE of the closed plant, in the direction of the prevailing SW
      NE winds. Sites 2 and 3 were at 50 and 800 m SE from the plant. Air samples were
      collected in order to determine total (MnT) and respirable (MnR). Soil samples
      were taken in the surface and subsurface strata. The results show that site 1 is
      extremely polluted with a mean Mn concentration in surface strata of 2,66,000+/
      45,000 ppm and 2,83,000+/-23,000 ppm in the subsurface strata, while the average
      MnT and MnR are 21.9+/-13.7 and 3.5+/-3.9 microg/m(3), respectively. The
      explanation for this contamination is direct deposition on the soil of solid Mn
      rich residue and atmospheric erosion of Mn particles. The situation should be
      remediated by the public authority with high priority.

PMID- 15972229
TI  - Is phenol condensation one of the major pathways in the formation of
      polychlorinated dibenzofurans in municipal waste incinerators?: Model prediction
      vs. field observation.
AB  - The role of phenol condensation pathways in the formation of polychlorinated
      dibenzofurans (PCDF) in a municipal waste incinerator was assessed by comparing
      predicted PCDF homologue and isomer patterns with those obtained from the
      incinerator. A two-phenol condensation model, dependent only on the distribution
      of phenols, was used to predict the distributions of PCDF congeners in the
      incinerator. Complete distributions of phenols and PCDF congeners were obtained
      from the incinerator. To quantify the degree of agreement between obtained isomer
      distributions and those predicted by the model, R-squared values from linear
      correlations were calculated for the dichlorinated- through hexachlorinated
      isomers. They ranged from 0.001 to 0.1. Agreement between obtained and predicted
      PCDF isomers was very poor for all homologues, suggesting that phenol
      condensation pathways are unlikely to be the primary route in the formation of
      PCDF in the incinerator. However, dibenzofuran (DF) is likely to be produced from
      a condensation of two phenols. This paper shows the use of PCDF homologue and
      isomer patterns calculated by the two-phenol condensation model for testing PCDF
      formation mechanism attribution in a municipal waste incinerator.

PMID- 15972230
TI  - Acute and early life stage toxicity of industrial effluent on Japanese medaka
      (Oryzias latipes).
AB  - To develop the whole effluent toxicity testing methods (WET), embryo larval stage
      toxicity test using Japanese medaka (Oryzias latipes) was conducted to evaluate
      an effluent from a banknote printing plant (BPP). The method is based on acute
      toxicity using endpoint of 96-h larval morality and on chronic toxicity using
      endpoints such as the time to hatch, hatching success, deformity, growth rate,
      swim-up failure, accumulative mortality and sexual ratio. In test for 96-h larval
      mortality, LC50 (the concentration was lethal to 50% of newly hatching medaka
      larvae) was 72.9%. In chronic toxicity test, newly fertilized embryos (<5-h old)
      were exposed to 1%, 6.25%, 12.5%, 25%, 50% effluent concentrations and to 200
      mug/l BPA in a 24-h static renewal system at 25+/-1 degrees C until 15 day post
      hatch. The results showed that all chronic endpoints were significantly different
      from the control at 50% dilution (p < 0.01). Embryos began to show lesions on 4th
      day at higher concentrations (12.5%, 25%, 50% BPP effluent concentrations).
      Treatment group of 25% dilution showed delayed time to hatch. A reduction in body
      weight was observed at 25% dilutions for males and females, respectively.
      Deformities were observed in newly hatched larvae at 25% and 50% BPP effluent
      concentrations. At 25% dilution, sex ratio of larvae was alternated and there was
      feminization phenomenon. We conclude that embryo larval stage test using medaka
      is feasible to evaluate both acute and chronic toxicities and potential endocrine
      disrupting activity of industrial effluents.

PMID- 15972231
TI  - Monitoring Pt and Rh in urban aerosols from Buenos Aires, Argentina.
AB  - Vehicular traffic is the main source of platinum group elements (PGEs) in highly
      populated urban areas like Buenos Aires where a traffic density of 1,500,000
      vehicles day(-1) (corresponding to 7,500 vehicles km(-2)) is estimated. Since
      there is no information on the levels of PGEs in Buenos Aires, a pilot study was
      undertaken to ascertain the amount of two major PGEs, namely Pt and Rh, in the
      atmosphere of this city. To this end, 49 samples of PM-10 particulate matter were
      collected during 7 days in seven representative sampling sites located downtown
      Buenos Aires and spread over an area of about 30 km(2). The collection of
      particulate matter was performed on ash-free glass-fiber filters using high
      volume samplers with PM-10 sampling heads. Filters loaded with the particulate
      matter were subjected to microwave (MW)-assisted acid digestion using a
      combination of HNO(3), HF and HClO(4). The resulting solutions were evaporated
      and then diluted with 0.1 mol l(-1) HCl. Analyses were performed by sector field
      inductively coupled plasma-mass spectrometry (SF-ICP-MS) and special attention
      was paid to the control of mass interferences. Statistical analysis was performed
      on the experimental data obtained for the element concentrations taking also into
      account local meteorological data for the monitored period. The highest
      concentrations of Pt and Rh were detected at two sites (Hospital Aleman and Casa
      Rapallini) located in streets with traffic consisting mostly of passenger cars.
      The Pt content (in pg m(-3)) in airborne particulate matter was found to vary
      from 2.3 to 47.7, with a mean value of 12.9+/-7, and that of Rh from 0.3 to 16.8,
      with a mean value of 3.9+/-2.8. These concentrations are by far below the levels
      for which adverse health effects might be expected to occur, i.e., around 100 ng
      m(-3). On the other hand, monitoring of PGEs should be carried out in a
      systematic fashion to detect possible dramatic increases from today's levels.

PMID- 15972232
TI  - Endometrial carcinosarcomas have a different prognosis and pattern of spread
      compared to high-risk epithelial endometrial cancer.
AB  - OBJECTIVE: The endometrial origin of uterine carcinosarcoma has recently been
      well established. The current study investigates whether uterine carcinosarcomas
      can be included in protocols on high-risk endometrial cancer, given the
      similarities in biologic behavior of both entities. METHODS: Pathological and
      surgical notes of patients diagnosed with grade 3 endometrioid, carcinosarcoma,
      serous and clear cell endometrial cancer subtypes were retrospectively analyzed
      with special attention to the spread pattern of the different subtypes.
      Information on site of relapse and time to recurrence was obtained. RESULTS: We
      traced 146 patients of which 9 patients were ineligible. Histological subtypes of
      the remaining 137 patients were as follows: 50 (37%) grade 3 endometrioid
      carcinoma, 54 (39%) serous or clear cell carcinoma (non-endometrioid carcinoma),
      and 33 (24%) carcinosarcomas. Distribution of early stage disease (I and II) was
      67, 46, and 78% for grade 3 endometrioid, non-endometrioid, and carcinosarcoma,
      respectively. Although we could not trace differences in hematogenic and
      transperitoneal spread among the three subtypes, non-endometrioid and
      carcinosarcomas were more likely to spread to pelvic and paraaortic lymph nodes
      (P < 0.01). Using univariate analysis, both stage (P < 0.006, Wald statistic) and
      histological type appear to determine the outcome, whereas lymphovascular space
      infiltration (P < 0.25) and age (P < 0.07) were not significantly different
      between the three histological subtypes. Cox Regression multivariate analysis on
      127 women suffering from the three histological subtypes suggested that both
      stage III-IV disease (P < 0.00001) and histological type (carcinosarcoma) (P <
      0.003) were of prognostic significance [hazard ratio (CI 95%) were, respectively,
      3.8 (2.1-7.0) and 3.2 (1.7-5.9)]. Analyzing cases limited to stage I-II
      endometrial cancer, 24/28 (86%) grade 3 endometrioid, 18/24 (75%) non
      endometrioid, and 11/25 (44%) carcinosarcomas survived, suggesting a worse
      outcome for endometrial carcinosarcoma when compared to the other subtypes (P <
      0.008, Log Rank). A higher incidence of pulmonary metastases explained the worse
      outcome for early stage carcinosarcoma (P < 0.006), whereas the incidence of
      liver metastasis, transperitoneal spread, or recurrences in lymph nodes or vagina
      were comparable between the three pathologic subtypes. CONCLUSIONS: Although
      endometrial carcinosarcoma originates from epithelial cancer, the intrinsic more
      aggressive tumor biology suggests that this subtype should not be incorporated in
      studies on high-risk epithelial endometrial cancer.

PMID- 15972233
TI  - Cognitive enhancement in aged rats after chronic administration of Equisetum
      arvense L. with demonstrated antioxidant properties in vitro.
AB  - The aim of this work was to verify if chronic administration of the
      hydroalcoholic extract of stems from Equisetum arvense (HAE) reverses the
      cognitive impairment in aged rats, as well as, evaluates it in vitro antioxidant
      properties. Chronic administration of HAE at dose of 50 mg/kg, i.p., improved
      both short- and long-term retention of inhibitory avoidance task and ameliorated
      the cognitive performance in reference and working memory version of the Morris
      Water Maze. No differences were found between all three groups of young controls,
      aged controls and EHA-treated animals with regard to the open field and elevated
      plus maze tests. Indeed, no toxicity manifestations were observed during
      treatment. In vitro assays revealed that HAE diminished the thiobarbituric acid
      reactive substances as well as nitrite formation, but did not alter catalase
      activity. Thus, the cognitive enhancement effects of the HAE may be attributed,
      at least in part, to it antioxidant action.

PMID- 15972235
TI  - Interaction between O-carboxymethylchitosan and dipalmitoyl-sn-glycero-3
      phosphocholine bilayer.
AB  - O-carboxylmethylchitosan (OCMCS), a chitosan derivative, has emerged as a strong
      polymeric biomembrane perturbant. In this study, the interaction between OCMCS
      and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was examined with cross
      polarization microscopy, differential scanning calorimetry (DSC) and the surface
      pressure-area isotherms techniques. Cross-polarized light images showed that
      OCMCS induced the fusion of small DPPC multilamellar vesicles (MLV) to form large
      lamellar structures. From DSC measurement, the highest degree of fusion was found
      at the optimum OCMCS concentrations between 0.0625 and 0.2 mg/ml which are orders
      of magnitude lower than those required for similar reductions with unmodified
      chitosan as perturbant. At these concentrations, the association of DPPC and
      OCMCS enhances the fusion of DPPC vesicles. Surface pressure-area isotherms of
      DPPC monolayer in the presence of OCMCS imply interactions between OCMCS and DPPC
      in neutral condition. In comparison with chitosan, OCMCS proved to be a more
      effective membrane perturbant not only in neutral but also in acidic and basic
      conditions. The physical driving forces for OCMCS-induced perturbation of DPPC
      bilayer in neutral conditions are mainly hydrogen bonding and hydrophobic
      interactions. In acidic or basic conditions, the physical driving forces are
      dominated by the electrostatic interactions. The strong OCMCS-DPPC interaction
      will potentially increase the effectiveness of OCMCS for gene or drug delivery.

PMID- 15972234
TI  - Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A
      receptor expression in discrete brain areas.
AB  - Activation of 5-HT2A receptors has been shown to be an essential component of the
      discriminative stimulus effects of indoleamine and phenethylamine hallucinogens.
      The objective of the present study was to determine the neuroanatomical location
      of the 5HT2A receptors which may be responsible for the stimulus effects of the
      phenethylamine hallucinogen [-]2,5-dimethoxy-4-methylamphetamine (DOM). It was
      hypothesized that brain areas containing altered 5-HT2A receptor expression in
      the context of a similar alteration in DOM-induced stimulus control might be
      important in mediating the stimulus effects of DOM. Fisher 344 rats were treated
      with either clozapine (25 mg/kg/day) or DOM (2 mg/kg/day) for 7 days, and the
      consequences of these drug treatment regimens on DOM-induced stimulus control and
      on 5-HT2A receptor expression in several brain areas were determined. Chronic
      administration of clozapine was associated with a wide-spread decrease in levels
      of 5-HT2A/2C receptors. Conversely, treatment with DOM had varied effects
      including a neuroanatomically selective decrease in 5-HT2A/2C receptor levels
      that was restricted to the olfactory nucleus. Both chronic treatment with DOM and
      clozapine decreased the stimulus effects of DOM. The present findings suggest a
      role for the olfactory nucleus in producing the stimulus effects of DOM.

PMID- 15972236
TI  - Tuning compliance of nanoscale polyelectrolyte multilayers to modulate cell
      adhesion.
AB  - It is well known that mechanical stimuli induce cellular responses ranging from
      morphological reorganization to mineral secretion, and that mechanical
      stimulation through modulation of the mechanical properties of cell substrata
      affects cell function in vitro and in vivo. However, there are few approaches by
      which the mechanical compliance of the substrata to which cells adhere and grow
      can be determined quantitatively and varied independent of substrata chemical
      composition. General methods by which mechanical state can be quantified and
      modulated at the cell population level are critical to understanding and
      engineering materials that promote and maintain cell phenotype for applications
      such as vascular tissue constructs. Here, we apply contact mechanics of
      nanoindentation to measure the mechanical compliance of weak polyelectrolyte
      multilayers (PEMs) of nanoscale thickness, and explore the effects of this
      tunable compliance for cell substrata applications. We show that the nominal
      elastic moduli E(s) of these substrata depend directly on the pH at which the
      PEMs are assembled, and can be varied over several orders of magnitude for given
      polycation/polyanion pairs. Further, we demonstrate that the attachment and
      proliferation of human microvascular endothelial cells (MVECs) can be regulated
      through independent changes in the compliance and terminal polyion layer of these
      PEM substrata. These data indicate that substrate mechanical compliance is a
      strong determinant of cell fate, and that PEMs of nanoscale thickness provide a
      valuable tool to vary the external mechanical environment of cells independently
      of chemical stimuli.

PMID- 15972237
TI  - Proinflammatory cytokines and apoptosis following glutamate-induced
      excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats.
AB  - The proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 rise during neuronal
      damage and activate the apoptotic mitogen-activated protein kinase p38. We
      studied apoptosis, the levels of TNF-alpha, IL-1beta, and IL-6, and the cell type
      producing TNF-alpha in rats at 8, 10, and 14 days of age after neonatal exposure
      to glutamate, which induces neuronal damage. TNF-alpha production was
      significantly increased by glutamate, but inhibited by SB203580 (a p38
      inhibitor). TNF-alpha, IL-1beta, and IL-6 mRNA levels increased, but SB203580 did
      not modify their expression. Thus, the p38 signaling pathway influences the
      expression of inflammatory genes and its inhibition may offer anti-inflammatory
      therapy.

PMID- 15972239
TI  - Extracranial stereotactic radiotherapy for primary and metastatic renal cell
      carcinoma.
AB  - BACKGROUND AND PURPOSE: We investigated the results of using stereotactic
      radiotherapy (SRT) for 58 patients with renal cell carcinomas (RCC) who were
      evaluated restrospectively for response rates, local control rates and side
      effects. PATIENTS AND METHODS: From October 1997 to January 2003, 50 patients
      suffering from metastatic RCC and eight patients with inoperable primary RCC
      received high-dose fraction SRT while placed in a stereotactic body-frame. The
      most common dose/fractionation schedules used were 8 Gyx4, 10 Gyx4 and 15 Gyx3
      during approximately 1 week. RESULTS: SRT-treated tumor lesions regressed totally
      in 30% of the patients at 3-36 months, whereas 60% of the patients had a partial
      volume reduction or no change after a median follow-up of 37 months (SD 17.4) for
      censored and 13 months (SD 12.9) for uncensored patients. Side effects were
      generally mild. Of 162 treated tumors, only three recurred, yielding a local
      control rate of 90-98%, considering the 8% non-evaluable sites as defined here.
      For patients with one to three metastases, the time to new spread was 9 months.
      CONCLUSIONS: Our use of SRT for patients with primary and metastatic RCC yielded
      a high local control rate with low toxicity. Patients with one to three
      metastases, local recurrences after nephrectomy or inoperable primary tumors
      benefited the most, i.e. had fewer distant recurrences (13/23) and longer
      survival times compared to patients with >3 metastases (24/27 recurrences).

PMID- 15972238
TI  - Elevated immunoglobulin levels in the cerebrospinal fluid from lupus-prone mice.
AB  - The systemic autoimmune disease lupus erythematosus (SLE) is frequently
      accompanied by neuropsychiatric manifestations and brain lesions of unknown
      etiology. The MRL-lpr mice show behavioral dysfunction concurrent with
      progression of a lupus-like disease, thus providing a valuable model in
      understanding the pathogenesis of autoimmunity-induced CNS damage. Profound
      neurodegeneration in the limbic system of MRL-lpr mice is associated with
      cytotoxicity of their cerebrospinal fluid (CSF) to mature and immature neurons.
      We have recently shown that IgG-rich CSF fraction largely accounts for this
      effect. The present study examines IgG levels in serum and CSF, as well as the
      permeability of the blood-brain barrier in mice that differ in immune status,
      age, and brain morphology. In comparison to young MRL-lpr mice and age-matched
      congenic controls, a significant elevation of IgG and albumin levels were
      detected in the CSF of aged autoimmune MRL-lpr mice. Two-dimensional gel
      electrophoresis and MALDI-TOF MS confirmed elevation in IgG heavy and Ig light
      chain isoforms in the CSF. Increased permeability of the blood-brain barrier
      correlated with neurodegeneration (as revealed by Fluoro Jade B staining) in
      periventricular areas. Although the source and specificity of neuropathogenic
      antibodies remain to be determined, these results support the hypothesis that a
      breached blood-brain barrier and IgG molecules are involved in the etiology of
      CNS damage during SLE-like disease.

PMID- 15972240
TI  - Clinical quality assurance for 106Ru ophthalmic applicators.
AB  - BACKGROUND AND PURPOSE: Episcleral brachytherapy using 106Ru/106Rh ophthalmic
      applicators is a proven method of therapy of uveal melanomas sparing the globe
      and in many cases sparing the vision. In the year 2001, an internal clinical
      quality assurance procedure revealed that part of the ophthalmic applicators
      leaked and that the calibration was erroneous. Consequently, the producer
      modernized its production procedures and, in May 2002, introduced a dose rate
      calibration that is traceable to the NIST standard. This NIST calibration
      confirmed that the previous calibration had been incorrect. In order to study the
      effects of the producer's new internal quality assurance procedures on the
      ophthalmic applicators, applicators of this new generation were submitted to a
      newly improved internal clinical acceptance test. PATIENTS AND METHODS: The
      internal clinical acceptance test consists of a leakage test and a dosimetric
      test of the ophthalmic applicators. The leakage test simulates contact of the
      ophthalmic applicators with chloride containing body fluid. The dosimetric tests
      measure depth dose curves and dose rate with a plastic scintillator dosimetric
      system and compare them with the indications in the producer's certificate.
      Furthermore, the depth dose profile of the most frequently used applicator (type
      CCB) was compared with published data. RESULTS: The internal clinical leakage
      test showed that all of the tested ophthalmic applicators belonging to the new
      generation (n=17) were tight and not contaminated. The dosimetric acceptance
      tests applied to seven different types of applicators revealed that the relative
      depth dose profiles in the therapeutically relevant range (up to a depth of <or=7
      mm) deviate from the producer's indications only by -2.7 to +3.2%. The acceptance
      test of the dose rate values of the ophthalmic applicators at a distance of 2mm
      from the surface of the applicators resulted in a coefficient of variation of
      1.7% (n=17). In the evaluation of the depth dose profile of the type CCB
      applicator the producer's indications and the results of the entrance test
      conformed very well to published data. CONCLUSIONS: The internal clinical quality
      assurance procedure has proved successful in three ways. (1) It had a catalytic
      effect that led to the development of a new generation of ophthalmic applicators.
      (2) It could be demonstrated that this new generation of applicators is up to the
      state of the art in brachytherapy. (3) With this new generation of 106Ru/106Rh
      ophthalmic applicators it is possible for the first time in the history of their
      use to apply the dose that is prescribed by the radiooncologist.

PMID- 15972241
TI  - Controlled release of rhBMP-2 loaded poly(dl-lactic-co-glycolic acid)/calcium
      phosphate cement composites in vivo.
AB  - The release kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2)
      loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement (PLGA/Ca-P
      cement) composites were studied in vivo. RhBMP-2 was radiolabeled with (131)I and
      entrapped within PLGA microparticles or adsorbed onto the microparticle surface.
      PLGA microparticles were prepared of high molecular weight (HMW) PLGA (weight
      average molecular weight [M(w)] 49,100+/-1700) or low molecular weight (LMW) PLGA
      (M(w) 5,900+/-300) and used for preparation of 30:70 wt.% PLGA/Ca-P cement
      composite discs. Release of 131I-rhBMP-2 loaded composites was assessed by
      scintigraphic imaging according to a 2(2) two-level full factorial design in the
      rat ectopic model during four weeks. In vivo release kinetics varied among
      formulations. All formulations showed slow release without initial burst, and
      displayed a linear release from 3 to 28 days. Release of LMW entrapped rhBMP-2
      composites (1.7+/-0.3%/day) was significantly faster than release from other
      formulations (p<0.01). After 28 days, retention within the composites was 65+/
      5%, 75+/-4%, 50+/-4% and 70+/-6% of the initial rhBMP-2 for HMW entrapped, HMW
      adsorbed, LMW entrapped and LMW adsorbed rhBMP-2 composites, respectively.
      Release from the composite was probably slowed down by an interaction of rhBMP-2
      and Ca-P cement after rhBMP-2 release from PLGA microparticles. We conclude that
      PLGA/Ca-P cement composites can be considered as sustained slow release vehicles
      and that the release and retention of rhBMP-2 can be modified according to the
      desired profile to a limited extent.

PMID- 15972242
TI  - Is migration to Canada associated with unhealthy weight gain? Overweight and
      obesity among Canada's immigrants.
AB  - This paper aims to address a gap in our understanding of immigrant health issues
      by examining the determinants of excess weight--an important indicator of current
      and future health. The paper combines data drawn from recent large health surveys
      to identify how the weight of recent immigrants compares with that of native-born
      people, and how the likelihood of becoming overweight or obese changes with
      additional years in Canada. We find evidence that on average, immigrants are
      substantially less likely to be obese or overweight upon arrival in Canada. These
      measures converge slowly to native-born levels, but there is marked variation by
      the ethnicity of the immigrant. Since changes in weight will reflect choices with
      respect to diet and activity, the extent to which overweight and obesity rates
      change with years in Canada may reflect the extent to which immigrants interact
      with or are influenced by members of their ethnic group who reside in the same
      area. We find evidence that ethnic group social network effects exert a
      quantitatively important influence on the incidence of being overweight and obese
      for members of most ethnic minorities, tempering the process of adjustment to
      Canadian lifestyle norms that may be driving excess weight gain with additional
      years in Canada.

PMID- 15972243
TI  - Antioxidant properties of propofol and erythropoietin after closed head injury in
      rats.
AB  - Reactive oxygen species play a role during brain injury due to closed head
      trauma. Enzymatic or nonenzymatic antioxidants may protect brain tissue against
      oxidative damage. The present study was performed to assess the changes of
      endogenous indices of oxidative stress in serum from rats subjected to head
      trauma and whether treatment with propofol and/or erythropoietin (EPO) modifies
      the levels of endogenous indices of oxidative stress. For these purposes, female
      Wistar Albino rats were divided into five groups: non-traumatic sham group,
      trauma performed control, trauma with propofol (i.p.), trauma with EPO (i.p.) and
      trauma with propofol and EPO performed study groups. At the end of the
      experimental procedure, blood was taken by cardiac puncture to determine
      superoxide dismutase (SOD) and xanthine oxidase (XO) activities as well as
      malondialdehyde (MDA) and nitric oxide (NO) levels in serum. Serum MDA level of
      control traumatic brain injury (TBI) group was significantly higher than sham
      operation group (p<0.012). Serum MDA levels in propofol, EPO and propofol+EPO
      groups were found to be decreased in comparison with control group (p<0.039,
      p<0.030 and p<0.018, respectively). Serum NO level was found to be increased in
      TBI group, but difference was not statistically significant when compared to sham
      operated group (p=0.092). Propofol, EPO and propofol+EPO administration
      efficiently reduced serum NO levels to reach sham-operated group (p<0.002,
      p<0.001 and p<0.015, respectively). These results suggested that acute
      administration of both propofol and EPO altered the indices of oxidative stress
      similarly against brain injury due to trauma.

PMID- 15972244
TI  - Reply to Dr. Schmidt's remarks on the paper of H.M. van Praag "Can stress cause
      depression?".

PMID- 15972245
TI  - A cost-effectiveness analysis of heroin detoxification methods in the Australian
      National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD).
AB  - This economic evaluation was part of the Australian National Evaluation of
      Pharmacotherapies for Opioid Dependence (NEPOD) project. Data from four trials of
      heroin detoxification methods, involving 365 participants, were pooled to enable
      a comprehensive comparison of the cost-effectiveness of five inpatient and
      outpatient detoxification methods. This study took the perspective of the
      treatment provider in assessing resource use and costs. Two short-term outcome
      measures were used-achievement of an initial 7-day period of abstinence, and
      entry into ongoing post-detoxification treatment. The mean costs of the various
      detoxification methods ranged widely, from AUD 491 dollars(buprenorphine-based
      outpatient); to AUD 605 dollars for conventional outpatient; AUD 1404 dollars for
      conventional inpatient; AUD 1990 dollars for rapid detoxification under sedation;
      and to AUD 2689 dollars for anaesthesia per episode. An incremental cost
      effectiveness analysis was carried out using conventional outpatient
      detoxification as the base comparator. The buprenorphine-based outpatient
      detoxification method was found to be the most cost-effective method overall, and
      rapid opioid detoxification under sedation was the most cost-effective inpatient
      method.

PMID- 15972246
TI  - An examination of self-medication and rebound effects: Psychiatric symptomatology
      before and after alcohol or drug relapse.
AB  - This study evaluated psychiatric symptoms preceding and following initial
      posttreatment substance use episodes. 125 veterans meeting DSM-IV criteria for
      alcohol, cannabis, and/or stimulant dependence at treatment entry were followed
      with quarterly interviews for one year. Approximately half of the sample met
      criteria for substance use disorders only (n = 65; SUD-only) and half
      additionally met criteria for an independent non-substance related Axis I
      disorder (n = 60; SUD-PSY). SUD-PSY adults reported more psychiatric symptoms
      preceding and following substance use compared to SUD-only adults. Depression and
      anxiety symptoms were commonly reported by both groups. Symptoms typically did
      not change or worsened after substance use, with depression worsening more than
      anxiety or psychotic symptoms. Findings are discussed in relation to the Self
      Medication Hypothesis and the Rebound Hypothesis.

PMID- 15972247
TI  - Liuweidihuang-tang improves spatial memory function and increases neurogenesis in
      the dentate gyrus in rats.
AB  - The aqueous extract of Liuweidihuang-tang given to rats at doses of 100 mg/kg/day
      for 10 days induced a reduction in the frequency of error and increased
      neurogenesis in the hippocampal dentate gyrus. Our data suggest that
      Liuweidihuang-tang improves spatial learning ability by increasing neurogenesis
      in the dentate gyrus.

PMID- 15972248
TI  - Sesquiterpenoids and phenolics from Taraxacum hondoense.
AB  - Eleven sesquiterpene lactones, including the new guaianolide 11beta
      hydroxydeacetylmatricarin-8-O-beta-glucopyranoside, along with four known
      phenolic glucosides were isolated from Taraxacum hondoense. The compounds were
      characterized by spectral methods.

PMID- 15972249
TI  - Sedative and anticonvulsant effects of hydroalcoholic extract of Equisetum
      arvense.
AB  - The hydroalcoholic extract of Equisetum arvense (HAE) tested at the doses of 200
      and 400 mg/kg showed a significant activity on the open-field, enhanced the
      number of falls in the rota-rod reducing the time of permanence in the bar and
      increased the sleeping time (46% and 74%) in the barbiturate-induced sleeping
      time. In the pentylenetetrazole-seizure, it increased the first convulsion
      latency, diminished the severity of convulsions, reduced the percentage of
      animals which developed convulsion (50% and 25%) and protected animals from
      death. On the contrary, in the elevated plus maze, the doses 50, 100 and 150
      mg/kg did not affect the evaluated parameters. Thus, HAE presented anticonvulsant
      and sedative effects. Phytochemical analysis detected the presence of tannins,
      saponins, sterols and flavonoids.

PMID- 15972250
TI  - Cytoprotectivity of Prunella vulgaris on doxorubicin-treated rat cardiomyocytes.
AB  - The cardioprotective effect of Prunella vulgaris ethylacetate fraction (PVEF) and
      its constituent rosmarinic acid (RA) was evaluated on isolated rat cardiomyocytes
      subjected to doxorubicin-induced oxidative stress. The cytoprotectivities of PVEF
      and RA were concentration-dependent in the range of 0.005 to 0.05 mg/ml and the
      effect of PVEF correlated with the RA content. Dexrazoxan (DE), used as positive
      control, was less effective than PVEF or RA.

PMID- 15972251
TI  - Sequence diversity of beta-tubulin (tubA) gene in Phaeosphaeria nodorum and P.
      avenaria.
AB  - Full-length coding sequences of the beta-tubulin gene (tubA) were PCR-amplified
      and sequenced from 42 Phaeosphaeria isolates, including 16 P. nodorum and 23 P.
      avenaria species from cereals, two Polish isolates from rye (Secale cereale L.),
      and one isolate from dallis grass (Paspalum dilatatum Poir). A tubA gene of size
      1556bp was identified in wheat- and barley-biotype P. nodorum (PN-w and PN-b), P.
      avenaria f. sp. avenaria (Paa), homothallic P. avenaria f. sp. triticea (P.a.t.)
      (Pat1) and the P.a.t. isolate (Pat3) from the State of Washington. The tubA gene
      length polymorphisms were detected in two P.a.t. isolates (Pat2) from foxtail
      barley (Hordeum jubatum L.), one from dallis grass and two Polish isolates from
      rye. These size differences were due to the variation of intron lengths among
      these three Phaeosphaeria species. All Phaeosphaeria isolates have identical
      1344bp exons that can be translated into a 447 amino acid beta-tubulin. Like
      glyceraldehyde-3-phosphate dehydrogenase, the beta-tubulin amino acid sequence
      was identical in all Phaeosphaeria species used in this study, with the exception
      of the two Pat2 isolates. Six amino acid differences were evident in the beta
      tubulin of these Pat2 isolates.

PMID- 15972252
TI  - Fructosyl-amino acid oxidases of Aspergillus oryzae are induced by the reaction
      product, glucosone.
AB  - Aspergillus oryzae has two fructosyl-amino acid oxidase (FAOD) isozymes (AoFao1
      and AoFao2), which are different in the substrate specificities. Northern blot
      analysis showed both FAO genes were induced by autoclave-browned medium
      containing l-lysine or l-valine. Studies with a mutant, that had a disrupted
      AoFAO2 gene, revealed that the expression of AoFAO1 by fructosyl l-valine
      depended on the expression of AoFAO2. Both genes were also induced by one of the
      FAOD-reaction products, glucosone. In contrast, other alpha-dicarbonyl compounds,
      which display a similar structure to that of glucosone were not able to induce
      the genes expression. These results imply that glucosone may contribute to the
      expression of FAO genes.

PMID- 15972253
TI  - Nitrate reduction by Desulfovibrio desulfuricans: a periplasmic nitrate reductase
      system that lacks NapB, but includes a unique tetraheme c-type cytochrome, NapM.
AB  - Many sulphate reducing bacteria can also reduce nitrite, but relatively few
      isolates are known to reduce nitrate. Although nitrate reductase genes are absent
      from Desulfovibrio vulgaris strain Hildenborough, for which the complete genome
      sequence has been reported, a single subunit periplasmic nitrate reductase, NapA,
      was purified from Desulfovibrio desulfuricans strain 27774, and the structural
      gene was cloned and sequenced. Chromosome walking methods have now been used to
      determine the complete sequence of the nap gene cluster from this organism. The
      data confirm the absence of a napB homologue, but reveal a novel six-gene
      organisation, napC-napM-napA-napD-napG-napH. The NapC polypeptide is more similar
      to the NrfH subgroup of tetraheme cytochromes than to NapC from other bacteria.
      NapM is predicted to be a tetra-heme c-type cytochrome with similarity to the
      small tetraheme cytochromes from Shewanella oneidensis. The operon is located
      close to a gene encoding a lysyl-tRNA synthetase that is also found in D.
      vulgaris. We suggest that electrons might be transferred to NapA either from
      menaquinol via NapC, or from other electron donors such as formate or hydrogen
      via the small tetraheme cytochrome, NapM. We also suggest that, despite the
      absence of a twin-arginine targeting sequence, NapG might be located in the
      periplasm where it would provide an alternative direct electron donor to NapA.

PMID- 15972254
TI  - Seasonal fluctuations in birth weight and neonatal limb length; does prenatal
      vitamin D influence neonatal size and shape?
AB  - BACKGROUND: Birth weight is known to fluctuate with season of birth, however,
      there is little information about seasonal variation in neonatal anthropometric
      measures. AIMS: The aim of this study was to examine seasonal fluctuations in
      birth weight and selected anthropometric measures. STUDY DESIGN AND SUBJECTS: The
      birth weight of singletons born after at least 37 weeks gestation was extracted
      from a perinatal register in south-east Queensland (n=350,171). Mean monthly
      birth weights for this period were examined. Based on a separate birth cohort,
      principal component analysis was undertaken on neonatal anthropometric measures
      (n=1233). Seasonality was assessed by (a) spectral analysis of time series data,
      (b) monthly and seasonal comparison of outcomes. RESULTS: Based on register data,
      birth weight displayed clear annual periodicity. Birth weight differed
      significantly when compared by month and season. Infants born in October were the
      heaviest (3484 g), while May-born infants were the lightest (3459 g; P=0.001).
      Based on the cohort anthropometric data, three components were identified related
      to (a) overall size, (b) limb length, and (c) head size and skin-fold thickness.
      Each of these components displayed significant seasonal variation. In particular,
      prominent seasonal fluctuations in limb length were identified, with peak limb
      length associated with winter/spring birth. CONCLUSION: Environmental factors
      that have regular seasonal fluctuation influence both the size and shape of
      neonates. Animal experiments suggest that prenatal hypovitaminosis D may underlie
      greater limb length. Because birth weight and limb length are associated with a
      broad range of important health outcomes, the seasonal exposures underlying these
      effects warrant further scrutiny from a public health perspective.

PMID- 15972255
TI  - Respiratory chain complexes and membrane fatty acids composition in rat testis
      mitochondria throughout development and ageing.
AB  - Throughout the maturation of germ cells, a morphological, biochemical and
      functional differentiation of mitochondria has been shown to occur. Ageing is
      known to cause changes involved in energy metabolism. These changes have been
      related to molecular and functional alterations in the properties of biological
      membranes. Variations in membrane lipid composition and lipid-protein
      interactions occur with ageing in several tissues. The present paper describes
      the relationship between these membrane alterations and the activities of lipid
      dependent enzymes of isolated testis mitochondria in rats of from 10 days of age
      to 24 months. The specific activities of these enzymes are lower in preparations
      from adult and aged rats as compared to those from young rats. Temperature breaks
      of Arrhenius plots show age-dependent shifts to higher temperatures for the NADH
      dehydrogenase, succinate-dehydrogenase, cytochrome c oxidase, and ATPase in
      senescent animals. Analysis of the membrane fatty acid composition reveals a
      distinct age-dependent fall in the content of polyunsaturated fatty acids
      accompanied by an increase in the proportion of saturated fatty acids and a
      decrease in polyunsaturated fatty acid percentage. The results suggest that
      during spermatogenesis and the ageing process some changes in the composition of
      the fatty acids in the surrounding membrane affect the protein-lipid
      interactions, producing a decrease in mitochondrial enzyme activities.

PMID- 15972256
TI  - Simultaneous labeling of mast cell proteases and protease mRNAs at the bone
      implant interface of aseptically loosened hip implants.
AB  - Human mast cells (MC) exhibit two distinct phenotypes based on the protease
      content of their secretory granules. MC(TC) cells express tryptase, chymase,
      cathepsin G, and mast cell carboxypeptidase, while MC(T) cells express only
      tryptase. Both mast cell phenotypes were assessed near regions of osteolysis in
      uninfected failed joint implants by immunohistochemistry with antibodies to
      tryptase and chymase, and by in situ hybridization with anti-sense RNA probes for
      the respective mRNA molecules. Specimens from the interface membrane of 32
      aseptically loosened total hip implants were studied, 28 of which had mast cells
      of the MC(TC) type. Most of these mast cells were aligned along the bone
      prosthesis interface adjacent to loosened implants, suggesting involvement in the
      chronic inflammatory response that leads to bone resorption. Further
      ultrastructural evidence of mast cells in tissues from failed joint interface
      membranes was shown by transmission electron microscopy, and detection by
      staining after magnetic activated cell sorting. The presence of MC at the
      periprosthetic interface of eroded bone suggests MC degranulation and activity
      are associated with osteolysis in failed joint prostheses.

PMID- 15972257
TI  - Heterogeneous three-dimensional strain fields during unconfined cyclic
      compression in bovine articular cartilage explants.
AB  - Articular cartilage provides critical load-bearing and tribological properties to
      the normal function of diarthrodial joints. The unique properties of cartilage,
      as well as heterogeneous deformations during mechanical compression, are due to
      the nonuniform microstructural organization of tissue components such as
      collagens and proteoglycans. A new cartilage deformation by tag registration
      (CDTR) technique has been developed by the authors to determine heterogeneous
      deformations in articular cartilage explants. The technique uses a combination of
      specialized MRI methods, a custom cyclic loading apparatus, and image processing
      software. The objective of this study was to use the CDTR technique to document
      strain patterns throughout the volume of normal bovine articular cartilage
      explants during cyclic unconfined compression at two physiologically-relevant
      applied normal stress levels (1.29 and 2.57 MPa). Despite simple uniaxial cyclic
      compressive loading with a flat, nonporous indenter, strain patterns were
      heterogeneous. Strains in the thickness direction (E(yy)) were compressive,
      varied nonlinearly with depth from the articular surface from a maximum magnitude
      of 11% at the articular surface, and were comparable despite a 2-fold increase in
      applied normal stress. Strains perpendicular to the thickness direction (E(xx)
      and E(zz)) were tensile, decreased linearly with depth from the articular surface
      from a maximum of 7%, and increased in magnitude 2.5-fold with a 2-fold increase
      in applied normal stress. Shear strains in the transverse plane (E(xz)) were
      approximately zero while shear strains in the other two planes were much larger
      and increased in magnitude with depth from the articular surface, reaching
      maximum magnitudes of 2% at the articular cartilage-subchondral bone interface.
      In general, strain patterns indicated that cartilage osteochondral explants
      exhibited depth-dependent nonisotropic behavior during uniaxial cyclic loading.
      These results are useful in verifying constitutive formulations of articular
      cartilage during cyclic unconfined compression and in characterizing the
      micromechanical environment likely experienced by individual chondrocytes
      throughout the tissue volume.

PMID- 15972258
TI  - p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the
      MEK1/2-ERK1/2 survival pathway in TNF-alpha induced endothelial apoptosis.
AB  - We recently reported that p38 MAPK regulates TNF-induced endothelial apoptosis
      via phosphorylation and downregulation of Bcl-xL. Here, we describe that such
      apoptosis includes p38 MAPK-mediated, protein phosphatase 2A (PP2A)-dependent,
      downregulation of the MEK-ERK pathway. Inhibition of PP2A with fostriecin or
      calyculin A significantly increased MEK phosphorylation, as did exposure to the
      p38 MAPK inhibitor SB203580. Inhibition of MEK potentiated TNF-induced caspase-3
      activity and cell death, and both those events were suppressed by treatment with
      fostriecin or calyculin A. Immunoprecipitation experiments revealed an
      association between p38 MAPK, PP2A and MEK, and the results of a phosphatase
      assay suggested that PP2A is a downstream target of p38 MAPK. Importantly,
      phosphorylation of Bad at Ser-112 was found to be regulated by p38 MAPK and PP2A.
      In summary, the present findings indicate a novel p38 MAPK-mediated apoptosis
      pathway, involving activation of Bad via PP2A-dependent inhibition of the MEK-ERK
      pathway.

PMID- 15972259
TI  - Dopamine D(4) receptor antagonist 3-(4-[(18)F]fluorobenzyl)-8-methoxy-1,2,3,4
      tetrahydrochromeno[3,4-c]pyridin-5-one([(18)F]FMTP): radiosynthesis and in vivo
      characterization in rats.
AB  - We synthesized a novel (18)F-labeled dopamine D(4) receptor antagonist (Ki=4.3
      nM), 3-(4-[(18)F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin
      5-one ([(18)F]FMTP), which has exhibited high affinity and selectivity.
      Radiosyntheses were accomplished by the reaction of fluorine-18-labeled
      intermediate with 8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one (1)
      followed by HPLC purification. The overall radiochemical yield of the
      radiosynthesis was 19.5% (decay corrected), the specific radioactivity was about
      110 GBq/micromol and the radiochemical purity was greater than 99%, the time of
      synthesis and purification was approximately 110 min. Tissue distribution studies
      of the [(18)F]FMTP in rats showed that the radioactivity in the brain was
      concentrated in frontal cortex and medulla, the region that has a high density of
      D(4) receptors. Pre-treatment with nonradioactive FMTP (1.0mg/kg) produced a
      significant reduction of radioactivity in all the regions. About 40% of total
      radioactivity in plasma and 100% in rat brain extract represented unchanged
      radioligand at 60 min after injection as determined by HPLC. These results
      indicate that [(18)F]FMTP have some specific binding to the D(4) receptor.

PMID- 15972260
TI  - Plastic deformation in structural materials, investigated in situ by neutrons and
      positrons.
AB  - During residual stress measurements by neutron diffraction additional information
      becomes available through the accompanying high-energy prompt capture gamma
      radiation, which in turn produces positrons within the bulk of the specimen.
      Plastic deformation will increase the dislocation density within the material.
      This leads to an increase in the mosaic spread of the diffraction reflections and
      to changes of the lineshape of the positron annihilation radiation. The
      correlation between the width of the Bragg reflections and the S-parameter, which
      describes the shape variation of the annihilation line was investigated as a
      function of the degree of plastic deformation. The experimental work was
      performed at the FRG-I research reactor of GKSS.

PMID- 15972261
TI  - Methadone treatment of chronic non-malignant pain and opioid dependence--a long
      term follow-up.
AB  - Iatrogenic opioid addiction among chronic pain patients was the initiative for
      starting a methadone programme for pain patients at the University Hospital of
      Uppsala. The aims were to improve pain relief and quality of life in pain
      patients with problematic opioid use and to investigate background factors
      explaining problems with opioid use. METHODS: Records of all 60 patients included
      in the methadone programme 1994-2002 were studied. An interview was done after a
      mean of 34 months of methadone treatment regarding pain relief, quality of life
      and side effects on 48 patients. RESULTS: Titration of oral methadone mixture in
      daily doses ranging from 10 to 350 mg (mean 99.5 mg) was done on all patients.
      Background factors were low back and musculoskeletal pain in 40%, psychiatric
      disease in 68%, and substance use disorder in 32% of the patients. Before
      methadone treatment all patients were on sick leave. After treatment five
      patients returned to work. Ten patients failed treatment, 4 due to intractable
      nausea, 4 to drug diversion, 1 because of methadone related arrhythmia and 1
      because of insufficient analgesia. Pain relief was rated good by 75% and moderate
      by 25% of the patients. Global quality of life was rated at mean of 50(0-100),
      which favourably compares with Swedish chronic pain patients mean 33(0-100).
      CONCLUSION: A structured methadone programme can be used for treating chronic
      pain patients with opioid dependence improving pain relief and quality of life.
      However, side effects and serious adverse events may limit the beneficial effects
      of the method.

PMID- 15972262
TI  - Can attitudes of stoicism and cautiousness explain observed age-related variation
      in levels of self-rated pain, mood disturbance and functional interference in
      chronic pain patients?
AB  - The aims of the present study were (a) to examine the relationship between age,
      attitudes and self-reported pain and suffering in a sample of chronic pain
      patients and (b) to determine the extent to which attitudes of stoicism and
      cautiousness might mediate between age and chronic pain experience. Psychometric
      measures were administered to 338 chronic pain patients. The results indicate
      that there were significant relationships between both age and attitudes with
      measures of pain, mood disturbance and functional interference. Attitudes were
      found to provide either a full or partial mediation of the relationship between
      age and various measures of chronic pain experience, thus emphasizing the
      importance of including these cognitive variables for clinical assessment. It
      appears that attitudes of stoicism may be more important than age as a predictor
      of self-reported pain severity. However, with respect to mood and functional
      disturbance, age and perhaps, other age-related factors, remain important
      additional predictors.

PMID- 15972263
TI  - Rapid pulse length determination in high-resolution NMR.
AB  - The 90 degrees (1H) pulse length can be determined in a single scan using a
      simple homo-gated decoupling/nutation experiment. We show that the method is
      fast, accurate and readily amenable to automation.

PMID- 15972264
TI  - Signal identification in NMR spectra with coupled evolution periods.
AB  - Novel multidimensional NMR experiments rely on modified time-domain sampling
      schemes to provide significant savings of experimental time. Several approaches
      are based on the coupling of evolution times resulting in a reduction of the
      dimensionality of the recorded spectra, and a concomitant saving of experimental
      time. We present a consistent and general tool, called EVOCOUP, for the analysis
      of these reduced dimensionality spectra. The approach is flexible in the sense
      that the input can consist of various forms of reduced dimensionality spectra,
      that any piece of information can be removed (provided enough information is
      left), e.g., signals undetectable due to poor signal-to-noise or covered by
      artifacts, and that it can be applied to spectra involving any number of nuclei.
      The use of a general optimization procedure and an appropriate target function
      provides for a robust approach with well-defined results and ensures optimal use
      of redundant information normally present in the input. Spectral overlap in the
      directly detected dimension is resolved in a fully automated manner, avoiding the
      assessment of signal quality and its use in combinatorial trials. The positions
      of all peaks in a corresponding full-dimensional spectrum are obtained without
      need for reconstruction of this spectrum. In a systematic analysis of a complete
      spectrum recorded for the 14 kDa protein azurin and involving five different
      nuclei, only four spin systems were missed and no false spins systems were
      detected.

PMID- 15972265
TI  - Differential requirements of calcium for oxoglutarate dehydrogenase and
      mitochondrial nitric-oxide synthase under hypoxia: impact on the regulation of
      mitochondrial oxygen consumption.
AB  - Studies with isolated mitochondria are performed at artificially high pO(2) (220
      to 250 microM oxygen), although this condition is hyperoxic for these organelles.
      It was the aim of this study to evaluate the effect of hypoxia (20-30 microM) on
      the calcium-dependent activation of 2-oxoglutarate dehydrogenase (or 2
      ketoglutarate dehydrogenase; OGDH) and mitochondrial nitric-oxide synthase
      (mtNOS). Mitochondria had a P/O value 15% higher in hypoxia than that in
      normoxia, indicating that oxidative phosphorylation and electron transfer were
      more efficiently coupled, whereas the intramitochondrial free calcium
      concentrations were higher (2-3-fold) at lower pO(2). These increases were
      abrogated by ruthenium red indicating that the higher uptake via the calcium
      uniporter was involved in this process. Mitochondria at high calcium
      concentration microdomains may produce nitric oxide, given the K(0.5) of calcium
      for OGDH (0.16 microM) and mtNOS (approximately 1 microM). Nitric oxide, by
      binding to cytochrome oxidase in competition with oxygen, decreases the rate of
      oxygen consumption. This condition is highly beneficial for the following
      reasons: i, these mitochondria are still able to produce ATP and support calcium
      clearance; ii, it prevents the accumulation of ROS by slowing the rate of oxygen
      consumption (hence ROS production); iii, the onset of anoxia is delayed, allowing
      oxygen to diffuse back to these sites, thereby ameliorating the oxygen gradient
      between regions of high and low calcium concentration. In this way, oxygen
      depletion at the latter sites is prevented. This, in turn, assures continued
      aerobic metabolism which may involve the activated dehydrogenases.

PMID- 15972266
TI  - Ustilagic acid secretion by Pseudozyma fusiformata strains.
AB  - Eight strains of Pseudozyma fusiformata were examined for antifungal activity.
      All of them had the same spectrum of action and were active against many species
      of yeasts, yeast-like and filamentous fungi. They secreted glycolipids, which
      were purified from the culture liquid by column and thin-layer chromatography.
      According to nuclear magnetic resonance and mass-spectroscopy experiments all
      strains produced ustilagic acid, a cellobioside-containing 2,15,16
      trihydroxypalmitic acid as aglycon, 3-hydroxycaproic acid and acetic acid as O
      acylic substituents.

PMID- 15972267
TI  - Ligand-induced thermostability in proteins: thermodynamic analysis of ANS-albumin
      interaction.
AB  - A comparative thermodynamic study of the interaction of anilinonaphthalene
      sulfonate (ANS) derivatives with bovine serum albumin (BSA) was performed by
      using differential scanning calorimetry (DSC) and isothermal titration
      calorimetry (ITC). The chemically related ligands, 1,8-ANS and 2,6-ANS, present a
      similar affinity for BSA with different binding energetics. The analysis of the
      binding driving forces suggests that not only hydrophobic effect but also
      electrostatic interactions are relevant, even though they have been extensively
      used as probes for non-polar domains in proteins. Ligand association leads to an
      increase in protein thermostability, indicating that both dyes interact mainly
      with native BSA. ITC data show that 1,8-ANS and 2,6-ANS have a moderate affinity
      for BSA, with an association constant of around 1-9x10(5) M(-1) for the high
      affinity site. Ligand binding is disfavoured by conformational entropy. The
      theoretical model used to simulate DSC data satisfactorily reproduces
      experimental thermograms, validating this approach as one which provides new
      insights into the interaction between one or more ligands with a protein. By
      comparison with 1,8-ANS, 2,6-ANS appears as a more "inert" probe to assess
      processes which involve conformational changes in proteins.

PMID- 15972268
TI  - Approximate linear confidence and curvature of a kinetic model of dodecanedioic
      acid in humans.
AB  - Dicarboxylic acids with an even number of carbon atoms have been proposed as an
      alternate energy substrate for enteral or parenteral nutrition in the acutely ill
      patient, due to their water solubility and their yielding TCA cycle intermediates
      upon beta-oxidation. In the present work, a nonlinear compartmental model of the
      kinetics of dodecanedioic acid is developed, and its parameters are estimated
      from time concentration experimental observations obtained from six healthy
      volunteers undergoing a per os administration of 3 g of the substance. Although
      the model is linear in the transfer of the free substance from plasma to the
      tissues, the exchange between gut and plasma compartments is represented as a
      saturable function. Albumin binding is then incorporated to obtain the final
      model in terms of the measured total concentrations. Estimates of the model's
      structural parameters were computed for each experimental subject, and the usual
      single-subject approximate confidence regions for the parameters were derived by
      inversion of the Hessian at the optimum. To verify the applicability of this
      approximation, the nonlinearity of the expectation surface at the optimum was
      measured by computing the normal (intrinsic) component of curvature. Because the
      model curvature was excessive in all subjects, the usual approximation could not
      be trusted to provide acceptable approximations to the parameter confidence
      regions. A suitable Monte Carlo simulation yielded empirical joint parameter
      distributions from which the approximate parameter variances could finally be
      obtained.

PMID- 15972269
TI  - Measurement of selective effect of insulin on glucose disposal from labeled
      glucose oral test minimal model.
AB  - The oral glucose minimal model (OMM) measures insulin sensitivity (S(I)) and the
      glucose rate of appearance (R(a)) of ingested glucose in the presence of
      physiological changes of insulin and glucose concentrations. However, S(I) of OMM
      measures the overall effect of insulin on glucose utilization and glucose
      production. In this study we show that, by adding a tracer to the oral dose,
      e.g., of a meal, and by using the labeled version of OMM, OMM* to interpret the
      data, one can measure the selective effect of insulin on glucose disposal, S(I)*.
      Eighty-eight individuals underwent both a triple-tracer meal with the tracer-to
      tracee clamp technique, providing a model-independent reference of the R(a) of
      ingested glucose (R(a meal)(ref)) and an insulin-modified labeled intravenous
      glucose tolerance test (IVGTT*). We show that OMM* provides not only a reliable
      means of tracing the R(a) of ingested glucose (R(a meal)) but also accurately
      measures S(I)*. We do so by comparing OMM* R(a meal) with the model-independent
      R(a meal)(ref) provided by the tracer-to-tracee clamp technique, while OMM* S(I)*
      is compared with both S(I)(* ref), obtained by using as known input R(a
      meal)(ref), and with S(I)* measured during IVGTT*.

PMID- 15972270
TI  - Collagen synthesis in human musculoskeletal tissues and skin.
AB  - We have developed a direct method for the measurement of human musculoskeletal
      collagen synthesis on the basis of the incorporation of stable isotope-labeled
      proline or leucine into protein and have used it to measure the rate of synthesis
      of collagen in tendon, ligament, muscle, and skin. In postabsorptive, healthy
      young men (28 +/- 6 yr) synthetic rates for tendon, ligament, muscle, and skin
      collagen were 0.046 +/- 0.005, 0.040 +/- 0.006, 0.016 +/- 0.002, and 0.037 +/-
      0.003%/h, respectively (means +/- SD). In postabsorptive, healthy elderly men (70
      +/- 6 yr) the rate of skeletal muscle collagen synthesis is greater than in the
      young (0.023 +/- 0.002%/h, P < 0.05 vs. young). The rates of synthesis of tendon
      and ligament collagen are similar to those of mixed skeletal muscle protein in
      the postabsorptive state, whereas the rate for muscle collagen synthesis is much
      lower in both young and elderly men. After nutrient provision, collagen synthesis
      was unaltered in tendon and skeletal muscle, remaining at postabsorptive values
      (young: tendon, 0.045 +/- 0.008%/h; muscle, 0.016 +/- 0.003%/h; elderly: muscle,
      0.024 +/- 0.003%/h). These results demonstrate that the rate of human
      musculoskeletal tissue collagen synthesis can be directly and robustly measured
      using stable isotope methodology.

PMID- 15972271
TI  - Determination of triglyceride in the human myocardium by magnetic resonance
      spectroscopy: reproducibility and sensitivity of the method.
AB  - The primary aim of this investigation was to determine the reliability and
      sensitivity of 1H magnetic resonance spectroscopy (1H-MRS) as a method for
      quantifying myocardial triglyceride (TG) content in humans over time and in
      response to metabolic perturbations. Three separate experiments were designed to
      quantify myocardial TG content 1) over a 90-day period, 2) after a high-fat meal,
      and 3) after a 48-h fast. Proton spectra were collected from a 10 x 20 x 30-mm3
      voxel placed within the intraventricular septum, with measurements acquired at
      end-systole and end-expiration, using cardiac triggering and respiratory gating.
      Minimal variation was observed between myocardial TG content determined 90 days
      apart (r = 0.98, CV = 5%), whereas TG values were unaffected by a high-fat meal
      despite a significant twofold increase (P < 0.05) in serum TG. In contrast,
      myocardial TG content increased threefold (P < 0.05) after a 48-h fast despite a
      25% reduction in serum TG. Body mass index was significantly related to
      myocardial TG (r = 0.58, P < 0.05) and the change in myocardial TG after a 48-h
      fast (r2 = 0.60). 1H-MRS is a reliable method for the determination of myocardial
      TG in humans and is relatively unaffected by the consumption of one high-fat meal
      but sensitive to changes following a prolonged fast.

PMID- 15972272
TI  - Reciprocal changes in endogenous ghrelin and growth hormone during fasting in
      healthy women.
AB  - Ghrelin stimulates growth hormone (GH) secretion, but it is unknown whether there
      is a feedback of GH on ghrelin secretion. In this study, we characterized the
      relatedness of GH and ghrelin in a model of acute caloric deprivation in 10
      healthy women (age 26.7 +/- 1.6 yr) during a 4-day fast in the early follicular
      phase. GH, ghrelin, and cortisol were assessed every hour over 24 h during an
      isocaloric diet and after a 4-day complete fast. Sampling during a normal diet at
      baseline demonstrated that ghrelin decreased 17.9% within 1 h after meals (P <
      0.0001), but there was no meal effect on GH. BMI (22.3 +/- 0.4 vs. 21.5 +/- 0.4
      kg/m2, P < 0.0001) and IGF-I (312 +/- 28 vs.124 +/- 22 ng/ml, P < 0.0001)
      decreased during fasting. Mean 24-h GH increased (2.6 +/- 0.5 vs. 5.6 +/- 0.5
      ng/ml, P < 0.001), but ghrelin decreased (441.3 +/- 59.7 vs. 359.8 +/- 54.2
      pg/ml, P = 0.012). The peak ghrelin level decreased from 483.5 to 375.6 pg/ml (P
      < 0.0001), and the time of the peak ghrelin changed from 0415 to 1715. In
      contrast, the diurnal pattern of GH was maintained, with increases in the nadir
      (1.1 to 3.4 ng/ml) and peak GH concentrations (4.1 to 7.9 ng/ml) from the fed to
      fasted state (P < 0.0001). The change in morning GH concentrations was inversely
      related to the change in ghrelin (r = -0.79, P = 0.012). During complete short
      term caloric deprivation in healthy women, ghrelin decreases, even as GH rises,
      and these processes appear to be reciprocal, suggesting that GH exhibits feedback
      inhibition on ghrelin. Our data provide new evidence of the physiological
      relationship of GH and ghrelin in response to changes in protein-energy
      metabolism.

PMID- 15972273
TI  - On the suppression of plasma nonesterified fatty acids by insulin during enhanced
      intravascular lipolysis in humans.
AB  - During the fasting state, insulin reduces nonesterified fatty acid (NEFA)
      appearance in the systemic circulation mostly by suppressing intracellular
      lipolysis in the adipose tissue. In the postprandial state, insulin may also
      control NEFA appearance through enhanced trapping into the adipose tissue of NEFA
      derived from intravascular triglyceride lipolysis. To determine the contribution
      of suppression of intracellular lipolysis in the modulation of plasma NEFA
      metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10
      healthy nonobese subjects underwent pancreatic clamps at fasting vs. high
      physiological insulin level with intravenous infusion of heparin plus Intralipid.
      Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to
      inhibit intracellular lipolysis and assess insulin's effect on plasma NEFA
      metabolism independently of its effect on intracellular lipolysis. Stable isotope
      tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA
      metabolism and total triglyceride lipolysis in each participant. The glycerol
      appearance rate was similar during fasting vs. high insulin level, but plasma
      NEFA levels were significantly lowered by insulin. Nicotinic acid significantly
      blunted the insulin-mediated suppression of plasma palmitate appearance and
      oxidation rates by approximately 60 and approximately 70%, respectively. In
      contrast, nicotinic acid did not affect the marked stimulation of palmitate
      clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA
      appearance and oxidation can be explained by suppression of intracellular
      lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans.
      Our results also suggest that insulin may affect plasma NEFA clearance
      independently of the suppression of intracellular lipolysis.

PMID- 15972274
TI  - Zone-specific cell proliferation during adrenocortical regeneration after
      enucleation in rats.
AB  - A quantitative analysis of zone-specific proliferation was done to determine the
      recovery of adrenal cortical zonation during regeneration after enucleation.
      Adult male rats underwent adrenal enucleation [unilateral enucleation (ULE)] or
      sham surgery, both accompanied by contralateral adrenalectomy. At 2, 5, 10, and
      28 days, blood and adrenals were collected to assess functional recovery. Adrenal
      sections were immunostained for Ki67 (proliferation), cytochrome P-450
      aldosterone synthase (P-450aldo, glomerulosa), and cytochrome P-450 11beta
      hydroxylase (P-45011beta, fasciculata). Unbiased stereology was used to count
      proliferating glomerulosa and fasciculata cells. Recovery of fasciculata
      secretory function occurred by 28 days as reflected by plasma ACTH and
      corticosterone, whereas glomerulosa function reflected by plasma aldosterone
      remained low at 28 days. At 5 days, ULE adrenals showed increased Ki67+ cells in
      the glomerulosa and inner fasciculata, whereas at 10 and 28 days increased
      proliferation was restricted to the outer fasciculata. These data show that
      enucleation results in transient elevations in glomerulosa and inner fasciculata
      cell proliferation followed by a delayed increase in the outer fasciculata. To
      assess adrenal growth in enucleated adrenals previously suppressed by the
      presence of an intact adrenal, rats underwent ULE and sham surgery; after 4 wk,
      the intact adrenal was removed and enucleated adrenals were collected at 2, 5,
      and 10 days. Overall, proliferation was delayed in this model, but at 5 days,
      Ki67+ cells increased in the outer fasciculata, whereas by 10 days, increased
      proliferation occurred in the outer and inner fasciculata. The key novel finding
      of increased proliferation in the inner fasciculata suggests that the delayed
      growth of the enucleated adrenal results in part from a regenerative response.

PMID- 15972275
TI  - The association between stress and drinking: modifying effects of gender and
      vulnerability.
AB  - AIMS: To assess the relationship between number and type of past-year stressful
      experiences and alcohol consumption, with a focus on how gender, poverty, and
      psychological vulnerability moderate this association. METHODS: Data from 26 946
      US past-year drinkers 18 years of age and over, interviewed in the 2001-2002
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), were
      used to construct multivariate linear regression models predicting six measures
      of drinking pattern and volume. RESULTS: There was a consistent positive
      relationship between number of past-year stressors experienced and all measures
      of heavy drinking. Frequency of heavy (5+ drinks for men; 4+ drinks for women)
      drinking increased by 24% with each additional stressor reported by men and by
      13% with each additional stressor reported by women. In contrast, the frequency
      of moderate drinking (<5 drinks for men; <4 drinks for women) decreased as stress
      levels increased. Job-related and legal sources of stress were more strongly
      associated with alcohol consumption than were social and health-related stress.
      Men showed a stronger association than women between the number of stressors and
      the most consumption measures; they also responded more strongly to the presence
      of any legal and job-related stress. Having an income below the poverty level
      intensified the effects of job-related stress, but having a mood or anxiety
      disorder did not affect any of the associations between stress and consumption.
      CONCLUSIONS: Stress does not so much lead individuals to drink more often as to
      substitute larger quantities of alcohol on the days when they do drink. Treatment
      and brief interventions aimed at problem drinkers might benefit from addressing
      the issue of tension alleviation and the development of alternative coping
      mechanisms.

PMID- 15972276
TI  - Limitations of molecular detection of CK19 mRNA-positive cells in the peripheral
      blood of breast cancer patients with histologically negative axillary lymph
      nodes.

PMID- 15972277
TI  - Vascular endothelial growth factor (VEGF) expression is not associated with
      prognosis in patients with radically resected ampullary carcinoma.

PMID- 15972278
TI  - Spectrum of breast cancer metastasis in BRCA1 mutation carriers: highly increased
      incidence of brain metastases.

PMID- 15972280
TI  - An association of sarcoidosis with hepatocellular carcinoma.

PMID- 15972281
TI  - Cerebrospinal fluid diffusion of Zevalin after high-activity treatment and stem
      cell support in a patient affected by diffuse large B-cell non-Hodgkin's lymphoma
      with central nervous system involvement.

PMID- 15972282
TI  - Reply to the article "The significance of skeletal-related events for the health
      related quality of life of patients with metastatic prostate cancer" by K. P.
      Weinfurt et al. (Ann Oncol 2005; 16: 579-584).

PMID- 15972283
TI  - Trichomegaly of the eyelashes following treatment with cetuximab.

PMID- 15972284
TI  - BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology
      categories in biological networks.
AB  - The Biological Networks Gene Ontology tool (BiNGO) is an open-source Java tool to
      determine which Gene Ontology (GO) terms are significantly overrepresented in a
      set of genes. BiNGO can be used either on a list of genes, pasted as text, or
      interactively on subgraphs of biological networks visualized in Cytoscape. BiNGO
      maps the predominant functional themes of the tested gene set on the GO
      hierarchy, and takes advantage of Cytoscape's versatile visualization environment
      to produce an intuitive and customizable visual representation of the results.

PMID- 15972285
TI  - MARNA: multiple alignment and consensus structure prediction of RNAs based on
      sequence structure comparisons.
AB  - MOTIVATION: Due to the importance of considering secondary structures in aligning
      functional RNAs, several pairwise sequence-structure alignment methods have been
      developed. They use extended alignment scores that evaluate secondary structure
      information in addition to sequence information. However, two problems for the
      multiple alignment step remain. First, how to combine pairwise sequence-structure
      alignments into a multiple alignment and second, how to generate secondary
      structure information for sequences whose explicit structural information is
      missing. RESULTS: We describe a novel approach for multiple alignment of RNAs
      (MARNA) taking into consideration both the primary and the secondary structures.
      It is based on pairwise sequence-structure comparisons of RNAs. From these
      sequence-structure alignments, libraries of weighted alignment edges are
      generated. The weights reflect the sequential and structural conservation. For
      sequences whose secondary structures are missing, the libraries are generated by
      sampling low energy conformations. The libraries are then processed by the T
      Coffee system, which is a consistency based multiple alignment method.
      Furthermore, we are able to extract a consensus-sequence and -structure from a
      multiple alignment. We have successfully tested MARNA on several datasets taken
      from the Rfam database.

PMID- 15972287
TI  - Limited diagnostic yield of non-invasive coronary angiography by 16-slice multi
      detector spiral computed tomography in routine patients referred for evaluation
      of coronary artery disease.
AB  - AIMS: Multislice spiral computed tomography (MSCT) is a promising non-invasive
      method to diagnose coronary artery disease (CAD). As no detailed comparative
      evaluation in consecutive patients referred for evaluation of CAD has been
      reported, this prospective study evaluating 2384 coronary segments in 149
      consecutive patients was performed. METHODS AND RESULTS: The coronary artery tree
      was analysed in 16 segments both for coronary angiography (CA) and MSCT; a
      luminal narrowing > or = 50% based on visual assessment was considered
      significant. By MSCT, 77% of 2110 angiographically assessable segments could be
      evaluated, 94% per patient in proximal and 70% in distal segments (P<0.001).
      Sensitivity of MSCT to detect significant stenoses was 30% in all, but only 10%
      in peripheral segments. The main limitations were calcifications in 34% of
      segments and motion artefacts in 24% of patients. Overall diagnostic sensitivity
      for the presence of significant CAD was 86% but specificity was only 49%.
      CONCLUSION: When compared with invasive CA, 16-slice MSCT is of limited
      diagnostic value for the diagnosis of CAD in consecutive patients. Despite a
      clinically useful sensitivity for the overall diagnosis of significant CAD,
      specificity is low. Thus, relevant decisions regarding the need of and
      suitability for possible revascularization procedures cannot be based on MSCT
      findings alone.

PMID- 15972288
TI  - Detecting acute coronary syndrome in the emergency department: the answer is in
      seeing the heart: why look further?

PMID- 15972289
TI  - Lipids and CVD management: towards a global consensus.
AB  - Cardiovascular disease (CVD) is currently the leading cause of morbidity and
      mortality worldwide and its incidence is likely to increase. Multiple risk
      factors contribute to CVD. Elevated LDL-cholesterol (LDL-C) and triglyceride
      levels, low HDL-cholesterol levels, hypertension, type 2 diabetes, and smoking
      are key modifiable risk factors. Such risk factors are present in 80-90% of
      coronary heart disease (CHD) patients. For many factors, modification can
      significantly reduce CVD incidence. For example, statin-induced LDL-C reductions
      reduce cardiovascular events by 24-37% and smoking cessation reduces CHD
      mortality by 36%. The need to identify and treat these risk factors has led many
      national and local groups to develop clinical practice guidelines for management
      of CVD. Although the aim of such guidelines is to provide practitioners with a
      framework to identify, prioritize, and manage patients, the plethora of
      guidelines can cause confusion. In addition, research indicates that guidelines
      are not being optimally implemented. This review considers these practical
      issues, highlights the common goals shared by many guidelines, and focuses on how
      these can be best achieved. It also highlights areas where the guidelines differ
      and discusses points to consider when selecting the most appropriate
      recommendation.

PMID- 15972290
TI  - Impact of ventricular response irregularity in patients with atrial fibrillation
      and heart failure.

PMID- 15972291
TI  - Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall
      imaging.
AB  - AIMS: Although the coronary artery vessel wall can be imaged non-invasively using
      magnetic resonance imaging (MRI), the in vivo reproducibility of wall thickness
      measures has not been previously investigated. Using a refined magnetization
      preparation scheme, we sought to assess the reproducibility of three-dimensional
      (3D) free-breathing black-blood coronary MRI in vivo. METHODS AND RESULTS: MRI
      vessel wall scans parallel to the right coronary artery (RCA) were obtained in 18
      healthy individuals (age range 25-43, six women), with no known history of
      coronary artery disease, using a 3D dual-inversion navigator-gated black-blood
      spiral imaging sequence. Vessel wall scans were repeated 1 month later in eight
      subjects. The visible vessel wall segment and the wall thickness were
      quantitatively assessed using a semi-automatic tool and the intra-observer, inter
      observer, and inter-scan reproducibilities were determined. The average imaged
      length of the RCA vessel wall was 44.5+/-7 mm. The average wall thickness was
      1.6+/-0.2 mm. There was a highly significant intra-observer (r=0.97), inter
      observer (r=0.94), and inter-scan (r=0.90) correlation for wall thickness (all
      P<0.001). There was also a significant agreement for intra-observer, inter
      observer, and inter-scan measurements on Bland-Altman analysis. The intra-class
      correlation coefficients for intra-observer (r=0.97), inter-observer (r=0.92),
      and inter-scan (r=0.86) analyses were also excellent. CONCLUSION: The use of
      black-blood free-breathing 3D MRI in conjunction with semi-automated analysis
      software allows for reproducible measurements of right coronary arterial vessel
      wall thickness. This technique may be well-suited for non-invasive longitudinal
      studies of coronary atherosclerosis.

PMID- 15972292
TI  - Free wall rupture in the elderly: deleterious effect of fibrinolytic therapy on
      the ageing heart.

PMID- 15972293
TI  - Heart failure on admission and the risk of stroke following acute myocardial
      infarction: the VALIANT registry.
AB  - AIMS: We sought to assess the relative contribution of heart failure (HF) on
      admission for an acute myocardial infarction (MI) to the subsequent in-hospital
      stroke risk. METHODS AND RESULTS: The VALsartan In Acute myocardial iNfarcTion
      (VALIANT) registry enrolled 5573 consecutive MI patients at 84 international
      sites from 1999 to 2001. We calculated odds ratios (ORs) for stroke and adjusted
      for baseline characteristics, Killip Class, and risk factors for stroke, such as
      diabetes and prior HF. In-hospital stroke occurred in 81 (1.5%) patients. HF was
      present on admission in 38% of patients who developed a stroke and in 24% who did
      not (P=0.001). Older age (OR 1.03 increase/year, 95% confidence interval (CI)
      1.01-1.04), Killip Class III (OR 1.66, CI 0.86-3.19) or IV (OR 4.85, CI 1.69
      13.93), history of hypertension (OR 1.73, CI 1.06-2.82), and history of stroke
      (OR 1.89, CI 1.06-3.37) were more common in patients who had in-hospital stroke.
      In-hospital mortality in patients with and without stroke was 27.2 and 6.5%,
      respectively (P<0.001). CONCLUSION: Patients with stroke after MI have a dismal
      prognosis. The presence of HF on admission for an acute MI increases in-hospital
      stroke risk. HF treatments may modify the risk of stroke.

PMID- 15972294
TI  - In vitro reconstruction of an endothelialized skin substitute provided with a
      microcapillary network using biopolymer scaffolds.
AB  - Successful in vitro reconstruction of skin requires the inclusion of several cell
      types that give rise in coculture to the specific elements present in native
      skin, and the appropriate scaffolding structure to house and support these cells.
      In addition to the two main structural components, epidermis and dermis, one
      critical apparatus of the skin is a capillary network that guarantees adequate
      perfusion of nutrients and oxygen. The aim of the present study was to develop an
      in vitro coculture system that assumed the human dermal-epidermal architecture
      and included a microcapillary network in a three-dimensional biomaterial that
      guaranteed ease of handling in a clinical setting. Endothelialized skin (ES) was
      prepared by coculturing three human cell types: keratinocytes, fibroblasts, and
      endothelial cells, obtained from human full-thickness skin samples, in scaffolds
      produced from modified hyaluronic acid. Results were evaluated by histological
      and immunohistochemical analyses at different time points. In vitro, engineered
      skin obtained with this composite culture developed into a well-differentiated
      upper layer of stratified keratinocytes lining a dermal-like structure, in which
      fibroblasts, extracellular matrix and a microvascular network were present.
      Furthermore, the biodegradable fabric produced from hyaluronic acid and used as
      the scaffolding support for this in vitro constructed skin graft greatly
      facilitated handling in the perioperative period.

PMID- 15972295
TI  - Serotonergic-like progenitor cells propagated from neural stem cells in vitro:
      survival with SERT protein expression following implantation into brains of mice
      lacking SERT.
AB  - Neural stem cells (NSCs) obtained from the midbrain region of embryonic (E14)
      mice were initially cultured with basic fibroblast growth factor (bFGF), Sonic
      hedgehog, and FGF-8 in a serum-free N-2 culture medium to foster differentiation
      into a serotonergic-like phenotype. During the initial differentiating phase,
      these progenitor cells expressed En1, Pax3, and Pax5 mRNA. Subsequently, a single
      serotonin [5-hydroxytryptamine (5-HT)] and tryptophan hydroxylase-positive clone
      was isolated, which gave rise to cells that developed serotonergic properties.
      Sixty percent of these progenitor cells expressed the serotonin transporter
      (SERT), as indicated by specific ligand binding of [125I]-RTI-55. To further
      evaluate SERT functionality, we showed that these progenitor cells possessed
      specific [3H]-5-HT uptake activity. Implantation of the serotonergic-like
      progenitors into the hippocampus of adult mice genetically lacking SERT was
      followed by migration of these cells into adjacent brain regions, and survival of
      the cells at 8 weeks was accompanied by a gradual increase in density of SERT
      protein expression, which was not found in vehicle-injected, control mice. These
      findings suggest that this serotonergic-like NSC model will be a useful
      contribution to the development of cell biotechnology in regard to the expression
      of missing genes such as SERT in the adult brain.

PMID- 15972296
TI  - Genomic structure and functional characterization of the human ADAM10 promoter.
AB  - The ADAM10 gene encodes a membrane-bound disintegrin-metalloproteinase, which,
      after overexpression in an Alzheimer disease (AD) mouse model, prevents amyloid
      pathology and improves long-term potentiation and memory. Because enhancing
      ADAM10 expression appears to be a reasonable approach for treatment of AD, we
      functionally analyzed the ADAM10 gene. Both human and mouse ADAM10 genes comprise
      approximately 160 kbp, are composed of 16 exons, and are evolutionarily highly
      conserved within 500 bp upstream of either translation initiation site. By using
      luciferase reporter assays, we demonstrate that nucleotides -2179 to -1 upstream
      of the human ADAM10 translation initiation site represent a functional TATA-less
      promoter. Within this region we identified and examined several single nucleotide
      polymorphisms, but did not detect significant differences in their appearance
      between AD and nondemented control subjects. By deletion analysis, site-directed
      mutagenesis, transcription factor overexpression and electrophoretic mobility
      shift assays, we identified nucleotides -508 to -300 as the core promoter and
      found Sp1, USF, and retinoic acid-responsive elements to modulate its activity.
      Finally, we identified vitamin A acid (RA) as an inducer of human ADAM10 promoter
      activity. This finding suggests that pharmacologic targeting of RA receptors may
      increase the expression of the alpha-secretase ADAM10 with beneficial effects on
      AD pathology.

PMID- 15972297
TI  - Oxidative Bax dimerization promotes its translocation to mitochondria
      independently of apoptosis.
AB  - Bax is a cytosolic protein, which in response to stressing apoptotic stimuli, is
      activated and translocates to mitochondria, thus initiating the intrinsic
      apoptotic pathway. In spite of many studies and the importance of the issue, the
      molecular mechanisms that trigger Bax translocation are still obscure. We show by
      computer simulation that the two cysteine residues of Bax may form disulfide
      bridges, producing conformational changes that favor Bax translocation.
      Oxidative, nonapoptogenic treatments produce an up-shift of Bax migration
      compatible with homodimerization, which is reverted by reducing agents; this is
      accompanied by translocation to mitochondria. Dimers also appear in pure
      cytosolic fractions of cell lysates treated with H2O2, showing that Bax
      dimerization may take place in the cytosol. Bax dimer-enriched lysates support
      Bax translocation to isolated mitochondria much more efficiently than untreated
      lysates, indicating that dimerization may promote Bax translocation. The absence
      of apoptosis in our system allows the demonstration that Bax moves because of
      oxidations, even in the absence of apoptosis. This provides the first evidence
      that Bax dimerization and translocation respond to oxidative stimuli, suggesting
      a novel role for Bax as a sensor of redox imbalance.

PMID- 15972298
TI  - Randomised controlled trial of azathioprine and 5-aminosalicylic acid for
      treatment of steroid dependent ulcerative colitis.
AB  - BACKGROUND AND AIMS: There are limited evidence based data concerning the use of
      azathioprine in ulcerative colitis. We aimed to compare the efficacy of
      azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid
      dependent ulcerative colitis. METHODS: Seventy two patients with steroid
      dependent ulcerative colitis were admitted to this investigator-blind study.
      Steroid dependence was defined as a requirement for steroid therapy > or =10
      mg/day during the preceding six months, with at least two attempts to discontinue
      the medication. The disease had to be clinically and endoscopically active at
      study entry, and all patients were taking systemic prednisolone (40 mg/day).
      Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5
      aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of
      the treatment was defined as (1) success, indicating induction of clinical and
      endoscopic remission and steroid discontinuation, or (2) failure, indicating the
      absence of clinical and endoscopic remission and therefore the need for at least
      one further cycle of systemic steroids to control symptoms, apart from the
      initial one, or colectomy. RESULTS: Significantly more patients in the
      azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic
      remission, and discontinued steroid therapy, both in the intention to treat
      (azathioprine v 5-aminosalicylic acid: 19/36 patients (53%) v 7/36 (21%); odds
      ratio (OR) 4.78 (95% confidence interval (CI) 1.57-14.5)) and per protocol
      (azathioprine v 5-aminosalicylic acid: 19/33 patients (58%) v 7/34 (21%); OR 5.26
      (95% CI 1.59-18.1)) analysis. CONCLUSIONS: Azathioprine is significantly more
      effective than 5-aminosalicylic acid in inducing clinical and endoscopic
      remission and avoiding steroid requirement in the treatment of steroid dependent
      ulcerative colitis.

PMID- 15972299
TI  - Effect of physical activity and body size on survival after diagnosis with
      colorectal cancer.
AB  - BACKGROUND: Physical inactivity and obesity increase the risk of colorectal
      cancer but little is known about whether they influence prognosis after
      diagnosis. METHODS: Incident cases of colorectal cancer were identified among
      participants of the Melbourne Collaborative Cohort Study, a prospective cohort
      study of 41 528 Australians recruited from 1990 to 1994. Participants diagnosed
      with their first colorectal cancer between recruitment and 1 August 2002 were
      eligible. At the time of study entry, body measurements were taken and
      participants were interviewed about their physical activity. Information on
      tumour site and stage, treatments given, recurrences, and deaths were obtained
      from systematic review of the medical records. RESULTS: A total of 526 cases of
      colorectal cancer were identified. Median follow up among survivors was 5.5
      years, and 208 deaths had occurred, including 181 from colorectal cancer. After
      adjusting for age, sex, and tumour stage, exercisers had an improved disease
      specific survival (hazard ratio 0.73 (95% confidence interval (CI) 0.54-1.00)).
      The benefit of exercise was largely confined to stage II-III tumours (hazard
      ratio 0.49 (95% CI 0.30-0.79)). Increasing per cent body fat resulted in an
      increase in disease specific deaths (hazard ratio 1.33 per 10 kg (95% CI 1.04
      1.71)). Similarly, increasing waist circumference reduced disease specific
      survival (hazard ratio 1.20 per 10 cm (95% CI 1.05-1.37)). CONCLUSIONS: Increased
      central adiposity and a lack of regular physical activity prior to the diagnosis
      of colorectal cancer is associated with poorer overall and disease specific
      survival.

PMID- 15972300
TI  - Anticipation in familial pancreatic cancer.
AB  - BACKGROUND: Previous studies of anticipation in familial pancreatic cancer have
      been small and subject to ascertainment bias. Our aim was to determine evidence
      for anticipation in a large number of European families. PATIENTS AND METHODS: A
      total of 1223 individuals at risk from 106 families (264 affected individuals)
      were investigated. Generation G3 was defined as the latest generation that
      included any individual aged over 39 years; preceding generations were then
      defined as G2 and G1. RESULTS: With 80 affected child-parent pairs, the children
      died a median (interquartile range) of 10 (7, 14) years earlier. The median
      (interquartile range) age of death from pancreatic cancer was 70 (59, 77), 64
      (57, 69), and 49 (44, 56) years for G1, G2, and G3, respectively. These
      indications of anticipation could be the result of bias. Truncation of Kaplan
      Meier analysis to a 60 year period to correct for follow up time bias and a
      matched test statistic indicated significant anticipation (p=0.002 and p<0.001).
      To minimise bias further, an iterative analysis to predict cancer numbers was
      developed. No single risk category could be applied that accurately predicted
      cancer cases in every generation. Using three risk categories (low with no
      pancreatic cancer in earlier generations, high with a single earlier generation,
      and very high where two preceding generations were affected), incidence was
      estimated without significant error. Anticipation was independent of smoking.
      CONCLUSION: This study provides the first strong evidence for anticipation in
      familial pancreatic cancer and must be considered in genetic counselling and the
      commencement of secondary screening for pancreatic cancer.

PMID- 15972301
TI  - Prevalence of acid reflux in functional dyspepsia and its association with
      symptom profile.
AB  - AIM: A subset of functional dyspepsia patients respond to acid suppressive
      therapy, but the prevalence of non-erosive reflux disease in functional dyspepsia
      and its relevance to symptoms have never been established. The aim of the present
      study was to study 24 hour pH monitoring in consecutive functional dyspepsia
      patients. METHODS: A total of 247 patients with dyspeptic symptoms (166 women,
      mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and
      without dominant symptoms of heartburn participated in the study. In all
      patients, the severity of dyspeptic symptoms and the presence of heartburn was
      assessed by a questionnaire and a 24 hour oesophageal pH monitoring study was
      performed. All patients underwent a gastric emptying breath test and in 113 a
      gastric barostat study was performed. RESULTS: Abnormal pH monitoring (acid
      exposure >5% of time) was found in 58 patients (23%). Of 21 patients with a
      positive heartburn questionnaire, 76% had pathological pH monitoring, while this
      was the case in only 18.5% of patients with a negative heartburn questionnaire.
      Demographic characteristics and the prevalence of other pathophysiological
      mechanisms did not differ between heartburn negative patients with normal or
      abnormal acid exposure. Pathological acid exposure in heartburn negative patients
      was associated with the presence of epigastric pain (65 v 84%, p<0.005) and of
      moderate or severe pain (48 v 69%, p = 0.005). CONCLUSION: Pathological
      oesophageal acid exposure is only present in a subset of heartburn negative
      functional dyspepsia patients, which are characterised by a higher prevalence of
      epigastric pain.

PMID- 15972302
TI  - Responsive evaluation in health promotion: its value for ambiguous contexts.
AB  - Responsive evaluation offers a perspective in which evaluation is reframed from
      the assessment of program interventions on the basis of policymakers' goals to an
      engagement with all stakeholders about the value and meaning of their practice.
      This article argues for this perspective both generally and more particularly in
      relation to health promotion. Responsive evaluation is especially appropriate in
      health promotion contexts characterized by a high degree of ambiguity. Ambiguity
      refers to the absence of or contradictory interpretations about what needs to,
      can and should be done, when and where. Ambiguity is high in the case of non
      routine programs, lack of knowledge about success indicators, collaborative and
      community based programs and the absence of consensus among stakeholders. In
      health promotion contexts marked by a low degree of ambiguity random controlled
      trials (RCTs) and quantitative methods are to be considered. This implies the
      evaluators should assess the degree of ambiguity of a situation before deciding
      about an appropriate design.

PMID- 15972303
TI  - Pilot study in the development of an interactive multimedia learning environment
      for sexual health interventions: a focus group approach.
AB  - In the UK there are high rates of sexually transmitted infections and unintended
      pregnancies amongst young people. There is limited and contradictory evidence
      that current sexual health education interventions are effective or that they
      improve access to appropriate sexual health services. This paper describes the
      outcome of focus group work with young people that was undertaken to inform the
      design of an Interactive Multimedia Learning Environment that incorporates
      message framing, intended for use in sexual health promotion. The focus group
      work addressed sexual attitudes, behaviour, risk perception, and knowledge of
      sexual health and sexual health services in Nottingham. The results provided new
      insights into young peoples' sexual behaviour, and their diversity of knowledge
      and beliefs. Common themes expressed regarding sexual health services included
      concerns about confidentiality, lack of confidence to access services and fear of
      the unknown. The results showed that while the adolescents are reasonably
      knowledgeable about infection, they do not know as much about the relevant
      services to treat it. This work emphasizes the need for user involvement
      throughout the design and development of a sexual health intervention, and will
      form the basis of the next part of the project.

PMID- 15972304
TI  - Delayed expansion of a restricted T cell repertoire by low-density TCR ligands.
AB  - The role of TCR ligand density (i.e. the number of antigen-MHC complexes) in
      modulating the diversity of a T cell response selected from a pool of naive
      precursors remains largely undefined. By measuring early-activation markers up
      regulation and proliferation following stimulation with staphylococcal
      enterotoxin A (SEA), we demonstrate that decreasing the ligand dose below an
      optimal concentration leads to the delayed activation of a restricted set of
      TCRVbeta-bearing T cells, with the specific, non-stochastic exclusion of some
      TCRVbeta+ T cells from the activated pool. Our results suggest that the failure
      of these TCRVbeta-bearing T cells to reach the activation threshold at sub
      optimal ligand concentration is due to the inefficiency of TCR engagement, as
      measured by TCR internalization, and does not correlate with the relative
      precursor frequency in the non-immune repertoire. Moreover, even at SEA
      concentrations that lead to the simultaneous proliferation of all SEA-reactive T
      cells, we observe marked differences in the ability to secrete cytokines among
      the different responsive TCRVbeta-bearing T cells. Altogether, our results
      indicate that the development of a T cell response to a scarce display of ligand
      significantly narrows TCR repertoire diversity by mechanisms that involve
      focusing of the repertoire on the expansion of those T cells with the highest
      avidity of TCR engagement.

PMID- 15972305
TI  - Commentary: Adding to our comprehension of Gulf War health questions.

PMID- 15972307
TI  - Mathematical model--tell us the future!
AB  - Studying bacterial resistance has direct importance for the antimicrobial
      treatment of individual patients. In addition, surveillance data pooled from
      individual diagnostic reports help physicians to choose the most effective drug
      for empirical therapy. However, this is not the limit of what can be done with
      the resistance data. There is an increasing need to synthesize the available
      strands of data in order to construct mathematical models that can be used as
      tools to predict the likely outcomes of various antibiotic policy options.

PMID- 15972308
TI  - The resistance ratchet: theoretical implications of cyclic selection pressure.
AB  - OBJECTIVES: To investigate the effects of cyclic antibiotic selection pressure on
      resistance in a simple mathematical model. METHODS: The model assumed that
      resistance in microbial ecologies changes slowly with changing selection
      pressure, at a rate proportional to the difference between the current resistance
      level and the resistance level that would be in equilibrium with current
      selection pressure. The maximum rate of increase in resistance during periods of
      increasing selection was assumed to be greater than the maximum rate of decrease
      during decreased selection. RESULTS: Under a simulated annual cyclic selection
      pressure variation of 40%, with maximum resistance rise and fall rates of 10 and
      0.5%, respectively, resistance rose above the level expected from the mean
      selection pressure by small ratchet-like increments. Over 50 simulated years,
      resistance increased to 62%, rather than the 50% expected from the mean level of
      selection. Welsh community prescribing for a selection of antibiotics showed a
      seasonal cyclic variation of 13-45%. CONCLUSIONS: The intuitive assumption that
      cyclic selective pressure would produce resistance levels commensurate with the
      mean selection pressure was contradicted; rather resistance drifted towards a
      level commensurate with maximum selection pressure. If the ratchet effect exists
      in reality, it may produce unexpected excess resistance, particularly in the
      community for antibiotics used in respiratory infection, where cycling is
      pronounced, or in ITU antibiotic rotation. It should be most pronounced for
      resistance systems with strong asymmetry between rates of adaptation under rising
      and falling selection pressure. Non-linear dynamic systems in physics and ecology
      are notorious for producing counter-intuitive effects; resistance epidemiology
      may be similar.

PMID- 15972309
TI  - tet(L)-mediated tetracycline resistance in bovine Mannheimia and Pasteurella
      isolates.
AB  - OBJECTIVES: Tetracycline-resistant Mannheimia and Pasteurella isolates, which
      were negative for the tetracycline resistance genes (tet) commonly detected among
      these bacteria, were investigated for other tet genes present and their location.
      METHODS: Mannheimia and Pasteurella isolates were investigated for their MICs of
      tetracycline and their plasmid content. Identification of tet genes was achieved
      by PCR. Plasmids mediating tetracycline resistance were identified by
      transformation and hybridization experiments. Plasmid pCCK3259 from Mannheimia
      haemolytica was sequenced completely and analysed for its structure and
      organization. RESULTS: All tetracycline-resistant isolates carried the gene
      tet(L) either on plasmids or on the chromosome. Two M. haemolytica isolates and
      one Mannheimia glucosida isolate harboured a common 5.3 kb tet(L) plasmid,
      designated pCCK3259. This plasmid was similar to the tet(B)-carrying tetracycline
      resistance plasmid pHS-Tet from Haemophilus parasuis and the
      streptomycin/spectinomycin resistance plasmid pCCK647 from Pasteurella multocida
      in the parts coding for mobilization functions. The tet(L) gene was closely
      related to that of the Geobacillus stearothermophilus plasmid pTB19. However, the
      translational attenuator responsible for the tetracycline-inducible expression of
      tet(L) was missing in plasmid pCCK3259. A recombination site was identified
      downstream of tet(L), which might explain the integration of the tet(L) gene
      region into a basic pCCK3259 replicon. CONCLUSION: A tet(L) gene was shown for
      the first time to be responsible for tetracycline resistance in Mannheimia and
      Pasteurella isolates. This report demonstrates a lateral transfer of a
      tetracycline efflux gene in Gram-negative bovine respiratory tract pathogens,
      probably originating from Gram-positive bacteria.

PMID- 15972310
TI  - Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial
      agents.
AB  - OBJECTIVE: This study was conducted to assess the susceptibility of human
      clinical isolates of Actinomyces species to 12 antimicrobial agents. METHODS:
      Human clinical isolates of Actinomyces spp. were collected from stored
      collections held at the Microbiology Department, Edinburgh University, Anaerobe
      Reference Laboratory, Cardiff, Glasgow Dental Hospital and Glasgow Royal
      Infirmary. Each isolate was identified by restriction analysis of amplified 16S
      ribosomal DNA. MICs of 12 antibiotics comprising benzyl penicillin, amoxicillin,
      ceftriaxone, linezolid, tetracycline, deoxycycline, clindamycin, erythromycin,
      clarithromycin, ciprofloxacin, meropenem and piperacillin/tazobactam for 87
      strains of Actinomyces species were obtained by Etest methodology. RESULTS: The
      Actinomyces species identified for this study comprised: Actinomyces israelii,
      Actinomyces gerencseriae, Actinomyces turicensis, Actinomyces funkei, Actinomyces
      graevenitzii and Actinomyces europaeus. All isolates were susceptible to
      penicillin and amoxicillin. All but one strain of A. turicensis was susceptible
      to linezolid. A number of A. europaeus and A. graevenitzii isolates were
      resistant to ceftriaxone and piperacillin/tazobactam. A number of isolates of A.
      turicensis and A. europaeus also demonstrated resistance to erythromycin. All
      Actinomyces species tested appeared resistant to ciprofloxacin. CONCLUSIONS:
      Actinomyces species appear to be susceptible to a wide range of beta-lactam
      agents and these, when combined with beta-lactamase inhibitors, should be
      regarded as agents of first choice. Ciprofloxacin performed poorly. Tetracyclines
      also demonstrated poor performance. This is the first study of antimicrobial
      susceptibilities for a number of accurately identified clinical isolates of
      Actinomyces spp. There are a number of species differences in susceptibility
      profiles to the antimicrobials tested, suggesting that accurate identification
      and speciation may have an impact on clinical outcome.

PMID- 15972311
TI  - Phenotypic detection of beta-lactamase-mediated resistance to oxyimino
      cephalosporins in Enterobacteriaceae: evaluation of the Mastascan Elite Expert
      System.
AB  - OBJECTIVES: The aim of this study was to evaluate phenotypic detection of beta
      lactamase-mediated resistance to oxyimino-cephalosporins in Enterobacteriaceae
      using the Mastascan Elite Expert System challenged with a battery of
      genotypically characterized organisms. METHODS: Isolates (n = 120) were
      identified to species level and antimicrobial susceptibilities were determined
      using agar incorporation methods and Mastascan Elite. Phenotypes were examined
      using an Expert System (ES) and putative genotypes were suggested using
      interpretative reading. RESULTS: Identification was correct in 119 of 120
      isolates. The ES was able to identify the correct beta-lactam phenotype (as
      deduced from molecular methods) in a single choice in 98 of 120 (81.7%) isolates.
      In an additional 15 (12.5%) cases, the ES identified the correct beta-lactam
      phenotype within two or more choices. The detected phenotype was incorrect in
      seven (5.8%) isolates, but three of these were not inherent to the ES.
      CONCLUSIONS: The Mastascan Elite ES is relatively inexpensive and flexible and
      can identify the mechanism of resistance to oxyimino-cephalosporins in the
      majority of Enterobacteriaceae without recourse to molecular methods.

PMID- 15972312
TI  - Telavancin: in vitro activity against staphylococci in a biofilm model.
AB  - OBJECTIVES: To assess the in vitro activity of the novel lipoglycopeptide
      telavancin against staphylococcal biofilms using an in vitro pharmacokinetic
      model. METHODS: Using the Sorbarod model, biofilms were established. The strains
      tested included methicillin-susceptible and -resistant strains of Staphylococcus
      aureus and coagulase-negative staphylococci, as well as glycopeptide-intermediate
      S. aureus (GISA). The biofilms were exposed to exponentially decreasing
      concentrations of telavancin and four comparator antibiotics, vancomycin,
      teicoplanin, linezolid and moxifloxacin and the bactericidal activity of the
      antibiotics was assessed. The concentrations of the antibiotics used in these
      experiments corresponded to peak serum levels achievable in humans and the rates
      at which drug concentrations were decreased corresponded to their elimination
      half-lives. RESULTS: All of the drugs tested produced a reduction in the number
      of bacteria eluted from the biofilms. Telavancin was more effective than the
      commercially available glycopeptides, vancomycin and teicoplanin, and of the
      three, was the most active agent against both the non-GISA and GISA strains. Of
      all the antibiotics tested, moxifloxacin produced the greatest reduction in
      biofilm cells, but only against the non-GISA strains. CONCLUSIONS: Telavancin
      exhibited substantial antimicrobial activity against staphylococcal biofilms,
      including GISA strains. This study supports the case for the evaluation of
      telavancin in the treatment of staphylococcal biofilm-associated infections.

PMID- 15972313
TI  - Increase in penicillin resistance of invasive Streptococcus pneumoniae in Brazil
      after 1999.

PMID- 15972314
TI  - Sequence variation in mitochondrial complex I genes: mutation or polymorphism?
AB  - BACKGROUND: Defects of the mitochondrial genome are recognised as common causes
      of genetic disease. Sequencing of large portions or even the entire mitochondrial
      genome is routine in many laboratories for the investigation of mitochondrial
      disease. However, establishing whether a detected sequence change is polymorphic
      or pathogenic is still a major difficulty because of its highly polymorphic
      nature. This has major implications for the patient and the family. OBJECTIVE: To
      describe a scoring system for determining the likelihood that a given sequence
      variant in one of the seven mitochondrially encoded complex I (MTND) genes is
      truly pathogenic. RESULTS: The scoring system was applied to 50 reported MTND
      mutations. Using this system, 21 of the mutations analysed fell into the group of
      neutral sequence variants, 10 were classified as possibly pathogenic, three as
      probably pathogenic, and 16 as almost certainly pathogenic. CONCLUSIONS: The
      proposed scoring system should advance the interpretation of sequence variants
      and ensure that candidate pathogenic mutations are rigorously investigated.

PMID- 15972315
TI  - Characterization of Arabidopsis thaliana SMC1 and SMC3: evidence that AtSMC3 may
      function beyond chromosome cohesion.
AB  - Structural maintenance of chromosome (SMC) proteins are conserved in most
      prokaryotes and all eukaryotes examined. SMC proteins participate in many
      different aspects of chromosome folding and dynamics. They play essential roles
      in complexes that are responsible for sister chromatid cohesion, chromosome
      condensation and DNA repair. As part of studies to better understand SMC proteins
      and sister chromatid cohesion in plants we have characterized Arabidopsis SMC1
      and SMC3. Although transcripts for AtSMC1 and AtSMC3 are present throughout the
      plant, transcript levels for the two genes vary between different tissues. Cell
      fractionation and immunolocalization results showed that AtSMC3 was present in
      the nucleus and cytoplasm. In the nucleus, it is primarily associated with the
      nuclear matrix during interphase and with chromatin from prophase through
      anaphase in both somatic and meiotic cells. During mitosis and meiosis the
      protein also co-localized with the spindle from metaphase to telophase. The
      distribution of AtSMC3 in syn1 mutant plants indicated that SYN1 is required for
      the proper binding of AtSMC3 to meiotic chromosomes, but not the spindle. Data
      presented here represent the first detailed cytological study of a plant SMC
      protein and suggest that SMC3 may have multiple functions in plants.

PMID- 15972316
TI  - A unique lysophospholipid acyltransferase (LPAT) antagonist, CI-976, affects
      secretory and endocytic membrane trafficking pathways.
AB  - Previous studies have shown that inhibition of a Golgi-complex-associated
      lysophospholipid acyltransferase (LPAT) activity by the drug CI-976 stimulates
      Golgi tubule formation and subsequent redistribution of resident Golgi proteins
      to the endoplasmic reticulum (ER). Here, we show that CI-976 stimulates tubule
      formation from all subcompartments of the Golgi complex, and often these tubules
      formed independently, i.e. individual tubules usually did not contain markers
      from different subcompartments. Whereas the cis, medial and trans Golgi membranes
      redistributed to the ER, the trans Golgi network (TGN) collapsed back to a
      compact juxtanuclear position similar to that seen with brefeldin A (BFA)
      treatment. Also similar to BFA, CI-976 induced the formation of endosome tubules,
      but unlike BFA, these tubules did not fuse with TGN tubules. Finally, CI-976
      produced an apparently irreversible block in the endocytic recycling pathway of
      transferrin (Tf) and Tf receptors (TfRs) but had no direct effect on Tf uptake
      from the cell surface. Tf and TfRs accumulated in centrally located, Rab11
      positive vesicles indicating that CI-976 inhibits export of cargo from the
      central endocytic recycling compartment. These results, together with previous
      studies, demonstrate that CI-976 inhibits multiple membrane trafficking steps,
      including ones found in the endocytic and secretory pathways, and imply a wider
      role for lysophospholipid acyltransferases in membrane trafficking.

PMID- 15972317
TI  - Germ cells and fatty acids induce translocation of CD36 scavenger receptor to the
      plasma membrane of Sertoli cells.
AB  - The CD36 scavenger receptor is involved in the uptake and transport of fatty
      acids, as well as the phagocytosis process in macrophages. We show here that the
      CD36 protein is expressed by Sertoli cells in the seminiferous epithelium, mainly
      during the stages where phagocytosis takes place. Using a Sertoli-derived cell
      line, we show that addition of germ cells and residual bodies triggers a re
      localization of CD36 from the cytoplasm to the plasma membrane of the cells,
      while latex beads do not. Moreover, Sertoli cell phagocytosis of germ cells, but
      not of latex beads, is reduced by the presence of fatty acids in the culture
      medium. In the testis, CD36 plays a key role in both phagocytosis and lipid
      recycling, for constant production of mature spermatozoa.

PMID- 15972318
TI  - Acute pancreatitis during haemodialysis.

PMID- 15972320
TI  - Pseudohyperchloraemia due to bromvalerylurea abuse.

PMID- 15972319
TI  - Hypertonic glucose-based peritoneal dialysate is associated with higher blood
      pressure and adverse haemodynamics as compared with icodextrin.
AB  - BACKGROUND: Little is known about the haemodynamic effects of continuous
      ambulatory peritoneal dialysis (CAPD) despite its widespread use in the
      management of end-stage renal failure. We undertook a study to delineate the
      haemodynamic effects of CAPD using glucose-containing fluids (1.36 and 3.86%
      glucose) and icodextrin. METHODS: Eight CAPD patients were recruited for a
      prospective crossover study. Patients attended for two investigatory days (in
      random order). CAPD was carried out using 1.36% followed by 3.86% glucose
      (buffered with lactate/bicarbonate, Physioneal) on one study day and 1.36%
      glucose followed by 7.5% icodextrin (Extraneal) on the other day. Dwell times
      were 150 min. Blood pressure (BP) and a full range of haemodynamic variables
      including pulse (HR), stroke volume (SV), cardiac output (CO) and total
      peripheral resistance (TPR) were measured non-invasively using continuous
      arterial pulse wave analysis. RESULTS: BP was significantly higher during 3.86%
      glucose dwells as compared with 1.36% glucose or icodextrin dwells (P<0.0001).
      TPR during all three dwells was similar; the higher blood pressure was due to an
      increased HR, SV and, therefore, CO during 3.86% glucose dwells. The higher blood
      pressure during the 3.86% glucose dwells was present despite the highest
      ultrafiltration volume and sodium removal. CONCLUSION: This study demonstrates
      large magnitude haemodynamic changes in response to CAPD. In addition to the well
      recognized adverse effects on blood glucose and long-term peritoneal membrane
      viability, CAPD fluids containing high glucose concentrations may also exert
      undesirable effects on systemic haemodynamics, with potential long-term
      consequences for patient outcomes.

PMID- 15972321
TI  - Complications of minimal incision open nephrectomy in living donors.

PMID- 15972322
TI  - Effects of oral vitamin C supplementation on oxidative stress and inflammation
      status in haemodialysis patients.
AB  - BACKGROUND: There is increasing evidence for the presence of oxidative stress and
      vitamin C deficiency in dialysis patients. Limited data, however, are available
      regarding the effects of vitamin C supplementation on oxidative stress and
      inflammation markers in such patients. METHODS: We ran a prospective, randomized,
      open-label trial to assess the effects of oral vitamin C supplementation (250 mg
      three times per week) for 2 months on well-defined oxidative and inflammatory
      markers in 33 chronic haemodialysis (HD) patients. RESULTS: Normalization of
      plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did
      not modify plasma levels of carbonyls, C-reactive protein and albumin, or
      erythrocyte concentrations of reduced and oxidized glutathione. CONCLUSION: Short
      term oral vitamin C supplementation did not modify well-defined
      oxidative/antioxidative stress and inflammation markers in HD patients. Whether a
      higher oral dose or the intravenous route can modify these markers remains to be
      determined.

PMID- 15972323
TI  - Clinicopathological and epidemiological analysis of amyloidosis in Turkish
      patients.
AB  - BACKGROUND: The aim of the present study was to assess the correlation of
      immunohistochemical subtyping with clinical diagnosis in order to achieve useful
      epidemiological data regarding amyloidosis in Turkish patients. METHOD: We
      carried out immunohistochemical studies on 128 biopsies from various sites of 111
      patients with biopsy-proven amyloidosis and, based on the results, classified the
      patients. We assessed the correlation of immunohistochemical subtype with
      clinical diagnosis and gathered epidemiological data. RESULTS: The sites most
      biopsied were kidney and rectum, followed by the testicle, liver, small intestine
      and bladder. Amyloid deposits showed positive staining with a single antibody in
      120 biopsies. Pure amyloid A (AA) positivity was seen in 113 biopsies; six
      biopsies were positive for amyloid lambda (AL) and one for beta2-microglobulin
      (beta2MG). The clinical diagnoses of 81 patients (98 biopsies all AA positive)
      were suggestive of familial Mediterranean fever (FMF). Also AA positive were
      eight patients with tuberculosis, seven patients with rheumatoid arthritis, four
      patients with bronchiectasis and one patient with Crohn's disease. The biopsies
      from seven patients clinically suspected to have plasma cell dyscrasias were AL
      positive. One patient undergoing haemodialysis was beta2MG positive. Two patients
      without definite diagnoses showed double or triple positivity, which could not be
      interpreted and classified immunohistochemically. CONCLUSIONS: This study
      demonstrates that the predominant association of AA amyloidosis is with FMF. It
      also suggests that the routine immunohistochemical study of patients with
      amyloidosis who are of certain ethnic backgrounds suffices for classifying the
      subtype of amyloid fibril protein and the related disease.

PMID- 15972324
TI  - Attitudes of Australian pharmacists toward complementary and alternative
      medicines.
AB  - BACKGROUND: The increase in the use of complementary and alternative medicine
      (CAM) by the general public has led to increasing interest in how health
      professionals view these therapies. OBJECTIVE: To determine the knowledge and
      attitudes of pharmacists toward CAM. METHODS: An anonymous, self-administered
      questionnaire was designed and mailed to 1500 randomly selected pharmacists in
      New South Wales, Australia. RESULTS: Four hundred eighty-four responses were
      received, with 77% of respondents indicating that they had personally used CAM
      and 60% correctly identifying that CAM was comprised of more than just botanicals
      and nutritional agents. The most commonly used CAMs were herbal and vitamin
      supplements (74%), which was significantly above use of the next most frequent
      CAM, massage therapy (6%). Most pharmacists (71%) reported offering CAM products
      for sale; however, 27% of these practices did not have access to CAM information
      for pharmacy staff or patients. Pharmacists generally viewed CAM positively and
      believed that they enhanced the customers' image of pharmacy (57%), increased
      customer numbers (87%), and could increase annual sales (72%). Ninety-one percent
      of respondents believed that it is necessary for pharmacists to have knowledge of
      both CAM and conventional medicine to be able to inform patients about their
      treatment options. Books and journal articles were their primary information
      sources, with the main reasons for recommending CAM evidence of efficacy and to
      maintain general health. CONCLUSIONS: CAM use is prevalent among Australian
      pharmacists. While pharmacists are aware of their role as educators about both
      CAM and conventional medicines, there is a need for greater access to CAM
      resources and education on these therapies.

PMID- 15972325
TI  - Attitudes of pharmacists toward mental illness and providing pharmaceutical care
      to the mentally ill.
AB  - BACKGROUND: Few studies have examined the attitudes of pharmacists toward mental
      illness. OBJECTIVE: To study the attitudes of Alabama pharmacists toward both
      mental illness and the providing of pharmaceutical care to mentally ill patients.
      METHODS: The survey used in this project was composed of 3 sections. Section 1
      collected demographic information, section 2 asked 11 Likert-type questions
      concerning attitudes toward mental illness, and section 3 asked about attitudes
      toward providing pharmaceutical care to mentally ill patients. The surveys were
      distributed to pharmacists attending 3 school-sponsored continuing education
      programs. RESULTS: One hundred eighty-seven pharmacists participated in the
      survey. The vast majority (>90%) of participants disagreed or strongly disagreed
      with statements that mentally ill patients are easily recognizable,
      unintelligent, and do not care how they look. Approximately 30-50% of
      participants expressed being "more" or "much more" confident, comfortable,
      interested, and likely to perform pharmaceutical care activities for mentally ill
      patients relative to medically ill patients, while only approximately 5-20% of
      participants expressed being "less" or "much less" so. Several demographic
      factors, including gender, age, and years in practice, were associated with
      attitudes toward providing pharmaceutical care to mentally ill patients.
      CONCLUSIONS: Pharmacists expressed generally positive attitudes toward both
      mental illness and the providing of pharmaceutical care to mentally ill patients.

PMID- 15972326
TI  - Outcomes of inappropriate prescribing of beta-blockers after an acute myocardial
      infarction in a Medicaid population.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is associated with high mortality.
      beta-Blockers are known to reduce mortality and reinfarction rates when used for
      long-term prevention following an AMI. OBJECTIVE: To assess the prescribing
      patterns of beta-blockers in patients after experiencing an AMI in the West
      Virginia Medicaid program and examine its impact on patient outcomes. METHODS:
      One-year pre- and post-AMI data were extracted for 488 Medicaid patients.
      Prescribing of beta-blockers within 90 days after discharge was evaluated among
      these patients. Based on American Heart Association/American College of
      Cardiology guidelines, patients were divided into 2 groups: those prescribed
      therapy appropriately and those prescribed therapy inappropriately (underuse,
      misuse). One-year all-cause mortality, cardiac mortality, and cardiac morbidity
      were compared between the groups using survival analysis. RESULTS: Approximately
      64% of the patients were appropriately prescribed beta-blockers and illustrated
      significantly (p = 0.035) lower all-cause mortality rates compared with the
      inappropriately prescribed group at the one-year follow-up. Cardiac mortality
      evaluation showed no significant findings. The groups differed significantly in
      morbidity outcome (time to first cardiac hospitalization), with the inappropriate
      group exhibiting later hospitalization at the end of the year (p = 0.019).
      However, the appropriate group had a higher proportion of hypertensive patients,
      suggesting more severity compared with the inappropriate group. CONCLUSIONS:
      Inappropriate prescribing of beta-blockers following AMI was observed in this
      Medicaid population. Data suggest that there were overall survival benefits
      associated with appropriate beta-blocker prescribing. However, cardiac morbidity
      associated with inappropriate prescribing needs to be evaluated after adjusting
      for disease severity between the 2 groups.

PMID- 15972327
TI  - Profile of Bruce Alberts: the education president.

PMID- 15972328
TI  - The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with
      the gD N terminus and is displaced by soluble forms of viral receptors.
AB  - Entry of herpes simplex virus into the cell requires the interaction of gD with
      one of its receptors, herpesvirus entry mediator or nectin 1, and the
      intervention of gB, gH, or gL, required to execute fusion of the virion envelope
      with cell membranes. The gD ectodomain is organized in two structurally and
      functionally differentiated regions. The N terminus (residues 1-260) carries the
      receptor binding sites, and the C terminus (residues 260-310) functions as the
      pro-fusion domain (PFD), which is required for viral infectivity and fusion but
      not for receptor binding. The objective of our studies is to elucidate how gD
      links receptor recognition to the triggering of fusion. Here, we show that PFD is
      made of subdomains 1 and 2 (amino acids 260-285 and 285-310). Each one partially
      contributed to herpes simplex virus infectivity. By means of glutathione S
      transferase (GST) fusion proteins, we show that PFD bound soluble forms of gD,
      truncated at residue 260 (gD260t) or downstream. Both PFD subdomains bound
      gD260t, highlighting multiple contact sites between the N and C termini of gD.
      When gD260t was in complex with either receptor, it failed to bind GST-PFD. In
      turn, the receptors did not bind GST-PFD, irrespective of whether they were in
      complex with gD. Thus, gD260t interacted with the C terminus only if unbound to
      the receptor. We propose that (i) before receptor binding, gD adopts a "closed"
      conformation in which the N and C termini interact; and (ii) on encounter with a
      receptor, gD modifies its conformation and the N and C termini are released from
      reciprocal interactions ("opened" conformation) and enabled to trigger fusion.

PMID- 15972329
TI  - Aryl hydrocarbon receptor activation by cAMP vs. dioxin: divergent signaling
      pathways.
AB  - Even before the first vertebrates appeared on our planet, the aryl hydrocarbon
      receptor (AHR) gene was present to carry out one or more critical life functions.
      The vertebrate AHR then evolved to take on functions of detecting and responding
      to certain classes of environmental toxicants. These environmental pollutants
      include polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene), polyhalogenated
      hydrocarbons, dibenzofurans, and the most potent small-molecular-weight toxicant
      known, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). After binding of
      these ligands, the activated AHR translocates rapidly from the cytosol to the
      nucleus, where it forms a heterodimer with aryl hydrocarbon nuclear translocator,
      causing cellular responses that lead to toxicity, carcinogenesis, and
      teratogenesis. The nuclear form of the activated AHR/aryl hydrocarbon nuclear
      translocator complex is responsible for alterations in immune, endocrine,
      reproductive, developmental, cardiovascular, and central nervous system functions
      whose mechanisms remain poorly understood. Here, we show that the second
      messenger, cAMP (an endogenous mediator of hormones, neurotransmitters, and
      prostaglandins), activates the AHR, moving the receptor to the nucleus in some
      ways that are similar to and in other ways fundamentally different from AHR
      activation by dioxin. We suggest that this cAMP-mediated activation may reflect
      the true endogenous function of AHR; disruption of the cAMP-mediated activation
      by dioxin, binding chronically to the AHR for days, weeks, or months, might be
      pivotal in the mechanism of dioxin toxicity. Understanding this endogenous
      activation of the AHR by cAMP may help in developing methods to counteract the
      toxicity caused by numerous environmental and food-borne toxic chemicals that act
      via the AHR.

PMID- 15972330
TI  - NF-kappaB activation and potentiation of proinflammatory responses by the
      Helicobacter pylori CagA protein.
AB  - The Helicobacter pylori immunodominant protein, CagA, is associated with severe
      gastritis and carcinoma. Injection of CagA into gastric epithelial cells by type
      IV secretion leads to actin-cytoskeletal rearrangements and cell scattering. CagA
      has been reported to have no role in the induction of transcription factor NF
      kappaB and IL-8, which are crucial determinants for chronic inflammation. Here,
      we provide several lines of evidence showing that CagA is able to induce IL-8 in
      a time- and strain-dependent manner. We also show that by exchanging specific
      cagA genes, high IL-8-inducing H. pylori strains could be converted into low
      inducing strains and vice versa. Our results suggest that IL-8 release induced by
      CagA occurs via a Ras-->Raf-->Mek-->Erk-->NF-kappaB signaling pathway in a Shp-2-
      and c-Met-independent manner. Thus, CagA is a multifunctional protein capable of
      effecting both actin remodeling and potentiation of chemokine release.

PMID- 15972331
TI  - Triad of MR arthrographic findings in patients with cam-type femoroacetabular
      impingement.
AB  - PURPOSE: To retrospectively analyze magnetic resonance (MR) arthrographic
      findings in patients with clinical cam-type femoroacetabular impingement.
      MATERIALS AND METHODS: This study was approved by the institutional review board,
      and informed consent was waived. Study was compliant with the Health Insurance
      Portability and Accountability Act. Forty-two MR arthrograms obtained in 40
      patients with clinical femoroacetabular impingement were analyzed retrospectively
      by two radiologists. Quantitative analysis by using alpha angle measurement was
      performed to assess anterosuperior femoral head-neck morphology. Presence of
      labral tears, articular cartilage lesions, paralabral cysts, os acetabuli, and
      synovial herniation pits was recorded. Presence of the typical triad of
      anterosuperior labral tear, anterosuperior cartilage lesion, and abnormal alpha
      angle was recorded. Surgical comparison was available for 11 patients. RESULTS:
      At imaging, in 40 patients (22 male, 18 female) with a mean age of 36.5 years, 39
      of 42 hips (93%) had an abnormal alpha angle, with a mean angle of 69.7 degrees ;
      40 of 42 (95%) had an anterosuperior cartilage abnormality; and 42 of 42 (100%)
      had an anterosuperior labral tear. Thirty-seven of 42 hips (88%) had the triad.
      Six had paralabral cysts, 17 had an os acetabuli, and two had synovial herniation
      pits. Surgical comparison for 11 hips led to confirmation of all labral and
      cartilage abnormalities seen at imaging. CONCLUSION: MR arthrography demonstrated
      a triad of abnormal head-neck morphology, anterosuperior cartilage abnormality,
      and anterosuperior labral abnormality in 37 of 42 patients with cam-type
      femoroacetabular impingement.

PMID- 15972332
TI  - CT depiction of pulmonary emboli: display window settings.
AB  - PURPOSE: To compare computed tomographic (CT) window settings selected by
      radiologists with those determined by using two alternative approaches for
      depiction of pulmonary emboli (PE). MATERIALS AND METHODS: Institutional review
      board approval was obtained; informed consent was not required. This study was
      compliant with the Health Insurance Portability and Accountability Act. Twenty
      five clinical chest CT studies were obtained with a standardized PE protocol and
      retrospectively evaluated by five chest and two body CT radiologists. Of these
      studies, 13 were positive for PE, and 12 were negative. At the main pulmonary
      artery (PA), mean attenuations (MPA) and standard deviations (SDPA) were
      measured. Initially, images were displayed with a standard mediastinal window
      setting (window width, W = 400 HU; window center, C = 30 HU), and each observer
      adjusted the setting to a personally preferred setting (eg, "personal") for PE
      detection. Images displayed at this setting were compared in a side-by-side
      fashion with the "modified" (W = MPA + 2 . SDPA, C = W/2) and "double-half" (W =
      2 . MPA, C = MPA/2) window setting. Each observer rated images from 1 (ie, most
      preferred) to 3 (ie, least preferred). For quantitative analysis, window width
      and center value of each setting were divided by corresponding MPA to compute a
      width ratio and a center ratio. Window settings and ratings were compared with
      repeated-measures analysis of variance, paired t tests, and Wilcoxon signed-rank
      tests. RESULTS: Ratings for all three types of window settings were significantly
      different (P < .001). Observers preferred their personal settings the most and
      the modified settings the least. Mean ratios for the seven observers were 1.68 +/
      0.20 for window width and 0.47 +/- 0.08 for window center. Window width ratios
      for all settings were significantly different from each other (P < .001). Window
      center ratios were significantly higher for the modified setting than for the
      double-half setting (P = .013). Values for mean PA attenuation were correlated
      with window width ratios for six (86%) observers (mean r2 value = 0.29 +/- 0.19,
      P < or = .03) and with window center ratios for four (57%) observers (mean r2
      value = 0.16 +/- 0.14, P < or = .02), thus indicating a trend of setting window
      width and window center higher when contrast enhancement is lower and vice versa.
      CONCLUSION: On average, observers selected CT window settings for PE detection at
      a window width of slightly less than twice the mean PA attenuation and at a
      window center of about half the mean PA attenuation. Observers tended to use
      larger window widths and centers as the degree of PA enhancement was lower.

PMID- 15972333
TI  - Late defect on delayed contrast-enhanced multi-detector row CT scans in the
      prediction of SPECT infarct size after reperfused acute myocardial infarction:
      initial experience.
AB  - PURPOSE: To prospectively assess the accuracy of multi-detector row computed
      tomography (CT) in the prediction of infarct size after successful reperfusion of
      acute myocardial infarction (MI) by using single photon emission computed
      tomography (SPECT) images obtained 6 weeks later as the reference standard.
      MATERIALS AND METHODS: Institutional review board approval and informed consent
      were obtained. A total of 34 patients (29 men and five women; mean age, 56 years
      +/- 13) underwent dual-phase 16-detector row CT within 3 days +/- 3 after
      successful reperfusion of acute MI. Iodinated contrast medium (1.5 mL per
      kilogram of body weight) was injected at a flow rate of 3.5 mL/sec. A first
      arterial phase acquisition was followed 5 minutes later by a late acquisition,
      without reinjection of contrast medium. A radiologist and a cardiologist used a
      17-segment model in a blind analysis of images obtained during late acquisition.
      For each segment, presence of late defect or late enhancement was recorded.
      Findings were compared with SPECT studies analyzed by a nuclear medicine
      physician and a cardiologist 6 weeks after the acute event. CT defects were
      compared with SPECT defects on a segmental and per-patient basis. Mean number of
      segments with late defects on multi-detector row CT scans was compared with
      infarct size on SPECT images by using the t test. RESULTS: All patients had late
      enhancement in the infarcted myocardium. In 27 of 34 patients, a late defect
      surrounded by a subepicardial late enhancement was detected. Segments with late
      defect on CT scans were predictive of residual perfusion defects at 6-week follow
      up, with sensitivity of 78%, specificity of 91%, and accuracy of 90%. On a per
      patient basis, sensitivity was 93%, specificity was 100%, and accuracy was 94%.
      Mean number of segments with late defects on multi-detector row CT scans (ie, 3.1
      segments) was not significantly different from infarct size on SPECT images (eg,
      2.5 segments) (P = .2). CONCLUSION: Late defect on multi-detector row CT scans
      indicates residual perfusion SPECT defect and infarct size after successfully
      reperfused MI, with sensitivity of 93%, specificity of 100%, and accuracy of 94%.

PMID- 15972334
TI  - Normal anterior spinal arteries within the cervical region: high-spatial
      resolution contrast-enhanced three-dimensional MR angiography.
AB  - PURPOSE: To determine retrospectively whether the anterior spinal artery (ASA) is
      visualized in the cervical region with contrast material-enhanced high-spatial
      resolution three-dimensional magnetic resonance (MR) angiography of the
      extracranial carotid and vertebral arteries. MATERIALS AND METHODS: The
      institutional research ethics committee approved this study and provided a waiver
      for informed consent. Data sets were evaluated in 50 consecutive patients
      referred for contrast-enhanced three-dimensional MR angiography of the carotid
      arteries (32 male and 18 female patients; age range, 15-80 years; mean age, 59
      years). The ASA was defined as a linear area of high signal intensity that is
      seen anterior to the spinal cord in an arterial phase of enhancement and connects
      directly to a known arterial structure. If the linear area of high signal
      intensity was seen in the arterial phase but did not connect to a known arterial
      structure, it was considered a probable ASA. Venous enhancement was graded on a
      five-point scale (0-4) with grade 0 (no venous enhancement) or grade 1 (trace
      venous enhancement) considered to be in the arterial phase. RESULTS: The ASA was
      identified with certainty in 37 of 50 patients. A vessel visualized anterior to
      the spinal cord, which probably represented the ASA, was seen in another 11 of 50
      patients. In 29 of 50 patients the vessel was visualized only on the full-volume
      maximum intensity projection (MIP) image. In the remainder of cases the artery
      was identified on operator-defined subvolume MIP images. Continuity between the
      vessel and the vertebrobasilar arterial structures was identified in 35 of 50
      patients. The vessel was seen as a continuous structure throughout its length in
      34 patients and appeared discontinuous in 14. Radiculomedullary feeders were
      identified in 24 of 50 patients. CONCLUSION: The normal cervical ASA was
      visualized in 48 of 50 of subjects with contrast-enhanced high-spatial-resolution
      three-dimensional MR angiography.

PMID- 15972335
TI  - Prostate cancer: correlation of MR imaging and MR spectroscopy with pathologic
      findings after radiation therapy-initial experience.
AB  - PURPOSE: To prospectively evaluate magnetic resonance (MR) imaging and MR
      spectroscopy for depiction of local prostate cancer recurrence after external
      beam radiation therapy, with step-section pathologic findings as the standard of
      reference. MATERIALS AND METHODS: Study received institutional approval, and
      written informed consent was obtained. Study was compliant with Health Insurance
      Portability and Accountability Act. Sextant biopsy, digital rectal examination,
      MR imaging, MR spectroscopy, and salvage radical prostatectomy with step-section
      pathologic examination were performed in nine patients with increasing prostate
      specific antigen levels after external-beam radiation therapy. MR imaging
      criterion for tumor was a focal nodular region of reduced signal intensity at T2
      weighted imaging. MR spectroscopic criteria for tumor were voxels with choline
      (Cho) plus creatine (Cr) to citrate (Cit) ratio ([Cho + Cr]/Cit) of at least 0.5
      or voxels with detectable Cho and no Cit in the peripheral zone. Sensitivity and
      specificity of sextant biopsy, digital rectal examination, MR imaging, and MR
      spectroscopy were determined by using a prostate sextant as the unit of analysis.
      For feature analysis, MR imaging and MR spectroscopic findings were correlated
      with step-section pathologic findings. RESULTS: MR imaging and MR spectroscopy
      showed estimated sensitivities of 68% and 77%, respectively, while sensitivities
      of biopsy and digital rectal examination were 48% and 16%, respectively. MR
      spectroscopy appears to be less specific (78%) than the other three tests, each
      of which had a specificity higher than 90%. MR spectroscopic feature analysis
      showed that a metabolically altered benign gland could be falsely identified as
      tumor by using MR spectroscopic criteria; further analysis of MR spectroscopic
      features did not lead to improved MR spectroscopic criteria for recurrent tumor.
      CONCLUSION: In summary, MR imaging and MR spectroscopy may be more sensitive than
      sextant biopsy and digital rectal examination for sextant localization of cancer
      recurrence after external-beam radiation therapy.

PMID- 15972336
TI  - Multi-institutional analysis of computed and direct radiography: part II.
      Economic analysis.
AB  - PURPOSE: To compare economic aspects of equipment configurations, productivity
      levels, and patient waiting times in the performance of computed radiography (CR)
      and direct radiography (DR). MATERIALS AND METHODS: The study received internal
      review board exemption status, without the need for informed patient consent.
      Data from four study sites were used to calculate the CR-DR crossover point
      (defined as the point at which the cost-effectiveness of DR equals that of CR)
      and CR-DR annual cost differentials. Analyzed variables included equipment and
      operating costs, examination volumes, and productivity. A program was developed
      to simulate patient arrival times, number of patient examinations, and patient
      waiting times on the basis of average annualized parameters for each of the four
      clinics. Sensitivity analyses were conducted to assess utilization rates and
      determine cost optimization. Utilization rates were compared with the number of
      excess long-stay CR patients (ie, patients who spent more than 30 minutes waiting
      in the radiology department prior to CR examination) and with the cost (per
      excess long-stay CR patient who waited more than 60 minutes) averted by using DR.
      RESULTS: Excess annual costs for DR over CR at the four sites ranged from $50,757
      to $75,303. At extrapolated levels of economic penalties for long waiting times,
      the crossover point at which the DR cost became justifiable was when CR capacity
      utilization rates approached or exceeded 80%. CONCLUSION: In the current practice
      environment, with capacity utilization rates well below 80%, CR is likely to be a
      more cost-effective technology for the majority of general radiography providers.

PMID- 15972337
TI  - Multi-institutional analysis of computed and direct radiography: part I.
      Technologist productivity.
AB  - PURPOSE: To assess whether it is feasible to measure and compare work-flow times
      across institutional variations, and to apply such a comparison to technologist
      productivity in the performance of general radiographic examinations with
      computed radiography (CR) and direct radiography (DR). MATERIALS AND METHODS: The
      study received internal review board exemption. Participants were informed about
      the study and willingly participated. Observational time-motion analyses were
      performed at four sites at which CR and DR are used concurrently. The time taken
      by the technologist for patient preparation, positioning, exposure, and
      postacquisition processing, and for the examination as a whole, was recorded.
      Data collected reflect unique elements at each clinical center, and no
      standardized work flow was imposed. Work-flow performance times were correlated
      with each site profile. Preliminary statistical analyses included examination of
      distributions of original and combined variables. Descriptive statistics were
      presented as means or frequencies, depending on whether the data were continuous
      or categorical. Continuous variables were compared by using the Student t test.
      Timing differences between CR and DR for each clinical center were compared, and
      all data were analyzed by using commercially available statistical software.
      RESULTS: For all four study sites, statistically significant total examination
      time differences were observed when comparing CR and DR (P < .001). The single
      step in the examination that was found to be the largest contributor to time
      difference was postacquisition processing, which accounted for 30%-100% of the
      total time difference between the two technologies. The most time-efficient sites
      were those that had in-room postacquisition processing capability and fully
      functional integration with the radiology information system. Investigators at
      two study sites compared times for two-view chest radiography only, and those at
      the other two study sites compared times for multiview general radiographic
      examinations. Only the results of two-view comparisons were reported for each
      site. CONCLUSION: Overall technologist time was significantly shorter when
      performing tasks associated with DR than when performing comparable tasks
      associated with CR, a difference that appears to result largely from technology
      configuration, staffing, and patient management.

PMID- 15972338
TI  - T-cell homing to the pancreas in autoimmune mouse models of diabetes: in vivo MR
      imaging.
AB  - PURPOSE: To evaluate the efficiency of T-cell labeling with anionic magnetic
      nanoparticles (AMNPs) and in vivo magnetic resonance (MR) imaging monitoring of T
      cell homing to the pancreas. MATERIALS AND METHODS: In vivo MR images of pancreas
      were obtained with a 7-T MR system in 12 NOD (nonobese diabetic) mice at 11 and
      20 days after injection of AMNP-loaded or unloaded T cells. Homing of loaded T
      cells in pancreatic lymph nodes was detected by the presence of a focal dark spot
      with T2* effect in a caudal area of the pancreas. Detection of loaded T cells in
      pancreatic islets was evaluated by comparison of histograms of MR signal
      intensity generated in whole pancreas in mice injected with loaded and unloaded T
      cells. Homing of loaded T cells was confirmed at transmission electronic
      microscopy (TEM). Fifty-six mice underwent all experiments. RESULTS: Focal dark
      spots with T2* effect were observed at 11 days in all three mice injected with
      loaded T cells and in none of the three mice injected with unloaded T cells. At
      20 days, a more diffuse negative enhancement of the whole pancreas was noticed in
      one mouse injected with loaded T cells than in three mice injected with unloaded
      T cells. Presence of loaded T cells was confirmed with TEM. In vitro and in vivo
      tests confirmed that survival and function were not altered by loading.
      CONCLUSION: The ability of MR imaging to depict cell homing in living organisms
      at least 20 days after cell labeling was demonstrated, opening the way of follow
      up in autoimmune diseases and cell therapy.

PMID- 15972339
TI  - Emerging strategic themes for guiding change in academic radiology departments.
AB  - Academic radiologists are faced with increasing demands on their time and energy,
      particularly in the clinical arena, where larger examination volumes and higher
      service expectations are the norm for most medical centers. These demands are
      intensified by the continuing shortage of academic radiologists. If academic
      radiology departments continue to devote most of their resources to the clinical
      mission at the expense of research and educational missions, then there are
      potentially serious adverse consequences for long-term viability of the
      profession of radiology. This dilemma represents a critical strategic problem,
      not just for academic radiology but also for the entire profession of radiology.
      In this article, the success and growth of academic radiology during the 20th
      century are framed as the result of the dogged pursuit of certain key strategic
      themes. With the concept of paradigm shift, introduced by Kuhn, several new
      strategic themes are identified that are just emerging from changes in work
      practices, organizational structure, and mind-sets in radiology departments at
      academic medical centers. One benefit of this approach is that it facilitates the
      ability of radiologists to articulate and focus on those strategic themes that
      will help academic radiology departments to adapt more rapidly and successfully
      to environmental changes during the 21st century.

PMID- 15972340
TI  - Coronary calcium measurements: effect of CT scanner type and calcium measure on
      rescan reproducibility--MESA study.
AB  - PURPOSE: To evaluate the effect of scanner type and calcium measure on the
      reproducibility of calcium measurements. MATERIALS AND METHODS: This
      investigation was approved by the institutional review boards of each study site
      and by the Institutional Review Board of the Los Angeles Biomedical Research
      Institute. Informed consent for scanning and participation was obtained from all
      participants. The study was Health Insurance Portability and Accountability Act
      compliant. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter
      observational study of 6814 participants undergoing demographic, risk factor, and
      subclinical disease evaluations. Coronary artery calcium was measured by using
      duplicate CT scans. Three study centers used electron-beam computed tomography
      (CT), and three used multi-detector row CT. Coronary artery calcium was detected
      in 3355 participants. Three calcium measurement methods-Agatston score, calcium
      volume, and interpolated volume score-were evaluated. Mean absolute differences
      between calcium measures on scans 1 and 2, excluding cases for which both scans
      had a measure of zero, was modeled by using linear regression to compare
      reproducibility between scanner types. A repeated measures analysis of variance
      test was used to compare reproducibility across calcium measures, with mean
      percentage absolute difference as the outcome measure. Rescan reproducibility in
      relation to misregistrations, noise, and motion artifacts was also examined.
      Variables were log transformed to create a more normal distribution. RESULTS:
      Concordance for presence of calcium between duplicate scans was high and similar
      for both electron-beam and multi-detector row CT (96%, kappa = 0.92). Mean
      absolute difference between calcium scores for the two scans was 15.8 for
      electron-beam and 16.9 for multi-detector row CT scanners (P = .06). Mean
      relative differences were 20.1 for Agatston score, 18.3 for calcium volume, and
      18.3 for interpolated volume score (P < .01). Reproducibility was lower for scans
      with versus those without image misregistrations or motion artifacts (P < .01 for
      both). CONCLUSION: Electron-beam and multi-detector row CT scanners have
      equivalent reproducibility for measuring coronary artery calcium. Calcium volumes
      and interpolated volume scores are slightly more reproducible than Agatston
      scores. Reproducibility is lower for scans with misregistrations or motion
      artifacts.

PMID- 15972341
TI  - Responsible conduct of radiology research: part I. The regulatory framework for
      human research.
AB  - The purpose of the articles in this series is to explain the ethical and legal
      basis for responsible conduct of radiology research. In the current article, the
      regulatory framework of human research is explained. There is no overall
      regulatory process for protecting the rights and welfare of humans participating
      in research. Instead, legal protections in the United States are an amalgam of
      regulations from multiple federal and state agencies. The key regulations are
      from the Department of Health and Human Services, the Food and Drug
      Administration, and the Federal Privacy Rule of the Health Insurance Portability
      and Accountability Act. Which of these apply in any situation depends on many
      factors, including the funding source of the research, the site of the research,
      and the items being tested. Radiologists conducting human research need to know
      which regulations apply and how to comply with them. The regulations represent a
      set of rules based on the ethical principles of respect for persons, beneficence,
      and justice. Radiologists should understand these ethical principles for
      situations when the regulations are silent, ambiguous, or incomplete. (c) RSNA,
      2005.

PMID- 15972342
TI  - MR imaging findings in hands in early rheumatoid arthritis: comparison with those
      in systemic lupus erythematosus and primary Sjogren syndrome.
AB  - PURPOSE: To evaluate prospectively the use of magnetic resonance (MR) imaging for
      differentiating true rheumatoid arthritis (RA) from systemic lupus erythematosus
      (SLE) or primary Sjogren syndrome in patients who have inflammatory
      polyarthralgia of the hands but no radiographic evidence of RA. MATERIALS AND
      METHODS: This study had institutional review board approval, and patient informed
      consent was obtained. Twenty-eight patients (16 female and 12 male patients; mean
      age, 42 years) with early RA and 19 patients (18 female and one male patient;
      mean age, 46 years) with SLE (n = 14) or primary Sjogren syndrome (n = 5)
      underwent MR imaging of both hands. All patients had inflammatory polyarthralgia
      of the hands and no evidence of erosive changes on radiographs. Coronal T2
      weighted short inversion time inversion-recovery, transverse T1-weighted spin
      echo, transverse fat-suppressed gadolinium-enhanced T1-weighted spin-echo, and
      transverse gadolinium-enhanced three-dimensional gradient-echo MR images were
      obtained. The following MR imaging variables were assessed in the wrist and
      nonthumb metacarpophalangeal joints: synovitis, bone lesions (erosion, defect,
      and edema), and tenosynovitis. Synovitis and bone lesions were scored with the
      OMERACT RA-MRI scoring system. Findings in patients with RA and those without RA
      were compared by means of Mann-Whitney, chi2, and Fisher exact tests. RESULTS:
      The only significant difference between the two groups in terms of individual
      scores for synovitis, bone lesions, and tenosynovitis was the more frequent
      presence of tenosynovitis of the right fourth extensor tendon in patients without
      RA (P = .04). There were no significant differences between patients with RA and
      those without RA in terms of global scores for synovitis, bone lesions, and
      tenosynovitis. However, bone marrow edema in the metacarpophalangeal joints was
      seen more frequently in patients with RA (P < .001). CONCLUSION: It may be
      impossible to distinguish between patients with early RA and those without RA
      (ie, those with SLE or primary Sjogren syndrome) by means of MR imaging.

PMID- 15972343
TI  - Oxygen-enhanced MR imaging: correlation with postsurgical lung function in
      patients with lung cancer.
AB  - PURPOSE: To prospectively determine if lung function as assessed with oxygen
      enhanced magnetic resonance (MR) imaging correlates with postsurgical lung
      function in patients with lung cancer, as compared with quantitative and
      qualitative findings of computed tomography (CT) and scintigraphy. MATERIALS AND
      METHODS: Study received institutional review board approval, and informed patient
      consent was obtained. Thirty consecutive patients (16 men and 14 women, aged 44
      81 years; mean age, 65 years) considered candidates for lung resection underwent
      oxygen-enhanced MR imaging, CT, perfusion scintigraphy, and measurement of forced
      expiratory volume in 1 second (FEV1). A respiratory-synchronized inversion
      recovery half-Fourier single-shot turbo spin-echo MR sequence was used for data
      acquisition. Correlation of postsurgical lung function (postsurgical FEV1) as
      determined with oxygen-enhanced MR imaging (FEV1MR), quantitative assessment with
      CT (FEV1Quant), qualitative assessment with CT (FEV1Qual), and perfusion
      scintigraphy (FEV1PS) was conducted with actual postsurgical FEV1, and the limits
      of agreement of each were determined with Bland-Altman analysis. RESULTS:
      Correlation between postsurgical FEV1MR and actual postsurgical FEV1 values was
      excellent (r2= 0.81, P < .001); it was better than that of FEV1Qual (r2= 0.76)
      and FEV1PS (r2= 0.77) and similar to that of FEV1Quant (r2= 0.81) values. The
      limits of agreement of FEV1MR were between -9.9% and 10.9%. CONCLUSION: Oxygen
      enhanced MR imaging can be used to predict posturgical lung function in patients
      with lung cancer, similar to quantitative CT.

PMID- 15972344
TI  - Scleroderma and failed response to alefacept.

PMID- 15972345
TI  - Long-term NSAID use in primary care: changes over a decade and NICE risk factors
      for gastrointestinal adverse events.
AB  - OBJECTIVES: To examine prescribing of non-steroidal anti-inflammatory drugs
      (NSAIDs) in general practice and to compare the results with a 1993 study. To
      assess numbers at risk of gastrointestinal adverse events using the National
      Institute for Clinical Excellence (NICE) guidance on the use of cyclo-oxygenase
      (Cox) II selective drugs. METHODS: Patients currently prescribed a NSAID for 2
      months or more were identified from practice records. Demographic information,
      indications, previous gastrointestinal disease, serious co-morbidity and
      concomitant prescriptions were recorded. Data were compared with the 1993 survey
      and the NICE guidance. RESULTS: Seven thousand nine hundred and fifty-eight
      patients were registered with the practice in 2003. Two hundred and four patients
      were receiving repeat prescriptions for conventional NSAIDs and 63 for Cox II
      selective drugs. As in 1993 diclofenac (38%) and ibuprofen (24%) were the
      commonest individual agents and the main indication was regional pain. Seventy
      three per cent of patients prescribed Cox II selective drugs and 64% of patients
      prescribed conventional NSAIDs had at least one NICE risk factor for
      gastrointestinal adverse events. Frequency of co-prescription of aspirin or
      antacids was similar for conventional NSAIDs and Cox II selective drugs, but
      prescription of antacids was higher with NICE risk factors. CONCLUSION: The
      indications for NSAIDs have not changed since 1993. Cox II selective drug
      prescribing was within the NICE guidance but a substantial proportion of patients
      taking other NSAIDs had risk factors for gastrointestinal adverse events.
      Discussion with the GPs highlighted the difficulties of balancing perceived risk
      of gastrointestinal adverse events with cardioprotection and further guidance is
      urgently needed.

PMID- 15972347
TI  - Efficacy of alendronate in the treatment of avascular necrosis of the hip.

PMID- 15972349
TI  - Predictors of medication adherence in people with rheumatoid arthritis: studies
      are necessary but non-validated measures of medication adherence are of concern.

PMID- 15972350
TI  - Rupture of the splenic arterial aneurysm due to Behcet's disease.

PMID- 15972351
TI  - Interstitial lung disease in patients with polymyositis, dermatomyositis and
      amyopathic dermatomyositis.
AB  - OBJECTIVE: To assess the prevalence, characteristics and prognostic factors of
      interstitial lung disease (ILD) in Korean patients with polymyositis (PM),
      dermatomyositis (DM) and amyopathic dermatomyositis (ADM). METHODS: We reviewed
      the medical records of 72 consecutive PM and DM patients, including six patients
      with ADM, who were seen at the Rheumatology Clinic of Seoul National University
      Hospital between 1984 and 2003. RESULTS: Twenty-nine PM/DM patients (40.3%)
      developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the
      presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was
      more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed
      diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with
      DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the
      29 patients, 11 (37.9%) died. The mean survival time in ILD patients was
      significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P =
      0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like
      presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital
      capacity (FVC) < or =60% (P = 0.024). CONCLUSIONS: ILD was observed in 40.3% of
      Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like
      presentation, ADM features and an initial FVC < or =60% were associated with poor
      survival in ILD.

PMID- 15972352
TI  - Onset of steroid-induced osteonecrosis in rabbits and its relationship to
      hyperlipaemia and increased free fatty acids.
AB  - OBJECTIVES: To clarify the initial onset time of osteonecrosis after the start of
      steroid treatment and its relation to the onset of abnormal lipid metabolism.
      METHODS: Animal models were prepared by administering methylprednisolone to
      rabbits using five different steroid regimens. RESULTS: A single, acute ischaemic
      event suggested by the frequency, size or number of necrotic foci within the
      proximal femur was not different among the groups. Histological evidence of
      osteonecrosis first occurred 1-2 weeks after initial steroid administration. At
      the same time there were significantly abnormal elevations in serum lipids, which
      persisted for between 1 and 2 weeks after the initial corticoid treatment.
      Triglycerides, total cholesterol and free fatty acids were markedly elevated in
      all groups; these lipid abnormalities were significantly present in the rabbits
      with osteonecrosis but not in the rabbits without osteonecrosis. CONCLUSIONS:
      This study shows that (i) osteonecrosis appears in rabbits shortly after
      corticoids are first administered, and (ii) osteonecrosis in rabbits is
      chronologically associated with the onset of hyperlipaemia and increased free
      fatty acids. This supports the occurrence of intraosseous fat embolism as a cause
      of osteonecrosis.

PMID- 15972353
TI  - Painful hypertrophic osteoarthropathy successfully treated with octreotide. The
      pathogenetic role of vascular endothelial growth factor (VEGF).

PMID- 15972354
TI  - Complement and its breakdown products in SLE.
AB  - The complement system has important protective functions in both the innate and
      the adaptive immune systems but can also, when inappropriately activated, cause
      tissue damage. Complement deficiency predisposes to infection and also to
      development of autoimmune disease, especially SLE, and complement is at the same
      time involved in the pathogenesis of this disease. In this review, various
      aspects of this dualism are discussed. An overview of activation pathways and
      activation products is given, together with a description of autoimmunity against
      complement and the potential of complement regulation in future therapeutics.

PMID- 15972355
TI  - Evaluation and cultural adaptation of a German version of the AIMS2-SF
      questionnaire (German AIMS2-SF).
AB  - OBJECTIVES: The aim of the study was to examine the validity of a translated and
      culturally adapted version of the Arthritis Impact Measurement Scales 2, Short
      Form (AIMS2-SF) in patients suffering from osteoarthritis (OA) in primary care.
      METHODS: A structured procedure was used for the translation and cultural
      adaptation of the AIMS2-SF into German. The questionnaire was administered to 220
      primary care patients with OA of the knee or hip. Test-retest reliability was
      tested in 35 randomly selected patients, who received the questionnaire a second
      time after 1 week. The physical scale of the original AIMS2-SF was divided into
      an 'upper body limitations' scale and a 'lower body limitations' scale. RESULTS:
      With values ranging from 0.52 to 0.97 for Pearson's r, item-scale correlations
      were reasonably good. The discriminative power of separate scales was also good,
      reflected in low values for correlation between different scales, indicating
      little redundancy. Only two items (13 and 15) referring to the symptom scale
      showed item-scale correlation of r = 0.72 and r = 0.67, respectively with the
      lower body limitation scale. The assessment of internal consistency reliability
      also revealed satisfactory values: Cronbach's alpha was > or =0.83 for all
      scales, except for the social interaction scale (0.66). The test-retest
      reliability, estimated as the intraclass correlation coefficient (ICC), exceeded
      0.85 except for the affect scale (0.72). Substantial floor effects occurred in
      the upper limb scale (33.8%). Principal factor analysis confirmed the postulated
      three-factor structure with physical, physiological and social dimensions,
      explaining 49.8, 14.1 and 6.4% of the variation, respectively. The assessment of
      external validity revealed satisfactory correlations with the corresponding WOMAC
      (Western Ontario and McMaster Universities Arthrosis Index) scales. As expected,
      correlations with radiological grading were moderate to low. The correlation with
      the physician's assessment was high in the scales that were dominated by physical
      factors, but rather low in the areas of health, which were found to be dominated
      by psychological or social factors. CONCLUSION: The German AIMS2-SF is a reliable
      and valid instrument to assess the quality of life in primary care patients
      suffering from OA. When addressing the different impacts of OA, the physical
      scale should be divided into an upper body scale and a lower body scale. The
      floor and ceiling effects revealed are in accordance with the disease
      characteristics of the study sample and do not limit the significance of the
      questionnaire.

PMID- 15972356
TI  - Molecular imaging: novel tools in visualizing rheumatoid arthritis.
AB  - Molecular imaging is a rapidly emerging field in biomedical research, aiming at
      the visualization, characterization and quantification of molecular and cellular
      processes non-invasively within intact living organisms. To sense biological
      processes such as gene expression, angiogenesis, apoptosis or cell trafficking in
      vivo, imaging reporter agents that interact specifically with molecular targets
      and appropriate imaging systems are currently under development. In rheumatoid
      arthritis, these novel tools will be used to evaluate physiological and
      pathophysiological processes, to facilitate diagnosis and monitor therapeutic
      regimens, to enable reliable prognosis and to support the development of new
      therapies. In this review, we summarize the basic principles of molecular
      imaging, such as the development of molecular imaging agents, the actual
      capabilities of different imaging modalities and the most recent advances in
      molecular imaging, demonstrating the potential of this technology. With regard to
      their applicability in rheumatic diseases, we discuss potential molecular
      targets, current experimental approaches and the future prospects for molecular
      imaging in rheumatoid arthritis.

PMID- 15972357
TI  - What factors influence functional ability in patients with rheumatoid arthritis.
      Do they alter over time?
AB  - OBJECTIVES: To describe the changes in functional ability (FA) taking place over
      5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti
      rheumatic drug (DMARD) therapy, to investigate the factors having most influence
      upon FA and to compare these factors at baseline and after 5 yr of treatment.
      METHODS: Three hundred and sixty-six patients with active RA were studied as part
      of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health
      Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression
      was used to identify factors affecting FA at baseline and at 5 yr. The
      independent variables used were age, sex, visual analogue scale (VAS) pain,
      Ritchie articular index, C-reactive protein (CRP), Larsen score and log
      transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at
      baseline, improved by 21% at 1 yr and gradually returned towards baseline levels
      by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the
      most significant explanatory variables were the Ritchie articular index and CRP.
      At 5 yr the variance explained was 60%. The Ritchie articular index remained the
      strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS:
      Improvement in function did occur after commencement of the first DMARD therapy
      but was not maintained to 5 yr. The most consistent factor affecting function was
      joint tenderness. Global pain and duration of EMS were of lesser importance.
      Disease activity measures such as the CRP exerted an influence in the earlier,
      more active stages of disease: radiographic damage assumed greater importance as
      the arthritis progressed.

PMID- 15972358
TI  - Microdosimetry of radon progeny alpha particles in bronchial airway bifurcations.
AB  - A Monte Carlo code, initially developed for the calculation of microdosimetric
      spectra for alpha particles in cylindrical airways, has been extended to allow
      the computation of microdosimetric parameters for multiple source-target
      configurations in bronchial airway bifurcations. The objective of the present
      study was to investigate the effects of uniform and non-uniform radon progeny
      surface activity distributions in symmetric and asymmetric bronchial airway
      bifurcations on absorbed dose, hit frequency, lineal energy, single hit specific
      energy and LET spectra. In order to assess the effects of multiple hits, dose
      dependent specific energy spectra were calculated by solving the compound Poisson
      process by iterative convolution. While the simulations showed significant
      differences of cellular dose quantities at different cell locations for uniformly
      distributed surface activities, even higher variations, as high as several orders
      of magnitude, were observed for non-uniform surface activity distributions,
      depending on the location of the cell and the local activity distribution.

PMID- 15972359
TI  - PIN silicon diode fast neutron detector.
AB  - Two batches of diodes, with different structural ratios (the ratio of area and
      thickness), were made using different manufacturing processes. The energy
      response of the first batch to 15 kinds of monoenergetic neutrons ranging from
      180 keV to 17.56 MeV was tested, and the neutron source response of both batches
      to 239Pu-Be neutron source was measured. The energy deposition in the diodes
      irradiated by 1 keV to 20 MeV monoenergetic neutrons was calculated with
      simulation procedure. The response curve of the experimental results showed an
      approximately similar trend to that of theoretical computation. Based on the
      results of the neutron source response experiments, it was concluded that the
      response of fast neutron varied linearly with the structural ratio of the
      detectors.

PMID- 15972361
TI  - Comments on 'Are all photon radiations similar in large absorbers?--A comparison
      of electron spectra' by A.M. Kellerer and H.Roos.

PMID- 15972362
TI  - Review paper: surface modification for bioimplants: the role of laser surface
      engineering.
AB  - Often hard implants undergo detachment from the host tissue due to inadequate
      biocompatibility and poor osteointegration. Changing surface chemistry and
      physical topography of the surface influences biocompatibility. At present, the
      understanding of biocompatibility of both virgin and modified surfaces of
      bioimplant materials is limited and a great deal of research is being dedicated
      to this aspect. In view of this, the current review casts new light on research
      related to the surface modification of biomaterials, especially materials for
      prosthetic applications. A brief overview of the major surface modification
      techniques has been presented, followed by an in-depth discussion on laser
      surface modifications that have been explored so far along with those that hold
      tremendous potential for bioimplant applications.

PMID- 15972363
TI  - Exothermal characteristics and release of residual monomers from fiber-reinforced
      oligomer-modified acrylic bone cement.
AB  - The aim of this study is to determine the peak temperature of polymerization, the
      setting time and the release of residual monomers of a modified acrylic bone
      cement. Palacos R, a commercial bone cement, is used as the main component. The
      cement is modified by adding short glass fibers and resorbable oligomer fillers,
      and an additional cross-linking monomer. The test specimens are classified
      according to the composition of the bone cement matrix (i.e., oligomer-filler,
      glass-fiber reinforcement, and/or cross-linking monomer). The exothermal
      characteristics during autopolymerization are analyzed using a transducer
      connected with a computer. The quantities of residual monomers were analyzed from
      different test groups using high performance liquid chromatography (HPLC). The
      DeltaT value for the oligomer filler and the glass-fiber-containing acrylic bone
      cement is lower than that for the unmodified bone cement (2.1 +/- 0.8 vs. 23.5 +/
      4.2 degrees C). The addition of a cross-linking monomer, EGDMA, shortens the
      setting time of the autopolymerization of the unmodified bone cement (7.1 +/- 0.9
      min vs. 3.3 +/- 0.3 min). The quantity of the residual monomers released is
      higher in the modified bone cement than that in the unmodified cement. The cement
      that contains glass fibers and oligomer fillers has a considerably lower
      exothermal peak, whereas the total quantity of residual monomers released is
      increased.

PMID- 15972364
TI  - Quantification of anion and cation release from a range of ternary phosphate
      based glasses with fixed 45 mol% P2O5.
AB  - This article reports on the use of ion chromatography (IC) to investigate
      extensively the release profiles of both cations and anions and characterize the
      relationship between composition and degradation for a ternary-based Na(2)O-CaO
      P(2)O(5) glass system developed as biomaterials. Studies are carried out on
      glasses with the formula 45P(2)O(5)-55(xCaO-Na(2)O) in deionized water, where x =
      30, 35, and 40 mol%, using a cumulative release method, where the solution is
      changed at regular intervals. Degradation behavior is linear with time where the
      degradation rate shows an initial decrease with increasing CaO content. This rate
      then increases with a further addition of CaO. Cation release profiles follow
      similar trends to the degradation rates. Anion release profiles show a decrease
      for the PO(4) and linear polyphosphate (P(2)O(7) and P(3)O(10)) species with
      increasing CaO content. This decrease is attributed to the cross-linking of the
      Ca(2+) ions. In contrast, the cyclic P(3)O(9) anion exhibits the highest amount
      of anionic release, which demonstrates similar trends to the cations. These
      release patterns suggest that the cyclic P(3)O(9) species dominate the
      degradation rates. The proposed mode of degradation is a hydrolysis reaction,
      with the cyclic metaphosphate undergoing acid/base catalysis. The pH remains
      constant for the 30 and 35 mol% CaO glasses, and drops to about 5.5 for the 40
      mol% composition. By using a response factor, it is possible to
      semiquantitatively analyze the additional peaks observed in the chromatograms.
      Suggestions are also put forward as to the identity of some of these unidentified
      peaks.

PMID- 15972365
TI  - Thermal Characterizations of silver-containing bioactive glass-coated Sutures.
AB  - This study utilized and compared a number of thermal analysis methods to
      characterize the thermal properties of commercial sutures with and without
      antimicrobial coatings of silver-doped bioactive glass (AgBG) interlocking
      particulates. The effect of a slurry dipping technique used to coat resorbable
      Vicryl (polyglactin 910) and non-resorbable Mersilk surgical sutures with AgBG
      was investigated using conventional differential scanning calorimetry (DSC), high
      speed calorimetry (or HYPERDSC), and modulated temperature DSC (MTDSC). These
      methods were compared in terms of their ability to resolve the thermal
      transitions of the types of suture materials. Differential thermal analysis (DTA)
      and thermogravimetric analysis (TGA) were used to verify the thermal degradation
      temperatures of these materials and to quantify the AgBG coatings on the sutures.
      The use of complementary thermal analysis techniques enabled the understanding of
      the effect of the AgBG coating technique on the morphological properties of the
      sutures. The slurry dipping technique had no significant effect on the thermal
      transitions of both types of materials. The use of high speed calorimetry through
      DSC offered better resolution for the transitions that appeared to be weak
      through conventional heating regimes, and was able to separate broad double
      transitions. Furthermore, it was shown not to compromise either the melting
      temperature or the enthalpy of melting. Therefore this method allows for the
      accurate determination of thermal transitions through much shorter experimental
      times thus allowing for an increased sample throughput. The combined DTA and TGA
      indicated that a greater AgBG coating was obtained in the case of the Mersilk
      sutures.

PMID- 15972367
TI  - FDA's drug safety initiative: resolutions or more questions? Regulators defend
      past actions, future plans.

PMID- 15972366
TI  - Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell
      transition in clinically stable lung transplant recipients.
AB  - BACKGROUND: Obliterative bronchiolitis in chronic rejection of lung allografts is
      characterised by airway epithelial damage and fibrosis. The process whereby
      normal epithelium is lost and replaced by fibroblastic scar tissue is poorly
      understood, but recent findings suggest that epithelial cells can become
      fibroblasts through epithelial-mesenchymal transition (EMT). It is hypothesised
      that EMT occurs in lung allografts and plays a potential role in airway
      remodelling. METHODS: Sixteen stable lung transplant recipients underwent
      bronchoscopy with bronchoalveolar lavage (BAL), endobronchial biopsies, and
      bronchial brushings. Biopsy sections were stained for the fibroblast marker
      S100A4. Brushings were cultured on collagen, stained with anti-S100A4, and
      examined for further EMT markers including matrix metalloproteinase (MMP)
      zymographic activity and epithelial invasion through collagen coated filters.
      RESULTS: A median 15% (0-48%) of the biopsy epithelium stained for S100A4 in
      stable lung transplant recipients and MMP-7 co-localisation was observed. In non
      stimulated epithelial cultures from lung allografts, S100A4 staining was
      identified with MMP-2 and MMP-9 production and zymographic activity. MMP total
      protein and activity was increased following stimulation with transforming growth
      factor (TGF)-beta1. Non-stimulated transplant epithelial cells were invasive and
      penetration of collagen coated filters increased following TGF-beta1 stimulation.
      CONCLUSIONS: This study provides evidence of EMT markers in lung allografts of
      patients without loss of lung function. The EMT process may represent a final
      common pathway following injury in more common diseases characterised by airway
      remodelling.

PMID- 15972368
TI  - FDA's adverse-event surveillance needs improvement, advisers say.

PMID- 15972369
TI  - IOM panel reviews lessons for medication safety.

PMID- 15972370
TI  - Drug information confuses pregnant patients' health care providers.

PMID- 15972371
TI  - Influence of temperature and drug concentration on nafcillin precipitation.

PMID- 15972372
TI  - Update of directory of drug information centers.

PMID- 15972374
TI  - Hazards of colchicine.

PMID- 15972376
TI  - Low-dose aspirin: major benefits, minimal cost.

PMID- 15972377
TI  - Inhaled insulin for diabetes mellitus.
AB  - PURPOSE: Pharmacokinetic and safety data related to the use of inhaled insulin
      for the management of diabetes mellitus are discussed. The various pulmonary
      insulin delivery systems under development are also reviewed. SUMMARY: Several
      pharmaceutical companies are developing pulmonary insulin delivery systems. These
      products fall into two main groups: solution and drug powder formulations, which
      are delivered through different patented inhaler systems. Exubera, a rapid-acting
      insulin in powder form, has been studied extensively in patients with type 1 and
      type 2 diabetes mellitus. The AERx Insulin Diabetes Management System delivers a
      liquid form of human insulin. Preliminary data indicate that patients converting
      from insulin injections to this system showed higher compliance to therapy,
      demonstrated by improved glycemic control. Other pulmonary insulin delivery
      systems, including ProMaxx, AIR, Spiros, and Technosphere, are also under
      investigation. In humans, inhaled regular insulin is more rapidly absorbed than
      insulin from the subcutaneous injection site. The efficiency of inhaled insulin
      is lower than that of subcutaneous injection because pulmonary delivery of
      insulin involves some loss of drug within the inhaler or mouth during inhalation.
      A concern of many clinicians is the possibility of long-term effects from the
      intraalveolar deposition of insulin within the lung, since insulin is known to
      have growth-promoting properties. The long-term safety of these products has not
      been established. CONCLUSION: Several inhaled insulin products are under
      development. If these products receive marketing approval, the pulmonary delivery
      of insulin may offer patients with diabetes an alternative to repeated insulin
      injections.

PMID- 15972378
TI  - Role of adjuvant chemotherapy in the treatment of non-small-cell lung cancer.
AB  - PURPOSE: The role of adjuvant chemotherapy in the treatment of non-small-cell
      lung cancer (NSCLC) is described. SUMMARY: The intrinsic resistance of NSCLC
      tumors to chemotherapy necessitates the use of complete surgical resection of the
      malignant growth as the primary modality of treatment; however, only about one
      third of patients are appropriate candidates for surgical resection. While
      several cytotoxic combinations have been used to treat metastatic NSCLC, no
      single regimen is considered the standard of care. Given the poor prognosis of
      patients with NSCLC, adjuvant chemotherapy has been investigated as a treatment
      option but has not demonstrated a consistent survival benefit. Several recent
      studies have sought to clarify the role of adjuvant chemotherapy in the treatment
      of NSCLC: the Big Lung Trial, the International Adjuvant Lung Cancer Trial
      (IALT), the Adjuvant Lung Project Italy trial, and a study of the combination of
      uracil and tegafur, which is not yet available in the United States. The IALT,
      the largest trial among the four and sufficiently powered to detect a survival
      benefit, revealed a modest increase in survival. Complicating the issue is the
      financial cost of adjuvant therapy, especially in light of the small survival
      benefit gained. CONCLUSION: The use of adjuvant chemotherapy in patients with
      NSCLC can lead to a modest increase in survival. Platinum-based regimens are the
      most studied and should be considered the regimens of choice. However, further
      studies are needed to determine the optimal regimen and patient population that
      would derive the most benefit from this treatment.

PMID- 15972379
TI  - Effect of aprotinin on the frequency of postoperative atrial fibrillation or
      flutter.
AB  - PURPOSE: The relationship between adding aprotinin to standard care and the
      frequency of postoperative atrial fibrillation or flutter (POAF) in patients
      undergoing cardiothoracic surgery (CTS) with cardiopulmonary bypass (CPB) was
      studied. METHODS: This was a retrospective cohort evaluation. All patients at a
      hospital who underwent CTS with CPB between October 1999 and October 2003 and who
      received aprotinin during surgery were included in the treatment group. Control
      patients were those who did not receive aprotinin; they were matched with
      treatment group patients for age, valvular surgery, history of atrial
      fibrillation or flutter, renal dysfunction, peripheral artery disease, smoking,
      angina, diabetes mellitus, congestive heart failure, previous CTS, sex, beta
      blocker intolerance, and use of preoperative digoxin. The primary endpoint was
      POAF; secondary endpoints were perioperative transfusion use, length of stay
      (LOS), stroke, myocardial infarction, renal failure, graft occlusion, and death.
      RESULTS: A total of 438 patients (219 per group) were evaluated. The patients'
      mean age was 68 years, 67% were men, and 74% had had valvular surgery. Patients
      who received aprotinin (mean +/- S.D. dose, 2.75 million +/- 1.24 million
      kallikrein-inhibiting units) did not have a significantly lower frequency of POAF
      than control patients (28% versus 27%, respectively [p = 0.92]), nor was there a
      significant difference in secondary endpoints. CONCLUSION: Aprotinin therapy was
      not associated with a significant reduction in POAF in patients undergoing CTS
      with CPB. Perioperative transfusion use, LOS, stroke, myocardial infarction,
      renal failure, graft occlusion, and mortality also did not differ significantly
      between aprotinin and control groups.

PMID- 15972380
TI  - Accuracy of adverse-drug-event reports collected using an automated dispensing
      system.
AB  - PURPOSE: The accuracy of adverse-drug-event (ADE) reports collected using an
      automated dispensing system was evaluated. METHODS: ADE reports were collected by
      requiring nurses on five units in a tertiary care facility to select a reason for
      removing two tracer drugs (dextrose injection 50% [D50] and naloxone) from an
      automated dispensing system (Medstation 2000, Pyxis, San Diego, CA). The accuracy
      of the ADE reports during a period of 4.5 months was evaluated through
      retrospective chart review. The sensitivity, specificity, positive predictive
      value, and negative predictive value of the reports were calculated. RESULTS: A
      review of 61 D50 transactions found that the appropriate reason for removal was
      selected by nursing staff 62% of the time. Twenty-seven transactions were
      recorded as occurring due to an ADE, and 70% of these were confirmed in the
      medical record. The sensitivity and specificity of the ADE reports for D50 were
      55.9% (95% confidence interval [CI], 39.2-72.6%) and 70.4% (95% CI, 53.2-87.6%),
      respectively. A review of 32 naloxone transactions found that nurses correctly
      selected the reason for removal 88% of the time. Twenty-three transactions were
      recorded as occurring due to an ADE, and 87% of these were confirmed in the
      medical record. The sensitivity and specificity of the ADE reports for naloxone
      were 95.2% (95% CI, 86.1-104.4%) and 72.7% (95% CI, 46.4-99.1%), respectively.
      CONCLUSION: A Pyxis ADE reporting mechanism using the tracer drugs D50 and
      naloxone increased the overall reporting of ADEs.

PMID- 15972381
TI  - Compatibility of argatroban with abciximab, eptifibatide, or tirofiban during
      simulated Y-site administration.
AB  - PURPOSE: The physical and chemical compatibility of argatroban with abciximab,
      eptifibatide, or tirofiban during simulated Y-site administration was studied.
      METHODS: Test solutions of argatroban 1 mg/mL, abciximab 36 microg/mL,
      eptifibatide 2 mg/mL, and tirofiban 50 microg (as the hydrochloride salt) per
      milliliter in 5% dextrose injection (D5W) and in 0.9% sodium chloride injection
      (saline) were prepared in duplicate by using aseptic technique. Argatroban
      solution was mixed with abciximab, eptifibatide, or tirofiban solution, each at a
      ratio of 1:1 by volume, and at 4:1 with abciximab solution, 8:1 with tirofiban
      solution, and 16:1 with eptifibatide solution. Compatibility was evaluated
      immediately after solution preparation and after storage for four hours at 20-25
      degrees C. Physical compatibility was determined with the unaided eye and with a
      particle counter, and chemical compatibility was measured with high-performance
      liquid chromatography. The chemical compatibility of argatroban and abciximab was
      not tested because of the poor stability or recovery of abciximab in the test
      diluents. RESULTS: Argatroban was physically compatible with abciximab,
      eptifibatide, and tirofiban in D5W at each ratio tested and in saline at a 1:1
      ratio. Argatroban was chemically compatible with eptifibatide and tirofiban. No
      significant impurities were detected, except for a single impurity in argatroban
      eptifibatide 1:1 admixtures. CONCLUSION: At concentrations commonly used in
      practice, argatroban was physically compatible with abciximab and physically and
      chemically compatible with eptifibatide and tirofiban for four hours at 20-25
      degrees C.

PMID- 15972382
TI  - Progress of Veterans Affairs pharmacies toward goals and objectives of ASHP's
      2015 Initiative.

PMID- 15972383
TI  - Apparent anaphylaxis associated with pantoprazole.

PMID- 15972384
TI  - ASHP therapeutic position statement on the daily use of aspirin for preventing
      cardiovascular events.

PMID- 15972385
TI  - Pharmacy practice in Thailand.

PMID- 15972386
TI  - RANK ligand and TNF-alpha mediate acid-induced bone calcium efflux in vitro.
AB  - Chronic metabolic acidosis stimulates net calcium efflux from bone due to
      increased osteoclastic bone resorption and decreased osteoblastic collagen
      synthesis. Previously, we determined that incubation of neonatal mouse calvariae
      in medium simulating physiological metabolic acidosis leads to a significant,
      cyclooxygenase-dependent, increase in RNA for bone cell receptor activator of NF
      kappaB ligand (RANKL) compared with incubation in neutral pH medium. In this
      study, we tested the hypothesis that the acid-mediated increase in RANKL
      expression is a primary mechanism for the stimulated osteoclastic resorption.
      Acid medium increased the medium concentration of sRANKL without altering the
      concentration of the decoy receptor osteoprotegerin (OPG). Inhibition of the
      RANKL pathway with concentrations of OPG up to 25 ng/ml, far greater than
      physiological, did not significantly decrease the robust acid-induced Ca efflux
      from bone nor did incubation of the calvariae with a different inhibitor, RANK/Fc
      (up to 50 ng/ml). Thus acid-induced net Ca efflux appears to involve mechanisms
      in addition to the RANK/RANKL pathway. Osteoblasts also produce TNF-alpha,
      another cytokine that stimulates the maturation and activity of osteoclasts.
      Incubation of calvariae in acid medium caused a significant increase in TNF-alpha
      levels. Incubation of calvariae with anti-TNF (up to 250 ng/ml) did not
      significantly decrease acid-induced net Ca efflux. However, the combination of
      RANK/Fc plus anti-TNF caused a significant but subtotal reduction in acid-induced
      Ca efflux, whereas the combination of RANK/Fc plus an isotype-matched control for
      the anti-TNF had no effect on Ca release. Thus simultaneous inhibition of RANKL
      and TNF-alpha is necessary to reduce acid-induced, cell-mediated net Ca efflux
      from bone; however, additional osteoblast-produced factors must also be involved
      in acid-induced, cell-mediated bone resorption.

PMID- 15972387
TI  - Activation of NAD(P)H oxidase by outward movements of H+ ions in renal medullary
      thick ascending limb of Henle.
AB  - The present study was designed to test the hypothesis that the production of
      superoxide (O(2)-* by NAD(P)H oxidase is coupled to tubular metabolic activity
      through ionic activation mediated by H(+) movement across cell membrane. Using
      dual fluorescent microscopic imaging analysis, intracellular O(2)-* levels and pH
      (pH(i)) in renal medullary thick ascending limb of Henle (TALH) cells were
      simultaneously measured. It was found that intracellular O(2)-* levels in these
      cells were increased in parallel to the elevation of pH(i) by outflow of H(+)
      induced via NH(4)Cl loading followed by rapid removal. This increase in
      intracellular O(2)-* levels was substantially blocked by an inhibitor of
      Na(+)/H(+) exchanger, methylisobutyl-amiloride (MIA; 100 microM), a chemical SOD
      mimetic, Tiron (1 mM) or an inhibitor of NAD(P)H oxidase, diphenylene iodonium
      (DPI; 100 microM). In additional groups of TALHs, a proton ionophore,
      carbonylcyanide m-chlorophenylhydrazone (10 microM) was used to produce H(+)
      conductance, leading to H(+) flux across cell membrane depending on extracellular
      pH. The efflux of H(+) increased both pH(i) and intracellular O(2)-* levels, but
      the influx of H(+) did not increase intracellular O(2)-* levels. The H(+) efflux
      induced increase in intracellular O(2)-* levels was completely blocked by DPI and
      another NAD(P)H oxidase inhibitor, apocynin (100 microM). In in invo experiments,
      renal medullary infusion of MIA (100 microM) was found to significantly decrease
      the concentrations of H(2)O(2) in the renal medullary interstitium. These results
      suggest that it is the outward movements of H(+) ions that activates NAD(P)H
      oxidase to produce O(2)-* in TALH cells. This H(+) outflow-associated activation
      of NAD(P)H oxidase importantly contributes to tissue levels of reactive oxygen
      species in the renal medulla.

PMID- 15972388
TI  - PKA-dependent ENaC trafficking requires the SNARE-binding protein complexin.
AB  - Acute regulation of epithelial sodium channel (ENaC) function at the apical
      surface of polarized kidney cortical collecting duct (CCD) epithelial cells
      occurs in large part by changes in channel number, mediated by membrane vesicle
      trafficking. Several soluble N-ethyl-maleimide-sensitive factor attachment
      protein receptors (SNARE) have been implicated in this process. A novel SNARE
      binding protein, complexin, has been identified in nervous tissue which
      specifically binds to and stabilizes SNARE complexes at synaptic membranes to
      promote vesicle fusion. To test whether this protein is present in mouse CCD
      (mCCD) cells and its possible involvement in acute ENaC regulation, we cloned
      complexin (isoform II) from a mouse kidney cDNA library. Complexin II mRNA
      coexpressed with alpha-, beta-, and gamma-ENaC subunits in Xenopus laevis oocytes
      reduced sodium currents to 16 +/- 3% (n = 19) of control values. Short-circuit
      current (I(sc)) measurements on mCCD cell lines stably over- or underexpressing
      complexin produced similar results. Basal I(sc) was reduced from 12.0 +/- 1.0 (n
      = 15) to 2.0 +/- 0.4 (n = 15) and 1.8 +/- 0.3 (n = 17) microA/cm(2),
      respectively. Similarly forskolin-stimulated I(sc) was reduced from control
      values of 20.0 +/- 2 to 2.7 +/- 0.5 and 2.3 +/- 0.4 microA/cm(2) by either
      increasing or decreasing complexin expression. Surface biotinylation demonstrated
      that the complexin-induced reduction in basal I(sc)was due to a reduction in
      apical membrane-resident ENaC and the inhibition in forskolin stimulation was due
      to the lack of ENaC insertion into the apical membrane to increase surface
      channel number. Immunofluorescent localization of SNARE proteins in polarized
      mCCD epithelia detected the presence of syntaxins 1 and 3 and synaptosomal
      associated protein of 23 kDa (SNAP-23) at the apical membrane, and vesicle
      associated membrane protein (VAMP2) was localized to intracellular compartments.
      These findings identify SNAREs that may mediate ENaC-containing vesicle insertion
      in mCCD epithelia and suggest that stabilization of SNARE interactions by
      complexin is an essential aspect of the regulated trafficking events that
      increase apical membrane ENaC density either by constitutive or regulated
      trafficking pathways.

PMID- 15972389
TI  - Mechanoregulation of intracellular Ca2+ concentration is attenuated in collecting
      duct of monocilium-impaired orpk mice.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is characterized by the
      progressive dilatation of collecting ducts, the nephron segments responsible for
      the final renal regulation of sodium, potassium, acid-base, and water balance.
      Murine models of ARPKD possess mutations in genes encoding cilia-associated
      proteins, including Tg737 in orpk mice. New findings implicate defects in
      structure/function of primary cilia as central to the development of polycystic
      kidney disease. Our group (Liu W, Xu S, Woda C, Kim P, Weinbaum S, and Satlin LM,
      Am J Physiol Renal Physiol 285: F998-F1012, 2003) recently reported that
      increases in luminal flow rate in rabbit collecting ducts increase intracellular
      Ca(2+) concentration ([Ca(2+)](i)) in cells therein. We thus hypothesized that
      fluid shear acting on the apical membrane or hydrodynamic bending moments acting
      on the cilium increase renal epithelial [Ca(2+)](i). To further explore this, we
      tested whether flow-induced [Ca(2+)](i) transients in collecting ducts from
      mutant orpk mice, which possess structurally abnormal cilia, differ from those in
      controls. Isolated segments from 1- and 2-wk-old mice were microperfused in vitro
      and loaded with fura 2; [Ca(2+)](i) was measured by digital ratio fluorometry
      before and after the rate of luminal flow was increased. All collecting ducts
      responded to an increase in flow with an increase in [Ca(2+)](i), a response that
      appeared to be dependent on luminal Ca(2+) entry. However, the magnitude of the
      increase in [Ca(2+)](i) in 2- but not 1-wk-old mutant orpk animals was blunted.
      We speculate that this defect in mechano-induced Ca(2+) signaling in orpk mice
      leads to aberrant structure and function of the collecting duct in ARPKD.

PMID- 15972390
TI  - Stimulation of Na+ transport by AVP is independent of PKA phosphorylation of the
      Na-K-ATPase in collecting duct principal cells.
AB  - Arginine-vasopressin (AVP) stimulates Na(+) transport and Na-K-ATPase activity
      via cAMP-dependent PKA activation in the renal cortical collecting duct (CCD). We
      investigated the role of the Na-K-ATPase in the AVP-induced stimulation of
      transepithelial Na(+) transport using the mpkCCD(c14) cell model of mammalian
      collecting duct principal cells. AVP (10(-9) M) stimulated both the amiloride
      sensitive transepithelial Na(+) transport measured in intact cells and the
      maximal Na pump current measured by the ouabain-sensitive short-circuit current
      in apically permeabilized cells. These effects were associated with increased Na
      K-ATPase cell surface expression, measured by Western blotting after streptavidin
      precipitation of biotinylated cell surface proteins. The effects of AVP on Na
      pump current and Na-K-ATPase cell surface expression were dependent on PKA
      activity but independent of increased apical Na(+) entry. Time course experiments
      revealed that in response to AVP, the cell surface expression of both endogenous
      Na-K-ATPase and hybrid Na pumps containing a c-myc-tagged wild-type human
      alpha(1)-subunit increased transiently. Na-K-ATPase cell surface expression was
      maximal after 30 min and then declined toward baseline after 60 min.
      Immunoprecipitation experiments showed that PKA activation did not alter total
      phosphorylation levels of the endogenous Na-K-ATPase alpha-subunit. In addition,
      mutation of the PKA phosphorylation site (S943A or S943D) did not alter the time
      course of increased cell surface expression of c-myc-tagged Na-K-ATPase in
      response to AVP or to dibutyryl-cAMP. Therefore, stimulation of Na-K-ATPase cell
      surface expression by AVP is dependent on PKA but does not rely on alpha(1)
      subunit phosphorylation on serine 943 in the collecting duct principal cells.

PMID- 15972391
TI  - Correlation and regression.

PMID- 15972392
TI  - Survival analysis.

PMID- 15972394
TI  - A comprehensive portrait of teleradiology in radiology practices: results from
      the American College of Radiology's 1999 Survey.
AB  - OBJECTIVE: This article presents a comprehensive portrait of the characteristics
      of teleradiology systems of radiology practices as of 1999. Our purposes are to
      help profile a rapidly evolving area of radiology that has been underexamined to
      date and to provide a baseline with which future findings can be compared.
      MATERIALS AND METHODS: In 1999, the American College of Radiology surveyed 970
      practices by mail. A response rate of 66% was achieved. Responses were weighted
      to represent all radiology practices in the United States. Data from nine
      questions specifically designed to profile the use of teleradiology were analyzed
      using descriptive statistical methods and multivariate regression analyses.
      RESULTS: Seventy-one percent of multiradiologist practices had teleradiology
      systems in place, using them to interpret 5% of their studies. For solo
      practices, corresponding statistics were 30% and 14%. Ninety-two percent of
      multiradiologist practices with teleradiology systems used them for preliminary
      on-call interpretation. Other major uses included consultation with other
      radiologists (20%) and primary interpretation of studies (18%). Ninety-five
      percent of multiradiologist practices with teleradiology systems used them to
      interpret CT, 84% used them for sonography, 69% for nuclear medicine, 47% for
      MRI, and 43% for conventional radiographs. CONCLUSION: Teleradiology had already
      become a fixture in most practices by 1999, though it was used for only a small
      fraction of image interpretations. Its widespread presence positioned
      teleradiology to become a key element of radiology practice nationwide.

PMID- 15972395
TI  - Can a radiologist be compelled to testify as an expert witness?

PMID- 15972396
TI  - Managing risk: threat or opportunity?
AB  - OBJECTIVE: Radiologists often regard risk management as a burden or even a
      threat. This article examines some of the most important reasons every
      radiologist should regard managing risk as an opportunity. CONCLUSION: There are
      short-term risks and costs to a program of risk management, but they are far less
      than the long-range costs of inaction. More importantly, managing risk well is an
      opportunity to excel as a physician and leader.

PMID- 15972397
TI  - Reporting success rate at 12 months after percutaneous treatment for peripheral
      arterial disease: the impact of outcome criteria.
AB  - OBJECTIVE: The objectives of our study were to assess the influence of varying
      outcome criteria on the success rate at 12 months after percutaneous intervention
      for peripheral arterial disease and to suggest a reporting method that can be
      used in studies that report results of interventions as measured by parameters of
      daily clinical practice. MATERIALS AND METHODS: The outcomes of 1,411 consecutive
      procedures in 1,583 limbs recorded in a multicenter registry involving six
      hospitals were analyzed. Six sets of outcome criteria were evaluated: one based
      on symptomatic change, three based on ankle-brachial index (ABI) measurements,
      and two based on combining the symptomatic and ABI outcome measures. Agreement
      among the outcome measures was compared using the kappa statistic. RESULTS: The
      ABI outcome measures alone showed good agreement (kappa = 0.74-0.94). The
      symptomatic outcome measures yielded a substantially higher 12-month success rate
      than the ABI outcome measures (difference, 18-24%) and the agreement was only
      fair (kappa = 0.52-0.60). The agreement between symptomatic outcome and ABI
      outcome measures was poor in patients with a pretreatment ABI measurement at rest
      of more than 0.90 (kappa = 0.20). Combining symptomatic outcome and the ABI
      outcome measures with the logical operator "OR" showed good agreement with the
      symptomatic outcome measures alone (kappa = 0.97) and using "AND" showed good
      agreement with the ABI outcome measures alone (kappa = 0.87). CONCLUSION: In
      patients with a pretreatment ABI measurement at rest of more than 0.90,
      classifying procedures using a criterion based on improvement in ABI measurements
      with more than 0.10 is inaccurate and underestimates the actual success rate at
      12 months after percutaneous intervention. Furthermore, combining subjective
      improvement in symptoms and improvement in ABI measurements does not yield more
      information than reporting these outcome measures separately. Therefore, we
      suggest that improvement in symptoms and improvement in ABI measurements should
      be reported separately to indicate the 12-month success rate of percutaneous
      interventions for peripheral arterial disease.

PMID- 15972398
TI  - Percutaneous radiofrequency ablation of hepatic tumors: postablation syndrome.
AB  - OBJECTIVE: Our objective was to define the spectrum and possible predictors of
      symptoms that occur in patients after percutaneous radiofrequency ablation of
      hepatic tumors. SUBJECTS AND METHODS: We performed 50 consecutive percutaneous
      radiofrequency ablation sessions on 39 patients with a total of 89 liver tumors.
      All patients had pre- and postablation laboratory studies and CT or MRI scans.
      After treatment, patients were followed for 3 weeks with a standardized
      questionnaire to assess for postablation symptoms. Comparisons of the presence or
      absence of symptoms were made for the laboratory test values, liver volumes, and
      pre- and postablation tumor volumes. RESULTS: Postablation symptoms occurred in
      14 of 39 (36%) patients after 17 of 50 (34%) ablation sessions. Symptoms
      consisted of fever (16/17), malaise (12/17), chills (6/17), delayed pain (5/17),
      and nausea (2/17). On average, the symptoms presented 3 days after ablation and
      lasted 5 days. Statistically significant (p < 0.01) predictors of symptoms were
      tumor volumes > 50 cm3 (4.5 cm diameter), ablated tissue volumes > 150 cm3 (6.5
      cm diameter), a difference between preablation tumor volume and the volume of
      tissue ablated > 125 cm3, or postablation aspartate aminotransferase levels > 350
      IU/L. CONCLUSION: Approximately one third of patients undergoing percutaneous
      radiofrequency ablation of hepatic tumors develop delayed, transient flulike
      symptoms that can be treated conservatively and are significantly related to the
      volume of tissue ablated. Familiarity with this postablation syndrome should
      facilitate appropriate management of affected patients.

PMID- 15972399
TI  - The utility of a drainage needle for percutaneous abscess drainage.
AB  - OBJECTIVE: In this article, I describe a percutaneous drainage needle that
      consists of six side holes in its cannula. The needle is specially designed for
      effective evacuation of complex abscess collections consisting of internal solid
      components, including floating debris, that tend to block the needle aperture
      during aspiration. The characteristic features of the needle and its performance
      in both in vitro and in vivo environments are described. MATERIALS AND METHODS:
      An in vitro experiment was performed with the use of a model of a fluid
      collection containing floating sheets of gelatin sponge to mimic a complex body
      collection consisting of floating fibrinous strands. Five radiologists were asked
      to perform aspiration from two collections of normal saline and 5%
      methylcellulose of two different volumes using an ordinary aspiration needle and
      the drainage needle. The needle was evaluated in a prospective in vivo study of
      30 postoperative abdominal collections in 29 consecutive patients that were
      drained by a single radiologist. Complete evacuation was attempted initially with
      a conventional aspiration needle. When there was sonographic evidence of residual
      fluid collection, a repeat aspiration using a drainage needle was performed
      during the same session. RESULTS: In the in vitro experiment, the median
      percentage of fluid aspirated with the conventional needle from the 10- and 15-mL
      collections of saline was 10% and 15% and from the 10 mL and 15 mL of
      methylcellulose solution was 20% and 26.67%, respectively, whereas the drainage
      needle was able to remove 100% of fluid in all attempts. In the in vivo study,
      the conventional needle was able to remove all drainable fluid from the 12 simple
      collections. For the 18 complex collections, the drainage needle was always able
      to remove some residual fluid from the collection after aspiration with the
      conventional needle. The median percentage of fluid volume aspirated with the
      conventional needle was 55.6%, whereas that aspirated with both the conventional
      and drainage needles was 95.5%, with a significant difference by Wilcoxon's
      signed rank test (p < 0.001). CONCLUSION: This drainage needle was effective in
      evacuating fluid from complex abdominal collections that could not be drained
      with conventional end-hole needles.

PMID- 15972400
TI  - Radiofrequency ablation of renal cell carcinoma: part 1, Indications, results,
      and role in patient management over a 6-year period and ablation of 100 tumors.
AB  - OBJECTIVE: The objectives of our article are to review our experience with
      radiofrequency ablation of renal cell carcinoma and to assess size and location
      as predictors of the ability to achieve complete necrosis by imaging criteria.
      MATERIALS AND METHODS: Over a 6-year period, 100 renal tumors in 85 patients
      underwent radiofrequency ablation at a single institution. The absence of
      enhancement on CT or MRI after radiofrequency ablation was interpreted as
      complete coagulation necrosis. Results were analyzed by tumor size and location
      using multivariate analysis. A p value of 0.05 or less was considered
      significant. RESULTS: All 52 small (3 cm) and all 68 exophytic tumors underwent
      complete necrosis regardless of size, although many large tumors (> 3 cm)
      required a second ablation session. Using multivariate analysis, we found that
      both small size (p < 0.0001) and noncentral location (p = 0.0049) proved to be
      independent predictors of complete necrosis after a single ablation session.
      Location was a significant predictor (p = 0.015) of complete necrosis after any
      number of sessions, whereas size showed a strong trend (p = 0.059) toward
      predicting success after any number of sessions. Complications were either self
      limited or readily treated and included hemorrhage (major, n = 2; minor, n = 3),
      inflammatory track mass (n = 1), transient lumbar plexus pain (n = 2), ureteral
      injury (n = 2), and skin burns (n = 1). CONCLUSION: Radiofrequency ablation is a
      promising minimally invasive therapy for renal cell carcinoma in patients who are
      not good operative candidates. Small size and noncentral location are favorable
      tumor characteristics, although large tumors can sometimes be successfully
      treated with multiple ablation sessions.

PMID- 15972401
TI  - Radiofrequency ablation of renal cell carcinoma: part 2, Lessons learned with
      ablation of 100 tumors.
AB  - OBJECTIVE: The objective of our study was to review radiofrequency ablation of
      100 renal tumors and lessons learned with respect to electrode approach, effects
      on collecting system, bowel proximity, and patterns of residual disease.
      MATERIALS AND METHODS: Over 6 years, 100 renal tumors in 85 patients underwent
      radiofrequency ablation. Images were reviewed to determine the following: effect
      of initial electrode approach at and parallel to the tumor-kidney interface;
      effect of collecting system proximity to the tumor and to the zone of ablation;
      bowel proximity to the tumor and strategies to protect bowel; patterns of
      residual disease; and approaches at subsequent sessions. RESULTS: The initial
      placement of the electrode at and parallel to the tumor-kidney interface did not
      result in significantly fewer overlapping ablations (p = 0.91) or a lower rate of
      residual disease (p = 0.86). Direct contiguity of tumor or zone of ablation to
      the collecting system did not increase the complication rate. However,
      obscuration of calyces by a central tumor was a significant predictor of
      collecting system hemorrhage necessitating treatment (p < 0.001) seen in three of
      nine tumors obscuring calyces. Clinically significant urine leaks were rare
      (1/100) and related to downstream obstruction. There were no bowel complications
      despite the fact that 27 of the tumors were within 1 cm of bowel. Protective
      strategies progressed from reliance on electrode positioning to hydrodissection.
      Residual patterns were predominantly nodules or crescents, and straight
      electrodes were commonly used to approach residual disease. CONCLUSION: Initial
      electrode position at and parallel to the tumor-kidney interface does not result
      in less difficult or more successful ablations. Contiguity of tumor or zone of
      ablation to the collecting system does not increase the risk of complications,
      but obscuration of calyces does. Bowel complications are rare, and protection
      with hydrodissection is becoming more common. Residual tumor presents as nodules
      or crescents of persistent enhancement.

PMID- 15972402
TI  - CT-guided Kopans hookwire placement for preoperative localization of an
      appendicolith.
AB  - OBJECTIVE: Retained appendicoliths that have spilled into the peritoneal cavity
      after appendectomy may act as a nidus for recurrent abscess. Appendicoliths are
      often small and located in inaccessible recesses of the peritoneum, making
      surgical localization and removal difficult. The objective of the study was to
      facilitate surgical removal of an appendicolith using a Kopans breast
      localization hookwire placed with CT guidance. CONCLUSION: Preoperative CT-guided
      localization of small inaccessible retained appendicoliths can be readily
      performed using a Kopans hookwire.

PMID- 15972403
TI  - Pediatric return electrodes for radiofrequency ablation in children.

PMID- 15972404
TI  - Percutaneous transthoracic radiofrequency ablation of renal tumors using an
      iatrogenic pneumothorax.
AB  - OBJECTIVE: We report on a new technique for percutaneous radiofrequency ablation
      of tumors in the upper pole of kidneys in the presence of intervening lung
      parenchyma. CONCLUSION: Percutaneous radiofrequency ablation of tumors in the
      upper pole of kidneys with intervening lung parenchyma can be accomplished
      successfully using a transthoracic approach through an iatrogenic pneumothorax.
      This technique allows for precise placement and repositioning of the
      radiofrequency electrode under CT guidance without repeated puncture of the
      visceral pleura.

PMID- 15972405
TI  - Rescue TIPS in acute Budd-Chiari syndrome.

PMID- 15972406
TI  - Intrathecal gadolinium-enhanced MR myelography showing multiple dural leakages in
      a patient with Marfan syndrome.

PMID- 15972407
TI  - Diagnostic accuracy of stress first-pass contrast-enhanced myocardial perfusion
      MRI compared with stress myocardial perfusion scintigraphy.
AB  - OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of
      stress perfusion MRI acquired with saturation-recovery prepared turbo fast low
      angle shot (turbo FLASH) compared with stress myocardial perfusion scintigraphy.
      Recent studies show that first-pass contrast-enhanced myocardial perfusion MRI
      can provide noninvasive detection of low-limiting stenosis in the coronary
      artery. MATERIALS AND METHODS: First-pass contrast-enhanced MR images were
      acquired at rest and during stress in 40 patients with suspected coronary artery
      disease. All patients underwent thallium-201 SPECT without attenuation correction
      and coronary angiography. Two reviewers independently assigned one of five
      confidence grades without knowing the results of coronary angiography for
      receiver operating characteristic (ROC) analysis. Luminal stenosis >70% on
      coronary angiography was used as a reference standard. RESULTS: On coronary
      angiography, 70% or greater diameter stenosis of the coronary artery was observed
      in 21 (52.5%) of 40 patients. The areas under the ROC curve for detection of
      significant stenosis in the individual coronary artery were 0.86 (observer 1) and
      0.84 (observer 2) for MRI. These values were 0.79 (observer 1, p = not
      significant) and 0.72 (observer 2, p = not significant) for 201Tl SPECT.
      CONCLUSION: The diagnostic accuracy of stress perfusion MRI acquired with
      saturation-recovery-prepared turbo FLASH was comparable with that of stress 201Tl
      SPECT. Stress first-pass contrast-enhanced MRI is a noninvasive technique that
      can be used as an alternative to stress myocardial perfusion scintigraphy.

PMID- 15972408
TI  - Comparison of 3D segmented gradient-echo and steady-state free precession
      coronary MRI sequences in patients with coronary artery disease.
AB  - OBJECTIVE: Our objective was to compare two state-of-the-art coronary MRI (CMRI)
      sequences with regard to image quality and diagnostic accuracy for the detection
      of coronary artery disease (CAD). SUBJECTS AND METHODS: Twenty patients with
      known CAD were examined with a navigator-gated and corrected free-breathing 3D
      segmented gradient-echo (turbo field-echo) CMRI sequence and a steady-state free
      precession sequence (balanced turbo field-echo). CMRI was performed in a
      transverse plane for the left coronary artery and a double-oblique plane for the
      right coronary artery system. Subjective image quality (1- to 4-point scale, with
      1 indicating excellent quality) and objective image quality parameters were
      independently determined for both sequences. Sensitivity, specificity, and
      accuracy for the detection of significant (> or = 50% diameter) coronary artery
      stenoses were determined as defined in invasive catheter X-ray coronary
      angiography. RESULTS: Subjective image quality was superior for the balanced
      turbo field-echo approach (1.8 +/- 0.9 vs 2.3 +/- 1.0 for turbo field-echo; p <
      0.001). Vessel sharpness, signal-to-noise ratio, and contrast-to-noise ratio were
      all superior for the balanced turbo field-echo approach (p < 0.01 for signal-to
      noise ratio and contrast-to-noise ratio). Of the 103 segments, 18% of turbo field
      echo segments and 9% of balanced turbo field-echo segments had to be excluded
      from disease evaluation because of insufficient image quality. Sensitivity,
      specificity, and accuracy for the detection of significant coronary artery
      stenoses in the evaluated segments were 92%, 67%, 85%, respectively, for turbo
      field-echo and 82%, 82%, 81%, respectively, for balanced turbo field-echo.
      CONCLUSION: Balanced turbo field-echo offers improved image quality with
      significantly fewer nondiagnostic segments when compared with turbo field-echo.
      For the detection of CAD, both sequences showed comparable accuracy for the
      visualized segments.

PMID- 15972409
TI  - Effectiveness of delayed enhanced MRI for identification of cardiac sarcoidosis:
      comparison with radionuclide imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of delayed
      enhanced MRI for detecting cardiac sarcoidosis and to clarify the relationship
      between the findings of MRI and those of radionuclide imaging. CONCLUSION:
      Delayed enhanced MRI is considered a useful method for the early identification
      of cardiac sarcoidosis. Delayed hyperenhancement is frequently associated with a
      reduction of regional wall motion and thallium-201 perfusion defects.

PMID- 15972410
TI  - Bronchogenic cyst in the left atrium combined with persistent left superior vena
      cava: the first case in the literature.

PMID- 15972411
TI  - CT findings of surgically resected pleomorphic carcinoma of the lung in 30
      patients.
AB  - OBJECTIVE: The objective of our study was to assess the CT features of surgically
      resected pleomorphic carcinoma of the lung. CONCLUSION: The CT features of
      pleomorphic carcinoma of the lung appear to be dictated by the epithelial
      component of the tumor. Among the various subtypes of pleomorphic carcinoma, the
      large cell and giant cell subtype showed constant CT features including
      subpleural location, peritumoral areas of ground-glass attenuation, and extensive
      central low-attenuation areas.

PMID- 15972412
TI  - Lung cancer screening experience: a retrospective review of PET in 22 non-small
      cell lung carcinomas detected on screening chest CT in a high-risk population.
AB  - OBJECTIVE: The objective of our study was to retrospectively review the PET
      results of non-small cell lung carcinomas detected on screening chest CT in a
      high-risk population. CONCLUSION: PET findings were negative in 32% of the cases
      of non-small cell carcinomas that were detected on screening CT in a high-risk
      patient population. These tumors were small, low-grade, or both. The most common
      histology was bronchioloalveolar cell carcinoma. The role of PET in evaluating
      screening-detected indeterminate nodules in a high-risk population may be more
      limited than in a general population.

PMID- 15972413
TI  - Chest radiograph as a triage tool in the imaging-based diagnosis of pulmonary
      embolism.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether using a chest
      radiograph to triage patients being imaged for pulmonary embolism (PE) with
      pulmonary CT angiography (CTA) or ventilation-perfusion scintigraphy resulted in
      fewer indeterminate imaging results. CONCLUSION: Chest radiograph can be a
      valuable triage tool in deciding an appropriate technique for imaging PE, and can
      yield more definitive diagnoses.

PMID- 15972414
TI  - Helical CT for the evaluation of acute pulmonary embolism.
AB  - OBJECTIVE: In this article, we review the current role of CT pulmonary
      angiography and indirect CT venography for the evaluation of pulmonary
      thromboembolic disease. CONCLUSION: With advances in MDCT technology, evaluation
      of pulmonary thromboembolic disease can now be performed with combined CT
      pulmonary angiography and CT venography as a "one-stop-shopping" test. CT
      pulmonary angiography is cost-effective, is accurate, has high interobserver
      agreement, and has an added advantage of detecting other life-threatening
      diseases in the chest that mimic pulmonary embolism.

PMID- 15972415
TI  - An unusual case of systemic arterial supply to the lung with bronchial atresia.

PMID- 15972416
TI  - MRI of sarcoidosis patients with musculoskeletal symptoms.
AB  - OBJECTIVE: Our objective was to determine MRI findings in sarcoidosis patients
      with musculoskeletal symptoms. CONCLUSION: In sarcoidosis patients with
      musculoskeletal complaints, MRI reveals marrow and soft-tissue lesions that are
      occult or underestimated on radiographs. Axial and large-bone lesions may
      resemble osseous metastases on MRI. Most lesions detected are nonspecific in
      appearance, except nodular muscle lesions. MRI reveals features suggesting the
      diagnosis, but with standard protocols, no pathognomonic MRI features were
      determined.

PMID- 15972417
TI  - Intramuscular rotator cuff cysts: association with tendon tears on MRI and
      arthroscopy.
AB  - OBJECTIVE: This study was designed to explore the relationship between
      intramuscular cysts and rotator cuff tendon tears. CONCLUSION: Intramuscular
      cysts are strongly associated with rotator cuff tendon tears. Identification of
      such a cyst should prompt a search for a rotator cuff tear. Findings on MR
      arthrography and surgery suggest that a delaminating component of the rotator
      cuff tear may lead to the development of these cysts and may explain the
      occasional discrepancy between location of tears and location of cysts.

PMID- 15972418
TI  - MRI findings of femoral diaphyseal stress injuries in athletes.

PMID- 15972419
TI  - Subungual squamous cell carcinoma of the finger.

PMID- 15972420
TI  - Bias in the medical journals: a commentary.
AB  - Most readers are not aware of the fact that medical journals may have an unspoken
      bias in the papers that they select for publication. These biases can have far
      reaching consequences. The controversy over mammography screening for women ages
      40-49 is a case in point. Several medical journals knowingly have refused to
      provide women with accurate information. Consequently, women have been led to
      believe that the age of 50 has some real significance with regard to screening
      when the fact is that it has none.

PMID- 15972421
TI  - MRI-guided 9-gauge vacuum-assisted breast biopsy: initial clinical experience.
AB  - OBJECTIVE: The objective of this study was to evaluate our initial clinical
      experience with MRI-guided vacuum-assisted breast biopsy as an alternative to
      surgical excision. MATERIALS AND METHODS: A retrospective review revealed 112
      consecutive nonpalpable, mammographically occult MRI-detected breast lesions
      scheduled for MRI-guided vacuum-assisted biopsy. Biopsy was performed with a 9
      gauge vacuum-assisted biopsy probe (Suros Surgical Systems) followed by clip
      placement (Artemis Medical). Medical records and histologic findings were
      reviewed. RESULTS: Among 112 lesions, biopsy was cancelled because of
      nonvisualization of the lesion in 14 (12%). Of the remaining 98 lesions, tissue
      was successfully acquired in 95 (97%). The median number of specimens obtained
      was 12 (range, 6-20). The median time to perform MRI-guided biopsy was 33 min for
      one lesion and 56 min for two lesions. Histology in 95 lesions was benign and
      concordant in 52 (55%), cancer in 24 (25%), high-risk in 10 (11%), and discordant
      in nine (9%). MRI-guided biopsy histologies in 24 cancers were ductal carcinoma
      in situ in 13 (54%) and infiltrating carcinoma in 11 (46%). Seven additional
      cancers were found at surgery in four discordant lesions and in three high-risk
      lesions. The clip successfully deployed in 86 (95%) of 91 lesions. Six
      complications (three hematomas, two instances in which the biopsy probe pierced
      the skin on the far side of the breast, and one vasovagal reaction) resolved
      without sequelae. CONCLUSION: MRI-guided vacuum-assisted biopsy is a fast and
      safe alternative to surgical biopsy for MRI-detected breast lesions. Imaging
      histologic correlation is necessary to ensure lesion sampling.

PMID- 15972422
TI  - Performance and reproducibility of a computerized mass detection scheme for
      digitized mammography using rotated and resampled images: an assessment.
AB  - OBJECTIVE: Our objective was to compare the performance and reproducibility of a
      computer-aided detection (CAD) scheme that uses multiple rotated and resampled
      images with an in-house-developed CAD scheme (single-image-based) and a
      commercial CAD product in detecting masses depicted on digitized mammograms.
      MATERIALS AND METHODS: Ninety-two film mammograms (acquired from 23 patients)
      were selected. Forty-four mass regions associated with malignancy were visually
      identified. A commercial CAD system was used to scan and process each image four
      times, for a total of 368 digitized images depicting 176 mass regions. Images
      were processed using two CAD schemes developed in our laboratory. One uses the
      detection results generated from a single image, and the other averages five
      detection scores generated after processing the originally digitized image and
      four slightly rotated and resampled images. A region-based analysis was used to
      compare reproducibility and performance levels among the two in-house schemes and
      the commercial system. RESULTS: The commercial system detected a total of 98 mass
      regions (55.7% sensitivity) and 136 false-positive regions (an average of 0.37
      per image). Among the detected mass regions, 76 represented 19 regions that were
      detected on all four scans and 22 represented 10 regions that were not fully
      reproducible. Eighty-eight false-positive detections represented 22 reproducible
      detections on all four scans. Our single-image-based scheme identified 87 mass
      regions and 160 false-positive regions. Seventeen mass regions and 28 false
      positive regions were detected on all four scans. The multiple-image-based scheme
      identified 98 mass regions and 132 false-positive regions. Twenty-three mass
      regions were detected on all four scans. One hundred twelve of the 132 false
      positive regions represented 28 reproducible detections. CONCLUSION: Averaging
      detection scores from multiple rotated and resampled images generated from a
      single digitization of a film can reduce variations in detection scores. Our
      multiple-image-based scheme improved both performance and reproducibility over
      the single-image-based scheme. The multiple-image-based scheme yielded an overall
      performance comparable to that of the commercial system but with improved
      reproducibility.

PMID- 15972423
TI  - MRI features of mucosa-associated lymphoid tissue lymphoma in the breast.

PMID- 15972424
TI  - Delayed migration of Gel Mark Ultra clip within 15 days of 11-gauge vacuum
      assisted stereotactic breast biopsy.

PMID- 15972425
TI  - CT and MRI findings of sex cord-stromal tumor of the ovary.
AB  - OBJECTIVE: The purpose of this article was to research the clinical and imaging
      features of sex cord-stromal tumors of the ovary to help in specific diagnosis of
      ovarian tumors. Sex cord-stromal tumors of the ovary are rare ovarian neoplasms,
      which arise from stromal cells and primitive sex cords in the ovary. The common
      types are granulosa cell tumors, fibrothecomas, sclerosing stromal tumors, and
      Sertoli-Leydig cell tumors. They account for most of the hormonally active
      ovarian tumors. They have characteristic imaging features in each type of the
      tumor. CONCLUSION: Clinical and radiologic clues are helpful in differential
      diagnosis from the more common epithelial tumors; sex cord-stromal tumors
      primarily are treated surgically and have generally good prognosis.

PMID- 15972426
TI  - A case of struma uteri.

PMID- 15972427
TI  - Abdominal lymphadenopathy in beta-thalassemia: MRI features and correlation with
      liver iron overload and posttransfusion chronic hepatitis C.
AB  - OBJECTIVE: The objective of our study was to describe the MRI features of
      abdominal lymphadenopathy in patients with beta-thalassemia major and investigate
      the relation of abdominal lymphadenopathy with the severity of iron overload and
      posttransfusion chronic hepatitis C. MATERIALS AND METHODS: Abdominal MRI studies
      of 60 consecutive patients with beta-thalassemia major, performed for
      quantification of liver iron overload at a single institution, were
      retrospectively studied for the presence of lymph nodes and their distribution,
      size, and number. The signal intensity ratios of liver, spleen, and the largest
      lymph node to the right paraspinous muscle (L/M, S/M, and LN/M, respectively)
      were calculated on T1-weighted gradient-echo images. MRI findings for the lymph
      nodes were compared with the histologically assigned activity level of chronic
      hepatitis C that was available in 17 patients who had undergone liver biopsy
      within 1 month of the MRI examination. RESULTS: Hypointense abdominal lymph nodes
      larger than 7 mm were seen in 19 (32%) of 60 thalassemic patients in perihepatic
      and paraortic distributions. Lymphadenopathy was related to both the severity of
      hepatic siderosis, as expressed by the L/M values, and the presence of chronic
      hepatitis C, given that 18 (95%) of the 19 thalassemic patients with
      lymphadenopathy had chronic hepatitis C. Moreover, thalassemic patients with a
      moderate or severe level of hepatic inflammation presented with abdominal
      lymphadenopathy more frequently than those with mild hepatic inflammation.
      CONCLUSION: The development of hypointense abdominal lymphadenopathy in patients
      with beta-thalassemia major who have received multiple transfusions depends both
      on the severity of liver iron overload and on the presence and the activity level
      of coexistent chronic hepatitis C.

PMID- 15972428
TI  - Quantitative assessment of colorectal cancer perfusion using MDCT: inter- and
      intraobserver agreement.
AB  - OBJECTIVE: The objective of our study was to determine inter- and intraobserver
      agreement of MDCT colorectal cancer perfusion measurements. SUBJECTS AND METHODS:
      Thirty-one patients (17 men, 14 women; median age, 69 years) with proven
      colorectal cancer were examined prospectively using MDCT. A 65-sec dynamic study
      (cine mode, 4 x 5 mm collimation) was acquired through the tumor after i.v.
      contrast administration (100 mL of iopamidol 350, 5 mL/sec). Tumor blood volume,
      blood flow, mean transit time, and permeability measurements were determined by
      two independent observers using commercial software. Inter- and intraobserver
      agreement was assessed using the Bland-Altman test. RESULTS: The mean difference
      for interobserver agreement (95% limits of agreement) was -0.81 mL/100 g tissue (
      3.14 to 1.52); -9.94 mL/100 g tissue/min (-51.43 to 32.65); -1.09 sec (-7.05 to
      4.86); and -2.90 mL/100 g tissue/min (-11.48 to 5.68) for blood volume, blood
      flow, mean transit time, and permeability, respectively. The intraclass
      correlation coefficient was 0.83, 0.89, 0.89, and 0.80, respectively. The mean
      difference for intraobserver agreement (95% limits of agreement) was 0.12 mL/100
      g tissue (-1.90 to 2.14); 0.02 mL/100 g tissue/min (-13.13 to 13.17); -0.19 sec (
      3.19 to 2.81); and 0.00 mL/100 g tissue/min (-2.45 to 2.45) for observer 1 and
      0.26 mL/100 g tissue (-1.46 to 1.98); 4.47 mL/100 g tissue/min (-26.65 to 35.59);
      -0.21 sec (-2.48 to 2.06); 1.08 mL/100 g tissue/min (-4.92 to 7.08) for observer
      2. The intraclass correlation coefficient was 0.86, 0.98, 0.97, 0.98 for observer
      1 and 0.93, 0.96, 0.99, and 0.94, respectively, for observer 2. CONCLUSION: There
      is greater inter- than intraobserver agreement for CT vascular perfusion
      measurements of primary colorectal cancer, which must be addressed for reliable
      clinical application in therapeutic monitoring.

PMID- 15972429
TI  - Evaluation of a 16-MDCT scanner in an emergency department: initial clinical
      experience and workflow analysis.
AB  - OBJECTIVE: MDCT is especially suited for emergency purposes because it allows
      rapid high-resolution scans of large areas, fast high-quality reformatting in
      every orientation, and 3D illustration of the data set. In a prospective study,
      we evaluated the reliability and workflow of a dedicated emergency department 16
      MDCT scanner in the management of patients presenting to the emergency
      department. SUBJECTS AND METHODS: The use of a 16-MDCT scanner for 503 patients
      in the emergency department of a university clinic was evaluated. For reasons of
      workflow analysis, seven precise time intervals were recorded during the
      emergency examinations. A new setting for repositioning multiple-trauma patients
      after imaging of the head and neck from the head-first position to the feet-first
      position was introduced. RESULTS: Six (1.2%) of the 503 patients were excluded
      because of technical malfunction or patient noncompliance. Image quality in the
      remaining 497 cases, including CT angiography and CT of multiple-trauma patients,
      was outstanding. Positioning of the patients took from 3 to 13 min depending on
      the body region examined, representing 33-67% of the mean room time, which ranged
      from 8 to 21 min. In multiple-trauma patients, the initial positioning took a
      mean of 6 min and repositioning took 8 min, representing 19% and 26% of total
      room time, respectively. CONCLUSION: The use of a dedicated 16-MDCT scanner in
      the emergency department resulted in short examination times even for
      examinations of multiple body regions under emergency conditions. The introduced
      setting-repositioning of multiple-trauma patients-allowed high image quality to
      be maintained. The trade-off in multiple-trauma patients was prolonged room time
      because of patient repositioning.

PMID- 15972430
TI  - Detection of liver metastases from adenocarcinoma of the colon and pancreas:
      comparison of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET.
AB  - OBJECTIVE: The objective of our study was to assess the relative performance of
      mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET for the
      detection of liver metastases from adenocarcinoma of the colon and pancreas.
      MATERIALS AND METHODS: Imaging data of 34 patients (23 men, 11 women; age range,
      44-78 years) with adenocarcinoma of the colon (n = 27) or adenocarcinoma of the
      pancreas (n = 7) who had undergone mangafodipir trisodium-enhanced liver MRI and
      whole-body FDG PET were retrospectively reviewed for the presence and number of
      liver metastases. Histopathology (n = 25) or follow-up imaging (n = 9) served as
      the standard of reference. Breath-hold T1-weighted gradient-recalled echo,
      respiratory-triggered T2-weighted fast spin-echo, and mangafodipir trisodium
      enhanced axial fat-saturated high-spatial-resolution (256 x 512) T1-weighted
      gradient-recalled echo images were obtained on a 1.5-T scanner. FDG PET was
      performed after the injection of 15-20 mCi (555-740 MBq) of FDG. The sensitivity,
      positive predictive value, and accuracy were calculated for each technique. The
      performances of the two techniques were compared using the Fisher's exact test.
      RESULTS: Thirty patients had hepatic metastases and four had no hepatic
      metastases according to the standard of reference. The total number of metastases
      was 79, including 33 that measured less than 1 cm. Based on a per-patient
      analysis, MRI and FDG PET showed sensitivities of 96.6% and 93.3%, positive
      predictive values of 100% and 90.3%, and accuracies of 97.1% and 85.3%,
      respectively. According to a per-lesion analysis, MRI and FDG PET showed
      sensitivities of 81.4% and 67.0%, positive predictive values of 89.8% and 81.3%,
      and accuracies of 75.5% and 64.1%, respectively. MRI detected more hepatic
      metastases than FDG PET (p = 0.016). Of the 33 subcentimeter lesions confirmed on
      the standard of reference, all were identified on MRI, whereas only 12 were
      detected on FDG PET (p = 0.0001). CONCLUSION: In patients with colon and
      pancreatic adenocarcinoma, high-spatial-resolution mangafodipir trisodium
      enhanced liver MRI and whole-body FDG PET were comparable in the detection of
      patients with liver metastases. FDG PET provided additional information about
      extrahepatic disease and was useful in initial staging. However, significantly
      more and smaller liver metastases were detected on MRI than on FDG PET.

PMID- 15972431
TI  - Relationship between vascular and biliary anatomy in living liver donors.
AB  - OBJECTIVE: The objective of our study was to determine whether there is an
      association between portal venous or hepatic arterial branching patterns (or
      both) and biliary anatomic variants. MATERIALS AND METHODS: Two radiologists
      independently reviewed preoperative hepatic CT scans and intraoperative
      cholangiograms from 39 consecutive living liver donors. The portal venous and
      hepatic arterial anatomy was classified on the basis of the preoperative CT scans
      and the biliary anatomy was classified on the basis the intraoperative
      cholangiograms into one of two groups: conventional or anomalous. Variables were
      tested for association using Fisher's exact test. RESULTS: Anomalous vascular
      branching variants were common, being present in 23 (59%) of 39 patients. Hepatic
      arterial anomalies were present in 18 (46%); portal venous anomalies, in seven
      (18%); and both, in two (5%). Biliary anomalies were present in 15 (38%) of the
      39 patients. Of the 23 patients with anomalous vascular anatomy, seven (30%) had
      biliary anomalies. Of the 16 patients with conventional vascular anatomy, eight
      (50%) had biliary anomalies. There was no significant association between hepatic
      arterial anomalies, portal venous anomalies, or the combination of arterial and
      portal venous anomalies and anomalous biliary drainage. CONCLUSION: Portal venous
      and hepatic arterial branching patterns do not correlate well with biliary
      anatomic variants. In patients with normal hepatic vascular anatomy, biliary
      anomalies are common.

PMID- 15972432
TI  - Clinical potentials for dynamic contrast-enhanced hepatic volumetric cine imaging
      with the prototype 256-MDCT scanner.
AB  - OBJECTIVE: To achieve dynamic contrast-enhanced hepatic volumetric cine imaging,
      we developed a prototype 256-MDCT scanner. This study examined the feasibility of
      the technique for human hepatic imaging in three hepatocellular carcinoma
      patients. CONCLUSION: Volumetric cine imaging successfully visualized dynamic
      contrast enhancement of the hepatocellular carcinoma. It is helpful to evaluate
      the phase of contrast enhancement or for functional studies of the head, renal
      artery, coronary artery, and liver.

PMID- 15972433
TI  - Urethral bulking agents: imaging review.
AB  - OBJECTIVE: At imaging, injectable bulking materials used for urinary incontinence
      have the potential to mimic urethral and periurethral pathology. This article
      elucidates the appearance of the most commonly used agents in multiple techniques
      and helps the practicing radiologist avoid potential diagnostic pitfalls.
      CONCLUSION: Carbon-coated microbeads (Durasphere) and cross-linked bovine
      collagen (Contigen) have fairly characteristic imaging appearances and can in
      most cases be differentiated from true pathology.

PMID- 15972434
TI  - Papillary glioneuronal tumor.

PMID- 15972435
TI  - Renal medullary carcinoma: CT and MRI features.
AB  - OBJECTIVE: We review the cross-sectional imaging findings of six cases of
      pathologically proven renal medullary carcinoma in patients with sickle cell
      trait. MRI findings were available in three of the patients. To our knowledge,
      only one previous report has addressed MRI features of this rare disease.
      CONCLUSION: In young patients with sickle cell trait, an infiltrative renal mass
      with associated retroperitoneal adenopathy and caliectasis are characteristic
      findings of renal medullary carcinoma on CT and MRI.

PMID- 15972436
TI  - Using PowerPoint to create high-resolution images for journal publications.
AB  - OBJECTIVE: In this article, I describe the essential steps for using PowerPoint
      to create high-resolution images for radiology journal publications. CONCLUSION:
      PowerPoint 2003 can be used as an alternative to create high-resolution images
      for journal publications without the need for other image-processing software.

PMID- 15972437
TI  - CT-based acetabular fracture classification.

PMID- 15972438
TI  - Cement emboli in vertebroplasty and kyphoplasty.

PMID- 15972439
TI  - Omental infarction: a self-limiting disease.

PMID- 15972440
TI  - Author's correction. Detection of combined hepatocellular and cholangiocarcinomas
      on enhanced CT: comparison with histologic findings.

PMID- 15972441
TI  - Pseudoaneurysm of the calf after electromyography: sonographic and CT
      angiographic diagnosis.

PMID- 15972442
TI  - Giant thymolipoma.

PMID- 15972443
TI  - Inguinal herniation of the ureter.

PMID- 15972444
TI  - Endometriosis in the canal of Nuck: atypical manifestations in an unusual
      location.

PMID- 15972445
TI  - Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic
      leukemia cell death.
AB  - Flavopiridol is active against chronic lymphocytic leukemia (CLL) cells in vitro
      and in the treatment of advanced stage disease, but the mechanisms of these
      actions remain unclear. Originally developed as a general cyclin-dependent kinase
      inhibitor, flavopiridol is a potent transcriptional suppressor through the
      inhibition of positive transcription elongation factor b (P-TEFb; CDK9/cyclin T).
      P-TEFb phosphorylates the C-terminal domain (CTD) of RNA polymerase II to promote
      transcriptional elongation. Because most CLL cells are not actively cycling, and
      their viability is dependent upon the continuous expression of antiapoptotic
      proteins, we hypothesized that flavopiridol induces apoptosis in CLL cells
      through the transcriptional down-regulation of such proteins. This study
      demonstrated that flavopiridol inhibited the phosphorylation of the CTD of RNA
      polymerase II in primary CLL cells and reduced RNA synthesis. This was associated
      with a decline of the transcripts and the levels of short-lived antiapoptotic
      proteins such as myeloid cell leukemia 1 (Mcl-1), and resulted in the induction
      of apoptosis. The B-cell lymphoma 2 (Bcl-2) protein level remained stable,
      although its mRNA was consistently reduced, suggesting that the outcome of
      transcriptional inhibition by flavopiridol is governed by the intrinsic stability
      of the individual transcripts and proteins. The dependence of CLL-cell survival
      on short-lived oncoproteins may provide the biochemical basis for the therapeutic
      index in response to flavopiridol.

PMID- 15972446
TI  - Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell
      leukemia with the D816V KIT mutation.
AB  - The majority of patients with systemic mast cell disease express the imatinib
      resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Limited
      treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell
      leukemia (MCL). We evaluated whether PKC412, a small-molecule inhibitor of KIT
      with a different chemical structure from imatinib, may have therapeutic use in
      advanced SM with the D816V KIT mutation. We treated a patient with MCL (with an
      associated myelodysplastic syndrome (MDS)/myeloproliferative disorder [MPD])
      based on in vitro studies demonstrating that PKC412 could inhibit D816V KIT
      transformed Ba/F3 cell growth with a 50% inhibitory concentration (IC50) of 30 nM
      to 40 nM. The patient exhibited a partial response with significant resolution of
      liver function abnormalities. In addition, PKC412 treatment resulted in a
      significant decline in the percentage of peripheral blood mast cells and serum
      histamine level and was associated with a decrease in KIT phosphorylation and
      D816V KIT mutation frequency. The patient died after 3 months of therapy due to
      progression of her MDS/MPD to acute myeloid leukemia (AML). This case indicates
      that KIT tyrosine kinase inhibition is a feasible approach in SM, but single
      agent clinical efficacy may be limited by clonal evolution in the advanced
      leukemic phase of this disease.

PMID- 15972447
TI  - Aggregometry detects platelet hyperreactivity in healthy individuals.
AB  - Aggregometry is widely used to assess platelet function, but its use in
      identifying platelet hyperreactivity is poorly defined. We studied platelet
      aggregation in 359 healthy individuals using the agonists adenosine diphosphate
      (ADP), epinephrine, collagen, collagen-related peptide, and ristocetin. We also
      assessed the reproducibility of these assays in 27 subjects by studying them
      repeatedly on at least 4 separate occasions. Healthy subjects exhibited
      considerable interindividual variability in aggregation response to agonists,
      especially at concentrations lower than those typically used in clinical
      laboratories. For each agonist tested at these submaximal concentrations, a small
      proportion of individuals demonstrated an unusually robust aggregation response.
      Subjects who exhibited such in vitro hyperreactivity to one agonist tended to
      demonstrate a similar response to others, suggesting that hyperreactivity is a
      global characteristic of platelets. Epinephrine and collagen-related peptide were
      especially reliable and efficient in detecting hyperreactivity. For epinephrine,
      excellent reproducibility persisted for up to 3 years, and hyperreactivity was
      associated with female sex and higher fibrinogen levels (P < .02). We recommend
      these assays as appropriate candidates for future studies requiring accurate
      assessment of increased platelet reactivity. These include clinical studies to
      improve risk assessment for arterial thrombosis, as well as genetic studies to
      establish determinants of the hyperreactive platelet phenotype.

PMID- 15972448
TI  - Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic
      graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic
      hematopoietic stem cell transplantation but the immune mechanisms leading to the
      diverse clinical manifestations of cGVHD remain unknown. In this study, we
      examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD
      and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies
      demonstrated decreased frequency of CD4+CD25+ T cells in patients with cGVHD
      compared with patients without cGVHD (P < .001) and healthy individuals (P <
      .001). Gene expression of Treg transcription factor FOXP3 was reduced in cGVHD
      patients compared with patients without cGVHD (P = .009) or healthy donors (P =
      .01). T-cell receptor excision circle (TREC) assays for the evaluation of thymus
      activity revealed fewer TRECs in both transplant groups compared with healthy
      donors (P < .001 and P = .02, respectively) although no difference was observed
      between patients with or without cGVHD (P = .13). When tested in functional
      assays, Tregs from both patient cohorts and healthy individuals mediated
      equivalent levels of suppression. Collectively, these studies indicate that
      patients with active cGVHD have reduced frequencies of Tregs but the function of
      these cells remains normal. These findings support the development of new
      strategies to increase the number of Tregs following allogeneic hematopoietic
      stem cell transplantation to prevent or correct cGVHD.

PMID- 15972449
TI  - ZAP-70 is a novel conditional heat shock protein 90 (Hsp90) client: inhibition of
      Hsp90 leads to ZAP-70 degradation, apoptosis, and impaired signaling in chronic
      lymphocytic leukemia.
AB  - The zeta-associated protein of 70 kDa (ZAP-70) is expressed in patients with
      aggressive chronic lymphocytic leukemia (CLL). We found that ZAP-70+ CLL cells
      expressed activated heat-shock protein 90 (Hsp90) with high binding affinity for
      Hsp90 inhibitors, such as 17-allyl-amino-demethoxy-geldanamycin (17-AAG), whereas
      normal lymphocytes or ZAP-70- CLL cells expressed nonactivated Hsp90. Activated
      Hsp90 bound and stabilized ZAP-70, which behaved like an Hsp90 client protein
      only in CLL cells. Treatment with Hsp90 inhibitors such as 17-AAG and 17
      dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) induced ZAP-70
      degradation and apoptosis in CLL cells but not in T cells, and also impaired B
      cell receptor signaling in leukemia cells. Transduction of ZAP-70- CLL cells with
      an adenovirus encoding ZAP-70 activated Hsp90 and specifically rendered the
      leukemia cells sensitive to 17-AAG. These data indicate that Hsp90 is necessary
      for ZAP-70 expression and activity; that ZAP-70 is unique among Hsp90 clients, in
      that its chaperone-dependency is conditional on the cell type in which it is
      expressed; and also that ZAP-70 is required for cell survival and signaling in
      CLL. Additionally, ZAP-70 expression in CLL cells confers markedly heightened
      sensitivity to 17-AAG or 17-DMAG, suggesting that these or other Hsp90 inhibitors
      could be valuable therapeutically in patients with aggressive CLL.

PMID- 15972450
TI  - c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma
      associated antiapoptotic mutations.
AB  - Ectopic expression of c-Myc (Myc) in most primary cell types results in
      programmed cell death, and malignant transformation cannot occur without
      additional mutations that block apoptosis. The development of Myc-induced
      lymphoid tumors has been well studied and supports this model. Myc can be
      upregulated in acute myeloid leukemia (AML), but its exact role in myeloid
      leukemogenesis is unclear. To study its role in AML, we used a murine stem cell
      virus (MSCV) retroviral gene transfer/transplantation system to broadly express
      Myc in the bone marrow of mice either alone or in combination with antiapoptotic
      mutations. Myc expression in the context either of Arf/Ink4a loss or Bcl-2
      coexpression induced a mixture of acute myeloid and acute lymphoid leukemias
      (AML+ALL). In the absence of antiapoptotic mutations however, all mice
      transplanted with MSCV-Myc (100%, n = 110) developed AML exclusively. MSCV-Myc
      induced AML was polyclonal, readily transplantable, possessed an intact Arf-p53
      pathway, and did not display cytogenetic abnormalities by spectral karyotyping
      (SKY) analysis. Lastly, we found that Myc preferentially stimulated the growth of
      myeloid progenitor cells in methylcellulose. These data provide the first direct
      evidence that Myc is a critical downstream effector of myeloid leukemogenesis and
      suggest that myeloid progenitors are intrinsically resistant to Myc-induced
      apoptosis.

PMID- 15972451
TI  - In vivo aspirin supplementation inhibits nitric oxide consumption by human
      platelets.
AB  - Antiplatelet therapies improve endothelial function in atherosclerosis,
      suggesting that platelets regulate vascular nitric oxide (NO) bioactivity in
      vivo. Herein, washed platelets consumed NO on activation in an aspirin-sensitive
      manner, and aspirin enhanced platelet NO responses in vitro. To examine whether
      in vivo aspirin can inhibit platelet NO consumption, a double-blind placebo
      controlled study was conducted. After a 2-week nonsteroidal anti-inflammatory
      drug (NSAID)-free period, healthy men were randomly assigned and administered
      aspirin (75 mg/d orally) or identical placebo for 14 days, then crossed over to
      the opposite arm. Following in vivo aspirin, NO consumption by platelets was
      inhibited 91%. Rate of onset and recovery following aspirin withdrawal was
      consistent with cyclooxygenase 1 (COX-1) inhibition. In a small substudy, NO
      consumption by platelets from postmenopausal women was faster in
      hypercholesterolemics and less sensitive to aspirin (ie, 39% versus 76%
      inhibition for hypercholesterolemics or normocholesterolemics, respectively).
      However, 150 mg aspirin/day increased inhibition of NO consumption by platelets
      of hypercholesterolemics to 80%. Comparisons of platelet COX-1 or -2 expression
      and urinary 11-dehydro-thromboxane B2 excretion suggested that aspirin was less
      able to block platelet activation in vivo in hypercholesterolemia. In conclusion,
      aspirin inhibits NO consumption by platelets from healthy subjects, but its
      beneficial effects on NO bioactivity may be compromised in some
      hypercholesterolemic patients.

PMID- 15972452
TI  - CXCL13 is an arrest chemokine for B cells in high endothelial venules.
AB  - Chemokine receptor signaling is critical for lymphocyte trafficking across high
      endothelial venules (HEVs), but the exact mode of action of individual chemokines
      expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a
      substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs),
      serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs
      (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13-/
      mice and that B-cell adhesion is substantially restored in CXCL13-/- HEVs when
      CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP
      HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine
      triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a
      deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in
      shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In
      addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion
      molecule 1 (MAdCAM-1) by activating alpha4 integrin. These data identify CXCL13
      as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an
      important role in B-cell entry into not only PPs but also MLNs.

PMID- 15972453
TI  - Difference in clinical features between Japanese and German patients with
      refractory anemia in myelodysplastic syndromes.
AB  - Several reports indicate that there might be differences in clinical features
      between Asian and Western myelodysplastic syndrome (MDS) cases. We analyzed
      refractory anemia (RA) in French-American-British (FAB) classification cases
      diagnosed in Japan and Germany to perform a more exact comparison between Asian
      and Western MDS types. In the first step, we analyzed agreement of morphologic
      diagnosis between Japanese and German hematologists. Blood and bone marrow slides
      of 129 patients diagnosed with FAB-RA, FAB-RA with ringed sideroblasts (RARS), or
      aplastic anemia were selected randomly and evaluated separately by each group.
      The agreements of diagnoses according to FAB and World Health Organization (WHO)
      classifications were 98.4% and 83.8%, respectively. Second, we compared clinical
      features between 131 Japanese and 597 German patients with FAB-RA. Japanese
      patients were significantly younger than German patients. Japanese patients had
      more severe cytopenias. However, prognosis of Japanese patients was significantly
      more favorable than that of German patients. Japanese patients had a
      significantly lower cumulative risk of acute leukemia evolution than did German
      patients. Frequency of WHO-RA in Japanese patients with FAB-RA was significantly
      higher than that in German patients. In conclusion, our results indicate that the
      clinical features of Japanese patients with FAB-RA differ from those of German
      patients.

PMID- 15972454
TI  - Therapeutic expression of the platelet-specific integrin, alphaIIbbeta3, in a
      murine model for Glanzmann thrombasthenia.
AB  - Integrins mediate the adhesion of cells to each other and to the extracellular
      matrix during development, immunity, metastasis, thrombosis, and wound healing.
      Molecular defects in either the alpha- or beta-subunit can disrupt integrin
      synthesis, assembly, and/or binding to adhesive ligands. This is exemplified by
      the bleeding disorder, Glanzmann thrombasthenia (GT), where abnormalities of the
      platelet-specific integrin, alphaIIbbeta3, prevent platelet aggregation following
      vascular injury. We previously used a retrovirus vector containing a cDNA
      cassette encoding human integrin beta3 to restore integrin alphaIIbbeta3 on the
      surface of megakaryocytes derived from peripheral blood stem cells of GT
      patients. In the present study, bone marrow from beta3-deficient (beta3-/-) mice
      was transduced with the ITGbeta3-cassette to investigate whether the platelet
      progeny could establish hemostasis in vivo. A lentivirus transfer vector equipped
      with the human ITGA2B gene promoter confined transgene expression to the platelet
      lineage. Human beta3 formed a stable complex with murine alphaIIb, effectively
      restoring platelet function. Mice expressing significant levels of alphaIIbbeta3
      on circulating platelets exhibited improved bleeding times. Intravenous
      immunoglobulin effectively diminished platelet clearance in animals that
      developed an antibody response to alphaIIbbeta3. These results indicate the
      feasibility of targeting platelets with genetic therapies for better management
      of patients with inherited bleeding disorders.

PMID- 15972455
TI  - Premating, not postmating, barriers drive genetic dynamics in experimental hybrid
      populations of the endangered Sonoran topminnow.
AB  - The timing and pattern of reproductive barrier formation in allopatric
      populations has received much less attention than the accumulation of
      reproductive barriers in sympatry. The theory of allopatric speciation suggests
      that reproductive barriers evolve simply as by-products of overall genetic
      divergence. However, observations of enhanced premating barriers in allopatric
      populations suggest that sexual selection driven by intraspecific competition for
      mates may enhance species-specific signals and accelerate the speciation process.
      In a previous series of laboratory trials, we examined the strength of premating
      and postmating barriers in an allopatric species pair of the endangered Sonoran
      topminnow, Poeciliopsis occidentalis and P. sonoriensis. Behavioral observations
      provided evidence of asymmetrical assortative mating, while reduced brood sizes
      and male-biased F(1) sex ratios suggest postmating incompatibilities. Here we
      examine the combined effects of premating and postmating barriers on the genetic
      makeup of mixed populations, using cytonuclear genotype frequencies of first- and
      second-generation offspring. Observed genotype frequencies strongly reflect the
      directional assortative mating observed in behavioral trials, illustrating how
      isolating barriers that act earlier in the reproductive cycle will have a greater
      effect on total reproductive isolation and may be more important to speciation
      than subsequent postmating reproductive barriers.

PMID- 15972456
TI  - Brc1-mediated DNA repair and damage tolerance.
AB  - The structural maintenance of chromosome (SMC) proteins are key elements in
      controlling chromosome dynamics. In eukaryotic cells, three essential SMC
      complexes have been defined: cohesin, condensin, and the Smc5/6 complex. The
      latter is essential for DNA damage responses; in its absence both repair and
      checkpoint responses fail. In fission yeast, the UV-C and ionizing radiation (IR)
      sensitivity of a specific hypomorphic allele encoding the Smc6 subunit, rad18-74
      (renamed smc6-74), is suppressed by mild overexpression of a six-BRCT-domain
      protein, Brc1. Deletion of brc1 does not result in a hypersensitivity to UV-C or
      IR, and thus the function of Brc1 relative to the Smc5/6 complex has remained
      unclear. Here we show that brc1Delta cells are hypersensitive to a range of
      radiomimetic drugs that share the feature of creating lesions that are an
      impediment to the completion of DNA replication. Through a genetic analysis of
      brc1Delta epistasis and by defining genes required for Brc1 to suppress smc6-74,
      we find that Brc1 functions to promote recombination through a novel
      postreplication repair pathway and the structure-specific nucleases Slx1 and
      Mus81. Activation of this pathway through overproduction of Brc1 bypasses a
      repair defect in smc6-74, reestablishing resolution of lesions by recombination.

PMID- 15972457
TI  - Quantitative trait loci affecting the difference in pigmentation between
      Drosophila yakuba and D. santomea.
AB  - Using quantitative trait locus (QTL) mapping, we studied the genetic basis of the
      difference in pigmentation between two sister species of Drosophila: Drosophila
      yakuba, which, like other members of the D. melanogaster subgroup, shows heavy
      black pigmentation on the abdomen of males and females, and D. santomea, an
      endemic to the African island of Sao Tome, which has virtually no pigmentation.
      Here we mapped four QTL with large effects on this interspecific difference in
      pigmentation: two on the X chromosome and one each on the second and third
      chromosomes. The same four QTL were detected in male hybrids in the backcrosses
      to both D. santomea and D. yakuba and in the female D. yakuba backcross hybrids.
      All four QTL exhibited strong epistatic interactions in male backcross hybrids,
      but only one pair of QTL interacted in females from the backcross to D. yabuka.
      All QTL from each species affected pigmentation in the same direction, consistent
      with adaptive evolution driven by directional natural selection. The regions
      delimited by the QTL included many positional candidate loci in the pigmentation
      pathway, including genes affecting catecholamine biosynthesis, melanization of
      the cuticle, and many additional pleiotropic effects.

PMID- 15972458
TI  - Estimating the time to the whole-genome duplication and the duration of concerted
      evolution via gene conversion in yeast.
AB  - A maximum-likelihood (ML) method is developed to estimate the duration of
      concerted evolution and the time to the whole-genome duplication (WGD) event in
      baker's yeast (Saccharomyces cerevisiae). The models with concerted evolution fit
      the data significantly better than the molecular clock model, indicating a
      crucial role of concerted evolution via gene conversion after gene duplication in
      yeast. Our ML estimate of the time to the WGD is nearly identical to the time to
      the speciation event between S. cerevisiae and Kluyveromyces waltii, suggesting
      that the WGD occurred in very early stages after speciation or the WGD might have
      been involved in the speciation event.

PMID- 15972459
TI  - Phenotypic selection for dormancy introduced a set of adaptive haplotypes from
      weedy into cultivated rice.
AB  - Association of seed dormancy with shattering, awn, and black hull and red
      pericarp colors enhances survival of wild and weedy species, but challenges the
      use of dormancy genes in breeding varieties resistant to preharvest sprouting. A
      phenotypic selection and recurrent backcrossing technique was used to introduce
      dormancy genes from a wild-like weedy rice to a breeding line to determine their
      effects and linkage with the other traits. Five generations of phenotypic
      selection alone for low germination extremes simultaneously retained dormancy
      alleles at five independent QTL, including qSD12 (R(2) > 50%), as determined by
      genome-wide scanning for their main and/or epistatic effects in two BC(4)F(2)
      populations. Four dormancy loci with moderate to small effects colocated with
      QTL/genes for one to three of the associated traits. Multilocus response to the
      selection suggests that these dormancy genes are cumulative in effect, as well as
      networked by epistases, and that the network may have played a "sheltering" role
      in maintaining intact adaptive haplotypes during the evolution of weeds. Tight
      linkage may prevent the dormancy genes from being used in breeding programs. The
      major effect of qSD12 makes it an ideal target for map-based cloning and the best
      candidate for imparting resistance to preharvest sprouting.

PMID- 15972460
TI  - The element(s) at the nontranscribed Xist locus of the active X chromosome
      controls chromosomal replication timing in the mouse.
AB  - In female mammalian cells, the inactive X chromosome is replicated late in S
      phase while the active X chromosome is replicated earlier. The replication times
      of the X chromosomes reflect a general trend in which late replication is
      associated with gene repression and earlier replication with transcriptional
      competence. The X-linked Xist gene is expressed exclusively from the inactive X
      chromosome where it is involved in the initiation and maintenance of X
      inactivation. In contrast, no biological activity has been assigned to the Xist
      locus of the active X chromosome where the Xist gene is transcriptionally
      silenced. Here, we provide evidence that the element(s) at the nontranscribed
      Xist locus of the active X chromosome controls chromosomal replication timing in
      cis.

PMID- 15972461
TI  - A role for the Saccharomyces cerevisiae regulation of Ace2 and polarized
      morphogenesis signaling network in cell integrity.
AB  - Saccharomyces cerevisiae RAM is a conserved signaling network that regulates
      maintenance of polarized growth and daughter-cell-specific transcription, the
      latter of which is critical for septum degradation. Consequently, cells defective
      in RAM function (designated ramDelta) are round in morphology, form feeble mating
      projections, and fail to separate following cytokinesis. It was recently
      demonstrated that RAM genes are essential in strains containing functional SSD1
      (SSD1-v), which encodes a protein of unknown function that binds the RAM Cbk1p
      kinase. Here we investigated the essential function of RAM in SSD1-v strains and
      identified two functional groups of dosage suppressors for ramDelta lethality. We
      establish that all ramDelta mutants exhibit cell integrity defects and cell
      lysis. All dosage suppressors rescue the lysis but not the cell polarity or cell
      separation defects of ramDelta cells. One class of dosage suppressors is composed
      of genes encoding cell wall proteins, indicating that alterations in cell wall
      structure can rescue the cell lysis in ramDelta cells. Another class of ramDelta
      dosage suppressors is composed of ZRG8 and SRL1, which encode two unrelated
      proteins of unknown function. We establish that ZRG8 and SRL1 share similar
      genetic interactions and phenotypes. Significantly, Zrg8p coprecipitates with
      Ssd1p, localizes similarly to RAM proteins, and is dependent on RAM for
      localization. Collectively, these data indicate that RAM and Ssd1p function
      cooperatively to control cell integrity and suggest that Zrg8p and Srl1p function
      as nonessential inhibitors of Ssd1p.

PMID- 15972462
TI  - A genetic linkage map for the tiger pufferfish, Takifugu rubripes.
AB  - The compact genome of the tiger pufferfish, Takifugu rubripes (fugu), has been
      sequenced to the "draft" level and annotated to identify all the genes. However,
      the assembly of the draft genome sequence is highly fragmented due to the lack of
      a genetic or a physical map. To determine the long-range linkage relationship of
      the sequences, we have constructed the first genetic linkage map for fugu. The
      maps for the male and female spanning 697.1 and 1213.5 cM, respectively, were
      arranged into 22 linkage groups by markers heterozygous in both parents. The
      resulting map consists of 200 microsatellite loci physically linked to genome
      sequences spanning approximately 39 Mb in total. Comparisons of the genome maps
      of fugu, other teleosts, and mammals suggest that syntenic relationship is more
      conserved in the teleost lineage than in the mammalian lineage. Map comparisons
      also show a pufferfish lineage-specific rearrangement of the genome resulting in
      colocalization of two Hox gene clusters in one linkage group. This map provides a
      foundation for development of a complete physical map, a basis for comparison of
      long-range linkage of genes with other vertebrates, and a resource for mapping
      loci responsible for phenotypic differences among Takifugu species.

PMID- 15972463
TI  - Minos as a genetic and genomic tool in Drosophila melanogaster.
AB  - Much of the information about the function of D. melanogaster genes has come from
      P-element mutagenesis. The major drawback of the P element, however, is its
      strong bias for insertion into some genes (hotspots) and against insertion into
      others (coldspots). Within genes, 5'-UTRs are preferential targets. For the
      successful completion of the Drosophila Genome Disruption Project, the use of
      transposon vectors other than P will be necessary. We examined here the
      suitability of the Minos element from Drosophila hydei as a tool for Drosophila
      genomics. Previous work has shown that Minos, a member of the Tc1/mariner family
      of transposable elements, is active in diverse organisms and cultured cells; it
      produces stable integrants in the germ line of several insect species, in the
      mouse, and in human cells. We generated and analyzed 96 Minos integrations into
      the Drosophila genome and devised an efficient "jump-starting" scheme for
      production of single insertions. The ratio of insertions into genes vs.
      intergenic DNA is consistent with a random distribution. Within genes, there is a
      statistically significant preference for insertion into introns rather than into
      exons. About 30% of all insertions were in introns and approximately 55% of
      insertions were into or next to genes that have so far not been hit by the P
      element. The insertion sites exhibit, in contrast to other transposons, little
      sequence requirement beyond the TA dinucleotide insertion target. We further
      demonstrate that induced remobilization of Minos insertions can delete nearby
      sequences. Our results suggest that Minos is a useful tool complementing the P
      element for insertional mutagenesis and genomic analysis in Drosophila.

PMID- 15972464
TI  - Maximum-likelihood methods for detecting recent positive selection and localizing
      the selected site in the genome.
AB  - Two maximum-likelihood methods are proposed for detecting recent, strongly
      positive selection and for localizing the target of selection along a recombining
      chromosome. The methods utilize the compact mutation frequency spectrum at
      multiple neutral loci that are partially linked to the selected site. Using
      simulated data, we show that the power of the tests lies between 80 and 98% in
      most cases, and the false positive rate could be as low as approximately 10% when
      the number of sampled marker loci is sufficiently large (> or = 20). The
      confidence interval around the estimated position of selection is reasonably
      narrow. The methods are applied to X chromosome data of Drosophila melanogaster
      from a European and an African population. Evidence of selection was found for
      both populations (including a selective sweep that was shared between both
      populations).

PMID- 15972465
TI  - Widespread correlations between dominance and homozygous effects of mutations:
      implications for theories of dominance.
AB  - The dominance of deleterious mutations has important consequences for phenomena
      such as inbreeding depression, the evolution of diploidy, and levels of natural
      genetic variation. Kacser and Burns' metabolic theory provides a paradigmatic
      explanation for why most large-effect mutations are recessive. According to the
      metabolic theory, the recessivity of large-effect mutations is a consequence of a
      diminishing-returns relationship between flux through a metabolic pathway and
      enzymatic activity at any step in the pathway, which in turn is an inevitable
      consequence of long metabolic pathways. A major line of support for this theory
      was the demonstration of a negative correlation between homozygous effects and
      dominance of mutations in Drosophila, consistent with a central prediction of the
      metabolic theory. Using data on gene deletions in yeast, we show that a negative
      correlation between homozygous effects and dominance of mutations exists for all
      major categories of genes analyzed, not just those encoding enzymes. The
      relationship between dominance and homozygous effects is similar for duplicated
      and single-copy genes and for genes whose products are members of protein
      complexes and those that are not. A complete explanation of dominance therefore
      requires either a generalization of Kacser and Burns' theory to nonenzyme genes
      or a new theory.

PMID- 15972466
TI  - A genetic screen for maternal-effect suppressors of decapentaplegic identifies
      the eukaryotic translation initiation factor 4A in Drosophila.
AB  - The Dpp signaling pathway is essential for many developmental processes in
      Drosophila and its activity is tightly regulated. To identify additional
      regulators of Dpp signaling, we conducted a genetic screen for maternal-effect
      suppressors of dpp haplo-insufficiency. We screened approximately 7000 EMS
      mutagenized genomes and isolated and mapped seven independent dominant
      suppressors of dpp, Su(dpp), which were recovered as second-site mutations that
      resulted in viable flies in trans-heterozygous with dpp(H46), a dpp null allele.
      Most of the Su(dpp) mutants exhibited increased cell numbers of the amnioserosa,
      a cell type specified by the Dpp pathway, suggesting that these mutations may
      augment Dpp signaling activity. Here we report the unexpected identification of
      one of the Su(dpp) mutations as an allele of the eukaryotic translation
      initiation factor 4A (eIF4A). We show that Su(dpp)(YE9) maps to eIF4A and that
      this allele is associated with a substitution, arginine 321 to histidine, at a
      well-conserved amino acid and behaves genetically as a dominant-negative
      mutation. This result provides an intriguing link between a component of the
      translation machinery and Dpp signaling.

PMID- 15972467
TI  - Host as the variable: model hosts approach the immunological asymptote.

PMID- 15972468
TI  - Worms and flies as genetically tractable animal models to study host-pathogen
      interactions.

PMID- 15972469
TI  - Galleria mellonella as a model system to study Cryptococcus neoformans
      pathogenesis.
AB  - Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts
      suggests that C. neoformans is a nonspecific pathogen. We used the killing of
      Galleria mellonella (the greater wax moth) caterpillar by C. neoformans to
      develop an invertebrate host model system that can be used to study cryptococcal
      virulence, host immune responses to infection, and the effects of antifungal
      compounds. All varieties of C. neoformans killed G. mellonella. After injection
      into the insect hemocoel, C. neoformans proliferated and, despite successful
      phagocytosis by host hemocytes, killed caterpillars both at 37 degrees C and 30
      degrees C. The rate and extent of killing depended on the cryptococcal strain and
      the number of fungal cells injected. The sequenced C. neoformans clinical strain
      H99 was the most virulent of the strains tested and killed caterpillars with
      inocula as low as 20 CFU/caterpillar. Several C. neoformans genes previously
      shown to be involved in mammalian virulence (CAP59, GPA1, RAS1, and PKA1) also
      played a role in G. mellonella killing. Combination antifungal therapy
      (amphotericin B plus flucytosine) administered before or after inoculation was
      more effective than monotherapy in prolonging survival and in decreasing the
      tissue burden of cryptococci in the hemocoel. The G. mellonella-C. neoformans
      pathogenicity model may be a substitute for mammalian models of infection with C.
      neoformans and may facilitate the in vivo study of fungal virulence and efficacy
      of antifungal therapies.

PMID- 15972470
TI  - Arrangement of the translocator of the autotransporter adhesin involved in
      diffuse adherence on the bacterial surface.
AB  - Autotransporters of gram-negative bacteria are single-peptide secretion systems
      that consist of a functional N-terminal alpha-domain ("passenger") fused to a C
      terminal beta-domain ("translocator"). How passenger proteins are translocated
      through the outer membrane has not been resolved, and at present essentially
      three different models are discussed. In the widely accepted "hairpin model" the
      passenger proteins are translocated through a channel formed by the beta-barrel
      of the translocator that is integrated in the outer membrane. This model has been
      challenged by a recent proposal for a general autotransporter model suggesting
      that there is a hexameric translocation pore that is generated by the
      oligomerization of six beta-domains. A third model suggests that conserved Omp85
      participates in autotransporter integration and passenger protein translocation.
      To examine these models, in this study we investigated the presence of putative
      oligomeric structures of the translocator of the autotransporter adhesin involved
      in diffuse adherence (AIDA) in vivo by cross-linking techniques. Furthermore, the
      capacity of isolated AIDA fusion proteins to form oligomers was studied in vitro
      by several complementary analytical techniques, such as analytical gel
      filtration, electron microscopy, immunogold labeling, and cross-linking of
      recombinant autotransporter proteins in which different passenger proteins were
      fused to the AIDA translocator. Our results show that the AIDA translocator is
      mostly present as a monomer. Only a fraction of the AIDA autotransporter was
      found to form dimers on the bacterial surface and in solution. Higher-order
      structures, such as hexamers, were not detected either in vivo or in vitro and
      can therefore be excluded as functional moieties for the AIDA autotransporter.

PMID- 15972471
TI  - Tyrosine phosphorylation of the chlamydial effector protein Tarp is species
      specific and not required for recruitment of actin.
AB  - Chlamydiae are obligate intracellular pathogens that efficiently induce their
      endocytosis by susceptible eukaryotic host cells. Recently, a Chlamydia
      trachomatis type III secreted effector protein, Tarp, was found to be
      translocated and tyrosine phosphorylated at the site of entry and associated with
      the recruitment of actin that coincides with endocytosis. C. trachomatis Tarp
      possesses up to six direct repeats of approximately 50 amino acids each. The
      majority of the tyrosine residues are found within this repeat region. Here we
      have ectopically expressed distinct domains of Tarp in HeLa 229 cells and
      demonstrated that tyrosine phosphorylation occurs primarily within the repeat
      region, while recruitment of actin is mediated by the C-terminal domain of the
      protein. A comparison of other sequenced chlamydial genomes revealed that each
      contains an ortholog of Tarp, although Chlamydia muridarum, Chlamydophila caviae,
      and Chlamydophila pneumoniae Tarp lack the large repeat region.
      Immunofluorescence and immunoblotting using an antiphosphotyrosine antibody show
      no evidence of phosphotyrosine at the site of entry of C. muridarum, C. caviae,
      and C. pneumoniae, although each species similarly recruits actin. Ectopic
      expression of full-length C. trachomatis and C. caviae Tarp confirmed that both
      recruit actin but only C. trachomatis Tarp is tyrosine phosphorylated. The data
      indicate that the C-terminal domain of Tarp is essential for actin recruitment
      and that tyrosine phosphorylation may not be an absolute requirement for actin
      recruitment. The results further suggest the potential for additional, unknown
      signal transduction pathways associated specifically with C. trachomatis.

PMID- 15972472
TI  - Listeriolysin O-induced membrane permeation mediates persistent interleukin-6
      production in Caco-2 cells during Listeria monocytogenes infection in vitro.
AB  - Listeriolysin O (LLO), a major virulence factor of Listeria monocytogenes, is a
      member of the cholesterol-dependent cytolysin family and plays important roles
      not only in survival of this bacterium in phagocytes but also in induction of
      various cellular responses, including cytokine production. In this work, we
      examined the involvement of LLO in induction of the cytokine response in
      intestinal epithelial cells, the front line of host defense against food-borne
      listeriosis. Infection of Caco-2 cells with wild-type L. monocytogenes induced
      persistent expression of interleukin-6 (IL-6) mRNA. In contrast, IL-6 expression
      was observed only transiently during infection with non-LLO-producing strains. A
      sublytic dose of recombinant LLO (rLLO) induced the expression of IL-6 via
      formation of membrane pores. Under conditions of LLO-induced pore formation
      without extensive cell lysis, Ca2+ influx was observed, and the IL-6 expression
      induced by rLLO was inhibited by pretreatment with 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), an
      intracellular Ca2+ chelator. LLO secreted by cytoplasmic L. monocytogenes
      appeared to induce pore formation in the membrane and to enable the trafficking
      of intracellular and extracellular molecules. Pretreatment with BAPTA-AM
      inhibited persistent IL-6 expression in Caco-2 cells infected with wild-type L.
      monocytogenes. These results suggest that LLO is involved in IL-6 production in
      the late phase of infection through the formation of Ca2+-permeable pores and
      subsequent Ca2+-dependent modulation of signaling and gene expression.

PMID- 15972473
TI  - Noninvasive biophotonic imaging for monitoring of catheter-associated urinary
      tract infections and therapy in mice.
AB  - Urinary tract infections (UTIs) are among the most common bacterial infections
      acquired by humans, particularly in catheterized patients. A major problem with
      catheterization is the formation of bacterial biofilms on catheter material and
      the risk of developing persistent UTIs that are difficult to monitor and
      eradicate. To better understand the course of UTIs and allow more accurate
      studies of in vivo antibiotic efficacy, we developed a catheter-based biofilm
      infection model with mice, using bioluminescently engineered bacteria. Two
      important urinary tract pathogens, Pseudomonas aeruginosa and Proteus mirabilis,
      were made bioluminescent by stable insertion of a complete lux operon. Segments
      of catheter material (precolonized or postimplant infected) with either pathogen
      were placed transurethrally in the lumen of the bladder by using a metal stylet
      without surgical manipulation. The bioluminescent strains were sufficiently
      bright to be readily monitored from the outside of infected animals, using a low
      light optical imaging system, including the ability to trace the ascending
      pattern of light-emitting bacteria through ureters to the kidneys. Placement of
      the catheter in the bladder not only resulted in the development of strong
      cystitis that persisted significantly longer than in mice challenged with
      bacterial suspensions alone but also required prolonged antibiotic treatment to
      reduce the level of infection. Treatment of infected mice for 4 days with
      ciprofloxacin at 30 mg/kg of body weight twice a day cured cystitis and renal
      infection in noncatheterized mice. Similarly, ciprofloxacin reduced the bacterial
      burden to undetectable levels in catheterized mice but did not inhibit rebound of
      the infection upon cessation of antibiotic therapy. This methodology easily
      allows spatial information to be monitored sequentially throughout the entire
      disease process, including ascending UTI, treatment efficacy, and relapse, all
      without exogenous sampling, which is not possible with conventional methods.

PMID- 15972474
TI  - Infection-stimulated fibrin deposition controls hemorrhage and limits hepatic
      bacterial growth during listeriosis.
AB  - Bacterial infections are major causes of human mortality. The activation of
      coagulation pathways leading to the deposition of insoluble fibrin frequently
      accompanies bacterial infection, and much attention has focused upon the
      pathological attributes of infection-stimulated fibrin deposition. Nevertheless,
      here we present conclusive evidence that infection-stimulated fibrin deposition
      can perform critical protective functions during bacterial infection.
      Specifically, we demonstrate that coagulation-impaired fibrin(ogen)-deficient
      mice, in comparison with genetically matched control mice, display increased
      mortality upon peritoneal infection with the gram-positive facultative
      intracellular bacterium Listeria monocytogenes. To distinguish effects of
      fibrinogen from those of fibrin, we treat wild-type mice with warfarin, an
      anticoagulant that suppresses fibrin formation without impacting fibrinogen
      levels. Warfarin treatment exacerbates listeriosis, suggesting that fibrin is the
      key mediator of protection. With regard to the underlying protective mechanisms,
      we demonstrate that fibrin(ogen) suppresses anemia, reduces hemorrhagic
      pathology, and limits bacterial growth during listeriosis. Despite confirming a
      prior report that fibrin(ogen) promotes the peritoneal clearance of the
      extracellular bacterium Staphylococcal aureus, we demonstrate that fibrin(ogen)
      plays little role in controlling peritoneal numbers of L. monocytogenes bacteria
      or the dissemination of L. monocytogenes bacteria from the peritoneal cavity.
      Rather, fibrin(ogen) primarily limits the growth of these intracellular bacteria
      within hepatic tissue. While the pathological potential of excessive infection
      stimulated fibrin deposition is well appreciated, our findings reveal that fibrin
      can function protectively, via multiple mechanisms, during bacterial infection.

PMID- 15972475
TI  - Trafficking pathways and characterization of CD4 and CD8 cells recruited to the
      skin of humans experimentally infected with Haemophilus ducreyi.
AB  - T-cell homing to infected skin is not well studied in humans. We examined sites
      experimentally infected with Haemophilus ducreyi by immunohistochemistry and flow
      cytometry for expression of receptors and ligands involved in cutaneous T-cell
      homing and determined the phenotypes of the T cells that trafficked to skin.
      Endothelial cells expressed E-selectin in infected but not uninfected skin, while
      peripheral node addressin (PNAd) was minimally expressed in all samples. CC
      chemokine ligand 27 (CCL27) was expressed in the epidermis and endothelium of
      both infected and uninfected skin. Interestingly, CCL21, a chemokine thought to
      be associated principally with T-cell trafficking in the lymphatic compartment,
      was highly expressed on the endothelium of infected skin. Few naive cells were
      present in experimental lesions, emphasizing the combined role of PNAd and CCL21
      in trafficking of this subset. Memory cells (CD45RA-) dominated both CD4 and CD8
      T-cell populations at the site of infection. Effector memory (CD45RA- CD27-) CD4+
      and CD8+ T cells were enriched in lesions. Although the CC chemokine receptor 7
      positive (CCR7+) population of both central memory (CD45RA- CD27+) and effector
      memory cells was not enriched in the skin compared to peripheral blood, CCR7+
      cells were not precluded from entering infected skin. Taken together with our
      previous work (D. Soler, T. L. Humphreys, S. M. Spinola, and J. J. Campbell,
      Blood 101:1677-1683, 2003), these studies led us to propose a model of memory T
      cell trafficking to skin in response to experimental H. ducreyi infection.

PMID- 15972477
TI  - Plasmodium falciparum merozoite surface protein 8 is a ring-stage membrane
      protein that localizes to the parasitophorous vacuole of infected erythrocytes.
AB  - To date, the following seven glycosylphosphatidylinositol (GPI)-anchored
      merozoite antigens have been described in Plasmodium falciparum: merozoite
      associated surface protein 1 (MSP-1), MSP-2, MSP-4, MSP-5, MSP-8, MSP-10, and the
      rhoptry-associated membrane antigen. Of these, MSP-1, MSP-8, and MSP-10 possess a
      double epidermal growth factor (EGF)-like domain at the C terminus, and these
      modules are considered potential targets of protective immunity. In this study,
      we found that surprisingly, P. falciparum MSP-8 is transcribed and translated in
      the ring stage and is absent from the surface of merozoites. MSP-8 is the only
      GPI-anchored protein known to be expressed at this time. It is synthesized as a
      mature 80-kDa protein which is rapidly processed to a C-terminal 17-kDa species
      that contains the double EGF module. As determined by a combination of
      immunofluorescence and membrane purification approaches, it appears likely that
      MSP-8 initially localizes to the parasite plasma membrane in the ring stage.
      Although the C-terminal 17-kDa fragment is present in more mature stages, at
      these times it is found in the food vacuole. We successfully disrupted the MSP-8
      gene in P. falciparum, a process that validated the specificity of the antibodies
      used in this study and also demonstrated that MSP-8 does not play a role
      essential to maintenance of the erythrocyte cycle. This finding, together with
      the observation that MSP-8 is exclusively intracellular, casts doubt over the
      viability of this antigen as a vaccine. However, it is still possible that MSP-8
      is involved in an early parasitophorous vacuole function that is significant for
      pathogenesis in the human host.

PMID- 15972476
TI  - Antagonizing deactivating cytokines to enhance host defense and chemotherapy in
      experimental visceral leishmaniasis.
AB  - In experimental visceral leishmaniasis, inhibition of interleukin 10 (IL-10)
      signaling enhances Th1-cell-associated responses, promoting gamma interferon (IFN
      gamma) secretion, granuloma assembly, macrophage activation with substantial
      liver parasite killing, and synergy with pentavalent antimony (Sb) chemotherapy.
      To determine if inhibiting other suppressive cytokines has similar therapeutic
      potential, Leishmania donovani-infected BALB/c mice were injected with anti-IL-4
      monoclonal antibody or receptor fusion antagonists of IL-13 or transforming
      growth factor beta (TGF-beta). Targeting IL-13 or TGF-beta enabled inhibition of
      L. donovani replication but little parasite killing; anti-IL-4 had no effect.
      None of the three antagonists promoted IFN-gamma production, granuloma
      maturation, or Sb efficacy. Excess IL-13 and TGF-beta exacerbated liver
      infection; however, effects were transient. Among IL-10, IL-4, IL-13, and TGF
      beta, cytokines capable of disabling Th1-cell mechanisms (including those which
      support chemotherapy), IL-10 appears to be the appropriate target for therapeutic
      inhibition in visceral L. donovani infection.

PMID- 15972478
TI  - Cellular immune suppressor activity resides in lymphocyte cell clusters adjacent
      to granulomata in human coccidioidomycosis.
AB  - The in situ immunologic response in human coccidioidomycosis remains undefined.
      To explore this further, pulmonary necrotizing coccidioidal granulomata were
      examined using immunohistochemical staining for lymphocyte subsets and for the
      cytokines interleukin-10 (IL-10) and gamma interferon (IFN-gamma). Discrete
      perigranulomatous lymphocytic clusters were seen in eight of nine tissues
      examined. In these tissues, T lymphocytes (CD3+) significantly outnumbered B
      lymphocytes (CD20+) in the mantle area of the granulomata (P = 0.028), whereas
      the clusters were composed of roughly equal numbers of T and B lymphocytes. While
      the number of cells in the mantle expressing IL-10 was similar to those in the
      perigranulomatous clusters, there were significantly more cells expressing IFN
      gamma in the mantle than in the clusters (P = 0.037). Confocal microscopy
      revealed that CD4+ T lymphocytes and B lymphocytes are associated with IL-10
      production. CD4+CD25+ T lymphocytes were identified in the perigranulomatous
      clusters but were not associated with IL-10 production. This is the first report
      noting perigranulomatous lymphocyte clusters and IL-10 in association with human
      coccidioidal granulomata and suggests that down-regulation of the cellular immune
      response is occurring within coccidioidal granulomata.

PMID- 15972479
TI  - Local peroxynitrite formation contributes to early control of Cryptosporidium
      parvum infection.
AB  - In intestinal inflammation, mucosal injury is often exacerbated by the reaction
      of NO with neutrophil-derived superoxide to form the potent oxidant
      peroxynitrite. Peroxynitrite also has antimicrobial properties that aid in the
      killing mechanism of macrophages and neutrophils. Cryptosporidium parvum
      parasitizes intestinal epithelium, resulting in loss of epithelial cells and
      mucosal inflammation. Synthesis of NO is significantly increased and arises from
      the induced expression of inducible nitric oxide synthase (iNOS) by the infected
      epithelium. Inhibition of iNOS results in intensified epithelial parasitism and
      oocyst excretion. We hypothesized that formation of peroxynitrite is restricted
      to sites of iNOS expression by the epithelium and contributes to host defense in
      C. parvum infection. Accordingly, the location and biological effects of
      peroxynitrite formation were examined in neonatal piglets infected with C.
      parvum. Infected piglets were treated daily with a selective iNOS inhibitor [L-N6
      (1-iminoethyl)-lysine] or one of two peroxynitrite scavengers [5,10,15,20
      tetrakis(N-methyl-4'-pyridyl)porphyrinato iron(III) or uric acid] or received
      vehicle. At peak infection, peroxynitrite formation was restricted to sites of
      iNOS expression by parasitized epithelium and lamina propria of the apical villi.
      Peroxynitrite formation was dependent on iNOS activity and was inhibited by
      treatment with peroxynitrite scavengers. Scavengers increased the number of
      intracellular parasites and the number of infected epithelial cells present per
      villus and significantly exacerbated oocyst excretion. Recovery from infection
      was not delayed by ongoing treatment with scavenger. The present results are the
      first to demonstrate an in vivo role for peroxynitrite formation in acute mucosal
      defense against a noninvasive intestinal epithelial pathogen.

PMID- 15972480
TI  - Survival of Salmonella enterica serovar Typhimurium within late endosomal
      lysosomal compartments of B lymphocytes is associated with the inability to use
      the vacuolar alternative major histocompatibility complex class I antigen
      processing pathway.
AB  - Gamma interferon (IFN-gamma)-activated macrophages use an alternative processing
      mechanism to present Salmonella antigens to CD8(+) T lymphocytes. This pathway
      involves processing of antigen in a vacuolar compartment followed by secretion
      and loading of antigenic peptides to major histocompatibility complex class I
      (MHC-I) molecules on macrophage cell surface and bystander cells. In this study,
      we have shown that B lymphocytes are not able to process Salmonella antigens
      using this alternative pathway. This is due to differences in Salmonella enterica
      serovar Typhimurium-containing vacuoles (SCV) when comparing late endosomal
      lysosomal processing compartments in B lymphocytes to those in macrophages. The
      IFN-gamma-activated IC21 macrophage cell line and A-20 B-cell line were infected
      with live or dead Salmonella enterica serovar Typhimurium. The SCV in B cells
      were in a late endosomal-lysosomal compartment, whereas SCV in macrophages were
      remodeled to a non-characteristic late endosomal-lysosomal compartment over time.
      Despite the difference in SCV within macrophages and B lymphocytes, S. enterica
      serovar Typhimurium survives more efficiently within the IFN-gamma-activated B
      cells than in activated macrophage cell lines. Similar results were found during
      in vivo acute infection. We determined that a lack of remodeling of late
      endosomal-lysosomal compartments by live Salmonella infection in B lymphocytes is
      associated with the inability to use the alternative MHC-I antigen-processing
      pathway, providing a survival advantage to the bacterium. Our data also suggest
      that the B lymphocyte late endosome-lysosome environment allows the expression of
      Salmonella virulence mechanisms favoring B lymphocytes in addition to macrophages
      and dendritic cells as a reservoir during in vivo infection.

PMID- 15972481
TI  - Intranasal administration of recombinant Neisseria gonorrhoeae transferrin
      binding proteins A and B conjugated to the cholera toxin B subunit induces
      systemic and vaginal antibodies in mice.
AB  - The transferrin binding proteins (TbpA and TbpB) comprise the gonococcal
      transferrin receptor and are considered potential antigens for inclusion in a
      vaccine against Neisseria gonorrhoeae. Intranasal (IN) immunization has shown
      promise in development of immunity against sexually transmitted disease
      pathogens, in part due to the induction of antigen-specific genital tract
      immunoglobulin A (IgA) and IgG. Conjugation of antigens to the highly immunogenic
      cholera toxin B subunit (Ctb) enhances antibody responses in the serum and
      mucosal secretions following IN vaccination. In the current study, we
      characterized the anti-Tbp immune responses following immunization of mice IN
      with recombinant transferrin binding proteins (rTbpA and rTbpB) conjugated to
      rCtb. We found that both rTbpA-Ctb and rTbpB-Ctb conjugates administered IN
      induced antibody responses in the serum and genital tract. IN immunization
      resulted in both IgA and IgG in the genital tract; however, subcutaneous
      immunization mainly generated IgG. Surprisingly, rTbpA alone was immunogenic and
      induced serum and mucosal antibody responses similar to those elicited against
      the rTbpA-Ctb conjugate. Overall, rTbpB was much more immunogenic than rTbpA,
      generating serum IgG levels that were greater than those elicited against rTbpA.
      Bactericidal assays conducted with sera collected from mice immunized IN with
      TbpA and/or TbpB indicated that both antigens generated antibodies with
      bactericidal activity. Anti-TbpA antibodies were cross-bactericidal against
      heterologous gonococcal strains, whereas TbpB-specific antibodies were less cross
      reactive. By contrast, antibodies elicited via subcutaneous immunization were not
      cross-bactericidal against heterologous strains, indicating that IN vaccination
      could be the preferred route for elicitation of biologically functional
      antibodies.

PMID- 15972482
TI  - Development of secondary inclusions in cells infected by Chlamydia trachomatis.
AB  - The chlamydiae are obligate intracellular bacteria that occupy a non-acidified
      vacuole (the inclusion) during their entire developmental cycle. These bacteria
      produce a set of proteins (Inc proteins) that localize to the surface of the
      inclusion within infected cells. Chlamydia trachomatis IncA is also commonly
      found in long fibers that extend away from the inclusion. We used standard and
      confocal immunofluorescence microscopy to demonstrate that these fibers extend to
      newly developed inclusions, termed secondary inclusions, within infected cells.
      Secondary inclusions observed at early time points postinfection were devoid of
      chlamydial reticulate bodies. Later in the developmental cycle, secondary
      inclusions containing variable numbers of reticulate bodies were common.
      Reticulate bodies were also observed within the IncA-laden fibers connecting
      primary and secondary inclusions. Quantitative differences in secondary inclusion
      formation were found among clinical isolates, and these differences were
      associated with serovar. Isolates of serovar G consistently produced secondary
      inclusions at the highest frequency (P < 0.0001). Similar quantitative studies
      demonstrated that secondary inclusion formation was associated with segregation
      of inclusions to daughter cells following cytokinesis. We conclude that the
      production of secondary inclusions via IncA-laden fibers allows chlamydiae to
      generate an expanded intracellular niche in which they can grow and may provide a
      means for continuous infection within progeny cells following cell division.

PMID- 15972483
TI  - posttranslational modification of recombinant Plasmodium falciparum apical
      membrane antigen 1: impact on functional immune responses to a malaria vaccine
      candidate.
AB  - Recombinant apical membrane antigen 1 (AMA1) is a leading vaccine candidate for
      Plasmodium falciparum malaria, as antibodies against recombinant P. falciparum
      AMA1 (PfAMA1) interrupt merozoite invasion into erythrocytes. In order to
      investigate the role of posttranslational modification in modulating the
      functional immune response to recombinant AMA1, two separate alleles of PfAMA1
      (FVO and 3D7), in which native N-glycosylation sites have been mutated, were
      produced using Escherichia coli and a Pichia pastoris expression system.
      Recombinant Pichia pastoris AMA1-FVO (PpAMA1-FVO) and PpAMA1-3D7 are O-linked
      glycosylated, and 45% of PpAMA1-3D7 is nicked, though all four recombinant
      molecules react with conformation-specific monoclonal antibodies. To address the
      immunological effect of O-linked glycosylation, we compared the immunogenicity of
      E. coli AMA1-FVO (EcAMA1-FVO) and PpAMA1-FVO antigens, since both molecules are
      intact. The effect of antigen nicking was then investigated by comparing the
      immunogenicity of EcAMA1-3D7 and PpAMA1-3D7. Our data demonstrate that there is
      no significant difference in the rabbit antibody titer elicited towards EcAMA1
      FVO and PpAMA1-FVO or to EcAMA1-3D7 and PpAMA1-3D7. Furthermore, we have
      demonstrated that recombinant AMA1 (FVO or 3D7), whether expressed and refolded
      from E. coli or produced from the Pichia expression system, is equivalent and
      mimics the functionality of the native protein in in vitro growth inhibition
      assay experiments. We conclude that in the case of recombinant AMA1, the E. coli-
      and P. pastoris-derived antigens are immunologically and functionally equivalent
      and are unaffected by the posttranslational modification resulting from
      expression in these two systems.

PMID- 15972484
TI  - Inactivation of vimF, a putative glycosyltransferase gene downstream of vimE,
      alters glycosylation and activation of the gingipains in Porphyromonas gingivalis
      W83.
AB  - Regulation/activation of the Porphyromonas gingivalis gingipains is poorly
      understood. A 1.2-kb open reading frame, a putative glycosyltransferase,
      downstream of vimE, was cloned, insertionally inactivated using the ermF-ermAM
      antibiotic resistance cassette, and used to create a defective mutant by allelic
      exchange. In contrast to the wild-type W83 strain, this mutant, designated P.
      gingivalis FLL95, was nonpigmented and nonhemolytic when plated on Brucella blood
      agar. Arginine- and lysine-specific gingipain activities were reduced by
      approximately 97% and 96%, respectively, relative to that of the parent strain.
      These activities were unaffected by the growth phase, in contrast to the vimA
      defective mutant P. gingivalis FLL92. Expression of the rgpA, rgpB, and kgp
      gingipain genes was unaffected in P. gingivalis FLL95 in comparison to the wild
      type strain. In nonactive gingipain extracellular protein fractions, multiple
      high-molecular-weight proteins immunoreacted with gingipain-specific antibodies.
      The specific gingipain-associated sugar moiety recognized by monoclonal antibody
      1B5 was absent in FLL95. Taken together, these results suggest that the vimE
      downstream gene, designated vimF (virulence modulating gene F), which is a
      putative glycosyltransferase group 1, is involved in the regulation of the major
      virulence factors of P. gingivalis.

PMID- 15972485
TI  - Short fimbriae of Porphyromonas gingivalis and their role in coadhesion with
      Streptococcus gordonii.
AB  - Porphyromonas gingivalis, one of the causative agents of adult periodontitis,
      attaches and forms biofilms on substrata of Streptococcus gordonii. Coadhesion
      and biofilm development between these organisms requires the interaction of the
      short fimbriae of P. gingivalis with the SspB streptococcal surface polypeptide.
      In this study we investigated the structure and binding activities of the short
      fimbriae of P. gingivalis. Electron microscopy showed that isolated short
      fimbriae have an average length of 103 nm and exhibit a helical structure with a
      pitch of ca. 27 nm. Mfa1, the major protein subunit of the short fimbriae, bound
      to SspB protein, and this reaction was inhibited by purified recombinant Mfa1 and
      monospecifc anti-Mfa1 serum in a dose-dependent manner. Complementation of a
      polar Mfa1 mutant with the mfa1 gene restored the coadhesion phenotype of P.
      gingivalis. Hence, the Mfa1 structural fimbrial subunit does not require
      accessory proteins for binding to SspB. Furthermore, the interaction of Mfa1 with
      SspB is necessary for optimal coadhesion between P. gingivalis and S. gordonii.

PMID- 15972486
TI  - Role of mitogen-activated protein kinases and NF-kappaB in the regulation of
      proinflammatory and anti-inflammatory cytokines by Porphyromonas gingivalis
      hemagglutinin B.
AB  - Hemagglutinin B (HagB) is a nonfimbrial adhesin expressed on the surface of
      Porphyromonas gingivalis and has been implicated as a potential virulence factor
      involved in mediating the attachment of the bacteria to host cells. However, the
      molecular mechanisms underlying host responses to HagB and their roles in
      pathogenesis have yet to be elucidated. Mitogen-activated protein kinases (MAPKs)
      are activated following engagement of a variety of cell surface receptors via
      dual tyrosine and threonine phosphorylation and are thought to be involved in
      various cellular responses. The purpose of this study was to determine the role
      of intracellular signaling pathways including the MAPKs and NF-kappaB in
      regulating the production of proinflammatory and anti-inflammatory cytokines
      following stimulation of murine macrophages with recombinant HagB (rHagB).
      Stimulation of peritoneal macrophages with rHagB resulted in the production of
      the proinflammatory cytokines interleukin-12p40 (IL-12p40), gamma interferon (IFN
      gamma), and tumor necrosis factor alpha, as well as the anti-inflammatory
      cytokine IL-10. We also demonstrated the activation of extracellular signal
      related kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), and p38 MAPKs by
      rHagB-stimulated macrophages. Furthermore, blocking of the ERK and p38 signaling
      pathways by using specific inhibitors revealed differential regulatory roles in
      the rHagB-mediated production of proinflammatory and anti-inflammatory cytokines.
      ERK and p38 were important in down-regulation of IL-12p40 and IFN-gamma
      production and up-regulation of IL-10 production. The enhanced levels of IL-12p40
      in rHagB-stimulated macrophages by inhibition of ERK or p38 activity were
      partially attributable to the inhibition of IL-10 production. Moreover, NF-kappaB
      was found to be critical for up-regulation of IL-12p40 and down-regulation of IL
      10 production in rHagB-stimulated macrophages. Taken together, our results
      demonstrate a role for the p38 and ERK pathways and the transcription factor NF
      kappaB in modulating key immunoregulatory cytokines involved in the development
      of immune responses to P. gingivalis HagB.

PMID- 15972487
TI  - Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia
      coli.
AB  - Urinary tract infections are most commonly caused by uropathogenic strains of
      Escherichia coli (UPEC), which invade superficial bladder epithelial cells via a
      type 1 pilus-dependent mechanism. Inside these epithelial cells, UPEC organisms
      multiply to high numbers to form intracellular bacterial communities, allowing
      them to avoid immune detection. Bladder epithelial cells produce interleukin-6
      (IL-6) and IL-8 in response to laboratory strains of E. coli in vitro. We
      investigated the ability of UPEC to alter epithelial cytokine signaling by
      examining the in vitro responses of bladder epithelial cell lines to the cystitis
      strains UTI89 and NU14. The cystitis strains induced significantly less IL-6 than
      did the laboratory E. coli strain MG1655 from 5637 and T24 bladder epithelial
      cells. The cystitis strains also suppressed epithelial cytokine responses to
      exogenous lipopolysaccharide (LPS) and to laboratory E. coli. We found that
      insertional mutations in the rfa and rfb operons and in the surA gene all
      abolished the ability of UTI89 to suppress cytokine induction. The rfa and rfb
      operons encode LPS biosynthetic genes, while surA encodes a periplasmic cis-trans
      prolyl isomerase important in the biogenesis of outer membrane proteins. We
      conclude that, in this in vitro model system, cystitis strains of UPEC have genes
      encoding factors that suppress proinflammatory cytokine production by bladder
      epithelial cells.

PMID- 15972488
TI  - Involvement of up-regulated CXC chemokine ligand 16/scavenger receptor that binds
      phosphatidylserine and oxidized lipoprotein in endotoxin-induced lethal liver
      injury via regulation of T-cell recruitment and adhesion.
AB  - A murine model of endotoxin-induced lethal liver injury induced by Mycobacterium
      bovis BCG plus lipopolysaccharide (LPS) has been widely accepted and used. It has
      been reported that T cells play an important role in the pathogenesis of liver
      damage in this model. However, the precise mechanisms involved in regulation of
      the trafficking of effector T cells need to be elucidated. In the present study,
      we first reported that CXCL16/SR-PSOX (CXC chemokine ligand 16/scavenger receptor
      that binds phosphatidylserine and oxidized lipoprotein), a chemokine containing
      both membrane-anchored and soluble forms, was strongly up-regulated and
      predominantly distributed in the vascular endothelium in the injured liver tissue
      in the model. The secretory and membrane-anchored CXCL16/SR-PSOX functioned as a
      chemokine and an adhesive molecule, respectively, to attract T cells to a tumor
      necrosis factor alpha-activated endothelial cell line (SVEC) in vitro. To further
      identify the pathophysiological roles of CXCL16/SR-PSOX in the liver injury, the
      anti-CXCL16 antibody was administered to the BCG-primed mice before LPS challenge
      in vivo. Significant protection effects were observed with 70% of mice regarding
      lethality, the massive necrosis in the liver was reduced, and the intrahepatic
      infiltrating T cells were significantly inhibited. Taken together, these findings
      strongly suggest that functional CXCL16/SR-PSOX, as both a chemokine and an
      adhesion molecule, may be involved in the pathogenesis of the endotoxin-induced
      lethal liver injury via recruitment and adhesion of activated T cells to the
      vascular endothelium.

PMID- 15972489
TI  - Activation of lipid metabolism contributes to interleukin-8 production during
      Chlamydia trachomatis infection of cervical epithelial cells.
AB  - Chlamydia trachomatis infection is the most common cause of bacterial sexually
      transmitted diseases. Infection of the urogenital tract by C. trachomatis causes
      chronic inflammation and related clinical complications. Unlike other invasive
      bacteria that induce a rapid cytokine/chemokine production, chlamydial infection
      induces delayed inflammatory response and proinflammatory chemokine production
      that is dependent on bacterial growth. We present data here to show that the
      lipid metabolism required for chlamydial growth contributes to Chlamydia-induced
      proinflammatory chemokine production. By gene microarray profiling, validated
      with biochemical studies, we found that C. trachomatis LGV2 selectively
      upregulated PTGS2 (COX2) and PTGER4 (EP4) in cervical epithelial HeLa 229 cells.
      COX2 is an enzyme that catalyzes the rate-limiting step of arachidonic acid
      conversion to prostaglandins, including prostaglandin E2 (PGE2) and other
      eicosanoids, whereas EP4 is a subtype of cell surface receptors for PGE2. We show
      that Chlamydia infection induced COX2 protein expression in both epithelial cells
      and peripheral blood mononuclear cells and promoted PGE2 release. Exogenous PGE2
      was able to induce interleukin-8 release in HeLa 229 epithelial cells. Finally,
      we demonstrated that interleukin-8 induction by Chlamydia infection or PGE2
      treatment was dependent on extracellular signal-regulated kinase/mitogen
      activated protein activity. Together, these data demonstrate that the host lipid
      remodeling process required for chlamydial growth contributes to proinflammatory
      chemokine production. This study also highlights the importance of maintaining a
      balanced habitat for parasitic pathogens as obligate intracellular organisms.

PMID- 15972490
TI  - Identification of novel genes in intestinal tissue that are regulated after
      infection with an intestinal nematode parasite.
AB  - Infection of resistant or susceptible mice with Trichuris muris provokes
      mesenteric lymph node responses which are polarized towards Th2 or Th1,
      respectively. These responses are well documented in the literature. In contrast,
      little is known about the local responses occurring within the infected
      intestine. Through microarray analyses, we demonstrate that the gene expression
      profile of infected gut tissue differs according to whether the parasite is
      expelled or not. Genes differentially regulated postinfection in resistant BALB/c
      mice include several antimicrobial genes, in particular, intelectin (Itln). In
      contrast, analyses in AKR mice which ultimately progress to chronic infection
      provide evidence for a Th1-dominated mucosa with up-regulated expression of genes
      regulated by gamma interferon. Increases in the expression of genes associated
      with tryptophan metabolism were also apparent with the coinduction of
      tryptophanyl tRNA synthetase (Wars) and indoleamine-2,3-dioxygenase (Indo). With
      the emerging literature on the role of these gene products in the suppression of
      T-cell responses in vitro and in vivo, their up-regulated expression here may
      suggest a role for tryptophan metabolism in the parasite survival strategy.

PMID- 15972491
TI  - Regulatory T cells modulate Th2 responses induced by Brugia pahangi third-stage
      larvae.
AB  - Infection of BALB/c mice with Brugia pahangi third-stage larvae (L3) results in
      the production of interleukin-4 (IL-4), IL-5, and IL-10 with a resultant down
      regulation in Th1 responses. Previously, this was thought to reflect a skewing of
      immune responses towards a Th2 phenotype by the infective stage of the parasite.
      In this study, we show that exposure to the L3 of Brugia also induces the
      expansion of a population of CD4 cells that express CD25 and cytotoxic-T
      lymphocyte-associated antigen 4 in an IL-4-independent fashion. By quantitative
      reverse transcription-PCR, we show that the CD25+ population is highly enriched
      in mRNA for the Foxp3 transcription factor and that these cells express
      significantly more IL-10 mRNA than the CD25- population, suggesting a likely
      regulatory phenotype. The functional capacity of these cells was demonstrated
      using a neutralizing CD25 monoclonal antibody (MAb). Mice treated with this MAb
      demonstrated elevated levels of antigen (Ag)-specific proliferation in vitro, and
      levels of Ag-specific Th2 cytokines were significantly increased. These results
      suggest a complex network of regulation in L3-infected mice with Th2 cells
      limiting the Th1 response, while T-regulatory cells modulate Th2 responses.

PMID- 15972492
TI  - Oral spore vaccine based on live attenuated nontoxinogenic Bacillus anthracis
      expressing recombinant mutant protective antigen.
AB  - An attenuated nontoxinogenic nonencapsulated Bacillus anthracis spore vaccine
      expressing high levels of recombinant mutant protective antigen (PA), which upon
      subcutaneous immunization provided protection against a lethal B. anthracis
      challenge, was found to have the potential to serve also as an oral vaccine.
      Guinea pigs immunized per os with the recombinant spore vaccine were primed to B.
      anthracis vegetative antigens as well as to PA, yet only a fraction of the
      animals (30% to 50%) mounted a humoral response to all of these antigens.
      Protective immunity provided by per os immunization correlated with a threshold
      level of PA neutralizing antibody titers and was long-lasting. Protection
      conferred by per os immunization was attained when the vaccine was administered
      in the sporogenic form, which, unlike the vegetative cells, survived passage
      through the gastrointestinal tract. A comparison of immunization of unirradiated
      spores with immunization of gamma-irradiated spores demonstrated that germination
      and de novo synthesis of PA were prerequisites for mounting an immune protective
      response. Oral immunization of guinea pigs with attenuated B. anthracis spores
      resulted in a characteristic anti-PA immunoglobulin isotype profile
      (immunoglobulin [G1 IgG1] versus IgG2), as well as induction of specific anti-PA
      secretory IgA, indicating development of mucosal immunity.

PMID- 15972493
TI  - Characterization of a human monoclonal antibody against Shiga toxin 2 expressed
      in Chinese hamster ovary cells.
AB  - Shiga toxin-producing Escherichia coli infections can often lead to the
      development of hemolytic-uremic syndrome (HUS) in a small percentage of infected
      humans. Patients with HUS receive only supportive treatment as the benefit of
      antibiotic therapy remains uncertain. We have previously reported the generation
      and preclinical evaluation of neutralizing human monoclonal antibodies (HuMAbs)
      against the Shiga toxins (Stx). In this paper, we describe the expression in
      Chinese hamster ovary (CHO) cells of 5C12 HuMAb, which is directed against the A
      subunit of Stx2. The cDNAs of the light and heavy chain immunoglobulin (Ig)
      variable regions of 5C12 HuMAb were isolated and cloned into an expression vector
      containing human IgG1 constant regions. The vector was transfected into CHO
      cells, and transfectants secreting Stx2-specific antibody were screened by an
      Stx2-specific enzyme-linked immunosorbent assay. The CHO-produced recombinant
      5C12 (r5C12) showed similar specificity and binding affinity to Stx2 as the
      parent hybridoma-produced 5C12. More significantly, the r5C12 displayed the same
      neutralizing activity as the parent 5C12 in vitro and in vivo. In the mouse
      toxicity model, both antibodies significantly and equally prolonged survival at a
      dose of 0.312 microg/mouse. The data showed that since r5C12, produced in CHO
      cells, was equally effective as the parent 5C12, it is our choice candidate as a
      potential prophylactic or therapeutic agent against hemolytic-uremic syndrome.

PMID- 15972494
TI  - Protection against Leptospira interrogans sensu lato challenge by DNA
      immunization with the gene encoding hemolysin-associated protein 1.
AB  - The use of DNA constructs encoding leptospiral proteins is a promising new
      approach for vaccination against leptospirosis. In previous work we determined
      that immunization with hemolysis-associated protein 1 (Hap1) (LipL32) expressed
      by adenovirus induced significant protection against a virulent Leptospira
      challenge in gerbils. To avoid the use of the adenovirus vector, we checked for
      clinical protection against lethal challenge by DNA vaccination. A DNA vaccine
      expressing Hap1 was designed to enhance the direct gene transfer of this protein
      into gerbils. A challenge was performed 3 weeks after the last immunization with
      a virulent strain of serovar canicola. Our results show that the cross-protective
      effect with pathogenic strains of Leptospira, shared by Hap1, could be mediated
      by the DNA plasmid vector. This finding should facilitate the design and
      development of a new generation of vaccines against bacteria, particularly
      Leptospira interrogans sensu lato.

PMID- 15972495
TI  - Characterization of native outer membrane vesicles from lpxL mutant strains of
      Neisseria meningitidis for use in parenteral vaccination.
AB  - Native outer membrane vesicles (NOMV) of Neisseria meningitidis consist of intact
      outer membrane and contain outer membrane proteins (OMP) and lipooligosaccharides
      (LOS) in their natural conformation and membrane environment. NOMV have been
      safely used intranasally in P1 studies with encouraging results, but they are too
      toxic for parenteral vaccination. We now report the preparation and
      characterization of lpxL mutants that express LOS with reduced toxicity, and the
      evaluation of the potential of NOMV from these strains for use as a parenteral
      vaccine. A series of deletion mutants were prepared with knockouts of one or more
      of the lpxL1, lpxL2, or synX genes. The deltalpxL2 mutants had a reduced growth
      rate, reduced level of LOS expression, and increased sensitivity to surfactants.
      In addition, deltasynX deltalpxL2 double mutants had reduced viability in
      stationary phase. The deltalpxL1 deltalpxL2 double mutant behaved essentially the
      same as the deltalpxL2 single mutant. LOS from both lpxL mutant strains exhibited
      altered migration on polyacrylamide gels. The LOS of deltalpxL2 mutants of L3,7
      strains were fully sialylated. NOMV prepared from lpxL2 mutants was about 200
      fold less active than wild-type NOMV in rabbit pyrogen tests and in tumor
      necrosis factor alpha release assays. Bactericidal titers induced in animals by
      deltalpxL2 mutant NOMV were lower than those induced by deltalpxL1 or wild-type
      NOMV. However, immunogenicity could be largely restored by use of an adjuvant.
      These results provide evidence that NOMV from deltalpxL2 mutant strains will be
      safe and immunogenic in humans when given parenterally.

PMID- 15972496
TI  - Multiple insertional events, restricted by the genetic background, have led to
      acquisition of pathogenicity island IIJ96-like domains among Escherichia coli
      strains of different clinical origins.
AB  - We investigated the dissemination of pathogenicity island (PAI) II(J96)-like
      elements (hra, hly, cnf1, and pap) among 455 Escherichia coli isolates from
      children and adults with urinary tract infection (UTI), neonates with meningitis
      or colonized healthy neonates, and 74 reference strains by means of PCR
      phylogenetic grouping, ribotyping, and PCR analysis of virulence genes.
      Colocalization of these genes was documented by pulsed-field gel electrophoresis
      followed by Southern hybridization and long-range PCR (LRPCR) between the hra and
      the papG alleles. Site-specific insertion of the PAI was determined by LRPCR
      between hra and tRNA flanking sequences. hra, hly, and cnf1 were found in 113
      isolates and consistently colocalized, constituting the backbone of PAI II(J96)
      like domains. The prevalence of PAI II(J96)-like domains was significantly higher
      among UTI isolates than among neonatal meningitis and commensal isolates. These
      domains were restricted to a few ribotypes of group B2. In contrast to the
      consistent colocalization of hra, hly, and cnf1, the pap operon was varied: 12%
      of strains exhibited an allelic exchange of the papG class III allele (papGIII)
      for the papG class II allele (papGII) (only UTI isolates), and the pap operon was
      deleted in 23% of strains. No strains harbored papGIII outside the PAI, which
      appears to be the only source of this allele. PAI II(J96)-like domains were
      inserted in the vicinities of three different tRNAs--pheU (54%), leuX (29%), and
      pheV (15%)--depending on the genetic backgrounds and origins of the isolates.
      Multiple insertional events restricted by the genetic background have thus led to
      PAI II(J96) acquisition. Specific genetic backgrounds and insertion sites may
      have played a role in additional recombination processes for E. coli adaptation
      to different ecological niches.

PMID- 15972497
TI  - Nontoxic Shiga toxin derivatives from Escherichia coli possess adjuvant activity
      for the augmentation of antigen-specific immune responses via dendritic cell
      activation.
AB  - Shiga toxin (Stx) derivatives, such as the Stx1 B subunit (StxB1), which mediates
      toxin binding to the membrane, and mutant Stx1 (mStx1), which is a nontoxic
      doubly mutated Stx1 harboring amino acid substitutions in the A subunit, possess
      adjuvant activity via the activation of dendritic cells (DCs). Our results showed
      that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced
      expression of CD86, CD40, and major histocompatibility complex (MHC) class II
      molecules and, to some extent, also enhanced the expression of CD80 on bone
      marrow-derived DCs. StxB1-treated DCs exhibited an increase in tumor necrosis
      factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T
      cell proliferation, and the production of both Th1 and Th2 cytokines, including
      gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, and IL-10. When mice were given
      StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II
      expression by splenic DCs, were enhanced. The subcutaneous immunization of mice
      with ovalbumin (OVA) plus mStx1 or StxB1 induced high titers of OVA-specific
      immunoglobulin M (IgM), IgG1, and IgG2a in serum. OVA-specific CD4+ T cells
      isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-gamma, IL
      4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and
      Th2-type responses. Importantly, mice immunized subcutaneously with tetanus
      toxoid plus mStx1 or StxB1 were protected from a lethal challenge with tetanus
      toxin. These results suggest that nontoxic Stx derivatives, including both StxB1
      and mStx1, could be effective adjuvants for the induction of mixed Th-type CD4+ T
      cell-mediated antigen-specific antibody responses via the activation of DCs.

PMID- 15972498
TI  - Expression of the nfa1 gene cloned from pathogenic Naegleria fowleri in
      nonpathogenic N. gruberi enhances cytotoxicity against CHO target cells in vitro.
AB  - The pathogenic amoeba Naegleria fowleri has a 360-bp nfa1 gene that encodes the
      Nfa1 protein (13.1 kDa), which is located in the pseudopodia of the amoeba, and
      an anti-Nfa1 antibody reduces N. fowleri-induced mammalian-cell cytotoxicity in
      vitro. In contrast, an anti-Nfa1 antibody cannot detect Nfa1 protein expression
      in the nonpathogenic amoeba Naegleria gruberi, which also possesses the nfa1
      gene. In the present study, the nfa1 gene cloned from pathogenic N. fowleri was
      transfected into nonpathogenic N. gruberi to determine whether it was related to
      pathogenicity. The nfa1 gene was initially inserted into a eukaryotic
      transfection vector, pEGFP-C2, containing a cytomegalovirus promoter and the
      green fluorescent protein (GFP) gene, and was designed as pEGFP-C2/nfa1UTR
      (nfa1UTR contains 5' upstream regions, the nfa1 open reading frame, and 3'
      downstream regions). After transfection, the green fluorescence was observed in
      the cytoplasm of N. gruberi trophozoites. These transfectants were preserved for
      more than 9 months after selection. The transfected nfa1 gene was observed by PCR
      using nfa1- and vector-specific primers in the genomic DNA of N. gruberi
      transfected with the pEGFP-C2/nfa1UTR vector. In addition, the nfa1 and GFP genes
      were identified by reverse transcription-PCR in transgenic N. gruberi. The Nfa1
      protein expressed in transgenic N. gruberi was identified as a 13.1-kDa band by
      Western blotting using an anti-Nfa1 antibody. Finally, N. gruberi transfected
      with the pEGFP-C2/nfa1UTR vector was found to have enhanced cytotoxicity against
      CHO cells compared with naive N. gruberi.

PMID- 15972499
TI  - Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not
      explain the protective effect of helminth infections against atopy.
AB  - One hypothesis for the decreased rates of atopy observed among helminth-infected
      individuals is that parasite-induced polyclonal immunoglobulin E (IgE) out
      competes allergen-specific IgE for FcepsilonRI binding on basophils and mast
      cells. In experiments with fresh blood drawn from filaria-infected patients, we
      found no association between ratios of polyclonal to Brugia malayi antigen (BmAg)
      specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by
      histamine release. Using serum samples from a filaria-infected patient who also
      had dust mite (Dermatophagoides pteronyssinus)-specific IgE antibodies from time
      points with various ratios of polyclonal to D. pteronyssinus-specific IgE (16:1
      to 86:1), we demonstrated that increased ratios of polyclonal to D. pteronyssinus
      specific IgE did not attenuate basophil sensitization as measured by D.
      pteronyssinus-specific histamine release. Suppression of histamine release was
      likely not observed in either of these sets of experiments because polyclonal to
      antigen-specific IgE ratios were not sufficiently high, as concurrent passive
      sensitization of basophil experiments required ratios of polyclonal to antigen
      specific IgE of greater than 500:1 to suppress basophil histamine release.
      Further, the intensity of IgE staining in basophil populations from 20 patients
      with active filaria infections correlated strongly with total serum IgE levels
      (rho = 0.698; P = 0.0024) with no plateau in intensity of IgE staining, even
      though some patients had total IgE levels of greater than 10,000 ng/ml. Our data
      therefore suggest that in helminth infections (and in filarial infections in
      particular), the ratios of polyclonal to allergen-specific IgE rarely reach those
      levels necessary to inhibit allergen-specific IgE-FcepsilonRI binding and to
      suppress allergen-induced degranulation of mast cells and basophils.

PMID- 15972500
TI  - Effects of pregnancy and intensity of Plasmodium falciparum transmission on
      immunoglobulin G subclass responses to variant surface antigens.
AB  - Placenta-sequestering Plasmodium falciparum involved in the pathogenesis of
      pregnancy-associated malaria (PAM) in otherwise clinically immune women expresses
      particular variant surface antigens (VSA(PAM)) on the surface of infected
      erythrocytes that differ from VSA found in parasitized nonpregnant individuals
      (non-PAM type VSA). We studied levels of immunoglobulin G (IgG) and IgG
      subclasses with specificity for VSA(PAM) and for non-PAM type VSA in pregnant and
      nonpregnant women from two sites with different endemicities in Cameroon. We
      found that VSA(PAM)-specific responses depended on the pregnancy status, parity,
      gestational age, and parasite transmission intensity, whereas only the parasite
      transmission intensity influenced the levels of IgG specific for non-PAM type
      VSA. For both types of VSA, the responses were dominated by the cytophilic
      subclass IgG1, followed by IgG3. In pregnant women, the levels of VSA(PAM)
      specific antibodies either were very low or negative or were very high, whereas
      the levels of the antibodies specific for non-PAM type VSA were uniformly high.
      Interestingly, the levels of VSA(PAM)-specific IgG1 increased with increasing
      gestational age, while the levels of the corresponding IgG3 tended to decrease
      with increasing gestational age. The IgG subclass responses with specificity for
      non-PAM type VSA did not vary significantly with gestational age. Taken together,
      our data indicate that IgG1 and to a lesser extent IgG3 are the main subclasses
      involved in acquired VSA(PAM)-specific immunity to pregnancy-associated malaria.

PMID- 15972501
TI  - Thymidine-dependent Staphylococcus aureus small-colony variants are associated
      with extensive alterations in regulator and virulence gene expression profiles.
AB  - Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF
      patients are infected persistently by Staphylococcus aureus. Thymidine-dependent
      trimethoprim-sulfamethoxazole (SXT)-resistant S. aureus small-colony variants
      (SCVs), often in combination with isogenic normal S. aureus phenotypes, are
      highly prevalent and persistent in airway secretions of CF patients due to long
      term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E.
      Harms, R. A. Proctor, and G. Peters, J. Infect. Dis. 177:1023-1029, 1998). In
      this report, SCVs were compared to normal S. aureus by transcription analysis of
      important regulator (sigB, sarA, and agr) and virulence (alpha-hemolysin, hla,
      and protein A, spa) genes. Growth curve analyses revealed longer doubling times
      and lower final densities for SCVs than for normal strains. sigB activity was
      measured by transcription analysis of the sigB target gene asp23. For nearly all
      SCVs, expression of all regulators was decreased as assessed by asp23 reverse
      transcription-PCR for sigB and Northern analysis for sarA and agr. These results
      are in agreement with diminished hla signals in all SCVs and increased spa
      signals in 5 of 10 SCVs compared to the isogenic normal S. aureus. Both
      supplementation of SCVs with thymidine and activation of the agr quorum-sensing
      system by the supernatant of the isogenic normal strain reversed transcription to
      almost normal levels. In conclusion, multiple changes in growth characteristics
      and in regulator and virulence gene expression render SCVs less virulent and
      allow them to survive in the hostile environment present in the airways of CF
      patients, thereby illustrating adaptation of the bacteria during long-term
      persistence.

PMID- 15972502
TI  - Regulation of a type III and a putative secretion system in Edwardsiella tarda by
      EsrC is under the control of a two-component system, EsrA-EsrB.
AB  - Edwardsiella tarda is a gram-negative enteric pathogen that causes hemorrhagic
      septicemia in fish and gastro- and extraintestinal infections in humans. A type
      III secretion system (TTSS) and a putative secretion system (EVP) have been found
      to play important roles in E. tarda pathogenesis. Our previous studies suggested
      that the TTSS and EVP gene clusters were regulated by a two-component system of
      EsrA-EsrB. In the present study, we characterized another regulator, EsrC, which
      showed significant sequence similarity to the AraC family of transcriptional
      regulators. Mutants with in-frame deletions of esrC increased the 50% lethal
      doses in blue gourami fish, reduced extracellular protein production, and failed
      to aggregate. Complementation of esrC restored these three phenotypes. Two
      dimensional gel electrophoresis showed that EsrC regulated the expression of
      secreted proteins encoded by the TTSS (such as EseB and EseD) and EVP (EvpC) gene
      clusters. The expression of esrC required a functional two-component system of
      EsrA-EsrB. EsrC in turn regulated the expression of selected genes encoded in
      TTSS (such as the transcriptional unit of orf29and orf30, but not esaC) and genes
      encoded in the EVP gene cluster. The present study sheds light on the regulation
      of these two key virulence-associated secretion systems and provides greater
      insight into the pathogenic mechanisms of this bacterium.

PMID- 15972503
TI  - Inactivation of the pst system reduces the virulence of an avian pathogenic
      Escherichia coli O78 strain.
AB  - Escherichia coli O78 strains are frequently associated with extraintestinal
      diseases, such as airsacculitis and septicemia, in poultry, livestock, and
      humans. To understand the influence of the pst operon in the virulence of E.
      coli, we introduced mutations into the pst genes of the avian pathogenic E. coli
      (APEC) O78:K80 strain chi7122 by allelic exchange. The mutation of pst genes led
      to the constitutive expression of the Pho regulon. Furthermore, the virulence of
      APEC strain chi7122 in a chicken infection model was attenuated by inactivation
      of the Pst system. The pst mutant caused significantly fewer extraintestinal
      lesions in infected chickens, and bacterial numbers isolated from different
      tissues after infection were significantly lower for the mutant than for the wild
      type strain. Moreover, resistance to the bactericidal effects of rabbit serum and
      acid shock was impaired in the pst mutant, in contrast to the wild-type strain.
      In addition, the MIC of polymyxin was twofold lower for the mutant than for the
      wild-type strain. Although the pst mutant demonstrated an increased
      susceptibility to rabbit serum, this strain was not killed by chicken serum,
      suggesting the presence of differences in host innate immune defenses and
      complement-mediated killing. In APEC O78 strain chi7122, a functional Pst system
      is required for full virulence and resistance to acid shock and polymyxin. Our
      results suggest that the mutation of pst genes induces a deregulation of
      phosphate sensing and changes in the cell surface composition that lead to
      decreased virulence, indicating the importance of the Pst system for the
      virulence of pathogenic E. coli strains from different hosts.

PMID- 15972504
TI  - Microarray analysis of quorum-sensing-regulated genes in Porphyromonas
      gingivalis.
AB  - Quorum sensing is a phenomenon defined as gene regulation in response to cell
      density that regulates various functions in bacteria. The periodontopathogen
      Porphyromonas gingivalis possesses a luxS gene homologue that may encode a quorum
      sensing system. In order to identify genes of P. gingivalis that are regulated by
      luxS, gene expression analysis was done using microarrays and RNA samples from
      the W83 wild-type strain and an isogenic luxS mutant, LY2001. The results
      indicated that 17 open reading frames (ORFs) in LY2001 are upregulated and two
      are downregulated. Real-time PCR was done to confirm the microarray results.
      Among the upregulated ORFs is a group of stress-related genes, including htrA,
      clpB, groEL, dnaK, and the F subunit of alkyl hydroperoxide reductase. This
      suggested that luxS is involved in stress gene regulation in P. gingivalis.
      Stress response experiments, including high-temperature survival, resistance to
      hydrogen peroxide (H2O2), and survival during exposure to low and high pH, were
      performed on the P. gingivalis wild-type and LY2001 strains. LY2001 had a
      significantly higher survival rate than did W83 when stressed at 50 degrees C. No
      difference was found at pH 5, but LY2001 had increased survival compared to W83
      at pH 9. LY2001 also survived better than W83 when stressed with 0.35 mM H2O2.
      These results suggest that luxS might be involved in promoting survival of P.
      gingivalis in the host by regulating its response to host-induced stresses such
      as temperature, H2O2, and pH.

PMID- 15972505
TI  - Trichomonas vaginalis-induced epithelial monolayer disruption and human
      immunodeficiency virus type 1 (HIV-1) replication: implications for the sexual
      transmission of HIV-1.
AB  - The objective of this study was to evaluate potential mechanisms of Trichomonas
      vaginalis involvement in human immunodeficiency virus type 1 (HIV-1)
      transmission. Polarized monolayer integrity of primary cervical and prostate
      epithelial cells or cell lines cultured with T. vaginalis was measured by
      monitoring transepithelium resistance. The effect of T. vaginalis isolates on HIV
      1 passage through polarized epithelial cell monolayers was evaluated for HIV-1
      p24gag in the basolateral supernatants. Coincubation with T. vaginalis isolates
      induced disruption of monolayer integrity and resulted in passage of virus to the
      basolateral side of the monolayer. Furthermore, there was isolate variability in
      which two isolates induced greater monolayer damage and increased HIV-1 passage
      than did the other two isolates. Coincubation of T. vaginalis isolates with
      acutely HIV-1-infected peripheral blood mononuclear cells enhanced HIV-1
      replication. This enhancement was associated with cellular proliferation and
      activation, as well as with tumor necrosis factor alpha production. In contrast
      to the monolayer disruption, the effect of T. vaginalis on HIV-1 replication was
      not isolate dependent. Thus, two mechanisms have been identified that could
      contribute to the epidemiologic association of trichomoniasis with the sexual
      transmission of HIV-1. (i) T. vaginalis disruption of urogenital epithelial
      monolayers could facilitate passage of HIV-1 to underlying layers. (ii)
      Activation of local immune cells by T. vaginalis in the presence of infectious
      HIV-1 might lead to increased viral replication. Collectively, these data suggest
      the need for more vigilant efforts in the diagnosis and treatment of T. vaginalis
      in women and men, especially in countries with a high prevalence of HIV-1.

PMID- 15972506
TI  - Superoxide production in Galleria mellonella hemocytes: identification of
      proteins homologous to the NADPH oxidase complex of human neutrophils.
AB  - The insect immune response has a number of structural and functional similarities
      to the innate immune response of mammals. The objective of the work presented
      here was to establish the mechanism by which insect hemocytes produce superoxide
      and to ascertain whether the proteins involved in superoxide production are
      similar to those involved in the NADPH oxidase-induced superoxide production in
      human neutrophils. Hemocytes of the greater wax moth (Galleria mellonella) were
      shown to be capable of phagocytosing bacterial and fungal cells. The kinetics of
      phagocytosis and microbial killing were similar in the insect hemocytes and human
      neutrophils. Superoxide production and microbial killing by both cell types were
      inhibited in the presence of the NADPH oxidase inhibitor diphenyleneiodonium
      chloride. Immunoblotting of G. mellonella hemocytes with antibodies raised
      against human neutrophil phox proteins revealed the presence of proteins
      homologous to gp91phox, p67phox, p47phox, and the GTP-binding protein rac 2. A
      protein equivalent to p40phox was not detected in insect hemocytes.
      Immunofluorescence analysis localized insect 47-kDa and 67-kDa proteins
      throughout the cytosol and in the perinuclear region. Hemocyte 67-kDa and 47-kDa
      proteins were immunoprecipitated and analyzed by matrix-assisted laser desorption
      ionization--time of flight analysis. The results revealed that the hemocyte 67
      kDa and 47-kDa proteins contained peptides matching those of p67phox and p47phox
      of human neutrophils. The results presented here indicate that insect hemocytes
      phagocytose and kill bacterial and fungal cells by a mechanism similar to the
      mechanism used by human neutrophils via the production of superoxide. We
      identified proteins homologous to a number of proteins essential for superoxide
      production in human neutrophils and demonstrated that significant regions of the
      67-kDa and 47-kDa insect proteins are identical to regions of the p67phox and
      p47phox proteins of neutrophils.

PMID- 15972507
TI  - Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion
      molecule 1 (CD66a)-expressing human B cells and inhibits antibody production.
AB  - Neisseria gonorrhoeae cells (gonococci [GC]), the etiological agents for
      gonorrhea, can cause repeated infections. During and after gonococcal infection,
      local and systemic antigonococcal antibody levels are low. These clinical data
      indicate the possibility that GC may suppress immune responses during infection.
      Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 or CD66a),
      a receptor for GC opacity (Opa) proteins, was shown to mediate inhibitory
      signals. In the present study, human B cells were activated by interleukin-2 to
      express CEACAM1 and then stimulated to secrete antibodies and simultaneously
      coincubated with Opa- and OpaI GC of strain MS11. Our results show that this OpaI
      GC has the ability to inhibit antibody production. The interaction of GC and
      CEACAM1 with human peripheral B cells also results in induction of cell death.
      The same findings were observed in DT40 B cells. This CEACAM1-promoted cell death
      pathway does not involve the inhibitory signals or the tyrosine phosphatases SHP
      1 and SHP-2 but depends on Bruton's tyrosine kinase in DT40 cells. Our results
      suggest that Neisseria gonorrhoeae possesses the ability to suppress antibody
      production by killing CEACAM1-expressing B cells.

PMID- 15972508
TI  - Impact of Helicobacter pylori virulence factors and compounds on activation and
      maturation of human dendritic cells.
AB  - Recently, we and others have shown that Helicobacter pylori induces dendritic
      cell (DC) activation and maturation. However, the impact of virulence factors on
      the interplay between DCs and H. pylori remains elusive. Therefore, we
      investigated the contribution of cag pathogenicity island (PAI) and VacA status
      on cytokine release and up-regulation of costimulatory molecules in H. pylori
      treated DCs. In addition, to characterize the stimulatory capacity of H. pylori
      compounds in more detail, we studied the effect of formalin-inactivated and
      sonicated H. pylori, as well as secreted H. pylori molecules, on DCs. Incubation
      of DCs with viable or formalin-inactivated H. pylori induced comparable secretion
      of interleukin-6 (IL-6), IL-8, IL-10, IL-12, IL-1beta, and tumor necrosis factor
      (TNF). In contrast, IL-12 and IL-1beta release was significantly reduced in DCs
      treated with sonicated bacteria and secreted bacterial molecules. Treatment of
      sonicated H. pylori preparations with polymyxin B resulted in a significant
      reduction of IL-8 and IL-6 secretion, suggesting that H. pylori-derived
      lipopolysaccharide at least partially contributes to activation of immature DCs.
      In addition, the capacity of H. pylori-pulsed DCs to activate allogeneic T cells
      was not affected by cag PAI and VacA. Pretreatment of DC with cytochalasin D
      significantly inhibited secretion of IL-12, IL-1beta, and TNF, indicating that
      phagocytosis of H. pylori contributes to maximal activation of DCs. Taken
      together, our results suggest that DC activation and maturation, as well as DC
      mediated T-cell activation, are independent of the cag PAI and VacA status of H.
      pylori.

PMID- 15972509
TI  - Differential regulation of beta-chemokines in children with Plasmodium falciparum
      malaria.
AB  - Chemokines regulate the host immune response to a variety of infectious
      pathogens. Since the role of chemokines in regulating host immunity in children
      with Plasmodium falciparum malaria has not previously been reported, circulating
      levels of beta-chemokines (MIP-1alpha, MIP-1beta, and RANTES) and their
      respective transcriptional profiles in ex vivo peripheral blood mononuclear cells
      (PBMCs) were investigated. Peripheral blood MIP-1alpha and MIP-1beta levels were
      significantly elevated in mild and severe malaria, while RANTES levels decreased
      with increasing disease severity. Beta-chemokine gene expression profiles in
      blood mononuclear cells closely matched those of circulating beta-chemokines,
      illustrating that PBMCs are a primary source for the observed pattern of beta
      chemokine production during acute malaria. Statistical modeling revealed that
      none of the chemokines was significantly associated with either parasitemia or
      anemia. Additional investigations in healthy children with a known history of
      malaria showed that children with prior severe malaria had significantly lower
      baseline RANTES production than children with a history of mild malaria,
      suggesting inherent differences in the ability to produce RANTES in these two
      groups. Baseline MIP-1alpha and MIP-1beta did not significantly differ between
      children with prior severe malaria and those with mild malaria. Additional in
      vitro experiments in PBMCs from healthy, malaria-naive donors revealed that P.
      falciparum-derived hemozoin (Hz; malarial pigment) and synthetic Hz (beta
      hematin) promote a similar pattern of beta-chemokine gene expression. Taken
      together, the results presented here demonstrate that children with severe
      malaria have a distinct profile of beta-chemokines characterized by increased
      circulating levels of MIP-1alpha and MIP-1beta and decreased RANTES. Altered
      patterns of circulating beta-chemokines result, at least in part, from Hz-induced
      changes in beta-chemokine gene expression in blood mononuclear cells.

PMID- 15972510
TI  - Protective properties of rifampin-resistant rough mutants of Brucella melitensis.
AB  - Vaccination against Brucella infections in animals is usually performed by
      administration of live attenuated smooth B. abortus strain S19 and B. melitensis
      strain Rev1. They are proven effective vaccines against B. abortus in cattle and
      against B. melitensis and B. ovis in sheep and goats, respectively. However, both
      vaccines have the main drawback of inducing O-polysaccharide-specific antibodies
      that interfere with serologic diagnosis of disease. In addition, they retain
      residual virulence, being a cause of abortion in pregnant animals and infection
      in humans. To overcome these problems, one approach is to develop defined rough
      mutant Brucella strains lacking O antigen of lipopolysaccharide. B. abortus rough
      strain RB51, a rifampin-resistant mutant of virulent strain B. abortus 2308, is
      used as a vaccine against B. abortus infection in cattle in some countries.
      However, RB51 is not effective in sheep, and there is only preliminary evidence
      that it is effective in goats. In this study, we tested the efficacies of six
      rifampin-resistant rough strains of B. melitensis in protecting BALB/c mice
      exposed to B. melitensis infection. The protective properties, as well as both
      humoral and cellular immune responses, were assessed in comparison with those
      provided by B. melitensis Rev1 and B. abortus RB51 vaccines. The results
      indicated that these rough mutants were able to induce a very good level of
      protection against B. melitensis infection, similar to that provided by Rev1 and
      superior to that of RB51, without inducing antibodies to O antigen. In addition,
      all B. melitensis mutants were able to stimulate good production of gamma
      interferon. The characteristics of these strains encourage further evaluation of
      them as alternative vaccines to Rev1 in primary host species.

PMID- 15972511
TI  - Identification, cloning, and expression of the CAMP-like factor autotransporter
      gene (cfa) of Bartonella henselae.
AB  - The CAMP reaction was first described by Christie et al. (R. Christie, N. E.
      Atkins, and E. Munch-Petersen, Aust. J. Exp. Biol. 22:197-200, 1944) as the
      synergistic lysis of sheep red blood cells by Staphylococcus aureus
      sphingomyelinase and CAMP factor (cohemolysin), a secreted protein from group B
      streptococci. We observed a CAMP-like reaction when Bartonella henselae was grown
      in close proximity to S. aureus on 5% sheep blood agar. This study describes the
      cloning, sequencing, and characterization of a CAMP-like factor autotransporter
      gene (cfa) from B. henselae. A cosmid library of B. henselae ATCC 49793 was
      constructed using SuperCos1 in Escherichia coli XL1-Blue MR. Cosmids were
      screened for the CAMP reaction, and a quantitative cohemolysis microtiter assay
      was developed using purified sphingomyelinase. Cosmid clones with the strongest
      cohemolytic reaction had similar restriction enzyme patterns. A DNA fragment that
      expressed the cohemolysin determinant was subcloned in a 7,200-bp StuI-BamHI
      fragment which contained a 6,024-bp open reading frame. The deduced amino acid
      sequence showed homology to the family of autotransporters. The autotransporters
      are a group of proteins that mediate their own export through the outer membrane.
      They contain an N-terminal passenger region, the alpha-domain, and a C-terminal
      transporter region, the beta-domain. The alpha-domain contained four, nearly
      identical 42-amino-acid repeats and showed homology to the family of RTX (repeat
      in toxin) hemolysins. The concentrated supernatant of the recombinant strain
      expressed a protein with a molecular mass of 180 kDa on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis consistent with the calculated molecular
      weight of the secreted alpha-domain. In conclusion, we have characterized a novel
      secreted cohemolysin autotransporter protein of B. henselae.

PMID- 15972512
TI  - Identification of Mycobacterium avium genes that affect invasion of the
      intestinal epithelium.
AB  - Invasion of intestinal mucosa of the host by Mycobacterium avium is a critical
      step in pathogenesis and likely involves several different bacterial proteins,
      lipids, glycoproteins, and/or glycolipids. Through the screening of an M. avium
      genomic library in Mycobacterium smegmatis, we have identified a number of M.
      avium genes that are associated with increased invasion of mucosal epithelial
      cells. In order to further investigate these genes, we cloned six of them into a
      plasmid downstream of a strong mycobacterial promoter (L5 mycobacterial phage
      promoter), resulting in constitutive expression. Bacteria were then evaluated for
      increased expression and examined for invasion of HT-29 intestinal epithelial
      cells. The genes identified encode proteins that are similar to (i) M.
      tuberculosis coenzyme A carboxylase, (ii) M. tuberculosis membrane proteins of
      unknown function, (iii) M. tuberculosis FadE20, (iv) a Mycobacterium
      paratuberculosis surface protein, and (v) M. tuberculosis cyclopropane fatty acyl
      phopholipid synthase. The constitutive expression of these genes confers to M.
      avium the ability to invade HT-29 intestinal epithelial cells with a severalfold
      increase in efficiency compared to both the wild-type M. avium and M. avium
      containing the vector alone. Using the murine intestinal ligated loop model, it
      was observed that the constitutive expression of M. avium proteins has a modest
      impact on the ability to enter the intestinal mucosa when compared with the wild
      type control, suggesting that under in vivo conditions these genes are expressed
      at higher levels. Evaluation of the expression of these invasion-related genes
      indicated that under conditions similar to the intestinal lumen environment, the
      genes identified are upregulated. These data suggest that invasion of the
      intestinal mucosa is an event that requires the participation of several
      bacterial factors and the expression of the genes that encode them is less
      observed under standard laboratory growth conditions.

PMID- 15972513
TI  - Roles of 3-deoxy-D-manno-2-octulosonic acid transferase from Moraxella
      catarrhalis in lipooligosaccharide biosynthesis and virulence.
AB  - Lipooligosaccharide (LOS), a major outer membrane component of Moraxella
      catarrhalis, is a possible virulence factor in the pathogenesis of human
      infections caused by the organism. However, information about the roles of the
      oligosaccharide chain from LOS in bacterial infection remains limited. Here, a
      kdtA gene encoding 3-deoxy-D-manno-2-octulosonic acid (Kdo) transferase, which is
      responsible for adding Kdo residues to the lipid A portion of the LOS, was
      identified by transposon mutagenesis and construction of an isogenic kdtA mutant
      in strain O35E. The resulting O35EkdtA mutant produced only lipid A without any
      core oligosaccharide, and it was viable. Physicochemical and biological analysis
      revealed that the mutant was susceptible to hydrophobic reagents and a
      hydrophilic glycopeptide and was sensitive to bactericidal activity of normal
      human serum. Importantly, the mutant showed decreased toxicity by the Limulus
      amebocyte lysate assay, reduced adherence to human epithelial cells, and enhanced
      clearance in lungs and nasopharynx in a mouse aerosol challenge model. These data
      suggest that the oligosaccharide moiety of the LOS is important for the
      biological activity of the LOS and the virulence capability of the bacteria in
      vitro and in vivo. This study may bring new insights into novel vaccines or
      therapeutic interventions against M. catarrhalis infections.

PMID- 15972514
TI  - Effects of estradiol on lipopolysaccharide and Pam3Cys stimulation of
      CCL20/macrophage inflammatory protein 3 alpha and tumor necrosis factor alpha
      production by uterine epithelial cells in culture.
AB  - We have previously demonstrated that rat uterine epithelial cells (UEC) produce
      CCL20/macrophage inflammatory protein 3 alpha (MIP3alpha) and tumor necrosis
      factor alpha (TNF-alpha) in response to live and heat-killed Escherichia coli and
      to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and
      Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced
      CCL20/MIP3alpha and TNF-alpha secretion, primary cultures of rat UEC were
      incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated
      for an additional 12 h. E2 inhibited the constitutive secretion of TNF-alpha and
      CCL20/MIP3alpha into culture media. Interestingly, E2 pretreatment enhanced
      CCL20/MIP3alpha secretion due to LPS and Pam3Cys administration. In contrast, and
      at the same time, E2 lowered the TNF-alpha response to both PAMP. To determine
      whether estrogen receptors (ER) mediated the effects of E2, epithelial cells were
      incubated with E2 and/or ICI 182,780, a known ER antagonist. ICI 182,780 had no
      effect on E2 inhibition of constitutive TNF-alpha and CCL20/MIP3alpha secretion.
      In contrast, ICI 182,780 reversed the stimulatory effect of E2 on LPS- and/or
      Pam3Cys-induced CCL20/MIP3alpha secretion as well as partially reversed the
      inhibitory effect of E2 on TNF-alpha production by epithelial cells. Overall,
      these results indicate that E2 regulates the production of TNF-alpha and
      CCL20/MIP3alpha by UEC in the absence as well as presence of PAMP. Since
      CCL20/MIP3alpha has antimicrobial activity and is chemotactic for immune cells,
      these studies suggest that regulation of CCL20/MIP3alpha and TNF-alpha by E2 and
      PAMP may have profound effects on innate and adaptive immune responses to
      microbial challenge in the female reproductive tract.

PMID- 15972515
TI  - Endocrine perturbation increases susceptibility of mice to anthrax lethal toxin.
AB  - Bacillus anthracis lethal toxin (LT) causes vascular collapse and high lethality
      in BALB/cJ mice, intermediate lethality in C57BL/6J mice, and no lethality in
      DBA/2J mice. We found that adrenalectomized (ADX) mice of all three strains had
      increased susceptibility to LT. The increased susceptibility of ADX-DBA/2J mice
      was not accompanied by changes in their macrophage sensitivity or cytokine
      response to LT. DBA/2J mice showed no change in serum corticosteroid levels in
      response to LT injection, while BALB/cJ mice showed a fivefold increase in serum
      corticosterone. However, LT inhibited dexamethasone (DEX)-induced glucocorticoid
      receptor gene activation to similar extents in all three strains. DEX treatment
      did not rescue ADX mice from LT-mediated mortality. Surprisingly, oral DEX
      treatment also sensitized adrenally intact DBA/2J mice to LT lethality at all
      doses tested and also exacerbated LT-mediated pathogenesis and mortality in
      BALB/cJ mice. Aldosterone did not protect ADX mice from toxin challenge. These
      results indicate that susceptibility to anthrax LT in mice depends on a fine but
      easily perturbed balance of endocrine functions. Thus, the potentially
      detrimental consequences of steroid therapy for anthrax must be considered in
      treatment protocols for this disease.

PMID- 15972516
TI  - Innate immune defense against pneumococcal pneumonia requires pulmonary
      complement component C3.
AB  - Complement is known to be involved in protection against systemic infection with
      Streptococcus pneumoniae. However, less is known about effects of complement
      within the lungs during pneumococcal pneumonia. By intranasally infecting
      transgenic mice unable to express complement C3, we investigated the role of
      complement in pulmonary defenses against S. pneumoniae. It was demonstrated that
      within the lungs, there is a requirement for C3 during the initial hours of
      infection. It was found that within 1 h of infection, bacterial loads decreased
      within lung airways of control mice as C3 protein increased. The lack of C3
      resulted in the inability to control growth of wild-type or attenuated
      pneumococci within the lungs and bloodstream, resulting in an overwhelming
      inflammatory response and shorter survival times. Our results show that during
      the initial hours of infection with S. pneumoniae, C3 is protective within the
      lungs and subsequently plays an important role systemically.

PMID- 15972517
TI  - Sequence diversity and antigenic variation at the rag locus of Porphyromonas
      gingivalis.
AB  - The rag locus of Porphyromonas gingivalis W50 encodes RagA, a predicted tonB
      dependent receptor protein, and RagB, a lipoprotein that constitutes an
      immunodominant outer membrane antigen. The low G+C content of the locus, an
      association with mobility elements, and an apparent restricted distribution in
      the species suggested that the locus had arisen by horizontal gene transfer. In
      the present study, we have demonstrated that there are four divergent alleles of
      the rag locus. The original rag allele found in W50 was renamed rag-1, while
      three novel alleles, rag-2 to rag-4, were found in isolates lacking rag-1. The
      three novel alleles encoded variants of RagA with 63 to 71% amino acid identity
      to RagA1 and each other and variants of RagB with 43 to 56% amino acid identity.
      The RagA/B proteins have homology to numerous Bacteroides proteins, including
      SusC/D, implicated in polysaccharide uptake. Monoclonal and polyclonal antibodies
      raised against RagB1 of P. gingivalis W50 did not cross-react with proteins from
      isolates carrying different alleles. In a laboratory collection of 168 isolates,
      26% carried rag-1, 36% carried rag-2, 25% carried rag-3, and 14% carried rag-4
      (including the type strain, ATCC 33277). Restriction profiles of the locus in
      different isolates demonstrated polymorphism within each allele, some of which is
      accounted for by the presence or absence of insertion sequence elements. By
      reference to a previously published study on virulence in a mouse model (M. L.
      Laine and A. J. van Winkelhoff, Oral Microbiol. Immunol. 13:322-325, 1998),
      isolates that caused serious disease in mice were significantly more likely to
      carry rag-1 than other rag alleles.

PMID- 15972518
TI  - Alveolar response to Pseudomonas aeruginosa: role of the type III secretion
      system.
AB  - The type III secretion system (TTSS) is a specialized cytotoxin-translocating
      apparatus of gram-negative bacteria which is involved in lung injury, septic
      shock, and a poor patient outcome. Recent studies have attributed these effects
      mainly to the ExoU effector protein. However, few studies have focused on the
      ExoU-independent pathogenicity of the TTSS. For the present study, we compared
      the pathogenicities of two strains of Pseudomonas aeruginosa in a murine model of
      acute lung injury. We compared the CHA strain, which has a functional TTSS
      producing ExoS and ExoT but not ExoU, to an isogenic mutant with an inactivated
      exsA gene, CHA-D1, which does not express the TTSS at all. Rats challenged with
      CHA had significantly increased lung injury, as assessed by the wet/dry weight
      ratio for the lungs and the protein level in bronchoalveolar lavage fluid (BALF)
      at 12 h, compared to those challenged with CHA-D1. Consistent with these
      findings, the CHA strain was associated with increased in vitro cytotoxicity on
      A549 cells, as assessed by the release of lactate dehydrogenase. CHA was also
      associated at 12 h with a major decrease in polymorphonuclear neutrophils in
      BALF, with a proinflammatory response, as assessed by the amounts of tumor
      necrosis factor alpha and interleukin-1beta, and with decreased bacterial
      clearance from the lungs, ultimately leading to an increased mortality rate.
      These results demonstrate that the TTSS has a major role in P. aeruginosa
      pathogenicity independent of the role of ExoU. This report underscores the
      crucial roles of ExoS and ExoT or other TTSS-related virulence factors in
      addition to ExoU.

PMID- 15972519
TI  - Identification of a novel adhesion molecule involved in the virulence of
      Legionella pneumophila.
AB  - Legionella pneumophila is an intracellular bacterium, and its successful
      parasitism in host cells involves two reciprocal phases: transmission and
      intracellular replication. In this study, we sought genes that are involved in
      virulence by screening a genomic DNA library of an L. pneumophila strain, 80-045,
      with convalescent-phase sera of Legionnaires' disease patients. Three antigens
      that reacted exclusively with the convalescent-phase sera were isolated. One of
      them, which shared homology with an integrin analogue of Saccharomyces
      cerevisiae, was named L. pneumophila adhesion molecule homologous with integrin
      analogue of S. cerevisiae (LaiA). The laiA gene product was involved in L.
      pneumophila adhesion to and invasion of the human lung alveolar epithelial cell
      line A549 during in vitro coculture. However, its presence did not affect
      multiplication of L. pneumophila within a U937 human macrophage cell line.
      Furthermore, after intranasal infection of A/J mice, the laiA mutant was
      eliminated from lungs and caused reduced mortality compared to the wild isolate.
      Thus, we conclude that the laiA gene encodes a virulence factor that is involved
      in transmission of L. pneumophila 80-045 and may play a role in Legionnaires'
      disease in humans.

PMID- 15972520
TI  - The gonococcal Fur-regulated tbpA and tbpB genes are expressed during natural
      mucosal gonococcal infection.
AB  - Iron is limiting in the human host, and bacterial pathogens respond to this
      environment by regulating gene expression through the ferric uptake regulator
      protein (Fur). In vitro studies have demonstrated that Neisseria gonorrhoeae
      controls the expression of several critical genes through an iron- and Fur
      mediated mechanism. While most in vitro experiments are designed to determine the
      response of N. gonorrhoeae to an exogenous iron concentration of zero, these
      organisms are unlikely to be exposed to such severe limitations of iron in vivo.
      To determine if N. gonorrhoeae expresses iron- and Fur-regulated genes in vivo
      during uncomplicated gonococcal infection, we examined gene expression profiles
      of specimens obtained from male subjects with urethral infections. RNA was
      isolated from urethral swab specimens and used as a template to amplify, by
      reverse transcriptase PCR (RT-PCR), gonococcal genes known to be regulated by
      iron and Fur (tbpA, tbpB, and fur). The constitutively expressed gonococcal rmp
      gene was used as a positive control. RT-PCR analysis indicated that gonorrhea
      positive specimens where rmp expression was seen were also 93% (51/55) fbpA
      positive, 87% (48/55) tbpA positive, and 86% (14 of 16 tested) tbpB positive. In
      addition, we detected a fur transcript in 79% (37 of 47 tested) of positive
      specimens. We also measured increases in levels of immunoglobulin G antibody
      against TbpA (91%) and TbpB (73%) antigens in sera from infected male subjects
      compared to those in uninfected controls. A positive trend between tbpA gene
      expression and TbpA antibody levels in sera indicated a relationship between
      levels of gene expression and immune response in male subjects infected with
      gonorrhea for the first time. These results indicate that gonococcal iron- and
      Fur-regulated tbpA and tbpB genes are expressed in gonococcal infection and that
      male subjects with mucosal gonococcal infections exhibit antibodies to these
      proteins.

PMID- 15972521
TI  - Inhibition of chondroitin-4-sulfate-specific adhesion of Plasmodium falciparum
      infected erythrocytes by sulfated polysaccharides.
AB  - Adhesion of Plasmodium falciparum-infected erythrocytes to placental chondroitin
      4-sulfate (CSA) has been linked to the severe disease outcome of pregnancy
      associated malaria. Soluble polysaccharides that release mature-stage parasitized
      erythrocytes into the peripheral circulation may help elucidate these
      interactions and have the potential to aid in developing therapeutic strategies.
      We have screened a panel of 11 sulfated polysaccharides for their capacities to
      inhibit adhesion of infected erythrocytes to CSA expressed on CHO-K1 cells and ex
      vivo human placental tissue. Two carrageenans and a cellulose sulfate (CS10) were
      able to inhibit adhesion to CSA and to cause already bound infected erythrocytes
      to de-adhere in a dose-dependent manner. CS10, like CSA and in contrast to all
      other compounds tested, remained bound to infected erythrocytes after washing and
      continued to inhibit binding. Both carrageenans and CS10 inhibited adhesion to
      placental tissue. Although highly sulfated dextran sulfate can inhibit CSA
      mediated adhesion to CHO cells, this polysaccharide amplified adhesion to
      placental tissue severalfold, demonstrating the importance of evaluating
      inhibitory compounds in systems as close to in vivo as possible. Interestingly,
      and in contrast to all other compounds tested, which had a random distribution of
      sulfate groups, CS10 exhibited a clustered sulfate pattern along the polymer
      chain, similar to that of the undersulfated placental CSA preferred by placental
      tissue-binding infected erythrocytes. Therefore, the specific anti-adhesive
      capacity observed here seems to depend not only on the degree of charge and
      sulfation but also on a particular pattern of sulfation.

PMID- 15972522
TI  - Production of nontypeable Haemophilus influenzae HtrA by recombinant Bordetella
      pertussis with the use of filamentous hemagglutinin as a carrier.
AB  - Bordetella pertussis, the etiologic agent of whooping cough, is a highly
      infectious human pathogen capable of inducing mucosal and systemic immune
      responses upon a single intranasal administration. In an attenuated, pertussis
      toxin (PTX)-deficient recombinant form, it may therefore constitute an efficient
      bacterial vector that is particularly well adapted for the delivery of
      heterologous antigens to the respiratory mucosa. Filamentous hemagglutinin (FHA)
      has been used as a carrier to present foreign antigens at the bacterial surface,
      thereby inducing local, systemic, and protective immune responses to these
      antigens in mice. Both full-length and truncated (Fha44) forms of FHA have been
      used for antigen presentation. To investigate the effect of the carrier (FHA or
      Fha44) on antibody responses to passenger antigens, we genetically fused the HtrA
      protein of nontypeable Haemophilus influenzae to either FHA form. The fha-htrA
      and Fha44 gene-htrA hybrids were expressed as single copies inserted into the
      chromosome of PTX-deficient B. pertussis. Both chimeras were secreted into the
      culture supernatants of the recombinant strains and were recognized by anti-FHA
      and anti-HtrA antibodies. Intranasal infection with the strain producing the FHA
      HtrA hybrid led to significantly higher anti-HtrA and anti-FHA antibody titers
      than those obtained in mice infected with the Fha44-HtrA-producing strain.
      Interestingly, the B. pertussis strain producing the Fha44-HtrA chimera colonized
      the mouse lungs more efficiently than the parental, Fha44-producing strain and
      gave rise to higher anti-FHA antibody titers than those induced by the parental
      strain.

PMID- 15972523
TI  - Virulence attenuation and live vaccine potential of aroA, crp cdt cya, and
      plasmid-cured mutants of Salmonella enterica serovar Abortusovis in mice and
      sheep.
AB  - Three live vaccine candidates of Salmonella enterica subspecies I serotype
      Abortusovis (aroA, cya crp cdt, and plasmid-cured strains) have been developed,
      and their efficacies in inducing humoral antibodies and protecting against
      abortion after challenge with wild-type strain SS44 were evaluated in sheep.
      Following estrus synchronization, animals were immunized 3 weeks after
      fertilization and boosted once 3 weeks later. Following challenge with wild-type
      SS44, pregnancy failure of vaccinated ewes was reduced compared to that of
      nonimmunized controls. Attenuation of each vaccine was also assessed in challenge
      experiments with nonimmunized pregnant ewes and in BALB/c mice. All three vaccine
      candidates appear to be safe for use in sheep and provide a model for the
      development of live vaccine candidates against naturally occurring ovine
      salmonellosis.

PMID- 15972524
TI  - Bovine intestinal alkaline phosphatase attenuates the inflammatory response in
      secondary peritonitis in mice.
AB  - Lipopolysaccharide (LPS) contributes importantly to morbidity and mortality in
      sepsis. Bovine intestinal alkaline phosphatase (BIAP) was demonstrated to
      detoxify LPS through dephosphorylation. LPS injection combined with BIAP reduced
      inflammation and improved survival in various experimental settings. In this
      study, single-dose intravenous administration of BIAP (0.15 IU/g) was applied in
      a murine cecal ligation and puncture (CLP) model of polymicrobial sepsis. Saline
      was given as control (S group). Treatment with BIAP prior to CLP (prophylaxis;
      BIAP-P group) or shortly after (early treatment; BIAP-ET group) reduced cytokine
      concentrations in plasma and peritoneal lavage fluid (PLF). Tumor necrosis factor
      alpha peak levels decreased from 170 pg/ml (S) to 57.5 (BIAP-P) and 82.5 (BIAP
      ET) in plasma and in PLF from 57.5 pg/ml (S) to 35.3 (BIAP-P) and 16.8 (BIAP-ET)
      (all, P < 0.05). Peak interleukin-6 levels in plasma decreased from 19.3 ng/ml
      (S) to 3.4 (BIAP-P) and 11.5 (BIAP-ET) and in PLF from 32.6 ng/ml (S) to 13.4
      (BIAP-P) and 10.9 (BIAP-ET) (all, P < 0.05). Macrophage chemoattractant protein 1
      peak levels in plasma decreased from 2.0 ng/ml (S) to 1.0 (BIAP-P) and 0.7 (BIAP
      ET) and in PLF from 6.4 (S) to 2.3 (BIAP-P) and 1.3 ng/ml (BIAP-ET) (all, P <
      0.05). BIAP-treated groups showed decreased transaminase activity in plasma and
      decreased myeloperoxidase activity in the lung, indicating reduced associated
      hepatocellular and pulmonary damage. Survival was not significantly altered by
      BIAP in this single-dose regimen. In polymicrobial secondary peritonitis, both
      prophylactic and early BIAP treatment attenuates the inflammatory response both
      locally and systemically and reduces associated liver and lung damage.

PMID- 15972525
TI  - Chlamydia pneumoniae augments the oxidized low-density lipoprotein-induced death
      of mouse macrophages by a caspase-independent pathway.
AB  - Chlamydia pneumoniae is a common respiratory pathogen that is associated with an
      increased risk of cardiovascular disease. However, the mechanisms by which C.
      pneumoniae contributes to cardiovascular disease have not been determined yet. C.
      pneumoniae infection may accelerate the death of cells within atherosclerotic
      lesions and contribute to the formation of unstable lesions. To test this
      hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded
      mouse macrophages was investigated. It was observed that RAW 264.7 cells are
      highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL)
      and exhibit markers of cell death within 24 h of treatment with as little as 5
      microg/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or
      heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection
      for 24 to 72 h stimulated both additional binding of annexin V and the uptake of
      propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on
      cell death independent of a sustained infection. However, unlike oxidized LDL, C.
      pneumoniae infection does not activate caspase 3 or induce formation of the
      mitochondrial transition pore or the fragmentation of DNA, all of which are
      classical markers of apoptosis. Furthermore, primary bone marrow macrophages
      isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are
      resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae
      kills cells by a caspase-independent pathway and that the process is potentially
      mediated by activation of TLR-2.

PMID- 15972526
TI  - Effect of Chlamydia pneumoniae on cellular ATP content in mouse macrophages: role
      of Toll-like receptor 2.
AB  - Chlamydiae are obligate intracellular gram-negative bacteria and are dependent on
      the host cell for ATP. Thus, chlamydial infection may alter the intracellular
      levels of ATP and affect all energy-dependent processes within the cell. We have
      shown that both live C. pneumoniae and inactivated C. pneumoniae induce markers
      of cell death prior to completion of the bacterial growth cycle. As depletion of
      ATP could account for the observed increase in cell death, the effects of C.
      pneumoniae on ATP concentrations within mouse macrophages were investigated.
      Live, heat-killed, and UV-inactivated C. pneumoniae cultures (at multiplicities
      of infection [MOIs] of 0.01, 0.1, and 1.0) were incubated with mouse bone marrow
      macrophages isolated from C57BL/6J mice and mice deficient in Toll-like
      receptors. Treatment of the macrophages with both live and inactivated C.
      pneumoniae increased the ATP content of the cells. In cells infected with live C.
      pneumoniae, the increase was inversely proportional to the MOI. In cells treated
      with inactivated C. pneumoniae, the increase in ATP content was smaller than that
      induced by infection with live organisms and was proportional to the MOI. The
      increase in ATP content early in the developmental cycle was independent of the
      growth of C. pneumoniae, while sustained induction required live organisms. The
      capacity of C. pneumoniae to increase the ATP content was ablated in macrophages
      deficient in expression of either Toll-like receptor 2 or the Toll-like receptor
      accessory protein MyD88. In contrast, no effect was observed in macrophages
      lacking expression of Toll-like receptor 4.

PMID- 15972527
TI  - SepZ/EspZ is secreted and translocated into HeLa cells by the enteropathogenic
      Escherichia coli type III secretion system.
AB  - Enteropathogenic Escherichia coli (EPEC) is a major bacterial cause of infantile
      diarrhea in developing countries and is the prototype for a group of
      gastrointestinal pathogens causing characteristic attaching and effacing (A/E)
      histopathology on intestinal epithelia. A/E pathogens utilize a type III
      secretion system (TTSS), encoded by the locus of enterocyte effacement (LEE)
      pathogenicity island, to deliver effector proteins into host cells. Here, we
      investigate sequence divergence of the LEE-encoded SepZ protein and identify it
      as a TTSS-secreted and -translocated molecule. SepZ is hypervariable among A/E
      pathogens, with sequences sharing between 60 to 81% amino acid identity with SepZ
      of EPEC. A SepZ-CyaA fusion was secreted and translocated into HeLa cells in a
      TTSS-dependent manner. Additionally, we determined that the first 20 amino acids
      of SepZ were sufficient to direct its translocation. In contrast to previous
      studies suggesting a role in invasion and the structure and/or regulation of the
      TTSS, we found that SepZ does not mediate uptake of EPEC into host cells or
      affect translocation and tyrosine phosphorylation of the translocated intimin
      receptor. Immunohistochemistry reveals that, after an extended HeLa cell
      infection, accumulated SepZ can be detected beneath the site of bacterial
      attachment in a subset of pedestal regions. To indicate its newly identified
      status as a translocated effector protein, we propose to rename SepZ as EspZ.

PMID- 15972528
TI  - sciS, an icmF homolog in Salmonella enterica serovar Typhimurium, limits
      intracellular replication and decreases virulence.
AB  - Salmonella enterica serovar Typhimurium utilizes macrophages to disseminate from
      the intestine to deeper tissues within the body. While S. enterica serovar
      Typhimurium has been shown to kill its host macrophage, it can persist
      intracellularly beyond 18 h postinfection. To identify factors involved in late
      stages of infection, we screened a transposon library made in S. enterica serovar
      Typhimurium for the ability to persist in J774 macrophages at 24 h postinfection.
      Through this screen, we identified a gene, sciS, found to be homologous to icmF
      in Legionella pneumophila. icmF, which is required for intracellular
      multiplication, is conserved in several gram-negative pathogens, and its homolog
      appears to have been acquired horizontally in S. enterica serovar Typhimurium. We
      found that an sciS mutant displayed increased intracellular numbers in J774
      macrophages when compared to the wild-type strain at 24 h postinfection. sciS was
      maximally transcribed at 27 h postinfection and is repressed by SsrB, an
      activator of genes required for promoting intracellular survival. Finally, we
      demonstrate that an sciS mutant is hypervirulent in mice when administered
      intragastrically. Taken together, these data indicate a role for SciS in
      controlling intracellular bacterial levels at later stages of infection and
      attenuating virulence in a murine host.

PMID- 15972529
TI  - Effects of a probiotic strain of Enterococcus faecium on the rate of natural
      chlamydia infection in swine.
AB  - Chlamydiae are obligately intracellular pathogens which cause infections
      associated with a broad range of diseases in both livestock and humans. In
      addition, a large proportion of animals may become persistently infected
      asymptomatic carriers and serve as reservoirs for other animals which also shed
      these potential zoonotic pathogens. Reducing the chlamydial load of animals is
      therefore of major importance, and since large-scale antibiotic treatment is
      neither desired nor feasible, alternative means of prevention are needed. Here we
      performed a study comparing the efficacy of a probiotic strain of Enterococcus
      faecium on the reduction of both the rate of natural infection and the shedding
      of chlamydiae in swine. The presence of Chlamydiaceae was detected by species
      specific PCR of fecal samples of sows taken at three times prior to the birth of
      piglets. Piglets delivered from chlamydia-positive sows in either the control or
      the probiotic group were also examined for the frequency of chlamydiae at various
      ages. Eighty-five percent of the piglets from the control group were found to be
      chlamydia positive, whereas chlamydiae were found in only 60% of piglets from the
      probiotic group, results confirmed by fluorescence in situ hybridization and
      immunohistology, which showed higher rates of infection in the control group. In
      addition to the reduced frequency of chlamydia-positive piglets in the probiotic
      group, the time of appearance of positive samples was delayed. To our knowledge,
      these data show for the first time that a probiotic strain of E. faecium can
      reduce the rate of carryover infections of piglets by obligate intracellular
      pathogens.

PMID- 15972530
TI  - SlyA regulates function of Salmonella pathogenicity island 2 (SPI-2) and
      expression of SPI-2-associated genes.
AB  - During the systemic phase of murine infection with Salmonella enterica serovar
      Typhimurium, bacterial virulence is correlated with the ability to grow and
      survive within host macrophages. Salmonella pathogenicity island 2 (SPI-2),
      encoding a type three secretion system, has emerged as an important contributor
      to Salmonella intracellular growth. SPI-2 mutants have been proposed to be more
      accessible than wild-type Salmonella to oxyradicals generated by the NADPH
      phagocyte oxidase. We performed mixed infections of mice to investigate the
      relationship between SPI-2 and SlyA, a transcriptional regulator that confers
      resistance to oxyradicals. In mixed-infection experiments, the SPI-2 null mutant
      was severely attenuated in virulence, whereas slyA mutants were only mildly
      attenuated. Surprisingly, further experiments indicated that the function of SPI
      2 was partially dependent on slyA. The intracellular behavior of a slyA mutant in
      infected cells was consistent with inefficient SPI-2 expression, as formation of
      Salmonella-induced filaments and the intracellular F-actin meshwork, features
      that depend on SPI-2, were present at abnormally low frequencies. Furthermore,
      the translocated levels of the SPI-2 effector SseJ were severely reduced in a
      strain carrying a mutation in slyA. We used flow cytometry to investigate the
      role of SlyA in expression of green fluorescent protein (GFP) from
      transcriptional fusions with promoters of either of two other SPI-2 effector
      genes, sifB and sifA. The slyA mutant exhibited reduced GFP expression from both
      promoters. Combining mutations in slyA and other regulators of SPI-2 indicated
      that SlyA acts through the SsrAB two-component regulatory system. SlyA exhibits
      partial functional redundancy with OmpR-EnvZ and contributes to the
      transcriptional response to low osmolarity and the absence of calcium, two
      environmental stimuli that promote SPI-2 gene expression.

PMID- 15972531
TI  - Quantitative dynamics of Plasmodium yoelii sporozoite transmission by infected
      anopheline mosquitoes.
AB  - Malaria transmission begins with the injection of Plasmodium sporozoites into the
      skin of a vertebrate host by infected anopheline mosquitoes. Although the size of
      the sporozoite inoculum likely affects the course of the disease, the number of
      sporozoites injected by infected mosquitoes has not been determined in vivo.
      Using a quantitative PCR assay, we determined the number of sporozoites injected
      into mice by single mosquitoes. Analysis of 59 mosquito feedings showed that a
      single infected mosquito injected between 0 and 1,297 sporozoites, with a mean of
      123 and a median of 18. Twenty-two percent of infected mosquitoes injected no
      sporozoites. The number of sporozoites injected was only weakly correlated to the
      salivary gland load. To better understand the large variability in sporozoite
      injection among mosquitoes, we quantified the sporozoites injected by individual
      mosquitoes on three different days. Approximately 20% of moderately to heavily
      infected mosquitoes injected few to no sporozoites on all 3 days, suggesting that
      some mosquitoes are poor transmitters of sporozoites. Other mosquitoes injected
      high numbers of sporozoites on at least one of the days observed and minimal
      numbers on the other day(s), supporting the hypothesis that sporozoite injection
      is discontinuous, a pattern that may aid in the establishment of malaria
      infection.

PMID- 15972532
TI  - LidA, a translocated substrate of the Legionella pneumophila type IV secretion
      system, interferes with the early secretory pathway.
AB  - Legionella pneumophila uses a type IV secretion system to deliver effector
      molecules into the host cell and establish its replication vacuole. In this
      study, we investigated the role of LidA, a translocated substrate associated with
      the surface of the L. pneumophila-containing vacuole. LidA is secreted into the
      host cell throughout the replication cycle of the bacteria and associates with
      compartments of the early secretory pathway. When overexpressed in mammalian
      cells or yeast, LidA interferes with the early secretory pathway, probably via a
      domain predicted to be rich in coiled-coil structure. Finally, during
      intracellular replication, the replication vacuoles are in close contact with the
      endoplasmic reticulum-Golgi intermediate compartment and the Golgi apparatus,
      suggesting a positive correlation between intracellular growth and association of
      the vacuole with compartments of the early secretory pathway. We propose that
      LidA is involved in the recruitment of early secretory vesicles to the L.
      pneumophila-containing vacuole and that the vacuole associates with the secretory
      pathway to facilitate this process.

PMID- 15972533
TI  - Profile of gene expression in a murine model of allergic bronchopulmonary
      aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) results from the interactions of
      the Aspergillus allergens and immune system of the patients. We studied the gene
      expression profile in a mouse model of ABPA. Of the 12,000 genes studied, 1,300
      genes showed enhanced expression and represent chemokine, cytokine, growth
      factor, signal transduction, and transmembrane receptor genes as well as genes
      related to arginine metabolism.

PMID- 15972534
TI  - Enteropathogenic Escherichia coli type III effectors EspG and EspG2 disrupt the
      microtubule network of intestinal epithelial cells.
AB  - Enteropathogenic Escherichia coli infection of intestinal epithelial cells leads
      to localized depletion of the microtubule cytoskeleton, an effect that is
      dependent on delivery of type III translocated effector proteins EspG and Orf3
      (designated EspG2) to the site of depletion. Microtubule depletion involved
      disruption rather than displacement of microtubules.

PMID- 15972535
TI  - Role of the distal sarA promoters in SarA expression in Staphylococcus aureus.
AB  - The global regulatory locus sarA comprises a 375-bp open reading frame that is
      driven by three promoters, the proximal P1 and distal P3 and P2 promoters. We
      mutated the weaker P3 and P2 promoters to ascertain the effect of the change on
      SarA protein and target gene expression. Our results indicated that the solely
      active P1 promoter led to a lower SarA protein level, which has an effect on agr
      transcription and subsequently had corresponding effects on hla, sspA, and spa
      transcription, probably in both agr-independent and agr-dependent manners.

PMID- 15972536
TI  - Role of motility and flagellin glycosylation in the pathogenesis of Pseudomonas
      aeruginosa burn wound infections.
AB  - In this study, we tested the contribution of flagellar motility, flagellin
      structure, and its glycosylation in Pseudomonas aeruginosa using genetically
      defined flagellar mutants. All mutants and their parent strains were tested in a
      burned-mouse model of infection. Motility and glycosylation of the flagellum
      appear to be important determinants of flagellar-mediated virulence in this
      model. This is the first report where genetically defined flagellar variants of
      P. aeruginosa were tested in the burned-mouse model of infection.

PMID- 15972537
TI  - KatA, the major catalase, is critical for osmoprotection and virulence in
      Pseudomonas aeruginosa PA14.
AB  - We demonstrate that among the three monofunctional catalases of Pseudomonas
      aeruginosa PA14, KatA and, to a lesser extent, KatB, but not KatE, are required
      for resistance to peroxide and osmotic stresses. KatA is crucial for adaptation
      to H2O2 stress and full virulence in both Drosophila melanogaster and mice. This
      dismantling of catalase roles represents a specialized catalytic system primarily
      involving KatA in responses to adverse environmental conditions.

PMID- 15972538
TI  - Adherence to and invasion of human brain microvascular endothelial cells are
      promoted by fibrinogen-binding protein FbsA of Streptococcus agalactiae.
AB  - Streptococcus agalactiae is a frequent cause of bacterial sepsis and meningitis
      in neonates. During the course of infection, S. agalactiae colonizes and invades
      a number of host compartments, thereby interacting with different host tissues.
      Deletion of the fbsA gene, encoding the fibrinogen protein FbsA, significantly
      impaired the adherence and invasion of human brain microvascular endothelial
      cells (HBMEC) by S. agalactiae. The adherence and invasiveness of an fbsA
      deletion mutant were restored by reintroducing the fbsA gene on an expression
      vector. Heterologous expression of fbsA in Lactococcus lactis enabled this
      bacterium to adhere to but not to invade HBMEC, suggesting that FbsA is a
      streptococcal adhesin. Finally, host cell adherence and invasion were
      significantly blocked in competition experiments with either purified FbsA fusion
      protein or a monoclonal antibody directed against the fibrinogen-binding epitope
      of FbsA. The S. agalactiae fbsA mutant induced a release of the neutrophil
      chemoattractant interleukin-8 (IL-8) equal to that induced by the wild type.
      Taken together, our studies demonstrate that FbsA promotes the adherence of S.
      agalactiae to HBMEC but that FbsA neither mediates the bacterial invasion into
      host cells nor plays a role in IL-8 release for HBMEC.

PMID- 15972539
TI  - Involvement of Listeria monocytogenes phosphatidylinositol-specific phospholipase
      C and host protein kinase C in permeabilization of the macrophage phagosome.
AB  - We have previously shown that phosphatidylinositol-specific phospholipase C (PI
      PLC) produced by Listeria monocytogenes activates a host protein kinase C (PKC)
      cascade which promotes escape of the bacterium from a macrophage-like cell
      phagosome. Here, we provide evidence linking bacterial PI-PLC and host PKC beta
      to phagosome permeabilization, which precedes escape.

PMID- 15972540
TI  - Inhibition of proteolytic activity of a chlamydial proteasome/protease-like
      activity factor by antibodies from humans infected with Chlamydia trachomatis.
AB  - We have previously shown that individuals infected with Chlamydia trachomatis can
      develop a robust antibody response to a chlamydia-secreted protein (designated
      chlamydial proteasome/protease-like activity factor [CPAF]). We now report that
      sera collected from these infected individuals neutralized the proteolytic
      activity of CPAF. Depletion of the serum sample with CPAF proteins to remove the
      CPAF-specific antibodies effectively blocked the neutralization, whereas similar
      depletion with the HSP60 proteins failed to do so. We further demonstrated that
      the CPAF central region covering residues 200 to 338 was predominantly recognized
      by the human neutralization antibodies. The significance of the CPAF
      neutralization antibodies generated in chlamydia-infected individuals is
      discussed.

PMID- 15972541
TI  - Complement depletion renders C57BL/6 mice sensitive to the Bacillus anthracis
      Sterne strain.
AB  - Concerns regarding safety and control of virulent Bacillus anthracis have created
      substantial hurdles to the study of anthrax. The Sterne strain is considered
      relatively safe to study, but this acapsular strain has a defect in normal mice
      and is often studied in A/J mice. A/J mice are highly susceptible to the Sterne
      strain, due to a defect in the Hc locus, which encodes complement factor 5 (C5).
      Here we show that normally resistant C57BL/6 mice become highly susceptible to
      the Sterne strain upon complement depletion with cobra venom factor. This
      generalizable approach should allow the virulence of anthrax to be studied under
      relatively safe conditions and using a wide variety of mouse strains.

PMID- 15972542
TI  - Cross-recognition of N-formylmethionine peptides is a general characteristic of
      H2-M3-restricted CD8+ T cells.
AB  - H2-M3-restricted CD8+ T cells can exhibit cross-reactivity to different
      bacterially derived N-formylmethionine peptides. The extent of this promiscuity
      is unclear. We deleted the nonredundant fMIVTLF epitope and found that Listeria
      monocytogenes still primed fMIVTLF-specific T cells. Thus, cross-reactivity
      appears to be a more general characteristic of H2-M3-restricted T cells.

PMID- 15972543
TI  - Endogenous CD4+ CD25+ regulatory T cells play no apparent role in the acute
      humoral response to intact Streptococcus pneumoniae.
AB  - Immunoglobulin G (IgG) antiprotein and antipolysaccharide responses to intact
      Streptococcus pneumoniae are CD4+-T-cell dependent and therefore might be under
      the negative control of CD4+ CD25+ regulatory T cells. Injection of anti
      interleukin 2 receptor alpha (anti-IL-2Ralpha) MAb to deplete regulatory T cells,
      injection of agonistic MAb against glucocorticoid-induced tumor necrosis factor
      receptor family-related protein to inhibit regulatory-T-cell function, and
      adoptive transfer of regulatory-T-cell-depleted CD4+ T cells into athymic nude
      mice each had no effect on either the primary or secondary protein- or
      polysaccharide-specific IgG response to intact S. pneumoniae. Surprisingly, anti
      IL-2Ralpha MAb also had no effect on the IgG response to intact S. pneumoniae in
      MyD88-/- mice or to a soluble protein-polysaccharide conjugate injected into wild
      type mice in the absence of adjuvant. Collectively, these data are the first to
      suggest that, in contrast to their role in limiting chronic cell-mediated
      immunity, regulatory T cells may play no significant role in an acute humoral
      immune response to an intact extracellular bacterial pathogen.

PMID- 15972544
TI  - Protective immunization of mice with an active-site mutant of subtilase cytotoxin
      of Shiga toxin-producing Escherichia coli.
AB  - We have recently described a novel AB(5) cytotoxin produced by certain Shiga
      toxin-producing Escherichia coli strains. The A subunit of this toxin is a
      subtilase-like serine protease, while the B pentamer mediates binding to host
      cell glycolipid receptors. The subtilase cytotoxin is lethal for mice, causing
      extensive microvascular thrombosis as well as necrosis in the brain, kidneys, and
      liver. In the present study, we have immunized mice with a purified derivative of
      the toxin with a Ser272 --> Ala mutation in the A subunit which abolishes
      cytotoxicity. This elicited strong antibody responses, as judged by enzyme-linked
      immunosorbent assay, which conferred protection against intraperitoneal challenge
      with purified toxin. Immunized mice were also protected from weight loss
      resulting from oral challenge with an E. coli K-12 clone expressing the active
      toxin.

PMID- 15972545
TI  - Campylobacter jejuni induces secretion of proinflammatory chemokines from human
      intestinal epithelial cells.
AB  - Campylobacter jejuni is a common cause of diarrhea in humans. While the
      pathogenic mechanisms of C. jejuni are not completely understood, host
      inflammatory responses are thought to be contributing factors. In this report, C.
      jejuni 81-176 is shown to up-regulate chemokines essential to inflammatory
      responses. Growth-related oncogene alpha (GROalpha), GROgamma, macrophage
      inflammatory protein 1, monocyte chemoattractant protein 1 (MCP-1), and gamma
      interferon-inducible protein 10 (gammaIP-10) mRNA transcription in INT-407 cells
      was enhanced within 4 h of bacterial exposure. Infection with viable
      campylobacters was necessary for sustained chemokine transcription and was NF
      kappaB dependent. GROalpha, gammaIP-10, and MCP-1 chemokine secretions were
      confirmed by immunological assays.

PMID- 15972546
TI  - The order of prime-boost vaccination of neonatal calves with Mycobacterium bovis
      BCG and a DNA vaccine encoding mycobacterial proteins Hsp65, Hsp70, and Apa is
      not critical for enhancing protection against bovine tuberculosis.
AB  - Priming neonatal calves at birth with a Mycobacterium bovis bacillus Calmette
      Guerin (BCG) vaccine and boosting with a DNA vaccine consisting of plasmids
      encoding mycobacterial antigens Hsp65, Hsp70, and Apa or the reverse prime-boost
      sequence induced similar levels of protection against experimental challenge with
      Mycobacterium bovis. When M. bovis was isolated from a thoracic lymph node
      following challenge, the two groups of calves given the prime-boost regimen had
      significantly lower numbers of M. bovis isolates than those vaccinated with BCG
      alone. These observations suggest that the exact sequence of administration of a
      prime-boost vaccination regimen in a neonatal animal model is not critical to the
      development of immunity.

PMID- 15972547
TI  - Genome scale identification of Treponema pallidum antigens.
AB  - Antibody responses for 882 of the 1,039 proteins in the proteome of Treponema
      pallidum were examined. Sera collected from infected rabbits were used to
      systematically identify 106 antigenic proteins, including 22 previously
      identified antigens and 84 novel antigens. Additionally, sera collected from
      rabbits throughout the course of infection demonstrated a progression in the
      breadth and intensity of humoral immunoreactivity against a representative panel
      of T. pallidum antigens.

PMID- 15972548
TI  - Structural diversity of streptokinase and activation of human plasminogen.
AB  - The beta domain of streptokinase is required for plasminogen activation and
      contains a region of sequence diversity associated with infection and disease in
      group A streptococci. We report that mutagenesis of this polymorphic region does
      not alter plasminogen activation, which suggests an alternative function for this
      molecular motif in streptococcal disease.

PMID- 15972550
TI  - The cover. Meditation by the Sea.

PMID- 15972549
TI  - Certain site-directed, nonenzymatically active mutants of the Haemophilus
      influenzae P4 lipoprotein are able to elicit bactericidal antibodies.
AB  - The Haemophilus influenzae P4 lipoprotein (hel) is a potential component of a
      nontypeable H. influenzae otitis media vaccine. Since P4 is known to be an
      enzyme, nonenzymatically active forms of recombinant P4 are required. After site
      directed mutagenesis of the hel gene, three of the mutated proteins were shown to
      be vaccine candidates.

PMID- 15972551
TI  - Monoclonal antibody therapies shine in breast cancer clinical trials.

PMID- 15972552
TI  - New human retroviruses discovered: evidence that cross-species leap not a rare
      event.

PMID- 15972553
TI  - Scenarios for stem cell creation debated: panel members spar over ethical and
      scientific issues.

PMID- 15972560
TI  - Publicly reporting quality information.

PMID- 15972561
TI  - Obesity in the NFL.

PMID- 15972562
TI  - Association between breastfeeding and likelihood of myopia in children.

PMID- 15972563
TI  - Staphylococcus aureus endocarditis: a consequence of medical progress.
AB  - CONTEXT: The global significance of infective endocarditis (IE) caused by
      Staphylococcus aureus is unknown. OBJECTIVES: To document the international
      emergence of health care-associated S aureus IE and methicillin-resistant S
      aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study set in
      39 medical centers in 16 countries. Participants were a population of 1779
      patients with definite IE as defined by Duke criteria who were enrolled in the
      International Collaboration on Endocarditis-Prospective Cohort Study from June
      2000 to December 2003. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: S
      aureus was the most common pathogen among the 1779 cases of definite IE in the
      International Collaboration on Endocarditis Prospective-Cohort Study (558
      patients, 31.4%). Health care-associated infection was the most common form of S
      aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to
      54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE
      (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was
      more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle
      East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was
      independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval,
      2.9-13.2). Patients in the United States were most likely to be hemodialysis
      dependent, to have diabetes, to have a presumed intravascular device source, to
      receive vancomycin, to be infected with MRSA, and to have persistent bacteremia
      (P<.001 for all comparisons). CONCLUSIONS: S aureus is the leading cause of IE in
      many regions of the world. Characteristics of patients with S aureus IE vary
      significantly by region. Further studies are required to determine the causes of
      regional variation.

PMID- 15972564
TI  - Temporal trends in infective endocarditis: a population-based study in Olmsted
      County, Minnesota.
AB  - CONTEXT: Limited data exist regarding population-based epidemiologic changes in
      incidence of infective endocarditis (IE). OBJECTIVE: To evaluate temporal trends
      in the incidence and clinical characteristics of IE. DESIGN, SETTING, AND
      PATIENTS: Population-based survey using the resources of the Rochester
      Epidemiology Project of Olmsted County, Minnesota. One hundred seven IE episodes
      occurred in 102 Olmsted County residents between 1970 and 2000. The modified Duke
      criteria were used to validate the diagnosis of definite or possible IE. MAIN
      OUTCOME MEASURES: Incidence of IE, proportion of patients with underlying heart
      disease, and causative microorganisms and clinical characteristics. RESULTS: Age-
      and sex-adjusted incidence of IE ranged from 5.0 to 7.0 cases per 100,000 person
      years during the study period and did not change significantly over time (P = .42
      for trend). Infective endocarditis caused by viridans group streptococci was the
      most common organism-specific subgroup, with an annual adjusted incidence of 1.7
      to 3.5 cases per 100,000; in comparison, IE due to Staphylococcus aureus had an
      annual adjusted incidence of 1.0 to 2.2 cases per 100,000. No time trend was
      detected for either pathogen group (P = .63 and P = .66, respectively). An
      increasing temporal trend was observed in the proportions of prosthetic valve IE
      cases (P = .09). Among people with underlying heart disease, there was an
      increasing temporal trend in mitral valve prolapse (P = .04) and a decreasing
      trend in rheumatic heart disease (P = .08). However, the absolute numbers were
      small. There was no time trend in rates of valve surgery or 6-month mortality
      during the study period (P = .97 and P = .59, respectively). CONCLUSIONS: In this
      community-based temporal trend study, we found no substantial change in the
      incidence of IE over the past 3 decades. Viridans group streptococci continue to
      outnumber S aureus as the most common causative organisms of IE in this
      population.

PMID- 15972565
TI  - Information leaflet and antibiotic prescribing strategies for acute lower
      respiratory tract infection: a randomized controlled trial.
AB  - CONTEXT: Acute lower respiratory tract infection is the most common condition
      treated in primary care. Many physicians still prescribe antibiotics; however,
      systematic reviews of the use of antibiotics are small and have diverse
      conclusions. OBJECTIVE: To estimate the effectiveness of 3 prescribing strategies
      and an information leaflet for acute lower respiratory tract infection. DESIGN,
      SETTING, AND PATIENTS: A randomized controlled trial conducted from August 18,
      1998, to July 30, 2003, of 807 patients presenting in a primary care setting with
      acute uncomplicated lower respiratory tract infection. Patients were assigned to
      1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic
      groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics).
      INTERVENTION: Three strategies, immediate antibiotics (n = 262), a delayed
      antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were
      prescribed. Approximately half of each group received an information leaflet (129
      for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for
      no antibiotics). MAIN OUTCOME MEASURES: Symptom duration and severity. RESULTS: A
      total of 562 patients (70%) returned complete diaries and 78 (10%) provided
      information about both symptom duration and severity. Cough rated at least "a
      slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting >
      or =17 days). An information leaflet had no effect on the main outcomes. Compared
      with no offer of antibiotics, other strategies did not alter cough duration
      (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate,
      0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the
      immediate antibiotic group, slightly fewer patients in the delayed and control
      groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients
      were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer
      patients believed in the effectiveness of antibiotics (75%, 40%, and 47%,
      respectively; P<.001). There were lower reattendances within a month with
      antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and
      immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances
      for no leaflet, 0.11; and leaflet, 0.17; P = .02). CONCLUSION: No offer or a
      delayed offer of antibiotics for acute uncomplicated lower respiratory tract
      infection is acceptable, associated with little difference in symptom resolution,
      and is likely to considerably reduce antibiotic use and beliefs in the
      effectiveness of antibiotics.

PMID- 15972567
TI  - Efficacy and safety of opioid agonists in the treatment of neuropathic pain of
      nonmalignant origin: systematic review and meta-analysis of randomized controlled
      trials.
AB  - CONTEXT: In the United States, an estimated 2 million persons have neuropathic
      pain that is often resistant to therapy. The use of opioids for neuropathic pain
      remains controversial, in part because studies have been small, have yielded
      equivocal results, and have not established the long-term risk-benefit ratio of
      this treatment. OBJECTIVE: To assess the efficacy and safety of opioid agonists
      for the treatment of neuropathic pain based on published randomized controlled
      trials (RCTs). DATA SOURCES: We searched MEDLINE (1966 to December 2004) and the
      Cochrane Central Register of Controlled Trials (fourth quarter, 2004) for
      articles in any language, along with reference lists of reviews and retrieved
      articles, using a combination of 9 search terms for RCTs with 32 terms for
      opioids and 15 terms for neuropathic pain. STUDY SELECTION: Trials were included
      in which opioid agonists were given to treat central or peripheral neuropathic
      pain of any etiology, pain was assessed using validated instruments, and adverse
      events were reported. Studies in which drugs other than opioid agonists were
      combined with opioids or opioids were administered epidurally or intrathecally
      were excluded. DATA EXTRACTION: Data were extracted by 2 independent
      investigators and included demographic variables, diagnoses, interventions,
      efficacy, and adverse effects. DATA SYNTHESIS: Twenty-two articles met inclusion
      criteria and were classified as short-term (less than 24 hours; n = 14) or
      intermediate-term (median = 28 days; range = 8-56 days; n = 8) trials. The short
      term trials had contradictory results. In contrast, all 8 intermediate-term
      trials demonstrated opioid efficacy for spontaneous neuropathic pain. A fixed
      effects model meta-analysis of 6 intermediate-term studies showed mean
      posttreatment visual analog scale scores of pain intensity after opioids to be 14
      units lower on a scale from 0 to 100 than after placebo (95% confidence interval
      [CI], -18 to -10; P<.001). According to number needed to harm (NNH), the most
      common adverse event was nausea (NNH, 3.6; 95% CI, 2.9-4.8), followed by
      constipation (NNH, 4.6; 95% CI, 3.4-7.1), drowsiness (NNH, 5.3; 95% CI, 3.7-8.3),
      vomiting (NNH, 6.2; 95% CI, 4.6-11.1), and dizziness (NNH, 6.7; 95% CI, 4.8
      10.0). CONCLUSIONS: Short-term studies provide only equivocal evidence regarding
      the efficacy of opioids in reducing the intensity of neuropathic pain.
      Intermediate-term studies demonstrate significant efficacy of opioids over
      placebo for neuropathic pain, which is likely to be clinically important.
      Reported adverse events of opioids are common but not life-threatening. Further
      RCTs are needed to establish their long-term efficacy, safety (including
      addiction potential), and effects on quality of life.

PMID- 15972566
TI  - Risk of lung cancer among white and black relatives of individuals with early
      onset lung cancer.
AB  - CONTEXT: Evidence exists that lung cancer aggregates in families and recent
      findings of a chromosomal region linked to lung cancer susceptibility support a
      genetic component to risk. Family studies of early-onset lung cancer patients
      offer a unique opportunity to evaluate lifetime risk of lung cancer in relatives.
      OBJECTIVE: To measure lung cancer aggregation and estimate lifetime risk among
      relatives of early-onset cases and population-based controls. DESIGN AND SETTING:
      Familial aggregation and cumulative risk estimates from interview data of
      incident cases and concurrently ascertained controls between 1990 and 2003 in
      metropolitan Detroit, Mich. PARTICIPANTS: The study included 7576 biological
      mothers, fathers, and siblings of 692 early-onset cases and 773 frequency-matched
      controls. One third of the population was black. MAIN OUTCOME MEASURES:
      Cumulative lifetime risk of lung cancer, stratified by race and smoking behavior
      in relatives of early-onset cases and controls. RESULTS: Smokers with a family
      history of early-onset lung cancer in a first-degree relative had a higher risk
      of developing lung cancer with increasing age than smokers without a family
      history. An increase in risk occurs after age 60 years in these individuals, with
      17.1% (SE 2.4%) of white case relatives and 25.1% (SE 5.8%) of black case
      relatives diagnosed with lung cancer by age 70 years. Relatives of black cases
      were at statistically significant increased risk of lung cancer compared with
      relatives of white cases (odds ratio, 2.07, 95% confidence interval, 1.29-3.32)
      after adjusting for age, sex, pack-years, pneumonia, and chronic obstructive lung
      disease. CONCLUSIONS: First-degree relatives of black individuals with early
      onset lung cancer have greater risk of lung cancer than their white counterparts,
      and these risks are further amplified by cigarette smoking. These data provide
      estimates of lung cancer risk that can be used to offer counseling to family
      members of patients with early-onset lung cancer.

PMID- 15972568
TI  - Pharmacological therapy of lupus nephritis.
AB  - Kidney involvement is common in systemic lupus erythematosus, occurring in up to
      60% of affected adults during the course of their disease. Diffuse proliferative
      lupus nephritis (World Health Organization class IV), the most ominous variant,
      has traditionally been treated with cyclophosphamide and glucocorticoids. With
      cyclophosphamide, women of childbearing potential must weigh the risks of
      sustained amenorrhea, infertility, increased susceptibility to infection, bone
      marrow suppression, hemorrhagic cystitis, and malignancy against the benefits of
      better disease control compared with glucocorticoids alone. Because of the host
      of adverse effects associated with cyclophosphamide, alternative approaches to
      the treatment of lupus nephritis are desirable. A 31-year-old woman developed
      class IV lupus nephritis in the postpartum period. Seeking to preserve fertility
      and avoid other known toxicities of cyclophosphamide, she chose to undergo
      therapy with mycophenolate mofetil. In the treatment of severe lupus nephritis,
      mycophenolate mofetil has emerged as an alternative to cyclophosphamide, offering
      a major advance in the therapy of lupus nephritis.

PMID- 15972569
TI  - Infective endocarditis: global, regional, and future perspectives.

PMID- 15972570
TI  - Antibiotic prescribing for cough and symptoms of respiratory tract infection: do
      the right thing.

PMID- 15972572
TI  - JAMA patient page. Systemic lupus erythematosus.

PMID- 15972573
TI  - An ovulatory gonadotropin stimulus increases cytosolic phospholipase A2
      expression and activity in granulosa cells of primate periovulatory follicles.
AB  - CONTEXT: Prostaglandins (PGs) produced within ovarian follicles in response to
      the ovulatory gonadotropin surge are essential for follicle rupture and oocyte
      release. Arachidonic acid, the common precursor for PG synthesis, is cleaved from
      membrane phospholipids via the activity of phospholipase A2 (PLA2). OBJECTIVE:
      The purpose of this study was to determine which PLA2 form(s) is involved in PG
      production by primate periovulatory follicles. DESIGN AND INTERVENTIONS:
      Gonadotropins were administered to cynomolgus monkeys to stimulate multiple
      follicular development; human chorionic gonadotropin (hCG) initiated
      periovulatory events. Granulosa cells and whole ovaries were obtained before (0
      h), and 12, 24, and 36 h after hCG administration. PATIENTS: Granulosa-lutein
      cells were also obtained from women undergoing infertility treatment. OUTCOME
      MEASURES AND RESULTS: mRNA for cytosolic (c)PLA2 and secretory (s)PLA2V, but not
      sPLA2IIA, was expressed by granulosa cells. cPLA2 mRNA levels were low at 0 h,
      elevated by 12 h, and remained high 24-36 h after hCG administration. sPLA2V mRNA
      levels were low at 0 h and did not change in response to hCG. cPLA2 and sPLA2V
      were detected by immunocytochemistry in granulosa cells of periovulatory
      follicles before and at all times after hCG administration. PLA2 activity was low
      in lysates of granulosa cells obtained 0-24 h after hCG and was elevated in
      granulosa cells obtained 36 h after hCG administration. A cPLA2-selective
      inhibitor decreased both PLA2 activity in monkey granulosa cell lysates and PGE2
      accumulation in cultures of human granulosa-lutein cells. CONCLUSIONS: cPLA2 is
      primarily or exclusively responsible for the gonadotropin-stimulated mobilization
      of arachidonic acid necessary for PG production by primate periovulatory
      follicles.

PMID- 15972574
TI  - Breast inflammatory gigantomastia in a context of immune-mediated diseases.
AB  - CONTEXT: Localized breast lesions have been described in lupic or diabetic
      patients. However, the description of breast gigantomastia in women presenting
      with autoimmune diseases has not been reported. SETTING: The study took place
      within the Department of Endocrinology and Reproductive Medicine, Necker
      Hospital, Paris, France. PATIENTS: We describe eight patients with inflammatory
      gigantomastia, occurring in a context of immune-mediated diseases: myasthenia,
      chronic arthritis, or thyroiditis. MAIN OUTCOME MEASURES: Together with hormonal,
      immunological, and breast magnetic resonance imaging (MRI) evaluation, breast
      histology enabled us to perform immunocytochemical and indirect
      immunofluorescence studies. Control sera were obtained from patients with (n =
      10) and without (n = 7) antinuclear antibodies. RESULTS: Six of the eight
      patients developed gigantomastia either at puberty or during pregnancy. Neither a
      hormonal oversecretion nor a specific immunological pattern was observed. All
      patients except one presented antinuclear antibodies. Histological study revealed
      a diffuse, stromal hyperplasia and a severe atrophy of the lobules. A rarefaction
      of adipocytes was also noted, as previously suggested on MRI. There was a
      perilobular lymphocytic infiltrate made of CD3+ lymphocytes. Study of sera from
      five of six cases of gigantomastia showed a nuclear immunofluorescence pattern in
      normal mammary ductal and lobular glandular epithelium, as well as in kidney and
      intestine epithelial cells. In control sera, a nuclear signal was observed only
      when antinuclear antibodies were present. CONCLUSIONS: We suggest that breast
      tissue may be a target tissue in autoimmune diseases, this process being favored
      by the hormonal milieu. However, the precise mechanism of such association is not
      individualized. The fact that stromal hyperplasia is the main histological
      feature justifies the search for the involvement of growth factors in such a
      process.

PMID- 15972575
TI  - Effects of dietary carbohydrate restriction with high protein intake on protein
      metabolism and the somatotropic axis.
AB  - CONTEXT: Alterations in dietary macronutrient intake can influence protein
      turnover. OBJECTIVE: The purpose of this study was to assess the influence of a
      low-carbohydrate/high-protein diet (LC/HP) on skeletal muscle protein synthesis
      and whole-body proteolysis, without the confounding influence of a negative
      energy balance. DESIGN: Nine-day dietary intervention was applied. SETTING:
      Subjects remained in the General Clinical Research Center throughout the 9-d
      study. PARTICIPANTS: Eight young, healthy volunteers participated. INTERVENTION:
      Subjects ate a typical Western diet (60% carbohydrate, 30% fat, 10% protein) for
      2 d, followed immediately by 7 d of an isocaloric LC/HP (5% carbohydrate, 60%
      fat, 35% protein). MAIN OUTCOME MEASURES: Skeletal muscle fractional synthetic
      rate and whole-body proteolysis [leucine rate of appearance in plasma (Ra)] were
      measured after an overnight fast before and after 2 and 7 d of LC/HP. We also
      measured plasma concentrations of insulin, GH, and IGF-I. RESULTS: Leucine Ra was
      increased (P = 0.03) after 2 and 7 d of LC/HP, and muscle fractional synthetic
      rate was approximately 2-fold higher (P < 0.01) after 7 d of LC/HP. Fat free mass
      was not altered by LC/HP. Average 24-h plasma insulin concentration was 50% lower
      (P < 0.001) after 2 and 7 d of LC/HP, whereas GH secretion and total plasma IGF-I
      concentrations were unchanged with LC/HP. However, plasma free IGF-I decreased by
      approximately 30% after 7 d of LC/HP (P = 0.002), whereas muscle IGF-I mRNA
      increased about 2-fold (P = 0.05). CONCLUSIONS: Increasing dietary protein
      content during a 7-d carbohydrate restricted diet stimulated muscle protein
      synthesis and whole-body proteolysis without a measurable change in fat free
      mass.

PMID- 15972576
TI  - A single recombinant human thyrotropin-stimulated serum thyroglobulin measurement
      predicts differentiated thyroid carcinoma metastases three to five years later.
AB  - CONTEXT: Testing for residual differentiated thyroid carcinoma relies heavily
      upon recombinant human (rh)TSH-stimulated serum thyroglobulin (Tg) levels, but
      the positive predictive value is often low. OBJECTIVE: Our objective was to
      determine the accuracy of a single rhTSH-Tg measurement over time. DESIGN AND
      SETTING: We conducted a prospective follow-up study at the University referral
      center. PATIENTS: A total of 107 differentiated thyroid carcinoma patients were
      stratified according to their initial rhTSH-Tg as follows: group 1 with Tg less
      than 0.5 (n = 68), group 2 with Tg of 0.6-2.0 (n = 19), and group 3 with Tg
      greater than 2 ng/ml (n = 20). INTERVENTION: Clinical evaluations were conducted
      over 0.9-5.2 yr as follows: Tg during thyroid hormone suppression (n = 27), after
      rhTSH (n = 59), and/or after thyroid hormone withdrawal (n = 15). MAIN OUTCOME:
      Tumor was identified in one patient in each of groups 1 (1.6%) and 2 (5.5%), and
      16 in group 3 (80%), comprising 19 tumor locations: 11 locoregional, two
      mediastinal, five lung, and one brain. Tumor was found in 81% with an initial or
      follow-up rhTSH-Tg greater than 2 ng/ml. TSH-stimulated Tg fell spontaneously to
      less than 0.5 ng/ml in 50% of group 2 and 5% of group 3 over 1.7-5.0 yr. The
      positive predictive value of the initial rhTSH-Tg greater than 2 ng/ml was 80%,
      and the negative predictive value was 98%. After retreatment, 100% of group 1,
      74% of group 2, and 55% of group 3 had no evidence of tumor (P = 0.0001).
      CONCLUSIONS: 1) A single rhTSH-Tg greater than 2 ng/ml predicts persistent tumor,
      although no value entirely excludes future recurrence. 2) Repeated TSH-stimulated
      studies are appropriate for patients at risk of recurrence, especially those with
      an rhTSH-Tg greater than 1 ng/ml. 3) A single rhTSH-Tg less than 0.5 ng/ml
      without Tg antibody has an approximately 98% likelihood of identifying patients
      completely free of tumor, a large group in which TSH suppression to less than 0.1
      mIU/liter and frequent imaging and TSH-stimulated Tg testing are unnecessary.

PMID- 15972577
TI  - Primary empty sella.
AB  - CONTEXT: The term primary empty sella (PES) refers to a number of endocrine
      and/or neurological disturbances that may be caused by the herniation of
      subarachnoid space within the sella. SETTING: The records of all patients with a
      diagnosis of empty sella between 1985 and 2002 seen at the Catholic University of
      Rome and University of Brescia were examined retrospectively. PATIENTS: We have
      observed 171 female and 42 male patients affected by PES (over 4:1 sex ratio).
      The mean age at diagnosis in our subjects was 51.8 +/- 2.1 yr. Mean body mass
      index was 27.3 +/- 3.5 kg/m2. MAIN OUTCOME MEASURE: All the patients have been
      analyzed first either with sellar computed tomography scan or magnetic resonance
      imaging. All patients underwent neurological, ophthalmological, and baseline
      endocrine evaluation (appropriate stimulation tests were performed when
      hypopituitarism was suspected). RESULTS: In the overall population, 40 of 213
      patients had documented endocrine abnormalities, specifically 31 females and nine
      males. Twenty-two patients (10.3% of total patients; 18 women, 10.5% of all
      women, with a mean age of 38.6 +/- 1.1 yr and four males, with a mean age 46.5 +/
      3.52 yr) presented with hyperprolactinemia. Global anterior hypopituitarism was
      confirmed in nine patients. Eight patients presented an isolated GH deficiency.
      One hundred thirty-eight of our patients presented a so-called partial empty
      sella at computed tomography scan/magnetic resonance imaging, and 75 had total
      PES. CONCLUSIONS: PES may be associated with variable clinical conditions ranging
      from mild endocrine disturbances to severe intracranial hypertension and
      rhinorrhea. The need for treatment of hyperprolactinemia as well as for
      replacement hormone therapy must be assessed in PES. Symptomatic intracranial
      hypertension makes cerebrospinal fluid shunting procedures necessary.

PMID- 15972578
TI  - Overexpression of the Wnt5b gene in leiomyoma cells: implications for a role of
      the Wnt signaling pathway in the uterine benign tumor.
AB  - CONTEXT: Uterine leiomyomas are the most common tumors in the human female pelvis
      and the leading indication for pelvic surgery. The molecular causes of the
      disease remain unknown. OBJECTIVE: Using an oligonucleotide microarray-based
      hybridization analysis, we observed that a Wnt family member transcript, Wnt5b,
      was overexpressed in smooth muscle cells (SMC) derived from leiomyomas when
      compared with matched myometrial cells. Based on this finding and on previous
      observations, we have hypothesized that altered expression of specific Wnt family
      members might be involved in leiomyoma formation and/or growth. MAIN OUTCOME
      MEASURES: The expression patterns of two members of the Wnt pathway, Wnt5b and
      secreted frizzled related protein (sFRP)1, were evaluated in myometrial SMC (n =
      22) and in leiomyoma cells (n = 27) by real-time quantitative PCR. In addition,
      regulation of expression of the two molecules was examined. RESULTS: Compared
      with myometrial SMC, cells derived from leiomyomas had significantly higher
      levels of both Wnt5b and sFRP1 transcripts. When the data were analyzed as a
      function of the phase of the menstrual cycle, no significant difference in sFRP1
      mRNA levels could be detected, whereas levels of Wnt5b transcript were
      significantly higher in the secretory phase in myometrial cells. Treatment with 9
      cis retinoic acid significantly inhibited Wnt5b expression in myometrial SMC but
      not in their leiomyoma counterparts. CONCLUSIONS: Specific Wnt signaling genes
      are overexpressed in leiomyoma cells. Moreover, in these cells, the regulation of
      Wnt5b expression by retinoids appears to be attenuated.

PMID- 15972579
TI  - Association of mitochondrial deoxyribonucleic acid 16189 variant (T->C
      transition) with metabolic syndrome in Chinese adults.
AB  - OBJECTIVE: A common variant in mitochondrial DNA (mtDNA) at bp 16189 (T-->C
      transition) has been associated with small birth size, adulthood hyperglycemia,
      and insulin resistance in Caucasians. In this study, we investigated whether
      mtDNA 16189 variant is associated with metabolic syndrome in Chinese subjects.
      METHODS: Six hundred fifteen Chinese adults, aged 40 yr or older, were recruited
      in this study. The 16189 variant of mtDNA was detected using PCR and restriction
      enzyme digestion. Metabolic syndrome was diagnosed on modified National
      Cholesterol Education Program Adult Treatment Panel III guidelines, using body
      mass index (BMI) instead of waist circumference. An association study was
      performed with chi2 test and logistic regression analysis. RESULTS: The
      prevalence of the 16189 variant was higher in patients with metabolic syndrome
      than in those without: 44% (125 of 284) vs. 33.2% (110 of 331) (P = 0.006). The
      association between this 16189 variant of mtDNA and metabolic syndrome (P =
      0.021) remained significant even after correcting for age and BMI. As to the
      individual traits, the prevalence of fasting plasma glucose of at least 110 mg/dl
      (> or =6.1 mmol/liter) [(51.5% (121 of 235) vs. 42.1% (160 of 380); P = 0.023],
      type 2 diabetes mellitus [48.1% (113 of 235) vs. 39.2% (149 of 380); P = 0.031],
      and hypertriglyceridemia [44.3% (104 of 235) vs. 35.8% (136 of 380); P = 0.037]
      were significantly higher in subjects harboring the 16189 variant of mtDNA than
      those with the wild type. However, the prevalence of hypertension [53.2% (125 of
      235) vs. 47.6% (181 of 380); P = 0.180], BMI greater than 25 kg/m2 [48.5% (114 of
      235) vs. 43.9% (167 of 380); P = 0.270], and low high-density lipoprotein
      cholesterol [61.3% (144 of 235) vs. 54.7% (208 of 380); P = 0.111] did not reach
      a significant difference between the two groups. Furthermore, there was a trend
      of increasing frequency of occurrence of the 16189 variant in individuals having
      an increasing number of components of metabolic syndrome (Ptrend < 0.005).
      CONCLUSION: Our data strongly suggest that mtDNA 16189 variant underlies
      susceptibility to metabolic syndrome in the Chinese population.

PMID- 15972580
TI  - A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under
      vitamin D supplementation: a randomized, double-blind, placebo-controlled
      clinical trial.
AB  - CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in
      osteoporotic subjects. However, vitamin D insufficiency might have influenced the
      effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can
      increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN,
      SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo
      controlled clinical trial of 219 osteoporotic patients (49-87 yr of age).
      INTERVENTIONS: Subjects were randomly assigned to receive placebo or 0.5, 0.75,
      or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d
      vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD
      and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71
      treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8%
      vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71,
      respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8,
      0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5,
      0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption
      markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0
      microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in
      7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups,
      respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS:
      These results demonstrate that ED-71 treatment at around 0.75 microg/d can
      effectively and safely increase lumbar and hip BMD in osteoporotic patients with
      vitamin D supplementation.

PMID- 15972581
TI  - Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in
      adults with acquired structural hypothalamic damage?
AB  - CONTEXT: Obesity is a common sequel to hypothalamic tumors and their treatment,
      but the underlying mechanisms are not fully established. OBJECTIVE: Our objective
      was to evaluate the role of ghrelin and peptide-YY (PYY) in human hypothalamic
      obesity. SETTING: The study took place at a University Medical Center.
      PARTICIPANTS: Subjects included 14 adult patients (six male, eight female) with
      tumors of the hypothalamic region and 15 healthy controls (six male and nine
      female) matched for age, body mass index, and percentage of body fat.
      INTERVENTIONS: Plasma ghrelin and total PYY were measured using RIAs after an
      overnight fast and 15, 30, 60, 120, and 180 min after a mixed meal. MAIN OUTCOME
      MEASURES: We assessed ghrelin, PYY, and appetite ratings. RESULTS: The fall in
      ghrelin levels after the test meal was similar in the two groups. There was no
      statistically significant change postprandially in circulating PYY in the
      patients with hypothalamic damage. Fasting leptin levels and postprandial insulin
      responses were also similar in the two groups. Patients with hypothalamic damage
      reported higher hunger ratings at 3 h after the meal (P = 0.01) and a stronger
      desire to eat at 2 h (P = 0.01) and 3 h (P = 0.02) compared with the control
      group. CONCLUSIONS: Adult patients with structural hypothalamic damage show
      impaired satiety, but the changes observed in circulating ghrelin and PYY
      concentrations in response to a test meal do not indicate a central role for
      these gut hormones in the control of appetite and the pathogenesis of obesity in
      these patients.

PMID- 15972582
TI  - Monthly oral ibandronate is well tolerated and efficacious in postmenopausal
      women: results from the monthly oral pilot study.
AB  - CONTEXT: Ibandronate, a potent, nitrogen-containing bisphosphonate developed for
      intermittent administration in postmenopausal osteoporosis, aims to overcome
      current adherence issues with daily and weekly oral bisphosphonates through once
      monthly oral dosing. OBJECTIVE: The purpose of this study was to investigate the
      safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate.
      DESIGN: A randomized, 3-month, double-blind, placebo-controlled, phase I study
      (Monthly Oral Pilot Study) was conducted. SETTING: The study was conducted at
      five clinical trial centers in the United Kingdom and Belgium. PATIENTS OR OTHER
      PARTICIPANTS: Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post
      menopause; n = 144). INTERVENTION(S): Once-monthly oral ibandronate 50, 100, or
      150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with
      participants continuing on either 50 or 100 mg. MAIN OUTCOME MEASURE(S): Primary
      outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum
      ibandronate AUC0-infinity. RESULTS: Once-monthly oral ibandronate was well
      tolerated, with a similar overall and upper gastrointestinal safety profile to
      placebo. Once-monthly ibandronate was also highly effective in decreasing bone
      turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in
      the 150- and 100-mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (
      54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30
      d after the final dose). Analysis of the area under the effect curve (d 1-91) for
      change from baseline (percent x days) in serum CTX and urinary CTX indicated a
      dose-response relationship. The AUC0-infinity for ibandronate increased with dose
      but not in a dose-proportional manner. CONCLUSIONS: These findings indicate a
      potential role for once-monthly oral ibandronate in the treatment of
      postmenopausal osteoporosis.

PMID- 15972584
TI  - Lipopolysaccharide heterogeneity: innate host responses to bacterial modification
      of lipid a structure.
AB  - The innate host response system is composed of various mechanisms designed to
      detect and facilitate host responses to microbial components, such as
      lipopolysaccharides (LPS). To enable this to occur, innate systems contain
      multiple pattern recognition receptors (i.e., LBP, CD14, and TLRs), which
      identify certain features within bacterial LPS that are foreign to the host, as
      well as essential and uniquely specific for bacteria. Innate host identification
      of unique bacterial components or patterns, therefore, relies on the inability of
      bacteria to alter these essential or critical components dramatically.
      Historically, LPS have been viewed as essential outer-membrane molecules
      containing both a highly variable outer region (O-segment) as well as a
      relatively conserved inner region (lipid A). However, over the last decade, new
      evidence has emerged, revealing that increased natural diversity or heterogeneity
      within specific components of LPS, such as lipid A-resulting in minor to moderate
      changes in lipid A structure-can produce dramatic host responses. Therefore,
      examples of natural lipid A heterogeneity, and the mechanisms that control it,
      represent a novel approach in which bacteria modulate host responses and may
      thereby confer specific advantages to certain bacterial species under changing
      environmental host conditions.

PMID- 15972585
TI  - Drug-induced disorders of teeth.
AB  - It is essential that every health care professional who is involved with the
      prescription or recommendation of drugs be fully aware of any resultant disorders
      that may arise as a side-effect. A range of drugs can affect the teeth. In this
      review article, drugs that have the potential to induce changes in teeth have
      been classified as those leading to tooth discoloration (intrinsic and
      extrinsic), physical damage to tooth structure (enamel, dentin, and cementum),
      and alteration in tooth sensitivity.

PMID- 15972586
TI  - Organized tooth-specific cellular differentiation stimulated by BMP4.
AB  - Mammalian teeth develop on the oral surface of the first pharyngeal arch by a
      series of reciprocal interactions between epithelial and mesenchymal cells. The
      embryonic first pharyngeal arch oral epithelium is able to induce tooth formation
      when combined with mesenchymal cells from the second pharyngeal arch, a region
      devoid of tooth development. Second pharyngeal arch mesenchyme is thus competent
      to form teeth if provided with the correct signals. First-arch oral epithelium
      expresses several signaling molecules that could be potential inducers of tooth
      development, including BMP4. The addition of BMP4 to intact second-arch explants
      resulted in the development of organized structures containing layers of cells
      that express marker genes of tooth-specific cells, odontoblasts and ameloblasts.
      Thus, although overt tooth development did not occur, BMP4 has the ability to
      stimulate organized differentiation of epithelial- and mesenchymal-derived dental
      specific cells from non-dental primordia.

PMID- 15972587
TI  - Transglutaminase crosslinking of SIBLING proteins in teeth.
AB  - Transglutaminase 2 (TG2), a protein-crosslinking enzyme, participates in
      extracellular matrix maturation and cell adhesion in cartilage and bone. We
      hypothesized that TG2 has similar roles in teeth. A TG activity assay and
      immunoblotting of rat tooth extracts showed TG activity and the presence of high
      molecular-weight forms of the SIBLING (Small Integrin-Binding LIgand N-linked
      Glycoprotein) proteins: dentin matrix protein 1 (DMP1), dentin phosphoprotein
      (DPP), and bone sialoprotein (BSP). DMP1 and BSP, each containing both glutamine
      and lysine residues critical for crosslink formation, readily formed polymers in
      vitro when incubated with TG2. The ability of glutamine-lacking DPP to form
      polymers in vitro and in vivo demonstrates that it could act as a lysine donor
      for crosslinking, potentially having protein crosslinking partner(s) in teeth.
      Consistent with a role in cell adhesion, the TG2 isoform was co-localized by
      immunohistochemistry with its substrates at cell-matrix adhesion sites, including
      along odontoblast tubules (DMP1 and DPP), in the pericellular matrix of
      cementocytes (DMP1), and in predentin (BSP).

PMID- 15972588
TI  - Mouse amelogenin exons 8 and 9: sequence analysis and protein distribution.
AB  - Amelogenin is the major protein of the developing enamel. Two additional exons,
      termed 8 and 9, have been characterized in the rat. Our aim was: to identify the
      mouse amelogenin exons 8/9 sequences; to investigate the potential presence of
      the alternative spliced isoforms of amelogenin exons 8/9; and to immunolocalize
      proteins containing sequences encoded by exons 8/9 during odontogenesis. RT-PCR
      analysis with exon 9 anti-sense primer generated 2 major amplicons with the use
      of a mouse tooth cDNA library and dental cell lines. DNA sequence analysis showed
      93% identify with the rat exons 8/9 sequence. Alternative splicing of exon 3 was
      also found, but only in cDNAs lacking exons 8 and 9. Immunohistochemistry
      localized exons 8/9-encoded proteins in ameloblasts, young odontoblasts, and
      stratum intermedium cells. Analysis of our data supports the hypothesis that: (1)
      AMELX contains 2 additional exons; (2) ameloblasts and odontoblasts synthesize
      amelogenin 8/9; and (3) amelogenin splice variants may have unique functions
      during tooth formation.

PMID- 15972589
TI  - NO-cGMP signaling molecules in cells of the rat molar dentin-pulp complex.
AB  - By the formation of cyclic guanosine 3',5'-monophosphate (cGMP), nitric oxide
      (NO)-sensitive enzyme-soluble guanylate cyclase (sGC) plays a receptor role for
      NO within the NO-cGMP signaling cascade, which is involved in vasodilatation and
      neurotransmission. The hypothesis that NO-cGMP signaling molecules modulate cells
      of the dentin-pulp complex was investigated in rat molars by histochemical,
      immunohistochemical, immuno-ultrastructural, and organ bath techniques. NO
      synthase (NOS) I-III, the sGC alpha(2)-subunit/beta(1)-subunit, and cGMP were
      detected in odontoblasts and blood vessels. NOS I, sGC alpha(2), and cGMP were
      identified in nerve fibers. Treatment of rat molars with the NO donor NONOate
      (10(-5) M) increased cGMP staining intensities in blood vessels and odontoblasts,
      while NO synthase inhibitor L-NAME (10(-4) M) attenuated intensity of the
      reaction products for cGMP, suggesting an effect of endogenous NO on sGC. These
      correlations of patterns and alterations of cGMP staining intensities after
      treatment with the NO donor or NO inhibitor might represent an NO-sGC-cGMP
      signaling-dependent modulation of odontoblasts, blood vessels, and nerve fibers
      in the dentin-pulp complex.

PMID- 15972590
TI  - Suppression of stress-induced nNOS expression in the rat hypothalamus by biting.
AB  - Nitric oxide (.NO) modulates the activity of the endocrine system in the
      behavioral response to stress. The purpose of this study was to investigate the
      effect of restraining the body of an animal on expression of neuronal nitric
      oxide synthase (nNOS) in the paraventricular nucleus (PVN) of the hypothalamus,
      and the inhibitory effect of para-masticatory activity on restraint-induced nNOS
      expression. We observed an increase in nNOS mRNA expression and nNOS-positive
      neurons in the rat hypothalamus after 30 or 60 min of restraint. Biting on a
      wooden stick during bodily restraint decreased nNOS mRNA expression in the
      hypothalamus. In addition, the number of nNOS-positive neurons was significantly
      reduced in the PVN of the hypothalamus. These observations clearly suggest a
      possible anti-stress effect of the masticatory activity of biting, and this
      mechanism might be unconsciously in operation during exposure to psychological
      stressors.

PMID- 15972591
TI  - Cleavage of PDGF receptor on periodontal ligament cells by elastase.
AB  - Human leukocyte elastase, a neutrophil serine protease, is considered to be a
      potential immunoregulatory protease. Since the PDGF receptor (PDGFR) on
      periodontal ligament (PDL) cells is a crucial element for various functions, such
      as wound healing in periodontal tissue, we investigated the effect of elastase on
      the expression of PDGFR on PDL cells by flow cytometry and Western blotting. We
      found that PDGFR-alpha disappeared with an increasing dose of elastase, and PDGFR
      beta was degraded into several fragments. Elastase degraded both receptors on
      fixed cells, indicating that the degradation resulted from direct proteolysis on
      the cell surface. Elastase also then disturbed the phosphorylation of ERK1/2,
      JNK/SARK, and p38, triggered by PDGF-AA and PDGF-BB, suggesting that elastase
      inhibited PDGFR-dependent cell activation in PDL cells. These results suggest
      that elastase may modulate the PDGF-mediated activity of PDL cells during
      periodontal wound healing.

PMID- 15972592
TI  - PTH(1-34) affects osteoprotegerin production in human PDL cells in vitro.
AB  - Since periodontal ligament (PDL) cells exhibit several osteoblastic traits, we
      hypothesized that human PDL cells will respond to hormonal stimulation in an
      osteoblast-like manner. Confluent and pre-confluent PDL cells from six patients
      were challenged with PTH(1-34). Cell number, ALP, osteocalcin, osteoprotegerin,
      and RANKL expression were determined. Intermittent PTH(1-34) treatment of
      confluent PDL cells caused a significant increase in proliferation, whereas
      differentiation and osteoprotegerin production decreased significantly. In pre
      confluent PDL cells, this treatment regimen induced a biphasic decrease in
      proliferation, but a biphasic increase in differentiation and osteoprotegerin
      production. Continuous PTH(1-34) exposure enhanced proliferation but inhibited
      osteocalcin production in confluent cells and stimulated osteoprotegerin
      production in pre-confluent PDL cells. RANKL was hardly detectable and unaffected
      by PTH(1-34) treatment. These results indicate that human PDL cells respond to
      PTH(1-34) in an osteoblast-like manner, and that the PTH(1-34) effect depends on
      the maturation state of the cells and on the mode of administration.

PMID- 15972593
TI  - Regulatory T-cells infiltrate periodontal disease tissues.
AB  - CD4+CD25+ regulatory T (Tr) cells are critical in regulating the immune response
      and thereby play an important role in the defense against infection and control
      of autoimmune diseases. Our previous studies demonstrated the involvement of
      autoimmune responses in periodontitis. The aim of this study was to identify
      CD4+CD25+ Tr cells in periodontitis tissues and compare them with those in
      gingivitis tissues. Immunohistological analysis of CD4, CD25, and CTLA-4 and the
      gene expression analysis of FOXP3, TGF-beta1, and IL-10 on gingival biopsies
      revealed the presence of CD4+CD25+ Tr cells in all tissues. In periodontitis, the
      percentage of CD4+CD25+ Tr cells increased with increasing proportions of B-cells
      relative to T-cells. FOXP3, a characteristic marker for CD4+CD25+ Tr cells, TGF
      beta1 and IL-10 were expressed more highly in periodontitis compared with
      gingivitis. These findings suggest that CD4+CD25+ Tr cells and possibly other
      regulatory T-cell populations do exist and may play regulatory roles in
      periodontal diseases.

PMID- 15972594
TI  - Effect of occlusal interference on habitual activity of human masseter.
AB  - It has been suggested that occlusal interference may increase habitual activity
      in the jaw muscles and may lead to temporomandibular disorders (TMD). We tested
      these hypotheses by means of a double-blind randomized crossover experiment
      carried out on 11 young healthy females. Strips of gold foil were glued either on
      a selected occlusal contact area (active interference) or on the vestibular
      surface of the same tooth (dummy interference) and left for 8 days each.
      Electromyographic masseter activity was recorded in the natural environment by
      portable recorders under interference-free, dummy-interference, and active
      interference conditions. The active occlusal interference caused a significant
      reduction in the number of activity periods per hour and in their mean amplitude.
      The EMG activity did not change significantly during the dummy-interference
      condition. None of the subjects developed signs and/or symptoms of TMD throughout
      the whole study, and most of them adapted fairly well to the occlusal
      disturbance.

PMID- 15972595
TI  - Validation of the Child Perceptions Questionnaire (CPQ 11-14).
AB  - While the use of adult oral-health-related quality-of-life (OHRQoL) measures in
      supplementing clinical indicators has increased, that for children has lagged
      behind, because of the difficulties of developing and validating such measures
      for children. This study examined the construct validity of the Child Perceptions
      Questionnaire (CPQ(11-14)) in a random sample of 12- and 13-year-old New
      Zealanders. It was hypothesized that children with more severe malocclusions or
      greater caries experience would have higher overall (and subscale domain) CPQ(11
      14) scores. Children (N = 430) completed the CPQ(11-14) and were examined for
      malocclusion (Dental Aesthetic Index) and dental caries. There was a distinct
      gradient in mean CPQ(11-14) scores by malocclusion severity, but there were
      differences across the four subscales. Children in the worst 25% of the DMFS
      distribution had higher CPQ(11-14) scores overall and for each of the 4
      subscales. The construct validity of the CPQ(11-14) appears to be acceptable.

PMID- 15972596
TI  - Water concentration in self-etching primers affects their aggressiveness and
      bonding efficacy to dentin.
AB  - Water is required to ionize acid resin monomers for demineralization of tooth
      substrates. We tested the null hypothesis that altering the water concentration
      in two-step self-etching primers has no effect on their aggressiveness and
      bonding efficacy to dentin. Five experimental self-etching primers were prepared
      with resin-water-ethanol volume ratios of 9-0-1, 8-1-1, 7-2-1, 5-4-1, and 3-6-1.
      They were applied to smear-layer-covered dentin, followed by a bonding resin and
      composite build-ups for microtensile bond testing and TEM examination of tracer
      penetration. Increasing water concentration from 0-60 vol% improved acidic
      monomer ionization that was manifested as increasing hybrid layer thickness.
      However, significantly higher bond strength was observed in the 7-2-1 group, with
      minimal nanoleakage in the corresponding hybrid layer. When self-etching primers
      are formulated, a balance must be achieved to provide sufficient water for
      adequate ionization of the acidic monomers, without lowering the resin
      concentration too much, to optimize their bonding efficacy to dentin.

PMID- 15972597
TI  - Resin composite properties and energy density of light cure.
AB  - According to the "total energy concept", properties of light-cured resin
      composites are determined only by energy density because of reciprocity between
      power density and exposure duration. The kinetics of polymerization is complex,
      and it was hypothesized that degree of cure, flexural strength, and flexural
      modulus were influenced not only by energy density, but also by power density per
      se. A conventional resin composite was cured at 3 energy densities (4, 8, and 16
      J/cm(2)) by 6 combinations of power density (50, 100, 200, 400, 800, and 1000
      mW/cm(2)) and exposure durations. Degree of cure, flexural strength, and flexural
      modulus increased with increasing energy density. For each energy density, degree
      of cure decreased with increasing power density. Flexural strength and modulus
      showed a maximum at intermediate power density. Within clinically relevant power
      densities, not only energy density but also power density per se had significant
      influence on resin composite properties.

PMID- 15972598
TI  - Monomer conversion of pre-heated composite.
AB  - The potential for maximizing conversion of room-temperature, photoactivated resin
      composite in the oral environment is limited. Pre-heating composite prior to
      light-curing is hypothesized to increase monomer conversion and reduce the
      duration of light exposure. Composite temperature was controlled at between 3
      degrees C and 60 degrees C prior to exposure with a conventional quartz-tungsten
      halogen curing unit: 5, 10, 20, or 40 sec. Monomer conversion was calculated from
      infrared spectra at 0 mm (top) and 2-mm-deep surfaces 5 min after light
      initiation. A strong, positive correlation existed between temperature and
      monomer conversion: top r(2) = 0.999, 2 mm r(2) = 0.998. Conversion ranged from
      31.6% (3 degrees C) to 67.3% (60 degrees C). The duration of light exposure,
      reduced by 50 to 75% with pre-heated composite, yielded the same or significantly
      higher conversion (p = 0.001) than with control (22 degrees C, 20 sec). Both
      hypotheses were accepted: Pre-heating composite prior to photoactivation provides
      greater conversion requiring reduced light exposure than with room-temperature
      composite.

PMID- 15972599
TI  - Anode glow discharge plasma treatment of titanium plates facilitates adsorption
      of extracellular matrix proteins to the plates.
AB  - Glow discharge plasma (GDP) supplied to an anode (GDP+) promotes calcium
      phosphate adsorption onto titanium better than that supplied to a cathode (GDP-).
      However, the adsorption of extracellular matrix (ECM) proteins is crucial for
      cell adhesion to titanium. Since GDP+ induced both inorganic adsorption and cell
      adhesion, we hypothesized that the inorganic adsorption in a culture medium might
      affect the adsorption of the ECM proteins. In this study, ECM proteins adsorbed
      on titanium with and without GDP were examined by x-ray photoelectron
      spectroscopy. After 1 hr of incubation, increasing sodium adsorption on GDP+
      specimens induced adsorption of ECM proteins as shown by NH(+) and COO(-) signals
      without calcium adsorption. In contrast, since no specific adsorption of sodium
      on GDP-specimens was detected, GDP-did not contribute to the adsorption of ECM
      proteins. Thus, promotion of sodium adsorption of GDP+ was effective, at least in
      the initial ECM protein adsorption on a titanium surface.

PMID- 15972600
TI  - Functional analysis of MRG-1: the ortholog of human MRG15 in Caenorhabditis
      elegans.
AB  - Mortality Factor on Chromosome 4 (MORF4) induces senescence in several immortal
      human cell lines. MORF-related gene on chromosome 15 (MRG15), another expressed
      family member, is highly conserved and expressed in yeast to humans. To determine
      the biological functions of human MRG15 (hMRG15) we used RNA-mediated
      interference (RNAi) to silence mrg-1, the Caenorhabditis elegans ortholog, and
      its closest homolog Y37D8A.11. Expression of mrg-1 RNAi resulted in sterility,
      body wall defects, vulval protrusion, and posterior developmental defects in
      worms. We expressed mrg-1 under its own and the cytomegalovirus promoter in human
      cells. Both constructs were expressed, indicating that C. elegans promoter
      elements are functional in mammalian cells. Overexpression from the
      cytomegalovirus promoter eventually resulted in cell death, possibly due to
      competition with hMRG15 in endogenous nucleoprotein complexes. Recent data
      indicate a role for yeast and human MRG15 in transcriptional regulation via
      chromatin remodeling. Here we demonstrate the importance of mrg-1 in development
      and reproduction in C. elegans and discuss its potential to impact the aging
      process.

PMID- 15972601
TI  - Counting the calories: the role of specific nutrients in extension of life span
      by food restriction.
AB  - Reduction of food intake without malnourishment extends life span in many
      different organisms. The majority of work in this field has been performed in
      rodents where it has been shown that both restricting access to the entire diet
      and restricting individual dietary components can cause life-span extension.
      Thus, for insights into the mode of action of this intervention, it is of great
      interest to investigate the aspects of diet that are critical for life span
      extension. Further studies on the mechanisms of how food components modify life
      span are well suited to the model organism Drosophila melanogaster because of its
      short life span and ease of handling and containment. Therefore, we summarize
      practical aspects of implementing dietary restriction in this organism, as well
      as highlight the major advances already made. Delineation of the nutritional
      components that are critical for life-span extension will help to reveal the
      mechanisms by which it operates.

PMID- 15972602
TI  - An immune risk phenotype, cognitive impairment, and survival in very late life:
      impact of allostatic load in Swedish octogenarian and nonagenarian humans.
AB  - In the previous OCTO longitudinal study, we identified an immune risk phenotype
      (IRP) of high CD8 and low CD4 numbers and poor proliferative response. We also
      demonstrated that cognitive impairment constitutes a major predictor of
      nonsurvival. In the present NONA longitudinal study, we simultaneously examine in
      a model of allostatic load IRP and compromised cognition in 4-year survival in a
      population-based sample (n = 138, 86-94 years). Immune system measurements
      consisted of determinations of T-cell subsets, plasma interleukin 6 and
      cytomegalovirus and Epstein-Barr virus serology. Interleukin 2 responsiveness to
      concanavalin A, using data from the previous OCTO (octogenarians) immune study,
      hereafter OCTO immune, was also examined. Cognitive status was rated using a
      battery of neuropsychological tests. Logistic regression indicated that the IRP
      and cognitive impairment together predicted 58% of observed deaths. IRP was
      associated with late differentiated CD8+CD28-CD27- cells (p < .001), decreased
      interleukin 2 responsiveness (p < .05) and persistent viral infection (p < .01).
      Cognitive impairment was associated with increased plasma interleukin 6 (p <
      .001). IRP individuals with cognitive impairment were all deceased at the follow
      up, indicating an allostatic overload.

PMID- 15972603
TI  - Predictors of transitions in vitality: the italian longitudinal study on aging.
AB  - It is widely acknowledged that there is a strong need to identify which
      modifiable risk factors predict healthy aging to use this information as the
      scientific basis for systematic interventions. Data from a 4-year longitudinal
      study on aging among 5632 older Italians were used. The definition of vitality
      was based on both cognitive and physical status, and the envisaged transitions
      were: positive or nonpositive stable, positive or negative transition, lost, and
      deceased. Predictors associated with different vitality trajectories were
      investigated by multinomial logistic analysis with a six-level outcome. Age and
      educational level were predictors of being "positive stable," whereas the other
      factors behaved differently according to comparison group. For example, being
      overweight is a common predictor except when compared to the deceased group, as
      is depressive symptomatology except when compared to the "positive transition"
      group. Interventions are warranted to reduce social inequalities, promote
      adequate body weight, and prevent and treat depressive symptoms.

PMID- 15972605
TI  - Should the NCEP III guidelines be changed in elderly and younger persons at high
      risk for cardiovascular events?

PMID- 15972604
TI  - Disentangling the genetic determinants of human aging: biological age as an
      alternative to the use of survival measures.
AB  - The choice of a phenotype is critical for the study of a complex genetically
      regulated process, such as aging. To date, most of the twin and family studies
      have focused on broad survival measures, primarily age at death or exceptional
      longevity. However, on the basis of recent studies of twins and families,
      biological age has also been shown to have a strong genetic component, with
      heritability estimates ranging from 27% to 57%. The aim of this review is
      twofold: first, to summarize growing consensus on reliable methods of biological
      age assessment, and second, to demonstrate validity of this phenotype for
      research in the genetics of aging in humans.

PMID- 15972606
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" What do we do for the very old?

PMID- 15972607
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" Preventive gerontology: edging
      ever closer to the "barrier to immortality".

PMID- 15972608
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" Hyperlipidemia in seniors: too
      much, too little, too late?

PMID- 15972609
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" Aim low.

PMID- 15972610
TI  - Aronow's "Should the NCEP III guidelines be changed in elderly and younger
      persons at high risk for cardiovascular events?" Cholesterol and the aged: ...and
      the beat goes on.

PMID- 15972611
TI  - Patients, mean age 70 years, with automatic implantable cardioverter
      defibrillators treated with dual-chamber rate responsive pacing (DDDR-70) have a
      higher mortality than patients with backup ventricular pacing (VVI-40) at 3.7
      year follow-up.
AB  - BACKGROUND: One study showed in 506 patients with automatic implantable
      cardioverter-defibrillators (AICDs) that the mortality at 1-year follow-up was
      6.5% with ventricular backup pacing at 40/minute (VVI-40) versus 10.1% in
      patients with dual-chamber rate responsive pacing at 70/minute (DDDR-70).
      METHODS: We performed a retrospective study to determine all-cause mortality in
      all patients at a university hospital who had AICDs without indications for
      antibradycardia pacing. Of 535 patients, mean age 70 +/- 12 years, 271 patients
      had backup ventricular pacing with a VVI-40, and 264 patients had dual-chamber
      rate responsive pacing with a DDDR-70. RESULTS: At 3.7-year mean follow-up, all
      cause mortality was 19% (50 of 264 patients) in patients with DDDR-70 pacing
      versus 11% (29 of 271 patients) with VVI-40 pacing (p < .01). CONCLUSION: Because
      of the increased mortality, increased cost, and complexity for dual-chamber rate
      responsive pacing in patients with AICDs, concomitant DDDR pacing at a rate of
      70/minute in patients without an indication for antibradycardia pacing is not
      warranted.

PMID- 15972612
TI  - Inpatient telemetry does not need to be used in the management of older patients
      hospitalized with chest pain at low risk for in-hospital coronary events and
      mortality.
AB  - BACKGROUND: Little is known about patients admitted with chest pain to inpatient
      telemetry units directly from an emergency department. METHODS: We analyzed data
      from 105 consecutive patients who presented with chest pain to an emergency
      department and who were hospitalized in an inpatient telemetry unit but who were
      at low risk for a coronary event. RESULTS: Telemetry yielded no information which
      was used to manage any patient. None of the 105 patients (0%) developed a
      myocardial infarction or died during hospitalization. At 4.8-year follow-up, 8 of
      105 patients (8%) died. Significant risk factors for long-term mortality were age
      (p < .001), prior coronary artery disease (p < .05), and diabetes (p < .02).
      CONCLUSIONS: Inpatient telemetry was of no value in predicting short-term
      coronary events or mortality or long-term mortality in low-risk patients
      hospitalized with chest pain.

PMID- 15972613
TI  - Arterial pulse wave velocity as a marker of poor cognitive function in an elderly
      community-dwelling population.
AB  - BACKGROUND: Knowledge about potentially modifiable risk factors for cognitive
      decline is limited at this time. The aim of this study was to determine the cross
      sectional relationship between a low level of cognitive function and brachial
      ankle pulse wave velocity (baPWV) in a community-dwelling elderly population.
      METHODS: The study population included 352 community-dwelling Japanese persons
      ages 70 years and older who participated in a comprehensive health examination in
      April 2003. None had any history of cardiovascular disease. In addition to
      conventional medical examinations such as blood pressure and routine blood
      analyses, cognitive function was tested using the Mini-Mental State Examination
      (MMSE), and baPWV was determined using a recently developed noninvasive and
      automatic arterial waveform analyzer (AT-Form). This measure, with well
      established validity and reproducibility, reflects both central and peripheral
      arterial flow. A multivariate logistic regression model tested the possible
      association between poor cognitive function (an MMSE score < 24) and baPWV.
      RESULTS: Poor cognitive function was independently associated with the middle
      tertile of baPWV (odds ratio [OR] = 9.66, 95% confidence interval [CI] = 1.15 to
      80.93), age (1-year increment; OR = 1.12, 95% CI = 1.04 to 1.22), and the highest
      tertile of pulse pressure (OR = 4.70, 95% CI = 1.08 to 20.48) even after
      multivariate adjustment of data for the effects of age, educational level, and
      hemodynamic and metabolic antecedents of atherosclerosis. CONCLUSIONS: A high
      baPWV may be a potent risk factor for poor cognitive function in an elderly
      community-dwelling population, and this effect is independent of another marker
      of arterial stiffness: pulse pressure.

PMID- 15972614
TI  - Dietary variety predicts low body mass index and inadequate macronutrient and
      micronutrient intakes in community-dwelling older adults.
AB  - BACKGROUND: Low body mass index (BMI) and micronutrient deficiencies are
      associated with increased morbidity and mortality rates in old age. Whether
      adverse patterns of dietary variety predict both low BMI and low micronutrient
      intakes in older adults was investigated. METHODS: A cross-sectional analysis of
      national survey data was conducted in 1174 healthy adult men and women (ages 21
      to 90 years) who provided physiologically plausible dietary data in the 1994-1996
      Continuing Survey of Food Intakes by Individuals. Measurements included reported
      energy intake, protein intake (percentage meeting Recommended Dietary Allowance),
      micronutrient intakes (percentage meeting Estimated Average Requirements for 14
      micronutrients), and BMI. RESULTS: Adults who were 61 years or older consumed a
      greater total variety of foods, chose foods from a wider range of food groups,
      had a greater variety of micronutrient-dense foods and energy-weak foods, and had
      a lower variety of micronutrient-weak foods compared with adults ages 21 to 60
      years (p < .05 to.001). However, older adults with low BMIs (< 22 kg/m2) consumed
      a lower variety of energy-dense foods compared with older adults with higher BMIs
      (p < .05). The variety of energy-dense foods predicted both energy intake and BMI
      at all ages in multiple regression models controlling for confounding variables
      (R2 = .124 for energy, R2 = .574 for BMI, p < .001). A higher percentage of older
      persons had inadequate micronutrient intakes compared with younger persons (p <
      .05), especially vitamin E, calcium, and magnesium, but consumption of a
      particularly wide variety of micronutrient-rich foods helped counterbalance these
      trends (p < .05). Older adults who had a low BMI and consumed a low variety of
      micronutrient-dense foods were particularly at nutritional risk, with only 65.4%
      consuming the Recommended Dietary Allowance for protein and none meeting the
      Estimated Average Requirements for all 14 micronutrients. CONCLUSIONS: In
      contrast to previous suggestions that older persons consume a monotonous diet,
      this study showed that adults who were 61 years or older consumed a greater total
      food variety, and a greater variety of micronutrient-dense and energy-weak foods,
      compared with adults who were 60 years or younger. Although consumption of a low
      variety of energy-dense foods may contribute to reduced energy intake and body
      weight at any age, the variety of micronutrient-dense foods consumed needs to
      increase in old age to prevent micronutrient deficiencies. These findings suggest
      that all adults need advice on the changing needs for dietary variety with aging
      to maintain health, and that older persons with low BMI are particularly
      vulnerable to dietary shortfalls.

PMID- 15972615
TI  - Psychotropic medications and risk for falls among community-dwelling frail older
      people: an observational study.
AB  - BACKGROUND: Injuries due to falls are one of the most important public health
      concerns for all ages, but especially for frail elderly people. Although a small
      number of falls have a single cause, the majority have many different causes
      resulting from the interactions between intrinsic or extrinsic risk factors.
      METHODS: We conducted an observational study on data from a large population of
      community-dwelling elderly people to tests the hypothesis that the current use of
      different classes of psychotropic medications, including antipsychotic agents,
      benzodiazepines, nonbenzodiazepine sedative-hypnotics, and antidepressants,
      increases the risk for falls. We analyzed data from a large collaborative
      observational study group, the Italian Silver Network Home Care project, that
      collected data on patients admitted to home care programs (n = 2854). RESULTS:
      After adjusting for all potential confounders, users of any psychotropic drugs
      had an increased risk of fall of nearly 47% (adjusted odds ratio [OR], 1.47; 95%
      confidence interval [CI], 1.24-1.74). Similarly, compared with nonusers, users of
      atypical antipsychotic drugs also had an increased risk of falling at least once
      (OR, 1.45; 95% CI, 1.00-2.11). Among benzodiazepine users, patients taking agents
      with long elimination half-life (OR, 1.45; 95% CI, 1.00-2.19) and patients taking
      benzodiazepines with short elimination half-life (OR, 1.32; 95% CI, 1.02-1.72)
      had an increased risk of falls. Patients taking antidepressants did not show a
      higher risk of falling compared to nonusers (OR, 0.92; 95% CI, 0.83-1.41).
      CONCLUSIONS: Our data suggest that, among psychotropic medications, antipsychotic
      agents and benzodiazepines are associated with an increased risk of falls. Our
      findings do not support the hypothesis that preferential prescribing of short
      acting benzodiazepines instead of long-acting agents or atypical antipsychotic
      medications instead of typical agents will substantially decrease fall risk
      associated with the use of these classes of drugs.

PMID- 15972616
TI  - Effect of age on characteristics of forward and backward gait at preferred and
      accelerated walking speed.
AB  - BACKGROUND: Backward walking is used increasingly in rehabilitation programs to
      promote balance, strength, and aerobic conditioning. This study examines the
      effect of movement direction on the temporal-spatial gait characteristics of old
      versus young adults when progressing at a comfortable pace and as fast as
      possible. METHODS: Participants included 40 old (mean age 77.7, standard
      deviation +/- 6.2) and 30 young volunteers (mean age 24.0, standard deviation +/-
      2.3), who were independent walkers. Using a computer-based walkway system,
      participants were requested to walk forward and backward at a normal pace and as
      fast as possible. Analyses of variance and Tukey-Kramer tests were conducted to
      determine effects of age, movement direction, and acceleration of gait speed on
      various gait parameters. RESULTS: Forward and backward walking of elderly persons
      is generally characterized by a lower velocity, cadence, stride length, and swing
      phase, accompanied by an increase in the double-support phase. Reversing from
      forward to backward walking presents a similar pattern in both age groups, with a
      decrease in gait velocity, stride length, and swing phase, an increase in the
      double-support phase, and no change in cadence. However, the decrease in stride
      length is significantly greater among elderly persons. In young persons, higher
      gait velocities are achieved by concurrent increases in stride length and
      cadence, regardless of movement direction. Ability of older persons to increase
      backward ambulation is limited and relies solely on increasing cadence.
      CONCLUSIONS: Elderly persons demonstrate difficulties in walking backward, with
      stride length particularly affected. These difficulties must be considered when
      using backward ambulation for rehabilitation of elderly persons.

PMID- 15972617
TI  - Hyperkyphotic posture and poor physical functional ability in older community
      dwelling men and women: the Rancho Bernardo study.
AB  - BACKGROUND: Physical functional decline is often the determining factor that
      leads to loss of independence in older persons. Identifying risk factors for
      physical disability may lead to interventions that may prevent or delay the onset
      of functional decline. Our study objective was to determine the association
      between hyperkyphotic posture and physical functional limitations. METHODS:
      Participants were 1578 older men and women from the Rancho Bernardo Study who had
      kyphotic posture measured as the distance from the occiput to table (units = 1.7
      cm blocks, placed under the participant's head when lying supine on a radiology
      table). Self-reported difficulty in bending, walking, and climbing was assessed
      by standard questionnaires. Physical performance was assessed by measuring grip
      strength and ability to rise from a chair without the use of the arms. RESULTS:
      Men were more likely to be hyperkyphotic than were women (p <.0001). In multiply
      adjusted comparisons, there was a graded stepwise increase in difficulty in
      bending, walking and climbing, measured grip strength, and ability to rise from a
      chair. For example, the odds ratio (OR) of having to use the arms to stand up
      from a chair increased from 1.6 (95% confidence interval [CI]: 0.9-3.0) for
      individuals defined as hyperkyphotic by 1 block to 2.9 (95% CI: 1.7-5.1) for
      individuals defined as hyperkyphotic by 2 blocks to 3.7 (95% CI: 2.1-6.3) for
      individuals defined as hyperkyphotic by > or = 3 blocks compared to those who
      were not hyperkyphotic (p for trend < .0001). CONCLUSIONS: Older persons with
      hyperkyphotic posture are more likely to have physical functional difficulties.

PMID- 15972618
TI  - Optimal load for increasing muscle power during explosive resistance training in
      older adults.
AB  - BACKGROUND: Muscle power (force x velocity) recedes at a faster rate than
      strength with age and may also be a stronger predictor of fall risk and
      functional decline. The optimal training paradigm for improving muscle power in
      older adults is not known, although some literature suggests high velocity, low
      load training is optimal in young adults. METHODS: One hundred twelve healthy
      older adults (69 +/- 6 years) were randomly assigned to either explosive
      resistance training at 20% (G20), 50% (G50), or 80% (G80) one repetition maximum
      (1RM) for 8-12 weeks or to a nontraining control group (CON). Participants
      trained twice per week (five exercises; three sets of eight rapidly concentric
      and slow eccentric repetitions) using pneumatic resistance machines. Repeated
      measures analysis of variance and covariance (ANOVA and ANCOVA) were used to
      determine the effects of training. RESULTS: Average peak power increased
      significantly and similarly in G80 (14 +/- 8%), G50 (15 +/- 9%), and G20 (14 +/-
      6%) compared to CON (3 +/- 6%) (p < .0001). By contrast, a positive dose-response
      relationship with training intensity was observed for relative changes in average
      strength (r = .40, p = .0009) and endurance (r = .43, p = .0005). Average
      strength increased in G80 (20 +/- 7%), G50 (16 +/- 7%), and G20 (13 +/- 7%)
      compared to CON (4 +/- 4%) (p < .0001). Average muscle endurance increased in G80
      (185 +/- 126%, p < .0001), G50 (103 +/- 75%, p = .0004), and G20 (82 +/- 57%, p =
      .0078) compared to CON (28 +/- 29%). CONCLUSION: Peak muscle power may be
      improved similarly using light, moderate, or heavy resistances, whereas there is
      a dose-response relationship between training intensity and muscle strength and
      endurance changes. Therefore, using heavy loads during explosive resistance
      training may be the most effective strategy to achieve simultaneous improvements
      in muscle strength, power, and endurance in older adults.

PMID- 15972619
TI  - The effect of nandrolone decanoate on bone mineral density, muscle mass, and
      hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized,
      placebo-controlled clinical trial.
AB  - METHODS: In a randomized, double-blind, placebo-controlled clinical trial, we
      evaluated the effect of a 2-year treatment with nandrolone decanoate (ND) on bone
      mineral density (BMD) of lumbar spine, femoral neck, and trochanter and on
      vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five
      osteoporotic women older than 70 years were studied. Thirty-two patients received
      injections of 50 mg ND, and 33 received placebos every 3 weeks. All patients
      received 500 mg calcium tablets daily. RESULTS: Compared to baseline, ND
      increased the BMD of the lumbar spine (3.4% +/- 6.0 and 3.7% +/- 7.4; p < .05)
      and femoral neck (4.1% +/- 7.3 and 4.7% +/- 8.0; p < .05) after 1 and 2 years,
      respectively. The BMD of trochanter increased significantly only after the first
      year (4.8% +/- 9.3, p < .05). Compared to the placebo group, the ND group
      presented with significantly increased BMD of the trochanter and neck. ND
      significantly reduced incidence of new vertebral fractures (21% vs 43% in the
      placebo group; p < .05). ND showed a significant statistical increase in lean
      body mass after the first (6.2% +/- 5.8; p < .01) and second years (11.9% +/-
      29.2; p < .01). In addition, a 2-year treatment with ND significantly increased
      hemoglobin levels compared to baseline (14.3%; p < .01) and placebo (p < .01).
      CONCLUSIONS: ND increased BMD, hemoglobin levels, and muscle mass, and reduced
      the vertebral fracture rate of elderly osteoporotic women.

PMID- 15972620
TI  - Use of proxy respondents and accuracy of minimum data set assessments of
      activities of daily living.
AB  - BACKGROUND: Although the Minimum Data Set (MDS) presents a wide range of
      opportunities for policy makers and practitioners interested in outcomes of
      nursing home care for frail elderly persons, researchers have debated the
      validity and reliability of measurements in the MDS from the outset. To
      investigate this issue, the authors studied the accuracy of functional
      assessments by comparing the MDS and interview data collected in two evaluation
      studies. METHODS: Activities of daily living (ADL) assessment data from 3385
      nursing home residents were collected from interviews with nursing home residents
      (n = 1200), family members (n = 1070), and nursing home staff (n = 1115). The MDS
      data for these nursing home residents were obtained and matched with the
      interview data. The agreement in ADL assessments between interview data and the
      MDS was assessed using Kappa statistics and multinomial logit regression for each
      of the three data sources. RESULTS: The agreement on ADL assessments between MDS
      and interview data was low to moderate (Kappa = 0.25 to 0.52), regardless of the
      sources of data. Interview data from staff and family proxies agreed to a greater
      degree with the MDS than did data collected from nursing home residents. The MDS
      reported fewer ADL difficulties than did staff proxies and more ADL difficulties
      than did nursing home residents. These findings held even after adjustment for
      other confounding factors using multinomial logit regression. CONCLUSIONS: The
      substantial discrepancy between MDS and interview data can be attributed to both
      bias and error. The ADL assessments based on residents' and family or staff
      reports differ, but the size of these differences depends on the proxy type and
      the method of data collection.

PMID- 15972621
TI  - Early event-related potential changes during working memory activation predict
      rapid decline in mild cognitive impairment.
AB  - BACKGROUND: The conversion of mild cognitive impairment (MCI) to Alzheimer's
      disease is associated with substantial compromise of neocortical circuits
      subserving rapid cognitive functions such as working memory. Event-related
      potential (ERP) analysis is a powerful tool to identify early impairment of these
      circuits, yet research for an electrophysiological marker of cognitive
      deterioration in MCI is scarce. Using a "2-back" activation paradigm, we recently
      described an electrophysiological correlate of working memory activation
      (positive-negative working memory [PN(wm)] component) over parietal electrodes.
      METHODS: Ours was a longitudinal study of 24 MCI patients with ERP analysis at
      inclusion and neuropsychological follow-up after 1 year. We used ERP waveform
      subtraction analysis between the n-back and control tasks. Analysis of variance
      (ANOVA) was used to compare electroencephalograph latencies between progressive
      MCI (PMCI) and stable MCI (SMCI), and univariate regression was used to assess
      the relationship between neuropsychological measures at baseline and clinical
      outcome. RESULTS: Thirteen (54%) MCI patients showed PMCI, and 11 (46%) remained
      stable (SMCI). In SMCI, a PN(wm) component with significantly larger density
      compared to baseline was identified when subtracting the detection task for both
      the 1- and 2-back tasks. In contrast, in PMCI, the PN(wm) component was absent in
      both 1-back and 2-back conditions. Neuropsychological variables and n-back test
      performance at inclusion did not predict cognitive deterioration 1 year later.
      CONCLUSIONS: In conjunction with recent functional imaging data, the present
      results support the notion of an early dysfunction of neural generators within
      the parietal cortex in MCI. They also reveal that the absence of the PN(wm)
      component may provide an easily applicable qualitative predictive marker of rapid
      cognitive deterioration in MCI.

PMID- 15972622
TI  - A nonspeech investigation of tongue function in Parkinson's disease.
AB  - BACKGROUND: Nonspeech investigations of tongue function in persons with
      Parkinson's disease (PD) have generally reported impaired tongue strength,
      endurance, and fine force control. However, these investigations did not
      specifically evaluate the relative contribution of age effects to the deficits in
      tongue function observed. Furthermore, the relationship between these nonspeech
      measures of tongue function and the speech disorder present in PD remains
      equivocal. Therefore, the current study investigated the strength, rate of
      repetitive movement, fine force control, and endurance of the tongue in three
      groups of participants. METHODS: Participants in the study included 14 older
      adults with PD and imprecise consonant articulation, 11 neurologically healthy
      older adults, and 15 neurologically healthy young adults. All participants were
      assessed using a comprehensive nonspeech assessment battery of tongue function.
      RESULTS: The results of the investigation revealed similar levels of tongue
      strength, rate of repetitive movement, and endurance between the persons with PD
      and the older control participants. Significant age effects were noted, with both
      groups demonstrating significantly reduced functioning on those measures when
      compared to young control participants. However, the three participant groups had
      similar levels of fine force control. No relationship was found between the
      nonspeech measures of tongue function employed and the severity of consonant
      imprecision. CONCLUSION: The nonspeech measures used failed to provide useful
      diagnostic information regarding the physiologic basis of perceived articulatory
      dysfunction in the persons with PD who were examined.

PMID- 15972623
TI  - The world of TH1/TH2 subsets: first proof.

PMID- 15972624
TI  - Two types of murine helper T cell clone. I. Definition according to profiles of
      lymphokine activities and secreted proteins. 1986.

PMID- 15972625
TI  - Modulation of dendritic cell maturation and function by B lymphocytes.
AB  - Investigating the signals that regulate the function of dendritic cells (DC), the
      sentinels of the immune system, is critical to understanding the role of DC in
      the regulation of immune responses. Accumulating lines of evidence indicate that
      in addition to innate stimuli and T cell-derived signals, B lymphocytes exert a
      profound regulatory effect in vitro and in vivo on the Ag-presenting function of
      DC. The identification of B cells as a cellular source of cytokines, chemokines,
      and autoantibodies that are critically involved in the process of maturation,
      migration, and function of DC provides a rationale for immunotherapeutic
      intervention of autoimmune and inflammatory conditions by targeting B cells.
      Conversely, efficient cross-presentation of Ags by DC pulsed with immune
      complexes provides an alternative approach in the immunotherapy of cancer and
      infectious diseases.

PMID- 15972626
TI  - The link between lymphocyte deficiency and autoimmunity: roles of endogenous T
      and B lymphocytes in tolerance.
AB  - We demonstrate that transfer of OVA-specific DO11 CD4(+) T cells into mice that
      lack T and B cells and produce secreted OVA as an endogenous self-protein results
      in a severe systemic autoimmune reaction with skin inflammation, wasting, and
      death. The transferred DO11 T cells undergo massive expansion and produce IL-2
      and IFN-gamma abundantly. Transfer of DO11 cells into OVA-expressing animals in
      which T cells are absent but B cells are present, leads to mild disease with no
      death. In this situation, the DO11 cells undergo similar expansion but show poor
      Th1 differentiation. This regulatory effect of B cells correlates with profound
      TCR down-regulation. If T cells are present, the DO11 cells fail to expand
      independent of B cells. These results suggest that both endogenous T and B
      lymphocytes control T cell tolerance induction and pathogenicity, but at
      different stages of an anti-self response. Although endogenous T cells prevent
      expansion and maintain homeostasis, endogenous B cells limit subsequent effector
      responses of autoreactive CD4(+) T cells.

PMID- 15972627
TI  - B-1 cells are deficient in Lck: defective B cell receptor signal transduction in
      B-1 cells occurs in the absence of elevated Lck expression.
AB  - B-1 cells constitute a unique B cell subset that is primarily responsible for
      producing nonimmune Ig. This natural Ig acts as a principal line of defense
      against infection. A key feature of B-1 cells is the failure of BCR-triggered
      signal transduction. Recently, defective BCR signaling in B-1 cells has been
      attributed to elevated expression of the canonical T cell src kinase, Lck. In the
      present study, we re-examined Lck expression in normal B-1 cells. We found that B
      1 cells expressed less Lck at both the protein and RNA levels than did B-2 cells.
      The same B-1 cells manifested defective BCR-mediated induction of IKKbeta
      phosphorylation, IkappaBalpha degradation, and intracellular Ca(2+) mobilization.
      Thus, the failure of BCR signaling in B-1 cells does not relate to subset
      specific elevation of Lck.

PMID- 15972628
TI  - In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly
      susceptible to CD95 ligand- but not to TCR-mediated cell death.
AB  - CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) suppress T cell function and
      protect rodents from autoimmune disease. Regulation of T(reg) during an immune
      response is of major importance. Enhanced survival of T(reg) is beneficial in
      autoimmune disease, whereas increased depletion by apoptosis is advantageous in
      cancer. We show here that freshly isolated FACS-sorted T(reg) are highly
      sensitive toward CD95-mediated apoptosis, whereas other T cell populations are
      resistant to CD95-induced apoptosis shortly after isolation. In contrast, TCR
      restimulation of T(reg) in vitro revealed a reduced sensitivity toward activation
      induced cell death compared with CD4(+)CD25(-) T cells. Thus, the apoptosis
      phenotype of T(reg) is unique in comparison to other T cells, and this might be
      further explored for novel therapeutic modulations of T(reg).

PMID- 15972629
TI  - Low-affinity, Smith antigen-specific B cells are tolerized by dendritic cells and
      macrophages.
AB  - Polyclonal B cell activation promotes immunity without the loss of tolerance. Our
      data show that during activation of the innate immune system, B cell tolerance to
      Smith Ag Sm is maintained by dendritic cells (DCs) and macrophages (MPhi). TLR4
      activated myeloid DCs and MPhi, but not plasmacytoid or lymphoid DCs, repressed
      autoreactive B cells through the secretion of soluble mediators, including IL-6.
      Although IL-6 promotes plasma cell differentiation of B cells acutely stimulated
      by Ag, we show that it repressed cells that were chronically exposed to self-Ag.
      This mechanism of tolerance was not limited to Smith Ag-specific B cells as hen
      egg lysozyme- and p-azophenylarsonate-specific B cells were similarly affected.
      Our data define a tolerogenic role for MPhi and DCs in regulating autoreactive B
      cells during activation of the innate immune system.

PMID- 15972630
TI  - Impact of cutaneous IL-10 on resident epidermal Langerhans' cells and the
      development of polarized immune responses.
AB  - Prolonged topical exposure of BALB/c mice to chemical contact and respiratory
      allergens stimulates, respectively, preferential Th1- and Th2-type responses with
      respect to serum Ab isotype and cytokine secretion phenotypes displayed by
      draining lymph node cells. We now report that differential cytokine secretion
      patterns are induced rapidly in the skin following first exposure to the contact
      allergen 2,4-dinitrochlorobenzene (DNCB) and the respiratory sensitizer
      trimellitic anhydride (TMA). TMA induced early expression of IL-10, a cytokine
      implicated in the negative regulation of Langerhans cell (LC) migration, whereas
      exposure to DNCB resulted in production of the proinflammatory cytokine IL-1beta.
      Associated with this, TMA provoked LC migration with delayed kinetics compared
      with DNCB, and local neutralization of IL-10 caused enhanced LC mobilization in
      response to TMA with concomitant up-regulation of cutaneous IL-1beta. We
      hypothesize that these differential epidermal cytokine profiles contribute to the
      polarization of immune responses to chemical allergens via effects on the
      phenotype of activated dendritic cells arriving in the draining lymph node. Thus,
      TMA-exposed dendritic cells that have been conditioned in vivo with IL-10 (a
      potent inhibitor of the type 1-polarizing cytokine IL-12) are effective APCs for
      the development of a Th2-type response.

PMID- 15972631
TI  - Roles of deletion and regulation in creating mixed chimerism and allograft
      tolerance using a nonlymphoablative irradiation-free protocol.
AB  - The induction of mixed chimerism (MC) is a powerful and effective means to
      achieve transplantation tolerance in rodent models. Host conditioning with
      irradiation or cytotoxic drugs has been used in many protocols for chimeric
      induction across allogeneic barriers. The deletion of alloreactive T cell clones
      has been described as the main mechanism responsible for the induction of a
      stable MC. In this study, we demonstrate that a stable MC and skin allograft
      tolerance can be established across MHC barriers by a noncytotoxic, irradiation
      free approach using costimulation blockade plus rapamycin treatment. By using an
      adoptive transfer model of skin allograft and using specific Vbeta TCR probes, we
      demonstrated that deletion of donor-reactive cytopathic T cell clones is indeed
      profound in tolerant hosts. Nonetheless, the challenge of tolerant mixed chimeras
      with 5 million mononuclear leukocytes (MNL) from naive syngeneic mice was neither
      able to abolish the stable MC nor to trigger skin allograft rejection, a hallmark
      of peripheral, not central tolerance. Furthermore, in an adoptive transfer model,
      MNLs harvested from tolerant hosts significantly inhibited the capacity of naive
      MNLs to reject same donor, but not third-party, skin allografts. Moreover, when
      we transplanted skin allografts from stable tolerant chimeras onto syngeneic
      immune-incompetent mice, graft-infiltrating T cells migrated from the graft site,
      expanded in the new host, and protected allografts from acute rejection by naive
      syngeneic MNLs. In this model, both deletional and immunoregulatory mechanisms
      are active during the induction and/or maintenance of allograft tolerance through
      creation of MC using a potentially clinically applicable regimen.

PMID- 15972632
TI  - Human first-trimester trophoblast cells recruit CD56brightCD16- NK cells into
      decidua by way of expressing and secreting of CXCL12/stromal cell-derived factor
      1.
AB  - More than 70% of decidual lymphocytes are NK cells characterized by
      CD56(bright)CD16(-) phenotype, but the mechanisms by which these NK cells are
      recruited in the decidua are still almost unrevealed. In this study, we first
      analyzed the transcription of 18 chemokine receptors in the first-trimester
      decidual CD56(bright)CD16(-) NK cells. Among these receptors, CXCR4 and CXCR3
      were found highly transcribed, and the expression of CXCR4 was verified in most
      of the decidual CD56(bright)CD16(-) NK cells by flow cytometry. The first
      trimester human trophoblasts were found expressing CXCL12/stromal cell-derived
      factor 1, the specific ligand of CXCR4, by way of in situ hybridization and
      immunohistochemistry. The primary cultured trophoblast cells were also found to
      secrete stromal cell-derived factor 1alpha spontaneously, and its concentration
      was 384.6 +/- 90.7 pg/ml after the trophoblast cells had been cultured for 60 h.
      All of the ligands for CXCR3 were below the minimal detectable concentration when
      trophoblast cells were cultured for up to 48 h. Both recombinant human SDF-1alpha
      and supernatants of the cultured trophoblast cells exhibited chemotactic activity
      on decidual CD56(bright)CD16(-) NK cells. Our findings suggest that human first
      trimester trophoblast cells produce CXCL12, which in turn chemoattracts decidual
      CD56(bright)CD16(-) NK cells. This activity could contribute to the recruitment
      mechanism of decidual lymphocytes, especially CD56(bright)CD16(-) NK cells, in
      decidua, and may be used at a local level to modulate the immune milieu at the
      materno-fetal interface.

PMID- 15972633
TI  - Autoimmune CD4+ T cell memory: lifelong persistence of encephalitogenic T cell
      clones in healthy immune repertoires.
AB  - We embedded green fluorescent CD4(+) T cells specific for myelin basic protein
      (MBP) (T(MBP-GFP) cells) in the immune system of syngeneic neonatal rats. These
      cells persisted in the animals for the entire observation period spanning >2
      years without affecting the health of the hosts. They maintained a memory
      phenotype with low levels of L-selectin and CD45RC, but high CD44. Although
      persisting in low numbers (0.01-0.1% of lymph node cells) they were sufficient to
      raise susceptibility toward clinical autoimmune disease. Immunization with MBP in
      IFA induced CNS inflammation and overt clinical disease in animals carrying
      neonatally transferred T(MBP-GFP) cells, but not in controls. The onset of the
      clinical disease coincided with mass infiltration of T(MBP-GFP) cells into the
      CNS. In the periphery, following the amplification phase a rapid contraction of
      the T cell population was observed. However, elevated numbers of fully reactive
      T(MBP-GFP) cells remained in the peripheral immune system after acute
      experimental autoimmune encephalomyelitis mediating reimmunization-induced
      disease relapses.

PMID- 15972634
TI  - A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor
      of human leukemic lymphocytes.
AB  - The P2X(7)R is an ATP-gated cation channel expressed in hemopoietic cells that
      participates in both cell proliferation and apoptosis. Expression and function of
      the P2X(7)R have been associated with the clinical course of patients affected by
      chronic lymphocytic leukemia (CLL). Functional variants causing loss-of-function
      of the P2X(7)R have been identified, namely, polymorphisms 1513A>C (E496A),
      1729T>A (I568N), and 946G>A (R307Q). Here we investigated other nonsynonymous
      polymorphisms located either in the extracellular portion of the receptor, such
      as the 489C>T (H155Y) variant, or in the long cytoplasmic tail of the receptor,
      such as the 1068G>A (A348T), 1096C>G (T357S), and 1405A>G (Q460R) variants.
      P2X(7)R function was monitored by measuring ATP-induced Ca(2+) influx in PBL of
      patients affected by CLL and in recombinant human embryonic kidney (HEK) 293
      cells stably transfected with each single P2X(7) allelic variant. Ca(2+) influx
      was markedly reduced in association with the 1513C allele, whereas variants
      located in the same intracellular domain, such as the 1068A, 1096G, or 1405G
      variants, were associated with a minor functional decrease. Significant Ca(2+)
      flux increase was observed in lymphocytes from CLL patients bearing the 489C/T
      and 489T/T genotypes in association with the 1513A/A genotype. Functional
      analysis in recombinant HEK293 cells expressing P2X(7)R confirmed an increased
      ATP-dependent activation of the P2X(7) 489T mutant with respect to the wild type
      receptor, as assessed by both by [Ca(2+)](i) influx and ethidium uptake
      experiments. These data identify the 489C>T as a gain-of-function polymorphism of
      the P2X(7)R.

PMID- 15972635
TI  - Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to aryl
      hydrocarbon receptor-dependent nuclear translocation of NF-kappaB and expression
      of Fas ligand in thymic stromal cells and consequent apoptosis in T cells.
AB  - We investigated the role of aryl hydrocarbon receptor (AhR) in the regulation of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced apoptosis in thymic T cells.
      AhR knockout (KO) mice were resistant to TCDD-induced thymic atrophy and
      apoptosis when compared with the AhR wild-type mice. TCDD triggered the
      expression of several apoptotic genes, including FasL in AhR wild-type but not
      AhRKO mice. TCDD-induced increase in FasL was seen only in thymic stromal but not
      thymic T cells. When TCDD-exposed stromal cells were mixed with untreated thymic
      T cells, increased apoptosis was detected in T cells that involved Fas-FasL
      interactions. Thus, apoptosis in T cells was not detected when TCDD-treated
      stromal cells from FasL-defective or AhRKO mice were mixed with wild-type T cells
      or when TCDD-exposed wild-type stromal cells were mixed with Fas-deficient T
      cells. TCDD treatment, in vivo and in vitro, led to colocalization and
      translocation of NF-kappaB subunits (p50, p65) to the nucleus in stromal but not
      T cells from AhR wild-type mice. NF-kappaB activation was not observed in stromal
      cells isolated from TCDD-treated AhRKO mice. Mutations in NF-kappaB-binding sites
      on the FasL promoter showed that TCDD regulates FasL promoter activity through NF
      kappaB. TCDD treatment in vivo caused activation of the death receptor and
      mitochondrial pathways of apoptosis. Cross-talk between the two pathways was not
      necessary for apoptosis inasmuch as TCDD-treated Bid KO mice showed thymic
      atrophy and increased apoptosis, similar to the wild-type mice. These findings
      demonstrate that AhR regulates FasL and NF-kappaB in stromal cells, which in turn
      plays a critical role in initiating apoptosis in thymic T cells.

PMID- 15972636
TI  - The influence of effector T cells and Fas ligand on lupus-associated B cells.
AB  - Circulating autoantibodies against dsDNA and chromatin are a characteristic of
      systemic lupus erythematosus in humans and many mouse models of this disease. B
      cells expressing these autoantibodies are normally regulated in nonautoimmune
      prone mice but are induced to secrete Abs following T cell help. Likewise, anti
      chromatin autoantibody production is T cell-dependent in Fas/Fas ligand (FasL)
      deficient (lpr/lpr or gld/gld) mice. In this study, we demonstrate that Th2 cells
      promote anti-chromatin B cell survival and autoantibody production in vivo. FasL
      influences the ability of Th2 cells to help B cells, as Th2-gld/gld cells support
      higher titers of anti-chromatin Abs than their FasL-sufficient counterparts and
      promote anti-chromatin B cell participation in germinal centers. Th1 cells induce
      anti-chromatin B cell germinal centers regardless of FasL status; however, their
      ability to stimulate anti-chromatin Ab production positively correlates with
      their level of IFN-gamma production. This distinction is lost if FasL-deficient T
      cells are used: Th1-gld/gld cells promote significant titers of anti-chromatin
      Abs regardless of IFN-gamma production levels. Thus, FasL from effector T cells
      plays an important role in determining the fate of anti-chromatin B cells.

PMID- 15972638
TI  - Disruption of CD40/CD40-ligand interactions in a retinal autoimmunity model
      results in protection without tolerance.
AB  - We examined the role of CD40/CD40L interactions on the development of
      experimental autoimmune uveoretinitis (EAU), a cell-mediated, Th1-driven
      autoimmune disease that serves as a model for autoimmune uveitis in humans. EAU
      susceptible B10.RIII mice immunized with the retinal autoantigen
      interphotoreceptor retinoid binding protein in CFA and treated with anti-CD40L Ab
      (MR1) had reduced incidence and severity of disease. Real-time PCR analysis
      revealed that the innate and adaptive responses of protected mice were reduced,
      without an obvious shift toward a Th2 cytokine profile. In contrast to some other
      reports, no evidence was found for regulatory cells in adoptive transfer
      experiments. To determine whether CD40L blockade resulted in long-term tolerance,
      mice protected by treatment with MR1 Ab were rechallenged for uveitis after
      circulating MR1 Ab levels dropped below the detection limit of ELISA. MR1-treated
      mice developed severe EAU and strong cellular responses to interphotoreceptor
      retinoid binding protein, comparable to those of control mice. These responses
      were higher than in mice that had not received the primary immunization
      concurrently with anti-CD40L treatment. We conclude that 1) CD40/CD40L
      interaction is required for EAU and its disruption prevents disease development;
      2) CD40L blockade inhibits the innate response to immunization and reduces
      priming, but does not result in immune deviation; and 3) protection is dependent
      on persistence of anti-CD40L Abs, and long-term tolerance is not induced.
      Furthermore, immunological memory develops under cover of CD40L blockade causing
      enhanced responses upon rechallenge. Taken together, our data suggest that
      ongoing CD40/CD40L blockade might be required to maintain a therapeutic effect
      against uveitis.

PMID- 15972637
TI  - Coimmunization with an optimized IL-15 plasmid results in enhanced function and
      longevity of CD8 T cells that are partially independent of CD4 T cell help.
AB  - DNA vaccines are a promising technology for the induction of Ag-specific immune
      responses, and much recent attention has gone into improving their immune
      potency. In this study we test the feasibility of delivering a plasmid encoding
      IL-15 as a DNA vaccine adjuvant for the induction of improved Ag-specific CD8(+)
      T cellular immune responses. Because native IL-15 is poorly expressed, we used
      PCR-based strategies to develop an optimized construct that expresses 80-fold
      higher than the native IL-15 construct. Using a DNA vaccination model, we
      determined that immunization with optimized IL-15 in combination with HIV-1gag
      DNA constructs resulted in a significant enhancement of Ag-specific CD8(+) T cell
      proliferation and IFN-gamma secretion, and strong induction of long-lived CD8(+)
      T cell responses. In an influenza DNA vaccine model, coimmunization with plasmid
      expressing influenza A PR8/34 hemagglutinin with the optimized IL-15 plasmid
      generated improved long term CD8(+) T cellular immunity and protected the mice
      against a lethal mucosal challenge with influenza virus. Because we observed that
      IL-15 appeared to mostly adjuvant CD8(+) T cell function, we show that in the
      partial, but not total, absence of CD4(+) T cell help, plasmid-delivered IL-15
      could restore CD8 secondary immune responses to an antigenic DNA plasmid,
      supporting the idea that the effects of IL-15 on CD8(+) T cell expansion require
      the presence of low levels of CD4 T cells. These data suggest a role for enhanced
      plasmid IL-15 as a candidate adjuvant for vaccine or immunotherapeutic studies.

PMID- 15972639
TI  - Homeostatic role of interferons conferred by inhibition of IL-1-mediated
      inflammation and tissue destruction.
AB  - In addition to their well known immune and proinflammatory activities, IFNs
      possess homeostatic functions that limit inflammation and tissue destruction in a
      variety of conditions such as arthritis, osteolysis, and multiple sclerosis. The
      mechanisms underlying the homeostatic actions of IFNs are not well understood. We
      report here that both type I and type II IFNs (IFN-alpha, IFN-beta, and IFN
      gamma, respectively) suppressed a broad range of proinflammatory and tissue
      destructive activities of IL-1, including induction of inflammatory mediators,
      production of matrix metalloproteinases, macrophage tissue invasion, and
      cartilage degradation. IFN-alpha attenuated IL-1-mediated cell recruitment in
      vivo. IFNs completely suppressed the activation of IL-1 signal transduction
      pathways in macrophages. The mechanism of IFN-mediated inhibition of IL-1 action
      and signaling was modulation of IL-1R expression, which was also observed in
      vivo. IFN-gamma-mediated down-regulation of IL-1R type I expression was dependent
      on Stat1, a transcription factor typically considered to be a key mediator of
      macrophage activation by IFNs. These results identify cellular and molecular
      mechanisms that contribute to the homeostatic role of IFNs in limiting
      inflammation and associated tissue destruction.

PMID- 15972640
TI  - Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice.
AB  - Although livers transplanted across MHC barriers in mice are normally accepted
      without recipient immune suppression, the underlying mechanisms remain to be
      clarified. To identify the cell type that contributes to induction of such a
      tolerance state, we established a mixed hepatic constituent cell-lymphocyte
      reaction (MHLR) assay. Irradiated C57BL/6 (B6) or BALB/c mouse hepatic
      constituent cells (HCs) and CFSE-labeled B6 splenocytes were cocultured. In
      allogeneic MHLR, whole HCs did not promote T cell proliferation. When liver
      sinusoidal endothelial cells (LSECs) were depleted from HC stimulators,
      allogeneic MHLR resulted in marked proliferation of reactive CD4(+) and CD8(+) T
      cells. To test the tolerizing capacity of the LSECs toward alloreactive T cells,
      B6 splenocytes that had transmigrated through monolayers of B6, BALB/c, or SJL/j
      LSECs were restimulated with irradiated BALB/c splenocytes. Nonresponsiveness of
      T cells that had transmigrated through allogeneic BALB/c LSECs and marked
      proliferation of T cells transmigrated through syngeneic B6 or third-party SJL/j
      LSECs were observed after the restimulation. Transmigration across the Fas ligand
      deficient BALB/c LSECs failed to render CD4(+) T cells tolerant. Thus, we
      demonstrate that Fas ligand expressed on naive LSECs can impart tolerogenic
      potential upon alloantigen recognition via the direct pathway. This presents a
      novel relevant mechanism of liver allograft tolerance. In conclusion, LSECs are
      capable of regulating a polyclonal population of T cells with direct
      allospecificity, and the Fas/Fas ligand pathway is involved in such LSEC-mediated
      T cell regulation.

PMID- 15972641
TI  - Independent trafficking of Ig-alpha/Ig-beta and mu-heavy chain is facilitated by
      dissociation of the B cell antigen receptor complex.
AB  - The BCR relays extracellular signals and internalizes Ag for processing and
      presentation. We have previously demonstrated that ligation of the BCR
      destabilizes Ig-alpha/Ig-beta (Ig-alphabeta) from mu-H chain (mum). In this study
      we report that receptor destabilization represents a physical separation of mum
      from Ig-alphabeta. Sucrose gradient fractionation localized Ig-alphabeta to G(M1)
      containing lipid microdomains in the absence of mum. Confocal and electron
      microscopy studies revealed the colocalization of unsheathed mum with clathrin
      coated vesicles. Furthermore, mum failed to associate with clathrin-coated
      vesicles when receptor destabilization was inhibited, suggesting that unsheathing
      of mum is required for clathrin-mediated endocytosis. In summary, we found that
      Ag stimulation physically separates Ig-alphabeta from mum, facilitating
      concomitant signal transduction and Ag delivery to the endocytic compartment.

PMID- 15972642
TI  - Acute lipopolysaccharide-mediated injury in neonatal white matter glia: role of
      TNF-alpha, IL-1beta, and calcium.
AB  - Bacterial infection is implicated in the selective CNS white matter injury
      associated with cerebral palsy, a common birth disorder. Exposure to the
      bacterial endotoxin LPS produced death of white matter glial cells in isolated
      neonatal rat optic nerve (RON) (a model white matter tract), over a 180-min time
      course. A delayed intracellular Ca(2+) concentration ([Ca(2+)](i)) rise preceded
      cell death and both events were prevented by removing extracellular Ca(2+). The
      cytokines TNF-alpha or IL-1beta, but not IL-6, mimicked the cytotoxic effect of
      LPS, whereas blocking either TNF-alpha with a neutralizing Ab or IL-1 with
      recombinant antagonist prevented LPS cytotoxicity. Ultrastructural examination
      showed wide-scale oligodendroglial cell death in LPS-treated rat optic nerves,
      with preservation of astrocytes and axons. Fluorescently conjugated LPS revealed
      LPS binding on microglia and astrocytes in neonatal white and gray matter.
      Astrocyte binding predominated, and was particularly intense around blood
      vessels. LPS can therefore bind directly to developing white matter astrocytes
      and microglia to evoke rapid cell death in neighboring oligodendroglia via a
      calcium- and cytokine-mediated pathway. In addition to direct toxicity, LPS
      increased the degree of acute cell death evoked by ischemia in a calcium
      dependent manner.

PMID- 15972643
TI  - Effects of increasing IL-7 availability on lymphocytes during and after
      lymphopenia-induced proliferation.
AB  - IL-7 is critically involved in regulating peripheral T cell homeostasis. To
      investigate the role of IL-7 on lymphopenia-induced proliferation of polyclonal
      lymphocytes, we have transferred CFSE-labeled cells into a novel T-lymphopenic,
      IL-7-transgenic mouse line. Results obtained indicate that T and B cells do not
      respond in the same way to IL-7-homeostatic signals. Overexpression of IL-7
      enhances proliferation of both CD4(+) and CD8(+) T cells but with distinctly
      temporal effects. Expansion of naturally arising CD4(+)-regulatory T cells was
      like that of conventional CD4(+) T cells. IL-7 had no effect on B cell
      proliferation. By immunohistology, transferred T cells homed to T cell areas of
      spleen lymphoid follicles. Increasing IL-7 availability enhanced T cell recovery
      by promoting cell proliferation and reducing apoptosis during early stages of
      lymphopenia-induced proliferation. Taken together, these results provide new
      insights into the pleiotropic effects of IL-7 on lymphopenia-induced T cell
      proliferation.

PMID- 15972644
TI  - Helicobacter pylori-induced IL-8 production by gastric epithelial cells up
      regulates CD74 expression.
AB  - CD74, or the class II MHC-associated invariant chain, is best known for the
      regulation of Ag presentation. However, recent studies have suggested other
      important roles for this protein in inflammation and cancer studies. We have
      shown that CD74 is expressed on the surface of gastric cells, and Helicobacter
      pylori can use this receptor as a point of attachment to gastric epithelial
      cells, which lead to IL-8 production. This study investigates the ability of H.
      pylori to up-regulate one of its receptors in vivo and with a variety of gastric
      epithelial cell lines during infection with H. pylori. CD74 expression was
      increased dramatically on gastric biopsies from H. pylori-positive patients and
      gastric cell lines exposed to the bacteria. Gastric cells exposed to H. pylori
      conditioned medium revealed that the host cell response was responsible for the
      up-regulation of CD74. IL-8 was found to up-regulate CD74 cell surface expression
      because blocking IL-8Rs or neutralizing IL-8 with Abs counteracted the increased
      expression of CD74 observed during infection with H. pylori. These studies
      demonstrate how H. pylori up-regulates one of its own receptors via an autocrine
      mechanism involving one of the products induced from host cells.

PMID- 15972645
TI  - B7-independent inhibition of T cells by CTLA-4.
AB  - CTLA-4 is an inhibitory molecule that regulates T cell expansion and
      differentiation. CTLA-4 binding to B7-1/B7-2 is believed to be crucial for its
      inhibitory signal both by competing for CD28 binding to the same ligands and
      aggregating CTLA-4 to deliver negative signals. In this study, we demonstrate
      that B7 binding is not essential for CTLA-4 activity. CTLA-4 knockout T cells are
      hyperresponsive compared with wild-type T cells in B7-free settings. Expression
      of a B7-nonbinding CTLA-4 mutant inhibited T cell proliferation, cytokine
      production, and TCR-mediated ERK activation in otherwise CTLA-4-deficient T
      cells. Finally, transgenic expression of the ligand-nonbinding CTLA-4 mutant
      delayed the lethal lymphoproliferation observed in CTLA-4-deficient mice. These
      results suggest that ligand binding is not essential for the CTLA-4 function and
      supports an essential role for CTLA-4 signaling during T cell activation.

PMID- 15972646
TI  - ICOS contributes to T cell expansion in CTLA-4 deficient mice.
AB  - Both CD28 and ICOS are important costimulatory molecules that promote Ag-specific
      cellular and humoral immune reactions. Whereas CD28 is generally thought to be
      the most important molecule in the initiation of a T cell response, ICOS is
      considered to act during the effector phase. We have investigated the
      contribution of ICOS to T cell responses in the absence of CTLA-4-mediated
      inhibition. Mice lacking CTLA-4, which show spontaneous CD28-mediated CD4(+) T
      cell activation, expansion and differentiation, were treated with antagonistic
      alphaICOS antibodies. Blocking the interaction between ICOS and its ligand B7RP-1
      significantly reduced this aberrant T cell activation and caused a reduction in T
      cell numbers. In vitro analysis of CD4(+) T cells from treated mice revealed that
      ICOS blockade significantly reduced Th1 differentiation, while Th2
      differentiation was only moderately inhibited. Further in vitro stimulation
      experiments demonstrated that ICOS is able to induce proliferation of murine
      CD4(+) and CD8(+) T cells but only in the presence of IL-2. These results
      indicate that ICOS is not only important for T cell effector function but also
      contributes to the expansion phase of a T cell response in the presence of CD28
      signaling.

PMID- 15972647
TI  - Flt3 ligand-generated murine plasmacytoid and conventional dendritic cells differ
      in their capacity to prime naive CD8 T cells and to generate memory cells in
      vivo.
AB  - Mature dendritic cells (DCs) have the capacity to induce efficient primary T cell
      response and effector cell differentiation. Thus, these cells are a major tool in
      the design of various immunotherapeutic protocols. We have tested the capacity of
      different subsets of matured DCs pulsed with a peptide to induce the
      differentiation of naive CD8 T cells into memory cells in vivo. Flt3 ligand (FL)
      induces the differentiation of conventional DCs (cDCs) and plasmacytoid DCs
      (PDCs) from murine bone marrow precursors in vitro. After maturation, both
      subsets become strong stimulators of Ag-specific T cell responses in vitro.
      However, the in vivo T cell stimulatory capacity of these DC subsets has not been
      studied in detail. In the present study, we demonstrate that mature FL-generated
      DCs induce efficient peptide-specific CD8 T cell response and memory cell
      differentiation in vivo. This is mainly due to the cDC subset because the PDC
      subset induced only a negligible primary CD8 response without detectable levels
      of memory CD8 T cell differentiation. Thus, in vitro FL-generated mature cDCs,
      but not PDCs, are potent stimulators of peptide-specific CD8 T cell responses and
      memory generation in vivo.

PMID- 15972648
TI  - CD8alpha+ dendritic cells selectively present MHC class I-restricted noncytolytic
      viral and intracellular bacterial antigens in vivo.
AB  - CD8alpha(+) dendritic cells (DCs) have been shown to be the principal DC subset
      involved in priming MHC class I-restricted CTL immunity to a variety of cytolytic
      viruses, including HSV type 1, influenza, and vaccinia virus. Whether priming of
      CTLs by CD8alpha(+) DCs is limited to cytolytic viruses, which may provide dead
      cellular material for this DC subset, or whether these DCs selectively present
      intracellular Ags, is unknown. To address this question, we examined Ag
      presentation to a noncytolytic virus, lymphocytic choriomeningitis virus, and to
      an intracellular bacterium, Listeria monocytogenes. We show that regardless of
      the type of intracellular infection, CD8alpha(+) DCs are the principal DC subset
      that initiate CD8(+) T cell immunity.

PMID- 15972649
TI  - MHC class I-positive dendritic cells (DC) control CD8 T cell homeostasis in vivo:
      T cell lymphopenia as a prerequisite for DC-mediated homeostatic proliferation of
      naive CD8 T cells.
AB  - The sizes of peripheral T cell pools are regulated by competition for
      environmental signals within a given ecological T cell niche. Cytokines and MHC
      molecules have been identified as resources for which naive T cells compete to
      proliferate homeostatically in lymphopenic hosts to fill up their respective
      compartments. However, it still remains unclear to what extent CD4 and CD8 T
      cells intercompete for these resources and which role dendritic cells (DC) play
      in this scenario. Using transgenic mice in which only DC express MHC class I, we
      demonstrate that this type of APC is sufficient to trigger complete homeostatic
      proliferation of CD8 T cells in vivo. However, normal numbers of endogenous naive
      CD4 T cells, but not CD25(+)CD4(+) T regulatory cells, efficiently suppress this
      expansion in vivo. These findings identify DC as a major resource and a possible
      target for homeostatic competition between naive CD4 and CD8 T cells.

PMID- 15972650
TI  - Evidence that the cellular ligand for the human NK cell activation receptor NKp30
      is not a heparan sulfate glycosaminoglycan.
AB  - NKp30 (NCR3, CD337) is a natural cytotoxicity receptor, expressed on subsets of
      human peripheral blood NK cells, involved in NK cell killing of tumor cells and
      immature dendritic cells. The cellular ligand for NKp30 has remained elusive,
      although evidence that membrane-associated heparan sulfate (HS) proteoglycans are
      involved in the recognition of cellular targets by NKp30 was recently reported.
      The data presented in this report show conclusively that HS glycosaminoglycans
      (GAG) are not ligands for NKp30. We show that removing HS completely from the
      cell surface of human 293-EBNA cells with mammalian heparanase does not affect
      binding of rNKp30/human IgG1 Fc chimera complexes or binding of multimeric
      liposome-rNKp30 complexes. Removing HS from 293-EBNA cells, culture-generated DC,
      MM-170 malignant melanoma cells, or HeLa cells does not affect the NKp30
      dependent killing of these cells by NK cells. We show further that the GAG
      deficient hamster pgsA-745 cells that lack HS and the GAG-expressing parent CHO
      K1 cells are both killed by NK cells, with killing of both cell lines inhibited
      to the same extent by anti-NKp30 mAb. From these results we conclude that HS GAG
      are not ligands for NKp30, leaving open the question as to the nature of the
      cellular ligand for this important NK cell activation receptor.

PMID- 15972651
TI  - The isoforms of phospholipase C-gamma are differentially used by distinct human
      NK activating receptors.
AB  - The two isoforms of phospholipase C (PLC)-gamma couple immune recognition
      receptors to important calcium- and protein kinase C-dependent cellular
      functions. It has been assumed that PLC-gamma1 and PLC-gamma2 have redundant
      functions and that the receptors can use whichever PLC-gamma isoform is
      preferentially expressed in a cell of a given hemopoietic lineage. In this study,
      we demonstrate that ITAM-containing immune recognition receptors can use either
      PLC-gamma1 or PLC-gamma2, whereas the novel NK cell-activating receptor NKG2D
      preferentially couples to PLC-gamma2. Experimental models evaluating signals from
      either endogenous receptors (FcR vs NKG2D-DAP10) or ectopically expressed
      chimeric receptors (with ITAM-containing cytoplasmic tails vs DAP10-containing
      cytoplasmic tails) demonstrate that PLC-gamma1 and PLC-gamma2 both regulate the
      functions of ITAM-containing receptors, whereas only PLC-gamma2 regulates the
      function of DAP10-coupled receptors. These data suggest that specific immune
      recognition receptors can differentially couple to the two isoforms of PLC-gamma.
      More broadly, these observations reveal a basis for selectively targeting the
      functions initiated by distinct immune recognition receptors.

PMID- 15972653
TI  - Effects of natural human antibodies against a nonhuman sialic acid that
      metabolically incorporates into activated and malignant immune cells.
AB  - Humans are genetically incapable of producing the mammalian sialic acid N
      glycolylneuraminic acid (Neu5Gc), due to an inactivating mutation in the enzyme
      synthesizing it. Despite this, human cells and tissues appear capable of
      metabolically incorporating Neu5Gc from exogenous sources, including dietary red
      meat and dairy products. All normal humans studied are now shown to have
      circulating Abs against Neu5Gc, with marked differences in isotype levels. The
      question arises whether such Abs can adversely affect Neu5Gc-expressing human
      cells or tissues. In this study, we show that although normal human PBMC do not
      incorporate Neu5Gc during in vitro incubation, activated T cells do. Primary
      human leukemia cells and human leukemic cell lines are even more efficient at
      incorporation. Human sera containing naturally high levels of anti-Neu5Gc IgG Abs
      (hereafter abbreviated GcIg) deposited complement on Neu5Gc-expressing leukemic
      cells and activated T cells, but not on normal cells. The binding of GcIg
      resulted in complement-mediated cytotoxicity, which was inhibited by heat
      inactivation. Low anti-Neu5Gc IgG-containing human sera did not mediate any of
      these effects. Mixed killing assays confirmed the 15-fold selective killing of
      leukemic cells over PBMC by GcIg following Neu5Gc feeding. This approach could
      potentially serve as novel way to target malignant cells for death in vivo using
      either natural Abs or anti-Neu5Gc Abs prepared for this purpose. Further studies
      are needed to determine whether deposition of natural GcIg and complement can
      also target healthy proliferating immune cells for death in vivo following
      incorporation of dietary Neu5Gc.

PMID- 15972652
TI  - Heat shock protein 65-reactive T cells are involved in the pathogenesis of non
      antigenic dimethyl dioctadecyl ammonium bromide-induced arthritis.
AB  - Dimethyl dioctadecyl ammonium bromide (DDA) (C(38)H(80)NBr) is a nonantigenic
      lipoid material. DDA-induced arthritis (DIA) in the Lewis (LEW) (RT.1(l)) rat is
      a new experimental model for human rheumatoid arthritis (RA). DIA is a T cell
      mediated autoimmune disease. However, the precise self/foreign Ags associated
      with the disease process in DIA are not yet known. We observed that LEW rats with
      DIA spontaneously raised a vigorous T cell response both to 65-kDa self (rat)
      heat shock protein (Rhsp65) and mycobacterial hsp65 (Bhsp65), but not to another
      arthritis-related Ag, bovine collagen type II. The T cell response to Rhsp65 was
      focused predominantly on determinant regions 120-134 and 213-227 of the self
      protein. Interestingly, pretreatment of adult LEW rats using either a mixture of
      peptides 120-134 and 213-227 of Rhsp65 or a low nonarthritogenic dose of DDA
      induced protection against subsequent DIA. Intriguingly, the protection induced
      by the latter was associated with spontaneous priming of T cells specific for
      peptide 213-227 of Rhsp65. Similarly, LEW rats neonatally tolerized against
      either Rhsp65 or Bhsp65 were significantly protected from subsequently induced
      DIA at adult stage, showing the disease-modulating attribute of the hsp65
      specific T cells. Taken together, the above findings demonstrate that the hsp65
      directed T cell repertoire is of significance in the pathogenesis of autoimmune
      arthritis induced by nonantigenic DDA. Like other animal models of RA involving
      hsp65, these first insights into the disease-associated Ags in the DIA model
      would pave the way for further understanding of the immunological aspects of
      induction and regulation of RA.

PMID- 15972654
TI  - Spermine, a natural polyamine, suppresses LFA-1 expression on human lymphocyte.
AB  - Natural polyamines, spermine, spermidine, and putrescine, play a pivotal role in
      the regulation of gene expression; therefore, the age-dependent decreases and the
      disease-dependent increases in polyamine synthesis suggest a possible
      contribution of polyamines to the age-related and disease-associated changes in
      cellular function. In this study, we examined the effects of polyamines on the
      cellular function and the expression of adhesion molecules on human PBMCs from
      healthy volunteers. Flow cytometry revealed that PBMCs cultured with spermine
      decreased mean fluorescent intensities (MFIs) of CD11a and CD18 in the lymphocyte
      light-scattered region, but not in the monocyte region. This suppression was
      observed in a dose- and time-dependent manner and found nonspecifically on all
      cell subsets we tested (CD3(+), CD4(+), CD8(+), CD19(+), CD45RA(+), CD45RO(+),
      CD4(+)CD45RA(+), CD4(+)CD45RO(+), CD8(+)CD45RA(+), CD8(+)CD45RO(+)). The
      decreases of CD11a and CD18 MFIs were accompanied by the decrease in adherent
      capacity of PBMCs to HUVECs. Spermine did not hinder cell activities or cell
      viability. Among 42 healthy volunteers (mean, 49.5 years old; from 26 to 69),
      blood spermine levels inversely correlated with the CD11a MFIs of cells in the
      lymphocyte region (r = -0.48; p = 0.001), but not with those in the monocyte
      region. The effects of spermidine seemed weaker than those of spermine, and blood
      spermidine levels had no correlation with CD11a MFIs of the lymphocyte region.
      Putrescine had no effect on the expressions of membrane molecules. Polyamines,
      especially spermine, decrease LFA-1 (CD11a/CD18) expression on human lymphocyte
      and adhesion capacity of PBMCs to HUVECs.

PMID- 15972655
TI  - Peripheral CD8+CD25+ T lymphocytes from MHC class II-deficient mice exhibit
      regulatory activity.
AB  - We characterized CD8(+) T cells constitutively expressing CD25 in mice lacking
      the expression of MHC class II molecules. We showed that these cells are present
      not only in the periphery but also in the thymus. Like CD4(+)CD25(+) T cells,
      CD8(+)CD25(+) T cells appear late in the periphery during ontogeny. Peripheral
      CD8(+)CD25(+) T cells from MHC class II-deficient mice also share phenotypic and
      functional features with regulatory CD4(+)CD25(+) T cells: in particular, they
      strongly express glucocorticoid-induced TNFR family-related gene, CTLA-4 and
      Foxp3, produce IL-10, and inhibit CD25(-) T cell responses to anti-CD3
      stimulation through cell contacts with similar efficiency to CD4(+)CD25(+) T
      cells. However, unlike CD4(+)CD25(+) T cells CD8(+)CD25(+) T cells from MHC class
      II-deficient mice strongly proliferate and produce IFN-gamma in vitro in response
      to stimulation in the absence of exogenous IL-2.

PMID- 15972656
TI  - Refining the rules of gliadin T cell epitope binding to the disease-associated
      DQ2 molecule in celiac disease: importance of proline spacing and glutamine
      deamidation.
AB  - Celiac disease is driven by intestinal T cells responsive to proline-rich gluten
      peptides that often harbor glutamate residues formed by tissue transglutaminase
      mediated glutamine conversion. The disease is strongly associated with the HLA
      variant DQ2.5 (DQA1*05, DQB1*02), and intestinal gluten-reactive T cells from
      DQ2.5-positive patients are uniquely restricted by this HLA molecule. In this
      study, we describe the mapping of two novel T cell epitopes of gamma-gliadin and
      the experimental identification of the DQ2.5 binding register of these and three
      other gamma-gliadin epitopes. The new data extend the knowledge base for
      understanding the binding of gluten peptides to DQ2.5. The alignment of the
      experimentally determined binding registers of nine gluten epitopes reveal
      positioning of proline residues in positions P1, P3, P6, and P8 but never in
      positions P2, P4, P7, and P9. Glutamate residues formed by tissue
      transglutaminase-mediated deamidation are found in position P1, P4, P6, P7, or
      P9, but only deamidations in positions P4 and P6, and rarely in P7, seem to be
      crucial for T cell recognition. The majority of these nine epitopes are
      recognized by celiac lesion T cells when presented by the related but
      nonassociated DQ2.2 (DQA1*0201, DQB1*02) molecule. Interestingly, the DQ2.2
      presentation for most epitopes is less efficient than presentation by the DQ2.5
      molecule, and this is particularly prominent for the alpha-gliadin epitopes.
      Contrary to previous findings, our data do not show selective presentation of
      DQ2.5 over DQ2.2 for gluten epitopes that carry proline residues at the P3
      position.

PMID- 15972657
TI  - Dual effects of p38 MAPK on TNF-dependent bronchoconstriction and TNF-independent
      neutrophil recruitment in lipopolysaccharide-induced acute respiratory distress
      syndrome.
AB  - The administration of endotoxins from Gram-negative bacteria induces
      manifestations reminding of acute respiratory distress syndrome. p38 MAPKs have
      been implicated in this pathology. In this study, we show that the specific p38
      alpha,beta MAPK inhibitor, compound 37, prevents LPS-induced bronchoconstriction
      and neutrophil recruitment into the lungs and bronchoalveolar space in a dose
      dependent manner in C57BL/6 mice. Furthermore, TNF induction and TNF signals were
      blocked. In TNF-deficient mice, bronchoconstriction, but not neutrophil
      sequestration, in the lung was abrogated after LPS administration. Therefore, TNF
      inhibition does not explain all of the effects of the p38 MAPK inhibitor. The p38
      alpha,beta MAPK inhibitor also prevented LPS-induced neutrophilia in TNF
      deficient mice. In conclusion, LPS provokes acute bronchoconstriction that is TNF
      dependent and p38 MAPK mediated, whereas the neutrophil recruitment is
      independent of TNF but depends on LPS/TLR4-induced signals mediated by p38 MAPK.

PMID- 15972658
TI  - The CD3epsilon proline-rich sequence, and its interaction with Nck, is not
      required for T cell development and function.
AB  - The CD3epsilon proline-rich sequence (PRS) binds to the cytosolic adaptor
      molecule Nck after TCR ligation. It has been proposed that this interaction is
      essential for immunological synapse formation and T cell activation. To assess
      the physiological importance of the CD3epsilon PRS, we have generated mice that
      lack this motif (CD3epsilon.PRS(M)). Pull-down experiments demonstrated the
      inability of Nck to bind to the CD3epsilon PRS in thymocytes from mutant mice
      after TCR ligation. Surprisingly, no differences were observed in the number and
      percentage of T cell subsets in the thymus and spleen, and there was no apparent
      defect in positive or negative selection. Furthermore, the proliferative response
      of CD3epsilon.PRS(M) T cells to staphylococcal enterotoxin B and anti-CD3 Ab was
      normal. TCR surface expression, constitutive internalization, and Ag-induced down
      modulation were also normal. These data suggest that the interaction between the
      CD3epsilon PRS and Nck, or any other Src homology 3 domain-containing molecule,
      is not essential for T cell development and function.

PMID- 15972660
TI  - TLR-dependent activation stimuli associated with Th1 responses confer NK cell
      stimulatory capacity to mouse dendritic cells.
AB  - Dendritic cells (DCs) have an important role in the activation of NK cells that
      exert direct antitumor and antimicrobial effects and can influence the
      development of adaptive T cell responses. DCs acquire NK cell stimulatory
      capacity after exposure to various stimuli. In this study we investigated the
      nature of the stimuli that confer to DCs the NK cell-activating capacity. After
      exposure of DCs to TLR-dependent and -independent microbial stimuli and to
      nonmicrobial stimuli, we evaluated the ability of activated DCs to elicit IFN
      gamma production from NK cells in vitro and to promote NK cell activation in
      vivo. We show in this study that only TLR-dependent microbial stimuli typically
      associated with Th1 responses confer to DCs the ability to activate NK cells,
      whereas stimuli associated with Th2 responses do not have this property.

PMID- 15972659
TI  - Heat shock protein 60 activates cytokine-associated negative regulator suppressor
      of cytokine signaling 3 in T cells: effects on signaling, chemotaxis, and
      inflammation.
AB  - Previously, we reported that treatment of T cells with the 60-kDa heat shock
      protein (HSP60) inhibits chemotaxis. We now report that treatment of purified
      human T cells with recombinant human HSP60 or its biologically active peptide
      p277 up-regulates suppressor of cytokine signaling (SOCS)3 expression via TLR2
      and STAT3 activation. SOCS3, in turn, inhibits the downstream effects of stromal
      cell-derived-1alpha (CXCL12)-CXCR4 interaction in: 1) phosphorylation of ERK1/2,
      Pyk2, AKT, and myosin L chain, required for cell adhesion and migration; 2)
      formation of rear-front T cell polarity; and 3) migration into the bone marrow of
      NOD/SCID mice. HSP60 also activates SOCS3 in mouse lymphocytes and inhibits their
      chemotaxis toward stromal cell-derived factor-1alpha and their ability to
      adoptively transfer delayed-type hypersensitivity. These effects of HSP60 could
      not be attributed to LPS or LPS-associated lipoprotein contamination. Thus, HSP60
      can regulate T cell-mediated inflammation via specific signal transduction and
      SOCS3 activation.

PMID- 15972661
TI  - Transgenic expression of dominant-negative Fas-associated death domain protein in
      beta cells protects against Fas ligand-induced apoptosis and reduces spontaneous
      diabetes in nonobese diabetic mice.
AB  - In type 1 diabetes, many effector mechanisms damage the beta cell, a key one
      being perforin/granzyme B production by CD8(+) T cells. The death receptor
      pathway has also been implicated in beta cell death, and we have therefore
      generated NOD mice that express a dominant-negative form of the Fas-associated
      death domain protein (FADD) adaptor to block death receptor signaling in beta
      cells. Islets developed normally in these animals, indicating that FADD is not
      necessary for beta cell development as it is for vasculogenesis. beta cells from
      the transgenic mice were resistant to killing via the Fas pathway in vitro. In
      vivo, a reduced incidence of diabetes was found in mice with higher levels of
      dominant-negative FADD expression. This molecule also blocked signals from the IL
      1R in culture, protecting isolated islets from the toxic effects of cytokines and
      also marginally reducing the levels of Fas up-regulation. These data support a
      role for death receptors in beta cell destruction in NOD mice, but blocking the
      perforin/granzyme pathway would also be necessary for dominant-negative FADD to
      have a beneficial clinical effect.

PMID- 15972662
TI  - HIV type 1 glycoprotein 120 inhibits human B cell chemotaxis to CXC chemokine
      ligand (CXCL) 12, CC chemokine ligand (CCL)20, and CCL21.
AB  - We analyzed the modulation of human B cell chemotaxis by the gp120 proteins of
      various HIV-1 strains. X4 and X4/R5 gp120 inhibited B cell chemotaxis toward
      CXCL12, CCL20, and CCL21 by 40-50%, whereas R5 gp120 decreased inhibition by 20%.
      This gp120-induced inhibition was strictly dependent on CXCR4 or CCR5 and lipid
      rafts but not on CD4 or V(H)3-expressing BCR. Inhibition did not impair the
      expression or ligand-induced internalization of CCR6 and CCR7. Our data suggest
      that gp120/CXCR4 and gp120/CCR5 interactions lead to the cross-desensitization of
      CCR6 and CCR7 because gp120 does not bind CCR6 and CCR7. Unlike CXCL12, gp120 did
      not induce the activation of phospholipase Cbeta3 and PI3K downstream from CXCR4,
      whereas p38 MAPK activation was observed. Similar results were obtained if gp120
      treated cells were triggered by CCL21 and CCL20. Our results are consistent with
      a blockade restricted to signaling pathways using phosphatidylinositol-4,5
      bisphosphate as a substrate. X4 and X4/R5 gp120 induced the cleavage of CD62
      ligand by a mechanism dependent on matrix metalloproteinase 1 and 3, CD4, CXCR4,
      Galpha(i), and p38 MAPK, whereas R5 gp120 did not. X4 and X4/R5 gp120 also
      induced the relocalization of cytoplasmic CD95 to the membrane and a 23% increase
      in CD95-mediated apoptosis. No such effects were observed with R5 gp120. The
      gp120-induced decrease in B cell chemotaxis and CD62 ligand expression, and
      increase in CD95-mediated B cell apoptosis probably have major deleterious
      effects on B cell responsiveness during HIV infection and in vaccination trials.

PMID- 15972663
TI  - Cellular FLIP long form augments caspase activity and death of T cells through
      heterodimerization with and activation of caspase-8.
AB  - Caspase activity is required not only for the death of T cells, but also for
      their activation. A delicate balance of caspase activity is thus required during
      T cell activation at a level that will not drive cell death. How caspase activity
      is initiated and regulated during T cell activation is not known. One logical
      candidate for this process is cellular FLIP long form (c-FLIP(L)), because it can
      block caspase-8 recruitment after Fas (CD95) ligation as well as directly
      heterodimerize with and activate caspase-8. The current findings demonstrate that
      after T cell activation, caspase-8 and c-FLIP(L) associate in a complex enriched
      for active caspases. This occurs coincidently with the cleavage of two known
      caspase-8 substrates, c-FLIP(L) and receptor interacting protein 1. Caspase
      activity is higher in wild-type CD8(+) than CD4(+) effector T cells. Increased
      expression of c-FLIP(L) results in augmented caspase activity in resting and
      effector T cells to levels that provoke cell death, especially of the CD8 subset.
      c-FLIP(L) is thus not only an inhibitor of cell death by Fas, it can also act as
      a principal activator of caspases independently of Fas.

PMID- 15972664
TI  - deltaBAFF, a splice isoform of BAFF, opposes full-length BAFF activity in vivo in
      transgenic mouse models.
AB  - DeltaBAFF is a novel splicing isoform of the regulator B cell-activating factor
      (BAFF, BLyS), a TNF family protein with powerful immunoregulatory effects.
      Overexpression of BAFF leads to excessive B cell accumulation, activation,
      autoantibodies, and lupus-like disease, whereas an absence of BAFF causes
      peripheral B cell immunodeficiency. Based on the ability of DeltaBAFF to
      multimerize with full-length BAFF and to limit BAFF proteolytic shedding from the
      cell surface, we previously proposed a role for DeltaBAFF in restraining the
      effects of BAFF and in regulating B lymphocyte homeostasis. To test these ideas
      we generated mice transgenic for DeltaBAFF under the control of human CD68
      regulatory elements, which target expression to myeloid and dendritic cells. We
      also generated in parallel BAFF transgenic mice using the same expression
      elements. Analysis of the transgenic mice revealed that DeltaBAFF and BAFF had
      opposing effects on B cell survival and marginal zone B cell numbers. DeltaBAFF
      transgenic mice had reduced B cell numbers and T cell-dependent Ab responses, but
      normal preimmune serum Ig levels. In contrast, BAFF transgenic mice had
      extraordinarily elevated Ig levels and increases in subsets of B cells.
      Unexpectedly, both BAFF and DeltaBAFF appeared to modulate the numbers of B-1
      phenotype B cells.

PMID- 15972665
TI  - Linked foreign T-cell help activates self-reactive CTL and inhibits tumor growth.
AB  - Transgenic mice expressing membrane-bound OVA under the rat insulin promoter, RIP
      mOVA, has previously been suggested to display deletional tolerance toward the
      dominant CTL epitope, SIINFEKL, and provide an elegant model system to test the
      hypothesis that the lack of T cell help contributes to the tolerance. To
      understand how the CD8 tolerance is maintained in these mice, a set of neo-self
      Ags, OVA, modified to contain a foreign Th peptide, were constructed and tested
      for their ability to induce CTL responses in RIP-mOVA mice. Immunization with
      these Th peptide-modified OVA molecules and not with the wild-type OVA induced
      self-reactive CTLs recognizing dominant CTL peptide, SIINFEKL. Importantly,
      immunization with the modified OVA constructs also prevented the growth of OVA
      expressing tumors in transgenic mice. Since endogenous OVA Th peptides did not
      contribute toward breaking self CTL tolerance, these results also highlighted a
      very robust CD4 T cell tolerance toward OVA in RIP-mOVA mice that has not been
      previously described. These results therefore provide direct evidence that it is
      the tolerance in the CD4 Th cell compartment that helps maintain the CTL
      tolerance against self-Ag in these mice. Since the CTL tolerance can be broken or
      bypassed by foreign Th peptides inserted into a self Ag, potential of using this
      approach in generating effective therapeutic cancer vaccines is discussed.

PMID- 15972666
TI  - IL-9 promotes but is not necessary for systemic anaphylaxis.
AB  - Anaphylaxis represents an extreme form of allergic reaction, consisting of a
      sensitization phase during which allergen-specific IgE are produced and an acute
      effector phase triggered by allergen-induced degranulation of mast cells. We
      studied the role of IL-9, a Th2 cytokine implicated in asthma, in different
      models of murine anaphylaxis. Using a passive model of systemic anaphylaxis, in
      which anti-DNP IgE Abs were administered before challenge with DNP-BSA, we found
      that IL-9-transgenic mice or wild-type mice treated with IL-9 for 5 days were
      highly sensitive to fatal anaphylaxis. This effect was reproduced in both
      anaphylaxis-susceptible and -resistant backgrounds (FVB/N or [FVB/N x BALB/c]
      F(1) mice, respectively) and correlated with increased serum concentrations of
      mouse mast cell protease-1 level, a protein released upon mast cells
      degranulation. By contrast, IL-9 did not increase the susceptibility to passive
      cutaneous anaphylaxis. IL-9 expression also increased the susceptibility to fatal
      anaphylaxis when mice were sensitized by immunization against OVA before
      challenge with the same Ag. In this model, serum from sensitized, IL-9-transgenic
      mice was more potent in transferring susceptibility to OVA challenge into naive
      mice, indicating that IL-9 also promotes the sensitization stage. Finally, using
      IL-9R-deficient mice, we found that despite its anaphylaxis-promoting activity,
      IL-9 is dispensable for development of both passive and active anaphylaxis, at
      least in the C57BL/6 mouse background. Taken together, the data reported in this
      study indicate that IL-9 promotes systemic anaphylaxis reactions, acting at both
      the sensitization and effector stages, but is not absolutely required for this
      process.

PMID- 15972668
TI  - Integrin regulation by RhoA in thymocytes.
AB  - The guanine nucleotide-binding protein Rho has essential functions in T cell
      development and is important for the survival and proliferation of T cell
      progenitors in the thymus. To explore the mechanisms used by RhoA to control
      thymocyte biology, the role of this GTPase in the regulation of integrin-mediated
      cell adhesion was examined. The data show that RhoA activation is sufficient to
      stimulate beta(1) and beta(2) integrin-mediated adhesion in murine thymocytes.
      RhoA is also needed for integrin activation in vivo as loss of Rho function
      impaired the ability of thymocytes to adhere to the extracellular matrix protein
      VCAM-1 and prevented integrin activation induced by the GTPases Rac-1 and Rap1A
      in vivo. The regulated activity of integrins is needed for cell motility and in
      the present study it was seen that RhoA activity is critical for integrin
      mediated thymocyte migration to chemokines in vitro. Thus, RhoA has a critical
      role in regulating cell adhesion and migration during T cell development.

PMID- 15972667
TI  - Macrophages sequentially change their functional phenotype in response to changes
      in microenvironmental influences.
AB  - Recent studies have described the development of distinct functional subsets of
      macrophages in association with cancer, autoimmune disease, and chronic
      infections. Based on the ability of Th1 vs Th2 cytokines to promote opposing
      activities in macrophages, it has been proposed that macrophages develop into
      either type 1 inflammatory or type 2 anti-inflammatory subsets. As an alternative
      to the concept of subset development, we propose that macrophages, in response to
      changes in their tissue environment, can reversibly and progressively change the
      pattern of functions that they express. As demonstrated herein, macrophages can
      reversibly shift their functional phenotype through a multitude of patterns in
      response to changes in cytokine environment. Macrophages display distinct
      functional patterns after treatment with IFN-gamma, IL-12, IL-4, or IL-10 and
      additional functional patterns are displayed depending on whether the cytokine is
      present alone or with other cytokines and whether the cytokines are added before
      or concomitantly with the activating stimulus (LPS). Sequential treatment of
      macrophages with multiple cytokines results in a progression through multiple
      functional phenotypes. This ability to adapt to changing cytokine environments
      has significant in vivo relevance, as evidenced by the demonstration that
      macrophage functional phenotypes established in vivo in aged or tumor-bearing
      mice can be altered by changing their microenvironment. A concept of functional
      adaptivity is proposed that has important implications for therapeutic targeting
      of macrophages in chronic diseases that result in the dominance of particular
      functional phenotypes of macrophages that play a significant role in disease
      pathology.

PMID- 15972669
TI  - The unique region of surrogate light chain component lambda5 is a heavy chain
      specific regulator of precursor B cell receptor signaling.
AB  - Signals transduced by precursor-BCRs (pre-BCRs) composed of Ig mu heavy chains
      (HCs) and the surrogate L chain components lambda5 and VpreB are critical for B
      cell development. A conserved unique region (UR) of lambda5 was shown to activate
      pre-BCR complexes in transformed cells and to engage putative ligands, but its
      contribution to pre-B cell development is not known. It is also not clear why the
      lambda-like sequences in lambda5 are used to select HCs that will associate
      mainly with kappa L chains. In this study, we show that, in transformed and
      primary mouse B cell progenitors, receptors containing full-length HCs and
      lacking the lambda5UR were expressed at higher surface levels, but exhibited
      reduced activity compared with normal pre-BCRs in supporting developmental
      changes that accompany the progenitor to pre-B cell transition in primary cell
      culture systems and in the bone marrow in vivo. In contrast, deletion of the
      lambda5UR did not change net signaling output by the Dmu-pre-BCR, a
      developmentally defective receptor that exhibited impaired activity in the
      primary cell culture system. Moreover, the lambda-like sequences in lambda5 were
      more accommodating than kappa in supporting surface expression and signaling by
      the different HCs. These results show that the lambda5UR is important, although
      not essential, for surrogate L chain-dependent receptor signaling in primary
      cells, and furthermore may help allow discrimination of signaling competency
      between normal and Dmu-pre-BCRs. That the lambda-like portion of lambda5 in the
      absence of the UR was nondiscriminatory suggests that the lambda5UR focuses pre
      BCR-dependent selection on the HC V region.

PMID- 15972670
TI  - Rhesus macaque MHC class I molecules present HLA-B-like peptides.
AB  - SIV-infected Indian rhesus macaques (Macaca mulatta) are an important animal
      model for humans infected with HIV. Understanding macaque (M. mulatta class I
      (Mamu)) MHC class I-peptide binding facilitates the comparison of SIV- and HIV
      specific cellular immune responses. In this study, we characterized the
      endogenous peptide-binding properties of three Mamu-A (A*02, A*08, A*11) and
      three Mamu-B (B*01, B*03, B*12) class I molecules. Motif comparisons revealed
      that five of the six macaque class I molecules (A*02, A*08, A*11, B*01, and B*03)
      have peptide-binding motifs similar to those of human class I molecules. Of the
      65 macaque endogenous peptide ligands that we sequenced by tandem mass
      spectroscopy, 5 were previously eluted from HLA class I molecules. Nonamers
      predominated among the individual ligands, and both the motifs and the individual
      ligands indicated P2, P9, and various ancillary anchors. Interestingly, peptide
      binding of the Mamu-A and Mamu-B molecules exhibited cross-species peptide
      presentation overlap primarily with HLA-B molecules. Indeed, all of the macaque
      class I molecules appeared HLA-B-like in peptide presentation. Remarkably, the
      overlap in macaque- and HLA-peptide presentation occurred despite divergent class
      I peptide-binding grooves. Macaque and human class I differing by up to 42 aa (13
      23%) within the alpha-1 and alpha-2 domains, including substantial divergence
      within specificity pockets A-F, bound the same endogenous peptide. Therefore,
      endogenous peptide characterization indicates that macaque class I molecules may
      be the functional equivalents of HLA-B molecules.

PMID- 15972672
TI  - The chicken leukocyte receptor complex: a highly diverse multigene family
      encoding at least six structurally distinct receptor types.
AB  - The chicken Ig-like receptors (CHIR) have been described as two Ig domain
      molecules with long cytoplasmic tails containing inhibitory motifs. In this
      study, we demonstrate that CHIR form a large family, with multiple members
      showing great sequence variability among members as well as a great diversity in
      domain organization and properties of the transmembrane and cytoplasmic segments.
      We characterize various novel receptor types with motifs indicative of
      inhibitory, activating, or both functions. In addition to the inhibitory
      receptors with two ITIM, receptors with a single immunoreceptor tyrosine-based
      switch motif or receptors lacking a cytoplasmic domain were isolated. Activating
      receptors with a short cytoplasmic domain and a transmembrane arginine assembled
      with the newly identified chicken FcepsilonRIgamma chain. Three bifunctional
      receptor types were characterized composed of one or two C2-type Ig-like domains,
      a transmembrane region with a positively charged residue and combinations of
      cytoplasmic motifs such as ITIM, immunoreceptor tyrosine-based switch motif, and
      YXXM. RT-PCR revealed distinct expression patterns of individual CHIR. All
      receptor types shared a conserved genomic architecture, and in single Ig domain
      receptors a pseudoexon replaced the second Ig exon. Southern blot analyses with
      probes specific for the Ig1 domain were indicative of a large multigene family.
      Of 103 sequences from the Ig1 domain of a single animal, 41 unique sequences were
      obtained that displayed extensive variability within restricted Ig regions.
      Fluorescence in situ hybridization localized the CHIR gene cluster to
      microchromosome 31 and identified this region as orthologous to the human
      leukocyte receptor complex.

PMID- 15972671
TI  - Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4:
      linking innate and adaptive immune responses.
AB  - IgA Abs help to maintain homeostasis at mucosal surfaces by promoting defense
      mechanisms that protect against pathogens while suppressing inflammatory
      responses to commensal organisms and food Ags. The polymeric Ig receptor (pIgR)
      mediates transport of IgA across mucosal epithelial cells. We hypothesized that
      signaling through TLRs may up-regulate pIgR expression by intestinal epithelial
      cells and thus enhance IgA-mediated homeostasis. To test this hypothesis we
      treated the HT29 human intestinal epithelial cell line with dsRNA, a ligand for
      TLR3, or LPS, a ligand for TLR4. Both dsRNA and LPS up-regulated levels of pIgR
      mRNA and cell surface pIgR protein. By contrast, dsRNA but not LPS up-regulated
      expression of TLR3 and TLR4 mRNA. However, cell surface expression of both TLR3
      and TLR4 was enhanced by treatment of HT29 cells with their respective ligands.
      Transfection of HT29 cells with wild-type and mutated promoter/enhancer plasmids
      suggested that TLR3 and TLR4 signal primarily through NF-kappaB to enhance
      transcription of pIgR mRNA. TLR3 signaling resulted in a more pronounced
      inflammatory response than did TLR4, as evidenced by up-regulation of the
      transcription factor IFN regulatory factor-1, chemokines IL-8 and RANTES, and the
      proinflammatory cytokine TNF. Signaling through LPS/TLR4 appears to up-regulate
      pIgR expression while minimizing proinflammatory responses, a mechanism that
      could promote IgA-mediated homeostasis in the presence of commensal Gram-negative
      bacteria.

PMID- 15972673
TI  - Simultaneous Th1-type cytokine expression is a signature of peritoneal CD4+
      lymphocytes responding to infection with Listeria monocytogenes.
AB  - The robust murine response to infection with Listeria monocytogenes makes an
      excellent model to study the functional development of immune cells. We
      investigated the cellular immune response to i.p. infection using intracellular
      cytokine staining to identify Ag-specific lymphocytes. CD4(+) peritoneal exudate
      cells obtained 10 days postinfection predominantly coexpressed TNF-alpha, IFN
      gamma, and IL-2 after polyclonal or Ag stimulation. A population of cells
      simultaneously making TNF-alpha and IFN-gamma was also detected but at a lower
      frequency. By following the kinetics of the response to Listeria, we found that
      CD4(+) lymphocytes coexpressing TNF-alpha and IFN-gamma dominated on day 6
      postinfection and then declined. From days 10-27, TNF-alpha(+)IFN-gamma(+)IL-2(+)
      (triple-positive) was the most prevalent cytokine phenotype, and the frequency
      steadily declined. These characteristic cytokine expression patterns were
      observed in both primary and secondary responses to Listeria infection and
      developed even when infection was terminated with antibiotic treatment. A
      cytokine-assisted immunization procedure resulted in both double- and triple
      positive cells, but the clear predominance of triple-positive cells required
      Listeria infection. Triple-positive cells were preferentially noted in the
      peritoneal cavity tissue site; spleen cells displayed a predominant population of
      double-positive T cells (TNF-alpha(+)IFN-gamma(+)). We speculate that the
      appearance of triple-positive cells represents a functionally significant subset
      important in host defense at nonlymphoid tissue sites.

PMID- 15972674
TI  - Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related
      oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium:
      implications for airway inflammation in cystic fibrosis.
AB  - IL-17R signaling is critical for pulmonary neutrophil recruitment and host
      defense against Gram-negative bacteria through the coordinated release of G-CSF
      and CXC chemokine elaboration. In this study, we show that IL-17R is localized to
      basal airway cells in human lung tissue, and functional IL-17R signaling occurs
      on the basolateral surface of human bronchial epithelial (HBE) cells. IL-17A and
      IL-17F were potent inducers of growth-related oncogene-alpha and G-CSF in HBE
      cells, and significant synergism was observed with TNF-alpha largely due to
      signaling via TNFRI. The activities of both IL-17A and IL-17F were blocked by a
      specific anti-IL-17R Ab, but only IL-17A was blocked with a soluble IL-17R,
      suggesting that cell membrane IL-17R is required for signaling by both IL-17A and
      IL-17F. Because IL-17A and IL-17F both regulate lung neutrophil recruitment, we
      measured these molecules as well as the proximal regulator IL-23p19 in the sputum
      of patients with cystic fibrosis (CF) undergoing pulmonary exacerbation. We found
      significantly elevated levels of these molecules in the sputum of patients with
      CF who were colonized with Pseudomonas aeruginosa at the time of pulmonary
      exacerbation, and the levels declined with therapy directed against P.
      aeruginosa. IL-23 and the downstream cytokines IL-17A and IL-17F are critical
      molecules for proinflammatory gene expression in HBE cells and are likely
      involved in the proinflammatory cytokine network involved with CF pathogenesis.

PMID- 15972675
TI  - Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by
      Nipah virus envelope glycoproteins and augments dendritic cell secretion of
      proinflammatory cytokines.
AB  - Galectin-1 (gal-1), an endogenous lectin secreted by a variety of cell types, has
      pleiotropic immunomodulatory functions, including regulation of lymphocyte
      survival and cytokine secretion in autoimmune, transplant disease, and parasitic
      infection models. However, the role of gal-1 in viral infections is unknown.
      Nipah virus (NiV) is an emerging pathogen that causes severe, often fatal,
      febrile encephalitis. The primary targets of NiV are endothelial cells. NiV
      infection of endothelial cells results in cell-cell fusion and syncytia formation
      triggered by the fusion (F) and attachment (G) envelope glycoproteins of NiV that
      bear glycan structures recognized by gal-1. In the present study, we report that
      NiV envelope-mediated cell-cell fusion is blocked by gal-1. This inhibition is
      specific to the Paramyxoviridae family because gal-1 did not inhibit fusion
      triggered by envelope glycoproteins of other viruses, including two retroviruses
      and a pox virus, but inhibited fusion triggered by envelope glycoproteins of the
      related Hendra virus and another paramyxovirus. The physiologic dimeric form of
      gal-1 is required for fusion inhibition because a monomeric gal-1 mutant had no
      inhibitory effect on cell fusion. gal-1 binds to specific N-glycans on NiV
      glycoproteins and aberrantly oligomerizes NiV-F and NiV-G, indicating a mechanism
      for fusion inhibition. gal-1 also increases dendritic cell production of
      proinflammatory cytokines such as IL-6, known to be protective in the setting of
      other viral diseases such as Ebola infections. Thus, gal-1 may have direct
      antiviral effects and may also augment the innate immune response against this
      emerging pathogen.

PMID- 15972676
TI  - Listeria-infected myeloid dendritic cells produce IFN-beta, priming T cell
      activation.
AB  - The intracellular bacterium Listeria monocytogenes infects dendritic cells (DC)
      and other APCs and induces potent cell-mediated protective immunity. However,
      heat-killed bacteria fail to do so. This study explored whether DC differentially
      respond to live and killed Listeria and how this affects T cell activation. To
      control for bacterial number, a replication-deficient strain, Lmdd, defective in
      D-alanine biosynthesis, was used. We found that DC internalize both live and heat
      killed Lmdd and similarly up-regulate the expression of costimulatory molecules,
      a necessary step for T cell activation. However, only live Lmdd-infected DC
      stimulate T cells to express the early activation marker CD69 and enhance T cell
      activation upon TCR engagement. Infection with live, but not heat-killed, Lmdd
      induces myeloid DC to secrete copious amounts of IFN-beta, which requires
      bacterial cytosolic invasion. Exposure to high concentrations of IFN-beta
      sensitizes naive T cells for Ag-dependent activation.

PMID- 15972677
TI  - Human-like immune responses in CD46 transgenic mice.
AB  - Neisseria meningitidis is a major cause of sepsis and/or meningitis. These
      bacteria normally cause disease only in humans, however, mice expressing human
      CD46 are susceptible to meningococcal disease. To explain the sensitivity of CD46
      transgenic mice to meningococci, we evaluated early immune responses. Stimulation
      of TNF, IL-6, and IL-10 was stronger in CD46 transgenic mice compared with
      nontransgenic mice, and resembled human responses. In CD46 transgenic mice,
      bacterial clearance in blood started at later time points, and neutrophil numbers
      in blood were lower compared with nontransgenic mice. Further, elevated levels of
      activated microglia cells and cyclooxygenase-2 were observed in brain of infected
      CD46 transgenic mice. Intraperitoneal administration of meningococci lead to
      increased levels of macrophages only in the i.p. cavity of CD46 transgenic mice.
      Most of the responses were impaired or absent using LPS-deficient meningococci,
      showing the importance of LPS in the early immune response to meningococcal
      infection. Taken together, these data demonstrate that responses in mice
      expressing human CD46 mimic human meningococcal disease in many aspects, and
      demonstrate novel important links between CD46 and the innate immune system.

PMID- 15972678
TI  - DNA augments antigenicity of mycobacterial DNA-binding protein 1 and confers
      protection against Mycobacterium tuberculosis infection in mice.
AB  - Mycobacterium consists up to 7% of mycobacterial DNA-binding protein 1 (MDP1) in
      total cellular proteins. Host immune responses to MDP1 were studied in mice to
      explore the antigenic properties of this protein. Anti-MDP1 IgG was produced
      after infection with either bacillus Calmette-Guerin or Mycobacterium
      tuberculosis in C3H/HeJ mice. However, the level of Ab was remarkably low when
      purified MDP1 was injected. MDP1 is considered to be associated with DNA in
      nucleoid, which contains immunostimulatory CpG motif. Therefore, we examined
      coadministration of MDP1 and DNA derived from M. tuberculosis. Consequently, this
      procedure significantly enhanced the production of MDP1-specific IgG. Five
      nanograms of DNA was enough to enhance MDP1-specific IgG production in the
      administration of 5 microg of MDP1 into mice. Strong immune stimulation by such a
      small amount of DNA is noteworthy, because >1,000- to 100,000-fold doses of CpG
      DNAs are used for immune activation. A synthetic peptide-based study showed that
      B cell epitopes were different between mice administered MDP1 alone and those
      given a mixture of MDP1 and DNA, suggesting that DNA alters the three-dimensional
      structure of MDP1. Coadministration of DNA also enhanced MDP1-specific IFN-gamma
      production and reduced the bacterial burden of a following challenge of M.
      tuberculosis, showing that MDP1 is a novel vaccine target. Finally, we found that
      MDP1 remarkably enhanced TLR9-dependent immune stimulation by unmethylated CpG
      oligo DNA in vitro. To our knowledge, MDP1 is the first protein discovered that
      remarkably augments the CpG-mediated immune response and is a potential adjuvant
      for CpG DNA-based immune therapies.

PMID- 15972679
TI  - Chlamydia trachomatis induces expression of IFN-gamma-inducible protein 10 and
      IFN-beta independent of TLR2 and TLR4, but largely dependent on MyD88.
AB  - IFN-gamma-inducible protein 10 (IP-10) is a chemokine important in the attraction
      of T cells, which are essential for resolution of chlamydial genital tract
      infection. During infections with Gram-negative bacteria, the IP-10 response
      mediated through type I IFNs usually occurs as a result of TLR4 stimulation by
      bacterial LPS. However, we found that levels of IP-10 in genital tract secretions
      of Chlamydia trachomatis-infected female wild-type mice were similar to those of
      infected TLR2- and TLR4-deficient mice but significantly greater than those of
      infected MyD88-deficient mice. We investigated the mechanism of IP-10 and IFN
      beta induction during chlamydial infection using mouse macrophages and
      fibroblasts infected ex vivo. The induction of IP-10 and IFN-beta was unchanged
      in Chlamydia-infected TLR2- and TLR4-deficient cells compared with wild-type
      cells. However, infection of MyD88-deficient cells resulted in significantly
      decreased responses. These results suggest a role for MyD88-dependent pathways in
      induction of IP-10 and IFN-beta during chlamydial infection. Furthermore,
      treatment of infected macrophages with an endosomal maturation inhibitor
      significantly reduced chlamydial-induced IFN-beta. Because endosomal maturation
      is required for MyD88-dependent intracellular pathogen recognition receptors to
      function, our data suggest a role for the intracellular pathogen recognition
      receptor(s) in induction of IFN-beta and IP-10 during chlamydial infection.
      Furthermore, the intracellular pathways that lead to chlamydial-induced IFN-beta
      function through TANK-binding kinase mediated phosphorylation and nuclear
      translocation of IFN regulatory factor-3.

PMID- 15972680
TI  - Endotoxin tolerance disrupts chromatin remodeling and NF-kappaB transactivation
      at the IL-1beta promoter.
AB  - The NF-kappaB family plays a crucial role in the pathogenesis of highly lethal
      septicemia by modulating transcription of many innate and adaptive immunity
      genes. Two phases of NF-kappaB activation occur: cytosolic activation and nuclear
      transactivation. Septicemia with multiorgan failure is associated with chronic
      activation of cytosolic NF-kappaB with translocation and accumulation of
      increased levels of nuclear p65 in blood leukocytes. Paradoxically, NF-kappaB
      dependent transcription of many proinflammatory genes responding to bacterial LPS
      endotoxin (LPS) is persistently repressed during septicemia; this phenomenon of
      LPS tolerance is associated with immunosuppression and poor prognosis. This
      report suggests an explanation for this paradox. Using an in vitro human
      leukocyte model and chromatin immunoprecipitation assays, we find that both the
      cytosolic activation and nuclear transactivation phases of NF-kappaB occur in LPS
      responsive THP-1 promonocytes with recruitment and binding of NF-kappaB p65 at
      the IL-1beta promoter. However, transcriptionally repressed LPS-tolerant THP-1
      cells do not bind NF-kappaB p65 at the IL-1beta promoter, despite cytosolic
      activation and accumulation of p65 in the nucleus. In contrast, NF-kappaB p50,
      which also accumulates in the nucleus, constitutively binds to the IL-1beta
      promoter NF-kappaB site in both LPS-responsive and LPS-tolerant cells. The level
      of p65 binding correlates with a binary shift in nucleosome remodeling between
      histone H3 phosphorylation at serine 10 and methylation of histone H3 at lysine
      9. We conclude that LPS tolerance disrupts the transactivating stage of NF-kappaB
      p65 and altered nucleosome remodeling at the IL-1beta promoter in human
      leukocytes.

PMID- 15972681
TI  - ERK activation following macrophage FcgammaR ligation leads to chromatin
      modifications at the IL-10 locus.
AB  - We have previously demonstrated that macrophages stimulated in the presence of
      immune complexes produce high levels of IL-10. We now examine the mechanism of IL
      10 superinduction. We report that the enhanced production of IL-10 correlates
      with a rapid and enhanced activation of two MAPKs, ERK and p38. The inhibition of
      either ERK or p38 prevented IL-10 induction, indicating that both MAPKs were
      required for IL-10 synthesis. By chromatin immunoprecipitation assay, we
      demonstrate that activation of ERK leads to the phosphorylation of serine 10 on
      histone H3 at the il-10 gene, making the promoter more accessible to
      transcription factors generated in response to p38 activation. Inhibition of ERK
      activation prevented histone modifications, and decreased the binding of Sp1 and
      STAT3 to the IL-10 promoter. We conclude that the activation of ERK following
      FcgammaR ligation leads to a remodeling of the chromatin at the il-10 locus,
      making it more accessible to transcription factors. The rapid and transient
      regulation of transcription factor accessibility to the IL-10 promoter by MAPK
      activation represents a novel way that the production of this cytokine is
      regulated.

PMID- 15972682
TI  - beta2-Adrenoceptor agonists, like glucocorticoids, repress eotaxin gene
      transcription by selective inhibition of histone H4 acetylation.
AB  - Eotaxin is a potent eosinophil chemoattractant implicated in various allergic
      inflammatory conditions including asthma, but relatively little is known about
      its regulation. Human airway smooth muscle cells are an important source of
      eotaxin in the airway. We have previously demonstrated that beta(2)-adrenoceptor
      agonists (beta(2)-agonists) and glucocorticoids additively inhibit eotaxin
      production in human airway smooth muscle cells, but the underlying mechanisms are
      unclear. Here, we studied the molecular mechanisms of their actions and
      interactions on eotaxin gene transcription. TNF-alpha-induced eotaxin gene
      transcription was mediated mainly by the transcription factor NF-kappaB (p65/p50)
      as analyzed by luciferase reporter gene assay, Western blotting, EMSA, and
      electrophoretic mobility supershift assay. Chromatin immunoprecipitation assay
      demonstrated that TNF-alpha also induced selective histone H4 acetylation on
      lysines 5 and 12 at the eotaxin promoter site and p65 binding to the eotaxin
      promoter, resulting in eotaxin gene transcription. The inhibition of eotaxin
      production by beta(2)-agonists and glucocorticoids was transcriptional and not
      due to altered NF-kappaB nuclear translocation or in vitro promoter binding
      capability, but due to their inhibition of TNF-alpha-induced histone H4
      acetylation and p65 in vivo binding to the promoter. Additive inhibition was
      achieved when the two groups of drugs were combined. Our findings reveal a novel
      mechanism by which beta(2)-agonists, like glucocorticoids, regulate NF-kappaB
      mediated inflammatory gene expression through inhibition of histone acetylation.
      This provides one explanation for the benefits that result when these agents are
      combined to treat asthma, and may have important implications in a wide range of
      inflammatory diseases.

PMID- 15972683
TI  - Neutrophil-mediated maturation of chemerin: a link between innate and adaptive
      immunity.
AB  - Dendritic cells and macrophages are professional APCs that play a central role in
      initiating immune responses, linking innate and adaptive immunity. Chemerin is a
      novel chemoattractant factor that specifically attracts APCs through its receptor
      ChemR23. Interestingly, chemerin is secreted as a precursor of low biological
      activity, prochemerin, which upon proteolytic removal of a C-terminal peptide, is
      converted into a potent and highly specific agonist of its receptor. Given the
      fact that APCs are often preceded by polymorphonuclear cells (PMN) in
      inflammatory infiltrates, we hypothesized that PMN could mediate chemerin
      generation. We demonstrate here that human degranulated PMNs release proteases
      that efficiently convert prochemerin into active chemerin. The use of specific
      protease inhibitors allowed us to identify the neutrophil serine proteases
      cathepsin G and elastase as responsible for this process. Mass spectrometry
      analysis of processed prochemerin showed that each protease generates
      specifically a distinct form of active chemerin, differing in their C terminus
      and initially identified in human inflammatory fluids. These findings strongly
      suggest that bioactive chemerin generation takes place during the early stages of
      inflammation, underscoring the functional contribution of chemerin as a bridge
      between innate and adaptive immunity.

PMID- 15972684
TI  - Differential involvement of BB loops of toll-IL-1 resistance (TIR) domain
      containing adapter proteins in TLR4- versus TLR2-mediated signal transduction.
AB  - TLRs sense pathogens and transmit intracellular signals via the use of specific
      adapter proteins. We designed a set of "blocking peptides" (BPs) comprised of the
      14 aa that correspond to the sequences of the BB loops of the four known Toll-IL
      1 resistance (TIR) domain-containing adapter proteins (i.e., MyD88, TIR domain
      containing adapter inducing IFN-beta (TRIF), TRIF-related adapter molecule
      (TRAM), and TIR-domain containing adapter protein (TIRAP)) linked to the cell
      penetrating segment of the antennapedia homeodomain. LPS (TLR4)-mediated gene
      expression, as well as MAPK and transcription factor activation associated with
      both MyD88-dependent and -independent signaling pathways, were disrupted by all
      four BPs (TRAM approximately MyD88 > TRIF > TIRAP), but not by a control peptide.
      In contrast, none of the BPs inhibited TLR2-mediated activation of MAPKs. Only
      the MyD88 BP significantly blocked Pam3Cys-induced IL-1beta mRNA; however, the
      inhibitory effect was much less than observed for LPS. Our data suggest that the
      interactions required for a fully functional TLR4 signaling "platform" are
      disrupted by these BPs, and that the adapter BB loops may serve distinct roles in
      TLR4 and TLR2 signalosome assembly.

PMID- 15972685
TI  - Oxidized phospholipids negatively regulate dendritic cell maturation induced by
      TLRs and CD40.
AB  - Maturation of dendritic cells (DCs) induced by pathogen-derived signals via TLRs
      is a crucial step in the initiation of an adaptive immune response and therefore
      has to be well controlled. In this study, we demonstrate that oxidized
      phospholipids (ox-PLs), which are generated during infections, apoptosis, and
      tissue damage, interfere with DC activation, preventing their maturation. ox-PLs
      blocked TLR-3- and TLR-4-mediated induction of the costimulatory molecules CD40,
      CD80, CD83, and CD86, the cytokines IL-12 and TNF, as well as lymphocyte
      stimulatory capacity. CD40 and TLR-2-mediated cytokine production was also
      inhibited, whereas up-regulation of costimulatory molecules via these receptors
      was not affected by ox-PLs. Thus, formation of ox-PLs during the course of an
      inflammatory response may represent a negative-feedback loop preventing excessive
      and sustained immune reactions through regulating DC maturation.

PMID- 15972686
TI  - Application of plasmid DNA encoding IL-18 diminishes development of herpetic
      stromal keratitis by antiangiogenic effects.
AB  - HSV-1 infection of the eye can cause a blinding immunoinflammatory stromal
      keratitis (SK) lesion. Using the mouse model, we have demonstrated that
      angiogenesis is an essential step in lesion pathogenesis because its inhibition
      results in diminished severity. The molecules involved in causing corneal
      angiogenesis are multiple and include the vascular endothelial growth factor
      (VEGF) family of proteins. In this report we show that application of plasmid DNA
      encoding IL-18 to the cornea of mice before HSV-1 ocular infection resulted in
      reduced angiogenesis and diminished SK immunoinflammatory lesions. The
      antiangiogenic effects of IL-18 treatment appeared to be mediated by inhibition
      of VEGF production in the cornea. We also showed that IL-18 controlled VEGF
      expression in vitro and also decreased CpG oligodeoxynucleotide induced VEGF
      dependent neovascularization. In addition the administration of IL-18-binding
      protein, an IL-18 antagonist, into the inflammatory eye resulted in elevated
      angiogenesis and increased VEGF expression. Our results indicate that IL-18 is an
      important endogenous negative regulator of HSV-induced angiogenesis resulting in
      reduced SK lesion severity. Our results could mean that IL-18 administration may
      represent a useful approach to manage unwanted angiogenesis.

PMID- 15972687
TI  - Extracellular cyclophilins contribute to the regulation of inflammatory
      responses.
AB  - The main regulators of leukocyte trafficking during inflammatory responses are
      chemokines. However, another class of recently identified chemotactic agents is
      extracellular cyclophilins, the proteins mostly known as receptors for the
      immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte
      chemotaxis in vitro and have been detected at elevated levels in inflamed
      tissues, suggesting that they might contribute to inflammatory responses. We
      recently identified CD147 as the main signaling receptor for cyclophilin A. In
      the current study we examined the contribution of cyclophilin-CD147 interactions
      to inflammatory responses in vivo using a mouse model of acute lung injury.
      Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab)
      or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue
      neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These
      findings are the first to demonstrate the significant contribution of
      cyclophilins to inflammatory responses and provide a potentially novel approach
      for reducing inflammation-mediated diseases.

PMID- 15972688
TI  - Transcriptional regulatory functions of heterogeneous nuclear ribonucleoprotein-U
      and -A/B in endotoxin-mediated macrophage expression of osteopontin.
AB  - Osteopontin (OPN) is a highly hydrophilic and negatively charged sialoprotein of
      approximately 298 amino acids with diverse regulatory functions, including cell
      adhesion and migration, tumor growth and metastasis, atherosclerosis, aortic
      valve calcification, and repair of myocardial injury. OPN is unique as an
      endogenous negative feedback inhibitor of NO expression. However, the specific
      cis- and trans-regulatory elements that determine the extent of endotoxin (LPS)-
      and NO-mediated induction of OPN synthesis are unknown. We have previously shown
      that LPS-induced S-nitrosylation of heterogeneous nuclear ribonucleoprotein
      (hnRNP)-A/B inhibits its activity as a constitutive trans-repressor of the OPN
      transcription by significantly decreasing its DNA binding activity. hnRNPs were
      originally described as chromatin-associated RNA-binding proteins that form
      complexes with RNA polymerase II transcripts. The hnRNP family is comprised of
      >20 proteins that contribute to the complex around nascent pre-mRNA and are thus
      able to modulate RNA processing. In this subsequent study, again using RAW 264.7
      murine macrophages and COS-1 cells, we demonstrate that hnRNP-A/B and hnRNP-U
      proteins serve antagonistic transcriptional regulatory functions for OPN
      expression in the setting of LPS-stimulated NO synthesis. In the presence of NO,
      hnRNP-A/B dissociates from its OPN promoter site with subsequent derepression of
      OPN promoter activity. Subsequently, hnRNP-U binds to the same site to further
      augment OPN promoter activation. This has not been previously described for the
      hnRNP proteins. Our results represent a unique transcriptional regulatory
      mechanism which involves interplay between members of the hnRNP protein family.

PMID- 15972689
TI  - TNF-related activation-induced cytokine enhances leukocyte adhesiveness:
      induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein
      kinase C-dependent NF-kappaB activation in endothelial cells.
AB  - Inflammation is a basic pathological mechanism leading to a variety of vascular
      diseases. The inflammatory reaction involves complex interactions between both
      circulating and resident leukocytes and the vascular endothelium. In this study,
      we report evidence for a novel action of TNF-related activation-induced cytokine
      (TRANCE) as an inflammatory mediator and its underlying signaling mechanism in
      the vascular wall. TRANCE significantly increased endothelial-leukocyte cell
      interactions, and this effect was associated with increased expression of the
      cell adhesion molecules, ICAM-1 and VCAM-1, on the endothelial cells. RT-PCR
      analysis and promoter assays revealed that expression of these cell adhesion
      molecules was transcriptionally regulated mainly by activation of the
      inflammatory transcription factor, NF-kappaB. TRANCE induced IkappaB-alpha
      phosphorylation and NF-kappaB activation via a cascade of reactions involving the
      TNFR-associated factors, phospholipase C, PI3K, and protein kinase C (PKC-alpha
      and PKC-zeta). It also led to the production of reactive oxygen species via PKC-
      and PI3K-dependent activation of NADPH oxidase in the endothelial cells, and
      antioxidants suppressed the responses to TRANCE. These results demonstrate that
      TRANCE has an inflammatory action and may play a role in the pathogenesis of
      inflammation-related diseases.

PMID- 15972690
TI  - Mannose-binding lectin is a regulator of inflammation that accompanies myocardial
      ischemia and reperfusion injury.
AB  - The mannose-binding lectin (MBL), a circulating pattern recognition molecule,
      recognizes a wide range of infectious agents with resultant initiation of the
      complement cascade in an Ab-independent manner. MBL recognizes infectious non
      self and altered self in the guise of apoptotic and necrotic cells. In this
      study, we demonstrate that mice lacking MBL, and hence are devoid of MBL
      dependent lectin pathway activation but have fully active alternative and
      classical complement pathways, are protected from cardiac reperfusion injury with
      resultant preservation of cardiac function. Significantly, mice that lack a major
      component of the classical complement pathway initiation complex (C1q) but have
      an intact MBL complement pathway, are not protected from injury. These results
      suggest that the MBL-dependent pathway of complement activation is a key
      regulator of myocardial reperfusion ischemic injury. MBL is an example of a
      pattern recognition molecule that plays a dual role in modifying inflammatory
      responses to sterile and infectious injury.

PMID- 15972691
TI  - Global analysis of Smad2/3-dependent TGF-beta signaling in living mice reveals
      prominent tissue-specific responses to injury.
AB  - Smad2 and Smad3 (Smad2/3) proteins are key signaling molecules for TGF-beta and
      some related family members regulating the transcription of several hundred
      genes. TGF-beta have key roles in development, tissue homeostasis, and the
      pathogenesis of many human diseases, including cancer, fibrotic disorders,
      developmental defects, and neurodegeneration. To study the temporal and spatial
      patterns of Smad2/3-dependent signaling in normal and pathological conditions in
      the living organism, we engineered transgenic mice with a Smad-responsive
      luciferase reporter construct (SBE-luc mice). Using bioluminescent imaging, we
      assessed Smad2/3 signaling activity noninvasively in living mice. At baseline,
      this activity was highest in brain, intestine, heart, and skin, and correlated
      with biochemical measurements of reporter activity. Primary astrocytes cultured
      from SBE-luc mice showed specific activation of the reporter in response to
      Smad2/3-activating TGF-beta family members. Treatment of mice with the endotoxin
      LPS resulted in a fast and vigorous, but transient activation of the reporter in
      the intestine. Although the response was similarly rapid in brain, it remained
      increased, indicating important but different cellular responses to endotoxin
      challenge in these organs. Traumatic brain injury with a needle stab resulted in
      local activation of Smad2/3-dependent genes and a severalfold increase in
      bioluminescence in living mice. SBE-luc mice can therefore be used to study
      temporal, tissue-specific activation of Smad2/3-dependent signaling in living
      mice in normal or pathological conditions as well as for the identification of
      endogenous or synthetic modulators of this pathway.

PMID- 15972692
TI  - Modulation of orphan nuclear receptor NURR1 expression by methotrexate in human
      inflammatory joint disease involves adenosine A2A receptor-mediated responses.
AB  - Modulation by proinflammatory mediators indicate that NURR1 induction represents
      a point of convergence of distinct signaling pathways, suggesting an important
      common role for this transcription factor in mediating multiple inflammatory
      signals. The present study identifies NURR1 as a molecular target of methotrexate
      (MTX) action in human inflammatory joint disease and examines the mechanism
      through which MTX modulates NURR1 expression. MTX significantly suppresses
      expression of NURR1 in vivo in patients with active psoriatic arthritis (n = 10;
      p < 0.002) who were prescribed low-dose MTX for management of peripheral
      arthritis. Importantly, reduction in NURR1 levels correlate (n = 10; r = 0.57; p
      = 0.009) with changes in disease activity score (both clinical and laboratory
      parameters). MTX selectively modulates NURR1 levels induced by inflammatory
      stimuli and growth factors in resident cell populations of synovial tissue. In
      primary human synoviocytes and microvascular endothelial cells, we observe dose
      dependent differential effects of MTX on steady-state and inducible NURR1 levels.
      Our data confirms that adenosine, and its stable analog 5'-N
      ethylcarboxamideadenosine, can mimic the differential effects of MTX on NURR1
      transcription. In addition, we verify that the inhibitory effect of low-dose MTX
      on NURR1 activation is mediated through the adenosine receptor A2. More
      specifically, our data distinguishes the selective involvement of the A2A
      receptor subtype in these responses. In summary, these findings establish the
      nuclear orphan receptor NURR1 as a molecular target of MTX action in human
      inflammatory joint disease and demonstrate that the immunomodulatory actions of
      MTX on NURR1 expression are mediated through adenosine release.

PMID- 15972694
TI  - X chromosome monosomy: a common mechanism for autoimmune diseases.
AB  - The majority of human autoimmune diseases are characterized by female
      predominance. Although sex hormone influences have been suggested to explain this
      phenomenon, the mechanism remains unclear. In contrast to the role of hormones,
      it has been suggested, based on pilot data in primary biliary cirrhosis, that
      there is an elevation of monosomy X in autoimmune disease. Using peripheral white
      blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease
      (AITD), or healthy age-matched control women, we studied the presence of monosomy
      X rates using fluorescence in situ hybridization. We also performed dual-color
      fluorescence in situ hybridization analysis with a chromosome Y alpha-satellite
      probe to determine the presence of the Y chromosome in the monosomic cells. In
      subsets of patients and controls, we determined X monosomy rates in white blood
      cell subpopulations. The rates of monosomy X increased with age in all three
      populations. However, the rate of monosomy X was significantly higher in patients
      with SSc and AITD when compared with healthy women (6.2 +/- 0.3% and 4.3 +/-
      0.3%, respectively, vs 2.9 +/- 0.2% in healthy women, p < 0.0001 in both
      comparisons). Importantly, X monosomy rate was more frequent in peripheral T and
      B lymphocytes than in the other blood cell populations, and there was no evidence
      for the presence of male fetal microchimerism. These data highlight the thesis
      that chromosome instability is common to women with SSc and AITD and that
      haploinsufficiency for X-linked genes may be a critical factor for the female
      predominance of autoimmune diseases.

PMID- 15972693
TI  - 5-aminoimidazole-4-carboxamide ribonucleoside: a novel immunomodulator with
      therapeutic efficacy in experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis, is a Th1-mediated inflammatory demyelinating disease of the CNS. AMP
      activated protein kinase was reported recently to have anti-inflammatory
      activities by negatively regulating NF-kappaB signaling. In this study, we
      investigated the prophylactic and therapeutic efficacy of an AMP-activated
      protein kinase activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR),
      in active and passive EAE induced by active immunization with PLP(139-151) or
      MOG(35-55) and in adoptive transfer of PLP(139-151)-sensitized T cells,
      respectively. In vivo treatment with AICAR exerted both prophylactic and
      therapeutic effects on EAE, attenuating the severity of clinical disease. The
      anti-inflammatory effects of AICAR were associated with the inhibition of the Ag
      specific recall responses and inhibition of the Th1-type cytokines IFN-gamma and
      TNF-alpha, whereas it induced the production of Th2 cytokines IL-4 and IL-10.
      Treatment of PLP(139-151)-specific T cells in vitro with AICAR decreased their
      expression of T-bet in response to IL-12, a Th1 transcription factor, whereas in
      response to IL-4, it induced the expression and phosphorylation of Th2
      transcription factors GATA3 and STAT6, respectively. Moreover, treatment of APCs
      in vitro with AICAR inhibited their capability to present the proteolipid protein
      peptide to PLP(139-151)-specific T cells. In an irrelevant Th1-mediated, OT-2 TCR
      transgenic mouse model, AICAR impaired in vivo Ag-specific expansion of CD4(+) T
      cells. Together, these findings show for the first time that AICAR is a novel
      immunomodulator with promising beneficial effects for the treatment of multiple
      sclerosis and other Th1-mediated inflammatory diseases.

PMID- 15972695
TI  - The clinical benefit of adjunctive dexamethasone in tuberculous meningitis is not
      associated with measurable attenuation of peripheral or local immune responses.
AB  - Outcome from tuberculous meningitis (TBM) is believed to be dependent on the
      severity of the intracerebral inflammatory response. We have recently shown that
      dexamethasone improved survival in adults with TBM and postulated that the
      clinical effect would be associated with a measurable systemic and intracerebral
      impact on immunological markers of inflammation. Prolonged inflammatory responses
      were detected in all TBM patients irrespective of treatment assignment (placebo
      or dexamethasone). The inflammatory response in the cerebrospinal fluid was
      characterized by a leukocytosis (predominantly CD3(+)CD4(+) T lymphocytes,
      phenotypically distinct from those in the peripheral blood), elevated
      concentrations of inflammatory and anti-inflammatory cytokines, chemokines, and
      evidence of prolonged blood-brain barrier dysfunction. Dexamethasone
      significantly modulated acute cerebrospinal fluid protein concentrations and
      marginally reduced IFN-gamma concentrations; other immunological and routine
      biochemical indices of inflammation were unaffected. Peripheral blood monocyte
      and T cell responses to Mycobacterium tuberculosis Ags were also unaffected.
      Dexamethasone does not appear to improve survival from TBM by attenuating
      immunological mediators of inflammation in the subarachnoid space or by
      suppressing peripheral T cell responses to mycobacterial Ags. These findings
      challenge previously held theories of corticosteroid action in this disease. An
      understanding of how dexamethasone acts in TBM may suggest novel and more
      effective treatment strategies.

PMID- 15972696
TI  - Response of memory CD8+ T cells to severe acute respiratory syndrome (SARS)
      coronavirus in recovered SARS patients and healthy individuals.
AB  - To date, the pathogenesis of severe acute respiratory syndrome (SARS) in humans
      is still not well understood. SARS coronavirus (SARS-CoV)-specific CTL responses,
      in particular their magnitude and duration of postinfection immunity, have not
      been extensively studied. In this study, we found that heat-inactivated SARS-CoV
      elicited recall CTL responses to newly identified spike protein-derived epitopes
      (SSp-1, S978, and S1202) in peripheral blood of all HLA-A*0201(+) recovered SARS
      patients over 1 year postinfection. Intriguingly, heat-inactivated SARS-CoV
      elicited recall-like CTL responses to SSp-1 but not to S978, S1202, or dominant
      epitopes from several other human viruses in 5 of 36 (13.8%) HLA-A*0201(+)
      healthy donors without any contact history with SARS-CoV. SSp-1-specific CTLs
      expanded from memory T cells of both recovered SARS patients, and the five
      exceptional healthy donors shared a differentiated effector CTL phenotype,
      CD45RA(+)CCR7(-)CD62L(-), and expressed CCR5 and CD44. However, compared with the
      high avidity of SSp-1-specific CTLs derived from memory T cells of recovered SARS
      patients, SSp-1-specific CTLs from the five exceptional healthy donors were of
      low avidity, as determined by their rapid tetramer dissociation kinetics and
      reduced cytotoxic reactivity, IFN-gamma secretion, and intracellular production
      of IFN-gamma, TNF-alpha, perforin, and granzyme A. These results indicate that
      SARS-CoV infection induces strong and long-lasting CTL-mediated immunity in
      surviving SARS patients, and that cross-reactive memory T cells to SARS-CoV may
      exist in the T cell repertoire of a small subset of healthy individuals and can
      be reactivated by SARS-CoV infection.

PMID- 15972697
TI  - Novel protein and poxvirus-based vaccine combinations for simultaneous induction
      of humoral and cell-mediated immunity.
AB  - The presence of both cell-mediated and humoral immunity is important in
      protection from and clearance of a number of infectious pathogens. We describe
      novel vaccine regimens using combinations of plasmid DNA, poxvirus and protein to
      induce strong Ag-specific T cell and Ab responses simultaneously in a murine
      model. Intramuscular (i.m.) immunization with plasmid DNA encoding the middle Ag
      of hepatitis B (DNA) concurrently with a commercial hepatitis B virus (HBV)
      vaccine (Engerix-B) followed by boosting immunizations with both modified
      vaccinia virus Ankara (MVA) encoding the middle Ag of HBV and Engerix-B induced
      high levels of CD4(+) and CD8(+) T cells and high titer Ab responses to hepatitis
      B surface Ag (HbsAg). Substitution of Engerix-B with adjuvant-free rHBsAg induced
      similar T cell responses and greatly enhanced Ab levels. Repeated immunizations
      with recombinant or nonrecombinant MVA mixed with Ag induced higher titers of Abs
      compared with immunization with either Ag or Engerix-B further demonstrating this
      novel adjuvant effect of MVA. The poxviruses NYVAC, fowlpox (FP9) and ALVAC, and
      to a lesser extent, adenovirus, also displayed similar adjuvant properties when
      used in combination with rHBsAg. The use of poxviruses as an adjuvant for protein
      to concurrently induce Ag-specific T cells and Abs could be applied to the
      development of vaccines for many diseases, including HIV and malaria, where both
      cell mediated and humoral immunity may be important for protection.

PMID- 15972699
TI  - Oxygen sensing: getting pumped by sterols.
AB  - Oxygen plays a pivotal role in the maintenance of life for all eukaryotes, with
      the exception of strict anaerobes. Eukaryotes have developed mechanisms to sense
      and respond to decreased oxygen levels. How eukaryotes sense oxygen is still not
      fully understood. What is (or are) the oxygen sensor(s)? This question has vital
      physiological and pathophysiological implications, because all living aerobic
      organisms have adaptive mechanisms to maintain oxygen homeostasis. A recent
      report describes a novel eukaryotic oxygen-sensing mechanism in the fission yeast
      Schizosaccharomyces pombe, involving the depletion of sterols as a trigger to
      induce gene expression in response to decreased oxygen levels. It is not yet
      clear whether this mechanism is involved in the mammalian response to hypoxia,
      possibly in conjunction with activation of one or both of the hypoxia-inducible
      factor (HIF-1 or HIF-2) transcription factors.

PMID- 15972698
TI  - A Rab-E GTPase mutant acts downstream of the Rab-D subclass in biosynthetic
      membrane traffic to the plasma membrane in tobacco leaf epidermis.
AB  - The function of the Rab-E subclass of plant Rab GTPases in membrane traffic was
      investigated using a dominant-inhibitory mutant (RAB-E1(d)[NI]) of Arabidopsis
      thaliana RAB-E1(d) and in vivo imaging approaches that have been used to
      characterize similar mutants in the plant Rab-D2 and Rab-F2 subclasses. RAB
      E1(d)[NI] inhibited the transport of a secreted green fluorescent protein marker,
      secGFP, but in contrast with dominant-inhibitory RAB-D2 or RAB-F2 mutants, it did
      not affect the transport of Golgi or vacuolar markers. Quantitative imaging
      revealed that RAB-E1(d)[NI] caused less intracellular secGFP accumulation than
      RAB-D2(a)[NI], a dominant-inhibitory mutant of a member of the Arabidopsis Rab-D2
      subclass. Furthermore, whereas RAB-D2(a)[NI] caused secGFP to accumulate
      exclusively in the endoplasmic reticulum, RAB-E1(d)[NI] caused secGFP to
      accumulate additionally in the Golgi apparatus and a prevacuolar compartment that
      could be labeled by FM4-64 and yellow fluorescent protein (YFP)-tagged
      Arabidopsis RAB-F2(b). Using the vacuolar protease inhibitor E64-d, it was shown
      that some secGFP was transported to the vacuole in control cells and in the
      presence of RAB-E1(d)[NI]. Consistent with the hypothesis that secGFP carries a
      weak vacuolar-sorting determinant, it was shown that a secreted form of DsRed
      reaches the apoplast without appearing in the prevacuolar compartment. When fused
      to RAB-E1(d), YFP was targeted specifically to the Golgi via a saturable
      nucleotide- and prenylation-dependent mechanism but was never observed on the
      prevacuolar compartment. We propose that RAB-E1(d)[NI] inhibits the secretory
      pathway at or after the Golgi, causing an accumulation of secGFP in the upstream
      compartments and an increase in the quantity of secGFP that enters the vacuolar
      pathway.

PMID- 15972700
TI  - A moving new role for the sodium pump in epithelial cells and carcinomas.
AB  - The Na,K-ATPase, or sodium pump, is a ubiquitous plasma membrane protein in
      higher eukaryotes, including humans, that carries out the coupled active
      transport of Na+ ions out of the cell and of K+ ions into the cell, using the
      energy of hydrolysis of adenosine triphosphate. In recent years, it has been
      suggested that that this protein may also be involved in various other functions,
      such as transducing information from the extracellular milieu to intracellular
      signaling pathways, much like a growth factor receptor. It has also been
      suggested that the sodium pump may be essential to the formation and function of
      junctional complexes in epithelial cells, and, most recently, it has been shown
      to play a role in epithelial cell motility. Maloney sarcoma virus-transformed
      Madin Darby canine kidney cells have depressed Na,K-ATPase beta subunit abundance
      and enhanced motility as compared with untransformed cells. Repletion of Na,K
      ATPase beta subunits in the transformed cells results in suppression of motility.
      The most recent work, discussed here, demonstrates that the Na,K-ATPase alpha and
      beta subunits play distinct and separate roles, interacting with proteins in the
      phosphatidylinositol 3-kinase pathway and leading to the remodeling of the
      cytoskeleton and lamellipodia formation. The sodium pump subunits thus seem to
      play a role in regulating carcinoma cell motility and may be involved in cell
      motility suppression in many epithelial cells.

PMID- 15972701
TI  - Teaching resources. Nuclear transactivators and repressors.
AB  - This Teaching Resource provides lecture notes and slides for a class covering the
      mechanism and regulation of eukaryotic gene transcription machinery and is part
      of the course "Cell signaling systems: a course for graduate students." This
      lecture begins with an overview of eukaryotic gene transcription and provides
      discussions regarding the current models of mechanisms of transcription by RNA
      polymerase II (Pol II). Recent views on the action of Mediator will also be
      discussed. Finally, a detailed study will be presented to provide evidence for a
      role for enhancer-promoter communication in gene activation.

PMID- 15972702
TI  - Sonographic evaluation of early-stage breast cancers that undergo neoadjuvant
      chemotherapy.
AB  - OBJECTIVE: We prospectively evaluated low-stage breast cancers treated with
      neoadjuvant chemotherapy using whole-volume sonography and color Doppler imaging.
      METHODS: Thirty-four women with breast cancer (mean maximum size, 2.4 cm)
      received neoadjuvant chemotherapy with doxorubicin and docetaxel. Targeted whole
      volume sonography of tumor sites was performed before and after chemotherapy to
      assess mass size, color pixel speed-weighted density, and American College of
      Radiology Breast Imaging Reporting and Data System sonographic characteristics.
      After chemotherapy, tumor sites were excised by lumpectomy or mastectomy.
      RESULTS: Three (11.3%) of 34 patients had a complete histologic response. After
      chemotherapy, correlation was r = 0.716 between final histologic and sonographic
      sizes. Compared with histologic residual tumors, sonography had 4 false-negative
      results, 3 false-positive results, and 27 true-positive results (sensitivity,
      87%), with no false-negative results among a subgroup of tumors of 7 mm and
      larger (sensitivity, 100%). The 3 cases with false-positive results were
      histologic fibrosis or biopsy changes. Mean speed-weighted density was 0.015
      before and 0.0082 after chemotherapy (P = .03). After chemotherapy, vascularity
      was less common within (P = .06) or adjacent to (P = .009) masses or in tumor
      sites (P = .05). Prechemotherapy variables of gray scale characteristics and
      vascularity were compared with final histologic size, and all had P > .20.
      CONCLUSIONS: Postchemotherapy sensitivity of sonography was high for residual
      tumors of 7 mm or larger. Correlation was moderate between histologic and
      sonographic final tumor sizes. False-positive results were caused by fibrosis or
      biopsy-related changes. False-negative results occurred with residual tumor size
      of 6 mm or smaller. After chemotherapy, vascularity usually decreased, and this
      was not specific for complete response. Before chemotherapy, no vascular or gray
      scale feature at initial imaging predicted complete responders.

PMID- 15972703
TI  - Flow pattern and vascular resistive index as predictors of malignancy risk in
      thyroid follicular neoplasms.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether flow pattern and
      resistive index (RI) are useful parameters for distinguishing benign from
      malignant thyroid follicular neoplasms (FNs). METHODS: Eighty-six thyroid nodules
      that underwent sonographically guided fine-needle aspiration and were diagnosed
      as cases of FN were evaluated by power and duplex Doppler sonography. Pathologic
      correlation was available for all nodules. The flow pattern seen via power
      Doppler examination was ranked for each nodule on a scale of 0 to 4, in
      increasing flow order. For each nodule, the RI value was considered the average
      of 1 to 3 values obtained with different flow signals. RESULTS: Ten nodules
      (11.63%) were malignant (3 follicular carcinomas, 5 follicular variants of
      papillary carcinoma, and 2 papillary carcinomas). Fourteen nodules (16.27%) were
      adenomas, and 62 (72%) were non-neoplastic nodules. The average RI in non
      neoplastic nodules was 0.588 (P < .001, chi(2) test): 0.662 in adenomas and 0.763
      in malignant nodules. None of the nodules had flow pattern type 0. Flow patterns
      1 and 2 (peripheral flow only or predominantly) were present in 58 non-neoplastic
      nodules (93.5%), 10 adenomas (71.4%), and 2 malignant nodules (20%). Flow pattern
      type 3 (predominantly central flow) was present in 7 malignant nodules (70%), 4
      adenomas (28.6%), and 4 non-neoplastic nodules (6.5%). Only 1 nodule, a papillary
      carcinoma, had flow pattern type 4 (internal flow only). CONCLUSIONS: In FNs,
      there were significant positive associations between predominantly central flow
      and malignancy and between predominantly peripheral flow and benign disease (P <
      .0001, Fisher exact test). However, power Doppler characteristics could not be
      used to rule out malignancy because 20% of malignant nodules had predominantly
      peripheral flow. For predicting malignancy, an RI cutoff of 0.75 had good
      accuracy, specificity, and negative predictive value but had low sensitivity and
      positive predictive value (respectively, 91%, 97%, 92%, 40%, and 67%). Resistive
      index values in non-neoplastic nodules were lower than in adenomas and malignant
      nodules (P < .001, chi(2) test).

PMID- 15972704
TI  - High-frequency color Doppler ultrasonography of the spermatic cord arteries:
      resistive index variation in a cohort of 51 healthy men.
AB  - OBJECTIVE: The purpose of this study was to determine the normal range of Doppler
      ultrasonographic measurements of spermatic cord arteries in a cohort of healthy
      men. METHODS: The spermatic cord arteries of 51 men were interrogated with color
      Doppler ultrasonography. The resistive index (RI) of each artery was measured for
      the entire cohort; peak systolic and end-diastolic velocity values were obtained
      in a smaller subgroup (n = 31). The artery with the lowest RI was labeled A; the
      other 2 arteries were identified as B and C. RESULTS: Three separate arteries
      were identified within the spermatic cord in all individuals. The median RI
      values for arteries A, B, and C were 0.70 (range, 0.48-0.82), 0.84 (0.67-0.90),
      and 0.84 (0.72-0.92), respectively. One-way analysis of variance showed a
      significant difference between the mean RIs of arteries A and B (P < .0001) and
      arteries A and artery C (P < .0001) but not between B and C (P = .49). Peak
      systolic and end-diastolic velocity values differed significantly between
      arteries A and B (P < .0001) and arteries A and C (P < .0001) but not between B
      and C (P = .31). No age effect was shown for the RI measurements of the cohort.
      CONCLUSIONS: Color Doppler ultrasonography enables the objective quantification
      of Doppler measurements of arteries within the spermatic cord. Knowledge of the
      normal range of Doppler measurements for spermatic cord arteries that supply the
      testes may be a useful adjunct to the assessment of the testes.

PMID- 15972705
TI  - Scrotal sonographic findings in equestrians.
AB  - OBJECTIVE: Sports-related injuries are among the major causes of testicular
      trauma. In this study, we aimed to determine sonographically whether chronic
      urogenital trauma during horse riding increases the prevalence of scrotal
      sonographic abnormalities. To our knowledge, there are no studies in the
      literature that have focused on this topic. METHODS: Group 1 included 26 male
      riders with a mean age +/- SD of 31 +/- 2.9 (range, 26-38) years and with a mean
      riding experience of 5 +/- 2.6 (range, 1-10) years, whereas group 2 included 26
      healthy nonriding men with a mean age of 31 +/- 3.2 (range, 26-41) years. After
      the clinical evaluation, all patients underwent scrotal sonographic examination.
      RESULTS: The prevalence of overall scrotal sonographic abnormalities in group 1
      was significantly higher than that in group 2 (77% versus 38%; P < .05). The
      detected sonographic findings in group 1 were varicocele (46%), hydrocele (19%),
      testicular cyst (4%), epididymal cyst (35%), testicular calcification (19%),
      epididymal calcification (8%), scrotal calculus (8%), and inhomogeneity of
      parenchymal echo texture (4%). However, only varicocele (19%), epididymal cyst
      (19%), testicular calcification (12%), and scrotal calculus (4%) were detected in
      group 2. Between the 2 groups, the difference was significant for varicocele
      prevalence (P < .05) and marginally significant for hydrocele prevalence (P =
      .051). CONCLUSIONS: We recommend scrotal sonographic examination of equestrians
      when they have a palpable mass or related symptoms, the etiology of which was
      found in our study to be closely related to horse riding.

PMID- 15972706
TI  - The syndrome of left isomerism: sonographic findings and outcome in prenatally
      diagnosed cases.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of the prenatal
      diagnosis of left isomerism and to assess possible diagnostic and prognostic
      markers. METHODS: We conducted a retrospective review of all previously
      unpublished cases of left isomerism diagnosed in the prenatal and postnatal
      periods in 2 tertiary referral centers in Germany over 15 years. RESULTS: Among
      34 fetuses, 31 had a correct prenatal diagnosis of left isomerism; 31 had an
      interruption of the inferior vena cava with azygos continuation; 22 had different
      types of viscerocardiac heterotaxy; 13 had heart block; and 28 had cardiac
      defects, with a high prevalence of atrioventricular septal defects (n = 24),
      right outflow tract obstruction (n = 11), double-outlet right ventricles (n = 6),
      and anomalous pulmonary venous return (n = 6). Among the 34 cases, 9 underwent
      termination of pregnancy; 2 fetuses died in utero; 5 children died in the
      neonatal period; and 4 children died in infancy. Only the presence of heart block
      and hydrops was significantly correlated with nonsurvival (P < .05). Fourteen
      children survived, with a mean follow-up +/- SD of 2.9 +/- 2.6 years. Three
      survivors underwent single-ventricle palliation, and 1 had successful
      biventricular repair. Three children were awaiting cardiac repair. The remaining
      7 children had minor or no associated cardiac defects and were doing well.
      CONCLUSIONS: Prenatal diagnosis of left isomerism is feasible, with high
      accuracy. Important diagnostic pointers are viscerocardiac heterotaxy, complex
      cardiac malformations, heart block, and interruption of the inferior vena cava.
      The mortality in fetuses and neonates is high in the presence of heart block and
      hydrops, whereas the cardiac defects influence the long-term outcome.

PMID- 15972707
TI  - Three-dimensional power Doppler ultrasound assessment of the cervix for the
      prediction of successful induction of labor with prostaglandin in prolonged
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine whether 3-dimensional (3D)
      power Doppler ultrasound examination of the cervix can predict the success of
      labor induction with prostaglandin in prolonged pregnancy. METHODS: A prospective
      study was conducted with 36 women undergoing labor induction with prostaglandin
      at 41 gestational weeks 5 days and later. All 36 women underwent a transvaginal 2
      dimensional gray scale ultrasound examination and a 3D power Doppler ultrasound
      examination of the cervix immediately before a planned post-term checkup. The
      analyzed variables were length, anterior-posterior diameter, and width of the
      cervix and any cervical funneling, cervical volume (in cubic centimeters),
      vascularization index, flow index, vascularization flow index, parity, and Bishop
      score. Results were compared among women with start of labor at 12 hours or less
      and more than 12 hours after application of the first prostaglandin suppository
      and among women who had delivery at 24 hours or less and more than 24 hours after
      the start of induction. RESULTS: Sonographically measured cervical length was
      shorter (mean, 1.8 versus 2.4 cm; P = .04), the Bishop score was higher (median,
      5 versus 3; P = .02), and more women were parous (70% versus 37%; P = .05) among
      women who were in labor within 12 hours than in those who were not. The Bishop
      score was higher (median, 4 versus 2; P = .03) and more women were parous (69%
      versus 23%; P = .01) among women who had delivery at 24 hours or less than among
      those who did not. Cervical volume and the results of the 3D power Doppler
      ultrasound examination did not differ among women with different outcomes of
      labor induction. CONCLUSIONS: In women undergoing induction of labor with
      prostaglandin at 41 gestational weeks 5 days or later, sonographic cervical
      length, Bishop score, and parity are related to the success of labor induction,
      whereas cervical volume and the results of the 3D power Doppler examination are
      not.

PMID- 15972708
TI  - Correlation of quantitative heel ultrasonography with central dual-energy X-ray
      absorptiometric bone mineral density in postmenopausal women.
AB  - OBJECTIVES: In this study, we sought the proper cutoff level for quantitative
      ultrasonography (QUS) of the heel in identifying bone mineral density (BMD)
      categories as determined by dual-energy x-ray absorptiometry (DXA) in
      postmenopausal women. METHODS: With the use of DXA, BMD categories of the lumbar
      spine and different areas of the left femur of 420 healthy women according to
      World Health Organization definitions were determined. Quantitative
      ultrasonography of the heel was also performed in each subject. Receiver
      operating characteristic curves were plotted, and sensitivity and specificity of
      QUS to diagnose osteoporosis were examined at different points to identify the
      best cutoff level. The diagnostic agreement between the two techniques in
      identifying osteoporosis was assessed with kappa scores. RESULTS: The kappa
      scores were 0.31 for the lumbar region and 0.5 for the femoral neck region. On
      the receiver operating characteristic study, a score of -1 was found to be the
      appropriate cutoff point for QUS studies, in which the sensitivity of QUS to
      diagnose BMD osteoporosis varied between 78% and 87.5% depending on the site of
      the DXA study. With the proposed cutoff point (-1), sensitivity and specificity
      of QUS in detecting osteoporosis at the lumbar spine were 83.9% and 51%,
      respectively, and at the femoral neck were 84% and 50%, respectively.
      CONCLUSIONS: Insufficient agreement between QUS and DXA led to uncertainty on
      expected BMD in people tested by QUS. The proposed cutoff value could achieve
      higher sensitivity but only by accepting higher rates of false-positive results.

PMID- 15972709
TI  - Doppler sonographic evaluation of cerebral blood flow in anemia resulting from
      chronic renal failure.
AB  - OBJECTIVE: This study was undertaken to describe Doppler sonographic measurement
      of cerebral blood flow in anemia secondary to chronic renal failure and to
      compare the results with data gathered from healthy control subjects. We also
      aimed to compare vertebral and internal carotid artery blood flows to see whether
      any alteration of dominance in cerebral blood supply would occur. METHODS: We
      studied 27 predialytic patients with chronic anemia resulting from chronic renal
      failure and 20 healthy control subjects by means of extracranial Doppler
      sonography. In these patients, blood flows of bilateral internal carotid and
      vertebral arteries were measured, and net vertebral artery, net internal carotid
      artery, and total cerebral blood flows were estimated. Statistical significance
      was observed between groups, and the data were correlated with hemoglobin level.
      Variation of the difference of the Doppler measurements between case and control
      groups by side (left or right) or disease status (patient or control subject) was
      analyzed. RESULTS: From the assessed Doppler parameters, only cerebral blood flow
      and right and net vertebral artery blood flows had a significant difference
      between groups (P < .05) and showed a negative correlation with hemoglobin level.
      Vertebral artery blood flow was found to have significant interactions with
      disease status (P = .009) and side (P = .054). CONCLUSIONS: Right vertebral
      artery blood flow is most prone to increase in chronic anemia of chronic renal
      failure. This effect also appears as increasing net vertebral artery blood flow
      and cerebral blood flow.

PMID- 15972710
TI  - Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph
      nodes.
AB  - OBJECTIVE: The purpose of this study was to determine whether lymphatic channels
      (LCs) and sentinel lymph nodes (SLNs) could be detected on sonographic imaging
      after subcutaneous, submucosal, or parenchymal injections of a sonographic
      contrast agent (ie, lymphosonography) in a variety of anatomic locations in
      several animal models. METHODS: Eight swine, 7 canines, 4 rabbits, and a monkey
      were used for these evaluations. Gray scale pulse inversion harmonic imaging of
      the LCs and the SLNs was performed after subcutaneous (n = 58), submucosal (n =
      14), or parenchymal (n = 8) injections of a tissue-specific sonographic contrast
      agent (Sonazoid; GE Healthcare, Oslo, Norway). In many instances, blue dye was
      injected into the same locations as Sonazoid, and surgical dissection of the SLNs
      and LCs was performed for comparison. Scanning electron microscopy (SEM) of
      contrast-enhanced and control lymph nodes from 2 rabbits was performed to
      determine the mechanism of contrast agent uptake and retention within SLNs.
      RESULTS: After subcutaneous, submucosal, or parenchymal contrast agent
      injections, gray scale pulse inversion harmonic imaging could be used to identify
      the number and location(s) of LCs and SLNs. After subcutaneous, submucosal, or
      parenchymal contrast agent injections, Sonazoid was confined to the SLNs (ie,
      contrast enhancement was not detected in the second-echelon nodes). There was
      good agreement between the results of lymphosonography and blue dye with surgical
      dissection in identifying the regional LCs and SLNs. Scanning electron microscopy
      identified vacuoles representing intact contrast microbubbles within contrast
      enhanced SLN macrophages, which were not present in the control lymph nodes.
      CONCLUSIONS: Lymphosonography can be used to detect lymphatic drainage pathways
      and SLNs in a variety of animal models.

PMID- 15972711
TI  - The effects of Levovist and DD-723 in activating platelets and damaging hepatic
      cells of rats.
AB  - OBJECTIVE: The purpose of this study was to compare platelet activation and
      hepatic cell damage produced by 2 ultrasonographic contrast agents with flow
      cytometric and ultrastructural analysis. METHODS: Suspension samples were made by
      mixing Levovist (SH U508A; Schering AG, Berlin, Germany) or DD-723 (Nycomed;
      Amersham Health, Princeton, NJ) with whole blood. The final concentrations of
      Levovist in citrated whole blood were 0, 15, and 75 mg/mL, and those of DD-723
      were 0, 5, and 50 microL/mL. After exposure to ultrasound in vitro, flow
      cytometric analysis was performed to determine the concentration of the CD62P
      activation-specific antigen. To compare the hepatic cell damage associated with
      these 2 agents, we divided 15 rats into 5 groups as follows: group 1, sham
      operation; group 2, Levovist injection only; group 3, DD-723 injection only;
      group 4, Levovist injection (contrast agent) and ultrasound exposure; and group
      5, DD-723 injection and ultrasound exposure. The ultrasonographic contrast agents
      Levovist and DD-723 were administered through the femoral vein and sonicated
      continuously for the first minute; this was followed by sweeping for 5 minutes 10
      seconds after the contrast agent was injected. The rats were perfused via the
      heart with a fixative solution immediately after the sweeping, and then the liver
      was excised; the specimens were studied with electron and light microscopy.
      RESULTS: The percentage of CD62P-expressing platelets increased in both contrast
      agent-ultrasound exposure groups, and the percentage of CD62P-expressing
      platelets was greater in the Levovist group. We observed vacuolation and round
      deposits in the hepatocytes in both contrast agent-ultrasound exposure groups.
      Microbubbles were observed in the rat Kupffer cells, and a few hepatocytes were
      seen unexpectedly in the DD-723 group but were found in neither the Kupffer cells
      nor the hepatocytes in the Levovist group. CONCLUSIONS: Both contrast agents,
      Levovist and DD-723, produced platelet activation and structural change in the
      rat hepatic cells, but only the microbubbles of DD-723 were taken up by the
      Kupffer cells and a few hepatocytes.

PMID- 15972712
TI  - Time-intensity-based quantification of vascularity with single-level dynamic
      contrast-enhanced ultrasonography: a pilot animal study.
AB  - OBJECTIVE: The purpose of this study was to delineate the hemodynamic features of
      VX2 tumor and perineoplastic liver parenchyma and to evaluate the potential
      usefulness of single-level dynamic ultrasonography in the diagnosis of tumors by
      the analysis of time-intensity curves. METHODS: An in vivo animal model was
      studied using a low mechanical index in conjunction with single-level dynamic
      contrast-enhanced ultrasonography. A sulfur hexafluoride contrast agent (SonoVue;
      Bracco SpA, Milan, Italy) was applied in 8 rabbits by intravenous bolus
      injection. Data were acquired before and after VX2 tumor induction. Corresponding
      parameters of the time-intensity curve were measured using wash-in/wash-out curve
      software. RESULTS: No significant difference was found in the time to
      enhancement, time to peak intensity, peak signal intensity, and enhancement
      duration between liver parenchyma before and after VX2 tumor induction (P > .05).
      The typical enhancement pattern of VX2 tumors was hyperechoic relative to liver
      parenchyma during the early phase and hypoechoic during the later phase. The
      curves obtained in carcinomas revealed an early arrival time and time to peak
      intensity with an irregular and sharp decrease of the intensity signal and a very
      early return to baseline, presenting a much more rapid wash-in and wash-out of
      ultrasonographic contrast agents. There was a significant difference in the time
      to enhancement, time to peak intensity, peak signal intensity, and enhancement
      duration between the VX2 tumors and perineoplastic liver parenchyma (P < .001).
      CONCLUSIONS: Single-level dynamic contrast-enhanced ultrasonography with a low
      mechanical index level could provide real-time and continuous enhanced images and
      fully delineate the typical enhancement pattern of liver tumors. The analysis of
      time-intensity curves may provide useful, complementary, and quantitative
      information. This technique may be useful for the diagnosis of liver tumors,
      especially those showing an atypical enhancement pattern on biphasic helical
      computed tomographic scanning.

PMID- 15972713
TI  - Vibrography during tumor neurosurgery.
AB  - OBJECTIVE: The aim of this study was to determine whether elastography, a
      sonographically based real-time strain imaging method for registering the elastic
      properties of tissue, can be used in brain tumor surgery. METHODS: A modification
      of classic elastography called vibrography was applied in these measurements with
      static compression replaced by low-frequency axial vibration. Twenty patients
      were examined with this technique during brain tumor surgery. A conventional
      sonographic system with a custom-designed radio frequency (RF) interface was
      used. The RF data were digitized with a 50-MHz, 12-bit peripheral component
      interconnect analog/digital converter for real-time or offline processing.
      Sonographic RF data were acquired with a 6.5-MHz endocavity curved array. A
      special applicator equipped with a stepping motor moved the ultrasonic probe and
      produced a low-frequency mechanical vibration of approximately 5 to 10 Hz with a
      vibration amplitude of 0.3 mm. RESULTS: Detection of tumors was possible in 18 of
      20 cases. Brain tissue was normally color coded orange or red. Three major groups
      of tumors with different elastic properties relative to brain tissue could be
      differentiated. In 3 cases, the stiffness of the tumor was identical to that of
      brain tissue, but the tumors were surrounded by a thin yellow border. Six tumors
      displayed higher strain than brain, whereas 7 tumors exhibited lower strain than
      the surrounding cerebrum. Two patients could not be assigned clearly to either of
      these groups. CONCLUSIONS: These findings indicate that vibrography is a feasible
      imaging method for brain tumor surgery and may have numerous potential
      applications in neurosurgery if further improvements are made.

PMID- 15972714
TI  - Sonographic evaluation of penile trauma.
AB  - OBJECTIVE: The purpose of this presentation is to illustrate the normal
      sonographic anatomy of the penis and various imaging manifestations of penile
      trauma. METHODS: Penile trauma cases were collected and reviewed retrospectively
      from our archive. RESULTS: The normal sonographic anatomy of the penis and
      various pathologic conditions of patients with penile trauma are discussed.
      CONCLUSIONS: Sonography (especially with color Doppler sonography) is a useful
      imaging method for evaluating penile anatomy and various pathologic features in
      patients with penile trauma.

PMID- 15972715
TI  - Sonographic evaluation of epididymal malakoplakia.

PMID- 15972716
TI  - Idiopathic granulomatous epididymo-orchitis: sonographic appearance.

PMID- 15972717
TI  - Congenital cardiac left ventricular aneurysm with pericardial effusion: early
      prenatal diagnosis and intervention.

PMID- 15972718
TI  - Sonographic evaluation and diagnosis of postoperative pseudotumor of the back
      with histologic correlation.

PMID- 15972719
TI  - Contrast harmonic sonographically guided radio frequency ablation for spontaneous
      ruptured hepatocellular carcinoma.

PMID- 15972720
TI  - Peripheral arterioportal fistula: demonstration with contrast-enhanced
      sonography.

PMID- 15972721
TI  - Sonographic diagnosis of a tracheal extramedullary plasmacytoma.

PMID- 15972722
TI  - Expression of mutant human cystathionine beta-synthase rescues neonatal lethality
      but not homocystinuria in a mouse model.
AB  - Cystathionine beta-synthase (CBS) deficiency is a recessive genetic disorder in
      humans characterized by elevated levels of total plasma homocysteine (tHcy) and
      frequent thrombosis in humans. The I278T mutation is the most common mutation
      found in human CBS-deficient patients. The T424N mutation was identified as a
      mutation in human CBS that could restore function to I278T in Saccharomyces
      cerevisiae. In this report, we have engineered mice that express human I278T and
      I278T/T424N proteins from a metallotheinein-driven transgene. These transgene
      containing mice were then bred to CBS knockout animals (Cbs-) to generate mice
      that express only human I278T or I278T/T424N protein. Both the I278T and the
      I278T/T424N transgenes are able to entirely rescue the previously described
      neonatal mortality phenotype despite the animals having a mean tHcy of 250
      microm. The transgenic Cbs-/- animals exhibit facial alopecia, have moderate
      liver steatosis and are slightly smaller than heterozygous littermates. In
      contrast to human CBS deficiency, these mice do not exhibit extreme
      methioninemia. The mutant proteins are stable in the liver, kidney and colon, and
      liver extracts have only 2-3% of the CBS enzyme activity found in wild-type mice.
      Surprisingly, the I278T/T424N enzyme had exactly the same activity as the I278T
      enzyme indicating that T424N is unable to suppress I278T in mice. Our results
      show that elevated tHcy per se is not responsible for the neonatal lethality
      observed in Cbs-/- animals and suggests that CBS protein may have a function in
      addition to its role in homocysteine catabolism. These transgenic animals should
      be useful in the study of homocysteine related human disease.

PMID- 15972723
TI  - Altered mRNA splicing of the skeletal muscle ryanodine receptor and
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused
      by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes
      has been reported to contribute to some symptoms of DM1, but the cause of muscle
      weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is
      unknown. Here, we investigated the alternative splicing of mRNAs of two major
      proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal
      variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs
      at the C-terminal were significantly increased in skeletal muscles from DM1
      patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel
      variant of SERCA2 was significantly decreased in DM1 patients. The total amount
      of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their
      proteins in HSA(LR) mice were not significantly different. However, heterologous
      expression of ASI(-) in cultured cells showed decreased affinity for
      [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in
      single-channel recording when compared with wild-type (WT) RyR1. In support of
      this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of
      Ca2+ oscillations during caffeine exposure compared with that observed for
      myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1
      mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle.

PMID- 15972724
TI  - Expression of an LMNA-N195K variant of A-type lamins results in cardiac
      conduction defects and death in mice.
AB  - The nuclear lamina is an approximately 10 nm thick proteinaceous layer underlying
      the inner nuclear membrane. The A-type lamins, nuclear intermediate filament
      proteins encoded by the LMNA gene, are basic components of the nuclear lamina.
      Mutations in LMNA are associated with the laminopathies, congenital diseases
      affecting tissue regeneration and homeostasis. One of these laminopathies
      associated with missense mutations in LMNA is dilated cardiomyopathy with
      conduction system disease (DCM-CD1). To understand how the laminopathies arise
      from different mutations in a single gene, we derived a mouse line by homologous
      recombination expressing the Lmna-N195K variant of the A-type lamins with an
      asparagine-to-lysine substitution at amino acid 195, which causes DCM in humans.
      This mouse line shows characteristics consistent with DCM-CD1. Continuous
      electrocardiographic monitoring of cardiac activity demonstrated that
      LmnaN195K/N195K mice die at an early age due to arrhythmia. By immunofluorescence
      and western analysis, the transcription factor Hf1b/Sp4 and the gap junction
      proteins connexin 40 and connexin 43 were misexpressed and/or mislocalized in
      LmnaN195K/N195K hearts. Desmin staining revealed a loss of organization at
      sarcomeres and intercalated disks. Mutations within the LMNA gene may therefore
      cause cardiomyopathy by disrupting the internal organization of the cardiomyocyte
      and/or altering the expression of transcription factors essential to normal
      cardiac development, aging or function.

PMID- 15972725
TI  - The microcephaly ASPM gene is expressed in proliferating tissues and encodes for
      a mitotic spindle protein.
AB  - The most common cause of primary autosomal recessive microcephaly (MCPH) appears
      to be mutations in the ASPM gene which is involved in the regulation of
      neurogenesis. The predicted gene product contains two putative N-terminal
      calponin-homology (CH) domains and a block of putative calmodulin-binding IQ
      domains common in actin binding cytoskeletal and signaling proteins. Previous
      studies in mouse suggest that ASPM is preferentially expressed in the developing
      brain. Our analyses reveal that ASPM is widely expressed in fetal and adult
      tissues and upregulated in malignant cells. Several alternatively spliced
      variants encoding putative ASPM isoforms with different numbers of IQ motifs were
      identified. The major ASPM transcript contains 81 IQ domains, most of which are
      organized into a higher order repeat (HOR) structure. Another prominent spliced
      form contains an in-frame deletion of exon 18 and encodes 14 IQ domains not
      organized into a HOR. This variant is conserved in mouse. Other spliced variants
      lacking both CH domains and a part of the IQ motifs were also detected,
      suggesting the existence of isoforms with potentially different functions. To
      elucidate the biochemical function of human ASPM, we developed peptide specific
      antibodies to the N- and C-termini of ASPM. In a western analysis of proteins
      from cultured human and mouse cells, the antibodies detected bands with
      mobilities corresponding to the predicted ASPM isoforms. Immunostaining of
      cultured human cells with antibodies revealed that ASPM is localized in the
      spindle poles during mitosis. This finding suggests that MCPH is the consequence
      of an impairment in mitotic spindle regulation in cortical progenitors due to
      mutations in ASPM.

PMID- 15972726
TI  - Altered cell surface expression of human MC1R variant receptor alleles associated
      with red hair and skin cancer risk.
AB  - The human melanocortin-1 receptor gene (MC1R) encodes a G-protein coupled
      receptor that is primarily expressed on melanocytes, where it plays a key role in
      pigmentation regulation. Variant alleles are associated with red hair colour and
      fair skin, known as the RHC phenotype, as well as skin cancer risk. The R151C,
      R160W and D294H alleles, designated 'R', are strongly associated with the RHC
      phenotype and have been proposed to result in loss of function receptors due to
      impaired G-protein coupling. We recently provided evidence that the R151C and
      R160W variants can efficiently couple to G-proteins in response to alpha
      melanocyte stimulating hormone. The possibility that altered cellular
      localization of the R151C and R160W variant receptors could underlie their
      association with RHC was therefore considered. Using immunofluorescence and
      ligand binding studies, we found that melanocytic cells exogenously or
      endogenously expressing MC1R show strong surface localization of the wild-type
      and D294H alleles but markedly reduced cell surface expression of the R151C and
      R160W receptors. In additional exogenous expression studies, the R variant D84E
      and the rare I155T variant, also demonstrated a significant reduction in plasma
      membrane receptor numbers. The V60L, V92M and R163Q weakly associated RHC
      alleles, designated 'r', were expressed with normal or intermediate cell surface
      receptor levels. These results indicate that reduced receptor coupling activity
      may not be the only contributing factor to the genetic association between the
      MC1R variants and the RHC phenotype, with MC1R polymorphisms now linked to a
      change in receptor localization.

PMID- 15972727
TI  - Interindividual variability and parent of origin DNA methylation differences at
      specific human Alu elements.
AB  - We investigated the CpG methylation of 19 specific members of Alu sub-families in
      human DNA isolated from whole blood, using an assay based on methylation
      sensitive restriction endonuclease digestion of genomic DNA and 'hot-stop'
      polymerase chain reaction. We found significant interindividual variability in
      the level of methylation for specific Alu elements among the members of 48 three
      generation families. Surprisingly, some of the elements also displayed
      quantitative parent of origin methylation differences; i.e. the mean level of
      methylation differed significantly when the insertions were transmitted through
      paternal versus maternal meiosis. Bisulfite sequence analysis of individual
      elements at such loci suggests, further, that maternal and paternal elements
      differ in the propensity of particular CpG sites to become unmethylated. Some
      individuals who exhibited high levels of methylation at specific Alu elements
      came from families in which more than one member also exhibited abnormal patterns
      of methylation at the differentially methylated regions of the IGF2/H19 or IGF2R
      loci, suggesting that there may be heritable differences between individuals in
      the fidelity with which allelic DNA methylation differences are established or
      maintained. Quantitative parental origin differences in methylation were
      identified only for Alu elements that lie in sub-telomeric or sub-centromeric
      bands of human chromosomes, whereas those assayed at intermediate positions did
      not exhibit any significant differences. The centromere/telomere restricted
      location of the methylation differences and the fact that none of these
      differences occur in regions of chromosomes known to contain transcriptionally
      imprinted genes suggest that maternal/paternal epigenetic modifications may play
      additional roles in processes other than transcriptional control.

PMID- 15972728
TI  - Response to antibiotics of women with symptoms of urinary tract infection but
      negative dipstick urine test results: double blind randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of antibiotic treatment of women with
      symptoms of urinary tract infection but negative urine dipstick testing. DESIGN:
      Prospective, double blind, randomised, placebo controlled trial. SETTING: Primary
      care, among a randomly selected group of general practitioners in Christchurch,
      New Zealand. PARTICIPANTS: 59 women aged 16-50 years presenting with a history of
      dysuria and frequency in whom a dipstick test of midstream urine was negative for
      both nitrites and leucocytes. Participants with complicated urinary tract
      infection were excluded. INTERVENTION: Trimethoprim 300 mg daily for three days
      or placebo. MAIN OUTCOME MEASURES: Self reported diary of symptoms for seven
      days, recording the presence or absence of individual symptoms each day, followed
      by a structured telephone questionnaire after seven days. The main clinical
      outcome was resolution of dysuria at three and seven days and median time to
      resolution. Secondary outcomes were resolution of other symptoms. RESULTS: The
      median time for resolution of dysuria was three days for trimethoprim compared
      with five days for placebo (P = 0.002). At day 3, five (24%) of patients in the
      treatment group had ongoing dysuria compared with 20 (74%) in the placebo group
      (P = 0.005). This difference persisted until day 7: two patients (10%) in the
      treatment group v 11 (41%) in the placebo group; P = 0.02). The number needed to
      treat was 4. The median duration of constitutional symptoms (feverishness,
      shivers) was reduced by four days. CONCLUSIONS: Although a negative dipstick test
      for leucocytes and nitrites accurately predicted absence of infection when
      standard microbiological definitions were used (negative predictive value 92%),
      it did not predict response to antibiotic treatment. Three days' treatment with
      trimethoprim significantly reduced dysuria in women whose urine dipstick test was
      negative. These results support the practice of empirical antibiotic use guided
      by symptoms. Balancing the competing interests of symptom relief and the
      minimisation of antibiotic use remains a dilemma-further research is needed to
      determine clinical predictors of response to antibiotics.

PMID- 15972729
TI  - Experimental evaluation of a spherical aberration-corrected TEM and STEM.
AB  - We have successfully developed a spherical aberration (Cs)-corrected electron
      microscope for probe- and image-forming systems using hexapole correctors. The
      performance of the microscope has been evaluated experimentally. The point
      resolution attained using the image-forming Cs-corrector is better than 0.12 nm.
      For scanning transmission electron microscopy, the Ronchigram flat area was >40
      mrad in half-angle using the probe-forming Cs-corrector.

PMID- 15972784
TI  - Abstracts of the 9th International Conference on Malignant Lymphoma, June 2005.

PMID- 15972730
TI  - A comparative analysis of radiotherapy use and patient outcome in males and
      females with breast cancer.
AB  - BACKGROUND: The aim was to determine whether gender was a significant prognostic
      factor for post-mastectomy relapse, after accounting for known prognostic factors
      and delivery of radiotherapy. PATIENTS AND METHODS: All patients diagnosed with
      invasive breast cancer between 1 January 1989 and 31 December 1998 who had
      undergone total mastectomy as primary therapy were identified from the British
      Columbia Cancer Agency's Breast Cancer Outcomes Unit database. Patients with pT4
      or M1 disease were excluded. A comparison of patient, tumour and treatment
      factors was made between males and females. Outcomes were analysed in terms of
      locoregional-relapse free survival, breast cancer-specific survival and overall
      survival. RESULTS: Sixty males and 4181 females were identified. Multivariable
      analysis revealed increased tumour size, positive margin status, delivery of
      chemotherapy, positive nodal status and male gender to be significantly
      associated with the use of post-mastectomy radiotherapy. Multivariable analysis
      revealed tumour size, nodal status, tumour grade and presence of vascular space
      invasion to be significantly associated with locoregional recurrence. Gender was
      not a prognostic factor for locoregional recurrence, breast cancer-specific
      survival or overall survival on univariable or multivariable analysis.
      CONCLUSIONS: These data suggest that gender is not a prognostic factor in
      patients undergoing mastectomy for early stage breast cancer. Men having
      mastectomy for breast cancer should receive adjuvant radiotherapy following
      guidelines similar to those developed for females.

PMID- 15972792
TI  - The 5'-AT-rich half-site of Maf recognition element: a functional target for bZIP
      transcription factor Maf.
AB  - The Maf family of proteins are a subgroup of basic region-leucine zipper (bZIP)
      transcription factors, which recognize a long palindromic DNA sequence
      [TGCTGAC(G)TCAGCA] known as the Maf recognition element (MARE). Interestingly,
      the functional target enhancer sequences present in the alphaA-crystallin gene
      contain a well-conserved half-site of MARE rather than the entire palindromic
      sequence. To resolve how Maf proteins bind to target sequences containing only
      MARE half-sites, we examined their binding activities using electrophoretic gel
      mobility shift assays as well as in vitro and in vivo reporter assays. Our
      results indicate that the 5'-flanking region of the MARE half-site is required
      for Maf proteins to bind both in vitro and in vivo. The critical 5'-flanking
      sequences for c-Maf were determined by a selection and amplification binding
      assay and show a preference for AT-rich nucleotides. Furthermore, sequence
      analysis of the regulatory regions of several target genes also suggests that AT
      rich sequences are important. We conclude that Maf can bind to at least two types
      of target sequences, the classical MARE (palindrome type) and a 5'-AT-rich MARE
      half-site (half-site type). Our results provide important new insights into the
      DNA binding and site selection by bZIP transcription factors.

PMID- 15972793
TI  - Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine
      adducts from acetaldehyde.
AB  - Alcoholic beverage consumption is associated with an increased risk of upper
      gastrointestinal cancer. Acetaldehyde (AA), the first metabolite of ethanol, is a
      suspected human carcinogen, but the molecular mechanisms underlying AA
      carcinogenicity are unclear. In this work, we tested the hypothesis that
      polyamines could facilitate the formation of mutagenic alpha-methyl-gamma-hydroxy
      1,N2-propano-2'-deoxyguanosine (Cr-PdG) adducts from biologically relevant AA
      concentrations. We found that Cr-PdG adducts could be formed by reacting
      deoxyguanosine with muM concentrations of AA in the presence of spermidine, but
      not with either AA or spermidine alone. The identities of the Cr-PdG adducts were
      confirmed by both liquid and gas chromatography-mass spectrometry. Using a novel
      isotope-dilution liquid chromatography-mass spectrometry assay, we found that in
      the presence of 5 mM spermidine, AA concentrations of 100 microM and above
      resulted in the formation of Cr-PdG in genomic DNA. These AA levels are within
      the range that occurs in human saliva after alcoholic beverage consumption. We
      also showed that spermidine directly reacts with AA to generate crotonaldehyde
      (CrA), most likely via an enamine aldol condensation mechanism. We propose that
      AA derived from ethanol metabolism is converted to CrA by polyamines in dividing
      cells, forming Cr-PdG adducts, which may be responsible for the carcinogenicity
      of alcoholic beverage consumption.

PMID- 15972794
TI  - PCNA acts as a stationary loading platform for transiently interacting Okazaki
      fragment maturation proteins.
AB  - In DNA replication, the leading strand is synthesized continuously, but lagging
      strand synthesis requires the complex, discontinuous synthesis of Okazaki
      fragments, and their subsequent joining. We have used a combination of in situ
      extraction and dual color photobleaching to compare the dynamic properties of
      three proteins essential for lagging strand synthesis: the polymerase clamp
      proliferating cell nuclear antigen (PCNA) and two proteins that bind to it, DNA
      Ligase I and Fen1. All three proteins are localized at replication foci (RF), but
      in contrast to PCNA, Ligase and Fen1 were readily extracted. Dual photobleaching
      combined with time overlays revealed a rapid exchange of Ligase and Fen1 at RF,
      which is consistent with de novo loading at every Okazaki fragment, while the
      slow recovery of PCNA mostly occurred at adjacent, newly assembled RF. These data
      indicate that PCNA works as a stationary loading platform that is reused for
      multiple Okazaki fragments, while PCNA binding proteins only transiently
      associate and are not stable components of the replication machinery.

PMID- 15972795
TI  - Mapping the interaction of SmpB with ribosomes by footprinting of ribosomal RNA.
AB  - In trans-translation transfer messenger RNA (tmRNA) and small protein B (SmpB)
      rescue ribosomes stalled on truncated or in other ways problematic mRNAs. SmpB
      promotes the binding of tmRNA to the ribosome but there is uncertainty about the
      number of participating SmpB molecules as well as their ribosomal location. Here,
      the interaction of SmpB with ribosomal subunits and ribosomes was studied by
      isolation of SmpB containing complexes followed by chemical modification of
      ribosomal RNA with dimethyl sulfate, kethoxal and hydroxyl radicals. The results
      show that SmpB binds 30S and 50S subunits with 1:1 molar ratios and the 70S
      ribosome with 2:1 molar ratio. SmpB-footprints are similar on subunits and the
      ribosome. In the 30S subunit, SmpB footprints nucleotides that are in the
      vicinity of the P-site facing the E-site, and in the 50S subunit SmpB footprints
      nucleotides that are located below the L7/L12 stalk in the 3D structure of the
      ribosome. Based on these results, we suggest a mechanism where two molecules of
      SmpB interact with tmRNA and the ribosome during trans-translation. The first
      SmpB molecule binds near the factor-binding site on the 50S subunit helping tmRNA
      accommodation on the ribosome, whereas the second SmpB molecule may functionally
      substitute for a missing anticodon stem-loop in tmRNA during later steps of trans
      translation.

PMID- 15972797
TI  - Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic
      prodrugs.
AB  - A CpG-containing DNA oligonucleotide functionalized with the 2-(N-formyl-N
      methyl)aminoethyl thiophosphate protecting group (CpG ODN fma1555) was prepared
      from phosphoramidites 1a-d using solid-phase techniques. The oligonucleotide
      behaved as a prodrug by virtue of its conversion to the well-studied
      immunomodulatory CpG ODN 1555 through thermolytic cleavage of the 2-(N-formyl-N
      methyl)aminoethyl thiophosphate protecting group. Such a conversion occurred at
      37 degrees C with a half-time of 73 h. The immunostimulatory properties of CpG
      ODN fma1555 were evaluated in two in vivo assays, one of which consisted of mice
      challenged in the ear with live Leishmania major metacyclic promastigotes. Local
      intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN
      1555 in reducing the size of Leishmania lesions over time. In a different
      infectious model, CpG ODN 1555 prevented the death of Tacaribe-infected mice (43%
      survival) when administered between day 0 and 3 post infection. Administration of
      CpG ODN fma1555 three days before infection resulted in improved immunoprotection
      (60-70% survival). Moreover, co-administration of CpG ODN fma1555 and CpG ODN
      1555 in this model increased the window for therapeutic treatment against
      Tacaribe virus infection, and thus supports the use of thermolytic
      oligonucleotides as prodrugs in the effective treatment of infectious diseases.

PMID- 15972796
TI  - Matrix metalloproteinase-1 up-regulation by hepatocyte growth factor in human
      dermal fibroblasts via ERK signaling pathway involves Ets1 and Fli1.
AB  - In this study, we clarified the molecular mechanism(s) underlying the regulation
      of matrix metalloproteinase (MMP)-1 gene by hepatocyte growth factor (HGF) in
      cultured human dermal fibroblasts. HGF induced MMP-1 protein as well as mRNA at a
      transcriptional level via extracellular signal-regulated kinase (ERK) signaling
      pathway. The region in the MMP-1 promoter mediating the inducible responsiveness
      to HGF, defined by the transient transfection analysis of the serial 5' deletion
      constructs, contained an Ets binding site. Mutation of this Ets binding site
      abrogated the HGF-inducible promoter activity. Ets1 up-regulated the expression
      of MMP-1 promoter activity, whereas Fli1 had antagonistic effects on them. After
      HGF treatment, the protein level and the binding activity of Ets1 was increased
      and those of Fli1 was decreased, which were canceled by PD98059. These results
      suggest that HGF up-regulates MMP-1 expression via ERK signaling pathway through
      the balance of Ets1 and Fli1, which may be a novel mechanism of regulating MMP-1
      gene expression.

PMID- 15972798
TI  - Comparison of direct (X-ray diffraction and infrared spectrophotometry) and
      indirect (infrared spectrophotometry) methods for the analysis of alpha-quartz in
      airborne dusts.
AB  - In this study, the alpha-quartz contents measured by different analytical
      techniques (X-ray diffraction, direct method; and infrared spectrophotometry,
      direct and indirect methods) were compared. The analyses were carried out on
      filters sampled in an industrial setting by means of a Dorr-Oliver cyclone. To
      verify the methodology used, filters loaded with pure alpha-quartz were also
      analysed. By and large, the agreement between the two direct methods was close on
      average, but on the basis of a comparison of the individual results, considerable
      differences exist. In absolute value, the mean relative deviation between the two
      techniques was <25% in only 47.8% of the cases. The results obtained by the
      indirect method (infrared) were on average 13% lower than the results obtained by
      the two direct methods with a more important difference (23%) for samples where
      calcite was identified by X-ray diffraction in comparison with those where it was
      not (8%). This underestimation, which was not owing to dust losses during
      preparation, is probably explained by the elimination of organic compounds during
      dust calcinations or by the transformation of mineral compounds. The indirect
      method introduces additional sample handling operations with more risk of
      material loss. When the quantity of calcined material was <0.4 mg, the weighing
      operations necessary to correct any losses of material resulted in considerable
      variability. In terms of overall uncertainty, it would be better in this case not
      to carry out correction and to employ an operating mode favouring the recovery of
      a maximum of material while accepting a bias of about 5-7%.

PMID- 15972799
TI  - Phenological variation within and among populations of Plathymenia reticulata in
      Brazilian Cerrado, the Atlantic Forest and transitional sites.
AB  - BACKGROUND AND AIMS: Plathymenia reticulata (Leguminosae) is a Brazilian tree
      that occurs in two biomes: Cerrado, a woody savanna vegetation, and the Atlantic
      Forest, a tropical forest. In this study, phenological patterns and their
      variability within and among populations located in these biomes and in
      transitional zones between them were assessed. METHODS: During a 15-month period,
      individuals from two populations in Cerrado, two in the Atlantic Forest, and six
      in transitional zones (three in a cerrado-like environment and three in forest
      fragments) were evaluated in Minas Gerais State, Brazil. The individuals were
      evaluated monthly according to the proportion of the canopy in each vegetative
      phenophase (leaf fall, leaf flush and mature leaves) and each reproductive
      phenophase (floral buds, flowers, immature fruits and mature fruit/seed
      dispersal). In order to assess the phenological variability within and among
      populations, habitats and biomes, the Shannon-Wiener diversity index, the
      Morisita-Horn similarity index and genetic population approach of partitioning
      diversity were used. KEY RESULTS: Populations of P. reticulata, in general,
      showed similar phenology; the main differences were related to leaf fall, a
      process that starts months earlier in the Cerrado than in transitional sites, and
      even later in forest areas. Considerable synchrony was observed for reproductive
      phenology among populations and between biomes. Most phenological diversity was
      due to differences among individuals within populations. CONCLUSION: In spite of
      environmental differences, P. reticulata from the Atlantic Forest and Cerrado
      showed similar phenological behavior with only about 10% of the total diversity
      being attributed to differences between biomes.

PMID- 15972800
TI  - Haploinsufficiency of the cardiac transcription factor Nkx2-5 variably affects
      the expression of putative target genes.
AB  - Heterozygous mutations of the cardiac transcription factor Nkx2-5 cause
      congenital heart disease. To elucidate the molecular pathways of transcription
      factor mutant phenotypes or diseases, direct targets are commonly sought in
      studies of homozygous null mutant animals and by heterologous promoter-reporter
      gene transactivation assays. The expression of putative target genes in a
      physiologic range of transcription factor concentration, however, is often not
      examined. Heterozygous Nkx2-5 knockout (Nkx2-5+/-) mice have no more than half
      normal levels of Nkx2-5 protein. We therefore measured the mRNA expression of
      four putative targets of the cardiac transcription factor Nkx2-5 in wild-type and
      Nkx2-5+/- animals in a variety of developmental and pathologic states. Wild-type
      and Nkx2-5+/- embryonic hearts expressed similar levels of atrial natriuretic
      factor (ANF), brain natriuretic peptide (BNP), the RNA helicase Csm, and
      homeodomain only protein HOP. In the failing adult ventricle, ANF and BNP were up
      regulated to the same extent in wild-type and Nkx2-5+/- myocardium. Csm and HOP
      were down-regulated in heart failure, and Nkx2-5+/- hearts expressed about half
      normal levels in healthy and failing states. No consistent relationship existed
      between the expression of putative transcriptional targets and Nkx2-5 gene dosage
      in the physiologically relevant range. Any dependence of gene expression on Nkx2
      5 gene dosage is affected by factors specific to the individual gene and the
      physiologic context.

PMID- 15972801
TI  - Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage.
AB  - Niemann-Pick disease type C (NPC) is a genetic disorder in which patient cells
      exhibit lysosomal accumulation of cholesterol and sphingolipids (SLs) caused by
      defects in either NPC1 or NPC2 proteins. We previously demonstrated that NPC1
      human skin fibroblasts overexpressing endosomal Rab proteins (Rab7 or Rab9)
      showed a correction in the storage disease phenotype. In the current study, we
      used protein transduction to further investigate Rab9-mediated reduction of
      stored lipids in NPC cells. Recombinant human Rab9 fused with the herpes simplex
      virus VP22 protein fragment was overexpressed, purified, and added to culture
      medium to induce protein transduction. When VP22-Rab9 was transduced into NPC1
      fibroblasts, nearly all cells showed significant reduction in cellular free
      cholesterol levels, with no cytotoxicity up to 5 microM. A fraction of the VP22
      Rab9 that was transduced into the cells was shown to bind to rab GDP dissociation
      inhibitor, suggesting that this pool of VP22-Rab9 had become prenylated. The
      reduction in cellular free cholesterol was associated with correction of abnormal
      intracellular trafficking of BODIPY-lactosylceramide and an increase of sterols
      in the culture media. The clearance of lysosomal free cholesterol was also
      associated with a decrease in LDL-receptor levels. In addition, we demonstrated
      reduction of intracellular cholesterol by VP22-Rab9 transduction in NPC2
      fibroblasts and in cultured mouse NPC1 neurons. These observations provide
      important new information about the correction of membrane traffic in NPC cells
      by Rab9 overexpression and may lead to new therapeutic approaches for treatment
      of this disease.

PMID- 15972802
TI  - Early life immune challenge alters innate immune responses to lipopolysaccharide:
      implications for host defense as adults.
AB  - Fever is the most common manifestation of the innate immune response to invading
      pathogens. Animals prevented from developing fever have increased morbidity and
      mortality to infection. We now show that early life events can program this
      innate immune response, in that rats that have been challenged neonatally with
      the immune stimulant lipopolysaccharide (LPS) have both suppressed febrile
      responses to LPS as adults and significantly reduced nuclear factor (NF)-kappaB
      activation in peripheral immune organs. This was associated with reduced levels
      of proinflammatory cytokines tumor necrosis factor (TNF)-alpha, and interleukin-6
      (IL-6) in the plasma after adult LPS challenge, compared with animals that have
      received saline neonatally. In contrast, adult LPS challenge elicited higher
      corticosterone levels in the animals that had been treated neonatally with LPS.
      When this increased corticosterone response was negated by adrenalectomy or by
      administration of the glucocorticoid receptor antagonist RU-486, both the
      cytokine and febrile responses were normalized. This study indicates that the
      innate immune response can be programmed by a neonatal LPS challenge, whereby an
      amplified hypothalamic-pituitary-adrenal response causes reduced cytokine
      synthesis and an attenuated febrile response to an adult immune challenge. In
      light of the importance of fever in the host defense response, these alterations
      may have deleterious consequences on an individual's ability to combat disease
      later in life.

PMID- 15972803
TI  - An unusual internal ribosome entry site in the herpes simplex virus thymidine
      kinase gene.
AB  - We have investigated a herpes simplex virus mutant that expresses low levels of
      thymidine kinase (TK), a phenotype associated with drug resistance and
      pathogenicity, despite a single-base deletion in the gene. Using a dual-reporter
      system, a 39-nt sequence including the mutation was shown to direct expression of
      the downstream reporter gene in reticulocyte lysate. Translation of the
      downstream reporter was not impaired when the mRNA lacked a 5' cap or had a
      stable stem loop 5' of the upstream reporter and was relatively resistant to
      edeine, an antibiotic that prevents AUG codon recognition by the 40S-eIF2-GTP/Met
      tRNAi complex. Twelve nucleotides were as active as the original sequence for
      translation of the downstream reporter. Surprisingly, this sequence lacks an AUG
      codon. Analysis of point mutations showed that a CUG codon in the sequence was
      important. However, many single-base changes had only limited effects, and
      introduction of AUG codons did not increase translation. A mutant virus
      containing both the single-base deletion and a mutation that reduced downstream
      translation in vitro had significantly less TK activity than a virus with the
      single-base deletion alone. Thus, a remarkably short internal ribosome entry site
      (IRES) that lacks an AUG codon resides in the viral tk gene. The IRES appears to
      be responsible for TK expression from a drug-resistant mutant that would
      otherwise express no TK, which may contribute to pathogenicity. Because we found
      numerous short sequences with IRES activity, there might be many hitherto
      unrecognized polypeptides expressed at low levels from eukaryotic mRNAs.

PMID- 15972804
TI  - Hydrophobic hydration from small to large lengthscales: Understanding and
      manipulating the crossover.
AB  - Small and large hydrophobic solutes exhibit remarkably different hydration
      thermodynamics. Small solutes are accommodated in water with minor perturbations
      to water structure, and their hydration is captured accurately by theories that
      describe density fluctuations in pure water. In contrast, hydration of large
      solutes is accompanied by dewetting of their surfaces and requires a macroscopic
      thermodynamic description. A unified theoretical description of these lengthscale
      dependencies was presented by Lum, Chandler, and Weeks [(1999) J. Phys. Chem. B
      103, 4570-4577]. Here, we use molecular simulations to study lengthscale
      dependent hydrophobic hydration under various thermodynamic conditions. We show
      that the hydration of small and large solutes displays disparate dependencies on
      thermodynamic variables, including pressure, temperature, and additive
      concentration. Understanding these dependencies allows manipulation of the small
      to-large crossover lengthscale, which is nanoscopic under ambient conditions.
      Specifically, applying hydrostatic tension or adding ethanol decreases the
      crossover length to molecular sizes, making it accessible to atomistic
      simulations. With detailed temperature-dependent studies, we further demonstrate
      that hydration thermodynamics changes gradually from entropic to enthalpic near
      the crossover. The nanoscopic lengthscale of the crossover and its sensitivity to
      thermodynamic variables imply that quantitative modeling of biomolecular self
      assembly in aqueous solutions requires elements of both molecular and macroscopic
      hydration physics. We also show that the small-to-large crossover is directly
      related to the Egelstaff-Widom lengthscale, the product of surface tension and
      isothermal compressibility, which is another fundamental lengthscale in liquids.

PMID- 15972805
TI  - Eutrophication of aquatic ecosystems: bistability and soil phosphorus.
AB  - Eutrophication (the overenrichment of aquatic ecosystems with nutrients leading
      to algal blooms and anoxic events) is a persistent condition of surface waters
      and a widespread environmental problem. Some lakes have recovered after sources
      of nutrients were reduced. In others, recycling of phosphorus from sediments
      enriched by years of high nutrient inputs causes lakes to remain eutrophic even
      after external inputs of phosphorus are decreased. Slow flux of phosphorus from
      overfertilized soils may be even more important for maintaining eutrophication of
      lakes in agricultural regions. This type of eutrophication is not reversible
      unless there are substantial changes in soil management. Technologies for rapidly
      reducing phosphorus content of overenriched soils, or reducing erosion rates, are
      needed to improve water quality.

PMID- 15972806
TI  - Regulating the proton budget of higher plant photosynthesis.
AB  - In higher plant chloroplasts, transthylakoid proton motive force serves both to
      drive the synthesis of ATP and to regulate light capture by the photosynthetic
      antenna to prevent photodamage. In vivo probes of the proton circuit in wild-type
      and a mutant strain of Arabidopsis thaliana show that regulation of light capture
      is modulated primarily by altering the resistance of proton efflux from the
      thylakoid lumen, whereas modulation of proton influx through cyclic electron flow
      around photosystem I is suggested to play a role in regulating the ATP/NADPH
      output ratio of the light reactions.

PMID- 15972807
TI  - Mechanics of receptor-mediated endocytosis.
AB  - Most viruses and bioparticles endocytosed by cells have characteristic sizes in
      the range of tens to hundreds of nanometers. The process of viruses entering and
      leaving animal cells is mediated by the binding interaction between ligand
      molecules on the viral capid and their receptor molecules on the cell membrane.
      How does the size of a bioparticle affect receptor-mediated endocytosis? Here, we
      study how a cell membrane containing diffusive mobile receptors wraps around a
      ligand-coated cylindrical or spherical particle. It is shown that particles in
      the size range of tens to hundreds of nanometers can enter or exit cells via
      wrapping even in the absence of clathrin or caveolin coats, and an optimal
      particles size exists for the smallest wrapping time. This model can also be
      extended to include the effect of clathrin coat. The results seem to show broad
      agreement with experimental observations.

PMID- 15972808
TI  - Neighborliness of randomly projected simplices in high dimensions.
AB  - Let A be a d x n matrix and T = T(n-1) be the standard simplex in Rn. Suppose
      that d and n are both large and comparable: d approximately deltan, delta in (0,
      1). We count the faces of the projected simplex AT when the projector A is chosen
      uniformly at random from the Grassmann manifold of d-dimensional orthoprojectors
      of Rn. We derive rhoN(delta) > 0 with the property that, for any rho <
      rhoN(delta), with overwhelming probability for large d, the number of k
      dimensional faces of P = AT is exactly the same as for T, for 0 < or = k < or =
      rhod. This implies that P is left floor rhod right floor-neighborly, and its
      skeleton Skel(left floor rhod right floor)(P) is combinatorially equivalent to
      Skel( left floor rhod right floor)(T). We also study a weaker notion of
      neighborliness where the numbers of k-dimensional faces f(k)(P) > or = f(k)(T)(1
      epsilon). Vershik and Sporyshev previously showed existence of a threshold
      rhoVS(delta) > 0 at which phase transition occurs in k/d. We compute and display
      rhoVS and compare with rhoN. Corollaries are as follows. (1) The convex hull of n
      Gaussian samples in Rd, with n large and proportional to d, has the same k
      skeleton as the (n-1) simplex, for k < rhoN (d/n)d(1 + oP(1)). (2) There is a
      "phase transition" in the ability of linear programming to find the sparsest
      nonnegative solution to systems of underdetermined linear equations. For most
      systems having a solution with fewer than rhoVS(d/n)d(1 + o(1)) nonzeros, linear
      programming will find that solution.

PMID- 15972809
TI  - An intracellular phosphate buffer filters transient fluctuations in extracellular
      phosphate levels.
AB  - To survive in a dynamic and unpredictable environment, cells must correctly
      interpret and integrate extracellular signals with internal factors. In
      particular, internal stores of nutrients must be managed for use during periods
      of nutrient limitation. To gain insight into this complex process, we combined
      biochemical and spectroscopic techniques to follow the dynamics of the phosphate
      responsive signaling pathway in both single yeast cells and populations. We
      demonstrate that the phosphate-responsive genes PHO5 and PHO84 exhibit different
      kinetics of transcriptional induction in response to phosphate starvation, and
      that transient phosphate limitation causes induction of PHO84 but not PHO5. This
      differential kinetic behavior is largely eliminated in cells that lack the
      ability to store phosphate internally in the form of polyphosphate, but the
      threshold of external phosphate required for induction of PHO5 and PHO84 is
      unaffected. Our observations indicate that polyphosphate acts as a buffer that
      can be mobilized during periods of phosphate limitation and enables the phosphate
      responsive signaling pathway to filter transient fluctuations in extracellular
      phosphate levels.

PMID- 15972810
TI  - Reversible single-molecule photoswitching in the GFP-like fluorescent protein
      Dronpa.
AB  - Reversible photoswitching of individual molecules has been demonstrated for a
      number of mutants of the green fluorescent protein (GFP). To date, however, a
      limited number of switching events with slow response to light have been achieved
      at the single-molecule level. Here, we report reversible photoswitching
      characteristics observed in individual molecules of Dronpa, a mutant of a GFP
      like fluorescent protein that was cloned from a coral Pectiniidae. Ensemble
      spectroscopy shows that intense irradiation at 488 nm changes Dronpa to a dim
      protonated form, but even weak irradiation at 405 nm restores it to the bright
      deprotonated form. Although Dronpa exists in an acid-base equilibrium, only the
      photoinduced protonated form shows the switching behavior. At the single-molecule
      level, 488- and 405-nm lights can be used to drive the molecule back and forth
      between the bright and dim states. Such reversible photoswitching could be
      repeated >100 times. The response speed to irradiation depends almost linearly on
      the irradiation power, with the response time being in the order of milliseconds.
      The perfect reversibility of the Dronpa photoswitching allows us to propose a
      detailed model, which quantitatively describes interconversion among the various
      states. The fast response of Dronpa to light holds great promise for following
      fast diffusion or transport of signaling molecules in live cells.

PMID- 15972811
TI  - Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal
      muscle function in heart failure.
AB  - Abnormalities in intracellular calcium release and reuptake are responsible for
      decreased contractility in heart failure (HF). We have previously shown that
      cardiac ryanodine receptors (RyRs) are protein kinase A-hyperphosphorylated and
      depleted of the regulatory subunit calstabin-2 in HF. Moreover, similar
      alterations in skeletal muscle RyR have been linked to increased fatigability in
      HF. To determine whether restoration of calstabin binding to RyR may ameliorate
      cardiac and skeletal muscle dysfunction in HF, we treated WT and calstabin-2-/-
      mice subjected to myocardial infarction (MI) with JTV519. JTV519, a 1,4
      benzothiazepine, is a member of a class of drugs known as calcium channel
      stabilizers, previously shown to increase calstabin binding to RyR.
      Echocardiography at 21 days after MI demonstrated a significant increase in
      ejection fraction in WT mice treated with JTV519 (45.8 +/- 5.1%) compared with
      placebo (31.1 +/- 3.1%; P < 0.05). Coimmunoprecipitation experiments revealed
      increased amounts of calstabin-2 bound to the RyR2 channel in JTV519-treated WT
      mice. However, JTV519 did not show any of these beneficial effects in calstabin-2
      /- mice with MI. Additionally, JTV519 improved skeletal muscle fatigue in WT and
      calstabin-2-/- mice with HF by increasing the binding of calstabin-1 to RyR1. The
      observation that treatment with JTV519 improved cardiac function in WT but not
      calstabin-2-/- mice indicates that calstabin-2 binding to RyR2 is required for
      the beneficial effects in failing hearts. We conclude that JTV519 may provide a
      specific way to treat the cardiac and skeletal muscle myopathy in HF by
      increasing calstabin binding to RyR.

PMID- 15972812
TI  - Hysteresis in a synthetic mammalian gene network.
AB  - Bistable and hysteretic switches, enabling cells to adopt multiple internal
      expression states in response to a single external input signal, have a pivotal
      impact on biological systems, ranging from cell-fate decisions to cell-cycle
      control. We have designed a synthetic hysteretic mammalian transcription network.
      A positive feedback loop, consisting of a transgene and transactivator (TA)
      cotranscribed by TA's cognate promoter, is repressed by constitutive expression
      of a macrolide-dependent transcriptional silencer, whose activity is modulated by
      the macrolide antibiotic erythromycin. The antibiotic concentration, at which a
      quasi-discontinuous switch of transgene expression occurs, depends on the history
      of the synthetic transcription circuitry. If the network components are
      imbalanced, a graded rather than a quasi-discontinuous signal integration takes
      place. These findings are consistent with a mathematical model. Synthetic gene
      networks, which are able to emulate natural gene expression behavior, may foster
      progress in future gene therapy and tissue engineering initiatives.

PMID- 15972813
TI  - Nonlinear protein degradation and the function of genetic circuits.
AB  - The functions of most genetic circuits require a sufficient degree of
      cooperativity in the circuit components. Although mechanisms of cooperativity
      have been studied most extensively in the context of transcriptional initiation
      control, cooperativity from other processes involved in the operation of the
      circuits can also play important roles. In this work, we examine a simple kinetic
      source of cooperativity stemming from the nonlinear degradation of multimeric
      proteins. Ample experimental evidence suggests that protein subunits can degrade
      less rapidly when associated in multimeric complexes, an effect we refer to as
      "cooperative stability." For dimeric transcription factors, this effect leads to
      a concentration-dependence in the degradation rate because monomers, which are
      predominant at low concentrations, will be more rapidly degraded. Thus,
      cooperative stability can effectively widen the accessible range of protein
      levels in vivo. Through theoretical analysis of two exemplary genetic circuits in
      bacteria, we show that such an increased range is important for the robust
      operation of genetic circuits as well as their evolvability. Our calculations
      demonstrate that a few-fold difference between the degradation rate of monomers
      and dimers can already enhance the function of these circuits substantially. We
      discuss molecular mechanisms of cooperative stability and their occurrence in
      natural or engineered systems. Our results suggest that cooperative stability
      needs to be considered explicitly and characterized quantitatively in any
      systematic experimental or theoretical study of gene circuits.

PMID- 15972814
TI  - Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated
      channels in HEK-293 cells.
AB  - Endogenously expressed canonical transient receptor potential (TRPC) homologs
      were investigated for their role in forming store-operated, 1-oleoyl-2-acetyl-sn
      glycerol-stimulated, or carbachol (CCh)-stimulated calcium entry pathways in HEK
      293 cells. Measurement of thapsigargin-stimulated Ba(2+) entry indicated that the
      individual suppression of TRPC1, TRPC3, or TRPC7 protein levels, by small
      interfering RNA (siRNA) techniques, dramatically inhibited (52-68%) store
      operated calcium entry (SOCE), whereas suppression of TRPC4 or TRPC6 had no
      effect. Combined suppression of TRPC1-TRPC3, TRPC1-TRPC7, TRPC3-TRPC7, or TRPC1
      TRPC3-TRPC7 gave only slightly more inhibition of SOCE (74-78%) than seen with
      suppression of TRPC1 alone (68%), suggesting that these three TRPC homologs work
      in tandem to mediate a large component of SOCE. Evidence from co
      immunoprecipitation experiments indicates that a TRPC1-TRPC3-TRPC7 complex,
      predicted from siRNA results, does exist. The suppression of either TRPC3 or
      TRPC7, but not TRPC1, induced a high Ba(2+) leak flux that was inhibited by 2-APB
      and SKF96365, suggesting that the influx is via leaky store-operated channels.
      The high Ba(2+) leak flux is eliminated by co-suppression of TRPC1-TRPC3 or TRPC1
      TRPC7. For 1-oleoyl-2-acetyl-sn-glycerol-stimulated cells, siRNA data indicate
      that TRPC1 plays no role in mediating Ba(2+) entry, which appears to be mediated
      by the participation of TRPC3, TRPC4, TRPC6, and TRPC7. CCh-stimulated Ba(2+)
      entry, on the other hand, could be inhibited by suppression of any of the five
      endogenously expressed TRPC homologs, with the degree of inhibition being
      consistent with CCh stimulation of both store-operated and receptor-operated
      channels. In summary, endogenous TRPC1, TRPC3, and TRPC7 participate in forming
      heteromeric store-operated channels, whereas TRPC3 and TRPC7 can also participate
      in forming heteromeric receptor-operated channels.

PMID- 15972815
TI  - Thermostable mutants of the photoprotein aequorin obtained by in vitro evolution.
AB  - Aequorin is a photoprotein that emits light upon binding calcium. Aequorin
      mutants showing increased intensity or slow decay of bioluminescence were
      isolated by in vitro evolution combining DNA shuffling and functional screening
      in bacteria. Luminescence decay mutants were isolated at the first round of
      screening and carried mutations located in EF-hand calcium binding sites or their
      vicinity. During in vitro evolution, the luminescence intensity of the population
      of mutants increased with the frequency of effective mutations whereas the
      frequency of other amino acid substitutions remained roughly stable. Luminescence
      intensity mutations neighbored the His-16 or His-169 coelenterazine binding
      residues or were located in the first EF-hand. None of the selected mutants
      exhibited an increase in photon yield when examined in a cell-free assay.
      However, we observed that two mutants, Q168R and L170I, exhibited an increase of
      the photoprotein lifetime at 37 degrees C that may underlie their high
      luminescence intensity in bacteria. Further analysis of Q168R and L170I mutations
      showed that they increased aequorin thermostability. Conversely, examination of
      luminescence decay mutants revealed that the F149S substitution decreased
      aequorin thermostability. Finally, screening of a library of random Gln-168 and
      Leu-170 mutants confirmed the involvement of both positions in thermostability
      and indicated that optimal thermostability was conferred by Q168R and L170I
      mutations selected through in vitro evolution. Our results suggest that Phe-149
      and Gln-168 residues participate in stabilization of the coelenterazine peroxide
      and the triggering of photon emission by linking the third EF-hand to Trp-129 and
      His-169 coelenterazine binding residues.

PMID- 15972816
TI  - Identification of the amino acid residue of CYP27B1 responsible for binding of 25
      hydroxyvitamin D3 whose mutation causes vitamin D-dependent rickets type 1.
AB  - We previously reported the three-dimensional structure of human CYP27B1 (25
      hydroxyvitamin D3 1alpha-hydroxylase) constructed by homology modeling. Using the
      three-dimensional model we studied the docking of the substrate, 25
      hydroxyvitamin D3, into the substrate binding pocket of CYP27B1. In this study,
      we focused on the amino acid residues whose point mutations cause vitamin D
      dependent rickets type 1, especially unconserved residues among mitochondrial
      CYPs such as Gln65 and Thr409. Recently, we successfully overexpressed mouse
      CYP27B1 by using a GroEL/ES co-expression system. In a mutation study of mouse
      CYP27B1 that included spectroscopic analysis, we concluded that in a 1alpha
      hydroxylation process, Ser408 of mouse CYP27B1 corresponding to Thr409 of human
      CYP27B1 forms a hydrogen bond with the 25-hydroxyl group of 25-hydroxyvitamin D3.
      This is the first report that shows a critical amino acid residue recognizing the
      25-hydroxyl group of the vitamin D3.

PMID- 15972817
TI  - Cardiolipin is essential for organization of complexes III and IV into a
      supercomplex in intact yeast mitochondria.
AB  - Digitonin extracts of mitochondria from cardiolipin-containing (wild type) and
      cardiolipin-lacking (crd1Delta mutant) Saccharomyces cerevisiae subjected to
      colorless native polyacrylamide gel electrophoresis in the presence of 0.003%
      digitonin displayed a supercomplex composed of homodimers of complexes III and IV
      in the former case but only the individual homodimers in the latter case. To
      avoid treatment with any detergent or dye, we compared organization of the
      respiratory chain in intact mitochondria from wild type and cardiolipin-lacking
      cells by using a functional analysis developed previously for the study of the
      organization of the respiratory chain of S. cerevisiae (Boumans, H., Grivell, L.
      A., and Berden, J. A. (1998) J. Biol. Chem. 273, 4872-4877). Dependence of the
      kinetics of NADH oxidation via complexes III, IV, and cytochrome c on the
      concentration of the complex III-specific inhibitor antimycin A was studied. A
      linear relationship between respiratory activity and saturation of complex III
      with antimycin A was obtained for wild type mitochondria consistent with single
      functional unit kinetics of the respiratory chain. Under the same conditions,
      cardiolipin-lacking mitochondria displayed a hyperbolic relationship indicating
      cytochrome c pool behavior. No release of cytochrome c from cardiolipin-lacking
      mitochondria or mitoplasts under our standard experimental conditions was
      detected. Identical cytochrome c pool behavior was observed for both wild type
      and cardiolipin-lacking mitochondria in the presence of a chaotropic agent, which
      disrupts the interaction between respiratory complexes. The results demonstrate
      that cardiolipin is essential for association of complexes III and IV into a
      supercomplex in intact yeast mitochondria.

PMID- 15972818
TI  - Identification and characterization of human archaemetzincin-1 and -2, two novel
      members of a family of metalloproteases widely distributed in Archaea.
AB  - Systematic analysis of degradomes, the complete protease repertoires of
      organisms, has demonstrated the large and growing complexity of proteolytic
      systems operating in all cells and tissues. We report here the identification of
      two new human metalloproteases that have been called archaemetzincin-1 (AMZ1) and
      archaemetzincin-2 (AMZ2) to emphasize their close relationship to putative
      proteases predicted by bioinformatic analysis of archaeal genomes. Both human
      proteins contain a catalytic domain with a core motif (HEXXHXXGX3CX4CXMX17CXXC)
      that includes an archetypal zinc-binding site, the methionine residue
      characteristic of metzincins, and four conserved cysteine residues that are not
      present at the equivalent positions of other human metalloproteases. Analysis of
      genome sequence databases revealed that AMZs are widely distributed in Archaea
      and vertebrates and contribute to the defining of a new metalloprotease family
      that has been called archaemetzincin. However, AMZ-like sequences are absent in a
      number of model organisms from bacteria to nematodes. Phylogenetic analysis
      showed that these enzymes have undergone a complex evolutionary process involving
      a series of lateral gene transfer, gene loss, and genetic duplication events that
      have shaped this novel family of metalloproteases. Northern blot analysis showed
      that AMZ1 and AMZ2 exhibit distinct expression patterns in human tissues. AMZ1 is
      mainly detected in liver and heart whereas AMZ2 is predominantly expressed in
      testis and heart, although both are also detectable at lower levels in other
      tissues. Both human enzymes were produced in Escherichia coli, and the purified
      recombinant proteins hydrolyzed synthetic substrates and bioactive peptides,
      demonstrating that they are functional proteases. Finally, these activities were
      abolished by inhibitors of metalloproteases, providing further evidence that AMZs
      belong to this catalytic class of proteolytic enzymes.

PMID- 15972819
TI  - Structure and properties of the C-terminal domain of insulin-like growth factor
      binding protein-1 isolated from human amniotic fluid.
AB  - Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) regulates the
      activity of the insulin-like growth factors in early pregnancy and is, thus,
      thought to play a key role at the fetal-maternal interface. The C-terminal domain
      of IGFBP-1 and three isoforms of the intact protein were isolated from human
      amniotic fluid, and sequencing of the four N-terminal polypeptide chains showed
      them to be highly pure. The addition of both intact IGFBP-1 and its C-terminal
      fragment to cultured fibroblasts has a similar stimulating effect on cell
      migration, and therefore, the domain has a biological activity on its own. The
      three-dimensional structure of the C-terminal domain was determined by x-ray
      crystallography to 1.8 Angstroms resolution. The fragment folds as a
      thyroglobulin type I domain and was found to bind the Fe(2+) ion in the crystals
      through the only histidine residue present in the polypeptide chain. Iron (II)
      decreases the binding of intact IGFBP-1 and the C-terminal domain to IGF-II,
      suggesting that the metal binding site is close to or part of the surface of
      interaction of the two molecules.

PMID- 15972820
TI  - Keratin 8 phosphorylation by protein kinase C delta regulates shear stress
      mediated disassembly of keratin intermediate filaments in alveolar epithelial
      cells.
AB  - Phosphorylation of keratin intermediate filaments (IF) is known to affect their
      assembly state and organization; however, little is known about the mechanisms
      regulating keratin phosphorylation. In this study, we demonstrate that shear
      stress, but not stretch, causes disassembly of keratin IF in lung alveolar
      epithelial cells (AEC) and that this disassembly is regulated by protein kinase C
      delta-mediated phosphorylation of keratin 8 (K8) Ser-73. Specifically, in AEC
      subjected to shear stress, keratin IF are disassembled, as reflected by their
      increased solubility. In contrast, AEC subjected to stretch showed no changes in
      the state of assembly of IF. Pretreatment with the protein kinase C (PKC)
      inhibitor, bisindolymaleimide, prevents the increase in solubility of either K8
      or its assembly partner K18 in shear-stressed AEC. Phosphoserine-specific
      antibodies demonstrate that K8 Ser-73 is phosphorylated in a time-dependent
      manner in shear-stressed AEC. Furthermore, we showed that shear stress activates
      PKC delta and that the PKC delta peptide antagonist, delta V1-1, significantly
      attenuates the shear stress-induced increase in keratin phosphorylation and
      solubility. These data suggested that shear stress mediates the phosphorylation
      of serine residues in K8, leading to the disassembly of IF in alveolar epithelial
      cells. Importantly, these data provided clues regarding a molecular link between
      mechanically induced signal transduction and alterations in cytoskeletal IF.

PMID- 15972821
TI  - Interactions of the N-terminal domain of ribosomal protein L11 with thiostrepton
      and rRNA.
AB  - Ribosomal protein L11 has two domains: the C-terminal domain (L11-C76) binds
      rRNA, whereas the N-terminal domain (L11-NTD) may variously interact with
      elongation factor G, the antibiotic thiostrepton, and rRNA. To begin to
      quantitate these interactions, L11 from Bacillus stearothermophilus has been
      overexpressed and its properties compared with those of L11-C76 alone in a
      fluorescence assay for protein-rRNA binding. The assay relies on 2'-amino-butyryl
      pyrene-uridine incorporated in a 58-nucleotide rRNA fragment, which gives
      approximately 15-fold enhancement when L11 or L11-C76 is bound. Although the
      pyrene tag weakens protein binding, unbiased protein-RNA association constants
      were obtained in competition experiments with untagged RNA. It was found that (i)
      intact B. stearothermophilus L11 binds rRNA with K approximately 1.2 x 10(9) m(
      1) in buffers with 0.2 m KCl, about 100-fold tighter than Escherichia coli L11;
      (ii) the N-terminal domain makes a small, salt-dependent contribution to the
      overall L11-RNA binding affinity (approximately 8-fold enhancement at 0.2 m KCl),
      (iii) L11 stimulates thiostrepton binding by 2.3 +/- 0.6 x 10(3)-fold, predicting
      an overall thiostrepton affinity for the ribosome of approximately 10(9) m(-1),
      and (iv) the yeast homolog of L11 shows no stimulation of thiostrepton binding.
      The latter observation resolves the question of why eukaryotes are insensitive to
      the antibiotic. These measurements also show that it is plausible for
      thiostrepton to compete directly with EF-G.GDP for binding to the L11-RNA
      complex, and provide a quantitative basis for further studies of L11 function and
      thiostrepton mechanism.

PMID- 15972822
TI  - A role for glycogen synthase kinase-3beta in the mammalian circadian clock.
AB  - The Drosophila shaggy gene product is a mammalian glycogen synthase kinase-3beta
      (GSK-3beta) homologue that contributes to the circadian clock of the Drosophila
      through TIMELESS phosphorylation, and it regulates nuclear translocation of the
      PERIOD/TIMELESS heterodimer. We found that mammalian GSK-3beta is expressed in
      the suprachiasmatic nucleus and liver of mice and that GSK-3beta phosphorylation
      exhibits robust circadian oscillation. Rhythmic GSK-3beta phosphorylation is also
      observed in serum-shocked NIH3T3 cells. Exposing serum-shocked NIH3T3 cells to
      lithium chloride, a specific inhibitor of GSK-3beta, increases GSK-3beta
      phosphorylation and delays the phase of rhythmic clock gene expression. On the
      other hand, GSK-3beta overexpression advances the phase of clock gene expression.
      We also found that GSK-3beta interacts with PERIOD2 (PER2) in vitro and in vivo.
      Recombinant GSK-3beta can phosphorylate PER2 in vitro. GSK-3beta promotes the
      nuclear translocation of PER2 in COS1 cells. The present data suggest that GSK
      3beta plays important roles in mammalian circadian clock.

PMID- 15972823
TI  - Characterization of the G alpha(s) regulator cysteine string protein.
AB  - Cysteine string protein (CSP) is an abundant regulated secretory vesicle protein
      that is composed of a string of cysteine residues, a linker domain, and an N
      terminal J domain characteristic of the DnaJ/Hsp40 co-chaperone family. We have
      shown previously that CSP associates with heterotrimeric GTP-binding proteins (G
      proteins) and promotes G protein inhibition of N-type Ca2+ channels. To elucidate
      the mechanisms by which CSP modulates G protein signaling, we examined the
      effects of CSP(1-198) (full-length), CSP(1-112), and CSP(1-82) on the kinetics of
      guanine nucleotide exchange and GTP hydrolysis. In this report, we demonstrate
      that CSP selectively interacts with G alpha(s) and increases steady-state GTP
      hydrolysis. CSP(1-198) modulation of G alpha(s) was dependent on Hsc70 (70-kDa
      heat shock cognate protein) and SGT (small glutamine-rich tetratricopeptide
      repeat domain protein), whereas modulation by CSP(1-112) was Hsc70-SGT
      independent. CSP(1-112) preferentially associated with the inactive GDP-bound
      conformation of G alpha(s). Consistent with the stimulation of GTP hydrolysis,
      CSP(1-112) increased guanine nucleotide exchange of G alpha(s). The interaction
      of native G alpha(s) and CSP was confirmed by coimmunoprecipitation and showed
      that G alpha(s) associates with CSP. Furthermore, transient expression of CSP in
      HEK cells increased cellular cAMP levels in the presence of the beta2 adrenergic
      agonist isoproterenol. Together, these results demonstrate that CSP modulates G
      protein function by preferentially targeting the inactive GDP-bound form of G
      alpha(s) and promoting GDP/GTP exchange. Our results show that the guanine
      nucleotide exchange activity of full-length CSP is, in turn, regulated by Hsc70
      SGT.

PMID- 15972824
TI  - Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity.
AB  - Duox2 (and probably Duox1) is a glycoflavoprotein involved in thyroid hormone
      biosynthesis, as the thyroid H2O2 generator functionally associated with Tpo
      (thyroperoxidase). So far, because of the impairment of maturation and of the
      targeting process, transfecting DUOX into nonthyroid cell lines has not led to
      the expression of a functional H2O2-generating system at the plasma membrane. For
      the first time, we investigated the H2O2-generating activity in the particulate
      fractions from DUOX2- and DUOX1-transfected HEK293 and Chinese hamster ovary
      cells. The particulate fractions of these cells stably or transiently transfected
      with human or porcine DUOX cDNA demonstrate a functional NADPH/Ca2+-dependent
      H2O2-generating activity. The immature Duox proteins had less activity than pig
      thyrocyte particulate fractions, and their activity depended on their primary
      structures. Human Duox2 seemed to be more active than human Duox1 but only half
      as active as its porcine counterpart. TPO co-transfection produced a slight
      increase in the enzymatic activity, whereas p22(phox), the 22-kDa subunit of the
      leukocyte NADPH oxidase, had no effect. In previous studies on the mechanism of
      H2O2 formation, it was shown that mature thyroid NADPH oxidase does not release
      O2*- but H2O2. Using a spin-trapping technique combined with electron
      paramagnetic resonance spectroscopy, we confirmed this result but also
      demonstrated that the partially glycosylated form of Duox2, located in the
      endoplasmic reticulum, generates superoxide in a calcium-dependent manner. These
      results suggest that post-translational modifications during the maturation
      process of Duox2 could be implicated in the mechanism of H2O2 formation by
      favoring intramolecular superoxide dismutation.

PMID- 15972825
TI  - Nonfixed relationship of the Michaelis constant and maximum velocity with their
      corresponding rate constants.
AB  - The Michaelis constant (K(m)) and V(mas) (E0k(cat)) values for two mutant sets of
      enzymes were studied from the viewpoint of their definition in a rapid
      equilibrium reaction model and in a steady state reaction model. The "AMP set
      enzyme" had a mutation at the AMP-binding site (Y95F, V67I, and V67I/L76V), and
      the "ATP set enzyme" had a mutation at a possible ATP-binding region (Y32F, Y34F,
      and Y32A/Y34A). Reaction rate constants obtained using steady state model
      analysis explained discrepancies found by the rapid equilibrium model analysis.
      (i) The unchanged number of bound AMPs for Y95F and the wild type despite the
      markedly increased K(m) values for AMP of the AMP set of enzymes was explained by
      alteration of the rate constants of the AMP step (k(+2), k(-2)) to retain the
      ratio k(+2)/k(-2). (ii) A 100 times weakened selectivity of ATP for Y34F in
      contrast to no marked changes in K(m) values for both ATP and AMP for the ATP set
      of enzymes was explained by the alteration of the rate constants of the ATP
      steps. A similar alteration of the K(m) and k(cat) values of these enzymes
      resulted from distinctive alterations of their rate constants. The pattern of
      alteration was highly suggestive. The most interesting finding was that the rate
      constants that decided the K(m) and k(cat) values were replaced by the mutation,
      and the simple relationships between K(m), k(cat), and the rate constants of
      K(m)1 = k(+1)/k(-1) and k(cat) = k(f) were not valid. The nature of the K(m) and
      k(cat) alterations was discussed.

PMID- 15972826
TI  - Structure-function analysis of the three domains of RuvB DNA motor protein.
AB  - RuvB protein forms two hexameric rings that bind to the RuvA tetramer at DNA
      Holliday junctions. The RuvAB complex utilizes the energy of ATP hydrolysis to
      promote branch migration of Holliday junctions. The crystal structure of RuvB
      from Thermus thermophilus (Tth) HB8 showed that each RuvB monomer has three
      domains (N, M, and C). This study is a structure-function analysis of the three
      domains of RuvB. The results show that domain N is involved in RuvA-RuvB and RuvB
      RuvB subunit interactions, domains N and M are required for ATP hydrolysis and
      ATP binding-induced hexamer formation, and domain C plays an essential role in
      DNA binding. The side chain of Arg-318 is essential for DNA binding and may
      directly interact with DNA. The data also provide evidence that coordinated ATP
      dependent interactions between domains N, M, and C play an essential role during
      formation of the RuvAB Holliday junction ternary complex.

PMID- 15972827
TI  - Intermolecular contact between globular N-terminal fold and C-terminal domain of
      ApoA-I stabilizes its lipid-bound conformation: studies employing chemical cross
      linking and mass spectrometry.
AB  - The structure of apoA-I on discoidal high density lipoprotein (HDL) was studied
      using a combination of chemical cross-linking and mass spectrometry. Recombinant
      HDL particles containing 145 molecules of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine and two molecules of apoA-I with a 96-A diameter were treated with
      the lysine-specific cross-linker, dithiobis(succinimidylpropionate) at varying
      molar ratios from 2:1 to 200:1. At low molar ratios of
      dithiobis(succinimidylpropionate) to apoA-I, two products were obtained
      corresponding to approximately 53 and approximately 80 kDa. At high molar ratios,
      these two products merged, yielding a product of approximately 59 kDa, close to
      the theoretical molecular mass of dimeric apoA-I. To identify the intermolecular
      cross-links giving rise to the two different sized products, bands were excised
      from the gel, digested with trypsin, and then analyzed by liquid chromatography
      electrospray-tandem mass spectrometry. In addition, tandem mass spectrometry of
      unique cross-links found in the 53- and 80-kDa products suggested that a distinct
      conformation exists for lipid-bound apoA-I on 96-A recombinant HDL, emphasizing
      the inherent flexibility and malleability of the N termini and its interaction
      with its C-terminal domain.

PMID- 15972828
TI  - Presynaptic modulation of synaptic transmission by pregnenolone sulfate as
      studied by optical recordings.
AB  - The effects of pregnenolone sulfate (PREGS), a putative neurosteroid, on the
      transmission of perforant path-granule cell synapses were investigated with an
      optical recording technique in rat hippocampal slices stained with voltage
      sensitive dyes. Application of PREGS to the bath solution resulted in an acute
      augmentation of EPSP in a dose-dependent manner. The PREGS effect was dependent
      on the extracellular Ca(2+) concentration ([Ca(2+)](o)), but independent of NMDA
      receptor activation. PREGS caused a decrease in paired-pulse facilitation, which
      implies that PREGS positively modulates presynaptic neurotransmitter releases.
      Firmer support for this mechanism was that PREGS augmented the synaptically
      induced glial depolarization (SIGD) that reflects the activity of electrogenic
      glutamate transporters in glial cells during the uptake of released glutamate.
      The selective alpha7nAChR antagonist alpha-BGT or MLA prevented the SIGD increase
      by PREGS. Furthermore DMXB, a selective alpha7nAChR agonist, mimicked the PREGS
      effect on SIGD and antagonized the effect of PREGS. The presynaptic effect of
      PREGS was partially attenuated by the L-type Ca(2+) channel (VGCC) blocker
      nifedipine. Based on these findings, we proposed a novel mechanism underlying the
      facilitated synaptic transmission by PREGS: this neurosteroid sensitizes
      presynaptic alpha7nAChR that is followed by an activation of L-type VGCC to
      increase the presynaptic glutamate release.

PMID- 15972829
TI  - Neuromuscular adaptation during skill acquisition on a two degree-of-freedom
      target-acquisition task: dynamic movement.
AB  - In this experiment, we examined the extent to which the spatiotemporal
      reorganization of muscle synergies mediates skill acquisition on a two degree-of
      freedom (df) target-acquisition task. Eight participants completed five practice
      sessions on consecutive days. During each session they practiced movements to
      eight target positions presented by a visual display. The movements required
      combinations of flexion/extension and pronation/supination of the elbow joint
      complex. During practice sessions, eight targets displaced 5.4 cm from the start
      position (representing joint excursions of 54 degrees) were presented 16 times.
      During pre- and posttests, participants acquired the targets at two distances
      (3.6 cm [36 degrees] and 7.2 cm [72 degrees]). EMG data were recorded from eight
      muscles contributing to the movements during the pre- and posttests. Most targets
      were acquired more rapidly after the practice period. Performance improvements
      were, in most target directions, accompanied by increases in the smoothness of
      the movement trajectories. When target acquisition required movement in both dfs,
      there were also practice-related decreases in the extent to which the
      trajectories deviated from a direct path to the target. The contribution of
      monofunctional muscles (those producing torque in a single df) increased with
      practice during movements in which they acted as agonists. The activity in
      bifunctional muscles (those contributing torque in both dfs) remained at pretest
      levels in most movements. The results suggest that performance gains were
      mediated primarily by changes in the spatial organization of muscles synergies.
      These changes were expressed most prominently in terms of the magnitude of
      activation of the monofunctional muscles.

PMID- 15972831
TI  - Functional heterogeneity among neurons in the nucleus retroambiguus with
      lumbosacral projections in female cats.
AB  - Nucleus retroambiguus (NRA), in the caudal medulla, projects to all spinal
      levels. One physiological role is abdominal pressure control, evidenced by
      projections to intercostal and abdominal motoneurons from expiratory bulbospinal
      neurons (EBSNs) within NRA. The roles of NRA projections to the lumbosacral cord
      are less certain, although those to limb motoneurons may relate to mating
      behavior and those to Onuf's nucleus (ON) to maintaining continence. To clarify
      this we physiologically characterized NRA projections to the lumbosacral cord.
      Extracellular recordings were made in NRA under anesthesia and paralysis in
      estrus cats. Administered CO(2) gave a strong respiratory drive. Antidromic unit
      responses were recorded to stimulation of the contralateral ventrolateral
      funiculus of L(6), L(7), or sacral segments and to microstimulation in the region
      of semimembranosus motor nucleus or ON. All units were found at sites showing
      expiratory discharges. Units that showed collisions between antidromic and
      spontaneous spikes (all in late expiration) were identified as EBSNs. These were
      common from the ventrolateral funiculus (VLF) of L(6) (42.5%) or L(7) (32.9%),
      but rare from the sacral VLF or the motor nuclei. Antidromic latencies revealed a
      subthreshold respiratory drive in some non-EBSNs. This group had lower conduction
      velocities than the EBSNs. The remainder, with a negligible respiratory drive,
      had even lower conduction velocities. A new population of NRA neurons has thus
      been defined. They are not active even with a strong respiratory drive, but may
      provide most of the synaptic input from NRA to lower lumbar and sacral segments
      and could subserve functions related to mating behavior.

PMID- 15972830
TI  - Heterogeneity of voltage- and chemosignal-activated response profiles in
      vomeronasal sensory neurons.
AB  - Liolaemus lizards were explored to ascertain whether they would make an amenable
      model to study single-cell electrophysiology of neurons in the vomeronasal organ
      (VNO). Despite a rich array of chemosensory-related behaviors chronicled for this
      genus, no anatomical or functional data exist for the VNO, the organ mediating
      these types of behaviors. Two Liolaemus species (L. bellii and L. nigroviridis)
      were collected in Central Chile in the Farellones Mountains and transported to
      the United States. Lizards were subjected to hypothermia and then a lethal
      injection of sodium pentabarbitol prior to all experiments described in the
      following text. Retrograde dye perfusion combined with histological techniques
      demonstrated a compartmentalization of the proportionally large VNO from the main
      olfactory epithelium (MOE) in cryosections of L. bellii. SDS-PAGE analysis of the
      VNO of both species demonstrated the expression of three G protein subunits,
      namely, G(alphao), G(alphai2), and G(beta), and the absence of G(alphaolf),
      G(alpha11), and G(q), the latter of which are traditionally found in the MOE.
      Vomeronasal (VN) neurons were enzymatically isolated for whole cell voltage-clamp
      electrophysiology of single neurons. Both species demonstrated a tetrodotoxin
      (TTX)-sensitive, rapidly inactivating sodium current and a tetraethylammonium
      (TEA)-sensitive potassium current that had a transient and sustained component.
      VN neurons were classified into two types dependent on the ratio of sodium over
      sustained potassium current. VN neurons exhibited outward and inward chemosignal
      evoked currents when stimulated with pheromone-containing secretions taken from
      the feces, skin, and precloacal pores. Fifty-nine percent of the neurons were
      responsive to at least one compound when presented with a battery of five
      different secretions. The breadth of responsiveness (H metric) demonstrated a
      heterogeneous population of tuning with a mean of 0.29.

PMID- 15972832
TI  - Synaptically released and exogenous ACh activates different nicotinic receptors
      to enhance evoked glutamatergic transmission in the lateral geniculate nucleus.
AB  - The effects of activation of nicotinic acetylcholine receptors (nAChRs) on
      glutamatergic transmission in the ventral lateral geniculate nucleus (LGNv) were
      examined in chick brain slices. Whole cell recordings showed that monosynaptic
      postsynaptic currents (PSCs) evoked in LGNv neurons by optic tract stimulation
      were blocked by glutamate receptor antagonists. Exogenously applied nicotine (0.5
      microM), choline (1 mM), or acetylcholine (ACh, 100 microM) markedly increased
      (>3-fold) these evoked PSCs. Potentiation by ACh was dose-dependent and did not
      desensitize during a 5-min application. In a second set of experiments, the
      effect of releasing endogenous ACh by stimulating the lateral portion of the LGNv
      through a separate conditioning electrode before optic tract stimulation was
      examined. Conditioning stimulation trains increased PSCs by an average of 5.2
      fold, an effect dependent on both the intensity and number of conditioning
      pulses. This increase in PSC amplitude was most likely caused by released ACh
      activating alpha6- and/or alpha3-containing nAChRs because it was blocked by 100
      nM alpha-conotoxin MII, 100 nM dihydro-beta-erythroidine (DHbetaE), and 0.1-1.0
      microM methyllycaconitine (MLA). In contrast, exogenously applied ACh increased
      PSC amplitude by activating a pharmacologically different population of nAChRs
      because this effect was inhibited by 100 nM alpha-bungarotoxin, 50 nM MLA, and a
      high concentration (30 microM) of DHbetaE, indicating that alpha7- and/or alpha8
      containing receptors were involved. The results are consistent with a model
      whereby alpha6- and/or alpha3-containing nAChRs on retinal ganglion cell nerve
      terminals are located preferentially at cholinergic synapses, whereas alpha7-
      and/or alpha8-containing receptors are primarily extrasynaptic.

PMID- 15972833
TI  - Oscillations in the olfactory bulb carry information about odorant history.
AB  - While odorant-evoked oscillations in the vertebrate olfactory bulb have been
      studied extensively, information about their possible cognitive role has been
      missing. Using voltage-sensitive dye imaging, we show that repeated odorant
      presentations with interstimulus intervals of 2-12 s had dramatic and diverse
      effects on the three oscillations that occur in the turtle olfactory bulb. Two of
      the oscillations are strikingly depressed in response to the second stimulation
      even of a new odorant was presented. The third oscillation is enhanced if the
      odorant is the same but suppressed if the odorant is new. The effects suggest
      that the oscillations carry information about odorant novelty and consistency.

PMID- 15972835
TI  - Voluntary control of human jaw stiffness.
AB  - Recent studies of human arm movement have suggested that the control of stiffness
      may be important both for maintaining stability and for achieving differences in
      movement accuracy. In the present study, we have examined the voluntary control
      of postural stiffness in 3D in the human jaw. The goal is to address the possible
      role of stiffness control in both stabilizing the jaw and in achieving the
      differential precision requirements of speech sounds. We previously showed that
      patterns of kinematic variability in speech are systematically related to the
      stiffness of the jaw. If the nervous system uses stiffness control as a means to
      regulate kinematic variation in speech, it should also be possible to show that
      subjects can voluntarily modify jaw stiffness. Using a robotic device, a series
      of force pulses was applied to the jaw to elicit changes in stiffness to resist
      displacement. Three orthogonal directions and three magnitudes of forces were
      tested. In all conditions, subjects increased the magnitude of jaw stiffness to
      resist the effects of the applied forces. Apart from the horizontal direction,
      greater increases in stiffness were observed when larger forces were applied.
      Moreover, subjects differentially increased jaw stiffness along a vertical axis
      to counteract disturbances in this direction. The observed changes in the
      magnitude of stiffness in different directions suggest an ability to control the
      pattern of stiffness of the jaw. The results are interpreted as evidence that jaw
      stiffness can be adjusted voluntarily, and thus may play a role in stabilizing
      the jaw and in controlling movement variation in the orofacial system.

PMID- 15972834
TI  - Voltage-dependent calcium currents in trigeminal motoneurons of early postnatal
      rats: modulation by 5-HT receptors.
AB  - Trigeminal motoneurons relay the final output signals generated within the oral
      motor pattern generating circuit(s) to muscles for execution of various motor
      patterns. In recent years, these motoneurons were shown to possess voltage
      dependent nonlinear membrane properties that allow them to actively participate
      in sculpting their final output. A complete understanding of the factors
      controlling trigeminal motoneuronal (TMN) discharge during oral-motor activity
      requires, at a minimum, a detailed understanding of the palette of ion channels
      responsible for membrane excitability and a determination of whether these ion
      channels are targets for modulation. Toward that end, we studied in detail the
      properties of calcium channels in TMNs and their susceptibility to modulation by
      5-HT in rat brain slices. We found that based on pharmacological and voltage
      dependent properties, high-voltage-activated (HVA) N-type [omega-conotoxin GVIA
      (omega-CgTX)]-sensitive, and to a lesser extent P/Q-type [omega-agatoxin IVA
      (omega-Aga IVA)]-sensitive, calcium channels make up the majority of the whole
      cell calcium current. 5-HT (5.0 microM) decreased HVA current by 31.3 +/- 2.2%,
      and the majority of this suppression resulted from reduction of current flow
      through N- and P/Q-type calcium channels. In contrast, 5-HT had no effect on low
      voltage-activated (LVA) current amplitude in TMNs. HVA calcium current inhibition
      was mimicked by 5-CT, a 5-HT1 receptor agonist, and by R(+)-8
      hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), a specific 5-HT1A agonist.
      The effects of 5-HT were blocked by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4
      [4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) but not by ketanserin,
      a 5-HT(2/1C) antagonist. Under current clamp, omega-CgTX and 5-HT were most
      effective in suppressing the mAHP and both increased the spike frequency and
      input/output gain in response to current injection. Calcium current modulation by
      5-HT1A receptors likely is an important mechanism to fine tune the input/output
      gain of TMNs in response to small incoming synaptic inputs and accounts for some
      of the previously reported effects of 5-HT on TMN excitability during tonic and
      burst activity during oral-motor behavior.

PMID- 15972836
TI  - Similarity of direction tuning among responses to stimulation of different
      whiskers in neurons of rat barrel cortex.
AB  - Cells in the rat barrel cortex exhibit stimulus-specific response properties. To
      understand the network mechanism of direction selectivity in response to facial
      whisker deflection, we examined direction selectivity of neuronal responses to
      single- and multi-whisker stimulations. In the case of regular-spiking units,
      i.e., putative excitatory cells, direction preferences were quite similar between
      responses to single-whisker stimulation of the principal and adjacent whiskers.
      In multi-whisker stimulation at short (< or = 5 ms) interstimulus intervals
      (ISIs), response facilitation was evoked only when the whiskers were deflected to
      the preferred direction of the response to the single whisker stimulation. These
      results suggest that there are neuronal networks among cells with different
      whisker preferences but with a common direction preference that could be the
      neuronal basis of the direction-selective facilitation of the response to multi
      whisker stimulation. In contrast, multi-whisker stimulation at long (> or = 6 ms)
      ISIs caused non-direction-selective suppression of the response to the second
      stimulus. In the case of fast-spiking units, i.e., putative inhibitory cells,
      poor direction selectivity was exhibited. Thus stimulus direction is represented
      as the direction-selective responses to the single- and multi-whisker
      stimulations of putative excitatory cells rather than those of putative
      inhibitory cells.

PMID- 15972837
TI  - Target-specific short-term dynamics are important for the function of synapses in
      an oscillatory neural network.
AB  - Short-term dynamics such as facilitation and depression are present in most
      synapses and are often target-specific even for synapses from the same type of
      neuron. We examine the dynamics and possible functions of two synapses from the
      same presynaptic neuron in the rhythmically active pyloric network of the spiny
      lobster. Using simultaneous recordings, we show that the synapses from the
      lateral pyloric (LP) neuron to the pyloric dilator (PD; a member of the pyloric
      pacemaker ensemble) and the pyloric constrictor (PY) neurons both show short-term
      depression. However, the postsynaptic potentials produced by the LP-to-PD synapse
      are larger in amplitude, depress less, and recover faster than those produced by
      the LP-to-PY synapse. The main function of the LP-to-PD synapse is to slow down
      the pyloric rhythm. However, in some cases, it slows down the rhythm only when it
      is fast and has no effect or to speeds up when it is slow. In contrast, the LP-to
      PY synapse functions to delay the activity of the PY neuron; this delay increases
      as the cycle period becomes longer. Using a computational model, we show that the
      short-term dynamics of synaptic depression observed for each of these synapses
      are tailored to their individual functions and that replacing the dynamics of
      either synapse with the other would disrupt these functions. Together, the
      experimental and modeling results suggest that the target-specific features of
      short-term synaptic depression are functionally important for synapses efferent
      from the same presynaptic neuron.

PMID- 15972838
TI  - Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations
      thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of
      endothelial cells in vitro.
AB  - Endothelial cells actively participate in inflammatory events by regulating
      leukocyte recruitment via the expression of inflammatory genes such as E
      selectin, VCAM-1, ICAM-1, IL-6, IL-8, and cyclooxygenase (COX)-2. In this study
      we showed by real-time RT-PCR that activation of human umbilical vein endothelial
      cells (HUVEC) by TNF-alpha and IL-1beta differentially affected the expression of
      these inflammatory genes. Combined treatment with TNF-alpha and IL-1beta resulted
      in nonadditive, additive, and even synergistic induction of expression of VCAM-1,
      IL-8, and IL-6, respectively. Overexpression of dominant-negative inhibitor
      kappaB protein blocking NF-kappaB signaling confirmed a major role of this
      pathway in controlling both TNF-alpha- and IL-1beta-induced expression of most of
      the genes studied. Although dexamethasone exerted limited effects at 1 muM, the
      thioredoxin inhibitor MOL-294, which regulates the redox state of NF-kappaB,
      mainly inhibited adhesion molecule expression. Its most pronounced effect was
      seen on VCAM-1 mRNA levels, especially in IL-1beta-activated endothelium. One
      micromolar RWJ-67657, an inhibitor of p38 MAPK activity, diminished TNF-alpha-
      and IL-1beta-induced expression of IL-6, IL-8, and E-selectin but had little
      effect on VCAM-1 and ICAM-1. Combined treatment of HUVEC with MOL-294 and RWJ
      67657 resulted in significant blocking of the expression of E-selectin, IL-6, IL
      8, and COX-2. The inhibitory effects were much stronger than those observed with
      single drug treatment. Application of combinations of drugs that affect multiple
      targets in activated endothelial cells may therefore be considered as a potential
      new therapeutic strategy to inhibit inflammatory disease activity.

PMID- 15972839
TI  - Age-related apoptotic responses to stretch-induced hypertrophy in quail slow
      tonic skeletal muscle.
AB  - In the present study, we examined the responses of apoptosis and apoptotic
      regulatory factors to muscle hypertrophy induced by stretch overload in quail
      slow-tonic muscles. The wings from one side of young and aged Japanese quails
      were loaded by attaching a tube weight corresponding to 12% of the bird's body
      weight for 7 or 21 days. Muscle from the contralateral side served as the
      intraanimal control. Relative to the intraanimal contralateral control side, the
      muscle wet weight increased by 96% in young birds, whereas the muscle weight gain
      in aged birds was not significant after 7 days of loading. After 21 days of
      loading, muscle weight significantly increased by 179% and 102% in young and aged
      birds, respectively. Heat shock protein (HSP)72 and HSP27 protein contents in the
      loaded sides were higher than on the control sides exclusively in young birds
      after 7 days of loading. Compared with the contralateral control muscle, the
      extent of apoptotic DNA fragmentation and the total cytosolic apoptosis-inducing
      factor protein content were reduced in all loaded muscles except for the 7-day
      loaded muscles from the aged birds. Bax protein content was diminished in the
      loaded muscle relative to the control side from all groups, whereas Bcl-2 protein
      content was reduced in the young and aged muscles after 21 days of loading. The
      total cytosolic cytochrome c protein content was decreased and the X chromosome
      linked inhibitor of apoptosis protein content was elevated in 7- and 21-day
      loaded muscles relative to the intraanimal control muscle from young birds.
      Furthermore, after 7 days of loading the muscles of aged birds, H(2)O(2) content
      and the total cytosolic protein content of second mitochondrial activator of
      caspases/direct inhibitor of apoptosis-binding protein with low isoelectric point
      were elevated compared with the intraanimal control side. These data suggest that
      stretch overload-induced muscle hypertrophy is associated with changes in
      apoptosis in slow-tonic skeletal muscle. Moreover, discrepant apoptotic responses
      to muscle overload in young and aged muscles may account in part for the age
      related decline in the capability for muscle hypertrophy.

PMID- 15972840
TI  - Hypothermia enhances phosphorylation of I{kappa}B kinase and prolongs nuclear
      localization of NF-{kappa}B in lipopolysaccharide-activated macrophages.
AB  - Hypothermia (HT) has been associated with both beneficial and detrimental
      consequences in various pathophysiological states. While HT is generally thought
      to have anti-inflammatory and cytoprotective effects, we have previously shown
      that moderate in vitro HT prolongs TNF-alpha production by LPS-stimulated
      mononuclear phagocytes, in part by prolonging TNF-alpha gene transcription and
      activation of the pleiotropic transcription factor NF-kappaB. In this study, we
      have further characterized the effect of moderate (32 degrees C) and marked (28
      degrees C) HT in human monocytic THP-1 cells by showing that even short (2 h)
      exposure to HT followed by a return to normothermic conditions for 22 h resulted
      in augmented and prolonged production of TNF-alpha. Production of heat shock
      protein 72 and activation of heat shock factor 1 are not affected by HT in these
      studies, suggesting that the effect is not part of a generalized stress response.
      Using immunoblotting, we have shown that HT augments phosphorylation of IKK-beta
      and IKK-alpha (up to an 8-fold increase at 28 degrees C and a 3.6-fold increase
      at 32 degrees C vs. 37 degrees C). Furthermore, nuclear accumulation of NF-kappaB
      p65 was significantly prolonged in hypothermic cells (1.4- and 2.5-fold more
      nuclear p65 at 2 and 4 h at 28 vs. 37 degrees C). Reexpression of IkappaB-alpha,
      which contributes to the termination of NF-kappaB-dependent transcription, was
      delayed several hours in HT-exposed cells. Thus we have shown that clinically
      relevant HT alters both cytosolic and nuclear events responsible for NF-kappaB
      activation and deactivation. Enhanced NF-kappaB activation may contribute to the
      immunomodulatory effects of HT in various clinical settings.

PMID- 15972843
TI  - Practice parameter: therapies for essential tremor: report of the Quality
      Standards Subcommittee of the American Academy of Neurology.
AB  - BACKGROUND: Essential tremor (ET) is one of the most common tremor disorders in
      adults and is characterized by kinetic and postural tremor. To develop this
      practice parameter, the authors reviewed available evidence regarding initiation
      of pharmacologic and surgical therapies, duration of their effect, their relative
      benefits and risks, and the strength of evidence supporting their use. METHODS: A
      literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was
      performed to identify clinical trials in patients with ET published between 1966
      and August 2004. Articles were classified according to a four-tiered level of
      evidence scheme and recommendations were based on the level of evidence. RESULTS
      AND CONCLUSIONS: Propranolol and primidone reduce limb tremor (Level A).
      Alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are
      probably effective in reducing limb tremor (Level B). Limited studies suggest
      that propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol,
      and nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may
      reduce hand tremor but is associated with dose-dependent hand weakness (Level C).
      Botulinum toxin A may reduce head tremor (Level C) and voice tremor (Level C),
      but breathiness, hoarseness, and swallowing difficulties may occur in the
      treatment of voice tremor. Chronic deep brain stimulation (DBS) (Level C) and
      thalamotomy (Level C) are highly efficacious in reducing tremor. Each procedure
      carries a small risk of major complications. Some adverse events from DBS may
      resolve with time or with adjustment of stimulator settings. There is
      insufficient evidence regarding the surgical treatment of head and voice tremor
      and the use of gamma knife thalamotomy (Level U). Additional prospective, double
      blind, placebo-controlled trials are needed to better determine the efficacy and
      side effects of pharmacologic and surgical treatments of ET.

PMID- 15972844
TI  - Spliced-leader trans-splicing in freshwater planarians.
AB  - trans-Splicing, in which a spliced-leader (SL) RNA is appended to the most 5'
      exon of independently transcribed pre-mRNAs, has been described in a wide range
      of eukaryotes, from protozoans to chordates. Here we describe trans-splicing in
      the freshwater planarian Schmidtea mediterranea, a free-living member of the
      phylum Platyhelminthes. Analysis of an expressed sequence tag (EST) collection
      from this organism showed that over 300 transcripts shared one of two
      approximately 35-base sequences (Smed SL-1 and SL-2) at their 5' ends.
      Examination of genomic sequences encoding representatives of these transcripts
      revealed that these shared sequences were transcribed elsewhere in the genome.
      RNA blot analysis, 5' and 3' rapid amplification of cDNA ends, as well as genomic
      sequence data showed that 42-nt SL sequences were derived from small RNAs of
      approximately 110 nt. Similar sequences were also found at the 5' ends of ESTs
      from the planarian Dugesia japonica. trans-Splicing has already been described in
      numerous representatives of the phylum Platyhelminthes (trematodes, cestodes, and
      polyclads); its presence in two representatives of the triclads supports the
      hypothesis that this mode of RNA processing is ancestral within this group. The
      upcoming complete genome sequence of S. mediterranea, combined with this animal's
      experimental accessibility and susceptibility to RNAi, provide another model
      organism in which to study the function of the still-enigmatic trans-splicing.

PMID- 15972845
TI  - Molecular evolution of rickettsia surface antigens: evidence of positive
      selection.
AB  - The Rickettsia genus is a group of obligate intracellular parasitic alpha
      proteobacteria that includes human pathogens responsible for the typhus disease
      and various types of spotted fevers. rOmpA and rOmpB are two members of the
      "surface cell antigen" (Sca) autotransporter (AT) protein family that may play
      key roles in the adhesion of the Rickettsia cells to the host tissue. These
      molecules are likely determinants for the pathogenicity of the Rickettsia and
      represent good candidates for vaccine development. We identified the 17 members
      of this family of outer-membrane proteins in nine fully sequenced Rickettsia
      genomes. The typical architecture of the Sca proteins is composed of an N
      terminal signal peptide and a C-terminal AT domain that promote the export of the
      central passenger domain to the outside of the bacteria. A characteristic of this
      family is the frequent degradation of the genes, which results in different
      subsets of the sca genes being expressed among Rickettsia species. Here, we
      present a detailed analysis of their phylogenetic relationships and evolution. We
      provide strong evidence that rOmpA and rOmpB as well as three other members of
      the Sca protein family--Sca1, Sca2, and Sca4--have evolved under positive
      selection. The exclusive distribution of the predicted positively selected sites
      within the passenger domains of these proteins argues that these regions are
      involved in the interaction with the host and may be locked in "arms race"
      coevolutionary conflicts.

PMID- 15972846
TI  - Gene conversion drives the evolution of HINTW, an ampliconic gene on the female
      specific avian W chromosome.
AB  - The HINTW gene on the female-specific W chromosome of chicken and other birds is
      amplified and present in numerous copies. Moreover, as HINTW is distinctly
      different from its homolog on the Z chromosome (HINTZ), is a candidate gene in
      avian sex determination, and evolves rapidly under positive selection, it shows
      several common features to ampliconic and testis-specific genes on the mammalian
      Y chromosome. A phylogenetic analysis within galliform birds (chicken, turkey,
      quail, and pheasant) shows that individual HINTW copies within each species are
      more similar to each other than to gene copies of related species. Such
      convergent evolution is most easily explained by recurrent events of gene
      conversion, the rate of which we estimated at 10(-6)-10(-5) per site and
      generation. A significantly higher GC content of HINTW than of other W-linked
      genes is consistent with biased gene conversion increasing the fixation
      probability of mutations involving G and C nucleotides. Furthermore, and as a
      likely consequence, the neutral substitution rate is almost twice as high in
      HINTW as in other W-linked genes. The region on W encompassing the HINTW gene
      cluster is not covered in the initial assembly of the chicken genome, but
      analysis of raw sequence reads indicates that gene copy number is significantly
      higher than a previous estimate of 40. While sexual selection is one of several
      factors that potentially affect the evolution of ampliconic, male-specific genes
      on the mammalian Y chromosome, data from HINTW provide evidence that gene
      amplification followed by gene conversion can evolve in female-specific
      chromosomes in the absence of sexual selection. The presence of multiple and
      highly similar copies of HINTW may be related to protein function, but, more
      generally, amplification and conversion offers a means to the avoidance of
      accumulation of deleterious mutations in nonrecombining chromosomes.

PMID- 15972847
TI  - Entropy and GC Content in the beta-esterase gene cluster of the Drosophila
      melanogaster subgroup.
AB  - We perform spectral entropy and GC content analyses in the beta-esterase gene
      cluster, including the Est-6 gene and the psiEst-6 putative pseudogene, in seven
      species of the Drosophila melanogaster species subgroup. psiEst-6 combines
      features of functional and nonfunctional genes. The spectral entropies show
      distinctly lower structural ordering for psiEst-6 than for Est-6 in all species
      studied. Our observations agree with previous results for D. melanogaster and
      provide additional support to our hypothesis that after the duplication event Est
      6 retained the esterase-coding function and its role during copulation, while
      psiEst-6 lost that function but now operates in conjunction with Est-6 as an
      intergene. Entropy accumulation is not a completely random process for either
      gene. Structural entropy is nucleotide dependent. The relative normalized
      deviations for structural entropy are higher for G than for C nucleotides. The
      entropy values are similar for Est-6 and psiEst-6 in the case of A and T but are
      lower for Est-6 in the case of G and C. The GC content in synonymous positions is
      uniformly higher in Est-6 than in psiEst-6, which agrees with the reduced GC
      content generally observed in pseudogenes and nonfunctional sequences. The
      observed differences in entropy and GC content reflect an evolutionary shift
      associated with the process of pseudogenization and subsequent functional
      divergence of psiEst-6 and Est-6 after the duplication event.

PMID- 15972848
TI  - Sequence evidence for sporadic intergeneric DNA introgression from wheat into a
      wild Aegilops species.
AB  - Introgressive hybridization has played a crucial role in the evolution of many
      plant species, especially polyploids. The duplicated genetic material and wide
      geographical distribution facilitate hybridization and introgression among
      polyploid species having either homologous or homoeologous genomes. Such
      introgression may lead to the production of recombinant genomes that are more
      difficult to form at the diploid level. Crop genes that have introgressed into
      wild relatives can increase the capability of the wild relatives to adapt to
      agricultural environments and compete with crops or to compete with other wild
      species. Although the transfer of genes from crops into their conspecific
      immediate wild progenitors has been reported, little is known about spontaneous
      gene movement from crops to more distantly related species. We describe recent
      spontaneous DNA introgression from domesticated polyploid wheat into distantly
      related, wild tetraploid Aegilops peregrina (syn. Aegilops variabilis) and the
      stabilization of this sequence in wild populations despite not having homologous
      chromosomes. Our results show that DNA can spontaneously introgress between
      homoeologous genomes of species of the tribe Triticeae and, in the case of crop
      wild relatives, possibly enrich the wild population. These results also emphasize
      the need for fail-safe mechanisms in transgenic crops to prevent gene flow where
      there may be ecological risks.

PMID- 15972849
TI  - Crk-associated substrate tyrosine phosphorylation sites are critical for invasion
      and metastasis of SRC-transformed cells.
AB  - Crk-associated substrate (CAS, p130Cas) is a major tyrosine phosphorylated
      protein in cells transformed by v-crk and v-src oncogenes. We recently reported
      that reexpression of CAS in CAS-deficient mouse embryo fibroblasts transformed by
      oncogenic Src promoted an invasive phenotype associated with enhanced cell
      migration through Matrigel, organization of actin into large podosome ring and
      belt structures, activation of matrix metalloproteinase-2, and elevated tyrosine
      phosphorylation of the focal adhesion proteins FAK and paxillin. We have now
      extended these studies to examine the mechanism by which CAS achieves these
      changes and to evaluate the potential role for CAS in promoting in vivo tumor
      growth and metastasis. Whereas the presence or absence of CAS did not alter the
      primary growth of subcutaneous-injected Src-transformed mouse embryo fibroblasts,
      CAS expression was required to promote lung metastasis following removal of the
      primary tumor. The substrate domain YxxP tyrosines, the major sites of CAS
      phosphorylation by Src that mediate interactions with Crk, were found to be
      critical for promoting both invasive and metastatic properties of the cells. The
      ability of CAS to promote Matrigel invasion, formation of large podosome
      structures, and tyrosine phosphorylation of Src substrates, including FAK,
      paxillin, and cortactin, was also strictly dependent on the YxxP tyrosines. In
      contrast, matrix metalloproteinase-2 activation was most dependent on the CAS SH3
      domain, whereas the substrate domain YxxP sites also contributed to this
      property. Thus multiple CAS-mediated signaling events are implicated in promoting
      invasive and metastatic properties of Src-transformed cells.

PMID- 15972850
TI  - Vitamin k epoxide reductase: a protein involved in angiogenesis.
AB  - Vitamin K epoxide reductase (VKOR) is a newly identified protein which has been
      reported to convert the epoxide of vitamin K back to vitamin K, a cofactor
      essential for the posttranslational gamma-carboxylation of several blood
      coagulation factors. We found that the gene is expressed ubiquitously including
      vascular endothelial cells, smooth muscle cells, fibroblasts and cardiomyocytes,
      and is overexpressed in 11 tumor tissues on microarray. Stable transfection of
      VKOR cDNA into tumor cell line A549 and H7402 did not promote the cell
      proliferation. These results promoted us to hypothesize that VKOR may also be
      involved in angiogenesis. To test this hypothesis, the expression of VKOR was
      studied in different vascular cells in developmental and pathologic heart
      tissues. The effects of overexpression and suppressing expression of VKOR on
      endothelial cell proliferation, migration, adhesion, and tubular network
      formation were explored. We found that VKOR expression in arteries was prominent
      in vascular endothelial cells and was high in the ventricular aneurysm tissue of
      human heart and human fetal heart. In vitro studies showed that overexpression of
      VKOR slightly but significantly stimulated human umbilical vein endothelial cell
      proliferation (by 120%), migration (by 118%), adhesion (by 117%), as well as
      tubular network formation. Antisense to VKOR gene inhibited the proliferation (by
      67%), migration (by 64%), adhesion (by 50%), and tubular network formation. Our
      findings support the impact of VKOR in the process of angiogenesis; hence, the
      molecule may have a potential application in cardiovascular disease and cancer
      therapy.

PMID- 15972851
TI  - Methylation silencing of the Apaf-1 gene in acute leukemia.
AB  - Apaf-1 is important for tumor suppression and drug resistance because it plays a
      central role in DNA damage-induced apoptosis. Inactivation of the Apaf-1 gene is
      implicated in disease progression and chemoresistance of some malignancies. In
      this study, we attempted to clarify the role of Apaf-1 in leukemogenesis. Apaf-1
      mRNA levels were below the detection limit or very low in 5 of 20 human leukemia
      cell lines (25%) and 5 of 12 primary acute myeloblastic leukemia cells (42%).
      There were no gross structural abnormalities in the Apaf-1 gene in these samples.
      Expression of factors regulating Apaf-1 transcription, such as E2F-1, p53, and Sp
      1, did not differ between Apaf-1-positive and Apaf-1-negative cells. Methylation
      of CpG in the region between +87 and +128 of the Apaf-1 gene was almost
      exclusively observed in Apaf-1-defective cell lines. Treatment of these cells
      with 5-aza-2'-deoxycytidine, a specific inhibitor of DNA methylation, restored
      the expression of Apaf-1. Furthermore, we showed that the region between +87 and
      +128 could act as a repressor element by recruiting corepressors such as
      methylated DNA-binding domain 2 and histone deacetylase 1 upon methylation.
      Overexpression of Dnmt1, a mammalian maintenance DNA methyltransferase, was
      associated with Apaf-1 gene methylation. DNAs from Dnmt1-overexpressing cells
      were more resistant to digestion with methylation-sensitive enzyme HpaII than
      those from cells with low Dnmt1 expression, suggesting that Dnmt1 mediates
      aberrant methylation of multiple genes. In conclusion, methylation silencing is a
      mechanism of the inactivation of Apaf-1 in acute leukemia, and Dnmt1
      overexpression may underlie hypermethylation of the Apaf-1 gene.

PMID- 15972852
TI  - Contribution of epigenetic silencing of tumor necrosis factor-related apoptosis
      inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer.
AB  - Dysregulation of apoptosis may support tumorigenesis by allowing cells to live
      beyond their normally intended life span. The various receptors for tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) are located on
      chromosome 8p21.2, a region frequently deleted in ovarian cancer. Lack of
      expression of TRAIL receptor 1 (death receptor 4, DR4) correlates with resistance
      to TRAIL-induced apoptosis in ovarian cancer cells. Reconstitution of DR4 in the
      TRAIL-resistant A2780 ovarian cancer cell line was investigated with the
      demethylating agent 5-aza-2'-deoxycytidine and transient gene transfer.
      Regulation of other genes in the TRAIL pathway by 5-aza-2'-deoxycytidine was
      assessed in DNA GeneChip experiments. Primary ovarian cancers were analyzed by
      methylation-specific PCR and immunohistochemical analysis of a tissue microarray.
      Regulation of DR4 expression by demethylation or transient transfection is of
      functional relevance for TRAIL resistance in an ovarian cancer cell line.
      Hypermethylation of the DR4 promoter could be found in 10 of 36 (27.7%) DNAs
      isolated from ovarian cancer tissue. In an independent set of 68 ovarian cancer
      cases, a complete loss or down-regulation of DR4 protein expression was observed
      10.3% and 8.8% patients, respectively. A significant (P = 0.019) majority of
      these patients was below 50 years of age. Our findings show a functional
      relevance of the level of DR4 expression in ovarian cancer and suggest a
      substantial contribution of DR4 hypermethylation and consequent loss of DR4
      expression to ovarian cancer pathogenesis, particularly in premenopausal
      patients.

PMID- 15972853
TI  - Enhanced G2-M arrest by nuclear factor-{kappa}B-dependent p21waf1/cip1 induction.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) regulates cell
      survival pathways, but the molecular mechanisms involved are not completely
      understood. Here, we developed a NF-kappaB reporter cell system derived from CEM
      T leukemic cells to monitor the consequences of NF-kappaB activation following
      DNA damage insults. Cells that activated NF-kappaB in response to ionizing
      radiation or etoposide arrested in the G2-M phase for a prolonged time, which was
      followed by increased cell cycle reentry and survival. In contrast, those that
      failed to activate NF-kappaB underwent transient G2-M arrest and extensive cell
      death. Importantly, p21waf1/cip1 was induced in S-G2-M phases in a NF-kappaB
      dependent manner, and RNA interference of this cell cycle regulator reduced the
      observed NF-kappaB-dependent phenotypes. Thus, cell cycle-coupled induction of
      p21waf1/cip1 by NF-kappaB represents a resistance mechanism in certain cancer
      cells.

PMID- 15972854
TI  - Phosphorylations of DEAD box p68 RNA helicase are associated with cancer
      development and cell proliferation.
AB  - The nuclear p68 RNA helicase is essential for normal cell growth. The protein
      plays a very important role in early organ development and maturation. In our
      previous report, we showed that recombinant p68 RNA helicase was phosphorylated
      at serine/threonine and tyrosine residue(s). In the present study, we examined
      the phosphorylation status of p68 in six different cancer cell lines and compared
      the results with those in cells derived from the corresponding normal tissues. We
      showed here that p68 was phosphorylated at tyrosine residue(s) in all tested
      cancer cells but not in the corresponding normal cells/tissues. The tyrosyl
      phosphorylation of p68 also responded to platelet-derived growth factor. It is
      thus clear that p68 phosphorylation at tyrosine residue(s) is associated with
      abnormal cell proliferation and cancer development. The tyrosyl
      phosphorylation(s) was diminished if the cancer cells were treated with apoptosis
      agents, such as tumor necrosis factor-alpha, tumor necrosis factor-related
      apoptosis-inducer ligand, and STI-571. The tyrosyl phosphorylation of p68,
      however, was not affected by other anticancer drugs, such as piceatannol,
      etoposide, and taxol. The close correlation between p68 phosphorylations and
      cancer may provide a useful diagnostic marker and potential therapeutic target
      for cancer treatment.

PMID- 15972855
TI  - MutS inhibits RecA-mediated strand transfer with methylated DNA substrates.
AB  - DNA mismatch repair (MMR) sensitizes human and Escherichia coli dam cells to the
      cytotoxic action of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) while abrogation
      of such repair results in drug resistance. In DNA methylated by MNNG, MMR action
      is the result of MutS recognition of O6-methylguanine base pairs. MutS and Ada
      methyltransferase compete for the MNNG-induced O6-methylguanine residues, and MMR
      induced cytotoxicity is abrogated when Ada is present at higher concentrations
      than normal. To test the hypothesis that MMR sensitization is due to decreased
      recombinational repair, we used a RecA-mediated strand exchange assay between
      homologous phiX174 substrate molecules, one of which was methylated with MNNG.
      MutS inhibited strand transfer on such substrates in a concentration-dependent
      manner and its inhibitory effect was enhanced by MutL. There was no effect of
      these proteins on RecA activity with unmethylated substrates. We quantified the
      number of O6-methylguanine residues in methylated DNA by HPLC-MS/MS and 5-10 of
      these residues in phiX174 DNA (5386 bp) were sufficient to block the RecA
      reaction in the presence of MutS and MutL. These results are consistent with a
      model in which methylated DNA is perceived by the cell as homeologous and
      prevented from recombining with homologous DNA by the MMR system.

PMID- 15972856
TI  - Identification of novel restriction endonuclease-like fold families among
      hypothetical proteins.
AB  - Restriction endonucleases and other nucleic acid cleaving enzymes form a large
      and extremely diverse superfamily that display little sequence similarity despite
      retaining a common core fold responsible for cleavage. The lack of significant
      sequence similarity between protein families makes homology inference a
      challenging task and hinders new family identification with traditional sequence
      based approaches. Using the consensus fold recognition method Meta-BASIC that
      combines sequence profiles with predicted protein secondary structure, we
      identify nine new restriction endonuclease-like fold families among previously
      uncharacterized proteins and predict these proteins to cleave nucleic acid
      substrates. Application of transitive searches combined with gene neighborhood
      analysis allow us to confidently link these unknown families to a number of known
      restriction endonuclease-like structures and thus assign folds to the
      uncharacterized proteins. Finally, our method identifies a novel restriction
      endonuclease-like domain in the C-terminus of RecC that is not detected with
      structure-based searches of the existing PDB database.

PMID- 15972857
TI  - A T-stem slip in human mitochondrial tRNALeu(CUN) governs its charging capacity.
AB  - The human mitochondrial tRNALeu(CUN) [hmtRNALeu(CUN)] corresponds to the most
      abundant codon for leucine in human mitochondrial protein genes. Here, in vitro
      studies reveal that the U48C substitution in hmtRNALeu(CUN), which corresponds to
      the pathological T12311C gene mutation, improved the aminoacylation efficiency of
      hmtRNALeu(CUN). Enzymatic probing suggested a more flexible secondary structure
      in the wild-type hmtRNALeu(CUN) transcript compared with the U48C mutant.
      Structural analysis revealed that the flexibility of hmtRNALeu(CUN) facilitates a
      T-stem slip resulting in two potential tertiary structures. Several rationally
      designed tRNALeu(CUN) mutants were generated to examine the structural and
      functional consequences of the T-stem slip. Examination of these hmtRNALeu(CUN)
      mutants indicated that the T-stem slip governs tRNA accepting activity. These
      results suggest a novel, self-regulation mechanism of tRNA structure and
      function.

PMID- 15972858
TI  - Doctors and interrogators at Guantanamo Bay.

PMID- 15972859
TI  - Images in clinical medicine. Tsunami sinusitis.

PMID- 15972860
TI  - Marburg and Ebola--arming ourselves against the deadly filoviruses.

PMID- 15972861
TI  - Torcetrapib and atorvastatin--should marketing drive the research agenda?

PMID- 15972862
TI  - The lessons of Vioxx--drug safety and sales.

PMID- 15972863
TI  - Tailoring arthritis therapy in the wake of the NSAID crisis.

PMID- 15972864
TI  - Sudden death in patients with myocardial infarction and left ventricular
      dysfunction, heart failure, or both.
AB  - BACKGROUND: The risk of sudden death from cardiac causes is increased among
      survivors of acute myocardial infarction with reduced left ventricular systolic
      function. We assessed the risk and time course of sudden death in high-risk
      patients after myocardial infarction. METHODS: We studied 14,609 patients with
      left ventricular dysfunction, heart failure, or both after myocardial infarction
      to assess the incidence and timing of sudden unexpected death or cardiac arrest
      with resuscitation in relation to the left ventricular ejection fraction.
      RESULTS: Of 14,609 patients, 1067 (7 percent) had an event a median of 180 days
      after myocardial infarction: 903 died suddenly, and 164 were resuscitated after
      cardiac arrest. The risk was highest in the first 30 days after myocardial
      infarction--1.4 percent per month (95 percent confidence interval, 1.2 to 1.6
      percent)--and decreased to 0.14 percent per month (95 percent confidence
      interval, 0.11 to 0.18 percent) after 2 years. Patients with a left ventricular
      ejection fraction of 30 percent or less were at highest risk in this early period
      (rate, 2.3 percent per month; 95 percent confidence interval, 1.8 to 2.8
      percent). Nineteen percent of all sudden deaths or episodes of cardiac arrest
      with resuscitation occurred within the first 30 days after myocardial infarction,
      and 83 percent of all patients who died suddenly did so in the first 30 days
      after hospital discharge. Each decrease of 5 percentage points in the left
      ventricular ejection fraction was associated with a 21 percent adjusted increase
      in the risk of sudden death or cardiac arrest with resuscitation in the first 30
      days. CONCLUSIONS: The risk of sudden death is highest in the first 30 days after
      myocardial infarction among patients with left ventricular dysfunction, heart
      failure, or both. Thus, earlier implementation of strategies for preventing
      sudden death may be warranted in selected patients.

PMID- 15972865
TI  - Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung
      cancer.
AB  - BACKGROUND: We undertook to determine whether adjuvant vinorelbine plus cisplatin
      prolongs overall survival among patients with completely resected early-stage non
      small-cell lung cancer. METHODS: We randomly assigned patients with completely
      resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus
      cisplatin or to observation. The primary end point was overall survival;
      principal secondary end points were recurrence-free survival and the toxicity and
      safety of the regimen. RESULTS: A total of 482 patients underwent randomization
      to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of
      the patients had pathological stage IB disease and 55 percent had stage II, and
      all had an Eastern Cooperative Oncology Group performance status score of 0 or 1.
      In both groups, the median age was 61 years, 65 percent were men, and 53 percent
      had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients
      (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects
      in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were
      fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent),
      vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent),
      but severe (grade 3 or greater) toxic effects were uncommon (<10 percent).
      Overall survival was significantly prolonged in the chemotherapy group as
      compared with the observation group (94 vs. 73 months; hazard ratio for death,
      0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard
      ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent
      and 54 percent, respectively (P=0.03). CONCLUSIONS: Adjuvant vinorelbine plus
      cisplatin has an acceptable level of toxicity and prolongs disease-free and
      overall survival among patients with completely resected early-stage non-small
      cell lung cancer.

PMID- 15972866
TI  - Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that
      leads to a major loss of insulin-secreting beta cells. The further decline of
      beta-cell function after clinical onset might be prevented by treatment with CD3
      monoclonal antibodies, as suggested by the results of a phase 1 study. To provide
      proof of this therapeutic principle at the metabolic level, we initiated a phase
      2 placebo-controlled trial with a humanized antibody, an aglycosylated human IgG1
      antibody directed against CD3 (ChAglyCD3). METHODS: In a multicenter study, 80
      patients with new-onset type 1 diabetes were randomly assigned to receive placebo
      or ChAglyCD3 for six consecutive days. Patients were followed for 18 months,
      during which their daily insulin needs and residual beta-cell function were
      assessed according to glucose-clamp-induced C-peptide release before and after
      the administration of glucagon. RESULTS: At 6, 12, and 18 months, residual beta
      cell function was better maintained with ChAglyCD3 than with placebo. The insulin
      dose increased in the placebo group but not in the ChAglyCD3 group. This effect
      of ChAglyCD3 was most pronounced among patients with initial residual beta-cell
      function at or above the 50th percentile of the 80 patients. In this subgroup,
      the mean insulin dose at 18 months was 0.22 IU per kilogram of body weight per
      day with ChAglyCD3, as compared with 0.61 IU per kilogram with placebo (P<0.001).
      In this subgroup, 12 of 16 patients who received ChAglyCD3 (75 percent) received
      minimal doses of insulin (< or =0.25 IU per kilogram per day) as compared with
      none of the 21 patients who received placebo. Administration of ChAglyCD3 was
      associated with a moderate "flu-like" syndrome and transient symptoms of Epstein
      Barr viral mononucleosis. CONCLUSIONS: Short-term treatment with CD3 antibody
      preserves residual beta-cell function for at least 18 months in patients with
      recent-onset type 1 diabetes.

PMID- 15972868
TI  - Vertebrobasilar disease.

PMID- 15972869
TI  - Images in clinical medicine. Mixed cryoglobulinemia.

PMID- 15972867
TI  - Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3.
AB  - BACKGROUND: We hypothesized that in patients with hepatitis C virus (HCV)
      genotype 2 or 3 in whom HCV RNA is not detectable after 4 weeks of therapy, 12
      weeks of treatment is as effective as 24 weeks. METHODS: A total of 283 patients
      were randomly assigned to a standard 24-week regimen of peginterferon alfa-2b at
      a dose of 1.0 mug per kilogram weekly plus ribavirin at a dose of 1000 mg or 1200
      mg daily, on the basis of body weight. Of these, 70 patients were assigned to the
      24-week regimen (standard-duration group) and 213 patients to a variable regimen
      (variable-duration group) of 12 or 24 weeks, depending on whether tests for HCV
      RNA were negative or positive at week 4. The primary end point was HCV that was
      not detectable by polymerase-chain-reaction (PCR) assay 24 weeks after the
      completion of therapy. RESULTS: In the standard-duration group, 45 (64 percent)
      patients had HCV that was not detectable by PCR assay at week 4, as compared with
      133 (62 percent) in the variable-duration group (difference [the rate in the
      standard-duration group minus that in the variable-duration group], 2 percent; 95
      percent confidence interval, -11 to 15 percent). Fifty-three patients (76
      percent) in the standard-duration group and 164 patients (77 percent) in the
      variable-duration group had a sustained virologic response (difference, -1
      percent; 95 percent confidence interval, -13 to 10 percent). Fewer patients in
      the variable-duration group receiving the 12-week regimen had adverse events and
      withdrew than in the group receiving the 24-week regimen (P=0.045). The rate of
      relapse (defined as HCV not detectable at the end of treatment but detectable at
      the end of follow-up) was 3.6 percent in the standard-duration group and 8.9
      percent in the variable-duration group (P=0.16). Overall, the rate of sustained
      virologic response was 80 percent among patients with HCV genotype 2 and 66
      percent among those with genotype 3 (P<0.001). CONCLUSIONS: A shorter course of
      therapy over 12 weeks with peginterferon alfa-2b and ribavirin is as effective as
      a 24-week course for patients with HCV genotype 2 or 3 who have a response to
      treatment at 4 weeks.

PMID- 15972870
TI  - Case records of the Massachusetts General Hospital. Case 19-2005. A 17-year-old
      girl with respiratory distress and hemiparesis after surviving a tsunami.

PMID- 15972871
TI  - Sudden death after myocardial infarction--who needs prophylaxis, and when?

PMID- 15972872
TI  - Adjuvant chemotherapy for non-small-cell lung cancer--the smoke clears.

PMID- 15972873
TI  - Type 1 diabetes--does suppressing T cells increase insulin?

PMID- 15972874
TI  - How Ebola virus infects cells.

PMID- 15972875
TI  - Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial
      infarction.

PMID- 15972876
TI  - Cardiovascular risk associated with celecoxib.

PMID- 15972877
TI  - Morphine, gabapentin, or their combination for neuropathic pain.

PMID- 15972878
TI  - Blast injuries.

PMID- 15972879
TI  - Boxed warning added to promethazine labeling for pediatric use.

PMID- 15972880
TI  - Treatment of survivors after the tsunami.

PMID- 15972881
TI  - The effects of blocking the actions of estrogen and progesterone on the rates of
      proliferation and apoptosis of cervical epithelial and stromal cells during the
      second half of pregnancy in rats.
AB  - Serum levels of the ovarian hormones relaxin, estrogen, and progesterone are
      elevated during the second half of 23-day rat pregnancy when dramatic growth of
      the cervix occurs. Recently, we demonstrated that relaxin contributes to cervical
      growth by both promoting cell proliferation and inhibiting apoptosis of cervical
      cells during late pregnancy. The objective of this study was to determine the
      influence of estrogen and progesterone on the rates of proliferation and
      apoptosis of cervical cells at 3-day intervals during the second half of rat
      pregnancy. The actions of estrogen and progesterone were blocked with s.c.
      injections of estrogen antagonist ICI 182,780 and progesterone antagonist RU486,
      respectively. To evaluate cell proliferation, 5'-bromo-2'-deoxyuridine was
      injected s.c. 8 h before cervixes were collected. Terminal deoxynucleotidyl
      transferase-mediated deoxyuridine 5'-triphosphate nick end-labeling was used to
      detect apoptotic cells. Proliferating and apoptotic cells were identified by
      immunohistochemistry, and the rates at which these processes occurred were
      determined by morphometric analysis. Blocking the actions of estrogen and
      progesterone decreased the rates of proliferation and increased the rates of
      apoptosis of both cervical epithelial and stromal cells during late pregnancy.
      However, blocking the actions of progesterone had the opposite effects on
      apoptosis of both cervical epithelial and stromal cells during the middle of
      pregnancy. In conclusion, this study provides evidence that estrogen and
      progesterone, like relaxin, contribute to the increase in the cervical cell
      content during late pregnancy by promoting proliferation and inhibiting apoptosis
      of cervical cells.

PMID- 15972882
TI  - Estrogen disruption of neonatal ovine uterine development: effects on gene
      expression assessed by suppression subtraction hybridization.
AB  - Inappropriate exposure of neonatal sheep to estrogen during critical
      developmental periods inhibits or retards endometrial gland morphogenesis and
      reduces uterine growth. Studies were conducted to identify mechanisms mediating
      estrogen disruption of neonatal ovine uterine development by analysis of
      candidate growth factor systems and using suppression subtraction hybridization
      (SSH). In study 1, sheep were exposed either to corn oil as a control or to
      estradiol valerate (EV) from birth to Postnatal Day (PND) 14, which ablated
      endometrial gland development. Estradiol valerate decreased uterine FGF7
      (fibroblast growth factor 7) and MET (hepatocyte growth factor receptor)
      expression and increased INHBA (inhibin betaA). The SSH identified a number of
      genes responsive to EV, which included GSTM3 (glutathione S-transferase), IDH1
      (cytosolic NADP-isocitrate dehydrogenase), PECI (peroxisomal D(3),D(2)-enoyl
      coenzyme A isomerase), OAS1 (2',5'-oligoadenylate 40/46-kDa synthetase), IGFBP3
      (insulin-like growth factor-binding protein-3), TEGT (testis-enhanced gene
      transcript), CXCL10 (interferon-gamma-inducible protein 10), and IGLV
      (immunoglobulin V). These mRNAs were expressed predominantly in the endometrial
      epithelia (GSTM3, IDH1, PEC1, OAS1, and TEGT), stroma (IGFBP3), or immune cells
      (CXCL10 and IGLV). In study 2, effects of estrogen exposure on uterine gene
      expression were determined during three different critical developmental periods
      (PNDs 0-14, 14- 28, and 42-56). Estrogen exposure decreased expression of the SSH
      identified genes, particularly those from PNDs 0-14. These studies suggest that
      estrogen disruption of postnatal uterine development involves period-specific
      effects on expression of genes predominantly in the endometrial epithelium. The
      SSH-identified, estrogen-disrupted genes represent new candidate regulators of
      postnatal endometrial adenogenesis.

PMID- 15972883
TI  - Inhibition of luteinizing hormone secretion by localized administration of
      estrogen, but not dihydrotestosterone, is enhanced in the ventromedial
      hypothalamus during feed restriction in the young wether.
AB  - The ability of steroids to inhibit LH secretion is enhanced during
      undernutrition. To identify potential hypothalamic sites at which this
      enhancement may occur, we examined LH secretion in feed-restricted or fed young
      wethers treated with locally administered metabolites of testosterone. In
      experiment 1, microimplants containing crystalline estradiol-17beta (E) or
      cholesterol were administered via chronic guide tubes directed to the preoptic
      area (POA) or ventromedial hypothalamus (VMH) in fed or feed-restricted wethers.
      E treatment in the VMH decreased LH pulse frequency, pulse amplitude, and mean LH
      concentration in feed-restricted, but not fed, wethers. E may act in the POA to
      suppress LH under feed restriction, but definite conclusions cannot be drawn
      because of steroid-independent effects of feed restriction on LH pulse frequency.
      In experiment 2, the effect of dihydrotestosterone (DHT) in the VMH was
      determined. DHT administration to the VMH did not alter LH secretion in either
      feed-restricted or fed wethers. Thus the VMH is one site wherein E negative
      feedback is enhanced during feed restriction in the wether. In contrast, we found
      no evidence for enhanced responsiveness to androgen negative feedback within the
      VMH of feed-restricted wethers. We suggest that increased sensitivity within the
      VMH to E, but not to DHT, is important for suppressing LH secretion in
      undernourished male sheep.

PMID- 15972884
TI  - Impact of nutrition on oocyte quality: cumulative effects of body composition and
      diet leading to hyperinsulinemia in cattle.
AB  - The present study sought to assess the combined effects of body composition and
      diet (level of feeding) on the postfertilization developmental potential of
      oocytes recovered from heifers using ultrasound-guided transvaginal follicular
      aspiration and to relate oocyte quality to the metabolic status of these animals.
      By collecting oocytes on repeated occasions spanning several weeks, it was
      possible to assess the cumulative effects of changes in nutritional status on
      oocyte quality over this period. Twenty-four heifers of low and moderate body
      condition were placed on one of two levels of feeding (equivalent to once or
      twice the maintenance requirements of these animals). Oocytes were recovered at
      two defined time points within each of three successive estrous cycles and were
      matured, fertilized, and cultured to the blastocyst stage in vitro. The results
      show that the effect of feeding level on oocyte quality is dependent on the body
      condition of the animal, with the high level of feeding being beneficial to
      oocytes from animals of low body condition but detrimental to oocytes from
      animals of moderately high body condition. Furthermore, the effects of high
      levels of feeding on oocyte quality were cumulative, with blastocyst yields for
      relatively fat heifers on twice the maintenance requirement deteriorating with
      time relative to yields for relatively thin heifers on the same level of feeding.
      Finally, a significant proportion of the moderately fat animals on the high level
      of feeding were hyperinsulinemic, and we show, to our knowledge for the first
      time in ruminants, that this condition is associated with impaired oocyte
      quality.

PMID- 15972885
TI  - Expression and localization of alpha-smooth muscle and gamma-actins in the
      pregnant rat myometrium.
AB  - The myometrium undergoes dramatic changes as pregnancy progresses through phases
      of proliferation, hypertrophy, contractile state and labor. In this study, we
      showed that the composition of the muscle actin isoforms, a major component of
      the myometrial contractile apparatus and cytoskeleton, was modified during
      pregnancy. The expression of smooth muscle alpha-actin (Acta2, which we
      abbreviate as alpha-SM-actin) and gamma-actin mRNAs and proteins was examined by
      real-time polymerase chain reaction and Western immunoblot, and was localized
      with immunohistochemistry, in the nonpregnant, pregnant, and postpartum rat
      uterus. Both alpha-SM-actin (vascular specific actin isoform) and gamma-actin
      (predominant in visceral smooth muscle) were detected in the rat myometrium.
      Myometrial expression of alpha-SM-actin mRNA and protein was high throughout
      pregnancy. The transcript and protein levels of gamma-actin were increased
      significantly in the second part of gestation (31.8-fold increase for mRNA and
      16.7-fold increase for protein relative to nonpregnant). The localization of
      gamma-actin was markedly altered during pregnancy. In early gestation, myometria
      from empty and gravid uterine horns of the unilaterally pregnant rats showed
      abundant gamma-actin immunostaining in the longitudinal layer but weak staining
      in the circular layer. Gamma-actin immunostaining increased in only the circular
      layer of the gravid horn after midgestation and remained low in the empty one.
      Gamma-actin protein translocated to the membranous region of uterine myocytes at
      late gestation. The temporal alteration in gamma-actin expression and
      localization at late gestation suggested that this change in myometrial
      composition of contractile proteins is important to adequately prepare the
      myometrium for the development of optimal contractions during labor.

PMID- 15972886
TI  - Immunolocalization and regulation of cystatin 12 in mouse testis and epididymis.
AB  - In previous studies, we identified a new member of the male reproductive tract
      subgroup within family 2 cystatins, termed cystatin 12 (Cst12, previously known
      as Cst TE-1 or Cres3). The mouse Cst12 mRNA was primarily localized to the
      Sertoli cells in the testis and to the epithelial cells of the proximal caput
      region of the epididymis. In this report, studies were carried out to
      characterize the cystatin 12 (CST12) protein in mouse testis and epididymis. A
      recombinant His-CST12 fusion protein was expressed in E. coli and purified to
      generate an anti-CST12 polyclonal antibody. Western blot analysis showed little
      or no cross-reaction between the anti-CST12 antibody and several other known male
      reproductive tract cystatins. Immunohistochemistry revealed that CST12 protein
      was predominantly localized to the cytoplasm of Sertoli cells in the seminiferous
      epithelium in a stage-dependent manner. All stages showed high levels of
      expression except stages VII and VIII, in which very limited expression of CST12
      was observed. In the epididymis, CST12 was highly expressed in the cytoplasm of
      the epithelial cells in the proximal caput and secreted into the lumen. The mouse
      CST12 protein was also detected in other regions of the epididymis; however, the
      localization varied greatly along the epididymal tubules. Indirect
      immunofluorescence showed that CST12 protein was localized to the cytoplasmic
      droplets in both testicular and epididymal spermatozoa. These observations
      suggest that CST12 protein may play a specialized role during spermatogenesis and
      sperm maturation. Northern blot analyses demonstrated that Cst12 transcript
      levels in the epididymis decreased after castration, and testosterone propionate
      (T) treatment further repressed the expression of this gene. However, 17-beta
      estradiol (E) administration maintained the expression of Cst12 mRNA after
      castration, whereas treatment with both T and E failed to maintain Cst12 mRNA
      levels in epididymis. These results suggest that androgen and estrogen, probably
      with other testicular factors, are involved in the regulation of this gene.

PMID- 15972888
TI  - Extreme regression.
AB  - We develop a new method for describing patient characteristics associated with
      extreme good or poor outcome. We address the problem with a regression model
      composed of extrema (maximum and minimum) functions of the predictor variables.
      This class of models allows for simple regression function inversion and results
      in level sets of the regression function which can be expressed as interpretable
      Boolean combinations of decisions based on individual predictors. We develop an
      estimation algorithm and present clinical applications to symptoms data for
      patients with Hodgkin's disease and survival data for patients with multiple
      myeloma.

PMID- 15972887
TI  - Androgens augment the mitogenic effects of oocyte-secreted factors and growth
      differentiation factor 9 on porcine granulosa cells.
AB  - In this study, we test the hypothesis that the growth-promoting action of
      androgens on granulosa cells requires paracrine signaling from the oocyte. Mural
      granulosa cells (MGCs) from small antral (1-3 mm) prepubertal pig follicles were
      cultured in the presence or absence of denuded oocytes (DO) from the same
      follicles to determine whether mitogenic and/or steroidogenic responses, to
      combinations of FSH, insulin-like growth factor 1 (IGF1), and dihydrotestosterone
      (DHT) were influenced by oocyte-secreted factors (OSFs). To further explore the
      identity of such factors we performed the same experiments, substituting growth
      differentiation factor 9 (GDF9), a known OSF, for the DO. OSFs and GDF9 both
      potently enhanced IGF1-stimulated proliferation, and inhibited FSH-stimulated
      progesterone secretion. Alone, DHT had little effect on DNA synthesis, but
      significantly enhanced the mitogenic effects of OSFs or GDF9 in the presence of
      IGF1. Denuded oocytes, GDF9, and DHT independently inhibited FSH-stimulated
      progesterone secretion, and androgen, together with DO or GDF9, caused the most
      potent steroidogenic inhibition. Focusing on mitogenic effects, we demonstrate
      that both natural androgen receptor (AR) agonists, testosterone and DHT, dose
      dependently augmented the mitogenic activity of DO or GDF9. Antiandrogen
      (hydroxyflutamide) treatment, which is used to block androgen receptor activity,
      opposed the interaction between androgen and GDF9. In conclusion, androgens
      stimulate porcine MGC proliferation in vitro by potentiating the growth-promoting
      effects of oocytes or GDF9, via a mechanism that involves the AR. These signaling
      pathways are likely to be important regulators of folliculogenesis in vivo, and
      may contribute to the excess follicle growth that is observed in androgen-treated
      female animals.

PMID- 15972889
TI  - A simple meta-analytic approach for using a binary surrogate endpoint to predict
      the effect of intervention on true endpoint.
AB  - A surrogate endpoint is an endpoint that is obtained sooner, at lower cost, or
      less invasively than the true endpoint for a health outcome and is used to make
      conclusions about the effect of intervention on the true endpoint. In this
      approach, each previous trial with surrogate and true endpoints contributes an
      estimated predicted effect of intervention on true endpoint in the trial of
      interest based on the surrogate endpoint in the trial of interest. These
      predicted quantities are combined in a simple random-effects meta-analysis to
      estimate the predicted effect of intervention on true endpoint in the trial of
      interest. Validation involves comparing the average prediction error of the
      aforementioned approach with (i) the average prediction error of a standard meta
      analysis using only true endpoints in the other trials and (ii) the average
      clinically meaningful difference in true endpoints implicit in the trials.
      Validation is illustrated using data from multiple randomized trials of patients
      with advanced colorectal cancer in which the surrogate endpoint was tumor
      response and the true endpoint was median survival time.

PMID- 15972890
TI  - Effects of the sugar headgroup of a glycoglycerolipid on the phase behavior of
      phospholipid model membranes in the dry state.
AB  - Glycolipids are important components of almost all biological membranes. They
      possess unique properties that have only been incompletely characterized so far.
      The plant glycolipid digalactosyldiacylglycerol (DGDG) strongly influences the
      physical behavior of phospholipid model membranes in both the dry and hydrated
      state. It was, however, unclear whether the strong effect of DGDG on the gel to
      liquid-crystalline phase transition temperature (Tm) in dry phosphatidylcholine
      (PC) bilayers is mainly due to the high degree of unsaturation of the DGDG fatty
      acyl chains or to interactions between the DGDG and PC headgroups. Also, no
      information on the relative effectiveness of membrane bound and free sugars on
      membrane phase behavior was available. We have used Fourier-transform infrared
      spectroscopy (FTIR) to investigate the phase properties and H-bonding patterns in
      dry membranes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine
      (POPC) containing one saturated and one monounsaturated (16:0/18:1) fatty acid
      and different fractions of DGDG or 1,2-dilinolenoyl-sn-glycero-3
      phosphatidylcholine (DLPC) (18:3/18:3). This was compared to the effects of
      galactose (Gal) and digalactose (diGal). All additives depressed Tm of the dry
      membranes, but DGDG was much more effective than DLPC or Gal. diGal had a similar
      effect as DGDG, pointing to the sugar headgroup as the component with the
      strongest influence on membrane phase behavior. A combination of DLPC and diGal,
      which should theoretically be equivalent to DGDG, was much more effective than
      the galactolipid. H-bonding interactions with the P = O group of PC were also
      stronger for free diGal than for DGDG, indicating that the free sugar may be
      structurally more flexible to adopt an optimal conformation for interactions with
      the PC headgroup.

PMID- 15972891
TI  - Transmembrane and secreted MUC1 probes show trafficking-dependent changes in O
      glycan core profiles.
AB  - The human mucin MUC1 is expressed both as a transmembrane heterodimeric protein
      complex that recycles via the trans-Golgi network (TGN) and as a secreted
      isoform. To determine whether differences in cellular trafficking might influence
      the O-glycosylation profiles on these isoforms, we developed a model system
      consisting of membrane-bound and secretory-recombinant glycosylation probes.
      Secretory MUC1-S contains only a truncated repeat domain, whereas in MUC1-M
      constructs this domain is attached to the native transmembrane and cytoplasmic
      domains of MUC1 either directly (M0) or via an intermitting nonfunctional (M1) or
      functional sperm protein-enterokinase-agrin (SEA) module (M2); the SEA module
      contains a putative proteolytic cleavage site and is associated with proteins
      receiving extensive O-glycosylation. We showed that MUC1-M2 simulates endogenous
      MUC1 by recycling from the cell surface of Chinese hamster ovary (CHO) mutant
      ldlD14 cells through intracellular compartments where its glycosylation
      continues. The profiles of O-linked glycans on MUC1-S secreted by epithelial EBNA
      293 and MCF-7 breast cancer cells revealed patterns dominated by core 2-based
      oligosaccharides. In contrast, the respective membrane-shed probes expressed in
      the same cells showed a complete shift to patterns dominated by sialyl core 1. In
      conclusion, glycan core profiles reflected the subcellular trafficking pathways
      of the secretory or membranous probes and the modifying activities of the
      resident glycosyltransferases.

PMID- 15972892
TI  - Identification of residues essential for carbohydrate recognition and cation
      dependence of the 46-kDa mannose 6-phosphate receptor.
AB  - The 46 kDa cation-dependent mannose 6-phosphate receptor (CD-MPR) plays an
      essential role in the biogenesis of lysosomes by diverting newly synthesized
      mannose 6-phosphate (Man-6-P)-containing lysosomal enzymes from the secretory
      pathway to acidified endosomes. Previous crystallographic studies of the CD-MPR
      have identified 11 amino acids within its carbohydrate binding pocket. These
      residues were evaluated quantitatively by assaying the binding affinity of mutant
      receptors containing a single amino acid substitution toward a lysosomal enzyme.
      The results show that substitution of Gln-66, Arg-111, Glu-133, or Tyr-143
      results in a >800-fold decrease in affinity, demonstrating these four amino acids
      are essential for carbohydrate recognition by the CD-MPR. Solution binding and
      surface plasmon resonance analyses demonstrated that the presence of Mn2+
      enhanced the affinity of the CD-MPR for a lysosomal enzyme by 2- to 4-fold and
      increased the stoichiometry of the interaction between a heterogeneous population
      of a lysosomal enzyme and the receptor by approximately 3-fold. In contrast,
      substitution of Asp-103 results in a protein that no longer exhibits enhanced
      binding affinities or altered stoichiometry in the presence of cations, and
      electron spin resonance demonstrated that the D103S mutant exhibits a 6-fold
      lower affinity for Mn2+ than the wild-type receptor (Kd = 3.7 6 1.4 mM versus 0.6
      6 0.1 mM). Chemical cross-linking revealed that Mn2+ influences the stoichiometry
      of interaction between the CD-MPR and lysosomal enzymes by increasing the
      oligomeric state of the receptor from dimer to higher order oligomers. Taken
      together, these studies provide the molecular basis for high affinity
      carbohydrate recognition by the CD-MPR. Furthermore, Asp-103 has been identified
      as the key residue which mediates the effects of divalent cations on the binding
      properties of the CD-MPR.

PMID- 15972893
TI  - Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are
      selectively expressed on eosinophils and recognize 6'-sulfo-sialyl Lewis X as a
      preferred glycan ligand.
AB  - Mouse sialic acid-binding immunoglobulin-like lectin F (Siglec-F) is an
      eosinophil surface receptor, which contains an immunoreceptor tyrosine-based
      inhibitory motif (ITIM) in its cytoplasmic domain, implicating it as a regulator
      of cell signaling as documented for other siglecs. Here, we show that the
      sialoside sequence 6'-sulfo-sLe(X) (Neu5Acalpha2-3[6-SO4] Galbeta1-4[Fucalpha1
      3]GlcNAc) is a preferred ligand for Siglec-F. In glycan array analysis of 172
      glycans, recombinant Siglec-F-Fc chimeras bound with the highest avidity to 6'
      sulfo-sLe X. Secondary analysis showed that related structures, sialyl-Lewis X
      (sLe X) and 6-sulfo-sLe X containing 6-GlcNAc-SO4 showed much lower binding
      avidity, indicating significant contribution of 6-Gal-SO4 on Siglec-F binding to
      6'-sulfo-sLe x. The lectin activity of Siglec-F on mouse eosinophils was "masked"
      by endogenous cis ligands and could be unmasked by treatment with sialidase.
      Unmasked Siglec-F mediated mouse eosinophil binding and adhesion to multivalent
      6'-sulfo-sLe X structure, and these interactions were inhibited by anti-Siglec-F
      monoclonal antibody (mAb). Although there is no clear-cut human ortholog of
      Siglec-F, Siglec-8 is encoded by a paralogous gene that is expressed selectively
      by human eosinophils and has recently been found to recognize 6'-sulfo-sLe X.
      These observations suggest that mouse Siglec-F and human Siglec-8 have undergone
      functional convergence during evolution and implicate a role for the interaction
      of these siglecs with their preferred 6'-sulfo-sLe X ligand in eosinophil
      biology.

PMID- 15972894
TI  - Chromatographic resolution of glucosidic compounds, ginsenosides on
      polyethersulphone membrane, and its application to the quantitative immunoassay
      for ginseng saponins.
AB  - A method has been devised for the chromatographic resolution of glucosidic
      compounds, ginseng saponins, on polyethersulphone (PES) membrane. The method
      results in good resolution and quantitative immunoassay for ginsenoside Rb1 (G
      Rb1), G-Rc, and G-Rd in crude extracts of various ginsengs. The newly established
      method is simpler and applies for quantitative analysis. Ginsenosides developed
      by acetonitrile-water-acetic acid solvent system on a PES membrane were directly
      treated with a NaIO4 solution followed by bovine serum albumin (BSA), resulting
      in a ginsenoside-BSA conjugate on a PES membrane. Anti-G-Rb1 monoclonal antibody
      (MAb) was bound, and then a second antibody labeled with peroxidase directed
      against the first antibody. Finally a substrate reacted to the enzyme and gave
      staining. The stained membrane was scanned, and spots were analyzed
      quantitatively using NIH Image software. At least 62.5 ng of G-Rb1, G-Rc, and G
      Rd were clearly detectable individually. Three ginsenosides can be analyzed
      quantitatively between 0.125 and 2.0 microg.

PMID- 15972896
TI  - Different kinds of time.

PMID- 15972895
TI  - Dynamic changes in protein-protein interaction and protein phosphorylation probed
      with amine-reactive isotope tag.
AB  - We present an approach for quantitative analysis of changes in the composition
      and phosphorylation of protein complexes by MS. It is based on a new class of
      stable isotope-labeling reagent, the amine-reactive isotope tag (N-isotag), for
      specific and quantitative labeling of peptides following proteolytic digestion of
      proteins. Application of the N-isotag method to the analysis of Rad53, a DNA
      damage checkpoint kinase in Saccharomyces cerevisiae, led to the identification
      of dynamic associations between Rad53 and the nuclear transport machinery,
      histones, and chromatin assembly proteins in response to DNA damage. Over 30
      phosphorylation sites of Rad53 and its associated proteins were identified and
      quantified, and they showed different changes in phosphorylation in response to
      DNA damage. Interestingly, Ser789 of Rad53 was found to be a major initial
      phosphorylation site, and its phosphorylation regulates the Rad53 abundance in
      response to DNA damage. Collectively, these results demonstrate that N-isotag
      based quantitative MS is generally applicable to study dynamic changes in the
      composition of protein complexes and their phosphorylation patterns in a site
      specific manner in response to different cell stimuli.

PMID- 15972897
TI  - Combined training of GPs and practice-assistants on peripheral arterial disease:
      positive effects after six months.
AB  - OBJECTIVES: To improve the use of the ankle-brachial index (ABI) measurement, and
      management of patients with peripheral arterial disease (PAD) a combined
      training, targeting GPs and practice assistants (PAs) was developed. To measure
      the effect of the combined training on the management of patients with PAD, a
      cross-sectional study was performed. METHODS: Fifty consecutive patients referred
      by GPs to a vascular surgery out-patient clinic were analysed. Six months after
      the training an additional fifty patients were included. In all patients the ABI
      measurement, risk factor management, and treatment as performed by the GP, prior
      to referral, were analysed. RESULTS: The measurement of the ABI significantly
      increased from 10% before the training to 53% after the training (GPs with
      training: 83%, GPs without training: 35%; P: 0.001). The referral of patients
      with actual PAD significantly increased from 32% before the training to 70% after
      the training (GPs with training: 83%, GPs without training: 59%; P: 0.05). The
      presence and treatment of risk factors did not differ between the groups.
      CONCLUSIONS: Within the limitations of a before and after study the combined
      training of GPs and PAs appears to be an effective method to increase ABI
      measurements and significantly improve adequate diagnostics.

PMID- 15972898
TI  - The biology of integration of the anterior cruciate ligament.

PMID- 15972899
TI  - The use of percutaneous autologous bone marrow transplantation in nonunion and
      avascular necrosis of bone.

PMID- 15972900
TI  - Learning the vagaries of computer-assisted total knee replacement.

PMID- 15972901
TI  - Triple osteotomy of the pelvis for acetabular dysplasia: results at a mean follow
      up of 15 years.
AB  - We report the long-term results of 51 pelvic osteotomies in 43 patients with a
      mean follow-up of 15 years (13 to 20). The mean age of the patients was 28 years
      (14 to 46). At review three patients were lost to follow-up, and six had received
      a total hip arthroplasty. Of 48 hips, 42 (88%) were preserved, with good to
      excellent clinical results in 27 (64%). Pre-operatively, 41 (80%) of the treated
      hips had shown no sign of osteoarthritis. Thirty-one (65%) hips showed no
      progression of osteoarthritis after follow-up for 15 years. Significant negative
      factors for good long-term results were the presence of osteoarthritic changes
      and a fair or poor clinical score pre-operatively. Pelvic reorientation osteotomy
      for symptomatic hip dysplasia can give satisfactory and reproducible long-term
      clinical results.

PMID- 15972902
TI  - Medium-term results of the Charnley low-offset femoral stem.
AB  - A reduced femoral offset in total hip replacement has been thought to be
      disadvantageous. We reviewed the results of 54 consecutive primary total hip
      replacements in 49 patients (mean age of 68 years) performed between August 1990
      and December 1994, with a mean follow-up of 8.8 years (sd 2.1). The mean pre
      operative femoral offset for these hips was 41 mm (sd 7.4). All patients received
      a low-offset Charnley stem and a polyethylene cup inserted by a single surgeon.
      At their latest follow-up, surviving patients had a significant improvement in
      the performance of their hip. Three had undergone revision, one each for deep
      infection, recurrent dislocation and late pain with subluxation. No hips had been
      revised, or were at risk of revision, for aseptic loosening. The mean annual
      linear rate of wear was 0.2 mm (sd 0.08) for the whole group. There was no
      correlation between the pre-operative femoral offset and the post-operative rate
      of wear. Our survivorship estimate was 91% when revision for any reason was taken
      as an end-point, but 100% if aseptic loosening was considered as the end-point.
      Our study demonstrates that a low-offset femoral stem can produce good, medium
      term results.

PMID- 15972903
TI  - Influence of stem geometry on the stability of polished tapered cemented femoral
      stems.
AB  - Polished, tapered stems are now widely used for cemented total hip replacement
      and many such designs have been introduced. However, a change in stem geometry
      may have a profound influence on stability. Stems with a wide, rectangular
      proximal section may be more stable than those which are narrower proximally. We
      examined the influence of proximal geometry on stability by comparing the two
      year migration of the Exeter stem with a more recent design, the CPS-Plus, which
      has a wider shoulder and a more rectangular cross-section. The hypothesis was
      that these design features would increase rotational stability. Both stems
      subsided approximately 1 mm relative to the femur during the first two years
      after implantation. The Exeter stem was found to rotate into valgus (mean 0.2
      degrees , sd 0.42 degrees ) and internally rotate (mean 1.28 degrees , sd 0.99
      degrees ). The CPS-Plus showed no significant valgus rotation (mean 0.07
      [correction] degrees, sd 0.29 [correction] degrees ) or internal rotation (mean 
      0.03 degrees , sd 0.75 degrees ). A wider, more rectangular cross-section
      improves rotational stability and may have a better long-term outcome.

PMID- 15972904
TI  - Ten-year survival of the MS-30 matt-surfaced cemented stem.
AB  - The Morscher-Spotorno (MS-30) femoral stem is a stainless-steel, straight, three
      dimensionally tapered, collarless implant for cemented fixation in total hip
      replacement. We report the results at ten years of a consecutive series of 124
      total hip replacements in 121 patients with the matt-surfaced MS-30 stem and an
      alumina ceramic head of 28-mm diameter. All the stems were fixed with Palacos
      bone cement with gentamicin using a modern cementing technique. They were
      combined with an uncemented, press-fit cup. The mean period of observation was
      10.2 years (8.3 to 12.1) and no patient was lost to follow-up. Twenty-seven
      patients (22%) died with the implant in situ. Nine could only be interviewed by
      telephone. We included 85 patients with 88 hips in the clinical and radiological
      follow-up examinations. None of the stems or cups had been revised. The Harris
      hip score was excellent or good in 97% (85 hips) and moderate in 3% (three hips).
      Radiologically, six hips (6.8%) had osteolysis adjacent to the stem, mostly in
      Gruen zone 7. Twenty (22.7%) showed one or more radiolucent lines. Twenty-two
      stems (25%) had subsided by 2 mm to 5 mm. In these cases two showed osteolysis
      (9.1%) with subsidence and four without (6.1%). Radiolucent lines were seen in
      seven with migration (31.8%) and in 13 without (19.7%). No infections and no
      acetabular osteolysis were observed. The clinical results were excellent with
      survivorship after ten years of 100% and only a slightly statistically non
      significant higher rate of osteolysis and radiolucency in cases of subsidence.

PMID- 15972905
TI  - Natural history of fixed flexion deformity following total knee replacement: a
      prospective five-year study.
AB  - We investigated fixed flexion deformity (FFD) after total knee replacement (TKR).
      Data relating to 369 cruciate-retaining unilateral TKRs performed at a single
      institution were collected prospectively. Fixed flexion was measured pre
      operatively and at one week, six months, 18 months, three years and five years
      after surgery. Using binary logistic regression, pre-operative FFD was a
      predictor of post-operative FFD > 10 degrees at one week (p = 0.006) and six
      months (p = 0.003) following surgery. Gender was a predictor at one week (p =
      0.0073) with 24% of women showing a FFD > 10 degrees compared with 37% of men. We
      have shown that a gradual improvement in knee extension can be expected up to
      three years after surgery in knees with FFD. By this time residual FFD is mild or
      absent in the majority of patients, including those who had a severe pre
      operative FFD.

PMID- 15972906
TI  - A comparison of knee braces during walking for the treatment of osteoarthritis of
      the medial compartment of the knee.
AB  - In this cross-over study, we evaluated two types of knee brace commonly used in
      the conservative treatment of osteoarthritis of the medial compartment. Twelve
      patients confirmed radiologically as having unilateral osteoarthritis of the
      medial compartment (Larsen grade 2 to grade 4) were studied. Treatment with a
      simple hinged brace was compared with that using a valgus corrective brace. Knee
      kinematics, ground reaction forces, pain and function were assessed during
      walking and the Hospital for Special Surgery scores were also determined.
      Significant improvements in pain, function, and loading and propulsive forces
      were seen with the valgus brace. Treatment with a simple brace showed only
      significant improvements in loading forces. Our findings suggest that although
      both braces improved confidence and function during gait, the valgus brace showed
      greater benefit.

PMID- 15972907
TI  - Influence of surface geometry and the cam-post mechanism on the kinematics of
      total knee replacement.
AB  - Abnormal sagittal kinematics after total knee replacement (TKR) can adversely
      affect functional outcome. Two important determinants of knee kinematics are
      component geometry and the presence or absence of a posterior-stabilising
      mechanism (cam-post). We investigated the influence of these variables by
      comparing the kinematics of a TKR with a polyradial femur with a single radius
      design, both with and without a cam-post mechanism. We assessed 55 patients,
      subdivided into four groups, who had undergone a TKR one year earlier by using an
      established fluoroscopy protocol in order to examine their kinematics in vivo.
      The kinematic profile was obtained by measuring the patellar tendon angle through
      the functional knee flexion range (0 degrees to 90 degrees ) and the results
      compared with 14 normal knees. All designs of TKR had abnormal sagittal
      kinematics compared with the normal knee. There was a significant (p < 0.05)
      difference between those of the two TKRs near to full extension. The presence of
      the cam-post mechanism did not influence the kinematics for either TKR design.
      These differences suggest that surface geometry is a stronger determinant of
      kinematics than the presence or absence of a cam-post mechanism for these two
      designs. This may be because the cam-post mechanism is ineffective.

PMID- 15972908
TI  - Survivorship of the Souter-Strathclyde elbow replacement in the young
      inflammatory arthritis elbow.
AB  - We divided 309 patients with an inflammatory arthritis who had undergone primary
      elbow replacement using the Souter-Strathclyde implant into two groups according
      to their age. The mean follow-up in the older group (mean age 64 years) was 7.3
      years while in the younger patients (mean age 42 years) it was 12 years.
      Survivorship for three different failure end-points (revision, revision because
      of aseptic loosening of the humeral component, and gross loosening of the humeral
      implant), was compared in both groups. Our findings showed that there was no
      significant difference in the incidence of loosening when young rheumatoid
      patients were compared with an older age group.

PMID- 15972909
TI  - Souter-Strathclyde total elbow arthroplasty in rheumatoid arthritis: medium-term
      results.
AB  - We present the outcome of 47 Souter-Strathclyde replacements of the elbow with a
      mean follow-up of 82 months (12 to 129). The clinical results were assessed using
      a condition-specific outcome measure. The mean total score (maximum 100) before
      the operation was 47.21 and improved to 79.92 (p < 0.001). The mean pain score
      (maximum 50) improved from 21.41 to 46.70 (p < 0.001) and the mean functional
      component of the score (maximum 30) from 11.19 to 18.65 (p < 0.001). There was
      negligible change in the score for the range of movement although a significant
      improvement in mean flexion from 124 degrees to 136 degrees was noted (p <
      0.001). Revision surgery was required in four patients, for dislocation, wound
      dehiscence and early infection in one, late infection in two and aseptic
      loosening in one. The cumulative survival was 75% at nine years for all causes of
      failure and 97% at ten years for aseptic loosening alone. Our study demonstrates
      the value of the Souter-Strathclyde total elbow arthroplasty in providing relief
      from pain and functional improvement in rheumatoid patients.

PMID- 15972910
TI  - Results after 24 years of prophylactic surgery for rheumatoid atlantoaxial
      subluxation.
AB  - We evaluated the use of surgical stabilisation for atlantoaxial subluxation after
      a follow-up of 24 years in 50 rheumatoid patients who had some degree of pain but
      no major neurological deficit. The mortality of patients treated by atlantoaxial
      fusion was significantly lower than for those who received conservative
      treatment. The deaths resulted from infection or comorbid conditions. The
      significantly high relative risks of mortality from conservative treatment
      compared with surgical treatment were mutilating disease and susceptible factors
      on both of the HLA-DRB1 alleles. Relief from pain and neurological and functional
      recovery were better, and the radiological degree of atlantoaxial translocation
      was less in those who were surgically treated compared with those who were not.
      Two patients had superficial local infections after surgery. We conclude that
      prophylactic atlantoaxial fusion is better than conservative treatment in these
      patients.

PMID- 15972911
TI  - Health-related quality of life in patients before and after surgery for a
      herniated lumbar disc.
AB  - We investigated the pre-operative and one-year post-operative health-related
      quality of life (HRQOL) outcome by using a Euroqol (EQ-5D) questionnaire in 263
      patients who had undergone surgery for herniation of a lumbar disc. Data from the
      National Swedish Register for lumbar spinal surgery between 2001 and 2002 were
      used and, in addition, a comparison between our cohort and a Swedish EQ-5D
      population survey was performed. We analysed the pre- and post-operative quality
      of life data, age, gender, smoking habits, pain and walking capacity. The mean
      age of the patients was 42 years (20 to 66); 155 (59%) were men and 69 (26%)
      smoked. Pre-operatively, 72 (17%) could walk at least 1 km compared with 200
      (76%) postoperatively. The mean EQ-5D score improved from 0.29 to 0.70, and the
      HRQOL improved in 195 (74%) of the patients. The pre-operative score did not
      influence the post-operative score. In most patients, all five EQ-5D dimensions
      improved, but did not reach the level reported by an age- and gender-matched
      population sample (mean difference 0.17). Predictors for poor outcome were
      smoking, a short pre-operative walking distance, and a long history of back pain.

PMID- 15972913
TI  - Acetabular fractures: a 16-year prospective epidemiological study.
AB  - We prospectively analysed the epidemiology of acetabular fractures over a period
      of 16 years in order to identify changes in their incidence or other demographic
      features. Our study cohort comprised a consecutive series of 351 patients with
      acetabular fractures admitted to a single institution between January 1988 and
      December 2003. There was no significant change in the overall incidence of
      acetabular fractures, which remained at 3 patients/100 000/year. There was,
      however, a significant reduction in the number of men sustaining an acetabular
      fracture over the period (p < 0.02). The number of fractures resulting from falls
      from a height < 10 feet showed a significant increase (p < 0.002), but there was
      no change in those caused by motor-vehicle accidents. There was a significant
      reduction in the median Injury Severity score over the period which was
      associated with a significant decrease in mortality (p < 0.04) and a reduction in
      the length of hospital stay. The incidence of osteoarthritis noted during follow
      up of operatively-treated fractures declined from 31% to 14%, reflecting improved
      results with increasing subspecialisation. Our findings suggest that there will
      be a continuing need for some orthopaedic surgeons to specialise in the
      management of these fractures. In addition, the reductions in the Injury Severity
      score and mortality may be associated with improved road and vehicle safety.

PMID- 15972912
TI  - Deep-vein thrombosis in high-energy skeletal trauma despite thromboprophylaxis.
AB  - We report the incidence and location of deep-vein thrombosis in 312 patients who
      had sustained high-energy, skeletal trauma. They were investigated using magnetic
      resonance venography and Duplex ultrasound. Despite thromboprophylaxis, 36
      (11.5%) developed venous thromboembolic disease with an incidence of 10% in those
      with non-pelvic trauma and 12.2% in the group with pelvic trauma. Of patients who
      developed deep-vein thrombosis, 13 of 27 in the pelvic group (48%) and only one
      of nine in the non-pelvic group (11%) had a definite pelvic deep-vein thrombosis.
      When compared with magnetic resonance venography, ultrasound had a false-negative
      rate of 77% in diagnosing pelvic deep-vein thrombosis. Its value in the pelvis
      was limited, although it was more accurate than magnetic resonance venography in
      diagnosing clots in the lower limbs. Additional screening may be needed to detect
      pelvic deep-vein thrombosis in patients with pelvic or acetabular fractures.

PMID- 15972914
TI  - Chondroblastoma of bone: long-term results and functional outcome after
      intralesional curettage.
AB  - We undertook this retrospective study to determine the rate of recurrence and
      functional outcome after intralesional curettage for chondroblastoma of bone. The
      factors associated with aggressive behaviour of the tumour were also analysed. We
      reviewed 53 patients with histologically-proven chondroblastoma who were treated
      by intralesional curettage in our unit between 1974 and 2000. They were followed
      up for at least two years to a maximum of 27 years. Seven (13.2%) had a
      histologically-proven local recurrence. Three underwent a second intralesional
      curettage and had no further recurrence. Two had endoprosthetic replacement of
      the proximal humerus and two underwent below-knee amputation after aggressive
      local recurrence. One patient had the rare malignant metastatic chondroblastoma
      and eventually died. The mean Musculoskeletal Tumour Society functional score of
      the survivors was 94.2%. We conclude that meticulous intralesional curettage
      alone can achieve low rates of local recurrence and excellent long-term function.

PMID- 15972915
TI  - Regeneration of the proximal tibial epiphysis after infantile osteomyelitis:
      report of three cases with an eight- to 22-year follow-up.
AB  - We reviewed three infants with destructive osteomyelitis involving the proximal
      tibial epiphysis at a follow-up of eight to 22 years. All cases showed early
      radiographic destructive changes in the medial or lateral aspects of the
      epiphysis and metaphysis. Despite the ominous early appearance of the epiphysis,
      all cases showed spontaneous re-ossification of the epiphysis with restoration of
      the tibial condyle and preservation of joint congruity. The patients, however,
      developed a valgus or varus deformity which was treated satisfactorily with one
      to three proximal tibial osteotomies. The potential for regeneration of the
      epiphysis following infantile osteomyelitis of the proximal tibia suggests these
      cases should be treated expectantly with regard to joint congruity.

PMID- 15972916
TI  - Elective Caesarean section is associated with a reduction in developmental
      dysplasia of the hip in term breech infants.
AB  - We wished to establish whether delivery by Caesarean section influenced the
      incidence of developmental dysplasia of the hip in term breech infants compared
      with those delivered vaginally. We used maternal charts, singleton term breech
      presentation, mode of delivery and incidence of developmental dysplasia of the
      hip for births between January 1997 and October 2002. During the study period 46
      089 infants were born. We analysed a total of 941 breech infants of whom 756 were
      delivered by Caesarean section (515 pre-labour, 241 intrapartum) and 185
      vaginally. The incidence of developmental dysplasia of the hip according to the
      mode of delivery was 19 of 515 (3.69%) following pre-labour Caesarean section, 16
      of 241 (6.64%) for intrapartum Caesarean section and 15 of 185 (8.11%) after
      vaginal delivery. There was a lower incidence of developmental dysplasia of the
      hip among those infants delivered by elective Caesarean section compared with
      those delivered vaginally (p < 0.02). These results demonstrate a significantly
      lower incidence of developmental dysplasia of the hip in term singleton breech
      births delivered by elective, pre-labour Caesarean section and suggest that
      labour and delivery influence hip stability in predisposed infants.

PMID- 15972917
TI  - Osteotomy for congenital elevation of the scapula (Sprengel's deformity).
AB  - We report 12 consecutive cases of vertical scapular osteotomy to correct
      Sprengel's deformity, performed during a 16-year period, with a mean follow-up of
      10.4 years. The mean increase in abduction of the shoulder was 53 degrees . The
      cosmetic appearance improved by a mean of 1.5 levels on the Cavendish scale.
      Neither function nor cosmesis deteriorated with time. We recommend the procedure
      for correction of moderate deformities with a functional deficit.

PMID- 15972918
TI  - Prenatal ultrasound diagnosis of club foot: outcome and recommendations for
      counselling and follow-up.
AB  - Club foot was diagnosed by ultrasonography in 91 feet (52 fetuses) at a mean
      gestational age of 22.1 weeks (14 to 35.6). Outcome was obtained by chart review
      in 26 women or telephone interview in 26. Feet were classified as normal,
      positional deformity, isolated club foot or complex club foot. At initial
      diagnosis, 69 feet (40 fetuses) were classified as isolated club foot and 22 feet
      (12 fetuses) as complex club foot. The diagnosis was changed after follow-up
      ultrasound scan in 13 fetuses (25%), and the final ultrasound diagnosis was
      normal in one fetus, isolated club foot in 31 fetuses, and complex club foot in
      20 fetuses. At birth, club foot was found in 79 feet in 43 infants for a positive
      predictive value of 83%. Accuracy of the specific diagnosis of isolated club foot
      or complex club foot was lower; 63% at the initial ultrasound scan and 73% at the
      final scan. The difference in diagnostic accuracy between isolated and complex
      club foot was not statistically significant. In no case was postnatal complex
      club foot undiagnosed on fetal ultrasound and all inaccuracies were
      overdiagnoses. Karyotyping was performed in 25 cases. Abnormalities were noted in
      three fetuses, all with complex club foot and with additional findings on
      ultrasound.

PMID- 15972919
TI  - Immobilisation of forearm fractures in children: extended versus flexed elbow.
AB  - Redisplacement of unstable forearm fractures in plaster is common and may be the
      result of a number of factors. Little attention has been paid to the influence of
      immobilisation with the elbow extended versus flexed. We prospectively treated
      111 consecutive children from two centres with closed forearm fractures by closed
      reduction and casting with the elbow either extended (60) in China or flexed (51)
      in Israel. We compared the outcome of the two groups. There was no statistically
      significant difference in the distribution of the age of the patients, the site
      of fracture or the amount of angulation and displacement between the groups.
      During the first two weeks after reduction, redisplacement occurred in no child
      immobilised with the elbow extended and nine of 51 children (17.6%) immobilised
      with the elbow flexed. Immobilisation of unstable forearm fractures with the
      elbow extended appears to be a safe and effective method of maintaining
      reduction.

PMID- 15972920
TI  - A study of telephone screening and direct observation of surgical wound
      infections after discharge from hospital.
AB  - Post-discharge surveillance of surgical site infection is necessary if accurate
      rates of infection following surgery are to be available. We undertook a
      prospective study of 376 knee and hip replacements in 366 patients in order to
      estimate the rate of orthopaedic surgical site infection in the community. The
      inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We
      concluded that the use of telephone interviews of patients to identify the group
      at highest risk of having a surgical site infection (those who think they have an
      infection) with rapid follow-up by a professional trained to diagnose infection
      according to agreed criteria is an effective method of identifying infection
      after discharge from hospital.

PMID- 15972921
TI  - The management of leg-length discrepancy in Ollier's disease with a fully
      implantable lengthening nail.
AB  - Ollier's disease is characterised by severe deformity of the extremities and
      retarded growth because of multiple enchondromas. For correction of deformity,
      the Ilizarov method has been used although it has many complications. A 17-year
      old boy with Ollier's disease had a limb-length discrepancy of 17.4 cm, with a
      valgus deformity of the right knee and recurvatum of the femur of 23 degrees . He
      had undergone three unsuccessful attempts to correct the deformities by using
      external fixators. We used a fully implantable, motorised, lengthening and
      correction nail (Fitbone) to achieve full correction of all the deformities
      without complications. We decided to carry out the procedure in three stages.
      First, we lengthened the femur by 3.6 cm and the tibia by 4 cm. We then exchanged
      the femoral nail for a longer implant and achieved a further 6 cm of length. This
      reduced the shortening to 3.8 cm. When the boy has finished secondary school we
      will adjust the remaining discrepancy.

PMID- 15972922
TI  - Extracorporeal irradiated autogenous osteochondral graft: a histological study.
AB  - We examined osteochondral autografts, obtained at a mean of 19.5 months (3 to 48)
      following extracorporeal irradiation and re-implantation to replace bone defects
      after removal of tumours. The specimens were obtained from six patients (mean age
      13.3 years (10 to 18)) and consisted of articular cartilage (five), subchondral
      bone (five), external callus (one) and tendon (one). The tumour cells in the
      grafts were eradicated by a single radiation dose of 60 Gy. In three cartilage
      specimens, viable chondrocytes were detected. The survival of chondrocytes was
      confirmed with S-100 protein staining. Three specimens from the subchondral
      region and a tendon displayed features of regeneration. Callus was seen at the
      junction between host and irradiated bone.

PMID- 15972923
TI  - Hip morphology influences the pattern of damage to the acetabular cartilage:
      femoroacetabular impingement as a cause of early osteoarthritis of the hip.
AB  - Recently, femoroacetabular impingement has been recognised as a cause of early
      osteoarthritis. There are two mechanisms of impingement: 1) cam impingement
      caused by a non-spherical head and 2) pincer impingement caused by excessive
      acetabular cover. We hypothesised that both mechanisms result in different
      patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam
      and 16 an isolated pincer impingement. Cam impingement caused damage to the
      anterosuperior acetabular cartilage with separation between the labrum and
      cartilage. During flexion, the cartilage was sheared off the bone by the non
      spherical femoral head while the labrum remained untouched. In pincer
      impingement, the cartilage damage was located circumferentially and included only
      a narrow strip. During movement the labrum is crushed between the acetabular rim
      and the femoral neck causing degeneration and ossification. Both cam and pincer
      impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing
      impingement and rarely occurs alone.

PMID- 15972924
TI  - A histological study of articular cartilage after rotational acetabular osteotomy
      for hip dysplasia.
AB  - Acetabular dysplasia was produced in 24 immature white rabbits. A rotational
      acetabular osteotomy was then carried out and radiological and histological
      studies of the articular cartilage were made. In the hips which did not undergo
      osteotomy, radiographs at 26 weeks showed that residual subluxation remained and
      arthritic changes such as narrowing of the joint space or dislocation were still
      seen. However, in the operated group there was a remarkable increase in cover,
      but arthritic changes were not observed. After 24 weeks, the Mankin grading score
      in the operated group was significantly lower than that in the non-operated
      group. The latter hips showed an irregular surface of the cartilage, exfoliation
      and proliferation of synovial tissue. In those undergoing osteotomy, primary
      cloning of chondrocytes or hypercellularity was seen and at 24 weeks after
      operation and metaplasia of the cartilage in the fibrous tissue was observed in
      the boundary between the medial area of the acetabulum and the acetabular fossa.

PMID- 15972926
TI  - The management of slipped capital femoral epiphysis.

PMID- 15972928
TI  - Acetabular dysplasia after treatment for developmental dysplasia of the hip.

PMID- 15972930
TI  - Foot function after subtalar distraction bone block arthrodesis.

PMID- 15972931
TI  - Increasing response to mailed questionnaires by including a pencil/pen.
AB  - Nonmonetary incentives lead to small increases in response rates to mailed
      questionnaires. However, inclusion of a pen or pencil, which may be a
      facilitating factor as well as a reward, has not been shown to improve response
      to health surveys in prior trials. In 2001 and 2002, the authors conducted two US
      trials in which a study-logo pen or pencil was randomly included in a second
      questionnaire mailed to nonresponders to a first mailing. In the first study, of
      10,686 nonresponders to a cohort recruitment mailing, response to the second
      mailing was 55% with inclusion of a pen versus 40% without one (p < 0.001). In
      the second study, of 141 nonresponders to a pilot follow-up survey conducted 2
      years after entry into a cohort, response was 43% with inclusion of a pencil
      versus 24% without one (p = 0.02). This 15-19 percentage point increase for
      mailing 2 translated to a 5-6 percentage point increase after the two mailings
      combined. In a simulated study of three mailings based on these studies, the
      overall response rate increased by 4 percentage points at no added cost through
      inclusion of a pencil in the second mailing. The additional cost of the pencil
      was compensated for by the reduced number of nonrespondents sent packets at the
      third mailing. This study supports including a study-logo pen or pencil in a
      second questionnaire mailing to nonrespondents as a cost-effective method of
      increasing response rates.

PMID- 15972932
TI  - Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case
      Control Surveillance Study revisited.
AB  - Several studies have suggested that use of nonsteroidal antiinflammatory drugs
      (NSAIDs) may reduce the risk of breast cancer. Reductions in risk may vary
      according to the hormone receptor status of the tumor or the type of NSAID used.
      The authors extended a previous US hospital-based case-control study (the Case
      Control Surveillance Study) to include 444 additional cases, for a total of 7,006
      incident breast cancer cases (1976-2002). They examined the relation between
      regular NSAID use and breast cancer risk using logistic regression to adjust for
      confounding. The odds ratio for regular use of NSAIDs was 0.78 (95% confidence
      interval: 0.63, 0.97), and a trend of decreasing risk with increasing duration of
      use was statistically significant (p for trend = 0.02). The inverse association
      with regular use of NSAIDs was stronger among premenopausal women (odds ratio =
      0.62). The overall odds ratios for regular use of aspirin and ibuprofen were 0.86
      and 0.85, respectively. The effect of NSAID use on breast cancer risk did not
      vary according to the hormone receptor status of the tumor. In conclusion, long
      term regular use of NSAIDs was associated with decreased risk of breast cancer.
      The type of NSAID used or the hormone receptor status of the tumor did not modify
      the effect.

PMID- 15972933
TI  - The effect of wrist guard use on upper-extremity injuries in snowboarders.
AB  - The objective of this investigation was to determine the effect of wrist guard
      use on all upper-extremity injuries in snowboarders. This matched case-control
      study was conducted at 19 ski areas in Quebec, Canada. Cases were 1,066 injured
      snowboarders who reported upper-extremity injuries to the ski patrol during the
      2001-2002 season. Controls were 970 snowboarders with non-upper-extremity
      injuries who were matched to cases on ski area and the nearest date, age, and
      sex, in that order. The response rate was 71.8% (73.5% for cases and 70.1% for
      controls). Cases were compared with controls with regard to wrist guard use. The
      prevalence of wrist guard use among snowboarders with hand, wrist, or forearm
      injuries was 1.6%; for those with elbow, upper arm, or shoulder injuries, it was
      6.3%; and for controls, it was 3.9%. Thus, wrist guard use reduced the risk of
      hand, wrist, or forearm injury by 85% (adjusted odds ratio = 0.15, 95% confidence
      interval: 0.05, 0.45). However, the adjusted odds ratio for elbow, upper arm, or
      shoulder injury was 2.35 (95% confidence interval: 0.70, 7.81). These results
      provide evidence that use of wrist guards reduces the risk of hand, wrist, and
      forearm injuries but may increase the risk of elbow, upper arm, and shoulder
      injuries.

PMID- 15972934
TI  - Low toenail chromium concentration and increased risk of nonfatal myocardial
      infarction.
AB  - Chromium intake may increase insulin sensitivity, glucose tolerance, and the
      ratio of high density lipoprotein cholesterol to low density lipoprotein
      cholesterol. However, the epidemiologic evidence on the association between
      chromium and cardiovascular disease is very limited. To determine whether low
      toenail chromium concentrations were associated with risk of nonfatal myocardial
      infarction, the authors conducted an incident, population-based, case-control
      study in eight European countries and Israel in 1991-1992. Cases (n = 684) were
      men with a first diagnosis of myocardial infarction recruited from the coronary
      units of participating hospitals. Controls (n = 724) were men selected randomly
      from population registers (five study centers) or through other sources, such as
      hospitalized patients (three centers), general practitioners' practices (one
      center), or relatives or friends of cases (one center). Toenail chromium
      concentration was assessed by neutron activation analysis. Average toenail
      chromium concentrations were 1.10 mug/g in cases (95% confidence interval: 1.01,
      1.18) and 1.30 mug/g in controls (95% CI: 1.21, 1.40). Multivariate odds ratios
      for quintiles 2-5 were 0.82 (95% CI: 0.52, 1.31), 0.68 (95% CI: 0.43, 1.08), 0.60
      (95% CI: 0.37, 0.97), and 0.59 (95% CI: 0.37, 0.95). Toenail chromium
      concentration was inversely associated with the risk of a first myocardial
      infarction in men. These results add to an increasing body of evidence that
      points to the importance of chromium for cardiovascular health.

PMID- 15972935
TI  - Predictors of self-reported confidence ratings for adult recall of early life sun
      exposure.
AB  - Use of self-reported confidence ratings may be an efficient method for assessing
      recall bias. In this exploratory application of the method, the authors examined
      the relation between case-control status and self-reported confidence ratings. In
      2002 and 2003, melanoma cases (n = 141) and controls (n = 143) aged 20-44 years
      residing in Ontario, Canada, estimated the amounts of time they had spent
      outdoors in summer activities when they were 6-18 years of age and indicated
      their confidence in the accuracy of each estimate. The generalized estimating
      equations extension of logistic regression was used to examine dichotomized
      confidence ratings (more confident vs. less confident) for activities reported
      for ages 6-11 years and 12-18 years. Types of activity were associated with more
      confident reporting for both age strata; as the number of stable outdoor activity
      periods (total number of similar outdoor periods within each activity) reported
      by respondents increased, confidence decreased. Cumulative time spent outdoors
      was also associated with more confidence but reached statistical significance
      only for the age stratum 12-18 years. There was no statistically significant
      association between case-control status and self-reported confidence for either
      age stratum (6-11 years: odds ratio = 0.91; 12-18 years: odds ratio = 1.32),
      which suggests an absence of recall bias for reported time spent outdoors.

PMID- 15972936
TI  - Underascertainment of deaths using social security records: a recommended
      solution to a little-known problem.
AB  - Complete and accurate ascertainment of vital status is of great importance in
      cohort studies. Recently, during the vital status ascertainment phase of an
      ongoing occupational mortality study, the authors discovered a potentially
      serious problem with use of the Pension Benefit Information Company's tracing
      service or any tracing that relies on records from the Social Security
      Administration (SSA) Death Master File to identify deaths. Their investigation
      revealed that a number of US states restrict the information in the SSA's Death
      Master File that is available to researchers and the public as a source of death
      information. As a result of these findings, the authors recommend a revised two
      stage vital status tracing protocol. For stage I, data on all subjects for whom
      vital status is unconfirmed should be sent to the SSA. For stage II, information
      on all subjects to whom SSA assigned an unknown vital status as well as all
      subjects whom SSA identified as known decedents should be submitted to the
      National Death Index. This new protocol will enable researchers to maximize vital
      status ascertainment while containing costs associated with death identification.

PMID- 15972938
TI  - Re: "Ethics and sample size".

PMID- 15972939
TI  - Comparison of a spatial perspective with the multilevel analytical approach in
      neighborhood studies: the case of mental and behavioral disorders due to
      psychoactive substance use in Malmo, Sweden, 2001.
AB  - Most studies of neighborhood effects on health have used the multilevel approach.
      However, since this methodology does not incorporate any notion of space, it may
      not provide optimal epidemiologic information when modeling variations or when
      investigating associations between contextual factors and health. Investigating
      mental disorders due to psychoactive substance use among all 65,830 individuals
      aged 40-59 years in 2001 in Malmo, Sweden, geolocated at their place of
      residence, the authors compared a spatial analytical perspective, which builds
      notions of space into hypotheses and methods, with the multilevel approach.
      Geoadditive models provided precise cartographic information on spatial
      variations in prevalence independent of administrative boundaries. The multilevel
      model showed significant neighborhood variations in the prevalence of substance
      related disorders. However, hierarchical geostatistical models provided
      information on not only the magnitude but also the scale of neighborhood
      variations, indicating a significant correlation between neighborhoods in close
      proximity to each other. The prevalence of disorders increased with neighborhood
      deprivation. Far stronger associations were observed when using indicators
      measured in spatially adaptive areas, centered on residences of individuals,
      smaller in size than administrative neighborhoods. In neighborhood studies,
      building notions of space into analytical procedures may yield more comprehensive
      information than heretofore has been gathered on the spatial distribution of
      outcomes.

PMID- 15972940
TI  - Genetics of leptin and obesity: a HuGE review.
AB  - Leptin is an important regulator of the mass of adipose tissue and of body
      weight; it operates by inhibiting food intake and stimulating energy expenditure.
      Some polymorphic genes involved in the regulation of leptin-the leptin gene (LEP
      A19G), the leptin receptor gene (LEPR Q223R, K109R, and K656N), and the
      peroxisome proliferator-activated receptor-gamma gene (PPARG P12A and C161T)-
      have been investigated as possible factors associated with obesity. Allelic
      frequencies of these polymorphisms show ethnic variation. The authors performed a
      meta-analysis of the available data on the association between these
      polymorphisms and obesity based on case-control studies. Odds ratios and 95%
      confidence intervals for obesity associated with leptin polymorphisms were
      calculated by using both fixed- and random-effects models. Results suggest no
      evidence of association between the genes under study and obesity. The lack of
      association could be due to the complex pathogenesis of obesity, which involves a
      number of genetic and environmental factors. Large studies including testing of
      multiple genes in both obese and lean subjects, with epidemiologic data on
      dietary habits in different ethnic groups, are necessary to better understand the
      role of leptin in regulating weight in human populations.

PMID- 15972941
TI  - Preterm birth: the interaction of traffic-related air pollution with economic
      hardship in Los Angeles neighborhoods.
AB  - Preterm birth may be affected by the interaction of residential air pollution
      with neighborhood economic hardship. The authors examined variations in traffic
      related pollution exposure--measured by distance-weighted traffic density--using
      a framework reflecting the social and physical environments. An adverse social
      environment was conceptualized as low socioeconomic status (SES) neighborhoods-
      census tracts with concentrated poverty, unemployment, and dependence on public
      assistance. An adverse physical environment was depicted by the winter season,
      when thermal inversions trap motor vehicle pollutants, thereby increasing traffic
      related air pollution. Los Angeles County, California, birth records from 1994 to
      1996 were linked to traffic counts, census data, and ambient air pollution
      measures. The authors fit multivariate logistic models of preterm birth,
      stratified by neighborhood SES and third pregnancy trimester season. Traffic
      related air pollution exposure disproportionately affected low SES neighborhoods
      in the winter. Further, in these poorer neighborhoods, the winter season
      evidenced increased susceptibility among women with known risk factors. Health
      insurance was most beneficial to women residing in neighborhoods exposed to
      economic hardship and an adverse physical environment. Reducing preterm births
      warrants a concerted effort of social, economic, and environmental policies,
      focused on not only individual risk factors but also the reduction of localized
      air pollution, expansion of health-care coverage, and improvement of neighborhood
      resources.

PMID- 15972942
TI  - Studying time to pregnancy by use of a retrospective design.
AB  - Biologic fertility can be measured using time to pregnancy (TTP). Retrospective
      designs, although lacking detailed timed information about behavior and exposure,
      are useful since they have a well-defined target population, often have good
      response rates, and are simpler and less expensive to conduct than prospective
      studies. This paper reviews retrospective TTP studies from a methodological
      viewpoint and shows how methodological problems can be avoided or minimized by
      appropriate study design, conduct, and analysis. Sensitivity analyses using data
      from four European retrospective TTP studies are presented to explore the issues.
      Although the identified biases tend to have small impacts, the effects are not
      systematic across studies, and sensitivity analyses are recommended routinely.
      Planning bias can be checked by comparing propensity to report contraceptive
      failures in different exposure groups. Medical intervention bias can be avoided
      by censoring and inclusion of unsuccessful pregnancy attempts. Truncation bias
      can be a serious problem if unrecognized, but it is avoidable with appropriate
      study design and/or analysis. Behavior change bias can be minimized by assessing
      the covariates at the beginning of unprotected intercourse. More complete
      inference is possible if the study design covers the whole population, not just
      those who achieve a pregnancy.

PMID- 15972944
TI  - Invited commentary: Sibship effects and a call for a comparative disease
      approach.

PMID- 15972945
TI  - Sibship characteristics and risk of allergic rhinitis and asthma.
AB  - Studying associations between sibship characteristics and allergic diseases in
      detail may contribute clues to their etiology. The authors studied associations
      between sibship characteristics and risk of self-reported allergic rhinitis and
      asthma among 31,145 pregnant women participating in a nationwide study in Denmark
      during 1997-2000. Increasing sibship size was associated with a decreased risk of
      allergic rhinitis and asthma with allergic rhinitis but not with asthma without
      allergic rhinitis. The protective effect of having older siblings was stronger
      than the protective effect of having younger siblings for both allergic rhinitis
      and asthma with allergic rhinitis. There was no association between interval to
      closest older or younger sibling and risk of allergic rhinitis or asthma with
      allergic rhinitis, while the risk of asthma without allergic rhinitis increased
      with intervals of 2 or more years compared with less than 2 years to the nearest
      older sibling. The protective effect of having siblings on the risk of asthma
      with allergic rhinitis could be explained by a protective effect of siblings on
      the risk of allergic rhinitis alone. In conclusion, our findings suggest that
      different etiologic mechanisms are involved for allergic rhinitis and asthma with
      respect to the effect of sibship characteristics. Furthermore, the findings that
      allergic rhinitis was associated with the number of younger siblings but not with
      the age interval to younger siblings support the hypothesis of an influence of
      postnatal mechanisms and suggest that these mechanisms may not necessarily be
      operating only in early life.

PMID- 15972946
TI  - Wnt signaling and orthopedic diseases.

PMID- 15972947
TI  - Protection against experimental autoimmune myocarditis is mediated by interleukin
      10-producing T cells that are controlled by dendritic cells.
AB  - Experimental autoimmune myocarditis (EAM) can be induced in the Lewis rat by
      cardiac myosin or its cryptic S2-16 peptide epitope (amino acids 1052 to 1076).
      To investigate cellular mechanisms and the role of antigen-presenting cells in
      regulation of myocarditis, we induced protection against EAM in Lewis rats by
      administration of S2-16 peptide in incomplete Freund's adjuvant (IFA). Protection
      to EAM was associated with activation of S2-16-reactive splenocytes secreting
      high levels of interleukin (IL)-10 and reduced levels of interferon-gamma and IL
      2. Adoptive transfer of S2-16:IFA-induced splenocytes producing IL-10 suppressed
      myocarditis induction in syngeneic recipients, suggesting their regulatory cell
      nature. However, exposure of S2-16:IFA-induced cells to inflammatory cytokine IL
      12 converted them to Th1 effectors that transferred EAM. Differentiated function
      of S2-16-reactive T cells in protected rats resulted from increased IL-10
      production by dendritic cells (DCs). Purified DCs from S2-16:IFA-treated rats
      promoted S2-16-reactive CD4+ T cells to produce increased IL-10 and reduced
      interferon-gamma. In addition, adoptive transfer of IL-10-producing DCs from S2
      16:IFA-treated rats also induced protection to EAM in recipient rats. These
      studies demonstrated DCs and key cytokines, such as IL-10 and IL-12, regulated
      the fate of T cells in myocarditis development in the Lewis rat.

PMID- 15972948
TI  - Cardiac metallothionein synthesis in streptozotocin-induced diabetic mice, and
      its protection against diabetes-induced cardiac injury.
AB  - Oxidative stress is involved in the pathogenesis of diabetes and its
      cardiovascular complications. Metallothionein (MT), a stress-response protein, is
      significantly increased in the liver and kidney of diabetic animals. We examined
      whether diabetes also induces cardiac MT synthesis through oxidative damage and
      whether MT overexpression protects the heart from injury. Diabetes was induced in
      mice by single injection of streptozotocin (STZ), and cardiac MT mRNA and protein
      levels were measured 2 weeks and 2 months after STZ treatment. Diabetes
      significantly increased cardiac MT synthesis 2 weeks and 2 months after STZ
      treatment, with no change in cardiac metals including zinc, copper, and iron.
      Serum and cardiac vasopeptide endothelin and inflammatory cytokine tumor necrosis
      factor-alpha were also significantly increased in diabetic hearts, as were the
      ratio of oxidized to reduced glutathione and the immunohistochemical staining of
      3-nitrotyrosine and 4-hydroxynonenal. To explore the biological importance of
      increased MT synthesis in the heart, MT-overexpressing transgenic mice were
      treated with STZ and then examined 2 months later. A loss of inotropic reserve,
      uncovered during beta-adrenergic stimulation, and the presence of cardiac
      fibrosis, shown by increased Sirius red staining of collagen, were evident in the
      wild-type diabetic mice but not in the MT-overexpressing transgenic diabetic
      mice. These results suggest that diabetes-induced cardiac MT expression likely
      associates with systemic increases in endothelin-1 and tumor necrosis factor
      alpha and the resulting cardiac oxidative stress. Overexpressing cardiac MT
      significantly protects the heart from diabetes-induced injury.

PMID- 15972949
TI  - Inhibition of macrophage nuclear factor-kappaB leads to a dominant anti
      inflammatory phenotype that attenuates glomerular inflammation in vivo.
AB  - Infiltrating macrophages (mphi) can cause injury or facilitate repair, depending
      on how they are activated by the microenvironment. Studies in vitro have defined
      the roles of individual cytokines and signaling pathways in activation, but
      little is known about how macrophages integrate the multiple signals they receive
      in vivo. We inhibited nuclear factor-kappaB in bone marrow-derived macrophages
      (BMDMs) by using a recombinant adenovirus expressing dominant-negative IkappaB
      (Ad-IkappaB). This re-orientated macrophage activation so they became profoundly
      anti-inflammatory in settings where they would normally be classically activated.
      In vitro, the lipopolysaccharide-induced nitric oxide, interleukin-12, and tumor
      necrosis factor-alpha synthesis was abrogated while interleukin-10 synthesis
      increased. In vivo, fluorescently labeled BMDMs transduced with Ad-IkappaB and
      injected into the renal artery significantly reduced inducible nitric oxide
      synthase and MHC class II expression when activated naturally in glomeruli of
      rats with nephrotoxic nephritis. Furthermore, although they only comprised 15% of
      glomerular macrophages, their presence significantly reduced glomerular
      infiltration and activation of host macrophages. Injury in nephrotoxic nephritis
      was also decreased when assessed morphologically and by severity of albuminuria.
      The results demonstrate the power of Ad-IkappaB-transduced BMDMs to inhibit
      injury when activated by acute immune-mediated inflammation within the
      glomerulus.

PMID- 15972950
TI  - The role of neutrophils in the induction of glomerulonephritis by anti
      myeloperoxidase antibodies.
AB  - In humans, circulating anti-neutrophil cytoplasm autoantibodies (ANCAs) with
      specificity for myeloperoxidase (MPO) are strongly associated with the
      development of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN).
      In mice, we have demonstrated that intravenous injection of mouse antibodies
      specific for mouse MPO induces NCGN that closely mimics the human disease. We now
      report that the development of NCGN in this experimental model is accompanied by
      glomerular accumulation of neutrophils and macrophages. Neutrophil infiltration
      was most conspicuous at sites of glomerular necrosis and crescent formation, with
      macrophages also most numerous in crescents. Lymphocytes, however, were sparse in
      acute lesions. Importantly, mice that were depleted of circulating neutrophils
      with NIMP-R14 rat monoclonal antibodies were completely protected from anti-MPO
      IgG-induced NCGN. These findings provide direct evidence that neutrophils play a
      major role in the pathogenesis of anti-MPO-induced NCGN in this animal model and
      implicate neutrophils in the induction of human ANCA disease. This raises the
      possibility that therapeutic strategies to reduce circulating neutrophils could
      be beneficial to patients with ANCA-induced NCGN.

PMID- 15972951
TI  - Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by
      bacterial lipopolysaccharide: role of tumor necrosis factor-alpha.
AB  - Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and
      idiopathic pauci-immune necrotizing crescentic glomerulonephritis are associated
      with myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic autoantibodies
      (ANCAs). Clinical and experimental evidence indicates that ANCA and
      proinflammatory stimuli of infectious origin act synergistically to cause
      vasculitis. We tested this hypothesis in a recently developed mouse model of anti
      MPO IgG-induced glomerulonephritis by using bacterial lipopolysaccharide (LPS) as
      the proinflammatory stimulus. Systemic administration of LPS dose dependently
      increased renal injury induced by anti-MPO IgG as demonstrated by increased
      glomerular crescent formation and glomerular necrosis. In the early phase, LPS
      enhanced anti-MPO IgG-induced glomerular neutrophil accumulation. Furthermore, a
      transient induction of circulating tumor necrosis factor (TNF)-alpha levels,
      followed by a marked increase in circulating MPO levels, was observed on
      administration of LPS. In vitro, anti-MPO IgG induced a respiratory burst in
      murine neutrophils only after priming with TNF-alpha. Finally, anti-TNF-alpha
      treatment attenuated, but did not prevent, the LPS-mediated aggravation of anti
      MPO IgG-induced glomerulonephritis. In conclusion, our study demonstrates that
      ANCA and proinflammatory stimuli act synergistically to induce vasculitic disease
      and suggests potential benefits of inhibiting TNF-alpha bioactivity in treating
      human ANCA-associated necrotizing crescentic glomerulonephritis.

PMID- 15972952
TI  - Molecular pathogenesis of chronic wounds: the role of beta-catenin and c-myc in
      the inhibition of epithelialization and wound healing.
AB  - Lack of understanding of the molecular mechanisms and pathogenesis of impaired
      healing in chronic ulcers is a serious health issue that contributes to excessive
      limb amputations and mortality. Here we show that beta-catenin and its downstream
      targets in keratinocytes, c-myc, and keratins K6 and K16, play important roles in
      the development of chronic wounds. In contrast to normal epidermis, we observed a
      significant nuclear presence of beta-catenin and elevated c-myc expression at the
      nonhealing wound edge of chronic ulcers from 10 patients. In vitro studies
      indicated that stabilization of nuclear beta-catenin inhibited wound healing and
      keratinocyte migration by blocking epidermal growth factor response, inducing c
      myc and repressing the K6/K16 keratins (cytoskeletal components important for
      migration). The molecular mechanism of K6/K16 repression involved beta-catenin
      and arginine methyltransferase (CARM-1) acting as co-repressors of glucocorticoid
      receptor monomers. We conclude that activation of the beta-catenin/c-myc
      pathway(s) contributes to impaired healing by inhibiting keratinocyte migration
      and altering their differentiation. The presence of activated beta-catenin and c
      myc in the epidermis of chronic wounds may serve as a molecular marker of
      impaired healing and may provide future targets for therapeutic intervention.

PMID- 15972953
TI  - Tenascin-C regulates recruitment of myofibroblasts during tissue repair after
      myocardial injury.
AB  - Tenascin-C (TN-C) is an extracellular matrix molecule that is expressed during
      wound healing in various tissues. Although not detectable in the normal adult
      heart, it is expressed under pathological conditions. Previously, using a rat
      model, we found that TN-C was expressed during the acute stage after myocardial
      infarction and that alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts
      appeared in TN-C-positive areas. In the present study, we examined whether TN-C
      controls the dynamics of myofibroblast recruitment and wound healing after
      electrical injury to the myocardium of TN-C knockout (TNKO) mice compared with
      wild-type (WT) mice. In TNKO mice, myocardial repair seemed to proceed normally,
      but the appearance of myofibroblasts was delayed. With cultured cardiac
      fibroblasts, TN-C significantly accelerated cell migration, alpha-SMA expression,
      and collagen gel contraction but did not affect proliferation. Using recombinant
      fragments of murine TN-C, the functional domain responsible for promoting
      migration of cardiac fibroblasts was mapped to the conserved fibronectin type III
      (FNIII)-like repeats and the fibrinogen (Fbg)-like domain. Furthermore,
      alternatively spliced FNIII and Fbg-like domains proved responsible for the up
      regulation of alpha-SMA expression. These results indicate that TN-C promotes
      recruitment of myofibroblasts in the early stages of myocardial repair by
      stimulating cell migration and differentiation.

PMID- 15972954
TI  - Proteolysis of cell-surface tissue transglutaminase by matrix metalloproteinase-2
      contributes to the adhesive defect and matrix abnormalities in thrombospondin-2
      null fibroblasts and mice.
AB  - Thrombospondin (TSP)-2-null dermal fibroblasts display an attachment defect that
      results from increased matrix metalloproteinase (MMP)-2 levels in their
      conditioned media. To investigate the molecular mechanisms responsible for this
      defect, we analyzed the activity of tissue transglutaminase (tTG) in TSP-2-null
      dermal fibroblasts and in tissues of TSP-2-null mice. tTG functions as a co
      receptor for beta1 and beta3 integrins and stabilizes extracellular matrix
      proteins by introduction of isopeptide cross-links. Cell-surface tTG activity was
      reduced in TSP-2-null cells (0.50 +/- 0.05 arbitrary units versus 0.84 +/- 0.07
      for wild type; P < or = 0.05), and addition of MMP-2 to the culture medium of
      wild-type cells caused a 35% reduction in cell-surface tTG activity. tTG was
      susceptible to proteolysis by MMP-2 in vitro, and addition of the MMP inhibitor
      TIMP-2 to TSP-2-null cells restored tTG activity (0.3 +/- 0.08 for untreated
      cells; 0.71 +/- 0.09 with TIMP-2). TSP-2-null mice had reduced tTG activity in
      skin, as measured by incorporation of fluorescein isothiocyanate-labeled
      cadaverine, and a threefold increase in acetic acid-extracted dermal collagen.
      Furthermore, isopeptide cross-links were reduced in both uninjured skin and in
      excisional wounds of TSP-2-null mice, as determined by morphometric
      immunohistochemical analysis, indicating that isopeptide cross-links are
      important for the stabilization of the collagenous matrix in dermis. These
      findings provide a mechanism for the reduced adhesion of TSP-2-null fibroblasts
      and an explanation for the increased collagen solubility and fragility of TSP-2
      null skin.

PMID- 15972955
TI  - X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for
      ocular surface disease and resultant blindness.
AB  - X-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by
      mutations in the (EDA) gene, which is required for the morphogenesis of ectoderm
      derived tissues. Although EDA function in skin appendage development has been
      studied in Eda mutant "Tabby" mice, we have recently identified characteristic
      abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of
      eyes of Tabby males revealed that 1) as previously reported, mice lacked
      meibomian glands; 2) >80% developed corneal lesions such as neovascularization,
      keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and
      3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when
      housed in a standard environment. Strikingly, both corneal defects and
      inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1
      isoform, but meibomian glands were restored little if at all. These findings
      suggest that intact ocular surface health is EDA dependent and that Tabby corneal
      abnormalities are not solely dependent on meibomian gland lipid secretion.
      Alternatively, susceptibility to inflammation and other phenotypes could result
      from failure of the usual EDA receptor to activate nuclear factor-kappaB
      transcription factors. This can be further tested in Tabby and Tabby-EDA
      transgenic mice, which provide unique models of severe ocular surface disease.

PMID- 15972956
TI  - Expression profiles and functional analyses of Wnt-related genes in human joint
      disorders.
AB  - Rheumatoid arthritis (RA) and osteoarthritis (OA) are joint disorders that cause
      major public health problems. Previous studies of the etiology of RA and OA have
      implicated Wnt genes, although the exact nature of their involvement remains
      unclear. To further clarify the relationship between RA, OA, and the Wnt gene
      family, gene expression analyses were performed on articular cartilage, bone, and
      synovial tissues in knee joints taken from RA, OA, and nor-mal/control patients.
      Cytokine assays were also performed in cells transfected with Wnt-7b, a member of
      the gene family most closely linked to RA and OA. Of the human Wnt genes, real
      time PCR analysis revealed significant up-regulation of Wnt-7b in OA cartilage
      and RA synovium. In situ hybridization and immunohistochemistry also revealed
      that Wnt-7b was present in articular cartilage, bone, and synovium of RA samples
      and in osteophytes, articular cartilage, bone marrow, and synovium of OA samples.
      The levels of the cytokines tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6 were significantly increased in RA synovium and Wnt-7b-transfected
      normal synovial cells when compared with normal samples. These results point to
      the potential involvement of Wnt signaling in the pathobiology of both RA and OA.

PMID- 15972957
TI  - Aberrant beta-catenin signaling in tuberous sclerosis.
AB  - The pathology associated with tuberous sclerosis complex (TSC) shows diverse
      phenotypes that suggest abnormal signaling of multiple pathways. Besides the
      negative regulatory role of the TSC1/TSC2 proteins on mTOR, we have reported an
      effect on beta-catenin signaling at the level of the degradation complex in
      vitro. The TSC1/TSC2 complex associates with GSK3 and Axin and promotes beta
      catenin degradation to inhibit Wnt-stimulated TCF/LEF-dependent transcription.
      Here, we show that beta-catenin and its effectors, cyclin D1 and connexin 43,
      were up-regulated in TSC-related angiomyolipomas and lymphangioleiomyomatosis.
      This was supported by the failure of three disease-causing TSC2 missense mutants
      to inhibit Wnt signaling. Further, the interaction between TSC1/TSC2 and
      components of the beta-catenin degradation complex was dependent on Wnt
      stimulation such that binding of tuberin to GSK3 and Axin was reduced in the
      presence of Wnt whereas the tuberin-Dishevelled interaction was increased. GSK3
      activity played a role in regulating the assembly/stability of the degradation
      complex. Inhibition of GSK3 by lithium chloride reduced its association with TSC1
      whereas disruption of GSK3-phosphorylation sites in TSC1 reduced interaction
      between TSC2 and TSC1. Collectively, our data provide further evidence that beta
      catenin signaling plays a role in TSC pathogenesis in vivo and suggest a novel
      role of GSK3 in modulating the TSC1/TSC2 complex through TSC1 phosphorylation.

PMID- 15972958
TI  - Molecular profiling of giant cell tumor of bone and the osteoclastic localization
      of ligand for receptor activator of nuclear factor kappaB.
AB  - Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm
      comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells,
      which cause bony destruction, are thought to be recruited from normal monocytic
      pre-osteoclasts by stromal cell expression of the ligand for receptor activator
      of nuclear factor kappaB (RANKL). This model forms the foundation for clinical
      trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression
      profiling, we identified both osteoblast and osteoclast signatures within GCTs,
      including key regulators of osteoclast differentiation and function such as
      RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex
      vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly
      found that RANKL mRNA and protein were more highly expressed in osteoclasts than
      in stromal cells, as determined by expression profiling, flow cytometry,
      immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The
      expression patterns of molecules implicated in signaling between stromal cells
      and monocytic osteoclast precursors were analyzed in both primary and
      fractionated GCTs. Finally, using array-based comparative genomic hybridization,
      neither GCTs nor the derived stromal cells demonstrated significant genomic gains
      or losses. These data raise questions regarding the role of RANKL in GCTs that
      may be relevant to the development of molecularly targeted therapeutics for this
      disease.

PMID- 15972959
TI  - Increased toll-like receptor 4 expression in thymus of myasthenic patients with
      thymitis and thymic involution.
AB  - Thymic abnormalities are present in approximately 80% of myasthenia gravis (MG)
      patients, and the thymus seems to be the main site of autosensitization to the
      acetylcholine receptor. In view of findings that the innate immune system can
      generate an autoimmune response, we studied the expression of Toll-like receptors
      (TLRs) 2 to 5, key components of innate immunity signaling pathways, in 37
      thymuses from patients with autoimmune MG. TLR4 mRNA levels were significantly
      greater in thymitis (hyperplasia with diffuse B-cell infiltration) and involuted
      thymus than in germinal center hyperplasia and thymoma. By immunohistochemistry
      and confocal microscopy, cells positive for TLR4 protein were rarely detected in
      thymoma. However, in thymitis TLR4 protein was mostly found on epitheliomorphic
      (cytokeratin-positive) cells located in close association with clusters of
      acetylcholine receptor-positive myoid cells in thymic medulla and also at the
      borders between cortical and medullary areas. B cells were never TLR4-positive.
      TLR4 protein was also present in remnant tissue of involuted thymus. This is the
      first finding of a possible link between innate immunity and MG. We speculate
      that in a subgroup of MG patients, an exogenous or endogenous danger signal may
      activate the innate immune system and give rise to TLR4-mediated mechanisms
      contributing to autoimmunity.

PMID- 15972960
TI  - Blocking of interleukin-17 during reactivation of experimental arthritis prevents
      joint inflammation and bone erosion by decreasing RANKL and interleukin-1.
AB  - Rheumatoid arthritis is characterized by an intermittent course of disease with
      alternate periods of remission and relapse. T cells, and in particular the T-cell
      cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares.
      Here, we report that neutralizing endogenous IL-17 during reactivation of antigen
      induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17
      mRNA expression was clearly up-regulated during primary arthritis and was further
      enhanced after antigen rechallenge. Neutralization of IL-17 significantly
      prevented joint swelling at day 1 of flare and significantly suppressed joint
      inflammation and cartilage proteoglycan depletion at day 4, as assessed by
      histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a
      marker of osteoclast-like activity, and synovial RANKL mRNA expression were both
      suppressed. The degree of bone erosions strongly correlated with the severity of
      joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by
      suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial
      expression of both IL-1beta and tumor necrosis factor-alpha, whereas blocking IL
      1 did not affect tumor necrosis factor-alpha levels. These data indicate that IL
      17 is an important upstream mediator in joint pathology during flare-up of
      experimental arthritis.

PMID- 15972961
TI  - Perturbed neurogenesis in the adult hippocampus associated with presenilin-1
      A246E mutation.
AB  - In addition to its well-established role in gamma-secretase cleavage, presenilin
      (PS) also plays a role in regulating the stability of cytosolic beta-catenin, a
      protein involved in Wnt signaling. Several familial Alzheimer's disease
      associated PS1 mutations have been shown to increase the stability of the
      signaling pool of beta-catenin, correlating with enhanced cell proliferation.
      Accordingly, we hypothesized that in the setting of PS1 mutations, abnormal
      activation of Wnt/beta-catenin signaling leads to increased cell division. We
      tested this hypothesis by examining whether there is evidence of increased
      neurogenesis in the hippocampus of adult transgenic mice that overexpress the PS1
      A246E mutation. In PS1/PS2-deficient fibroblasts, expression of PS1 A246E
      Familial AD mutation failed to restore the rapid turnover of beta-catenin
      compared with wild-type PS1. We then examined whether the same mutation enhanced
      neurogenesis in vivo in adult hippocampus of PS1-deficient mice when restored by
      wild-type human PS1 (PS1(-/-)WT) or A246E PS1 mutation (PS1(-/-)AE). The PS1
      A246E mutation stimulated the proliferation of progenitor cells in the dentate
      gyrus of adult mice, as assessed by 5-bromo-2-deoxyuridine incorporation, but did
      not influence their survival or differentiation. These observations suggest that
      the PS1 A246E mutation influences cell growth putatively via abnormal beta
      catenin signaling in vivo.

PMID- 15972962
TI  - Age-related loss of synaptophysin immunoreactive presynaptic boutons within the
      hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice.
AB  - Neuron and synapse loss are important features of the neuropathology of
      Alzheimer's disease (AD). Recently, we observed substantial age-related
      hippocampal neuron loss in APP751SL/PS1M146L transgenic mice but not in PS1M146L
      mice. Here, we investigated APP751SL mice, PS1M146L mice, and APP751SL/PS1M146L
      mice for age-related alterations in synaptic integrity within hippocampal stratum
      moleculare of the dentate gyrus (SM), stratum lucidum of area CA3 (SL), and
      stratum radiatum of area CA1-2 (SR) by analyzing densities and numbers of
      synaptophysin-immunoreactive presynaptic boutons (SIPBs). Wild-type mice,
      APP751SL mice and PS1M146L mice showed similar amounts of age-related SIPB loss
      within SM, and no SIPB loss within SL. Both APP751SL mice and PS1M146L mice
      showed age-related SIPB loss within SR. Importantly, APP751SL/PS1M146L) mice
      displayed the severest age-related SIPB loss within SM, SL, and SR, even in
      regions free of extracellular Abeta deposits. Together, these mouse models offer
      a unique framework to study the impact of several molecular and cellular events
      caused by mutant APP and/or mutant PS1 on age-related alterations in synaptic
      integrity. The observation of age-related SIPB loss within SR of PS1M146L mice
      supports a role of mutant PS1 in neurodegeneration apart from its contribution to
      alterations in Abeta generation.

PMID- 15972963
TI  - Developmental abnormalities of neuronal structure and function in prenatal mice
      lacking the prader-willi syndrome gene necdin.
AB  - Necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental
      disorder Prader-Willi syndrome (PWS). Ndntm2Stw mutant mice die shortly after
      birth because of abnormal respiratory rhythmogenesis generated by a key medullary
      nucleus, the pre-Botzinger complex (preBotC). Here, we address two fundamental
      issues relevant to its pathogenesis. First, we performed a detailed anatomical
      study of the developing medulla to determine whether there were defects within
      the preBotC or synaptic inputs that regulate respiratory rhythmogenesis. Second,
      in vitro studies determined if the unstable respiratory rhythm in Ndntm2Stw mice
      could be normalized by neuromodulators. Anatomical defects in Ndntm2Stw mice
      included defasciculation and irregular projections of axonal tracts, aberrant
      neuronal migration, and a major defect in the cytoarchitecture of the
      cuneate/gracile nuclei, including dystrophic axons. Exogenous application of
      neuromodulators alleviated the long periods of slow respiratory rhythms and
      apnea, but some instability of rhythmogenesis persisted. We conclude that
      deficiencies in the neuromodulatory drive necessary for preBotC function
      contribute to respiratory dysfunction of Ndntm2Stw mice. These abnormalities are
      part of a more widespread deficit in neuronal migration and the extension,
      arborization, and fasciculation of axons during early stages of central nervous
      system development that may account for respiratory, sensory, motor, and
      behavioral problems associated with PWS.

PMID- 15972964
TI  - Uniform overexpression and rapid accessibility of alpha5beta1 integrin on blood
      vessels in tumors.
AB  - Integrin alpha5beta1 is among the proteins overexpressed on tumor vessels and is
      a potential target for diagnostics and therapeutics. Here, we mapped the
      distribution of alpha5beta1 integrin in three murine tumor models and identified
      sites of expression that are rapidly accessible to intravascular antibodies. When
      examined by conventional immunohistochemistry, alpha5beta1 integrin expression
      was strong on most blood vessels in RIP-Tag2 transgenic mouse tumors, adenomatous
      polyposis coli (apc) mouse adenomas, and implanted MCa-IV mammary carcinomas.
      Expression increased during malignant progression in RIP-Tag2 mice. However,
      immunoreactivity was also strong in normal pancreatic ducts, intestinal smooth
      muscle, and several other sites. To determine which sites of expression were
      rapidly accessible from the bloodstream, we intravenously injected anti
      alpha5beta1 integrin antibody and 10 minutes to 24 hours later examined the
      amount and distribution of labeling. The injected antibody strongly labeled tumor
      vessels at all time points but did not label most normal blood vessels or gain
      access to pancreatic ducts or intestinal smooth muscle. Intense vascular labeling
      by anti-alpha5beta1 integrin antibody co-localized with the uniform CD31
      immunoreactivity of tumor vessels and contrasted sharply with the patchy
      accumulation of nonspecific IgG at sites of leakage. This strategy of injecting
      antibodies revealed the uniform overexpression and rapid accessibility of
      alpha5beta1 integrin on tumor vessels and may prove useful in assessing other
      potential therapeutic targets in cancer.

PMID- 15972965
TI  - Biological role of anaplastic lymphoma kinase in neuroblastoma.
AB  - Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor originally
      identified as part of the chimeric nucleophosmin-ALK protein in the t(2;5)
      chromosomal rearrangement associated with anaplastic large cell lymphoma. We
      recently demonstrated that the ALK kinase is constitutively activated by gene
      amplification at the ALK locus in several neuroblastoma cell lines. Forming a
      stable complex with hyperphosphorylated ShcC, activated ALK modifies the
      responsiveness of the mitogen-activated protein kinase pathway to growth factors.
      In the present study, the biological role of activated ALK was examined by
      suppressing the expression of ALK kinase in neuroblastoma cell lines using an RNA
      interference technique. The suppression of activated ALK in neuroblastoma cells
      by RNA interference significantly reduced the phosphorylation of ShcC, mitogen
      activated protein kinases, and Akt, inducing rapid apoptosis in the cells. By
      immunohistochemical analysis, the cytoplasmic expression of ALK was detected in
      most of the samples of neuroblastoma tissues regardless of the stage of the
      tumor, whereas significant amplification of ALK was observed in only 1 of 85
      cases of human neuroblastoma samples. These data demonstrate the limited
      frequency of ALK activation in the real progression of neuroblastoma.

PMID- 15972966
TI  - Follicular thyroid tumors with the PAX8-PPARgamma1 rearrangement display
      characteristic genetic alterations.
AB  - Follicular thyroid carcinomas (FTC) arise through oncogenic pathways distinct
      from those involved in the papillary histotype. Recently, a t(2;3)(q13;p25)
      rearrangement, which juxtaposes the thyroid transcription factor PAX8 to the
      peroxisome proliferator-activated receptor (PPAR) gamma1, was described in FTCs.
      In this report, we describe gene expression in 11 normal tissues, 4 adenomas, and
      8 FTCs, with or without the PAX8-PPARgamma1 translocation, using custom 60-mer
      oligonucleotide microarrays. Results were confirmed by quantitative real-time
      polymerase chain reaction of 65 thyroid tissues and by immunohistochemistry.
      Statistical analysis revealed a pattern of 93 genes discriminating FTCs, with or
      without the translocation, that were morphologically undistinguishable. Although
      the expression of thyroid-specific genes was detectable, none appeared to be
      differentially regulated between tumors with or without the translocation.
      Differentially expressed genes included genes related to lipid/glucose/amino acid
      metabolism, tumorigenesis, and angiogenesis. Surprisingly, several PPARgamma
      target genes were up-regulated in PAX8-PPARgamma-positive FTCs such as
      angiopoietin-like 4 and aquaporin 7. Moreover many genes involved in PAX8
      PPARgamma expression profile presented a putative PPARgamma-promoter site,
      compatible with a direct activity of the fusion product. These data identify
      several differentially expressed genes, such as FGD3, that may serve as potential
      targets of PPARgamma and as members of novel molecular pathways involved in the
      development of thyroid carcinomas.

PMID- 15972967
TI  - The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is
      an early event during the multistep process of colon carcinogenesis.
AB  - Calcium accumulation in the endoplasmic reticulum is accomplished by
      sarco/endoplasmic reticulum calcium transport ATPases (SERCA enzymes). To better
      characterize the role of SERCA3 in colon carcinogenesis, its expression has been
      investigated in colonic epithelium, benign lesions, adenomas, and
      adenocarcinomas. In addition, the regulation of SERCA3 expression was analyzed in
      the context of the adenomatous polyposis coli/beta-catenin/T-cell factor 4 (TCF4)
      pathway and of specificity protein 1 (Sp1)-like factor-dependent transcription.
      We report that SERCA3 expression increased along the crypts as cells
      differentiated in normal colonic mucosa and in hyperplastic polyps, was
      moderately and heterogeneously expressed in colonic adenomas with expression
      levels inversely correlated with the degree of dysplasia, was barely detectable
      in well and moderately differentiated adenocarcinomas, and was absent in poorly
      differentiated tumors. Inhibition of Sp1-like factor-dependent transcription
      blocked SERCA3 expression during cell differentiation, and SERCA3 expression was
      induced by the expression of dominant-negative TCF4 in colon cancer cells. These
      data link SERCA3 expression to the state of differentiation of colonic epithelial
      cells, and relate SERCA3 expression, already decreased in adenomas, to enhanced
      adenomatous polyposis coli/beta-catenin/TCF4-dependent signaling and deficient
      Sp1-like factor-dependent transcription. In conclusion, intracellular calcium
      homeostasis becomes progressively anomalous during colon carcinogenesis as
      reflected by deficient SERCA3 expression.

PMID- 15972968
TI  - c-Fos-dependent induction of the small ras-related GTPase Rab11a in skin
      carcinogenesis.
AB  - Malignant transformation of mouse skin by tumor promoters and chemical
      carcinogens, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate
      (TPA), is a multistage process leading to the formation of squamous cell
      carcinomas. It has been shown that mice lacking the AP-1 family member c-Fos
      exhibit an impaired transition from benign to malignant skin tumors. Here, we
      demonstrate enhanced expression of the small Ras-related GTPase Rab11a after
      short-term TPA treatment of mouse back skin. Expression of Rab11a in vivo and in
      vitro critically depended on c-Fos, because TPA application to the back skin of c
      Fos-deficient mice and to mouse embryonic fibroblasts did not induce Rab11a mRNA
      or protein expression. Moreover, dexamethasone, which is a potent inhibitor of AP
      1-mediated transactivation that exhibits anti-inflammatory and anti-tumor
      promoting activities, inhibited TPA-induced expression of Rab11a. Within the
      Rab11a gene promoter, we identified a functional AP-1 binding element that
      exhibited elevated c-Fos binding activity after TPA treatment of keratinocytes.
      Enhanced expression was not restricted to chemically induced mouse skin tumors
      but was also found in tumor specimens derived from patients with epithelial skin
      tumors. These data identify Rab11a as a novel, tumor-associated c-Fos/AP-1 target
      and may point to an as yet unrecognized function of Rab11a in the development of
      skin cancer.

PMID- 15972970
TI  - The atheroprotective effect of 17beta-estradiol depends on complex interactions
      in adaptive immunity.
AB  - Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone
      apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak
      development of immunodeficient ApoE(-/-)/recombination activating gene 2 (RAG-2(
      /-)) double-deficient mice was insensitive to estradiol. In the present work, we
      demonstrate that the reconstitution of ApoE(-/-)/RAG-2(-/-) with bone marrow from
      immunocompetent ApoE(-/-)/RAG-2(+/+) mice restores the protective effect of
      estradiol on fatty streak constitution. We extended this demonstration to the
      model of low-density lipoprotein receptor-deficient mice, establishing the
      obligatory role of mature lymphocytes in this process. We then investigated
      whether the protective effect of estradiol was mediated by a specific lymphocyte
      subpopulation by studying the hormonal effect on fatty streak constitution in
      recently developed models of ApoE(-/-) mice deficient in selective T-lymphocyte
      subsets (either TCRalphabeta+, CD4+, CD8+, or TCRgammadelta+ lymphocytes) or B
      lymphocytes. In all these specifically immunodeficient mice, estradiol
      administration to ovariectomized mice conferred protection as in immunocompetent
      ApoE(-/-) mice, clearly demonstrating that no single lymphocyte subpopulation was
      specifically required for this effect. These results point to additional
      lymphocyte-dependent mechanisms such as modulating the interactions among
      lymphocytes and between lymphocytes and endothelial and/or antigen-presenting
      cells.

PMID- 15972969
TI  - Regulation of hepatocyte activator inhibitor-1 expression by androgen and
      oncogenic transformation in the prostate.
AB  - Hepatocyte activator inhibitor-1 (HAI-1) is a transmembrane serine protease
      inhibitor that regulates the conversion of latent to active hepatocyte growth
      factor (HGF). Studies supporting a role for the HGF pathway in prostate
      carcinogenesis prompted an analysis of HAI-1 expression in the prostate. Here we
      analyze the regulation of HAI-1 expression by androgen, oncogenic transformation,
      and cancer progression. Immunohistochemical analysis revealed that HAI-1
      expression was restricted to prostate epithelium, where staining occurred
      primarily in basal and atrophic luminal epithelial cells. Compared to normal
      glands, HAI-1 expression was significantly increased in localized prostate cancer
      and was present in most prostate cancer metastases. HAI-1 protein expression
      levels were sensitive to androgen in normal epithelium but not in cancer.
      Although androgen did not increase HAI-1 protein expression levels in LNCaP
      cells, it decreased HAI-1 surface expression, consistent with previous data from
      our group (Martin DB, Gifford DR, Wright ME, Keller A, Yi E, Goodlett DR,
      Aebersold R, Nelson PS: Quantitative proteomic analysis of proteins released by
      neoplastic prostate epithelium. Cancer Res 2004, 64:347-355). HAI-1
      overexpression in cancer was predictive of prostate-specific antigen recurrence
      (relative risk, 1.24). These results suggest that HAI-1 regulates the HGF Met
      axis on prostate epithelial cells and influences HGF mediated tumor invasion and
      metastasis.

PMID- 15972971
TI  - EGFL7 is a chemoattractant for endothelial cells and is up-regulated in
      angiogenesis and arterial injury.
AB  - The endothelium of the adult vasculature is normally quiescent, with the
      exception of the vasculature of the female reproductive system. However, in
      response to appropriate stimuli (ie, wound healing, atherosclerosis, tumor growth
      and metastasis, arthritis) the vasculature becomes activated and grows new
      capillaries through angiogenesis. We have recently identified a novel endothelial
      restricted gene, Egfl7, that encodes a 41-kd secreted protein (Fitch MJ,
      Campagnolo L, Kuhnert F, Stuhlmann H: Egfl7, a novel epidermal growth factor
      domain gene expressed in endothelial cells. Dev Dyn 2004, 230:316-324). Egfl7 is
      expressed at high levels early during mouse embryonic development and is strictly
      associated with the vascular bed. In this study, we investigated Egfl7 expression
      in the quiescent adult vasculature, in the pregnant uterus, and in two different
      models of arterial injury, namely ballooning and ferric chloride injury. By RNA
      in situ hybridization, Egfl7 expression in the vasculature was found to be
      restricted to the endothelium of the capillaries and mature vessels. In the
      pregnant uterus, increased vascularization was accompanied by up-regulation of
      Egfl7. On arterial injury, Egfl7 expression was up-regulated in the regenerating
      endothelium, but not in the neointima. Importantly, the EGFL7 protein acted as a
      chemoattractant for embryonic endothelial cells and fibroblasts in a cell
      migration assay. Together, these results suggest that Egfl7 functions in the
      formation and maintenance of endothelial integrity and that its up-regulation may
      be a critical component in the reorganization of the vascular bed in response to
      angiogenic stimuli.

PMID- 15972973
TI  - Pre-irradiation effects on ionization chambers used in radiation therapy.
AB  - Dosimetry protocols recommend that ionization chambers used in radiation therapy
      be pre-irradiated until they 'settle', i.e., until a stable reading is obtained.
      Previous reports have claimed that a lack of pre-irradiation could result in
      errors up to several per cent. Recently, data collected for a large number of
      commonly used ion chambers at the Institute for National Measurement Standards,
      NRC, Canada, have been collated and analysed, with additional data contributed by
      the National Physical Laboratory, UK. With this data set, it was possible to
      relate patterns of ion chamber behaviour to design parameters. While several
      mechanisms seem to contribute to this behaviour, the most obvious correlations
      implicate the type of insulator surrounding the central collector electrode, the
      extent of collector electrode shielding and possibly the area of the insulator
      exposed at the base of the active air volume. The results show that ion chambers
      with electrode connections guarded up to the active air volume settle quickly
      (approximately 9 min) and the change in response is small (less than
      approximately 0.2%). For ion chambers where the guard connection surrounding the
      central collector does not extend up to the active air volume, settling times of
      15-20 min and an associated change in response of up to 1% are typical. For some
      models of ion chambers, the irradiation rate may also play a role in settling
      behaviour. Settling times for the ion chambers studied here were found to be
      independent of beam quality.

PMID- 15972972
TI  - 13-cis retinoic acid inhibits development and progression of chronic allograft
      nephropathy.
AB  - Chronic allograft nephropathy is characterized by chronic inflammation and
      fibrosis. Because retinoids exhibit anti-proliferative, anti-inflammatory, and
      anti-fibrotic functions, the effects of low and high doses of 13-cis-retinoic
      acid (13cRA) were studied in a chronic Fisher344-->Lewis transplantation model.
      In 13cRA animals, independent of dose (2 or 20 mg/kg body weight/day) and start
      (0 or 14 days after transplantation) of 13cRA administration, serum creatinine
      was significantly lower and chronic rejection damage was dramatically reduced,
      including subendothelial fibrosis of preglomerular vessels and chronic
      tubulointerstitial damage. The number of infiltrating mononuclear cells and their
      proliferative activity were significantly diminished. The mRNA expression of
      chemokines (MCP-1/CCL2, MIP-1alpha/CCL3, IP-10/CXCL10, RANTES/CCL5) and proteins
      associated with fibrosis (plasminogen activator inhibitor-1, transforming growth
      factor-beta1, and collagens I and III) were strikingly lower in treated
      allografts. In vitro, activated peritoneal macrophages of 13cRA-treated rats
      showed a pronounced decrease in protein secretion of inflammatory cytokines (eg,
      tumor necrosis factor-alpha, interleukin-6). The suppression of the
      proinflammatory chemokine RANTES/CCL5 x 13cRA in fibroblasts could be mapped to a
      promoter module comprising IRF-1 and nuclear factor-kappaB binding elements, but
      direct binding of retinoid receptors to promoter elements could be excluded. In
      summary, 13cRA acted as a potent immunosuppressive and anti-fibrotic agent able
      to prevent and inhibit progression of chronic allograft nephropathy.

PMID- 15972974
TI  - Absorption spectra variations of EBT radiochromic film from radiation exposure.
AB  - Gafchromic EBT radiochromic film is one of the newest radiation-induced auto
      developing x-ray analysis films available for therapeutic radiation dosimetry in
      radiotherapy applications. The spectral absorption properties in the visible
      wavelengths have been investigated and results show two main peaks in absorption
      located at 636 nm and 585 nm. These absorption peaks are different to many other
      radiochromic film products such as Gafchromic MD-55 and HS film where two peaks
      were located at 676 nm and 617 nm respectively. The general shape of the
      absorption spectra is similar to older designs. A much higher sensitivity is
      found at high-energy x-rays with an average 0.6 OD per Gy variation in OD seen
      within the first Gy measured at 636 nm using 6 MV x-rays. This is compared to
      approximately 0.09 OD units for the first Gy at the 676 nm absorption peak for HS
      film at 6 MV x-ray energy. The film's blue colour is visually different from
      older varieties of Gafchromic film with a higher intensity of mid-range blue
      within the film. The film provides adequate relative absorbed dose measurement
      for clinical radiotherapy x-ray assessment in the 1-2 Gy dose range which with
      further investigation may be useful for fractionated radiotherapy dose
      assessment.

PMID- 15972975
TI  - Cardiac PET imaging in mice with simultaneous cardiac and respiratory gating.
AB  - Gating firmware and software were developed for the microPET II small animal
      scanner. The measured cardiac and respiratory signals were collected and
      converted to TTL gating signals by a Biopac MP150 data acquisition system and
      sent to microPET II through two BNC connectors on the front panel. During
      acquisition, the coincidence monitor takes the average of the last eight gate
      input cycles and inserts this into the list mode data stream on the falling edge
      of the gating pulse. This value is then used to determine the current time
      interval of the next gate cycle when the list mode data are sorted into
      sinograms. The gating firmware and software were validated by an experiment using
      a rotating point source. Mouse heart (18F-FDG) and bone (18F(-)) imaging was
      performed with simultaneous cardiac and respiratory gating. It was clearly
      demonstrated that the contractile function of the mouse heart can be studied by
      cardiac-gated imaging with microPET II. The left ventricular volumes at different
      times of the cardiac cycle were measured and the ejection fraction was
      calculated. In the bone scan, no detectable movement caused by heart contraction
      was observed. Respiratory motion was more subtle with virtually no motion for
      more than 75% of the respiratory cycle. The motion of the mouse heart and bones
      in the thorax caused by respiration was less than 1 mm. It appears with the
      current resolution of PET, and the small fraction of the respiratory cycle in
      which motion occurs, that respiratory gating is probably not necessary for most
      mouse cardiac studies.

PMID- 15972976
TI  - Human breast cancer in vitro: matching histo-pathology with small-angle x-ray
      scattering and diffraction enhanced x-ray imaging.
AB  - Twenty-eight human breast tumour specimens were studied with small-angle x-ray
      scattering (SAXS), and 10 of those were imaged by the diffraction enhanced x-ray
      imaging (DEI) technique. The sample diameter was 20 mm and the thickness 1 mm.
      Two examples of ductal carcinoma are illustrated by histology images, DEI, and
      maps of the collagen d-spacing and scattered intensity in the Porod regime, which
      characterize the SAXS patterns from collagen-rich regions of the samples. Histo
      pathology reveals the cancer-invaded regions, and the maps of the SAXS parameters
      show that in these regions the scattering signal differs significantly from
      scattering by the surrounding tissue, indicating a degradation of the collagen
      structure in the invaded regions. The DEI images show the borders between
      collagen and adipose tissue and provide a co-ordinate system for tissue mapping
      by SAXS. In addition, degradation of the collagen structure in an invaded region
      is revealed by fading contrast of the DEI refraction image. The 28 samples
      include fresh, defrosted tissue and formalin-fixed tissue. The d-values with
      their standard deviations are given. In the fresh samples there is a systematic
      0.76% increase of the d-value in the invaded regions, averaged over 11 samples.
      Only intra-sample comparisons are made for the formalin-fixed samples, and with a
      long fixation time, the difference in the d-value stabilizes at about 0.7%. The
      correspondence between the DEI images, the SAXS maps and the histo-pathology
      suggests that definitive information on tumour growth and malignancy is obtained
      by combining these x-ray methods.

PMID- 15972977
TI  - Use of the isolated problem approach for multi-compartment BEM models of electro
      magnetic source imaging.
AB  - The isolated problem approach (IPA) is a method used in the boundary element
      method (BEM) to overcome numerical inaccuracies caused by the high-conductivity
      difference in the skull and the brain tissues in the head. Hamalainen and Sarvas
      (1989 IEEE Trans. Biomed. Eng. 36 165-71) described how the source terms can be
      updated to overcome these inaccuracies for a three-layer head model. Meijs et al
      (1989 IEEE Trans. Biomed. Eng. 36 1038-49) derived the integral equations for the
      general case where there are an arbitrary number of layers inside the skull.
      However, the IPA is used in the literature only for three-layer head models.
      Studies that use complex boundary element head models that investigate the
      inhomogeneities in the brain or model the cerebrospinal fluid (CSF) do not make
      use of the IPA. In this study, the generalized formulation of the IPA for multi
      layer models is presented in terms of integral equations. The discretized version
      of these equations are presented in two different forms. In a previous study
      (Akalin-Acar and Gencer 2004 Phys. Med. Biol. 49 5011-28), we derived
      formulations to calculate the electroencephalography and magnetoencephalography
      transfer matrices assuming a single layer in the skull. In this study, the
      transfer matrix formulations are updated to incorporate the generalized IPA. The
      effects of the IPA are investigated on the accuracy of spherical and realistic
      models when the CSF layer and a tumour tissue are included in the model. It is
      observed that, in the spherical model, for a radial dipole 1 mm close to the
      brain surface, the relative difference measure (RDM*) drops from 1.88 to 0.03
      when IPA is used. For the realistic model, the inclusion of the CSF layer does
      not change the field pattern significantly. However, the inclusion of an
      inhomogeneity changes the field pattern by 25% for a dipole oriented towards the
      inhomogeneity. The effect of the IPA is also investigated when there is an
      inhomogeneity in the brain. In addition to a considerable change in the scale of
      the potentials, the field pattern also changes by 15%. The computation times are
      presented for the multi-layer realistic head model.

PMID- 15972978
TI  - Representation of bioelectric current sources using Whitney elements in the
      finite element method.
AB  - Bioelectric current sources of magneto- and electroencephalograms (MEG, EEG) are
      usually modelled with discrete delta-function type current dipoles, despite the
      fact that the currents in the brain are naturally continuous throughout the
      neuronal tissue. In this study, we represent bioelectric current sources in terms
      of Whitney-type elements in the finite element method (FEM) using a tetrahedral
      mesh. The aim is to study how well the Whitney elements can reproduce the
      potential and magnetic field patterns generated by a point current dipole in a
      homogeneous conducting sphere. The electric potential is solved for a unit sphere
      model with isotropic conductivity and magnetic fields are calculated for points
      located on a cap outside the sphere. The computed potential and magnetic field
      are compared with analytical solutions for a current dipole. Relative difference
      measures between the FEM and analytical solutions are less than 1%, suggesting
      that Whitney elements as bioelectric current sources are able to produce the same
      potential and magnetic field patterns as the point dipole sources.

PMID- 15972979
TI  - In vitro response of tumour cells to non-uniform irradiation.
AB  - This study examines differences in tumour cellular response using clonogenic cell
      survival between uniform and non-uniform irradiation. Cells were irradiated with
      a 6 MV x-ray intensity-modulated beam, in a single large flask (i.e.
      intercellular communication is possible) or in three small flasks (i.e.
      intercellular communication is inhibited across the dose gradient). For non-small
      cell lung cancer and melanoma cell lines, the dose response over the entire cell
      culture was significantly different between freely communicating cell cultures
      and those with inhibited communication across the dose non-uniformity.
      Communicating cells exhibited poorer survival in the low dose region of the field
      but improved survival in the high dose region. In general, the response to non
      uniform irradiation appeared to 'average out' over the entire cell culture. This
      was not seen when intercellular communication was inhibited. The results add
      strength to the body of evidence regarding bystander effects and the inter
      dependence of cellular response.

PMID- 15972980
TI  - Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell
      megacolony culture data using a non-Poissonian cell repopulation TCP model.
AB  - The effects of radiation damage, tumour repopulation and cell sublethal damage
      repair and the possibility of extracting information about the model parameters
      describing them are investigated in this work. Previously published data on two
      different cultured cell lines were analysed with the help of a tumour control
      probability (TCP) model that describes tumour cell dynamics properly. Different
      versions of a TCP model representing the cases of full or partial cell recovery
      between fractions of radiation, accompanied by repopulation or no repopulation
      were used to fit the data and were ranked according to statistical criteria. The
      data analysis shows the importance of the linear-quadratic mechanism of cell
      damage for the description of the in vitro cell dynamics. In a previous work
      where in vivo data were analysed, the employment of the single hit model of cell
      kill and cell repopulation produced the best fit, while ignoring the quadratic
      term of cell damage in the current analysis leads to poor fits. It is also
      concluded that more experiments using different fractionation regimes producing
      diverse data are needed to help model analysis and better ranking of the models.

PMID- 15972981
TI  - The three-dimensional scintillation dosimetry method: test for a 106Ru eye plaque
      applicator.
AB  - The need for fast, accurate and high resolution dosimetric quality assurance in
      radiation therapy has been outpacing the development of new and improved 2D and
      3D dosimetry techniques. This paper summarizes the efforts to create a novel and
      potentially very fast, 3D dosimetry method based on the observation of
      scintillation light from an irradiated liquid scintillator volume serving
      simultaneously as a phantom material and as a dose detector medium. The method,
      named three-dimensional scintillation dosimetry (3DSD), uses visible light images
      of the liquid scintillator volume at multiple angles and applies a tomographic
      algorithm to a series of these images to reconstruct the scintillation light
      emission density in each voxel of the volume. It is based on the hypothesis that
      with careful design and data processing, one can achieve acceptable
      proportionality between the local light emission density and the locally absorbed
      dose. The method is applied to a Ru-106 eye plaque immersed in a 16.4 cm3 liquid
      scintillator volume and the reconstructed 3D dose map is compared along selected
      profiles and planes with radiochromic film and diode measurements. The comparison
      indicates that the 3DSD method agrees, within 25% for most points or within
      approximately 2 mm distance to agreement, with the relative radiochromic film and
      diode dose distributions in a small (approximately 4.5 mm high and approximately
      12 mm diameter) volume in the unobstructed, high gradient dose region outside the
      edge of the plaque. For a comparison, the reproducibility of the radiochromic
      film results for our measurements ranges from 10 to 15% within this volume. At
      present, the 3DSD method is not accurate close to the edge of the plaque, and
      further than approximately 10 mm (<10% central axis depth dose) from the plaque
      surface. Improvement strategies, considered important to provide a more accurate
      quick check of the dose profiles in 3D for brachytherapy applicators, are
      discussed.

PMID- 15972982
TI  - Dosimetric impact of image-guided 3D conformal radiation therapy of prostate
      cancer.
AB  - The goal of this work is to quantify the impact of image-guided conformal
      radiation therapy (CRT) on the dose distribution by correcting patient setup
      uncertainty and inter-fraction tumour motion. This was a retrospective analysis
      that used five randomly selected prostate cancer patients that underwent
      approximately 15 computed tomography (CT) scans during their radiation treatment
      course. The beam arrangement from the treatment plan was imported into each
      repeat CT study and the dose distribution was recalculated for the new beam
      setups. Various setup scenarios were then compared to assess the impact of image
      guidance on radiation treatment precision. These included (1) daily alignment to
      skin markers, thus representing a conventional beam setup without image guidance,
      (2) alignment to bony anatomy for correction of daily patient setup error, thus
      representing on-line portal image guidance, and (3) alignment to the 'CTV of the
      day' for correction of inter-fraction tumour motion, thus representing on-line CT
      or ultrasound image guidance. Treatment scenarios (1) and (3) were repeated with
      a reduced CTV to PTV margin, where the former represents a treatment using small
      margins without daily image guidance. Daily realignment of the treatment beams to
      the prostate showed an average increase in minimum tumour dose of 1.5 Gy, in all
      cases where tumour 'geographic miss' without image guidance was apparent.
      However, normal tissue sparing did not improve unless the PTV margin was reduced.
      Daily realignment to the tumour combined with reducing the margin size by a
      factor of 2 resulted in an average escalation in tumour dose of 9.0 Gy for all
      five static plans. However, the prescription dose could be escalated by 13.8 Gy
      when accounting for changes in anatomy by accumulating daily doses using
      nonlinear image registration techniques. These results provide quantitative
      information on the effectiveness of image-guided radiation treatment of prostate
      cancer and demonstrate that the dosimetric impact is patient dependent.

PMID- 15972983
TI  - New irradiation geometry for microbeam radiation therapy.
AB  - Microbeam radiation therapy (MRT) has the potential to treat infantile brain
      tumours when other kinds of radiotherapy would be excessively toxic to the
      developing normal brain. MRT uses extraordinarily high doses of x-rays but
      provides unusual resistance to radioneurotoxicity, presumably from the migration
      of endothelial cells from 'valleys' into 'peaks', i.e., into directly irradiated
      microslices of tissues. We present a novel irradiation geometry which results in
      a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose
      ratio (PVDR) in the tumour area by applying an innovative cross-firing technique.
      We propose an MRT technique to orthogonally crossfire two arrays of parallel,
      nonintersecting, mutually interspersed microbeams that produces tumouricidal
      doses with small PVDRs where the arrays meet and tolerable radiation doses to
      normal tissues between the microbeams proximal and distal to the tumour in the
      paths of the arrays.

PMID- 15972984
TI  - Validation of the Monte Carlo simulator GATE for indium-111 imaging.
AB  - Monte Carlo simulations are useful for optimizing and assessing single photon
      emission computed tomography (SPECT) protocols, especially when aiming at
      measuring quantitative parameters from SPECT images. Before Monte Carlo simulated
      data can be trusted, the simulation model must be validated. The purpose of this
      work was to validate the use of GATE, a new Monte Carlo simulation platform based
      on GEANT4, for modelling indium-111 SPECT data, the quantification of which is of
      foremost importance for dosimetric studies. To that end, acquisitions of (111)In
      line sources in air and in water and of a cylindrical phantom were performed,
      together with the corresponding simulations. The simulation model included Monte
      Carlo modelling of the camera collimator and of a back-compartment accounting for
      photomultiplier tubes and associated electronics. Energy spectra, spatial
      resolution, sensitivity values, images and count profiles obtained for
      experimental and simulated data were compared. An excellent agreement was found
      between experimental and simulated energy spectra. For source-to-collimator
      distances varying from 0 to 20 cm, simulated and experimental spatial resolution
      differed by less than 2% in air, while the simulated sensitivity values were
      within 4% of the experimental values. The simulation of the cylindrical phantom
      closely reproduced the experimental data. These results suggest that GATE enables
      accurate simulation of (111)In SPECT acquisitions.

PMID- 15972985
TI  - High-resolution temperature-based optimization for hyperthermia treatment
      planning.
AB  - In regional hyperthermia, optimization techniques are valuable in order to obtain
      amplitude/phase settings for the applicators to achieve maximal tumour heating
      without toxicity to normal tissue. We implemented a temperature-based
      optimization technique and maximized tumour temperature with constraints on
      normal tissue temperature to prevent hot spots. E-field distributions are the
      primary input for the optimization method. Due to computer limitations we are
      restricted to a resolution of 1 x 1 x 1 cm3 for E-field calculations, too low for
      reliable treatment planning. A major problem is the fact that hot spots at low
      resolution (LR) do not always correspond to hot spots at high-resolution (HR),
      and vice versa. Thus, HR temperature-based optimization is necessary for adequate
      treatment planning and satisfactory results cannot be obtained with LR
      strategies. To obtain HR power density (PD) distributions from LR E-field
      calculations, a quasi-static zooming technique has been developed earlier at the
      UMC Utrecht. However, quasi-static zooming does not preserve phase information
      and therefore it does not provide the HR E-field information required for direct
      HR optimization. We combined quasi-static zooming with the optimization method to
      obtain a millimetre resolution temperature-based optimization strategy. First we
      performed a LR (1 cm) optimization and used the obtained settings to calculate
      the HR (2 mm) PD and corresponding HR temperature distribution. Next, we
      performed a HR optimization using an estimation of the new HR temperature
      distribution based on previous calculations. This estimation is based on the
      assumption that the HR and LR temperature distributions, though strongly
      different, respond in a similar way to amplitude/phase steering. To verify the
      newly obtained settings, we calculate the corresponding HR temperature
      distribution. This method was applied to several clinical situations and found to
      work very well. Deviations of this estimation method for the AMC-4 system were
      typically smaller than 0.2 degrees C in the volume of interest, which is accurate
      enough for treatment planning purposes.

PMID- 15972986
TI  - A search for optimal x-ray spectra in iodine contrast media mammography.
AB  - The aim of this work was to search for the optimal x-ray tube voltage and anode
      filter combination in digital iodine contrast media mammography. In the
      optimization, two entities were of interest: the average glandular dose, AGD, and
      the signal-to-noise ratio, SNR, for detection of diluted iodine contrast medium.
      The optimum is defined as the technique maximizing the figure of merit, SNR2/AGD.
      A Monte Carlo computer program was used which simulates the transport of photons
      from the x-ray tube through the compression plate, breast, breast support plate,
      anti-scatter grid and image detector. It computes the AGD and the SNR of an
      iodine detail inside the compressed breast. The breast thickness was varied
      between 2 and 8 cm with 10-90% glandularity. The tube voltage was varied between
      20 and 55 kV for each anode material (Rh, Mo and W) in combination with either 25
      microm Rh or 0.05-0.5 mm Cu added filtration. The x-ray spectra were calculated
      with MCNP4C (Monte Carlo N-Particle Transport Code System, version 4C). A CsI
      scintillator was used as the image detector. The results for Rh/0.3 mmCu, Mo/0.3
      mmCu and W/0.3 mmCu were similar. For all breast thicknesses, a maximum in the
      figure of merit was found at approximately 45 kV for the Rh/Cu, Mo/Cu and W/Cu
      combinations. The corresponding results for the Rh/Rh combination gave a figure
      of merit that was typically lower and more slowly varying with tube voltage. For
      a 4 cm breast at 45 kV, the SNR2/AGD was 3.5 times higher for the Rh/0.3 mmCu
      combination compared with the Rh/Rh combination. The difference is even larger
      for thicker breasts. The SNR2/AGD increases slowly with increasing Cu-filter
      thickness. We conclude that tube voltages between 41 and 55 kV and added Cu
      filtration will result in significant dose advantage in digital iodine contrast
      media mammography compared to using the Rh/Rh anode/filter combination at 25-32
      kV.

PMID- 15972987
TI  - Analytical fan-beam and cone-beam reconstruction algorithms with uniform
      attenuation correction for SPECT.
AB  - In this paper, we developed an analytical fan-beam reconstruction algorithm that
      compensates for uniform attenuation in SPECT. The new fan-beam algorithm is in
      the form of backprojection first, then filtering, and is mathematically exact.
      The algorithm is based on three components. The first one is the established
      generalized central-slice theorem, which relates the 1D Fourier transform of a
      set of arbitrary data and the 2D Fourier transform of the backprojected image.
      The second one is the fact that the backprojection of the fan-beam measurements
      is identical to the backprojection of the parallel measurements of the same
      object with the same attenuator. The third one is the stable analytical
      reconstruction algorithm for uniformly attenuated Radon data, developed by Metz
      and Pan. The fan-beam algorithm is then extended into a cone-beam reconstruction
      algorithm, where the orbit of the focal point of the cone-beam imaging geometry
      is a circle. This orbit geometry does not satisfy Tuy's condition and the
      obtained cone-beam algorithm is an approximation. In the cone-beam algorithm, the
      cone-beam data are first backprojected into the 3D image volume; then a slice-by
      slice filtering is performed. This slice-by-slice filtering procedure is
      identical to that of the fan-beam algorithm. Both the fan-beam and cone-beam
      algorithms are efficient, and computer simulations are presented. The new cone
      beam algorithm is compared with Bronnikov's cone-beam algorithm, and it is shown
      to have better performance with noisy projections.

PMID- 15972988
TI  - Contrast settling in cerebral aneurysm angiography.
AB  - During angiography, blood flow is visualized with a radiopaque contrast agent,
      which is denser than blood. In complex vasculature, such as cerebral saccular
      aneurysms, the density difference may produce an appreciable gravity effect,
      where the contrast material separates from blood and settles along the gravity
      direction. Although contrast settling has been occasionally reported before, the
      fluid mechanics behind it have not been explored. Furthermore, the severity of
      contrast settling in cerebral aneurysms varies significantly from case to case.
      Therefore, a better understanding of the physical principles behind this
      phenomenon is needed to evaluate contrast settling in clinical angiography. In
      this study, flow in two identical groups of sidewall aneurysm models with varying
      parent-vessel curvature was examined by angiography. Intravascular stents were
      deployed into one group of the models. To detect contrast settling, we used
      lateral view angiography. Time-intensity curves were analysed from the
      angiographic data, and a computational fluid dynamic analysis was conducted.
      Results showed that contrast settling was strongly related to the local flow
      dynamics. We used the Froude number, a ratio of flow inertia to gravity force, to
      characterize the significance of gravity force. An aneurysm with a larger vessel
      curvature experienced higher flow, which resulted in a larger Froude number and,
      thus, less gravitational settling. Addition of a stent reduced the aneurysmal
      flow, thereby increasing the contrast settling. We found that contrast settling
      resulted in an elevated washout tail in the time-intensity curve. However, this
      signature is not unique to contrast settling. To determine whether contrast
      settling is present, a lateral view should be obtained in addition to the
      anteroposterior (AP) view routinely used clinically so as to rule out contrast
      settling and hence to enable a valid time-intensity curve analysis of blood flow
      in the aneurysm.

PMID- 15972989
TI  - Identification of current density distribution in electrically conducting subject
      with anisotropic conductivity distribution.
AB  - Current density imaging (CDI) is able to visualize a three-dimensional current
      density distribution J inside an electrically conducting subject caused by an
      externally applied current. CDI may use a magnetic resonance imaging (MRI)
      scanner to measure the induced magnetic flux density B and compute J via the
      Ampere law [Formula: see text]. However, measuring all three components of B =
      (B(x), B(y), B(z)) has a technical difficulty due to the requirement of
      orthogonal rotations of the subject inside the MRI scanner. In this work, we
      propose a new method of reconstructing a current density image using only B(z)
      data so that we can avoid the subject rotation procedure. The method utilizes an
      auxiliary injection current to compensate the missing information of B(x) and
      B(y). The major advantage of the method is its applicability to a subject with an
      anisotropic conductivity distribution. Numerical experiments show the feasibility
      of the new technique.

PMID- 15972990
TI  - An investigation into the vector ellipticity of extremely low frequency magnetic
      fields from appliances in UK homes.
AB  - Elliptically polarized magnetic fields induce higher currents in the body
      compared with their plane polarized counterparts. This investigation examines the
      degree of vector ellipticity of extremely low frequency magnetic fields (ELF-MFs)
      in the home, with regard to the adverse health effects reportedly associated with
      ELF-MFs, for instance childhood leukaemia. Tri-axial measurements of the
      magnitude and phase of the 0-3000 Hz magnetic fields, produced by 226 domestic
      mains-fed appliances of 32 different types, were carried out in 16 homes in
      Worcestershire in the summer of 2004. Magnetic field strengths were low, with
      average (RMS) values of 0.03 +/- 0.02 microT across all residences. In contrast,
      background field ellipticities were high, on average 47 +/- 11%. Microwave and
      electric ovens produced the highest ellipticities: mean respective values of 21
      +/- 21% and 21 +/- 17% were observed 20 cm away from these appliances. There was
      a negative correlation between field strength and field polarization, which we
      attribute to the higher relative field contribution close to each individual
      (single-phase) appliance. The measurements demonstrate that domestic magnetic
      fields are extremely complex and cannot simply be characterized by traditional
      measurements such as time-weighted average or peak exposure levels. We conclude
      that ellipticity should become a relevant metric for future epidemiological
      studies of health and ELF-MF exposure.

PMID- 15972991
TI  - X-ray diffraction by a crystal in a permanent external electric field: general
      considerations.
AB  - The variations of X-ray diffraction intensities from a crystal in the presence of
      a permanent external electric field is modeled analytically using a first-order
      stationary perturbation theory. The change in a crystal, induced by an external
      electric field, is separated into two contributions. The first one is related to
      a pure polarization of an electron subsystem, while the second contribution can
      be reduced to the displacements of the rigid pseudoatoms from their equilibrium
      positions. It is shown that a change of the X-ray diffraction intensities mainly
      originates from the second contribution, while the influence of the pure
      polarization of a crystal electron subsystem is negligibly small. The quantities
      restored from an X-ray diffraction experiment in the presence of an external
      electric field were analyzed in detail in terms of a rigid pseudoatomic model of
      electron density and harmonic approximation for the atomic thermal motion.
      Explicit relationships are derived that link the properties of phonon spectra
      with E-field-induced variations of a structure factor, pseudoatomic displacements
      and piezoelectric strains. The displacements can be numerically estimated using a
      model of independent atomic motion if the Debye-Waller factors and pseudoatomic
      charges are known either from a previous single-crystal X-ray diffraction study
      or from density functional theory calculations. The above estimations can be used
      to develop an optimum strategy for a data collection that avoids the measurements
      of reflections insensitive to the electric-field-induced variations.

PMID- 15972992
TI  - Quantitative structure retrieval using scanning transmission electron microscopy.
AB  - A method is described that reconstructs the projected object potential using data
      recorded in the coherent imaging mode of a scanning transmission electron
      microscope. The technique is applicable in the presence of multiple scattering.
      It is not required that the thickness is known. Model examples exploring the
      nature of the data set required, the stability of the algorithm and the
      limitations on resolution are provided.

PMID- 15972993
TI  - Growth process of the ridge--trough faces of a twinned crystal.
AB  - For a twinned face-centered-cubic crystal, the energy barrier for two-dimensional
      nucleation on a concave trough (or a re-entrant edge) and that for a layer
      advancing across a convex ridge were calculated. The former was obtained by
      analyzing the line tension of the trough. The results show that their energy
      barriers are 39 and 50% compared to that for nucleation on a flat {111} face,
      respectively. Therefore, the layer advance across the ridge is found to be more
      difficult than the nucleation on the trough. Based on these results, the
      morphology of the growing surface is predicted and an alternative growth process
      by the twin-plane-re-entrant-edge mechanism is suggested.

PMID- 15972994
TI  - Electron-density distribution in cubic SrTiO3: a comparative gamma-ray
      diffraction study.
AB  - The electron density and atomic displacements in the perovskite SrTiO(3) have
      been studied using extensive and accurate gamma-ray diffraction data (lambda =
      0.0392 A) at room temperature. The six strongest low-order structure factors have
      been determined under extinction-free conditions. Gram-Charlier series expansion
      of the thermal parameters have revealed no evidence for anharmonicity. The
      population of the 3d subshell on Ti is found to be close to zero, in agreement
      with the observed magnetic behaviour. The electronic properties at the bond
      critical points indicate ionic Ti-O and Sr-O interactions of different strengths,
      which is corroborated by the net charges of the atomic basins [q(Sr) = 1.18 |e|,
      q(Ti) = 3.10 |e|, q(O) = -1.42 |e|]. A critical comparison is made with earlier
      experimental results from laboratory X-ray, synchrotron X-ray, electron and
      neutron diffraction studies. Agreement and discrepancies are identified and
      resolved.

PMID- 15972995
TI  - Improved data acquisition in grazing-incidence X-ray scattering experiments using
      a pixel detector.
AB  - The use of an area detector in grazing-incidence X-ray experiments lends many
      advantages in terms of both speed and reliability. Here a discussion is given of
      the procedures established using the PILATUS pixel detector developed at the
      Swiss Light Source for optimizing data acquisition and analysis of surface
      diffraction data at the Materials Science beamline, especially with regard to
      reflectivity measurements, crystal truncation and fractional order rods, and
      grazing-incidence diffraction experiments.

PMID- 15972996
TI  - On the density of homogeneous sphere packings.
AB  - For some types of sphere packing with typical one- and two-dimensional parameter
      regions, the sphere-packing density as a function of the free parameters is
      discussed. In addition, some sphere-packing types with extraordinary density
      properties are presented. Until now, it was generally assumed that sphere
      packings with minimal density are also those of highest inherent symmetry. An
      example to prove the opposite is given.

PMID- 15972997
TI  - Tetragonal sphere packings: minimal densities and subunits.
AB  - For all 382 types of homogeneous sphere packings with tetragonal symmetry, the
      minimal sphere-packing densities have been calculated. The tabulated coordinates
      allow the graphic representation of a sample packing for each type. 1- and 2
      periodic subunits of these sphere packings are listed in addition.

PMID- 15972998
TI  - Polynomial-time algorithms for the integer minimal principle for centrosymmetric
      structures.
AB  - The minimal principle for structure determination from single-crystal X-ray
      diffraction measurements has recently been formulated as an integer linear
      optimization model for the case of centrosymmetric structures. Solution of this
      model via established combinatorial branch-and-bound algorithms provides the true
      global minimum of the minimal principle while operating exclusively in reciprocal
      space. However, integer programming techniques may require an exponential number
      of iterations to exhaust the search space. In this paper, a new approach is
      developed to solve the integer minimal principle to global optimality without
      requiring the solution of an optimization problem. Instead, properties of the
      solution of the optimization problem, as observed in a large number of
      computational experiments, are exploited in order to reduce the optimization
      formulation to a system of linear equations in the number field of two elements
      (F(2)). Two specialized Gaussian elimination algorithms are then developed to
      solve this system of equations in polynomial time in the number of atoms.
      Computational results on a collection of 38 structures demonstrate that the
      proposed approach provides very fast and accurate solutions to the phase problem
      for centrosymmetric structures. This approach also provided much better
      crystallographic R values than SHELXS for all 38 structures tested.

PMID- 15972999
TI  - Refinement of the crystal structural parameters of La2/3Ca1/3MnO3 using
      quantitative convergent-beam electron diffraction.
AB  - Crystal structural parameters (seven positional parameters and four isotropic
      Debye-Waller factors) of La(2/3)Ca(1/3)MnO(3) have been refined using the
      quantitative convergent-beam electron diffraction (QCBED) method. Using intensity
      information of many higher-order Laue-zone reflections simultaneously is
      essential to refine structural parameters accurately. The effective global
      optimization algorithm was used to avoid the problems of input values and local
      minima. The fittings of the differential coefficients of one-dimensional
      experimental intensities and theoretical ones calculated by the dynamical
      diffraction theory were carried out with the normalized Euclidean distance
      criterion. Thus, all of these improve the accuracy and reliability of the
      analysis. The calculated results with the refined parameters agree with the
      experiments. The refined parameters also agree with the Rietveld refinement
      results of neutron diffraction.

PMID- 15973000
TI  - Three-beam resonant X-ray diffraction in germanium - Laue transmission cases.
AB  - Perturbation of the two-beam diffracted power owing to the influence of a third
      lattice node has been examined for various three-beam cases in a small finite
      germanium crystal in the vicinity of the K-absorption edge. Although the crystal
      was slightly imperfect, the main parts of the experimental results are very well
      described within the framework of the fundamental theory of X-ray diffraction in
      conjunction with Cromer-Liberman calculations for the resonant scattering terms.
      Beam divergence and dynamical block size are treated as adjustable parameters in
      the analysis. Observed changes in the three-beam profile asymmetry are mainly
      attributed to size and not to resonance effects associated with the triplet phase
      sum of the involved reflections. Close to the absorption edge there is however
      some evidence indicating that f' values should be reduced in magnitude compared
      to the tabulated ones.

PMID- 15973001
TI  - Outlier recognition in crystal-structure least-squares modelling by diagnostic
      techniques based on leverage analysis.
AB  - The identification of the actual outliers in a least-squares crystal-structure
      model refinement and their subsequent elimination from the data set is a non
      trivial task that has to be carried out carefully when a high level of accuracy
      of the estimates is required. One of the most suitable tools for detecting the
      influence of each data entry on the regression is the identification of ;leverage
      points'. On the other hand, the recognition of the actual statistical outliers is
      effectively possible by using some diagnostics as a function of the leverage,
      such as Cook's distance, DFFITS and FVARATIO. The evaluation of these estimators
      makes it possible to achieve a reliable identification of the outliers and the
      elimination of those that impair the least-squares fit. In this paper, a
      procedure for filtering data points based on this kind of analysis for
      crystallographic X-ray data is presented and discussed.

PMID- 15973002
TI  - Rapid calculation of RMSDs using a quaternion-based characteristic polynomial.
AB  - A common measure of conformational similarity in structural bioinformatics is the
      minimum root mean square deviation (RMSD) between the coordinates of two
      macromolecules. In many applications, the rotations relating the structures are
      not needed. Several common algorithms for calculating RMSDs require the
      computationally costly procedures of determining either the eigen decomposition
      or matrix inversion of a 3x3 or 4x4 matrix. Using a quaternion-based method, here
      a simple algorithm is developed that rapidly and stably determines RMSDs by
      circumventing the decomposition and inversion problems.

PMID- 15973004
TI  - Sphingolipids in infectious diseases.
AB  - Sphingolipids are ubiquitous constituents of membrane lipids in eukaryotes.
      Sphingolipid metabolites modulate various cellular events including
      proliferation, differentiation, and apoptosis. In addition, sphingolipids, along
      with cholesterol, form detergent-resistant membrane microdomains, so called
      'lipid-rafts', which are implicated in signal transduction and membrane
      trafficking. Sphingolipids are also relevant to infectious diseases. Various
      types of pathogens exploit the sphingolipids of host cells as membrane receptors.
      Sphingolipid metabolites regulate pathogen infection and host defense: for
      instance, a specific glycosphingolipid acts as an endogenous ligand for
      activation of natural killer T cells. Lipid-rafts of host cells serve as
      platforms also for infection signaling and entry of intracellular parasites.
      Moreover, some post-infectious autoimmune diseases result from production of
      antibodies cross-reacting with mammalian sphingolipids. Differences in the
      pathways of sphingolipid metabolism between mammals and non-mammals are good
      clues for rational development of new anti-infectious disease drugs. This review
      summarizes recent advances in sphingolipid biology related to infectious
      diseases.

PMID- 15973003
TI  - The interaction of HIV-1 with the host factors.
AB  - Human immunodeficiency virus type 1 (HIV-1) is a causative agent of acquired
      immunodeficiency syndrome (AIDS) in humans. In the last decade, the functions of
      HIV-1-encoded genes have been intensively studied. These studies have contributed
      to the development of the effective anti-AIDS drugs directing against the HIV-1
      encoded enzymes, namely reverse transcriptase and protease. However, even the
      combination of these drugs is not sufficient enough to stop the progression of
      AIDS partly due to the emergence of drug-resistant HIV-1 mutants as well as the
      severe side effects. Understanding the molecular mechanisms by which cellular
      factors support the efficient replication of HIV-1 should contribute to develop
      means to control the progression of AIDS. This field is now expanding rapidly.
      Here we review the host factors involved in the replication of HIV-1 and
      highlight some findings that have a substantial impact on the retroviral
      research.

PMID- 15973005
TI  - Spontaneous resolution of hemophagocytic syndrome and disseminated intravascular
      coagulation associated with parvovirus b19 infection in a previously healthy
      child.
AB  - A 10-year-old male with a brain abscess developed pancytopenia, liver
      dysfunction, disseminated intravascular coagulation (DIC) and decrease of
      immunoglobulin A (IgA) level during postoperative antibiotic and anticonvulsant
      therapy. A bone marrow examination revealed hemophagocytosis. Real-time PCR
      revealed parvovirus B19 infection. The hemophagocytic syndrome resolved without
      specific treatment. To our knowledge, this is the first report of a spontaneous
      resolution of parvovirus B19-associated hemophagocytic syndrome and DIC.

PMID- 15973006
TI  - Which patients are able to adhere to tuberculosis treatment? A study in a rural
      area in the northwest part of Turkey.
AB  - The purpose of this study was to investigate various factors, including
      demographical, socioeconomical, clinical and radiological features, of adherent
      and nonadherent patients with tuberculosis (TB) who were admitted to a university
      hospital between 1998 and 2003. One hundred and one patients (65.5%) and 53
      patients (34.5%) met the criteria of adherence and nonadherence, respectively. A
      higher rate of adherence was observed among females than males (79.2 versus
      58.4%, respectively, P = 0.012). Older patients were more nonadherent (P =
      0.008). The adherence rate in non-smokers was significantly higher than that of
      smokers (81.4 and 52.4%, respectively, P = 0.000). Patients who underwent "family
      screening" were more adherent (75.7%) than those (39.5%) who did not (P = 0.000).
      Patients with pleurisy had higher adherence rates (81.3%), followed by patients
      with pulmonary TB (65.0%), while patients with extrarespiratory TB had the lowest
      adherence rates (45.5%) (P = 0.024). The presence of cough was significantly
      associated with adherence (P = 0.049). A significantly higher adherence rate was
      observed in patients without hemoptysis (P = 0001). A univariate logistic
      regression confirmed that age, smoking, family screening, type of TB, cough and
      hemoptysis had significant independent effects on the adherence to treatment of
      TB. High-risk patients may be identified and interventions tailored to promote
      adherence before concluding that the patient is willfully refusing treatment.

PMID- 15973007
TI  - Increasing antimicrobial resistance in Escherichia coli isolates from community
      acquired urinary tract infections during 1998-2003 in Manisa, Turkey.
AB  - Urinary tract infections are among the most common infections with an increasing
      resistance to antimicrobials. The aim of this study was to determine the change
      in antimicrobial susceptibility of Escherichia coli isolates from patients with
      community-acquired urinary tract infection (UTI) for the years 1998 through 2003
      and to suggest that the current empirical antibiotic therapy used for these
      patients is inappropriate. During the study period, 7,335 community urine samples
      of which 1,203 (16.4%) grew bacterial isolates were analyzed. Among the total of
      1,203 isolates, 880 (73.2%) were E. coli. The range of resistance of E. coli to
      ampicillin was 47.8 to 64.6% and that to trimethoprim-sulfamethoxazole was 37.1
      to 44.6% during the study period. The susceptibility pattern of E. coli to
      nitrofurantoin and cefuroxime did not vary significantly over the 6-year period.
      There was a significant increase in the susceptibility of E. coli to
      ciprofloxacin (11.3 - 26.7%), amoxicillin-clavulanate (18.4 - 29.2%) and
      gentamicin (7.0 - 25.6%) (P < 0.05). Empirical initial treatment with ampicillin
      and trimethoprim-sulfamethoxazole was thus inadequate in approximately half of
      UTI cases in our region.

PMID- 15973008
TI  - Molecular characterization of TEM- and SHV-derived extended-spectrum beta
      lactamases in hospital-based Enterobacteriaceae in Turkey.
AB  - TEM- and SHV-derived extended-spectrum beta-lactamases (ESBLs) producing
      Enterobacteriaceae have been reported from throughout the world, but there has
      been limited data for the molecular characterization of these enzymes in Turkey.
      The aim of this study was to investigate and to type the TEM- and SHV-derived
      ESBLs in 63 ESBL-producing clinical isolates of Enterobacteriaceae, and it
      included further analysis; transfer experiments, isoelectric focusing, PCR, PCR
      restriction fragment length polymorphism, and DNA sequencing. According to PCR
      results the transconjugant strains included 52.7% TEM, 74.3% SHV, and 32.4% of
      both the TEM and SHV genes. Using PCR/NheI restriction analysis, 45 of the 46
      ESBL detected in transconjugants were determined to be SHV-derived. DNA
      sequencing was performed for the identification of TEM- and SHV-derived ESBLs for
      18 selected transconjugants. SHV-2, SHV-5, and SHV-12 were detected in five,
      seven, and five samples, respectively. This is the first description of SHV-12 in
      Turkey.

PMID- 15973009
TI  - Clinical characteristics of adult Escherichia coli meningitis.
AB  - The clinical characteristics and therapeutic outcomes of adult meningitis due to
      Escherichia coli alone have not been examined adequately. In this study, we
      analyzed the clinical and laboratory data of 15 adult patients with monomicrobial
      E. coli meningitis. The 15 patients, collected over a period of 18 years (January
      1986-December 2003), included 7 men and 8 women, aged 45-77 years. They accounted
      for 5% (15/306) of our adult bacterial meningitis with single pathogen infection.
      This study also revealed that a post-neurosurgical state is the most important
      factor predisposing adult patients to develop E. coli meningitis. In this study,
      all of the tested E. coli strains showed their susceptibility to imipenem and/or
      meropenem, however, E. coli strains that are not susceptible to third-generation
      cephalosporin have emerged since 2001. As to the therapeutic results of these 15
      cases, all 4 patients without appropriate antibiotic treatment died and the other
      11 patients with appropriate antibiotic treatment showed a mortality rate of 27%.
      The emergence of third-generation cephalosporin non-susceptible E. coli strains
      in adult bacterial meningitis, as shown in this study, has caused a therapeutic
      challenge in choosing initial empirical antibiotics for treating adult patients
      with post-neurosurgical meningitis. Our results emphasize that the timely use of
      appropriate antibiotics is essential for the management of this potentially fatal
      central nervous system infection. However, it should be noted that the number of
      cases examined in this study is too small to reach a therapeutic conclusion
      regarding adult E. coli meningitis, and further large-scale studies will be
      needed for this purpose.

PMID- 15973010
TI  - Value of surveillance blood cultures in neutropenic patients--a pilot study.
AB  - In this prospective pilot study we evaluated the efficacy of blood cultures (BC)
      in detecting bacteremia and fungemia prior to the occurrence of infectious signs.
      Between February 2003 and July 2003, BC were performed twice weekly in
      neutropenic hematological patients using blood drawn from central venous
      catheters. Microbial growth prior to the onset of infectious symptoms was
      detected in 3 of 45 neutropenic episodes in 39 patients and led to modifications
      in patient management. These results suggest that further prospective studies are
      warranted to determine the clinical usefulness of surveillance with BC in
      neutropenic patients.

PMID- 15973011
TI  - Antimicrobial susceptibility pattern of blood isolates from a teaching hospital
      in north India.
AB  - Bloodstream infections are associated with significant patient morbidity and
      mortality worldwide. In this study, we examined antimicrobial susceptibility
      patterns by reviewing the data on 5,704 blood samples that were collected from
      patients with fever/sepsis admitted to Government Medical College and Hospital,
      Chandigarh, India, over a period of 1 year from August 2003 to July 2004. Among
      the 567 qualifying samples, Pseudomonas aeruginosa (19.75%), Escherichia coli
      (15.17%), Klebsiella pneumoniae (14.99%), and Salmonella enterica serovar Typhi
      (12.87%) were the most frequently isolated Gram-negative bacteria other than
      Citrobacter, Acinetobacter, Proteus, and Enterobacter spp. collectively
      accounting for 80.96% of the isolates. Staphylococus aureus (13.86%) and
      Enterococcus feacalis (2.35%) were most frequently isolated Gram-positive
      bacteria other than other Streptococcus and Staphylococcus spp. collectively
      accounting for 18% of the isolates. Among the antibiotics used for susceptibility
      testing of Gram-negative isolates, amikacin showed higher activity (76.61%)
      against Enterobacteriaceae and ciprofloxacin (65.17%) against non-fermenters.
      However, cefoperazone + sulbactum showed the highest activity (82.66%) among all
      Gram-negative isolates. For Gram-positive isolates, vancomycin (100%),
      ciprofloxacin (89.74%) showed the highest activity against Staphylococcus spp.
      Combinations of antibiotics are often prescribed as emperic therapy for
      bacteremia, especially for Gram-negative pathogens. Hence the antibiotic
      susceptibility patterns of blood isolates reported here may be a useful guide for
      physicians initiating emperic therapy with antibiotics.

PMID- 15973012
TI  - Spinal epidural abscess caused by group B Streptococcus in a diabetic woman
      presenting with febrile low back pain.
AB  - Because spinal epidural abscess is usually ignored in the preliminary
      differential diagnosis of low back pain, appropriate treatment may be delayed.
      Adult spinal epidural abscess is sparsely caused by the pathogen known as group B
      Streptococcus. In this paper, we report the case of a diabetic woman with lumbar
      epidural abscess and vertebral osteomyelitis caused by group B Streptococcus.
      Owing to the main manifestations of fever, pyuria and low back pain, which
      originally led us to suspect acute pyelonephritis, empirical antibiotics were
      applied. When the symptoms and signs persisted, other focal infections were
      considered. Magnetic resonance imaging led to the correct diagnosis. Group B
      Streptococcus was isolated from the blood but not from the abscess itself,
      probably due to the prior antibiotic treatment. The patient recovered well after
      surgical debridement followed by prolonged intravenous penicillin therapy.
      Therefore, despite the potential for fatality, our results suggest that epidural
      abscess can be successfully treated with surgery and antibiotic therapy provided
      that it is detected early enough.

PMID- 15973013
TI  - Evaluation of pulsed-field gel electrophoresis analysis performed at selected
      prefectural institutes of public health for use in PulseNet Japan.
AB  - In order to evaluate reliability of pulsed-field gel electrophoresis (PFGE)
      analysis performed at different prefectural public health institutes (PHIs) for
      use in the PulseNet Japan surveillance system to detect enterohemorrhagic
      Escherichia coli O157, we compared the results of PFGE-typing of 14 selected
      strains of O157 performed at 8 selected PHIs to evaluate the reliability of
      different experimental protocols used in these PHIs. PFGE was performed for 14
      strains for which there were 14 PFGE types in 3 PHIs, and 13 PFGE types in 5 PHIs
      by using their own protocols and/or those of the National Institute of Infectious
      Diseases (NIID). PFGE fingerprints from 5 out of the 8 PHIs were successfully
      genotyped for all of the 14 strains. A PFGE fingerprint from one PHI was
      successfully genotyped when the NIID pulsing protocol was used, but was not
      genotyped when the PHI's own protocols were used. PFGE fingerprints from 2 PHIs
      failed to be genotyped for one each of the strains. The cause of this genotyping
      failure was considered to be inappropriate PFGE pulsing protocols or inadequate
      digestion of chromosomal DNA. These results suggest that PFGE protocols should be
      standardized for the establishment of PulseNet Japan.

PMID- 15973014
TI  - Molecular evidence of the dispersal of Lyme disease Borrelia from the Asian
      Continent to Japan via migratory birds.
AB  - Based on specific sequencing, we found that a Borrelia garinii strain from a
      rodent in Fukui Prefecture, Japan was highly similar to the unique Borrelia
      strains (pattern R'/R) isolated in northeastern China and Korea, and to strains
      from ticks feeding on migratory birds in Fukui Prefecture. These findings
      indicate that the Borrelia with this unique pattern may be locally naturalized to
      the epizootic transmission cycle in Japan, and that Borrelia is dispersed from
      the Asian Continent to Japan via migratory birds.

PMID- 15973015
TI  - Mycobacterium branderi isolated from pus of a right pulmonary cavitary lesion.

PMID- 15973016
TI  - An outbreak of food poisoning caused by an enteropathogeic Escherichia coli
      O115:H19 in Miyagi Prefecture.

PMID- 15973017
TI  - Outbreak of enterohemorrhagic Escherichia coli O121 among school children exposed
      to cattle in a ranch for public education on dairy farming.

PMID- 15973018
TI  - A fatal food intoxication case due to Salmonella Haifa.

PMID- 15973019
TI  - Serodiagnosis of childhood tuberculosis by ELISA.
AB  - OBJECTIVE: Diagnosis of childhood tuberculosis remains an enigma despite many
      recent technological developments. The present study has been taken up with the
      aim to assess the diagnostic potential of mycobacterium tuberculosis excretory
      secretory ES-31 antigen and affinity purified anti ES-31 antibodies in the
      serodiagnosis of different spectrum of childhood tuberculosis. METHODS:
      Mycobacterium tuberculosis H37Ra excretory-secretory antigen (ES-31) and affinity
      purified goat anti ES-31 antibodies were used in stick penicillinase ELISA for
      IgG antibody detection and stick Sandwich penicillinase ELISA for detection of
      circulating free and immune complexed antigen in the sera of 230 children.
      RESULTS: Analysis of tubercular antibody, circulating free and immune complexed
      antigen (CIC-Ag) was done in both pulmonary and extrapulmonary form of childhood
      tuberculosis and overall sensitivity of 81.4% with a specificity of 93% was
      achieved for detection of antitubercular IgG antibodies. Of the five cases of
      pulmonary tuberculosis showing absence of IgG antibody, 3 showed the presence of
      CIC-Ag and one was found positive for both free and CIC-Ag. Similarly out of 8
      cases of extrapulmonary childhood tuberculosis missed by IgG detection 5 were
      found to be positive for CIC-Ag and 1 showed the positive reaction for both free
      and immune complexed antigens. CONCLUSION: IgG antibody to excretory-secretory
      antigen ES-31 is found to be having good specificity with acceptable sensitivity
      in detecting different forms of childhood tuberculosis. Further detection of
      circulating free and/or immunecomplexed antigen can be used as an adjunct tool in
      the diagnosis of childhood tuberculosis.

PMID- 15973020
TI  - Duchenne muscular dystrophy: prevalence and patterns of cardiac involvement.
AB  - In about 10% cases of Duchenne muscular dystrophy (DMD), death is due to cardiac
      dysfunction. The recognition of cardiomyopathy in DMD is thus important.
      OBJECTIVE: To assess cardiac involvement in DMD patients by clinical,
      radiographic, electrocardiographic (ECG) and echocardiographic monitoring and
      correlate clinical parameters, CPK levels, presence of gene deletion and steroid
      therapy with cardiac involvement. METHODS: Thirty patients beyond 6 years age,
      with DMD in advanced stage disease/non-ambulatory were recalled. A detailed
      clinical evaluation, CPK levels, gene deletion studies were carried out. Cardiac
      investigations included Chest X-ray, 12 lead ECG and echocardiography. RESULTS:
      Nineteen patients were non-ambulatory at the time of enrollment. Symptoms or
      signs suggestive of cardiac dysfunction were seen in only 10%. Gene deletion was
      identified in 70.3%. Around one-third patients had cardiomegaly. ECG
      abnormalities were present in 93.3% patients and commonest abnormality was R > 4
      mm in V1. Ejection fraction (EF) < 55% was observed in 64.2% and EF < 50% in
      17.8%. CONCLUSION: Cardiomyopathy of DMD is characterized by lack of symptoms and
      few physical signs. Presence of subtle changes like sinus tachycardia may suggest
      early cardiac involvement. Thus echocardiography is required for evaluation of
      cardiac dysfunction. Presence of gene deletion was associated with higher CT
      ratio. Older children have been found to have higher heart rates. No other
      significant correlation with clinical parameters, CPK levels, genotype and
      steroid therapy was observed. Early detection possibly leads to appropriate
      treatment thus reducing the morbidity.

PMID- 15973021
TI  - Socio-demographic co-relates of psychiatric disorders.
AB  - OBJECTIVE: To find out the magnitude of probable psychopathology in children and
      study association of psychopathology with demographic, developmental and social
      factors. METHODS: Childhood Psychopathology Measurement Schedule (CPMS) was used
      to measure the magnitude of probable psychopathology in 620 children from an
      urban slum of Miraj (Maharashtra). A second schedule recorded demographic,
      developmental and social factors. RESULTS: CPMS score > 10 was observed in 102
      children (16.5%). It was significantly higher in children aged 7-10 years, in
      males, belonging to lower socioeconomic status, large families, being first born,
      having low birth weight (LBW); body mass index (BMI) less than 18.5. Low maternal
      education and alcohol abuse in father also had significant association with CPMS
      score > 10. CONCLUSION: Findings suggest a need to educate the community about
      psychological implications of LBW, large family size and overcrowding in
      children. Improving maternal education and controlling alcoholism could help in
      reducing childhood psychopathology.

PMID- 15973022
TI  - Benign acute childhood myositis.
AB  - OBJECTIVE: To describe the clinical and laboratory features of benign acute
      childhood myositis. METHODS: 40 children of BACM were seen during October 2001 to
      February 2002, 22 (52%) were male with mean age of 5.3 years. Duration of illness
      was 3.97 days. Preceding symptoms included fever, leg pain, vomiting and
      inability to walk. A provisional diagnosis of viral myositis was made in 26
      (66%). Guillian Barre Syndrome was the most common referral diagnosis. RESULTS:
      11 (27.5%) children had leucopenia with lymphocytic response and 16 (40%) had
      thrombocytopenia. CRP was negative in 32 (80%). CPK was markedly elevated (more
      than 1000 IU/l) in 18 (45%) and more than 500 IU/l in 11 (27.5%) remaining
      between 200 to 500 IU/l. Associated features were hepatitis (elevated SGOT &
      SGPT) in 28 (70%) and shock in 5 (12.5%). Serological test were indicative of
      dengue virus (Elisa PAN BIO) in 20 (50%) of which 8 (25%) were primary dengue and
      12 (30%) were secondary dengue. The outcome of therapy mainly supportive were
      excellent. CONCLUSION: Benign acute myositis occurs often in association with
      viral infection. In the present study, Dengue virus was positive in 20 (50%)
      children. Benign acute myositis can be differentiated from more serious causes of
      walking difficulty by presence of calf and thigh muscle tenderness on stretching,
      normal power and deep tendon reflex and elevated CPK.

PMID- 15973024
TI  - Imaging of congenital anomalies of the gastrointestinal tract.
AB  - The radiological imaging plays a vital role in the evaluation of patients with
      congenital anomalies of the gastrointestinal tract. The evaluation of these
      patients, most of which present early after birth, frequently requires the use of
      various imaging modalities for making the correct diagnosis and planning surgical
      correction. This article reviews the common congenital anomalies of the
      gastrointestinal tract including obstructive lesions, anomalies of rotation and
      fixation, anorectal anomalies, and intestinal duplications. The plain radiograph
      is often diagnostic in neonates with complete gastric of upper intestinal
      obstruction and further radiologic evaluation may be unnecessary. An upper
      gastrointestinal series should be performed in all patients with incomplete
      intestinal obstruction. Sonography is useful in the evaluation of many congenital
      anomalies affecting pediatric gastrointestinal tract especially hypertrophic
      pyloric stenosis, enteric duplication cysts, midgut malrotation, meconium ileus
      and meconium peritonitis. Moreover, CT and MRI has assumed a greater importance
      as these provide excellent anatomic details which may be necessary for correct
      diagnosis as well as treatment planning. This is particularly true in evaluation
      of congenital anomalies such as esophageal/enteric duplications, vascular rings
      and anorectal anomalies. It is important to be familiar with the role nad
      usefulness of the various imaging modalities so that these can be used
      judiciously to avoid unnecessary radiation exposure while minimizing the patient
      discomfort.

PMID- 15973025
TI  - Neonatal surgical jaundice revisited.
AB  - Neonatal hyperbilirubinemia is a common problem in newborn nurseries and manifest
      clinically as jaundice. Nearly 25-50% of all newborns and a much higher
      percentage of premature babies develop hyperbilirubinemia. This is mostly
      physiological, but a small percentage of these babies have pathological jaundice,
      requiring detailed investigations and management. It is also absolutely essential
      to consider a possibility of extra-hepatic biliary atresia early, during
      management of a case of neonatal direct hyperbilirubinemia as early surgical
      intervention results in a better outcome in EHBA. This article aims to describe
      the diagnostic approach to neonatal hyperbilirubinemia with special emphasis on
      conditions requiring surgical intervention also it throws light on present status
      of EHBA in Indian circumstances.

PMID- 15973026
TI  - Respiratory distress in neonates.
AB  - Respiratory distress due to either medical or surgical causes occurs commonly in
      neonates. It is the most common cause of admission to a neonatal surgical
      intensive care facility in a tertiary care hospital. The distress can be caused
      by a variety of clinical conditions; common conditions treated in medical
      intensive care units are transient tachypnea of the new born, respiratory
      distress syndrome, pulmonary air leak and pneumothorax. In surgical causes of
      respiratory distress in neonates the underlying mechanisms include airway
      obstruction, pulmonary collapse or displacement and parenchymal disease or
      insufficiency; the common causes are congenital diaphragmatic hernia, congenital
      cystic adenomatoid malformation, congenital lobar emphysema and esophageal
      atresia with or without tracheo-esophageal fistula. Obstructive lesions of the
      new born airway include choanal atresia, macroglossis, Pierre-Robin syndrome,
      lymphangioma, teratoma or other mediastinal masses, cysts, subglottic stenosis
      and laryngo tracheomalacia. Imaging plays a very major role in the pre-operative
      diagnosis of these conditions and proper pre-operative resuscitation helps in
      improving the results of surgery dramatically.

PMID- 15973027
TI  - The undescended testis.
AB  - Testicular development is determined by the influence of the SRY gene on the Y
      chromosome of the fetus. This influences the germ cells to produce testosterone
      and Mullerian inhibiting substance which control descent of the testis.
      Maldescent of the testis occurs in 0.8% of boys. Current best advice is to
      perform orchidopexy before the age of two years, therefore a programme for
      examination by skilled healthcare workers should be established in the first year
      of life. Indications for surgery include a possible beneficial effect on
      fertility, malignant potential particularly if intra-abdominal, torsion or trauma
      and social considerations. Hormonal treatment in the first three months of life
      is recommended by some. Laparoscopy is the optimum method for evaluating and
      managing the intra-abdominal testis.

PMID- 15973028
TI  - Current status of fetal surgery.
AB  - The allure of fetal surgery is the possibility of interrupting in utero
      progression of an otherwise treatable condition. In spite of advances in prenatal
      diagnosis and refinements in surgical techniques, this field has not yet got off
      the ground because the risks to the mother and fetus, during and after the
      procedure far outweigh the benefits, and the infrastructure required to support
      such activity is prohibitively expensive. The various surgical conditions in
      which fetal surgery has been attempted and the present status of this specialty
      are discussed.

PMID- 15973029
TI  - Refractory isosporiasis.
AB  - The authors describe a case of severe debilitating diarrhea due to isosporiasis
      in a two year old child, a known case of systemic vasculitis receiving prolonged
      corticosteroids therapy, an association rarely reported previously. It was
      refractory to treatment with dihydrofolate reductase inhibitor combined with
      sulfonamide such as cotrimoxazole to which isosporiasis usually responds well and
      is being described here for clinical interest and uniqueness of its presentation
      and laboratory findings.

PMID- 15973030
TI  - Bruck syndrome.
AB  - The combination of arthrogryposis multiplex congenita and osteogenesis imperfecta
      is extremely rare. This combination is named Bruck syndrome. A 34 week male baby
      weighing 1.7 kg at birth was noted to have multiple flexion contractures and
      pterygia at elbows, wrists and knees, in addition to right foot talipes
      equinovarus deformity. Postnatally the child developed multiple swellings
      involving both the upper and lower limbs. A plain radiograph revealed the
      presence of fractures involving the long bones of the upper and lower limbs. A
      diagnosis of osteogenesis imperfecta with arthrogryposis multiplex congenita was
      made, and the patient was labeled as a case of Bruck Syndrome. The aim of this
      report is to make the readers aware regarding this rare entity and to
      specifically look for presence of features suggestive of osteogenesis imperfecta
      when encountered with a neonate born with arthrogryposis multiplex congenita.

PMID- 15973031
TI  - Congenital stridor due to bilateral vocal cord palsy.
AB  - Congenital stridor is one of the rare presentations of respiratory distress at
      birth. The commonest cause of congenital stridor is laryngomalacia, which
      accounts for 60% of the causes. The other common causes are congenital subglottic
      stenosis and vocal cord palsy (VCP). VCP is usually unilateral and most often
      linked with birth trauma, and is temporary. Bilateral palsy can be associated
      with other congenital anomalies. The current report describes a case of
      congenital bilateral VCP, not related to birth trauma and severe enough to
      require tracheostomy.

PMID- 15973032
TI  - Familial spontaneous pneumothorax in neonates.
AB  - Spontaneous pneumothorax is a recognised cause of respiratory distress in the
      neonatal period. Spontaneous pneumothorax occurring during the neonatal period in
      siblings within a family is rare. We report a case of spontaneous pneumothorax
      occurring in two siblings in the neonatal period.

PMID- 15973034
TI  - What is the true incidence of measles?

PMID- 15973035
TI  - Gangrene of an occipital encephalocele.

PMID- 15973036
TI  - Production of recombinant protein using the HeLa S3-vaccinia virus expression
      system: bioreactor perfusion and effects of post-infection temperature.
AB  - Adaptation of the vaccinia virus expression system to HeLa S3 suspension
      bioreactor culture for the production of recombinant protein was conducted.
      Evaluation of hollow fiber perfusion of suspension culture demonstrated its
      potential for increased cell density prior to infection. The hollow fiber was
      also used for medium manipulations prior to infection. Two process parameters,
      multiplicity of infection (MOI) and temperature during the protein production
      phase, were evaluated to determine their effect on expression of the reporter
      protein, enhanced green fluorescent protein (EGFP). An MOI of 1.0 was sufficient
      for infection and led to the highest level of intracellular EGFP expression.
      Reducing the temperature to 34 degrees C during the protein production phase
      increased production of the protein two-fold compared to 37 degrees C in spinner
      flask culture. Scaling up the process to a 1.5-liter bioreactor with hollow fiber
      perfusion led to an overall production level of 9.9 microg EGFP/10(6) infected
      cells, or 27 mg EGFP per liter.

PMID- 15973037
TI  - Purification and characterization of a thermostable raw starch digesting amylase
      from a Streptomyces sp. isolated in a milling factory.
AB  - A raw starch utilizing microbe was isolated from mud in a milling factory. The
      16S ribosomal DNA (rDNA) sequencing and morphological properties of the strain
      indicated that it belongs to the genus Streptomyces. A strongly raw starch
      digesting amylase was purified from the culture supernatant of the strain by
      chromatographic procedures. The specific activity of the enzyme was 11.7 U/mg,
      molecular mass 47 kDa, optimum pH 6.0, and optimum temperature 50 to 60 degrees
      C. The enzyme showed sufficient activity even at 70 degrees C. It was activated
      by calcium, cobaltous, and magnesium ions, and inhibited by copper, nickel, zinc,
      and ferrous ions. It formed maltose mainly from raw and gelatinized starch, and
      glycogen. No products were formed from glucose, maltose, maltotriose, pullulan,
      or cyclodextrins (CDs). The enzyme digested raw wheat, rice, and waxy rice starch
      rapidly, and raw corn, waxy corn, sweet potato, tapioca, and potato starch
      normally.

PMID- 15973038
TI  - IEC-6 intestinal cell death induced by bovine milk alpha-lactalbumin.
AB  - Potent inhibition of cell proliferation was found for commercial preparations of
      bovine alpha-lactalbumin on cultured intestinal cell line IEC-6 albeit lot
      dependent. The inhibition was irreversible and a single exposure to the culture
      medium containing alpha-lactalbumin of an active lot for a period as short as 30
      min was enough to provoke cell death, possibly through apoptosis. The oligomer
      fraction from size exclusion chromatography was significantly robust, while the
      monomer fraction remained totally inert, in inducing cell death. Incubation at 37
      degrees C for 5 d with 30% trifluoroethanol in acetate, pH 5.5, in a slowly
      rotating test tube rendered the monomer fraction cytotoxic. Again, the resulting
      inhibitory activity was found in the oligomer fraction from size exclusion
      chromatography, with emergence of subtle peaks at 22- and 30-kDa. Furthermore,
      the occurrence of SDS-stable 30-kDa as well as 20-kDa bands on electrophoresis
      was a common feature for alpha-lactalbumin with the activity inducing cell death.
      Thus, a certain dimeric state can be implicated in the cytotoxicity of bovine
      alpha-lactalbumin.

PMID- 15973039
TI  - Copper-dependent production of a Pycnoporus coccineus extracellular laccase in
      Aspergillus oryzae and Saccharomyces cerevisiae.
AB  - Laccase is a multicopper-containing enzyme that catalyzes the oxidation of
      phenolic compounds. lcc1 cDNA coding for a secretory laccase of Pycnoporus
      coccineus was expressed under the maltose inducible amyB promoter in Aspergillus
      oryzae and under the galactose inducible GAL10 promoter in Saccharomyces
      cerevisiae. Laccase activities, which were undetectable in the absence of copper,
      were observed by increasing copper concentrations in the media for both systems.
      The amounts of secreted laccase protein but not lcc1 mRNA increased in proportion
      to copper concentrations in A. oryzae. The extracellular activities of native A.
      oryzae amylase and recombinant RNase-T1 expressed from the same amyB promoter in
      A. oryzae were constant regardless of copper concentrations. Our results indicate
      that a high copper concentration is required for the production of active laccase
      in heterologous hosts and that the copper is required for a post-transcriptional
      process.

PMID- 15973040
TI  - Representation of individual gene expression in completely pooled mRNA samples.
AB  - Designing microarray experiments, scientists are often confronted with the
      question of pooling due to financial constraints, but discussion of the validity
      of pooling tends toward a sub-pooling recommendation. Since complete pooling
      protocols can be considered part of sub-pooling designs, gene expression data
      from three complete pooling experiments were analyzed. Data from complete pooled
      versus individual mRNA samples of rat brain tissue were compared to answer the
      question whether the pooled sample represents individual samples in small-sized
      experiments. Our analytic approach provided clear results concerning the
      Affymetrix MAS 5.0 signal and detection call parameters. Despite a strong
      similarity of arrays within experimental groups, the individual signals were
      evidently not appropriately represented in the pooled sample, with slightly more
      than half of all the genes considered. Our analysis reveals problems in cases of
      small complete pooling designs with less than six subjects pooled.

PMID- 15973041
TI  - Effect of lactational exposure to tributyltin chloride on innate immunodefenses
      in the F1 generation in mice.
AB  - We examined the effect of lactational exposure to tributyltin on innate
      immunodefenses in the F1 generation using in vivo and in vitro experiments.
      Pregnant C57BL/6 mice were given drinking water containing 0, 15, or 50 microg/ml
      of tributyltin chloride (TBTCl) from parturition to weaning. At weaning time,
      offspring were inoculated with Escherichia coli K-12, and bacterial clearances
      from the peritoneal cavity and spleen were examined. In vivo infection
      experiments indicated that bacterial clearance was significantly depressed in
      offspring breast-fed by dams exposed to 15 microg/ml of TBTCl (15 ppm F1), but
      not in offspring by dams exposed to 50 microg/ml of TBTCl (50 ppm F1). In vitro
      functional assays revealed that the killing activity of neutrophils decreased
      significantly in 15 ppm F1, but not in 50 ppm F1. We suggest that lactational
      exposure to TBT impairs innate immunodefenses in the F1 generation against non
      pathogenic bacterial infection.

PMID- 15973042
TI  - Regulation of substrate specificity of plant alpha-mannosidase by cobalt ion: in
      vitro hydrolysis of high-mannose type N-glycans by Co2+-activated Ginkgo alpha
      mannosidase.
AB  - In our previous study (Woo, K. K., et al., Biosci. Biotechnol. Biochem., 68, 2547
      2556 (2004), we purified an alpha-mannosidase from Ginkgo biloba seeds; it was
      activated by cobalt ions and highly active towards high-mannose type free N
      glycans occurring in plant cells. In the present study, we have found that the
      substrate specificity of Ginkgo alpha-mannosidase is significantly regulated by
      cobalt ions. When pyridylamino derivative of Man9GlcNAc2 (M9A) was incubated with
      Ginkgo alpha-mannosidase in the absence of cobalt ions, Man5GlcNAc2-PA (M5A)
      having no alpha1-2 mannosyl residue was obtained as a major product. On the other
      hand, when Man9GlcNAc2-PA was incubated with alpha-mannosidase in the presence of
      Co2+ (1 mM), Man3-1GlcNAc2-PA were obtained as major products releasing alpha1
      3/6 mannosyl residues in addition to alpha1-2 mannosyl residues. The structures
      of the products (Man8-5GlcNAc2-PA) derived from M9A by enzyme digestion in the
      absence of cobalt ions were the same as those in the presence of cobalt ions.
      These results clearly suggest that the trimming pathway from M9A to M5A is not
      affected by the addition of cobalt ions, but that hydrolytic activity towards
      alpha1-3/6 mannosyl linkages is stimulated by Co2+. Structural analysis of the
      products also showed clearly that Ginkgo alpha-mannosidase can produce truncated
      high-mannose type N-glycans, found in developing or growing plant cells,
      suggesting that alpha-mannosidase might be involved in the degradation of high
      mannose type free N-glycans.

PMID- 15973043
TI  - Molecular properties of membrane-bound FAD-containing D-sorbitol dehydrogenase
      from thermotolerant Gluconobacter frateurii isolated from Thailand.
AB  - There are two types of membrane-bound D-sorbitol dehydrogenase (SLDH) reported:
      PQQ-SLDH, having pyrroloquinoline quinone (PQQ), and FAD-SLDH, containing FAD and
      heme c as the prosthetic groups. FAD-SLDH was purified and characterized from the
      PQQ-SLDH mutant strain of a thermotolerant Gluconobacter frateurii, having
      molecular mass of 61.5 kDa, 52 kDa, and 22 kDa. The enzyme properties were quite
      similar to those of the enzyme from mesophilic G. oxydans IFO 3254. This enzyme
      was shown to be inducible by D-sorbitol, but not PQQ-SLDH. The oxidation product
      of FAD-SLDH from D-sorbitol was identified as L-sorbose. The cloned gene of FAD
      SLDH had three open reading frames (sldSLC) corresponding to the small, the
      large, and cytochrome c subunits of FAD-SLDH respectively. The deduced amino acid
      sequences showed high identity to those from G. oxydans IFO 3254: SldL showed to
      other FAD-enzymes, and SldC having three heme c binding motives to cytochrome c
      subunits of other membrane-bound dehydrogenases.

PMID- 15973044
TI  - Reconstitution of photosynthetic reaction centers and core antenna-reaction
      center complexes in liposomes and their thermal stability.
AB  - Photosynthetic reaction centers (RCs) and their core light-harvesting complexes
      (LH1-RCs), purified from a thermophile, Thermochromatium (T.) tepidum, and a
      mesophile, Allochromatium (A.) vinosum, were reconstituted into liposomes. The RC
      and the LH1-RC in the reconstituted liposomes were found intact from the
      absorption spectra at about 4 and 40 degrees C respectively. The thermal
      stability of the RCs of T. tepidum in the liposome was dependent on whether they
      were surrounded directly by lipids or by the core light-harvesting complexes. The
      results show that the RC of T. tepidum gains its thermostability through
      interactions with the LH1. These results are consistent with the result that the
      thermal stability of the LH1 in T. tepidum is similar in both the reconstituted
      LH1-RC liposome and ICM. This is clearly different from the mesophilic bacterium,
      A. vinosum. The thermal stability of RC was also affected by its subunit
      constitution: the RC containing a cytochrome subunit was more thermostable than
      the cytochrome-detached RC. This suggests that the cytochrome subunit might play
      a role in protecting the special pair pigments from denaturation. The thermal
      denaturation showed a second-order reaction dependence on time. The interaction
      of the pigments with proteins and/or lipids might be the cause of the second
      order reaction profile.

PMID- 15973045
TI  - Rice allergenic proteins, 14-16 kDa albumin and alpha-globulin, remain insoluble
      in rice grains recovered from rice miso (rice-containing fermented soybean
      paste).
AB  - The rice grains (RG) and rice seed proteins remaining in rice miso were
      investigated with a view point to the potential allergenicity of rice miso. RG
      ranging from 36 to 180 mg dry weight per g dry miso were separated from several
      samples of commercially available rice miso. Scanning electron microscopy of the
      recovered RG indicated that starch granules disappeared almost completely while
      protein bodies remained intact in RG. Most of the major seed proteins were
      extracted from RG by heating with 1% SDS/2% 2-mercaptoethanol and detected by SDS
      polyacrylamide gel electrophoresis. Major rice allergenic proteins, 14-16 kDa
      albumin (Alb14-16) and alpha-globulin (alpha-Glb) were also detected by
      immunoblotting using the specific antisera, and their contents were estimated to
      be 1.7 to 9.0 and 1 to 7 mg protein per g dry RG respectively. However, the major
      rice proteins, including glutelin and prolamin, in RG were insoluble in salt,
      alcohol, and urea solutions, but soluble in 6 M guanidine hydrochloride (Gu-HCl).
      By immunoblotting and ELISA, no Alb14-16 and only a slight amount of alpha-Glb
      were detected even in the 6 M Gu-HCl fraction, indicating that these major
      allergenic proteins are denatured and are present in an insoluble form in rice
      miso.

PMID- 15973046
TI  - Molecular phylogenetic diversity of the bacterial community in the gut of the
      termite Coptotermes formosanus.
AB  - The phylogenetic diversity of the bacterial community in the gut of the termite
      Coptotermes formosanus was investigated using a 16S rRNA gene clone library
      constructed by PCR. After screening by restriction fragment length polymorphism
      (RFLP) analysis, 49 out of 261 clones with unique RFLP patterns were sequenced
      and phylogenetically analyzed. Many of the clones (94%) were derived from
      Bacteroidales, Spirochaetes, and low G + C content gram-positive bacteria
      consisting of Clostridiales, Mycoplasmatales, Bacillales, and Lactobacillales. In
      addition, a few clones derived from Actinobacteria, Proteobacteria,
      Planctomycetes, Verrucomicrobia, and the candidate phylum "Synergistes" were also
      found. The most frequently identified RFLP type, BCf1-03, was assigned to the
      order Bacteroideales, and it constituted about 70% of the analyzed clones. The
      phylogenetic analysis revealed that the representative clones found in this study
      tended to form some clusters with the sequences cloned from the termite gut in
      several other studies, suggesting the existence of termite-specific bacterial
      lineages.

PMID- 15973047
TI  - Changes in the composition of xylem sap during development of the spadix of skunk
      cabbage (Symplocarpus foetidus).
AB  - The spadix of skunk cabbage, Symplocarpus foetidus, is thermogenic and maintains
      an internal temperature of around 20 degrees C even when the ambient air
      temperature drops below freezing. This homeothermic heat production is observed
      only during the stigma stage, and thereafter ceases at the male stage when pollen
      is shed. To clarify the regulatory mechanism by which the stigma stage-specific
      heat production occurs in the spadix, sugars, organic acids, and amino acids in
      xylem sap were analyzed and compared with those of post-thermogenic plants.
      Interestingly, no significant difference was observed in the total volume of
      xylem sap per fresh weight of the spadix between thermogenic (31.2+/-24.7 microl
      h(-1) g(-1)) and post-thermogenic (50.5+/-30.4 microl h(-1) g(-1)) plants.
      However, concentrations of sugars (sucrose, glucose, and fructose), organic acids
      (malate and succinate), and amino acids (Asp, Asn, Glu, Gln, Gly, and Ala) in
      xylem sap decreased remarkably in post-thermogenic plants. Our results indicate
      that the composition of the xylem sap differs during the development of the
      spadix of S. foetidus.

PMID- 15973048
TI  - Engineering of yeast Put4 permease and its application to lager yeast for
      efficient proline assimilation.
AB  - The Saccharomyces cerevisiae Put4 permease is significant for the transport of
      proline, alanine, and glycine. Put4p downregulation is counteracted by npi1
      mutation that affects the cellular ubiquitination function. Here we describe
      mutant Put4 permeases, in which up to nine lysine residues in the cytoplasmic N
      terminal domain have been replaced by arginine. The steady-state protein level of
      the mutant permease Put4-20p (Lys9, Lys34, Lys35, Lys60, Lys68, Lys71, Lys93,
      Lys105, Lys107 --> Arg) was largely higher compared to that of the wild-type
      Put4p, indicating that the N-terminal lysines can undergo ubiquitination and the
      subsequent degradation steps. Proline is the only amino acid that yeast
      assimilates with difficulty under standard brewing conditions. A lager yeast
      strain provided with Put4-20p was able to assimilate proline efficiently during
      beer fermentations. These results suggest possible industrial applications of the
      mutant Put4 permeases in improved fermentation systems for beer and other
      alcoholic beverages based on proline-rich fermentable sources.

PMID- 15973049
TI  - Two tandemly arranged ferredoxin genes in the Hydrogenobacter thermophilus
      genome: comparative characterization of the recombinant [4Fe-4S] ferredoxins.
AB  - A thermophilic, obligately chemolithoautotrophic hydrogen-oxidizing bacterium,
      Hydrogenobacter thermophilus TK-6, assimilates carbon dioxide via the reductive
      tricarboxylic acid cycle. A gene encoding a ferredoxin involved in this cycle as
      an electron donor (HtFd1) was cloned and sequenced. Interestingly, another
      ferredoxin gene (encoding HtFd2) was found in tandem with the HtFd1 gene. These
      two ferredoxin genes overlapped by four bp, and transcriptional analysis revealed
      that they are co-transcribed as an operon. The deduced amino acid sequences of
      HtFd1 and HtFd2 were 42.9% identical and each contained four cysteine residues
      that serve as probable ligands to an iron-sulfur cluster. Spectroscopic analyses
      of the purified recombinant ferredoxins heterologously expressed in Escherichia
      coli indicated that each ferredoxin contains a single [4Fe-4S]2+/1+ cluster.

PMID- 15973050
TI  - Glucan-binding activity of silkworm 30-kDa apolipoprotein and its involvement in
      defense against fungal infection.
AB  - The silkworm Bombyx mori 30-kDa lipoproteins (6G1 and 19G1), major components of
      the hemolymph, were shown to bind to glucans. 6G1 apolipoprotein was expressed as
      a fusion protein with glutathione S-transferase in Escherichia coli and assayed
      for its binding activity. The purified recombinant 6G1 apolipoprotein
      specifically bound to beta-glucan, but not to chitin, mannan, peptidoglycan, or
      oligosaccharide chains on glycoproteins. The beta-glucan binding of the
      recombinant 6G1 was inhibited by laminaribiose and laminarin, a soluble glucan,
      but not by lipopolysaccharide or insect blood sugar, trehalose at physiological
      concentration. Furthermore, the recombinant 6G1 was shown to participate in the
      activation of prophenoloxidase cascade and to interfere with hyphal growth of the
      entomopathogenic fungus Paecilomyces tenuipes, injected into pupae of B. mori.
      These results suggest that 6G1 lipoprotein plays a role in the protection of B.
      mori against invading fungi.

PMID- 15973051
TI  - Effects of fenugreek seed extract in obese mice fed a high-fat diet.
AB  - It was found that fenugreek seed extract reduced the body weight gain induced by
      a high-fat diet in obese mice. The extract decreased plasma triglyceride gain
      induced by oil administration. The major component of the extract, 4
      hydroxyisoleucine, also decreased plasma triglyceride gain. Consequently,
      fenugreek seed extract is expected to prevent the obesity induced by a high-fat
      diet.

PMID- 15973052
TI  - Involvement of SDS-stable higher M(r) forms of bovine normal milk alpha
      lactalbumin in inducing intestinal IEC-6 cell death.
AB  - Monomeric 14-kDa bovine alpha-lactalbumin was purified with a preparation of
      lower molecular weight whey protein concentrate from Holstein cow normal milk
      followed by size exclusion chromatography. The protein showed a stimulatory
      rather than an inhibitory effect on the proliferation of a cultured IEC-6 cell
      line from the rat small intestine. But incubation in 30% trifluoroethanol/acetate
      buffer (pH 5.5) at 37 degrees C for 5 d in a slowly rotating test tube rendered
      it highly cytotoxic with concomitant appearance of SDS-stable 20- and 30-kDa
      forms of alpha-lactalbumin on electrophoresis. Furthermore, alpha-lactalbumin
      obtained by a one-step purification procedure by affinity chromatography on an
      anti-alpha-lactalbumin antibody column from the lower molecular weight whey
      protein concentrate, which had been found to contain several SDS-stable higher
      M(r) forms of alpha-lactalbumin, exhibited potent inhibitory activity on IEC-6
      cell growth. These results indicate the involvement of SDS-stable higher M(r)
      forms of bovine normal milk alpha-lactalbumin in inducing cell death on the
      intestinal IEC-6 cell line.

PMID- 15973053
TI  - Sequencing of hemoglobin gene 4 (dmhb4) and Southern blot analysis provide
      evidence of more than four members of the Daphnia magna globin family.
AB  - A genomic fragment containing the hemoglobin gene dmhb4 of Daphnia magna was
      cloned and its nucleotide sequence determined. Concerning induction under hypoxic
      conditions, dmhb4 was found to be expressed constitutively with similar mRNA
      quantities in D. magna bred in either normoxic or hypoxic medium. Southern blot
      analysis revealed at least six hemoglobin-like sequences in the genome of Daphnia
      magna.

PMID- 15973054
TI  - Purification and characterization of a new endo-1,4-beta-D-glucanase from
      Beltraniella portoricensis.
AB  - A new endoglucanase, designated BCE1, produced by Beltraniella portoricensis, was
      purified from the culture supernatant. The N-terminal amino acid sequence
      suggests that BCE1 belongs to family 45 glycoside hydrolase (family 45
      endoglucanase). The molecular mass of BCE1 was found to be 40 kDa by sodium
      dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The optimum pH for
      the carboxymethyl cellulase (CMCase) activity of BCE1 was 4.5, and the optimum
      temperature was 55 degrees C. Among family 45 endoglucanases, RCE1 and RCE2 from
      Rhizopus oryzae, PCE1 from Phycomyces nitens, and EGL3 and EGL4 from Humicola
      grisea, BCE1 was most resistant to anionic surfactant and oxidizing agent. These
      results indicate that BCE1 might prove to be a useful enzyme in the detergent
      industry.

PMID- 15973055
TI  - Quinolactacide, a new quinolone insecticide from Penicillium citrinum Thom F
      1539.
AB  - By a screening program searching for new pesticides from fungal sources, an
      insecticidal compound was isolated from Penicillium citrinum F 1539. The
      compound, named quinolactacide, was novel and showed 88% mortality against green
      peach aphids (Myzus persicae) at 250 ppm. Its structure was determined by
      spectroscopic techniques.

PMID- 15973056
TI  - Characterization of refolded hen lysozyme variant lacking two outside disulfide
      bonds.
AB  - We characterized a refolded hen lysozyme variant containing only two SS-bonds,
      C64-C80 and C76-C94 (4CAHEL). From CD spectra and its activity, it was found that
      the refolded 4CAHEL has a structural topology analogous to wild-type lysozyme
      (WTHEL). Moreover, the refolded 4CAHEL showed no thermal transition, indicating
      that it had a character like a molten globule.

PMID- 15973057
TI  - Protein-protein interactions in the subunits of ribonuclease P in the
      hyperthermophilic archaeon Pyrococcus horikoshii OT3.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein complex involved in the
      processing of the 5' leader sequence of precursor tRNA (pre-tRNA). RNase P in the
      hyperthermophilic archaeon Pyrococcus horikoshii OT3 consists of RNA and five
      protein subunits (Ph1481p, Ph1496p, Ph1601p, Ph1771p, and Ph1877p). In vivo
      interactions among five protein subunits of RNase P in P. horikoshii OT3 were
      examined using a yeast two-hybrid system. The analysis indicates that proteins
      Ph1481p and Ph1601p interact strongly with Ph1877p and Ph1771p respectively,
      whereas Ph1481p interacts moderately with Ph1601p. In contrast, no interaction
      was detected between Ph1496p and the other four proteins. Co-immunoprecipitation
      analysis confirmed the interactions obtained by yeast two-hybrid assay.

PMID- 15973058
TI  - Characterization of halophilic alkaline phosphatase from Halomonas sp. 593, a
      moderately halophilic bacterium.
AB  - A halophilic alkaline phosphatase was highly purified (about 510-fold with about
      21% yield) from a moderate halophile, Halomonas sp. 593. The N-terminal 35 amino
      acid sequence of this enzyme was found to be more acidic than those previously
      isolated from Vibrio spp., and this enzyme was partially resistant to SDS.
      Several enzymatic properties demonstrated that it showed higher halophilicity
      than those enzymes from Vibrio spp.

PMID- 15973059
TI  - Characterization of spore germination of a thermoacidophilic spore-forming
      bacterium, Alicyclobacillus acidoterrestris.
AB  - The germination behaviors of spores of Alicyclobacillus acidoterrestris, which
      has been considered to be a causative microorganism of flat sour type spoilage in
      acidic beverages, were investigated. The spores of A. acidoterrestris showed
      efficient germination and outgrowth after heat activation (80 degrees C, 20 min)
      in Potato dextrose medium (pH 4.0). Further, the spores treated with heat
      activation germinated in McIlvaine buffer (pH 4.0) in the presence of a
      germinative substance (L-alanine) and commercial fruit juices, although not in
      phosphate buffer (pH 7.0). Heat activation was necessary for germination. The
      spores of A. acidoterrestris, which easily survived the heat treatment in acidic
      conditions, lost their resistance to heat during germination. Our results suggest
      that the models obtained from spore germination of A. acidoterrestris might be
      beneficial to determine adequate thermal process in preventing the growth of
      potential spoilage bacteria in acidic beverages.

PMID- 15973060
TI  - High-velocity gunshot wounds to the head: analysis of 135 patients.
AB  - Head injuries due to high-velocity missiles and shrapnel as a result of military
      conflicts have become a very important cause of death or severe neurological
      deficits. Military-type missiles have high velocities and transfer higher amounts
      of energy to neural tissue, compared to civil-type missiles. This physical
      phenomenon also causes greater neural tissue destruction. Shrapnel particles
      derive from blasts and cause less severe injury because of the irregular particle
      shape and low energy transmission. This study analyzed 135 patients with head
      trauma, 80 patients (59%) injured by missiles and 55 patients (41%) by shrapnel.
      Glasgow Coma Scale (GCS) scores at admission were 3 to 7 in 69 patients, 8 to 10
      in 29 patients, and 11 to 15 in 37 patients. The most common anatomical
      localizations were the right frontoparietal region in 42 patients and the left
      frontoparietal region in 40 patients. One hundred patients (74%) were operated on
      immediately and 35 patients (26%) were treated conservatively in the intensive
      care unit. Ten of the 135 patients died (7.4%), seven from missile injury and
      three from shrapnel injury. In this study, we found that high mortality was
      associated with low GCS score at admission, presence of multilobar or skull base
      injuries, and involvement of ventricles. Early and aggressive surgical
      intervention decreased the mortality.

PMID- 15973061
TI  - Experimental model of intracranial arteriovenous shunting in the acute stage.
AB  - A model of intracranial arteriovenous (AV) shunting must incorporate local
      hypoperfusion and simulate the hemodynamics of arteriovenous malformations. In
      this study, the hemodynamics of an intracranial AV shunt model in the acute stage
      were clarified. End-to-side anastomoses with a femoral vein graft were performed
      between a cortical branch of the middle cerebral artery (MCA) and the superior
      sagittal sinus in anesthetized dogs. Local cerebral blood flow (l-CBF) was
      measured by laser Doppler blood flowmetry. l-CBF decreased suddenly by 34.2% when
      the shunt was opened in the ipsilateral MCA territory. Upon re-occlusion, l-CBF
      immediately equaled or exceeded the pre-opening value and returned to the pre
      opening value within the next 15 minutes. Opening the shunt produced little
      change in l-CBF in the territory of the ipsilateral or contralateral anterior
      cerebral artery. The decrease in l-CBF was correlated with shunt volume only in
      the MCA territory. l-CBF manifested a PaCO(2)-dependent increase before shunt
      opening, but CO(2) reactivity was impaired after opening the shunt only in the
      MCA territory. This dog model features local hypoperfusion due to intracranial AV
      shunting and disturbance of CO(2) reactivity in the acute stage. The hemodynamics
      of this model will be confirmed in the chronic stage.

PMID- 15973062
TI  - Comparative clinical study of the anti-emetic effects of oral ramosetron and
      injected granisetron in patients with malignant glioma undergoing ACNU
      chemotherapy.
AB  - The effectiveness of ramosetron tablets and granisetron injection was compared
      for reducing the frequency of nausea, vomiting, and anorexia in patients with
      malignant glioma undergoing ACNU chemotherapy. Patients with malignant glioma to
      be treated with ACNU chemotherapy were randomly assigned to receive oral
      ramosetron (20 patients) or intravenous granisetron (19 patients) prior to ACNU
      injection. Gastrointestinal toxicity within 48 hours of ACNU injection was
      compared to that in patients who had received ACNU chemotherapy with dopamine D2
      receptor-blocker as a historical control group. Within 24 hours of the
      administration of ACNU, 15 of the 20 patients treated with ramosetron and 16 of
      the 19 treated with granisetron were nausea-free, and 14 of the former and 14 of
      the latter regained their normal appetite. There was no significant difference in
      the anti-emetic effects. Ten of the 17 controls experienced no vomiting within 6
      hours of the injection of ACNU, five were nausea-free within 24 hours, and two
      retained their normal appetite within 24 hours. Oral ramosetron has the same anti
      anorectic and anti-emetic effects as intravenous granisetron. Ramosetron tablets
      are less expensive and are easy to take, so should be on the list of first-choice
      anti-emetic drugs for patients treated with ACNU chemotherapy.

PMID- 15973063
TI  - Sagittal magnetic resonance imaging of intramural hematoma from non-traumatic
      dissection of the anterior cerebral artery. Case report.
AB  - A 46-year-old woman presented with non-traumatic anterior cerebral artery
      dissection manifesting as sudden onset of headache and motor weakness of the
      right lower limb. Angiography revealed luminal narrowing of the left anterior
      cerebral artery from the A(3) portion to the distal portion. Sagittal T(1)
      weighted magnetic resonance imaging showed hyperintensity due to an intramural
      hematoma around the flow void signal of the affected anterior cerebral artery.
      Sagittal magnetic resonance imaging should be performed in suspected cases of
      anterior cerebral artery dissection to detect the diagnostic finding of
      intramural hematoma.

PMID- 15973064
TI  - Early revascularization in a patient with perfusion computed tomography/diffusion
      weighted magnetic resonance imaging mismatch secondary to acute vertebral artery
      occlusion. Case report.
AB  - A 67-year-old woman with a recent history of recurrent ischemic stroke secondary
      to right vertebral artery stenosis suffered acute onset of left homonymous
      hemianopsia and the medial longitudinal fasciculus syndrome, which resolved with
      hyperdynamic therapy. However, consciousness deteriorated 6 hours later.
      Perfusion computed tomography (CT) revealed regions of prolonged mean transit
      time in the bilateral cerebellar hemispheres, vermis, brainstem, and right
      occipital lobe, which were more extensive than the ischemic lesions demonstrated
      by diffusion-weighted magnetic resonance (MR) imaging. Subsequent cerebral
      angiography showed occlusion of the right vertebral artery. The patient underwent
      emergent left superficial temporal artery to left superior cerebellar artery
      bypass. Postoperatively she demonstrated resolution of the preoperative perfusion
      CT/diffusion-weighted MR imaging mismatch and improved neurological deficits.
      Early revascularization in a patient with perfusion CT/diffusion-weighted MR
      imaging mismatch following acute vertebrobasilar stroke can lead to improvement
      in cerebral perfusion and neurological function.

PMID- 15973065
TI  - Rapidly growing microcystic meningioma of the middle fossa floor. Case report.
AB  - A 74-year-old woman presented with a microcystic meningioma which manifested as
      mental disturbance. A rapidly growing tumor in the left middle fossa had not been
      detected by examination 10 months before. The tumor was remarkably enhanced by
      contrast medium on both computed tomography and magnetic resonance imaging and
      was associated with massive perifocal edema. Cerebral angiography revealed that
      the tumor was mainly fed by the left middle meningeal artery, which was embolized
      preoperatively. The tumor was completely removed and no postoperative adjuvant
      therapy was administered. The histological diagnosis was microcystic meningioma
      with many mitotic figures and a MIB-1 labeling index of 12.8%. Four months later,
      the tumor recurred and invaded the paranasal sinus. Focal irradiation
      successfully controlled further regrowth. This case suggests that microcystic
      meningioma may have aggressive features, and close observation is necessary even
      after gross total removal.

PMID- 15973066
TI  - Spontaneous resolution of residual pituitary adenoma. Case report.
AB  - A 34-year-old man presented with progressive diminution of vision in the left eye
      for 7 years. He had suffered left hemicranial headache associated with left retro
      orbital pain and diplopia for 3 months. Magnetic resonance (MR) imaging revealed
      a pituitary tumor located in the sella and extending into the right cavernous
      sinus. After transsphenoidal surgery, the vision improved drastically but the
      diplopia persisted. Postoperative MR imaging showed residual tumor in the right
      cavernous sinus. Follow-up examination after 3 years showed the diplopia had
      completely recovered and the residual tumor in the cavernous sinus had
      disappeared. Spontaneous resolution of a large intracavernous sinus residue of a
      pituitary adenoma may occur due to tumor necrosis.

PMID- 15973067
TI  - Cerebral composite atypical teratoid/rhabdoid tumor and yolk sac tumor in the
      frontal lobe of an infant. Case report.
AB  - A 1-year-old male infant presented with a rare cerebral composite tumor
      consisting of atypical teratoid/rhabdoid tumor (AT/RT) with epithelial and
      mesenchymal components and yolk sac tumor (YST) with Schiller-Duval bodies. He
      was admitted to our medical center with a 2-month history of right hemiparesis.
      Computed tomography and magnetic resonance imaging revealed a large, intra-axial
      solid tumor with a cyst in the left frontal lobe. Total resection of the tumor
      was performed. Histological examination showed two different main growth
      patterns: solid sheets of undifferentiated polygonal cells and a few rhabdoid
      cells with rosette structures and rhabdomyoblastic cells; and reticular or
      papillary structures with occasional Schiller-Duval bodies in a myxoid matrix.
      The immunohistochemical and electron microscopy findings indicated composite
      AT/RT and YST. Initial total resection of the tumor was subsequently followed by
      local recurrence, hydrocephalus, and spinal metastasis. Despite adjuvant
      chemotherapy, the patient died 9 months after admission. AT/RT is a recently
      established entity of the central nervous system. The present case of composite
      AT/RT and YST in the frontal lobe indicates the poor prognosis of such tumors.

PMID- 15973068
TI  - Transethmoidal meningoencephalocele in an elderly woman. Case report.
AB  - A 69-year-old woman presented with a transethmoidal meningoencephalocele
      manifesting as gradually developing anosmia. Examinations revealed a mass in the
      nasal cavity associated with multiple angiomas in her lip and orbit. Neuroimaging
      showed meningoencephalocele extending via the ethmoid sinus to the nasal cavity.
      She had no history of craniofacial trauma and intranasal or intracranial
      operation, and no skull base tumor was detected. Frontal base reconstruction was
      performed with a two-layer vascularized flap to prevent cerebrospinal fluid
      leakage. The dural defect was repaired with the pericranial flap, and the bony
      defect of the cribriform plate was reconstructed using the reversed U-shaped
      split temporalis musculofascial flap. Transethmoidal meningoencephalocele is a
      rare congenital malformation and almost half of the cases are identified in the
      first year of life. We should be aware of this clinical pathology and avoid
      unexpected rhinorrhea in elderly patients. The most important aspect of the
      operation is watertight closure of the patent passage to the intracranial
      compartment. The reversed U-shaped split temporalis musculofascial flap is useful
      to reconstruct the midline frontal base defect.

PMID- 15973069
TI  - Blurred vision caused by inflammation of the optic nerves due to a pituitary
      abscess.
AB  - A 48-year-old woman was admitted to our institution complaining of headache and a
      2-month history of blurred vision and increased urinary volume. T(1)-weighted
      magnetic resonance (MR) imaging with gadolinium showed a ring-enhanced mass
      lesion in the pituitary. Fluid-attenuated inversion recovery MR imaging showed
      high-intensity lesions in the optic nerves, hypothalamus, and thalamus. The
      histological diagnosis was pituitary abscess. The blurred vision was caused by
      inflammation, but not compression, of the optic nerves due to the pituitary
      abscess outside the hypophysis.

PMID- 15973070
TI  - [The cavernous hemangioma of the colon inducing massive hematochezia and treated
      by endoscopic polypectomy].

PMID- 15973071
TI  - [Pharmacological therapy of portal hypertension--focused on Korean data].
AB  - Portal hypertension as a consequence of liver cirrhosis is responsible for
      serious complications such as variceal bleeding, ascites and hepatic
      encephalopathy. Successful pharmacological treatment of portal hypertension can
      prevent the risk of the variceal bleeding, and contribute to reduce the morbidity
      and mortality in patients with liver cirrhosis. To identify the effect of drugs
      on portal hypertension, portal pressure was evaluated accurately before and after
      the drug administration. The hepatic venous pressure gradient has been accepted
      as the gold-standard method for assessing the severity of portal hypertension and
      the response to drug treatment. The mean hepatic venous pressure gradient was
      15.1+/-5.4 mmHg in Korean cirrhotic patients who had experienced variceal
      bleeding. Non-selective beta blockers are the treatment of choice for primary and
      secondary prevention of variceal bleeding. The dose of propranolol should be
      subsequently adjusted until the resting heart rate had been reduced by 25% or
      less than 55 beats per minute. It has been reported that the optimal dose of
      propranolol is variable due to racial differences in cardiovascular receptor
      sensitivity. In Korean patients with portal hypertension and liver cirrhosis, the
      mean required dose of propranolol to reach target heart rate was 165 mg (range;
      80-280 mg). This review covers mainly the results of the pharmacological therapy
      of portal hypertension in Korean cirrhotic patients.

PMID- 15973072
TI  - [Is the invasive approach for all the upper gastrointestinal mesenchymal tumors
      necessary?].
AB  - BACKGROUND/AIMS: Mesenchymal tumors are the most frequent submucosal tumors in
      gastrointestinal trail. We reviewed the mesenchymal tumors which are confirmed by
      pathology to examine whether the invasive approach of all mesenchymal tumors is
      necessary. METHODS: This study was performed on fifty-nine patients who has
      mesenchymal tumors confirmed by endoscopic or surgical resection from January
      2000 to June 2004. RESULTS: Mesenchymal tumors consisted of thirty-six
      gastrointestinal stromal tumors (GISTs), 20 leiomyomas and 3 schwannomas. All the
      esophageal tumors were leiomyoma (12/12, 100%). In stomach, there were 32 GISTs
      (76.2%), 7 leiomyomas (16.7%) and 3 schwannomas (7.1%). And there were 4 GISTs
      (80.0%) and 1 leiomyoma (20.0%) in duodenum. Tumors less than 1 cm in maximal
      diameter were leiomyoma or GISTs with very low risk of aggressive behavior. 56.1%
      of the tumors larger than 1 cm consisted of low, intermediate or high risk GISTs.
      CONCLUSIONS: Biopsy must be considered according to its size and anatomic
      location of mesenchymal tumors. The invasive approach for every esophageal
      submucosal tumor is not necessary unless the size is very large, because most of
      them are benign in nature. However, the gastric submucosal tumor with more than 1
      cm in diameter should be carefully and regularly followed up or biopsied because
      it cannot be assumed to be benign for any GIST more than 1 cm in size at the
      present time, safely.

PMID- 15973073
TI  - [Immunohistochemical expression of bcl-2, bcl-xL, bax, p53 proteins in gastric
      adenoma and adenocarcinoma].
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the immunohistochemical
      expression of bcl-2, bcl-xL, bax, and p53 proteins according to the pathological
      parameters such as grade of dysplasia, histological type, depth of invasion,
      lymph node metastasis, and TNM stage in the gastric adenoma and gastric
      adenocarcinoma. METHODS: Immunohistochemical staining using monoclonal bcl-2, bcl
      xL, bax, p53 antibodies were performed on paraffin embedded specimens from forty
      one gastric adenomas and 100 gastric adenocarcinomas. RESULTS: The expression
      rate of bcl-2 was higher in adenomas (34.2%), especially in high grade dysplasia
      (52.4%), than adenocarcinomas (2.0%). The expression rate of bcl-xL was higher in
      adenocarcinomas (55.0%) than adenomas (22%). The expression rate of the bax was
      higher in adenocarcinomas (58.0%) than adenomas (14.6%). In the adenocarcinoma,
      the bax expression was significantly related with the depth of invasion, lymph
      node metastasis, and TNM stage. The expression rate of p53 was higher in
      adenocarcinomas (64.0%) than adenomas (14.6%). CONCLUSIONS: Bcl-2 protein would
      be related with the development of gastric adenoma, especially with high grade
      dysplasia. Bcl-xL and p53 proteins would be involved in the development of
      relatively early stage of gastric adenocarcinoma but not in tumor progression.
      Bax protein would be involved in the development of gastric adenocarcinoma and
      related with depth of invasion, lymph node metastasis, and TNM stage.

PMID- 15973074
TI  - [The expression of matrix metalloproteinases (MMPs), tissue inhibitor of
      metalloproteinases (TIMPs) and angiogenesis in relation to the depth of tumor
      invasion and lymph node metastasis in submucosally invasive colorectal
      carcinoma].
AB  - BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of
      patients with submucosally invasive colorectal carcinoma. This study was
      performed to determine the role of matrix metalloproteinases (MMPs), tissue
      inhibitors of metalloproteinases (TIMPs) production and microvessel formation on
      the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total
      of forty-one subjects with surgically resected submucosally invasive colorectal
      carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP
      9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed.
      Angiogenesis was evaluated by counting the number of microvessels in each
      pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS:
      The depth of submucosal invasion was not significantly correlated with the
      expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen
      activator, but the microvessel count was significantly correlated with the
      absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was
      positively correlated with adjacent lymphatic invasion (p<0.05) and increased
      TIMP-2 expression was correlated with LN metastasis in submucosally invasive
      colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the
      expression of TIMP-2 and the microvessel count may be useful parameters for
      considering additional surgery after endoscopic treatment of submucosally
      invasive colorectal carcinoma.

PMID- 15973075
TI  - [Clinical significance of incidentally detected bowel wall thickening on
      abdominal computerized tomography scan].
AB  - BACKGROUND/AIMS: Due to widespread use of computerized tomography (CT) scan to
      examine patients with variable disease or complaints, detection of incidental or
      unsuspected gastrointestinal abnormalities are not uncommon. Clinical
      significance of incidentally detected bowel wall thickening (BWT) on abdominal CT
      scan is uncertain at present. Despite the necessity for the clinical guidelines
      describing the evaluation of incidental bowel wall thickening on CT scan, there
      have been few studies concerning these radiological abnormalities. Our objective
      was to determine whether endoscopic evaluation is necessary for the evaluation of
      these abnormal findings. METHODS: This study evaluated one hundred and forty
      patients with incidentally detected BWT on abdominal CT scan in Inje University
      Sanggye Paik Hospital from 2001 to 2003. 102 patients of those were proceeded by
      endoscopic evaluation. Forty-eight patients had received upper endoscopy, 26
      patients had colonoscopy, while 28 patients had sigmoidoscopy. RESULTS:
      Endoscopic work up revealed significant abnormalities in 83% of patients with
      incidental findings of the distal esophagus, 73% of patients with thickening of
      the stomach, 35% of patients with thickening of the right colon, and 71% of
      patients with thickening of the sigmoid colon and rectum. CONCLUSIONS: Although
      significant pathologic findings are less common in thickening of the right colon
      than other bowel wall thickening, all of these incidental findings on CT scan
      warrant further endoscopic evaluation.

PMID- 15973076
TI  - [Abnormal electron microscopic findings of nonalcoholic steatohepatitis and
      related factors].
AB  - BACKGROUND/AIMS: In spite of increasing interests about nonalcoholic
      steatohepatitis (NASH), there are few reports about the ultrastructure of
      hepatocyte in this disease. The aim of this study was to clarify abnormal
      electron microscopic (EM) findings and related factors in NASH. METHODS: Total of
      fourteen patients who underwent liver biopsy due to steatohepatitis were
      included. Precise personal history was taken and variable blood tests such as
      liver function test, lipid profile, and serum iron study were done. Pathologic
      examination with light and electron microscopy was done by single pathologist.
      RESULTS: Eleven men and three women were included and mean age was 33.7+/-12.8
      years. Nine patients drinking less than 40 g/week was grouped as "NASH group" and
      other 5 patients drinking more than 40 g/week and body mass index less than 25
      was grouped as "ASH (Alcoholic Steatohepatitis) group". Polymorphism of
      mitochondria such as megamitochondria or loss of cristae was major abnormal EM
      findings and was more common in "NASH group" than "ASH group" (p=0.027). There
      was no significant clinical or pathological factors related with the presence of
      these abnormal EM findings. CONCLUSIONS: Polymorphism of mitochondria is major
      abnormal EM finding of steatohepatitis and is more common in NASH than ASH. And
      there is no significant clinical or pathological factors which could predict the
      presence of these abnormal EM findings.

PMID- 15973077
TI  - Prognostic significance of p53 overexpression after hepatic resection of
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: p53 mutation is the most common genetic abnormality in human
      cancers. However, although it has been reported that p53 overexpression in
      hepatocellular carcinoma (HCC) is associated with the aggressive behavior of
      tumor, the prognostic significance of p53 overexpression in HCC remains
      controversial. The aims of the present study were to examine the correlations
      between p53 overexpression and the clinicopathologic parameters of HCCs, and to
      determine the prognostic significance of p53 overexpression in HCC. METHODS:
      Immunohistochemical analysis of p53 overexpression was performed in 105
      consecutive cases of HCC who underwent curative hepatic resection. Survival
      curves were calculated using the Kaplan-Meier method and multivariate analysis of
      outcome predictors for HCCs was assessed by logistic regression analysis.
      RESULTS: p53 overexpression was observed in 20 of 105 HCCs (19.0%). Multivariate
      analysis identified significant correlations between p53 overexpression and
      microvascular invasion (p=0.027), liver cirrhosis (p=0.035), 1-year survival rate
      (p=0.016), multiple tumors (p=0.014), and the presence of tumor capsule
      (p=0.010). The 2-year survival rate was poorer in patients without tumor capsule
      (p=0.043). CONCLUSIONS: Our results show a positive association between p53
      overexpression and microvascular invasion in HCC, and indicate that p53
      overexpression is a poor prognostic factor of survival, especially within 1 year
      after liver resection in HCC patients.

PMID- 15973078
TI  - [A case of giant gastric villous tumor with carcinomatous change].
AB  - Villous tumors of the stomach are somewhat rare with approximately 100 cases only
      reported in the literatures and have tendency to undergo malignant transformation
      as high as 72%. They are frequently multiple and associated with other
      gastrointestinal neoplasm. Thirty percent of them are associated with an
      independent gastric carcinoma. Gastric villous tumor has certain radiologic
      characteristics that may permit a preoperative diagnosis and also some
      distinctive clinicopathologic features which make early diagnosis and proper
      treatment possible. We experienced a 64-year-old man who complained of prolonged
      general weakness, weight loss for several months and left upper quadrant pain for
      four days. Esophagogastroduodenoscopy and barium study of upper gastrointestinal
      tract demonstrated typical, irregular, frond-like surfaced villous tumor
      occupying nearly whole gastric lumen and located eccentrically along the lesser
      curvature side. Endoscopic biopsy of the tumor revealed a gastric villous tumor
      with carcinomatous change.

PMID- 15973079
TI  - [A case of hepatocellular carcinoma complicating cardiac cirrhosis caused by
      constrictive pericarditis].
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies. Many
      factors are considered to be etiology associated with HCC; the important factors
      are hepatitis B and C viruses and alcohol. Cirrhosis is present in the majority
      of patients with HCC. It is assumed that all diseases, which lead to liver
      cirrhosis, may be complicated by the development of HCC. We report a 36-year-old
      man with HCC which developed from cardiac cirrhosis caused by constrictive
      pericarditis in whom both hepatitis B virus and hepatitis C viral marker tests
      were all negative. CT scan of his heart showed pericardial calcification with
      diastolic dysfunction of right ventricle. Abdominal CT scan revealed mottled
      mosaic pattern of contrast enhancement of liver parenchyme and two hepatic
      lesions that were considered to be HCCs. Left lateral segmentectomy of liver was
      performed. There were two well-circumscribed masses which were confirmed to be
      HCC and the remaining hepatic parenchyma showed bridging fibrosis between central
      zonal regions. To our knowledge, this is the first case of HCC complicating
      cardiac cirrhosis in Korea.

PMID- 15973080
TI  - [A case of osteoclast-like giant cell tumor of the pancreas].
AB  - Osteoclast-like giant cell tumor of the pancreas is a very rare tumor. Despite
      their striking morphologic resemblance to certain mesenchymal tumors of bone and
      tendon sheath, it has been suggested that these tumors may arise from epithelial
      precursors. This unusual tumor presents in the 6th or 7th decade with a nearly
      equal gender ratio. Pure forms of osteoclast-like giant cell tumor have a better
      prognosis because they have a predilection to local spread, are slower to
      metastasize and rarely metastasize to lymph nodes, but these forms are very rare.
      We present an osteoclast-like giant cell tumor arising in the body of the
      pancreas in a 71 year-old male patient. The tumor was composed of two major cell
      types: atypical mononuclear cells and abundant osteoclast-like multinucleated
      giant cells. Immunohistochemical studies showed that atypical cells were strongly
      reactive for vimentin and focally reactive for cytokeratin. In contrast, the
      giant cells were immunoreactive for CD68, but negative for cytokeratin. Three
      months later, the tumor size increased and liver metastasis was newly developed.
      He died at 11 months after the diagnosis.

PMID- 15973081
TI  - [Photodynamic therapy for unresectable cholangiocarcinoma: does it really
      increase the survival time?].

PMID- 15973085
TI  - Reliability of graded exercise testing after traumatic brain injury: submaximal
      and peak responses.
AB  - OBJECTIVE: To assess the reliability of the submaximal and peak responses to a
      treadmill graded exercise test in individuals recovering from traumatic brain
      injury. DESIGN: A total of 15 individuals (11 men, 4 women; 28.5 +/- 9.2 yrs)
      with moderate to severe traumatic brain injury admitted into a postacute
      residential treatment center 10 +/- 7 mos after injury performed two treadmill
      graded exercise tests separated by 4-8 days. Heart rate, oxygen consumption (in
      milliliters per minute per kilogram), minute ventilation (in liters per minute),
      and respiratory exchange ratio (carbon dioxide output/oxygen consumption) were
      continuously monitored at 1-min intervals. Submaximal and peak values were
      analyzed for absolute level of agreement using the intraclass correlation
      coefficient. RESULTS: The submaximal intraclass correlation coefficient values
      for all variables between minutes 3 and 7 ranged from 0.80 to 0.93. Submaximal
      intraclass correlation coefficients before and in the subsequent minutes were
      less than optimal for heart rate and minute ventilation. Lower intensity
      workloads elicited slightly better agreement than higher intensity workloads. The
      peak response intraclass correlation coefficients ranged from 0.77 (heart rate)
      to 0.92 (oxygen consumption). CONCLUSION: Despite the presence of other co
      morbidities, subjects recovering from traumatic brain injury provided consistent
      individual responses, allowing for reliable assessments of cardiorespiratory
      conditioning programs. Assessments of ambulatory efficiency, endurance, and
      aerobic fitness adaptations as a result of treatment for persons with traumatic
      brain injury should include analyses of submaximal responses to graded exercise.

PMID- 15973084
TI  - Body composition and water compartment measurements in boys with Duchenne
      muscular dystrophy.
AB  - OBJECTIVE: Duchenne muscular dystrophy (DMD) patients have a lower percentage of
      total body water and higher extracellular water to intracellular water (ECW/ICW)
      ratio compared with normal subjects. However, it is not known whether this is due
      to increased fat mass or a decreased amount of ICW in muscle cells in DMD
      patients. The purpose of this study was to (1) determine the effect of increased
      fat mass and decreased lean mass on the ECW to ICW ratio in DMD patients and to
      (2) determine the validity of multifrequency bioelectrical impedance analysis
      (MFBIA) in assessing body composition in DMD patients. DESIGN: This study has a
      quasi-experimental, comparative design using nonequivalent groups. A total of 46
      boys ranging from 6 to 13 yrs of age participated in this study. There were 12
      nonobese able-bodied controls, 19 obese able-bodied children (obese), and 15 boys
      with DMD. Body composition was measured by dual-energy x-ray absorptiometry
      (DEXA). Body composition and body water compartment analysis were assessed by
      MFBIA. All measurements obtained using MFBIA were compared with those obtained
      using DEXA for validation. RESULTS: Both MFBIA and DEXA measures were strongly
      correlated in control (r = 0.99), obese (r = 0.92), and DMD subjects (r = 0.95).
      However, lean tissue mass measured by DEXA in the DMD subjects was only slightly
      higher (19.2 +/- 1.1 vs. 18.2 +/- 1.2, P < 0.02) than as measured by MFBIA. Mean
      percentage of body fat measured by DEXA in the DMD subjects (30.4 +/- 3.1%) was
      significantly lower than as measured by MFBIA (38.7 +/- 2.2%). The mean
      percentage of body fat measured by DEXA in the control group (23.2 +/- 1.8%) was
      significantly (P < 0.001) lower than as measured by MFBIA (28.6 +/- 1.6%). The
      mean percentage of body fat measured by DEXA in obese able-bodied controls (40.8
      +/- 0.9%) was not significantly different from that measured by MFBIA (40.4 +/-
      1.5%). Compared with the obese and control subjects, DMD subjects showed reduced
      ICW and ECW, with an increased ECW/ICW ratio, as expected. However, the
      percentage of fat for the DMD group was not different from the obese group.
      CONCLUSIONS: DMD patients have elevated ECW/ICW ratios compared with obese
      subjects and nonobese controls. However, obese subjects and nonobese controls had
      similar ECW/ICW ratios, despite the increased fat tissue mass in obese subjects.
      This suggests that the elevated ECW/ICW ratios in DMD subjects are not due to
      increased fat mass but rather some other mechanism, likely impaired cellular
      homeostasis due to muscle membrane instability. Although MFBIA slightly
      underestimates lean tissue mass in boys with DMD, it has a potential role as an
      inexpensive and easy to use measurement tool to measure changes in muscle mass in
      the clinical setting.

PMID- 15973086
TI  - Paretic hand rehabilitation with constraint-induced movement therapy after
      stroke.
AB  - OBJECTIVE: Hemiparesis of the upper limb after stroke can be severely disabling.
      We studied the effectiveness of constraint-induced movement therapy in improving
      motor abilities in very chronic stroke subjects. We assessed whether the obtained
      changes, if any, would endure after the intervention program. DESIGN:
      Participants were 27 consecutive chronic stroke subjects (mean age, 56 +/- 13
      yrs) who fulfilled specific motor criteria. The design was an uncontrolled
      preintervention to postintervention comparison. The subjects participated in a 2
      wk-long constraint-induced movement therapy program. The motor function of the
      affected arm and its daily use were assessed using a structured motor performance
      test in a control test 2 wks before the intervention, then again immediately
      before and after the intervention, and at the follow-up. The intervention was
      undertaken in a rehabilitation hospital. RESULTS: The motor abilities of the
      affected arm improved significantly as measured by the structured motor
      performance test. The obtained improvements in the affected arm motor behavior
      endured for 5 mos after the therapy. CONCLUSIONS: Chronic stroke subjects, who
      have sufficient residual motor control for exercise, benefit from highly
      concentrated therapy and can still enhance their voluntary motor control of the
      affected arm even years after the incident.

PMID- 15973087
TI  - Factor structure of the Trinity Amputation and Prosthesis Experience Scales
      (TAPES) with individuals with acquired upper limb amputations.
AB  - OBJECTIVES: To investigate the factorial composition of the Trinity Amputation
      and Prosthesis Experience Scales (TAPES), a multidimensional assessment of
      adaptation to amputation and prosthesis, for use with individuals with acquired
      upper limb amputations. DESIGN: Cross-sectional survey of members of the British
      Limbless Ex-Service Men's Association. RESULTS: A total of 101 individuals (men,
      100; mean age, 73.8 yrs, SD 11.94) with acquired upper limb amputations (98
      traumatic cases) completed the TAPES. Principal components analyses with varimax
      rotation revealed four psychosocial subscales (general adjustment, social
      adjustment, optimal adjustment, and adjustment to limitation), four activity
      restriction subscales (restriction of lifestyle, social restriction, occupational
      restriction, and restriction of mobility), and a single prosthesis-satisfaction
      subscale. Each of these subscales had high internal reliability. CONCLUSIONS: The
      TAPES structure can be meaningfully represented in terms of nine internally
      consistent subscales. Additional research needs to be done on the TAPES for use
      with individuals with upper limb amputations. In particular studies of the
      scales, predictive validity is warranted.

PMID- 15973088
TI  - Optimum position of metatarsal pad in metatarsalgia for pressure relief.
AB  - OBJECTIVES: To determine the optimum position of a metatarsal (MT) pad to treat
      metatarsalgia. DESIGN: We used a sensing mat with 16 x 16 sensors, 4.4 x 4.4 mm
      each, to measure plantar pressure in ten metatarsalgia patients walking with an
      MT pad in various positions. Peak pressures of the MT head and MT pad were
      analyzed. RESULTS: Walking without MT pads, the peak pressure of the MT head was
      678 +/- 227 and 687 +/- 228 kPa in one proximal and one distal row of three
      sensors. Placement of the MT pad resulting in peak pressure two sensors proximal
      to the peak pressure of the MT head did not significantly reduce peak pressure on
      the MT head. In contrast, placement of the MT pad resulting in peak pressure just
      proximal to the peak pressures of the MT head reduced the proximal and distal
      peak pressures on the MT head to 427 +/- 97 and 431 +/- 92 kPa (P < 0.05).
      CONCLUSIONS: Optimum pressure reduction on the MT head is attained when the peak
      pressure generated by the MT pad is just proximal to the MT head.

PMID- 15973089
TI  - Efficacy of isokinetic exercise on joint position sense and muscle strength in
      patellofemoral pain syndrome.
AB  - OBJECTIVE: The objective of this study was to demonstrate the impairment of knee
      joint position sense in individuals with patellofemoral pain syndrome and
      investigate the effects of isokinetic exercise on knee joint position sense and
      muscle strength. DESIGN: A total of 24 male patients complaining of anterior knee
      pain caused by overexertion and 24 male healthy individuals without symptoms were
      included for this investigation. Isokinetic exercise protocol was carried out at
      angular velocities of 60 degrees/sec and 180 degrees/sec. These sessions were
      repeated three times per week and lasted for 6 wks. At the beginning and after 6
      wks of knee passive joint position sense, quadriceps and hamstring muscle
      strength and pain assessments were performed. RESULTS: After the isokinetic
      exercise, flexion peak torque (P < 0.05), extension peak torque (P < 0.01),
      flexion total work (P < 0.001), extension total work (P < 0.001), passive
      reproduction of knee joint position sense for 40 degrees of flexion (P < 0.05)
      and 50 degrees of extension (P < 0.01), and pain score (P < 0.001) improved
      significantly in the patellofemoral pain syndrome group. CONCLUSION: Isokinetic
      exercises have positive effects on passive position sense of knee joints,
      increasing the muscular strength and work capacity. These findings show that
      using the present isokinetic exercise in rehabilitation protocols of patients
      with patellofemoral pain syndrome not only improves the knee joint stabilization
      but also the proprioceptive acuity.

PMID- 15973090
TI  - Resolution of pronounced painless weakness arising from radiculopathy and disk
      extrusion.
AB  - In this retrospective, consecutive case series, we report the nonsurgical and
      rehabilitation outcomes of consecutive patients who presented with pronounced
      painless weakness arising from disk extrusion. Seven consecutive patients who
      chose physiatric care were followed clinically, and strength return was
      monitored. Each presented with predominantly painless radiculopathy, functionally
      significant strength loss, and radiographic evidence of disk extrusion or
      sequestration. Each patient participated in a targeted strengthening program, and
      in some cases, transforaminal injection therapy was employed. Each patient
      demonstrated an eventual full functional recovery. In most cases,
      electrodiagnostic studies were performed and included a needle examination of the
      affected limb and compound muscle action potentials from the most clinically
      relevant and weakened limb muscle. The electrodiagnostic findings and, in
      particular, the quantitative compound muscle action potential data seemed to
      correlate with the timing of motor recovery. Patients with predominantly painless
      and significant weakness arising from disk extrusion can demonstrate successful
      rehabilitation outcomes. Despite a relative absence of pain, such patients can
      present with a more rapidly reversible neurapraxic type of weakness. The more
      quantitative compound muscle action potential data obtained through
      electrodiagnostic studies may offer the treating physician an additional means of
      characterizing the type of neuronal injury at play and the likelihood and timing
      of strength return.

PMID- 15973091
TI  - Intradiscal electrothermal annuloplasty.
AB  - Low back pain is a common problem, and although the majority of cases of low back
      pain resolve, a subset of patients will continue to have intractable pain despite
      appropriate conservative treatments. Intradiscal electrothermal annuloplasty is a
      minimally invasive spinal procedure that has been proposed to treat provocation
      discography-proven internal disk disruption syndrome. The early uncontrolled and
      nonrandomized intradiscal electrothermal annuloplasty literature suggests it may
      provide some relief in a small proportion of strictly defined patients; however,
      more recent randomized, placebo-controlled trials have not substantiated these
      initial findings. This article will review the published literature, indications,
      contraindications, safety, and efficacy of the intradiscal electrothermal
      annuloplasty procedure for the treatment of chronic, intractable, axial back
      pain.

PMID- 15973092
TI  - Injections in patients with osteoarthritis and other musculoskeletal disorders:
      use of synthetic injection models for teaching physiatry residents.
AB  - This study examined whether resident injection skills could be enhanced using
      synthetic injection models. A total of 30 physiatry residents underwent written
      and injection-model pretesting and posttesting. After randomization into
      injection-model and control groups, the experimental group trained by watching an
      instructional videotape and by using models that gave visual feedback on
      injection accuracy, whereas the control group studied technical aspects of
      injections. Immediately after patient injections, a blinded attending graded
      residents on the required level of verbal or manual assistance. The experimental
      group performed significantly better during patient injections as per first
      injection data (i.e., the scores obtained from performing a procedure for the
      first time on each particular body region; P = 0.013), total injection data
      (i.e., the mean scores obtained from performing all procedures on each particular
      body region; P = 0.017), and postrotation practical testing (P < 0.007) but not
      for didactic knowledge (postrotation written testing; P < 0.039). Data analysis
      by body region showed significant benefit only for occasionally performed patient
      injection procedures. The benefit was most evident in less experienced residents.
      Injection-model accuracy testing correlated with actual patient injections, both
      for first injections into each major body region (r = 0.52, P = 0.005) and for
      all injections (r = 0.55, P = 0.003). Consideration should be given for
      incorporating injection-model training into residency education, especially for
      residents with less injection experience and for occasionally performed
      procedures. The overall correlation between model practical testing and
      subsequent patient injection performance suggests that models can measure
      injection competence.

PMID- 15973093
TI  - Effect of intradiscal electrothermal treatment with a short heating catheter and
      fibrin on discogenic low back pain.

PMID- 15973094
TI  - A randomized trial comparing axillary dissection to no axillary dissection in
      older patients with T1N0 breast cancer: results after 5 years of follow-up.
AB  - SUMMARY BACKGROUND DATA: Axillary dissection, an invasive procedure that may
      adversely affect quality of life, used to obtain prognostic information in breast
      cancer, is being supplanted by sentinel node biopsy. In older women with early
      breast cancer and no palpable axillary nodes, it may be safe to give no axillary
      treatment. We addressed this issue in a randomized trial comparing axillary
      dissection with no axillary dissection in older patients with T1N0 breast cancer.
      METHODS: From 1996 to 2000, 219 women, 65 to 80 years of age, with early breast
      cancer and clinically negative axillary nodes were randomized to conservative
      breast surgery with or without axillary dissection. Tamoxifen was prescribed to
      all patients for 5 years. The primary endpoints were axillary events in the no
      axillary dissection arm, comparison of overall mortality (by log rank test),
      breast cancer mortality, and breast events (by Gray test). RESULTS: Considering a
      follow-up of 60 months, there were no significant differences in overall or
      breast cancer mortality, or crude cumulative incidence of breast events, between
      the 2 groups. Only 2 patients in the no axillary dissection arm (8 and 40 months
      after surgery) developed overt axillary involvement during follow-up.
      CONCLUSIONS: Older patients with T1N0 breast cancer can be treated by
      conservative breast surgery and no axillary dissection without adversely
      affecting breast cancer mortality or overall survival. The very low cumulative
      incidence of axillary events suggests that even sentinel node biopsy is
      unnecessary in these patients. Axillary dissection should be reserved for the
      small proportion of patients who later develop overt axillary disease.

PMID- 15973096
TI  - Systematic appraisal of the role of metallic endobiliary stents in the treatment
      of benign bile duct stricture.
AB  - OBJECTIVE: To carry out a systematic appraisal of the current status of the use
      of metallic endobiliary stents in the treatment of benign biliary strictures.
      METHODS: A computerized search of the MEDLINE and EMBASE databases identified 37
      studies providing detailed clinical course data on outcome of metallic
      endobiliary stent placement in 400 patients. Pooled data were examined for
      etiology of stricture, indications for stent placement, procedure-related
      complications, and outcome with reference to stent patency. RESULTS: The median
      (range) number of patients per report was 8 (2-54) with a median recruitment
      period of 44 (9-126) months. The most frequent indications were postoperative
      biliary strictures in 123 (31%), stenosed biliary-enteric anastomoses in 79
      (20%), and biliary strictures following liver transplantation in 88 (22%). During
      a median follow up of 31 (1-111) months, 139 (35%) stents occluded, and there are
      little patency data beyond 2 years after deployment, with 99 (25%) known to be
      patent at 3 years from stent placement. CONCLUSIONS: These pooled data on 400
      patients constitute the largest collective report to date on the use of metallic
      endobiliary stents for benign biliary strictures. The results show a critical
      lack of data on long-term patency such that at the present time, metallic
      endobiliary stents should not be used for benign stricture in those patients with
      a predicted life expectancy greater than 2 years.

PMID- 15973097
TI  - Laparoscopic Roux-en-Y versus mini-gastric bypass for the treatment of morbid
      obesity: a prospective randomized controlled clinical trial.
AB  - OBJECTIVES: This prospective, randomized trial compared the safety and
      effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGBP) and laparoscopic
      mini-gastric bypass (LMGBP) in the treatment of morbid obesity. SUMMARY
      BACKGROUND DATA: LRYGBP has been the gold standard for the treatment of morbid
      obesity. While LMGBP has been reported to be a simple and effective treatment,
      data from a randomized trial are lacking. METHODS: Eighty patients who met the
      NIH criteria were recruited and randomized to receive either LRYGBP (n = 40) or
      LMGBP (n = 40). The minimum postoperative follow-up was 2 years (mean, 31.3
      months). Perioperative data were assessed. Late complication, excess weight loss,
      BMI, quality of life, and comorbidities were determined. Changes in quality of
      life were assessed using the Gastro-Intestinal Quality of Life Index (GIQLI).
      RESULTS: There was one conversion (2.5%) in the LRYGBP group. Operation time was
      shorter in LMGBP group (205 versus 148, P < 0.05). There was no mortality in each
      group. The operative morbidity rate was higher in the LRYGBP group (20% versus
      7.5%, P < 0.05). The late complications rate was the same in the 2 groups (7.5%)
      with no reoperation. The percentage of excess weight loss was 58.7% and 60.0% at
      1 and 2 years, respectively, in the LPYGBP group, and 64.9% and 64.4% in the
      LMGBP group. The residual excess weight <50% at 2 years postoperatively was
      achieved in 75% of patients in the LRYGBP group and 95% in the LMGBP group (P <
      0.05). A significant improvement of obesity-related clinical parameters and
      complete resolution of metabolic syndrome in both groups were noted. Both
      gastrointestinal quality of life increased significantly without any significant
      difference between the groups. CONCLUSION: Both LRYGBP and LMGBP are effective
      for morbid obesity with similar results for resolution of metabolic syndrome and
      improvement of quality of life. LMGBP is a simpler and safer procedure that has
      no disadvantage compared with LRYGBP at 2 years of follow-up.

PMID- 15973098
TI  - Stapled hemorrhoidopexy versus milligan-morgan hemorrhoidectomy: a prospective,
      randomized, multicenter trial with 2-year postoperative follow up.
AB  - PURPOSE: The purpose of this study was to compare the outcome of stapled
      hemorrhoidopexy (SH group) performed using a circular stapler with that of the
      Milligan-Morgan technique (MM group). The goals of the study were to evaluate the
      efficacy and reproducibility of stapled hemorrhoidopexy and define its place
      among conventional techniques. METHODS: A series of 134 patients were included at
      7 hospital centers. They were randomized according to a single-masked design and
      stratified by center (with balancing every 4 patients). Patients were clinically
      evaluated preoperatively and at 6 weeks, 1 year, and a minimum of 2 years after
      treatment. Patients completed a questionnaire before and 1 year after surgery to
      evaluate symptoms, function, and overall satisfaction. RESULTS: The mean follow
      up period was 2.21 years +/- 0.26 (1.89-3.07). Nine patients (7%) could not be
      monitored at 1 or 2 years, but 4 of these 9 nevertheless filled in the 1-year
      questionnaire. The patients in the SH group experienced less postoperative
      pain/discomfort as scored by pain during bowel movement (P < 0.001), total
      analgesic requirement over the first 3 days (according to the World Health
      Organization [WHO] class II analgesics [P = 0.002]; class III [P = 0.066]), and
      per-patient consumption frequency of class III analgesics (P = 0.089). A clear
      difference in morphine requirement became evident after 24 hours (P = 0.010).
      Hospital stay was significantly shorter in the SH group (SH 2.2 +/- 1.2 [0; 5.0]
      versus MM 3.1 +/- 1.7 [1; 8.0] P < 0.001). At 1 year, no differences in the
      resolution of symptoms were observed between the 2 groups, and over 2 years, the
      overall incidence of complications was the same, specifically fecaloma (P =
      0.003) in the MM group and external hemorrhoidal thrombosis (P = 0.006) in the SH
      group. Impaired sphincter function was observed at 1 year with no significant
      difference between the groups for urgency (12%), continence problems (10%), or
      tenesmus (3%). No patient needed a second procedure for recurrence within 2
      years, although partial residual prolapse was detected in 4 SH patients (7.5%)
      versus 1 MM patient (1.8%) (P = 0.194). CONCLUSION: Stapled hemorrhoidopexy
      causes significantly less postoperative pain. The technique is reproducible and
      can achieve comparable outcomes as those of the MM technique as long as the well
      described steps of the technique are followed. Like with conventional surgery,
      anorectal dysfunction can occur after stapled hemorrhoidopexy in some patients.
      Its effectiveness in relieving symptoms is equivalent to conventional surgery,
      and the number of hemorrhoidal prolapse recurrences at 2 years is not
      significantly different. Hemorroidopexy is applicable for treating reducible
      hemorrhoidal prolapse.

PMID- 15973099
TI  - Percutaneous ethanol injection versus surgical resection for the treatment of
      small hepatocellular carcinoma: a prospective study.
AB  - OBJECTIVE: To compare disease recurrence and survival among patients with small
      hepatocellular carcinoma after surgical resection or percutaneous ethanol
      injection therapy, 2 treatments that have not been evaluated with a prospective
      study. METHODS: A total of 76 patients were randomly assigned to 2 groups based
      on treatment; all had one or 2 tumors with diameter </=3 cm, with hepatitis
      without cirrhosis or Child class A or B cirrhosis without evident ascites or
      bleeding tendency. RESULTS: Follow-up ranged from 12 to 59 months. Among
      percutaneous injection patients, 18 had recurrence 1 to 37 months after treatment
      (true recurrence, 11; original safety margin inadequate, 3; limitation of imaging
      technology to detect tiny tumors, 4). Three injection therapy patients died of
      cancer 25, 37, and 57 months after treatment. For the surgical resection group,
      15 had recurrence 2 to 54 months after treatment (true recurrence, 12; limitation
      of imaging, 2; neck metastasis, 1). Five resection patients died of cancer at 11,
      20, 23, 26, and 52 months, respectively. By Cox regression model and Kaplan-Meier
      survival analysis, there is no statistical significance for recurrence and
      survival between treatment groups. However, tumor size larger than 2 cm and alpha
      fetoprotein over 200 ng/mL correlated with higher recurrence rate, and Child
      class B liver cirrhosis correlated with shorter survival. CONCLUSIONS:
      Percutaneous ethanol injection therapy appears to be as safe and effective as
      resection, and both treatments can be considered first-line options for small
      hepatocellular carcinoma.

PMID- 15973100
TI  - Restoration of normal distensive characteristics of the esophagogastric junction
      after fundoplication.
AB  - OBJECTIVE: To study the mechanical characteristics of the esophagogastric
      junction (EGJ) of postfundoplication patients and compare them with previously
      reported data on normal subjects and GERD patients. METHODS: Eight normal
      subjects, 9 GERD patients, and 8 fundoplication patients were studied with
      concurrent manometry, fluoroscopy, and stepwise controlled barostat distention of
      the EGJ. The minimal barostat pressure required to open the EGJ during the
      interswallow period was determined. Thereafter, barium swallows were imaged in 5
      mm Hg increments of intrabag pressure. EGJ diameter and length were measured at
      each pressure during deglutitive relaxation. RESULTS: EGJ opening diameter during
      deglutitive relaxation was on average 0.5 cm greater in GERD patients compared
      with normal subjects and fundoplication patients (P < 0.05). EGJ opening pressure
      and opening diameter were comparable between normal subjects and fundoplication
      patients; however, the EGJ length was 32% longer in fundoplication patients.
      CONCLUSIONS: Fundoplication restores distensibility of the EGJ to a level similar
      to normal subjects. Since trans-EGJ flow is related to EGJ length and EGJ
      diameter, these findings suggest that retrograde flow through the EGJ would be
      decreased by both a reduction in diameter and an increase in length of the EGJ.

PMID- 15973101
TI  - Barrett esophagus: risk factors for progression to dysplasia and adenocarcinoma.
AB  - OBJECTIVE: To evaluate risk factors for dysplasia and adenocarcinoma development
      in nondysplastic Barrett mucosa. SUMMARY BACKGROUND DATA: The risk for patients
      with Barrett esophagus to develop esophageal adenocarcinoma is low, and most
      patients undergoing surveillance will not develop malignancy. Identification of
      risk factors may allow for more rational surveillance programs in which patients
      are stratified according to their individual risk of progressing to dysplasia and
      invasive adenocarcinoma. METHODS: The development of dysplasia and esophageal
      adenocarcinoma was studied during long-term endoscopic and histologic
      surveillance in 140 patients with Barrett esophagus free from dysplasia. Risk
      factors for progression to dysplasia and adenocarcinoma were evaluated. RESULTS:
      Median follow-up was 5.8 years. Forty-four patients (31.4%) developed low-grade
      dysplasia and 7 patients (5%) developed high-grade dysplasia or esophageal
      adenocarcinoma. Dysplasia development was significantly less common after
      antireflux surgery compared with conventional medical therapy. Low-grade
      dysplasia (relative risk = 5.5; 95% confidence interval, 1.1-28.6) and long
      duration of reflux symptoms (relative risk = 1.3; 95% confidence interval, 1.2
      1.7) were independently associated with an increased risk of developing high
      grade dysplasia or esophageal adenocarcinoma. CONCLUSIONS: Successful antireflux
      surgery protects the Barrett mucosa from developing high-grade dysplasia and
      esophageal adenocarcinoma, possibly by better control of reflux of gastric
      contents. Low-grade dysplasia is the only clinically useful risk factor that
      permits stratification of the surveillance intervals according to the risk of the
      individual patient.

PMID- 15973102
TI  - Macrophage migration inhibitory factor stimulates angiogenic factor expression
      and correlates with differentiation and lymph node status in patients with
      esophageal squamous cell carcinoma.
AB  - OBJECTIVE: The objectives of this study were: 1) to examine the expression of
      macrophage migration inhibitory factor (MIF) in esophageal squamous cell
      carcinoma (ESCC); 2) to see if a relationship exists between MIF expression,
      clinicopathologic features, and long-term prognosis; and 3) to ascertain the
      possible biologic function of MIF in angiogenesis. SUMMARY BACKGROUND DATA: MIF
      has been linked to fundamental processes such as those controlling cell
      proliferation, cell survival, angiogenesis, and tumor progression. Its role in
      ESCC, and the correlation of MIF expression and tumor pathologic features in
      patients, has not been elucidated. METHODS: The expression of MIF in tumor and
      nontumor tissues was examined by immunohistochemical staining. Concentrations of
      MIF, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in
      patients' sera and in the supernatant of tumor cells culture were examined by
      ELISA. Correlations with clinicopathologic factors were made. RESULTS: In 72
      patients with ESCC, intracellular MIF was overexpressed in esophagectomy
      specimens. The expression of MIF correlated with both tumor differentiation and
      lymph node status. The median survival in the low-MIF expression group (<50%
      positively stained cancer cells on immunohistochemistry) and high expression
      group (>/=50% positively stained cancer cells) was 28.3 months and 15.8 months,
      respectively (P = 0.03). The 3-year survival rates for the 2 groups were 37.7%
      and 12.1%, respectively. MIF expression was related to microvessel density;
      increased MIF serum levels also correlated with higher serum levels of VEGF. In
      addition, in vitro MIF stimulation of esophageal cancer cell lines induced a dose
      dependent increase in VEGF and IL-8 secretion. CONCLUSIONS: These results
      demonstrate, for the first time, that human esophageal carcinomas express and
      secrete large amounts of MIF. Through its effects on VEGF and IL-8, MIF may serve
      as an autocrine factor in angiogenesis and thus play an important role in the
      pathogenesis of ESCC.

PMID- 15973103
TI  - Gastric carcinoids: biologic behavior and prognosis after differentiated
      treatment in relation to type.
AB  - OBJECTIVE: To analyze tumor biology and the outcome of differentiated treatment
      in relation to tumor subtype in patients with gastric carcinoid. BACKGROUND:
      Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated
      with atrophic gastritis, type 2 associated with gastrinoma, type 3 without
      predisposing conditions) and miscellaneous types (type 4). The biologic behavior
      and prognosis vary considerably in relation to type. METHODS: A total of 65
      patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were
      included. Management recommendations were issued for newly diagnosed cases, that
      is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including
      antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4
      carcinoids. RESULTS: Infiltration beyond the submucosa occurred in 9 of 51 type
      1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51
      type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph
      nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of
      the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated
      with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7
      underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical
      tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients
      with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and
      73.9% for type 1 (not different from the general population), but only 33.3% and
      22.2% for type 4 carcinoids. CONCLUSION: Subtyping of gastric carcinoids is
      helpful in the prediction of malignant potential and long-term survival and is a
      guide to management. Long-term survival did not differ from that of the general
      population regarding type 1 carcinoids but was poor regarding type 4 carcinoids.

PMID- 15973104
TI  - The modern abdominoperineal excision: the next challenge after total mesorectal
      excision.
AB  - OBJECTIVES: Examine the cause of local recurrence (LR) and patient survival (S)
      following abdominoperineal resection (APR) and anterior resection (AR) for rectal
      carcinoma and the effect of introduction of total mesorectal excision (TME) on
      APR. METHODS: A total of 608 patients underwent surgery for rectal cancer in
      Leeds from 1986 to 1997. CRM status and follow-up data of local recurrence and
      patient survival were available for 561 patients, of whom 190 underwent APR
      (32.4%) and 371 AR (63.3%). Also, a retrospective study of pathologic images of
      93 specimens of rectal carcinoma. RESULTS: Patients undergoing APR had a higher
      LR and lower survival (LR, 22.3% versus 13.5%, P = 0.002; S, 52.3% versus 65.8%,
      P = 0.003) than AR. LR free rates were lower in the APR group and cancer specific
      survival was lowered (LR, 66% versus 77%, log rank P = 0.03; S, 48% versus 59%,
      log rank P = 0.02). Morphometry: total area of surgically removed tissue outside
      the muscularis propria was smaller in APR specimens (n = 27) than AR specimens (n
      = 66) (P < 0.0001). Linear dimensions of transverse slices of tissue containing
      tumor, median posterior, and lateral measurements were smaller (P < 0.05) in the
      APR than the AR group. APR specimens with histologically positive CRM (n = 11)
      had a smaller area of tissue outside the muscularis propria (P = 0.04) compared
      with the CRM-negative APR specimens (n = 16). Incidence of CRM involvement in the
      APR group (41%) was higher than in the AR group (12%) (P = 0.006) in the 1997 to
      2000 cohort. Similar results (36% and 22%) were found in the 1986 to 1997 cohort
      (P = 0.002). CONCLUSIONS: Patients treated by APR have a higher rate of CRM
      involvement, a higher LR, and poorer prognosis than AR. The frequency of CRM
      involvement for APR has not diminished with TME. CRM involvement in the APR
      specimens is related to the removal of less tissue at the level of the tumor in
      an APR. Where possible, a more radical operation should be considered for all low
      rectal cancer tumors.

PMID- 15973105
TI  - Evaluation of the learning curve in laparoscopic colorectal surgery: comparison
      of right-sided and left-sided resections.
AB  - OBJECTIVE: To provide a multidimensional analysis of the learning curve in major
      laparoscopic colonic and rectal surgery and compare outcomes between right-sided
      versus left-sided resections. SUMMARY BACKGROUND DATA: The laparoscopic learning
      curve is known to vary between surgeons, may be influenced by the patient
      selection and operative complexity, and requires appropriate case-mix adjustment.
      METHODS: This is a descriptive single-center study using routinely collected
      clinical data from 900 patients undergoing laparoscopic surgery between November
      1991 and April 2003. Outcome measures included operation time, conversion rate
      (CR), and readmission and postoperative complication rates. Multifactorial
      logistic regression analysis was used to identify patient-, surgeon-, and
      procedure-related factors associated with conversion of laparoscopic to open
      surgery. A risk-adjusted Cumulative Sum (CUSUM) model was used for evaluating the
      learning curve for right and left-sided resections. RESULTS: The conversion rate
      for right-sided colonic resections was 8.1% (n = 457) compared with 15.3% for
      left-sided colorectal resections (n = 443). Independent predictors of conversion
      of laparoscopic to open surgery were the body mass index (BMI) (odds ratio [OR] =
      1.07 per unit increase), ASA grade (OR = 1.63 per unit increase), type of
      resection (left colorectal versus right colonic procedures, OR = 1.5), presence
      of intra-abdominal abscess (OR = 5.0) or enteric fistula (OR = 4.6), and
      surgeon's experience (OR 0.9 per 10 additional cases performed). Having adjusted
      for case-mix, the CUSUM analysis demonstrated a learning curve of 55 cases for
      right-sided colonic resections versus 62 cases for left-sided resections. Median
      operative time declined with operative experience (P<0.001). Readmission rates
      and postoperative complications remained unchanged throughout the series and were
      not dependent on operative experience. CONCLUSIONS: Conversion rates for
      laparoscopic colectomy are dependent on a multitude of factors that require
      appropriate adjustment including the learning curve (operative experience) for
      individual surgeons. The laparoscopic model described can be used as the basis
      for performance monitoring between or within institutions.

PMID- 15973106
TI  - Clinicopathologic analysis of early ampullary cancers with a focus on the
      feasibility of ampullectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether ampullectomy can
      substitute for pancreatoduodenectomy (PD) in early ampullary cancer by
      clinicopathologic study. SUMMARY BACKGROUND DATA: Although ampullectomy has been
      attempted in early ampullary cancer (pTis, pT1), the indication and extent of
      resection have not been established. METHODS: Of 201 patients who had undergone
      PD for ampullary cancer between 1986 and 2002, 67 patients with a histologic
      diagnosis of pTis (n = 5) or pT1 (n = 62) cancer were analyzed retrospectively.
      Pathologic PD specimens were reviewed to analyze the cancer spread pattern, and
      medical records were reviewed for clinical outcomes. RESULTS: The 5-year survival
      rate of the 66 patients with early ampullary cancer (excluding one mortality) was
      83.7%. Recurrence was confirmed in 12 patients (18.2%) and all died because of
      the recurrence. Pathologic review showed that 22 patients (32.8%) had at least
      one risk factor for failure after ampullectomy: lymph node metastasis (n = 6,
      9.0%), perineural invasion (n = 1), or mucosal tumor infiltration along the CBD
      or P-duct (n = 15, 22.4%). Mean lengths of invasion into the CBD or the P-duct
      beyond the sphincter of Oddi were 7.7 mm (range, 1-25 mm) or 6.3 mm (range, 2-18
      mm), respectively. Moreover, these risk factors were not correlated with tumor
      size, histologic grade, or the gross morphology of the primary tumor, although
      pTis cancer or pT1 cancer sized 1.0 cm or less was found to be least associated
      with risk factors. CONCLUSIONS: Ampullectomy for early ampullary cancer should
      not be considered an alternative operation to PD because of the high possibility
      of recurrence. PD should be preferably performed for adequate radical resection,
      even in early ampullary cancer, and ampullectomy should be reserved for those who
      have pTis or pT1 cancer sized 1.0 cm or less with high operative risk.

PMID- 15973107
TI  - Full-dose intraoperative radiotherapy with electrons during breast-conserving
      surgery: experience with 590 cases.
AB  - BACKGROUND: Previous studies show that local recurrences after breast-conserving
      treatment occur in the site of the primary tumor. The need for postoperative
      radiotherapy on the whole breast is challenged in favor of radiotherapy limited
      to the area of the breast at high risk of recurrence. The new mobile linear
      accelerators easily moved close to the operating table to allow the full-dose
      irradiation during surgery. PATIENTS AND METHODS: From July 1999 to December
      2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5
      cm received wide resection of the breast followed by intraoperative radiotherapy
      with electrons (ELIOT). Most patients received 21 Gy intraoperatively,
      biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were
      evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to
      look for early, intermediate, late complications, and other events. RESULTS:
      After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19
      patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which
      resolved within 24 months. Three patients (0.5%) developed local recurrences, 3
      patients ipsilateral carcinomas in other quadrants and other 5 patients
      contralateral breast carcinoma. One patient (0.2%) died of distant metastases.
      CONCLUSIONS: ELIOT is a safe method for treating conservatively operated breasts,
      avoids the long period of postoperative radiotherapy, and reduces drastically the
      cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs.
      Results on short-term and middle-term toxicity up to 5 years of follow-up are
      good. Data on local control are encouraging.

PMID- 15973108
TI  - Preoperative antibiotics and mortality in the elderly.
AB  - OBJECTIVE AND BACKGROUND: It is generally thought that the use of preoperative
      antibiotics reduces the risk of postoperative infection, yet few studies have
      described the association between preoperative antibiotics and the risk of dying.
      The objective of this study was to determine whether preoperative antibiotics are
      associated with a reduced risk of death. METHODS: We performed a multivariate
      matched, population-based, case-control study of death following surgery on 1362
      Pennsylvania Medicare patients between 65 and 85 years of age undergoing general
      and orthopedic surgery. Cases (681 deaths within 60 days from hospital admission)
      were randomly selected throughout Pennsylvania using claims from 1995 and 1996.
      Models were developed to scan Medicare claims, looking for controls who did not
      die and who were the closest matches to the previously selected cases based on
      preoperative characteristics. Cases and their controls were identified, and
      charts were abstracted to define antibiotic use and obtain baseline severity
      adjustment data. RESULTS: For general surgery, the odds of dying within 60 days
      were less than half in those treated with preoperative antibiotics within 2 hours
      of incision as compared with those without such treatment: (odds ratio = 0.44;
      95% confidence interval, 0.32-0.60), P < 0.0001). For orthopedic surgery, no
      significant mortality reduction was observed (OR = 0.85; 95% confidence interval,
      0.54-1.32; P < 0.464). INTERPRETATION: Preoperative antibiotics are associated
      with a substantially lower 60-day mortality rate in elderly patients undergoing
      general surgery. In patients who appear to be comparable, the risk of death was
      half as large among those who received preoperative antibiotics.

PMID- 15973110
TI  - Regeneration of the rat neonatal intestine in transplantation.
AB  - OBJECTIVE: Based on development of stem cell technology, newborn tissue, even
      undergoing cryopreservation, possesses promising potential as a donor source in
      the field of organ transplantation. However, the precise regeneration processes
      remains unclear. This study was designed to investigate the regenerative
      potential of newborn intestine with or without cryopreservation in the
      transplantation. METHODS: Newborn rat intestines with or without cryopreservation
      were transplanted subcutaneously into the syngeneic host, and specimens were
      evaluated by histology, multiple immunostaining, and comprehensive gene
      expression analysis. RESULTS: We determined that newborn rat intestine possessed
      regenerative potential in the syngeneic host even after cryopreservation, where
      angiogenesis was induced early in the submucosa with subsequent maturation in the
      crypts. Furthermore, newborn intestinal graft could facilitate the survival of
      maturation-incompetent 10-day-old graft that lacked regenerating activity (P <
      0.01, n = 13). Tissue aggregates from the maturation-incompetent graft underwent
      reconstitution of their histologic configuration in the presence of newborn
      intestinal aggregates. Comprehensive gene expression analysis showed that 37
      genes were preferentially up-regulated, while 19 genes were down-regulated in the
      regenerating 10-day-old graft (supported by the newborn graft). CONCLUSIONS:
      Regeneration of newborn intestine is implicated in neo-angiogenesis in the host,
      and the newborn intestinal graft is capable of mediating the survival of the
      maturation-incompetent 10-day-old graft. Notwithstanding ethical and legal
      limitations in the clinic, these results may provide new insights into the
      regenerative role of newborn grafts.

PMID- 15973109
TI  - Mechanisms responsible for vascular hyporesponsiveness to adrenomedullin after
      hemorrhage: the central role of adrenomedullin binding protein-1.
AB  - OBJECTIVE: Irreversible hypovolemia remains a major clinical problem. Preliminary
      studies indicate that administration of adrenomedullin and adrenomedullin binding
      protein-1 in combination (AM/AMBP-1) after hemorrhage, improves cardiovascular
      function despite the increased levels of AM. Our aim was to determine whether
      vascular responsiveness to AM is reduced after hemorrhage and, if so, to
      elucidate the possible mechanism responsible for such hyporesponsiveness.
      METHODS: Male rats were bled to and maintained at a mean arterial pressure of 40
      mm Hg for 90 minutes. The animals were then resuscitated with 4 times the volume
      of shed blood with lactated Ringer's solution over 60 minutes. At 1.5 hours
      postresuscitation, vascular responses to AM and AMBP-1, plasma levels of AM and
      AMBP-1, AMBP-1 and AM receptor gene expression were measured. In additional
      animals, AM and AMBP-1 were administered intravenously at 15 minutes after
      resuscitation over 45 minutes. Serum levels of liver enzymes, lactate,
      creatinine, TNF-alpha, IL-6, and IL-10 were measured at 1.5 hours
      postresuscitation. RESULTS: AM-induced vascular relaxation decreased
      significantly after hemorrhage and resuscitation, which was markedly improved by
      AMBP-1. However, AM receptor gene expression did not change under such
      conditions. Hemorrhage-induced AM hyporesponsiveness was accompanied by the
      decreased expression and release of AMBP-1. Moreover, AM/AMBP-1 treatment down
      regulated TNF-alpha and IL-6, up-regulated IL-10, and attenuated organ injury.
      CONCLUSIONS: The decreased AMBP-1 levels rather than alterations in AM receptors
      are responsible for producing AM hyporesponsiveness after hemorrhage. Thus,
      administration of AMBP-1 in combination with AM can be useful to reduce organ
      injury after severe hypovolemia.

PMID- 15973111
TI  - Effects of 10 minutes of ischemic preconditioning of the cadaveric liver on the
      graft's preservation and function: the ying and the yang.
AB  - SUMMARY BACKGROUND DATA: Although extensively studied in animal models, ischemic
      preconditioning has not yet been studied in clinical transplantation. OBJECTIVE:
      To compare the results of cadaveric liver transplantation with and without
      ischemic liver preconditioning in the donor. PATIENTS AND METHODS: Alternate
      patients were transplanted with liver grafts that had (n = 46, GroupPrecond) or
      had not (n = 45, GroupControl) been subjected to ischemic preconditioning. Liver
      ischemia-reperfusion injury, liver and kidney function, morbidity, and in
      hospital mortality rates were compared in the 2 groups. Initial poor function was
      defined as a minimal prothrombin time within 10 days of transplantation <30% of
      normal and/or bilirubin >200 micromol/L. RESULTS: The postoperative peaks of ASAT
      (IU/L) and ALAT (IU/L) were significantly lower in GroupPrecond (556 +/- 968 and
      461+/-495, respectively) than in the GroupControl (1073 +/- 1112 and 997+/-1071,
      respectively). The rate of technical morbidity and the incidence of acute
      rejection were similar in both groups. Initial poor function was significantly
      more frequent in the GroupPrecond (10 of 46 cases) than in the GroupControl (3 of
      45 cases). Hospital mortality rates were similar in the 2 groups. In multivariate
      analysis, body mass index of the donor, graft steatosis, and ischemic
      preconditioning were significantly predictive of the posttransplant peak of ASAT.
      In univariate analysis, only preconditioning was significantly associated with
      initial poor function. CONCLUSIONS: Compared with standard orthotopic liver
      transplant, ischemic preconditioning of the liver graft in the donor is
      associated with better tolerance to ischemia. However, this is at the price of
      decreased early function. Until further studies are available, the clinical value
      of preconditioning liver grafts remains uncertain.

PMID- 15973113
TI  - Accelerated partial breast irradiation after conservative surgery for breast
      cancer.

PMID- 15973112
TI  - Prevention of intra-abdominal adhesions using the antiangiogenic COX-2 inhibitor
      celecoxib.
AB  - OBJECTIVE: To determine the effects of COX-2 specific inhibitors on postoperative
      adhesion formation. SUMMARY AND BACKGROUND DATA: Intra-abdominal adhesions are
      the major cause of intestinal obstruction and secondary infertility after
      surgical procedures. Because adhesion synthesis requires angiogenesis, and
      cyclooxygenase-2 enzyme (COX-2) inhibitors have antiendothelial activity, we
      tested COX-2 inhibitors in a murine model of intra-abdominal adhesion formation.
      METHODS: A silicone patch was secured to the lateral abdominal wall of groups of
      C57BL/6 mice, followed by cecal abrasion to promote adhesion formation. Beginning
      on the day of surgery, mice were treated with the selective COX-2 agents,
      celecoxib or rofecoxib, and the nonspecific COX inhibitors, aspirin, naproxen,
      ibuprofen, or indomethacin. Animals were treated for 10 days and killed. A second
      group (celecoxib, rofecoxib, aspirin) was treated for 10 days and observed for an
      additional 25 days. After treatment, intra-abdominal adhesions were scored using
      a standard method. The patch was subjected to immunohistochemistry with the
      endothelial-specific marker, CD31. RESULTS: Animals treated with selective and
      nonselective COX-2 inhibitors, except aspirin, had significantly fewer adhesions
      than control animals. Celecoxib produced a maximal reduction in adhesion
      formation compared with rofecoxib and the nonselective COX-2 inhibitors at 10
      days. After 25 days, celecoxib and rofecoxib, but not aspirin, had fewer
      adhesions than control mice. Adhesions from mice treated with celecoxib had
      reduced microvessel density compared with rofecoxib, the nonselective COX
      inhibitors, and control animals. CONCLUSIONS: Selective COX-2 inhibitors, in
      particular celecoxib, provide durable inhibition of intra-abdominal adhesions
      through an antiangiogenic mechanism.

PMID- 15973115
TI  - Efficacy and safety of mesalamine 1 g HS versus 500 mg BID suppositories in mild
      to moderate ulcerative proctitis: a multicenter randomized study.
AB  - BACKGROUND: Ulcerative proctitis (UP) usually presents as fresh rectal bleeding.
      Successful treatment using topical mesalamine 5-aminosalicyclic acid (5-ASA) 500
      mg BID suppository led to developing a once-a-day formulation that could
      contribute to better acceptability and ease of use by patients. The objective of
      this randomized trial, conducted in 18 centers, was to compare efficacy of 2
      modes of treatment with 5-ASA suppositories. METHODS: Ninety-nine patients with
      mild or moderate UP limited to 15 cm of the anal margin, evidenced by a disease
      activity index (DAI) between 4 and 11, were randomized to 5-ASA 500 mg
      suppository (Canasa; Axcan Pharma) BID or 1 g at bedtime (HS) for 6 weeks. The
      study used a noninferiority hypothesis based on the mean difference in DAI values
      after 6 weeks of treatment on an intent-to-treat basis using analysis of
      covariance. DAI was derived from a composite of the measures of stool frequency,
      rectal bleeding, mucosal visualization at endoscopy, and general well being.
      RESULTS: There was no difference between groups at baseline for demographic and
      clinical parameters. Mean DAIs fell from 6.6 +/- 1.5 (SD) to 1.6 +/- 2.3 in the
      500 mg BID group (n = 48) and from 6.1 +/- 1.5 to 1.3 +/- 2.2 in the 1 g HS group
      (n = 39). There was no significant difference (P = 0.74) in mean DAI at week 6
      between the 2 groups. Both groups showed a significant reduction (P < 0.0001) in
      DAI over the course of the 6 weeks. Both formulations showed effectiveness in
      reducing each individual component of the DAI. There was no significant
      difference between treatments in adverse events, and both groups had an overall
      drug compliance of greater than 95%. CONCLUSION: This study showed that 1 g HS
      and 500 mg BID mesalamine suppository treatments of UP patients were equivalent
      in all facets of efficacy, safety, and compliance in a 6-week trial.

PMID- 15973116
TI  - Comparative phenotypic and CARD15 mutational analysis among African American,
      Hispanic, and White children with Crohn's disease.
AB  - BACKGROUND: Despite a large body of literature on the subject of Crohn's disease
      (CD), very little information is available on racial/ethnic differences related
      to disease presentation, clinical course, and genetics. The first identified CD
      susceptibility gene, CARD15, seems to be present in up to 40% of white children
      with CD. However, the frequency of this gene among patients with CD of other
      racial/ethnic groups in the United States is not known. METHODS: We conducted a
      multicenter study on African American and Hispanic children with CD to describe
      the phenotypic and genotypic (CARD15) features in comparison with white children
      with CD. We also analyzed the frequency of CARD15 mutations in large control
      samples from white, African American, and Hispanic children. RESULTS: The disease
      location and behavior were similar among all 3 groups, with inflammatory behavior
      and the ileocolonic location being the most frequent phenotype. However,
      significantly lower frequencies of CARD15 mutations were seen in African American
      (P < 0.0001) and Hispanic (P < 0.0001) children with CD compared with white
      children with CD. This lower CARD15 frequency among African American patients
      with CD was also mirrored in the general population. CONCLUSIONS: Phenotypic
      features of CD are similar among African American and Hispanic children compared
      with white children. CARD15 mutations are not increased among African American
      and Hispanic children with CD. CARD15 mutational frequencies among African
      American and Hispanic children within the general population are lower compared
      with white children within the general population. Future genetics studies will
      be required to determine the relationships between genotype and CD phenotype in
      various ethnic and racial groups.

PMID- 15973117
TI  - Ileal involvement is age dependent in pediatric Crohn's disease.
AB  - BACKGROUND: Lymphoid follicles (LFs) have been suggested to play a role at the
      early stage of Crohn's disease (CD) lesions. In the small bowel, LFs are grouped,
      forming Peyer's patches, which develop early in fetal life, grow in size and
      number until puberty, and undergo involution. In contrast, colonic LFs are
      isolated and undergo little change during life. As a result, if LFs play a role
      in the occurrence of CD lesions, the distribution of ileal and colonic lesions is
      expected to be altered in small children. METHODS: Medical records of 2
      independent French (n = 136) and Swedish (n = 55) cohorts of consecutive
      pediatric CD were reviewed. Disease sites and age of onset were recorded, and the
      age-dependent probability to develop ileal lesions was computed. The CARD15/NOD2
      genotype was also analyzed when available (n = 99). RESULTS: The curves of
      disease occurrence were significantly different in case of CD with or without
      ileal lesions (P < 0.0001). At the age of 8 years, the probability (95%
      confidence interval) of small bowel involvement was 0.19 (0.07-0.39). It
      increased until 16 years of age to 0.61 (0.54-0.68). It was slightly higher in
      patients carrying 1 or more CARD15/NOD2 mutations [0.75 (0.55-0.89)] than in wild
      type patients [0.46 (0.34-0.58)]. CARD15 mutations also influenced the age of
      onset of ileal disease (P < 0.02). CONCLUSIONS: In children, ileal CD lesions are
      delayed compared with colonic lesions. This observation is in agreement with the
      previously proposed hypothesis of a pathophysiological role of Peyer's patches in
      ileal CD. The rarity of small bowel lesions should be a warning to be cautious
      when classifying chronic colitis in small children.

PMID- 15973118
TI  - The role of Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and
      CARD15/NOD2 mutations in the susceptibility and phenotype of Crohn's disease.
AB  - BACKGROUND: We investigated the influence of 2 common Toll-like receptor 4 (TLR4)
      polymorphisms on susceptibility and disease characteristics of Crohn's disease
      (CD). METHODS: Genomic DNA from 204 patients with CD and 199 unrelated controls
      was analyzed for the presence of 2 single nucleotide polymorphisms in the TLR4
      gene, resulting in the amino acid substitutions Asp299Gly and Thr399Ile. In
      addition, the carrier status for the 3 common CD-associated CARD15/NOD2 gene
      mutations, Arg702Trp, Gly908Arg, and 1007fs, was determined. The frequency of the
      different genotypes was compared, and a detailed genotype-phenotype correlation
      was performed. RESULTS: An almost 2-fold increase in the frequency of the TLR4
      Asp299Gly phenotype was observed in patients with CD (14.2%) compared with
      healthy controls (7.5%, P = 0.038, odds ratio = 2.03). The prevalence of a
      stricturing phenotype was increased in patients heterozygous for 1 of the TLR4
      polymorphisms studied (Asp299Gly, 34.5%; Thr399Ile, 36.7%) compared with patients
      with wild-type TLR4 (17.1% and 16.7%; P = 0.04 and 0.02, respectively). The
      presence of the Asp299Gly polymorphism in the absence of CARD15/NOD2 mutations
      was a particularly strong predictor of the stricturing disease phenotype that was
      present in 47.4% of the patients with Asp299Gly+/NOD2- compared with 10.1% of the
      patients with the Asp299Gly-/NOD2+ status (P = 0.0009; P = 0.0004 for
      Thr399Ile+/NOD2- versus Thr399Ile-/NOD2+). In contrast, there was a trend toward
      a higher prevalence of the penetrating phenotype in the TLR4-/NOD2+ group (71.6%)
      compared with the TLR4+/NOD2- group (47.4%, P = 0.059). CONCLUSIONS: The TLR4
      Asp299Gly polymorphism is a risk factor for CD. TLR4 and CARD15/NOD2 mutations
      may contribute to distinct disease phenotypes.

PMID- 15973119
TI  - CTLA-4 gene polymorphisms in Chinese patients with ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) is characterized by chronic inflammation of
      the colon and rectum as a result of an exaggerated T-cell response. Cytotoxic T
      lymphocyte-associated antigen 4 (CTLA-4) is a T cell-restricted surface molecule
      induced with TCR or CD28 activation. There is evidence for genetic involvement of
      CTLA-4 in several autoimmune diseases, with the focus on the possible role of
      genetic variation of the CTLA-4 locus. The aim of this study was to investigate
      CTLA-4 gene polymorphisms in patients with UC in a Chinese population with Han
      nationality. METHODS: The C-318T polymorphism in the promoter region and A+49G
      polymorphism in exon 1 of the CTLA-4 gene were studied by a polymerase chain
      reaction-sequence-specific primer method. We studied 82 unrelated patients with
      UC and 204 healthy controls in a Chinese population with Han nationality.
      RESULTS: The frequency of the haplotype 2,3 (-318C+49G/-318T+49A) was 26% in
      patients with UC and 41% in healthy controls (Fisher exact test P = 0.0147, odds
      ratio = 0.4918, 95% confidence interval: 0.2784 - 0.8688), but this significance
      disappeared when Bonferoni correction was applied. No other significant
      differences in the distribution of allele and genotype frequencies were observed
      between C-318T and A+49G gene polymorphisms and UC in the Chinese Han population.
      CONCLUSION: The C-318T and A+49G polymorphisms of the CTLA-4 gene were not
      associated with UC in Chinese Han patients.

PMID- 15973120
TI  - Intra- and interobserver variation in the use of the Vienna classification of
      Crohn's disease.
AB  - BACKGROUND: Crohn's disease is a heterogeneous disease, and several
      classification systems have been developed to classify the patients in more
      homogeneous groups. Our aim was to assess the intra- and interobserver variation
      when classifying patients according to the widely used Vifenna classification.
      METHODS: Ten randomly selected Crohn's disease cases were presented to 11 Danish
      gastroenterologists with a special interest in inflammatory bowel diseases.
      Clinical details, together with endoscopic, radiologic, and pathologic reports,
      were presented to the participants as a PowerPoint slide show, sent by e-mail
      with a data collection form. The experts were asked to classify the cases
      according to the Vienna classification and to evaluate intraobserver variation;
      the participants classified the patients 3 times. The strength of agreement was
      calculated using kappa statistics. RESULTS: Classification of the patients
      according to age gave a kappa value of 1.00. The intraobserver kappa value was
      good, with an average kappa value of 0.75 (range, 0.42-0.86) for location and
      0.77 (range, 0.53-1.00) for behavior. The mean overall interobserver kappa value
      was 0.64 (range, 0.12-1.00), which improved slightly between the first and third
      rounds. When classifying according to location and behavior, most patients were
      classified in 2 or 3 different ways, and in no patients was there full agreement
      among the observers for both location and behavior. CONCLUSIONS: In this study,
      we found an overall good interobserver agreement when using the Vienna
      classification, although when looking at individual cases, there was some
      disagreement.

PMID- 15973121
TI  - High prevalence of celiac disease among patients affected by Crohn's disease.
AB  - BACKGROUND: Recent literature has shown a correlation between Crohn's disease
      (CD) and celiac disease, but a prospective study has not been performed. Our aim
      was to evaluate the prevalence of celiac disease in a consecutive series of
      patients affected by CD, in whom the disease was diagnosed for the first time.
      METHODS: From January to December 2004, we diagnosed 27 patients affected by CD
      (13 men and 14 women; mean age, 32.3 yrs; range, 16-69 yrs). In all patients, we
      performed antigliadin, antiendomysium, and antitransglutaminase antibody tests,
      and the sorbitol H2 breath test evaluation. In case of antibodies and/or sorbitol
      positivity, esophagogastroduodenoscopy was performed for a small bowel biopsy.
      RESULTS: Antigliadin, antiendomysium, and antitransglutaminase antibody tests
      were positive in 8/27 (29.63%), 4/27 (14.81%), and 5/27 (18.52%) patients,
      respectively, whereas the sorbitol H2 breath test was positive in 11/27 (40.74%)
      patients: all of them underwent esophagogastroduodenoscopy. Nine of 11 patients
      showed signs of duodenal endoscopic damage, and 5/9 (55.55%) showed histologic
      features of celiac disease (18.52% of overall CD population studied): 2 showed
      Marsh IIIc lesions (1 patient affected by ileal CD and 1 affected by ileo-colonic
      CD), 2 showed Marsh IIIb lesions (all of them affected by ileo-colonic CD), 1
      showed a Marsh IIIa lesion (1 patient affected by colonic CD). CONCLUSIONS:
      Prevalence of celiac disease seems to be high among patients affected by CD, and
      this finding should be kept in mind at the time of the first diagnosis of CD; a
      gluten-free diet should be promptly started.

PMID- 15973122
TI  - Hyperresponsiveness of the mucosal barrier in Crohn's disease is not tumor
      necrosis factor-dependent.
AB  - BACKGROUND: Crohn's disease (CD) is associated with gut barrier dysfunction.
      Besides the baseline barrier defect, a subgroup of patients also expresses an
      intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs.
      We studied whether reducing inflammation and restoring gut barrier dysfunction
      with anti-tumor necrosis factor (TNF) antibody treatment also antagonizes the
      permeability increase by oral nonsteroidal anti-inflammatory drug intake in
      patients with CD. METHODS: Thirty-one healthy control subjects and 25 patients
      with active CD were studied. The 31 controls performed intestinal permeability
      testing for Cr-EDTA before (baseline) and after oral intake of indomethacin (50 +
      75 mg). Twenty-five patients carried out a baseline and indomethacin-mediated
      permeability test before infliximab infusion. The patients repeated either the
      indomethacin test (12/25) or baseline and indomethacin tests (13/25), 1 month
      after this treatment. Intestinal permeability was studied by measurement of
      urinary excretion of Cr-EDTA after oral intake. RESULTS: Increased whole gut
      permeation before treatment (3.16%; interquartile range [IQR], 2.92-5.72) was
      restored to normal values (2.47%; IQR, 1.97-2.78) by anti-TNF treatment.
      Indomethacin increased whole gut permeability significantly more in patients with
      CD (before anti-TNF: 6.50%; IQR, 4.84-10.38; after anti-TNF: 5.50%; IQR, 3.97
      10.09) compared with the healthy subjects (4.66%; IQR, 3.51-5.64). Eleven of 25
      patients (44%) had an abnormal whole gut permeability response to indomethacin
      before anti-TNF, and 9 of them remained hyperresponsive after infusion, despite
      clinical remission. CONCLUSIONS: Although anti-TNF treatment suppresses
      inflammation and restores gut barrier function in patients with CD, it does not
      antagonize the barrier hyperresponsiveness to indomethacin. These data support
      the notion of an underlying intestinal mucosal barrier hyperresponsiveness in a
      subset of patients with CD, independent of inflammation.

PMID- 15973123
TI  - cDNA array analysis of cytokines, chemokines, and receptors involved in the
      development of TNBS-induced colitis: homeostatic role of VIP.
AB  - Crohn's disease (CD) is a chronic inflammatory pathology of the intestine,
      characterized by diarrhea and weight loss. A healing effect of vasoactive
      intestinal peptide (VIP) in the murine model of CD based on 2,4,6-trinitrobencene
      sulfonic acid (TNBS) administration has been previously shown. The aim of this
      work was to analyze the expression of several mediators related to the
      inflammatory cascade in colitic and VIP-treated animals. With this aim, mice
      received either only TNBS or TNBS and VIP treatment on alternate days. cDNA
      microarray analysis and real-time polymerase chain reaction were performed on
      total mRNA from colon to study the expression of a battery of proinflammatory
      molecules such as the enzyme COX-2, the chemokines CX3CL1, CXCL12, CXCL13,
      CXCL14, CCR5, and CXCR2, and the cytokines interleukin (IL)-1beta, IL-12, IL-18,
      IL-10, interferon-gamma, and IL-4. TNBS administration induced the expression of
      all the proinflammatory mediators studied, whereas VIP treatment reduced their
      levels, increasing the anti-inflammatory IL-10 and the TH2 cytokine IL-4,
      explaining its beneficial action through inhibition of the inflammatory/TH1
      response. These data describe not only the relation of several proinflammatory
      mediators to the development of TNBS colitis, reporting their time-course, but
      also show the beneficial action of VIP in this model through complete blockage of
      the inflammatory cascade and recovery of the colon homeostasis, providing a
      potential new alternative for CD therapy.

PMID- 15973124
TI  - Methods to avoid infections in patients with inflammatory bowel disease.
AB  - Infections have been reported in patients with inflammatory bowel disease (IBD),
      especially in association with anti-inflammatory and immunomodulatory medications
      used to treat IBD. Unfortunately, there is a dearth of information on infectious
      complication risk in patients with IBD. This review describes infectious
      complications reported in patients with IBD and provides a framework for future
      studies to assess potential risk factors and incidence for infection.
      Recommendations are also provided for prevention of infection.

PMID- 15973125
TI  - Crohn's jejunoileitis: the pediatrician's perspective on diagnosis and
      management.
AB  - Although uncommon, diffuse jejunoilietis is one of the most difficult areas in
      Crohn's disease (CD) to treat. Although the exact frequency is unknown, most
      gastroenterologists believe that its prevalence has been underestimated and that
      it may have an increased incidence among children and young adolescents. The
      clinical importance of this clinical disease phenotype is the impact diffuse
      small bowel disease is expected to have on a child's growth and development.
      Moreover, patients with jejunoileitis are more likely to experience
      complications, including fistulization, and most commonly, intestinal
      obstruction. The associated morbidity and frequent need for surgical intervention
      renders these patients at risk for intestinal insufficiency. Although
      stricturoplasty has reduced the incidence of short bowel syndrome, most patients
      with proximal small bowel CD still require repeated surgical intervention.
      Jejunoileitis represents a distinct clinical phenotype within the heterogenous
      family of disease phenotypes considered as CD. Whether a specific genotype will
      be found to associate with jejunoileitis remains to be determined. Through the
      development of novel diagnostic techniques, including gadolinium enhanced
      magnetic resonance imaging (GMRI), enteroscopy, and capsule endoscopy, the mean
      age at diagnosis is expected to decrease. Coupled with an increase in clinical
      suspicion, early diagnosis may allow physicians to consider implementing
      aggressive immunomodulatory therapy. Future studies are needed to determine if
      the early detection and use of immune modulators in patients with proximal small
      bowel disease will improve overall quality of life and decrease the risk of
      nutritional and surgical comorbidity.

PMID- 15973126
TI  - How "NICE" were we with infliximab?

PMID- 15973127
TI  - Inflammatory bowel diseases and atherosclerosis: do we need more studies?

PMID- 15973128
TI  - Is non-adherence to blame?

PMID- 15973129
TI  - The first trial of phase contrast imaging for digital full-field mammography
      using a practical molybdenum x-ray tube.
AB  - RATIONALE AND OBJECTIVES: The image quality of a newly developed full-field
      digital phase contrast mammography (PCM) system and of a conventional screen-film
      (SF) mammography system were compared via images of a phantom and receiver
      operating characteristic (ROC) analysis of clinical images. METHODS: Magnified
      (1.75X) PCM images were scanned (sampling rate, 43.75 microm) and then reduced to
      original-sized, 25-micron pixel images printed on photothermographic film. Along
      with corresponding SF images, the phantom images were evaluated subjectively, and
      the clinical images of 38 patients were subjected to ROC analysis of mass and
      microcalcification. RESULTS: In the image quality of a phantom, the PCM exceeded
      the SF. In both mass and microcalcification, the ROC analysis Az values of the
      PCM clinical images surpassed those of the SF images. CONCLUSION: The PCM
      provides better images than the SF. Clinical trials suggest superior detection of
      both mass and microcalcification by full-field digital PCM over conventional SF
      mammography.

PMID- 15973130
TI  - Digital mammography using iodine-based contrast media: initial clinical
      experience with dynamic contrast medium enhancement.
AB  - PURPOSE: We sought to evaluate the potential of dynamic contrast enhancement
      after the intravenous administration of an iodine-based contrast medium in full
      field digital mammography. MATERIAL AND METHODS: A protocol for image acquisition
      was established for contrast-enhanced mammography and the mammography unit
      (Senographe 2000D, GE Healthcare, Buc, France) changed as required. The effect of
      the protocol parameters on imaging was investigated. Subsequently, 21 patients
      with 25 suspicious lesions of the breast (10 benign, 1 borderline, and 14
      malignant) underwent mammography with administration of an iodine-based contrast
      medium (Ultravist 370, Schering AG, Berlin, Germany), after approval of ethical
      committee as well as permission of German federal office for Radiation
      protection, and informed consent from each patient was obtained. Three sequential
      digital mammographic images of the respective breast were acquired after
      administration of the contrast medium at a dose of 1 mL/kg body weight and a flow
      of 4 mL/s. The postcontrast images were acquired 60, 120, and 180 seconds after
      administration. Subsequently, the precontrast image was logarithmically
      subtracted from the postcontrast images. Enhancement of the lesions was measured
      in absolute terms as well as relative to the enhancement of the glandular tissue.
      The subtracted images were evaluated for lesion depiction and dynamic contrast
      enhancement. Lesion-enhancement kinetics were compared with the histologic
      findings. RESULTS: All malignant lesions were identified on the contrast-enhanced
      images of digital mammography. Three of the tumors (2 malignant, 1 benign) were
      detected only by contrast-enhanced mammography and not by standard mammography.
      Dynamic enhancement curves of benign and malignant tumors in contrast-enhanced
      mammography look similar to the curves known from gadolinium-enhanced magnetic
      resonance imaging. Nevertheless differentiation between malignant and benign
      tumors based on the enhancement patterns cannot be directly taken over from
      magnetic resonance imaging, as suggested by our initial results. The results are
      somewhat better when tumor enhancement relative to surrounding glandular tissue
      is used instead of absolute enhancement. CONCLUSION: The results of this
      preliminary study suggest that contrast-enhanced digital mammography is a
      potentially useful tool for the detection and the differentiation of benign and
      malignant breast lesions.

PMID- 15973131
TI  - Evaluation of 1H-magnetic resonance spectroscopy of breast cancer pre- and
      postgadolinium administration.
AB  - OBJECTIVES: We sought to evaluate spectroscopic measurements in breast cancer and
      compare variability in choline peak parameters related to contrast administration
      versus that inherent to repeated measurements. MATERIALS AND METHODS: Single
      voxel, proton spectroscopy measurements were obtained before and after the
      administration of gadolinium on 15 patients with > or = 1-cm breast cancers. The
      protocol was repeated on a separate day in 7 patients. RESULTS: Postcontrast
      spectra demonstrated a significant increase in choline peak linewidth (day 1: 15%
      +/- 21%, P = 0.03; day 2: 19% +/- 12%, P = 0.001) and decrease in choline peak
      area (day 1: 11% +/- 9% (P < 0.001); day 2: 18% +/- 21% (P = 0.03). A variance
      components analysis indicated that day-to-day variation in linewidth accounted
      for 0.0% of the total variation in width measurements and was not significant (P
      = 0.85). Day-to-day variation in area was also not significant (0.0%, P = 0.95).
      CONCLUSIONS: Contrast administration caused significant increases in choline peak
      linewidth and decreases in choline peak area in spectroscopic measurements of
      breast cancer.

PMID- 15973132
TI  - Magnetic resonance elastography of the breast: correlation of signal intensity
      data with viscoelastic properties.
AB  - OBJECTIVES: We sought to investigate the potential value of magnetic resonance
      (MR) elastography to improve the differentiation between benign and malignant
      tumors. MATERIAL AND METHODS: Measurements of 5 patients with 6 malignant
      lesions, 11 patients with benign lesions, and 4 patients with no lesions at all
      were performed at 1.5 Tesla. After breast MR imaging, MR elastography was
      performed as a targeted measurement. Low-frequency mechanical waves (65 Hz) were
      transmitted into the breast tissue using an oscillator and were displayed by
      means of a MR sequence within the phase of the MR image. After reconstruction,
      the viscoelastic information was correlated with the signal intensity and
      morphology data. RESULTS: All examinations were technically successful realized
      in approximately 25 minutes. Malignant tumors documented higher values of
      elasticity than benign corresponding with signal intensity and morphologic data.
      CONCLUSION: A good separation exists between benign and malignant lesions in
      elasticity, corresponding with specific signal intensity and morphologic data.
      Further clinical studies with a larger number of patients are needed for extended
      validation.

PMID- 15973133
TI  - Effect of tamoxifen in an experimental model of breast tumor studied by dynamic
      contrast-enhanced magnetic resonance imaging and different contrast agents.
AB  - OBJECTIVES: The aim of this study was to compare the efficacy of gadoteridol,
      B22956/1 (a new protein binding blood pool contrast agent), and (Gd-DTPA)37
      albumin in detecting, by dynamic contrast-enhanced magnetic resonance imaging
      (MRI), the effect in vivo of tamoxifen in an experimental model of breast tumor
      implanted in rats. MATERIALS AND METHODS: Tumors were induced by subcutaneous
      injection of 10 mammary adenocarcinoma cells (13762 MAT B III). Treatment with
      tamoxifen (or vehicle) started on day 4 after implantation. On day 10 after
      implantation, animals were observed by MRI using B22956/1 (or gadoteridol) and,
      24 hours later, using (Gd-DTPA)37-albumin. RESULTS: Dynamic contrast-enhanced
      magnetic resonance imaging data showed that tamoxifen treatment decreased
      vascular permeability to B22956/1, whereas no difference was detectable in
      permeability to gadoteridol or to (Gd-DTPA)37-albumin. No effect on fractional
      plasma volume was detected with either of contrast agents. CONCLUSIONS: B22956/1
      is superior to both small Gd chelates and macromolecular contrast agents in the
      assessment of the effect of tamoxifen treatment on tumor vasculature.

PMID- 15973134
TI  - Further signs in the evaluation of magnetic resonance mammography: a
      retrospective study.
AB  - PURPOSE: To increase accuracy and reliability of magnetic resonance breast
      imaging, a new evaluation method might be helpful. The recently suggested
      evaluation method (Fischer U, et al) resulted in a relevant number of equivocal
      cases (3 or 4 points). Additional morphologic and dynamic signs as an extension
      of this score were evaluated. METHOD AND MATERIALS: One hundred thirty-two
      histologically verified lesions were evaluated by 3 radiologists double-blinded
      using 2 evaluation methods: 1) method 1 (according to Fischer, et al): 2pt:
      initial signal increase >100%, washout, centripetal enhancement, 1pt: initial
      signal increase 50-100%, plateau phenomenon, centrifugal inhomogeneous
      enhancement, irregular borders, linear, stellar or dendritic structure; and 2)
      method 2 (according to Malich, et al): 3pt: hook sign (sign of pectoral
      invasion), 2pt: unifocal edema, blooming. 1pt: hypointensity in T2, lymph nodes
      >10 mm, skin thickening, adjacent vessels, a lesion's distorted inner
      architecture, disruption of the mamillary edge; -1pt: isointensity in T2, no
      edema, enhancing septations; -3pt: hyperintensity in T2, non enhancing
      septations. Method 1 judged a lesion to be malignant if 5 or more points were
      given and benign if 2 or less points were given, respectively. Method 2 (mean
      value of 3 radiologists) was tested in those cases in which a clear possible
      decision using method 1 was not sufficiently possible. RESULTS: Method 1 alone
      resulted in a negative predictive value of 96.8% and a positive predictive value
      of 90.8% (without carcinoma in situ), a sensitivity of 83.1%, a specificity of
      58.8%, and revealed uncertain results (3 and 4 points) in 29 cases (out of 132;
      22%). Adding the new scoring system in these 29 equivocal cases and an increase
      of 2 or more points by using method 2 is supposed to be a sign of malignancy;
      findings suggest a sensitivity of 90.9% and a specificity of 60% if an increase
      of maximum 1 is observed in benign lesions. In conclusion, our results show that
      Gottingen score alone has a sensitivity of 83.1%, a specificity of 58.8%; the
      second evaluation method reveals a sensitivity of 90.9% and a specificity of 60%
      in equivocal cases of Gottingen score. Gottingen score then reaches in all cases
      and second, adding the second evaluation method in equivocal cases, a sensitivity
      of 97% and a specificity of 76.5%. CONCLUSION: The application of a second
      evaluation method in those cases remaining unclear in Gottingen score can lead to
      a decrease of uncertainty and a higher sensitivity and specificity of diagnosis
      in MR mammography. In this study, Gottingen score reaches a sensitivity of 83.1%
      and a specificity of 58.8%, increasing to a sensitivity of 97% and a specificity
      of 76.5% when being extended by a second evaluation method in unclear cases.

PMID- 15973135
TI  - Magnetic resonance imaging characteristics of fibrocystic change of the breast.
AB  - OBJECTIVE: The objective of this study was to identify magnetic resonance imaging
      (MRI) characteristics of fibrocystic change (FCC) of the breast. MATERIALS AND
      METHODS: Fourteen patients with a histopathologic diagnosis of solitary FCC of
      the breast underwent x-ray mammography and MRI of the breast. Three experienced
      breast imaging radiologists retrospectively reviewed the MRI findings and
      categorized the lesions on morphologic and kinetic criteria according to the ACR
      BI-RADS-MRI Lexicon. RESULTS: The most striking morphologic feature of
      fibrocystic change was nonmass-like regional enhancement found in 6 of 14 (43%)
      FCC lesions. Based on morphologic criteria alone, 12 of 14 (86%) lesions were
      correctly classified as benign. According to analysis of the time-intensity
      curves, 10 of 14 (71%) FCC lesions were correctly classified as benign.
      CONCLUSION: Although FCC has a wide spectrum of morphologic and kinetic features
      on MRI, it most often presents as a mass or a nonmass-like regional enhancing
      lesion with benign enhancement kinetics.

PMID- 15973136
TI  - Classification of signal-time curves obtained by dynamic magnetic resonance
      mammography: statistical comparison of quantitative methods.
AB  - OBJECTIVE: This study compares the performance of quantitative methods for the
      characterization of signal-time curves acquired by dynamic contrast-enhanced
      magnetic resonance mammography from 253 females. MATERIALS AND METHODS: Signal
      time curves obtained from 105 parenchyma, 162 malignant, and 91 benign tissue
      regions were examined (243 lesions were histopathologically validated). A neural
      network, a nearest-neighbor, and a threshold classifier were applied to either
      the entire signal-time curve or pharmacokinetic and descriptive parameters
      calculated from the curves to differentiate between 2 (malignant or benign) or 3
      tissue classes (malignant, benign, or parenchyma). The classifiers were tuned and
      evaluated according to their performance on 2 distinct subsets of the curves.
      RESULTS: The accuracy determined for the neural network and the nearest-neighbor
      classifiers was nearly identical (approximately 80% in case of 3 tissue classes,
      and approximately 76% in case of the 2 classes). In contrast, the accuracy of the
      threshold classifier applied to the discrimination of 3 classes was low (65%).
      CONCLUSION: Quantitative classifiers can support the radiologist in the diagnosis
      of breast lesions.

PMID- 15973137
TI  - Color-coded automated signal intensity curves for detection and characterization
      of breast lesions: preliminary evaluation of a new software package for
      integrated magnetic resonance-based breast imaging.
AB  - OBJECTIVES: The objective of this study was to evaluate the value of a color
      coded automated signal intensity curve software package for contrast-enhanced
      magnetic resonance mammography (CE-MRM) in patients with suspected breast cancer.
      MATERIALS AND METHODS: Thirty-six women with suspected breast cancer based on
      mammographic and sonographic examinations were preoperatively evaluated on CE
      MRM. CE-MRM was performed on a 1.5-T magnet using a 2D Flash dynamic T1-weighted
      sequence. A dosage of 0.1 mmol/kg of Gd-BOPTA was administered at a flow rate of
      2 mL/s followed by 10 mL of saline. Images were analyzed with the new software
      package and separately with a standard display method. Statistical comparison was
      performed of the confidence for lesion detection and characterization with the 2
      methods and of the diagnostic accuracy for characterization compared with
      histopathologic findings. RESULTS: At pathology, 54 malignant lesions and 14
      benign lesions were evaluated. All 68 (100%) lesions were detected with both
      methods and good correlation with histopathologic specimens was obtained.
      Confidence for both detection and characterization was significantly (P < or =
      0.025) better with the color-coded method, although no difference (P > 0.05)
      between the methods was noted in terms of the sensitivity, specificity, and
      overall accuracy for lesion characterization. Excellent agreement between the 2
      methods was noted for both the determination of lesion size (kappa = 0.77) and
      determination of SI/T curves (kappa = 0.85). CONCLUSIONS: The novel color-coded
      signal intensity curve software allows lesions to be visualized as false color
      maps that correspond to conventional signal intensity time curves. Detection and
      characterization of breast lesions with this method is quick and easily
      interpretable.

PMID- 15973138
TI  - Magnetic resonance-guided large-core breast biopsy inside a 1.5-T magnetic
      resonance scanner using an automatic system: in vitro experiments and preliminary
      clinical experience in four patients.
AB  - RATIONALE AND OBJECTIVE: The aim of this study was to investigate the feasibility
      and the precision of magnetic resonance (MR)-guided large-core breast biopsies
      (LCBB) by using the second prototype of an automatic system (ROBITOM II), which
      is used to localize lesions while operating at the isocenter of a 1.5-T whole
      body scanner. METHODS AND MATERIALS: In comparison to the first prototype,
      ROBITOM II is equipped with a dedicated double breast coil and a high-speed
      trocar setting unit. In vitro experiments (n = 25) with grapefruit phantoms,
      which contained multiple vitamin E capsules (12 x 7 mm in size) as artificial
      lesions, were performed. Four patients with MR-detectable breast lesions
      underwent biopsy. A trocar was positioned in front of the lesion and inserted
      into the breast. Specimens were harvested with a coaxial technique by using a 14
      G core needle biopsy gun. RESULTS: In all 25 in vitro experiments, capsule
      material was detected in the specimen cylinder. In 4 patients, the coaxial needle
      was detected exactly at the expected position. Between 8 and 16 tissue cylinders
      were harvested. Histologic evaluation resulted in 1 invasive ductal carcinoma and
      1 papilloma, which were confirmed after open surgery. One patient who had a
      proven breast cancer was biopsied for exclusion of multifocal disease. She showed
      fibrocystic changes, whereas open surgery revealed 3 small areas of ductal
      carcinoma in situ (DCIS). Another patient showed fibroadenoma after biopsy. This
      patient is in the follow-up period, which has lasted between 3 and 4 months up
      until now. CONCLUSIONS: In this pilot patient study, the feasibility of
      manipulator-assisted large-core breast biopsy inside a 1.5-T whole-body scanner
      was demonstrated by using ROBITOM II. The precision of the device was confirmed
      with in vitro experiments. Although these findings are preliminary and the follow
      up period is rather short, they nevertheless represent a successful proof-of
      principle of LCBB with ROBITOM II.

PMID- 15973139
TI  - Evaluation of the stereotactic 8G vacuum-assisted breast biopsy in the histologic
      evaluation of suspicious mammography findings (BI-RADS IV).
AB  - PURPOSE: The purpose of this study was to evaluate the potential of the new 8G
      stereotactic vacuum-assisted breast biopsy (ST-driver, Mammotome; Ethicon
      Endosurgery) in the histologic evaluation of BI-RADS IV microcalcifications.
      MATERIALS AND METHODS: Fifty-eight patients with 61 mammographic BI-RADS IV
      microcalcifications underwent stereotactic vacuum-assisted breast biopsy (SVAB).
      The new 8G system was mounted on the ST driver, which was formerly used only with
      the hand-held version under sonographic guidance. The evaluation criteria for
      each biopsy were minimally invasive and operative histologies, the time needed
      for biopsy, the amount of bleeding, number of rotations and specimen, the degree
      of resection, and the complications. RESULTS: Fifty-eight of 61 biopsies were
      technically successful because > or = 50% were resected (29 x 100%, 8 x 90%, 5 x
      80%, 6 x 70%, 3 x 50%, 3 x 0%). In 7 cases with representative biopsies of
      segmental suspicious microcalcifications, the degree of resection could not be
      exactly measured. All but 2 biopsies were performed without clinically relevant
      complications and after gaining enough specimens (O 12.6 specimen, 1.85
      rotations). Those 2 patients showed evidence of severe bleeding into the breast
      tissue and operative revision had to be performed (3.5%). The size of
      intramammary hematoma was measurable in 27 biopsies and showed a range from 0.5
      to 5 cm (O 2.7 cm). The average external bleeding was still low with 16 mL (5-80
      mL). In 3 of 61 lesions, it was not possible to gain representative tissue as a
      result of displacement of the lesion after introducing or shooting the needle.
      The average time needed for all biopsies was 28.2 minutes for all but 5 very
      complicated biopsies, which took 16.1 minutes. The histologic findings with
      further operative workup were: 10 ductal carcinomas in situ (DCIS), 4 atypical
      ductal hyperplasias, 1 atypical lobular hyperplasias (ALH), 3 lobular carcinomas
      in situ (LCIS), and 6 invasive ductal carcinomas. In 7 of 12 of the initial DCIS
      histologies, the operative histology was also DCIS, whereas in 4 of 12, no
      residual malignant tumor was found. In 1 of 12 patients with an initial DCIS
      histology, operative histology revealed invasive ductal cancer (8.3%). The cases
      with lobular lesions (ALH, LCIS) did not show any evidence for residual tissue in
      the operative workup. Most frequent benign histologies were mastopathy (13),
      ductal hyperplasia (9), fibroadenoma (8), and sclerosing adenosis (5). The
      control examinations (maximum 1 year) did not show any signs for a false-negative
      biopsy. CONCLUSION: The 11-G SVAB has proven to be a perfect adjunct to the
      existing breast biopsy methods. The new 8G SVAB speeds up the method when used
      for the same size of lesions and enables the user to representatively biopsy
      lesions up to 3 cm in diameter. The method is still minimally invasive; however,
      the amount of hematomas as well as clinically relevant complications is
      increased.

PMID- 15973140
TI  - Ultrasound-guided, percutaneous cryotherapy of small (< or = 15 mm) breast
      cancers.
AB  - RATIONALE AND OBJECTIVE: The purpose of this study was to investigate the
      feasibility, efficacy, and safety of ultrasound-guided percutaneous cryotherapy
      of stage T1 breast cancers. MATERIALS AND METHODS: Thirty patients with biopsy
      confirmed breast cancers with tumor diameters of 15 mm or smaller (range, 5-15
      mm; median, 12 mm) underwent cryotherapy. After local anesthesia, a 3-mm cryo
      probe was placed into the tumor under ultrasound guidance. All tumors were
      subjected to 2 freeze cycles with an interposing thawing cycle. The size of the
      ice-balls, their distance to the skin, and the temperature at the tip of the
      probe were closely monitored during the procedure. The patients underwent surgery
      within 6 weeks and the specimens were evaluated histologically. RESULTS: The
      median minimum temperature reached -146 degrees C (range, -117 degrees C to -167
      degrees C). In 5 of 29 patients, remnant ductal carcinoma in situ was detectable
      histologically after cryotherapy beyond the margin of the cryosite in the
      specimens after open surgery. In 24 patients, no viable tumor cells were found.
      No severe side effects occurred. In one patient, the cryo procedure was not
      performed completely because of technical problems. DISCUSSION: Percutaneous
      cryotherapy is a feasible and safe procedure in minimally invasive therapy for
      small breast cancers. Residual ductal carcinoma in situ may be attributable to
      the beginning of a learning curve or by false-negative detection in pre
      interventional imaging. Magnetic resonance mammography might aid in treatment
      planning and for therapy monitoring to better define target tissue and to
      correlate the tumor margin with the ice-ball.

PMID- 15973141
TI  - The negative predictive value of electrical impedance scanning in BI-RADS
      category IV breast lesions.
AB  - OBJECTIVES: We sought to prospectively assess the value of electrical impedance
      scanning (EIS) in discriminating benign from malignant lesions classified as BI
      RADS category IV in mammography in comparison with ultrasound (US), with a
      special focus on negative prediction. MATERIALS AND METHODS: EIS was performed on
      128 BI-RADS category IV lesions in 121 women (mean, 51.8 years). The newly
      developed EIS software 2.67 calculates a BI-RADS-like level of suspicion (LOS) on
      a 5-grade scale. LOS 1, 2, and 3 were considered negative; LOS 4 and 5 were
      considered positive. Histopathologic results were obtained in all lesions.
      RESULTS: Histology proved 37 lesions malignant, 91 benign. Sensitivity,
      specificity, accuracy, positive predictive value (PPV), and negative predictive
      value (NPV) of EIS compared with US were 94.6%, 74.7%, 80.5%, 60.3%, 97.1% versus
      90.5%, 33.8%, 47.2%, 29.7%, 92.0%, respectively. In 43 lesions sized < or = 10
      mm, EIS demonstrated better sensitivity, specificity, accuracy, PPV, and NPV of
      100%, 83.3%, 90.7%, 82.6%, and 100%, respectively. Although NPV was also high, US
      showed no sufficient results in 39 (30.5%) lesions because of
      microcalcifications. Receiver operating curve analysis revealed best results for
      a combined use of US and EIS. CONCLUSIONS: With a NPV of 97.1% of EIS in BI-RADS
      category IV breast lesions, a negative result in these lesions could be firm
      indication to manage them as BI-RADS-category III and refer patients for a 6
      month short-interval follow-up rather than performing a biopsy. The best
      adjunctive diagnostic performance can be achieved by a combination of US and EIS.
      Costs and patient morbidity could be minimized.

PMID- 15973142
TI  - Diffractive ultrasound in the evaluation of solid breast masses: preliminary
      results.
AB  - PURPOSE: We sought to evaluate diffractive ultrasound (US) in the
      characterization of solid breast masses. MATERIALS AND METHODS: Forty-eight
      patients with solid breast masses (24 malignant and 24 benign) observed at
      conventional US underwent targeted diffractive US before needle biopsy or
      surgery. The process of locating the lesion was performed with knowledge of the
      mammography and conventional US. On diffractive US, imaging features, including
      shape, brightness, echotexture, margin, and boundary echo were analyzed and odds
      ratio (OR) were calculated to show how the risk of malignancy was altered by the
      presence of a given finding. RESULTS: Of the 48 solid breast masses seen on
      conventional US, 46 (96%) were seen at diffractive US. Diffractive US features
      suggestive of malignancy were irregular shape (OR 11.5), sono-opacity (OR 204),
      spiculated margin (OR 17.0), and absent boundary echo (OR 11.5) or thick rim (OR
      5.5), whereas those of benignancy were round shape (OR 0.03), sonotransmission
      (OR 0.07) or isodensity (OR 0.01), well-defined margin (OR 0.03), and thin
      capsule (OR 0.03; P < 0.05). CONCLUSION: The finding of a sono-opaque mass on
      diffractive US was highly sensitive for malignancy. Further improvement of
      diffractive US equipment is needed to increase image quality and to permit
      inclusion of the axillary tail and deep portions of the breast.

PMID- 15973143
TI  - Visual task complexity modulates the brain's response to unattended auditory
      novelty.
AB  - New, unusual, and changing events are important environmental cues, and the
      ability to detect these types of stimuli in the environment constitutes a
      biologically significant survival skill. We used event-related potentials to
      examine whether sensory and cognitive neural responses to unattended novel events
      are modulated by the complexity of a primary visuomotor task. Event-related
      potentials were elicited by unattended task-irrelevant pitch-deviant tones and
      novel environmental sounds while study participants performed a continuous
      visuomotor tracking task at two levels of difficulty, achieved by manipulating
      the control dynamics of a joystick. The results revealed that increased task
      complexity modulated evoked sensory and cognitive event-related potential
      components, indicating that detection of change and novelty in the unattended
      auditory channel is resource-limited.

PMID- 15973144
TI  - Visual areas involved in the perception of human movement from dynamic form
      analysis.
AB  - The perception of biological motion combines the analysis of form and motion.
      However, patient observations by Vaina et al. and psychophysical experiments by
      Beintema and Lappe showed that humans could perceive human movements (a walker)
      without local image motion information. Here, we examine the specificity of brain
      regions responsive to a biological motion stimulus without local image motion,
      using functional magnetic resonance imaging. We used the stimulus from Beintema
      and Lappe and compared the brain activity with a point-light display that does
      contain local motion information and was often used in previous studies. Recent
      imaging studies have identified areas sensitive to biological motion in both the
      motion-processing and the form-processing pathways of the visual system. We find
      a similar neuronal network engaged in biological motion perception, but more
      strongly manifested in form-processing than in motion-processing areas, namely,
      fusiform-/occipital face area and extrastriate body area.

PMID- 15973145
TI  - Brain activation related to retrosaccades in saccade experiments.
AB  - In saccade experiments, each trial (e.g. prosaccade/antisaccade) is by definition
      followed by a saccade, which returns the gaze back to the center (retrosaccade).
      This event can complicate brain-imaging results when using a simple block-design.
      We used an event-related functional magnetic resonance imaging design involving
      prosaccades and antisaccades (testsaccades) to examine brain activation
      associated with retrosaccades. Testsaccades activated visual and oculomotor
      related brain areas. During retrosaccades, these areas were less active than
      during testsaccades. In the supplementary eye fields, the insula, and striatum,
      the retrosaccades gave rise to negative blood oxygenation level-dependent
      responses. In the striatum, these negative responses were equal in size to the
      positive responses of the testsaccades. This could mask brain activity of
      testsaccades when not taken into account.

PMID- 15973146
TI  - Disrupted white matter tract integrity of anterior cingulate in trauma survivors.
AB  - The objective of this study was to examine the integrity of whole-brain white
      matter in posttraumatic stress disorder patients. Twenty posttraumatic stress
      disorder patients who survived the Taegu subway fire incident and 20 healthy
      volunteers participated in this study. Statistical parametric mapping was used to
      evaluate the global differences in fractional anisotropy values between the two
      groups. The results show that posttraumatic stress disorder patients had
      significantly lower fractional anisotropy values in the left anterior cingulate
      regions. Posttraumatic stress disorder symptom severity negatively correlated to
      the level of decrease in anterior cingulate fractional anisotropy values. The
      outcome of the current study suggests that the disruption of the left anterior
      cingulate white matter tract integrity may play an important role in the
      pathophysiology of posttraumatic stress disorder.

PMID- 15973147
TI  - Folate deficiency inhibits proliferation of adult hippocampal progenitors.
AB  - Neurogenesis in the adult hippocampus may play important roles in learning and
      memory, and in recovery from injury. As recent findings suggest, the perturbance
      of homocysteine/folate or one-carbon metabolism can adversely affect both the
      developing and the adult brain, and increase the risk of neural tube defects and
      Alzheimer's disease. We report that dietary folic acid deficiency dramatically
      increased blood homocysteine levels and significantly reduced the number of
      proliferating cells in the dentate gyrus of the hippocampus in adult mice. In
      vitro, the perturbance of one-carbon metabolism repressed proliferation of
      cultured embryonic multipotent neuroepithelial progenitor cells and affected cell
      cycle distribution. Our results suggest that dietary folate deficiency inhibits
      proliferation of neuronal progenitor cells in the adult brain and thereby affects
      neurogenesis.

PMID- 15973148
TI  - Rare stimuli or rare changes: what really matters for the brain?
AB  - Previous research has demonstrated that the electric brain response to changes
      consists of a negative deflection with a latency of 200 ms post-stimulus. Two
      different hypotheses, namely the mismatch and the rareness accounts, have been
      invoked to explain this electrocortical response. In the present study, this
      negative component emerged only for visual changes caused by the presentation of
      rare stimuli, documenting a precise brain response to rareness, and not to change
      per se. Crucially, no specific electrophysiological marker was evident when the
      change was rare, but consisted of stimuli frequently seen. Hence, we suggest that
      changes are preferentially processed by the brain only when they involve the
      occurrence of new and rare stimuli.

PMID- 15973149
TI  - The calpain inhibitor VI prevents apoptosis of adult motor neurons.
AB  - Motor neuron cell death was studied in organotypic cultures of adult spinal cord
      slices from the mouse. Six hours after excision, many motor neuron nuclei
      displayed apoptotic features including nuclear and chromatin condensation. At
      this time point, many motor neurons also exhibited immunoreactivity to calpain
      II. Both the calpain inhibitor VI and ethyleneglycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid (EGTA) prevented the appearance of apoptotic nuclei
      whereas the pan caspase inhibitor Z-VAD.fmk had no effect. The results suggest
      that calpain is required for apoptosis of motor neurons and that this type of
      apoptosis is independent of caspase activation.

PMID- 15973150
TI  - GABAergic control of hypothalamic melanin-concentrating hormone-containing
      neurons across the sleep-waking cycle.
AB  - The perifornical-lateral hypothalamic area is implicated in regulating waking and
      paradoxical sleep. The blockade of GABAA receptors by iontophoretic applications
      of bicuculline (or gabazine) into the perifornical-lateral hypothalamic area
      induced a continuous quiet waking state associated to a robust muscle tone in
      head-restrained rats. During the effects, sleep was totally suppressed. In rats
      killed at the end of a 90 min ejection of bicuculline, Fos expression was induced
      in approximately 28% of the neurons immunoreactive for hypocretin and in
      approximately 3% of the neurons immunostained for melanin-concentrating hormone
      within the ejection site. These results suggest that neurons containing melanin
      concentrating hormone are not active during waking and that the lack of a potent
      GABAergic influence during waking is consistent with their role in sleep
      regulation.

PMID- 15973151
TI  - Age-related effects on superior temporal gyrus activity during an auditory
      oddball task.
AB  - We used magnetoencephalography in combination with magnetic resonance imaging to
      investigate the effects of aging on the temporal dynamics of activity localized
      to several brain regions during an auditory oddball task. The most interesting
      effects were noted in the superior temporal gyrus as follows: (1) responses were
      generally stronger to rare than to frequent tones throughout the entire 600-ms
      time interval, and (2) increases in the amplitude of the 40-ms peak and the
      latency of the maximum late response were evident in the elderly. Although
      superior temporal gyrus activity has traditionally been associated with early
      sensory processing, these results suggest that superior temporal gyrus activity
      is also important for later decision-related processing.

PMID- 15973152
TI  - B7-homolog 1 expression by human glioma: a new mechanism of immune evasion.
AB  - Immunosuppressive soluble factors such as transforming growth factor beta and
      cell surface molecules such as FasL may contribute to the immune evasion of
      malignant glioma. B7 homolog 1 is a member of the B7 family of costimulatory
      molecules implicated in the negative regulation of T cell immune responses. Here,
      we show that human glioma cell lines express B7 homolog 1 protein that reduces
      interferon-gamma production by activated T cells. The expression of B7 homolog 1
      in vivo was demonstrated in a large series of human glioma samples, with a
      significant correlation between the level of B7 homolog 1 expression and the
      tumor grade. Overall, our data suggest that B7 homolog 1 may be involved in the
      immune evasion of glioma and encourage the blockade of this pathway in future
      immunotherapies.

PMID- 15973153
TI  - Neuroprotective effect of riluzole in acute noise-induced hearing loss.
AB  - Riluzole has been reported to protect against the deleterious effect of cerebral
      ischemia by blocking glutamatergic neurotransmission. Here, we investigated
      whether acoustic trauma-induced cochlear excitotoxicity could be attenuated by
      riluzole. Cumulative intracochlear perfusion of riluzole completely abolished
      single-nerve fiber activity in the guinea pig cochlea and the compound action
      potential of the auditory nerve. Guinea pigs treated with riluzole (100 microM)
      showed significantly less hearing threshold shift than untreated guinea pigs, and
      presented no sign of dendritic damage in the cochlea observable by electron
      microscopy. When coapplied with glutamate, riluzole did not prevent glutamate
      induced swelling of auditory nerve dendrites, suggesting that the protective
      effect of riluzole was mediated principally by inhibition of glutamate release
      from sensory inner hair cells.

PMID- 15973154
TI  - Age effects on pheromone induced Fos expression in olfactory bulbs of a primate.
AB  - In the gray mouse lemur, a prosimian primate, aging is associated with a
      reduction of olfactory behaviors and sexual stimulation. To assess the effect of
      aging on the central response to pheromone stimulation in this primate, we
      measured the c-fos expression in the main and accessory olfactory bulbs of adult
      and aged male mouse lemurs, following exposure to the volatile phase of urine
      from proestrous females. In adults, pheromone exposure increased the number of
      Fos-positive neurons in the main olfactory bulb without changes in the accessory
      olfactory bulb. Fos expression was not increased by the odorant stimulation in
      aged mouse lemurs. Our results may explain the age-related decrease in behaviors
      associated with olfactory stimulation in this primate.

PMID- 15973155
TI  - Assessing vestibular contributions during changes in gait trajectory.
AB  - Displacing prisms and galvanic stimulation were used to examine visual-vestibular
      interactions during target-directed gait. Participants walked towards a wall 6 m
      away. After taking four steps, a target on the wall, located directly in front or
      to the right of the participant, was illuminated. Participants continued walking
      towards the target. Galvanic vestibular stimulation was triggered at either gait
      initiation, a step before the potential turn, or at target illumination. Although
      the visual and vestibular perturbations significantly altered gait trajectory,
      the greatest interaction occurred when galvanic stimulation was triggered one
      step before the target appeared. This implies an increase in the weighting of
      vestibular inputs just before turning to prepare for the potential change in
      direction.

PMID- 15973156
TI  - Seeing the hand being touched modulates the primary somatosensory cortex.
AB  - Recent behavioral studies have shown that viewing the stimulated body part can
      enhance tactile acuity. We examined effects of viewing the stimulated body part
      by using neuromagnetic source imaging. Study participants were covertly
      stimulated on their first digit (D1) while watching a video that showed a hand
      where D1 was stimulated. The video hand appeared in the region where the real
      hand would be expected. In addition, participants were stimulated on D1 without
      watching the video. The results demonstrated a shift of D1 to a more inferior
      position and an increase of the dipole strength of D1 during the observation of
      tactile stimulation. We discuss these cross-modal interactions with recent
      studies on visuotactile enhancement.

PMID- 15973157
TI  - Touch-induced visual illusion.
AB  - Although vision is considered the dominant modality, recent studies demonstrate
      the influence of other modalities on visual perception. For example, in the sound
      induced flash illusion, two auditory stimuli cause one visual flash to be
      perceived as two. We report an extension of the sound-induced flash illusion to
      the tactile-visual domain, yielding the touch-induced flash illusion. Observers
      reported seeing two flashes on the majority of trials when a single flash was
      presented concurrently with two task-irrelevant brief tactile stimuli.
      Somatosensory stimulation changed the sensitivity (d') of detecting visual
      stimuli, which suggests that the observed effect is at least partly due to
      perceptual interactions. Together with other recent findings, these results
      challenge the notion that the processing of visual information is independent of
      activity in other modalities.

PMID- 15973158
TI  - Gene expression changes in brains of mice exposed to a maternal virus infection.
AB  - In this study, we tested the hypothesis that exposure to a maternal infection
      during fetal life can lead to the appearance of alterations in the brain later in
      life. C57BL/6 mice were infected intranasally with influenza A/WSN/33 virus on
      day 14 of gestation. The levels of transcripts encoding neuroleukin and
      fibroblast growth factor 5 were significantly elevated in the brains of the virus
      exposed offspring at 90 and 280 days of age, but not at earlier time-points. For
      neuroleukin, this difference could also be observed at the protein level. Thus, a
      maternal influenza A virus infection can give rise to alterations in gene
      expression in the brain that become apparent only after a prepubertal latency
      period.

PMID- 15973159
TI  - Neuroprotection of Parkin against apoptosis is independent of inclusion body
      formation.
AB  - Loss-of-function mutations in the parkin gene are known to result in autosomal
      recessive juvenile parkinsonism, which causes selective degeneration of
      nigrostriatal dopaminergic neurons in the absence of Lewy bodies. Here, we show
      that overexpression of parkin protects PC12 cells from neurotoxin of the
      proteasome inhibitor lactacystin and increases the accumulation of ubiquitin
      protein conjugates and the formation of ubiquitin-positive inclusions induced by
      lactacystin. However, the protective effect of parkin against lactacystin-induced
      apoptosis is not associated with its ability to promote the formation of
      ubiquitinated inclusions. It is likely that Lewy body formation may be only a
      compensatory mechanism of dopaminergic neurons attempting to counteract toxicity,
      and not the ultimate cause of neuronal death.

PMID- 15973160
TI  - Increased severity of experimental colitis in alpha 5 nicotinic acetylcholine
      receptor subunit-deficient mice.
AB  - Substantial evidence suggests a negative association between cigarette smoking
      and the incidence and severity of ulcerative colitis, a common human inflammatory
      bowel disease. Nicotine has been implicated in this association. The detection of
      nicotinic acetylcholine receptors in colonic epithelium, the primary tissue
      affected in ulcerative colitis, suggests a role for these receptors in the
      beneficial effect of nicotine on colonic inflammation. Using an animal model, we
      demonstrate for the first time that alpha5 nicotinic acetylcholine receptor
      knockout mice have significantly more severe experimental colitis than wild-type
      controls and that nicotine significantly ameliorates its course when compared
      with wild-type controls. These findings suggest that alpha5-containing nicotinic
      acetylcholine receptors participate in the modulation of colitis in mice, but
      other nicotinic acetylcholine receptor subunits also mediate the antiinflammatory
      effects of nicotine.

PMID- 15973161
TI  - Chronic food restriction enhances memory in mice--analysis with matched drive
      levels.
AB  - We compared the effects of chronic and acute food deprivation on learning and
      memory using a dry-type water maze, active avoidance and passive avoidance in
      C57BL/6L mice. The drive level of the animals--under acute and chronic food
      deprivation--was matched by a progressive ratio schedule. Both deprivations led
      to a high degree of activity in the animals; however, the animals on an acute
      dietary restriction did not exhibit a significantly better performance than those
      on ad libitum feeding, while those on a chronic food deprivation exhibited memory
      enhancement. These effects were subtle and were found at a later stage of
      learning. These findings suggest that chronic food restriction induces memory
      consolidation or resistance to memory reduction in addition to increased
      activity.

PMID- 15973162
TI  - Association of the functional catechol-O-methyltransferase VAL158MET polymorphism
      with the personality trait of extraversion.
AB  - Across different personality theories, there is agreement that dopamine is the
      neurochemical basis of extraversion. However, evidence from molecular genetics
      for the validity of this hypothesis is far from convincing. The functional
      polymorphism of the catechol-O-methyltransferase gene (COMT VAL158MET) has not
      been related to extraversion before, although it is a promising candidate gene
      locus for extraversion because of its great influence on the catabolism of
      dopamine. In a sample of n=363 healthy study participants, the catechol-O
      methyltransferase VAL158MET polymorphism was related to extraversion and novelty
      seeking.Results showed a significant association between catechol-O
      methyltransferase, extraversion and the subscale exploratory excitement (NS1) of
      novelty seeking but not with the total novelty-seeking scale supporting the
      psychometric analyses of the personality scales. The findings support the
      hypothesis that the dopamine system is involved in positive emotionality and
      incentive motivation, which has implications for the understanding of the
      neurochemical correlates of normal and psychopathological behaviors.

PMID- 15973163
TI  - Analysis of vascular access in intestinal transplant recipients using the Miami
      classification from the VIIIth International Small Bowel Transplant Symposium.
AB  - BACKGROUND: Loss of vascular access in patients with intestinal failure is
      considered an indication for intestinal transplantation. Such patients often have
      one or more occluded vein sites. Venous access could be classified according to
      the number of occluded vessels, to facilitate pre- and postoperative management.
      METHODS: At the VIIIth International Small Bowel Transplant Symposium in
      September 2003, a new classification of vascular access in patients who were
      candidates for bowel transplant was proposed. The classification was then applied
      to stratify all patients that underwent intestinal transplantation at the
      University of Miami between 1998 and 2003. Data were collected on Doppler
      ultrasonography, angiography, and vein angioplasty in such patients. RESULTS: A
      total of 106 cases in 91 patients were included in the study. Based on Doppler
      ultrasound results, 51.9% of patients fell into class I (no thrombosed vessels),
      21.7% were in class II (one occluded vessel, or positive risk factors for
      thrombosis), 24.5% were in class III (multiple thrombosed vessels), and 1.9% were
      in class IV (all vessels thrombosed). Fifteen percent of the patients required
      preoperative angiography to better evaluate venous access. Most of the patients
      that required angiography were in class III or IV, and 53.3% of patients
      requiring angiography needed additional venous angioplasty to achieve access.
      CONCLUSIONS: All patients that are referred for intestinal transplantation should
      undergo preliminary mapping of their venous access by Doppler ultrasound and then
      be assigned to a vascular access class. Those patients with multiple thrombosed
      vessels (class III and above) should be strongly considered for additional
      angiographic evaluation.

PMID- 15973164
TI  - Management of complex vascular access in intestinal transplantation: should we
      wait for it?

PMID- 15973165
TI  - Heat shock protein 27 in chronic allograft nephropathy: a local stress response.
AB  - BACKGROUND: Heat shock protein (HSP) 27 plays a cytoprotective role through its
      antioxidant, antiapoptotic, and actin-stabilizing properties during cell stress.
      The authors hypothesized that HSP27 is involved in chronic allograft nephropathy
      (CAN), a chronic state of inflammation and stress. METHODS: The authors used the
      Fisher 344-to-Lewis model of CAN. Transplants were performed in 3-month-old
      recipient rats. HSP27 mRNA and protein levels were determined using
      semiquantitative polymerase chain reaction, microarray (stress-toxicity, GEArray)
      analyses, gene sequencing, immunoblotting, and immunohistochemical analyses at 10
      days and 6 months posttransplant. P38 mitogen-activated protein kinase (MAPK),
      manganese (Mn) superoxide dismutase (SOD), copper-zinc (CuZn) SOD, FasL, Bax,
      hypoxia-inducible factor (HIF)-1alpha, and CD3 lymphocytes were studied in
      parallel as selective biomarkers of oxidative stress (OS), apoptosis, hypoxia,
      and graft-infiltrating immune cells. RESULTS: Six months after transplantation,
      kidney allografts displayed histologic and functional features of CAN, including
      tubular atrophy, interstitial fibrosis, glomerulosclerosis, and increased
      proteinuria and serum creatinine levels. HSP27 mRNA and protein levels in CAN
      were reduced by 50% and 85%, respectively (P=0.04). Immunohistochemical analyses
      revealed a "shift" in HSP27 from the medulla to the cortex in allografts with
      CAN. Bax, phosphorylated p38-MAPK, HIF-1alpha, and MnSOD followed a parallel
      relocation pattern. CD3 lymphocyte density and tubular FasL expression were also
      greater in the cortex of allografts with CAN. Time-course analyses revealed that
      most of these changes were present as early as 10 days posttransplant.
      CONCLUSIONS: The shift of HSP27 from the medulla to the cortex, combined with
      greater CD3, p38-MAPK, Bax, FasL, HIF-1alpha, and MnSOD immunoreactivity in this
      area of the kidney, likely represents an allograft-level response to CAN-related
      OS-hypoxia.

PMID- 15973166
TI  - The macrophage is the predominant inflammatory cell in renal allograft intimal
      arteritis.
AB  - BACKGROUND: Intimal arteritis defines acute vascular rejection in the Banff 97
      schema. The arteritis is generally considered to be lymphocytic, although the
      cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages.
      This study aimed to determine the extent of macrophage involvement in renal
      allograft intimal arteritis. METHODS: We obtained archival biopsy material from
      57 biopsies of 34 renal allografts transplanted between March 1999 and February
      2002. All biopsies were diagnostic. We examined clinical and histological
      parameters. Biopsies were graded using the Banff 97 criteria. We identified
      macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO,
      respectively. RESULTS: In all, 24 biopsies showed borderline rejection, and 12
      biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute
      rejection. Both lymphocytes and macrophages were present in the
      tubulointerstitium in all grades of acute rejection. We identified intimal
      arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably
      included CD68-positive cells; however, we saw intimal CD45RO-positive cells in
      only seven vessels. There were significantly more CD68-positive cells than CD45RO
      positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO
      cells were never the predominant component of the intimal inflammatory
      infiltrate. CONCLUSIONS: In the intimal arteritis of biopsies graded as Banff II
      or III acute rejection, the infiltrating cells were predominantly macrophages. T
      cells were in the minority. This finding challenges the assumption that the
      mononuclear cells in intimal arteritis are predominantly lymphocytic.

PMID- 15973167
TI  - Role of the thymus and kidney graft in the maintenance of tolerance to heart
      grafts in miniature swine.
AB  - BACKGROUND: The authors have examined the mechanism whereby co-transplantation of
      a kidney and heart from the same donor induces and maintains tolerance to both
      organs in miniature swine. METHODS: Transplants were performed across a major
      histocompatibility complex class I mismatch, and recipients received cyclosporine
      for 12 days. Group 1 animals received heart transplants alone (n=5), and all
      other groups received both heart and kidney allografts. Group 2 animals received
      no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8
      days after heart and kidney co-transplantation (n=2). Group 4 animals underwent
      transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were
      placed on group 4 animals, on one group 3 animal, and on two animals from group
      2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4).
      RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and
      rejection. Group 2 animals never developed CAV and demonstrated in vitro donor
      specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4
      animals developed CAV without concomitant donor-specific cell-mediated
      lympholysis reactivity, interstitial rejection, or cessation of graft function.
      Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart
      and skin grafts, in contrast to grafts on group 2 animals that had no in vivo
      effect. Group 5 animals developed CAV but no significant increase in interstitial
      infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for
      maintenance of tolerance to heart allografts.

PMID- 15973168
TI  - Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular
      xenograft rejection by mice.
AB  - BACKGROUND: Identification of the antigens that stimulate transplant rejection
      can help develop graft-specific antirejection strategies. The xenoantigens
      recognized during rejection of porcine cellular xenografts have not been clearly
      defined, but it has been assumed that major histocompatibility complex (MHC)
      xenoantigens are involved. METHODS: The role of porcine endogenous retrovirus
      (PERV) as a source of xenoantigens was examined. The authors used morphometry to
      compare the kinetics of swine leukocyte antigen (SLA) pig thyroid xenograft
      rejection in control mice and mice immunized with PERV PK15 cells (porcine kidney
      epithelial cells), PERV SLA pig peripheral blood lymphocytes (PBL), PERV virions
      purified from PK15 cells, and PERV or PERV A pseudotypes produced from infected
      human 293 cells. The tempo of rejection for cellular xenografts of PERV A
      pseudotype-producing human 293 cells, uninfected human 293 cells, and PK15 cells
      in PERV-preimmunized and control mice was also compared. RESULTS: Mice immunized
      with PK15 cells rejected pig thyroid xenografts significantly faster at day 5
      than control mice and mice immunized with pig PBL. This correlated with the
      amount of PERV RNA and virions produced, but not with the amount of SLA class I
      MHC expressed by PK15 cells. Immunization of mice with PERV virions purified from
      porcine PK15 cells and with PERV virions or PERV A pseudotypes produced by human
      293 cells also induced accelerated xenograft rejection by 5 days. Accelerated
      rejection induced by virus pretreatment was CD4 T-cell dependent and restricted
      to PERV-expressing cellular xenografts of porcine or nonporcine origin.
      CONCLUSIONS: PERV acts as a significant source of xenoantigens that target
      porcine cellular xenografts for rejection.

PMID- 15973169
TI  - Aging and transplant arteriosclerosis in absence of alloreactivity and
      immunosuppressive drugs in a rat aortic model: recipient age's contribution.
AB  - BACKGROUND: Almost half of all transplanted vascularized organ grafts will be
      lost to transplant arteriosclerosis sometime posttransplantation. Organ shortage
      for primary transplants and retransplants has led to donor-pool expansion to
      include elderly donors, knowing that aging per se promotes arteriosclerosis. The
      current understanding that donor age negatively affects organ and/or patient
      survival outcome is undermined by variables such as the use of immunosuppressive
      drugs, their toxicity to the graft, degree of donor-recipient histocompatibility,
      and the resulting chronic rejection. The purpose of this study was to determine
      whether the donor's age or recipient's age matters the most in transplant
      arteriosclerosis in the absence of such variables. METHODS: A syngeneic
      combination was used where young (2-month-old) and old (22-month-old) donor
      aortas were injured to initiate neointimal thickening, then transplanted into age
      mismatched recipients for 14, 60, and 90 days and then assessed for neointimal
      thickening. Base level injury response due ischemia and surgery was evaluated in
      age-matched and noninjured aortic grafts, respectively. RESULTS: Young aortas
      invariably developed thicker neointima when transplanted into old recipients than
      when transplanted into young ones. Correspondingly, old aortas transplanted in
      young recipients consistently developed less neointimal thickening than when
      transplanted into old recipients. CONCLUSIONS: Our findings strongly suggest that
      the severity of age-related neointima formation is primarily determined by the
      recipient's age rather than the donor's age. Therefore, in addition to focusing
      on donor-specific tolerance induction, strategies aiming at increasing the
      lifespan of vascularized organ grafts also have to take into consideration the
      recipient's aging milieu.

PMID- 15973170
TI  - Remote ischemic preconditioning of the recipient reduces myocardial ischemia
      reperfusion injury of the denervated donor heart via a Katp channel-dependent
      mechanism.
AB  - BACKGROUND: We assess whether remote ischemic preconditioning (rIPC) of the
      recipient can modify ischemia-reperfusion (IR) injury in the donor heart
      following orthotopic heart transplantation from brain dead donors and to examine
      potential mechanisms of protection. METHODS: Sixteen pigs weighing from 26 to
      34.2 (mean 29.2) kg, randomized to control group (n=5), ischemic preconditioning
      (rIPC) group (n=6), and to receive rIPC with prior glibenclamide administration
      (Glib + rIPC) group (n=5) underwent orthotopic heart transplantation with the
      support of hypothermic (32 degrees C) cardiopulmonary bypass (CPB). The hearts
      were harvested from donor animal rendered brain dead by balloon compression via a
      craniotomy. Preconditioning of the recipients was induced by four 5-min cycles of
      lower limb ischemia. Myocardial infarction (MI) was induced following heart
      transplantation by 30 min of left anterior descending (LAD) artery occlusion
      following by 2 hr of regional reperfusion. The extent of myocardial infarction
      was assessed by triphenyltetrazolium (TTC) staining. RESULTS: Preconditioning of
      the recipient reduced the mass of MI (6.75+/-6.3 g in rIPC vs. 18.1+/-5.8 g in
      control, P=0.01), MI to area at risk (ARR) mass ratio by 57% (15.6%+/-15.2% vs.
      36.3%+/-13.4%, P=0.04). The protective effect of preconditioning was abolished by
      pretreatment with glibenclamide. CONCLUSIONS: Remote ischemic preconditioning of
      the recipient, decreases ischemia-reperfusion injury in the brain dead donor
      heart following orthotopic heart transplantation via a Katp channel-dependent
      mechanism. This study suggests that a circulating effector persists after the
      rIPC stimulus is applied, and excludes an ongoing afferent neurogenic mechanism
      of cardioprotection.

PMID- 15973171
TI  - Improved success of myoblast transplantation in mdx mice by blocking the
      myostatin signal.
AB  - BACKGROUND: : Duchenne muscular dystrophy (DMD) is caused by a dystrophin gene
      mutation. Transplantation of normal myoblasts results in long-term restoration of
      dystrophin. However, the success of this approach is compromised by the limited
      time of regeneration following muscle damage. Myostatin is known to be
      responsible for limiting skeletal muscle regeneration. Our purpose is to verify
      whether blocking the myostatin signal in mdx host mice or in normal myoblasts
      transplanted in mdx host mice would increase the extent of muscle repair and thus
      allow the formation of more dystrophin-positive fibers. METHODS: : Transgenic mdx
      mice carrying a dominant negative form of myostatin receptor (dnActRIIB) were
      used to test the fiber resistance to damage and to act as a host for normal
      myoblast transplantation. Myoblasts obtained from nondystrophic transgenic mice
      carrying the dominant negative myostatin receptor were also transplanted in
      nontransgenic mdx mice. RESULTS: : Transgenic mdx mice carrying the dnActRIIB
      gene have bigger muscles than mdx mice with the normal gene of ActRIIB. Their
      fiber resistance to exercise-induced damage was also greatly improved. Moreover,
      the success of normal myoblast transplantation was significantly enhanced in
      mdx/dnActRIIB mice. Finally, nondystrophic dnActRIIB myoblasts formed more
      abundant and bigger dystrophin positive fibers when transplanted in mdx mice.
      CONCLUSIONS: : Blocking the myostatin signal in mdx mice allowed the size of
      muscle fibers to increase, the fiber resistance to damage induced by exercise to
      increase, and the success of normal myoblast transplantation to improve. The
      transplantation in mdx mice of dnActRIIB myoblasts formed more abundant and
      larger dystrophin positive fibers.

PMID- 15973172
TI  - Protection of mouse small bowel allografts by FTY720 and costimulation blockade.
AB  - BACKGROUND: The clinical application of small bowel transplantation (SBTx) is
      hampered by its pronounced immunogenicity. We aimed to test the hypothesis that
      prolonged sequestration of lymphocytes in secondary lymphoid organs may enhance
      the alloprotective effect of costimulation blockade. METHODS: For this purpose,
      recipients of intestinal allografts were treated with MR1, FTY720, combined
      FTY720 plus MR1, or were left untreated. Grafts were examined 6 and 14 days after
      transplantation by applying a histologic rejection score, multiparameter
      immunofluorescent staining, and flow cytometry. RESULTS: FTY720 or MR1
      monotherapy did not prevent the rejection of mouse intestinal allografts, whereas
      combined therapy with FTY720 plus MR1 profoundly inhibited rejection at day 6 and
      day 14 after transplantation. In FTY720-treated mice infiltration of host
      lymphocytes in graft mesenteric lymph nodes, Peyer's patches, intraepithelial
      lymphocytes, and lamina propria lymphocytes (LPLs) was reduced on day 6. Anti
      CD40L antibody improved the rejection score at day 14 but had no effect at day 6.
      Importantly, host CD8 T-cell infiltration in graft LPLs was significantly reduced
      compared with all other groups. CONCLUSION: FTY720 plus MR1 effectively inhibited
      intestinal allograft rejection in mice, possibly by enhancing the alloprotective
      effects of costimulation blockade by prolonged sequestration of lymphocytes in
      secondary lymphoid organs.

PMID- 15973173
TI  - Dynamic tissue perfusion measurement: a novel tool in follow-up of renal
      transplants.
AB  - BACKGROUND: The authors applied the novel method of noninvasive dynamic color
      Doppler sonographic parenchymal perfusion measurement to renal transplants.
      METHODS: Color Doppler sonographic videos of renal transplants from 38 renal
      transplant recipients were recorded under defined conditions. Specific tissue
      perfusion was calculated as mean flow velocity encoded by color Doppler signals
      of a region of interest during one full heart cycle. RESULTS: The authors could
      demonstrate significant differences of central versus peripheral cortical
      perfusion intensity (1.36 vs. 0.60 cm/sec) and a significant loss of perfusion
      intensity in the posttransplantation period in the peripheral cortex from 1.06
      cm/sec in the first year to a minimum of 0.39 cm/sec in the 3- to 5-year
      interval, with stronger perfusion in longer surviving transplants: 0.71 cm/sec
      more than 9 years after transplantation. In the central cortex, a similar but
      less pronounced pattern could be demonstrated. A significant drop of parenchymal
      perfusion was found in patients with elevated serum creatinine (1.36 cm/sec in
      cases with normal and 0.82 cm/sec in those with elevated creatinine at the
      proximal cortical level). The perfusion ratio of the central 50% and the
      peripheral 50% shows marked changes over time: in the first year, the ratio was
      2.99, climbing to 5.56 at the 3- to 5-year interval and declining later on.
      CONCLUSIONS: Cortical tissue perfusion in renal transplants was quantified
      noninvasively from color Doppler signal data in an easily accomplishable manner.
      Renal transplants showed a marked decline in tissue perfusion after
      transplantation. Perfusion is significantly lower in transplant function loss
      with elevated serum creatinine.

PMID- 15973174
TI  - Outcome of untreated grade II rejection on solitary pancreas allograft biopsy
      specimens.
AB  - BACKGROUND: The most widely used grading scheme for acute pancreas allograft
      rejection grades biopsy specimens from 0 (normal) to V (severe rejection).
      Although the more advanced grades correlate strongly with immunologic graft loss,
      it is unclear how lesser grades impact graft outcome. The authors therefore
      report the outcomes of untreated grade II (minimal) rejection of solitary
      pancreas biopsy specimens. METHODS: The authors retrospectively analyzed all
      solitary pancreas transplants performed at the Mayo Clinic between January 2001
      and November 2002. The authors selected all patients who were found with grade II
      findings on biopsy. Whether patients underwent follow-up biopsies, what the
      results were, and graft survival at the end of the study period were then
      determined. RESULTS: A total of 88 pancreas transplants were performed; 20
      pancreas transplant recipients (23%) developed grade II (minimal) rejection and
      were followed for a mean of 22.8+/-8.7 months. Eighteen patients underwent biopsy
      for protocol purposes and two patients underwent clinically indicated biopsies.
      Of the patients who underwent biopsy as per protocol, 15 of the patients had a
      total of 25 follow-up biopsies: 10 were grade 0; 3 were grade I; and 10 were
      unchanged (grade II). Rejection in one patient progressed to grade III and in
      another patient to grade IV. The three patients who did not undergo repeat biopsy
      had a functioning allograft pancreas at the end of the study period. Of the two
      patients with grade II biopsy specimens obtained for clinical reasons, one had
      resolution of all inflammation noted on three follow-up biopsies, and the other
      patient did not undergo follow-up biopsy and died with a functioning graft.
      CONCLUSIONS: Grade II (minimal) rejection of solitary pancreas allograft rarely
      progresses to more severe degrees of inflammation. Morphologic findings in this
      category may not have unfavorable prognoses over a period of 2 years when
      untreated.

PMID- 15973176
TI  - Health-related quality of life after pancreatic islet transplantation: a
      longitudinal study.
AB  - BACKGROUND: Pancreatic islet transplantation (PIT) has proven effective in
      achieving insulin independence, but to date, the impact of PIT on health-related
      quality of life (HRQL) has not been studied. METHODS: Ten patients who have
      undergone PIT at our institution were administered three HRQL questionnaires: the
      Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a
      fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months
      after PIT. Responses were compared by analysis of variance and paired Student's t
      tests. RESULTS: Hypoglycemia Fear Survey responses demonstrated that hypoglycemia
      related anxiety and hypoglycemia-related behavior modification occurred less
      frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the
      hypoglycemia questionnaire were also significantly improved after PIT, from a
      median score of 156 points before transplantation to 55 points 3 months after PIT
      (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after
      PIT (P=0.04). The median scores of all SF-36 components also improved after PIT.
      No significant changes were seen in the fatigue symptoms as assessed by the
      fatigue questionnaire. CONCLUSION: PIT recipients have less anxiety about the
      symptoms and consequences of hypoglycemia. PIT recipients also indicate that
      their behavior requires significantly less modification to prevent or treat
      hypoglycemia after PIT compared with before PIT. Further investigation is needed
      to determine whether PIT improves generic measures of HRQL.

PMID- 15973175
TI  - Risk factors and outcomes of hypogammaglobulinemia after lung transplantation.
AB  - BACKGROUND: Hypogammaglobulinemia (HGG) frequently occurs after solid organ
      transplantation; however, the prevalence and implications of HGG after lung
      transplantation are not well defined. The authors aimed to define the prevalence,
      risk factors, and outcomes of patients with severe HGG after lung
      transplantation. METHODS.: The authors performed a retrospective cohort study of
      57 lung transplant recipients at their center. Quantitative total and subclass
      immunoglobulin (Ig) G levels were obtained from patients. RESULTS: Thirty-four
      (60%; 95% confidence interval [CI], 46%-72%) patients had low IgG levels (IgG
      <700 mg/dL); of these, eight (14%; 95% CI, 6%-26%) had severe HGG (IgG <400
      mg/dL). Female patients had a higher risk of severe HGG than male patients (25%
      vs. 0%, P=0.007), and patients who underwent transplantation for emphysema had a
      higher risk of severe HGG than others (P=0.04). Patients with bronchiolitis
      obliterans syndrome had a higher risk of severe HGG than those without (50% vs.
      10%, P=0.03). Severe HGG was associated with an increased risk of pneumonia
      (P=0.01) and worse survival (P=0.04) but with neither the incidence of
      cytomegalovirus disease (P=0.54) nor a subsequent diagnosis of bronchiolitis
      obliterans syndrome (P=0.70). CONCLUSIONS: The authors have documented a high
      prevalence of HGG after lung transplantation. Emphysema, female gender, and
      bronchiolitis obliterans syndrome are risk factors for severe HGG. Patients with
      severe HGG had a higher cumulative incidence of pneumonia and worse survival.
      Studies of the efficacy and safety of IgG supplementation after lung
      transplantation should be pursued.

PMID- 15973177
TI  - Assessment of factors determining graft size in transplant of cadaver kidneys
      from child donors.
AB  - BACKGROUND: Kidneys from child donors are very efficient at adapting to the
      recipient organism. This research aims to verify the size of kidney grafts from
      pediatric donors after transplant and to identify factors responsible for the
      size attained by these kidneys. Moreover, it aims to seek relationships between
      size and function of the transplanted pediatric kidney. METHODS: Seventy-seven
      renal transplants performed at least 6 months earlier, with cadaver donor 15
      years old or younger, had ultrasound measurements of the graft and renal function
      assessment. Potential factors for graft volume were analyzed using bivariate
      analysis, followed by multiple linear regression. RESULTS: After a follow up of
      4.2+/-3.3 years posttransplant, the grafts presented the following range of
      measures: length 10.61+/-1.13 cm, width 4.67+/-0.84 cm, and depth 4.76+/-0.99 cm.
      Graft volumes were 126.62+/-47.76 cm. Bivariate analysis showed that (1) age of
      both donor and recipient at transplantation; (2) sex of recipient; (3) occurrence
      of acute rejection episodes were statistically significant. After multivariate
      analysis, age and sex of recipients were the only significant factors influencing
      graft volume; child kidneys reached greater volumes when transplanted into adult
      and male individuals. Larger volume kidneys presented significantly more
      proteinuria. No difference was evident with regard to creatinine clearance values
      or urinary retinol binding protein among kidneys of differing sizes. CONCLUSIONS:
      The size of the recipient (age and sex) is the main factor responsible for
      volumes achieved by kidneys from pediatric donors. The volume attained by these
      kidneys demonstrated no relationship with glomerular or tubular function of the
      organ.

PMID- 15973178
TI  - Artificial neural network and tissue genotyping of hepatocellular carcinoma in
      liver-transplant recipients: prediction of recurrence.
AB  - BACKGROUND: Liver transplantation (LT) is the treatment of choice for early stage
      hepatocellular carcinoma (HCC) with excellent 5-year survival, with a recurrence
      rate after LT of 3.4%. An artificial neural network (ANN), combined with
      genotyping for microsatellite mutations/deletions (TM-GTP), was designed at the
      University of Pittsburgh to predict tumor recurrence with a discriminatory power
      of 85%. This study aims to validate the ANN/TM-GTP model on patients receiving
      transplants in a single center. METHODS: Nineteen patients with HCC underwent LT
      at our center between 1999 and 2002 (mean follow-up of 49.3 months). The ANN/TM
      GTP analysis was performed blindly to prognosticate the risk of HCC recurrence,
      which was then validated against the actual clinical outcomes. RESULTS: Nineteen
      patients received transplants. The primary diagnosis was hepatitis C (n=16),
      cryptogenic cirrhosis (n=2), and autoimmune hepatitis (n=1). ANN/TM-GTP was
      applied to all patients. The combination of ANN/TM-GTP predicted three patients
      to suffer recurrence of HCC. All three had HCC recurrence within 39 months (11,
      23, and 39 months) postLT and died. Fourteen patients were predicted not to have
      HCC recurrence, and none did. Two patients could not be classified and were
      termed indeterminate for recurrence. CONCLUSION: ANN/TM-GTP had a high
      discriminatory power (17/19, 89.5%) in our cohort, accurately predicting HCC
      recurrence.

PMID- 15973179
TI  - Reduced risk for molecular disease in patients with chronic myeloid leukemia
      after transplantation from a KIR-mismatched donor.
AB  - BACKGROUND: To examine how killer-cell immunoglobulin-like receptor (KIR) ligand
      incompatibilities effect molecular relapse (MR), we compared the occurrence of
      bcr-abl-positive reverse-transcriptase polymerase chain reaction (RT-PCR) results
      in 236 CML patients (pts) after human leukocyte antigen (HLA)-identical (n=158)
      (group 1), HLA class I antigen mismatched and KIR-ligand compatible (n=49) (group
      2), and HLA class I antigen mismatched and KIR-ligand incompatible (n=29) (group
      3) hematopoietic stem-cell transplantation. METHODS: We performed a retrospective
      single-center study. MR was evaluated using the real-time RT-PCR method for the
      detection of bcr-abl transcripts. RESULTS: In the first group, 133 of 158 (84%)
      pts were in the first chronic phase of CML, and the corresponding figures were 33
      of 49 (67%) pts in group 2 and 19 of 29 (64%) in group 3 (P<0.05). MR occurred in
      1 of 29 (3%) pts in group 3 compared with 62 of 158 (39%) pts in group 1 and in
      11 of 49 (22%) pts in group 2 (P<0.001). A hematologic relapse developed in 20 of
      158 (13%) pts in group 1, 2 of 49 (4%) pts in group 2, and in 0 of 29 (0%) pts in
      group 3 (P<0.05). Multivariate analysis confirmed that KIR mismatches are a
      strong independent predictor for the occurrence of MR after transplantation
      (P<0.02). The 5-year overall survival rate did not vary greatly between the three
      groups (67% in group 1, 52% in group 2, and 66% in group 3). CONCLUSIONS: These
      results suggest that KIR-ligand incompatibility is an important prognostic factor
      in the occurrence of MR after transplantation for CML.

PMID- 15973180
TI  - Low pretransplant bone-mineral density and rapid bone loss do not increase risk
      for avascular osteonecrosis after allogeneic hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Avascular osteonecrosis (AVN) is a serious complication of allogeneic
      stem cell transplantation (SCT). Graft-versus-host disease and its treatment with
      steroids are the main risk factors; underlying diagnosis, age and gender are
      further risk factors. It has been speculated that low baseline bone mineral
      density (BMD) is associated with AVN posttransplant. Furthermore, rapid bone loss
      with consecutive microarchitectural changes might prone patients to AVN. METHODS:
      In a single-center prospective cohort study, 255 patients undergoing allogeneic
      SCT for CML, AML, MDS, and ALL were followed for at least 5 years. We measured
      BMD (spine, femoral neck, total body) and body indices (body weight, body mass
      index, body composition determined by dual-energy x-ray absorptiometry) at
      baseline. Annual changes of BMD and body indices were prospectively observed for
      5 years. Incidence of hip AVN necessitating total arthroplasty (severe adverse
      event) was determined. Univariate and multifactorial nominal logistic as well as
      Cox proportional hazard analysis were performed. RESULTS: Severe adverse events
      occurred in nine patients (5-year cumulative incidence rate 6.9%). Baseline BMD
      and body indices were within normal limits. Rapid and intense bone loss occurred,
      especially during the first year, accompanied by loss of body and especially
      muscle mass. AVN occurrence was not associated with BMD or body indices at
      baseline neither with prospectively observed changes of BMD or body indices.
      CONCLUSIONS: AVN is a devastating frequent complication of allogeneous SCT.
      Allogeneous SCT is followed by dramatic changes in BMD and body composition.
      However, low BMD and rapid bone loss per se do not dispose patients to AVN
      occurrence.

PMID- 15973181
TI  - Improved outcomes after ABO-incompatible living-donor kidney transplantation
      after 4 weeks of treatment with mycophenolate mofetil.
AB  - Hyperacute humoral rejection of ABO-incompatible kidney transplants limits the
      application of this procedure. We evaluated the effect of 4-week treatment with
      mycophenolate mofetil (MMF), a compound that inhibits antibody production by B
      cells, before ABO-incompatible living-donor kidney transplantation with
      tacrolimus as the primary immunosuppressant. In contrast with cases without MMF
      pretreatment, we did not observe any graft loss caused by hyperacute humoral
      rejection in the 18 patients who received MMF. Overall, the incidence of adverse
      events was comparable in the MMF-treated and -untreated groups. The
      administration of MMF 4 weeks before kidney transplant effectively inhibits B
      cell function, suggesting a potential role for MMF in the prevention of humoral
      rejection.

PMID- 15973182
TI  - Detectable circulating antiendothelial cell antibodies in renal allograft
      recipients with C4d-positive acute rejection: a report of three cases.
AB  - It is suggested that non-HLA endothelial antigens may also cause C4d-positive
      acute rejection, but this is very rare. We report on three renal allograft
      recipients who developed C4d-positive acute rejection with detectable circulating
      antiendothelial cell antibodies (AECAs). All patients had severe dialysis
      dependent graft dysfunction. Histologic manifestations include neutrophils
      infiltration on peritubular capillaries and glomeruli. Endoarteritis can be seen
      in all the patients. Two patients lost grafts after the rescue therapy including
      immunoadsorption, mycophenolate mofetil with or without tacrolimus. The titer
      variation of AECAs might be associated with the graft outcome. In patients those
      who lost grafts, AECAs titer increased from 1:10 to 1:80 in one patient, and was
      kept positive during the treatment in the other patient. In the recovered
      patient, however, the titer became negative from 1:40. From our report, it
      appears that persisting circulating AECAs during the rescue treatment of C4d
      positive acute rejection may be associated with a poor outcome.

PMID- 15973183
TI  - Endovascular management of arterial conduit pseudoaneurysm after liver
      transplantation: a report of two cases.
AB  - We describe two cases of pseudoaneurysms in liver-transplant iliac artery
      conduits, which were successfully treated with endovascular stent grafting.

PMID- 15973184
TI  - Hemobilia secondary to a posttransplant lymphoma after liver transplantation.

PMID- 15973185
TI  - Laparoscopic inguinal hernia repair as a potential complicating factor in kidney
      transplantation.

PMID- 15973186
TI  - Recommendations for diagnosis of acute gastrointestinal graft-versus-host disease
      in the small intestine.

PMID- 15973187
TI  - Blood pressure and renal function after kidney donation from hypertensive living
      donors.

PMID- 15973189
TI  - Lack of evidence for ribavirin monotherapy efficacy on liver fibrosis in
      hepatitis C virus positive renal transplant patients.

PMID- 15973190
TI  - Islet transplantation in a recipient presenting the factor V Leiden mutation.

PMID- 15973193
TI  - Retraction.

PMID- 15973194
TI  - [Analysis of the eye's anterior segment with optical coherence tomography. Static
      and dynamic study].
AB  - PURPOSE: To study the biometric modifications of the anterior segment depending
      on accommodation and age. To try and define their possible applications in
      certain fields of anterior segment surgery, in particular in refractive implants.
      MATERIAL AND METHOD: Anterior chamber biometry can be very easily studied with
      1310-nm wavelength optical coherence tomography. The equipment has a fixation
      target that can be focused and defocused with negative lenses in order to
      stimulate natural accommodation. The human anterior chamber was therefore studied
      during accommodation. We studied 104 eyes of 56 patients aged between 7 and 82
      years. Refraction was between +5D and - 5D. A single operator carried out all the
      measurements. The anterior chamber's horizontal diameter, the anterior chamber's
      depth, the horizontal pupil diameter and the horizontal radius of curvature of
      the crystalline lens' anterior pole were measured unaccommodated or after
      stimulating accommodation. RESULTS: The different static or dynamic measurements
      were compared to ametropia, age and accommodation. At rest, the average AC
      diameter was 12.33 mm, the average AC depth was 3.11 mm and the average pupil
      diameter was 4.26 mm. On average, for 1 D of accommodation, the crystalline lens
      anterior pole moved forward by 30 microm. There was a 0.3-mm reduction in its
      radius of curvature and a 0.15-mm reduction in pupil diameter. Several other
      measurements are illustrated on graphs. CONCLUSIONS: The AC OCT is a user
      friendly instrument to evaluate the anterior segment and explore the anterior
      chamber (cornea, iris, crystalline lens, irido-corneal angle). The 1310-nm light
      wavelength is blocked by pigments preventing exploration behind the iris.
      However, the AC OCT is capable of providing good-quality images and a better
      visualization of the anatomical relationships of the anterior segment, even
      behind an opaque cornea.

PMID- 15973195
TI  - [Comparison of two surgical techniques for the treatment of superior oblique
      palsy].
AB  - AIM: To compare two surgical techniques for the treatment of superior oblique
      palsy. PATIENTS AND METHODS: Retrospective study involving 32 patients operated
      on at the Rouen Teaching Hospital for superior oblique palsy. Group 1 patients
      were treated by surgical reinforcement of the superior oblique muscle and group 2
      patients were treated by surgical loosening (or weakening) of the antagonist
      muscles. One-year follow-up explored head tilt, diplopia, vertical deviation and
      cyclotorsion. RESULTS: Functional results (presence of diplopia or stiff neck)
      were positive in both groups but better in group 1. Only 12.5% of patients
      required a second operation. Cyclotorsion amounted to less than 2% in group 1 and
      was still greater than 8% in group 2; on the other hand, vertical deviation had
      improved more in group 2, where it decreased to 2.1 diopters versus 3.1 in group
      1. DISCUSSION: and conclusion: Only reinforcing the superior oblique adequately
      corrects cyclotorsion, which is the main cause of asthenopia and diplopia,
      despite an often insufficient height correction that is otherwise clinically well
      tolerated. We suggest reinforcing the superior oblique as a first intent rather
      than weakening hyperactive muscles, and in case of excessive postoperative
      height, we would carry out additional treatment of one of the hyperactive muscles
      later.

PMID- 15973196
TI  - [Retinal detachment associated with giant retinal tear: surgical procedures and
      results of the perfluorocarbon liquid-silicone oil exchange with scleral
      buckling].
AB  - INTRODUCTION: Anatomical and functional results of the treatment of retinal
      detachment associated with giant retinal tear have been markedly improved with
      the development of the vitrectomy procedure and especially the use of
      perfluorocarbon liquids. In this study, we report treatment results of retinal
      detachment associated with giant tear in 17 patients. MATERIALS AND METHODS: Our
      study included 17 patients (17 eyes), aged between 18 and 61 years, with retinal
      detachment associated with giant retinal tear. The size of the tear was between
      90 degrees and 220 degrees . Proliferative vitreoretinopathy grade C was present
      in two eyes. Preoperative visual acuity ranged between 40/50 and light
      perception. All patients underwent scleral buckling, vitrectomy, perfluorocarbon
      liquid injection to flatten the retina, endophotocoagulation, cryoapplication and
      temporary silicone oil tamponade. RESULTS: Mean follow-up was 20 months +/- 16.
      Recurrent retinal detachment occurred in five eyes under silicone oil and in two
      eyes after its removal. Anatomical success at final follow-up was obtained in 14
      eyes (82.3%). Visual acuity improved in all cases with anatomical success in all
      but one. The most frequent postoperative complications were cataract in 10 cases
      among 12 phakic eyes and ocular hypertension in four cases. CONCLUSION:
      Vitrectomy with internal silicone oil tamponade improves the anatomical and
      functional prognosis of retinal detachment associated with giant retinal tear.
      Recurrent retinal detachment is usually due to relapsing proliferative
      vitreoretinopathy. The most frequent postoperative complications remain lens
      opacification and ocular hypertension.

PMID- 15973197
TI  - [Low-vision rehabilitation of age-related macular degeneration patients with
      retrofoveal choroidal new-vessels treated with photodynamic therapy with
      verteporfin].
AB  - PURPOSE: To demonstrate the rehabilitation benefit and immediate optical
      magnification and electronic equipment advantage in an age-related macular
      degeneration population with retrofoveal choroidal new-vessels treated by
      photodynamic therapy using Visudyne. PATIENTS AND METHODS: Sixty seven
      consecutive patients with retrofoveal choroidal new-vessels treated by
      Photodynamic Therapy using Visudyne were referred to an orthoptist for low-vision
      rehabilitation. The criteria investigated for this study were: long distance
      visual acuity, reading ability, contrast sensitivity, (before treatment and
      during post-treatment examinations), and fixation localization and optical
      equipment model. RESULTS: This study showed and studied visual acuity variations,
      mostly for patients with good visual acuity at inclusion. Contrast sensitivity
      stayed more or less the same. Retinal fixation was foveolar most of the time
      (68.7%). Optical or electronic devices for low-vision patients are numerous and
      video systems were the most currently used among our population. 62.7% des
      patients had low-vision rehabilitation with optic aids. DISCUSSION AND
      CONCLUSION: This study threw light on patient optic aids which must be prescribed
      according to his needs and difficulties, without delay. This equipment will then
      be readapted at each stage of the patient evolution. PDT treatment gives an
      important role to low-vision rehabilitation associated with optic magnification
      aids.

PMID- 15973198
TI  - [Proliferative diabetic retinopathy: vitreo-retinal complications are often
      related to insufficient retinal photocoagulation].
AB  - INTRODUCTION: Panretinal photocoagulation proved to be effective in preventing
      complications related to vasoproliferative diabetic retinopathy. Surgery is most
      often a last resort in cases of recurrent or persistent vitreous hemorrhage or
      retinal detachment. The aim of our study is to point out that eyes requiring
      surgery for complications related to vasoproliferative diabetic retinopathy are
      often insufficiently photocoagulated. PATIENTS AND METHODS: Retrospective
      analysis of operating protocols and surgical results for a series of 39 eyes of
      36 patients with complications of vasoproliferative diabetic retinopathy.
      RESULTS: The mean age at the intervention was 57 years. Eighty-five percent of
      the eyes had a vitreous hemorrhage, 17% a retinal detachment. Eighty-five percent
      of the eyes had undergone a partial retinal photocoagulation before surgery. All
      eyes underwent a vitrectomy with segmentation of fibrovascular membranes. In 85%
      of the eyes studied, endolaser photocoagulation was necessary, sometimes even in
      the mid-periphery. After 39+/-26 months of postoperative follow-up, 97% of eyes
      showed improvement of the anatomical state of the retina and improvement or
      stabilization of visual acuity. CONCLUSION: Our results confirm the benefit of
      vitreoretinal surgery in complications related to vasoproliferative diabetic
      retinopathy. Moreover, it should be emphasized that complications requiring
      surgery often result from incomplete preoperative photocoagulation. To be
      effective, photocoagulation has to destroy more than 35% and up to 50% of
      photoreceptors. An intraoperative laser extension can reduce the risk of regrowth
      of fibrovascular membranes.

PMID- 15973199
TI  - [Association study between diabetic retinopathy and aldose reductase gene
      polymorphism in Tunisians].
AB  - INTRODUCTION: Aldose reductase (ALR2), the enzyme of the polyol pathway, may play
      an important role in the pathogenesis of diabetic microvascular complications,
      namely diabetic retinopathy. The study aimed to determine whether the aldose
      reductase gene is involved in diabetic retinopathy in the Tunisian population.
      MATERIAL: and methods: A case-control study was conducted in 47 type 2 diabetic
      patients who have diabetic retinopathy and 28 diabetic patients without diabetic
      retinopathy in spite of diabetes lasting for more than 5 years and over 10 years
      in 13 cases. We investigated the association between the (CA)n polymorphism
      located at 2.1 kb upstream of the transcription start site of ALR2 and diabetic
      retinopathy. The distribution of genotypes and alleles was compared between cases
      and controls by chi2 test using Epi info software. RESULTS: Genotyping of the two
      groups did not demonstrate any association between the alleles of this marker and
      diabetic retinopathy in the Tunisian population studied. DISCUSSION: An
      association between one of the alleles (Z - 2) of this microsatellite and
      diabetic retinopathy was identified in Chinese and Japanese patients with type 2
      diabetes. Discordant results were obtained for the different populations studied.
      The lack of an association between diabetic retinopathy and ALR2 alleles
      indicates that the ALR2 gene is not a genetic marker of predisposition to
      diabetic retinopathy for type 2 diabetic patients in the Tunisian population
      studied.

PMID- 15973200
TI  - [Sickle cell beta-thalassemia leading to serious ischemic retinopathy: a study of
      18 patients in Abidjan].
AB  - The authors in this study intended to demonstrate that S-beta thalassemia can
      lead to severe ocular hemorrhagic risks, as is true of the sickle cell form. Both
      forms are also comparable in terms of the risk of aseptic necrosis of the femoral
      head. Out of the 18 patients studied, 13 (72.2%) had sickle cell retinopathy.
      Three of 13 patients had already developed new vessels and risked intravitreous
      hemorrhage. The authors recommend that more vigilance be mounted for the
      detection of S-beta thalassemia so as to benefit from rigorous and systematic
      follow-up and early treatment. Retinal argon laser photocoagulation is only
      effective if a clear diagnosis is made early.

PMID- 15973201
TI  - [Computer-assisted diagnosis and therapy for glaucoma].
AB  - Boolean algebra, or combinatory analysis and their related computer routines, can
      provide invaluable help in resolving classic diagnostic problems. However complex
      each case may be, the diagnosis is always made from a finite set of data, and the
      fundamental problem is thus how to exploit this data. Invention no longer has a
      place in ascertaining a diagnosis. Traditional ways of reasoning are numerous,
      personal, and fragile, but fortunately redundant. They may give rise to four
      types of error: omission or mistake (an error of judgment), either during the
      semiotic or the dialectic stages. Whereas the physiological capacity of the human
      brain and memory only enables it to make a limited number of hypotheses
      concerning certain aspects of glaucoma, computer programs can take the total
      number of hypotheses into account, i.e., 3000. For every input the program
      explores each of the 3,000 items, thus eliminating the four types of error. The
      probabilistic nature of data, which compromises the confidence one can have in
      conclusions resulting from such complex reasoning, is treated by the adjusted
      probabilities. The use of such diagnostic aids, whose thesaurus is updated
      regularly, is reserved for ophthalmologists, the only authority capable of
      assessing the pertinence of the computer responses. Consequently, the specialist
      can rest assured that the patient has benefited from the most comprehensive and
      updated knowledge in medical science.

PMID- 15973202
TI  - [Arteriovenous malformation of the brain revealed through a visual blur and
      Adie's pupil].
AB  - INTRODUCTION: Arteriovenous malformations of the brain (BAVMs) are a relatively
      rare group involving intracranial vascular lesions (telangiectasia, cavernous
      malformation, venous anomaly). We report the case of a patient who presented an
      atypical visual symptomatology revealing a BAVM. OBSERVATION: A 48-year-old woman
      consulted for a recent bilateral visual blur. In darkness, discrete anisocoria
      appeared on the left eye. At the biomicroscopy light examination, we found
      areflexic semi-mydriasis (direct and consensual) on the left eye; the light
      reflex (direct and consensual) on the right eye was normal. During the
      accommodative reflex test the left pupil contracted. We propose the diagnosis of
      Adie's pupil, which was confirmed by the pilocarpine test (0.125%). We decided to
      examine the visual field because the symptomatology of the visual blur remained
      unexplained. The visual field showed a left homonymous inferior lateral scotoma.
      MRI showed a right occipital arteriovenous malformation. DISCUSSION: A quick
      examination could confuse painless anisocoria with a compression of the IIIrd
      intrinsic left nerve. This recent scotoma revealed BAVM progression. The natural
      history of BAVMs shows that the essential risk of these injuries is the onset of
      an intracranial hemorrhage. To reach a radical therapeutic decision, a cerebral
      arteriography clarifying the afferent and efferent vascularity of the nidus was
      carried out. CONCLUSION: This case is original in that it associates the
      concomitant discovery of a BAVM and Adie's pupil. Symptomatic BAVMs are extremely
      serious. Planning their treatment requires multidisciplinary cooperation in order
      to reduce the risk of mortality.

PMID- 15973203
TI  - [Progressive essential iris atrophy associated with chronic cystoid macular
      edema].
AB  - We describe a first clinical case associating progressive essential iris atrophy
      (iridocorneal epithelial syndrome, or ICE syndrome) and chronic cystoid macular
      edema. The clinical presentation and therapeutic progression suggest an
      inflammatory retinal barrier rupture as seen in Irvine-Gass syndromes. OCT or
      angiographic exploration should be systematically performed in cases of ICE
      syndrome to detect a subclinical macular edema.

PMID- 15973204
TI  - [Use of topical cutaneous N-acetylcysteine in the treatment of major bilateral
      ectropion in an infant with lamellar ichthyosis].
AB  - PURPOSE: To report for the first time bilateral ectropion treatment in an infant
      with severe lamellar ichthyosis associating N-acetylcysteine applied directly to
      the skin and oral acitretin. METHODS: An 8-week-old male child with major
      bilateral ectropion due to lamellar ichthyosis was given treatment associating
      oral acitretin (Soriatane) and topical N-acetylcysteine. Though the precorneal
      tear film quality could be maintained, after 1 month of initial treatment with
      acitretin only, bilateral upper eyelid ectropion remained threatening for the
      child's cornea. The adjunction of topical N-acetylcysteine enabled a complete
      regression of ectropion. No complementary surgery was needed and the eyelids
      remained well positioned. CONCLUSION: Topical N-acetylcysteine has been proved to
      have an antiproliferative effect on keratinocytes in vitro and in vivo. It may be
      useful in the treatment of major forms of ectropion in children with lamellar
      ichthyosis. Its association with conventional acitretin treatment may prevent
      unnecessary surgery.

PMID- 15973206
TI  - [Microsurgery of canalicular stenosis].
AB  - The microsurgical treatment of canalicular stenosis is indicated in localized
      stenosis. The goal is to restore lacrymal mucosa continuity in order to re
      establish spontaneous lacrymal drainage. Stenosis located close to the puncti can
      be reached by the direct approach, those close to the lacrymal sac require an
      approach via the common canaliculus. The surgical indications and techniques are
      developed, with particular attention given to common canaliculus repair and the
      new surgical approach to reach it.

PMID- 15973207
TI  - [Surgery of lacrimal secretion].
AB  - Surgical treatment of lacrimal secretion consists in reducing the product of
      tears in the lacrimal gland. Denervation of the lacrimal gland was described long
      ago by Whitwell and remains in current use. Recently, injection of botulinum
      toxin into the lacrimal gland was successfully carried out. In our department, we
      have been developing lacrimal duct orifice cauterization for several years. We
      discuss these three methods and develop the latter in greater detail.

PMID- 15973208
TI  - [Endoscopic diagnosis of the lacrimal drainage system].
AB  - Endoscopic study of the lacrimal drainage system is the only way to directly
      observe the lacrimal sector of the lacrimal drainage system. The first
      experiments on this subject date from 1979. Recent technological progress has
      allowed us to test the latest instruments. These experiments have demonstrated
      the unquestionable progress of endoscopes and their potential contribution to
      diagnosing lacrimal pathology. However, certain factors still limit their
      everyday use. Image improvements and low cost will no doubt facilitate its
      integration in the diagnosis and therapy of the lacrimal drainage system.

PMID- 15973209
TI  - [Mastering endonasal dacryocystorhinostomy].
AB  - A persistent, symptomatic lacrimal duct stenosis is treated by
      dacryocystorhinostomy (DCR), with external (EX) or endonasal (EN) access. The
      basic indication is the same in all cases and either route can be used. The EX
      route seems better in terms of speed of surgery, learning curve and cost. It is
      logical to use the external route to treat the disorder when it is associated
      with a lacrimal sac diverticulum, an irreducible stenosis of the union canal, or
      a canthopexy. The EN route has been shown to be worth consideration whenever
      there is a nasal sinus disorder that can be repaired at the same time. Moreover,
      it is indicated in a rare case of lacrimal abscess that cannot be treated
      medically, where the risk of scarring would contraindicate standard surgery, or
      when DCR is recurrent. A series of prospective randomized studies is needed to
      determine whether the route materially influences the outcome. Until then, it is
      best to have both methods available for an unbiased case-by-case decision.

PMID- 15973210
TI  - [Use of mitomycin C (MMC) for dacryocystorhinostomy interventions].
AB  - Mitomycin C (MMC) has been described as having a positive effect in different
      types of dacryocystorhinostomy (DCR) surgery such as external DCR, endonasal and
      transcanalicular DCR. MMC, an antineoplastic antibiotic, acts as an alkylating
      agent by inhibiting DNA, RNA and protein synthesis. Topical use of MMC can
      modulate the scarring process, which is useful in glaucoma surgery and pterygium
      excision. In DCR, MMC is also useful because it reduces the scarring process and
      thus prevents the occlusion of the osteotomy site related to the fibroblast
      activity. An increase in the success rate for long-term results has been observed
      by different authors, resulting from a larger osteotomy size as well as a
      decrease in the density and cellularity of the mucosa. No complications have been
      seen with topical use of MMC.

PMID- 15973211
TI  - [Tortuous vascular structures and chorioretinal folds on the severely
      hypermetropic eye (+ 4,50)].

PMID- 15973212
TI  - [Colorectal carcinoma metastasis in livers infected with hepatitis B or C virus].
AB  - AIM: Metastases from colorectal cancers rarely occur in injured livers, however
      in western countries this phenomenon has not been investigated in patients with
      various forms of chronic hepatitis. Therefore in this study we evaluated the
      incidence of synchronous hepatic metastases of colorectal carcinomas in patients
      with hepatitis B (HBV) or C (HBC) infection. METHODS: Six hundred and thirty
      patients undergoing surgical treatment for colorectal carcinomas were analysed:
      the clinicopathological data of 87 patients with HBV or HCV infection (there were
      29 patients with hepatitis C infection and 58 with hepatitis B infection) were
      compared to those of 543 non infected patients. RESULTS: Patients distribution
      was similar in both groups in terms of gender, age, type of operative procedures
      performed, histological grading and lymph node metastases. Stage I, II or III
      tumours were similarly represented in non infected and infected patients, while
      stage IV tumours were 33.1% in the non infection group and 17.2% in the infection
      group (P < 0.001). At the time of surgery, synchronous extrahepatic metastases
      were present in 14.9% of non infected patients and 15% of infected patients,
      while synchronous hepatic metastases were found in 32% and 17.2% of patients
      respectively (P < 0.01). CONCLUSIONS: Results of our study show that synchronous
      hepatic metastases of colorectal cancers are less frequently observed in chronic
      HBV or HCV infected patients than in non infected patients, while the incidence
      of extrahepatic metastases is comparable in both groups, suggesting that virus
      related mechanisms and specific liver mediated immunity may have a protective
      role against neoplastic cell colonization of the liver.

PMID- 15973213
TI  - [Parathyroidectomy: bilateral exploration of the neck vs minimally invasive
      radioguided treatment].
AB  - AIM: In the therapy of primary hyperparathyroidism, the first surgical
      intervention, if efficacious, can remarkably reduce the incidence of persistence
      and relapses which are approximately about 5%. At present, the surgical approach
      of choice should involve the bilateral exploration of the neck. METHODS: In the
      light of the high sensibility (91%) and specificity (98.8%) in the localization
      of parathyroid adenomas obtained by the parathyroid 99mTc-MIBI scintigraphy, we
      submitted, prospective and at random, between January 2001 and July 2004, 69
      patients with primary hyperparathyroidism, to a conventional surgical treatment
      (bilateral exploration of the neck: 35 patients) or minimally-invasive approach
      (minimally invasive radioguided parathyroidectomy: 34 patients). This method
      consists of the injection of 50 mCi of 99mTc Sestamibi 2 h before the operation
      and the execution of parathyroid scintigraphy. When the adenoma is evident, we
      perform an incision of about 4 cm in the neck, 2 cm over the jugulum and the
      surgical dissection is guided by a probe showing the emission of gamma rays.
      RESULTS: The parameters considered in order to compare the 2 groups, i.e.
      operating time, hospital stay and time of recovery were reduced in a significant
      way in the group submitted to the minimally invasive radioguided
      parathyroidectomy (MIRP). There were no complications in the 2 groups. In the
      follow-up we did not observe cases of persistence or relapses. CONCLUSIONS:
      Therefore, we can confirm that the minimally invasive radioguided
      parathyroidectomy is a safe and efficacious method as well as the bilateral
      exploration of the neck. Moreover, cost reduction may convince many surgeons to
      consider MIRP the <<gold standard>> in the management of primary
      hyperparathyroidism.

PMID- 15973214
TI  - [New view in the mammary asymmetry treatments].
AB  - AIM: Breast asymmetry is a huge chapter of breast abnormalities. Surgical therapy
      is the exclusive one. The breast of women can vary in shape, volume and position,
      thus creating esthetic, social and psychological problems. METHODS: We classified
      breast asymmetry into 6 categories and then we treated them with different
      surgical techniques: reduction mammaplasty according to Planas; augmentation
      mammaplasty with prosthesis; grafts or both; ultimately mamma-prosthesis
      (association of mastopexy and prosthesis). We obtained satisfactory esthetic
      results often with one surgery procedure. Rarely we performed 2 or more
      procedures of symmetry. We treated 77 patients suffering from breast asymmetry.
      We excluded in this study the giant-mammary asymmetry (anomaly determined by
      severe and asymmetric mammary hypertrophy). RESULTS: We found a low number of
      complications at short and long term. These results are likely due to the ability
      of the surgeon in the appropriated preoperative evaluation of the patients and of
      their expectancy and correct surgical techniques. CONCLUSIONS: We tried to obtain
      3 results: shape and position of the sick breast as same as possible to the
      contralateral breast and less evident scars located in hidden regions.

PMID- 15973216
TI  - [Pancreatic fistula after pancreaticoduodenectomy: risk factors and treatment].
AB  - AIM: Operative mortality rates after pancreaticoduodenectomy (PD) have decreased
      dramatically over the past 3 decades and recent series have reported no
      mortality. Nevertheless pancreatic leakage remains the major cause of morbidity
      with incidences varying between 6-16%. The aim of the study is to analyze the
      main etiopatogenetic factors and the treatment of this complication in the
      literature and, retrospectively, in own experience. METHODS: At the Clinical
      Surgery of the University of Genoa, from 1991 to 1995, and then at the General
      Surgery Department of the Hospitals of Bordighera and Imperia, between 1995 and
      2003, 30 PD were completed; there were 20 males (66.6%) and 10 females (33.3%),
      the average age being 64.6 years (range 50-81). Indications for surgery were
      pancreatic head adenocarcinoma (70%), ampullary adenocarcinoma (16.6%), duodenal
      adenocarcinoma (6.6%) and chronic pancreatitis (6.6%).The personal method of
      reconstruction after PD consisting of a double Roux-en-Y on the same jejunal loop
      without interruption of the mesentery and a third anatomical Roux-en-Y to
      reconstitute the alimentary tract. The gastric stump was anastomosed with the
      jejunum as a Billroth II-type reconstruction in older patients. RESULTS: The mean
      hospital stay was 15 days (range 10-40), the operative time 397 min (range 295
      500) and transfusion of red blood cells 0.2 (range 0-3). The incidence of
      perioperative mortality was 0; pancreaticojejunostomy leakage occurred in 3
      patients (10%); one of this died 48 days after surgery for bleeding. CONCLUSIONS:
      the level of pancreatic fibrosis and diameter of main pancreatic duct are the
      more important risk factors for complications after PD. Nowadays
      pancreaticojejunostomy remains the standard technique; pancreaticogastrostomy,
      occlusion of the pancreatic duct and two-stage pancreaticojejunostomy must be
      reserved to selected cases. The majority of pancreatic fistulas are uncomplicated
      and heal with conservative treatment. The skills of the interventional radiology
      team provide expert management of these complications, speeding recovery times
      and minimizing morbidity. If surgical re-exploration is necessary, an early
      completion pancreatectomy may maximize survival.

PMID- 15973217
TI  - 16-year follow-up study of Vena Cava Filters Group.
AB  - AIM: The prevalence of venous thromboembolic disease (VTED) is between 0.05% and
      0.1% whereas its incidence is approximately 0.1%. Out of 100 patients with deep
      vein thrombosis (DVT), 5 will develop clinically serious pulmonary embolism (PE),
      one of which will be fatal. It is well known from the literature that surgical
      interventions carried out without antithrombotic prophylaxis have a 30% incidence
      of DVT, which can be halved with adequate prophylaxis. The aim of this study is
      to evaluate the immediate, middle- and long-term complications of caval filters
      by identifying any of the problems connected with or independent of the presence
      of the filter, also in relation to international literature data. METHODS: In
      view of the evolution of VTED surgical prevention methods, we have analyzed our
      case record composed of 821 patients (October 1984-October 2002), treated with
      different surgical solutions for VTED, with indications for the placement of 634
      caval filters. RESULTS: The 30-day follow-up of all the 634 filters placed (100%)
      shows no mortality from the procedure and any of its immediate complications. The
      middle-term follow-up (from 1 month to 5 years) of 361 filters (57%) shows 0.55%
      mortality from PE while the long-term follow-up (5-16 years) of 105 filters (17%)
      shows a percentage decrease in all complications and no mortality from PE. The
      results also show a progressive annual decrease in the number of filters placed.
      CONCLUSIONS: The lower incidence of complications, compared to that reported in
      the literature, can be attributed to both improved operator dexterity in the
      placement of the filter and correct management of the complications. The lower
      number of filters used can be explained by improved therapeutic possibilities
      with new low molecular weight heparins (LMWH) and by current diagnostic as well
      as instrumental and biochemical monitoring methodologies.

PMID- 15973218
TI  - [Video-assisted trans-umbilical appendectomy: an effective and safe alternative
      in non-complicated appendicitis].

PMID- 15973219
TI  - Evaluation of N parameter in the staging of non-small cell lung cancer: role of
      CT and PET.
AB  - PURPOSE: To determine diagnostic accuracy of CT and FDG-PET for the evaluation of
      N status in non-small cell lung cancer. MATERIALS AND METHODS: Thirty-eight CT
      scans and PET scans of patients with non small-cell lung cancer were
      retrospectively reviewed. The data of the noninvasive techniques about N status
      were compared with the pathology findings obtained by standard lymphadenectomy.
      RESULTS: The CT results were concordant with surgery in 24 out of 38 cases (63%);
      in discordant cases CT understaged 8 patients and overstaged 6. The PET images
      were concordant with surgery in 29 cases (76%); of the remaining 9, PET
      understaged 5 cases and overstaged 4. Concerning the N parameter, CT had a
      sensitivity of 42.8% and a specificity of 83.3%, while PET had a sensitivity of
      71.4% and a specificity of 91.6%. CONCLUSIONS: In our experience the diagnostic
      accuracy of PET is superior to that of CT, in agreement with the most important
      studies in the literature. On only one occasion did PET fail to differentiate
      between hilar uptake (N1) and the central primary tumour, an area in which CT
      provided more precise anatomic details. Nonetheless, we believe that PET should
      be performed in all patients affected by lung cancer, with the only exception of
      patients shown to be not suitable for surgery after CT examination.

PMID- 15973220
TI  - High resolution CT (HRCT) of the lung in adults. Defining the limits between
      normal and pathologic findings.
AB  - Under normal conditions, HRCT shows secondary lobule structures and allows for a
      precise evaluation, with inspiratory and expiratory scans, of central airways
      dimensions, lung area and parenchymal density. Frequently, asymptomatic smokers
      with normal lung function tests, present with mild abnormalities not visible at
      chest X-ray: bronchial thickening, bronchiolectasis, respiratory bronchiolitis
      and centrilobular or paraseptal emphysema. In the elderly, HRCT studies often
      show borderline findings such as age-related tracheo-bronchial calcifications and
      emphasise the progressive increase in the bronchoarterial ratio. Another frequent
      finding is expiratory air trapping, which can be associated with a variety of
      lung diseases, but can also represent a physiologic and temporary finding, during
      an episode of sub-clinical bronchospasm or related to local variation of
      bronchiolar dynamic compliance. The knowledge of the boundaries between normality
      and pathology is an essential prerequisite for the correct interpretation HRCT
      findings.

PMID- 15973221
TI  - Differential diagnosis between usual interstitial pneumonia (UIP) and nonspecific
      interstitial pneumonia (NSIP) assessed by high-resolution computed tomography
      (HRCT).
AB  - PURPOSE: The aim of this study was to assess the accuracy of high-resolution CT
      in the differential diagnosis between UIP and NSIP, and the correlations with
      histological and functional findings. MATERIALS AND METHODS: Patients underwent
      thin-collimation spiral CT (1 mm), with 10-mm interval. Pulmonary function was
      assessed with a pneumotacograph and body plethysmograph connected with a computer
      for data analysis. Three pathologists, blinded to the clinical and functional
      data, provided a histological diagnosis based on established criteria reported in
      the literature. The study group only included patients with a histological
      diagnosis of either UIP or NSIP. RESULTS: We achieved a correct diagnosis of NSIP
      in 86.6% of cases (76.4% sensitivity; 84.6% specificity), whereas UIP was
      correctly diagnosed in 73.3% of cases (84.6% sensitivity; 76.5% specificity). An
      80% agreement was achieved between the HRCT and histological findings in the
      whole case series (73% sensitivity, 87% specificity, p<0.01). CONCLUSIONS: The
      most important finding of our study was that a ground glass appearance equal to
      or greater than 15% is highly suggestive of NSIP. Therefore, our results could be
      useful to confirm a suggested diagnosis of NSIP.

PMID- 15973222
TI  - Magnetic Resonance angiography of the pulmonary veins before and after
      radiofrequency ablation for atrial fibrillation.
AB  - PURPOSE: To study the usefulness of magnetic resonance angiography (MRA) in
      imaging of the pulmonary veins (PV) before and after radiofrequency ablation
      procedures in patients with atrial fibrillation. MATERIALS AND METHODS: Between
      July 2002 and April 2003, 50 patients with atrial fibrillation underwent MRA
      prior to ablation; 18 patients also underwent post-procedure MRA. Images were
      acquired with 3D-spoiled gradient echo sequences after intravenous administration
      of the paramagnetic contrast medium gadopentetate dimeglumine; an automatic
      triggering device was used to start the angiographic sequence (Smartprep, General
      Electric Medical Systems). Postprocessing was performed with maximum intensity
      projection (MIP) and virtual endoscopy (VE) software (Navigator, GEMS). RESULTS:
      The venoatrial junction was visualised with MRA VE in 49 of 50 patients (98.0%).
      Twenty-seven patients out of 49 (55.1%) had two PV ostia on both sides, 13
      (26.5%) had two right ostia and a single common left ostium, 5 (10.2%) had
      supernumerary PV and 4 (8.2%) had both a supernumerary right PV and a single
      common left ostium. Flythrough navigation showed the number and spatial
      arrangement of second-order PV branches in 48 out of 49 patients (98.0%). In
      postablation examinations, mild stenosis was detected with MIP and VE in 17 out
      of 83 PV examined (20.5%). CONCLUSIONS: This study confirms the clinical value of
      magnetic resonance imaging for visualising PV ostia in patients undergoing
      radiofrequency ablation for atrial fibrillation. Before the ablation procedure,
      MRA allows an accurate evaluation of PV number, shape and size; after the
      procedure, MRA is useful in screening for post-ablation stenosis and describing
      the location and severity of stenosis when present.

PMID- 15973223
TI  - Non-invasive assessment of coronary artery stent patency with multislice CT:
      preliminary experience.
AB  - PURPOSE: To evaluate the diagnostic accuracy of multislice computed tomography
      coronary angiography (MSCT-CA) in the detection of in-stent restenosis. MATERIALS
      AND METHODS: Forty-two patients (33 male, 9 female, mean age 58+/-8 years)
      previously subjected to percutaneous implantation of coronary stent with
      suspected in-stent restenosis, underwent a 16-row MSCT (Sensation 16, Siemens)
      examination. The average time between stent implantation and MSCT-CA was 7.4+/
      5.3 months. The following scan parameters were used: collimation 16x0.75 mm,
      rotation time 0.42 s, feed 3.0 mm/rot., kV 120, mAs 500. After administration of
      iodinated contrast material (Iomeprol 400 mgI/ml, 100 ml at 4 ml/s) and bolus
      chaser (40 ml of saline at 4 ml/s) the scan was completed in <20 s. All segments
      with a stent were assessed by two observers in consensus and were graded
      according to the following scheme: patent stent, in-stent intimal hyperplasia
      (IIH) (lumen reduction <50%), in-stent restenosis (ISR) (=/>50%), in-stent
      occlusion (ISO) (100%). Consensus reading was compared with coronary angiography.
      RESULTS: Forty-seven stents were assessed (16 in the right coronary artery; 4 in
      the left main; 22 in the left anterior descending; 5 in the circumflex). In 7
      (17%) stents there was ISR (3) or ISO (4), and in 4 (10%) stents there was IIH.
      The sensitivity and negative predictive values for the detection of ISO were 80%
      and 98%, respectively, while for the detection of ISR+ISO they were 50% and 89%,
      respectively. CONCLUSIONS: Although the results are encouraging, the follow-up of
      stent patency with MSCT-CA does not show a diagnostic accuracy suitable for
      clinical implementation.

PMID- 15973224
TI  - Endoscopic ultrasound and Computed Tomography in the diagnosis, locoregional
      staging and assessment of vascular infiltration of pancreatic carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of colour
      Doppler Endoscopic Ultrasonography (EUS), in the detection, loco-regional staging
      and assessment of vascular infiltration in pancreatic carcinoma, and to compare
      the results with those obtained by Computed Tomography (CT). MATERIALS AND
      METHODS: A series of 57 patients with diagnosed or suspected pancreatic carcinoma
      was retrospectively analysed. All patients underwent EUS and thin-slice (< 5 mm)
      spiral dynamic CT. The final diagnosis (carcinoma in 37 patients and benign
      lesion in 20) was obtained by laparotomy in 21 patients, fine-needle aspiration
      cytology (FNAC) in 17, and follow-up in 19. RESULTS: The specificity and
      sensitivity for the diagnosis of malignancy were respectively 45% and 92% for EUS
      and 45% and 89% for CT, with an accuracy of 75% for EUS (p <0.05) and 74% for CT
      (p = 0.07). The specificity and sensitivity for the diagnosis of loco-regional
      nodal metastases were both 100% for EUS. The specificity and sensitivity for the
      diagnosis of vascular infiltration were 100% and 94% for EUS and 100% and 44% for
      CT, giving a diagnostic accuracy of 97% for EUS vs 74% for CT (p <0.001).
      CONCLUSIONS: EUS proved to be more sensitive and specific than CT in the loco
      regional staging of pancreatic carcinoma. Its diagnostic accuracy is especially
      high in assessing vascular infiltration and loco-regional nodal metastases. CT
      still remains the examination of choice for staging pancreatic carcinoma and for
      assessing its resectability as it affords a panoramic view and ability to rule
      out distant metastases. Candidates to resection should all be examined by EUS,
      as, due to its high accuracy in loco-regional staging and assessing vascular
      infiltration, it might allow a large proportion of patients to be spared the
      operation.

PMID- 15973226
TI  - Abdominal radiography findings in small bowel anastomoses with V-BAR.
AB  - PURPOSE: The aim of the present paper is to describe the normal radiological
      findings and the fragmentation time of the VALTRAC BAR (V-BAR). MATERIALS AND
      METHODS: Ten cases of Roux-en-Y jejuno-jejunostomy with anastomosis with a n.25
      Valtrac ring for gastric cancer were followed up during the postoperative period
      by plain abdominal X-ray examination. RESULTS: Abdominal X-ray examination showed
      V-BAR fragmentation between day 14 and 21 after surgery. In one case only did
      fragmentation fail and the V-BAR migrated resulting in mechanical ileus.
      CONCLUSIONS: The possible non-fragmentation and migration of the V-BAR confirms
      the need to follow up patients with plain abdominal radiography performed at
      short intervals during the postoperative period.

PMID- 15973225
TI  - Multidetector CT of the small bowel: evaluation after oral hyperhydration with
      isotonic solution.
AB  - PURPOSE: The aim of our study was to assess the diagnostic capabilities of
      multidetector CT in the evaluation of the small bowel in different pathological
      conditions, with the use of oral hyperhydration with isotonic solution. MATERIALS
      AND METHODS: The study retrospectively evaluated 106 patients who underwent
      multidetector CT of the small bowel. Four groups were considered on the basis of
      the clinical findings: group A (48 cases), with suspected or certain chronic
      inflammatory disease of the small bowel; group B (16 cases), with suspected
      neoplastic lesion of the small bowel; group C (17 cases), patients affected by
      malabsorption; group D (25 cases), others: 13 cases with non-specific abdominal
      pain, 4 cases with occult bleeding, 8 cases affected by fever of unknown origin.
      Thirteen patients had previously undergone surgical intestinal resection. In all
      cases the CT examination was performed after the oral administration of 2000 mL
      polyethylene glycol electrolyte balanced solution; before the scan, N-butyl
      scopolamine or glucagon were administered intravenously to obtain rapid
      inhibition of bowel peristalsis. All multidetector CT scans were acquired at
      baseline and 50 seconds after the I.V. administration of 110-130 ml high
      concentration non-ionic iodinated contrast medium. The images were subsequently
      processed on a dedicated workstation (Advantage Windows 4.0, GE Medical Systems)
      to obtain multiplanar reconstruction (MPR). We considered the following CT
      findings: fold distribution, wall thickening and stratification and contrast
      enhancement, extraparietal involvement and abnormalities of the abdominal organs.
      The CT diagnoses were compared with the clinical and laboratory findings (86
      cases) and with the results of barium follow-through (55 cases), ileo-colonoscopy
      (45 cases) or surgery (28 cases). RESULTS: CT examination allowed the correct
      diagnosis in 86/106 cases (89%); 20 patients were not included in the study
      because of a poor (11 cases) or absent (9 cases) small bowel loop distension. The
      final diagnoses in the 86 patients were: Crohn's disease of the small bowel (38
      cases), Crohn's disease of the duodenum (1 case), granulomatous colitis (3
      cases), malabsorption (8 cases), neoplastic lesion (4 cases), post-radiation
      conglomeration of ileal loops (1 case), intestinal lymphangiectasia (1 case),
      ulceration of the last ileal loop (1 case). In 29 cases no abnormalities of the
      small bowel were found. Spiral CT yielded 52 true positive cases, 5 false
      negative cases, 2 false positive cases, and 27 true negative RESULTS: The
      sensitivity of the technique was 91%, specificity 93% and diagnostic accuracy
      92%. CONCLUSIONS: Multidetector CT of the small bowel performed after oral
      hyperhydration with isosmotic solution, proved to be an accurate and thorough
      technique. It can be considered a safe and effective alternative to conventional
      radiographic studies and to small bowel spiral CT enema in patients that refuse
      the nasojejunal balloon catheter or the administration of methylcellulose.

PMID- 15973227
TI  - The Color Doppler with contrast agent US in the study of post Cholecistectomy
      Syndrome.
AB  - PURPOSE: The aim of this study was to evaluate the study of intra- and extra
      biliary ducts by contrast-enhanced colour-Doppler in patients who have undergone
      laparoscopic cholecystectomy. MATERIALS AND METHODS: Contrast-enhanced colour
      Doppler US was performed in 15 patients who had undegone laparoscopic
      cholecystectomy. The US contrast agent was introducted into the Kehr or Pedinelli
      tube to allow visualisation of the bile ducts and duodenum. RESULTS: The colour
      Doppler study enabled visualisation of the contrat agent in the intra- and extra
      hepatic bile ducts and in the duodenum in all patients, thereby permitting the
      accurate study of the post-operative course. The data obtained were confirmed by
      conventional radiology. CONCLUSIONS: The advantages of this US ultrasound
      technique are the complete absence of ionising radiation and no intolerance to
      the US contrast agent. This technique could therefore be used in selected
      patients as an alternative to trans-Kehr and trans-Pedinelli cholangyography.

PMID- 15973228
TI  - MR findings in lipoma arborescens of the knee: our experience.
AB  - PURPOSE: This paper describes the role of MR imaging in the identification of the
      different macroscopic patterns of lipoma arborescens. MATERIALS AND METHODS:
      Between June 1995 and January 2004, a total of 6387 MR examinations of the knee
      were retrospectively assessed for the presence of lipoma arborescens. The MR
      examinations were performed using a superconductive 0.5 T MR unit with a
      transmitting/ receiving coil dedicated for the extremities. The MR images were
      acquired with SE T1-weighted, GE T2-weighted and STIR sequences in sagittal,
      coronal and axial planes with 3-mm thickness and 1-mm gap. RESULTS: Lipoma
      arborescens was identified in 9 patients (mean age: 36 years). In 2/9 cases a
      localized lipoma arborescens was detected as a well-marginated single nodule on
      the suprapatellar bursa without irregularity or synovial hyperplasia. In the
      remaining 7 cases diffuse lipoma arborescens was identified on the wall of the
      suprapatellar bursa. In one case of diffuse lipoma arborescens there was
      involvement of both knees. In all cases the MR findings were verified at surgery
      and the final diagnosis was made by histological examination. CONCLUSIONS: MR
      imaging shows a high accuracy in the identification and characterization of
      lipoma arborescens, due to its multiplanar capabilities and high contrast
      resolution. MRI allows correct evaluation of size and grade, accurate treatment
      planning and effective follow-up, avoiding the need for synovial biopsy.

PMID- 15973229
TI  - Usefulness of gadolinium in MRI evaluation of non surgically treated herniated
      disk.
AB  - PURPOSE: The rationale for the use of Gadolinium (Gd) in the MRI evaluation of
      non surgically treated herniated disk is based on the known presence of
      inflammatory granulation tissue and neoangiogenesis which plays an important role
      in both pain and the spontaneous resorption of the hernia. THE AIM: of this study
      was to determine the usefulness of Gd in MRI examination for detecting the
      inflammatory reaction around the discal hernia. MATERIALS AND METHODS: Thirty
      eight patients (mean age 45 years; range 20-70 years) with non surgically treated
      herniated disk were evaluated with MRI between January 2000 and July 2004. T2w
      FAST-SE sagittal and T1w-SE transaxial and sagittal images were acquired before
      and after the administration of Gd. RESULTS: Twenty out of 22 patients with acute
      sciatic pain (symptoms =/< 40 days) showed significant peri-hernial enhancement
      which facilitated the differential diagnosis with other extradural lesions, such
      as synovial cysts (2/22 cases), as well as the correct definition of the
      extension of discal hernia in the spinal canal. In the remaining 16 with chronic
      sciatic pain (symptoms > 6 months) the discal hernia did not show peri-hernial
      enhancement. CONCLUSIONS: In MRI evaluation of the herniated disk, peri-hernial
      enhancement is correlated with inflammatory reaction around the hernia which is
      associated with acute symptoms. The absence of peri-hernial enhancement in
      chronic herniated disk is due to the poorly vascular fibrotic tissue. Therefore,
      peri-hernial enhancement facilitates the differential diagnosis in uncertain
      cases and represents a reliable prognostic index of response to non-surgical
      therapy and of the possible spontaneous resorption of discal hernia.

PMID- 15973230
TI  - Radiofrequency thermal ablation of non spinal osteoid osteoma: remarks on method.
AB  - Osteoid osteoma is a small benign tumor, with a ''nidus'' that rarely exceeds 15
      mm in diameter. It is relatively common in males, especially teenagers and young
      adults. It involves mainly the appendicular skeleton, the femur in particular,
      and rarely the axial skeleton. It requires treatment because it causes intense
      pain. In recent years alternative, less invasive, treatments have been proposed,
      such as drilling combined with ethanol injections, and thermal ablation with
      laser or radiofrequency. This study assesses 117 patients affected by osteoid
      osteoma, treated by radiofrequency thermal ablation between June 2001 and
      November 2003. We describe the patient recruitment procedure, CT-guided
      technique, the percutaneous approach, thermal ablation, and the instruments used.
      Data were analyzed thoroughly, and modifications that have improved the effects
      of treatment have been highlighted. The results achieved since the method was
      perfected have been extremely encouraging, confirming that the technique is very
      effective if performed correctly. For that reason radiofrequency thermal ablation
      has become the treatment of choice for non-spinal osteoid osteoma at Rizzoli
      Orthopaedic Institute.

PMID- 15973231
TI  - Turbo-Proton Echo Planar Spectroscopic Imaging (t-PEPSI) MR technique in the
      detection of diffuse axonal damage in brain injury. Comparison with Gradient
      Recalled Echo (GRE) sequence.
AB  - PURPOSE: Diffuse axonal injury (DAI) is a common type of primary neuronal injury
      in patients with severe traumatic brain injury, and is frequently accompanied by
      tissue tear haemorrhage. The T2*-weighted gradient-recalled echo (GRE) sequences
      are more sensitive than T2-weighted spin-echo images for detection of
      haemorrhage. This study was undertaken to determine whether turbo-PEPSI, an
      extremely fast multi-echo-planar-imaging sequence, can be used as an alternative
      to the GRE sequence for detection of DAI. MATERIALS AND METHODS: Nineteen
      patients (mean age 24,5 year) with severe traumatic brain injury (TBI), occurred
      at least 3 months earlier, underwent a brain MRI study on a 1.5-Tesla scanner. A
      qualitative evaluation of the turbo-PEPSI sequences was performed by identifying
      the optimal echo time and in-plane resolution. The number and size of DAI
      lesions, as well as the signal intensity contrast ratio (SI CR), were computed
      for each set of GRE and turbo-PEPSI images, and divided according to their
      anatomic location into lobar and/or deep brain. RESULTS: There was no significant
      difference between GRE and turbo-PEPSI sequences in the total number of DAI
      lesions detected (283 vs 225 lesions, respectively). The GRE sequence identified
      a greater number of hypointense lesions in the temporal lobe compared to the t
      PEPSI sequence (72 vs 35, p<0.003), while no significant differences were found
      for the other brain regions. The SI CR was significantly better (i.e. lower) for
      the turbo-PEPSI than for the GRE sequence (p<0.00001). CONCLUSIONS: Owing to its
      very short scan time and high sensitivity to the haemorrhage foci, the turbo
      PEPSI sequence can be used as an alternative to the GRE to assess brain DAI in
      severe TBI patients, especially if uncooperative and medically unstable.

PMID- 15973232
TI  - Osteodistraction in the craniofacial region.
AB  - In the specific field of maxillofacial surgery, the use of osseous distraction is
      always more and more helpful not only in the rehabilitation of malformation
      pathologies, but also in the clinical situations that require bone deficit
      correction resulting from traumatic events and postsurgical effects, for example
      oncologic surgery. The reason for this versatility in the distraction protocols
      is, undoubtedly, due to the fact that, at present, they are valid surgical
      methods in alternative to or supporting maxillofacial surgery, since they are
      feasible from a very early age and they obtain a level of distraction that is
      often higher than with orthopedic devices or conventional surgery. There are
      multiple indications for osteodistraction and they range from cases of hyper- or
      hypodevelopment of the maxilla and mandible, of both their anteroposterior and
      transverse components, to complex syndromes such as cleft lip and palate. Even
      the clinical distraction of the upper and middle thirds of the cranium, through a
      coronal craniotomy, has been shown to be a safe surgical procedure and it allows,
      for example, the successful rehabilitation of adult patients suffering from
      hemifacial microsomia or craniosynostosis. With the continuous and constant
      evolution of the integration of osteodistraction principles in the rehabilitation
      of the craniofacial region, an ever-more effective interdisciplinary relationship
      between orthodontics and osteodistraction has been seen with growing interest.
      More often treatment plans are programmed in which the orthodontic and
      osteodistractive phases are integrated and complete each other, each supporting
      the other. Scientific and clinical progress achieved in this field in recent
      years, allows more and more refined therapeutic solutions to be programmed,
      permitting craniofacial operations and to repair an ankylotic dental arch or
      reposition osteointegrated implants to the most convenient bone sites.

PMID- 15973233
TI  - Resorbable plates in maxillary fixation. A 5-year experience.
AB  - AIM: Metallic plates and screws have become the routine way of stabilizing the
      facial skeleton; however, there are many disadvantages in the use of metallic
      devices. Fixation systems made of biocompatible absorbable material, with
      appropriate load-bearing properties and sufficient degradation rate can overcome
      these disadvantages. Recently, resorbable materials were tested in maxillary,
      mandibular and chin osteotomies. Despite a lot of reports on the use of
      resorbable bone fixation devices in cranio-maxillo-facial application are now
      available, their use in preprosthetic surgery has yet to be adequately
      documented. The Authors report their 5-year experience in the employment of
      resorbable fixation in surgery of the superior maxilla, involving orthognathic
      and preprosthetic procedures of the upper jaws. The surgical technique is
      described and usefulness and advantages are discussed. METHODS: Plates and screws
      were composed of an 82% poly-L-lactic acid/18% polyglycolic acid copolymer (PLLA
      PGA); 50 orthognathic and 5 preprosthetic procedures of upper jaws were involved,
      performing Le Fort I osteotomies in all cases. RESULTS: Our operations were were
      carried out without complications. Follow-up ranged from 6 months to 5 years. One
      patient developed a localized buccal space infection which resolved after a
      course of antibiotics given orally. CONCLUSIONS: Resorbable fixation should be
      considered adequate for fixation in maxillary surgery.

PMID- 15973234
TI  - SEM analysis of zirconium brackets using MIM technology.
AB  - AIM: The need to be able to use a material with esthetic characteristics of
      ceramic and mechanical properties of the metallic brackets has led clinical and
      industrial research towards the realization of zirconium brackets. These brackets
      seem to respond to both the requirements of new esthetic concepts and of
      interesting biomechanical qualities: hardness, resistance to abrasion, resistance
      to compression, reduced coefficient of friction during mechanical sliding,
      stability in a humid temperature and to the aggression of oral fluids. METHODS:
      Twenty samples of zirconium brackets have been observed at SEM realized using the
      metal injection molding (MIM) technology: 10 new ones used as base samples and 10
      used samples with the purpose of assessing the morphologic aspect and the
      structural variations after clinical use. RESULTS: The comparison the samples
      showed some structural changes regarding the surface of the body of the brackets,
      while slot and wings maintain an interesting stability of construction, a
      moderate degree of abrasion even after the application of considerable clinical
      strength. CONCLUSIONS: The conclusion is drawn that the positive clinical
      response in the use of these brackets and the limited scientific literature on
      the use of zirconium in orthodontics is worthy of further research.

PMID- 15973235
TI  - Qualitative comparison of MR TSE T2 and HASTE in temporomandibular disorders.
      Clinical observations.
AB  - AIM: The aim of the study is to evaluate the quality of the temporal mandibular
      joint (TMJ) imaging in patients with lack of condyle-disk coordination with the
      Half-Fourier Acquisition Single Shot Turbo Spin Echo (HASTE), and compare it with
      the quality of TSE T2-weighted images. METHODS: Twenty-seven patients were
      selected (12 men and 15 women; age range 17-69 years) with medical history
      negative for facial trauma or surgery. The instrument used was a Siemens 1.5
      Tesla with bilateral coil dedicated for studying both TMJs. TSE T2-weighted and
      HASTE images in the parasagittal axis with open and closed mouth were obtained
      for both joints. RESULTS: The quality of the TSE T2-weighted images was better
      for all parameters considered (both at open and at closed mouth) than the HASTE
      images; however, the latter method is considerably quicker. CONCLUSIONS: HASTE
      was found to be a valid method for use as rapid screening to study the TMJ and
      for use in patients who are unable to maintain an immobile position. Time and
      cost required for the examination are drastically reduced.

PMID- 15973236
TI  - Bone biological plate for stabilization of maxillary inferior repositioning.
AB  - AIM: Inferior repositioning of the maxilla to correct vertical maxillary
      deficiency has been one of the more unstable orthognathic procedures performed.
      Different surgical techniques have been proposed to stabilize downward movement
      of the maxilla. The aim of this study was to evaluate the skeletal stability of
      maxillary anterior downgrafting using bone biological plates in association to
      bone plates and bone graft for skeletal stabilization. METHODS: The records of 6
      patients were evaluated cephalometrically, analyzing the presurgical, immediate
      postsurgical and long-term follow-up radiographs. All patients had one-piece Le
      Fort I osteotomy with anterior downgraft of at least 2 mm at point A. Any
      horizontal movement of the maxilla concomitant with the downgraft was no more
      than 5 mm. Rigid fixation with titanium miniplates and screws and with bone
      biological plate was used to stabilize the maxilla. In the sample of 6 patients,
      3 underwent one-jaw (maxilla only) surgery and 3 two-jaw surgery. RESULTS: The
      mean surgical inferior downgrafting at point A was 5+/-1.4 mm (P<0.001) with a
      relapse of 0.16+/-1. 63 mm (3.2% of surgical movement). The mean surgical
      inferior downgrafting at the anterior nasal spine (ANS) was 5.66+/-1.36 mm
      (P<0.001) with a relapse of 0.41+/-1.56 mm (7.32% of surgical movement). Relapse
      in the vertical dimension failed to reach any statistical significance for all
      maxillary landmarks. CONCLUSIONS: Anterior downgrafting of the maxilla with this
      fixation method seems to be a stable and predictable procedure. The use of bone
      biological plates seems to substantially improve skeletal stability even if
      further investigations with a more consistent sample of patients is required.

PMID- 15973237
TI  - Allergy and desensitization to latex. Clinical study on 50 dentistry subjects.
AB  - AIM: Nowadays latex allergy represents a relevant social and occupational problem
      because this substance constitutes the first material to realise many dental and
      non dental products; then, there is a cross-reactivity between latex allergens
      and proteins present in many vegetal foods. The aim of our research was to find
      latex allergy cases experimenting a percutaneous desensitization protocol.
      METHODS: Among 50 examined subjects, those patients resulting positive to thiuram
      mix by patch test have been submitted to desensitization after removal of all
      latex products and substances giving cross-allergy (kiwi, celery, chestnuts,
      tomato, banana etc.). Desensitization has been carried out by using latex glove
      from 10 s progressively to 1 h after 1-year treatment. RESULTS: In 7 patients out
      of 11 (63.6%) regression of symptoms has been verified; 2 patients (18.2%) have
      declined treatment and 2 patients (18.2%) have showed no regression. CONCLUSIONS:
      Apart immunotherapy and DNA-vaccines, nowadays percutaneous desensitization is
      the most efficacious, safe and easy treatment for latex allergic patients; it has
      no collateral effects during its execution and no symptoms coming back to work,
      but it needs further verifications.

PMID- 15973238
TI  - Patient at high hemorrhagic risk. Surgical management of three cases and review
      of the literature.
AB  - The surgical treatment of 3 cases of dental patients at high hemorrhagic risk is
      described: a man with Von Willebrand disease and 2 women, 1 with platelet
      deficiency with cirrhosis of the liver and the other with autoimmune idiopathic
      thrombocytopenic purpura. The patients were hospitalized in order to monitor
      these cases in cooperation with the University Hematology Center.

PMID- 15973239
TI  - HIV prevalence, unrecognized infection, and HIV testing among men who have sex
      with men--five U.S. cities, June 2004-April 2005.
AB  - Well into the third decade of the human immunodeficiency virus (HIV) epidemic,
      rates of HIV infection remain high, especially among minority populations. Of
      newly diagnosed HIV infections in the United States during 2003, CDC estimated
      that approximately 63% were among men who were infected through sexual contact
      with other men, 50% were among blacks, 32% were among whites, and 16% were among
      Hispanics. Studies of HIV infection among young men who have sex with men (MSM)
      in the mid to late 1990s revealed high rates of HIV prevalence, incidence, and
      unrecognized infection, particularly among young black MSM. To reassess those
      findings and previous HIV testing behaviors among MSM, CDC analyzed data from
      five of 17 cities participating in the National HIV Behavioral Surveillance
      (NHBS) system. This report summarizes preliminary findings from the HIV-testing
      component of NHBS, which indicated that, of MSM surveyed, 25% were infected with
      HIV, and 48% of those infected were unaware of their infection. To decrease HIV
      transmission, MSM should be encouraged to receive an HIV test at least annually,
      and prevention programs should improve means of reaching persons unaware of their
      HIV status, especially those in populations disproportionately at risk.

PMID- 15973240
TI  - Use of social networks to identify persons with undiagnosed HIV infection--seven
      U.S. cities, October 2003-September 2004.
AB  - An estimated 250,000 persons living with human immunodeficiency virus (HIV) in
      the United States are not aware of their infections and their risk for
      transmitting HIV. As part of CDC's Advancing HIV Prevention Initiative,
      identifying persons with undiagnosed HIV infection and linking them to medical
      care and prevention services is a national priority. In 2003, a 2-year
      demonstration project was begun with nine community-based organizations (CBOs) in
      seven cities to evaluate the effectiveness of using a social network strategy at
      multiple sites to identify persons at risk for HIV infection and direct them to
      HIV counseling, testing, and referral (CTR). In this strategy, HIV-positive
      persons and HIV-negative persons at high risk (i.e., recruiters) are enlisted to
      recruit for CTR persons from their social, sexual, and drug-use networks (i.e.,
      network associates [NAs]) believed to be at risk for HIV infection. This report
      summarizes preliminary results from the first year of this 2-year project, which
      indicated that 133 persons recruited 814 NAs, resulting in 46 newly identified
      HIV infections (approximately 6% of all persons tested). Health departments and
      CBOs should consider this strategy as an effective method for recruiting persons
      for CTR and identifying those with undiagnosed HIV infection.

PMID- 15973241
TI  - Human tuberculosis caused by Mycobacterium bovis--New York City, 2001-2004.
AB  - In March 2004, a U.S.-born boy aged 15 months in New York City (NYC) died of
      peritoneal tuberculosis (TB) caused by Mycobacterium bovis infection. M. bovis, a
      bacterial species of the M. tuberculosis complex, is a pathogen that primarily
      infects cattle. However, humans also can become infected, most commonly through
      consumption of unpasteurized milk products from infected cows. In industrialized
      nations, human TB caused by M. bovis is rare because of milk pasteurization and
      culling of infected cattle herds. This report summarizes an ongoing, multiagency
      investigation that has identified 35 cases of human M. bovis infection in NYC.
      Preliminary findings indicate that fresh cheese (e.g., queso fresco) brought to
      NYC from Mexico was a likely source of infection. No evidence of human-to-human
      transmission has been found. Products from unpasteurized cow's milk have been
      associated with certain infectious diseases and carry the risk of transmitting M.
      bovis if imported from countries where the bacterium is common in cattle. All
      persons should avoid consuming products from unpasteurized cow's milk.

PMID- 15973249
TI  - Aortic dissection--an update.
AB  - Acute aortic dissection is a medical emergency with high morbidity and mortality
      requiring emergent diagnosis and therapy. Rapid advances in noninvasive imaging
      technology have facilitated the early diagnosis of this condition and should be
      considered in the differential diagnosis of any patient with chest, back, or
      abdominal pain. Emergent surgery is the treatment for patients with type A
      dissection while optimal medical therapy is appropriate in patients with
      uncomplicated type B dissection. Adequate beta-blockade is the cornerstone of
      medical therapy. Patients who survive acute aortic dissection need long-term
      medical therapy with beta-blockers and statins and appropriate serial imaging
      follow-up. Future advances in this field include biomarkers in the early
      diagnosis of acute aortic dissection and presymptomatic diagnosis with genetic
      screening. Overall patients with aortic dissection are at high risk for an
      adverse outcome and need to be managed aggressively in hospital and long term
      with frequent follow-up.

PMID- 15973254
TI  - Observations from a maternal and infant hospital in Kabul, Afghanistan--2003.
AB  - Afghanistan is believed to have one of the highest infant and maternal mortality
      rates in the world. As a result of decades of war and civil unrest, Afghan women
      and children suffer from poor access to health services, harsh living conditions,
      and insufficient food and micronutrient security. To address the
      disproportionately high infant and maternal mortality rates in Afghanistan, the
      US Department of Health and Human Services pledged support to establish a
      maternal health facility and training center. Rabia Balkhi Hospital in Kabul,
      Afghanistan, was selected because this hospital admits approximately 36,000
      patients and delivers more than 14,000 babies annually. This article reports the
      initial observations at Rabia Balkhi Hospital and describes factors that
      influenced women's access, the quality of care, and the evaluation health care
      services. This observational investigation examined areas of obstetric,
      laboratory and pharmacy, and ancillary services. The investigators concluded that
      profound changes were needed in the hospital's health care delivery system to
      make the hospital a safe and effective health care facility for Afghan women and
      children and an appropriate facility in which to establish an Afghan provider
      training program for updating obstetric skills and knowledge.

PMID- 15973255
TI  - A randomized controlled trial of the effects of applied relaxation training on
      reducing anxiety and perceived stress in pregnant women.
AB  - The purpose of this study was to investigate the effect of applied relaxation
      training on reducing anxiety and perceived stress among pregnant women. A
      randomized controlled trial with a prospective pretest-posttest experimental
      design was used. One hundred ten primigravid women (mean age = 23.8 years) in
      their second trimester (mean of gestational age = 17.8 weeks) were randomly
      assigned into experimental and control groups. The experimental group received
      routine prenatal care with applied relaxation training, and the control group
      received only routine prenatal care. State/trait anxiety was measured with the
      Spielberger State-Trait Anxiety Inventory, and perceived stress was measured with
      the Cohen Perceived Stress Scale. There were significant reductions in
      state/trait anxiety and perceived stress for the experimental group compared with
      the control group after the intervention. The findings suggest beneficial effects
      of relaxation on reducing anxiety and perceived stress in pregnant women.
      Teaching relaxation techniques could serve as a resource for improving maternal
      psychological health.

PMID- 15973256
TI  - Living the reality of forced sex work: perspectives from young migrant women sex
      workers in northern Vietnam.
AB  - Young women are often lured or forced into selling sex as a result of migrating
      from rural to urban areas to find work. In this setting, they are exposed to high
      risk situations, which may leave them vulnerable to exploitation. Using
      interviews with young migrant women currently working as sex workers in northern
      Vietnam, we recorded the perspectives of their initiation into sex work and life
      as a sex worker. The study found that high levels of forced sex and sexual
      exploitation were experienced by the majority of the young women interviewed. The
      young women describe their entry into sex work, first sexual experience
      (intercourse), violence, and condom negotiation and use. Although access to
      health care was available, the young women perceived the stigma attached to sex
      work as a barrier to receiving health care, and thus, preferred health education
      and care from peers. Health education programs focusing on peer education and
      support are essential for protecting and empowering these young women. In
      addition, policies and programs must work toward effective strategies to protect
      young migrant women.

PMID- 15973257
TI  - Midwifery curriculum for auxiliary maternity nurses: a case study in the
      Dominican Republic.
AB  - Although most deliveries in the Dominican Republic occur within hospitals,
      maternal mortality in that nation remains high. In nonteaching hospitals, almost
      all of the vaginal births are attended by maternity auxiliary nurses. This
      article reports on a series of educational conferences for maternity auxiliary
      nurses in 1 hospital that were developed in response to the maternal mortality
      rate there. These conferences, taught by a team of midwives from the continental
      United States and Puerto Rico, used a midwifery curriculum with a participatory
      action methodology. The educational initiative has developed into a
      nongovernmental organization named Proyecto ADAMES to build capacity among
      auxiliary nurses. A qualitative evaluation of the effectiveness of Proyecto
      ADAMES in improving the knowledge, skills, and attitudes of the auxiliary nurses
      revealed positive behavioral changes despite weak documentation of their newly
      acquired knowledge and skills. Findings suggest that midwifery education for
      auxiliary maternity nurses in the Dominican Republic may contribute to maternal
      mortality reduction.

PMID- 15973259
TI  - Caring for global caregivers: a call to action.

PMID- 15973261
TI  - Improving the health of women in developing countries: the time is now.
AB  - The health problems of women in developing countries remain far too low on the
      international community's list of priorities. Progress can be made toward
      decreasing maternal mortality in resource-poor countries without sizable new
      research efforts. Strategies include improving access to emergency obstetric care
      and family-planning services. Reducing maternal mortality rates by 75% is one of
      the key Millenium Development Goals. Making women's health a priority will
      improve the outlook for women in the developing world.

PMID- 15973262
TI  - Mothers, midwives, and HIV/AIDS in Sub-Saharan Africa.
AB  - This article reviews clinical and program issues in the prevention of mother to
      child transmission (PMTCT) of HIV in sub-Saharan Africa. Topics include
      prevention of infection, voluntary counseling and testing, prenatal care, labor
      and birth, postpartum, family planning, infant feeding, and the role of
      traditional birth attendants. Programs providing short-course antiretroviral
      therapy to prevent infant infection are contrasted with comprehensive programs
      offering antiretroviral therapy and medical care to mothers, children, and
      families. Feminization of the epidemic is related to gender inequalities that
      facilitate the spread of HIV and make pregnant women an especially vulnerable
      group. Nurses and midwives are the primary health care providers for most of the
      population in sub-Saharan Africa. They are the backbone of the new PMTCT programs
      and will be the largest group of health workers available to diagnose and treat
      opportunistic infections and dispense antiretroviral therapy. But they have
      received little training and support to provide AIDS care and treatment and are
      rarely consulted when plans are made about workforce issues and capacity
      development in the health sector. Clinical training, leadership skills, salary
      support, expansion of the nursing workforce, and development of expanded roles
      for nurses and midwives in AIDS care are needed to help them turn the tide of the
      epidemic.

PMID- 15973263
TI  - A midwife's day in Namibia and South Africa.

PMID- 15973264
TI  - Obstetric fistula: a preventable tragedy.
AB  - Obstetric fistula disables millions of women and girls in developing countries,
      primarily in sub-Saharan Africa and South Asia. The United Nations Population
      Fund (UNFPA) recently launched a global campaign to end fistula, labeling this
      condition a preventable and treatable tragedy. Obstetric fistula overwhelmingly
      results from obstructed labor, which occurs in cases of cephalopelvic
      disproportion and malpresentation. Cephalopelvic disproportion often complicates
      deliveries in young, primiparous women of low gynecologic age. Social factors,
      including young age at marriage and malnutrition of girl children, can also
      contribute to cephalopelvic disproportion. These social etiologies must be
      addressed by prevention campaigns. Direct prevention of fistula can occur during
      delivery when skilled providers identify women and girls at risk for obstetric
      fistula and link them with innovative interventions, such as Fistula Prevention
      Centers, through which they can more readily access emergency obstetric care, and
      by setting strict time limits for laboring at home without progress. Community
      based programs, such as the Tostan program in West Africa, use social education
      to prevent fistula. Moreover, effective surgical techniques for fistula repair
      are available in some settings and should be expanded to reach those in need.
      Midwives can play a key role in the prevention and treatment of this tragic
      obstetric complication.

PMID- 15973266
TI  - Implementing a facility-based maternal and perinatal health care surveillance
      system in Afghanistan.
AB  - Afghanistan has one of the highest maternal and perinatal mortality rates in the
      world. Lack of a health information system presented obstacles to efforts to
      improve the quality of care and reduce mortality. To rapidly overcome this
      deficit in a large women's hospital, staff implemented a facility-based maternal
      and perinatal surveillance system known as "BABIES," which is specially designed
      for intervention and evaluation in low-resource settings. During a 12-month
      period, 15,509 deliveries resulted in 28 maternal deaths and a perinatal
      mortality rate of 56 per 1000 births. When stratified by birth weight and
      perinatal period of death, fetuses weighing at least 2500 g who died during the
      antepartum period contributed the most cases of perinatal death. This finding
      suggests that the greatest reduction in perinatal mortality would be realized by
      increasing access to high-quality antepartum care. Among fetuses weighing at
      least 2500 g, 93 deaths occurred during the intrapartum period. These deaths will
      continue to be monitored to ensure that the chosen interventions are improving
      intrapartum care for mothers and newborns. Because of its simplicity,
      flexibility, and ability to identify interventions, BABIES is a valuable tool
      that enables clinicians and program managers to prioritize resources.

PMID- 15973267
TI  - Recognition of and response to postpartum hemorrhage in rural northern India.
AB  - This study describes the results of a Morbidity and Performance Assessment (MAP)
      conducted to provide insight into the medical factors contributing to maternal
      and newborn morbidity and mortality in a rural district of northern India, and to
      use these insights to develop a locally appropriate, community-based safe
      motherhood program The MAP study was based on verbal autopsy method. Five hundred
      ninety-nine women (or in the case of 9 maternal deaths, a family member)
      participated in the study. This article describes a subsample of women who
      reported signs or symptoms suggesting excessive bleeding (n = 159). Findings
      include a poor knowledge of danger signs; poor problem recognition during labor,
      birth, and the immediate postpartum period; and a low level of health seeking
      that was consistent with poor recognition. Maternal sociodemographic
      characteristics, antenatal care use, and knowledge of danger signs were generally
      not associated with problem recognition and health seeking. The case fatality
      rate was 4%. These findings suggest an urgent need to understand the phenomenon
      of problem recognition and to integrate this into the design of interventions to
      reduce delays in health seeking.

PMID- 15973268
TI  - Residential environmental risks for reproductive age women in developing
      countries.
AB  - Published research suggests there is an association between maternal inhalation
      of common ambient air pollutants and adverse birth outcomes, including an
      increased risk for preterm delivery, intrauterine growth retardation, small head
      circumference, low birth weight, and increased rate of malformations. The air
      pollutants produced by indoor combustion of biomass fuels, used by 50% of
      households worldwide, have been linked to acute lower respiratory infections, the
      single most important cause of mortality in children under the age of 5. This
      report describes a hypothesis-generating study in West Wollega, Ethiopia,
      conducted to assess airborne particulate matter concentrations in homes that
      combust biomass fuels (biomass homes). Respirable suspended particulate matter
      was measured in biomass homes and nonbiomass homes using NIOSH method 0600.
      Measured airborne particulate concentrations in biomass homes were up to 130
      times higher than air quality standards. These findings, in part, confirm that
      exposure to indoor air pollutants are a major source of concern for mother/child
      health. Midwives are encouraged to raise awareness, contribute to research
      efforts, and assist in interventions.

PMID- 15973269
TI  - Effectiveness of lifesaving skills training and improving institutional emergency
      obstetric care readiness in Lam Dong, Vietnam.
AB  - Essential obstetric care is promoted as the prime strategy to save women's lives
      in developing countries. We measured the effect of improving lifesaving skills
      (LSS) capacity in Vietnam, a country in which most women deliver in health
      facilities. A quasi-experimental study was implemented to assess the impact of
      LSS training and readiness (availability of essential obstetric equipment,
      supplies, and medication) on the diagnosis of life-threatening obstetric
      conditions and appropriate management of labor and birth. The intervention (LSS
      training and readiness) was provided to all clinics and hospitals from 1 of 3
      demographically similar districts in southcentral Vietnam, to hospitals only in
      another district, with the third district serving as the comparison group.
      Detection of life-threatening obstetric conditions increased in both experimental
      clinics and hospitals, but the intervention only improved the management of these
      conditions in hospitals. Management of life-threatening obstetric conditions is
      most effective in hospitals. The intervention did not clearly benefit women
      delivering in clinics.

PMID- 15973270
TI  - Cultural barriers to exclusive breastfeeding by mothers in a rural area of
      Cameroon, Africa.
AB  - Because of the known nutritional and health benefits to the infant, the World
      Health Organization recommends that women in resource-poor countries exclusively
      breastfeed until their babies reach 6 months of age. In the primarily rural
      geographical region of the North West Province of Cameroon, previous studies
      identified the prevalence of breastfeeding to be 90%. It is common knowledge that
      women are culturally encouraged to mix-feed their infants, but the extent of
      these feeding practices is not known. The objective of this study was to identify
      the extent of mixed feeding/supplementation and the cultural/social barriers to
      exclusive breastfeeding. All women surveyed introduced water and food
      supplementation prior to 6 months of age, with more than 38% giving water in the
      first month of life. Mothers identified cultural factors influencing their
      decision to mix-feed their babies, which included 1) pressures by village elders
      and families to supplement because it is a traditional practice, 2) belief that
      breast milk is an incomplete food that does not increase the infants weight, 3)
      belief that all family members should receive the benefit of food grown in the
      family farm, and 4) the taboo of prohibiting sexual contact during breastfeeding.

PMID- 15973271
TI  - Barriers to and facilitators for newborn resuscitation in Malawi, Africa.
AB  - Newborn resuscitation is a key component of efforts to reduce neonatal morbidity
      and mortality. This article reports the findings of focus groups conducted to
      explore the barriers and facilitators present for obstetric nurse providers in a
      central urban hospital in Malawi regarding the training and provision of neonatal
      resuscitation. All obstetric nurse providers in this setting participated in
      focus groups; these groups identified 4 themes: 1) confidence in their skills in
      assessing newborns and recognizing the need for resuscitation, 2) a lack of
      resources, 3) facilitators who would enable them to introduce resuscitation, and
      4) solutions to the current problems. Resource shortages and barriers to
      providing care included availability of staff, equipment, and supplies; labor
      ward geography; ethical dilemmas; and the lack of standard protocols regarding
      newborn resuscitation. Facilitators were professional experience and the critical
      load of deliveries performed. Solutions to barriers included small resource
      additions as well as long-term policy changes. With standard policy and
      protocols, experienced, confident nurses could overcome the barriers to providing
      newborn resuscitation. This group identified ways to change systems to decrease
      infant mortality, thereby improving the health and quality of life of women
      receiving care in Malawi.

PMID- 15973272
TI  - Cryotherapy treatment for cervical intraepithelial neoplasia: women's experiences
      in Peru.
AB  - Our objective was to examine cryotherapy experiences among women who received
      treatment for cervical intraepithelial neoplasia in a cervical cancer prevention
      project in rural Peru. The sample consisted of all women receiving cryotherapy
      during a 4-month period (July through October 2001). Structured interviews were
      conducted to collect information about the adequacy of information provision,
      women's satisfaction with cryotherapy, their ability to comply with
      postcryotherapy recommendations and condom use, their experience with cryotherapy
      side effects, and their satisfaction with cryotherapy follow-up. Of the 224 women
      who were interviewed, user satisfaction with cryotherapy treatment was generally
      good. A few women engaged in sex earlier than 30 days after treatment, primarily
      due to partner pressure to resume sex and the women's inability to successfully
      negotiate abstention from sex. These couples were not always able to use condoms.
      The percentage of women reporting vaginal discharge was within the range of
      responses reported in other studies. Cryotherapy appears to be acceptable to
      women in low-resource settings such as Peru.

PMID- 15973273
TI  - Abortion and postabortion care: ethical, legal, and policy issues in developing
      countries.
AB  - This case study of a woman who wants to terminate her pregnancy but does not have
      access to safe services explores the technical, ethical, and legal effects of the
      Mexico City Policy (Global Gag Rule) on health care providers working in
      developing countries. This woman's self-induced termination resulted in an
      incomplete abortion, and she sought care from a midwife. The current Mexico City
      Policy effectively limits a health care provider's ability to offer abortion
      services and counseling, even when these services are legal. The policy has an
      adverse impact on women's access to safe care. The provision of comprehensive
      postabortion care, not restricted by the Mexico City Policy, is the key to
      preventing abortion-related morbidity and mortality.

PMID- 15973274
TI  - Latent tuberculosis infection and BCG vaccination.
AB  - One third of the world's population is infected with Mycobacterium tuberculosis ,
      and 5% to 10% of those infected will develop active disease. Identification and
      treatment of latent tuberculosis infection (LTBI) is an essential part of the
      public health strategy to control the spread of TB. The prenatal period provides
      an opportunity for obstetric providers to assist in this effort by offering
      testing and treatment to women at risk.

PMID- 15973281
TI  - Current resources for evidence-based practice, July/August 2005.

PMID- 15973282
TI  - Hepatitis C.

PMID- 15973291
TI  - Molecular mechanisms of myocardial infarction.
AB  - Despite an increased knowledge of risk factors for atherosclerotic heart disease,
      it remains nearly endemic in Western society. Despite the high penetrance, only a
      fraction of those with the disease progress to develop a frank myocardial
      infarction (MI). Over the past decade, it has become clear that inflammation
      plays an important role in the pathogenesis of MI. Inflammatory arterial disease
      therefore may be a better term for the subset of patients that develop the
      serious adverse consequences related to the rupture of the intracoronary plaque.
      Using newer molecular techniques such as high-throughput SNP analysis, genome
      wide scanning, and enriched pedigree analysis, many of the specific mechanisms
      underlying the inflammatory milieu involved in this transition have been
      elucidated and may help identify those at risk for the adverse events associated
      with atherosclerotic disease.

PMID- 15973302
TI  - Influence of public funding on health care for children.

PMID- 15973303
TI  - Physical activity recommendations: where do we go from here?

PMID- 15973304
TI  - Statistical process control and calcineurin inhibitor management.

PMID- 15973305
TI  - Screening for abnormalities of carbohydrate metabolism in teens.

PMID- 15973306
TI  - The changing approach to multicystic dysplastic kidney in children.

PMID- 15973307
TI  - Quantitative bone analysis in children: current methods and recommendations.

PMID- 15973308
TI  - Evidence based physical activity for school-age youth.
AB  - OBJECTIVES: To review the effects of physical activity on health and behavior
      outcomes and develop evidence-based recommendations for physical activity in
      youth. STUDY DESIGN: A systematic literature review identified 850 articles;
      additional papers were identified by the expert panelists. Articles in the
      identified outcome areas were reviewed, evaluated and summarized by an expert
      panelist. The strength of the evidence, conclusions, key issues, and gaps in the
      evidence were abstracted in a standardized format and presented and discussed by
      panelists and organizational representatives. RESULTS: Most intervention studies
      used supervised programs of moderate to vigorous physical activity of 30 to 45
      minutes duration 3 to 5 days per week. The panel believed that a greater amount
      of physical activity would be necessary to achieve similar beneficial effects on
      health and behavioral outcomes in ordinary daily circumstances (typically
      intermittent and unsupervised activity). CONCLUSION: School-age youth should
      participate daily in 60 minutes or more of moderate to vigorous physical activity
      that is developmentally appropriate, enjoyable, and involves a variety of
      activities.

PMID- 15973309
TI  - Prevalence of overweight in children with developmental disorders in the
      continuous national health and nutrition examination survey (NHANES) 1999-2002.
AB  - OBJECTIVE: To estimate the prevalence of overweight in children identified with
      developmental disorders on the basis of nationally representative survey data.
      STUDY DESIGN: We estimated the prevalence of overweight in children with
      developmental disorders on the basis of a recent large nationally representative
      survey. The continuous National Health and Nutrition Examination Survey (NHANES)
      1999-2002 included 4 questions to identify children with developmental disorders.
      Height and weight were used to calculate body mass index (BMI). BMI percentiles
      were estimated relative to the age- and sex-specific Centers for Disease Control
      and Prevention growth reference. The 85th percentile BMI defined at-risk-for
      overweight and the 95th percentile BMI defined overweight. RESULTS: We found a
      higher prevalence of at-risk-for overweight and overweight among children with
      limitations in physical activity and a higher prevalence of overweight in girls
      with learning disabilities, compared with children without these conditions,
      after adjustment for age and race-ethnicity. CONCLUSION: To the extent that
      children with developmental disorders are included in large representative
      surveys, the data suggest that children with developmental disorders have a risk
      for overweight that is at least as great as that of typically developing
      children.

PMID- 15973310
TI  - A novel approach to managing variation: outpatient therapeutic monitoring of
      calcineurin inhibitor blood levels in liver transplant recipients.
AB  - OBJECTIVE: To apply the principles of statistical process control (SPC) to manage
      calcineurin inhibitor (CNI) blood levels. We hypothesized that the use of SPC
      would increase the proportion of CNI blood levels in the target range. STUDY
      DESIGN: The study population consisted of 217 patients more than 3 months after
      liver transplantation. After demonstration of proof of concept using the rapid
      cycle improvement process, SPC was applied to the entire population. The change
      package included definition of target ranges for CNI, implementation of a web
      based tool that displayed CNI blood levels on a control chart, and implementation
      of a protocol and a checklist for management of CNI blood levels. The principal
      outcome measure was the proportion of CNI blood levels in the target range.
      RESULTS: In the pilot study, the proportion of CNI blood levels in the target
      range increased from 50% to 85%. When the protocol was spread to the entire
      population, the proportion of drug levels in the target range increased to 77%
      from 50% (P < .001), whereas the range of CNI levels decreased. The rate of
      allograft rejection did not change. CONCLUSIONS: Utilization of SPC increased the
      proportion of CNI blood levels in target range. These observations may be
      applicable to the care of other chronic healthcare problems.

PMID- 15973311
TI  - Frequency of abnormal carbohydrate metabolism and diabetes in a population-based
      screening of adolescents.
AB  - OBJECTIVE: To document the frequency of glucose intolerance in adolescents in a
      population-based study of primarily African-American/Non-Hispanic whites in an
      urban-suburban school district. STUDY DESIGN: Measurement of fasting and 2-hour
      post-glucose load plasma glucose concentrations. RESULTS: Carbohydrate
      intolerance (either impaired fasting glucose, impaired glucose tolerance, or
      both) was identified in 8.0%, near-diabetes (1 fasting glucose > or = 126 mg/dL
      [7.0 mmol/L] and/or 2-hour glucose > or = 200 mg/dL [11.1 mmol/L]) in 0.3%, and
      diabetes in 0.36% (type 1A = 0.24%; type 2 = 0.08%; undiagnosed type 2 = 0.04%).
      A model for abnormal carbohydrate metabolism was constructed with regression
      analysis in the Carbohydrate Intolerance (CI)/near-diabetes group and with
      logistic regression in the entire study population. Risk factors for the
      development of CI/near-diabetes included having a 1 unit increase in body mass
      index (BMI) z-score and either being non-Hispanic white or in the pubertal group.
      Increased fasting glucose correlated with having puberty and decreased BMI z
      score, whereas 2-hour glucose correlated with increased BMI z-score. By using
      National Health and Nutrition Survey (NHANES) III (1988-1994) definitions,
      impaired fasting glucose was present in 2.0% in this study versus 1.7% (NHANES
      III). CONCLUSION: The prevalence of CI/near-diabetes was 8.3%. Undiagnosed
      diabetes mellitus was rare. One third of adolescents with diabetes mellitus could
      be classified as having type 2 diabetes mellitus. The adult model of the
      progression of insulin resistance to type 2 diabetes mellitus in adolescents may
      be valid. Despite the increase in the overweight population since NHANES III,
      abnormalities in glucose metabolism have not changed significantly.

PMID- 15973315
TI  - Speed of sound: relation to geometric characteristics of bone in children,
      adolescents, and adults.
AB  - OBJECTIVES: To investigate the relation between volumetric bone mineral density
      (vBMD) and speed of sound (SOS). STUDY DESIGN: Total and trabecular vBMD were
      measured by peripheral quantitative computed tomography at the forearm in a
      population of 216 individuals of a pediatric outpatient clinic. Moreover, SOS was
      measured by a quantitative ultrasound device (QUS) at the thumb, patella, and os
      calcis. RESULTS: Linear regression analysis revealed that the prediction of SOS
      by vBMD is relatively weak (R2 < 0.1). Moreover, body height and measures of bone
      size have a stronger influence on SOS than vBMD. The influence of bone size on
      SOS also depends on the location of measurement (highest prediction of SOS by
      body height at patella with R2 = 0.56). Anthropometric characteristics have a
      stronger influence on SOS than measures of bone mineral density at the thumb and
      patella in comparison to os calcis (body height predicts SOS at os calcis, with
      R2 = 0.03). Conclusions QUS is not a suitable method to assess bone density. If
      QUS is applied for the assessment of bone development and of bone fracture risk,
      the measurement should be performed with consideration of anthropometric
      measurements.

PMID- 15973313
TI  - Routine voiding cystourethrography is of no value in neonates with unilateral
      multicystic dysplastic kidney.
AB  - OBJECTIVES: To determine if two successive ultrasound examinations could rule out
      the presence of clinically significant contralateral anomalies in neonates with
      multicystic dysplastic kidney (MCDK), thereby avoiding unnecessary voiding
      cystourethrography (VCUG). STUDY DESIGN: We followed 76 newborn infants with
      antenatally discovered MCDK. Two successive neonatal renal ultrasound
      examinations were performed, one within the first week and one at around 1 month
      of life. VCUG and isotopic studies were performed in all infants. RESULTS:
      Urologic anomalies of the contralateral kidney were present in 19 of 76 children
      (25%): vesicoureteral reflux (VUR) in 16 (21%), ureteropelvic junction
      obstruction in 2 (3%), and renal duplex kidney in 1 (1%). Sixty-one infants (80%
      of total) had normal contralateral urinary tract on the 2 successive neonatal
      renal ultrasound scans. Among them, 4 of 61 (7%) infants presented with low-grade
      VUR on VCUG that had resolved spontaneously before 2 years of age. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of two successive ultrasound scans in the neonatal period to predict
      contralateral urological anomalies on VCUG were 75%, 95%, 80%, and 93%,
      respectively. CONCLUSIONS: In infants with antenatally diagnosed MCDK, two
      successive normal neonatal renal ultrasound scans will rule out clinically
      significant contralateral anomalies, thereby rendering the need for a neonatal
      VCUG unnecessary.

PMID- 15973316
TI  - Longitudinal changes in bone density in children and adolescents with moderate to
      severe cerebral palsy.
AB  - OBJECTIVE: To assess the natural history of "growth" in bone mineral density
      (BMD) in children and adolescents with moderate to severe cerebral palsy (CP).
      STUDY DESIGN: A prospective, longitudinal, observational study of BMD in 69
      subjects with moderate to severe spastic CP ages 2.0 to 17.7 years. Fifty-five
      subjects were observed for more than 2 years and 40 subjects for more than 3
      years. Each evaluation also included assessments of growth, nutritional status,
      Tanner stage, general health, and various clinical features of CP. RESULTS: Lower
      BMD z-scores at the initial evaluation were associated with greater severity of
      CP as judged by gross motor function and feeding difficulty, and with poorer
      growth and nutrition as judged by weight z-scores. BMD increased an average of 2%
      to 5%/y in the distal femur and lumbar spine, but ranged widely from +42%/y to 
      31%. In spite of increases in BMD, distal femur BMD z-scores decrease with age in
      this population. CONCLUSIONS: Children with severe CP develop over the course of
      their lives clinically significant osteopenia. Unlike elderly adults, this is not
      primarily from true losses in bone mineral, but from a rate of growth in bone
      mineral that is diminished relative to healthy children. The efficacy of
      interventions to increase BMD can truly be assessed only with a clear
      understanding of the expected changes in BMD without intervention.

PMID- 15973317
TI  - Bone densitometry in pediatric populations: discrepancies in the diagnosis of
      osteoporosis by DXA and CT.
AB  - OBJECTIVES: To test the hypothesis that because of errors associated with growth
      and development, osteoporosis is frequently overdiagnosed in children when using
      dual-energy x-ray absorptiometry (DXA). This study compared bone density values
      obtained by DXA with those from computed tomography (CT), which is not influenced
      by body or skeletal size. STUDY DESIGN: Vertebral bone density was measured by
      using both DXA and CT in 400 children (100 each, healthy and sick boys and
      girls). Regression analysis was used to compare DXA and CT Z scores, and the
      agreement between DXA and CT classifications of Z scores below -2.0 was examined.
      RESULTS: DXA and CT Z scores were moderately related (r2 = 0.55 after accounting
      for age and anthropometric measures). DXA Z scores predicted CT Z scores below 
      2.0 with reasonable sensitivity (72%), specificity (85%), and negative predictive
      value (98%), but positive predictive value was low (24%). Many more subjects were
      classified as having bone density lower by DXA (76/400) than by CT (25/400),
      particularly subjects below the 5 th percentile of height and/or weight for age.
      CONCLUSIONS: The inability of DXA to account for the large variability in
      skeletal size and body composition in growing children greatly diminishes the
      accuracy of this projection technique for assessing bone acquisition and
      diagnosing osteoporosis in pediatric populations.

PMID- 15973318
TI  - Neuropsychological and psychosocial function in children with a history of
      snoring or behavioral sleep problems.
AB  - OBJECTIVES: To compare neuropsychological and psychosocial function in children
      with a history of snoring, children with a history of behavioral sleep problems
      (BSP), children with both a history of snoring and BSP, and a group of control
      subjects. STUDY DESIGN: Families awaiting consultation for "sick" visits in 5
      general practice clinics completed the Sleep Disturbance Scale for Children. A
      subset of children were categorized into groups: Snorers (n = 11), BSP (n = 13),
      Snorers+BSP (n = 9), and controls (n = 31). Children underwent psychological
      (Wechsler Abbreviated Scale of Intelligence, Children's Memory Scale; Test of
      Everyday Attention and Auditory Continuous Performance Test) and psychosocial
      assessment (Child Behavior Checklist). RESULTS: With analysis of variance, it was
      revealed that, compared with children in the BSP and control groups, those in the
      Snorers+BSP and Snorers groups showed reduced intelligence and attention scores.
      By contrast, compared with children in the Snorers and control groups, children
      in the Snorers+BSP and BSP groups reported reduced social competency, increased
      problematic behavior, and reduced memory scores. Children in the combination of
      Snorers+BSP group showed more deficits than children in all other groups.
      CONCLUSION: In children, snoring and BSP, separately and together, are associated
      with impaired neuropsychological and psychosocial functioning. Furthermore,
      snoring and BSP are related to performance in disparate ways. Snoring was
      associated with intelligence and attention deficits, whereas BSP was associated
      with memory and behavioral deficits.

PMID- 15973319
TI  - Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of
      common tests.
AB  - OBJECTIVE: To compare the diagnostic accuracy of contrast enema (CE), anorectal
      manometry (ARM), and rectal suction biopsy (RSB) for the detection of
      Hirschsprung's disease (HD). STUDY DESIGN: Following a prospective protocol,
      infants suspected of HD underwent all 3 index tests. Children with positive
      results on 2 or more index tests or who continued to have severe bowel problems
      underwent a full thickness biopsy as reference standard. Clinical follow-up was
      the reference standard in all other children. RESULTS: Between 2000 and 2003, 111
      consecutive patients (67 boys; median age, 5.3 months) in whom HD was suspected
      were enrolled. HD was found in 28 patients. RSB had the highest sensitivity (93%)
      and specificity (100%) rates, but values were not significantly different from CE
      (sensitivity, 76%; specificity, 97%) or from ARM (sensitivity, 83%; specificity,
      93%). Inconclusive test results occurred in 8 infants with CE, in 15 infants with
      ARM because of agitation, and in 2 infants with RSB. CONCLUSION: RSB is the most
      accurate test for diagnosing HD, and it has the lowest rate of inconclusive test
      results.

PMID- 15973321
TI  - Satisfaction in different life domains in children receiving home parenteral
      nutrition and their families.
AB  - OBJECTIVE: To assess the quality-of-life (QOL) of children receiving home
      parenteral nutrition (HPN). STUDY DESIGN: A national multicenter study of 72
      patients (median age 4 years) presenting with a digestive disease requiring HPN,
      and 90 siblings, 67 fathers, and 69 mothers of these children. Median duration of
      HPN was 2 years (3 months-18 years). QOL was measured using validated, nondisease
      specific questionnaires appropriate to the children's ages. RESULTS: The QOL
      scores were high in patients of all ages and were not significantly different
      from scores in a reference population of healthy children and adolescents. Lower
      QOL scores were recorded in the domains related to hospital, health, doctors,
      medications, and obligations. The QOL was not affected in siblings but was
      significantly impaired in parents, especially in mothers, who showed a lower
      level of satisfaction than did fathers for items related to work, inner life, and
      freedom. Presence of an ileostomy was the only factor that influenced QOL,
      especially of adolescents. CONCLUSIONS: QOL of HPN-dependent children and
      siblings is not different from that of healthy children, suggesting that these
      children actively use effective coping strategies. In contrast, the QOL of
      parents of HPN-dependent children is low.

PMID- 15973323
TI  - Endothelin-1 in human intestine resected for necrotizing enterocolitis.
AB  - OBJECTIVES: We asked if the tissue concentration of the potent vasoconstrictor
      endothelin-1 (ET-1) is greater in areas of human preterm intestine that
      demonstrate histologic evidence of necrotizing enterocolitis (NEC) when compared
      with relatively healthy areas within the same resection specimen. We then
      evaluated if ET-1 participates in hemodynamic regulation within intestinal
      subserosal arterioles harvested from portions of human preterm intestine that
      demonstrate NEC. STUDY DESIGN: Human preterm intestine resected for NEC was
      divided into three zones based on proximity to the perforation (zone 1 most
      proximal, zone 3 most distal). Histologic evidence of NEC was determined in each
      zone (normal = 0, advanced necrosis = 6). The tissue concentration of ET-1 was
      determined by enzyme-linked immunosorbent assay within intestinal homogenates
      prepared from each zone. Arteriolar hemodynamics were determined in vitro on
      subserosal arterioles harvested from different zones. Arteriolar flow rate,
      diameter, and resistance were determined at pressure gradients (DeltaP) of 20 and
      40 mmHg under control conditions and again after blockade of endothelin ET A
      receptors with BQ610 (10 -9 mol/L). RESULTS: The tissue concentration of ET-1
      (pg/mg protein) and histologic score in the three zones were: zone 1: 84 +/- 14,
      5.5 +/- 0.3; zone 2: 99 +/- 12, 4.7 +/- 0.4, and zone 3: 33 +/- 9, 0.8 +/- 0.6,
      respectively (M +/- SD, n = 10 resection specimens, P < .05, zone 3 vs zones 1
      and 2). Zone 2 arterioles demonstrated significantly lower flow rate and diameter
      and increased resistance under control conditions than zone 3 arterioles when
      DeltaP was either 20 or 40 mmHg (n = 7, P < .05). Treatment with BQ610 had no
      effect on zone 3 arterioles but significantly vasodilated zone 2 arterioles,
      increasing flow rate and vessel diameter, and decreasing vascular resistance (n =
      7, P < .05). CONCLUSIONS: The tissue concentration of ET-1 is greater in human
      preterm intestine that demonstrates histologic evidence of NEC. Arterioles
      harvested from intestine exhibiting histologic evidence of NEC demonstrate
      vasoconstriction when compared with arterioles from relatively healthy intestine
      in the same resection specimen. This vasoconstriction was reversed by blockade of
      endothelin ET A receptors.

PMID- 15973322
TI  - Extremely low birthweight neonates with protracted ventilation: mortality and 18
      month neurodevelopmental outcomes.
AB  - OBJECTIVE: To compare duration of ventilation to mortality and adverse
      neurodevelopmental outcomes among extremely low birth weight (ELBW; 501-1000 g)
      infants. STUDY DESIGN: Retrospective analysis of prospectively collected data
      from 5364 infants with a birthweight of 501 to 1000 g born at National Institute
      of Child Health and Human Development (NICHD) Neonatal Research Network centers
      from 1995 to 1998. The main outcome measures were: survival, duration of
      mechanical ventilation, and neurodevelopmental outcome. RESULTS: Overall survival
      was 71%. The median duration of ventilation for survivors was 23 days; 75% were
      free of mechanical ventilation by 39 days, and 7% were ventilated for > or = 60
      days. Of those ventilated for > or = 60 days, 24% survived without impairment. Of
      those ventilated for > or = 90 days, only 7% survived without impairment. Of
      those ventilated > or = 120 days, all survivors were impaired. CONCLUSIONS: The
      prognosis for ELBW with protracted ventilation remains grim. The cohort who
      remain intubated have diminished survival and high rates of impairment. Parents
      of these infants should be informed of changes in prognosis as the time of
      ventilation increases.

PMID- 15973324
TI  - Neonatal renal venous thrombosis: clinical outcomes and prevalence of
      prothrombotic disorders.
AB  - OBJECTIVE: To determine clinical outcomes and the prevalence of prothrombotic
      conditions in patients who had neonatal renal venous thrombosis (RVT). STUDY
      DESIGN: A retrospective cohort of neonates with RVT who were admitted to 4
      pediatric centers from 1980 to 2001 was identified. Information on clinical
      presentation, laboratory and radiological investigation, and treatment were
      abstracted. Survivors were evaluated for renal status and prothrombotic
      conditions. RESULTS: Forty-three patients with neonatal RVT were identified. RVT
      was unilateral in 24 patients (56%) and associated with 2thrombi at other sites
      in 32 patienets (74%). Clinical presentations included renal failure in 24
      patients (56%), thrombocytopenia, anemia, or both in 22 patients (51%), and renal
      mass in 21 patients (49%). Neonatal interventions included anti-coagulants in 28
      patients (65%), antihypertensive medications in 9 patients (21%), peritoneal
      dialysis in 2 patients (5%), and nephrectomy in 2 patients (5%). The median age
      at follow-up was 3.7 years (range, 0.5-20.2 years). Thirteen patients (34%) had
      hypertension, and 11 patients (29%) had renal failure. End-stage renal disease
      developed in 3 patients, and they underwent live-related renal transplants.
      Twelve of the 28 patients (43%) examined had prothrombotic abnormalities.
      CONCLUSION: Neonatal RVT is associated with significant renal morbidity and a
      high prevalence of prothrombotic abnormalities.

PMID- 15973325
TI  - Congenital cytomegalovirus infection: association between virus burden in infancy
      and hearing loss.
AB  - OBJECTIVE: To determine the relationship between the virus burden in infancy and
      hearing loss in congenital CMV infection. STUDY DESIGN: A cohort of 76 infants
      with congenital cytomegalovirus (CMV) infection identified by means of newborn
      virologic screening was monitored for outcome. The amount of infectious CMV was
      analyzed in urine specimens obtained during early infancy. Peripheral blood (PB)
      samples obtained during early infancy were available from 75 children and CMV DNA
      was quantitated with a real-time quantitative polymerase chain reaction. RESULTS:
      Infants with clinical abnormalities at birth (symptomatic congenital CMV
      infection) had higher amounts of CMV in urine (P = .005) and CMV DNA in PB (P =
      .001) than infants with no symptoms. Eight children with and 4 children without
      symptoms had hearing loss. Among children without symptoms, those with hearing
      loss had a significantly greater amount of CMV in urine (P = .03) and PB virus
      burden (P = .02) during infancy than those with normal hearing. Infants with < 5
      x 10(3) pfu/mL of urine CMV and infants with < 1 x 10(4) copies/mL of viral DNA
      in PB were at a lower risk for hearing loss. CONCLUSION: In children with
      asymptomatic congenital CMV infection, hearing loss was associated with increased
      amounts of urine CMV and PB CMV DNA during early infancy.

PMID- 15973327
TI  - The sibling center: a pilot program for siblings of children and adolescents with
      a serious medical condition.

PMID- 15973326
TI  - Fatty Acid ethyl esters: quantitative biomarkers for maternal alcohol
      consumption.
AB  - OBJECTIVE: To develop a laboratory marker to identify newborns exposed to
      alcohol. STUDY DESIGN: Meconium was collected from 30 infants from Jordan who
      were unexposed and from 248 Cleveland study infants of varying exposure status.
      Retrospective maternal alcohol histories were obtained. Fatty acid ethyl esters
      (FAEEs) were quantified with gas chromatography/flame ionization and compared
      between abstainers and non-abstainers to identify FAEEs of interest. The area
      under the receiver operating characteristic curve, sensitivity, specificity, and
      positive and negative predictive values were calculated by using definitions of
      drinking obtained from a graphical representation. RESULTS: Six of 7 FAEEs were
      significantly different between the non-abstainers and at least 1 of 2 of the
      abstaining groups. FAEEs best predicted drinks per drinking day, and ethyl
      linoleate had the greatest area under the curve (76%), with a sensitivity rate of
      88%, a specificity rate of 64%, a positive predictive value of 9%, and a negative
      predictive value of 99%. No combination of FAEEs was better than a single ester
      for identifying drinkers. CONCLUSION: Ethyl linoleate in meconium is a useful
      biological marker for identifying infants not exposed in utero to high levels of
      alcohol in a high-risk, substance-abusing, clinic-based sample.

PMID- 15973328
TI  - Herpes simplex virus type 2 acute retinal necrosis 9 years after neonatal herpes.
AB  - Many cases of acute retinal necrosis caused by HSV-2 have been reported in
      children, teenagers, and young adults as a result of reactivation of congenital
      or neonatal infections, which may have been subclinical. Pediatricians should be
      aware of this entity and alert to recurrences that may be delayed by years.

PMID- 15973329
TI  - Detection of autoimmune regulator gene mutations in children with type 2
      autoimmune hepatitis and extrahepatic immune-mediated diseases.
AB  - Autoimmune regulator gene mutations were identified in 3 children with type 2
      autoimmune hepatitis and extrahepatic immune diseases, including 1 child with
      immune hepatitis recurrence after liver transplantation. These findings suggest
      that autoimmune regulator gene variants might predispose children to systemic
      autoimmune disease, a recurrence of immune disease, or both.

PMID- 15973330
TI  - Frasier syndrome comes full circle: genetic studies performed in an original
      patient.
AB  - Frasier syndrome is a relatively rare disorder associated with XY gonadal
      dysgenesis, gonadoblastoma, and kidney failure. In this report, we identify a
      classic mutation in the Wilms' tumor 1 gene in one of the original cases of
      Frasier syndrome reported in this Journal in 1964.

PMID- 15973331
TI  - Trap-door sternum in sickle cell disease.

PMID- 15973332
TI  - Inadequacy of IV vitamin A supplementation of extremely preterm infants?

PMID- 15973334
TI  - Isolation and bronchiolitis.

PMID- 15973336
TI  - Inadequacy of IV vitamin A supplementation of extremely preterm infants?

PMID- 15973337
TI  - The normality of depression.

PMID- 15973338
TI  - Treating depression in the elderly: an update on antidepressants.

PMID- 15973339
TI  - Depression--the diet connection.

PMID- 15973340
TI  - Recognizing late-life depression: why is this important for nurses in the home
      setting?

PMID- 15973341
TI  - Caregiver, take care.
AB  - Becoming a caregiver is a time of transition that requires a restructuring of
      one's goals, behaviors, and responsibilities. Although the individual
      circumstances that bring one to the caregiver's role may differ, one thing is
      certain--no one comes to the job prepared for the task. No matter how difficult
      the role, however, becoming a caregiver can give birth to new skills, new
      strengths, and new friends and contacts. Being able to cope with the stress of
      being a caregiver is part of the art of caregiving.

PMID- 15973342
TI  - Spiritual well-being and caregiver burden in Alzheimer's caregivers.
AB  - The purpose of this study was to examine the relationship between spiritual well
      being and caregiver burden in family caregivers of persons with Alzheimer's
      disease. A descriptive, correlational research design was used, and a convenience
      sample of 150 caregivers was surveyed (71 African Americans, 77 Caucasians, and 2
      other caregivers). Descriptive statistics were used to examine selected caregiver
      demographics. Statistical analysis included bivariate correlations using the
      Pearson product-moment coefficient correlation. The study's research question was
      as follows: What is the relationship between spiritual well-being and caregiver
      burden? It was hypothesized that there would be an inverse relationship between
      the 2 variables. A statistically significance inverse relationship (R = -.493, P
      < or = .01) was found to exist between the variables, thereby supporting the
      study's hypothesis. Additional findings revealed significant differences in
      African American and Caucasian caregiver's perception of spiritual well-being and
      caregiver burden. Caregivers also reported frequent use of spiritual behaviors or
      practices such as prayer. Findings implicate the need for further investigation
      and development of culturally relevant caregiver intervention strategies and
      programs that incorporate spirituality as a core component.

PMID- 15973343
TI  - The important lessons: Sylvester and Ilene.

PMID- 15973344
TI  - Research review: the effect of acupressure with massage on fatigue and depression
      in patients with end-stage renal disease.

PMID- 15973345
TI  - Psychosocial consequences of prostate cancer: 30 years of research.
AB  - Carcinoma of the prostate is the leading source of solid-organ cancer in U.S.
      men. When the disease is discovered early, survival rates are high; survivorship,
      however, is commonly complicated by disease-specific treatment side effects that
      challenge a man's physical, mental, and social well-being and life satisfaction.
      This review comprises a search of scientific literature published between 1970
      and March 2004 with the aims of 1) identifying the terms used to define the
      psychosocial consequences unique to men treated for prostate cancer and 2)
      describing the research aimed at improving the lives of survivors through
      psychosocial interventions.

PMID- 15973346
TI  - Identifying and managing acute alcohol withdrawal in the elderly.
AB  - In the elderly population, alcohol-related problems may be misinterpreted as
      normal consequences of aging. However, alcohol is a commonly abused substance
      among older adults, and age-related changes predispose these patients to a
      greater sensitivity to its effects. All older patients should be screened for
      alcohol dependence and abuse on admission to an acute care facility. If
      identified, the plan of care must include close observation for acute alcohol
      withdrawal and prompt intervention if it occurs.

PMID- 15973347
TI  - Testing the feasibility and initial effects of iron and vitamin C to enhance
      nursing home residents' immune status following an influenza vaccine.
AB  - Influenza infections pose a serious threat to residents living in nursing homes
      and are a major cause of morbidity and mortality in older adults. It is estimated
      that influenza vaccination is only 30%-40% effective in the frail elderly. This 2
      group experimental design study examined the efficacy of giving iron supplements
      to nursing home residents aged 65 and older to improve immune response following
      influenza vaccination. Specific aims of the study were to test study procedures
      and explore initial immune response. A number of barriers were encountered during
      the recruitment and consent phase limiting subject recruitment. Only serum
      transferrin was significantly different following the 30-day administration of
      iron supplementation. It was concluded that to achieve sufficient power to
      examine the effect of the intervention on immune response and infection rates,
      aggressive recruiting strategies at multiple sites are necessary.

PMID- 15973348
TI  - Pharmacology update: depression.

PMID- 15973349
TI  - Research review: exercise interventions for treatment of depression.

PMID- 15973350
TI  - Geriatric nurse practitioner guideline: periodontal disease in older adults.

PMID- 15973351
TI  - Oxidative metabolism in cultured rat astroglia: effects of reducing the glucose
      concentration in the culture medium and of D-aspartate or potassium stimulation.
AB  - The glucose concentration in the culture medium may affect the energy metabolism
      of cultured cells. The oxidative metabolism of glucose in astrocytes might also
      be affected because the glucose concentration (25 mmol/L) of many culture media
      is higher than the physiological levels (approximately 3 mmol/L). In the present
      study, we assessed the effects of reducing the glucose concentration in the
      culture medium on the oxidative metabolism of glucose in cultured rat astroglia
      by measuring the oxidation rates of L-[U-14C]lactate or D-[U-14C]glucose to
      14CO2. The effects of D-aspartate and elevated extracellular K+ levels on
      oxidative and glycolytic metabolism in astroglia were also investigated. The
      rates of [14C]lactate and [14C]glucose oxidation in astroglia cultured in a
      medium containing 2 mmol/L of glucose (astroglia2) were approximately twofold of
      those in astroglia cultured in a medium containing 22 mmol/L of glucose
      (astroglia22). D-Aspartate (500 micromol/L) significantly increased [14C]lactate
      oxidation by 156% in astroglia22 and by 83% in astroglia2. D-[U-14C]glucose
      oxidation in astroglia22 and astroglia2 was also increased by 94% and 76%,
      respectively. In contrast, an elevated extracellular K+ concentration (7.4
      mmol/L) did not affect glucose and lactate oxidation, although it increased 2
      deoxy-D-[1-14C]glucose phosphorylation. Astroglia grown in the physiological
      glucose concentration are more dependent on the oxidative metabolism of glucose
      than that in high-glucose concentration. Glucose concentration in culture medium
      has a strong influence on astrocytic oxidative capacity in vitro.

PMID- 15973352
TI  - Lactate: the ultimate cerebral oxidative energy substrate?
AB  - Research over the past two decades has renewed the interest in lactate, no longer
      as a useless end product of anaerobic glycolysis in brain (and other tissues),
      but as an oxidative substrate for energy metabolism. While this topic would be
      considered blasphemy only three decades ago, much recent evidence indicates that
      lactate does play a major role in aerobic energy metabolism in the brain, the
      heart, skeletal muscle, and possibly in any other tissue and organ. Nevertheless,
      this concept has challenged the old dogma and ignited a fierce debate, especially
      among neuroscientists, pitting the supporters of glucose as the major oxidative
      energy substrate against those who support lactate as a possible alternative to
      glucose under certain conditions. Meanwhile, researchers working on energy
      metabolism in skeletal muscle have taken great strides toward bridging between
      these two extreme positions, while avoiding the high decibels of an emotional
      debate. Employing their findings along with the existing old and new data on
      cerebral energy metabolism, it is postulated here that lactate is the only major
      product of cerebral (and other tissues) glycolysis, whether aerobic or anaerobic,
      neuronal or astrocytic, under rest or during activation. Consequently, this
      postulate entails that lactate is a major, if not the only, substrate for the
      mitochondrial tricarboxylic acid cycle. If proven true, this hypothesis could
      provide better understanding of the biochemistry and physiology of (cerebral)
      energy metabolism, while holding important implications in the field of
      neuroimaging. Concomitantly, it could satisfy both 'glucoseniks' and 'lactatians'
      in the ongoing debate.

PMID- 15973353
TI  - A multiparametric assessment of oxygen efflux from the brain.
AB  - A quantitative understanding of unidirectional versus net extraction of oxygen in
      the brain is required because an important factor in calculating oxidative
      metabolism by calibrated functional magnetic resonance imaging (fMRI) as well as
      oxygen inhalation methods of positron emission tomography (15O2-PET) and nuclear
      magnetic resonance (17O2-NMR)) is the degree of oxygen efflux from the brain back
      into the blood. Because mechanisms of oxygen transport from blood to brain are
      dependent on cerebral metabolic rate of oxygen consumption (CMRO2), cerebral
      blood flow (CBF), and oxygen partial pressure (pO2) values in intravascular (Piv)
      and extravascular (Pev) compartments, we implemented multimodal measurements of
      these parameters into a compartmental model of oxygen transport and metabolism
      (i.e., hemoglobin-bound oxygen, oxygen dissolved in plasma and tissue spaces,
      oxygen metabolized in the mitochondria). In the alpha-chloralose anesthetized rat
      brain, we used magnetic resonance (7.0 T) and fluorescence quenching methods to
      measure CMRO2 (2.5+/-1.0 micromol/g min), CBF (0.7+/-0.2 mL/g min), Piv (74+/-10
      mm Hg), and Pev (16+/-5 mm Hg) to estimate the degree of oxygen efflux from the
      brain. In the axially distributed compartmental model, oxygen molecules in blood
      had two possible fates: enter the tissue space or remain in the same compartment;
      while in tissue there were three possible fates: enter the blood or the
      mitochondrial space, or remain in the same compartment. The multiparametric
      results indicate that the probability of unmetabolized (i.e., dissolved) oxygen
      molecules reentering the blood from the tissue is negligible and thus its
      inclusion may unnecessarily complicate calculations of CMRO2 for 15O-PET, 17O
      NMR, and calibrated fMRI methods.

PMID- 15973354
TI  - Sequential versus nonsequential measurement of density and affinity of dopamine
      D2 receptors with [11C]raclopride: 2: effects of DAT inhibitors.
AB  - The multiple ligand concentration receptor assays (MLCRA) method allows, in a
      stable condition, reliable and reproducible measurements of the density and
      affinity of the dopamine (DA) D2 receptors with [11C]raclopride, using either a
      sequential method (two or more scans in one day) or a nonsequential method (two
      or more scans over days or weeks). We have shown that measurement of receptor
      density and affinity is also possible after an acute pharmacological challenge
      with methamphetamine and that both scanning protocols yield similar values.
      However, our attempts to measure receptor density and affinity after a
      pharmacological challenge with another class of drugs that lead to the same
      outcome, increase in synaptic DA concentrations, revealed opposite results with
      the two scanning methods: a decrease in receptor density with the sequential
      method and an increase in affinity with a nonsequential method. These results
      show the impact of the time-dependency of the effects of an 'acute'
      pharmacological challenge on MLCRA studies. A theoretical simulation is presented
      to account for the discrepancy in the sequential and nonsequential data. A
      possible alternate scanning paradigm is proposed to avoid the confounding effect
      of time variability of the endogenous ligand synaptic concentrations in the
      sequential condition.

PMID- 15973355
TI  - Abeta25-35 alters Akt activity, resulting in Bad translocation and mitochondrial
      dysfunction in cerebrovascular endothelial cells.
AB  - The amyloid-beta peptide (Abeta) induces apoptosis in cerebrovascular endothelial
      cells (CECs), contributing to the pathogenesis of cerebral amyloid angiopathy. We
      have previously shown that Abeta induces apoptosis in CECs. In the present study,
      we report that Abeta25-35-induced CEC apoptosis involves the inactivation of Akt,
      a signaling kinase important in maintaining cell viability. Akt prevents the
      activation of death-signaling events by facilitating the inactivation of
      proapoptotic proteins such as Bad. We applied three strategies to show that
      Abeta25-35 inactivation of Akt is causally related to Abeta25-35-induced CEC
      death by preventing Bad activation and subsequent mitochondrial dysfunction
      (reflected by the release of endonuclease G and Smac, two proapoptotic
      intermembranous proteins of the mitochondria). Wortmannin, a PI3-kinase
      inhibitor, enhanced Abeta25-35-induced Bad activation, mitochondrial dysfunction
      and CEC death. Enhancement of Akt activity by a Tat-Akt fusion protein, or by
      viral gene transfer of a constitutively active mutant of akt, reduced Bad
      activation, mitochondrial dysfunction, and CEC death. Using a siRNA strategy to
      knock down the bad gene, we showed that Bad activation is causally related to
      Abeta25-35-induced mitochondrial dysfunction and CEC death. Together, these
      results establish that the Akt-Bad cascade is altered by Abeta25-35, resulting in
      CEC apoptosis.

PMID- 15973358
TI  - Contact force measurements and stress-induced anisotropy in granular materials.
AB  - Interparticle forces in granular media form an inhomogeneous distribution of
      filamentary force chains. Understanding such forces and their spatial
      correlations, specifically in response to forces at the system boundaries,
      represents a fundamental goal of granular mechanics. The problem is of relevance
      to civil engineering, geophysics and physics, being important for the
      understanding of jamming, shear-induced yielding and mechanical response. Here we
      report measurements of the normal and tangential grain-scale forces inside a two
      dimensional system of photoelastic disks that are subject to pure shear and
      isotropic compression. Various statistical measures show the underlying
      differences between these two stress states. These differences appear in the
      distributions of normal forces (which are more rounded for compression than
      shear), although not in the distributions of tangential forces (which are
      exponential in both cases). Sheared systems show anisotropy in the distributions
      of both the contact network and the contact forces. Anisotropy also occurs in the
      spatial correlations of forces, which provide a quantitative replacement for the
      idea of force chains. Sheared systems have long-range correlations in the
      direction of force chains, whereas isotropically compressed systems have short
      range correlations regardless of the direction.

PMID- 15973356
TI  - TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene
      silencing.
AB  - MicroRNAs (miRNAs) are generated by a two-step processing pathway to yield RNA
      molecules of approximately 22 nucleotides that negatively regulate target gene
      expression at the post-transcriptional level. Primary miRNAs are processed to
      precursor miRNAs (pre-miRNAs) by the Microprocessor complex. These pre-miRNAs are
      cleaved by the RNase III Dicer to generate mature miRNAs that direct the RNA
      induced silencing complex (RISC) to messenger RNAs with complementary sequence.
      Here we show that TRBP (the human immunodeficiency virus transactivating response
      RNA-binding protein), which contains three double-stranded, RNA-binding domains,
      is an integral component of a Dicer-containing complex. Biochemical analysis of
      TRBP-containing complexes revealed the association of Dicer-TRBP with Argonaute 2
      (Ago2), the catalytic engine of RISC. The physical association of Dicer-TRBP and
      Ago2 was confirmed after the isolation of the ternary complex using Flag-tagged
      Ago2 cell lines. In vitro reconstitution assays demonstrated that TRBP is
      required for the recruitment of Ago2 to the small interfering RNA (siRNA) bound
      by Dicer. Knockdown of TRBP results in destabilization of Dicer and a consequent
      loss of miRNA biogenesis. Finally, depletion of the Dicer-TRBP complex via
      exogenously introduced siRNAs diminished RISC-mediated reporter gene silencing.
      These results support a role of the Dicer-TRBP complex not only in miRNA
      processing but also as a platform for RISC assembly.

PMID- 15973359
TI  - Plant communities: ecosystem stability in Inner Mongolia.
AB  - Bai et al. suggest that in China's Inner Mongolia steppe, community-level
      stability arises from compensatory effects among the principal components at both
      the species and plant functional group (PFG) levels. By analysing a consistent 19
      year data set (1980-98), we show here that their analysis of a 24-year field data
      set (1980-2003) is called into question by inconsistencies in sampling location
      and numbers after 1998; the authors' findings are further undermined because they
      do not distinguish temporal variation from spatial heterogeneity in analysing
      compensatory effects among species or PFGs. We believe that rigorous reanalysis
      is needed for a better understanding of grassland stability.

PMID- 15973361
TI  - Plant communities: ecosystem maturity and performance.
AB  - The effect of maturity, or successional stage, on ecosystem performance (measured
      as productivity or stability, for example) is important for both basic ecology
      and ecosystem management. On the basis of the results of a long-term study of two
      different plant communities at two sites in the Inner Mongolia grassland, Bai et
      al. claim that these communities simultaneously achieve high species richness,
      productivity and ecosystem stability at the late successional stage. However, I
      question their interpretation of the data and suggest that this claim is
      undermined by evidence from other empirical and theoretical studies.

PMID- 15973362
TI  - Not-so-deep impact.

PMID- 15973363
TI  - In praise of soft science.

PMID- 15973364
TI  - Toyota on a roll.

PMID- 15973366
TI  - Trouble brews over contested trend in hurricanes.

PMID- 15973367
TI  - Drug targeting: is race enough?

PMID- 15973368
TI  - China's chicken farmers under fire for antiviral abuse.

PMID- 15973369
TI  - Databases in peril.

PMID- 15973370
TI  - Earth holds comet smash in its sights.

PMID- 15973371
TI  - Bill on deep-sea fish farms brings wave of disapproval.

PMID- 15973373
TI  - Retracted papers damage work on DNA repair.

PMID- 15973375
TI  - A trip of a lifetime.

PMID- 15973376
TI  - Back to our roots.

PMID- 15973378
TI  - Toyota's production line leads from lab to road.

PMID- 15973377
TI  - Dalton Conley profile: harder than rocket science.

PMID- 15973381
TI  - Sale of public databases puts biological data at risk.

PMID- 15973382
TI  - No political agenda in academic bill of rights.

PMID- 15973383
TI  - Turkish research council is proud of its independence.

PMID- 15973387
TI  - Dynamic universe.

PMID- 15973388
TI  - Low-temperature physics: a quantum revolution.

PMID- 15973390
TI  - Earth science: new Madrid in motion.

PMID- 15973389
TI  - Neuroscience: friends and grandmothers.

PMID- 15973392
TI  - Evolutionary biology: Island of the clones.

PMID- 15973393
TI  - Animal behaviour: Congo's art.

PMID- 15973394
TI  - Consciousness: Crick and the claustrum.

PMID- 15973395
TI  - Granular matter: a tale of tails.

PMID- 15973396
TI  - Neuroscience: an intrusive chaperone.

PMID- 15973397
TI  - Obituary: Fred S. Rosen (1930-2005).

PMID- 15973398
TI  - Surface tension: floater clustering in a standing wave.
AB  - How do waves affect the distribution of small particles that float on water? Here
      we show that drifting small particles concentrate in either the nodes or
      antinodes of a standing wave, depending on whether they are hydrophilic or
      hydrophobic, as a result of a surface-tension effect that violates Archimedes'
      law of buoyancy. This clustering on waves may find practical application in
      particle separation and provides insight into the patchy distribution on water
      of, for example, plastic litter or oil slicks.

PMID- 15973399
TI  - Biodiversity: disease threat to European fish.
AB  - The deliberate introduction of new species can have unexpected negative
      consequences and we show here how a recently introduced fish, the invasive Asian
      cyprinid Pseudorasbora parva, is causing increased mortality and totally
      inhibiting spawning in an already endangered native fish, the European cyprinid
      Leucaspius delineatus. This threat is caused by an infectious pathogen, a rosette
      like intracellular eukaryotic parasite that is a deadly, non-specific agent. It
      is probably carried by healthy Asian fish, and could decrease fish biodiversity
      in Europe, as well as having implications for commercial aquaculture.

PMID- 15973400
TI  - Vortices and superfluidity in a strongly interacting Fermi gas.
AB  - Quantum degenerate Fermi gases provide a remarkable opportunity to study strongly
      interacting fermions. In contrast to other Fermi systems, such as
      superconductors, neutron stars or the quark-gluon plasma of the early Universe,
      these gases have low densities and their interactions can be precisely controlled
      over an enormous range. Previous experiments with Fermi gases have revealed
      condensation of fermion pairs. Although these and other studies were consistent
      with predictions assuming superfluidity, proof of superfluid behaviour has been
      elusive. Here we report observations of vortex lattices in a strongly
      interacting, rotating Fermi gas that provide definitive evidence for
      superfluidity. The interaction and therefore the pairing strength between two 6Li
      fermions near a Feshbach resonance can be controlled by an external magnetic
      field. This allows us to explore the crossover from a Bose-Einstein condensate of
      molecules to a Bardeen-Cooper-Schrieffer superfluid of loosely bound pairs. The
      crossover is associated with a new form of superfluidity that may provide
      insights into high-transition-temperature superconductors.

PMID- 15973402
TI  - A planetary system as the origin of structure in Fomalhaut's dust belt.
AB  - The Sun and >15 per cent of nearby stars are surrounded by dusty disks that must
      be collisionally replenished by asteroids and comets, as the dust would otherwise
      be depleted on timescales <10(7) years (ref. 1). Theoretical studies show that
      the structure of a dusty disk can be modified by the gravitational influence of
      planets, but the observational evidence is incomplete, at least in part because
      maps of the thermal infrared emission from the disks have low linear resolution
      (35 au in the best case). Optical images provide higher resolution, but the
      closest examples (AU Mic and beta Pic) are edge-on, preventing the direct
      measurement of the azimuthal and radial disk structure that is required for
      fitting theoretical models of planetary perturbations. Here we report the
      detection of optical light reflected from the dust grains orbiting Fomalhaut (HD
      216956). The system is inclined 24 degrees away from edge-on, enabling the
      measurement of disk structure around its entire circumference, at a linear
      resolution of 0.5 au. The dust is distributed in a belt 25 au wide, with a very
      sharp inner edge at a radial distance of 133 au, and we measure an offset of 15
      au between the belt's geometric centre and Fomalhaut. Taken together, the sharp
      inner edge and offset demonstrate the presence of planetary-mass objects orbiting
      Fomalhaut.

PMID- 15973403
TI  - Timescales of shock processes in chondritic and martian meteorites.
AB  - The accretion of the terrestrial planets from asteroid collisions and the
      delivery to the Earth of martian and lunar meteorites has been modelled
      extensively. Meteorites that have experienced shock waves from such collisions
      can potentially be used to reveal the accretion process at different stages of
      evolution within the Solar System. Here we have determined the peak pressure
      experienced and the duration of impact in a chondrite and a martian meteorite,
      and have combined the data with impact scaling laws to infer the sizes of the
      impactors and the associated craters on the meteorite parent bodies. The duration
      of shock events is inferred from trace element distributions between coexisting
      high-pressure minerals in the shear melt veins of the meteorites. The shock
      duration and the associated sizes of the impactor are found to be much greater in
      the chondrite (approximately 1 s and 5 km, respectively) than in the martian
      meteorite (approximately 10 ms and 100 m). The latter result compares well with
      numerical modelling studies of cratering on Mars, and we suggest that martian
      meteorites with similar, recent ejection ages (10(5) to 10(7) years ago) may have
      originated from the same few square kilometres on Mars.

PMID- 15973401
TI  - A structural basis for allosteric control of DNA recombination by lambda
      integrase.
AB  - Site-specific DNA recombination is important for basic cellular functions
      including viral integration, control of gene expression, production of genetic
      diversity and segregation of newly replicated chromosomes, and is used by
      bacteriophage lambda to integrate or excise its genome into and out of the host
      chromosome. lambda recombination is carried out by the bacteriophage-encoded
      integrase protein (lambda-int) together with accessory DNA sites and associated
      bending proteins that allow regulation in response to cell physiology. Here we
      report the crystal structures of lambda-int in higher-order complexes with
      substrates and regulatory DNAs representing different intermediates along the
      reaction pathway. The structures show how the simultaneous binding of two
      separate domains of lambda-int to DNA facilitates synapsis and can specify the
      order of DNA strand cleavage and exchange. An intertwined layer of amino-terminal
      domains bound to accessory (arm) DNAs shapes the recombination complex in a way
      that suggests how arm binding shifts the reaction equilibrium in favour of
      recombinant products.

PMID- 15973404
TI  - Structural signature of jamming in granular media.
AB  - Glasses are rigid, but flow when the temperature is increased. Similarly,
      granular materials are rigid, but become unjammed and flow if sufficient shear
      stress is applied. The rigid and flowing phases are strikingly different, yet
      measurements reveal that the structures of glass and liquid are virtually
      indistinguishable. It is therefore natural to ask whether there is a structural
      signature of the jammed granular state that distinguishes it from its flowing
      counterpart. Here we find evidence for such a signature, by measuring the contact
      force distribution between particles during shearing. Because the forces are
      sensitive to minute variations in particle position, the distribution of forces
      can serve as a microscope with which to observe correlations in the positions of
      nearest neighbours. We find a qualitative change in the force distribution at the
      onset of jamming. If, as has been proposed, the jamming and glass transitions are
      related, our observation of a structural signature associated with jamming hints
      at the existence of a similar structural difference at the glass transition-
      presumably too subtle for conventional scattering techniques to uncover. Our
      measurements also provide a determination of a granular temperature that is the
      counterpart in granular systems to the glass-transition temperature in liquids.

PMID- 15973405
TI  - Space geodetic evidence for rapid strain rates in the New Madrid seismic zone of
      central USA.
AB  - In the winter of 1811-1812, near the town of New Madrid in the central United
      States and more than 2,000 km from the nearest plate boundary, three earthquakes
      within three months shook the entire eastern half of the country and liquefied
      the ground over distances far greater than any historic earthquake in North
      America. The origin and modern significance of these earthquakes, however, is
      highly contentious. Geological evidence demonstrates that liquefaction due to
      strong ground shaking, similar in scale to that generated by the New Madrid
      earthquakes, has occurred at least three and possibly four times in the past
      2,000 years (refs 4-6), consistent with recurrence statistics derived from
      regional seismicity. Here we show direct evidence for rapid strain rates in the
      area determined from a continuously operated global positioning system (GPS)
      network. Rates of strain are of the order of 10(-7) per year, comparable in
      magnitude to those across active plate boundaries, and are consistent with known
      active faults within the region. These results have significant implications for
      the definition of seismic hazard and for processes that drive intraplate
      seismicity.

PMID- 15973406
TI  - First evidence of a venom delivery apparatus in extinct mammals.
AB  - Numerous non-mammalian vertebrates have evolved lethal venoms to aid either in
      securing prey or as protection from predators, but modern mammals that use venoms
      in these ways are rare, including only the duck-billed platypus
      (Ornithorhynchus), the Caribbean Solenodon, and a few shrews (Soricidae) (Order
      Insectivora). Here we report evidence of a venom delivery apparatus in extinct
      mammals, documented by well-preserved specimens recovered from late Palaeocene
      rocks in Alberta, Canada. Although classified within Eutheria, these mammals are
      phylogenetically remote from modern Insectivora and have evolved specialized
      teeth as salivary venom delivery systems (VDSs) that differ markedly from one
      another and from those of Solenodon and shrews. Our discoveries therefore show
      that mammals have been much more flexible in the evolution of VDSs than
      previously believed, contradicting currently held notions that modern
      insectivorans are representative of the supposedly limited role of salivary
      venoms in mammalian history. Evidently, small predatory eutherians have
      paralleled colubroid snakes in evolving salivary venoms and their delivery
      systems several times independently.

PMID- 15973407
TI  - Aerodynamics of the hovering hummingbird.
AB  - Despite profound musculoskeletal differences, hummingbirds (Trochilidae) are
      widely thought to employ aerodynamic mechanisms similar to those used by insects.
      The kinematic symmetry of the hummingbird upstroke and downstroke has led to the
      assumption that these halves of the wingbeat cycle contribute equally to weight
      support during hovering, as exhibited by insects of similar size. This assumption
      has been applied, either explicitly or implicitly, in widely used aerodynamic
      models and in a variety of empirical tests. Here we provide measurements of the
      wake of hovering rufous hummingbirds (Selasphorus rufus) obtained with digital
      particle image velocimetry that show force asymmetry: hummingbirds produce 75% of
      their weight support during the downstroke and only 25% during the upstroke. Some
      of this asymmetry is probably due to inversion of their cambered wings during
      upstroke. The wake of hummingbird wings also reveals evidence of leading-edge
      vortices created during the downstroke, indicating that they may operate at
      Reynolds numbers sufficiently low to exploit a key mechanism typical of insect
      hovering. Hummingbird hovering approaches that of insects, yet remains distinct
      because of effects resulting from an inherently dissimilar-avian-body plan.

PMID- 15973408
TI  - Extracellular electron transfer via microbial nanowires.
AB  - Microbes that can transfer electrons to extracellular electron acceptors, such as
      Fe(iii) oxides, are important in organic matter degradation and nutrient cycling
      in soils and sediments. Previous investigations on electron transfer to Fe(iii)
      have focused on the role of outer-membrane c-type cytochromes. However, some
      Fe(iii) reducers lack c-cytochromes. Geobacter species, which are the predominant
      Fe(iii) reducers in many environments, must directly contact Fe(iii) oxides to
      reduce them, and produce monolateral pili that were proposed, on the basis of the
      role of pili in other organisms, to aid in establishing contact with the Fe(iii)
      oxides. Here we report that a pilus-deficient mutant of Geobacter sulfurreducens
      could not reduce Fe(iii) oxides but could attach to them. Conducting-probe atomic
      force microscopy revealed that the pili were highly conductive. These results
      indicate that the pili of G. sulfurreducens might serve as biological nanowires,
      transferring electrons from the cell surface to the surface of Fe(iii) oxides.
      Electron transfer through pili indicates possibilities for other unique cell
      surface and cell-cell interactions, and for bioengineering of novel conductive
      materials.

PMID- 15973409
TI  - Invariant visual representation by single neurons in the human brain.
AB  - It takes a fraction of a second to recognize a person or an object even when seen
      under strikingly different conditions. How such a robust, high-level
      representation is achieved by neurons in the human brain is still unclear. In
      monkeys, neurons in the upper stages of the ventral visual pathway respond to
      complex images such as faces and objects and show some degree of invariance to
      metric properties such as the stimulus size, position and viewing angle. We have
      previously shown that neurons in the human medial temporal lobe (MTL) fire
      selectively to images of faces, animals, objects or scenes. Here we report on a
      remarkable subset of MTL neurons that are selectively activated by strikingly
      different pictures of given individuals, landmarks or objects and in some cases
      even by letter strings with their names. These results suggest an invariant,
      sparse and explicit code, which might be important in the transformation of
      complex visual percepts into long-term and more abstract memories.

PMID- 15973410
TI  - An endocannabinoid mechanism for stress-induced analgesia.
AB  - Acute stress suppresses pain by activating brain pathways that engage opioid or
      non-opioid mechanisms. Here we show that an opioid-independent form of this
      phenomenon, termed stress-induced analgesia, is mediated by the release of
      endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of
      cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain
      prevents non-opioid stress-induced analgesia. In this region, stress elicits the
      rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol
      (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating
      enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and,
      when injected into the periaqueductal grey matter, enhances stress-induced
      analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating
      enzyme fatty-acid amide hydrolase, which selectively elevate anandamide
      concentrations, exert similar effects. Our results indicate that the coordinated
      release of 2-AG and anandamide in the periaqueductal grey matter might mediate
      opioid-independent stress-induced analgesia. These studies also identify
      monoacylglycerol lipase as a previously unrecognized therapeutic target.

PMID- 15973411
TI  - Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function.
AB  - Vertebrate HoxA and HoxD cluster genes are required for proper limb development.
      However, early lethality, compensation and redundancy have made a full assessment
      of their function difficult. Here we describe mice that are lacking all Hoxa and
      Hoxd functions in their forelimbs. We show that such limbs are arrested early in
      their developmental patterning and display severe truncations of distal elements,
      partly owing to the absence of Sonic hedgehog expression. These results indicate
      that the evolutionary recruitment of Hox gene function into growing appendages
      might have been crucial in implementing hedgehog signalling, subsequently leading
      to the distal extension of tetrapod appendages. Accordingly, these mutant limbs
      may be reminiscent of an ancestral trunk extension, related to that proposed for
      arthropods.

PMID- 15973412
TI  - Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect
      against malaria.
AB  - Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin
      chain, protects West African children against Plasmodium falciparum malaria.
      Mechanisms of protection are not established for the heterozygous (haemoglobin
      AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of
      haemoglobin C on the cell-surface properties of P. falciparum-infected
      erythrocytes involved in pathogenesis. Relative to parasite-infected normal
      erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced
      adhesion to endothelial monolayers expressing CD36 and intercellular adhesion
      molecule-1 (ICAM-1). They also show impaired rosetting interactions with non
      parasitized erythrocytes, and reduced agglutination in the presence of pooled
      sera from malaria-immune adults. Abnormal cell-surface display of the main
      variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane
      protein-1), correlates with these findings. The abnormalities in PfEMP-1 display
      are associated with markers of erythrocyte senescence, and are greater in CC than
      in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP
      1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects
      of their sequestration in the microvasculature.

PMID- 15973413
TI  - R gene expression induced by a type-III effector triggers disease resistance in
      rice.
AB  - Disease resistance (R) genes in plants encode products that specifically
      recognise incompatible pathogens and trigger a cascade of events leading to
      disease resistance in the host plant. R-gene specificity is dictated by both host
      R genes and cognate avirulence (avr) genes in pathogens. However, the basis of
      gene-for-gene specificity is not well understood. Here, we report the cloning of
      the R gene Xa27 from rice and the cognate avr gene avrXa27 from Xanthomonas
      oryzae pv. oryzae. Resistant and susceptible alleles of Xa27 encode identical
      proteins. However, expression of only the resistant allele occurs when a rice
      plant is challenged by bacteria harbouring avrXa27, whose product is a nuclear
      localized type-III effector. Induction of Xa27 occurs only in the immediate
      vicinity of infected tissue, whereas ectopic expression of Xa27 resulted in
      resistance to otherwise compatible strains of the pathogen. Thus Xa27 specificity
      towards incompatible pathogens involves the differential expression of the R gene
      in the presence of the AvrXa27 effector.

PMID- 15973414
TI  - EphB receptor activity suppresses colorectal cancer progression.
AB  - Most sporadic colorectal cancers are initiated by activating Wnt pathway
      mutations, characterized by the stabilization of beta-catenin and constitutive
      transcription by the beta-catenin/T cell factor-4 (Tcf-4) complex. EphB guidance
      receptors are Tcf4 target genes that control intestinal epithelial architecture
      through repulsive interactions with Ephrin-B ligands. Here we show that, although
      Wnt signalling remains constitutively active, most human colorectal cancers lose
      expression of EphB at the adenoma-carcinoma transition. Loss of EphB expression
      strongly correlates with degree of malignancy. Furthermore, reduction of EphB
      activity accelerates tumorigenesis in the colon and rectum of Apc(Min/+) mice,
      and results in the formation of aggressive adenocarcinomas. Our data demonstrate
      that loss of EphB expression represents a critical step in colorectal cancer
      progression.

PMID- 15973416
TI  - EGFP as your targeted 'hitman'.

PMID- 15973417
TI  - Tissue microarrays without cores.

PMID- 15973418
TI  - Tag-based approaches for transcriptome research and genome annotation.
AB  - With the increasing number of whole genome sequences available, genomic research
      has shifted toward the annotation of functional elements and transcribed regions.
      Thus, the related field of transcriptome research requires accurate methods for
      the profiling of genes that are not biased by known sequence information, and
      that also allow for the identification of promoter regions. Starting with serial
      analysis of gene expression (SAGE), methods making use of short sequencing tags
      have greatly contributed to transcriptome studies. Here we review recent
      developments in the use of short sequencing tags in expression profiling, gene
      discovery and genome annotation. These tags are obtained from the 5' end of
      mRNAs, both terminal ends of mRNAs, or genomic regions. The 5' end-specific tags,
      with their ability to identify transcripts along with their transcriptional start
      sites, will be of particular interest for gene network studies and may become one
      of the most important approaches in systems biology.

PMID- 15973419
TI  - Multiphoton excitation-evoked chromophore-assisted laser inactivation using green
      fluorescent protein.
AB  - Noninvasive, straightforward methods to inactivate selected proteins in living
      cells with high spatiotemporal resolution are needed. Chromophore-assisted laser
      inactivation (CALI) can be used to photochemically inactivate proteins, but it
      has several drawbacks, such as procedural complexity and nonspecific photodamage.
      Here we show that by application of multiphoton excitation to CALI, enhanced
      green fluorescent protein (EGFP) is an effective chromophore for inactivation of
      a protein's function without nonspecific photodamage in living mammalian cells.

PMID- 15973420
TI  - Colony filtration blot: a new screening method for soluble protein expression in
      Escherichia coli.
AB  - The implementation of efficient technologies for the production of recombinant
      mammalian proteins remains an outstanding challenge in many structural and
      functional genomics programs. We have developed a new method for rapid
      identification of soluble protein expression in E. coli, based on a separation of
      soluble protein from inclusion bodies by a filtration step at the colony level.
      The colony filtration (CoFi) blot is very well suited to screen libraries, and in
      the present work we used it to screen a deletion mutagenesis library.

PMID- 15973421
TI  - Ultrahigh density microarrays of solid samples.
AB  - We present a sectioning and bonding technology to make ultrahigh density
      microarrays of solid samples, cutting edge matrix assembly (CEMA). Maximized
      array density is achieved by a scaffold-free, self-supporting construction with
      rectangular array features that are incrementally scalable. This platform
      technology facilitates arrays of >10,000 tissue features on a standard glass
      slide, inclusion of unique sample identifiers for improved manual or automated
      tracking, and oriented arraying of stratified or polarized samples.

PMID- 15973422
TI  - Nanoscale mapping and functional analysis of individual adhesins on living
      bacteria.
AB  - Although much progress has been made in the identification and characterization
      of adhesins borne by pathogenic bacteria, the molecular details underlying their
      interaction with host receptors remain largely unknown owing to the lack of
      appropriate probing techniques. Here we report a method, based on atomic force
      microscopy (AFM) with tips bearing biologically active molecules, for measuring
      the specific binding forces of individual adhesins and for mapping their
      distribution on the surface of living bacteria. First, we determined the adhesion
      forces between the heparin-binding haemagglutinin adhesin (HBHA) produced by
      Mycobacterium tuberculosis and heparin, used as a model sulphated glycoconjugate
      receptor. Both the adhesion frequency and adhesion force increased with contact
      time, indicating that the HBHA-heparin complex is formed via multiple
      intermolecular bridges. We then mapped the distribution of single HBHA molecules
      on the surface of living mycobacteria and found that the adhesin is not randomly
      distributed over the mycobacterial surface, but concentrated into nanodomains.

PMID- 15973423
TI  - Enzymatic detection of protein translocation.
AB  - Fundamental to eukaryotic cell signaling is the regulation of protein function by
      directed localization. Detection of these events has been largely qualitative
      owing to the limitations of existing technologies. Here we describe a method for
      quantitatively assessing protein translocation using proximity-induced enzyme
      complementation. The complementation assay for protein translocation (CAPT) is
      derived from beta-galactosidase and comprises one enzyme fragment, omega, which
      is localized to a particular subcellular region, and a small complementing
      peptide, alpha, which is fused to the protein of interest. The concentration of
      alpha in the immediate vicinity of omega correlates with the amount of enzyme
      activity obtained in a dose- and time-dependent manner, thus acting as a
      genetically encoded biosensor for local protein concentration. Using CAPT,
      inducible protein movement from the cytosol to the nucleus or plasma membrane was
      quantitatively monitored in multiwell format and in live mammalian cells by flow
      cytometry.

PMID- 15973431
TI  - POT1 protects telomeres from a transient DNA damage response and determines how
      human chromosomes end.
AB  - The hallmarks of telomere dysfunction in mammals are reduced telomeric 3'
      overhangs, telomere fusions, and cell cycle arrest due to a DNA damage response.
      Here, we report on the phenotypes of RNAi-mediated inhibition of POT1, the single
      stranded telomeric DNA-binding protein. A 10-fold reduction in POT1 protein in
      tumor cells induced neither telomere fusions nor cell cycle arrest. However, the
      3' overhang DNA was reduced and all telomeres elicited a transient DNA damage
      response in G1, indicating that extensive telomere damage can occur without cell
      cycle arrest or telomere fusions. RNAi to POT1 also revealed its role in
      generating the correct sequence at chromosome ends. The recessed 5' end of the
      telomere, which normally ends on the sequence ATC-5', was changed to a random
      position within the AATCCC repeat. Thus, POT1 determines the structure of the 3'
      and 5' ends of human chromosomes, and its inhibition generates a novel
      combination of telomere dysfunction phenotypes in which chromosome ends behave
      transiently as sites of DNA damage, yet remain protected from nonhomologous end
      joining.

PMID- 15973432
TI  - Structure and function of the complex formed by the tuberculosis virulence
      factors CFP-10 and ESAT-6.
AB  - The secreted Mycobacterium tuberculosis complex proteins CFP-10 and ESAT-6 have
      recently been shown to play an essential role in tuberculosis pathogenesis. We
      have determined the solution structure of the tight, 1:1 complex formed by CFP-10
      and ESAT-6, and employed fluorescence microscopy to demonstrate specific binding
      of the complex to the surface of macrophage and monocyte cells. A striking
      feature of the complex is the long flexible arm formed by the C-terminus of CFP
      10, which was found to be essential for binding to the surface of cells. The
      surface features of the CFP-10.ESAT-6 complex, together with observed binding to
      specific host cells, strongly suggest a key signalling role for the complex, in
      which binding to cell surface receptors leads to modulation of host cell
      behaviour to the advantage of the pathogen.

PMID- 15973433
TI  - The protein translocation channel binds proteasomes to the endoplasmic reticulum
      membrane.
AB  - Misfolded secretory proteins are transported across the endoplasmic reticulum
      (ER) membrane into the cytosol for degradation by proteasomes. A large fraction
      of proteasomes in a cell is associated with the ER membrane. We show here that
      binding of proteasomes to ER membranes is salt sensitive, ATP dependent, and
      mediated by the 19S regulatory particle. The base of the 19S particle, which
      contains six AAA-ATPases, binds to microsomal membranes with high affinity,
      whereas the 19S lid complex binds weakly. We demonstrate that ribosomes and
      proteasomes compete for binding to the ER membrane and have similar affinities
      for their receptor. Ribosomes bind to the protein conducting channel formed by
      the Sec61 complex in the ER membrane. We co-precipitated subunits of the Sec61
      complex with ER-associated proteasome 19S particles, and found that
      proteoliposomes containing only the Sec61 complex retained proteasome binding
      activity. Collectively, our data suggest that the Sec61 channel is a principal
      proteasome receptor in the ER membrane.

PMID- 15973434
TI  - Transmembrane topogenesis of a tail-anchored protein is modulated by membrane
      lipid composition.
AB  - A large class of proteins with cytosolic functional domains is anchored to
      selected intracellular membranes by a single hydrophobic segment close to the C
      terminus. Although such tail-anchored (TA) proteins are numerous, diverse, and
      functionally important, the mechanism of their transmembrane insertion and the
      basis of their membrane selectivity remain unclear. To address this problem, we
      have developed a highly specific, sensitive, and quantitative in vitro assay for
      the proper membrane-spanning topology of a model TA protein, cytochrome b5 (b5).
      Selective depletion from membranes of components involved in cotranslational
      protein translocation had no effect on either the efficiency or topology of b5
      insertion. Indeed, the kinetics of transmembrane insertion into protein-free
      phospholipid vesicles was the same as for native ER microsomes. Remarkably,
      loading of either liposomes or microsomes with cholesterol to levels found in
      other membranes of the secretory pathway sharply and reversibly inhibited b5
      transmembrane insertion. These results identify the minimal requirements for
      transmembrane topogenesis of a TA protein and suggest that selectivity among
      various intracellular compartments can be imparted by differences in their lipid
      composition.

PMID- 15973435
TI  - Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP.
AB  - SHP (small heterodimer partner) is an important component of the feedback
      regulatory cascade, which controls the conversion of cholesterol to bile acids.
      In order to identify the bona fide molecular targets of SHP, we performed global
      gene expression profiling combined with chromatin immunoprecipitation assays in
      transgenic mice constitutively expressing SHP in the liver. We demonstrate that
      SHP affects genes involved in diverse biological pathways, and in particular,
      several key genes involved in consecutive steps of cholesterol degradation, bile
      acid conjugation, transport and lipogenic pathways. Sustained expression of SHP
      leads to the depletion of hepatic bile acid pool and a concomitant accumulation
      of triglycerides in the liver. The mechanism responsible for this phenotype
      includes SHP-mediated direct repression of downstream target genes and the bile
      acid sensor FXRalpha, and an indirect activation of PPARgamma and SREBP-1c genes.
      We present evidence for the role of altered chromatin configurations in defining
      distinct gene-specific mechanisms by which SHP mediates differential
      transcriptional repression. The multiplicity of genes under its control suggests
      that SHP is a pleiotropic regulator of diverse metabolic pathways.

PMID- 15973436
TI  - Eyg and Ey Pax proteins act by distinct transcriptional mechanisms in Drosophila
      development.
AB  - Drosophila has two pairs of Pax genes, ey/toy and eyg/toe, that play different
      functions during eye development. ey specifies eye fate, while eyg promotes cell
      proliferation. We have determined the molecular basis for the functional
      diversity of Eyg and Ey. Eyg and Ey act by distinct transcriptional mechanisms.
      They use different DNA-binding domains for target recognition. Most
      interestingly, Eyg acts exclusively as a repressor, whereas Ey is an activator.
      Several vertebrate Pax proteins are known to switch between activator and
      repressor activities, but none as repressors only. Eyg may be the first Pax
      protein as a dedicated repressor. Vertebrates produce a Pax6 isoform, Pax6-5a,
      differing from Pax6 in DNA-binding properties and functions and structurally
      similar to Eyg/Toe. We found that Pax6-5a acts as an activator like Ey, but has
      DNA-binding specificity like Eyg.

PMID- 15973437
TI  - Swf1-dependent palmitoylation of the SNARE Tlg1 prevents its ubiquitination and
      degradation.
AB  - Protein palmitoylation is a post-translational modification that affects a great
      number of proteins. In most cases, the enzymes responsible for this modification
      have not been identified. Some proteins use palmitoylation to attach themselves
      to membranes; however, palmitoylation also occurs in transmembrane proteins, and
      the function of this palmitoylation is less clear. Here we identify Swf1, a
      member of the DHHC-CDR family of palmitoyltransferases, as the protein
      responsible for modifying the yeast SNAREs Snc1, Syn8 and Tlg1, at cysteine
      residues close to the cytoplasmic end of their single transmembrane domains
      (TMDs). In an swf1Delta mutant, Tlg1 is mis-sorted to the vacuole. This occurs
      because unpalmitoylated Tlg1 is recognised by the ubiquitin ligase Tul1,
      resulting in its targeting to the multivesicular body pathway. Our results
      suggest that one role of palmitoylation is to protect TMDs from the cellular
      quality control machinery, and that Swf1 may be the enzyme responsible for most,
      if not all, TMD-associated palmitoylation in yeast.

PMID- 15973438
TI  - Bacterial transfer of large functional genomic DNA into human cells.
AB  - Efficient transfer of chromosome-based vectors into mammalian cells is difficult,
      mostly due to their large size. Using a genetically engineered invasive
      Escherichia coli vector, alpha satellite DNA cloned in P1-based artificial
      chromosome was stably delivered into the HT1080 cell line and efficiently
      generated human artificial chromosomes de novo. Similarly, a large genomic cystic
      fibrosis transmembrane conductance regulator (CFTR) construct of 160 kb
      containing a portion of the CFTR gene was stably propagated in the bacterial
      vector and transferred into HT1080 cells where it was transcribed, and correctly
      spliced, indicating transfer of an intact and functional locus of at least 80 kb.
      These results demonstrate that bacteria allow the cloning, propagation and
      transfer of large intact and functional genomic DNA fragments and their
      subsequent direct delivery into cells for functional analysis. Such an approach
      opens new perspectives for gene therapy.

PMID- 15973440
TI  - Gene therapy progress and prospects: stem cell plasticity.
AB  - With the identification of stem cell plasticity several years ago, multiple
      reports raised hopes that tissue repair by stem cell transplantation could be
      within reach in the near future. Krause et al reported that a single purified
      hematopoietic stem cell not only repopulated the bone marrow of a host animal,
      but also integrated into unrelated tissues. Lagasse et al demonstrated that in a
      genetic model of liver disease, purified hematopoietic stem cells can give rise
      to hepatocytes and rescue fatal liver damage. More recent work by Jiang et al
      demonstrated that cultured cells can retain their stem cell potential. There are
      a number of possible mechanisms that could explain these phenomena, and recent
      experiments have raised controversy about which mechanism is prevalent. One
      possibility is transdifferentiation of a committed cell directly into another
      cell type as a response to environmental cues. Transdifferentiation has been
      shown mainly in vitro, but some in vivo data also support this mechanism. Direct
      transdifferentiation would clinically be limited by the number of cells that can
      be introduced into an organ without removal of resident cells. If bone marrow
      cells could on the other hand give rise to stem cells of another tissue, then
      they could in theory repopulate whole organs from a few starting cells. This
      model of dedifferentiation is consistent with recent data from animal models.
      Genetic analysis of cells of donor origin in vivo and in vitro has brought to
      light another possible mechanism. The fusion of host and donor cells can give
      rise to mature tissue cells without trans- or dedifferentiation. The resulting
      heterokaryons are able to cure a lethal genetic defect and do not seem to be
      prone to give rise to cancer. All these models will clinically face the problem
      of accessibility of healthy primary cells for transplantation. This underlines
      the importance of the recent identification of a population of mesenchymal stem
      cells (MSCs) with stem cell properties similar to embryonic stem (ES) cells.
      These cells can be cultured and expanded in vitro without losing their stem cell
      potential making them an attractive target for cell therapy. Finally, it is still
      not clear if stem cells for various tissues are present in peripheral blood, or
      bone marrow and thus can be directly purified from these sources. Identification
      of putative tissue stem cells would be necessary before purification strategies
      can be devised. In this review, we discuss the evidence for these models, and the
      conflicting results obtained to date.

PMID- 15973441
TI  - Direct electrotransfer of hHGF gene into kidney ameliorates ischemic acute renal
      failure.
AB  - In the early phase of kidney transplantation, the transplanted kidney is exposed
      to insults like ischemia/reperfusion, which is a leading cause of acute renal
      failure (ARF). ARF in the context of renal transplantation predisposes the graft
      to developing chronic damage and to long-term graft loss. Hepatocyte growth
      factor (HGF) has been suggested to support the intrinsic ability of the kidney to
      regenerate in response to injury by its morphogenic, mitogenic, motogenic and
      antiapoptotic activities. In the present paper, we examine whether human HGF
      (hHGF) gene electrotransfer helps in the recovery from ARF in a model of rat
      renal warm ischemia. We also assess the advantages of this form of gene therapy
      by direct electroporation of the kidney, given that transplantation offers the
      possibility of manipulating the organ in vivo. We have compared the therapeutic
      efficiency of two electroporation methodologies in a rat ARF model. Although they
      both targeted the same organ, the two methods were applied to different parts of
      the animal: muscle and kidney. Kidney direct electrotransfer was shown to be more
      efficient not only in pharmacokinetic but also in therapeutic terms, so it may
      become a clinically practical alternative in renal transplantation.

PMID- 15973442
TI  - Transient cutaneous adenoviral gene therapy with human host defense peptide hCAP
      18/LL-37 is effective for the treatment of burn wound infections.
AB  - Host defense peptides (HDP) are naturally occurring effector molecules of the
      innate immune system, which might be an alternative to currently used
      antibiotics. The objective of this study was to investigate the efficiency of
      transient cutaneous adenoviral transfection with human cathelicidin hCAP-18/LL-37
      in infected burn wounds. Specific transgene expression was analyzed in vitro on
      mRNA and protein level using real-time PCR and Western-blot. Male Sprague-Dawley
      rats (n=40) received a second degree scald burn on both flanks (5% BSA), which
      were inoculated with 10(8) colony-forming units (CFU) Pseudomonas aeruginosa. Two
      days later, rats were randomized into the following groups: (1) adenoviral
      delivery of LL-37 (Ad5-hCAP-18, n=10), (2) synthetic host defense peptide LL-37
      (1 mg; n=10), (3) carrier control (PBS, n=10) and (4) empty-virus control (Ad5
      LacZ, n=10). Agents were injected intradermally and subcutaneously into both
      flanks. After either 2 or 7 days, skin samples were harvested and homogenized.
      CFU per gram tissue were determined. The hCAP-18/LL-37 expression was confirmed
      by real-time PCR and localized using in situ hybridization. In vitro transfection
      of cutaneous cells delivered a specific response on mRNA production. Western blot
      analysis revealed protein expression of hCAP-18/LL-37 in conditioned medium and
      cell pellet. The host defense peptide LL-37 was detectable after cleavage of the
      inactive pro-form hCAP-18/LL-37 with human elastase. Ad5-hCAP-18 showed a
      significant bacterial inhibition of approximately 10 000 fold compared to the
      control group (P<0.001) and 1000-fold (P<0.001) compared to the synthetic HDP LL
      37 7 post-transfection. No inhibition was observed for the carrier or empty-virus
      control. Real-time PCR and in situ hybridization confirmed expression of hCAP
      18/LL-37. In conclusion, transient cutaneous adenoviral delivery of the host
      defense peptide hCAP-18/LL-37 is significantly more effective than administration
      of synthetic host defense peptides and might be a potential adjunct for wound
      treatment in the near future.

PMID- 15973443
TI  - In vitro-generated regulatory T cells induced by Foxp3-retrovirus infection
      control murine contact allergy and systemic autoimmunity.
AB  - Regulatory T cells are promising candidates for the modulation of inflammation
      and autoimmunity. To generate regulatory T cells in vitro, we have infected naive
      CD4+CD25- T cells with a retrovirus encoding the transcription factor Foxp3.
      Foxp3-infected T cells are similar to naturally occurring regulatory T cells as
      evidenced by surface marker expression and function. To investigate the effects
      of Foxp3-infected T cells on contact hypersensitivity (CHS) responses, sensitized
      mice were injected with Foxp3- or control virus-infected T cells. Only injection
      of Foxp3-infected T cells into sensitized mice significantly inhibited CHS
      compared to controls, indicating that Foxp3-infected T cells are suppressive in
      vivo. These findings prompted treatment of autoimmune-prone CD40L transgenic (tg)
      mice, which develop a severe systemic autoimmune disease including autoreactive T
      cells and autoantibodies, with Foxp3-infected T cells. Interestingly, injections
      of Foxp3-infected T cells into CD40L tg mice inhibited the ongoing development of
      autoimmune dermatitis and activation of cytotoxic CD8+ T cells. Strikingly,
      treatment with Foxp3-infected T cells reduced serum concentrations of antinuclear
      antibodies in CD40L tg mice, which was paralleled with reduced renal
      immunoglobulin depositions and increased kidney function. Together, these
      findings indicate that newly in vitro-generated regulatory T cells can be
      successfully used to treat inflammatory and ongoing autoimmune disorders.

PMID- 15973444
TI  - Normal growth and regenerating ability of myoblasts from unaffected muscles of
      facioscapulohumeral muscular dystrophy patients.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease
      characterized by a typical regional distribution, featuring composed patterns of
      clinically affected and unaffected muscles. No treatment is available for this
      condition, in which the pathophysiological mechanism is still unknown. Autologous
      transfer of myoblasts from unaffected to affected territories could be considered
      as a potential strategy to delay or stop muscle degeneration. To evaluate the
      feasibility of this concept, we explored and compared the growth and
      differentiation characteristics of myoblasts prepared from phenotypically
      unaffected muscles of five FSHD patients and 10 control donors. According to a
      clinically approved procedure, 10(9) cells of a high degree of purity were
      obtained within 16-23 days. More than 80% of these cells were myoblasts, as
      demonstrated by labeling of the muscle markers CD56 and desmin. FSHD myoblasts
      presented a doubling time equivalent to that of control cells; they kept high
      proliferation ability and did not show early telomere shortening. In vitro, these
      cells were able to differentiate and to express muscle-specific antigens. In
      vivo, they participated to muscle structures when injected into immunodeficient
      mice. These data suggest that myoblasts expanded from unaffected FSHD muscles may
      be suitable tools in view of autologous cell transplantation clinical trials.

PMID- 15973445
TI  - The systemic administration of Ig-4-1BB ligand in combination with IL-12 gene
      transfer eradicates hepatic colon carcinoma.
AB  - We have previously shown that the local-membrane bound 4-1BB ligand and IL-12
      gene transfer induced a significant antitumor response in a mouse colon carcinoma
      model. However, a high viral dose was required in order to achieve the best
      efficacy. In this study, we hypothesize that the systemic administration of
      soluble Ig-4-1BB ligand can give rise to better T-cell immune activation than
      local gene delivery. With potential clinical applications in mind, we further
      compare whether the natural 4-1BB ligand fused to mouse IgG2a (Ig-4-1BBL) would
      be as effective as the agonistic anti-4-1BB antibody. The dimeric form of Ig-4
      1BBL was purified from HeLa cells transduced with a recombinant adenovirus
      (ADV/Ig-4-1BBL) expressing Ig-4-1BBL. Functional activity was confirmed by the
      ligand's ability to bind to activated splenic T cells or bone marrow (BM)-derived
      dendritic cells (DCs) that express 4-1BB receptor. The soluble Ig-4-1BBL
      efficiently costimulated CD3-activated T-cell proliferation in vitro. More
      importantly, it induced tumor-specific CTLs as effectively as the agonistic anti
      4-1BB antibody. When combined with IL-12 gene transfer, systemic administration
      of the Ig-4-1BBL proved to be more potent than local gene delivery. In addition,
      the Ig-4-1BBL is as potent as the agonistic anti-4-1BB antibody for the treatment
      of hepatic MCA26 colon carcinoma, resulting in 50% complete tumor regression and
      long-term survival. In long-term surviving mice, both treatment modalities
      induced persistent tumor-specific CTL activity. In summary, these results suggest
      that the systemic delivery of Ig-4-1BBL can generate a better antitumor response
      than local gene delivery. Ig-4-1BBL had equivalent biological functions when
      compared to the agonistic anti-4-1BB antibody. Thus, soluble 4-1BBL dimmer can be
      developed as a promising agent for cancer therapy in humans.

PMID- 15973447
TI  - Therapeutic renaissance of thalidomide in the treatment of haematological
      malignancies.
AB  - Very few drugs had a history similar to that of thalidomide (alpha-N
      [phthalimido] gluramide). First introduced in the late 1950s in Germany, in 1961
      thalidomide was withdrawn due to its teratogenic effects. More than three decades
      after, it is attracting growing interest because of its reported immunomodulatory
      and anti-inflammatory properties. The discovery that thalidomide inhibits
      angiogenesis led to preclinical and clinical trials as an anticancer agent in the
      treatment of solid tumours and haematological malignancies, as summarized in this
      review article. More recently, structural analogues of thalidomide have been
      synthesized in order to explore potential molecular targets of thalidomide, as
      well as to identify new agents with improved therapeutic efficacy.

PMID- 15973446
TI  - Discrimination of biclonal B-cell chronic lymphoproliferative neoplasias by
      tetraspanin antigen expression.

PMID- 15973448
TI  - Acute lymphoblastic leukemia in a patient with congenital neutropenia without G
      CSF-R and ELA2 mutations.

PMID- 15973449
TI  - Theoretical basis for maintenance therapy of childhood ALL.

PMID- 15973450
TI  - Molecular heterogeneity of sporadic adult Burkitt-type leukemia/lymphoma as
      revealed by PCR and cytogenetics: correlation with morphology, immunology and
      clinical features.
AB  - Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt
      lymphoma but they are only found in a varying frequency in mature Burkitt-type
      acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic
      Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32),
      t(2;8)(p11;q24) and t(8;22)(q24;q11). Long PCR was used for detecting the
      immunoglobulin heavy chain (IgH) translocation and cytogenetics and/or
      fluorescence in situ hybridization for detecting the 'variant' MYC
      translocations. A total of 29 samples (51.8%) were t(8;14)-positive by long PCR.
      Approximately one-third had a chromosomal breakpoint in the IgH joining region
      while the others had breakpoints in the IgH switch regions. Among them were two
      cases with a previously unreported MYC translocation into the IgE switch region.
      Long PCR was more reliable compared to conventional cytogenetics for detecting
      the t(8;14). Epstein-Barr virus was detected in high copy number in two (3.6%)
      t(8;14)-positive cases by real-time quantitative PCR. Human herpesvirus 8 was not
      detected in any case by nested PCR. A typical L3 or L3-compatible cytomorphology
      was highly predictive (>80%) but not specific of a MYC translocation. A total of
      34 patients were treated according to the GMALL B-ALL therapy protocols and there
      was no significant difference in overall survival between patients with or
      without t(8;14).

PMID- 15973451
TI  - Simultaneous detection of NPM1 and FLT3-ITD mutations by capillary
      electrophoresis in acute myeloid leukemia.
AB  - Mutations in the Nucleophosmin (NPM1) gene have been recently described to occur
      in about one-third of acute myeloid leukemias (AML) and represent the most
      frequent genetic alteration currently known in this subset. These mutations
      generate an elongated NPM1 protein that localizes aberrantly in the cytoplasm. In
      analogy with Flt3 alterations, NPM1 mutations are mostly detectable in AML with
      normal karyotype and their recognition may be relevant to identify distinct
      response to treatment. Hence, in addition to conventional karyotyping and RT-PCR
      of fusion genes, combined analysis of both Flt3 and NPM1 mutations will be
      increasingly relevant in the genetic diagnosis work-up of AML. We developed a
      multiplex RT-PCR assay followed by capillary electrophoresis to simultaneously
      analyze NPM1 and Flt3 gene alterations (NFmPCR assay). The assay was validated in
      leukemic cell RNAs extracted from 38 AML patients, which had been previously
      characterized for Flt3 status by conventional RT-PCR. Direct sequencing of NPM1
      RT-PCR products was carried out in 15 cases to verify results obtained by
      capillary electrophoresis. Both NPM1 sequencing and conventional RT-PCR Flt3
      results showed 100% concordance with the results of the NFmPCR assay. We suggest
      that this assay may be introduced in routine analysis of genetic alterations in
      AML.

PMID- 15973452
TI  - Comparative analysis of the effects of sample source and test methodology on the
      assessment of protein expression in acute myelogenous leukemia.
AB  - Numerous studies have analyzed the expression and prognostic importance of
      various proteins in acute myelogenous leukemia (AML). We sought to determine
      whether the sample source and methodology used to measure protein expression
      affect the results obtained. To determine the importance of sample source, we
      used Western blotting to compare the expression of eight proteins and
      phosphoproteins in the leukemia blast-enriched fraction of 118 blood- and 108
      marrow-derived samples, including 37 paired samples. To determine the importance
      of methodology, the expression of five proteins was measured in 20 paired samples
      by Western blotting, laser scanning cytometry (LSC), and flow cytometry. The mean
      expression and range of expression in blood- and marrow-derived samples were
      statistically identical for all eight proteins. Expression measurements for the
      37 paired blood and marrow samples also had very high statistical correlation.
      The LSC and flow cytometry data had the highest concordance when compared using
      Kolmogorov-Smirnoff D-stats (range of R values, 0.8-1.0). High concordance was
      also observed between the LSC and flow cytometry results when the percentage of
      cells positive for expression was dichotomized into positive or negative
      expression. However, there was less correlation between LSC and flow cytometry
      when the actual percentages of positive cells were compared. The majority of
      discordant situations involved samples that were positive by flow cytometry but
      negative by LSC. The correlation between Western blotting signal intensity and
      the percentage of expression-positive cells measured by LSC or flow cytometry
      varied by protein but was limited when there was little heterogeneity in
      expression by either method. In conclusion, provided that leukemia blast-enriched
      fractions were analyzed, the blood- and marrow-derived samples had identical
      protein expression. There was good concordance of results between flow cytometry
      and LSC, which share similar technology, but more limited correlation between
      these methods and Western blotting.

PMID- 15973453
TI  - Clonal selection in the bone marrow involvement of follicular lymphoma.
AB  - To characterize the pathways of bone marrow (BM) involvement of follicular
      lymphoma (FL), we performed morphological and immunophenotypical analysis of
      tumor cells from lymph nodes (LNs) and corresponding BMs in 21 patients with FL.
      In three cases, genealogical trees were constructed based on the immunoglobulin
      variable region heavy chain (IgV(H)) gene sequences of tumor clones from LNs and
      BMs. Results showed that FLs within the BMs display identical or lower
      cytological grades than in the LNs. In the majority of cases, different
      proportions of tumor cells expressed bcl-2, CD10 and Ki67 in LNs and BMs. Tumor
      cells in the BM showed ongoing somatic hypermutation of the IgV(H) genes; the
      distribution of these mutations was highly consistent with antigen selection. The
      topology of the genealogical trees revealed that different subclones populate the
      LN and BM and BM infiltration may occur at different points of the clonal
      evolution of FL. Early descendants of the original tumor clone and derivatives of
      diversified tumor clones may invade the BM. These results suggest that the BM
      involvement of FL is associated with intensive clonal selection of tumor cells,
      and the BM provides a microenvironment similar to the germinal centers of LNs,
      where tumor cells retain their biological nature.

PMID- 15973454
TI  - Overt testicular disease at diagnosis of childhood acute lymphoblastic leukemia:
      lack of therapeutic role of local irradiation.
AB  - To assess the prognosis of overt testicular disease at diagnosis of acute
      lymphoblastic leukemia, and any therapeutic role of irradiation for this
      involvement, we reviewed the data of 811 boys treated on St Jude studies Total X-
      XI (early period) and Total XII-XIV (recent period). In all, 19 boys (2.3%) had
      testicular disease at diagnosis. In the early period, patients with testicular
      leukemia had a poorer overall survival (OS) (P=0.003), event-free survival (EFS)
      (P=0.064), and higher cumulative incidence of relapse (P=0.041) than did other
      patients. During the recent period, patients with and without overt testicular
      leukemia did not differ in OS (P=0.257), EFS (P=0.102), or cumulative incidence
      of relapse (P=0.51). In a multivariate analysis, OS was lower for patients with
      testicular disease than for those without the involvement in the early period
      (P=0.047) but not in the recent one (P=0.75). Both patients who received
      irradiation for residual testicular disease at the end of induction subsequently
      died of leukemia. Of the other 17 patients who did not receive irradiation, only
      one developed testicular relapse in combination with bone marrow relapse. In
      conclusion, the prognostic impact of overt testicular disease has diminished.
      Irradiation appears to provide no survival advantage to this patient population.

PMID- 15973455
TI  - Insights into the multistep transformation process of lymphomas: IgH-associated
      translocations and tumor suppressor gene mutations in clonally related composite
      Hodgkin's and non-Hodgkin's lymphomas.
AB  - Clonally related composite lymphomas of Hodgkin's lymphoma (HL) and Non-Hodgkin's
      lymphoma (NHL) represent models to study the multistep transformation process in
      tumorigenesis and the development of two distinct tumors from a shared precursor.
      We analyzed six such lymphomas for transforming events. The HLs were combined in
      two cases with follicular lymphoma (FL), and in one case each with B-cell chronic
      lymphocytic leukemia, splenic marginal zone lymphoma, mantle cell lymphoma (MCL)
      and diffuse large B-cell lymphoma (DLBCL). In the HL/FL and HL/MCL combinations,
      BCL2/IGH and CCND1/IGH translocations, respectively, were detected in both the HL
      and NHL. No mutations were found in the tumor suppressor genes FAS, NFKBIA and
      ATM. The HL/DLBCL case harbored clonal replacement mutations of the TP53 gene on
      both alleles exclusively in the DLBCL. In conclusion, we present the first
      examples of molecularly verified IgH-associated translocations in HL, which also
      show that BCL2/IGH or CCND1/IGH translocations can represent early steps in the
      pathogenesis of composite HL/FL or HL/MCL. The restriction of the TP53 mutations
      to the DLBCL in the HL/DLBCL case exemplifies a late transforming event that
      presumably happened in the germinal center and affected the fate of a common
      lymphoma precursor cell towards development of a DLBCL.

PMID- 15973456
TI  - A defined donor activating natural killer cell receptor genotype protects against
      leukemic relapse after related HLA-identical hematopoietic stem cell
      transplantation.
AB  - Killer cell immunoglobulin-like receptors (KIRs) recognize different groups of
      Human Leukocyte Antigen (HLA) class I alleles and are expressed by natural killer
      (NK) cells and some T lymphocytes. NK cell cytotoxicity is triggered by failure
      to recognize the appropriate HLA class I ligand on target cells. Recently, it has
      been shown that HLA class I ligand incompatibility in the graft-versus-host (GvH)
      direction is associated with a better outcome in haploidentical hematopoietic
      stem cell transplantation (HSCT). Since KIR genotypes are very diverse in the
      population, we explored whether or not the donor KIR genotype could affect the
      graft-versus-leukemia (GvL) effect in the related HLA-identical HSCT setting. We
      determined the KIR and HLA genotypes of 65 HLA-identical patient-donor siblings.
      We found that the presence of two activating KIRs, 2DS1 and 2DS2, in the donor
      was significantly associated with a decreased leukemic relapse rate (P=0.03;
      OR=0.18; 95% CI: 0.037-0.88). Moreover, the probability of relapse at 5 years was
      significantly lower for patients who received a graft from a donor with the
      2DS1(+)2DS2(+) genotype than for those who received a transplant from other
      donors (17 vs 63%, respectively; P=0.018). In conclusion, this study suggests
      that a joint effect of these two selected activating KIRs in the donor might
      confer some protection against leukemic relapse.

PMID- 15973457
TI  - DEK-CAN molecular monitoring of myeloid malignancies could aid therapeutic
      stratification.
AB  - The t(6;9)(p23;q34) is a recurrent chromosomal abnormality observed in 1% of
      acute myelogenous leukemia (AML), which generates a fusion transcript between DEK
      and CAN/NUP214 genes. We used a DEK-CAN real-time quantitative (RQ)-PCR strategy
      to analyze 79 retrospective and prospective samples from 12 patients. Five
      patients reached DEK-CAN negativity (sensitivity 10(-5)); all underwent early
      allogeneic hematopoietic stem cell transplantation (median 5.5 months from
      diagnosis) with some demonstrating molecular positivity at the time of allograft.
      All four cases in CCR with adequate follow-up (median 18.5 months, range 13--95)
      demonstrate persistent molecular negativity, whereas all seven patients with
      persistent DEK-CAN positivity died at a median of 12 months from diagnosis (range
      7--27). We conclude that DEK-CAN molecular monitoring by RQ-PCR in t(6;9)
      malignancies is a useful tool for individual patient management and that
      molecular negativity is indispensable for survival, but should not be a
      prerequisite for allografting in this rare, poor prognosis, subset of AML.

PMID- 15973458
TI  - An amino-acid switch in the BCR-ABL kinase domain modifies sensitivity to
      imatinib mesylate.

PMID- 15973459
TI  - Multiple sclerosis genetics: leaving no stone unturned.
AB  - Compelling epidemiologic and molecular data indicate that genes play a primary
      role in determining who is at risk for developing multiple sclerosis (MS), how
      the disease progresses, and how someone responds to therapy. The genetic
      component of MS etiology is believed to result from the action of allelic
      variants in several genes. Their incomplete penetrance and moderate individual
      effect probably reflects epistatic interactions, post-transcriptional regulatory
      mechanisms, and significant environmental influences. Equally significant, it is
      also likely that locus heterogeneity exists, whereby specific genes influence
      susceptibility and pathogenesis in some individuals but not in others. With the
      aid of novel analytical algorithms, the combined study of genomic,
      transcriptional, proteomic, and phenotypic information in well-controlled study
      groups will define a useful conceptual model of pathogenesis and a framework for
      understanding the mechanisms of action of existing therapies for this disorder,
      as well as the rationale for novel curative strategies.

PMID- 15973460
TI  - Association of the lymphotoxin-alpha gene Thr26Asn polymorphism with severity of
      coronary atherosclerosis.
AB  - A recent large-scale, genome-wide association study of single nucleotide
      polymorphisms showed a strong association between susceptibility to myocardial
      infarction and the Thr26Asn polymorphism in the lymphotoxin-alpha (LTA) gene. In
      the present study, we investigated whether the LTA Thr26Asn polymorphism was
      associated with the extent of coronary atherosclerosis in a large cohort (n=1082)
      of well-documented coronary artery disease patients. Thr26Asn genotypes showed a
      significant different distribution in male patients, when stratified according to
      the number of diseased coronary arteries, with an odds ratio of 1.98 (95% CI 1.22
      3.22) for multiple-vessel disease in patients of the Asn/Asn genotype, compared
      with patients of the Thr/Thr or Thr/Asn genotype (P=0.006). Thus, further to the
      recent finding that LTA gene variation is associated with susceptibility to
      coronary heart disease, the present study provides evidence of an association
      between LTA genotype and the extent of coronary atherosclerosis.

PMID- 15973461
TI  - Mapping of interactions and mouse congenic strains identified novel epistatic
      QTLs controlling the persistence of Salmonella Enteritidis in mice.
AB  - The host response to infection in humans is multifactorial and involves the
      complex interaction between two genomes (the host and the pathogen) and the
      environment. Using an experimental mouse model of chronic infection, we have
      previously identified the individual effect of three significant and one
      suggestive quantitative trait loci (QTLs) (Ses1, Ses2, Ses3 and Ses1.1) on
      Salmonella Enteritidis persistence in target organs of 129S6/SvEvTac mice.
      Congenic strain construction was performed by transferring each of these QTLs
      from C57BL/6J onto the 129S6/SvEvTac background, and phenotypic analysis
      confirmed that Ses1 and Ses1.1 contribute to bacterial clearance. Additional QTLs
      regulating Salmonella carriage in 129S6/SvEvTac mice were identified using a two
      locus epistasis QTL linkage mapping approach conducted separately in females and
      males. The epistatic model for females included the individual effect of Ses3 and
      two significant interactions (Ses1-D7Mit267 and Ses1-DXMit48) accounting for 47%
      of the total phenotypic variance. The model for males included the individual
      effect of Ses1.1, three interactions (Ses1-D9Mit218, D2Mit197-D4Mit2 and D3Mit256
      D13Mit36) and explained 47% of the phenotypic variance. Our results suggest that
      the oligogenic nature of Salmonella persistence and epistasis are important
      constituents of the genetic architecture of the host response to chronic
      Salmonella infection.

PMID- 15973462
TI  - Genetic control of parasite clearance leads to resistance to Plasmodium berghei
      ANKA infection and confers immunity.
AB  - Unprecedented cure after infection with the lethal Plasmodium berghei ANKA was
      observed in an F2 progeny generated by intercrossing the wild-derived WLA and the
      laboratory C57BL/6 mouse strains. Resistant mice were able to clear parasitaemia
      and establish immunity. The observed resistance was disclosed as a combinatorial
      effect of genetic factors derived from the two parental strains. Genetic mapping
      of survival time showed that the WLA allele at a locus on chromosome 1
      (colocalizing with Berghei resistance 1 (Berr1), a locus associated with
      resistance to experimental cerebral malaria) increases the probability to resist
      early death. Also, the C57Bl/6 allele at a novel locus on chromosome 9 (Berr3)
      confers overall resistance to this lethal Plasmodium infection. This report
      underlines the value of using wild-derived mouse strains to identify novel
      genetic factors in the aetiology of disease phenotypes, and provides a unique
      model for studying parasite clearance and immunity associated with malaria.

PMID- 15973463
TI  - Peripheral blood gene expression profiling in rheumatoid arthritis.
AB  - We carried out gene expression profiling of peripheral blood mononuclear cells
      (PBMCs) in 29 patients with active rheumatoid arthritis (RA) and 21 control
      subjects using Affymetrix U95Av2 arrays. Using cluster analysis, we observed a
      significant alteration in the expression pattern of 81 genes (P<0.001) in the
      PBMCs of RA patients compared with controls. Many of these genes correlated with
      differences in monocyte counts between the two study populations, and we show
      that a large fraction of these genes are specifically expressed at high levels in
      monocytes. In addition, a logistic regression analysis was performed to identify
      genes that performed best in the categorization of RA and control samples.
      Glutaminyl cyclase, IL1RA, S100A12 (also known as calgranulin or EN-RAGE) and
      Grb2-associated binding protein (GAB2) were among the top discriminators. Along
      with previous data, the overexpression of S100A12 in RA patients emphasizes the
      likely importance of RAGE pathways in disease pathogenesis. The altered
      expression of GAB2, an intracellular adaptor molecule involved in regulating
      phosphatase function, is of particular interest given the recent identification
      of the intracellular phosphatase PTPN22 as a risk gene for RA. These data suggest
      that a detailed study of gene expression patterns in peripheral blood can provide
      insight into disease pathogenesis. However, it is also clear that substantially
      larger sample sizes will be required in order to evaluate fully gene expression
      profiling as a means of identifying disease subsets, or defining biomarkers of
      outcome and response to therapy in RA.

PMID- 15973464
TI  - Impact of tension-free vaginal tape on sexual function: results of a prospective
      study.
AB  - The purpose of this study was to prospectively assess the impact of a TVT
      insertion for the treatment of stress urinary incontinence (SUI) on coital
      incontinence and overall sexual life. Sexually active women with pure SUI and
      without concomitant pelvic organ prolapse scheduled for TVT procedure completed a
      sexual function questionnaire at baseline and 6 months after surgery. Fifty-three
      patients were enrolled. Preoperatively 23 (43.4%) women experienced urine leakage
      during intercourse, 21 (91%) during penetration and 2 (9%) on orgasm. The
      objective cure rate for SUI was 98%. Coital incontinence was cured in 20 of 23
      patients (87%). Thirty-three (62.2%) women reported no change in sexual function
      after surgery and 18 (34%) reported an improvement. Of the latter, 17 (94%) were
      of those cured from coital incontinence. No significant difference in the
      incidence of dyspareunia was found postoperatively. Two patients (3.8%) reported
      intercourse to be worse following surgery, one because of a vaginal erosion and
      one cited de novo anorgasmia as the main reason.

PMID- 15973465
TI  - Fecal incontinence: a review of prevalence and obstetric risk factors.
AB  - Anal incontinence (AI) is a significant problem that causes social and hygienic
      inconvenience. The true prevalence of AI is difficult to estimate due to
      inconsistencies in research methods, but larger studies suggest a rate of 2-6%
      for incontinence to stool. There is a significant association between
      sonographically detected anal sphincter defects and symptoms of AI. The
      intrapartum factors most consistently associated with a higher risk of AI
      include: forceps delivery, third or fourth degree tears, and length of the second
      stage of labor. Fetal weight of > 4,000 g is also associated with AI. Repair of
      the sphincter can be performed in either an overlapping or an end-to-end fashion,
      with similar results for both methods. The role of cesarean delivery for the
      prevention of AI remains unclear, and further study should be devoted to this
      question.

PMID- 15973466
TI  - Histologic evaluation of human cadaveric fascia lata in a rabbit vagina model.
AB  - The purpose of this study was to evaluate the histologic response of human
      cadaveric fascia lata after vaginal implantation. Freeze-dried, gamma-irradiated
      cadaveric fascia lata from three lots was implanted between the rectovaginal
      membrane and vaginal epithelium in New Zealand white rabbits. Rabbits were killed
      at 2, 4, 8, and 12 weeks after implantation. At necropsy, gross findings were
      described and specimens for routine cultures were taken. Histologic evaluation
      determined graft integrity, neovascularization, inflammatory response, and host
      tissue incorporation. Nine rabbits were available for histologic analysis and 14
      for gross and microbiologic analysis. Vaginal erosions occurred with three
      grafts. The remainder were adherent to the surrounding tissues. Erosion was
      associated with bacterial colonization of the graft. Autolysis of one graft
      occurred at 4 weeks. Over time, the inflammatory response decreased and
      neovascularization increased; by 12 weeks, the graft collagen was replaced by
      host collagen. Cadaveric fascia lata serves as scaffolding for host tissue
      incorporation with replacement by host collagen.

PMID- 15973467
TI  - Letter to "prolene tape in the bladder wall after TVT procedure--intramural tape
      placement or secondary tape migration?" and "vaginal wall erosion after
      transobutrator tape procedure".

PMID- 15973468
TI  - Multimerization: closed or open association scenario?
AB  - We address the problem of classification of the type of association
      (multimerization) in solutions of identical unimers. Although the aggregation is
      still routinely characterized in terms of either "open association" or "closed
      association" models, neither of the two models can provide a fair description of
      many aggregation processes. We demonstrate that a realistic multimerization may
      show mixed basic features, i.e. simultaneously those typical of the classical
      open association and those typical of the classical closed association. In
      particular, we show that a living polymerization may seem to exhibit a critical
      micelle concentration (CMC), whereas the basic integral characteristics of a
      "closed" system with rather monodisperse micelles ((m(w)/m(n)(mic) = 1.02) may
      not imply a well-defined CMC. Therefore, a multimerization must be characterized
      by the detailed micelle size distribution that largely defines the equilibrium
      and dynamical properties of the system. To this end, we suggest a simple method
      of deriving the micelle size distribution c(m) (depending also on the total
      concentration of amphiphilic molecules) from the concentration dependence of just
      the mean aggregation number, m(w)(c). Our results thus invite a reconsideration
      of the basic methods used for interpretation of experimental data on
      micellization.

PMID- 15973470
TI  - Health care access for children with special health care needs in California.
AB  - OBJECTIVES: This study examines health care access for children with special
      health care needs (CSHCN) in California, one of the nation's most populous and
      diverse states. METHODS: Data are from the National Survey of Children with
      Special Health Care Needs (NS-CSHCN), a nationally representative survey of
      access for U.S. children fielded by the National Center for Health Statistics
      (NCHS). California CSHCN and those in California's Medicaid program are compared
      with CSHCN elsewhere on child health need, family enabling factors, health care
      enabling factors, system outcomes, and children's experiences with care.
      Multivariable analysis identifies family and health care factors associated with
      system outcomes and children's experiences with health care. RESULTS: California
      parents generally report poorer experiences with care, lower performance on
      systems outcomes, and fewer health care and family enabling factors. The
      magnitude of disparity is greatest for CSHCN in Medi-Cal, although lower-income
      privately insured CSHCN in California also have poorer access than their
      counterparts in other states. Among CSHCN in Medicaid, greater condition impact
      and adolescent age are associated with poorer experiences in California for most
      measures. Disparities between California and other states persist even adjusting
      for family and health care factors in multivariable analysis. CONCLUSIONS:
      Performance gaps in California stem from population differences and apparent
      administrative barriers. Several statewide initiatives are addressing system
      barriers through supports to providers and information to parents.

PMID- 15973471
TI  - A data driven process in Washington State to improve systems of care for children
      with special health care needs: the National Survey of CSHCN.
AB  - OBJECTIVES: The purpose of this article is to present strategies used in one
      state to engage public health stakeholders in the use of National Survey of
      Children With Special Health Care Needs (NS-CSHCN) results to improve systems of
      care for children with special health care needs (CSHCN). This is not a research
      report. METHODS: Seven "CSHCN Road Shows" were conducted with 39 local health
      departments, five state agencies, five parent leaders, three managed health care
      plans, and 12 school nurses. These "CSHCN Road Shows" were used to present and
      validate Washington State findings from the NS-CSHCN, obtain input on additional
      topics for analysis and elicit ways of incorporating NS-CSHCN results into the
      state's MCH Five Year Needs Assessment. RESULTS: Overall, a majority of
      stakeholders reported a high level of interest in using state-level data from the
      NS-CSHCN for local community efforts. Uses included program planning, presenting
      data to local boards of health and other community agencies, and utilizing
      results as talking points with other partners on the needs and unmet needs of the
      population. The state Title V office used feedback from "CSHCN Road Show"
      participants to prioritize program-planning activities, initiate policy
      discussions, and incorporate feedback into the MCH Five Year Needs Assessment.
      CONCLUSIONS: State-level data from the NS-CSHCN are a rich source of information
      for driving improvements in systems of care, facilitating state and local program
      planning efforts, writing grants, and completing MCH Five Year Needs Assessment
      activities.

PMID- 15973472
TI  - Comparing states on outcomes for children with special health care needs.
AB  - OBJECTIVES: To develop two alternative methods for comparing and ranking states
      on the health, health care, and well-being of children with special health care
      needs (CSHCN). METHODS: Fifteen key indicators of CSHCN's functional abilities,
      health insurance coverage, access to care, and the impact of their conditions on
      their families were identified from the 2001 National Survey of Children with
      Special Health Care Needs. An initial composite score for each state was created
      by averaging the state's standardized scores for each of these indicators. Using
      linear regression analyses and standardized residuals, an adjusted composite
      score for each state was then created that accounted for demographic variables
      that differed by state and were related to the initial composite score. States
      were ranked based on the initial and adjusted composite scores. RESULTS: The
      initial composite scores were related to population differences by poverty
      status, African-American race, and the prevalence of special health care needs.
      Compared to ranks based on the initial scores, ranks based on the adjusted scores
      shifted by 10 or more positions for half the states. Hawaii, Rhode Island,
      Arizona, Iowa, and North Dakota had the highest ("best") adjusted scores.
      CONCLUSION: Adjustment to the initial composite scores permits states with
      different demographic compositions to be compared. The adjusted scores may also
      help raise awareness of CSHCN's concerns in states where demographic compositions
      favorable to health outcomes mask the fact that these outcomes are only average
      (or worse) given the states' demographic compositions.

PMID- 15973474
TI  - Characteristics of coordinated ongoing comprehensive care within a medical home
      in Maine.
AB  - OBJECTIVES: Access to coordinated, ongoing comprehensive care in a medical home
      (CCMH) is a national health objective and a federal performance measure. The
      National Survey of Children With Special Health Care Needs (National Survey of
      CSHCN) provides state level data on this Maternal Child Health Bureau performance
      measure. In Maine, only 60% of CSHCN received CCMH in 2001. Here we described
      characteristics of receiving comprehensive care in a medical home for CSHCN, in
      Maine. METHODS: Data from the National Survey of CSHCN were used for the
      analysis. We examined associations between receiving CCMH and demographic
      factors, severity of a condition or problem, and having adequate insurance
      coverage for services in univariate and multivariate logistic regression models.
      RESULTS: The distribution of children who received CCMH did not differ across
      gender, race, age, or poverty level. Children with adequate insurance were more
      likely to have received this care than those without adequate insurance and those
      with a more severe condition or problem were less likely to receive CCMH.
      CONCLUSIONS: We found that receiving CCMH was positively related to adequate
      insurance, independent of poverty. We also found that CSHCN with more severe
      conditions have more unmet needs than those with less severe conditions. CSHCN
      programs, which have a responsibility to assure that CSHCN receive CCMH, must
      work to maximize insurance coverage. Programs can also work to raise awareness
      among providers of the complexity of CCMH and the role it plays in maximizing the
      health of the child and family.

PMID- 15973475
TI  - Factors associated with health care access for Mississippi children with special
      health care needs.
AB  - OBJECTIVES: This purpose of the study was to examine the factors associated with
      access to routine care and to specialty care for Mississippi children with
      special health care needs (CSHCN). METHODS: We analyzed data for Mississippi
      CSHCN from the 2001 National Survey of Children with Special Health Care Needs.
      Using a modified version of Andersen and Aday's Behavioral Model of Health
      Services Use, we explored the relationship of independent variables (e.g.,
      demographics, insurance, severity of illness) to dependent variables (did not
      obtain routine care, did not obtain specialty care). We conducted bivariate and
      logistic regression analyses using SAS and SUDAAN. RESULTS: Based on self
      reported data, with a 61% response rate, 66% of Mississippi CSHCN needed routine
      health care, and 52.8% needed specialty care. Of these children, 6.5% did not
      receive routine care and 9.3% did not receive specialty care. In a fully adjusted
      model, discontinuous insurance coverage was an important factor associated with
      not having obtained routine care (OR = 7.8; CI = 1.7-35.9) and specialty care (OR
      = 8.6; CI = 2.0-36.8). Children with a high illness severity rank were more
      likely to have not obtained routine care than children with a low rank (OR 1.4;
      CI = 1.1-1.9). CONCLUSIONS: It may be important to establish a health insurance
      safety net for families who lack insurance continuity since it appears that a
      lapse in insurance coverage impedes health care access. Further research is
      needed to understand the relationship between illness severity and lack of health
      care access, especially for children with special health care needs.

PMID- 15973476
TI  - Economic impact on families caring for children with special health care needs in
      New Hampshire: the effect of socioeconomic and health-related factors.
AB  - OBJECTIVES: To describe the economic impact on families of caring for children
      with special health care needs (CSHCN), and to determine the relative
      contributions of socioeconomic and health-related factors to these impacts on
      families in the State of New Hampshire. METHODS: Seven hundred and fifty families
      with CSHCN in New Hampshire were interviewed in the National Survey of Children
      with Special Health Needs. Among respondents with CSHCN, univariate and bivariate
      analyses were conducted to examine economic impact and independent factors
      (income, insurance type, and impact of condition). Multiple logistic and linear
      regression models were used to examine relationships between impact and
      independent factors, controlling for race/ethnicity. RESULTS: Compared to typical
      children, CSHCN were more likely to have public insurance (12% and 21%,
      respectively) and less likely to live in higher income families (56% and 48%,
      respectively). Among CSHCN, nearly one-quarter were greatly affected by their
      condition, 31% had inadequate insurance, families of 21% had financial problems,
      parents of 27% had to cut work hours, and almost 15% needed professional care
      coordination. Adjusting for other factors in regression models, the impact of the
      condition was associated with all measures of impact, insurance type was
      associated with out-of-pocket costs, and income was associated with the total
      number of impacts. Parents of children who are usually or always affected by
      their conditions were 14 times more likely than those who are never affected to
      need care coordination. CONCLUSION: A family's need for support services, and
      particularly for care coordination, may depend less on the family's means than on
      the impact of their child's condition.

PMID- 15973477
TI  - Are rates of functional limitations associated with access to care? A state-level
      analysis of the national survey of children with special health care needs.
AB  - OBJECTIVES: Health-related services and compensatory mechanisms have a potential
      role in minimizing functional limitations and increasing quality of life among
      children with special health care needs (CSHCN). We examined whether rates of
      functional limitations among CSHCN in the 50 states and District of Columbia were
      associated with state-level characteristics that reflect access to such services
      among CSHCN. METHODS: We aggregated child-level survey data from the National
      Survey of CSHCN to create 51 state-level estimates of the proportions who had
      functional limitations, had >/=1 unmet health needs, and lacked medical insurance
      coverage. State-level information about Medicaid spending per child enrollee in
      federal fiscal year 2000 was obtained from The Henry J. Kaiser Family Foundation
      website. We examined correlations between the percentages of CSHCN having
      functional limitations and each of the other state-level variables, and conducted
      multiple regression analyses that examined these associations while controlling
      for the statewide percentages of children living in poverty. RESULTS: The
      proportions of CSHCN with functional limitations were higher in states with
      higher rates of uninsured CSHCN (r = .49; p < .0001) and higher rates of CSHCN
      with unmet health needs (r = .62; p < .0001). Proportions of CSHCN with
      functional limitations were unrelated to per child Medicaid spending. These
      findings were robust when we controlled for percentages of children in poverty
      across states. CONCLUSIONS: Fewer unmet needs for health-related services are
      associated with lower statewide rates of functional limitations in CSHCN. As
      health care costs increase and state revenues decrease, CSHCN are at increasing
      risk of losing access to required services. Were this to happen we might expect
      an increase in the proportion of CSHCN who experience significant functional
      limitations. Thus, a key challenge is to provide CSHCN access to the amount and
      quality of health-related care they require to achieve their potential.

PMID- 15973478
TI  - The need for care coordination among children with special health care needs in
      Illinois.
AB  - OBJECTIVES: The objectives of this study were: 1) to estimate the need for care
      coordination among children with special health care needs (CSHCN) in Illinois,
      2) to assess the need for care coordination among CSHCN in Illinois by
      sociodemographic, condition-related, and access to care factors, and 3) to
      discuss approaches for meeting the need for care coordination. METHODS: The study
      included 745 Illinois families interviewed as part of the State and Local Area
      Integrated Telephone Survey (SLAITS) of CSHCN. Classifying families of CSHCN as
      needing care coordination was based on three survey questions. The prevalence of
      the need for care coordination among CSHCN in Illinois was examined overall and
      by sociodemographic characteristics, descriptors of the child's health condition,
      and measures of access to services. Multivariable modeling was carried out to
      jointly assess these factors and the need for care coordination. RESULTS: In
      Illinois, 25.2% of CSHCN families reported a need for care coordination.
      Condition severity, need for supplementary/ancillary services, lack of insurance
      coverage and inadequate communication among providers were significantly
      associated with the need for care coordination (OR = 1.14, OR = 1.72, OR = 2.45,
      and OR = 3.08, respectively). Having a primary care provider/medical home was not
      associated with the need for care coordination in multivariable analysis.
      CONCLUSION: Coordination of health services is important for all children and all
      adults, but it is particularly important for children with special health care
      needs. The variation in the need for care coordination both within and across
      states underscores the need for flexibility in program and policy development for
      CSHCN.

PMID- 15973479
TI  - CSHCN in Texas: meeting the need for specialist care.
AB  - OBJECTIVE: Assuring the sufficiency and suitability of systems of care and
      services for children with special health care needs (CSHCN) presents a challenge
      to Texas providers, agencies, and state Title V programs. To meet the need for
      specialist care, referrals from primary care doctors are often necessary. The
      objective of this study was to describe the factors associated with the need for
      specialist care and problems associated with obtaining referrals in Texas.
      METHODS: Bivariate and multivariate analyses were performed using the National
      Survey of Children with Special Health Care Needs (NS-CSHCN) weighted sample for
      Texas (n = 719,014) to identify variables associated with the need for specialist
      care and problems obtaining referrals for specialist care. RESULTS: Medical need
      of the CSHCN and sensitivity to family values/customs was associated with greater
      need for specialist care, and Hispanic ethnicity and lower maternal education
      were associated with less need. Medical need, amount of time spent with doctors
      and sensitivity to values/customs, living in a large metropolitan statistical
      area, and lack of medical information were associated with problems obtaining a
      specialist care referral. CONCLUSIONS: Findings revealed some similarities and
      differences with meeting the need for specialist care when comparing Texas
      results to other studies. In Texas, aspects of customer satisfaction variables,
      especially doctors' sensitivity to family values/customs and parents' not
      receiving enough information on medical problems, were significantly associated
      with problems obtaining specialist referrals. Findings indicate a need to further
      research relationships and communication among doctors, CSHCN, and their
      families.

PMID- 15973480
TI  - Impact of caring for children with special health care needs on the family: Rhode
      Island's experience.
AB  - OBJECTIVES: The impact of caring for children with special health care needs
      (CSHCN) on their families' finances and employment was studied. METHODS: Data
      from the 2001 National Survey of Children with Special Health Care Needs were
      used to measure financial and employment problems. The level of impact was
      examined by child's age, gender, ethnicity, race, mother's education, poverty
      status, and severity of the child's condition. The association between core
      outcome measures and the level of family impact was determined after adjusting
      for potential confounding factors. RESULTS: Financial or employment problems were
      more likely to occur among families with young children, with incomes below 200%
      poverty and with children whose condition usually/always affected their
      activities. Compared to families without these problems, impacted families were
      less likely to partner in decision making, be satisfied with services, receive
      comprehensive care in a medical home, have adequate health insurance, and feel
      service systems are organized for easy use. CONCLUSIONS: Many families of CSHCN
      face financial and employment problems and are less likely to have a medical
      home, adequate insurance, and access to health care services.

PMID- 15973481
TI  - Defining underinsurance among children with special health care needs: a Virginia
      sample.
AB  - OBJECTIVES: The study sought to: 1) examine the national Children with Special
      Health Care Needs (CSHCN) survey to determine whether there are items that can
      serve to operationalize alternative definitions of underinsurance; 2) construct
      definitions from the survey items that are consistent with Structural and
      Economic definitions of underinsurance and devise an algorithm for determining
      underinsurance for each; and 3) compare these two underinsurance definitions with
      the Maternal and Child Health definition of inadequate insurance, a definition
      that takes an Attitudinal approach to the construct. METHODS: Analyses included
      Virginia children who were insured throughout the survey period. Survey items
      from the national CSHCN survey were examined to identify items related to
      underinsurance. Items were divided into groups corresponding to three definitions
      of insurance (Attitudinal, Structural, and Economic). Algorithms were
      established, and underinsurance rates calculated for each definition. Logistic
      regression models were constructed to investigate demographic characteristics
      related to underinsurance. RESULTS: Different percentages of Virginia CSHCN were
      found to be underinsured based on the definitions of Attitudinal (28.9%),
      Economic (25.6%), and Structural (2.9%). Eight demographic characteristics and
      the pervasiveness of the child's special health care needs were examined in
      relation to underinsurance. For the Attitudinal definition, poverty level and
      pervasiveness were significant predictors in the model. In the model predicting
      Economic underinsurance status, pervasiveness and three of the demographic
      characteristics significantly predicted underinsurance status. In the
      multivariate logistic regression model for the Structural definition, none of the
      predictors was significantly related to underinsurance. CONCLUSIONS: These
      findings demonstrate that alternative definitions of underinsurance yield
      dramatically different underinsurance rates. Further, even when yielding similar
      rates, alternative definitions may identify substantially different sets of
      children. The likelihood of being underinsured has a strong association with low
      income status and pervasiveness of the child's special health care needs.
      Understanding these factors and their implications will be important when
      planning accessible and comprehensive health plans and care systems for CSHCN.

PMID- 15973482
TI  - Delayed and forgone care for children with special health care needs in New York
      State.
AB  - OBJECTIVE: To identify characteristics associated with delayed/forgone care for
      children with special health care needs (CSHCN) in New York State (NYS) as
      reported by their parents. METHODS: Data come from NYS participants in the 2000
      2002 National Survey of Children with Special Health Care Needs. Data were
      analyzed using weighted bivariate and multivariate regression models. The
      dependent variable was report of delayed/forgone routine health care. Independent
      variables included illness characteristics, potential and actual access to care,
      and provider care characteristics. RESULTS: In NYS, 8.4% reported delayed/forgone
      health care for their child. Parents of children with delayed/forgone care were
      more likely to report that their child was uninsured (adjusted odds ratio [aOR]
      3.8, 95% confidence interval [CI] 1.3-11.8), had experienced interrupted health
      insurance (aOR 3.9, 95% CI 1.5-9.7), or their child's insurance was not adequate
      for CSHCN (aOR 3.6, 95% CI 1.4-9.1). Further, these parents were more likely to
      report that providers never spend adequate time (aOR 6.3, 95% CI 1.2-34.4),
      provide sufficient information (aOR 8.0, 95% CI 2.5-25.0), act as partners in
      care (aOR 6.7, 95% CI 2.3-19.7), or display cultural sensitivity (aOR 5.4, 95% CI
      1.2-24.3). CONCLUSIONS: An estimated 40,771 NYS CSHCN experience delayed/forgone
      routine health care. Their families report two noteworthy barriers: inadequate or
      discontinuous insurance coverage and poor communication with health-care
      providers. Access to care for CSHCN can be improved by increasing consistent
      comprehensive insurance coverage and increasing sensitivity in relationships
      between health care providers and families of CSHCN.

PMID- 15973483
TI  - The association of child condition severity with family functioning and
      relationship with health care providers among children and youth with special
      health care needs in Alabama.
AB  - OBJECTIVE: The purpose of the present study is to assess how the severity of a
      child's condition affects family functioning and the relationship with health
      care providers among children with special health care needs in Alabama. METHODS:
      Using the data from the National Survey of Children with Special Health Care
      Needs (CSHCN), three variables were used as measures of condition severity:
      responses to the CSHCN screener questions, whether condition affected the ability
      to do things for children and youth with special health care needs (CYSHCN), and
      the level of severity of CYSHCN's condition. The dependent variables included
      family functioning and provider relationship. RESULTS: CYSHCN who only take
      prescription medicine for their chronic condition (MO) had lower condition
      severity from those who have other needs (NMO). In NMO CYSHCN, higher condition
      severity was associated with increased strain on family functioning outcomes and
      higher unmet needs in provider relationship outcomes, adjusted for demographic
      and insurance variables. Families of NMO CYSHCN with a more severe condition
      spent more temporal and financial resources and had a higher need for
      professional care coordination, and were less likely to have sensitive providers.
      CONCLUSIONS: Severity of condition is an important factor increasing strain on
      family resources and relationship with the provider. Our results indicate the
      need for professional care coordination and family support, particularly among
      those families in which there is a NMO CYSHCN with a more severe condition. This
      finding supports the mandate that all CYSHCN should have their health care
      coordinated and provided in the context of a medical home.

PMID- 15973484
TI  - Factors associated with ease of using community-based systems of care for CSHCN
      in Hawai'i.
AB  - OBJECTIVES: To study factors contributing to difficulty using community-based
      services by families of children with special health care needs (CSHCN) in
      Hawai'i. METHODS: Data source was the 2001 National Survey of Children With
      Special Health Care Needs. The study population included the 449 respondents who
      were surveyed after additional items were added to the original questionnaire.
      Outcome of interest was "% of CSHCN whose families report community-based service
      systems are organized so they can use them easily." Explanatory variables
      included child health conditions (functional limitation, degree of severity,
      types of service needs), child and family characteristics (child age, maternal
      education, poverty level), and health services characteristics (partnership of
      family in decision making, family-centered coordinated care, adequate health
      insurance). RESULTS: Children with special health care needs comprised 11.0% of <
      18 years old children. Overall, 69% of respondents reported that community-based
      services could be used easily. Logistic regression analysis showed that the odds
      of reporting difficulties in using community-based services were almost 5 times
      higher for families who did not partner in decision making, 2.9 times higher for
      families who did not receive family-centered coordinated care, and 2.7 times
      higher for families who did not have adequate health insurance compared with
      families who were satisfied with the care received. Need for services contributed
      independently to reporting difficulties in community-based service use. Contrary
      to the hypothesized associations, severe health conditions or limited
      functionality did not contribute significantly to reporting difficulties in
      service use. CONCLUSIONS: Families who reported difficulties in using community
      based services were those who have children who need extensive and varied
      services. Lack of involvement in decision making, lack of coordinated care in a
      medical home, and insufficient health insurance were the main obstacles to their
      ability to use community-based services easily.

PMID- 15973485
TI  - Industrial importance of the genus Brevibacterium.
AB  - The genus Brevibacterium has long been difficult for taxonomists to classify due
      to its close morphological similarity to other genera. Since it was proposed in
      1953, the genus has often been redefined. The genus is best known for its
      important role in the ripening of certain cheeses (B. linens) and for its
      supposed over-production of L: -amino acids. Other interesting industrial
      applications, including the production of ectoine, have recently been proposed.
      The general characteristics, the occurrence and the recent taxonomy of
      Brevibacterium are reviewed here. Furthermore, known and potential industrial
      applications for Brevibacterium species are briefly discussed.

PMID- 15973486
TI  - Phospholipase D and its application in biocatalysis.
AB  - Phospholipase D (PLD) from plants or microorganisms is used as biocatalyst in the
      transformation of phospholipids and phospholipid analogs in both laboratory and
      industrial scale. In recent years the elucidation of the primary structure of
      many PLDs from several sources, as well as the resolution of the first crystal
      structure of a microbial PLD, have yielded new insights into the structural basis
      and the catalytic mechanism of this catalyst. This review summarizes some new
      results of PLD research in the light of application.

PMID- 15973487
TI  - Sequence analysis, cloning and over-expression of an endoxylanase from the
      alkaliphilic Bacillus halodurans.
AB  - The BhMIR32 xyn11A gene, encoding an extracellular endoxylanase of potential
      interest in bio-bleaching applications, was amplified from Bacillus halodurans
      MIR32 genomic DNA. The protein encoded is an endo-1,4-beta-xylanase belonging to
      family 11 of glycosyl hydrolases. Its nucleotide sequence was analysed and the
      mature peptide was subcloned into pET22b(+) expression vector. The enzyme was
      over-expressed in a high density Escherichia coli culture as a soluble and active
      protein, and purified in a single step by immobilised metal ion affinity
      chromatography with a specific activity of 3073 IU mg-1.

PMID- 15973488
TI  - Synthesis of hydroquinone-alpha-glucoside by alpha-glucosidase from baker's
      yeast.
AB  - Hydroquinone-alpha-glucoside was synthesised from hydroquinone and maltose as
      glucosyl donor by transglucosylation in a water system with alpha-glucosidase
      from baker's yeast. Only one phenolic -OH group was alpha-anomer-selectively
      glucosylated. The optimum conditions for transglucosylation reaction were at 30
      degrees C for 20 h with 50 mM: hydroquinone and 1.5 M: maltose in 100 mM: sodium
      citrate/phosphate buffer at pH 5.5. The glucoside was obtained at 0.6 mg/ml with
      a 4.6% molar yield with respect to hydroquinone.

PMID- 15973489
TI  - Electrochemical oxidation of water by a cellobiose dehydrogenase from
      Phanerochaete chrysosporium.
AB  - Cellobiose dehydrogenase (CDH) is a redox protein containing two electron
      transfer centers; a flavin coenzyme performing a two-electron transfer reaction
      and an iron-heme coenzyme facilitating single-electron transfer. Purified CDH
      from Phanerochaete chrysosporium was immobilized on a pyrolytic graphite
      electrode and electron transfer from cellobiose to the electrode was generated.
      With cellobiose present during cyclic voltammetry, this novel enzyme/electrode
      system exhibited sharp, stable oxidation peaks with slower, though equivalent,
      reduction peaks. During cyclic voltammetry without substrate, the enzyme was
      rapidly oxidized during the initial scan, with no corresponding enzyme reduction
      during the reducing half of the cycle. After resting for several hours in aqueous
      buffer, the full oxidation current appeared again. These results suggest that the
      CDH is reduced by water splitting, albeit at a slow rate.

PMID- 15973490
TI  - Tributyl phosphate degradation by Rhodopseudomonas palustris and other
      photosynthetic bacteria.
AB  - Tributyl phosphate (TBP) is widely used in nuclear fuel processing and other
      waste generating chemical industries. Although TBP is bacteriostatic, some
      microbes are resistant to it and may degrade it. Under dark aerobiosis, purple
      non-sulfur photosynthetic bacteria degraded up to 0.6 mM TBP, initially present
      at 2 mM, within 3 weeks and under photosynthetic conditions, Rhodopseudomonas
      palustris degraded 1.6 mM TBP within 3 weeks. The curing of the Rhodopseudomonas
      palustris endogenous plasmid demonstrated that the genes involved in the TBP
      degradation are chromosomal.

PMID- 15973491
TI  - Tumor-specific gene delivery using RNA-targeting Tetrahymena group I intron.
AB  - Current gene therapy protocols against cancer often have limited target
      specificity. Here, a novel tumor-specific targeted gene delivery procedure, which
      is based on Tetrahymena group I intron ribozyme, is presented. This ribozyme can
      target a cancer-specific transcript and then replace the RNA with new
      transcripts, resulting in induction of the transgene activity selectively in
      cancer cells that express the target RNA. The RNA replacement occurs by trans
      splicing reaction with high fidelity with the target RNA. In addition, the
      ribozyme can specifically inhibit function of the targeted gene in the cells
      expressing the RNA. Moreover, the ribozyme can selectively deliver cytotoxin gene
      activity into cancer cells expressing the RNA and thereby specifically hampers
      the survival of these cells. These findings suggest that the trans-splicing
      ribozyme that targets the cancer-specific RNA could be a potential agent for
      specific tumor gene therapy.

PMID- 15973492
TI  - Cells of Candida utilis for in vitro (R)-phenylacetylcarbinol production in an
      aqueous/octanol two-phase reactor.
AB  - (R)-Phenylacetylcarbinol (PAC), a pharmaceutical precursor, was produced from
      benzaldehyde and pyruvate by pyruvate decarboxylase (PDC) of Candida utilis in an
      aqueous/organic two-phase emulsion reactor. When the partially purified enzyme in
      this previously established in vitro process was replaced with C. utilis cells
      and the temperature was increased from 4 to 21 degrees C, a screen of several 1
      alcohols (C4-C9) confirmed the suitability of 1-octanol as the organic phase.
      Benzyl alcohol, the major by-product in the commercial in vivo conversion of
      benzaldehyde and sugar to PAC by Saccharomyces cerevisiae, was not formed. With a
      phase volume ratio of 1:1 and 5.6 g C. utilis l-1 (PDC activity 2.5 U ml-1), PAC
      levels of 103 g l-1 in the octanol phase and 12.8 g l-1 in the aqueous phase were
      produced in 15 h at 21 degrees C. In comparison to our previously published
      process with partially purified PDC in an aqueous/octanol emulsion at 4 degrees
      C, PAC was produced at a 4-times increased specific rate (1.54 versus 0.39 mg U-1
      h-1) with simplified catalyst production and reduced cooling cost. Compared to
      traditional in vivo whole cell PAC production, the yield on benzaldehyde was 26%
      higher, the product concentration increased 3.9-fold (or 6.9-fold based on the
      organic phase), the productivity improved 3.1-fold (3.9 g l-1 h-1) and the
      catalyst was 6.9-fold more efficient (PAC/dry cell mass 10.3 g g-1).

PMID- 15973493
TI  - Induction method of tyrosine kinase A-mediated cell death in rat
      pheochromocytoma.
AB  - Nerve Growth Factor (NGF) is a neurotrophic factor that prevents apoptosis in
      neuronal progenitor cells. In rat pheochromocytoma (PC12) cells, tyrosine kinase
      A receptor (TrkA) mediates neurotrophic or protective effects, while p75
      neurotrophin receptor (p75NTR) functions as a death receptor. We have determined
      whether TrkA mediates any cytotoxic effect. Following serum deprivation, TrkA
      expression increased 2.2-fold and apoptosis began with expression of Bax
      proapoptotic protein. Application of NGF halved cell viability but this was
      reversed by K252a, the TrkA inhibitor. These results confirmed the paradoxical
      cytotoxic effect of neurotrophic NGF via TrkA in PC12 cells following serum
      deprivation.

PMID- 15973494
TI  - Cloning and characterization of the Cu,Zn superoxide dismutase (SOD1) cDNA from
      the mole cricket, Gryllotalpa orientalis.
AB  - A Cu,Zn superoxide dismutase (SOD1) cDNA was cloned from the mole cricket,
      Gryllotalpa orientalis. The G. orientalis SOD1 (GoSOD1) cDNA contains an open
      reading frame of 462 bp encoding 154 amino acid polypeptide with a predicted
      molecular mass of 15.8 kDa and pI of 6.1, and possesses the typical metal binding
      ligands of six histidines and one aspartic acid common to SOD1s. The deduced
      amino acid sequence of the GoSOD1 cDNA showed 75% identity to Lasius niger SOD1,
      73% to Apis mellifera SOD1, and 70-68% to SOD1 sequences from other insects.
      Northern blot analysis revealed the presence of GoSOD1 transcripts in all tissues
      examined. The expression level of GoATX1 mRNA in the fat body was induced when G.
      orientalis adult was exposed at low (4 degrees C) and high (37 degrees C)
      temperatures, suggesting that the GoSOD1 seems to play a protective role against
      oxidative stress caused by temperature shock.

PMID- 15973495
TI  - A gene selection algorithm based on the gene regulation probability using maximal
      likelihood estimation.
AB  - A novel gene selection algorithm based on the gene regulation probability is
      proposed. In this algorithm, a probabilistic model is established to estimate
      gene regulation probabilities using the maximum likelihood estimation method and
      then these probabilities are used to select key genes related by class
      distinction. The application on the leukemia data-set suggests that the defined
      gene regulation probability can identify the key genes to the acute lymphoblastic
      leukemia (ALL)/acute myeloid leukemia (AML) class distinction and the result of
      our proposed algorithm is competitive to those of the previous algorithms.

PMID- 15973499
TI  - Reciprocal chromosome painting between two South American bats: Carollia
      brevicauda and Phyllostomus hastatus (Phyllostomidae, Chiroptera).
AB  - The Neotropical Phyllostomidae family is the third largest in the order
      Chiroptera, with 56 genera and 140 species. Most researchers accept this family
      as monophyletic but its species are anatomically diverse and complex, leading to
      disagreement on its systematics and evolutionary relationships. Most of the
      genera of Phyllostomidae have highly conserved karyotypes but with intense
      intergeneric variability, which makes any comparative analysis using classical
      banding difficult. The use of chromosome painting is a modern way of genomic
      comparison on the cytological level, and will clarify the intense intergenus
      chromosomal variability in Phyllostomidae. Whole chromosome probes of species
      were produced as a tool for evolutionary studies in this family from two species
      from different subfamilies, Phyllostomus hastatus and Carollia brevicauda, which
      have large morphological and chromosomal differences, and these probes were used
      in reciprocal chromosome painting. The hybridization of the Phyllostomus probes
      on the Carollia genome revealed 24 conserved segments, while the Carollia probes
      on the Phyllostomus genome detected 26 segments. Many chromosome rearrangements
      have occurred during the divergence of these two genera. The sequence of events
      suggested a large number of rearrangements during the differentiation of the
      genera followed by high chromosomal stability within each genus.

PMID- 15973500
TI  - Chromosome evolution and improved cytogenetic maps of the Y chromosome in cattle,
      zebu, river buffalo, sheep and goat.
AB  - Comparative FISH-mapping among Y chromosomes of cattle (Bos taurus, 2n = 60, BTA,
      submetacentric Y chromosome), zebu (Bos indicus, 2n = 60, BIN, acrocentric Y
      chromosome but with visible small p-arms), river buffalo (Bubalus bubalis, 2n =
      50, BBU, acrocentric Y chromosome), sheep (Ovis aries, 2n = 54, OAR, small
      metacentric Y chromosome) and goat (Capra hircus, 2n = 60, CHI, Y-chromosome as
      in sheep) was performed to extend the existing cytogenetic maps and improve the
      understanding of karyotype evolution of these small chromosomes in bovids. C- and
      R-banding comparison were also performed and both bovine and caprine BAC clones
      containing the SRY, ZFY, UMN0504, UMN0301, UMN0304 and DYZ10 loci in cattle and
      DXYS3 and SLC25A6 in goat were hybridized on R-banded chromosomes by FISH. The
      main results were the following: (a) Y-chromosomes of all species show a typical
      distal positive C-band which seems to be located at the same region of the
      typical distal R-band positive; (b) the PAR is located at the telomeres but close
      to both R-band positive and ZFY in all species; (c) ZFY is located opposite
      SRYand on different arms of BTA, BIN, OAR/CHI Y chromosomes and distal (but
      centromeric to ZFY) in BBU-Y; (d) BTA-Y and BIN-Y differ as a result of a
      centromere transposition or pericentric inversion since they retain the same gene
      order along their distal chromosome regions and have chromosome arms of different
      size; (e) BTA-Y and BBU-Y differ in a pericentric inversion with a concomitant
      loss or gain of heterochromatin; (f) OAR/CHI-Y differs from BBU-Y for a
      pericentric inversion with a major loss of heterochromatin and from BTA and BIN
      for a centromere transposition followed by the loss of heterochromatin.

PMID- 15973501
TI  - Caenorhabditis elegans Elongin BC complex is essential for cell proliferation and
      chromosome condensation and segregation during mitosis and meiotic division II.
AB  - The ubiquitin-mediated protein degradation system is involved in a wide variety
      of cellular functions. The RING-H2 finger protein RBX1 is a common subunit of
      Cullin-based ubiquitin ligases. Caenorhabditis elegans RBX1 and CUL2 are
      essential for regulating chromosome condensation and segregation during mitosis
      and meiosis and are also critical for cell proliferation. Here, we demonstrate
      that Elongin B (ELB1) and C (ELC1) form a stable complex, and that depletion of
      either gene product by RNA-mediated interference (RNAi) causes pronounced defects
      in the second meiotic division. Embryos and adults that escape meiotic arrest
      have several irregular phenotypes. These include defects in mitotic chromosomal
      condensation and segregation, pronuclear rotation, and germ cell proliferation,
      abnormal cortical protrusion, and accumulation of the cyclin-dependent kinase
      inhibitor CKI1. All these defects are consistent with those found after depletion
      of CUL2. In addition, direct interaction between ELC1 and CUL2 is revealed by
      bacterial two-hybrid analysis. Thus, the RBX1/CUL2/ELC1/ELB1 complex acts as an
      E3 ubiquitin ligase in C. elegans and is essential for diverse functions relevant
      to chromosomal dynamics and cell cycle control.

PMID- 15973502
TI  - Does radial nuclear organisation influence DNA damage?
AB  - It has been suggested that chromatin at the nuclear periphery could act to shield
      DNA sequences in the nuclear interior from damage. To test this hypothesis, we
      have examined the nuclear distribution of sites of DNA repair induced by
      oxidation or UV-C. We do not detect more damage (repair) at the nuclear periphery
      than in the nuclear interior. In fact, contrary to the body guard hypothesis,
      there is an excess of damage detected in the nuclear interior. This is further
      supported by sequence comparison between genes on human chromosomes 18 or 19, and
      their counterparts in the chimpanzee. The synonymous substitution rate for genes
      on chromosome 19, which is located towards the centre of the human nucleus, was
      higher than that for genes on chromosome 18, which is located at the nuclear
      periphery. We conclude that chromatin at the periphery of the human nucleus is
      not able to protect more internally located sequences from damage and mutation.
      We suggest that features of the chromatin structure, or base composition, of
      sequences in the nuclear centre make them more susceptible to damage.

PMID- 15973503
TI  - Phylogenomic study of the subfamily Caprinae by cross-species chromosome painting
      with Chinese muntjac paints.
AB  - Chromosomal homologies have been established between the Chinese muntjac
      (Muntiacus reevesi, MRE, 2n = 46) and five ovine species: wild goat (Capra
      aegagrus, CAE, 2n = 60), argali (Ovis ammon, OAM, 2n = 56), snow sheep (Ovis
      nivicola, ONI, 2n = 52), red goral (Naemorhedus cranbrooki, NCR, 2n = 56) and
      Sumatra serow (Capricornis sumatraensis, CSU, 2n = 48) by chromosome painting
      with a set of chromosome-specific probes of the Chinese muntjac. In total, twenty
      two Chinese muntjac autosomal painting probes detected thirty-five homologous
      segments in the genome of each species. The chromosome X probe hybridized to the
      whole X chromosomes of all ovine species while the chromosome Y probe gave no
      signal. Our results demonstrate that almost all homologous segments defined by
      comparative painting show a high degree of conservation in G-banding patterns and
      that each speciation event is accompanied by specific chromosomal rearrangements.
      The combined analysis of our results and previous cytogenetic and molecular
      systematic results enables us to map the chromosomal rearrangements onto a
      phylogenetic tree, thus providing new insights into the karyotypic evolution of
      these species.

PMID- 15973504
TI  - Autosomal location of genes from the conserved mammalian X in the platypus
      (Ornithorhynchus anatinus): implications for mammalian sex chromosome evolution.
AB  - Mammalian sex chromosomes evolved from an ancient autosomal pair. Mapping of
      human X- and Y-borne genes in distantly related mammals and non-mammalian
      vertebrates has proved valuable to help deduce the evolution of this unique part
      of the genome. The platypus, a monotreme mammal distantly related to eutherians
      and marsupials, has an extraordinary sex chromosome system comprising five X and
      five Y chromosomes that form a translocation chain at male meiosis. The largest X
      chromosome (X1), which lies at one end of the chain, has considerable homology to
      the human X. Using comparative mapping and the emerging chicken database, we
      demonstrate that part of the therian X chromosome, previously thought to be
      conserved across all mammals, was lost from the platypus X1 to an autosome. This
      region included genes flanking the XIST locus, and also genes with Y-linked
      homologues that are important to male reproduction in therians. Since these genes
      lie on the X in marsupials and eutherians, and also on the homologous region of
      chicken chromosome 4, this represents a loss from the monotreme X rather than an
      additional evolutionary stratum of the human X.

PMID- 15973505
TI  - Alphoid DNA from different chromosomes forms de novo minichromosomes with high
      efficiency.
AB  - Clones from one BAC and one PAC library carrying centromeric alphoid DNA were
      characterized and found to be stable but to differ according to the enzyme used
      to make the library. Five different clones with homogeneous alphoid DNA, derived
      from chromosomes 13/21, 14/22, 17 and 18, were all shown to form minichromosomes
      de novo after transfection into the human cell line HT1080 in greater than 29% of
      the cell lines analysed. Similarly sized alphoid arrays (110-160 kb) from
      chromosomes 17, 13/21 and 14/22 all formed minichromosomes in about 50% of the
      cell lines analysed while a smaller array (50 kb) of 14/22 alphoid was less
      efficient (29% of cell lines) and a larger array (200 kb) from chromosome 18 was
      more efficient (2/2 cell lines). Thus the larger arrays of alphoid DNA gave
      higher percentages of cell lines with minichromosomes. However, smaller arrays
      may be preferable for gene expression as there appeared to be more EGFP
      expression from these minichromosomes.

PMID- 15973506
TI  - Central administration of perfluorooctanoic acid inhibits cutaneous inflammation.
AB  - OBJECTIVE: To elucidate the site of action of perfluorooctanoic acid (PFOA) in
      the carrageenan model of peripheral inflammation. SUBJECTS: Male Sprague-Dawley
      rats. TREATMENT: We first compared the anti-edema effects of systemic PFOA (50
      150 mg/kg) with prototypical nonsteroidal (acetylsalicylic acid, ASA, 50-200
      mg/kg) and steroidal (dexamethasone, 0.5-5.0 mg/kg) drugs after the intraplantar
      injection of carrageenan (1%). We then compared the anti-edema effects of
      systemic PFOA with local intraplantar (10 mg/kg), and intracerebroventricular
      (i.c.v., 0.1-50 mug) routes of administration. RESULTS: Systemic PFOA was at
      least as or more efficacious than ASA or dexamethasone in reducing carrageenan
      induced edema. RU-486 did not change the anti-edema effect of PFOA, ruling out a
      contribution of endogenous release of glucorticoids. I. c. v. PFOA, but not
      perfluorooctanes, dramatically reduced multiple signs of inflammation at doses
      well below the systemically-effective dose. We conclude that the anti-edema
      effect of high systemic doses of PFOA (> or =100 mg/kg, i. p.) is mediated in
      part by actions in the brain.

PMID- 15973507
TI  - Ultrasonically nebulized distilled water prevents exogenous histamine
      hyperreactivity in Toxocara canis-infected mice.
AB  - OBJECTIVE: This study examines the effect of ultrasonically nebulized distilled
      water inhalation on the systemic histamine hyperreactivity of Toxocara canis
      infected mice. METHODS: Uninfected and T. canis-infected mice received an
      intravenous sublethal dose of histamine and lethality rates were documented. At
      24 days post infection, infected mice received ultrasonically nebulized distilled
      water inhalation for 1 h. Twenty-four hours later histamine levels were
      determined in bronchoalveolar lavage fluid as well as histamine lethality and
      toluidine blue-stained mast cell number in the lung. RESULTS: T. canis-infected
      mice showed increased lethality after exposure to histamine in comparison to
      uninfected mice. Ultrasonically nebulized distilled water inhalation prevented
      histamine-induced lethality and reduced toluidine blue-stained mast cell numbers
      in the lung. CONCLUSIONS: The correlation between decreases in stained mast cells
      in the lung after ultrasonically nebulized distilled water inhalation and
      inhibition of histamine-induced lethality in these animals suggests participation
      of mast cells in the phenomenon and could be helpful in understanding the
      mechanisms of hyperreactivity during helminth parasite infections.

PMID- 15973508
TI  - Fursultiamine, a vitamin B1 derivative, enhances chondroprotective effects of
      glucosamine hydrochloride and chondroitin sulfate in rabbit experimental
      osteoarthritis.
AB  - OBJECT AND DESIGN: The therapeutic effect of glucosamine hydrochloride (GH) and
      chondroitin sulfate (CS) in combination with fursultiamine, a vitamin B1
      derivative, on the development of cartilage lesions was investigated in an animal
      model of osteoarthritis (OA). METHODS: The OA model was created by partial medial
      meniscectomy of the right knee joint (day 0). The rabbits were placed into three
      experimental groups: operated (OA) rabbits that received placebo treatment, OA
      rabbits that received GH (1000 mg/kg) + CS (800 mg/kg), and OA rabbits that
      received GH + CS + fursultiamine (100 mg/kg). Each treatment was initiated on day
      3 and continued for 8 weeks. Macroscopic and histologic analyses were performed
      on the cartilage. The level of MMP-1 in OA cartilage chondrocytes was evaluated
      by immunohistochemistry. RESULTS: Only the group receiving combined treatment
      with GH + CS + fursultiamine showed a significant reduction in the severity of
      macroscopic and histologic lesions on tibial plateau, which is the weight bearing
      cartilage surface of the tibia, compared with placebo-treated OA rabbits. This
      treatment group also revealed a small, but significant, decrease in the body
      weight gain of the rabbits. In cartilage from placebo-treated OA rabbits, a
      significantly higher percentage of chondrocytes in superficial layer stained
      positive for MMP-1 compared with unoperated control. Rabbits treated with the GH
      + CS + fursultiamine revealed a significant reduction in the level of MMP-1.
      CONCLUSION: These results suggest that the chondroprotective effect of GH + CS is
      enhanced by the addition of fursultiamine in experimental OA. This effect was
      associated with a reduction in the level of MMP-1, which are known to play an
      important role in the pathophysiology of OA lesions.

PMID- 15973509
TI  - Effect of H1- and H2-receptor antagonists on the hemodynamic changes induced by
      the intravenous administration of ketamine in sevoflurane-anesthetized cats.
AB  - OBJECTIVE: The anesthetic ketamine has been reported to cause both an increase of
      the plasma histamine concentration, notably in cats, and a cardiovascular
      depression. The latter has been described in humans and in other species. However
      the relevance of the histamine fluctuation for the ketamine-induced hemodynamic
      changes has not been determined. SUBJECTS AND TREATMENT: We studied the
      contribution of histamine to the hemodynamic effects induced by IV ketamine (7
      mg/kg) in 12 sevoflurane anesthetized cats, of which half had been pre-treated
      with combined H(1)- and H(2) -receptor antagonists. METHODS: The mean arterial
      pressure (MAP) and the heart rate (HR) from both untreated (group C) and pre
      treated (group AH) cats were recorded before and after the ketamine
      administration. The plasma histamine concentration was also measured. RESULTS:
      Plasma histamine fluctuations in the control and the antihistamine-treated group
      followed a similar pattern (no statistical differences); an initial rise that
      peaked 2 min after ketamine injection (from 0.63 +/- 0.11 ng/ml to 2.22 +/- 0.69
      ng/ml in the C group, and from 0.71 +/- 0.10 ng/ml to 1.09 +/- 0.28 ng/ml in the
      AH group) followed by an immediate decrease in plasma concentrations. As for the
      hemodynamic variables under analysis, in the control group ketamine
      administration was followed by an early 30.3 +/- 8.1% reduction (p < 0.005) in
      the MAP with no associated changes in the HR. In the antihistamine pre-treated
      group, ketamine caused a further decrease of the MAP (41.7 +/- 2.3%), and a
      significant (p < 0.01) 11.6 +/- 2.9% reduction of the HR. CONCLUSION: Ketamine in
      anesthetized cats triggers histamine release and induces cardiovascular
      depression. The depression is more pronounced under the blockade of histamine
      activity through histamine receptor antagonists.

PMID- 15973510
TI  - Nitric oxide prevents the bacterial translocation and inhibits the systemic
      inflammatory response produced by implantation of a vascular prosthesis followed
      by Zymosan A.
AB  - OBJECTIVE AND DESIGN: To evaluate the beneficial effects of exogenous NO and its
      levels of action in a model of SIRS/Bacterial Translocation (BT) induced by two
      sequential insults. MATERIAL OR SUBJECTS: Eighty-six Wistar rats were submitted
      to different treatments and their tissue and blood samples were accessed at the
      end of the experiment. TREATMENT: Nitric Oxide was compared to Gentamicin as the
      tested guideline for our study. METHODS: Dacron graft implantation (first insult)
      and subsequent administration of Zymosan A((R)) (second insult) were performed in
      Wistar rats. The animals were divided into 6 groups: I) No manipulation (BASAL:
      ); II) Laparotomy (L) + mineral oil (SHAM: ); III) L + Graft-Zymosan (GZ)
      (CONTROL: ); IV) L + GZ + Antibiotic (A) (ASSAY: I); V) L + GZ + NO (ASSAY: II)
      and VI) L + GZ + A + NO (ASSAY: III). Determinations: Survival, Bacterial
      Translocation, myeloperoxidase (MPO), Cytokines (TNF-alpha, IL-1beta, IFN-gamma),
      Oxygen Free Radical (OFR) SOA and detoxifying enzymes (SOD, Superoxide Dismutase,
      CAT, Catalase and GPX, Glutathione Peroxidase), Cell Adhesion Molecules, CAMs
      (ICAM-1, VCAM-1 and PECAM-1) and Nuclear Transcription Factor, NFkappaB. RESULTS:
      The model established induced a mortality rate of 20% and generated BT in all
      samples. It also significantly increased all variables, with P < 0.001 for MPO
      and all Cytokines; P < 0.01 for all OFR, and P < 0.05 for CAMs and for NFkappaB.
      Treatment with A reduced mortality to 0%, significantly decreased BT, MPO,
      Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFkappaB. NO, either
      alone or associated, reduced mortality to 0% and abolished BT, significantly
      decreasing nearly all the variables studied (P < 0.001 for MPO and all Cytokines;
      P < 0.01 for OFR, and P < 0.05 for CAMs and for NFkappaB). CONCLUSIONS: The
      exogenous administration of NO before the two sequential insults prevented BT and
      controlled SIRS peripherally and at both cellular and transcriptional level in a
      lasting manner. In contrast, antibiotic treatment only exerted its action at
      peripheral level. The association of both treatments did not provide any
      important advantages.

PMID- 15973511
TI  - Unexpected high prevalence of hepatitis B and HIV infections in Malian medical
      students.

PMID- 15973512
TI  - Serial repositioning of a Gunther tulip retrievable inferior vena cava filter in
      a pediatric patient.
AB  - We report an 11-year-old boy who required inferior vena cava (IVC) filtration for
      a prolonged period of time. A retrievable IVC filter was placed and repositioned
      three times, providing a total of 60 days of IVC filtration. The filter was
      removed when his risk of pulmonary embolus had decreased substantially. This is a
      relatively uncommon practice in the pediatric population. The technique is
      presented, and the available literature is reviewed.

PMID- 15973513
TI  - Pancreatic lipomatosis in an infant with cystic fibrosis.

PMID- 15973514
TI  - Kidney development in the first year of life in small-for-gestational-age preterm
      infants.
AB  - BACKGROUND: Small-for-gestational-age (SGA) infants have been reported to have a
      significantly reduced number of nephrons that could be a risk factor for
      development of hypertension later in life. OBJECTIVE: To evaluate kidney size
      prospectively in relation to other anthropometric parameters during the first
      year of life in SGA babies. MATERIALS AND METHODS: The babies in the study were
      31-36 weeks' gestational age (GA) at birth and were matched with control preterm
      infants of similar GA, but appropriate for gestational age (AGA). The SGA infants
      were further classified as symmetrical and asymmetrical according to the
      anthropometric parameters. RESULTS: The total number of measurements in
      symmetrical SGA preterm infants was 324, in asymmetrical SGA preterm infants 295,
      and in AGA infants 536. In symmetrical SGA preterm infants (31-36 weeks' GA) mean
      kidney length (+/- SD) of 56+/-4 mm was significantly different from the controls
      (58.9+/-4.6 mm) up to 6 months' chronological age (P < 0.05). In the asymmetrical
      SGA preterm infants, mean kidney length (45.3+/-4.0 mm) was significantly
      different from the controls (48.2+/-4.4 mm) up to 40 weeks' corrected age. At 1
      year chronological age, all preterm infants (symmetrical and asymmetrical SGA and
      AGA) had similar mean kidney length (61.6+/-4.6, 62.8+/-4.3, and 62.3+/-4.0 mm,
      respectively). The ratio of kidney length to crown-to-heel length was similar in
      all preterm groups. CONCLUSIONS: Kidney length in preterm SGA infants
      (symmetrical and asymmetrical) follows closely the other auxological parameters
      during the first year of life.

PMID- 15973515
TI  - Multi-modality evaluation of the abnormalities of the aortic arches in children:
      techniques and imaging spectrum with emphasis on MRI.
AB  - The failure of embryonic vascular arches to fuse and regress in the usual manner
      during the formation of the aortic arch, pulmonary arteries and ductus arteriosus
      can cause a wide spectrum of vascular congenital abnormalities of the aortic arch
      and its branches. These abnormal vascular structures may cause variable
      compression of the trachea and/or oesophagus with symptoms ranging from none to
      severe stridor, dyspnoea, dysphagia and cyanosis. Diagnosis and possible
      treatment of affected patients require multiple imaging modalities. In the
      majority of cases, the underlying malformation can be detected by chest
      radiography and barium oesophagography, visualizing the location of the aortic
      arch and the presence of anomalous compressions of the trachea and/or oesophagus.
      However, in most cases the exact configuration of the vascular abnormality cannot
      be fully defined with conventional radiology alone. MRI is fundamental for
      evaluation of the thoracic vessels. Not only is it non-invasive, but it can also
      provide large-field-of-view images in any number of planes with three-dimensional
      reconstruction, adding valuable information about exact vascular configuration,
      tracheobronchial compression and brachiocephalic vessel branching. The aim of
      this review is to describe the imaging findings in children affected with special
      emphasis on MRI.

PMID- 15973516
TI  - Plasmodium falciparum heat shock protein 70 is able to suppress the
      thermosensitivity of an Escherichia coli DnaK mutant strain.
AB  - Heat shock protein 70 (Hsp 70) and heat shock protein 40 (Hsp 40) are molecular
      chaperones that ensure that the proteins of the cell are properly folded and
      functional under both normal and stressful conditions. The malaria parasite
      Plasmodium falciparum is known to overproduce a heat shock protein 70 (PfHsp 70)
      in response to thermal stress; however, the in vivo function of this protein
      still needs to be explored. Using in vivo complementation assays, we found that
      PfHsp 70 was able to suppress the thermosensitivity of an Escherichia coli dnaK
      756 strain, but not that of the corresponding deletion strain (DeltadnaK 52) or
      dnaK 103 strain, which produces a truncated DnaK. Constructs were generated that
      encoded the ATPase domain of PfHsp 70 fused to the substrate-binding domain (SBD)
      of E. coli DnaK (referred to as PfK), and the ATPase domain of E. coli DnaK
      coupled to the SBD of PfHsp 70 (KPf). PfK was unable to suppress the
      thermosensitivity of any of the E. coli strains. In contrast, KPf was able to
      suppress the thermosensitivity in the E. coli dnaK 756 strain. We also identified
      two key amino acid residues (V 401 and Q 402) in the linker region between the
      ATPase domain and SBD that are essential for the in vivo function of PfHsp 70.
      This is the first example of an Hsp70 from a eukaryotic parasite that can
      suppress thermosensitivity in a prokaryotic system. In addition, our results also
      suggest that interdomain communication is critical for the function of the PfHsp
      70 and PfHsp 70-DnaK chimeras. We discuss the implications of these data for the
      mechanism of action of the Hsp70-Hsp 40 chaperone machinery.

PMID- 15973517
TI  - Functional analysis of the BIN 2 genes of cotton.
AB  - Brassinosteroids (BR) promote the elongation of cotton fibers and may be a factor
      in determining their final length. To begin to understand the role of BR-mediated
      responses in the development of cotton fibers we have characterized the BIN 2
      genes of cotton. BIN 2 is a member of the shaggy-like protein kinase family that
      has been identified as a negative regulator of BR signaling in Arabidopsis.
      Sequence analyses indicate that the tetraploid cotton genome includes four genes
      with strong sequence similarity to BIN 2. These genes fall into two distinct
      subclasses based on sequence and expression patterns. Sequence comparisons with
      corresponding genes from cotton species that have the diploid A and D genomes,
      respectively, shows that each pair of genes comprises homeologs derived from the
      A and D sub-genomes. Transgenic Arabidopsis plants that express these cotton BIN
      2 cDNAs show reduced growth and similar phenotypes to the semi-dominant bin 2
      mutant plants. These results indicate that the cotton BIN 2 genes encode
      functional BIN 2 isoforms that can inhibit BR signaling. Further analyses of the
      function of BIN 2 genes and their possible roles in determining fiber yield and
      quality are underway.

PMID- 15973518
TI  - [Laparoscopic stomach bypass surgery].
AB  - Obesity is rapidly becoming a major medical problem in the developed world.
      Surgery is the only treatment with proven long-term efficiency for morbid
      obesity. We claim this surgery should be done by laparoscopy, because it is less
      invasive and morbidity is relatively low in obese patients, who are by definition
      fragile. Jejunojejunostomy can be performed by different techniques: side-to-side
      semimechanical, side-to-side entirely mechanical, end-to-side hand-sewn, and side
      to-side hand-sewn. Gastrojejunostomy can be performed by different techniques:
      circular mechanical anastomosis with the anvil inserted through the mouth,
      gastrostomy, linear mechanical anastomosis, or hand-sewn anastomosis. We report
      our technique of laparoscopic gastric bypass with different possibilities for the
      two anastomoses.

PMID- 15973519
TI  - Parenteral glutamine increases serum heat shock protein 70 in critically ill
      patients.
AB  - OBJECTIVE: Heat shock protein 70 (HSP-70) is protective against cellular and
      tissue injury. Increased serum HSP-70 levels are associated with decreased
      mortality in trauma patients. Glutamine (Gln) administration increases serum and
      tissue HSP-70 expression in experimental models of sepsis. Gln has been safely
      administered to critically ill patients and can improve clinical outcomes, but
      the effect of Gln administration on HSP-70 expression in humans is unknown. We
      examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP
      70 levels in critically ill patients. DESIGN AND SETTING: Randomized, controlled,
      double-blind study in surgical intensive care units (SICU) in a university
      hospital. PATIENTS: 29 patients admitted to the SICU and requiring PN for more
      than 7 days. INTERVENTIONS: Patients received either Gln-PN (containing alanyl
      glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN)
      that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were
      measured at enrollment and at 7 days. Clinical outcome measures were also
      determined. RESULTS: HSP-70 concentrations were unchanged in control-PN subjects
      from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated
      significantly higher (3.7-fold) serum HSP-70 concentrations than control
      subjects. In Gln-PN patients there was a significant correlation between
      increases in HSP-70 levels over baseline and decrease in ICU length of stay.
      CONCLUSIONS: Gln-PN significantly increases serum HSP-70 in critically ill
      patients. The magnitude of HSP-70 enhancement in Gln-treated patients was
      correlated with improved clinical outcomes. These data indicate the need for
      larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression
      in critical illness and relationship to clinical outcomes.

PMID- 15973520
TI  - Hemodynamic variables related to outcome in septic shock.
AB  - OBJECTIVE: To assess the impact of hemodynamic variables on the outcome of
      critically ill patients in septic shock and to identify the optimal threshold
      values related to outcome with special reference to continuously monitored mean
      arterial pressure (MAP) and mixed venous oxygen saturation (SvO2). DESIGN AND
      SETTING: Retrospective cohort study in a university hospital intensive care unit
      (ICU). PATIENTS: All consecutive 111 patients with septic shock treated in our
      ICU between 1 Jan. 1999 and 30 Jan. 2002. MEASUREMENTS AND RESULTS: The data on
      the hemodynamic and respiratory monitoring and circulation-related laboratory
      tests over the first 48 h of treatment in the ICU were collected from the
      clinical data management system. Data from 6 h and 48 h were analyzed separately.
      The 30-day mortality rate was 33% (36 of 111). Univariate analysis and forward
      stepwise logistic regression analysis were performed using the 30-day mortality
      as the primary endpoint. Mean MAP and lactate on arrival during 6 h, while mean
      MAP, the area of SvO2 under 70%, and mean CVP during 48 h were independently
      associated with mortality. MAP level of 65 mmHg and SvO2 of 70% had the highest
      areas under receiver characteristics curves. CONCLUSIONS: MAP, SvO2, CVP, and
      initial lactate were independently associated with mortality in septic shock,
      with threshold values supporting those published in recent guidelines.

PMID- 15973522
TI  - Inhaled nitric oxide therapy in adults--opinions and evidence.

PMID- 15973523
TI  - Colonic stricture secondary to hemolytic uremic syndrome caused by Escherichia
      coli O-157.
AB  - Shiga toxin-producing Escherichia coli (E. coli) is known to be one of the main
      causes of hemolytic uremic syndrome (HUS). Of the secondary complications of HUS,
      colonic stricture is relatively rare. We herein report on a Japanese girl that
      demonstrated sigmoid colon stricture secondary to HUS caused by an infection of
      E. coli O-157. Severe HUS occurred after the E. coli O-157 infection, so
      hemodialysis was performed due to renal failure. However, 1 month after recovery
      from HUS, abdominal symptoms occurred. A contrast study in the colon revealed a
      sigmoid colon stricture. The stricture was operatively resected. Thereafter, her
      postoperative course was uneventful. We also review the occurrence of this
      complication secondary to HUS in the literature.

PMID- 15973521
TI  - Inhaled nitric oxide therapy in adults: European expert recommendations.
AB  - BACKGROUND: Inhaled nitric oxide (iNO) has been used for treatment of acute
      respiratory failure and pulmonary hypertension since 1991 in adult patients in
      the perioperative setting and in critical care. METHODS: This contribution
      assesses evidence for the use of iNO in this population as presented to a expert
      group jointly organised by the European Society of Intensive Care Medicine and
      the European Association of Cardiothoracic Anaesthesiologists. CONCLUSIONS:
      Expert recommendations on the use of iNO in adults were agreed on following
      presentation of the evidence at the expert meeting held in June 2004.

PMID- 15973524
TI  - Acute renal failure, associated with non-steroidal anti-inflammatory drugs in
      healthy children.
AB  - Seven patients aged 13 to 17.5 years developed acute renal failure after
      treatment with a variety of non-steroidal anti-inflammatory drugs (NSAID):
      naproxen, diclofenac, ibuprofen, dipyrone and paracetamol. Six of the patients
      used more than one kind of NSAID. None of the patients had previous history of
      renal disease or concomitant treatment with other drugs. The time interval
      between NSAID administration to the emergence of symptoms ranged from 1 to 4
      days. The most common presenting symptoms were flank pain (4 patients), abdominal
      pain (3 patients) and vomiting (3 patients). All patients had normal urine
      output. Microscopic hematuria and proteinuria were found in 5 patients and
      leukocyturia in 2. Serum creatinine ranged from 1.3 to 8.3 mg% at presentation.
      Kidney biopsy was performed in 3 patients and showed findings consistent with
      mild interstitial inflammation in 1 patient, and normal renal tissue in 2. All
      patients were treated with intravenous fluids, 1 received corticosteroids. Renal
      function completely normalized in all patients within 7 to 16 days.

PMID- 15973525
TI  - Indirect voiding urosonography for detecting vesicoureteral reflux in children.
AB  - The purpose of our prospective study was to determine the value of indirect
      voiding urosonography without the use of contrast-media and without filling of
      the bladder through a catheter (IVUS) for detection of vesicoureteral reflux
      (VUR) in children, compared with echo-enhanced voiding urosonography (VUS). Among
      57 children (45 girls and 12 boys, aged 2.7 to 12.0 years) admitted for echo
      enhanced VUS either as part of routine evaluation after urinary tract infection
      (UTI) or follow-up of a previously detected VUR, IVUS was also successfully
      performed in 47 children. The results were considered positive when there was any
      increase in pelvis size and/or ureter lumen width during voiding. The overall
      sensitivity of IVUS in the detection of VUR was 49%, specificity 75%. The most
      accurate results were obtained with VUR grade III, where IVUS correctly detected
      6 out of 7 cases, a sensitivity of 86%. The average increase of AP pelvis
      diameter during voiding was highly significant only in uretero-renal units with
      VUR grade III. Considering the obstacles in conducting the investigation and its
      relatively low overall sensitivity and specificity, it seems that IVUS is not
      sufficiently reliable to replace echo-enhanced VUS.

PMID- 15973526
TI  - The effect of phototherapy on urinary calcium excretion in newborns.

PMID- 15973527
TI  - Management of nocturnal enuresis in Greek children.
AB  - Our experiences of managing nocturnal enuresis in Greek children at our
      Outpatient Clinics of Pediatric Urology are described. Between March 2001 and
      October 2003, 142 children with primary nocturnal enuresis (93 boys and 49
      girls), aged 7-18 years old (mean: 9.0+/-0.5) were included in this prospective
      study. Initially, behavioral conditioning therapy, using a body-worn urinary
      alarm, was instructed in all cases. If no improvement was recorded, 40 microg of
      intranasal desmopressin was administered, initially for three months. If
      urodynamic studies demonstrated pure detrusor instability, anticholinergics (5 mg
      oxybutinine or 2 mg tolterodine) were given instead. Combination medication
      (desmopressin and anticholinergics) was administered for coexisting diurnal
      enuresis, which was present in 8 children. Among the 142 children the overall
      response rate was 51.41%. Successful response was recorded in 16 children
      practicing conditioning behavioral therapy, in 47 receiving desmopressin (with or
      without anticholinergics), and in 10 children receiving only anticholinergics.
      During the follow-up period (mean: 6.2 months), no serious side effect was
      recorded. The use of desmopressin, and anticholinergics in specific subgroups,
      was found to be effective and safe for the management of nocturnal enuresis in
      children.

PMID- 15973528
TI  - A familial case of multicystic dysplastic kidney.
AB  - A familial case of multicystic dysplastic kidney (MCDK) is described. The proband
      is a one-year-old boy with left MCDK, and his father was also revealed to have
      unilateral MCDK. The mother had two abortions; the second pregnancy was
      terminated because of bilateral MCDK of the fetus (Potter anomaly). The two
      patients and the aborted male fetus did not have any malformations except for
      MCDK. Thus in this family MCDK occurs as an isolated phenomenon in three
      individuals within two generations, presumably as a result of autosomal dominant
      inheritance.

PMID- 15973529
TI  - Resolution of medullary nephrocalcinosis in children with metabolic bone
      disorders.
AB  - Ultrasonographic resolution of nephrocalcinosis (NC) has been reported in
      children with furosemide-induced NC, but not in other entities. We report the
      cases of four children with metabolic bone disease, two with hypophosphatasia and
      two with X-linked hypophosphatemic rickets, in whom we observed resolution of
      renal calcifications. At the time of ultrasonographic resolution of NC, 3 of the
      patients were on anticalciuric diuretics, and all 4 had normal urinalysis, serum
      creatinine and electrolyte profiles, as well as estimated creatinine clearance.
      In 3 of the children, evidence of mild tubular dysfunction was found. It thus
      seems that in some children with bone and mineral disorders who develop NC,
      ultrasonographic resolution of the renal calcifications can be seen; however,
      mild tubular dysfunction may remain and require follow-up. Further studies are
      suggested to explore the possible role of anticalciuric diuretics in promoting
      the resolution of NC.

PMID- 15973530
TI  - Renal damage in refluxing and non-refluxing siblings of index children with
      vesicoureteral reflux.

PMID- 15973531
TI  - Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study
      using 99mTc DMSA renal scintigraphy.
AB  - The aim of this study was to determine the prevalence of renal scarring in a
      group of Kuwaiti Arab children with their first documented acute pyelonephritis
      (APN). Eighty-two Kuwaiti Arab children (10 males and 72 females) who had
      abnormal (99m)Tc DMSA renal scan findings of acute pyelonephritis were
      prospectively studied with the same imaging modality 6 months after treatment to
      identify those who developed renal scarring. A micturition cystourethrogram
      (MCUG) was performed for all of the children 1 month after diagnosis. Children
      were divided into 3 age groups (<2 years, 2-5 years and above 5 years). The
      follow-up DMSA renal scans 6 months after diagnosis revealed normalization of
      renal changes in 56% (46 patients), much improvement with residual renal
      abnormality in 6% (5 patients), and persistent parenchymal defects in 38% (31
      patients). Vesicoureteric reflux (VUR) was found in 32% of children (26/82) and
      the majority were between grade I and III. Thirteen of those with VUR (50%)
      developed renal scars on follow-up. Fifty-three percent of the scarred kidneys
      (19/36) were drained by non-refluxing ureters. In this study, children older than
      2 years had less VUR yet were more susceptible to APN and to the development of
      renal scars. Girls were more prone to developing APN and renal scarring than
      boys. This work shows that APN is a serious cause for renal scarring in our
      patients, particularly if associated with other risk factors such as recurrent
      infections and the female sex.

PMID- 15973532
TI  - Dextran dextrinase and dextran of Gluconobacter oxydans.
AB  - Certain strains of Gluconobacter oxydans have been known since the 1940s to
      produce the enzyme dextran dextrinase (DDase; EC2.4.1.2)-a transglucosidase
      converting maltodextrins into (oligo)dextran. The enzyme catalyses the transfer
      of an alpha1,4 linked glucosyl unit from a donor to an acceptor molecule, forming
      an alpha1,6 linkage: consecutive glucosyl transfers result in the formation of
      high molecular weight dextran from maltodextrins. In the early 1990s, the group
      of K. Yamamoto in Japan revived research on DDase, focussing on the purification
      and characterisation of the intracellular DDase produced by G. oxydans ATCC
      11894. More recently, this was taken further by Y. Suzuki and coworkers, who
      investigated the properties and kinetics of the extracellular DDase formed by the
      same strain. Our group further elaborated on fermentation processes to optimise
      DDase production and dextran formation, DDase characterisation and its use as a
      biocatalyst, and the physiological link between intracellular and extracellular
      DDase. Here, we present a condensed overview of the current scientific status and
      the application potential of G. oxydans DDase and its products, (oligo)dextrans.
      The production of DDase as well as of dextran is first described via optimised
      fermentation processes. Specific assays for measuring DDase activity are also
      outlined. The general characteristics, substrate specificity, and mode of action
      of DDase as a transglucosidase are described in detail. Two forms of DDase are
      produced by G. oxydans depending on nutritional fermentation conditions: an
      intracellular and an extracellular form. The relationship between the two enzyme
      forms is also discussed. Furthermore, applications of DDase, e.g. production of
      (oligo)dextran, transglucosylated products and speciality oligosaccharides, are
      summarized.

PMID- 15973533
TI  - The appropriateness of swab cultures for the release of human allograft tissue.
AB  - Surgeries utilizing human allograft tissues have increased dramatically in recent
      years. With this increase has come a greater reliance on the use of swab
      culturing to assess allograft tissues for microbial contamination prior to
      distribution. In contrast to the typical industrial microbiological uses for
      swabs, the tissue banking industry has relied on swab cultures as a sterility
      release method for allograft tissues. It has been reported in the literature that
      swabs have limitations, both in sensitivity and reproducibility, so their
      suitability as a final sterility release method was evaluated in this study. Two
      different swab-culturing systems were evaluated (COPAN, EZ Culturette) using
      human allograft tissues spiked with low levels of multiple bacterial and fungal
      microorganisms. The average microbial recoveries for all challenge microorganisms
      for each tissue type and each swab system were calculated. Percent recoveries for
      each challenge microorganism were also calculated and reported. The results
      indicated that both swab systems exhibited low and highly variable recoveries
      from the seeded allograft tissues. Further analysis indicated there was no
      statistical difference ( proportional, variant=0.05) between the two swab
      systems. It is the recommendation of the authors that swab culturing not be used
      to assess relatively low levels of microbial contamination on allografts.
      Instead, alternative validated microbial detection methods with improved
      sensitivity and reproducibility should be employed and validated for this
      critical task.

PMID- 15973534
TI  - Risk mitigation of genetically modified bacteria and plants designed for
      bioremediation.
AB  - While the possible advantages of bioremediation and phytoremediation, by both
      recombinant microbes and plants, have been extensively reviewed, the biosafety
      concerns have been less extensively treated. This article reviews the possible
      risks associated with the use of recombinant bacteria and plants for
      bioremediation, with particular emphasis on ways in which molecular genetics
      could contribute to risk mitigation. For example, genetic techniques exist that
      permit the site-specific excision of unnecessary DNA, so that only the transgenes
      of interest remain. Other mechanisms exist whereby the recombinant plants or
      bacteria contain conditional suicide genes that may be activated under certain
      conditions. These methods act to prevent the spread and survival of the
      transgenic bacteria or plants in the environment, and to prevent horizontal gene
      flow to wild or cultivated relatives. Ways in which these genetic technologies
      may be applied to risk mitigation in bioremediation and phytoremediation are
      discussed.

PMID- 15973535
TI  - Brain MR diffusion tensor imaging and fibre tracking to differentiate between two
      diffuse axonal injuries.
AB  - We report here two cases of diffuse axonal injury (DAI) studied by MR diffusion
      tensor imaging (DTI) and fibre tracking (FT) focused on the corpus callosum. In
      one case, DTI and FT pattern matched the diagnosis of broken white matter tracts.
      In the other case there was a discrepancy between DTI and FT data that showed
      unaltered white matter tracts with the presence of intra-cellular oedema. These
      data suggested that DTI and FT are able to differentiate between traumatic
      cytotoxic oedema and broken fibres in the case of DAI.

PMID- 15973537
TI  - Cognitive impairment after traumatic brain injury: a functional magnetic
      resonance imaging study using the Stroop task.
AB  - The anterior cingulate cortex (ACC) plays a key role in cognition, motor
      function, and emotion processing. However, little is known about how traumatic
      brain injury (TBI) affects the ACC system. Our purpose was to compare, by
      functional magnetic resonance imaging (fMRI) studies, the patterns of cortical
      activation in patients with cognitive impairment after TBI and those of normal
      subjects. Cortical activation maps of 11 right-handed healthy control subjects
      and five TBI patients with cognitive impairment were recorded in response to a
      Stroop task during a block-designed fMRI experiment. Statistical parametric
      mapping (SPM99) was used for individual subjects and group analysis. In TBI
      patients and controls, cortical activation, found in similar regions of the
      frontal, occipital, and parietal lobes, resembled patterns of activation
      documented in previous neuroimaging studies of the Stroop task in healthy
      controls. However, the TBI patients showed a relative decrease in ACC activity
      compared with the controls. Cognitive impairment in TBI patients seems to be
      associated with alterations in functional cerebral activity, especially less
      activation of the ACC. These changes are probably the result of destruction of
      neural networks after diffuse axonal injury and may reflect cortical
      disinhibition attributable to disconnection or compensation for an inefficient
      cognitive process.

PMID- 15973536
TI  - Brain metabolite changes on proton magnetic resonance spectroscopy in children
      with poorly controlled type 1 diabetes mellitus.
AB  - The metabolite changes in the brains of children with poorly controlled type 1
      diabetes mellitus (DM) were investigated by proton magnetic resonance
      spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers
      underwent single-voxel MRS (TE: 136). The duration of disease, medication,
      presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in
      the patients were noted. Voxels were placed in the pons, left basal ganglion
      (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate
      (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average
      HbA1c level was 11.9 +/- 3.4 (8.2-19.4). The average number of keto-acidosis
      episodes was 1.9 +/- 2.2 (0-9) and the average number of daily insulin injections
      was 2.8 +/- 0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons
      and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects.
      No significant correlation was observed between the number of hypoglycaemia
      episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS
      in the brain of poorly controlled type 1 DM children. These metabolic changes, in
      particular in the pons region, include a decrease in NAA, indicating neuronal
      loss or functional impairment, and likely explanations for a decrease in Cho may
      be dynamic changes in membrane lipids and/or decreased membrane turnover.

PMID- 15973538
TI  - Multiaxial mechanical behavior of the porcine anterior lens capsule.
AB  - The biomechanics of the lens capsule of the eye is important both in physiologic
      processes such as accommodation and clinical treatments such as cataract surgery.
      Although the lens capsule experiences multiaxial stresses in vivo, there have
      been no measurements of its multiaxial properties or possible regional
      heterogeneities. Rather all prior mechanical data have come from 1-D pressure
      volume or uniaxial force-length tests. Here, we report a new experimental
      approach to study in situ the regional, multiaxial mechanical behavior of the
      lens capsule. Moreover, we report multiaxial data suggesting that the porcine
      anterior lens capsule exhibits a typical nonlinear pseudo-elastic behavior over
      finite strains, that the in situ state is pre-stressed multi-axially, and that
      the meridional and circumferential directions are principal directions of strain,
      which is nearly equi-biaxial at the pole but less so towards the equator. Such
      data are fundamental to much needed constitutive formulations.

PMID- 15973539
TI  - Use of tissue Doppler and its comparison with other conventional Doppler
      techniques in the assessment of diastolic functions in patients with active
      rheumatoid arthritis.
AB  - OBJECTIVE: This study aims to assess left ventricular diastolic functions with
      tissue Doppler imaging (TDI), which is a new technique, and to compare it with
      conventional Doppler echocardiography techniques in patients with active
      rheumatoid arthritis (RA). METHODS: Fifty-two patients with active RA and 47
      healthy persons were included in this study. All patients and the control group
      were evaluated by M-mod, two-dimensional, conventional Doppler echocardiography
      and TDI. RESULTS: Left ventricular early diastolic (E)/late diastolic (A) flow
      velocity (E/A ratio) was found to be lower in patients with RA than in the
      control group (p<0.001). Mitral annular early diastolic (E(m))/late diastolic
      (A(m)) velocity(E(m)/A(m) ratio) was found to decrease in RA patients compared
      with the control group (p<0.001). E/E(m) ratio was higher in patients with RA
      than in the control group (p<0.001). CONCLUSION: Left ventricular diastolic
      functions were impaired in patients with RA. We have concluded that TDI alone, or
      together with conventional Doppler echocardiography, is useful for the evaluation
      of diastolic functions in RA patients.

PMID- 15973540
TI  - Imaging features of spinal osteoid osteoma with emphasis on MRI findings.
AB  - A retrospective evaluation of the imaging of 13 patients with a diagnosis of
      osteoid osteoma (OO) of the spine was undertaken. Available imaging included
      radiographs (n=10), computed tomography (CT) (n=13), bone scintigraphy (n=5) and
      magnetic resonance imaging (MRI) (n=13). MRI features evaluated were pattern of
      neural arch and vertebral body oedema and the presence of an identifiable nidus.
      MRI features were correlated with other available imaging. There were seven males
      and six females with an age range of 8-59 years. On radiographs, scoliosis was
      present in ten and a sclerotic pedicle in nine patients. Focal increased uptake
      on bone scintigraphy consistent with OO was seen in all five patients where
      scintigraphy was available. On CT, a nidus was identified in all patients and
      reactive sclerosis was seen in 12. MRI demonstrated the nidus in eight patients
      and unilateral neural arch oedema with anterior extension to involve the
      ipsilateral posterolateral vertebral body in 11. When MRI is performed in the
      evaluation of back pain, the presence of unilateral neural arch oedema extending
      to involve the posterolateral vertebral body raises the possibility of spinal OO
      and should prompt CT to confirm the presence of a nidus.

PMID- 15973541
TI  - Individual and regional variations of phospho-tau species in progressive
      supranuclear palsy.
AB  - The purpose of this study was to learn about possible variations in phospho-tau
      profiles in terms of case-to-case differences, regional modifications and
      diversification of tau phosphorylation sites in five PSP cases with moderate to
      severe frontosubcortical dysfunction. Gel electrophoresis of sarkosyl-insoluble
      fractions and Western blotting with five anti-tau phospho-specific antibodies
      directed to phosphorylation sites Thr181, Ser202, Ser214, Ser396 and Ser422 were
      used to study four brain regions including frontal cortex, area 8, subcortical
      white matter of the frontal lobe, caudate/putamen: striatum, and basis pontis:
      pons. Although two bands of 66 and 62 kDa were observed in almost every region in
      each case, the intensity of the bands depends on the anti-tau phospho-specific
      antibody. More importantly, bands of 72, 50/55 and 37 kDa were commonly found in
      PSP brains, whereas other bands of about 60, 42, 33 and 29 kDa were irregularly
      observed. The pattern of bands differed slightly from one case to another and
      from one region to another. Moreover, the phospho-tau profile differed depending
      on the anti-tau phospho-specific antibody used. These data suggest that several
      species of tau are variably phosphorylated at a given time in a given region (and
      probably in a given cell), and that tau aggregates are composed of several
      phosphorylated truncated or cleaved tau molecules, in addition to phosphorylated
      complete tau isoforms.

PMID- 15973542
TI  - 14-3-3 proteins in Lewy body-like hyaline inclusions in a patient with familial
      amyotrophic lateral sclerosis with a two-base pair deletion in the Cu/Zn
      superoxide dismutase (SOD1) gene.

PMID- 15973543
TI  - The unfolded protein response is activated in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is, at the neuropathological level, 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) that may protect the cell against the
      toxic buildup of misfolded proteins. In this study we investigated the activation
      of the UPR in AD. Protein levels of BiP/GRP78, a molecular chaperone which is up
      regulated during the UPR, was found to be increased in AD temporal cortex and
      hippocampus as determined by Western blot analysis. At the immunohistochemical
      level intensified staining of BiP/GRP78 was observed in AD, which did not co
      localize with AT8-positive neurofibrillary tangles. In addition, we performed
      immunohistochemistry for phosphorylated (activated) pancreatic ER kinase (p
      PERK), an ER kinase which is activated during the UPR. p-PERK was observed in
      neurons in AD patients, but not in non-demented control cases and did not co
      localize with AT8-positive tangles. Overall, these data show that the UPR is
      activated in AD, and the increased occurrence of BiP/GRP78 and p-PERK in
      cytologically normal-appearing neurons suggest a role for the UPR early in AD
      neurodegeneration. Although the initial participation of the UPR in AD
      pathogenesis might be neuroprotective, sustained activation of the UPR in AD
      might initiate or mediate neurodegeneration.

PMID- 15973544
TI  - Spindle cell oncocytoma of the adenohypophysis: report of two cases.

PMID- 15973545
TI  - Liver resection or cryotherapy for colorectal liver metastases: a prospective
      case control study.
AB  - BACKGROUND AND AIMS: While there is promising survival data for cryosurgery of
      colorectal liver metastases, local recurrence following cryoablation remains a
      problem. We aimed to compare morbidity and mortality, as well as the recurrence
      pattern and survival after liver resection and cryotherapy (alone or in
      combination with resection) for liver metastases. PATIENTS AND METHODS: Between
      1996 and 2002, 168 patients underwent liver resection alone and 55 patients had
      cryotherapy (25 in combination with liver resection) for colorectal liver
      metastases. The patient, tumour and operative details were recorded prospectively
      and the two patient groups were compared regarding morbidity, survival and
      recurrence. RESULTS: More patients had a prior liver resection, liver metastases
      were smaller and less frequently synchronous, morbidity was significantly lower
      and hepatic recurrence was significantly more frequent in the cryotherapy group.
      Five-year survival rates following resection and cryotherapy were comparable (23
      and 26% respectively), while overall and hepatic recurrence-free survival was
      inferior following cryotherapy. CONCLUSION: Cryotherapy is a valuable treatment
      option for some patients with non-resectable colorectal liver metastases. While
      survival is comparable to that after resection, higher hepatic recurrence rates
      following cryotherapy should caution against the use of cryotherapy for
      resectable disease until the results of randomized controlled trials are
      available.

PMID- 15973546
TI  - Increased augmentation of central blood pressure is associated with increases in
      carotid intima-media thickness in type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is associated with a two- to seven-fold increase
      in cardiovascular morbidity and mortality. The aim of this study was to determine
      the relationships between intima-media thickness (IMT), an established marker of
      atherosclerosis, large artery function and other determinants of cardiovascular
      risk in type 2 diabetic patients. METHODS: We studied 228 type 2 diabetic
      patients (75 women, aged 62+/-2 years [mean+/-SEM]). Carotid IMT was bilaterally
      measured using ultrasound technology. Applanation tonometry and pulse wave
      analysis were used to measure aortic systolic and diastolic blood pressures,
      central pressure augmentation (AG) and the augmentation index (AIx), a measure of
      systemic arterial stiffness. Conventional cardiovascular risk factors (lipids,
      HbA(1)c, smoking and diabetes duration) were also assessed. RESULTS: Women had
      higher AG and AIx (p<0.0001), despite comparable systolic BP and heart rate in
      women and men. In women, AG (r=0.39, p<0.001), age (r=0.32, p<0.01), brachial
      systolic BP (r=0.34, p<0.01) and aortic systolic BP (r=0.34, p<0.01) correlated
      with IMT. In men, age (r=0.41, p<0.001), diabetes duration (r=0.25, p<0.01), AG
      (r=0.22, p<0.01), aortic systolic BP (r=0.21, p<0.01), brachial systolic BP
      (r=0.21, p<0.01) and body weight (r=0.16, p<0.05) correlated with IMT. In
      multiple linear regression analyses, AG and aortic systolic BP, but not brachial
      systolic BP, were age-independent determinants of IMT in men and women. In all
      patients, increased AG (adjusted for sex, age and heart rate) correlated with
      longer duration of diabetes, urinary albumin excretion and IMT.
      CONCLUSIONS/INTERPRETATION: Measures of central systolic pressure correlate with
      carotid IMT, independently of age and other risk markers.

PMID- 15973547
TI  - Intercontinental chemical variation in the invasive ant Wasmannia auropunctata
      (Roger) (Hymenoptera Formicidae): a key to the invasive success of a tramp
      species.
AB  - Unicoloniality emerges as a feature that characterizes successful invasive
      species. Its underlying mechanism is reduced intraspecific aggression while
      keeping interspecific competitiveness. To that effect, we present here a
      comparative behavioural and chemical study of the invasive ant Wasmannia
      auropunctata in parts of its native and introduced ranges. We tested the
      hypothesis that introduced populations (New Caledonia archipelago) have reduced
      intraspecific aggression relative to native populations (e.g., Ilheus area,
      Brazil) and that this correlates with reduced variability in cuticular
      hydrocarbons (CHCs). As predicted, there was high intraspecific aggression in the
      Brazilian populations, but no intraspecific aggression among the New Caledonian
      populations. However, New Caledonian worker W. auropunctata remained highly
      aggressive towards ants of other invasive species. The chemical data corresponded
      with the behaviour. While CHCs of ants from the regions of Brazil diverged, the
      profiles of ants from various localities in New Caledonia showed high uniformity.
      We suggest that in New Caledonia W. auropunctata appears to behave as a single
      supercolony, whereas in its native range it acts as a multicolonial species. The
      uniformity of recognition cues in the New Caledonia ants may reflect a process
      whereby recognition alleles became fixed in the population, but may also be the
      consequence of a single introduction event and subsequent aggressive invasion of
      the ecosystem. Chemical uniformity coupled with low intraspecific but high
      interspecific aggression, lend credence to the latter hypothesis.

PMID- 15973549
TI  - [Ureteral injuries. Diagnostic and treatment algorithm].
AB  - The most common cause of iatrogenic injuries to the ureter (75%) is a
      gynecological or surgical pelvic procedure. The diagnosis of ureteral injuries is
      delayed in 66% (after days or weeks). Lack of hematuria is an unreliable sign to
      exclude injury, since 30% of all ureteral injuries do not even demonstrate
      microscopic hematuria or classic clinical symptoms and signs. In view of this,
      the diagnosis must be one of suspicion and further evaluations are mandatory in
      all cases of penetrating or blunt abdominal injuries. The most accurate
      diagnostic tools are CT scan with delayed excretory images and retrograde
      ureterography, which can also be used to guide stent placement. Low-grade
      injuries can be sufficiently treated with urinary diversion by PCN drainage or
      endoscopic ureteric stenting. The treatment of high-grade injuries depends on the
      localization and extent of the damage. The principles of repair include
      debridement, spatulation, lack of tension, stenting, postoperative drainage, and
      a watertight anastomosis with fine nonreactive absorbable suture. A delay in
      diagnosis is the most important factor contributing to the morbidity of ureteric
      injuries, and early treatment can reduce the complication rate to below 5%.

PMID- 15973550
TI  - [The "Pisse-Prophet" or the "English fortune-teller from urine". A critical book
      on uroscopy bei Thomas Brian].
AB  - In the middle ages, uroscopy was the main nosological principle in medicine. It
      lead to quackery. One of the critics of uroscopy, who demanded a medicine mainly
      oriented on the patient, was Thomas Brian in 1637.

PMID- 15973548
TI  - [Genetic and molecular biological aspects of the bladder exstrophy-epispadias
      complex (BEEC)].
AB  - The bladder exstrophy and epispadias complex (BEEC) is an anterior midline defect
      with variable expression involving the infraumbilical abdominal wall including
      the pelvis, urinary tract, and external genitalia. The incidence varies with
      regard to ethnical background, sex, and phenotypic expression, and an incidence
      of 1:20,000 to 1:80,000 has been observed in the middle European population. No
      gene defect has been attributed to BEEC thus far and chromosomal aberrations or
      genetic syndromes associated with BEEC have only rarely been reported. According
      to epidemiological data, a complex genetic as well as a multifactorial mode of
      inheritance could underlie BEEC. However, no single teratogenic agent or
      environmental factor has been identified, which could play a dominant role in the
      expression of the BEEC.A risk of recurrence of 0.5-3% has been described in
      families with one affected subject. These values correspond to an increased
      recurrence risk estimated to be as high as 200- to 800-fold when compared to the
      common population. Due to the paucity of affected sib pairs and suitable
      multiplex families, conventional linkage analysis to identify candidate genes
      causally related with BEEC appears to be unfeasible. Large association studies
      and consecutive linkage disequilibrium mapping should therefore lead to the
      identification of candidate genes. Also new methods including matrix-based
      comparative genomic hybridization (CGH) are promising and have successfully been
      used in the past (e.g., CHARGE association). Moreover, the low incidence of the
      BEEC requires close cooperation between clinicians in the operative and
      nonoperative specialties as well as geneticists for successful gene search.

PMID- 15973551
TI  - [Generalized purpura as dermatologic manifestation of thrombcytopenia].
AB  - A 72-year old patient was initially misdiagnosed with allergic vasculitis. He
      rapidly developed petechiae and mucosal bleeding. There were no other abnormal
      physical findings and the patient was otherwise in good physical condition. There
      was no history of trauma or infectious disease. The patient's complete blood
      count showed a marked thrombocytopenia of 2000/nl. A bone marrow biopsy confirmed
      the initial diagnosis of idiopathic thrombocytopenic purpura (ITP). The number of
      thrombocytes increased and the skin lesions resolved shortly after the patient
      was put on oral prednisone. This case emphasizes the importance of dermatologic
      symptoms in diagnosing severe systemic disease.

PMID- 15973552
TI  - [Modelling critical information measurement traumatic surgery decisions.
      "Sequential Information Appraisal Module (SIAM)"].
AB  - We studied the quality and quantity of information leading to the emergency
      physician's decision to intubate severely injured patients on scene. Our aim was
      to assess intuitive aspects of clinical decision making. The experiment involved
      three different phases, with a fourth phase examining retest reliability. We used
      trauma register data from 98 patients. Based on various parameters (physiological
      data, injury assessment on scene, definite injury pattern), three emergency
      surgeons were requested to decide on the need for endotracheal intubation.We
      applied multivariate logistic regression to estimate the likelihood of intubation
      given certain clinical characteristics or combinations of characteristics. We
      compared the participants' decisions to those made by "true" emergency physicians
      on scene. Kappa statistics marked inter-observer agreement beyond chance. The
      Glasgow Coma Scale (GCS) was the only single predictor of intubation in the ideal
      test setting (area under the receiver operating characteristics curve [AUC] >98%)
      as well as on scene (AUC 0.85, 95% confidence interval 0.78-0.92). There was no
      difference between the discriminatory features of the single item GCS and complex
      multivariate models that included anatomically defined injury scales (best model
      in phase 2: AUC 0.96, best model in phase 3: AUC 0.98). Overall inter-observer
      agreement was substantial in phase 1 (kappa=0.74), fair to moderate in phase 2
      (kappa=0.49) and slight to fair in phase 3 (kappa=0.23). Retest reliability
      ranged from 51% to 91%. Doctors give priority to only a small part of the
      information available in deciding for or against a particular intervention.

PMID- 15973553
TI  - American society of clinical oncology--41st annual meeting.

PMID- 15973554
TI  - American society of clinical oncology--41st annual meeting. Immunology.

PMID- 15973555
TI  - American Society of Clinical Oncology--41st annual meeting. Drug highlights I.

PMID- 15973556
TI  - American Society of Clinical Oncology--41st annual meeting. Drug highlights II.

PMID- 15973557
TI  - Digestive Disease Week 2005. Drug highlights I.

PMID- 15973558
TI  - Digestive Disease Week 2005. Drug highlights II.

PMID- 15973559
TI  - Antimicrobial Agents And Resistance--Fifth International Symposium.
AB  - The Fifth International Symposium on Antimicrobial Agents and Resistance (ISAAR)
      provided a comprehensive review of current developments, with emphasis on new
      antimicrobial agents in development, novel vaccines, and public health concerns
      about respiratory virus pandemics and bioterrorism. This report describes new
      antimicrobial agents in clinical development or those recently approved, as well
      as progress in development of antibacterial agents with novel targets. Other
      agents under development include antimicrobial peptides, bactericidal
      permeability-increasing proteins, self-assembling peptide nanotubes, and
      antisense nucleotides.

PMID- 15973560
TI  - Antimicrobial Agents and Resistance--Fifth International Symposium. Antifungal
      agents and novel vaccines.

PMID- 15973561
TI  - PharmaDiscovery 2005. Kinases in drug discovery.

PMID- 15973562
TI  - European Atherosclerosis Society--75th congress.
AB  - The 75th European Atherosclerosis Society congress, held in Prague, Czech
      Republic, at the end of April 2005, was a large, well-attended meeting of
      international scientists with specialist interest in the field of cardiovascular
      diseases. Few new drugs emerged at the meeting as treatment options for
      cardiovascular diseases, however, many interesting basic and clinical data were
      presented that will eventually lead to better and improved cardiovascular
      therapies. This report is focused on recent advances in statin therapy (the TNT
      study and the role of pharmacogenetics in predicting individual response to
      statin therapy); clinical evidence of the combination therapy of ezetimibe +
      simvastatin; phase III clinical data on the selective cannabinoid type I receptor
      blocker rimonabant (sanofi-aventis); the role of peroxisome proliferator
      activated receptor a agonists in the treatment of the metabolic syndrome; and the
      rationale for, and the recent advances in high-density lipoprotein-targeted
      therapy.

PMID- 15973563
TI  - SOZO--a Euro-Japanese biotechnology conference.

PMID- 15973564
TI  - Noordwijkerhout-Camerino--15th Symposium. Trends in drug research.

PMID- 15973565
TI  - The impact of pharmacophore modeling in drug design.
AB  - With the reliable use of computer simulations in scientific research, it is
      possible to achieve significant increases in productivity as well as a reduction
      in research costs compared with experimental approaches. For example, computer
      simulation can substantially enchance productivity by focusing the scientist to
      better, more informed choices, while also driving the 'fail-early' concept to
      result in a significant reduction in cost. Pharmacophore modeling is a reliable
      computer-aided design tool used in the discovery of new classes of compounds for
      a given therapeutic category. This commentary will briefly review the benefits
      and applications of this technology in drug discovery and design, and will also
      highlight its historical evolution. The two most commonly used approaches for
      pharmacophore model development will be discussed, and several examples of how
      this technology was successfully applied to identify new potent leads will be
      provided. The article concludes with a brief outline of the controversial issue
      of patentability of pharmacophore models.

PMID- 15973566
TI  - Use of high-content analysis for compound screening and target selection.
AB  - High-content analysis (HCA) has rapidly established itself as a core technology
      in drug discovery for secondary cell-based screening. When combined with our
      knowledge of genetics, HCA can provide a powerful tool for target validation, but
      excitingly, HCA may also enable the increased use of cellular assays in high
      throughput screening for novel drug leads.

PMID- 15973567
TI  - Gimatecan (sigma-tau industrie farmaceutiche riunite/novartis).
AB  - Sigma-Tau Industrie Farmaceutiche Riunite SpA and Novartis AG are developing oral
      gimatecan, a camptothecin derivative, for the potential treatment of tumors,
      including glioblastoma.

PMID- 15973568
TI  - NO-enhanced drug cocktails.

PMID- 15973569
TI  - American Society of Clinical Oncology - 37th annual meeting. 12-15 May 2001, San
      Francisco, CA, USA.

PMID- 15973570
TI  - American Society of Clinical Oncology - 37th Annual Meeting. Highlights of oral
      and poster sessions. 12-15 May 2001, San Francisco, CA, USA.

PMID- 15973571
TI  - American Society of Clinical Oncology - 37th Annual Meeting. Small-molecule
      therapeutics. 12-15 May 2001, San Francisco, CA, USA.

PMID- 15973572
TI  - American Society of Clinical Oncology - 37th Annual Meeting. Novel antitumor
      agents. 12-15 May 2001, San Francisco, CA, USA.

PMID- 15973573
TI  - American Society of Clinical Oncology - 37th Annual Meeting. Small molecule
      tyrosine kinase inhibitors. 12-15 May 2001, San Francisco, CA, USA.

PMID- 15973574
TI  - American Society of Clinical Oncology - 37th Annual Meeting. Ovarian cancer and
      new clinical therapeutics. 12-15 May 2001, San Francisco, CA, USA.

PMID- 15973575
TI  - American Society of Clinical Oncology - 37th Annual Meeting. Non-small cell lung
      cancer. 12-15 May 2001, San Francisco, CA, USA.

PMID- 15973576
TI  - Digestive disease week 2001. 20-23 May 2001, Atlanta, GA, USA.

PMID- 15973577
TI  - Digestive Disease Week 2001. Esophageal, gastric and intestinal motility, and
      functional disorders. 20-23 May 2001, Atlanta, GA, USA.

PMID- 15973578
TI  - Digestive Disease Week 2001. Novel therapeutic principles in inflammatory bowel
      disease. 20-23 May 2001, Atlanta, GA, USA.

PMID- 15973579
TI  - Digestive Disease Week 2001. Gastrointestinal motility. 20-23 May 2001, Atlanta,
      GA, USA.

PMID- 15973580
TI  - Digestive disease week 2001. American association for the study of liver
      diseases. 19-23 May 2001, Atlanta, GA, USA.
AB  - All aspects of hepatology were represented at this year's meeting of the American
      Association for the Study of Liver Diseases (AASLD), although the meeting was
      dominated by a proliferation of information in the arena of viral hepatitis. In
      an international multicenter study of over 1000 treatment-naive patients with
      hepatitis C virus (HCV) infection, sustained virological response was found in
      56% of patients who received PEGylated interferon (IFN) alpha-2a (Pegasys; F
      Hoffmann-La Roche) in combination with ribavirin (Virazole; ICN Pharmaceuticals),
      versus 45% in patients who received IFN alpha-2b and ribavirin therapy, and 30%
      of patients who received PEG. This is a significant improvement on currently
      licensed therapy and will define practice patterns for the next decade. In other
      areas, novel therapies such as silymarin for cholestatic liver disease, L-dT
      (Novirio Pharmaceuticals Inc), herbal therapy, combination therapies including
      amantadine and mycophenolate mofetil (Roche Holding) for viral hepatitis, and
      long-acting octreotide (Sandostatin LAR Depot; Novartis) for portal hypertension,
      were presented. This review represents the best of AASLD at DDW 2001.

PMID- 15973581
TI  - Digestive Disease Week 2001. New therapies and technologies. 19-23 May 2001,
      Atlanta, GA, USA.

PMID- 15973582
TI  - Digestive Disease Week 2001. COX-2 and gastrointestinal disease. 20-23 May 2001,
      Atlanta, GA, USA.

PMID- 15973583
TI  - American Urological Association - 96th Annual Meeting. 2-7 June 2001, Anaheim,
      CA, USA.

PMID- 15973584
TI  - American Society of Gene Therapy - Fourth Annual Meeting. 30 May-3 June 2001,
      Seattle, WA, USA.
AB  - The American Society of Gene Therapy (ASGT) was established in 1996 and has a
      current membership of more than 2400 members worldwide. The society was formed
      with the aim of exchanging information, to encourage research and promote
      education within the field of gene therapy, and this conference provided the
      ideal platform for the fostering of ideas and the exchange and dissemination of
      information related to the field. This report will focus on the clinical data
      presented and potentially novel gene therapies.

PMID- 15973585
TI  - American Society of Gene Therapy - Fourth Annual Meeting. Emerging technologies.
      30 May-3 June 2001, Seattle, WA, USA.

PMID- 15973586
TI  - American Society of Microbiology - 101st General Meeting. 20-24 May 2001,
      Orlando, FL, USA.
AB  - Sessions on prokaryotic genomics, bioinformatics, antibiotic resistance,
      intrinsic antibacterial resistance, and the identification of novel targets were
      the main highlights of this year's American Society Microbiology (ASM) meeting.
      In addition, updates on the status of antimicrobial developmental candidates and
      recently approved agents, were also discussed.

PMID- 15973587
TI  - American Society of Microbiology - 101st General Meeting. Vaccines and
      antifungals. 20-24 May 2001, Orlando, FL, USA.

PMID- 15973589
TI  - Vaccine Development and Immunotherapy in HIV - Second International Conference.
      22-25 May 2001, San Juan, Puerto Rico.

PMID- 15973588
TI  - American Society of Microbiology - 101st General Meeting. Resistance and new
      generation quinolones. 20-24 May 2001, Orlando, FL, USA.

PMID- 15973590
TI  - Neuropeptide Y receptor antagonists.
AB  - A review of the patent literature for neuropeptide Y (NPY) antagonists is
      presented for the period of January 2000 to March 2001. This review focuses on
      antagonists of the Y(1) and Y(5) receptor subtypes, which have been of primary
      interest as anti-obesity agents. In contrast to the Y(5) receptor, there have
      been only a limited number of new chemical entities claimed as antagonists at the
      Y(1) receptor. This may suggest either a greater interest in the Y(5) subtype as
      a target for therapeutic intervention or difficulty in finding small, potent, non
      peptide antagonists of the Y(1) receptor. Nevertheless, there are subnanomolar
      antagonists that are selective for both receptor subtypes available, which should
      prove to be useful in determining the roles of the Y(1) and Y(5) receptors in
      food intake, energy homeostasis, and other physiological functions.

PMID- 15973591
TI  - Pseudotyped retrovectors for tumor-specific delivery of toxic suicide genes.
AB  - Tumor-targeted gene transfer of the suicide gene, herpes simplex virus thymidine
      kinase (HSV-TK) is an extremely powerful biopharmaceutical approach for the
      treatment of cancer. However, no substantive clinical benefit has been reported
      since this concept was first developed more than a decade ago. This review
      summarizes the current status of human clinical trials employing viral-vector
      based delivery of HSV-TK as well as novel means being developed by which killing
      of tumor cells could be enhanced. In particular, we discuss of the use of VSV-G
      pseudotyped retrovectors in successfully achieving high tumor-restricted gene
      transfer efficiency in preclinical studies and the challenges still to be
      overcome to bring cancer gene therapy safely to the clinic.

PMID- 15973592
TI  - CBP-1011. InKine Pharmaceutical Co.
AB  - CBP-1011 (medroxyprogesterone acetate) is an immunosuppressant corticosteroid
      under development by InKine Pharmaceuticals (formerly CorBec Pharmaceuticals) for
      the potential treatment of a number of inflammatory conditions. Phase III trials
      are underway in the US for the treatment of idiopathic thrombocytopenic purpura
      [234943]. By December 2000, it had completed phase II trials for the treatment of
      inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative
      colitis (UC) [393219]. In March 2001, the FDA designated CBP-1011 an Orphan Drug
      for the treatment of thrombocytopenic pupura [400935]. In June 2000, InKine
      reported that a US patent (subsequently identified as US-06068983, entitled
      'Methods of stimulating phagocytosis' and assigned to University of Pennsylvania)
      had been issued to Alan D Schreiber MD, Chairman of InKine's Scientific Advisory
      Board. The patent describes methods of increasing Fc receptors on white blood
      cells or macrophages, as well as inducing Fc receptors in cells that do not
      normally possess them, such as lung and liver cells [370990]. In April 2001, the
      University of Pennsylvania (inventor again Alan D Schreiber) claimed the use of
      medroxyprogesterone acetate for treating IBD, CD, UC, food allergies, hemorrhoids
      and psoriasis in WO-00122959, entitled 'Method of treating inflammatory
      conditions with progesterone or progesterone analogs'.

PMID- 15973593
TI  - Parecoxib. Pharmacia corp.
AB  - Pharmacia (formerly Monsanto) is developing parecoxib, an injectable COX-2
      inhibitor, for the management of post-surgical acute pain [287279], [313957]. By
      January 1999, the compound was in phase III trials for this indication [312280].
      In October 2000, Pharmacia submitted an NDA for parecoxib sodium for the
      management of acute pain to the FDA. The company anticipated a 12-month review of
      the NDA [387654] but received a 'not approvable' letter in July 2001, indicating
      there were deficiencies in the filing; at this time, Pharmacia anticipated
      refiling before the end of 2002 [415668]. Under a license agreement with
      Pharmacia Corp, parecoxib (designated YM-177) is being developed in Japan by
      Yamanouchi [392030]. Prior to the FDA ruling, in June 2000, the company
      anticipated that the compound would be launched by 2001 [370466]. In March 2000,
      Merrill Lynch predicted that parecoxib would be filed in the third quarter of
      2000 [361969], [382577]. By May 2001, the analysts revised their predictions to
      launch in 2002 [411811].

PMID- 15973594
TI  - Differentiation of prostate cancer from normal prostate tissue in an animal
      model: conventional MRI and dynamic contrast-enhanced MRI.
AB  - PURPOSE: To differentiate orthotopically implanted prostate cancer from normal
      prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced
      dynamic MRI in the rat model. MATERIAL AND METHODS: Tumors were induced in 15
      rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells.
      MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted
      spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the
      contrast medium based dynamic study. The interstitial leakage volume, normalized
      permeability and the permeability surface area product of tumor and healthy
      prostate were determined quantitatively using a pharmacokinetic model. The
      results were confirmed by histologic examination. RESULTS: Axial T2-weighted TSE
      images depicted low-intensity areas suspicious for tumor in all 15 animals. The
      mean tumor volume was 46.5 mm(3). In the dynamic study, the suspicious areas in
      all animals displayed faster and more pronounced signal enhancement than
      surrounding prostate tissue. The interstitial volume and the permeability surface
      area product of the tumors increased significantly by 420 % (p < 0.001) and 424 %
      (p < 0.001), respectively, compared to normal prostate tissue, while no
      significant difference was seen for normalized permeability alone. CONCLUSION:
      The results of the present study demonstrate that quantitative analysis of
      contrast-enhanced dynamic MRI data enables differentiation of small, slowly
      growing orthotopic prostate cancer from normal prostate tissue in the rat model.

PMID- 15973595
TI  - Diffusion-weighted echo-planar MRI: a valuable tool for differentiating primary
      parotid gland tumors?
AB  - PURPOSE: To investigate the feasibility of using diffusion-weighted (DW) echo
      planar imaging (EPI) for differentiating primary parotid gland tumors. MATERIAL
      AND METHODS: Fifty consecutive patients with a suspected primary tumor of the
      parotid gland were examined with a DW EPI sequence (TR 1,500 msec, TE 77 msec,
      field of view 250 x 250 mm, pixel size 2.10 x 1.95 mm, section thickness 5 mm).
      The b factors used were 0, 500, and 1,000 sec/mm (2). Apparent diffusion
      coefficient (ADC) maps were digitally transferred to MRIcro (Chris Rorden,
      University of Nottingham, Great Britain) and evaluated with a manually placed
      irregular region of interest (ROI) containing the entire tumor. Additionally, the
      contralateral, non affected parotid gland was measured and a circular ROI
      containing 100 - 200 pixels was placed in the cerebrospinal fluid (CSF) next to
      the spinal cord in every patient. For comparison of the results, the two-tailed
      Student's t test was used, based on the median ADC values for each patient, and a
      p-value <.05 was determined to indicate statistical significance. RESULTS: In 45
      patients, a primary neoplasm of the parotid gland could be histologically
      verified. For the non-affected parotid glands of all 45 evaluated patients, the
      mean ADC value was 1.14 x 10 ( - 3) mm (2)/sec +/- 0.12 x 10 ( - 3) mm (2)/sec
      (mean +/- standard deviation). Seven different entities of parotid gland tumors
      were histologically discriminated. Pleomorphic adenomas (2.14 x 10 ( - 3) mm
      (2)/sec +/- 0.11 x 10 ( - 3) mm (2)/sec), Warthin tumors (0.85 x 10 ( - 3) mm
      (2)/sec +/- 0.1 x 10 ( - 3) mm (2)/sec), and mucoepidermoid carcinomas (1.04 x 10
      ( - 3) mm (2)/sec +/- 0.3 x 10 ( - 3) mm (2)/sec) showed statistically
      significant different ADC values in comparison to all other evaluated tumors (p
      .001), and also among each other (p <.001). Additionally, ADC values presented by
      lipomas were statistically significant compared to all other entities (p <.001 to
      .015). Among all other [corrected] primary malignant parotid gland tumors, no
      statistically significant ADC values could be observed (p .18 to 1). CONCLUSION:
      Diffusion-weighted echo-planar MRI seems to be a valuable tool for
      differentiating benign from malignant primary parotid gland tumors.

PMID- 15973596
TI  - [Surgery for congestive heart failure--the role of computed tomography in the pre
      and postoperative diagnostic evaluation].
AB  - The treatment of advanced, drug resistant congestive heart failure gains in
      importance in the field of cardiac surgery. Cardiac imaging for preoperative
      assessment and follow-up focuses on the determination of ventricular volumes and
      function as well as on the detection of postoperative complications. Computed
      tomography (CT) is highly accurate irrespective of the individual patient's
      anatomic situation, has a low examiner dependence and short examination time,
      does not require an arterial vascular access and can be performed in patients
      with metal implants. CT is the modality of choice in the follow-up of heart
      transplants to detect extracardiac and cardiac complications including coronary
      calcifications as an early sign of transplant vasculopathy. In addition, CT
      visualizes the elements of mechanical assist devices and can identify their
      possible local cardiac and mediastinal complications. CT can detect
      fibrolipomatous involution of the mobilized muscle flap in dynamic
      cardiomyoplasty and can depict fibrous reactions along the epicardial mesh
      implant in passive cardiac containment. Further indications include assessment of
      typical local postoperative complications, such as intrathoracic infection and
      mediastinal bleeding, intracardiac thrombus formation or pericardial effusion. CT
      is routinely used for evaluating bypass patency but is limited in assessing
      associated valve defects since it does not visualize flow.

PMID- 15973597
TI  - [Digital X-ray mammography: comparison of the image quality achievable with a wet
      laser imager, a dry infrared laser imager and a dry laser imager using direct
      thermography].
AB  - PURPOSE: To compare the image quality of digital X-ray mammographies obtained
      with wet imagers with that of standard dry imaging technology. MATERIAL AND
      METHODS: Beginning 03/08/2003, 200 X-ray mammographies with a digital fullfield
      mammography system (Lorad Selenia, Lorad/Hologic) were prospectively and
      consecutively documented with a wet laser imager (Scopix LR 5200, Agfa), a dry
      infrared laser imager (DryView 8610, Kodak) and a dry imager using the principle
      of direct thermography (Drystar 4500M, Agfa, N = 166). One X-ray exposure was
      systematically chosen from each examination and was presented in an anonymous and
      randomized form to three radiologists who evaluated the films using a structured
      questionnaire. RESULTS: The visualization of normal anatomic structures was
      considered being good to excellent for all imagers with the mean assessments 1.0 
      2.4 for the Drystar 4500M, 1.0 - 2.1 for the DryView 8610 and 1.1 - 2.0 for the
      Scopix LR 5200. The mean assessments were 0.1 - 0.6 points lower in dense than in
      normal parenchyma, thus, the parenchymal density is the predominant factor for
      image quality. CONCLUSION: In view of the comparable image quality obtained with
      the different imagers used in the study, individual decisions to purchase a
      specific imager will be based on economics rather than on diagnostic points of
      view.

PMID- 15973598
TI  - [Partial breast irradiation for early breast cancer with favorable prognostic
      factors: 3-year results of the German-Austrian phase II-trial].
AB  - PURPOSE: To evaluate perioperative morbidity, toxicity and cosmetic outcome in
      patients treated with interstitial brachytherapy to the tumor bed as the sole
      radiation modality after breast conserving surgery. MATERIALS AND METHODS: From
      11/2000 to 11/2004, 240 women with early stage breast cancer participated in a
      protocol of tumor bed irradiation alone using pulsed dose rate (PDR) or high dose
      rate (HDR) interstitial multi-catheter implants (partial breast irradiation).
      Perioperative morbidity, acute and late toxicity as well as cosmetic outcome were
      assessed. Of the first 51 patients treated in this multicenter trial, we present
      interim findings after a median follow-up of 36 months. RESULTS: Perioperative
      Morbidity: Bacterial infection of the implant: 2 % (1/51). Acute toxicity:
      radiodermatitis Grade 1: 4 % (2/51). Late toxicity: breast pain Grade 1: 8 %
      (4/51), Grade 2: 2 % (1/51); dyspigmentation Grade 1: 8 % (4/51); fibrosis Grade
      1: 4 % (2/51), Grade 2: 8 % (4/51); telangiectasia Grade 1: 10 % (5/51), Grade 2:
      4 % (2/51). Cosmetic results: Excellent and good in 94 % (48/51) of the patients.
      CONCLUSION: This analysis indicates that accelerated partial breast irradiation
      with 192-iridium interstitial multicatheter PDR-/HDR-implants (partial breast
      irradiation) is feasible with low perioperative morbidity, low acute and mild
      late toxicity at a median follow-up of 36 months. The cosmetic result is not
      significantly affected.

PMID- 15973599
TI  - [High-resolution T1-weighted MR-lymphography of inguinal lymph nodes after
      interstitial application of Gadomer-17 in animal experiments].
AB  - PURPOSE: To evaluate the microstructural anatomy of inguinal lymph nodes in pigs
      after interstitial MR-lymphography with the dendritic contrast agent Gadomer-17.
      MATERIAL AND METHODS: High-resolution T1-weighted MR-lymphography was performed
      in inguinal lymph nodes of 10 domestic pigs (39 - 46 kg) after subcutaneous
      injection of 10 mumol/kg body weight Gadomer-17 in the hind legs of the animals.
      A 1.5T MR scanner and a ring-shaped surface coil were used. Two different high
      resolution gradient-echo sequences with additionally reconstructed maximum
      intensity projections were evaluated in a total of 20 lymph nodes. The high
      resolution MR-findings were correlated with the histologic sections of the
      excised inguinal lymph nodes. RESULTS: Coronal T1-weighted 3D gradient-echo
      images (TR = 20 msec, TE = 6.1 - 8.3 msec, FA = 20 degrees ) with a slice
      thickness of 1 mm, a field-of-view of 120 mm and a matrix size of 256 x 256
      (reconstructed to 1024 x 1024 voxels) yielding a reconstructed in-plane
      resolution of 117 x 117 microm (2) were best suited for the high-resolution MR
      lymphography of inguinal lymph nodes and enabled the differentiation of the
      hyperintense lymph node sinuses and hypointense lymphoid parenchyma of each lymph
      node (100 %). Even dilated lymphatic vessels evident in the histologic specimen
      were best demonstrated on the MIP images. CONCLUSION: High-resolution
      interstitial MR lymphography with Gadomer-17 allows the visualization of
      different tissue compartments of inguinal lymph nodes. This new technique is
      feasible on a routine 1.5T scanner and may offer potential for the detection of
      micrometastases in lymph nodes of cancer patients.

PMID- 15973600
TI  - [Comparison of homogenous strain-analysis with wall thickening for the MR
      tomographic assessment of regional myocardial function].
AB  - PURPOSE: To compare strain analysis and wall thickening (WT) analysis in
      differentiating the infarcted, adjacent, and remote zones in a rat model of
      myocardial infarction (MI). MATERIAL AND METHODS: Three normal (NL) and ten rats
      subjected to myocardial infarction were imaged on a 4.7T scanner. Gradient-echo
      and SPAMM-tagged cine images were acquired at three short axis levels of the left
      ventricle (LV). A homogenous strain analysis (principal strains lambda1 and
      lambda2, displacement D, angle beta) and a WT-analysis (mm- and %-thickening)
      were performed in all slices demonstrating MI. Regional function was compared
      between infarcted rats (infarcted, adjacent and remote zone) and corresponding
      regions in the NL rats. Additional segmental analysis was performed in the NL
      rats for the anterior, lateral, inferior and septal wall. RESULTS: In the NL
      rats, lambda (1) (greatest radial thickening) was greatest in the lateral and
      anterior wall. WT-analysis showed a pattern of function similar to lambda1,
      however, regional differences using WT-analysis were not significant. lambda (2)
      (greatest circumferential shortening) was most negative in the anterior wall. D
      was greatest in the lateral and inferior wall. The angle beta was radially
      directed in all segments. In the infarcted rats, both strain and WT-analyses
      revealed significant impairment in function in the infarcted and adjacent zones
      as compared to NL (p < 0.001). However, only the strain analysis (lambda1,
      lambda2, p < 0.001) detected significant remote myocardial dysfunction.
      Myocardial function differed significantly between the infarcted and adjacent and
      between the infarcted and remote regions. Strain analysis (lambda2, D, beta, p <
      0.001) also identified significant functional differences between the adjacent
      and remote zones, however, no statistically significant differences were found
      using WT-analysis. CONCLUSION: Strain analysis is superior to WT-analysis in
      detecting regional functional variations in NL rats and in discriminating
      function in the infarcted, adjacent and remote zones post MI.

PMID- 15973601
TI  - [Experimental testing of a new coil design for endoluminal MRI applied to the pig
      stomach].
AB  - PURPOSE: Experimental feasibility study of a new MR-Coil concept for enhanced
      visualization of the gastric wall. MATERIAL AND METHODS: The newly developed
      single-loop receiver coil for endoluminal imaging (Fraunhofer Institute, St.
      Ingbert, Germany) was evaluated in 4 explanted pig stomachs in a 1.5T MR unit
      (Siemens Symphony, Erlangen, Germany) with T1 w and T2 w MR sequences in three
      planes. The new coil consists of a foldable and self-expanding single loop coil
      (receiver coil) of a shape memory metal (nitinol). It was covered with a
      biocompatible material (silicone) to prevent direct contact of the wire with
      stomach tissue. The coil assumes a circular configuration with a diameter of 8 cm
      because of its memory metal properties. The flexible characteristics of the
      material used allow the passage through the instrument channel (13 mm diameter)
      of a specially designed MR-compatible endoscope. The purpose of our study was to
      assess feasibility of the coil design as a first step in developing a new
      endoluminal MRI-concept. Additionally the number and signal intensity of visible
      gastric wall layers were evaluated and findings were correlated with
      histopathological results of a pig stomach. RESULTS: The new coil concept was a
      feasible system in all 4 cases and showed good image quality for analysis. On T1
      w images, 3 layers were visible in all cases, and on T2 w images 4 different
      gastric wall layers were seen in 2 cases. Due to histopathological correlation,
      the different gastric wall layers were identified as follows: mucosa, submucosa
      and muscularis propria if three layers were depicted; in cases of 4 visible wall
      layers, serosa and subserosa could be detected additionally. For each gastric
      wall layer, a distinct signal intensity was found. CONCLUSION: The new MR coil
      concept for endoluminal imaging proved to be a feasible technique. Good
      differentiation of gastric wall layers in the pig stomach could be demonstrated.
      We have shown that endoscopic MR-imaging with our new coil concept is a valuable
      technique for the visualization of gastric wall layers. Due to this fact, follow
      up studies including assessing safety aspects are necessary to finally conduct an
      experimental-clinical study on in-vivo human gastric specimens to detect tumor
      growth and morphology within the gastric wall. Endoscopic MRI may have the
      potential in the future to overcome today's limitations of diagnostic imaging in
      gastric cancer.

PMID- 15973602
TI  - [Correlation of duplex sonographic stenosis grading by means of cross-sectional
      analysis and MR-tomographic blood volume flow quantification in unilateral
      stenosis of the internal carotid artery].
AB  - PURPOSE: Correlation of duplex ultrasonographic grading of unilateral internal
      carotid artery (ICA) stenosis and ICA blood volume flow (BVF) quantification.
      MATERIALS AND METHODS: Using a 2D cine phase-contrast MR technique, 62 patients
      with unilateral ICA stenosis at the level of the bifurcation between 50 % and 98
      % and 20 age-matched normal controls were examined. BVF was measured in the
      stenosed ICA. Ultrasonographic grading of stenoses was based on cross-sectional
      duplex sonography (color Doppler flow imaging [CDFI], real-time compound imaging)
      and compared to the changes in BVF in the stenosed ICA. RESULTS: There was no
      statistically significant difference in BVF in stenoses of the ICA up to 70 % and
      in normal controls. ICA stenoses greater 70 % began to be hemodynamically
      relevant. With increasing stenosis, a decrease in BVF in the ipsilateral ICA was
      determined with a high and linear correlation of r = - 0.83. Normal controls
      showed a BVF in an ICA of 247.0 +/- 32.0 ml/min, patients with 70 % stenosis a
      mean BVF of 225.3 +/- 32.2 ml/min (P = 0.4) without significant reduction,
      patients with 80 % stenosis a significant reduction of BVF to a mean flow of
      184.0 +/- 53.8 ml/min (P < 0.005), patients with 90 % stenosis a reduction of the
      mean BVF in the stenosed ICA to 84.6 +/- 41.9 ml/min (P < 0.0005) and patients
      with stenoses > 95 % a mean BVF of only 26.0 +/- 4.0 ml/min (P < 0.0005). In
      patients with unilateral ICA stenosis greater than 81 %, a significant decrease
      of BVF in the stenosed ICA was documented. CONCLUSION: Comparison of
      ultrasonographic grading of unilateral ICA stenosis and BVF determination in
      patients with ICA stenoses demonstrate a high correlation between increase in the
      stenosis and decrease in the ipsilateral blood flow beginning at 70 % stenosis.
      ICA stenoses greater than 80 % are significantly hemodynamically relevant.

PMID- 15973603
TI  - [Sensor-based detection of skull positioning for image-guided cranial navigation
      under free head mobility].
AB  - PURPOSE: Although computer- and image-guided surgical procedures are an
      improvement of frame-guided stereotaxy, many navigation systems still require
      rigid fixation of the patient's head throughout the operation. This study
      describes the clinical application of a technical modification that enables
      cranial navigation with "free head mobility" using CT and MR images as well as
      the calculated 3-D reconstruction models. MATERIAL AND METHODS: A sensor-based
      electromagnetic neuronavigation system was expanded to allow the localization and
      position monitoring of several sensors within an electromagnetic field. One of
      these sensors was attached to a dental splint as an additional reference (DRF =
      dynamic reference frame). Thus, it was possible to determine the position of the
      sensor-guiding surgical instruments and to record the slightest movement of the
      cranium as well. This information was then used to continuously adapt the
      position of the imaging plane and the resultant calculated 3-D reconstructions to
      the actual position of the cranium. RESULTS: The clinical application of the DRF
      was tested for different neurosurgical procedures. They included image-guided
      biopsies and endoscopic interventions using MRI data, transnasal accesses to the
      base of the skull using CT data and surgical removal of multilocular metastases
      using data from both imaging modalities. Intracranial target reference points as
      well as those on the skull were found with a high accuracy to the initial
      measurement position after arbitrary movement of the patient's head. Thus,
      navigation was also possible without rigid fixation of the head because of the
      continuous adaptation of the imaging data on the change in position of the
      patient's head. CONCLUSION: Based on these first test results, a high clinical
      potential for DRF application in cranial navigation is to be expected. The aim of
      DRF is to dispense with the rigid fixation of the patient's head. This increases
      the application scope of image-guided navigation procedures to include, for
      example, any bioptic or endoscopic intervention, in which rigid pin fixation of
      the cranium is not required or desired. For all other procedures, continuous
      position monitoring by DRF ensures automatic correction of imaging data with
      mechanical alteration of the head position.

PMID- 15973604
TI  - [Simplified production of multimedia based radiological learning objects using
      the flash format].
AB  - PURPOSE: Evaluation of the applicability of the Flash Format for the production
      of radiological learning objects used in an e-learning environment. MATERIAL AND
      METHODS: Five exemplary learning objects with different didactic purposes
      referring to radiological diagnostics are presented. They have been intended for
      the use within the multimedia, internet-based e-learning environment LaMedica.
      Interactive learning objects were composed using the Flash 5.0 software
      (Macromedia, San Francisco, USA) on the basis of digital CT and MR images,
      digitized conventional radiographs and different graphical elements prepared as
      TIFF files or in a vector graphics format. RESULTS: After a short phase of
      initial skill adaptation training, a radiologist author was soon able to create
      independently all learning objects. The import of different types of images and
      graphical elements was carried out without complications. Despite manifold design
      options, handling of the program is easy due to clear arrangement and structure,
      thus enabling the creation of simple as well as complex learning objects that
      provided a high degree of attractiveness and interaction. Data volume and
      bandwidth demand for online use was significantly reduced by the Flash Format
      compression without a substantial loss of visual quality. CONCLUSION: The
      universally compatible Flash Format offers an opportunity for the simple
      production of radiological learning objects that fulfill all relevant needs of
      modern internet based e-learning environments, such as interactivity, employment
      of multimedia and convertibility.

PMID- 15973605
TI  - [Teleradiology: economic research analysis of CT investigations in a small
      hospital].
AB  - PURPOSE: To evaluate, discuss and compare economic aspects of teleradiological
      applications in CT examinations in a small hospital. Scenario (1): CT examination
      by an extern institution including transport of a patient. Szenario (2): External
      consultation of an internal CT examination (teleradiology according to ROV).
      Scenario (3): Complete in-house radiology department. To evaluate economic
      aspects of teleradiology service providers. MATERIALS AND METHODS: Costs have
      been separated into fixed and variable costs in a model. Total costs of 500 CT
      examinations per year have been calculated for the three scenarios. A break-even
      analysis has been performed to determine the necessary/minimal number of CTs per
      year for economical advantages. The number of CT consultations for teleradiology
      service providers to make profit has been calculated. RESULTS: Scenario (1): This
      is the most cost-effective scenario for 500 CTs per year, but most time
      consuming. Beyond 548 CTs per year using a single slice CT and 965 CTs per year
      using a multislice CT the teleradiology scenario [scenario (2)] is most cost
      effective. Beyond 1065 CTs per year an in-house radiology department [scenario
      (3)] is economically reasonable. On the basis of 30 Euros per CT consultation a
      teleradiology service providing system will be profitable starting from 322 CT
      consultations per year. CONCLUSION: Teleradiology applications are economically
      reasonable in a wide range in small hospitals. CT teleradiology services can also
      be provided on a cost-effective basis at a reachable number of consultations.

PMID- 15973606
TI  - [The DEVIC disease: a rare differential diagnosis of disseminated
      encephalomyelitis].

PMID- 15973607
TI  - [Persistent left superior vena cava with drainage into the left atrium--a case
      report].

PMID- 15973608
TI  - [Embolisation in an acute, traumatic vascular injury of the medial meningeal
      artery ].

PMID- 15973609
TI  - [Pneumocystis pneumonia (PCP)--Pneumocystis carinii pneumonia (Syn. Pneumocystis
      jirovecii pneumonia)].

PMID- 15973610
TI  - [Perspective through the century--world and human images since the day of
      Roentgen].

PMID- 15973611
TI  - [Unclear tumors in the adnexal region--MRT: younger women with complex ultrasonic
      findings can profit].

PMID- 15973612
TI  - [Rectal carcinoma--MRT is better than endorectal sonography].

PMID- 15973613
TI  - [Fluoroscopy as a resource--radiological investigations of the lumbar spine].

PMID- 15973614
TI  - [Cost effectiveness--radiation-induced telangiectasia treated with the
      Hyfrecator].

PMID- 15973615
TI  - [MRT of the cervical musculature--proof of fat distribution in muscle tissue].

PMID- 15973616
TI  - [Multiple trauma--is the standard MDCT protocol sufficient for the evaluation of
      spinal cord injuries].

PMID- 15973617
TI  - [Rectal carcinoma--new MRT criteria improve lymph node staging].

PMID- 15973618
TI  - [Complications after vertebroplasty and kyphoplasty--cement emboli recognized on
      typical radiographic images].

PMID- 15973624
TI  - [Haemodynamics and diabetic retinopathy].
AB  - Diabetic retinopathy is the most common cause of blindness in adults in all
      industrialised countries. A much better pathophysiological understanding of the
      disease has been achieved during the last years. There is evidence that a
      functional deficit in haemodynamics proceeds the morphological changes of the
      retina. Modern technologies for measuring haemodynamic parameters and their
      correlation to pathophysiology in diabetic retinopathy are discussed. In the near
      future it will be possible to use these parameters as an early sign of worsening
      before morphological changes occur. Measurement of the therapeutic success, e.
      g., in laser coagulation would seem to be possible.

PMID- 15973625
TI  - [Electronic visual prostheses].
AB  - BACKGROUND: Currently, no treatment is available for progressive retinal
      dystrophies. The fabrication of an implantable visual prosthesis seems to be
      possible now as a result of advances in the fabrication of extremely small micro
      systems and their encapsulation in biocompatible materials. MATERIALS AND
      METHODS: The development of implantable visual prostheses is based on the
      fabrication of remotely controlled microelectrode arrays which have to be
      implanted in different target regions of the visual system. Prototypes of such
      systems have already been implanted in animal experiments and also in pilot
      trials in humans. RESULTS: Four concepts are pursued: 1. epiretinal implant --
      fixation onto the inner retinal surface; 2. subretinal implant -- implantation
      within the subretinal space; 3. optic nerve stimulator -- cuff electrode placed
      around the optic nerve; 4. cortical prosthesis -- implantation of surface
      electrodes in the region of the visual cortex. All these concepts have already
      been applied in pilot trials in humans. The results show some promising visual
      perception. CONCLUSIONS: The use of implantable electronic visual prostheses will
      become a possible option in the treatment of currently untreatable retinal
      dystrophies. Further basic research initiatives are necessary as well as further
      human trials to characterize the stimulation parameters and to improve the
      currently available devices.

PMID- 15973626
TI  - [Treatment of neovascular age-related macular degeneration with
      Ranibizumab/Lucentis].
AB  - Vascular endothelial growth factor (VEGF) is considered to play an essential role
      in the pathogenesis of age-related macular degeneration due to its vascular
      permeability-inducing and angiogenic properties. Ranibizumab, a small antibody
      fragment designed to competitively bind all VEGF isoforms, passes after
      intravitreal injection all retinal layers reaching the retinal pigment epithelium
      choroid complex. Experimental animal models showed the drug to be safe and
      effective. Subsequently, Phase I/II clinical trials conducted in patients with
      neovascular AMD demonstrated a good safety profile, and a significant functional
      benefit. Ranibizumab therapy repeated every four weeks for the treatment of
      neovascular AMD is currently in Phase III clinical trials. Combination therapy
      trials aiming for improved treatment durability and effectiveness are currently
      ongoing as well as new treatment strategies using intermittent, optical coherence
      tomography (OCT) guided therapy. Anti-VEGF therapy using Ranibizumab is a
      promising new treatment option for neovascular AMD.

PMID- 15973627
TI  - [Ocular side-effects associated with amiodarone therapy].
AB  - Amiodarone, one of the most effective anti-arrhythmic drugs, is also known for
      its ability to accumulate lipid-pharmakon complexes in the lysosomes of different
      tissues. In the eye the lysosomal storage leads to typical side-effects. Whorl
      like epithelial, reversible corneal inclusions occur in about 70 to 100 % of the
      patients on amiodarone therapy. Tiny lens opacities without visual impairment
      have been reported in 50 % of patients who had been treated with amiodarone. At
      present the most severe complication of amiodarone is optic neuropathy with an
      incidence of 1.3 to 1.8 %. The optic neuropathy, as the rule, is only reversible
      approximately in (1/2) of the patients after discontinuing the drug. The
      fundoscopic picture of amiodarone neuropathy is similar to classic AION. Retinal
      involvement has also been reported; however, a relationship with amiodarone has
      not been proven yet.

PMID- 15973628
TI  - [Results of phacoemulsification during the learning phase].
AB  - BACKGROUND: The subjective and objective results during the training phase of
      phacoemulsification using a 6 mm sclero-corneal tunnel incision at 12 h were
      evaluated. PATIENTS AND METHODS: In a prospective study we evaluated the first
      221 cases of phacoemulsification by a cataract surgeon during his training phase.
      Objective parameters which were analyzed included intraoperative complications,
      preoperative, early postoperative (p. o.) (1 - 13 days) and late p. o. (to the
      third month) assessment of refraction, visual acuity and corneal astigmatism.
      Calculation of the induced astigmatism was performed using the subtraction method
      and the vector analysis according to Jaffe. For evaluation of subjective results
      we used a questionnaire in the late p. o. phase. The questionnaire contained
      questions concerning satisfaction with the explanation of the surgical procedure,
      the medical personnel, the procedure itself and the result of the operation.
      RESULTS: During surgery, 6 posterior capsular ruptures (2.7 %) and 3 zonular
      dialyses (1.4 %) occurred. In 6 cases (2.7 %) an anterior vitrectomy was
      necessary, in two cases (0.9 %) an anterior-chamber lenses had to be implanted.
      Preoperatively, the average visual acuity was 0.5 +/- 0.14 (n = 221), the early
      p. o. visual acuity was 0.49 +/- 0.23 (n = 220) and the late p. o. visual acuity
      was 0.73 +/- 0.31 (n = 121). The average spheric equivalent was early p. o. 0.04
      D +/- 1.18 D (n = 208) and late p. o. 0.11 D +/- 1.08 D (n = 118). The difference
      to the planned refraction was early p. o. 0.68 D +/- 1.13 D, and late p. o. 1.39
      D +/- 1.18 D. The mean induced astigmatism early p. o. was 0.55 D +/- 0.97 D (n =
      166) and late p. o. 0.37 D +/- 0.87 D (n = 121) (subtraction method). Utilizing
      vector analysis for calculation of the induced astigmatism we obtained 1.43 D +/-
      0.86 D (n = 121) for the early p. o. situation and 1.22D +/- 0.88 D (n = 121) for
      the late p. o. situation, respectively. 80 % of the patients (n = 119) were
      satisfied with the results (highest rating), 3 % were unhappy (lowest rating).
      CONCLUSION: The results of this study reveal that phacoemulsification is a safe
      and satisfactory procedure for patient, even during the training phase of a
      cataract surgeon.

PMID- 15973629
TI  - [Mitomycin C in refractive corneal surface surgery with the excimer laser: first
      experience and review of the literature].
AB  - Haze formation with loss of corneal transparency and surface irregularities and
      myopic regression are the major complications after corneal refractive surface
      surgery. The use of mitomycin C (MMC) with its antibiotic and antineoplastic
      properties is intended to inhibit wound healing mechanisms leading to
      subepithelial fibrosis. We report the use of MMC to achieve visual rehabilitation
      in the re-treatment of 3 eyes of 2 patients following refractive corneal surgery.
      According to the literature, the local use of MMC 0.02 % for 2 minutes is safe
      and enables one to treat and prevent stromal haze and myopic regression and
      allows a reduction of the postoperative topical pharmacotherapy. Results are
      still limited due to small case numbers and short follow-up periods.

PMID- 15973630
TI  - [Clinicopathological characteristic of keratoglobus].
AB  - BACKGROUND: This study describes the clinical, topographical, pachymetrical, and
      histological features of a unique corneal disorder: keratoglobus. CASE REPORT:
      Ultrasound pachymetry proved that the structure of the cornea was evenly thinning
      towards the periphery. Histological examinations disclosed the absence of
      Bowman's membrane and the thinning of the stromal lamellae. CONCLUSION: On
      account of the thickness of the recipient's periphery, penetrating keratoplasty
      proved to be a reasonable surgical procedure in this case.

PMID- 15973631
TI  - [Surgical treatment of cyclodialysis].
AB  - PURPOSE: Cyclodialysis is a rare complication following blunt traumatic bulb
      injuries or surgical interventions. When treatment with cycloplegics or steroids
      is ineffective in attaching the ciliary body, cyclodialysis should be surgically
      treated. However, for reliable diagnosis and surgical therapy, an exact
      identification (size and extent) of the cyclodialysis cleft is imperative.
      Ultrasound biomicroscopy (UBM) provides the appropriate information. CASE REPORT:
      Four patients (19 to 65 years old, mean 45 years) with a detached ciliary body
      are described. Three patients had suffered an injury, and one patient presented
      with a prior trabeculotomy. The diagnosis was established with UBM. The location
      of the cyclodialysis cleft ranged between 2 and 3 o'clock (mean 2.4 o'clock). In
      spite of an intense treatment with cycloplegics and steroids no reattachment of
      the cyclodialysis took place. Therefore, a surgical intervention was performed.
      The span between the injury and trabeculotomy, respectively, and the
      cyclodialysis operation ranged from 3 to 30 months (mean 12 months). On average,
      visual acuity was increased from 0.3 preoperatively to 0.6 postoperatively, and
      the intraocular pressure was 6 mm Hg before and 15 mm Hg after operation.
      Symptoms preoperatively found without exception (choroidal detachment,
      papilledema "e vacuo", macular edema) had a complete recovery after operation.
      CONCLUSION: In cases where drug therapies are unsuccessful in attaching the
      ciliary body, an operative fixation is recommended. UBM is a very useful tool for
      making an exact diagnosis and defining the location of cyclodialysis as well as
      for follow-up of surgical treatment.

PMID- 15973632
TI  - [Friedrich Joseph Haas-- the holy doctor from Moscow].

PMID- 15973633
TI  - [The botanist and doctor Pietro Andrea Matthioli].
AB  - The physician Pietro Andrea Mattioli (1500 - 1577) is known for his Italian
      translation and commentary of the work of the Greek botanist Pedanios
      Dioscurides: "Di Pedacio Dioscoride Anazerbeo libri cinque ..." (first published
      in 1544). The physician broadened Dioscurides' studies by including new medicinal
      plants and numerous detailed woodcuts. In 1554 the fifth edition had already been
      published: "I Discorsi di M. Pietro Andrea Matthioli Sanese, Medico Cesareo ...
      Di Pedacio Dioscuride Anacarbeo della materia Medicinale ...". The book was also
      translated into Latin, French, Spanish, German and Bohemian. Matthioli describes
      plants, that can be used to treat eye-diseases.

PMID- 15973634
TI  - [Cost-utility analysis of relapsing-remitting multiple sclerosis treatment with
      azathioprine or interferon beta in Spain].
AB  - AIM: To carry out a cost-utility analysis of the treatment of relapsing-remitting
      multiple sclerosis (RRMS) with azathioprine (Imurel) or beta interferon (all,
      Avonex, Rebif and Betaferon). MATERIAL AND METHODS: Pharmacoeconomic Markov model
      comparing treatment options by simulating the life of a hypothetical cohort of
      women aged 30, from the societal perspective. The transition probabilities,
      utilities, resource utilisation and costs (direct and indirect) were obtained
      from Spanish sources and from bibliography. Univariant sensitivity analyses of
      the base case were performed. RESULTS: In the base case analysis, the average
      cost per patient (euros in 2003) of a life treatment, considering a life
      expectancy of 53 years, would be 620,205, 1,047,836, 1,006,014, 1,161,638 and
      968,157 euros with Imurel, all interferons, Avonex, Rebif and Betaferon,
      respectively. Therefore, the saving with Imurel would range between 327,000 and
      520,000 euros approximately. The quality-adjusted life years (QALY) obtained with
      Imurel or interferons would be 10.08 and 9.30, respectively, with an average gain
      of 0.78 QALY per patient treated with Imurel. The sensitivity analyses confirmed
      the robustness of the base case. The cost of one additional QALY with interferons
      would range between 413,000 and 1,308,000 euros approximately in the hypothetical
      worst scenario for Imurel. CONCLUSIONS: For a typical patient with RRMS,
      treatment with Imurel would be more efficient than interferons and would dominate
      (would be more efficacious with lower costs) beta interferon.

PMID- 15973635
TI  - [Effectiveness and safety of oxcarbazepine in chronic neuropathic pain: a study
      of 40 cases].
AB  - INTRODUCTION: Neuropathic pain (NP) often fails to respond to the commonly
      established analgesic treatment. This fact, together with the existence of side
      effects, has led to the need to evaluate the analgesic effectiveness of
      antiepileptic drugs, which, as in the case of oxcarbazepine (OXC), are a valid
      alternative. AIMS: The aim of this study was to evaluate the effectiveness and
      safety of OXC in patients suffering from chronic NP. PATIENTS AND METHODS: We
      conducted a prospective, open study involving a series of 40 patients diagnosed
      with a long history of NP, which was previously resistant to different kinds of
      treatment with anticonvulsants, non-steroidal anti-inflammatory (NSAI) drugs,
      opiates and adjuncts. Patients were treated with OXC and they were evaluated in
      both the basal (prior to treatment) and final visits (after treatment) by means
      of the visual analogue scale (VAS), SF-McGill questionnaire and the Lattinen
      test. The patient's general impression of the result was also obtained. The
      statistical analysis was performed by calculating the "effect size", by computing
      Cohen's d. RESULTS: Treatment with OXC diminishes different symptomatic
      variations of this pain, but especially so in the case of lancinating discharges
      (d = 0.87, important effect) and burning pain (d = 0.60, moderate-important
      effect), although the allodynia (d = 0.48, moderate effect) also improved with
      treatment. In the opinion of the patients themselves, response to treatment was
      good or very good in 50% of cases. The chief side effects observed were
      dizziness, drowsiness and abdominal upsets. CONCLUSIONS: OXC can be seen as a
      therapeutic alternative to be taken very much into account in patients with NP
      having different aetiologies; it has a good benefit-risk ratio and is a form of
      treatment that is well accepted by patients.

PMID- 15973636
TI  - [Prevalence of attention deficit hyperactivity disorder in Colombian children and
      teenagers].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common
      neurobehavioural disorder among schoolchildren. It may persist into adulthood and
      affect performance in the academic, social, occupational and familial spheres,
      and increase the use and abuse of alcohol and psychoactive substances and the
      risk of having an accident. Its prevalence throughout the world varies widely and
      further knowledge about this situation would be valuable for the development of
      policies in the sector of education. AIMS: The aim of this research was to
      determine the prevalence of ADHD and its distribution according to subtypes in
      schoolchildren from Sabaneta, Antioquia, Colombia, in 2001. SUBJECTS AND METHODS:
      The analysis involved a cross-sectional descriptive study using a representative
      randomised multistage sample (which was proportional to the size of the groups)
      of schoolchildren between 4 and 17 years old. Measurement was performed in two
      stages, first by application of a screening form according to DSM IV criteria,
      and later a structured interview, Conners' and Intelligence tests. RESULTS:
      Prevalence was found to be 20.4% and 15.8% if only children with an intelligence
      quotient of 80 or above were considered. The combined subtype was the most
      frequent, with 9.6%. In public schools it was 16.2%, private 15.3%, age group
      from 7-11 years 16.9%, 12-17 years old 14.2%, males 20.9%, females 10.1%, low
      14.7%, medium 17.4% and high socioeconomic level 10.7%, with a male to female
      prevalence ratio of 3.88 to 1. CONCLUSIONS: Prevalence of ADHD in the school
      population in a municipality in the Metropolitan Area of Medellin, Colombia, is
      high. The most frequent subtype was the combined type, which was predominant in
      males, had repercussions on academic performance and low proportions of
      pharmacological interventions for the disorder (15%). Programmes must be
      developed for the detection of this problem and subsequent intervention in the
      school population.

PMID- 15973637
TI  - [Cerebrovascular disease in a tertiary care hospital. The current situation and
      points to be improved].
AB  - INTRODUCTION: Caring for patients suffering from a cerebrovascular diseases
      requires a large quantity of resources which must be optimised. The aim of this
      study is to analyse the management of stroke in a tertiary care hospital.
      PATIENTS AND METHODS: All admissions with a diagnosis of stroke were analysed
      retrospectively for the year 2003. Length of stay, computed tomography in the
      Emergency Room, origin, previous admissions during the last year, presence of
      vascular risk factors, stroke subtype, complications and mortality during
      admission and destination when discharged from hospital, were all recorded.
      RESULTS: 936 patients were admitted to hospital with a diagnosis of stroke.
      80.22% corresponded to acute ischaemic strokes (27.14% lacunar, 18.57% transient
      ischaemic attacks, 10.25% cardioembolic, 15.44% aterothrombotic, 8.44% infarct of
      undetermined cause, 0.24% unusual aetiology) and 19.78% corresponded to
      haemorrhagic strokes (13.99% intraparenchymatous hemorrhage, 5.79% subarachnoid
      hemorrhage). Intra-hospital mortality was 5.3%. 11% suffered from complications
      while in hospital, and average length of stay was 10.4 days, being much longer
      for those patients discharged to a medium-long stay centre (17.5 days). Compared
      to other series, the incidence of cardioembolic and aterothrombotic subtypes of
      stroke is low. However, because of the inclusion of neurosurgical patients, an
      increase of cerebral haemorrhages is observed. CONCLUSIONS: Intra-hospital
      morbidity and mortality and average length of stay in our series are consistent
      with those from other centres of similar characteristics. A better coordination
      with medium-long stay centres along with the presence of neurologists on call,
      would certainly improve these variables.

PMID- 15973638
TI  - [Adult-onset subacute sclerosing panencephalitis: clinicopathological findings].
AB  - INTRODUCTION: Subacute sclerosing panencephalitis is a disease affecting the
      central nervous system that is produced by persistent infection by a defective
      measles virus. This disease is very infrequent and its incidence has gone down
      even further in western countries since the introduction of generalised measles
      vaccinations. Onset of the disease is usually during infancy or adolescence.
      Reports of cases beginning during adulthood are scarce. CASE REPORT: We describe
      the case of a 30-year-old female with a slowly progressive subacute clinical
      picture consisting in behavioural disorders, with defrontalisation, cortico
      subcortical cognitive impairment, long tract signs and visual disorders, which
      led the patient into a vegetative state. Four years after the onset of symptoms
      the patient died. The different electroencephalogram recordings performed did not
      show any periodic activity and magnetic resonance imaging of the head revealed
      cerebral atrophy with hyperintense lesions in T2 sequences in white matter. The
      histological study of the brain showed a chronic inflammatory infiltration with
      neuronal loss and demyelination, as well as intranuclear inclusions and
      neurofibrillary degeneration. CONCLUSIONS: The appearance of subacute sclerosing
      panencephalitis in adulthood is exceptional. Diagnosis requires a high degree of
      clinical suspicion, above all in the absence of typical symptoms, such as
      myoclonias or periodic complexes in EEG recordings.

PMID- 15973639
TI  - [Retrospective diagnosis of congenital infection by cytomegalovirus in the case
      of one infant].
AB  - INTRODUCTION: 10-15% of asymptomatic congenital infections by cytomegalovirus
      (CMV) in the neonatal period develop persistent problems with varying degrees of
      severity, fundamentally involving neurological disorders, neurosensory hypoacusis
      and hypovision, which appear from the age of 6-9 months onwards, when a diagnosis
      is no longer possible. The PCR (polymerase chain reaction) technique can detect
      DNA of CMV in blood samples on filter paper used for screening hypothyroidism and
      metabolic pathologies that were kept from the neonatal period. CASE REPORT: A
      child aged 3 years and 8 months with delayed intrauterine growth, autism, mental
      retardation, microcephalus and neurosensory hypoacusis; periventricular
      calcifications, leukoencephalopathy and bilateral malformation of the temporal
      lobe; and a diagnosis of congenital CMV confirmed by detection of DNA by PCR in
      the blood sample on filter paper saved from the neonatal period. CONCLUSIONS: The
      retrospective study of congenital infection by CMV should be considered when
      faced with severity and varying association of delayed intrauterine growth,
      microcephalus, neurosensory hypoacusis, chorioretinitis, mental retardation,
      autism or other behavioural disorders, intracranial calcifications,
      encephaloclastic alterations, leukoencephalopathy, cortical dysplasia and
      malformations of the temporal lobe and the hippocampus. Since the filter papers
      from neonatal screening are not kept for ever, perhaps the idea of doing so ought
      to be considered, given the possibilities they offer for retrospective studies.

PMID- 15973640
TI  - [Brain vasculitis associated with drugs].
AB  - INTRODUCTION: Vasculitis or angiitis is the term used to define the inflammation
      of the vessels, either blood or lymphatic, which causes may be primary related to
      immunological disorders, or secondary, with great variety of causal factors. CASE
      REPORT: We present a very uncommon case of a 36 year old man with brain
      vasculitis associated with drugs with very peculiar characteristics in the
      imaging studies and with definite diagnosis through histopathology obtained by
      biopsy, which differs from the few reports in the literature until our days.
      CONCLUSIONS: Our report is an uncommon case of cerebral vasculitis whose clinical
      features were confusing with impressing neuroimaging studies that showed possible
      lesions due to vasculitis that was confirmed through a cerebral biopsy and
      considering that the immunological tests were negative for a primary vasculitic
      process, we concluded that it was a vasculitis secondary to drug abuse which
      represents a special interest in view of the few existing reports in literature
      with definite diagnostic methods, such as cerebral biopsy or autopsy.

PMID- 15973641
TI  - [Changing the anticholinesterase in Alzheimer's disease].
AB  - AIM: To review the available information related to the switch of one
      cholinesterase inhibitor (CEI) by other CEI in Alzheimer's disease. DEVELOPMENT
      AND CONCLUSIONS: The distinct pharmacological profile of CEI supports the switch,
      which can be considered in three scenarios: poor tolerability, lack of efficacy
      at the beginning of the treatment and long-term loss of efficacy. A poor
      tolerability to one CEI predisposes to not tolerating a second CEI, but this is
      not so much when a washout period is kept. Under these circumstances, the switch
      can be performed if the adverse events are minor and do not represent a risk for
      the patient. Switching the CEI is also advisable in case of lack of efficacy at
      the beginning of treatment. In this situation, some observational studies have
      shown a response to rivastigmine in approximately half of patients who had not
      responded to donepezil. Switching in other directions is also reasonable, but has
      been less investigated. As for the third scenario, i.e. long-term loss of
      efficacy, there are not sufficient available data to indicate the switch. This
      practice should be kept for research purposes only.

PMID- 15973642
TI  - [The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: IV. General
      principles of antiepileptic polytherapy and therapeutic strategies in refractory
      epilepsy].
AB  - AIMS: The objective of this work was to produce a scientific evidence-based guide
      to clinical practice dealing with the basic questions concerning the treatment of
      epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia
      Epilepsy Society, made up of six neurologists, three neuropaediatricians, one
      neurosurgeon and a pharmacologist, all of whom were deeply involved and
      experienced in epilepsy, conducted a thorough review of the literature in search
      of all the evidence available on the proposed subject matter. The following
      databases were used: MEDLINE, Cochrane Library and the databases of several
      clinical practice guidelines (National Guideline Clearinghouse, National
      Institute of Clinical Excellence and the American Academy of Neurology's Clinical
      Guidelines). The Guide was set out in seven sections and was published in four
      parts. From a total number of 187 relevant documents, the committee found 63
      examples of scientific evidence and 91 therapeutic recommendations. These were
      tabulated and classified according to the European Federation of Neurological
      Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The
      results of this survey provide scientific evidence-based clinical guidelines that
      are useful, simple and applicable at different levels of health care.

PMID- 15973644
TI  - [Syndrome of inappropriate antidiuretic hormone secretion secondary to
      carbamazepine].

PMID- 15973646
TI  - Hydrogen-shift isomerism: mass spectrometry of isomeric benzenesulfonate and 2-,
      3- and 4-dehydrobenzenesulfonic acid anions in the gas phase.
AB  - The isomeric 3- and 4-dehydrobenzenesulfonic acid anions b and c were prepared by
      collision induced dissociation (CID) of the [M - H](-) ions of isomeric
      sulfobenzoic acids obtained by negative electrospray ionization (ESI). The CID
      spectra (MS(3)) of anions b and c are different from each other, and both are
      different from that of the isomeric benzenesulfonate anion a, obtained from
      benzenesulfonic acid. The stability of ions b and c shows that 1,2-proton
      transfer does not take place in this system under the conditions of the CID
      experiment. Density functional (DFT) calculations at B3LYP/6-31+G(2d,p) level of
      theory show that benzenesulfonate anion a is the most stable isomer, and the
      energies of isomers b and c are higher by more than 65 kcal mol(-1). The
      calculated energies of the transition states involved in the 1,2-hydrogen
      migration leading to the interconversion of the isomeric anions are very high
      (>120 kcal mol(-1)relative to ion a, barrier energies >55 kcal mol(-1)), much
      higher than those of transition structures leading to fragmentation. This
      situation does not allow isomerization of ions b and c to a, under the conditions
      of the CID experiments. The isomeric 2-dehydrobenzenesulfonic acid anion
      isomerizes to the benzenesulfonate anion a by a facile proton transfer from the
      SO(3)H group to the adjacent position 2. The results of this work indicate that
      the gas phase deprotonation of meta- and para-sulfobenzoic acids is a kinetically
      controlled process.

PMID- 15973647
TI  - Factors that influence Spanish- and English-speaking participants' decision to
      enroll in cancer randomized clinical trials.
AB  - Cancer randomized clinical trial (RCT) participation is low, particularly among
      ethnic and racial minorities. Hispanic enrollment is far below their
      representation in the US population, yet their cancer burden is higher. Little is
      known from the patient perspective about factors which influence the decision to
      enroll in RCTs. We asked Spanish- and English-speaking individuals what factors
      influence decisions about cancer RCT participation. Eight focus groups were
      conducted with 55 participants (25 Spanish and 30 English-speaking). The groups
      were taped, transcribed, and analyzed for themes. Six major themes emerged:
      patient-provider communication, personal relationship with provider, involvement
      of significant others in decision making, role of faith, need for information,
      and impact of discrimination on decision making. Both similarities (e.g. need for
      comprehensive information) and differences (e.g. need for provider
      acknowledgement of emotional and spiritual concerns) were found between Spanish-
      and English-speaking participants. Among Spanish-speaking participants, level of
      education was differentially related to decision-making themes. Implications for
      providers are discussed.

PMID- 15973648
TI  - Posterior compartment prolapse on two-dimensional and three-dimensional pelvic
      floor ultrasound: the distinction between true rectocele, perineal hypermobility
      and enterocele.
AB  - OBJECTIVES: Posterior compartment descent may encompass perineal hypermobility,
      isolated enterocele or a 'true' rectocele due to a rectovaginal septal defect.
      Our objective was to determine the prevalence of these conditions in a
      urogynecological population. METHODS: One hundred and ninety-eight women were
      clinically evaluated for prolapse and examined by translabial ultrasound, supine
      and after voiding, using three-dimensional capable equipment with a 7-4-MHz
      volume transducer. Downwards displacement of rectocele or rectal ampulla was used
      to quantify posterior compartment prolapse. A rectovaginal septal defect was seen
      as a sharp discontinuity in the ventral anorectal muscularis. RESULTS:
      Clinically, a rectocele was diagnosed in 112 (56%) cases. Rectovaginal septal
      defects were observed sonographically in 78 (39%) women. There was a highly
      significant relationship between ultrasound and clinical grading (P < 0.001). Of
      112 clinical rectoceles, 63 (56%) cases showed a fascial defect, eight (7%)
      showed perineal hypermobility without fascial defect, and in three (3%) cases
      there was an isolated enterocele. In 38 (34%) cases, no sonographic abnormality
      was detected. Neither position of the ampulla nor presence, width or depth of
      defects correlated with vaginal parity. In contrast, age showed a weak
      association with rectal descent (r = -0.212, P = 0.003), the presence of fascial
      defects (P = 0.002) and their depth (P = 0.02). CONCLUSIONS: Rectovaginal septal
      defects are readily identified on translabial ultrasound as a herniation of
      rectal wall and contents into the vagina. Approximately one-third of clinical
      rectoceles do not show a sonographic defect, and the presence of a defect is
      associated with age, not parity.

PMID- 15973649
TI  - Development of a liquid chromatography/tandem mass spectrometry method for the
      quantification of fumonisin B1, B2 and B3 in cornflakes.
AB  - A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the
      determination of fumonisin B1 (FB1), B2 (FB2) and B3 (FB3) in cornflakes is
      described. During method development, special attention was paid to the selection
      of a suitable internal standard (IS) in order to offer a good alternative for
      deuterated FB1. In this respect, the C12-sphinganine analogue (2S,3R)-2
      aminododecane-1,3-diol was chosen because of its structural similarity to the
      fumonisin backbone and its chromatographic elution between the target analytes.
      For the extraction of the fumonisins from the cornflakes matrix, MeOH/H2O
      (adjusted to pH 4 with 0.1 M HCl; 70:30, v/v), ACN/MeOH/H(2)O (25:25:50, v/v/v)
      and acidified ACN/MeOH/H2O (25:25:50, v/v/v; pH 4) were evaluated. Preference was
      given to acidified MeOH/H2O (70:30, v/v) with mean recoveries (n=12) for FB1, FB2
      and FB3 of, respectively, 84+/-10, 78+/-7 and 85+/-9%. Cleanup was performed
      using immunoaffinity columns (FumoniTest, VICAM). The chromatography was
      performed under isocratic conditions at a flow of 0.3 mL min-1 with a mobile
      phase consisting of ACN/H2O (60:40, v/v) containing 0.3% formic acid. The mass
      spectrometer was operated in the positive electrospray ionization (ESI+) mode
      using multiple reaction monitoring (MRM). An intralaboratory validation was
      conducted with fortified samples determining limits of detection (LOD), limits of
      quantification (LOQ), precision, trueness, specificity and measurement
      uncertainty. The LOD concentrations for FB1, FB2 and FB3 were 20, 7.5 and 12.5
      microg/kg. The LOQs were 40 microg/kg for FB1, 15 microg/kg for FB2 and 25
      microg/kg for FB3. The coefficients of variation (CVs) under repeatability
      conditions varied from 11 to 13% for FB1, from 9 to 14% for FB2 and from 7 to 10%
      for FB3. Under within-laboratory reproducibility conditions, the CVs ranged from
      12 to 17% for FB1, from 9 to 16% for FB2 and from 7 to 13% for FB3. The percent
      bias for FB1 varied from -12 to -10%, while for FB2 and FB3 bias ranged,
      respectively, from -4 to -2% and from -12 to -5%. The expanded measurement
      uncertainties for FB1, FB2 and FB3 were, respectively, 19, 18 and 22%.

PMID- 15973653
TI  - Hyperexcitable polymodal and insensitive nociceptors in painful human neuropathy.
AB  - Six patients with chronic pain, mechanical and thermal hyperalgesia/allodynia,
      and cutaneous vasodilatation starting distally in their extremities, were
      evaluated using clinical and neurophysiological methods and microneurography.
      Evidence of small-fiber polyneuropathy was documented in all, but the etiology
      remained cryptogenic in several. Different forms of hyperexcitability were
      detected by microneurography in both common polymodal and mechanically
      insensitive C nociceptors, which explain all the somatosensory abnormalities.
      Signs of hyperexcitability included reduced receptor threshold (accounting for
      mechanical and heat allodynias), spontaneous C nociceptor discharge (explaining
      spontaneous "burning" pain and antidromic vasodilatation), and multiplied
      nociceptor responses to stimulation (accounting for hyperalgesia). The clinical
      and electrophysiological profiles of these patients resemble the experimental
      syndrome evoked by application of capsaicin to the skin. This similarity, and the
      striking heat dependence of the spontaneous pain, suggest that a common feature
      may be altered expression or modulation of vanilloid 1 receptor, provoking
      abnormal nociceptor discharges.

PMID- 15973654
TI  - Utility of coronary physiologic hemodynamics for bifurcation, aorto-ostial, and
      ostial branch stenoses to guide treatment decisions.

PMID- 15973655
TI  - Early administration of abciximab in patients with acute myocardial infarction
      improves angiographic and clinical outcome after primary angioplasty.
AB  - Adjunctive use of abciximab during percutaneous coronary intervention (PCI) for
      acute myocardial infarction (AMI) improves clinical outcome. This study addresses
      the outcome of patients with AMI treated with abciximab, initiated either before
      transport to a PCI center (early group) or immediately upon arrival at the
      catheterization laboratory (late group) for primary PCI. Of 446 consecutive
      patients with AMI, angiographic data and clinical complications were evaluated up
      to 6 months after primary PCI. Patients received abciximab before transport
      (early group; n = 138) or just before the intervention (late group; n = 308).
      Baseline data, including transport time (45 +/- 15 min; range, 15-60 min), were
      comparable in both groups. Early reperfusion was more prevalent in the early
      group (35% vs. late 19%; P < 0.001). Furthermore, a better final TIMI 3 flow was
      noted in the early group (91% vs. late 83%; P = 0.05). Although mortality
      reduction attributable to early abciximab treatment could not be demonstrated,
      major adverse cardiac events (MACE) occurred in 27% in the early group and 36% in
      the late group (P = 0.05). Revascularization rates were similar, but repeat acute
      coronary syndromes were less frequent in the early group (11% vs. late group 20%;
      P = 0.04). In multivariate analysis, cardiogenic shock, out-of-hospital cardiac
      arrest, and previously known coronary artery disease were independent predictors
      of higher MACE rate, whereas early reperfusion and final TIMI 3 flow reduced 6
      month MACE rate. Abciximab pretreatment of patients with AMI for primary PCI
      results in better initial and final TIMI flow and tends to improve 6-month
      clinical outcome.

PMID- 15973656
TI  - Selective versus exclusive use of sirolimus-eluting stent implantation in
      multivessel coronary artery disease.
AB  - Sirolimus-eluting stents (SESs; Cypher) have demonstrated a significant reduction
      in restenosis rates when compared to bare metal stents (BMSs). The purpose of
      this study was to evaluate the strategy of exclusive use of two SESs versus the
      combination of one BMS and one SES for two-vessel coronary artery disease (CAD).
      It was found that the selective use of one SES combined with one BMS in patients
      undergoing percutaneous coronary intervention that requires more than one stent
      is safe, feasible, and associated with favorable procedural, 30-day, and 6-month
      clinical outcomes when compared to the exclusive use of SESs.

PMID- 15973657
TI  - Comparison of high-resolution echo-planar spectroscopic imaging with conventional
      MR imaging of prostate tumors in mice.
AB  - High spectral and spatial resolution (HiSS) MRI of rodent tumors has previously
      been performed using conventional spectroscopic imaging to obtain images with
      improved contrast and anatomic detail. The work described here evaluates the use
      of much faster echo-planar spectroscopic imaging (EPSI) to acquire HiSS data from
      rodent tumor models of prostate cancer. A high-resolution EPSI pulse sequence was
      implemented on a 4.7 T Bruker scanner. Three-dimensional EPSI data were Fourier
      transformed along the k-space and temporal (free-induction decay) axes to produce
      detailed water and fat spectra associated with each small image voxel. The data
      were used to generate images of spectral parameters, e.g. peak-height images for
      each small voxel. Two variants of EPSI were performed; gradient-echo or spin-echo
      excitation with EPSI readout. These imaging methods were tested in commonly used
      rodent prostate cancers, including seven mice implanted with non-metastatic AT2.1
      (n=3) and metastatic AT3.1 (n=4) prostate tumors on the hind leg, and 10 mice
      implanted with LNCaP prostate cancers in situ. The peak-height images derived
      from EPSI datasets provide more detailed tumor anatomy, improved signal-to-noise
      and contrast-to-noise ratios compared with the gradient-echo or spin-echo images
      at all echo times. The results suggest that HiSS MRI data from small animal
      models of prostate cancer can be acquired using EPSI, and that this approach
      improves imaging of heterogeneous tissue and vascular environments inside the
      tumors compared with conventional MR techniques.

PMID- 15973658
TI  - Firing rates of motor units during strong dynamic contractions.
AB  - Muscle behavior is usually studied during isometric contractions but many tasks
      include contractions that involve changes in muscle length. Our aim was to record
      motor unit action potentials and surface electromyograms (EMGs) from triceps
      brachii muscles during rhythmic dynamic contractions (3-s concentric, 3-s
      eccentric; 40 degrees/s; four subjects) performed at the highest voluntary forces
      subjects could exert (maximal concentric contraction) and at various submaximal
      intensities. Mean unit firing rates and surface EMG increased significantly with
      contraction intensity in both concentric and eccentric contractions, but at each
      intensity mean concentric values were significantly higher than eccentric values.
      In contrast, mean unit firing rates and surface EMGs were similar during maximal
      concentric and maximal isometric contractions. These data suggest muscles were
      activated maximally during the strongest concentric contractions but submaximally
      during the strongest eccentric efforts. After estimated eccentric contraction
      intensity was adjusted using surface EMG data, mean unit firing rates during
      eccentric contractions were still lower than the concentric values. Thus,
      protective mechanisms may limit motor unit firing rates during forceful
      lengthening contractions to minimize damage.

PMID- 15973659
TI  - Tracking motor unit action potentials in the tibialis anterior during fatigue.
AB  - New surface electromyogram (SEMG) techniques offer the potential to advance
      knowledge of healthy and diseased motor units. Conduction velocity (CV)
      estimates, obtained from indwelling electrodes, may provide diagnostic
      information, but the standard method of CV estimation from SEMG may be of only
      limited value. We developed a motor unit (MU) tracking algorithm to extract motor
      unit conduction velocity (MUCV) and motor unit action potential (MUAP) amplitude
      estimates from SEMG. The technique is designed to provide a noninvasive means of
      accessing fatigue and recruitment behavior of individual MUs. We have applied
      this MU tracking algorithm to SEMG data recorded during isometric fatiguing
      contractions of the tibialis anterior (TA) muscle in nine healthy subjects, at
      30%-40% maximum voluntary contraction (MVC). The results reveal that MUCVs and
      MUAP amplitudes of individual MUs can be estimated and tracked across time. Time
      related changes in the MU population may also be monitored. Thus, the SEMG
      technique employed provides insight into the behavior of the underlying muscle at
      the MU level by noninvasive means.

PMID- 15973660
TI  - Neurologic complications after surgery for obesity.
AB  - Bariatric surgical procedures are increasingly common. In this review, we
      characterize the neurologic complications of such procedures, including their
      mechanisms, frequency, and prognosis. Literature review yielded 50 case reports
      of 96 patients with neurologic symptoms after bariatric procedures. The most
      common presentations were peripheral neuropathy in 60 (62%) and encephalopathy in
      30 (31%). Among the 60 patients with peripheral neuropathy, 40 (67%) had a
      polyneuropathy and 18 (30%) had mononeuropathies, which included 17 (94%) with
      meralgia paresthetica and 1 with foot drop. Neurologic emergencies including
      Wernicke's encephalopathy, rhabdomyolysis, and Guillain-Barre syndrome were also
      reported. In 18 surgical series reported between 1976 and 2004, 133 of 9996
      patients (1.3%) were recognized to have neurologic complications (range: 0.08
      16%). The only prospective study reported a neurologic complication rate of 4.6%,
      and a controlled retrospective study identified 16% of patients with peripheral
      neuropathy. There is evidence to suggest a role for inflammation or an
      immunologic mechanism in neuropathy after gastric bypass. Micronutrient
      deficiencies following gastric bypass were evaluated in 957 patients in 8
      reports. A total of 236 (25%) had vitamin B(12) deficiency and 11 (1%) had
      thiamine deficiency. Routine monitoring of micronutrient levels and prompt
      recognition of neurological complications can reduce morbidity associated with
      these procedures.

PMID- 15973661
TI  - Evolution of hand dysfunction and symptoms in untreated carpal tunnel syndrome.
AB  - The Italian Carpal Tunnel Syndrome (CTS) Study Group assessed the evolution of
      symptoms and hand dysfunction through validated, patient-oriented measures in 264
      patients with 354 hands affected by untreated idiopathic CTS (follow-up 10-15
      months). The evolution of symptoms and hand dysfunction was positively related.
      Only in 3% was there discordance between hand dysfunction and symptom evolution.
      Thus, in patients with CTS, hand dysfunction and symptoms evolve in parallel.

PMID- 15973662
TI  - Repeat needle biopsies combined with clinical observation are safe and accurate
      in the management of a solitary pulmonary nodule.

PMID- 15973664
TI  - Outcome of patients with acute myelogenous leukemia after second salvage therapy.
AB  - BACKGROUND: Although the prognosis is poor for patients with acute myelogenous
      leukemia (AML) who have disease recurrence after frontline therapy, this is a
      general reflection of first salvage therapies. The outcome of patients undergoing
      second salvage therapy in relation to complete response (CR) rates and survival
      has not been documented. The authors analyzed the outcome of patients with AML
      undergoing second salvage therapy, and identified prognostic factors associated
      with response and survival. METHODS: The records of 594 patients with AML
      undergoing second salvage therapy from 1980 until 2004 were reviewed. The patient
      median age was 50 years. Salvage therapy included allogeneic stem cell
      transplantation (SCT) in 74 patients, standard-dose cytosine arabinoside (ara-C)
      combinations in 30 patients, high-dose ara-C combinations in 171 patients, non
      ara-C combinations in 73 patients, and Phase I-II single agents in 246 patients.
      RESULTS: Overall, 76 patients (13%) achieved CR. The median CR duration was 7
      months. The median survival was 1.5 months, and the 1-year survival rate was 8%.
      A multivariate analysis of prognostic factors for CR identified the following 6
      independent adverse factors: first CR duration < 6 months; second CR duration < 6
      months; salvage therapy not including allogeneic SCT; non-inversion 16 AML;
      platelet counts < 50 x 10(9)/L, and leukocytosis > 50 x 10(9)/L. Patients were
      divided into low-risk (1-2 adverse factors; 8%), intermediate 1 (3 factors; 20%),
      intermediate 2 (4 factors; 38%), and high-risk groups (5-6 factors; 33%) with
      respective CR rates of 54%, 26%, 8%, and 0%. The respective 1-year survival rates
      were 36%, 21%, 6%, and 1%. A multivariate analysis for survival identified the
      following 7 independent adverse factors: first CR duration < 12 months; second CR
      duration < 6 months; bilirubin level > or = 1 mg/dL; albumin level < 3 g/dL; age
      > 60 years; bone marrow blasts > or = 50%; and year of therapy before 1991.
      Patients were divided into low-risk (0-2 adverse factors; 39%), intermediate (3
      factors; 27%), and high-risk groups (> or = 4 factors; 34%) with estimated 1-year
      survival rates of 22%, 6%, and 0%, respectively. The respective CR rates were
      26%, 8%, and 2%. CONCLUSIONS: The current analysis established the outcome and
      prognostic factors associated with second salvage therapy in AML. It also
      proposed risk models and groups that could be used for comparison of results of
      present and future investigational strategies.

PMID- 15973665
TI  - Analysis of clonal immunoglobulin heavy chain rearrangements in ocular lymphoma.
AB  - BACKGROUND: The morphologic diagnosis of primary and metastatic intraocular
      lymphoma (IOL) was made difficult by the paucicellular specimens with fragile
      populations of lymphocytes retrieved through pars plana vitrectomy (PPV). The
      analysis of immunoglobulin heavy chain (IgH) gene rearrangements (AIGHR) was used
      as an adjunct to cytopathology and flow cytometry in systemic lymphoma. In IOL,
      the sensitivity and specificity of AIGHR are unknown. METHODS: The authors
      reviewed the clinical records of patients who underwent PPV for suspicion of IOL
      at the Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary
      (Boston, MA) between 2000 and 2002. AIGHR was performed as a routine diagnostic
      test on cell lysates isolated from < 0.5 mL of vitreous fluid. The authors used
      seminested polymerase chain reaction (PCR) with consensus primers for the VDJ
      region of the IgH gene. PCR products were analyzed by polyacrylamide gel
      electrophoresis. RESULTS: Thirty patients (37 specimens) with chronic vitritis
      and 17 patients (23 specimens) with IOL were included. The specificity of
      vitreous fluid cytopathology, flow cytometry, and AIGHR was 1.0, and the
      sensitivity values were 0.24, 0.36, and 0.64, respectively. AIGHR was negative in
      two patients for whom cytopathology or flow cytometry revealed the diagnosis of
      lymphoma. Clonal IGHR was found in four specimens classified as negative for
      lymphoma based on cytopathology and flow cytometry. CONCLUSIONS: AIGHR
      supplemented cytopathology and flow cytometry to increase the diagnostic yield in
      IOL.

PMID- 15973666
TI  - Pro-gastrin-releasing peptide as a factor predicting the incidence of brain
      metastasis in patients with small cell lung carcinoma with limited disease
      receiving prophylactic cranial irradiation.
AB  - BACKGROUND: Prophylactic cranial irradiation (PCI) reduces the incidence of brain
      metastasis with an effect on overall survival in patients with small cell lung
      carcinoma (SCLC). In spite of multidisciplinary intensive treatment approaches,
      many patients still experience brain metastasis. The authors retrospectively
      analyzed the characteristics of the first failure event due to brain metastasis
      (FBM) in patients treated with PCI. METHODS: Between January 1990 and April 2004,
      71 patients with limited disease SCLC were treated with PCI after completing
      systemic treatment at the National Cancer Center Hospital (Tokyo, Japan).
      Univariate and multivariate analyses were used to identify factors related to FBM
      and survival. RESULTS: The FBM and overall incidence of brain metastasis (OBM)
      were 16.9 % (12 of 71) and 26.8% (19 of 71), respectively. Median time to
      progressive disease and median survival were 8.4 months and 21.6 months,
      respectively. Elevation of pro-gastrin-releasing peptide (Pro GRP) level before
      PCI was found to be a significant predictive and prognostic factor for FBM, OBM,
      and survival on multivariate analysis (P = 0.007, P = 0.025, and P = 0.009,
      respectively). CONCLUSIONS: An elevated Pro GRP level before PCI was found to be
      significantly related to FBM and survival, and should be considered before PCI is
      performed.

PMID- 15973667
TI  - Phase II study of oxaliplatin in patients with recurrent or refractory non
      Hodgkin lymphoma.
AB  - BACKGROUND: Oxaliplatin is a platinum derivative with a broad range of anticancer
      activity. The objective of the current Phase II trial was to investigate the
      activity of oxaliplatin in patients with recurrent or refractory non-Hodgkin
      lymphoma (NHL). METHODS: Patients with recurrent and refractory NHL who received
      a maximum of 3 previous chemotherapy regimens were considered eligible if they
      had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate
      organ function. Oxaliplatin was administered in an outpatient setting at a dose
      of 130 mg/m(2) by 2-hour intravenous infusion every 21 days for < or = 6 cycles
      in the absence of disease progression. RESULTS: Thirty-one patients (23 with
      aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable
      for toxicity, response, and survival. The median patient age was 62 years, and
      20% of the patients previously received platinum-containing therapy. Eighty-three
      percent of the patients were refractory to their last treatment regimens. Grade 3
      and 4 toxic effects (according to the National Cancer Institute's Common Toxicity
      Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and
      thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence
      interval, 13-47%) of the patients. Responses were observed in platinum-naive
      patients as well as in those previously treated with platinum. The overall median
      failure-free survival duration was 3.0 months (range, 0.1-18.1 months).
      CONCLUSIONS: Oxaliplatin had favorable single-agent activity in previously
      treated patients with refractory lymphoma. The favorable safety profile and the
      ease of its administration in outpatient settings warrant investigating it in
      combination with other active drugs for the treatment of recurrent and refractory
      NHL.

PMID- 15973668
TI  - Cognitive impairment, fatigue, and cytokine levels in patients with acute
      myelogenous leukemia or myelodysplastic syndrome.
AB  - BACKGROUND: The objective of the current study was to assess the correlations
      between cognitive function, fatigue, quality of life, and circulating cytokine
      levels in patients with acute myelogenous leukemia (AML) and myelodysplastic
      syndrome (MDS). METHODS: Fifty-four patients with AML/MDS were seen for
      pretreatment evaluation of their cognitive function and symptoms. Fifty percent
      of the sample was reevaluated 1 month later, when response to protocol
      chemotherapy was assessed. RESULTS: A significant proportion of patients had
      impaired cognitive function prior to the institution of chemotherapy. Sixty-five
      percent of patients also experienced significant fatigue. Levels of the
      circulating cytokines interleukin 1 (IL-1), IL-1 receptor antagonist (IL-1RA), IL
      6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were elevated highly
      compared with normal controls. Higher IL-6 levels were associated with poorer
      executive function, whereas higher IL-8 levels were associated with better memory
      performance. IL-6, IL-1RA, and TNF-alpha levels were related to ratings of
      fatigue. Fatigue and cognitive dysfunction were unrelated. Hemoglobin levels were
      not associated significantly with either cognitive dysfunction or fatigue.
      Patients who obtained a complete response tended to have better fine motor
      control at baseline and lower circulating IL-1 levels. Treatment did not have a
      significant impact on cognition, although fatigue levels tended to increase.
      CONCLUSIONS: Patients with AML/MDS are highly symptomatic and experience
      cognitive impairment and fatigue before the initiation of their treatment. The
      current results indicated a correlation between these symptoms and levels of
      circulating cytokines, providing some support to the hypothesis that cancer
      related symptoms are related at least in part to cytokine-immunologic activation.
      Elucidation of immunologic correlates of symptoms will allow for targeted
      interventions.

PMID- 15973669
TI  - Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3
      antagonist and a corticosteroid in patients receiving anthracyclines or
      cyclophosphamide in addition to high-dose cisplatin: analysis of combined data
      from two Phase III randomized clinical trials.
AB  - BACKGROUND: The tendency of chemotherapeutic regimens to cause vomiting is
      dependent on the individual drugs in the regimen. The authors analyzed data
      combined from 2 Phase III trials to assess the effect of the neurokinin-1 (NK(1))
      antagonist aprepitant combined with a 5HT(3) antagonist plus a corticosteroid in
      a subpopulation receiving > 1 emetogenic chemotherapeutic agent. METHODS: In the
      current study, 1043 cisplatin-naive patients (42% were women) receiving cisplatin
      based (> or = 70 mg/m(2)) chemotherapy were assigned randomly to a control
      regimen (ondansetron [O] 32 mg intravenously and dexamethasone [D] 20 mg orally
      on Day 1; D 8 mg twice daily on Days 2-4) or an aprepitant (A) regimen (A 125 mg
      orally plus O 32 mg and D 12 mg on Day 1; A 80 mg and D 8 mg once daily on Days 2
      3; and D 8 mg on Day 4). Randomization was stratified for use of concomitant
      chemotherapy and female gender. The primary end point was complete response (no
      vomiting and no rescue therapy) on Days 1-5 (0-120 hours). Data were analyzed by
      a modified intent-to-treat approach, and logistic regression was used to make
      treatment comparisons among patients receiving the most frequently coadministered
      emetogenic concomitant chemotherapy (Hesketh level > or = 3). RESULTS: Among the
      approximately 13% of patients (n = 81 for A; n = 80 for control) who received
      additional emetogenic chemotherapy (doxorubicin or cyclophosphamide), the
      aprepitant regimen provided a 33 percentage-point improvement in the complete
      response rate compared with the control regimen. Among the general population,
      the advantage with aprepitant was 20 percentage points. CONCLUSIONS: The current
      analysis of > 1000 patients from 2 large randomized trials showed that in the
      subpopulation at increased risk of chemotherapy-induced nausea and vomiting due
      to concomitant emetogenic chemotherapy, the addition of aprepitant to standard
      antiemetics improved protection to an even greater extent than in the general
      study population.

PMID- 15973670
TI  - A population-based study of lung carcinoma in Pennsylvania: comparison of
      Veterans Administration and civilian populations.
AB  - BACKGROUND: Lung carcinoma remains the major cause of cancer death in North
      America and is even more common among military veterans. The objective of this
      study was to determine whether there were differences in the characteristics and
      survival of Pennsylvania patients with lung carcinoma in the Veterans
      Administration (VA) hospital system compared with patients in the rest of the
      state. METHODS: The Pennsylvania Cancer Registry was used to identify all
      patients who were diagnosed with lung carcinoma in the State of Pennsylvania from
      1995 to 1999. Patients who were treated within the Veterans Administration Health
      Care Network were identified by hospital code. Survival from the date of
      diagnosis of lung carcinoma was determined by using the Pennsylvania state
      mortality files from 1995 to 2001. RESULTS: From 1995 to 1999, 48,994 patients
      were newly diagnosed with lung carcinoma in Pennsylvania (41.2% women), including
      856 patients in the VA system (6 women). The current analysis was restricted to
      male patients (n = 28,798 men). There was no major difference in age of VA
      patients compared with non-VA patients, and the proportions of patients who had
      localized or regional stage disease were similar (49% of VA patients vs. 48% of
      non-VA patients). The proportion of black patients was much higher in the VA
      population (23%) compared with the non-VA population (9%). The median survival
      was 6.3 months for VA patients compared with 7.9 months for patients in the rest
      of the state, and the 5-year overall survival rate was 12% for VA patients
      compared with 15% for patients in the rest of the state. When survival was
      analyzed according to race, there was a significant difference in the age
      adjusted survival of white patients in the VA system compared with patients in
      the rest of the state (P = 0.0007), but no significant difference was observed
      among black patients (P = 0.92). CONCLUSIONS: The overall survival of VA patients
      with lung carcinoma in Pennsylvania was inferior to that of patients in the
      remainder of the state and this was due primarily to differences in survival
      among the white patients. Further investigation will be necessary to determine
      whether this disparity was caused by differences in socioeconomic status or
      comorbidities or whether there are systematic differences in the diagnosis,
      staging, or treatment of lung carcinoma between VA patients and civilian
      patients.

PMID- 15973671
TI  - Clopidogrel (Plavix) desensitization: a case series.
AB  - Clopidogrel (Plavix) is a thiopyridine that inhibits the ADP-dependent pathway
      for platelet activation and has been shown in numerous trials to be effective for
      a wide variety of patients with cardiovascular disease, particularly those who
      have undergone coronary stent implantation and who present with acute coronary
      syndromes. Allergic rashes are one of the common side effects of clopidogrel,
      which leads to its discontinuation. Type I (Gell and Combs classification)
      allergic reactions to drugs may be amenable to drug desensitization, allowing
      safe and prolonged use of the drug. This case series describes a protocol for
      clopidogrel desensitization over an 8-hr period using 15 doubling doses of
      clopidogrel given by mouth to achieve a maintenance dose of 75 mg a day. This
      case series suggests that patients who have had type I drug allergy to
      clopidogrel may be rapidly desensitized using this protocol. Further studies
      enrolling a larger number of patients are indicated to confirm the safety and
      efficacy of this regimen.

PMID- 15973672
TI  - A case report of type I acute aortic intramural hematoma with localized
      dissection as a complication of renal artery stenting.
AB  - Percutaneous renal artery stenting has been demonstrated as an effective
      procedure to improve blood pressure control and preserve renal function of
      patients with artherosclerotic renal artery stenosis. Although it is a relatively
      safe procedure, some serious complications, including retroperitoneal hemorrhage,
      atheroembolism, and arterial dissection, can occur. However, development of
      aortic intramural hematoma (AIH), a different clinical disease entity from the
      aortic dissection, has not been reported as a complication of the procedure. We
      report a unique case with AIH that was successfully treated with medication. A 71
      year-old woman with uncontrolled hypertension underwent percutaneous renal artery
      stenting for treatment of the ostial stenosis of the right renal artery.
      Immediately after implantation of the stent, she complained of severe back pain
      and her systolic blood pressure dropped from 170 to 80 mm Hg. Aortography showed
      about 5 cm-sized localized dissection arising from the ostium of the right renal
      artery; however, computerized tomography (CT) scans taken immediately after the
      procedure revealed DeBakey type I AIH with a localized dissection from the right
      renal artery and pericardial effusion. Because of her refusal to take surgical
      intervention, which is a standard treatment, she was stabilized with intensive
      medical treatment. After 14 days of stabilization, AIH and pericardial effusion
      resolved on the follow-up CT scans. Her blood pressure was well controlled with
      oral antihypertensive medications and she was discharged without other
      complication.

PMID- 15973673
TI  - Late thrombosis following treatment of in-stent restenosis with drug-eluting
      stents after discontinuation of antiplatelet therapy.
AB  - Drug-eluting stent usage has become commonplace for the percutaneous treatment of
      de novo coronary lesions, but the safety and efficacy profile for their evolving
      usage in restenotic lesions is largely unknown. We report three cases of
      angiographically confirmed drug-eluting stent thrombosis following treatment of
      restenotic lesions that occurred late (193, 237, and 535 days) and shortly after
      interruption of antiplatelet therapy. All three patients suffered ST elevation
      myocardial infarction, and there was one death. Further studies are necessary to
      better define the associated risk and ideal duration of antiplatelet therapy
      necessary in this cohort of patients with restenotic lesions.

PMID- 15973674
TI  - Transcatheter closure of patent ductus arteriosus with Nit-Occlud coils.
AB  - The detachable coils have been successfully used for transcatheter occlusion of
      small- to moderate-sized patent ductus arteriosus (PDA). We report our experience
      regarding the use of the Nit-Occlud coils (NOCs) for transcatheter PDA and major
      aortopulmonary collateral (MAPCA) occlusion. Single NOCs were used to close PDA
      in 26 patients, and one small and two large MAPCAs in two patients. Mean age and
      weight of the patients were 7.7 +/- 5.4 years and 20.6 +/- 11.6 kg. Mean minimum
      duct diameter was 2.8 +/- 0.8 mm; ampulla, 8.7 +/- 2.4 mm; and PDA length, 9.3 +/
      4.4 mm. Mean pulmonary artery pressure ranged from 9 to 51 mm Hg and
      pulmonary/systemic flow ratio from 1.1 to 5.8. Ductal shape was conical in 24
      patients. Route of approach was venous in 23 and arterial in 3. Successful coil
      implantation was achieved in 24/26 (92.3%). Mean procedure and fluoroscopy time
      were 67.2 +/- 22.1 and 14.9 +/- 6.5 min. The three MAPCAs were also successfully
      occluded using NOC Medium and Flex. Postimplantation angiograms revealed no leak
      in 3, a trace or small leak in 17, and a medium leak in 4 patients. Mean follow
      up was 7 +/- 5 months. Complete occlusion was achieved in 17/24 (71%) at 24 hr,
      19/24 (79%) by 1 month, 13/15 (87%) by 3 months, 14/15 (93%) by 6 months, and
      10/11 (90%) by 12 months postprocedure. Hemolysis, late embolization, duct
      recanalization, and flow disturbances were not observed. Transcatheter occlusion
      of moderate-sized PDAs and MAPCAs using NOCs seems to offer a safe, simple, and
      controlled method in pediatric patients.

PMID- 15973675
TI  - Percutaneous closure of ascending aortic pseudoaneurysm using Amplatzer septal
      occluder device: the first clinical case report and literature review.
AB  - We report the first case of the use of an Amplatzer septal occluder device to
      close a large ascending aortic pseudoaneurysm. The patient had a complex cardiac
      history with redo coronary artery bypass graft surgery, severe left ventricular
      dysfunction, and end-stage renal disease requiring hemodialysis. The procedure
      was successfully performed under fluoroscopic and 2D/3D transthoracic
      echocardiographic guidance. Six-week follow-up with both transthoracic
      echocardiography and MRI showed the device was in proper position with complete
      closure of the pseudoaneurysm.

PMID- 15973677
TI  - Structure and function relationship in the abdominal stretch receptor organs of
      the crayfish.
AB  - The structure/function relationship in the rapidly and slowly adapting stretch
      receptor organs of the crayfish (Astacus leptodactylus) was investigated using
      confocal microscopy and neuronal modeling methods. Both receptor muscles were
      single muscle fibers with structural properties closely related to the function
      of the receptors. Dendrites of the rapidly adapting neuron terminated in a common
      pile of nerve endings going in all directions. Dendrites of the slowly adapting
      neuron terminated in a characteristic T shape in multiple regions of the receptor
      muscle. The slowly adapting main dendrite, which was on average 2.1 times longer
      and 21% thinner than the rapidly adapting main dendrite, induced larger voltage
      attenuation. The somal surface area of the slowly adapting neuron was on average
      51% larger than that of the rapidly adapting neuron. Variation in the neuronal
      geometry was greatest among the slowly adapting neurons. A computational model of
      a neuron pair demonstrated that the rapidly and the slowly adapting neurons
      attenuated the dendritic receptor potential like low-pass filters with cut-off
      frequencies at 100 and 20 Hz, respectively. Recurrent dendrites were observed
      mostly in the slowly adapting neurons. Voltage signals were calculated to be
      propagated 23% faster in the rapidly adapting axon, which is 51% thicker than the
      slowly adapting axon. The present findings support the idea that the morphology
      of the rapidly and the slowly adapting neurons evolved to optimally sense the
      dynamic and the static features of the mechanical stimulus, respectively.

PMID- 15973678
TI  - Isolation, cloning, and expression of three prepro-GnRH mRNAs in Atlantic croaker
      brain and pituitary.
AB  - Three prepro-gonadotropin-releasing hormones, seabream GnRH (sbGnRH), chicken
      GnRH-II (cGnRH-II), and salmon GnRH (sGnRH) were isolated by cDNA cloning from
      the brain of the Atlantic croaker, Micropogonias undulatus. The amino acid
      sequences of croaker GnRH precursors show greatest similarities to those of the
      gilthead and red sea breams and European sea bass. In situ hybridization of
      croaker brain sections revealed more abundant sbGnRH mRNA expression in the
      preoptic area (POA) than in other brain regions. sbGnRH mRNA expression was also
      observed in the olfactory bulb (OB; but not in the terminal nerve ganglion cells
      [TNgc]), ventral telencephalon (vTEL), and anterior hypothalamus. In addition,
      specific sbGnRH mRNA signals were detected in the pituitary. cGnRH-II mRNA
      expression was limited to the midbrain tegmentum. Neuronal elements expressing
      sGnRH mRNA were detected in the OB including the TNgc, vTEL, and POA, indicating
      an overlap of the sbGnRH and sGnRH systems in certain ventral forebrain areas.
      The results of quantitative reverse transcriptase-polymerase chain reaction of
      the three GnRH mRNAs in different brain areas and the pituitary are consistent
      with their localization by in situ hybridization. Interestingly, a few sbGnRH
      mRNA-expressing neuronal elements were observed arranged in a row in the
      anteroventral hypothalamus projecting toward the pituitary. The results provide a
      morphological basis for a putative role of sbGnRH as the gonadotropin-releasing
      hormone. Moreover, localization of sbGnRH mRNA in a teleost pituitary points to
      sbGnRH synthesis, and its potential role as a local regulator, within the
      pituitary, similar to the role of GnRH-I in mammals.

PMID- 15973679
TI  - Mass spectrometric map of neuropeptide expression in Ascaris suum.
AB  - A mass spectrometric method was used for the localization and sequence
      characterization of peptides in the nervous system of the parasitic nematode
      Ascaris suum. Mass spectrometric techniques utilizing MALDI-TOF, MALDI-TOF/TOF,
      and MALDI-FT instruments were combined with in situ chemical derivatization to
      examine the expression of known and putative neuropeptides in the A. suum nervous
      system. This first attempt at peptidomic characterization in A. suum mapped the
      expression of 39 neuropeptides, 17 of which are considered to be novel and whose
      expression has not been previously reported. These analyses also revealed that
      the peptide expression profile is unique to each nervous structure and that the
      majority of peptides observed belong to the RFamide family of neuropeptides. In
      addition, four new peptide sequences with a shared C-terminal PNFLRFamide motif
      are proposed based on in situ sequencing with mass spectrometry.

PMID- 15973680
TI  - Hippocampal granule cell activity and c-Fos expression during spontaneous
      seizures in awake, chronically epileptic, pilocarpine-treated rats: implications
      for hippocampal epileptogenesis.
AB  - The process of postinjury hippocampal epileptogenesis may involve gradually
      developing dentate granule cell hyperexcitability caused by neuron loss and
      synaptic reorganization. We tested this hypothesis by repeatedly assessing
      granule cell excitability after pilocarpine-induced status epilepticus (SE) and
      monitoring granule cell behavior during 235 spontaneous seizures in awake,
      chronically implanted rats. During the first week post-SE, granule cells
      exhibited diminished paired-pulse suppression and decreased seizure discharge
      thresholds in response to afferent stimulation. Spontaneous seizures often began
      during the first week after SE, recruited granule cell discharges that followed
      behavioral seizure onsets, and evoked c-Fos expression in all hippocampal
      neurons. Paired-pulse suppression and epileptiform discharge thresholds increased
      gradually after SE, eventually becoming abnormally elevated. In the chronic
      epileptic state, interictal granule cell hyperinhibition extended to the ictal
      state; granule cells did not discharge synchronously before any of 191 chronic
      seizures. Instead, granule cells generated only low-frequency voltage
      fluctuations (presumed "field excitatory postsynaptic potentials") during 89% of
      chronic seizures. Granule cell epileptiform discharges were recruited during 11%
      of spontaneous seizures, but these occurred only at the end of each behavioral
      seizure. Hippocampal c-Fos after chronic seizures was expressed primarily by
      inhibitory interneurons. Thus, granule cells became progressively less excitable,
      rather than hyperexcitable, as mossy fiber sprouting progressed and did not
      initiate the spontaneous behavioral seizures. These findings raise doubts about
      dentate granule cells as a source of spontaneous seizures in rats subjected to
      prolonged SE and suggest that dentate gyrus neuron loss and mossy fiber sprouting
      are not primary epileptogenic mechanisms in this animal model.

PMID- 15973681
TI  - Development of neurons and fibers containing calcium binding proteins in the
      pallial amygdala of mouse, with special emphasis on those of the basolateral
      amygdalar complex.
AB  - We studied the development of neurons and fibers containing calbindin,
      calretinin, and parvalbumin in the mouse pallial amygdala, with special emphasis
      on those of the basolateral amygdalar complex. Numerous calbindin-immunoreactive
      (CB+) cells were observed in the incipient basolateral amygdalar complex and
      cortical amygdalar area from E13.5. At E16.5, CB+ cells became more abundant in
      the lateral and basolateral nuclei than in the basomedial nucleus, showing a
      pattern very similar to that of gamma-aminobutyric acid (GABA)ergic neurons. Many
      CB+ cells observed in the pallial amygdala appeared to originate in the anterior
      entopeduncular area/ganglionic eminences of the subpallium. The density of CB+
      cells gradually increased in the pallial amygdala until the first postnatal week
      and appeared to decrease later, coinciding with the postnatal appearance of
      parvalbumin cells and raising the possibility of a partial phenotypic shift.
      Calretinin (CR) immunoreactivity could be observed in a few cells and fibers in
      the pallial amygdala at E14.5, and by E16.5 it became a good marker of the
      different nuclei of the basolateral amygdalar complex. Numerous CB+ and CR+
      varicosities, part of which have an intrinsic origin, were observed in the
      basolateral amygdalar complex from E16.5, and some surrounded unstained perikarya
      and/or processes before birth, indicating an early formation of inhibitory
      networks. Each calcium binding protein showed a distinct spatiotemporal
      expression pattern of development in the mouse pallial amygdala. Any alteration
      in the development of neurons and fibers containing calcium binding proteins of
      the pallial amygdala may result in important disorders of emotional and social
      behavior.

PMID- 15973682
TI  - Functional impact of primary visual cortex deactivation on subcortical target
      structures in the thalamus and midbrain.
AB  - The functional relationships between the primary visual cortex and its major
      subcortical target structures have long been a subject of interest. We studied
      these relationships by using localized cooling deactivation to silence portions
      of primary visual cortex and measuring 2-deoxyglucose (2DG) uptake to assess
      neural activity in subcortical and midbrain targets. We focused analysis on the
      largest subcortical targets of primary visual cortex: the superior colliculus
      (SC), the dorsal lateral geniculate nucleus of the thalamus (dLGN), and the
      lateral division of the lateral posterior nucleus of the thalamus (LPL). We found
      that localized cooling of different regions of primary visual cortex caused
      specific decreases in 2DG uptake in target structures such that the location of
      2DG decrease varied according to joint retinotopy, and the magnitude of the
      decreases in target structures was associated with the amount of cooled cortex.
      In addition, we found that the impact of cortical cooling was more profound on
      the SC than on the dLGN. The functional impact of cortical deactivations on the
      LPL was weak for small deactivations but approximated the impact on the SC when
      deactivations were large. We discuss these findings in terms of neural circuits
      and in terms of drivers and modulators.

PMID- 15973683
TI  - Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.
AB  - Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell
      types and support extension of olfactory axons (OAs) within the olfactory
      pathway. OEGs are thought to exclude OAs from contact with all other cells
      between the olfactory epithelium and the glomerulus of the olfactory bulb. These
      properties have lead to testing to determine whether OEGs support axonal growth
      following transplantation. The cellular interactions of transplanted OEGs will
      probably resemble those that occur within the normal pathway where interactions
      between OEGs and fibroblasts are prominent. No previous primate studies have
      focused on these interactions, knowledge of which is important if clinical
      application is envisioned. We describe the detailed intercellular interactions of
      OAs with supporting cells throughout the olfactory epithelium, the lamina
      propria, the fila olfactoria, and the olfactory nerve layer by using transmission
      electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment
      and variations of the endo- and perineurium formed by olfactory nerve fibroblasts
      are described. OAs mainly interacted with horizontal basal cells, OEGs, and
      astrocytes. At both transitional ends of the pathway seamless intercellular
      interactions were observed, and fibroblast processes were absent. Perineurial
      cells produced surface basal lamina; however, endoneurial, epineurial, and
      meningeal fibroblasts did not. Perineurial cells contained intermediate filaments
      and were distinct from other fibroblasts and meningeal cells. OAs had direct
      contacts with astrocytes near the glia limitans. The properties of OEGs differed
      depending on whether astrocytic or fibroblastic processes were present. This
      indicates the importance of the cellular milieu in the structure and function of
      OEGs in primates.

PMID- 15973684
TI  - Subcellular localization of the dopamine D2 receptor and coexistence with the
      calcium-binding protein neuronal calcium sensor-1 in the primate prefrontal
      cortex.
AB  - Structures of the cerebral cortex expressing the D2 dopamine receptor subtype
      (D2) are important sites of action of antipsychotic drugs. It has also been
      repeatedly suggested that the prefrontal cortex plays a significant role in
      neuropsychiatric disorders, including schizophrenia. Here, by using single and
      double immunohistochemical techniques with electron microscopy, we investigated
      in the primate prefrontal cortex the ultrastructural localization of D2 and we
      compared it with that of the neuronal calcium sensor-1 (NCS-1), a neuron-specific
      calcium-binding and D2-interacting protein. D2 immunoreactivity, revealed with
      preembedding immunoperoxidase in single labeling and with preembedding immunogold
      for double labeling, was localized in cell bodies with ultrastructural
      characteristics of both neurons and astroglia. D2 was localized in pre- and
      postsynaptic structures, including spines and dendrites, and in both excitatory-
      and inhibitory-like axon terminals. Immunogold labeling revealed peri- and
      extrasynaptic localization of D2 in postsynaptic structures, whereas
      extrasynaptic labeling was typically found in boutons. NSC-1 immunoreactivity was
      abundant in pre- and postsynaptic structures, in which it was also colocalized
      with D2. With the present strategy (that has high resolution but relatively
      limited sensitivity), NSC-1 was observed in about 10% of the D2-immunopositive
      spines and in a lower proportion of D2-immunopositive dendrites and boutons. The
      data demonstrate the localization of D2 in pre- and postsynaptic as well as extra
      and perisynaptic structures of the primate prefrontal cortex. The data also show
      the coexistence of NCS-1 and D2 at the ultrastructural level. The latter finding
      suggests a role for NCS-1 in desensitization of D2 in the prefrontal cortex.

PMID- 15973685
TI  - Differential distribution of hypocretin (orexin) and melanin-concentrating
      hormone in the goldfish brain.
AB  - The orexigenic peptides hypocretin (orexin) and melanin-concentrating hormone
      (MCH) are involved in the control of food intake and in other homeostatic
      functions including sleep and arousal. In this article we study the distribution
      of these peptides in the brain of the goldfish (Carassius auratus), focusing on
      those regions particularly related to feeding, sleep, and arousal. Although the
      general distribution of these peptides in goldfish shows many similarities to
      those described previously in other species, we observed some noteworthy
      differences. As in other vertebrates, the peptidergic somata lie in the
      anterolateral hypothalamus. In goldfish, both hypocretin and MCH immunoreactive
      cell bodies project fibers to the ventral telencephalon, thalamus, and
      hypothalamus. At mesencephalic levels fibers reach the deep layers of the optic
      tectum and also course sparsely through the mesencephalic tegmentum. In contrast
      to the strong innervation of locus coeruleus and raphe in mammal, the MCH and
      hypocretin systems in goldfish barely innervate these aminergic populations
      related to the regulation of sleep and arousal. MCH, but not hypocretin,
      immunoreactive fibers terminate substantially in the sensory layer of the vagal
      gustatory lobe of goldfish, while both peptidergic systems distribute to the
      primary visceral sensory areas of the medulla and pons. The strong involvement of
      these peptidergic systems with the hypothalamus and general visceral nuclei, but
      not with locus coeruleus or raphe nuclei support the view that these peptides
      originally played a role in regulation of energy balance and evolved secondarily
      to influence sleep-wakefulness systems in amniote vertebrates.

PMID- 15973686
TI  - Bovine ICM derived cells express the Oct4 ortholog.
AB  - The goal of this study was to define conditions for the successful isolation of
      embryonic stem cells from bovine blastocysts. Expression of the Pit-Oct-Unc (POU)
      transcription factor Oct4 was employed to monitor the pluripotent status of
      cultured cells. No expression of the previously identified bovine Oct4 pseudogene
      was found, and transcription of the Oct4 ortholog correlated with the
      proliferative potential of bovine ICM derived cells. Two methods to isolate
      pluripotent inner cell mass were compared; 90% of trypsin isolated ICMs formed
      growing cultures, whereas only 12%-23% of the ICMs isolated by immunosurgery
      attached and grew. Colony formation from complete blastocysts was 55%. The bovine
      ICM derived cells could be grown for 4-7 passages. However, Oct4 transcripts were
      only present in the primary cultures, indicating that the initial culture period
      of bovine ICM derived cells is critical and needs to be optimized to yield true
      ES cells. In contrast to bovine ICMs, murine ICMs yielded rapidly growing cells,
      which proliferated for more than 60 passages.

PMID- 15973687
TI  - Effects of FSH receptor deletion on epididymal tubules and sperm morphology,
      numbers, and motility.
AB  - Follicle stimulating hormone (FSH) interacts with its cognate receptor (R) on
      Sertoli cells within the testis and plays an important role in the maintenance of
      spermatogenesis. Male FSH-R knockout (FORKO) mice show fewer Sertoli cells and
      many that are structurally abnormal and as a consequence fewer germ cells. Lower
      levels of serum testosterone (T) and androgen binding protein (ABP) also occur,
      along with reduced fertility. To assess the effects of FSH-R depletion as an
      outcome of testicular abnormalities, sperm from the cauda epididymidis were
      counted and examined ultrastructurally. As reduced fertility may also reflect
      changes to the epididymis, the secondary responses of the epididymis to lower T
      and ABP levels were also examined by comparing differences in sizes of epididymal
      tubules in various regions of FORKO and wild type (WT) mice. Sperm motility was
      evaluated in FORKO mice and compared to that of WT mice by computer assisted
      sperm analysis (CASA). Quantitatively, the data revealed that epithelial areas of
      the caput and corpus epididymidis were significantly smaller in FORKO mice
      compared to WT mice. Cauda epididymal sperm counts in FORKO mice were also much
      lower than in WT mice. This resulted in changes to 9 out of 14 sperm motility
      parameters, related mostly to velocity measures, which were significantly lower
      in the FORKO mice. The greatest change was observed relative to the percent
      static sperm, which was elevated by 20% in FORKO mice compared to controls. EM
      analyses revealed major changes to the structure of the heads and tails of cauda
      luminal sperm in FORKO mice. Taken together these data suggest a key role for the
      FSH receptor in maintaining Sertoli cells to sustain normal sperm numbers and
      proper shapes of their heads and tails. In addition, the shrinkage in epididymal
      epithelial areas observed in FORKO mice likely reflect direct and/or indirect
      changes in the functions of these cells and their role in promoting sperm
      motility, which is noticeably altered in FORKO mice.

PMID- 15973688
TI  - Facilitated primary coronary intervention with abciximab and very low dose of
      alteplase during off-hours compared with direct primary intervention during
      regular hours.
AB  - In patients with acute myocardial infarction (AMI), the off-hour presentation is
      one of the major determinants of door-to-balloon delay. Moreover, the nighttime
      presentation is associated with increased mortality after primary coronary
      intervention (PCI). The prompt starting of a therapy able to start recanalization
      of the infarct-related artery before intervention might improve the results of
      off-hour primary PCI. We compared the outcome of 212 consecutive patients with
      AMI undergoing either direct or facilitated PCI according to the hour of
      presentation. Patients arriving off-hours were pretreated with alteplase (20 mg)
      and abciximab and underwent facilitated PCI. Patients presenting on-hours
      underwent direct PCI. A basal Thrombolysis in Myocardial Infarction (TIMI) flow
      grade 3 was observed in 1.0% of patients undergoing direct PCI and in 44% of
      patients undergoing facilitated PCI (P = 0.001). More patients starting PCI with
      a TIMI 3 flow achieved a postinterventional fast TIMI frame count (72.0% vs.
      38.8% direct PCI group vs. 34.9% facilitated PCI group with basal TIMI 0-2; P =
      0.001) and a TIMI perfusion grade 3 (66.0% vs. 38.8% direct PCI group vs. 39.7%
      facilitated PCI group with basal TIMI 0-2; P = 0.004). Preinterventional TIMI
      flow grade 3 was associated with a higher gain in left ventricular ejection
      fraction at 1 month (10.9% +/- 6.4% vs. 7.0% +/- 9.6% direct PCI group vs. 6.1%
      +/- 6.0% facilitated PCI group with basal TIMI 0-2; P = 0.005). No significant
      difference was observed in major bleedings, although there was a trend toward a
      higher risk in the facilitated PCI group. Patients in the facilitated PCI group
      achieving a basal TIMI 3 flow showed improved myocardial reperfusion and better
      left ventricular function recovery. Bleeding complications associated with
      combination therapy remained an important concern.

PMID- 15973689
TI  - Effect of hybrid layer on stress distribution in a premolar tooth restored with
      composite or ceramic inlay: an FEM study.
AB  - The aim of this finite elemental stress analysis study was to evaluate the effect
      of hybrid layer on distribution and amount of stress formed under occlusal
      loading in a premolar tooth restored with composite or ceramic inlay. The
      mandibular premolar tooth was selected as the model based on the anatomical
      measurements suggested by Wheeler. The analysis is performed by using a Pentium
      II IBM compatible computer with the SAP 2000 structural analysis program. Four
      different mathematical models including the following structures were evaluated:
      1) composite inlay, adhesive resin, and tooth structure; 2) composite inlay,
      adhesive resin, hybrid layer, and tooth structure; 3) ceramic inlay, adhesive
      resin, and tooth structure; 4) ceramic inlay, adhesive resin, hybrid layer, and
      tooth structure. Loading was applied from the occlusal surface of the
      restoration, and shear stresses under loading were evaluated. The findings were
      drawn by the Saplot program, and the results were analyzed by graphical
      comparison method. The output indicated that the hybrid layer acts as a stress
      absorber in models 2 and 4. The hybrid layer has also changed mathematical values
      of stress on cavity floors in both restoration types. Ceramic inlay collected the
      stress inside the body of the material, but the composite inlay directly
      transferred the stress through dental tissues. As a result, it was concluded that
      the hybrid layer has an effect on stress distribution under loading in a premolar
      tooth model restored with composite or ceramic inlay.

PMID- 15973690
TI  - Permeability of adhesive resin films.
AB  - The purpose of this study was to quantify the permeability of adhesive resin
      films to water by measuring convective flow across thin films. Cured resin films
      were prepared with the use of five commercially available adhesive resins and an
      experimental resin. Two types of resin films were prepared from solvated
      comonomer blends within each product; resin films made before or after
      evaporation of solvent (10 s of drying with air-syringe). The permeability of the
      resin films was measured 30 min or 24 h after polymerization by placing the films
      in a split-chamber device. Fluid filtration rate through the resin films was
      measured with the use of 20 cm of water pressure. Osmotically induced water
      movement was measured by applying hypertonic aqueous solutions of CaCl2 or HEMA
      to the resin films. The results showed that evaporation of solvent before
      polymerization reduced the permeability of adhesive resin films, compared to
      permeabilities obtained without solvent evaporation. The cured adhesive resin
      films were all permeable to water, but to varying degrees.

PMID- 15973692
TI  - Specification of embryonic axis and mosaic development in ascidians.
AB  - Setting up future body axes is the first important event before and at the
      beginning of embryogenesis. The ascidian embryo is a classic model that has been
      used to gain insight into developmental processes for over a century. This review
      summarizes advances made in this decade in our understanding of the developmental
      processes involved in the specification of the embryonic axes and cell fates
      during early ascidian embryogenesis. Maternal factors, including mRNAs, are
      translocated to specific regions of the egg by cytoplasmic and cortical
      reorganization, so-called ooplasmic segregation, and specify the animal-vegetal
      axis and the one perpendicular to it, which is defined as the anteroposterior
      axis in ascidians. Some postplasmic/PEM RNAs that are anchored to cortical
      endoplasmic reticulum are brought to the future posterior pole of fertilized
      eggs, and play crucial roles in posterior development. Following specification of
      the animal-vegetal axis, nuclear localization of beta-catenin takes place in the
      vegetal blastomeres; this occurrence is important for the acquisition of the
      vegetal character of the blastomeres in later development. Positioning of these
      maternal factors lead to subsequent cell interactions and zygotic gene expression
      responsible for axis establishment and for cell fate specification. We describe
      how endoderm blastomeres in the vegetal pole region emanate inductive signals
      mainly attributable to fibroblast growth factor. Marginal blastomeres next to
      endoderm blastomeres respond differently in ways that are determined by intrinsic
      competence factors. Expression patterns of developmentally important genes,
      including key transcription factors of each tissue type, are also summarized.

PMID- 15973691
TI  - Effect of surface treatment on the shear bond strength of three resin cements to
      a machinable feldspatic ceramic.
AB  - The aim of this study was to evaluate the shear bond strength of three resin
      cements to Vita Mark II ceramics under different pretreatments of the ceramic
      surface and to examine whether simplified pretreatment procedures would result in
      satisfying results compared to the state of the art. RelyX Unicem (RXU), Calibra
      (CAL), and Variolink II (VAR) were used as resin cements and bonded to machine
      milled feldspatic disks, pretreated in five different ways. (1) no pretreatment
      of the ceramic surface; (2) surface etched with hydrofluoric acid (HF); (3)
      ceramic surface silanized; (4) ceramic surface etched (HF) and silanized, (5)
      ceramic surface etched (HF), silanized, and covered with Heliobond. The shear
      bond strengths were measured initially, after 5000 and 10,000 thermocycles (TC).
      After 10,000 TC for CAL only procedure 5 resulted in a reliable adhesion median
      value of 10.7 MPa. VAR showed median values of 24.6, 17.2, and 18.1 MPa for
      pretreatments 5, 3, and 4, respectively. RXU performed 25.9, 22.0, and 11.0 MPa
      for procedures 5, 4, and 3, respectively. For procedure 2, RXU revealed the
      significantly highest value with 15.4 MPa (U-test, p = 0.05). Only RXU-luted
      specimens of procedure 1 survived the 10,000 thermocycles. The results revealed
      that a simplification of the ceramic pretreatment for VAR and RXU might be
      possible.

PMID- 15973693
TI  - Professional and economic factors affecting access to mammography: a crisis
      today, or tomorrow? Results from a national survey.
AB  - BACKGROUND: Objective data and anecdotal reports have suggested that access to
      mammography may be declining because of facility closures and difficulty in
      recruiting and retaining radiologists and radiologic technologists. To gain
      insight into the practice patterns, use of emerging technologies, and concerns of
      breast imagers in current practice, the Society of Breast Imaging (SBI) conducted
      a national survey of breast imaging practices in the U.S. METHODS: Between
      October 2003 and April 2004, the SBI conducted a survey of the SBI membership
      database, and received completed surveys from 575 breast imaging practices in the
      U.S. Responses to the survey regarding practice characteristics, the utilization
      of standard and emerging technologies, staffing, malpractice, finance, and morale
      were analyzed. RESULTS: Job vacancies for radiologists who read mammograms were
      reported in 163 practices (29%), 59 of which (10%) had 2 or more openings. A
      higher proportion of practices with job openings had long appointment waiting
      times for asymptomatic women when compared with fully staffed practices. Unfilled
      fellowship positions also were common, with 41 of 65 practices that offer
      fellowships reporting 47 openings. Among 554 responding practices, 55% reported
      that someone in their practice was sued because of a mammography related case
      within the past 5 years, and 50% of practices reported that the threat of
      lawsuits made radiologist staffing "moderately" or "a lot" more difficult. Of 521
      responding practices, 35% reported financial losses in 2002. One in 5 respondents
      reported that they would prefer to spend less time in mammography, and fewer than
      1 in 3 would recommend a breast imaging fellowship to a relative or friend.
      Emerging technologies, such as breast magnetic resonance imaging and screening
      ultrasound, currently are being performed in many practices. CONCLUSIONS: The
      survey results provide support for anecdotal reports that breast imaging
      practices face significant challenges and stresses, including shortages of key
      personnel, a lack of trainees, malpractice concerns, financial constraints,
      increased workload due to emerging technologies, low appeal of breast imaging as
      a career specialty, and the steady rise in the population of women of screening
      age.

PMID- 15973694
TI  - Modulation of gene expression in neonatal rat cardiomyocytes by surface
      modification of polylactide-co-glycolide substrates.
AB  - Myocardial tissue engineering presents a potential treatment option for heart
      disease. Cardiomyocytes isolated at various stages of development retain the
      ability to form contractile networks in vitro, which suggests that it should be
      possible to reconstitute viable myocardium given the appropriate architecture,
      stimuli, and cardiomyogenic cell source. This study investigates the effects of
      modifying substrate surface energy (by plasma etching) and protein coating (by
      fibronectin adsorption) on neonatal rat ventricular myocyte (NRVM) function.
      Primary NRVMs were cultured for 96 h on modified and control films of a common
      degradable polymer, polylactide-co-glycolide. Cultures were analyzed for cell
      spreading, protein content, and mRNA expression of atrial natriuretic factor and
      beta-myosin heavy chain. The results demonstrate that NRVMs cultured on etched
      films significantly increased in spreading, myofibril development, protein
      content, and gene expression of atrial natriuretic factor and beta-myosin heavy
      chain compared with unetched films, and that this surface energy effect is
      overwhelmed by the addition of fibronectin. Conclusions from this study are that
      surface energy and protein adsorption influence the gene expression of adherent
      NRVMs, and may be important for modulating the function of engineered myocardium.

PMID- 15973695
TI  - Collagen-carbon nanotube composite materials as scaffolds in tissue engineering.
AB  - Carbon nanotubes (CNT) are attractive for use in fiber-reinforced composite
      materials due to their very high aspect ratio, combined with outstanding
      mechanical and electrical properties. Composite materials comprising a collagen
      matrix with embedded CNT were prepared by mixing solubilized Type I collagen with
      solutions of carboxylated single-walled carbon nanotubes (SWNT) at concentrations
      of 0, 0.2, 0.4, 0.8, and 2.0 weight percent. Living smooth muscle cells were
      incorporated at the time of collagen gelation to produce cell-seeded collagen-CNT
      composite matrices. Constructs containing 2.0 wt % CNT exhibited delayed gel
      compaction, relative to lower concentrations that compacted at the same rate as
      pure collagen controls. Cell viability in all constructs was consistently above
      85% at both Day 3 and Day 7, whereas cell number in CNT-containing constructs was
      lower than in control constructs at Day 3, though statistically unchanged by Day
      7. Scanning electron microscopy showed physical interactions between CNT and
      collagen matrix. Raman spectroscopy confirmed the presence of CNT at the expected
      diameter (0.85-1.30 nm), but did not indicate strong molecular interactions
      between the collagen and CNT components. Such collagen-CNT composite matrices may
      have utility as scaffolds in tissue engineering, or as components of biosensors
      or other medical devices.

PMID- 15973696
TI  - Cell tracking velocimetry as a tool for defining saturation binding of
      magnetically conjugated antibodies.
AB  - BACKGROUND: Continuous flow immunomagnetic separation is an attractive
      alternative to current batch mode immunomagnetic separation methods because it is
      capable of high sorting speeds at mild cell conditions, and grants the operator
      better control of separation process. The control of the separation is dependent
      on knowledge of the amount of magnetic label attached to the cell (magnetic
      labeling intensity), however. Determination of the magnetic labeling is
      accomplished by measuring cell magnetophoretic mobility using a newly developed
      technique of Cell Tracking Velocimetry (CTV). METHODS: Flow cytometry was used to
      define the antibody binding characteristics of a fluorescently tagged primary
      antibody. Subsequently, CTV was used to measure antibody-binding characteristics
      of a magnetically tagged secondary antibody. RESULTS: The results of this study
      show that CTV is capable of providing valuable information concerning the cell
      labeling by magnetically tagged antibodies. It was demonstrated that the
      magnetically conjugated antibody binding curve exhibits the same exponential
      increase to saturation characteristics as that seen with the fluorescently tagged
      antibody. Further, it was shown that the intensity of the secondary magnetic
      labeling is directly proportional to the intensity of the primary fluorescent
      label. CONCLUSIONS: CTV is an accurate tool for evaluation of magnetically
      conjugated antibodies. The ability to determine the intensity of magnetic
      labeling is necessary for the development of continuous flow immunomagnetic
      separations based on cell magnetophoresis.

PMID- 15973697
TI  - Performance analysis of a dual-buffer architecture for digital flow cytometry.
AB  - BACKGROUND: Most current commercial flow cytometers employ analog circuitry to
      provide feature values describing the pulse waveforms produced from suspended
      cells and particles. This restricts the type of features that can be extracted
      (typically pulse height, width, and integral) and consequently places a limit on
      classification performance. In previous work, we described a first-generation
      digital data acquisition and processing system that was used to demonstrate the
      classification advantages provided by the extraction of additional waveform
      features. An improved version of the system is discussed in this paper, focusing
      on dual-buffering to ensure increased pulse capture. A mathematical model of the
      system is also presented for performance analysis. METHODS: The second-generation
      system incorporates fast digitization of analog pulse waveforms, instantaneous
      pulse detection hardware, and a novel dual-buffering scheme. A mathematical model
      of the system was developed to theoretically compute the capture-rate
      performance. RESULTS: The capture rate of the system was theoretically analyzed
      and empirically measured. Under typical conditions, a capture rate of 8,000
      pulses/s was experimentally achieved. CONCLUSIONS: Based on these results, the
      dual-buffer architecture shows great potential for use in flow cytometry.

PMID- 15973698
TI  - Improving the biosafety of cell sorting by adaptation of a cell sorting system to
      a biosafety cabinet.
AB  - BACKGROUND: The jet-in-air cell sorters currently available are not very suitable
      for sorting potentially biohazardous material under optimal conditions because
      they do not protect operators and samples as recommended in the guidelines for
      safe biotechnology. To solve this problem we have adapted a cell sorting system
      to a special biosafety cabinet that satisfies the requirements for class II
      cabinets. With aid of this unit, sorting can be performed in conformance with the
      recommendations for biosafety level 2. METHODS: After integrating a modified
      fluorescence-activated cell sorter (FACS) Vantage into a special biosafety
      cabinet, we investigated the influence of the laminar air flow (LAF) inside the
      cabinet on side stream stability and the analytical precision of the cell sorter.
      In addition to the routine electronic counting of microparticles, we carried out
      tests on the containment of aerosols, using T4 bacteriophage as indicators, to
      demonstrate the efficiency of the biosafety cabinet for sorting experiments
      performed under biosafety level 2 conditions. RESULTS: The experiments showed
      that LAF, which is necessary to build up sterile conditions in a biosafety
      cabinet, does not influence the conditions for side stream stability or the
      analytical precision of the FACS Vantage cell sorting system. In addition, tests
      performed to assess aerosol containment during operation of the special biosafety
      cabinet demonstrated that the cabinet-integrated FACS Vantage unit (CIF)
      satisfies the conditions for class II cabinets. In the context of gene transfer
      experiments, the CIF facility was used to sort hematopoietic progenitor cells
      under biosafety level 2 conditions. CONCLUSIONS: The newly designed biosafety
      cabinet offers a practical modality for improving biosafety for operators and
      samples during cell sorting procedures. It can thus also be used for sorting
      experiments with genetically modified organisms in conformance with current
      biosafety regulations and guidelines.

PMID- 15973699
TI  - Multicentre evaluation of stable reference whole blood for enumeration of
      lymphocyte subsets by flow cytometry.
AB  - BACKGROUND: Clinical indications for lymphocyte subset enumeration by flow
      cytometry include monitoring of disease progression and timing of therapeutic
      intervention in infection with human immunodeficiency virus. Until recently
      international standardisation has not been possible due to a lack of suitable
      stable reference material. METHODS: This study consisted of two trials of a
      stabilised whole blood preparation. Eleven participants were sent two standard
      protocols for staining plus gating strategy and asked to report absolute counts
      for lymphocyte subsets. RESULTS: No significant difference was detected between
      the two methods when results from the two assays and all partners were pooled.
      Significant differences in results from the different partners were observed.
      However, representative mean counts were obtained for geometric means, geometric
      coefficient of variation, and 95% confidence interval for CD3 910 cells/mul, 9%,
      and 888 to 933, respectively), CD4 (495 cells/mul, 12%, and 483 to 507), and CD8
      (408 cells/mul, 13%, and 393 to 422). CONCLUSION: We have introduced a stabilised
      blood preparation and a well-characterized biological standard. The availability
      of this reference material greatly simplifies the validation of new techniques
      for CD4(+) T-cell enumeration and the expansion of external quality assurance
      programmes for clinical laboratories, including those that operate in resource
      restricted environments. (c) 2005 Wiley-Liss, Inc.

PMID- 15973700
TI  - Flow cytometric immunophenotypic profiles of mature gamma delta T-cell
      malignancies involving peripheral blood and bone marrow.
AB  - BACKGROUND: In this study we compared clinical findings with flow cytometric
      immunophenotypic results in a series of patients with aggressive and indolent
      gamma delta T-cell malignancies with peripheral blood and/or bone marrow
      involvement. METHODS: Gamma delta T-cell malignancies were detected based on flow
      cytometric demonstration of an abnormal T-cell population staining positive with
      T-cell receptor gamma delta and confirmed by morphologic and clinical reviews.
      Clinical data were obtained through chart review and discussion with the
      patients' physicians. RESULTS: Blood or bone marrow involvement was present in
      all patients. Hepatosplenic and cutaneous gamma delta T-cell lymphomas had an
      aggressive clinical course, whereas the gamma delta T-cell large granular
      lymphocyte (LGL) leukemias had an indolent course. Expressions of CD5, CD8, CD16,
      and CD57 differed in gamma delta T-cell LGL leukemia compared with hepatosplenic
      and cutaneous gamma delta T-cell lymphomas. CONCLUSIONS: Gamma delta T-cell
      malignancies have a poor prognosis with the exception of gamma delta T-cell LGL
      leukemia (indolent process). Because CD57 expression is specific for gamma delta
      T-cell LGL leukemias, expression of this antigen may be associated with a more
      indolent clinical course. Because cutaneous gamma delta T-cell lymphoma can
      present with peripheral blood involvement, flow cytometric evaluation of
      peripheral blood is important in staging these patients.

PMID- 15973701
TI  - Isolation and comparative expression analysis of the Myc-regulatory proteins
      Mad1, Mad3, and Mnt during Xenopus development.
AB  - The Myc-Max-Mad network of transcription factors plays an essential role in many
      cellular processes such as proliferation, differentiation, and apoptosis. The Mad
      proteins heterodimerize with Max, function as transcriptional repressors, and are
      capable of antagonizing the transforming activity of Myc. We report on the
      isolation of Xmad1, Xmad3, and Xmnt, novel Xenopus genes belonging to the Mad
      family. We also describe their temporal and spatial expression patterns during
      Xenopus embryogenesis. Xmad1 expression is found primarily in cells that have
      undergone terminal differentiation including the notochord, floor plate, and
      cement gland. Xmad3 transcripts are expressed broadly throughout the central
      nervous system and the eye, starting at neurula stages. In contrast, Xmnt
      expression in the CNS was localized anteriorly and, in addition, is present in
      the migrating neural crest cells. This study demonstrates the Mads are expressed
      in specific and mostly nonoverlapping patterns, suggesting distinct roles during
      embryogenesis.

PMID- 15973702
TI  - Hepatic B-cell non-Hodgkin's lymphoma of MALT type in the liver explant of a
      patient with chronic hepatitis C infection.
AB  - B-cell non-Hodgkin's lymphoma (B-NHL) is a well-documented complication of
      hepatitis C virus (HCV) infection. Marginal zone (mucosa-associated lymphoid
      tissue; MALT) lymphomas constitute a less common type of B-NHL. In this article,
      we report a case of liver MALT in a cirrhotic patient, incidentally discovered
      after liver transplantation (LT). We discuss pertinent diagnostic and management
      strategies in this clinical setting.

PMID- 15973703
TI  - Ischemia-reperfusion of rat liver modulates hepcidin in vivo expression.
AB  - The recently identified acute-phase response antimicrobial peptide hepcidin has
      been postulated to maintain iron homeostasis by modulating iron absorption at
      both the intestinal and macrophage levels. Hepcidin has also been reported to be
      responsible for anemia associated with chronic inflammatory diseases, and in
      anemia in patients with hepatic adenomas. Since Kupffer cells are known to be the
      primary contributor to early-phase ischemia-reperfusion injury in the liver and
      iron is known to modulate Kupffer cell production of proinflammatory cytokine and
      reactive oxygen species, we investigated hepcidin in vivo expression in the well
      established rat partial-liver ischemia-reperfusion model. We found that both
      liver ischemia alone and liver ischemia-reperfusion significantly induced serum
      and liver hepcidin levels. Furthermore, currently proposed mediators of in vivo
      hepcidin expression, such as interleukin-6, signal transducers and activators of
      transcription-family transducers, and CCAAT/enhancing binding protein-alpha do
      not appear to modulate hepcidin expression in the liver ischemia-reperfusion
      acute inflammatory model. In this study we report the first in vivo evidence of
      liver ischemia and liver ischemia-reperfusion modulation of hepcidin expression.
      In conclusion, in the well-characterized liver ischemia-reperfusion model of
      acute inflammation, mechanism(s) other than interleukin-6 signal transduction via
      signal transducers and activators of transcription-3 may be responsible for
      hepcidin induction.

PMID- 15973705
TI  - Hepatitis C, Helicobacter, lymphoma...and liver transplantation.

PMID- 15973704
TI  - Identification of new netrin family members in zebrafish: developmental
      expression of netrin 2 and netrin 4.
AB  - Netrin 1 is a diffusible factor that attracts commissural axons to the floor
      plate of the spinal cord. Recent evidence indicates that Netrin 1 is widely
      expressed and functions in the development of multiple organ systems. In mammals,
      there are three genes encoding Netrins, whereas in zebrafish, only the Netrin 1
      orthologs netrin 1a and netrin 1b have been identified. Here, we have cloned two
      new zebrafish Netrins, netrin 2 and netrin 4, and present a comparative sequence
      and expression analysis. Despite significant sequence similarity with netrin
      1a/netrin 1b, netrin 2 displays a unique expression pattern. Netrin 2 transcript
      is first detected in the notochord and in developing somites at early
      somitogenesis. By late somitogenesis, netrin 2 is expressed in the fourth
      rhombomere and is subsequently expressed in the hindbrain and otic vesicles. In
      contrast, netrin 4 is detected only at very low levels during early development.
      The nonoverlapping expression patterns of these four Netrins suggest that they
      may play unique roles in zebrafish development.

PMID- 15973706
TI  - A critical analysis to a critical analysis: breaking the circle of organ
      allocation in the United States.

PMID- 15973707
TI  - Venovenous bypass in orthotopic liver transplantation: time for a rethink?

PMID- 15973708
TI  - Right hepatic lobe donation adversely affects donor life insurability up to one
      year after donation.
AB  - There are no data regarding hepatic lobe donation effects on donor life
      insurability. Two investigators called 10 agents of 10 different large life
      insurance companies. One investigator gave a fictitious profile: Caucasian man,
      33 years old, nonsmoker, without medical problems (control profile [CP]). The
      other investigator used the same profile with a history of uncomplicated right
      lobe donation 12 months earlier (donor profile [DP]). Investigators asked for
      premium quotes on a $100,000 term life policy. No medical testing or record
      review was allowed. Investigators were blinded to the results of each other's
      calls. Agents were unaware of the study. We documented underwriting decisions,
      premiums quoted, stipulations, number of phone calls, and phone time. All 10
      companies would pursue underwriting CP at their lowest, "preferred" rate. Five
      would do the same for DP. Two might underwrite DP at a more expensive "standard"
      rate, but a "preferred" rate would be less likely. One would underwrite DP at the
      "standard" rate; one would not underwrite DP. One agent did not return follow-up
      calls (DP insurability < CP, P = 0.04). Mean quoted premiums were lower for CP
      vs. DP ($189/yr. vs. $202/yr., P = 0.56). Median number of phone calls required
      was 1 for CP and 3 for DP (P = 0.01). Mean telephone minutes were 4.2 for CP and
      8.0 for DP (P = 0.004). In conclusion, right hepatic lobe donation decreases life
      insurability 1 year after uncomplicated donation. Donors can expect some
      increased difficulty obtaining life insurance, but they should find a company
      willing to pursue underwriting. The premium paid may be slightly higher.

PMID- 15973709
TI  - Life insurability of the right lobe live liver donor.

PMID- 15973710
TI  - Impact of pretransplantation transarterial chemoembolization on survival and
      recurrence after liver transplantation for hepatocellular carcinoma.
AB  - The actual impact of transarterial chemoembolization before liver transplantation
      (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is
      not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were
      evaluated for LT. Among these 479 patients, this case-control study included 100
      patients who received transarterial chemoembolization before LT (TACE group) and
      100 control patients who did not receive chemoembolization (no-TACE group).
      Patients and controls were matched for the pre-LT tumor characteristics, the
      period of transplantation, the time spent on the waiting list, and pre- and
      posttransplantation treatments. Kaplan-Meier estimates were calculated 5 years
      after LT and were compared with the log-rank test. The mean waiting time before
      LT was 4.2 +/- 3.2 months in the TACE group and 4.3 +/- 4.4 months in the no-TACE
      group. The median number of TACE procedures was 1 (range: 1-12). Demographic
      data, median alpha-fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively),
      and pre- and post-LT morphologic characteristics of the tumors did not differ in
      the TACE and no-TACE groups. Overall 5-year survival was 59.4% with TACE and
      59.3% without TACE (ns). Survival rates did not differ significantly between the
      two groups with respect to the time on the waiting list, the tumor diameter, or
      the type of TACE (selective or nonselective). In the TACE group, 30 patients had
      tumor necrosis > or =80% on the liver explant with a 5-year survival rate of
      63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion,
      with a mean waiting period of 4.2 months and 1 TACE procedure, pre-LT TACE does
      not influence post-LT overall survival and disease-free survival.

PMID- 15973711
TI  - "All-in-one" imaging protocols for the evaluation of potential living liver
      donors: comparison of magnetic resonance imaging and multidetector computed
      tomography.
AB  - In order to compare the performance of "all-in-one" magnetic resonance imaging
      (MRI) and "all-in-one" multidetector computed tomography (MDCT) in the preharvest
      evaluation 25 potential living donors underwent both MRI and MDCT. MRI was
      performed on a high-performance 1.5-T scanner, computed tomography (CT) on a 4
      row multidetector-scanner. Both scan protocols included angiography of the
      arterial and venous hepatic systems. CT additionally included infusion of a
      biliary contrast agent. Data analysis was performed by 4 reviewers, based on
      source images, multiplanar reformats, and three-dimensional (3D) postprocessing.
      Determination of image quality was based on a 4-point image quality rating (IQR)
      scale, ranging from 1 = nondiagnostic to 4 = excellent. Preoperative and
      intraoperative (n = 13) findings were correlated. Magnetic resonance (MR)
      examinations were generally well tolerated. Within the CT scan, 2 candidates
      presented moderate adverse reaction to the biliary contrast agent. MRI and CT
      showed the same benign parenchymal lesions (IQR MR: 3.7; IQR CT: 3.4).
      Determination of liver volumes was easier based on CT (IQR MR: 3.3; IQR CT: 3.6).
      Magnetic resonance angiography (MRA) revealed 10 variants of the arterial liver
      supply (IQR: 3.0) and computed tomographic angiography (CTA) revealed 13 variants
      (IQR: 3.5). Magnetic resonance cholangiopancreatography (MRCP) identified 4
      biliary variants (IQR: 1.3) and CT cholangiography identified 17 (IQR: 3.5). MRI
      and CT each showed 4 hepatic and portal venous variants (IQR MR: 3.4, CT: 2.8).
      CT and MR findings correlated well with intraoperative findings. In conclusion,
      both techniques proved to be efficient to evaluate potential living liver donors'
      anatomy in a single diagnostic step. The main advantage of CT lies in the ability
      to accurately assess the biliary anatomy.

PMID- 15973712
TI  - Nuclear beta-catenin promotes non-neural ectoderm and posterior cell fates in
      amphioxus embryos.
AB  - In vertebrate development, Wnt/beta-catenin signaling has an early role in
      specification of dorsal/anterior identity and a late one in posterior
      specification. To understand the evolution of these roles, we cloned beta-catenin
      from the invertebrate chordate amphioxus. The exon/intron organization of beta
      catenin is highly conserved between amphioxus and other animals including a
      cnidarian, but not Drosophila. In development, amphioxus beta-catenin is
      concentrated in all nuclei from the 16-cell stage until the onset of gastrulation
      when it becomes undetectable in presumptive mesendoderm. Li(+), which up
      regulates Wnt/beta-catenin signaling, had no detectable effect on axial
      patterning when applied before the late blastula stage, suggesting that a role
      for beta-catenin in specification of dorsal/anterior identity may be a vertebrate
      innovation. From the mid-gastrula through the neurula stage, the highest levels
      of nuclear beta-catenin are around the blastopore. In the early neurula, beta
      catenin is down-regulated in the neural plate, but remains high in adjacent non
      neural ectoderm. Embryos treated with Li(+) at the late blastula stage are
      markedly posteriorized and lack a neural plate. These results suggest that in
      amphioxus, as in vertebrates, down-regulation of Wnt/beta-catenin signaling in
      the neural plate is necessary for maintenance of the neuroectoderm and that a
      major evolutionarily conserved role of Wnt/beta-catenin signaling is to specify
      posterior identity and pattern the anterior/posterior axis.

PMID- 15973713
TI  - Liver transplantation for HCV-related cirrhosis in a patient with gastric mucosa
      associated lymphoma (MALToma) pretreated with rituximab.
AB  - End-stage liver disease due to chronic hepatitis C virus (HCV) infection is now
      the most frequent indication for liver transplantation. HCV infection is
      associated with extrahepatic disease including cryoglobulinemia and lymphoma. The
      number of patients requiring liver transplantation (LT) for cirrhosis secondary
      to HCV infection has increased over the past 10 years; consequently, associated
      extrahepatic manifestations (in particular hematological malignancies) will be
      more commonly observed in this patient group. The management of patients with
      both end-stage liver disease and significant HCV-related extrahepatic disease is
      undefined. We report a 59-year-old man in whom extranodal marginal-zone B-cell
      lymphoma arising in gastric mucosa-associated lymphoid tissue (MALToma) was
      successfully eradicated by rituximab administration and gastrectomy at LT for HCV
      related cirrhosis. Our experience with rituximab in this patient suggests that it
      can be used safely in the setting of severe liver disease due to HCV infection.
      Rituximab may be useful in preventing progression of NHL until surgical
      extirpation is possible.

PMID- 15973714
TI  - The molecular adsorbent recycling system (MARS) and transmembrane transport of
      albumin-bound toxins.

PMID- 15973716
TI  - Mycophenolate mofetil combination therapy improves long-term outcomes after liver
      transplantation in patients with and without hepatitis C.
AB  - To evaluate the impact of mycophenolate mofetil (MMF) on long-term outcomes of
      tacrolimus and corticosteroids, we analyzed data reported to the Scientific
      Registry of Transplant Recipients for 11,670 adult patients (3463 with hepatitis
      C [HCV]) who underwent primary, single-organ, liver transplantation between 1995
      and 2001. Patients who were discharged from the hospital on tacrolimus-based
      immunosuppression with (n = 4466; n = 1323 HCV) or without MMF (n = 7204; n =
      2140 HCV) were included in the analysis. Recipients treated at discharge with
      MMF, tacrolimus, and corticosteroids had significantly increased patient survival
      (81.0% vs. 77.0% at 4 years, P < 0.0001) and graft survival (76.4% vs. 72.9%, P <
      0.0001), and lower rates of acute rejection (29.0% vs. 33.4%, P < 0.001) as
      compared to recipients treated at discharge with tacrolimus and corticosteroids
      alone. A trend toward lower rates of death from infection was observed (6.1% at 4
      years for MMF vs. 7.1% at 4 years for tacrolimus and corticosteroids, P =
      0.0508), but this result did not reach statistical significance. In multiple
      regression analyses, MMF triple therapy at discharge was associated with a
      reduced risk of death (hazard ratio [HR] = 0.77, P < 0.001), graft loss (HR =
      0.81, P < 0.001), acute rejection (HR = 0.89, P = 0.002), and death from
      infectious complications (HR = 0.80, P = 0.007). Outcomes were similar for the
      cohort with HCV.In conclusion, the addition of MMF at discharge to tacrolimus
      based immunosuppression is associated with improved long-term outcomes after
      liver transplantation in patients with and without HCV.

PMID- 15973718
TI  - Management of the hepatitis B virus in the liver transplantation setting: a
      European and an American perspective.

PMID- 15973719
TI  - Changes in oxyhemoglobin dissociation curve in intrabdominal organs during pig
      experimental orthotopic liver transplantation.
AB  - Liver transplantation has become a gold standard treatment for irreversible liver
      disease. Conventional measures of oxygenation are inadequate to understand the
      dynamics of regional oxygen metabolism during liver transplantation because they
      represent global markers of tissue dysoxia. Therefore, the addition of an
      assessment of the hemoglobin O(2) binding capacity can give a better insight into
      systemic and regional tissue oxygenation and can reflect a more accurate
      estimation of oxygen release to the tissues than can the hemoglobin, the PaO(2)
      and SaO(2) alone. This prospective study was designed to evaluate possible
      alterations in the oxyhemoglobin dissociation curve of vital end organs (small
      bowel, liver, and kidney) in an experimental liver transplantation model. Fifteen
      pigs with body weights ranging from 25 to 30 kg were used for the study. Five
      healthy pigs underwent a sham operation under general anesthesia (group A
      control). Ten pigs underwent orthotopic liver transplantation (OLT). Five of them
      were healthy (group B), whereas the other five were in acute liver failure, which
      had been surgically induced (group C). Systemic arterial blood pressure, cardiac
      index, and pulmonary and systemic vascular resistance indexes were measured.
      Venous blood gas analysis was also performed from pulmonary artery, superior
      mesenteric, hepatic, and renal veins at well-defined timepoints during the course
      of the OLT. A statistically significant (P < 0.05) decrease of P(50) in groups B
      and C compared with group A was observed 30 minutes after reperfusion in the
      systemic circulation, hepatic, and renal veins. This coincided with a decrease in
      animal temperature 30 minutes after reperfusion. Regarding group C, after
      reperfusion of the newly transplanted liver there was a significant increase of
      P(50) in the small bowel in comparison to baseline values. In conclusion, these
      changes in P(50) may suggest the occurrence of abnormal tissue oxygenation after
      reperfusion.

PMID- 15973720
TI  - Critical analysis of the pediatric end-stage liver disease scoring system: a
      single center experience.
AB  - The Pediatric End-Stage Liver Disease (PELD) scoring system is a new nationally
      utilized formula developed to provide a continuous numerical assessment of the
      risk of death in order to allocate livers to children for transplantation. A
      retrospective review of the clinical course of children undergoing liver
      transplantation at the Mount Sinai Medical Center was performed in order to
      assess the effectiveness of this scoring system in the first 24 months of its
      utilization. Forty-eight patients underwent liver transplantation with overall
      patient and graft survival rates of 98% and 96%, respectively. In 23 cases the
      PELD scoring system determined waiting time for transplantation. Of these 23
      patients, 7 moved to the intensive care unit (ICU). Only 2 of 23 patients
      underwent transplantation with their actual PELD score. The rest required
      petition for exception (17) or status 1 listing (4). Significant morbidity
      occurred while awaiting transplantation: failure to thrive (78%), ascites (73%),
      hemorrhage (49%), infectious complications (39%), encephalopathy (30%),
      peritonitis (17%), pathologic bone fractures (13%), and hepatopulmonary syndrome
      (9%). In patients with PELD scores granted by exception the average score that
      did not yield a liver offer was 38 with an average waiting time of 55 days. At
      the time of transplantation actual PELD score averaged 22, while the petitioned
      score was 40. Based upon our center's initial experience, the current PELD
      scoring system is not adequate. Actual PELD scores did not lead to timely
      allocation of livers to children. It appears that this scoring system
      underestimates the near-term risk of death. Urgent reassessment is required to
      prevent potential morbidity and mortality in children. In conclusion the United
      Network for Organ Sharing policy that permits granting of exceptions has
      circumvented these problems with the PELD scoring system.

PMID- 15973721
TI  - Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD
      mutant using add-on adefovir dipivoxil plus lamivudine.
AB  - Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection
      may improve clinical state and suppress viral replication before liver
      transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We
      report the results of liver transplantation in 16 patients with
      pretransplantation YMDD mutants after receiving lamivudine treatment for a median
      of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on
      to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at
      (n = 5) liver transplantation, and the combination was continued indefinitely
      thereafter. Eight patients received additional intravenous hepatitis B immune
      globulin (HBIG) for a median of 24 months. Fifteen patients with known pre
      adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3)
      to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1
      patient remained positive for HBV DNA (by quantitative polymerase chain reaction
      [qPCR]) at the time of liver transplantation, and the titer was greater than10(5)
      copies/mL in 8 patients. The median follow-up after liver transplantation was
      21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2
      months after transplantation, and 15 patients (94%) were alive with the original
      graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the
      latest follow-up. Fourteen patients had cleared hepatitis B surface antigen
      (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine
      without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA,
      however, was negative, and there was no biochemical or histological evidence of
      recurrence. Adefovir dipivoxil was well tolerated with no significant renal
      toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus
      lamivudine therapy provides effective prophylaxis in patients with
      pretransplantation YMDD mutant that may be actively replicating. The cost
      effectiveness of additional passive immunoprophylaxis remains to be defined.

PMID- 15973722
TI  - Pharmacogenetic association with adverse drug reactions to azathioprine
      immunosuppressive therapy following liver transplantation.
AB  - Azathioprine (AZA) is a thiopurine prodrug commonly used in triple
      immunosuppressive therapy following liver transplantation. Approximately 1 in 10
      patients suffers side effects in response to the drug, the most problematic being
      bone marrow toxicity. There is evidence that polymorphisms in the genes encoding
      thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase
      (ITPase) predict adverse drug reactions to AZA therapy. Furthermore, common
      genetic polymorphisms in the gene encoding methylenetetrahydrofolate reductase
      (MTHFR) may have an indirect impact on thiopurine drug methylation by influencing
      levels of the methyl donor S-adenosylmethionine (SAM). The aim of this study was
      to determine whether polymorphisms in these candidate pharmacogenetic loci
      predict adverse drug reactions to AZA immunosuppressive therapy in liver
      transplant patients. A series of 65 liver transplant recipients were recruited to
      the study from the Liver Transplant Out-Patient clinic at The Royal Infirmary of
      Edinburgh. Clinical response to AZA was retrospectively correlated against TPMT
      activity, TPMT*2, *3A, and *3A genotypes, inosine triphosphatase (ITPA) 94C>A and
      IVS2+21A>C genotypes, and MTHFR 677C>T and 1298A>C genotypes. Variant TPMT, ITPA,
      and MTHFR genotypes were not significantly associated with adverse drug reactions
      to AZA, including bone marrow suppression. However, the 2 patients who suffered
      nodular regenerative hyperplasia (NRH) were both heterozygous for the TPMT*3A
      mutation. In conclusion, our findings suggest that TPMT, ITPA, and MTHFR
      genotypes do not predict adverse drug reactions, including bone marrow
      suppression, in liver transplant patients. However, the possible association
      between NRH and a heterozygous TPMT genotype should be investigated further.

PMID- 15973723
TI  - Liver transplantation for cardiac failure in patients with hereditary hemorrhagic
      telangiectasia.
AB  - Liver involvement in hereditary hemorrhagic telangiectasia may lead to high
      output cardiac failure. Few data have been reported on orthotopic liver
      transplantation (OLT) for these patients. In this paper, we describe two patients
      treated by OLT as a salvage procedure for cardiac failure, and we review
      literature on this subject. Our two patients resumed normal cardiac function
      after OLT. This procedure appears to be a promising therapy with good long-term
      results despite dissection difficulties encountered due to the collateral
      arterial network reorganization.

PMID- 15973724
TI  - Hepatitis C virus-specific CD8+ T cells restricted by donor HLA alleles following
      liver transplantation.
AB  - By necessity, human liver transplantation is performed across HLA barriers. As a
      result, intracellular infection of the allograft presents a unique immunologic
      challenge for the recipient's immune system. In this study, we describe the
      presence of HLA-A2-restricted, hepatitis C virus (HCV)-specific CD8+ T cells in
      liver transplant recipients in whom the allograft is HLA-A2 positive and the
      recipient is HLA-A2 negative. These memory-effector T cells are recipient derived
      and recognize HCV peptide uniquely in the context of HLA-A2. Furthermore, these
      cells were absent before the transplant, suggesting that the allograft is capable
      of selectively expanding naive CD8+ T cells. The in vitro specificity to donor
      HLA allele-restricted CD8+ T cells suggests that these cells may function to
      control HCV spread in the allograft.

PMID- 15973725
TI  - Liver transplantation after backtable resection of giant hemangioma.

PMID- 15973726
TI  - Systematic review and validation of prognostic models in liver transplantation.
AB  - A model that can accurately predict post-liver transplant mortality would be
      useful for clinical decision making, would help to provide patients with
      prognostic information, and would facilitate fair comparisons of surgical
      performance between transplant units. A systematic review of the literature was
      carried out to assess the quality of the studies that developed and validated
      prognostic models for mortality after liver transplantation and to validate
      existing models in a large data set of patients transplanted in the United
      Kingdom (UK) and Ireland between March 1994 and September 2003. Five prognostic
      model papers were identified. The quality of the development and validation of
      all prognostic models was suboptimal according to an explicit assessment tool of
      the internal, external, and statistical validity, model evaluation, and
      practicality. The discriminatory ability of the identified models in the UK and
      Ireland data set was poor (area under the receiver operating characteristic curve
      always smaller than 0.7 for adult populations). Due to the poor quality of the
      reporting, the methodology used for the development of the model could not always
      be determined. In conclusion, these findings demonstrate that currently available
      prognostic models of mortality after liver transplantation can have only a
      limited role in clinical practice, audit, and research.

PMID- 15973727
TI  - Nanomechanical properties of self-reinforced composite poly(methyl methacrylate)
      as a function of processing temperature.
AB  - Understanding the wear characteristics of bone cement and its alternatives is
      critical to improving the quality and longevity of hip replacements. A novel
      composite material, self-reinforced composite poly(methyl methacrylate), has been
      previously developed for potential use as a pre-coat material for hip implants.
      The goal of this work was to examine the properties of self-reinforced composite
      poly(methyl methacrylate) as a function of processing temperature.
      Nanoindentation tests were performed to measure hardness and modulus of self
      reinforced composite poly(methyl methacrylate) at the nanoscale. Nanoscratch
      tests were performed parallel, orthogonal, and longitudinal to composite fibers
      to measure residual scratch depths. Significant differences were found in the
      hardness, modulus, and residual scratch depth as a function of processing
      temperature when compared to poly(methyl methacrylate). As processing temperature
      is increased, hardness decreased and residual scratch depths increased. Data also
      showed that fiber orientation plays a critical role in scratch resistance.
      Scratching orthogonal to fiber orientation produced the least residual scratch
      depth ranging from 524 nm at 105 degrees C to 838 nm at 150 degrees C, compared
      to a residual scratch depth for poly(methyl methacrylate) of 842 nm.

PMID- 15973728
TI  - Heparin structures in FGF-2-dependent morphological transformation of astrocytes.
AB  - Fibroblast growth factor-2 (FGF-2) participates in the morphological
      transformation of astrocytes (stellation) during the formation of glial scars in
      injured brains. In the current study, we used quantitative morphometric analysis
      to investigate the structural requirements for heparin's enhancement of FGF-2
      induced stellation of cultured cortical astrocytes. Native heparin significantly
      promoted FGF-2-dependent astrocytic stellation, whereas heparin hexasaccharide
      inhibited FGF-2-dependent stellation. Furthermore, 2-O-, 6-O-, and N-desulfated
      heparins were unable to promote FGF-2-dependent stellation. The stellation
      induced by FGF-2 or by a combination of FGF-2 and native heparin was inhibited by
      SU5402, an FGF receptor inhibitor. These results demonstrate that the length and
      sulfated position of heparin are important for its enhancement of FGF-2-dependent
      astrocyte stellation. In addition, our findings show that heparin
      oligosaccharides are useful for regulating the FGF-2-dependent astrocytic
      transformation.

PMID- 15973729
TI  - Combined chondrocyte-copolymer implantation with slow release of basic fibroblast
      growth factor for tissue engineering an auricular cartilage construct.
AB  - Basic fibroblast growth factor (b-FGF) may have a role in tissue-engineered
      chondrogenesis. However, when applied in solution, b-FGF rapidly diffuses from
      the implant site. In another approach for tissue engineering, poly-lactide-based
      copolymers have shown promise as scaffolds for chondrocytes used to tissue
      engineer auricular cartilage in the shape of an ear. This study evaluated the
      effectiveness of b-FGF impregnated in gelatin microspheres to achieve slow growth
      factor release for augmenting the in vivo chondrogenic response. Whereas 125I
      labeled b-FGF injected in solution showed rapid in vivo clearance from the
      injection site (only 3% residual after 24 h), when incorporated into gelatin
      microspheres, 44% and 18% of the b-FGF remained at 3 and 14 days, respectively.
      Canine chondrocytes were isolated and grown in vitro onto ear-shaped poly
      lactide/caprolactone copolymers for 1 week, then implanted into the dorsal
      subcutaneous tissue of nude mice; implants contained b-FGF either in free
      solution or in gelatin microspheres. A third group underwent preinjection of b
      FGF in gelatin microspheres 4 days before chondrocyte-copolymer implantation. The
      implants with b-FGF-incorporated microspheres showed the greatest chondrogenic
      characteristics at 5 and 10 weeks postoperatively: good shape and biomechanical
      trait retention, strong (histologic) metachromasia, rich vascularization of
      surrounding tissues, and increased gene expression for type II collagen
      (cartilage marker) and factor VIII-related antigen (vascular marker). In the case
      of implant site preadministration with b-FGF-impregnated microspheres, the
      implant architecture was not maintained as well, and reduced vascularization and
      metachromasia was also apparent. In conclusion, these findings indicate that a
      sustained release of b-FGF augments neovascularization and chondrogenesis in a
      tissue-engineered cartilage construct.

PMID- 15973730
TI  - Simple and accurate fracture toughness testing methods for pyrolytic
      carbon/graphite composites used in heart-valve prostheses.
AB  - The fracture toughness is a critical material property for the pyrolytic carbon
      materials used in mechanical heart-valve prostheses; however, making accurate
      toughness measurements has traditionally been problematic due to difficulties in
      fatigue precracking specimens. In this work, a simple, effective, and reliable
      precracking method is presented where a sharp precrack is "popped in" from a
      razor micronotch, which allows significant savings of time and materials relative
      to fatigue precracking methods. It is further shown that equivalent results may
      be obtained using razor micronotched specimens directly without precracking,
      provided the notch is sufficiently sharp. Indeed, mean toughness values of 1.46+/
      0.13 and 1.35+/-0.09 MPa radicalm were obtained for the pyrolytic carbon-coated
      graphite materials, using precracked and razor micronotched specimens,
      respectively. The difference between these mean values proved to be statistically
      insignificant, and these values are in general agreement with published fracture
      toughness results obtained using fatigue precracked specimens.

PMID- 15973731
TI  - Platelet-derived growth factors in the developing avian heart and maturating
      coronary vasculature.
AB  - Platelet-derived growth factors (PDGFs) are important in embryonic development.
      To elucidate their role in avian heart and coronary development, we investigated
      protein expression patterns of PDGF-A, PDGF-B, and the receptors PDGFR-alpha and
      PDGFR-beta using immunohistochemistry on sections of pro-epicardial quail-chicken
      chimeras of Hamburger and Hamilton (HH) 28-HH35. PDGF-A and PDGFR-alpha were
      expressed in the atrial septum, sinus venosus, and throughout the myocardium,
      with PDGFR-alpha retreating to the trabeculae at later stages. Additionally, PDGF
      A and PDGFR-alpha were present in outflow tract cushion mesenchyme and
      myocardium, respectively. Small cardiac nerves and (sub)epicardial cells
      expressed PDGF-B and PDGFR-beta. Furthermore, endothelial cells expressed PDGF-B,
      while vascular smooth muscle cells and interstitial epicardium-derived cells
      expressed PDGFR-beta, indicating a role in coronary maturation. PDGF-B is also
      present in ventricular septal development, in the absence of any PDGFR.
      Epicardium-derived cells in the atrioventricular cushions expressed PDGFR-beta.
      We conclude that all four proteins are involved in myocardial development,
      whereas PDGF-B and PDGFR-beta are specifically important in coronary maturation.

PMID- 15973732
TI  - Fatal subclavian stent infection remote from implantation.
AB  - We report the unusual case of a 66-year-old alcoholic male who presented with
      acute arm ischemia 4 months following ipsilateral subclavian artery stenting. The
      patient had a petechial rash and Janeway lesions in the distribution of the
      affected subclavian artery. He had been treated for an infected dialysis graft 10
      days prior to entry into the hospital. Subsequent angiogram confirmed a patent
      stent with intraluminal filling defects and occlusion of the brachial artery.
      Thrombectomy yielded material that was consistent with septic emboli and CT scan
      of the chest was suggestive of a mycotic aneurysm around the stent. The
      subclavian stent was removed surgically and the aneurysm was repaired.
      Unfortunately, the patient had multiple comorbidities and died of complications
      during recovery. This is the first case of a subclavian stent infection following
      septicemia remote from implantation.

PMID- 15973733
TI  - Ontogeny of tyrosine hydroxylase mRNA expression in mid- and forebrain:
      neuromeric pattern and novel positive regions.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of
      catecholamines and, thus, critical in determining the catecholaminergic
      phenotype. In this study, we have examined the expression of TH mRNA by in situ
      hybridization in the embryonic mouse forebrain and midbrain and have mapped its
      localization according to the neuromeric pattern. We find that early in embryonic
      development, 10 to 12 days post coitum (dpc), TH mRNA is expressed in ample
      continuous regions of the neuroepithelium, extending across several neuromeres.
      However, from 12.5 dpc onward, the expression becomes restricted to discrete
      regions, which correspond to the dopaminergic nuclei (A8 to A15). In addition to
      these nuclei previously described, TH mRNA is also observed in regions that do
      not express this enzyme according to immunohistochemical studies. This difference
      in relation to protein expression pattern is consequent with the known
      posttranscriptional regulation of TH expression. The most representative example
      of a novel positive region is the conspicuous mRNA expression in both medial and
      lateral ganglionic eminences. This result agrees with reports describing the
      capacity of striatal stem cells (that is, located at the lateral ganglionic
      eminence) to become dopaminergic in vitro. Other regions include the isthmic
      mantle layer and the early floor plate of the midbrain-caudal forebrain. On the
      whole, the expression map we have obtained opens new perspectives for
      evolutionary/comparative studies, as well as for therapeutic approaches looking
      for potentially dopaminergic cells. Developmental Dynamics 234:709-717, 2005. (c)
      2005 Wiley-Liss, Inc.

PMID- 15973734
TI  - Intercellular growth factor signaling and the development of mouse tracheal
      submucosal glands.
AB  - To provide a genetic framework for investigating changes in airway submucosal
      gland function in human respiratory disease, we have investigated their
      counterparts in normal and mutant mice. We describe their morphogenesis in
      relation to the expression of genes encoding conserved intercellular signaling
      pathways. Submucosal glands are severely reduced in number and size in mice
      heterozygous for Fgf10. Glands are completely absent in mice lacking
      Ectodysplasin (Eda) and Edaradd (Eda receptor adaptor protein), members of the
      tumor necrosis (TNF) superfamily of signaling factors. Furthermore, components of
      the Eda and closely related pathways are transcribed throughout the respiratory
      system in the adult mouse. Finally, the temporal and spatial pattern of Bmp4
      expression suggests that it may control submucosal gland development and
      homeostasis. Taken together, our observations have important implications for the
      better understanding of the submucosal gland remodeling that occurs in human
      respiratory disease.

PMID- 15973735
TI  - Cells of all somitic compartments are determined with respect to segmental
      identity.
AB  - Development of somite cells is orchestrated by two regulatory processes.
      Differentiation of cells from the various somitic compartments into different
      anlagen and tissues is regulated by extrinsic signals from neighboring structures
      such as the notochord, neural tube, and surface ectoderm. Morphogenesis of these
      anlagen to form specific structures according to the segmental identity of each
      somite is specified by segment-specific positional information, based on the Hox
      code. It has been shown that following experimental rotation of presomitic
      mesoderm or newly formed somites, paraxial mesodermal cells adapt to the altered
      signaling environment and differentiate according to their new orientation. In
      contrast, presomitic mesoderm or newly formed somites transplanted to different
      segmental levels keep their primordial segmental identity and form ectopic
      structures according to their original position. To determine whether all cells
      of a segment, including the dorsal and ventral compartment, share the same
      segmental identity, presomitic mesoderm or newly formed somites were rotated and
      transplanted from thoracic to cervical level. These experiments show that cells
      from all compartments of a segment are able to interpret extrinsic local signals
      correctly, but form structures according to their original positional information
      and maintain their original Hox expression in the new environment.

PMID- 15973736
TI  - An automated in situ hybridization screen in the Medaka to identify unknown
      neural genes.
AB  - Despite the fact that a large body of factors that play important roles in
      development are known, there are still large gaps in understanding the genetic
      pathways that govern these processes. To find previously unknown genes that are
      expressed during embryonic development, we optimized and performed an automated
      whole-mount in situ hybridization screen on medaka embryos at the end of
      somitogenesis. Partial cDNA sequences were compared against public databases and
      identified according to similarities found to other genes and gene products.
      Among 321 isolated genes showing specific expression in the central nervous
      system in at least one of five stages of development, 55.14% represented genes
      whose functions are already documented (in fish or other model organisms).
      Additionally, 16.51% were identified as conserved unknown genes or genes with
      unknown function. We provide new data on eight of these genes that presented a
      restricted expression pattern that allowed for formulating testable hypotheses on
      their developmental roles, and that were homologous to mammalian molecules of
      unknown function. Thus, gene expression screening in medaka is an efficient tool
      for isolating new regulators of embryonic development, and can complement genome
      sequencing projects that are producing a high number of genes without ascribed
      functions.

PMID- 15973737
TI  - Epidemiology and outcomes of serious influenza-related infections in the cancer
      population.
AB  - BACKGROUND: Although patients with cancer generally respond favorably to
      vaccination, they may not receive annual influenza vaccinations. The current
      population-based study described the epidemiology and outcomes of potentially
      preventable, serious influenza-related infections in patients with cancer.
      METHODS: From the Nationwide Inpatient Sample, the authors created a subsample
      that included discharges with any International Classification of Diseases, ninth
      revision, diagnosis code for cancer and principal diagnosis code for influenza,
      bronchopneumonia, or pneumonia caused by an unspecified organism. From the latter
      two diagnosis codes, the authors estimated excess cases during the influenza
      season for each year and stratum, then selected a random sample from fall and
      winter discharges. Subset analyses included weighted sample means, frequencies,
      and analysis of variance values. The authors converted charges to costs using
      cost-to-charge ratios and inflated these to 2003 U.S. dollars. Hospitalization
      and mortality rates were calculated using 5-year cancer prevalence estimates.
      RESULTS: The estimated mean annual hospital discharges of patients with cancer
      with potentially preventable, serious influenza-related infections numbered
      16,000. The average length and cost per stay were 6 days and > USD 6300,
      respectively. Approximately 9% of patients died in the hospital and 31% needed
      further skilled care. The estimated age-specific rates for hospitalization and
      death per 100,000 in the prevalent cancer population were 219 and 17.4,
      respectively, for patients age < 65 years and 623 and 59.4, respectively, for
      those age > or = 65 years. Hospitalization costs averaged USD 1300 more for
      patients age < 65 years. CONCLUSIONS: Death from influenza-related infections
      occurred in an estimated 9% of patients with cancer hospitalized for such. Using
      recommended vaccination schedules for patients with cancer and their contacts
      reduced hospitalizations, treatment delays, and deaths in this highly susceptible
      population.

PMID- 15973738
TI  - Comparative analysis of Six 3 and Six 6 distribution in the developing and adult
      mouse brain.
AB  - Six 3 and Six 6 genes are two closely related members of the Six/sine oculis
      family of homeobox containing transcription factors. Their expression and
      function at early stages of embryonic development has been widely addressed in a
      variety of species. However, their mRNA distribution during late embryonic,
      postnatal, and adult brain barely has been analyzed. Here, we show that despite
      their initial overlap in the anterior neural plate, the expression of Six 3 and
      Six 6 progressively segregates to different regions during mammalian brain
      development, maintaining only few areas of partial overlap in the thalamic and
      hypothalamic regions. Six 3, but not Six 6, is additionally expressed in the
      olfactory bulb, cerebral cortex, hippocampus, midbrain, and cerebellum. These
      distinct patterns support the idea that Six 3 and Six 6 are differentially
      required during forebrain development.

PMID- 15973741
TI  - Selective guest encapsulation by a cobalt-assembled cage molecule.
AB  - Metal-assembled resorcinarene-based cages enclose space and entrap organic
      molecules from water. Addition of cobalt(II) ions to a neutral, aqueous solution
      of a resorcinarene that has iminodiacetic acids attached to its upper rim results
      in the formation of cages. These cages not only entrap organic molecules, but
      they do so in a selective manner. Guests with optimum size, shape, and polarity
      are preferentially entrapped. For example, selection of p-xylene is twenty
      thousand times more favorable than that of m-xylene. The enthalpy of
      resorcinarene deprotonation and cage formation was calculated by performing
      calorimetry studies and ranged from -305 to -348 kJ mol(-1). The change in
      enthalpy of guest encapsulation varied by as much as 43 kJ mol(-1). The
      differences in change in free energy of guest encapsulation varied by -16 kJ mol(
      1). The changes in enthalpy and free energy of guest encapsulation were used to
      calculate the changes in entropy, which ranged from -97 to +37 J mol(-1) K(-1).
      An enthalpy-entropy compensation of guest encapsulation was observed.

PMID- 15973739
TI  - Developmental changes in heteromeric P2X(2/3) receptor expression in rat
      sympathetic ganglion neurons.
AB  - We have used whole cell patch clamp recording and immunohistochemistry to
      investigate the expression of P2X(2/3) receptors in rat superior cervical
      ganglion neurons during late embryonic and early post-natal development. Neurons
      from E18 and P1 animals responded to the nicotinic agonist
      dimethylphenylpiperazinium (DMPP), and the purinoceptor agonists ATP and
      alpha,beta-meATP with sustained inward currents. Responsiveness to DMPP was
      maintained at P 17, while that to ATP declined dramatically, and responses to
      alpha,beta-meATP were rarely detected. Immunohistochemistry for the P2X(3)
      subunit revealed widespread staining in superior cervical ganglia from P1 rats,
      but little immunoreactivity in ganglia from P17 animals. In neurons from P1
      animals, the response to alpha,beta-meATP exhibited pharmacological properties of
      the heteromeric P2X(2/3) receptor. In conclusion, sympathetic neurons of the rat
      superior cervical ganglion are more responsive to ATP and alpha,beta-meATP at
      birth and during the early post-natal period, due largely to the expression of
      the P2X(3) subunit, but these responses are much reduced in mature rats.

PMID- 15973740
TI  - Histologic coagulative tumor necrosis as a prognostic indicator of renal cell
      carcinoma aggressiveness.
AB  - BACKGROUND: Prognostic markers for renal cell carcinoma (RCC), such as patient
      symptoms, tumor stage, tumor size, and tumor grade, are useful for determining
      appropriate follow-up and selecting patients for adjuvant therapy. Histologic
      coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has
      not previously been extensively described or investigated. Hence, the objective
      of the current study was to characterize tumor necrosis as a prognostic feature
      of RCC. METHODS: The authors of the current study identified 3009 patients
      treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy
      Registry (Rochester, MN). Associations of tumor necrosis with clinical,
      laboratory, and pathologic features were examined with chi-square, Fisher exact
      test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with
      the Kaplan-Meier method, and associations with outcome were assessed with Cox
      proportional hazard models. RESULTS: Tumor necrosis was present in 690 of 2445
      (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe
      RCCs. The risk ratio for death from RCC in patients with necrotic compared with
      non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001)
      for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI:
      0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell
      RCC persisted even after multivariate adjustment for tumor stage, size, and grade
      (risk ratio 1.90; P < 0.001). CONCLUSIONS: Histologic coagulative tumor necrosis
      is an independent predictor of outcome for clear cell and chromophobe RCC, and it
      should be routinely reported and used in clinical assessment.

PMID- 15973742
TI  - Synthesis and properties of electrophosphorescent chelating polymers with iridium
      complexes in the conjugated backbone.
AB  - The synthesis of electrophosphorescent chelating polymers by Suzuki
      polycondensation of A-A- and B-B-type monomers is described, in which the
      fluorene-alt-carbazole (PFCz) segment is used as polymer backbone. By using alkyl
      substituted ligands of iridium complex monomers, chelating copolymers with higher
      contents of iridium complex can be synthesized. Chemical and photophysical
      characterization confirm that the Ir complex is incorporated into the polymer
      backbone as one of the monomer repeat units by means of two 5-bromotolylpyridine
      ligands. Chelating polymers with Ir complexes in the conjugated polymer backbone
      show highly efficient energy transfer of excitons from the PFCz host segment to
      the Ir complex by an intramolecular trapping mechanism. The external quantum and
      luminous efficiencies of a device made with PFCzMppyIrhm4 copolymer reach 4.1 %
      ph/el (photons/electron) and 5.4 cd A(-1), respectively, at a current density of
      32.2 mA cm(-2), an emission peak of 577 nm, and a luminance of 1730 cd cm(-2).
      Most important, the devices made from the chelating copolymers show no notable
      efficiency decay with increasing current density due to reduced concentration
      quenching and triplet-triplet (T-T) annihilation. This indicates that
      incorporation of the phosphorescent complex into the rigid conjugated polymer
      main chain is a new way to simultaneously realize high efficiency, long-term
      stability, and simple processing of phosphorescent polymer light-emitting diodes.

PMID- 15973743
TI  - Nonlinear optical properties in calix[n]arenes: orientation effects of monomers.
AB  - We investigate the nonlinear optical (NLO) polarizations for various geometric
      arrangements of the dipolar chromophores in a calix[n]arene geometry. The
      interactions were studied by using (HF)3 as model compounds both in parallel and
      frustrated orientations. The interdipolar angle between the monomer molecules is
      varied so that many different arrangements of the dipoles can be realized which
      is associated with the opening up of the calix[n]arene rings. Quantum-chemical
      calculations at both ab initio and semiempirical levels, show that the all
      parallel arrangement of the dipoles exhibit the maximum magnitude for the
      nonlinear optical coefficients at small interdipolar angles for all interdipolar
      distances. In the frustrated orientations however, the NLO response is maximum at
      large interdipolar angles corresponding to the flattened calix[n]arene rings. The
      role of hydrogen bonding in stabilizing these assemblies in various conformations
      has been investigated. Crystallographic database analysis for calix[3]arenes
      shows that optical properties in real molecular systems can be modeled based on
      our simple interaction theory.

PMID- 15973744
TI  - IPy2BF4-mediated rearrangements of 1,2-difunctionalized compounds and olefins.
AB  - Acetal derivatives are easily obtained from 1,2-difunctionalized compounds by a
      new reaction mediated by IPy2BF4 with a mechanism based on a 1,2-migration of
      aryl or alkyl groups. A new oxidative rearrangement reaction of olefins is also
      described. Moreover, when this metal-free protocol is applied to cyclic olefins,
      interesting ring-contraction reactions are observed. The new methodologies
      described here are a clean and efficient alternative to known strategies that
      make use of potentially toxic metallic complexes.

PMID- 15973745
TI  - Intramolecular hydrogen-bond-assisted planarization of asymmetrically
      functionalized alternating phenylene-pyridinylene copolymers.
AB  - We report on the synthesis and characterization of a series of asymmetrically
      functionalized amphiphilic polymers with alternating pi-donor units (e.g.,
      substituted benzene) and pi-acceptor units (e.g., pyridine) along the polymer
      backbone. The purpose of our present work involves incorporation of functional
      groups along the main chain to form intrachain hydrogen bonds, which promote
      planarization of the polymer backbone, and to fine-tune the optical properties.
      The structure-property relationship of polymers P1-P6 was investigated by means
      of analytical methods, such as FTIR spectroscopy, 1H and 13C NMR spectroscopy,
      UV/Vis spectroscopy, fluorescence spectroscopy, gel permeation chromatography,
      thermogravimetric analysis, cyclic voltammetry, and X-ray powder diffraction. All
      polymers were soluble in common organic solvents, and the optical and
      fluorescence spectra of the polymers showed significant changes according to the
      formation (P4, P5) or absence (P6) of intramolecular hydrogen bonding along the
      polymer backbone. Moreover, the 2,6- or 3,5-linkage of the pyridine rings in P5
      and P6, respectively, reduced the conjugation along the polymer backbone and this
      is reflected in their optical properties. The optical properties of the polymers
      were influenced by the addition of acid (P1-P6), base (P4-P6), and metal ions
      (e.g., Cu2+, Fe3+, Ag+, Ni2+, Pd2+, Mn2+, Zn2+, Mg2+, and Pr3+). Such polymers
      could be used in various applications, including sensors and stimuli-responsive
      displays.

PMID- 15973746
TI  - Synthesis, crystal structures, and properties of oxovanadium(IV)-lanthanide(III)
      heteronuclear complexes.
AB  - A new series of oxovanadium(IV)-lanthanide(III) heteronuclear complexes
      [Yb(H2O)8]2[(VO)2(TTHA)](3)21 H2O (1), {[Ho(H2O)7(VO)2(TTHA)][(VO)2(TTHA)](0.5)}
      8.5 H2O (2), {[Gd(H2O)7(VO)2(TTHA)][(VO)2(TTHA)](0.5)}8.5 H2O (3),
      {[Eu(H2O)7][(VO)2(TTHA)](1.5)} 10.5 H2O (4), and [Pr2(H2O)6(SO4)2][(VO)2(TTHA)]
      (5) (H6TTHA=triethylenetetraaminehexaacetic acid) were prepared by using the
      bulky flexible organic acid H(6)TTHA as structure-directing agent. X-ray
      crystallographic studies reveal that they contain the same [(VO)2(TTHA)]2- unit
      as building block, but the Ln3+ ion lies in different coordination environments.
      Although the lanthanide ions always exhibit similar chemical behavior, the
      structures of the complexes are not homologous. Compound 1 is composed of a
      [Yb(H2O)8]3+ ion and a [(VO)2(TTHA)]2- ion. Compounds 2 and 3 are isomorphous;
      both contain a trinuclear [Ln(H2O)7(VO)2(TTHA)]+ (Ln=Ho for 2 and Gd for 3) ion
      and a [(VO)2(TTHA)]2- ion. Compound 4 is an extended one-dimensional chain, in
      which each Eu3+ ion links two [(VO)2(TTHA)]2- ions. For 5, the structure is
      further assembled into a three-dimensional network with an interesting framework
      topology comprising V2Pr2 and V4Pr2 heterometallic lattices. Moreover, 4 and 5
      are the first oxovanadium(IV)-lanthanide(III) coordination polymers and thus
      enlarge the realm of 3d-4f complexes. The IR, UV/Vis, and EPR spectra and the
      magnetic properties of the heterometallic complexes were studied. Notably, 2
      shows unusual ferromagnetic interactions between the VO2+ and Ho3+ ions.

PMID- 15973747
TI  - Deformed phthalocyanines: synthesis and characterization of zinc phthalocyanines
      bearing phenyl substituents at the 1-, 4-, 8-, 11-, 15-, 18-, 22-, and/or 25
      positions.
AB  - The synthesis of a series of zinc phthalocyanines partially phenyl-substituted at
      the 1-, 4-, 8-, 11-, 15-, 18-, 22-, and/or 25-positions (the so-called alpha
      positions) is reported. Macrocycle formation based on 3,6-diphenylphthalonitrile,
      o-phthalonitrile, and zinc acetate predominantly yielded the near-planar
      disubstituted complex and opposite tetrasubstituted isomer, while the lithium
      method yielded the sterically hindered hexasubstituted complex and adjacent
      tetrasubstituted isomer. All compounds have been characterized by 1H NMR, MALDI
      TOF-MS, and elemental analysis methods. In addition, crystal structures have been
      solved for the di-, hexa-, and octasubstituted complexes and the adjacent
      tetrasubstituted isomer. DFT geometry optimization calculations predict more
      highly deformed structures than those observed in the crystals. The packing force
      of the crystals cannot therefore be ignored, particularly for the less phenyl
      substituted derivatives. The crystal structures have revealed that overlap of the
      phenyl groups causes substantial deformation of the phthalocyanine (Pc) ligands
      within the crystals, while strong pi-pi stacking in the remainder of the Pc
      moiety lacking phenyl substituents can suppress the impact of the deformation.
      Absorption spectra show sizable red shifts of the Q-band with increasing number
      of phenyl groups. Analysis of the results of absorption spectra and
      electrochemical measurements reveals that a substantial portion of the red shift
      is attributable to the ring deformations. Molecular orbital calculations lend
      further support to this conclusion. A moderately intense absorption band emerging
      at around 430 nm for highly deformed octaphenyl-substituted zinc Pc can be
      assigned to the HOMO-->LUMO+3 transition, which is parity-forbidden for planar
      Pcs, but becomes allowed since the ring deformations remove the center of
      symmetry.

PMID- 15973748
TI  - Efficient C-F and C-C activation by a novel N-heterocyclic carbene-nickel(0)
      complex.
AB  - The NHC-stabilized complex [Ni2(iPr2Im)4(cod)] (1) was isolated in good yield
      from the reaction of [Ni(cod)2] with 1,3-diisopropylimidazole-2-ylidene (iPr2Im).
      Compound 1 is a source of the [Ni(iPr2Im)2] complex fragment in stoichiometric
      and catalytic transformations. The reactions of 1 with ethylene and CO under
      atmospheric pressure or with equimolar amounts of diphenylacetylene lead to the
      compounds [Ni(iPr2Im)2(eta2-C2H4)] (2), [Ni(iPr2Im)2(eta2-C2Ph2)] (3), and
      [Ni(iPr2Im)2(CO)2] (4) in good yields. In all cases the [Ni(iPr2Im)2] complex
      fragment is readily transferred without decomposition or fragmentation. In the
      infrared spectrum of carbonyl complex 4, the CO stretching frequencies are
      observed at 1847 and 1921 cm(-1), and are significantly shifted to lower
      wavenumbers compared with other nickel(0) carbonyl complexes of the type
      [NiL2(CO)2]. Complex 1 activates the C--F bond of hexafluorobenzene very
      efficiently to give [Ni(iPr2Im)2(F)(C6F5)] (5). Furthermore, [Ni2(iPr2Im)4(cod)]
      (1) is also an excellent catalyst for the catalytic insertion of
      diphenylacetylene into the 2,2' bond of biphenylene. The reaction of 1 with
      equimolar amounts of biphenylene at low temperature leads to [Ni(iPr2Im)2(2,2'
      biphenyl)] (6), which is formed by insertion into the strained 2,2' bond. The
      reaction of diphenylacetylene and biphenylene at 80 degrees C in the presence of
      2 mol % of 1 as catalyst yields diphenylphenanthrene quantitatively and is
      complete within 30 minutes.

PMID- 15973749
TI  - Synthesis and optical resolution of a series of inherently chiral calix[4]crowns
      with cone and partial cone conformations.
AB  - A series of inherently chiral calix[4]arenes with cone and partial cone
      conformations and with crown ether moieties of variable size have been readily
      synthesized. By taking advantage of the carboxy appendage on the lower rim, these
      were condensed with the chiral auxiliary (S)-BINOL to form diastereomers which,
      in most cases, could be separated by preparative TLC, or more desirably, by
      column chromatography on silica gel (diastereomeric excess >99 % based on HPLC
      analysis). Seven enantiopure antipodes of inherently chiral calix[4]crowns were
      obtained after hydrolysis. It has been found that both the size of the crown
      moiety and alkylation of the last phenolic hydroxy group (accompanied with or
      without a change in the conformation) affect the separation of the diastereomers.

PMID- 15973750
TI  - Rigid nanoscopic containers for highly dispersed, stable metal and bimetal
      nanoparticles with both size and site control.
AB  - We demonstrate a novel strategy for the preparation of mesoporous silica
      supported, highly dispersed, stable metal and bimetal nanoparticles with both
      size and site control. The supporting mesoporous silica, functionalized by
      polyaminoamine (PAMAM) dendrimers, is prepared by repeated Michael addition with
      methyl acrylates (MA) and amidation reaction with ethylenediamine (EDA), by using
      aminopropyl-functionalized mesoporous silica as the starting material. The
      encapsulation of metal nanoparticles within the dendrimer-propagated mesoporous
      silica is achieved by the chemical reduction of metal-salt-impregnated dendrimer
      mesoporous silica by using aqueous hydrazine. The site control of the metal or
      bimetal nanoparticles is accomplished by the localization of inter- or
      intradendrimeric nanoparticles within the mesoporous silica tunnels. The size of
      the encapsulated nanoparticles is controlled by their confinement to the
      nanocavity of the dendrimer and the mesopore. For Cu and Pd, particles locate at
      the lining of mesoporous tunnels, and have diameters of less than 2.0 nm. For
      Pd/Pt, particles locate at the middle of mesoporous tunnels and have diameters in
      the range of 2.0-4.2 nm. The Pd and Pd/Pt nanoparticles are very stable in air,
      whereas the Cu nanoparticles are stable only in an inert atmosphere.

PMID- 15973751
TI  - Rare and diverse binding modes introduced through mechanical bonding.

PMID- 15973752
TI  - Cellular profiling of small-molecule bioactivities: an alternative tool for
      chemical biology.

PMID- 15973753
TI  - Direct catalytic enantioselective aza-Diels-Alder reactions.

PMID- 15973754
TI  - Electrochemical control of the photocurrent direction in intercalated DNA/CdS
      nanoparticle systems.

PMID- 15973755
TI  - An S-selective lipase was created by rational redesign and the enantioselectivity
      increased with temperature.

PMID- 15973756
TI  - Water-soluble photoluminescent silicon quantum dots.

PMID- 15973757
TI  - Chiral phosphine-olefin bidentate ligands in asymmetric catalysis: rhodium
      catalyzed asymmetric 1,4-addition of aryl boronic acids to maleimides.

PMID- 15973758
TI  - Artificial transcriptional activation domains.

PMID- 15973759
TI  - Bead-based cellular analysis, sorting and multiplexing.

PMID- 15973760
TI  - Dynamic concision for three-dimensional reconstruction of human organ built with
      virtual reality modelling language (VRML).
AB  - This research studies the process of 3D reconstruction and dynamic concision
      based on 2D medical digital images using virtual reality modelling language
      (VRML) and JavaScript language, with a focus on how to realize the dynamic
      concision of 3D medical model with script node and sensor node in VRML. The 3D
      reconstruction and concision of body internal organs can be built with such high
      quality that they are better than those obtained from the traditional methods.
      With the function of dynamic concision, the VRML browser can offer better windows
      for man-computer interaction in real-time environment than ever before. 3D
      reconstruction and dynamic concision with VRML can be used to meet the
      requirement for the medical observation of 3D reconstruction and have a promising
      prospect in the fields of medical imaging.

PMID- 15973761
TI  - Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for
      anticonvulsant activity.
AB  - OBJECTIVE: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo
      pentanoic acid) was designed and synthesized to meet the structural requirements
      essential for anticonvulsant activity. METHODS: All the compounds were evaluated
      for anticonvulsant activity. Anticonvulsant activity was determined after
      intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and
      subcutaneous metrazol (ScMet) induced seizure methods and minimal motor
      impairment was determined by rotorod test. RESULTS: A majority of the compounds
      exhibited significant anticonvulsant activity after intraperitoneal
      administration. In the present study 4-(4'-fluoro phenyl) levulinic acid
      semicarbazone emerged as the most active molecule, showing broad spectrum of
      activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was
      found to be inactive in all the screens. CONCLUSION: The results obtained
      validate the hypothesis that presence of an aryl group near the semicarbazone
      moiety is essential for anticonvulsant activity. The results also indicate that
      the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

PMID- 15973762
TI  - Effects of fructose-1,6-diphosphate on concentration of calcium and activities of
      sarcoplosnic Ca2+-ATPase in cardiomyocytes of Adriamycin-treated rats.
AB  - OBJECTIVE: To observe the effects of fructose-1,6-diphosphate (FDP) on serum
      levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB), as well as
      the concentration of calcium in cardiomyocytes (Myo[Ca(2+)]) and activity of
      sarcoplosnic Ca(2+)-ATPase (SRCa(2+)-ATPase) in Adriamycin (ADR)-treated rats.
      METHODS: Rats were intraperitoneally injected with ADR (2.5 mg/kg every other day
      for 6 times) and then with different dosages of FDP (every other day for twenty
      one times). Bi-antibodies sandwich Enzyme linked immune absorption assay (ELISA)
      was performed to detect serum level of cTnI. CK-MB was detected by monoclonal
      antibody, Myo[Ca(2+)] was detected by fluorescent spectrophotometry and the
      activity of SRCa(2+)-ATPase was detected by inorganic phosphate method. RESULTS:
      FDP (300, 600, 1200 mg/kg) significantly reduced the serum levels of cTnI and CK
      MB, while at the same time decreased calcium concentration and increased SRCa(2+)
      ATPase activity in cardiomyocytes of ADR-treated rats (P<0.01). CONCLUSIONS: FDP
      might alleviate the cardiotoxic effects induced by ADR through decreasing calcium
      level as well as increasing SRCa(2+)-ATPase activity in cardiomyocytes.

PMID- 15973763
TI  - A novel splice mutation of HERG in a Chinese family with long QT syndrome.
AB  - Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in
      which six ion-channel genes have been identified. The phenotype-genotype
      relationships of the HERG (human ether-a-go-go-related gene) mutations are not
      fully understood. The objective of this study is to identify the underlying
      genetic basis of a Chinese family with LQTS and to characterize the clinical
      manifestations properties of the mutation. Single strand conformation
      polymorphism (SSCP) analyses were conducted on DNA fragments amplified by
      polymerase chain reaction from five LQT-related genes. Aberrant conformers were
      analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was
      identified in this Chinese LQTS family, leading to the deletion of 11-bp at the
      acceptor splice site of Exon9 [Exon9 IVS del (-12-->-2)]. The mutation might
      affect, through deficient splicing, the putative cyclic nucleotide binding domain
      (CNBD) of the HERG K(+) channel. This mutation resulted in a mildly affected
      phenotype. Only the proband had a history of syncopes, while the other three
      individuals with long QT interval had no symptoms. Two other mutation carriers
      displayed normal phenotype. No sudden death occurred in the family. The 4
      affected individuals and the two silent mutation carriers were all heterozygous
      for the mutation. It is the first splice mutation of HERG reported in Chinese
      LQTS families. Clinical data suggest that the CNBD mutation may be less malignant
      than mutations occurring in the pore region and be partially dominant over wild
      type function.

PMID- 15973764
TI  - Immortalization of human umbilical vein endothelial cells with telomerase reverse
      transcriptase and simian virus 40 large T antigen.
AB  - OBJECTIVE: To establish normally conditionally-immortalized human umbilical vein
      endothelial cells (HUVECs) by ectopic expression of the human telomerase
      catalytic enzyme (hTERT) and simian virus 40 large T (SV40 LT) antigen. METHODS:
      Primary HUVECs were transfected with recombinant retrovirus containing hTERT or
      SV40 LT respectively. Subsequently drug resistant cell clones were screened and
      expanded for further studies. Endothelial cell biomarkers were confirmed by
      examination. RESULTS: The morphological phenotype of the transfected cells was
      similar to the non-transfected cells. Von Willebrand factor, hTERT and SV40 LT
      could be detected in transfected HUVECs. Moreover, higher telomerase activity in
      transfected cells was maintained for over 50 population doublings compared with
      only low level of endogenous telomerase transiently at early population doublings
      in primary HUVECs. When exposed to TNF-alpha (tumor necrosis factor-alpha), the
      expression of E-selectin in transfected cells was significantly up-regulated, but
      no alteration of endothelial lipase was found. CONCLUSION: Ectopic coexpression
      of hTERT and SV40 LT can effectively immortalize HUVECs without tumorigenicity in
      vitro. Immortalized HUVECs may be an ideal target of further molecular function
      studies.

PMID- 15973766
TI  - Is decompressive craniectomy for malignant middle cerebral artery infarction of
      any worth?
AB  - OBJECTIVE: Malignant middle cerebral artery (MCA) infarction is characterized by
      mortality rate of up to 80%. The aim of this study was to determine the value of
      decompressive craniectomy in patients presenting malignant MCA infarction
      compared with those receiving medical treatment alone. METHODS: Patients with
      malignant MCA infarction treated in our hospital between January 1996 and March
      2004 were included in this retrospective analysis. The National Institute of
      Health Stroke Scale (NIHSS) was used to assess neurological status on admission
      and at one week after surgery. All patients were followed up for assessment of
      functional outcome by the Barthel index (BI) and modified Rankin Scale (RS) at 3
      months after infarction. RESULTS: Ten out of 24 patients underwent decompressive
      craniectomy. The mean interval between stroke onset and surgery was 62.10 h. The
      mortality was 10.0% compared with 64.2% in patients who received medical
      treatment alone (P<0.001). The mean NIHSS score before surgery was 26.0 and 15.4
      after surgery (P<0.001). At follow up, patients who underwent surgery had
      significantly better outcome with mean BI of 53.3, RS of 3.3 as compared to only
      16.0 and 4.60 in medically treated patients. Speech function also improved in
      patients with dominant hemispherical infarction. CONCLUSION: Decompressive
      craniectomy in patients with malignant MCA infarction improves both survival
      rates and functional outcomes compared with medical treatment alone. A randomized
      controlled trial is required to substantiate those findings.

PMID- 15973765
TI  - Basic fibroblast growth factor alleviates brain injury following global ischemia
      reperfusion in rabbits.
AB  - The aim of this study was to explore the protective effect of basic fibroblast
      growth factor (bFGF) on brain injury following global ischemia reperfusion and
      its mechanisms. Brain injury following global ischemia was induced by four
      vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized
      into three groups: group A, only dissection of vessels; group B, intravenous
      infusion of normal saline after reperfusion for 6 h; group C, 30 microg/kg bFGF
      injected intravenously at the onset of reperfusion, then infused with 10
      microg/(kg.h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-8 (IL-8)
      were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after
      reperfusion. Brain water content was determined and cerebral histopathological
      damages were compared. NSE and S-100B were increased 1 h after reperfusion and
      reached their peaks 6 h after reperfusion, but were much higher in group B than
      those in group C 3, 6 h after reperfusion. In groups B and C, TNF-alpha was
      increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h
      after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion
      respectively. TNF-alpha and IL-8 at the time points of 1 h and 3 h and IL-1 at 3
      h and 6 h in group C were correspondingly lower than those in group B. These
      indices in group A were nearly unchanged. There were less severe cerebral
      histopathological damages in group C compared with group B, but no difference in
      brain water content. It could be concluded that bFGF alleviates brain injury
      following global ischemia and reperfusion by down-regulating expression of
      inflammatory factors and inhibiting their activities.

PMID- 15973767
TI  - Influence of CO2 pneumoperitoneum on intracellular pH and signal transduction in
      cancer cells.
AB  - OBJECT: The authors studied the influence of CO(2) pneumoperitoneum on
      intracellular pH and signal transduction arising from cancer cell multiplication
      in laparoscopic tumor operation. METHOD: They set up a simulation of
      pneumoperitoneum under different CO(2) pressure, and then measured the variation
      of intracellular pH (pHi) at different time and the activity of protein kinase C
      (PKC) and protein phosphatase 2a (PP2a) at the end of the pneumoperitoneum. After
      1 week, the concentration of cancer cells in the culture medium was calculated.
      RESULT: When the pressure of CO(2) pneumoperitoneum was 0, 10, 20, 30 mmHg
      respectively, the average pHi was 7.273, 7.075, 6.783, 6.693 at the end of the
      pneumoperitoneum; PKC activity was 159.4, 168.5, 178.0, 181.6 nmol/(g.min) and
      PP2a was 4158.3, 4066.9, 3984.0, 3878.5 nmol/(g.min) respectively. After 1 week,
      the cancer cells concentration was 2.15 x 10(5), 2.03 x 10(5), 2.20 x 10(5), 2.18
      x 10(5) L(-1). CONCLUSION: CO(2) pneumoperitoneum could promote acidosis in
      cancer cells, inducing the activation of protein kinase C and deactivation of
      protein phosphatase 2a, but it could not accelerate the mitosis rate of the
      cancer cells.

PMID- 15973769
TI  - Character of HBV (hepatitis B virus) polymerase gene rtM204V/I and rtL180M
      mutation in patients with lamivudine resistance.
AB  - OBJECTIVES: To investigate the relationship between HBV (hepatitis B virus)
      polymerase gene 180 and 204 sites mutation and lamivudine resistance. METHODS:
      One hundred forty-one patients with lamivudine resistance after lamivudine
      treatment and 60 chronic hepatitis B patients without lamivudine treatment were
      enrolled in this study. The serum HBV DNA mutation was analyzed by sequence
      detection via polymerase chain reaction (PCR). The sequences of the same patient
      were analyzed before and after lamivudine treatment. RESULTS: One hundred and
      nine lamivudine resistance patients had HBV YMDD (tyrosine-methionine-aspartate
      aspartate) mutation. Among them, 45 patients had rtL180M/M204V mutation (41.28%),
      28 patients had rtL180M/M204I mutation (25.70%) and 36 patients had rtM204I
      mutation (33.02%). There were 6 patients with rtL180M mutation in 32 lamivudine
      resistance patients. Sixty chronic hepatitis patients without lamivudine
      treatment had no mutations. CONCLUSIONS: HBV mutations, which play an important
      role in lamivudine resistance usually locate at polymerase gene 204 site; 180
      site mutation was also observed in these patients. Evaluation of the anti-virus
      therapy by surveillance of the two sites mutations is of importance.

PMID- 15973768
TI  - Screening the active constituents of Chinese medicinal herbs as potent inhibitors
      of Cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2
      kinase.
AB  - OBJECTIVE: To screen and evaluate the active constituents of Chinese medicinal
      herbs as potent inhibitors of Cdc25 phosphatase. METHODS: The affinity
      chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion
      protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used
      as the cell cycle-specific targets for screening the antimitotic constituents. We
      tested 9 extracts isolated from the Chinese medicinal herbs and vegetables
      including the agents currently used in cancer treatment by measuring the
      inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity
      of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay and flow cytometry. RESULTS: Cdc25A inhibitory
      activity and antitumor activity are detected in the extracts isolated from three
      Chinese medicinal herbs Agrimona pilosa; Herba solani lyrati; Galla chinesis.
      CONCLUSION: We found three extracts isolated from Chinese medicinal herbs have
      potential inhibitory activity of Cdc25 phosphatase using a highly specific
      mechanism-based screen assay for antimitotic drug discovery.

PMID- 15973770
TI  - Extracellular HIV Tat and Tat cysteine rich peptide increase CCR5 expression in
      monocytes.
AB  - In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat
      induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human
      monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat
      cysteine rich peptide increase CCR5 expression in human monocytes, and this
      activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5
      expression in monocytes. These results provide insight into a new mechanism by
      which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.

PMID- 15973771
TI  - Construction and identification of Fas-targeting siRNA-expressing plasmid.
AB  - OBJECTIVE: To study the therapeutic potential of Fas inhibition in different
      diseases, a Fas-targeting siRNA (small interfering)-expressing plasmid was
      constructed. METHODS: The U6 promoter cassette and siFas (small interfering RNA
      that inhibit Fas expression) template sequence were obtained by PCR method. They
      were cloned into modified pcDNA3.1. The resultant plasmid pU6-siFas was
      transfected into P815 cells with lipofectin2000 and selected under G-418
      containing culture medium. Fas inhibition in stably transfected cells was
      detected by immunocytochemistry. RESULTS: The plasmid pU6-siFas efficiently
      reduced the expression of Fas and conferred G-418 resistance in P815 cells.
      CONCLUSION: The successful construction of the siRNA expressing plasmid will
      facilitate the application of RNA interference technique and lay the foundation
      for further study of Fas inhibition in the treatment of different diseases such
      as aplastic anemia and acute liver failure.

PMID- 15973772
TI  - Patients' quality of life after laparoscopic or open cholecystectomy.
AB  - OBJECTIVE: This study was aimed at evaluating and comparing the quality of life
      in patients who underwent laparoscopic and open cholecystectomy for chronic
      cholecystolithiasis. METHODS: The study included 25 patients with laparoscopic
      cholecystectomy (LC group) and 26 with open cholecystectomy (OC group). The
      quality of life was measured with the Gastrointestinal Quality of Life Index
      (GLQI) preoperatively, thereafter regularly at 2, 5, 10 and 16 weeks after the
      operation. RESULTS: The mean preoperative overall GLQI scores were 112.5 and
      110.3 in LC and OC group respectively (P>0.05). In the LC group, the mean overall
      GLQI score reduced slightly to 110.0 two weeks after the operation (P>0.05). The
      LC group showed significant improvement in overall score and in the aspects of
      symptomatology, emotional and physiological status from 5 to 16 weeks
      postoperatively. In the OC group, the GLQI score reduced to 102.0 two weeks after
      surgery (P<0.05). Significant reductions were shown in the aspects of
      symptomatology, physiological and social status. The GLQI scores returned to the
      preoperative level of 115.6 ten weeks after the operation (P>0.05). The patients
      experienced significant improvements of GLQI sixteen weeks after OC operation
      (P<0.01~0.05). Within the 10 postoperative weeks, the LC group had significantly
      higher GLQI scores than the OC group (P<0.05). CONCLUSIONS: LC can improve the
      quality of life postoperatively better and more rapidly than OC. The assessment
      of quality of life assessment is a valid method for measuring the effects of
      surgical treatment.

PMID- 15973773
TI  - The treatment of relapsing primary nephrotic syndrome in children.
AB  - OBJECTIVE: To explore better therapy and reduce the rate of re-relapse of primary
      nephritic syndrome in children who had been treated with corticosteroids but
      relapsed. METHODS: Eighty relapsers were enrolled from Jan. 1994 to Apr. 2000,
      who were randomly divided into two groups. The treatment group (n=39) had been
      treated with tripterysium glucosides for three months, with the control group
      (n=41) members were treated with cyclophosphmide (CTX) by intermission
      intravenous pulse, with total dose of CTX not being more than 150 mg/kg.
      Prednisone, meanwhile, was given to both groups. The total treatment period of
      prednisone was prolonged by 12-18 months. RESULTS: After following up for 3-7
      years, the re-relapse rates of both groups were observed. The re-relapse rate of
      the treatment group was 28.2% to 29.3% in the CTX-controlled group. The re
      relapse rates between two groups were almost similar, and with no observed
      significant difference (P>0.05). The side effect of tripterysium glucosides was
      less than that of CTX. CONCLUSION: For the treatment of relapsing nephritic
      syndrome in children, the combination of tripterysium glucosides and prolonged
      corticosteroid therapy is as effective as the regimen of CTX plus prolonged use
      of prednisone.

PMID- 15973774
TI  - Study on the neurotoxic effects of low-level lead exposure in rats.
AB  - OBJECTIVE: To investigate effects of developmental lead exposure on nitric oxide
      synthase (NOS) activity in different brain regions and on N-methyl-D-aspartate
      (NMDA) receptor mRNA expression in the hippocampus of rats. On the basis of these
      observations, we explored possible mechanisms by which lead exposure leads to
      impaired learning and memorizing abilities in children. METHODS: A series of rat
      animal models exposed to low levels of lead during the developing period was
      established (drinking water containing 0.025%, 0.05% and 0.075% lead acetate).
      NOS activities in the hippocampus, the cerebral cortex, the cerebellum and the
      brain stem were determined with fluorescence measurement and levels of mRNA
      expression of the NMDA receptor 2A (NR2A) subunit and NMDA receptor 2B (NR2B)
      subunit in the rat hippocampus were measured with Retro-translation (RT-PCR).
      RESULTS: There were no differences in the body weight of rat pups between any of
      the groups at any given time (P>0.05). The blood lead level of Pb-exposed rat
      pups showed a systematic pattern of change: at 14 d of age, it was lower than
      that at 7 d of age, then rising to the peak level at 21 d and finally falling to
      lower levels at 28 d. The hippocampal NOS activities of lead-exposed groups were
      all lower than that of the control group on the 21st and 28th day (P<0.01). NOS
      activities in the cerebellum of lead-exposed groups were all lower than that of
      the control group on the 21st and 28th day (P<0.001) and the NOS activity of the
      0.025% group was significantly lower than that of the 0.05% and 0.075% groups on
      the 28th day (P<0.05). NOS activity in the cerebral cortex of the 0.075% group
      was significantly lower than that of the control, 0.025% and 0.05% groups on the
      four day spans (P<0.001). There was no significant difference of NOS activity in
      the brain stem between any lead-exposed group and the control group on the four
      day spans. In the 0.05% and the 0.075% groups, the level of NR2A mRNA expression
      was higher than that in the control group at 7 d and 14 d of age (P<0.05). In the
      0.025% group, the level of NR2A was found to be higher than that in the control
      group at 7 d of age only (P<0.05). No significant differences were found for the
      levels of NR2B mRNA expression between any of the groups at any given time.
      CONCLUSIONS: NOS activity in the hippocampus, the cerebral cortex and the
      cerebellum are inhibited by lead exposure. The degree of the inhibitory effect
      depends on the time span of exposure and the lead concentration. Developmental
      low-level lead exposure was found to raise the level of NR2A mRNA expression in
      the hippocampus of rats. Developmental low-level lead exposure does not affect
      the level of NR2B mRNA expression in the hippocampus.

PMID- 15973775
TI  - Expression of endothelial nitric oxide synthase and vascular endothelial growth
      factor in association with neovascularization in human primary astrocytoma.
AB  - OBJECTIVE: To investigate the relationship between the expression of endothelial
      nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and
      angiogenesis in primary astrocytoma. METHODS: Thirty-seven primary astrocytomas
      and 4 astrocytic hyperplasia samples were collected and divided into three groups
      according to histological grade. The expression of eNOS, VEGF and factor VIII
      related antigen (FVIIIRAg) were assayed by immunohistochemistry. Microvascular
      density was assessed by FVIIIRAg immunoreactivity. The intensity of
      immunoreactivity was graded according to the percentage of positive tumor cells.
      RESULTS: No eNOS and VEGF were expressed in the astrocytes and vascular
      endothelium in astrocytic hyperplasia. The expression of eNOS or VEGF was light
      in low-grade astrocytoma and strong in glioblastoma. eNOS expression in
      astrocytoma was very positively correlated with VEGF. eNOS and VEGF expression in
      anaplastic astrocytoma was median in contrast to the low grade astrocytoma and
      glioblastoma. Lower microvascular density was found in low grade astrocytoma than
      that in higher grade malignant ones. The expressions of eNOS and VEGF were
      correlated with microvascular density and tumor malignancy. CONCLUSION: This
      finding suggests that eNOS and VEGF may have cooperative effect in tumor
      angiogenesis and play an important role in the pathogenesis of primary
      astrocytoma.

PMID- 15973776
TI  - Effects of IGF-II on promoting proliferation and regulating nitric oxide synthase
      gene expression in mouse osteoblast-like cell.
AB  - OBJECTIVE: To investigate the effects of insulin-like growth factor II (IGF-II)
      on promoting cell proliferation, regulating levels of cellular nitric oxide (NO)
      and mRNA transcriptions of inducible nitric oxide synthase (iNOS) and endothelial
      NOS (eNOS) in mouse osteoblast-like cells. METHODS: Mouse osteoblastic cell line
      MC3T3-E1 was selected as the effective cell of IGF-II. After the cells were
      treated with IGF-II at different concentrations for different time duration, 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric
      assay was used to examine cell proliferation, and nitrate reductase method was
      applied to detect NO concentrations in cell culture supernatants and quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to
      determine transcription levels of cellular iNOS and eNOS mRNAs. RESULTS: After
      the MC3T3-E1 cells were treated with IGF-II at concentration of 1 ng/ml for 72 h,
      10 and 100 ng/ml for 24, 48 and 72 h respectively, all the MTT values increased
      (P<0.05 or P<0.01) with obvious dosage-time dependent pattern. NO levels of the
      MC3T3-E1 cells treated with 100 ng/ml IGF-II for 48 h, and with 1, 10 and 100
      ng/ml IGF-II for 72 h were remarkably lower than that of the normal control,
      respectively (P<0.05 or P<0.01). After the cells were treated with 100 ng/ml IGF
      II for 48 h cellular iNOS mRNA levels were significantly decreased (P<0.01). But
      the levels of eNOS mRNA in the cells treated with each of the used IGF-II dosages
      for different time duration did not show any differences compared with the normal
      control (P>0.05). CONCLUSION: IGF-II at different concentrations could promote
      proliferation of mouse MC3T3-E1 cell. This cell proliferation promotion was
      associated with the low NO levels maintained by IGF-II. Higher concentration of
      IGF-II could down-regulate iNOS gene expression at the level of transcription but
      not affect transcription of eNOS mRNA, which might be one of the mechanisms for
      IGF-II maintenance of the low NO levels in MC3T3-E1 cells.

PMID- 15973778
TI  - Bibliography. Current world literature. Food allergy.

PMID- 15973777
TI  - Breast cancer metastasis to the aortic vessel wall.

PMID- 15973780
TI  - Highlights of the ERS Task Force on pulmonary-hepatic vascular disorders (PHD).

PMID- 15973779
TI  - Liver disease as a major cause of death among HIV infected patients: role of
      hepatitis C and B viruses and alcohol.
AB  - BACKGROUND/AIMS: We analyzed the characteristics of HIV infected patients who
      died from liver disease, focusing on hepatitis virus co-infection. METHODS: One
      hundred and eighty-five French hospital departments involved in HIV/AIDS
      management prospectively notified all deaths occurring in 2000. Patients whose
      hepatitis C (HCV) and hepatitis B (HBV) serostatus was known were classified as
      being infected by HCV alone, HBV alone (HBsAg positive), both HCV and HBV, or
      neither HCB nor HBV. RESULTS: Among 822 HIV infected patients, 29% were infected
      by HCV alone, 8% by HBV alone, and 4% by both HCV and HBV. The most frequent
      causes of death were liver disease (31% of cases) and AIDS (29%) among HIV-HCV co
      infected patients, and AIDS (38%) and liver disease (22%) among HIV-HBV co
      infected patients. Liver disease was a more frequent cause of death among
      patients co-infected by both HCV and HBV (44% of cases). Hepatocellular carcinoma
      was present in 15% of patients who died from liver disease, and was associated
      with HBV co-infection. Nearly half the patients who died from liver disease had
      more than 200 CD4/mm3. CONCLUSIONS: Liver disease is now a leading cause of death
      among HIV-HCV co-infected patients and is becoming an important cause of death
      among HIV-HBV co-infected patients. The risk of death from liver disease is
      highest in patients co-infected by both HCV and HBV.

PMID- 15973781
TI  - Disorders of free sialic acid.

PMID- 15973783
TI  - The persistence of object file representations.
AB  - Coherent visual experience of dynamic scenes requires not only that the visual
      system segment scenes into component objects but that these object
      representations persist, so that an object can be identified as the same object
      from an earlier time. Object files (OFs) are visual representations thought to
      mediate such abilities: OFs lie between lower level sensory processing and higher
      level recognition, and they track salient objects over time and motion. OFs have
      traditionally been studied via object-specific preview benefits (OSPBs), in which
      discriminations of an object's features are speeded when an earlier preview of
      those features occurred on the same object, as opposed to on a different object,
      beyond general displaywide priming. Despite its popularity, many fundamental
      aspects of the OF framework remain unexplored. For example, although OFs are
      thought to be involved primarily in online visual processing, we do not know how
      long such representations persist; previous studies found OSPBs for up to 1500
      msec but did not test for longer durations. We explored this issue using a
      modified object reviewing paradigm and found that robust OSPBs persist for more
      than five times longer than has previously been tested-for at least 8 sec, and
      possibly for much longer. Object files may be the "glue" that makes visual
      experience coherent not just in online moment-by-moment processing, but on the
      scale of seconds that characterizes our everyday perceptual experiences. These
      findings also bear on research in infant cognition, where OFs are thought to
      explain infants' abilities to track and enumerate small sets of objects over
      longer durations.

PMID- 15973782
TI  - Mobilization for cervical cancer screening: lessons from a poor-urban Yoruba
      community in Nigeria.
AB  - Cervical cancer is a major public health problem worldwide and it remains one of
      the commonest malignancies in Nigeria. Screening remains the most effective tool
      for the detection of pre-invasive stages of cervical cancer, giving the
      opportunity for prompt and effective treatment before the emergence of invasive
      disease. In Nigeria, as in most developing countries, the concept of screening
      for cancer and its pre-emptive treatment is underdeveloped. The fact that the
      facilities and logistics for cervical cancer screening are generally located in
      the hospital setting, a place where one goes when ill, according to local
      beliefs, makes acceptance more difficult. That Nigeria urgently needs to set up
      or develop cervical screening programmes that will reach women outside the
      hospital setting in a culturally acceptable milieu is not in doubt. A community
      cervical screening survey for the prevalence of cervical intraepithelial
      neoplasia and HPV infection was initiated in Idikan, a poor-urban inner core area
      of Ibadan. The challenges and experiences encountered in the execution of the
      project which could serve as useful knowledge to those undertaking similar
      exercises, requiring mass mobilization for cancer screening of an uninformed
      group, are highlighted. Our experience in the course of this study is important
      as it brought out the probable influences of community dynamics and social
      organization in illness decisions and prescriptions for health operative in this
      particular population group. Cervical cancer screening programmes should
      therefore make provisions to accommodate the occasional outcomes as we had
      encountered. In addition, screening programmes in developing societies would
      require sensitive designs that should address the cultural attitudes, personal
      conflicts, expectations of treatment and overall context of preventive care.

PMID- 15973784
TI  - Simultaneous contralateral vestibular schwannoma and glomus jugulare tumor: a
      case report.
AB  - To the best of our knowledge, only 3 cases of a simultaneous vestibular
      schwannoma and a glomus jugulare tumor have been previously reported in the
      literature. In all 3 cases, the lesions were located on the same side. We report
      a new case of simultaneous vestibular schwannoma and glomus jugulare tumor that
      is unique in that the two lesions arose on opposite sides. The glomus tumor was
      treated with embolization followed by radiotherapy, while the schwannoma was
      managed via radiologic observation.

PMID- 15973785
TI  - Prediction methods for babies' birth weight using linear and nonlinear regression
      analysis.
AB  - The aim of this study is to determine more accurate prediction methods between
      linear and non-linear methods for prediction of babies' birth weight among
      maternal demographic characteristics. Three hundred pregnant women were included
      in the study. Blood glucose level before and after ingestion of glucose load,
      age, body mass index, % of change in weight during pregnancy, height, gestational
      age, parity, and fetal sex were collected as independent variables and baby birth
      weight as dependent variable. In linear regression, least squares estimation
      method was used to estimate parameters. Non-linear regression method was
      performed using neural network model with multilayer perceptrons, back
      propagation method was preferred as learning algorithm. Coefficient of
      determination, R2, of the linear regression equation was found 59.8% and the
      standard error of the estimate was calculated as 325.69 gr. In non-linear
      regression method R2 value was also found 59.8% and standard error of estimate
      was calculated as 320.30 gr. According to the results of the present study, one
      method is not significantly better than the other. When "accuracy in prediction"
      is aimed, it is better to use the two methods and compare the results, and then
      decide on the selection of the favourable method.

PMID- 15973786
TI  - Chris Beasley.

PMID- 15973788
TI  - Proceedings of the Joint International Tropical Medicine Meeting 2003 (JITMM
      2003). December 2-4, 2003. Bangkok, Thailand.

PMID- 15973787
TI  - Evaluation of transgenic cotton varieties and a glyphosate application on
      seedling disease incidence.
AB  - A study was conducted to determine whether stand densities of transgenic cotton
      (Gossypium hirsutum) varieties, with or without glyphosate, were similar to
      conventional varieties of the same lineage group in Georgia and Mississippi.
      Transgenic and conventional cotton varieties were placed into five lineage groups
      of related varieties and seedling disease was evaluated in three greenhouse tests
      and a field trial using Rhizoctonia solani AG-4. Seed vigor was determined by
      standard germination studies were conducted evaluating conventional and
      transgenic varieties of similar lineage. Results showed that no interactions
      occurred for the heights and dry weight data across treatments within the lineage
      groups in any of the experiments. No interactions were shown between stand
      densities at different inoculum rates and inoculated versus uninoculated pots
      (plots). Across all greenhouse studies, stand counts of PM 1220 were similar to
      the transgenic varieties PM 1220 RR and PM 1220 B/RR with or without a glyphosate
      application. In the field trial, PM 1220 B/RR + glyphosate had significantly
      lower stands than all other treatments expect PM 1220 RR (no glyphosate
      treatment) prior to and after glyphosate application. Stand densities for
      varieties within the lineage group DPL 5415 were also inconsistent when compared
      between the greenhouse and field trials with no apparent trends occurring.
      However, the Coker 312 varieties containing glyphosate tolerance had consistently
      lower stand counts compared to the conventional variety of Coker 312 but only
      during the greenhouse studies. Seed germination of Coker 312 could not be
      correlated with either the greenhouse or field trial data. In general, the
      commercially available varieties such as PM 1220, DPL 5690, DPL 5415, and DPL 50
      with glyphosate tolerance had similar stand count, height, and dry weight data
      when compared to the conventional varieties from the same lineage group
      regardless of a glyphosate application. When differences did occur, no consistent
      trends could be determined within these four lineage groups.

PMID- 15973789
TI  - Authority for practitioners to dispense or prescribe approved narcotic controlled
      substances for maintenance or detoxification treatment. Final rule.
AB  - DEA is amending its regulations to allow qualified practitioners not otherwise
      registered as a narcotic treatment program to dispense and prescribe to narcotic
      dependent persons Schedule III, IV, and V narcotic controlled drugs approved by
      the Food and Drug Administration specifically for use in maintenance or
      detoxification treatment. This Final Rule is in response to amendments to the
      Controlled Substances Act by the Drug Addiction Treatment Act of 2000 (DATA) that
      are designed to expand and improve treatment of narcotic addiction. This Final
      Rule is intended to accomplish the goals of DATA while preventing the diversion
      of Schedule III, IV, and V narcotic controlled drugs approved by the Food and
      Drug Administration specifically for maintenance / detoxification treatment.

PMID- 15973790
TI  - Proceedings of the 5th International Conference on Sustainable Techniques and
      Strategies in Urban Water Management (NOVATECH 2004). June 6-10, 2004. Lyon,
      France.

PMID- 15973791
TI  - A singular moment in time.

PMID- 15973792
TI  - Medicare seniors much less willing to limit physician-hospital choice for lower
      costs.
AB  - Elderly Americans are much less willing than working-age Americans to limit their
      choice of physicians and hospitals to save on out-of-pocket medical costs,
      according to a new national study by the Center for Studying Health System Change
      (HSC). Only 44 percent of seniors 65 and older were willing to trade broad
      provider choice to save money, compared with more than 70 percent of people aged
      18 through 34. Among seniors, those enrolled in Medicare health maintenance
      organizations (HMOs) were the most willing to limit choice of providers in return
      for lower out-of-pocket costs, while Medicare seniors with supplemental coverage
      were the least willing. Seniors with supplemental coverage account for nearly six
      in 10 Medicare seniors, and with nearly two-thirds of these seniors opposing
      provider choice restrictions, policy makers seeking to expand enrollment in
      Medicare Advantage managed care plans may face challenges.

PMID- 15973793
TI  - Tracking health care costs: spending growth stabilizes at high rate in 2004.

PMID- 15973794
TI  - The devil may be in the details: how the characteristics of SCHIP programs affect
      take-up.
AB  - In this paper, we explore whether the specific design of a state's program has
      contributed to its success in meeting two objectives of the Children's Health
      Insurance Program (SCHIP): increasing the health insurance coverage of children
      in lower income families and doing so with a minimum reduction in their private
      health insurance coverage (crowd-out). In our analysis, we use two years of
      Current Population Survey data, 2000 and 2001, matched with detailed data on
      state programs. We focus on two populations: the eligible population of children,
      broadly defined--those living in families with incomes below 300 percent of the
      federal poverty line (FPL)--and a narrower group of children, those who we
      estimate are eligible for Medicaid or SCHIP. Unique state program characteristics
      in the analysis include whether the state plan covers families; whether the state
      uses presumptive eligibility; the number of months without private coverage that
      are required for eligibility; whether there is an asset test; whether a face-to
      face interview is required; and specific outreach activities. Our results provide
      evidence that state program characteristics are significant determinants of
      program success.

PMID- 15973795
TI  - Needle exchange programs and drug infection behavior.
AB  - This study examines how drug injection and needle sharing propensities respond
      when a needle exchange program (NEP) is introduced into a city. I analyze 1989
      1995 Drug Use Forecasting data on adult male arrestees from 24 large U.S. cities,
      in nine of which NEPs opened during the sample period. After controlling for
      cocaine and heroin prices, AIDS prevalence, fixed effects for cities and years
      and city-specific time trends, the model indicates that the presence of a NEP is
      associated with declines of 13 percent in drug injection and 20 percent in needle
      sharing among drug injectors.

PMID- 15973796
TI  - Medical marijuana.

PMID- 15973797
TI  - Improving the lives of young people with disabilities.

PMID- 15973798
TI  - [Assessment of therapeutic effectiveness of Cefprozil in a short 5-day course of
      empirical antibiotic therapy in ambulatory patients with bacterial infections of
      the upper respiratory tract and otitis media].

PMID- 15973799
TI  - [Sleep-disordered breathing in children--the analysis of some diagnostic
      methods].

PMID- 15973800
TI  - Racism in psychiatry.

PMID- 15973801
TI  - Phenomenology of psychosis.

PMID- 15973802
TI  - The moral status of wrongful life claims.
AB  - A wrongful life action is a claim brought by a disabled child who asserts that
      but for a physician's negligence he or she would not have been born, thereby
      being spared the suffering of life. The action is inherently controversial
      because the alternative to an impaired life is non-existence. Lord Griffiths has
      described such claims as 'utterly offensive; there should be rejoicing that the
      hospital's mistake bestowed the gift of life upon the child.' This paper cuts
      through the rhetoric that the debate has generated and analyses whether there is
      a sound doctrinal basis for recognizing wrongful life actions.

PMID- 15973803
TI  - A pretty pass: when is there a right to die?
AB  - This paper, the 2002 Fison Memorial Lecture, reflects on the state of the law on
      the right to die, following the cases of Mrs Pretty and Ms B. Particular
      attention is drawn to a number of developments in the European Court of Human
      Rights.

PMID- 15973804
TI  - The greater good?: issues of proportionality and democracy in the doctrine of
      necessity as applied in Re A.
AB  - This article examines the criminal law doctrine of necessity as applied in the
      conjoined twins case (Re A (Children) (Conjoined Twins: Surgical Separation)
      [2000] 4 All ER 961). It determines that the public law principle of
      proportionality underlies the doctrine, but identifies the preservation of life
      as the guiding principle behind the Court of Appeal's use of necessity in Re A.
      The article is critical of this elevation of the preservation of life under the
      doctrine of necessity and argues for an alternative conception of necessity based
      upon fundamental constitutional principles such as human rights and democracy.
      The principle of democracy has particular pertinence to the issue of necessity
      because it may be endangered by this common law justificatory defence. This
      conflict between democracy and necessity, it is argued, further supports the need
      for the constitutional value of democracy to play a key role in any application
      of necessity in future cases.

PMID- 15973805
TI  - Liberty: human rights and mental health.
AB  - In this paper, Lord Phillips reflects on the present state of the law relating to
      mental health; he considers the place of the common law doctrine of necessity as
      the basis for the detention of patients; he reviews a number of issues arising
      from the jurisprudence of the European Court of Human Rights in Strasbourg and a
      number of recent decisions of the Court of Appeal. Finally, he considers the
      prospects for change in the law foreshadowed in the Government's White Paper on
      the Reform of Mental Health Law (2000).

PMID- 15973806
TI  - Diabetes mellitus: implications, costs and issues.

PMID- 15973807
TI  - Emerging epidemic of diabetes mellitus.

PMID- 15973808
TI  - The Caribbean Declaration on Universal Foot Care and Amputation Prevention.
      "Amputation is a tragedy not a treatment" the global village model.

PMID- 15973809
TI  - Vasculopathy in the diabetic foot.
AB  - This paper attempts to distil some of the results of vasculopathy studies
      performed on Jamaican diabetic clinic attendees. Doppler measurements of
      ankle/brachial pressure index (A/BI) revealed that 23% of the diabetics had
      peripheral occlusive arterial disease (POAD) which was mostly asymptomatic.
      Plethysmographic blood flow studies revealed a profound reduction in the
      vasodilatory response to increased flow demand. Prevalence of POAD determined by
      Doppler testing of A/BI reported by other researchers ranged from 13% in a large
      community study, one-third of whom were diabetic, to 47% in patients who had been
      diabetic for 20 years. Isolated posterior tibial disease has been reported to
      carry a three-fold risk of all cause mortality and a four-fold risk of coronary
      heart disease mortality. This underscores the need for regular Doppler A/BI
      testing in order to improve the recognition, and treatment of POAD, and prevent
      further cardiovascular morbidity and mortality.

PMID- 15973810
TI  - The diabetic foot: a major problem for the new millennium.

PMID- 15973811
TI  - The Caribbean experience with the diabetic foot management of the diabetic foot.
AB  - The foot complications of diabetic patients are one of the commonest and most
      devastating of medical problems that occurs in the Caribbean. The scale of the
      problem is reflected in the fact that, on average, 75% of the beds in the general
      surgical wards of the Queen Elizabeth Hospital in Barbados are occupied by
      patients with this problem. Of the patients admitted, a third lose a limb by
      amputation and another third of the patients lose toes or part of their feet and
      remain in hospital an average of two months as doctors struggle to prevent them
      losing their limbs. Half of the patients are in their 70s when they are admitted
      to hospital but 4 per cent are as young as thirty to forty years. It is clear to
      the surgeons who struggle to save the limbs of these patients that preventive
      care and early and aggressive intervention, when problems occur, are the best way
      to avoid prolonged hospitalization and loss of limb. The events that precipitate
      the problems often appear trivial to most people. a little nick cutting a nail or
      a callus, a crack under the toe, an ingrowing nail, stepping on a rock in the
      yard or, even more devastating, on a dirty or rusty nail. The diabetic's foot is
      more susceptible to injury, sepsis and gangrene because of an altered
      inflammatory response and an increased incidence of occlusive vascular disease
      and neuropathy. Injuries normally considered minor can threaten the limb in
      diabetics by rapid progression of necrosis along tissue planes. Prevention is of
      primary importance and patients need to be educated and to remind themselves over
      and over again to clean their feet daily, paying particular attention to the
      interdigital areas: looking at them to make sure that there is no swelling or
      cuts or change in colour. Looking is important since diabetics, especially those
      with neuropathy, cannot rely-on pain as a symptom of injury. Patients have to be
      trained to recognise and respond to the signs of injury and infection without
      relying on the signal of pain that they and the health care workers usually rely
      upon to assess the seriousness of most conditions. Diabetics should wear
      something on their feet at all times, in and out of the house. What is worn
      should have a good firm sole to prevent penetration. If a sandal is worn, it
      should be strapped on so that it does not slip off easily. If something goes
      wrong, or is noticed to be wrong with the feet, professional help should be
      sought the same day. Treatment and observation are needed on a daily basis. In
      order to try and save a limb, patients may need to have a series of minor
      operations and for those who are seen by surgeons early enough, four out of every
      five persons will have their limbs preserved. However, after the limb is saved,
      it is in greater danger for further problems and patients may require special
      shoes to prevent recurrence. The area of rehabilitation and prevention needs a
      great deal of improvement in the Caribbean for specialist orthotic advice and
      skills are scarce. Team work is essential for, by working together, patients,
      doctors, nurses, chiropodists and orthotic technicians can improve outcomes for
      the diabetic patient.

PMID- 15973812
TI  - Wound healing and care in the infected diabetic foot.
AB  - The care of the infected diabetic foot remains an area for continued research as
      we try to reduce the morbidity and mortality of this most prevalent disease
      process. None of the new and advanced products can take the place of proper
      assessment, timely, and adequate surgical intervention and control of the blood
      sugar; they are only adjunctive. The use of non-invasive investigative techniques
      such as magnetic resonance imaging and nuclear bone scan can help to confirm the
      presence of osteomyelitis which must be eradicated to accelerate the healing
      process. The gold standard for diagnosing vascular disease is angiography.
      Defective blood flow to the lower extremity must be corrected to ensure aequate
      blood supply and nutrients to the wound. In addition, good glucose control,
      adequate nutrition and strong psychological support will make a difference in
      healing these difficult wounds.

PMID- 15973813
TI  - Onychogryphosis and the involuted nail in diabetes mellitus.

PMID- 15973814
TI  - An approach to understanding and treating common foot problems in the diabetic
      population.
AB  - The goal of this paper is to provide an overview of common foot problems seen in
      diabetic individuals. Initial therapeutic intervention such as debridement ofpre
      ulcerative lesions may prevent limb-threatening ulcerations from occurring. It is
      also essential that an understanding of the foot deformity and imbalance
      responsible for the high ulcerating pressures be identified and addressed for
      long-term treatment of these patients. The nature of compensatory foot imbalance
      with recommended re-alignment and balance therapies to prevent pathologic foot
      compensation and principles of padding and specific off-loading techniques are
      highlighted. Evaluation and therapy of often neglected digital deformities and
      treatment of nail pathology are reviewed.

PMID- 15973815
TI  - The biomechanical management of diabetic foot ulcers.
AB  - The primary goal in the treatment of diabetic foot ulcers is to obtain wound
      closure as expeditiously as possible and prevent the recurrence of foot wounds
      due to neuropathy, foot deformity, and poor circulation. Interventions that bring
      about the quick resolution of afoot wound and reduce the rate of recurrence have
      been shown to lower the risk of developing a secondary infection and decrease the
      incidence of lower extremity amputation in the diabetic patient.

PMID- 15973816
TI  - Sir Philip Sherlock distinguish award--citation.

PMID- 15973817
TI  - Preventing amputations from diabetes mellitus: the Indian Health Service
      experience.
AB  - With the heavy burden of diabetes mellitus among American Indians and Alaskan
      Natives, lower-extremity amputation (LEA) has become a common complication. Rates
      of diabetes-related LEA are 2-3 times those observed in other diabetic
      populations. During the past 12 years, the Indian Health Service (IHS) has made
      LEA prevention a public health priority. From 1988 to 1992 screening criteria
      based on simple examinations were developed and validated in primary care
      Settings. Prevention efforts have focused on targeting high-risk individuals for
      self-care foot education, provision of protective footwear, and routine podiatry
      care. Follow-up studies in Alaska and northern Minnesota saw 25-50% reductions in
      LEA rates associated with these interventions. In settings where these efforts
      were augmented with system changes, such as team coordination, patient-tracking
      systems, comprehensive footcare practice guidelines, flowsheets, and outreach
      programmes, LEA incidence was reduced by 50-75%. Efforts are currently underway
      to disseminate system-based approaches for comprehensive diabetic footcare and to
      expand the availability of foot care resources to tribal communities served by
      the IHS.

PMID- 15973818
TI  - The medical management of diabetes mellitus with particular reference to the
      lower extremity: the Jamaican experience.
AB  - Predisposing factors for the diabetic foot include peripheral neuropathy,
      peripheral vascular disease (PVD), hyperglycaemia and increased duration of
      diabetes. From the records of patients admitted to the University Hospital of the
      West Indies with the diabetic foot, we reviewed the results of the microbiology
      of wound swabs from diabetic foot ulcers. We noted the high prevalence of P VD
      (66.6%), peripheral neuropathy (50%), hyperglycaemia (75.6%) and increased
      duration of diabetes (17.5 years). A history of past foot ulcers was common and
      87.2% had polymicrobial infection. The commonest organisms were gram positive
      organisms which were usually sensitive to the 2 antibiotic regimes that were
      commonly used. Euglycaemia, a favourable lipid profile, control of blood
      pressure, yearly foot examination and institution of measures to prevent foot
      trauma are important in the prevention of foot ulceration.

PMID- 15973819
TI  - The diabetic lower extremity--the South Asian experience.

PMID- 15973820
TI  - Chronic disease control and compliance--the HOPE worldwide Jamaica experience.
AB  - HOPE worldwide Jamaica has provided mobile curative and preventative services to
      fourteen rural government clinics since 1994. The patient records of 1,091
      chronic disease patients, aged >30 years between January and December 1999 were
      reviewed. They were all above 30 years of age with an average age of 64 years;
      81% were female and 60% were hypertensive, 16% diabetic and 24% had both diabetes
      and hypertension. There were 2,390 visits for hypertension, with an average of 2
      visits per patient. Thirty-four per cent of patients had BP of < or = 140/90 mmHg
      while 43% had BP <160/ 95 mmHg. Compliance was defined as daily consistency in
      taking prescribed medication. Forty-four per cent of hypertensives were non
      compliant at the time of their visit. Anti-hypertensive treatment included
      thiazide diuretics (65%), reserpine (50%), ACE inhibitors (30%) and alpha
      methyldopa (5%). There were 1,129 visits for diabetes, with an average of 2
      visits per patient. Twenty-four per cent of diabetic patients were controlled to
      fasting blood glucose FBG levels of <6.7 mmol/l and 38% controlled to (FBG)
      levels <8 mmol/l. Thirty per cent of diabetics were non-compliant at the time of
      their visit. The most frequently used oral hypoglycaemic agents were metformin
      (78%), glyburide (43%) and chlorpropamide (30%). Fourteen per cent of diabetics
      were on treatment with insulin 70/30 (12%) and lente insulin (2%).
      Electrocardiograms (ECG) were done on 24% (n=267) of patients in the previous two
      years. Thirty-six per cent had evidence of left ventricular hypertrophy and 15%
      had evidence of ischaemic heart disease. The level of blood pressure and blood
      glucose control is inadequate, despitethe provision of regular monitoring,
      surveillance and improved access to pharmaceuticals. It is perceived that poor
      socioeconomic conditions, lack of education, cultural beliefs, in addition to
      other factors, continue to militate against improved compliance and control.

PMID- 15973821
TI  - An interim report of an intervention strategy for diabetes care in Jamaica.
AB  - The high prevalence (17.9%) of diabetes mellitus and its attendant costs have
      been recognized for some time. The diabetic public has hitherto been too oriented
      to seeking health care at the secondary and tertiary health care centres; a much
      too costly approach. As a part of a wellness promotion thrust as well as an
      awareness and intervention strategy, a number of health care agencies have
      collaborated in a training programme of lay diabetes facilitators. This was
      intended to allow a domino effect of "each one teach one" within the community.
      This intervention programme was undertaken over an 18-month period. No
      significant changes were achieved in glycaemia levels. The impact on hospital
      admissions and community awareness is yet to be assessed. Laboratory results
      indicated good correlation between glycosuria and hyperglycaemia. This could
      influence the thrust in maintaining glycosuria assessment alongside blood glucose
      monitoring. This approach would have a cost benefit for government clinics
      islandwide. Whilst it may be difficult to identify any one parameter that may be
      responsible for change, it will be possible to assume that this intervention
      strategy, the only innovation in the health care delivery modalities, may have
      contributed.

PMID- 15973822
TI  - Evaluation of resin composite materials. Part II: in vivo investigations.
AB  - PURPOSE: To clinically evaluate two different resin-based composites (Solitaire I
      and Ariston pHc) in order to determine the minimum clinical evaluation time
      needed to detect critical signs of failure. METHODS: In a controlled prospective
      clinical study, 99 cavities (30 Class I, 69 Class II) in 31 patients were
      restored (50 Ariston pHc without enamel etching and rubber dam, 49 Solitaire I
      restorations with total etching and rubber dam) and clinically investigated at
      baseline, after 6, 12, and 24 months. RESULTS: After 2 years of clinical service,
      49 restorations (Ariston pHc: n = 38, Solitaire: n = 11) had to be replaced. The
      majority of failures occurred after more than 1.5 years. The reasons for
      replacement were differently distributed in both groups (Ariston pHc: 28 tooth
      fractures, 3 gap formations, 5 hypersensitivities, 1 bulk fracture, 1 marginal
      fracture. Solitaire: 5 gap formations, 1 hypersensitivity, 3 bulk fractures, 1
      wear of the restorative material, 1 void in the restoration). Forty-four
      restorations were still in function after 2 years (overall failure rate after 2
      years: 14%; Ariston pHc: 17%; Solitaire: 7%; survival analysis algorithm
      according to Kaplan/Meier). Comparing the materials, no statistical differences
      were evident except for the criteria "integrity tooth" (= tooth fracture or
      cracks) and "hypersensitivity" (from the 12-month recall; Mann-Whitney U-test; P<
      0.05). In both cases of significant difference, Ariston pHc exhibited inferior
      results. After 2 years, only three teeth restored with Ariston pHc did not show
      considerably cracked enamel. The additional marginal analysis showed
      statistically significant differences for both materials regarding the criteria
      "perfect margin" (decrease), "gap formation" (increase), and "negative step
      formation" (increase; P< 0.05; Friedman 2-way ANOVA) between the four recalls.
      Therefore, a 2-year in vivo evaluation should be recommended prior to marketing a
      dental restorative material.

PMID- 15973823
TI  - Application of a preliminary light-curing unit for enhanced bonding between a
      gold alloy and veneering materials.
AB  - PURPOSE: To evaluate the effectiveness of a preliminary light-curing unit when it
      was used in a procedure to bond veneering material to metal. METHODS: Two light
      activated composite materials (Artglass and Cesead II) were separately placed
      onto gold alloy disks (Pontol LFC), and polymerized using one of the following
      three methods: (1) exposure with a high-intensity laboratory light-curing unit
      (Hyper LII) for 90 seconds; (2) exposure with a preliminary light-curing unit
      (Targis Quick) for 20 seconds, followed by exposure with the high-intensity unit
      for 90 seconds; and (3) exposure with the preliminary unit for 90 seconds,
      followed by exposure with the high-intensity unit for 90 seconds. Shear bond
      strengths were determined and compared by analysis of variance and post-hoc
      multiple comparison intervals. The curing depths of the two materials polymerized
      with the two curing units were determined using a scraping technique described by
      the International Organization for Standardization (ISO) 4049 with the aim of
      evaluating the difference in curing performance between the two units. RESULTS:
      The group polymerized using the preliminary unit for 90 seconds showed
      statistically improved bond strengths over the group polymerized without the
      preliminary unit (P < 0.05) regardless of the materials. Regarding the Cesead II
      material, both groups polymerized using the preliminary unit also indicated
      significantly improved bond strength compared with the group polymerized with
      high-intensity only. Also, curing depth results revealed that the high-intensity
      unit demonstrated greater curing performance than the preliminary unit for both
      types of materials examined.

PMID- 15973824
TI  - Effects of delayed microbial analysis of dental unit water line specimens.
AB  - PURPOSE: Monitoring microbial concentrations in water emitted from dental unit
      water lines (DUWL) is an important safety procedure. Improper handling of test
      water specimens could give incorrect results. Thus, the objective of this study
      was to measure the effects delayed culturing might have on DUWL specimens.
      METHODS: First, 100 mL water specimens were obtained from 10 different handpiece
      service lines within the School. All units had independent water systems, used DI
      (deionized water) water and were routinely cleaned using an alkaline peroxide
      based product. Two specimens of 10 mL were removed from the bottles and placed
      into individual sterile conical tubes. One set of tubes was processed
      immediately. 0.05 mL of sterile 1.0% (w/v) sodium thiosulfate solution was added
      to undiluted and diluted (1:10 and 1:100 with sterile DI water) specimens. After
      mixing, specimens were spiral plated onto duplicate R2A plates and incubated at
      21degrees C for 7 days. Colonies were then counted and the cfu/mL of each
      original specimen determined. Another set of tubes was placed into a shipping
      envelope and mailed out to the School. Upon receipt, the tubes were processed as
      described above. The remaining 80 mL of water in the collection bottles were
      divided equally into new sterile tubes. One tube was left at 21 degrees C, while
      the other was placed into a 37 degrees C incubator. Aliquots were processed
      immediately and then after 1, 3 and 7 days. Next, 30 mL water specimens were
      obtained from 15 handpiece service lines in three outside clinics. All units had
      independent water systems, used DI water and were routinely cleaned with an
      alkaline peroxide-based product. Specimens were then divided equally into three
      sterile conical tubes. One of the tubes was transported (at 4 degrees C) to the
      laboratory and immediately processed as described. At the collection site, the
      second tube was placed into a padded envelope and mailed back to the School. The
      third tube was returned by overnight delivery using a Cool Pack type container.
      Upon receipt, all the tubes were processed as described previously. RESULTS: The
      10 handpiece waterline specimens processed immediately ranged from 0 to 1000
      cfu/mL. Holding specimens at 21 degrees C produced radically higher bacterial
      counts (1540-866,000 cfu/mL) in water from 90% of the handpieces. Holding at 37
      degrees C produced unacceptably high bacterial counts in only 50% of the
      handpiece specimens. Mailed specimens were cultured 5 days after collection and
      water of unacceptable quality water was noted in 70% of the specimens. In another
      experimental set, mailed specimens arrived after 72 hours and were an average of
      20 degrees C. Express sent specimens came the next morning at an average
      temperature of 4.5 degrees C. Only one waterline specimen processed immediately
      contained more than 500 cfu/mL. In contrast, 80% of specimens returned by post at
      ambient temperature had unacceptably high bacterial counts (780-376,000 cfu/mL).
      Express sent specimens produced the same results as those processed immediately.

PMID- 15973825
TI  - Effect of acidulated phosphate fluoride (APF) gel on the adherence of cariogenic
      bacteria to resin composites.
AB  - PURPOSE: To evaluate the effect of 1.23% acidulated phosphate fluoride (APF) and
      the subsequent polishing on the in vitro adherence of mutans streptococci to
      resin composites in a model that simulated the oral cavity conditions. METHODS:
      Samples of light-curing resin-based composites (Z100 and Z250) were treated with
      1.23% APF gel (Sultan) for 1 minute and polished subsequently with Sof-Lex disks.
      The bacterial adherence of Streptococcus mutans and Streptococcus sobrinus to the
      APF gel treated resin samples and the subsequent polished samples were analyzed
      and compared with the adherence to the non-treated controls. RESULTS: The 1.23%
      APF gel caused a significant increase in the adherence of Streptococcus mutans
      and Streptococcus sobrinus. The increasing rate of the bacterial adherence to
      resin composites after APF treatment ranged from 73.5% to 167% and differed
      according to the bacterial strains. A decrease in the adherence of the bacteria
      was found after subsequent polishing with Sof-Lex disks.

PMID- 15973826
TI  - Surface characterization of modern resin composites: a multitechnique approach.
AB  - PURPOSE: To characterize the surface properties of some modern resin composites
      employing a series of physicochemical methods. METHODS: Specimens from three
      microhybrid (Palfique Estellite-PE, Z250 Filtek-ZF, Tetric Ceram-TC) and one
      nanofilled (Supreme Filtek-SF) conventionally photo-cured resin composites
      polished with Soflex disks were studied for the following properties: Surface
      chemical composition and degree of C=C conversion (FTIR), surface energetics
      (contact angles), surface texture (AFM), surface roughness (AFM, stylus
      profilometry) and gloss (60 degrees-, 20 degrees-angle specular gloss). RESULTS:
      Polar and non polar molecular groups were identified in all products including NH
      and CONH (SF, ZF, TC). SF and ZF demonstrated higher conversion than PE and TC
      (P< 0.05). No significant differences (P> 0.05) were found in critical surface
      tension, total work of adhesion and its polar and dispersion components, the
      latter being the highest in all products. AFM showed the smoothest surface
      texture in PE. The ranking of Sa, Sq, Ra and Rz roughness parameters was
      PE<SF<ZF, TC (P< 0.05). 20 degree-angle gloss measurements (PE, SF>ZF>TC, P<
      0.05) were more sensitive than 60 degree-angle measurements (PE, SF>TC, P< 0.05)
      in revealing gloss differences. A positive correlation was found between Sa and
      Ra and a negative one between Sa and 20 degree-angle gloss.

PMID- 15973827
TI  - Sports drinks and dental erosion.
AB  - PURPOSE: To discuss the composition and rationale for the use of sports drinks
      along with recent studies investigating the relationship between sports drinks
      and dental erosion. METHODS: A review of the literature of sports drinks and
      dental erosion was done. RESULTS: For most athletes and individuals engaged in
      physical activity, the use of sports drinks does not provide a benefit over
      water. Furthermore, although there is much in vitro evidence that acidic drinks
      such as wine, fruit juices and carbonated soft drinks have erosive potential and
      there are relationships between consumption of these drinks and erosion, only one
      study has reported an association between sports drinks and dental erosion. Other
      factors such as drinking habit and salivary production may be more important
      determinants of dental erosion.

PMID- 15973828
TI  - The validity of reported tensile bond strength utilizing non-standardized
      specimen surface areas. An analysis of in vitro studies.
AB  - PURPOSE: To assess and discuss the true value and perceived relevance of present
      day dental adhesive tensile bond strength studies. There are flaws and
      inconsistencies present in the data due to the inherent variations in testing
      methods, conditions, and types of samples prepared. In particular, surface areas
      of specimens need to be standardized. This review considers the significant
      impact of different surface areas of tooth specimens utilized in testing.
      RESULTS: On review of the data, relatively higher MPa values do not necessarily
      indicate improved dental adhesive products or procedures.

PMID- 15973829
TI  - Effect of filler loading on resin cement bonding to silanized buildup composites.
AB  - PURPOSE: To determine the effects of silanation for core buildup composites on
      bond strength of resin cement. METHODS: Three core buildup composites including
      FluoroCore LV, Core Restore, and Clearfil Photo Core, of which filler loadings
      were 65 wt%, 74 wt%, and 83 wt% respectively, were used. All composite specimens
      were randomly divided into four surface treatment groups of eight each as
      following; 1) 600-grit ground only, 2) 600-grit ground plus silanation, 3) 600
      grit ground plus air-particle abrasion, 4) air-particle abrasion plus silanation.
      Following these treatments, 4-META/MMA-TBB resin (C&B Metabond) was bonded to the
      specimen surfaces. Completed specimens were stored in 37 degree C water for 24
      hours, and then thermocycled 20,000 times (4 degree C - 60 degree C) before shear
      bond strengths were tested. Data were analyzed by two-way ANOVA and Scheffe's
      test for statistical significance (P < 0.05). RESULTS: Clearfil Photo Core, of
      which filler loading was the highest among the resin composites tested, treated
      with air-particle abrasion plus silanation obtained the highest bond strength.
      However, silanation alone was not effective for improving the bond strength.

PMID- 15973830
TI  - Effect of ultrasonic scaling on salivary lactate dehydrogenase.
AB  - PURPOSE: To determine Lactate Dehydrogenase Activity (LDHA) in whole saliva in
      individuals with periodontal disease and the effect of ultrasonic scaling on this
      enzyme activity. METHODS: A study group of 50 patients with PD (Community
      Periodontal Index of Treatment Needs > or = 3) was selected at random. Half of
      the patients (n=25) received ultrasonic periodontal treatment (Group 1). In the
      other 25 patients with PD the ultrasonic scaling was not performed (Group 2). A
      control group was selected (Group 3) consisting of 25 adults without PD
      (Community Periodontal Index of Treatment Needs = 0), with age and gender
      distribution similar to the study group. LDHA determinations were carried out
      with a Cobas Mira Plus II autoanalyzer pursuant to the recommendations of the
      French Society of Clinical Biology. A baseline determination of LDHA was carried
      out on all the participants and a second determination was performed 3 months
      later. RESULTS: Baseline determination of LDHA was higher in patients with PD
      than in the control group. These differences were statistically significant (P<
      0.001). LDHA was significantly reduced in patients with PD after ultrasonic
      scaling with respect to baseline determination (P< 0.0001). LDHA differences
      between Groups 2 and 3 were statistically significant (P< 0.0001), but it was not
      so between Groups 1 and 3.

PMID- 15973831
TI  - Plaque removal efficacy of a prototype power toothbrush compared to a control
      manual toothbrush.
AB  - PURPOSE: To compare the plaque removal efficacy of a control manual toothbrush
      (Lion Dentor Systema) to this prototype power toothbrush (Blend-a-Med Power)
      following a repeated single use study design. In addition, this paper reports the
      results of a study examining the relative plaque removal efficacy of the control
      manual toothbrush to nine representative manual toothbrushes. METHODS: This study
      was a randomized, controlled, examiner-blind, 6-period crossover design which
      examined plaque removal with the two toothbrushes following a single use in 86
      completed subjects. Plaque was scored before and after brushing using the Turesky
      Modification of the Quigley-Hein Index. A second 10-period crossover study was
      conducted to index the relative plaque removal performance of the control manual
      toothbrush (Lion Dentor Systema) to nine representative manual toothbrushes.
      RESULTS: Baseline plaque scores were 2.322 and 2.305 for the prototype power
      toothbrush and control toothbrush treatment groups, respectively. With respect to
      all surfaces examined, the prototype power toothbrush delivered an adjusted (via
      analysis of covariance) mean difference between baseline and post-brushing plaque
      scores of 0.633 while the control toothbrush delivered an adjusted mean
      difference of 0.576. The experimental toothbrush group, on average, had a 9.9%
      larger plaque removal score than the control toothbrush. These results were
      statistically significant (P= 0.014). Similar results were observed on buccal and
      lingual surfaces. In addition, results from the study comparing manual
      toothbrushes showed that the control manual toothbrush had similar plaque removal
      scores, not statistically significantly different, relative to nine
      representative manual toothbrushes.

PMID- 15973832
TI  - Effects of pre- or post-application of calcium chloride on occluding ability of
      potassium oxalate for the treatment of dentin hypersensitivity.
AB  - PURPOSE: To evaluate whether calcium ion supply using 1-6 mol/L CaCl2 solution
      could enhance the occluding ability of dentin tubules with 30% potassium oxalate
      treatment. METHODS: Calcium chloride solution (1-6 mol/L) was applied to dentin
      disks before or after application of 30% potassium oxalate solution. Occluding
      ability after potassium oxalate treatment was evaluated with scanning electron
      microscopic (SEM) observation and measurement of dentin permeability. In
      addition, the composition of the precipitate formed when mixing potassium oxalate
      and calcium chloride was analyzed with a powder x-ray diffractometer (XRD).
      RESULTS: SEM observations revealed that the dentin tubules were occluded
      homogeneously and completely with the precipitate when calcium chloride solution
      was applied before or after potassium oxalate treatment. However, the depth of
      the precipitate in dentin tubules from the dentin surface became shallower when
      pre-treated with calcium chloride before potassium oxalate. Although dentin
      permeability was greatly reduced in both groups, no significant difference could
      be observed between samples with and without calcium chloride application.

PMID- 15973833
TI  - Conversion of one-step to two-step self-etch adhesives for improved efficacy and
      extended application.
AB  - PURPOSE: One-step self-etch adhesives have restricted use due to their acid-base
      incompatibility with autocured composites and their behavior as permeable
      membranes after polymerization. This study examined the feasibility of their
      conversion to two-step self-etch adhesives via the adjunctive use of a non
      solvented, relatively hydrophobic resin coating. METHODS: iBond, Xeno III and
      Adper Prompt were used either in multiple coats, or in a single coat followed by
      the use of a layer of Scotchbond Multi-Purpose Plus bond resin for coupling to
      light- and auto-cured composites. Four types of experiments were performed.
      Bonded specimens were examined with TEM after immersion in an ammoniacal silver
      nitrate tracer. Fluid flow measurements of iBond were conducted using the two
      application protocols to compare the permeability of the bonded dentin with the
      original smear layer. Permeability of vital dentin bonded with both application
      protocols were compared for the transudation of dentin fluid across the bonded
      dentin. Microtensile bond strengths of dentin bonded with the two protocols were
      examined for their compatibility with an auto-cured composite. RESULTS: The
      results of the four experiments were complementary. iBond and Xeno III exhibited
      "apparent incompatibility" to auto-cured composites that resulted from their
      inherent permeability. This was confirmed by the presence of dentin fluid
      transudate on the adhesive surfaces when they were bonded to vital dentin.
      Conversely, Adper Prompt exhibited "true incompatibility" to auto-cured
      composites that was caused by adverse acid-base interaction, masking the inherent
      permeability of this adhesive. "True" and "apparent" incompatibility issues were
      eliminated upon their conversion to two-step self-etch adhesives.

PMID- 15973834
TI  - Clinical performance of a self-etching adhesive at 18 months.
AB  - PURPOSE: To test the null hypothesis that beveling and/or etching enamel would
      not affect the 18-month clinical performance of the self-etching adhesive
      Clearfil SE Bond (CSEB) in noncarious cervical lesions (NCCL). METHODS: With
      Institutional Review Board approval, 34 patients were enrolled in this study. A
      total of 120 NCCL was selected and assigned to four groups: (1) CSEB was applied
      without any cavity preparation; (2) CSEB was applied after beveling enamel; (3)
      CSEB was applied after etching enamel for 15 seconds with 35% phosphoric acid;
      (4) CSEB was applied after beveling and etching enamel. A microfilled composite
      resin was used for all restorations. RESULTS: At 6 months after initial
      placement, 120 restorations (a 100% recall rate) were evaluated. At 18 months, 87
      restorations (a 72.5% recall rate) were available for evaluation. A survival rate
      of 100% was measured for all groups at both 6 and 18 months. Sensitivity to air
      decreased significantly only for Group 3 (no bevel+acid etch) from baseline to 18
      months without statistical changes from 6 months to 18 months. None of the other
      parameters resulted in significant differences for any of the four groups.
      However, when data were pooled, both the overall marginal discoloration and the
      overall marginal adaptation were significantly worse at 18 months than at
      baseline, while sensitivity to air decreased significantly from baseline to 18
      months. The 18-month survival rate of the self-etching adhesive Clearfil SE Bond
      was not improved by enamel bevel or by enamel etching. Both overall marginal
      adaptation and overall marginal discoloration were worse at 18 months than at
      baseline. .

PMID- 15973835
TI  - Cure kinetics of composites using video imaging.
AB  - PURPOSE: To study the rate of curing, three composites, Heliomolar (Vivadent),
      Z100 (3M), and Renew (Bisco) were investigated METHODS: Volumetric shrinkage was
      measured at 25 degrees C using the Acuvol with an RG610 red filter. The dynamic
      measurements were made in the single view mode. RESULTS: Detailed kinetic studies
      for Renew determined the effect of varying the light intensity (100mW - 500mW)
      and irradiation time (3 seconds - 30 seconds) on the rate of curing. A
      measurement of the gel time of composites and a kinetic constant is reported.
      ANOVA followed by a Fisher's LSD test and a Kruskall-Wallis test were used for
      analysis of the data. The gel times follow the order of Heliomolar > Renew > Z100
      at 20 seconds and 500 mW. Irradiation time had no significant effect on the gel
      time of Renew. Light intensity had a significant effect on the gel time of Renew.

PMID- 15973836
TI  - Communication: whose problem is it?

PMID- 15973837
TI  - Reader comments on patient-specific vaccine therapy for non-Hodgkin lymphoma.

PMID- 15973838
TI  - Rectovaginal fistulas.

PMID- 15973839
TI  - My ear hurts: otitis media in the oncology setting.

PMID- 15973840
TI  - Communication in oncology care: the effectiveness of skills training workshops
      for healthcare providers.
AB  - Communication skills are the cornerstone of the patient-provider relationship in
      cancer care. Lack of these skills can diminish patient disclosure, increase
      patient anxiety, and decrease satisfaction with care. The purpose of this article
      is to evaluate the literature regarding the efficacy and outcomes of
      communication skills training programs for healthcare providers in oncology.
      Using four databases, the author found 21 research articles about communication
      skills training programs for healthcare providers in oncology. The majority of
      published studies involved training programs for experienced clinicians (i.e.,
      physicians, nurses, nurse practitioners, physician assistants) in oncology care.
      Programs varied in length from 18-105 hours and evaluated communication skills,
      patient satisfaction and anxiety, and provider confidence and perceived stress.
      Specific communication skills and provider confidence were statistically improved
      in 19 of 21 studies. Follow-up data showed maintenance of some skills and
      attrition of others. Longer programs with consolidation workshops are seen as
      more effective.

PMID- 15973841
TI  - You are special: recognizing the gifts you bring to oncology nursing.
AB  - To raise awareness about the need to recognize and celebrate the unique gifts and
      qualities nurses bring to oncology, the Oncology Nursing Society (ONS) Nominating
      Committee thought that discussing the many contributions of oncology nurses would
      be enlightening and empowering. This article originally was offered by the
      authors as a presentation at the ONS 29th Annual Congress in May 2004.

PMID- 15973842
TI  - Breast cancer chemoprevention: a review of selective estrogen receptor
      modulators.
AB  - Breast cancer is the most common cancer diagnosis among women in the United
      States. Chemoprevention plays an important role for women at high risk for
      developing breast cancer. The use of selective estrogen receptor modulators
      (SERMs) tamoxifen and raloxifene has demonstrated mixed results in breast cancer
      prevention clinical trials. In the United States, tamoxifen is approved for use
      for breast cancer prevention in women at high risk. The continued development of
      SERMs with improved side-effect profiles is needed. Oncology nurses play a
      pivotal role in helping patients to understand the current status of breast
      cancer prevention as well as the future direction of research.

PMID- 15973843
TI  - Hypersensitivity reactions to oxaliplatin: what nurses need to know.
AB  - Colorectal cancer (CRC) is the third-leading cause of cancer death in the United
      States. With the advent of new chemotherapy drugs, such as oxaliplatin, for CRC,
      disease-free and long-term survival has improved in this patient population. As
      oxaliplatin use increases, more hypersensitivity reactions may be expected. The
      etiology of these reactions is unclear but may be a combination of immunologic
      responses. Pretreatment, treatment, and desensitization protocols are available
      to prevent and treat hypersensitivity reactions. Nurses' rapid assessment and
      management of infusion-related hypersensitivity reactions are vital to ensuring
      the safe administration of oxaliplatin.

PMID- 15973844
TI  - Cetuximab: adverse event profile and recommendations for toxicity management.
AB  - Cetuximab (Erbitux, IMC-C225, ImClone Systems Incorporated, New York, NY) is a
      monoclonal antibody targeted to the epidermal growth factor receptor. Expression
      of the epidermal growth factor receptor is associated with disease progression,
      poor survival, poor response to therapy, and the development of resistance to
      therapy in many solid tumors. Cetuximab blocks the binding of natural ligands to
      the epidermal growth factor receptor, thus inhibiting oncogenic processes
      associated with its activation. Infusion reactions, acneform skin rash, and nail
      disorder are the most clinically relevant adverse events observed. Because
      infusion reactions can be life threatening when severe, nurses must administer
      prophylactic treatment with an H1 antagonist prior to infusion and actively
      manage cetuximab-related infusion reactions when they occur. Management of
      infusion reactions typically includes vigilant patient monitoring, appropriate
      medical supervision, readily available resources for the treatment of infusion
      reactions, and initiation of institution- or practice-specific protocols when
      necessary. Acneform skin rash is the most common adverse event, but severe (grade
      3 or 4) rash requiring interruption of treatment is not common. Topical and
      systemic antibiotic therapies may be administered to reduce symptoms. Nail
      disorder typically is mild to moderate and is observed infrequently; this also
      may be treated with systemic and topical antibiotics. Overall, the safety profile
      of cetuximab is favorable compared to that typically seen with chemotherapeutic
      agents. The acneform skin rash and nail disorder, which may affect quality of
      life, rarely threaten the general well-being of patients and typically are
      manageable.

PMID- 15973846
TI  - A day in the lives of Tuong-Vi Ho and Dawn P. Murphy, nurse practitioners.

PMID- 15973845
TI  - Radiofrequency ablation: a nursing perspective.
AB  - Radiofrequency ablation (RFA) has emerged as a safe and predictable technology
      for treating certain patients with cancer who otherwise have few treatment
      options. Nurses need to be familiar with all phases of the RFA procedure to
      create an optimal environment for patients. This article offers a brief review of
      the RFA procedure and nurses' responsibilities in caring for these patients.
      Before RFA, nurses should focus on patient education and aggressive hydration.
      During the procedure, nurses can prevent injury by placing grounding pads
      appropriately, monitoring vital signs, and medicating patients as needed. After
      RFA, nurses should assess the skin puncture site, provide adequate pain relief,
      and, again, hydrate patients. Nurses who care appropriately for RFA recipients
      may help to improve patient outcomes and make an otherwise frightening procedure
      more comfortable.

PMID- 15973847
TI  - Exposed bone in oral cavities.

PMID- 15973848
TI  - Navigating external beam radiation therapy for head and neck cancer.

PMID- 15973849
TI  - Ovarian cancer screening: are there any options?

PMID- 15973850
TI  - Establishing an integrative medicine center.
AB  - Cast a wide net, and include internal and external customers in planning. Keep
      communicating about the results of the needs assessment and each plan as it
      emerges. Ask everyone involved for feedback. Employ clinicians with experience
      and solid credentials, and have a plan for measuring outcomes.

PMID- 15973851
TI  - MammoSite Radiation Therapy System.

PMID- 15973852
TI  - Radical prostatectomy: what you need to know.

PMID- 15973853
TI  - Connectedness through time and space, mind and heart.

PMID- 15973855
TI  - Connectivity and healing: some hypotheses about the phenomenon and how to study
      it.

PMID- 15973854
TI  - Methodological challenges in meditation research.
AB  - Like other complex, multifaceted interventions in medicine, meditation represents
      a mixture of specific and not-so-specific elements of therapy. However,
      meditation is somewhat unique in that it is difficult to standardize, quantify,
      and authenticate for a given sample of research subjects. Thus, it is often
      challenging to discern its specific effects in order to satisfy the scientific
      method of causal inferences that underlies evidence-based medicine. Therefore, it
      is important to consider the key methodological challenges that affect both the
      design and analysis of meditation research. The goal of this paper is to review
      those challenges and to offer some practical solutions. Among the challenges
      discussed are the mismatches between questions and designs, the variability in
      meditation types, problems associated with meditation implementation, individual
      differences across meditators, and the impossibility of double-blind, placebo
      controlled meditation studies. Among the design solutions offered are aptitude x
      treatment interaction (ATI) research, mixed quantitative-qualitative methods, and
      practical (pragmatic) clinical trials. Similar issues and solutions can be
      applied more generally to the entire domain of mind-body therapies.

PMID- 15973856
TI  - Entering our broken hearts: guided imagery for posttraumatic stress--an interview
      with Belleruth Naparstek. Interview by Sheldon Lewis.

PMID- 15973857
TI  - New report calls for comprehensive, evidence-based CAM.

PMID- 15973858
TI  - Masters in disability litigation & amended Rule 53.

PMID- 15973859
TI  - What's new in palliative care for patients with heart failure?

PMID- 15973860
TI  - Metabolic syndrome.
AB  - Cardiovascular disease (CVD) and diabetes are growing public health burdens and
      remain one of the leading causes of morbidity and mortality in Canada (Heart and
      Stroke Foundation, 2003). It has become increasingly evident that individuals who
      present with a cluster of metabolic disorders, known as the metabolic syndrome,
      are at an increased risk of developing both CVD and type 2 diabetes (Ng, 2003).
      Due to the increased risk of morbidity and mortality associated with the
      metabolic syndrome, it is imperative for health care professionals to become
      familiar with the diagnostic criteria for this disorder. This will enable nurses
      to provide the appropriate primary and secondary prevention strategies in order
      to help reduce individual risk. With the help of a case study, this article will
      define metabolic syndrome, review its prevalence and risk factors, and discuss
      therapeutic interventions for this disorder.

PMID- 15973861
TI  - Ethnocultural affiliation, gender, and cardiovascular disease risk management.
AB  - Cardiovascular disease (CVD) is a major cause of morbidity and mortality in North
      America. Making behavioural changes following a diagnosis of CVD can attenuate
      the disease risk. Canada's population is composed of a growing mosaic of persons
      of various ethnic backgrounds. A person's ethnocultural affiliation and gender
      can influence the context, process and outcome of their decision-making about
      health related behaviours. Though several models exist to assist clinicians
      working with persons facing behavioural change, these models do not include
      ethnocultural affiliation and gender as fundamental components. The authors
      contend that ethnocultural affiliation and gender need to be central constructs
      in new investigations related to behavioural change and that decision-modeling
      methodology is a useful mechanism to do so.

PMID- 15973862
TI  - Palliative trajectory markers for end-stage heart failure. Or "oh Toto. This
      doesn't look like kancerous!".
AB  - Heart failure is a complex syndrome with a high morbidity and mortality rate. The
      Canadian mortality rate is between 25% and 40% annually. End-stage heart failure
      patients suffer from many debilitating symptoms. Palliative symptom management
      and funding programs can assist many of these patients. Unfortunately,
      designating a heart failure patient as palliative with a trajectory of six months
      or less is not an easy task. This is difficult to determine due to the lack of
      tangible trajectory markers and the roller-coaster nature of the trajectory
      itself. These circumstances were the impetus for a review of the current
      literature and a clinical experience in a cardiac clinic within a major teaching
      hospital in Vancouver. The objective was to determine if clear palliative
      trajectory markers for heart failure existed and, if so, could they be used to
      produce a tool to assist health care professionals to accurately determine a
      timeline of six months or less.

PMID- 15973863
TI  - Autologous cell transplantation and a discussion of the implications for nursing
      practice.
AB  - Heart failure is a progressive disorder. An estimated 400,000 Canadians are
      diagnosed annually with heart failure, and a quarter experience severe heart
      failure that is unresponsive to medical therapy. Autologous cell transplantation
      (ACT) has been proposed as a new approach for cardiac repair, and holds enormous
      potential for the regeneration of injured myocardium cells. This paper explores
      the nursing implications of ACT. Specifically, the need for ongoing education,
      the delivery of psychosocial counseling interventions, and ongoing health
      assessments of the individual will be addressed.

PMID- 15973864
TI  - A promising FUTURE for cardiovascular nursing research.

PMID- 15973865
TI  - Managing workplace stress in a dynamic environment.
AB  - Workplace stress can be either positive or negative. While positive stress is
      desirable for a variety of reasons, negative stress is not. In fact, the latter
      can result in dysfunctional consequences for health care organizations due to
      altered behavior such as increased absenteeism, changes in work habits, and job
      burnout. Management can intervene to reverse the effects of negative stress. Some
      actions include proper job design, ongoing communication with employees, team
      building, and use of a group coordinator.

PMID- 15973866
TI  - Dealing with the "always sick" employee.
AB  - Somatoform disorders occasionally surface in employees and others who, ordinarily
      unknowingly, are reacting to the stresses in their lives. Somatization is a
      process by which individuals communicate psychological distress through physical
      symptoms, thus essentially making themselves ill. However, by learning to
      recognize the signs of possible somatic problems the manager can apply various
      strategies to decrease an employee's apparent physical problems and enhance job
      performance.

PMID- 15973867
TI  - An RBRVS approach to financial analysis in health care organizations.
AB  - Resource-based relative value scales (RBRVS) have altered the outpatient
      reimbursement system of America's health care system and established a method of
      standardization whereby the efficiency of medical practices of varying size and
      complexity can be compared using a standard (the cost conversion factor) for
      analysis. This article compares the utility of RBRVS with earlier systems of
      reimbursement and concludes with a brief speculative assertion regarding the
      emergence of the next stage of ambulatory care reimbursements through ambulatory
      payment classifications.

PMID- 15973869
TI  - Learning from the politics of a merger: when being merged is not a choice.
AB  - Organizational mergers have poor track records for success. Success usually
      refers to financial success, and little or no evaluation is planned to determine
      whether the merged partners have a good cultural fit. Therefore, the social and
      psychological costs of mergers and acquisitions are high. One factor that is part
      of every merger and acquisition is politics. Politics is both a positive and a
      negative force in organizational life. This article discusses the ways politics
      affects the process and outcome of a merger, using the reorganization of the
      campuses of a large university as an example, and presents lessons learned from
      managing around the politics of this merger.

PMID- 15973870
TI  - Talk to your staff about distance education.
AB  - Most health care professionals and managers feel the need to finish their
      undergraduate or graduate degree to maintain their present position or to advance
      to a higher one. Distance education is a convenient alternative where students
      complete their studies from home using the postal service or computer.

PMID- 15973871
TI  - The media's perspectives of health care fraud and abuse--an objective assessment.
AB  - The media make it seem that greedy health care professionals are perpetrating a
      widespread conspiracy to defraud the Medicare trust fund of billions of taxpayer
      dollars. However, the media often underreport another side to the health care
      fraud and abuse issue-the flawed, inordinately complex, and ill-equipped Medicare
      payment system itself. It is difficult to quantify the purported loss of billions
      of dollars to fraud or estimate the costs to the U.S. health care system of the
      advocated increased controls. However, this discussion serves to divert attention
      from key health care issues--the many Americans who are uninsured, underinsured,
      or lack access to care and the system's administrative complexities.

PMID- 15973872
TI  - The impact of the Balanced Budget Act of 1997 on the physical therapy profession.
AB  - The Balanced Budget Act (BBA) of 1997 was one of the most significant acts of
      legislation ever to affect the physical therapy profession. Three months after
      the BBA was implemented, a survey of over 600 physical therapists in the state of
      Florida was conducted. This article examines the immediate impact of the BBA on
      physical therapists and their ability--or their perception of their ability--to
      maintain or successfully seek full-time employment in the profession.

PMID- 15973874
TI  - A manager asks: when the boss can't see what's wrong.

PMID- 15973873
TI  - Control of overtime: a department manager's never-ending task.
AB  - Overtime is an organizational necessity that is misused or abused as often as it
      is applied appropriately. As an element of labor cost it is sometimes seen as an
      extra expense to be avoided by all means, yet there are times when overtime is
      the best response to a particular need. The determination and payment of overtime
      are dictated by provisions of the Fair Labor Standards Act (FLSA), the federal
      wage and hour legislation that governs a number of aspects of employment.
      Overtime is often taken for granted, and it can readily go out of control. It is
      the task of the department manager to maintain control of overtime, adhering to a
      budget and taking active steps to ensure that only essential overtime is approved
      and worked.

PMID- 15973875
TI  - [Surgical therapy of atrial fibrillation is on its way. But catheter ablation
      must still be seen as an experimental method].

PMID- 15973876
TI  - [The cerebral cortex can be examined with near-infrared light. NIRS--a new
      promising method for diagnosis of incipient dementia].

PMID- 15973877
TI  - [One man of five aged 50 years and over referred to a urologist is diagnosed with
      cancer. PSA analysis is important for correct prioritization of the referrals].
AB  - In 20% of the men 50 years of age and older referred to a urological specialist
      clinic, a cancer, mostly a prostate cancer, was diagnosed. No symptom mentioned
      in the referral form was correlated to the diagnosis of a cancer. S-PSA density
      did not have a better predictive value than S-PSA alone. S-PSA 3.0 microg/L as a
      borderline for prostate biopsy or not had a 99.5% negative predictive value and
      only a slightly lower specificity then 4.0 microg/L. In clinical practice, for
      patients where curative treatment is feasible, S-PSA 3.0 microg/L appears to be a
      more appropriate borderline for prostate biopsy than 4 microg/L.

PMID- 15973878
TI  - [Built-in emergency brake in the balance system. Animal experiment research shows
      that a hierarchy of mechanisms compensate after acute peripheral vestibular
      decline].
AB  - A sudden unilateral loss of peripheral vestibular input results in the onset of
      acute dizziness and imbalance associated with spontaneous nystagmus, postural
      instability and nausea. Fortunately, these symptoms ameliorate rapidly, even
      without treatment, due to central nervous plastic changes which are collectively
      termed "vestibular compensation". This concept has become a widely accepted
      research model for studying lesion-induced plasticity. Recent research has dealt
      in particular with the plasticity of the medial vestibular nuclei that mediate
      the horizontal vestibulo-ocular reflex. Studies range from a cellular level in
      vitro to a functional level in vivo. Taken together, results from such studies
      have contributed greatly to what is known of vestibular compensation today. This
      article summarises evidence for several plasticity mechanisms that drive the
      recovery of spontaneous nystagmus, one of which is dependent on an endocrine
      stress-response. In the long run, such knowledge might influence the management
      and treatment of patients with balance disorders.

PMID- 15973879
TI  - [Benefits with well-educated medical secretaries. Improved coding in the patient
      registry following a course in classification and care documentation].

PMID- 15973880
TI  - [The scent--a sense which directs human beings during their life events].

PMID- 15973881
TI  - [The baby-friendly program in Sweden and Europe. A new action program for
      promotion of breast feeding in Europe is being composed by the EU].

PMID- 15973882
TI  - [Hiding refugees do not dare contact health services].

PMID- 15973884
TI  - [Substitute HSAN's punishment concept with modern incident prevention!].

PMID- 15973883
TI  - [The discussion about the apathetic children: Splits within child and adolescent
      psychiatry must be repaired].

PMID- 15973885
TI  - [Waiting lists at child and adolescent psychiatric clinics can be taken care
      of!].

PMID- 15973886
TI  - [The lack of interest within health care for the effects of nutrients must be
      broken off].

PMID- 15973887
TI  - [Seven mentally retarded siblings: about the benefits of the PKU test].

PMID- 15973888
TI  - [Feministic initiatives, long-term sick leave and insurance medicine].

PMID- 15973889
TI  - [Apathetic individuals].

PMID- 15973890
TI  - [An expected finding that sunlight can protect against cancer].

PMID- 15973891
TI  - [Fass has reached the limit of decency!].

PMID- 15973892
TI  - [Mammography screening and the concept of over-diagnosing].

PMID- 15973897
TI  - ["I have his name on the tip of my tongue"].

PMID- 15973898
TI  - [Towards a better understanding of memory].

PMID- 15973899
TI  - [Cerebral aging].

PMID- 15973900
TI  - [Time in memory].

PMID- 15973901
TI  - [Memory consultation].

PMID- 15973902
TI  - [Memory workshops to regain confidence].

PMID- 15973903
TI  - [My memory or "how to remember the good things"].

PMID- 15973904
TI  - [Memory disorders in the elderly and daily repercussions].

PMID- 15973905
TI  - [Preventing and managing behavior disorders due to dementia in institutions].

PMID- 15973906
TI  - [Confusion syndrome, a geriatric entity not to be missed].

PMID- 15973907
TI  - [An animal sculpture workshop in psychogeriatrics].

PMID- 15973908
TI  - [Validation, a communication method for patients with dementia].

PMID- 15973909
TI  - Muscle relaxants--intocostrin.

PMID- 15973910
TI  - Iatrogenic harm and anaesthesia in Australia.

PMID- 15973911
TI  - Large multicentre trials in anaesthesia: the ANZCA Clinical Trials Group.

PMID- 15973912
TI  - Outcome-based clinical indicators for intensive care medicine.
AB  - The clinical indicator is a tool used to monitor the quality of health care. Its
      use in the Intensive Care Unit (ICU) is desirable for many reasons: the
      maintenance of minimum standards, the development of best practice and the
      delivery of cost-effective health care. The utility of clinical indicators in ICU
      is limited by the lack of universal, robust, transparent, evidence-based and risk
      adjusted measures of quality, and the difficulties in defining "quality care" and
      "good outcome". Monitoring of adverse events, system descriptors, and resource
      indicators is valuable but they have a limited relationship to the quality of
      care. ICU mortality prediction models provide a global measure of quality and,
      despite their inherent deficiencies, remain one of the most robust and useful
      clinical indicators.

PMID- 15973913
TI  - Acute pain management pharmacology for the patient with concurrent renal or
      hepatic disease.
AB  - The clinical utility of most analgesic drugs is altered in the presence of
      patients with impaired renal or hepatic function not simply because of altered
      clearance of the parent drug, but also through production and accumulation of
      toxic or therapeutically active metabolites. Some analgesic agents may also
      aggravate pre-existing renal and hepatic disease. A search was performed, taking
      in published articles and pharmaceutical data to determine available evidence for
      managing acute pain effectively and safely in these two patient groups. The
      resulting information consisted mainly of small group pharmacokinetic studies or
      case reports, which included a large variation in degree of organ dysfunction. In
      the presence of renal impairment, those drugs which exhibit the safest
      pharmacological profile are alfentanil, buprenorphine, fentanyl, ketamine,
      paracetamol (except with compound analgesics), remifentanil and sufentanil. none
      of these deliver a high active metabolite load, or suffer from significantly
      prolonged clearance. Amitriptyline, bupivacaine, clonidine, gabapentin,
      hydromorphone, levobupivacaine, lignocaine, methadone, mexiletine, morphine,
      oxycodone and tramadol have been used in the presence of renal failure, but do
      require specific precautions, usually dose reduction. Aspirin,
      dextropropoxyphene, non-steroidal anti-inflammatory drugs and pethidine, should
      not be used in the presence of chronic renal failure due to the risk of
      significant toxicity. In the presence of hepatic impairment, most drugs are
      subject to significantly impaired clearance and increased oral bioavailability,
      but are poorly studied in the clinical setting. The agent least subject to
      alteration in this context is remifentanil; however the drugs' potency has other
      inherent dangers. Other agents must only be used with caution and close patient
      monitoring. Amitriptyline, carbamazepine and valproate should be avoided as the
      risk of fulminant hepatic failure is higher in this population, and methadone is
      contraindicated in the presence of severe liver disease.

PMID- 15973914
TI  - Anaesthesia for neurosurgery in the sitting position: a practical approach.
AB  - Neurosurgery in the sitting position offers advantages for certain operations.
      However, the approach is associated with potential complications, in particular
      venous air embolism. As the venous pressure at wound level is usually negative,
      air can be entrained. This air may follow any of four pathways. Most commonly it
      passes through the right heart into the pulmonary circulation, diffuses through
      the alveolar-capillary membrane and appears in expelled gas. It may pass through
      a pulmonary-systemic shunt such as a probe patent foramen ovale (paradoxical air
      embolism); it may collect at the superior vena cava-right atrial junction. Rarely
      it may traverse through lung capillaries into the systemic circulation. Many
      monitors, such as the precordial Doppler; capnography, pulmonary artery catheter;
      transoesophageal echocardiography are useful for venous air embolism detection,
      with transoesophageal echocardiography being today's gold standard. Various
      manoeuvres, including neck compression and volume loading, are also useful in
      reducing the incidence of venous air embolism. Volume loading, in particular; is
      very helpful as it reduces the risk of hypotension. Other particular concerns to
      the anaesthetist are airway management, avoidance of pressure injuries, and the
      risk of pneumocephalus, oral trauma, and quadriplegia. Newer anaesthetic agents
      have made the choice of anaesthetic technique easier. An appreciation of the
      implications of neurosurgery in the sitting position can make the procedure safer

PMID- 15973915
TI  - Neurosurgery in the sitting position: a case series.
AB  - Prospective data was collected on 58 patients having neurosurgery in the sitting
      position in one institution. The incidence of venous air embolism was 43%
      (25/58), of which the majority were small or moderate in size. There were no
      episodes of paradoxical air embolism. The incidence of other intraoperative and
      postoperative complications was low. There was no mortality or serious morbidity.
      With a proper understanding of the pathophysiology of venous air embolism and the
      use of sensitive monitoring, anaesthesia for sitting position neurosurgery can be
      provided safely.

PMID- 15973916
TI  - Anaesthetic adverse incident reports: an Australian study of 1,231 outcomes.
AB  - While there have been previous studies looking at patterns of litigation against
      anaesthetists overseas, there is little reported on the trends in Australia. This
      study was performed to ascertain current reporting rates of anaesthetic
      incidents, and from what areas these reports arise. Over the five years spanning
      January 1999 until December 2003, 1,231 adverse anaesthetic outcomes were
      reported to United Medical Protection by Australian anaesthetists. As in other
      studies, damage relating to airway instrumentation was the most frequently
      reported, comprising 261 incidents (21.8%). Complications related to epidural
      blockade were the next most common, accounting for 182 outcomes (15.2%). Other
      common areas generating incident reports included nerve injuries, respiratory
      complications, drug side-effects and death. To date 147 claims (12.3%) have
      arisen from these incident reports. Knowledge of these areas of risk should
      translate into more effective risk management with reduction in claims and
      adverse patient outcomes.

PMID- 15973917
TI  - Can bioimpedance determine the volume of distribution of antibiotics in sepsis?
AB  - The relationship between the volume of distribution, assessed according to the
      two-compartmental pharmacokinetic model, and extracellular water estimated by
      bioimpedance was studied in mechanically ventilated patients with sepsis and
      capillary leak. A prospective observational study was performed in a twenty-bed
      general intensive care unit in the university hospital. Patients received either
      vancomycin (n = 16) or netilmicin (n = 12) for more than 48 hours. Those with
      ascites, pleural effusion, on renal replacement therapy or with haemodynamic
      instability were excluded. Serum concentrations of drugs were taken for
      pharmacokinetic analysis before, 1 hour and 4 hours after the 30 minute infusion.
      Bioimpedance measurement was performed at the time of the third sampling. The
      protocol was repeated after 24 hours. Fluid balance during the 24 hour interval
      was recorded. Extracellular water was increased and represented 45.6 to 46.6% of
      total body water Fluid balance correlated with the change of extracellular water
      (r = 0.82, P < 0.0001) and total body water (r = 0.74, P < 0.0001). Volumes of
      distribution of vancomycin (0.677 +/- 0.339 l/kg) and netilmicin (0.505 +/- 0.172
      l/kg) were increased compared to normal values. A correlation was demonstrated
      between volume of distribution (Vd(area)) of vancomycin and extra cellular
      water/total body ratio (r = 0.70, P < 0.0001). The central compartment
      distribution volume (V1) of netilmicin correlated with extracellular water/total
      body water ratio (r = 0.60, P < 0.003). Serum concentrations above the
      recommended therapeutic range were detected in 81.2% of patients on vancomycin
      and in 50% of patients on netilmicin. Increased volumes of distribution can be
      estimated by the bioimpedance measurements but are not associated with
      requirements for higher dosage of the glycopeptide or aminoglycoside antibiotics.

PMID- 15973918
TI  - Comparative study between propofol in a long-chain triglyceride and propofol in a
      medium/long-chain triglyceride during sedation with target-controlled infusion.
AB  - This study was performed to compare the pharmacological characteristics of
      propofol in an emulsion of both medium- and long-chain triglycerides (MCT/LCT)
      with those of propofol in an LCT emulsion, by measuring the sedative level and
      the plasma concentration of propofol during sedation using a target-controlled
      infusion (TCI) technique. Forty ASA 1 or 2 adult patients who required spinal
      anaesthesia for surgery were enrolled in this study. The patients were divided
      into two groups: a propofol LCT group (n = 20) and a propofol MCT/LCT group (n =
      20). Propofol was injected intravenously at target blood concentrations of 2.0,
      3.0 and 4.0 microg x ml(-1). The bispectral (BIS) index was recorded, and
      arterial blood was drawn to measure the actual plasma concentrations of propofol
      at each predicted concentration. Propofol was assayed by high-performance liquid
      chromatography. Propofol MCT/LCT was associated with significantly less pain than
      propofol LCT (P < 0.05). There were no significant differences between the two
      groups in BIS index or in plasma concentration of propofol at each predicted
      concentration. Computer-generated TCI of propofol MCT/LCT during sedation is
      comparable with that of propofol LCT with respect to pharmacokinetics and
      pharmacodynamics. The formulation of MCT/LCT has a beneficial effect with respect
      to less pain on injection.

PMID- 15973919
TI  - Effect of newer anaesthetics on duration of stay in postanaesthesia care unit in
      patients undergoing major abdominal surgery.
AB  - Newer anaesthetic agents, such as remifentanil and sevoflurane, are more
      expensive than conventional anaesthetics, such as isoflurane and fentanyl.
      However, newer anaesthetics might outweigh their higher acquisition costs by
      reducing length of stay in the postanaesthesia care unit and thereby reducing
      personnel costs. We retrospectively investigated the influence of newer
      anaesthetics on time to eligibility for discharge from the postanaesthesia care
      unit in consecutive patients undergoing major abdominal surgery. Using a chart
      review, patients undergoing major abdominal surgery with three different
      anaesthetic regimens (isoflurane/fentanyl (n = 80), sevofluranelfentanyl (n =
      40), and sevoflurane/remifentanil (n = 42)) were compared regarding duration of
      anaesthesia, surgery, time till extubation, and time to eligibility for discharge
      from the postanaesthesia care unit. Extubation times were shorter in patients in
      the sevoflurane/fentanyl and the sevoflurane/remifentanil groups compared to
      patients in the isoflurane/fentanyl group. Time to eligibility to discharge from
      the postanaesthesia care unit was similar in isoflurane/fentanyl and
      sevoflurane/fentanyl group. In the sevoflurane/fentanyl group, time to
      eligibility for discharge from the unit showed a tendency to be increased (P =
      0.08), however these patients were significantly older compared to the other
      groups. Sevoflurane and remifentanil did not appear to reduce time to eligibility
      to discharge from the postanaesthesia care unit in our patients undergoing major
      abdominal surgery compared to isoflurane and fentanyl. This study highlighted the
      necessity for carefully planned transition from remifentanil to other longer
      acting analgesia in our patients.

PMID- 15973920
TI  - Control of imported and acquired methicillin-resistant Staphylococcus aureus
      (MRSA) in mechanically ventilated patients: a dose-response study of enteral
      vancomycin to reduce absolute carriage and infection.
AB  - This study aimed to quantify the animate source provided by the patients using
      the concept of "absolute carriage" by multiplying the carrier rate by the level
      of carriage; and to compare the impact of a low and high dose of an oropharyngeal
      vancomycin gel on the absolute MRSA carriage and infection. In all, 265 patients
      were included, 126 were MRSA positive. Fifty-five patients received 2% vancomycin
      gel during the first year whilst 4% vancomycin gel was given to 50 patients
      during the second year. Surveillance swabs of throat and rectum were obtained
      from all eligible patients on admission and then twice weekly. The vancomycin
      protocol was started as soon as the surveillance cultures were positive for MRSA.
      Those patients received one gram of enteral vancomycin daily, divided into four
      doses. During the first year 2% vancomycin gel 4 ml (80 mg) was applied in the
      oropharynx in four doses in addition to the enteral solution (Group A). During
      the second year 4% vancomycin gel 4 ml (160 mg) was used (Group B). The absolute
      carriage was high during both periods: 3.6 for Group A, and 3.2 for Group B. The
      4% vancomycin protocol significantly reduced the absolute carriage, compared to
      the 2% vancomycin protocol: 2.6 versus 1.5 (P < 0.01). Significant reduction in
      secondary endogenous infections was found in the second year: seven versus 15
      patients (P < 0.05). A total of 3,588 microbiological samples were processed.
      Neither Staphylococcus aureus with intermediate sensitivity to vancomycin (VISA)
      nor vancomycin-resistant enterococci (VRE) were detected.

PMID- 15973922
TI  - Assessment of internal diameter and cross-sectional area of right internal
      jugular vein pre-induction and post-intubation.
AB  - This prospective observational study compared the internal diameter and cross
      sectional area of the right internal jugular vein pre-induction and post
      initiation of positive pressure ventilation. Twenty patients undergoing coronary
      artery bypass surgery were studied. Measurements were taken with the operating
      table tipped to 30 degrees head down and the head turned 10 degrees away from the
      side of cannulation. There was a statistically significant increase in both
      measurements post-intubation. This study suggests that it may be easier and safer
      to perform cannulation of RIJV after institution of intermittent positive
      pressure ventilation in patients in the modified Trendelenburg position.

PMID- 15973921
TI  - Differential anaesthetic effects following microinjection of thiopentone and
      propofol into the pons of adult rats: a pilot study.
AB  - Identifying the central nervous system sites of action of anaesthetics is
      important for understanding the link between their molecular actions and clinical
      effects. The aim of the present pilot study was to compare the anaesthetic effect
      of bilateral microinjections of propofol and thiopentone (both 200 microg/microl,
      in Intralipid and 0.9% saline respectively) into a recently discovered
      anaesthetic-sensitive region in the rat brainstem, the "mesopontine tegmental
      anaesthetic area" (MPTA). Microinjections (1 microl per side) were made into the
      MPTA of fifteen male Sprague-Dawley rats. The effect of each agent on spontaneous
      behaviour, postural control and nociceptive responsiveness was subjectively
      assessed according to established criteria. The main finding was that thiopentone
      induced an "anaesthesia-like" state, including complete atonia and loss of
      righting ability, in 20% of the subjects. Overall, thiopentone significantly
      reduced postural control and had a moderate antinociceptive effect compared to
      saline microinjections (P < 0.01 and 0.05, respectively, Wilcoxon test). In
      contrast, propofol did not induce "anaesthesia" in any animal tested, although a
      similar antinociceptive effect to that of thiopentone was observed (P < 0.05,
      Wilcoxon test). In summary, propofol and thiopentone have different effects when
      microinjected into the MPTA. While both agents reduced reflex withdrawal to a
      nociceptive stimulus, only thiopentone induced an "anaesthesia-like" state.

PMID- 15973923
TI  - Intra- and extra-pericardial lengths of the superior vena cava in vivo:
      implication for the positioning of central venous catheters.
AB  - To reduce the possibility of cardiac tamponade, a rare but lethal complication of
      central venous catheters, the tip of the central venous catheter should be
      located above the cephalic limit of the pericardial reflection, not only above
      the superior vena cava-right atrium junction. This study was performed to measure
      the superior vena cava lengths above and below the pericardial reflection in
      cardiac surgical patients. Cardiac surgical patients (n = 61; 27 male), whose age
      [mean +/- SD (range)] was 47 +/- 15 (15-75) years, were studied. The
      intrapericardial and extrapericardial lengths, and the length of the medial
      duplicated part were measured separately. The whole vertical lengths of the
      superior vena cava on either side were calculated respectively by adding the
      intra-and extrapericardial and medial duplication lengths. The lateral
      extrapericardial was 29.1 +/- 6.5 (Mean +/- SD) (9-49) mm (range), and lateral
      extrapericardial length was 32.6 +/- 6.9 (20-53) mm. The medial extrapericardial
      length was 23.3 +/- 5.0 (11-39) mm, medical duplicated length was 7.2 +/- 3.3 (4
      20) mm, and medial intrapericardial was 28.3 +/- 7.0 (20-52) mm. The averaged
      superior vena cava length of both sides was 60.3 +/- 9.0 (44.5-90) mm. Almost
      half of the superior vena cava was found to be within the pericardium and half
      out. This information may be helpful in deciding how far a central venous
      catheter should be withdrawn beyond the superior vena cava-right atrial junction
      during right atrial electrocardiographic guided insertion, and in the prediction
      of optimal central venous catheter insertion depth.

PMID- 15973924
TI  - Heparin-induced thrombocytopenia and the use of r-hirudin during cardiopulmonary
      bypass.
AB  - We report the successful use of r-hirudin (lepirudin) for cardiopulmonary bypass
      in a 67-year-old man who developed heparin-induced thrombocytopenia type II
      during heparin treatment of an extensive deep venous thrombosis. Lepirudin was
      monitored by the modified ecarin clotting time in a "mobile laboratory" set up
      next to the cardiac theatre, aiming for lepirudin levels of 3.5 to 4.5 microg/ml
      during bypass.

PMID- 15973925
TI  - Severe hypotension and hepatic dysfunction in a patient undergoing scoliosis
      surgery in the prone position.
AB  - Many patients with neuromuscular disorders develop progressive scoliosis and
      require corrective surgery. We present a patient with hereditary motor and
      sensory neuropathies who developed severe hypotension during corrective surgery
      for thoracolumbar scoliosis. The haemodynamic disturbance was probably secondary
      to thoracic hyperlordosis and the knee-chest position and was aggravated by
      surgical manipulation. This may be prevented by tailored preoperative evaluation
      of different patient prone position supports and frames in order to select that
      which causes least cardiovascular and respiratory disturbance. This patient also
      developed severely deranged liver function postoperatively and the possible
      aetiology is discussed.

PMID- 15973926
TI  - Severe transfusion-related acute lung injury in the intensive care unit secondary
      to transfusion of fresh frozen plasma.
AB  - Transfusion-related acute lung injury (TRALI) is a life-threatening complication
      of transfusion of blood products. A case of severe TRALI secondary to infusion of
      fresh frozen plasma in the intensive care unit is discussed. Additionally, the
      aetiology and pathogenesis of this relatively under-diagnosed and under-reported
      clinical entity is reviewed. It is our conclusion that proper diagnosis and
      reporting is necessary for prompt and appropriate treatment of the patient and to
      prevent additional reactions in other patients.

PMID- 15973927
TI  - Cardiac herniation following pneumonectomy--an old complication revisited.
AB  - Cardiac herniation is a recognised complication of pneumonectomy when a
      pericardial defect has been made during resection. This complication is very rare
      and, with the increasing preference for more limited resections, is even less
      frequently encountered now than it was several decades ago. Uncorrected cardiac
      herniation is usually lethal, with a high incidence of morbidity and mortality
      even after correction. We present a case of left-sided cardiac herniation
      following intrapericardial pneumonectomy to illustrate the difficulty of making
      this rare diagnosis. Aetiology, pathophysiology, clinical picture and diagnosis
      of cardiac herniation are reviewed. We also describe the treatment and prevention
      of this serious complication. Cardiac herniation should be considered in any
      patient with acute deterioration after pneumonectomy.

PMID- 15973928
TI  - Total knee replacement in a patient taking clopidogrel.

PMID- 15973929
TI  - Comparison of disposable and reusable laryngeal mask airways in spontaneously
      ventilating adult patients.

PMID- 15973930
TI  - An evaluation of the relative efficacy of an open airway, an oxygen reservoir and
      continous positive airway pressure 5 cmH2O on the non-ventilated lung.

PMID- 15973931
TI  - Design of new anaesthesia machines.

PMID- 15973932
TI  - Acute head and neck oedema and central venous occlusion.

PMID- 15973933
TI  - Misdiagnosed foreign body aspiration resulting in cardio-pulmonary arrest and
      multi-organ failure.

PMID- 15973934
TI  - A "regurgitating" laryngeal mask airway for scenario training.

PMID- 15973935
TI  - A vulnerable adults act is long overdue.

PMID- 15973936
TI  - Improving patient nutrition.

PMID- 15973937
TI  - How I coped with...a hurricane.

PMID- 15973939
TI  - What you need to know about porphyria.

PMID- 15973938
TI  - The role of nurses in blood services and donor sessions.
AB  - On 14 June the National Blood Service (NBS) is hosting World Blood Donor Day
      (WBDD). The need for blood is universal and many people know of someone who has
      required blood to save or improve her or his life. The nurse is clinically
      responsible for the donation session, with the care of donors and the safety of
      the blood being their main priority.

PMID- 15973940
TI  - Hepatitis A vaccination.

PMID- 15973941
TI  - Guidelines on use of restraint in neuroscience settings.
AB  - Nurses working in neuroscience often have to manage patients whose behaviour puts
      themselves or others at risk of injury or compromises their care and treatment.
      The National Benchmarking Group has explored issues related to the restraint of
      patients and made some key recommendations. The aim was to develop guidelines for
      staff working in specialist areas on how to manage challenging behaviour while
      maintaining patient safety and dignity.

PMID- 15973942
TI  - Improving practice through a system of clinical supervision.
AB  - Although a familiar concept, clinical supervision has yet to be available to all
      nurses. This is often due to difficulties in implementation. Having recognised
      these problems, one acute paediatric ward introduced the role of clinical
      supervision facilitator. This enabled the introduction of a system of clinical
      supervision and ensured a sustained change in practice.

PMID- 15973943
TI  - The nurse role in managing and treating sleep disorders.
AB  - Obstructive sleep apnoea/hypopnoea syndrome affects a significant number of
      middle-aged people. By causing the person with the condition to wake repeatedly
      during the night in order to restart breathing, it causes excessive daytime
      sleepiness and impairs cognitive function and driving ability. It can also
      adversely affect family relationships, particularly with partners whose sleep may
      also be disturbed. Nurses have a role in the diagnosis and management of the
      condition through appropriate questioning, observation, advice on lifestyle
      choices, and support for treatment. The article also focuses on narcolepsy.

PMID- 15973944
TI  - New ways to work in mental health.

PMID- 15973945
TI  - Value in dentistry.

PMID- 15973946
TI  - Optimum surface properties of oxidized implants for reinforcement of
      osseointegration: surface chemistry, oxide thickness, porosity, roughness, and
      crystal structure.
AB  - PURPOSE: To investigate detailed surface characterization of oxidized implants in
      a newly invented electrolyte system and to determine optimal surface oxide
      properties to enhance the bone response in rabbits. MATERIALS AND METHODS: A
      total of 100 screw-type titanium implants were prepared and divided into 1
      control group (machine-turned implants) and 4 test groups (magnesium ion
      incorporated oxidized implants). Forty implants were used for surface analyses. A
      total of 60 implants, 12 implants from each group, were placed in the tibiae of
      10 New Zealand white rabbits and measured with a removal torque test after a
      healing period of 6 weeks. RESULTS: For the test groups, the oxide thicknesses
      ranged from about 1,000 to 5,800 nm; for the control group, mean oxide thickness
      was about 17 nm. The surface morphology showed porous structures for test groups
      and nonporous barrier film for the control group. Pore diameter ranged from < or
      = 0.5 microm to < or = 3.0 microm. In regard to surface roughness, arithmetic
      average height deviation (Sa) values varied from 0.68 to 0.98 microm for test
      implants and 0.55 microm for control implants; developed surface ratio (Sdr)
      values ranged from 10.6% to 46% for the test groups and were about 10.6% for the
      control group. A mixture of anatase and rutile-type crystals were observed in the
      test groups; amorphous-type crystals were observed in the control group. After a
      healing period of 6 weeks, removal torque measurements in all 4 test groups
      demonstrated significantly greater implant integration as compared to machine
      turned control implants (P < or = .033). DISCUSSION: Determinant oxide properties
      of oxidized implants are discussed in association with bone responses. Of all
      surface properties, RTVs were linearly increased as relative atomic
      concentrations of magnesium ion increase. CONCLUSIONS: Surface properties of the
      oxidized implants in the present study, especially surface chemistry, influenced
      bone responses. The surface chemistry of the optimal oxidized implant should be
      composed of approximately 9% magnesium at relative atomic concentration in
      titanium oxide matrix and have an oxide thickness of approximately 1,000 to 5,000
      nm, a porosity of about 24%, and a surface roughness of about 0.8 microm in Sa
      and 27% to 46% in Sdr; its oxide crystal structure should be a mixture of anatase
      and rutile-phase crystals.

PMID- 15973947
TI  - Immediate and early loading of SLA ITI single-tooth implants: an in vivo study.
AB  - PURPOSE: The purpose of this investigation was to determine whether early and
      immediate loading of dental implants resulted in adverse consequences as
      determined clinically, radiographically, and histologically. MATERIALS AND
      METHODS: In a canine model, 48 sand-blasted, large-grit, acid-etched (SLA)
      surfaced implants were placed at 4 different times before definitive restoration
      and loading. These times were 3 months (group A), 21 days (group B), 10 days
      (group C), and 2 days (immediately) (group D) before loading. Each implant was
      restored at the same time with a single gold screw-retained crown. Immediately
      after restoration all crowns were placed in function. Standardized periapical
      radiographs were made 1, 2, and 3 months after restoration. At the end of the
      study, block sections were obtained for histologic examination. Changes in
      crestal bone height on the mesial and distal aspects of each implant and the
      change in bone density of the coronal 3 mm of crestal bone were recorded.
      Primary, secondary, and total bone-to-implant contact; bone marrow-to-implant
      contact; and connective tissue-to-implant contact were evaluated histologically.
      RESULTS: All implants were osseointegrated at the end of the study; no clinical
      failures of integration were noted. The changes in crestal bone heights for
      groups A, B, C, and D (means +/- SE) were 0.02 +/- 0.07 mm, 0.30 +/- 0.08 mm,
      0.15 +/- 0.08 mm, and 0.35 +/- 0.18 mm, respectively. Total bone-to-implant
      contact for the 4 groups was 69.1%, 71.3%, 74.6%, and 75.2%, respectively (P >
      .57). DISCUSSION: Under the conditions of this study no statistically significant
      differences were noted between the 4 different loading protocols for any of the
      parameters recorded. This finding is consistent with other recent studies and
      case reports. CONCLUSION: The findings of this study indicate that early and
      immediate loading of single-unit SLA surfaced implants was possible in this
      model. (More than 50 references.)

PMID- 15973948
TI  - A prospective multicenter randomized clinical trial of autogenous bone versus
      beta-tricalcium phosphate graft alone for bilateral sinus elevation: histologic
      and histomorphometric evaluation.
AB  - PURPOSE: Two different graft materials, beta-tricalcium phosphate (Cerasorb) and
      autogenous bone, were used in the same patient. The objective was to determine
      whether donor site morbidity could be avoided by using pure-phase beta-tricalcium
      phosphate (Cerasorb). MATERIALS AND METHODS: Bilateral sinus grafting was
      performed on 20 selected patients; Cerasorb was used on the experimental side,
      and autogenous bone was used on the control side. In each patient, one side was
      randomly designated the experimental side. In 10 of the 20 patients, the maxilla
      reconstruction included sinus grafting and onlay bone grafting. Implants were
      placed 6 months after the procedure. In addition to routine panoramic
      radiographs, in 10 of the 20 patients, 2- and 3-dimensional computerized
      tomographic examinations were performed pre- and postoperatively and after
      implantation. Eighty bone biopsy specimens were taken at the time of implant
      placement. RESULTS: Histologically and histomorphometrically, there was no
      significant difference between the experimental and control grafts in terms of
      the quantity and rate of ossification. For each histologic sample, the total
      surface area, the surface area that consisted of bone, and the surface area that
      consisted of graft material were measured in mm2, and bone and graft material
      were analyzed as percentages of the total. The mean percentage bone areas were
      36.47% +/- 6.9% and 38.34% +/- 7.4%, respectively; the difference was not
      significant (P = .25). DISCUSSION AND CONCLUSION: Comparisons with other studies
      reveal that beta-tricalcium phosphate (Cerasorb) is a satisfactory graft
      material, even without autogenous bone.

PMID- 15973949
TI  - Accuracy assessment of image-guided implant surgery: an experimental study.
AB  - PURPOSE: To accurately accomplish the drilling of an implant socket, the use of
      image-guided navigation has become an option. The aim of this study was to
      evaluate the 3-dimensional (3D) accuracy of navigation-guided drilled holes.
      MATERIALS AND METHODS: Laboratory accuracy measurements were obtained on an
      acrylic resin model with standardized target holes drilled by a computerized
      numerical control machine. The model was scanned by a multislice computerized
      tomography scanner and registered with fiducial marker-based algorithms.
      Navigated drillings were performed using an optical navigation system based on
      passive marker technology. Coordinates of drilled holes were determined by a 3D
      digitizer probe, and accuracy was assessed for all 5 degrees of freedom using a
      computer-aided design system (Pro/Engineer). RESULTS: A total of 240 drillings
      were evaluated. Mean registration error was 0.86 mm (SD 0.25 mm). Target point
      deviation between preplanned and actual drill starting point was 0.95 mm (SD 0.25
      mm). The deviation in terms of full length was 0.97 mm (SD 0.34 mm), and mean
      angular deviation on the coronal and sagittal planes was 1.35 degrees (SD 0.42
      degrees). DISCUSSION: The accuracy of image-guided navigation depends on imaging
      modalities, patient-to-image registration procedures, and instrument tracking.
      The technical accuracy and the navigation procedure, as evaluated in the study
      presented, seem to be of minor influence. CONCLUSION: The data obtained by this
      in vitro study demonstrate that the accuracy of navigation-based drilling may be
      sufficient for clinical practice, particularly in terms of the transferability of
      preplanned trajectories. However, in vivo clinical trials need to be performed to
      evaluate the clinical accuracy and treatment quality of navigation-guided
      interventions.

PMID- 15973950
TI  - A histomorphometric evaluation of factors influencing the healing of bony defects
      surrounding implants.
AB  - PURPOSE: The authors' aim was to perform a histomorphometric study of the healing
      of bone defects created adjacent to titanium and hydroxyapatite (HA) -coated
      implants and covered with either a resorbable or a nonresorbable membrane in
      combination with different filler materials and to evaluate to what degree
      coating, membrane, and/or filler influenced the healing of the defects. MATERIALS
      AND METHODS: Posterior teeth were extracted from the mandibles of 10 baboons, and
      12 implants were placed in each animal in the edentulous areas. The implants were
      either titanium or HA-coated, the membranes were either Vicryl, Gore-Tex, or
      Resolut, and the filler was either demineralized freeze-dried bone (DFDB),
      autogenous bone, or Biocoral. The implants were observed for either 3, 6, 9, 12,
      or 18 months. The volume of newly generated tissue and the relative contribution
      of bone, marrow, and filler were evaluated, as was relative extension of
      resorption, formation, and quiescent surface. RESULTS: The results indicated that
      autogenous bone is still the gold standard, but both the DFDB and Biocoral
      compared favorably to it. Both filler materials were being gradually replaced by
      bone; this process was not yet finished at 18 months postsurgery. DISCUSSION:
      Since even the sterilization of DFDB cannot exclude the possibility of a disease
      transmission, it is important to find an appropriate substitute. Both filler and
      membranes contributed to the re-establishment of the original volume; better
      results were achieved with the Vicryl and Gore-Tex membranes than with the
      Resolut. Biocoral can be considered an effective material. CONCLUSION: A bony
      defect is not necessarily a contraindication for the placement of an implant.
      (More than 50 references.)

PMID- 15973951
TI  - Immediately loaded implants supporting fixed prostheses in the edentulous
      maxilla: a preliminary clinical and radiologic report.
AB  - PURPOSE: To evaluate the survival rate of immediately loaded ITI sand-blasted,
      large-grit, acid-etched (SLA) solid-screw dental implants in the edentulous
      maxilla after 8 months of loading. MATERIALS AND METHODS: Twenty-eight patients
      (mean age 63 years) with edentulous maxillae each received 6 implants and 1
      implant-supported fixed provisional prosthesis within 24 hours after surgery.
      After a mean healing time of 15 weeks, the patient received a definitive, screw
      retained, implant-supported fixed prosthesis. A total of 168 implants were
      placed. Clinical parameters were registered after 1 month of loading with the
      implant-supported fixed prostheses as well as 8 months after implant placement.
      Radiologic examinations and assessments were made at implant placement and after
      8 months. RESULTS: The mean marginal bone level at implant placement was 1.6 mm
      (range 0 to 5.1; SD 1.1) apical of the reference point (the implant shoulder).
      The mean marginal bone level at the 8-month follow-up was 3.2 mm (range 0.4 to
      5.9; SD 1.1) apical of the reference point. Three implants failed during the
      healing period. DISCUSSION: The improved results in the present study might be a
      result of the positive effect of splinting the implants immediately after
      placement. CONCLUSION: ITI SLA solid-screw implants immediately loaded (ie,
      loaded within 24 hours of placement) and supporting fixed prostheses had
      successful survival rates after 8 months. The present results constitute a solid
      baseline for future follow-up studies.

PMID- 15973952
TI  - Comparison of dental implant systems: quality of clinical evidence and prediction
      of 5-year survival.
AB  - PURPOSE: This literature review was conducted to evaluate the quality of current
      evidence of clinical performance provided by American Dental Association
      certified dental implant manufacturers and manufacturers with strong market
      penetration in the United States. The study also compared the clinical
      performance of different dental implant systems. MATERIALS AND METHODS: A letter
      was sent to 6 implant manufacturers requesting 10 references each that validated
      the manufacturer's implant system in a variety of clinical applications.
      References were reviewed and classified relative to strength of evidence. Data
      extraction was then performed. Comparisons of implant survival data from 5-year
      studies were made, and data were pooled to establish an overall 5-year survival
      rate with confidence intervals (CIs). RESULTS: A total of 69 references were
      provided by the 6 implant manufacturers (Astra Tech, Centerpulse,
      Dentsply/Friadent, Implant Innovations, Nobel Biocare, and Straumann) but only 59
      articles were available for review. Of those references, most were level-4 (case
      series) or level-5 (expert opinion) articles. Five-year survival data were
      extracted from 17 articles demonstrating overlap of CIs from the weighted average
      of the pooled data from each specific manufacturer; substantial equivalence of
      all implant systems was demonstrated based upon survival alone at 5 years. When
      all data were pooled, the 5-year survival rate of 96% (CI: 93% to 98%) was
      observed for a total of 7,398 implants. DISCUSSION: No obvious differences in
      implant survival were observed when comparing implant systems. CONCLUSIONS: The
      evidence supporting implant therapy is generally derived from level-4 case series
      rather than higher-level cohort or controlled clinical trials. Articles that
      directly compared different implant systems were not found. Five-year implant
      survival rates easily exceeded the minimums recommended by the American Dental
      Association certification program. (More than 50 references.)

PMID- 15973953
TI  - Bone density assessments of dental implant sites: 2. Quantitative cone-beam
      computerized tomography.
AB  - PURPOSE: Bone density was evaluated in designated implant sites using a novel
      volumetric computerized tomographic device. Those measurements were then compared
      with traditional quantitative computerized axial tomography and subjective bone
      density evaluation. MATERIALS AND METHODS: Sixty-three potential sites for
      implant placement in jaws from 9 human cadavers were used. Indicator rods 2 mm in
      diameter were placed in all sites. Radiographic images representing 1-mm
      buccolingual slices immediately mesial and distal to the rods were selected. Bone
      density in Hounsfield units was assessed using quantitative cone-beam
      computerized tomography (QCBCT) and quantitative computerized tomography (QCT) in
      a standardized implant area superimposed on the images. Bone density was also
      subjectively evaluated by 2 independent examiners using the Lekholm and Zarb
      classification. RESULTS: The QCBCT bone density values were generally found to be
      higher than the corresponding QCT measurements. The correlations between the QCT
      and QCBCT values, however, were very high in spite of this systematic difference
      between the 2 methods. The Lekholm and Zarb ratings for the 2 examiners showed
      correlation coefficients ranging between 0.46 and 0.60 for the relationships with
      the QCBCT values. For each of the scores used for the subjective classification,
      however, a wide range of corresponding QCBCT values was observed. DISCUSSION:
      High dosage has been the major impediment to the utilization of CT in implant
      dentistry. The development of a reliable volumetric CT alternative with reduced
      radiation should provide an effective method for the assessment of both bone
      quantity and bone density. CONCLUSIONS: Access to objective radiographic bone
      density values should constitute a valuable supplement to subjective bone density
      evaluations prior to implant placement. QCBCT could be considered an alternative
      diagnostic tool for preoperative bone density evaluation, especially since the
      reported radiation dose is minimal.

PMID- 15973954
TI  - Early wound healing around endosseous implants: a review of the literature.
AB  - The knowledge base of information related to early wound healing around
      endosseous dental implants is rapidly changing and expanding. Unless one is
      directly involved with creating this pool of information or has an extraordinary
      interest in the literature of the field, it is difficult to keep up to date with
      the flow of information. This article is intended to provide the clinician with a
      state-of-the-art review of the current literature related to early wound healing
      and the creation of an osseointegrated interface between living and nonliving
      structures. While some literature dealing with basic laboratory studies including
      tissue culture is discussed, the primary focus of the article is the in vivo
      literature, ie, animal and human studies.

PMID- 15973956
TI  - Zygomatic bone: anatomic bases for osseointegrated implant anchorage.
AB  - PURPOSE: The aim of the present study was to evaluate zygomatic bone thickness
      considering a possible relationship between this parameter and cephalic index
      (CI) for better use of CI in the implant placement technique. MATERIALS AND
      METHODS: CI was calculated for 60 dry Brazilian skulls. The zygomatic bones of
      the skulls were divided into 13 standardized sections for measurement. Bilateral
      measurements of zygomatic bone thickness were made on dry skulls. RESULTS:
      Sections 5, 6, 8, and 9 were appropriate for implant anchorage in terms of
      location. The mean thicknesses of these sections were 6.05 mm for section 5, 3.15
      mm for section 6, 6.13 mm for section 8, and 4.75 mm for section 9. In only 1
      section, section 8, did mean thickness on 1 side of of the skull differ
      significantly from mean thickness on the other side (P <.001). DISCUSSION: For
      the relationship between quadrant thickness and CI, sections 6 and 8 varied
      independently of CI. Section 5 associated with brachycephaly, and section 9
      associated with subbrachycephaly, presented variations in the corresponding
      thickness. CONCLUSION: Based on the results, implants should be placed in
      sections 5 and 8, since they presented the greatest thickness, except in
      brachycephalic subjects, where thickness was greatest in section 5, and in
      subbrachycephalic subjects, where thickness was greatest in section 9. CI did not
      prove to be an appropriate parameter for evaluating zygomatic bone thickness for
      this sampling. (More than 50 references.)

PMID- 15973955
TI  - Maxillary sinus floor augmentation using a beta-tricalcium phosphate (Cerasorb)
      alone compared to autogenous bone grafts.
AB  - PURPOSE: A prospective human clinical study was conducted to determine the
      clinical and histologic bone formation ability of 2 graft materials, a beta
      tricalcium phosphate (Cerasorb; Curasan, Kleinostheim, Germany) and autogenous
      chin bone, in maxillary sinus floor elevation surgery. MATERIALS AND METHODS: Ten
      healthy patients underwent a bilateral (n = 6) or unilateral (n = 4) maxillary
      sinus floor elevation procedure under local anesthesia. In each case, residual
      posterior maxillary bone height was between 4 and 8 mm. In cases of bilateral
      sinus floor elevation, the original bone was augmented with a split-mouth design
      with 100% beta-tricalcium phosphate on the test side and 100% chin bone on the
      contralateral control side. The unilateral cases were augmented with 100% beta
      tricalcium phosphate. After a healing period of 6 months, ITI full body screw
      type implants (Straumann, Waldenburg, Switzerland) were placed. At the time of
      implant surgery, biopsy samples were removed with a 3.5-mm trephine drill.
      RESULTS: Sixteen sinus floor elevations were performed. Forty-one implants were
      placed, 26 on the test side and 15 on the control side. The clinical
      characteristics at the time of implantation differed, especially regarding
      clinical appearance and drilling resistance. The increase in height was examined
      radiographically prior to implantation and was found to be sufficient in all
      cases. After a mean of nearly 1 year of follow-up, no implant losses or failures
      had occurred. DISCUSSION: The promising clinical results of the present study and
      the lack of implant failures are probably mainly the result of requiring an
      original bone height of at least 4 mm at the implant location. CONCLUSION:
      Although autogenous bone grafting is still the gold standard, according to the
      clinical results, the preimplantation sinus floor elevation procedure used, which
      involved a limited volume of beta-tricalcium phosphate, appeared to be a
      clinically reliable procedure in this patient population.

PMID- 15973957
TI  - Preliminary data of a prospective clinical study on the Osseotite NT implant: 18
      month follow-up.
AB  - PURPOSE: This article provides preliminary clinical results on the Osseotite NT
      implant, which was developed to simplify surgical procedure and cover an extended
      range of indications. Placement characteristics of NT and standard Osseotite
      implants were also compared in an in vitro study. MATERIALS AND METHODS: The in
      vitro placement characteristics of NT and standard Osseotite implants of 4.0 mm
      diameter and 8.5 to 15 mm in length were compared. In addition, a total of 182 NT
      implants (96 maxillary and 86 mandibular) were placed in 92 patients; of these,
      87.9% were placed using a 1-stage technique. The implants were placed in healed
      sites (43.9%), fresh extraction sockets (37.4%), or recent extraction sites (2
      months postextraction) (18.7%). Before restoration, healing times of 3 to 4
      months in the mandible and 5 to 6 months in the maxilla were allowed. The entered
      implant length in the osteotomy site before contacting the bony walls (EILOS) was
      compared, as well as the number of turns and the time required to seat the
      implants. Cumulative survival rates (CSRs) were calculated for up to 18 months of
      follow-up after surgery. RESULTS: The EILOS was between 47.3% and 57.6% of
      implant length for the NT implants; for the standard implants, it was between
      12.0% and 21.2%. With the NT implants, the number of turns and the placement time
      were reduced by 61% to 64% and 61% to 65%, respectively. In the clinical study, 4
      implants failed during the healing period; none failed after prosthesis
      placement. The CSR was 97.79% for implants placed into fresh or recent extraction
      sites; in healed sites, the CSR was 98.75%. The cumulative prosthetic success
      rate was 100%. DISCUSSION: This new implant design is seated with special drills;
      the drilling sequence requires less time and less torque than that used for
      standard implants. The low failure rate after prosthetic loading was consistent
      with that observed for standard Osseotite implants. CONCLUSION: These preliminary
      data suggest that the NT implant can be predictable in healed sites and fresh or
      relatively recent extraction sockets.

PMID- 15973958
TI  - Master cast accuracy in single-tooth implant replacement cases: an in vitro
      comparison. A technical note.
AB  - PURPOSE: This in vitro study evaluated the accuracy of master casts obtained by
      using (1) copings modified by sandblasting and coating their roughened surfaces
      with impression adhesive before final impression procedures and (2) gold machined
      UCLA abutments as impression copings in final impression procedures for single
      tooth implant replacement cases. MATERIALS AND METHODS: A polymeric resin model
      with a standard single implant was used to simulate a clinical situation. A group
      of 20 impressions were made using square impression copings sandblasted to
      roughen their external surfaces at a supragingival level and then coated with
      Impregum polyether adhesive; a second group of 20 impressions were made using
      gold machined UCLA abutments as impression copings. The castable part of the UCLA
      abutments was secured with resin to the gold machined section of the UCLA
      abutment to prevent movement of the castable part itself on the gold machined
      portion during the impression procedures; the castable portion of the UCLA was
      also coated with the Impregum polyether adhesive to improve the stability of the
      gold machined UCLA abutment inside the impression material. Master casts
      fabricated for both groups were analyzed to detect rotational position change of
      the hexagon on the implant replicas in the master casts with reference to the
      resin model. RESULTS: The rotational position changes of the hexagon on implant
      replicas were significantly less variable in the master casts obtained using gold
      machined UCLA abutments as impression copings than in the master casts achieved
      with the roughened square impression copings. DISCUSSION: Improved precision of
      the impression was achieved when the gold machined UCLA abutments were used as
      impression copings. CONCLUSION: This report suggests that using gold machined
      UCLA abutments as impression copings in the final impression procedures can
      enable the clinician to achieve a more accurate orientation of the implant
      replicas in the laboratory master casts for single-tooth implant replacement
      cases.

PMID- 15973959
TI  - Sterility of packaged implant components.
AB  - Several implant components in their original glass vial and peel-back packages
      were subjected to sterility testing to determine whether the contents remained
      sterile after the expiration date marked on the package had passed. The results
      from a university microbiology laboratory showed that the contents remained
      sterile for 6 to 11 years after the expiration dates.

PMID- 15973960
TI  - Surgical template stabilization with transitional implants in the treatment of
      the edentulous mandible: a technical note.
AB  - Proper placement and orientation of dental implants is a requirement for the
      optimum function and esthetics of the definitive restoration. Surgical template
      stability during the surgical phase is a key element in the success of proper
      implant placement. Therefore, any clinical tool that enhances the precision of
      reproduction is of value. This article describes a simple, noninvasive, cost
      effective technique for surgical template stabilization utilizing 2 transitional
      implants placed the same day as the definitive implants.

PMID- 15973961
TI  - Mast cell stabilizator and antioxidant effects of epidermal growth factor (EGF)
      on gastric mucosal injury induced by ethanol in rats.
AB  - The role of epidermal growth factor (EGF), a polypeptide containing 53 amino
      acids, on protection and repair of ethanol-induced gastric mucosal injury was
      investigated in rats. In addition, the effects of EGF on the gastric damage were
      evaluated histopathologically. We used 48 Spraque-Dawley rats which were divided
      into [corrected] three groups as control rats, ethanol treated rats and
      ethanol+EGF treated rats. The ethanol group was given a gastric gavage containing
      1 ml of 80% ethanol (v/v) prepared in distilled water. EGF (100 microg/kg) was
      given by intragastric gavage 30 min before the administration of ethanol. We
      studied histopathological evaluation and the histochemical heterogeneity of mast
      cells and its degree of degranulation. Besides, gastric tissue malondialdehyde
      (MDA), protein sulfhydryl groups (SH), and protein carbonyl levels were measured.
      EGF treatment stabilized mast cells degranulation and had lower polymorphonuclear
      leukocytes (PMNL) infiltration, ulcer index, histamine, and MDA; protein carbonyl
      levels were also lower, compared to the non-treated animals. EGF exerts a
      protective effect on gastric mucosa to ethanol-induced gastric injury probably
      through antioxidant and mast cell stabilizing mechanism.

PMID- 15973962
TI  - Drainage of macromolecules from the Caudato-Putamen of rat brain.
AB  - To study the drainage of interstitial fluid and macromolecules from the brain
      parenchyma, an improved method was developed to inject tracers including Chinese
      ink in group I and phycoerythrin (PE) in group II into the right caudato-putamen
      of rat brain. Rats were sacrificed on the 1st, 3rd, 7th, 14th, 21st day after
      injection in group I and at the 0.5, 1, 2, 5, 24 hour in group II. Distribution
      of tracers was observed by electron microscopy and fluorescence confocal
      microscopy. The results showed that tracers distributed diffusely in the white
      matter at all time points whereas they spread selectively along perivascular
      spaces in the gray matter by 7 days (d) in group I and 5 hours (h) in group II.
      Chinese ink was ingested by perivascular phagocytes by 7 d after ink injection.
      The endothelial cells of capillaries in the gray matter had fluorescence staining
      in cytoplasm and no staining in nuclei by 24 h after PE injection. Animals in
      group II were stained with tracers in lateral ventricles, bilateral cervical
      lymph nodes, and the wall of carotid arteries. These results demonstrated that
      [1] the macromolecules could be cleared from the caudato-putamen through
      extracellular space of the neuropil in the white matter and perivascular space in
      the gray matter, [2] perivascular phagocytes and endothelial cells of capillaries
      played important roles in clearing macromolecules from the perivascular space,
      and [3] cervical lymph nodes were involved in draining macromolecules from the
      brain parenchyma.

PMID- 15973963
TI  - Reduction of ventricular hypertrophy and fibrosis in spontaneously hypertensive
      rats by L-arginine.
AB  - The purpose of this experiment was to explore long-term L-arginine administration
      on ventricular hypertrophy and cardiac fibrosis in spontaneously hypertensive
      rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Twenty-four rats of each
      strain at eight wks of age were divided into two groups--one receiving L-arginine
      and the other vehicle for twelve wks. Arterial pressure (AP) and heart rate were
      monitored. At 20 wks of age, the rats' rings of thoracic aorta were isolated to
      record isometric tension. The study measured left ventricular weight (LVW), body
      weight (BW), left ventricular (LV) contents of cGMP, and collagen volume fraction
      (LVCVF). Histological examination of the LV tissue determined changes in
      cardiomyocytes. Administration of L-arginine did not alter the AP change in SHR,
      but reduced the AP in WKY after six wks. Our results showed a significantly
      higher LVW/BW ratio and LVCVF in vehicle-treated SHR compared to levels in
      corresponding WKY, whereas, the LV cGMP and nitrite/nitrate measurements were
      higher in vehicle-treated WKY than in SHR. L-Arginine treatment decreased LVW/BW
      ratio and LVCVF, while increasing the levels of LV cGMP and nitrite/nitrate only
      in SHR, consistent with histopathological examinations that showed L-arginine
      prevented cardiomyocytes from thickness and hypertrophy. Our results suggested
      that the mechanism of reduction in ventricular hypertrophy and fibrosis following
      long-term L-arginine administration in SHR may stem from increased myocardial
      nitric oxide-cGMP signaling, independent of AP and EDV of thoracic aorta.

PMID- 15973964
TI  - Interactive effect of an acute bout of resistance exercise and
      dehydroepiandrosterone administration on glucose tolerance and serum lipids in
      middle-aged women.
AB  - The present study determined the interactive effect of an acute bout of
      resistance exercise and dehydroepiandrosterone (DHEA) administration on glucose
      tolerance and serum lipids. Twenty middle-aged female subjects performed an acute
      bout of resistance exercise and were subsequently divided into two groups:
      placebo (age 40.7 +/- 2.0) and DHEA administered (age 39.0 +/- 2.7). Ten subjects
      who received DHEA (age 41.5 +/- 4.6) participated in a non-exercise control. DHEA
      (25 mg twice daily) or placebo was orally supplemented for 48 hours. Before
      exercise and 48 hours after the last exercise bout (14 hours after the last DHEA
      intake), an oral glucose tolerance test and an insulin concentration were
      determined. Levels of fasting serum cholesterol and triglyceride, tumor necrosis
      factor-alpha (TNF-alpha), creatine kinase (CK) were also measured. The DHEA
      administration significantly elevated the fasting dehydroepiandrosterone sulfate
      (DHEA-S) level by approximately 3-fold. Both acute resistance exercise and DHEA
      administration improved glucose tolerance, but no addictive effect was found.
      Furthermore, exercise and DHEA administration did not affect serum triglyceride
      and cholesterol levels, but both lipids were significantly lowered when DHEA was
      given following exercise. Resistance exercise induced elevations in serum CK and
      TNFalpha levels, but these increases were attenuated by the DHEA administration.
      The new finding of this study was that post-exercise DHEA administration
      decreased serum triglycerides and cholesterol. This effect appeared to be
      associated with its TNF-alpha lowering action.

PMID- 15973965
TI  - Preganglionic neurons of the sphenopalatine ganglia reside in the dorsal facial
      area of the medulla in cats.
AB  - Stimulation of the sphenopalatine ganglion (SPG), a parasympathetic ganglion of
      the facial nerve, or the dorsal facial area (DFA), an area in the lateral
      tegmental field just dorsal to the facial nucleus, induces an increase in blood
      flow of the common carotid artery (CCA). This study attempted to clarify the
      anatomical and functional relationships between the SPG and the DFA, and to
      demonstrate putative serotonergic (5-HT) and substance P (SP) innervations to the
      neurons of the DFA in regulation of the CCA blood flow in cats. Horseradish
      peroxidase (HRP), a retrograde tracer, was injected in the SPG. All HRP-labeled
      neurons were distributed in the reticular areas dorsal and lateral to the
      superior olivary nucleus and the facial nucleus, extending from the caudal half
      of the superior olivary nucleus to the rostral 3/4 of the facial nucleus on the
      HRP-injected side. They were grouped into five clusters, namely lateral
      circumference of the superior olivary nucleus, dorsal circumference of the
      superior olivary nucleus, lateral circumference of the facial nucleus, dorsal
      circumference of the facial nucleus, and the DFA. The percentage of HRP-neurons
      in each cluster was 0.5 +/- 0.1% (mean +/- S.E., n=6), 15.2 +/- 1.9%, 23.7 +/-
      0.9%, 52.5 +/- 1.7%, and 8.3 +/- 0.7%, respectively. Glutamate stimulation of the
      DFA (at 5.0 to 7.0 mm rostral to the obex, 2.8 to 4.0 mm lateral to the midline,
      and 2.5 to 3.5 mm ventral to the dorsal surface of the medulla), but not other
      areas, resulted in the increased CCA blood flow. The 5HT- and SP-immunoreactive
      nerve terminals abutted on the ChAT-immunoreactive cell body (preganglionic
      neurons) in the DFA. In conclusion, parasympathetic preganglionic neurons in the
      DFA project fibers to the SPG, are innervated by 5HT- and SP-like nerve
      terminals, and are responsible for regulation of the CCA blood flow. They may be
      also important in regulation of the cerebral blood flow.

PMID- 15973966
TI  - Acute effects of d-amphetamine on the differential reinforcement of low-rate
      (DRL) schedule behavior in the rat: comparison with selective dopamine receptor
      antagonists.
AB  - Amphetamine and it analogs have been shown to affect operant behavior maintained
      on the differential reinforcement of a low-rate (DRL) schedule. The aim of the
      present study was to investigate what specific component of the DRL response is
      affected by d-amphetamine. The acute effects of d-amphetamine on a DRL task were
      compared with those of the selective dopamine D1 and D2 receptor antagonists,
      SCH23390 and raclopride, respectively. Pentylenetetrazole and ketamine were also
      used as two reference drugs for comparison with d-amphetamine as a
      psychostimulant. Rats were trained to press a lever for water reinforcement on a
      DRL 10-s schedule. Acute treatment of d-amphetamine (0, 0.5, and 1.0 mg/kg)
      significantly increased the response rate and decreased the reinforcement in a
      dose-related fashion. It also caused a horizontal leftward shift in the inter
      response time (IRT) distribution at the doses tested. Such a shifting effect was
      confirmed by a significant decrease in the peak time, while the mean peak rate
      and burse response remained unaffected. In contrast, both SCH23390 (0, 0.05, and
      0.10 mg/kg) and raclopride (0, 0.2, and 0.4 mg/kg) significantly decreased the
      total, non-reinforced, and burst responses. The de-burst IRT distributions were
      flattened out as shown by the dose-related decreases in the mean peak rate for
      both dopamine antagonists, but no dramatic shift in peak time was detected.
      Interestingly, neither pentylenetetrazole (0, 5, and 10 mg/kg) nor ketamine (0,
      1, and 10 mg/kg) disrupted the DRL behavioral performance. It is then conceivable
      that d-amphetamine at the doses tested affects the temporal regulation of DRL
      behavior. The effectiveness of d-amphetamine is derived from its drug action as a
      psychostimulant. Taken together, these data suggest that different behavioral
      components of DRL task are differentially sensitive to pharmacological
      manipulation.

PMID- 15973967
TI  - Effects of asphyxia on arterial blood pressure, formation of nitric oxide in
      medulla and blood parameters in the cat.
AB  - The rostral ventrolateral medulla (RVLM) plays an important role in the
      integration of cardiovascular functions. We examined the effect of asphyxia on
      cardiovascular responses, on sympathetic vertebral nerve activity (VNA) and
      nitric oxide (NO) formation in the RVLM, on hemodynamics, and on plasma
      concentrations of catecholamines, blood gas partial pressures and carbohydrate
      metabolites. Using 16 anesthetized cats we found that the systemic arterial
      pressure (SAP), VNA, NO formation and the release of plasma catecholamine
      components of norepinephrine and epinephrine were increased during asphyxia. The
      onset of NO production was significantly earlier than that of SAP and VNA. The
      venous partial pressure of O2 decreased, while the partial pressure of CO2
      increased. Furthermore, metabolism of glucose and lactate increased, as did the
      blood concentrations of white and red blood cells, hemoglobin and platelets.
      Thus, asphyxia increased SAP, VNA and NO formation. It increased the plasma
      catecholamines, blood gases, carbohydrate metabolites and blood cells.

PMID- 15973968
TI  - Effects of streptozotocin-induced diabetes on Kv channels in rat small coronary
      smooth muscle cells.
AB  - Diabetes impairs endothelium dependent vasodilation, but the mechanism of
      endothelium independent dilation is not well understood. In the present study, we
      examined the effect of streptozotocin (STZ)-induced diabetes on the vasomotor of
      small coronary artery and the activity of voltage-dependent K+ channel of
      vascular smooth muscle cells in STZ rats [corrected] using the videomicroscopy
      and patch clamp method. STZ-induced diabetes appeared to [corrected] reduce the
      vasodilation induced by beta-adrenoceptor agonist, isoproterenol (10(-9)-10(-5)
      mol/l), and adenylyl cyclase activator forskolin (10(-9)-10(-5) mol/l)
      respectively (isoproterenol: 44.2 +/- 6.7% vs. 82.5 +/- 4.8%, and forskolin: 54.4
      +/- 4.5% vs. 94.3 +/- 2.4%). 4-AP, a Kv channel blocker of VSMC, further
      decreased dilation to isoproterenol (44.2 +/- 6.7% vs. 10.2 +/- 3.5%) and
      forskolin (54.4 +/- 4.5% vs. 13.8 +/- 11.0%) significantly. Whole cell K+ current
      recording demonstrated that STZ-induced diabetes decreased isoproterenol and
      forskolin-induced K+ current (ISO: 55.6 +/- 7.8 pA/pF vs. 28.4 +/- 3.4 pA/pF,
      forskolin: 61.3 +/- 9.8 pA/pF vs. 32.4 +/- 3.4 pA/pF). 4-AP further reduced the
      decreased K+ current (ISO: 28.4 +/- 3.4 pA/pF vs. 14.3 +/- 2.1 pA/pF, forskolin:
      32.4 +/- 3.4 pA/pF vs. 14.8 +/- 2.9 pA/pF). These results indicated that STZ
      induced diabetes impaired cAMP mediated dilation of small coronary artery and
      suppressed the Kv channel activity of vascular smooth muscle cells. Kv channel of
      VSMC was shown to play a determinate role reducing dilation of small coronary
      artery in STZ rats.

PMID- 15973969
TI  - Tobacco smoking and vertical periodontal bone loss.
AB  - Cigarette smoking is associated with increased prevalence and severity of
      destructive periodontal disease in terms of periodontal pocketing, periodontal
      bone loss, and tooth loss. The smoking destructive effect on periodontal bone may
      be of even "horizontal" and vertical "angular" pattern. The vertical bone loss or
      the "vertical defect" is a sign of progressive periodontal breakdown that
      involves the periodontal bone. Water pipe smoking has a sharp rise by the
      popularity in the recent years by men and women in Middle East countries. The
      general objective of this thesis was to investigate the relationship between
      tobacco smoking and vertical periodontal bone loss cross-sectionally and
      longitudinally. This thesis is based on two study populations, Swedish musicians
      and a Saudi Arabian population. All participants had a full set of intra-oral
      radiographs including 16 periapical and 4 bitewing projections that were assessed
      with regard to presence or absence of vertical defects. In Study I, the number of
      defects per person increased with age. Vertical defects were more common in the
      posterior as compared to the anterior region of the dentition and the
      distribution of defects within the maxilla as well as the mandible typically
      revealed a right-left hand side symmetry. Cigarette smoking was significantly
      associated with the prevalence and severity of vertical bone defects (Studies II
      and III). The relative risk associated with cigarette smoking was 2 to 3-fold
      increased. The impact of water pipe smoking was of the same magnitude as that of
      cigarette smoking and the relative risk associated with water pipe smoking was 6
      fold increased compared to non-smoking. In addition, the risk of vertical defects
      increased with increased exposure in cigarette smokers as well as water pipe
      smokers (Study III). In Study IV, the proportion of vertical defects increased
      over a 10-year period and the increase over time was significantly associated
      with smoking. Moreover, the 10-year vertical bone loss was significantly greater
      in heavy exposure smokers than in light exposure smokers suggesting an exposure
      response effect of smoking. Compared to non-smokers the 10-year relative risk was
      2.4-fold increased in light exposure smokers and 5.8-fold increased in heavy
      exposure smokers. In conclusion, the present observations indicate that there is
      a significant relationship between tobacco smoking and vertical periodontal bone
      loss. Tobacco smoking should be considered a risk factor for periodontal vertical
      bone loss.

PMID- 15973970
TI  - [Healthcare professionals' knowledge of blood pressure measurement].
AB  - This study investigated the theoretical and technical knowledge of blood pressure
      measurement from 110 nursing assistants, 44 physicians and 25 nurses by answering
      to a questionnaire and practical knowledge through the observation of the blood
      pressure measurement procedure. In the theoretical knowledge the three categories
      showed statistically significant differences (p<0,05), the nursing assistants
      showed a lower indicator of the correctness (32%+/-12%) followed by nurses (44%+/
      14%) and physicians (56%+/-13%). In the practical knowledge the physicians showed
      higher percentage of correctness (50%+/-12%) (p<0.05);followed by nurses (44%+/
      10%) and nursing assistants (41%+/-6%). In conclusion, the knowledge of blood
      pressure measurement was not satisfactory.

PMID- 15973971
TI  - [Intramuscular drug administration: analysis of knowledge among nursing
      professionals].
AB  - Using a questionnaire with open and closed questions, this study aimed to: verify
      among nursing professionals which are the most used regions for intramuscular
      medication application; identify the method they use for delimiting the puncture
      regions and site; identify their knowledge of complications and contraindications
      of using the regions and verifying the use of the ventrogluteal region. Thirty
      two professionals participated in the study, which used the dorsogluteal (65.62%)
      and deltoid (31.25%) regions. The need for updating these professionals was
      disclosed, especially regarding to anatomy, the adequate terminology used for
      designating the regions and the knowledge of complications and contraindications.
      Investments in training these professionals are essential for using the
      ventrogluteal region.

PMID- 15973972
TI  - [Description and analysis of "embracement": a contribution to the family health
      program].
AB  - The humanist and efficient healthcare required by the Family Health Program makes
      the "embracement" essential. This study aimed to identify how the "embracement"
      was developed at Family Healthcare Services in Sao Paulo, SP. Brazil. The authors
      observed several "embracement" links and interviewed healthcare professionals.
      The results pointed out the clinical and biological focuses of the "embracement".
      They also showed that "embracement" resolution is limited and does not entail
      bounding. To make the healthcare services more accessible, according to the
      proposal of the National Health System, the theoretical and practical
      perspectives of the "embracement" must be reviewed.

PMID- 15973973
TI  - [Study on stress among nurses working in two shifts at a pediatric oncology
      hospital in Campinas].
AB  - This is a study that aimed investigating the presence and level of emotional
      stress, the physical and psychological symptoms, the intensity of stress and
      nurses who have two work shifts compared to the ones who don't have it at a
      pediatric oncology hospital in Campinas. The population was made of 33 nurses in
      which 24 work in two shifts and 9 work in just one. In the methodology, it was
      used the LIPP Stress Symptom Inventory and the Visual Analogical Scale. The
      results enabled us to confirm that nurses classified regarding to their stress
      phases were on the resistance phase, regarding to the stress level they were on
      the average stress level. There was a predominance of psychological symptoms and
      nurses who had two work shifts were more stressed than the ones with only one
      shift.

PMID- 15973974
TI  - [Emotional states of nurses in professional performance at intensive care units].
AB  - The aim of is study was to analyze the nurses' psychological variables taken firm
      Engelmann's List of Emotional States and based on the questionnaire answered by
      the subjects at the begining and end of each shift in different units of Hosptal
      das Clinicas, UNICAMP on the six-hour and twelve-hour schedules in activities
      developed at the surgical center (SC), Intensive Care Unit (ICU, Coronary Unit
      (CU) and Emergency Room (ER) with the averge age of 33.88 years old. The results
      allowed us to certify the nurses' emotional parameters have alterations during
      the shift which can be related to the burnout and stress of the care delivery
      activity, even more in units where it demands immediate answers kill and need on
      emergency. Tiredness was a strong variable at the end of the shifts in all units.
      The results obtained at the beginning and end of the shifts were statisically
      compared using the Kruskal-Wallis method and the group profiles demonstrated a
      variety of feelings and intensities that were statistically significant (p=pounds
      sterling 0.05).

PMID- 15973975
TI  - [The real and the idealized teacher as envisioned by a group of graduating
      nurses].
AB  - This survey, carried out in two colleges of nursing, is an attempt to contribute
      to the understanding of the teaching of nursing by characterizing the real and
      idealized professor, as seen by undergraduate students; identifying the most
      valued areas of the teacher's performance: the emotional side or that related to
      specific theoretical-practical prowess and the didactic-pedagogic aspects as well
      as identifying the differences in attitudes between the students in relation to
      these values. The data were obtained through the application of 69
      questionnaires. After descriptive analysis of the results, it was concluded that
      the emotional aspects of the teacher-student relationship are mediators through
      which the mastery of the subject content and also the didactic-pedagogic aspects,
      as well as, the teaching-learning process are achieved with success.

PMID- 15973976
TI  - [Nursing teaching in middle level of a technical course: the use of a facilitator
      strategy with recyclable material].
AB  - The objective of this study was developing facilitator strategies in the teaching
      and learning process, using recyclable materials in the medical-surgical nursing
      discipline for 31 students in a middle level course on the formation of nursing
      assistants. After studying bibliographical references related to Anatomy,
      Physiology and most common Pathologies in the several systems of the human body,
      the students selected the disposable recyclable materials for the confection of
      the main anatomical structures, which made it possible the visualization of the
      morphologic alterations, facilitating the understanding of the clinic-surgical
      diseases. The use of these strategies enabled the acquisition of knowledge when
      they projected in something concrete, result of the exchange of suggestions and
      experiences among the students, favored by group work.

PMID- 15973977
TI  - [Nursing undergraduate students and their relationship with smoking].
AB  - This study was designed to investigate: the prevalence of smokers among the
      UNIFESP nursing undergraduate students; some initial usage features; the smokers'
      dependence degree on nicotine. In order to compare the ratio of some variables,
      Pearson's Square Chi test was applied. The number of smokers among the nursing
      undergraduate students in the sample was 23 (8.2%) and 167 (59.9%) said they had
      never smoked a cigarette. Smokers' average age was 19.5 years old, and there is a
      significant difference between genders and only 2 (9.1%) smoking students may
      show a more severe discomfort while attempting to stop smoking, as showed the
      Fagerstrom's Test.

PMID- 15973978
TI  - [Health education for the mentally ill: a first-hand account].
AB  - The account in this text refers to an effective health education project in a
      Mental Health post in Sao Paulo for which nursing department students are
      responsible. The belief in the mentally ill person conquering rights as citizens
      as well as understanding that the education may become the individual's most
      valuable emancipation tools were the starting point of the project. There was a
      short phase as well as a long one, both of which occurred in the weekly open
      group format to users and their family members, and whose characteristics were
      free participation, since the space was open for discussion and the exchange of
      both opinions and experiences. The themes were chronic illnesses, and those
      highlighted ones were mental illnesses, communicable diseases and chronic
      degenerative-illnesses.

PMID- 15973979
TI  - [Family and mental disease: the difficulty of living with differences].
AB  - This study started from the reflections on the Psychiatric Care Reform and the
      desinstitutionalization process. The goal of this study is to identify the social
      representations built by the patients' relatives on the mental health-disease
      phenomenon. For analysis we have adopted the social representation referential
      through the Moscovici perspective. Eight relatives of the patients were
      interviewed. We have identified the mentioned relatives, considering those who
      are really different, as the center of their social representations. We have
      point out the importance of the mental health professionals to give careful
      considerations on their interventions, regarding to the knowledge emerged from
      the report of the patients' relatives.

PMID- 15973980
TI  - [Self-esteem and nonverbal signs of burn patients].
AB  - This research aimed to identify the self-esteem degree and the nonverbal signs of
      the Burn Center patients at HC-FMUSP. Those signs complement, contradict or
      demonstrate the patients'feelings when they are asked about their self-esteem.
      The project was accomplished with 80 patient (54 women and 26 men) attended in
      the hospital in February 2002. It has been approved by the Commissions of Ethics
      on Research of EEUSP and HC-FMUSP. The individual interviews with the patients
      were based on the scale of self-esteem validated in Brazil and also based on the
      classification of the nonverbal signs proposed by Silva. Through the results we
      verified that 18.75% patients present low self-esteem, 32.50% medium self-esteem
      and 48.75% high self-esteem. We also concluded that the complement was the
      function of the nonverbal signs, more often during the interviews.

PMID- 15973981
TI  - [Simplified version of the therapeutic intervention scoring system and its
      prognostic value].
AB  - The study evaluates the competence of the "TISS-28" to distinguish inpatients at
      the ICU, between the ones likely to die from the ones likely to survive and to
      establish a threshold score for high likelihood to death. The findings obtained
      by the sample of 200 inpatients at 14 ICUs in Sao Paulo County showed that the
      TISS-28 presented association with mortality (p=0.0001). The cutting score
      established was 21. It was found that 80.88% of those who died had the TISS-28
      score similar or higher and 68.18% of survivors had the score below 21.
      Furthermore, regarding to the prognostic value of TISS-28, it was showed up the
      accuracy of 0.72.

PMID- 15973982
TI  - [An important mission for microbiologists in the new century-cultivation of the
      unculturable microorganisms].
AB  - The present review summarizes the recent advances in cultivating the so-called
      recalcitrant microorganisms in various natural environments. Firstly, the use of
      new electron donors and acceptors reveals a list of unique and previously
      unrecognized physiotypes (Table 1), and the growth supporting reactions include
      oxidation of phosphite, arsenite, soil humic substances, benzene, Fe (II) and
      aryl-halides. The novel pure cultures obtained include: Desulfatogenum
      phosphitoxidans, lithochemotrophic arsenite oxidizing bacteria, Dechloromonas
      agitata, Dechalosoma suillum, and various Proteobacteria capable of decomposing
      soil humic substances anaerobically. Secondly, the adaption of nutrient-poor
      media (down to 1/100 of the traditional concentration), including sea water, soil
      extract and extension of natural habitats (insect hind-gut, submarine hot vent)
      are extremely rewarding. For example, cultivation of the ubiquitous SAR11 marine
      bacterioplankton clade reveals a phylum, small in cell size and genome, but
      dominating in ocean surface, thus constituting a huge biomass on earth. In
      addition, the nanosized hyperthermophilic Archaeon from a submarine hot vent,
      represents an unknown phylum, and because of its symbiotic living with Ignicocous
      cells, it is named Nanoarchaeum equitans. Its genome size is only 500kb, the
      smallest for prokaryote. Considering its hyperthermic living environment and
      small genome, N. equitans may possibly still a primitive form of microbial life
      and affords an advantageous culture for the study of life origin and evolution on
      earth. Thirdly, several novel isolation techniques have been developed such as
      gel microdrop encapsulation and diffusion chamber, both with the advantages of
      high-throughout operation and simulating to certain extent of the natural
      environment, thus allowing growth synergy based on cross-feeding to occur.
      Finally, it should be noted that the cultivation of unculturable microorganisms
      mentioned in this review does not require expensive and sophisticated equipments
      and most of the techniques can be adapted in our laboratory at home.

PMID- 15973983
TI  - Feedback-insensitive anthranilate synthase gene as a novel selectable marker for
      soybean transformation.
AB  - Because of the concern about escape of antibiotic- or herbicide-resistant
      transgenes from transgenic crops, selectable marker genes from plant origin would
      be an alternative choice for plant transformation. In this study, a feedback
      insensitive anthranilate synthase gene ( ASA2 ) cloned from a tobacco cell line
      was tested for Agrobacterium-mediated transformation of axis tissue of soybean
      mature embryo, with a tryptophan analogue 5-methyltryptophan (5-MT) as the
      selective agent. Southern blot analysis of the To transgenic lines confirmed the
      integration of the ASA2 gene into the soybean genome. Northern blot analysis
      showed the ASA2 gene was also expressed in the leave tissue, and the free
      tryptophan content in the leaf tissue of transgenic soybean was about 59% to 123%
      more than that in the wild type. PCR analysis of the T1 progeny showed that the
      transgene was inherited in a Mendelian fashion. All these results indicate that
      this feedback-insensitive ASA2 gene can be used as a selectable marker gene for
      plant transformation. This work also demonstrated that the ASA2 gene coding for
      the a-subunits from one plant (tobacco) can interact with the n-subunits of a
      heterologous plant (soybean) to form an active anthranilate synthase enzyme. The
      use of this feedback-insensitive gene as a novel selectable marker for plant
      transformation is also discussed.

PMID- 15973984
TI  - [Expression, purification and characterization of the recombinant anthrax
      protective antigen].
AB  - An expression plasmid carrying anthrax protective antigen (PA) gene was
      constructed, which has an OmpA signal sequence attached to the 5' end of PA gene.
      The plasmid was transformed into E. coli and induced to express recombinant PA
      (rPA) . The recombinant protein, about 10% of the total bacterial protein in
      volume, was secreted to the periplasmic space of the cell. After a purification
      procedure including ion-exchange, hydrophobic interaction chromatography, and gel
      filtration, about 15 mg of 95 % pure rPA was obtained from 1-liter culture. The
      bioactivity of rPA was proved by in vitro cytotoxicity assay. The polyclonal
      antiserum from rabbits immunized with rPA could inhibit the action of anthrax
      lethal toxin in vitro, which suggests that antibodies against rPA can provide
      high passive protection against anthrax. The results reported here may be helpful
      to develop a safe and efficacious recombinant PA vaccine against anthrax.

PMID- 15973985
TI  - [Cloning and superexpression of cry1Ac gene from 20kb DNA associated with
      Bacillus thuringiensis Cry1A Crystal Protein].
AB  - The CrylA Crystal Protein from Bacillus thuringiensis is associated with DNA, but
      the role and sequences of these DNA molecules are unknown. CrylA bipyramidal
      crystals from B. thuringiensis strain 4.0718 was selectively dissolved and
      associated DNA was extracted from protoxin. The DNA was digested with Nde I to
      obtain 3 to 5 kb fragments and then the fragments were subcloned into pMD18-T
      vector, screening of recombinants were done by PCR-RFLP and sequencing. The ORF
      of cry1Ac gene was amplified by primers designed and then subcloned. The 3.5 kb
      BamH I and Sal I fragments of pMDX35 was inserted into the pET30a vector, giving
      8.9 kb recombinant plasmid, pETX35. ETX35 strain were obtained by transformed
      pETX35 into B121 (DE3). A 141 kD fusion protein was superexpressed as inclusion
      bodies. Quantitative protein analysis indicated that the amount of 141 kD protein
      was above the level of 51.36% of total cellular protein. Plasmid pHTX42
      constructed from shuttle vector pHT304 was transformed B. thuringiensis
      acrystalliferous strain XBU001 with electroporation to obtain the recombinant
      HTX42. The recombinant protein was found with a molecular mass of 130 kD on
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Scanning
      analysis indicated that the expressed protein accounted up to 79.28% of total
      cellular proteins and accumulated in the cells mounted up to 64.13% of cellular
      dry weight. Under Atomic Force Microscopy (AFM), typical bipyramidal crystals
      from HTX42 strain were found with a size of 1.2 microm x 2.0 microm. Bioassay
      showed that these inclusion bodies of ETX35 strain and crystals from HTX42 strain
      were highly toxic against the larvae of Plutella xylostella. On such a base,
      constructing insecticidal recombinant and analyzing the source, structure, and
      function of the 20 kb DNA can be further achieved.

PMID- 15973986
TI  - [Construction of efficient conjugal plasmids between Escherichia coli and
      Streptomycetes].
AB  - Conjugal plasmid pGH112 has been developed based on the replicons of Streptomyces
      coelicolor plasmid SCP2 and E. coli ColE. The plasmid contains ampicilin
      resistance gene(amp) for selection in E. coli and thiostrepton resistance gene
      (tsr) for selection in Streptomycetes, and a 0.76 kb oriT fragment of (IncP) RK2.
      Conjugal transfer of pGH112 was performed from E. coli to S. coelicolor A3(2), S.
      avermitilis, S. lividans TK54, S. toxytricini NNRL15443, S. venezuelae ISP5230
      and Sacc. erythraea by conjugation, results show that the plasmid was able to
      transfer efficenctly from E. coli to Streptomycetes, was stably inherited in the
      recipients. pGH113 was constructed from pGH112 by combining the constitutive ermE
      promoter with green fluorescent protein gene(gfp).

PMID- 15973987
TI  - [Construction of phage display antibody library to MCF-7 cells and screening of
      single-chain antibodies against breast cancer cells].
AB  - The aim of this study is to construct a phage display single-chain variable
      fragment (scFv) library against breast cancer cells and screen the specific
      antibodies against MCF-7 cells from the library. The BALB/C mice were immunized
      with MCF-7 cells. Total RNA of spleens was isolated. The heavy-chain (VH) and
      light-chain variable region genes (VL) of the antibodies were amplified by RT-PCR
      and joined into a single chain by overlapping PCR with a linker DNA encoding the
      peptide (Gly4Ser)3. The assembled scFv fragments were cloned into the
      phagemids(pCANTAB5E) and the recombinant phagemids were used to transform
      competent E. coli TG1. The transformed TG1 cells were infected by helper phage
      M13KO7 and the recombinant phagemids were rescued. The scFv fusion proteins were
      displayed on the surfaces of the recombinant phages. A phage display antibody
      library of repertoire of 1.2 x 10(6) clones was constructed. The specific
      antibodies against MCF-7 cells were enriched by 75 times after five rounds of
      affinity selection. Ten recombinant phages clones that exhibited specific binding
      to MCF-7 cells were identified. The specificity of those phage clones was
      analyzed by reactivity against HepG2 cells and Hela cells by ELISA. One of the
      selected phage clones against MCF-7cells was used to infect E. coli TOP10 to
      produce the soluble scFv antibodies after induction with IPTG. The strategy of
      construction and screening of antibody library directed against the whole tumor
      cells described in this report should be generally applicable to generate tumor
      cell-specific antibodies.

PMID- 15973988
TI  - [High level expression of chimeric antibody fragment F(ab')2 directed against
      CD20 in Escherichia coli].
AB  - The use of tumor antigen specific antibody for the delivery of therapeutic agents
      offers the possibility of targeting therapy with reduced toxicity to normal
      tissues compared to conventional treatments. In previous work, the human-mouse
      chimeric antibody fragment Fab' directed against CD20 was constructed from the
      new anti-CD20 antibody HI47 (a mouse IgG3, K). The chimeric antibody fragment
      Fab' could reduce its antigenicity, but the yield, quality and affinity of
      chimeric antibody fragment Fab' restrict its use. To improve affinity of chimeric
      antibody fragment Fab', a new phasmid pYZcpp3, which expresses chimeric antibody
      fragment F(ab')2, was constructed by adding a sequence encoding a small peptide,
      (CPP)3, to C-terminus of heavy chain constant region of chimeric antibody
      fragment Fab'. Using the pYZcpp3 to transform E. coli. 16c9, the genetically
      engineered bacteria 10916# was obtained. 10916# can secret the soluble chimeric
      antibody fragment Fab' and F(ab')2 into periplasmic. The yield was up to 360 mg/L
      with the percent of F(ab')2 up to 45% in 19L fermentor by the high density
      fermentation technology. Without denaturation and renaturation, the F(ab')2 has
      possessed the native three-dimensional structure. The purity of F(ab')2 was more
      than 90% after the purification of protein G affinity chromatography and S200
      size exclusion chromatography. The F(ab')2 could distinguish and bind to Raji
      cells (CD20+) by FACS. F(ab')2 could inhibit the proliferation of Raji cells in
      vitro by MTT, IC50 was 22.8 microg/mL. HI47 and its chimeric fragments F(ab')2
      induced a significant level of apoptosis (23.5%, 20.8%, respectively),
      independent of any cross-linking agents, in Raji cells after 24 h incubation. The
      chimeric antibody fragment F(ab')2 directed against CD20 is possible to apply to
      tumor therapy in clinic in the future.

PMID- 15973989
TI  - [Novel methods to detect cytokines by enzyme-linked oligonucleotide assay].
AB  - The development of the systematic evolution of ligands by exponential enrichment
      (SELEX) process has made it possible to isolate oligonucleotide sequences with
      the capacity of recognizing virtually any class of target molecules with high
      affinity and specificity. These oligonucleotide sequences, referred to as
      "aptamers", are useful as a class of molecules that rival antibodies in
      diagnostic applications. Aptamers are different from antibodies, yet they mimic
      properties of antibodies in a variety of diagnostic formats. To meet the
      shortcomings of antibodies, aptamers have the following advantages. Aptamer does
      not depend on animals, cells, or even in vivo conditions and produced by chemical
      synthesis with extreme accuracy and reproducibility. Once denatured, functional
      aptamers could be regenerated easily within minutes. They are stable to long-term
      storage and can be transported at ambient temperature. We describe here an enzyme
      -linked oligonucleotide assay that use a SELEX-derived RNA aptamer to detect
      hTNFalpha. In order to protect from nuclease attack, the RNA aptamer was modified
      by replacement of 2'-NH2 for 2'-OH at all ribo-purines. In a sandwich micro-plate
      assay, hTNFalpha monoclonal antibody was coated on the surface of the plate,
      biotin-labeled RNA aptamer was used as a detect molecle. HTNFalpha was diluted by
      pooled human serum as standard, and streptavidin-horseradish peroxidase-substrate
      system was added for detection. Accuracy, precision, sensitivity, specificity of
      ELONA method were analyzed. The levels of hTNF-alpha in normal human serum
      samples were assayed by the ELONA and the ELISA processes. The resultes
      demonstrate that a sandwich assay using a SELEX-derived RNA aptamer has
      parameters for accuracy, precision, sensitivity, specificity well within the
      limits expected of a typical enzyme-linked assay. There is no significant
      difference between the results of ELONA and ELISA. The minimum detection level
      was 100 pg/mL. This method will be useful for detection of almost all the
      cytokines and other protein molecules.

PMID- 15973990
TI  - Humoral immune response elicited by plasmid DNA containing HGV E2 gene fragment.
AB  - In order to study the feasibility of E2 gene fragment of hepatitis virus G(HGV)
      as a component of DNA vaccine against the hepatitis virus G infection, a 559bp
      DNA fragment encoding HGV E2 was cloned into plasmid pCMV-S from pThioHis-E2 in
      the same reading frame with HBsAg gene to form a recombinant plasmid named pCMV-S
      E2. BALB/c mice of Kunming strain were immunized with purified plasmid DNA of
      pCMV-S-E2 by intra-muscularly inoculation. The immunizations were boosted twice
      at an interval of 14 days. The whole blood was collected from mice orbit on the
      day-8 after the last boost. Mice sera were screened by ELISA to determine the
      humoral immune response using E2-GST fusion protein as the immobilized antigen
      and the sera from mice immunized with pCMV-S as control. The result indicated
      that the immunization with plasmid DNA of pCMV-S-E2 could induce quite strong
      humoral immune response.

PMID- 15973991
TI  - [Expression, purification and specific monoclonal antibodies preparation of
      diphtheria toxin A fragment].
AB  - Diphtheria toxin A fragment (DTA) is an essential catalytic domain of diphtheria
      toxin (DT)-based immunotoxin. DTA protein and its antibodies play an important
      role in the studies on toxicology, purification and identification of DT-based
      immunotoxins. In this paper, DTA was expressed and purified from E. coli. After Q
      Sepharose FF chromatography and (Ni+)-Sepharose affinity chromatography, 6 x His
      DTA fusion protein with 90% purity was achieved. Using the purified DTA as
      antigen to immunize BalB/c mice, 2 hybridoma cell lines (designated as 3B6 and
      3B9, respectively) secreting monoclonal antibodies (McAbs) against DTA were
      established. Investigations showed that both McAbs were characterized as IgG1
      with titers of 1: 10(6). The binding of the McAbs to DTA was competitively
      inhibited by horse sera against DT. The fact that anti-DTA McAbs could be used in
      western blot analysis and affinity chromatography purification of DT-based
      immunotoxins implied that they will be useful agents in the studies on DT-based
      immunotoxins.

PMID- 15973992
TI  - [Expression of prostate stem cell antigen (PSCA) and selection of its specific
      binding peptide].
AB  - Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell
      surface antigen, is expressed by a majority of human prostate cancers and is a
      promising target for prostate cancer immunotherapy. To obtain the specific
      peptide binding with PSCA for targeted immunotherapy, PSCA gene was obtained by
      RT-PCR from human prostate cancer cell line DU145 and the transcated PSCA (tPSCA)
      gene was cloned into vector pQE30 for soluble expression in E. coli. The identity
      of recombinant tPSCA was confirmed through ELISA and western blot by use of anti
      PSCA monoclonal antibody. Then the 12-peptide phage display library was screened
      with the purified tPSCA protein for its specific binding peptide through 3 rounds
      panning. For identifying the peptide's specificity, the peptide was coupled with
      EGFP (enhanced green fluorecent protein) by recombinant DNA technology and the
      recombinant coupled protein was termed 11-EGFP. The binding specificity with
      tPSCA of 11-EGFP was further confirmed by ELISA and competitive inhibition
      experiment. Flow cytometry demonstrated its binding specificity with cell line
      DU145. In conclusion, a 12-amino-acid peptide which could bind with PSCA
      specifically was found and it may be a potential tool for targeted immunotherapy
      of prostate carcinoma.

PMID- 15973993
TI  - [Eukaryotic expression and functional characterization of PD-1 extracellular
      domain].
AB  - The negative signal provided by interactions of costimulatory molecules,
      programmed death-1 (PD-1) and its ligands, PD-L1 (also B7-H1) and PD-L2 (also B7
      DC), is involved in the mechanisms of tumor immune evasion. To block PD-Ls-PD-1
      interactions by a soluble receptor of PD-1, we constructed a eukaryotic
      expression plasmid that expresses extracellular region (aa1-aa167) of murine PD-1
      (pPD-1A) and, another version of pPD-1A, pPD-1B, carrying cDNAs encoding for both
      extracellular region of PD-1 and green fluorescent protein (GFP) reporter gene,
      which was inserted downstream of PD-1. Experiment of BHK cells transfected with
      pPD-1B determined that most expression product (sPD-1) in the cells was secreted
      out. FACS analysis revealed that sPD-1 was specific and bound efficiently to PD-1
      ligands. Cytotoxicity assay showed that blocking PD-Ls on either tumor cells or
      spleen cells by sPD-1 mediated enhanced lysis of H22 cells by Hsp70-H22 peptides
      complexstimulated spleen cells. The constructed plasmid vector would provide a
      novel method of tumor gene therapy of blocking PD-Ls-PD-1 interactions by
      expression of soluble receptor of PD-1 in tumor sites, which could increase the
      antitumor activity.

PMID- 15973994
TI  - [Integration of different T-DNA structures of ACC oxidase gene into carnation
      genome extended cut flower vase-life differently].
AB  - The cultivar 'Master' of carnation (Dianthus caryophyllus L.) was transformed
      with four T-DNA structures containing sense, antisense, sense direct repeat and
      antisense direct repeat gene of ACC oxidase mediated by Agrobacterium
      tumefaciens. Southern blotting detection showed that foreign gene was integrated
      into the carnation genome and 14 transgenic lines were obtained. The transgenic
      plants were transplanted to soil and grew normally in greenhouse. Of the 12
      transgenic lines screened, the cut flower vase life of 8 transgenic lines is up
      to 11 days and the longest one is 12.8 days while the vase life of the control is
      5.8 days under 25 degrees C. The vase life of 2 lines out of 3 with single sense
      ACO gene is same as that of the control, while the vase life of 3 lines out of 4
      with single antisense ACO gene is prolonged. The vase life of cut flowers of 5
      lines with direct repeat ACO genes is all prolonged by about 6 days, while the
      vase life of 3 out of 7 lines with single ACO gene is same as that of the
      control. During the senescence of cut flowers, the ethylene production of the
      most of the transgenic lines decreased significantly, and the production of
      ethylene is not detectable in lines T456, T556 and T575. The results of the
      research demonstrate that antisense foreign gene inhibits expression of
      endogenesis gene more significantly than sense one. Both sense direct repeat and
      antisense direct repeat foreign genes can suppress endogenous gene expression
      more significantly comparing to single foreign genes. The transgenic lines
      obtained from this research are useful to minimize carnation cut flower
      transportation and storage expenses.

PMID- 15973995
TI  - [Marker-assisted selection and pyramiding for three blast resistance genes, Pi
      d(t)1, Pi-b, Pi-ta2, in rice].
AB  - G46B is a promising holding line used for three-lines breeding strategy in hybrid
      rice, but it is susceptible to blast disease caused by Pyricularia grisea. To
      improve its blast resistance, three rice varieties, Digu, BL-1, and Pi-4, with
      blast resistance genes, Pi-d(t), Pi-b, and Pi-ta2, respectively, were used to be
      crossed with G46B, and 15 plants with these three blast resistance genes, Pi
      d(t)1, Pi-b, and Pi-ta2, were selected from their F2 and B1C1 populations via a
      marker-aided crossing procedure. Among them, four plants were heterozygotes in
      the three resistance genes, with the genotype of Pi-d(t)1 pi-d(t)/Pi-b pi-b/ Pi
      ta2 pi-ta2; ten plants were heterozygotes in two of the three resistance genes,
      of which six with the genotype of Pi-d(t)1 Pi-d(t)1/Pi-b pi-b/Pi-ta2 pi-ta2,
      three with the genotype of Pi-d(t)1 pi-d(t)1/Pi-b pi-b/Pi-ta2 Pi-ta2, and one
      with the genotype of Pi-d(t)1pi-d(t)1/Pi-b Pi-b/Pi-ta2 pi-ta2; and only one plant
      was homozygote in two of the three resistance genes with the genotype of Pi-d(t)1
      Pi-d(t)/Pi-b pi-b/Pi-ta2 Pi-ta2. These results demonstrate the capacity of maker
      assisted selection (MAS) in gene pyramiding for rice blast resistance and its
      enhancement for the efficiency in rice resistance breeding.

PMID- 15973996
TI  - Betaine improves LA-PCR amplification.
AB  - PCR is a powerful tool for the amplification of genetic sequences. It has been
      widely applied in molecular biology. It is generally used to amplify short
      segments (several hundreds basepairs to several kilobasepairs). It is difficult
      to amplify a long DNA segment. Based on the sequenced genes, it is known that
      most intact genes are very long. And intact gene is very important for the gene
      to express specially and effectively. Long PCR is a very useful tool to amplify
      intact genes for constructing special expression vectors. We have tried several
      chemicals to optimize long PCR system and found betaine was the best. Betaine, as
      an amino acid analogue with small tetraalkylammonium ions, could remarkably
      improve the amplification of long targets from the plant genome. The suitable
      concentration of betaine was between 1.0 mol/L and 2.5mol/L. We could effectively
      amplify a 9 kb DNA segment from maize genome DNA and a 16 kb DNA segment from
      plasmid. It was shown that different primers and different targets (different GC
      content) needed different concentrations of betaine. Betaine can reduce or
      eliminate non-special amplification. In the meantime we tried other additive
      chemicals, such as DMSO, glycerin, formamide. They were no notable results in
      long PCR.

PMID- 15973997
TI  - [Research on construction and biological characteristics of Actinobacillus
      pleuropneumoniae apxIIC mutant strain lacking drug resistance marker].

PMID- 15973998
TI  - [Cloning and function analysis of L-lactate dehydrogenase gene from Lactobacillus
      sp. MD-1].
AB  - It was constructed that a genomic DNA library from Lactobacillus sp. MD-1
      yielding D, L-lactic acid. The gene encoding L-lactate dehydrogenase (L-LDH) was
      cloned from the genomic library of strain MD-1 by complementation in E. coli
      FMJ144 which was lactate dehydrogenase and pyruvate-formate lyase double
      defective mutant. The nucleotide sequence of the ldhL gene predicted a protein of
      316 amino acid starting with ATG. The putative molecular weight of the L-LDH
      amino acid sequence was 33.84kD. A putative typical promoter (-35 and -10 boxes)
      had been observed in the 5' noncoding region. An rho-independent transcriptional
      terminator has been observed in the 3' noncoding region. Three highly conserved
      regions (Gly13 approximately Asp50, Asp73 approximately Ileul00 and Asn123
      approximately Arg154) with several conserved residues had been identified. Gly13
      approximately Asp50 was NADH-binding site domain. Asp73 approximately Ileu100 and
      Asn123 approximately Arg154 were reported to be the active site domains. The ldhL
      and the L-LDH of Lactobacillus sp. MD-1 showed the low identity and similarity
      with other Lactobacilli, and the highest percentage were 61.9% and 68.9%
      respectively. All the above indicated this gene is a novel ldhL.

PMID- 15973999
TI  - [Expression of Vitreoscilla hemoglobin and nitrilase in the yeast Pichia
      pastoris].
AB  - The expression of the vgb gene in vivo could improve the fermentation density and
      then contribute the extracellular secretion of the product of bxn gene.
      Constructed the recombination plasmid pPIC9K-vgbbxn and transformed into Pichia
      pastoris GS115. The results of PCR and SDS-PAGE indicate that the vgb gene and
      bxn gene had integrated into the genome of Pichia pastoris GS115 and expressed in
      efficient level. Also, the protein activity of their products had been verified
      respectively. Shake flask fermentation experiments showed that the presence of
      VHb in yeast Pichia pastoris efficiently enhanced cell growth and secretive
      expression of bxn gene under hypoxic habitats.

PMID- 15974000
TI  - [Constitutive expression and purification of Alcaligenes faecalis penicillin G
      acylase in Escherichia coli].
AB  - Considering Alcaligenes faecalis pencillin G acylase(AfPGA), which possesses the
      attractive characteristics for beta-lactam antibiotics conversions, the gene of
      PGA was cloned into an expressing vector pKKFPGA. The recombinant plasmid
      contained multicopy replicon(COLE 1), trc promoter, AfPGA gene, rrnB transcript
      terminator and ampicillin marker transformed Escherichia coli DH5alpha. As both
      the recombinant plasmid and the host DH5alpha had no laclq gene, the trc promoter
      was always active and the AfPGA could be constitutively expressed without IPTG
      induction in the host DH5alpha. In the shaking flask, the recombinant cell was
      inoculated into the fermentation medium (tryptone 10g/L, yeast extract 5g/L,
      MgSO4 x 7 H2O 1g, KH2 PO4 2g/L, K2HPO4 x 3H2O 5g/L, Na2HPO4 x 12H2O 7g/L,
      (NH4)2SO4 1.2g/L, NH4Cl 0.2 g/L, NaCl 0.1g/L, dextrin 30g/L) and cultured at 28
      degrees C for 20h. The production of AfPGA reached 2,590u/L(NIPAB method), with a
      cell-density-specific activity of more than 300(u/L)/A600, this yield increased
      432 fold higher than the native expression of Alcaligenes faecalis . Without
      ammonium sulphate fractionation and dialysis, the supernatant of crude extract
      was directly loaded on DEAE-Sepharose CL 6B column equilibrated by phosphate
      buffer (50mmol/L, pH7.8), and the enzyme fraction was not absorbed on the column
      but impurities were absorbed. Subsequently the effluent was added ammonium
      sulphate to 1mol/L and loaded on Butyl-Sepharose CL 4B column equilibrated by
      50mmol/L phosphate buffer pH7.8-1mol/L ammonium sulphate. The enzyme was eluted
      as concentration of ammonium sulphate in phosphate buffer decreased to 0, PGA was
      eluted. After these two column chromatography, the enzyme was enriched 20 times
      with a 91% activity recovery. The purified enzyme had a specific activity of
      68.6u/mg protein. However, the overproduction of PGA was often limited by
      translocation and/or periplasmic processing steps, subsequently resulted in
      intracellular accumulation of various types of PGA precursors and then formed
      inclusion bodies in the cytoplasm and/or periplasm. In this study, 5% PGA
      precursors formed as inclusion bodies in the cytoplasm while no inclusion bodies
      formed in the periplasm. It suggested most PGA precursors were transported to the
      periplasm and matured to active PGA and also explained why PGA gene was highly
      expressed in the host DH5alpha. On the other hand, inclusion bodies in the
      cytoplasm indicated that the maturation of PGA in the host DHSalpha was limited
      by the translocation step.

PMID- 15974001
TI  - [Expression, purification and enzymatic characterization of Bacillus polymyxa
      beta-glucosidase gene( bglA ) in Escherichia coli].
AB  - The beta-glucosidase encoding gene bglA was cloned from Bacillus polymyxa 1.794.
      The bglA gene was inserted in expression vector pET28a(+) and transformed into
      Escherichia coli BL21 (DE3), finally the recombinant strain BL1979 was obtained.
      Induced by IPTG, the expression P-glucosidase activity reached to 24.7 IU/mL. The
      optimum temperature and optimum pH of the recombinant expression P-glucosidase in
      BL1979 were 37 degrees C and 7.0 respectively,the purity can reach to 92.7%.
      Analysis of the fusion protein by nondenaturing gradient gel electrophoresis, we
      found the fusion protein exists in dimmer, tetramer,hexamer and octamer, they all
      have hydrolase activity.

PMID- 15974002
TI  - [Construction of CHO-IVB, A serum-independent, apoptosis-resistant cell line that
      can grow in adherence].
AB  - Without serum to provide adherent factors, CHO-dhfr- cells grow in suspension
      when cultured in serum-free medium. Although this offers advantages in some
      applications, in most production systems adherent cell growth is preferable. Gene
      transfection, clonal selection and amplification can be easier for adherent
      cells; the density of immobilized cells is often higher than those in suspension
      culture, which results in a higher protein productivity; washout of cells by
      perfused medium during continuous fermentation can be avoided; for high
      throughput microplate assays, adherent cells are preferred to facilitate medium
      changes and cell washing. It has been proved that purified vitronectin alone was
      able to mediate attachment and spreading of CHO cells in serum-free medium. So we
      constructed a tricistronic expression vector expressing Igf-1, Vitronectin and
      Bel-2 at the same time. The vector was transfected into CHO-dhfr- cells and one
      clone, namely CHO-IVB2, expressing high level of the three proteins was screened
      out by Western blot. The cell line showed similar apoptosis-resistant and serum
      independent properties to CHO-IB, an engineered cell line constructed before.
      When cultured in IMEM protein-free medium without any components supplemented,
      CHO-IVB can grow adherently. The viable cell numbers and growth rate of CHO-IVB
      were much higher than CHO-IB, making CHO-IVB an apoptosis-resistant host for
      production of recombinant proteins which can grow adherently in protein-free
      medium.

PMID- 15974003
TI  - [Screening of proteins interacting with Dishevelled2 in mouse 11.5dpc embryo
      library].
AB  - Dishevelled proteins are multifunctional and highly conserved. These proteins are
      also required for the specification of cell fate and polarity by secreted Wnt
      proteins. To investigate the molecular mechanism of Dishevelled in mediating Wnt
      signal transduction, a mouse 11.5dpc embryo library was screened by yeast-two
      hybrid system to find mouse Dishevelled2 DEP domain and C-terminal interacting
      proteins. 15 possitive clones were identified from 4.1 x 10(6) transformants. The
      DNA sequences of the positive AD/library plasmids were determined. The BLAST
      results revealed that one of the positive clones contained N-terminus cDNA
      fragments (amino acids 6-122) of Gli3 protein. The interaction between Dv12 and
      Gli3 detected by yeast two-hybrid system suggests that Gli3 might play a role in
      some biological processes with Dishevelled.

PMID- 15974004
TI  - [Biochemical stimulus effects in cell cleavage].
AB  - A lot of experimental findings have confirmed that: Animal cells acquire a
      spherical shape just before the division; Under biochemical stimulus of mitotic
      apparatus aster the cells form a contractile ring in equator plane, and the
      mother cell divides into two daughter cells; meanwhile the total volume keeps
      constant. In Zinemanas and Nir's model the reorientation of microfilament and the
      visco-elasticity of cortex have been took into consideration. In our present
      work, the effective coefficient m due to biochemical stimulus was incorporated
      into the model, and the local distribution C was modified to diffuse with the
      plasma membrane motion. The numerical results showed that the formation of a
      contractile ring and parameters such as the surface tension in the furrow and
      internal pressure can be predicted successfully. Compared with Zinemanas and
      Nir's model, the results of our model are more correspondent with the
      experimental results. It can be concluded that the effective coefficient m has
      limited effects on the process control of cytokinesis.

PMID- 15974005
TI  - [Optimization for isoflavone production in Maackia amurensis suspension cells
      based on neural networks and accelerating genetic algorithm].
AB  - The medium for isoflavone production in Maackia amurensis suspension cells has
      been optiwised through the artificial neural networks (ANNs) and the real coding
      based accelerating genetic algorithm (RAGA). Among the ingredients of the medium,
      nitrogen sources and plant growth regulators were found to be the main factors
      affecting the production of isoflavone genistein. (NH4)2SO4, KNO3, 2,4-D and 6
      BA, 100 approximately 800 mg/L, 1500 approximately 3000 mg/L, 0 approximately 3
      mg/L and 0 approximately 1 mg/L respectively, significantly increased genistein
      yield, in the ranges of effective concentrations. The random ten combinations of
      these four components generated by RAGA as input data and the genistein yields of
      ten combinations as output data were used for ANNs-RAGA (the artificial neural
      networks associated with the accelerating genetic algorithm) modeling. The
      resultant model showed a high fit between the experimental data and calculating
      values by ANNs-RAGA. Based on the prediction of the model, the optimum
      combination of four factors for genistein production was determined on 149.68
      mg/L for (NH4)2SO4, 2936.10 mg/L KNO3, 0.01 mg/L 2,4-D and 0.19 mg/L 6-BA. When
      cells were cultured in the optimized medium, their capability of genistein
      production was remarkably enhanced to 14.13 mg/L, which was about 19 times higher
      than that in the original medium. The relative discrepancy between the
      experimental value and the predictive value of genistein yield from the optimized
      medium was 7.38%.

PMID- 15974006
TI  - [Cloning and expression of xyn III from genomic DNA of Trichoderma reesei QM9414
      by overlap-PCR].
AB  - After the cell enters into its programmed cell death, xylanases from grass plants
      gradually matured through its N-terminal and C-terminal sequence been cut by acid
      proteases several times. They could not be expressed by conventional protein
      expression system. Search the GenBank database, xynIII from a mutant of T. reesei
      QM9414(ATCC26921)was found. It is similar to grass plants' xylanase in their
      families and structures. It couldn't express in T. reesei QM9414, but its gene
      exist in genomic DNA as one copy. Through overlap-PCR method, 4 exons of xynIII
      were cloned, sequenced, spliced, and the whole cDNA of mature xynIII was
      acquired. The cDNA was inserted into pETBlue-2 vector and transformed into E.
      coli DE3 pLacI cell. Xyn III could be expressed in the transformed cell under the
      conditions of 37 degrees C, 1 mmol/L IPTG induced for 3h. Low temperature (15
      degrees C), long time(64h) induction(0.2 mmol/L IPTG) could enhance xynIII
      activity.

PMID- 15974007
TI  - [Effect of supercritical CO2 to cellulase reaction].
AB  - The effects of pretreatment of supercritical carbon dioxide (SC-CO2) on the
      supramolecular structure of cellulose and the cellulase catalyzed reaction were
      investigated. The cellulase activity was not affected when it was treated with SC
      CO2 at 10MPa and at 50 degrees C for 30 min. But when the cellulase was treated
      by SC-CO2 in the presence of cellulose, the catalytic activity of the cellulase
      was lost. The cellulose pretreated with or without cellulase under the same SC
      CO2 condition was then hydrolyzed with tresh crude cellulase. The final reducing
      sugar yield from the hydrolysis of the cellulose pretreated with cellulase was
      higher than that of the cellulose pretreated without cellulase. It was also found
      that the improvement of the enzymolysis had a direct relevance with the amount of
      cellulase used during the SC-CO2 pretreatment. The moisture content of cellulose
      before SC-CO2 pretreatment had an obvious influence on the subsequent
      enzymolysis. When the moisture content of cellulose was 60% (W/W), the reducing
      sugar yield was higher than when the moisture content was over 100% (W/W). The FT
      IR spectra showed that the structure of the cellulose pretreated with cellulase
      under the SC-CO2 condition was different from that of the cellulose pretreated
      without cellulase. In the presence of the enzyme, the strength of the hydrogen
      bonds and the I beta phase at 710cm(-1) in the crystalline cellulose was
      weakened. These results suggest that the change in the cellulose structure
      induced by the SC-CO2 treatment favous the subsequent enzymolysis.

PMID- 15974008
TI  - Bacterial reduction of toxic Cr (VI) into Cr (III).
AB  - Two chromium-resistant bacterial strains CrT-1 and CrT-13, which can tolerate
      K2CrO4 up to 40 mg x mL(-1) on nutrient agar, 25 mg x mL(-1) K2 CrO4 in nutrient
      broth, and up to 10 mg x mL(-1) in acetate-minimal media, were used in this
      study. On the basis of 16S rRNA, strain CrT-1 was identified as Ochrobactrum
      intermedium and CrT-13 as Brevibacterium sp.. Uptake of chromate was greater in
      living cells than in heat-killed cells. Ochrobactrum intermedium CrT-1 reduced
      73% and 41% of Cr(V) while Brevibacterium CrT-13 reduced 62% and 48% Cr(VI) at an
      initial chromate concentration of 750, and 1500 microg x mL(-1), after 96 hours
      with an inoculum size of 9.6 x 10(7) cells mL(-1). Different heavy metals at low
      concentrations did not affect the reduction potential of the strains
      significantly. Ochrobactrum intermedium CrT-1 reduced 84% and 65% while
      Brevibacterium CrT-13 reduced 60% and 44% of Cr(VI) at an initial Cr(VI)
      concentration of 250 and 500 microg x mL(-1), respectively, in an industrial
      effluent sample.

PMID- 15974009
TI  - [Studies on synthesis of polyhydroxyalkanoate consisting of 3-hydroxyvalerate by
      Aeromonas hydrophila].
AB  - Polyhydroxyalkanoates (PHA) is a family of microbially synthesized polyesters
      consisting of various 3-hydroxyalkanoate monomers. Aeromonas hydrophila 4AK4
      could be able to synthesize PHA copolymer consisting of 3-hydroxybutyrate (3-HB)
      and 3-hydroxyhexanoate (3-HHx). No data has been reported about the ability to
      synthesize the PHA with other monomers in A. hydrophila. In this study, propionic
      acid, valeric acid, heptanoic acid, nonanoic acid and undecanoic acid were used
      together with gluconate to find out whether A. hydrophila 4AK4 could synthesize
      the PHA consisting of odd carbon atom number monomers. The result showed that A.
      hydrophila 4AK4 could not growth when supplied with propionic acid, valeric acid,
      heptanoic acid and nonanoic acid and only undecanoic acid could be used to
      synthesize PHA. Wild type and recombinant A. hydrophila 4AK4 harboring phaA (beta
      ketothiolase) and phaB (acetoacetyl-CoA reductase) were cultivated with
      undecanoic acid and glucose or undecanoic acid and gluconate served as carbon
      sources. PHA consisting of 3-HB and 3-hydroxyvalerate (3-HV) could be produced by
      both wild type and recombinant A. hydrophila 4AK4 and the latter could produce
      PHA with more 3-HB monomer. When the ratio of glucose or gluconate to undecanoic
      acid was 1:1, the cell dry weight (CDW) of A. hydrophila 4AK4 reached 1.14 g/L
      and PHA content was 60% of the CDW after cultivation for 24 h. When lauric acid
      and undecanoic acid were served as co-substrate, A. hydrophila 4AK4 could produce
      copolyester consisting of 3-HB, 3-HV and 3-HHx. Along with the increase of
      undecanoic acid proportion in the mixed carbon source, the 3-HV content of
      copolymer was increased while the 3-HB and 3-HHx content were decreased. In all
      cases, the CDW decreased along with the increase of undecanoic acid
      concentration, which indicated that undecanoic acid was not very good for A.
      hydrophila 4AK4 growth.

PMID- 15974010
TI  - Influence of phospholipid fatty acid composition of plasma membrane on
      sensitivity of plasma membrane ATPase of a self-flocculating yeast to in vivo
      ethanol activation and its relationship to ethanol tolerance.
AB  - Although alterations in fatty acid composition of phospholipids in plasma
      membranes had no effect on activities of plasma membrane ATPases of a self
      flocculating fusant of Schizosaccharomyces pombe and Saccharomyces cerevisiae
      cells grown in the absence of ethanol (basal enzymes), they significantly
      affected the susceptibilities of the enzymes to in vivo activation induced by
      ethanol: the maximal values for the activated enzymes in cells pregrown with 0.6
      mmol/L palmitic, linoleic or linolenic acid respectively were 3.6, 1.5 and 1.2
      fold higher than their respective basal levels (in cells grown without ethanol),
      whereas the corresponding value for cells pregrown in the absence of fatty acid
      was 2.3-fold, with the concentrations of ethanol for the above maximal in vivo
      activation of enzymes being 7%, 6%, 6% and 7% (V/V) respectively. The Km values
      for ATP, the pH profiles, and the sensitivities to orthovanadate of the basal and
      the activated plasma membrane ATPases were essentially identical; however, the
      v(max) values of activated enzymes increased significantly. It was found that the
      characteristics of phospholipid fatty acid composition of plasma membrane leading
      to the enhanced ethanol tolerance of this strain, were also efficacious to
      increase the percentage of activation of plasma membrane ATPase per unit of
      ethanol. These data support a close correlation between the ethanol tolerance of
      this strain and the sensitivity of its plasma membrane ATPase to the in vivo
      ethanol-induced activation.

PMID- 15974011
TI  - [Polylactic acid nanoparticles across the brain-blood barrier observed with
      analytical electron microscopy].
AB  - The blood-brain barrier (BBB) is a huge obstacle in therapy of brain diseases,
      for it hinders the delivery of water-soluble molecules and those with molecular
      weight above 500 from the circulation system to the brain. Polysorbate 80 (Tween
      80, T-80)-coated polylactid acid(PLA) nanoparticles represent a tool to transport
      such drugs across the BBB. Transcytosis is put forward as one mechanism of drug
      loaded nanoparticles across the blood-brain barrier (BBB). However little is
      known about it. Electron microscopy is an important method in the investigation
      on nanoparticles injected into the experimental mice. In this study it was found
      by fluorescence microscope that fluorescence existed along the capillary
      dissepiment. Some nanoparticles distributed in the brain capillary endothelial
      cells and brain tissue outside the microvaculum, which was observed by
      transmission electron microscopy. These particles were proved to be the Copper
      chlorophyll loaded nanoparticles which containing Cu detected by AEM. The in vivo
      experiments demonstrated directly that the PLA nanoparticles can pass the BBB
      indeed and transcytosis by microvascular endothelial cells may be the mechanism.
      The results provided an efficient way of drug-delivery targeting the brain.
      Copper chlorophyll could be used as a new symbol of nanoparticles in in vivo
      experiment.

PMID- 15974012
TI  - [Research on critical aerating flux of internal-loop granular sludge bed
      nitrifying reactor].
AB  - The internal-loop granular sludge bed nitrifying reactor is a new type of aerobic
      nitrifying equipment and has taken on a good potential for nitrification. The
      critical aerating flux for liquid loop and critical aerating flux for
      fluidization of granular sludge are two important parameters for its operation.
      The relationship between liquid superficial velocity in riser (U1r) and aerating
      flux(Ugr) was studied, the model parameters were measured by experiment, and the
      relational expression was established. According to the model, the critical
      aerating flux for liquid loop and the critical aerating flux for fluidization of
      granular sludge were calculated as 1.017cm/min and 2.662cm/min, respectively. The
      experimental data from reactor operation showed that the two calculated critical
      aerating fluxes near the practical values. So they could be used to direct the
      design and operating optimization for the internal-loop granular sludge bed
      nitrifying reactor.

PMID- 15974013
TI  - [Production of recombinant humanized anti-HBsAg Fab antibody by fermentation].
AB  - In order to produce recombinant human anti-HBsAg Fab antibody in Pichia pastoris,
      the recombinant yeast was fermented using fed-batch system in a 30 L bioreactor.
      The fermentation temperature was 30 degrees C, the pH was 5.0 approximately 5.3,
      and the DO was 20% approximately 30%. The recombinant Fab antibody was purified
      from crude culture supernatant by ion exchange and analyzed by SDS-PAGE and
      western blot and ELISA. When the absorbance (OD600) of broth reach 300 at the end
      of fed-batch phase, the induced phase was initiated. The results showed that
      recombinant human anti-HBsAg Fab antibody was high-level expressed in recombinant
      Pichia pastoris using a fed-batch fermentation system. Both chains of the Fab
      were successfully expressed upon methanol induction. After 192 h of induction,
      the expression level of recombinant Fab (soluble) reached 412 mg/L. The
      recombinant Fab antibody was purified effectively by ion-exchange chromatography
      from the fermentation supernatant to a purity of 95%. And the affinity activities
      of the purified recombinant Fab antibdy and fermentation supernatant were
      detected, and both of them showed high affinity activities. The results
      demonstrated that recombinant human anti-HBsAg Fab antibody could be high level
      produced by fed-batch fermentations in Pichia pastoris. Which can be efficiently
      used in industrial production.

PMID- 15974014
TI  - Do we really know what nurses want?

PMID- 15974015
TI  - [Cross-cultural study on loneliness of students at the University of the Free
      State].
AB  - Many young people today are lonely and hopeless, and feel that life has no
      meaning. The existing literature indicates that this phenomenon is taking on near
      epidemic proportions in industrialised Western countries. A considerable amount
      of cross-cultural investigations have already been conducted overseas between
      different population groups, in order to determine what the causes of this
      phenomenon are and whether culture plays an important role in the development of
      loneliness. As far as this type of research is concerned South Africa is
      currently far behind the rest of the world. Serious efforts shall have to be made
      to determine whether loneliness is taking on the same proportions locally and if
      certain population groups are more vulnerable than others, because it could have
      far-reaching consequences on their physical as well as psychological health.
      South Africa has a rich population variety which could enable researchers to
      investigate emotional constructs like loneliness that could contribute to the
      unravelling of this multifaceted phenomenon. The purpose of this investigation
      was therefore to determine whether students from different cultural backgrounds
      at the University of the Free State differ from each other, as far as their
      experience of loneliness is concerned. Questionnaires were distributed among
      students and 270 respondents, of which 122 were white and 148 black, took part in
      this study. A factorial analysis of variance was applied on the data, with
      loneliness as dependent variable, and cultural background, gender and age as
      independent variables. The results firstly show that cultural background is a
      very important variable as far as loneliness is concerned. Black students are
      significantly more lonely than white students while no gender and age differences
      between the groups were found.

PMID- 15974016
TI  - Spirituality in nursing: an analysis of the concept.
AB  - There is scientific evidence that the spiritual well being of a person can affect
      quality of life and the response to illness, pain, suffering and even death. In
      spite of this evidence, spirituality in nursing has not been examined within a
      South African context. The purpose of this study was to describe the phenomenon
      of spirituality from the perspective of nurses and patients/clients with the aim
      of generating a middle range theory of spiritual care in nursing. A qualitative
      mode of inquiry using a grounded theory method was applied. A sample of 56
      participants composed of 40 nurses, 14 patients and 2 relatives of patients was
      recruited by theoretical sampling procedure from one public hospital, one private
      hospital and one hospice setting. Focus group interviews and one on one in depth
      interviews were conducted. An audio tape recorder was used to record the
      interviews. Field notes and memos were also kept. Data were collected and
      analyzed simultaneously. Non numerical Data Qualification Solutions NUDIST
      software was used to code data into different levels of codes. The results were
      rich descriptions of the concept of spirituality. This concept was described as a
      unique individual quest for establishing and, or, maintaining a dynamic
      transcendent relationship with self, others and with God/supernatural being as
      understood by the person. Faith, trust and religious belief were reported as
      antecedents of spirituality, while hope, inner peace and meaningful life were
      reported to be consequences of spirituality.

PMID- 15974017
TI  - Indicators of substance abuse treatment demand in Cape Town, South Africa (1997
      2001).
AB  - Few studies have investigated the demand for substance abuse treatment in South
      Africa. This article uses data collected from specialist substance abuse
      treatment centres to describe substance abuse treatment demand and patterns of
      service utilisation in Cape Town for the period January 1997 to December 2001.
      Findings suggest that although treatment demand for alcohol-related problems
      remains high, treatment demand for substances other than alcohol has increased
      over time. Patterns of treatment service utilisation suggest that women and black
      South Africans remain underserved. The need for comprehensive and accessible
      substance abuse treatment services in Cape Town is highlighted and
      recommendations are made for improving access to treatment services, and
      undertaking comprehensive evaluations of existing treatment facilities.

PMID- 15974018
TI  - Severe disability: do primary health care nurses have a role to play?
AB  - This article focuses on the importance of primary health care nurses' involvement
      in the identification of children with severe disabilities, early and appropriate
      intervention that includes referral, as well as the provision of support to the
      children's caregivers. The use of multiskilling as a strategy to train nurses to
      fulfil this role is described. The traditional roles of community nurses are
      explored within the disability paradigm, with specific reference to multi
      skilling. Finally, research results following the implementation of the Beginning
      Communication Intervention Protocol (BCIP), which uses multi-skilling as a
      training strategy, are described. Recommendations for further research are then
      provided.

PMID- 15974019
TI  - The perceptions of nurses in a district health system in KwaZulu-Natal of their
      supervision, self-esteem and job satisfaction.
AB  - BACKGROUND: Supervision has been identified as a major issue in quality of care.
      Although increasing attention is being given to supervision in the District
      Health System, there have been no studies describing the current situation. This
      article describes a survey done in two health districts in KwaZulu-Natal
      involving 319 nurses from all types of government health care settings. METHODS:
      This was a quantitative descriptive study that described the current supervision,
      job satisfaction and self-esteem in two (2) health districts, that is the Ugu and
      the uThukela health districts. The three variables were described using a mailed
      questionnaire. A total 319 nurses participated in this study. RESULTS: The
      majority of the nurses (53%) felt that positive supervision behaviours listed in
      a rating scale, occurred never or seldom. The average self-esteem score was very
      positive (83%), and the average job satisfaction score was 60%. Nurses were most
      satisfied with the factor reflecting "personal satisfaction about their
      contribution to the work" (72%) and the least satisfaction with the factor that
      has to do with "pay and prospects" (50%). While there was no relationship between
      any of the demographic variables and supervision, there was a low but significant
      relationship between supervision and job-satisfaction. A significant relationship
      was also found between the personal satisfaction factor of job satisfaction and
      self-esteem. CONCLUSION: As nurses form the backbone of the health services, it
      is incumbent that health service managers safeguard the nursing workforce.
      Targeted strategies are necessary to ensure retention of the nurses for the
      health care of the South African population.

PMID- 15974020
TI  - Mortality and morbidity among traditionally circumcised Xhosa boys in the Eastern
      Cape Province, South Africa.
AB  - Male circumcision is one of the oldest traditions observed by many societies. The
      ritual is performed at specific periods in life with the main purpose of
      integrating the male child into the society according to cultural norms.
      Recently, especially in the Eastern Cape, many initiates have died or have had to
      face life with mutilated genitals following this ritual. THE OBJECTIVE: of the
      study was to explore the causes of morbidity and mortality among traditionally
      circumcised Xhosa boys in the Eastern Cape. METHODOLOGY: A revelatory case study
      design was used to obtain information from initiates and traditional surgeons and
      attendants in the Flagstaff District. RESULTS: From the data collected,
      restriction of fluid intake, unhealthy surroundings, like, cold and dusty holding
      rooms and incompetent attendants were cited as factors that contributed to
      dehydration; wound infection and respiratory infection. CONCLUSION: The initiates
      recommended a collaboration with the Department of Health to ensure that
      circumcision is performed by knowledgeable persons in appropriate surroundings
      i.e. a clean and warm room with adequate space.

PMID- 15974021
TI  - Nutrition related knowledge and practices of hypertensive adults attending
      hypertensive clinics at Day Hospitals in the Cape Metropole.
AB  - The aim of this study was to determine nutrition knowledge and dietary practices
      of hypertensive adults attending hypertensive clinics at Day Hospitals in the
      Cape Metropole. Ten Day Hospitals were randomly selected from a total of 31 Day
      Hospitals and the first participants attending the hypertension clinics per day
      were recruited. A total of 85 participants were evaluated. The weight, height,
      waist and hip circumference of each participant was measured, as well as their
      blood pressure. Knowledge of dietary intake was obtained by completing a
      questionnaire, during an interview with the patient. Knowledge regarding salt
      usage indicated that a large percentage (34.1%) of participants believed that
      flavour enhancers like Aromat or Fondor could safely be used instead of table
      salt. Furthermore, 23.5% reported that tinned and smoked meat or fish have a low
      sodium (salt) content. Fruit and vegetables were perceived as having a positive
      effect on hypertension by 74.1% of participants. However, only 15% of the group
      knew that the recommendation for their usage was five or more servings per day.
      Only 12.9% of participants in this study had a normal weight (body mass index
      (BMI) < 25), 25.9% were overweight (BMI 25 - 29.9) and 61.2% were obese (BMI > or
      =30); 84.7% recognized the association between obesity and hypertension. A large
      waist circumference (> 88 cm in women; 102 cm in men) was found in 61.2% of
      participants, however, only 18.2% of black men had such a measurement.
      Uncontrolled blood pressure readings (> 140/90 mm Hg) were found in 61.2% of
      these patients at the hypertension clinics.

PMID- 15974023
TI  - Would you eat a clone?

PMID- 15974022
TI  - Eat them or lose them.

PMID- 15974024
TI  - A shingles vaccine.

PMID- 15974025
TI  - A ripe old age. The right foods, moderate exercise, and regular medical checkups
      can add years to your life.

PMID- 15974026
TI  - Social planning. Seniors who fill up their calendars with a variety of activities
      are more likely to relish retirement. Interview by Kim Clark.

PMID- 15974027
TI  - Beating the odds. Finely tuned diagnoses and targeted drugs are creating optimism
      about surviving breast cancer.

PMID- 15974028
TI  - Hold the champagne.

PMID- 15974029
TI  - To protect the innocent. Learning to keep sexual predators at bay.

PMID- 15974030
TI  - Why we need nosy parkers. Busybodies, it turns out, may help us coexist.

PMID- 15974031
TI  - Therapy that gets inside your head--literally.

PMID- 15974032
TI  - Drug wars.

PMID- 15974033
TI  - Diagnosing for dollars.

PMID- 15974034
TI  - Credentialing cosmetic dentists--part II.

PMID- 15974035
TI  - Cardiovascular disease and the dental team.

PMID- 15974036
TI  - Achieving optimal aesthetics for direct and indirect restorations with
      microhybrid composite resins.
AB  - In aesthetic dentistry, material science has played a key role in the development
      of natural-appearing restorations. Despite the progress, there have been
      challenges in achieving a harmonious integration of direct and indirect posterior
      restorations. Although porcelain restorations provide natural aesthetics,
      ceramics cannot be applied via direct techniques. Consequently, composite resins
      are valuable alternatives for conservative posterior restorations. In addition,
      because of their differing physical and optical properties, optimal aesthetic
      blending with porcelain and resin cannot be routinely achieved. This article
      explores the potential of composite resins as a direct and indirect restorative
      option in achieving the most favorable natural blend in the posterior region.

PMID- 15974037
TI  - Moisture control and marginal access for aesthetic dentistry: a case report.

PMID- 15974038
TI  - The evolution of the preparation design.

PMID- 15974039
TI  - Indirect impression technique for multiple cast dowel and cores facilitated with
      three putty indexes.
AB  - Fabrication of multiple direct cast dowel-and-core patterns is time-consuming and
      difficult because the clinician must assess the adequacy of the reduction of the
      final restoration and the path of insertion for the patterns. This article
      describes a technique for making impressions of multiple endodontically treated
      teeth for the indirect fabrication of cast dowel and cores, which are waxed up
      via three putty indexes obtained from the diagnostic waxup. This enables
      clinicians and technicians to communicate in a manner that facilitates
      predictable and consistent prosthetic therapy.

PMID- 15974040
TI  - Endoimplantology: a paradigm shift in endodontic therapy.

PMID- 15974041
TI  - Layering and curing techniques for class III restorations: a two-year case
      report.
AB  - The direct resin buildup of a Class III restoration based on contemporary
      layering and curing techniques allows clinicians to provide conservative
      treatment and a virtually imperceptible blend with adjacent tooth structures.
      This presentation describes a new approach to the Class III buildup. The
      importance of restoring enamel and dentin as two different substrates is also
      stressed. In this context, the selection of a microhybrid composite resin system
      able to reproduce the optical and mechanical properties of the natural dentition
      can help to achieve these goals.

PMID- 15974042
TI  - Bonding to porcelain.

PMID- 15974043
TI  - Curing lawyers [April fool's].

PMID- 15974044
TI  - Oh death, where is thy definition?

PMID- 15974045
TI  - The early years of hospice care in Rhode Island.

PMID- 15974046
TI  - Rules to use and rules to lose for pain management in the long-term care setting.

PMID- 15974047
TI  - A pastoral perspective on death and those who survive.

PMID- 15974048
TI  - Barriers to hospice: access delayed, access denied.

PMID- 15974049
TI  - What is the Ocean State Ethics Network?

PMID- 15974050
TI  - Neurocysticercosis.

PMID- 15974051
TI  - Changes in sources of health care coverage in Rhode Island.

PMID- 15974052
TI  - Osteoporosis: missed opportunities for diagnosis and treatment in Rhode Island.

PMID- 15974053
TI  - Time stresses in the lives of physicians.

PMID- 15974054
TI  - The colorful words of medicine, part II.

PMID- 15974055
TI  - Systemic traumatic stress: the couple adaptation to traumatic stress model.
AB  - Research traditionally has focused on the development of symptoms in those who
      experienced trauma directly but overlooked the impact of trauma on the families
      of victims. In recent years, researchers and clinicians have begun to examine how
      individual exposure to traumatic stress affects the spouses/partners, children,
      and professional helpers of trauma survivors. However, empirically supported,
      theory-based literature that identifies the mechanisms by which interpersonal or
      "secondary trauma" occurs in response to traumatic events is limited. Here, we
      present the Couple Adaptation to Traumatic Stress Model, a systemic model of the
      development of interpersonal symptoms in the couple dyad based on empirical
      literature. Potential mechanisms and clinical vignettes are included to describe
      the systemic processes that occur with trauma couples. Areas for future research
      and clinical implications also are identified.

PMID- 15974056
TI  - Impact of marital and psychological distress on therapeutic alliance in couples
      undergoing couple therapy.
AB  - In this study, we describe the psychometric properties of the Couple Therapy
      Alliance Scale--revised (CTAS-r) and investigates the impact of marital and
      psychiatric distress on alliance. Seventy-nine couples in therapy completed a
      French version of the Dyadic Adjustment Scale and of the Psychiatric Symptoms
      Index at session one, and a French version of the CTAS-r at session three.
      Results indicate that the French version of the CTAS-r has adequate psychometric
      properties, although the subscales of the instrument are highly intercorrelated.
      Furthermore, marital adjustment predicts alliance scores, whereas psychiatric
      symptoms do not. Finally, male marital adjustment and female psychiatric symptoms
      are lower in couples where spouses have divergent perceptions of the alliance.
      Future research directions are discussed.

PMID- 15974057
TI  - Family and marital profiles of couples in which one partner has depression or
      anxiety.
AB  - Twenty-nine couples in which one partner was depressed, 21 couples in which one
      partner had an anxiety disorder, and 26 nondistressed control couples were
      compared on measures of (1) quality of life, stress, and social support; (2)
      family functioning; (3) marital functioning; and (4) relationship attributions.
      The depressed group had significant difficulties in all four domains. In
      contrast, the control group showed minimal difficulties. The profile of the
      anxious group occupied an intermediate position between those of the other two
      groups, with some difficulties in all four domains, although these were less
      severe and pervasive than those of the depressed group.

PMID- 15974058
TI  - Infidelity in committed relationships I: a methodological review.
AB  - Infidelity is perhaps the most complex issue encountered by couple therapists.
      Although clinical literature, opinion, and speculation on this topic are
      abundant, research literature is sparse. What little available research exists
      is, in most cases, neither robust nor helpful to the practicing therapist. This
      article provides, in both narrative and table format, a comprehensive
      methodological review of the available research literature on infidelity from
      1980 to present. Topics addressed in the narrative include the lack of a
      consensus on the definition of infidelity; design challenges, such as
      retrospective research, confidentiality, measures, and variables, and sampling
      issues, such as diversity and randomization. Throughout the article, we offer
      suggestions for future research.

PMID- 15974059
TI  - Infidelity in committed relationships II: a substantive review.
AB  - This article, a follow-up on our methodological review of infidelity studies,
      provides a substantive review of the research findings on infidelity in committed
      relationships. The aim of this article is to present the most conclusive findings
      available to both researcher and practitioner on the subject of infidelity. We
      highlight attitudes toward infidelity; prevalence data; types of infidelity;
      gender dynamics and infidelity; issues in the primary relationship and their
      relationship to infidelity; race, culture, and infidelity; education, income,
      employment, and infidelity; justifications for infidelity; individual issues and
      their relationship to infidelity; same-sex couples and infidelity; attachment and
      infidelity; opportunity and infidelity; the aftermath and recovery process from
      infidelity; and clinical practices.

PMID- 15974060
TI  - Moving beyond gender: processes that create relationship equality.
AB  - Equality is related to relationship success, yet few couples achieve it. In this
      qualitative study, we examine how couples with children in two time cohorts (1982
      and 2001) moved toward equality. The analysis identifies three types of couples:
      Postgender, gender legacy, and traditional. Movement toward equality is
      facilitated by: (a) Stimulus for change, including awareness of gender,
      commitment to family and work, and situational pressures; and (b) patterns that
      promote change, including active negotiation, challenges to gender entitlement,
      development of new competencies, and mutual attention to relationship and family
      tasks. Implications for practice are discussed.

PMID- 15974061
TI  - Adolescents coping with mom's breast cancer: developing family intervention
      programs.
AB  - The purpose of this pilot study was to gain a deeper understanding of how
      adolescents are affected by their mothers' breast cancer and to discover their
      opinions about how future intervention programs should be designed. Three focus
      groups were conducted with a total of 10 adolescents. Findings indicate that
      adolescents' lives had been complicated by their mothers' illness, as they often
      felt burdened with additional roles and responsibilities. Adolescents suggested
      that future intervention programs should have the following elements: Adolescent
      group comprised of boys and girls within 4 months of cancer diagnosis;
      psychoeducation; target coping skills sensitive to girls and boys of different
      ethnic and racial backgrounds; and after the adolescent groups, have multiple
      family therapy groups that promote shared family understanding and open
      communication between parents and adolescents.

PMID- 15974062
TI  - Function at the junction: revisiting the idea of functionality in family therapy.
AB  - With the emergence of postmodern models and critiques, the concept of symptom
      functionality has lost favor in the family therapy field. To be reconsidered as
      clinically valuable it must both demonstrate pragmatic utility and meet ethical
      and conceptual criteria. Functional hypotheses cannot be believed too strongly,
      used to blame, or employed without considerations of biology. Symptom
      functionality is considered in its strong and weak versions. Tempered by the more
      ecological weak sense, strong-sense functional hypotheses are presented as one
      form of description that can guide a therapist's actions.

PMID- 15974063
TI  - Optimisation of solvent desorption conditions for chemical warfare agent and
      simulant compounds from Porapak Q using experimental design. Part 2: Extraction
      of sulphur mustard from steel and glass Porapak tubes.
AB  - The vesicant chemical warfare (CW) agent sulphur mustard remains a hazard to
      personnel involved in demilitarisation activities. Sampling tubes containing
      Porapak Q are used to measure personal exposure to sulphur mustard vapour.
      Presented here is an evaluation of the solvent desorption parameters employed to
      remove sulphur mustard from steel and glass tubes containing Porapak Q.
      Statistical experimental design was used to elucidate the influence of solvent
      type, tube type, solvent volume and sonication time on sulphur mustard recovery.
      The order of increasing recovery was established as iso-octane < hexane =
      isopropyl alcohol. The same degree of sulphur mustard is recovered on both steel
      and glass tubes using hexane or isopropyl alcohol, with hexane exhibiting
      quantitative recovery. The sorbent mass (50 mg) should be increased when using
      steel tubes as breakthrough has been demonstrated. Given the inert nature of
      hexane towards sulphur mustard, its favourable chromatographic properties for
      splitless injection, and its greater recoveries, this solvent should be used for
      elution of Porapak Q tubes for quantitative analysis of sulphur mustard.

PMID- 15974064
TI  - Optimisation of a new headspace mass spectrometry instrument. Discrimination of
      different geographical origin olive oils.
AB  - A fast head-space analysis instrument, constituted by an automatic sample
      introduction system directly coupled to a mass detector without performing any
      chromatographic separation, was assembled. A suitable and original response was
      computed to optimise, by experimental design, the measured signals for
      discrimination purposes. The volatile fractions of 105 extra virgin olive oils
      coming from five different Mediterranean areas were analysed. The rough
      information collected by this system was unravelled and explained by well-known
      chemometrical techniques of display (principal component analysis), feature
      selection (stepwise linear discriminant analysis) and classification (linear
      discriminant analysis). The 93.4% of samples resulted to be correctly classified
      and the 90.5% correctly predicted by cross-validation procedure, whilst the 80.0%
      of an external test set, created to full validate the classification rule, were
      correctly assigned.

PMID- 15974065
TI  - Preparation and application of the sol-gel-derived acrylate/silicone co-polymer
      coatings for headspace solid-phase microextraction of 2-chloroethyl ethyl sulfide
      in soil.
AB  - Three types of novel acrylate/silicone co-polymer coatings, including co
      poly(methyl acrylate/hydroxy-terminated silicone oil) (MA/OH-TSO), co-poly(methyl
      methacrylate/OH-TSO) (MMA/OH-TSO) and co-poly(butyl methacrylate/OH-TSO) (BMA/OH
      TSO), were prepared for the first time by sol-gel method and cross-linking
      technology and subsequently applied to headspace solid-phase microextraction (HS
      SPME) of 2-chloroethyl ethyl sulfide (CEES), a surrogate of mustard, in soil. The
      underlying mechanisms of the coating process were discussed and confirmed by IR
      spectra. The selectivity of the three types of sol-gel-derived acrylate/silicone
      coated fibers was studied, and the BMA/OH-TSO coated fibers exhibited the highest
      extraction ability to CEES. The concentration of BMA and OH-TSO in sol solution
      was optimized, and the BMA/OH-TSO (3:1)-coated fibers possessed the highest
      extraction efficiency. Compared with commercially available polyacrylate (PA)
      fiber, the sol-gel-derived BMA/OH-TSO (3:1) fibers showed much higher extraction
      efficiency to CEES. Therefore, the BMA/OH-TSO (3:1)-coated fibers were chosen for
      the analysis of CEES in soil matrix. The reproducibility of coating preparation
      was satisfactory, with the RSD 2.39% within batch and 3.52% between batches,
      respectively. The coatings proved to be quite stable at high temperature (to 350
      degrees C) and in different solvents (organic or inorganic), thus their lifetimes
      (to 150 times) are longer than conventional fibers. Extraction parameters, such
      as the volume of water added to the soil, extraction temperature and time, and
      the ionic strength were optimized. The linearity was from 0.1 to 10 microg/g, the
      limit of detection (LOD) was 2.7 ng/g, and the RSD was 2.19%. The recovery of
      CEES was 88.06% in agriculture soil, 92.61% in red clay, and 101.95% in sandy
      soil, respectively.

PMID- 15974066
TI  - On-matrix derivatisation-extraction of precursors of nitrogen- and sulfur
      mustards for verification of chemical weapons convention.
AB  - Development and refinement of sample preparation protocols for retrospective
      detection and identification of chemical warfare agents (CWAs) and their markers
      is of paramount importance from verification point of view of chemical weapons
      convention (CWC). Precursors of nitrogen- and sulfur-mustards (NMPs and SMPs) are
      polar adsorptive markers of vesicant class of CWAs. Their detection in a given
      environmental sample may imply past contamination with mustards. For the
      efficient extraction of NMPs and SMPs from soil, on-matrix derivatisation
      extraction (OMDEX) method was developed and optimized. The method involved
      trifluoroacetylation of analytes on soil itself, followed by extraction with
      suitable solvent. The extracted samples were analyzed by gas chromatography-mass
      spectrometry (GC-MS). This virtually single-step sample preparation offered
      better recoveries of NMPs and SMPs in comparison to conventionally used
      extraction, evaporation and derivatisation. The best recoveries of analytes were
      obtained with acetonitrile by OMDEX method. Dynamic linearity range of
      trifluoroacetylated (TFA) derivatives of NMPs and SMPs was 1-12 microg/L in GC-MS
      analysis in SIM mode. Repeatability and reproducibility of this technique
      containing 5 and 10 microg analytes/gm soil was <3.3% and <4.6%, respectively.
      OMDEX technique was finally applied for the detection of TFA derivatives of NMPs
      in the soil sample supplied in 16th official proficiency test conducted by OPCW
      in October 2004.

PMID- 15974067
TI  - Evaluation of ethoxynonafluorobutane as a safe and environmentally friendly
      solvent for chiral normal-phase LC-atmospheric pressure chemical
      ionization/electrospray ionization-mass spectrometry.
AB  - Coupling normal-phase LC separation methods to atmospheric pressure ionization
      (API)-mass spectrometry (MS) for detection can be problematic because of the
      possible detonation hazard and because nonpolar solvents do not support
      ionization of the analyte. Unlike achiral separations, enantiomeric separations
      can be very sensitive to small changes in the separation environment. Thus,
      completely substituting the main mobile phase component of a normal-phase LC
      solvent for an environmentally friendly, nonflammable fluorocarbon-ether as a
      safe and effective solvent must be thoroughly evaluated before it can be
      recommended for enantioselective separations with API-MS detection.
      Ethoxynonafluorobutane (ENFB) was used as a normal-phase solvent for the
      enantioselective separation of 15 compounds on two macrocyclic glycopeptide
      chiral stationary phases (CSPs) and a new polymeric chiral stationary phase. The
      chromatographic figures of merit were compared between results obtained with the
      ENFB mobile phases and traditional heptane-based mobile phases. In addition, the
      limits of detection (LOD) using the API-MS compatible ENFB were examined, as well
      as flow rate sensitivities and compatibilities with common polar organic
      modifier. ENFB is a safe and effective solvent for enantioselective normal
      phase/API-MS analyses.

PMID- 15974068
TI  - Identification of lipid binders in old oil paintings by separation of 4
      bromomethyl-7-methoxycoumarin derivatives of fatty acids by liquid chromatography
      with fluorescence detection.
AB  - A HPLC-fluorescence method for identification of drying oils from binding media
      or protective film used in pictorial works of art prior to conservation or
      restoration is proposed. Fluorescence derivatization of fatty acids released by
      hydrolysis of structural drying oils is studied. The derivatization reagent was 4
      (bromomethyl)-7-methoxycoumarin with 18-crown-6 as catalyst. Mobile phase was
      programmed from methanol-water (90:10 v/v) to methanol-water (100:0 v/v) in 25
      min. The excitation and emission wavelengths were 325 and 395 nm, respectively.
      Under these chromatographic conditions, coumarin derivatives of myristic,
      palmitic, oleic and stearic acids were satisfactorily resolved. The method shows
      good sensitivity, with a detection limit of 6.0 x 10(-8) mmol, and good linearity
      between 1.0 x 10(-7) and 1.8 x 10(-4) mmol of each analyte. Peak area ratios
      among fatty acids derivatives, especially the stearic acid/palmitic acid peak
      area ratio, are useful to identify the drying oils. The proposed method has been
      successfully applied to artistic samples from items of the cultural heritage of
      Valencia (Spain).

PMID- 15974069
TI  - Comprehensive two-dimensional liquid chromatography for the characterization of
      functional acrylate polymers.
AB  - Comprehensive two-dimensional liquid chromatography-size-exclusion chromatography
      (LC x SEC) was investigated as a tool for the characterization of functional
      poly(methyl methacrylate) (PMMA) polymers. Ultraviolet-absorbance and evaporative
      light-scattering detection (ELSD) were used. A simple method to quantify ELSD
      data is presented. Each data point from the ELSD chromatogram can be converted
      into a mass concentration using experimental calibration curves. The qualitative
      and quantitative information obtained on two representative samples is used to
      demonstrate the applicability of LC x SEC for determining the mutually dependent
      molar-mass distributions (MMD) and functionality-type distributions (FTD) of
      functional polymers. The influence of the molar mass on the retention behavior in
      LC was investigated using LC x SEC for hydroxyl-functional PMMA polymers. The
      critical conditions, at which retention is--by definition--independent of molar
      mass, were not exactly the same for PMMA series with different end-groups. Our
      observations are in close agreement with theoretical curves reported in the
      literature. However, for practical applications of LC x SEC it is not strictly
      necessary to work at the exact critical solvent composition. Near-critical
      conditions are often sufficient to determine the mutually dependent distributions
      (MMD and FTD) of functional polymers.

PMID- 15974070
TI  - A L-RNA aptamer chiral stationary phase for the resolution of target and related
      compounds.
AB  - In this paper, we report for the first time an aptamer-based chiral stationary
      phase (CSP) able to resolve racemates of both target and various related
      compounds. The enantiomers of tyrosine and analogues (11 enantiomeric pairs) were
      separated using an immobilized tyrosine-specific L-RNA aptamer as CSP and an
      aqueous buffer (8 mM Tris-HCl buffer, 25 mM NaCl, 5 mM MgCl2; pH 7.4) as mobile
      phase, at a column temperature of 10 degrees C. It appeared that the carboxylic
      and amino groups as well as the aromatic side chain of amino acid controlled the
      stereospecific recognition. Modifications on the polar groups were strongly
      detrimental for enantioselectivity while the replacement of the phenolic group by
      some bicyclic aromatic residues of different polarity, size or shape did not
      impair the enantioselective interaction. In addition, the effects of the mobile
      phase composition and column temperature upon the retention and stereoselective
      properties of the CSP were assessed. Finally, it was found that the immobilized
      RNA aptamer could be used under hydro-organic mobile phase conditions without
      alteration of the stationary phase stability.

PMID- 15974071
TI  - High-performance catalytic chromatography. The adapter approach.
AB  - A sequence-specific DNA that binds EcoRI endonuclease was immobilized on
      glycidioloxypropyl-silica and Sepharose by cyanogen bromide (CNBr)-activated
      coupling. Elution of bound enzyme by conventional affinity strategies (increase
      of salt concentration) or by catalysis-induced elution (adding a Mg2+ cofactor
      required for catalysis) was compared. Greater yield and fold-purification was
      obtained with catalysis-induced elution for both DNA-silica and DNA-Sepharose
      columns, and silica gives higher performance than Sepharose. Sodium
      dodecylsulfate polyacrylamide gel electrophoresis showed primarily a single band
      for EcoRI endonuclease for catalysis-induced elution from DNA-silica columns.
      Since catalysis-induced elution decreases the lifetime of DNA affinity columns,
      an alternative approach for preparing re-usable DNA columns was also developed.
      In this approach, a single stranded adapter DNA sequence is first coupled to
      silica or Sepharose and then annealed with another DNA sequence that contains a
      complementary, single stranded tail and the duplex binding site for EcoRI
      endonuclease. After use, replacing the hydrolyzed DNA regenerates the column. For
      this adapter approach, Sepharose gives better purity than silica and comparable
      yields and catalytic based elution gave the highest purity and yield, regardless
      of support. Substrate DNA with either a tail (for annealing to the column) at one
      end or both ends were compared and the former gave higher purity. Finally, enzyme
      binding to the substrate in solution ("trapping") or on a pre-bound substrate
      column was compared and trapping gave higher yield and similar purity to the
      alternative. Thus, trapping with a single tailed substrate oligonucleotide on a
      Sepharose adapter column and using catalytic elution gave the highest
      performance.

PMID- 15974072
TI  - Effects of sequence and structure in the separation of nucleic acids using ion
      pair reverse phase liquid chromatography.
AB  - Ion pair reverse phase high performance liquid chromatography on non-porous
      alkylated poly(styrene-divinylbenzene) particles enables the high resolution
      separation of double stranded DNA fragments. To further understand the separation
      mechanisms involved in ion pair reverse phase liquid chromatography we have
      analysed the effects of curved or "bent" DNA fragments with respect to their
      separation using both gel electrophoresis and ion pair reverse phase liquid
      chromatography. Size dependent separations of curved DNA fragments that migrate
      anomalously during gel electrophoresis were observed using ion pair reverse phase
      liquid chromatography. To further study the sequence effect and resulting changes
      in hydrophobicity of the duplex DNA, PCR fragments were generated that contain
      uracil in place of thymine. The resulting fragments were shown to elute with
      shorter retention times, demonstrating that sequence-specific effects can alter
      the retention of duplex DNA. The study was extended to the investigation of non
      canonical B-DNA structures (Holliday junctions) under various chromatographic
      conditions, demonstrating that the coaxial stacking of the helices in such
      structures, in the presence of magnesium causes a change in retention.

PMID- 15974073
TI  - Determination of azolic fungicides in wine by solid-phase extraction and high
      performance liquid chromatography-atmospheric pressure chemical ionization-mass
      spectrometry.
AB  - A method for simultaneous analysis of eight azolic fungicides: cyproconazole,
      diniconazole, tetraconazole, thiabendazole, flusilazole, triadimenol,
      triadimefon, carbendazim and the degradation product 2-aminobenzimidazole in wine
      samples is described. The compounds are isolated from the samples and
      concentrated by solid-phase extraction on polymeric cartridges. The determination
      is carried out by liquid chromatography with mass spectrometric detection in
      positive ionization and selected ion monitoring modes. The influence of
      parameters such as the mobile phase composition, column temperature, corona
      current and fragmentor voltage is studied and the proposed method is validated.
      Recoveries of the nine compounds added to wine samples range from 83 to 109%,
      with relative standard deviations below 10%. The quantitation limits are between
      9 and 31 microg/L. Real wine samples are analyzed by the proposed method, also.

PMID- 15974074
TI  - Liquid chromatographic-mass spectrometric assay for simultaneous pyrimethamine
      and sulfadoxine determination in human plasma samples.
AB  - We present a liquid chromatographic-mass spectrometric assay for the simultaneous
      determination of sulfadoxine and pyrimethamine in human plasma samples. Sample
      clean-up was achieved by adding acetonitrile for protein precipitation. Gradient
      elution in only 10 min resulted in high throughput capability. Tandem mass
      spectrometric detection in multiple reaction monitoring was used for
      quantification. The developed analytical approach was successfully validated and
      was applied in the pharmacokinetic evaluation of the bioavailability between two
      sulfadoxine/pyrimethamine formulations available on the Eastern African market,
      using a cross-over design.

PMID- 15974075
TI  - Identification of the microsomal oxidation metabolites of rutaecarpine, a main
      active alkaloid of the medicinal herb Evodia rutaecarpa.
AB  - Rutaecarpine is a quinazolinocarboline alkaloid of the medicinal herb Evodia
      rutaecarpa and shows a variety of pharmacological effects. Four oxidation
      metabolites of rutaecarpine were prepared from 3-methylcholanthrene-treated rat
      liver microsomes. These metabolites had an [M + H]+ ion at m/z 304. The
      structures of metabolites were identified by comparison of their liquid
      chromatograms and mass, absorbance, and 1H NMR spectra with those of synthetic
      standards. Rutaecarpine was metabolized by microsomal enzymes to form 3-, 10-, 11
      , and 12-hydroxyrutaecarpine. The formation of 10-hydroxyrutaecarpine was highly
      induced by a cytochrome P450 1A inducer, 3-methylcholanthrene.

PMID- 15974076
TI  - Solid-phase extraction of soy isoflavones.
AB  - An automated method using solid-phase extraction (SPE) for the concentration and
      clean-up of soy isoflavone extracts is proposed in this work. Using a
      standardized sample (0.1 g of a freeze dried soybean extract/25 mL of water);
      eight SPE cartridges with a wide range of sorbents (C18, divinylbenzene and
      modified divinylbenzene) from different suppliers were evaluated and compared. A
      large variation on SPE cartridges performance was observed, especially regarding
      retention and breakthrough volume of isoflavones during sample load and washing
      steps. The most effective cartridges were the divinylbenzene based cartridges,
      especially Strata X (from Phenomenex) and HLB oasis (from Waters). Using Strata X
      cartridges, several extraction parameters, such as sample loading flow (5-15 mL
      min(-1)), extracting solvent volume (2-6 mL of methanol), pH of the extracting
      solvent and the necessity of drying the sorbent before elution, were evaluated to
      provide a fast, specific, quantitative and reproducible SPE method. The optimized
      method consists of conditioning the cartridge with 10 mL of methanol and 10 mL of
      water (10 mL min(-1)), loading 25 mL of the standardized extract onto the
      cartridges (5 mL min(-1)), washing the cartridge with 10 mL of water (10 mL min(
      1)) and finally eluting with 4 mL of methanol (10 mL min(-1)). Mean isoflavones
      recovery was 99.37% and mean intra- and inter-day reproducibility was higher than
      98%. The developed sample clean-up/concentration (6.25:1) method takes less than
      10 min and can be used in the analysis of isoflavones from soy extracts.

PMID- 15974077
TI  - Screening and analysis of bioactive compounds with biofingerprinting chromatogram
      analysis of traditional Chinese medicines targeting DNA by microdialysis/HPLC.
AB  - Biofingerprinting chromatogram analysis, which is defined as the comparison of
      fingerprinting chromatograms of the extract of traditional Chinese medicines
      (TCMs) before and after the interaction with biological systems (DNA, protein,
      cell, etc.), was proposed for screening and analysis of the multiple bioactive
      compounds in TCMs. A method of microdialysis sampling combined with high
      performance liquid chromatography (HPLC) was applied to the study of DNA-binding
      property for the extracts of TCMs. Seven compounds were found to bind to calf
      thymus DNA (ct-DNA) from the TCMs of Coptis chinensis Franch (Coptis), but only
      three ones from Phellodendron amurense Rupr. (Phellodendron) and none from
      Sophoraflavescens Ait. (Sophora) to bind to ct-DNA, respectively. Three of them
      were identified as berberine, palmatine and jatrorrhizine and their association
      constants (K) to ct-DNA were determined by microdialysis/HPLC. Competitive
      binding behaviors of them to ct-DNA were also investigated.

PMID- 15974078
TI  - Isolation and purification of coumarin compounds from the root of Peucedanum
      decursivum (Miq.) Maxim by high-speed counter-current chromatography.
AB  - A preparative high-speed counter-current chromatography (HSCCC) method for
      isolation and purification of coumarin compounds from the Chinese medicinal plant
      Peucedanum decursivum (Miq.) Maxim (Zihuaqianhu in Chinese) was successfully
      established by using light petroleum-ethyl acetate-methanol-water (5:5:7:4, v/v)
      as the two-phase solvent system. The upper phase of light petroleum-ethyl acetate
      methanol-water (5:5:7:4, v/v) was used as the stationary phase of HSCCC.
      Nodakenetin (2.8 mg), 6.1 mg of Pd-C-IV, 7.3 mg of Pd-D-V, 4.7 mg of ostruthin,
      7.8 mg of decursidin and 11.2 mg of decursitin C with the purity of 88.3%, 98.0%,
      94.2%, 97.1%, 97.8% and 98.4%, respectively, were separated successfully in one
      step separation from 150 mg of crude sample from P. decursivum (Miq.) Maxim.
      After purified by HSCCC again with light petroleum-ethyl acetate-methanol-water
      (5:5:4:5, v/v) as the two-phase solvent system, the purity of (I) can reach
      99.4%. The structures of all the compounds were identified by 1H NMR and 13C NMR.

PMID- 15974079
TI  - Analysis of potential and free furfural compounds in milk-based formulae by high
      performance liquid chromatography. Evolution during storage.
AB  - A simple and reproducible HPLC-diode array detection method for the qualitative
      and quantitative analysis of potential and free furfural compounds (5
      hydroxymethyl-2-furaldehyde, HMF; 2-furaldehyde, F; 2-furyl methyl ketone, FMC;
      and 5-methyl-2-furaldehyde, MF) in milk-based formulae was developed and
      validated. The method showed good linearity with determination coefficients over
      0.999. The limits of detection and quantification were acceptable for all
      furfurals. The relative standard deviations (RSDs) for repeatability and
      reproducibility were <4.28. Recoveries in all furfurals were between 94.5 and
      98.7%. In addition, we report the evolution over shelf life of furfural compound
      levels in an experimental powder formula for pregnant women stored at 25 and 37
      degrees C from production until 15 months.

PMID- 15974080
TI  - Calibration of a detector for nonlinear chromatography.
AB  - In many studies of nonlinear or preparative chromatography, chromatographic
      signals must be recorded for relatively concentrated solutions and the detectors,
      that are designed for analytical applications and are highly sensitive, must be
      used under such experimental conditions that their responses are often nonlinear.
      Then, a calibration curve is needed to derive the actual concentration profiles
      of the eluates from the measured detector response. It becomes necessary to
      derive a relationship between the concentration of the eluent and the detector
      signal at any given time. The simplest approach consists in preparing a series of
      solutions of known concentrations and in flushing them successively through the
      detector cell, recording the height of the plateau response obtained. However,
      this method requires relatively large amounts of the pure solutes being studied
      and these are not always available or they may be most costly, although these
      solutions can be recovered. We describe and validate an alternative procedure
      providing this calibration from a series of peaks recorded upon the injection of
      increasingly large pulses of the studied compound.

PMID- 15974081
TI  - 2,3-di-O-methoxymethyl-6-O-tert-butyldimethylsilyl-beta-cyclodextrin, a useful
      stationary phase for gas chromatographic separation of enantiomers.
AB  - Heptakis(2,3-di-O-methoxymethyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin
      (2,3-MOM-6-TBDMS-beta-CD), synthesized by using methoxymethylchloride (MOM-Cl) as
      derivatization reagent, was used for capillary gas chromatographic separation of
      enantiomers. The new chiral stationary phase proved to be suitable for the
      enantiodifferentiation of volatiles from various chemical classes. Compared to
      the corresponding gamma-CD derivative (2,3-MOM-6-TBDMS-gamma-CD), the spectrum of
      compounds for which enantiomers could be separated was more limited and the
      enantioseparation achieved was generally less pronounced. Unusually high
      separation factors were observed for 2-alkyl esters of short chain acids (C2-C6).
      Phenomena underlying the enantioseparation of 2-pentyl acetate (alpha: 4.31; 35
      degrees C) were investigated by determining thermodynamic parameters. Data show
      that only one enantiomer is retained significantly on the chiral stationary phase
      whereas the other one behaves like the hydrocarbons used as references.

PMID- 15974082
TI  - High-performance liquid chromatographic separation and chiroptical properties of
      the enantiomers of naringenin and other flavanones.
AB  - The HPLC enantiomeric separation of naringenin, eriodictyol, hesperetin and
      pinocembrin was accomplished in the normal-phase mode using two polysaccharide
      derived chiral stationary phases (Chiralcel OD-H and Chiralpak AS-H) and various
      n-hexane/alcohol mobile phases. The 3',4' substituents pattern affect the
      enantioselectivity of these phases. Single enantiomers of naringenin were
      isolated by semipreparative HPLC and their CD spectra were measured and related
      to the absolute configuration by the exciton-coupling method. Online coupling
      HPLC/spectropolarimeter afforded the CD sign of the eluted peaks at a single
      wavelength, and the complete CD spectra of the eluted enantiomers were obtained
      by trapping them in the spectropolarimeter cell through a switching valve.

PMID- 15974083
TI  - Application of artificial neural networks for prediction of retention factors of
      triazine herbicides in reversed-phase liquid chromatography.
AB  - In this paper a quantitative structure-retention relationship (QSRR) method is
      used to model reversed-phase high-performance liquid chromatography (HPLC)
      behaviour of a series of triazine herbicides and their metabolites. Accurate
      description of the retention factors in terms of four descriptors related to the
      analytes and to the mobile phase is achieved by means of an artificial neural
      network (ANN). For comparison, a QSRR model is derived by multilinear regression
      (MLR). Validation of the two models shows a better ability in prediction of the
      ANN as compared with the MLR method. A solid-phase extraction (SPE) procedure
      allowing the simultaneous determination of the five triazinic compounds in
      groundwater analysis is also presented. The observed recoveries from water
      samples range between 85 and 100% for ng/ml concentration levels of all analytes.

PMID- 15974084
TI  - Analysis of the essential oil from aerial parts of Eupatorium cannabinum subsp.
      corsicum (L.) by gas chromatography with electron impact and chemical ionization
      mass spectrometry.
AB  - Eupatorium cannabinum subsp. corsicum (L.), an aromatic plant, is an endemic
      subspecies from Corsica. The essential oil from aerial parts of E. cannabinum
      subsp. corsicum was studied by GC, GC/MS and 13C NMR. One hundred and forty-seven
      components were identified representing 93.6% of the total amount. The main
      constituents are germacrene D (28.5%), alpha-phellandrene (19.0%) and para-cymene
      (5.2%). A particularity of this essential oil is the presence of monoterpene
      esters derived from nerol, lavandulol, borneol, thymol and 8,9-dehydrothymol.
      These compounds have been investigated using GC/MS in different ionization modes
      like electron impact (EI), positive chemical ionization (PCI) and negative
      chemical ionization (NCI).

PMID- 15974085
TI  - Development of a headspace gas chromatography method to determine residual
      aliphatic amines in oligonucleotides.
AB  - A headspace gas chromatographic method has been developed for analysis of
      aliphatic amines in oligonucleotides. The linearity was improved by including
      ammonia in the sample vials. Also, carryover of longer chain primary amines,
      hexylamine and octylamine, was substantially reduced by cleaning the injection
      syringe with ammonia and water vapor between sample injections.

PMID- 15974086
TI  - Enantioseparation of 1-phenyl-1-propanol on Chiralcel OD by supercritical fluid
      chromatography. I. Linear isotherm.
AB  - The supercritical fluid chromatography (SFC) separation of the enantiomers of 1
      phenyl-1-propanol on the chiral stationary phase Chiralcel OD under linear
      conditions is studied. Supercritical CO2 modified with methanol is used as a
      mobile phase. The effect of modifier concentration, pressure and temperature is
      studied. An empirical isotherm to account for the effect of density of the mobile
      phase and modifier concentration has been used to model the experimental results.
      It was observed that the selectivity and resolution were higher at 30 degrees C
      as compared to those at 40 degrees C.

PMID- 15974087
TI  - Preparative isolation and characterization of some minor impurities of
      astaxanthin by high-performance liquid chromatography.
AB  - A simple and rapid preparative high-performance liquid chromatography (HPLC)
      method has been developed to isolate and characterize some minor impurities of
      astaxanthin using a normal-phase Lichrosorb silica column with n-hexane-acetone
      tetrahydrofuran (90:2:8, v/v/v) as mobile-phase and detection at 475 nm. The
      isolated impurities were characterized as astacene, dehydro astacene and
      apoastaxanthinal by UV-vis, ESI-MS, 1H and 13C NMR spectroscopy and the molecular
      structures were assigned. The impurities collected using the developed conditions
      were over 98% pure.

PMID- 15974088
TI  - Preparative isolation and purification of costunolide and dehydrocostuslactone
      from Aucklandia lappa Decne by high-speed counter-current chromatography.
AB  - A preparative high-speed counter-current chromatography (HSCCC) method for
      isolation and purification of costunolide and dehydrocostuslactone from the
      Chinese medicinal plant Aucklandia lappa Decne (Muxiang in Chinese) was
      successfully established by using light petroleum-methanol-water (5:6.5:3.5,
      v/v/v) as the two-phase solvent system. The upper phase of light petroleum
      methanol-water (5:6.5:3.5, v/v/v) was used as the stationary phase of HSCCC. 35.7
      mg of costunolide and 43.6 mg of dehydrocostuslactone with the purity of 100% and
      99.6%, respectively, were separated successfully in one-step separation from 110
      mg of crude sample from Aucklandia lappa Decne. The structures of costunolide and
      dehydrocostuslactone were identified by 1H NMR and 13C NMR.

PMID- 15974089
TI  - Preparative isolation and purification of rupestonic acid from the Chinese
      medicinal plant Artemisia rupestris L. by high-speed counter-current
      chromatography.
AB  - Rupestonic acid was purified for the first time by high-speed counter-current
      chromatography from a dichloromethane extract of the traditional Chinese
      medicinal plant Artemisia rupestris L. The separation was performed in two steps
      with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water
      (6:4:3.5:6.5, v/v) with 0.5% acetic acid in stationary-phase. From 200 mg of the
      crude extract, 27.9 mg of rupestonic acid was obtained at over 98% purity as
      determined by HPLC analysis, and its chemical structure was confirmed by MS, 1H
      and 13C nuclear magnetic resonance.

PMID- 15974090
TI  - Capillary liquid chromatography of chlorophenoxy acid herbicides and their esters
      in apple juice samples after preconcentration on a cation exchanger based on
      polydivinylbenzene-N-vinylpyrrolidone.
AB  - A capillary liquid chromatography (cLC) method with gradient elution has been
      used to determine chlorophenoxy acid herbicides: 2,4-dichlorophenoxyacetic acid,
      4-chloro-2-methylphenoxyacetic acid, 2-(2,4-dichlorophenoxy)propanoic acid, 2-(4
      chloro-2-methylphenoxy)propanoic acid, 4-(2,4-dichlorophenoxy)butanoic acid, 4-(4
      chloro-2-methylphenoxy)butanoic acid, 2-(2,4,5-trichlorophenoxy)propanoic acid,
      2,4-dichlorophenoxyacetic-1-methyl ester and 2,4-dichlorophenoxyacetic-1-butyl
      ester in spiked apple juice samples with amounts between 0.025 and 0.150 mg kg(
      1) of each herbicide. Clean-up and preconcentration of acid and esters were
      carried out in an Oasis MCX polymer. Detection limits obtained by cLC, between
      0.005 and 0.018 mg kg(-1), allowed the determination of chlorophenoxy acids and
      their esters in apple juice samples around the levels permitted by the European
      Regulations, with recoveries in the range 84-99% and RSDs between 1 and 4%.

PMID- 15974091
TI  - Preparative counter-current chromatography purification of valrubicin (AD-32)
      from crude synthetic drug using upright coil planet centrifuge with four
      multilayer coils connected in series.
AB  - Preparative counter-current chromatography (CCC) purification of valrubicin (AD
      32) from crude synthetic drug has been successfully performed for the first time
      using upright coil planet centrifuge with four multilayer coils connected in
      series with 1600 ml capacity. The two-phase system used was composed of light
      petroleum (bp 60-90 degrees C)-ethyl acetate-tetrachloromethane-methanol-water at
      an optimized volume ratio of 1:1:8:6:1. Target compound (1.2 g) with a purity of
      99.88% was obtained from 1.5 g of crude synthetic drug with a purity 95.49% based
      on HPLC peak area percentage. Identification of the target compound was performed
      by electrospray ionization mass spectrometry, one- and two-dimensional nuclear
      magnetic resonance.

PMID- 15974092
TI  - Application of preparative high-speed counter-current chromatography for
      separation of methyl gallate from Acer truncatum Bunge.
AB  - Preparative separation of methyl gallate in leaves extract of Acer truncatum
      Bunge was conducted using high-speed counter-current chromatography (HSCCC) with
      a solvent system composed of ethyl acetate-ethanol-water at volume ratios of
      5:1:5 (v/v/v). In a single operation, 57.5 mg of methyl gallate was obtained from
      120 mg of the extract. HPLC analyses of the counter-current chromatography (CCC)
      fraction revealed that the methyl gallate was having over 97% purity. Its
      structure was identified by 1H NMR and 13C NMR.

PMID- 15974093
TI  - Evaluation of the effects of various gas chromatographic parameters on haloacetic
      acids disinfection by-products analysis.
AB  - Thermal decomposition of the analytes during the analysis is a problem for
      haloacetic acids (HAAs). We evaluated the effect of GC injection port temperature
      and the amount of trace water in the sample on the HAAs' analysis. For three
      brominated HAAs, the variation in intensity due to the change of injection port
      temperature was significant. The largest variation observed was tribromoacetic
      acid methyl ester (from 3.2 to 1 for injection port temperature changing from 170
      degrees C to 250 degrees C). Tribromoacetic acid methyl ester partially
      decomposed to dibromoacetic acid and to tribromomethane in a competitive way. At
      a low injection port temperature, tribromomethane formation was preferred, but at
      a high injection port temperature, the debrominated methyl ester formation
      dominated. Water contained in the sample may accelerate the hydrolysis process of
      the esters in the injection port, and this effect was also the greatest for the
      brominated trihaloacetic acids. Direct injection of underivatized HAAs into the
      GC/MS indicated that brominated HAAs can be nearly quantitatively thermal
      decomposed to the corresponding halomethanes.

PMID- 15974094
TI  - Comments on the "classical equations" given in J. Chromatogr A 1024 (2004) 195
      207.

PMID- 15974095
TI  - TennCare in crisis.

PMID- 15974096
TI  - "The sun also rises" in Tennessee.

PMID- 15974097
TI  - Who can give injections and IVs?

PMID- 15974098
TI  - Long journey ahead on medical malpractice reform.

PMID- 15974099
TI  - Medicare cuts: Jeopardizing a generation.

PMID- 15974100
TI  - The way it is now.

PMID- 15974101
TI  - Here to help: annual PHP activity report.

PMID- 15974102
TI  - The case for ePrescribing.

PMID- 15974103
TI  - Gatifloxacin-induced cholestatic hepatitis--a challenging diagnosis.

PMID- 15974104
TI  - Tennessee trauma care system plan, Part 1.
AB  - Tennessee implemented a statewide trauma care system in 1988. This system serves
      the state of Tennessee and supports eight neighboring states. The demographics
      and geography of Tennessee have ensured that nearly all residents have rapid
      access to the trauma care system. However, since 1988, many changes have occurred
      in healthcare in general, and trauma care in particular, that point out problems
      and issues with the Tennessee trauma care system. Therefore, the Tennessee Trauma
      Care Advisory Council has developed this Trauma Care System Plan to look at needs
      and opportunities for the future of trauma care in Tennessee. This plan will be
      presented in four segments: History, Administrative Components, Operational
      Components, and Clinical Components.

PMID- 15974105
TI  - The placebo: promise and compromise.

PMID- 15974106
TI  - Avoid overload: assign cases based on workload, model, and role functions.

PMID- 15974107
TI  - Internet resources help you study for CCM exam. Guide gives overview of exam,
      sample questions.

PMID- 15974108
TI  - Proactive case management initiatives help cut LOS.

PMID- 15974109
TI  - Patient safety alert. Small hospital makes big strides in safety.

PMID- 15974110
TI  - Work as a team to meet needs of all your patients.

PMID- 15974112
TI  - Solutions often found in existing technology.

PMID- 15974111
TI  - Project examines why patients don't take meds.

PMID- 15974113
TI  - Occurrence and analytical methods of acrylamide in heat-treated foods. Review and
      recent developments.
AB  - In early 2002, Swedish National Food Administration (SNFA) and University of
      Stockholm together announced that certain foods that are processed or cooked at
      high temperature contain relatively high levels of acrylamide. The occurrence of
      acrylamide is derived from heat-induced reactions between the amino group of
      asparagine and the carbonyl group of reducing sugars during baking and frying.
      Corresponding chromatographic methods are used to determine various structural
      groups present during this process. Gas chromatography (GC)-mass spectrometry
      (MS) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis
      are both acknowledged as the major useful and authoritative methods for the
      acrylamide determination and other chromatographic methods are also briefly
      introduced. The aim of this review is to summarize the state-of-the-art about the
      occurrence, analytical methods, and extraction and clean-up procedures of
      acrylamide. Special attention is given to chromatographic techniques applied for
      the occurrence and determination of acrylamide.

PMID- 15974114
TI  - Complexities in tetracycline analysis-chemistry, matrix extraction, cleanup, and
      liquid chromatography.
AB  - The extraction and cleanup of commonly used tetracyclines (oxytetracycline,
      tetracycline, chlortetracycline, and doxycycline) from sample matrix, and their
      subsequent determination via liquid chromatography can be problematic. Many
      manuscripts report on various challenges encountered when developing a method for
      tetracycline antibiotics determination. These complexities often result in less
      than perfect recoveries or chromatograms and are based on the underlying
      chemistry associated with tetracyclines. This review compiles, compares, and
      discusses the results and observations found in published methods, while focusing
      on chemical principles in order to increase the practicing chemist's
      understanding of TCs to aid him/her in developing useful analyses.

PMID- 15974115
TI  - Two-step recovery process for tryptophan tagged cutinase: interfacing aqueous two
      phase extraction and hydrophobic interaction chromatography.
AB  - In this work, the interfacing of a poly(ethylene glycol) (PEG)-phosphate aqueous
      two-phase system with hydrophobic interaction chromatography (HIC) for primary
      recovery of an intracellular protein was evaluated. As a model protein, a
      recombinant cutinase furnished with a tryptophan-proline (WP) peptide tag was
      used and produced intracellularly in Escherichia coli (E. coli). E. coli cell
      homogenate was partitioned in a two-phase system and the top phase yield,
      concentration and purity of the tagged ZZ-cutinase-(WP)4 was evaluated as
      function of polymer sizes, system pH and phase volume ratio. The partition
      behaviour of cell debris, total protein and endotoxin was also monitored. In the
      HIC part, the chromatographic yield and purity was investigated with respect to
      ligand hydrophobicity, dilution of loaded top phase and elution conditions. Based
      on the results, a recovery process was demonstrated where a PEG 1500-K-Na
      phosphate salt aqueous two-phase system was interfaced with a HIC column. The
      interfacing was facilitated by the Trp-tagged peptide. The tagged ZZ-cutinase
      (WP)4 was obtained in a PEG-free phase and purified to >95% purity according to
      silver stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) gels with a total yield of 83% during the two-step recovery process.

PMID- 15974116
TI  - Stir bar sorptive extraction based on restricted access material for the direct
      extraction of caffeine and metabolites in biological fluids.
AB  - A biocompatible stir bar sorptive extraction (SBSE) device was prepared using an
      alkyl-diol-silica (ADS) restricted access material (RAM) as the SBSE coating. The
      RAM-SBSE bar was able to simultaneously fractionate the protein component from a
      biological sample, while directly extracting caffeine and its metabolites,
      overcoming the present disadvantages of direct sampling in biological matrices by
      SBSE, such as fouling of the extraction coating by proteins. Desorption of the
      analytes was performed by stirring the bar in a water/ACN mixture (3/1, v/v) and
      subsequently reconcentrating the sample solution in water to enable HPLC-UV
      analysis to be performed. The limit of detection, based on a signal to noise
      ratio of 3, for caffeine was 25 ng/mL in plasma. The method was confirmed to be
      linear over the range of 0.5-100 microg/mL of caffeine with an average linear
      coefficient (R2) value of 0.9981. The injection repeatability and intra-assay
      precision of the method were evaluated over ten injections, resulting in a %RSD
      of approximately 8%. The RAM-SBSE device was robust (>50 extraction in plasma
      without significant signal loss) and simple to use, providing many direct
      extractions and subsequent determination of caffeine and its metabolites in
      biological fluids. In contrast to existing sample preparation methods for the
      analysis of caffeine and selected metabolites in biological fluids, this
      feasibility study using a biocompatible SBSE approach was advantageous in terms
      of simplifying the sample preparation procedures.

PMID- 15974117
TI  - Evaluation of a new hypercrosslinked polymer as a sorbent for solid-phase
      extraction of polar compounds.
AB  - A new hypercrosslinked polymer (HXLGp) with hydrophilic character due to the
      presence of hydroxyl moieties has been tested as a sorbent for the solid-phase
      extraction (SPE) of several polar compounds from water samples. This new sorbent
      enables the on-line extraction of 300 ml of sample with recoveries higher than
      80% for polar compounds such as oxamyl, methomyl or desisopropylatrazine (DIA).
      The HXLGp has also been compared to other commercially available sorbents such as
      Oasis HLB (hydrophilic macroporous), to hydrophobic hypercrosslinked resins and
      to a previously synthesized sorbent based on N-vinylimidazole-divinylbenzene. The
      results are consistently better with the new synthesized sorbent. The method was
      successfully applied to the on-line SPE-HPLC of tap and river water samples. The
      validation with river water samples provided good linearity range and detection
      limits between 0.03 for methomyl and 4-nitrophenol (4NP) to 0.2 microg l(-1) for
      phenol (Ph).

PMID- 15974118
TI  - Study of overloading of basic drugs and peptides in reversed-phase high
      performance liquid chromatography using pH adjustment of weak acid mobile phases
      suitable for mass spectrometry.
AB  - Serious losses in column efficiency for ionised basic drugs and peptides occur
      due to overloading of C18 phases when weak acid mobile phases of low ionic
      strength suitable for mass spectrometric detection are used. Measurable changes
      in retention time and efficiency can be observed even for levels around 0.01
      microg of basic drugs on 0.46 cm I.D. columns; the overloading process is a
      continuum, rather than an event which takes place only once a certain threshold
      value has been reached. Overloading can be reduced by increasing the mobile phase
      pH, e.g to the pKa of the weak acid, which increases the ionic strength, allowing
      a greater degree of ion pairing and perhaps also physical screening of the
      adsorbed solute ions by buffer ions. Buffer capacity is also optimum at its pKa.
      Silanol ionisation and kinetic tailing effects were mostly absent at aqueous pH
      up to 4.75 on the hybrid inorganic-organic C18 phase employed in this study,
      except when analysing the most highly charged peptides. The exact cause of
      overloading of these ionic species is unclear.

PMID- 15974120
TI  - Separation of amino acids with simulated moving bed chromatography*.
AB  - Authors have constructed an automatized four-column large laboratory scale (I.D.
      = 50 mm, L = 500 mm) simulated moving bed (SMB) equipment. The applied model
      system for separation of biomolecules is glycine, L-phenylalanine, water and
      Sepabeads SP825 adsorbent. The authors determined the adsorption equilibrium data
      and the packing characteristics. The operating conditions of SMB equipment were
      calculated with the help of the Morbidelli variables. During the SMB experiments,
      glycine and L-phenylalanine were separated in water on Sepabeads SP825 with an
      average particle size 0.3 mm at temperatures 20 degrees C and 60 degrees C. The
      measurement series were carried out on a four-column three-zone open loop SMB.
      Both L-phenylalanine and glycine were produced with more than 99.9% (m/m) purity
      and 99% yield at productivity 1.7-3.7, with productivity 3.7-8.1 mg/(g adsorbent
      h) in case of 2-1-1-0 column configuration. The measured and the calculated data
      agreed well.

PMID- 15974119
TI  - Solvent versatility of immobilized 3,5-dimethylphenylcarbamate of amylose in
      enantiomeric separations by HPLC.
AB  - CHIRALPAK IA is a new chiral stationary phase containing amylose 3.5
      dimethylphenylcarbamate immobilized onto silica gel. It is compatible with the
      whole range of organic solvents. Its solvent versatility has been thoroughly
      investigated. The option to use a wide range of solvents, especially the "non
      standards" ones, in the mobile phase enables the enhancement of chiral separation
      methods in terms of enantioselectivity, resolution, analysis time, sample
      injection and sample solubility. Parameters such as the mobile phase type, the
      nature of modifier and eluting strength of various solvents are examined and
      discussed. A guideline for method development and optimization on CHIRALPAK IA is
      also proposed.

PMID- 15974121
TI  - High-performance liquid chromatographic stationary phases based on
      poly(dimethylsiloxane) immobilized on silica.
AB  - This work describes the preparation and characterization of six stationary phases
      for high-performance liquid chromatography (HPLC) obtained by deposition of
      poly(dimethylsiloxane) (PDMS) in HPLC silica particles, followed by
      immobilization using different processes (thermal treatments, thermal treatment +
      microwave irradiation, self-immobilization + gamma irradiation and self
      immobilization + microwave irradiation). The chromatographic parameters of all
      the phases were evaluated with a mixture of test compounds having varied natures
      (acid, basic and neutral). The stability of one of these phases was evaluated in
      both a neutral mobile phase and a higher pH mobile phase used at an elevated
      temperature, with promising results.

PMID- 15974122
TI  - Characterisation of glycoprotein ligands synthesised using solid-phase
      combinatorial chemistry.
AB  - A combination of rational design based on mimicking natural protein-carbohydrate
      interactions and solid-phase combinatorial chemistry has led to the
      identification of an affinity ligand which displays selectivity for the mannose
      moiety of glycoproteins. The ligand was initially identified as 32/18, a triazine
      scaffold substituted with 2-acetylpyrrole (32) and 5-aminoindan (18). However,
      characterisation of the immobilised ligand by release from the matrix via a
      cleavable linker, (4s,5s)-4,5-di(aminomethyl)-2,2-dimethyldioxolane, and using a
      non-destructive on-resin method, 13C NMR spectroscopy, confirmed that the
      putative ligand 32/18 was, in fact, 18/18, the disubstituted 5-aminoindan. 1H NMR
      studies on the interaction of alpha-D-methylmannoside with the ligand 18/18 in
      solution confirm the involvement of the hydroxyl group in the C-2 position.

PMID- 15974124
TI  - Comparative characteristics of HPLC columns based on quantitative structure
      retention relationships (QSRR) and hydrophobic-subtraction model.
AB  - The study was aimed at quantitative comparison of retention properties of modern
      stationary phases for reversed-phase HPLC. Three approaches, the calculated
      logarithm of octanol/water partition coefficient (clogP)-based model, the
      molecular modeling descriptors-based model and the hydrophobic-subtraction model,
      were compared and discussed. Gradient retention time, tR, of a series of test
      analytes was a dependent variable in the quantitative structure-retention
      relationship (QSRR) equations describing retention in terms of analytes'
      structure descriptors. The QSRRs derived were used to characterize in
      quantitative manner the specific retention properties of nine representative
      reversed-phase HPLC. Either the theoretically calculated logarithm of
      octanol/water partition coefficient, or the structural descriptors from molecular
      modeling were employed to quantitatively characterize the structure of the
      analytes. The three molecular modeling-derived structural descriptors considered
      were: the total dipole moment, the electron excess charge of the most negatively
      charged atom and the water-accessible molecular surface area. In addition to the
      above standard QSRR approaches, a recently developed parameterization of reversed
      phase column selectivity based on the hydrophobic-subtraction model of Snyder et
      al. [L.R. Snyder, J.W. Dolan, J.W. Carr, The hydrophobic-subtraction model of
      reversed-phase column selectivity, J. Chromatogr. A 1060 (2004) 77] was
      considered. According to the hydrophobic-subtraction model, reversed-phase
      columns are characterized by five selectivity parameters derived from the linear
      solvation energy relationships (LSER) theory. Values of these parameters are
      available for more than 300 different columns. It has been demonstrated that the
      clogP-based model, the molecular modeling descriptors-based model and the
      hydrophobic-subtraction model provide generally similar classification of the
      HPLC columns studied. Some differences in column classification by the three
      approaches considered are discussed in terms of specific properties of individual
      stationary phases. All the approaches allow a quantitative, although
      multidimensional, characteristic of HPLC columns, however, the nonempirical QSRR
      based approach is simpler and require less labor.

PMID- 15974123
TI  - One-step purification and characterization of an alkaline protease from
      haloalkaliphilic Bacillus sp.
AB  - An alkaline protease producer haloalkaliphilic bacteria (isolate Vel) was
      isolated from west coast of India. It was related to Bacillus pseudofirmus on the
      basis of 16S r RNA gene sequencing, lipid profile and other biochemical
      properties. The protease secreted by this bacteria was purified 10-fold with 82%
      yield by a single step method on Phenyl Sepharose 6 Fast Flow column. The
      apparent molecular mass based on the sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was estimated to be 29 000 Da. The Km and Vmax towards
      caseinolytic activity were found to be 2 mg ml(-1) and 289.8 microg min(-1),
      respectively. The enzyme was active over the pH range of 8.5-12.0, the optimum
      being 10-11.0. The purified enzyme when kept at 45 degrees C and 50 degrees C for
      40 min retained 92% and 85% protease activity, respectively. Effect of NaCl
      concentration on protease activity showed that the enzyme was slightly inhibited
      with high concentration of salt. The proteolytic activity was inhibited by PMSF,
      suggesting that the enzyme may belong to serine type protease. Interestingly, the
      activity was slightly enhanced with SDS (0.1%) and Triton X-100 (0.1%) but
      remained unaffected by Tween 80 (0.1%). The activity was affected by metal ions
      to varying extent. While Mn2+, Zn2+ and Mg2+ had no significant effect on
      protease activity, the enzyme was activated with Ca2+ (1 mM) and Cu2+ (5 mM). The
      stability of the enzyme in the presence of detergent components and surfactants
      is particularly attractive for its application in detergent industries.

PMID- 15974125
TI  - Influence of the pressure on the properties of chromatographic columns .III.
      retention volume of thiourea, hold-up volume, and compressibility of the C18
      bonded layer.
AB  - The influence of the average column pressure (ACP) on the elution volume of
      thiourea was measured on two RPLC columns, packed with Resolve-C18 (surface
      coverage 2.45 micromol/m2) and Symmetry-C18 (surface coverage 3.18 micromol/m2),
      and it was compared to that measured under the same conditions on an
      underivatized silica (Resolve). Five different methanol-water mixtures (20, 40,
      60, 80 and 100% methanol, v/v) were used. Once corrected for the compressibility
      of the mobile phase, the data show that the elution volume of thiourea increases
      between 3 and 7% on the C18-bonded columns when the ACP increases from 50 to 350
      bar, depending on the methanol content of the eluent. No such increase is
      observed on the underivatized Resolve silica column. This increase is too large
      to be ascribed to the compressibility of the stationary phase (silica + C18
      bonded chains) which accounts for less than 5% of the variation of the retention
      factor. It is shown that the reason for this effect is of thermodynamic origin,
      the difference between the partial molar volume of the solute in the stationary
      and the mobile phase, Delta V, controlling the retention volume of thiourea.
      While Delta V is nearly constant for all mobile phase compositions on Resolve
      silica (with Delta V approximately equal to -4 mL/mol), on RPLC phases, it
      significantly increases with increasing methanol content, particularly above 60%
      methanol. It varies between -5 mL/mol and -17 mL/mol on Resolve-C18 and between 
      9 mL/mol and -25 mL/mol on Symmetry-C18. The difference in surface coverage
      between these two RP-HPLC stationary phases increases the values of Delta V by
      about 5 mL/mol.

PMID- 15974126
TI  - Isolation and purification of four flavonoid constituents from the flowers of
      Paeonia suffruticosa by high-speed counter-current chromatography.
AB  - Four flavonoids, apigenin-7-O-neohesperidoside, luteolin-7-O-glucoside, apigenin
      7-O-glucoside and kaempferol-7-O-glucoside have been isolated and purified for
      the first time from the flowers of Paeonia suffruticosa by high-speed counter
      current chromatography with a two-phase solvent system composed of ethyl acetate
      ethanol-acetic acid-water (4:1:0.25:5, v/v). Then, 5 mg apigenin-7-O
      neohesperidoside, 4 mg luteolin-7-O-glucoside, 9 mg apigenin-7-O-glucoside and
      2.5 mg kaempferol-7-O-glucoside could be obtained after injecting 40 mg sample
      and their purities were 94, 97, 97 and 96%, respectively. All these constituents
      were identified by mass spectrometry and nuclear magnetic resonance.

PMID- 15974127
TI  - Rapid molecular weight analysis of polymers by temperature gradient interaction
      chromatography.
AB  - Temperature gradient interaction chromatography (TGIC) has been established as a
      high-resolution technique for the characterization of synthetic polymers. So far,
      most of the TGIC investigations focused on the high-resolution analysis and
      little effort has been made on the reduction of the analysis time. In this study,
      we examined the effect of the column heating rate, the eluent flow rate, and the
      column length on the TGIC analysis time. We found that the heating rate is the
      most important experimental parameter to control the TGIC retention time. With a
      C18 silica column (50 mm x 4.6mm I.D.), a set of PS standards of wide molecular
      weight range (5 - 648 kg/mol) could be separated within 4 min at a heating rate
      of 8 degrees C/min.

PMID- 15974128
TI  - Analysis of T-2 and HT-2 toxins in cereal grains by immunoaffinity clean-up and
      liquid chromatography with fluorescence detection.
AB  - A sensitive, precise and accurate method has been developed for the simultaneous
      determination of T-2 and HT-2 toxins in cereal grains at ppb levels using high
      performance liquid chromatography (HPLC) with fluorescence detection and 1
      antroylnitrile (1-AN) as labeling reagent after immunoaffinity clean-up. Cereal
      samples were extracted with methanol/water (90:10, v/v), and the extracts were
      cleaned-up through commercially available immunoaffinity columns containing
      monoclonal anti-T-2 antibodies (T-2 test HPLC, Vicam). T-2 and HT-2 toxins were
      quantified by reversed-phase HPLC with fluorometric detection (excitation
      wavelength 381 nm, emission wavelength 470 nm) after derivatization with 1-AN.
      The monoclonal antibody showed 100% cross-reactivity with both T-2 and HT-2
      toxin, and the immunoaffinity column clean-up was effective up to 1.4 microg of
      both toxins. The method was successfully applied to the analysis of T-2 and HT-2
      toxins in wheat, maize and barley. Recoveries from spiked samples with toxin
      levels from 25 to 500 microg/kg ranged from 70% to 100%, with relative standard
      deviation generally lower than 8%. The limit of detection of the method was 5
      microg/kg for T-2 toxin and 3 microg/kg for HT-2 toxin, based on a signal-to
      noise ratio 3:1. HT-2 toxin was detected in ten naturally contaminated wheat
      samples out of 14 samples analyzed, with toxin levels ranging from 10 to 71
      microg/kg; three of them contained also T-2 toxin up to 12 microg/kg.

PMID- 15974129
TI  - Purification and determination of plant hormones auxin and abscisic acid using
      solid phase extraction and two-dimensional high performance liquid
      chromatography.
AB  - A method for separation and purification of plant hormones auxin and abscisic
      acid based on mixed mode reversed-phase anion-exchange solid phase extraction and
      two-dimensional HPLC was developed. Two-dimensional HPLC in "heart cutting" mode
      was very efficient in the purification of these two hormones. Its purification
      power is high enough to allow reliable on-line quantification of both hormones
      even with non-selective detectors.

PMID- 15974130
TI  - Fast ion chromatography of inorganic anions and cations on a lysine bonded porous
      silica monolith.
AB  - A 0.46 cm x 10.0 cm silica monolith column was modified through the in situ
      covalent attachment of lysine (2,6-diaminohexanoic acid) groups. Due to the
      zwitterionic nature of the resultant stationary phase, the modified monolithic
      column contained both cation and anion exchange capacity. In the case of cation
      exchange, the capacity was found to be relatively low at between 5 and 6.5
      micromoles Me2+ per column. However, as expected, the lysine monolith exhibited a
      higher anion exchange capacity at 12-13 micromoles A- per column (at pH 3.0),
      which was found to be dependent upon column pH, due to the dissociation of the
      weak acid carboxylic acid groups. High-performance separations of transition
      metal cations and inorganic anions were achieved using the modified monolith,
      with the effects of eluent concentration, pH and flow rate evaluated. Using
      elevated flow rates of up to 5 mL/min the separation of nitrite, bromate,
      bromide, nitrate, iodide and thiocyanate was possible in approximately 100 s with
      peak efficiencies of between 50 and 100,000 N/m and retention time %RSD of under
      0.3%.

PMID- 15974131
TI  - Mechanism of retention loss when C8 and C18 HPLC columns are used with highly
      aqueous mobile phases.
AB  - We describe investigations into the cause of retention losses encountered when C8
      and C18 HPLC columns are used with highly aqueous (> 90% water) mobile phases. A
      procedure for quantifying these losses is described, involving stopping and
      restarting the flow. This procedure was used to study the dependence of retention
      loss on the pore size, surface concentration, and chemical structure of the
      bonded phase. Experiments were also carried out to determine how to restore the
      original retention of the columns by changing the composition of the mobile
      phase, or by increasing the pressure applied to the column. The results are shown
      to be consistent with a mechanism based on the theory of pore filling by non
      wetting liquids, as employed in Mercury Porosimetry. The retention losses are
      attributed to the highly aqueous mobile phase being forced out of the pores when
      the flow is stopped and the pressure released. Retention is lost because the
      mobile phase is no longer in contact with the interior surface of the particles,
      where most of the surface area is located. The implications of this phenomenon
      for maximizing the reversed phase retention of polar analytes are discussed.

PMID- 15974132
TI  - Studies of complex reactions using modem hyphenated methods: alpha-pinene
      ozonolysis as a model reaction.
AB  - Modern analytical equipment, in this case the combinations of gas chromatography
      (GC) with mass spectrometry (MS) and infrared spectroscopy (IR) and liquid
      chromatography (LC) with mass spectrometry, nuclear magnetic resonance (NMR)
      spectroscopy and infrared spectroscopy, respectively, have been used to monitor
      complex reactions that do not only form one or two but a larger number of
      products. Additionally, side reactions of one primary product with a reactant
      form a second line of secondary products. To be able to propose formation
      pathways or even mechanistic interpretation of reactions like these,
      sophisticated analytical instrumentation is necessary to be able to observe all
      steps of such a reaction. In this case, the gas phase reaction of alpha-pinene
      with ozone has been used as a model reaction. A number of both volatile and low
      volatile reaction products could be characterized and formation pathways for a
      reaction with ozone and OH radicals were proposed.

PMID- 15974133
TI  - Ultra-short open capillary columns in gas-liquid chromatography.
AB  - New area in capillary gas chromatography (GC) was investigated. Many important
      analytical tasks can be solved only use very short capillary columns. Variation
      of chromatographic characteristics of ultra-short capillary columns with column
      length was originally studied at the conditions of gas-liquid chromatography. The
      column length varied from 500 to 10 cm. Dependencies of height equivalent to one
      theoretical plate (HETP) and separation number (SN) on carrier gas velocity were
      considered for columns of various length. Field of ultra-short open capillary
      columns in gas-liquid chromatography has the following peculiarities: (1) more
      shorter retention times of sorbates, (2) more low temperatures of short column,
      that has as final result (a) high selectivities of used column and (b) the
      possibilities to separation more thermal lability compounds. It was shown that
      short capillary columns can be successfully used at both isothermal and
      temperature programming conditions for express-analysis at lower oven
      temperatures. Examples of express-analysis (high speed), analysis of high boiling
      and thermolabile compounds are listed, which demonstrate some radically new
      applications of capillary gas chromatography.

PMID- 15974134
TI  - Development and validation of a microsomal online cytochrome P450 bioreactor
      coupled to solid-phase extraction and reversed-phase liquid chromatography.
AB  - The development and validation of an online cytochrome P450 (CYP)-based
      bioreactor coupled to automated solid-phase extraction (SPE) and gradient HPLC
      separation is described. The analytical method was checked on intra- and inter
      day repeatability of the ethoxyresorufin-O-demethylation (EROD) reaction with CYP
      1Al/1A2 containing beta-NF induced rat liver microsomes as an enzyme source.
      These experiments showed that CYP activity was linearly decreased with 16% over
      an 11 h period. Inter-day measurements had a CV of 9.1%. Furthermore, Km and Vmax
      values of the EROD reaction, measured with the bioreactor, were 2.72 +/- 0.46
      microM and 7.9 +/- 0.5 nmol/min/mg protein, respectively. These were in good
      correspondence with Km and Vmax values, measured with standard batch assay, which
      amounted 0.66 +/- 0.08 microM and 6.4 +/- 0.2 nmol/min/mg protein respectively.
      In conclusion the newly developed analytical method can be used effectively and
      at a microliter scale for online generation, extraction and separation of
      metabolites.

PMID- 15974135
TI  - Supercritical fluid extraction of sinomenine from Sinomenium acutum (Thumb) Rehd
      et Wils.
AB  - Supercritical carbon dioxide, with and without a methanol modifier, was used to
      extract sinomenine from Sinomenium acutum (Thumb) Rehd et Wils. Sinomenine
      determinations were carried out using high-performance liquid chromatography
      (HPLC). The results show that the yield obtained after 2.5 h extraction with
      methanol-modified supercritical carbon dioxide was the highest (7.47 mg/g), while
      that obtained with only supercritical carbon dioxide was the lowest (0.17 mg/g).
      The recovery obtained with supercritical carbon dioxide, with and without a
      methanol modifier, could not be increased greatly by the method of the
      alkalinization of sample. Higher recoveries were obtained than extraction using
      methanol in Soxhlet extractor.

PMID- 15974136
TI  - Adolescents' health-related behaviors in the light of their value orientations.
AB  - This study examines the relationship between adolescents' health behaviors and
      their value orientations. Data were collected among a sample of Hungarian urban
      high school students (n = 602, aged 14-19; 52.8% males and 47.2% females) in
      2001. Factor analysis revealed fitness-oriented, health and social value
      oriented, and accomplishment/career oriented value factors. Health and social
      values were more common among girls, while accomplishment-oriented values were
      more common among boys. The fitness-oriented value orientation was related to
      physical activity and diet control, health and social value orientation showed
      significant association with diet control and the lack of smoking, alcohol and
      drug use, accomplishment oriented values were related to higher levels of
      substance use.

PMID- 15974137
TI  - Health care among insured drug users and nonusers.
AB  - This paper analyzes data on medical needs, utilization, and access collected
      during 1997-1999 in Houston from 117 drug users and 55 nonusers living in the
      same neighborhoods. Results indicate that drug users in Houston did not have a
      different level of medical needs than did nonusers, nor were they disadvantaged
      in terms of utilization or access to medical services. Part of the difference in
      results from previous studies may be because the longitudinal design of the study
      selected for relatively stable drug users and nonusers (for example, all study
      participants reported some form of publicly funded health insurance). Thus we
      suggest that, among persons with stable life situations, drug use does not
      significantly influence medical need, access, and utilization.

PMID- 15974138
TI  - The Action Plan--a new instrument to collect data on interventions in secondary
      prevention in adolescents.
AB  - It is difficult to draw causal conclusions about the effectiveness of secondary
      prevention programs for adolescents at risk, when the programs use a variety of
      different interventions. The Action Plan is an instrument that is designed to
      make collection of such data possible. This allows calculating different kinds of
      intervention patterns for each participant and program, which, in combination
      with outcome measures, gives an estimate of successful vs. less successful
      interventions. The study compared intervention patterns from 12 different sites
      in a national intervention program in Switzerland. The program, called supra-f
      (www.supra-f.ch), started in 1999 and will end in 2005. Results are presented
      from the ongoing study with approximately 600 adolescents. We calculated effect
      sizes (ES) to compare interventions with outcome measures. Effect sizes (ES) are
      presented on well being, coping, self-esteem, delinquency, and substance use
      (cigarettes, alcohol, cannabis) in relation to intervention packages, risk groups
      (low, moderate, high), and age (two groups: 11-15 and 16-20 years of age) using
      data collected from 1999-2002.

PMID- 15974139
TI  - Are questions from the Italian National Health Survey adequate to measure
      prevalence of smoking among teens.
AB  - OBJECTIVES: Studies on the prevalence of smoking among Italian adolescents have
      generated inconsistent estimates. Notably, the Italian National Health Survey
      (INHS) generates relatively lower estimates than estimates reported in other
      studies. The INHS asks adults and adolescents if they are smokers or nonsmokers.
      Research has shown that adolescent smoking is unstable compared to that of
      adults, and that adolescents may acquire their identity as smokers only after
      smoking becomes more established. We hypothesized that the INHS prevalence
      estimates of adolescent smoking could be improved by adding questions on smoking
      behavior. METHODS: During the school year 1993-1994, 471 participants responded
      to a brief survey on smoking experiences. We compared the prevalence of smoking
      behavior with the prevalence of smoking identity of participants (mean age =
      16.18) who attended five high schools in two Northern Italian cities, Padova and
      Bergamo. RESULTS: Measures of smoking behavior generated higher prevalence
      estimates than did measures of identity, particularly among occasional smokers.
      CONCLUSIONS: The INHS should add behavioral measures of smoking to maximize the
      accuracy of prevalence estimates.

PMID- 15974140
TI  - Revision of the Self-Administered Alcoholism Screening Test (SAAST-R): a pilot
      study.
AB  - The original Self-Administered Alcoholism Screening Test (SAAST; Swenson and
      Morse, 1975) is a self-report alcoholism screening measure intended for use with
      adult medical patients. However, the SAAST does not indicate the recency of
      alcohol use-related problems, not all items use the appropriate verb tense for
      assessing lifetime experience of alcohol use-related problems, many of the items
      contain out-dated language, and the diagnostic criteria for alcohol dependence
      and alcohol abuse are not fully represented. The SAAST was revised to address
      these issues. This paper describes the rationale for revision and the process
      through which the SAAST was revised. Preliminary information about comparability
      of the original SAAST and the revised version (SAAST-R) was obtained. Data are
      presented from two intervention trials for smokers in which both the SAAST and
      SAAST-R were administered. One sample was comprised of participants in recovery
      from alcoholism (N = 60; 82% male) and the other sample consisted of participants
      not meeting criteria for alcohol abuse or dependence within the previous year (N
      = 98; 45% male). The results suggest that the SAAST-R is highly correlated with
      the original SAAST, has a similar factor structure, good internal consistency,
      and correctly identifies those in recovery from alcoholism. Areas for refinement
      in the format and items of the SAAST-R were identified and suggestions for
      further validation studies are presented.

PMID- 15974141
TI  - Pilot study of the relationship between drug misuse and violence among drug
      addicts in Greater Accra, Ghana: the south of Saharan Africa case.
AB  - The purpose of this study is to explore the relationships between drug use/misuse
      and the prevalence of violence in sub-Saharan Africa. This study was undertaken
      as a pilot study to provide direction for a large-scale, systematic, countrywide
      or regional analysis. Hypotheses tested include the following: 1) drug use/misuse
      is related to violent behavior; 2) drug use/misuse is related to predatory
      violent behavior; and 3) drug use/misuse increases the likelihood that those
      addicted to drugs will commit violent acts. In order to test these hypotheses,
      two data sets were used to increase the robustness of the study. The first data
      set was collected during the summer of 1996, and was based on a self-reported
      survey of 117 subjects (17 women and 100 men), from different neighborhoods in
      Greater Accra and from different ethnic groups, mean age of 32, most were
      unemployed. The second data set was collected during the summer of 1997, based on
      a self-reported survey of 216 (45 women and 171 men) subjects from different
      neighborhoods in Greater Accra, from different ethnic groups, mean age of 31,
      most of whom were also unemployed. All hypotheses were confirmed by analysis of
      the data collected. This suggests that an expanded, countrywide study using the
      same procedures and instrumentation would provide a meaningful foundation for
      sound decisions by governmental officials and policy-makers in dealing with drug
      use and violence in Ghana. Further, the approach could serve as a model for other
      countries addressing similar problems.

PMID- 15974142
TI  - Suicidal ideation and alexithymia in patients with alcoholism: a pilot study.
AB  - OBJECTIVE: Suicidal incidences are known to be high in patients manifesting
      alcoholism. We attempted to characterize suicidal ideation in Japanese patients
      with alcoholism in relation to alexithymia. METHODS: Eighty-five male alcoholic
      patients, hospitalized in the alcoholics ward of a mental hospital and aged
      between 40 to 69 (52.9 +/- 8.3 years), and 79 nonalcoholic males in the same age
      range (54.9 +/- 7.1 years) recruited from a municipal garbage disposal plant were
      included in the study. The patients were evaluated using the Scale of Suicidal
      Ideation (SSI) and the Toronto Alexithymia Scale (TAS) during 2002. RESULTS: Of
      the alcoholic patients, 76.6% belonged to the high-risk group of suicidal
      ideation (SSI > 2), and 66.6% of the high-risk patients were alexithymic. In
      contrast, 86.1% of the nonalcoholic controls showed no suicidal ideation and only
      17.7% of those without suicidal ideation were alexithymic. When the alcoholic
      patients with intensive suicidal ideation were compared with nonalcoholic
      patients without suicidal ideation, the scores of factor 1 and factor 2 were
      significantly higher in the former group (p < 0.001). CONCLUSIONS: Alcoholic
      patients with intensive suicidal ideation accompanied with alexithymia are
      characterized by the inability to communicate feelings. Therefore, the
      possibility of a suicidal attempt in those patients should always be kept in mind
      even though no suicide message is expressed.

PMID- 15974143
TI  - Incarceration, addiction and harm reduction: inmates experience injecting drugs
      in prison.
AB  - Within Canadian prisons HIV/AIDS is becoming more common among inmates. While
      injection drug use in correctional facilities is documented to be a problem,
      qualitative research into the HIV risks faced by inmates is lacking. The goal of
      this research was to qualitatively examine HIV risk associated with injecting
      inside British Columbia prisons. A sample of 26 former male inmates who had
      recently used drugs within correctional facilities were recruited from a ongoing
      cohort study of injection drug users in Vancouver, Canada. Data for this study
      were collected through in-depth interviews conducted in 2001/2002. Analysis of
      these data involved identifying emergent themes and then exploring these central
      concepts in further interviews to confirm the accuracy of interpretation. The
      harms normally associated with drug addiction, and injection drug use are
      exacerbated in prison. Interpersonal relationships and the possession of
      exchangeable resources determine access to scarce syringes. The scarcity of
      syringes has resulted in patterns of sharing amongst large numbers of persons.
      Continual reuse of scarce syringes poses serious health hazards and bleach
      distribution is an inadequate solution. The findings of this study emphasize the
      need for effective harm reduction programs that provide an appropriate response
      to the problem of injection drug use among inmates.

PMID- 15974144
TI  - Promoting healthy choices: the importance of differentiating between ordinary and
      high risk cannabis use among high-school students.
AB  - Education can affect the lives of adolescents by reinforcing healthy choices and
      promoting a healthy lifestyle. However, difficulties experienced in the school
      and family environments may interfere with these goals. This may be particularly
      true for those youth already participating in health-compromising behaviors such
      as drug use. Of course, patterns of drug use take many forms, and some are more
      serious than others. Youth using cannabis at more intensive levels have often
      been overlooked in the literature. This paper, based on 1997 data, addressed this
      gap by examining the effects of individual and cumulative school and family
      factors on not only the probability of any cannabis use but also the progression
      to problem use among 1980 Ontario students. The results suggested that disrupted
      family structure increased the likelihood of cannabis use in general. However,
      patterns of problem use were displayed among youth experiencing problems in
      school and poor family relationships. As anticipated, adolescents experiencing
      multiple school and family factors were also significantly more likely to engage
      in cannabis use, and in its more serious form, when controlling for other
      demographic predictors. The implications for health promotion initiatives in the
      school are discussed.

PMID- 15974145
TI  - Dependence on cannabis--an ever lasting issue.
AB  - In this paper the dependence syndrome on cannabis as it is defined in
      International Classification Systems (e.g., DSM-IV) will be examined from a
      theoretical and a technical point of view. Therefore, both the conceptualization
      and the operationalization of the dependence syndrome are the focus of interest.
      It is shown that dependence on cannabis should deal with only psychic dependence.
      Analyzing criteria of psychic dependence via DSM-IV points to the need of
      conceptual reformulation. Deficiencies concerning variable validity and
      measurement conditions are pointed out. It is suggested, that the dependence
      syndrome on cannabis via international classification systems (e.g. DSM-IV)
      should be revised.

PMID- 15974146
TI  - Efficacy of a drug prevention CD-ROM intervention for adolescents.
AB  - The purpose of the present study was to examine the efficacy of a substance abuse
      preventive intervention using CD-ROM technology among adolescents in the sixth
      and seventh grades (12- to 13-years-old). The CD-ROM program used interactive
      audio and video content to teach social resistance skills, general personal and
      social competence skills, and normative education. Rates of substance-use
      behavior attitudes, knowledge, normative expectations, and related variables were
      examined. From approximately 23 schools, students (n = 123) were randomly
      assigned to either receive the CD-ROM preventive intervention (n = 61) or to
      serve as a control group (n = 62). Study participants were 50% male,
      predominantly white (75%), and 94% came from two-parent families. Self-report
      data were collected using a self-administered web-based survey. Findings
      indicated that there were significant intervention effects on pro-drug attitudes,
      normative expectations for peer and adult substance use, anxiety reduction
      skills, and relaxation skills knowledge, with intervention students reporting
      improved scores on these outcomes at the posttest relative to control students.
      Findings indicate that a substance abuse-preventive intervention derived from an
      effective, school-based prevention approach is efficacious when delivered using
      CD-ROM technology. Research is needed to determine potential differences in the
      efficacy of CD-ROM prevention tools delivered in schools compared to home
      settings.

PMID- 15974147
TI  - Pushing back the frontiers of science. Interview by Nick Lipley.

PMID- 15974148
TI  - Board's eye view.

PMID- 15974149
TI  - Breaking the silence.

PMID- 15974150
TI  - Emergency department use by people on low income.

PMID- 15974151
TI  - Streaming A&E patients to walk-in centre services.

PMID- 15974152
TI  - How emergency department nurses identify and respond to critical illness.

PMID- 15974153
TI  - Skills for life.

PMID- 15974154
TI  - Internet-based mental health interventions.
AB  - Following recent reviews of community- and practice-based mental health
      interventions, an assessment of Internet-based interventions is provided.
      Although relatively new, many Internet mental health interventions have reported
      early results that are promising. Both therapist-led as well as self-directed
      online therapies indicate significant alleviation of disorder-related
      symptomatology. The number of studies addressing child disorders lags behind
      those of adults. More research is needed to address methodological issues of
      Internet-based treatments.

PMID- 15974155
TI  - Employment outcomes and PTSD symptom severity.
AB  - A diagnosis of chronic war-related posttraumatic stress disorder (PTSD) has been
      linked consistently to poor employment outcomes. This study investigates the
      relation further, analyzing how symptom severity correlates with work status,
      occupation type, and earnings. Study participants were male Vietnam veterans with
      severe or very severe PTSD who received treatment in the Department of Veterans
      Affairs system (N = 325). Veterans with more severe symptoms were more likely to
      work part-time or not at all. Among workers, more severe symptoms were weakly
      associated with having a sales or clerical position. Conditional on employment
      and occupation category, there was no significant relation between PTSD symptom
      level and earnings. Alternative PTSD symptom measures produced similar results.
      Our findings suggest that even modest reductions in PTSD symptoms may lead to
      employment gains, even if the overall symptom level remains severe.

PMID- 15974157
TI  - Correlates of family contact with the mental health system: allocation of a
      scarce resource.
AB  - This study explored correlates of informal and formal contact between clinicians
      and families of individuals with schizophrenia. We reanalyzed data from 902
      individuals with schizophrenia from the Schizophrenia Patient Outcomes Research
      Team (PORT) client survey and a Veterans Affairs extension. Only 31% of families
      had any informal contact with a clinician and 7.8% attended a formal support
      program. Logistic regression showed that younger age, greater education, drug
      problems, receiving psychiatric inpatient and day treatment services, and
      participants' satisfaction with their family were all positively and
      significantly associated with informal contact. Receipt of formal family services
      was associated with intensity of social contact between participants and
      families. These results suggest that formal services for families of individuals
      with schizophrenia are not commonly available, and that informal pathways are the
      most common, although still limited, mechanism through which families of those
      patients who are receiving intensive services communicate with clinicians.

PMID- 15974158
TI  - The effects of race and criminal justice involvement on access to atypical
      antipsychotic medications among persons with schizophrenia.
AB  - This study examined the impact of race and arrest history on the likelihood of
      being prescribed, and maintaining an atypical antipsychotic prescription for 90
      or more days among patients with schizophrenia in the community. Participants
      were 224 adults with schizophrenia-spectrum disorders receiving services in
      public-sector mental health systems in North Carolina. The data used for this
      report were from a subsample of a larger group of participants being followed in
      an observational study and consisted of individuals who were prescribed either an
      atypical or conventional antipsychotic medication for 90 or more days. The
      purpose of the analyses presented here was to investigate differences in the
      likelihood of being prescribed an atypical antipsychotic by demographic and other
      characteristics. Logistic regression analysis indicated that African American
      patients were significantly less likely to receive atypical antipsychotics than
      their white counterparts, even when controlling for key clinical and demographic
      variables. However, white patients with a history of arrest were no more likely
      than black patients to receive atypical antipsychotics; that is, minority racial
      status and criminal involvement each functioned to limit patients' access to the
      novel medications. Implications for equal access to mental health services, in
      this case, effective psychopharmacologic treatment, are discussed.

PMID- 15974159
TI  - Payments by results: what does it mean?

PMID- 15974156
TI  - Clinical improvement associated with conformance to HEDIS-based depression care.
AB  - BACKGROUND: Employers recently requested a valid metric of depression treatment
      quality. Such an indicator needs to measure the proportion of the population in
      need who receive high-quality care, and to predict clinical improvement. METHODS:
      We constructed an administrative database indicator derived from HEDIS criteria
      for antidepressant medication management, and tested it in 230 employed patients
      in five health plans. RESULTS: Indicator rates were 7.0% in the population in
      need. Conformance to indicator criteria in this population was associated with
      23.0% improvement in depression severity over 1 year (p = .02). CONCLUSIONS:
      Administrative database indicators that predict clinical improvement are a very
      rare accomplishment. Existing depression indicators may need to be calculated for
      the population in need to provide a valid metric for employer purchasers.

PMID- 15974160
TI  - Hospital disciplinary procedures.

PMID- 15974161
TI  - Prevention and management of ureteric injuries.
AB  - Ureteric injury is one of the most serious complications of gynaecological
      surgery with important medico-legal considerations. This review is aimed at
      understanding the anatomy of the ureter, sites of ureteric injuries, types and
      causes of injury, simple preventive measures and management.

PMID- 15974162
TI  - Extranodal lymphoma: clinical presentation and diagnostic pitfalls.
AB  - Non-Hodgkin's lymphomas (NHL) are known to present extranodally in 25% of cases,
      in contrast to Hodgkin's disease which rarely involves extranodal sites. In this
      article, the authors will to review the presentation of extranodal head and neck
      NHL and the difficulties that can be encountered in making the diagnosis in these
      cases.

PMID- 15974163
TI  - Prevention of alcohol-related assault and injury.
AB  - There is a causal link between alcohol intoxication and injury in assault,
      mediated by individual, contextual and cultural factors. Harm reduction can be
      achieved through practical measures like plastic glasses and bottles in licensed
      premises, controlling drinks prices and targeted policing organized on the basis
      of police and accident and emergency data.

PMID- 15974164
TI  - Depression: diagnosis and management in terminal illness.
AB  - Depressive illness is often not recognized in terminally ill patients, because it
      is seen as an 'understandable' reaction. However, treating depression in such
      patients can significantly improve the quality of their remaining life. The
      diagnosis and management of depression in terminally ill patients will be
      discussed in this article.

PMID- 15974165
TI  - Heparin-induced thrombocytopenia.

PMID- 15974166
TI  - Structured clinical attachments for international medical graduates.
AB  - Clinical attachments are an opportunity for international medical graduates to
      gain some firsthand experience of the U.K. medical system and thereby improve
      their chances of finding employment. Unfortunately, these attachments may be hard
      to find and are of variable quality. This article details one deanery's approach
      to developing structured clinical attachments.

PMID- 15974168
TI  - Assisted reproductive technology: 25 years of progress.
AB  - Great strides have been made in assisted reproductive technology and nearly all
      forms of subfertility are now amenable to treatment. Constant advances in
      technology and ethical controversy ensure it has a high public profile. The
      impact of assisted reproductive technology will be discussed in this article.

PMID- 15974169
TI  - The first parathyroidectomy.

PMID- 15974170
TI  - Anabolic steroid-induced rhabdomyolysis.

PMID- 15974171
TI  - Large granular lymphocyte leukaemia: a curable form of pulmonary arterial
      hypertension [corrected].

PMID- 15974172
TI  - Nicotine replacement therapy and ischaemic stroke.

PMID- 15974173
TI  - A case of neonatal testicular torsion.

PMID- 15974174
TI  - An unusual complication of temporary pacing wire insertion.

PMID- 15974175
TI  - Mobile phones can be a pain--text messaging tenosynovitis.

PMID- 15974176
TI  - Is the move to the routine use of small endotracheal tubes evidence based?

PMID- 15974177
TI  - Biocompatibility of alginate.

PMID- 15974178
TI  - Bone marrow stromal cells differentiated into functional Schwann cells in injured
      rats sciatic nerve.
AB  - Bone marrow stromal cells (MSCs) have been shown to differentiate into various
      lineage cells including neural cells in vitro and in vivo. We therefore examined
      whether MSCs can differentiate into Schwann cells in injured peripheral nerves,
      After cultured in vitro, PKH-67-labeled MSCs were injected into the mechanically
      injured rat sciatic nerves. Three weeks after injection, immunofluorescent
      examinations were carried out. MSCs had been incorporated around the injured
      nerves and differentiated into Schwann cells. MSCs had accumulated mainly in the
      epineurium around the injured nerve. The incorporated cells partially expressed
      GFAP, S-100, and P75. These results confirmed the possibility that MSCs have the
      ability to differentiate into Schwann cells, and that injection of MSCs into the
      injured peripheral nerve would help repair damaged nerve.

PMID- 15974179
TI  - Extracorporeal whole blood immunoadsorption of autoimmune myasthenia gravis by
      cellulose tryptophan adsorbent.
AB  - Whole blood immunoadsorption (WBIA) system, using an adsorbent to remove
      pathogenic antibodies of myasthenia gravis (MG), was studied. Cellulose
      tryptophan adsorbent was synthesized and its adsorption capacity of binding with
      acetylcholine receptor in the plasma of MG patient was evaluated. Experimental
      autoimmune myasthenia gravis (EAMG) rabbits were induced by Ta183-200 peptide.
      The rabbits underwent extracorporeal whole blood adsorption for 2 h. Results
      showed no significant damages on blood cells and no changes in the concentration
      of electrolytes. Total protein decreased by 12.0% (P < 0.05), and globulin
      protein decreased 23.9 +/- 5.6% (P < 0.05). The mean overall removal of
      antibodies against Ta183-200 was 41.12%. The percentage of decrement of compound
      muscle action potential in 3, 5, 10Hz of EAMG rabbits all dropped down after the
      treatment. In conclusion, the adsorbent is biocompatible, was safe for whole
      blood immunoadsorption, and can remove antibodies in an MG patient effectively.
      Whole blood immunoadsorption improved clinical manifestation and neuromuscular
      function of the EAMG rabbits.

PMID- 15974180
TI  - High-porosity activated carbon as a possible matrix for native DNA and dextran
      sulfate immobilization.
AB  - In this study, specific and nonspecific activity of calf thymus DNA and Dextran
      Sulfate (DS)-containing synthetic carbonic adsorbents (0.7-7mg of each ligands
      per 1 cm3 of activated carbonic beads, 0.3-0.6mm diameter, bulk density gamma=0.1
      0.2g/cm3) have been compared in stir-bath and micro-column in vitro tests. DS
      coating as well as DNA coating does not demonstrate deep influence on the
      unspecific adsorptive activity of carbonic matrix toward creatinine, vitamin B12,
      and unconjugated bilirubin. No essential difference has been found in the
      specific activity of DNA and DS containing adsorbents toward anti-ds- and anti-ss
      DNA-antibodies, as well as antibodies against DNA-protein complexes (anti-DNP
      antibodies): in both cases the percentage of decrease of appropriate antibody
      concentration varied between 35 and 51% for single-pass microcolumn experiments
      with moderate enhancement of extraction efficacy (up to 60-75%) due to additional
      recirculation (2 h) or preliminary plasma dilution in 2-5 times. In the micro
      column experiments with the proinflammatory cytokines DNA or DS-coating did not
      diminish TNF-alpha, IL-1beta, and IL-6 adsorption from 3% BSA solution, but even
      improves to some extent its removal compared with uncoated matrix.

PMID- 15974181
TI  - Membrane for immunoisolation--properties before, and post implantation:
      preliminary report.
AB  - The membranes preventing tissue overgrowth as well as toxic influence on cells
      encapsulated within can be obtained modifying the polypropylene membranes by
      silanization. The influence of the silanization with different siloxanes on
      membrane transport properties was assessed before and post implantation. No
      change in cut-off values was observed. All of the modified membranes delayed
      tissue overgrowth of implant in mouse. Spectroscopic evaluation of the membrane
      material after 4, 7 days, 2 and 4 months of implantation revealed membrane
      material stability. We concluded that evaluated membranes with cells encapsulated
      within may be applied as the systems for delivery of biologically active
      substances.

PMID- 15974182
TI  - Starch-hemoglobin induces contraction on isolated rat aortic rings.
AB  - BACKGROUND: Blood substitutes are being developed using molecular solutions of
      modified free hemoglobin; however, anaphylactic reactions, severe renal toxicity,
      and hypertension have been reported in experimental models and human beings.
      Hypertension remains as an obstacle to the clinical use of most blood
      substitutes. Several investigators suggest that this effect is due to the
      interaction between nitric oxide and hemoglobin into the endothelial cells;
      hence, prevention of hemoglobin extravasation would avoid vasoconstriction. The
      forms of hemoglobin likely to prevent extravasation include polymerized and
      encapsulated Hb. Another alternative and significantly less expensive approach is
      the hydroxyethyl starch Hb-polymer. The aim of the present study was to compare
      the effect of hydroxyethyl-starch-hemoglobin with that of stroma-free hemoglobin
      on the in vitro contractile activity of aortic rings isolated from adult male
      rats. METHODS: The hemoglobin-based oxygen carrier was made using stroma-free
      hemoglobin prepared from outdated human red cells and conjugated with 10%
      hydroxyethyl starch 200-260 MW. The experiments were made in thoracic segments of
      the aortic rings incubated with hemoglobin, starch-hemoglobin or Ringer Krebs
      Bicarbonate solution (RKB) during 30 min. Smooth muscle contraction with
      phenylephrine and subsequent inhibition of contraction with carbachol were
      performed before and after incubation with hemoglobin, starch-hemoglobin, or
      vehicle. RESULTS: Incubation with hemoglobin and starch-hemoglobin significantly
      increased the contractile response to phenylephrine of aortic rings compared with
      RKB solution. The maximal response to carbachol was significantly decreased in
      the aortic rings incubated with either hemoglobin or starch-hemoglobin in
      comparison with the RKB-incubated tissues. There were no differences between the
      aortic rings incubated with either hemoglobin, or starch-hemoglobin. CONCLUSIONS:
      These results show that there are no differences between the effects of stroma
      free hemoglobin and starch-hemoglobin on the in vitro contractile activity of
      aortic rings isolated from adult male rats. Our findings do not support the
      hypothesis that an increase in the size of the hemoglobin molecule prevents
      hemoglobin extravasation, and the consequent vasoconstriction due to the
      scavenging of nitric oxide by stroma free hemoglobin in the cellular space
      between endothelium and smooth muscle.

PMID- 15974183
TI  - A novel carrier for Phanerochaete chrysosporium immobilization.
AB  - Phanerochaete chrysosporium BKMF-1767 cells were immobilized on different
      carriers. The optimum carrier according to adsorbed P. chrysosporium cells number
      (86.38%) was determined to be polystyrene foam, a novel carrier. The conditions
      for the immobilization of cells on polystyrene foam were optimized and determined
      as 50 rpm, 37 degrees C, and 2h. The results show that the adsorption of P.
      chrysosporium on polystyrene foam follows the Langmuir adsorption isotherm. High
      manganese peroxidase activity (421 U/L) and dry mass (4.7 g/L) were recovered
      from the batch mode polystyrene foam solid state fermentation system.

PMID- 15974184
TI  - Synthesis, characterization, biodegradation, and drug delivery application of
      biodegradable lactic/glycolic acid polymers: Part III. Drug delivery application.
AB  - Lactic/glycolic acid polymers (PLGA) are widely used for drug delivery systems.
      The microsphere formulation is the most interesting dosage form of the PLGA-based
      controlled release devices. In this study, the previously reported PLGA were used
      to prepare drug-containing microspheres. Progesterone was used as a model drug.
      The progesterone microspheres were prepared from PLGA having varied compositions
      and varied molecular weight. The microscopic characterization shows that the
      microspheres are spherical, nonaggregated particles. The progesterone-containing
      PLGA microspheres possess a Gaussian size distribution, having average size from
      70-134 microm. A solvent extraction method was employed to prepare the
      microspheres. The microencapsulation method used in this study has high drug
      encapsulation efficiency. The progesterone release from the PLGA microspheres and
      the factors affecting the drug release were studied. The release of progesterone
      from the PLGA microspheres is affected by the properties of the polymer used. The
      drug release is more rapid from the microspheres prepared using the PLGA having
      higher fraction of glycolic acid moiety. The drug release from the microspheres
      composed of higher molecular weight PLGA is faster. The drug content in
      microspheres also has an effect on the drug release. Higher progesterone content
      in microspheres yields a quicker initial burst release of the drug.

PMID- 15974185
TI  - The toxicological study of CCNU controlled release film in vivo.
AB  - We planted the Lomustine (CCNU) controlled release films into normal mice, and
      after a period of time observed the effects of the films on the blood cells and
      the brain nerve cells of the mice. Compared with the traditional administration
      (PO), the results indicated that the planted CCNU controlled release film had
      less effects on the blood cells, and caused less harm to the brain nerve cells.
      So the conclusion was that the planted CCNU controlled release film had no
      significant acute arrest of bone marrow and neural toxicity.

PMID- 15974186
TI  - Covalent attachment of oligonucleotides to cellulose acetate membranes.
AB  - During the last decade, DNA has become an increasingly important biomolecule in
      several areas. DNA technology has found many applications, e.g., in forensic
      science, environmental studies, diagnosis and archeometry. DNA microarrays and
      DNA biosensors applying the principle of immobilization of oligonucleotide on
      solid supports are used in these areas. DNA immobilization can be performed by
      adsorption and covalent attachment. In this study cellulose acetate was used as a
      solid support for oligonucleotide immobilization. Cellulose acetate was activated
      with 1,1'-Carbonyldiimidazole (CDI) and then coupled with 1,6-hexanediamine (HDA)
      as a linker. A hexadecadesoxy oligonucleotide was also activated by I-ethyl-3-(3
      dimethylaminopropyl) carbodiimide (EDC) and immobilized on the membrane by
      coupling via amino groups. The effects of various parameters on the
      immobilization oligonucleotide were investigated.

PMID- 15974187
TI  - Dismutation properties of purified and GDA modified CuZnSOD from chicken heart.
AB  - Superoxide dismutase (SOD, 1.15.1.1) from chicken heart has been purified 139
      fold with specific activity of 2130 IU/mg. Purified SOD has a molecular weight
      31.0 +/- 1.0 kDa and is composed of two equally sized subunits each having 1.1 +/
      0.03 and 0.97 +/- 0.02 atoms of Cu and Zn elements, respectively. Purified
      CuZnSOD modified by covalent attachment of the glutaraldehyde (GDA) in presence
      and absence of bovine serum albumin (BSA). The optimum conditions were obtained
      with a series of modification reactions as 0.25 mg/mL CuZnSOD in 50 mM phosphate
      buffer, pH 7.5 containing 3% GDA in presence and absence of 0.25 mg/mL BSA. The
      highest recovery activity of modified SODs was determined as 23.4 and 18.5% for
      the designated SOD-I and SOD-II derivatives, respectively. The recovery activity
      of SOD-I reached 28.6% while SOD-II didn't change significantly and determined as
      19% after the reaction with 1% ethylendiamine. The activity variations of native
      and modified CuZnSODs were investigated depending on the pH and temperature.
      Optimum pH values for native and modified SOD-I, -II were determined as 8.8, 8.3,
      and 8.2, respectively. The native and modified SODs have the same optimum
      temperatures approximately as 35 degrees C. The pH- and thermal-stability
      properties of modified SODs were found to be better than native SOD, in the pH
      range of 6.5-8.5 at 25 degrees C after 6 h, and up to 40 degrees C at pH 7.4
      after 3 h incubation period. Inhibitory effects of ditiothreitol (DTT), beta
      mercaptoethanol, and iodoacetamide were not observed on the native and modified
      SODs activities after 5 h incubation period. Phenylmethylsulfonylfloride (PMSF),
      H20O2, and EDTA were caused by slight inhibition on the enzyme activities.

PMID- 15974188
TI  - Preparation and properties of lipases immobilized on different supports.
AB  - Porcine pancreatic lipase and Candida cylindracea lipase were immobilized on
      Celite and Amberlite IRA-938. Activities and stabilities of immobilized lipases
      were investigated. The immobilized lipase derivatives on Celite exhibited grater
      residual activity and more resistance to thermal inactivation than their
      immobilized counterpart on Amberlite IRA-938. The apparent optimum temperatures
      of the immobilized lipases were 7-10 degrees C higher than that of the free
      enzymes. The native lipase and lipases immobilized on Celite showed same
      behaviors of pH dependence. But the pH optimum values for lipases immobilized on
      Amberlite IRA-938 were shifted to the acidic region relative to that of free
      enzymes. The stabilities of free and immobilized lipases were also investigated.

PMID- 15974189
TI  - A novel amperometric biosensor based on artichoke (Cynara scolymus L.) tissue
      homogenate immobilized in gelatin for hydrogen peroxide detection.
AB  - A biosensor for specific determination of hydrogen peroxide was developed by
      using homogenized artichoke (Cynara scolymus L.) tissue in combination with a
      dissolved oxygen probe and applied in determination of hydrogen peroxide in milk
      samples. Artichoke tissue, which has catalase activity, was immobilized with
      gelatine by means of glutaraldehyde and fixed on a pretreated teflon membrane.
      The electrode response was maximum when 0.05 M phosphate buffer was used at pH
      7.0 and at 30 degrees C. Upon addition of hydrogen peroxide, the electrode gives
      a linear response in a concentration range of 5.0-50 x 10(-5) M with a response
      time of 3 min. The method was also applied to the determination of hydrogen
      peroxide in milk samples.

PMID- 15974190
TI  - Let's get excited. Fun, therapeutic breaks for residents.

PMID- 15974191
TI  - At the nurses' station, improving data collection and care.

PMID- 15974192
TI  - Outlook solid for ALFs, CCRCs but not nursing homes.

PMID- 15974193
TI  - Recruiting from within: reducing burnout and turnover.

PMID- 15974194
TI  - Aging in place striking a delicate balance.

PMID- 15974195
TI  - Detailed analysis of DNBI (disease and non-battle injury) rates for ships within
      the US Fifth Fleet during 2000-2001.

PMID- 15974197
TI  - Increased evidence of testicular cancer among veterans of the 1991 Gulf War.

PMID- 15974198
TI  - Monitoring the health of Persian Gulf War veteran women. Federal Nursing Service
      Award.

PMID- 15974199
TI  - Soldier peer mentoring care and support: bringing psychological awareness to the
      front.
AB  - Since the Persian Gulf War of 1990-1991, the operational tempo for soldiers has
      steadily increased, whereas the numbers of soldiers available to fulfill these
      missions has decreased. As a result, soldiers and their families are experiencing
      increased levels of stress that continue to manifest in ways that can often be
      destructive for the soldiers, their families, and the Army community. Current
      mitigation and identification support systems such as the Chain of Command,
      noncommissioned officer leadership, chaplains, and family support systems have
      all provided critical services, but may not be expected to optimally perform
      necessary early risk management assessment. Behavioral health care as a self
      referral system is often still perceived as career ending, shameful, or even
      culturally unacceptable. Our allies have also experienced similar family,
      operational, and combat concerns. In 1996, at the direction of their Commandant
      General, the British Royal Marines developed and instituted a peer-driven risk
      management and support system that has experienced a high degree of success and
      acceptance among its forces-enough so that the Royal Navy is now in the process
      of implementing a similar program. The Soldier Peer Mentoring and Support
      program, as part of the proposed deployment Cycle Support Program, is a model for
      peer group assessment based on the British Royal Marines psychological risk
      management and support system. This article presents and describes this project,
      which has been considered for use within the U.S. Army, as a potential augmenter
      of existing behavioral health support assets as a culturally acceptable, company
      level support program in deployment and home stations.

PMID- 15974200
TI  - Developing military nursing research priorities.
AB  - Congress established the TriService Nursing Research Program (TSNRP) in 1992 to
      serve the nursing research needs of the military. The TSNRP advances the science
      of military nursing to support mission readiness and deployment, improves the
      health and quality of life of military personnel, and provides optimal nursing
      care in settings worldwide. In 1995, the TSNRP Advisory Council commissioned the
      Institute of Medicine to make recommendations on management, research funding
      areas, resource allocation, and objectives. In 1996, the committee issued its
      report, The Program for Research in Military Nursing: Progress and Future
      Direction. A principal recommendation was that the TSNRP hold regular research
      priority-setting conferences. In response, since 2000, the TSNRP has held three
      conferences. This article follows up the Institute of Medicine report and
      summarizes the results of those conferences. The article describes conference
      processes, constituents, and conclusions and outlines future TSNRP research
      directions.

PMID- 15974201
TI  - Measures undertaken in the German Armed Forces Field Hospital deployed in Kosovo
      to contain a potential outbreak of Crimean-Congo hemorrhagic fever.
AB  - During May and June 2001, the World Health Organization reported an outbreak of
      Crimean-Congo hemorrhagic fever in Kosovo. Two of the outbreak foci were located
      within the German Kosovo Force's zone of responsibility and thus countermeasures
      were undertaken at the German field hospital in Prizren to prepare for a
      potential outbreak among soldiers. A risk assessment was undertaken and the
      following essential issues were addressed: the education of troops with emphasis
      given to the prevention of tick bites, the establishment of an isolation unit,
      including barrier nursing and technical safety measures, the establishment of
      procedures for the safe handling of biological specimens intended for laboratory
      diagnosis, protocols for the treatment and prophylaxis with ribavirin, protocols
      for effective disinfection and decontamination, and an "outbreak plan" should the
      disease spread among soldiers. Using Army Mobile Field Hospital System equipment,
      a plan was implemented within 72 hours. The procedures described herein are
      likely to be suitable for the containment of other highly contagious diseases.

PMID- 15974202
TI  - Open access appointing in Army primary care clinics.
AB  - The open access model, also referred to as advanced or same-day appointments, is
      a new concept in managing patient appointments. More than 70% of the Army's
      primary care clinics currently use an antiquated system that inherently provides
      for a delay of medical services and lacks continuity of care. Although many
      providers and administrators believe delay and the lack of continuity of care are
      associated with a lack of resources, many studies prove otherwise. Open access is
      predicated on the principal that providers do today's work today. Patients
      calling to schedule an appointment with their provider are offered a same-day
      appointment. To achieve this, clinic chiefs and administrators must conduct an in
      depth analysis of their true demand and current resources. Clinic staffs who have
      a strong commitment to change will be able to convert to an open access model
      whereby they are able to increase patient and provider satisfaction.

PMID- 15974203
TI  - Trends in pleural radiographic findings in the Navy Asbestos Medical Surveillance
      Program (1990-1999).
AB  - The U.S. Navy Asbestos Medical Surveillance Program is a comprehensive effort to
      decrease exposure to asbestos, a known health hazard. This study was part of a
      programmatic review of the Asbestos Medical Surveillance Program database, which
      included 233,353 radiographic examinations from 1990 to 1999. The initial review
      focused on incidental findings recorded by B-readers for 23,460 radiographs.
      Abnormalities reported included bullae (0.68%), cancer (0.56%), cardiac size/
      shape abnormalities (1.36%), emphysema (0.74%), subpleural fat (2.62%), fractured
      ribs (1.24%), hilar adenopathy (0.13%), ill-defined diaphragm (0.46%), ill
      defined heart border (0.29%), Kerley lines (0.06%), pleural thickening (2.35%),
      and tuberculosis (0.27%). The rates by age cohort for pleural abnormalities
      decreased significantly (30-39 years, chi2 for trend = 23.49, df = 1; 40-49
      years, chi2 for trend = 176.21; 50-59 years, chi2 for trend = 401.87), but
      findings were not significantly different for those > or =60 years of age. This
      suggests that sequential age cohorts in the program are developing fewer pleural
      abnormalities; pleural abnormalities have historically been associated with
      asbestos exposure.

PMID- 15974204
TI  - Bradycardia-associated torsade de pointes and the long-QT syndromes: a case
      report and review of the literature.
AB  - We report a case of bradycardia-associated torsade de pointes in which the
      underlying long-QT syndrome appeared to be attributable to primary cardiac
      conducting system disease. Our patient presented complaining of presyncope and
      syncope. Serial electrocardiograms obtained over a period of 10 years
      demonstrated slowly progressive conduction system abnormalities, and evaluation
      revealed no other cause. The patient's dysrhythmia was refractory to magnesium
      but abated with cardiac pacing at a moderate rate. A review of the relevant
      literature on congenital and acquired long-QT syndrome is included.

PMID- 15974205
TI  - Aircraft carrier personnel mishap and injury rates during deployment.
AB  - This cohort study assessed all reported injuries experienced by the personnel of
      a U.S. Navy aircraft carrier during two consecutive 6-month deployments. These
      nondisease injury cases were collected by the ship's Safety Department from
      ship's Medical Department reports and showed 291 total injuries (3.05 injuries
      per 10,000 person-days) and 412 total injuries (4.39 injuries per 10,000 person
      days) among 5,101 personnel during two cruises, slightly higher than the
      recordable mishap rate for general U.S. industry (which uses a different metric).
      Junior personnel experienced one-half of the mishaps but represented only 31% of
      the manpower. Slips, trips, and falls were the most common causes of accidents on
      the ship, similar to general industry. The incidence densities and causes
      reported should be similar to and representative of those for other large deck
      ships in the U.S. Navy and can be used in developing risk-reduction strategies
      for targeted populations, to meet the Secretary of Defense requirement to reduce
      injuries by 50% in the next 2 years.

PMID- 15974206
TI  - Lessons learned: a successful distance learning collaborative between the
      Department of Veterans Affairs and the Department of Defense.
AB  - Academic, business, and government organizations are increasingly looking to
      distance education to meet workforce learning needs. This modality differs from
      classroom education, however, and simply transferring content from a traditional
      classroom to a distance learning application can result in poor outcomes. The
      Department of Veterans Affairs and the Uniformed Services University of the
      Health Sciences Graduate School of Nursing implemented a program preparing adult
      nurse practitioners solely through the medium of distance education, with no
      university "in-residence" requirement. Lessons learned from this success can
      prove useful to organizations that are planning distance education initiatives.

PMID- 15974207
TI  - Clinical outcomes of Gulf veterans' medical assessment programme referrals to
      specialized centers for Gulf veterans with post-traumatic stress disorder.
AB  - The study sought to ascertain whether referring veterans of the 1990-1991 Persian
      Gulf conflict with chronic post-traumatic stress disorder (PTSD) to specialized
      centers with a knowledge of military culture and the impact of conflict resulted
      in successful psychotherapeutic outcomes at 1-year follow-up times. A total of
      120 referrals to specialist centers were made by general physicians. Of these, 19
      were non-PTSD referrals, and 80 patients were confirmed by a psychiatrist as
      having PTSD. A degree of success in psychotherapeutic interventions for PTSD at 1
      year, determined from general practitioner follow-up correspondence, was obtained
      for 95% of referrals. There were no distinguishing features between successful
      and unsuccessful outcomes. This study shows that early attention, i.e., diagnosis
      and treatment by psychiatrists knowledgeable regarding the service environment,
      can be beneficial for this group.

PMID- 15974208
TI  - Postservice mortality of Air Force veterans occupationally exposed to herbicides
      during the Vietnam War: 20-year follow-up results.
AB  - Since 1982, the Air Force Health Study has continued to assess the mortality for
      veterans of Operation Ranch Hand, the unit responsible for aerially spraying
      herbicides in Vietnam. The mortality for 1,262 Ranch Hand veterans to December
      31, 1999 was contrasted with that for 19,078 comparison veterans. The relative
      risk (RR) for all-cause death was borderline significantly increased (RR, 1.15;
      95% confidence interval, 1.0-1.3; p = 0.06). The risk of death caused by cancer
      was not increased (RR = 1.0), but the risk of death caused by circulatory system
      diseases was significantly increased among enlisted ground crew workers (RR =
      1.7; 95% confidence interval, 1.2-2.4; p = 0.001). Results for Ranch Hand all
      cause death differed from previous reports, with the RR now exceeding 1.0. The
      risk of death attributable to circulatory system diseases continues to be
      increased, especially for enlisted ground crew, a subgroup with relatively high
      skin exposure to herbicides.

PMID- 15974209
TI  - Treatment of war injuries of the shoulder with external fixators.
AB  - In this retrospective study, 18 patients with war injuries of the shoulder were
      reviewed to evaluate the technical problems associated with external fixation and
      to analyze the incidence of infection and late functional results. The average
      patient age was 28.5 years. All patients were male. Thirteen patients had
      explosive wounds, whereas five wounds were caused by gunshot missiles. All
      injuries were extensive in terms of bone and soft tissue defects. Six patients
      presented with complex injuries involving neurovascular structures. Sixteen
      patients were treated with external fixation. Application of the proximal pins of
      the external fixator through the humeral head was possible in eight patients, the
      scapula served as the site of proximal fixation in four patients, only the
      clavicle was available for placement of pins in two patients, and both the
      scapula and the clavicle had to be pinned to achieve proximal stabilization in
      two patients. In two patients, fixation was not possible and early amputation was
      performed. Infection was eventually eradicated in all patients, allowing for
      adequate soft tissue coverage of the wounds. Analysis of functional results at an
      average of 6 years after the injury showed a considerable degree of functional
      deficit in most patients.

PMID- 15974210
TI  - Ipsilateral fibular transfer for a large tibial defect caused by a gunshot
      injury: case report.
AB  - Segmental bony defects in open fractures of the tibia are bridged with bone
      grafting, free vascularized fibular grafts, or an external ring fixator. A 33
      year-old man sustained a gunshot injury to his left leg, resulting in Gustillo
      type IIIB open fractures of the tibia and fibula. The tibia had a segmental
      massive defect of 19 cm in the midshaft. Debridement and immediate application of
      an Ilizarov external fixator were performed. The midportion of the ipsilateral
      fractured fibula served as a bridging vascularized graft for the tibial defect.
      Good bony union and fibular hypertrophy were obtained. Use of a fractured fibula
      from a zone previously injured by a gunshot has not been reported. This case
      demonstrates the successful transfer of a fractured fibula for the bridging of an
      ipsilateral tibial defect caused by a gunshot injury.

PMID- 15974211
TI  - Complications of missile craniocerebral injuries during the Croatian Homeland
      War.
AB  - OBJECTIVE: Complications of penetrating craniocerebral injuries in war can be
      early (during the first week after wounding) or late (after that period).
      Postoperative hematomas, infections, seizures, and cerebrospinal fluid fistulas
      (CSFFs) are counted among the early complications, whereas foreign bodies
      migrating intracranially, seizures, infections, and posttraumatic hydrocephalus
      represent late complications. A total of 176 patients with well-defined head
      injuries from missiles, sustained during the Croatian Homeland War (1991-1995),
      developed a total of 61 (34.5%) complications. METHODS: A retrospective
      statistical analysis of the medical records of the patients in our series was
      performed to determine the risk factors for the onset of complications, which
      have unfavorable effects on outcomes. RESULTS: There were a total of 28 (15.9%)
      infections (deep or superficial), 21 (11.9%) cases of CSFFs, 9 (5.11%) cases of
      early epilepsy, and 3 cases of post-traumatic hydrocephalus. A total of 47.6% of
      patients with CSFFs developed intracranial infections. Of eight patients with
      meningoencephalitis, five had CSFFs and four had intracranially retained foreign
      bodies. Only one patient developed a cerebral abscess. Two patients died because
      of infectious complications (13.3%). Post-traumatic hydrocephalus (1.7%) required
      shunt placement. For 60% of patients with deep-seated intracranial infectious
      complications and 76% of patients with CSFFs, reoperations had to be performed,
      whereas this was the case for only 8% of patients without infections (chi2 =
      43.6, p = 0.00001). CONCLUSIONS: Intracranially retained foreign bodies, wound
      age, wound site, and operations performed outside the neurosurgical services were
      the main risk factors for the development of complications. Complications
      themselves exerted a very unfavorable influence on outcomes. The development of
      complications reflects very reliably the neurosurgical technique applied.

PMID- 15974212
TI  - Israeli Army casualties in the second Palestinian uprising.
AB  - This study analyzes the pattern of injuries and evacuation in this unique low
      intensity conflict with many casualties and high availability of medical services
      and evacuation means. Injury data regarding Israel Defense Forces casualties
      during the first 19 weeks of the events were collected and analyzed. Ninety-six
      of the 356 Israel Defense Forces casualties during the first 4 months of the
      events were admitted or killed. Bullets (63.5%) were the most common cause of
      injury. Fragments and explosives accounted for 14.6% of injuries, stones and
      sling-thrown marbles accounted for 9.4% of injuries, and 12.5% of injuries were
      from miscellaneous causes. The most commonly injured body regions were the head,
      face, and neck (54.2%) and the limbs (50.0%). The trunk was injured in 25.0% of
      cases, and 4.2% of injuries were classified as external. Injury severity
      distribution was bimodal. The largest group represented patients with Injury
      Severity Scores (ISSs) between 1 and 14. The other large group was the 23 dead
      soldiers. The group of soldiers with ISSs between 16 and 75 included five
      patients only. Sixteen of the 23 dead soldiers were killed in action. Seven
      soldiers died of their wounds in the hospital, four of them within the first hour
      after admittance. A total of 83.8% of the casualties were evacuated by ambulances
      and the rest were evacuated by air. All casualties except one reached the
      hospital within 1.5 hour after the injury. Seventy-five percent of the injured
      were evacuated to trauma centers, and the rest were evacuated to other hospitals.
      The group of soldiers evacuated to trauma centers had a significantly (p = 0.021)
      higher mean ISS. The nature of this conflict resulted in a bimodal distribution
      of injuries. Most of the soldiers were either mildly injured or killed, whereas
      relatively few suffered severe injuries. The prehospital medical forces should be
      able to identify such patients and provide prompt treatment and evacuation. The
      abundance of head, face, neck, and limb injuries suggests that the current armor
      systems should be further investigated and improved.

PMID- 15974213
TI  - Acute coronary syndrome and the 1992-1995 war in Bosnia and Herzegovina: a 10
      year retrospective study.
AB  - OBJECTIVE: To examine the effects of war in Bosnia and Herzegovina on the
      occurrence of acute coronary syndrome among civilians. METHODS: The incidences of
      acute myocardial infarctions (first and recurrent) and unstable angina pectoris
      were examined among the residents of Mostar and the nine neighboring districts.
      The study population was the population that lived in the area before the war
      (182,000 in the 1991 census). Others who immigrated into the area were not taken
      into consideration. Five consecutive years (1987-1991) before the war and 5
      consecutive years (1992-1996) during the war were analyzed. RESULTS: In the 5
      year period during the war, 267 men and 161 women suffered from acute myocardial
      infarctions, compared with 246 men and 119 women in the 5-year period before the
      war. The wartime increase in acute myocardial infarctions for the combined male
      female population was statistically significant (p = 0.025). For women, the
      wartime increase was statistically significant only for the age group of 60 to 69
      years (p = 0.007). The smaller increase among men was not statistically
      significant (p = 0.354). The increase to a wartime number of 52 cases of
      recurrent myocardial infarctions from a prewar level of 24 was statistically
      significant (p = 0.001). The percentage of fatal myocardial infarctions among
      women, however, was lower during the war (18.6%) than before the war (32.8%) (p =
      0.048). During the war, 109 men with unstable angina pectoris were hospitalized,
      compared with 84 before the war; the cases among women were 76 and 41,
      respectively. The increase was statistically significant among women (p = 0.001)
      but not among men (p = 0.072). There was a statistically significant increase (p
      < 0.001) in the total number of unstable angina pectoris cases during the war
      (185 cases, compared with 125 prewar cases). CONCLUSION: The common population
      during the war in Bosnia and Herzegovina had increased numbers of acute
      myocardial infarctions and unstable angina pectoris cases.

PMID- 15974214
TI  - Comparison of breastfeeding rates among women delivering infants in military
      treatment facilities with and without lactation consultants.
AB  - Dedicated breastfeeding professionals improve breastfeeding initiation, which
      benefits infants, mothers, families, society, and the military. Research provides
      evidence that breastfeeding decreases rates of infection, hospitalization, and
      obesity, contributes to higher intelligence among breastfed infants, and reduces
      employee absenteeism and maternal breast cancer risk. This retrospective study
      examined the impact of lactation consultants (LCs) on breastfeeding initiation
      and continuation rates during the first 6 months of life. A sample set of charts
      for live infant deliveries between July 1, 2001 and September 30, 2001 at three
      southern U.S. military medical treatment facilities was reviewed. Ninety-eight
      percent (n=89) of mothers who interacted with the LC at the Air Force facility
      initiated breastfeeding, compared with 14.4% (n=3) of mothers without LC
      interaction (p < 0.001). Women with higher levels of education and those > or =27
      years of age had higher breastfeeding initiation and continuation rates.
      Significantly more active duty mothers stopped breastfeeding at 4 months,
      compared with non-active duty mothers (p = 0.038).

PMID- 15974215
TI  - The demonstration of pulmonary neuroendocrine cell hyperplasia with tumorlets in
      a patient with chronic cough and a history of multiple medical problems.
AB  - A 58-year-old woman presented with chronic cough felt to be multifactorial
      secondary to asthma, gastroesophageal reflux disease, and chronic sinusitis.
      Additional medical history included obstructive sleep apnea, type 2 diabetes, and
      hypertension. She had a 40- year history of tobacco use, but quit 10 years ago.
      Her examination was significant for obesity and cobble stoning of the oropharynx.
      Pulmonary function testing and arterial blood gases were unrevealing. Chest films
      were normal. High-resolution computed tomography revealed multiple focal
      lucencies in a mosaic pattern consistent with air trapping and small airways
      disease. Bronchoscopy revealed normal airways and a noninflammatory
      bronchoalveolar lavage. Transbronchial biopsies revealed inflammatory infiltrates
      of the peribronchiolar interstitium. Lung biopsy revealed pulmonary
      neuroendocrine cell hyperplasia with tumorlets that stained positive for
      neuroendocrine tissue. We present the case of a woman with chronic cough,
      multiple medical problems, and pulmonary neuroendocrine cell hyperplasia with
      tumorlets.

PMID- 15974216
TI  - Clinical evaluation of the anti-plaque effect of a commercial chewing gum.
AB  - OBJECTIVE: The objective of this research was to evaluate the dental plaque
      control effect of a chewing gum versus brushing with a dentifrice via four
      clinical studies. METHODOLOGY: Study 1 compared a commercial chewing gum (Colgate
      Dental Gum, CDG) with a water control after 24 hours post-brushing; Studies 2 and
      3 compared CDG to two different brands of commercially available fluoride
      dentifrices after 24 hours post-brushing; Study 4 examined the anti-plaque effect
      of CDG plus a regular fluoride dentifrice (Colgate Winterfresh Gel, CWG) versus
      brushing with CWG alone for five days. The 24-hour clinical tests employed the
      Modified Gingival Margin Plaque Index (MGMPI), while the Quigley-Hein Plaque
      Index (QHPI) was used for the five-day study. All studies utilized a randomized,
      crossover design with a one-week washout period, and were single-blinded to the
      clinical evaluator. RESULTS: In Study 1, the mean MGMPI score for CDG was
      significantly lower (p < 0.05) compared to the water control. In Studies 2 and 3,
      while brushing with regular fluoride dentifrices provided improved plaque control
      compared to CDG, the chewing gum alone with no tooth brushing delivered a plaque
      reduction 60% as effective as brushing with a fluoride dentifrice. In Study 4,
      the group using the combination of chewing with CDG and brushing with CWG
      provided a significantly lower (p < 0.05) mean QHPI score compared to the group
      using the dentifrice only, particularly on the hard-to-brush lingual surfaces.
      CONCLUSIONS: Four clinical studies demonstrated that CDG provides a plaque
      control benefit. The results suggest that chewing gum may serve as an effective
      oral hygiene device when brushing may not be possible and, additionally, that
      chewing gum may serve as an effective adjunct to brushing for enhanced oral
      health.

PMID- 15974217
TI  - Three laboratory assessments of a new triple-head toothbrush and the Oral-B 40
      toothbrush.
AB  - OBJECTIVE: The objective of this series of laboratory studies was to assess a new
      triple-head toothbrush, the DR BEST FreiKopf, compared to the Oral-B 40
      toothbrush, for interproximal access efficacy (IAE), gingival margin cleaning
      (GMC), and subgingival access (SA) as measures of toothbrush efficacy.
      METHODOLOGY: In each procedure, six toothbrushes of each product were tested four
      times for a total of twenty-four tests on each toothbrush design. In the IAE
      assay, the tooth brushing technique involved independent evaluations of each
      toothbrush in a vertical or horizontal brushing motion, tooth shapes simulating
      anterior and posterior teeth, and a brushing weight of 250 g. The brushing
      apparatus was set to brush 15 seconds at two strokes per second with a 50 mm
      stroke. In the GMC assay, the tooth brushing technique involved independent
      evaluations of each toothbrush in a horizontal brushing motion, tooth shapes
      simulating posterior teeth, and a brushing weight of 500 g. Simulated gingivae
      were prepared from self-curing dental acrylic. The brushing apparatus was set to
      brush for 60 seconds at two strokes per second with a 15 mm stroke. In the SA
      evaluations, the tooth shapes simulating posterior teeth were used, as well as a
      brushing weight of 500 g for 60 seconds at two strokes per second with a 15 mm
      stroke. All readings were measured with 3x magnification by one investigator.
      RESULTS: The mean IAE value on anterior and posterior tooth shapes, with vertical
      and horizontal brushing, and overall, was significantly (p < 0.001) higher for
      the triple-head toothbrush than for the Oral-B 40 toothbrush. In the GMC assay,
      the triple-head toothbrush had a significantly (p < 0.001) superior mean value
      compared to the Oral-B 40 product tested. In the SA study, the triple-head
      toothbrush was significantly (p < 0.001) superior compared to the Oral-B 40
      toothbrush product tested. CONCLUSIONS: The triple-head toothbrush has
      demonstrated superiority to a traditional flat-head toothbrush for access into
      interproximal areas, and for removing deposits from the gingival margin, as well
      as below the gumline, in these laboratory assays.

PMID- 15974218
TI  - A 180-day clinical investigation of the tooth whitening efficacy of a bleaching
      gel with added amorphous calcium phosphate.
AB  - OBJECTIVE: The purpose of this study was to determine if there are any
      significant long-term clinical benefits, or side effects, caused by the addition
      of amorphous calcium phosphate (ACP) to a professional, 16% peroxide bleaching
      gel. METHODOLOGY: This study examined the effect of bleaching gel with added ACP
      in a subset of subjects (n=27) from a previously published, short-term (n=50)
      study, in which two groups were assigned to use either an experimental ACP
      containing gel or a similar "control" gel. Both groups used the product for four
      hours (or overnight) daily for 14 days. In the present study, the long-term ACP
      effects on tooth color, gingival health, and three measures of dentinal
      hypersensitivity at post-treatment days +90 and +180 were assessed. RESULTS: In
      the previously published study, at day +five, the difference in tooth whitening
      efficacy (relative to baseline) between the test group and the control group was
      only 0.19 shades and was not statistically significant. In the present study, at
      day +90, the differences between the groups had almost doubled, and were
      calculated to be 0.34 shades (statistically different; t-test p = 0.002).
      Furthermore, at day +180, the differences had more than doubled again, with the
      ACP group subjects' teeth being 0.78 shades lighter than the control group's
      teeth (statistically different; t-test p = 0.002). Considered as a percentage, at
      day +180 the ACP group had retained nearly 10% more of their original whitening
      treatment result compared to control. There were no other significant differences
      found between the two groups. Tooth sensitivity, soft tissue health, and gingival
      health remained similar to baseline levels. CONCLUSIONS: This study demonstrated
      that the ACP product offers 10% better long-term (6-months) whitening efficacy
      than the traditional bleaching gel tested. The long-term safety of the product
      has also been demonstrated, as there were no adverse gingival or other effects
      seen at either day +90 or day +180.

PMID- 15974219
TI  - Brushing with a potassium nitrate dentifrice to reduce bleaching sensitivity.
AB  - OBJECTIVE: This research systematically evaluated the use of a clinically proven
      desensitizing dentifrice prior to a bleaching regimen in a randomized, multi
      center, parallel group, open label clinical study following Good Clinical
      Practice guidelines. METHODOLOGY: Fourteen dental offices in West Palm Beach,
      Florida participated in the study during April/May 2004. Fourteen days prior to
      bleaching, impressions and oral soft tissue assessments were performed, and
      patients were randomized to either a KNO3 plus fluoride dentifrice (Sensodyne
      Fresh Mint), or a standard fluoride dentifrice (Crest Regular), brushing 2x per
      day. On Day 14, patients returned to the dental office for their custom tray and
      the dispensation of a bleaching kit (Day White Excel 3; 9.5% hydrogen peroxide
      and KNO3). This was used daily according to the manufacturer's instructions for
      30 minutes, and normal oral hygiene continued to be performed using the assigned
      toothbrush and dentifrice, brushing 2x per day. At the end of each bleaching day,
      patients answered diary questions about the occurrence and intensity of
      sensitivity. At the conclusion of the 14-day bleaching period (Day 28), patients
      returned to their dental office for re-examination, returning all products and
      diaries. Within seven days of completing the study, patients answered a telephone
      patient satisfaction survey. RESULTS: A total of 202 patients in fourteen (14)
      dental offices completed all aspects of the study and were used for the analysis.
      The professionally dispensed bleaching product provided an improvement of
      approximately 4.4 Vita shades, regardless of whether it was used with the KNO3
      plus fluoride (Sensodyne) or a standard fluoride (Crest) dentifrice. The patient
      perception of increased sensitivity caused by the bleaching treatment was low but
      measurable. In the first week of the bleaching, significantly more patients using
      the KNO3 plus fluoride dentifrice were free from sensitivity (58%) than the
      standard fluoride dentifrice group (42%). During the 14-day bleaching treatment
      period, the KNO3 dentifrice patients experienced significantly more "sensitivity
      free days" (average = 10.1) compared to the standard fluoride dentifrice group
      (average = 8.6). CONCLUSION: The use of the KNO3 plus fluoride dentifrice
      (Sensodyne), two weeks prior to and throughout bleaching, may be a useful adjunct
      for the management of sensitivity caused by professionally dispensed bleaching
      products. With the bleaching-induced tooth sensitivity, those patients in the
      KNO3 plus fluoride toothpaste group were significantly more satisfied with their
      whitening experience and willing to repeat the bleaching treatment.

PMID- 15974220
TI  - Plaque removal using a battery-powered toothbrush compared to a manual
      toothbrush.
AB  - OBJECTIVE: To evaluate the effectiveness of battery-powered tooth brushing in
      removing plaque in Kuwaiti children. METHODOLOGY: The subjects were 30 boys, aged
      9-11 years. Prior to the start of the study, the children had never used a
      battery-powered toothbrush. At baseline, plaque accumulation was assessed for
      manual tooth brushing and battery-powered tooth brushing (Oral-B Kids battery
      powered). All subjects then used the battery-powered toothbrush for two weeks at
      home. Plaque accumulation was again assessed for both manual and battery-powered
      tooth brushing. Plaque accumulation was assessed using the Soparkar modification
      of the Quigley-Hein Plaque Index. Differences in pre- and post-tooth brushing
      plaque, and change from baseline, were the outcome measures evaluated. RESULTS:
      At baseline, there was no difference in plaque removal between battery-powered
      tooth brushing and manual tooth brushing, either in difference between pre- and
      post-tooth brushing plaque measures (p = 0.44) or in percentage change (p =
      0.51). After two weeks of use, there was a statistically significant difference
      in plaque removal between battery-powered tooth brushing and manual tooth
      brushing, both in the difference between pre- and post-tooth brushing plaque
      measures (p = 0.01) and in percentage change (p = 0.006). Mean plaque removal by
      manual tooth brushing was 0.97 +/- 0.45, and mean plaque removal by battery
      powered toothbrush was 1.23 +/- 0.56. Mean percentage change in plaque removal by
      manual tooth brushing was 33.5 +/- 16.05, and mean plaque removal by battery
      powered tooth brushing was 43.0 +/- 18.82, which represented a 9.5% improvement
      for battery-powered tooth brushing compared to manual tooth brushing. CONCLUSION:
      After two weeks use of a battery-powered toothbrush, the plaque removal was
      enhanced compared to baseline and to manual tooth brushing. Battery-powered tooth
      brushing also enhanced manual tooth brushing ability.

PMID- 15974221
TI  - Marginal microleakage around class V cavities restored with glass ceramic inserts
      of different coefficients of thermal expansion.
AB  - OBJECTIVE: Evaluate microleakage around Class V resin restorations restored with
      glass ceramic inserts of different coefficients of thermal expansion.
      METHODOLOGY: Sixty non-carious extracted human premolars (patient age range 12-20
      years) were randomly assigned to three groups. Standard Class V preparations were
      cut in the buccal surface using customized Cerana burs, size 3. Glass ceramic
      inserts from two manufacturers (Cerana and Beta-Quartz) were used to restore the
      cavities, and were luted with a hybrid, high-viscous composite (Tetric Ceram) and
      a bonding agent (Excite). A control group, without inserts, was bulk-filled with
      a hybrid, high-viscous composite (Tetric Ceram). In accordance with American
      Dental Association (ADA) guidelines, half the preparation was in enamel and half
      in dentine/cementum, and had a mesio-distal width of 3 mm, an occluso-gingival
      height of 3 mm, and a depth of 2 mm. All margins had butt joints. The teeth were
      thermocycled 4000 times between water baths held at 5 degrees C and 55 degrees C,
      and the specimens prepared and examined for microleakage using 2.0% Procion Red
      dye, buffered at pH 7 as a marker. RESULTS: Microleakage was significantly less
      around cavities restored with Cerana glass ceramic inserts than around cavities
      restored with Beta Quartz glass ceramic inserts or the control cavities at both
      the occlusal and gingival margins, p = 0.003 and p = 0.014, respectively.
      Comparisons of both occlusal and gingival margins within both test groups and the
      control group showed there was significantly less microleakage at the enamel
      resin interface than at the dentine-resin interface (p < 0.05 in all cases).
      CONCLUSION: The results strongly suggest that restorations restored with Cerana
      glass ceramic inserts, which have a coefficient of therml expansion approximating
      that of enamel, result in a decrease in marginal microleakage compared to Beta
      Quartz glass ceramic inserts and Tetric Ceram resin-based composite material.

PMID- 15974222
TI  - How many beans make ten?

PMID- 15974223
TI  - Time to move on.

PMID- 15974224
TI  - Making sense of job references.
AB  - Have you ever been asked to be a referee and write a reference for a work
      colleague? If it is a task you have not done before the prospect can be quite
      daunting: no one wants to give a bad reference and harm the prospects of a work
      colleague obtaining another employment post or even a promotion. Perhaps you are
      a manager or team leader that has experience of writing job references? But are
      you aware of the legal implications of writing a reference?

PMID- 15974225
TI  - The changing face of surgery: using systematic reviews.
AB  - Three systematic reviews relating to pre-admission procedures, admission
      procedures and staffing policies were undertaken to establish evidence to develop
      best practice guidelines for day surgery units. Results revealed that a pre
      admission intervention can improve patient and surgery outcomes, although the
      most effective type of intervention should be further investigated. It was also
      found that distraction can reduce patient preoperative anxiety, and there is no
      high quality evidence relating skill mix, staffing levels and desired health
      outcomes in day surgery units. Recommendations for areas of future research are
      presented.

PMID- 15974226
TI  - Theatre nursing in post-SARS Hong Kong.
AB  - On a recent visit to Hong Kong the author visited an operating theatre in an
      effort to explore the differences and similarities with the U.K. She found that
      SARS has had a profound influence upon both public behaviour and the healthcare
      system. The author found the visit interesting and educational and she encourages
      others to make similar visits as a way of exchanging ideas and maintaining
      optimal practice.

PMID- 15974227
TI  - Surgical equipment and materials left in patients.
AB  - This article seeks to examine the issue of lost equipment and materials left in
      patients and the assumptions that registered theatre practitioners make. The
      assumptions are highlighted using a tragic case study that relates to a young
      lady who died and what the subsequent post mortem revealed: five pieces of gauze
      in her abdominal cavity which were proved to be five surgical swabs. The problem
      of retained swabs and other surgical equipment is far greater than many would
      believe. It is said 'to err is human', but maybe to err is negligent.

PMID- 15974228
TI  - Building illness.

PMID- 15974229
TI  - If the boot camp fits.

PMID- 15974230
TI  - Nonalcoholic fatty liver disease in India--how much? How soon?

PMID- 15974231
TI  - Locoregional therapy for hepatocellular carcinoma.

PMID- 15974232
TI  - Recent advances in hepatorenal syndrome.
AB  - Hepatorenal syndrome is a common complication of advanced cirrhosis,
      characterized by renal failure and major disturbances in circulatory function.
      Renal failure is caused by intense vasoconstriction of the renal circulation. The
      syndrome is probably the final consequence of extreme underfilling of the
      arterial circulation secondary to arterial vasodilatation in the splanchninc
      vascular bed. The diagnosis of HRS is currently based on the exclusion of other
      causes of renal failure. The prognosis is very poor, particularly when there is
      rapidly progressive renal failure (type 1). Liver transplantation is the best
      option in patients without contraindications to the procedure, but it is not
      always possible owing to the short survival expectancy. Therapies introduced
      during the past few years, such a vasoconstrictor drugs (vasopressin analogues,
      mu-adrenergic agonist) or the transjugular intrahepatic portosystemic shunt, are
      effective in improving renal function. Nevertheless, liver transplantation should
      still be done in suitable patients even after improvement of renal function
      because the outcome of HRS is poor.

PMID- 15974233
TI  - Stem cells in medicine.

PMID- 15974234
TI  - A prospective epidemiological study to see if mosquito bite could be responsible
      for spread of hepatitis B virus infection.
AB  - India is a intermediate prevalence zone for hepatitis B virus (HBV) infection.
      Although mode of transmission of HBV is parenteral, a significant number of
      patients contract HBV without any such history, the so-called "sporadic" cases.
      It is postulated that mosquitoes or other arthropods like bedbugs may be involved
      in transmitting hepatitis B virus (HBV). We hypothesized that, should mosquitoes
      be responsible for the transmission of HBV, then the incidences of malaria and
      acute hepatitis due to HBV should show a linkage. We have therefore studied the
      frequencies of malaria and acute hepatitis B prospectively over three years to
      see any (a) seasonal changes in the frequencies of the two diseases and (b) any
      correlation between the seasonal frequencies of two diseases. This study was
      carried out at Gujrat research and Medical Institute, which is a busy general
      hospital. Frequencies of malaria and acute hepatitis B were monitored monthly,
      prospectively over a period of three years. Malaria was clearly a seasonal
      disease but no distinct peak for acute hepatitis B was documented. Correlation or
      Linkage between the frequencies of malaria and acute hepatitis B could not be
      documented to suggest that mosquito bite may be responsible for HBV transmission.

PMID- 15974235
TI  - Xanthogranulomatous cholecystitis: differentiation from associated gall bladder
      carcinoma.
AB  - Xanthogranulomatous cholecystitis (XGC) is a destructive form of chronic
      cholecystitis. In some patients it coexists with gall bladder carcinoma (GBC) and
      is often difficult to differentiate between the two. Present study was performed
      with an aim to identify differentiating features of XGC and those of XGC with
      associated Gall bladder carcinoma (XGC ass. GBC). A retrospective analysis of
      prospectively maintained data of 4800 cholecystectomies performed from January
      1988 to December 2003 was carried out. On histopathology 453 cholecystectomy
      specimens revealed XGC. These patients were divided into two groups, those with
      associated GBC (n=26) and those without GBC (n=427). Clinical, radiological and
      operative findings were compared in these two groups. P value of < 0.05 was
      considered statistically significant. The incidence of associated GBC in present
      series was 6%. XGC patients with associated GBC, at presentation were older than
      those with XGC alone and there was male preponderance. XGC patients with
      associated GBC were more likely to present with anorexia, weight loss, palpable
      lump and jaundice. Gall stones were present in majority of patients in both the
      groups. GB wall thickening, GB mass, enlarged abdominal lymph nodes may be found
      on imaging in both the groups but more so in patients with associated GBC. Both
      preoperative FNAC and peroperative FNAC/imprint cytology failed to reveal the
      associated GBC with XGC in some patients.

PMID- 15974236
TI  - Choledochal cysts in African infants: a report of 3 cases and a review of the
      literature.
AB  - Choledochal cysts are relatively rare and are an uncommon cause of cholestasis.
      Early diagnosis and prompt treatment can prevent complications such as
      cholangitis, cirrhosis and portal hypertension. This article reviews a rarely
      reported disease in Africans in whom only 3 cases were documented over the 18
      year period in Nigeria. The 3 cases were all females with ages between less than
      a month and 13 months at presentation. All presented with abdominal swelling with
      or without jaundice or acholic stools. The use of real-time ultrasonography
      antenatally and postnatally aided the diagnosis in our patients. Two of the
      patients presented and were operated and both made full recovery confirming the
      importance of early surgical intervention. The third patient died, and
      exemplified the consequences of delayed diagnosis and treatment which occur not
      uncommonly in developing countries mostly because of sparse and or expensive
      tertiary health care facilities.

PMID- 15974237
TI  - Partial recanalisation of hepatic veins in Budd-Chiari syndrome: a case report.

PMID- 15974238
TI  - Recurrent small bowel intussusceptions: an uncommon presentation of celiac
      disease in an Arab child.
AB  - Causes of recurrent bowel intussusception in infancy are rarely identified and
      uncommon causes such as gluten sensitive enteropathy are not well recognized. We
      report a 3 year-old Saudi girl who presented with small bowel intussusception,
      which was diagnosed by abdominal CT. Investigations for concomitant failure to
      thrive revealed celiac disease. Her small bowel intussusception resolved
      completely when she was placed on a gluten free diet.

PMID- 15974239
TI  - Laparoscopic intervention in resistant hepatosplenic tuberculosis presenting as
      pyrexia of unknown origin.
AB  - Hepatosplenic tuberculosis (HST), rarely encountered in surgical practice, is
      seen in-patients with disseminated tuberculosis. A 20-year-old female presenting
      with pyrexia of unknown origin (PUO) was subsequently diagnosed to have lymph
      nodal tuberculosis with involvement of liver and spleen. Despite anti
      tuberculosis treatment (ATT) for 3 months, clinical improvement did not occur and
      fever persisted. Laparoscopic splenectomy and drainage of the hepatic cold
      abscess were done with favorable results. Smear for acid fast bacilli (AFB),
      culture for Mycobacterium tuberculosis and histopathological examination (HPE)
      established the diagnosis of tuberculosis (TB).

PMID- 15974240
TI  - Effect on gallbladder function subsequent to truncal vagotomy and
      gastrojejunostomy for chronic duodenal ulcer.
AB  - The effect of truncal vagotomy on gallbladder function and on the incidence of
      lithogenesis has remained controversial. A prospective and retrospective
      investigational study was undertaken to evaluate the effect of truncal vagotomy
      and gastrojejunostomy on gallbladder function. The study included a total of 76
      patients and 77 controls. In Group I (Prospective group), 32 consecutive patients
      with chronic duodenal ulcer and gastric outlet obstruction undergoing truncal
      vagotomy and gastrojejunostomy were included. Group II included 25 age and gender
      matched controls (prospective group). Group III included 44 patients who had
      undergone truncal vagotomy and gastrojejunostomy 3 years or more prior to
      presentation (Retrospective group) and Group IV included 52 age and gender
      matched controls for the retrospective group. The patients in the prospective
      groups were followed up for a period of 1 year. An alkaline tide test was done in
      the prospective and retrospective group to assess for the completeness of
      vagotomy. Gallbladder contractile response to fatty meal and the presence of
      stones and sludge were noted in all the four groups by ultrasonography. There
      were 30 patients in the prospective group and 40 in the retrospective group after
      excluding patients with incomplete vagotomy. On ultrasound examination, there was
      no significant difference in the gallbladder volume and contractility of the
      study group when compared with the controls. Gallbladder sludge was found in 16
      to 25% of patients in the prospective group (group I) during follow up, where as
      similar finding was documented in 8% of the matched control (group II (P>0.1).
      However, in the retrospective (group III) 10% (4 out of 40) had calculi and 20%
      of patients demonstrated sludge which was significantly higher when compared with
      the controls (p = 0.001). Truncal vagotomy and gastrojejunostomy did not affect
      gallbladder contractility, but it might predispose to the formation of sludge and
      subsequent calculi in a proportion of patients in long term.

PMID- 15974241
TI  - Spontaneous appendico-cutaneous fistula--a rare complication of acute
      appendicitis.
AB  - Spontaneous Appendicocutaneous fistula (SACF) is a rare complication of acute
      perforating appendicitis. We describe one such case where the patient presented
      with a chronic discharging sinus in the right flank. Pathogenesis of this unusual
      lesion, its clinical presentation and the management are discussed and the
      literature reviewed. Preoperative diagnosis of this condition needs high index of
      suspicion. CT fistulogram is a valuable aid in this regard.

PMID- 15974242
TI  - The abdominal cocoon and an effective technique of surgical management.
AB  - The Abdominal Cocoon is a very rare cause of small bowel obstruction. It is
      caused by encapsulation of the small bowel by a fibrous membrane. This tropical
      disease, seen in young females, has also been reported in males. This is one of
      the largest series of the Abdominal Cocoon, with five new patients (3 males and 2
      females) being reported. The traditional surgical treatment of choice is by lysis
      of adhesions. All patients in this case series had small bowel intubation done in
      addition to adhesiolysis. Although small bowel intubation is an established
      procedure for various causes of recurrent small bowel obstruction, to our
      knowledge this is the first report of its use in the management of the Abdominal
      Cocoon. We report our surgical technique in the management of this rare disease.

PMID- 15974243
TI  - Parameters for measurement of oxidative stress in diabetes mellitus:
      applicability of enzyme-linked immunosorbent assay for clinical evaluation.
AB  - Investigations of the mechanisms involved in the onset and progression of
      diabetes have recently confronted the role of reactive oxygen species (ROS) and
      oxidative stress. Prolonged exposure to hyperglycemic conditions induces
      nonenzymatic glycation of protein via the so-called Maillard reaction, resulting
      in Schiff-base products and Amadori products that engender ROS production. These
      processes initiate and exacerbate micro- and macrovascular complications in
      diabetes. Increased oxidative stress is induced by excessive ROS production and
      inadequate antioxidant defenses. Recently, oxidative stress status markers have
      been associated directly with the severity and prognosis of diabetes. To examine
      oxidative stress, reliable and high-throughput methods are needed to examine
      large numbers of clinical samples. The emerging availability of enzyme-linked
      immunosorbent assay (ELISA) for oxidative stress status markers allows its
      application to assessment of various pathophysiologic conditions, including
      diabetes. This review outlines the recent achievements of ELISA application for
      clinical studies elucidating oxidative stress. It introduces the potential
      applicability of ELISA for investigating oxidative stress in diabetes.

PMID- 15974244
TI  - Radionuclide-based insights into the pathophysiology of ischemic heart disease:
      beyond diagnosis.
AB  - This review article discusses the historical origin of cardiac radionuclide-based
      methods, the physiologic background that justifies their existence, as well as
      the basic pathophysiologic concepts of coronary artery disease and their
      connection with the technologic design and application of these methods. Most
      importantly, this review discusses the important insights that these methods have
      provided to the understanding of the mechanisms of ischemia, risk stratification,
      and both treatment choice and treatment efficacy in ischemic heart disease.
      Nuclear cardiology originated as an attempt to provide complementary physiologic
      information to the anatomic information provided by coronary angiography. To
      comprehend the design and applications of nuclear cardiology methods, one must
      have a basic understanding of coronary artery disease as an inflammatory process
      that may manifest as acute or chronic states. Basic concepts on myocyte metabolic
      pathways, coronary blood flow, ischemic cascade, ventricular remodeling, and
      ejection fraction become critical for this purpose. Insights into risk
      stratification may permit patient-tailored therapy approaches. Insights into
      prognosis have made nuclear cardiology a robust tool for outcome predictions,
      with an exceptionally high negative predictive value. Evaluation of prognosis in
      special patient populations such as diabetics has originated important
      pathophysiologic concepts. Most insights into phenomena such as myocardial
      hibernation, myocardial stunning, and viability have been generated by nuclear
      cardiology techniques. Finally, new applications of radionuclide-based methods
      such as molecular identification of "vulnerable" atherosclerotic plaques,
      "ischemic memory" using fatty acid imaging, and myocardial innervation imaging
      provide new avenues for insightful research.

PMID- 15974245
TI  - Breaking the translational barriers: the value of integrating biomedical
      informatics and translational research.
AB  - The conduct of translational health research has become a vital national
      enterprise. However, multiple barriers prevent the effective translation of basic
      science discoveries into clinical and community practice. New information
      technology (IT) applications could help address these barriers. Unfortunately,
      owing to a combination of organizational, technical, and social factors, neither
      physician-investigators and research staff nor their clinical and community
      counterparts have harnessed such applications. Recently, at the request of the
      Institute of Medicine's Clinical Research Roundtable, a qualitative study of
      these factors was conducted at several leading academic medical centers. We
      explore the current status of IT in the translational research domain, describe
      the qualitative results, and conclude with a proposed set of initiatives to
      further increase the integration of IT into translational research.

PMID- 15974247
TI  - Hard facts.

PMID- 15974246
TI  - Host cells reduce glucose uptake and glycogen deposition in response to hepatic
      insulin gene therapy.
AB  - BACKGROUND: Hepatic insulin gene therapy (HIGT) restores weight gain and near
      normal glycemia in rodent models of insulin-deficient diabetes mellitus. However,
      the effect of transgenic insulin on endogenous genes and recipient cell function
      is relatively unexplored. To investigate hepatocellular effects of transgenic
      insulin expression, we evaluated intermediary glucose metabolism in primary
      cultured hepatocytes treated with HIGT. METHODS: Rat hepatocytes were transduced
      with adenovirus expressing a glucose-responsive human insulin transgene and
      cultured in high-glucose and high-insulin conditions. We determined glycogen
      content in cell cultures and intact liver directly. Glycogenolysis was compared
      using glucose production of cultured cells. Glucose uptake, oxidative, and
      glycolytic processing were determined by radiotracer analysis or direct end
      product assessment. Quantitative real-time reverse transcriptase polymerase chain
      reaction was used to determine expression of glucose transporter 2 (GLUT2) and
      glucokinase genes. GLUT2 protein abundance was determined by Western blot
      analysis. RESULTS: HIGT-treated hepatocytes contained significantly less glycogen
      than either untreated hepatocytes or those treated with an empty virus. Glucose
      release owing to glycogenolysis remained normal. However, HIGT treatment
      significantly impaired glucose uptake and processing. Metabolic synthetic
      processes were not generally inhibited, as indicated by enhanced beta
      hydroxybutyrate secretion. While preserving cell viability, HIGT treatment
      diminished expression of both glucokinase and GLUT2. In HIGT-treated streptozocin
      treated diabetic rats, total liver glycogen was intermediate between diabetic
      animals and normal controls. CONCLUSIONS: These results suggest gene-specific
      effects in recipient hepatocytes following HIGT treatment and underscore the need
      for expanded studies examining host cell responses to the transfer of
      metabolically active transgenes.

PMID- 15974248
TI  - Transcatheter ablation of supraventricular tachycardia and closure of a large
      secundum ASD in a Jehovah's Witness.
AB  - This report describes successful radiofrequency ablation of typical
      atrioventricular (AV) node reentrant tachycardiafollowed by transcatheter closure
      of a large secundum atrial septal defect in a patient of the Jehovah's Witness
      faith. Both procedures were performed successfully during the same
      catheterization, without complication or need for blood transfusion.

PMID- 15974249
TI  - Death certification: recording the correct terminology for accurate
      documentation.

PMID- 15974250
TI  - Wage & hour rules.

PMID- 15974251
TI  - 2005 KMA legislative report.

PMID- 15974252
TI  - We must make change.

PMID- 15974253
TI  - An allegory for our time.

PMID- 15974254
TI  - The sharpened Romberg test for assessing ataxia in mild acute mountain sickness.
AB  - OBJECTIVE: To evaluate the Sharpened Romberg Test (SRT) as a measure of ataxia in
      subjects with mild acute mountain sickness in order to determine its sensitivity
      and specificity. METHODS: The SRT was performed in 23 subjects during ascent to
      5260 m. RESULTS: The SRT was more often abnormal than the traditional heel-to-toe
      test, and at the highest altitude it was related to higher median Lake Louise
      symptom scores with predictive values of 60% sensitivity and 89% specificity. Our
      evaluation of the SRT appears to agree with similar studies on ataxia showing a
      lack of correlation between ataxia and symptoms of acute mountain sickness at
      altitudes below 5260 m. CONCLUSION: The SRT was easy to perform and provided a
      quantitative assessment of truncal ataxia in the field without the need for
      specialized equipment.

PMID- 15974255
TI  - Animal-related fatalities in the United States-an update.
AB  - OBJECTIVE: To evaluate the causes of human fatalities in the United States from
      1991 to 2001 that were caused by venomous and nonvenomous animal encounters
      exclusive of zoonotic infections or animal-vehicle collisions. METHODS: An
      inquiry of CDC Wonder, a database for epidemiologic research, was used to provide
      information on animal-related fatalities on the basis of ICD-9 and ICD-10 codes.
      RESULTS: From 1991 to 2001, 1943 persons died in the United States after venomous
      and non-venomous animal encounters. An average of 177 fatalities per year were
      recorded. Venomous animal encounters were responsible for 39% of the fatalities.
      White males appear to be the group most likely to die from an encounter. Most
      fatalities occurred in the southern United States. CONCLUSIONS: Although the
      average number of fatalities from animal encounters has increased compared with
      the previous decade, the death rate has remained essentially unchanged. The
      medical and financial costs from both fatal and nonfatal animal encounters have a
      significant impact on public health.

PMID- 15974256
TI  - Perceptions of surfboard riders regarding the need for protective headgear.
AB  - OBJECTIVE: To examine the use of protective headgear by surfers, their
      perceptions of its usefulness, and barriers to its use. METHODS: A researcher
      administered questionnaire was used to undertake a cross-sectional survey of 646
      surfboard riders at 8 popular surfing beaches in Victoria, Australia. The main
      outcome measures were rate of use of headgear, perceptions of head injury risk
      relative to a range of other activities, perceptions regarding headgear, and the
      reasons for not wearing headgear. RESULTS: Most surfers were men (90.2%), young
      (mean age 28.2 years), and experienced (mean years of surfing 11.6). Only 245
      (38.0%, 95% CI 34.2-41.9) surfers considered the risk of head injury while
      surfing as moderate or high, and only 12 (1.9%, 95% CI 1.0-3.3) reported routine
      use of headgear. The surfers were more likely to believe that there was a higher
      risk of head injury in other sports and physical activities (P < .001). Although
      475 surfers (73.8%, 95% CI 70.2-77.1) thought that surfers who wear headgear are
      less likely to become injured, 400 (62.1%, 95% CI 58.2-65.9) reported that
      headgear restricted surfing performance and that they would rather surf without
      it. The main reasons for not wearing headgear were "no need," discomfort,
      claustrophobia, and effects upon the senses and balance. CONCLUSIONS: Although
      most surfers acknowledge some risk of head injury, headgear is rarely used and
      barriers to its use are apparent. Research is required to clarify the risk of
      head injury among surfers and the effectiveness of headgear in reducing injury
      risk. Until this evidence is available, educational initiatives, improved
      headgear design, and profile within the surfing culture would be required to
      increase rates of wearing headgear.

PMID- 15974257
TI  - Autonomic nervous system and adrenal response to cold in man at Antarctica.
AB  - OBJECTIVE: To evaluate the role of the autonomic nervous system and adrenal
      system in acclimatization to cold in tropical men during short or prolonged
      sojourns at Antarctica. METHODS: The study was carried out on volunteers of the
      18th winter over team (WOT) and 19th summer team (ST) of an Indian Antarctic
      Expedition. The ST members were evaluated at Delhi; during voyage; and on days 7,
      30, and 60 of their stay at Antarctica. Identical studies were performed in WOT
      members who had stayed at Antarctica for 14 months. The parameters examined
      included heart rate, blood pressure, oral temperature, index finger skin
      temperature, heart rate variability, urinary epinephrine and norepinephrine, and
      salivary cortisol. RESULTS: The resting heart rate and blood pressure in ST
      members significantly increased (P < .05) on days 7 and 30 of their stay at
      Antarctica and returned to baseline Delhi values by day 60. The index finger
      temperature declined (P < .05) on day 7 at Antarctica and remained at lower
      levels during the entire period of observations. Heart rate variability showed an
      imbalance of autonomic nervous system effects with predominance of low-frequency
      band on day 7 of stay and returned to Delhi values by day 60. The urinary
      excretion of epinephrine and norepinephrine and salivary cortisol were also
      increased on day 7 and declined to baseline Delhi values after 2 months of stay.
      Compared with the ST group, the WOT group showed a significantly higher (P < .05)
      resting heart rate, blood pressure, and low-frequency power and urinary excretion
      of norepinephrine. CONCLUSIONS: These observations suggest that Antarctic
      residency during austral summer results in gradual attenuation of sympathetic
      tone and a shift of autonomic balance toward the parasympathetic side. However,
      WOT members showed a predominance of sympathetic and adrenal activity compared
      with initial responses of ST members, suggesting deconditioning or possible
      resetting of the autonomic nervous system.

PMID- 15974258
TI  - Gastroenteritis outbreak among mountaineers climbing the West Buttress route of
      Denali - Denali National Park, Alaska, June 2002.
AB  - OBJECTIVE: To determine the burden of and risk factors for diarrheal illness
      among mountaineers climbing Denali during the spring of 2002. METHODS: We
      conducted a retrospective cohort study of all willing and available climbers who
      returned to base camp from June 11 to 14, 2002. We used a questionnaire that
      addressed illness status, demographics, and potential risk factors for illness. A
      case of diarrhea was defined as self-reported diarrhea (loose stool) in a Denali
      climber who did not have diarrhea before arrival at base camp. RESULTS: Thirty
      eight (29%) of the 132 climbers who were interviewed reported experiencing
      diarrhea at some point on the mountain. Spending 8 or more days at the 17 200
      foot high camp; being a member of a climbing party in which at least 1 other
      person also had diarrhea, especially if tent occupancy was 3 or more; and not
      receiving education about disease risk-reduction techniques among climbers who
      were on a guided expedition were associated with increased risk of illness.
      CONCLUSIONS: To prevent infectious diarrheal outbreaks among mountaineers
      climbing Denali (and other highly trafficked alpine routes), we recommend that
      park staff provide climbers with detailed information related to minimizing
      disease risk and develop more effective strategies for preventing climbers from
      depositing fecal material directly into snow along the route, such as
      establishing and enforcing firmer penalties for noncompliance with existing human
      waste disposal regulations and requiring the use of personal stool-hauling
      devices.

PMID- 15974259
TI  - A fatal attack caused by a lowland tapir (Tapirus terrestris) in southeastern
      Brazil.
AB  - A 55-year-old man was attacked by a Brazilian tapir (Tapirus terrestris) after
      surprising and stabbing the animal in his corn plantation. The victim received
      deep bites in the thighs, neck, and cervical areas, resulting in severe
      hemorrhage and death. This is the first report of a tapir incident resulting in
      death and is of interest because of the severity of the contusions and
      lacerations caused by the provoked animal.

PMID- 15974260
TI  - Efficient breathing circuit for use at altitude.
AB  - We describe a case report of a subject suffering high-altitude cerebral and
      pulmonary edema successfully treated with low flow rates of supplemental oxygen
      administered with a breathing system designed to conserve oxygen supplies at high
      altitude.

PMID- 15974261
TI  - The perceived benefits of a medical school course in wilderness medicine.

PMID- 15974262
TI  - Amebic liver abcess in Nepal.

PMID- 15974263
TI  - Myokymia after snake envenomation in Arizona.

PMID- 15974264
TI  - Dysphonia: a new addition to jellyfish envenomation syndromes.

PMID- 15974265
TI  - Dairy manure nutrient analysis using quick tests.
AB  - Rapid on-farm assessment of manure nutrient content can be achieved with the use
      of quick tests. These tests can be used to indirectly measure the nutrient
      content in animal slurries immediately before manure is applied on agricultural
      fields. The objective of this study was to assess the reliability of hydrometers,
      electrical conductivity meter and pens, and Agros N meter against standard
      laboratory methods. Manure samples were collected from 34 dairy farms in the
      Mammoth Cave area in central Kentucky. Regression equations were developed for
      combined and individual counties located In the area (Barren, Hart and Monroe).
      Our results indicated that accuracy in nutrient estimation could be improved if
      separate linear regressions were developed for farms with similar facilities in a
      county. Direct hydrometer estimates of total nitrogen were among the most
      accurate when separate regression equations were developed for each county (R2 =
      0.61, 0.93, and 0.74 for Barren, Hart and Monroe county, respectively).
      Reasonably accurate estimates (R2 > 0.70) were also obtained for total nitrogen
      and total phosphorus using hydrometers, either by relating specific gravity to
      nutrient content or to total solids content. Estimation of ammoniacal nitrogen
      with Agros N meter and electrical conductivity meter/pens correlated well with
      standard laboratory determinations, especially while using the individual data
      sets from Hart County (R2 = 0.70 to 0.87). This study indicates that the use of
      quick test calibration equations developed for a small area or region where farms
      are similar in terms of manure handling and management, housing, and feed ration
      are more appropriate than using "universal" equations usually developed with
      combined data sets. Accuracy is expected to improve if individual farms develop
      their own calibration curves. Nevertheless, we suggest confidence intervals
      always be specified for nutrients estimated through quick testing for any
      specific region, county, or farm.

PMID- 15974266
TI  - Nickel adsorption on the modified pine tree materials.
AB  - Removal of nickel ions from aqueous solutions containing 1-100 mg l(-1), using
      pine tree (Pinus nigra) materials modified with HCl, was investigated on a
      laboratory scale. For this purpose, two natural adsorbents such as the modified
      pine bark (MPB) and the modified pine cone (MPC) materials with HCl solution were
      studied. At first, the required concentration level of the HCl solution for the
      modification was observed, and then this was followed by the determinations of
      optimum levels of adsorbent amount, stirring rate, contact time and pH values.
      Various adsorption isotherms were also obtained by using different concentrations
      of the heavy metal cations tested in the experiment. As a result, the maximum
      removal efficiency levels obtained were as follows; 97% for the modified pine
      bark at pH 8 and 80% for the modified pine cone at pH 8.

PMID- 15974267
TI  - A pilot scale evaluation for adsorptive removal of lead (II) using treated
      granular activated carbon.
AB  - Wastewaters discharged from the defence serviceable industries pose a serious
      environmental hazard due to their heavy metal load. The present study focused on
      optimizing the operational variables viz, hydraulic loading rate, bed height and
      feed concentration through bench scale study and using that for assessing the
      efficiency of pilot scale system with sulphur loaded carbon (AC-S) as the
      adsorbent in the removal of Pb (II). Static mode adsorption studies were also
      carried out for Pb (II) removal using treated (AC-S) and untreated carbon (AC).
      AC-S shows about 35 percent increase in maximum adsorption capacity over that on
      AC. The maximum adsorption capacity in the column mode for Pb (II) at the
      optimized conditions: bed height of 0.4 m, hydraulic loading rate of 7.5 m3h(
      1)m(-2) and the feed concentration of 6 mg l(-1) for achieving 50% breakthrough
      concentration was found to be 2.89 mg g(-1). Adsorption mechanism involved during
      Pb (1) in the column has also been explored. Bohart-Adams model was used for
      modeling the bench scale data and predicting the adsorption behavior at pilot
      scale level.

PMID- 15974268
TI  - Solar photocatalytic oxidation of pretreated wastewaters: laboratory scale
      generation of design data for technical-scale double-skin sheet reactors.
AB  - Batchwise heterogeneous photocatalytic oxidation of model wastewater (solutions
      of the azo dye "Acid Orange 7" in tap water) has been performed in a laboratory
      scale stirred vessel reactor with non-submerged UV-A lamps using titanium dioxide
      "P25" as photocatalyst. Comparison to results of solar pilot-scale Plexiglass
      double-skin sheet reactor (DSSR) experiments indicates that the lab-scale method
      may predict area demand for technical-scale DSSR design. Characteristic UV-A
      fluences leading to TOC or COD reduction to e(-1) of the initial concentrations
      were determined in lab-scale stirred vessel experiments for treated effluents of
      seven different industrial branches, secondary municipal effluent and
      biologically treated greywater. Predicted areas for solar photocatalytic
      oxidation of these effluents in DSSRs yielding mineralization of 95% of organics
      in 100 m3 of the respective effluents for a TiO2 concentration of 2 g l(-1) and a
      sky and solar radiation of 3.9kWh m(-2) d(-1) within one day greatly varied from
      below 6,000 m2 (biologically treated lubricating oil refinery effluent) to more
      than 100,000 m2 (highly saline biologically treated effluent of chemical
      industry). Especially municipal and refinery effluents (except oil reclaiming)
      have been identified as promising candidates for reuse after solar photocatalytic
      oxidation. Mineralization efficiency was decreasing with increasing alkalinity of
      effluents. This was interpreted by competition of hydrogen carbonate anions with
      organics for binding sites on photocatalyst surface and by OH radical scavenging
      by hydrogen carbonate. Dependence on alkalinity was superimposed by salinity
      influence as some effluents with high alkalinity also exhibited high salt
      concentrations (especially chloride).

PMID- 15974269
TI  - Comparison of the life-time of P25 and A11 TiO2 in a labyrinth flow photoreactor.
AB  - A series of experiments for the comparison of activity and life-time of anatase
      titanium dioxide, Tytanpol All (Chemical Factory "Police", Poland) with Degussa
      P25 (Germany) was conducted in a labyrinth flow reactor with an immobilized
      catalyst bed. Phenol, with relatively high concentration up to 100 mg dm(-3), was
      chosen as a model organic compound. Photocatalytic materials were characterized
      by determination of: phenol decomposition degree, reaction rate constant, band
      gap energy, FTIR spectra and phase composition. The pureanatase Tytanpol All
      shows comparable activity as Degussa P25. However, the life-time of P25 Degussa
      at high phenol concentration was lower compared to that of anatase A11 because of
      the carbon deposit formation on P25 surface. The catalytic activity of rutile
      phase in P25 in the reaction of carbon deposits formation is postulated.

PMID- 15974270
TI  - Laboratory and pilot-scale phosphate and ammonium removal by controlled struvite
      precipitation following coagulation and flocculation of swine wastewater.
AB  - To reduce the suspended solids load to a trickling filter installation, raw swine
      effluent was pre-treated with ferric chloride and a cationically charged
      polyacrylamide coagulant resulting in unexpected struvite accumulation downstream
      of this post-separation process. Using this pre-treated swine manure, struvite
      precipitation studies were carried out as a function of pH at laboratory and
      pilot batch and continuously operated scales. An optimal reaction time of 30 min
      was established for struvite precipitation in the pre-treated swine wastewater at
      pH 8.5, minimizing the co-precipitation of interfering minerals. Ferric chloride
      addition resulted in magnesium solubilization, such that no external additional
      source of magnesium was required for struvite formation. Aeration alone did not
      result in significant pH increases, so base addition was required for pH
      adjustment. X-ray diffraction revealed that the only crystalline phase produced
      was struvite. Removal of phosphate and ammonium attained 98% and 17% respectively
      in laboratory scale experiments. At the pilot-scale, removal attained 99% and 15%
      of phosphate and ammonium in both batch and continuously HRT = 1h) operated
      reactors.

PMID- 15974271
TI  - Color, dye and DOC removal, and acid generation during fenton oxidation of dyes.
AB  - The removal of color, dye and dissolved organic carbon by Fenton discoloration
      was investigated using the synthetic dye wastewaters containing various dyes
      (reactive blue 19, Eriochrome Black T or Fast Green FCF). The results indicated
      that discoloration of dyes was very rapid but mineralization of dyes was
      insignificant based on the removal of dissolved organic carbon. The rates of
      color, dye and dissolved organic carbon removal were in the order of reactive
      blue 19 > Fast Green FCF > Eriochrome Black T. The generation of SO(2-)4, and N(O
      )3, increased with the progress of the Fenton reaction. The concentrations of SO(
      2)4 and N(O-)3, generated are in the order of reactive blue 19 > Fast Green FCF>
      Eriochrome Black T. A mathematic model was proposed to formulate the formation of
      SO(2-)4 and N(O-)3 during dye degradation. Results indicated that one S
      containing and two N-containing functional groups are involved in the oxidation
      reaction, and that S-containing groups are involved in the oxidation reaction
      earlier than N-containing functional groups.

PMID- 15974272
TI  - Activated sludge is a potential source for production of biodegradable plastics
      from wastewater.
AB  - Increased utilization of synthetic plastics caused severe environmental pollution
      due to their non-biodegradable nature. In the search for environmentally friendly
      materials to substitute for conventional plastics, different biodegradable
      plastics have been developed by microbial fermentations. However, limitations of
      these materials still exist due to high cost. This study aims at minimization of
      cost for the production of biodegradable plastics P(3HB) and minimization of
      environmental pollution. The waste biological sludge generated at wastewater
      treatment plants is used for the production of P(3HB) and wastewater is used as
      carbon source. Activated sludge was induced by controlling the carbon: nitrogen
      ratio to accumulate storage polymer. Initially polymer accumulation was studied
      by using different carbon and nitrogen sources. Maximum accumulation of polymer
      was observed with carbon source acetic acid and diammonium hydrogen phosphate
      (DAHP) as nitrogen source. Further studies were carried out to optimize the
      carbon: nitrogen ratios using acetic acid and DAHP. A maximum of 65.84% (w/w)
      P(3HB) production was obtained at C/N ratio of 50 within 96 hours of incubation.

PMID- 15974273
TI  - Heap leaching of lead contaminated soil using biodegradable chelator [S,S]
      ethylenediamine disuccinate.
AB  - The feasibility of heap leaching Pb contaminated soil using biodegradable
      chelator [S,S]-ethylenediamine disuccinate ([S,S]-EDDS) in concentrations ranging
      from 10 to 40 mmol kg(-1) was assessed in a laboratory study. Treatment with 40
      mmol kg(-1) [S,S]-EDDS was the most efficient, removing 31.3% of soil Pb and
      producing a waste washing solution with a peak Pb concentration slightly
      exceeding 10 mM. The removal of Pb from simulated washing solution containing 10
      mM Pb by biodegradation of the Pb-[S,S]-EDDS complex and sorption of the released
      Pb on a vermiculite/soya meal/Slovakite based permeable bed was completed in 7.5
      days. Lead recovery from washing solutions with higher molarity was significantly
      slower. Lead fractionation and bioavailability were assessed 6-months after soil
      treatment. Heap leaching removed Pb proportionally from carbonates (approx. 25%
      Pb) and organic matter (> 50% Pb), the two main Pb-bearing soil fractions,and
      increased the small pool of Pb soluble in the soil solution. The latter had no
      effect on Pb phytoavailability. Accumulation of Pb in leaves of the reported
      hyperaccumulator species Thlaspi goesingense was < 20 mg kg(-1) in all
      treatments, comparable to the Pb concentration in lettuce (Latuca sativa). Soil
      treatment with 40 mmol kg(-1) [S,S]-EDDS reduced concentrations of Pb orally
      accessible in the stomach and intestine phase from initial 234.0 and 52.5 mg kg(
      1) to 157.8 and 29.7 mg kg(-1), respectively, according to Ruby's test. Our
      results indicate that heap leaching of Pb with [S,S]-EDDS is not a viable
      remediation option for the tested soil and conditions used.

PMID- 15974274
TI  - The utilization of sepiolite in landfill liners.
AB  - In this study, sepiolite and natural soil-added sepiolite mixtures were studied
      to find out whether they can be used as compacted landfill liner, as they are an
      economic alternative to the other compacted day liners or not. Geotechnical and
      physico-chemical properties of sepiolite and sepiolite mixtures, containing 25%
      and 50% natural soil by weight, and compacted at water contents ranging from 35%
      to 60%, were determined by hydraulic conductivity, leachate analysis, unconfined
      compression strength, consolidation, volumetric shrinkage and swelling tests. The
      test results showed that the compacted natural soil-added sepiolite mixtures
      exhibit lower permeability and swelling properties, and higher compressive
      strength than pure sepiolite. The overall evaluation of the results has revealed
      that the natural soil-added sepiolite showed good promise and it can be used as a
      landfill barrier due to its high capacity of contaminant adsorption.

PMID- 15974275
TI  - Biosorption of pentachlorophenol by fungal biomass from aqueous solutions: a
      factorial design analysis.
AB  - A 2(5-1) fractional factorial design was conducted for the biosorption of
      pentachlorophenol (PCP) using Aspergillus niger biomass. Effects of several
      factors on the percentage removal of PCP from aqueous solutions were evaluated.
      These factors were as follows: type of biomass (autoclaved- chemically modified);
      pH (3-11); concentration (1-10 mgl(-1)); temperature (6-32 degrees C); and
      dissolved oxygen (2.5-20 mgl(-1)). Time of shaking (equilibrium time), volume of
      the solution and mass of biomass were kept constant. The results showed that type
      of biomass and pH had a larger impact on the removal of PCP. Concentration of PCP
      in the aqueous solution, temperature, and dissolved oxygen only marginally
      affected the removal efficiency of PCP.

PMID- 15974276
TI  - Bioremediation of sediments from intensive aquaculture shrimp farms by using
      calcium peroxide as slow oxygen release agent.
AB  - A viable treatment procedure was developed in this research with calcium peroxide
      (CaO2) as a slow oxygen (O2) release agent for bioremediation of polluted
      sediments from intensive shrimp farms containing high organic carbon, nitrogen
      and phosphorus. Experiments with sediment treatment by CaO2 were carried out
      with, as well as without, biomass seeding at pH ranging from 6.5 to 8.5. The
      sediment treatment applying CaO2 without seeding yielded a BOD5, organic-C and
      organic-N removal up to 95%, 17.6% and 75%, respectively compared to the removal
      of 66%, 8.6% and 57%, respectively in the controlled treatment without CaO,
      addition. The investigations were also carried out with CaO2 dosage with biomass
      seeding at different food-to-microorganisms (F/M) ratio between 0.1 and 0.25. The
      BOD, organic-C and organic-N removal up to 92%, 17.6% and 73%, were achieved for
      a F/M ratio 0.1. The experimental results indicated complete organic-P removal
      within 5-7 days of treatment without seeding and within the initial 2 days of
      treatment with seeding. The present research revealed that, the application of
      CaO2 could enhance the degradation of organic-C, organic-N and organic-P during
      the treatment of polluted sediment.

PMID- 15974277
TI  - About the living will.

PMID- 15974278
TI  - Best practice for diabetes management.

PMID- 15974279
TI  - Making a difference.

PMID- 15974280
TI  - February issue. Mandatory retirement at age 65.

PMID- 15974281
TI  - More on PhD funding.

PMID- 15974282
TI  - The next chapter. Retirement planning should begin early in our careers.

PMID- 15974283
TI  - The next chapter. Retirement planning should begin early in our careers.

PMID- 15974284
TI  - No late bloomer.

PMID- 15974285
TI  - A positive or experience.

PMID- 15974286
TI  - Nurse appreciated.

PMID- 15974287
TI  - On nursing education.

PMID- 15974288
TI  - Fears for the future.

PMID- 15974289
TI  - An undergraduate research experience.

PMID- 15974290
TI  - Becoming an entrepreneur.

PMID- 15974291
TI  - Interprovincial partnership in nursing education.
AB  - The Canadian Nurses Association endorsed the position that baccalaureate
      education is essential to practise nursing. Provincial adoption of this position
      began efforts to increase seats in baccalaureate programs as early as the late
      1980s. These efforts have generated many different models of collaborative
      baccalaureate nursing programs in Canada. One model, the UNB-Humber Collaborative
      Nursing Program, began to offer nursing courses in the fall of 2001. As UNB
      already offered its basic baccalaureate program in four New Brunswick sites and
      Humber College had well-established nursing diploma and continuing education
      programs, a partnership approach to nursing education seemed beneficial to both
      institutions. This article describes, from the perspective of one faculty member
      in Ontario and one in New Brunswick, how the development and implementation of
      this collaborative program and its curriculum were guided by a similar
      philosophy. The authors describe how the curriculum values of primary health
      care, social justice and caring influenced their relationships in the program
      development process. They also discuss strategies the partnership has used for
      developing the curriculum collaboratively, ensuring similarity of courses across
      sites, addressing academic freedom and sharing and learning together.

PMID- 15974292
TI  - Sharing with the land of the dancing lights.
AB  - In this article, the authors discuss some of their experiences with an innovative
      project that involved a group of faculty engaged in a collegial model of
      mentorship through the use of distance technology. In 2001, Aurora College in
      Yellowknife, Northwest Territories, entered into contract with the Collaborative
      Nursing Program (CNP) in British Columbia to develop a four-year BSN program. The
      contract included a curriculum development and faculty mentoring package for each
      year of the new program. In preparation for implementing the first year of the
      new curriculum, a mentoring partnership was set up involving the Aurora faculty
      who would be teaching the first three faculty members from the CNP sites at North
      Island College in Courtenay, University College of the Cariboo in Kamloops and
      Selkirk College in Castlegar. Aside from the initial two-day face-to-face
      workshop in Yellowknife and the occasional meeting of individuals at nursing
      conferences, mentoring took place across the miles, via teleconferencing and e
      mail. At the end of the one-year project, all participants felt energized and
      enriched by the experience.

PMID- 15974293
TI  - Upholding the image of nursing.

PMID- 15974294
TI  - The Human Genome Project and advances in anthropological genetics.

PMID- 15974295
TI  - European ACP1*C allele has recessive deleterious effects on early life viability.
AB  - The acid phosphatase locus (ACP1) is a classical polymorphism that has been
      surveyed in hundreds of human populations worldwide. Among individuals of
      European ancestry, the ACP1*C allele occurs with an average frequency of
      approximately 0.05, whereas it is nearly absent in all other human populations.
      It has been hypothesized that this allele is maintained by overdominant selection
      among European populations. Here, we analyze ACP1 protein polymorphism data from
      more than 50,000 individuals previously surveyed in 67 populations across Europe
      as well as inheritance data from more than 6,000 European parent-offspring pairs
      to assess the signature of natural selection currently acting on this allele.
      Although we see a significant excess of ACP1*C heterozygotes relative to Hardy
      Weinberg expectations, we find no evidence that natural selection favors ACP1*C
      heterozygotes. Instead, ACP1*C appears to have a strongly deleterious and
      recessive fitness effect. We observed only 48.9% of expected homozygous offspring
      from heterozygous parents and significantly fewer homozygotes than expected
      within populations. Because parent-offspring pairs indicate a significant
      deficiency of ACP1*C homozygotes, we infer that viability selection is acting on
      ACP1*C homozygotes very early in life, perhaps before birth. We estimate that
      approximately 1.2% of all couples of European ancestry are composed of
      individuals who both carry the APC1*C allele. As such, selection against ACP1*C
      homozygotes may represent a nonnegligible contribution to the overall number of
      spontaneous abortions among women of European ancestry and may cause substantial
      fertility reductions among some combinations of parental genotypes.

PMID- 15974296
TI  - Seasonal variation of genotype-specific fertility and adaptation to endemic
      diseases: a study in past malarial areas of Italy.
AB  - Cyclic seasonal variation of genotype-specific fertility could interact with
      endemic diseases characterized by seasonal variation of severity resulting in
      changes of gene frequencies in the course of generations. Assuming that a given
      allele A has a frequency pw in infants conceived in the cold season and a
      frequency of ps in those conceived in the warm season and assuming that general
      fertility is the same in the two seasonal periods, the gene frequency in the
      population is pm = (pw + ps)/2; this frequency remains constant over the course
      of generations. The introduction of an endemic disease bearing negatively on
      general fertility and characterized by a seasonal pattern of severity could
      result in variations of the A allele frequency. If the maximum of endemicity
      coincides with the maximum value of the allele A frequency, the frequency of
      allele A will progressively decrease. A simple mathematical algorithm has been
      applied to two polymorphic enzymes (ACP1 and G6PD) correlated with past malarial
      morbidity in Sardinia and the Po River delta. The two systems show differences in
      gene frequency in relation to season of conception. The theoretical changes fit
      quite well with the data observed in Sardinian and Po delta populations, thus
      suggesting a mechanism that is an alternative to or concurrent with the classical
      mechanism that assumes a direct connection between the genetic systems and the
      biology of the malarial parasite.

PMID- 15974297
TI  - Fine mapping and SNP analysis of positional candidates at the preeclampsia
      susceptibility locus (PREG1) on chromosome 2.
AB  - Genome scans in Icelandic, Australian and New Zealand, and Finnish families have
      localized putative susceptibility loci for preeclampsia/ eclampsia to chromosome
      2. The locus mapped in the Australian and New Zealand study (designated PREG1)
      was thought to be the same locus as that identified in the Icelandic study. In
      both these studies, two distinct quantitative trait locus (QTL) regions were
      evident on chromosome 2. Here, we describe our fine mapping of the PREG1 locus
      and a genetic analysis of two positional candidate genes. Twenty-five additional
      microsatellite markers were genotyped within the 74-cM linkage region defined by
      the combined Icelandic and Australian and New Zealand genome scans. The overall
      position and shape of the localization evidence obtained using nonparametric
      multipoint analysis did not change from that seen previously in our 10-cM
      resolution genome scan; two peaks were displayed, one on chromosome 2p at marker
      D2S388 (107.46 cM) and the other on chromosome 2q at 151.5 cM at marker D2S2313.
      Using the robust two-point linkage analysis implemented in the Analyze program,
      all 25 markers gave positive LOD scores with significant evidence of linkage
      being seen at marker D2S2313 (151.5 cM), achieving a LOD score of 3.37 under a
      strict diagnostic model. Suggestive evidence of linkage was seen at marker D2S388
      (107.46 cM) with a LOD score of 2.22 under the general diagnostic model. Two
      candidate genes beneath the peak on chromosome 2p were selected for further
      analysis using public single nucleotide polymorphisms (SNPs) within these genes.
      Maximum LOD scores were obtained for an SNP in TACR1 (LOD = 3.5) and for an SNP
      in TCF7L1 (LOD = 3.33), both achieving genome-wide significance. However, no
      evidence of association was seen with any of the markers tested. These data
      strongly support the presence of a susceptibility gene on chromosome 2p11-12 and
      substantiate the possibility of a second locus on chromosome 2q23.

PMID- 15974298
TI  - Gene by smoking interaction: evidence for effects on low-density lipoprotein size
      and plasma levels of triglyceride and high-density lipoprotein cholesterol.
AB  - We seek to determine whether significant gene x smoking interaction effects exist
      on plasma triglyceride (TG) levels, HDL cholesterol (HDL-C) level, and median LDL
      particle diameter (LDL-MPD) in Mexican American families enrolled in the San
      Antonio Family Heart Study. The sample consisted of 1,392 individuals distributed
      in 42 extended pedigrees, ranging in age from 16 years to 92 years. Separate
      quantitative genetic analyses were carried out for TG and HDL-C level and LDL-MPD
      using a maximum-likelihood-based variance decomposition approach while
      simultaneously adjusting for age and sex. Initial heritability estimates
      demonstrated significant (p < 0.001) additive genetic contributions to all three
      traits (h2 range 0.50 - 0.54). To test for a gene x smoking interaction, we
      included in the model additional smoking-status-specific variance terms and a
      genetic correlation term between smokers and nonsmokers. Comparisons of nested
      models revealed significant evidence (p < 0.01) for a gene X smoking interaction
      effect on TG level and LDL-MPD and possible evidence for an effect on HDL-C
      level. These results indicate that the gene or suite of genes regulating each of
      these phenotypes is likely the same in smokers and non-smokers but that smoking
      may alter the expression of genes, particularly those influencing TG level and
      LDL-MPD.

PMID- 15974299
TI  - Differentiation of mitochondrial DNA and Y chromosomes in Russian populations.
AB  - The genetic composition of the Russian population was investigated by analyzing
      both mitochondrial DNA (mtDNA) and Y-chromosome loci polymorphisms that allow for
      the different components of a population gene pool to be studied, depending on
      the mode of DNA marker inheritance. mtDNA sequence variation was examined by
      using hypervariable segment I (HVSI) sequencing and restriction analysis of the
      haplogroup-specific sites in 325 individuals representing 5 Russian populations
      from the European part of Russia. The Y-chromosome variation was investigated in
      338 individuals from 8 Russian populations (including 5 populations analyzed for
      mtDNA variation) using 12 binary markers. For both uniparental systems most of
      the observed haplogroups fell into major West Eurasian haplogroups (97.9% and
      99.7% for mtDNA and Y-chromosome haplogroups, respectively). Multidimensional
      scaling analysis based on pairwise F(ST) values between mtDNA HVSI sequences in
      Russians compared to other European populations revealed a considerable
      heterogeneity of Russian populations; populations from the southern and western
      parts of Russia are separated from eastern and northern populations. Meanwhile,
      the multidimensional scaling analysis based on Y-chromosome haplogroup F(ST)
      values demonstrates that the Russian gene pool is close to central-eastern
      European populations, with a much higher similarity to the Baltic and Finno-Ugric
      male pools from northern European Russia. This discrepancy in the depth of
      penetration of mtDNA and Y-chromosome lineages characteristic for the most
      southwestern Russian populations into the east and north of eastern Europe
      appears to indicate that Russian colonization of the northeastern territories
      might have been accomplished mainly by males rather than by females.

PMID- 15974300
TI  - Sicilian provinces: population subdivisions revealed by surname frequencies.
AB  - The Sicilian population has a complex history of colonization and invasions that
      have influenced the genetic composition of the nine provinces of the island.
      Because surnames are patrilineally inherited, they simulate a Y-chromosome
      nonrecombinant genetic locus. We used surname data and a specific sampling
      strategy to describe the major subdivisions in each province and for the whole
      island of Sicily. The high number of families per surname in two provinces can be
      related to inbreeding as a result of founder events. Each province shows a major
      division, which, according to local historical events, likely represents cultural
      and probably genetic differences between east and west, between north and south,
      or between the inner regions and the coastal area. On the island level surnames
      reproduce the same separation, obtained by others with genes, of the eastern area
      from the western area. The separation is attributed to Greek influence in the
      east and to Phoenician-Carthaginian-Norman influence in the west. This separation
      crosses the two central provinces of Agrigento and Caltanissetta.

PMID- 15974301
TI  - LOC 390443 (RNase 9) on chromosome 14q11.2 is related to the RNase A superfamily
      and contains a unique amino-terminal preproteinlike sequence.
AB  - A new member of the human RNase A superfamily is reported. Identified in the
      human genome assembly as LOC 390443, this locus is located 128 kb telomeric to
      the established RNase A gene family cluster on chromosome 14q11.2. The amino acid
      sequence of this locus is sufficiently similar to the eight previously identified
      gene family members to warrant a designation as RNase 9. RNase 9 is expressed in
      a wide range of human tissues. In addition, a 30-amino acid sequence lying
      between a 26-amino acid putative signal peptide and the last 148 amino acids that
      align with the other RNases A is not seen in other members of the RNase A
      superfamily in any species. Nucleotide and amino acid sequences of RNase 9 in 13
      nonhuman primate species were determined and indicate several conserved sites
      but, also, an excess of nonsynonymous substitutions, about one-third of which are
      radical substitutions. This suggests that RNase 9, similar to several other human
      RNases A, has been under diversifying selection in the primates. Data from the
      mouse and rat genomes indicate that RNase 9 is also present in rodents, thus
      making it older than most of the established members of the human RNase A
      superfamily. Many of the human RNases A have been shown to have antimicrobial,
      antiviral, or antiparasitic functions involved in host-defense mechanisms. The
      features of RNase 9 described here suggest that it, too, may be involved in host
      defense and that it, along with the rest of the superfamily, may prove to have
      played an important role in anthropoid evolution.

PMID- 15974302
TI  - Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in a Brazilian
      mixed population.
AB  - The GSTM1 and GSTT1 null genotype frequencies were significantly different
      between 658 nonblack and black healthy blood donors from a Brazilian mixed
      population (Rio de Janeiro). The GSTM1 phenotype distribution was not in Hardy
      Weinberg equilibrium in either group, mainly because of an excess of the
      GSTM1*A/*B genotype.

PMID- 15974303
TI  - Allele frequencies of D21S11, FGA, TH01, and VWA in populations of the Balkans.
AB  - This study is part of an extensive investigation of the genetic relationship
      between Balkan populations, especially the Aromuns. Allele frequencies of four
      STRs (D21S11, FGA, TH01, VWA) from Macedonians (Skopje), Gramostian Aromuns from
      the Stip region (Macedonia), Moskopolian Aromuns from Krusevo (Macedonia), and
      Musequiar Aromuns from Dukasi (Albania) are presented.

PMID- 15974304
TI  - Stopping the epidemic: what more can you do?

PMID- 15974305
TI  - Wrist band ID board: a simple training tool for assisting in dealing with "found
      down" patients.

PMID- 15974306
TI  - A recorded refusal: EMS telemedicine system previewed.

PMID- 15974307
TI  - Public service fire and EMS. Bright sun and a robust present in Berkely County,
      WV.

PMID- 15974308
TI  - Rush to judgment: wasting time, trust and people.

PMID- 15974309
TI  - Beware of the podium pirates.

PMID- 15974310
TI  - T-bone: you'll never please 'em all.

PMID- 15974311
TI  - Work injury.

PMID- 15974312
TI  - An interview with O.J. Doyle on EMS and the political process. Interview by
      Raphael M. Barishansky.

PMID- 15974313
TI  - The new Salvation Army. How the U.S. military is keeping soldiers alive, and what
      it means for EMS.

PMID- 15974314
TI  - Communicating the right messages during difficult times. How eight weeks defined
      an organization.

PMID- 15974315
TI  - Emergency stabilization of unstable pelvic fractures.
AB  - Pelvic ring fractures resulting from high-energy and/or mass mechanisms can cause
      life-threatening severe bleeding, however, devices can be applied by EMS at the
      emergency scene to help slow or reduce that possibility. Circumferential
      compression is an effective and safe method to stabilize open book pelvic
      fractures.

PMID- 15974316
TI  - Helmet removal in athletics: the "big debate".
AB  - C-spine management in athletics by EMS is an ongoing topic of discussion. While
      there is obviously more than one method to achieve the end goal, a few techniques
      are no longer recommended. Probably the biggest change, as discussed here, is
      that the helmet really does not need to be removed for transport. However, as
      recommended by the Interagency Task Force, the facemask should be removed if the
      athlete needs to be transported. In this case, regardless of the tool used to do
      it, the facemask must be removed completely and quickly, without causing any
      additional undue movement of the patient's head. Ensure that all of the retaining
      clips on the facemask are cut completely to allow easier access to the injured
      athlete.

PMID- 15974317
TI  - Autonomic dysreflexia in spinal cord injury.

PMID- 15974318
TI  - CAAS: the view from the inside.

PMID- 15974319
TI  - His and hers abdominal pain.
AB  - Abdominal pain should not be dismissed without proper evaluation. A patient
      presenting with acute, severe abdominal pain is best transported to the emergency
      room for treatment. While gender issues remain a delicate subject, proper
      prehospital care prevents patient deterioration, tissue loss and loss of life.
      Prehospital information is invaluable. Due to unforeseen complications, including
      patient deterioration, the history you obtain on scene may be the only
      information available to the medical team at the hospital. Professional care
      begins in the prehospital setting. Knowledge, skill and experience will guide
      you.

PMID- 15974320
TI  - True medical emergencies.

PMID- 15974321
TI  - Crash course. Why sugar and caffeine are not the answer to the stress of your
      crazy schedule.

PMID- 15974322
TI  - Workout program for a posted ambulance.

PMID- 15974323
TI  - Got GERD?

PMID- 15974324
TI  - Genital cutting and western discourses on sexuality.
AB  - This article explores dominant discourses surrounding male and female genital
      cutting. Over a similar period of time, these genital operations have separately
      been subjected to scrutiny and criticism. However, although critiques of female
      circumcision have been widely taken up, general public opinion toward male
      circumcision remains indifferent. This difference cannot merely be explained by
      the natural attributes and effects of these practices. Rather, attitudes toward
      genital cutting reflect historically and culturally specific understandings of
      the human body. In particular, I suggest that certain problematic understandings
      of male and female sexuality are deeply implicated in the dominant Western
      discourses on genital surgery.

PMID- 15974325
TI  - Street smarts and urban myths: women, sex work, and the role of storytelling in
      risk reduction and rationalization.
AB  - Storytelling has a strong tradition in inner-city American communities. In this
      article, we examine patterns of storytelling among a sample of drug-using women
      from New York City who engage in street-based sex work. We consider two
      particular formats of storytelling for analysis: "street smarts" and "urban
      myths." Street smarts are stories of survival, and urban myths are compilations
      of street legends spread by word of mouth. The narratives are filled with tales
      of extreme risk across situations. The women used the stories to delineate the
      boundaries of risk as well as to rationalize risks they deemed to be inevitable
      but temporary in their lives. Few of the women capitalized on the greater
      instructive quality of the stories toward increased risk reduction, which may
      relate to the women's distance from an identity of "sex worker." If properly
      harnessed, the strength of storytelling suggests new avenues for risk-reduction
      interventions.

PMID- 15974326
TI  - Situating stress: lessons from lay discourses on diabetes.
AB  - In response to the serious toll diabetes takes on health and resources,
      researchers increasingly are examining physical and psychological pathways that
      affect and are affected by diabetes, including stress. Although biomedical
      researchers and practitioners are beginning to recognize the association between
      stress and diabetes onset and management, laypersons have long-standing and
      extensive insights into the multiple ways in which stress is associated with the
      diabetes disease process. In this article, we examine lay perspectives on stress
      and diabetes among a multiethnic sample of 80 adults. Participants suggest
      varying arenas in which stress intersects with diabetes, including stress as
      implicated in the origin of diabetes, as a threat to maintaining glycemic
      control, as a challenge to self-management, and as a precursor to and a
      consequence of diabetes complications. An improved understanding of such
      perspectives may enhance appropriate disease management and develop a more valid
      conceptualization of stress in research efforts.

PMID- 15974327
TI  - Claiming respectable American motherhood: homebirth mothers, medical officials,
      and the state.
AB  - Based on ethnographic research regarding public policy and grassroots organizing
      for midwifery in Virginia, this article explores how medical discourses around
      appropriate health care practices intersect with state discourses about what
      practices are considered "respectable" versus "pathological" for its citizens. In
      recent legislative debates about the legalization of direct-entry midwifery,
      medical officials have extended their criticism of midwifery and homebirth to
      mothers who resist state-sanctioned childbirth practices. This article examines
      how medical officials challenge the respectable mothering practices of
      homebirthers by linking them with women they deem pathological--child abusers,
      negligent mothers, and drug users--and placing them outside the cadre of "normal"
      American mothers who acknowledge the "logical" and "natural" superiority of
      biomedical childbirth practices. I also address homebirth mothers' responses,
      which assert that their political advocacy for midwives is a respectable
      mothering practice because they are responsible citizens who desire what they
      deem the best care for their children.

PMID- 15974328
TI  - Self-mortification and the stigma of leprosy in northern India.
AB  - This article examines the biocultural dynamics of social discrimination and
      physical disfigurement among people with leprosy, or Hansen's disease (HD), in
      Banaras, northern India. Based on the narratives and observations ofpeople living
      in colony and street settings, I trace three destructive processes by which the
      social stigmata of leprosy become physically expressed. First, strategies of
      concealment further the progression and spread of HD through late detection and
      undertreatment. Second, the internalization of stigma can lead to bodily
      dissociation and injury through self-neglect. Finally, some people intentionally
      seek injuries under conditions of desperate poverty. As a result of such
      mortification processes, these people came to embody, quite literally, the
      prejudices that exacerbated their condition in the first place.

PMID- 15974329
TI  - Interview with Ronald G. Spaeth, FACHE, president, Evanston Northwestern
      Healthcare Foundation, Northbrook, Illinois. Interview by Kyle Grazier.

PMID- 15974330
TI  - The link between a formal debt policy and replacement reserves.

PMID- 15974331
TI  - Proxemics in clinical and administrative settings.

PMID- 15974332
TI  - What do we owe the dying? Strategies to strengthen end-of-life care.
AB  - More than 2.5 million Americans died last year, and a majority of these persons
      died within an inpatient hospital setting. The demand for inpatient hospital care
      at the end of life (EOL) will increase appreciably as the population continues to
      age; several leading bodies, including the Institute of Medicine, have called for
      an expansion of evidence-based, patient-centered EOL care. In an attempt to
      assist healthcare executives to meet the needs of the increasing number of dying
      patients, we reviewed four hospital-based, best-practice EOL programs. Following
      this review, we defined an operational planning process that yields three ways to
      improve EOL care programs. The improvement of EOL care programs should constitute
      a great benefit to those organizations concerned with improving the quality of
      patient care, reducing the costs associated with the treatment of dying patients,
      and responding to the standards of national credentialing bodies.

PMID- 15974333
TI  - The revolution in hospital management.
AB  - Five healthcare systems that have either won the Malcolm Baldrige National
      Quality Award in Health Care or been documented in extensive case studies share a
      common model of management: they all emphasize a broadly accepted mission;
      measured performance; continuous quality improvement; and responsiveness to the
      needs of patients, physicians, employees, and community stakeholders. This
      approach produces results that are substantially and uniformly better than
      average, across a wide variety of acute care settings. As customers, courts, and
      accrediting and payment agencies recognize this management approach, we argue
      that it will become the standard for all hospitals to achieve. This article
      examines documented cases of excellent hospitals, using the reports of three
      winners of the Baldrige National Quality Award in Health Care and published
      studies of other institutions with exceptional records.

PMID- 15974334
TI  - The financial performance of integrated health organizations.
AB  - This study examines the impact of integration strategies on the financial
      performance of hospitals, physicians, and health plans over time. Results from a
      study of 36 large integrated health organizations (IHOs) suggest that financial
      performance is adversely affected by the scale of investment in integration but
      not necessarily by the timing or sequencing of the investments made. The results
      also suggest that some integration strategies have more detrimental effects on
      financial performance than do others. Finally, the results show that centralized
      integrative structures appear more financially successful than are less
      centralized structures.

PMID- 15974335
TI  - Short-term effect of physical exercise at lactate threshold on choice reaction
      time.
AB  - The duration of the enhancement of choice reaction task efficiency by physical
      exercise at lactate threshold was studied. After healthy male students completed
      the exercise or nonexercise (control) period for 10 min., they performed a three
      choice reaction task for 20 min. The mean heart rate during the choice reaction
      task after the exercise was higher than that after the control period (p < .05).
      For average percentage of correct answers, there were no significant differences
      between the exercise and control conditions. The reaction time during the first 8
      min. of the 20-min. choice reaction task after the exercise period was less than
      that after the control period and increased gradually thereafter. In conclusion,
      whereas the choice reaction time was improved by physical exercise at around
      lactate threshold, the positive effects were seen mainly in the early stages of
      the task.

PMID- 15974336
TI  - Oriental approaches to masculine and feminine subtle energy principles.
AB  - According to ancient Indian and Chinese texts the subtle energy (prana or chi)
      flows through several thousand anatomically indistinguishable channels or
      meridians (nadis). Three channels are especially important (ida, pingala, and
      sushumna). The ida and pingala channels correlate with left and right uninostril
      breathing, respectively. Like yin and yang, they are considered to represent the
      masculine and feminine principles present in all creation irrespective of sex.
      From this perspective these principles are assumed to be present simultaneously
      in persons of both sexes. This suggests that any sex-specific effects of
      uninostril breathing may be associated with sex-based physiological differences,
      not with 'masculine' and 'feminine' attributes of the channels (and the
      corresponding nostrils).

PMID- 15974337
TI  - Ratings of speech naturalness of children ages 8-16 years.
AB  - The focus of this cross-sectional study was the investigation of Speech
      Naturalness (speech that sounds normal or natural to the listener) of 60 normal
      speaking children and adolescents between the ages of 8 and 16 years. 26 naive
      adult listeners rated the naturalness of videotaped and computer-presented speech
      samples, using a 9-point-Likert rating scale (1: highly natural sounding speech
      and 9: highly unnatural sounding speech). The children and adolescents who
      participated as speakers were distributed among 5 age groups (8, 10, 12, 14, and
      16 yr.) with 6 boys and 6 girls in each group. Each child demonstrated normal
      articulation, language, voice, and speech fluency skills. Age and sex comparisons
      indicated boys' and girls' speech was rated comparably; however, 8-yr.-olds'
      speech was rated as significantly less natural than those of 12-, 14-, and 16-yr.
      olds. Preliminary ratings of Speech Naturalness for normal speaking children were
      presented. Suggestions for the clinical application of the findings as a target
      criterion in treatment programs with communicatively impaired children were
      suggested. Replication with a larger and more representative sample is in order.

PMID- 15974338
TI  - Effects of display characteristics and individual differences on preferences of
      VDT icon design.
AB  - This study explored the effects of display characteristics such as
      target/background color combination, single/simultaneous presentation, and
      individual differences by sex, and design specialty on preferences of VDT icon
      design. The results indicated black targets (black-on-white, black-on-yellow) and
      black backgrounds (red-on-black, yellow-on-black) were the most popular and white
      targets (white-on-red, white-on-black) and white backgrounds (blue-on-white, red
      on-white) were the second most popular. As for the chromatic color combinations,
      yellow-on-blue was the most favored. Subjects rated color combinations under
      single presentation higher than those under simultaneous presentation. Women
      rated purplish targets and rated purplish and blue backgrounds higher than men.
      Subjects with design background favored black more either as a target or
      background, but they favored turquoise less than those without design background.

PMID- 15974339
TI  - From randomness to stability.
AB  - The present study describes how the association between randomly chosen variables
      changes at the successive steps of temporal processes to converge into stable
      values as suggested by I. Prigogine. To generalize the results to any specific
      area so results may be applied to concrete problems in different sciences,
      randomly chosen matrices of random numbers were successively multiplied to
      generate temporal sequences that before reaching stability had different number
      of steps. Our results indicate that the obtained poliphasic stability is
      irreversible.

PMID- 15974340
TI  - Arthritic pain, aging, and psychomotor decline in people with HIV.
AB  - Arthritic pain and subsequent immobility are common in people with Human
      Immunodeficiency Virus (HIV) and in persons of older ages. It is hypothesized
      that such pain may contribute to psychomotor impairment commonly observed with
      HIV and aging. Empirical evaluation of this hypothesis among older persons with
      HIV and consideration of treatment should be undertaken.

PMID- 15974341
TI  - Motion as input: a functional explanation of movement effects on cognitive
      processes.
AB  - Motion is often thought of as the result of perceptual and higher cognitive
      processes. Although this idea has been investigated in myriad ways, the
      understanding of how movements tune cognitive processes is still in its infancy.
      The present study examined the nonaffective tuning of movements (arm extension
      and arm flexion) on heuristic and systematic processes. In a departure from
      recent cognitive tuning models, a model was derived that defines the tuning
      effect based on the movement goal and not on the movement position. In the
      experiment, participants moved toward an extension or flexion position with a
      movement goal which connected the movement with either an avoidance or an
      approach function. Analysis indicated that cognitive tuning is a product of the
      movement goal rather than the movement position. Implications for models of motor
      control as well as for cognitive tuning models are presented.

PMID- 15974342
TI  - Relationship of perceived physical self-concept and physical activity level and
      sex among young children.
AB  - The aim of this study was to investigate the relationship between level of
      physical activity and perceived physical self-concept of young children. The
      sample comprised 364 children from Slovenia, aged 6.4 yr. (SD = 0.3), of which
      179 were boys and 185 girls. Parents and teachers reported children's physical
      activity using the Harro questionnaire. We divided children into Low and High
      Activity groups based on their mean scores. The children completed Stein's
      Children's Physical Self-concept Scale, which assesses Global Physical Self
      concept and the subdomains of Physical Performance, Physical Appearance, and
      Weight Control behavior. Two-way analysis of variance with both sex and physical
      activity levels, and their interaction were used to examine differences in
      Physical Self-concept. There were significant differences between the Low and
      High Activity groups on scores for global Physical Self-concept Scale, Physical
      Performance, and Weight Control, on which children from the High Activity group
      scored higher; whereas on the subscale Physical Appearance, there were no
      significant differences. There were no significant sex differences on the
      Physical Self-concept Scale. The most important conclusion of this research
      indicates the theoretical assumptions that Physical Activity and perceived
      Physical Self-concept are related. Direction of the relationship remains
      unclarified.

PMID- 15974343
TI  - Effect of perceiving computing to be an acquirable skill upon a computer-mediated
      serial recall task.
AB  - Serial recall tasks assess the capacity of verbal short-term memory. The
      perception of computing as an acquirable skill rather than a fixed ability
      affected performance upon computer-based serial recall tasks but did not affect
      performance on comparable pencil-and-paper tasks. Computerized versions of
      traditional assessments should control for this.

PMID- 15974344
TI  - A pilot study comparing physiological responses of phase III cardiac patients to
      recumbent and upright exercise using the RPE scale.
AB  - Ratings of perceived exertion (RPE) are used for exercise programming of cardiac
      rehabilitation patients, whenever it is difficult to use heart rate to set
      intensity due to medication or other factors. This investigation examined the
      physiological responses to two stepping exercise modes (upright and recumbent) at
      the same RPE. Analysis indicated significant physiological differences between
      the modes of exercise which may be mediated by postural differences.
      Specifically, the physiological responses to the recumbent exercise, but not the
      upright exercise, had the expected relationship with RPE, with recumbent stepping
      requiring less physiological effort than the upright stepping at the same RPE. As
      such, we cannot recommend with confidence that the prescription for upright
      exercise be made based on data from recumbent exercise or vice-versa.

PMID- 15974345
TI  - Factors in athletic achievement: reply to Van Rossum (2004).
AB  - Several lines of evidence have questioned the contribution of innate talents to
      achievement. Nonetheless, it is also apparent that belief in talent is still
      common and affects perceptions that athletes form about themselves and fellow
      competitors about different levels of achievement.

PMID- 15974346
TI  - Novel stimuli are negative stimuli: evidence that negative affect is reduced in
      the mere exposure effect.
AB  - Repeated exposure of a nonreinforced stimulus results in an increased preference
      for that stimulus, the mere exposure effect. The present study repeatedly
      presented positive, negative, and neutrally affective faces to 48 participants
      while they made judgments about the emotional expression. Participants then rated
      the likeability of novel neutrally expressive faces and some of these previously
      presented faces, this time in their neutral expression. Faces originally
      presented as happy were rated as the most likeable, followed by faces originally
      presented as neutral. Negative and novel faces were not rated significantly
      differently from each other. These findings support the notion that the increase
      in preference towards repeatedly presented stimuli is the result of the reduction
      in negative affect, consistent with the modified two-factor uncertainty-reduction
      model and classical conditioning model of the mere exposure effect.

PMID- 15974347
TI  - Effects of choice on performance in two cultures.
AB  - Research in Japan and the United States has demonstrated that learning and memory
      may be improved when individuals are permitted to choose materials to be learned.
      In Japanese studies, the effects appear to be limited to the specific materials
      actually chosen, whereas in the United States, choice enhances recall of chosen
      as well as other materials that are later assigned. In the United States,
      personal choice has been hypothesized to affect both the learner's relationship
      to the chosen materials as well as motivation; in Japan personal choice affects
      the relationship between the learner and the chosen materials. Apparently the
      consequences of choice may vary in these cultures.

PMID- 15974348
TI  - Attention and reading skills.
AB  - Attention plays a critical role in information processing. Its adequate
      functioning is required for correct development of complex cognitive abilities
      and regular scholastic progress. Children with attention deficits often have
      difficulties in reading, writing, and arithmetic. The present study investigated
      interactions among reading skills, overall scholastic performance as rated by
      teachers, and components of attention: visual reaction time, simple immediate
      span of attention, and selectivity. The sample was 98 students in the first and
      second years of public junior high school (age range 11-14 years, M = 12.6, SD =
      1.2), i.e., with expected already well-established reading. Reading was evaluated
      using Comprehension, Accuracy, and Speed tests. Overall scholastic performance
      was obtained by means of teachers' ratings. Simple Reaction Time, Digit Span, and
      Color-Word Interference, included in a multitask computerized test, assessed
      attention. Analysis confirmed the hypothesis that the reading skills are strongly
      predictive of the Scholastic Assessment rated by the teachers. High scholastic
      ratings were correlated with Reading Speed and Accuracy rather than Reading
      Comprehension. Poor readers showed worse performances on the Digit Span test
      which measures simple immediate span of attention. Good and poor readers obtained
      a similar score on the Color-Word Interference task. This observation seems to
      contrast with the more common interpretation of this effect, suggesting that
      reading is an automatic process and, therefore, the semantic dimension overcomes
      the controlled perceptual one. According to other studies, an alternative
      explanation is suggested. In conclusion, present results confirm the hypothesis
      of a strong link among reading speed and accuracy, scholastic assessment as rated
      by teachers, simple immediate span of attention, and visual reaction time.

PMID- 15974349
TI  - Effect of reading with reversed speech on frequency of stuttering in adults.
AB  - This study explored the effect of reading with reversed speech on the frequency
      of stuttering. Eight adults who stutter served as participants and read four 300
      syllable passages while listening to three types of speech stimuli: normal speech
      (choral reading), reversed speech at normal speed, reversed speech at half speed,
      and a control condition of no auditory feedback. A repeated-measures analysis of
      variance showed a significant decrease in stuttering frequency in the choral
      reading condition but not in reversed speech at normal and half speed. However,
      the reversed speech at half-speed condition showed a large effect size (omega2 =
      0.32). Data suggest that a forward moving speech feedback is not essential to
      decrease the frequency of stuttering in adults who stutter.

PMID- 15974350
TI  - Changes in pulmonary function response to a 10-week controlled exercise program
      in sedentary elderly adults.
AB  - This randomized clinical trial was aimed to assess whether pulmonary function
      would change in sedentary elderly people after a controlled exercise program. 45
      participants over 75 yr. of age (M age 83.7 +/- 3.0) were assigned randomly to a
      control and two aerobic exercise groups of moderate and high intensity. In 10 wk.
      the program sessions were 40 min. in duration 3 days per week. Forced vital
      capacity (FVC) and forced expiratory volume in 1 sec. (FEV1.0) were measured pre-
      and post-intervention. After the training, the Moderate intensity group
      experienced significant mean change in FVC. In the High intensity group,
      significant changes were observed in both FVC and FEV1.0, but no change was noted
      for the Control group. The 10-wk. aerobic training of moderate or high intensity
      showed positive effects on pulmonary function in these elderly individuals. These
      exercise-induced changes may be dose-related.

PMID- 15974351
TI  - Effects of script types of Japanese loan words on priming performance.
AB  - 23 female undergraduate students (M=20 yr., 10 mo., SD=15 mo.) were given a word
      fragment completion task, containing a study and nonstudy list. In the present
      study, the effect of orthographic familiarity (e.g., script type) of a test item
      on a word-fragment completion task was examined. The script types of word stimuli
      (Katakana and Hiragana) were manipulated between a study and test phase. Priming
      effect was greater when the script type was the same between a study and test
      phase than in the cross-script condition. Further, even if the script type of
      word stimulus was different between study and test phases, a significant priming
      effect was obtained when the test fragment was orthographically familiar. These
      results suggested that not only the consistency of the perceptual feature of the
      stimulus word between study and test phases, but also orthographic familiarity of
      the stimulus word in the test phase facilitated priming effect in a word-fragment
      completion test.

PMID- 15974352
TI  - Effects of self-evaluation on the P300 event-related potential.
AB  - The effects of self evaluation on the P300 event-related potential (ERP) were
      explored with 56 participants (16 men, 40 women; M age = 23.4 yr., SD = 1.2)
      across three conditions. The conditions included (1) a standard ERP auditory
      oddball discrimination between a random target (15% occurrence) and standard
      stimuli (85% occurrence), (2) the oddball task followed by the additional
      cognitive task of maintaining a mental count of the target tones, and (3) the
      oddball task followed by the additional cognitive task of self-evaluating whether
      they felt surprised by the current occurrence of the target tone. The added
      cognitive requirements for Conditions 2 and 3 required the subjects to maintain a
      cognitive readiness for the secondary stimulus-related task during their sensory
      discrimination response for the standard oddball task. During the self-evaluation
      condition, the P300 amplitude was significantly larger across all recording
      locations than the regular oddball condition and the cognitive count condition.

PMID- 15974353
TI  - Choral reading with filtered speech: effect on stuttering.
AB  - This study investigated use of choral reading with filtered components of speech
      and whispered speech on the frequency of stuttering. Three passages read by a
      normal adult male were lowpass filtered with kneepoint frequencies at 100 Hz
      (approximate glottal source), 500 Hz (source and first formant), and 1 kHz
      (source and the first two formants). Along with a whispered passage, a normal
      passage, and a control condition, these stimuli were used in a repeated-measures
      design with 12 adult stutterers as they read passages while listening to one of
      the stimuli. Frequencies of stuttering in each condition were analyzed. The
      choral speech, the 500-Hz, the 1-kHz, and the whispered speech conditions all
      decreased the frequency of stuttering while the 100-Hz stimuli did not. It is
      suggested that articulatory events, chiefly the encoded speech output from the
      vocal tract, create effective cues and may induce fluent speech in people who
      stutter.

PMID- 15974354
TI  - Perception of large change in distribution of heel pressure during backward
      leaning.
AB  - We investigated the perception of the large change in distribution of heel
      pressure during backward leaning. Subjects were 12 healthy adults who reported
      perceiving a large change in distribution of heel pressure by a handheld switch
      while leaning voluntarily backward on a sole pressure analyzer and on a heel
      force plate. The large change was indicated at the center of heel pressure.
      Morphological features of the foot were measured on an X-ray film. The position
      of heel pressure center and the morphological locations were represented as
      relative distance (%) from the hindmost point of the heel, where foot length
      represented 100%. Center of heel pressure changed largely during backward
      leaning, and the position at which large change occurred was the same as that of
      the peak of the distribution. Large change in distribution of heel pressure was
      perceived at a position 1.3% posterior from that at which the large change
      actually occurred. The correlation between perceived and actual positions was
      significant (r = .91). Significant correlations were found between position of a
      large change of center and locations of heel pressure of both the lateral process
      of the calcaneal tuberosity and the top of the talar trochlea (r = .86; r = .71,
      respectively). The results indicate that subjects accurately perceive large
      changes in distribution of heel pressure and that the morphological features of
      the foot contribute to these changes.

PMID- 15974355
TI  - Preschool children's accumulated and sustained physical activity.
AB  - 39 3- to 5-year-old children wore heart-rate monitors for 12 hr. on three
      consecutive days to examine physical activity patterns. Parent logs supplied
      additional information on type and location of activity. The highest number of
      accumulated minutes of moderate to vigorous physical activity was recorded during
      the weekday (38.6 min.) and weekend (31.4 min.) afternoons, a time period when
      more activity occurred outdoors. Sustained activity was mostly short in duration,
      but many children (71%) accumulated recommended amounts of activity on the
      weekday, fewer (46%) on the weekend. Spearman rank correlations for weekday
      (r=.50, p=.004) and weekend (r=.58, p=.004) activity were significant.
      Considering health risk factors associated with physical inactivity, early
      educators must look to the essence of young children's physical activity patterns
      in designing programs. Large motor activity that is intense and that occurs
      outdoors is a good place to start.

PMID- 15974356
TI  - An exploratory study of cognitive style in performance on matched and mismatched
      tasks.
AB  - Researchers have suggested that task performance is often dependent upon the
      congruence of cognitive style and task. To explore this suggestion, 44 female and
      4 male undergraduates were administered the Cognitive Style Analysis, the Closure
      Flexibility, the Composite Gestalt Completion Test, and the Vocabulary subtest
      from the WAIS. Specifically, four hypotheses were tested: (1) that participants
      with an analytic style will perform better than those with a wholistic style on
      the Closure Flexibility; (2) that participants with a wholistic style will
      perform better than those with an analytic style on the Composite Gestalt
      Completion Test; (3) that participants with an intermediate style will outperform
      persons with an analytic style on the Composite Gestalt Completion Test; and (4)
      that intermediate scorers would perform better than those with a wholistic style
      on Closure Flexibility. Only the second hypothesis was supported, so results
      provide only minimal support for the effect of match or mismatch of cognitive
      style and task performance.

PMID- 15974357
TI  - Correlates of Children's Eating Attitude Test scores among primary school
      children.
AB  - A total of 107 Malay primary school girls (8-9 yr. old) completed a set of
      measurements on eating behavior (ChEAT, food neophobia scales, and dieting
      experience), the Rosenberg Self-Esteem Scale, body shape satisfaction, dietary
      intake, weight, and height. About 38% of the girls scored 20 and more on the
      ChEAT, and 46% of them reported dieting by reducing sugar and sweets (73%),
      skipping meals (67%), reducing fat foods (60%) and snacks (53%) as the most
      frequent methods practiced. In general, those girls with higher ChEAT scores
      tended to have lower self-esteem (r=.39), indicating they were more unwilling to
      try new foods (food neophobic) (r=.29), chose a smaller figure for desired body
      size (r=-.25), and were more dissatisfied with their body size (r=.31).

PMID- 15974359
TI  - Nine, seven, five, or three: how many figures do we need for assessing body
      image?
AB  - 320 Croatian female students (M=20.4 yr.) were recruited to examine the validity
      and reliability of figural scales using different numbers of stimuli (3, 5, 7,
      and 9) and different serial presentation (serial and nonserial order). A two-way
      analysis of variance (4 numbers x 2 orders of stimuli) was performed on ratings
      of current self-size and ideal size as dependent variables. Analysis indicated a
      significant main effect of number of stimuli. This, together with post hoc tests
      indicated that ratings were significantly different for a scale of three figures
      from scales of more figures, which in turn did not differ among themselves. Main
      effects of order of stimuli, as well as the interaction, were not significant.
      The results support the hypothesis that the optimal number of figures on a scale
      is seven plus (or minus) two.

PMID- 15974358
TI  - Changes in cognitive performance during a 216 kilometer, extreme endurance
      footrace: a descriptive and prospective study.
AB  - Two subjects participated in a 216 km ultramarathon with outside temperatures
      above 50 degrees C while several physiological and psychological parameters
      (cognitive performance assessed by a mental calculation task and an attentional
      task, subjective bodily experience, and lactate level) were evaluated throughout
      the race. Severe stress from dehydration, sleep deprivation, and total physical
      exhaustion are combined in a unique manner, allowing evaluation of their effects
      in a range far outside that obtainable in a laboratory setting. During the race
      the subjects answered a questionnaire about their actual bodily experiences,
      underwent 8 medical examinations, and performed two cognitive tests approximately
      every 35 kilometers. Analysis showed cognitive performance did not decrease
      steadily in a simple and gradual way but reached a peak in the morning of Day 2
      after a short sleeping period and then decreased. In the early morning of Day 3,
      in general cognitive performance exhibited the worst results but increased
      differentially between the subjects again in the last test 1 km before the finish
      line.

PMID- 15974360
TI  - Effects of caffeine on the trigeminal blink reflex.
AB  - The acoustic startle and trigeminal blink reflexes share the same motor output.
      Since caffeine has been shown to augment the startle reflex, it was proposed that
      caffeine would also increase the trigeminal blink reflex. In 6 humans, the
      effects of caffeine (100 mg) on the trigeminal blink reflex were investigated.
      Reflex blinks were elicited by stimulation of the supraorbital branch of the
      trigeminal nerve. Following ingestion of caffeinated coffee, reflex blinks
      increased in amplitude and duration and occurred at a shorter latency than reflex
      blinks following ingestion of decaffeinated coffee. Since the blink reflex is a
      brainstem reflex, these results suggest that the psychomotor effects of caffeine
      facilitate brainstem processing.

PMID- 15974361
TI  - Motivational climate, achievement goals, perceived sport competence, and
      involvement in physical activity: structural and mediator models.
AB  - Students (N=231) were tested on involvement in physical activity, motivational
      climate, perceived sport competence, and goal orientations. Multiple regression,
      partial correlation, and LISREL analyses indicated that mastery goal adoption is
      positively correlated with a mastery climate. Performance-approach goal adoption
      is positively correlated with a performance climate. Mastery climate, mastery
      goal, and perceived sport competence are all positively correlated with
      involvement in physical activity. LISREL analyses supported three mediational
      hypotheses: (I) the positive correlation between the performance-approach goal
      and involvement in physical activity is mediated by (high) perceived sport
      competence, (II) the negative correlation between the performance-avoidance goal
      and involvement in physical activity is mediated by (low) perceived sport
      competence, (III) the positive correlation between mastery climate and
      involvement in physical activity is mediated by (high) mastery goal orientation.
      An alternative structural model with perceived competence as the last latent
      construct in the path was also tested.

PMID- 15974362
TI  - Effects of regular switching between languages during random number generation.
AB  - Random number generation is a task that engages working memory and executive
      processes within the domain of number representation. In the present study we
      address the role of language in number processing by switching languages during
      random number generation (numbers 1-9), using German (L1) and English (L2), and
      alternating L1/L2. Results indicate large correspondence between performance in
      L1 and L2. In contrast to nonswitching performance, randomization with
      alternating languages showed a significant increase of omitted responses, whereas
      the random sequences were less stereotyped, showing significantly less repetition
      avoidance and cycling behavior. During an intentional switch between languages,
      errors in language sequence appeared in 23% of responses on the average,
      independently of the quality of randomization but associated with a clear
      persistence of L2. These results indicate that random number generation is more
      closely linked to auditory-phonological representation of numerals than to visual
      arabic notation.

PMID- 15974363
TI  - Effect of VDT keyboard height and inclination on musculoskeletal discomfort for
      wheelchair users.
AB  - This study investigated the effect of keyboard height and inclination on
      musculoskeletal discomfort for wheelchair users. Eight Taiwanese male wheelchair
      users (28.75 +/- 8.75 years) were recruited as participants to perform nine
      experimental combinations of data entry tasks. Three keyboard heights and three
      inclinations were evaluated. Musculoskeletal discomfort was estimated by Rating
      of Perceived Exertion and Subjective Preference Ranking. Each subject performed a
      data entry task for all nine experimental combinations in a random order. The
      seated posture of all participants during the data entry operation was the
      upright posture. The height of the screen's center was adjusted according to the
      eye level of each subject. Analysis showed the keyboard height and keyboard
      inclination significantly affected rating of musculoskeletal discomfort. It is
      suggested that the optimum keyboard height choice is elbow-level height or 5 cm
      below elbow level with the keyboard inclination horizontal to the seat of the
      wheelchair.

PMID- 15974364
TI  - Detection of invariants by haptic touch across age groups: rod length perception.
AB  - This study examined the development in the detection of maximum eigenvalues and
      static moment as invariants, through a task of perceiving rod length without
      visual information by haptic touch. 34 participants ages 6 to 83 years
      participated in the experiment. Their exploratory behavior and perceptions of rod
      length were analyzed by age group (Children: 6 to 12 years old; Young Adult: 21
      to 25 years old; Middle Age: 31 to 56 years old; and Older: 65 to 83 years old).
      A behavior analysis indicated that use of vertical swinging increased for the
      Young Adult group and decreased with age for the Older group, whereas Children
      frequently held the rod without wielding. Analysis showed that, by age,
      differences in coefficients on the maximum eigenvalue and static moment were
      parallel with an exploratory behavioral change. Finally, the effect of different
      exploratory behaviors on length perception was discussed.

PMID- 15974365
TI  - Inhibition of return using location discrimination in two age groups.
AB  - The present study investigated "inhibition of return" which refers to increased
      response latency when the target in a location discrimination task appears in the
      same location on consecutive trials. Research to date has suggested that this
      effect is little changed across age. However, this study, which compared 12 older
      adults in good health (M=73.0, SD=5.3) with younger adults using the target
      target paradigm to examine inhibition of return, suggests there is a strong and
      continuous effect in older adults in comparison to younger adults. Results
      indicate the possibility that the inhibitory function may become stronger at an
      older age.

PMID- 15974366
TI  - In search of dominance: the case of the missing dimension.
AB  - Some previous researchers have found that affect can be described in terms of two
      dimensions (pleasure and arousal), while others have noted three dimensions are
      needed (pleasure, arousal, and dominance). The competing claims were tested by
      creating stimuli with factors previously demonstrated to elicit responses of
      arousal or dominance, asking respondents to rate the stimuli, and contrasting
      correlations between ratings and the stimulus factors. Under the two-dimensional
      theory, the planned contrasts should be zero, while under the three-dimensional
      theory, the planned contrasts should be nonzero. Results supported the three
      dimensional model.

PMID- 15974367
TI  - Reliability and validity of a twelve-minute walking test for coronary heart
      disease patients.
AB  - This study examined the reliability and validity of a 12-min. walking test for
      coronary heart disease patients. CHD patients (28 men, 18 women) were recruited
      out of 86 CHD patients of the Martini Hospital Groningen, The Netherlands. 46 CHD
      patients (age M=66.0 yr., SD=6.8) participated in the reliability study and 24
      (age M=62.0 yr., SD=9.2) in the validity study. A test-retest analysis showed a
      satisfactory Bland-Altman plot and an intraclass coefficient of .98. The Pearson
      correlation between the score on the test and the VO2 peak was .77. This test
      gives a reliable and valid assessment of cardiorespiratory fitness of CHD
      patients.

PMID- 15974368
TI  - Comments on Abrahamsen's (2004) "Linguistic humor comprehension in children with
      articulation impairments".
AB  - This commentary expresses concerns about the validity of the results of
      Abrahamsen's study of "Linguistic humor comprehension in children with
      articulation impairments" (2004). Some of the problems noted included overlapping
      of lexical and phonological humor categories, the nature and placement of several
      of the stimulus items, lack of demonstrated equivalent difficulty of the stimuli
      presented to each group, and limited analysis of other factors that may have
      affected children's responses.

PMID- 15974369
TI  - Psychological traits and behavioral coping of psychiatric consumers: the
      mediating role of self-esteem.
AB  - A positive coping style can be critical to successful rehabilitation of
      psychiatric consumers. Using structural equation modeling, this study examined
      the relationships among consumers' psychological characteristics, self-esteem,
      and behaviors, and the role of self-esteem in mediating the relationships between
      psychological characteristics and behavioral coping. The sample consisted of 393
      psychiatric consumers recruited from 25 psychosocial rehabilitation services
      (PSR) agencies. Key findings were that affective (that is, negative and positive
      affect) and cognitive (that is, beliefs in devaluation-discrimination) traits
      influence self-esteem and behavioral coping, and significant effects of affective
      and cognitive traits on behavioral coping are mediated by self-esteem. The
      findings suggest that interventions targeting self-esteem could be effective in
      modifying the behavioral coping of consumers served in PSR agencies. Implications
      for social work practice are discussed in relation to attitude change theories.

PMID- 15974370
TI  - Evidence-based assessment in case management to improve abnormal cancer screen
      follow-up.
AB  - The authors describe an evidence-based assessment protocol for intensive case
      management to improve screening diagnostic follow-up developed through a research
      project in breast and cervical cancer early detection funded by the Centers for
      Disease Control and Prevention. Three components of an evidence-based approach to
      assessment are presented and illustrated in the Screening Adherence Follow-up
      (SAFe) protocol: (1) evidence for known risks and barriers for the target
      population; (2) standardized assessment elements; (3) evidence for the accuracy,
      efficiency, and validity of the protocol in use. Testing of the assessment tool
      in a pilot study of more than 600 women demonstrated practical utility in
      matching assessed needs with service intensity and confirmed that differential
      amounts of service and different provider effort achieved equally satisfactory
      adherence results. The evidence-based components described and the types and
      nature of evidence on which they draw can be generalized to new settings and
      client concerns.

PMID- 15974371
TI  - Communication between older people and their health care agents: results of an
      intervention.
AB  - This study examined an intervention to help high-functioning community-dwelling
      older people communicate their wishes for care at the end of life with someone
      they would trust to make health care decisions for them if necessary. Groups
      consisted of dyads of older people and their potential or designated health care
      agents randomly assigned to the intervention (STEP program) or control group.
      STEP participants received three group sessions with educational and support
      components. For individual participants, there was a statistically significant
      difference between groups on knowledge of the health care proxy form and the
      roles and responsibilities of the agent. For the dyads of older people and their
      agents, there was a significantly higher mean communication score for the STEP
      participants than for the control group. The findings demonstrate that it is
      possible to affect advance communication about wishes at the end of life through
      a group intervention.

PMID- 15974372
TI  - Social Work Admission Assessment Tool for identifying patients in need of
      comprehensive social work evaluation.
AB  - Early identification of patients who need a social work evaluation is integral to
      effective discharge planning. This article describes the development and
      application of the Social Work Admission Assessment Tool (SWAAT), a six-item
      scale that identifies patients with complicated discharge needs who require a
      social work evaluation. It addresses ambulation, mental status, living situation,
      current social services, self-perceived need for additional services, and need
      for assistance in going home. Based on their scores, patients are categorized as
      having low, intermediate, or high need. A greater proportion of high-need
      patients were discharged with services and had prolonged hospitalizations (p =
      .0001). The SWAAT is a comprehensive needs assessment tool that may facilitate
      discharge planning and improve quality of care.

PMID- 15974373
TI  - Ethical considerations in prenatal sex selection.
AB  - Developments in assisted reproductive technologies have made it possible for
      couples to select the sex of a child prenatally. This article used the NASW Code
      of Ethics and information from the Ethics Committee of the American Society of
      Reproductive Medicine to consider ethical dilemmas related to social justice (for
      example, reinforcement of gender bias, the potential for gender discrimination
      and oppression, a move toward eugenics, restricted access based on social or
      economic status, and the discarding of human embryos), the importance of human
      relationships (for example, threats to the well-being of sex-selected children,
      parent-child relationships, and couple relationships), and self-determination and
      the dignity and worth of the individual (for example, the right of individuals or
      couples to choice and personal desires). Implications are discussed for social
      work practice, policy articulation and advocacy, research, and education.

PMID- 15974374
TI  - Cultivating social work leadership in health promotion and aging: strategies for
      active aging interventions.
AB  - The rapid growth of the population of older adults and their concomitant physical
      status and health needs have captured the attention, collaboration, and funding
      support of an array of leaders in the fields of aging and health care. To help
      fill the void of literature available to social workers interested in health
      promotion and aging, the authors provide a conceptual clarification of the
      meaning of health and explain how health is a resource for optimal living and not
      merely the absence of disease. The authors analyze frameworks of health promotion
      and suggest that the ecological approach provides the ideal framework for
      devising successful strategies in the area of aging. Finally, using the example
      of promoting physical activity as a healthy aging strategy, they detail eight
      ways that social workers can provide leadership in promoting positive health in
      later life.

PMID- 15974375
TI  - Adaptation to long-term prostate cancer survival: the perspective of elderly
      Asian/Pacific Islander wives.
AB  - Increasingly evident is the important role of partners in patients' adaptation to
      diagnosis, treatment, and recovery. Yet, little is known about partners'
      adaptation when patients reach the benchmark known as long-term survival. This
      study describes elderly wives of prostate cancer survivors' perspectives of
      adaptation to the enduring challenges of prostate cancer survival and considers
      their experience in the context of ethnicity. Content analysis and grounded
      theory methods guided data collection and analysis of two waves of in-depth
      interviews with 26 elderly Asian/Pacific Islanders (Chinese, Filipino, Japanese,
      Native Hawaiian) living in Hawai'i. Continuous learning was the most common
      phenomenon as reflected in four types of adaptive work: involvement in husband's
      health, affirmation of the marital bond, normalization of adversity, and
      participation in personally meaningful acts. Issues are highlighted for
      consideration in developing culturally relevant, age-appropriate, and strengths
      based interventions.

PMID- 15974376
TI  - A longitudinal look at social work leadership in hospitals: the impact of a
      changing health care system.
AB  - This article examines the responses of social work administrators to the changes
      occurring throughout their hospitals over three time periods in the 1990s; the
      major accomplishments of social work services in their facilities; and the
      failures, frustrations, and obstacles in the delivery of social work services. It
      compares the reports of social work director cohorts on the changes they
      experienced over an eight-year period with what they had expected in their
      settings. It also analyzes their perceptions over time of obstacles and
      opportunities for hospital social work administrators in response to these
      changes. The authors present the ways in which social work administrators
      understand and address the complexities they face.

PMID- 15974377
TI  - Asthma management: a role for social work.

PMID- 15974378
TI  - Why Kerry lost and where we go from here.

PMID- 15974380
TI  - Possible new career options.

PMID- 15974381
TI  - Superstitions among perioperative nurses.
AB  - A descriptive study was conducted using a mailed questionnaire to determine the
      prevalence of work-related superstitions among perioperative nurses. Data
      analysis included the two-sample t test for continuous data and the two-sided
      Fisher's exact test for binary data. Study results indicate that although only
      23% of respondents view themselves as "generally superstitious," specific work
      related superstitions are widespread. Belief in specific superstitions was not
      statistically related to age or number of years as a perioperative nurse. An
      analysis of the literature on medical workplace superstitions helps to elucidate
      possible underlying explanations for the phenomenon of nursing superstitions.

PMID- 15974382
TI  - Predicting and preventing pressure ulcers in surgical patients.
AB  - Pressure ulcers, regardless of their origin, represent negative outcomes for
      patients, including pain, additional treatments and surgery longer hospital
      stays, disfigurement or scarring, increased morbidity, and increased costs. The
      or is a high-risk environment for the development of pressure ulcers.
      Preoperative identification of patients at risk for pressure ulcer development is
      imperative if cost-effective, evidence-based preventive measures are to be
      implemented. This article presents a review of the literature pertaining to
      pressure ulcer development in surgical patients. Recommendations for future
      research and implications for practice are provided.

PMID- 15974383
TI  - Surgical instrument availability.
AB  - Surgical instrument availability often is at the top of the list for
      perioperative quality improvement projects. Ensuring availability of surgical
      instruments can be a daily struggle. At one facility, searching for items shortly
      before a procedure was a common occurrence. This article describes a three-year
      quality improvement project undertaken to improve instrument availability
      throughout surgical services. The article also includes future plans and lessons
      learned.

PMID- 15974384
TI  - Patients' perceptions of emotional support and information provided to family
      members.
AB  - The purpose of this quality improvement project was to determine patients'
      perceptions of the emotional support and information provided to their family
      members by nurses in a day surgery setting. The project was conducted in a day
      surgery unit of a hospital in western Finland. Data were collected from 60
      participants using a questionnaire designed specifically for the project. The
      results showed that half of the patients appreciated the presence of their family
      members during hospital care. The emotional support provided to family members
      was rated as moderate, and more than 50% of the patients believed their family
      members were adequately informed. The results were used to help develop tools for
      patient and family member education.

PMID- 15974385
TI  - Staffing ratio trends--a survey of perioperative nurse managers.
AB  - Current data from perioperative practice areas can help determine appropriate
      ratios for the skill mix of employees in perioperative settings. For this survey,
      managers were asked to report staffing ratios and other facility information to
      identify current trends. A ratio of two RNs to one surgical technologist was most
      commonly reported. This is consistent across several factors, including practice
      area, number of ORs, and number of procedures.

PMID- 15974386
TI  - Patient advocacy--nurses keeping patients safe.

PMID- 15974387
TI  - AORN guidance statement: safe on-call practices in perioperative practice
      settings. Association of periOperative Registered Nurses.
AB  - Call staffing and the associated long work hours can be challenging for both
      perioperative staff members and the health care organization. A change in culture
      is needed to recognize exhaustion as an unacceptable risk to patients and
      perioperative personnel safety. Perioperative health care providers have a
      personal responsibility to arrive at work fully rested. Health care organizations
      have a responsibility to create work and call schedules that consider the effect
      of long work hours on patient safety as well as perioperative staff members'
      welfare. The development of standardized safe work hours and call practices
      should reflect current recommendations emerging from authoritative sources,
      legislation, and empirical data. Prolonged work periods without adequate rest may
      contribute to diminished performance by perioperative personnel, placing both
      patients and workers at risk. This guidance statement may assist managers and
      clinicians in developing policies and procedures for safe call practices.

PMID- 15974388
TI  - AORN guidance statement: perioperative staffing. Association of periOperative
      Registered Nurses.
AB  - One of the most important responsibilities of a perioperative nursing leader is
      the development of an effective staffing plan relative to surgical patients'
      needs. AORN recognizes there are a variety of settings in which perioperative RNs
      practice. This guidance statement is intended to serve as a guide for
      perioperative nursing leaders in developing a staffing plan and is designed to be
      adaptable to various practice settings.

PMID- 15974389
TI  - AORN guidance statement: Fire prevention in the operating room.

PMID- 15974391
TI  - Buying into practices. Three hospitals announce deals covering 300 docs.

PMID- 15974390
TI  - Nurse in Washington interns share their experiences and insight.

PMID- 15974392
TI  - Reigniting the charge for IT. Leavitt will spearhead federal effort to develop
      national healthcare IT network, but question remains: who will pay?
AB  - HHS Secretary Mike Leavitt, left, confronted the IT challenge last week by
      announcing he will oversee efforts to establish a nationwide healthcare IT
      system. "I believe we have to transform healthcare just as the railroads
      transformed transportation in America," Leavitt said, when announcing his plans
      at a HIMSS meeting. His new advisory committee, the American Health Information
      Community, will help set standards.

PMID- 15974393
TI  - Certification concerns. Group seeking EHR contract got vendor donations.

PMID- 15974394
TI  - Catching the ownership wave. Hawaiian docs seek to buy struggling hospitals.

PMID- 15974395
TI  - Family tension. AMA support for specialty hospitals irks members.

PMID- 15974396
TI  - Moody's: let's size up boards.

PMID- 15974397
TI  - One more down for HealthSouth.

PMID- 15974398
TI  - Uninsured concerns grow. Studies show costs of problem, but will D.C. act?

PMID- 15974399
TI  - Bon Secours bounces back. System gets back to basics and soothes rating agency.

PMID- 15974400
TI  - Purchasing. Second audit finds same woes.

PMID- 15974401
TI  - Lighting a fire under IT. Leavitt steps in to revive effort that seemed to be
      faltering.

PMID- 15974402
TI  - Workforce report 2005. Losing their faculty. Nursing schools are turning away
      applicants as RNs are lured by higher salaries outside academia.

PMID- 15974403
TI  - Workforce report 2005. Doc shortage gets noticed.

PMID- 15974404
TI  - Workforce report 2005. Snapshot 2005: the workforce shortage by the numbers.

PMID- 15974405
TI  - Workforce report 2005. Bracing for Medicaid cuts. Nursing homes fear workforce
      relief may be brief.

PMID- 15974406
TI  - Workforce report 2005. Nurses gain on ratios. Judge overturns order to relax
      rules.

PMID- 15974407
TI  - Rural health. The MMA giveth... Changes to Medicare are boosting payments to
      rural hospitals, but some provisions of the law might prove to be troublesome.

PMID- 15974408
TI  - Making the publishing process transparent.

PMID- 15974409
TI  - A raised profile and a clearer vision: testimonies of two winners.

PMID- 15974410
TI  - Developing an accurate system of measuring colour in a venous leg ulcer in order
      to assess healing.
AB  - OBJECTIVE: To develop a standardised method of assessing venous ulceration, based
      on the colour of an ulcer bed and the surrounding skin. METHOD: This pilot study
      involved taking three sequential digital photographs during an episode of care
      and measuring the colour using image analysis software. Ten episodes of care were
      used for data collection. RESULTS: Based on previous research, a threshold of <
      or =3 degrees of colour and 3% of saturation was selected to indicate the
      reliability of the system. The mean of the colour measurements was inside the
      reliability threshold when measuring an ulcer bed, but outside the threshold for
      measuring the surrounding skin. CONCLUSION: The results indicate that the system
      provides consistent visual representation of a venous leg ulcer.

PMID- 15974411
TI  - Colloid or crystalloid for resuscitation of major burns.
AB  - There is continuing debate over the merits of colloid versus crystalloids for the
      resuscitation of major burns. This article reviews fluids used in burn
      resuscitation and discusses potential advantages and disadvantages of colloid and
      crystalloid.

PMID- 15974412
TI  - Antibiotic treatment of infected diabetic foot ulcers.
AB  - Antimicrobial treatment can be effective in diabetic foot ulcers. However,
      choosing the appropriate regimen depends on the clinical and microbial
      presentation. This review describes the factors practitioners need to consider.

PMID- 15974413
TI  - Compression and peri-ulcer skin in outpatients' venous leg ulcers: results of a
      French survey.
AB  - OBJECTIVE: To evaluate concordance with compression therapy in ambulatory
      patients with venous leg ulcers. METHOD: This was a prospective observational
      survey conducted in general practice. Consecutive patients with venous leg ulcers
      about to receive a non-adherent primary dressing and with no contraindication to
      compression bandaging were selected. At the inclusion visit, size, local aspect
      of the ulcer and the peri-ulcer skin were scored. Patients were asked about
      concordance with compression and were given a questionnaire to be completed at
      home. If patients were seen at a three-week follow-up visit, ulcer and peri-ulcer
      characteristics and concordance were reassessed. RESULTS: A total of 2842
      patients were included, of whom 2532 were re-evaluated at three weeks and 1397
      (49%) returned their questionnaire. A compression bandage was already available
      for 62.9% of these patients, and 62.7% said they used it on a daily basis, 23.3%
      wore it one or two days per week and 13.7% wore it irregularly or never. There
      was a statistically significant correlation between concordance with compression
      and ulcer and peri-ulcer skin severity scores (p < 0.001 and p = 0.042
      respectively). At the follow-up visit, concordance with compression therapy
      improved (80.1% were wearing it regularly). Ulcer, peri-ulcer skin severity
      scores and ulcer size were significantly lower (p < 0.001) when concordance with
      compression therapy was good. However, 65.6% of patients considered applying
      compression very difficult; 45% considered it very unaesthetic and 23% judge
      wearing it to be very painful, while 9% thought it may worsen their ulcer.
      CONCLUSION: On a short-term basis, concordance with compression can be
      substantially improved by simple measures with a clear favourable consequence on
      both ulcer status and peri-ulcer skin aspect when a non-adherent primary dressing
      is used. However, the acceptability of compression to patients is poor, and
      continuous effort is required to convince them of its importance.

PMID- 15974414
TI  - Winter's concept of moist wound healing: a review of the evidence and impact on
      clinical practice.
AB  - Winter's concept of moist wound healing has had a major influence on wound care
      practice. This paper reviews the literature and demonstrates that the underlying
      wound healing process is complex and still not fully understood.

PMID- 15974415
TI  - Effect of glycaemic control on apoptosis in diabetic wounds.
AB  - OBJECTIVE: To study the effect of glycaemic control on apoptosis in chronic
      ulcers in diabetic patients and the differential roles of insulin and oral
      hypoglycaemic agents (OHAs). METHOD: Ten non-diabetic (group I) and 20 diabetic
      patients (groups II and III), with a wound of more than four weeks' duration, who
      were attending the wound clinic at University Hospital, Varanasi, India were
      recruited. The 10 patients in group 11 received insulin and the 10 in group III
      an oral hypoglycaemic agent; all had diabetic foot ulcers. Wound biopsy and other
      routine investigations were performed. Both DNA fragmentation and morphological
      changes under light microscopy (apoptotic index) were used as determinants of
      apoptosis. Different variables, including fasting and post-prandial blood sugar,
      serum low-density lipoprotein (LDL) and markers of microangiopathy, such as
      proteinuria and diabetic retinopathy, were compared with apoptosis. RESULTS: DNA
      fragmentation in groups I, II and III was 40.00 +/- 2.97, 45.26 +/- 3.21 and 60.8
      +/- 3.13 respectively (p < 0.01). Near linear correlation was observed with blood
      sugar level, particularly post-prandial blood sugar (p < 0.05) and DNA
      fragmentation. DNA fragmentation was significantly correlated with serum LDL and
      proteinuria, and it was much greater in the OHA group than in the insulin group
      (p < 0.05). Similarly, in the diabetic patients with background retinopathy the
      DNA fragmentation was 46.50 +/- 3.42 (n=3) in the insulin group and 66.70 +/-
      6.48 (n=4) in the OHA group (p < 0.05). CONCLUSION: There is a significant
      increase in apoptosis in diabetic wounds with poorly controlled blood sugar and
      microangiopathy. This increase was greater in patients on OHAs than those on
      insulin, and it contributes to delayed wound healing. Morphological markers do
      not appear to be a reliable index of apoptosis in the diabetic wound.

PMID- 15974416
TI  - The role of fibronectin in fibroblast migration during tissue repair.
AB  - Fibronectin is known to stimulate cell growth and migration, but research does
      not provide a complete picture of all the mechanisms involved. Further studies
      are needed before practitioners can apply in vitro results to in vivo
      environments.

PMID- 15974417
TI  - Study to determine the efficacy of topical morphine on painful chronic skin
      ulcers.
AB  - OBJECTIVE: To assess the efficacy of the topical application of morphine on
      painful chronic skin ulcers. METHOD: A prospective bi-centric controlled double
      blind randomised study was conducted involving 24 patients with painful chronic
      skin ulcers using topically applied morphine versus placebo. Ten milligrams of
      morphine hydrochloride with Intrasite Gel or Intrasite Gel with placebo were
      applied daily for five days. All patients were treated with a level II analgesic
      treatment. A numeric pain scale lower than 4/10 and no need for a 'rescue'
      treatment (morphine sulphate) indicated that the treatment was successful. Local
      and systemic tolerance of the treatments was analysed daily. RESULTS: Twenty-four
      patients were included in the study, but only 18 started the protocol. Only 2/11
      patients were completely relieved in the morphine group compared with 1/7 in the
      placebo group. Local and general tolerance of morphine was good. The peripheral
      efficacy of morphine is under discussion. CONCLUSION: The results suggest that
      topical morphine cannot be an alternative to morphine administered by other
      routes (subcutaneously or orally) in painful chronic skin ulcers. Stimulation of
      peripheral morphine receptors by systemic morphine could explain the difference
      between these results and those of previous studies.

PMID- 15974418
TI  - Therapist style in sexual offender treatment: influence on indices of change.
AB  - This paper describes the results of our review of the broad process literature as
      well as summarizing two studies examining the influence of the therapist in
      generating changes in treatment targets among sexual offenders. We conclude that
      displays of empathy and warmth by the therapist as well as the provision of
      rewards for progress and some degree of directiveness, maximize the benefits
      derived from the procedures employed in treating sexual offenders. We also
      suggest the need for flexibility and encourage program designers not to so overly
      detail their treatment manuals that the influence of the therapist is minimized.

PMID- 15974419
TI  - Research on the processes involved in treating sexual offenders.
AB  - This article summarizes preliminary findings from a series of pilot studies on
      the processes involved in treating sexual offenders. Quantitative and qualitative
      methods were used on samples of 15 to 24 child molesters undergoing a prison
      based cognitive-behavioral and relapse prevention treatment program. Results are
      presented and discussed in the form of 5 questions: (1) Are therapists just
      "technicians"? The offenders' point of view (2) Does confronting the therapist
      mean treatment resistance? (3) Are the therapists perceived as therapists,
      parents, or a bit of both? (4) Is the structure of the program important? The
      offenders' point of view and (5) Is a sense of mastery important in a prison
      setting? It is suggested that researchers investigate the processes underlying
      the treatment of offenders, especially the common factors which have been shown
      to have an effect on therapeutic outcome.

PMID- 15974420
TI  - Relationship between therapeutic climate and treatment outcome in group-based
      sexual offender treatment programs.
AB  - The aim of the study was to examine the relationship between therapeutic climate
      and the effectiveness of CBT treatment for sexual offenders in U.K. prisons. To
      this end a measure of group atmosphere was administered to members and leaders of
      12 treatment groups running the same prison-based sexual offender treatment
      program. Treatment outcome was measured using a case-by-case methodology
      clinically significant change analysis--to identify the percentage of individuals
      within each group who had significantly changed on measures of pro-offending
      attitudes targeted in treatment. The results of the group process measure
      indicated leaders generally viewed groups more positively than members. Clear
      differences were also found between groups (ostensibly running the same treatment
      program) in terms of group climate. Analysis of members' process data indicated
      that there was a clear relationship between how cohesive the members reported the
      group to be and the extent to which freedom of action and expressions of feelings
      were encouraged in groups, as well as treatment outcome as measured by
      significant reductions in pro-offending attitudes. These results are discussed in
      terms of what they say about attitudes and goals of those involved in running
      treatment and how the effectiveness of treatment programs can be maximized.

PMID- 15974421
TI  - What happens in therapy with sexual offenders? A model of process research.
AB  - This paper presents two studies (one single case and one comparative study)
      examining change processes within individual therapy sessions as well as during
      the course of treatment. The Therapeutic Cycle Model (TCM), developed for general
      psychotherapy to objectify change events in the course of psychotherapies, is
      applied to transcribed tape recordings of therapy sessions with sexual offenders.
      The TCM focuses on emotional experience and cognitive mastery and uses computer
      assisted text analysis. In addition to the TCM approach clinical ratings are used
      as independent criteria. The predicted relationship between the phases of the TCM
      and scores on the respective scales of the clinical ratings were supported.

PMID- 15974422
TI  - The utility of the Trans-theoretical Model of Behavior Change in the treatment of
      sex offenders.
AB  - This paper discusses the use of the Trans-theoretical Model of Behavior Change in
      the treatment of sex offenders. Constructs within this theory are the Stages of
      Change, Processes of Change and Decisional Balance. The first section of this
      paper provides a brief description of these constructs. The second section
      provides a brief review of research related to these constructs and discusses the
      implications of this research in relation to the treatment of sex offenders. The
      third section of this paper provides a practical description of the use of the
      constructs of the Trans-theoretical Model of Behaviour Change in the treatment of
      sex offenders. Although the validity of this model among sex offenders requires
      further investigation, the Trans-theoretical Model of Behavior Change appears to
      have considerable utility as an overarching theoretical model to conceptualize
      and facilitate behavior change among sex offenders.

PMID- 15974423
TI  - Testosterone, sexual offense recidivism, and treatment effect among adult male
      sex offenders.
AB  - The relationship between serum testosterone and sexual violence was examined in a
      sample of 501 convicted adult male sex offenders attending an intensive in
      hospital group psychotherapy treatment program. It was found that men with higher
      testosterone tended to have committed the most invasive sexual crimes (p < .001,
      two-tailed). Further, a positive partial correlation (controlling for age)
      between testosterone and sexual offense recidivism over a lengthy follow-up
      period (mean = 8.9 years) was found. When the sample was separated into one group
      that completed treatment and one group that did not, an important ameliorating
      treatment effect was observed. Although controlling for age, serum testosterone
      remained significantly predictive of sexual recidivism for the treatment
      noncompleter group (p < .05, two-tailed). For those who completed treatment
      testosterone was no longer predictive of sexual reoffense (p > .05, two-tailed).
      Among convicted sex offenders, higher serum testosterone appears to be associated
      with greater likelihood of further sexual violence. Effective therapy, however,
      appears able to intercede in the influence of testosterone on sexually deviant
      behavior. It is suggested that serum testosterone may be an informative static
      risk factor and completion of intensive treatment should be accorded significance
      in future actuarially based risk prediction instruments.

PMID- 15974424
TI  - Do child molesters deliberately fake good on cognitive distortion questionnaires?
      An information processing-based investigation.
AB  - Researchers and clinicians hypothesize that child molesters hold offence
      supportive beliefs or cognitive distortions that require restructuring for
      successful rehabilitation. However, there is little empirical evidence to support
      this hypothesis. Current questionnaire measures of both untreated and treated
      child molesters' cognitive distortions show that these men typically disagree
      with cognitive distortions. Such findings, especially prior to treatment, are
      often interpreted to mean that child molesters are faking good. In this study we
      drew on personality-related research showing that when participants intentionally
      respond in a socially desirable way on questionnaires, they make faster item
      responses than when answering honestly. Untreated child molesters, treated child
      molesters, and two types of controls (nonsexual offenders and nonoffenders) were
      administered a computerized cognitive distortion questionnaire and their
      responses and response times were recorded. Consistent with previous research,
      all groups tended to disagree with the cognitive distortions. However, response
      time data were surprising; only the treated child molesters displayed the fake
      good pattern of responding significantly faster in rejecting cognitive
      distortions. We speculate about the implications of these results for the
      cognitive distortion hypothesis, and for understanding how current treatment
      programs effect cognitive distortion change.

PMID- 15974425
TI  - The criminal histories and later offending of child pornography offenders.
AB  - The likelihood that child pornography offenders will later commit a contact
      sexual offense is unknown. In the present study, we identified a sample of 201
      adult male child pornography offenders using police databases and examined their
      charges or convictions after the index child pornography offense(s). We also
      examined their criminal records to identify potential predictors of later
      offenses: 56% of the sample had a prior criminal record, 24% had prior contact
      sexual offenses, and 15% had prior child pornography offenses. One-third were
      concurrently charged with other crimes at the time they were charged for child
      pornography offenses. The average time at risk was 2.5 years; 17% of the sample
      offended again in some way during this time, and 4% committed a new contact
      sexual offense. Child pornography offenders with prior criminal records were
      significantly more likely to offend again in any way during the follow-up period.
      Child pornography offenders who had committed a prior or concurrent contact
      sexual offense were the most likely to offend again, either generally or
      sexually.

PMID- 15974426
TI  - Post-conviction sex offender polygraph examination: client-reported perceptions
      of utility and accuracy.
AB  - Post-conviction polygraph testing of adult sex offenders in treatment has been a
      somewhat controversial subject. This study (n = 95 participants who took 333
      polygraph tests) explored how sexual offenders enrolled in outpatient treatment
      programs perceived their polygraph experience. Participants reported a relatively
      low incidence of false indications of both deception (22 of 333 tests) and
      truthfulness (11 of 333) tests, suggesting that clients agreed with examiners'
      opinions 90% of the time. The majority of clients reported that polygraph testing
      was a helpful part of treatment. Finally, about 5% of participants reported that
      they responded to allegedly inaccurate accusations of deception by admitting to
      things they had not done. The data offer encouragement for continued but cautious
      use of polygraphs by sex offender treatment programs. Implications for practice
      and research are identified.

PMID- 15974427
TI  - The Muskegon Access Health "Three-Share" plan: a case history.

PMID- 15974428
TI  - HPCSA.

PMID- 15974429
TI  - Maxillary sinus pathology in 119 patients--a histopathologic study.
AB  - INTRODUCTION: Information on histopathological changes within sinus mucosa is
      lacking, both in the general population, and in subjects with specific facial
      morphology and chronic respiratory obstruction. AIMS AND OBJECTIVES: To provide
      baseline data of the frequency and nature of pathological changes in the
      maxillary sinus in a specified group of patients. METHODS: 119 patients
      undergoing elective maxillary osteotomies were selected. These included patients
      with (70) and without (49) vertical maxillary excess (VME), and mouth and nasal
      breathers. The frequency and nature of the histopathological changes within the
      maxillary antral lining were recorded. RESULTS: Patients ranged from 13 to 47
      years, with a M:F ratio of 1:2.4. The findings included congestion (95%),
      submucosal oedema (90%), retention cysts (26%), true polyps (4.6%) and
      inflammation. There was eosinophilia (68%), basement membrane thickening (28%),
      goblet cell hyperplasia (95%) and dystrophic calcification (59%). CONCLUSIONS: A
      significant degree of sinus pathology was found in this specified group of
      patients. This was probably due to their living in a polluted urban environment.
      In the presence of such widespread pathological changes and the virtual
      impossibility of obtaining "normal" control tissue, investigators may find it
      impossible to correlate maxillary sinus pathology with either facial form or
      breathing pattern.

PMID- 15974430
TI  - Does mechanical pressure force bacteria into the dentinal tubules of carious and
      non-carious teeth--an exploratory study.
AB  - BACKGROUND: Although many researchers have confirmed bacterial migration within
      dentine, no evidence was found to show whether bacteria can be easily forced into
      dentine during caries treatment. OBJECTIVES: This exploratory study was to see if
      bacteria could be easily forced into dentinal tubules of carious and non-carious
      teeth using hand excavation and air pressure. METHODS: Two (2) carious and ten
      (10) non-carious teeth were used. Class I (Black's Classification) cavities were
      created using rotary instruments in the non-carious teeth, while the carious
      teeth were excavated using hand instruments to remove the caries. The cavity of
      one carious tooth was etched and in the other tooth was not. Five (5) of the non
      carious tooth cavities were etched, of which, one tooth was also disinfected. The
      remaining five non-carious teeth were not etched and included one tooth that was
      disinfected. Bacterial cultures of S. mutans, E. coli and Veilonella were placed
      in the prepared cavities and hand excavators and air pressure were used in an
      attempt to force bacteria down into the dentinal tubules. Thereafter, the teeth
      were fixed, decalcified and prepared for electron or light microscopy. RESULTS:
      One etched, and one etched and disinfected non-carious tooth showed bacteria in
      the dentinal tubules. One carious tooth (etched) showed bacterial presence in the
      dentinal tubules. CONCLUSION: This study shows that it is difficult to force
      bacteria into dentinal tubules using hand excavation (as in the Atraumatic
      Restorative Treatment technique) so a definitive study is not indicated.

PMID- 15974431
TI  - A review of candida and periodontal disease in immunocompetent and HIV-infected
      subjects.
AB  - The role of candida in the aetiology and pathogenesis of periodontal diseases is
      unclear. In spite of the organism being present in subgingival biofilm samples
      and in gingival biopsy specimens taken from affected subjects, it has not been
      possible to demonstrate that it is an active agent in these cases. There is an
      increase in the prevalence of candida species in the oral cavities and
      specifically in the subgingival biofilm of HIV-seropositive patients. However,
      periodontal diseases in HIV-seropositive and HIV-seronegative subjects are
      similar with regard to the spectrum of periodontopathic bacteria, clinical
      manifestation, natural course of the disease and response to treatment. Thus, it
      is safe to assume that candidal micro-organisms play only a minor role, if any,
      in the aetiology and pathogeneses of periodontal diseases in HIV-seropositive
      subjects.

PMID- 15974432
TI  - An evaluation of the third cervical vertebra (C3) as a growth indicator in Black
      subjects.
AB  - In orthodontics, evaluation of skeletal age and growth maturation is essential in
      diagnosis and treatment planning. The use of hand wrist radiographs perform this
      function adequately. However, it is not the only method, as the body of the third
      cervical vertebra (C3) also provides a similar information. It may be clearly
      discerned on the routine cephalogram, obviating additional radiation. This study
      sets out to present the various morphologic changes observed radiographically in
      the body of C3 at different age groups. The cephalograms of one hundred and sixty
      two patients (79 males and 83 females) were evaluated from the records at the
      Medunsa Orthodontic Department. The body of C3 was studied on each film according
      to the criteria set by Hassel & Farman. The results showed that radiographically,
      the body of C3 displayed morphological changes consistent with normal skeletal
      maturation that indicated the usefulness of this technique in clinical and
      research work. This method therefore shows promise as an alternative to hand
      wrist growth stage evaluation.

PMID- 15974433
TI  - Criteria referenced student self-assesment in restorative dentistry.
AB  - The application of criteria referenced assessment has been previously reported,
      however, criteria referenced self-assessment has not yet been studied. The
      objective of this study was to develop and use clear and explicit criteria,
      linked to a level of competency and a score, as well as a checklist, for student
      self-assessment in Restorative Dentistry. A comparison of student self-assessment
      and supervisor-assessment was also undertaken to determine the validity and
      reliability of the criteria. Six levels of competency were adapted from the
      literature and a criterion was developed for each level of competency and used
      for student self-assessment of clinical procedures in Restorative Dentistry (BChD
      IV and BChD V). Each level of competency was given a score: U = Unqualified (0),
      NBQ = Not becoming Qualified (1), BQB = Becoming Qualified as a Beginner (2), BQL
      = Becoming Qualified as a Learner (3), Q = Qualified (4), E = Exceptional (5).
      The students used the criteria on the assessment form, to assess themselves
      accordingly (U, NBQ, BQB, BQL, Q, E) and this was compared to the supervisor
      assessment using the same criteria. The results were subjected to a Spearman Rank
      Order Correlation test. The Spearman Correlation Coefficient for the BChD V group
      was 0.882 and 0.927 for the BChD IV group in the first semester and 0.923 for the
      BChD V group and 0.900 for the BChD IV group in the second semester. The results
      were highly significant (p< 0.05). There were no significant differences between
      student self-assessment and supervisor-assessment. The criteria referenced
      assessment system used to assess clinical competency in Restorative Dentistry is
      valid and reliable.

PMID- 15974434
TI  - General practitioner's radiology case 31. Atypical tuberculosis.

PMID- 15974435
TI  - Synthesis, analgesic, and anti-inflammatory activities of [6-(3,5-dimethyl-4
      chloropyrazole-1-yl)-3(2H)-pyridazinon-2-yl]acetamides.
AB  - A series of structurally diverse amide derivatives of [6-(3,5-dimethyl-4-chloro
      pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were prepared and tested for
      their in vivo analgesic and anti-inflammatory activity by using p-benzoquinone
      induced writhing test and carrageenan-induced hind paw edema model, respectively.
      The analgesic and anti-inflammatory activity of the compounds, 7c, 7d and 7k were
      found to be equipotent to aspirin (as an analgesic) and indometacin (as an anti
      inflammatory drug), respectively. The other amide derivatives generally resulted
      in lower activity on comparision with reference compounds.

PMID- 15974436
TI  - Isolation of a natural antioxidant, dehydrozingerone from Zingiber officinale and
      synthesis of its analogues for recognition of effective antioxidant and
      antityrosinase agents.
AB  - In the present study, the antioxidative and inhibitory activity of Zingiber
      officinale Rosc. rhizomes-derived materials (on mushroom tyrosinase) were
      evaluated. The bioactive components of Z. officinale rhizomes were characterized
      by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited
      potent antioxidant and tyrosinase inhibition activities. A series of substituted
      dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields
      by the reaction of appropriate benzaldehydes with acetone and the products were
      evaluated in terms of variation in the dehydrozingerone structure. The synthetic
      analogues were examined for their antioxidant and antityrosinase activities to
      probe the most potent analogue. Compound 26 inhibited Fe2+-induced lipid
      peroxidation in rat brain homogenate with an IC50 = 6.3+/-0.4 microM. In the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26,
      28, and 29 showed radical scavenging activity equal to or higher than those of
      the standard antioxidants, like alpha-tocopherol and ascorbic acid. Compound 27
      displayed superior inhibition of tyrosinase activity relative to other examined
      analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against
      oxidation of 3,4-dihydroxyphenylalanine (L-DOPA). From the present study, it was
      observed that both number and position of hydroxyl groups on aromatic ring and a
      double bond between C-3 and C-4 played a critical role in exerting the
      antioxidant and antityrosinase activity.

PMID- 15974437
TI  - Free radical scavenging and hepatoprotective constituents from the leaves of
      Juglans sinensis.
AB  - In the course of searching for hepatoprotective agents from natural products, six
      compounds were isolated from the MeOH extract of the leaves of Juglans sinensis,
      as guided by their DPPH free radical scavenging activity. The structures were
      determined as juglanoside B (1), quercetin 3-O-alpha-L-arabinofuranoside
      (avicularin, 2), quercetin 3-O-alpha-L-arabinopyranoside (guaijaverin, 3),
      quercetin 3-O-alpha-L-rhamnopyranoside (quercitrin, 4), (+)-catechin (5) and
      quercetin 3-O-beta-D-galactopyranoside (hyperin, 6). Compounds 2-6 showed
      significant DPPH free radical scavenging effects. An evaluation for the
      hepatoprotective activity of the isolated compounds on drug-induced cytotoxicity
      was conducted, and compounds 1, 2, and 5 showed protective effects against
      nitrofurantoin-induced cytotoxicity, and compound 5 also exhibited a moderate
      protective effect on amiodarone-induced cytotoxicity in Hep G2 cells.

PMID- 15974438
TI  - In vitro free radical and ONOO- scavengers from Sophora flavescens.
AB  - Activity-guided fractionation of the CH2Cl2-soluble fraction of the roots of
      Sophora flavescens furnished five 1,1-diphenyl-2-picrylhydrazyl (DPPH) free
      radical scavengers: trans-hexadecyl ferulic acid (1), cis-octadecyl ferulic acid
      (2), trans-hexadecyl sinapic acid (3), (-)-4-hydroxy-3-methoxy-(6aR,11aR)-8,9
      methylenedioxypterocarpan (4) and desmethylanhydroicaritin (8), along with nine
      known inactive compounds: (-)-maackiain (5), xanthohumol (6), formononetin (7),
      (2S)-2'-methoxykurarinone (9), (2S)-3beta,7,4'-trihydroxy-5-methoxy-8
      (gamma,gamma-dimethylallyl)-flavanone (10), (2S)-7,4'-dihydroxy-5-methoxy-8
      (gamma,gamma-dimethylallyl)-flavanone (11), umbelliferone (12), kuraridin (13),
      and trifolirhizin (14). Compounds 1-4 and 8 exhibited DPPH free radical
      scavenging effects at IC50 values of 33.01 +/- 0.20, 57.06 +/- 0.16, 39.84 +/-
      0.36, 35.83 +/- 0.47, and 18.11 +/- 0.04 microM, respectively. L-Ascorbic acid,
      when used as a positive control, exhibited an IC50 value of 7.39 +/- 0.01 microM.
      Compounds 1-4 and 8 also appeared to exert significant scavenging effects on
      authentic ONOO-, with IC50 values of 5.76 +/- 1.19, 15.06 +/- 1.64, 8.17 +/-
      4.97, 1.95 +/- 0.29, and 4.06 +/- 2.41 microM, respectively. Penicillamine (IC50
      = 2.36 +/- 0.79 microM) was used as a positive control. In addition, compounds 2,
      4, 6, 8, and 10 were isolated from this plant for the first time.

PMID- 15974439
TI  - Ergosterol peroxide from flowers of Erigeron annuus L. as an anti-atherosclerosis
      agent.
AB  - Flowers of Erigeron annuus L. were extracted with 80% aqueous MeOH, and the
      concentrated extract was partitioned with EtOAc, n-BuOH, and H2O. Repeated silica
      gel and ODS column chromatography of the EtOAc fraction led to the isolation of a
      sterol, through activity-guided fractionation, using ACAT inhibitory activity
      measurements. From the physico-chemical data, including NMR, MS, and IR, the
      chemical structure of the compound was determined to be an ergosterol peroxide
      (1), which has been isolated for the first time from this plant. This compound
      exhibited hACAT-1 and Lp-PLA2 inhibitory effects, with inhibitory values of 51.6
      +/- 0.9 and 51.7 +/- 1.2%, at a treatment concentration of 0.23 mM.

PMID- 15974440
TI  - Potentially cytotoxic triterpenoids from the root bark of Siphonodon celastrineus
      Griff.
AB  - A new oleanane-triterpene, 3beta-acetoxy-11alpha-benzoyloxy-13beta-hydroxyolean
      12-one (1), was isolated along with a known quinone-methide triterpene,
      pristimerin (2), from the root bark of Siphonodon celastrineus Griff., a Thai
      medicinal plant of the family Celastraceae. Their structures were determined
      based on spectroscopic analysis.

PMID- 15974441
TI  - Triterpenoids from the flower of Campsis grandiflora K. Schum. as human acyl-CoA:
      cholesterol acyltransferase inhibitors.
AB  - The flower of Campsis grandiflora K. Schum. was extracted with 80% aqueous MeOH,
      and the concentrated extract was partitioned with EtOAc, n-BuOH and H2O. From the
      EtOAc fraction, seven triterpenoids were isolated through the repeated silica
      gel, ODS column chromatographies and preparative HPLC. From the result of physico
      chemical data including NMR, MS and IR, the chemical structures of the compounds
      were determined as 3beta-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1),
      3beta-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3beta-hydroxyurs-12-en-28
      al (ursolic aldehyde, 3), 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (maslinic
      acid, 4), 2alpha,3beta-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5),
      3beta,23-dihydroxyurs-12-en-28-oic acid (23-hydroxyursolic acid, 6) and
      2alpha,3beta,23-trihydroxyolean-12-en-28-oic acid (arjunolic acid, 7). These
      teriterpenoids were isolated for the first time from this plant. Also, compounds
      4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the
      value of 46.2+/-1.1, 46.7+/-0.9, 41.5+/-1.3 and 60.8+/-1.1% at the concentration
      of 100 microg/mL, respectively.

PMID- 15974442
TI  - Fungicidal effect of resveratrol on human infectious fungi.
AB  - Resveratrol, a phenolic antioxidant found in grapes, has been known to mediate
      various biological activities on the human body. In the present study, we tested
      the antifungal activity of resveratrol against human pathogenic fungi before
      carrying out further studies to elucidate the antifungal mechanism(s) of
      resveratrol. Resveratrol displayed potent antifungal activity against human
      pathogenic fungi at concentration levels of 10-20 microg/mL. Furthermore, time
      kill curve exhibited fungicidal effect of resveratrol on C. albicans, but the
      compound had no hemolytic activity against human erythrocytes. The destruction of
      C. albicans cells by resveratrol was confirmed by scanning electron microscopy.
      These results suggest that resveratrol could be employed as a therapeutic agent
      to treat fungal infections of humans.

PMID- 15974443
TI  - Role of disulfide bond of arylsulfate sulfotransferase in the catalytic activity.
AB  - Bacterial arylsulfate sulfotransferase (ASST) catalyzes the transfer of sulfate
      group from a phenyl sulfate ester to a phenolic acceptor. The promoter region and
      the transcription start sites of Enterobacter amnigenus astA have been determined
      by primer extension analysis. Northern blot analysis resolved two mRNA species
      with lengths of 3.3 and 2.0 kb, which correspond to the distances between the
      transcriptional initiation sites and the two inverted repeat sequences (IRSs). By
      length, the 3.3 kb RNA could comprise the three-gene (astA with dsbA and dsbB)
      operon. ASST has three highly conserved cysteine residues. Reducing and
      nonreducing SDS-PAGE and activity staining showed that disulfide bond is needed
      for the activity of the enzyme. To identify the cysteine residues responsible for
      the disulfide bond formation, a series of Cys to Ser mutants has been constructed
      and the enzymatic activity was measured. Based on the results, we assumed that
      the first cysteine (Cys349) might be involved in disulfide bond mainly with the
      second cysteine (Cys445) and result in active conformation.

PMID- 15974444
TI  - Improvement of menopausal signs by isoflavones derived from Sophorae fructus in
      ovariectomized female rats and the antioxidant potentials in BV2 cells.
AB  - The aim of this study was to determine if the isoflavones from Sophorae fructus
      (SISO) have potential clinical benefit in hormone replacement therapy (HRT) for
      the treatment of menopausal signs, such as the levels of total cholesterol (TC),
      high density lipoprotein (HDL), low density lipoprotein (LDL) and follicle
      stimulating hormone (FSH). An additional aim was to present the potential
      antioxidant effect of SISO in a microglial cell line. For the animal model, the
      ovaries were removed from adult rats and the indicators of menopause were
      measured at the pre- and post-administration time points. Although no
      statistically significant correlation was found, SISO tended to decrease the TC
      level (p=0.15) and the FSH level (p=0.36), but to increase the HDL level
      (p=0.303). SISO (< 5 microg/mL) also exerted antioxidant activity on BV-2
      microglial cells by inhibiting lipopolysaccharide-induced nitric oxide. This
      cytoprotective effect was confirmed by trypan blue staining, which was used to
      test for cellular damage from H2O2. In conclusion, this study highlights the anti
      menopausal and antioxidant effect of SISO in an ovariectomized rat model, as well
      as in microglial cells, and provides new clinical targets for the screening of
      phytoestrogens as potential candidates for HRT in menopausal women.

PMID- 15974445
TI  - Production of cytokine and NO by RAW 264.7 macrophages and PBMC in vitro
      incubation with flavonoids.
AB  - Flavonoids, a group of low molecular weight phenylbenzopyrones, have various
      pharmacological properties including antioxidant activity, anticancer, and
      immunomodulatory effects. In the present study, lipopolysaccharide (LPS) and
      phorbol 12-myristate 13-acetate/phytohemagglutinin (PMA/PHA) were used as
      stimulants for RAW 264.7 macrophages and human peripheral blood mononuclear cell
      (hPBMC), and tumor necrosis factor (TNF)-alpha and interleukin (IL)-2 productions
      were measured. In addition, flavonoids were examined for their effects on LPS
      induced NO production in RAW 264.7 macrophages. The results showed that all
      compounds were not strongly cytotoxic at the tested concentrations on hPBMC and
      RAW 264.7 macrophages. On immunomodulatory properties, catechin, epigallocatechin
      (EGC), naringenin, and fisetin repressed NO production and TNF-alpha secretion.
      Furthermore, catechin, epigallocatechin gallate (EGCG), epicatechin (EC),
      luteolin, chrysin, quercetin, and galangin increased IL-2 secretion while EGC,
      apigenin, and fisetin inhibited the secretion. These results indicated that
      flavonoids have the capacity to modulate the immune response and have a potential
      anti-inflammatory activity. There was no obvious structure-activity relationship
      regard to the chemical composition of the flavonoids and their cell biological
      effects.

PMID- 15974446
TI  - Differential modulatory effects of cholera toxin and pertussis toxin on pain
      behavior induced by TNF-alpha, interleukin-1beta and interferon-gamma injected
      intrathecally.
AB  - The present study was designed to characterize the possible roles of spinally
      located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in
      pro-inflammatory cytokine induced pain behaviors. Intrathecal injection of tumor
      necrosis factor-alpha (TNF-alpha; 100 pg), interleukin-1beta (IL-1beta; 100 pg)
      and interferon-gamma (INF-gamma; 100 pg) showed pain behavior. Intrathecal
      pretreatment with CTX (0.05, 0.1 and 0.5 mg) attenuated pain behavior induced by
      TNF-alpha and INF-gamma administered intrathecally. But intrathecal pretreatment
      with CTX (0.05, 0.1 and 0.5 microg) did not attenuate pain behavior induced by IL
      1beta. On the other hand, intrathecal pretreatment with PTX further increased the
      pain behavior induced by TNF-alpha and IL-1beta administered intrathecally,
      especially at the dose of 0.5 microg. But intrathecal pretreatment with PTX did
      not affect pain behavior induced by INF-gamma. Our results suggest that, at the
      spinal cord level, CTX- and PTX-sensitive G-proteins appear to play important
      roles in modulating pain behavior induced by pro-inflammatory cytokines
      administered spinally. Furthermore, TNF-alpha, IL-1beta and INF-gamma
      administered spinally appear to produce pain behavior by different mechanisms.

PMID- 15974447
TI  - Extremely low frequency magnetic fields modulate bicuculline-induced-convulsion
      in rats.
AB  - The effect of extremely low frequency (ELF, 60 Hz) magnetic fields (MFs) on
      convulsions was investigated in rats. We determined the onset and duration of
      convulsions induced by bicuculline alone or by co-exposure to MFs and
      bicuculline. In addition, we measured the GABA concentrations in the rat brains
      using HPLC-ECD. MFs strengthened the convulsion induced by bicuculline (0.3, 1,
      and 3 microg, i.c.v.), with a shortening of the onset time, but lengthening of
      the duration time. Co-exposure to MFs and bicuculline decreased the GABA levels
      in the cortex, hippocampus and hypothalamus, whereas MFs alone reduced the level
      of GABA only in the hippocampus. These results suggest that the exposure to MFs
      may modulate bicuculline-induced convulsions due to GABA neurotransmissions in
      rat brains.

PMID- 15974448
TI  - Identification and quantification of steroidal saponins in Polygonatum species by
      HPLC/ESI/MS.
AB  - An HPLC/ESI/MS method has been developed to identify and quantify the spirostanol
      glycosides in the rhizomes of five Polygonatum species. The relative distribution
      of two steroidal saponins in each extract was established using the selective ion
      monitoring (SIM) mode via an electrospray ionization (ESI) source. It was found
      that there were significant differences in the amount of spirostanol glycosides
      among the Polygonatum species. The results showed that this method could be used
      to identify the steroidal saponins in the extracts and differentiate Polygonatum
      species with high sensitivity and reproducibility in a short time. Fragmentation
      patterns of the two reference compounds were also discussed with the electrospray
      ionization multi-stage tandem mass spectroscopy (ESI-MSn).

PMID- 15974449
TI  - The influence of assay error weight on gentamicin pharmacokinetics using the
      Bayesian and nonlinear least square regression analysis in appendicitis patients.
AB  - The purpose of this study was to determine the influence of weight with
      gentamicin assay error on the Bayesian and nonlinear least squares regression
      analysis in 12 Korean appendicitis patients. Gentamicin was administered
      intravenously over 0.5 h every 8 h. Three specimens were collected at 48 h after
      the first dose from all patients at the following times, just before regularly
      scheduled infusion, at 0.5 h and 2 h after the end of 0.5 h infusion. Serum
      gentamicin levels were analyzed by fluorescence polarization immunoassay
      technique with TDxFLx. The standard deviation (SD) of the assay over its working
      range had been determined at the serum gentamicin concentrations of 0, 2, 4, 8,
      12, and 16 microg/mL in quadruplicate. The polynominal equation of gentamicin
      assay error was found to be SD (microg/mL) = 0.0246 - (0.0495C) + (0.00203C2).
      There were differences in the influence of weight with gentamicin assay error on
      pharmacokinetic parameters of gentamicin using the nonlinear least squares
      regression analysis but there were no differences on the Bayesian analysis. This
      polynominal equation can be used to improve the precision of fitting of
      pharmacokinetic models to optimize the process of model simulation both for
      population and for individualized pharmacokinetic models. The result would be
      improved dosage regimens and better, safer care of patients receiving gentamicin.

PMID- 15974451
TI  - Preparation of mucoadhesive chitosan-poly(acrylic acid) microspheres by
      interpolymer complexation and solvent evaporation method II.
AB  - A mucoadhesive microsphere was prepared by an interpolymer complexation and
      solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to
      prolong the gastric residence time of the delivery system. The Fourier transform
      infrared results showed that microspheres were formed by an electrostatic
      interaction between the carboxyl groups of the PAA and the amine groups of the
      chitosan. X-ray diffraction and differential scanning calorimetry analysis showed
      that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed
      in an amorphous state. Scanning electron microscopy of the surface and the
      quantity of mucin attached to the microspheres indicated that chitosan-PAA
      microspheres had a higher affinity for mucin than those of chitosan alone. The
      swelling and dissolution of the chitosan-PAA microspheres were found to be
      dependent on the pH of the medium. The rate of enrofloxacin released from the
      chitosan-PAA microspheres was slower at higher pH; therefore, based on their
      mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used
      as a mucoadhesive oral drug delivery system.

PMID- 15974450
TI  - Effect of solubilizing and microemulsifying excipients in polyethylene glycol
      6000 solid dispersion on enhanced dissolution and bioavailability of
      ketoconazole.
AB  - Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating
      various pharmaceutical excipients or microemulsion systems, were prepared using a
      fusion method, to compare the dissolution rates and bioavailabilities in rats.
      The amorphous structure of the drug in SDs was also characterized by powder X-ray
      diffractometry (XRD) and differential scanning calorimetry (DSC). The
      ketoconazole (KT), as an antifungal agent, was selected as a model drug. The
      dissolution rate of KT increased when solubilizing excipients were incorporated
      into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined
      and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution
      rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug
      delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the
      dissolution rate by forming a microemulsion or dispersible particles within the
      aqueous medium. However, due to the limited solubilization capacity, these PEG
      based SDs showed dissolution rates, below 50% in this study, under sink
      conditions. The PEG-based SD, with no pharmaceutical excipients incorporated,
      increased the maximum plasma concentration (Cmax) and area under the plasma
      concentration curve (AUC(0-6h)) two-fold compared to the drug only. The
      bioavailability was more pronounced in the cases of solubilizing and
      microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the
      characteristic peak of the carrier matrix around 60 degrees C, without a drug
      peak, indicating that the drug had changed into an amorphous structure. The
      diffraction pattern of the pure drug showed the drug to be highly crystalline in
      nature, as indicated by numerous distinctive peaks. The lack of the numerous
      distinctive peaks of the drug in the PEG-based SDs demonstrated that a high
      concentration of the drug molecules was dissolved in the solid-state carrier
      matrix of the amorphous structure. The utilization of oils, fatty acid and
      surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance
      the dissolution and bioavailability of poorly water-soluble drugs by forming
      solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

PMID- 15974452
TI  - Reparation of controlled release spheronized beads by simple extrusion and
      modified spheronization process.
AB  - Beads loaded with the water-soluble drug, phenylpropanolamine HCl (PPA), were
      prepared using an extruder and double arm counter-rotating roller modified from a
      traditional pill machine. The mean diameter of the cylindrical rod-like extrudate
      from the ram extruder was 3 mm; that of the uncoated bead after cutting and
      spheronization by the modified double arm counter-rotating roller was 3.26-3.28
      mm. Although the surface of the beads was moderately rough and irregular, some
      exhibited hump-shaped protrusions, the sphericity was acceptable (roundness 1.15)
      and adequate for the subsequent coating process. An increase in mean diameter of
      the coated beads and improvements in friability and sphericity were observed in
      proportion to the amount of coating material applied (ethylcellulose or Eudragit
      RS 100). It was also found that the release rate of PPA from the coated beads
      could be controlled by the amount and type of coating materials applied or with
      the incorporation of Eudragit RS 100 into the core matrix. Further modifications
      to the double arm counter-rotating roller, including adjustment of the rotation
      speed and distance between the rollers, would yield smaller uncoated beads with
      improved roundness and surface roughness. In conclusion, the present method could
      be potentially applied to prepare controlled release drug delivery beads or
      pellet dosage forms.

PMID- 15974453
TI  - In vitro and in vivo studies of different liposomes containing topotecan.
AB  - Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been
      reported in attempt to improve the stability and antitumor activity of TPT.
      However, the biodistribution pattern of TPT liposome in vivo and PEG-modified
      liposome containing TPT have not been studied systemically. In this paper, the in
      vitro stability and in vivo biodistribution behavior of several liposomes
      containing TPT with different lipid compositions and PEG-modification were
      studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean
      phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated
      soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from
      liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or
      human blood plasma (HBP). The results of biodistribution studies in S180 tumor
      bearing mice showed that liposomal encapsulation increased the concentrations of
      total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip
      and H-Lip resulted in 5- and 19-fold increase in the area under the curve (AUC(0-
      >infinity)), respectively. PEG-modified H-Lip (H-PEG) showed 3.7-fold increase in
      AUC(0-->infinity) compared with H-Lip, but there was no significant increase in
      t(1/2) and AUC(0-->infinity) for PEG-modified S-Lip (S-PEG) compared with S-Lip.
      Moreover, the liposomal encapsulation changed the biodistribution behavior, and H
      Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the
      relative tumor uptake ratios were 3.4 and 4.3 compared with free drug,
      respectively. There was also a marked increase in the distribution of TPT in lung
      when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased
      the accumulation of TPT in bone marrow compared with unmodified H-Lip. All these
      results indicated that the membrane fluidity of liposome has an important effect
      on in vitro stability and in vivo biodistribution pattern of liposomes containing
      TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.

PMID- 15974454
TI  - Bidding for work?

PMID- 15974455
TI  - Doulas are helpful, but they're not nurses.

PMID- 15974456
TI  - A nursing student remembers those who guided her.

PMID- 15974457
TI  - Why do we continue to work as nurses?

PMID- 15974458
TI  - Thanks for spotlighting this little known from of breast CA.

PMID- 15974459
TI  - Inflammatory breast cancer.

PMID- 15974460
TI  - Deciding for others.

PMID- 15974462
TI  - Using technology to improve patient flow.

PMID- 15974461
TI  - Patients first!

PMID- 15974463
TI  - Your guide to OSHA regulations.

PMID- 15974464
TI  - Taking the fifth (vital sign).

PMID- 15974465
TI  - Patient information. Pain relief.

PMID- 15974466
TI  - Trauma nursing: amputation.

PMID- 15974467
TI  - What's wrong with this patient?

PMID- 15974468
TI  - A lesson in nursing.

PMID- 15974469
TI  - Vent injury: how to avoid it.

PMID- 15974470
TI  - Back to school? Nurses say: You bet!

PMID- 15974471
TI  - Nursing schools are failing us.

PMID- 15974472
TI  - A fMRI study of age-related differential cortical patterns during cued motor
      movement.
AB  - Healthy adults of three age groups (young, middle-age and older) were cued by a
      multimedia projector to perform a series of simple (making a fist,
      opening/closing of the mouth) and complex (opposition of index finger and thumb,
      chewing gum) motor tasks while being scanned by functional magnetic resonance
      imaging. Our results showed that in unilateral hand movements, the premotor/motor
      cortex in the contralateral hemisphere was most strongly activated. Supplementary
      motor cortex involvement was usually present in the young and not in the old,
      except in precision movement when supplementary motor cortex was also involved in
      the old. For movements of the face (chewing, opening and closing of mouth), the
      prefrontal cortex was activated in the old age group but finger and hand
      movements never activated the prefrontal cortex in any age. Furthermore, areas
      like insula and cingulate gyrus might be activated in motor tasks. We conclude
      that different motor activities triggered diverse activation patterns which
      differed in different age groups.

PMID- 15974473
TI  - Auditory detection of motion velocity in humans: a magnetoencephalographic study.
AB  - To investigate the cerebral mechanisms of auditory detection of motion velocity
      in the human brain, neuromagnetic fields elicited by six moving sounds and one
      stationary sound were investigated with a whole-cortex magnetoencephalography
      (MEG) system. The stationary sound evoked only one clear response at a latency of
      109+/-6 ms (first response, or M100), but the six moving sounds evoked two clear
      responses: an earlier response at a latency of 116+/-7 ms (M100) and a later
      response at a latency ranging from 180 to 760 ms (magnetic motion response, or
      MM). The latency and amplitude of the MM were inversely related to the velocity
      of the moving sounds (p<0.02). The magnetic source of MM was related to the
      velocity of the moving sounds (p<0.05). A dynamic neuromagnetic response, MM, was
      elicited by the moving sounds, which likely encoded the neural processing of
      auditory detection of motion velocity. A specific neural network that processes
      the motion velocity in the human brain probably includes the bilateral superior
      temporal cortices and the brainstem. The left posterior and lateral part of the
      auditory cortex may play a pivotal role in the auditory detection of motion
      velocity.

PMID- 15974474
TI  - Integrated study of topographical functional maps based on an auditory
      comprehension paradigm using an eigensystem study and spectrum analysis.
AB  - This study integrates a spectral analysis of key frequency bands (Alpha, Beta,
      Delta, and Theta) with an eigensystem-based study in order to validate brain
      functional mappings associated with the characterization effects of an
      Auditory/Comprehension paradigm. This numerical characterization supported by
      topographic functional maps brings added insight in the involvement of the
      Wernicke and Broca's brain areas to language comprehension. A thorough
      examination of EEG recordings through the eigensystem reveals that eigenvectors
      associated with the largest eigenvalues produce an interesting activity pattern
      located in the frontal area of the brain directly attributable to those
      characteristic behaviors found in the Alpha, Beta, Delta, and Theta frequency
      bands. An evaluation of spectral arrays is performed using topographic maps of
      the induced brain activities during both listening and answering phases. This
      evaluation is then augmented with quantifying measures using the eigensystem
      study while results are validated through integration of EEG activity and
      eigensystem modalities. Such a representation can provide insightful information
      on how different patients react during an auditory and response phases, and in
      the ability to detect the presence of potential neurological disorders by
      assessing similar/dissimilar behaviors with respects to all former patients
      already included in the database. The algorithm as developed in this study could
      be extended in its application to other brain functional mapping tasks given its
      simple but effective practical mathematical foundation.

PMID- 15974475
TI  - Age distribution of MEG spontaneous theta activity in healthy subjects.
AB  - This study investigates the possible relevance of distribution and age variation
      of spontaneous theta activity (4-8 Hz) in normal subjects using
      magnetoencephalography (MEG) recordings. Spontaneous theta was recorded with a
      151-channel MEG in healthy subjects; moreover, in a group of 10 subjects,
      simultaneous MEG-EEG was recorded in order to compare the two methods. Theta was
      divided in two sub-bands: T(A) (4-6 Hz) and T(B) (6-8 Hz). The pre-processed data
      were transformed into the frequency domain by Fast Fourier Transform (FFT)-based
      software by subdividing the data in epochs of 5 sec, on which FFT amplitudes are
      computed. Moreover, on all trials a simple model of a single electric current
      embedded in a spherically symmetric conductor was fitted automatically to the
      magnetic fields and projected onto an averaged MRI. The results obtained show
      that FFT-based theta power spectrum was distributed in adults with the highest
      power over the posterior parietal and occipital areas with T(B) dominance. The
      dipole analysis resulted in a mid-sagittal distribution, though the youngest
      group displayed theta dipoles fitting more posteriorly respect to the adults and
      the elderly. These results suggest that spontaneous theta activity is a diffuse
      and pervasive rhythm which shows some different topographical distribution among
      the age groups. Whether the prevalent posterior distribution of theta is the
      expression of distinct networks or the outcome of complex dynamics are questions
      of possible relevance in the organization of higher order processes.

PMID- 15974476
TI  - Protective effect of hawthorn fruit on murine experimental colitis.
AB  - The pathogenic mechanism and effective treatment of inflammatory bowel disease
      (IBD) are still unknown. In the present study, we examined the protective effect
      of hawthorn fruit (Crataegifructus) on two murine colitis models: dextran sulfate
      sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Mice that
      developed acute colitis showed signs of diarrhea, gross rectal bleeding and
      weight loss within 10 days. However, hawthorn fruit (2 g/kg body weight) restored
      the body weight and colon length and increased hemoglobin count in these animals.
      Hawthorn fruit not only decreased signs of inflammation such as infiltration by
      polymorphonuclear leukocytes and multiple erosive lesions, but also showed
      improvement of leukotriene B4 (LTB4), a biochemical parameter of inflammation
      mass. TNBS colitis mice had significantly lower rates of survival than normal
      control animals; however, treatment with hawthorn fruit significantly improved
      survival in TNBS colitis mice. The results suggest that hawthorn fruit and the
      Kampo formula that contains this ingredient may have potential therapeutic
      utility in patients with IBD.

PMID- 15974477
TI  - Protective effect of jakyak-gamcho-tang extract and its constituents against t
      BHP-induced oxidative damage in HT22 cells.
AB  - The present study investigated whether Jakyak-Gamcho-Tang (JGT, Shaoyao-Gancao
      tang) and its constituents have the protective effect against tert-butyl
      hydroperoxide (t-BHP)-induced cytotoxicity on hippocampal HT22 cell line. JGT
      consists of two medicinal herbs, Paeoniae Radix (PR) and Glycyrrhizae Radix (GR).
      In contrast to treating with t-BHP alone, pre-treatment of HT22 cells with JGT,
      PR and GR (50-400 microg/ml) for 3 hours significantly increased the cell
      viability in a concentration-dependent manner. In addition, JGT, PR and GR
      exhibited the scavenging activity in both 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical and superoxide anion assays. Among the tested extracts, PR showed the
      most potent protective and antioxidative activities. These results suggest that
      PR acts as an antioxidant and this property may contribute to the neuroprotective
      activity of JGT extract.

PMID- 15974478
TI  - Susceptibilities of Mycoplasma hominis to herbs.
AB  - To determine the susceptibilities of Mycoplasma homonis (M. hominis) to Chinese
      medicinal herbs in vitro, 30 clinical strains of M. hominis were isolated and
      identified from the clinical specimen. The susceptibilities of M. hominis to 19
      herbs were determined by serial dilution methods in vitro. The results showed
      that M. hominis was susceptible to Radix Isatidis, Radix Angelicae Dahuricae,
      Cortex Phellodendri, Radix et Rhizoma Rhei, Fructus Kochiae and Herba
      Houttuyniae. These findings laid a foundation in treating M. hominis infection
      with Chinese herbs.

PMID- 15974479
TI  - The antimicrobial activities of Psidium guajava and Juglans regia leaf extracts
      to acne-developing organisms.
AB  - This study aims to present the in vitro inhibitory effect of Psidium guajava and
      Juglans regia leaf extracts on the main developer of acne lesions,
      Propionibacterium acnes (P. acnes), and other organisms that are isolated from
      acne lesions. Thirty-eight subjects (males and females) who had various types of
      acne were enrolled in the study. The contents of the acne lesions were cultured
      and the frequency of P. acnes (alone and with Staphylococci spp.) was 47%,
      whereas the frequencies for Staphylococcus aureus and Staphylococcus epidermidis
      were 13% and 24%, respectively. The antimicrobial activities of Psidium guajava
      and Juglans regia leaf extracts, determined by disk diffusion method (zone of
      inhibition), were compared to tea tree oil (TTO), doxycycline and clindamycin
      antibiotics. The zones of inhibition due to the Psidium guajava and Juglans regia
      leaf extracts ranged from 15.8-17.6 mm against P. acnes, 11.3-15.7 mm against S.
      aureus and 12.9-15.5 mm against S. epidermidis, respectively. These zones of
      inhibition were significantly higher than those of TTO and equivalent in case of
      Staphylococci spp., but less in case of P. acnes, to those obtained from
      doxycycline or clindamycin. It can be concluded that Psidium guajava and Juglans
      regia leaf extracts may be beneficial in treating acne especially when they are
      known to have anti-inflammatory activities.

PMID- 15974481
TI  - Effect of Eucommia ulmoides on systolic blood pressure in the spontaneous
      hypertensive rat.
AB  - Experiments were conducted to establish the safety and efficacy of Eucommia
      ulmoides (Du-Zhong) extract in the treatment of hypertension. Pilot experiments
      using rats demonstrated that E. ulmoides extract was safe to the saturation
      limits of the compound. The maximum tolerated dose (MTD) was 1200 mg/kg when
      administered by gastric gavage at a concentration of 1200 mg/ml. Also, rats given
      200 mg/kg, 600 mg/kg or 1200 mg/kg doses of E. ulmoides extract daily for 28 days
      demonstrated no evidence of acute toxicity as determined by clinical appearance,
      histopathology and serum chemistry evaluation. Lastly, spontaneous hypertensive
      rats (SHRs) were administered E. ulmoides extract daily for 22 days. Systolic
      blood pressure (BP) was measured on treatment days 1, 8, 15 and 22 at 0, 1, 2 and
      3 hours post-treatment. Beginning on day 8, E. ulmoides extract administered at
      the mid or high dosages lowered BP in male, but not female, rats. BP declined at
      a rate of approximately 10 mmHg per hour. The mid dosage of 600 mg/kg was found
      to be the minimum effective dose. In conclusion, E. ulmoides extract was non
      toxic and effective in reducing systolic BP in the SHR.

PMID- 15974480
TI  - The anti-depressant effect of Nelumbinis semen on rats under chronic mild stress
      induced depression-like symptoms.
AB  - Nelumbinis Semen is a well-known traditional herbal medicine frequently used in
      treatment of depression in many Asian countries. In this study, its anti
      depression effects in rats were investigated by comparing the test results of
      those treated with Nelumbinis Semen to those treated with other herbal anti
      depressants, including Rehmanniae Radix Preparat, Corni Fructus, Lycii Fructus,
      Pinelliae Rhizoma and Hypericum Perforatum. In order to induce depression-like
      symptoms, the animals were placed under chronic mild stress in the form of
      overnight illumination for 2 consecutive days. They were treated with the
      respective herbal extract and forced swimming tests were conducted afterwards.
      The anti-depression effects of each extract were then evaluated based on a
      measured index, which consisted of struggling time, first latency and first rest
      duration. These test results show that Nelumbinis Semen provides greater anti
      depression effects than the other herbal extracts. Specifically, only the rats
      treated with Nelumbinis Semen showed significant increases in struggling time
      (43.9%, p < 0.005, p = 0.0037) and in first latency time (90.2%, p < 0.05, p =
      0.0116). However, the first rest duration for Nelumbinis Semen treated rats was
      not significantly different from the other rats. It appears that Nelumbinis Semen
      provides even greater anti-depression effects than Hypericum Perforatum (commonly
      referred to as St. John's Wort, perhaps the most widely used natural
      antidepressant today). The anti-depression effects of Nelumbinis Semen might be
      due to the modulation of the amount of neurotransmitters involved in depression.

PMID- 15974482
TI  - Immune activation and radioprotection by propolis.
AB  - In this study, we focused on immune stimulation by Propolis, and examined changes
      in the effect of irradiation after Propolis administration. We also examined the
      radioprotective effect of Propolis by observing its effect on the immune system.
      The effect of immune activation by Propolis was investigated by measuring the
      total immunoglobulin (Ig) G and IgM. The radioprotective effect of immune
      activation by Propolis was investigated by measuring the T-lymphocyte subsets in
      the peripheral blood of mice following whole body irradiation. Compared with the
      control group, the IgG was significantly reduced in the Propolis group,
      indicating that Propolis suppressed IgG production. ELISA revealed that the
      amount of IgM in mouse serum was significantly higher in the Propolis group as
      compared with the control group, indicating that Propolis increased IgM
      production. The number of CD4-positive cells was increased only in the Propolis
      group. Likewise, the number of CD4-positive cells increased by 81% in the
      Propolis with irradiation group compared with the irradiation group alone.
      Compared with the control group, the Propolis group increased CD8-positive cells.
      Compared with the irradiation alone group, CD8-positive cells were decreased by
      Propolis with irradiation group. Propolis activated macrophages to stimulate
      interferon (IFN)-gamma production in association with the secondary activation of
      T-lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines
      released from macrophages in mouse peripheral blood after Propolis administration
      activated helper T-cells to proliferate. In addition, activated macrophages in
      association with the secondary T-lymphocyte activation increased IFN-gamma
      production and stimulated proliferation of cytotoxic T-cells and suppressor T
      cells, indicating the activation of cell-mediated immune responses.

PMID- 15974483
TI  - Efficacy and safety of chunghyul-dan (qingwie-dan) in patients with
      hypercholesterolemia.
AB  - Chunghyul-dan has inhibitory effects on HMG-CoA reductase and pancreatic lipase.
      We investigated whether Chunghyul-dan has therapeutic effects on humans with
      hypercholesterolemia. This study was a case-control, open-labeled clinical study.
      Subjects were treated with Chunghyul-dan (600 mg/day) or Atorvastatin (10 mg/day)
      for 8 weeks. Serum lipids were checked at baseline after 4 and 8 weeks of
      medication. While, Chunghyul-dan showed significant lipid-lowering effects, it
      was less effective than Atorvastatin. In comparison with the histological
      controls, Chunghyul-dan's effects were superior to placebo. On safety assessment,
      there was no adverse effect with the use of Chunghyul-dan in hepatic or renal
      toxicity. In conclusion, we suggest that Chunghyul-dan is a useful herbal
      medicine for hypercholesterolemia.

PMID- 15974485
TI  - Comparing the effects of estrogen and an herbal medicine on peripheral blood flow
      in post-menopausal women with hot flashes: hormone replacement therapy and gui
      zhi-fu-ling-wan, a Kampo medicine.
AB  - We investigated the association between blood flow in the extremities and hot
      flashes, and compared change in blood flow following hormone replacement therapy
      (HRT) and Gui-zhi-fu-ling-wan (Keishi-bukuryo-gan), a herbal therapy in post
      menopausal women with hot flashes. Three hundred and fifty-two post-menopausal
      women aged 46-58 years (mean: 53.4 +/- 3.6 years) with climacteric complaints
      participated in the study. One hundred and thirty-one patients with hot flashes
      were treated with HRT (64 cases) or herbal therapy (67 cases). Blood flow was
      measured with laser doppler fluxmetry under the jaw, in the middle finger and in
      the third toe. Post-menopausal women with hot flashes (129 cases) showed
      significantly higher blood flow under the jaw (13.6 +/- 4.13) than women without
      hot flashes (166 cases) (5.48 +/- 0.84) (p < 0.0001). Blood flow at this site
      decreased significantly with either therapy (p < 0.0001). On the other hand, the
      administration of Gui-zhi-fu-lingwan significantly increased (p = 0.002) the
      blood flow in the lower extremities, whereas HRT decreased the blood flow. Thus,
      we have demonstrated that Gui-zhi-fu-ling-wan did not affect the activity of
      vasodilator neuropeptides on sensory neurons of systemic peripheral vessels
      uniformly. Therefore, Gui-zhi-fu-ling-wan, rather than HRT, is suggested as an
      appropriate therapy for treatment of hot flashes in the face and upper body with
      concomitant coldness in the lower body, which is one of the symptoms of
      menopause.

PMID- 15974484
TI  - Clinical and psychological assessment on xinwei decoction for treating functional
      dyspepsia accompanied with depression and anxiety.
AB  - The purpose of this study is to explore the psychological efficacy of Xinwei
      Decoction, a traditional Chinese herbal medicine, to treat functional dyspepsia
      (FD) accompanied with depression and anxiety. Seventy-three subjects, divided
      into three groups, had been given herbal medicine (Xinwei Decoction), prokinetic
      agent (Domperidone) and placebo, respectively for 8 weeks. Before and after
      treatment, all subjects were examined with FD symptom scale, Hamilton Depression
      Scale (HAMD) and Hamilton Anxiety Scale (HAMA). As a result, the total scores of
      the three groups in FD symptom scale, HAMD and HAMA after treatment decreased in
      different levels, with the decrease in the herbal group more significant than the
      other two groups (p < 0.01), indicating the efficacy of the herbal medicine. The
      total effective rates of the herbal, Domperidone and placebo groups were 90%, 67%
      and 31%, respectively, which indicated significant effect differences between
      Xinwei Decoction and Domperidone (p < 0.05) and between Xinwei Decoction and
      placebo (p < 0.01), showing that the efficacy of herbal therapy was superior to
      that of the other two therapies. Furthermore, there was no one in the Domperidone
      and placebo groups being cured of depression and anxiety, while the curing rate
      in the herbal group was about 70%, indicating the efficacy of herbal medicine in
      comparison to that of Domperidone and placebo for anti-depression and anti
      anxiety. The result demonstrated that Xinwei Decoction could not only alleviate
      FD symptoms but also relieve depression and anxiety.

PMID- 15974486
TI  - A survey of attitudes to traditional chinese medicine among Chinese medical
      students.
AB  - We studied the attitudes and personal experiences with traditional Chinese
      Medicine (TCM) use in Chinese medical students. Medical students at the Chinese
      University of Hong Kong were asked 13 questions according to an anonymous survey.
      Six hundred and eleven of 780 medical students (47% males, 52% females) returned
      the questionnaire; 199 (33%) of the participants used TCM at least once in the
      past year, and 85% had ever tried various TCM. The attitude was positive in 41%,
      neutral in 52% and negative in only 6%. The majority (70%) reported no change in
      attitudes towards TCM after studying Western medicine (WM). Of the 199
      participants who had used TCM in the past year, upper respiratory infections were
      the most common circumstance leading to TCM usage, with 31% immediately using TCM
      without any TCM practitioner consultation. The most common modality of TCM used
      by 85% of participants was herbal decoction, and nearly one-quarter had used over
      the-counter Chinese medicine. Although 78% reported they knew of the TCM
      practitioner or treatment from family members or friends, 14% stated they
      randomly selected the practitioner. "Effectiveness of TCM," "fewer side effects
      than WM," "illness not completely treated by WM" and "recommendation from
      family/friends" were common beliefs held by participants for TCM usage. Forty
      five percent reported that they had not been told of any side effects of TCM. Pre
      clinical students had more positive attitudes towards TCM and consulted TCM
      practitioners more often in the past 12 months (OR 9.1, CI 3.16-28.18; p < 0.001)
      compared to students in clinical years, who tended to become more negative
      towards TCM after studying WM. TCM usage is common among medical students in Hong
      Kong. It is important to note that nearly half of the students were not aware of
      any possible side effects from TCM. Students appear to become more negative
      towards TCM after studying WM.

PMID- 15974487
TI  - A computer method for validating traditional Chinese medicine herbal
      prescriptions.
AB  - Traditional Chinese medicine (TCM) has been widely practiced and is considered as
      an alternative to conventional medicine. TCM herbal prescriptions contain a
      mixture of herbs that collectively exert therapeutic actions and modulating
      effects. Traditionally defined herbal properties, related to the pharmacodynamic,
      pharmacokinetic and toxicological, as well as physicochemical properties of their
      principal ingredients, have been used as the basis for formulating TCM multi-herb
      prescriptions. These properties are used in this work to develop a computer
      program for predicting whether a multi-herb recipe is a valid TCM prescription.
      This program is based on a statistical learning method, support vector machine
      (SVM), and it is trained by using 575 well-known TCM prescriptions and 1961 non
      TCM recipes generated by random combination of TCM herbs. Testing results by
      using 72 well-known TCM prescriptions and 5039 non-TCM recipes showed that 73.6%
      of the TCM prescriptions and 99.9% of non-TCM recipes are correctly classified by
      this system. A further test by using 48 TCM prescriptions published in recent
      years found that 68.7% of these are correctly classified. These accuracies are
      comparable to those of SVM classification of other biological systems. Our study
      indicates the potential of SVM for facilitating the analysis of TCM
      prescriptions.

PMID- 15974488
TI  - The use of preventive strategies for bone loss.
AB  - Osteoporosis is a worldwide problem that is increasing significantly as the
      global population both increases and ages. While osteoporosis has been
      extensively studied in recent years, the utilization of traditional Chinese
      medicine (TCM) for the diagnosis, prevention and treatment of this condition has
      seldom been examined. This paper examines the theories and the literature that
      relate to diagnosis, prevention and treatment of bone loss at the time of
      menopause according to the principles of TCM. It also considers practical
      developments in these areas as illustrated by the authors' research findings in
      recent studies. TCM diagnosis attributes a number of different underlying
      patterns to menopausal bone loss. A very common pattern in this situation is a
      Kidney qi and yin deficiency pattern. TCM analysis can be used as an early
      determinant of those persons who are potentially at risk of bone loss.
      Acupuncture, herbal medicine and Tai Ji exercise can then be applied to prevent
      and treat osteoporosis. These treatments can be effective, if they are applied
      correctly. The therapies may also be used in the treatment and prevention of
      osteoporosis, as well as the general maintenance of women's health during
      menopause.

PMID- 15974489
TI  - Atropine-induced HRV alteration is not amended by electroacupuncture on Zusanli.
AB  - Acupuncture is known to influence autonomic nervous activity. Acupuncture on
      Zusanli points has been shown to enhance the regularity of gastric myoelectrical
      activity and accelerate gastric emptying, partly through the vagal pathway, in
      dogs. The aim of this study was to evaluate whether atropine-induced autonomic
      nervous alteration, measured by heart rate variability (HRV), could be amended by
      electroacupuncture on Zusanli points. HRV measurements were recorded in 15
      healthy volunteers before, during and after electroacupuncture. Each subject was
      studied for three sessions in a randomized sequence, which included
      electroacupuncture on the Zusanli (St 36) points with or without premedication of
      atropine and placebo stimulation on a non-acupoint. The analysis of low frequency
      (LF), high frequency (HF) and LF/HF ratios were compared between different
      sessions. Serum levels of gastrin, motilin and pancreatic polypeptide (PP) levels
      were also measured. There was an increase in the LF/HF ratio (indicating
      increased sympathetic activity) during the post-acupuncture period with 2 Hz of
      electrical stimulation on the Zusanli acupoints. When IV atropine was used
      immediately before the electroacupuncture, there was a decrease in the LF power
      and HF power during the acupuncture and post-acupuncture periods. In addition,
      there was a significant increase in the LF/HF ratio during the acupuncture and
      post-acupuncture periods. There was a significant decrease in serum PP in the
      post-acupuncture period after premedication with IV atropine. In conclusion,
      atropine-induced HRV change might be mediated via the vagal pathway. However,
      atropine-induced HRV alteration is not amended by electroacupuncture on Zusanli
      points.

PMID- 15974490
TI  - A medical qigong methodology for early intervention in autism spectrum disorder:
      a case series.
AB  - A medical Qigong protocol was applied to a group of eight autistic children under
      the age of six. The children received medical Qigong massage twice weekly from
      the physician and daily Qigong massage from the parents for a five-week period,
      followed by daily parent massage for an additional four weeks. Standardized tests
      showed a decrease in autistic behaviors and increase in language development in
      all the children, as well as improvement in motor skills, sensory function and
      general health.

PMID- 15974491
TI  - Deqi sensation between the acupuncture-experienced and the naive: a Korean study
      II.
AB  - Previous experience of acupuncture is believed to affect people's expectation of
      future treatments. Therefore, subjects who have had acupuncture are generally
      excluded from sham-controlled acupuncture clinical trials. However, this
      assumption has not been proven, but just accepted because of the lack of evidence
      to the contrary. To investigate the difference in frequency and intensity of
      acupuncture sensation between subjects who have had acupuncture and those who
      have not, 36 acupuncture-experienced subjects were invited to take part in the
      study. After informed consent was obtained, participants were asked to complete
      the acupuncture sensation scale (ASS) according to what they expected needling to
      feel like. The needling was done at the left Hegu (LI 4) point and consisted of
      insertion, stimulation for 30 seconds and removal. After needling, the subjects
      were asked to complete the same ASS according to what they actually experienced.
      Adverse events were monitored. The frequency of each sensation expected and
      experienced, as well as acupuncture sensation scores were compared. More than 60%
      of the subjects expected to feel sensations of penetrating (87.6% to 100%),
      aching (71.2% to 95.5%), tingling (87.6% to 100%), pricking (79.7% to 99.2%) and
      throbbing (64.2% to 91.4%). In fact, the subjects experienced sharp (60.9% to
      89.1%), intense (60.9% to 89.1%), radiating (71.2% to 95.5%) and heavy (74.8% to
      97.4%) sensations just as much. The subjects expected more hurting (p = 0.001),
      tingling (p < 0.001), pricking (p = 0.010), stinging (p = 0.012), burning (p =
      0.001) and pulsing (p = 0.009) than they experienced, while more heaviness (p =
      0.011) was experienced than expected. The same outcome measures were also
      compared between experienced and naive groups. Apart from the fact that the
      acupuncture-experienced participants expected to feel pricking (p = 0.030) and
      stinging (p = 0.002), and experienced hurting (p = 0.022) and stinging (p =
      0.028) significantly less than those who had not had acupuncture before, there
      was no significant difference between first time and experienced subjects. The
      results indicate that previous experience does not affect the people's
      expectation and does not hinder people from experiencing Deqi. In addition, a
      constellation of Deqi-related acupuncture-specific sensations is more than just a
      general pain intensity dimension, which requires a biochemical and physiological
      exploration.

PMID- 15974492
TI  - How Galen's "sixteen books" came to China in the tenth century AD.
AB  - Ibn an-Nadim, the famous 10th century bookseller and bibliographer of Baghdad and
      author of the "Fihrist" (Catalogue), tells the story of an unnamed Chinese
      student who found in the library of the famous physician and philosopher ar-Razi
      the so-called "Sixteen Books," i.e. the Arabic summary of the most influential
      books written by Galen, and translated them into Chinese. We do not know if this
      Chinese translation was safely transported to China.

PMID- 15974493
TI  - Applying the readiness to change model to implementation of family intervention
      for serious mental illness.
AB  - Family intervention for serious mental illness is known to be highly efficacious
      in reducing patient relapse, improving social functioning, enhancing caregivers'
      knowledge of mental illness, and ultimately reducing overall costs of care.
      However, very few families receive services. The reasons for this gap between
      empirical findings and program implementation are complex and not yet fully
      understood. Prochaska and DiClemente's Readiness to Change Model provides a
      helpful structure for understanding key issues for the four relevant stakeholders
      (patients, family members, clinicians and administrators). Staging each
      stakeholder group and applying corresponding "interventions" (processes of
      change) are useful in a site's implementation of family services.

PMID- 15974494
TI  - Measuring personal loss among adults coping with serious mental illness.
AB  - Psychometric properties of a brief self-report measure of personal loss for
      adults coping with psychiatric disability are examined. The Personal Loss from
      Mental Illness Scale (PLMI) is a 20-item measure that assesses overall
      perceptions and four interrelated aspects of personal loss from mental illness.
      Using a sample of 158 adults with serious mental illness, the PLMI was found to
      have a meaningful factor structure, good internal consistency and high test
      retest reliability. Construct validity is evidenced by positive correlations
      between personal loss scores, number of psychiatric hospitalizations, self
      reports of loneliness, psychological symptoms, and problems with alcohol. PLMI
      scores were unrelated to scores on a personal growth measure and negatively
      correlated with scores on a positive well-being scale. Implications of the PLMI
      for research on coping, adaptation and recovery from serious mental illness are
      discussed.

PMID- 15974495
TI  - Implementing recovery oriented evidence based programs: identifying the critical
      dimensions.
AB  - In the decades of the 1990s many mental health programs and the systems that fund
      these programs have identified themselves as recovery-oriented. A program that is
      grounded in a vision of recovery is based on the notion that a majority of people
      can grow beyond the catastrophe of a severe mental illness and lead a meaningful
      life in their own community. First person accounts of recovery and empirical
      research have led to a developing consensus about the service delivery values
      underlying recovery. The emphasis on recovery-oriented programming has been
      concurrent with a focus in the field on evidence-based practices. We propose that
      evidence based practices be implemented in a manner that is recovery compatible.
      Program dimensions for evidence based practice, such as program mission,
      policies, procedures, record keeping and staffing should be consistent with
      recovery values in order for a program to be considered to be recovery-oriented.
      This article describes the critical dimensions of such value based practice,
      regardless of the service the recovery oriented mental health programs provide
      (e.g., treatment, case management, rehabilitation). The aim of this first attempt
      at conceptualizing recovery-oriented mental health programs is to both provide
      direction to those involved in program implementation of evidence based mental
      health practices, as well as providing a stimulus for further discussion in the
      field.

PMID- 15974496
TI  - Characteristics of individuals with severe mental illness who use emergency
      services.
AB  - Emergency services are both a safety net and a locus for acute treatment. While
      the population with severe, persistent mental illness uses emergency services at
      a high rate, few studies have systematically examined the causes of this service
      use. This study examines a random sample of 179 people who were high uti- lizers
      of services from the Los Angeles County Department of Mental Health. Interviews
      were conducted and 5 years of service use data were studied. Greater use of
      emergency services was associated with male gender, minority race, severe
      illness, homelessness, and less family support. Efforts to reduce emergency
      services need to improve access to appropriate community services, particularly
      for people who are homeless or lack family support.

PMID- 15974497
TI  - The poor general health of the severely mentally ill: impact of schizophrenic
      diagnosis.
AB  - This study focused on poor health among the severely mentally ill and additional
      risks associated with schizophrenia. Records of 781 clients in short-term
      residential treatment programs provided data. The schizophrenic subgroup was
      compared to others in bivariate analyses, with significant findings included in
      logistic regression. Those with schizophrenia were more likely to be male,
      unemployed, and insured by MediCal/Medicare. Most health problems occurred at
      similar rates across diagnoses, reflecting common environmental risk factors.
      Those with schizophrenia had less substance abuse and fewer liver conditions, but
      more diabetes and chronic respiratory problems. Implications for providers and
      for research are discussed.

PMID- 15974498
TI  - Social workers' experiences of the world trade center disaster: stressors and
      their relationship to symptom types.
AB  - The study describes New York area social workers' experiences of nine different
      stressors on 9/11. It also examines their reports of working with clients within
      the 6 months after 9/11. These variables are then analyzed for their relationship
      with symptomology 6 months after 9/11. Proximity to the WTC on 9/11, knowing
      someone who was a primary victim, and talking with clients about events related
      to 9/11 were all related to symptom levels; however, these experiences
      differentially impacted levels of depressive, anxiety, and somatic symptoms. Sex
      and race differences were found among the variables.

PMID- 15974500
TI  - Psychiatric disposition of patients brought in by crisis intervention team police
      officers.
AB  - BACKGROUND: As part of an effort to improve police interactions with mentally ill
      citizens, and improve mental health care delivery to subjects in acute distress,
      the University of Louisville, in conjunction with the Louisville Metro Police,
      established the crisis intervention team (CIT). CIT is composed of uniformed
      officers who receive extensive training in crisis intervention and psychiatric
      issues and who are preferentially called to investigate police calls that may
      involve a mentally ill individual. METHODS: In an effort to determine the
      characteristics of the individuals brought to the emergency psychiatric service
      (EPS) by CIT officers, a comparative (CIT vs. mental inquest warrant [MIW, a
      citizen-initiated court order to bring someone for psychiatric evaluation because
      of concerns regarding dangerousness] vs non-CIT/non-MIW), descriptive evaluation
      was performed. RESULTS: With the exception of a higher rate of schizophrenic
      subjects brought in by CIT (43.0% vs. 22.1%, non-CIT, P = .002), the
      demographics, diagnosis, and disposition of CIT-referred subjects were not
      different in any way from non-CIT patients. Subjects referred on MIWs were more
      likely to be admitted to a psychiatric hospital than non-MIW patients (71.6% vs.
      34.8%, P < .0001), but CIT-referred hospitalization rates were not different from
      hospitalization rates of self-referred subjects (20.7% vs. 33.3%, ns).
      CONCLUSIONS: CIT officers appear to do a good job at identifying patients in need
      of psychiatric care.

PMID- 15974501
TI  - Trend analysis of the sex ratio at birth in the United States.
AB  - OBJECTIVES: This report presents total sex ratios at birth from 1940 to 2002, for
      race starting in 1970, for Hispanic origin groups starting in 1989, for live
      birth order starting in 1943, and for age of mother for the full time period.
      METHODS: Descriptive tabulations of sex ratios using the birth data set are
      presented and interpreted. Joinpoint regression analysis is used to detect
      changes in the sex ratio over time. RESULTS: The United States sex ratio at birth
      had three significant transitions from 1940 to 2002 (1942, 1959, and 1971). White
      women were the only race group to have any significant changes in the sex ratio
      between 1970 and 2002 (1972, 1976, and 1988). Between 1940 and 2002 significant
      transitions in sex ratios occurred to women aged 20-24 (1942, 1966, 1974, and
      1987); 25-29 (1961 and 1968); 35-39 (1965 and 1976); and 40-44 years (1967).

PMID- 15974502
TI  - Determining positivity of alcohol abuse by Taguchi methods.
AB  - PURPOSE: Aims to establish the critical score and screening accuracy of the CAGE
      Questionnaire in three treatment settings--primary health care, walk-in (triage)
      clinic and the emergency room. DESIGN/METHODOLOGY/APPROACH: Taguchi methods are
      applied to three screens of the CAGE questionnaire. FINDINGS: Analysis of the
      sensitivity and specificity data of three CAGE screens by leveling factor (p'),
      signal-to-noise ratios (S/N, SS/N) and their dependent relation resulted in
      critical CAGE scores of 1, 1 and 2; and high screening accuracy levels of 98.44,
      97.20 and 94.92 percent, respectively. The illustrated method yielded excellent
      (> or = 95 percent) screening accuracy values for primary health care, emergency
      room and walk-in clinic patients. ORIGINALITY/VALUE: To reduce misclassification
      rates of alcohol abuse, screening systems should concentrate first on developing
      ways to standardize protocols. Further work is needed to establish high screening
      accuracy in other clinical settings, and particularly in those at risk of alcohol
      abuse in the general population.

PMID- 15974499
TI  - Psychosocial treatment of children in foster care: a review.
AB  - A substantial number of children in foster care exhibit psychiatric difficulties.
      Recent epidemiological and historical trends in foster care, clinical findings
      about the adjustment of children in foster care and adult outcomes are reviewed,
      followed by a description of current approaches to treatment and extant empirical
      support. Available interventions for these children can be categorized as either
      symptom-focused or systemic, with empirical support for specific methods ranging
      from scant to substantial. Even with treatment, behavioral and emotional problems
      often persist into adulthood resulting in poor functional outcomes. We suggest
      that self-regulation may be an important mediating factor in the appearance of
      emotional and behavioral disturbance in these children.

PMID- 15974503
TI  - Patient-centred quality improvement audit.
AB  - PURPOSE: This article aims to describe the research process, and the development
      of the instrument now employed in auditing patients' perceptions of quality
      improvement in a community health care trust in a coastal town in Essex, England.
      DESIGN/METHODOLOGY/APPROACH: The new instrument is currently being implemented
      and the findings thus far are described. FINDINGS: The instrument has measured
      health outcomes in terms of quality improvement from the users' perspective, and
      has also highlighted gaps between what the service offers in terms of quality and
      users' perceptions of what is delivered. The study demonstrates the importance of
      the professional role in quality improvement. ORIGINALITY/VALUE: Patient-centred
      quality improvement audit should be undertaken regularly so that both non
      clinical managers and health care professionals can establish whether or not they
      are providing services that are patient-friendly and effective from the user's
      viewpoint. In the course of their work, professionals and managers discuss
      patients and speak on their behalf in various forums, and knowing what patients
      actually expect and perceive before speaking on their behalf may be of great
      benefit in such instances.

PMID- 15974504
TI  - The impact of service user involvement in research.
AB  - PURPOSE: There are many examples of consumer involvement in NHS research but few
      studies have examined the impact of this on service development or the research
      process. This study, involving service user and carer researchers working
      alongside professional researchers, aimed to examine the development of one
      service user and carer research group in a mental health Trust.
      DERSIGN/METHODOLOGY/APPROACH: The research involved a review of existing
      literature on consumer involvement in research, a review of user involvement in
      research in South West Yorkshire Mental Health NHS Trust, a survey of consumers
      and NHS staff in the Trust, and a skills audit and training needs analysis of
      consumers. FINDINGS: The study identified the range and extent of consumer
      involvement and the impact of this on consumers and the Trust. Service users and
      carers were involved in a range of projects, mainly on the level of consultation
      or collaboration. The benefits for consumers were principally on a personal level
      and included gaining knowledge and experience, improved sense of well-being, self
      esteem, and confidence. The benefit for the Trust was in having a service user
      perspective and focus. However, there is a tendency to omit service users from
      planning and setting priorities. PRACTICAL IMPLICATIONS: The study pointed to the
      need to build the evidence base on consumer involvement in research, particularly
      in terms of how consumers can impact on setting research priorities and selecting
      appropriate methods. It identifies the need for more training for consumers and
      for NHS staff and for a more coherent strategy. ORIGINALITY/VALUE: This article
      will be of value to anyone who is at the start or in the early stages of their
      journey of consumer involvement. It identifies some of the practical issues faced
      by consumers and staff in working collaboratively, but also points to the
      benefits for all the stakeholders.

PMID- 15974505
TI  - Sampling for quality assurance of grading decisions in diabetic retinopathy
      screening: designing the system to detect errors.
AB  - PURPOSE: To evaluate various designs for a quality assurance system to detect and
      control human errors in a national screening programme for diabetic retinopathy.
      DESIGN/METHODOLOGY/APPROACH: A computer simulation was performed of some possible
      ways of sampling the referral decisions made during grading and of different
      criteria for initiating more intensive QA investigations. The effectiveness of QA
      systems was assessed by the ability to detect a grader making occasional errors
      in referral. FINDINGS: Substantial QA sample sizes are needed to ensure against
      inappropriate failure to refer. Detection of a grader who failed to refer one in
      ten cases can be achieved with a probability of 0.58 using an annual sample size
      of 300 and 0.77 using a sample size of 500. ORIGINALITY/VALUE: An unmasked
      verification of a sample of non-referrals by a specialist is the most effective
      method of internal QA for the diabetic retinopathy screening programme.
      Preferential sampling of those with some degree of disease may improve the
      efficiency of the system.

PMID- 15974506
TI  - Development of measures of individual leadership for health promotion.
AB  - PURPOSE: This purpose of this research was to develop and establish psychometric
      properties of scales measuring individual leadership for health promotion.
      DESIGN/METHODOLOGY/APPROACH: Scales to measure leadership in health promotion
      were drafted based on capacity assessment instruments developed by other
      provinces involved in the Canadian Heart Health Initiative (CHHI), and on the
      literature. Content validity was established through a series of focus groups and
      expert opinion appraisals and pilot testing. Psychometric analyses provided
      empirical evidence of the construct validity and reliability of the leadership
      scales in the baseline survey (n = 144) of the Alberta Heart Health Project.
      FINDINGS: Principal component analysis verified the construct of the leadership
      scales of personal work-related practices and satisfaction with work-related
      practices. Each of the theoretically a prior determined scales factored into two
      scales each for a total of four final scales. Scale alpha coefficients
      (Cronbach's alpha) ranged between 0.71 and 0.78, thus establishing good scale
      internal consistencies. RESEARCH LIMITATIONS/IMPLICATIONS: Limitations include
      the relatively small sample size used in determining psychometric properties. In
      addition, further qualitative work would enhance understanding of the complexity
      of leadership in health organizations. These measures can be used by both
      researchers and practitioners for the assessment leadership for health promotion
      and to tailor interventions to increase leadership for health promotion in health
      organizations. ORIGINALITY/VALUE: Establishing the psychometric properties and
      quality of leadership measures is an innovative step toward achieving capacity
      assessment instruments which facilitate evaluation of key relationships in
      developing health sector capacity for health promotion.

PMID- 15974507
TI  - Clinical leadership in health care: a position statement.
AB  - PURPOSE: This paper aims to briefly review leadership within the contemporary UK
      National Health Services (NHS) including Department of Health and Royal College
      of Nursing (RCN) initiatives. DESIGN/METHODOLOGY/APPROACH: It is argued that the
      concept of clinical leadership is a viable and important one, and is
      theoretically consistent with the contemporary social psychological literature on
      the importance of "local" leadership to effective organizational functioning.
      Field theory proposes that local influences (e.g. local management) on attitudes
      and behaviour will to a large extent mediate the impact of the organization (e.g.
      organisational structure and values) on (in this instance) health care delivery.
      FINDINGS: The reality of clinical leadership must involve a judicious blend
      effective management in the conventional sense with skill in transformational
      change in order to make real difference to the care delivery process. PRACTICAL
      IMPLICATIONS: For leadership initiatives to become truly culturally embedded into
      the "way we do things around here", they require more than just individual
      training and development. ORIGINALITY/VALUE: A view is offered for the practical
      interpretation of the clinical leadership concept in relationship terms. This
      will involve management of the relationship between health care professionals,
      between health care professionals and the "organizations" to which they are
      accountable and between health care professionals and service users.

PMID- 15974508
TI  - Access and utilization of health services by British Columbia's rural Aboriginal
      population.
AB  - PURPOSE: To provide a picture of the access and use of health services by
      Aboriginal British Columbians living in both reserve and off-reserve communities.
      DESIGN/METHODOLOGY/APPROACH: This project represents a collaborative effort
      between the University of British Columbia and multiple Aboriginal community
      partners. Between June and November 2003, 267 face-to-face interviews were
      conducted with Aboriginal persons in seven rural community organizations across
      the province. FINDINGS: This paper reports on the results of a survey of 267
      Aboriginal clients. It was found that a substantial number of survey respondents
      accessed health services provided by an Aboriginal person. Although most
      respondents felt that services were available, they also identified a number of
      concerns. These revolved around the need to travel for services, as well as a
      lack of access to more specialized services. A number of self-reported barriers
      to service were also identified. These findings have several policy implications
      and will be useful to service planners. RESEARCH LIMITATIONS/IMPLICATIONS:
      Several questions for additional research were identified including the need to
      establish an inventory of service problem areas and investigating service and
      benefit policy and community awareness issues. ORIGINALITY/VALUE: This paper
      provides policy makers with knowledge on the rural Aboriginal population, a
      population that has faced long standing problems in accessing appropriate health
      services.

PMID- 15974509
TI  - Risk management strategies in physical therapy: documentation to avoid
      malpractice.
AB  - PURPOSE: This article aims to highlight the importance of a complete and accurate
      medical record as it pertains to potential risk exposure in the outpatient
      physical therapy profession. DESIGN/METHODOLOGY/APPROACH: Basic charting rules,
      correction and alteration recommendations, documentation of telephone
      conversations, informed consent, exculpatory release forms and incident reports
      are discussed. Basic risk management strategies are reviewed that may reduce
      outpatient physical therapy practitioners' malpractice exposure. FINDINGS: The
      authors contend that quality and thorough documentation is as important as the
      quality of the care that is delivered to patients, since medical records are
      legal documents and serve as valuable evidence as to what transpired between
      patients and the healthcare providers. ORIGINALITY/VALUE: Practical documentation
      strategies are described in a manner that will inform physical therapists of
      their legal obligations relating to patient care.

PMID- 15974510
TI  - Employee care, a vital antecedent to customer care in the health care industry:
      an exploratory investigation of the employee satisfaction construct at North East
      Alabama Regional Medical Center.
AB  - PURPOSE: The paper reports on the conceptualization and measurement of the
      employee satisfaction construct at North East Alabama Regional Medical Center
      (RMC), Anniston, Alabama. The study sought to take a global attitudinal measure
      of employee satisfaction. DESIGN/METHODOLOGY/APPROACH: The employee satisfaction
      construct was evaluated through the use of an amended Brayfield-Rothe Index
      (BRI). The Index, in its original form, comprises an 18-item five-point Likert
      scale with items listed in both positive and negative format. The amended
      instrument comprised an additional 12 items addressing such issues as
      organizational culture and satisfaction with existing orientation, human resource
      policy and practice. The sample was drawn from all employees of the North East
      Alabama Regional Medical Center, Anniston, Alabama over a two-week period in
      November 2003. FINDINGS: The results have proved beneficial in revealing those
      core dimensions that comprise the employee satisfaction construct, at least as
      defined through the use of BRI at RMC. The Center has been able to identify those
      areas where performance should be maintained at present levels and those where
      improvement is needed. RESEARCH LIMITATIONS/IMPLICATIONS: The research is limited
      by the fact that it was cross-sectional in nature and in order to track real
      change/improvement over time, it should be repeated annually. It should also be
      stressed that the BRI was used to provide a global attitudinal measure of
      employee satisfaction only. When used as such, the author would recommend a
      certain amount of qualitative follow-up with willing participants in a focus
      group forum. This should allow for a richer interpretation of the results.
      PRACTICAL IMPLICATIONS: The results have proved beneficial in revealing those
      core dimensions that comprise the employee satisfaction construct, at least as
      defined through the use of BRI at RMC. The Center has been better placed to
      identify those areas where performance should be maintained at present levels and
      those where improvement is needed. ORIGINALITY/VALUE: The research demonstrates
      the value and relative simplicity of the BRI method.

PMID- 15974512
TI  - Quality assurance.

PMID- 15974511
TI  - Procurement performance measurement system in the health care industry.
AB  - PURPOSE: The rising operating cost of providing healthcare is of concern to
      health care providers. As such, measurement of procurement performance will
      enable competitive advantage and provide a framework for continuous improvement.
      The objective of this paper is to develop a procurement performance measurement
      system. DESIGN/METHODOLOGY/APPROACH: The paper reviews the existing literature in
      procurement performance measurement to identify the key areas of purchasing
      performance. By studying the three components in the supply chain collectively
      with the resources, procedures and output, a model is been developed.
      Additionally, a balanced scorecard is proposed by establishing a set of generic
      measures and six perspectives. A case study conducted at the Singapore Hospital
      applies the conceptual model to describe the purchasing department and the
      activities within and outside the department. FINDINGS: The results indicate that
      the material management department has already made a good start in measuring the
      procurement process through the implementation of the balanced scorecard.
      RESEARCH LIMITATIONS/IMPLICATIONS: There are many data that are collected but not
      properly collated and utilized. Areas lacking measurement include cycle time of
      delivery, order processing time, effectiveness, efficiency and reliability.
      Though a lot of hard work was involved, the advantages of establishing a
      measurement system outweigh the costs and efforts involved in its implementation.
      PRACTICAL IMPLICATIONS: Results of balanced scorecard measurements provide
      decision-makers with critical information on efficiency and effectiveness of the
      purchasing department's work. ORIGINALITY/VALUE: The measurement model developed
      could be used for any hospital procurement system.

PMID- 15974513
TI  - Quality management and employee commitment illustrated with examples from Dutch
      health care.
AB  - PURPOSE: To assess the relationship between quality management and employee
      commitment. DESIGN/METHODOLOGY/APPROACH: Analysis of the state of affairs with
      respect to (T)QM programs in The Netherlands based on the literature and
      interviews with key informants. FINDINGS: Description of an approach that tries
      to integrate employee commitment and quality management based on the concept of
      employees' psychological contracts with their organization (ideas about mutual
      obligations between them and their employer). RESEARCH LIMITATIONS/IMPLICATIONS:
      The interviews with key informants provide limited information: the study is done
      in only one country. Research in a broader context and on a larger scale would
      give a more general overview. PRACTICAL IMPLICATIONS: The crucial factor in
      making quality management work can better be described by "quality fails when
      employees' psychological contracts are neglected" than by "quality fails when the
      system fails". ORIGINALITY/VALUE: This paper highlights the essential
      relationship between quality management and employee commitment and offers
      suggestions on how to approach this issue.

PMID- 15974514
TI  - The impact of leading empowered organisations (LEO) on leadership development in
      nursing.
AB  - PURPOSE: This study sought to evaluate the impact and sustainability of the
      Leading Empowered Organisations (LEO) programme on the role of G Grade Nurse
      Managers, their colleagues and therefore on patient care at CHS.
      DESIGN/METHODOLOGY/APPROACH: A qualitative, inductive research methodology, which
      employed 360-degree research evaluation, was used. A purposive sample of four G
      Grade Nurse Managers was included. Each G Grade and eight of each of their
      colleagues were interviewed. Data were analysed according to the principles of
      thematic analysis. FINDINGS: There was evidence of a sustained impact of the LEO
      programme on G Grade Nurse Managers in relation to competence, action plans,
      delegation, communication strategies, problem solving, risk taking, leadership
      and management. The study also revealed a number of significant personal and
      contextual factors that affected the implementation of the LEO principles.
      Empowerment, or a lack of it, underpinned much of what occurred in the
      implementation of the LEO principles by the G Grades into practice.
      ORIGINALITY/VALUE: The findings indicated that both organisational and individual
      action is necessary to achieve leadership development. Organisations need to
      ensure that investment in leadership is not restricted to the LEO programme, but
      that it becomes a strategic priority.

PMID- 15974515
TI  - Assessing performance of multi-hospital organizations: a measurement approach.
AB  - PURPOSE: This paper aims to introduces a measure to assess the perceived
      effectiveness of multi-hospital organizations (MOs). DESIGN/METHODOLOGY/APPROACH:
      A sample of top managers of non-profit hospitals serves as the study setting.
      Data were collected via mail surveys. Usable responses were obtained from 189
      hospitals. The measure was developed by considering the instrumentality and
      effect components of a set of relevant motives for joining an MO. During the
      course of the study, three alternative formulations were examined. FINDINGS:
      Results show that the measures based on effect alone and a multiplicative
      combination of effect and instrumentality demonstrate sound psychometric
      properties. The recommendation here is to adopt the latter measure. RESEARCH
      LIMITATIONS/IMPLICATIONS: The study was limited to a particular sample.
      Replications among other samples are needed to validate the current findings.
      Also, because the exact content of the objective function of a hospital for
      joining an MO is not necessarily constant over time, there is a need to conduct
      similar studies on a periodic basis. PRACTICAL IMPLICATIONS: The measure
      recommended here uses multiplicative/weighted instrumentality and effect scores
      as opposed to only the instrumentality or effect scores. This makes it possible
      to go beyond the mere "why" or "how" questions. Simultaneous consideration of
      instrumentality and effect dimensions affords a richer and more relevant
      understanding. ORIGINALITY/VALUE: Valid and reliable measures of performance are
      critical for both managerial and research purposes. The measure proposed in the
      current study could be used in structural equation models to investigate the
      effect of individual actions on performance and the impact of performance on
      other outcome measures (e.g. intentions to stay in an MO).

PMID- 15974516
TI  - Quality management in Malaysian public health care.
AB  - PURPOSE: The main aim of the study is to provide an empirical analysis of quality
      management practice among Malaysian Ministry of Health hospital employees,
      ranging from medical specialists to health attendants.
      DESIGN/METHODOLOGY/APPROACH: Self-administered questionnaires collected data and
      cluster sampling used to select hospitals, while stratified random sampling
      selected employee respondents. The research was limited to peninsular Malaysian
      public health care. FINDINGS: A total of 23 public hospitals participated in the
      survey, including the National Referral Centre, which is based in Hospital Kuala
      Lumpur. Eight quality management practices were identified in Malaysian public
      hospitals: continuous improvement, strategic planning, quality assurance,
      teamwork, leadership and management commitment, employee involvement and
      training, management by fact, and supplier partnership. Support for quality
      management was found to be lowest among the physicians. ORIGINALITY/VALUE: The
      article fills a lacuna in the health care quality management empirical research
      literature. The main recommendation is for the Malaysian Ministry of Health to
      gamer physicians' support in its quality endeavours.

PMID- 15974517
TI  - Measuring service quality in a hospital colposcopy clinic.
AB  - PURPOSE: The issues surrounding the measurement and provision of service quality
      in a health care setting are becoming increasingly important to nursing. This
      research study aims to apply the SERVQUAL measurement instrument in a Scottish
      colposcopy clinic. DESIGN/METHODOLOGY/APPROACH: The study involved adapting the
      SERVQUAL instrument to the colposcopy setting and asking a sample of patients to
      complete the questionnaire. Patient expectations of service were obtained on
      first attendance at the clinic. Patient perceptions of service received were
      obtained on completion of treatment. Perceptions and expectations are then
      compared to identify where the largest service gaps exist. FINDINGS: Although
      patient satisfaction with the overall service provided was generally high, the
      instrument provided evidence of where specific service improvements were needed.
      The largest service quality gap was for the reliability of service. The research
      also revealed the need for improved premises. RESEARCH LIMITATIONS/IMPLICATIONS:
      Although the study has a limited sample size, it does appear that the SERVQUAL
      instrument has a useful diagnostic role to play in assessing and monitoring
      service quality in nursing, enabling nursing staff to identify where improvements
      are needed from the patients' perspective. The study has raised a number of
      issues which would form the basis for useful further research. PRACTICAL
      IMPLICATIONS: Service quality from the patients' perspective should be routinely
      monitored and assessed. ORIGINALITY/VALUE: The findings should be useful to
      nursing staff seeking to assess, and improve, service quality.

PMID- 15974518
TI  - Influence of angiotensin-converting enzyme gene insertion/deletion polymorphism
      on rheumatic valve involvement, valve severity and subsequent valve
      calcification.
AB  - BACKGROUND AND AIM OF THE STUDY: The relationship between the severity of chronic
      rheumatic heart disease (RHD) and predisposing factors is unknown, and genetic
      predictors for severe scarring and calcification of the mitral valve are not well
      defined. A high angiotensin-converting enzyme (ACE) activity has been
      demonstrated in valve tissue. Thus, a case-control study was conducted to
      investigate any possible relationship between ACE gene polymorphisms and chronic
      mitral valve disease severity and calcification. METHODS: This case-control study
      included 82 patients (24 males, 58 females; mean age 40.3 +/- 14.7 years) with
      chronic rheumatic mitral valve, and 154 control subjects (53 males, 101 females;
      mean age 43.4 +/- 13.4 years). ACE gene insertion/deletion (I/D) polymorphisms
      were identified using polymerase chain reaction methods. RESULTS: Among RHD
      subjects, 31 (30.6%) were D/D, 25 (32.7%) were I/D, and 26 (18.8%) were I/I.
      Among controls, 57 (57.4%) were D/D, 69 (61.3%) were I/D, and 28 (35.2%) were
      I/I. The frequency of ACE I/I genotype was higher in RHD subjects than in
      controls (chi2 = 7.4, df = 2, p < 0.030; D/D versus I/D versus I/I), or (chi2 =
      5.5, df = 1, p < 0.019; DD + ID versus II). Predisposition to RHD was
      significantly less frequent in the D/D genotype. There was no statistically
      significant difference in the genetic analysis of RHD with respect to mitral
      valve score, severity of mitral regurgitation and left atrial diameter. Mitral
      valve calcification was significantly associated with a higher frequency of I/I
      genotype and I/D genotype than D/D genotype alone (chi2 = 6.2, df = 2, p =
      0.043). The ACE I/I genotype was associated with a predisposition to a greater
      risk of severe calcific valve disease. CONCLUSION: The ACE I/I genotype is more
      common in patients with rheumatic valve disease than in the normal population.
      This suggests that the ACE gene polymorphism may be involved in the pathogenesis
      of rheumatic heart disease.

PMID- 15974519
TI  - 'Frozen' posterior mitral leaflet in rheumatic mitral stenosis: incidence and
      impact on outcome of balloon mitral commissurotomy.
AB  - BACKGROUND AND AIM OF THE STUDY: The incidence and clinical significance of
      immobile and 'frozen' posterior mitral leaflet (FPML) were evaluated in the
      pathophysiology and immediate outcome of patients with severe pliable mitral
      stenosis (MS) undergoing percutaneous balloon mitral commissurotomy (PBMC).
      METHODS: During the past four years, 30 'ideal' patients (mean age 46 +/- 8
      years) with Wilkins' score <8, bilateral commissural fusion and absence of
      commissural calcification underwent peri-procedural echocardiographic analysis.
      Anterior mitral leaflet (AML) mobility index (MI), chordae tendineae (CT) length,
      and mitral valve area (MVA) were evaluated. RESULTS: Pre-procedure FPML was noted
      in 28 patients (93%). All patients achieved MVA > or = 1.5 cm2. Post-procedure
      MVA in patients with bilateral commissural splitting was 1.9 +/- 0.2 cm2 versus
      1.6 +/- 0.1 cm2 in patients with unilateral commissural splitting (p < 0.05). CT
      lengths directed to the AML and PML were 15 +/- 2 mm and 8 +/- 2 mm, respectively
      (p < 0.05). MI of the AML before and immediately after PBMC was 0.4 and 0.6,
      respectively (p < 0.05). None of the patients with FPML showed improved mobility
      following successful PBMC. CONCLUSION: FPML may be found in most patients with
      pliable MS. It is mainly a result of short, rigid and fused CT directed to the
      PML. A 'single-wing door' or a unicuspid valve may be used as a model for
      rheumatic pliable MS. It is suggested that pre-procedure leaflet morphology and
      functional assessment should focus on the AML.

PMID- 15974520
TI  - Altered mitral valve kinematics with atrioventricular and ventricular pacing.
AB  - BACKGROUND AND AIM OF THE STUDY: Pacing-induced mitral regurgitation contributes
      to the 'pacemaker syndrome', which usually is observed with ventricular (V)
      pacing, but has also been reported with atrioventricular (AV) sequential pacing.
      Effects of different pacing modes on 3-D kinematics of the mitral apparatus are
      incompletely understood. METHODS: Radio-opaque markers were placed on the left
      ventricular (LV) and mitral apparatus including the annulus, leaflets and
      papillary muscles of eight sheep. Hemodynamic and 3-D dynamic marker geometry
      were obtained one week later with biplane videofluoroscopy (60 Hz) during atrial
      (pacing site = left atrium), AV-sequential (140 ms interval) and (anterolateral
      LV epicardial) ventricular pacing. RESULTS: Compared with A-pacing (*p <0.05): 1)
      The regurgitant fraction increased with both AV- and V-pacing (A: 6 +/- 3%, AV:
      13 +/- 3%*, V: 15 +/- 2%*); 2) AV and V-pacing delayed closure at the leaflet
      center (A: 21 +/- 10 ms, AV: 52 + 5 ms*, V: 92 +/- 6 ms*) and posterior
      commissure (A: 17 +/- 10 ms, AV: 46 +/- 8 ms*, V: 94 +/- 6 ms*). V-pacing delayed
      valve closure at the anterior commissure (A: 27 +/- 9 ms, V: 94 +/- 6 ms*); 3)
      The end-diastolic leaflet opening angle was greater with AV- and V-pacing
      (anterior mitral leaflet (AML): A: 32 +/- 2 degrees, AV: 41 +/- 4 degrees*, V: 46
      +/- 4 degrees*; posterior mitral leaflet (PML): A: 56 +/- 4 degrees, AV: 62 +/- 3
      degrees*, V: 68 +/- 3 degrees*); 4) 'Effective' end-diastolic PML midline length
      was reduced with AV- and V-pacing (A: 11.2 +/- 0.7 mm, AV: 10.0 +/- 0.4 mm*, V:
      10.2 +/- 0.3 mm*), as was the distance from each papillary muscle (PM) tip to the
      AML edge ('effective' chordal length) close to the commissures (anterior PM-AML:
      A: 31.5 +/-1.8 mm, AV: 30.5 +/- 1.9 mm*, V: 29.7 +/- 1.8 mm*; posterior PM-AML:
      A: 33.7 +/- 1.8 mm, AV: 33.1 +/- 1.9 mm*, V: 32.8 +/- 1.9 mm*). CONCLUSION: Both
      ventricular and AV-sequential-pacing resulted in a more widely opened valve at
      end-diastole and leaflet dyssynchrony with delayed mitral valve closure and early
      systolic mitral regurgitation. These alterations which result in pacing-induced
      mitral regurgitation may be clinically important in patients with impaired LV
      function.

PMID- 15974521
TI  - Effects of papillary muscle position on chordal force distribution: an in-vitro
      study.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral insufficiency, a common and morbid
      pathology, has been related to topological changes in the left ventricle. These
      changes may affect mitral leaflet coaptation by displacing the tips of the
      papillary muscles (PMs), subsequently changing the tension distribution on the
      chordae tendineae. Therefore, further understanding of the effects of PM
      displacement on chordal force distribution is required. METHODS: Six human and
      five porcine mitral valves were studied in a physiological left heart simulator.
      Cardiac output and transmitral pressure were recorded online and maintained
      within physiological ranges. Force transducers were placed on six chordae
      tendineae to measure chordal force distribution. Tension on individual chordae
      tendineae was recorded online during the cardiac cycle. The experiment was
      conducted for eight different PM positions, which were constructed from 5-mm
      vectorial displacements from the normal PM position. RESULTS: The anterior strut
      chord showed significant (p <0.05) variations in peak systolic tension (PST) for
      those positions associated with apical motion of the PMs. The posterior
      intermediate chord also showed significant variations in PST for positions
      associated with apical displacement of the PMs, whereas posterior displacement of
      the PMs resulted in a reduction in tension. In contrast, both the anterior
      marginal and posterior marginal chords showed a relatively uniform PST for the
      eight different PM positions. The posterior basal and commissural chords were the
      most sensitive to tension variations due to PM displacement. These chords showed
      relatively large and significant (p <0.05) variations in PST for most of the
      different PM displacements. CONCLUSION: The effects of PM relocation on chordal
      tension depended on chordal type. Chords which insert closer to the annulus were
      more sensitive to PM displacement, whereas those further from the annulus, the
      marginal chords, were the least sensitive to PM displacement.

PMID- 15974522
TI  - Infective endocarditis: mid-term prognosis in patients with good in-hospital
      outcome.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to analyze the mid-term
      prognosis of infective endocarditis (IE) in patients managed with medical therapy
      during the in-hospital phase and who had a good initial outcome. Comparison was
      made with the prognosis of patients treated surgically during this period.
      METHODS: A total of 151 patients diagnosed with IE was studied, and in-hospital
      outcome, clinical characteristics and mid-term follow up data were analyzed. The
      main end-point was a composite of death and need for surgical repair. RESULTS:
      Among 151 patients, 84 (56%) underwent surgery or died during the in-hospital
      phase, while 67 patients (44%) received medical treatment and were discharged
      clinically stable with a final diagnosis of healed infective endocarditis. A
      better baseline profile was seen in the medically treated group, but outcome in
      this group showed extensive mid-term morbidity/mortality. In total, 52.2% of
      patients underwent surgery to correct complications and 60% died as a consequence
      of the disease. The event-free survival rate was 20% at five years. CONCLUSION:
      Despite a favorable in-hospital clinical course and successful medical treatment,
      patients with IE are at risk of late complications that result in a need for
      surgical repair, or in death. A close follow up should be made in order to treat
      late complications.

PMID- 15974523
TI  - Peripheral mycotic aneurysms in infective endocarditis.
AB  - BACKGROUND AND AIM OF THE STUDY: Today, infective endocarditis (IE) remains a
      severe illness, with high mortality and morbidity. Mycotic aneurysms (MAs) are
      rare complications of IE. For most patients, surgical intervention represents the
      only hope for radical cure of extracranial MAs, and survival. METHODS: A total of
      238 patients with IE was treated at the authors' center between January 1990 and
      December 2003. Among these patients, 10 underwent surgical intervention due to
      peripheral MAs. RESULTS: Concomitant surgery for intracardiac and extracardiac
      pathology was applied in three patients with native valve endocarditis to excise
      infected material. Aneurysmectomy and revascularization were performed in four
      patients with native endocarditis, and in three with prosthetic valve
      endocarditis (PVE). The intracardiac pathologies of these seven patients were
      treated with antimicrobial agents. Eight patients underwent surgery after
      completion of three weeks' antibiotic therapy. An autologous saphenous vein
      interposition was performed in eight patients, but in two cases, due to size
      discrepancy, a polytetraflouroethylene (PTFE) graft was chosen as the initial
      conduit to achieve arterial continuity. Saphenous vein graft rupture occurred in
      one patient; a PTFE graft was used to achieve second revascularization. Limb
      salvage was achieved in nine patients. Below-knee amputation was necessary in one
      patient; this was due to prior embolism of the distal arterial tree. Two patients
      died, one due to cerebral embolism and another to rupture of undiagnosed visceral
      MA. All other patients remain alive, without complications. CONCLUSION: Complete
      revascularization should be essential to treat peripheral MA in IE. Adequate
      resection, appropriate parenteral administration of antimicrobial agents and size
      discrepancy are far more important factors than the type of graft material in
      preventing suture-line infection and vessel or graft rupture.

PMID- 15974524
TI  - An unusual bacterium, Aerococcus viridans, and four cases of infective
      endocarditis.
AB  - Four cases are described of Aerococcus viridans endocarditis with favorable
      outcome, focusing on the clinical picture. Extracardiac findings (e.g.
      neurological, renal, musculoskeletal, intra-abdominal) in infective endocarditis
      (IE) have been recognized more frequently in recent years, and may delay the
      diagnosis and have a negative influence on the prognosis. Aerococcus viridans, a
      very rare microorganism causing invasive infections, has been associated with
      bacteremia, septic arthritis, and especially IE. As expected, the strains
      isolated were susceptible to penicillins, trimethoprim/sulfamethoxazole, and
      glycopeptides. Medical therapy was sufficient to cure IE in two patients, while
      two others required surgical intervention.

PMID- 15974525
TI  - Mitro-aortic infective endocarditis produced by Erysipelothrix rhusiopathiae:
      case report and review of the literature.
AB  - Endocarditis produced by Erysipelothrix rhusiopathiae is an uncommon disease in
      humans. This bacterial species is found worldwide as a commensal or a pathogen in
      many animals. Infection in humans is usually due to occupational exposure. The
      case is reported of a 43-year-old male parrot breeder with native aortic and
      mitral valve endocarditis and NYHA class II heart failure at six months after
      wound infection. The patient was discharged after six weeks' treatment with
      intravenous penicillin G and replacement of the mitral and aortic valves due to
      severe regurgitation. At one year after surgery the patient was asymptomatic and
      infection-free.

PMID- 15974526
TI  - Impact of intraoperative echocardiography/surgery team on successful mitral valve
      repair: a community hospital experience.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral valve (MV) repair is generally accepted
      as the preferred treatment of mitral regurgitation (MR) with MV prolapse
      secondary to myxomatous mitral valve disease (MMVD). However, the incidence of
      successful valve repair is variable between hospitals and among different
      surgeons at one hospital, and often results in needless MV replacement. The study
      aim was to measure the impact of a dedicated echocardiography/surgery team on MV
      repair at a community hospital. METHODS: The outcome was analyzed of a group of
      116 consecutive patients with severe MR secondary to MMVD who underwent surgery
      by the same surgeon over a six-year period. A dedicated team approach, comprising
      one echocardiographer and one surgeon was established in January 1999. The
      results of MV repair between 1996 and 1998 (group I; n = 37) were compared to
      results obtained between 1999 and 2001 (group II; n = 79). RESULTS: In group I,
      MV repair was attempted in 25 patients (67.6%) and was successful in 21 (56.8%).
      In group II, MV repair was attempted in 68 patients (86.1%) and was successful in
      67 (84.8%). The success rate between groups was significantly (p = 0.001)
      different. The rate of successful MV repair in patients with a diffusely
      redundant prolapsing valve involving both leaflets and multiple segments with
      chordae elongation was significantly higher in group II (14/20; 70%) than in
      group I (1/6; 14.3%) (p = 0.011). CONCLUSION: A greater incidence of successful
      MV repair, even with more diffuse pathology of MMVD, was realized following the
      institution of dedicated echocardiography/surgery team at a community hospital.
      It is proposed that a combination of dedicated intraoperative echocardiography
      and surgical expertise is required for optimal results in MV repair.

PMID- 15974527
TI  - High concordance of invasive and echocardiographic mean pressure gradients in
      patients with a mechanical aortic valve prosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: Conflicting data exist regarding the accuracy of
      echocardiographic Doppler gradients compared to invasive pressure gradients in
      the hemodynamic assessment of patients with prosthetic aortic valves. The study
      aim was to determine the correlation between these measurements for mechanical
      single- and double-leaflet aortic valve prostheses in vivo. METHODS: Forty-four
      patients with an aortic valve prosthesis were included in this prospective study.
      Transthoracic echocardiography was performed immediately before the invasive
      measurements. Left ventricular pressure measurements were achieved by either
      atrial transseptal puncture and antegrade, transmitral left ventricular
      catheterization or--in the case of mitral valve replacement--direct left
      ventricular puncture. RESULTS: Comparison of echocardiographic and invasive mean
      pressure gradients of all examined aortic prosthetic valves revealed a Pearson
      correlation r = 0.59 (p < 0.001). The mean pressure gradient was overestimated by
      7.4 mmHg with echocardiography. Classifying patients into clinically relevant
      categories (mild, moderate, severely increased pressure gradient) resulted in a
      kappa value of 0.72 and an agreement of 86.4%. There was no relevant difference
      between single- and double-leaflet valves. CONCLUSION: A high concordance was
      found between echocardiographic and invasive mean pressure gradients in vivo.
      Invasive measurements of the prosthetic valve gradients therefore seem to be
      indicated only in patients with contradictory echocardiographic and clinical
      findings.

PMID- 15974528
TI  - Neuropsychological deficits after mechanical aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Studies using transcranial Doppler monitoring
      have identified high-intensity transient signals (HITS) after mechanical valve
      replacement. Although cognitive dysfunction in relation to HITS was reported in
      some studies, the current data basis is inconsistent. The study aim was to
      investigate the long-term effects of HITS on cognitive function. METHODS: Forty
      patients who had undergone mechanical valve replacement (mean 5.3 years
      previously) participated in the study. HITS-measurements were performed on the
      day of neuropsychological assessment. Patients were allocated to HITS-high and
      HITS-low groups on the basis of the median HITS-rate. Both patient groups
      completed a neuropsychological test battery and were compared to healthy
      controls. RESULTS: Both patient groups showed verbal and visual memory deficits
      in comparison with controls. The HITS-high group scored lower on verbal memory
      compared to the HITS-low group. In addition, the HITS-high group showed executive
      deficits when compared to the HITS-low group and controls. The significant
      effects with respect to verbal memory and executive functions remained after
      extracorporeal circulation time differences were controlled for. CONCLUSION: The
      study results imply that heart valve replacement with mechanical prostheses may
      be associated with mild cognitive impairment. The differential impairment pattern
      of the high- and low-HITS groups further suggests that the number of HITS may be
      of critical importance. The observed memory impairments were consistent with the
      view that cognitive dysfunction after valve replacement may be due to temporal
      lobe dysfunction. However, future studies are required to investigate the
      association of number of HITS, cerebral changes and cognitive function in further
      detail.

PMID- 15974529
TI  - Can regurgitant flow damage the left atrial endothelium in patients with
      prosthetic mechanical heart valves?
AB  - BACKGROUND AND AIM OF THE STUDY: Previous in-vitro studies of mechanical heart
      valves (MHVs) in the closed position demonstrated the formation of regurgitant
      flows, with bubbles and jets forming vortices during each systole. The study aim
      was to determine whether the regurgitant flow observed in patients with MHVs can
      damage the left atrial endothelium, due to shear stresses exerted on the
      endothelial layers. This objective has been accomplished by appropriate in-vitro
      simulation experiments. METHODS: In these experiments, leakage flow through
      several commercial MHVs was investigated. The geometry of the set-up closely
      resembled that of the left atrial anatomy. Water was forced through the slit of a
      closed MHV and directed toward the hemispherical cup coated with fluorescent
      paint. The flow field between the valve and the cup was photographed using high
      speed videography, from which local velocities were measured, using digital
      particle imaging velocimetry. Qualitative damage to the surface of the cup was
      assessed from the amount of fluorescent paint removed from the cup. RESULTS: The
      experimental results and calculations indicated that flows through the gaps of
      the closed valves were sufficient to generate strong vortices, with velocities
      near the atrial wall in the range of 0.5 to 4.0 m/s, depending on the valve. This
      led to high shear stresses on the left atrial wall, which far exceeded
      physiologically acceptable levels. CONCLUSION: The calculated shear stresses
      exceeded by orders of magnitude the maximum physiologically tolerated stresses.
      This suggests that shear stresses associated with regurgitant jets in MHVs may
      damage the endothelial cells, leading to the activation of the inflammatory
      reaction, enhanced procoagulation, platelet activation and aggregation, and
      mechanical cell denudation.

PMID- 15974530
TI  - Calcification of human valve interstitial cells is dependent on alkaline
      phosphatase activity.
AB  - BACKGROUND AND AIM OF THE STUDY: The calcification of heart valves is associated
      with valve degeneration and failure, but the mechanisms involved are poorly
      understood. The presence of lamellar bone has been demonstrated in calcified
      aortic valves. Since osseous calcification is closely associated with alkaline
      phosphatase (ALP) activity, it was hypothesized that ALP activity might be
      implicated in the calcification of isolated leaflet interstitial cells (ICs).
      METHODS: Human valve leaflet ICs were isolated from transplant-explanted hearts
      at the time of transplantation (n = 12). RESULTS: Isolated leaflet ICs expressed
      the fibroblast-specific antigen (100% of cells) and smooth muscle (SM) alpha
      actin (70-80% of cells), but osteoblastic markers were not expressed. Cultured
      ICs did not calcify spontaneously, however when the growth medium was
      supplemented with beta-glycerophosphate (an organic phosphate) it induced the
      formation of calcified nodules that expressed osteonectin and ALP, but not SM
      alpha-actin. Beta-glycerophosphate-induced calcification of ICs showed a time
      dependent effect on the calcium content of treated cells over a 14-day period.
      ALP activity was considerably increased in beta-glycerophosphate-treated ICs, and
      this correlated with the calcium content (r = 0.5: p = 0.01). Levamisol (an ALP
      inhibitor) inhibited the beta-glycerophosphate-induced calcification process, as
      well as the expression of osteoblastic differentiation markers. CONCLUSION:
      Isolated and cultured leaflet ICs did not calcify spontaneously, though organic
      phosphate induced the formation of calcified nodules that expressed osteoblastic
      markers. The calcification of isolated ICs was seen to be dependent on ALP
      activity.

PMID- 15974531
TI  - Prevention of porcine aortic wall calcification by acellularization: necessity
      for a non-glutaraldehyde-based fixation treatment.
AB  - BACKGROUND AND AIM OF THE STUDY: Acellularization prevents cell-mediated
      calcification of the aortic wall, but the inflammatory response towards the
      unfixed tissue is problematic. Two additional fixation methods, applied after
      tissue acellularization, were studied. METHODS: Porcine aortic wall samples were
      randomized into four groups: (1) Standard fixation with glutaraldehyde (GA); (2)
      acellularization by a combined method of enzymes (DNase, RNase) and a detergent
      (Triton X-100); (3) acellularization followed by standard GA fixation; (4)
      acellularization followed by photo-oxidation. Samples were implanted into the
      wall of both jugular veins of six juvenile sheep. Tissue was explanted after
      three months and evaluated by X-radiography, light and electron microscopy, and
      calcium content (cc) measurement (atomic absorption spectrometry). Auto
      fluorescence of elastic fibers was used to identify the relationship between
      calcific deposits and elastin. RESULTS: GA-fixed aortic wall samples showed clear
      mineralization (cc 41.6 +/- 17.8 microg/mg), occurring predominantly at the level
      of cell remnants, as confirmed by electron- and fluorescence microscopy, locating
      calcific deposits in between elastic fibers. Acellularized aortic wall fragments
      were calcified significantly less, but an important (non-infectious) inflammatory
      response caused elastolysis and subsequent calcification of the elastic fibers
      (cc 5.6 +/- 2.8 microg/mg). Acellularized and GA-fixed fragments revealed
      important, inhomogeneously spread calcific deposits (cc 24.7 +/- 10.0 pg/mg).
      Photo-oxidized samples remained free from calcification (cc 0.82 +/- 1.6
      microg/mg). CONCLUSION: Acellularization is a promising tool in the prevention of
      porcine aortic wall calcification, but additional tissue fixation is necessary to
      prevent structural degeneration. GA fixation after acellularization causes
      important inhomogeneous tissue mineralization. Photo-oxidation combines optimal
      tissue fixation with superior anticalcification characteristics.

PMID- 15974532
TI  - Development of aortic valve sclerosis in a rabbit model of atherosclerosis: an
      immunohistochemical and histological study.
AB  - BACKGROUND AND AIM OF THE STUDY: It has been suggested that aortic valve
      sclerosis (AVS) is an atherosclerotic disease process that can proceed to aortic
      stenosis. The absence of reports studying an animal model of the early stages of
      this disease has precluded the development of preventive therapeutic strategies.
      A cholesterol-fed (0.25% cholesterol in chow) rabbit model of atherosclerosis
      that is characterized by a moderate level of hypercholesterolemia was studied to
      determine its efficacy as a model of early AVS. Cellular, structural and
      morphological changes in the aortic valves of these rabbits were studied.
      METHODS: Twenty rabbits were assigned randomly to four experimental groups: Group
      1 received normal chow for 40 weeks; group 2 received 0.25% cholesterol
      supplemented chow for 20 weeks; group 3 received 0.25% cholesterol-supplemented
      chow for 40 weeks; and group 4 received 0.25% cholesterol-supplemented chow for
      20 weeks followed by normal chow for an additional 20 weeks. The aortas and
      aortic valves were analyzed using immunohistochemical and histological methods to
      detect cellular and structural components of the developing lesions. RESULTS: All
      rabbits in groups 2, 3 and 4 developed atherosclerotic lesions in their aortas.
      Aortic valves from these animals demonstrated thickening, lipid deposition, a
      change in collagen content and organization, a reorganization of elastin, and the
      presence of both macrophage infiltrate and osteopontin. CONCLUSION: These
      findings were consistent with the suggestion of a link between atherosclerosis
      and AVS. Results were also similar to changes reported in human sclerotic aortic
      valves, suggesting the suitability of this rabbit model of atherosclerosis as a
      model for AVS.

PMID- 15974533
TI  - Non-linear fluid-coupled computational model of the mitral valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The dynamics of the mitral valve result from the
      synergy of left heart geometry, local blood flow and tissue integrity. Herein is
      presented the first coupled fluid-structure computational model of the mitral
      valve in which valvular kinematics result from the interaction of local blood
      flow and a continuum representation of valvular microstructure. METHODS: The
      diastolic geometry of the mitral valve was assembled from previously published
      experimental data. Anterior and posterior leaflets were modeled as networks of
      entangled collagen fibers, embedded in an isotropic matrix. The resulting non
      linear continuum description of mitral tissue was implemented in a three
      dimensional membrane formulation. Chordal tension-only behavior was defined from
      experimental tensile tests. The computational model considered the valve immersed
      in a domain of Newtonian blood, with an experimentally determined viscosity
      corresponding to a shear rate of 180 s(-1) at 37 degrees C. Ventricular and
      atrial pressure curves were applied to ventricular and atrial surfaces of the
      blood domain. RESULTS: Peak closing flow and volume were 51 ml/s and 1.17 ml,
      respectively. Papillary muscle force ranged dynamically between 0.0 and 2.6 N.
      Acoustic pressure (RMS) was found to be 3.3 Pa, with a peak frequency of 72 Hz at
      0.064 s from the onset of systole. Model predictions showed excellent agreement
      with available transmitral flow, papillary force and first heart sound (S1)
      acoustic data. CONCLUSION: The addition of blood flow and an experimentally
      driven microstructural description of mitral tissue represent a significant
      advance in computational studies of the mitral valve. This model will be the
      foundation for future computational studies on the effect of pathophysiological
      tissue alterations on mitral valve competence.

PMID- 15974534
TI  - Three-dimensional asymmetrical modeling of the mitral valve: a finite element
      study with dynamic boundaries.
AB  - BACKGROUND AND AIM OF THE STUDY: Previous computational studies of the normal
      mitral valve have been limited because they assumed symmetrical modeling and
      artificial boundary conditions. The study aim was to model the mitral valve
      complex asymmetrically with three-dimensional (3-D) dynamic boundaries obtained
      from in-vivo experimental data. METHODS: Distance tracings between ultrasound
      crystals placed in the sheep mitral valve were converted into 3-D coordinates to
      reconstruct an initial asymmetric mitral model and subsequent dynamic boundary
      conditions. The non-linear, real-time left ventricular and aortic pressure loads
      were acquired synchronously. A quasi-static solution was applied over one cardiac
      cycle. RESULTS: The mitral valve leaflet stress was heterogeneous. The trigones
      experienced highest stresses, while the mid-anterior annulus between trigones
      experienced low stress. High leaflet stress was observed during peak pressure
      loading. During isovolumic relaxation, the leaflets were highly stretched between
      the anterolateral trigone and the posteromedial commissure, resulting in a
      prominent secondary leaflet stress re-increment. This has not been observed
      previously, as symmetric models with artificial boundary conditions were studied
      only in the ejection phase. CONCLUSION: Here, the first asymmetrical mitral valve
      model synchronized with 3-D dynamic boundaries and non-linear pressure loadings
      over the whole cardiac cycle based on in vivo experimental data is described.
      Despite its limitations, this model provides new insights into the distribution
      of leaflet stress in the mitral valve.

PMID- 15974535
TI  - Predicting ATS Open Pivot heart valve performance with computational fluid
      dynamics.
AB  - BACKGROUND AND AIM OF THE STUDY: In-vitro studies on the ATS heart valve have
      indicated that valve opening is less in an expanding conduit than in a straight
      conduit. METHODS: Bileaflet valve behavior was studied using a new computational
      fluid-structure interaction model. A three-dimensional model of the ATS valve was
      studied in two geometries, simulating the valve in a geometry with sudden
      expansion downstream of the valve, and in a straight conduit. Mitral and aortic
      flow patterns were simulated. RESULTS: The ATS valve in the expanding geometry
      showed opening to a maximum angle of 77.5 degrees; this was confirmed in previous
      clinical and in-vitro studies. The mean and maximum transvalvular Doppler
      pressure gradients were 1.1 and 4.3 mmHg, respectively. The maximum shear stress
      calculated on the leaflet was 25 Pa. Maximum opening of the valve was achieved in
      the straight conduit; with mean and maximum pressure gradients of 2.1 and 4.6
      mmHg, respectively. The maximum shear stress calculated on the leaflet was 35 Pa.
      CONCLUSION: The results of this numerical study confirmed that valve hemodynamics
      and leaflet motion were dependent on the geometrical conditions of the valve: the
      presence of a diverging flow influenced the maximum opening angle of the valve
      leaflets. This model could be used to predict pressure gradients, effective
      orifice area, performance index and shear stress loading of mechanical heart
      valves, and in future will serve as a major research tool to characterize the
      hemodynamics of existing and new mechanical heart valves.

PMID- 15974536
TI  - Aortic root dynamics are asymmetric.
AB  - BACKGROUND AND AIM OF THE STUDY: The presence of conformational changes in the
      aortic root during the cardiac cycle is well known, but precise information on
      time-related changes at each level of the root is lacking. METHODS: High
      resolution, 3D sonomicrometry (200 Hz) was applied in an acute sheep model.
      Twelve crystals were implanted in eight sheep at each base (n = 3), commissure (n
      = 3), sinotubular junction (n = 3) and ascending aorta (n = 3). Under stable
      hemodynamic conditions, geometric changes of the perimeter of each sinus of
      Valsalva, sinus height, and twist and root tilt angles were time-related to left
      ventricluar (LV) and aortic pressures. RESULTS: Expansion of the perimeter of the
      three sinuses of Valsalva was homogeneous, but in significantly different
      proportions (p < 0.001): the right sinus expanded (+32.4 +/- 2.4%) more than the
      left (+29.3 +/- 3.2%), and more than the non-coronary (NC) sinus (+25.8 +/-
      1.7%). A similar pattern was found for aortic root height: right greater than
      left, and left greater than NC sinus (p < 0.001). This asymmetry resulted in
      changes of the root's twist and tilt angles. Although the twist deformation was
      consistent for each sheep, no general pattern was found. The aortic root tilt
      angle (between the basal plane and the commissural plane) was 16.3 +/- 1.5
      degrees at end-diastole (angle oriented posteriorly and to the left). During
      systole, it was reduced by 6.6 +/- 0.5 degrees, aligning the LV outflow tract
      with the ascending aorta. This tilt angle returned to its original value after
      valve closure. CONCLUSION: Aortic root expansion is asymmetric, generating
      precise changes in its tilt angle. During systole, tilt angle reduction resulted
      in a straight cylinder that probably facilitates ejection; during diastole, the
      tilt angle increased, probably reducing leaflet stress. These findings should
      impact upon surgical procedures and the design of new prostheses.

PMID- 15974537
TI  - In-vitro assessment of the functional performance of the decellularized intact
      porcine aortic root.
AB  - BACKGROUND AND AIMS OF THE STUDY: Tissue-engineered heart valves offer the
      potential to deliver a heart valve replacement that will develop with the young
      patient. The present authors' approach is to use decellularized aortic heart
      valves reseeded in vitro or in vivo with the patient's own cells. It has been
      reported that treatment of porcine aortic valve leaflets with 0.1% (w/v) sodium
      dodecyl sulfate (SDS) in hypotonic buffer produced complete leaflet acellularity
      without affecting tissue strength. The present study aim was to investigate the
      effect of an additional treatment incorporating 1.25% (w/v) trypsin and 0.1%
      (w/v) SDS on the biomechanics and hydrodynamics of the aortic root. This
      treatment has been shown to produce decellularization of both the aorta and valve
      leaflets. METHODS: Fresh porcine aortic roots were treated to reduce the
      thickness of their aortic wall, and incubated in hypotonic buffer for 24 h. The
      leaflets were masked with agarose gel, and the aorta was treated with 1.25% (w/v)
      trypsin for 4 h at 37 degrees C. The trypsin and agarose were removed and the
      roots incubated with 0.1% (w/v) SDS in hypotonic buffer for 24 h. Fresh and
      treated circumferential and axial aortic specimens were subjected to uniaxial
      tensile testing, while intact porcine aortic roots were subjected to dilation and
      pulsatile flow testing. RESULTS: Decellularized aortic wall specimens
      demonstrated significantly decreased elastin phase slope and increased transition
      strain compared to the fresh control. However, the treatment did not impair
      tissue strength. Decellularized intact roots presented complete leaflet
      competence under systemic pressures, increased dilation and effective orifice
      areas, reduced pressure gradients, physiological leaflet kinematics and reduced
      leaflet deformation. CONCLUSION: The excellent leaflet kinematics and
      hydrodynamic performance of the decellularized roots, coupled with the excellent
      biomechanical characteristics of their aortic wall, form a promising platform for
      the creation of an acellular valve scaffold with adequate mechanical strength and
      functionality to accommodate dynamic cell repopulation in vitro or in vivo. This
      approach can be used for both allogeneic and xenogeneic tissue matrices.

PMID- 15974538
TI  - The current state of in-vivo pre-clinical animal models for heart valve
      evaluation.
AB  - For over 30 years, animal models have remained a central critical component in
      the pre-clinical safety evaluation of prosthetic heart valves developed for use
      in humans. Though many advances have been made in valve design, no ideal
      replacement prosthesis has yet been developed. As a result, valve manufacturers
      continue to address issues relating to thrombogenicity, structural integrity,
      fluid dynamics and calcification in their designs. Many animal models have been
      developed to examine these issues, including dog, pig, calf and sheep, yet no
      standard model has been accepted. Recently, the International Standard
      Organization has provided guidelines in document 5840 to address cardiovascular
      implants. The aim of this report is to provide a summary of the current state of
      pre-clinical valve evaluation in animals. Changes in ISO 5840 will be addressed
      that have occurred between 1998 and the present date, and the role of current
      available animal models. The aim also is to provide rational guidance in the
      selection of appropriate animal models to match the purpose of valve implantation
      studies.

PMID- 15974539
TI  - Clinical and hemodynamic performance of the 19-mm medtronic mosaic bioprosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: The Medtronic Mosaic valve (MMV) is a latest
      generation supra-annular stented porcine valve, which combines a low-profile
      stent, leaflet fixation at zero pressure in a predilated aortic root, and amino
      oleic acid anti-mineralization treatment for improved hemodynamics and
      durability. A study was conducted to evaluate the clinical and hemodynamic
      performances of the MMV in patients with a small aortic root (19 mm aortic
      annulus). METHODS: Between 1998 and 2004, 81 consecutive patients (69 females, 12
      males; mean age 78.0 +/- 5.5 years) underwent aortic valve replacement using the
      19-mm MMV. Concomitant coronary artery bypass grafting was performed in 28
      patients (29.2%), and mitral valve surgery in one patient (1.2%). RESULTS: The 30
      day mortality rate was 9.9% (eight deaths). Postoperative actuarial survival
      estimates were 90.1 +/- 3.3%, 78.5 +/- 4.6% and 69.1 +/- 5.5% at one month, one
      year and two years, respectively. After a mean follow up of 2.7 +/- 1.9 years, no
      cases of structural dysfunction, non-structural dysfunction or valve thrombosis
      were noted. Four ischemic cerebral complications (2.0% per patient-year (pt-yr)),
      five bleeding complications (2.0%/pt-yr) and two prosthetic valve infections
      (1.0%/pt-yr) were observed. No reoperation on a MMV was performed.
      Postoperatively, the mean systolic gradient was 23.4 +/- 7.0 mmHg, and the
      effective orifice area (EOA) 1.06 +/- 0.33 cm2. Valve prosthesis-patient mismatch
      (VP-PM) was moderate (indexed EOA > 0.65 cm2/m2 and < or = 0.85 cm2/m2) in 40
      patients (49.4%), and severe (indexed EOA < or = 0.65 cm2/m2) in 41 (50.6%).
      CONCLUSION: Although providing acceptable clinical results, implantation of the
      19-mm MMV resulted in a high incidence of postoperative VP-PM. Hence, this valve
      should be reserved for patients in whom the projected indexed EOA calculated
      preoperatively is deemed acceptable, given the patient's clinical condition.

PMID- 15974540
TI  - 'Under-12s have sex one night and play with barbie dolls the next'.

PMID- 15974541
TI  - Under surveillance.
AB  - This article outlines the importance of surveillance of healthcare-associated
      infections (HAIs), and argues for extension of mandatory surveillance.

PMID- 15974542
TI  - Stuck for choice.

PMID- 15974543
TI  - A private matter.

PMID- 15974544
TI  - Desperate measures.

PMID- 15974545
TI  - Conquer the fear.

PMID- 15974546
TI  - Mentoring learners in practice: no. 10. Demonstrating nursing skills.

PMID- 15974547
TI  - The use of expert practice to explore reflection.
AB  - This article describes an experience, drawn from clinical practice, which has
      been used to expand personal knowledge and enable self-reflection. Johns' (1995)
      model of structured reflection provides an analysis of the practice experience.
      Carper's (1978) four ways of knowing is used to discuss personal learning and
      development.

PMID- 15974548
TI  - Unsupervised medication administration by nursing students.
AB  - Nursing students need sufficient practical experience to qualify with the full
      range of skills required for effective practice. One area of nursing practice
      that needs to be addressed is the practical experience given to nursing students
      in the administration of medication. It is recommended that universities and NHS
      trusts review their policies to allow final year students to administer
      medication unsupervised to gain the necessary skills and experience to become
      competent administrators of medication. A contractual arrangement between the
      university and NHS trust for each student is proposed to ensure that nursing
      students are deemed competent and safe to administer medication unsupervised.

PMID- 15974550
TI  - Reading the signs.

PMID- 15974549
TI  - Providing a travel health service in primary care.
AB  - A dedicated travel health service in primary care has many benefits for practice
      patients, as well as being satisfying and rewarding for the health professionals
      involved. This article discusses the practical and financial aspects of setting
      up and running a travel health clinic. The importance of thorough planning,
      meticulous execution of processes and efficient delivery of the service, using
      protocols, patient group directions and guidelines, is emphasised.

PMID- 15974551
TI  - Someone to understand.

PMID- 15974552
TI  - 'Beyond my wildest dreams'.

PMID- 15974553
TI  - When it all goes wrong.

PMID- 15974554
TI  - A qualitative review of studies of diabetes preventive care among minority
      patients in the United States, 1993-2003.
AB  - OBJECTIVE: To review existing data to determine whether ethnic disparities exist
      for diabetes-related preventive care among adults in the United States. STUDY
      DESIGN: Literature review. METHODS: We identified diabetes-related studies
      published between 1993 and 2003, using a reproducible search strategy. Studies
      were selected for review if there were ethnic comparisons or if data on a
      specific ethnic minority were reported. From these studies, we extracted data on
      commonly accepted diabetes-related preventive-care measures (testing for
      glycemia, eye examinations, foot examinations, lipid profile, influenza
      vaccination, nephropathy assessment, smoking-cessation counseling). The sources
      were US healthcare facilities, national survey samples, Veterans Affairs
      facilities, Medicare databases, and managed care data. RESULTS: Thirty-six
      studies met our search criteria. Data were extracted on glycemia testing (15
      studies), eye examination rates (27 studies), foot examination rates (18
      studies), lipid-profile assessment (15 studies), percentage of patients receiving
      influenza vaccinations (8 studies), nephropathy assessment (7 studies), and
      counseling referrals for smoking cessation (4 studies). The majority of the data
      indicated that the rates of diabetes monitoring are generally low regardless of
      the population being studied. The major ethnic differences reported were lower
      rates of eye examination, influenza vaccination, and lipid-profile testing among
      Hispanics and African Americans than among non-Hispanic whites. CONCLUSIONS:
      Despite the availability of evidence-based guidelines, rates of diabetes
      preventive care are low, particularly for some measures in ethnic minority
      groups. Additional data are needed to further elucidate these disparities.

PMID- 15974555
TI  - Improving asthma treatment in a managed care population.
AB  - OBJECTIVE: To identify and educate members of ConnectiCare, Inc & Affiliates, a
      regional managed care organization, who were not using asthma medications as
      recommended by the National Heart, Lung, and Blood Institute, by means of a nurse
      administered 6-month telephonic case management intervention called the Asthma
      Treatment Awareness Project. STUDY DESIGN: A randomized controlled design was
      used to evaluate intervention and control groups. Self-selected members who opted
      in, opted out, or did not respond to an invitation to participate were included
      in the analysis. METHODS: Changes in asthma medication use, physician office
      visits, emergency department visits, hospitalizations, and quality of life were
      measured. A change in asthma medication use was measured using an asthma
      medication index ranging from 0 to 1.00, with a higher score indicating a better
      prescribing pattern. RESULTS: There was significant improvement in asthma
      medication use for all groups, but the asthma medication index increase of 0.176
      for the intervention group was nearly 2 times the 0.091 increase for the control
      group. This difference remained significant (P = .04) after using analysis of
      variance to control for age and the preintervention asthma medication index.
      There was also a significant increase in overall quality of life for the
      intervention group (P = .04) but not for the control group. CONCLUSION:
      Individualized telephonic case management from a specially trained registered
      nurse may be effective in improving asthma medication use and quality of life in
      subjects that do not use asthma medications according to National Heart, Lung,
      and Blood Institute guidelines.

PMID- 15974556
TI  - The effect of the Rx-to-OTC switch of loratadine and changes in prescription drug
      benefits on utilization and cost of therapy.
AB  - BACKGROUND: Numerous prescription products have become available over the counter
      (OTC) in recent years. Previous simulation models have shown the Rx-to-OTC switch
      of loratadine to be cost effective. OBJECTIVE: To empirically assess the overall
      effect of the Rx-to-OTC switch of loratadine and the specific effect of different
      pharmacy benefit structures on prescription drug utilization and cost among
      different plan sponsors. METHODS: Data from a national pharmacy benefit
      management organization covering lives throughout the United States were used.
      The analysis included a comparison of the before and after change in prescription
      utilization and cost for plan sponsors that instituted 1 of 3 second-generation
      antihistamine (SGA) benefit responses: made no change, moved SGAs to the third
      tier, or restricted SGA benefits through a requirement for prior authorization.
      Multivariate regression analysis was used to control for differences across the
      study groups. RESULTS: There was a substantial decrease in utilization and cost
      of all prescription drugs and combinations of drug classes. Patients with
      allergic rhinitis facing restricted prescription benefits for SGAs did not appear
      to increase utilization of other allergic rhinitis medications or other
      medications used to treat comorbid conditions such as asthma, sinusitis, and
      otitis media. CONCLUSIONS: Utilization and cost decreased substantially for all
      types of medications and all pharmacy benefit structures. Future studies need to
      examine the effect of the Rx-to-OTC switch of loratadine and resultant
      prescription benefit policies on medical utilization and OTC antihistamine
      utilization.

PMID- 15974557
TI  - Financial interests, detailed description of methods, and use of randomized
      design in a real-world setting.

PMID- 15974558
TI  - Current evidence for the use of emerging radiologic technologies for disease
      screening.
AB  - Recent technologic advances in the field of radiology have resulted in the
      availability of several new tests with potential applications for disease
      screening. Presently, these tests are being marketed directly to patients as
      noninvasive means to provide peace of mind that they are disease free. Such
      assurance is appealing to many individuals, and some are willing to spend up to
      1500 dollars to choose from a menu of available diagnostic options. Given that a
      physician's referral is unnecessary, many healthcare providers are unaware that
      such testing has taken place until their patients present to them with abnormal
      test results. In this review, we examine the evidence supporting the use of
      electron beam computed tomography for coronary artery disease screening, spiral
      computed tomography of the chest for lung cancer screening, computed tomographic
      colonography for colon cancer screening, and total-body computed tomography for
      general screening. Although some of these modalities show promise for the future,
      there is insufficient evidence to support the use of any of these testing methods
      for secondary prevention. The potential for harm associated with false-positive
      test results, false-negative test results, undue anxiety, and radiation exposure
      exists but requires further study to quantify actual risk.

PMID- 15974559
TI  - Is patient HMO insurance or physician HMO participation related to racial
      disparities in primary care?
AB  - OBJECTIVE: To examine the relationship between racial disparities in common
      primary care procedures and patient HMO membership and physician level of HMO
      participation. DESIGN: Cross-sectional analysis. METHODS: Data were obtained from
      a nationally representative sample of primary care office visits documented in
      the National Ambulatory Medical Care Survey for 1985, 1989-1992, and 1997-2000.
      Patient HMO membership was assessed based on reports by primary care physicians
      (defined as family physicians/general practitioners, internists, or obstetrician
      gynecologists). Physician HMO participation was assessed based on the proportion
      of the physician's patients who were in an HMO. Patient characteristics (age,
      sex, race, insurance, diagnoses) and office procedures or interventions were
      determined by examining the physician report. Patients were adults aged 19 years
      or older. RESULTS: In adjusted analyses, African Americans, compared with whites,
      had lower odds of receiving a Pap test (adjusted odds ratio [AORI = 0.76; 95%
      confidence interval [CI] = 0.65, .90), a rectal exam (AOR = 0.67; 95% CI = 0.54,
      0.84), smoking cessation advice (AOR = 0.72; 95% CI = 0.58, 0.91), and mental
      health advice (AOR = 0.46; 95% CI = 0.29, 0.72), but had higher odds of receiving
      advice on diet and weight, and a follow-up appointment. Notably, there were no
      significant interactions between either patient HMO membership or physician level
      of HMO participation, patient race, and receipt of primary care services.
      CONCLUSION: Neither patient HMO membership nor physician level of HMO
      participation is substantially associated with racial disparities in primary
      care.

PMID- 15974560
TI  - A "one-day survey": as a reliable estimation of the potential recruitment for
      proton- and carbon- ion therapy in France.
AB  - To estimate the real figure of the potential patient recruitment for
      hadrontherapy we carried out a survey directly in 5 radiation therapy departments
      of the East of France as a "one-day survey". The results presented account for 77
      cases of potential indications among 532 evaluated medical records.

PMID- 15974561
TI  - Proceedings of the European Workshop on MR and CT Imaging of the Heart. October,
      2004. Seville, Spain.

PMID- 15974562
TI  - Proceedings of the European Association for Cardio-Thoracic Surgery Symposium for
      the Future of Cardiac Surgery. July 1-2, 2004. Frankfurt, Germany.

PMID- 15974563
TI  - The incidence of upper gastrointestinal adverse events in clinical trials of
      etoricoxib vs. non-selective NSAIDs: an updated combined analysis.
AB  - OBJECTIVE: In spite of numerous studies demonstrating the serious
      gastrointestinal (GI) toxicity associated with non-selective non-steroidal anti
      inflammatory drugs (NSAIDs), many patients at high GI risk continue to receive
      prescriptions for these drugs, often without gastroprotective agents. Etoricoxib,
      a COX-2 specific inhibitor, was developed to provide similar efficacy and less GI
      toxicity than non-selective NSAIDs. We compared the incidence of upper GI
      Perforations, symptomatic gastroduodenal Ulcers, and upper GI Bleeding (PUBs) in
      a combined analysis of all randomized, double-blind, clinical trials of chronic
      treatment with etoricoxib versus NSAIDs completed by June 2003. RESEARCH DESIGN
      AND METHODS: Data for 5441 individual subjects with osteoarthritis, rheumatoid
      arthritis, or ankylosing spondylitis were pooled from all 10 multinational
      etoricoxib trials completed by June 2003. Information on suspected PUBs was
      prospectively collected in all protocols, and all investigator-reported PUBs were
      judged by a blinded, external adjudication committee using pre-specified
      criteria. PUBs were analyzed using COX proportional hazards models using terms
      for treatment and known PUB risk factors. MAIN OUTCOME MEASURE: The incidence of
      confirmed PUBs among patients treated with etoricoxib 60 mg, 90 mg, or 120 mg
      (combined N=3226) was compared to that among patients treated with ibuprofen,
      diclofenac, or naproxen (combined N=2215). RESULTS: The incidence of PUBs over
      44.3 months was significantly lower with etoricoxib vs. NSAIDs [cumulative
      incidence 1.24% vs. 2.48%, p < 0.001; rate/100 patient-years 1.00 vs. 2.47;
      relative risk 0.48, 95% Confidence Interval (CI) 0.32, 0.73]. Results of analysis
      of events occurring during the first year of treatment and subgroup analyses were
      consistent with the primary result. CONCLUSIONS: Treatment with etoricoxib was
      associated with a significantly lower incidence of PUBs than was treatment with
      non-selective NSAIDs. The difference was consistent in subgroups of patients
      defined by a variety of known risk factors.

PMID- 15974564
TI  - Visualization of protoplast fusion and quantitation of recombination in fused
      protoplasts of auxotrophic strains of Escherichia coli.
AB  - Protoplast fusion has been used to combine genes from different organisms to
      create strains with desired properties. A recently developed variant on this
      approach, genome shuffling, involves generation of a genetically heterogeneous
      population of a single organism, followed by recursive protoplast fusion to allow
      recombination of mutations within the fused protoplasts. These are powerful
      techniques for engineering of microbial strains for desirable industrial
      properties. However, there is a prevailing opinion that it will be difficult to
      use these methods for engineering of Gram-negative bacteria because the outer
      membrane makes protoplast fusion more difficult. Here we describe the successful
      use of protoplast fusion in Escherichia coli. Using two auxotrophic strains of E.
      coli, we obtained prototrophic strains by recombination in fused protoplasts at
      frequencies of 0.05-0.7% based on the number of protoplasts subjected to fusion.
      This frequency is three-four orders of magnitude better than those previously
      reported for recombination in fused protoplasts of Gram-negative bacteria such as
      E. coli and Providencia alcalifaciens.

PMID- 15974565
TI  - Incontinence care: managing both patient and cost.

PMID- 15974567
TI  - Compensatory load redistribution of horses with induced weight-bearing forelimb
      lameness trotting on a treadmill.
AB  - The study was performed to obtain a detailed insight into the load and time
      shifting mechanisms of horses with unilateral weight-bearing forelimb lameness.
      Reversible lameness was induced in 11 clinically sound horses by applying a solar
      pressure model. Three degrees of lameness (subtle, mild and moderate) were
      induced and compared with sound control measurements. Vertical ground reaction
      force-time histories of all four limbs were recorded simultaneously on an
      instrumented treadmill. Four compensatory mechanisms could be identified that
      served to reduce structural stress, i.e. peak vertical force on the affected
      limb: (1) with increasing lameness, horses reduced the total vertical impulse per
      stride; (2) the diagonal impulse decreased selectively in the lame diagonal; (3)
      the impulse was shifted within the lame diagonal to the hindlimb and in the sound
      diagonal to the forelimb; (4) the rate of loading and the peak forces were
      reduced by prolonging the stance duration. Except in the diagonal hindlimb, where
      peak vertical forces increased slightly in the moderate lameness condition, no
      equivalent compensatory overload situation was observed in the other limbs.
      Specific force and time information of all four limbs allow the unequivocal
      identification of the affected limb.

PMID- 15974568
TI  - Searching techniques for databases of two- and three-dimensional chemical
      structures.

PMID- 15974569
TI  - Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives
      in three animal models of pain.
AB  - Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor
      antagonists, exhibited high GluR5 receptor affinity over other glutamate
      receptors. Their ester prodrugs 6 and 8 were orally active in three models of
      pain: reversal of formalin-induced paw licking, carrageenan-induced thermal
      hyperalgesia, and capsaicin-induced mechanical hyperalgesia.

PMID- 15974570
TI  - Ligand binding analysis for human alpha5beta1 integrin: strategies for designing
      new alpha5beta1 integrin antagonists.
AB  - We report a three-dimensional model of the alpha5beta1 integrin headgroup bound
      to the most potent and selective ligand (SJ749) known to date. The model was
      built using the comparative protein modeling method, and it is consistent with
      experimental data. From this study, we identified two potentially important
      regions in the alpha5beta1 receptor that are peculiar to this integrin and might
      be worth considering for drug targeting.

PMID- 15974571
TI  - 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer
      cyclin-dependent kinase inhibitors: synthesis and evaluation of biological
      activities.
AB  - A series of 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogues were synthesized as
      cyclin-dependent kinase (CDK) inhibitors. These compounds showed potent and
      selective CDK1 and CDK2 inhibitory activities and inhibited in vitro cellular
      proliferation in various human tumor cells. Representative compound 3b
      demonstrated in vivo efficacy in a human melanoma A375 xenograft model in nude
      mice.

PMID- 15974572
TI  - Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90
      discovered through structure-based design.
AB  - The crystal structure of a previously reported screening hit 1 (CCT018159) bound
      to the N terminal domain of molecular chaperone Hsp90 has been used to design 5
      amide analogues. These exhibit enhanced potency against the target in binding and
      functional assays with accompanying appropriate cellular pharmacodynamic changes.
      Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

PMID- 15974573
TI  - A three-dimensional pharmacophore model for 5-hydroxytryptamine6 (5-HT6) receptor
      antagonists.
AB  - Forty-five structurally diverse 5-hydroxytryptamine(6) receptor (5-HT(6)R)
      antagonists were selected to develop a 3D pharmacophore model with the Catalyst
      software. The structural features for antagonism at this receptor are a positive
      ionizable atom interacting with Asp(3.32), a hydrogen bond acceptor group
      interacting with Ser(5.43) and Asn(6.55), a hydrophobic site interacting with
      residues in a hydrophobic pocket between transmembranes 3, 4, and 5, and an
      aromatic-ring hydrophobic site interacting with Phe(6.52).

PMID- 15974574
TI  - Design, synthesis, and biological activities of pyrrolylethanoneamine
      derivatives, a novel class of monoamine oxidases inhibitors.
AB  - Pyrrolylethanoneamines 1-12, 18-23 and related amino alcohols 13-15, 24-27 were
      synthesized and tested against monoamine oxidases A and B (MAO-A and MAO-B)
      enzymes. In general, aminoketones 1-12, 18-23 were found to be potent and
      selective MAO-A inhibitors. In particular, 18 was more potent and selective
      against the MAO-A isoenzyme than reference drugs. Interestingly, amino alcohol 25
      selectively inhibited MAO-B enzyme and could be a lead compound for designing
      more potent and selective MAO-B inhibitors.

PMID- 15974575
TI  - Peptoid-peptide hybrids as potent novel melanocortin receptor ligands.
AB  - All possible peptoid-peptide hybrids of an MC4 receptor agonist were synthesized
      and investigated on cells expressing different melanocortin (MC) receptor
      subtypes and for rat grooming behavior. In general, receptor selectivity remained
      while affinity and potency were decreased. The length of the functional group of
      Trp was more important for MC3 and MC5 than for MC4 receptor binding. In general,
      the potency of the peptoid-peptide hybrids to increase rat excessive grooming
      behavior correlated well with MC4 receptor pharmacology.

PMID- 15974576
TI  - Synthesis and ocular effects of imidazole nitrolic acids.
AB  - Novel 1-R-imidazole-2-nitrolic acids and 1-R-imidazole-5-nitrolic acids (R: H,
      Me, Bn) were synthesized from oximes by treatment with a mixture of fuming nitric
      acid and acetic acid. The effects of these potential nitric oxide-donating
      compounds were tested on ocular variables such as intraocular pressure and
      formation of cyclic guanosine-3,5'-monophosphate in the incubation of porcine
      iris-ciliary body.

PMID- 15974577
TI  - Functionalized pyrrolidines inhibit alpha-mannosidase activity and growth of
      human glioblastoma and melanoma cells.
AB  - New substituted pyrrolidine-3,4-diol derivatives were prepared from d-(-)- and l
      (+)-phenyl glycinol. The influence of the configuration and the substitution of
      the lateral side chain of these derivatives on the inhibition of 25 commercial
      glycosidases were determined. (2R,3R,4S)-2-({[(1R)-2-Hydroxy-1
      phenylethyl]amino}methyl)pyrrolidine-3,4-diol ((+)-7a) was a potent and selective
      inhibitor of jack bean alpha-mannosidase (K(i) = 135 nM). However, when evaluated
      on human tumor cells, 7a, and the reference compound swainsonine, did not
      efficiently inhibit the growth of glioblastoma cells. Further derivatization of
      the hydroxyl group with lipophilic groups to increase bioavailability improved
      their growth inhibitory properties for human glioblastoma and melanoma cells. In
      particular, the 4-bromobenzoyl derivative 26 demonstrated high efficacy for human
      tumor cells whereas primary human fibroblasts were less sensitive to 26.
      Therefore, functionalized pyrrolidines have the potential to inhibit the growth
      of tumor cells and display selectivity for tumor cells when compared to normal
      cells.

PMID- 15974578
TI  - Positional effect of chemical modifications on short interference RNA activity in
      mammalian cells.
AB  - A systematic study on the effect of 2'-sugar modifications (2'-F (2'-F-2'-deoxy
      nucleoside residues), 2'-O-Me (2'-O-methyl-nucleoside residues), and 2'-O-MOE [2'
      O-(2-methoxyethyl)]-nucleoside residues) in the antisense and sense strands of
      short interference RNA (siRNA) was performed in HeLa cells. The study of the
      antisense strand of siRNAs demonstrated that activity depends on the position of
      the modifications in the sequence. The siRNAs with modified ribonucleotides at
      the 5'-end of the antisense strand were less active relative to the 3'-modified
      ones. The 2'-F sugar was generally well-tolerated on the antisense strand,
      whereas the 2'-O-Me showed significant shift in activity depending on the
      position of modification. The 2'-O-MOE modification in the antisense strand
      resulted in less active siRNA constructs regardless of placement position in the
      construct. The incorporation of the modified residues, e.g., 2'-O-Me and 2'-O
      MOE, in the sense strand of siRNA did not show a strong positional preference.
      These results may provide guidelines to design effective and stable siRNAs for
      RNA interference mediated therapeutic applications.

PMID- 15974579
TI  - Synthesis, in vitro characterization, and radiolabeling of N,N-dimethyl-2-(2'
      amino-4'-substituted-phenylthio)benzylamines: potential candidates as selective
      serotonin transporter radioligands.
AB  - A series of N,N-dimethylated and N-monomethylated analogues of N,N-dimethyl-2-(2'
      amino-4'-iodophenylthio)benzylamine substituted at the 4'-phenyl position have
      been prepared and evaluated in vitro for serotonin transporter (SERT)
      selectivity. Several derivatives were prepared where the 4'-position was either
      unsubstituted 13 and 33a or substituted with methyl 14a and 33b, ethenyl 14b and
      34, ethyl 16 and 35, hydroxymethyl 20 and 41, hydroxyethyl 22, fluoroethyl 23,
      hydroxypropyl 27, and fluoropropyl 28. Competition binding in cells stably
      expressing the transfected human SERT, dopamine transporter (DAT), and
      norepinephrine transporter (NET) using [(3)H]citalopram, [(3)H]WIN 35,428 or
      [(125)I]RTI-55, and [(3)H]nisoxetine, respectively, demonstrated the following
      order of SERT affinity (K(i) (nM)): 14a (0.25) > 16 (0.49) > 20 (0.57) > 14b
      (1.12) > 13 (1.59) > 33b (1.94) = 35 (2.04) >> 23 (8.50) = 28 (8.55) > 41 (15.11)
      >> 22 (51) > 33a (83.43) > 27 (92). The K(i) values revealed that most of these
      derivatives displayed a high affinity for the SERT and a high selectivity over
      the DAT and NET. Moreover, substitution at the 4'-position of the dimethylated
      and monomethylated benzylamines differently influenced SERT binding: (i) the
      dimethylated benzylamines exhibited higher SERT affinity than the monomethylated
      ones, (ii) alkyl, alkenyl, or hydroxymethyl functions at the 4'-position afford
      compounds with high SERT affinity, and (iii) omega-hydroxy and fluoro-substituted
      ethyl and propyl groups at the 4'-position decrease the SERT affinity. From this
      series, the dimethylated derivatives 13, 14a, 14b, 16, and 20 were radiolabeled
      with carbon-11 and their log P(7.4) was calculated as a measure of their
      potential brain penetrance as positron emission tomography SERT imaging agents.

PMID- 15974580
TI  - Reversion of human Pgp-dependent multidrug resistance by new sesquiterpenes from
      Zinowiewia costaricensis.
AB  - In an intensive study of South American medicinal plants, herein we report the
      isolation, structure elucidation and biological activity of fourteen new and five
      known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia
      costaricensis (1-19). Their structures were determined by means of (1)H and (13)C
      NMR spectroscopic studies, including homonuclear and heteronuclear correlation
      experiments. The absolute configurations of the new compounds were determined by
      CD studies, chemical correlations or biogenetic grounds. All the natural
      compounds and derivative 20 have been tested on human MDR1-transfected NIH-3T3
      cells, to determine their ability to revert the multidrug resistance phenotype
      due to P-glycoprotein overexpression. Six compounds from this series (1, 8, 11,
      12, 13 and 14) showed similar effectiveness to the classical P-glycoprotein
      modulator verapamil when reversing resistance to daunorubicin, but it is up to
      sixteen times greater than that of verapamil when reversing resistance to
      vinblastine. The structure-activity relationships are discussed.

PMID- 15974581
TI  - First synthesis and evaluation of the inhibitory effects of aza analogues of TSAO
      on HIV-1 replication.
AB  - Aza TSAO-T derivatives bearing a dihydroisothiazole dioxide ring instead of an
      oxathiole dioxide ring at the C-3' position on the sugar moiety were prepared. We
      have synthesized four families of compounds depending on substitution at both N-3
      and N-2' '. Biological evaluation showed that these compounds are HIV-1(III(B))
      specific and potent reverse transcriptase inhibitors with EC(50) values between
      0.13 and 3.5 microM in cell culture.

PMID- 15974582
TI  - Synthesis and biological activity of nitronyl nitroxide containing peptides.
AB  - [1-(1',3'-Dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4
      yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1
      (1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl
      ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized.
      Judging from the results of electron spin resonance analysis, the newly
      synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated
      the characteristics of free radicals. The free radical scavenging activities of
      9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The
      thrombolysis effect of 9a, 9b, and 9cwas evaluated using an euglobulin clot lysis
      test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results
      indicated that these nitronyl nitroxide containing peptides possessed both free
      radical scavenging activity and thrombolytic activity.

PMID- 15974583
TI  - Studies on the apoptotic activity of natural and synthetic retinoids: discovery
      of a new class of synthetic terphenyls that potently support cell growth and
      inhibit apoptosis in neuronal and HL-60 cells.
AB  - New terphenyl derivatives have been synthesized and tested for their effect on
      cell survival in serum-free cultures. These compounds protected HL60 cells from
      death and supported their growth with an activity higher than that of the natural
      14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic
      activity on neuronal cells, proving them as possible candidates for the treatment
      of neurodegenerative and ischemic diseases.

PMID- 15974584
TI  - Synthesis and evaluation of (17alpha,20Z)-21-(4-substituted-phenyl)-19-norpregna
      1,3,5(10),20-tetraene-3,17beta-diols as ligands for the estrogen receptor-alpha
      hormone binding domain: comparison with 20E-isomers.
AB  - As part of our ongoing program to develop probes for the hormone binding domain
      of the estrogen receptor-alpha (ERalpha), we prepared and evaluated a series of
      17alpha,Z-(4-substituted-phenyl)vinyl estradiol derivatives. The results
      indicated that the relative binding affinities (RBAs) at 25 degrees C for the new
      compounds were significant (RBA = 9-57) although less than that of estradiol (RBA
      = 100) or of the parent unsubstituted phenylvinyl estradiol (RBA = 66). All of
      the Z-compounds were full agonists in the uterotrophic assay, indicating that the
      ligands formed estrogen-like complexes with the estrogen receptor-alpha hormone
      binding domain (ERalpha-HBD). Comparison of corresponding Z- and E-4-substituted
      phenylvinyl ligands complexed with the ERalpha-HBD indicated small but
      significant differences in binding modes that may account for the differing
      trends seen in the structure-activity relationships for the two series.

PMID- 15974585
TI  - 2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive
      CXCL8 inhibitors.
AB  - The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment
      of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by
      binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine
      receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was
      previously reported to be a potent and specific noncompetitive inhibitor of CXCL8
      induced human PMNs chemotaxis. We report here molecular modeling studies showing
      a putative interaction site of 1 in the TM region of CXCR1. The binding model was
      confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments.
      The molecular model driven medicinal chemistry optimization of 1 led to a new
      class of potent and specific inhibitors of CXCL8 biological activity. Among
      these, repertaxin (13) was selected as a clinical candidate drug for prevention
      of post-ischemia reperfusion injury.

PMID- 15974586
TI  - Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding
      and protein-ligand affinity.
AB  - We report the discovery, synthesis, and crystallographic binding mode of novel
      furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology
      target. These inhibitors are synthetically tractable and inhibit Chk1 by
      competing for its ATP site. A chronological account allows an objective
      comparison of modeled compound docking modes to the subsequently obtained crystal
      structures. The comparison provides insights regarding the interpretation of
      modeling results, in relationship to the multiple reasonable docking modes which
      may be obtained in a kinase-ATP site. The crystal structures were used to guide
      medicinal chemistry efforts. This led to a thorough characterization of a pair of
      ligand-protein complexes which differ by a single hydrogen bond. An analysis
      indicates that this hydrogen bond is expected to contribute a fraction of the 10
      fold change in binding affinity, adding a valuable observation to the debate
      about the energetic role of hydrogen bonding in molecular recognition.

PMID- 15974587
TI  - Quinic acid derivatives as sialyl Lewis(x)-mimicking selectin inhibitors: design,
      synthesis, and crystal structure in complex with E-selectin.
AB  - A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid
      derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal
      structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two
      hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide
      sLe(x). The X-ray structure, together with structure based computational methods,
      was used to design quinic acid based libraries that were synthesized and
      evaluated for their ability to block the interaction of sLex with P-selectin. A
      large number of analogues were prepared using solution-phase parallel synthesis.
      Selected compounds showed decrease in leukocyte rolling in the IVM mouse model.
      Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated
      good plasma exposure.

PMID- 15974588
TI  - A robust clustering method for chemical structures.
AB  - A clustering method based on finding the largest set of disconnected fragments
      that two chemical compounds have in common is shown to be able to group
      structures in a way that is ideally suited to medicinal chemistry programs. We
      describe how markedly improved results can be obtained by using a similarity
      metric that accounts not just for the size of the shared fragments but also on
      their relative arrangement in the two parent compounds. The use of a
      physiochemical atom typing scheme is also shown to provide significant
      contributions. Results from calculations using a test set consisting of actives
      from nine different important biological target proteins demonstrate the
      strengths of our clustering method and the advantages over other approaches that
      are widely used throughout the pharmaceutical industry.

PMID- 15974589
TI  - Pyrrolo[1,5]benzoxa(thia)zepines as a new class of potent apoptotic agents.
      Biological studies and identification of an intracellular location of their drug
      target.
AB  - We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic
      agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their
      potential as novel anticancer agents. The core structure of the apoptotic agent 6
      was investigated, and the SARs were expanded with the design and synthesis of
      several analogues. To define the apoptotic mechanism of the new compounds and the
      localization of their drug target, two analogues of 6 were designed and
      synthesized to delineate events leading to JNK activation. The cell-penetrating
      compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue,
      17, was incapable of inducing apoptosis or activating JNK. Plasma membrane
      permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting
      that the pyrrolo-1,5-benzoxazepine molecular target is intracellular.
      Interestingly, compound 6 displayed cytotoxic activity against a panel of human
      tumor cell lines but demonstrated negligible toxicity in vivo with no effect on
      the animals' hematology parameters.

PMID- 15974590
TI  - Novel 1-[2-(diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles as HIV-1 non
      nucleoside reverse transcriptase inhibitors. A structure-activity relationship
      investigation.
AB  - 1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles (DAMNIs) is a novel family
      of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at
      submicromolar concentration. Replacement of one phenyl ring of 1-[2
      (diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole (4) with heterocyclic rings,
      such as 2-thienyl or 3-pyridinyl, led to novel DAMNIs with increased activity. In
      HIV-1 WT cell-based assay the racemic 1-{2-[alpha-(thiophen-2
      yl)phenylmethoxy]ethyl}-2-methyl-5-nitroimidazole (7) (EC(50) = 0.03 microM)
      proved 5 times more active than compound 4. Docking experiments showed that the
      introduction of a chiral center would not affect the binding of both (R)-7 and
      (S)-7. The internal scoring function of the Autodock program calculated the same
      inhibition constant (K(i) = 7.9 nM) for the two enantiomers. Compounds 7 (ID(50)
      = 8.25 microM) were found more active than efavirenz (ID(50) = 25 microM) against
      the viral RT carrying the K103N mutation, suggesting for these compounds a
      potential use in efavirenz based anti-AIDS regimens.

PMID- 15974591
TI  - Pharmacophore, drug metabolism, and pharmacokinetics models on non-peptide AT1,
      AT2, and AT1/AT2 angiotensin II receptor antagonists.
AB  - About 20 non-peptide angiotensin II receptor antagonists are in various stages of
      clinical development. Different modeling approaches were used to predict the
      pharmacophoric requirements for AT(1) (angiotensin II receptor subtype 1)
      affinity. However, to our knowledge, none was used to predict both the
      selectivity toward AT(1) and AT(2) (angiotensin II receptor subtype 2) receptor
      subtypes. In this paper, partial least squares discriminant analysis is applied
      to derive the chemical features guiding AT(1) and AT(2) selectivity or mixed
      AT(1)/AT(2) receptor binding. The method can be used to modulate AT(1) versus
      AT(2) selectivity. Concerns that unopposed stimulation of the AT(2) receptor
      might produce adverse effects initiated a search for new balanced antagonists.
      Moreover, it can serve as a fast filtering procedure in database searches.
      Finally, some relevant pharmacokinetics and metabolic properties of the database
      of 53 compounds are calculated using the VolSurf and MetaSite software to allow
      the simultaneous characterization of pharmacodynamic and pharmacokinetics
      properties of the chemical space of angiotensin II receptor antagonists.

PMID- 15974592
TI  - Design and synthesis of potent inhibitors of plasmepsin I and II: X-ray crystal
      structure of inhibitor in complex with plasmepsin II.
AB  - New and potent inhibitors of the malarial aspartic proteases plasmepsin (Plm) I
      and II, from the deadliest malaria parasite Plasmodium falciparum, have been
      synthesized utilizing Suzuki coupling reactions on previously synthesized
      bromobenzyloxy-substituted statine-like inhibitors. The enzyme inhibition
      activity has been improved up to eight times by identifying P1 substituents that
      effectively bind to the continuous S1-S3 crevice of Plasmepsin I and II. By
      replacement of the bromo atom in the P1 p-bromobenzyloxy-substituted inhibitors
      with different aryl substituents, several inhibitors exhibiting K(i) values in
      the low nanomolar range for both Plm I and II have been identified. Some of these
      inhibitors are also effective in attenuating parasite growth in red blood cells,
      with the best inhibitors, compounds 2 and 4, displaying 70% and 83% inhibition,
      respectively, at a concentration of 5 microM. The design was partially guided by
      the X-ray crystal structure disclosed herein of the previously synthesized
      inhibitor 1 in complex with plasmepsin II.

PMID- 15974593
TI  - Three-dimensional quantitative structure-activity relationship analyses of beta
      lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide
      cotransporter PEPT1.
AB  - The utilization of the membrane transport protein PEPT1 as a drug delivery system
      is a promising strategy to enhance the oral bioavailability of drugs. Since very
      little is known about the substrate binding site of PEPT1, computational methods
      are a meaningful tool to gain a more detailed insight into the structural
      requirements for substrates. Three-dimensional quantitative structure-activity
      relationship (3D-QSAR) studies using the comparative molecular similarity indices
      analysis (CoMSIA) method were performed on a training set of 98 compounds.
      Affinity constants of beta-lactam antibiotics and tripeptides were determined at
      Caco-2 cells. A statistically reliable model of high predictive power was
      obtained (q(2) = 0.828, r(2) = 0.937). The results derived from CoMSIA were
      graphically interpreted using different field contribution maps. We identified
      those regions which are crucial for the interaction between peptidomimetics and
      PEPT1. The new 3D-QSAR model was used to design a new druglike compound mimicking
      a dipeptide. The predicted K(i) value was confirmed experimentally.

PMID- 15974594
TI  - Design, synthesis, and antifolate activity of new analogues of piritrexim and
      other diaminopyrimidine dihydrofolate reductase inhibitors with omega
      carboxyalkoxy or omega-carboxy-1-alkynyl substitution in the side chain.
AB  - As part of a search for dihydrofolate reductase (DHFR) inhibitors combining the
      high potency of piritrexim (PTX) with the high antiparasitic vs mammalian
      selectivity of trimethoprim (TMP), the heretofore undescribed 2,4-diamino-6
      (2',5'-disubstituted benzyl)pyrido[2,3-d]pyrimidines 6-14 with O-(omega
      carboxyalkyl) or omega-carboxy-1-alkynyl groups on the benzyl moiety were
      synthesized and tested against Pneumocystis carinii, Toxoplasma gondii, and
      Mycobacterium avium DHFR vs rat DHFR. Three N-(2,4-diaminopteridin-6-yl)methyl)
      2'-(omega-carboxy-1-alkynyl)dibenz[b,f]azepines (19-21) were also synthesized and
      tested. The pyridopyrimidine with the best combination of potency and selectivity
      was 2,4-diamino-5-methyl-6-[2'-(5-carboxy-1-butynyl)-5'-methoxy]benzyl]pyrimidine
      (13), with an IC(50) value of 0.65 nM against P. carinii DHFR, 0.57 nM against M.
      avium DHFR, and 55 nM against rat DHFR. The potency of 13 against P. carinii DHFR
      was 20-fold greater than that of PTX (IC(50) = 13 nM), and its selectivity index
      (SI) relative to rat DHFR was 85, whereas PTX was nonselective. The activity of
      13 against P. carinii DHFR was 20 000 times greater than that of TMP, with an SI
      of 96, whereas that of TMP was only 14. However 13 was no more potent than PTX
      against M. avium DHFR, and its SI was no better than that of TMP. Molecular
      modeling dynamics studies using compounds 10 and 13 indicated a slight binding
      preference for the latter, in qualitative agreement with the IC(50) data. Among
      the pteridines, the most potent against P. carinii DHFR and M. avium DHFR was the
      2'-(5-carboxy-1-butynyl)dibenz[b,f]azepinyl derivative 20 (IC(50) = 2.9 nM),
      whereas the most selective was the 2'-(5-carboxy-1-pentynyl) analogue 21, with SI
      values of >100 against both P. carinii and M. avium DHFR relative to rat DHFR.
      The final compound, 2,4-diamino-5-[3'-(4-carboxy-1-butynyl)-4'-bromo-5'
      methoxybenzyl]pyrimidine (22), was both potent and selective against M. avium
      DHFR (IC(50) = 0.47 nM, SI = 1300) but was not potent or selective against either
      P. carinii or T. gondii DHFR.

PMID- 15974595
TI  - Unveiling the full potential of flexible receptor docking using multiple
      crystallographic structures.
AB  - One of the current challenges in docking studies is the inclusion of receptor
      flexibility. This is crucial because the binding sites of many therapeutic
      targets sample a wide range of conformational states, which has major
      consequences on molecular recognition. In this paper, we make use of very large
      sets of X-ray structures of cyclin dependent kinase 2 (CDK2) and heat shock
      protein 90 (HSP90) to assess the performance of flexible receptor docking in
      binding-mode prediction and virtual screening experiments. Flexible receptor
      docking performs much better than rigid receptor docking in the former
      application. Regarding the latter, we observe a significant improvement in the
      prediction of binding affinities, but owing to an increase in the number of false
      positives, this is not translated into better hit rates. A simple scoring scheme
      to correct this limitation is presented. More importantly, pitfalls inherent to
      flexible receptor docking have been identified and guidelines are presented to
      avoid them.

PMID- 15974596
TI  - Cholinesterase inhibitors: xanthostigmine derivatives blocking the
      acetylcholinesterase-induced beta-amyloid aggregation.
AB  - In continuing research that led us to identify a new class of carbamate
      derivatives acting as potent (Rampa et al. J. Med. Chem. 1998, 41, 3976) and long
      lasting (Rampa et al. J. Med. Chem. 2001, 44, 3810) acetylcholinesterase (AChE)
      inhibitors, we obtained some analogues able to simultaneously block both the
      catalytic and the beta-amyloid (Abeta) proaggregatory activities of AChE. The key
      feature of these derivatives is a 2-arylidenebenzocycloalkanone moiety that
      provides the ability to bind at the AChE peripheral site responsible for
      promoting the Abeta aggregation. The new carbamates were tested in vitro for the
      inhibition of both cholinesterases and also for the ability to prevent the AChE
      induced Abeta aggregation. All of the compounds had AChE IC(50) values in the
      nanomolar range and showed the ability to block the AChE-induced Abeta
      aggregation, thus supporting the feasibility of this new strategy in the search
      of compounds for the treatment of Alzheimer's disease.

PMID- 15974597
TI  - Design and synthesis of alpha-aryloxyphenylacetic acid derivatives: a novel class
      of PPARalpha/gamma dual agonists with potent antihyperglycemic and lipid
      modulating activity.
AB  - The synthesis and structure-activity relationships of novel series of alpha
      aryloxyphenylacetic acids as PPARalpha/gamma dual agonists are reported. The
      initial search for surrogates of the ester group in the screen lead led first to
      the optimization of a subseries with a ketone moiety. Further efforts to modify
      the ketone subseries led to the design and synthesis of two new subseries
      containing fused heterocyclic ring systems. All these analogues were
      characterized by their "super" PPARalpha agonist activity and weak or partial
      agonist activity on PPARgamma in PPAR-GAL4 transactivation assays despite their
      similar binding affinities for both receptors. The cocrystal structures of
      compounds 7 and rosiglitazone with PPARgamma-LBD were compared, and significant
      differences were found in their interactions with the receptor. Select analogues
      in each subseries were further evaluated for in vivo efficacy. They all showed
      excellent anti-hyperglycemic efficacy in a db/db mouse model and hypolipidemic
      activity in hamster and dog models without provoking the typical PPARgamma
      associated side effects in the rat tolerability assay.

PMID- 15974599
TI  - A new synthetic agent with potent but selective cytotoxic activity against
      cancer.
AB  - The synthesis of novel unsymmetrical bifunctional antitumor agents was
      accomplished by linking an imidazoacridone moiety to another polycyclic
      heteroaromatic moiety via linkers of various length and rigidity. These compounds
      bind to cellular DNA, but it is hypothesized that biological effects become
      manifested when the drug-DNA complexes interact with critical DNA binding
      proteins that are involved in repair and transcription. The most promising
      compound of the series, 4ad (WMC79), consists of an imidazoacridone linked to a 3
      nitronaphthalimide moiety via a 1,4-dipropanopiperazine linker. It was found to
      be potently, but selectively, cytotoxic against colon cancers (GI(50) = 0.5 nM,
      LC(50) = 32 nM) and leukemias (GI(50) = 3.5 nM, LC(50) = 33 nM). Compound 4ad,
      which appears to be a candidate for further development as an anticancer drug,
      kills sensitive cells by induction of apoptosis. It also showed significant in
      vivo activity against HCT-116 colon cancer xenografts in nude mice. Other
      compounds in the series also exhibited antitumor properties, but they were
      significantly lower than that of 4ad.

PMID- 15974598
TI  - Discovery of potent anilide inhibitors against the severe acute respiratory
      syndrome 3CL protease.
AB  - A diversified library of peptide anilides was prepared, and their inhibition
      activities against the SARS-CoV 3CL protease were examined by a fluorogenic
      tetradecapeptide substrate. The most potent inhibitor is an anilide derived from
      2-chloro-4-nitroaniline, l-phenylalanine and 4-(dimethylamino)benzoic acid. This
      anilide is a competitive inhibitor of the SARS-CoV 3CL protease with K(i) = 0.03
      muM. The molecular docking experiment indicates that the P1 residue of this
      anilide inhibitor is distant from the nucleophilic SH of Cys145 in the active
      site.

PMID- 15974600
TI  - Modeling of purine derivatives transport across cell membranes based on their
      partition coefficient determination and quantum chemical calculations.
AB  - Mercaptopurine (6-MP), thioguanine (6-TG), and azathioprine (AZA) are purine
      antimetabolites introduced as anticancer or immunosuppressive drugs decades ago.
      Methylated AZA, called MAZA, is among the investigational drugs. The present
      study compares MAZA to the widely recognized drugs AZA, 6-MP, and 6-TG with
      respect to the ability of being transported across cell membranes. The obtained
      octanol/water phases partition coefficients and results of quantum chemical
      calculations predict the following sequence of hydrophobicity: MAZA > AZA > 6-TG
      > 6-MP.

PMID- 15974602
TI  - Anti-Helicobacter pylori compounds from Santalum album.
AB  - Six new sesquiterpenes, (Z)-2beta-hydroxy-14-hydro-beta-santalol (1), (Z)-2alpha
      hydroxy-albumol (2), 2R-(Z)-campherene-2,13-diol (3), (Z)-campherene-2beta,13
      diol (4), (Z)-7-hydroxynuciferol (5), and (Z)-1beta-hydroxy-2-hydrolanceol (6),
      together with five known compounds, (Z)-alpha-santalol (7), (Z)-beta-santalol
      (8), (Z)-lanceol (9), alpha-santaldiol (10), and beta-santaldiol (11), were
      isolated from Santalum album, by using bioassay-guided fractionation for
      Helicobacter pylori. The structures were determined by extensive NMR studies. The
      absolute configuration of compound 3 was determined by a modified Mosher method.
      The crude extracts as well as the isolated compounds showed antibacterial
      activity against H. pylori. Especially, compounds 7 and 8 have strong anti-H.
      pylori activities against a clarithromycin-resistant strain (TS281) as well as
      other strains.

PMID- 15974603
TI  - Sesquiterpenes from the New Zealand Liverwort Lepidolaena hodgsoniae.
AB  - NMR studies have shown that seven new sesquiterpenoids, 3, 4, 5a, and 7-10,
      isolated from dried samples of the New Zealand liverwort Lepidolaena hodgsoniae
      have the same substituted cyclopentapyran ring system as the previously described
      insecticidal sesquiterpene diene hodgsonox (1), which has been reported only from
      this plant. In all but one compound, 10, the 1,1-disubstituted double bond of
      hodgsonox has migrated into an endocyclic position, but only two, 5a and 9, have
      the double bonds in conjugation. These seven new compounds represent a variety of
      different oxidation levels. Two of the new derivatives, 9 and 10, were isolated
      only from an aged sample and are presumably artifacts. The only other terpenoid
      isolated in significant quantity was (7R,10R)-calamenene (2).

PMID- 15974604
TI  - Saponins from the leaves of Mimusops laurifolia.
AB  - Fifteen new bidesmosidic triterpenoid saponins (1-15) were isolated from a
      methanol extract of the leaves of Mimusops laurifolia. Their structures were
      established using one- and two-dimensional NMR spectroscopy and mass spectrometry
      and determined to be bidesmosides of protobassic acid (2-4, 11, 12, and 15) and
      of 16alpha-hydroxyprotobassic acid (1, 5-10, 13, and 14).

PMID- 15974605
TI  - Mollisosides A, B1, and B2: minor triterpene glycosides from the New Zealand and
      South Australian sea cucumber Australostichopus mollis.
AB  - Three new monosulfated triterpene glycosides, mollisosides A (2), B(1) (3), and
      B(2) (4), have been isolated from the sea cucumber Australostichopus mollis.
      Their structures were determined by NMR and mass spectra. The presence of
      sulfated glycosides in sea cucumbers belonging to the family Stichopodidae is
      uncommon.

PMID- 15974606
TI  - Indole alkaloids and other constituents of Rauwolfia serpentina.
AB  - From the dried roots of Rauwolfia serpentina were isolated five new indole
      alkaloids, N(b)-methylajmaline (1), N(b)-methylisoajmaline (2), 3
      hydroxysarpagine (3), yohimbinic acid (4), isorauhimbinic acid (5), a new iridoid
      glucoside, 7-epiloganin (6), and a new sucrose derivative, 6'-O-(3,4,5
      trimethoxybenzoyl)glomeratose A (7), together with 20 known compounds. The
      structures of the new compounds were determined by spectroscopic and chemical
      means. The inhibitory activities of the selected alkaloids on topoisomerase I and
      II and their cytotoxicity against the human promyelocytic leukemia (HL-60) cell
      lines were assessed.

PMID- 15974607
TI  - Cytotoxic germacrane sesquiterpenes from the aerial parts of Santolina insularis.
AB  - Chemical investigation of Santolina insularis afforded 11 germacrane
      sesquiterpenes (1-11), four of which (2, 3, 10, and 11) are new. The
      stereostructures of these compounds have been established by a combination of
      spectroscopic techniques (mainly NMR), chemical transformations, and application
      of the modified Mosher method. Compounds 8 and 10 showed a potent and selective
      cytotoxic activity against the human colon carcinoma cell line.

PMID- 15974608
TI  - Neoflavonoids and related constituents from Nepalese propolis and their nitric
      oxide production inhibitory activity.
AB  - A methanolic extract of Nepalese propolis yielded 10 new open-chain neoflavonoids
      (1-10), a new chalcone (11), and eight previously reported compounds (12-19).
      Their structures were determined on the basis of spectroscopic data and chemical
      conversion. The isolated compounds other than 5, 8, and 16 showed dose-dependent
      inhibitory activities on nitric oxide production in lipopolysaccharide-activated
      macrophage-like J774.1 cells and were more active than a positive control, N(G)
      monomethyl-L-arginine (IC(50), 27.1 microM). The most potent activities, of 6 and
      7 (IC(50), 0.5 microM), were greater than another positive control, caffeic acid
      phenethyl ester (IC(50), 4.8 microM).

PMID- 15974610
TI  - Discovery of new natural products by application of X-hitting, a novel algorithm
      for automated comparison of full UV spectra, combined with structural
      determination by NMR spectroscopy.
AB  - X-hitting, a newly developed algorithm for automated comparison of UV data, has
      been used for the tracking of two novel spiro-quinazoline metabolites, lapatins A
      (1) and B (2), in a screening study targeting quinazolines. The structures of 1
      and 2 were elucidated by analysis of spectroscopic data, primarily 2D NMR.

PMID- 15974609
TI  - Sorbicillin analogues and related dimeric compounds from Penicillium notatum.
AB  - In our screening of microorganisms for new natural products, the fungus
      Penicillium notatum delivered further members of the sorbicillin family, namely,
      the sohirnones A [3, 1-(2,4-dihydroxy-5-methylphenyl)hex-4-en-1-one], B [4a, 1
      (2,4,5-trihydroxy-3,6-dimethylphenyl)hexa-2,4-dien-1-one], and C [5, 1-(2,4,5
      trihydroxy-3,6-dimethylphenyl)hex-4-en-1-one]. A stable tautomer of
      oxosorbicillinol (7) was characterized as 6, and the recently described 7
      deacetoxyyanuthone (8) was reisolated. The additionally isolated rezishanones A-D
      (12-13c) are the first natural Diels-Alder products of sorbicillinol (1) with
      dienophiles not related with 1. The monomers and dimers showed weak antibacterial
      activity, but were inactive against fungi and algae. The structures were
      determined by spectroscopic methods and by comparison of the NMR data with those
      of the structurally related 2',3'-dihydrosorbicillin (2) and, in the case of 4a,
      by transformation into the known sorrentanone (4b).

PMID- 15974611
TI  - Xanthone glycosides from Polygala tenuifolia and their conformational analyses.
AB  - Seven xanthone glycosides were isolated from the cortexes of Polygala tenuifolia,
      and their structures were identified as polygalaxanthones VIII-XI (1-4),
      sibiricoxanthone B (5), 7-O-methylmangiferin (6), and lancerin (7), on the basis
      of spectroscopic analyses. Compounds 1-4 are new xanthone glycosides, and
      compounds 4 and 5 exist as rotamers. To explain this phenomenon, conformational
      analyses were performed on compounds 4 and 5 and other compounds with similar
      skeletons that were isolated from P. tenuifolia.

PMID- 15974612
TI  - Polyoxygenated steroids from the gorgonian Isis hippuris.
AB  - Eleven new hippuristanols (1-4, 7-9, and 11-14), along with eight known
      metabolites (5, 6, 10, and 15-19), have been isolated from the gorgonian coral
      Isis hippuris. Single-crystal X-ray diffraction analyses supported the structure
      elucidation of known steroids 5 and 10. The absolute structures of hippuristanols
      were established by application of modified Mosher's method on 19. Compounds 14
      19 have been found to exhibit significant cytotoxicity against several cancer
      cell lines.

PMID- 15974613
TI  - Simplified isolation procedure and interconversion of the diastereomers of
      nepetalactone and nepetalactol.
AB  - Three nepetalactones were isolated from Nepeta racemosa (mussinii) by traditional
      methods. An improved method was developed to isolate nepetalactones from N.
      faassenii. An epimerization procedure was used to prepare the fourth 7S
      nepetalactone diastereomer. The cis-fused nepetalactols were prepared by
      reduction of the corresponding nepetalactones, while the trans-fused
      nepetalactols were unstable and found to undergo ring-opening reactions yielding
      iridodials. The characterizations and structural assignments by means of NMR
      agree with quantum chemical density functional calculations.

PMID- 15974614
TI  - Stereochemical heterogeneity in Verongid sponge metabolites. Absolute
      stereochemistry of (+)-fistularin-3 and (+)-11-epi-fistularin-3 by microscale
      LCMS-Marfey's analysis.
AB  - The absolute configurations of fistularin-3, 11-epi-fistularin-3, and a related
      bis-oxazolidinone were determined by microscale hydrolysis followed by
      derivatization with 1-fluoro-2,4-dinitrophenyl-5-l-alaninamide. Samples of
      fistularin-3 from Verongid marine sponges collected in the Great Barrier Reef
      (Australia), Baia de Todos os Santos (Brazil), and the Key Largo, Florida (USA)
      varied in configuration at C11, a phenomenon that may be attributed to the
      involvement of stereochemically promiscuous hydroxylase enzymes. Variability in
      C11 configuration in fistularin-3 samples may have been overlooked in previously
      reported encounters due to the similarity of spectroscopic properties of
      fistularin-3 and 11-epi-fistularin-3 and their coelution under chromatographic
      conditions. Stereochemical heterogeneity at C11 in fistularin-3 samples suggests
      a possibility of a native biotransformation of suitable precursor in Verongid
      sponges by their associated microbial flora.

PMID- 15974615
TI  - Triterpenoid saponin anthranilates from Albizia grandibracteata leaves ingested
      by primates in Uganda.
AB  - Three new oleanane-type triterpene saponins (1-3), named grandibracteosides A-C,
      were isolated from the methanolic extract of leaves of Albizia grandibracteata, a
      species consumed by primates in the Kibale National Park, Uganda. The structures
      of the saponins were established using 1D and 2D NMR experiments and mass
      spectrometry and confirmed by acid and alkaline hydrolysis. The crude extract and
      the pure compounds showed significant inhibitory activity against KB and MCF7
      tumoral cell lines in vitro. The compounds are glycosides of acacic acid acylated
      by an o-aminobenzoyl unit. This is the first report of such ester saponins in
      dicotyledonous plants. Studies of the primate diet may provide a useful method
      for finding naturally occurring compounds of medicinal significance.

PMID- 15974616
TI  - Antibiotic terpenoid chloro-dihydroquinones from a new marine actinomycete.
AB  - As part of our continuing interest in exploring the chemistry of actinomycete
      bacteria uniquely adapted for survival in ocean sediments, we encountered several
      new strains, which by 16S rDNA sequence-based phylogenetic analysis were
      recognized as members of a new genus (tentatively called MAR4) within the family
      Streptomycetaceae. We report here the isolation and structure elucidation of
      three new chlorinated dihydroquinones (1-3) and one previously reported analogue,
      4, from our strain CNQ-525, isolated from ocean sediments collected at a depth of
      152 m near La Jolla, California. The compounds formally possess new carbon
      skeletons, but are related to several previously reported metabolites of the
      napyradiomycin class. The structures of the new molecules, which possess
      significant antibiotic properties and cancer cell cytotoxicities, were assigned
      by comprehensive spectral measurements and by comparison with NMR and other
      spectral data from the antibiotic A80915C (5), the full stereostructure of which
      was recently assigned by X-ray diffraction methods.

PMID- 15974617
TI  - Cytotoxic constituents of the fruit body of Daedalea dickisii.
AB  - Three new lanostane triterpenoids (1, 7, 8) and five new lanostane triterpene
      glucosides (2-6) have been isolated from the fruit bodies of Daedalea dickinsii.
      Their structures were established primarily by NMR experiments, and their
      biological activity against HL-60 and HCT-15 cell lines was investigated.
      Compounds 3-6 induced internucleosomal DNA fragmentation characteristic of
      apoptotic cell death in the HL-60 cell line.

PMID- 15974619
TI  - Pseudopyronines A and B, alpha-pyrones produced by a marine Pseudomonas sp.
      F92S91, and evidence for the conversion of 4-hydroxy-alpha-pyrone to 3-furanone.
AB  - In our search for inhibitors of bacterial fatty acid biosynthesis, two new alpha
      pyrones, pseudopyronines A (1) and B (2), were isolated from a marine Pseudomonas
      sp. F92S91. The naturally occurring alpha-pyrones appeared to be unstable,
      evidenced by the conversion of pseudopyronine B into an oxidation product, 3
      furanone (3). Structural elucidations were made by spectroscopic analyses
      including 2D-NMR data.

PMID- 15974618
TI  - Sesquiterpenes from the red alga Laurencia tristicha.
AB  - Seven new sesquiterpenes (1-7), together with seven known sesquiterpenes, aplysin
      (8), aplysinol (9), gossonorol (10), 7,10-epoxy-ar-bisabol-11-ol (11), 10-epi
      7,10-epoxy-ar-bisabol-11-ol (12), johnstonol (13), and laurebiphenyl (14), have
      been isolated from the red alga Laurencia tristicha. The structures of new
      compounds were established as laur-11-en-2,10-diol (1), laur-11-en-10-ol (2),
      laur-11-en-1,10-diol (3), 4-bromo-1,10-epoxylaur-11-ene (4), cyclolauren-2-ol
      (5), laurentristich-4-ol (6), and ar-bisabol-9-en-7,11-diol (7) by means of
      spectroscopic methods including IR, HRMS, and 1D and 2D NMR techniques. Compound
      6 possessed a novel rearranged skeleton. All compounds were tested against
      several human cancer cell lines including lung adenocarcinoma (A549), stomach
      cancer (BGC-823), hepatoma (Bel 7402), colon cancer (HCT-8), and HELA cell lines.
      Laurebiphenyl (14) showed moderate cytotoxicity against all tested cell lines,
      with IC(50) values of 1.68, 1.22, 1.91, 1.77, and 1.61 microg/mL, respectively.
      Other compounds were inactive (IC(50) > 10 microg/mL).

PMID- 15974620
TI  - Grayanane diterpenoids from the flowers of Rhododendron molle with cytotoxic
      activity against a Spodoptera frugiperda cell line.
AB  - Two new grayanane diterpenoids, rhodomolins A (1) and B (2), together with two
      known diterpenoids, rhodomolleins I and rhodojaponin III, were isolated from the
      flowers of Rhododendron molle. The structures of 1 and 2 were elucidated on the
      basis of interpretation of spectroscopic data. All compounds were evaluated for
      cytotoxic activity against the Spodoptera frugiperda cell line Sf-9 and gave
      IC(50) values in the range 12-80 microg/mL.

PMID- 15974621
TI  - Constituents of the leaves of Macaranga tanarius.
AB  - From the leaves of Macaranga tanarius, three new constituents, tanarifuranonol
      (1), tanariflavanone C (2), and tanariflavanone D (3), together with seven known
      compounds, were isolated and identified. Substances obtained in this
      investigation were evaluated against a panel of bioassays.

PMID- 15974622
TI  - Polyprenylated benzophenone derivatives from Cuban propolis.
AB  - Three new polyprenylated benzophenone derivatives, propolones B-D (5-7), together
      with garcinielliptone I (8) and hyperibone B (9), were isolated from Cuban
      propolis. All the structures, including relative configurations, were elucidated
      by spectroscopic methods and computer-generated molecular modeling.

PMID- 15974623
TI  - Taxezopidines M and N, taxoids from the Japanese yew, Taxus cuspidata.
AB  - Two new taxoids, taxezopidines M (1) and N (2), have been isolated from seeds of
      the Japanese yew, Taxus cuspidata, and new structures were elucidated on the
      basis of spectroscopic data. The absolute configuration of a 3-N,N
      (dimethylamino)-3-phenylpropanoyl group in 1 and 2 was determined to be R in each
      case by chiral HPLC analysis. The effect of 1 and 2 on the CaCl(2)-induced
      depolymerization of microtubules was investigated.

PMID- 15974624
TI  - 1,3-Dimethyllumazine derivatives from Limnatis nilotica.
AB  - Two previously unknown lumazine derivatives, 1 and 2, have been isolated from the
      parasitic freshwater leech Limnatis nilotica. The structures of the compounds
      have been elucidated by NMR and unambiguously corroborated by chemical synthesis.

PMID- 15974625
TI  - Confirmation of the structure of (3S)-3-hydroxyquinine: synthesis and X-ray
      crystal structure of its 9-aceto analogue.
AB  - 3(S)-3-Hydroxyquinine (2) has been separated from its epimeric mixture at C-3 by
      conversion into the 9-aceto analogue followed by chromatography. The molecular
      structure of the acetate was determined through single-crystal X-ray analysis,
      and this confirms the structure of (3S)-3-hydroxyquinine (2), the major
      metabolite of quinine (1).

PMID- 15974626
TI  - A cytotoxic xanthone dimer from the entomopathogenic fungus Aschersonia sp. BCC
      8401.
AB  - Ascherxanthone A (1), a novel symmetrical tetrahydroxanthone dimer, was isolated
      from the entomopathogenic fungus Aschersonia sp. BCC 8401. The structure of 1 was
      elucidated by spectroscopic analysis, especially 2D-NMR. Compound 1 exhibited
      activity against Plasmodium falciparum K1 with an IC(50) value of 0.20 microg/mL,
      but it also showed cytotoxic activities against Vero cells and three tumor cell
      lines.

PMID- 15974627
TI  - Terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline
      inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells.
AB  - Klugine (1), isocephaeline (2), and emetine (4) inhibited hypoxia-inducible
      factor-1 (HIF-1) activation by hypoxia in T47D breast tumor cells (IC(50) values
      0.2, 1.1, and 0.11 muM, respectively). Compounds 1, 2, and 4 inhibited both
      hypoxia- and iron chelator-induced HIF-1 activation by blocking HIF-1alpha
      protein accumulation.

PMID- 15974628
TI  - Hectochlorin and morpholine derivatives from the Thai sea hare, Bursatella
      leachii.
AB  - Investigation of the EtOAc extract from the Thai sea hare, Bursatella leachii,
      resulted in the isolation of a potent stimulator of actin assembly, hectochlorin
      (1), and its new derivative, deacetylhectochlorin (2). Compound 2 exhibited more
      potent cytotoxicity than 1 against different human carcinoma cell lines. In
      addition, a new morpholine-2,5-dione analogue, syn-3-isopropyl-6-(4
      methoxybenzyl)-4-methylmorpholine-2,5-dione (3), was co-isolated.

PMID- 15974629
TI  - Alkaloids and aromatics of Cyathobasis fruticulosa (Bunge) Aellen.
AB  - A beta-carboline-, a tryptamine-, and two phenylethylamine-derived alkaloids and
      three known aromatic compounds were isolated from the aerial parts and roots of
      Cyathobasis fruticulosa (Bunge) Aellen, and their structures were elucidated by
      spectroscopic techniques. The one new alkaloid, N-methyl-N-formyl-4-hydroxy-beta
      phenylethylamine (1), showed marginal antifungal activity.

PMID- 15974630
TI  - Phytotoxins from Hofmeisteria schaffneri: isolation and synthesis of 2'-(2' '
      hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate1.
AB  - Activity-directed fractionation of a CH(2)Cl(2)-MeOH (1:1) extract of
      Hofmeisteria schaffneri led to the isolation of a new phytotoxin characterized as
      2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate and designated the
      trivial name of hofmeisterin (1). In addition, the known compounds beta-carotene,
      euparin, and 3',4',4a',9a'-tetrahydro-6,7'-dimethylspiro[benzofuran-3(2H),2'
      pyrano[2,3-b]benzofuran]-2,4a'-diol (2) were obtained. The identification of the
      isolates was accomplished by spectroscopic methods. The structure of 1 was
      unequivocally confirmed by synthesis. The methyl derivative 1a was also
      synthesized following the same strategy. Compounds 1 and 2 inhibited radicle
      growth of Amaranthus hypochondriacus (IC(50) = 3.2 x 10(-4) and 1.2 x 10(-5) M,
      respectively) and significantly inhibited activation of the calmodulin (CaM)
      dependent enzyme cAMP phosphodiesterase (PDE) with IC(50) values of 4.4 and 4.22
      microM, respectively.

PMID- 15974632
TI  - Exercise and the lymphatic system: implications for breast-cancer survivors.
AB  - This article summarises the current research on the lymphatic system related to
      exercise and critically evaluates the implications for exercise performance by
      breast-cancer survivors. The primary role of the lymphatic system during exercise
      is to assist in the regulation of tissue volume and pressure by carrying fluid
      and plasma proteins that have leaked into the interstitial space from tissues
      back to the cardiovascular system. During steady-state exercise in humans, lymph
      flow has been shown to increase to levels approximately 2- to 3-fold higher than
      at rest. Although the lymphatic system does not typically limit exercise
      performance in the normal population, the function of this system can be impaired
      in 27-49% of women who have survived breast cancer. Breast cancer-related
      lymphoedema (BCRL) is a chronic swelling that can occur in the ipsilateral hand
      or arm of women treated for breast cancer and results in a number of physical and
      psychological sequelae. Exercise was once believed to be a factor in the
      development of BCRL as it was thought that the damage to the axillary lymphatics
      from breast-cancer treatment resulted in a primary obstruction to lymph flow.
      However, the exact aetiology and pathophysiology of BCRL appears to be multi
      factorial and not as simple as a 'stop-cock' effect. Furthermore, recent studies
      have shown that participating in vigorous, upper-body exercise is not related to
      an increase in arm volume, which would indicate the development of BCRL. It is
      still not known, though, how long-term exercise affects lymphatic system function
      in breast-cancer survivors with and without BCRL.

PMID- 15974633
TI  - The role of apoptosis in age-related skeletal muscle atrophy.
AB  - Skeletal myocyte atrophy and death contribute to sarcopenia, a condition
      associated with normal aging. By 80 years of age, it is estimated that humans
      generally lose 30-40% of skeletal muscle fibres. The mechanism for this loss is
      unknown; however, it may involve apoptosis. Mitochondrial dysfunction and
      sarcoplasmic reticulum (SR) stress that occurs with age may be possible stimuli
      inducing apoptosis. Hence, mitochondria and SR may be important organelles within
      skeletal myocytes responsible for apoptosis signalling. The activation of
      apoptosis may be partly responsible for the initiation of muscle protein
      degradation, loss of muscle nuclei associated with local atrophy, and cell death
      of the myocyte. Exercise training and caloric restriction are two interventions
      known to enhance skeletal muscle function. The effects of these interventions on
      apoptosis are discussed.

PMID- 15974634
TI  - Exercise and chronic kidney disease: current recommendations.
AB  - Patients with chronic kidney disease (CKD) are inactive and have reduced physical
      functioning and performance. Aerobic exercise interventions have been shown to
      increase maximal oxygen consumption in selected patients. In addition,
      preliminary evidence, although mixed, suggests that aerobic exercise training can
      improve blood pressure control, lipid profiles and mental health in this
      population. A few larger studies are now available showing that aerobic training
      can also improve physical functioning and performance. The impact on survival or
      hospitalisation has not been determined. Resistance exercise training, although
      less studied, appears to increase muscle strength and size and may also improve
      functioning. There have been several reports of successful combined exercise
      interventions, but the designs have not allowed evaluation of the relative
      benefits of aerobic and resistance training on physical functioning. Despite the
      evidence that exercise is safe and beneficial in patients with CKD, dialysis
      patients remain inactive, and exercise assessment, counselling and training is
      not widely offered to patients with CKD. Studies of the barriers to patient
      participation in exercise and to provider assessment and recommendations are
      needed so that more widely generalisable interventions can be developed. However,
      in the interim, patients should be encouraged to participate in moderate physical
      activity to meet the US Surgeon General's recommendations. Patients who are weak
      can benefit from strength-training interventions. Resistance and aerobic exercise
      programmes should be initiated at relatively low intensity in patients with CKD
      and progressed as slowly as tolerated in order to avoid injury and
      discontinuation of exercise. For patients on haemodialysis, incorporation of
      exercise into the dialysis session may increase patient participation and
      tolerance of exercise.

PMID- 15974635
TI  - Physiology of soccer: an update.
AB  - Soccer is the most popular sport in the world and is performed by men and women,
      children and adults with different levels of expertise. Soccer performance
      depends upon a myriad of factors such as technical/biomechanical, tactical,
      mental and physiological areas. One of the reasons that soccer is so popular
      worldwide is that players may not need to have an extraordinary capacity within
      any of these performance areas, but possess a reasonable level within all areas.
      However, there are trends towards more systematic training and selection
      influencing the anthropometric profiles of players who compete at the highest
      level. As with other activities, soccer is not a science, but science may help
      improve performance. Efforts to improve soccer performance often focus on
      technique and tactics at the expense of physical fitness. During a 90-minute
      game, elite-level players run about 10 km at an average intensity close to the
      anaerobic threshold (80-90% of maximal heart rate). Within this endurance
      context, numerous explosive bursts of activity are required, including jumping,
      kicking, tackling, turning, sprinting, changing pace, and sustaining forceful
      contractions to maintain balance and control of the ball against defensive
      pressure. The best teams continue to increase their physical capacities, whilst
      the less well ranked have similar values as reported 30 years ago. Whether this
      is a result of fewer assessments and training resources, selling the best
      players, and/or knowledge of how to perform effective exercise training regimens
      in less well ranked teams, is not known. As there do exist teams from lower
      divisions with as high aerobic capacity as professional teams, the latter factor
      probably plays an important role. This article provides an update on the
      physiology of soccer players and referees, and relevant physiological tests. It
      also gives examples of effective strength- and endurance-training programmes to
      improve on-field performance. The cited literature has been accumulated by
      computer searching of relevant databases and a review of the authors' extensive
      files. From a total of 9893 papers covering topics discussed in this article, 843
      were selected for closer scrutiny, excluding studies where information was
      redundant, insufficient or the experimental design was inadequate. In this
      article, 181 were selected and discussed. The information may have important
      implications for the safety and success of soccer players and hopefully it should
      be understood and acted upon by coaches and individual soccer players.

PMID- 15974636
TI  - Rowing injuries.
AB  - Participation in the sport of rowing has been steadily increasing in recent
      decades, yet few studies address the specific injuries incurred. This article
      reviews the most common injuries described in the literature, including
      musculoskeletal problems in the lower back, ribs, shoulder, wrist and knee. A
      review of basic rowing physiology and equipment is included, along with a
      description of the mechanics of the rowing stroke. This information is necessary
      in order to make an accurate diagnosis and treatment protocol for these injuries,
      which are mainly chronic in nature. The most frequently injured region is the low
      back, mainly due to excessive hyperflexion and twisting, and can include specific
      injuries such as spondylolysis, sacroiliac joint dysfunction and disc herniation.
      Rib stress fractures account for the most time lost from on-water training and
      competition. Although theories abound for the mechanism of injury, the exact
      aetiology of rib stress fractures remains unknown. Other injuries discussed
      within, which are specific to ribs, include costochondritis, costovertebral joint
      subluxation and intercostal muscle strains. Shoulder pain is quite common in
      rowers and can be the result of overuse, poor technique, or tension in the upper
      body. Injuries concerning the forearm and wrist are also common, and can include
      exertional compartment syndrome, lateral epicondylitis, deQuervain's and
      intersection syndrome, and tenosynovitis of the wrist extensors. In the lower
      body, the major injuries reported include generalised patellofemoral pain due to
      abnormal patellar tracking, and iliotibial band friction syndrome. Lastly,
      dermatological issues, such as blisters and abrasions, and miscellaneous issues,
      such as environmental concerns and the female athlete triad, are also included in
      this article.Pathophysiology, mechanism of injury, assessment and management
      strategies are outlined in the text for each injury, with special attention given
      to ways to correct biomechanical or equipment problems specific to rowing. By
      gaining an understanding of basic rowing biomechanics and training habits, the
      physician and/or healthcare provider will be better equipped to treat and prevent
      injuries in the rowing population.

PMID- 15974637
TI  - Late-onset ankylosing spondylitis and related spondylarthropathies: clinical and
      radiological characteristics and pharmacological treatment options.
AB  - Ankylosing spondylitis is the prototype of related diseases commonly called
      spondylarthropathies which include reactive arthritis, psoriatic arthritis,
      arthritis associated with inflammatory bowel diseases (enteropathic arthritis)
      and undifferentiated spondylarthropathies. Ankylosing spondylitis and
      spondylarthropathies are generally observed in young patients but can be observed
      later in life or in persons >50 years of age. All the spondylarthropathy
      subgroups are represented in the elderly with some features particular to this
      age group. Indeed, radiological aspects of ankylosing spondylitis may be
      difficult to interpret because of the radiological changes induced by aging. Late
      onset peripheral spondylarthropathies are characterised by severe disease, marked
      elevation of laboratory parameters of inflammation, oligoarthritis involving the
      lower limbs and oedema of the extremities. Psoriatic arthritis is more severe in
      the elderly and is associated with worse outcomes than in young patients. The
      clinical presentation of undifferentiated spondylarthropathy is as varied in the
      elderly as in young and middle-aged adults. Reactive arthritis and enteropathic
      arthritis are observed in the elderly more rarely. The effects of aging on drug
      metabolism and pharmacokinetics, together with the existence of co-morbidities
      and polypharmacy, are responsible for difficulties in the therapeutic management
      of late-onset ankylosing spondylitis or spondylarthropathies. Indeed, NSAIDs
      should be used with caution in older patients because of the high risk of serious
      gastrointestinal complications. Sulfasalazine and methotrexate have been used as
      disease-controlling drugs but did not prove very effective. Pamidronate and
      tumour necrosis factor (TNF)-alpha antagonists offer a therapeutic alternative
      but have not been specifically tested in the elderly. Pamidronate has been tested
      in young-onset ankylosing spondylitis and spondylarthropathies with conflicting
      results but can be used in older patients without risk of major adverse effects.
      TNFalpha antagonists have been adequately evaluated in ankylosing spondylitis and
      spondylarthropathies and are associated with dramatic improvement in clinical and
      biological parameters of disease activity. However, the safety profile of these
      agents in the elderly is not currently known and careful surveillance, in
      particular for the risk of infection such as tuberculosis, and/or exacerbation of
      chronic heart failure, is thus required when using these drugs in this age group.

PMID- 15974638
TI  - Adenosine A2A receptor antagonists for Parkinson's disease: rationale,
      therapeutic potential and clinical experience.
AB  - Long-term disability in Parkinson's disease (PD) is related to progression of the
      underlying disease and the emergence of complications of chronic levodopa
      therapy. There is a need for new medications that can slow the underlying
      progression of degeneration, improve PD symptoms in early disease without
      inducing dyskinesia, and improve motor fluctuations and 'off' time in advanced
      disease without worsening dyskinesia. Much interest has focused on the
      development of nondopaminergic therapies, with antagonists of the adenosine A2A
      receptor emerging as leading candidates. A2A receptors are selectively expressed
      in the basal ganglia and specific A2A antagonists reverse motor deficits without
      causing dyskinesia in animal models of PD. The antiparkinsonian potential of A2A
      receptor blockade has been expanded further by convergent epidemiological and
      laboratory findings suggesting a possible neuroprotective effect of A2A receptor
      antagonists in PD. Istradefylline (KW-6002) is the first of several adenosine A2A
      receptor antagonists in development for PD to advance to phase III clinical
      trials. Initial studies indicate that in patients with motor fluctuations on
      levodopa, addition of istradefylline reduces 'off' time. Additional studies are
      necessary to evaluate the benefit of istradefylline as monotherapy in early
      disease, its effect on the development of dyskinesia, and its effect on disease
      progression.

PMID- 15974641
TI  - Reducing the risk of stroke in elderly patients with hypertension: a critical
      review of the efficacy of antihypertensive drugs.
AB  - The risk of ischaemic or haemorrhagic stroke is increased in patients with
      hypertension, with a linear relationship between elevation of blood pressure and
      stroke risk being seen even in normotensive individuals. In elderly subjects it
      has been shown that systolic blood pressure (SBP) elevation in particular is the
      most important risk predictor for stroke. This is also the rationale for treating
      elevated SBP in the elderly. Several clinical trials have repeatedly shown the
      benefits of blood pressure control for prevention of stroke and also for
      dementia, both of the multi-infarct and Alzheimer subtype. Remaining research
      questions involve the proper and evidence-based choice of drug treatment in the
      elderly hypertensive patient. In spite of the introduction of many newer
      antihypertensive drugs, use of thiazide diuretics is still one of the best
      treatment choices, as this class of drugs is well proven and cost effective.
      Another question concerns when and how to treat patients >80 years of age. An
      ongoing randomised clinical trial, the Hypertension in the Very Elderly trial, is
      currently trying to evaluate risks and benefits of antihypertensive treatment in
      this age category.

PMID- 15974640
TI  - Influenza vaccination in the elderly: impact on hospitalisation and mortality.
AB  - Influenza causes substantial morbidity across the age spectrum. However, the
      elderly are especially vulnerable to the serious complications of influenza that
      might result in hospitalisation or death, and high rates of influenza-associated
      excess hospitalisation or death that exceed by several-fold the rates seen among
      most other age groups have consistently been observed in many countries and
      across many seasons. Thus, the elderly are included among the high priority
      groups for routine influenza vaccination by many national health authorities.
      Inactivated influenza virus vaccines are widely available across the globe and
      are safe and effective. Vaccination of elderly persons has been associated with
      significant reductions in hospitalisations for pneumonia and influenza as well as
      hospitalisations for other cardiopulmonary disorders and even cerebrovascular
      disease. Vaccination has also been associated with reductions in influenza
      associated and all-cause mortality during influenza seasons. The benefits of
      vaccination extend not only to community-dwelling elderly but also to elderly who
      reside in nursing homes. Likewise, vaccination provides benefits to the very old
      and to elderly persons with underlying co-morbidities as well as to the healthy
      elderly. Despite the substantially increased risk for serious complications and
      impressive benefits from vaccination among the elderly, influenza vaccine
      utilisation remains below target rates for this group in nearly all countries.
      The need for improved prevention and control of influenza is recognised as a
      priority for the global community--both to reduce the morbidity and mortality
      associated with epidemic influenza and to prepare for the next pandemic.
      Enhancing vaccine delivery to elderly persons would represent important progress
      toward that goal.

PMID- 15974643
TI  - Unimolecular dissociation and thermochemistry of CH3OOH.
AB  - The unimolecular dissociation of CH3OOH is investigated by exciting the molecule
      in the region of its 5nu(OH) band and probing the resulting OH fragments using
      laser-induced fluorescence. The measured OH fragment rotational and translational
      energies are used to determine the CH3O-OH bond dissociation energy, which we
      estimate to be approximately 42.6+/-1 kcal/mol. Combining this value with the
      known heats of formation of the fragments also gives an estimate for the heat of
      formation of CH3OOH which at 0 K we determine to be deltaH(f)0=-27+/-1 kcal/mol.
      This experimental value is in good agreement with the results of ab initio
      calculations carried out at the CCSD(T)/complete basis set limit which finds the
      heat of formation of CH3OOH at 0 K to be deltaH(f)0=-27.3 kcal/mol.

PMID- 15974639
TI  - Poststroke dementia in the elderly.
AB  - Risk of dementia increases after stroke, and poststroke dementia (PSD) is an
      important cause of disability in the elderly. The prevalence rates of PSD vary
      from 12.2% to 31.8% within 3 months to 1 year after stroke, depending on patient
      populations and the diagnostic criteria used in the numerous studies. Incidence
      rates of PSD increase with time after the stroke. Although vascular lesions and
      white matter changes can explain the cognitive disorders seen in stroke patients,
      an underlying neurodegenerative disorder may contribute to the development of
      PSD. Cognitive decline may pre-date the stroke and follow a progressive course
      after the stroke. The vascular and degenerative processes involved share common
      environmental and genetic risk factors. This review explains the mechanisms of
      dementia in stroke patients and identifies predictive factors for PSD. The
      following points are successively considered: (i) demographic characteristics of
      the patients, including age and level of education; (ii) prestroke cognitive
      decline; (iii) vascular risk factors, including diabetes mellitus and prior
      strokes; (iv) stroke characteristics, including severity and location of the
      vascular lesion; (v) co-morbid disorders; and (vi) abnormalities on brain
      imaging, including location, size and number of vascular lesions, white matter
      changes and cerebral atrophy. Older age, prestroke cognitive decline, stroke
      recurrence, hypoxic-ischaemic disorders, left-side infarcts, strategic infarcts
      and white matter lesions appear to be the main predictive factors of PSD.
      Prevention of stroke should reduce the morbidity and mortality associated with
      PSD. In addition, management of PSD with secondary prevention treatments could
      reduce occurrence of further strokes. Cholinesterase inhibitors may be beneficial
      not only in Alzheimer's disease associated with cerebrovascular lesions, but also
      for the treatment of cholinergic dysfunction arising from pure vascular dementia.
      Better knowledge of the risk factors for PSD, including environmental and genetic
      factors, should increase the effectiveness of preventive strategies in patients
      with this condition.

PMID- 15974644
TI  - A full nine-dimensional potential-energy surface for hydrogen molecule-water
      collisions.
AB  - The hydrogen and water molecules are ubiquitous in the Universe. Their mutual
      collisions drive water masers and other line emission in various astronomical
      environments, notably molecular clouds and star-forming regions. We report here a
      full nine-dimensional interaction potential for H2O-H2 calibrated using high
      accuracy, explicitly correlated wave functions. All degrees of freedom are
      included using a systematic procedure transferable to other small molecules of
      astrophysical or atmospherical relevance. As a first application, we present rate
      constants for the vibrational relaxation of the upsilon2 bending mode of H2O
      obtained from quasiclassical trajectory calculations in the temperature range of
      500-4000 K. Our high-temperature (T > or = 1500 K) results are found compatible
      with the single experimental value at 295 K. Our rates are also significantly
      larger than those currently used in the astrophysical literature and will lead to
      a thorough reinterpretation of vibrationally excited water emission spectra from
      space.

PMID- 15974642
TI  - Clinical assessment of effects of botanical supplementation on cytochrome P450
      phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo
      biloba.
AB  - OBJECTIVES: Elderly patients are more likely to ingest prescription medications
      concurrently with botanical supplements, and may therefore be vulnerable to herb
      drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP)
      activity may underlie many herb-drug interactions. Some evidence suggests that
      CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP
      activity may take on greater clinical relevance in this population. In this
      study, single timepoint, phenotypic metabolic ratios were used to determine
      whether long-term supplementation of St John's wort, garlic oil, Panax ginseng,
      and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly
      subjects. METHODS: Twelve healthy volunteers between the ages of 60 and 76 years
      (mean age 67 years) were randomly assigned to receive each botanical supplement
      for 28 days followed by a 30-day washout period. Probe drug cocktails of
      midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and
      at the end of supplementation. Pre- and post-supplementation phenotypic ratios
      were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1
      hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum
      ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and
      debrisoquine urinary recovery ratios (8-hour), respectively. The content of
      purported 'active' phytochemicals was determined for each supplement. RESULTS:
      Comparisons of pre- and post-St John's wort phenotypic ratios revealed
      significant induction of CYP3A4 (approximately 140%) and CYP2E1 activity
      (approximately 28%). Garlic oil inhibited CYP2E1 activity by approximately 22%.
      P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude
      of the effect (approximately 7%) did not appear to be clinically relevant. None
      of the supplements tested in this study appeared to affect CYP1A2 activity.
      CONCLUSIONS: Elderly subjects, like their younger counterparts, are susceptible
      to herb-mediated changes in CYP activity, especially those involving St John's
      wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP
      activity may adversely affect drug efficacy and/or toxicity. When compared with
      earlier studies that employed young subjects, the data suggest that some age
      related changes in CYP responsivity to botanical supplementation may exist.
      Concomitant ingestion of botanical supplements with prescription medications,
      therefore, should be strongly discouraged in the elderly.

PMID- 15974645
TI  - A practical treatment for the three-body interactions in the transcorrelated
      variational Monte Carlo method: application to atoms from lithium to neon.
AB  - We suggest a practical solution to dealing with the three-body interactions in
      the transcorrelated variational Monte Carlo method (TC-VMC). In the TC-VMC
      method, which was suggested in our previous paper [N. Umezawa and S. Tsuneyuki,
      J. Chem. Phys. 119, 10015 (2003)], the Jastrow-Slater-type wave function is
      efficiently optimized through a self-consistent procedure by minimizing the
      variance of the local energy. The three-body terms in the transcorrelated self
      consistent-field equation, which have been simply ignored in our previous works,
      are efficiently calculated by the Monte Carlo numerical integration. We found
      that our treatment for the three-body interactions is successful for atoms from
      Li to Ne.

PMID- 15974646
TI  - Critical comparison of various connected quadruple excitation approximations in
      the coupled-cluster treatment of bond breaking.
AB  - To assess the limits of single-reference coupled-cluster (CC) methods for
      potential-energy surfaces, several methods have been considered for the inclusion
      of connected quadruple excitations. Most are based upon the factorized inclusion
      of the connected quadruple contribution (Qf) [J. Chem. Phys. 108, 9221 (1998)].
      We compare the methods for the treatment of potential-energy curves for small
      molecules. These include CCSD(TQf), where the initial contributions of triple (T)
      and factorized quadruple excitations are added to coupled-cluster singles (S) and
      doubles (D), its generalization to CCSD(TQf), where instead of measuring their
      first contribution from orders in H, it is measured from orders in H=e(
      (T1+T2))He(T1+T2); renormalized approximations of both, and CCSD2 defined in [J.
      Chem. Phys. 115, 2014 (2001)]. We also consider CCSDT, CCSDT(Qf), CCSDTQ, and
      CCSDTQP for comparison, where T, Q, and P indicate full triple, quadruple, and
      pentuple excitations, respectively. Illustrations for F2, the double bond
      breaking in water, and N2 are shown, including effects of quadruples on
      equilibrium geometries and vibrational frequencies. Despite the fact that no
      perturbative approximation, as opposed to an iterative approximation, should be
      able to separate a molecule correctly for a restricted-Hartree-Fock reference
      function, some of these higher-order approximations have a role to play in
      developing new, more robust procedures.

PMID- 15974647
TI  - Quantifying the effects of the self-interaction error in DFT: when do the
      delocalized states appear?
AB  - The self-interaction error in density-functional theory leads to artificial
      stabilization of delocalized states, most evident in systems with an odd number
      of electrons. Clear examples are dissociations of carbocation radicals that often
      give delocalized states at long distances and large errors in computed binding
      energies. On the other hand, many mixed-valence transition-metal dimers known to
      exhibit valence trapping are correctly predicted to be localized. To understand
      the effects of the self-interaction error on these different systems, energy
      differences between delocalized and localized states are calculated with B3LYP.
      In the dissociation of radicals into symmetric fragments at infinite distance,
      this energy difference equals the error of the density-functional treatment. The
      energy difference decreases with increasing size of the system, from 55 kcal/mol
      in H2(+) to 15 kcal/mol for C12H26(+). Solvent corrections stabilize the
      localized state and result in smaller errors. Most reactions are asymmetric and
      this decreases the effect of the self-interaction error. In many systems,
      delocalization will not occur if the cost to move the electron from one fragment
      to the other is 70-80 kcal/mol (3.0-3.5 eV). This estimate refers to a situation
      where the distance between the fragments is infinite. The limit decreases with
      decreasing fragment distance. B3LYP calculations on the ferromagnetic state of a
      Mn(III,IV) dimer predict that the correct localized state is 22 kcal/mol more
      stable than the incorrect delocalized state. At short metal-metal distances the
      effect of the self-interaction error is predicted to be small. However, as the
      distance between the two manganese centers is increased to 7 A, the dimer starts
      to delocalize and the energy artificially decreases. In the dissociation limit,
      the error is 10 kcal/mol. This is interpreted as an artifact originating from the
      self-interaction error. Delocalization is not encountered in many systems due to
      relatively short metal-metal distances and asymmetric ligand environments.
      However, some charge-transfer complexes cannot be properly calculated and
      delocalized states may become a problem in large models of enzyme systems with
      multiple transition-metal complexes.

PMID- 15974648
TI  - Time-dependent density-functional theory calculations of triplet-triplet
      absorption.
AB  - We present density-functional theory calculations of triplet-triplet absorption
      by three different approaches based on time-dependent density-functional theory
      (DFT): unrestricted DFT linear response, open-shell restricted DFT linear
      response applied to the triplet state, and quadratic response with triplet
      excitations applied to the ground state. Comparison is also made with
      corresponding results obtained by Hartree-Fock and multiconfiguration self
      consistent-field response theory. Two main conclusions concerning triplet-triplet
      transitions are drawn in this study: First, the very good agreement between
      unrestricted and restricted DFT results indicates that spin contamination of the
      triplet state is not a serious problem when computing triplet-triplet spectra of
      common organic molecules. Second, DFT response calculations of triplet-triplet
      transitions can be affected by triplet instability problems, especially for the
      combination of DFT quadratic response with functionals containing fractional
      exact Hartree-Fock exchange.

PMID- 15974649
TI  - Eckart axis conditions and the minimization of the root-mean-square deviation:
      two closely related problems.
AB  - We highlight the fact that the rotation matrix minimizing the root-mean-square
      deviation between two molecular conformations [W. Kabsch, Acta Cryst. A32, 922
      (1976)] also satisfies the Eckart axis conditions [C. Eckart, Phys. Rev. 47, 552
      (1935)].

PMID- 15974650
TI  - Analytic gradients for the spin-conserving and spin-flipping equation-of-motion
      coupled-cluster models with single and double substitutions.
AB  - Analytic gradient expressions for the spin-conserving and spin-flipping equation
      of-motion coupled-cluster models with single and double substitutions are derived
      using a Lagrangian approach for the restricted and unrestricted Hartree-Fock
      references, both for the case of all orbitals being active in correlated
      calculations and for the frozen core and/or virtual orbitals. Details of the
      implementation within the Q-CHEM electronic structure package are discussed. The
      capabilities of the new code are demonstrated by application to cyclobutadiene.

PMID- 15974651
TI  - Compact multipolar representation of the electrostatic potential for flexible
      molecules.
AB  - A new method for generating a compact multipolar representation of the
      electrostatic potential (EP) for flexible molecules is presented. The method is
      based on a constrained minimization of the difference between the quantum
      mechanical and the classical EP. The fitting procedure used adopts the least
      absolute shrinkage and selection operator technique [R. Tibshirani, J. Roy. Stat.
      Soc. B 58, 267 (1996)] which can be seen as penalized ordinary least squares. The
      penalty function optimized for the particular molecule of interest effectively
      removes redundant multipoles. It is shown that the use of multiple conformations
      is crucial for the predictive ability of the EP model for flexible molecules. The
      multipole local coordinate systems are chosen in a way that best reflects the key
      conformational changes. It was demonstrated that such an approach improves the
      predictive ability of EP models. It also allows to exploit equivalence of atoms
      in the calculation of multipoles components. In the case of polar flexible
      molecules, the augmentation of the EP model based on charges by higher multipoles
      decreases the relative root mean square error by a factor of 1.5-5. The
      corresponding effect of enlargement of the set of multipoles was significantly
      reduced.

PMID- 15974652
TI  - Electronic energy levels with the help of trajectory-guided random grid of
      coupled wave packets. I. Six-dimensional simulation of H2.
AB  - As a preliminary to future work on the behavior of atoms and molecules in strong
      time-dependent fields, we apply the coupled coherent-states (CCS) technique of
      multidimensional phase-space quantum dynamics to obtain Born-Oppenheimer energy
      levels of electrons in molecules. Unlike traditional approaches based on atomic
      and molecular-orbital basis sets and time-independent Schrodinger equation the
      CCS method exploits the solution of the time-dependent Schrodinger equation in
      the basis of Monte Carlo-selected trajectory-guided coherent states, which treat
      classical electron correlations exactly. In addition the CCS trajectories move
      over averaged potentials, which remove the Coulombic singularities.

PMID- 15974653
TI  - A version of diffusion Monte Carlo method based on random grids of coherent
      states. II. Six-dimensional simulation of electronic states of H2.
AB  - We report a new version of the diffusion Monte Carlo (DMC) method, based on
      coherent-state quantum mechanics. Randomly selected grids of coherent states in
      phase space are used to obtain numerical imaginary time solutions of the
      Schrodinger equation, with an iterative refinement technique to improve the
      quality of the Monte Carlo grid. Accurate results were obtained, for the
      appropriately symmetrized two lowest states of the hydrogen molecule, by Monte
      Carlo sampling and six-dimensional propagation in the full phase space.

PMID- 15974654
TI  - Molecular applications of the intermediate Hamiltonian Fock-space coupled-cluster
      method for calculation of excitation energies.
AB  - The intermediate Hamiltonian Fock-space coupled-cluster (FS-CC) method with
      singles and doubles is applied to calculate vertical excitation energies (EEs)
      for some molecular systems. The calculations are performed for several small
      molecules, such as H2O, N2, and CO, and for larger systems, such as C2H4, C4H6,
      and C6H6. Due to the intermediate Hamiltonian formulation, which provides a
      robust computational scheme for solving the FS-CC equations, and the efficient
      factorization strategy, relatively large basis sets and model spaces are employed
      permitting a comparison of the calculated vertical EEs with the experimental
      data.

PMID- 15974655
TI  - The microcanonical thermodynamics of finite systems: the microscopic origin of
      condensation and phase separations, and the conditions for heat flow from lower
      to higher temperatures.
AB  - Microcanonical thermodynamics [D. H. E. Gross, Microcanonical Thermodynamics,
      Phase Transitions in "Small" Systems (World Scientific, Singapore, 2001)] allows
      the application of statistical mechanics both to finite and even small systems
      and also to the largest, self-gravitating ones. However, one must reconsider the
      fundamental principles of statistical mechanics especially its key quantity,
      entropy. Whereas in conventional thermostatistics, the homogeneity and
      extensivity of the system and the concavity of its entropy are central
      conditions, these fail for the systems considered here. For example, at phase
      separation, the entropy S(E) is necessarily convex to make e(S(E)-E/T) bimodal in
      E. Particularly, as inhomogeneities and surface effects cannot be scaled away,
      one must be careful with the standard arguments of splitting a system into two
      subsystems, or bringing two systems into thermal contact with energy or particle
      exchange. Not only the volume part of the entropy must be considered; the
      addition of any other external constraint [A. Wehrl, Rev. Mod. Phys. 50, 221
      (1978)], such as a dividing surface, or the enforcement of gradients of the
      energy or particle profile, reduce the entropy. As will be shown here, when
      removing such constraints in regions of a negative heat capacity, the system may
      even relax under a flow of heat (energy) against a temperature slope. Thus the
      Clausius formulation of the second law: "Heat always flows from hot to cold," can
      be violated. Temperature is not a necessary or fundamental control parameter of
      thermostatistics. However, the second law is still satisfied and the total
      Boltzmann entropy increases. In the final sections of this paper, the general
      microscopic mechanism leading to condensation and to the convexity of the
      microcanonical entropy at phase separation is sketched. Also the microscopic
      conditions for the existence (or nonexistence) of a critical end point of the
      phase separation are discussed. This is explained for the liquid-gas and the
      solid-liquid transition.

PMID- 15974656
TI  - Extended quantization condition for constructive and destructive interferences
      and trajectories dominating molecular vibrational eigenstates.
AB  - The role of destructive quantum interference in semiclassical quantization of
      molecular vibrational states is studied. This aspect is crucial for correct
      quantization, since failure in the appropriate treatment of destructive
      interference quite often results in many spurious peaks and broad background to
      hide the true peaks. We first study the time-Fourier transform of the
      autocorrelation function without performing summation over the trajectories. The
      resultant quantity, the prespectrum which is a function of individual classical
      trajectories, provides a clear view about how destructive interference among the
      trajectories should function. It turns out that the prespectrum is oscillatory
      but never a random noise. On the contrary, it bears a systematic and regular
      structure, which is sometimes characterized in terms of very sharp and high peaks
      in the energy space of the sampled classical trajectories. We have found an
      extended quantization condition that is responsible for generating these peaks in
      the prespectrum, which we call the prior quantization condition. Integration of
      the prespectrum over the trajectory space is supposed to give "zero" (practically
      a small value of the order of the Planck constant) at a noneigenvalue energy,
      which is actually a materialization of the destructive interference. Besides,
      certain finite peaks in the prespectrum survive after the integration to form the
      true spikes (eigenvalues) in the final spectrum, if they satisfy an additional
      resonance condition. For these resonance components, the prior quantization
      condition is reduced to the Einstein-Brillouin-Keller quantization condition.
      Based on these analyses, we propose a rather conventional filtering technique to
      efficiently handle tedious computation for destructive interference, and
      numerically verify that it works well even for multidimensional chaotic systems.
      This filtering technique is further utilized to extract a few trajectories that
      dominate an eigenstate of molecular vibration.

PMID- 15974657
TI  - Extrapolated intermediate Hamiltonian coupled-cluster approach: theory and pilot
      application to electron affinities of alkali atoms.
AB  - The intermediate Hamiltonian (IH) coupled-cluster method makes possible the use
      of very large model spaces in coupled-cluster calculations without running into
      intruder states. This is achieved at the cost of approximating some of the IH
      matrix elements, which are not taken at their rigorous effective Hamiltonian (EH)
      value. The extrapolated intermediate Hamiltonian (XIH) approach proposed here
      uses a parametrized IH and extrapolates it to the full EH, with model spaces
      larger by several orders of magnitude than those possible in EH coupled-cluster
      methods. The flexibility and resistance to intruders of the IH approach are thus
      combined with the accuracy of full EH. Various extrapolation schemes are
      described. A pilot application to the electron affinities (EAs) of alkali atoms
      is presented, where converged EH results are obtained by XIH for model spaces of
      approximately 20,000 determinants; direct EH calculations converge only for a one
      dimensional model space. Including quantum electrodynamic effects, the average
      XIH error for the EAs is 0.6 meV and the largest error is 1.6 meV. A new
      reference estimate for the EA of Fr is proposed at 486+/-2 meV.

PMID- 15974658
TI  - Time reversible and symplectic integrators for molecular dynamics simulations of
      rigid molecules.
AB  - Molecular dynamics integrators are presented for translational and rotational
      motion of rigid molecules in microcanonical, canonical, and isothermal-isobaric
      ensembles. The integrators are all time reversible and are also, in some
      approaches, symplectic for the microcanonical ensembles. They are developed
      utilizing the quaternion representation on the basis of the Trotter factorization
      scheme using a Hamiltonian formalism. The structure is similar to that of the
      velocity Verlet algorithm. Comparison is made with standard integrators in terms
      of stability and it is found that a larger time step is stable with the new
      integrators. The canonical and isothermal-isobaric molecular dynamics simulations
      are defined by using a chain thermostat approach according to generalized Nose
      Hoover and Andersen methods.

PMID- 15974659
TI  - Finite lifetime effects on the polarizability within time-dependent density
      functional theory.
AB  - We present an implementation for considering finite lifetime of the electronic
      excited states into linear-response theory within time-dependent density
      functional theory. The lifetime of the excited states is introduced by a common
      phenomenological damping factor. The real and imaginary frequency-dependent
      polarizabilities can thus be calculated over a broad range of frequencies. This
      allows for the study of linear-response properties both in the resonance and
      nonresonance cases. The method is complementary to the standard approach of
      calculating the excitation energies from the poles of the polarizability. The
      real and imaginary polarizabilities can then be calculated in any specific energy
      range of interest, in contrast to the excitation energies which are usually
      solved only for the lowest electronic states. We have verified the method by
      investigating the photoabsorption properties of small alkali clusters. For these
      systems, we have calculated the real and imaginary polarizabilities in the energy
      range of 1-4 eV and compared these with excitation energy calculations. The
      results showed good agreement with both previous theoretical and experimental
      results.

PMID- 15974660
TI  - Nuclear-magnetic-resonance shielding constants calculated by pseudospectral
      methods.
AB  - We have developed an algorithm based upon pseudospectral (PS) ab initio
      electronic structure methods for evaluating nuclear magnetic shielding constants
      using gauge-including atomic orbitals (GIAOs) in the spin-restricted and spin
      unrestricted formalisms of Hartree-Fock (HF) theory and density-functional theory
      (DFT). The nuclear magnetic shielding constants for both 1H and 13C calculated
      using PS methodology for 21 small molecules have absolute mean errors of less
      than 0.3 ppm in comparison with analytic integral results. CPU timing comparisons
      between PS methods and conventional methods carried out for seven large molecules
      ranging from 510 to 1285 basis functions demonstrate that the PS methods are an
      order of magnitude more efficient than the conventional methods. PS-HF was
      between 9 and 26 times faster than conventional integral technology, and PS-DFT
      (Becke three-parameter Lee-Yang-Parr) was between 6 and 21 times faster.

PMID- 15974661
TI  - Robust and accurate method for free-energy calculation of charged molecular
      systems.
AB  - A new approach is presented to eliminate the problem of creation and/or
      annihilation of atoms in free-energy calculations of charged molecular systems.
      The method employs a damping potential in the Ewald summation scheme, which is an
      exact solution of the electrostatics for three-dimensional periodic systems. The
      proposed method enables entire molecules to be mutated from a noninteracting
      (ideal) state in an efficient and robust way, thus providing a means by which
      accurate absolute free energies of structurally complex molecules can be
      determined. This methodology will enable chemical and phase equilibria to be
      determined for large molecular species with significant charge distributions,
      e.g., biomolecules and drugs.

PMID- 15974662
TI  - Supersonically cooled hydronium ions in a slit-jet discharge: high-resolution
      infrared spectroscopy and tunneling dynamics of HD2O+.
AB  - Jet-cooled high-resolution infrared spectra of partially deuterated hydronium ion
      (HD2O+) in the O-H stretch region (nu3 band) are obtained for the first time,
      exploiting the high ion densities, long absorption path lengths, and
      concentration modulation capabilities of the slit-jet discharge spectrometer.
      Least-squares analysis with a Watson asymmetric top Hamiltonian yields
      rovibrational constants and provides high level tests of ab initio molecular
      structure predictions. Transitions out of both the lower (nu3(+)<--0(+)) and the
      upper (nu3(-)<--0(-)) tunneling levels, as well as transitions across the
      tunneling gap (nu3(-)<--0(+)) are observed. The nu3(-)<--0(+) transitions in
      HD2O+ acquire oscillator strength by loss of D(3h) symmetry, and permit both
      ground-state-[27.0318(72) cm(-1)] and excited-state-[17.7612(54) cm(-1)]
      tunneling splittings to be determined to spectroscopic precision from a single
      rovibrational band. The splittings and band origins calculated with recent high
      level ab initio six-dimensional potential surface predictions for H3O+ and
      isotopomers [X. C. Huang, S. Carter, and J. M. Bowman, J. Chem. Phys. 118, 5431
      (2003); T. Rajamaki, A. Miani, and L. Halonen, J. Chem. Phys. 118, 10929 (2003)]
      are in very good agreement with the current experimental results.

PMID- 15974663
TI  - Investigation of valence orbitals of propene by electron momentum spectroscopy.
AB  - The binding energy spectra and momentum distributions of all valence orbitals of
      propene were studied by electron momentum spectroscopy (EMS) as well as Hartree
      Fock and density functional theoretical calculations. The experiment was carried
      out at impact energies of 1200 eV and 600 eV on the state-of-the-art EMS
      spectrometer developed at Tsinghua University recently. The experimental momentum
      profiles of the valence orbitals were obtained and compared with the various
      theoretical calculations. Moreover, the experiment with a new analysis method
      presents a strong support for the correct ordering of the orbital 8a' and 1a'',
      i.e., 9a' < 8a' < 1a'' < 7a'.

PMID- 15974664
TI  - Electron-impact excitation of D1delta <-- X1sigma+ in carbon monoxide.
AB  - The dipole-forbidden transition of D1delta <-- X1sigma+ of CO has been observed
      by a fast electron-energy-loss spectrometer at a large scattering angle of 7
      degrees and with an energy resolution of 60 meV. The energy levels and the
      relative intensity distribution of D1delta, v'=9-25 have been determined, most of
      the results are reported for the first time.

PMID- 15974665
TI  - Mechanistic and kinetic study of the CH3CO + O2 reaction.
AB  - Potential-energy surface of the CH3CO + O2 reaction has been calculated by ab
      initio quantum chemistry methods. The geometries were optimized using the second
      order Moller-Plesset theory (MP2) with the 6-311G(d,p) basis set and the coupled
      cluster theory with single and double excitations (CCSD) with the correlation
      consistent polarized valence double zeta (cc-pVDZ) basis set. The relative
      energies were calculated using the Gaussian-3 second-order Moller-Plesset theory
      with the CCSD/cc-pVDZ geometries. Multireference self-consistent-field and MP2
      methods were also employed using the 6-311G(d,p) and 6-311++G(3df,2p) basis sets.
      Both addition/elimination and direct abstraction mechanisms have been
      investigated. It was revealed that acetylperoxy radical [CH3C(O)OO] is the
      initial adduct and the formation of OH and alpha-lactone [CH2CO2(1A')] is the
      only energetically accessible decomposition channel. The other channels, e.g.,
      abstraction, HO2 + CH2CO, O + CH3CO2, CO + CH3O2, and CO2 + CH3O, are negligible.
      Multichannel Rice-Ramsperger-Kassel-Marcus theory and transition state theory (E
      resolved) were employed to calculate the overall and individual rate coefficients
      and the temperature and pressure dependences. Fairly good agreement between
      theory and experiments has been obtained without any adjustable parameters. It
      was concluded that at pressures below 3 Torr, OH and CH2CO2(1A') are the major
      nascent products of the oxidation of acetyl radicals, although CH2CO2(1A') might
      either undergo unimolecular decomposition to form the final products of CH2O + CO
      or react with OH and Cl to generate H2O and HCl. The acetylperoxy radicals formed
      by collisional stabilization are the major products at the elevated pressures. In
      atmosphere, the yield of acetylperoxy is nearly unity and the contribution of OH
      is only marginal.

PMID- 15974666
TI  - Cavity ringdown spectrum of the forbidden A2E'' <-- X2A(2)' transition of NO3:
      evidence for static Jahn-Teller distortion in the A state.
AB  - The Jahn-Teller effect in the first two excited states of the nitrate radical NO3
      has yet to be experimentally elucidated. In this paper, direct evidence of strong
      Jahn-Teller interactions in the A state is presented from the first complete
      absorption spectrum of the A2E'' <-- X2A(2)' transition of NO3 in the gas phase
      in the region 5900-9000 cm(-1), at moderate resolution (0.15 cm(-1)). The
      observed spectrum is consistent with Herzberg-Teller selection rules, and reveals
      strong linear and quadratic Jahn-Teller interactions in the A state. Several of
      the vibronic bands have been tentatively assigned, including nu2, nu3, an
      irregular progression in nu4, and combination bands involving nu1. Our
      assignments are consistent with the previous works of Weaver et al. [A. Weaver,
      D. W. Arnold, S. E. Bradforth, and D. M. Neumark, J. Chem. Phys. 94, 1740 (1991)]
      and Hirota et al. [E. Hirota, T. Ishiwata, K. Kawaguchi, M. Fujitake, N. Ohashi,
      and I. Tanaka, J. Phys. Chem. 107, 2829 (1997)] The band origin is not observed,
      in accord with the selection rules, but is determined to be T0=7064 cm(-1) from
      the observation of the 4(1)0 hot band at 6695.7 cm(-1). Rotational contour
      analysis of this band indicates that the upper state is an asymmetric rotor,
      establishing that NO3 undergoes static Jahn-Teller distortion in the ground
      vibrational level of the A state.

PMID- 15974667
TI  - An unusual pi* shape resonance in the near-threshold photoionization of S1 para
      difluorobenzene.
AB  - Previously reported dramatic changes in photoelectron angular distributions
      (PADs) as a function of photoelectron kinetic energy following the ionization of
      S1 p-difluorobenzene are shown to be explained by a shape resonance in the b(2g)
      symmetry continuum. The characteristics of this resonance are clearly
      demonstrated by a theoretical multiple-scattering treatment of the
      photoionization dynamics. New experimental data are presented which demonstrate
      an apparent insensitivity of the PADs to both vibrational motion and prepared
      molecular alignment, however, the calculations suggest that strong alignment
      effects may nevertheless be recognized in the detail of the comparison with
      experimental data. The apparent, but unexpected, indifference to vibrational
      excitation is rationalized by considering the nature of the resonance. The
      correlation of this shape resonance in the continuum with a virtual pi*
      antibonding orbital is considered. Because this orbital is characteristic of the
      benzene ring, the existence of similar resonances in related substituted benzenes
      is discussed.

PMID- 15974668
TI  - Ab initio global potential-energy surface for H5(+) --> H3(+) + H2.
AB  - An accurate global potential-energy surface (PES) is reported for H5(+) based on
      more than 100,000 CCSD(T)/aug-cc-pVTZ ab initio energies. This PES has full
      permutational symmetry with respect to interchange of H atoms and dissociates to
      H3(+) and H2. Ten known stationary points of H5(+) are characterized and compared
      to previous ab initio calculations. Quantum diffusion Monte Carlo calculations
      are performed on the PES to obtain the zero-point energy of H5(+) and the
      anharmonic dissociation energy (D0) of H5(+) --> H3(+) + H2. The rigorous zero
      point state of H4D+ is also calculated and discussed within the context of a
      strictly classical approach to obtain the branching ratio of the reaction H4D+ -
      > H3(+) + HD and H2D+ + H2. Such an approach is taken using the PES and critiqued
      based on the properties of the quantum zero-point state. Finally, a simple
      procedure for adding the long range-interaction energy is described.

PMID- 15974669
TI  - Accurate vibrational spectra and magnetic properties of organic free radicals:
      the case of H2CN.
AB  - We present the structural, magnetic, and vibrational properties of H2CN computed
      using a second-order perturbative approach in which equilibrium values and
      harmonic frequencies evaluated at the coupled-cluster level are combined with
      anharmonic and vibrational averaging contributions obtained by hybrid Hartree
      Fock/Kohn-Sham methods. Our computations lead to remarkably accurate results and
      suggest some revision of the experimental vibrational assignments.

PMID- 15974670
TI  - Ab initio studies of two-photon absorption of some stilbenoid chromophores.
AB  - Two-photon absorption of a series of donor-acceptor trans-stilbene derivatives is
      studied by means of density functional theory applied to second-order response
      function. Several important issues in modeling are highlighted which must be
      addressed for a reliable reproduction of the experimental results. It is evident
      that the correct order of magnitude of calculated two-photon absorption cross
      sections can only be obtained if proper account is taken of vibrational
      broadening of the absorption profiles. A comparison of the theoretical results
      with the experimental ones indicates that the computed two-photon absorption
      cross sections are in rough agreement with our previous report, although the
      observed systematic increase of the cross sections with the electron acceptor
      strength is not well reproduced. It is suggested that this disagreement may be
      due not only to the deficiencies of the computations but also to a variety of
      factors contributing to the experimental value of the effective two-photon
      absorption cross section, which are not taken into account in the ab initio
      calculations.

PMID- 15974671
TI  - Accurate ab initio predictions of ionization energies of hydrocarbon radicals:
      CH2, CH3, C2H, C2H3, C2H5, C3H3, and C3H5.
AB  - The ionization energies for methylene (CH2), methyl (CH3), ethynyl (C2H), vinyl
      (C2H3), ethyl (C2H5), propargyl (C3H3), and allyl (C3H5) radicals have been
      calculated by the wave-function-based ab initio CCSD(T)/CBS approach, which
      involves the approximation to the complete basis set (CBS) limit at the coupled
      cluster level with single and double excitations plus a quasiperturbative triple
      excitation [CCSD(T)]. When it is appropriate, the zero-point vibrational energy
      correction, the core-valence electronic correction, the scalar relativistic
      effect correction, the diagonal Born-Oppenheimer correction, and the high-order
      correlation correction have also been made in these calculations. The comparison
      between the computed ionization energy (IE) values and the highly precise
      experimental IE values determined in previous pulsed field ionization
      photoelectron (PFI-PE) studies indicates that the CCSD(T)/CBS method is capable
      of providing accurate IE predictions for these hydrocarbon radicals achieving
      error limits well within +/-10 meV. The benchmarking of the CCSD(T)/CBS IE
      predictions by the PFI-PE experimental results also lends strong support for the
      conclusion that the CCSD(T)/CBS approach with high-level energy corrections can
      serve as a valuable alternative for reliable IE determination of radicals,
      particularly for those radicals with very unfavorable Franck-Condon factors for
      photoionization transitions near their ionization thresholds.

PMID- 15974672
TI  - 18O effects on the infrared spectrum and skeletal tunneling of tropolone.
AB  - Infrared-absorption profiles observed for vibrational transitions of gaseous
      tropolone often show sharp Q branch peaks, some of them ultranarrow spikes,
      indicative of the band origins for vibrational state-specific spectral tunneling
      doublets. In this work oxygen isotope effects for two CH wagging fundamentals,
      the COH torsion fundamental, and the skeletal contortion fundamental are
      reported. They allow considerations to be given: (1) oxygen isotope effects on
      the vibrational frequencies and state-specific tunneling splittings; (2) the
      asymmetry offset of the potential-energy minima for 16O and 18O tropolone; and
      (3) additional details concerning previously proposed high J rotation-contortion
      resonances in the contortional fundamental. The new results help to characterize
      the skeletal contortion fundamental and support the joint participation of
      skeletal tunneling with H tunneling in the vibrational state-specific
      tautomerization processes of tropolone in its ground electronic state.

PMID- 15974673
TI  - Ionic reactions in He nanodroplets: the [LiHHe]+ complex and its possible energy
      pathways into products from ab initio calculations.
AB  - Ab initio calculations at the multiconfiguration self-consistent field level
      followed by a multireference configuration interaction were carried out along the
      two possible collinear approaches of the [LiHHe]+ system, while a three
      dimensional calculation of the structures of that complex with LiH+ kept at its
      equilibrium geometry was also completed at the same level of accuracy. The
      interaction forces of the lowest two electronic states indicate possible reactive
      behavior, with the first excited potential-energy surface clearly showing a
      barrierless path to HeH+ product formation. The details of the reactive pathways
      and their possible bearing on reaction processes, which could occur at the low
      temperature of a He nanodroplet holding LiH+ as an impurity, are analyzed and
      discussed.

PMID- 15974674
TI  - Benchmark calculations of the complete configuration-interaction limit of Born
      Oppenheimer diagonal corrections to the saddle points of isotopomers of the H +
      H2 reaction.
AB  - We present a detailed ab initio study of the effect that the Born-Oppenheimer
      diagonal correction (BODC) has on the saddle-point properties of the H3 system
      and its isotopomers. Benchmark values are presented that are estimated to be
      within 0.1 cm(-1) of the complete configuration-interaction limit. We consider
      the basis set and correlation treatment requirements for accurate BODC
      calculations, and both are observed to be more favorable than for the Born
      Oppenheimer energies. The BODC raises the H + H2 barrier height by 0.1532
      kcal/mol and slightly narrows the barrier--with the imaginary frequency
      increasing by approximately 2%.

PMID- 15974675
TI  - Investigating the breakup dynamics of dihydrogen sulfide ions recombining with
      electrons.
AB  - This paper presents results concerning measurements of the dissociative
      recombination (DR) of dihydrogen sulfide ions. In combination with the ion
      storage ring CRYRING an imaging technique was used to investigate the breakup
      dynamics of the three-body channel in the DR of 32SD2(+). The two energetically
      available product channels S(3P) + 2D(2S) and S(1D) + 2D(2S) were both populated,
      with a branching fraction of the ground-state channel of 0.6(0.1). Information
      about the angle between the two deuterium atoms upon dissociation was obtained
      together with information about how the available kinetic energy was distributed
      between the two light fragments. The recombination cross sections as functions of
      energy in the interval of 1 meV to 0.3 eV in the center-of-mass frame are
      presented for 34SH2(+). The thermal rate coefficient for the DR of 34SH2(+) was
      determined to be (4.8+/-1.0) x 10(-7)(T/300)(-0.72+/-0.1) cm3 s(-1) over this
      interval.

PMID- 15974676
TI  - Time-dependent quantum wave-packet description of the 1pi sigma* photochemistry
      of phenol.
AB  - The photoinduced hydrogen elimination reaction in phenol via the conical
      intersections of the dissociative 1pi sigma* state with the 1pi pi* state and the
      electronic ground state has been investigated by time-dependent quantum wave
      packet calculations. A model including three intersecting electronic potential
      energy surfaces (S0, 1pi sigma*, and 1pi pi*) and two nuclear degrees of freedom
      (OH stretching and OH torsion) has been constructed on the basis of accurate ab
      initio multireference electronic-structure data. The electronic population
      transfer processes at the conical intersections, the branching ratio between the
      two dissociation channels, and their dependence on the initial vibrational levels
      have been investigated by photoexciting phenol from different vibrational levels
      of its ground electronic state. The nonadiabatic transitions between the excited
      states and the ground state occur on a time scale of a few tens of femtoseconds
      if the 1pi pi*-1pi sigma* conical intersection is directly accessible, which
      requires the excitation of at least one quantum of the OH stretching mode in the
      1pi pi* state. It is shown that the node structure, which is imposed on the
      nuclear wave packet by the initial preparation as well as by the transition
      through the first conical intersection (1pi pi*-1pi sigma*), has a profound
      effect on the nonadiabatic dynamics at the second conical intersection (1pi
      sigma*-S0). These findings suggest that laser control of the photodissociation of
      phenol via IR mode-specific excitation of vibrational levels in the electronic
      ground state should be possible.

PMID- 15974677
TI  - Determining the vibrational pattern via overtone cold spectra: C-H methyl
      stretches of propyne.
AB  - Vibrationally mediated photodissociation and photoacoustic (PA) spectroscopy were
      employed for studying the intramolecular dynamics of propyne initially excited to
      the first through fourth overtone of methyl C-H stretching modes. Room
      temperature PA and jet-cooled action spectra, monitoring the absorption of the
      parent and the yield of the ensuing H photofragments, respectively, were
      obtained. The PA spectra exhibit mainly broad features, while the action spectra,
      due to inhomogeneous structure reduction, expose multiple peaks of recognizable
      shapes in the differing overtone manifolds. Symmetric rotor simulations of the
      band contours of the action spectra allowed retrieving of band origins and
      linewidths. The linewidths of the bands in each manifold enabled estimates for
      energy redistribution times out of the corresponding states to the bath states,
      the times ranging from 18+/-6 ps for two quanta of C-H excitation to
      subpicosecond for five quanta. The data were also analyzed in terms of a normal
      mode model and a joint local-/normal-mode model. These models enabled
      determination of harmonic frequencies, anharmonicities, and interaction
      parameters reproducing the observed data in all monitored regions and provided
      spectral assignments. The measured Doppler profiles were well fitted by Gaussians
      with widths suggesting low average translational energies for the released H
      photofragments. These low energies and their similarities to those for
      dissociation of propyne isotopomers preexcited to acetylenic C-H stretches were
      ascribed to an indirect dissociation process occurring after internal conversion
      to the ground electronic state and isomerization to allene.

PMID- 15974678
TI  - Photoelectron spectroscopy of the [glycine x (H2O)(1,2)]- clusters: sequential
      hydration shifts and observation of isomers.
AB  - The electron binding energies of the small hydrated amino acid anions, [glycine x
      (H2O)(1,2)]-, are determined using photoelectron spectroscopy. The vertical
      electron detachment energies (VDEs) are found to increase by approximately 0.12
      eV with each additional water molecule such that the higher electron binding
      isomer of the dihydrate is rather robust, with a VDE value of 0.33 eV. A weak
      binding isomer of the dihydrate is also recovered, however, with a VDE value
      (0.14 eV) lower than that of the monohydrate. Unlike the situation in the smaller
      (n < or = 13) water cluster anions, the [Gly x (H2O)(n > or = 6)]- clusters are
      observed to photodissociate via water monomer evaporation upon photoexcitation in
      the O-H stretching region. We discuss this observation in the context of the
      mechanism responsible for the previously observed [S. Xu, M. Nilles, and K. H.
      Bowen, Jr., J. Chem. Phys. 119, 10696 (2003)] sudden onset in the cluster
      formation at [Gly x (H2O)5]-.

PMID- 15974679
TI  - Laser ablation of NaN3 and CsN3.
AB  - Solid sodium azide and cesium azide crystals were irradiated by high power laser
      pulses; the ablation products were rapidly cooled by a supersonic expansion of
      helium and detected by a time of flight mass spectrometer. Neutral and positively
      charged species were separately recorded and analyzed using 15N isotopomers to
      help in their assignment. Cluster series of the sequences Na(NaN3)n [or
      Cs(CsN3)n] were observed, as well as clusters containing NaOH and NaCN; the
      origin of the C, H, and O atoms appears to be water and CO2 occluded in the salt.
      Addition of D2O increased the intensity of large clusters and added deuterated
      ones, whereas addition of chloroform leads to formation of clusters of a Na atom
      with (NaCl)n clusters. Possible mechanisms for the formation of these clusters
      are discussed.

PMID- 15974680
TI  - On the use of optimal internal vibrational coordinates for symmetrical bent
      triatomic molecules.
AB  - The use of generalized internal coordinates for the variational calculation of
      excited vibrational states of symmetrical bent triatomic molecules is considered
      with applications to the SO2, O3, NO2, and H2O molecules. These coordinates
      depend on two external parameters which can be properly optimized. We propose a
      simple analytical method to determine the optimal internal coordinates for this
      kind of molecules based on the minimization with respect to the external
      parameters of the zero-point energy, assuming only quadratic terms in the
      Hamiltonian and no quadratic coupling between the optimal coordinates. The
      optimal values of the parameters thus obtained are shown to agree quite well with
      those that minimize the sum of a number of unconverged energies of the lowest
      vibrational states, computed variationally using a small basis function set. The
      unconverged variational calculation uses a basis set consisting of the
      eigenfunctions of the uncoupled anharmonic internal coordinate Hamiltonian.
      Variational calculations of the excited vibrational states for the four molecules
      considered carried out with an increasing number of basis functions, also
      evidence the excellent convergence properties of the optimal internal coordinates
      versus those provided by other normal and local coordinate systems.

PMID- 15974681
TI  - Relevance of pi sigma* states in the photoinduced processes of adenine, adenine
      dimer, and adenine-water complexes.
AB  - Ab initio calculations and time-resolved photoionization spectroscopy were
      carried out to characterize the role of the lowest two pi sigma* excited states
      for the photoinduced processes in the adenine monomer, adenine dimer, and adenine
      water clusters. The calculations show--with respect to the monomer--a
      stabilization of 0.11-0.14 eV for the pi sigma* states in different isomers of
      adenine dimer and an even bigger stabilization of 0.14-0.36 eV for isomers of
      adenine-(H2O)1 and adenine-(H2O)3. Hence, the stabilized pi sigma* states should
      play an important role in the excited-state relaxation of partially or fully
      solvated adenine. This conclusion is supported by experimental results: In the
      adenine monomer, strong n pi* state signals are observed. Those signals are
      reduced in adenine dimer and vanish in water clusters due to the competing
      relaxation via the pi sigma* states.

PMID- 15974682
TI  - Radiative association of He+ with H2 at temperatures below 100 K.
AB  - The paper presents a theoretical study of the low-energy dynamics of radiative
      association processes in the He+ + H2 collision system. Formation of the
      triatomic HeH2(+) ion in its bound rotation-vibration states on the potential
      energy surfaces of the ground and of the first excited electronic states is
      investigated. Close-coupling calculations are performed to determine detailed
      state-to-state characteristics (bound <-- free transition rates, radiative and
      dissociative widths of resonances) as well as temperature-average characteristics
      (rate constants, photon emission spectra) of the two-state (X <-- A) reaction
      He+(2S) + H2(X1sigma(g)+) --> HeH2(+)(X2A') + h nu and of the single-state (A <--
      A) reaction He+(2S) + H2(X1sigma(g)+) --> HeH2(+)(A2A') + h nu. The potential
      energy surfaces of the X- and A-electronic states of HeH2(+) and the dipole
      moment surfaces determined ab initio in an earlier work [Kraemer, Spirko, and
      Bludsky, Chem. Phys. 276, 225 (2002)] are used in the calculations. The rate
      constants k(T) as functions of temperature are calculated for the temperature
      interval 1 < or = T < or = 100 K. The maximum k(T) values are predicted as 3.3 x
      10(-15) s(-1) cm3 for the X <-- A reaction and 2.3 x 10(-20) s(-1) cm3 for the A
      <-- A reaction at temperatures around 2 K. Rotationally predissociating states of
      the He+-H2 complex, correlating with the upsilon = 0, j = 2 state of free H2, are
      found to play a crucial role in the dynamics of the association reactions at low
      temperatures; their contribution to the k(T) function of the X <-- A reaction at
      T < 30 K is estimated as larger than 80%. The calculated partial rate constants
      and emission spectra show that in the X <-- A reaction the HeH2(+)(X) ion is
      formed in its highly excited vibrational states. This is in contrast with the
      vibrational state population of the ion when formed via the (X <-- X) reaction
      He(1S) + H2(+)(X2sigma(g)+) --> HeH2(+)(X2A') + h nu.

PMID- 15974683
TI  - Scheme for adding electron-nucleus cusps to Gaussian orbitals.
AB  - A simple scheme is described for introducing the correct cusps at nuclei into
      orbitals obtained from Gaussian basis set electronic structure calculations. The
      scheme is tested with all-electron variational quantum Monte Carlo (VMC) and
      diffusion quantum Monte Carlo (DMC) methods for the Ne atom, the H2 molecule, and
      55 molecules from a standard benchmark set. It greatly reduces the variance of
      the local energy in all cases and slightly improves the variational energy. This
      scheme yields a general improvement in the efficiency of all-electron VMC and DMC
      calculations using Gaussian basis sets.

PMID- 15974684
TI  - Hyper-Rayleigh spectral intensities of gaseous Kr-Xe mixture.
AB  - Binary collision-induced hyper-Rayleigh (CIHR) spectra of Kr-Xe gaseous system
      are computed quantum mechanically and classically within the frequency range up
      to 380 cm(-1). The intensities are expressed in absolute units. The details of
      the theory developed for the CIHR spectra are given and the properties of the
      profiles as well as the depolarization ratio frequency dependence are discussed.
      The contributions to the spectra related to the vector b10(r) and the septor
      b30(r) components of the hyperpolarizability tensor are evaluated.

PMID- 15974685
TI  - Shear viscosity of molten alkali halides from equilibrium and nonequilibrium
      molecular-dynamics simulations.
AB  - The shear viscosity of molten NaCl and KCl was calculated through equilibrium
      (EMD) and nonequilibrium molecular-dynamics (NEMD) simulations in the canonical
      (N,V,T) ensemble. Two rigid-ion potentials were investigated, namely, the Born
      Mayer-Huggins-Tosi-Fumi potential and the Michielsen-Woerlee-Graaf-Ketelaar
      potential with the parameters proposed by Ladd. The NEMD simulations were
      performed using the SLLOD equations of motion [D. J. Evans and G. P. Morriss,
      Phys. Rev. A 30, 1528 (1984)] with a Gaussian isokinetic thermostat and the
      results are compared with those obtained from Green-Kubo EMD (N,V,T) simulations
      and experimental shear viscosity data. The NEMD zero strain rate shear viscosity,
      eta(0), was obtained by fitting a simplified Carreau-type equation and by
      application of mode-coupling theory, i.e., a eta-gamma(1/2) linear relationship.
      The values obtained from the first method are found to be significantly lower
      than those predicted by the second. The agreement between the EMD and NEMD
      results with experimental data is satisfactory for the two potentials
      investigated. The ion-ion radial distribution functions obtained with the two
      rigid-ion potentials for both molten salts are discussed in terms of the
      differences between the two models.

PMID- 15974686
TI  - Overcoming computational uncertainties to reveal chemical sensitivity in single
      molecule conduction calculations.
AB  - In the calculation of conduction through single molecule's approximations about
      the geometry and electronic structure of the system are usually made in order to
      simplify the problem. Previously [G. C. Solomon, J. R. Reimers, and N. S. Hush,
      J. Chem. Phys. 121, 6615 (2004)], we have shown that, in calculations employing
      cluster models for the electrodes, proper treatment of the open-shell nature of
      the clusters is the most important computational feature required to make the
      results sensitive to variations in the structural and chemical features of the
      system. Here, we expand this and establish a general hierarchy of requirements
      involving treatment of geometrical approximations. These approximations are
      categorized into two classes: those associated with finite-dimensional methods
      for representing the semi-infinite electrodes, and those associated with the
      chemisorption topology. We show that ca. 100 unique atoms are required in order
      to properly characterize each electrode: using fewer atoms leads to nonsystematic
      variations in conductivity that can overwhelm the subtler changes. The choice of
      binding site is shown to be the next most important feature, while some effects
      that are difficult to control experimentally concerning the orientations at each
      binding site are actually shown to be insignificant. Verification of this result
      provides a general test for the precision of computational procedures for
      molecular conductivity. Predictions concerning the dependence of conduction on
      substituent and other effects on the central molecule are found to be meaningful
      only when they exceed the uncertainties of the effects associated with binding
      site variation.

PMID- 15974687
TI  - Spin evolution of radical pair with radical containing two groups of equivalent
      magnetic nuclei.
AB  - Analytical solution is obtained for time-resolved magnetic field effects (TR-MFE)
      on recombination fluorescence of radical-ion pair (RIP) containing radical ion
      with two groups of magnetically equivalent nuclei. The present theoretical
      approach is applied to three experimental systems: RIPs containing radical
      cations of 2,3-dimethylbutane, 2,2,6,6-tetramethylpiperidine, or diisopropylamine
      and radical anion of p-terphenyl-d14 in nonpolar alkane solutions. Good agreement
      between theory and experiment is found for all the three systems, hyperfine
      coupling constants of radical cations are obtained by fitting the experimental TR
      MFE traces. The potential of the TR-MFE technique for studying radical ions with
      nonequivalent nuclei is discussed in detail. The wide applicability of the
      theoretical model and the experimental technique make them useful for studying
      short-lived radical species that are often beyond the reach of the conventional
      electron paramagnetic resonance spectroscopy.

PMID- 15974688
TI  - Semiclassical statistical mechanics of hard-body fluid mixtures.
AB  - The thermodynamic properties of semiclassical hard-body fluid mixtures are
      studied. Explicit expressions are given for the free-energy, equation of state
      and virial coefficients of the classical hard convex-body fluid mixtures. The
      numerical results are discussed under different conditions. The agreement with
      the exact data is good in all cases. The first-order quantum corrections are also
      studied. The quantum effects depend on the condition, shape parameters L11* and
      L22*, and concentrations x1 and x2 in general and increase with an increase of
      packing fraction eta, in particular.

PMID- 15974689
TI  - Theoretical study of the effects of solvent environment on photophysical
      properties and electronic structure of paracyclophane chromophores.
AB  - We use first-principles quantum-chemical approaches to study absorption and
      emission properties of recently synthesized distyrylbenzene (DSB) derivative
      chromophores and their dimers (two DSB molecules linked through a
      [2.2]paracyclophane moiety). Several solvent models are applied to model
      experimentally observed shifts and radiative lifetimes in Stokes nonpolar organic
      solvents (toluene) and water. The molecular environment is simulated using the
      implicit solvation models, as well as explicit water molecules and counterions.
      Calculations show that neither implicit nor explicit solvent models are
      sufficient to reproduce experimental observations. The contact pair between the
      chromophore and counterion, on the other hand, is able to reproduce the
      experimental data when a partial screening effect of the solvent is taken into
      account. Based on our simulations we suggest two mechanisms for the excited-state
      lifetime increase in aqueous solutions. These findings may have a number of
      implications for organic light-emitting devices, electronic functionalities of
      soluble polymers and molecular fluorescent labels, and their possible
      applications as biosensors and charge/energy conduits in nanoassemblies.

PMID- 15974690
TI  - Polarizability response in polar solvents: molecular-dynamics simulations of
      acetonitrile and chloroform.
AB  - The relaxation of the many-body polarizability in liquid acetonitrile and
      chloroform at room temperature was studied by molecular-dynamics simulations. The
      collective polarizability induced by intermolecular interactions was included
      using first- and all-orders dipole-induced-dipole models and calculated
      considering both molecule-centered and distributed site polarizabilities. The
      anisotropic response was analyzed using a separation scheme that allows a
      decomposition of the total response in terms of orientational and collision
      induced effects. We found the method effective in approximately separating the
      contributions of these relaxation mechanisms, although the orientational
      collision-induced interference makes a non-negligible contribution to the total
      response. In both liquids the main contribution to the anisotropic response is
      due to orientational dynamics, but intermolecular collision-induced (or
      translational) effects are important, especially at short times. We found that
      higher-order interaction-induced effects were essentially negligible for both
      liquids. Larger differences were found between the center-center and site-site
      models, with the latter showing faster polarizability relaxation and better
      agreement with experiment. Isotropic and anisotropic spectra were computed from
      the corresponding time correlation functions. The lowest-frequency contributions
      are largely suppressed in the isotropic spectra and their overall shape is
      similar to the purely collision-induced contribution to the anisotropic spectra,
      but with an amplitude which is smaller by a factor of approximately 5 in
      acetonitrile and approximately 3 in chloroform.

PMID- 15974691
TI  - A polarizable multistate empirical valence bond model for proton transport in
      aqueous solution.
AB  - A multistate empirical valence bond model for proton transport in water, which
      explicitly includes solvent polarization, is presented. Polarization is included
      for each valence-bond state via induced point dipoles, and the model is
      parametrized to be used with an effective path integral derived potential
      surface, so as to include quantum effects of the transferring proton. The new
      model is shown to reproduce ab initio geometries and energetics for small
      protonated clusters. It is also shown that the new model gives a diffusion
      constant for the excess proton in water, which is in good agreement with
      experiment, and that the qualitative features of ab initio path integral
      simulations [D. Marx, M. E. Tuckerman, J. Hutter, and M. Parrinello, Nature
      (London) 397, 601 (1999)] are well reproduced.

PMID- 15974692
TI  - Investigation of benzene-hexafluorobenzene dynamics in liquid binary mixtures.
AB  - The structure and microscopic dynamics of liquid mixtures of benzene and
      hexafluorobenzene at room temperature and several compositions have been studied
      by molecular-dynamics simulations. In this implementation we have rescaled the
      intermolecular H-F cross potential parameters obtained from the Lorentz-Berthelot
      combining rules, in order to avoid the substantial overestimation of the energy
      of mixing predicted by the model when the usual rules are employed. We found that
      a reduction in the strength of cross H-F interactions by 50% relative to the
      geometric mean is required in order to get a good agreement with experiments.
      Radial-angular pair-correlation functions between like and unlike species have
      been computed and analyzed, by comparing them with the correlations in the
      corresponding neat liquids. We have also studied the microscopic intermolecular
      momentum transfer, by computing the time correlation function between the initial
      velocity of a central molecule and later velocities of neighboring molecules.
      Structural and dynamical information extracted from the mentioned functions seem
      to be consistent with the picture of relatively long-lived benzene
      hexafluorobenzene (Bz-Hf) complexes present in the mixtures, which would be
      responsible for the considerable perturbation of the structure in the first shell
      of like species, and would be moving within the liquid in a parallel face-to-face
      configuration. Using the tools developed originally to estimate hydrogen-bond
      lifetimes in liquids, we have computed the lifetimes of the Bz-Hf complexes as a
      function of the mixture composition, by two different methods: the direct time
      averaging scheme and from the autocorrelation function of bond occupation
      numbers. The obtained lifetimes are strongly dependent on the scheme chosen to
      compute the characteristic times. We have obtained for the Bz-Hf dimer in
      solution, at room temperature, lifetimes in the range of 30-40 ps from averaging
      schemes and around 60-120 ps from autocorrelation function methods. In the latter
      case, the longest times correspond to the equimolar mixture.

PMID- 15974693
TI  - Water models based on a single potential energy surface and different molecular
      degrees of freedom.
AB  - Up to now it has not been possible to neatly assess whether a deficient
      performance of a model is due to poor parametrization of the force field or the
      lack of inclusion of enough molecular properties. This work compares several
      molecular models in the framework of the same force field, which was designed to
      include many-body nonadditive effects: (a) a polarizable and flexible molecule
      with constraints that account for the quantal nature of the vibration [B. Hess,
      H. Saint-Martin, and H. J. C. Berendsen, J. Chem. Phys. 116, 9602 (2002), H.
      Saint-Martin, B. Hess, and H. J. C. Berendsen, J. Chem. Phys. 120, 11133 (2004)],
      (b) a polarizable and classically flexible molecule [H. Saint-Martin, J.
      Hernandez-Cobos, M. I. Bernal-Uruchurtu, I. Ortega-Blake, and H. J. C. Berendsen,
      J. Chem. Phys. 113, 10899 (2000)], (c) a polarizable and rigid molecule, and
      finally (d) a nonpolarizable and rigid molecule. The goal is to determine how
      significant the different molecular properties are. The results indicate that all
      factors--nonadditivity, polarizability, and intramolecular flexibility--are
      important. Still, approximations can be made in order to diminish the
      computational cost of the simulations with a small decrease in the accuracy of
      the predictions, provided that those approximations are counterbalanced by the
      proper inclusion of an effective molecular property, that is, an average
      molecular geometry or an average dipole. Hence instead of building an effective
      force field by parametrizing it in order to reproduce the properties of a
      specific phase, a building approach is proposed that is based on adequately
      restricting the molecular flexibility and/or polarizability of a model potential
      fitted to unimolecular properties, pair interactions, and many-body nonadditive
      contributions. In this manner, the same parental model can be used to simulate
      the same substance under a wide range of thermodynamic conditions. An additional
      advantage of this approach is that, as the force field improves by the quality of
      the molecular calculations, all levels of modeling can be improved.

PMID- 15974694
TI  - Test of classical nucleation theory via molecular-dynamics simulation.
AB  - A direct test of classical nucleation theory (CNT) is made using molecular
      dynamics simulations. The relation between critical nucleus size and undercooling
      temperature is extracted and the result yields the solid-liquid interfacial
      energy. It is shown that the CNT, within the assumptions made for spherical
      nucleus in supercooled liquid, is valid in the critical regime of nucleation for
      a large range of undercooling and nucleus size.

PMID- 15974695
TI  - Nonresonant dielectric hole burning in neat and binary organic glass formers.
AB  - Binary mixtures of the molecular glass former 2-picoline in oligostyrene, in
      which the dielectric response of 2-picoline exhibits a particularly broad
      distribution of correlation times, are investigated by nonresonant dielectric
      hole-burning (NDHB) spectroscopy and the results are compared with NDHB in neat
      systems, in particular, glycerol. It turns out that in both substance classes
      spectral selectivity is achieved, which indicates that dynamics is heterogeneous,
      i.e., slow and fast responses coexist in the material. However, in binary systems
      the position of the spectral modifications is completely determined by the
      spectral density of the pump field, and thus shifts linearly with burn frequency
      as expected, also at pump frequencies around the alpha-relaxation maximum. It is
      shown that in binary systems the lifetime tau(rec) of the spectral modifications
      is determined by the burn frequency omega(p) and exceeds its inverse by about one
      order of magnitude, indicating long-lived dynamic heterogeneity. The data are
      described in terms of a previously suggested model of dynamically selective
      heating, which was extended to include intrinsic nonexponential relaxation. It
      turns out that the spectral broadening in binary mixtures is not only due to
      pronounced dynamic heterogeneity, but partially also due to intrinsic broadening
      of the relaxation function.

PMID- 15974696
TI  - A theoretical investigation of gadolinium (III) solvation in molten salts.
AB  - The solvation of lanthanides [here Gd(III)] in molten LiCl and KCl has been
      studied using a classical solvation approach, based on clusters of increasing
      size. In particular, density-functional calculations have been carried out on
      charged and neutral clusters, containing up to 35 chlorine halide molecules. A
      number of properties have been then evaluated and analyzed, including structural,
      vibrational, and thermochemical data. Special attention has also been devoted to
      the analysis of the local structure of the solvent surrounding the Gd3+ cation, a
      problem deeply investigated by experimentalists. Our results show that the
      charged clusters are not suitable to model the first solvation shell in such
      species, since their structures are strongly affected by the large electrostatic
      contribution. In contrast, more reliable simulations are obtained using the
      neutral clusters. In the latter, the coordination of Gd(III) in molten salts is
      computed to be 8 or 6, according to the salt LiCl or KCl. Furthermore, a good
      agreement is found with the experimental structural data and Raman spectra.
      Finally, preliminary results of potential interest for the estimation of
      solvation thermodynamics, a key parameter for exploiting molten salt chemistry,
      are reported for neutral clusters.

PMID- 15974697
TI  - Layering, condensation, and evaporation of short chains in narrow slit pores.
AB  - The phase behavior of short-chain fluids in slit pores is investigated by using a
      nonlocal-density-functional theory that takes into account the effects of segment
      size, chain connectivity, and van der Waals attractions explicitly. The layering
      and capillary condensation/evaporation transitions are examined at different
      chain length, temperature, pore width, and surface energy. It is found that
      longer chains are more likely to show hysteresis loops and multilayer adsorptions
      along with the capillary condensation and evaporation. Decreasing temperature
      favors the inclusion of layering transitions into the condensation/evaporation
      hysteresis loops. For large pores, the surface energy has relatively small effect
      on the pressures of the capillary condensation and evaporation but affects
      significantly on the layering pressures. It is also observed that all phase
      transitions within the pore take place at pressures lower than the corresponding
      bulk saturation pressure. The critical temperature of condensation/evaporation is
      always smaller than that of the bulk fluid. All coexistence curves for confined
      phase transitions are contained within the corresponding bulk vapor-liquid
      coexistence curve. As in the bulk phase, the longer the chain length, the higher
      are the critical temperatures of phase transitions in the pore.

PMID- 15974698
TI  - Phase transitions in the liquid-vapor interface of dilute alloys of Bi in Ga: new
      experimental studies.
AB  - We report the results of measurements of x-ray reflectivity and grazing incidence
      x-ray diffraction from the liquid-vapor interfaces of four dilute alloys of Bi in
      Ga with mole fractions x(Bi)=0.0032, 0.0023, 0.00037, and 0.000037. The monolayer
      coverage of the alloys with x(Bi)=0.0023, and x(Bi)=0.00037 is about 0.85 and
      only very slightly temperature dependent. The monolayer coverage in the lowest
      concentration alloy, with x(Bi)=0.000037, ranged from 0.82 at 29 degrees C to
      0.58 at 110 degrees C. In none of these alloys, down to the lowest temperature
      used, 29 degrees C, can we find any evidence for crystallization of the Bi
      monolayer that segregates as the outermost stratum of the liquid-vapor interface.
      Drawing on theoretical arguments we propose that the transitions inferred from
      the second-harmonic generation and plasma generation studies of dilute Bi in Ga
      alloys are from the liquid state to the hexatic state of the Bi monolayer. The
      data for the alloy with x(Bi)=0.000037 suggest that near 80 degrees C there is a
      disordered phase-to-disordered phase transition.

PMID- 15974699
TI  - Water adsorption on a p(2x2)-Ni(111)-O surface studied by surface x-ray
      diffraction and infrared reflection absorption spectroscopy at 25 and 140 K.
AB  - The adsorption of water molecules on an oxygen-predosed p(2x2)-Ni(111)-O surface
      was studied by surface x-ray diffraction and infrared reflection absorption
      spectroscopy (IRAS) at temperature of 25 and 140 K. Precise structures including
      adsorbed water, predosed oxygen, and substrate nickel atoms at these two
      temperatures were determined by x-ray structural analysis. It was found that
      water molecules adsorb on oxygen additive sites, forming a hydrogen bond at 25 K.
      A predosed 2x2 oxygen atom appears to accommodate one, two, or three water
      molecules at positions relating to threefold rotation symmetry. When the surface
      temperature was raised to 140 K, water molecules appear at an atop site of Ni.
      The distance between Ni and the oxygen atoms of a monomer water molecule was
      found to be 0.2241(22) nm. The adsorbed water molecule induces buckling and a
      lateral shift of the substrate nickel. The IRAS results provided evidence
      regarding the existence of two distinct adsorption sites. Water molecules in the
      low-temperature phase exhibit bands from both hydrogen-bonded nuOD and free OD
      stretchings, while those in the high-temperature phase lie flat with a molecular
      plane parallel to the surface.

PMID- 15974700
TI  - Absolute electronic excitation cross sections for low-energy electron (5-12 eV)
      scattering from condensed thymine.
AB  - The absolute cross sections for electronic excitations of thymine by electron
      impact between 5 and 12 eV are determined by means of electron-energy loss (EEL)
      spectroscopy for the molecule deposited at submonolayer coverage on an inert Ar
      substrate. The lowest EEL features at 3.7 and 4.0 eV are attributed to the
      excitation of the triplet 1 3A'(pi --> pi*) and 1 3A''(n --> pi*) valence states
      of the molecule. The higher EEL features located at 4.9, 6.3, 7.3, and 9 eV with
      a weak shoulder around 6 eV are ascribed mostly to triplet valence (pi --> pi*)
      excitation manifold of the molecule. The energy dependence of the cross section
      for both the lowest triplet valence excitations shows essentially a peak at about
      5 eV reaching a value of 2.9 x 10(-17) cm2. The cross sections for the higher EEL
      features are generally characterized by a common broad maximum around 8 eV. The
      latter reaches a value of 1.36 x 10(-16) cm2 for the combined 6 and 6.3 eV
      excitation region. The maxima in the present cross sections are found to
      correspond to the resonances that have been reported at about the same energies
      in the O- yield from electron impact on thymine in the gas phase.

PMID- 15974701
TI  - On the convergence of isolated neutral oxygen vacancy and divacancy properties in
      metal oxides using supercell models.
AB  - The properties of isolated neutral oxygen vacancies and divacancies of metal
      oxides of increasing complexity (MgO, CaO, alpha-Al2O3, and ZnO) have been
      studied by means of density-functional theory within a supercell periodic
      approach. Vacancy formation energies, vacancy-vacancy interactions, and geometry
      rearrangements around these point defects have been investigated in detail. The
      characterization of the electronic structure of these point defects has been
      established by analysis of the density of states and of the topology of the
      electron density and of electron localization function. It is found that the
      chemical character of the oxide determines the properties of the oxygen
      vacancies. For the covalent ZnO oxide, a more complex scheme arises in which the
      relaxation around the oxygen vacancy is much larger leading to the formation of
      Zn4-like almost metallic particles in the crystal. The relationship of these
      structures with the crystal shear planes is discussed. The present study shows
      that supercells containing approximately 200-300 atoms provide converged values
      for the geometric and electronic structure of oxygen vacancies of these metal
      oxides in the point defect low concentration limit.

PMID- 15974702
TI  - Theoretical study of single-bubble sonochemistry.
AB  - Numerical simulations of bubble oscillations in liquid water irradiated by an
      ultrasonic wave are performed under the experimental condition for single-bubble
      sonochemistry reported by Didenko and Suslick [Nature (London) 418, 394 (2002)].
      The calculated number of OH radicals dissolving into the surrounding liquid from
      the interior of the bubble agrees sufficiently with the experimental data. OH
      radicals created inside a bubble at the end of the bubble collapse gradually
      dissolve into the surrounding liquid during the contraction phase of an
      ultrasonic wave although about 30% of the total amount of OH radicals that
      dissolve into the liquid in one acoustic cycle dissolve in 0.1 micros at around
      the end of the collapse. The calculated results have indicated that the oxidant
      produced by a bubble is not only OH radical but also O atom and H2O2. It is
      suggested that an appreciable amount of O atom is produced by bubbles inside a
      standing-wave-type sonochemical reactor filled with water in which oxygen is
      dissolved as in the case of air.

PMID- 15974703
TI  - Novel cyanoterphenyl self-assembly monolayers on Au(111) studied by ellipsometry,
      x-ray photoelectron spectroscopy, and vibrational spectroscopies.
AB  - The self-assembled monolayers (SAMs) of two asymmetric disulfides derivatives
      (namely, LC1 and LC2) were prepared on Au(111). The disulfides contain a pure
      alkyl chain and an alkyl chain terminated by a cyanoterphenyl group. LC1 and LC2
      differ by the way the cyanoterphenyl group is attached onto the alkyl chain: it
      is expected to be aligned with the alkyl chain in the case of LC1 and
      perpendicular to it in the case of LC2 (T shape). The consequences in terms of
      surface coverage, chemical composition, and molecular conformation of the two
      SAMs are studied using ellipsometry, x-ray photoelectron spectroscopy (XPS),
      reflection absorption infrared spectroscopy (RAIRS), and broadband femtosecond
      sum-frequency generation (SFG). A model of coverage and tilt angle based on
      ellipsometry and XPS results shows that the SAM "manages" the large size of the
      terphenyl group by lowering the terphenyl containing chain coverage and by
      increasing the tilt. In the case of LC2, the disulfide breaks during molecular
      assembly, less terphenyl chains adsorb than pure alkyl chains, and the overall
      chain coverage is smaller than for LC1. RAIRS and SFG results show that these
      differences in surface coverage correspond to a drastically different orientation
      of the terphenyl axis, which lies nearly parallel to the surface for LC2, while
      it is tilted by approximately 28 degrees for LC1. This shows that the terphenyl
      group takes much more space on the surface in the case of LC2 and explains why
      the terphenyl coverage is found smaller for LC2. The anomalous SFG relative
      intensities observed in the region of CH stretch between CH2 and CH3 modes, and
      symmetric and antisymmetric modes, show that the chains are not in the fully
      stretched, all-trans conformation, LC2 being probably more distorted than LC1.
      These distorsions allow the molecules to occupy the space available below the
      large terphenyl group. The relative intensities of symmetric and antisymmetric
      modes are discussed qualitatively for some typical molecular conformations and
      orientations of the alkyl chain.

PMID- 15974704
TI  - Upconversion luminescence from CdSe nanoparticles.
AB  - Efficient upconversion luminescence has been observed from CdSe nanoparticles
      ranging in size from 2.5 to 6 nm. The upconversion luminescence exhibits a near
      quadratic laser power dependence. Emissions from both excitons and trap states
      are observed in the upconversion and photoluminescence spectra, and in the
      upconversion luminescence the emission from the trap states is enhanced relative
      to the trap-state emission in the photoluminescence. The upconversion decay
      lifetimes are slightly longer than the photoluminescence decay lifetimes. Time
      resolved spectral measurements indicate that this is due to the involvement of
      long decay components from surface or trap states. Both the photoluminescence and
      upconversion luminescence decrease in intensity with increasing temperature due
      mainly to thermal quenching. All the observations indicate that trap states work
      as emitters rather than as intermediate states for upconversion luminescence and
      that two-photon absorption is the likely excitation mechanism.

PMID- 15974705
TI  - Calorimetric study of phase transitions in a liquid-crystal-based microemulsion.
AB  - A lyotropic inverse micelle phase composed of water, thermotropic liquid-crystal
      octylcyanobiphenyl (8CB), and surfactant (DDAB) was studied by using high
      resolution calorimetry on several mixtures with 3%, 8%, and 15% micelle
      concentration. Calorimetric results show strong depression of the isotropic to
      nematic (I-N) phase-transition temperature. Broad heat-capacity anomalies show
      the existence of a wide coexistence range of isotropic, nematic, and smectic-A
      phases, which mimics the behavior of a new nearly stable thermodynamic phase. An
      observation of the rather sharp almost bulklike nematic to smectic-A (N-A)
      transition at low-temperatures indicates that our heat capacity results are
      consistent with the phase separation scenario in which significant number of
      micelles is expelled during I-N conversion leaving almost pure nematic phase at
      lower temperatures. It was found that micelles get almost completely remixed on
      heating the mixture back to the isotropic phase.

PMID- 15974706
TI  - Inverse density-functional theory as an interpretive tool for measuring colloid
      surface interactions in dense systems.
AB  - Recent advances in optical microscopy, such as total internal reflection and
      confocal scanning laser techniques, now permit the direct three-dimensional
      tracking of large numbers of colloidal particles both near and far from
      interfaces. A novel application of this technology, currently being developed by
      one of the authors under the name of diffusing colloidal probe microscopy (DCPM),
      is to use colloidal particles as probes of the energetic characteristics of a
      surface. A major theoretical challenge in implementing DCPM is to obtain the
      potential energy of a single particle in the external field created by the
      surface, from the measured particle trajectories in a dense colloidal system. In
      this paper we develop an approach based on an inversion of density-functional
      theory (DFT), where we calculate the single-particle-surface potential from the
      experimentally measured equilibrium density profile in a nondilute colloidal
      fluid. The underlying DFT formulation is based on the recent work of Zhou and
      Ruckenstein [Zhou and Ruckenstein, J. Chem. Phys. 112, 8079 (2000)]. For model
      hard-sphere and Lennard-Jones systems, using Monte Carlo simulation to provide
      the "experimental" density profiles, we found that the inversion procedure
      reproduces the true particle-surface-potential energy to an accuracy within
      typical DCPM experimental limitations (approximately 0.1 kT) at low to moderate
      colloidal densities. The choice of DFT closures also significantly affects the
      accuracy.

PMID- 15974707
TI  - Morphology changes in the evolution of liquid two-layer films.
AB  - We consider a thin film consisting of two layers of immiscible liquids on a solid
      horizontal (heated) substrate. Both the free liquid-liquid and the liquid-gas
      interface of such a bilayer liquid film may be unstable due to effective
      molecular interactions relevant for ultrathin layers below 100-nm thickness, or
      due to temperature-gradient-caused Marangoni flows in the heated case. Using a
      long-wave approximation, we derive coupled evolution equations for the interface
      profiles for the general nonisothermal situation allowing for slip at the
      substrate. Linear and nonlinear analyses of the short- and long-time film
      evolution are performed for isothermal ultrathin layers, taking into account
      destabilizing long-range and stabilizing short-range molecular interactions. It
      is shown that the initial instability can be of a varicose, zigzag, or mixed
      type. However, in the nonlinear stage of the evolution the mode type, and
      therefore the pattern morphology, can change via switching between two different
      branches of stationary solutions or via coarsening along a single branch.

PMID- 15974708
TI  - Molecular simulation of loading-dependent diffusion in nanoporous materials using
      extended dynamically corrected transition state theory.
AB  - A dynamically corrected transition state theory method is presented that is
      capable of computing quantitatively the self-diffusivity of adsorbed molecules in
      confined systems at nonzero loading. This extension to traditional transition
      state theory is free of additional assumptions and yields a diffusivity identical
      to that obtained by conventional molecular-dynamics simulations. While molecular
      dynamics calculations are limited to relatively fast diffusing molecules, our
      approach extends the range of accessible time scales significantly beyond
      currently available methods. We show results for methane, ethane, and propane in
      LTL- and LTA-type zeolites over a wide range of temperatures and loadings, and
      demonstrate the extensibility of the method to mixtures.

PMID- 15974709
TI  - Molecular-dynamics studies of bending mechanical properties of empty and C60
      filled carbon nanotubes under nanoindentation.
AB  - This paper utilizes molecular-dynamics simulations to investigate the mechanical
      characteristics of a suspended (10, 10) single-walled carbon nanotube (SWCNT)
      during atomic force microscopy (AFM) nanoindentation at different temperatures.
      Spontaneous topological transition of the Stone-Wales (SW) defects is clearly
      observed in the indentation process. The present results indicate that under AFM
      bending deformation, the mechanical properties of the SWCNT, e.g., the bending
      strength, are dependent on the wrapping angle. In addition, it is also found that
      the radial dependence of the reduced formation energy of the SW defects is
      reasonably insensitive only for the small tubes. However, for tube diameters
      greater than 2.4 nm [corresponding to the (18, 18) CNT], the SW defects tend to
      be more radius sensitive. The results indicate that the bending strength
      decreases significantly with increasing temperature. This study also investigates
      the variation in the mechanical properties of the nanotube with the density of
      C60 encapsulated within the nanotube at various temperatures. It is found that,
      at lower temperatures, the bending strength of the C60-filled nanotube increases
      with C60 density. However, the reverse tendency is observed at higher
      temperatures. Finally, the "sharpest tip" phenomena between the probe and the
      tube wall and the elastic recovery of the nanotube during the retraction process
      are also investigated.

PMID- 15974710
TI  - Equation-of-motion coupled-cluster study on exciton states of polyethylene with
      periodic boundary condition.
AB  - Equation-of-motion coupled cluster with singles and doubles (EOM-CCSD) method has
      been applied to exciton states of polyethylene using ab initio crystal Hartree
      Fock method with one-dimensional periodic boundary condition. Full transformation
      of two-electron integrals from atomic-orbital basis to crystal-orbital basis has
      been performed for EOM-CCSD calculations. In order to make transformed integrals
      to have correct properties of translational symmetry, a lattice summation scheme
      has been proposed. The EOM-CCSD excitation energies have been obtained for the
      lowest singlet and triplet exciton states of polyethylene. The excitation
      energies converge with system size much faster than oligomer calculations using n
      alkanes. Quasiparticle energy-level calculations by second-order many-body
      perturbation theory and by solving the inverse Dyson equation have also been
      performed to obtain exciton binding energies. Basis set dependencies on
      excitation energy, quasiparticle band gap, and exciton binding energy have been
      investigated. At the 6-31+G level, the excitation energy of the lowest singlet
      exciton state and its binding energy are calculated to be 8.1 and 3.2 eV,
      respectively. The calculated excitation energy is well comparable with the
      corresponding experimental value, 7.6 eV.

PMID- 15974711
TI  - Density-functional study of model bidisperse ferrocolloids in an external
      magnetic field.
AB  - We present phase diagrams of a model bidisperse ferrocolloid consisting of a
      binary mixture of dipolar hard spheres (DHSs) under the influence of an external
      magnetic field. The dipole moments of the particles are chosen proportional to
      the particle volume to mimic real ferrocolloids, and we focus on dipole-dominated
      systems where isotropic attractive interactions are absent. Our results are based
      on density-functional theory in the modified mean-field (MMF) approximation. For
      one-component DHS fluids in external fields, and for corresponding mixtures
      dominated by one of the components, MMF theory predicts the tricritical point of
      the transition between an isotropic gas and a ferromagnetic liquid occurring at
      zero field to be changed into a critical point separating two magnetically
      ordered phases of different density. The corresponding critical temperature
      displays a nonmonotonic dependence on the field strength. Completely different
      behavior is found for the critical temperature related to the demixing phase
      transitions appearing in strongly asymmetric mixtures [G. M. Range and S. H. L.
      Klapp, Phys. Rev. E 70, 061407 (2004)]. For such systems, we find a monotonic
      decrease of the demixing critical temperature with increasing field. The field
      strength dependence of the critical temperature can therefore be tuned between
      nonmonotonic and monotonic behaviors just by changing the composition of the
      mixture--e.g., by adjusting the chemical potentials. This allows us to
      efficiently control the influence of external magnetic fields on the phase
      behavior over a large temperature interval.

PMID- 15974712
TI  - Arrested phase separation in a short-ranged attractive colloidal system: a
      numerical study.
AB  - We numerically investigate the competition between phase separation and dynamical
      arrest in a colloidal system interacting via a short-ranged attractive potential.
      Equilibrium fluid configurations are quenched at two different temperatures below
      the critical temperature and followed during their time evolution. At the lowest
      studied T, the phase-separation process is interrupted by the formation of an
      attractive glass in the dense phase. At the higher T, no arrest is observed and
      the phase-separation process proceeds endlessly in the simulated time window. The
      final structure of the glass retains memory of the interrupted phase-separation
      process in the form of a frozen spinodal decomposition peak, whose location and
      amplitude is controlled by the average packing fraction. We also discuss the time
      evolution of the nonergodicity parameter, providing evidence of a progressively
      decreasing localization length on increasing the packing fraction. Finally, we
      confirm that the reported results are independent of the microscopic dynamics.

PMID- 15974713
TI  - Ab initio-based exciton model of amide I vibrations in peptides: definition,
      conformational dependence, and transferability.
AB  - Various aspects of the ab initio-based parametrization of an exciton model of
      amide I vibrations in peptides are discussed. Adopting "glycine dipeptide" (Ac
      Gly-NHCH3) as a simple building-block model that describes the vibrational
      interaction between two peptide units, we perform comprehensive quantum-chemical
      calculations to investigate the effect and importance of the level of theory, the
      choice of local coordinates, and the localization method. A solvent continuum
      model description turns out important to obtain planar CONH peptide units when a
      full geometry optimization (which is necessary to obtain the correct frequencies)
      is performed. To study the conformational dependence of the amide I vibrations,
      we calculate (phi,psi) maps of the local-mode frequencies and couplings.
      Performing conformational averages of the (phi,psi) maps with respect to the most
      important peptide conformational states in solution (alpha, beta, P(II), and C5),
      we discuss the relation between these measurable quantities and the corresponding
      conformation of the peptide. Finally, the transferability of these maps to
      dipeptides with hydrophilic and hydrophobic side chains as well as to tripeptides
      with charged end groups is investigated.

PMID- 15974714
TI  - Interpretation of light-scattering spectra in terms of particle displacements.
AB  - Quasielastic light-scattering spectroscopy is regularly used to examine the
      dynamics of dilute solutions of diffusing mesoscopic probe particles in fluids.
      For probes in a simple liquid, the light-scattering spectrum is a simple
      exponential; the field correlation function g(1)(q,tau) of the scattering
      particles is related to their mean-square displacements X2 identical with [(delta
      x(tau))2] during tau via g(1)(q,tau) = exp(-1/2 q2X2). However, demonstrations of
      this expression refer only to identical Brownian particles in simple liquids and
      show that if the form is correct then it is also true for all tau that
      g(1)(q,tau) = exp(-gamma tau), a pure exponential in tau. In general, g(1)(q,tau)
      is not a single exponential in time. A correct general form for g(1)(q,tau) in
      terms of the X(2n), replacing the incorrect exp(-1/2 q2X2), is obtained. A simple
      experimental diagnostic determining when the field correlation function gives the
      mean-square displacement is identified, namely, g(1)(q,tau) only reveals X2 if
      g(1)(q,tau) is a single exponential in tau. Contrariwise, if g(1)(q,tau) is not a
      single exponential, then g(1)(q,tau) depends not only on X2 but on all higher
      moments X(2n). Corrections to the crude approximation g(1)(q,tau) = exp(-1/2
      q2X2) closely resemble the higher spectral cumulants from a cumulant expansion of
      g(1)(q,tau).

PMID- 15974715
TI  - "Glass transition" in peptides: temperature and pressure effects.
AB  - We report on the origin of the liquid-to-glass transition in a series of
      oligopeptides of gamma-benzyl-L-glutamate up to the polymer (PBLG), and in Poly-Z
      L-lysine (PZLL) and Polyglycine (PGly) using dielectric spectroscopy as a
      function of temperature and pressure. We show that temperature is the dominant
      control variable of the dynamics associated with the peptidic "glass transition."
      This is an intrinsic feature of the peptide dynamics, irrespective of the type of
      amino acid and of the peptide secondary structure. The influence of the type of
      secondary structure (alpha helix vs beta sheet) on the liquid-to-glass dynamics
      is discussed.

PMID- 15974717
TI  - Noncollinear magnetic order in the six-atom Mn cluster.

PMID- 15974716
TI  - Rate constants and branching ratios for the dissociative recombination of CO2(+).

PMID- 15974718
TI  - Comment on "Computation of the pseudorotation matrix to satisfy the Eckart axis
      conditions" [J. Chem. Phys. 122, 124103 (2005)].

PMID- 15974722
TI  - Gauge invariance of the spin-other-orbit contribution to the g-tensors of
      electron paramagnetic resonance.
AB  - The spin-other-orbit (SOO) contribution to the g-tensor (DeltagSOO) of electron
      paramagnetic resonance arises due to the interaction of electron-spin magnetic
      moment with the magnetic field produced by the orbital motion of other electrons.
      A similar mechanism is responsible for the leading term in nuclear magnetic
      shielding tensors sigma. We demonstrate that analogous to sigma, paramagnetic
      DeltagSOO contribution exhibits a pronounced dependence on the choice of the
      magnetic-field gauge. The gauge corrections to DeltagSOO are similar in
      magnitude, and opposite in sign, to the paramagnetic SOO term. We calculate gauge
      invariant DeltagSOO values using gauge-including atomic orbitals and density
      functional theory. For organic radicals, complete gauge-invariant DeltagSOO
      values typically amount to less than 500 parts per million (ppm), and are small
      compared to other g-tensor contributions. For the first-row transition-metal
      compounds, DeltagSOO may contribute several thousand ppm to the g-tensor, but are
      negligible compared to the remaining deviations from experiment. With popular
      choices for the magnetic-field gauge, the individual gauge-variant contributions
      may be an order of magnitude higher, and do not provide a reliable estimation of
      DeltagSOO.

PMID- 15974723
TI  - Computation of electrostatic forces between solvated molecules determined by the
      Poisson-Boltzmann equation using a boundary element method.
AB  - A rigorous approach is proposed to calculate the electrostatic forces among an
      arbitrary number of solvated molecules in ionic solution determined by the
      linearized Poisson-Boltzmann equation. The variational principle is used and
      implemented in the frame of a boundary element method (BEM). This approach does
      not require the calculation of the Maxwell stress tensor on the molecular
      surface, therefore it totally avoids the hypersingularity problem in the direct
      BEM whenever one needs to calculate the gradient of the surface potential or the
      stress tensor. This method provides an accurate and efficient way to calculate
      the full intermolecular electrostatic interaction energy and force, which could
      potentially be used in Brownian dynamics simulation of biomolecular association.
      The method has been tested on some simple cases to demonstrate its reliability
      and efficiency, and parts of the results are compared with analytical results and
      with those obtained by some known methods such as adaptive Poisson-Boltzmann
      solver.

PMID- 15974724
TI  - Electron density, exchange-correlation density, and bond characterization from
      the perspective of the valence-bond theory. I. Two simple analytical cases.
AB  - In this work, using a valence-bond wave function we obtain analytical expressions
      for the first- and second-order reduced density matrices of two simple, but quite
      representative, cases of diatomic molecular systems, namely, H2 and LiH. A
      detailed study of their exchange-correlation density is performed for both
      equilibrium and nonequilibrium internuclear distances, discriminating the
      parallel- and antiparallel-spin contributions. The results show that the behavior
      of the exchange-correlation density clearly changes with the character of the
      bond, making it possible to obtain a good deal of information regarding the type
      of the bond interaction.

PMID- 15974725
TI  - Electron density, exchange-correlation density, and bond characterization from
      the perspective of the valence-bond theory. II. Numerical results.
AB  - In this work we have analyzed the bond character of a series of representative
      diatomic molecules, using valence bond and the atoms in molecules points of view.
      This is done using generalized valence-bond calculations. We have also employed
      more exigent levels, as configuration interaction with single and double
      excitations and complete active space self-consistent field calculations, in
      order to validate the generalized valence-bond results. We have explored the
      possibility that the known delocalization index, and a parameter that measures
      the excess or defect population within a given atomic basin, can be considered as
      indicators of the character of bond interaction. We conclude that for a proper
      description of the bond character, the global behavior of both the charge and two
      electron densities should be considered.

PMID- 15974726
TI  - Transport properties of quantum-classical systems.
AB  - Correlation function expressions for calculating transport coefficients for
      quantum-classical systems are derived. The results are obtained by starting with
      quantum transport coefficient expressions and replacing the quantum time
      evolution with quantum-classical Liouville evolution, while retaining the full
      quantum equilibrium structure through the spectral density function. The method
      provides a variety of routes for simulating transport coefficients of mixed
      quantum-classical systems, composed of a quantum subsystem and a classical bath,
      by selecting different but equivalent time evolution schemes of any operator or
      the spectral density. The structure of the spectral density is examined for a
      single harmonic oscillator where exact analytical results can be obtained. The
      utility of the formulation is illustrated by considering the rate constant of an
      activated quantum transfer process that can be described by a many-body bath
      reaction coordinate.

PMID- 15974727
TI  - Nonlinear instability of density-independent orbital-free kinetic-energy
      functionals.
AB  - We study in this article the mathematical properties of a class of orbital-free
      kinetic-energy functionals. We prove that these models are linearly stable but
      nonlinearly unstable, in the sense that the corresponding kinetic-energy
      functionals are not bounded from below. As a matter of illustration, we provide
      an example of an electronic density of simple shape, the kinetic energy of which
      is negative.

PMID- 15974728
TI  - Extension of renormalized coupled-cluster methods including triple excitations to
      excited electronic states of open-shell molecules.
AB  - The general-purpose open-shell implementation of the completely renormalized
      equation-of-motion coupled-cluster approach with singles, doubles, and
      noniterative triples [CR-EOMCCSD(T)] is reported. Benchmark calculations for the
      low-lying doublet and quartet states of the CH radical show that the CR
      EOMCCSD(T) method is capable of providing a highly accurate description of ground
      and excited states of open-shell molecules. This includes states with strong
      double excitation character, for which the conventional EOMCCSD approach fails.

PMID- 15974729
TI  - Characterization of quantum algorithms by quantum process tomography using
      quadrupolar spins in solid-state nuclear magnetic resonance.
AB  - NMR quantum computing with qubit systems represented by nuclear spins (I=12) in
      small molecules in liquids has led to the most successful experimental quantum
      information processors so far. We use the quadrupolar spin-32 sodium nuclei of a
      NaNO3 single crystal as a virtual two-qubit system. The large quadrupolar
      coupling in comparison with the environmental interactions and the usage of
      strongly modulating pulses allow us to manipulate the system fast enough and at
      the same time keeping the decoherence reasonably slow. The experimental challenge
      is to characterize the "calculation" behavior of the quantum processor by process
      tomography which is here adapted to the quadrupolar spin system. The results of a
      selection of quantum gates and algorithms are presented as well as a detailed
      analysis of experimental results.

PMID- 15974730
TI  - Symmetry-adapted perturbation-theory calculations of intermolecular forces
      employing density-functional description of monomers.
AB  - A symmetry-adapted perturbation theory based on Kohn-Sham determinants [SAPT(KS)]
      and utilizing asymptotically corrected exchange-correlation potentials has been
      applied to the He2, Ne2, (H2O)2, and (CO2)2 dimers. It is shown that SAPT(KS) is
      able to recover the electrostatic, first-order exchange, second-order induction,
      and exchange-induction energies with an accuracy approaching and occasionally
      surpassing that of regular SAPT at the currently programmed theory level. The use
      of the asymptotic corrections is critical to achieve this accuracy. The SAPT(KS)
      results can be obtained at a small fraction of the time needed for regular SAPT
      calculations. The robustness of the SAPT(KS) method with respect to the basis set
      size is also demonstrated. A theoretical justification for high accuracy of
      SAPT(KS) predictions for the electrostatic, first-order exchange, and second
      order induction energies has been provided.

PMID- 15974731
TI  - Stochastic potential switching algorithm for Monte Carlo simulations of complex
      systems.
AB  - This paper describes a new Monte Carlo method based on a novel stochastic
      potential switching algorithm. This algorithm enables the equilibrium properties
      of a system with potential V to be computed using a Monte Carlo simulation for a
      system with a possibly less complex stochastically altered potential V. By proper
      choices of the stochastic switching and transition probabilities, it is shown
      that detailed balance can be strictly maintained with respect to the original
      potential V. The validity of the method is illustrated with a simple one
      dimensional example. The method is then generalized to multidimensional systems
      with any additive potential, providing a framework for the design of more
      efficient algorithms to simulate complex systems. A near-critical Lennard-Jones
      fluid with more than 20,000 particles is used to illustrate the method. The new
      algorithm produced a much smaller dynamic scaling exponent compared to the
      Metropolis method and improved sampling efficiency by over an order of magnitude.

PMID- 15974732
TI  - A quantum wave-packet study of intersystem crossing effects in the
      O(3P2,1,0,1D2)+H2 reaction.
AB  - We present for the first time an exact quantum study of spin-orbit-induced
      intersystem crossing effects in the title reaction. The time-dependent wave
      packet method, combined with an extended split operator scheme, is used to
      calculate the fine-structure resolved cross section. The calculation involves
      four electronic potential-energy surfaces of the 1A' state [J. Dobbyn and P. J.
      Knowles, Faraday Discuss. 110, 247 (1998)], the 3A' and the two degenerate 3A"
      states [S. Rogers, D. Wang, A. Kuppermann, and S. Wald, J. Phys. Chem. A 104,
      2308 (2000)], and the spin-orbit couplings between them [B. Maiti, and G. C.
      Schatz, J. Chem. Phys. 119, 12360 (2003)]. Our quantum dynamics calculations
      clearly demonstrate that the spin-orbit coupling between the triplet states of
      different symmetries has the greatest contribution to the intersystem crossing,
      whereas the singlet-triplet coupling is not an important effect. A branch ratio
      of the spin state Pi32 to Pi12 of the product OH was calculated to be
      approximately 2.75, with collision energy higher than 0.6 eV, when the wave
      packet was initially on the triplet surfaces. The quantum calculation agrees
      quantitatively with the previous quasiclassical trajectory surface hopping study.

PMID- 15974733
TI  - Effect of relativity on the ionization spectra of the xenon fluorides XeFn (n=2,
      4, 6).
AB  - Noble gas compounds exhibit special chemical bonding situations and have been
      investigated by various spectroscopic and theoretical techniques. In this work we
      calculate the ionization spectra of the xenon fluorides (XeF2,XeF4, and XeF6) in
      the valence and subvalence (down to Xe 4d) areas by application of the recently
      developed Dirac-Hartree-Fock one-particle propagator technique. In this
      technique, the relativistic (four-component) and electron correlation effects are
      computed simultaneously. The xenon compounds show considerable spin-orbit
      splitting strongly influencing the photoelectron spectrum not reproducible in
      prior calculations. Comparison to one-component methods is made and the occurring
      satellite structures are interpreted. The satellite structures can be attributed
      either to the breakdown of the one-particle picture or to a reflection of intra
      atomic and interatomic Auger decay processes within the molecule.

PMID- 15974734
TI  - Product distributions, rate constants, and mechanisms of LiH+H reactions.
AB  - We present a quantum-mechanical investigation of the LiH depletion reaction LiH+H
      ->Li+H2 and of the H exchange reaction LiH+H'-->LiH'+H. We report product
      distributions, rate constant, and mechanism of the former, and rate constant and
      mechanism of the latter reaction. We use the potential-energy surface by Dunne et
      al. [Chem. Phys. Lett. 336, 1 (2001)], the real-wave-packet method by Gray and
      Balint-Kurti [J. Chem. Phys. 108, 950 (1998)], and the J-shifting approximation.
      The 1H2 nuclear-spin statistics and progressions of vib-rotational states (v',j')
      rule both initial-state-resolved and thermal product distributions, which have
      saw-toothed shapes with odd j' preferred with respect to even j'. At high
      collision energies and temperatures, we obtain a regular 3-to-1 intensity
      alternation of rotational states. At low collision energies and temperatures, the
      degeneracy and density of many H2 levels can, however, give more irregular
      distributions. During the collision, the energy flows from the reactant
      translational mode to the product vibration and recoil ones. The rate constants
      of both reactions are not Arrhenius type because the reactions are barrier-less.
      The low-temperature, LiH depletion rate constant is larger than the H exchange
      one, whereas the contrary holds at high temperature. The real-time mechanisms
      show the nuclear rearrangements of the nonreactive channel and of the reactive
      ones, and point out that the LiH depletion is preferred over the H exchange at
      short times. This confirms the rate-constant results.

PMID- 15974735
TI  - Vibrational raman optical activity as a mean for revealing the helicity of
      oligosilanes: a quantum chemical investigation.
AB  - Using theoretical simulations based on Hartree-Fock and density-functional theory
      calculations, the simulated vibrational Raman optical activity spectra of helical
      conformers of heptasilane are shown to present signatures sensitive to the
      helicity. These signatures are associated with collective wagging, twisting, and
      rocking motions. These simulated spectra have been obtained by combining
      analytical and numerical differentiation procedures to evaluate the geometry
      derivatives of the optical tensors entering into the expressions of the
      vibrational Raman optical activity intensities. From an investigation of basis
      set and electron correlation effects, it is shown that, like for local
      vibrations, diffuse functions are compulsory for evaluating the vibrational Raman
      optical activity intensities of collective vibrational motions.

PMID- 15974736
TI  - On equilibrium structures of the water molecule.
AB  - Equilibrium structures are fundamental entities in molecular sciences. They can
      be inferred from experimental data by complicated inverse procedures which often
      rely on several assumptions, including the Born-Oppenheimer approximation. Theory
      provides a direct route to equilibrium geometries. A recent high-quality ab
      initio semiglobal adiabatic potential-energy surface (PES) of the electronic
      ground state of water, reported by Polyansky et al. [ ibid. 299, 539 (2003)] and
      called CVRQD here, is analyzed in this respect. The equilibrium geometries
      resulting from this direct route are deemed to be of higher accuracy than those
      that can be determined by analyzing experimental data. Detailed investigation of
      the effect of the breakdown of the Born-Oppenheimer approximation suggests that
      the concept of an isotope-independent equilibrium structure holds to about 3 x
      10(-5) A and 0.02 degrees for water. The mass-independent [Born-Oppenheimer (BO)]
      equilibrium bond length and bond angle on the ground electronic state PES of
      water is r(e) (BO)=0.957 82 A and theta e (BO)=104.48(5) degrees , respectively.
      The related mass-dependent (adiabatic) equilibrium bond length and bond angle of
      H2 (16)O is r(e) (ad)=0.957 85 A and theta e (ad)=104.50(0) degrees ,
      respectively, while those of D2 (16)O are r(e) (ad)=0.957 83 A and theta e
      (ad)=104.49(0) degrees . Pure ab initio prediction of J=1 and 2 rotational levels
      on the vibrational ground state by the CVRQD PESs is accurate to better than
      0.002 cm(-1) for all isotopologs of water considered. Elaborate adjustment of the
      CVRQD PESs to reproduce all observed rovibrational transitions to better than
      0.05 cm(-1) (or the lower ones to better than 0.0035 cm(-1)) does not result in
      noticeable changes in the adiabatic equilibrium structure parameters. The
      expectation values of the ground vibrational state rotational constants of the
      water isotopologs, computed in the Eckart frame using the CVRQD PESs and atomic
      masses, deviate from the experimentally measured ones only marginally, especially
      for A0 and B0. The small residual deviations in the effective rotational
      constants are due to centrifugal distortion, electronic, and non-Born-Oppenheimer
      effects. The spectroscopic (nonadiabatic) equilibrium structural parameters of H2
      16O, obtained from experimentally determined A'0 and B'0 rotational constants
      corrected empirically to obtain equilibrium rotational constants, are r(e)
      (sp)=0.957 77 A and theta e (sp)=104.48 degrees .

PMID- 15974737
TI  - Analytic calculation of first-order molecular properties at the explicitly
      correlated second-order Moller-Plesset level: basis-set limits for the molecular
      quadrupole moments of BH and HF.
AB  - The analytic calculation of first-order properties has been implemented in the
      DALTON program at the level of explicitly correlated second-order Moller-Plesset
      perturbation theory (MP2-R12). The implementation has been accomplished for MP2
      R12 theory based on standard approximations A, A', and B, using an auxiliary
      basis for the resolution-of-the-identity approximation, with and without a frozen
      core. MP2-R12 first-order molecular properties have been calculated analytically
      for a few small test molecules. For BH and HF, the MP2-R12 results were
      supplemented with explicitly correlated coupled-cluster calculations (but at this
      level from numerical derivatives) including vibrational and relativistic
      corrections.

PMID- 15974738
TI  - Variation of geometries and electron properties along proton transfer in strong
      hydrogen-bond complexes.
AB  - Proton transfer in hydrogen-bond systems formed by 4-methylimidazole in both
      neutral and protonated cationic forms and by acetate anion are studied by means
      of MP26-311++G(d,p) ab initio calculations. These two complexes model the
      histidine (neutral and protonated)-aspartate diad present in the active sites of
      enzymes the catalytic mechanism of which involves the formation of strong
      hydrogen bonds. We investigate the evolution of geometries, natural bond orbital
      populations of bonds and electron lone pairs, topological descriptors of the
      electron density, and spatial distributions of the electron localization function
      along the process N-H...O-->N...H...O-->N...H-O, which represents the stages of
      the H-transfer. Except for a sudden change in the population of electron lone
      pairs in N and O at the middle N...H...O stage, all the properties analyzed show
      a smooth continuous behavior along the covalent --> hydrogen bond transit
      inherent to the transfer, without any discontinuity that could identify a
      formation or breaking of the hydrogen bond. This way, the distinction between
      covalent or hydrogen-bonding features is associated to subtle electron
      rearrangement at the intermolecular space.

PMID- 15974739
TI  - Magnetically induced current densities in Al4 (2-) and Al4 (4-) species studied
      at the coupled-cluster level.
AB  - Magnetically induced current densities in the four-membered rings of Al4(2-) and
      Al4(4-) species have been calculated at the coupled-cluster singles and doubles
      (CCSD) level by applying the recently developed gauge-including magnetically
      induced current (GIMIC) method. The strength of the ring-current susceptibilities
      were obtained by numerical integration of the current densities passing through a
      cross section perpendicular to the Al4 ring. The GIMIC calculations support the
      earlier notion that Al4 (2-) with formally two pi electrons sustains a net
      diatropic ring current. The diatropic contribution to the ring-current
      susceptibility is carried by the electrons in both the sigma (16.7 nAT) and the
      pi (11.3 nAT) orbitals. The induced ring current in the Al4 (4-) compounds, with
      four pi electrons, consists of about equally strong diatropic sigma and
      paratropic pi currents of about 14 and -17 nAT, respectively. The net current
      susceptibilities obtained for Al4Li-, Al4Li2, Al4Li3(-), and Al4Li4 at the CCSD
      level using a triple-zeta basis set augmented with polarization functions are
      28.1, 28.1, -5.9, and -3.1 nAT, respectively. The corresponding diatropic
      (paratropic) contributions to the ring-current susceptibilities are 32.4 (0.0),
      36.7 (0.0), 18.9 (-19.9), and 18.6 (-16.8) nAT, respectively. For the Al4(2-) and
      Al4(4-) species, the net currents circling each Li+ cation is estimated to 4.3
      and 2.4 nAT, respectively.

PMID- 15974740
TI  - Addition of water, methanol, and ammonia to Al3O3- clusters: reaction products,
      transition states, and electron detachment energies.
AB  - Products of reactions between the book and kite isomers of Al3O3- and three
      important molecules are studied with electronic structure calculations.
      Dissociative adsorption of H2O or CH3OH is highly exothermic and proton-transfer
      barriers between anion-molecule complexes and the products of these reactions are
      low. For NH3, the reaction energies are less exothermic and the corresponding
      barriers are higher. Depending on experimental conditions, Al3O3- (NH3)
      coordination complexes or products of dissociative adsorption may be prepared.
      Vertical electron detachment energies of stable anions are predicted with ab
      initio electron propagator calculations and are in close agreement with
      experiments on Al3O3- and its products with H2O and CH3OH. Changes in the
      localization properties of two Al-centered Dyson orbitals account for the
      differences between the photoelectron spectra of Al3O3- and those of the product
      anions.

PMID- 15974741
TI  - Microwave spectra of the Xe-N2 van der Waals complex: a comparison of experiment
      and theory.
AB  - Rotational transitions for the Xe-N2 complex were measured in the frequency
      region from 4 to 18 GHz using a pulsed-nozzle Fourier-transform microwave
      spectrometer. Twelve (four) a-type transitions were recorded for the 132Xe-14N2
      and 129Xe-14N2 (131Xe-15N)) isotopomers. In addition, the nuclear quadrupole
      hyperfine structures due to the presence of the 14N (nuclear-spin quantum number
      I=1) and 131Xe (I=32) nuclei were detected and analyzed. Two ab initio potential
      energy surfaces were calculated at the coupled-cluster level of theory with
      single, double, and pertubatively included triple excitations. Dunning's
      augmented correlation-consistent polarized valence triple-zeta basis set was used
      for the nitrogen atoms. For the first surface, a well-tempered basis set with
      additional polarization functions was used for the Xe atom; for the second
      surface, a newly developed augmented correlation-consistent polarized valence
      quintuple-zeta basis set employing small-core relativistic pseudopotentials was
      used for the Xe atom. The basis sets were supplemented with bond functions for
      the van der Waals bond. The counterpoise correction was applied to reduce the
      basis-set superposition error. The resulting two surfaces both have a single
      minimum at a T-shaped geometry, with well depths of 122.4 and 119.3 cm(-1),
      respectively. Bound-state energies supported by the potential-energy surface were
      determined. The quality of the ab initio potential-energy surfaces was evaluated
      by comparison of the experimental transition frequencies and rotational and
      centrifugal distortion constants with those derived from the bound-state
      energies. A scaled potential-energy surface was obtained which has excellent
      agreement with the experimental data.

PMID- 15974742
TI  - Direct measurement of the energy thresholds to conformational isomerization in
      tryptamine: experiment and theory.
AB  - The methods of stimulated emission pumping-hole filling spectroscopy (SEP-HFS)
      and stimulated emission pumping population transfer spectroscopy (SEP-PTS) were
      applied to the conformation-specific study of conformational isomerization in
      tryptamine [TRA, 3-(2-aminoethyl)indole]. These experimental methods employ
      stimulated emission pumping to selectively excite a fraction of the population of
      a single conformation of TRA to well-defined ground-state vibrational levels.
      This produces single conformations with well-defined internal energy, tunable
      over a range of energies from near the zero-point level to well above the lowest
      barriers to conformational isomerization. When the SEP step overcomes a barrier
      to isomerization, a fraction of the excited population isomerizes to form that
      product. By carrying out SEP excitation early in a supersonic expansion, these
      product molecules are subsequently cooled to their zero-point vibrational levels,
      where they can be detected downstream with a third tunable laser that probes the
      ground-state population of a particular product conformer via a unique
      ultraviolet transition using laser-induced fluorescence. The population transfer
      spectra (recorded by tuning the SEP dump laser while holding the pump and probe
      lasers fixed) exhibit sharp onsets that directly determine the energy thresholds
      for conformational isomerization in a given reactant-product conformer pair. In
      the absence of tunneling effects, the first observed transition in a given X-Y
      PTS constitutes an upper bound to the energy barrier to conformational
      isomerization, while the last transition not observed constitutes a lower bound.
      The bounds for isomerizing conformer A of tryptamine to B(688-748 cm(-1)),
      C(1)(860-1000 cm(-1)), C(2)(1219-1316 cm(-1)), D(1219-1282 cm(-1)), E(1219-1316
      cm(-1)), and F(688-748 cm(-1)) are determined. In addition, thresholds for
      isomerizing from B to A(<1562 cm(-1)), B to F(562-688 cm(-1)), and out of C(2) to
      B(<747 cm(-1)) are also determined. The A-->B and B-->A transitions are used to
      place bounds on the relative energies of minima B relative to A, with B lying at
      least 126 cm(-1) above A. The corresponding barriers have been computed using
      both density functional and second-order many-body perturbation theory methods in
      order to establish the level of theory needed to reproduce experimental results.
      While most of the computed barriers match experiment well, the barriers for the A
      F and B-F transitions are too high by almost a factor of 2. Possible reasons for
      this discrepancy are discussed.

PMID- 15974743
TI  - Direct measurement of the energy thresholds to conformational isomerization. II.
      3-indole-propionic acid and its water-containing complex.
AB  - The methods of stimulated emission pumping-hole-filling spectroscopy (SEP-HFS)
      and population transfer spectroscopy (SEP-PTS) were used to place direct
      experimental bounds on the energetic barriers to conformational isomerization in
      3-indole-propionic acid (IPA) and its water-containing complex. By contrast with
      tryptamine (Paper I), IPA has only two conformations with significant population
      in them. The structures of the two conformers are known from previous work [P. M.
      Felker, J. Phys. Chem. 96, 7844 (1992)]. The energy thresholds for A-->B and B-
      >A isomerizations are placed at 854 and 754 cm(-1), respectively. Lower bounds on
      the isomerization barrier in the two directions are determined from the last
      transition not observed in the SEP-PT spectra. These are placed at 800 and 644
      cm(-1) for A-->B and B-->A, respectively. The combined results place bounds on
      the relative energies of the A and B minima, with E(B)-E(A)=46-210 cm(-1). Like
      the IPA monomer, the IPA-H2O complex forms two conformational isomers. Both these
      isomers incorporate the water molecule as a bridge between the carbonyl and OH
      groups of the carboxylic acid. Previous rotational coherence measurements (L. L.
      Connell, Ph.D. thesis, UCLA, 1991) have determined that these complexes retain
      the same IPA conformational structure as the monomers. SEP-PTS and SEP-HFS were
      carried out on the IPA-H2O complexes. It was demonstrated that it is possible to
      use SEP to drive conformational isomerization between the two conformational
      isomers of IPA-H2O. Bounds on the energy barriers to conformational isomerization
      are not effected greatly by the presence of the water molecule, with Ebarrier(A-
      >B)=771-830 cm(-1) and Ebarrier(B-->A)=583-750 cm(-1). This is a simple
      consequence of the fact that the barrier is an intramolecular barrier, and the
      water molecule is held fixed in the COOH pocket, where it interacts with the ring
      only peripherally during the isomerization process. Finally, changes in the SEP
      PT spectral intensity in transitions near the top of the barrier to isomerization
      as a function of the position of SEP excitation relative to the pulsed valve exit
      provide some insight to the competition between vibrational relaxation and
      isomerization in a molecule the size of IPA.

PMID- 15974744
TI  - Rydberg electron transfer to SF6: product ion lifetimes.
AB  - The lifetimes of SF6- ions produced by Rydberg electron transfer in K(np)SF6
      collisions at high n, n greater or similar to 30, are examined using a Penning
      ion trap. The data point to the formation of ions with a range of lifetimes that
      extends from approximately 1 to greater or similar to 10 ms. Sizable numbers of
      ions remain in the trap even 40 ms after initial injection and at least part of
      this signal can be attributed to radiative stabilization. Measurements of free
      low-energy electron attachment to SF6 in the trap show that the product ions have
      lifetimes similar to those of SF6- ions formed by electron transfer in high-n
      collisions.

PMID- 15974745
TI  - Fourier transform microwave spectroscopy of HSiBr: exploring the Si-Br bond
      through quadrupole hyperfine coupling.
AB  - The 1(01)-0(00) (9-10 GHz) and 2(02)-1(01) (18-19 GHz) rotational transitions of
      HSi 79Br and HSi 81Br have been measured in a pulsed discharge jet expansion to
      an experimental uncertainty of approximately 1 kHz using Fourier transform
      microwave spectroscopy. The data have yielded an effective rotational constant,
      the centrifugal distortion constant Dj, the bromine nuclear quadrupole coupling
      constants, and the bromine nuclear spin-molecular rotation interaction parameter
      for both isotopomers. The derived parameters have been compared to their values
      calculated ab initio, and the nuclear quadrupole coupling tensor has been used to
      investigate the Si-Br bond, giving a sigma bond ionic character of 0.60, a pi
      bond character of 0.22, and a total Si-Br ionic character of 0.38. These bond
      characteristics have been compared to trends in other halosilylenes, silanes, and
      the analogous carbenes.

PMID- 15974746
TI  - Theoretical study of the electronic structure of the lower states of the
      [Cr2Cl9]3- and [Mo2Cl9]3- ions.
AB  - The electronic structure of the lower states of a trigonal Cr3+ pair and Mo3+
      pair, which occur in the Cs3M2Cl9 crystal (M=Cr,Mo), were studied by theoretical
      calculations carried out according to several methods: multireference singly and
      doubly excited configuration interaction, second-order configuration interaction,
      and multireference coupled-pair approximation. We employed a model of a [M2Cl9]3-
      anion embedded in a cage of point charges, which were arranged so as to simulate
      the anion in the crystal. The model core potential was utilized, where the
      relativistic effect was included for Mo. Results of the Cr complex showed that
      there were no direct bonds between the Cr metals. The lower electronic spectra of
      the [Cr2Cl9]3- ion were interpreted in terms of the electronic spectra of
      [CrCl6]3-. The lowest state of simultaneous excitation in both metals was
      considered. The [Mo2Cl9]3- ion exhibited a single direct bond between the metals.
      Reflecting this single bond, the observed singlet-triplet splitting was much
      larger than that in the case of Cr and the calculated splitting was in good
      agreement with the observed one. We account for the electronic spectra of the
      [Mo2Cl9]3- complex, which exhibited quite different features in the electronic
      excitation spectra in comparison with those of the Cr complex.

PMID- 15974747
TI  - Pulsed-field ionization electron spectroscopy and conformation of copper
      diammonia.
AB  - Copper-diammonia, Cu(NH3)2, and its deuterated species, Cu(ND3)2, are produced in
      supersonic molecular beams and studied by pulsed-field ionization zero electron
      kinetic energy photoelectron spectroscopy and ab initio calculations. Structural
      isomers with a copper atom binding to an ammonia dimer or two ammonia molecules
      are obtained by the calculations. By comparing the experimental measurements to
      the theoretical calculations, the neutral and ionic forms of copper-diammonia are
      determined to be in a doubly bound linear conformation in their ground electronic
      states. The adiabatic ionization potentials of Cu(NH3)2 and Cu(ND3)2 are measured
      as 29,532 (5) and 29,313 (5) cm(-1), respectively. The metal-ligand symmetric
      stretching frequencies are measured to be 436 cm(-1) for Cu+-(NH3)2 and 398 cm(
      1) for Cu+-(ND3)2, and the metal-ligand bending frequencies 75,139 cm(-1) for
      CuCu+-(NH3)2 and 70125 cm(-1) for CuCu+-(ND3)2. Moreover, the dissociation energy
      of Cu(NH3)2-->CuNH3+NH3 is determined to be 11(3) kcal mol(-1) through a
      thermodynamic relationship.

PMID- 15974748
TI  - Shell and subshell periodic structures of icosahedral nickel nanoclusters.
AB  - Using the modified analytic embedded atom method and molecular dynamics, the
      binding energies and their second order finite differences (stability functions)
      of icosahedral Ni clusters with shell and subshell periodicity are studied in
      detail via atomic evolution. The results exhibit shell and subshell structures of
      the clusters with atoms from 147 to 250,000, and the atomic numbers corresponding
      to shell or subshell structures are in good agreement with the experimental magic
      numbers obtained in time-of-flight mass spectra of threshold photoionization, and
      Martin's theoretical proposition of progressive formation of atomic umbrellas.
      Clusters with size from 147 to 561 atoms are energetically investigated via one
      by-one atomic evolution and their magic numbers are theoretically proved. For
      medium-size Ni clusters with 561 to 2057 atoms, the prediction of magic numbers
      with atomic numbers is performed on the basis of umbrella-like subshell growth in
      near face-edge-vertex order. The similarity of the energy curves makes it
      possible to extend the prediction to even larger Ni nanoclusters in hierarchical
      Mackay icosahedral configurations.

PMID- 15974749
TI  - General methods for free-volume theory.
AB  - Free-volume theory for understanding depletion phenomena in mixtures of two
      species is generally derived using scaled-particle theory for those specific
      entities. Here we first give a general scaled-particle method for convex bodies
      in terms of the characteristic geometrical measures of the depletion agent, i.e.,
      its volume, surface area, and integrated mean curvature, in mixtures with hard
      spheres. Second, we show that similar results can be derived from fundamental
      measure theory. This different approach allows us to get a deep insight into the
      meaning of the various contributions to the theory from a geometrical point of
      view. From these two methods we arrive at a generalized "recipe" to free-volume
      theory. This recipe can be based on a desired equation of state for any convex
      shape of the depletion agents and is also valid for (polydisperse) mixtures of
      those. This is illustrated by mixtures of spheres with ellipsoids, spheres with
      several geometries as models for disklike mesogens, e.g., gibbsite, as well as
      depletion of spheres due to bar-shaped colloids, e.g., goethite.

PMID- 15974750
TI  - Soluble stochastic dynamics of quasi-one-dimensional single-file fluid self
      diffusion.
AB  - We solve a model of random-walk stochastic dynamics for hard single-file fluids
      in the experimentally important quasi-one-dimensional regime. This is a
      nontrivial extension of exact solution beyond one dimension. We point out that
      quasi-one-dimensional single-file self-diffusion of one-component hard fluids of
      diameter a under stochastic forces is equivalent at long time to a one
      dimensional hard-rod fluid with the same linear density but a different diameter,
      a(eff). This effective diameter is controlled by the details of the relative
      dynamics between the transverse and longitudinal directions. There are two
      regimes of limiting behavior. For very fast transverse motion, the system is
      likely (but we cannot prove rigorously) to be equivalent to the soluble-oriented
      hard-rectangle or cylinder systems, with a(eff)=a. With very slow transverse
      motion, the self-diffusion dynamics is described by an equivalent soluble one
      dimensional mixture of fluids with a(eff)=a(ave), the average longitudinal
      separation between nearest-neighbor particles at contact. We have explored our
      theoretical predictions with Monte Carlo simulations.

PMID- 15974751
TI  - The gas-liquid phase-transition singularities in the framework of the liquid
      state integral equation formalism.
AB  - The singularities of various liquid-state integral equations derived from the
      Ornstein-Zernike relation and its temperature derivatives, have been investigated
      in the liquid-vapor transition region. As a general feature, it has been found
      that the existence of a nonsolution curve on the vapor side of the phase diagram,
      on which both the direct and the total correlation functions become complex-with
      a finite isothermal compressibility-also corresponds to the locus of points where
      the constant-volume heat capacity diverges, in consonance with a divergence of
      the temperature derivative of the correlation functions. In contrast, on the
      liquid side of the phase diagram one finds that a true spinodal (a curve of
      diverging isothermal compressibilities) is reproduced by the Percus-Yevick and
      Martynov-Sarkisov integral equations, but now this curve corresponds to states
      with finite heat capacity. On the other hand, the hypernetted chain approximation
      exhibits a nonsolution curve with finite compressibilities and heat capacities in
      which, as temperature is lowered, the former tends to diverge.

PMID- 15974752
TI  - Theory of long-lived nuclear spin states in solution nuclear magnetic resonance.
      I. Singlet states in low magnetic field.
AB  - We have recently demonstrated the existence of exceptionally long-lived nuclear
      spin states in solution-state nuclear magnetic resonance. The lifetime of nuclear
      spin singlet states in systems containing coupled pairs of spins-12 may exceed
      the conventional relaxation time constant T1 by more than an order of magnitude.
      These long lifetimes may be observed if the long-lived singlet states are
      prevented from mixing with rapidly relaxing triplet states. In this paper we
      provide the detailed theory of an experiment which uses magnetic field cycling to
      observe slow singlet relaxation. An approximate expression is given for the
      magnetic field dependence of the singlet relaxation rate constant, using a model
      of intramolecular dipole-dipole couplings and fluctuating external random fields.

PMID- 15974753
TI  - Homogeneous nucleation rate measurements of 1-butanol in helium: a comparative
      study of a thermal diffusion cloud chamber and a laminar flow diffusion chamber.
AB  - Isothermal homogeneous nucleation rates of 1-butanol were measured both in a
      thermal diffusion cloud chamber and in a laminar flow diffusion chamber built
      recently at the Institute of Chemical Process Fundamentals, Academy of Sciences
      of the Czech Republic, Prague, Czech Republic. The chosen system 1-butanol-helium
      can be studied reasonably well in both devices, in the overlapping range of
      temperatures. The results were compared with those found in the literature and
      those measured by Lihavainen in a laminar flow diffusion chamber of a similar
      design. The same isotherms measured with the thermal diffusion cloud chamber
      occur at highest saturation ratios of the three devices. Isotherms measured with
      the two laminar flow diffusion chambers are reasonably close together; the
      measurements by Lihavainen occur at lowest saturation ratios. The temperature
      dependences observed were similar in all three devices. The molecular content of
      critical clusters was calculated using the nucleation theorem and compared with
      the Kelvin equation. Both laminar flow diffusion chambers provided very similar
      sizes slightly above the Kelvin equation, whereas the thermal diffusion cloud
      chamber suggests critical cluster sizes significantly smaller. The results found
      elsewhere in the literature were in reasonable agreement with our results.

PMID- 15974754
TI  - An optimized molecular potential for carbon dioxide.
AB  - An optimized molecular potential model for carbon dioxide is presented in this
      paper. Utilizing the established techniques of molecular-dynamics and histogram
      reweighting grand canonical Monte Carlo simulations, this model is demonstrated
      to show excellent predictability for thermodynamic, transport, and liquid
      structural properties in a wide temperature-pressure range with remarkable
      accuracies. The average deviations of this new model from experimental data for
      the saturated liquid densities, vapor densities, vapor pressures, and heats of
      vaporization are around 0.1%, 2.3%, 0.7%, and 1.9%, respectively. The calculated
      critical point is almost pinpointed by the new model. The experimental radial
      distribution functions ranging from 240.0 to 473.0 K are well reproduced as
      compared to neutron-diffraction measurements. The predicted self-diffusion
      coefficients are in good agreement with the nuclear-magnetic-resonance
      measurements. The previously published potential models for CO2 are also
      systematically evaluated, and our proposed new model is found to be superior to
      the previous models in general.

PMID- 15974755
TI  - Decomposing total IR spectra of aqueous systems into solute and solvent
      contributions: a computational approach using maximally localized Wannier
      orbitals.
AB  - The theoretical principles underpinning the calculation of infrared spectra for
      condensed-phase systems in the context of ab initio molecular dynamics have been
      recently developed in literature. At present, most ab initio molecular dynamics
      calculations are restricted to relatively small systems and short simulation
      times. In this paper we devise a method that allows well-converged results for
      infrared spectra from ab initio molecular dynamics simulations using small
      systems and short trajectories characteristic of simulations typically performed
      in practice. We demonstrate the utility of our approach by computing the
      imaginary part of the dielectric constant epsilon"(omega) for H2O and D2O in
      solid and liquid phases and show that it compares well with experimental data. We
      further demonstrate that maximally localized Wannier orbitals can be used to
      separate the individual contributions of different molecular species to the
      linear spectrum of complex systems. The new spectral decomposition method is
      shown to be useful in present-day ab initio molecular dynamics calculations to
      compute the magnitude of the "continuous absorption" generated by excess protons
      in aqueous solutions with good accuracy even when other species present in the
      solutions absorb strongly in the same frequency window.

PMID- 15974756
TI  - Spatiotemporal patterns driven by autocatalytic internal reaction noise.
AB  - The influence that intrinsic local-density fluctuations can have on solutions of
      mean-field reaction-diffusion models is investigated numerically by means of the
      spatial patterns arising from two species that react and diffuse in the presence
      of strong internal reaction noise. The dynamics of the Gray-Scott (GS) model [P.
      Gray and S. K. Scott, Chem. Eng. Sci. 38, 29 (1983); and ibid.39, 1087 (1984);
      and J. Phys. Chem. 89, 22 (1985)] with a constant external source is first cast
      in terms of a continuum field theory representing the corresponding master
      equation. We then derive a Langevin description of the field theory and use these
      stochastic differential equations in our simulations. The nature of the
      multiplicative noise is specified exactly without recourse to assumptions and
      turns out to be of the same order as the reaction itself, and thus cannot be
      treated as a small perturbation. Many of the complex patterns obtained in the
      absence of noise for the GS model are completely obliterated by these strong
      internal fluctuations, but we find novel spatial patterns induced by this
      reaction noise in the regions of parameter space that otherwise correspond to
      homogeneous solutions when fluctuations are not included.

PMID- 15974757
TI  - Transport of a liquid water and methanol mixture through carbon nanotubes under a
      chemical potential gradient.
AB  - In this work, we report a dual-control-volume grand canonical molecular dynamics
      simulation study of the transport of a water and methanol mixture under a fixed
      concentration gradient through nanotubes of various diameters and surface
      chemistries. Methanol and water are selected as fluid molecules since water
      represents a strongly polar molecule while methanol is intermediate between
      nonpolar and strongly polar molecules. Carboxyl acid (-COOH) groups are anchored
      onto the inner wall of a carbon nanotube to alter the hydrophobic surface into a
      hydrophilic one. Results show that the transport of the mixture through
      hydrophilic tubes is faster than through hydrophobic nanotubes although the
      diffusion of the mixture is slower inside hydrophilic than hydrophobic pores due
      to a hydrogen network. Thus, the transport of the liquid mixture through the
      nanotubes is controlled by the pore entrance effect for which hydrogen bonding
      plays an important role.

PMID- 15974758
TI  - Analysis of conducting-system frequency response data for an interfacial
      amorphous phase of copper-core oxide-shell nanocomposites.
AB  - Complex electrical-conductivity experimental data sets for the interfacial
      amorphous phase in copper-core-copper-oxide-shell nanostructured composites have
      been analyzed using two Kohlrausch-related frequency response models recently
      developed for analysis of the dispersive electrical response of conductive
      materials. Such analysis has been carried out for both the precursor (herein
      referred to as the reference) glass as well as the glass in which the core-shell
      nanostructure was developed after suitable heat treatment. Complex nonlinear
      least-squares data fitting at each temperature employed composite Kohlrausch
      models that included electrode effects. Because of the lack of sufficient high
      frequency data, it was necessary to use fixed, rather than free, values of the
      shape parameter beta1 of the model. On the basis of topological considerations,
      its values were set at 13 and 23 for the reference glass and the core-shell
      structured glass, respectively. The activation energies of resistivity for the
      reference and the treated glasses were found to have values of about 2 and 0.4
      eV, respectively, indicating two different mechanisms of electrical conduction. A
      blocking-electrode measurement on the reference glass indicated the presence of
      an electronic as well as an ionic component of the electrical conductivity, with
      the ionic part dominating at the temperatures for which the present analyses were
      carried out.

PMID- 15974759
TI  - Low-temperature epitaxial Ni silicidation: the role of hyperthermal species.
AB  - We present the results of Ni silicidation on a Si111 surface employing a mass
      selected hyperthermal ion beam at 100 eV and discuss the reaction mechanism
      compared with the conventional Ni silicidation process. It is found that the Ni
      silicide formation using this technique is different from that achieved by
      conventional methods such as high-energy Ni-ion implantation or evaporation with
      thermal species. Namely, the Ni silicide phase formed at 230 degrees C using
      hyperthermal ions in this study is Ni-rich Ni2Si, in contrast to Si-rich
      disilicide NiSi2, ordinarily formed when high-energy Ni ions or thermal Ni beams
      react with Si at elevated temperatures. In addition, this layer is formed
      epitaxially on Si in spite of a low substrate temperature of 230 degrees C, while
      a polycrystalline Ni silicide layer is formed with conventional Ni-rich
      silicidation. This suggests that the reaction mechanism of the silicide formation
      with hyperthermal Ni particles is different from that using higher- or thermal
      energy Ni particles. The atomic rearrangement induced by the thermal spikes most
      likely plays an important role in the Ni silicidation process employing
      hyperthermal species.

PMID- 15974760
TI  - Relaxation of hot atoms following H2 dissociation on a Pd111 surface.
AB  - We study the relaxation of hot H atoms produced by dissociation of H2 molecules
      on the Pd111 surface. Ab initio density-functional theory calculations and the
      "corrugation reducing procedure" are used to determine the interaction potential
      for a H atom in front of a rigid surface as well as its modification under
      surface-atom vibrations. A slab of 80 Pd atoms is used to model the surface
      together with "generalized Langevin oscillators" to account for energy
      dissipation to the bulk. We show that the energy relaxation is fast, about 75% of
      the available energy being lost by the hot atoms after 0.5 ps. As a consequence,
      the hot atoms do not travel more than a few angstroms along the surface before
      being trapped into the potential well located over the hollow site.

PMID- 15974761
TI  - Cluster expansion of electronic excitations: application to fcc Ni-Al alloys.
AB  - The cluster expansion method is applied to electronic excitations and a set of
      effective cluster densities of states (ECDOS) is defined, analogous to effective
      cluster interactions (ECIs). The ECDOSs are used to generate alloy thermodynamic
      properties as well as the equation of state (EOS) of electronic excitations for
      the fcc Ni-Al systems. When parent clusters have a small size, the convergence of
      the expansion is not so good but the electronic density of state (DOS) is well
      reproduced. However, the integrals of the DOS such as the cluster expanded free
      energy, entropy, and internal energy associated with electronic excitations are
      well described at the level of the tetrahedron-octahedron cluster approximation,
      indicating that the ECDOS is applicable to produce electronic ECIs for cluster
      variation method (CVM) or Monte Carlo calculations. On the other hand, the
      Gruneisen parameter, calculated with first-principles methods, is no longer a
      constant and implies that the whole DOS profile should be considered for EOS of
      electronic excitations, where ECDOS adapts very well for disordered alloys and
      solid solutions.

PMID- 15974762
TI  - Manipulating the electronic structures of silicon carbide nanotubes by selected
      hydrogenation.
AB  - We show that the electronic and atomic structures of silicon carbide nanotubes
      (SiCNTs) undergo dramatic changes with hydrogenation from first-principles
      calculations based on density-functional theory. The exo-hydrogenation of a
      single C atom results in acceptor states close to the highest occupied valence
      band of pristine SiCNT, whereas donor states close to the lowest unoccupied
      conduction band appear as a Si atom being hydrogenated. Upon fully hydrogenating
      Si atoms, (8,0) and (6,6) SiCNTs become metallic with very high density of states
      at the Fermi level. The full hydrogenation of C atoms, on the other hand,
      increases the band gap to 2.6 eV for (8,0) SiCNT and decreases the band gap to
      1.47 eV for (6,6) SiCNT, respectively. The band gap of SiCNTs can also be greatly
      increased through the hydrogenation of all the atoms.

PMID- 15974763
TI  - Effect of platinum on the photophysical properties of a series of phenyl-ethynyl
      oligomers.
AB  - In this work we detail the photophysical properties of a series of butadiynes
      having the formula H-(C6H4-C[triple bond]C)n-(C[triple bond]C-C6H4)n-H, n=1-3 and
      ligands H-(C6H4-C[triple bond]C)n-H, n=1-3 and compare these to previous work
      done on a complimentary series of platinum-containing complexes having the
      formula trans-Pt[(PC4H9)3]2[(C[triple bond]-C6H4)n-H]2, n=1-3. We are interested
      in understanding the role of the platinum in the photophysical properties. We
      found that there is conjugation through the platinum in the singlet states, but
      the triplet states show more complex behavior. The T1 exciton, having metal-to
      ligand charge-transfer character, is most likely confined to one ligand but the
      Tn exciton appears to have ligand-to-metal charge-transfer character. The
      platinum effect was largest when n=1. When n=2-3, the S0-S1,S1-S0,T1-S0, and T1
      Tn spectral properties of the platinum complex are less influenced by the metal,
      becoming equivalent to those of the corresponding butadiynes. When n=1, platinum
      decreases the triplet state lifetime, but its effect diminishes as n increases to
      2.

PMID- 15974764
TI  - Six-dimensional quantum dynamics of (v=0,j=0)D2 and of (v=1,j=0)H2 scattering
      from Cu111.
AB  - We report six-dimensional quantum dynamics calculations of the dissociative
      scattering of molecular hydrogen from the copper111 surface. Two potential energy
      surfaces are investigated and the results are compared with experiment. Our study
      completes the preliminary work of Somers et al. [Chem. Phys. Lett. 360, 390
      (2002)] and focuses on the role of initial vibrational excitation and on isotopic
      effects. None of the two investigated potential energy surfaces is found
      satisfactory: the use of neither potential yields reaction and vibrational
      excitation probabilities and vibrational efficacies that are in close agreement
      with experiment. In addition to showing the shortcomings of existing potential
      energy surfaces we point out an inconsistency in the experimental fits for D2.

PMID- 15974765
TI  - Interaction between zigzag single-wall carbon nanotubes and polymers: a density
      functional study.
AB  - Density-functional all-electrons calculations within local-density approximation
      show that the two isoelectronic polymers poly(para-phenylene) and poly(para
      borazylene) weakly interact with zigzag single-walled carbon nanotubes. The
      analysis of the electronic properties of the joint systems, both with the polymer
      inside and outside the nanotubes, reveals a physisorption process with small
      changes in band structures and densities of states with respect to the
      constituents. We evaluate the potential barrier arising between polymers and
      nanotubes. Finally, we remark a generic selectivity of poly(para-phenylene) with
      respect to the electronic behavior of nanotubes, leading to a change in the
      density of states of metallic tubules.

PMID- 15974766
TI  - A molecular model for cohesive slip at polymer melt/solid interfaces.
AB  - A molecular model is proposed which predicts wall slip by disentanglement of
      polymer chains adsorbed on a wall from those in the polymer bulk. The dynamics of
      the near-wall boundary layer is found to be governed by a nonlinear equation of
      motion, which accounts for such mechanisms on surface chains as convection,
      retraction, constraint release, and thermal fluctuations. This equation is valid
      over a wide range of grafting regimes, including those in which interactions
      between neighboring adsorbed molecules become essential. It is not closed since
      the dynamics of adsorbed chains is shown to be coupled to that of polymer chains
      in the bulk via constraint release. The constitutive equations for the layer and
      bulk, together with continuity of stress and velocity, are found to form a closed
      system of equations which governs the dynamics of the whole "bulk+boundary layer"
      ensemble. Its solution provides a stick-slip law in terms of the molecular
      parameters and extruder geometry. The model is quantitative and contains only
      those parameters that can be measured directly, or extracted from independent
      rheological measurements. The model predictions show a good agreement with
      available experimental data.

PMID- 15974767
TI  - Classical trajectory study of collisions of Ar with alkanethiolate self-assembled
      monolayers: potential-energy surface effects on dynamics.
AB  - We have investigated collisions between Ar and alkanethiolate self-assembled
      monolayers (SAMs) using classical trajectory calculations with several potential
      energy surfaces. The legitimacy of the potential-energy surfaces is established
      through comparison with molecular-beam data and ab initio calculations. Potential
      energy surfaces used in previous work overestimate the binding of Ar to the SAM,
      leading to larger energy transfer than found in the experiments. New
      calculations, based on empirical force fields that better reproduce ab initio
      calculations, exhibit improved agreement with the experiments. In particular,
      polar-angle-dependent average energies calculated with explicit-atom potential
      energy surfaces are in excellent agreement with the experiments. Polar- and
      azimuthal-angle-dependent product translational energies are examined to gain
      deeper insight into the dynamics of Ar+SAM collisions.

PMID- 15974768
TI  - Atomistic simulation of nanoporous layered double hydroxide materials and their
      properties. I. Structural modeling.
AB  - An atomistic model of layered double hydroxides, an important class of nanoporous
      materials, is presented. These materials have wide applications, ranging from
      adsorbents for gases and liquid ions to nanoporous membranes and catalysts. They
      consist of two types of metallic cations that are accommodated by a close-packed
      configuration of OH- and other anions in a positively charged brucitelike layer.
      Water and various anions are distributed in the interlayer space for charge
      compensation. A modified form of the consistent-valence force field, together
      with energy minimization and molecular dynamics simulations, is utilized for
      developing an atomistic model of the materials. To test the accuracy of the
      model, we compare the vibrational frequencies, x-ray diffraction patterns, and
      the basal spacing of the material, computed using the atomistic model, with our
      experimental data over a wide range of temperature. Good agreement is found
      between the computed and measured quantities.

PMID- 15974769
TI  - Theoretical analysis of growth of ZnO nanorods on the amorphous surfaces.
AB  - Semiconductor nanorod arrays on a substrate have a preferential alignment
      orientation that minimizes the excessive free energy of the system. In the case
      of wet chemically synthesized zinc oxide (ZnO) nanorod on the amorphous surfaces,
      the thermodynamic driving force determines the orientation to be normal to the
      surface. Among the various kinds of amorphous surfaces, the spherical seed layer
      composed of ZnO precursors gives isotropic radially aligned arrays. For other
      surfaces, such as wrinkled and planar ZnO precursor thin film, nanorod arrays are
      aligned to be perpendicular to the tangential line of the surface. The maximum
      value of the aspect ratio of the nanorod is determined by the thermodynamic
      relationship. The number density of nanorods per unit precursor particles
      decreases with increasing contact angle of the seed particles.

PMID- 15974770
TI  - Kinetics of protein binding in solid-phase immunoassays: theory.
AB  - In a solid-phase immunoassay, binding between an antigen and its specific
      antibody takes place at the boundary of a liquid and a solid phase. One of the
      reactants (receptor) is immobilized on a surface. The other reactant (ligand) is
      initially free in solution. We present a theory describing the kinetics of
      immunochemical reaction in such a system. A single essential restriction of the
      theory is the assumption that the reaction conditions are uniform along the
      binding surface. In general, the reaction rate as a function of time can be
      obtained numerically as a solution of a nonlinear integral equation. For some
      special cases, analytical solutions are available. Various immunoassay geometries
      are considered, in particular, the case when the reaction is carried out on a
      microspot.

PMID- 15974771
TI  - Towards SiC surface functionalization: an ab initio study.
AB  - We present a microscopic model of the interaction and adsorption mechanism of
      simple organic molecules on SiC surfaces as obtained from ab initio molecular
      dynamics simulations. Our results open the way to functionalization of silicon
      carbide, a leading candidate material for biocompatible devices.

PMID- 15974772
TI  - Molecular dynamics study of thermal phenomena in an ultrathin liquid film sheared
      between solid surfaces: the influence of the crystal plane on energy and momentum
      transfer at solid-liquid interfaces.
AB  - A molecular dynamics study has been performed on a liquid film sheared between
      moving solid walls. Thermal phenomena that occur in the Couette-like flow were
      examined, including energy conversion from macroscopic flow energy to thermal
      energy, i.e., viscous heating in the macroscopic sense, and heat conduction from
      the liquid film to the solid wall via liquid-solid interfaces. Four types of
      crystal planes of fcc lattice were assumed for the surface of the solid wall. The
      jumps in velocity and temperature at the interface resulting from deteriorated
      transfer characteristics of thermal energy and momentum at the interface were
      observed. It was found that the transfer characteristics of thermal energy and
      momentum at the interfaces are greatly influenced by the types of crystal plane
      of the solid wall surface which contacts the liquid film. The mechanism by which
      such a molecular scale structure influences the energy transfer at the interface
      was examined by analyzing the molecular motion and its contribution to energy
      transfer at the solid-liquid interface.

PMID- 15974773
TI  - Surface reorganization accompanying the formation of sulfite and sulfate by
      reaction of sulfur dioxide with oxygen on Ag111.
AB  - On the Ag(111)-p(4x4)-O surface SO2(g) reacts with oxygen according to
      SO2(g)+O(a)-->SO3(a). Sulfite forms in a (2 radical3x2 radical3)R30 degrees
      structure. The restructuring of the surface atoms during sulfite formation is
      indicative of the deconstruction of the p(4x4)-O structure. Heating the sulfite
      covered surface to 700 K affects the disproportionation of SO3 to SO4 in a (4
      square root of 3 x square root of 3)R30 degrees structure accompanied by the
      desorption of SO2(g) and smoothing of the surface. Continued heating beyond 700 K
      affects the complete decomposition of sulfate to SO2(g) and O2(g).

PMID- 15974775
TI  - Measurement of rock-core capillary pressure curves using a single-speed
      centrifuge and one-dimensional magnetic-resonance imaging.
AB  - Capillary pressure curves are widely used in materials, soil, and environmental
      sciences, and especially in the petroleum industry. The traditional (Hassler
      Brunner) interpretation of centrifugal capillary pressure data is based on
      several assumptions. These assumptions are known to lead to significant errors in
      the measurement of capillary pressure curves. In this work, we propose a new
      "single-shot" method to measure the capillary pressure curve of a long
      sedimentary rock core using a single-speed centrifuge experiment and magnetic
      resonance imaging to directly determine the water saturation distribution along
      the length of the sample. Since only a single moderate centrifuge speed is
      employed, the effect of gravity can be ignored and the outlet boundary condition
      of the core plug was maintained. The capillary pressure curve obtained by the
      single-shot method is remarkably consistent with results determined with
      conventional mercury-intrusion methods. The proposed method is much faster and
      more precise than traditional centrifuge methods.

PMID- 15974774
TI  - Exciton dissociation dynamics in model donor-acceptor polymer heterojunctions. I.
      Energetics and spectra.
AB  - In this paper we consider the essential electronic excited states in parallel
      chains of semiconducting polymers that are currently being explored for
      photovoltaic and light-emitting diode applications. In particular, we focus upon
      various type II donor-acceptor heterojunctions and explore the relation between
      the exciton binding energy to the band offset in determining the device
      characteristic of a particular type II heterojunction material. As a general
      rule, when the exciton binding energy is greater than the band offset at the
      heterojunction, the exciton will remain the lowest-energy excited state and the
      junction will make an efficient light-emitting diode. On the other hand, if the
      offset is greater than the exciton binding energy, either the electron or hole
      can be transferred from one chain to the other. Here we use a two-band exciton to
      predict the vibronic absorption and emission spectra of model polymer
      heterojunctions. Our results underscore the role of vibrational relaxation and
      suggest that intersystem crossings may play some part in the formation of charge
      transfer states following photoexcitation in certain cases.

PMID- 15974776
TI  - Pretransitional behavior of a water in liquid crystal microemulsion close to the
      demixing transition: evidence for intermicellar attraction mediated by
      paranematic fluctuations.
AB  - We present a study of a water-in-oil microemulsion in which surfactant coated
      water nanodroplets are dispersed in the isotropic phase of the thermotropic
      liquid-crystal penthyl-cyanobiphenyl (5CB). As the temperature is lowered below
      the isotropic to nematic phase transition of pure 5CB, the system displays a
      demixing transition leading to a coexistence of a droplet-rich isotropic phase
      with a droplet-poor nematic. The transition is anticipated, in the high T side,
      by increasing pretransitional fluctuations in 5CB molecular orientation and in
      the nanodroplet concentration. The observed phase behavior supports the notion
      that the nanosized droplets, while large enough for their statistical behavior to
      be probed via light scattering, are also small enough to act as impurities,
      disturbing the local orientational ordering of the liquid crystal and thus
      experiencing pretransitional attractive interaction mediated by paranematic
      fluctuations. The pretransitional behavior, together with the topology of the
      phase diagram, can be understood on the basis of a diluted Lebwohl-Lasher model
      which describes the nanodroplets simply as holes in the liquid crystal.

PMID- 15974777
TI  - Melting of icosahedral gold nanoclusters from molecular dynamics simulations.
AB  - Molecular dynamics simulations show that gold clusters with about 600-3000 atoms
      crystallize into a Mackay icosahedron upon cooling from the liquid. A detailed
      surface analysis shows that the facets on the surface of the Mackay icosahedral
      gold clusters soften but do not premelt below the bulk melting temperature. This
      softening is found to be due to the increasing mobility of vertex and edge atoms
      with temperature, which leads to inter-layer and intra-layer diffusion, and a
      shrinkage of the average facet size, so that the average shape of the cluster is
      nearly spherical at melting.

PMID- 15974778
TI  - Electronic structure of a vapor-deposited metal-free phthalocyanine thin film.
AB  - The electronic structure of a vapor-sublimated thin film of metal-free
      phthalocyanine (H2Pc) is studied experimentally and theoretically. An atom
      specific picture of the occupied and unoccupied electronic states is obtained
      using x-ray-absorption spectroscopy (XAS), core- and valence-level x-ray
      photoelectron spectroscopy (XPS), and density-functional theory (DFT)
      calculations. The DFT calculations allow for an identification of the
      contributions from individual nitrogen atoms to the experimental N1s XAS and
      valence XPS spectra. This comprehensive study of metal-free phthalocyanine is
      relevant for the application of such molecules in molecular electronics and
      provides a solid foundation for identifying modifications in the electronic
      structure induced by various substituent groups.

PMID- 15974779
TI  - Ab initio computational investigation of physisorption of molecular hydrogen on
      achiral single-walled carbon nanotubes.
AB  - Using relatively approximated methods, physisorption of molecular hydrogen on
      single-walled carbon nanotubes (SWCNTs) as a mechanism to develop hydrogen
      storage systems has been only partially investigated in literature. Here, we use
      ab initio molecular-orbital theory, at benchmark quality level, to provide a more
      complete description about the mentioned mechanism. Physisorption inside and
      outside achiral-armchair and zigzag-SWCNTs, in the range of diameters from about
      6 A-chiral vectors (5,5) and (8,0)-to more than 30 A-chiral vectors (30,30) and
      (40,0)-was examined. Perpendicular, longitudinal, and transversal configurations,
      with the hydrogen molecule centered on an aromatic ring, were taken into account.
      SWCNTs were modeled as curved coronenelike (C24H12) graphene sheets. Local
      modeling strategies, using more complete basis sets for the adsorbate and for the
      nearest atoms to the adsorbate than for the lion's share of the substrate, at the
      Moller-Plesset second-order correlation level, were selected for numerical
      treatment. Basis-set superposition errors were corrected by means of the
      counterpoise method of Bois and Bernardi. It was found that physisorption of
      molecular hydrogen on SWCNTs would depend mainly on the diameter being virtually
      independent of the chirality. Lowest physisorption energies, up to 20% less than
      that on planar graphene, would be reached outside nanotubes in the range of
      diameters of 6-10 A. For hydrogen storage purposes, highest physisorption
      energies, up to 40% greater than that on planar graphene, but not more, would be
      reached inside nanotubes in the relatively narrow range of diameters of 10-20 A.
      Finally, for diameters from 20 A onwards physisorption of molecular hydrogen on
      SWCNTs would be in the range of +/-10% of that on planar graphene. To our
      knowledge, this would be the most complete and realistic theoretical
      investigation of the target physisorption mechanism to date.

PMID- 15974780
TI  - Multifractal analysis of dynamic potential surface of ion-conducting materials.
AB  - A multifractal analysis using singularity spectra [T.C. Halsey et al., Phys. Rev.
      A 33, 1141 (1986)] provides a general tool to study the temporal-spatial
      properties of particles in complex disordered materials such as ions in ionically
      conducting glasses and melts. Obtained by molecular-dynamics simulations, the
      accumulated positions of the particles dynamically form a structural pattern
      called the dynamical potential surface. In this work, the complex dynamical
      potential surfaces of Li ions in the lithium silicates were visualized and
      characterized by the multifractal analysis. The fractal dimensions and strength
      of the singularity related to the spatial intermittency of the dynamics are
      examined, and the relationship between dynamics and the singularity spectra is
      discussed.

PMID- 15974781
TI  - Enhancement of Raman scattering for an atom or molecule near a metal
      nanocylinder: quantum theory of spontaneous emission and coupling to surface
      plasmon modes.
AB  - An analytic expression for the electromagnetic enhancement of the spontaneous
      emission rate and Raman scattering cross-section for an excited atom or molecule
      in close proximity to a metal nanocylinder has been derived by quantum theory.
      Coupling of the atomic or molecular optical radiation into the TM0 surface
      plasmon mode of the nanocylinder results in reradiation by the cylinder, a
      process that is most efficient when the incident radiation is linearly polarized,
      with the electric field oriented parallel to the axis of the nanocylinder. For a
      silver cylinder having a radius and length of 5 and 20 nm, respectively, the
      enhancement in the spontaneous emission rate is >10(7) for variant Planck's over
      2pi omega0 approximately 2.4 eV (lambda=514 nm), which corresponds to an increase
      of approximately 10(14) in the Raman scattering cross section. This result, as
      well as the prediction that the atomic dipole generates broadband, femtosecond
      pulses, are in qualitative agreement with previously reported experiments
      involving metal nanoparticle aggregates. The theoretical results described here
      are expected to be of value in guiding future nonlinear optical experiments in
      which carbon nanotubes or metal nanowires with controllable physical and
      electrical characteristics are patterned onto a substrate and coupled with
      emitting atoms or molecules.

PMID- 15974782
TI  - The liquidlike ordering of lipid A-diphosphate colloidal crystals: the influence
      of Ca2+, Mg2+, Na+, and K+ on the ordering of colloidal suspensions of lipid A
      diphosphate in aqueous solutions.
AB  - A comprehensive study was performed on electrostatically stabilized aqueous
      dispersion of lipid A-diphosphate in the presence of bound Ca2+, Mg2+, K+, and
      Na+ ions at low ionic strength (0.10-10.0-mM NaCl, 25 degrees C) over a range of
      volume fraction of 1.0 x 10(-4)< or =phi< or =4.95 x 10(-4). These suspensions
      were characterized by light scattering (LS), quasielastic light scattering, small
      angle x-ray scattering, transmission electron microscopy, scanning electron
      microscopy, conductivity measurements, and acid-base titrations. LS and electron
      microscopy yielded similar values for particle sizes, particle size
      distributions, and polydispersity. The measured static structure factor, S(Q), of
      lipid A-diphosphate was seen to be heavily dependent on the nature and
      concentration of the counterions, e.g., Ca2+ at 5.0 nM, Mg2+ at 15.0 microM, and
      K+ at 100.0 microM (25 degrees C). The magnitude and position of the S(Q) peaks
      depend not only on the divalent ion concentration (Ca2+ and Mg2+) but also on the
      order of addition of the counterions to the lipid A-diphosphate suspension in the
      presence of 0.1-microM NaCl. Significant changes in the rms radii of gyration
      (R2G) 1/2 of the lipid A-diphosphate particles were observed in the presence of
      Ca2+ (24.8+/-0.8 nm), Mg2+ (28.5+/-0.7 nm), and K+ (25.2+/-0.6 nm), whereas the
      Na+ salt (29.1+/-0.8 nm) has a value similar to the one found for the de-ionized
      lipid A-diphosphate suspensions (29.2+/-0.8 nm). Effective particle charges were
      determined by fits of the integral equation calculations of the polydisperse
      static structure factor, S(Q), to the light-scattering data and they were found
      to be in the range of Z*=700-750 for the lipid A-diphosphate salts under
      investigation. The light-scattering data indicated that only a small fraction of
      the ionizable surface sites (phosphate) of the lipid A-diphosphate was partly
      dissociated (approximately 30%). It was also discovered that a given amount of
      Ca2+ (1.0-5.0 nM) or K+ (100 microM) influenced the structure much more than Na+
      (0.1-10.0-mM NaCl) or Mg2+ (50 microM). By comparing the heights and positions of
      the structure factor peaks S(Q) for lipid A-diphosphate-Na+ and lipid A
      diphosphate-Ca2+, it was concluded that the structure factor does not depend
      simply on ionic strength but more importantly on the internal structural
      arrangements of the lipid A-diphosphate assembly in the presence of the bound
      cations. The liquidlike interactions revealed a considerable degree of ordering
      in solution accounting for the primary S(Q) peak and also the secondary minimum
      at large particle separation. The ordering of lipid A-diphosphate-Ca2+ colloidal
      crystals in suspension showed six to seven discrete diffraction peaks and
      revealed a face-centered-cubic (fcc) lattice type (a=56.3 nm) at a volume
      fraction of 3.2 x 10(-4)< or =phi< or =3.9 x 10(-4). The K+ salt also exhibited a
      fcc lattice (a=55.92 nm) at the same volume fractions, but reveals a different
      peak intensity distribution, as seen for the lipid A-diphosphate-Ca2+ salt.
      However, the Mg2+ and the Na+ salts of lipid A-diphosphate showed body-centered
      cubic (bcc) lattices with a=45.50 nm and a=41.50 nm, respectively (3.2 x 10(-4)<
      or =phi< or =3.9 x 10(-4)), displaying the same intensity distribution with the
      exception of the (220) diffraction peaks, which differ in intensity for both
      salts of lipid A-diphosphate.

PMID- 15974783
TI  - Nonequilibrium effects in diffusion of interacting particles on vicinal surfaces.
AB  - We study the influence of nonequilibrium conditions on the collective diffusion
      of interacting particles on vicinal surfaces. To this end, we perform Monte Carlo
      simulations of a lattice-gas model of an ideal stepped surface, where adatoms
      have nearest-neighbor attractive or repulsive interactions. Applying the
      Boltzmann-Matano method to spreading density profiles of the adatoms allows the
      definition of an effective, time-dependent collective diffusion coefficient D(C)
      (t)(theta) for all coverages theta. In the case of diffusion across the steps and
      strong binding at lower step edges we observe three stages in the behavior of the
      corresponding D(xx,C) (t)(theta). At early times when the adatoms have not yet
      crossed the steps, D(xx,C) (t)(theta) is influenced by the presence of steps only
      weakly. At intermediate times, where the adatoms have crossed several steps,
      there are sharp peaks at coverages theta<1L and theta>1-1L, where L is the
      terrace width. These peaks are due to different rates of relaxation of the
      density at successive terraces. At late stages of spreading, these peaks vanish
      and D(xx,C) (t)(theta) crosses over to its equilibrium value, where for strong
      step edge binding there is a maximum at theta=1L. In the case of diffusion in
      direction along the steps the nonequilibrium effects in D(yy,C) (t)(theta) are
      much weaker, and are apparent only when diffusion along ledges is strongly
      suppressed or enhanced.

PMID- 15974784
TI  - Permeation and gating in proteins: kinetic Monte Carlo reaction path following.
AB  - We present a new Monte Carlo technique, kinetic Monte Carlo reaction path
      following (kMCRPF), for the computer simulation of permeation and large-scale
      gating transitions in protein channels. It combines ideas from Metropolis Monte
      Carlo (MMC) and kinetic Monte Carlo (kMC) algorithms, and is particularly
      suitable when a reaction coordinate is well defined. Evolution of transition
      proceeds on the reaction coordinate by small jumps (kMC technique) toward the
      nearest lowest-energy uphill or downhill states, with the jumps thermally
      activated (constrained MMC). This approach permits navigation among potential
      minima on an energy surface, finding the minimum-energy paths and determining
      their associated free-energy profiles. The methodological and algorithmic
      strategies underlying the kMCRPF method are described. We have tested it using an
      analytical model and applied it to study permeation through the curvilinear ClC
      chloride and aquaporin pores and to gating in the gramicidin A channel. These
      studies of permeation and gating in real proteins provide extensive procedural
      tests of the method.

PMID- 15974785
TI  - Polymer distribution in connected spherical domains.
AB  - The distribution of neutral and charged polymers with different flexibilities
      between two spheres of varying volume connected by a short and narrow cylinder
      has been investigated by Monte Carlo simulations. The uncharged chain displayed
      mostly a single-sphere occupancy due to the high conformational entropy penalty
      of crossing the cylindrical domain, whereas for the charged polymer a double
      sphere occupancy was obtained, except for very different spherical volumes. The
      origin of this different occupancy behavior stems from the counterion entropy. At
      increasing stiffness, a stronger preference for double-sphere occupancy was
      predicted.

PMID- 15974786
TI  - Does coarsening begin during the initial stages of spinodal decomposition?
AB  - The initial stages of spinodal decomposition were studied by subjecting a
      critical blend of model polyolefins to a pressure quench and monitoring the
      evolution by time-resolved small angle neutron scattering. Contrary to the
      predictions of the widely accepted Cahn-Hilliard-Cook theory, we demonstrate that
      coarsening of the phase-separated structure begins immediately after the quench
      and occurs throughout the initial stages of spinodal decomposition.

PMID- 15974787
TI  - Surface and bulk dissolution properties, and selectivity of DNA-linked
      nanoparticle assemblies.
AB  - Using a simple mean-field model, we analyze the surface and bulk dissolution
      properties of DNA-linked nanoparticle assemblies. We find that the dissolution
      temperature and the sharpness of the dissolution profiles increase with the
      grafting density of the single-stranded DNA "probes" on the surface of colloids.
      The surface grafting density is controlled by the linker occupation number, in
      analogy with quantum particles obeying fractional statistics. The dissolution
      temperature increases logarithmically with the salt concentration. This is in
      agreement with the experimental findings [R. Jin, G. Wu, Z. Li, C. A. Mirkin, and
      G. C. Schatz, J. Am. Chem. Soc. 125, 1643 (2003)]. By exploiting the unique phase
      behavior of DNA-coated colloids, it should be possible to detect multiple
      "targets" in a single experiment by essentially mapping the DNA base-pair
      sequence onto the phase behavior of DNA-linked nanoparticle solution.

PMID- 15974788
TI  - Sedimentation of spheres at small Reynolds number.
AB  - The effect of fluid inertia on the settling of spheres in a viscous
      incompressible fluid is studied in the limit of small Reynolds number. The
      kinetic energy of flow depends on the positions of the spheres, and gives rise to
      forces on the spheres. In the dilute limit it suffices to study the corresponding
      pair interaction. The interaction is calculated from the Stokes flow for two
      spheres settling between plane walls in the point particle limit. The dissipative
      interaction between a pair of spheres is calculated from the Proudman-Pearson [I.
      Proudman and J. R. A. Pearson, J. Fluid Mech. 2, 237 (1957)] solution of the
      Navier-Stokes equations for flow about a sphere in unbounded geometry. The
      combination of kinetic and dissipative interaction gives rise to a repulsive
      force of range of the order of the sphere diameter divided by the Reynolds
      number.

PMID- 15974789
TI  - Kinetic pathway to double-gyroid structure.
AB  - We have investigated the structural development during order-order transitions to
      the double-gyroid (DG) phase of nonionic surfactant/water systems based on two
      dimensional small-angle x-ray scattering patterns from highly oriented ordered
      mesophases. The lamellar (L) to DG transition proceeds through two intermediate
      structures, a fluctuating perforated layer structure having ABAB stacking and a
      hexagonal perforated lamellar structure with ABCABC stacking (HPLABC). For a
      hexagonally packed cylinder (H) to DG transition, we also observed the HPLABC
      structure as the intermediate phase, thus the HPLABC is an entrance structure for
      the DG phase. The hexagonal perforated lamellar (HPL) structure consists of
      hexagonally packed holes surrounded by the planar tripods, and the transition
      from HPL structure to the DG phase proceeds by rotation of the dihedral angle of
      connected tripods. A geometrical consideration shows that large deformations of
      HPL planes are necessary to form the DG structure from the HPLABC structure,
      whereas the transition from a HPL structure with ABAB stacking (HPLAB) to the DG
      structure is straightforward. In spite of the topological constraints, the HPLABC
      structure is observed in the kinetic pathway to the DG structure.

PMID- 15974790
TI  - Mechanism of enhanced positronium formation in low-temperature polymers.
AB  - An enhanced positronium (Ps) formation in low-temperature polymers has been
      widely observed. The additional positronium formation is due to shallow trapped
      electrons in them. Positron annihilation lifetime spectroscopy was applied to
      investigate the Ps formation in a series of polymers, such as low-density
      polyethylene, ethylene-methyl methacrylate copolymers with various methyl
      methacrylate contents, and pure poly(methyl methacrylate) at low temperature. An
      analysis of the experimental data based on simple kinetic equations enables one
      to understand the Ps formation mechanism in polymers during low-temperature
      positron annihilation experiments as functions of the temperature and elapsed
      time. Good fittings of the experimental data were obtained. The fitting
      parameters seemed to show clear physical meanings.

PMID- 15974791
TI  - Morphological structures formed by grafted polymers in poor solvents.
AB  - We study a system of grafted polymers in a poor solvent by self-consistent-field
      methods as well as Monte-Carlo simulation methods. We observe a number of
      different morphological structures including an inverted solvent micelle or hole
      in the polymer layer, a lamella-like micelle structure, and fused, spherical
      micelle structures. These structures can be obtained by either varying the
      grafting density or chain length. We also develop a scaling theory for the
      existence of these structures and find reasonable agreement between this theory
      and our numerical calculations.

PMID- 15974792
TI  - Cyclization of Rouse chains at long- and short-time scales.
AB  - We have investigated cyclization of a Rouse chain at long and short times by a
      Langevin dynamics simulation method. We measure St, the fraction of nonreacted
      chains, for polymerizations ranging from Z=5 to Z=800 and capture distances
      ranging from a=0.1b to a=8b where b is the bond length. Comparison is made with
      two theoretical approaches. The first is a decoupling approximation used by
      Wilemski and Fixman to close the relevant master equation [J. Chem. Phys. 58,
      4009 (1973); 60, 866 (1974)]. The second approach is the renormalization group
      arguments of Friedman and O'Shaughnessy [Phys. Rev. Lett 60, 64 (1988); J. Phys.
      II 1, 471 (1991)]. We find that at long times St decays as a single exponential
      with rate k(infinity). The scaled decay rate K=k(infinity)tauR appears to
      approach a constant value independent of the capture distance for very large
      chains consistent with the predictions of both the renormalization group (RG) and
      Wilemski-Fixman closure approximation. We extract K*, the long chain limit of K,
      from the fixed point a=a* where K is independent of Z. K* is larger than both the
      RG and closure predictions but much closer to the RG result. More convincing
      evidence for the RG analysis is obtained by comparing the short-time decay of St
      to long-time results. The RG analysis predicts that dSdt should decay as a power
      law at early times and that the exponent in the power law is related to K by a
      simple expression with no free parameters. Our simulations find remarkable
      agreement with this parameter-free prediction even for relatively short chains.
      We discuss possible experimental consequences of our result.

PMID- 15974793
TI  - Effect of attractive interactions on the structure of polymer melts confined
      between surfaces: a density-functional approach.
AB  - A density-functional theory is presented to study the structure of polymers,
      having attractive interactions, confined between attractive surfaces. The theory
      treats the ideal-gas free-energy functional exactly and uses weighted density
      approximation for the hard-chain contribution to the excess free-energy
      functional. The bulk interactions of freely jointed hard spheres are obtained
      from generalized Flory equation of state and the attractive interactions are
      calculated using the direct correlation function obtained from the polymer
      reference interaction site model theory along with the mean spherical
      approximation closure. The theoretical predictions are found to be in quite good
      agreement with the Monte Carlo simulation results for varying densities, chain
      lengths, and different interaction potentials. The results confirm important
      implications of using different approximations for the hard-sphere and attractive
      interactions.

PMID- 15974794
TI  - Nematic-nematic demixing in polydisperse thermotropic liquid crystals.
AB  - We consider the effects of polydispersity on isotropic-nematic phase equilibria
      in thermotropic liquid crystals, using a Maier-Saupe theory [Z. Naturforsch. A
      13A, 564 (1958)] with factorized interactions. A sufficient spread (approximately
      50%) in the interaction strengths of the particles leads to phase separation into
      two or more nematic phases, which can in addition coexist with an isotropic
      phase. The isotropic-nematic coexistence region widens dramatically as
      polydispersity is increased, leading to reentrant isotropic-nematic phase
      separation in some regions of the phase diagram. We show that similar phenomena
      will occur also for nonfactorized interactions as long as the interaction
      strength between any two particle species is lower than the mean of the
      intraspecies interactions.

PMID- 15974795
TI  - Diffusion exchange NMR spectroscopic study of dextran exchange through
      polyelectrolyte multilayer capsules.
AB  - Diffusion exchange of dextran with molecular weights 4.4 and 77 kDa through
      polyelectrolyte multilayer (PEM) hollow capsules consisting of four bilayers of
      polystyrene sulfonate/polydiallyldimethylammonium chloride has been investigated
      using two-dimensional nuclear-magnetic-resonance methods: diffusion-diffusion
      exchange spectroscopy (DEXSY) and diffusion-relaxation correlation spectroscopy
      (DRCOSY). Results obtained in DRCOSY experiments show that the diffusion process
      of dextran 77 kDa exhibits an observation time dependence suggesting a diffusion
      behavior restricted by confinement. We find evidence for both single capsule and
      capsule aggregate states, with a partitioning of the 77-kDa dextran between the
      free and capsule states much larger than that suggested by volume fraction alone.
      Results from DEXSY experiments show that dextran 77 kDa is in diffusive exchange
      through the capsules with an exchange time of around 1 s. In contrast, the
      capsules have no detectable influence on the diffusion process of the dextran 4.4
      kDa. This quantitative information may be used in designing PEM capsules as drug
      carriers.

PMID- 15974796
TI  - The molecular structure and orientation of antiferroelectric liquid crystal using
      the density-functional theory and two-dimensional correlation-polarized infrared
      spectroscopy.
AB  - The structure and vibrational frequencies of the chiral antiferroelectric liquid
      crystal molecule, 4-(1-methyheptyloxycarbonyl) phenyl-4-(4'-octyloxy) benzoate
      (MHOCPOOB), have been calculated using the density-functional theory (DFT) with
      the Becke-3 Lee-Yang-Parr/6-31G(d,p) level. The observed vibrational spectra have
      been resolved and assigned in detail by comparison to the computed values. The
      results indicate that the computed and observed spectra are in good agreement
      with each other. The stable molecular structure obtained with the DFT theory
      shows that the two hydrocarbon chains are all-trans zigzag conformer and nearly
      perpendicular to each other. The orientation of the mesogen part and the
      hydrocarbon chains for MHOCPOOB in the Sm-C*A phase are investigated by employing
      the polarization-angle-dependent infrared spectra in the electric-field induced
      and the two-dimensional correlation spectroscopy. After combining the
      experimental and theoretical results, it can be concluded that the azimuth of the
      achiral and chiral chains is opposite to each other, the orientation of the
      achiral chain is almost the same direction as the mesogen core, and the
      orientation of the chiral chain is nearly perpendicular to the mesogen part. The
      achiral and chiral CH2 chains are both a probable all-trans zigzag conformer.

PMID- 15974797
TI  - A model for nonexponential relaxation and aging in dissipative systems.
AB  - The nonexponential relaxation and aging inherent to complex dynamics manifested
      in a wide variety of dissipative systems are analyzed through a model of
      diffusion in phase space in the presence of a nonconservative force. The action
      of this force establishes a heat flow which maintains the system away from
      equilibrium. The inability of the system to find its equilibrium state becomes
      apparent through the presence of an effective temperature field. This is the
      temperature of the stationary nonequilibrium state reached by the system
      satisfying a generalized version of the fluctuation-dissipation theorem. The
      presence of a nonequilibrium temperature leads to a hierarchy of relaxation times
      responsible for the aging phenomena and to a relation similar to the Vogel
      Fulcher-Tammann law [H. Vogel, Phys. Z. 22, 645 (1921); G. S. Fulcher, J. Am.
      Ceram. Soc. 8, 339 (1925); 8, 789 (1925); G. Tammann and W. Hesse, Z. Anorg.
      Allg. Chem. 156, 245 (1926)].

PMID- 15974798
TI  - A minimal proteinlike lattice model: an alpha-helix motif.
AB  - A simple protein model of a four-helix bundle motif on a face-centered cubic
      lattice has been studied. Total energy of a conformation includes attractive
      interactions between hydrophobic residues, repulsive interactions between
      hydrophobic and polar residues, and a potential that favors helical turns. Using
      replica exchange Monte Carlo simulations we have estimated a set of parameters
      for which the native structure is a global minimum of conformational energy. Then
      we have shown that all the above types of interactions are necessary to guarantee
      the cooperativity of folding transition and to satisfy the thermodynamic
      hypothesis.

PMID- 15974799
TI  - Two-particle friction in a mesoscopic solvent.
AB  - The effects of hydrodynamic interactions on the friction tensors for two
      particles in solution are studied. The particles have linear dimensions on
      nanometer scales and are either simple spherical particles interacting with the
      solvent through repulsive Lennard-Jones forces or are composite cluster particles
      whose atomic components interact with the solvent through repulsive Lennard-Jones
      forces. The solvent dynamics is modeled at a mesoscopic level through
      multiparticle collisions that conserve mass, momentum, and energy. The dependence
      of the two-particle relative friction tensors on the interparticle separation
      indicates the importance of hydrodynamic interactions for these nanoparticles.

PMID- 15974800
TI  - Calculation of Cl2 vibrational distributions after vibrational predissociation of
      He2-Cl2.
AB  - An approximate model is tested in order to obtain the vibrational distributions
      of the Cl2 fragment produced after He2-Cl2(B) predissociation, when the dynamics
      is simulated by a full-dimensional wave-packet method. The model is intended to
      overcome the limitations imposed to a rigorous calculation of the vibrational
      distributions by the use of a finite grid size and absorbing boundary conditions.
      The good agreement found between the present results and the available
      experimental data indicates that the model is able to provide realistic estimates
      for the product vibrational distributions.

PMID- 15974803
TI  - The Ews-ERG fusion protein can initiate neoplasia from lineage-committed
      haematopoietic cells.
AB  - The EWS-ERG fusion protein is found in human sarcomas with the chromosomal
      translocation t(21;22)(q22;q12), where the translocation is considered to be an
      initiating event in sarcoma formation within uncommitted mesenchymal cells,
      probably long-lived progenitors capable of self renewal. The fusion protein may
      not therefore have an oncogenic capability beyond these progenitors. To assess
      whether EWS-ERG can be a tumour initiator in cells other than mesenchymal cells,
      we have analysed Ews-ERG fusion protein function in a cellular environment not
      typical of that found in human cancers, namely, committed lymphoid cells. We have
      used Ews-ERG invertor mice having an inverted ERG cDNA cassette flanked by loxP
      sites knocked in the Ews intron 8, crossed with mice expressing Cre recombinase
      under the control of the Rag1 gene to give conditional, lymphoid-specific
      expression of the fusion protein. Clonal T cell neoplasias arose in these mice.
      This conditional Ews gene fusion model of tumourigenesis shows that Ews-ERG can
      cause haematopoietic tumours and the precursor cells are committed cells. Thus,
      Ews-ERG can function in cells that do not have to be pluripotent progenitors or
      mesenchymal cells.

PMID- 15974804
TI  - Evolution, systematics, and phylogeography of pleistocene horses in the new
      world: a molecular perspective.
AB  - The rich fossil record of horses has made them a classic example of evolutionary
      processes. However, while the overall picture of equid evolution is well known,
      the details are surprisingly poorly understood, especially for the later Pliocene
      and Pleistocene, c. 3 million to 0.01 million years (Ma) ago, and nowhere more so
      than in the Americas. There is no consensus on the number of equid species or
      even the number of lineages that existed in these continents. Likewise, the
      origin of the endemic South American genus Hippidion is unresolved, as is the
      phylogenetic position of the "stilt-legged" horses of North America. Using
      ancient DNA sequences, we show that, in contrast to current models based on
      morphology and a recent genetic study, Hippidion was phylogenetically close to
      the caballine (true) horses, with origins considerably more recent than the
      currently accepted date of c. 10 Ma. Furthermore, we show that stilt-legged
      horses, commonly regarded as Old World migrants related to the hemionid asses of
      Asia, were in fact an endemic North American lineage. Finally, our data suggest
      that there were fewer horse species in late Pleistocene North America than have
      been named on morphological grounds. Both caballine and stilt-legged lineages may
      each have comprised a single, wide-ranging species.

PMID- 15974806
TI  - The proposal to close the armed forces institute of pathology.

PMID- 15974805
TI  - Smoking cessation and cardiovascular disease risk factors: results from the Third
      National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Cigarette smoking is a major risk factor for the development and
      progression of cardiovascular disease. While smoking is associated with increased
      levels of inflammatory markers and accelerated atherosclerosis, few studies have
      examined the impact of smoking cessation on levels of inflammatory markers. The
      degree and rate at which inflammation subsides after smoking cessation are
      uncertain. It also remains unclear as to whether traditional risk factors can
      adequately explain the observed decline in cardiovascular risk following smoking
      cessation. METHODS AND FINDINGS: Using data from 15,489 individuals who
      participated in the Third National Health and Nutrition Examination Survey
      (NHANES III), we analyzed the association between smoking and smoking cessation
      on levels of inflammatory markers and traditional cardiovascular risk factors. In
      particular, we examined changes in C-reactive protein, white blood cell count,
      albumin, and fibrinogen. Inflammatory markers demonstrated a dose-dependent and
      temporal relationship to smoking and smoking cessation. Both inflammatory and
      traditional risk factors improved with decreased intensity of smoking. With
      increased time since smoking cessation, inflammatory markers resolved more slowly
      than traditional cardiovascular risk factors. CONCLUSION: Inflammatory markers
      may be more accurate indicators of atherosclerotic disease. Inflammatory markers
      returned to baseline levels 5 y after smoking cessation, consistent with the time
      frame associated with cardiovascular risk reduction observed in both the MONICA
      and Northwick Park Heart studies. Our results suggest that the inflammatory
      component of cardiovascular disease resulting from smoking is reversible with
      reduced tobacco exposure and smoking cessation.

PMID- 15974808
TI  - Altered recognition of reparative changes in ThinPrep specimens in the College of
      American Pathologists Gynecologic Cytology Program.
AB  - CONTEXT: Previous studies have shown that the diagnosis of reparative changes in
      conventional smears in the College of American Pathologists Interlaboratory
      Comparison Program in Gynecologic Cytology is one of the least reproducible
      diagnoses. Indeed, the diagnosis of reparative changes consistently yields the
      highest false-positive rate of any negative for intraepithelial lesions and
      malignancy (NILM) cytodiagnostic category. It is unknown whether cytologists
      recognize reparative changes in ThinPrep specimens as well, or less often, as in
      conventional smears. OBJECTIVE: To assess and compare the ability of cytologists
      to recognize reparative changes in conventional and ThinPrep preparations.
      DESIGN: We compiled performance data from the College of American Pathologists
      Interlaboratory Comparison Program in Gynecologic Cytology from the 2000-2003
      program years. More than 400 slides with a reference diagnosis of reparative
      changes met our study criteria, representing a total of 11 200 individual
      responses for conventional cases and 1155 individual responses for ThinPrep
      specimens. We evaluated the results of both individual and laboratory
      participants using 2 performance criteria: the false-positive discordancy rate
      and the exact match error rate (any response that does not exactly match the
      reference diagnosis of 120 [reparative changes]). RESULTS: Cases with a reference
      diagnosis of reparative changes made up 1.2% of all ThinPrep slides and 3.7% of
      all conventional slides in circulation. The false-positive discordancy rate of
      individual responses on educational slides for conventional smears was
      significantly higher than the corresponding false-positive discordancy rate for
      ThinPrep specimens (15.7% for conventional vs 7.1% for ThinPrep specimens, P <
      .001). Laboratory responses on educational conventional smears and ThinPrep
      slides showed a similar trend (14.2% for conventional smears vs 2.4% for ThinPrep
      slides, P = .002). The exact match error rate on educational conventional slides
      was 41.4% for individual responses, while on educational ThinPrep slides, the
      overall error rate was 57.5% (P < .001). For laboratory responses, the exact
      match error rate was 40.5% for educational conventional smears versus 58.9% for
      educational ThinPrep smears (P < .001). Characteristic features of reparative
      changes were identified in ThinPrep specimens. CONCLUSIONS: In the College of
      American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology,
      ThinPrep slides with a reference diagnosis of reparative changes have a lower
      false-positive discordancy rate than conventional slides. Responses to ThinPrep
      cases with a reference diagnosis of reparative change show a higher exact match
      error rate than conventional smears. Since reparative changes in gynecologic
      cytology are recognized as indicating an increased risk of significant lesions,
      the clinical significance of these altered patterns of recognition of reparative
      changes in ThinPrep specimens warrants further investigation.

PMID- 15974809
TI  - Protocol for the examination of specimens from pediatric and adult patients with
      osseous and extraosseous ewing sarcoma family of tumors, including peripheral
      primitive neuroectodermal tumor and ewing sarcoma.

PMID- 15974810
TI  - Protocol for the examination of specimens from patients with neuroblastoma and
      related neuroblastic tumors.

PMID- 15974812
TI  - Variability in cytologic-histologic correlation practices and implications for
      patient safety.
AB  - CONTEXT: The Clinical Laboratory Improvement Amendments of 1988 require that
      laboratories perform cytologic-histologic correlation, although the optimal
      methods and the value of performing correlation have not been determined.
      OBJECTIVE: To determine the similarities and differences in how laboratories
      perform cytologic-histologic correlation. DESIGN: One hundred sixty-two American
      laboratories were sent a letter requesting copies of the materials they used in
      the cytologic-histologic correlation process. The returned materials were
      classified into the categories of forms, logs, and tally sheets. A checklist
      (derived from the College of American Pathologists Laboratory Accreditation
      Cytopathology Checklist) was developed to classify the "minimum expected" (15)
      and "additional" data points that laboratories collected when they performed a
      correlation. PARTICIPANTS: American pathology laboratories. MAIN OUTCOME
      MEASURES: Measures were percentage of laboratories that recorded minimum expected
      and additional data points and the frequency with which specific minimum expected
      data points were recorded. RESULTS: The response frequency was 32.1%, and a total
      of 84 cytologic-histologic correlation materials were obtained. The only minimum
      expected variables recorded on forms or logs by more than 50% of laboratories
      were cytology case number, sign-out cytology diagnosis, surgical pathology case
      number, and sign-out surgical pathology diagnosis. Nine (17.3%) laboratories did
      not record data on forms, logs, or tally sheets. The mean number of minimum
      expected and additional variables recorded on forms was 6.5 and 8.7,
      respectively. CONCLUSIONS: Laboratories record data from the cytologic-histologic
      correlation process in a number of ways, indicating the lack of standardization
      of the data collection process.

PMID- 15974811
TI  - Distinguishing fibrovascular septa from vasculogenic mimicry patterns.
AB  - CONTEXT: Molecular analyses indicate that periodic acid-Schiff (PAS)-positive
      (laminin-rich) patterns in melanomas are generated by invasive tumor cells by
      vasculogenic mimicry. Some observers, however, consider these patterns to be
      fibrovascular septa, generated by a stromal host response. OBJECTIVE: To
      delineate differences between vasculogenic mimicry patterns and fibrovascular
      septa in primary uveal melanomas. DESIGN: Frequency distributions, associations
      with outcome, and thicknesses of trichrome-positive and PAS-positive looping
      patterns were determined in 234 primary uveal melanomas. Sequential sections of
      13 additional primary uveal melanomas that contained PAS-positive/trichrome
      negative looping patterns were stained for type I and type IV collagens, laminin,
      and fibronectin. Real-time quantitative polymerase chain reaction was performed
      on RNA from cultured uveal melanoma cells for the expression of COL1A1, COL4A2,
      and fibronectin. RESULTS: Trichrome-positive loops were encountered less
      frequently than PAS-positive loops (10% vs 56%, respectively). Death from
      metastatic melanoma was strongly associated with PAS-positive (P < .001) but not
      with trichrome-positive (P = .57) loops. Trichrome-positive loops were
      significantly thicker than PAS-positive loops (P < .001). The PAS-positive
      patterns stained positive for laminin, type I and type IV collagens, and
      fibronectin. Type I collagen was detected within melanoma cells and focally
      within some PAS-positive patterns. Real-time quantitative polymerase chain
      reaction revealed 3-fold, 25-fold, and 97-fold increases, respectively, in
      expression of COL4A2, fibronectin, and COL1A1 by invasive pattern-forming primary
      melanoma cells compared with poorly invasive non-pattern-forming cells.
      CONCLUSIONS: Fibrovascular septa are rare and prognostically insignificant in
      uveal melanomas, whereas vasculogenic mimicry patterns are associated with
      increased mortality. Type I collagen, seen focally in some vasculogenic mimicry
      patterns, may be synthesized by tumor cells, independent of a host stromal
      response.

PMID- 15974813
TI  - Atypical regenerative hyperplasia of the esophagus in endoscopic biopsy: a
      mimicker of squamous esophagic carcinoma.
AB  - CONTEXT: Atypical regeneration can mimic carcinoma in various epithelia. On
      endoscopic biopsies, atypical regenerative hyperplasia of the esophagus may show
      pleomorphism and atypia, simulating esophageal squamous cell carcinoma.
      OBJECTIVE: To establish the most useful histologic features to distinguish
      atypical regenerative hyperplasia from esophageal carcinoma in endoscopic
      biopsies. DESIGN: To study the frequency and histologic appearance of atypical
      regenerative hyperplasia, which simulate carcinoma, we reviewed 600 endoscopic
      biopsies (555 with chronic esophagitis and 45 with carcinomas of the esophagus).
      We selected those cases in which the differential diagnosis included regenerative
      atypical hyperplasia versus esophageal carcinoma and cases of atypical
      regenerative hyperplasia that were mistaken for carcinoma. For comparative
      purposes, we studied 10 cases of esophageal carcinoma from endoscopic biopsies
      that were confirmed by esophagectomy. RESULTS: Among the cases with chronic
      esophagitis, we found 10 biopsies (1.8%) in which atypical regenerative
      hyperplasia mimicked carcinoma. In 7 cases, there were 4 to 12 years of follow
      up, and no patient developed esophageal neoplasm. The remaining 3 patients were
      submitted to esophagectomy. None of these patients had carcinoma or dysplasia in
      the esophageal resection (false-positive biopsies). The most useful architectural
      changes in squamous carcinoma included stromal infiltration by nests, cords, or
      thin prongs of neoplastic keratinocytes, palisading desmoplasia, and in situ
      carcinoma in the adjacent epithelium. Malignant keratinocytes showed variable
      degrees of differentiation with differently shaped and sized cells, squamous
      epithelial pearls, individual keratinization, and atypical mitosis. In contrast,
      biopsies with atypical hyperplasia showed detached nests or irregular fragments
      without stroma and were made up of immature and relatively monotonous medium or
      small keratinocytes that were intermixed with inflammatory cells. Individual
      keratinization was rare, and no squamous pearls were seen. Other features of
      atypical hyperplasia included granulated tissue with atypical endothelial cells,
      nonatypical mitosis, lymphoid hyperplasia, and the absence of dysplasia or
      carcinoma in situ. Two biopsies showed stromal pseudoinfiltration as a result of
      tangential sectioning and were characterized by thick, round prongs composed of
      keratinocytes that penetrated regions with granulation or the inflamed tissues of
      esophageal ulcers. CONCLUSIONS: Atypical esophageal regenerative hyperplasia may
      mimic carcinoma in a small percentage of esophageal biopsies. If the histologic
      changes are not sufficient to establish an accurate diagnosis, medical treatment
      and subsequent biopsies should be performed, particularly if there are no
      endoscopic or radiologic data to support the presence of a neoplasm.

PMID- 15974814
TI  - Papillary carcinomas of the gallbladder: analysis of noninvasive and invasive
      types.
AB  - CONTEXT: Although papillary carcinomas have been recognized as distinct
      morphologic variants of gallbladder neoplasms, they have been lumped together in
      a single group despite the recognition of noninvasive and invasive types. As a
      result, the biologic behavior of each type remains undescribed. OBJECTIVE: To
      compare the biologic behavior of noninvasive and invasive papillary carcinomas of
      the gallbladder. DESIGN: The clinical and morphologic features of 16 noninvasive
      papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical
      behavior was compared with that of 370 invasive papillary carcinomas recorded in
      the Survey Epidemiology and End Results (SEER) Program of the National Cancer
      Institute from 1973 through 2001. The biologic behavior of invasive papillary
      carcinomas was compared with that of invasive nonpapillary carcinomas of the
      gallbladder recorded in SEER. Hematoxylin-eosin-stained sections were available
      for review in the 16 noninvasive papillary carcinomas. The number of slides
      examined per case varied from 3 to 16, with an average of 7. RESULTS: The 16
      patients with noninvasive papillary carcinomas included 11 women and 5 men, aged
      34 to 83 years (mean age, 61 years). Thirteen patients had cholelithiasis.
      Laparoscopic cholecystectomy was performed on 12 patients and open
      cholecystectomy on 4. The tumors measured from 1.3 to 8.6 cm and were well to
      moderately differentiated. Fourteen noninvasive papillary carcinomas showed
      biliary phenotype, and 2 showed intestinal phenotype. Follow-up was obtained in
      11 patients; 6 were asymptomatic 5 to 11 years after surgery, 2 were symptom free
      9 months to 4 years following cholecystectomy, and 3 died of unrelated causes 2
      to 3 years after surgery. Three hundred seventy cases of invasive papillary
      carcinomas were recorded in SEER. The 10-year relative survival rate for 225
      patients with invasive papillary carcinomas confined to the gallbladder wall was
      52%, while the 10-year relative survival rate for 83 patients with papillary
      carcinomas that had spread to the lymph nodes was less than 10%. Of the remaining
      62 invasive papillary carcinomas, 58 had distant metastases and 4 were not
      staged. The 10-year relative survival rate for invasive nonpapillary carcinomas
      confined to the gallbladder wall was 30%. CONCLUSION: Noninvasive papillary
      carcinomas of the gallbladder-regardless of size, cell phenotype, and degree of
      differentiation-do not metastasize, and a simple cholecystectomy appears to be a
      curative procedure. In contrast, invasive papillary carcinomas do metastasize and
      are associated with a poor prognosis (10-year relative survival rate for tumors
      confined to the gallbladder wall was 52%, while the 10-year relative survival
      rate for tumors with lymph node metastasis was <10%). The separation of papillary
      carcinomas into noninvasive and invasive types is clinically relevant and
      therefore fully justified.

PMID- 15974815
TI  - Incidental stromal-predominant mixed epithelial-stromal tumors of the kidney: a
      mimic of intraparenchymal renal leiomyoma.
AB  - CONTEXT: Mixed epithelial-stromal tumor of the kidney is a recently recognized
      benign renal tumor that usually occurs in adult women and typically forms a
      sizable lesion with solid and cystic areas. The recognized morphologic spectrum
      of this recently described entity is evolving. OBJECTIVE: To review the
      clinicopathologic features of 3 small mixed epithelial-stromal tumors of the
      kidney that were incidental findings in kidneys removed for other reasons.
      DESIGN: The clinical presentation and morphologic findings of the 3 cases were
      reviewed. A panel of immunohistochemical stains was performed. SETTING: Academic
      medical center. RESULTS: All 3 lesions contained predominantly fascicles of
      smooth muscle mimicking leiomyoma, but they also had cellular subpopulations of
      smaller, mullerian-appearing stromal cells. Tubules present within the lesion
      were most abundant at the periphery, suggesting that they might be entrapped.
      Although only the spindled smooth muscle cells were immunoreactive for muscle
      markers desmin and actin, both the spindled smooth muscle cells and the cellular
      mullerian-appearing stromal cells demonstrated diffuse nuclear labeling for
      estrogen and progesterone receptors. CONCLUSIONS: Mixed epithelial-stromal tumor
      of the kidney may present as an incidental stromal-predominant lesion within the
      kidney. Such lesions are easily confused with leiomyomas or stromal-predominant
      angiomyolipomas.

PMID- 15974816
TI  - Expression patterns of markers for type II pneumocytes in pulmonary sclerosing
      hemangiomas and fetal lung tissues.
AB  - CONTEXT: Although the histogenesis of sclerosing hemangioma is currently not well
      understood, the tumor has been characterized by its 2 histologically different
      types of cells, namely, surface and polygonal cells. OBJECTIVE: To elucidate the
      origin of these cells, we analyzed samples from 15 cases of sclerosing hemangioma
      and 15 specimens of fetal lung tissue. DESIGN: We immunostained specimens from 15
      cases of sclerosing hemangioma and 15 samples of fetal lung tissue using
      antibodies against thyroid transcription factor 1, MUC1, Thomsen-Friedenreich
      antigen, and CD44v6, known as markers for type II pneumocytes, and a panel of
      antibodies against cytokeratin, epithelial membrane antigen, synaptophysin, CD56,
      estrogen receptor, and progesterone receptor. RESULTS: In fetal lung tissue, MUC1
      and thyroid transcription factor 1 were expressed throughout all developmental
      stages of airway epithelium, whereas Thomsen-Friedenreich antigen and CD44v6 were
      expressed by type II pneumocytes of saccular and alveolar origin. Thomsen
      Friedenreich antigen was expressed in the bronchial bud of the pseudoglandular
      stage. MUC1, thyroid transcription factor 1, and epithelial membrane antigen were
      observed in both surface and polygonal cells of sclerosing hemangioma. Only the
      surface cells in all cases of sclerosing hemangioma showed positivity for
      cytokeratin and CD44v6. Thomsen-Friedenreich antigen was expressed in the surface
      cells of 11 of 15 cases of sclerosing hemangioma. Epithelial membrane antigen was
      expressed in both types of tumor cells, whereas cytokeratin was not detected on
      polygonal cells, but was reactive with surface cells. CONCLUSIONS: Our results
      suggest that the 2 types of cells in sclerosing hemangioma may derive from a
      common precursor cell through divergent differentiation toward the type II
      pneumocyte during tumorigenesis.

PMID- 15974817
TI  - Expression of the intestinal marker Cdx2 in secondary adenocarcinomas of the
      colorectum.
AB  - CONTEXT: Secondary adenocarcinomas of the large bowel can closely mimic primary
      tumors. The differentiation of secondary from primary adenocarcinomas of the
      colorectum, however, is important because their clinical management and prognosis
      are different. Immunostaining with the nuclear transcription factor Cdx2,
      expressed in normal intestinal epithelia and colorectal adenocarcinomas, could be
      of potential diagnostic use. OBJECTIVE: To investigate the diagnostic value of
      Cdx2 immunoexpression in distinguishing primary from common forms of secondary
      colorectal adenocarcinomas. DESIGN: Cdx2 immunoexpression was analyzed in 20
      primary colorectal adenocarcinomas and in 34 secondary colorectal adenocarcinomas
      and their corresponding primary tumors. All secondary tumors were diagnosed
      through endoscopic biopsies and included 8 cases of ovarian (4 serous, 2
      mucinous, and 2 endometrioid), 6 of mammary (4 lobular and 2 ductal), 4 of
      gastric (2 intestinal and 2 diffuse), 4 of pulmonary, 4 of pancreatic (ductal), 3
      of prostatic, 3 of colorectal, and 2 of endometrial origin. RESULTS: Cdx2 was
      expressed in normal colorectal epithelium, in primary colorectal adenocarcinomas
      (20/20 cases), in secondary adenocarcinomas of colorectal (3/3) and gastric (3/4)
      origin, and in metastatic ovarian mucinous adenocarcinomas (2/2). In contrast, no
      Cdx2 immunoreactivity was observed in secondary colorectal tumors of ovarian
      (serous and endometrioid), mammary, pancreatic, pulmonary, prostatic, and
      endometrial origin. CONCLUSION: Cdx2 immunostaining may be useful in
      discriminating primary colorectal carcinomas from frequent types of secondary
      colorectal adenocarcinomas of nongastrointestinal origin. We suggest including
      Cdx2 in any antibody panel put together to distinguish between primary and
      secondary epithelial colorectal malignancies.

PMID- 15974818
TI  - Allergic bronchopulmonary aspergillosis: an overview.
AB  - This article provides an overview of the major pathologic manifestations of
      allergic bronchopulmonary aspergillosis; patient characteristics; clinical,
      radiographic, and laboratory features of the disease; and current knowledge about
      its pathogenesis. Although allergic bronchopulmonary aspergillosis is an
      infrequent complication of asthma or cystic fibrosis, recognition of this
      disorder is important to avoid progression of bronchiectasis and lung parenchymal
      damage. Clinical, laboratory, and radiographic criteria allow for diagnosis of
      most cases, but the pathologist may encounter clinically unsuspected or atypical
      cases that require morphologic confirmation.

PMID- 15974819
TI  - Mantle cell lymphoma disguised as marginal zone lymphoma.
AB  - We report a case of mantle cell lymphoma histologically indistinguishable from
      marginal zone lymphoma. An 83-year-old man presented with a 9.0-cm, slowly
      enlarging axillary mass. Microscopically, the neoplastic process was largely
      interfollicular, surrounding residual follicular centers, some of which had
      discernible small lymphocyte mantles. Overall, the morphologic pattern was highly
      suggestive of marginal zone lymphoma. However, flow cytometric and
      immunohistochemical results, including cyclin D1 positivity, revealed an
      immunophenotype that fit with mantle cell lymphoma. The differential diagnosis of
      mantle cell lymphoma is broad, and it is well known that mantle cell lymphoma can
      assume a number of histologic appearances, including, infrequently, that of more
      indolent B-cell non-Hodgkin lymphomas. Although not pathognomonic, cyclin D1
      positivity is highly specific for mantle cell lymphoma and is key in
      distinguishing these clinically dissimilar malignant lymphomas. In recent years,
      detection of cyclin D1 has expanded the recognizable histologic spectrum of
      mantle cell lymphoma.

PMID- 15974820
TI  - Whipple disease: a case report and review of the literature.
AB  - Whipple disease is a chronic, relapsing, and multisystem disease. It presents a
      diagnostic challenge for both clinicians and pathologists. Recent advances in
      isolation and culture have identified the organism responsible for the disease to
      be a member of the order Actinomycetes designated Tropheryma whipplei. Several
      immune system changes have been noted in patients with Whipple disease, but
      whether these are primary or secondary is as yet undetermined. Long-term
      antibiotic therapy is required, and relapses are common, especially with central
      nervous system involvement.

PMID- 15974821
TI  - Patient with double bence jones proteinuria after hematopoietic cell
      transplantation.
AB  - About two thirds of patients with multiple myeloma and M-component in serum also
      have light chains in urine. However, the simultaneous presence of 2 Bence Jones
      proteins of different immunologic types in the same patient is rare. We describe
      the case of a 58-year-old woman with multiple myeloma, having 2 monoclonal light
      chains of both types (kappa and lambda) and an immunoglobulin G-lambda monoclonal
      protein in urine. The quantitative determination of light chains in urine was
      carried out using nephelometry, and Bence Jones proteinuria was confirmed by
      agarose gel immunofixation. To the best of our knowledge, this is the first
      reported case of double Bence Jones proteinuria after hematopoietic cell
      transplantation.

PMID- 15974822
TI  - Malignant glomus tumor of the urinary bladder.
AB  - We present a case of a malignant glomus tumor arising in the urinary bladder of a
      57-year-old woman with metastatic pulmonary nodules who died 2 months later.
      Pathologically and clinically confirmed malignant glomus tumors are exceedingly
      rare, especially those that arise in the visceral organs. The present case
      retained its architectural similarity to a benign glomus tumor and consisted of
      sheets of highly malignant round cells showing cytoplasmic positivity for smooth
      muscle actin. On reticulin histochemical staining, we found that reticulum
      fibrils surrounded individual tumor cells, suggesting cellular investment by
      basement membrane. We discuss the concept of malignant glomus tumors and
      emphasize the criteria that distinguish them from other malignant tumors.

PMID- 15974823
TI  - Intracardiac mass in a man infected with human immunodeficiency virus.

PMID- 15974824
TI  - A 53-year-old white man with right-sided supraclavicular lymphadenopathy.

PMID- 15974825
TI  - An 18-year-old man with abdominal pain, weight loss, and liver cyst.

PMID- 15974826
TI  - Lymphadenopathy in a 3-year-old boy 17 months after bone marrow transplantation
      for acute myeloid leukemia (AML-M5a).

PMID- 15974827
TI  - An 82-year-old woman with a 25-cm abdominal mass.

PMID- 15974828
TI  - A 75-year-old man with a solitary left orbital mass.

PMID- 15974829
TI  - A 72-year-old woman with papules and nodules at the site of previous mastectomy.

PMID- 15974830
TI  - A 44-year-old woman with intracranial hemorrhage.

PMID- 15974831
TI  - A neck mass in a 57-year-old man.

PMID- 15974832
TI  - A 37-year-old woman with dural-based intracranial masses.

PMID- 15974833
TI  - Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant
      system in turkish patients with type 2 diabetes mellitus.
AB  - Paraoxonase (PON1) is a serum enzyme with an antioxidant function, protecting the
      low density lipoproteins (LDL) from oxidative modifications. Because diabetic
      patients are at greater risk of oxidative stress, we investigated the effect of
      PON1 55 methione (M)/leucine (L) and PON1 192 glutamine (A)/arginine (B)
      polymorphisms on oxidant-antioxidant system in 213 individuals with type 2
      diabetes mellitus and 116 non-diabetic control subjects from Turkish population
      were included in the study. Polymerase chain reaction (PCR), restriction fragment
      length polymorphism (RFLP), and agarose gel electrophoresis techniques were used
      to determine the PON1 genotypes. Thiobarbituric acid reactive substances (TBARS),
      conjugated dienes levels in the serum and glutathione (GSH) levels in whole blood
      were measured spectrophotometrically. In both groups PON1 192 AA and PON1 55 MM
      genotypes had higher TBARS, conjugated dienes levels and lower GSH levels,
      whereas PON1 192 BB and PON1 55 LL genotypes had lower TBARS, conjugated diene
      levels and higher GSH level than other genotypes. We thus conclude that PON1 192
      BB and PON1 55 LL alleles have protective effect against oxidative stress.

PMID- 15974834
TI  - Does antinerve growth factor affect isolated ileal contractility in rat?
AB  - This study investigates the effects of antinerve growth factor (anti-NGF)
      application on isolated ileal contractility in the rat. For this purpose, rats
      were divided into four groups. The control animals (n=8) received only
      intraperitoneal injection of an isotonic NaCl solution (i.p). Anti-NGF was daily
      administered intraperitoneally at the dose of 1 ng/g level in the first
      experimental group (n=8), and at doses of 10 ng/g (n=7) and 40 ng/g (n=7) in the
      second and third experimental groups, respectively. Seven days after the
      injections rats were sacrificed and ileum segments were isolated. Responses to
      acetylcholine (ACh) were evaluated by using standard Tyrode, double-calcium
      Tyrode and calcium-free Tyrode solutions. The average peak amplitude of ACh
      induced contractions recorded in standard Tyrode solution was significantly
      decreased in all three experimental groups as compared to the control group (p
      0.05). When double-calcium Tyrode solution was used as the perfusion medium, the
      responses to ACh were also lower in all anti-NGF applied groups as compared to
      its control group (p 0.05). Our results showed that the application of anti-NGF
      reduced the contractile responses of the rat isolated ileum apparently by
      decreasing the calcium influx from the extracellular medium.

PMID- 15974835
TI  - Transient hypobaric hypoxia improves spatial orientation in young rats.
AB  - To achieve a better understanding of learning and declarative memory under mild
      transient stress, we investigated the effect of brief hypobaric hypoxia on
      spatial orientation in rats. Young male Wistar rats aged 30 days were exposed for
      60 min to hypobaric hypoxia, simulating an altitude of 7,000 m (23,000 ft) either
      shortly prior to attempting or after mastering an allothetic navigation task in
      the Morris water maze with a submerged platform. The post-hypoxic group performed
      significantly better in the navigation task than the control animals (the mean
      difference in escape latencies was 11 seconds; P=0.0033, two-way ANOVA with
      repeated measures, group x session). The experimental group also achieved a
      remarkably higher search efficiency (calculated as a percentage of successful
      trials per session), especially during the first four days following hypoxic
      stress (P=0.0018). During the subsequent training, the post-hypoxic group
      performed better than the control animals, whilst the efficiency levels of both
      groups progressively converged. Spatial memory retention and recall of well
      trained rats were not affected by the transient hypobaric hypoxia. These results
      indicate that brief hypobaric hypoxia enhances rats' spatial orientation. Our
      findings are consistent with several studies, which also suggested that mild
      transient stress improves learning.

PMID- 15974836
TI  - Experimental cauda equina compression induces HSP70 synthesis in dog.
AB  - The heat shock protein 70 (HSP70) is a key component of the stress response
      induced by various noxious conditions such as heat, oxygen stress, trauma and
      infection. In present study we have assessed the consequences of the compression
      of lower lumbar and sacral nerve roots caused by a multiple cauda equina
      constrictions (MCEC) on HSP70 immunoreactivity (HSP70-IR) in the dog. Our data
      indicate that constriction of central processes evokes HSP70 up-regulation in the
      spinal cord (L7, S1-Co3) as well as in the corresponding dorsal root ganglion
      cells (DRGs) (L7-S1) two days following injury. A limited number of bipolar or
      triangular HSP-IR neurons were found in the lateral collateral pathway (LCP) as
      well as in the pericentral region (lamina X) of the spinal cord. In contrast, a
      high number of HSP70 exhibiting motoneurons with fine processes appeared in the
      ventral horn (laminae VIII-IX) of lumbosacral segments. Concomitantly, close to
      them a few lightly HSP70-positive neuronal somata or cell bodies lacking the
      HSP70-IR occurred. In the DRGs, HSP70 expression was mildly up-regulated in small
      and medium-sized neurons and in satellite cells. On the contrary, DRGs from
      intact or sham-operated dogs did not reveal HSP70 specific neuronal staining. In
      conclusion, we have demonstrated that the MCEC in dogs mimicking the cauda equina
      syndrome in clinical settings evokes expression of HSP70 synthesis in specific
      neurons of the lumbo-sacro-coccygeal spinal cord segments and in small and medium
      sized neurons of corresponding DRGs. This suggests that HSP70 may play an active
      role in neuroprotective processes partly by maintaining intracellular protein
      integrity and preventing the neuronal degeneration in this experimental paradigm.

PMID- 15974837
TI  - Periodontal diseases and the risk of preterm birth and low birth weight: a meta
      analysis.
AB  - BACKGROUND: This meta-analysis of periodontal disease in relation to the risk of
      preterm birth/low birth weight (PTB/ LBW) is based on two case-control studies
      and three prospective cohort studies that met pre-stated inclusion criteria.
      METHODS: Information on the designs of the studies, characteristics of the study
      population, exposure and outcome measures, control for confounders, and risk
      estimates were abstracted independently by two investigators using a standard
      protocol. RESULTS: Pregnant women with periodontal disease had an overall
      adjusted risk of preterm birth that was 4.28 (95% confidence interval [CI], 2.62
      to 6.99; P <0.005) times that risk for healthy subjects. The overall adjusted
      odds ratio of preterm low birth weight was 5.28 (95% CI, 2.21 to 12.62; P
      <0.005), while the overall adjusted odds ratio of a delivery of either PTB or LBW
      was 2.30 (95% CI, 1.21 to 4.38; P <0.005). CONCLUSIONS: Our findings indicate
      that periodontal diseases in the pregnant mother significantly increase the risk
      of subsequent preterm birth or low birth weight. While it remains important to
      promote good oral hygiene during routine prenatal visits, there is no convincing
      evidence, on the basis of existing case control and prospective studies, that
      treatment of periodontal disease will reduce the risk of preterm birth.
      Consequently, large randomized, placebo-controlled, masked clinical trials are
      required.

PMID- 15974838
TI  - Apoptosis in cyclosporin A-induced gingival overgrowth: a histological study.
AB  - BACKGROUND: Cyclosporin A (CsA) is known to induce gingival overgrowth. Apoptosis
      plays a critical role in the regulation of inflammation and the host immune
      response. The aim of this study was to investigate apoptosis in CsA-induced
      gingival enlargement using electron microscopy examination of keratinocytes.
      METHODS: Gingiva specimens were collected from 12 CsA-treated renal transplant
      patients with gingival overgrowth and eight healthy controls with gingivitis.
      Clinical findings (probing depth, gingival index, and plaque index) were compared
      in the two groups. Histological and ultrastructural features of the specimens
      were also compared, and extent of keratinocyte apoptosis was scored on a three
      tier scale: 0 = no apoptotic cells; 1 = one or two apoptotic cells; 2 = more than
      two cells. RESULTS: There were no significant differences between groups with
      respect to gingiva-related clinical findings or extent of keratinocyte apoptosis.
      CONCLUSIONS: The results indicate that the extent of keratinocyte apoptosis in
      the gingiva of kidney recipients with CsA-induced gingival overgrowth is similar
      to that observed in inflamed gingiva of healthy individuals. Further studies on
      apoptosis of different cell types in the presence of CsA should clarify this
      agent's role in the pathogenesis of drug-induced gingival enlargement.

PMID- 15974839
TI  - Salivary Actinomyces naeslundii genospecies 2 and Lactobacillus casei levels
      predict pregnancy outcomes.
AB  - BACKGROUND: Gravida's poor periodontal health is emerging as a modifiable
      independent risk factor for preterm delivery and low birth weight. METHODS: To
      test the hypothesis that oral bacteria other than periodontal pathogens are also
      associated with pregnancy outcomes, specific oral bacterial levels measured
      during pregnancy were evaluated in relation to gestational age and birth weight
      while controlling for demographic, medical, and dental variables. The study
      population consisted of 297 predominantly African- American women who were
      pregnant for the first time. The salivary bacterial levels evaluated were
      Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinus,
      Lactobacillus acidophilus, Lactobacillus casei, Actinomyces naeslundii
      genospecies (gsp) 1 and 2, total streptococci, and total cultivable organisms.
      RESULTS: For 1 unit increase in log(10) A. naeslundii gsp 2 levels, there was a
      60 gm decrease in birth weight (beta = -59.7 g; SE = 29.1; P = 0.04), and a 0.17
      week decrease in gestational age (beta = -0.17 wk; SE = 0.09; P = 0.05). In
      contrast, per 1 unit increase in log(10) L. casei levels, there was a 42 gm
      increase in birth weight (beta = 42.2 g; SE = 19.3; P = 0.03), and a 0.13 week
      increase in gestational age (beta = 0.13 week; SE = 0.06; P = 0.04). CONCLUSIONS:
      We conclude that other oral bacterial species can also be related to pregnancy
      outcomes in addition to previously reported periodontal pathogens. These organism
      levels may not only predict poor pregnancy outcomes, but also be used as
      modifiable risk factors in reducing prematurity and low birth weight.

PMID- 15974840
TI  - Histologic evaluation of autogenous connective tissue and acellular dermal matrix
      grafts in humans.
AB  - BACKGROUND: The clinical success of root coverage with autogenous connective
      tissue (CT) or acellular dermal matrix (ADM) has been well documented. However,
      limited histological results of CT grafts have been reported, and a case report
      of a human block section has been published documenting an ADM graft. The purpose
      of this study is to document the histological results of CT grafts, ADM grafts,
      and coronally advanced flaps to cover denuded roots in humans. METHODS: This
      study included four patients previously treatment planned for extractions of
      three or more anterior teeth. Three teeth in each patient were selected and
      randomly designated to receive either a CT or ADM graft beneath a coronally
      advanced flap (tests) or coronally advanced flap alone (control). Six months
      postoperatively block section extractions were performed and the teeth processed
      for histologic evaluation with hematoxylin-eosin and Verhoeff's stains. RESULTS:
      Histologically, both the CT and ADM were well incorporated within the recipient
      tissues. New fibroblasts, vascular elements, and collagen were present throughout
      the ADM, while retention of the transplanted elastic fibers was apparent. No
      effect on the keratinization or connective tissue organization of the overlying
      alveolar mucosa was evident with either graft. For both materials, areas of
      cemental deposition were present within the root notches, the alveolar bone was
      essentially unaffected, and the attachments to the root surfaces were similar.
      CONCLUSION: Although CT and ADM have a slightly different histological
      appearance, both can successfully be used to cover denuded roots with similar
      attachments and no adverse healing.

PMID- 15974841
TI  - Effect of low-level Er:YAG laser irradiation on cultured human gingival
      fibroblasts.
AB  - BACKGROUND: Low-level laser irradiation has been reported to enhance wound
      healing. Activation of gingival fibroblasts (GF) has a potential for early wound
      healing in periodontal treatment. The present study aimed to investigate the
      direct effect of low-level Er:YAG laser irradiation on gingival fibroblasts
      proliferation in order to clarify the laser effect on healing. METHODS: Cultured
      human gingival fibroblasts (hGF) were exposed to low-power, pulsed Er:YAG laser
      irradiation with different energy densities ranging from 1.68 to 5.0 J/cm(2). The
      cultures were analyzed by means of trypan blue staining and counted under a light
      microscope. The effect of Er:YAG laser on hGF was also evaluated using a
      transmission electron microscope (TEM). RESULTS: Cultures irradiated with Er:YAG
      laser presented faster cell growth when compared with untreated controls. This
      difference was statistically significant. Transmission electron microscopy
      revealed rough endoplasmic reticulum, prominent Golgi complexes, and mitochondria
      after laser irradiation. CONCLUSIONS: Our results showed that the low-level
      Er:YAG laser irradiation stimulates the proliferation of cultured gingival
      fibroblasts. The optimal stimulative energy density was found to be 3.37 J/cm(2).
      This result suggests that Er:YAG laser irradiation may be of therapeutic benefit
      for wound healing.

PMID- 15974842
TI  - Capnocytophaga spp. in periodontitis patients manifesting diabetes mellitus.
AB  - BACKGROUND: The subgingival microflora in patients presenting concurrently with
      periodontitis and diabetes mellitus (DM) are poorly understood. While traditional
      putative periodontal pathogens are implicated, research involving other oral
      organisms; e.g., Capnocytophaga spp., is lacking. These organisms produce a range
      of bacterial enzymes relevant to periodontal breakdown. It is inferred that
      periodontal bacteria acquire systemic access through the ulcerated periodontal
      pocket surface; conclusive evidence supporting this notion is limited. The aims
      of this investigation were to: 1) quantify and identify Capnocytophaga spp.
      present in healthy and diseased sites in periodontitis patients with and without
      DM, and 2) isolate periodontal pathogens from these patients' blood. METHODS:
      Twenty-one DM-periodontitis and 25 periodontitis patients were recruited.
      Subgingival plaque was collected from three healthy and three diseased sites per
      subject. Capnocytophaga spp. and total (facultative and obligate) anaerobic
      counts from each site were estimated. Capnocytophaga spp. were identified using
      16S rRNA polymerase chain reaction (PCR) restriction fragment length polymorphism
      (RFLP). Statistical analyses were performed using multilevel modeling. Blood
      samples were subjected to HbA(1c) estimation and bacterial culture. RESULTS: A
      total of 848 Capnocytophaga spp. were isolated and identified. Significantly
      higher numbers of Capnocytophaga spp. (P <0.001) and anaerobes (P <0.001) were
      present in diseased sites in DM-periodontitis subjects compared to healthy sites
      in non-DM-periodontitis and DM-periodontitis subjects. C. ochracea (and variant)
      and C. granulosa were the most prevalent species. Blood samples were negative for
      Capnocytophaga spp. CONCLUSIONS: Total mean counts for Capnocytophaga spp. were
      significantly higher in DM-periodontitis subjects versus non-DM-periodontitis (P
      = 0.025) and at diseased sites versus healthy sites (P <0.001). Analysis of
      individual species revealed that the outcome varied with site status and DM
      status.

PMID- 15974843
TI  - Detection of Actinobacillus actinomycetemcomitans in unstimulated saliva of
      patients with chronic periodontitis.
AB  - BACKGROUND: The use of whole saliva has shown to be promising in detecting
      Actinobacillus actinomycetemcomitans out of the subgingival environment. The
      objective of the present study was to evaluate the use of unstimulated saliva in
      detecting A. actinomycetemcomitans and to compare the subgingival and
      extracrevicular occurrence of this pathogen in Brazilian subjects with chronic
      periodontitis. METHODS: Sixty-six patients (mean age 38.01 9.28 years) with
      advanced generalized chronic periodontitis were sampled. Subgingival plaque
      samples were collected from eight sites per patient representing the two deepest
      sites of each quadrant. Samples of the mucous surfaces, including dorsal surface
      of the tongue and cheek, were collected with a sterile swab and placed in a
      microtube containing a reduced solution. Samples of unstimulated saliva were also
      collected in sterile tubes and 0.1 ml of whole saliva was diluted in 1 ml of
      reduced solution. The presence of A. actionomycetemcomitans was established using
      bacterial culture in trypticase soy bacitracin vancomycin selective media.
      Polymerase chain reaction (PCR) was used to differentiate highly from minimally
      leukotoxic strains in patients who presented A. actinomycetemcomitans in at least
      two sampled sites. RESULTS: A. actinomycetemcomitans was isolated from 63.63% of
      subgingival samples, 56.06% of saliva samples, and 45.45% of samples from mucous
      surfaces. No statistical difference was observed between subgingival and salivary
      occurrence of the microorganism. Linear regression showed an association between
      subgingival plaque and saliva (r(2) = 0.897; P = 0.015) and mucous membrane and
      saliva (r(2) = 0.152; P = 0.024). The same A. actinomycetemcomitans leukotoxic
      profile was observed in all sampled sites for a given patient. CONCLUSION: These
      results suggest that in advanced periodontitis, unstimulated saliva is
      representative of pooled subgingival plaque samples and its use is appropriate in
      the oral detection of A. actinomycetemcomitans.

PMID- 15974844
TI  - Evaluation of recombinant human bone morphogenetic protein-2 on the repair of
      alveolar ridge defects in baboons.
AB  - BACKGROUND: The objective of this study was to evaluate alveolar ridge
      augmentation following surgical implantation of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) using two novel space-providing carrier
      technologies in the baboon (Papio anubis) model. METHODS: Standardized alveolar
      ridge defects ( approximately 15 x 8 x 5 mm) were surgically produced in
      maxillary and mandibular edentulous areas in four baboons. The defect sites were
      implanted with rhBMP-2 (0.4 mg/mL) in a tricalcium phosphate/hydroxyapatite/
      absorbable collagen sponge composite (TCP/HA/ACS) or calcium phosphate cement
      (alpha-BSM). Control treatments were TCP/HA/ACS and ?-BSM without rhBMP-2 and
      sham surgery. Stainless steel pins were placed at the mid-apical and coronal
      level of the defect sites to provide landmarks for clinical measurements pre- and
      post-implantation. Impressions were obtained pre- and postimplantation to
      determine changes in alveolar ridge volume. Radiographic registrations were
      obtained pre- and post-implantation. Block sections of the defect sites were
      harvested at week 16 postimplantation and processed for histometric analysis
      including new bone area and bone density. Statistical comparisons between
      treatments were made using a mixed effect generalized linear model using least
      squares estimation. RESULTS: The carrier systems without rhBMP-2 provided a
      modest ridge augmentation. The addition of rhBMP-2 resulted in an almost 2-fold
      increase in alveolar ridge width, including a greater percentage of trabecular
      bone and a higher bone density compared to controls (P < or =0.05) without
      significant differences between the two rhBMP-2 protocols. CONCLUSIONS:
      TCP/HA/ACS and alphaBSM appear to be suitable carrier technologies for rhBMP-2.
      Alveolar augmentation procedures using either technology combined with rhBMP-2,
      rather than stand-alone therapies, may provide clinically relevant augmentation
      of alveolar ridge defects for placement of endosseous dental implants.

PMID- 15974845
TI  - Effect of locally delivered doxycycline hyclate on human fibroblast attachment to
      subgingival calculus.
AB  - BACKGROUND: Clinical studies using locally applied doxycycline hyclate (DHV) have
      demonstrated significant probing depth reduction and gain in clinical attachment
      as a monotherapy without scaling and root planing. The mechanism for this
      attachment level gain to the non-root planed tooth is not understood. The purpose
      of this study was to investigate the effect of locally applied doxycycline
      hyclate on human gingival fibroblast attachment to subgingival calculus on
      contaminated root surfaces. METHODS: Two separate experiments were performed,
      both on subgingival calculus. In experiment 1, teeth with subgingival calculus
      were treated with either doxcycycline hyclate in bioabsorbable vehicle (DHV) or
      with vehicle control (VC) in vivo. In experiment 2, teeth with subgingival
      calculus were treated with DHV, VC, scaling and root planing (SRP), or no
      treatment in vitro. The amount of cell attachment to calculus-covered root
      surfaces was quantitatively compared using a fluorescent dye assay and
      epifluorescence microscope. Values for cell attachment are presented as the mean
      standard deviation of the mean. The data were evaluated using Student t test.
      RESULTS: In both experiments, there was no statistically significant difference
      in fibroblast attachment in the DHV, VC, or no treatment groups (P >0.05). The
      SRP group showed significantly more cellular attachment to tooth surfaces
      formerly covered by subgingival calculus than all other groups (P <0.001). In
      general, more cells attached to cementum than to calculus. Root chips that showed
      no attachment to the subgingival calculus also had no cells attached to the
      adjacent cemental root surface. CONCLUSION: The addition of doxycycline hyclate
      in a bioabsorbable vehicle used as a locally delivered drug did not enhance the
      initial cellular attachment of human gingival fibroblasts to subgingival calculus
      or contaminated root surfaces.

PMID- 15974846
TI  - Experimental arthritis in rats induces biomarkers of periodontitis which are
      ameliorated by gene therapy with tissue inhibitor of matrix metalloproteinases.
AB  - BACKGROUND: Periodontal disease (PD) and rheumatoid arthritis (RA) share many
      common pathophysiologic features, but a clinical relationship between the two
      conditions remains controversial, in part because of the confounding effects of
      anti-inflammatory drug therapy universally used in the latter disease. To further
      explore this issue, inflammatory arthritis was induced in rats to determine the
      effect on gingival biomarkers of inflammation and tissue destruction and to
      investigate the effect of a therapeutic intervention devoid of conventional anti
      inflammatory properties. METHODS: Adjuvant arthritis (AA) was induced in Lewis
      male rats by injecting mycobacterium cell wall in complete Freund's adjuvant
      using standard techniques. One group of animals was treated by induction of
      systemic tissue inhibitor of matrix metalloproteinases (TIMP-4). At 3 weeks,
      arthritis severity was recorded and both paw and gingival tissues were collected
      for matrix metalloproteinase activity (MMP) and cytokine analysis. In addition,
      the maxillary jaws were removed for assessment of periodontal bone loss. RESULTS:
      The development of arthritis was associated with elevated joint tissue MMPs,
      tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta levels compared to
      control rats. In the gingival tissue of the untreated arthritic rats, gelatinase,
      collagenase, TNF-alpha, and IL-1beta were also elevated compared to control rats.
      Periodontal bone loss and tooth mobility were also increased significantly (P
      <0.05) in untreated arthritic rats. All parameters improved after TIMP-4 gene
      therapy. CONCLUSIONS: To our knowledge, this is the first study to report an
      association between experimental systemic arthritis in rats and elevated gingival
      tissue MMPs, cytokine levels, and periodontal disease. Reversal of these changes
      with TIMP-4 gene therapy strengthens the pathophysiologic correlation between
      systemic and local disease.

PMID- 15974847
TI  - Association of interleukin-1 polymorphisms with periodontal disease.
AB  - BACKGROUND: Several studies have investigated genetic polymorphisms for cytokines
      as potential genetic markers for periodontitis. Some studies have found that
      interleukin (IL)-1A and IL-1B polymorphisms are associated with a higher severity
      of periodontitis, while others found no association. The aims of this study were
      to determine the prevalence of the IL-1A-889 and IL-1B+3954 (previously described
      as +3953) polymorphisms in Chileans and their association with periodontitis.
      METHODS: Subjects aged 20 to 48 were selected from people requesting dental
      treatment at a public health center in Santiago, Chile. A case-control study of
      330 cases of periodontitis patients and 101 healthy controls was performed. A
      full-mouth periodontal examination was performed on each subject and a structured
      questionnaire was conducted to determine smoking habits. Cases were categorized
      as having initial, moderate, or severe periodontitis according to the percentage
      of sites with clinical attachment loss > or =3 mm. Genomic DNA was analyzed for
      polymorphism in the IL-1A gene at site -889 and IL-1B gene at site +3954 by
      polymerase chain reaction (PCR) amplification followed by restriction enzyme
      digestion and gel electrophoresis. Data were analyzed by chi square test,
      analysis of variance (ANOVA), and by calculating odds ratio (OR) and 95%
      confidence intervals (CI). RESULTS: Demographic and socio-economic
      characteristics of subjects were similar in cases and in controls. A higher
      frequency of heterozygous of the IL-1A-889 was found in cases than in controls,
      but the difference was not significant. The heterozygous of the IL-1B+3954 was
      significantly higher in cases than in controls and was associated with
      periodontitis (OR 3.12, 95% CI 1.59 to 6.09, P = 0.001). The homozygous for
      allele 1 of the IL-1B+3954 was a protective factor for periodontitis (OR 0.35,
      95% CI 0.19 to 0.66, P = 0.001). The prevalence of positive genotype (at least
      one allele 2 present at each locus) was significantly higher in cases (26.06%)
      than in controls (9.9%) and was significantly associated with periodontitis (OR
      3.21, 95% CI 1.60 to 6.44, P = 0.001), irrespective of the smoking status and
      periodontitis severity. Sensitivity of positive genotype was 26%, the specificity
      90%, and the positive predictive value 89%. CONCLUSION: Within the limits of this
      study, the results show that individuals carrying the positive genotype have
      significantly greater risk for developing periodontitis.

PMID- 15974849
TI  - FcgammaRIIIb genotypes and smoking in periodontal disease progression among
      community-dwelling older adults in Japan.
AB  - BACKGROUND: FcgammaRIIIb genotypes and smoking are risk factors for periodontal
      disease. However, the interaction of FcgammaRIIIb- NA1-NA2 polymorphism with
      smoking remains unclear. The purpose of this study was to determine if
      FcgammaRIIIb-NA1-NA2 polymorphism and smoking are associated with periodontal
      disease progression among elderly people. METHODS: Among 70-year-old subjects,
      164 with neither diabetes mellitus nor blood sugar > or =140 mg/dl, who had more
      than 20 teeth and who could participate in both the baseline and the follow-up
      examinations were included in the study. The NA1 group comprised subjects with
      FcgammaRIIIb-NA1NA1 genotype (N = 53), while the NA2 group included subjects with
      FcgammaRIIIb-NA1NA2 or NA2NA2 genotype (N = 111). We examined the progression of
      periodontitis by measuring attachment loss during 3 years. RESULTS: The frequency
      of subjects who showed > or =4 mm additional attachment loss at one or more sites
      was 55.6% for smokers and 37.2% for non-smokers. The odds ratio (OR) was 2.13
      (confidence interval [CI]: 0.92 to 4.76). We found a better association between
      periodontal progression and smoking in the NA2 group. The OR for smokers was 3.03
      (CI:1.12 to 8.33, P = 0.028). Additionally, the mean number of sites with > or =4
      mm additional attachment loss per person between smokers and non-smokers in the
      NA2 group or between smokers and non-smokers in the NA1 group was 2.90 3.42 and
      0.74 1.53 or 0.57 0.79 and 0.68 1.03, respectively (P <0.001; analysis of
      variance [ANOVA]). CONCLUSION: Our results may suggest an association between
      smoking and periodontal disease progression in elderly people with FcgammaRIIIb
      NA2 polymorphism.

PMID- 15974848
TI  - Enamel matrix derivative stimulates core binding factor alpha1/Runt-related
      transcription factor-2 expression via activation of Smad1 in C2C12 cells.
AB  - BACKGROUND: Although enamel matrix derivative (EMD) can promote osteogenic
      differentiation of the pluripotent mesenchymal precursor cell line, C2C12, the
      molecular mechanism that underlies this phenomenon is unclear. The purpose of
      this study was to determine which molecules in EMD stimulate osteogenic
      differentiation. METHODS: C2C12 cells were cultured in 5% serum-containing medium
      to induce differentiation, either with or without the addition of EMD. The
      expression of core binding factor alpha1/runtrelated transcription factor-2
      (Cbfa1/Runx2) was measured using Northern blot, Western blot, and/or real-time
      polymerase chain reaction (R-PCR) analysis. Phosphorylation of mothers against
      decapentaplegic homolog 1 (Smad1) and bone morphogenetic protein (BMP)-like
      molecules in EMD was determined by Western blot. RESULTS: EMD increased
      Cbfa1/Runx2 mRNA and protein expression substantially. EMD also induced
      phosphorylation of Smad1. Noggin inhibited the EMD-induced phosphorylation of
      Smad1 markedly, and also partially blocked EMD-induced Cbfa1/ Runx2 mRNA
      expression. In the Western blot analysis, single bands that corresponded to
      approximately 15 and approximately 17.5 kDa proteins were recognized in EMD by
      anti-BMP-2/4 and anti-BMP-7 antibodies, respectively. CONCLUSIONS: Our study
      demonstrates that EMD stimulates Cbfa1/Runx2 expression and the phosphorylation
      of Smad1, and that both of these processes can be blocked by noggin. Therefore,
      the osteogenic activity of EMD may be mediated by BMPlike molecules in EMD.

PMID- 15974850
TI  - Non-surgical periodontal therapy of shallow gingival recession defects:
      evaluation of the restorative capacity of marginal gingiva after 12 months.
AB  - BACKGROUND: There is a large amount of data on surgical root coverage procedures
      for the treatment of gingival recessions but no controlled clinical trials on the
      behavior of marginal gingiva following non-surgical therapy. The aim of our study
      was to compare in terms of root coverage two different modalities of root surface
      treatment, root planing and polishing versus polishing alone, over a 12-month
      period. METHODS: The study was conducted in a split-mouth design. Twenty-four non
      smoking patients (14 females and 10 males, mean age 25.17 4.03 years) with high
      levels of oral hygiene (full-mouth plaque score <20%) and with two bilateral
      Class I buccal recessions up to 2 mm deep were selected for the study. In each
      patient one recession was randomly assigned to the test group and the contra
      lateral one to the control group. In the test group the exposed root surface was
      gently debrided and polished with mini curets and mini rubber cups, while the
      control group was polished only. The root surface instrumentation was repeated
      twice a month during the first 2 months and at 2-month intervals over the next 10
      months. Clinical measurements were taken at baseline and 12 months post-therapy.
      RESULTS: At baseline the mean recession depth in the test group was 1.64 +/- 0.37
      mm and in the control sites 1.43 +/- 0.42 mm, which decreased at 12 months to
      0.78 +/- 0.60 mm and to 1.34 +/- 0.45 mm, respectively. The difference between
      the two groups was significant (P <0.0001). No significant differences were
      observed in keratinized tissue width and probing depth improvements. CONCLUSIONS:
      The removal of microbial toxins from the exposed root surfaces by polishing
      prevents further progression of gingival recession; the reduction of root
      convexity by scaling and root planing promotes the coronal shift of the gingival
      margin.

PMID- 15974851
TI  - Effect of partial recording protocols on estimates of prevalence of periodontal
      disease.
AB  - BACKGROUND: The aim of this study was to assess the degree of underreporting in
      the estimates of prevalence of periodontal attachment loss due to different
      partial recording protocols (PRP) in epidemiological studies, and to derive a
      correction factor to adjust for this bias. METHODS: The study sample included
      1,460 dentate persons 14 to 103 years old who were examined clinically to assess
      the clinical attachment loss at six sites per tooth. Seven PRP based on full
      mouth or half-mouth designs were assessed, and the bias and sensitivity in the
      assessment of attachment loss prevalence for these protocols were assessed.
      RESULTS: All partial protocols underestimated the prevalence of attachment loss.
      Bias estimates for any full-mouth PRP were smaller than those for the
      corresponding site-combination PRP for the half-mouth design. The PRP using the
      mesio-buccal (MB), mid-buccal (B), and disto-lingual (DL) sites of teeth in all
      four quadrants showed the smallest bias and highest sensitivity of prevalence
      estimates among the seven PRP evaluated, uniformly across the range of attachment
      loss severity level. The three site PRP incorporating the DL site produced less
      bias than the three site PRP including the disto-buccal (DB) site. There was a 3%
      to 12% gain in sensitivity for 2 to 5 mm attachment loss thresholds for the three
      site half-mouth PRP compared with the two site MB, B half-mouth PRP. CONCLUSIONS:
      The bias in the assessment of attachment loss is influenced by the partial
      recording design and the type and number of sites assessed, and is also
      influenced by the severity of attachment loss in the study population. These
      factors should be considered when selecting a partial recording method in large
      surveys. Furthermore, inflation factors designed to adjust for the bias due to
      the use of partial systems should be calculated and reported so that comparisons
      of results with other surveys are more meaningful.

PMID- 15974852
TI  - A pilot study applying digital radiography for estimating ratio of supported
      single-root surface area.
AB  - BACKGROUND: The prognosis of a tooth with periodontitis is affected by the amount
      of supporting bone. A key factor in retaining a tooth is the ratio of supported
      root surface. Currently, root surfaces cannot be accurately measured using
      conventional dental radiographs, which only measure the length of bone support on
      proximal surfaces. METHODS: Eight extracted, single-rooted teeth were 3
      dimensionally digitized using a contact technique for true surface area
      measurements. Root length, projection area, and pixel values were then measured
      on digital radiographs. The accuracy of the ratio estimation of supported surface
      area from linear, area, and pixel values was calculated and compared. RESULTS:
      The mean error from linear estimation was 7.9%; the mean error from area
      estimation was 1.0%; and the mean error from pixel value estimation was 1.3%. One
      way analysis of variance (ANOVA) showed significant differences in all
      estimations while Scheffe's analysis further revealed significant differences
      only in the linear estimation. CONCLUSIONS: A three-dimensional digitizing device
      could be used as a non-destructive method of measuring root surface area. The
      ratio of supported single-root surface area could be estimated with high accuracy
      from the projected area data acquired on the digital dental radiographs. The
      thickness data as reflected from the pixel values in the digital images did not
      improve the estimation accuracy. Estimations using only length data yielded
      significantly less accuracy. Digital dental x-ray images provide the potential
      for estimating the ratio of supported root surface efficiently.

PMID- 15974853
TI  - Proliferation of fibroblasts cultured from normal gingiva and hereditary gingival
      fibromatosis is dependent on fatty acid synthase activity.
AB  - BACKGROUND: Fatty acid synthase (FAS) is the enzyme that synthesizes palmitate
      from malonyl-CoA and acetyl-CoA. Recent studies have shown that FAS is
      overexpressed in human cancers and that its activity is necessary for cell
      proliferation. Hereditary gingival fibromatosis (HGF) is a genetic disease
      manifested as a progressive enlargement of the gingiva. The pathogenesis of this
      condition is not understood; however, a proliferative advantage of HGF
      fibroblasts in comparison with cells from normal gingiva (NG) has been described.
      The aim of this study was to investigate the role of FAS in NG and HGF fibroblast
      proliferation. METHODS: NG and HGF fibroblasts had their proliferative potential
      assessed by automated cell counting and immunocytochemistry against Ki-67 or
      proliferating cell nuclear antigen (PCNA). The production of FAS, androgen
      receptor (AR), and ErbB2 was analyzed by Western blot and the pattern of FAS
      expression studied by immunocytochemistry. FAS activity was blocked by the
      specific inhibitor cerulenin. RESULTS: Higher proliferation rates were found in
      fibroblasts isolated from HGF than from NG. HGF fibroblasts with greater
      proliferative potential produced more FAS and AR than the cell lines with lower
      growth rates, and all studied cell lines produced similar amounts of the ErbB2
      protein. In addition, the FAS inhibitor cerulenin was able to significantly
      reduce the proliferation of both NG and HGF cells. CONCLUSIONS: These results
      show that FAS is expressed by gingival fibroblasts and that highly proliferative
      HGF cells produced more FAS and AR than the other fibroblast cell lines.
      Moreover, FAS inhibition significantly reduced both NG and HGF fibroblast growth,
      suggesting a role for the androgen-driven fatty acid biosynthesis in their
      proliferation.

PMID- 15974854
TI  - Quantitative measures of aggressive periodontitis show substantial heritability
      and consistency with traditional diagnoses.
AB  - BACKGROUND: Aggressive periodontitis (AgP) research nearly always classifies
      subjects into traditional discrete categories of localized or generalized, based
      upon degree of attachment loss (AL) and types of affected teeth. Since AL is
      continuous and quantitative, however, useful information is lost. We developed
      quantitative measures of AgP, compared these to traditional methods, and
      estimated heritabilities in families. METHODS: We examined 237 healthy, 169
      localized AgP, and 204 generalized AgP subjects. We used the site of maximum AL
      of each tooth to calculate means for each subject for different groups of teeth.
      We also applied principal components analysis (PCA) to condense variation among
      28 teeth into three orthogonal (uncorrelated) variables. We used discriminant
      function analysis (DFA) to evaluate how well the quantitative measures match with
      traditional classifications. Quantitative trait heritabilities were estimated by
      variance components. RESULTS: PCA clustered first molars, incisors, and the other
      teeth into three groups. DFA showed that quantitative measures classified
      subjects consistent with traditional methods (87% to 94% agreement).
      Heritabilities ranged from 13.7% (P = 0.10) to 30.0% (P = 0.008) for quantitative
      measures, with highest values obtained for first molars. A combination of the
      principal component variables most heavily weighted on first molars and incisors
      gave the best model of disease susceptibility, with good separation of healthy
      versus diseased subjects, independent of disease extent or severity. CONCLUSIONS:
      Quantitative measures may provide improved precision and power for many kinds of
      periodontal research. Our finding of significant heritability supports their use
      in gene mapping studies of AgP susceptibility.

PMID- 15974855
TI  - Prevalence of periodontopathic bacteria in aggressive periodontitis patients in a
      Chilean population.
AB  - BACKGROUND: Actinobacillus actinomycetemcomitans is considered a major etiologic
      agent of aggressive periodontitis (AgP). Other periodontopathic bacteria such as
      Porphyromonas gingivalis are also suspected of participating in aggressive
      periodontitis although the evidence to support this is controversial. The aim of
      the present study was to determine the prevalence of eight periodontopathic
      bacteria in Chilean patients with AgP. METHODS: Subgingival plaque samples were
      collected from 36 aggressive, 30 localized, and six generalized periodontitis
      patients. Samples from 17 advanced chronic periodontitis (CP) patients were taken
      as controls. Samples collected from the four deepest periodontal pockets in each
      patient were pooled in prereduced transport fluid (RTF) and cultured. Periodontal
      bacteria were primarily identified by colony morphology under stereoscopic
      microscope and rapid biochemical tests. The identity of some bacterial isolates
      was confirmed by colony polymerase chain reaction (PCR). RESULTS: AgP showed a
      significatively higher prevalence of C. rectus than CP (P = 0.036). The only
      statistical difference found was for C. rectus. Patients with AgP showed a
      higher, but not statistically significant, prevalence of P. gingivalis, E.
      corrodens, P. micros, and Capnocytophaga sp. A similar prevalence in both groups
      of patients was observed for F. nucleatum and P. intermedia/nigrescens, and A.
      actinomycetemcomitans was less prevalent in AgP than CP patients. In localized
      AgP, P. intermedia/nigrescens, E. corrodens, F. nucleatum, and P. micros were the
      more prevalent pathogens in contrast to generalized AgP patients who harbored A.
      actinomycetemcomitans, P. gingivalis, and Capnocytophaga sp. as the most
      prevalent bacteria. CONCLUSIONS: C. rectus, P. gingivalis, E. corrodens, P.
      micros, and Capnocytophaga sp. were the most predominant periodontopathic
      bacteria of AgP in this Chilean population, but the only statistical difference
      found here between AgP and CP was for C. rectus, suggesting that the differences
      in clinical appearance may be caused by factors other than the microbiological
      composition of the subgingival plaque of these patients. In this study, the
      prevalence of A. actinomycetemcomitans was much lower than that of P. gingivalis.

PMID- 15974856
TI  - Simvastatin promotes cell metabolism, proliferation, and osteoblastic
      differentiation in human periodontal ligament cells.
AB  - BACKGROUND: Simvastatin is one of the cholesterol lowering drugs. Recent studies
      demonstrated that it has a bone stimulatory effect. Periodontal ligament (PDL)
      cells are believed to play an important role in periodontal regeneration; that
      is, they may differentiate into specific cells which make cementum, bone, and
      attachment apparatus. It would be of interest whether simvastatin has a positive
      effect on PDL cells. Therefore, effects of simvastatin on cell proliferation and
      osteoblastic differentiation in PDL cells were analyzed. METHODS: Human PDL cells
      were cultured in monolayer with simvastatin for 24 and 72 hours and cell
      metabolism and proliferation were determined. To analyze osteoblastic
      differentiation, human PDL cells were cultured in organoid culture for 7, 14, and
      21 days and alkaline phosphatase (ALP) activity, osteopontin (OPN), bone
      morphogenetic protein (BMP) -2, osteocalcin (OCN), and calcium contents were
      measured. They were co-treated by simvastatin and mevalonate. RESULTS:
      Simvastatin enhanced cell proliferation and metabolism dose-dependently after 24
      hours. Simvastatin also stimulated ALP activity of human PDL cells dose
      dependently, and maximum effect was obtained at the concentration of 10(8) M. In
      time dependent analysis, 10(8) M simvastatin stimulated ALP activity and
      osteopontin content after 7 days and calcium contents after 21 days. BMP-2 and
      OCN contents were not detected. Moreover this statin-enhanced ALP activity was
      abolished by mevalonate. CONCLUSION: These results suggest that at low
      concentration, simvastatin exhibits positive effect on proliferation and
      osteoblastic differentiation of human PDL cells, and these effects may be caused
      by the inhibition of the mevalonate pathway.

PMID- 15974857
TI  - Prostaglandins E(2) and F(2alpha) enhance differentiation of cementoblastic
      cells.
AB  - BACKGROUND: The prostaglandins (PG) E(2) and PGF(2alpha) are important cytokines
      in periodontal physiology and pathology. PGE(2) and PGF(2alpha) alter cell
      function by binding and activating the plasmamembrane G-protein-coupled PG
      receptors. In this study, we examined the PGE(2) and PGF(2alpha) effects on the
      immortalized cementoblastic OCCM cells. METHODS: Confluent OCCM cells were
      treated with PGE(2), PGF(2alpha), specific activators/inhibitors of the EP
      prostanoid receptors, a specific activator of the FP prostanoid receptor, and
      direct activators/inhibitors of the protein kinase C (PKC) signaling pathway.
      Mineral nodule formation was assessed by the von Kossa stain. RESULTS: PGE(2) and
      PGF(2alpha) significantly increased mineralization of OCCM cells. The EP1 and EP3
      PG receptor activators 16,16-dimethyl-prostaglandin E(2) and sulprostone, also
      increased mineralization. In contrast, specific activators of the EP2 or the
      EP2/EP3/EP4 receptors did not have any effect. Fluprostenol, a specific activator
      of the FP receptor, significantly increased mineralization of OCCM cells. FP and
      EP (1 or 3) receptors signal through activation of the protein kinase C (PKC)
      pathway. Indeed, phorbol 12-myristate 13-acetate (PMA), a direct activator of the
      PKC pathway, significantly increase OCCM mineralization, while pre-treatment of
      OCCM cells with the PKC inhibitor GF109203x (bisindolylmaleimide) significantly
      decreased mineralization. CONCLUSION: We conclude that PGE(2) and PGF(2alpha)
      exert an anabolic effect on OCCM mineralization through activation of PKC
      signaling.

PMID- 15974858
TI  - Osseointegrated dental implants in private practice: a long-term case series
      study.
AB  - BACKGROUND: Osseointegrated dental implants have become a routinely recommended
      procedure in the clinical practice of dentistry and periodontics. Due to their
      predictability, they have changed the way many cases are treatment planned. The
      purpose of this paper is to report the results of a prospective study of factors
      affecting the successes and failures of a large group of dental implants and
      compare them to published literature. METHODS: A total of 1,003 consecutively
      placed pure titanium dental implants placed from August 1987 to January 2002 and
      followed to October 2003 are reported. All implants were placed in one private
      practice by the same surgeon. RESULTS: Success rates statistically were
      influenced only by the age of the implant, although when the raw data are
      examined, some trends are seen. Success was unaffected by patient age, gender,
      surface roughness of implant, site of placement, smoking, bone type, arch, screw
      versus press-fit, diameter, length, manufacturer, reason for tooth loss, site
      bony augmentation and timing, placement timing, one-versus two-stage placement,
      or torque testing of implants; 75% of failures occurred before restoration.
      CONCLUSIONS: Osseointegrated dental implants are a highly predictable procedure
      with proper case selection. Failure rates vary for a number of factors reviewed,
      although only the age of the implant was statistically important in predicting
      failure. Male smokers, maxillary first molars, and type 4 bone had increased
      failure rates. Threaded, surface-roughened implants had the highest success
      rates.

PMID- 15974865
TI  - Telomeres and telomerase influence the course of human diseases, aging and
      carcinogenesis.

PMID- 15974866
TI  - In the end, it's all structure.
AB  - Chromosome end protection is essential for all organisms with linear genomes.
      Specialized structures, called telomeres, accomplish this protection by forming
      DNA-protein complexes that hide the natural chromosome ends from the DNA damage
      machinery. In mammalian cells protection takes place on several levels. Telomeric
      DNA forms large duplex loops with the help of telomeric proteins, consequently
      hiding the very tip of the telomere. Telomeric proteins play additional roles in
      protecting the end from degradation, regulating telomere length, and suppressing
      the DNA damage response machinery. Here we summarize the current knowledge about
      telomere structure, and discuss the future directions of the field.

PMID- 15974867
TI  - Telomere induced senescence: end game signaling.
AB  - The telomere-based model of cell aging has proven to among been among the most
      enduring hypotheses in cell biology. This model, suggesting that the gradual loss
      of telomere sequences during the proliferation of cultured human somatic cells
      imposes a barrier on cellular replicative potential, has been strongly supported
      by recent genetic and biochemical studies. In addition, evidence implicating
      telomere dynamics in organismal ageing and cancer progression in vivo suggest
      that such a process is likely to have considerable physiological relevance in
      homeostasis and disease. What is the sensing mechanism for shortened telomeres
      and what is the molecular basis for the ensuing checkpoint response? Moreover,
      what is the outcome when such failsafe mechanisms are lost? Here we will review
      the signaling pathways that are induced by alterations in telomere length and
      integrity and illustrate how these processes provoke downstream effects on cell
      proliferation and survival. In addition, we discuss how the telomere-induced
      pathways intersect with the DNA damage response and document how the failure in
      either process results in unrestrained chromosomal instability.

PMID- 15974868
TI  - Modeling premature aging syndromes with the telomerase knockout mouse.
AB  - Understanding the molecular basis of the aging process is a daunting problem,
      given the complex genetic and physiological changes that underlie human aging and
      the lack of genetically amenable primate model systems. However, analysis of
      mouse models exhibiting aging phenotypes reminiscent of those observed in elderly
      humans has enhanced our understanding of the biological mechanisms underlying
      mammalian aging. In particular, these mouse models have brought to light the
      importance of the DNA damage pathway during the aging process. Increased genomic
      instability is associated with accelerated cellular decline and manifestation of
      premature aging phenotypes in mice. Here I discuss how one form of genomic
      instability, initiated by critically short telomeres in the telomerase knockout
      mouse, perturb normal mammalian aging. Insights into the molecular pathways of
      the aging process may offer unprecedented opportunities to delay the deleterious
      effects of the aging process.

PMID- 15974869
TI  - Dyskeratosis congenita -- a disease of dysfunctional telomere maintenance.
AB  - Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome
      associated with abnormalities of the skin, fingernails, and tongue. Other
      clinical manifestations may include epiphora, lung fibrosis, liver cirrhosis,
      osteoporosis, and a predisposition to develop a variety of malignancies. The
      clinical picture often resembles that of a premature aging syndrome and tissues
      affected are those with a high cell turnover. DC has been linked to mutations in
      at least four distinct genes, three of which have been identified. The product of
      these genes, dyskerin, the telomerase RNA (TERC), and the catalytic unit of
      telomerase (TERT) are part of a ribonucleoprotein complex, the telomerase enzyme,
      that is essential for the elongation and maintenance of chromosome ends or
      telomeres. All patients with DC have excessively short telomeres, indicating that
      the underlying defect in these individuals is an inability to maintain the
      telomeres. The purpose of the current review is to highlight recent insights into
      the molecular pathogenesis of DC. We discuss the impact these findings have on
      our current understanding of telomere function and maintenance, and on the
      diagnosis, management, and treatment of patients with conditions caused by
      dysfunctional telomeres.

PMID- 15974870
TI  - Skin aging: a role for telomerase and telomere dynamics?
AB  - Skin is a complex tissue composed of two very different compartments -- the
      continuously renewing epidermis made up mostly by keratinocytes and the
      underlying matrix-rich dermis with the resting fibroblasts as its major cellular
      components. Both compartments are tightly interconnected and a paracrine mutual
      interaction is essential for epidermal growth, differentiation, and tissue
      homeostasis. Skin aging is commonly viewed as wrinkle formation, hair greying,
      and impaired wound healing. Nevertheless, the epidermis as the outermost shield
      needs to remain intact in order to guarantee an inside-out and outside-in barrier
      function throughout life time of a human being. Furthermore, the epidermis is one
      of the few regenerative tissues that express telomerase, the ribonucleoprotein
      complex that can counteract telomere erosion, one of the presently mostly
      favoured potential mechanisms causing cellular aging. This raises the question
      whether in the epidermis telomerase is able to counteract telomere erosion and
      thereby to prevents a telomere-dependent aging process and consequently which
      part of the skin is responsible for the most obvious changes associated with skin
      aging.

PMID- 15974871
TI  - Telomere dynamics in hematopoietic stem cells.
AB  - The hematopoietic system has an outstanding regenerative capacity which depends
      on a relatively small population of hematopoietic stem cells (HSC). In contrast
      to normal human cells, blood-forming stem cells, like most of their counterparts
      from other adult tissues, exhibit telomerase activity to a certain level.
      Nevertheless, this telomerase activity does not prevent telomere shortening in
      HSC, suggesting a restriction of their proliferative capacity. Here, we review
      recent studies on telomere dynamics in HSC of humans and mice. Furthermore, we
      discuss the impact of telomere manipulation in HSC for possible clinical
      applications and speculate on functions of telomerase beyond telomere
      lengthening.

PMID- 15974872
TI  - Telomere dynamics in response to chemotherapy.
AB  - The use of chemotherapy provides an essential arm in the treatment of a number of
      cancers. The biological feature common to all cancerous cells that sensitizes
      them to chemotherapeutic agents is their elevated division rate. Rapidly dividing
      cells, such as tumor cells, are more sensitive to chemotherapeutic agents that
      act to initiate pathways leading to cell death, a process enhanced in cells with
      compromised DNA damage responses. The toxicity accompanying chemotherapy is due
      to side-effects induced in normal regenerative tissues which also have relatively
      high replication rates, such as hair follicles, the hematopoietic system, the
      gastrointestinal system, the germline and skin cells. While the side-effects of
      chemotherapy may be tolerated by the patient, the long term impact of the
      cytotoxic effects of chemotherapy on healthy tissues is only now becoming
      apparent. Chemotherapy-induced cytotoxicity in regenerative tissues requires
      multiple cell divisions in order to reconstitute the affected tissues. At least
      in part as a consequence of these extra divisions, telomeres in individuals
      treated with chemotherapy are shorter than age-matched control individuals who
      have never been exposed to these drugs. Given the essential role of telomeres in
      regulating cellular aging and chromosomal stability, it is possible that the
      prematurely shortened telomeres that arise following chemotherapy may impact the
      long-term replicative potential of these tissues. This review is focused on how
      telomeres may be modulated, directly or indirectly, by anticancer drugs and the
      potential long-term consequences of accelerated telomere shortening in healthy
      tissue as a result of current cancer treatment protocols.

PMID- 15974873
TI  - Telomeres as biomarkers for ageing and age-related diseases.
AB  - Telomeres in telomerase-negative cells shorten during DNA replication in vitro
      due to numerous causes including the inability of DNA polymerases to fully copy
      the lagging strand, DNA end processing and random damage, often caused by
      oxidative stress. Short telomeres activate replicative senescence, an
      irreversible cell cycle arrest. Thus, telomere length is an indicator of
      replicative history, of the probability of cell senescence, and of the cumulative
      history of oxidative stress. Telomeres in most human cells shorten during ageing
      in vivo as well, suggesting that telomere length could be a biomarker of ageing
      and age-related morbidity. There are two distinct possibilities: First, in a
      tissue-specific fashion, short telomeres might indicate senescence of (stem)
      cells, and this might contribute to age-related functional attenuation in this
      tissue. Second, short telomeres in one tissue might cause systemic effects or
      might simply indicate a history of high stress and damage in the individual and
      could thus act as risk markers for age-related disease residing in a completely
      different tissue. In recent years, data have been published to support both
      approaches, and we will review these. While they together paint a fairly
      promising picture, it needs to be pointed out that until now most of the evidence
      is correlative, that much of it comes from underpowered studies, and that causal
      evidence for essential pathways, for instance for the impact of cell senescence
      on tissue ageing in vivo, is still very weak.

PMID- 15974874
TI  - Telomerase therapeutics for degenerative diseases.
AB  - Telomerase is active in early embryonic and fetal development but is down
      regulated in all human somatic tissues before birth. Since telomerase is
      virtually absent or only transiently active in normal somatic cells throughout
      postnatal life, telomere length gradually decreases as a function of age in most
      human tissues. Although telomerase repression likely evolved as a tumor
      suppressor mechanism, a growing body of evidence from epidemiology and genetic
      studies point to a role of telomerase repression and short telomeres in a broad
      spectrum of diseases: (a) Humans with shorter than average telomere length are at
      increased risk of dying from heart disease, stroke, or infection; (b) Patients
      with Dyskeratosis congenita are born with shortened telomeres due to mutations in
      telomerase components, suffer from a variety of proliferative tissue disorders,
      and typically die early of bone marrow failure; and (c) Individuals with long
      term chronic stress or infections have accelerated telomere shortening compared
      to age-matched counterparts. Telomerase activation may prove useful in the
      treatment of diseases associated with telomere loss. While human cells dividing
      in culture lose telomeric DNA and undergo changes that mirror certain age- or
      disease-associated changes in vivo, telomerase transduced cells have extended
      replicative capacities, increased resistance to stress, improved functional
      activities in vitro and in vivo, and no loss of differentiation capacity or
      growth control. In addition, telomerase transduction in vivo can prevent telomere
      dysfunction and cirrhotic changes in liver of telomerase knockout mice. Thus,
      pharmacological activation of telomerase has significant potential for the
      treatment of a broad spectrum of chronic or degenerative diseases.

PMID- 15974875
TI  - Telomeres, crisis and cancer.
AB  - Eukaryotic chromosomes terminate in specialized nucleic acid-protein complexes
      known as telomeres. Disruption of telomere structure by erosion of telomeric DNA
      or loss of telomere binding protein function activates a signal transduction
      program that closely resembles the cellular responses generated upon DNA damage.
      Telomere dysfunction in turn induces a permanent proliferation arrest known as
      senescence. Senescence is postulated to perform a tumor suppressor function by
      limiting cellular proliferative capacity, thus imposing a barrier to cellular
      immortalization. Genetic or epigenetic silencing of components of the DNA damage
      pathway, allows cells to proliferate beyond senescence limits. However, these
      cells eventually reach a stage of extreme telomere dysfunction known as crisis
      that is characterized by cell death and the concomitant appearance of cytogenetic
      abnormalities. Telomeric crisis produces significant chromosomal instability, a
      hallmark of human cancer, and may thus be relevant to carcinogenesis by
      increasing the occurrence of genetic alterations that would favor neoplastic
      transformation. The following review examines the relationship of telomere
      function during crisis in accelerating chromosomal instability and cancer.

PMID- 15974876
TI  - Telomeres, telomerase and malignant transformation.
AB  - Human cancer arises in a stepwise process by the accumulation of genetic
      alterations in oncogenes, tumor suppressor genes and other genes involved in the
      regulation of cell growth and proliferation. Many genes, important for the
      pathogenesis of various cancers and the pathways through which they act, have
      been characterized over the past decades. 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. In
      this context, immortalization is an essential prerequisite for the formation of a
      tumor cell. Besides classical cancer related pathways as the pRB and p53 tumor
      suppressor pathway or the ras signaling pathway, the maintenance of telomeres
      plays an essential role in both of these processes. Alterations in telomere
      biology both suppress and facilitate malignant transformation by regulating
      genomic stability and cellular life span. This review will summarize recent
      advances in the understanding of the molecular mechanisms of malignant
      transformation in human cells and the role of telomere maintenance in these
      processes. This ultimately leads to the development of cellular models of human
      cancer that phenocopy the corresponding disease. Furthermore, in the future these
      models could provide an ideal basis for the testing of novel chemopreventive or
      therapeutic approaches in the treatment of different types of human cancer.

PMID- 15974877
TI  - Telomere and telomerase dynamics in human cells.
AB  - Accumulating evidence now implicates telomeres and telomerase as critical
      regulators genomic stability and replicative lifespan in mammalian cells.
      Disruption of telomere maintenance and/or telomerase expression contributes to
      the etiology of some degenerative diseases and may participate in the process of
      aging. Although telomere dysfunction and aberrant telomerase expression clearly
      play important roles in cancer development, the contribution of telomere biology
      to cancer is complex and involves both positive and negative influences on tumor
      development. Indeed, recent work from several laboratories suggests additional
      roles for telomeres and telomerase in both normal and malignant physiology.
      Understanding the complexity of telomere biology will provide further insights
      into chromosome biology in both normal and malignant cells.

PMID- 15974878
TI  - Extratelomeric functions of telomerase.
AB  - Telomerase reverse transcriptase (TERT), a catalytic subunit of telomerase, has
      been demonstrated to exert a reverse transcriptase function when combined with
      telomerase RNA component (TERC), the complex of which ensures the maintenance of
      telomere length in all eukaryotes. Telomerase also prevents cell death, and
      promotes survival in many types of cells, from various tissues or organs
      including neurons, muscle, and immune cells, as well as a variety of tumor cells.
      Recently, a new aspect of telomerase activity, independent of telomere
      lengthening, has emerged to explain its protective effects on cell survival.
      Consistent with this, TERT was found to enhance tumorigenesis, and to regulate
      the expression of genes that control cell growth, which cannot be explained by
      telomere stabilization per se. Furthermore, the observation that TERT resides not
      only in the nucleus, but also in the cytosol, reinforces the notion of possible
      telomere-independent functions. In this review, recent studies regarding the
      extratelomeric functions of TERT have been comprehensively summarized, and their
      implications discussed.

PMID- 15974879
TI  - Telomerase-dependent gene therapy.
AB  - Adenovirus-mediated gene therapy approaches have evolved as promising means for
      cancer treatment during the last decade. Utilizing a broad spectrum of tumor
      specific promoters, numerous oncotropic vectors have been created with
      exceptional properties regarding tumor-restricted specificity. The discovery of
      telomerase, its high prevalence in tumor tissues and the discovery of its
      transcriptional regulation via the hTERT promoter have extended the applicability
      of adenoviral gene therapy vectors to approximately 90% of all tumors. First
      generation adenoviral vectors expressing transgenes under the control of the
      hTERT promoter confirmed the therapeutic potential but were restricted to
      initially transduced cancer cells. Recently, telomerase-dependent conditionally
      replicative adenoviral vectors (CRADs) have been developed that combine the
      specificity of hTERT promoter based expression systems with the lytic efficacy of
      replicative viruses. To evaluate the potential for clinical applications, various
      efforts have been made to establish combinative strategies including systemic
      chemotherapy, radiotherapy and antiangiogenesis. This review highlights the rapid
      advances of telomerase-based gene therapy and gives insight into future prospects
      and future development of oncotropic vectors.

PMID- 15974880
TI  - Telomere maintenance and tumorigenesis: an "ALT"ernative road.
AB  - The acquisition of cellular immortality is a critical step in human
      tumorigenesis. While the vast majority of human tumors activate the catalytic
      component of telomerase (hTERT) to stabilize their telomeres and attain
      immortality, a significant portion (7-10%) utilize a poorly defined alternative
      form of telomere maintenance referred to as ALT. Interestingly, telomerase
      activation is often favored in tumors arising from the epithelial compartment
      whereas ALT occurs in a more significant portion of tumors that arise from
      tissues of mesenchymal origin. This observation raises the possibility that cell
      type specific mechanisms favor the activation of telomerase versus ALT in human
      tumorigenesis. Because cellular immortality is critical to tumorigenesis it may
      represent an important anti-neoplastic target. Indeed, several approaches have
      successfully eliminated telomerase activity in human tumor models and some of
      these approaches are now moving into clinical trials. While these results are
      encouraging, it is clear that these approaches will have no impact on cells that
      utilize the ALT mechanism for telomere maintenance. Furthermore, the existence of
      ALT raises the possibility that telomerase-positive tumors undergoing anti
      telomerase therapies may escape by activating the ALT pathway. For these reasons
      a detailed understanding of the ALT pathway is critical to the future design of
      anti-neoplastic therapies.

PMID- 15974881
TI  - Glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous mechanical
      intervention for acute myocardial infarction.
AB  - Limitations in study designs and adoption of rigid criteria for randomization in
      clinical trials on acute myocardial infarction (AMI) may result in the enrollment
      of artificial populations, and subsequent trial results may be misleading in many
      ways rendering problematic the generalization of the trial results to a "real
      world population" of AMI. Furthermore, the "frequentist" approach in study
      designs with inclusion of thousands of low-risk patients and high statistical
      inference have produced inconclusive or negative results despite the high
      potential for a strong impact on outcome of the study drug, or device, or
      strategy. The investigative approaches to the use of IIb/IIIa inhibitors as
      adjunctive treatment to primary coronary intervention (PCI) for AMI are a clear
      instance of this crucial problem in the evidence-based medicine era. Five
      concluded randomized trials comparing abciximab with placebo in patients
      undergoing primary PCI for AMI have produced different and conflicting results
      with a broad spectrum of possibilities. No benefit of the drug in patients
      receiving infarct artery stenting, benefit of the drug only in patients
      undergoing conventional balloon angioplasty with provisional stenting and limited
      to the early phase, and mainly driven by the decrease in the need for urgent
      target vessel revascularization, benefit in terms of decreased mortality,
      reinfarction and target vessel revascularization at 1-month but not maintained at
      6 months, long-term benefit in the composite of death, reinfarction and target
      vessel revascularization, improved early and late outcome including long-term
      survival. This review of the trials of abciximab and other IIb/IIIa inhibitors in
      patients undergoing PCI for AMI tries to put the studies and their results into a
      proper perspective for the correct use of adjunctive IIb/IIIa inhibitor use in
      patients with AMI.

PMID- 15974882
TI  - The pharmacologic approach to the prevention of preeclampsia: from antiplatelet,
      antithrombosis and antioxidant therapy to anticonvulsants.
AB  - Preeclampsia has been suggested to be a two-stage disorder of an alteration in
      placental perfusion (stage 1) leading to generalized vascular endothelial damage
      (stage 2). Because the mechanism linking the two stages remains unclear,
      effective primary prevention is still impossible. However, advances made in our
      understanding of the pathophysiology of preeclampsia have paved the way for
      secondary and tertiary prevention approaches. Platelets are known to be activated
      in early pregnancy. They also play a pivotal role in the process of inflammation,
      as demonstrated by the finding that CD40 ligand is shed from activated platelets
      to directly initiate inflammation of the vessel wall. According to the Cochrane
      Library Update summarizing data from over 30,000 women, secondary prevention with
      antiplatelet drugs is associated with a 19% decrease in the risk of preeclampsia.
      Additional randomized controlled trials are needed to establish the association
      between preeclampsia and thrombophilia. The effect of the antithrombotic agent
      heparin on pregnancy outcome in preeclampsia and its potential preventive action
      in high-risk patients need to be elucidated. One of the several hypotheses of the
      pathogenesis of preeclampsia focuses on the oxidative stress caused by the
      imbalance in prooxidant and antioxidant forces. Preliminary findings on vitamin E
      and vitamin C supplementation in preeclamptic women are encouraging, and suggest
      a rationale for larger clinical trials. Although there is currently no
      explanation for the positive effect of magnesium sulfate on eclamptic seizures,
      studies have provided enough evidence to encourage its worldwide use as the
      primary anticonvulsant of choice in the tertiary prevention of maternal and
      perinatal death in severe preeclampsia/eclampsia. In conclusion, secondary and
      tertiary prevention of preeclampsia is possible when targeted at reducing
      maternal and neonatal morbidity and mortality.

PMID- 15974883
TI  - Risk stratification of dyslipidemia: insights from the Framingham Study.
AB  - Dyslipidemia, fundamental to the atherosclerotic process, is now a readily
      correctable risk factor with established efficacy of treatment for reducing risk
      of CHD and strokes. The current focus on LDL-cholesterol for risk assessment
      needs to be broadened to accommodate the two-way traffic of cholesterol entering
      and leaving the arterial intima reflected by the LDL/HDL ratio or the Total/HDL
      ratio. The choice of lipid therapy should be individualized to take into account
      the presence of the metabolic syndrome and the lipid profile of the patient. The
      intensity of therapy and goals should be linked to multivariable risk,
      particularly in those with modest lipid values. Cardiovascular risk factor
      clustering is pronounced for each lipid, is promoted by adiposity and greatly
      influences its CHD hazard. Global risk assessment taking clustering into account
      is essential for efficient preventive management of lipids. More attention needs
      to be afforded the absolute risk reduction attainable and must recognize that the
      number needed to treat to prevent one event increases the lower the lipid value,
      the lower global risk and the healthier the subject.

PMID- 15974884
TI  - Pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors: candidate mechanisms for anti-lipid deposition in blood vessels.
AB  - The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are
      considered first-line therapeutic agents for the prevention of coronary heart
      disease and atherosclerotic disorders related to hypercholesterolemia. Statins
      inhibit lipid deposition in the aortic endothelium. Although it has been accepted
      that the statins are potent inhibitors of cholesterol biosynthesis in the liver
      and that they lower circulating cholesterol levels, several cholesterol
      independent (pleiotropic) effects have been reported. The cholesterol-independent
      effects of statins involve normalization of the nitric oxide (NO)-NO synthase
      system, anti-inflammatory effects through the inhibition of cytokine/chemokine
      production, inhibition of vascular smooth muscle cell proliferation and
      migration, and inhibition of platelet thrombus formation/reduction of the
      thrombotic response. Some pleiotropic effects of statins may depend on the
      inhibition of the biosynthesis of farnesyl- and geranylgeranyl-nonsterol
      compounds from mevalonate in the cells. The Rho/Rho kinase pathway and the
      phospatidylinositol-3 kinase/Akt pathway mediate the pleiotropic effects of
      statins. As variations occur in absorption, metabolism, and excretion mechanisms
      due to the characteristics of specific statins including their hydrophilicity and
      lipophilicity, there are differences in the transfer mechanisms of statins into
      tissues. However, the pleiotropic effects occur regardless of statin
      hydrophilicity and lipophilicity. This review summarizes the pleiotropic effects
      of statins on lipid deposition in blood vessels.

PMID- 15974885
TI  - Aspirin and clopidogrel: a sweeping combination in cardiology.
AB  - Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed
      to be integrally involved in both the development and progression of
      atherosclerotic heart disease, as well as in its acute thrombotic complications.
      Antiplatelet therapy constitutes the cornerstone in the management of patients
      with acute coronary syndromes and generally high-risk patients with
      atherothrombosis. Until recently, long-term antiplatelet therapy for the
      treatment and prevention of the complications of atherothrombotic disease was
      traditionally limited to aspirin. The availability of the thienopyridines, in
      particular clopidogrel, represents an important addition to the physician's
      armamentarium. Clopidogrel is currently one of the most widely prescribed drugs
      for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel
      interfere with platelet activation in complementary, but separate pathways.
      Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of
      thromboxane A(2), which is a prothrombotic and vasoconstrictive substance.
      Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due
      to a more favorable safety profile, irreversibly prevents platelet activation by
      blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the
      P2Y(12) receptor) on the platelet surface, thus interfering with platelet
      activation, degranulation and aggregation. Both these antiplatelet agents have a
      potent protective effect against adverse vascular events, but the combination of
      these two agents has an even stronger antiplatelet effect translating into
      superior antithrombotic protection in coronary, cerebral or peripheral arterial
      disease, without an inordinate increase in bleeding complications. A number of
      seminal clinical trials have demonstrated and confirmed the incremental benefit
      and efficacy of the combination of clopidogrel and aspirin therapy above and
      beyond that of aspirin alone, with multiple other important large-scale clinical
      trials currently ongoing. Newer data are being accumulated from studies where
      indications for the use of clopidogrel and aspirin continue to expand into other
      patient groups, rendering this dual antiplatelet drug therapy a sweeping
      combination in Cardiology. However, important issues remain to be further and
      more thoroughly explored about the benefit of this antiplatelet drug combination
      in these other patient groups, such as in patients with heart failure, where
      preliminary data indicate a favorable effect on thrombotic vascular events, in
      patients with atrial fibrillation, where there is hope that this combination may
      replace or be an alternative treatment modality to coumadin in certain
      subpopulations, in patients undergoing demanding catheter ablation procedures,
      where data point to a protective effect from thromboembolic events. Another
      pertaining issue to be further investigated is the occurrence of drug-resistance
      observed in some patients for both these antithrombotic agents. This article is a
      comprehensive review of all these data and the landmark trials on the two
      antiplatelet agents, the issues involved and the current recommendations for
      their use in patients with atherosclerotic heart disease and other cardiovascular
      disorders and procedures.

PMID- 15974886
TI  - Stent-based delivered anti-proliferative drugs in the prevention of coronary
      stent restenosis.
AB  - Coronary stents are currently used in most percutaneous coronary interventions,
      since they have demonstrated to reduce restenosis and allow to solve threatened
      closure after balloon angioplasty. Despite these beneficial effects, restenosis
      remains as the main limitation of percutaneous coronary interventions even with
      the use of coronary stents. In the last 3 years, some coronary stents eluting
      anti-proliferative drugs have demonstrated to dramatically reduce the risk of
      restenosis. By November 2004, two different types of antiproliferative drugs
      eluted by coronary stents are commercially available: sirolimus (rapamycin) and
      paclitaxel. The mechanisms, clinical evidence, as well as the remaining
      limitations of these drug-eluting stents are reviewed. The current knowledge of
      other anti-proliferative drugs that are currently under investigation is also
      reviewed.

PMID- 15974887
TI  - Cardiac adrenomedullin: its role in cardiac hypertrophy and heart failure.
AB  - Co-localization of adrenomedullin (AM) and its receptor components such as
      calcitonin receptor like receptor (CRLR), receptor activity modifying protein
      (RAMP)2 and RAMP3 in peripheral tissues, including the heart, kidney, and
      vasculature, suggests an important role for the peptide as a regulator of
      cardiovascular function. Indeed, we previously reported that AM gene expression
      and / or immunoreactivity are increased in the ventricles of cardiac hypertrophy
      and heart failure. Recently, we also found that not only levels of AM peptide and
      AM gene expression, but also mRNA levels of CRLR, RAMP2 and RAMP3 are increased
      in cardiac hypertrophy and failing heart. Cardiac myocytes and fibroblast produce
      and secrete two molecular forms of AM and express CRLR, RAMP2 and RAMP3, and AM
      is known to have inhibitory effect of collagen synthesis and antiproliferative
      effect in cardiac fibroblasts. Stimulation by IL-1beta significantly increased
      gene expression of AM and its receptor components in cardiac fibroblasts.
      Preincubated IL-1beta elevated the intracellular cAMP response to exogenous
      administered AM. AM antisense oligodeoxynucleotide treatment significantly
      lowered AM levels in cultured medium. IL-1beta significantly increased (3)H
      proline incorporation and AM antisense oligodeoxynucleotide treatment further
      increased (3)H-proline incorporation. Collectively, these results support a
      protective role for increased AM in the cardiac hypertrophy and heart failure.
      Then, we tested the effects of acute administration of AM in experimental and
      human heart failure, because AM has hemodynamic effects including vasodilation,
      increases in cardiac contractility, cardiac output, diuresis, and natriuresis. We
      observed profound and sustained cardiovascular, hormonal and renal effects. These
      effects may incorporate many of the therapeutic goals of heart failure
      management.

PMID- 15974888
TI  - Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated
      heart failure: a novel mechanism of drug-induced improvement in contractile
      performance of the failing heart.
AB  - Recent experimental and clinical observations indicate that over-expression of
      pro-inflammatory cytokines is actively implicated to chronic heart failure
      progression through their cytotoxic and negative inotropic effects. Calcium
      sensitizing agents, such as levosimendan, promotes inotropy by stabilizing
      troponin C in a configuration that enhances the calcium sensitivity of cardiac
      myofilaments, preserving also diastolic relaxation. Levosimendan also opens ATP
      dependent potassium channels in peripheral vessels, leading to vasodilatation.
      Large scale randomized clinical trials have shown that levosimendan
      administration in patients with severe heart failure due to left ventricular
      systolic dysfunction results in favorable hemodynamic changes, symptomatic
      benefit, and a reduction in short-term morbidity and mortality. This review
      describes current knowledge about novel cellular mechanisms associated with
      beneficial effects of levosimendan on cardiac contractile performance, focusing
      mainly on its immunomodulatory and anti-apoptotic properties. Levosimendan
      induced improvement in contractile reserve and clinical status of severe heart
      failure patients, seems to be related with the reduction of major pro
      inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling
      molecules Fas/Fas Ligand. Modulation of pro-inflammatory and pro-apoptotic
      pathways into the failing heart by levosimendan may be an additional
      pathophysiologic mechanism that prevents further clinical and hemodynamic
      consequences of abnormal immune responses in decompensated heart failure and
      beneficially affects the progression of the syndrome.

PMID- 15974889
TI  - Snake venom metalloproteinase containing a disintegrin-like domain, its structure
      activity relationships at interacting with integrins.
AB  - Snake venom disintegrins represent a family of RGD (Arg-Gly-Asp) or KGD (Lys-Gly
      Asp)-containing proteins which have been reported to be unique and potentially
      useful tools not only for investigating integrin-ligand interactions, but also
      for the development of anti-thrombotic agents in terms of their anti-platelet
      activities. Snake venom proteins containing a disintegrin-like domain represent
      another super-family of proteins in which many of them have been demonstrated to
      have similar ability to inhibit platelet aggregation and integrin-mediated cell
      adhesion as the disintegrins. This super-family includes a large number of snake
      venom metalloproteinases and disintegrin related, RGD-containing snake venom
      proteins (disintegrin-like proteins) such as dendroaspin. Recently, a family of
      homologues of the snake venom metalloproteinases have been found in a wide
      variety of mammalian tissues as well as in other eukaryotic organisms termed ADAM
      (a disintegrin-like and metalloproteinase) proteins. ADAMs are members of the
      metazincins that also include the related matrix metalloprotease (MMPs). Some of
      ADAM proteins have now shown to interact with integrins, and the disintegrin-like
      domain may be crucial part in their function as proteases. A description of
      structure-activity relationships of snake venom proteins containing a disintegrin
      like domain is outlined in this review, along with reports of the modulation of
      protein activity by recombinant mutation. Comparison is also made of the
      structural and functional features of the metalloproteinases in snakes compared
      with those from other species. The review is intended to provide insights in
      which may assist the development of new therapeutic approaches.

PMID- 15974890
TI  - Role of cardiovascular aldosterone in hypertension.
AB  - Aldosterone plays an important role in the pathogenesis of cardiovascular
      disease. We have reported that aldosterone is synthesized in cardiovascular
      tissues and local aldosterone synthesis plays important roles for hypertension
      and cardiac hypertrophy. High sodium intake develops and accelerates vascular
      injury and cardiac hypertrophy in SHRSP. Plasma aldosterone concentrations and
      PRA were decreased by high salt intake in SHRSP. Aldosterone production, the
      expression of CYP11B2 mRNA and angiotensin II receptor AT1R mRNA in blood vessels
      were significantly increased by high salt intake. These results suggest that high
      salt intake increases aldosterone production and expression of the AT1R mRNA in
      the vascular tissue in SHRSP, which may contribute to the development of
      malignant hypertension in salt-loaded SHRSP. However, there are several reports
      of conflicting data. Mineralocorticoid receptor (MR) binding is tightly regulated
      by the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which
      selectively metabolizes glucocorticoids to inactive metabolites, thus allowing
      for MR activation by aldosterone. We have reported that decreased 11beta-HSD2 in
      blood vessels in Dahl salt-sensitive (DS) rats, a model for salt-sensitive
      hypertension. Local aldosterone excess may play a significant role in the salt
      sensitivity and development of hypertension. High sodium intake decreased
      circulating rennin-angiotensin-aldosterone system and increased blood pressure
      and cardiac hypertrophy in DS rats, which were prevented by the treatment with a
      selective MR antagonist, eplerenone. Eplerenone also improved endothelial nitric
      oxide synthase (eNOS) activity and eNOS mRNA expression in blood vessels in DS
      rats. These results further suggest that not only circulating aldosterone but
      also local aldosterone is of critical importance in the pathophysiology of
      cardiovascular disorders.

PMID- 15974891
TI  - Influence of impaired liver methionine metabolism on the development of vascular
      disease and inflammation.
AB  - Methionine (Met) metabolism involves the sequential formation of S
      adenosylmethionine (SAM, the main biological methyl donor), S
      adenosylhomocysteine (SAH) and homocysteine (Hcy). Hcy can be remethylated to Met
      or catabolized through the trans-sulfuration pathway. In mammals, as much as 48%
      of Met metabolism and up to 85% of all transmethylation reactions occur in the
      liver. These figures underscore the central role played by this organ in Met
      metabolism. Maintaining the homeostasis of this metabolic cycle has proved to be
      essential for the preservation of liver function up to the point of preventing
      its neoplastic transformation. However, an adequate hepatic metabolism of Met is
      not only important for the liver parenchymal cell. Evidence has accumulated over
      the past few years supporting the involvement of Met-derived metabolites in the
      triggering or attenuation of pathological processes with systemic implications.
      This is best illustrated by the fact that a deteriorated liver function has
      emerged as a major factor in the development of hyperhomocysteinemia. Elevated
      plasma levels of Hcy have been related to several disorders including
      cardiovascular and cerebrovascular diseases. On the other end, liver damage also
      leads to deficient SAM synthesis. Among the consequences of impaired SAM
      synthesis in liver tissue are the enhanced production of pro-inflammatory
      cytokines and mediators. In this review, we will address the mechanisms and
      consequences of abnormal Met metabolism in liver injury, the systemic
      implications of such impairment and finally the potential therapeutic
      interventions.

PMID- 15974892
TI  - Editorial: advances in Alzheimer therapy: something old, something new, something
      borrowed, something blue.

PMID- 15974893
TI  - An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for
      the treatment of Alzheimer's disease.
AB  - Existing cholinesterase (ChE) inhibitor therapies for Alzheimer's disease (AD),
      while effective in improving cognitive, behavioral and functional impairments, do
      not alter disease progression. Novel drug design studies have focused on the
      classical ChE inhibitor, (-)-physostigmine, producing alterations in chemical
      composition and three-dimensional structure, which may offer an improved
      therapeutic index. The phenylcarbamate derivative, (-)-phenserine, is a
      selective, non-competitive inhibitor of acetylcholinesterase (AChE). In vivo, (-)
      phenserine produces rapid, potent, and long-lasting AChE inhibition. As a
      possible result of its preferential brain selectivity, (-)-phenserine is
      significantly less toxic than (-)-physostigmine. In studies using the Stone maze
      paradigm, (-)-phenserine has been shown to improve cognitive performance in both
      young learning-impaired and elderly rats. In addition to reducing inactivation of
      acetylcholine in the brain, (-)-phenserine appears to have a second mode of
      action. Reduced secretion of beta-amyloid (Abeta) has been observed in cell lines
      exposed to (-)-phenserine, occurring through translational regulation of beta
      amyloid precursor protein (beta-APP) mRNA via a non-cholinergic mechanism. These
      in vitro findings appear to translate in vivo into animal models and humans. In a
      small study of patients with AD, (-)-phenserine treatment tended to reduce beta
      APP and Abeta levels in plasma samples. Clinical studies also reveal that (-)
      phenserine (5-10 mg b.i.d.) had a favorable safety and pharmacological profile,
      produced significant improvements in cognitive function and was well tolerated in
      patients with AD treated for 12 weeks. Further randomized, double-blind, placebo
      controlled Phase III studies assessing the efficacy, safety/tolerability and
      potential disease-modifying effects of (-)-phenserine in patients with AD are
      currently ongoing.

PMID- 15974894
TI  - Memory deficits correlating with acetylcholinesterase splice shift and amyloid
      burden in doubly transgenic mice.
AB  - Current mouse models of Alzheimer's disease show brain pathology that correlates
      to a degree with memory impairment, but underlying molecular mechanisms remained
      unknown. Here we report studies with three lines of transgenic mice: animals that
      doubly express mutated human amyloid precursor protein (APPswe) and human
      acetylcholinesterase (hAChE); and animals transgenic for only the APPswe or the
      hAChE. Among these genotypes, variations were observed in expression of mRNA for
      presenilin-1, which was highest in singly transgenic hAChE mice, and the stress
      inducible form of AChE, which was elevated when both transgenes were present. At
      the age of nine months, both double and single transgenic mice displayed working
      memory impairment in a radial arm water maze. However, as compared with mice
      expressing amyloid alone, the double transgenic animals exhibited more numerous
      plaques and greater amyloid burden in brain (both by histochemistry and by ELISA
      of amyloid protein). Moreover, the amyloid burden in double transgenics was
      tightly correlated with memory impairment as measured by total maze errors (r2=
      0.78, p = .002). This correlation was markedly stronger than observed in mice
      with amyloid alone. These new findings support the notion of cholinergic-amyloid
      interrelationships and highlight the double transgenic mice as a promising
      alternative for testing Alzheimer's therapies.

PMID- 15974895
TI  - Acetylcholinesterase-amyloid-beta-peptide interaction: effect of Congo Red and
      the role of the Wnt pathway.
AB  - The cholinergic system impairment observed in Alzheimer's disease (AD) patients
      leads to the cognitive, global and behavioral dysfunction commonly associated
      with dementia. The only treatment for AD has been the use of inhibitors of
      acetylcholinesterase (AChE) (E.C. 3.1.1.7), which is one of the several proteins
      associated with amyloid plaque deposits. Recently, novel dual inhibitors of AChE
      have been developed that target both the active site of the enzyme as well as the
      peripheral anionic site (PAS). Such inhibitors prevent the aggregation of amyloid
      beta-peptide (Abeta) into Alzheimer's fibrils. The incorporation of AChE, as a
      "chaperone" into amyloid aggregates results in the modification of the
      biochemical properties of the enzyme, including: sensitivity to low pH,
      inhibition at high substrate concentration, and increases of the Abeta
      neurotoxicity. Congo Red dye stabilizes the Abeta monomer, is able to inhibit
      oligomerization, and inhibits the binding of AChE to Abeta. However no effect of
      Congo Red on the binding of AChE to the Abeta preformed fibrils was observed.
      These studies suggest that different interactions between Abeta soluble-AChE and
      Abeta fibrils-AChE take place during the association between them. Docking
      studies were performed to evaluate the binding of Congo Red to Abeta in order to
      identify putative binding sites in the Abeta monomer that might interact with
      AChE. The binding site involves a region between residues 12 and 16. Finally,
      recent studies are consistent with the idea that a attenuating beta-catenin loss
      of function of Wnt signaling components may play a role in the progression of
      neurodegenerative disease, such as AD, providing a connection between AChE-Abeta
      neurotoxicity and the Wnt signal transduction pathway.

PMID- 15974896
TI  - Cholinesterases: roles in the brain during health and disease.
AB  - The cholinergic hypothesis of decline in dementia, whereby deficits in learning,
      memory and behavior are caused, at least in part, by decreased levels of
      acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role
      for acetylcholinesterase (AChE) and its inhibition in this scheme has long been
      accepted, but findings from preclinical experiments and clinical trials have
      placed butyrylcholinesterase (BuChE) alongside AChE as an important contributor
      to the occurrence, symptoms, progression and responses to treatment in dementia.
      A number of new lines of evidence suggest that both cholinesterase inhibitors
      (ChEs) may have broader functions in the CNS than previously thought, which
      relate to both 'classical' esterase activities of the enzymes as well as non
      classical actions unrelated to their enzymatic function. Data suggest involvement
      of the ChEs in modulating glial activation, cerebral blood flow, the amyloid
      cascade, and tau phosphorylation. It has therefore been speculated that some
      actions of the ChEs could affect the underlying disease processes in Alzheimer's
      disease (AD), and that pharmacological manipulation with ChE inhibitors may
      affect long-term disease progression. Focusing on new findings relating to BuChE,
      we review recent evidence that has extended knowledge into the roles of ChEs in
      health, disease and aging.

PMID- 15974897
TI  - Lessons from Darwin: evolutionary biology's implications for Alzheimer's disease
      research and patient care.
AB  - What are the aims appropriate for a science of clinical pharmacology and clinical
      trials: to test drugs for efficacy and safety in the clinic, to establish the
      optimal effectiveness and safety of drugs in patient care or both? Current
      designs of clinical trials test drugs for efficacy and safety in clinical
      settings-they do not address the clinician's problems adequately. Clinical trials
      better address the effectiveness of drugs in patient care with analyses to
      determine drug effects for each individual in the trial. We use current standards
      and designs for clinical trails supplemented to control random error effects for
      the individuals in the trials. Test-retest standard error of measurement can
      control random error effects for individuals. This allows individual clinical
      courses to be plotted with known precision and certainty. For individuals in a
      clinical trial the clinical course of surrogate outcome variables can be
      associated with long-term health outcomes in followup to develop clinical
      decision rules. Clinical courses on surrogate outcome variables during patient
      care can be interpreted using these clinical decision rules. In this Age of the
      Internet, Computers and Handhelds, electronic records and interpretations of
      clinical examinations and tests can be a part of decision making for every
      patient. We conclude that practical methods are available for making clinical
      trials more informative for clinical practice. This modification replaces
      "unsystematic clinical judgments" with statistically characterized data and
      interpretations for individuals available as care is delivered in the doctor's
      office. An AD demonstration can be viewed at www.healthpragmatics.com.

PMID- 15974898
TI  - JLK inhibitors: isocoumarin compounds as putative probes to selectively target
      the gamma-secretase pathway.
AB  - Alzheimer's disease is characterized by the extracellular deposition of the
      amyloid beta-peptide that derives from its precursor betaAPP by sequential
      actions of beta- and gamma- secretases, respectively. Recent studies aimed at
      identifying these enzymes have been reported as it is thougth that their
      inhibition should hopefully lead to reduce Abeta load in the AD brains. beta
      secretase seems to be due to BACE1, a novel membrane-bound aspartyl protease.
      gamma-secretase identification is still a matter of controversy. Invalidation of
      presenilin genes was reported to impair both gamma-secretase-mediated Abeta
      production and Notch cleavage leading to NICD production. This observation
      together with another biochemical and pharmacological evidences led to suggest
      that presenilins could be the genuine long-searched gamma-secretase that would be
      responsible for both APP and Notch cleavages. We have designed novel non peptidic
      potential inhibitors of gamma-secretase (referred to as JLK inhibitors) and
      examined their ability to prevent Abeta40 and Abeta42 secretions as well as NICD
      production. Three out of a series of these agents drastically lower the
      recoveries of both Abeta40 and Abeta42 produced by betaAPP-expressing cell lines
      and concomitantly protect intracellular C99 and C83 recoveries. These inhibitors
      also prevent Abeta40/42 productions by C99-expressing cells. Interestingly, these
      inhibitors were totally unable to affect the DeltaENotch cleavage leading to NICD
      generation. Here, we also further characterize the pharmacological properties and
      specificity of these JLK inhibitors.

PMID- 15974899
TI  - Pharmacological approaches of neurofibrillary degeneration.
AB  - Alzheimer disease (AD) and related tauopathies are all characterized
      histopathologically by neurofibrillary degeneration. The neurofibrillary changes,
      whether of paired helical filaments (PHF), twisted ribbons or straight filaments
      (SF) are made up of abnormally hyperphosphorylated tau. Unlike normal tau which
      promotes assembly and maintains structure of microtubules, the abnormal tau not
      only lacks these functions but also sequesters normal tau, MAP1 and MAP2, and
      causes disassembly of microtubules. This toxic behavior of the abnormal tau is
      solely due to its hyperphosphorylation because dephosphorylation restores it into
      a normal-like protein. The abnormal hyperphosphorylation also promotes the self
      assembly of tau into PHF/SF. The state of phosphorylation of a phosphoprotein is
      the function of the activities of protein kinases and as well as of protein
      phosphatases that regulate the level of phosphorylation. A cause of the abnormal
      hyperphosphorylation in AD brain is a decrease in the activity of protein
      phosphatase (PP)-2A, a major regulator of the phosphorylation of tau. A decrease
      in PP-2A activity results in the abnormal hyperphosphorylation of tau not only by
      decreased dephosphorylation of tau but also by stimulating the activities of tau
      kinases like CaMKII, PKA and MAP kinases which are regulated by PP-2A. Thus, the
      abnormal hyperphosphorylation can be inhibited both by inhibition of the
      activity/s of a tau protein kinase and as well as by restoration of the
      activity/s of a tau protein phosphatase. The development of drugs that inhibit
      neurofibrillary degeneration is a very promising and feasible therapeutic
      approach to inhibit the progression of AD and related tauopathies.

PMID- 15974901
TI  - Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents
      in the treatment of neurodegenerative disease.
AB  - Inflammation is characteristic of a broad spectrum of neurodegenerative diseases.
      These include Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases,
      amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and
      many other less common conditions. Morphologically, the level of inflammation is
      determined by the concentration and degree of activation of microglial cells.
      Biochemically, it is judged by the presence of a spectrum of inflammatory
      mediators. Epidemiological evidence indicates that anti-inflammatory agents such
      as non-steroidal anti-inflammatory drugs (NSAIDs) have a sparing effect on AD and
      PD indicating that inflammation exacerbates the pathology in these diseases.
      NSAIDs are protective in transgenic animal models of AD, providing further
      evidence of the negative consequences of inflammation. Here we describe an in
      vitro model, which was used to study the protective effects of NSAIDs in AD. This
      model is based on neuronal cell killing by stimulated microglia or microglia-like
      cells. In this model NSAIDs show protective effects at a therapeutically relevant
      level, which is in the low micromolar range. There are reports suggesting that
      NSAIDs act independently of cyclooxygenase (COX) inhibition, but only at higher
      doses. Classical NSAIDs are still the most logical choice for agents that will
      slow the progression or delay the onset of AD and other neurodegenerative
      diseases despite failures of naproxen, celecoxib and rofecoxib in AD clinical
      trials. Several other classes of anti-inflammatory drugs have been identified as
      potentially beneficial in this and similar assay systems. Therefore combination
      therapy with other anti-inflammatory agents that work through different
      mechanisms of action might prove to be a superior therapeutic strategy.

PMID- 15974900
TI  - Atorvastatin therapy lowers circulating cholesterol but not free radical activity
      in advance of identifiable clinical benefit in the treatment of mild-to-moderate
      AD.
AB  - Cholesterol-induced production of amyloid beta (Abeta) as a putative neurotoxin
      in Alzheimer's disease (AD), along with epidemiological evidence, suggests that
      statin drugs may provide benefit in treatment of the disorder. We tested the
      effect of once daily atorvastatin calcium (80 mg; two 40 mg tablets) on cognitive
      and/or behavioral decline in patients with mild-to-moderate AD. The study was
      designed as a pilot intention-to-treat, proof-of-concept, double-blind, placebo
      controlled, randomized (1:1) trial with a 1-year exposure to study medication
      employing last-observation-carried-forward (LOCF) ANCOVA as the primary
      statistical method of assessment. Alternate statistical methods were employed to
      further explore the effect of atorvastatin treatment on progression of
      deterioration. Of the 98 individuals with mild-to-moderate AD (Mini-Mental State
      Examination score of 12-28) providing Informed Consent, 71 were eligible for
      randomization, 67 were randomized and 63 completed the 3-month visit and were
      statistically evaluable. The primary outcome measures were change in the
      Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) performance and the
      Clinical Global Impression of Change (CGIC). Secondary outcome measures included
      the MMSE, Geriatric Depression Scale (GDS), the Neuropsychiatric Inventory (NPI)
      and the ADCS Activities of Daily Living inventory (ADCS-ADL). Tertiary outcome
      measures included levels of total circulating cholesterol, LDL and VLDL, and
      circulating activity of the free radical scavenger enzymes superoxide dismutase
      (SOD) and glutathione peroxidase (GpX). Atorvastatin reduced circulating
      cholesterol levels and produced a positive signal on each of the clinical outcome
      measures compared to placebo, but did not elicit a difference in circulating SOD
      or GpX activities. The observed beneficial clinical effect reached significance
      for the GDS (p = 0.040) and the ADAS-cog at 6 months (p = 0.003), was all but
      significant for the ADAS-cog (p = 0.055) at 12 months, and was of marginal
      significance for the CGIC (p = 0.073) and NPI (p = 0.071) at 12 months when
      employing the primary statistical approach (ANCOVA with LOCF). Application of
      repeated measures ANCOVA statistics revealed the difference was significant for
      the CGIC and marginally significant for the ADAS-cog, but not significant for the
      other clinical indices. This evaluation indicated significant time-by-treatment
      interactions (altered progression) for the ADAS-cog and MMSE, but not the CGIC.
      Application of random intercept regression analysis revealed a significant
      difference for the CGIC, ADAS-cog and MMSE. Regression analysis also indicated
      that atorvastatin produced change in the slope of deterioration on the MMSE.
      Accordingly, atorvastatin therapy may be an effective treatment and may slow the
      progression of AD among mild-to-moderately affected patients.

PMID- 15974902
TI  - Possible use of autologous stem cell therapies for Alzheimer's disease.
AB  - The statement, "neurodegenerative diseases are incurable because neurons do not
      regenerate during adulthood," has been challenged, and we have now found much
      evidence that the matured brain is capable of regenerating neurons. In our
      previous study, human neural stem cells (HNSCs) transplanted into aged rat brains
      differentiated into neural cells and significantly improved the cognitive
      functions of the animals, indicating that HNSCs may be a promising candidate for
      neuro-replacement therapy. However, because of ethical and practical issues
      associated with HNSCs, development of autologous stem cell strategies may be
      desired. We established new technologies to differentiate adult human mesenchymal
      stem cells into neural cells by modifying cell fate decisions. We also found a
      pyrimidine derivative that increases endogenous stem cell proliferation and
      neurogenesis after peripheral administrations of this compound. Although these
      results may promise a bright future for clinical applications of stem cell
      strategies in Alzheimer's disease (AD) therapy, we must acknowledge the
      complexity of AD. For example, abnormal metabolism of the amyloid-beta precursor
      protein (APP) may affect stem cell biology, while the prevalence of amyloid-beta
      peptide (Abeta) toxicity theory in AD pathology tends to limit our focus on the
      physiological functions of APP. We found that excess APP in the environment
      causes glial differentiation of stem cells. Even though the glial activation may
      be useful to eliminate Abeta deposits, neuronal differentiation of stem cells is
      needed for replacement of degenerating neurons in the AD brain. Thus, further
      investigation of the influence of AD pathology on stem cell biology is required.

PMID- 15974903
TI  - Enhancing central nervous system endogenous GLP-1 receptor pathways for
      intervention in Alzheimer's disease.
AB  - Glucagon-like peptide-1 (7-36)--amide (GLP-1) is an endogenous insulinotropic
      peptide that is secreted from the gastrointestinal tract in response to food. It
      enhances pancreatic islet beta-cell proliferation, glucose-dependent insulin
      secretion, and lowers blood glucose and food intake in patients with type 2
      diabetes mellitus. GLP-1 receptors, are coupled to the cyclic AMP second
      messenger pathway, and are expressed throughout the brain of rodents and humans.
      We previously reported that GLP-1 and exendin-4, a naturally occurring, long
      acting analogue of GLP-1 that binds the GLP-1 receptor (GLP-1R), possess
      neurotrophic properties. GLP-1R agonists protect neurons against amyloid-beta
      peptide (Abeta) and glutamate-induced apoptosis in cell culture studies and
      attenuate cholinergic neuron atrophy in the basal forebrain of the rat following
      an excitotoxic lesion. The biochemical cascades activated by neural GLP-1R
      stimulation are discussed in comparison to those activated by pancreatic
      receptors, and, additionally, are compared to signaling pathways associated with
      the classical neurotrophins. GLP-1R stimulation promotes pathways that favour
      cell survival over apoptosis. GLP-1 readily enters brain, and its diverse
      physiological actions, which include insulinotropic, cardiovascular as well as
      neurotrophic ones, may prove beneficial in a variety of diseases prevalent in
      aging, including Alzheimer's disease (AD). Its ability to lower brain levels of
      Abeta in mice would appear to be particularly pertinent in this regard.
      Furthermore, the ready availability of clinical material and the clinical history
      of its long term use in subjects with type 2 diabetes would support testing the
      value of GLP-1R agonists in AD trials.

PMID- 15974904
TI  - Advancing drug discovery for Alzheimer's disease.

PMID- 15974905
TI  - Development of novel amyloid imaging agents based upon thioflavin S.
AB  - To date, small-molecule amyloid-imaging agents for in vivo detection and
      quantitation of amyloid deposits in Alzheimer's disease (AD) have been developed
      and successfully applied to human subjects. Preliminary studies have indicated
      that these amyloid-imaging agents were accumulated in the AD brains in a pattern
      that is relatively consistent with AD pathology, at least in the regions of
      amyloid-rich grey matter. These studies have also proven the concept that amyloid
      dyes, normally too hydrophilic to enter the brain, can be chemically modified to
      enhance brain permeability, binding affinity, as well as improve binding
      specificity for amyloid deposits. Related studies have suggested that
      structurally different agents can be developed that bind to different sites on
      amyloid deposits. In fact, in vivo cross-referencing studies based upon different
      amyloid-imaging agents may permit better characterization of AD pathology. But
      more importantly, novel amyloid imaging agents are required that will allow
      direct correlation between the results of animal models and human subjects based
      upon identical imaging modalities. Thus far, amyloid stains such as Congo red and
      thioflavin T have been extensively studied. However, another widely used amyloid
      dye, thioflavin S, has not been previously explored. This is in part due to the
      fact that thioflavin S exists as a mixture, not a pure chemical entity, albeit
      that the major component has been characterized. We hypothesized that neutral
      analogs, based upon the major component, could be developed as novel amyloid
      imaging agents, that exhibit complementary binding properties and pharmacokinetic
      profiles compatible with potential human studies.

PMID- 15974906
TI  - Functional connectivity in elderly controls and AD patients using resting state
      fMRI: a pilot study.
AB  - Conventionally, Alzheimer's disease (AD) and other dementias are diagnosed using
      clinical assessment, neuropsychology and also structural neuroimaging, showing
      neuronal degeneration starting in the hippocampal regions. However, there is an
      increasing need for a new method that is more sensitive to early AD
      identification than currently possible. A new promising technique that may be
      used for this is to measure local brain activation using functional magnetic
      resonance imaging (fMRI), since functional loss predates structural loss of brain
      tissue. A new method to apply fMRI is to study connectivity between brain regions
      during a resting state without application of a task. Recent data suggest that
      connectivity within memory systems during such a resting state is associated with
      the level of memory function. Here we explain how we will study healthy elderly
      controls, patients with a mild cognitive impairment (MCI, considered to be a
      transitional stage between normal condition and AD), and AD patients using
      resting state connectivity fMRI. If resting state connectivity is sensitive to
      cognitive decline, this will be of great importance for noninvasive dementia
      research, offering a tool to easily study functional networks in the brain
      without the requirement of a memory task, and perhaps offering a tool sensitive
      for early diagnostics.

PMID- 15974907
TI  - Towards practical cognitive assessment for detection of early dementia: a 30
      minute computerized battery discriminates as well as longer testing.
AB  - Early detection of cognitive decline may lead to more effective treatment.
      Clinical cognitive assessment is essential for early detection, but must be brief
      with easily interpretable results. The present study defines and evaluates a 30
      minute cognitive battery consisting of a subset of tests that comprise a longer
      computerized battery recently validated in detecting mild cognitive impairment
      (MCI). Participants were from three tertiary care memory clinics and an assisted
      living facility (final group: N=161) with consensus diagnoses of cognitively
      healthy, MCI, or mild dementia. A comprehensive NeuroTrax battery evaluated
      memory, executive function, visual spatial perception, verbal function,
      information processing speed, and motor skills. Validity of a single summary
      measure ('MCI Score') designed for dementia detection and built exclusively from
      tests of memory, executive function, and visual spatial perception was evaluated
      with receiver operating characteristic (ROC) analysis. Discriminant validity
      (area under the curve: AUC) was at least as large for the 6-parameter MCI Score
      as for a 20-parameter score necessitating administration of the entire battery.
      Further, the MCI Score had a larger AUC with reduced variance relative to its
      constituent parameters. AUC for distinguishing dementia was 0.886; AUC for
      distinguishing cognitively healthy was 0.823. Finally, the MCI Score
      discriminated among all three diagnostic groups (ANOVA; F[2,150]=52.54, p<0.001).
      Hence a reduced NeuroTrax battery (30 minutes) with MCI Score is a useful
      clinical tool for summarizing cognitive data relevant to early dementia
      detection.

PMID- 15974908
TI  - C-1073 (mifepristone) in the adjunctive treatment of Alzheimer's disease.
AB  - Alzheimer's disease is frequently associated with abnormalities in the
      hypothalamic pituitary adrenal axis. Elevated cortisol levels in Alzheimer's
      disease may in turn be associated with a more rapid progression of the illness.
      In addition, elevated cortisol levels may directly contribute to cognitive
      deficits in Alzheimer's disease. Mifepristone is a potent antagonist of the
      glucocorticoid receptor and blocks the central actions of cortisol. The purpose
      of this study is to determine the effects of glucocorticoid receptor blockade
      with mifepristone on cognition in Alzheimer's disease.

PMID- 15974909
TI  - A potential role of the curry spice curcumin in Alzheimer's disease.
AB  - There is substantial in-vitro data indicating that curcumin has antioxidant, anti
      inflammatory, and anti-amyloid activity. In addition, studies in animal models of
      Alzheimer's disease (AD) indicate a direct effect of curcumin in decreasing the
      amyloid pathology of AD. As the widespread use of curcumin as a food additive and
      relatively small short-term studies in humans suggest safety, curcumin is a
      promising agent in the treatment and/or prevention of AD. Nonetheless, important
      information regarding curcumin bioavailability, safety and tolerability,
      particularly in an elderly population is lacking. We are therefore performing a
      study of curcumin in patients with AD to gather this information in addition to
      data on the effect of curcumin on biomarkers of AD pathology.

PMID- 15974910
TI  - Synaptic fatigue is more pronounced in the APP/PS1 transgenic mouse model of
      Alzheimer's disease.
AB  - To search for potential mechanism that might alter synaptic transmission
      following Abeta increase we have examined the presynaptic component of
      transmitter release. As parameters of synaptic transmission that might underlie
      presynaptic mechanisms, we have used paired-pulse facilitation (PPF), post
      tetanic potentiation (PTP), and synaptic fatigue (SF) at the connection between
      the hippocampal Schaffer-collateral pathway and CA1 pyramidal neurons in
      approximately 5 month old double transgenic mice overexpressing the mutated form
      of amyloid precursor protein (APPK670N, M671L) and presenilin 1 (PS1M146V). While
      the presynaptic mechanisms of PPF and PTP were not compromised in the APP/PS1
      mice, SF was more pronounced in the double transgenic animals. The percentage of
      the 40th fEPSP slope over the first during the tetanus was 18 -/+ 3% in APP/PS1
      vs. 26 -/+ 2% in WT. Thus, it is likely that presynaptic mechanisms underlying SF
      but not PPF and PTP, may account for synaptic dysfunction in APP/PS1 mice.

PMID- 15974911
TI  - Functional central nicotinic acetylcholine receptor antagonism by systemic
      administration of Tinuvin 770 (BTMPS).
AB  - Tinuvin 770 (BTMPS) is a non-competitive, use-dependent antagonist of nicotinic
      acetylcholine receptors (nAChRs). The drug is highly lipid soluble and as such it
      has the potential to act within the brain. Presently the ganglionic blocking drug
      mecamylamine is used almost exclusively to block central nAChRs upon peripheral
      administration. These experiments were designed to confirm the nAChR antagonism
      effectiveness of BTMPS in both peripheral (ganglionic stimulation) and central
      (locomotor activity and thermal nociceptive sensitivity) nicotinic system in
      vivo. BTMPS inhibited the expression of the pressor response produced by i.v.
      injection of the ganglionic stimulant DMPP in anesthetized rats. The inhibition
      dose-response profile appeared to be biphasic with the maximal inhibition
      occurring after administration of the 0.48 mg/kg dose of BTMPS. In rats
      acclimated to the test apparatus, nicotine increased different measures of
      locomotor activity, particularly at the 0.75 mg/kg dose. BTMPS pretreatment
      significantly inhibited the nicotine-induced increase in motor behaviors, again
      with a biphasic dose-response relationship. Lastly, nicotine elicited an
      antinociceptive response in rats (hot plate test). BTMPS almost completely
      blocked the antinociceptive responses to 1 and 1.5 mg/kg nicotine. On its own,
      BTMPS failed to decrease blood pressure and to decrease the nociceptive
      threshold. The drug also generally failed to alter locomotor activity. The use
      dependent aspect of BTMPS-induced inhibition of nAChRs was evident in the drug's
      greater effectiveness in the presence of the highest doses of nicotine.
      Therefore, BTMPS can be considered as an alternative to or as a confirmatory drug
      for mecamylamine when inhibition of central nicotinic receptors is required.

PMID- 15974912
TI  - The expression of activity-dependent neuroprotective protein (ADNP) is regulated
      by brain damage and treatment of mice with the ADNP derived peptide, NAP, reduces
      the severity of traumatic head injury.
AB  - NAP is a short octapeptide sequence (single letter code, NAPVSIPQ) that protects
      neurons against a wide variety of insults. The NAP sequence was identified by
      peptide structure/function scanning of activity-dependent neuroprotective protein
      (ADNP), a gene product essential for brain formation. To further evaluate the in
      vivo efficacy of NAP neuroprotection we used a mouse model of head trauma; a
      condition that presents a risk factor for the development of Alzheimer's disease
      in injured patients. In the mouse model, NAP treatment (prophylactic or curative)
      indicated improvement in longitudinal clinical, biochemical and anatomical
      outcomes. Furthermore, closed head injury was associated with a delayed increase
      in the expression of the immune cell surface glycoprotein Mac-1 (CD11B antigen)
      at the injury site that was decreased in NAP-treated mice. Additional experiments
      with Mac-1-deficient mice suggested partial protection against death related to
      severe head injury. NAP protection in Mac-1-deficient mice against adverse
      clinical outcome was concomitant with the time period when increases in Mac-1
      transcripts were observed in the Mac-1 expressing mice ( approximately four weeks
      after the injury). The expression of ADNP (the NAP parent protein) was also
      increased at the injured brain site four weeks after the traumatic event, only in
      Mac-1 expressing mice. Here, using immunocytochemistry, we localized the increase
      in ADNP to microglia and astrocyte-like cells. The increase in ADNP in injured
      brains is now suggested to be a part of an endogenous compensatory mechanism and
      NAP treatment provides an additional protection. Toxicology studies suggest NAP
      as safe for further clinical development.

PMID- 15974913
TI  - The molecular basis of memantine action in Alzheimer's disease and other
      neurologic disorders: low-affinity, uncompetitive antagonism.
AB  - In western countries, Alzheimer's disease (AD) is the most common form of
      dementia. In fact, if left uncurbed, the economic cost of caring for AD patients
      could consume the entire gross national product of the USA by the middle of this
      century. Until recently, the only available drugs for this condition were
      cholinergic treatments, which symptomatically enhance cognitive state to some
      degree, but they were not neuroprotective. In fact, many potential
      neuroprotective drugs tested in clinical trials failed because they were poorly
      tolerated. However, after our discovery of its clinically-tolerated mechanism of
      action, one neuroprotective drug, memantine, was recently approved by the
      European Union and the U.S. Food and Drug Administration (FDA) for the treatment
      of Alzheimer's disease. Recent phase 3 clinical trials have shown that memantine
      is effective in the treatment of both mild and moderate-to-severe Alzheimer's
      disease and possibly vascular dementia (multi-infarct dementia). Here we review
      the molecular mechanism of memantine's action and also the basis for the drug's
      use in these neurological diseases, which are mediated at least in part by
      excitotoxicity. Excitotoxicity is defined as excessive exposure to the
      neurotransmitter glutamate or overstimulation of its membrane receptors, leading
      to neuronal injury or death. Excitotoxic neuronal cell death is mediated in part
      by overactivation of N-methyl-d-aspartate (NMDA)-type glutamate receptors, which
      results in excessive Ca2+ influx through the receptor's associated ion channel.
      Physiological NMDA receptor activity, however, is also essential for normal
      neuronal function. This means that potential neuroprotective agents that block
      virtually all NMDA receptor activity will very likely have unacceptable clinical
      side effects. For this reason many previous NMDA receptor antagonists have
      disappointingly failed advanced clinical trials for a number of neurodegenerative
      disorders. In contrast, studies in our laboratory have shown that the adamantane
      derivative, memantine, preferentially blocks excessive NMDA receptor activity
      without disrupting normal activity. Memantine does this through its action as an
      uncompetitive, low-affinity, open-channel blocker; it enters the receptor
      associated ion channel preferentially when it is excessively open, and, most
      importantly, its off-rate is relatively fast so that it does not substantially
      accumulate in the channel to interfere with normal synaptic transmission.
      Clinical use has corroborated the prediction that memantine is thus well
      tolerated. Besides Alzheimer's disease, memantine is currently in trials for
      additional neurological disorders, including other forms of dementia, depression,
      glaucoma, and severe neuropathic pain. A series of second-generation memantine
      derivatives are currently in development and may prove to have even greater
      neuroprotective properties than memantine. These second-generation drugs take
      advantage of the fact that the NMDA receptor has other modulatory sites in
      addition to its ion channel that potentially could also be used for safe but
      effective clinical intervention.

PMID- 15974914
TI  - Neurotrophin receptor-based strategies for Alzheimer's disease.
AB  - The traditional perspective of applying neurotrophins in the context of
      Alzheimer's disease is based on the premise that neurotrophins are capable of
      upregulating cholinergic function and of rendering neurons less vulnerable to
      certain processes causing degeneration. Factors limiting the therapeutic
      application of neurotrophin proteins include their poor pharmacological
      properties and their pleiotropic effects mediated by interaction with Trk, p75NTR
      and sortilin receptors. Recent studies suggesting and that pro-forms of
      neurotrophins accumulating in Alzheimer's and other pathological states cause
      cell death, that p75NTR modulates amyloid beta- and injury-induced
      neurodegeneration and that small molecules can be created that bind specifically
      to individual neurotrophin receptors point to novel strategies by which
      neurotrophin receptors might be targeted in Alzheimer's and other
      neuropathological states.

PMID- 15974915
TI  - Nitric oxide mimetic molecules as therapeutic agents in Alzheimer's disease.
AB  - Nitric oxide is multifunctional messenger molecule in the brain, playing
      important roles including in learning and memory and in regulating the expression
      of trophic factors that may be reduced with aging. Small molecules that mimic the
      biological activity of NO, NO mimetics, will bypass cholinergic receptor
      activation and are anticipated to provide multiple pathways of treating and
      circumventing dementia in Alzheimer's disease. Activation of soluble guanylyl
      cyclase and cGMP formation in the brain represents one element of effective
      neuroprotective pathways mediated by NO. Substantial evidence suggests that NO
      mimetics may display cGMP-dependent and cGMP-independent activity and may operate
      via multiple biochemical signaling pathways, both to ensure the survival of
      neurons subjected to stress and also to provide cognition-enabling pathways to
      circumvent dementia. GT 1061 is an NO mimetic compound currently in clinical
      trials for Alzheimer's. A survey of current research indicates that NO mimetics
      will provide a combined neuroprotective and cognition-enabling approach to anti
      neurodegenerative therapy.

PMID- 15974917
TI  - Role of fractalkine (CX3CL1) in regulating neuron-microglia interactions:
      development of viral-based CX3CR1 antagonists.
AB  - Blocking the effects of fractalkine therapeutically may regulate microglia cell
      activation and provide neuroprotection in the AD brain. A human herpesvirus 8
      encoded chemokine, termed vMIP-II is a non-selective chemokine receptor
      antagonist (binding multiple chemokine receptors, including CX3CR1). By comparing
      vMIP-II and FKN, we have generated molecules that selectively antagonize CX3CR1
      activation. The results from these studies will guide future development of
      therapeutic agents designed to modulate microglial activation with the goal of
      preventing or slowing the progression of AD.

PMID- 15974916
TI  - Small molecule tgf-beta mimetics as potential neuroprotective factors.
AB  - Neurodegenerative and dementing illnesses are becoming an increasing social and
      economical burden as the number of older people continues to grow in
      industrialized countries. Current knowledge of the processes leading to these
      diseases is still limited, and very few effective treatments are available.
      Because neurodegeneration is associated with an activation of injury and innate
      immune responses in the brain, drugs that could mimic the beneficial aspects of
      this response are potential therapeutic candidates. The cytokine transforming
      growth factor (TGF)-beta1 is an organizer of the brain's response to injury and
      is known to be neuroprotective. Previous studies from our lab also showed that
      TGF-beta1 can reduce accumulation of beta-amyloid peptide (Abeta), which appears
      to be central to Alzheimer's disease (AD) pathogenesis, and we therefore
      initiated a search for small molecule chemical compounds that could mimic this
      effect. We report here the identification of several such TGF-beta mimetics
      detected in an in vitro screen of a library with 5000 chemically diverse
      compounds. If active in vivo, these mimetics could be developed into candidates
      for the treatment of neurodegeneration.

PMID- 15974918
TI  - Extracellular superoxide dismutase (EC-SOD) quenches free radicals and attenuates
      age-related cognitive decline: opportunities for novel drug development in aging.
AB  - Superoxide dismutase (SOD) is one of the most effective mechanisms in physiology
      for inactivating reactive oxygen species. Elevated SOD activity can be
      therapeutically useful by protecting against oxidative stress-induced
      neurotoxicity. Acutely increased extracellular-SOD (EC-SOD) activity protects
      against neurobehavioral impairment caused by acute ischemia. Chronically
      increased EC-SOD activity may also be therapeutically useful by protecting
      against chronic oxidative stress-induced neurobehavioral damage that accumulates
      during the aging process. We have found that mice with genetic overexpression of
      EC-SOD do not show the aging-induced decline in learning and memory that control,
      wild type mice show. From 14-22 months of age, the EC-SOD overexpressing mice
      have significantly better spatial learning working memory function than that of
      controls. This effect is specific to the aging period. Young adult EC-SOD
      overexpressing mice do not have better learning and memory function than
      controls. The beneficial effects of increased EC-SOD activity with aging may be
      achieved without risk of impairment during younger ages by chronically
      administering EC-SOD mimetics from mature adulthood into the aging period. Novel
      EC-SOD mimetics may be useful in attenuating aging-induced cognitive impairments
      and other aspects of physiological decline with aging.

PMID- 15974919
TI  - Validation of the neuroinflammation cycle as a drug discovery target using
      integrative chemical biology and lead compound development with an Alzheimer's
      disease-related mouse model.
AB  - The neuroinflammation cycle has been proposed as a potential therapeutic target
      in the development of new approaches to altering Alzheimer's disease (AD)
      progression. However, the efficacy and toxicological profile of compounds that
      focus only on classical NSAID targets have been disappointing to date. Therefore,
      we recently initiated an unbiased, integrative chemical biology approach that
      used a hierarchal set of cell-based screens, followed by efficacy analysis in a
      new AD-relevant animal model that more closely resembles human pathology
      endpoints in terms of neuroinflammation and neuronal loss. The prior
      investigations provided a proof of concept that targeting the neuroinflammation
      cycle may be a viable drug discovery approach for AD. However, recent informatics
      analyses of the high attrition rate in drug development have identified the need
      for starting drug development with lead compounds that are well below cut off
      values in computed molecular properties in order to facilitate late stage
      medicinal chemistry refinement to improve in vivo functions. We describe here how
      we are leveraging our novel, unbiased, integrative chemical biology approach for
      the rapid discovery of potential lead compounds for AD drug discovery.
      Specifically, we show that orally bioavailable compounds with the desired
      physical properties and in vivo functions can be identified in focused synthetic
      libraries composed of chemical diversifications of the inactive but privileged
      pyridazine molecular fragment.

PMID- 15974920
TI  - Analysis of genetic polymorphisms in acetylcholinesterase as reflected in
      different populations.
AB  - Acetylcholinesterase (AChE) plays a crucial physiological role in termination of
      impulse transmission at cholinergic synapses through rapid hydrolysis of
      acetylcholine. In addition, it was implicated in amyloid plaque formation, a
      hallmark of Alzheimer's disease (AD), and most of the drugs used in AD treatment
      are AChE inhibitors. Thus ACHE is an obvious candidate gene for pharmacogenetic
      study of AD treatment. However, AChE is a highly conserved molecule, and only a
      few naturally occurring genetic polymorphisms have been reported in the human
      gene. The goals of this study were to make a systematic effort to identify
      natural single nucleotide polymorphisms (SNPs) in the human ACHE gene, and to
      reveal their population specific architecture. To this end, the genomic coding
      sequences for AChE of 96 unrelated control individuals from three distinct ethnic
      groups, African Americans, Ashkenazi Jews and Israeli Arabs, were analyzed.
      Thirteen ACHE SNPs were identified, ten of which are newly described, and five of
      which should produce amino-acid substitutions (Arg34Gln, Gly57Arg, Glu344Gly,
      His353Asn and Pro592Arg). Population frequencies of 11 of the 13 SNPs were
      established in four different populations, African Americans, Ashkenazi Jews,
      Sephardic Jews and Israeli Arabs; 17 haplotypes and 5 ethno-specific alleles were
      identified, and a cladogram of ACHE haplotypes was constructed. Among the SNPs
      resulting in an amino-acid substitution, three are within the mature protein,
      mapping on its external surface; they are thus unlikely to affect its catalytic
      properties, yet could have antigenic consequences or affect putative protein
      protein interactions. Furthermore, the newly identified SNPs open the door to a
      study of the possible association of AChE with deleterious phenotypes - such as
      adverse drug responses to AChE inhibitors employed in treatment of AD patients
      and hypersensitivity to pesticides.

PMID- 15974921
TI  - Screening for inhibitors of tau polymerization.
AB  - The histopathological diagnosis of Alzheimer's disease relies on two kinds of
      proteinaceous aggregates: the extracellular plaques built from filaments of the
      Abeta-peptide and the intracellular tangles consisting of tau polymerized into
      Paired Helical Filaments (PHFs). The order of aggregation events is still under
      debate, but it is well accepted that tau-related changes have an important impact
      on the viability of neurons. In neurons, early morphological changes are seen in
      axons which begin to loose and retract synapses. This process is accompanied by
      an increase of aggregated tau protein. Thus the prevention of tau aggregation
      seems to be a valuable target for therapy of Alzheimer's disease. Here we present
      a screening procedure by which we identified inhibitors of tau polymerization. In
      the primary screen we used a thioflavin-S based assay which detects PHF formation
      in solution. These initial hits were further analyzed for their capacity to
      depolymerize preformed PHFs. These results were confirmed by several secondary
      assays (tryptophan fluorescence, pelleting, filter trapping and electron
      microscopy). By this approach it is possible to identify small molecule compounds
      which prevent or reverse the aggregation of tau and thereby might improve the
      viability of neurons in a therapeutic approach.

PMID- 15974922
TI  - Cytoskeletal integrity as a drug target.
AB  - The cytoskeleton provides structural integrity and determines localization of
      proteins and organelles throughout the cell. The focus on structure and transport
      has overshadowed the role this ubiquitous network plays in cell signaling
      cascades, though it participates in transduction of signals from the plasma
      membrane to the nucleus. Clearly the discovery that neurofibrillary tangles
      (NFTs) in Alzheimer's disease (AD) brain are made up of the microtubule (MT)
      associated protein tau and evidence that the toxic amyloid peptides in AD can
      lead to tau hyper-phosphorylation and cytoskeletal dystrophy support the
      assertion that disruption of the MT network is an early signaling event in
      neurodegenerative cascades. Thus we have been testing the hypothesis that drugs
      that can moderate such signals through interactions with MTs would protect
      neurons against Abeta toxicity. Drugs targeted to MTs are currently used as anti
      cancer agents, due to their blockade of cell proliferation and induction of cell
      death. However, we and others have now found that low concentrations of compounds
      that help stabilize MTs do indeed protect post-mitotic neurons challenged with
      various toxic stimuli. Therefore we propose that the cytoskeletal network
      actually serves as a sensor for the overall state of the neurons and a first-line
      transducer of stress signals. Drugs that can moderate initiation of such early
      signaling events do protect against disruption of the cytoskeleton and neuritic
      dystrophy in neuronal cell cultures. In vivo proof-of-concept studies in animal
      models will require the development of agents that can protect cytoskeletal
      integrity and also cross the blood brain barrier.

PMID- 15974923
TI  - Development of a high throughput drug screening assay for the detection of
      changes in tau levels -- proof of concept with HSP90 inhibitors.
AB  - Therapeutic development for Alzheimer's disease has largely focused on the
      removal of beta amyloid because of its suggested role in the primary agent in
      initiating the disease process. However, with the recent discovery of mutations
      that result as pathologic buildup of tau in the absence of amyloid pathology, tau
      is beginning to be recognized as a potential target for drug discovery. We have
      developed a high-throughput drug screening method that allows for direct
      intracellular quantitation of tau protein species, enabling the fast, reliable
      detection of these changes. We have identified a family of small, blood brain
      barrier penetrant heat shock protein 90 inhibitors that significantly reduce tau
      protein levels in vitro. Western blot analysis demonstrated a clear inverse
      correlation between the tau levels and the increase in HSP27, HSP40 and HSP90.
      Modifications to this assay will further allow the specific analysis of
      pathologically relevant species. Using this assay, we have demonstrated that a
      class of HSP90 inhibitors is able to significantly lower intracellular tau levels
      most likely through induction of a heat shock response.

PMID- 15974924
TI  - Lentiviral vector-based models of amyloid pathology: from cells to animals.
AB  - Lentiviral vectors are efficient tools for the introduction of genes into a wide
      range of established and primary cells in vitro, ex vivo, and in vivo, and also
      permit efficient transgenesis in a wide range of mammalian species. Our goals
      have been to apply the broad capabilities of the lentiviral vector system to AD
      research. Using a set of vectors expressing APP and PS1 genes, we demonstrated
      the efficiency and fidelity of the system for in vitro biochemical analyses of
      genes and pathways involved in plaque deposition. These analyses were performed
      in cell lines and in primary neuronal cultures, which have previously been
      difficult to use. The methods and tools described here are applicable to the
      study of effects of other genes and gene combinations on APP processing,
      including suppression of gene activity by delivering shRNAs. We have attempted to
      create local plaque pathology by stereotactic injection of APP and PS1 expressing
      vectors into mouse brains for use as a rapid model for plaque pathology that can
      be used in a broad range of mammals. No amyloid or preamyloid pathology has been
      detected over a six-month period; the possible reasons are discussed. Lastly, we
      have used the vectors to create transgenic rats expressing mutant APP and mutant
      PS1 and have obtained the first set of positive pups with more expected. The
      results presented here demonstrate the utility of Lentiviral vector-based
      approaches to the study of AD and other neurodegenerative diseases.

PMID- 15974925
TI  - Pilot study of the reducing effect on amyloidosis in vivo by three FDA pre
      approved drugs via the Alzheimer's APP 5' untranslated region.
AB  - A pilot study was conducted employing a well known mouse model for Alzheimer's
      disease to evaluate the anti-amyloid efficacy of three FDA pre-approved drugs.
      Paroxetine (SSRI and APP 5'UTR directed lead compound), N-acetyl cysteine
      (antioxidant), and erythromycin (macrolide antibiotic) were provided to the
      drinking water of TgCRND8 mice for three months. This report provides data that
      measured the steady-state levels of amyloid Abeta-40 and Abeta-42 Abeta as pmol
      Abeta per gram of mouse brain cortex in drug treated and placebo animals. The
      relative levels of Abeta peptide levels were reduced after exposure of mice to
      paroxetine (N=5), NAC (N=7), and erythromycin (N=7) relative to matched placebo
      counterparts. These results demonstrated proof-of concept for a strategy to
      further screen the APP 5'UTR target to identify novel drugs that exhibit anti
      amyloid efficacy in vivo. These data also demonstrated a statistically
      significant anti-amyloid trend for paroxetine, NAC and erythromycin. The
      potential for conducting further studies with these compounds using larger
      cohorts of TgCRND8 mice is discussed.

PMID- 15974926
TI  - Drug library screen to identify compounds that decrease secreted Abeta from a
      human cell line.
AB  - In order to discover compounds that may be useful in the prevention of Alzheimer
      disease, a drug library was screened for drugs that could decrease amyloid beta
      peptide (Abeta) accumulation secreted from a human CNS-derived cell line. Of the
      2160 compounds subjected to a primary screen, 16, or 0.74%, reduced Abeta
      accumulation by at least 40%. Seven of these compounds were confirmed to be
      effective in a secondary screen using each compound at a dose of 5 microM. Three
      of these seven compounds were more effective than the others at reducing Abeta
      levels in a tertiary screen, and led to 68 to 85% reductions in total Abeta, at
      the 25 microM dosage. The effects of these three drugs on secreted Abeta40,
      Abeta42, and sAPPalpha were also determined. Thus, we have identified lead
      compounds that may be useful for subsequent studies to determine the mechanism of
      action of each drug, as well as for pre-clinical studies to determine whether
      each of these drugs is safe and effective in vivo.

PMID- 15974927
TI  - Recent developments on the studies of human memapsin 2 (beta-secretase).
AB  - Several specific topics on recent findings in the studies of memapsin 2 (beta
      secretase) are discussed in this article. New structural evidence on memapsin 2
      has pointed to the structural basis of flap opening. Such a mechanism is thought
      to participate in the substrate sequence selection during the cellular function.
      Another potentially important area is the intracellular transport of memapsin 2.
      Here we discuss the involvement of APP in memapsin 2 endocytosis and the GGA
      proteins in recycling the protease back to the cell surface. These mechanisms may
      be connected with the cellular regulation of neuronal activity through the
      regulation of memapsin 2 activity and Abeta production.

PMID- 15974928
TI  - An Abeta sequestration approach using non-antibody Abeta binding agents.
AB  - Amyloid beta (Abeta) has been considered as a primary cause of Alzheimer's
      disease (AD), and Abeta lowering approaches have been tested. Active immunization
      against Abeta is one of several promising Abeta-lowering approaches. Two
      mechanisms have been proposed: enhancement of microglial phagocytosis and Abeta
      sequestration (also called "peripheral sink"). We hypothesized that Abeta
      sequestration without immune modulation is sufficient to reduce the brain Abeta
      load and have demonstrated effective sequestration with Abeta binding agents that
      do not stimulate an immune reaction. Recent reports from other groups showed two
      other non-immune related Abeta binding agents, which have no structural relation
      to compounds we previously tested, reduced brain Abeta after peripheral
      administration. Congo red is a chemically synthesized small molecule that has
      binding affinity to Abeta. In the present study, we tested three Congo red
      derivatives in Abeta plaque-forming mice at an early pathological stage.
      Unfortunately, peripheral administration for three weeks did not substantially
      alter brain Abeta load. Optimized Abeta binding agents with high affinity to
      soluble Abeta are necessary for the sequestration approach.

PMID- 15974929
TI  - LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP.
AB  - The pathogenesis of Alzheimer's disease (AD) involves the abnormal accumulation
      and deposition of beta-amyloid in cerebral blood vessels and in the brain
      parenchyma. Critical in modulating beta-amyloid deposition in brain is the flux
      of Abeta across the blood brain barrier. The low-density lipoprotein receptor
      related protein (LRP), is a large endocytic receptor that mediates the efflux of
      Abeta out of brain and into the periphery. The first step in the LRP-mediated
      clearance of Abeta involves the formation of a complex between Abeta and the LRP
      ligands apolipoprotein E (apoE) or alpha(2)-macroglobulin (alpha(2)M). The
      Abeta/chaperone complexes then bind to LRP via binding sites on apoE or
      alpha(2)M. The efflux of Abeta/chaperone complexes out of the neuropil and into
      the periphery may be attenuated by LRP-ligands that compete with apoE or
      alpha(2)M for LRP binding. LRP is also the cell surface receptor for Kunitz
      Protease Inhibitor (KPI) containing isoforms of Abeta's parent protein, the
      amyloid protein precursor (APP). Protein and mRNA levels of KPI-containing APP
      isoforms (APP-KPI) are elevated in AD brain and are associated with increased
      Abeta production. In this study we show that soluble non-amyloidogenic APP-KPI
      can also inhibit the uptake of Abeta/alpha(2)M in a cell culture model of LRP
      mediated Abeta clearance. Clearance of Abeta/apoE complexes was not inhibited by
      APP-KPI. Our findings are consistent with studies showing that apoE and alpha(2)M
      have discrete binding sites on LRP. Most significantly, our data suggests that
      the elevated levels of APP-KPI in AD brain may attenuate the clearance of Abeta,
      the proteins own amyloidogenic catabolic product.

PMID- 15974931
TI  - Allosterism at muscarinic receptors: ligands and mechanisms.
AB  - The evaluation of allosteric ligands at muscarinic receptors is discussed in
      terms of the ability of the experimental data to be interpreted by the allosteric
      ternary complex model. The compilation of useful SAR information of allosteric
      ligands is not simple, especially for muscarinic receptors, where there are
      multiple allosteric sites and complex interactions.

PMID- 15974932
TI  - Allosteric modulation of the adenosine family of receptors.
AB  - Allosteric modulators for adenosine receptors (ARs) are of an increasing interest
      and may have potential therapeutic advantage over orthosteric ligands.
      Benzoylthiophene derivatives (including PD 81,723), 2-aminothiazolium salts, and
      related allosteric modulators of the A(1) AR have been studied. The
      benzoylthiophene derivatives were demonstrated to be selective enhancers for the
      A(1) AR, with little or no effect on other subtypes of ARs. Allosteric modulation
      of the A(2A) AR has also been reported. A(3) allosteric enhancers may be
      predicted to be useful against ischemic conditions. We have recently
      characterized two classes of A(3) AR allosteric modulators: 3-(2
      pyridinyl)isoquinolines (e.g. VUF5455) and 1H-imidazo-[4,5-c]quinolin-4-amines
      (e.g. DU124183), which selectively decreased the agonist dissociation rate at the
      human A(3)AR but not at A(1) and A(2A) ARs. DU124183 left-shifted the agonist
      conc.-response curve for inhibition of forskolin-stimulated cAMP accumulation in
      intact cells expressing the human A(3)AR with up to 30% potentiation of the
      maximal efficacy. The increased potency of A(3) agonists was evident only in the
      presence of an A(3) antagonist, since VUF5455 and DU124183 also antagonized, i.e.
      displaced binding at the orthosteric site, with K(i) values of 1.68 and 0.82
      microM, respectively. A(3)AR mutagenesis studies implicated F182(5.43) and
      N274(7.45) in the action of the enhancers and was interpreted using a rhodopsin
      based A(3)AR molecular model, suggesting multiple binding modes. Amiloride
      analogues, SCH-202676 (N-(2,3-diphenyl-1,2,4-thiadiazol-5(2H)
      ylidene)methanamine), and sodium ions were demonstrated to be common allosteric
      modulators for at least three subtypes (A(1), A(2A), and A(3)) of ARs.

PMID- 15974933
TI  - Allosteric modulation of dopamine receptors.
AB  - Allosteric modulators allow for the fine-tuning of receptor responses to
      endogenous neurotransmitters and exogenous therapeutic agents. Different types of
      allosteric modulation of dopamine receptors are discussed as well as the
      significance of such modulation in the control of normal biological processes and
      in the treatment of disease.

PMID- 15974934
TI  - A review on quantitative structure-activity relationships (QSARs) of natural and
      synthetic antioxidants compounds.
AB  - During the last decade an increasing number of reports describe the roles of
      active oxygen species in the development or exacerbation of various kinds of
      diseases. Antioxidants are of great interest because of their involvement in
      important biological and industrial processes. They have been found to possess
      anticancer, anti-cardiovascular, anti-inflammatory and many other activities.
      Many attempts have been made to elucidate the QSAR of antioxidants by using
      different physicochemical parameters. Unfortunately the limited number of
      antioxidants and the unavailable sigma Hammett values of complex substituents did
      not lead to significant results in regression analysis. The redox potentials are
      well correlated to the antioxidant activities. In this report we will attempt to
      collect and discuss all the published results concerning the QSAR research on
      natural and synthetic antioxidants compounds.

PMID- 15974935
TI  - Inhibitors of membrane receptors involved with leukocyte extravasation.
AB  - The migration of leukocytes from the blood stream to sites of infection is a key
      event in cellular immune response, mediated by multiple types of molecules
      including several adhesion receptors. The inhibition of adhesion receptors holds
      great promise for novel therapeutical strategies to treat chronic inflammatory
      disorders or autoimmune diseases. This review reports on recent advances in
      adhesion-based therapeutics and focuses on structural classification of selectin
      and integrin inhibitors.

PMID- 15974936
TI  - Structure-activity relationships for the design of small-molecule inhibitors.
AB  - One of the most important stages of the drug discovery process is the generation
      of lead compounds. Structure-activity relationships (SAR) are well-integrated in
      modern drug discovery and have been largely used for the finding of new leads,
      scaffold generation, the optimization of receptor or enzyme affinity, as well as
      of pharmacokinetic and physicochemical properties. This review highlights some
      SAR approaches that can be used to optimize leads through a continuous, multi
      step process based on knowledge gained at each stage, thus exploiting SAR in the
      design of selective, potent, small-molecule drug candidates.

PMID- 15974937
TI  - Recent advances in neuromuscular blocking agents.
AB  - Since the introduction of (+)-tubocurarine into anaesthetic and surgical practice
      (1942), a number of non-depolarizing neuromuscular blocking agents (NMBs) with
      improved pharmacological properties have been developed during the last sixty
      years. However, after withdrawal of rapacuronium from clinical use, there is
      still a need for an ultra-short acting non-depolarizing muscle relaxant with
      rapid onset as substitution for the polarizing suxamethonium, which has several
      undesirable side-effects. In this paper, structure-activity relationships within
      four different series of NMBs (tetrahydroisoquinolinium, bistropinyl diester,
      aminosteroid, and amino peptide analogues) published in this millennium have been
      reviewed. The NMB properties of the most promising drug candidates from each
      series were discussed and compared to those of the already existing muscle
      relaxants.

PMID- 15974938
TI  - Benefits, problems and alternatives to COX-2 inhibition.

PMID- 15974939
TI  - COX-2 selective inhibitors in the treatment of arthritis: a rheumatologist
      perspective.
AB  - COX-2 selective inhibitors were developed in order to provide similar efficacy to
      traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) but with
      improved upper gastrointestinal safety. This paper presents an overview of
      randomized clinical trials demonstrating the efficacy of COX-2 selective
      inhibitors for the treatment of patients with arthritis, particularly
      osteoarthritis and rheumatoid arthritis. In osteoarthritis and rheumatoid
      arthritis, COX-2 selective inhibitors have been shown to be more effective than
      placebo and similarly effective as standard doses of nonselective NSAIDs. There
      are currently few randomized clinical trials comparing the efficacy of the 2
      first-generation COX-2 selective inhibitors, celecoxib and rofecoxib, in
      osteoarthritis. Of 4 head-to-head studies comparing the 2 agents, 3 indicated
      similar efficacy, while the other demonstrated superiority of rofecoxib at a dose
      of 25 mg qd compared with celecoxib at a dose of 200 mg qd. There are no clinical
      trials comparing the efficacy of different agents for treatment of patients with
      rheumatoid arthritis. Some studies have also demonstrated efficacy for COX-2
      selective inhibitors in patients with ankylosing spondylitis and gout. In
      aggregate, these data show that COX-2 selective inhibitors provide effective
      relief of pain in patients with osteoarthritis and rheumatoid arthritis, with
      efficacy that is similar to traditional NSAIDs. Cost-effectiveness and cost
      utility studies suggest, however, that their use should be limited to patients at
      high risk of serious upper gastrointestinal side effects, including complicated
      ulcers.

PMID- 15974940
TI  - Impact of COX-2 inhibitors in common clinical practice a gastroenterologist's
      perspective.
AB  - Non-selective NSAIDs enhance the risk of serious ulcer complications (bleeding,
      perforation, obstruction), hospitalization and death about 3-10-fold. The
      gastrointestinal side effects of NSAIDs have a considerable economical burden,
      since they are responsible for 5-10 billion dollars in hospitalization charges
      and lost work time. NSAIDs cause gastrointestinal damage by both topical and
      systemic effects. COX-1-mediated inhibition of prostaglandin synthesis is
      probably the most relevant mechanism, but NSAIDs can cause gastrointestinal
      injury also by COX-independent pathways. COX-2-selective inhibitors (Coxibs) such
      as celecoxib, rofecoxib or valdecoxib have been developed to achieve an equal
      relief of pain and inflammation as classical NSAIDs but without their risk of
      gastrointestinal side effects. Within the first three months, celecoxib became
      the fastest selling drug in history. The gastrointestinal safety of classical
      NSAIDs and Coxibs has been compared in a variety of endoscopic investigations,
      meta-analyses and outcome studies. In conclusion, these studies have clearly
      shown, that Coxibs are associated with significantly less dyspeptic symptoms,
      erosions, ulcers and ulcer complications. In contrast, Coxibs seem to delay
      gastric ulcer healing to the same extent as traditional NSAIDs. Besides their
      effects on the upper gastrointestinal tract, NSAIDs can cause small intestinal
      inflammation, ulcers of the small and large intestine, ileal dysfunction,
      intestinal strictures, colitis and NSAID enteropathy. In addition, NSAIDs
      increase the risk of lower gastrointestinal complications including bleeding,
      perforation and obstruction. Current data suggest, that Coxibs are associated
      with a significantly lower risk of serious lower GI events than traditional
      NSAIDs. It is now under debate, who should receive COX-2-selective inhibitors
      instead of classical NSAIDs, since Coxibs are much more expensive. Data from cost
      effectiveness studies suggest, that Coxibs should currently be used only in
      patients with high risks of GI complications.

PMID- 15974941
TI  - Global safety of coxibs and NSAIDs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2
      inhibitors (Coxibs) are commonly used for minor pain treatment and chronically in
      the management of rheumatoid arthritis and osteoarthritis. Three areas of safety
      concerns are shared by both groups of drugs: Gastrointestinal complications
      (upper gastrointestinal bleeding, perforations or obstruction), cardiovascular
      safety (mainly myocardial infarction) and renal safety (acute renal failure,
      hypertension and electrolyte abnormalities). The incidence of renal complications
      may be increased two-fold with NSAIDs or coxibs, and there is no evidence for a
      major difference between the two groups of drugs. Coxibs are clearly associated
      with improved gastrointestinal safety compared to NSAIDs, but this benefit is
      reduced and may be lost completely with concurrent low-dose aspirin use. In
      contrast, coxibs may be associated with a greater incidence of cardiovascular
      complications, mainly myocardial infarction, especially in comparison to certain
      NSAIDs such as naproxen. Thus, coxibs are not generally safer than NSAIDs.
      Rather, their long-term use should be customized to individual patients and their
      intrinsic baseline risks and other medications required in their management.

PMID- 15974942
TI  - COX inhibition and NSAID-induced gastric damage--roles in various pathogenic
      events.
AB  - This article reviews our recent studies on NSAID-induced gastric damage, focusing
      on the relation between COX inhibition and pathogenic events. Conventional NSAIDs
      such as indomethacin, at a dose that inhibits PG production, enhance gastric
      motility, resulting in an increase in mucosal permeability and MPO activity, and
      eventually, gastric lesions. The development of these lesions can be prevented by
      administering PGE2 or antisecretory drugs, and also via an atropine-sensitive
      mechanism, not related to any antisecretory action. The selective COX-2 inhibitor
      rofecoxib has no effect on PG production and does not induce damage in the
      stomach. The selective COX-1 inhibitor SC-560 also does not cause damage, despite
      evoking a decrease in the PGE2 level. The combined administration of SC-560 and
      rofecoxib, however, provokes the formation of gastric lesions. SC-560, but not
      rofecoxib, causes gastric hypermotility and an increase in mucosal permeability,
      although the level of MPO activity increases only when rofecoxib is co
      administered. COX-2 mRNA is expressed in the stomach after administration of SC
      560 and indomethacin but not rofecoxib. The up-regulation of COX-2 expression in
      response to indomethacin is prevented by atropine at a dose that inhibits gastric
      hypermotility but not by omeprazole at an antisecretory dose. We conclude that
      the gastric ulcerogenic properties of NSAIDs are not accounted for solely by the
      inhibition of COX-1 and require the inhibition of both COX-1 and COX-2, the
      inhibition of COX-1 up-regulates COX-2 expression in association with gastric
      hypermotility, and PGs produced by COX-2 counteract the deleterious influences of
      the COX-1 inhibition.

PMID- 15974943
TI  - Dual COX-inhibitors: the answer is NO?
AB  - Nitric oxide (NO) releasing non-steroidal anti-inflammatory drugs (NSAIDs) are a
      new class of anti-inflammatory agents obtained by adding an NO releasing moiety
      to existing NSAIDs. They have also christened as COX inhibiting NO-donating drugs
      (CINOD). Preclinical and clinical studies suggest that CINOD inhibit COX-1 and
      COX-2 activities while cause less adverse effects on gastrointestinal tract in
      comparison to conventional NSAIDs and coxibs and reduce systemic blood pressure.
      A different class of NO-donating drugs has been obtained by coupling NO to
      aspirin. These NO-releasing aspirins are new chemical entities that maintain and
      possibly expands the pharmacological properties of aspirin, but spare the
      gastrointestinal mucosa. Animal studies have shown that CINOD and NO-aspirins
      maintain gastric mucosal blood flow and reduce leukocyte-endothelial cell
      adherence.

PMID- 15974944
TI  - Low dose aspirin, COX-inhibition and chemoprevention of colorectal cancer.
AB  - Chemoprevention of colorectal cancer involves the long-term use of pharmacologic
      agents that can prevent neoplasms from developing in the large bowel. This new
      approach requires major funding and human investments. Among the most widely
      studied agents for the chemoprevention of colorectal cancer, aspirin, the NSAIDs
      and COX-2 inhibitors seem to be the most promising. A large number of
      observational epidemiological studies show that regular use of aspirin and other
      NSAIDs is associated with a reduction in the risk of developing both colorectal
      adenomas and cancer. In addition, the prodrug sulindac reduces the growth of
      existing polyps in familial adenomatous polyposis (FAP). However, the dose,
      duration of effect and length of protection seen after cessation remain to be
      fully established. Furthermore, in view of previous discrepancies between the
      results of observational studies and randomized control trials (RCTs), it is
      crucially important to investigate the effects of aspirin by RCTs. RCTs
      investigating the effect of chemopreventive agents on adenoma recurrence as an
      intermediate endpoint for colorectal cancer is a more feasible approach than RCTs
      to investigate the effect on the incidence if colorectal cancer per se. Four RCTs
      of the effect of aspirin on adenoma recurrence are available. Other trials are
      currently underway.

PMID- 15974945
TI  - Mechanisms of colon cancer prevention with and beyond COX-2 inhibition.
AB  - Colorectal cancer is the most common cancer in Western countries and the second
      leading cause of cancer-related death. Sporadic lesions represent 75-80% of all
      colorectal cancer, whereas 20-25% are in younger individuals or in patients with
      a family history of cancer, suggesting a heritable susceptibility. Persons with
      germline alterations in cancer-promoting genes, such as those with familial
      adenomatous polyposis and hereditary non-polyposis colorectal cancer, stand to
      benefit significantly from chemopreventive interventions, along with those who
      had already developed any colorectal neoplasia (either adenoma or carcinoma).
      Among the most promising approaches to chemoprevention is the use of non
      steroidal anti-inflammatory drugs, including both selective and non-selective
      cyclooxigenase-2 inhibitors. Although the present article is mainly focused on
      these drugs and their mechanisms of action, other strategies with potential
      involvement in colorectal cancer chemoprevention such as peroxisome proliferator
      activated receptor ligands, epithelial growth factor receptor blockers, calcium,
      vitamin D, folate, and DNA methyltransferase inhibitors are also reviewed.

PMID- 15974946
TI  - Chemoprevention of colorectal cancer: ready for routine use?
AB  - In the third millennium preventive medicine is becoming a corner stone in our
      concept of health. Colorectal cancer (CRC) prevention, in particular, has become
      an important goal for health providers, physicians and the general public. CRC
      fits the criteria of a disease suitable for chemopreventive interventions. It is
      a prevalent disease that is associated with considerable mortality and morbidity
      rates, with more than 1,000,000 new cases and 500,000 deaths expected, worldwide,
      in 2004. CRC has a natural history of transition from precursor to malignant
      lesion that spans, on average, 15-20 years, providing a window of opportunity for
      effective interventions and prevention. A pre-malignant precursor lesion (i.e.,
      adenoma) usually precedes cancer, and helps to identify a subset of the
      population that is at increased risk of harbouring and developing cancer. Science
      and technology have evolved to a point where we are able to use our knowledge of
      cancer biology to identify individuals at risk and interrupt the process of
      malignant transformation at the level of the pre-cancerous lesion. Recent
      progress in molecular biology and pharmacology enhances the likelihood that
      cancer prevention will increasingly rely on chemoprevention. Chemoprevention, a
      new emerging science, means the use of agents to inhibit, delay or reverse
      carcinogenesis. Recent observations suggest a number of potential targets for
      chemoprevention. Many agents have potential benefit, but only modest
      chemopreventive efficacy in clinical trials. There is much evidence suggesting an
      inverse relationship between aspirin or NSAIDs consumption and CRC incidence and
      mortality. However, NSAID consumption is not problem-free, as 1997 data showed
      107,000 hospitalisations and 16,500 deaths due to NSAIDs consumption in the US
      alone. Therefore, although chemoprevention of CRC is already possible, drugs that
      have more acceptable side-effect profiles than the currently available NSAIDs are
      required. COX-2-specific inhibitors, which have an improved safety profile, as
      compared to traditional NSAIDs that inhibit both the COX-1 and COX-2 enzymes,
      seem to be well suited drug candidates for CRC prevention. The inhibition of the
      growth of pre-cancerous and cancerous cells without affecting normal cells is the
      ultimate aim of cancer treatment and is of particular importance in
      chemoprevention studies, which may be long term in nature, involve healthy
      subjects and minimal toxicity. Cancer prevention is certain to be a significant
      focus of research and intervention in the coming years, propelled by the
      realization that we will be able to identify both individuals susceptible to
      specific cancers as well as the molecular targets that can alter or stop the
      carcinogenesis process. Pharmacology and genetics are collaborating to develop
      new chemoprevention agents designed to affect molecular targets linked to
      specific pre-malignant or predisposing conditions.

PMID- 15974948
TI  - Engineering chemokines to develop optimized HIV inhibitors.
AB  - Since the discovery that to enter target cells HIV uses receptors for the class
      of proteins known as chemokines, attempts have been made to generate anti-HIV
      molecules based on the chemokine ligands. A significant level of knowledge of the
      structure-activity relationships of chemokines has been amassed since the
      beginning of the 1990s. This, together with work that has elucidated the
      mechanisms underlying the inhibitory activity of chemokines, has guided not only
      the rational design of anti-HIV chemokine analogues, but also strategies by which
      chemokine variants with potent anti-HIV activity can be isolated from large
      libraries by phage display. This review summarizes the current knowledge about
      the structure-activity relationships and receptor biology of chemokines that is
      relevant to the development of analogues with anti-HIV activity. We present
      specific examples of engineered chemokine analogues with potent anti-HIV activity
      and describe the challenges that will need to be faced if these molecules are to
      be further developed for clinical applications. Finally, we discuss how these
      challenges might be met through further engineering of the molecules.

PMID- 15974949
TI  - Conotoxins as research tools and drug leads.
AB  - The complex mixture of biologically active peptides that constitute the venom of
      Conus species provides a rich source of ion channel neurotoxins. These peptides,
      commonly known as conotoxins, exhibit a high degree of selectivity and potency
      for different ion channels and their subtypes making them invaluable tools for
      unravelling the secrets of the nervous system. Furthermore, several conotoxin
      molecules have profound applications in drug discovery, with some examples
      currently undergoing clinical trials. Despite their relatively easy access by
      chemical synthesis, rapid access to libraries of conotoxin analogues for use in
      structure-activity relationship studies still poses a significant limitation.
      This is exacerbated in conotoxins containing multiple disulfide bonds, which
      often require synthetic strategies utilising several steps. This review will
      examine the structure and activity of some of the known classes of conotoxins and
      will highlight their potential as neuropharmacological tools and as drug leads.
      Some of the classical and more recent approaches to the chemical synthesis of
      conotoxins, particularly with respect to the controlled formation of disulfide
      bonds will be discussed in detail. Finally, some examples of structure-activity
      relationship studies will be discussed, as well as some novel approaches for
      designing conotoxin analogues.

PMID- 15974950
TI  - Serine proteinase inhibitors in the skin: role in homeostasis and disease.
AB  - Serine proteinases fulfill and facilitate a broad spectrum of biological
      processes. They are held in check by different specific inhibitors. This delicate
      balance can be disturbed by genetic defects or exogenous influences and has been
      shown as the underlying or promoting cause for a large number of different
      diseases. For instance, proteinases are under investigation as drug targets for
      cancer, infections, neurodegenerative diseases, osteoporosis, inflammatory
      disorders and many more. Dermatological research has contributed greatly to the
      appreciation of the complex regulatory network between serine proteinases and
      serine proteinase inhibitors. In addition, proteolytically trimmed proteinase
      activated receptors (PARs) trigger keratinocyte proliferation and differentiation
      as well as leukocyte attraction and activation. New insights have been gained
      particularly concerning the progression of inflammatory disorders of the skin.
      This review summarizes the role of serine proteinase inhibitors in physiology and
      pathophysiology of the skin.

PMID- 15974951
TI  - Functions of antimicrobial peptides in host defense and immunity.
AB  - Antimicrobial peptides (AMPs) are effector molecules of the innate immune system.
      AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction
      with biomembranes. Besides their direct antimicrobial function, they have
      multiple roles as mediators of inflammation with impact on epithelial and
      inflammatory cells influencing diverse processes such as cytokine release, cell
      proliferation, angiogenesis, wound healing, chemotaxis, immune induction, and
      protease-antiprotease balance. Furthermore, AMPs qualify as prototypes of
      innovative drugs that may be used as antibiotics, anti-lipopolysaccharide drugs,
      or modifiers of inflammation. This review summarizes the current knowledge about
      the basic and applied biology of antimicrobial peptides and discusses features of
      AMPs in host defense and inflammation.

PMID- 15974952
TI  - Discovery of novel regulatory peptides by reverse pharmacology: spotlight on
      chemerin and the RF-amide peptides metastin and QRFP.
AB  - Reverse pharmacology is a screening technology that matches G protein-coupled
      receptors (GPCRs) with unknown cognate ligands in cell-based screening assays by
      detection of agonist-induced signaling pathways. One decade spent pursuing orphan
      GPCR screening by this technique assigned over 30 ligand/receptor pairs and
      revealed previously known or novel undescribed ligands, mostly of a peptidic
      nature. In this review, we describe the discovery, characterization of the
      structural composition, biological function, physiological role and therapeutic
      potential of three recently identified peptidic ligands. These are metastin, QRFP
      in a context of five RF-amide genes described in humans and the chemoattractant,
      chemerin. Metastin was initially characterized as a metastasis inhibitor.
      Investigations using ligand/receptor pairing revealed that metastin was involved
      in a variety of physiological processes, including endocrine function during
      pregnancy and gonad development. The novel RF-amide QRFP is implicated in food
      intake and aldosterone release from the adrenal cortex in the rat. Chemerin,
      first described as TIG2, is upregulated in tazarotene-treated psoriatic skin. By
      GPCR screening, bioactive chemerin was isolated from ovarial carcinoma fluid as
      well as hemofiltrate. Characterization as a chemoattractant for immature
      dendritic cells and analysis of the expression profile of metastin and its
      receptor suggested a physiological role of chemerin as a mediator of the immune
      response, inflammatory processes and bone development.

PMID- 15974953
TI  - Hepcidin in iron metabolism.
AB  - Hepcidin, which has been recently identified both by biochemical and genomic
      approaches, is a 25 amino acid polypeptide synthesized mainly by hepatocytes and
      secreted into the plasma. Besides its potential activity in antimicrobial
      defense, hepcidin plays a major role in iron metabolism. It controls two key
      steps of iron bioavailability, likely through a hormonal action: digestive iron
      absorption by enterocytes and iron recycling by macrophages. In humans, this
      could explain that low levels of hepcidin found during juvenile haemochromatosis
      and HFE-1 genetic haemochromatosis are associated with an iron overload
      phenotype. Conversely, an increase of hepcidin expression is suspected to play a
      major role in the development of anemia of chronic inflammatory diseases.
      However, the regulatory mechanisms of hepcidin expression are multiple, including
      iron-related parameters, anemia, hypoxia, inflammation and hepatocyte function.
      Therefore, many physiological and pathological situations may modulate hepcidin
      expression and subsequently iron metabolism. A better knowledge of the biological
      effects of hepcidin and of its expression regulatory mechanisms will clarify the
      place of hepcidin in the diagnosis and treatment of iron-related diseases.

PMID- 15974955
TI  - Experimental antioxidant biotherapy for protection of the vascular wall by
      modified forms of superoxide dismutase and catalase.
AB  - The antithrombotic activities of superoxide dismutase and catalase are determined
      by their effects on reactive oxygen species. Modification of these enzymes with
      chondroitin sulphate enhances the effect due to accumulation of the derivatives
      on the surface of the vascular wall cells. We have shown that the effects of
      covalently modified biocatalysts exceed those of native enzymes, free chondroitin
      sulphate and their mixtures. The superoxide dismutase-chondroitin sulphate
      conjugate markedly reduced the thrombus mass, while the catalase-chondroitin
      sulphate conjugate predominantly preserved blood flow. The magnitude and duration
      of the antithrombotic activity of modified enzymes in a rat arterial thrombosis
      model allows one to expect a considerable protective effect after their combined
      application. A single-bolus intravenous injection of the combination between
      superoxide dismutase-chondroitin sulphate and catalase-chondroitin sulphate
      covalent conjugates had a significantly lower antithrombotic effect compared with
      that of the superoxide dismutase-chondroitin sulphate-catalase bienzymic covalent
      conjugate. This could be explained by different surface distribution of the
      conjugates in the circulation after their intravenous administration. Biomedical
      study of this approach promises a new therapeutic strategy of simple and
      effective protection of the vascular wall against various injuries with the use
      of the covalent conjugate superoxide dismutase-chondroitin sulphate-catalase. The
      review analyses the trends of combined application of enzyme preparations to
      enhance the effect of antioxidant therapy and to develop conjunctive courses of
      thrombolytic treatment.

PMID- 15974956
TI  - Role of antioxidants in atherosclerosis: epidemiological and clinical update.
AB  - Low density lipoprotein (LDL) oxidative modification in the vascular wall seems
      to be a key factor in atherosclerosis development. Oxidised LDLs might recruit
      monocytes and favour their transformation into foam cells through a receptor
      mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic
      potential which is probably responsible for endothelial cell damage and
      macrophage degeneration in the atherosclerotic human plaque. Following the
      oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e.
      Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of
      epidemiological, clinical and experimental studies. Animal studies indicate that
      dietary antioxidants may reduce atherosclerosis progression, and observational
      data in humans suggest that antioxidant vitamin ingestion is associated with
      reduced cardiovascular disease, but the results of randomised controlled trials
      are mainly disappointing. It has been suggested that natural antioxidants may be
      effective only in selected subgroups of patients with high levels of oxidative
      stress or depletion of natural antioxidant defence systems. The favourable
      effects shown by some studies relating antioxidant dietary intake and
      cardiovascular disease, may have been exerted by other chemicals present in
      foods. Flavonoids are the ideal candidates, since they are plentiful in foods
      containing antioxidant vitamins (i.e. fruits and vegetables) and are potent
      antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects
      on multiple mechanisms involved in atherosclerosis. Future studies should
      probably select patients in a context of high-oxidative stress / low-antioxidant
      defence, to verify if antioxidants may really prove useful as therapeutic anti
      atherosclerotic agents.

PMID- 15974957
TI  - Oxidative stress, antioxidants and neurodegenerative diseases.
AB  - It is widely accepted that oxidative stress increases with age, and that age is a
      major risk factor for several neurodegenerative diseases such as Parkinson's
      disease and Alzheimer's disease. An inbalanced overproduction of reactive oxygen
      species can induce neuronal damage, leading to neuronal death by necrosis or
      apoptosis. Antioxidants are consequently considered to be a promising approaches
      to neuroprotection. Although experimental data are consistent in demonstrating a
      neuroprotective effects of antioxidants in vitro and in animal models, the
      clinical evidence that antioxidants agents may prevent or slow the course of
      these diseases is still relatively unsatisfactory, and unsufficient to strongly
      modify the clinical practice. This review summarizes the available data from
      experimental studies and clinical trials on antioxidant neuroprotection in
      Parkinson's and Alzheimer's disease.

PMID- 15974958
TI  - Oxidants in asthma and in chronic obstructive pulmonary disease (COPD).
AB  - Experimental and clinical evidences suggest that oxidants play a role in the
      pathogenesis of respiratory disorders characterised by chronic airway
      inflammation such as asthma and chronic obstructive pulmonary disease (COPD). The
      respiratory system is chronically exposed to environmental pollutants, including
      oxidants. Exogenous sources of oxidants are particularly relevant to the
      pathogenesis of COPD, being cigarette smoke an extremely rich source of oxidants.
      In addition, the inflammatory cells recruited to the airways of patients with
      asthma and COPD, have an exceptional capacity to produce oxidants. Many decades
      of research have produced a significant amount of data indicating pro-oxidative
      molecular mechanisms putatively relevant in the pathogenesis of the oxidative
      stress which characterises these diseases, both locally and systemically. As a
      consequence, a drug therapy able to restore the redox imbalance in asthma and
      COPD would probably exert clinical and functional benefits. Indeed, currently
      available therapies for asthma and COPD can exert an inhibitory effect on oxidant
      production in the airways. However, it is unknown whether the efficacy of the
      treatment is somehow linked to the pharmacological modulation of the
      oxidant/antioxidant balance. So far, it appears that the potential role of
      antioxidant compounds in the treatment of asthma and COPD has not been fully
      explored.

PMID- 15974959
TI  - Management of the menopausal disturbances and oxidative stress.
AB  - Women frequently seek gynaecologic medical advice at menopause and require
      pharmacologic interventions to control subjective vasomotor complaints and to
      prevent late severe organic complications, which may effect the genitourinary
      tract, the skeletal, the cardiovascular and the nervous system. Depending on the
      severity of the presentation and the involvement of additional systems beyond the
      reproductive tract, physicians have several distinct therapies available, which
      should be carefully evaluated and administered in a "patient-personalised"
      fashion: they include organ-oriented drugs, available for selective treatment in
      patients which do not display major direct endocrine symptoms, as well as
      endocrine therapies (administration of native estrogens; or synthetic selective
      hormonal drugs, i.e. SERMs and SEEMs). Much interest is now focusing on new kinds
      of plant estrogen-like compounds, mostly isoflavones, which by one hand display
      estrogen-like (or antagonistic) effects, by the other are powerful antioxidising
      agents. In our survey, we discuss extensively the enormous amount of data
      available in the literature, underlining by one side that most of the
      formulations currently in use for the overall therapy of menopausal complaints
      have structure features also characteristic of antioxidising agents, by the other
      that there are wide evidences of increased oxidative damage occurs in women
      during the postmenopausal life. These observations suggest the possibility of a
      contribution of antioxidising activity of the administered drugs to the
      beneficial clinical effects on the patients, in agreement with the demonstrated
      estrogen intrinsic antioxidising activity in vitro. This stresses the requirement
      of further basic and clinical studies on the relevance of oxidative damage during
      postmenopausal female life.

PMID- 15974960
TI  - The role and modulation of the oxidative balance in pregnancy.
AB  - Oxidative processes exert a fundamental regulatory function during pregnancy. It
      depends on the influence of oxygen, nitric oxide, reactive oxygen species and
      reactive nitrogen species metabolic pathways upon the vascular changes in the
      maternal organism, as well as on the regulation of uterine and cervical tone
      throughout gestation and delivery. These functions are strictly linked with the
      mediators of the inflammatory pathway. At the beginning of pregnancy, when a
      certain grade of inflammatory change is necessary to the trophoblast invasion of
      maternal tissue, the activation of the process by nitric oxide and reactive
      nitrogen species is welcome. Indeed, these products modulate the
      metalloproteinases, which are responsible for the remodelling of uterine
      extracellular matrix. At this stage estrogens are involved as well in the
      regulation of the delicate balance of pro-oxidant and anti-oxidant effects.
      Furthermore, reactive oxygen and nitrogen species appear to play an important
      role both in normal and pathologic embryogenesis. During advanced pregnancy, a
      derangement of the oxidative balance can lead to the improper activation of
      inflammatory changes, thus triggering premature labour as well as other
      complications, such as foetal growth restriction and preeclampsia. Although a
      number of pro- and anti-oxidant agents are available to influence the above
      mentioned processes, there is no way to adequately measure the oxidative needs in
      single cases, in order to modulate the oxidative balance in clinical practice.
      Pharmacological research should be addressed to the development of new drugs, as
      well as to selective methods of delivery to the gestational tissues.

PMID- 15974961
TI  - Metallic colloid nanotechnology, applications in diagnosis and therapeutics.
AB  - In recent years the fields of medicine and biology assist to an ever-growing
      innovation related to the development of nanotechnologies. In the pharmaceutical
      domain, for example, liposomes, polymer based micro and nanoparticles have been
      subjects of intense research and development during the last three decades. In
      this scenario metallic particles, which use was already suggested in the first
      half of the '80, are now experiencing a real renaissance. In the field of
      diagnosis, magnetic resonance imaging is one of the first and up to now the most
      developed application of metallic particles. But beside this application, a very
      new generation of biosensors based on the optical properties of colloidal gold
      and fluorescent nanocrystals, called quantum dots seems to be ready to be
      implemented in diagnosis and medical imaging. Concerning therapeutic
      applications, the potentialities of metal nanoparticles to help fulfilling the
      need of time and space controlled release of drugs has been intuited for a long
      time. Nowadays, magnetically guided carriers or thermal responsive matrices, in
      which drug release is triggered by the heating of metal nanoparticles, are
      effective examples of their application in drug delivery, while more recently
      efforts to develop metallic nanoobjects to be used as vectors of nucleic acids
      for vaccination and transfection have been multiplied. In the future, one of the
      most interesting challenges is certainly the use of metallic nanoparticles for an
      innovating, effective and selective physical treatment of solid tumors via
      targeted intracellular hyperthermia.

PMID- 15974962
TI  - Triple treatment with octreotide, galanin and serotonin is a promising therapy
      for colorectal cancer.
AB  - In patients with colorectal cancer, low levels of colonic somatostatin, galanin
      and serotonin have been found. Based on these findings, the effects of triple
      treatment with octreotide (a somatostatin analogue), galanin and serotonin on
      colorectal cancer has been studied. Triple therapy was found to reduce the volume
      and weight of both rat and human colon carcinoma in xenografts, apparently by
      necrosis, but also by reducing proliferation and expression of epidermal growth
      factor of cancer cells, and also by inducing apoptosis. It has been suggested
      that tumour necrosis results from ischemia in the tumour caused by a reduction in
      the tumour blood flow, a consequence of reduced number of tumour-feeding blood
      vessels and by constricting of tumour feeding arterioles. The effects of treating
      rat colorectal cancer using single, double and triple therapy with octreotide,
      galanin and serotonin were studied. Of these substances, galanin alone achieved a
      significant reduction in tumour-feeding blood vessels. Single and double regimes
      had some effect, but were not nearly so successful as triple treatment. The
      optimum treatment dose of triple therapy lies between 40 and 80 microg/kg/day,
      smaller doses had no effect on the tumours at all, while larger doses had no
      additional effect. The optimal administration route is continuous i.p. infusion,
      for 14 days. Triple therapy gave no obvious side effects, and had equivalent anti
      tumour and therapeutic efficacy as standard treatment with 5
      fluorouracil/leucovorin. Although this treatment appears to be a promising
      option, clinical trials need be conducted to establish whether it can be
      beneficial in clinical use.

PMID- 15974963
TI  - Integrin function and signaling as pharmacological targets in cardiovascular
      diseases and in cancer.
AB  - The microenvironment is now considered as an important source of potential
      therapeutic targets in diverse pathologies. In cardiovascular diseases and in
      cancer, common processes involving stromal remodeling, cell invasion, and
      angiogenesis can promote progression of the pathology. At each step of the
      pathogenesis, cell adhesion needs to be modulated to allow adaptation of cell
      survival/motility/proliferation functions to the microenvironment. Among adhesion
      receptors, integrins, responsible for cell/matrix or cell/cell interactions, play
      a key role in the cellular responses. Moreover, their engagement conditions the
      sensitivity to apoptosis induced by therapeutic drugs. Targeting of the
      extracellular side of integrins in order to modulate their adhesive functions is
      under development and has reached clinical indications. However, improvement of
      oral availability and of cell signaling control is required in the future.
      Targeting of the extracellular or the intracellular key proteins involved in
      integrin-dependent signaling pathway seems promising. Yet, although some common
      key enzyme inhibitors are under development, a better knowledge of the
      specificity of integrin activation and interaction with partners upon
      pathogenesis is of major importance in envisaging the antagonism of integrin
      linked signals as a therapeutic tool alone or in association with other
      therapies.

PMID- 15974964
TI  - Membrane channels as therapeutic targets.

PMID- 15974965
TI  - GABA(A) receptor channel pharmacology.
AB  - GABA(A) receptor channels are ubiquitous in the mammalian central nervous system
      mediating fast inhibitory neurotransmission by becoming permeant to chloride ions
      in response to GABA. The emphasis of this review is on the rich chemical
      diversity of ligands that influence GABA(A) receptor function. Such diversity
      provides many avenues for the design and development of new chemical entities
      acting on GABA(A) receptors. There is also a significant diversity of GABA(A)
      receptor subtypes composed of different protein subunits. The discovery of
      subtype specific agents is a major challenge in the continuing development of
      GABA(A) receptor pharmacology. Leads for the discovery of new chemical entities
      that influence GABA(A) receptors come from using recombinant GABA(A) receptors of
      known subunit composition as has been elegantly demonstrated by the refining of
      benzodiazepine actions with alpha1 subunit preferring agents showing sedative
      properties but not anxiolytic properties. The most recent advances in the
      therapeutic use of agents acting on GABA(A) receptors concern the promotion of
      sound sleep. Many herbal medicines are used to promote sleep and many of their
      active ingredients include flavonoids and terpenoids known to modulate GABA(A)
      receptor function.

PMID- 15974966
TI  - Molecular pharmacology of non-L-type calcium channels.
AB  - Voltage-gated calcium channels are key sources of calcium entry into the cytosol.
      Mutations in calcium channels have been implicated in numerous disorders such as
      migraine, incomplete congenital X-linked stationary night blindness, epilepsy,
      and ataxia, and they are important therapeutic targets for the treatment of pain,
      stroke, hypertension, and epilepsy. Calcium channel antagonists can be broadly
      classified into three groups. 1) Inorganic ions typically nonselectively block
      the pore of most calcium channel subtypes, and in some cases, alter gating
      kinetics. 2) Peptides isolated from arachnids, cone snails, and snakes frequently
      selectively antagonize individual calcium channel subtypes by direct occlusion of
      the pore or altering gating kinetics. 3) Small organic molecules of various
      structure-activity-relationship (SAR) classes can mediate both selective and
      nonselective effects on individual calcium channel subtypes, and occlude the pore
      or reduce channel availability. Here, we provide an overview of classes of
      inhibitors of non-L-type calcium channels.

PMID- 15974967
TI  - TRP channels as a newly emerging non-voltage-gated CA2+ entry channel
      superfamily.
AB  - It has long been known that many chemical and physical stimuli imposed on the
      cell from its exterior environments elicit a long-lasting Ca2+ influx through yet
      poorly elucidated transmembrane pathways distinct from voltage-gated and fast
      ligand-gated Ca2+ entry channels, thereby activating and modulating a variety of
      cellular functions. Recent progress in molecularly identifying these pathways,
      initiated from the discovery of Drosophila's visual transduction mutants
      transient receptor potential (TRP) proteins, has begun to reveal the presence of
      an enormous superfamily of non-voltage-gated Ca2+ channels. The mammalian members
      of TRP superfamily are (except for two members) Ca2+-permeable non-selective
      cation channels which are constitutively active or gated by a multitude of
      physicochemical stimuli such as receptor stimulation, phospholipids, oxidants,
      pheromones, cell volume change/shear stress, exogenous compounds affecting
      sensations, and changes in ambient temperature, acidity and osmolarity and
      cellular metabolic status. Owing to these diversities in activation and their
      broad distribution from brain to peripheral organs and tissues, TRP channels are
      now thought to be involved in divergent physiological functions including; pain
      and taste transductions; thermo- and mechano-sensations; regulation of mineral
      absorption/reabsorption; blood pressure, gut motility and airway responsiveness;
      cell proliferation/death, some of which seem tightly associated with specific
      genetic disorders. These features will render TRP channels the attractive novel
      molecular targets for future drug therapy. This paper briefly overviews the
      current knowledge available for these channels with a main interest in their
      possible linkage with in vivo function.

PMID- 15974968
TI  - ATP-sensitive potassium channels.
AB  - ATP-sensitive potassium (K(ATP)) channels link membrane excitability to
      metabolism. They are regulated by intracellular nucleotides and by other factors
      including membrane phospholipids, protein kinases and phosphatases. K(ATP)
      channels comprise octamers of four Kir6 pore-forming subunits associated with
      four sulphonylurea receptor subunits. The exact subunit composition differs
      between the tissues in which the channels are expressed, which include pancreas,
      cardiac, smooth and skeletal muscle and brain. K(ATP) channels are targets for
      antidiabetic sulphonylurea blockers, and for channel opening drugs that are used
      as antianginals and antihypertensives. This review focuses on non-pancreatic
      K(ATP) channels. In vascular smooth muscle, K(ATP) channels are extensively
      regulated by signalling pathways and cause vasodilation, contributing both to
      resting blood flow and vasodilator-induced increases in flow. Similarly, K(ATP)
      channel activation relaxes smooth muscle of the bladder, gastrointestinal tract
      and airways. In cardiac muscle, sarcolemmal K(ATP) channels open to protect cells
      under stress conditions such as ischaemia or exercise, and appear central to the
      protection induced by ischaemic preconditioning (IPC). Mitochondrial K(ATP)
      channels are also strongly implicated in IPC, but clarification of their exact
      role awaits information on their molecular structure. Skeletal muscle K(ATP)
      channels play roles in fatigue and recovery, K+ efflux, and glucose uptake, while
      neuronal channels may provide ischaemic protection and underlie the glucose
      responsiveness of hypothalamic neurones. Current therapeutic considerations
      include the use of K(ATP) openers to protect cardiac muscle, attempts to develop
      openers selective for airway or bladder, and the question of whether block of
      extra-pancreatic K(ATP) channels may cause adverse cardiovascular side-effects of
      sulphonylureas.

PMID- 15974969
TI  - Connexin-made channels as pharmacological targets.
AB  - Gap junctions are clusters of intercellular channels that provide morphological
      support for direct diffusion of ions and low-molecular-weight molecules between
      adjacent coupled cells. Each gap junction channel is made by docking of two
      hemichannels or connexons, each formed by assembly of six proteins (connexins).
      21 members of the connexin gene family are likely to be expressed in the human
      genome. These ubiquitous gated channels, allowing rapid intercellular
      communication and synchronisation of coupled cell activities, play critical roles
      in many signalling processes, including co-ordinated cardiac and smooth muscle
      contractions, neuronal excitability, neurotransmitter release, insulin secretion,
      epithelial electrolyte transport, etc. Mutational alterations in the connexin
      genes are associated with the occurrence of multiple pathologies, such as
      peripheral neuropathies, cardiovascular diseases, dermatological diseases,
      hereditary deafness and cataract. But the neuro- and cardioprotective effects of
      blocking agents of junctional channels show that closure of these channels may
      also be beneficial in certain pathological situations. Consequently, modulation
      of gap junctional intercellular communication is a potential pharmacological
      target. In contrast to most other membrane channels, no natural toxin or specific
      inhibitor of junctional channels has been identified yet and most uncoupling
      agents generally also affect other ionic channels and receptors. Future research,
      based for example on the recent developments in genetics, may clarify gap
      junction physiology. This will in turn provide promising perspectives for the
      development of targeted drugs.

PMID- 15974970
TI  - Novel targets for cardiac antiarrhythmic drug development.
AB  - Cardiac arrhythmias remain a major source of morbidity and mortality in developed
      countries. Antiarrhythmic drug therapy was traditionally the mainstay of cardiac
      arrhythmia treatment; however, drug therapy of cardiac arrhythmias has been
      plagued by incomplete efficacy and by potentially serious adverse reactions, of
      which the most worrisome has been a potential for malignant proarrhythmia and
      related effects to increase cardiac mortality. This article reviews the principal
      arrhythmia mechanisms and their ionic determinants, and discusses potential
      innovative approaches to new antiarrhythmic drug development, including the
      consideration of novel ionic targets, potential biophysical approaches and non
      channel components involved in composing the arrhythmic substrate.

PMID- 15974971
TI  - Ion channels and epilepsy.
AB  - The role of voltage-gated and ligand-gated ion channels in epileptogenesis of
      both genetic and acquired epilepsies, and as targets in the development of new
      antiepileptic drugs (AEDs) is reviewed. Voltage-gated Na+ channels are essential
      for action potentials, and their mutations are the substrate for generalised
      epilepsy with febrile seizures plus and benign familial neonatal infantile
      seizures; Na+ channel inhibition is the primary mechanism of carbamazepine,
      phenytoin and lamotrigine, and is a probable mechanism for many other classic and
      novel AEDs. Voltage-gated K+ channels are essential in the repolarisation and
      hyperpolarisation that follows paroxysmal depolarisation shifts (PDSs), and their
      mutations are the substrate for the benign neonatal epilepsy and episodic ataxia
      type 1; they are new targets for AEDs such as retigabine. Voltage-gated Ca2+
      channels are involved in neurotransmitter release, in the sustained
      depolarisation-phase of PDSs, and in the generation of absence seizures; their
      mutations are a substrate for juvenile myoclonic epilepsy and the absence-like
      pattern seen in some mice; the antiabsence effect of ethosuximide is due to the
      inhibition of thalamic T-type Ca2+ channels. Voltage-gated Cl- channels are
      implicated in GABA(A) transmission, and mutations in these channels have been
      described in some families with juvenile myoclonic epilepsies, epilepsy with
      grand mal seizures on awakening or juvenile absence epilepsy. Hyperpolarisation
      activated cation channels have been implicated in spike-wave seizures and in
      hippocampal epileptiform discharges. The Cl- ionophore of the GABA(A) receptor is
      responsible for the rapid post-PDS hyperpolarisation, it has been involved in
      epileptogenesis both in animals and humans, and mutations in these receptors have
      been found in families with juvenile myoclonic epilepsy or generalised epilepsy
      with febrile seizures plus; enhancement of GABA(A) inhibitory transmission is the
      primary mechanism of benzodiazepines and phenobarbital and is a mechanistic
      approach to the development of novel AEDs such as tiagabine or vigabatrin.
      Altered GABA(B)-receptor function is implicated in spike-wave seizures.
      Ionotropic glutamate receptors are implicated in the sustained depolarisation
      phase of PDS and in epileptogenesis both in animals and humans; felbamate,
      phenobarbital and topiramate block these receptors, and attenuation of
      glutamatergic excitatory transmission is another new mechanistic approach.
      Mutations in the nicotinic acetylcholine receptor are the substrates for the
      nocturnal frontal lobe epilepsy. The knowledge of the role of the ion channels in
      the epilepsies is allowing the design of new and more specific therapeutic
      strategies.

PMID- 15974973
TI  - Stability assessment of pharmaceuticals and biopharmaceuticals by isothermal
      calorimetry.
AB  - The assessment of stability (of actives, excipients and/or formulated products)
      is an important, and often time-consuming, part of pharmaceutical product
      development. Conventionally, HPLC is used to quantify the concentrations of a
      parent compound and any degradation products as a function of storage time. HPLC,
      however, is relatively insensitive to small changes in concentration and it is
      often the case that stability assays are conducted under stress conditions, in
      order to accelerate any degradation processes. The Arrhenius relationship is then
      employed to give an initial prediction of stability under storage conditions
      while long-term studies, under storage conditions, are conducted to confirm these
      predictions. The properties of isothermal calorimetry, such as its intrinsic
      sensitivity to small changes in heat and invariance to the physical form of a
      sample, make it ideally suited for stability assessment because it obviates the
      need for an Arrhenius analysis. In addition, the ability to conduct titration or
      gas perfusion experiments vastly increases its range of applications. Recent
      advances in instrumental design and data analysis have made it easier to analyse
      data quantitatively for complex systems. It is the purpose of this review to
      highlight some of these developments, discuss them in the context of
      pharmaceutical and biopharmaceutical examples and explore some of the future
      challenges and applications of the technique.

PMID- 15974974
TI  - Characterization of pharmaceutical polymorphs by isothermal calorimetry.
AB  - A great number of pharmaceutical substances exist in crystalline solid-state.
      Because of the complexity of their chemical structure many different polymorphs
      of a given substance can exist. Polymorphic forms of solid pharmaceuticals
      influence not only their dissolution behavior, i.e. bioavailability but also
      their solid-state stability. It is well known that only one polymorphic form is
      thermodynamically stable and all other metastable forms will convert, eventually,
      to the more stable form. Hence it is essential to choose the most suitable
      polymorphic form in the early stage of pharmaceutical development. The following
      article reviews the recent applications of solution calorimetry that allows
      characterization of pharmaceutical polymorphs through accurate determination of
      enthalpy of solution. Each crystalline form possesses a defined enthalpy of
      solution, therefore solution calorimetry is used for the quantitative analysis of
      the desired polymorphic form and determination of enthalpy of transition
      corresponding to the difference in enthalpies of solution for a polymorphic pair.
      More recently this technique has been applied to the estimation of thermodynamic
      transition temperature, which is useful for the evaluation of thermodynamic
      stability relationships between polymorphs. This article will also describe the
      kinetics and thermodynamics of polymorphic transitions, from a metastable form to
      the thermodynamically stable form, through studies using ampoule-based isothermal
      microcalorimetry. Such studies are particularly useful when metastable forms are
      to be selected in order to enhance bioavailability. If the metastable form, or
      the pharmaceutical product containing it, can be shown to be sufficiently stable,
      it could then be used in a formulation where its therapeutic effects could be
      exploited.

PMID- 15974975
TI  - Recent developments for the analysis of data obtained from isothermal
      calorimetry.
AB  - Isothermal calorimetry is rapidly becoming an indispensable tool for the
      quantitative determination of a variety of kinetic and thermodynamic parameters
      for a wide range of systems. In particular calorimetry is finding increased
      application to the investigation of stability and incompatibility of
      pharmaceutical materials. In order to draw meaningful conclusions and to predict
      behaviour in related systems it is necessary to have the means to calculate
      accurately parameters such as the rate constant and enthalpy. To this end several
      groups have been developing equations which describe calorimetric output in these
      terms. This paper will briefly outline some of these equations and discuss some
      of the limitations that currently exist in their application. A particular
      emphasis is placed on the recent developments relating to the application of
      these equations to flow calorimetric data. The main application of these
      equations is usually found in the pharmaceutical industry. Pharmaceutical
      formulations are usually extremely complex mixtures consisting of many different
      excipients as well as the active drug. Because of these large numbers of
      ingredients it is often observed that multiple chemical and physical process
      occur over the lifetime of the study. This complexity is then reflected in the
      calorimetric data rendering the application of the simple equations useless.
      Dealing with this complexity is a major issue amongst the calorimetric community
      and some of the recent advances in this field are also discussed.

PMID- 15974976
TI  - Application of solution calorimetry in pharmaceutical and biopharmaceutical
      research.
AB  - In solution calorimetry the heat of solution (Delta(sol)H) is recorded as a
      solute (usually a solid) dissolves in an excess of solvent. Such measurements are
      valuable during all the phases of pharmaceutical formulation and the number of
      applications of the technique is growing. For instance, solution calorimetry is
      extremely useful during preformulation for the detection and quantification of
      polymorphs, degrees of crystallinity and percent amorphous content; knowledge of
      all of these parameters is essential in order to exert control over the
      manufacture and subsequent performance of a solid pharmaceutical. Careful
      experimental design and data interpretation also allows the measurement of the
      enthalpy of transfer (Delta(trans)H) of a solute between two phases. Because
      solution calorimetry does not require optically transparent solutions, and can be
      used to study cloudy or turbid solutions or suspensions directly, measurement of
      Delta(trans)H affords the opportunity to study the partitioning of drugs into,
      and across, biological membranes. It also allows the in-situ study of cellular
      systems. Furthermore, novel experimental methodologies have led to the increasing
      use of solution calorimetry to study a wider range of phenomena, such as the
      precipitation of drugs from supersaturated solutions or the formation of
      liposomes from phospholipid films. It is the purpose of this review to discuss
      some of these applications, in the context of pharmaceutical formulation and
      preformulation, and highlight some of the potential future areas where solution
      calorimetry might find applications.

PMID- 15974977
TI  - The analysis of microorganisms by microcalorimetry in the pharmaceutical
      industry.
AB  - Many features of microorganisms make them pre-eminently suitable for study by
      microcalorimetry. They have thus, in the past, been the basis of fundamental
      studies in metabolism and cellular physiology. In this review we look at the
      application of calorimetry to the impact of bacteria and fungi on the
      pharmaceutical industry both in the exploitation of useful microorganisms and the
      fight against harmful ones. Obviously they are of great relevance to the
      pharmaceutical industry as agents of human disease, with more antimicrobial
      products registered for production than for any other type of human affliction.
      Microcalorimetry offers the opportunity to study microorganisms in real time and
      in heterogeneous systems, allowing for more descriptive and representative
      analysis. Other advantages that microcalorimetry confers over traditional
      microbiological techniques are reductions in time, better reproducibility and
      simplicity. Also the manufacture of all pharmaceutical products requires the
      exclusion of microorganisms to a greater or lesser degree. The enumeration and
      identification of such contaminants is of great importance for the well-being of
      patients and to maintain the integrity of the product. New techniques are
      required to increase the reliability and sensitivity over conventional methods.
      Finally, as our understanding of biology develops, the sophistication of
      therapeutic agents available, such as vaccines, cytokines and engineered
      antibodies, is increasing. Necessarily, prokaryotic and eukaryotic cells,
      possibly transformed with the appropriate genes, are the producers of such
      proteins. Microcalorimetry offers a sensitive means of developing the conditions
      for optimum production of such products in active form since it gives
      instantaneous information on the physiology of the producer cell.

PMID- 15974978
TI  - Thermoanalytical techniques for the investigation of the freeze drying process
      and freeze-dried products.
AB  - A key challenge facing the pharmaceutical industry is the production of
      biotechnological drug products such as proteins in a stable form. Freeze-drying
      is preferred for manufacturing such products because of the low temperatures
      used. However, the protein may still degrade during the process necessitating the
      inclusion of a protectant. This review describes the range of thermal analysis
      techniques that have been used to investigate the properties of formulations to
      be freeze dried and the resultant products. This approach has allowed insight
      into the key parameters required for design of formulations and processes that
      will generate the best possible products.

PMID- 15974980
TI  - Synthetic carriers: sequential oligopeptide carriers SOCn-I and SOCn-II as an
      innovative and multifunctional approach.
AB  - Nowadays, the use of synthetic carriers as biochemical reagents and immunogens is
      entering a new phase. The multimeric nature of these constructs, the unambiguous
      composition and the ease, reliability and versatility of their production, make
      this type of carriers well-suited to various biotechnological and biochemical
      applications for diagnostic purposes, protein mimetics, antiviral agents,
      vaccines, drug and gene delivery vehicles. This review aims to briefly summarize
      the different types of synthetic carriers currently in use and will be focused on
      an innovative type of multifunctional helicoid carrier-foldamer, named SOC(n)-I,
      II, which was successfully developed in our laboratory. Our concept was to
      construct an artificial template with structural rigidity and regularity, so as
      the peptide epitopes/pharmacophore groups could be anchored without any
      conformational restriction and steric hindrance as demonstrated by conformational
      studies using (1)H-NMR, CD and FT-IR. SOC(n)-I,II were used as antigenic
      substrates in developing immunoassays of high sensitivity, specificity and
      reproducibility, as well as potent immunogens to generate site-specific
      antibodies. To this end, we emphasize on the application of SOC(n) carriers
      covalently bearing a 'built-in' adjuvant, for the preparation of totally
      synthetic peptide-based vaccines for human use.

PMID- 15974981
TI  - Insights into peptide-based vaccine design for cancer immunotherapy.
AB  - The presentation of peptides derived from tumor associated proteins (TAAs) by the
      major histocompatibility complex (MHC) to T cell receptor (TcR) initiates a
      cascade of events that constitute the immune response. Eliciting an effective
      immune response, however, requires the coordinated regulation of both the
      cellular and humoral arms of the immune system. The design of effective peptide
      based vaccines for cancer immunotherapeutic applications, therefore, requires
      intimate knowledge and understanding of peptide-MHC (pMHC) as well as TcR-pMHC
      interactions. Despite the wealth of information available to date from X-ray
      crystallographic and biological studies, the task of rationally designing peptide
      based vaccines that can effectively prevent and/or treat cancer cell
      proliferation remains challenging. The complexity of interactions involved are
      not readily predictable and are further complicated by the involvement of
      surrounding molecules in vivo, which can lead to reduced biological activity
      and/or unwanted side effects. Furthermore, the delivery of peptide-based vaccines
      into the cell, for further processing and presentation to effector cell,
      represents an additional challenge which needs to be addressed. The incorporation
      of appropriate chemical entities into peptide-based vaccines can improve cellular
      uptake thereby enhancing biological activity. Finally, the susceptibility of
      peptide-based vaccines to enzymatic degradation warrants the need for the
      incorporation of non-natural amino acids, retro-inversion and/or cyclization to
      improve bioavailability essentially reducing the required dosage with minimum
      side effects.

PMID- 15974982
TI  - Basement membrane peptides: functional considerations and biomedical applications
      in autoimmunity.
AB  - Basement membranes are specialized extracellular matrices that surround certain
      cell types (muscle cells, adipose cells, etc) and are present under the basal
      surface of cells exhibiting polarity (epithelial, endothelial and mesothelial
      cells). They have a unique macromolecular composition, consisting mainly of type
      IV collagen isoforms, laminin isoforms, entactin/nidogen, and perlecan. These
      components self associate and interact with each other to form networks. Other
      macromolecules may be found in specialized basement membranes. In this short
      review, the role of selected basement membrane proteins in autoimmune diseases
      will be highlighted. As an example, Goodpasture's syndrome will be presented and
      the relatively long quest for identification of the antigenic epitope on specific
      domains of the alpha3(IV)NC1 will be summarized. Chagas disease will be discussed
      as an example of laminin-mediated autoimmunity, with emphasis on the role of
      sugar-based antigenic epitope(s) will be presented. Immune-mediated
      tubulointerstitial nephritis will be introduced and the role of a synthetic
      peptide in detecting proximal tubule damage in acute renal failure will be
      discussed. Auto-immune diseases where other basement membrane macromolecules are
      involved will be mentioned. Finally, the importance of understanding the
      functions served by domains at close proximity to the antigenic epitope(s) will
      be highlighted.

PMID- 15974983
TI  - The corticotropin-releasing factor (CRF) family of neuropeptides in inflammation:
      potential therapeutic applications.
AB  - Hypothalamic CRF plays a central role in the coordination of endocrine and
      behavioral responses to stress and it is also involved in the pathophysiology of
      several neuropsychiatric diseases including depression, anxiety and addiction. In
      the mammals, the CRF family of peptides includes CRF, urocortin (Ucn), Ucn I, and
      Ucn II while was enriched with new members, the urocortins. Their biological
      effects are mediated by the CRF1 and CRF2 receptors, which belong to the G
      protein-coupled receptor super family. Multiple research groups have demonstrated
      during the last decade the expression of the CRF peptides and their receptors in
      several components of the immune system and their participation in the ad hoc
      regulation of inflammatory phenomena. Non-peptide CRF1 antagonists have been
      recently synthesized for the treatment of CNS related diseases, such as anxiety,
      depression and drug abuse. In the gastrointestinal tract, these compounds open
      new therapeutic options in the treatment of lower-GI inflammatory diseases
      associated to CRF, such as the chronic inflammatory bowel syndromes, irritable
      bowel disease and ulcerative colitis while Ucn, Ucn I, Ucn II or synthetic non
      peptide CRF2 agonists may be useful in the treatment of upper-GI inflammatory
      diseases. In human endometrium, CRF1 antagonists may be used as abortive agents
      interfering with the inflammatory phenomena taking place during the implantation
      of the conceptus. They thus may represent a new class of nonsteroidal inhibitors
      of implantation. These two examples illustrate the potential therapeutic
      significance of the CRH in regulating inflammatory phenomena in an ad hoc
      approach without affecting the rest of the immune system.

PMID- 15974984
TI  - Animal models of central nervous system immune-mediated diseases: therapeutic
      interventions with bioactive peptides and mimetics.
AB  - Experimental allergic encephalomyelitis (EAE) is a T helper 1 (Th1) mediated
      autoimmune disease and the principal animal model for multiple sclerosis (MS).
      Like MS, EAE is characterized by a coordinated inflammatory attack on the myelin
      sheath in the central nervous system (CNS), with damage to axons. No matter
      whether the ideal animal model is not yet available, much knowledge concerning
      the pathogenesis of MS has been achieved through studies on EAE. Dissecting the
      underlying immune mechanisms provided recognition of several myelin antigens that
      are vulnerable in autoimmune attack. The beneficial effect and the mechanism of
      action of a number of the currently used immunomodulating agents in MS therapy
      were first indicated in EAE. Altered peptide ligands (APL) can modulate T-cell
      responses to native peptide antigens implicated in the pathogenesis of autoimmune
      diseases such as MS and EAE. However, peptide therapy is hindered due to the
      sensitivity of peptides to proteolytic enzymes as well as due to some immune
      mediated side effects. A number of cyclic myelin peptide analogs seem to be
      potential candidates in maintaining the biological function of the original
      peptide and effective in controlling inflammation in EAE. Additional data
      regarding the immunomodulating and neuroprotective effect of these much promising
      agents is required. Based on the data from studies on EAE models, clinical trials
      should also be designed in order to elucidate the impact of such APL-induced
      immune responses in MS disease activity. These clinical trials should carefully
      incorporate monitoring of both clinical, neuroimaging and immunological
      parameters.

PMID- 15974985
TI  - Structural requirements for binding of myelin basic protein (MBP) peptides to MHC
      II: effects on immune regulation.
AB  - Confronting Multiple Sclerosis requires as an underlying step the manipulation of
      immune response through modification of Myelin Basic Protein peptides. The aim is
      to design peptidic or nonpeptidic molecules that compete for recognition of self
      antigens at the level of antigen presentation. The rational approach is to
      substitute residues that serve as anchors for the T-Cell Receptor with others
      that show no binding at all, and those that serve as Major Histocompatibility
      Complex II anchors with others that present increased binding affinity. The
      resulting structure, hence, retains normal or increased MHC II binding
      properties, but fails to activate disease-inducing T-cells. This rational design
      can only be achieved by identifying the structural requirements for binding of
      the natural peptide to MHC II, and the anchor residues with their corresponding
      specific pockets in the binding groove. The peptide-MHC II complex then interacts
      with the TCR; thus, an additional way to trigger the desired immune response is
      to alter secondary anchor residues as well as primary ones. In this review, the
      structural requirements for binding of MBP peptides to MHC II are presented, as
      are the mechanism and key features for TCR recognition of the peptide-MHC II
      complex.

PMID- 15974986
TI  - Advances in the treatment of autoimmune diseases; cellular activity, type-1/type
      2 cytokine secretion patterns and their modulation by therapeutic peptides.
AB  - Autoimmune diseases are many, have an overall prevalence of about 3% of the world
      population, affecting more women than men, and their incidence is influenced by
      genetics and the environment. It is currently thought that the immune response of
      a genetically predisposed individual to an environmental pathogen, under the
      influence of inadequate or non-functional immunoregulatory mechanisms, can lead
      to the development of an autoimmune disease. Advances in the treatment of
      autoimmune diseases follow a better understanding of the abnormalities in the
      cellular activity pathways and the resulting, often permanent, imbalance of the
      pro- and anti-inflammatory cytokine expression profiles. Over the past few years,
      there has been a dramatic change in the therapeutic regimens employed in
      autoimmune diseases, with soluble receptors, monoclonal antibodies and molecular
      mimetics enhancing or gradually replacing conventional immunosuppressive
      therapies. New biologicals have been developed, targeting defined pathways of the
      adaptive immune response. One approach towards the therapeutic management of
      autoimmune diseases involves the design and use of peptide analogs of disease
      associated epitopes to be used as immunomodulatory drugs. Peptides can target
      cell-functions directly, by interfering with the formation of the tri-molecular
      complex MHC-Peptide-TCR, and/or they can target soluble mediators such as
      cytokines or their receptors, eventually replacing monoclonal antibody therapies.
      This review offers an update on the treatment modalities of certain prototypic
      autoimmune diseases, based on the current knowledge of disease pathogenesis, with
      emphasis on cell activation and cytokine expression profiles.

PMID- 15974987
TI  - Conformational properties of HIV-1 gp120/V3 immunogenic domains.
AB  - Infection of target host cells by the human immunodeficiency virus-1 (HIV-1) is a
      multi-step process involving a series of conformational changes in the viral
      gp120 and gp41 proteins. Gp120 binding to the main cell receptor, CD4, on the
      surface of cells expressing this molecule, and interaction with the cell
      chemokine receptors CCR5 and CXCR4, are among the key events for HIV-1 infection.
      These steps are crucial for the virus and offer potential therapeutic targets.
      For this reason, understanding the structure and the physicochemical
      characteristics of the gp120 in relation to these interactions has drawn much
      attention. This review article focuses on the biologically important V3 region of
      the gp120 and summarizes the functional role, the sequence variation and the
      conformational features of V3 peptides, which are important for co-receptor
      selectivity, specificity and interaction. Synthetic V3 peptides have been
      extensively studied by NMR spectroscopy and X-ray crystallography, in solution or
      in solid state, in their free or bound form, and valuable information was
      generated with the aim to be exploited in the design of new, effective inhibitors
      of HIV-1 infection. The features of the potential gp120 interacting sites on the
      two chemokine co-receptors, CCR5 and CXCR4, are also discussed, and co-receptor
      blocking molecules under clinical trial are also reported.

PMID- 15974988
TI  - Structure and function of the myelin proteins: current status and perspectives in
      relation to multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) characterized by demyelination and loss of neurological function,
      local macrophage infiltrate and neuroantigen-specific CD4(+)T cells. MS arises
      from complex interactions between genetic, immunological, infective and
      biochemical mechanisms. Although the circumstances of MS etiology remain
      hypothetical, one persistent theme involves immune system recognition of myelin
      specific antigens derived from myelin basic protein, the most abundant extrinsic
      myelin membrane protein, and/or another equally suitable myelin protein or lipid.
      Knowledge of the biochemical and physico-chemical properties of myelin proteins
      and lipids, particularly their composition, organization, structure and
      accessibility with respect to the compacted myelin multilayers, becomes central
      to understanding how and why myelin-specific antigens become selected during the
      development of MS. This review focuses on the current understanding of the
      molecular basis of MS with emphasis: (i) on the physical-chemical properties,
      organization, morphology, and accessibility of the proteins and lipids within the
      myelin multilayers; (ii) on the structure-function relationships and
      characterization of the myelin proteins relevant to the manifestation and
      evolution of MS; (iii) on conformational relationships between myelin epitopes
      which might become selected during the development of MS; (iv) on the structure
      of MHC/HLA in complex with MBP peptides as well as with TCR, which is crucial to
      the understanding of the pathogenesis of MS with the ultimate goal of designed
      antigen-specific treatments.

PMID- 15974990
TI  - Current knowledge on the antagonists and inverse agonists of cannabinoid
      receptors.
AB  - Ten years elapsed since the discovery by Sanofi of SR141716A the first selective
      CB(1) cannabinoid receptor antagonist. Shortly after, Sanofi also reported the
      synthesis of the first selective CB(2) cannabinoid receptor antagonist, SR144528.
      Since these two milestones in the cannabinoid field, many other compounds, more
      or less related to the Sanofi compounds, or based on a completely different
      scaffold appeared. Several of these compounds are currently involved in clinical
      trials for diseases such as obesity, nicotine and alcohol addictions, or
      allergies. Further, the cannabinoid receptors knock-out mice production
      strengthened the hypothesis of the existence of several other "cannabinoid"
      receptors for which the first antagonists begin to appear. The large amount of
      patents taken by many different pharmaceutical companies prove, if necessary, the
      great therapeutic potential expected for the cannabinoid receptors antagonists.

PMID- 15974991
TI  - Recent developments in the medicinal chemistry of cannabimimetic indoles,
      pyrroles and indenes.
AB  - During the development of new nonsteroidal anti-inflammatory agents, it was
      discovered that 1-aminoalkyl-3-aroylindoles have affinity for the cannabinoid
      brain (CB(1)) receptor. This has led to the development of over 100
      cannabimimetic aminoalkylindoles, and the development of SAR for these compounds.
      Later work demonstrated that the aminoalkyl moiety was not necessary, and could
      be replaced by a four- to six-membered alkyl chain without loss of affinity.
      Investigation of these indoles led to the discovery of a CB(2) selective ligand,
      3-(1-naphthoyl)-N-propylindole. Subsequent work has provided several additional
      CB(2) selective indoles. On the basis of a proposed pharmacophore for the
      cannabimimetic indoles, a series of pyrroles and indenes were developed, some of
      which are potent cannabinoids. SAR for several series of pyrroles have been
      developed. Two groups have described cannabimimetic indenes, which have been
      employed as rigid models for the receptor interactions of cannabimimetic indoles
      with the CB(1) receptor. There is some evidence that the indoles bind to a
      somewhat different site on the receptor than traditional cannabinoids, and
      interact with the receptor primarily by aromatic stacking.

PMID- 15974992
TI  - Endocannabinoid-related enzymes as drug targets with special reference to N
      acylphosphatidylethanolamine-hydrolyzing phospholipase D.
AB  - Anandamide (N-arachidonoylethanolamine) is the first discovered endocannabinoid
      (endogenous ligand of cannabinoid receptors). In animal tissues, anandamide is
      principally formed together with other bioactive long-chain N-acylethanolamines
      from membrane glycerophospholipid by two enzyme reactions. The first reaction is
      the transfer of a fatty acyl chain from the sn-1 position of glycerophospholipid
      to phosphatidylethanolamine by calcium-dependent N-acyltransferase, resulting in
      the generation of N-acylphosphatidylethanolamine (NAPE). The second reaction is
      catalyzed by a phosphodiesterase of the phospholipase D (PLD)-type, which
      releases N-acylethanolamines from their corresponding NAPEs. The produced N
      acylethanolamines are hydrolyzed to fatty acids and ethanolamine by fatty acid
      amide hydrolase or an amidase acting exclusively at acidic pH. Our recent cDNA
      cloning of the NAPE-hydrolyzing PLD (NAPE-PLD) from mouse, rat and human revealed
      that NAPE-PLD is a novel enzyme which has no homology with any known PLD enzymes,
      but belongs to the zinc metallo-hydrolase family of the beta-lactamase fold. The
      recombinant enzyme hydrolyzed various NAPEs, including the anandamide precursor N
      arachidonoylphosphatidylethanolamine at similar rates, but was inactive with
      phosphatidylcholine and phosphatidylethanolamine. Considering cannabimimetic
      activities of anandamide, the enzymes involved in the biosynthesis and
      degradation of anandamide, including NAPE-PLD, may be promising targets for
      therapeutic agents.

PMID- 15974993
TI  - New medium oxacyclic O,N-acetals and related open analogues: biological
      activities.
AB  - Attention is increasingly being focussed on the cell cycle and apoptosis as
      potential targets for therapeutic intervention in cancer. Taking 1-[(2-oxepanyl)]
      5-fluorouracil previously prepared by us, we committed ourselves to increase the
      lipophilicity of this upper cyclohomologue of Ftorafur and prepared a series of
      bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against
      the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals
      or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in
      addition to six- and to 14-membered aminal structures and acyclic compounds. All
      the cyclic aminals provoked a G(o)/G(1)-phase cell cycle arrest, whereas
      Ftorafur, a known prodrug of 5-FU, and 1-[2-(2-hydroxymethyl-4-nitrophenoxy)-1
      methoxyethyl]-5-fluorouracil (51) induced an S-phase cell cycle arrest. Although
      breast cancer is most often treated with conventional cytotoxic agents it has
      proved difficult to induce apoptosis in breast cancer cells and, consequently,
      improved clinical responses may be obtained by identifying therapies that are
      particularly effective in activating apoptosis. 1-(2,3-Dihydrobenzoxepin-2-yl)-5
      fluorouracil (26) may be particularly useful in stimulating apoptosis in breast
      cancer. This compound is more potent as an apoptotic inductor than paclitaxel
      (Taxol). Finally, a fact that is worth emphasizing is that the cyclic and acyclic
      5-FU O,N-acetals induce neither toxicity nor death in mice after one month's
      treatment when administered intravenously twice a week, with a 50 mg/kg dose each
      time. Taken together, the experimental findings provide evidence of specific anti
      tumour activity of these new substances and warrant further evaluation in in vivo
      models of breast cancer to future clinical applications.

PMID- 15974994
TI  - Congestive heart failure: pharmacological agents and the potential of B-type
      natriuretic Peptide.
AB  - Congestive heart failure (CHF) is a life-threatening cardiovascular disease that
      is increasing in prevalence. It is a common cause of death and is accompanied by
      high direct and indirect costs for treatment. The current situation faced by
      patients and the medical community with regard to this ailment is one of high
      mortality, repeated hospitalizations, and combination therapies. The various
      classes of pharmacological agents that are currently used for patients suffering
      from CHF include angiotensin converting enzyme (ACE) inhibitors, angiotensin
      receptor blockers (ARBs), aldosterone antagonists, beta-blockers, calcium channel
      blockers (CCBs), digitalis drugs, diuretics, inotropic agents, nitrates, and
      vasodilators. While these agents are all important therapeutic tools in the
      treatment of CHF, the prognosis for patients with CHF remains poor. Thus
      improvement of the current pharmacological armamentarium is greatly needed. An
      endogenous peptide, B-type natriuretic peptide (BNP), has been increasingly
      utilized in the setting of acute CHF since its approval in 2001. This peptide, or
      a derivative thereof, has great potential for the treatment of patients at
      various stages in the progression of heart failure. This review provides an
      overview of current pharmacological strategies in CHF and addresses potential
      future developments in the use of BNP for the treatment of CHF.

PMID- 15974995
TI  - Dual antagonists of integrins.
AB  - The roles of integrins in pathologies have been studied intensively and only
      partially explained. This has resulted in the development of several nanomolar
      antagonists to certain integrins. In most cases, the aim was to produce compounds
      which are highly selective towards specific integrins. This paradigm has recently
      shifted a little. Targeting two or more integrins with one compound has become a
      very attractive concept, especially since it has become clear that several severe
      disorders, such as pathological angiogenesis, cannot be treated just with highly
      specific integrin antagonists. This review is aimed to elucidate some aspects
      regarding the design of drugs with dual activity towards integrins. Integrin
      structure and tissue distribution will first be described, in order to provide
      the basis for their functions in various pathologies which will follow.
      Inhibitors of several pairs of integrins will be described.

PMID- 15974996
TI  - Design and synthesis of protein superfamily-targeted chemical libraries for lead
      identification and optimization.
AB  - This review chronicles original literature dating back to 1992 outlining the
      applications of parallel synthesis and combinatorial chemistry to the synthesis
      of compound libraries focused towards specific superfamilies of molecular
      targets. Target families that have received significant literature coverage
      include kinases, proteases, nuclear hormone receptors and cell surface receptors,
      notably GPCRs.

PMID- 15974997
TI  - Overview of ribonucleotide reductase inhibitors: an appealing target in anti
      tumour therapy.
AB  - This review provides up-to-date information on the inhibition of ribonucleotide
      reductase (RNR), the enzyme that catalyses the reduction of ribonucleotides into
      deoxyribonucleotides. Taking in account that DNA replication and repair are
      essential mechanisms for cell integrity and are dependent on the availability of
      deoxyribonucleotides, many researchers are giving special attention to this
      enzyme, since it is an attractive target to treat several diseases of our time
      specially cancer. This investment has already given some benefits since some of
      these inhibitors show potent chemotherapeutic efficacy against a wide range of
      tumours such as non-small cell lung cancer, adenocarcinoma of pancreas, bladder
      cancer, leukaemia and some solid tumours. In fact a few of them have already been
      approved for the clinical treatment of some kinds of cancer. All aspects of RNR
      inhibition and corresponding inhibitors are the subjects of this review. The
      inhibitors are divided in three main groups: translation inhibitors, which unable
      the formation of the enzyme; dimerization inhibitors that prevent the
      complexation of the two RNR subunits (R1 and R2); and catalytic inhibitors that
      inactivate subunit R1 and/or subunit R2, leading to RNR inactivity. In this last
      group special focus will be addressed to substrate analogues.

PMID- 15974998
TI  - Labdanes of natural origin-biological activities (1981-2004).
AB  - Terpenoids is a class of natural compounds found in higher plants, mosses,
      liverworts, algae and lichens, as well as in insects, microbes or marine
      organisms. Through centuries many of these compounds have been used as
      ingredients of perfumes, drugs, narcotics or pigments. Labdanes, belonging to the
      bicyclic diterpenoids group, have been found as secondary metabolites in tissues
      of fungi, insects, marine organisms, and in essential oils, resins and tissues of
      higher plants. The diterpenes of labdane type, have been reported to have broad
      spectrum of biological activities. In this study, the reported bioactivities
      and/or uses of them, the last two decades (1981-2004), are selected as an attempt
      to underline their role in nature.

PMID- 15974999
TI  - Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine ligands, new tools to characterize
      A3 adenosine receptors in human tumor cell lines.
AB  - Increased concentrations of extracellular adenosine are reached in ischemic or
      inflamed tissues but have also been detected inside tumoral masses. If this
      finding may account for an important role of adenosine in the pathogenesis of
      tumors remains to be determined in view of its contradictory effects on cell
      survival and proliferation. In particular, adenosine was found to exert its
      effects on proliferation and on cell death mainly through the A(3) adenosine
      receptor. Therefore, a complete pharmacological characterization of the subtype
      and number of the expressed A(3) adenosine receptors is necessary for the
      elucidation of the role of adenosine via A(3) receptors in a specific cell
      subtype. The lack of potent and selective radiolabelled A(3) receptor antagonists
      has been, in the past, the major obstacle in the characterization of structure,
      function and regulation of this adenosine receptor subtype. Recently, our group
      has identified a series of substituted pyrazolotriazo-lopyrimidine derivatives as
      potent and selective antagonists to human A(3) adenosine receptors. The most
      recent results obtained in this field will be summarized in the present review.
      Furthermore, the review will report the results of the biochemical and
      pharmacological characterization of A(3) receptors in different human tumor cell
      lines and the multiple A(3) receptor-sustained ways that could prime tumor
      development.

PMID- 15975000
TI  - Renin-angiotensin system block and atrial fibrillation.
AB  - Atrial fibrillation is the most common disorder of cardiac rhythm. In spite of
      diagnosis simplicity, patients with atrial fibrillation are difficult to treat.
      In the recent years with the description of the phenomenon called remodelling, it
      has been possible to better define the principle mechanisms responsible for
      initiation, maintenance and, in some instances, termination of atrial
      fibrillation. Electrical, mechanical and anatomical remodelling indicate those
      alterations that, once established, may vanish any attempt to restore sinus
      rhythm. Atrial fibrosis is probably the most critical component of the
      remodelling process and appears to be largely mediated by the activation of the
      Renin-Angiotensin-Aldosterone System. Both experimental and clinical data have
      confirmed the pro-arrhythmic role of the Renin-Angiotensin-Aldosterone System and
      demonstrated an anti-arrhythmic effects of ACE-inhibitors and AT(1) receptor
      blockers. Regarding atrial fibrillation, it has been recently reported that the
      adjunction of AT(1) receptor blocker to amiodarone was more effective than the
      anti-arrhythmic drug alone, in reducing arrhythmia recurrence after electrical
      cardioversion. This and subsequent clinical observations indicate that
      pharmacological interventions capable of interfering with the electrical and
      structural remodelling process are of critical importance in the management of
      patients with atrial fibrillation. ACE inhibitors and AT(1) receptor blockers
      represent new and efficient therapeutical options to contrast the nearly
      inevitable progression of this arrhythmia towards its permanent form.

PMID- 15975001
TI  - Urinary steroid measurements in some endocrine and psychiatric diseases.
AB  - In 1990, the worldwide accepted Shackleton method, which provides a possibility
      of determining the steroid metabolites from urine, was adopted in our laboratory.
      The procedure is very useful in the diagnosis of different endocrine diseases and
      in the recognition of dysfunction or absence of enzymes with an important role in
      steroid metabolism, and it gives possibility to control the treatment in patients
      with these diseases. Besides the proximate clinical application, the method gives
      a convenient tool to study the steroid background of these disorders, helping us
      understand the mechanism of their development. In the last few years, we have
      examined the steroid profile of patients with hair (androgen alopecia /AA/,
      effluvium /E/), psychiatric problems (major depression /MD/, eating disorders
      /EDS/, especially anorexia nervosa and bulimia) and osteoporosis (OP). In all of
      the examined hair loss diseases, the levels of main androgen metabolites were
      increased, and elevated 5alpha-reductase activity were found. We could observe
      the alteration of the activity of 11beta-hydroxysteroid dehydrogenase (11beta
      HSD) enzyme and marked gender differences in the changes of the steroid
      metabolism in patients with major depression (MD). In women with OP, the
      significantly decreased level of certain metabolites points to the role of
      testosterone, androstenedione and DHEA in postmenopausal bone loss in women. Our
      experiences contribute to the knowledge of the nature and steroid background of
      some endocrine and psychiatric diseases.

PMID- 15975002
TI  - Novel agents that potentially inhibit irinotecan-induced diarrhea.
AB  - Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]
      carbonyloxycamptothecin) has exhibited clinical activities against a broad
      spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However,
      severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and
      severe diarrhea) hinder its clinical use. The latter consists of early and late
      onset diarrhea, occurring within 24 hr or > or = 24 hr after CPT-11
      administration, respectively. This review highlights novel agents potentially
      inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance
      of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea
      is observed immediately after CPT-11 infusion and probably due to the inhibition
      of acetylcholinesterase activity, which can be eliminated by administration of
      atropine. Late-onset diarrhea appears to be associated with intestinal exposure
      to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11,
      which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to
      the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and
      SN-38 may also stimulate the production of pro-inflammatory cytokines and
      prostaglandins (PGs), thus inducing the secretion of Na(+) and Cl(-). Early
      treatment of severe late-onset diarrhea with oral high-dose loperamide has
      decreased patient morbidity. Extensive studies have been conducted to identify
      other potential agents to ameliorate diarrhea in preclinical and clinical models.
      These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P
      glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor
      necrosis factor-alpha (TNF-alpha) inhibitors, or blockers of biliary excretion of
      SN-38. Further studies are needed to identify the molecular targets associated
      with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced
      diarrhea.

PMID- 15975004
TI  - Helper functions required for wild type and recombinant adeno-associated virus
      growth.
AB  - The human parvovirus Adeno-Associated virus (AAV-2) has been classified as a
      Dependovirus because it requires the presence of a helper virus to achieve a
      productive replication cycle. Several viruses such as Adenovirus (Ad), Herpes
      Simplex Virus (HSV), Vaccinia virus, and human papillomaviruses (HPV) can provide
      the helper activities required for AAV growth. The studies on the helper
      activities provided by adenovirus have provided useful information not only to
      understand the AAV-2 biology but also to develop tools for the production of
      recombinant AAV particles (rAAV). This review will focus on the current knowledge
      about the helper activities provided by the most extensively studied helper
      viruses, Ad and HSV-1, and also illustrate the methods used to supply the helper
      functions rAAV assembly.

PMID- 15975005
TI  - Mechanisms of adeno-associated virus genome encapsidation.
AB  - The defective parvovirus, adeno-associated virus (AAV), is under close scrutiny
      as a human gene therapy vector. AAV's non-pathogenic character, reliance on
      helper virus co-infection for replication and wide tissue tropism, make it an
      appealing vector system. The virus' simplicity and ability to generate high titer
      vector preparations have contributed to its wide spread use in the gene therapy
      community. The single stranded AAV DNA genome is encased in a 20-25 nm diameter,
      icosahedral protein capsid. Assembly of AAV occurs in two distinct phases. First,
      the three capsid proteins, VP1-3, are rapidly synthesized and assembled into an
      empty virion in the nucleus. In the second, rate-limiting phase, single-strand
      genomic DNA is inserted into pre-formed capsids. Our rudimentary knowledge of
      these two phases comes from radioactive labeling pulse-chase experiments,
      cellular fractionation and immunocytological analysis of infected cells. Although
      the overall pattern of virus assembly and encapsidation is known, the biochemical
      mechanisms involved in these processes are not understood. Elucidation of the
      processes of capsid assembly and encapsidation may lead to improved vector
      production. While all of the parvoviruses share the characteristic icosahedral
      particle, differences in their surface topologies dictate different receptor
      binding and tissue tropism. Based on the analysis of the molecular structures of
      the parvoviruses and capsid mutagenesis studies, investigators have manipulated
      the capsid to change tissue tropism and to target different cell types, thus
      expanding the targeting potential of AAV vectors.

PMID- 15975006
TI  - New recombinant serotypes of AAV vectors.
AB  - AAV based vectors can achieve stable gene transfer with minimal vector related
      toxicities. AAV serotype 2 (AAV2) is the first AAV that was vectored for gene
      transfer applications. However, the restricted tissue tropism of AAV and its low
      transduction efficiency have limited its further development as vector. Recent
      studies using vectors derived from alternative AAV serotypes such as AAV1, 4, 5
      and 6 have shown improved potency and broadened tropism of the AAV vector by
      packaging the same vector genome with different AAV capsids. In an attempt to
      search for potent AAV vectors with enhanced performance profiles, molecular
      techniques were employed for the detection and isolation of endogenous AAVs from
      a variety of human and non-human primate (NHP) tissues. A family of novel primate
      AAVs consisting of 110 non-redundant species of proviral sequences was discovered
      and turned to be prevalent in 18-19% of the tissues evaluated. Phylogenetic and
      functional analyses revealed that primate AAVs are segregated into clades based
      on phylogenetic relatedness. The members within a clade share functional and
      serological properties. Initial evaluation in mouse models of vectors based on
      these novel AAVs for tissue tropism and gene transfer potency led to the
      identification of some vector with improved gene transfer to different target
      tissues. Gene therapy treatment of several mouse and canine models with novel AAV
      vectors achieved long term phenotypic corrections. Vectors based on new primate
      AAVs could become the next generation of efficient gene transfer vehicles for
      various gene therapy applications.

PMID- 15975008
TI  - Adeno-associated viral vectors for clinical gene transfer studies.
AB  - Recombinant adeno-associated viral (rAAV) vectors can mediate the safe and long
      term correction of genetic diseases in animal models following a single
      administration. These pre-clinical studies are the basis of human trials that
      have shown rAAV vector persistence and safety in humans following delivery to
      lung, sinus, skeletal muscle, brain and liver. Transient disease correction has
      also been demonstrated in humans treated for hemophilia B and cystic fibrosis
      using AAV2 vectors. The physiochemical properties of rAAV vector virions are
      amenable to industry accepted manufacturing methodologies, long-term storage and
      direct in vivo administration. Recombinant adeno-associated virus vectors are
      manufactured in compliance with current Good Manufacturing Practices (cGMPs) as
      outlined in the Code of Federal Regulations (21CFR). To meet these requirements,
      manufacturing controls and quality systems are established, including 1) adequate
      facilities and equipment, 2) personnel who have relevant education or experience
      and are trained for specific assigned duties, 3) raw materials that are qualified
      for use and 4) a process (including production, purification, formulation,
      filling, storage and shipping) that is controlled, aseptic, reliable and
      consistent. Quality systems including Quality Control (QC) and Quality Assurance
      (QA) are also implemented. These manufacturing procedures and quality systems are
      designed so the product meets its release specifications to ensure that patients
      receive a safe, pure, potent and stable investigational drug.

PMID- 15975007
TI  - AAV hybrid serotypes: improved vectors for gene delivery.
AB  - In recent years, significant efforts have been made on studying and engineering
      adeno-associated virus (AAV) capsid, in order to increase efficiency in targeting
      specific cell types that are non-permissive to wild type (wt) viruses and to
      improve efficacy in infecting only the cell type of interest. With our previous
      knowledge of the viral properties of the naturally occurring serotypes and the
      elucidation of their capsid structures, we can now generate capsid mutants, or
      hybrid serotypes, by various methods and strategies. In this review, we summarize
      the studies performed on AAV retargeting, and categorize the available hybrid
      serotypes to date, based on the type of modification: 1) transcapsidation, 2)
      adsorption of bi-specific antibody to capsid surface, 3) mosaic capsid, and 4)
      chimeric capsid. Not only these hybrid serotypes could achieve high efficiency of
      gene delivery to a specific targeted cell type, which can be better-tailored for
      a particular clinical application, but also serve as a tool for studying AAV
      biology such as receptor binding, trafficking and genome delivery into the
      nucleus.

PMID- 15975009
TI  - Immune responses to adeno-associated virus vectors.
AB  - One of the biggest challenges in optimizing viral vectors for gene therapy
      relates to the immune response of the host. Adeno-associated virus (AAV) vectors
      are associated with low immunogenicity and toxicity, resulting in vector
      persistence and long-term transgene expression. The inability of AAV vectors to
      efficiently transduce or activate antigen presenting cells (APCs) may account for
      their decreased immunogenicity. AAV mediated gene therapy however, leads to the
      development of antibodies against the vector capsid. Anti-AAV antibodies have
      neutralizing effects that decrease the efficiency of in vivo gene therapy and can
      prevent vector re-administration. Furthermore, recent studies have shown that AAV
      vectors can elicit both cellular and humoral immune responses against the
      transgene product. Both cell-mediated response and humoral response to the
      delivered gene depend on a number of variables; including the nature of the
      transgene, the promoter used, the route and site of administration, vector dose
      and host factors. The response of the host to the vector, in terms of antigen
      specific immunity, will play a substantial role in clinical outcome. It is
      therefore important to understand both, why AAV vectors are able to escape
      immunity and the circumstances and mechanisms that lead to the induction of
      immune responses. This review will summarize innate and adaptive immune responses
      to AAV vectors, discuss possible mechanisms and outline strategies, such as
      capsid modifications, use of alternative serotypes, or immunosuppression, which
      have been used to circumvent them.

PMID- 15975010
TI  - Adeno-associated virus (AAV) vectors in the CNS.
AB  - Adeno-associated virus (AAV) vectors exhibit a number of properties that have
      made this vector system an excellent choice for both CNS gene therapy and basic
      neurobiological investigations. In vivo, the preponderance of AAV vector
      transduction occurs in neurons where it is possible to obtain long-term, stable
      gene expression with very little accompanying toxicity. Promoter selection,
      however, significantly influences the pattern and longevity of neuronal
      transduction distinct from the tropism inherent to AAV vectors. AAV vectors have
      successfully manipulated CNS function using a wide variety of approaches
      including expression of foreign genes, expression of endogenous genes, expression
      of antisense RNA and expression of RNAi. With the discovery and characterization
      of different AAV serotypes, the potential patterns of in vivo vector transduction
      have been expanded substantially, offering alternatives to the more studied AAV 2
      serotype. Furthermore, the development of specific AAV chimeras offers the
      potential to further refine targeting strategies. These different AAV serotypes
      also provide a solution to the immune silencing that proves to be a realistic
      likelihood given broad exposure of the human population to the AAV 2 serotype.
      These advantageous CNS properties of AAV vectors have fostered a wide range of
      clinically relevant applications including Parkinson's disease, lysosomal storage
      diseases, Canavan's disease, epilepsy, Huntington's disease and ALS. Each
      individual application, however, presents a unique set of challenges that must be
      solved in order to attain clinically effective gene therapies.

PMID- 15975011
TI  - Adeno-associated viral vectors for retinal gene transfer and treatment of retinal
      diseases.
AB  - Retinal gene transfer holds big promises for the treatment of inherited and non
      inherited blinding diseases, such as retinitis pigmentosa or age-related macular
      degeneration. Key to the development of successful gene-based therapies for the
      eye are efficient tools for retinal gene transfer. Vectors based on adeno
      associated viruses (AAV) are able to transduce robustly and persistently
      different retinal cell types of animal models after a single intraocular
      administration. Recombinant AAV (rAAV) vectors are versatile gene transfer tools
      in that capsid proteins from dozens of AAV serotypes can be easily interchanged,
      resulting in the creation of recombinant vectors with unique transduction
      properties. This has allowed successful proof-of-principle studies using rAAV
      mediated gene transfer to restore retinal morphology and function in small and
      large animal models of retinal diseases. In addition, gene delivery using rAAV
      vectors in the eye seems to have appropriate biosafety characteristics to rapidly
      move it from bench to bedside. All the above aspects will be reviewed and
      discussed in detail below.

PMID- 15975012
TI  - AAV-mediated gene transfer for treatment of hemophilia.
AB  - Adeno-associated viral (AAV) gene transfer of coagulation factor VIII and IX to
      skeletal muscle and liver of murine and canine models of hemophilia A and B have
      resulted in sustained systemic expression and, in several studies, in complete
      cure of the bleeding disorder. These impressive results prompted initiation of
      two Phase I/II clinical trials to evaluate the safety of AAV-factor IX gene
      transfer to muscle and liver of patients with severe hemophilia B. Herein, we
      have reviewed results from studies in animals with hemophilia, early experience
      with the vector system in the clinic, recent innovative approaches in vector
      design and delivery, and strategies to circumvent immunological limitations.
      Taken together, these studies provide much encouragement for the possibility of
      future clinical success, but also point out hurdles that still have to be
      overcome.

PMID- 15975013
TI  - Recent developments in recombinant AAV-mediated gene therapy for lung diseases.
AB  - Recent studies have shed light on a number of important obstacles to safe and
      effective gene transfer to the respiratory tract with recombinant AAV vectors.
      Among these are blocks at the level of receptor binding and internalizations,
      evasion of proteasomal degradation, inefficiency of nuclear entry, and nuclear
      factors that inhibit the conversion of rAAV genomes into active double-stranded
      DNA form. Other important issues have been the size constraints of the vector,
      the lack of retention of episomal forms of the vector genome, and immune
      responses which may limit the efficiency of repeated doses of rAAV. Each of these
      potential obstacles has been addressed with new vector designs. In addition, the
      availability of an abundance of novel rAAV serotypes, each with its own receptor
      tropism, has expanded the range of possibilities for long-term success of gene
      therapy in the respiratory tract.

PMID- 15975014
TI  - HIV vaccine discovery and development.

PMID- 15975015
TI  - Fundamental immunology and what it can teach us about HIV vaccine development.
AB  - This survey covers the immunological background to development of an HIV vaccine,
      starting from an overview of present understanding of the mechanisms of
      immunoregulation. It follows the uptake, processing and presentation of an
      antigen, from its initial uptake by a dendritic cell and its deposit on the
      dendrites of follicular dendritic cells. It pursues the antigen through uptake by
      B cells, presentation of epitopes to helper T cells and the eventual production
      of antibody. In the second arm of the immune response it follows synapse
      formation between dendritic cell and CD4/CD8 cells leading to production of CTL.
      It identifies epitope linkage as a key element in directing these pathways. It
      identifies the principal functions of the various types of cell cooperation.
      Continuing, it focuses on topics relevant to vaccine development: Th1/Th2
      balance: new adjuvants based on ligands of TLRs and other activators of innate
      immunity, as well as new forms of intervention in antigen processing. We urge
      that the new vaccine fusion constructs be evaluated against a fusion gold
      standard rather than against antigen alone. These considerations open new
      strategies of HIV vaccine development. . Finally we urge that vaccine trials
      should include storage of individual DNA samples, in order to gain better
      understanding of the genetic parameters of vaccine efficacy.

PMID- 15975016
TI  - Antibodies: can they protect against HIV infection?
AB  - More than 20 million people have died since the discovery of human
      immunodeficiency virus (HIV), yet a broadly reactive AIDS vaccine remains
      elusive. Neutralizing antibody (nAb) response-based vaccine strategies were the
      first to be tested; however, when the difficulty in neutralizing primary HIV
      isolates was recognized, vaccine development focused instead on generating
      cytotoxic T-lymphocyte (CTL) responses. Recently, interest in anti-HIV nAbs has
      been revived by the impressive protection achieved in primates given passive
      immunization with neutralizing monoclonal antibodies (nmAbs) isolated from HIV
      clade B-infected individuals. The nmAbs used in these studies target conserved,
      functionally important epitopes in HIV gp120 and gp41. Regimens involving
      combinations of such human nmAbs or high-dose single-agent nmAb protected monkeys
      against intravenous (iv) and mucosal challenges with simian-human
      immunodeficiency virus (SHIV) strains encoding X4, X4R5 or R5 HIV env genes. In
      several such studies, sterilizing immunity was achieved, thus providing proof-of
      concept that nAbs targeting conserved epitopes can be fully protective. The
      existence of these broadly reactive nmAbs suggests that it may be possible to
      design immunogens capable of inducing similar nAb responses by active
      vaccination. Unraveling the three-dimensional structures involved in the nmAb-HIV
      Env epitope interactions may facilitate the future development of a potent AIDS
      vaccine. This review is focused on the importance of nAbs in protecting against
      HIV infection or in containing viral spread, with particular emphasis on the
      successful use of nmAbs in passive immunization studies. The implications of the
      data from these studies on AIDS vaccine design in general are also discussed.

PMID- 15975017
TI  - CD8+ T-cells: are they sufficient to prevent, contain or eradicate HIV-1
      infection?
AB  - The prevention of HIV-1 by vaccination has proven to be a formidable task. In an
      ongoing endeavor to end the HIV-1 pandemic, scientists seek vaccines that will
      elicit quantitatively and qualitatively robust B-cell and T-cell activities.
      Given that cytotoxic T-lymphocytes (CTL) play a substantial role in the
      immunological control of immunodeficiency virus infections, this review will
      focus on vaccines designed to elicit HIV-1-specific CTL. Vaccine approaches using
      various HIV-1 proteins or specific CTL determinants, partnered with diverse
      delivery systems and adjuvants will be discussed. Lessons from studies with other
      virus models (e.g. gamma herpes virus and influenza virus) will also be examined.
      Since CTL contribute to the success of vaccines in other model systems, an
      understanding of the strengths and possible limitations of these cells may be
      critical to future successes in the HIV-1 vaccine field.

PMID- 15975018
TI  - Differentiation of CD8 T cells in response to acute and chronic viral infections:
      implications for HIV vaccine development.
AB  - Successful HIV vaccine strategies will likely require the induction of robust
      cellular immune responses, in addition to strong humoral responses.
      Unfortunately, there is no clear molecular definition of an effective HIV
      specific CD8 T cell response. In this review, we discuss the differentiation of
      CD8 T cells in response to acute and chronic viral infections. We then apply
      concepts derived from these studies to predict the desirable characteristics of
      HIV-specific CD8 T cell memory.

PMID- 15975019
TI  - Inactivated- or killed-virus HIV/AIDS vaccines.
AB  - Inactivated or "killed" virus (KV) is a "classical" approach that has produced
      safe and effective human and veterinary vaccines but has received relatively
      little attention in the effort to develop an HIV/AIDS vaccine. Initially, KV and
      rgp120 subunit vaccines were the two most obvious approaches but, unfortunately,
      rgp120 has not been efficacious and the KV approach has been limited by a variety
      of scientific, technical, and sociological factors. For example, when responses
      to cellular antigens, present on SIV grown in human cells, proved to be largely
      responsible for efficacy, the KV approach was widely discounted. Similarly, when
      lab-adapted HIV-1 appeared to lose envelope glycoprotein during preparation (not
      the case for primary isolates), this was viewed as a fundamental barrier to the
      KV concept. Also, a preference for "safer", genetically-engineered vaccines, and
      emphasis on cellular immunity, have left KV low on the priority list for funding
      agencies and investigators. The recent suggestion that "native" trimeric gp120
      displays conserved conformational neutralization epitopes, along with the failure
      of rgp120, and difficulties in raising strong cellular responses with DNA or
      vectored vaccines, has restored some interest in the KV concept. In the past 15
      years, several groups have initiated pre-clinical development of KV candidates
      for SIV or HIV and promising, albeit limited, information has been produced. In
      this chapter we discuss the rationale (including pros and cons) for producing and
      testing killed-HIV vaccines, the prospects for success, the nature and scope of
      research needed to test the KV concept, what has been learned to date, and what
      remains undone.

PMID- 15975020
TI  - Application of the polyvalent approach to HIV-1 vaccine development.
AB  - One major obstacle to the design of a global HIV-1 vaccine is viral diversity.
      Presently, data suggest that a single antigen will not suffice to generate
      broadly reactive neutralizing antibodies to protect all individuals against all
      subtypes of HIV-1 infection. While some of the neutralizing epitopes are
      identified in the constant regions of the HIV-1 envelope (Env) glycoprotein, many
      are localized to variable regions and differ conformationally from one virus to
      the next. The successes of polyvalent vaccine approaches against other
      antigenically variable pathogens encourage adoption of the same approach for HIV
      1 vaccine design. The critical question is which envelope antigens should be
      combined in a vaccine cocktail to provide maximum protection against HIV-1. A
      review of the existing human vaccines based on the polyvalent principle is
      included here to provide a historical perspective for the current effort of
      developing a polyvalent HIV-1 vaccine. Data generated from several groups
      actively working on candidate polyvalent HIV-1 vaccines are summarized.
      Information presented in this review highlights the potential and importance of
      the polyvalent vaccine approach for the future development of an effective HIV-1
      vaccine.

PMID- 15975021
TI  - HIV-1: the confounding variables of virus neutralization.
AB  - The development of an effective vaccine against HIV-1 would be greatly
      facilitated by the ability to elicit potent, high affinity antibodies that are
      capable of broad neutralization, viral inactivation and protection against
      infection and/or disease. New insights into the structure and function of the HIV
      1 envelope glycoprotein (Env) that mediates viral fusion and entry may ultimately
      lead to strategies successful in eliciting these protective antibody responses.
      Insights have been gained regarding HIV-1 Env attachment and receptor engagement,
      the fusion process and kinetics, and the structural/functional attributes of Env
      that allow humoral immune evasion. In addition, studies of a limited number of
      broadly neutralizing human monoclonal antibodies have shed some light as to how
      antibodies may penetrate the immune evading armor that HIV-1 has evolved. As the
      elusive goal of generating these types of antibodies emerge and are developed in
      the context of generating new candidate HIV-1 vaccines, a relevant in vitro
      measurement of neutralization by these types of antibodies becomes a complex
      task. This is in part due to a list of confounding variables which include: the
      physical and genomic nature (amino acid variation) of the infecting virion, the
      type of target cells, the concentration and clonality of the reactants, assay
      format and design, the affinity and kinetics of the reaction,
      receptors/coreceptors and attachment factors, and soluble host factors. This
      review will focus on the past, current, and future knowledge required to advance
      the field of HIV-1 humoral immunity as it impacts future HIV-1 vaccine
      development.

PMID- 15975022
TI  - HIV-1 envelope evolution and vaccine efficacy.
AB  - Transmission of human immunodeficiency virus type 1 (HIV-1) selects for envelope
      variants with a number of defined properties, including use of CCR5 as the
      preferred coreceptor, binding to CCR5 in a distinct manner compared to HIV-1
      isolated later in infection, shorter variable (V) regions, and fewer N-linked
      glycosylation sites. These features define the ideal target for an envelope
      containing vaccine designed to elicit neutralizing antibody. If a candidate
      vaccine were sufficiently potent to elicit sterilizing immunity, virus evolution
      would not be an issue. However, all results to date suggest that an envelope
      containing vaccine will have a lesser impact, and that virus evolution will
      contribute to escape from the vaccine-induced antibody response. The key question
      is whether or not the early selection pressure imposed by neutralizing antibody
      will have a long term impact on HIV disease progression. Several recent reports
      suggest that HIV-1 will evolve to rapidly escape antibody selection, and that the
      cost to the virus in terms of entry fitness will be small. Durable effects of
      vaccination are predicted to be associated with a reduction in peak viremia and
      viral set point at the time of primary infection.

PMID- 15975023
TI  - Predicting the potential public health impact of disease-modifying HIV vaccines
      in South Africa: the problem of subtypes.
AB  - Current HIV vaccines in development appear unlikely to prevent infection, but
      could provide benefits by increasing survival; such vaccines are described as
      disease-modifying vaccines. We review the current status of vaccines and modeling
      vaccines. We also predict the impact that disease-modifying vaccines could have
      in South Africa, where multiple subtypes are co-circulating. We model
      transmissibility/fitness differences among subtypes. We used uncertainty analyses
      to model vaccines with four characteristics: (i) take, (ii) duration of immunity,
      (iii) reduction in transmissibility/fitness, and (iv) increase in survival. We
      reconstructed, and forecasted, the South African epidemic from 1940 to 2140
      (assuming no vaccination). We predict that: (i) incidence will peak in 2014,
      decline, and stabilize, (ii) prevalence will continue to rise, and (iii) the AIDS
      death rate curve will peak in 2022. Our predictions show that (over the next 135
      years) the epidemic in South Africa will switch from a predominantly Subtype C
      epidemic to an epidemic driven by other subtypes. We predict that the epidemic
      could remain unchanged, even with mass vaccination with a vaccine that is equally
      effective against all co-circulating subtypes. However, if the non-C subtypes are
      less (or equally) transmissible as Subtype C then disease-modifying vaccines
      could result in eradication. Thus, in countries where multiple-subtypes are co
      circulating it is critical to realize that small biological differences among
      subtypes will have dramatic consequences for the effectiveness of HIV vaccination
      campaigns. A slight difference in fitness will determine whether a disease
      modifying vaccine has almost no impact on the epidemic or can achieve
      eradication.

PMID- 15975026
TI  - The neuroinflammatory response in plaques and amyloid angiopathy in Alzheimer's
      disease: therapeutic implications.
AB  - The amyloid plaques in Alzheimer's disease (AD) brains are co-localised with a
      broad variety of inflammation-related proteins (complement proteins, acute-phase
      proteins, pro-inflammatory cytokines) and clusters of activated microglia. The
      present data suggest that the Abeta depositions in the neuroparenchyma are
      closely associated with a locally-induced, non-immune-mediated chronic
      inflammatory response. Clinicopathological and neuroradiological data show that
      activation of microglia are a relatively early pathogenic event that precedes the
      process of severe neuropil destruction in patients. Recent gene findings (cDNA
      microarray) confirm the immunohistochemical findings of an early involvement of
      inflammatory and regenerative pathways in AD pathogenesis. Abeta deposition,
      inflammation and regenerative mechanisms are also early pathogenic events in
      transgenic mice models harbouring the pathological AD mutations, while "later"
      neurodegenerative characteristics are not seen in these models. Next to the
      plaques, Abeta amyloid deposition is frequently found in the walls of cerebral
      vessels (cerebral amyloid angiopathy). Most common is the type of amyloid
      deposition in the walls of meningeal and medium-sized cortical arteries, and more
      rarely, microcapillary amyloid angiopathy (dyshoric angiopathy).
      Immunohistochemical studies show that in AD patients, the majority of the amyloid
      deposits in the walls of the larger vessels is not associated with a chronic
      inflammatory response in contrast to micro-capillary amyloid angiopathy. In this
      contribution, we will give an overview of the similarities and differences
      between the involvement of inflammatory mechanisms in vascular and plaque amyloid
      in AD and transgenic models. The implications of the reviewed studies for an
      inflammation-based therapeutical approach in AD will be discussed.

PMID- 15975027
TI  - Amyloid associated proteins in Alzheimer's and prion disease.
AB  - Clustering of activated microglia in Abeta deposits is related to accumulation of
      amyloid associated factors and precedes the neurodegenerative changes in AD.
      Microglia-derived pro-inflammatory cytokines are suggested to be the driving
      force in AD pathology. Inflammation-related proteins, including complement
      factors, acute-phase proteins, pro-inflammatory cytokines, that normally are
      locally produced at low levels, are increasingly synthesized in Alzheimer's
      disease (AD) brain. Similar to AD, in prion diseases (Creutzfeldt-Jakob disease,
      Gerstmann-Straussler-Scheinker disease and experimentally scrapie infected mouse
      brain) amyloid associated factors and activated glial cells accumulate in amyloid
      deposits of conformational changed prion protein (PrPres). Biological properties
      of Abeta and prion (PrP) peptides, including their potential to activate
      microglia, relate to Abeta and PrP peptide fibrillogenic abilities that are
      influenced by certain amyloid associated factors. However, since small oligomers
      of amyloid forming peptides are more toxic to neurons than large fibrils, certain
      amyloid associated factors that enhance fibril formation, may sequester the
      potentially harmful Abeta and PrP peptides from the neuronal microenvironment. In
      this review the positive and negative actions of amyloid associated factors on
      amyloid peptide fibril formation and on the fibrillation state related activation
      of microglia will be discussed. Insight in these mechanisms will enable the
      design of specific therapies to prevent neurodegenerative diseases in which
      amyloid accumulation and glial activation are prominent early features.

PMID- 15975024
TI  - Non-human primate models for AIDS vaccine research.
AB  - Since the discovery of simian immunodeficiency viruses (SIV) causing AIDS-like
      diseases in Asian macaques, non-human primates (NHP) have played an important
      role in AIDS vaccine research. A multitude of vaccines and immunization
      approaches have been evaluated, including live attenuated viruses, DNA vaccines,
      viral and bacterial vectors, subunit proteins, and combinations thereof.
      Depending on the particular vaccine and model used, varying degrees of protection
      have been achieved, including prevention of infection, reduction of viral load,
      and amelioration of disease. In a few instances, potential safety concerns and
      vaccine-enhanced pathogenicity have also been noted. In the past decade,
      sophisticated methodologies have been developed to define the mechanisms of
      protective immunity. However, a clear road map for HIV vaccine development has
      yet to emerge. This is in part because of the intrinsic nature of the surrogate
      model and in part because of the improbability of any single model to fully
      capture the complex interactions of natural HIV infection in humans. The lack of
      standardization, the limited models available, and the incomplete understanding
      of the immunobiology of NHP contribute to the difficulty to extrapolate findings
      from such models to HIV vaccine development. Until efficacy data become available
      from studies of parallel vaccine concepts in humans and macaques, the predictive
      value of any NHP model remains unknown. Towards this end, greater appreciation of
      the utility and limitations of the NHP model and further developments to better
      mimic HIV infection in humans will likely help inform future AIDS vaccine
      efforts.

PMID- 15975028
TI  - Preventing activation of receptor for advanced glycation endproducts in
      Alzheimer's disease.
AB  - Receptor for advanced glycation endproducts (RAGE), a member of the
      immunoglobulin superfamily, is a multi-ligand, cell surface receptor expressed by
      neurons, microglia, astrocytes, cerebral endothelial cells, pericytes, and smooth
      muscle cells. At least three major types of the RAGE isoforms (full length, C
      truncated, and N-truncated) are present in human brains as a result of
      alternative splicing. Differential expression of each isoform may play a
      regulatory role in the physiological and pathophysiological functions of RAGE.
      Analysis of RAGE expression in non-demented and Alzheimer's disease (AD) brains
      indicated that increases in RAGE protein and percentage of RAGE-expressing
      microglia paralleled the severity of disease. Ligands for RAGE in AD include
      amyloid beta peptide (Abeta), S100/calgranulins, advanced glycation endproduct
      modified proteins, and amphoterin. Collective evidence from in vitro and in vivo
      studies supports that RAGE plays multiple roles in the pathogenesis of AD. The
      major features of RAGE activation in contributing to AD result from its
      interaction with Abeta, from the positive feedback mechanisms driven by excess
      amounts of Abeta, and combined with sustained elevated RAGE expression. The
      adverse consequences of RAGE interaction with Abeta include perturbation of
      neuronal properties and functions, amplification of glial inflammatory responses,
      elevation of oxidative stress and amyloidosis, increased Abeta influx at the
      blood brain barrier and vascular dysfunction, and induction of autoantibodies. In
      this article, we will review recent advances of RAGE and RAGE activation based on
      findings from cell cultures, animal models, and human brains. The potential for
      targeting RAGE mechanisms as therapeutic strategies for AD will be discussed.

PMID- 15975029
TI  - The Nrf2-ARE Signalling pathway: promising drug target to combat oxidative stress
      in neurodegenerative disorders.
AB  - A large body of evidence indicates that oxidative stress is a salient
      pathological feature in many neurodegenerative diseases, including Amyotrophic
      lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In addition to
      signs of systemic oxidative stress, at the biochemical and neuropathological
      level, neuronal degeneration in these disorders has been shown to coincide with
      several markers of oxidative damage to lipids, nucleic acids, and proteins in
      affected brain regions. Neuroinflammatory processes, often associated with the
      induction of free radical generating enzymes and the accumulation of reactive
      astrocytes and microglial cells, are considered as a major source of oxidative
      stress. Given the pathogenic impact of oxidative stress and neuroinflammation,
      therapeutic strategies aimed to blunt these processes are considered an effective
      way to confer neuroprotection. Recently, the nuclear transcription factor Nrf2,
      that binds to the antioxidant response element (ARE) in gene promoters, has been
      reported to constitute a key regulatory factor in the co-ordinate induction of a
      battery of endogenous cytoprotective genes, including those encoding for both
      antioxidant- and anti-inflammatory proteins. In the present review, besides
      discussing recent evidence underscoring the thesis that the Nrf2-ARE signalling
      pathway is an attractive therapeutic target for neurodegenerative diseases, we
      advocate the view that chemopreventive agents might be suitable candidates to
      serve as lead compounds for the development of a new class of neuroprotective
      drugs.

PMID- 15975030
TI  - Protein quality control in Alzheimer's disease: a fatal saviour.
AB  - Aggregation of Abeta plays a key role in the pathogenesis of Alzheimer's disease.
      Although the highly structured Abeta aggregates (fibrils) have long been thought
      to be the toxic form of Abeta, recent evidence suggests that smaller, soluble
      intermediates in Abeta aggregation are the real culprit. Because these oligomeric
      aggregates are already formed in the secretory pathway, this raises another
      issue: Is intra- or extracellular Abeta involved in the pathogenic cascade?
      Because aggregated proteins are very toxic, cells have developed quality control
      responses to deal with such proteins. A prime site for quality culum. Here,
      aberrant proteins are recognized and can be targeted for degradation to the
      cytosolic quality control system. In addition, there is accumulating evidence for
      quality control in other subcellular compartments in the cell. All quality
      control mechanisms are initially protective, but will become destructive after
      prolonged accumulation of aggregated proteins. This is enhanced by decreased
      efficiency of these systems during aging and therefore, these responses may play
      an important role in the pathogenesis of Alzheimer's disease. In this review, we
      will discuss the role of protein quality control in the neurotoxicity of Abeta.

PMID- 15975031
TI  - The expression of cell cycle proteins in neurons and its relevance for
      Alzheimer's disease.
AB  - Alzheimer's disease is a chronic neurodegenerative disorder characterised by
      typical pathological hallmarks such as amyloid deposition, neurofibrillary
      tangles and disturbances in the expression of various cell cycle proteins. A
      current pathogenetic hypothesis suggests that neurons, forced by external and
      internal factors, leave the differentiated G(0) phase and re-enter the cell
      cycle. This process results in neuronal de-differentiation and apoptosis and
      might contribute to an increased phosphorylation of the tau protein. There are a
      number of reports, however, describing the expression of cell cycle proteins in
      rodent or human brain under normal non-disease conditions. This might indicate
      that cell cycle expression of proteins in neurons is of physiological rather than
      pathophysiological relevance. Therefore, it needs to be carefully analysed
      whether the expression of cell cycle regulators such as cyclin-dependent kinases,
      cyclins or cyclin-dependent kinase inhibitors in neurons is a pathological
      hallmark that allows to discriminate between normal and disease condition. Here
      we attempt to summarise recent evidence for a dysfunction of cell cycle
      regulators in Alzheimer's disease, considering the potential functions of these
      molecules beyond cell cycle regulation.

PMID- 15975032
TI  - The role of COX-1 and COX-2 in Alzheimer's disease pathology and the therapeutic
      potentials of non-steroidal anti-inflammatory drugs.
AB  - Epidemiological studies indicate that anti-inflammatory drugs, especially the non
      steroidal anti-inflammatory drugs (NSAIDs), decrease the risk of developing
      Alzheimer's disease (AD). Their beneficial effects may be due to interference of
      the chronic inflammatory reaction in AD. The best-characterised action of NSAIDs
      is the inhibition of cyclooxygenase (COX). So far, clinical trials designed to
      inhibit inflammation or cyclooxygenase activity have failed in the treatment of
      AD patients. In this review we will focus on the role, expression and regulation
      of COX-1 and COX-2 in neurodegeneration and AD pathogenesis. Understanding the
      pathological, physiological and neuroprotective role of cyclooxygenase will
      contribute to the development of a therapy for the treatment or prevention of AD.

PMID- 15975035
TI  - Modulating alloimmune responses with plasmapheresis and IVIG.
AB  - Antibody-mediated barriers to renal transplantation, including donor specific
      anti-HLA and anti-blood group antibodies, have become an increasingly important
      issue over the last forty years as the organ shortage has continued to expand.
      The inevitable result of the unmet demand for compatible organs has been a
      continuous increase in recipient waiting times. Over the last decade, two
      treatment strategies have been developed to address this problem. These regimens
      rely on the immunomodulatory properties of intravenous immunoglobulin (IVIG)
      administered alone at relatively high doses, or at lower doses in combination
      with the non-selective depletion of antibodies from plasmapheresis. Both
      protocols have been successfully used for desensitization of patients with donor
      specific anti-HLA antibody and have allowed for renal transplantation with
      excellent outcomes. The combined strategy of plasmapheresis/IVIG has also been
      successfully employed for renal transplantation in recipients of ABO blood group
      incompatible kidneys. This review will provide an overview of these therapies and
      their application to incompatible renal transplantation.

PMID- 15975034
TI  - Pathological features of antibody-mediated rejection.
AB  - Although cell-mediated rejection has remained the most common form of graft
      rejection after organ transplantation, antibody-mediated rejection has recently
      gained much significance in clinical transplantation. New evidence points to an
      antibody-mediated rejection contributing not only to hyperacute and acute but
      also to chronic allograft rejection. In addition, in discordant
      xenotransplantation, severe forms of antibody-mediated rejection, including
      hyperacute rejection and acute humoral xenograft rejection, represent major
      immunological barriers to successful xenotransplantation. Antibody-mediated
      rejection in both allotransplantation and xenotransplantation typically does not
      respond to conventional anti-rejection therapy, so it has recently been
      recognized as a major cause of graft loss. Histopathology remains the most
      definitive and reliable tool for the diagnosis of graft rejection in both
      allografts and xenografts. In this review, we discuss the concept that
      microvascular injury is a characteristic feature of antibody-mediated rejection
      that develops in hyperacute, acute and chronic antibody-mediated rejection in
      both allografts and discordant xenografts as well as in kidney and heart grafts.
      We also review work indicating that endothelial cell activation and endothelial
      cell death in the microvasculature can contribute to ultimate graft loss by
      triggering capillary destruction, interstitial hemorrhage, and platelet-rich
      microthrombi in hyperacute and acute antibody-mediated rejection as well as with
      the formation and progression of fibrotic scars in chronic antibody-mediated
      rejection.

PMID- 15975036
TI  - Targeting antibody-mediated rejection in the setting of ABO-incompatible infant
      heart transplantation: graft accommodation vs. B cell tolerance.
AB  - In order for ABO-incompatible organ transplantation to be performed successfully,
      the antibody response must be targeted. Aggressive strategies are usually
      required both to remove pre-existing antibodies directed at donor A/B antigens
      and to suppress further production of antibodies. If this can be accomplished in
      the short-term, graft accommodation of ABO-incompatible transplants may develop
      upon eventual re-accumulation of antibodies as the graft acquires resistance to
      antibody-mediated damage. In contrast to mature individuals, very young infants
      lack isohemagglutinins due to a natural lag in development of immunity to T cell
      independent polysaccharide antigens. This delay in maturation permits a window of
      safety during which infants can receive ABO-incompatible grafts without the
      requirement for aggressive immunosuppressive strategies. We have recently
      demonstrated that ABO-incompatible heart transplantation performed during this
      stage of immaturity is followed by the spontaneous development of donor-specific
      B cell tolerance rather than graft accommodation, and that tolerance in this
      setting occurs by a cellular mechanism of antigen-specific B cell elimination.
      This finding is strikingly similar to the original descriptions of neonatal T
      cell tolerance in mice. Our data provide compelling justification that every
      effort should be made to include juvenile recipients routinely as subjects in
      tolerance research. Through understanding the mechanisms underlying tolerance in
      this setting, as with murine models of neonatal tolerance originally described by
      Medawar and colleagues, it may be possible to expand the potential applications
      of tolerance strategies to older patient populations.

PMID- 15975037
TI  - Antibody mediated rejection in pig-to-nonhuman primate xenotransplantation
      models.
AB  - Antibody-mediated mechanisms are central to the rejection that occurs when pig
      organs are transplanted into primates. In this article, the histopathological
      features of the humoral rejection process in these species combinations, namely
      hyperacute rejection and acute humoral xenograft rejection, will be illustrated.
      The profile of the natural and elicited antibodies involved will also be
      discussed. It has now been demonstrated that the natural immune response to a
      porcine xenograft is primarily directed to Galalpha1-3Gal (alphaGal)
      specificities, whilst the elicited immune response is directed to both alphaGal
      and non-alphaGal antigens. The principal characteristics of anti-alphaGal, anti
      non-alphaGal and polyreactive antibodies will be described, together with the
      identification of the molecules recognised by natural and elicited xenoreactive
      antibodies. The role of the humoral immune response in the rejection of porcine
      islets in the primate is still uncertain and the current views on the subject
      will be discussed. Finally, a concise but comprehensive review of the different
      strategies that have been attempted to prevent the onset of antibody-mediated
      rejection is presented. These strategies encompass approaches aimed at
      interfering with the binding of xenoreactive antibodies with their targets, the
      use of conventional or novel immunosuppressants and splenectomy. It is undeniable
      that significant progress has been recently achieved in understanding the humoral
      rejection process of pig organs transplanted into primates. It is expected that a
      more comprehensive elucidation of the mechanisms underlying accommodation and
      tolerance may, in the not too distant future, further extend survival of pig
      organs transplanted into primates.

PMID- 15975038
TI  - Beyond antibody-mediated rejection: hyperacute lung rejection as a paradigm for
      dysregulated inflammation.
AB  - The use of animal organs for transplantation in humans is seen as a potential
      solution to the short supply of human donor organs available for clinical
      transplantation. However, to develop this therapeutic option as clinical reality
      will require surmounting formidable obstacles. The primary immunologic barrier to
      pig-to-human xenotransplantation is hyperacute rejection (HAR), a phenomenon
      previously characterized as resulting from antibody binding and complement
      activation. This article will first review recent progress in the development of
      specific strategies to overcome hyperacute lung rejection (HALR), through
      production of genetically engineered pig organs, modification of the host innate
      immunity and control of antibody and complement. Additional therapeutic targets
      identified in HALR are reviewed, with particular emphasis on recent studies
      describing a critical role for the coagulation cascade in HAR.

PMID- 15975039
TI  - B cell tolerance: lessons from transplantation.
AB  - Given the ability of the B cell compartment to acquire tolerance to self we
      cannot explain why spontaneous humoral tolerance does not arise following
      transplantation. Here we review the fundamental mechanisms of B cell tolerance
      that operate in development and direct the reader to possible mechanisms that may
      explain how B cell tolerance fails to develop following transplantation.

PMID- 15975040
TI  - A comprehensive listing of bioactivation pathways of organic functional groups.
AB  - The occurrence of idiosyncratic adverse drug reactions during late clinical
      trials or after a drug has been released can lead to a severe restriction in its
      use and even in its withdrawal. Metabolic activation of relatively inert
      functional groups to reactive electrophilic intermediates is considered to be an
      obligatory event in the etiology of many drug-induced adverse reactions.
      Therefore, a thorough examination of the biochemical reactivity of functional
      groups/structural motifs in all new drug candidates is essential from a safety
      standpoint. A major theme attempted in this review is the comprehensive
      cataloging of all of the known bioactivation pathways of functional groups or
      structural motifs commonly utilized in drug design efforts. Potential strategies
      in the detection of reactive intermediates in biochemical systems are also
      discussed. The intention of this review is not to "black list" functional groups
      or to immediately discard compounds based on their potential to form reactive
      metabolites, but rather to serve as a resource describing the structural
      diversity of these functionalities as well as experimental approaches that could
      be taken to evaluate whether a "structural alert" in a new drug candidate
      undergoes bioactivation to reactive metabolites.

PMID- 15975041
TI  - Trimethylamine: metabolic, pharmacokinetic and safety aspects.
AB  - Trimethylamine (TMA) is a volatile tertiary aliphatic amine that is derived from
      the diet either directly from the consumption of foods containing TMA, or by the
      intake of food containing precursors to TMA such as trimethylamine-N-oxide
      (TMNO), choline and L-carnitine. Following oral absorption in humans, TMA
      undergoes efficient N-oxidation to TMNO, a reaction catalyzed by the flavin
      containing monooxygenase (FMO) isoform 3 enzyme. TMNO subsequently undergoes
      excretion in the urine, although, evidence also suggests that metabolic retro
      reduction of TMNO can occur. Whilst the pharmacokinetics of TMA and TMNO has not
      been fully elucidated in humans, a number of studies provide information on the
      likely fate of dietary derived TMA. Trimethylaminuria is a condition that is
      characterized by a deficiency in FMO3 enzyme activity, resulting in the excretion
      of increased amounts of TMA in bodily fluids such as urine and sweat, and breath.
      A human FMO3 database has been established and currently twenty-eight variants of
      the FMO3 gene have been reported including twenty-four missense, three nonsense,
      and one gross deletion mutation. Whilst TMA and TMNO are generally regarded as
      non-toxic substances, they are of clinical interest because of their potential to
      form the carcinogen N-nitrosodimethylamine.

PMID- 15975042
TI  - Enzyme kinetics for clinically relevant CYP inhibition.
AB  - In vitro cytochrome P450 (CYP)-associated metabolic studies have been considered
      cost-effective for predicting the potential clinical drug-drug interactions
      (DDIs), one of the major attritions in drug development. The breakthroughs during
      the past decade in understanding the biochemistry of CYP-mediated
      biotransformation and molecular biology of CYP gene regulation in humans have
      provided the scientific bases for such endeavors in early drug development. In
      this review, the enzyme kinetics of CYP inhibitions is described, with the
      primary focus on the ones proven with clinical relevance, namely the competitive
      inhibition and mechanism-based inactivation (MBI). Competitive CYP inhibition,
      the most often detected reversible inhibition, is well understood and has been
      studied extensively both in vitro and in clinical setting. Recently, MBI has
      received increasing attention. It has been recognized that MBI could occur more
      often than anticipated, due in part to the redox cycling-allied enzymatic action
      of CYPs. As commonly as an irreversible inhibition, MBI would inactivate the
      target proteins, and thus would be generally considered of high potential for
      causing clinical DDI. Moreover, the reversible inhibitions other than the
      competitive, namely noncompetitive, uncompetitive and mixed, were also documented
      for the important drug-metabolizing CYP members, particularly CYP1A2 and CYP2C9.
      Finally, the unusual kinetic interactions, which did not follow the Michaelis
      Menten (M-M) kinetics, were detected in vitro for the majority of drug
      metabolizing CYP members, and manifested for CYP3A4. However, the clinical
      relevance of the interactions involving the unusual CYP kinetics has not yet been
      fully understood. Nonetheless, the reversibility and inhibitory potency should be
      considered as the major determinants of the clinical relevance, particularly in
      combination with the therapeutic exposure levels. With rapid expansion of
      knowledge and technology, the evaluation of the clinically relevant CYP
      associated DDIs in vitro is not only desirable but also achievable.

PMID- 15975043
TI  - Metabolism of designer drugs of abuse.
AB  - Abuse of designer drugs is widespread among young people, especially in the so
      called "dance club scene" or "rave scene", worldwide. Severe and even fatal
      poisonings have been attributed to the consumption of such drugs of abuse.
      However, in contrast to new medicaments, which are extensively studied in
      controlled clinical studies concerning metabolism, including cytochrome P450
      isoenzyme differentiation, and further pharmacokinetics, designer drugs are
      consumed without any safety testing. This paper reviews the metabolism of new
      designer drugs of abuse that have emerged on the black market during the last
      years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4
      methylthioamphetamine (4-MTA), were taken into consideration as new "classical"
      amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3,
      4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine
      (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine
      (MeOPP) were taken into consideration as derivatives of the class of piperazine
      derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'
      methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha
      pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone
      (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the
      class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing
      identification of in vivo or in vitro human or animal metabolites and cytochrome
      P450 isoenzyme dependent metabolism have been considered and summarized.

PMID- 15975044
TI  - Sulfation in dog.
AB  - Sulfation has been thoroughly studied in several species including e.g. man and
      rat. However, one important species often used for pharmacological drug studies
      is the dog. Here we describe recent advances as well as older data in the field
      of dog sulfation. Species differences in sulfation have been reported.
      Stereoselectivity, inhibition by pentachlorophenol, bioactivation of DNA binding
      species, and gender differences have also been observed for canine
      sulfotransferases (SULTs). Several drugs are being sulfated in vivo in dog, e.g.
      xamoterol, 4'-hydroxypropanolol, paracetamol and salicylamide. However, studies
      have shown that also e.g. canine hepatocytes and liverslices will sulfate
      substrates e.g. paracetamol and 7-hydroxycoumarin in in vitro experiments.
      Recently, three different enzymes have been cloned and characterized from canine
      liver, cSULT1A1, cSULT1B1 and cSULT1D1. cSULT1A1 being very similar to the human
      ortholog in terms of substrate specificity and is also ubiquitously expressed in
      canine tissues. The cSULT1B1 enzyme is also very similar in both distribution
      pattern as well as substrate preference compared to the human ortholog. The third
      enzyme, cSULT1D1, sulfates dopamine with high efficiency and it has no
      counterpart in man since it is found as a pseudogene. The importance of amino
      acid residue 247 in cSULT1D1 will be discussed since it can alter the ratio of
      sulfation of dopamine versus para-nitrophenol. In addition, the phenomenon of the
      high expression of the canine enzymes in colon is discussed.

PMID- 15975045
TI  - Antiangiogenic therapy in acute myelogenous leukemia: targeting of vascular
      endothelial growth factor and interleukin 8 as possible antileukemic strategies.
AB  - Acute myelogenous leukemia (AML) is an aggressive disorder with an overall
      disease-free survival of 40-50% even for the younger patients under 60 years of
      age who can receive the most intensive treatment. The median age at the time of
      diagnosis is 60-65 years, and the large majority of elderly patients usually
      receive less intensive chemotherapy or only supportive therapy due to the high
      treatment-related mortality when using intensive therapy for elderly individuals.
      Thus, there is a need for new therapeutic approaches to improve the treatment in
      younger patients and to make AML-directed therapy with acceptable toxicity
      possible in elderly individuals. Angiogenesis seems to be important both for
      leukemogenesis and susceptibility to intensive chemotherapy, and antiangiogenic
      strategies are therefore considered for the treatment of AML. The two
      proangiogenic mediators vascular endothelial growth factor (VEGF) and interleukin
      8, (IL-8, also referred to as CXCL8) seem to be important in human AML: VEGF is
      released at increased levels due to interactions between AML cells and
      neighboring nonleukemic cells, whereas IL-8 is released at high levels by native
      human AML cells. Thus, VEGF as a therapeutic target in AML is suggested both by
      experimental and clinical observations, whereas IL-8 as a target is mainly
      suggested by experimental evidence. In the present review we describe and discuss
      (i) the angioregulatory network of soluble mediators in AML, including both the
      systemic levels and local release by native human AML cells; and (ii) various
      therapeutic approaches to target VEGF and IL-8. Although single angioregulatory
      mediators can be targeted, it should be emphasized that the final effect of
      soluble mediators on angioregulation is determined by a complex angioregulatory
      network that varies between AML patients, and the final effect of targeting
      single mediators may therefore differ between patient subsets.

PMID- 15975046
TI  - The chick embryo chorioallantoic membrane as a model system for the study of
      tumor angiogenesis, invasion and development of anti-angiogenic agents.
AB  - Angiogenesis, the formation of new blood vessels, is essential for tumor growth,
      progression and metastasis. The development of agents that target tumor
      vasculature is ultimately dependent on the availability of appropriate
      preclinical screening assays. The chorioallantoic membrane (CAM) assay is well
      established and widely used as a model to examine angiogenesis, and anti
      angiogenesis. This review 1) summarizes the currently used angiogenesis assays
      and the importance of CAM model among them; 2) summarizes the current knowledge
      about the development and structure of the CAM's capillary bed; 3) reports
      findings regarding the role played by molecular signaling pathways in
      angiogenesis process; 4) discusses the use, advantages and limitations of the CAM
      as a model for studying tumor angiogenesis and invasiveness, as well as
      development of angiogenic and/or anti-angiogenic agents; 5) discusses the
      importance of standardization of the major methodologies for all aspects of the
      use of the CAM in angiogenesis-related studies; 6) and finally, summarizes major
      findings regarding the agents developed by the use of CAM model in the study of
      tumor angiogenesis, invasion and development of anti-angiogenic agents.

PMID- 15975048
TI  - The MYCN oncogene as a specific and selective drug target for peripheral and
      central nervous system tumors.
AB  - MYCN belongs to the MYC family of proto-oncogenes, which encode for transcription
      factors of the basic-helix-loop-helix-zipper (bHLHZ) class and is fundamental in
      the development of the peripheral and central nervous systems (PNS and CNS).
      While Myc is ubiquitous, MYCN has a very restricted expression pattern: it is
      mainly expressed during embryonic development, but then becomes downregulated,
      while in adults it is usually detected in B-cell development. Identification of
      selective inhibitors of MYCN and its mRNA and protein could be important for the
      development of more specific, effective and less toxic therapeutic agents for
      tumors of the PNS and CNS. In children, the most common tumors of the PNS and CNS
      are neuroblastomas and medulloblastomas, respectively. About 30% of neuroblastoma
      (NB) tumors present MYCN amplification/over-expression, which is associated with
      rapid progression and poor prognosis. N-Myc is essential during neurogenesis for
      the rapid expansion of progenitor cells in the brain. MYCN amplification and over
      expression has been reported in medulloblastoma, and especially in the
      desmoplastic type. Other tumors associated with MYCN overexpression include
      retinoblastoma, small cell lung carcinoma, glioblastoma and certain embryonal
      tumors. A cell-based, N-Myc-dependent luciferase reporter gene assay to identify
      specific N-Myc small-molecule inhibitors has allowed identification of five
      compounds showing significant activity. Antisense oligodeoxynucleotides have been
      shown to inhibit N-Myc production and anti-tumoral activity in vitro and in vivo
      for NB. Peptide nucleic acids (PNA), which belong to the most recent (third)
      generation of nucleic acid therapeutics, form highly stable duplexes with DNA and
      RNA, and are resistant to degradation by nucleases and proteases. Encouraging
      results have been reported utilizing a PNA-based antisense strategy for
      inhibition of N-Myc expression in neuroblastoma.

PMID- 15975047
TI  - Squalamine: a polyvalent drug of the future?
AB  - The purpose of this mini-review is to summarize and highlight the different
      advances in our understanding of the antimicrobial and antiangiogenic activity of
      squalamine, a cationic steroid isolated in 1993 from the dogfish shark Squalus
      Acanthias. Indeed, squalamine has shown to be useful for the treatment of
      important diseases such as cancers (lung, ovarian, brain and others), age-related
      macular degeneration (AMD) and the control of body weight in man. All these
      results led to a question: could we consider squalamine as a polyvalent drug of
      the future?

PMID- 15975049
TI  - Matrix metalloproteinase inhibitors as anticancer therapeutics.
AB  - Matrix metalloproteinases (MMPs), also designated as matrixins, play a central
      role in many biological processes and are involved both in physiologic cellular
      processes and in pathologic situations such as tumor growth, invasion and
      metastasis. For more than 30 years MMPs have been considered as promising targets
      for cancer therapy and a number of different synthetic and natural MMP inhibitors
      have been identified as cytostatic and anti-angiogenic agents and have begun
      clinical testing in view of their specific implication in malignant tissues.
      Although preclinical studies were so compelling to encourage several clinical
      trials, the past years have seen a consistent number of disappointments and
      limited success. The critical examination of previous studies shed light on new
      information about the cellular source, substrates and mode of action of MMPs,
      focusing the attention of future research on the identification of specific MMP
      targets in tumors at different stage of tumor progression, both in order to
      improve efficacy and to reduce the side effect profile. In this review we discuss
      the current view on the feasibility of MMPs as target for therapeutic
      intervention in cancer, taking into account that the perspective may be of great
      value for molecular medicine for the twenty-first century, providing intriguing
      information about the MMPs as mediators in biology and pathology, and as targets
      for disease therapies.

PMID- 15975050
TI  - The anti-tumor effect and mechanisms of action of penta-acetyl geniposide.
AB  - Gardenia, the fruit of Gardenia jasminoides Ellis, has been widely used to treat
      liver and gall bladder disorders in Chinese medicine. It has been shown recently
      that geniposide, the main ingredient of Gardenia Fructus, exhibits the anti-tumor
      effect. In this review, we discuss the anti-tumor effect and possible mechanisms
      of a derivative from Gardenia Fructus, penta-acetyl geniposide ((Ac)5GP). It has
      been demonstrated that (Ac)5GP plays more potent roles than geniposide in
      chemoprevention. (Ac)5GP decreased DNA damage and hepatocarcinogenesis induced by
      aflatoxin B1 (AFB1) by activating the phase II enzymes glutathione S-transferase
      (GST) and GSH peroxidase (GSH-Px). It reduced the growth and development of
      inoculated C6 glioma cells especially in pre-treated rats. In addition to the
      preventive effect, (Ac)5GP exerts its actions on apoptosis and growth arrest.
      Treatment of (Ac)5GP caused DNA fragmentation of glioma cells. (Ac)5GP induced
      sub- G1 peak through the activation of apoptotic cascades
      PKCdelta/JNK/Fas/caspase8 and caspase 3. Besides, p53/Bax signaling was suggested
      to be involved in (Ac)5GP-induced apoptosis, though its downstream cascades needs
      further clarified. (Ac)5GP has also been shown to inhibit DNA synthesis of tumor
      cells. It arrested cell cycle at G0/ G1 by inducing the expression of p21, thus
      suppressing the cyclin D1/cdk4 complex formation and the phosphorylation of E2F.
      The phosphorylation status of p53 on serine 392 correlated with the process of
      growth arrest. Evidences from the in vivo experiments showed that (Ac)5GP is not
      harmful to liver, heart and kidney. In conclusion, (Ac)5GP is highly suggested to
      be an anti-tumor agent for development in the future.

PMID- 15975052
TI  - Amyloid beta-peptide: the inside story.
AB  - The amyloid beta-peptide (Abeta) plays an early and critical role in the
      pathogenic cascade leading to Alzheimer's disease (AD). Abeta is typically found
      in extracellular amyloid plaques that occur in specific brain regions in the AD
      and Down syndrome brain. Mounting evidence, however, indicates that intraneuronal
      accumulation of this peptide may also contribute to the cascade of
      neurodegenerative events that occur in AD and Down syndrome. A pathogenic role
      for intracellular Abeta is not without precedent, as it is known to be an early
      and integral component of the human muscle disorder inclusion body myositis
      (IBM). Therefore, it is plausible that intracellular Abeta may likewise induce
      cytopathic effects in the CNS, causing neuronal and synaptic dysfunction and
      perhaps even neuronal loss. Here we review recent evidence supporting a
      pathogenic role for intracellular Abeta in AD, Down syndrome, and IBM.

PMID- 15975053
TI  - Alzheimer's disease: interactions between cholinergic functions and beta-amyloid.
AB  - Alzheimer's disease (AD) is characterized by two major features: (1) degeneration
      of basal forebrain cholinergic neurons and ensuing deficient cholinergic
      functions in cortex and hippocampus; (2) extracellular protein aggregates
      containing beta-amyloid peptides (Abeta) in these cholinergic target areas. So
      far, the most effective therapy for AD is to enhance cholinergic transmission.
      Neuromodulatory functions of the cholinergic system are mainly mediated by
      muscarinic receptors (mAChRs). It has long been recognized that mAChRs are
      crucial for the control of high-level cognitive processes. Drugs that activate
      mAChRs are helpful in ameliorating cognitive deficits of AD. On the other hand,
      mounting evidence have established detrimental effects of Abeta to cognitive
      functions. Despite intensive research on AD, it remains unclear how these two
      prominent features of the disease may be linked to cause cognitive impairments.
      In this review, we will summarize a series of recent findings on the interactions
      between cholinergic functions and beta-amyloid in normal animals and AD models,
      and discuss their potential implications in the pathophysiology and treatment of
      Alzheimer's disease.

PMID- 15975054
TI  - Acetylcholinesterase (AChE)--amyloid-beta-peptide complexes in Alzheimer's
      disease. the Wnt signaling pathway.
AB  - Alzheimer's disease (AD) is characterized by selective neuronal cell death, which
      is probably caused by amyloid beta-peptide (Abeta) oligomers and fibrils. We have
      found that acetylcholinesterase (AChE), a senile plaque component, increases
      amyloid fibril assembly with the formation of highly toxic complexes (Abeta
      AChE). The neurotoxic effect induced by Abeta-AChE complexes was higher than that
      induced by the Abeta peptide alone as shown both in vitro (hippocampal neurons)
      and in vivo (rats injected with Abeta peptide in the dorsal hippocampus).
      Interestingly, treatment with Abeta-AChE complexes decreases the cytoplasmic beta
      catenin level, a key component of Wnt signaling. Conversely, the activation of
      this signaling pathway by Wnt-3a promotes neuronal survival and rescues changes
      in Wnt components (activation or subcellular localization). Moreover Frzb-1, a
      Wnt antagonist reverses the Wnt-3a neuroprotection effect against Abeta
      neurotoxicity. Compounds that mimic the Wnt signaling or modulate the cross
      talking with this pathway could be used as neuroprotective agents for therapeutic
      strategies in AD patients.

PMID- 15975055
TI  - Functional interactions of tau and their relevance for Alzheimer's disease.
AB  - Abnormalities in tau modification and tau aggregation are a characteristic
      histopathological hallmark of Alzheimer's disease (AD). However it is less clear,
      how tau pathology is linked to other factors, e.g. the formation of amyloid
      plaques, mutations in the presenilin gene, or the ApoE genotype that all have
      been shown to contribute to the disease. In this article, data reporting tau's
      interactions with other factors that may be relevant for AD and that have been
      obtained from various types of in vitro experiments, cell culture experiments and
      animal models are summarized and brought into a mechanistic framework. Evidences
      for functional links of these interactions to neurodegenerative events
      characteristic for AD are discussed and weighed.

PMID- 15975056
TI  - Neurodegenerative disorders and cholesterol.
AB  - It has been suggested that a high serum cholesterol level is a risk factor for
      Alzheimer's disease (AD), that treatment with cholesterol-lowering drugs
      (statins) reduces the frequency of AD development, and that the polymorpholism of
      genes encoding proteins regulating cholesterol metabolism is associated with the
      frequency of AD development. However, the mechanism by which high serum
      cholesterol level leads to AD, still remains unclarified. Several recent studies
      have shown the results challenging the above notions. Here another notion is
      proposed, that is, a low high-density lipoprotein (HDL) level in serum and
      cerebro-spinal fluid (CSF) is a risk factor for the development of AD; moreover,
      the possibility that AD and Niemann-Pick type C disease share a common cascade,
      by which altered cholesterol metabolism leads to neurodegeneration (tauopathy) is
      discussed. In this review, the association between cholesterol and AD
      pathogenesis is discussed from different viewpoints and several basic issues are
      delineated and addressed to fully understand the mechanisms underlying this
      relationship.

PMID- 15975057
TI  - ROS effects on neurodegeneration in Alzheimer's disease and related disorders: on
      environmental stresses of ionizing radiation.
AB  - Neurodegenerative processes associated with Alzheimer's disease are complex and
      involve many CNS tissue types, structures and biochemical processes. Factors
      believed involved in these processes are generation of Reactive Oxygen Species
      (ROS), associated inflammatory responses, and the bio-molecular and genetic
      damage they produce. Since oxidative processes are essential to energy
      production, and to other biological functions, such as cell signaling, the
      process is not one of risk exposure, as for cigarettes and cancer, but one where
      normal physiological processes operate out of normal ranges and without adequate
      control. Thus, it is necessary to study the ambiphilicity that allows the same
      molecule (e.g., beta amyloid) to behave in contradictory ways depending upon the
      physiological microenvironment. To determine ways to study this in human
      populations we review evidence on the effects of an exogenous generator of ROS,
      ionizing radiation, in major population events with radionuclides (e.g.,
      Hiroshima and Nagasaki; Chernobyl Reactor accident; environmental contamination
      in Chelyabinsk (South Urals) where plutonium was produced, and in the nuclear
      weapons test area in Semipalatinsk, Kazakhstan). The age evolution, and traits,
      of neurodegenerative processes in human populations in these areas, may help us
      understand how IR affects the CNS. After reviewing human population evidence, we
      propose a model of neurodegeneration based upon the complexity of CNS functions.

PMID- 15975058
TI  - Molecular mechanisms, emerging etiological insights and models to test potential
      therapeutic interventions in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common cause of dementia, resulting from
      accumulated beta-amyloid protein deposits in the brain. As the population ages
      the incidence of AD is also on the rise. The incidence is very high in the
      developed countries where life expectancy is high, but it is also rising rapidly
      in the developing countries. Caring for patients suffering from AD is a major
      economic burden. The mechanisms underlying the neuropathology of AD are slowly
      being unravelled. Here we explore the many models and theories, which have been
      proposed over the years. We then discuss a potential therapeutic agent, vaccinia
      virus complement control protein (VCP), involved in modulating the complement
      system in AD. VCP has been shown in in vitro studies to block the complement
      activation caused by the beta peptide. Traumatic injuries to the brain are well
      known risk factors associated with the development of AD. VCP can also enhance
      functional recovery resulting from traumatic brain injury and may be able to slow
      the progression of traumatic brain injury to AD. Here we describe strategies for
      testing this hypothesis and evaluating other agents such as VCP.

PMID- 15975059
TI  - Biological markers of Alzheimer's disease and mild cognitive impairment.
AB  - The diagnosis of Alzheimer's disease (AD) is mainly performed by excluding other
      disorders with similar clinical features. In addition, an analysis of symptoms
      and signs, blood studies and brain imaging are major ingredients of the clinical
      diagnostic work-up. However, the diagnosis based on these instruments is
      unsatisfactory, indicating the need of a highly sensitive and reliable
      approaches, selective for AD and based on biological markers. Ideally, such
      markers should reflect the pathophysiological mechanisms of AD, which according
      to the current hypotheses, derive from the actions of two major protein
      aggregates, the extracellular beta-amyloid (Abeta) plaques and the
      neurofibrillary tangles. Since AD is a multifactorial disease, other factors that
      cause neuronal insult and that contribute to neuronal degeneration in AD include
      free radical and oxidative stress promoting molecules, proinflammatory cytokines
      and neurotoxic agents. In this context, the search for anomalous levels or
      changes in the molecular patterns of Abeta(1-42) or Abeta(1-40),
      hyperphosphorylated tau isoforms, oxidation products in the cell or cytokines
      such as interleukin-1 or 6 facilitates the selection of biomarkers in AD. There
      is clear evidence that the cerebrospinal fluid (CSF) levels of beta(1-42) are
      significantly reduced in AD patients as compared with senile controls, while
      increased levels of tau have been revealed. The CSF levels of these proteins
      reflect their metabolism in the central nervous system. Approaches using ELISA
      and immunochemical methods for the quantification of these markers in CSF have
      been preferentially used. Diagnosis criteria and number of patients exhibits
      variations in the different reports, while clinico-pathological studies are
      scarce. An increasing number of studies suggest that supplementary use of these
      CSF markers preferably in combination, adds to the accuracy of an AD diagnosis.

PMID- 15975060
TI  - Cardiac effect of cholinesterase inhibitors used in Alzheimer's disease--from
      basic research to bedside.
AB  - In this review, the basic mechanism of the parasympathetic nervous effect on the
      heart is discussed. This is expanded to clinical situations to clarify what can
      happen to patients after cholinesterase (ChE) inhibitor is administered and to
      avoid unnecessary adverse effects. The parasympathetic nervous system can affect
      heart as well as brain function, and its effect on the heart is more complicated
      than is generally thought. The best-known effect is the cardioinhibitory effect,
      i.e. slowing of the heart rate. Its effect is also very sensitive to the time at
      which the stimulus falls within the cardiac cycle (phase-dependent effect). On
      some occasions, a cardiostimulatory effect can be observed. The parasympathetic
      nervous system also interacts with the sympathetic nervous system (sympathetic
      parasympathetic interaction). ChE inhibitors or acetylcholinesterase inhibitors
      are often being administered to improve cognitive function of patients with
      Alzheimer's disease. The heart is naturally rich with ChE, and its inhibition may
      affect cardiac function, especially in elderly patients, many of whom have
      concomitant cardiovascular disease. Inhibition of ChE retards ACh degradation and
      potentiates the cardioinhibitory effect. However, the effect of ChE inhibitor is
      only slight in patients that receive a typical dose. After administration of ChE
      inhibitor in humans, the phase-dependent effect is reduced because the
      parasympathetic nervous effect is potentiated and saturated (saturation
      mechanism). Beat-by-beat fluctuation is reduced. ChE inhibitor increases arterial
      blood pressure through central M1 and M2 subtypes of muscarinic receptors (Br J
      Pharmacol 127:1657-1665, 1999). However, diastolic blood pressure increases
      slightly.

PMID- 15975062
TI  - Advances in the four major pillars of Alzheimer's disease research: pathobiology,
      genetics, diagnosis, and treatment.

PMID- 15975061
TI  - Regression to the mean: implications for clinical trials of psychotropic agents
      in dementia.
AB  - Effective drug development depends on understanding and optimizing results from
      controlled clinical trials. A recent double-blind, randomized, controlled trial
      of the treatment of agitation in patients with Alzheimer's disease (AD) found no
      difference among the four arms of the study: haloperidol, trazodone, behavioral
      therapy, placebo. The current analysis was undertaken to further investigate the
      issues bearing on this outcome and to identify better means of detecting
      psychotropic effects in trials involving patients with AD. This was post hoc
      analysis of a clinical trial data set. Patients in the placebo group were divided
      into responders (25% reduction in symptoms), worseners (25% worsening in baseline
      agitation scores), and those without a change in symptoms. Analysis of the trial
      outcomes demonstrated that the reduction observed in the placebo group was of the
      same magnitude as predicted by regression to the mean. Patients exhibiting
      greater improvement had more severe baseline behavioral disturbances. The
      relatively modest severity of agitation and the low medication doses achieved in
      the study may have further contributed to the failure to distinguish among
      treatment groups. Research design adjustments such as collection of both
      screening and baseline measures to determine eligibility may limit the effects of
      regression to the mean on trial outcomes and reduce this challenge to clinical
      trials.

PMID- 15975063
TI  - Alzheimer's disease and immunotherapy.
AB  - Site-directed antibodies which modulate conformation of beta-amyloid peptide
      became the theoretical basis of the immunological approach for treatment of
      Alzheimer's disease (AD). Indeed, antibodies towards the EFRH sequence, located
      between amino acids 3-6 of the N-terminal region of Alzheimer's AbetaP, found to
      be a key position in protein conformation modulation, suppress formation of beta
      amyloid and dissolve already formed fibrillar amyloid. The performance of anti
      beta-amyloid antibodies in transgenic mice models of AD showed they are delivered
      to the central nervous system (CNS), preventing and dissolving beta-amyloid
      plaques. Moreover, these antibodies protected the mice from learning and age
      related memory deficits. Naturally occurring anti-AbetaP antibodies have been
      found in human CSF and in the plasma of healthy individuals, but were
      significantly lower in AD patients, suggesting that AD may be an immunodeficient
      disorder. Active and/or passive immunization against beta-amyloid peptide has
      been proposed as a method for preventing and/or treating Alzheimer's disease.
      Experimental active immunization with Abeta 1-42 in humans was stopped in phase
      II clinical trials due to unexpected neuroinflammatory manifestations. Antibodies
      generated with this first-generation vaccine might not have the desired
      therapeutic properties to target the "correct" mechanism, however, new clinical
      approaches are now under consideration. Immunotherapy represents fascinating ways
      to test the amyloid hypothesis and offers genuine opportunities for AD treatment,
      but requires careful antigen and antibody selection to maximize efficacy and
      minimize adverse events.

PMID- 15975064
TI  - ADAM proteases: protective role in Alzheimer's and prion diseases?
AB  - Alzheimer's disease, as well as most of other neurodegenerative disorders, is
      characterized by the deposition of insoluble proteinaceous aggregates. Hence, any
      intervention aimed at reducing this process could be envisioned as a therapeutic
      way to slow down the disease. In the case of Alzheimer's disease, the culprit
      protein is the 40-43 amino acid-long amyloid beta peptide (Abeta). This fragment
      is generated from the beta-amyloid precursor protein (betaAPP) by two distinct
      enzymes, namely the beta- and the gamma-secretases. In the past years, a
      tremendous effort has been made to develop potent and specific inhibitors of
      these proteolytic activities. Beside these Abeta-forming proteases, a third
      cleavage performed by the so-called alpha-secretase takes place in the middle of
      the Abeta sequence and not only precludes its formation but also generates the
      secreted product sAPPalpha that possesses neurotrophic and neuroprotective
      properties. This beneficial cleavage has been shown to be strongly upregulated by
      protein kinase C (PKC) agonists and to be, at least partially, triggered by ADAM
      proteases (A Disintegrin And Metalloprotease). Recently, a proteolytic attack
      with similar characteristics has been shown to occur in the middle of the "toxic"
      106-126 domain of the prion protein (PrPc), which PrPsc isoform is the causative
      agent of transmissible spongiform encephalopathies. As both Abeta and PrP(106
      126) trigger neurotoxicity and cell death, this ADAM-dependent proteolytic attack
      could represent a valuable therapeutic target in order to deplete cells from
      these endogenous "toxins"and prevent the associated aggregates usually detected
      in affected brains.

PMID- 15975065
TI  - Uncovering gamma-secretase.
AB  - Accumulation of the amyloid beta-peptide (Abeta) in the brain is believed to
      initiate a series of neurotoxic events that causes neurodegeneration in
      Alzheimer's disease (AD). Abeta is generated by processing of the beta-amyloid
      precursor protein (APP) through the successive action of two proteolytic enzymes,
      beta-secretase and gamma-secretase. While beta-secretase has been identified as
      the membrane-bound aspartyl protease BACE, the identity of gamma-secretase, which
      catalyzes the final, intramembrane cleavage of APP as well as of several other
      type I transmembrane proteins, has been enigmatic for a long time. Exciting
      progress has been made in the past year towards its uncovering. Genetics paved
      the way for subsequent biochemical reconstitution studies that demonstrated that
      gamma-secretase is a protein complex composed of presenilin (PS), nicastrin
      (NCT), APH-1 and PEN-2. Thus, the complete set of genes that is required to
      generate Abeta from its precursor has now ultimately been identified. PS carries
      the active site of gamma-secretase and is a founding member of a novel class of
      polytopic aspartyl proteases that utilize a non-classical active site to cleave
      their membrane-tethered substrates. The other components are required for
      assembly, stabilization and maturation of the complex and NCT may be involved in
      the recognition of gamma-secretase substrates.

PMID- 15975066
TI  - Walnut extract inhibits the fibrillization of amyloid beta-protein, and also
      defibrillizes its preformed fibrils.
AB  - Fibrillar amyloid beta-protein (Abeta) is the principal component of amyloid
      plaques in the brains of patients with Alzheimer's disease. We have studied the
      effect of walnut extract on Abeta fibrillization by Thioflavin T fluorescence
      spectroscopy and electron microscopy. The walnut extract not only inhibited Abeta
      fibril formation in a concentration and time- dependent manner but it was also
      able to defibrillize Abeta preformed fibrils. Over 90% inhibition of Abeta
      fibrillization was observed with 5 microl of methanolic extract of walnut (MEOW)
      both after 2 and 3 days of incubation. The maximum defibrillization (91.6%) was
      observed when preformed Abeta fibrils were incubated with 10 microl of MEOW for 2
      days. These results suggest that walnuts may reduce the risk or delay the onset
      of Alzheimer's disease by maintaining Abeta in the soluble form. Further studies
      showed that anti-amyloidogenic compound in walnut is an organic compound of
      molecular weight less than 10 kDa, which is neither a lipid nor a protein.
      Chloroform extract of walnut had no effect on Abeta fibrillization while MEOW and
      its 10 kDa filtrate inhibited Abeta fibrillization equally. It is proposed that
      polyphenolic compounds (such as flavonoids) present in walnuts may be responsible
      for its anti-amyloidogenic activity.

PMID- 15975067
TI  - Lesions and dysfunctions of the nucleus basalis as Alzheimer's disease models:
      general and critical overview and analysis of the long-term changes in several
      excitotoxic models.
AB  - The cholinergic hypothesis of Alzheimer's Disease (AD) has led to a number of
      animal models to study in vivo the pathogeny of cortical cholinergic involution.
      The lesion of the cholinergic neurons of the basal forebrain, especially of the
      nucleus basalis magnocellularis (nbm) of rodents, has been the most utilized
      method for obtaining these models. Toxic substances such as quinolic, kainic,
      NMDA, ibotenic and quisqualic acids, the specific cholinergic toxin AF64,
      amyloid, and antibodies to neurotrophic factors; etc, have been used to produce
      such lesions. These investigations have helped our understanding of the role of
      cerebral cholinergic innervation in cognitive disorders and their treatments.
      However, this research has provided conflicting results, and much controversy has
      developed surrounding the role of the cholinergic systems and the suitability of
      these models. It is very important to take into account the exact type of
      nbm/cortical lesion produced, and its evolution, if meaningful results are to be
      obtained. This review covers the theoretical and practical use of nbm lesion
      models, and examines the main positive and negative results obtained by different
      authors in the light of our own observations on the long-term (3 years)
      morphological and biochemical changes that occur in several kinds of nbm-lesion
      model rats. The changes seen were very different, but many of them were increased
      up to the end of life with no clear relationship with the development of the
      original lesion.

PMID- 15975068
TI  - Prevalence of pathogenic mutations in an Italian clinical series of patients with
      familial dementia.
AB  - Genetic factors are involved in the aetiology of dementias. Three genes have been
      identified which, when mutated, cause Familial Alzheimer disease (FAD): the
      presenilin-1 (PS1), the presenilin-2 (PS2) and the amyloid precursor protein
      (APP) genes. Together, these mutations are responsible for 30-50% of the cases
      with autosomal dominant Alzheimer disease (AD), and for about 5% of all AD cases.
      While over 130 mutations have been identified in PS1, mutations in PS2 and APP
      are rarer, since only 10 and 22 mutations, respectively, have been found in these
      FAD genes. Instead, mutations in the MAPT gene were associated with Familial
      Frontotemporal dementia (FFTD) linked to chromosome 17 (FTDP-17). Frontotemporal
      dementia (FTD) can occur in a sporadic form, but in 30-50% of cases there is a
      positive family history of dementia. In this study, we determined the spectrum of
      mutations and the relative contribution of the above mentioned four genes in our
      Italian clinical series of patients with a positive family history of dementia.

PMID- 15975069
TI  - New approaches in nuclear medicine for early diagnosis of Alzheimer's disease.
AB  - Dementia, Alzheimer's disease (AD) being the most common cause of it, is a major
      and growing medical and social problem, particularly in the advanced age, with
      the highest rate in the population over 75 y. Recent sophisticated therapeutic
      measures require more sensitive diagnostic tests to recognize early stages of the
      disease. In this paper, the current neuronuclear imaging literature is reviewed
      with regard to early and differential diagnosis of dementia. Functional imaging
      with single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) could provide the clinician with additional information
      complementary to morphological assessments, thus contributing to achieve a more
      adequate diagnosis, and also with information regarding prodromal stages of AD.

PMID- 15975071
TI  - New insights into serotonin 5-HT4 receptors : a novel therapeutic target for
      Alzheimer's disease?
AB  - The serotonin 5-HT4 receptor mediates many physiological effects in the central
      nervous system. The recent molecular identification of 5-HT4 receptors and the
      development of selective 5-HT4 receptor ligands have led to many important new
      insights into the signalling pathways and the physiological roles of these G
      protein-coupled-receptors in neurones. With respect to neurodegenerative
      disorders, it is suggested that 5-HT4 agonists may represent a new avenue for the
      treatment of Alzheimer's disease. This mini-review will focus on recent in vitro
      and in vivo pharmacological and biochemical studies showing the involvement of 5
      HT4 receptors in cognitive processes and the amyloid precursor protein
      processing. The potential use of 5-HT4 agonists for the treatment of AD will be
      discussed.

PMID- 15975072
TI  - Disruption of calcium homeostasis in the pathogenesis of Alzheimer's disease and
      other conformational diseases.
AB  - Conformational changes of Alzheimer's beta-amyloid protein (AbetaP) enhance its
      neurotoxicity and play important roles in the pathogenesis of Alzheimer's
      disease. Recent studies have suggested that a common mechanism is based on
      diverse "conformational diseases". They share similarity in their formation of
      beta-sheet containing amyloid fibrils by disease-related proteins and the
      introduction of apoptotic degeneration. Numerous studies, including our own, have
      revealed that AbetaP and several disease-related proteins are capable of directly
      incorporating into membranes, forming calcium-permeable ion channels, and causing
      abnormal elevation of intracellular calcium levels. This article reviews the
      current understanding of the pathology of conformational diseases based on the
      hypothesis that the disruption of calcium homeostasis through amyloid channels
      may form the molecular basis of neurotoxicity of AbetaP and other disease-related
      proteins. The roles of membrane lipids and potential development of preventive
      agents are also discussed.

PMID- 15975073
TI  - Assembly in vitro of tau protein and its implications in Alzheimer's disease.
AB  - Tau is a microtubule associated protein that is also the main component of the
      aberrant filaments that form aberrant structures like the neuropil threads or the
      neurofibrillary tangles, found in the brain of Alzheimer's disease patients. The
      assembly of tau aberrant filaments could be reproduced in vitro by using a high
      concentration of tau protein or, at lower protein concentrations, by adding some
      compounds like polyanions, fatty acids (and derivates), and others. In this mini
      review a descriptive analysis of the different conditions needed for in vitro tau
      polymerization are summarized.

PMID- 15975074
TI  - Increased susceptibility to plasma lipid peroxidation in Alzheimer disease
      patients.
AB  - Oxidative stress, linked to Abeta-lipid interactions, plays a pathogenetic role
      in Alzheimer's disease. We investigated modifications of lipid peroxidation
      products in plasma of 52 AD patients, 42 healthy controls and 16 patients with
      amyotrophic lateral sclerosis, a neurodegenerative disease where oxidative stress
      also plays a pathogenetic role. Final lipid peroxidation products were measured
      in plasma by thiobarbituric acid reactive substances (TBARS) assay before and
      after ex vivo oxidative stress catalysed by copper. There were no significant
      changes at basal conditions, but after copper-induced oxidation TBARS levels were
      higher in AD patients (19.0 microM +/- 2.2) versus both controls (5.2 microM +/-
      0.8, p<0.001) and ALS patients (7.6 microM +/- 2.1, p<0.01). Stimulated TBARS
      levels were significantly higher in mild and moderate AD (p<0.0001) with respect
      to controls, but not in severe AD patients, with a significant inverse
      correlation between disease severity and lipid peroxidation (p<0.005, r2=0.21).
      Treatment of a subgroup (13) of mild and moderate AD patients with vitamin C and
      E for three months decreased plasma lipoperoxidation susceptibility by 60%. Thus,
      oxidative stress, expressed as ex vivo susceptibility to lipid peroxidation,
      appears to be an early phenomenon, probably related to AD pathogenetic
      mechanisms.

PMID- 15975075
TI  - Reactive oxygen and nitrogen species in Alzheimer's disease.
AB  - Age- related neurodegenerative diseases, especially Alzheimer's disease (AD), are
      an important health problem globally. AD is clinically characterized by loss of
      memory, reasoning and speech. The frequency of the disease reaches to 20-40% in
      the population over the age of 85. Autopsy findings have indicated the presence
      of senile plaques and neurofibrillary tangles in the brains of patients with AD.
      These two lesions can be seen in small numbers during normal aging of the brain
      but occur in large amounts during AD. Although the initiating causes leading to
      AD are unknown, oxidative damage appears to play an important role in the slowly
      progressive neuronal death that is characteristic of AD. Indeed, in addition to
      the presence of senile plaques and neurofibrillary tangles, postmortem analysis
      of AD brain has also identified markers of oxidative stress including protein
      nitrotyrosine, carbonyls in proteins, lipid oxidation products and oxidized DNA
      bases. This review discusses the role of reactive oxygen and nitrogen species in
      the pathogenesis of AD and examines the relevance of antioxidant therapy in
      altering and/or inhibiting neurodegeneration associated with the disease.

PMID- 15975076
TI  - The role of P-glycoprotein in cerebral amyloid angiopathy; implications for the
      early pathogenesis of Alzheimer's disease.
AB  - It has been shown in vitro that beta-amyloid (Abeta) is transported by P
      glycoprotein (P-gp). Previously, we demonstrated that Abeta immunoreactivity is
      significantly elevated in brain tissue of individuals with low expression of P-gp
      in vascular endothelial cells. These findings led us to hypothesize that P-gp
      might be involved in the clearance of Abeta in normal aging and particularly in
      Alzheimer's disease (AD). As we were interested in the early pathogenesis of
      Abeta deposition, we studied the correlation between cerebral amyloid angiopathy
      (CAA) and P-gp expression in brain tissue samples from 243 non-demented elderly
      cases (aged 50 to 91 years). We found that endothelial P-gp and vascular Abeta
      were never colocalized, i.e., vessels with high P-gp expression showed no Abeta
      deposition in their walls, and vice versa. Abeta deposition occurred first in
      arterioles where P-gp expression was primarily low, and disappeared completely
      with the accumulation of Abeta. At this early stage, P-gp was upregulated in
      capillaries, suggesting a compensatory mechanism to increase Abeta clearance from
      the brain. Capillaries were usually affected only at later stages of CAA, at
      which point P-gp was lost even in these vessels. We hypothesize that Abeta
      clearance may be altered in individuals with diminished P-gp expression due,
      e.g., to genetic or environmental effects (such as drug administration). The
      impairment of Abeta clearance could lead to the accumulation and earlier
      deposition of Abeta, both in the walls of blood vessels and in the brain
      parenchyma, thus elevating the risk of CAA and AD.

PMID- 15975078
TI  - Neurobiology and genetics of behavioural syndromes of Alzheimer's disease.
AB  - The number of people with cognitive impairment is rising in parallel with
      changing demographics. As health care budgets are coming under increasing strain
      with regard to the provision of nursing care, there is a substantial need for
      effective therapies which encompass greater understanding of the components of
      dementia that finally necessitate admission to residential or nursing home care.
      Behavioural and psychological symptoms of dementia (BPSD) are major independent
      risk factors for admission to institutional care and research into the origin of
      BPSD is gathering pace. In this review, we evaluate the neurobiological and
      genetic changes described in individuals with BPSD in Alzheimer's disease.
      Particular emphasis is placed on genetic theories of causation, namely that BPSD
      results directly or indirectly from known genetic risk factors for AD, or
      distinct genetic risk factors for psychiatric illness assume clinical
      significance within the degenerated Alzheimer's brain.

PMID- 15975077
TI  - Cystathionine beta synthase as a risk factor for Alzheimer disease.
AB  - One of the known risk factors for developing Alzheimer disease (AD) is
      hyperhomocysteinemia. The latter may result from mutations of the genes coding
      for three key enzymes involved in homocysteine metabolism
      (methylenetetrahydrofolate reductase [MTHFR], methionine synthase [MS], and
      cystathionine beta-synthase [CBS]). Although MTHFR and MS polymorphisms have been
      shown to be positively associated with AD in some populations, the relationship
      of the CBS gene with AD remains undefined. In order to evaluate whether AD is
      associated with CBS gene changes leading to decreased CBS activity and
      homocysteine accumulation, we genotyped the CBS 844ins68 mutation and VNTR
      polymorphisms of the CBS gene in 206 AD patients and 186 age-matched controls. A
      slight increase in both 844ins68 mutation and VNTR allele 19 frequencies was
      detected in the whole AD patient group, compared with controls. The division of
      AD patients and controls into three age-at-onset/age dependent subgroups (<65
      years, 65-74 years, > 75 years) revealed that the 844ins68 mutation and VNTR
      allele 19 are independent risk factors for AD development in subjects aged 75
      years or more.

PMID- 15975079
TI  - Correlation of Alzheimer-like tau hyperphosphorylation and fMRI bold intensity.
AB  - To explore the correlation between cerebral functional alterations revealed by
      functional magnetic resonance imaging (fMRI) and Alzheimer disease- (AD)-like tau
      hyperphosphorylation, we injected bilaterally 2 microl each of 20 mM
      isoproterenol (IP), a PKA activator, or of saline as a vehicle control into the
      hippocampus of rats. FMRI was employed to measure the intensity of BOLD signal,
      one of the cerebral functional markers reflecting the changes of cerebral
      metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), in hippocampus
      and cortex 24 h after the operation. Immunohistochemical staining of hippocampus
      and cortex was carried out using phosphorylation-dependent tau antibodies. The
      results showed (1) that BOLD intensity in hippocampus and cortex of IP-injected
      rats was obviously lower than that of sham-operated group, indicating a decrease
      in CMRO2 and CBF of the particular brain regions in IP-treated rats; (2) that tau
      was hyperphosphorylated at Ser-262/Ser-356 (12e8), Ser-396/Ser-404 (PHF-1) sites
      in CA1 CA2 CA3 CA4 and dentate gyrus regions of hippocampal formation and cortex
      area in IP group, but not in sham rats; (3) that a negative correlation between
      tau hyperphosphorylation and BOLD intensity in hippocampus and cortex area of IP
      rats was observed. The data suggested that hippocampal and cortical tau
      hyperphosphorylation was intimately related to BOLD intensity of the same areas.
      To our knowledge, this is the first report exploring the relationship between
      fMRI BOLD signal and AD-like tau hyperphosphorylation.

PMID- 15975080
TI  - Protein trafficking and Alzheimer's disease.
AB  - Mutations in presenilin 1 (PS1) cause early-onset familial Alzheimer;s disease
      (FAD). Although FAD accounts for less than 5% of all cases of Alzheimer;s disease
      (AD), extensive analyses of PS1 function have elucidated an important neuronal
      mechanism underling AD pathogenesis. PS1 is considered to be an essential
      component of gamma-secretase, which cleaves amyloid precursor protein (APP) at
      the transmembrane region and releases amyloid beta (Abeta) peptide. In addition
      to this well-documented function, a growing amount of evidence suggests that PS1
      is involved in the intracellular trafficking of selected membrane proteins (i.e.
      APP, nicastrin, trkB, telencephalin). Recently, we have also shown that PS1 is
      involved in the trafficking of N-cadherin from the endoplasmic reticulum to the
      plasma membrane via the microtubule network. N-cadherin is localized at the
      synaptic junctional complex, providing an adhesive force across the synaptic
      cleft, and the its regulation is crucial for the neuron to exert its specific
      function, i.e. synaptic activity. In a mature neuron, polarized targeting of
      proteins from the cell body to the axonal and dendritic processes is essential
      for its proper function, especially, for the maintenance of synaptic function.
      Alterations in protein transport caused by a dysfunction in PS1 could lead to a
      disturbance in synaptic transmission and finally to neurodegeneration. This
      article will review the current knowledge of PS1 function in protein trafficking
      and discuss its potential role in AD pathogenesis.

PMID- 15975081
TI  - The identification and characterization of excitotoxic nerve-endings in Alzheimer
      disease.
AB  - Regionally specific neuronal loss is a distinguishing feature of Alzheimer
      disease (AD). Excitotoxicity is a mechanism commonly invoked to explain this. We
      review the accumulating evidence for such a hypothesis, particularly the altered
      expression and pharmacology of glutamate receptors and transporters in
      pathologically susceptible regions of the AD brain. Loss of neurons would be
      expected to lead to the retrograde degeneration of their afferents, which should
      be reflected in a loss of presynaptic markers such as synaptophysin. We discuss
      the possibility that neurons may be destroyed locally, but that glutamatergic
      presynaptic terminals may remain, or even re-proliferate. The reduced glutamate
      uptake site density in AD brain may signify a loss of the transporters on
      otherwise intact terminals, rather than the loss of glutamatergic afferents.
      Neuronal death may follow if cells are exposed to excessive amounts of glutamate;
      the loss of transporters from functioning, but defective, glutamate terminals
      would mean they could continue to release glutamate to exacerbate excitotoxicity.
      We discuss experimental methods to quantitate synapses, which are crucial for
      deciding between the various possibilities.

PMID- 15975082
TI  - Mechanisms of synaptic homeostasis in Alzheimer's disease.
AB  - Despite considerable progress in defining the role of the beta-amyloid protein
      (Abeta) in the pathogenesis of Alzheimer's disease (AD), the mechanism by which
      accumulation of Abeta causes dementia remains elusive. Memory loss is probably
      caused by an Abeta-induced change in synaptic plasticity. Computational
      neuroscience (neural network modelling) studies demonstrate that cell death (or
      synaptic loss as a consequence of cell death) per se cannot cause the specific
      pattern of gradual amnesia that occurs in AD. Amnesia typical of that seen in AD
      can only be produced when synaptic scaling occurs. Synaptic scaling is a
      compensatory homeostatic mechanism which maintains the excitatory response of
      individual neurons and prevents the catastrophic amnesia associated with synapse
      loss. In this review, several possible mechanisms of synaptic scaling are
      described.

PMID- 15975083
TI  - Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer's disease.
AB  - Based on a growing literature, cyclin-dependent kinase 5 (Cdk5) has been
      implicated in the pathological processes that contribute to neurodegeneration in
      Alzheimer's disease (AD). Cdk5 is ubiquitously expressed, but its activity is
      largely localized to post-mitotic neurons due to neuron-specific expression of
      its activators p35 and p39. Sufficient Cdk5 activity is critical to normal
      central nervous system development, as in its absence, neuronal migration and
      axonal path finding are deranged. Conversely, excessive and mislocalized Cdk5
      activity appears to be detrimental to neuronal function. In fact, the
      pathological hallmarks of AD, beta-amyloid aggregates and neurofibrillary
      tangles, have been linked to Cdk5-mediated neuronal death. In this model, beta
      amyloid is the toxic stimulus that disrupts intracellular calcium homeostasis,
      leading to activation of calpains, a family of calcium-dependent proteases.
      Calpain-mediated cleavage of p35, yields a truncated p25 fragment that possesses
      a longer half-life, lacks the necessary sequence targeting it to membranes, but
      retains the capacity to activate Cdk5. The resulting excessive and mislocalized
      Cdk5 activity targets tau as a substrate for hyperphosphorylation, which is a
      prerequisite of paired helical filament (PHF) formation. A number of recent
      reports, utilizing diverse methods, lend further support to this model of AD
      neurodegeneration, and several strategies for combating Cdk5 dysregulation have
      even been devised. However, the study of Cdk5 in AD is not without controversy,
      and questions remain regarding its role in the pathology. Herein, the most recent
      findings regarding this model are reviewed.

PMID- 15975084
TI  - Involvement of advanced glycation end-products (AGEs) in Alzheimer's disease.
AB  - The advanced stage of the glycation process (one of the post-translational
      modifications of proteins) leads to the formation of advanced glycation end
      products (AGEs) and plays an important role in the pathogenesis of angiopathy in
      diabetic patients. It has recently become clear that AGEs also influence
      physiological aging and neurodegenerative diseases such as Alzheimer's disease
      (AD) and amyotrophic lateral sclerosis (ALS). Recently we have provided direct
      immunochemical evidence for the existence of six distinct AGE structures within
      the AGE-modified proteins and peptides that circulate in the serum of diabetic
      patients on hemodialysis (DM-HD). We showed a direct toxic effect of the
      synthetic AGE-2 (glyceraldehyde-derived AGEs) on cortical neuronal cells and
      provided evidence for a toxic effect of AGE-2 present in DM-HD serum. These
      results indicate that of the various types of AGE structures that can form in
      vivo, the AGE-2 structure is likely to play an important role in the
      pathophysiological processes associated with AGE formation. In AD brains, AGE-2
      epitope was mainly present in the cytosol of neurons in the hippocampus and para
      hippocampal gyrus. Protein cross-linking by AGE structures results in the
      formation of protease-resistant aggregates. Such protein aggregates may interfere
      with both axonal transport and intracellular protein traffic in neuron. In this
      review, we provide an outline of AGEs formation in vivo and propose that the
      novel structural epitope AGE-2 is an important toxic moiety for neuronal cells in
      AD.

PMID- 15975085
TI  - The clinical and biological relationship between Type II diabetes mellitus and
      Alzheimer's disease.
AB  - The clinical relationship between Type II diabetes mellitus and Alzheimer's
      disease has been debated for over a decade. While several studies have not shown
      a clear clinical correlation, others have demonstrated that Type II diabetes is
      an independent risk factor for Alzheimer's disease. Why diabetes would increase
      the likelihood of Alzheimer's disease is not immediately clear, although recent
      studies have demonstrated an impact of insulin abnormalities, insulin resistance
      and advanced glycation end products on both the development of neural amyloid
      plaques and neurofibrillary tangles. Although endodermal in embryologic
      development, the pancreas is a highly innervated organ that shares a number of
      molecular similarities with brain at the level of the transcriptome and proteome.
      Type II diabetes and Alzheimer's disease are characterized by localized amyloid
      deposits that progress during the course of the disease. Comparing amyloid
      deposition in the brain and pancreas reveals some striking pathophysiologic
      similarities. Neurodegeneration in pancreatic islets, as manifested by
      neurofibrillary tangles, is less well studied than in Alzheimer's disease but may
      also occur. This review summarizes what is currently known about the clinical and
      biological relationships and similarities between Type II diabetes and
      Alzheimer's disease.

PMID- 15975086
TI  - Cross-cultural comparison of mild cognitive impairment between China and USA.
AB  - Individuals with mild cognitive impairment (MCI) are at increased risk for
      dementia of Alzheimer's type (DAT), vascular dementia (VaD), Lewy Body (LBD) and
      Fronto-temporal dementias (FTD). Risk factors and conversion rates of MCI to
      dementia have not been thoroughly investigated in developing countries. Chinese
      and English versions of Mini-Mental State Examination were administered serially
      among well-matched subjects from two clinics located in Xi'an, China and Houston,
      USA. Subtle cognitive impairments were weighed according to MCI criteria as
      defined previously. Subjects with MCI were followed for an additional 3 years
      after their identification. Diagnoses of VaD and DAT were made according to
      established criteria. During screening period, 73 American and 65 Chinese
      individuals were identified with MCI. After 3 years of MCI follow-up, of the 73
      American MCI subjects, 35 (47.9%) developed DAT and 15 (20.5%) developed VaD. Of
      the 65 Chinese MCI subjects, 12 (18.5%) developed DAT and 19 (29.2%) developed
      VaD. According to Kaplan-Meier analysis, Chinese MCI subjects, despite their
      lower educational level, are 1.7 times less likely to progress to DAT and 2.3
      times more likely to progress to VaD than American subjects within 3 years of MCI
      being identified (p<0.01). Data suggest that progression rates of MCI vary
      considerably among subjects from two countries. American MCI subjects are more
      prone to DAT, while Chinese subjects are more prone to VaD. Differences in
      genetic factors, cultures, educational levels, and preventive treatments of
      vascular risk factors are proposed as responsible for this uneven geographic
      distribution for different types of dementia.

PMID- 15975087
TI  - Cognitive event-related potentials: useful clinical information in Alzheimer's
      disease.
AB  - Cognitive event-related potentials (ERPs) have been used as a marker of cognitive
      function in patients with psychiatric and neurological disorders. In particular,
      the P300 potential has been widely utilized to study dementia and aging, because
      the P300 ERP component is easily observed and reflects attention and memory
      processing. However, the relationship between parameters of the P300 potential
      and the severity or type of cognitive impairment in patients with Alzheimer's
      disease (AD) remains controversial. Because specific and effective anti-dementia
      treatments have recently become available for AD, more useful information is
      needed about the clinical aspects of this disease, including methods of making an
      accurate and early diagnosis, differentiation from vascular dementia and other
      degenerative dementias, assessment of severity, assessment of disease
      progression, evaluation of the response to treatment, and prediction of the
      prognosis. This mini-review described new discoveries on recent clinical
      application of ERPs in AD with respect to the above-mentioned areas. Although the
      definition of normal ERP values and the most appropriate method of ERP recording
      in AD patients have not been well defined, recent findings suggest that ERP
      analysis may be a clinically useful, inexpensive, noninvasive, and reliable
      method of assessing AD.

PMID- 15975088
TI  - The effects of gender and CYP46 and apo E polymorphism on 24S-hydroxycholesterol
      levels in Alzheimer's patients treated with statins.
AB  - To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma
      levels of 24S-hydroxycholesterol in Alzheimer's disease (AD) patients and to
      determine whether these factors contribute to the variability in responses to
      statin treatment. Fifty-three AD patients had measurement of plasma levels of 24S
      hydroxycholesterol, plasma and lipoprotein cholesterol and genotyping of CYP46
      and apo E. Thirty-nine of the subjects subsequently participated in a statin
      trial for 6 weeks, and had a repetition of the baseline measurements. Baseline
      levels of 24S-hydroxycholesterol were higher in women than in men. There was a
      positive and significant correlation of plasma oxysterol levels with levels of
      total plasma cholesterol (women: r = .72, P < .0001; men: r = .47, P = .02) and
      non-HDL cholesterol (women: r = .68, P < .0001; men: r = 0.51, P = .01) (and LDL
      cholesterol) but not HDL cholesterol levels. There was no association of CYP46 or
      apo E polymorphisms with plasma levels of 24S-hydroxycholesterol. AD subjects
      treated with statins had a similar percent reduction in lathosterol, 24S
      hydroxycholesterol, total cholesterol and non-HDL (and LDL) cholesterol
      regardless of gender and polymorphisms of CYP46. Subjects with the 4/4
      polymorphism had less reduction in the ratios of 24S-hydroxycholesterol-LDL
      cholesterol. Women with AD had higher levels of plasma 24S-hydroxycholesterol
      levels than men. Women also showed a very strong correlation of plasma levels of
      24S-hydroxycholesterol-to-total and non-HDL cholesterol. This may suggest that
      the oxysterol may be an important marker of AD risk instead of total cholesterol,
      as suggested by others. Polymorphisms of CYP46 or apo E do not explain levels of
      oxysterol or non-HDL cholesterol or the responsiveness to statin treatment in
      this study.

PMID- 15975089
TI  - Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and
      is required for repair of DNA alkylation damage.
AB  - Members of the RecQ family of DNA helicases, mutated in several syndromes
      associated with cancer predisposition, are key regulators of genome stability.
      The Saccharomyces cerevisiae SLX4 gene is required for cell viability in the
      absence of Sgs1, the only yeast RecQ helicase. SLX4 encodes one subunit of the
      heterodimeric Slx1-Slx4 endonuclease, although its cellular function is not
      clear. Slx1-Slx4 was reported to preferentially cleave replication fork-like
      structures in vitro, and cells lacking SLX4 are hypersensitive to DNA alkylation
      damage. Here we report that Slx4 becomes phosphorylated in cells exposed to a
      wide range of genotoxins. Even though it has been proposed that the role of Slx4
      is restricted to S-phase, Slx4 phosphorylation is observed in cells arrested in
      G1 or G2 phases of the cell cycle, but not during an unperturbed cell cycle. Slx4
      phosphorylation is completely abolished in cells lacking the Mec1 and Tel1
      protein kinases, critical regulators of genome stability, but is barely affected
      in the absence of both Rad53 and Chk1 kinases. Finally we show that, whereas both
      Slx1 and Slx4 are dispensable for activation of cell-cycle checkpoints, Slx4, but
      not Slx1, is required for repair of DNA alkylation damage in both aynchronously
      growing cells and in G2-phase-arrested cells. These results reveal Slx4 as a new
      target of the Mec1/Tel1 kinases, with a crucial role in DNA repair that is not
      restricted to the processing of stalled replisomes.

PMID- 15975090
TI  - Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase
      components, Pen-2 and nicastrin.
AB  - Mutations in presenilin proteins (PS1 and PS2) lead to early-onset Alzheimer's
      disease. PS proteins are endoproteolytically cleaved into two main fragments: the
      NTF (PS N-terminal fragment) and the CTF (PS C-terminal fragment). The two
      fragments are believed to constitute the core catalytic enzyme activity called
      gamma-secretase, which is responsible for cleaving beta-amyloid precursor protein
      to release Abeta. Thus, studying factors that modulate PS fragment levels could
      provide important information about gamma-secretase. Previously, we demonstrated
      that the protein, ubiquilin-1, interacts both in vivo and in vitro with PS and
      that overexpression of ubiquilin-1 or -2 leads to increased accumulation of full
      length PS proteins. Using wild-type HEK-293 cells (human embryonic kidney 293
      cells) and PS-inducible cells, we now show that overexpression of either
      ubiquilin-1 or -2 decreases the PS NTF and CTF levels. Conversely, siRNA (small
      interfering RNA)-mediated knockdown of ubiquilin-1 and -2 proteins increased the
      PS NTF and CTF levels. We considered that ubiquilin might alter PS fragment
      accumulation by acting as a shuttle factor escorting PS fragments to the
      proteasome for degradation. However, through proteasome inhibition studies, we
      show that this does not occur. Instead, our results suggest that ubiquilin
      regulates PS fragment production. We also examined whether other components of
      the gamma-secretase complex are affected by ubiquilin expression. Interestingly,
      overexpression of ubiquilin resulted in a decrease in Pen-2 and nicastrin levels,
      two essential components of the gamma-secretase complex. In contrast, knockdown
      of ubiquilin-1 and -2 protein expression by RNAi (RNA interference) increased Pen
      2 and nicastrin levels. Finally, we show that inhibition of the proteasome
      results in decreased PS fragment production and that reversal of proteasome
      inhibition restores PS fragment production, suggesting that the proteasome may be
      involved in PS endoproteolysis. These studies implicate ubiquilin as an important
      factor in regulating PS biogenesis and metabolism.

PMID- 15975091
TI  - Generation of protein kinase Ck1alpha mutants which discriminate between
      canonical and non-canonical substrates.
AB  - Protein kinase CK1 denotes a family of pleiotropic serine/threonine protein
      kinases implicated in a variety of cellular functions. Typically, CK1 acts as a
      'phosphate-directed' kinase whose targeting is primed by a single phosphorylated
      side chain at position n-3 or n-4 relative to serine/threonine, but increasing
      evidence is accumulating that CK1 can also engage some of its substrates at sites
      that do not conform to this canonical consensus. In the present paper, we show
      that CK1a phosphorylates with the same efficiency phosphopeptides primed by a
      phosphoserine residue at either n-3 [pS(-3)] or n-4 [pS(-4)] positions. The
      phosphorylation efficiency of the pS(-4) peptide, and to a lesser extent that of
      the pS(-3) peptide, is impaired by the triple mutation of the lysine residues in
      the K229KQK232 stretch to alanine residues, promoting 40-fold and 6-fold
      increases of Km respectively. In both cases, the individual mutation of Lys232 is
      as detrimental as the triple mutation. A kinetic alanine-scan analysis with a
      series of substituted peptide substrates in which the priming phosphoserine
      residue was effectively replaced by a cluster of four aspartate residues was also
      consistent with a crucial role of Lys232 in the recognition of the acidic
      determinant at position n-4. In sharp contrast, the phosphorylation of b-catenin
      and of a peptide including the non-canonical b-catenin site (Ser45) lacking
      acidic/phosphorylated determinants upstream is not significantly affected by
      mutations in the KKQK stretch. These data provide a molecular insight into the
      structural features that underlie the site specificity of CK1a and disclose the
      possibility of developing strategies for the preferential targeting of subsets of
      CK1 substrates.

PMID- 15975092
TI  - Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1
      during cell spreading and migration.
AB  - In addition to tyrosine sites, FAK (focal adhesion kinase) is phosphorylated on
      multiple serine residues. In the present study, the regulation of two of these
      sites, Ser-722 (S1) and Ser-911 (S4), was investigated. Phosphorylation of S1
      (but not S4) decreased in resuspended cells, and recovered during spreading on
      fibronectin, indicating adhesion-dependent regulation. GSK3 (glycogen synthase
      kinase 3) inhibitors decreased S1 phosphorylation, and siRNA (short interfering
      RNA) silencing indicated further the involvement of GSK3beta. Furthermore,
      GSK3beta was found to become activated during cell spreading on fibronectin, and
      to physically associate with FAK. S1 phosphorylation was observed to decrease in
      wounded cell monolayers, while GSK3beta underwent inactivation and later was
      observed to increase to the original level within 24 h. Direct phosphorylation of
      S1, requiring pre-phosphorylation of Ser-726 in the +4 position, was demonstrated
      using purified GSK3 and a synthetic peptide containing FAK residues 714-730. An
      inhibitory role for S1 phosphorylation in FAK signalling was indicated by
      findings that both alanine substitution for S1 and dephosphorylation of S1 by PP1
      (serine/threonine protein phosphatase type-1) resulted in an increase in FAK
      kinase activity; likewise, this role was also shown by cell treatment with the
      GSK3 inhibitor LiCl. The inhibitory role was confirmed by the finding that cells
      expressing FAK with alanine substitution for S1 displayed improved cell spreading
      and faster migration in wound-healing and trans-well assays. Finally, the finding
      that S1 phosphorylation increased in cells treated with the PP1 inhibitor okadaic
      acid indicated targeting of this site by PP1. These results indicate an
      additional mechanism for regulation of FAK activity during cell spreading and
      migration, involving Ser-722 phosphorylation modulated through the competing
      actions of GSK3beta and PP1.

PMID- 15975093
TI  - Promiscuous interaction of SNAP-25 with all plasma membrane syntaxins in a
      neuroendocrine cell.
AB  - SNAP-25 (25 kDa synaptosome-associated protein) is found in cells that release
      neurotransmitters and hormones, and plays a central role in the fusion of
      secretory vesicles with the plasma membrane. SNAP-25 has been shown to interact
      specifically with syntaxin 1, a 35 kDa membrane protein, to mediate the fusion
      process. Here, we investigated whether other known syntaxin isoforms found at the
      plasma membrane can serve as binding partners for SNAP-25 in vivo. In our
      analysis, we employed rat phaeochromocytoma PC12 cells that are often used as a
      model of neuronal functions. We now show that these cells contain large amounts
      of SNAP-25, which interacts not only with syntaxin 1, but also with ubiquitous
      syntaxins 2, 3 and 4. The plasma membrane syntaxins appear to occupy
      complementary domains at the plasma membrane. In defined reactions, the
      ubiquitous plasma membrane syntaxin isoforms, when in binary complexes with SNAP
      25, readily bound vesicular synaptobrevin to form SDS-resistant SNARE (soluble N
      ethylmaleimide-sensitive fusion protein attachment protein receptor) complexes
      implicated in membrane fusion. However, vesicular synaptotagmin and cytosolic
      complexin, both implicated in the fusion process, exhibited differential ability
      to interact with the SNARE complexes formed by syntaxins 1-4, suggesting that the
      plasma membrane syntaxins may mediate vesicle fusion events with different
      properties.

PMID- 15975094
TI  - Nutrition in patients with Type 2 diabetes: are low-carbohydrate diets effective,
      safe or desirable?
AB  - Low-carbohydrate diets have been around for over 100 years. They have become very
      popular recently but the scientific basis for their use remains to be fully
      established. This article reviews the recent trials that have been published and
      also what is known about the effects of low-carbohydrate, high-protein diets on
      energy expenditure and body composition. Although many controversies remain,
      there is now mounting evidence that these diets can lead to effective weight loss
      and may thus be a useful intervention for patients who have, or are at risk of,
      diabetes. The practical aspects of using these diets as a short- to medium-term
      intervention are discussed.

PMID- 15975095
TI  - Screening for diabetes in Indigenous populations using glycated haemoglobin:
      sensitivity, specificity, post-test likelihood and risk of disease.
AB  - AIMS: Screening for diabetes using glycated haemoglobin (HbA1c) offers potential
      advantages over fasting glucose or oral glucose tolerance testing. Current
      recommendations advise against the use of HbA1c for screening but test properties
      may vary systematically across populations, according to the diabetes prevalence
      and risk. We aimed to: (i) characterize the properties of test cut-offs of HbA1c
      for diagnosis of diabetes relative to a diagnosis based on a fasting plasma
      glucose concentration of 7.0 mmol/l for high-risk Indigenous populations; and
      (ii) examine test properties across a range of diabetes prevalence from 5 to 30%.
      METHODS: Data were collected from Aboriginal and Torres Strait Islander
      communities in Australia and a Canadian First Nations community (diabetes
      prevalence 12-22%) in the course of diabetes diagnostic and risk factor screening
      programmes (n = 431). Screening test properties were analyzed for the range of
      HbA1c observed (3-12.9%). RESULTS: In separate and pooled analyses, a HbA1c cut
      point of 7.0% proved the optimal limit for classifying diabetes, with summary
      analysis results of sensitivity = 73 (56-86)%, specificity = 98 (96-99)%, overall
      agreement (Youden's index) = 0.71, and positive predictive value (for an overall
      prevalence of 18%) = 88%. For diabetes prevalence from 5 to 30% the post-test
      likelihood of having diabetes given HbA1c = 7.0% (positive predictive value)
      ranged from 62.7 to 93.2%; for HbA1c < 7.0%, the post-test likelihood of having
      diabetes ranged from 4.5 to 27.7%. CONCLUSIONS: The results converge with
      research on the likelihood of diabetes complications in supporting a HbA1c cut
      off of 7.0% in screening for diabetes in epidemiological research. Glycated
      haemoglobin has potential utility in screening for diabetes in high-risk
      populations.

PMID- 15975096
TI  - An assessment of the coverage of a district-wide diabetic retinopathy screening
      service.
AB  - AIMS: To assess the coverage of the diabetes retinopathy screening service (DRSS)
      in North Staffordshire, to identify patient characteristies associated with non
      attendance and to assess the proportion of patients with diabetic retinopathy who
      achieved glycaemic and blood pressure (BP) control targets. METHODS: Data for all
      patients who underwent annual retinal screening between 1 May 2000 and 30 April
      2001 were obtained from the North Staffordshire Diabetes Register. Age, gender,
      ethnicity, socio-economic status, type and duration of diabetes were compared
      between patients who underwent eye screening and those who did not. Frequencies
      of patients who achieved glycaemic and BP targets in these groups of patients
      were compared to the remaining patients. RESULTS: 5646 of the 11682 (48%)
      patients on the diabetes register underwent retinal screening during the year.
      Patients with Type 2 diabetes, older patients, patients belonging to ethnic
      minorities and those wholly managed in primary care were less likely to attend
      for eye screening (P < 0.05 for all groups) with ethnic minority or primary care
      management demonstrating independent influence (P < 0.001). The percentage of
      patients with retinopathy achieving HbA1c and systolic BP targets was
      significantly lower than in their unaffected counterparts (chi2 = 63, P < 0.001
      and chi2 = 71, P < 0.001 respectively). CONCLUSIONS: The efficacy of the DRSS in
      North Staffordshire is low and might be improved by targeting specific patient
      groups. Glycaemic control and systolic BP control needs to be improved in
      patients with diabetic retinopathy.

PMID- 15975097
TI  - Indications and efficacy of continuous subcutaneous insulin infusion (CSII)
      therapy in Type 1 diabetes mellitus: a clinical audit in a specialist service.
AB  - AIM: To determine if current guidelines correctly identify patients who will
      benefit from continuous subcutaneous insulin infusion (CSII) therapy by comparing
      outcomes between Type 1 diabetic patients with recurrent severe hypoglycaemia
      (SH) indications with those without; and between patients without and with
      classic contraindications to CSII managed in a single multidisciplinary pump
      clinic. METHODS: Changes in biomedical outcomes [glycated haemoglobin (HbA1c),
      hypoglycaemia, diabetic ketoacidosis (DKA) rates], from before CSII to the end of
      the study (median duration 20.5 months, range 1-192), were analysed
      retrospectively from data collected from notes and interviews of 40 patients.
      Quality of life was assessed by three validated questionnaires at study end (33
      patients). RESULTS: Twenty-five out of forty patients were started for reasons
      other than SH and 15 out of 40 had contraindications to CSII. Overall, CSII was
      associated with a reduction in HbA1c (9.6 +/- 2.7% to 8.3 +/- 1.2%, P = 0.011),
      SH (6.45 +/- 16.15/year to 0.34 +/- 1.01/year, P = 0.034) and DKA (1.83 +/-
      4.48/year to 0.27 +/- 1.12/year, P = 0.036). The fall in SH was greater for
      patients started for SH (P < 0.001). However, only patients started for other
      indications showed a fall in HbA1c (P = 0.001). The fall in DKA rate was greater
      in patients with contraindications (P = 0.042), and they did not lose the other
      benefits of CSII therapy, including quality of life. CONCLUSIONS: In the setting
      of a specialist multidisciplinary service, CSII can be an effective and safe
      therapy. It confers benefit outside the setting of severe hypoglycaemia and can
      confer benefit in some patients with classic contraindications. This questions
      the validity of criteria that may exclude these patients in such a service.

PMID- 15975098
TI  - Comparison of three multiple injection regimens for Type 1 diabetes: morning plus
      dinner or bedtime administration of insulin detemir vs. morning plus bedtime NPH
      insulin.
AB  - AIMS: This trial investigated the efficacy and safety of two different
      administration-time regimens with insulin detemir (IDet) to that of a
      conventional basal insulin regimen with NPH insulin (NPH). METHODS: This
      multinational, 16-week, open, parallel group trial included 400 people with Type
      1 diabetes mellitus (DM) randomized to IDet either morning and before dinner
      (IDetmorn+din) or morning and bedtime (IDetmorn+bed), or to NPH morning and
      bedtime (NPHmorn+bed), all in combination with mealtime insulin aspart (IAsp).
      RESULTS: HbA1c was comparable between the three groups after 16 weeks (P = 0.64),
      with reductions of 0.39-0.49% points. Lower fasting plasma glucose (FPG) was
      observed with IDetmorn+din and IDetmorn+bed compared with NPHmorn+bed (9.8 and
      9.1 vs. 11.1 mmol/l, P = 0.006), whereas the IDet groups did not differ (P =
      0.15). Within-person variation in self-measured FPG was significantly lower for
      both IDet regimens (sd IDetmorn+din 2.5, IDetmorn+bed 2.6 mmol/l) than for
      NPHmorn+bed (sd 3.1 mmol/l, P < 0.001), but was comparable between the IDet
      groups (P = 0.48). Ten-point plasma glucose profiles were lower between dinner
      and breakfast in the IDetmorn+din group (P = 0.043), compared with the two other
      groups. Risk of overall and nocturnal hypoglycaemia was similar for the three
      groups. Lower mean bodyweight was observed with IDet compared with NPH after 16
      weeks (difference: (IDetmorn+din)-1.3 kg, P < 0.001, (IDetmorn+bed)-0.6 kg, P =
      0.050). CONCLUSIONS: Both IDet regimens were well tolerated and provided lower
      and less variable glucose levels with no, or less, weight gain than NPH at
      comparable HbA1c. IDet can be administered either at dinner or bedtime, with
      similar glycaemic control according to the need of the individual person.

PMID- 15975099
TI  - Reproducibility and reliability of hypoglycaemic episodes recorded with
      Continuous Glucose Monitoring System (CGMS) in daily life.
AB  - AIM: Continuous glucose monitoring may reveal episodes of unrecognized
      hypoglycaemia. We evaluated reproducibility and reliability of hypoglycaemic
      episodes recorded in daily life by the Medtronic MiniMed Continuous Glucose
      Monitoring System (CGMS). METHODS: Twenty-nine adult patients with Type 1
      diabetes underwent 6 days of continuous subcutaneous glucose monitoring, applying
      one CGMS on each side of the abdomen. Blood glucose was measured by HemoCue B
      Glucose Analyzers six times daily and two different 4-point calibration sets were
      generated (set A and B). Using these calibration sets, CGMS raw data were
      recalibrated generating four different CGMS data sets [left-A (left side of
      abdomen, calibration set A), left-B, right-A and right-B]. Agreement between CGMS
      data sets was evaluated during hypoglycaemic events, comparing CGMS readings =
      2.2 mmol/l with nadir values from corresponding CGMS data sets. CGMS readings
      were also compared with independent self-monitored blood glucose (SMBG) values.
      RESULTS: With hypoglycaemia (CGMS readings = 2.2 mmol/l) in calibration set left
      A, values below 3.5 mmol/l were present in 99% (95% CI: 95-100%) of samples in
      left-B, 91% (95% CI: 84-96%) of samples in right-A, and 90% (95% CI: 83-95%) of
      samples in right B. In 84% of these episodes (95% CI: 59-96%) independent SMBG
      values were below 3.5 mmol/l. Difference in duration was observed with a median
      difference of 20 min; (left-A vs. right-B). CONCLUSION: Hypoglycaemic episodes
      recorded by CGMS are reproducible and agreement with independent SMBG values is
      acceptable for retrospective recording of hypoglycaemic events with CGMS.

PMID- 15975100
TI  - Association of C-reactive protein with body fat, diabetes and coronary artery
      disease in Asian Indians: the Chennai Urban Rural Epidemiology Study (CURES-6).
AB  - OBJECTIVE: The aim of the study was to determine the association of high
      sensitivity C-reactive protein (hs-CRP) with body fat, diabetes and coronary
      artery disease (CAD) in an urban south Indian population. DESIGN: The study was
      conducted on 150 subjects selected from the Chennai Urban Rural Epidemiology
      Study (CURES), an ongoing population-based study on a representative population
      of Chennai (formerly Madras). Group 1 comprised of non-diabetic subjects without
      CAD (n = 50). Type 2 diabetic subjects without CAD formed Group 2 (n = 50); Group
      3 comprised of Type 2 diabetic subjects with CAD (n = 50). CAD was diagnosed
      based on electrocardiographic (ECG) changes suggestive of ST segment depression
      and/or Q wave changes using appropriate Minnesota codes. All study subjects were
      non-smokers, and had no infectious or inflammatory diseases. The plasma levels of
      hs-CRP were measured using a highly sensitive nephelometric assay. Body fat was
      calculated using Siri's formula using skin fold measurements. RESULTS: Diabetic
      subjects with (2.89 mg/l) and without (2.25 mg/l) CAD had significantly higher hs
      CRP levels compared with non-diabetic subjects without CAD (0.99 mg/l, P <
      0.001). hs-CRP values increased with increases in tertiles of body fat (ANOVAP <
      0.001) and HbA1c (ANOVAP < 0.001). Multiple logistic regression analysis revealed
      hs-CRP to be strongly associated with CAD (OR: 1.649, P = 0.040) and diabetes
      (OR: 2.264, P = 0.008) even after adjusting for age and gender. Regression
      analysis also revealed body fat to be strongly associated with diabetes and CAD
      even after adjusting for age and gender (P < 0.001). hs-CRP influenced this
      association for diabetes but not for CAD. CONCLUSION: hs-CRP showed a strong
      association with CAD and diabetes, even after adjusting for age and gender. The
      association of body fat with diabetes seems to be mediated through hs-CRP.
      However, hs-CRP does not appear to mediate the relationship between body fat and
      CAD.

PMID- 15975101
TI  - Impaired vascular function during short-term poor glycaemic control in Type 1
      diabetic patients.
AB  - AIM: To study the effects of short-term poor glycaemic control on vascular
      function in Type 1 diabetic patients. METHODS: Ten Type 1 diabetic patients, with
      diabetes duration of less than 10 years and normal urinary albumin excretion and
      ophthalmoscopy, were studied. All patients were examined after 48 h of good vs.
      poor glycaemic control within a 3-week period. Blood glucose was measured seven
      times daily for 2 days before each examination. External ultrasound was used to
      measure the dilatory response of the brachial artery to post-ischaemic increased
      blood flow (endothelium-dependent dilation) and to nitroglycerin (endothelium
      independent dilation). Plasma concentration of von Willebrand factor antigen,
      adhesion molecules, vascular endothelial growth factor, homocystein and
      cholesterol were also measured. RESULTS: The median blood glucose levels in the
      48 h before the examinations were [median (range), good vs. poor control]: 6.3
      (5.0-7.6) vs. 15.9 (11.3-17.8) (mmol/l). The flow-associated vasodilation (% of
      baseline) was reduced during poor control: 102.7 (94.7-110.8) vs. 104.0 (99.6
      118.5) (P < 0.05) as were the nitroglycerin-induced dilation (% of baseline):
      114.5 (103.3-127.9) vs. 120.2 (106.8-148.0) (P < 0.05). P-von Willebrand factor
      antigen was high during poor control (kIU/l): 1.14 (0.73-1.84) vs. 0.86 (0.72
      1.39) (P < 0.05) and so was P-vascular endothelial growth factor (ng/l): 288 (133
      773) vs. 254 (90-383) (P < 0.05). CONCLUSIONS: Short-term (48 h) hyperglycaemia
      in Type 1 diabetic patients may disturb vascular function, possibly mediated
      through smooth muscle cell dysfunction as well as endothelial dysfunction. We
      suggest that prolonged and repeated episodes of hyperglycaemia could possibly
      lead to permanent vascular dysfunction and thereby development and progression of
      vascular complications in diabetes.

PMID- 15975102
TI  - Lower plasma triglycerides are associated with increased need for insulin
      requirement in poorly controlled Type 2 diabetic patients.
AB  - AIMS: To identify factors associated with insulin requirement in Type 2 diabetic
      patients, and to examine the significance of a normal plasma triglyceride level.
      METHODS: One hundred and three poorly controlled (HbA1c = 9.4 +/- 1.9%) Type 2
      diabetic patients initially not treated with insulin were followed up for 5
      years. Insulin was administered if HbA1c > 8% despite maximal oral anti-diabetic
      treatment and bodyweight control. Variables were compared between insulin
      requiring and non-insulin-treated patients using unpaired t-tests. The outcomes
      of initially normotriglyceridaemic (< 1.7 mmol/l) and hypertriglyceridaemic
      patients were compared using unpaired t-tests, and a survival analysis (Cox
      proportional hazards model). RESULTS: Sixty-three patients were transferred to
      insulin. They were 5 years older (P = 0.004), with a 3-year longer duration of
      their diabetes (P = 0.03), a 1.2% higher HbA1c (P = 0.002), and 50% lower
      triglyceride levels (P = 0.02) than the others. The survival analysis showed that
      a long duration of diabetes, a high HbA1c, and a normal triglyceride level were
      associated with the need for insulin; the effect of normotriglyceridaemia was
      significant in the most poorly controlled (HbA1c > 9.5%) patients (relative risk:
      2.35, 95% confidence interval: 1.16-5.52, P = 0.016). The 46
      normotriglyceridaemic patients were leaner (P = 0.0004) and had lower C-peptide
      levels (P = 0.0008) than the others. Despite similar diabetes duration and HBA1c,
      more were transferred to insulin (normotriglyceridaemic: 71%,
      hypertriglyceridaemic: 52%, P = 0.03). CONCLUSION: A normal triglyceride level is
      associated with a need for insulin in poorly controlled Type 2 diabetes.

PMID- 15975103
TI  - ADVANCE--Action in Diabetes and Vascular Disease: patient recruitment and
      characteristics of the study population at baseline.
AB  - AIMS: The primary aim of ADVANCE is to determine the effects on macrovascular and
      microvascular disease of blood pressure lowering (with an ACE inhibitor-diuretic
      combination), irrespective of initial blood pressure level; and of intensive
      glucose lowering, in high-risk individuals with Type 2 diabetes. METHODS: The
      study is a 2 x 2 factorial randomized controlled trial. Following 6 weeks on
      active perindopril-indapamide combination, eligible participants were randomized
      to perindopril/indapamide (initially 2.0/0.625 mg daily, increasing to 4.0/1.25
      mg daily after 3 months) or matching placebo; and to an intensive gliclazide MR
      based glucose control regimen aiming for a haemoglobin A1c (HbA1c) value of 6.5%
      or lower, or local standard therapy. The study is being conducted in 215 centres
      in 20 countries within Australasia, Asia, Europe and North America. RESULTS:
      Recruitment commenced in June 2001 and was completed in March 2003, with the
      inclusion of 11,140 randomized participants. Fifty-seven per cent of participants
      are male and the mean age at baseline was 66 years. On average, the diagnosis of
      diabetes was made 8 years before study entry. At baseline 32 and 10% of patients
      had a history of macrovascular and microvascular disease, respectively. The mean
      blood pressure at baseline was 145/81 mmHg; the mean HbA1c concentration was
      7.5%. While blood pressure and HbA1c values were broadly similar, certain
      characteristics of randomized participants varied between countries. CONCLUSIONS:
      With successful worldwide recruitment completed, ADVANCE should provide reliable
      and broadly generalizable results on the effects of routine blood pressure
      lowering and intensive glucose control in high-risk individuals with Type 2
      diabetes.

PMID- 15975104
TI  - Prospective screening for biopsy proven coeliac disease, autoimmunity and
      malabsorption markers in Belgian subjects with Type 1 diabetes.
AB  - AIMS: To determine prospectively the prevalence of biopsy proven coeliac disease
      (CD) in an adult Type 1 diabetic population from Belgium with regards to
      associated auto-immunity and malabsorption. METHODS AND RESULTS: Determination in
      400 Type 1 diabetic patients of serum anti-endomysial and/or anti
      transglutaminase auto-antibodies. All subjects with abnormal serology underwent
      an intestinal biopsy. Ten patients (2.5%) had positive antibodies. Diagnosis of
      CD was confirmed by an intestinal biopsy. Eight patients were symptom-free,
      although laboratory findings suggesting malabsorption were prominent in the
      presence of CD [microcytic anaemia, iron and folate deficiencies, low levels of
      25(OH)vitamin D3, calcium and cholesterol]. Other auto-immune conditions,
      especially vitiligo, were found in patients with CD. CONCLUSIONS: Asymptomatic
      coeliac disease occurs frequently in adult Type 1 diabetic patients, and is often
      associated with subclinical malabsorption. Screening should be part of routine
      evaluation, to implement life-long dietary gluten avoidance.

PMID- 15975105
TI  - Physical activity and energy intake in adolescent girls with Type 1 diabetes.
AB  - AIMS: Girls with Type 1 diabetes often gain excessive weight during puberty. The
      aims of this study were to compare objectively assessed physical activity and
      energy intake in girls with Type 1 diabetes with those in healthy age-matched
      controls. METHODS: This prospective cohort study comprised 26 girls with Type 1
      diabetes and 49 control girls. The mean age of the diabetic girls was 15.7 +/-
      2.1 years and that of the control girls 15.8 +/- 2.1 years. In the diabetic
      group, mean haemoglobin A1c was 7.6 +/- 1.4% and daily insulin dosage was 1.1 +/-
      0.3 U/kg. Physical activity was measured during 7 consecutive days with a
      uniaxial accelerometer, and energy intake was assessed concurrently with a 7-day
      food diary. RESULTS: There was a tendency towards lower total amount of physical
      activity in the diabetes group but the difference between the study groups did
      not reach statistical significance (Diabetes: 464 +/- 123 counts/min/day;
      CONTROLS: 523 +/- 138 counts/min/day; P = 0.06). No difference was found between
      the groups regarding total energy intake (Diabetes: 8.5 +/- 1.8 MJ/day; CONTROLS:
      8.4 +/- 2.6 MJ/day). The carbohydrate intake was lower and the protein and fibre
      intakes were higher in girls with diabetes. No association was observed between
      physical activity, energy intake and HbA1c. CONCLUSIONS: In this prospective
      cohort study, we found a tendency towards lower physical activity but no
      differences in energy intake between girls with Type 1 diabetes and age-matched
      controls. Larger studies are needed to further explore the importance of the
      total amount of physical activity for excessive weight gain in adolescent girls
      with Type 1 diabetes.

PMID- 15975106
TI  - Self-monitoring of blood glucose in non-insulin-treated diabetic patients: a
      longitudinal evaluation of its impact on metabolic control.
AB  - AIMS: In the framework of a nationwide outcomes research programme, we assessed
      the impact of self-monitoring of blood glucose (SMBG) on metabolic control over 3
      years in patients with Type 2 diabetes mellitus (DM2) not treated with insulin.
      METHODS: The study involved 1896 patients who completed, at 6-month intervals for
      3 years, a questionnaire investigating SMBG practice. Clinical information was
      collected by participating clinicians at the same time intervals. The predictive
      value of SMBG frequency on long-term metabolic control was estimated using
      multilevel analysis. The impact of SMBG on metabolic control was also evaluated
      in distinct and homogeneous subgroups of patients showing different likelihood of
      performing SMBG, identified using a tree-growing technique (RECPAM). RESULTS:
      Overall, 22% of the patients were on diet alone and 78% were treated with oral
      agents; 41% practiced SMBG > or = 1/week (10.3% > or = 1/day). The analysis of
      metabolic control according to the frequency of SMBG failed to show any
      significant impact of this practice on HbA1c levels over 3 years. Similarly,
      changes in SMBG frequency during the study were not related to significant
      changes in HbA1c levels. RECPAM analysis led to the identification of eight
      classes, characterized by substantial differences in the likelihood of performing
      SMBG with a frequency of at least 1/week. Nevertheless, in none of the RECPAM
      classes identified, did SMBG predict a better metabolic control over 3 years of
      follow-up. In those RECPAM classes indicating that SMBG was mainly performed to
      avoid hypoglycaemic episodes, SMBG was associated with a decrease in the
      frequency of hypoglycaemic episodes during the study. CONCLUSIONS: In a large
      sample of non-insulin-treated Type 2 diabetic patients, the performance and
      frequency of SMBG did not predict better metabolic control over 3 years. We could
      not identify any specific subgroups of patients for whom SMBG practice was
      associated with lower HbA1c levels during the study.

PMID- 15975107
TI  - Does metformin decrease blood pressure in patients with Type 2 diabetes
      intensively treated with insulin?
AB  - AIMS: We investigated in a double-blind study whether metformin reduces blood
      pressure (BP) in patients with Type 2 diabetes intensively treated with insulin.
      METHODS: A total of 220 patients with Type 2 diabetes were asked to undergo 24-h
      ambulatory BP monitoring (24-h ABPM). One hundred and eighty-two gave informed
      consent. Eighty-nine were randomized to metformin and 93 to placebo. Thirty-five
      subjects dropped out (13 placebo, 22 metformin users); 147 patients underwent a
      second 24-h ABPM, 16 weeks after randomization. RESULTS: Systolic BP (SBP),
      diastolic BP (DBP), pulse BP (PP), mean BP (MP) and heart rate (HR) were measured
      as office BP measurements and as 24-h ABPM for 24-h, day and night. Office BP
      measurements did not differ significantly between the placebo- and metformin
      treated groups for any BP measure, but showed a non-significant trend for SBP
      reduction with metformin use (mean baseline-adjusted difference, metformin minus
      placebo: -4.2 mmHg, 95% CI, -9.9 to +1.5; P = 0.15). The baseline-adjusted
      differences of the ambulatory measurements were -0.2 mmHg (95% CI, -2.9 to +2.6)
      for the 24-h SBP, and +1.1 mmHg (95% CI, -0.7 to +2.8) for the 24-h DBP. On the
      whole, BP differences between metformin- and placebo-treated groups were not
      statistically significant. The only significant difference was for night-time PP
      (baseline-adjusted difference: -2.2 mmHg; 95% CI, -4.2 to -0.2). These results
      were not different after adjustment for age and diabetes duration, or for
      (changes in) body mass index, glycated haemoglobin, insulin dose or plasma
      homocysteine. CONCLUSION: Metformin does not significantly affect BP in patients
      with Type 2 diabetes intensively treated with insulin.

PMID- 15975108
TI  - Fetal erythrocyte membrane lipids modification: preliminary observation of an
      early sign of compromised insulin sensitivity in offspring of gestational
      diabetic women.
AB  - AIMS: Intrauterine exposure to diabetes is a significant determinant of the
      development of obesity and early onset of Type 2 diabetes mellitus in the
      offspring. Both conditions are characterized by insulin resistance and the latter
      is associated with reduced membrane arachidonic and docosahexaenoic acids. Hence,
      we investigated if the membrane arachidonic and docosahexaenoic acids are
      depressed in the cord blood of babies born to women with gestational diabetes.
      METHODS: Cord (fetal) and maternal blood were obtained at delivery from control
      subjects (n = 33) and women with gestational diabetes (n = 40) and analysed for
      plasma triglycerides and cholinephosphoglycerides, and erythrocyte choline- and
      ethanolaminephosphoglycerides fatty acids. RESULTS: Babies of gestational
      diabetic mothers had reduced docosahexaenoic acid in the plasma (5.9 +/- 1.4 vs.
      7.1 +/- 2.0, P < 0.01) and erythrocyte (4.0 +/- 2.2 vs. 5.4 +/- 2.9, P < 0.05)
      cholinephosphoglycerides. Moreover, the total omega-6 and omega-3 fatty acids of
      the erythrocyte cholinephosphoglycerides were significantly lower (P < 0.05) in
      these babies. A similar trend was observed in plasma triglycerides and
      erythrocyte ethanolaminephosphoglycerides. The maternal plasma triglycerides and
      erythrocyte ethanolaminephosphoglycerides fatty acids profile were not different
      between the two groups. However, there was a reduction in arachidonic acid and
      total omega-6 fatty acids in the erythrocyte cholinephosphoglycerides of the
      gestational diabetic women. CONCLUSION: The altered plasma and erythrocyte fatty
      acids in the cord blood of babies born to women with gestational diabetes
      suggests a perturbation in the maternal-fetal nutrient transport and/or fetal
      lipid metabolism.

PMID- 15975109
TI  - The association of birthweight and contemporary size with insulin resistance
      among children from Estonia and Denmark: findings from the European Youth Heart
      Study.
AB  - OBJECTIVES: To assess the associations of birthweight, contemporary body mass
      index and height with insulin resistance in children. DESIGN: Cross-sectional
      study. PARTICIPANTS: From Estonia (n = 1174) and Denmark (n = 1018), 2192 school
      children aged 9 and 15 years were randomly selected. MAIN OUTCOMES: Insulin
      resistance (homeostasis model assessment), triglyceride levels, high-density
      lipoprotein cholesterol and systolic blood pressure. RESULTS: There was an
      inverse association between birthweight and insulin resistance and a positive
      association between contemporary body mass index and insulin resistance. With
      adjustment for maternal and paternal educational level, income, smoking and body
      mass index, an increase of one unit of sex, age and country standardized body
      mass index z-score was associated with a 5% (95% CI: 2, 7%) increase in
      homeostasis model assessment (HOMA) score and a one-unit z-score increase in
      birthweight with a 2% (95% CI: 0, 5%) decrease in HOMA score. In the 9-year-old
      age group, height was positively associated with insulin resistance [for a one
      unit increase in height z-score HOMA score increased by 30% (95% CI: 14, 50%)],
      but in the 15-year-old age group there was no association between height and
      insulin resistance (4% (95% CI: -5, 14%), P for interaction with age group =
      0.001). For both ages, those in the lowest third of the birthweight distribution
      and highest third of the body mass index distribution were most insulin resistant
      and, among 9-year olds, those in the lowest third of the birthweight distribution
      and highest third of the height distribution were most insulin resistant.
      Birthweight was only inversely associated with systolic blood pressure when
      adjustment was made for either contemporary body mass index or height and there
      was no association between birthweight and high-density lipoprotein or
      triglyceride concentrations. CONCLUSIONS: Taken together, these results suggest
      that a slow intrauterine growth trajectory and/or a fast post-natal growth
      trajectory is associated with greater insulin resistance in childhood.

PMID- 15975110
TI  - Type 2 diabetes in rural and urban population: diverse prevalence and associated
      risk factors in Bangladesh.
AB  - AIMS: To describe differences in prevalence of Type 2 diabetes mellitus with its
      associated risk factors between rural and urban populations in Bangladesh.
      Diagnostic criteria [fasting blood glucose (FBG) and oral glucose tolerance tests
      (OGTT)] were compared and reviewed for both populations. METHODS: A total of 1555
      subjects from urban and 4757 from rural communities (age > or = 20 years) with
      similar cultural and ethnic backgrounds were randomly selected in a cross
      sectional survey. FBG values were determined from all and 2-h post-glucose
      capillary blood samples were determined after a 75-g oral glucose load for a
      selected number (urban 476, rural 1046). RESULTS: A higher prevalence of diabetes
      was found in urban (8.1%) compared with rural populations (2.3%). Age, sex and
      waist-to-hip ratio for men were significant risk factors for both urban and rural
      subjects following fasting and 2-h post-glucose values adjusted for a number of
      confounding variables. Poor agreement was observed between FBG and OGTT for both
      urban (kappa 0.41) and rural (kappa 0.40) areas. CONCLUSIONS: A higher prevalence
      of diabetes mellitus (DM) in the urban population was observed compared with
      rural subjects despite similar body mass indexes (BMI). Differences in obesity,
      waist/hip ratio or hypertension failed to explain the increasing occurrence of
      T2DM in the urban population.

PMID- 15975111
TI  - Management of incidental hyperglycaemia in acute medical emergencies.
AB  - AIMS: To assess whether compliance with management guidelines for hyperglycaemia
      in acute medical emergencies was affected by prior diagnosis of diabetes, and to
      assess the effect of an educational campaign upon management. METHODS:
      Prospective study of management of adult patients admitted to an acute medical
      admissions unit in 2002, with repeat in 2003 after an educational campaign.
      RESULTS: The management of 251 patients in 2002 and 357 patients in 2003 was
      examined. In patients with no prior diagnosis of diabetes, unsatisfactory
      management was observed in 60% compared with only 30% of those with known
      diabetes (P < 0.02). In 2003 these proportions fell to 46 and 16%, respectively,
      but remained significantly different (P < 0.02). Overall, 30 of 70 (42.9%)
      patients with hyperglycaemia were managed strictly according to the guidelines in
      2002 compared with 33 out of 59 (55.9%) in 2003 (P = 0.14). Satisfactory
      management was delivered in 55.7% in 2002 and 78% in 2003 (P < 0.01).
      CONCLUSIONS: The reluctance of doctors to manage incidental hyperglycaemia in
      acute medical admissions was especially common when the patient was not known to
      have diabetes. This was only modestly improved by an educational campaign, even
      though this group are known to have a greater response in terms of morbidity and
      mortality. Widespread debate of this issue is required to minimize morbidity and
      mortality due to hyperglycaemia.

PMID- 15975112
TI  - Depression in Croatian Type 2 diabetic patients: prevalence and risk factors. A
      Croatian survey from the European Depression in Diabetes (EDID) Research
      Consortium.
AB  - AIMS: To determine the prevalence rate of and risk factors for depression in
      Croatian Type 2 diabetic patients. METHODS: Depressive mood was examined in 384
      randomly selected outpatients with Type 2 diabetes. Center for Epidemiological
      Studies Depression Scale (CES-D) and Structured Clinical Interview for DSM-IV
      Axis I Disorders (SCID) were used to identify depressive disturbances. The groups
      with CES-D > or = 16 and < 16 were compared with respect to demographic,
      psychological and clinical characteristics. Regression analysis was used to
      determine risk factors for depression. RESULTS: Of the examined patients, 22% had
      CES-D scores > or = 16, and in 33% of them clinical depression was confirmed by
      the psychiatric interview. Depressed patients compared with the non-depressed
      ones reported more diabetes-related problems and poorer well-being (t = 6.71, P <
      0.001 and t = 11.98, P < 0.001, respectively). Multiple regression analysis
      indicated female gender, experienced support and the level of emotional well
      being to predict depression (R = 0.74, F = 15.3, P < 0.001). CONCLUSIONS: The
      obtained data indicate that the prevalence rate in Croatian Type 2 diabetic
      patients is comparable to findings from other cultural settings. Depressive
      symptoms can be predicted by psychological rather than disease-related variables.
      Psychological care for diabetic patients may be necessary to prevent depressive
      symptomatology.

PMID- 15975113
TI  - Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired
      insulin secretion.
AB  - AIMS: This study aimed to investigate if the previously observed association
      between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral
      glucose-induced serum insulin concentrations could be replicated in a large-scale
      population-based cohort of Danish whites. METHODS: The GLUT10 Ala206Thr
      polymorphism was genotyped in a case-control study of 880 Type 2 diabetic
      patients and 4372 glucose-tolerant control subjects. The latter group was also
      enrolled in an assessment of fasting and post-OGTT circulating levels of plasma
      glucose and serum insulin in relation to genotype. The variant was genotyped by
      analysis of PCR-generated primer extension by matrix-assisted laser
      desorption/ionization time-of-flight analysis. RESULTS: The Ala206Thr variant was
      equally frequent among Type 2 diabetic patients and glucose-tolerant subjects (P
      = 0.9) and there was no difference in the distribution of genotype groups (P =
      1.0). In the 4372 glucose-tolerant subjects there was no statistically
      significant association between the polymorphism and levels of fasting and post
      oral glucose tolerance test plasma glucose and serum insulin along with the
      insulinogenic index and the homeostasis model of assessment for insulin
      resistance and insulin secretion. Likewise, in an age-stratified subgroup
      comprising 1264 subjects, we observed no relationships between the GLUT10
      polymorphism and the selected metabolic features. CONCLUSIONS: The GLUT10
      Ala206Thr polymorphism is not associated with Type 2 diabetes in the Danish
      population. Furthermore, in the present large-scale cohort, the polymorphism does
      not associate with phenotypes such as fasting and oral glucose-induced levels of
      plasma glucose and serum insulin.

PMID- 15975114
TI  - No consistent association between birthweight and parental risk of diabetes and
      cardiovascular disease.
AB  - INTRODUCTION: The fetal insulin hypothesis proposes that the inverse relationship
      between birthweight and risk of diabetes and cardiovascular disease is partly as
      a result of inherited factors which influence the effect of insulin and insulin
      like growth factors. It has been proposed that an inverse relationship between
      birthweight and parental risk of diabetes and cardiovascular disease is evidence
      in support of this hypothesis. PATIENTS AND METHODS: Data from a prospective
      birth cohort study, followed up to age 50, was used to assess the relationship
      between birthweight and reported parental diabetes, hypertension, angina and
      stroke using logistic regression. RESULTS: Of the 832 cohort members traced at
      age 50, 574 (69%) returned questionnaires that included questions on parental
      illness. Complete data was available for 541 (94%) of these on maternal illness
      and for 531 (92%) on paternal illness. Birthweight, standardized for sex and
      gestational age and adjusted for social class at birth, was inversely associated
      with maternal stroke (odds ratio = 0.75, 95% confidence intervals 0.60-0.95).
      There were no other statistically significant associations between birthweight
      and risk of parental illness. DISCUSSION: We found little evidence of a
      consistent inverse relationship between birthweight and parental risk of diabetes
      or cardiovascular disease. This may be because of the quality of our data--which
      is limited by the problems of collecting robust data over two generations.

PMID- 15975115
TI  - Contribution of fasting and postprandial plasma glucose to HbA1c.

PMID- 15975116
TI  - Gender influences the impact of sickle cell trait on Type 2 diabetic
      complications.

PMID- 15975117
TI  - Diabetes and endocrinology as a career? A questionnaire survey of medical senior
      house officers.

PMID- 15975118
TI  - Malignant melanoma presenting as foot ulcer.

PMID- 15975119
TI  - Viruses and diabetes.

PMID- 15975120
TI  - Cognitive impairment following severe hypoglycaemia: response to Kubiak et al.

PMID- 15975125
TI  - The prevalence of signs and symptoms of temporomandibular disorders in very old
      subjects.
AB  - Previous studies on the prevalence of signs of temporomandibular disorders (TMD)
      in elderly people have used non-standardized and invalidated examination
      protocols. The prevalence of the different signs of TMD in this group is
      therefore still unclear. The aim of this study was to evaluate the prevalence of
      signs of TMD in subjects of advanced aged, using a standardized and validated
      examination protocol. Additionally, young subjects were examined as a control
      group. Fifty-eight old peoples' home inhabitants and 44 young subjects were
      examined using a standardized and validated examination protocol. Differences
      between the groups were assessed using Mann-Whitney U-test or t-test. Geriatric
      subjects more often exhibited objective symptoms of TMD (38% exhibited joint
      sounds on opening), but rarely suffered from pain (pain at rest: 0%, joint pain:
      0%, muscle pain: 12%). In contrast, young subjects rarely exhibited objective
      symptoms (joint sounds: 7%), but suffered more frequently from pain (facial: 7%,
      joint pain: 16%, muscle pain: 25%). The mandibular range of motion was higher in
      young subjects. Differences between the groups with respect to joint sounds,
      muscular palpation pain and mandibular range of motion were significant. Although
      older subjects more frequently exhibited objective signs (joint sounds) of TMD,
      they rarely suffered from pain. In contrast, younger subjects rarely exhibited
      objective TMD signs but more frequently suffered from subjective signs (muscular
      pain on palpation) and facial pain.

PMID- 15975126
TI  - Comparative prospective study on splint therapy of anterior disc displacement
      without reduction.
AB  - A prospective randomized study was carried out to compare the therapeutic success
      of two different types of splint in patients with painful anterior disc
      displacement of the temporomandibular joint. The patients in Group I (n = 20)
      received stabilization splint therapy and the patients in Group II (n = 20) pivot
      splint therapy. Clinical investigation of the craniomandibular system was
      performed before and 1, 2 and 3 months after therapy and this was accompanied by
      subjective evaluation by the patients of their symptoms, using a validated
      questionnaire with visual analogue scales (VAS). There was a significant increase
      in maximum jaw opening and a significant reduction in subjective pain in both
      groups during the course of therapy (Wilcoxon test, P < 0.05). Active jaw opening
      increased by a mean of 8.05 mm in the group of patients treated with a
      stabilization splint (Group I). The comparable figure with pivot splint therapy
      (Group II) was 8.26 mm. The VAS scale value in Group I was reduced by 30.54 units
      and in Group II by 39.36 scale units. However, neither of these differences
      between the groups was statistically significant (Mann-WhitneyU-test, P > 0.05).
      It can be concluded that both types of splint provided effective therapy in
      patients with anterior disc displacement.

PMID- 15975127
TI  - The influence of hot pack therapy on the blood flow in masseter muscles.
AB  - The purpose of this study was to clarify whether hot pack therapy can change the
      blood flow of human masseter muscles. Thirty-two healthy subjects with no history
      of muscle pain in the masticatory system participated and were divided into two
      groups. One group underwent proper hot pack therapy (hot pack group) and the
      other underwent sham hot pack therapy (control group). Continuous and non
      invasive measurements of haemoglobin volumes and oxygen saturation levels (StO2)
      were determined with a near-infrared spectroscope. The blood flow parameters were
      total haemoglobin volume (THb), oxygenated haemoglobin volume (OXHb),
      deoxygenated haemoglobin volume (deOXHb) and oxygen saturation level (StO2). In
      hot pack group, results showed that the THb, OXHb and StO2 after the hot pack
      application were significantly larger than those before the hot pack. In control
      group, the THb, OXHb, deOXHb, StO2 and heart rates showed no significant
      differences between the values before and after the sham hot pack application.
      The THb, OXHb and StO2 after the hot pack application in hot pack group were
      significantly larger than those in control group, while the deOXHb after the hot
      pack was significantly smaller than that in control group. The heart rates showed
      no significant differences between the groups. The results suggest that hot pack
      therapy can increase regional blood flow of human masseter muscles and creates an
      advantageous condition for aerobic energy metabolism in the muscles.

PMID- 15975128
TI  - Breathing type and body position effects on sternocleidomastoid and suprahyoid
      EMG activity.
AB  - The objective of this study was to determine the effects of breathing type and
      body position on sternocleidomastoid and suprahyoid electromyographic (EMG)
      activity. The sample included 18 subjects with upper costal breathing type (study
      group) and 15 subjects with costo-diaphragmatic breathing type (control group).
      All individuals had natural dentition and bilateral molar support. EMG recordings
      at rest and while swallowing saliva were carried out by placing surface
      electrodes on the left sternocleidomastoid and left suprahyoid muscles. EMG
      activity was recorded while standing, seated upright, and in the lateral
      decubitus position. Upper costal breathing type subjects showed a significantly
      higher suprahyoid EMG activity at rest than costo-diaphragmatic subjects in all
      body positions studied (mixed model with unstructured covariance matrix). In the
      lateral decubitus position, both breathing types showed a significantly higher
      sternocleidomastoid EMG activity at rest and while swallowing saliva. The
      suprahyoid muscles demonstrated a significantly higher EMG activity at rest as
      well as in the lateral decubitus position (mixed model with unstructured
      covariance matrix). These results are relevant because sternocleidomastoid and
      suprahyoid muscles play an important role in controlling the head posture and
      mandible dynamics. The neurophysiological mechanisms involved are discussed.

PMID- 15975129
TI  - Oral health-related quality of life of stroke survivors on discharge from
      hospital after rehabilitation.
AB  - The study aimed to investigate oral health-related quality of life (OHR-QoL) of
      stroke survivors on hospital discharge after rehabilitation. It was a cross
      sectional study involving 43 elderly survivors of mild to moderate stroke about
      to be discharged from hospital after rehabilitation and a comparison group of 43
      community-dwelling elderly people. The Medical Outcomes Short Form 36 (SF-36)
      measure, the General Oral Health Assessment Index (GOHAI) and an oral health
      transition scale were administered prior to a dental examination. Median SF-36
      subscale scores were significantly different between groups (P < 0.05). In
      physical function, role-physical, role-emotional and mental health domains,
      stroke survivors had significantly lower scores indicating poorer health. The
      median GOHAI score for the stroke group was 52 and 54 for the comparison group
      with no significant difference between groups although more stroke survivors had
      difficulty speaking compared with the comparison group. About 75% of stroke
      survivors considered their appearance to be worse, half of them felt that speech
      was worse and about a third had difficulty chewing hard food compared with the
      pre-stroke condition (P < 0.05). Most participants were partially dentate with no
      significant difference in DMFT scores or prosthetic status between groups (P >
      0.05). Health-related quality of life in general was significantly poorer after
      stroke although patients were considered physically well enough to be discharged
      from hospital. There was some impairment of OHR-QoL. The nature of the stroke,
      the hospital environment including diet, coping strategies and elderly Chinese
      peoples' perception of health should be taken into account when interpreting
      measures of health status in stroke survivors.

PMID- 15975130
TI  - 3D finite element model and cervical lesion formation in normal occlusion and in
      malocclusion.
AB  - The aim of this study was to develop a three-dimensional (3D) finite element
      model (FEM) of the first maxillary premolar in order to compare the stress
      profiles in the buccal and palatal cervical regions. The 3D geometry of the tooth
      was reconstructed, the solid model was transferred into a finite element program
      where a 3D mesh was created, and the stress distribution analysis was performed.
      Two typical cases have been considered: the tooth under normal occlusion (case I)
      and the tooth under malocclusion (case II). In case I, larger compressive
      stresses were found in the cervical enamel and dentine. Tensile stresses were
      found in the fissure system, adjacent area, and at the vestibular surface of the
      buccal cusp. The peak values for the principal stress ranged from -259 to +2.25
      MPa in the cervical areas. In the case II, larger compressive stresses were found
      in the palato-cervical enamel and dentine. Tensile stresses were found inside the
      enamel in the fissure system, adjacent area, at the vestibular surface of the
      buccal cusp, and in the bucco-cervical enamel. The peak values for the principal
      stress ranged from -501.947 MPa in palatal region to +82.4 MPa in the buccal
      region This study implies a role of occlusal forces in development of non-carious
      lesions. In the case of malocclusion, tensile stresses generated on the cervical
      areas were higher compared with the stresses generated in the case of normal
      occlusion and it is probably capable of producing non-carious cervical lesion.

PMID- 15975131
TI  - In vitro IL-1beta release from gingival fibroblasts in response to pure metals,
      dental alloys and ceramic.
AB  - Little information is available on the immunological basis for side-effects of
      dental materials. The objective of this study is to evaluate effects of pure
      metals, dental alloys and ceramic on cell viability and interleukin-1 beta (IL
      1beta) release in three-dimensional human gingival fibroblast cultures as an
      indicator of their biological performance in gingival tissues. The gingival
      fibroblast cultures were exposed to test specimens fabricated from nickel, iron,
      molybdenum, copper, indium, gold, Ni-Cr-Mo alloy (Remanium CS), Au-Pt-In alloy
      (Pontostar) and a dental ceramic (In-ceram). Cell viability was determined by the
      MTT method 24 and 48 h after exposure. Assays for IL-1beta were carried out by
      ELISA. Statistical analysis was performed applying the non-parametric Mann
      Whitney pairwise test. Dental ceramic and gold did not influence cell viability
      after 24 and 48 h. Cell viability was determined after 24 and 48 h to nickel (79
      77%), iron (92-90%), molybdenum (86-83%), copper (48-36%), indium (90-90%),
      Remanium CS (83-80%), Pontostar (94-91%) compared with control cultures. Dental
      ceramic, Pontostar and gold had no significant influence on IL-1beta secretion.
      The highest amounts of IL-1beta (10-fold) levels were determined in cell cultures
      exposed to copper. Indium, molybdenum and iron induced twofold IL-1beta levels
      compared with untreated control cultures. These results support that some metals
      may alter immune responses and thereby contribute to a variety of dental
      pathological conditions and three-dimensional cell culture models for gingival
      fibroblasts appear to be suitable for in vitro studies.

PMID- 15975132
TI  - Adherence of Candida albicans to glow-discharge modified acrylic denture base
      polymers.
AB  - An important aetiologic factor in the pathogenesis of denture-induced stomatitis,
      is the presence of numerous yeasts, usually Candida albicans, on the fitting
      surfaces of dentures. In the present study, effect of glow-discharge plasma, a
      technique applied to increase surface wettability of acrylic resins, on candidial
      adherence was evaluated. The durability of glow-discharge modification with
      saliva coating was also evaluated. Samples including control and experimental
      groups were prepared by using heat compression mould technique. To create a
      hydrophobicity gradient, experimental groups were exposed to a radiofrequency
      glow discharge in an O2 atmosphere under different discharge powers. To
      characterize the wetting properties, an expression of surface hydrophobicity,
      contact angle measurements were performed by the sessile drop method. The
      organism used was C. albicans (ATTC10321). Acrylic samples were coated with
      unstimulated whole saliva collected from a healthy man. The fungal suspension was
      poured on saliva-inoculated samples and incubated at 37 degrees for 2 h. The
      samples were then fixed with glutaraldehyde and Gram stained. Adhered candidial
      cells were examined by light microscope. Diffuse Reflectance FTIR (DRIFT) and
      scanning electron-microscope examinations were also performed to evaluate the
      surface composition and roughness of the test groups. Glow-discharge plasma was
      found to be an effective means of increasing surface wettability even with
      salivary pellicle. Amounts of candida cells adhered were significantly higher in
      all the plasma treated surfaces than the unmodified control group (P < 0.001). It
      was concluded that improving the surface wettability of acrylic resins by glow
      discharge plasma in O2 atmosphere increased the adherence of the C. albicans.

PMID- 15975133
TI  - Clinical marginal and internal gaps of Procera AllCeram crowns.
AB  - This study evaluated the marginal and internal gaps of Procera AllCeram crowns in
      vivo using silicone materials. Ninety Procera AllCeram crowns were evaluated
      before final cementation. White and black silicone materials were used to record
      the marginal and internal fit; then the crowns were sectioned bucco-lingually and
      mesio-distally to measure the thickness of the silicone layer using a microscope.
      Sixteen reference points were measured on each specimen. Mean marginal gaps among
      anterior, premolar and molar teeth, and mean gaps at the reference points within
      the groups were compared by analysis of variance and Dunnett T3 test. The mean
      values at the margins were the smallest in all tooth groups, whereas those at the
      rounded slope of the chamfer were the largest. There were significant differences
      (P < 0.001) in the mean gaps at the four reference points (margin, rounded slope
      of the chamfer, axial wall and occlusal surface) in each group, except for the
      molar teeth. The mean marginal gaps of the Procera AllCeram crowns were within
      the range of clinical acceptance.

PMID- 15975134
TI  - Microtensile bond strengths to enamel of self-etching and one bottle adhesive
      systems.
AB  - This study compared the enamel bond strengths of self-etching and one bottle
      adhesives, and evaluated microscopically their debonding modes. Evaluated systems
      were: Self-etch--Prompt L-Pop (LP); one bottle, total etch--Single Bond (SB),
      Prime & Bond NT (PB); compomer--Hytac Aplitip (HA), F2000 (F2); resin composite-
      Reference 21 Aplitip (R2), Herculite XRV (XRV), Esthet.X (EX); in the following
      combinations: LP/HA; LP/R2; SB/F2; SB/XRV; PB/EX. Flat surfaces of enamel were
      ground on caries free extracted third molars. An adhesive resin was applied to
      this surface and a restorative material built on it. The teeth were sectioned
      longitudinally into 1 mm thick specimens and trimmed to a 1 mm2 area at the
      enamel/adhesive interface. For each material combination, 10 specimens were
      tested. Microtensile bond strengths were determined at 0.5 mm min(-1). Fractured
      specimens were examined using confocal and scanning electron microscopy to
      determine failure modes. Bond strength data was analysed using Kaplan-Meier
      survival analysis, a log-rank test and a Bonferroni multiple comparison. Failure
      mode data was analysed with a chi2 test. The interface of additional fluorescent
      labelled specimens was examined by laser scanning confocal microscopy. The bond
      strength data showed significant differences: LP/R2 > LP/HA, SB/F2 and PB/EX;
      SB/F2 < LP/HA, SB/XRV and PB/EX. Both compomers principally exhibited cohesive
      failure. Resin composite materials showed more complex failure modes.
      Fluorescence images demonstrated interfacial characteristics consistent with the
      failure modes observed. SIGNIFICANCE: bond strength was not influenced by the use
      of self-etch or one bottle adhesives.

PMID- 15975135
TI  - Rehabilitation of a bilateral maxillectomy patient with a free fibula
      osteocutaneous flap.
AB  - Rehabilitation of patients who have undergone bilateral maxillectomy is difficult
      because of extensive loss of bone and soft tissue. In this clinical report,
      prosthodontic rehabilitation of oral function in a bilateral maxillecitomy
      patient combined with a new fibular osteocutaneous flap, which was designed to
      have two oronasal slits for the retention of an obturator prosthesis, was
      described. A 58-year-old man with a maxillary alveolar carcinoma underwent
      bilateral maxillectomy. The defect was reconstructed using a vascularized fibular
      bone wrapped circumferentially with a peroneal flap, which was fixed with
      miniplates between the right malar prominence and cut edge of the left zygoma
      remaining two slits anterior and posterior to the graft. Two and half weeks after
      the surgery, a delayed surgical obturator was delivered and an obturator
      prosthesis was delivered 6 weeks after the surgery. This obturator prosthesis
      could be extended into the slits to engage the tissue undercuts, and was stable
      during use. Mastication, deglutition, articulation and the mid-facial profile of
      the patient were rehabilitated. After installation of the obturator prosthesis,
      relining of the prosthesis base was carried out alongside the healing process of
      the graft, and adjustment of occlusions and high-pressure spots was carried out.
      No clinical disorders were observed either in the grafted tissue or the obturator
      prosthesis with a 3-year prognosis. Newly designing a fibular osteocutaneous flap
      combined with tissue-borne obturator prosthesis is one successful approach to the
      restoration of oral function, and increases the patient's quality of life after
      bilateral maxillectomy.

PMID- 15975136
TI  - The factor V Glu1608Lys mutation is recurrent in familial thrombophilia.
AB  - BACKGROUND: Co-inheritance of heterozygous factor V deficiency with FV Leiden
      enhances the activated protein C resistance (APCR) associated with this mutation,
      resulting in pseudo-homozygous APCR. The role of FV deficiency in modulating
      thrombotic risk in this rare condition is poorly understood. METHODS AND RESULTS:
      We have identified in thrombophilic patients with FV deficiency a novel FV gene
      mutation (c. 4996G>A), predicting the Glu1608Lys substitution in the A3 domain.
      The heterozygous mutation was detected in three unrelated patients, two carriers
      of the FV Leiden mutation, and one of the FVHR2 haplotype. The Glu1608Lys change
      was also present in two subjects with mild FV deficiency, and absent in 200
      controls. The FV1608Lys carriers showed reduced mean FV activity (42% +/- 12%)
      and antigen (53% +/- 18%) levels and, in Western blot analysis, reduced amounts
      of intact platelet FV. The restriction fragment length polymorphism (RFLP) study
      identified two haplotypes underlying the mutation, which suggests that it is
      recurrent. In heterozygous subjects the amount of FV1608Lys mRNA in white blood
      cells was similar to that produced by the counterpart alleles (FVWt or FVHR2).
      Recombinant FV1608Lys (rFV1608Lys), detected by Western blot in the conditioned
      medium, was indistinguishable from rFVWt and FV antigen and activity were found
      to be respectively 44% +/- 20% and 13% +/- 4% of rFVWt. CONCLUSIONS: Our data
      indicate that FVGlu1608Lys predicts a CRM (plasma)/CRMred (cell culture) FV
      deficiency, and may contribute to thrombophilia in carriers of FV Leiden and
      FVHR2 haplotype via a pseudo-homozygosity mechanism. Our findings help to define
      the molecular bases of FV deficiency and thrombophilia.

PMID- 15975137
TI  - The role of thrombin in gliomas.
AB  - BACKGROUND: In a previous study we found that intracerebral infusion of
      argatroban, a specific thrombin inhibitor, reduces brain edema and neurologic
      deficits in a C6 glioma model. OBJECTIVES: To examine the role of thrombin in
      gliomas and whether systemic argatroban administration can reduce glioma mass and
      neurologic deficits and extend survival time in C6 and F98 gliomas. METHODS: The
      presence of thrombin in human glioblastoma samples and rat C6 glioma cells (in
      vitro and in vivo) was assessed using immunohistochemistry. The effect of
      thrombin on C6 cell proliferation in vitro was assessed using a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The role of
      thrombin in vivo was assessed in rat C6 and F98 glioma cell models using
      argatroban, a thrombin inhibitor. The effects of argatroban on tumor mass,
      neurologic deficits and survival time were investigated. RESULTS: Thrombin
      immunoreactivity was found in cultured rat C6 glioma cells and human
      glioblastomas. Thrombin induced C6 cell proliferation in vitro. In C6 glioma,
      argatroban reduced glioma mass (P < 0.05) and neurologic deficits (P < 0.05) at
      day 9. In F98 glioma, argatroban prolonged survival time (P < 0.05). CONCLUSION:
      These results suggest that thrombin plays an important role in glioma growth.
      Thrombin may be a new therapeutic target for gliomas.

PMID- 15975138
TI  - VHL: oxygen sensing and vasculogenesis.

PMID- 15975139
TI  - Deep vein thrombosis associated with central venous catheters - a review.

PMID- 15975140
TI  - A randomised controlled trial to explore attitudes to routine scale and polish
      and compare manual versus ultrasonic scaling in the general dental service in
      Scotland [ISRCTN99609795].
AB  - BACKGROUND: To investigate, within general dental practice, patients' and
      vocational dental practitioners' (VDP) attitudes towards the benefits and costs
      of a simple scale and polish and to compare the experience of using manual versus
      ultrasonic instruments to scale teeth. METHODS: 28 VDPs and 420 patients
      participated. Patients were randomly allocated to either group. Patients' and
      VDPs' attitudes towards, and experience of, the scale and polish were elicited by
      means of self-administered questionnaires. RESULTS: The majority of patients
      (99%) believed a scale and polish was beneficial. VDPs considered ultrasonic
      treatment to be appropriate on significantly more occasions than they did for
      manual scale and polish (P < 0.001). Patient discomfort: with ultrasonic scaling
      69.2% felt 'a little uncomfortable' or worse compared with 60% of those
      undergoing manual treatment (P = 0.072). VDPs considered treatment charges were
      appropriate for 77% of patients. CONCLUSION: Routine scaling and polishing is
      considered beneficial by both patients and vocational trainees. The majority of
      patients, regardless of treatment method, experience some degree of discomfort
      when undergoing a scale and polish. VDPs showed a preference for the ultrasonic
      treatment method.

PMID- 15975141
TI  - Sequence signature analysis of chromosome identity in three Drosophila species.
AB  - BACKGROUND: All eukaryotic organisms need to distinguish each of their
      chromosomes. A few protein complexes have been described that recognise entire,
      specific chromosomes, for instance dosage compensation complexes and the recently
      discovered autosome-specific Painting of Fourth (POF) protein in Drosophila.
      However, no sequences have been found that are chromosome-specific and
      distributed over the entire length of the respective chromosome. Here, we present
      a new, unbiased, exhaustive computational method that was used to probe three
      Drosophila genomes for chromosome-specific sequences. RESULTS: By combining
      genome annotations and cytological data with multivariate statistics related to
      three Drosophila genomes we found sequence signatures that distinguish Muller's F
      elements (chromosome 4 in D. melanogaster) from all other chromosomes in
      Drosophila that are not attributable to differences in nucleotide composition,
      simple sequence repeats or repeated elements. Based on these signatures we
      identified complex motifs that are strongly overrepresented in the F-elements and
      found indications that the D. melanogaster motif may be involved in POF-binding
      to the F-element. In addition, the X-chromosomes of D. melanogaster and D. yakuba
      can be distinguished from the other chromosomes, albeit to a lesser extent.
      Surprisingly, the conservation of the F-element sequence signatures extends not
      only between species separated by approximately 55 Myr, but also linearly along
      the sequenced part of the F-elements. CONCLUSION: Our results suggest that
      chromosome-distinguishing features are not exclusive to the sex chromosomes, but
      are also present on at least one autosome (the F-element) in Drosophila.

PMID- 15975142
TI  - Evaluation of the HOOF-Print assay for typing Brucella abortus strains isolated
      from cattle in the United States: results with four performance criteria.
AB  - BACKGROUND: A fundamental question that arises during epidemiological
      investigations of bacterial disease outbreaks is whether the outbreak strain is
      genetically related to a proposed index strain. Highly discriminating genetic
      markers for characterizing bacterial strains can help in clarifying the genetic
      relationships among strains. Under the auspices of the European Society of
      Clinical Microbiology and Infectious Diseases, the European Study Group for
      Epidemiological Markers (ESGEM) established guidelines for evaluating the
      performance of typing systems based of a number of criteria. Recently, HOOF-Print
      genotype analysis, a new method for typing Brucella abortus strains based on
      hypervariability at eight tandem repeat loci, was described. This paper evaluates
      the HOOF-Print assay by four of the criteria set out by the ESGEM: typeability,
      reproducibility, power of discrimination, and concordance with other typing
      methods. RESULTS: The HOOF-Print Assay was evaluated with a test population
      composed of 97 unrelated field isolates and 6 common laboratory strains of B.
      abortus. Both typeability and reproducibility of the assay were excellent. Allele
      diversity and frequency varied widely among the eight loci, ranging from 1 to 13
      alleles. The power of discrimination, measured by the Hunter-Gaston
      discrimination index (HGDI), varied by locus ranging from 0 to 0.89, where a
      maximal value of 1.0 indicates discrimination of all strains. The HGDI values
      calculated for subgroups sorted by biovar were similar to the values determined
      for the whole population. None of the individual loci achieved the recommended
      HGDI threshold of 0.95, but the HGDI of the composite profiles was 0.99 (93
      unique genotypes from 97 field strains evaluated), well above the recommended
      threshold. By comparison, the HGDI value for biovar typing was 0.61 in a test
      population biased with disproportionate numbers of the less common biovars.
      Cluster analysis based on HOOF-Print genotypes assembled the strains into
      hierarchical groups with no apparent association with the time or location of
      strain isolation. Likewise, these hierarchical groups were not homogeneous with
      regard to biotype. In one extreme case, two field isolates with identical
      fingerprints were identified as different biovars by conventional methods.
      CONCLUSION: The main purpose of this study was to assess the ability of HOOF
      Print genotyping to discriminate unrelated field strains of B. abortus, and
      whether the assay met established requirements for bacterial strain typing
      methods. The discriminatory power of the assay was remarkable, considering the
      genetic homogeneity found among species within the genus. The assay met or
      exceeded all of the recommended levels for the performance criteria of
      typeability, reproducibility, and power of discrimination, however some
      inconsistencies with conventional biovar typing were observed. Nevertheless, the
      results indicate that with cautious interpretation, multilocus genotyping of
      polymorphic tandem repeats by HOOF-Print analysis could be a valuable complement
      to routine epidemiological investigations into localized B. abortus outbreaks.

PMID- 15975143
TI  - Age-related human small intestine methylation: evidence for stem cell niches.
AB  - BACKGROUND: The small intestine is constructed of many crypts and villi, and
      mouse studies suggest that each crypt contains multiple stem cells. Very little
      is known about human small intestines because mouse fate mapping strategies are
      impractical in humans. However, it is theoretically possible that stem cell
      histories are inherently written within their genomes. Genomes appear to record
      histories (as exemplified by use of molecular clocks), and therefore it may be
      possible to reconstruct somatic cell dynamics from somatic cell errors. Recent
      human colon studies suggest that random somatic epigenetic errors record stem
      cell histories (ancestry and total numbers of divisions). Potentially age-related
      methylation also occurs in human small intestines, which would allow
      characterization of their stem cells and comparisons with the colon. METHODS:
      Methylation patterns in individual crypts from 13 small intestines (17 to 78
      years old) were measured by bisulfite sequencing. The methylation patterns were
      analyzed by a quantitative model to distinguish between immortal or niche stem
      cell lineages. RESULTS: Age-related methylation was observed in the human small
      intestines. Crypt methylation patterns were more consistent with stem cell niches
      than immortal stem cell lineages. Human large and small intestine crypt niches
      appeared to have similar stem cell dynamics, but relatively less methylation
      accumulated with age in the small intestines. There were no apparent stem cell
      differences between the duodenum and ileum, and stem cell survival did not appear
      to decline with aging. CONCLUSION: Crypt niches containing multiple stem cells
      appear to maintain human small intestines. Crypt niches appear similar in the
      colon and small intestine, and the small intestinal stem cell mitotic rate is the
      same as or perhaps slower than that of the colon. Although further studies are
      needed, age-related methylation appears to record somatic cell histories, and a
      somatic epigenetic molecular clock strategy may potentially be applied to other
      human tissues to reconstruct otherwise occult stem cell histories.

PMID- 15975144
TI  - Huge parathyroid carcinoma: clinical considerations and literature review.
AB  - BACKGROUND: Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5
      to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative
      treatment. CASE PRESENTATION: We report the case of a 66-year-old man referred
      for a large suspicious substernal goitre associated with severe hypercalcemia due
      to hyperparathyroidism. After normalization of serum calcium levels, patient
      underwent surgery. The voluminous cervicomediastinal firm mass could not be
      removed through the cervical incision; therefore a cervicothoracic approach was
      employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A
      review of the literature was also undertaken to summarize the current treatment
      approaches for this rare malignancy. CONCLUSION: Parathyroid cancer is usually
      not recognized either preoperatively or intra-operatively. En bloc resection of
      the tumour with the adjacent tissue is the treatment of choice and it is very
      important to avoid the rupture of the capsule during operation. Neither tumour
      size, nor the lymph node status appears to play a role in prognosis. The
      management of parathyroid carcinoma is a challenge even for experienced surgeons.

PMID- 15975145
TI  - Benzodiazepine prescribing behaviour and attitudes: a survey among general
      practitioners practicing in northern Thailand.
AB  - BACKGROUND: Over-prescribing of benzodiazepines appears common in many countries,
      a better understanding of prescribing practices and attitudes may help develop
      strategies to reduce prescribing. This study aimed to evaluate benzodiazepine
      prescribing behaviour and attitudes in general practitioners practising in Chiang
      Mai and Lampoon, Thailand. METHODS: Questionnaire survey of general practitioners
      in community hospitals, to estimate: i) use of benzodiazepines for
      anxiety/insomnia, panic disorder, depression, essential hypertension, and
      uncomplicated low back pain and ii) views on the optimal duration of
      benzodiazepine use. RESULTS: Fifty-five of 100 general practitioners returned the
      completed questionnaires. They reported use of benzodiazepines for
      anxiety/insomnia (n = 51, 93%), panic disorder (n = 43, 78%), depression (n = 26,
      43%), essential hypertension (n = 15, 27 %) and uncomplicated low back pain (n =
      10, 18%). Twenty-eight general practitioners would prescribe benzodiazepines for
      non-psychiatric conditions, 17 for use as muscle relaxants. Seventy-five per
      cent, 62% and 29% of the general practitioners agreed or totally agreed with the
      use of benzodiazepines for insomnia, anxiety and depression, respectively.
      Practitioners agreed that prescribing should be less than one week (80%); or from
      1 week to 1 month (47%); or 1 to 4 months (16%); or 4 to 6 months (5%) or more
      than 6 months (2%). Twenty-five general practitioners (45%) accepted that they
      used benzodiazepines excessively in the past year. CONCLUSION: A considerable
      proportion of general practitioners in Chiang Mai and Lampoon, Thailand
      inappropriately use benzodiazepines for physical illnesses, especially essential
      hypertension and uncomplicated low back pain. However, almost half of them
      thought that they overused benzodiazepines. General practitioner's lack of time,
      knowledge and skills should be taken into account in improving prescribing
      behaviour and attitudes.

PMID- 15975146
TI  - Clustered local transmission and asymptomatic Plasmodium falciparum and
      Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian
      Amazon community.
AB  - BACKGROUND: There is a low incidence of malaria in Iquitos, Peru, suburbs
      detected by passive case-detection. This low incidence might be attributable to
      infections clustered in some households/regions and/or undetected asymptomatic
      infections. METHODS: Passive case-detection (PCD) during the malaria season
      (February-July) and an active case-detection (ACD) community-wide survey (March)
      surveyed 1,907 persons. Each month, April-July, 100-metre at-risk zones were
      defined by location of Plasmodium falciparum infections in the previous month.
      Longitudinal ACD and PCD (ACP+PCD) occurred within at-risk zones, where 137
      houses (573 persons) were randomly selected as sentinels, each with one month of
      weekly active sampling. Entomological captures were conducted in the sentinel
      houses. RESULTS: The PCD incidence was 0.03 P. falciparum and 0.22 Plasmodium
      vivax infections/person/malaria-season. However, the ACD+PCD prevalence was 0.13
      and 0.39, respectively. One explanation for this 4.33 and 1.77-fold increase,
      respectively, was infection clustering within at-risk zones and contiguous
      households. Clustering makes PCD, generalized to the entire population,
      artificially low. Another attributable-factor was that only 41% and 24% of the P.
      falciparum and P. vivax infections were associated with fever and 80% of the
      asymptomatic infections had low-density or absent parasitaemias the following
      week. After accounting for asymptomatic infections, a 2.6-fold increase in
      ACD+PCD versus PCD was attributable to clustered transmission in at-risk zones.
      CONCLUSION: Even in low transmission, there are frequent highly-clustered
      asymptomatic infections, making PCD an inadequate measure of incidence. These
      findings support a strategy of concentrating ACD and insecticide campaigns in
      houses adjacent to houses were malaria was detected one month prior.

PMID- 15975148
TI  - Hypertensive crisis associated with high dose soy isoflavone supplementation in a
      post-menopausal woman: a case report [ISRCTN98074661].
AB  - BACKGROUND: Isoflavones are gaining popularity as alternatives to hormone
      replacement therapy. However, few guidelines exist to inform the public as to an
      appropriate dose. This case involves a postmenopausal woman who experienced a
      hypertensive crisis while consuming a high-dose isoflavone supplement as part of
      a research protocol. CASE PRESENTATION: The participant was part of a placebo
      controlled crossover trial to investigate the potential synergism of the
      antioxidant activity of soy isoflavones and vitamin C. Upon entry into the study,
      this healthy, well-nourished, normotensive postmenopausal woman (51 years old),
      consumed the first of four randomly assigned treatments (500 mg vitamin C plus 5
      mg/kg body weight soy isoflavones). During this treatment, the participant's
      systolic blood pressure spiked to a recorded 226/117 mmHg, necessitating medical
      intervention and discontinuation of study participation. Two plausible mechanisms
      for this hypertensive crisis are discussed. CONCLUSION: Due to the availability
      and increasing popularity of soy supplements, practitioners should be aware of
      the potential side effects associated with their use. Practitioners counseling
      clients who are consuming soy isoflavone supplements should advise them that
      elevated blood pressure may be a potential side-effect to consider and monitor.

PMID- 15975147
TI  - The influence of long chain polyunsaturate supplementation on docosahexaenoic
      acid and arachidonic acid in baboon neonate central nervous system.
AB  - BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major
      components of the cerebral cortex and visual system, where they play a critical
      role in neural development. We quantitatively mapped fatty acids in 26 regions of
      the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA
      and ARA supplementation and prematurity on CNS DHA and ARA concentrations.
      METHODS: Baboons were randomized into a breastfed (B) and four formula-fed
      groups: term, no DHA/ARA (T-); term, DHA/ARA supplemented (T+); preterm, no
      DHA/ARA (P-); preterm and DHA/ARA supplemented (P+). At four weeks adjusted age,
      brains were dissected and total fatty acids analyzed by gas chromatography and
      mass spectrometry. RESULTS: DHA and ARA are rich in many more structures than
      previously reported. They are most concentrated in structures local to the brain
      stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus
      and midbrain, and comparatively lower in white matter. Dietary supplementation
      increased DHA in all structures but had little influence on ARA concentrations.
      Supplementation restored DHA concentrations to levels of breastfed neonates in
      all regions except the cerebral cortex and cerebellum. Prematurity per se did not
      exert a strong influence on DHA or ARA concentrations. CONCLUSION: 1) DHA and ARA
      are found in high concentration throughout the primate CNS, particularly in gray
      matter such as basal ganglia; 2) DHA concentrations drop across most CNS
      structures in neonates consuming formulas with no DHA, but ARA levels are
      relatively immune to ARA in the diet; 3) supplementation of infant formula is
      effective at restoring DHA concentration in structures other than the cerebral
      cortex. These results will be useful as a guide to future investigations of CNS
      function in the absence of dietary DHA and ARA.

PMID- 15975149
TI  - CD14 C-159T and early infection with Pseudomonas aeruginosa in children with
      cystic fibrosis.
AB  - Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis
      in patients with cystic fibrosis. We investigated whether polymorphisms in CD14,
      the lipopolysaccharide receptor, increase the risk of early infection. Forty-five
      children with cystic fibrosis were investigated with annual bronchoalveolar
      lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly
      lower in children from whom P.aeruginosa was subsequently isolated (492.75
      microg/ml vs. 1339.43 microg/ml, p = 0.018). Those with the CD14 -159CC genotype
      had a significantly increased risk of early infection with P.aeruginosa
      suggesting that CD14 C-159T plays a role in determining the risk of early
      infection with P.aeruginosa.

PMID- 15975150
TI  - Pruritus in hemodialysis patients.
AB  - BACKGROUND: Pruritus is one of the most bothersome symptoms in patients on
      maintenance hemodialysis (HD), however little progress is seen in our
      understanding of its pathogenesis. The aim of this study was to evaluate the
      frequency of pruritus in HD patients in Tehran, Iran, and to correlate its
      presence and intensity with relevant clinical and laboratory parameters. METHODS:
      One hundred sixty-seven patients on maintenance HD at three out-patient HD units
      were enrolled in the study. Itch intensity was scored as mild, moderate and
      severe. Some relevant clinical and laboratory parameters (age, sex, xerosis,
      presence of neuropathy, duration of dialysis, history of atopy and laboratory
      findings including hematocrit, creatinine, urea, calcium, phosphorus, parathyroid
      hormone [PTH] and alkaline phosphatase) were evaluated. RESULTS: Pruritus was
      found in 41.9% of patients. The intensity of itching was mild, moderate and
      severe, in 51.4%, 11.4% and 37.7% of patients, respectively. In 22 patients
      (31.4%) pruritus intensified during and after dialysis. There was no significant
      difference in the serum levels of creatinine, blood urea nitrogen, calcium,
      phosphorus, alkaline phosphatase, PTH and hematocrit between patients with and
      without pruritus. Age, sex, xerosis, underlying renal disease, history of atopy
      and duration of haemodialysis were not significantly different between the two
      groups. However, neuropathy was significantly more common in the pruritic group
      (63.8% versus 42.1%) (pv = 0.006). CONCLUSION: Clinical neuropathy was the only
      significant finding in the pruritic group in our study. This finding justifies
      further research on nerve function and neurotransmitters in hemodialysis patients
      and the introduction of new drugs targeting neuropathy.

PMID- 15975153
TI  - VI Madrid Breast Cancer Conference: Changes in the treatment of breast cancer.
      Madrid, Spain. 1 June - 3 June 2005. Abstracts.

PMID- 15975151
TI  - Bone mineral density, body mass index and cigarette smoking among Iranian women:
      implications for prevention.
AB  - BACKGROUND: While risk factors of osteoporosis in Western populations have been
      extensively documented, such a profile has not been well studied in Caucasians of
      non-European origin. This study was designed to estimate the modifiable
      distribution and determinants of bone mineral density (BMD) among Iranian women
      in Australia. METHODS: Ninety women aged 35 years and older completed a
      questionnaire on socio-demographic and lifestyle factors. BMD was measured at the
      lumbar spine (LS) and femoral neck (FN) using DXA (GE Lunar, WI, USA), and was
      expressed in g/cm2 as well as T-score. RESULTS: In multiple regression analysis,
      advancing age, lower body mass index (BMI), and smoking were independently
      associated with LS and FN BMD, with the 3 factors collectively accounting for 30%
      and 38% variance of LS and FN BMD, respectively. LS and FN BMD in smokers was 8%
      lower than that in non-smokers. Further analysis of interaction between BMI and
      smoking revealed that the effect of smoking was only observed in the obese group
      (p = 0.029 for LSBMD and p = 0.007 for FNBMD), but not in the overweight and
      normal groups. Using T-scores from two bone sites the prevalence of osteoporosis
      (T-scores <or= -2.5) was 3.8% and 26.3% in pre-and post-menopausal women,
      respectively. Among current smokers, the prevalence was higher (31.3%) than that
      among ex-smokers (28.6%) and non-smokers (7.5%). CONCLUSION: These data, for the
      first time, indicate that apart from advancing age and lower body mass index,
      cigarette smoking is an important modifiable determinant of bone mineral density
      in these Caucasians of non-European origin.

PMID- 15975154
TI  - New approaches to the study of dietary patterns.

PMID- 15975155
TI  - The effects of drinks made from simple sugars on blood pressure in healthy older
      people.
AB  - The objective of the research was to determine the blood pressure (BP) lowering
      effects in older people of 50 g carbohydrate drinks with varying carbohydrate
      content using a randomised, cross-over study with ten (six females) healthy older
      subjects (mean age 72.20 (sem 1.50) years). BP, heart rate and glucometer-derived
      blood glucose levels were determined at baseline and following the ingestion of
      equal volumes (300 ml) of water and carbohydrate drinks with varying nutrient
      content (glucose, sucrose and fructose). A significant decline in BP over the
      first 60 min was seen following glucose (systolic BP (SBP) P<0.01, diastolic BP
      (DBP) P<0.01, mean arterial BP (MAP) P=0.03) and sucrose (SBP P<0.01, DBP P<0.01,
      MAP P<0.01) ingestion, although the decrease occurred earlier after glucose than
      sucrose ingestion (SBP 7.33 (sem 2.19) v. 21.00 (sem 4.30) min (P=0.03) and MAP
      11.22 (sem 3.10) v. 17.00 (sem 3.78) min (P=0.03)). BP increased after water
      ingestion (SBP P=0.04, DBP P=0.18, MAP P=0.02) but did not change after fructose
      ingestion (SBP P=0.36, DBP P=0.81, MAP P=0.34). Post hoc analyses revealed that
      the BP (SBP, DBP and MAP) decrease following glucose and sucrose ingestion were
      similar but significantly greater than following fructose or water ingestion.
      Sucrose, which is used widely (table sugar), reduces BP as much as glucose. In
      contrast to this, fructose ingestion causes no change in BP. Further studies are
      required to determine if the substitution of glucose or sucrose with fructose may
      be beneficial in the medical management of older people with severe symptomatic
      postprandial hypotension.

PMID- 15975157
TI  - The influence of erythrocyte folate and serum vitamin B12 status on birth weight.
AB  - The extent to which maternal folate and vitamin B12 modulate infant birth weight
      is unclear. The present study investigated mothers in early gestation (mean 11.5
      (sd 5.8) weeks) and neonates, at delivery. Erythrocyte (RBC) folate (mothers: n
      683; neonates: n 614) and vitamin B12 (mothers: n 534; neonates: n 614) were
      measured. Data on smoking habits were available for 44 % of pregnancies (n 443).
      The relationship between vitamin levels and birth weight standardized for gender
      and gestational age was investigated, using linear regression and adjusting for
      possible confounding variables (maternal age, parity). Results are presented as
      standardized regression coefficients (b). Increasing maternal age was associated
      with elevated RBC folate (b 0.11 (95 % CI 0.08, 0.15), P<0.001; n 674) and
      smoking was associated with a decrease in maternal RBC folate (b -1.38 (95 % CI 
      1.92, -0.86), P=0.001; n 319). Neonatal RBC folate was predicted by maternal RBC
      folate (b 0.08 (95 % CI 0.04, 0.11), P=0.001; n 315) and maternal vitamin B12 (b
      0.08 (95 % CI 0.01, 0.16), P=0.02; n 252). Smoking influenced maternal vitamin
      B12 status (b -0.88 (95 % CI -1.49, -0.27), P=0.005; n 231). Using univariate
      regression, smoking significantly influenced infant birth weight (b -2.15 (95 %
      CI -3.24, -1.04), P<0.001; n 437). However, the effect of smoking on birth weight
      was statistically non-significant when considered in a multivariate regression
      model, leaving maternal RBC folate as the only significant predictor of birth
      weight (b 0.25 (95 % CI 0.08, 0.42), P=0.005; n 145). These findings suggest that
      maternal folate status is an important determinant of infant birth weight. The
      combined effects of smoking and reduced RBC status on birth weight require
      further investigation.

PMID- 15975156
TI  - Differential inhibition of oxidized LDL-induced apoptosis in human endothelial
      cells treated with different flavonoids.
AB  - High plasma level of cholesterol is a well-known risk factor for atherosclerotic
      diseases. Oxidized LDL induces cellular and nuclear damage that leads to
      apoptotic cell death. We tested the hypothesis that flavonoids may function as
      antioxidants with regard to LDL incubated with 5 microm-Cu(2+) alone or in
      combination with human umbilical vein endothelial cells (HUVEC). Cytotoxicity and
      formation of thiobarbituric acid-reactive substances induced by Cu(2+)-oxidized
      LDL were examined in the presence of various subtypes of flavonoid. Flavanols,
      flavonols and flavanones at a non-toxic dose of 50 microm markedly inhibited LDL
      oxidation by inhibiting the formation of peroxidative products. In contrast, the
      flavones luteolin and apigenin had no such effect, with >30 % of cells killed
      after exposure to 0.1 mg LDL/ml. Protective flavonoids, especially (-)
      epigallocatechin gallate, quercetin, rutin and hesperetin, inhibited HUVEC
      nuclear condensation and fragmentation induced by Cu(2+)-oxidized LDL. In
      addition, immunochemical staining and Western blot analysis revealed that anti
      apoptotic Bcl-2 expression was enhanced following treatment with these protective
      flavonoids. However, Bax expression and caspase-3 cleavage stimulated by 18 h
      incubation with oxidized LDL were reduced following treatment with these
      protective flavonoids. The down-regulation of Bcl-2 and up-regulation of caspase
      3 activation were reversed by the cytoprotective flavonoids, (-)-epigallocatechin
      gallate, quercetin and hesperetin, at >/=10 microm. These results suggest that
      flavonoids may differentially prevent Cu(2+)-oxidized LDL-induced apoptosis and
      promote cell survival as potent antioxidants. Survival potentials of certain
      flavonoids against cytotoxic oxidized LDL appeared to stem from their disparate
      chemical structure. Furthermore, dietary flavonoids may have therapeutic
      potential for protecting the endothelium from oxidative stress and oxidized LDL
      triggered atherogenesis.

PMID- 15975158
TI  - Maternal dietary 22 : 6n-3 is more effective than 18 : 3n-3 in increasing the 22
      : 6n-3 content in phospholipids of glial cells from neonatal rat brain.
AB  - One of the debates in infant nutrition concerns whether dietary 18 : 3n-3
      (linolenic acid) can provide for the accretion of 22 : 6n-3 (docosahexaenoic
      acid, DHA) in neonatal tissues. The objective of the present study was to
      determine whether low or high 18 : 3n-3 v. preformed 22 : 6n-3 in the maternal
      diet enabled a similar 22 : 6n-3 content in the phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine
      (PS) of glial cells from whole brain (cerebrum and cerebellum) of 2-week-old rat
      pups. At parturition, the dams were fed semi-purified diets containing either
      increasing amounts of 18 : 3n-3 (18 : 2n-6 to 18 : 3n-3 fatty acid ratio of 7.8 :
      1, 4.4 : 1 or 1 : 1), preformed DHA, or preformed 20 : 4n-6 (arachidonic
      acid)+DHA. During the first 2 weeks of life, the rat pups from the respective
      dams received only their dam's milk. The fatty acid composition of the pups'
      stomach contents (dam's milk) and phospholipids from glial cells were quantified.
      The 20 : 4n-6 and 22 : 6n-3 content in the stomach from rat pups at 2 weeks of
      age reflected the fatty acid composition of the dam's diet. The 20 : 4n-6 content
      of PE and PS in the glial cells was unaffected by maternal diet treatments.
      Preformed 22 : 6n-3 in the maternal diet increased the 22 : 6n-3 content of glial
      cell PE and PS compared with maternal diets providing an 18 : 2n-6 to 18 : 3 n-3
      fatty acid ratio of 7.8 : 1, 4.4 : 1 or 1 : 1 (P<0.0001). There was no
      significant difference in the 20 : 4n-6 and 22 : 6n-3 content of glial cell PC
      and PI among maternal diet treatments. It was concluded that maternal dietary 22
      : 6n-3 is more effective than low or high levels of maternal dietary 18 : 3n-3 at
      increasing the 22 : 6n-3 content in PE and PS of glial cells from the whole brain
      of rat pups at 2 weeks of age. The findings from the present study have important
      implications for human infants fed infant formulas that are devoid of 22 : 6n-3.

PMID- 15975159
TI  - Long-term sucrose-drinking causes increased body weight and glucose intolerance
      in normal male rats.
AB  - The current epidemic of diabetes likely reflects marked changes in environmental
      factors, although genetic susceptibility plays a powerful role in the occurrence
      of diabetes in certain populations. We investigated whether long-term sucrose
      drinking causes hyperglycaemia in male Wistar-Imamichi littermates (n 32), which
      are not genetically susceptible to diabetes or obesity. Each litter was divided
      equivalently into two groups, the sucrose group and the control group. The
      sucrose group received 300 g/l sucrose water and the control group received
      regular water until 42 weeks of age. Rats were weighed every 1 or 2 weeks. Oral
      glucose tolerance tests were performed at 28 and 36 weeks of age. Plasma glucose
      and insulin concentrations were measured. Body weights were significantly greater
      in the sucrose group than in the control group in 18-week-old rats (P<0.05), and
      the difference between the two groups reached 163 g by the end of the study
      (P<0.01). The 120 min post-load plasma glucose concentration in the sucrose group
      was 11.4 (SD 2.8) mmol/l in 28-week-old rats and 12.7 (SD 2.2) mmol/l in 36-week
      old rats, while that of the control group remained approximately 7.3-7.7 mmol/l.
      In the sucrose group, the plasma insulin peak occurred 30 min post-load at 28
      weeks of age; but the peak disappeared and hyperinsulinaemia was prolonged at 36
      weeks of age. In conclusion, long-term sucrose-drinking causes increased body
      weight and glucose intolerance in normal male rats.

PMID- 15975160
TI  - Total antioxidant capacity of the diet is inversely and independently related to
      plasma concentration of high-sensitivity C-reactive protein in adult Italian
      subjects.
AB  - Inflammation, a risk factor for cardiovascular disease, is associated with low
      plasma levels of antioxidant vitamins. In addition to vitamins, other
      antioxidants modulate the synthesis of inflammatory markers in vitro and
      contribute to the total antioxidant capacity (TAC) of a diet. However, the
      relationship between dietary TAC and markers of inflammation has never been
      evaluated in vivo. We investigated the relationship between dietary TAC and
      markers of systemic (high-sensitivity C-reactive protein (hs-CRP), leucocytes)
      and vascular (soluble intercellular cell adhesion molecule-1) inflammation in 243
      non-diabetic subjects. General Linear Model (GLM) analysis showed a significant
      (P=0.005) inverse relationship between hs-CRP and quartiles of energy-adjusted
      dietary TAC, even when recognized modulating factors of inflammation, namely
      alcohol, fibre, vitamin C, alpha-tocopherol, beta-carotene, BMI, waist
      circumference, HDL-cholesterol, hypertension, insulin sensitivity and plasma beta
      carotene, were included in the model as covariates (P=0.004). The relationship
      was stronger for subjects with hypertension (P=0.013 v. P=0.109 for normotensive
      individuals). Among dietary factors, TAC was significantly higher (5.3 (sd 3.0)
      v. 4.9 (sd 2.7) mmol Trolox/d; P=0.026) in subjects with low plasma hs-CRP
      (range: 0.0-4.1 mg/l) than in subjects with high plasma hs-CRP (range: 4.2-27.8
      mg/l). We conclude that dietary TAC is inversely and independently correlated
      with plasma concentrations of hs-CRP and this could be one of the mechanisms
      explaining the protective effects against CVD of antioxidant-rich foods such as
      fruits, whole cereals and red wine. This could be of particular significance for
      subjects with high blood pressure.

PMID- 15975161
TI  - The 'anomalous' absorption of labelled and unlabelled vitamin C in man.
AB  - Previous studies of vitamin C absorption in man using stable isotope probes have
      given results which cannot easily be reconciled with those obtained using non
      isotope measurement. In order to investigate some of the apparent paradoxes we
      have conducted a study using two consecutive doses of vitamin C, one labelled and
      one unlabelled, given 90 min apart. Compatibility of the experimental results
      with two feasible models was investigated. In Model 1, ingested vitamin C enters
      a pre-existing pool before absorption, which occurs only when a threshold is
      exceeded; in Model 2, ingested vitamin C is exchanged with a pre-existing flux
      before absorption. The key difference between these two models lies in the
      predicted profile of labelled material in plasma. Model 1 predicts that the
      second unlabelled dose will produce a secondary release of labelled vitamin C
      which will not be observed on the basis of Model 2. In all subjects Model 1
      failed to predict the observed plasma concentration profiles for labelled and
      unlabelled vitamin C, but Model 2 fitted the experimental observations. We
      speculate on possible physiological explanations for this behaviour, but from the
      limited information available cannot unequivocally confirm the model structure by
      identifying the source of the supposed flux.

PMID- 15975162
TI  - Concentrations of cholesterol oxidation products in raw, heat-processed and
      frozen-stored meat of broiler chickens fed diets differing in the type of fat and
      vitamin E concentrations.
AB  - The present study was performed to investigate the effect of dietary fat and
      vitamin E on concentrations of cholesterol oxidation products (COP) in broiler
      muscle. A total of 144 1-d-old broiler chicks were fed diets with either palm
      oil, soyabean oil or linseed oil and vitamin E concentrations of 20, 40 or 200
      mg/kg for 35 d. COP concentrations were analysed in raw, heat-processed (180
      degrees C, 20 min) and frozen-stored (-20 degrees C, 6 months) breast and thigh
      muscles. COP concentrations were influenced by dietary vitamin E concentration,
      dietary fat, treatment and type of muscle (P<0.001). Increasing the dietary
      vitamin E concentration generally reduced the concentration of COP. This effect
      was strongest in broilers fed linseed oil and weakest in broilers fed palm oil;
      the effect of vitamin E was also stronger in heated muscles than in raw or frozen
      stored muscles. Moreover, the concentration of COP in thigh muscle was more
      strongly influenced by dietary vitamin E than that in breast muscle. COP
      concentrations in muscles were on average highest in broilers fed linseed oil and
      lowest in broilers fed palm oil, but the effect of the dietary fat also depended
      on the vitamin E concentration, the treatment and the type of muscle. In
      conclusion, our study shows that dietary fat and vitamin E influence the
      concentrations of total COP in broiler muscle. However, the effects of these
      factors were not only influenced by interactions between each other, but also
      depended on the treatment of the muscle and the type of muscle.

PMID- 15975163
TI  - Diabetes-prone BioBreeding rats do not have a normal immune response when weaned
      to a diet containing fermentable fibre.
AB  - Diet is known to modulate the development of diabetes in diabetes-prone
      BioBreeding (BBdp) rats. The objective of the present study was to determine the
      effect of fermentable fibre (FF) on immune function in BBdp and diabetes
      resistant BioBreeding (BBdr) rats after weaning. Weanling BBdp (thirty-six to
      thirty-eight per diet) and BBdr rats (thirty to thirty-two per diet) were fed a
      nutritionally complete, semi-purified, casein-based diet containing either
      cellulose (control diet, 8 % w/w) or FF (3.2 % cellulose+4.8 % w/w inulin). At 35
      d, the small intestine was excised and lymphocytes isolated from spleen,
      mesenteric lymph nodes and Peyer's patches. Feeding FF to both BBdr and BBdp rats
      affected the production of anti-inflammatory cytokines (P=0.02). In BBdr rats,
      feeding FF compared with cellulose resulted in an increased small intestinal
      length (P=0.0031), higher proliferative (stimulation) index from both splenocytes
      (P=0.001) and mesenteric lymph nodes (P=0.04), and an increased proportion of
      CD8+ T-cells in the Peyer's patches (P=0.003). We did not observe an effect of
      diet on the number of IgA-bearing cells in the jejunum from BBdr rats. Feeding FF
      to BBdp rats did not affect the same parameters. BBdp rats had both a higher
      proportion of B-cells in the Peyer's patches (P=0.01) and a higher number of IgA+
      cells in the jejunum (P=0.0036) when fed a diet containing FF, a response not
      observed in BBdr rats. We demonstrate that several aspects of the BBdp immune
      system respond differently than that of BBdr rats when challenged at weaning with
      FF.

PMID- 15975164
TI  - The effects of vitamin E supplementation on autoimmune-prone New Zealand black x
      New Zealand white F1 mice fed an oxidised oil diet.
AB  - The purpose of the present study was to investigate the effect of vitamin E
      supplementation on autoimmune disease in New Zealand blackxNew Zealand white F1
      (NZB/W F1) female mice fed an oxidised oil diet. First, 5-month-old mice were fed
      an AIN-76 diet containing either 150 g fresh soyabean oil/kg (15S), 50 g fresh
      soyabean oil/kg + 100 g oxidised frying oil/kg (5S10F) or 5S10F supplemented with
      all-rac-alpha-tocopheryl acetate at 275 mg/kg diet level (5S10F5E) or 550 mg/kg
      (5S10F10E), respectively, in experiment 1. The results showed that mice fed the
      5S10F10E diet had a lower anti-double-stranded DNA IgG antibody level and a
      longer lifespan than those fed the 15S and 5S10F diets. Therefore, the 5S10F and
      5S10F10E treatments were repeated in experiment 2 for further analysis. The
      results showed that vitamin E supplementation in the oxidised oil significantly
      decreased thiobarbituric acid-reactive substance values in the kidney and spleen
      of NZB/W F1 mice. Interferon-gamma and IL-6 production by mitogen-stimulated
      splenocytes decreased in mice fed the 5S10F10E diet, whereas the secretion of IL
      2 and IL-10 was not affected. The percentage of T-cells was significantly higher
      and that of MHC class II-bearing cells was lower in the spleens of the 5S10F10E
      group. The 5S10F10E group had a significantly higher linoleic acid (18 : 2n-6)
      composition than the 5S10F diet group. Therefore, vitamin E supplementation in
      oxidised oil might decrease oxidative stress, anti-double-stranded DNA IgG
      antibody, regulate cytokines and lymphocyte subsets, and subsequently alleviate
      the severity of autoimmune disease such as systemic lupus erythematosus under
      oxidative stress.

PMID- 15975165
TI  - Bone status in an animal model of chronic sub-optimal nutrition: a morphometric,
      densitometric and mechanical study.
AB  - In children, inappropriate eating habits can induce a disease known as
      nutritional dwarfing (ND). Due to the link between nutritional condition and bone
      growth, the effects induced by a 20 % reduction of food intake on bone competence
      were assessed in an animal model of ND. Bone status during catch-up growth was
      also analysed. Male Wistar rats were divided into control (C) and ND groups. C
      rats were fed ad libitum. ND received 80 % of the diet consumed by C for 4 weeks
      (T4); thereafter, they were fed ad libitum for 8 weeks. Results, expressed as
      mean (SEM) for ND v. C, were as follows. At T4, body weight (g) and length (cm)
      and femur weight (g) and length (mm) were 97.35 (SEM 5.89) v. 199.07 (SEM 9.24),
      16.91 (SEM 0.41) v. 20.26 (SEM 0.31), 0.30 (SEM 0.01) v. 0.46 (SEM 0.01) and
      23.09 (SEM 0.29) v. 26.98 (SEM 0.26), respectively (P<0.001); bone mineral
      content (g) and density (g/cm(2)) were 0.014 (SEM 0.002) v. 0.030 (SEM 0.002) and
      0.061 (SEM 0.004) v. 0.080 (SEM 0.003), respectively (P<0.001); load-bearing
      capacity (N), yielding load (N) and elastic stiffness (N/mm) were 25.06 (SEM
      1.24) v. 50.34 (SEM 2.94), 23.72 (SEM 1.02) v. 46.97 (SEM 1.75) and 65.98 (SEM
      4.42) v. 115.07 (SEM 3.85), respectively (P<0.001); cross-sectional area (mm(2))
      and moment of inertia (mm(4)) were 2.86 (SEM 0.19) v. 4.54 (SEM 0.17) and 1.27
      (SEM 0.08) v. 3.03 (SEM 0.16), respectively (P<0.001). Significant effects were
      not evident in material properties. Parameters assessed normalized during re
      feeding. These results suggest that the impaired mechanical femur competence in
      ND rats could be due to an altered bone mass and architectural distribution
      rather than to intrinsic quality. Re-feeding caused a reversal of the effects of
      food restriction on growth and bone parameters in ND rats.

PMID- 15975166
TI  - Validation of energy intake by 24-hour multiple pass recall: comparison with
      total energy expenditure in children aged 5-7 years.
AB  - Accurate measurement of energy intake (EI) is essential in studies of energy
      balance in all age groups. Reported values for EI can be validated against total
      energy expenditure (TEE) measured using doubly labelled water (DLW). Our previous
      work has indicated that the use of the standardized 24 h multiple pass recall (24
      h MPR) method produces slight overestimates of EI in pre-school children which
      are inaccurate at individual level but acceptable at group level. To extend this
      work, the current study validated EI by 24 h MPR against TEE by DLW in sixty
      three (thirty-two boys) school-aged children (median age 6 years). In both boys
      and girls, reported EI was higher than TEE, although this difference was only
      significant in the girls (median difference 420 kJ/d, P=0.05). On analysis of
      agreement between TEE and EI, the group bias was an overestimation of EI by 250
      kJ/d with wide limits of agreement (-2880, 2380 kJ/d). EI was over-reported
      relative to TEE by 7 % and 0.9 % in girls and boys, respectively. The bias in the
      current study was lower than in our previous study of pre-school children,
      suggesting that estimates of EI become less inaccurate as children age. However,
      the current study suggests that the 24 h MPR is inaccurate at the individual
      level.

PMID- 15975167
TI  - Brussels sprouts, inulin and fermented milk alter the faecal microbiota of human
      microbiota-associated rats as shown by PCR-temporal temperature gradient gel
      electrophoresis using universal, Lactobacillus and Bifidobacterium 16S rRNA gene
      primers.
AB  - We investigated the effect of Brussels sprouts, inulin and a fermented milk on
      the faecal microbiota diversity of human microbiota-associated (HMA) rats by PCR
      temporal temperature gradient gel electrophoresis (PCR-TTGE) using universal and
      group-specific 16S rRNA gene primers. The HMA rats were submitted to a control
      diet for 10 d (initial time), then switched to the experimental diets for 4 weeks
      (final time). Using universal primers, the mean degree of similarity between all
      faecal samples at initial time was 80.8 %. In the group consuming the control
      diet throughout the experiment, the mean degree of similarity between the PCR
      TTGE profiles at initial v. final time was 76.8 %, reflecting a spontaneous
      temporal variation. The mean degree of similarity between control and
      experimental groups at final time was lower, 72.4 %, 74.4 % and 75.6 % for
      inulin, Brussels sprouts and fermented milk, respectively, indicating a dietary
      effect on the predominant populations. Using specific primers, bifidobacteria
      could be detected only in those rats that had consumed inulin, showing a specific
      increasing effect of this dietary compound. The Lactobacillus population was very
      heterogeneous at initial time but tended to homogenize within each dietary group.
      At final time, caecal contents were collected for analysis of SCFA and beta
      glucuronidase activity. Inulin and Brussels sprouts increased the butyrate and
      acetate proportion, respectively, while the fermented milk did not modify the
      caecal biochemistry. This experiment shows for the first time that cruciferous
      vegetables are able to alter the diversity and the metabolic activities of the
      digestive microbiota in HMA rats.

PMID- 15975168
TI  - Pregnancy increases urinary loss of carnitine and reduces plasma carnitine in
      Korean women.
AB  - This study compared plasma and urinary carnitine concentrations in pregnant and
      non-pregnant Korean women. The subjects were fifty pregnant women and thirty non
      pregnant women aged 24-28 years. During the first trimester, dietary carnitine
      intakes in the pregnant women were much lower than in non-pregnant women (70.00
      (SD 29.22) micromol/d), but over the course of pregnancy carnitine intake
      increased from 44.64 (SD 24.84) micromol/d during the first trimester to 96.11
      (SD 36.56) micromol/d during the third trimester. Pregnant women had a
      significantly lower plasma carnitine concentration than non-pregnant women.
      Plasma concentrations of non-esterified carnitine, acid-soluble acylcarnitine and
      total carnitine were significantly lower during the second and third trimesters
      than the first. Plasma acid-insoluble acylcarnitine levels, which tended to be
      higher in the non-pregnant women compared with the pregnant women, increased
      significantly as gestation proceeded. The urinary excretion of non-esterified
      carnitine, acid-soluble acylcarnitine and total carnitine was significantly
      higher in the pregnant women during the first and second trimesters than in non
      pregnant women and decreased significantly as gestation proceeded. We found that
      there was a significant decrease in plasma carnitine level even though dietary
      carnitine intake increased as gestation proceeded. The low urinary excretion of
      carnitine in late pregnancy may be caused by an increased demand during
      pregnancy.

PMID- 15975169
TI  - Acute effects of meal fatty acids on postprandial NEFA, glucose and apo E
      response: implications for insulin sensitivity and lipoprotein regulation?
AB  - Our aim was to determine whether meal fatty acids influence insulin and glucose
      responses to mixed meals and whether these effects can be explained by variations
      in postprandial NEFA and Apo, which regulate the metabolism of triacylglycerol
      rich lipoproteins (Apo C and E). A single-blind crossover study examined the
      effects of single meals enriched in saturated fatty acids SFA), n-6 PUFA and MUFA
      on plasma metabolite and insulin responses. The triacylglycerol response
      following the PUFA meal showed a lower net incremental area under the curve than
      following the SFA and MUFA meals (P<0.007). Compared with the SFA meal, the PUFA
      meal showed a lower net incremental area under the curve for the NEFA response
      from initial suppression to the end of the postprandial period (180-480 min;
      P<0.02), and both PUFA and MUFA showed a lower net incremental glucose response
      (P<0.02), although insulin concentrations were similar between meals. The pattern
      of the Apo E response was also different following the SFA meal (P<0.02). There
      was a significant association between the net incremental NEFA (180-480 min) and
      glucose response (rs=0.409, P=0.025), and in multiple regression analysis the
      NEFA response accounted for 24 % of the variation in glucose response. Meal SFA
      have adverse effects on the postprandial glucose response that may be due to
      greater elevations in NEFA arising from differences in the metabolism of SFA- v.
      PUFA- and MUFA-rich lipoproteins. Elevated Apo E responses to high-SFA meals may
      have important implications for the hepatic metabolism of triacylglycerol-rich
      lipoproteins.

PMID- 15975170
TI  - Determinants of plasma dihydrophylloquinone in men and women.
AB  - Commercial hydrogenation results in the formation of trans fatty acids. An
      unintended consequence of the hydrogenation process is conversion of
      phylloquinone (vitamin K1) to dihydrophylloquinone. Plasma dihydrophylloquinone
      concentrations have yet to be characterized in population-based studies. Dietary
      determinants of plasma dihydrophylloquinone were estimated using a semi
      quantitative food frequency questionnaire in 803 men and 913 women in the
      Framingham Offspring Study. Geometric mean dihydrophylloquinone intake was 21.3
      (95 % CI 20.4, 22.3) microg/d in men and 19.4 (95 % CI 18.5, 20.2) microg/d in
      women. Detectable (>0.05 nmol/l) plasma dihydrophylloquinone concentrations were
      measured in 41 % and 30 % of men and women, respectively. The multivariate odds
      ratio (OR) of detectable plasma dihydrophylloquinone from the lowest to the
      highest quartile category of dihydrophylloquinone intake were 1 (referent), 1.13
      (95 % CI 0.83, 1.53), 1.66 (95 % CI 1.21, 2.26) and 1.84 (95 % CI 1.31, 2.58), P
      for trend <0.001, adjusted for sex, age, body mass index, triacylglycerols,
      season and energy intake. Higher trans fatty acid intake was associated with
      higher multivariate OR for detectable plasma dihydrophylloquinone (OR comparing
      extreme quartiles 2.41 (95 % CI 1.59, 3.64), P for trend <0.001). There were
      limitations in the use of plasma dihydrophylloquinone, evident in the high
      proportion of the population that had non-detectable dihydrophylloquinone
      concentrations. Despite this caveat, higher plasma dihydrophylloquinone was
      associated with higher dihydrophylloquinone intake and higher trans fatty acid
      intake.

PMID- 15975171
TI  - Comparison of two statistical approaches to predict all-cause mortality by
      dietary patterns in German elderly subjects.
AB  - Dietary patterns are comprehensive variables of dietary intake appropriate to
      model the complex exposure in nutritional research. The objectives of this study
      were to identify dietary patterns by applying two statistical methods, principal
      component analysis (PCA) and reduced rank regression (RRR), and to assess their
      ability to predict all-cause mortality. Motivated by previous studies we chose
      percentages of energy from different macronutrients as response variables in the
      RRR analysis. We used data from 9356 German elderly subject enrolled in the
      European Prospective Investigation into Cancer and Nutrition study. The first RRR
      pattern, subjects which explained 30.8 % of variation in energy sources and
      especially much variation in intake of saturated fat, monounsaturated fat and
      carbohydrates was a significant predictor of all-cause mortality. The pattern
      score had high positive loadings in all types of meat, butter, sauces and eggs,
      and was inversely associated with bread and fruits. After adjustment for other
      known risk factors, the relative risks from the lowest to highest quintiles of
      the first RRR pattern score were 1.0, 1.01, 0.96, 1.32, 1.61 (P for trend:
      0.0004). In contrast, the first two PCA patterns explaining 19.7 % of food intake
      variation but only 7.0 % of variation in energy sources were not related to
      mortality. These results suggest that variation in macronutrients is meaningful
      for mortality and that the RRR method is more appropriate than the classic PCA
      method to identify dietary patterns relevant to mortality.

PMID- 15975172
TI  - Effects of L-carnitine supplementation on milk production, litter gains and back
      fat thickness in sows with a low energy and protein intake during lactation.
AB  - The present study investigated the effect of L-carnitine supplementation during
      pregnancy (125 mg/d) and lactation (250 mg/d) on milk production, litter gains
      and back-fat thickness in sows fed a low-energy and low-protein diet during
      lactation. Sows supplemented with L-carnitine produced more milk on days 11 and
      18 of lactation (+18 %; P<0.05) and had higher litter gains during suckling (+20
      %; P<0.01) than control sows. Loss of body weight during lactation was similar in
      both groups, but sows supplemented with L-carnitine had a greater reduction of
      back-fat thickness (+45 %; P<0.05) during lactation than control sows. In
      conclusion, this study shows that L-carnitine increases milk production and
      litter gains in sows in a strongly negative energy and N balance, and enhances
      body fat mobilisation.

PMID- 15975173
TI  - Some aspects of the pyridoxine (vitamin B6) requirement in weanling piglets.
AB  - Four trials were carried out to determine the optimal level of dietary pyridoxine
      (vitamin B6) and its interaction with riboflavin (vitamin B2) in early-weaned
      piglets. In Trial 1, twelve piglets were tube-fed graded supplements of B6, 0,
      10, 50 or 100 mg/kg. The level of 50 mg/kg maximized B6 in red blood cells
      (P<0.05). In Trial 2, thirty-six piglets were tube-fed with four combinations of
      B6 (0 v. 50 mg/kg) and B2 (0 v. 25 mg/kg). The B6 supplement increased (P<0.01)
      B6 in red blood cells. C-peptide and insulin responses to intravenous glucose
      tended (P<0.08) to or decreased (P<0.03) with B2 while no effect was observed on
      glucose. After gastro-enteral glucose, dietary B2 depressed C-peptide and insulin
      responses in B6-unsupplemented piglets and increased them in B6-supplemented
      piglets (P<0.03). The glucose response tended to be higher in B6-supplemented
      piglets (P<0.06). Trials 3 and 4 were carried out in commercial conditions using
      either B6 and/or B2 supplements given during 2 weeks after weaning (Trial 3) or a
      B6 supplement alone (50 mg/kg) given between 2 (weaning) and 10 weeks of age.
      Despite a marked and persistent increase (P<0.01) of B6 in red blood cells in B6
      supplemented piglets, the effect on growth performance was either none (P>0.39;
      Trial 3) or marginally lower (<-2 %; P<0.03; Trial 4). In conclusion, it appears
      that a dietary supplement of 50 mg/kg B6 saturated the red blood cell pool in B6
      and influenced, along with B2, the glucose homeostasis through the entero-insular
      axis. Nevertheless, such metabolic effects are not reflected on growth
      performance.

PMID- 15975174
TI  - Effect of consumption of soy isoflavones on behavioural, somatic and affective
      symptoms in women with premenstrual syndrome.
AB  - Up to 80 % of the Western female population experience premenstrual syndrome
      (PMS). Long-term pharmacological therapy is unacceptable to most women, and is
      not warranted for moderate symptoms. Nutritional therapies are popular, but lack
      a clear evidence base. Anecdotal evidence suggests beneficial effects of soy
      isoflavones because of their influence on endogenous oestrogen and actions on
      specific tissues. The effect of isolated soya protein (ISP) containing 68 mg/d
      (aglycone equivalents) soy isoflavones (IF) on premenstrual symptom severity was
      studied in a seven-menstrual cycle, double-blind, placebo-controlled, crossover
      intervention study in twenty-three women with prospectively confirmed PMS aged 18
      35 years and BMI 19-30 kg/m(2). ISP containing IF or milk protein placebo was
      consumed for two complete menstrual cycles. ISP containing IF (genistein,
      daidzein, equol) were measured in 24 h urine samples. After two cycles of ISP
      containing IF intervention, total symptoms (F(2,36) 8.20, P=0.000) and physical
      symptoms (F(2,36) 8.18, P=0.000) were significantly reduced compared with
      baseline after both active and placebo treatments, although differences between
      active and placebo treatment were non-significant. Specific premenstrual
      symptoms, headache (F(2,32) 4.10, P=0.026) and breast tenderness (F(2,32) 4.59,
      P=0.018), were reduced from baseline after soy IF, but not milk protein placebo.
      Cramps (F(2,32) 4.15, P=0.025) and swelling (F(2,32) 4.64, P=0.017) were
      significantly lower after active treatment compared with placebo. Concentrations
      of genistein and daidzein were increased following soy IF consumption, but equol
      production did not enhance symptom reduction. The present study showed that ISP
      containing IF may have potential to reduce specific premenstrual symptoms via non
      classical actions.

PMID- 15975175
TI  - Age and gender differences in children's food preferences.
AB  - The present study was conducted to examine the developmental patterning of food
      preferences in a large sample of British schoolchildren and to investigate
      possible gender differences. Using a cross-sectional survey design, the study was
      carried out in three primary and three secondary schools in West London, UK. A
      total of 1291 children aged from 4 to 16 years completed a 115-item food
      preference questionnaire in class time, supervised by class teachers and
      assistants. Children indicated whether they had ever tried each item and, if so,
      how much they liked it. We observed age-related increases in the number of foods
      tried (P<0.001), liked (P<0.005) and disliked (P<0.05). Controlling for the
      number of foods tried rendered the increase in dislikes non-significant and
      reversed the age effect on the number liked. Girls liked fruit (P<0.05) and
      vegetables (P<0.001) more than boys did; boys liked fatty and sugary foods
      (P<0.005), meat (P<0.001), processed meat products (P<0.001) and eggs (P<0.05)
      more than girls did. Some age differences were apparent in liking for categories
      of food, although the effects were not linear. Across ages and genders, children
      rated fatty and sugary foods most highly, although ratings for fruit were also
      high. Children's food preferences overall are not consistent with a healthy diet.
      Interventions should focus on increasing the familiarity, availability and
      accessibility of healthy foods and should be mindful of the need to target
      messages appropriately for boys who have less healthful food preferences than
      girls at all ages.

PMID- 15975176
TI  - Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated
      with lower tissue triglyceride and higher plasma catecholamines.
AB  - Slower weight gain and less visceral fat had been observed when rats fed a high
      fat diet were supplemented with freeze-dried bitter melon (BM) juice; the
      metabolic consequences and possible mechanism(s) were further explored in the
      present study. In a 4-week experiment, rats were fed a low-fat (70 g/kg) or a
      high-fat (300 g/kg) diet with or without BM (7.5 g/kg or 0.75%). BM-supplemented
      rats had lower energy efficiency, visceral fat mass, plasma glucose and hepatic
      triacylglycerol, but higher serum free fatty acids and plasma catecholamines. In
      the second experiment, 7-week BM supplementation in high-fat diet rats led to a
      lowering of hepatic triacylglycerol (P<0.05) and steatosis score (P<0.05) similar
      to those in rats fed a low-fat diet. BM supplementation did not affect serum and
      hepatic cholesterol. However, plasma epinephrine and serum free fatty acid
      concentrations were increased (P<0.05). In the third experiment, BM(7.5 and 15
      g/kg) and 1.5 % BM lowered triacylglycerol concentration in red gastrocnemius and
      tibialis anterior (P<0.05) muscle, but a dose-response effect was not observed.
      These data suggest that chronic BM feeding leads to a general decrease in tissue
      fat accumulation and that such an effect is mediated in part by enhanced
      sympathetic activity and lipolysis. BM or its bioactive ingredient(s) could be
      used as a dietary adjunct in the control of body weight and blood glucose.

PMID- 15975177
TI  - Meat consumption trends and health: casting a wider risk assessment net.

PMID- 15975178
TI  - Nutritional science for this century.

PMID- 15975179
TI  - Public health implications of meat production and consumption.
AB  - The high level of meat and saturated fat consumption in the USA and other high
      income countries exceeds nutritional needs and contributes to high rates of
      chronic diseases such as cardiovascular disease, diabetes mellitus and some
      cancers. Affluent citizens in middle- and low-income countries are adopting
      similar high-meat diets and experiencing increased rates of these same chronic
      diseases. The industrial agricultural system, now the predominant form of
      agriculture in the USA and increasingly world-wide, has consequences for public
      health owing to its extensive use of fertilisers and pesticides, unsustainable
      use of resources and environmental pollution. In industrial animal production
      there are public health concerns surrounding feed formulations that include
      animal tissues, arsenic and antibiotics as well as occupational health risks and
      risks for nearby communities. It is of paramount importance for public health
      professionals to become aware of and involved in how our food is produced.

PMID- 15975180
TI  - The role of foreign direct investment in the nutrition transition.
AB  - OBJECTIVE: To examine the role of foreign direct investment (FDI) in the
      nutrition transition, focusing on highly processed foods. DESIGN: Data on FDI
      were identified from reports/databases and then compiled and analysed. A review
      of published literature on FDI into the food sector was conducted. SETTING: The
      nutrition transition is a public health concern owing to its connection with the
      rising burden of obesity and diet-related chronic diseases in developing
      countries. Global health leaders are calling for action to address the threat.
      Highly processed foods often have considerable fat, sugar and salt content, and
      warrant closer examination. RESULTS: FDI into food processing, service and retail
      has risen rapidly since the 1980s, mainly from transnational food companies
      (TFCs) in developed countries. As FDI has risen, so has the proportion invested
      in highly processed foods for sale in the host market. FDI has proved more
      effective than trade in generating sales of highly processed foods, and enables
      TFCs to cut costs, gain market power and obtain efficiencies in distribution and
      marketing. The amount of FDI targeted at developing countries is increasing;
      while a disproportionate share enters the larger developing economies, foreign
      affiliates of TFCs are among the largest companies in low- and low- to middle
      income countries. The effect of FDI is to make more highly processed foods
      available to more people. FDI has made it possible to lower prices, open up new
      purchasing channels, optimise the effectiveness of marketing and advertising, and
      increase sales. CONCLUSION: FDI has been a key mechanism in shaping the global
      market for highly processed foods. Notwithstanding the role of demand-side
      factors, it has played a role in the nutrition transition by enabling and
      promoting the consumption of these foods in developing countries. Empirical data
      on consumption patterns of highly processed foods in developing countries are
      critically needed, but since FDI is a long-term investment vehicle, it is
      reasonable to assume that availability and consumption of highly processed foods
      will continue to increase. FDI can, however, bring considerable benefits as well
      as risks. Through its position 'upstream', FDI would therefore be an appropriate
      entry-point to implement a range of public health policies to 'redirect' the
      nutrition transition.

PMID- 15975181
TI  - Nutrition education for illiterate children in southern Madagascar--addressing
      their needs, perceptions and capabilities.
AB  - OBJECTIVE: A Knowledge, Attitudes and Practices (KAP) study was conducted in
      three villages of Bekily District in southern Madagascar prior to the
      implementation of a health education programme with children. The participatory
      learning concept of the Child-to-Child approach was followed to involve the
      children in the planning and implementation of the programme, which was covered
      by the German Agency for Technical Cooperation. DESIGN: To this effect,
      qualitative research methods such as Participatory Learning and Action techniques
      (focus group discussions, mapping and matrix ranking, etc.) were applied.
      SUBJECTS: The survey was conducted between August and December 1999. It involved
      a total of 55 school-aged children (6-14 years) along with 21 mothers and 34
      fathers, representing different ethnic groups and educational backgrounds.
      RESULTS: The results show that children's KAP related to health and nutrition
      strongly reflect those of adults. They are not aware of a possible link between
      bad hygiene and the occurrence of diseases. According to them, diarrhoea or
      malaria is caused by consuming too large amounts of certain foods. Even if they
      know about certain elementary hygiene behaviours, they do not practise this in
      their everyday life. CONCLUSION: A major objective of the health education
      programme for children should be to tackle the discrepancy between hygiene
      related knowledge and behaviour. Through the participatory study approach the
      children revealed their ability to contribute to the programme development. In
      using appropriate communication channels, the Child-to-Child health education
      programme is expected to influence the health behaviours of both adults and
      children. The health education programme should be combined with a literacy
      programme to address the children's desire to learn reading and writing.

PMID- 15975182
TI  - Complementary foods consumed by 6-12-month-old rural infants in South Africa are
      inadequate in micronutrients.
AB  - OBJECTIVE: To determine the nutrient composition of complementary foods consumed
      by 6-12-month-old South African infants. DESIGN: Nutrient intake was determined
      for infants who were recruited to participate in a randomised controlled trial
      using a single 24-hour dietary recall. SETTING/SUBJECTS: Infants aged 6-12 months
      (n=475) residing in The Valley of a Thousand Hills, a rural area in KwaZulu
      Natal, South Africa. RESULTS: Energy and protein intakes from complementary foods
      were adequate. Infants who consumed infant products (commercially available
      fortified infant cereals/ready-to-eat canned baby foods/formula milk powder) had
      significantly higher intakes of calcium, iron, zinc, vitamin A, thiamine,
      riboflavin, niacin, vitamin B6, vitamin B12 and vitamin C than infants who did
      not consume any infant products. For infants who consumed infant cereals (n=142),
      these cereals provided 51% of total iron intake. Infant cereals provided more
      than 25% of total intake for magnesium, thiamine, niacin and vitamin B12. For
      infants consuming ready-to-eat canned baby foods (n=77), these products
      contributed less than 15% of total intake for all the micronutrients. The
      nutrient density of the complementary diet was less than half the desired density
      for calcium, iron and zinc. Animal products were consumed by 17% of infants, 26%
      consumed dairy products and 18% consumed vitamin-A-rich fruit and vegetables
      during the 24-hour recall period. CONCLUSION: The nutrient composition of
      complementary foods among rural South African infants was inadequate, especially
      for iron, zinc and calcium. Strategies should be developed to improve the
      nutritional quality of their diets.

PMID- 15975183
TI  - Knowledge of iodine nutrition in the South African adult population.
AB  - OBJECTIVES: To determine the level of knowledge regarding iodine nutrition and
      its relationship with socio-economic status in the South African population.
      DESIGN: A cross-sectional population survey collecting questionnaire information
      on knowledge of iodine nutrition and sociodemographic variables in a multistage,
      stratified, cluster study sample, representative of the adult South African
      population. SETTING: Home visits and personal interviews in the language of the
      respondent. SUBJECTS: Data were collected from one adult in each of the selected
      2164 households, and the participation rate was 98%. RESULTS: Only 15.4% of
      respondents correctly identified iodised salt as the primary dietary source of
      iodine, 16.2% knew the thyroid gland needs iodine for its functioning, and a mere
      3.9% considered brain damage, and 0.8% considered cretinism, as the most
      important health consequence of iodine deficiency. Compared with respondents from
      high socio-economic households, respondents from low socio-economic households
      were considerably less informed about aspects of iodine nutrition covered in this
      study. CONCLUSIONS: The knowledge level of iodine nutrition is low among South
      Africans, particularly among the low socio-economic groups. These data suggest
      that the international emphasis on brain damage resulting from iodine deficiency
      has not been conveyed successfully to the consumer level in this country.

PMID- 15975184
TI  - Women's iodine status and its determinants in an iodine-deficient area in the
      Kayes region, Mali.
AB  - OBJECTIVE: To assess iodine status and its determinants in women of childbearing
      age in a rural area in the Kayes region, Mali, West Africa. DESIGN: Cross
      sectional study where women's iodine status was indicated by urinary iodine
      concentration (UIC) and level of goitre based on palpation. Salt iodine was
      assessed semi-quantitatively at household level. Individual characteristics were
      collected using questionnaires. SETTING: Fifteen villages in a rural area in the
      Kayes region of Mali. SUBJECTS: Women aged 15-45 years (n=423). RESULTS: Median
      UIC was 2.7 microg dl(-1), and only 6% of the women had adequate iodine status of
      UIC >10 microg dl(-1). Most women (60%) had visible goitre, and only 9% were
      classified as without goitre. Only 39% of the households were using salt with any
      iodine, and level of knowledge about salt iodisation was low. Main determinants
      of UIC were breast-feeding and level of salt iodisation; currently breast-feeding
      women had lower UIC, and UIC increased with increasing level of iodine in
      household salt. Prevalence of goitre was lower in older women with higher body
      mass index. CONCLUSION: The study indicates severe iodine deficiency in the study
      area. Urgent action is needed to improve the situation through enforcing salt
      iodisation legislation and increasing the level of knowledge about the importance
      of iodised salt in the population.

PMID- 15975186
TI  - Mortality attributable to higher-than-optimal body mass index in New Zealand.
AB  - OBJECTIVES: To estimate the burden of mortality in New Zealand due to higher-than
      optimal body mass index (BMI) in 1997, as well as mortality that could be avoided
      in 2011 with feasible changes in mean population BMI. SETTING: New Zealand.
      DESIGN: Comparative risk assessment methodology was used to estimate the
      attributable and avoidable mortality due to high BMI. Outcomes assessed were
      ischaemic heart disease (IHD), ischaemic stroke, type 2 diabetes mellitus,
      colorectal cancer and postmenopausal breast cancer. RESULTS: In 1997, 3154 deaths
      (11% of all deaths) in New Zealand were due to higher-than-optimal BMI (>21 kg m(
      2)). This amounted to 83% of diabetes deaths, 24% of IHD deaths, 15% of ischaemic
      stroke deaths and 4% of all cancer deaths. If the projected increase in mean
      population BMI by 2011 was limited to 1.0 kg m(-2) rather than 1.3 kg m(-2),
      approximately 385 deaths could be prevented annually, mainly from diabetes.
      CONCLUSIONS: These results quantify the importance of higher-than-optimal BMI as
      a major modifiable cause of premature death in New Zealand. Intervention policies
      that would have only modest effects on slowing the rate of increase in mean
      population BMI by 2011 could still prevent hundreds of deaths annually.

PMID- 15975185
TI  - Nutrition and the burden of disease in New Zealand: 1997-2011.
AB  - OBJECTIVE: To estimate the burden of disease due to selected nutrition-related
      risk factors (high total blood cholesterol, high systolic blood pressure, high
      body mass index (BMI) and inadequate vegetable and fruit intake) in 1997, as well
      as the burden that could potentially be avoided in 2011 if small, favourable
      changes in the current risk factor distribution were to occur. DESIGN: Data on
      risk factor levels, disease burden and risk associations were combined using
      comparative risk assessment methodology, a systematic approach to estimating both
      attributable and avoidable burden of disease. Disease outcomes assessed varied
      according to risk factor and included ischaemic heart disease, stroke, type 2
      diabetes mellitus and selected cancers. SETTING: New Zealand. RESULTS:
      Approximately 4500 deaths (17% of all deaths) in 1997 were attributable to high
      cholesterol, 3500 (13%) to high blood pressure, 3000 (11%) to high BMI and 1500
      (6%) to inadequate vegetable and fruit intake. Taking prevalence overlap into
      account, these risk factors were estimated jointly to contribute to approximately
      11 000 (40%) deaths annually in New Zealand. Approximately 300 deaths due to each
      risk factor could potentially be avoided in 2011 if modest changes were made to
      each risk factor distribution. CONCLUSIONS: High cholesterol, blood pressure and
      BMI, as well as inadequate vegetable and fruit intake, are major modifiable
      causes of death in New Zealand. Small changes in the population distribution of
      these risk factors could have a major impact on population health within a
      decade.

PMID- 15975187
TI  - Longitudinal changes in dietary intake in Scottish women around the menopause:
      changes in dietary pattern result in minor changes in nutrient intake.
AB  - OBJECTIVE: To examine dietary change that has occurred over 5 to 6 years.
      SUBJECTS: A cohort of Scottish women (n=898) with a mean age of 47.5 years (range
      45-54 years) at baseline. DESIGN: Dietary intake was assessed by validated food
      frequency questionnaire (FFQ) and analysed using the UK Composition of Foods
      database. RESULTS: Since the first dietary assessment, mean daily energy intake
      had decreased from 8.2+/-2.3 to 7.9+/-2.2 MJ. The degree of low energy reporting
      (defined as ratio of energy intake to basal metabolic rate <1.1) had increased
      from 18.7% at baseline to 25.6% at follow-up. Low energy reporters were
      significantly heavier than 'normal' energy reporters (mean weight at follow-up,
      68.9+/-12.6 vs. 66.8+/-11.3 kg) and could be deliberately restricting intake
      rather than underreporting. Overall there were decreases in intakes of red meat,
      processed meat and cheese, but increases in poultry and non-oily fish
      consumption. Consumption of bread, biscuits and cakes had gone down and there was
      an increase in cereal and rice/pasta consumption. Intake of potatoes had
      decreased whereas fruit intake had increased. There were small but statistically
      significant differences in intakes for most nutrients (<8% change). Nutrient
      intakes at both visits were similar across menopausal status and usage groups of
      hormone replacement therapy. Modifications to the computer version of the McCance
      and Widdowson nutrient database, which differed from the published version, were
      noted. These changes altered the original baseline values for our study.
      CONCLUSIONS: The menopause per se is not a period of marked change in nutrient
      intake. Caution is advised when using computer databases of food compositions for
      longitudinal studies.

PMID- 15975188
TI  - Breast-feeding initiation and exclusive duration at 6 months by social class-
      results from the Millennium Cohort Study.
AB  - OBJECTIVES: To assess breast-feeding initiation and rates of exclusive breast
      feeding for the first 6 months after birth, and to examine social class
      differences in breast-feeding rates. DESIGN: First sweep of a longitudinal
      population-based survey, the Millennium Cohort Study. SETTING: Four countries of
      the UK. SUBJECTS: Subjects were 18 125 singletons born over a 12-month period
      spanning 2000-01. Data were collected by parental interview on the initiation of
      breast-feeding and exclusivity at 1, 4 and 6 months after birth. RESULTS: Overall
      breast-feeding was initiated for 71% of babies, and by 1, 4 and 6 months of age
      the proportions being exclusively breast-fed were 34%, 3% and 0.3%, respectively.
      There were clear social class differences and mothers with routine jobs with the
      least favourable working conditions were more than four times less likely (odds
      ratio (OR) 0.22, 95% confidence interval (CI) 0.18-0.29) to initiate breast
      feeding compared with women in higher managerial and professional occupations.
      Women in routine jobs were less likely to exclusively breast-feed their infants
      at 1 month (OR 0.42, 95% CI 0.36-0.50) and 4 months (OR 0.5, 95% CI 0.31-0.77)
      compared with women in higher managerial and professional occupations.
      CONCLUSIONS: Clear social class differences in breast-feeding initiation and
      exclusivity for the first 4 months were apparent in this large UK sample. By 6
      months, less than 1% of babies were being exclusively breast-fed. A co-ordinated
      multi-faceted strategy is required to promote breast-feeding, particularly among
      lower-income women.

PMID- 15975189
TI  - Consumer perception versus scientific evidence about health benefits and safety
      risks from fish consumption.
AB  - OBJECTIVE: To investigate the gap between consumer perception and scientific
      evidence related to health benefits and safety risks from fish consumption.
      DESIGN: Consumer perceptions from a cross-sectional survey in March 2003 in
      Belgium were compared with scientific evidence based on a literature review.
      METHOD: A quota sampling procedure was used with age as quota control variable.
      Subjects completed a self-administered questionnaire including health benefit
      beliefs from fish, fish content and effect beliefs for nutrients and harmful
      substances. SUBJECTS: Adults (n=429), who were the main person responsible for
      food purchasing in the household (284 women; 145 men), aged 18-83 years, from
      different regional, education, family size and income groups. RESULTS: Fish is
      predominantly perceived as a healthy food that reduces risk for coronary heart
      disease, which corroborates scientific evidence. This perception is stronger
      among women than among men. In contrast with scientific evidence, 46% of the
      consumers believe that fish contains dietary fibre, whereas less than one-third
      is aware that fish contains omega-3 fatty acids and that this nutrient has a
      positive impact on human health. The gap between perception and evidence is
      larger among consumers with lower education. In general, consumers are better
      aware of the content and effect of harmful substances than of nutrients in fish.
      CONCLUSIONS: Despite conclusive evidence about the content and positive effect of
      omega-3 fatty acids in fish, related consumer awareness and beliefs are poor and
      often wrong. This study exemplifies the need for nutrition education and more
      effective communication about the health benefits of fish consumption.

PMID- 15975190
TI  - Comparison between household budget survey and 24-hour recall data in a
      nationally representative sample of Polish households.
AB  - OBJECTIVE: Household budget survey (HBS) data are used regularly for nutritional
      epidemiological purposes. The validity of HBS data, however, is not well
      established. The aim of this project was to compare HBS and individual nutrition
      survey (INS) data in a nationally representative sample of Polish households.
      DESIGN: Estimates of food consumption and nutrient intake were compared between
      household food acquisition data collected over 1 month and a single 24-hour
      recall collected from every household member in a nationally representative
      sample of Polish households surveyed between September and November 2000. To
      facilitate the comparison, INS food consumption data excluded food eaten away
      from home and were modified using a computer program to estimate food 'as
      purchased' (including disaggregation of recipe data) and to allow for wastage.
      SETTING: Poland. SUBJECTS: Participants were 3716 individuals in 1215 households
      (representing co-operation rates of 86.2% and 89.2%, respectively). RESULTS: Good
      agreement was shown between median estimates of foods such as potatoes,
      vegetables (including processed), meat, meat products and poultry, and animal
      fats (excluding butter), but agreement was poor for bread and rolls, fruit,
      vegetable fats and oils, eggs and six other food groups. Estimates of energy and
      nutrient intake were within +/-10% with the exceptions of polyunsaturated fats,
      potassium and vitamin C. CONCLUSIONS: Possible reasons for differences in
      findings between the two surveys include survey bias (e.g. social approval bias
      leading to overreporting of fruit), seasonal variations (e.g. high potato
      purchases between September and November) and aspects of the methodology (e.g.
      HBS data were based on records collected over 1 month, whereas 24-hour recall
      data were based on recalls collected from all household respondents on only 1 day
      and averaged for each household type). HBSs provide useful data for
      epidemiological research, but findings need to be interpreted in the light of
      other data regarding consumption, and numerous factors that may affect
      consumption need to be taken into account.

PMID- 15975191
TI  - Psychosis as a possible side-effect of treatment with glatiramer acetate.

PMID- 15975193
TI  - Use of growth charts.

PMID- 15975194
TI  - The meaning of food to breast cancer survivors.
AB  - Although a definitive relationship between diet and breast cancer remains
      controversial, many women adopt dietary change after diagnosis. To understand
      factors motivating dietary change, we explored the meanings that breast cancer
      survivors attached to food during recovery. Six women who were breast cancer
      survivors for six to 19 years participated in semi-structured interviews
      exploring personal meanings attached to food, dietary changes after diagnosis,
      factors influencing dietary change, and experiences with food in relation to
      breast cancer. Two distinct phases emerged. These corresponded to active
      treatment, when women used food to gain control, to cope, for comfort, and for
      hope, and to post-treatment, when the meanings that women attached to food were
      shaped by the perception of food's role in breast cancer causation. Women who
      believed that diet prevents a first diagnosis adopted change to prevent
      recurrence, while those who did not believe in the relationship between diet and
      breast cancer adopted change to improve health. In women with breast cancer, food
      can be an important coping mechanism. Women may benefit from counselling grounded
      in the meanings they attach to food over the recovery continuum.

PMID- 15975195
TI  - Development and validation of a food frequency questionnaire.
AB  - Regular diet monitoring requires a tool validated in the target population. A 73
      item, semiquantitative, self-administered food frequency questionnaire (FFQ), was
      adapted in French and English from the Block National Cancer Institute Health
      Habits and History Questionnaire. The FFQ was used to capture usual long-term
      food consumption among adults living in Quebec. A representative sample of adults
      aged 18 to 82 (57% female) was recruited by random digit dialling in the Montreal
      region. Approximately 64% of recruits completed and returned the instrument by
      mail (n=248). The FFQ was validated in a subsample (n=94, 61% female) using four
      nonconsecutive food records (FRs). Median energy intakes (in kcal) for men and
      women, respectively, were FFQ (total sample) 2,112 and 1,823, FFQ (subsample)
      2,137 and 1,752, and FR (subsample) 2,510 and 1,830. Spearman correlation
      analyses between FFQ and FR nutrients were positive (with r ranging from 0.32 for
      folate to 0.58 for saturated fatty acids) and statistically significant
      (p<0.001), with better results among women. On average, cross-classification of
      energy and 24 nutrients from the FFQ and means of four FRs placed 39% into
      identical quartiles and 78% into identical and contiguous quartiles, with only 4%
      frankly misclassified. These results suggest that the FFQ is a relatively valid
      instrument for determining usual diet in Quebec adults.

PMID- 15975196
TI  - Food choice motives and the importance of family meals among immigrant mothers.
AB  - To determine the health and social benefits of the family mealtime, we examined
      the contribution of immigrant mothers' food motives to the importance placed on
      family meals, and cultural differences in mothers' food motives and the
      importance ascribed to family meals. Data were taken from a study on food choice
      factors among ten- to 12-year-old children from three cultural communities in
      Montreal. A 24-item, self-administered questionnaire was used to explore food
      choice motives. Each mother was also asked how important it was for her family to
      take the time to eat together, and if the child enjoyed sharing meals with his or
      her family. In all, 209 of the 653 questionnaires distributed were valid; 68 were
      from Haitian, 75 from Portuguese, and 66 from Vietnamese mothers. Five factors
      emerging from factor analyses explained 61.67% of the variance. Analysis of
      variance indicated significant differences between mothers' countries of origin
      for the importance placed on health, pleasure, familiarity, and ingredient
      properties (p<0.005). Among Haitian and Portuguese mothers, health motivations
      emerged as the only significant predictor of the importance given to family
      meals, whereas for Vietnamese mothers, both health and eating familiar foods were
      predictors (p<0.05).

PMID- 15975197
TI  - Psychosocial correlates of nutritional risk in older adults.
AB  - The psychosocial correlates of nutritional risk among older adults were examined
      in a study involving 54 people over age 65 (range, 65 to 98; average, 81), who
      were selected through a convenience sampling strategy. Measures included a
      background questionnaire, Mini Nutritional Assessment, Life Satisfaction Index
      Form Z, Geriatric Depression Scale, and Lubben's Social Network Scale. Seventeen
      percent of participants were found to be at risk of malnutrition. Compared with
      those who had adequate nutrition, at-risk participants had lower levels of social
      support (approaching statistical significance, p=0.08) and life satisfaction (not
      significant), and significantly higher levels of depression (p=0.04).
      Hierarchical multiple regression analysis showed that depression and social
      support were significant correlates of nutritional risk (p=0.01). Nutrition
      professionals should have a multidisciplinary perspective when they assess older
      adults' nutritional status.

PMID- 15975198
TI  - The relevance of selenium to immunity, cancer, and infectious/inflammatory
      diseases.
AB  - Selenium is an essential trace element involved in several key metabolic
      activities via selenoproteins, enzymes that are essential to protect against
      oxidative damage and to regulate immune function. Selenium also may have other
      health benefits unrelated to its enzymatic functions. It may provide important
      health benefits to people whose oxidative stress loads are high, such as those
      with inflammatory or infectious diseases like rheumatoid arthritis or human
      immunodeficiency virus/acquired immunodeficiency syndrome, or who are at high
      risk for cancers, particularly prostate cancer. Some studies have generated
      compelling evidence that selenium is beneficial, either alone or in conjunction
      with other micronutrients. Additional data from large clinical trials that
      provide the highest level of evidence will be key to determining the benefits
      accrued at various selenium intake levels. When the strength of the evidence
      becomes sufficient, clinical health professionals will need to use dietary and
      clinical assessment methods to ensure that people at increased risk for cancer or
      inflammatory and infectious diseases can be appropriately advised about selenium
      intake.

PMID- 15975220
TI  - Abstracts of the Nutrition Society meetings of November 2004, April 2005, June
      2005, and July 2005.

PMID- 15975222
TI  - Analysis of evolution of exon-intron structure of eukaryotic genes.
AB  - The availability of multiple, complete eukaryotic genome sequences allows one to
      address many fundamental evolutionary questions on genome scale. One such
      important, long-standing problem is evolution of exon-intron structure of
      eukaryotic genes. Analysis of orthologous genes from completely sequenced genomes
      revealed numerous shared intron positions in orthologous genes from animals and
      plants and even between animals, plants and protists. The data on shared and
      lineage-specific intron positions were used as the starting point for
      evolutionary reconstruction with parsimony and maximum-likelihood approaches.
      Parsimony methods produce reconstructions with intron-rich ancestors but also
      infer lineage-specific, in many cases, high levels of intron loss and gain.
      Different probabilistic models gave opposite results, apparently depending on
      model parameters and assumptions, from domination of intron loss, with extremely
      intron-rich ancestors, to dramatic excess of gains, to the point of denying any
      true conservation of intron positions among deep eukaryotic lineages. Development
      of models with adequate, realistic parameters and assumptions seems to be crucial
      for obtaining more definitive estimates of intron gain and loss in different
      eukaryotic lineages. Many shared intron positions were detected in ancestral
      eukaryotic paralogues which evolved by duplication prior to the divergence of
      extant eukaryotic lineages. These findings indicate that numerous introns were
      present in eukaryotic genes already at the earliest stages of evolution of
      eukaryotes and are compatible with the hypothesis that the original, catastrophic
      intron invasion accompanied the emergence of the eukaryotic cells. Comparison of
      various features of old and younger introns starts shedding light on probable
      mechanisms of intron insertion, indicating that propagation of old introns is
      unlikely to be a major mechanism for origin of new ones. The existence and
      structure of ancestral protosplice sites were addressed by examining the context
      of introns inserted within codons that encode amino acids conserved in all
      eukaryotes and, accordingly, are not subject to selection for splicing
      efficiency. It was shown that introns indeed predominantly insert into or are
      fixed in specific protosplice sites which have the consensus sequence (A/C)AG|Gt.

PMID- 15975223
TI  - Combining microarrays and genetic analysis.
AB  - Gene expression can be studied at a genome-wide scale with the aid of modern
      microarray technologies. Expression profiling of tens to hundreds of individuals
      in a genetic population can reveal the consequences of genetic variation. In this
      paper it is argued that the design and analysis of such a study is not a matter
      of simply applying the existing and more-or-less standard computational tools for
      microarrays to a new type of experimental data. It is shown how to fully exploit
      the power of genetics through optimal experimental design and analysis for two
      major microarray technologies, cDNA two-colour arrays and Affymetrix short
      oligonucleotide arrays.

PMID- 15975224
TI  - RNAi as a bioinformatics consumer.
AB  - RNAi has shown great potential for use as a tool for biological discovery,
      analysis and therapeutics. The involvement of the RNAi pathway in post
      transcription silencing, transcriptional silencing and epigenetic silencing as
      well as its use as a tool for forward genetics and therapeutics throws up several
      bioinformatics challenges. This paper delineates several areas of research and
      reviews work that has already been done, the tools that are available and the
      challenges that lie ahead.

PMID- 15975225
TI  - Mathematical models of cell cycle regulation.
AB  - The cell division cycle is a fundamental process of cell biology and a detailed
      understanding of its function, regulation and other underlying mechanisms is
      critical to many applications in biotechnology and medicine. Since a
      comprehensive analysis of the molecular mechanisms involved is too complex to be
      performed intuitively, mathematical and computational modelling techniques are
      essential. This paper is a review and analysis of recent approaches attempting to
      model cell cycle regulation by means of protein-protein interaction networks.

PMID- 15975226
TI  - Evolution of web services in bioinformatics.
AB  - Bioinformaticians have developed large collections of tools to make sense of the
      rapidly growing pool of molecular biological data. Biological systems tend to be
      complex and in order to understand them, it is often necessary to link many data
      sets and use more than one tool. Therefore, bioinformaticians have experimented
      with several strategies to try to integrate data sets and tools. Owing to the
      lack of standards for data sets and the interfaces of the tools this is not a
      trivial task. Over the past few years building services with web-based interfaces
      has become a popular way of sharing the data and tools that have resulted from
      many bioinformatics projects. This paper discusses the interoperability problem
      and how web services are being used to try to solve it, resulting in the
      evolution of tools with web interfaces from HTML/web form-based tools not suited
      for automatic workflow generation to a dynamic network of XML-based web services
      that can easily be used to create pipelines.

PMID- 15975227
TI  - VEGA, the genome browser with a difference.
AB  - The Vertebrate Genome Annotation (Vega) database is a community resource for
      browsing manual annotation from a variety of vertebrate genomes of finished
      sequence (http://vega.sanger.ac.uk). Vega is different from other genome browsers
      as it has a standardised classification of genes which encompasses pseudogenes
      and non-coding transcripts. The data is manually curated, which is more accurate
      at identifying splice variants, pseudogenes poly(A) features, non-coding and
      complex gene structures and arrangements than current automated methods. The
      database also contains annotation from regions, not just whole genomes, and
      displays multiple species annotation (human, mouse, dog and zebrafish) for
      comparative analysis. Vega encourages community feedback that results in
      annotation updates and manual annotation of finished vertebrate sequence.

PMID- 15975228
TI  - Biomolecular interaction network database.
AB  - This software review looks at the utility of the Biomolecular Interaction Network
      Database (BIND) as a web database. BIND offers methods common to related biology
      databases and specialisations for its protein interaction data. Searching and
      browsing this database is easy and well integrated with the underlying data and
      the needs of scientists. Interaction networks are visualised with software that
      offers many useful options. The innovative ontoglyphs are used throughout to
      provide visual cues to protein functions, localisation and other aspects one
      needs to know for this data set. One can expect to get useful results that may be
      well integrated with one's research needs.

PMID- 15975230
TI  - HPLC and HPLC-MS analysis of urinary N(epsilon)-monomethyl-lysine.
AB  - Administration of (14)C-labelled L-deprenyl to rats results in the urinary
      elimination of a 14C-labelled compound. The 9-fluorenylmethoxycarbonyl chloride
      reacted urine sample is fractionated by high-performance liquid chromatography
      (HPLC) on an octadecyl silica stationary phase. N(epsilon)-Monomethyl-lysine is
      identified in the fraction containing the majority of the radioactivity.
      Structural elucidation is carried out using HPLC-mass spectrometry in atmospheric
      pressure chemical ionization mode. Identification of the 14C-labelled fragment in
      Ne-monomethyl-lysine is an experimental proof that an N-methylated amino acid is
      generated by transmethylation from a well-known drug. This type of
      transmethylation may have basic importance in the positive side effects of
      certain drugs.

PMID- 15975231
TI  - Preparative SEC column packed with microporous particles prepared from cellulose.
AB  - New microporous particles with large pore size (mean pore diameter of 820 nm) are
      successfully prepared from a mixture of cellulose and konjac glucomannan (RC
      KGM3) in 1.5 M NaOH-0.65 M thiourea aqueous solution by coagulating with 5 weight
      percentage (wt%) CaCl(2), and then 2 wt% HCl aqueous solution. A preparative size
      exclusion chromatographic (SEC) column packed with the gel particles is used for
      the fractionation of a dextran in water. The exclusion limit and fractionation
      range of the stationary phase are molecular masses of 125 yen 104 g/mol and 5.6
      yen 104 to 125 yen 104 g/mol, respectively. The dextran [dextran 50, weight
      average molecular mass (M(w)) = 40.1 yen 104 g/mol, polydispersity index (d) =
      3.5] is fractionated by the preparative SEC column to obtain six fractions, and
      four of them are refractionated twice by the same preparative SEC column. The
      refractionated samples F-3-3 and F-4-3 are characterized by analytical SEC
      combined with laser light scattering and light scattering to obtain M(w) of 91.8
      and 61.9 yen 104 g/mol, as well as d of 1.3 and 1.4, respectively. The results
      indicate that the fractions having narrow molecular mass distribution are
      satisfactorily prepared with the SEC column. The described SEC column can be
      successfully used to fractionate polymers in aqueous solution.

PMID- 15975232
TI  - A modified analytical method for total antioxidant potential assay using RP-HPLC
      with electrochemical detection and its application for pro- and antioxidative
      properties of dopamine measurement.
AB  - Total antioxidant potential (TAP) is usually measured using photometric or
      fluorometric assays. Preliminary results of a reversed-phase high-performance
      liquid chromatography--electrochemical detection assay are given. The method is
      based on the generation of hydroxyl radicals in a Fenton reaction and analysis of
      the product of their interaction with p-hydroxybenzoic acid (3,4-dihydroxybenzoic
      acid). The method is applied to estimate the TAP of dopamine. As a result,
      depending on the concentration, dopamine is pro- or antioxidant. The results are
      compared with TAP measurements using a standard photometric method.

PMID- 15975233
TI  - Determination of nifuratel in human plasma by HPLC and study on its
      pharmacokinetics.
AB  - A simple and sensitive reversed-phase high-performance liquid chromatography
      method using UV detection is established for the determination of nifuratel in
      human plasma and applied to a study of its pharmacokinetics. Plasma samples are
      extracted with ethyl acetate. A C(18) column and a mobile phase of 0.01 M (pH 7)
      phosphate buffer (KH(2)PO(4)) and acetonitrile (61:39, v/v) are used. Analysis is
      run at a flow rate of 1.0 mL/min with the detector operated at a wavelength of
      367 nm. The calibration curve is linear over a concentration range of 0.2-40
      ng/mL with a correlation coefficient of 0.9996. The limit of detection is 0.1
      ng/mL. The mean absolute recovery value is greater than 80%. The intraday
      precision (relative standard deviation) ranges from 1.89% to 7.32%, and the
      interday precision ranges from 1.71% to 7.83%. The results show that the area
      under the plasma concentration-time curve, time to maximum observed plasma
      concentration, maximum concentration reached in the concentration profile, and
      elimination half-life between the testing tablets and reference tablets have no
      significant difference (P > 0.05). Relative bioavailability is 104.0% +/- 16.5%.

PMID- 15975234
TI  - The effect of chromatographic conditions on the separation of selected alkaloids
      in RP-HPTLC.
AB  - Selected alkaloid standards were chromatographed on C18 W layers using various
      aqueous eluents containing an organic modifier and pH 3 buffer to suppress
      silanol ionization or an organic modifier and pH 8 buffer to suppress alkaloid
      ionization. Anionic ion pairs such as sodium dodecyl sulfate, octane-1-sulfonic
      acid sodium salt, pentane-1-sulfonic acid sodium salt, and bis(2-ethylhexyl)ortho
      phosphoric acid are used to improve peak shape, efficiency, and selectivity.
      Amines (e.g., diethylamine, triethylamine, and tetrabutylamonium chloride) are
      incorporated into mobile phases to block surface silanols. The effect of
      chromatographic conditions on the separation of the investigated alkaloids is
      analyzed by the comparison of particular densitograms, asymmetry factor, or
      theoretical plate number. The best efficiency, peak symmetry, and separation
      selectivity of the investigated compounds is obtained through the addition of
      amine (especially diethylamine) to the mobile phases.

PMID- 15975235
TI  - Perchlorate analysis using solid-phase extraction cartridges.
AB  - Perchlorate is a compound of increasing concern as an environmental contaminant
      and is being regulated at increasingly stringent levels. Reliable methods are
      needed to consistently analyze perchlorate at low concentration levels. This
      research investigates the use of solid-phase extraction cartridges as an
      alternative to large-volume injection loops to achieve low-level (microg/L level)
      perchlorate quantitation. The method involves commercially available strong anion
      exchange (SAX) cartridges. Water samples are filtered (100 to 1000 mL) using the
      cartridge, which removes the perchlorate from the solution by anion exchange.
      Then, after the desired volume is filtered, the perchlorate is extracted using 4
      mL of 1% NaOH. In addition, a cleanup method is developed to remove competing
      anions (chloride, sulfate, and carbonate) that are often found in environmental
      samples. Analyses are performed with an ion chromatograph using a 10-microL
      injection loop, yielding a perchlorate method detection limit (MDL) of 210
      microg/L. One-liter volumes of a 2-microg/L perchlorate spiked deionized water
      solution are filtered with SAX SPE. Following extraction and analysis, an MDL of
      0.82 microg/L is obtained, comparable to that found for 1-mL injection loop
      systems (reported as low as 0.53 microg/L). MDL studies are then conducted on
      perchlorate-amended groundwater (solution concentration of 70 microg/L) and
      surface water (solution concentration of 10 microg/L) using a filtration volume
      of 200 mL. The MDLs are 6.7 microg/L for the groundwater and 2.4 microg/L for the
      surface water.

PMID- 15975236
TI  - Determination of prednisolone and prednisone in plasma, whole blood, urine, and
      bound-to-plasma proteins by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic technique for the simultaneous
      determination of prednisolone and prednisone in human plasma, whole blood, urine,
      and bound-to-plasma proteins, using betamethasone as internal standard, is
      presented. Liquid-liquid extraction is used for whole blood samples, and solid
      phase extraction is used for plasma, urine, and proteins bound to plasma. The
      accuracy, precision, specificity, linearity, and repeatability meet the
      requirements of current recommendations in bioanalytical method validation. The
      method is suitable for high altitude pharmacokinetic studies, in which the
      quantitation of drugs in those fluids is required. The results from healthy
      volunteers are presented.

PMID- 15975237
TI  - Development and validation of a HPLC method for 4,7-phenanthroline-5,6-dione I
      and identification of its major impurity by HPLC-MS-APCI.
AB  - In this study, the development and validation of an analytical method for the
      assay of 4,7-phenanthroline-5,6-dione I (dione I) using high-performance liquid
      chromatography (HPLC) and the determination of its synthetic impurities by
      employing the method in HPLC-mass spectrometry with atmospheric-pressure chemical
      ionization and photodiode-array UV detection is reported. The results show that
      dione I is eluted as a spectrally pure peak resolved from its impurities. 5
      Bromo,4-7-phenanthroline is identified as the main impurity. This is supported by
      elemental analysis of the dione I, which demonstrated the presence of bromine.
      Validation parameters such as specificity and selectivity, linearity, accuracy,
      precision, limit of detection (LOD), limit of quantitation (LOQ), ruggedness,
      stability, and system suitability, which are evaluated for this method. The LOD
      and LOQ are 2.0 microg/mL and 50 microg/mL with a 0.50% relative standard
      deviation (%RSD), respectively. The calibration curves showed good linearity over
      the concentration range of 0.05-1.50 mg/mL. The correlation coefficient is >
      0.9991 in each case. The %RSD values for intra- and interday precision studies
      are < 0.40%.

PMID- 15975238
TI  - Simultaneous determination of the binding of amantadine and its analogues to
      synthetic melanin by liquid chromatography after precolumn derivatization with
      dansyl chloride.
AB  - For the determination of amantadine (1-ADA), 2-adamantanamine (2-ADA), memantine
      (MEM), and rimantadine (RIM) in melanin binding studies, the simultaneous
      determination of 1-ADA or 2-ADA, MEM, and RIM is investigated by high-performance
      liquid chromatographic assay with dansyl chloride as a fluorescent derivative
      reagent. Dansyl derivatives with fluorescent intensity are detected at an
      excitation wavelength of 370 nm and an emission wavelength of 506 nm. Retention
      times of 1-ADA, 2-ADA, MEM, and RIM derivatives are 12.2, 12.2, 15.2, and 16.6
      min, respectively. The peak of 1-ADA derivative coelutes with the 2-ADA
      derivative. The limits of detection for 1-ADA, 2-ADA, MEM, and RIM are 0.014,
      0.007, 0.012, and 0.020microM, respectively (signal-to-noise ratio of 3:1). In
      the intra- and interday assay, the range of standard deviation to the average of
      1-ADA, 2-ADA, MEM, and RIM is 4.6-12.7%. Their recovery is also good. The ranking
      order for synthetic melanin binding among these compounds is RIM > MEM > 2-ADA =
      1-ADA. The method is simple, sensitive, and reproducible for simultaneously
      measuring 1-ADA or 2-ADA, MEM, and RIM. Also, it is useful to investigate their
      binding kinetics to melanin.

PMID- 15975239
TI  - Multiplex PCR with multichannel microchip electrophoresis: an ultrafast analysis
      for genetic diseases.
AB  - A Y chromosomal polymorphic markers screening strategy using a multiplex
      polymerase chain reaction (PCR) and DNA microchip electrophoresis technology has
      recently been developed. It is a part of the human Y chromosome haplotyping
      system for studying Japanese population genetics and its relationship with male
      spermatogenic failure. This strategy is based on optimizing and modifying the
      primer set concentrations while keeping all other components of the PCR mixtures
      and conditions similar to those of a singleplex PCR. Well-balanced PCR products
      are obtained without changing even the DNA oligomer melting temperatures. Here, a
      panel of primer sets are used to amplify two groups of Y chromosome markers. The
      first consists of five markers and the second consists of seven markers. Both are
      possibly deleted in infertile men. The microchip electrophoresis technology is
      fast and sensitive, enables direct molecular typing of several Y chromosomal
      markers, and is separated by a difference of as many as six base pairs.

PMID- 15975240
TI  - Size-exclusion chromatographic determination of polymer molar mass averages using
      a fractal calibration.
AB  - The characterization of polymers by size-exclusion chromatography basically
      consists of the determination of the weight-average molar mass (Mw), number
      average molar mass (Mn), and polydispersity index (I). An accurate estimation of
      these magnitudes requires the use of a reliable and trusted calibration curve.
      Three procedures for building up a calibration curve are analyzed in this work.
      The first is the classical universal calibration (UC), based on the elution of
      tetrahydrofuran-polystyrene in a system as reference. The second is based on the
      proper calibration curve made with standards of the sample under study. However,
      two main drawbacks arise when using these methodologies: the nonfulfilment of the
      UC when secondary mechanisms, other than pure size-exclusion, are present in the
      separation process; and the lack of a broad set of narrow standards of the sample
      under analysis in the second procedure. In order to circumvent these
      difficulties, a third, recently-proposed approach based on fractal considerations
      is applied. The accuracy and reliability of this method is proven through the
      calculation of the deviations observed in the estimation of the Mw values for
      polymer samples in different solvent-gel chromatographic systems. Whereas the
      classical UC shows a mean deviation of approximately 80% relative to the values
      given by the manufacturer, the fractal calibration yields a mean deviation of
      approximately 16%, similar to that obtained from the proper calibration.
      Moreover, the fractal procedure only needs one polymeric sample to generate the
      calibration curve.

PMID- 15975241
TI  - Method development for cortisol and cortisone by micellar liquid chromatography
      using sodium dodecyl sulphate: application to urine samples of rugby players.
AB  - The chromatographic behavior of cortisol and cortisone using a micellar medium of
      sodium dodecyl sulphate (SDS) as surfactant, a Hypersil C18 (150- x 3.2-mm i.d.,
      5 microm) column, a flow rate of 0.5 mL/min, and UV absorbance detection at 245
      nm is described. The effect of several organic modifiers and the surfactant
      concentration on the separation is studied. A mobile phase of 18 mM SDS and 8.3%
      tetrahydrofuran allows for the separation of cortisol and cortisone up to
      baseline. These results are also achieved by applying a bivariant optimization
      method. The proposed method is sensitive, reproducible, and selective. In
      addition, it is less expensive than conventional high-performance liquid
      chromatography methods for cortisol and cortisone. The method is applied to the
      determination of cortisol and cortisone in urine samples of rugby players before
      and after stress for doping control purposes.

PMID- 15975242
TI  - Egg-white protein fractionation using new weak anion-exchange resins based on
      poly(glycidyl methacrylate-co-ethylendimethacrylate). Preparation and
      characterization.
AB  - A new formulation for a poly(glycidyl methacrylate-co-ethylendimethacrylate)
      based resin with a 11:9 proportion of monomer to crosslinker is developed and
      amino-functionalized in order to obtain new particulate materials suitable for
      egg-white protein fractionation. Functionalization is carried out using three
      different chemical reagents: diethylamine (DEA), DEA-tetrahydrofuran (THF) (1:1),
      and concentrated ammonia. The ammonia- and DEA-THF-treated polymers are used to
      fractionate egg-white proteins, in particular lysozyme and ovalbumin, by anion
      exchange chromatography in packed column experiments, the latter resin showing
      better performances. Finally, both supports, working at semipreparative scale and
      step-gradient elution, separate pure ovalbumin with a yield of 83%.

PMID- 15975243
TI  - Semipreparative separation and determination of eleutheroside E in Acanthopanax
      giraldii Harms by high-performance liquid chromatography.
AB  - A method for the isolation, purification, and determination of eleutheroside E in
      Acanthopanax giraldii Harms, collected in the Sichuan province (China), is
      established. The water extraction of A. giraldii Harms is pre-isolated using
      macroporous adsorption resin (D-101) and a C18 solid-phase extraction cartridge,
      and the enriched extract is purified to give eleutheroside E (syringaresinol-di-O
      beta-D-glucoside; liriodendrin) by semipreparative reversed-phase high
      performance liquid chromatography. Structure identification is performed by a
      comparison of IR, 1H-NMR, 13C-NMR, and electrospray ionization-mass spectrometric
      data with the literature. The final purity of the compound is 97%. Quantitative
      determination of eleutheroside E in A. giraldii Harms is performed on a Zorbax SB
      C18 (150- x 4.6-mm i.d., 5 microm) column. The linear range of eleutheroside E is
      4.85-194 mg/L (r = 0.9998), and the average recovery is 99.6-101%. The developed
      method is simple, reproducible, and easy to operate. It is useful for the
      evaluation of Acanthopanax giraldii Harms.

PMID- 15975244
TI  - Response factor considerations for the quantitative analysis of western redcedar
      (Thuja plicata) foliar monoterpenes.
AB  - A method is described for quantitative analysis of monoterpenes in western
      redcedar (Thuja plicata) foliage by gas chromatography with flame ionization
      detection. Response factors for monoterpenes identified in redcedar are evaluated
      to determine similarities among monoterpene responses. Evaluation demonstrates
      that redcedar monoterpenes yield detector responses that fall into two groups.
      One monoterpene from each group is used as a standard for quantitative analysis.
      Redcedar monoterpenes are quantitated by comparing analyte response with the
      response factor of one of the standards in single-point calibrations. Homogenized
      foliage samples are extracted with ethyl acetate and the extracts passed through
      a solid phase extraction column of graphitized carbon to remove plant pigments.
      Method bias and repeatability are evaluated by fortifying foliage samples with
      (1S)-(+)-carvone and (1S)-(+)-2-carene and subjecting the samples to the
      extraction and analysis procedures. Detection limits are also assessed from
      fortified samples. Excellent recovery (> 95.0%) and precision (< 5%) are obtained
      from the analysis of 2-carene from fortified samples. Carvone recovery is
      approximately 80% with excellent precision (< 4%). The method limits of detection
      obtained from 2-carene and carvone fortified samples are 4.7 and 13.5 microg/g,
      respectively.

PMID- 15975245
TI  - Simultaneous quantitation of the highly lipophilic atovaquone and hydrophilic
      strong basic proguanil and its metabolites using a new mixed-mode SPE approach
      and steep-gradient LC.
AB  - A bioanalytical method is described for the simultaneous quantitative analysis of
      the highly lipophilic atovaquone and the strong basic proguanil with metabolites
      in plasma. The drugs are extracted from protein precipitated plasma samples on a
      novel mixed-mode solid-phase extraction (SPE) column containing carboxypropyl and
      octyl silica as functional groups. The analytes are further separated and
      quantitated using a steep-gradient liquid chromatographic method on a Zorbax SB
      CN column with UV detection at 245 nm. Two different internal standards (IS) are
      used in the method to compensate for both types of analytes. A structurally
      similar IS to atovaquone is added with acetonitrile to precipitate proteins from
      plasma. A structurally similar IS to proguanil and its metabolites is added with
      phosphate buffer before samples are loaded onto the SPE columns. A single elution
      step is sufficient to elute all analytes. The method is validated according to
      published guidelines and shows excellent performance. The within-day precisions,
      expressed as relative standard deviation, are lower than 5% for all analytes at
      three tested concentrations within the calibration range. The between-day
      precisions are lower than 13% for all analytes at the same tested concentrations.
      The limit of quantitation is 25 nM for the basic substances and 50 nM for
      atovaquone. Several considerations regarding development and optimization of a
      method for determination of analytes with such a difference in physiochemical
      properties are discussed.

PMID- 15975246
TI  - Evaluation of a capillary gas chromatographic impurity test procedure for 4
      hexylaniline.
AB  - A capillary gas chromatographic test procedure for the detection and quantitation
      of impurities in the bulk intermediate, 4-hexylaniline, is evaluated and found to
      be accurate and precise. 4-Hexylaniline is dissolved in methanol and
      chromatographed isothermally at a temperature of 195 degrees C on a 60-m x 0.32
      mm 85% polyethylene glycol-15% dimethylsilicone blend (DX-4) film column. A flame
      ionization detector is used, and the impurities in the parent compound are
      estimated from peak areas on a percent basis compared with the area of the parent
      peak in the chromatogram. Response factors are determined for the known
      impurities. Validation of this test method includes a recovery study of known
      impurity spiked samples fortified in the range of 0.1-1% (w/w). A repeatability
      study is performed, consisting of the analysis of two different synthetic batch
      lots of 4-hexylaniline analyzed over three experimental run days using two
      chromatographic columns of different manufacturing lots. These data and other
      aspects of this test procedure are discussed.

PMID- 15975247
TI  - Simultaneous determination of pantoprazole and its two metabolites in dog plasma
      by HPLC.
AB  - A simple and sensitive high-performance liquid chromatography (HPLC) method is
      developed and validated for simultaneous determination of pantoprazole and its
      two metabolites (pantoprazole sulfone and pantoprazole thioether) in dog plasma
      and applied to a pharmacokinetic study in Beagle dogs. Following a protein
      precipitation procedure, the samples are separated using reversed-phase HPLC
      (C18) by a gradient of acetonitrile and ammonium acetate (pH 6.0) at a flow rate
      of 1.0 mL/min and quantitated using UV detection at 290 nm. Omeprazole is
      selected as the internal standard. The method has a lower limit of quantitation
      of 0.025 microg/mL for pantoprazole and its two metabolites, using 0.1-mL
      aliquots of plasma. The linear calibration curves are obtained in the
      concentration range of 0.025-10.0 microg/mL for three analytes. The intra- and
      interrun precision (relative standard deviation), calculated from quality control
      (QC) samples, is less than 13% for three analytes. The accuracy determined from
      QC samples is between -6.4% and 12%.

PMID- 15975249
TI  - Application of solid-phase microextraction to antidoping analysis: determination
      of stimulants, narcotics, and other classes of substances excreted free in urine.
AB  - This paper describes the application of solid-phase microextraction (SPME) with
      subsequent injection in a gas chromatograph-mass spectrometer (GC-MS) (electron
      impact, full scan) for the screening analysis of stimulants and narcotics in
      urine. Several different kinds of fibers were preliminarily tested and
      comparatively evaluated considering the influence on the overall analytical
      performance of the method; other experimental parameters; and, primarily among
      them, the volume of urine, the pH value, and the time of adsorbtion. The optimal
      experimental conditions have been recorded using 0.5 mL of urine with the pH
      value adjusted to 10 with carbonate buffer, and in which is immersed a
      polydimethylsiloxane/divinylbenzene fiber, with a sampling time of 30 min; the
      fiber is then directly desorbed in the injection port of the GC-MS equipment. All
      the analytes show a good linearity (R2 > 0.99 for most substances) and a good
      reproducibility at the concentration corresponding to the minimum performance
      requirement limit or at the cut-off value fixed by the World AntiDoping Agency
      (CV% < 11). The limit of detection of the method is 50 ng/mL for the majority of
      the substances investigated. Imidazole-based drugs (e.g., naphazoline) and local
      anesthetics can also be included in this screening method. Whenever necessary,
      confirmation analyses may also be performed by following the same pre
      chromatographic procedure. Integrating the SPME process and the GC-MS analysis
      with a dedicated autosampler that combines the microextraction and injection
      capacities maximizes the overall analytical capacity of a single GC-MS system and
      reduces the human labor necessary for and the environmental impact of screening
      for stimulants and narcotics excreted free in urine.

PMID- 15975248
TI  - Determination of hydroxylated polychlorinated biphenyls (HO-PCBs) in blood plasma
      by high-performance liquid chromatography-electrospray ionization-tandem
      quadrupole mass spectrometry.
AB  - Hydroxylated metabolites of polychlorinated biphenyls (HO-PCBs) and
      pentachlorophenol (PCP) are halogenated phenolic compounds, and they are
      increasingly common as environmental contaminants mainly in the blood of wildlife
      and humans. A methodology based on high-performance liquid chromatography
      (reversed-phase)-electrospray (negative) ionization-tandem quadrupole mass
      spectrometry (LC-ESI(-)-MS-MS) in the select ion monitoring or multiple reaction
      monitoring modes was developed for HO-PCB and PCP determination in blood plasma
      and serum. Among 11 environmentally relevant HO-PCB congeners and PCP spiked to
      fetal calf serum, quantitative assessments, including matrix effects on ESI(-)
      suppression/ enhancement, showed process (recovery) efficiencies of 73% to 89%
      without internal standard (IS) correction, and 88% to 103% with IS correction,
      and method limits of quantification ranging from 1 to 50 pg/g (wet weight). Using
      the developed LC-ESI(-)-MS methodology in comparison with GC-MS and GC-ECD based
      approaches, similar results were found for HO-PCB identification and
      quantification in the plasma of polar bear (Ursus maritimus) from the Canadian
      arctic. LC-ESI(-)-MS identified four HO-PCB congeners [4'-HO-2,2',4,6,6'
      pentachlorobiphenyl (4'-HO-CB104), 4-HO-2,3,3',4',5-pentachlorobiphenyl (4-HO
      CB107), 4-HO-2,3,3',5,5',6-hexachlorobiphenyl (4-HO-CB165) and 3'-HO
      2,2',3,4,4',5,5'-heptachlorobiphenyl (3'-HO-CB180)], and 14 additional tetra- to
      hepta-chlorinated HO-PCBs isomers in the polar bear plasma.

PMID- 15975250
TI  - Early-phase postmortem redistribution of the enantiomers of citalopram and its
      demethylated metabolites in rats.
AB  - The aim of this study was to investigate the early-phase postmortem
      redistribution of the enantiomers of citalopram (CIT) and its metabolites
      demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) in a rat model.
      Furthermore, we wanted to examine the role of the lungs as a reservoir of
      postmortem drug release and to investigate the influence of storage temperature
      (21 degrees C vs. 4 degrees C) on postmortem changes. Rats were administered a
      single CIT dose of 100 mg/kg (s.c.), and heart blood and lung samples were
      collected antemortem and 15 min postmortem for enantioselective high-performance
      liquid chromatographic analysis. About three times higher blood drug and
      metabolite levels were observed in the postmortem rats than in the antemortem
      rats (p < 0.0001). Refrigeration at 4 degrees C did not prevent, but
      significantly reduced, the postmortem increase in heart blood CIT levels as
      compared to the concentrations in the rats stored at 21 degrees C (p < 0.05). The
      lung drug concentrations were lower postmortem than antemortem (p < 0.05). The
      enantiomeric (S/R) concentration ratios of CIT and metabolites in blood and lungs
      were of similar magnitude before and after death. The parent-drug-to-metabolite
      ratios for CIT/DCIT were unchanged after death. In conclusion, this study shows
      that heart blood CIT and metabolite levels increase rapidly after death. Further,
      a fall in postmortem CIT concentrations in the lungs was observed, indicating
      that the lungs seemed to represent one major source of drug release during early
      phase postmortem redistribution.

PMID- 15975251
TI  - Determination of ethylene thiourea in urine by HPLC-DAD.
AB  - Ethylene thiourea (ETU) is a metabolite of ethylenebisdithiocarbamates (EBDCs);
      it is the best indicator of exposure to these fungicides. Therefore, high
      performance liquid chromatography with photodiode-array detection (HPLC-DAD) was
      optimized and validated for the determination of ETU in human urines. Urine
      samples were extracted by solid-phase extraction using Extrelut and analyzed
      using HPLC-DAD set at 231 nm. The analyses were carried out using a mobile phase
      of 0.01 M phosphate buffer (pH 4.5) on a C18 Uptisphere NEC-5-20, 250- x 4.6-mm x
      5-microm column. The internal standard used was 4-pyridinecarboxylic acid
      hydrazide. The method was successfully validated in compliance with requirements
      set by the International Committee on Harmonization 1996. The lower limit of
      quantitation was at 1 microg/L, and the linearity was studied from 1 to 100
      microg/L. There were 272 urine samples collected from farmers exposed to EBDCs in
      different regions in France analyzed in this study.

PMID- 15975252
TI  - Application of direct urine LC-MS-MS analysis for screening of novel substances
      in drug abusers.
AB  - A newly developed liquid chromatography-tandem mass spectrometry (LC-MS-MS)
      method was used to study 3000 human urine samples from 3 different populations
      for 23 analytes covering phenylethylamines, benzylpiperazine, and non
      benzodiazepine hypnotics. Direct injection of urine and LC-MS-MS with rapid
      chromatography and atmospheric pressure chemical ionization was used in the
      screening step. The cutoff levels were chosen to be at the limit of detection for
      most analytes to identify as many positive samples as possible. Typically one ion
      transition was monitored from the pseudo-molecular ions in the multiple reaction
      monitoring mode. Of the 797 positive screening findings, 518 (65%) were confirmed
      by a second LC-MS-MS analysis including solid-phase extraction. Confirmed
      analytical findings included 22 cases positive for N-benzylpiperazine, 88 for 3,4
      methylenedioxy-N-methylamphetamine and metabolites, 4 for 1-phenyl-2-butylamine,
      24 for zolpidem and metabolites, 118 for zopiclone and metabolites, and 1 for
      zaleplon. In conclusion, LC-MS-MS was found to be a robust alternative for drugs
      of abuse screening, offering high sensitivity compared with immunochemical
      screening methodology.

PMID- 15975253
TI  - Urinary excretion profiles of two major triazolam metabolites, alpha
      hydroxytriazolam and 4-hydroxytriazolam.
AB  - The objective of this study was to examine urinary excretion profiles of two
      major triazolam metabolites, alpha-hydroxytriazolam (alpha-OHTRZ) and 4
      hydroxytriazolam (4-OHTRZ) in humans. Urine samples were collected from three
      healthy male volunteers who had been previously administered single 0.25- and 0.5
      mg doses of triazolam 24 h and 48 h, respectively, before sample collection.
      After enzymatic hydrolysis and extraction, each sample was analyzed by liquid
      chromatography-mass spectrometry. alpha-OHTRZ was rapidly excreted, with the
      maximum concentrations appearing in the first or second sample collected after
      ingestion, with the majority of the drug being excreted within 12 h. Meanwhile, 4
      OHTRZ was excreted more slowly than alpha-OHTRZ. The alpha-OHTRZ/4-OHTRZ ratios
      were initially greater than 19.7, then decreased rapidly, reaching a nearly
      constant value for times in excess of 12 h.

PMID- 15975254
TI  - Simultaneous determination of buprenorphine and norbuprenorphine in serum by high
      performance liquid chromatography-electrospray ionization-mass spectrometry.
AB  - Buprenorphine is a strong narcotic analgesic. It is also used in the substitution
      therapy for opium alkaloid addicts. The aim of this paper was to develop and
      validate a highly sensitive high-performance liquid chromatography-electrospray
      ionization-mass spectrometry method for simultaneous determination of
      buprenorphine and norbuprenorphine in human serum. The developed methodology was
      then applied to real clinical cases in a clinical toxicology setting. Extraction
      of analytes has been done using solid-phase extraction. Chromatographic
      separation was achieved on a LiChroCART column with a Purospher RP-18e cartridge,
      and for detection an LCQ mass spectrometer with an ion trap analyzer was used.
      Quantitation of buprenorphine and norbuprenorphine was performed in a single ion
      monitoring mode (m/z 468 buprenorphine, m/z 414 for norbuprenorphine) in order to
      increase the sensitivity of the method. The standard curves for both compounds
      were linear over the range of 0.2-10 ng/mL (r2 > 0.995). The quantitation limit
      was 0.2 ng/mL for both analytes. The method was used for quantitation of both
      buprenorphine and norbuprenorphine in the serum of 15 patients undergoing the
      buprenorphine substitution therapy. Serum concentrations ranged between 0.36 and
      4.60 ng/mL for buprenorphine and 0.21 and 2.50 ng/mL for norbuprenorphine, with
      buprenorphine single dosages from 0.8 to 6.0 mg.

PMID- 15975255
TI  - Postmortem distribution of sildenafil in histological material.
AB  - This study reports results of the detection and quantitation of sildenafil
      (Viagra) in biological fluids and tissues and its stability in fixed tissues and
      formalin solutions in which the tissues were fixed. Toxicological analyses were
      performed on samples from a 60-year-old man who died of acute heart failure due
      to myocardiosclerosis. Sildenafil pills were found in his pocket. At the time of
      autopsy, sildenafil was found in body fluids and tissues (blood 0.04 mg/L, bile
      0.99 mg/L, gastric contents 6.84 mg/L, urine 9.60 mg/L, brain 6.43 mg/kg, heart
      6.10 mg/kg, kidney 4.28 mg/kg, liver 5.46 mg/kg, lung 5.38 mg/kg, spleen 1.38
      mg/kg). Tissue samples were preserved in formalin solutions for four weeks.
      Analyses of formalin-fixed tissues and formalin solutions in which the same
      tissues had been preserved allowed the detection and quantitation of sildenafil
      (brain 2.20 mg/kg, formalin from brain 4.01 mg/L; heart 1.46 mg/kg, formalin from
      heart 4.41 mg/L; kidney 0.98 mg/kg, formalin from kidney 3.19 mg/L; liver 2.19
      mg/kg, formalin from liver 3.21 mg/L; lung 1.02 mg/kg, formalin from lung 4.18
      mg/L; spleen 0.28 mg/kg, formalin from spleen 0.94 mg/L). Results indicate that
      sildenafil has good stability in biological specimens subjected to chemical
      fixation.

PMID- 15975256
TI  - An evaluation of selected oral fluid point-of-collection drug-testing devices.
AB  - Point-of-collection oral fluids drug-testing devices are being marketed for a
      variety of medico-legal purposes where they may complement existing technologies
      and be used to detect drugs following recent ingestion. To assess the utility of
      these devices for use in drugged-driving investigations, we performed a
      laboratory evaluation of four devices and those results were published
      previously. In the study reported here, two more devices, Oratect(R) (Branan) and
      Uplink(R) (OraSure), were evaluated for their ability to detect amphetamines,
      cocaine, opiates, and cannabinoids. An additional device, Drugwipe (Securtec),
      was evaluated for the detection of cocaine and cannabinoids. Each of the devices
      was assessed for their ability to meet the manufacturers' claimed cutoff
      concentrations and to meet cutoffs proposed for federal workplace programs. In
      general, the Branan and OraSure devices detected amphetamine, methamphetamine,
      opiates, and cannabinoid metabolite (THC-COOH) well in the concentration ranges
      approximating those proposed by the Substance Abuse and Mental Health Services
      Administration (SAMHSA), but all three devices performed poorly in detecting
      Delta9-tetrahydrocannabinol (THC) at the proposed SAMHSA cutoff. The ability to
      accurately and reliably detect cocaine was dependent on the individual device,
      and the Branan and Securetec devices were more effective than OraSure at
      detecting parent cocaine.

PMID- 15975257
TI  - Quantitative GC-MS analysis of D(9)-tetrahydrocannabinol in fiber hemp varieties.
AB  - A sensitive and specific method for the determination of total available D(9)
      tetrahydrocannabinol in fiber hemp varieties is described. The method was used
      for the regulatory purposes in which the detection of higher than the maximum
      allowed concentration of the psychoactive cannabinoid, D(9)-tetrahydrocannabinol,
      in industrial fiber hemp would result in cancellation of the grower's license.
      Cannabinoids were extracted from dry leaf powder into hexane containing internal
      standard chrysene-d(12) using sonication. D(9)-Tetrahydrocannabinol in the
      extract was separated by gas chromatography and quantitated by mass spectroscopy.
      A linear calibration range extending to 40 ppm and a limit of detection of 0.2 ng
      were obtained by using the total ion current mode of detection.

PMID- 15975258
TI  - Investigation of a fatality due to trazodone poisoning: case report and
      literature review.
AB  - Trazodone is an antidepressant agent used in Spain since 1975. There are few
      documented reports of fatalities solely attributed to trazodone and none in which
      the main metabolite is analyzed. A fatal case of self-poisoning following oral
      ingestion is reported along with a description of the validated analytical
      methods involved, a discussion of poisoning characteristics, and a review of
      reports describing trazodone overdose cases with analytical results. The deceased
      was an 86-year-old man with cancer, who suffered depression. He went to see his
      doctor in a primary health care unit and told him he had just taken an unknown
      amount of tablets of Deprax to commit suicide. The doctor induced emesis as a
      first emergency measure. His death occurred before arriving to the hospital, and
      he left a suicide note nearby. Systematic toxicological analysis of postmortem
      blood used routinely in our laboratory revealed the presence of trazodone 4.9
      mg/L and m-chlorophenyl-piperazine (m-CPP) 0.6 mg/L, its active and major
      metabolite. In addition, metamizol 19.6 mg/L and 4-methyl-amino-antipyrine (4
      MAA) 40.7 mg/L, its active metabolite, were also found in blood. All drugs and
      metabolites involved in the case were detected using gas chromatography-nitrogen
      phosphorus detection (GC-NPD) and confirmed using gas chromatography-mass
      spectrometry (GC-MS) mode total ion chromatogram. An additional high-performance
      liquid chromatography-diode array detection (HPLC-DAD) screening also obtained
      the same results. Quantitation of trazodone together with its metabolite in blood
      was carried out using GC-NPD, while quantitation of metamizol was performed using
      HPLC-DAD. Limits of detection for trazodone and m-CPP were 33 and 11 microg/L,
      respectively, absolute recoveries were more than 86% and 75%, respectively, intra
      assay precisions less than 4%, interassay precisions less than 5%, and linearity
      up to 2.0 mg/L. Limit of detection for metamizol was 1117 microg/L, absolute
      recovery more than 84%, intra-assay precision less than 8%, interassay precision
      less than 12%, and linearity up to 48 mg/L. Based on the autopsy findings,
      patient history, toxicology results, and previously reported trazodone
      intoxications, the forensic pathologists ruled that the cause of death was due to
      an overdose of trazodone, and the manner of death was listed as suicide.

PMID- 15975260
TI  - Characterisation of protein microheterogeneity and protein complexes using on
      chip immunoaffinity purification-mass spectrometry.
AB  - Post-translational modification of proteins may influence their interactions with
      other plasma proteins, as well as having an effect on many aspects of the
      metabolism of the protein, such as receptor binding, tissue uptake, degradation
      and excretion. Many post-translational modifications occur in a physiological
      context, while others are specific for certain diseases, which is why they are of
      diagnostic importance in clinical proteomics. Analytical approaches to the study
      of post-translational modifications and protein complexes through the combined
      use of on-chip immunological affinity purification on a surface-enhanced laser
      desorption/ionisation platform and subsequent mass spectrometry are illustrated
      in the author's own work relating to plasma transthyretin (TTR) and retinol
      binding protein (RBP). In those studies, both the aspects of post-translational
      modifications of TTR and the formation of a protein complex between TTR and RBP
      have been discussed. Such aspects are of diagnostic interest in clinical
      proteomics, especially with regard to the modification of TTR in relation to the
      occurrence of amyloidotic diseases.

PMID- 15975261
TI  - Advances in clinical cancer proteomics: SELDI-ToF-mass spectrometry and biomarker
      discovery.
AB  - For most cancers, survival rates depend on the early detection of the disease. So
      far, no biomarkers exist to cope with this difficult task. New proteomic
      technologies have brought the hope of discovering novel early cancer-specific
      biomarkers in complex biological samples and/or of the setting up of new
      clinically relevant test systems. Novel mass spectrometry-(MS) based technologies
      in particular, such as surface-enhanced laser desorption/ionisation time of
      flight (SELDI-ToF-MS), have shown promising results in the recent literature.
      Here, proteomic profiles of control and disease states are compared to find
      biomarkers for diagnosis. This paper aims to address the authors' own work and
      that of other groups in clinical cancer proteomics based on SELDI-ToF-MS.
      Shortcomings and hopes for the future are discussed.

PMID- 15975262
TI  - Mass spectrometry-based quantitative proteomic profiling.
AB  - Quantitative proteomics involves the identification and quantitation of protein
      components in various biological systems. Stable isotope labelling technology, by
      both metabolic and chemical methods, has been the most commonly used approach for
      global proteome-wide profiling. Recently, its capability has been extended from
      labelled pairs to multiple labels, allowing for the simultaneous quantification
      of multiplex samples. The ion intensity-based quantitative approach has
      progressively gained more popularity as mass spectrometry performance has
      improved significantly. Although some success has been reported, it remains
      difficult comprehensively to characterise the global proteome, due to its
      enormous complexity and dynamic range. The use of sub-proteome fractionation
      techniques permits a simplification of the proteome and provides a practical step
      towards the ultimate dissection of the entire proteome. Further development of
      the technology for targeting sub-proteomes on a functional basis - such as
      selecting proteins with differential expression profiles from mass spectrometric
      analyses, for further mass spectrometric sequencing in an intelligent manner--is
      expected in the near future.

PMID- 15975263
TI  - SPR-MS in functional proteomics.
AB  - The mapping of protein networks and the establishment of the functional
      relationships between expressed proteins and their effects on cellular processes
      represents a great challenge for functional or interaction proteomics. The
      combination of surface plasmon resonance (SPR)-based technology with mass
      spectrometry (MS) has created a unique analytical tool for functional proteomics
      investigations. Proteins are affinity purified, quantified and characterised in
      terms of their interactions, while the mass spectrometer identifies and
      structurally characterises the biomolecules. Recent developments have led to a
      closer integration of these key technologies, providing a combined approach which
      enables identification of proteins selected on the basis of their functional
      binding criteria. In addition to a historical overview of this field, some recent
      detailed examples of combined SPR-MS approaches will be reviewed in a number of
      key application areas, including ligand fishing, peptide sequence and post
      translational modification analysis by SPR-MS/MS and enzyme inhibitor screening.

PMID- 15975264
TI  - Moss (Physcomitrella patens) functional genomics--Gene discovery and tool
      development, with implications for crop plants and human health.
AB  - Recently, the moss Physcomitrella patens was established as a versatile tool in
      plant functional genomics. Mosses represent the oldest living clade of land
      plants, separated by approximately 450 million years of evolution from crop
      plants. Consequently, mosses contain metabolites and genes not known from these
      seed plants. In Physcomitrella, nuclear genes can be targeted by homologous
      recombination as efficiently as in yeast, allowing reverse genetics approaches in
      plants at high-throughput levels for the first time. Comprehensive expressed
      sequence tag databases gave new insights into the levels of diversity in land
      plants which are now ready to be exploited in plant biotechnology. In forward
      genetics screens, saturated tagged mutant collections help to unravel novel gene 
      function relationships. Additionally, proteomics tools are at hand to analyse
      subcellular proteomes, as well as the phosphoproteome, as the core of eukaryotic
      signal transduction. Moreover, specifically designed Physcomitrella strains can
      produce human therapeutic proteins safely and cost-effectively in bioreactors.

PMID- 15975265
TI  - Strategies for characterising cis-regulatory elements in Xenopus.
AB  - Understanding the cis-regulatory architecture of metazoan organisms is the
      greatest challenge facing genome biology today. In vertebrate organisms, distinct
      sequence elements mediate transcriptional regulation and are scattered throughout
      the genome, either proximal or distal to promoters. The identification of
      transcriptional enhancers has proven rather difficult by conventional
      experimental approaches. In the past decade, the rapid generation of genomic
      sequences for multiple vertebrate organisms, accompanied by sophisticated
      comparative tools, has facilitated the identification of non-coding
      evolutionarily conserved regions that may encode cis-regulatory elements.
      Validating computational predictions and characterising cis-regulatory elements
      in vivo, however, has been a major bottleneck, mainly because the most commonly
      used organism for these experiments has been the mouse, and generating transgenic
      mice or modifying the mouse genome continues to be a labour-intensive, low
      throughput, expensive process. This has led to the use of Xenopus, which holds
      great promise for high-throughput interrogation of putative cis-regulatory
      elements. In particular, Xenopus tropicalis may become particularly powerful for
      elucidating regulatory networks, chiefly because it is amenable to genetic
      manipulations, and its genome is being sequenced.

PMID- 15975266
TI  - Proteomics approaches to biomarker detection.
AB  - The development of mass spectrometry (MS) technologies has brought the ability to
      gather massive amounts of data characterising the proteomes of complex mixtures.
      A major focus in proteomics is to leverage this data-gathering capability to
      conduct comparative analyses of biofluids from healthy and disease-affected
      patients for the identification of highly specific biomarkers and/or the
      development of MS-based diagnostic platforms. Much effort has gone into
      optimising the biofluid proteome coverage that can be obtained using these
      technologies, leaving proteomics poised to make an important impact in disease
      diagnostics in the future.

PMID- 15975267
TI  - Solution phase isoelectric fractionation in the multi-compartment electrolyser: a
      divide and conquer strategy for the analysis of complex proteomes.
AB  - Sample complexity frequently interferes with the analysis of low-abundance
      proteins by two-dimensional gel electrophoresis (2DGE). Ideally, high abundance
      proteins should be removed, allowing low-abundance proteins to be applied at much
      higher concentrations than is possible with the unfractionated sample. One
      approach is to partition the sample in a manner that segregates the bulk of
      extraneous proteins from the protein(s) of interest. Solution phase isoelectric
      focusing in the multi-compartment electrolyser generates fractions of discrete
      isoelectric point (pI) intervals allowing isolated narrow segments of a proteome
      to be analysed individually by 2DGE. It is particularly useful for the isolation
      of low-abundance proteins of extremely basic or acidic pI.

PMID- 15975268
TI  - [Further systematize and standardize the diagnosis and treatment of liver
      cirrhosis].

PMID- 15975269
TI  - [Use of direct portal vein puncture portography with modified TIPS treatment in
      patients with portal hypertension and gastro-esophageal varices bleeding].
AB  - OBJECTIVE: To explore a better procedure for transjugular intrahepatic
      portosystemic shunt (TIPS) in order to improve its safety and to extend its
      indications. METHODS: To puncture the right portal branch under sonographic
      guidance in 20 patients with portal hypertension and gastro-esophageal bleeding.
      The Teflon sheath with gold marker was put into the portal vein; anterior and
      lateral portography was made, portal pressure was measured and the gastric
      coronal vein was embolized. The gold marker was put into the portal vein puncture
      site and the Rups-100 was guided under the gold marker during the TIPS puncture
      procedure. Anterior and lateral portography was again made to make sure the
      puncture site was 2 cm away from the portal vein bifurcation. In some cases a 10F
      sheath was used to suck the thrombosis in the portal vein, and a balloon was used
      to dilate the parenchyma channel and then a stent was released smoothly. RESULTS:
      20 reformed TIPS were successfully performed on all patients and their gastric
      esophageal bleedings were controlled immediately. 37 punctures were made in 20 of
      those cases; the average puncture per patient was 1.85+/-0.67, lower than that of
      the traditional method. The pressure of the portal vein declined from (30.5+/
      1.1) mmHg to (16.9+/-0.9) mmHg, P < 0.05, showing that the difference of portal
      vein pressure before and after the reformed TIPS was significant. 25 stents were
      placed, and no complications occurred during the procedure in any of the cases.
      CONCLUSION: Direct portal vein puncture portography and gold marker guided TIPS
      procedure is feasible and safe; the indications of TIPS could be further
      extended.

PMID- 15975270
TI  - [Analysis of prognosis of patients with decompensated liver cirrhosis using the
      criterion of the Model of End-Stage Liver Disease].
AB  - OBJECTIVE: To investigate the relationship between the Model for End-Stage Liver
      Disease (MELD) with Child-Pugh scoring, and the prognosis of patients with
      decompensated liver cirrhosis. METHODS: 110 patients with decompensated liver
      cirrhosis were graded with MELD formula and with Child-Pugh. The death rate was
      observed within three months. RESULTS: 31 patients died within 3-months. The
      mortality of patients whose MELD scores were between 10 approximately 19, 20
      approximately 29, and > or = 30 was higher than those with MELD < or = 9 (The
      mortality of those with MELD less than 9, 10 approximately 19, 20 approximately
      29, or > or = 30 was 11.76%, 38.18%, 64.71%, 75.00% respectively). The mortality
      of patients whose MELD scores were > or = 18 was higher than those with MELD < 18
      (The mortality of those with MELD < 18, MELD > or = 18 was 26.58%, 58.06%
      respectively. chi2 = 9.643). The mortality of Child A, B, C was 14.89%, 42.55%,
      75% respectively. CONCLUSION: Both MELD and Child-Pugh scores can accurately
      predict the short-term prognosis of patients with decompensated liver cirrhosis.

PMID- 15975271
TI  - [Analysis of HLA alleles polymorphism in Chinese patients with primary biliary
      cirrhosis].
AB  - OBJECTIVE: To investigate the frequencies of human leuckocyte antigens (HLA) -A,
      B and DRB1 alleles in Chinese patients with primary biliary cirrhosis (PBC) using
      polymerase chain reaction-based techniques, and to assess the correlation of HLA
      molecules with other clinical and laboratory profiles. METHODS: Genotyping of HLA
      A, B, and DRB1 were performed in 65 well-characterized patients with primary
      biliary cirrhosis and 431 healthy controls with PCR amplification with sequence
      specific primers (PCR-SSP). RESULTS: The frequency of DRB1*0701 was increased to
      29.2% compared with 13.9% in the controls (PC < 0.05, OR = 2.55, 95% CI: 1.4
      approximately 4.6). No association was found with HLA-DRB1*08 which had been
      constantly reported. The A*2 allele (53.8%) was more frequent in the PBC patient
      group but without a significant statistical difference. The frequencies for the
      other A, B and DRB1 alleles were similar between patients and healthy controls.
      There was no difference between patients with or without DRB1*0701 in some
      clinical and laboratory profiles. CONCLUSION: Susceptibility to primary biliary
      cirrhosis in Chinese is associated with DRB1*0701 allele and differs from people
      in North America, South America, North Europe and even in Japan, but the
      association is not restricted to any particular subgroup of patients. Valine at
      position 78 of HLA DRbeta1 may play an important role in the pathogenesis of
      primary biliary cirrhosis.

PMID- 15975272
TI  - [Relationship between the quantities of peripheral dendritic cells and of serum
      HBV DNA and the inflammatory reaction levels in the liver].
AB  - OBJECTIVES: To investigate the relationship between the quantity of peripheral
      dendritic cell (DC) and of serum HBV DNA and the inflammatory level in chronic
      hepatitis B (CHB). METHODS: The myeloid DC (DC1) and plasmacytoid DC (DC2) in
      fresh peripheral blood were enumerated by using three-color flow cytometry in
      chronic hepatitis B patients and healthy donors. The hepatic inflammatory levels
      were evaluated by percutaneous liver biopsy. The serum HBV DNA levels were
      determined by real-time PCR. RESULTS: CHB patients with serum HBV DNA < or =
      10(6) copies/ml exhibited a significant increase in the percentage of circulating
      DC2 in comparison with those of CHB patients with serum HBV DNA > or = 10(6) and
      with healthy donors (P < 0.05). The two latter groups showed no significant
      differences between each other. There was also no significant difference in the
      relative quantity of peripheral blood DC1 among the three groups mentioned above
      (P = 0.162). No evidence was found to support that the relative quantity of
      peripheral blood DC2 was associated with the clinical severity of the disease or
      the inflammatory level in the liver (P > 0.05). CONCLUSION: The relative quantity
      of peripheral blood DC2 is associated with HBV DNA level. It is suggested that
      DC2 may play a pivotal role in inhibiting HBV replication in CHB patients. There
      was no relationship found between relative quantities of DCs and the inflammatory
      level in the liver.

PMID- 15975273
TI  - [Study of phenotypes and functions of cord blood dendritic cells from fetuses
      whose mothers had chronic hepatitis B].
AB  - OBJECTIVE: To investigate the phenotypes and functions of cord blood dendritic
      cells of fetuses whose mothers are patients with chronic hepatitis B. METHODS:
      Peripheral blood and cord blood mononuclear cells (PBMC) were isolated from whole
      blood by density gradient centrifugation with Ficoll-Hypaque. The adherent cells
      were cultured in AIM-V medium containing recombinant human IL-4, TNF-alpha and GM
      CSF. On day 9, mature DCs (mDC) were harvested and used for phenotype analysis.
      The amounts of IL-12 which dendritic cells produced were measured. The dendritic
      cells that were studied and compared were from cord blood of fetuses of both CHB
      positive and negative mothers and from CHC adult peripheral blood. RESULTS: The
      expression rate of CD80 and CD83 of chronic hepatitis B mother cord blood
      dendritic cells was low compared with that of the healthy cord blood, healthy
      adult peripheral blood, and chronic hepatitis B adult peripheral blood, P < 0.05.
      The amount of IL-12 produced by chronic hepatitis B mother cord blood dendritic
      cells was lower than that of healthy cord blood, healthy adult peripheral blood,
      chronic hepatitis B adult peripheral blood (P < 0.05). The T lymphocyte
      proliferation inducing ability of dendritic cells of healthy adult peripheral
      blood was higher in inducing cord blood T lymphocytes proliferation, which was
      greater than that of the healthy adult peripheral blood in inducing adult T
      lymphocytes and was greater than that of the healthy cord blood dendritic cells
      in inducing cord blood T lymphocytes, which was greater than that of the healthy
      cord blood in inducing adult T lymphocytes, which was greater than that of
      chronic hepatitis B mothers in inducing cord blood T lymphocytes, which was
      greater than that of chronic hepatitis B mother cord blood in inducing adult T
      lymphocytes. CONCLUSION: The maturation and functioning of CHB mother cord blood
      dendritic cells were lower than those of healthy cord blood, healthy adult
      peripheral blood and CHB adult peripheral blood.

PMID- 15975274
TI  - [Influence of wen-yang herbs on hemodynamics in liver fibrotic rats].
AB  - OBJECTIVES: To observe the influence of wen-yang herbs on the hemodynamics in
      liver fibrotic rats. METHODS: Wistar rats with liver fibrosis, induced by carbon
      tetrachloride and alcohol, were randomly divided into a treatment group and a
      control group. The treatment group was administered wen-yang herbs and the
      control group saline. At the end of the experiment, the hemodynamic markers of
      the liver and the mesentery, the liver function and hydroxyproline content of
      liver tissues between the two groups were compared. Blood volume of the livers
      and hydroxyproline content of liver tissues were also determined. RESULTS: Blood
      volume of the liver and mesentery (P < 0.01) and blood flow velocity of small
      vein of mesentery (P < 0.05) of the treatment group were distinctly higher than
      the control group. The hydroxyproline content (P < 0.01) of the treatment group
      was remarkably reduced and liver function was improved. CONCLUSION: Wen-yang
      herbs can activate microcirculation of the liver and mesentery, decrease the
      deposit of collagen in the liver and improve liver function.

PMID- 15975275
TI  - [An in vivo study on interlukin-10 inhibiting the expression and secretion of
      collagen I and IV in hepatic stellate cells].
AB  - OBJECTIVES: To investigate the effect of interlukin-10 (IL-10) on expression and
      secretion of collagen I, IV in rat's hepatic stellate cells (HSC) of livers
      injured by CCl4. METHOD: The adenovirus vector encoded IL-10 gene was used to
      transfect rats with liver injury via the caudal veins. HSC were isolated and
      purified from the rat livers by collagenase IV perfusion and density gradient
      centrifugation with Nycodenz. The expression of collagen I, IV mRNA in HSC was
      detected by semi-quantitative RT-PCR method and the secretion of collagen I, IV
      in culture serum of HSC by ELISA method. The quantity of collagen was measured in
      the van Gieson stained histological liver preparations. RESULTS: The expression
      and secretion of collagen I, IV in the adenovirus vector encoding IL-10 gene
      group were significantly lower than those in the adenovirus vector without IL-10
      gene group and the control group (P < 0.05). The quantity of collagen in the
      treatment group was lower than that in the control group. CONCLUSION: IL-10 can
      inhibit collagen I, IV expression and secretion in rat HSC.

PMID- 15975276
TI  - [Relationship between DLC-1 expressions and metastasis in hepatocellular
      carcinoma].
AB  - OBJECTIVES: To study the relationship between the expression level of DLC-1 mRNA
      (located in 8p) and the invasion/metastasis of human hepatocellular carcinoma
      (HCC). METHODS: Fifty-one surgical specimens of human HCC were divided into high
      invasive and low invasive groups according to their clinicopathological features.
      DLC-1 mRNA expression was studied in the 51 HCC specimens as well as 5 different
      metastasis potential cell lines using real-time quantitative PCR (RQ-PCR).
      RESULTS: The expression level of DLC-1 mRNA in HCC specimens with high
      invasiveness was significantly lower than that with low invasiveness (P < 0.05).
      The expression levels of DLC-1 mRNA were significantly different between non
      metastatic (Hep3B and HepG2) and metastatic (MHCC97-H, MHCC97-L and HCCLM3) cell
      lines (P < 0.05). From MHCC97-L to HCCLM3, with an increase of invasiveness and
      metastatic potentials, the expression level of DLC-1 decreased correspondingly,
      and its expression level in HCCLM3 was significantly lower than that in MHCC97-L
      (P < 0.01). CONCLUSION: The expression of DLC-1 mRNA may play an important role
      in inhibiting the invasiveness and metastasis of HCC.

PMID- 15975277
TI  - [Clinical effects of dendritic cells pulsed with autologous hepatoma cell lysates
      on the postoperative recurrence and metastasis of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate clinical effects of dendritic cells (DCs) pulsed with
      autologous hepatoma cell lysates on postoperative recurrence and metastasis of
      hepatocellular carcinoma (HCC). METHODS: DCs isolated from peripheral blood
      mononuclear cells of HCC patients were cultured and propagated in vitro using
      rhGM-CSF and rhIL-4, and then were pulsed with autologous hepatoma cell lysates.
      Thirty postoperative patients with HCC were randomly divided into two groups.
      Fifteen cases were treated with DC vaccine; fifteen cases received chemotherapy
      only as a control group. Immune function, clinical effects, hepatic tumor
      recurrence rate and the survival rate of patients of the two groups were observed
      and compared. RESULTS: The levels of CD3+, CD4+/CD8+ and NK cells in the DC
      vaccine group were significantly increased after vaccination, while those of the
      control group had no significant changes. The concentration of IL-10 in the DC
      vaccine group was significantly decreased after the vaccination (P < 0.05). The
      hepatic tumor recurrence rate at 18 months in the DC vaccine group was 13.33%,
      compared with 53.33% in the control group (P < 0.05). The survival rate in the
      former was 93.33%, compared with that of 60% in the later (P < 0.05). CONCLUSION:
      Hepatoma cell lysates pulsed DC vaccine may improve the immune function of the
      postoperative HCC patients and play an important role in prevention of
      postoperative recurrence and metastasis of HCC, which would provide an innovative
      approach for the immunotherapy of HCC.

PMID- 15975278
TI  - [Differential analysis of tyrosine-phosphorylated proteins in human
      hepatocellular carcinoma cell lines with different metastasis potentials].
AB  - OBJECTIVES: To compare expressions of tyrosine-phosphorylated proteins in
      different hepatocellular carcinoma cell lines with different metastasis potential
      and to screen key molecules associated with HCC metastasis and recurrence.
      METHODS: Using two-dimensional electrophoresis, Western blotting and MALDI-TOF
      MS/MS, we analyzed tyrosine-phosphorylated protein profiles of Hep3B, MHCC97L and
      MHCC97H, HCC cell lines with different metastasis potentials. RESULTS: 10 spots
      were detected in Hep3B, 19 in MHCC97L and 17 in MHCC97H. Seventeen significantly
      different phosphotyrosine proteins in gel were identified by MALDI-TOF-MS/MS,
      including Annexin I. CONCLUSION: The changed expression of tyrosine
      phosphorylated proteins is associated with HCC metastasis and recurrence.

PMID- 15975279
TI  - [Detection and comparison of transcriptional activities of tumor-specific
      survivin and alpha-fetoprotein promoters in human hepatocellular carcinoma
      cells].
AB  - OBJECTIVE: To detect and compare the transcriptional activities of tumor-specific
      survivin and AFP promoters in various hepatocellular carcinoma cell lines and to
      lay some groundwork for targeting gene therapy in human hepatocellular carcinoma.
      METHODS: The fragment of survivin and AFP promoters were acquired by PCR
      amplification and were cloned into the reporter plasmid pGL3-Basic, which
      contained a luciferase gene. The constructed eukaryotic expression plasmid pGL3
      SUR and pGL3-AFP, in which the expression of the luciferase was derived by
      survivin or the AFP promoter, were transfected into three HCC cell lines. At 24
      hours post transfection (p.t.), the activity of the luciferase was determined
      with Dual-Luciferase Reporter Assay System. A pGL3-CMV, containing the CMV
      promoter controlled luciferase gene, was used as a positive control. RESULTS:
      Both survivin and AFP promoters had transcriptional activities in all three HCC
      cell lines and the transcriptional activity of the survivin promoter was much
      higher than the AFP promoter (52-98 times) and reached a level of 16%
      approximately 21% of the transcriptional activity of the CMV promoter.
      CONCLUSION: Our data reveals that the survivin promoter possesses a high
      transcriptional activity in all three established HCC cell lines and may serve as
      a useful tool for transcriptional targeting gene therapy of HCCs.

PMID- 15975280
TI  - [Influence of reconstruction of immunological functions of T lymphocytes on mouse
      hepatocarcinoma metastasis].
AB  - OBJECTIVE: To investigate the effectiveness of reconstruction of immunological
      functions of T cells on the degree of metastases of mouse hepatocarcinoma and the
      mechanisms of their functioning. METHODS: The T cell model of immunological
      functions in Balb/c nu/nu mice was established and the effectiveness of the model
      was evaluated. The mice were divided into 4 groups. The immunological functions
      of T cells in experiment groups of Balb/c nu/nu mice were reconstructed.
      Metastases of the cancer in lymph nodes in each group were examined
      histologically. The formation time and growth rate of the tumors were calculated.
      The expression of MHCI and II of the tumor cell line and the difference of
      expression of immune associated gene were detected by Th1-Th2-Th3 gene array.
      RESULTS: The ratio of CD3, CD4, CD8 and CD4/CD8 in the reconstructed group was
      higher than that in the control group. The average formation time was 7.7+/-0.6
      days in Balb/c nu/nu mice and 11.5+/-1.3 days in Balb/c mice. The extent of
      metastases of the experiment group was lower than that of the control group (P <
      0.05). The expression of MHCI of the high metastasis cell line was lower than
      that of the low metastasis cell line (P < 0.05). The expressions of Th1/Th2
      associated genes in lymphocytes of high metastasis mice were lower than those of
      the low metastasis mice. CONCLUSION: Reconstruction of the immunological function
      of T cells can influence the metastasis of mouse hepatocarcinoma. The alteration
      of MHC molecule and low expression of Th1/Th2 correlated genes in lymphocytes may
      be a factor influencing the metastasis of liver cancer.

PMID- 15975281
TI  - [Activation of Kupffer cell TLR2 signaling pathway during hepatic
      ischemia/reperfusion injury process in mice and it's significance].
AB  - OBJECTIVE: To study changes of TLR2 signaling pathway expression in Kupffer cells
      during the process of hepatic ischemia/reperfusion in a mice model and the
      mechanism of TLR2 signaling pathway participating in hepatic ischemia/reperfusion
      injury. METHODS: BALB/c mice were divided into 3 groups: sham operation (SH),
      ischemia/reperfusion (I/R) and GdCl3 treatment (Gd) groups. After 4 h of
      reperfusion, the expression of TLR2 mRNA and membrane TLR2 protein were analyzed
      in ischemic lobes of the livers, and in Kupffer cells isolated from ischemic
      lobes. The expression of NF-kappaB in ischemic lobes was also examined. Levels of
      endotoxin, ALT and TNFalpha were measured at the same time point. RESULTS: The
      expressions of TLR2 mRNA and protein in both ischemic hepatic lobes and Kupffer
      cells isolated from ischemic lobes were increased in the I/R group compared to
      those in the SH group, as well as the expression of NF-kappaB in ischemic lobes,
      which was down regulated by intravenous GdCl3 treatment. Levels of ALT and
      TNFalpha in the portal vein were higher in the I/R group than in the SH group,
      which also were decreased with treatment of GdCl3. The level of endotoxin in the
      three groups remained constant. CONCLUSION: TLR2 signaling pathway in Kupffer
      cells is activated during the process of hepatic ischemic/reperfusion injury. The
      activation of TLR2 signaling pathway in Kupffer cells may play a role in this
      process.

PMID- 15975282
TI  - [Effects of insulin treatment on intracellular lipid content in livers and
      insulin resistance in type 2 diabetic rats].
AB  - OBJECTIVE: To study effects of insulin treatment on intracellular lipid content
      in livers and insulin resistance of type 2 diabetic rats. METHODS: Type 2
      diabetic rats were induced by injecting streptozotocin (25 mg/kg) and fat rich
      food. Then according to the results of the oral glucose tolerance test (OGTT) and
      glucose-induced insulin secretion test (IST), the rats were divided into two
      groups: control group (DC) and insulin treated group (DI). Normal rats (NC)
      served as controls. The treatment of each group with either NPH insulin (4
      approximately 6 U . kg-1. d-1), or saline continued for 4 weeks. Body weight,
      OGTT, IST, blood lipids, intracellular lipids in liver and liver histology were
      studied. The insulin sensitivity index (ISI) was applied to assess the status of
      insulin resistance. RESULTS: Blood lipid and intracellular lipids in livers in
      the DC were higher than those in NC (t = 2.59 approximately 15.77, P < 0.05) and
      the ISI was lower (t = 3.16, P < 0.05), with many fatty droplets appearing in the
      livers. In comparison to DC, DI showed that blood lipids were decreased, but
      lipids in livers were markedly increased (TG, TC, FFA increased 55.7%, 19.87%,
      22.2%, respectively), and fatty droplets in hepatocytes were larger, but the ISI
      did not change significantly. CONCLUSION: Insulin treatment can make blood
      glucose normal, increase the intracellular lipid content in the liver, and not
      increase the insulin resistance significantly.

PMID- 15975283
TI  - [YVDD is the primary symbol of gene mutation in hepatitis B patients treated with
      lamivudine].

PMID- 15975284
TI  - [Therapeutic strategies for liver cirrhosis with bleeding from esophageal
      varices].

PMID- 15975285
TI  - [Treatment of hepatorenal syndrome in liver cirrhosis].

PMID- 15975286
TI  - [Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis].

PMID- 15975287
TI  - [Effects of strengthening and regulating spleen-qi recipe on nude mice with
      metastatic human hepatocellular carcinoma].

PMID- 15975288
TI  - [An experimental study on the effect of naloxone on alcoholic fatty livers].

PMID- 15975289
TI  - [Effect of Cordyceps sinensis on rats with nonalcoholic fatty livers].

PMID- 15975290
TI  - [Real time monitoring of heparin anticoagulant therapy in severe hepatitis
      patients treated with plasma exchange].

PMID- 15975291
TI  - [Study of Newcastle disease virus killing hepatocellular carcinoma cells in
      vitro].

PMID- 15975292
TI  - [L-[1-13C] phenylalanie breath test as a quantitative liver function assessment-
      a study on rats].

PMID- 15975293
TI  - [Effects of ethanol on HBV replication and gene expression in HBV transgenic
      mice].

PMID- 15975294
TI  - [Analysis of antibiotic resistance in spontaneous bacterial peritonitis (SBP) in
      patients with chronic severe hepatitis].

PMID- 15975295
TI  - [Gene therapy for liver fibrosis].

PMID- 15975296
TI  - [Mechanism of transforming growth factor beta/Smad signaling and the relationship
      between its transduction and liver fibrosis].

PMID- 15975297
TI  - [Recent developments in the investigation of anti-liver fibrosis compositions of
      herbs].

PMID- 15975298
TI  - Research progress of liver diseases.

PMID- 15975300
TI  - Clinical observation of the effect of Xuesaitong soft capsule on post-hepatitis
      fibrosis.
AB  - OBJECTIVE: To study the effect of Xuesaitong soft capsule (XST) on liver fibrosis
      criteria in patients with post-hepatitis fibrosis. METHODS: Sixty-four patients
      with such fibrosis were randomly divided into the treated group and control
      group. They were treated with XST and Dahuang Zhechong pill (NFDA1) for 3 months
      respectively. Their liver fibrosis criteria were examined before and after
      treatment. RESULTS: The levels of serum procollagen III, hyaluronic acid,
      collagen IV, laminin in the two groups were significantly lower (P < 0.01) than
      those before treatment. The differences between the two groups were insignificant
      (P > 0.05). CONCLUSION: XST could recover liver dysfunction and had anti-liver
      fibrosis function.

PMID- 15975299
TI  - Two-year observation of the clinical efficacy in treating chronic hepatitis B
      Patients with Ganxian recipe and lamivudine.
AB  - OBJECTIVE: To evaluate the clinical efficacy of Ganxian recipe (GXR) and
      lamivudine (LVD) in a two-year treatment of chronic hepatitis B (CHB). METHODS:
      One hundred and twenty patients with CHB were randomly divided into the
      combinedly treated group (combined group) of 40 CHB patients who were treated
      with GXR combined with LVD. Another 40 CHB patients were treated with LVD alone
      (WM group), and still another 40 CHB patients were treated with GXR alone (TCM
      group). All these cases were randomly controlled and observed for two years.
      RESULTS: Comprehensive efficacy: Total effective rate of the combined group
      (complete response and partial response) was 92.5%, while that of the WM group
      was 67.5% and TCM group 57.5%, respectively, with the difference between them was
      significant (P < 0.01); after treatment, the hepatic functions (AST, ALT, SB) of
      the three groups were all reduced, and the reduction in the combined group was
      particularly significant in comparison with the WM group or TCM group, P < 0.05
      or P < 0.01 respectively, suggesting that the effect in the combined group was
      better than that in the other two groups; the rate of tyrosine-methionine
      aspartate-aspartate (YMDD) virus mutation: it was 7.5% in the combined group,
      40.0% in the WM group, and 5.0% in the TCM group; liver fibrosis improvement
      parameter: after treatment, the results in the combined group got better than
      those in the other two groups. CONCLUSION: GXR could inhibit the appearance of
      YMDD after long-term application of LVD, and combined use has marked synergism.

PMID- 15975301
TI  - Effects of Rebixiao granules on blood uric acid in patients with repeatedly
      attacking acute gouty arthritis.
AB  - OBJECTIVE: To observe the clinical effect of Rebixiao granule (RBXG) in treating
      repeatedly attacking acute gouty arthritis and through experimental study on
      blood uric acid to explore RBXG's therapeutic mechanism. METHODS: Ninety
      repeatedly attacking acute gouty arthritis patients were divided into the treated
      group (n = 60) and control group (n = 30). The treated group was treated with
      RBXG, and the control group was treated with Futalin tablets (diclofenac sodium).
      The baseline treatment including good rest, low purine diet, sufficient water
      drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine
      600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage
      to establish the animal models. RESULTS: The clinical effective rate of the
      treated group was 95.0% and that of the control 90.0%. Good therapeutic effects
      were won, insignificant difference (P > 0.05)was shown between the two groups.
      However, the cure rate of the treated group was 26.7% while that of the control
      group was 10.0%, with significant difference (P < 0.01) shown between them. The
      treated group had its blood uric acid lowered, which was significantly different
      (P < 0.05) from that of the control group. The animal experiment indicated that
      all the three groups treated with different dosages of RBXG, as well as the Ash
      bark and Smilax glabra rhizome groups had their blood uric acid content reduced
      in the hyperuricemic mice. CONCLUSION: RBXG has a quicker initiation and better
      treatment effects than sole anti-inflammatory and analgesic agents on the
      treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic
      or adverse reactions and therefore good for long-term administration and likely
      to be a safe TCM preparation to control the symptoms and reduce the onsets of
      repeatedly attacking of acute gouty arthritis. The animal experiment shows that
      both the compound preparation and part of the single ingredients in the recipe
      have the function of reducing blood uric acid. However, the compound recipe has
      better therapeutic effects, proving to be superior to single drugs.

PMID- 15975302
TI  - Study on Yangxue Qingnao granule in treating chronic cerebrovascular
      insufficiency.
AB  - OBJECTIVE: To observe the therapeutic effect of Yangxue Qingnao granule (YXQNG)
      in treating chronic cerebrovascular insufficiency (CCI) and its possible
      mechanism. METHODS: Eighty-three patients with CCI were randomly divided into
      YXQNG and nimodipine (ND) groups, the score of vertigo and the change in cerebral
      blood velocity before and after treatment were observed. And in the animal
      experiment, the authors adopted bilateral ligation of cervical carotid communis
      artery to establish CCI rat models in order to observe the effect of YXQNG and ND
      on incubation period of vertigo in rats and on memory performance. RESULTS: After
      clinical treatment, the vertigo score of YXQNG group was 2.34, and that of the ND
      group was 4.18, the comparison between the two groups showed that the difference
      was significant (P < 0.05). After treatment, the middle cerebral artery mean
      velocity (MCA Vm) of YXQNG group was 64.78 cm/s, vertebral artery mean velocity
      (VA Vm) was 29.78 cm/s, while that of ND group was 60.34 cm/s and 23.23 cm/s
      respectively, the comparison between these two groups showing statistical
      significance and the difference being obvious (P < 0.05). Experimental study
      showed that the rats in the model group after 12 weeks learning and memory were
      markedly lowered, the vertigo incubation period significantly lengthened, and
      compared with that of the model group, learning and memory of the YXQNG group was
      markedly improved and vertigo incubation period shortened, with the difference
      from that of the ND group insignificant, P > 0.05. CONCLUSION: YXQNG could
      effectively improve CCI patients' vertigo and other clinical symptoms and
      increase the cerebral blood flow, lessen the vertigo incubation of model group
      rats, elevate model group rats' memory performance.

PMID- 15975303
TI  - Effect of modified Sinisan on anorectal manometry of the constipation predominant
      type of irritable bowel syndrome.
AB  - OBJECTIVE: To explore the mechanism in patients with irritable bowel syndrome
      (IBS) of the constipation predominant type and observe the therapeutic effects of
      Sinisan (SNS). METHODS: Forty-seven IBS patients with the constipation
      predominant type were randomly divided into the treated group (n = 24) and the
      control group (n = 23). Another group of 22 healthy subjects was set up for
      healthy control. The treated group was treated with modified SNS, and the control
      group was treated with Cisapride, the therapeutic course for both groups was 8
      weeks. The changes of symptom scoring and anorectal manometry (the anorectal
      resting pressure, anal tract systolic pressure, anal tract diastolic pressure,
      rectal threshold feeling, maximal tolerance volume of rectum, and rectum
      compliance) of these two groups were recorded respectively and compared with each
      other. RESULTS: Compared with the healthy control group, the rectal threshold
      feeling, maximal tolerance volume of rectum and rectal compliance of the treated
      groups got reduced significantly before treatment (P < 0.05). After treatment,
      the symptom scoring, rectal threshold feeling and maximal tolerance volume of
      rectum were improved in both groups (P < 0.05), and the improvement of the
      treated group was more significant than that of the control group (P < 0.01). The
      total effective rate and recurrence rate of the treated group were superior to
      those of the control group significantly (P < 0.05, P < 0.01). CONCLUSION: SNS
      has good effect on IBS of the constipation predominant type.

PMID- 15975304
TI  - Clinical observation on Breviscapine in treating hypertension patients
      complicated with micro-albuminuria of renal impairment.
AB  - OBJECTIVE: To evaluate the efficacy of Breviscapine on essential hypertension
      (EH) patients complicated with micro-albuminuria of renal impairment. METHODS:
      Seventy-six EH patients were randomly assigned to the control group and the
      treated group, the former was given amlodipine, captopril/uropidil and the latter
      was given in addition Breviscapine intravenously dripped for 2 treatment courses.
      The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and
      urinary beta(2)-microglobulin (beta(2)-MG), and quantitative determination of 24
      hrs urinary protein were evaluated before and after treatment. RESULTS: In the
      control group, compared with before treatment, the quantitative determination of
      24 hrs urinary protein got reduced significantly (P < 0.05), while in the treated
      group, both urinary beta(2)-MG and quantitative determination of 24 hrs urinary
      protein got lowered significantly (P < 0.05 and P < 0.01). But after treatment,
      compared with the control group, urinary beta(2)-MG and quantitative
      determination of 24 hrs urinary protein in the treated group were obviously
      reduced (P < 0.05). CONCLUSION: Besides lowering blood pressure effectively,
      Breviscapine could improve the renal function significantly and reduce the
      urinary micro-albuminuria, hence showing promising effect on renal protection.

PMID- 15975305
TI  - Follow-up efficacy of integrative Chinese and Western drugs on localized
      scleroderma with vitamine B6 and Xuefu Zhuyu decoction.
AB  - OBJECTIVE: To investigate the therapeutic effects of vitamine B(6) (Vit B(6)) and
      Xuefu Zhuyu Decoction (XFZY, for activating blood circulation to remove stasis)
      in patients with localized scleroderma(LSD). METHODS: Thirty-three patients were
      treated with XFZY and Vit B(6), with 15 cases taking orally prednisone acetate
      and 20 healthy volunteers as the control. Their level of soluble interleukin-2
      receptor (sIL-2R) and tumor necrosis factor-alpha (TNF-alpha) in the patients
      with LSD before and after treatment were observed. RESULTS: The level of sIL-2R
      and TNF-alpha in the serum from the patients with LSD were higher than those of
      healthy volunteers (P < 0.01). After treatment with Vit B(6) and XFZY, the level
      of sIL-2R and TNF-alpha from the patients with LSD decreased significantly (P <
      0.01), but there were no difference between the group taking Vit B(6) plus XFZY
      and the group given prednisone. CONCLUSION: The activating blood circulation to
      remove stasis approach in treating LSD with integrative Chinese and Western drugs
      got better results, and metabolic disorder of tryptophan might be correlated with
      the etiology of LSD.

PMID- 15975306
TI  - Study on the therapeutic mechanism of the active principle of the Chinese drug
      Paeoniae Radix 801 through affinity biosensors IAsys plus quartz crystal
      microbalance.
AB  - OBJECTIVE: To study the targeted point and mechanism of the function of the blood
      activating and stasis-removing Chinese drugs, Paeoniae Radix 801(PR801) in its
      cardiovascular protective effects and its specific binding with endothelin 1 (ET
      1) as well as the dynamics of the two's interactive function by means of using
      affinity biosensors: IAsys Plus and quartz crystal microbalance (IAQCM). METHODS:
      ET-1 was immobilized on the surfaces of IAQCM by using the new surface
      modification methods. The PR801 in the solution was detected by modified
      substrates and the specific binding between PR801 and ET-1 was studied. RESULTS:
      The curves went up or down after adding PR801. There is specific binding between
      PR801 and ET-1. The bound mass were 0.458 ng/mm(2) and 133.54 ng/cm(2),
      respectively. There exists relatively good stability with these two methods.
      CONCLUSION: The affinity biosensors: IAQCM can be used to study the interaction
      mechanism between PR801 and ET-1, providing a new way to study the interaction
      mechanism of TCM. PR801 can bind ET-1 specifically in the experiments. Therefore,
      ET-1 is another target that PR801 can bind specifically besides thromboxane A(2).

PMID- 15975307
TI  - Effects of Jiantaiye on estrogen receptor and mRNA expressions in uterus of mice
      with embryo implantation dysfunction.
AB  - OBJECTIVE: To explore the effect of Jiantaiye (JTY) on the expression of estrogen
      receptor (ER) and ER mRNA in uterus of mice with embryo implantation dysfunction.
      METHODS: Embryo implantation dysfunction mouse models were induced with
      mifepristone and treated with JTY. All animals were sacrificed on day 8 of
      pregnancy. The endometrial ER and ER mRNA expressions were assessed by
      immunnohistochemical SP method and semi-quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: Area ratio and absorbency of ER in
      the JTY treated group's gland and stroma were higher than those of the model
      group, quite similar to those of the normal control's, and ER mRNA expression in
      treated group's uterus was significantly higher than that in the models, but it
      was not significantly different from the normal control. CONCLUSION: JTY improves
      the endometrial development by increasing ER and ER mRNA expressions of uterus of
      mice with embryo implantation dysfunction.

PMID- 15975308
TI  - Study on the analgesic effect and mechanism of Zhitong capsule in adjuvant
      arthritis rats.
AB  - OBJECTIVE: To observe the analgesic effect of Zhitong Capsule (ZTC) and study its
      mechanism in adjuvant arthritis (AA) rats. METHODS: Forty-eight male Sprague
      Dawley rats were randomly divided into six groups with 8 rats in each group. On
      the first day, except to those in the normal group that were treated with normal
      saline, the same amount of Freund's complete adjuvant (FCA) was given through
      intradermal injection into the right hind paw to all the rats in the other
      groups. From the 17th day of the modeling on, the rats in groups of ZTC were
      administered daily through gastrogavage with a dose of 1000, 500, 250 mg/kg
      respectively, while equal volume of normal saline was given to those in the
      normal group and model group, and an equal volume of aspirin (ASA) solution was
      given to rats in the ASA group through gastrogavage for 10 days, once per day,
      and on the 27th day, the analgesic effect of ZTC was measured with heat withdraw
      method. The activities and contents of superoxide dismutase (SOD) and lipid
      peroxides (LPO) in serum were observed by spectrophotometry, and the level of
      beta-endorphin (beta-EP) in hypothalamus were determined by the assay of
      immunohistochemistry. RESULTS: ZTC showed significant effects on enhancing the
      pain threshold and at the same time it increased the activities of SOD and
      reduced the contents of LPO in serum. ZTC could also increase the level of beta
      EP in hypothalamus. CONCLUSION: ZTC has analgesic effect and its mechanism is
      probably related with its effect in inhibiting the level of oxygen free radicals
      in serum and increasing the level of beta-EP of hypothalamus in rats.

PMID- 15975309
TI  - Protective effect of Jiechangning decoction in treating experimental ulcerative
      colitis in guinea pigs.
AB  - OBJECTIVE: To study the therapeutic effects and mechanism of Jiechangning (JCN)
      decoction on carrageenan induced experimental ulcerative colitis (UC). METHODS:
      After sensitizing guinea pigs with carrageenan, we established UC animal models
      by free drinking water containing 2% acid degraded carrageenan (ADC). JCN
      decoction was orally administered once a day for 2 weeks after carrageenan
      treatment. Salicylazosulfapyridine (SASP) and normal saline were given to the
      other two groups as control. The levels of colon lipid peroxide (LPO), acid
      phosphatase (ACP) activity and tumor necrosis factor-alpha (TNF-alpha) were
      measured; colitis activity score (CAS) was carried out for assessment of the
      degree of tissue inflammation and injury; the colonic pathological changes were
      examined simultaneously with hematoxylin and eosin (HE) and toluidine blue
      staining used to evaluate the therapeutic effects of JCN decoction and SASP.
      RESULTS: Experimental colitis models resembling human UC were successfully
      induced. The levels of tissue LPO, ACP activity and the content of tissue TNF
      alpha were markedly increased in the model group as compared with the normal
      control group (P < 0.01) and were positively correlated with CAS. JCN decoction
      could reverse these changes like SASP. HE staining showed that JCN decoction and
      SASP could reduce CAS and the degree of tissue injury, toluidine blue staining
      revealed that mucosa and submucosa red metachromasia pellets in JCN group and
      SASP group were markedly fewer than those in the model group. CONCLUSION: JCN
      decoction is effective in treating experimental UC, which provides theoretical
      basis for its clinical application.

PMID- 15975310
TI  - An experiment on standardized cell culture assay in assessing the activities of
      Composite Artemisia Capillaris Tablets against hepatitis B virus replication in
      vitro.
AB  - OBJECTIVE: To explore the activities of Composite Artemisia Capillaris Tablet
      (CACT) against hepatitis B virus replication in vitro. METHODS: By means of
      radioimmunoassay (RIA), Dot blot and Southern blot, the surface and e antigen
      production of 2.2.15 cells, HBV DNA in 2.2.15 cell culture medium and that in
      2.2.15 cells were examined respectively. RESULTS: HBsAg, HBeAg values of 2.2.15
      cells treated by CACT were lower than those of the control, the HBV DNA
      quantities in culture medium and in 2.2.15 cells decreased as compared with those
      cells with no treatment by CACT given to them. CONCLUSION: CACT could inhibit HBV
      DNA replication, showing its potential antiviral activity in hepatitis B
      treatment.

PMID- 15975311
TI  - Effects of total flavone of Abelmoschl Manihot L. Medic on the function of
      platelets and its mechanism.
AB  - OBJECTIVE: To study the effects of total flavone of Abelmoschl Manihot L. Medic
      (TFA) on the function of platelets and to explore its mechanism. METHODS: Rat
      models of artery-veins bypassing thrombus formation were used. The platelets of
      rabbits were collected. Platelet aggregation was induced by collagen and
      intracellular calcium ion concentration ([Ca(2+)]i) was assayed by Fura-2 method.
      RESULTS: TFA (25, 50, 100 mg/kg) significantly and dose-dependently reduced the
      weight of thrombus. TFA (0.025, 0.05, 0.1 mg/ml) possessed dose-dependant
      inhibitory effects on rabbits' platelet aggregation induced by collagen. TFA
      significantly reduced the resting and CaCl(2)-induced increase of free
      intracellular calcium concentration ([Ca(2+)]i) in rabbit platelet in vitro.
      CONCLUSION: TFA has an antiplatelet effect via the inhibition on the influx of
      Ca(2+).

PMID- 15975312
TI  - Clinical study on the effect of Shengxueling on idiopathic thrombocytopenic
      purpura.
AB  - OBJECTIVE: To observe the clinical effect of Shengxueling (SXL) on idiopathic
      thrombocytopenic purpura (ITP), and study the possible mechanism. METHODS: Eighty
      six cases of ITP were randomly divided into two groups. The SXL group, 56
      patients treated with SXL, a traditinal Chinese medicine and 30 patients
      administered with prednisone were taken as control. Each group took drugs for 3
      months and was under follow-up observation. RESULTS: In the SXL group, the total
      effective rate was 85.71%, similar to prednisone 83.33% (P > 0.05) for 3 months,
      but the total effective rate of SXL (91.07%) were obviously better than that of
      the control group (53.33%) (P < 0.01) for 6 months and had no obvious adverse
      reaction. The patients bleeding was alleviated or stopped, the general condition
      was improved. At the same time, blood platelet count (PLT) was increased,
      platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly
      dropped, the level of natural killers cells activity (NKa) increased, the rate of
      T lymphocyte subsets gradually returned to normal level. Megakaryocyte tended to
      maturation on bone marrow smear after treatment. All differences above were
      statistically significant. CONCLUSION: SXL is an effective and safe medicine for
      ITP. Its mechanism could regulate cytoimmune, inhibit platelet antibody to reduce
      the destruction of platelet, increase the number of platelet, promote the
      division and maturation of megakaryocyte, facilitate the production and release
      of platelet, lower the fragility of capillary, prevent and cure hemorrhagic
      tendency.

PMID- 15975313
TI  - Study of the effect of leeching on plasma endothelin and soluble interleukin-2
      receptor in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: to explore the mechanism of leeching in treating systemic lupus
      erythematosus (SLE). METHODS: Forty-four patients with SLE were randomly divided
      into conventional corticosteroid treated group (control group, n = 20) and
      conventional treatment group with leeching intervention added (leeching group, n
      = 24). Before and after treatment the concentration of plasma endothelin (ET) and
      soluble interleukin-2 receptor (sIL-2R) were determined. RESULTS: Before
      treatment the level of plasma ET and sIL-2R in the SLE patients were all higher
      than those in the normal healthy group, (P < 0.01). But after treatment the level
      of these in both groups were significantly improved than those of before
      treatment (P < 0.05), and comparison between these two treated groups showed that
      the difference between them was significant (P < 0.05). CONCLUSION: Leeching
      added to conventional treatment of SLE could be more effective in improving the
      level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.

PMID- 15975314
TI  - Effect of the principle of activating blood circulation to break stasis on GMP
      140 and D2 dimer in patients with acute cerebral infarction.
AB  - OBJECTIVE: To explore the clinical efficacy of the principle of activating blood
      circulation to break stasis (ABCBS) and its influence on platelet membranous
      protein particle (GMP-140) and D(2) dimer (D-dimer) before and after treatment.
      METHODS: Eighty-eight patients with blood stasis syndrome (BSS) of acute cerebral
      infarction (ACI) were randomly divided into two groups, both of which were
      treated with conventional treatment, i.e. with western medicine (WM), with Salvia
      injection added through intravenously dripping. One of the two groups was used as
      the control and the other group as the treated group who had ABCBS herbs orally
      taken in addition. The duration of treatment course for both groups was 3 weeks.
      RESULTS: There were changes in both groups over clinical symptoms, nerve function
      deficit scoring and GMP-140, D-dimer, but the treated group showed significantly
      better than that of the control group, (P < 0.05). CONCLUSION: ABCBS principle
      could serve as an important auxiliary treating method for BSS of ACI, as it can
      effectively alter the blood of ACI patients which was viscous, condense,
      coagulant and aggregating.

PMID- 15975315
TI  - Regulative effect of traditional Chinese medicine on gene-expression related to
      precancerous lesion of gastric cancer.
AB  - The gene-expression changes related with precancerous lesion of gastric cancer
      (PLGC) are surveyed. Not only the regulative effect of traditional Chinese
      medicine (TCM) on oncogene, antioncogene and anti-apoptosis gene that are related
      with PLGC is analyzed, but also current research state is presented. It's showed
      that TCM has effects of therapy and inversion on PLGC. These effects are related
      with the inhibition to related oncogene expression, the regulation and activation
      to the deletion of antioncogene, the inhibition to the high-expression of mutant
      gene-protein about antioncogene, and the regulative function to anti-apoptosis
      gene.

PMID- 15975316
TI  - Targeting healthcare disparities: an integrated model to improve treatment rates
      of dyslipidemia in African American patients.

PMID- 15975317
TI  - Transesophageal echocardiography and stroke.
AB  - Only coronary artery disease and cancer kill more people than stroke in the
      United States. Transesophageal echocardiography (TEE) is a semi-invasive
      ultrasound cardiac imaging technique that provides superior anatomic detail as
      well as functional information. Searching for a cause of cerebral ischemia is the
      most common indication for TEE in cardiac ultrasound laboratories. Although TEE
      is not superior to transthoracic imaging for identifying all sources of cardiac
      embolism, its ability to more sensitively detect atrial septal aneurysm, patent
      foramen ovale, and aortic atheroma has been well described in recent years. Care
      must be exercised in using TEE to identify suspected cardiac sources of embolism,
      as potential etiologies described in the literature are not equally established
      by rigorous clinical trials. Confidence level in cause and effect for any cardiac
      pathology identified must be factored into therapeutic decisions.

PMID- 15975318
TI  - Stroke as a complication of congenital heart disease.
AB  - Patent foramen ovale is a common finding in the general population. It is
      associated with an increased risk of stroke, but it may not have a significant
      effect on recurrent stroke risk in medically treated patients. Recently, many
      questions have arisen with respect to best treatment for preventing recurrent
      stroke. Some data from a clinical trial of anticoagulation compared with
      antiplatelet therapy support antiplatelet treatment for secondary prevention.
      There are not enough data currently to support surgical or percutaneous closure
      of patent foramen ovale for stroke prevention.

PMID- 15975319
TI  - Neuroprotective role of neurotrophins: relationship between nerve growth factor
      and apoptotic cell survival pathway after cerebral ischemia.
AB  - Neurotrophins provide a neuroprotective effect in a variety of brain diseases.
      Recent reports demonstrate that neurotrophins play an important role in the
      regulation of apoptotic neuronal cell death and in the relationship between this
      machinery and activation of cell survival pathways. The cascade reactions of the
      two major cell survival pathways, mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase, are known to play a critical role in the
      regulation of apoptotic neuronal cell survival pathways. Neurotrophins such as
      nerve growth factor regulate these two cell survival pathways in in vitro
      studies. However, the role of neurotrophins in cell survival remains unclear in
      in vivo apoptotic neuronal cell death. We discuss the mechanism of
      neuroprotection by neurotrophins and also discuss cell survival effect of nerve
      growth factor on apoptotic neuronal cell death after in vivo cerebral ischemia.

PMID- 15975320
TI  - Evolving concepts regarding transient ischemic attacks.
AB  - Transient ischemic attack (TIA) represents one end of the spectrum of focal brain
      ischemia, the other being completed infarction or ischemic stroke. The evolving
      technologic advancements in neuroimaging continue to change and sharpen the
      definition, epidemiology, and management of TIA. As a powerful risk factor for
      ischemic stroke, TIA deserves widespread public and physician education, urgent
      attention and investigation, and rapid management. The recognition and treatment
      of TIA provides an excellent opportunity for stroke prevention that is often
      missed or poorly recognized among physicians.

PMID- 15975321
TI  - Incidence and etiology of cerebrovascular disease in patients with malignancy.
AB  - Cerebrovascular disease is common in cancer patients and often arises from
      mechanisms unique to malignancy. Direct tumor effects include intratumoral
      hemorrhage, arterial and venous sinus invasion by tumor mass or leptomeningeal
      infiltrates, and tumor emboli. Complications of chemotherapy, radiation therapy,
      and hematopoietic stem-cell transplantion for cancer can occur before, during, or
      years after treatment. Coagulopathic conditions involve disseminated
      intravascular coagulation, thrombocytopenia, nonbacterial thrombotic
      endocarditis, and cerebral intravascular coagulation. Finally, septic infarction
      from fungal or bacterial sepsis and infectious vasculitis manifest in cancer
      patients immunocompromised by malignancy or cancer therapy. In many cases a
      combination of mechanisms is causative, and both hemorrhagic and ischemic stroke
      can occur simultaneously. Stroke type and mechanism, as well as the stage and
      pathology of the neoplasm, dictate proper management and help delineate
      prognosis.

PMID- 15975322
TI  - Determinants of mortality in stroke patients with right brain damage.
AB  - Stroke is the world's second leading cause of mortality and long-term disability.
      Damage to the nondominant right brain has distinct clinical characteristics. The
      resultant cardiovascular and autonomic dysfunction peculiar to right hemispheric
      stroke can adversely affect the short- and long-term outcome of stroke victims.
      Blood flow characteristics to the right hemisphere may also put the right brain
      at more risk for embolic and silent infarcts.

PMID- 15975323
TI  - Decompressive craniectomy as a therapeutic option in the treatment of hemispheric
      stroke.
AB  - Even though severe hemispheric stroke represents a small subtype of ischemic
      stroke, the extreme morbidity and mortality necessitate aggressive management
      strategies to improve outcome. Decompressive craniectomy is an important
      therapeutic tool with demonstrated effects in significantly reducing intracranial
      hypertension and mortality from herniation related to cerebral edema and elevated
      intracranial pressure. Its effect on functional outcome and quality of life
      varies, but there is evidence to suggest beneficial effects in younger patients
      and in patients treated earlier. Although more prospective data are required to
      further identify specific indications for the procedure, it represents an
      important tool in treatment of nondominant hemispheric stroke.

PMID- 15975324
TI  - Magnetic resonance imaging: implication in acute ischemic stroke management.
AB  - Multimodality magnetic resonance imaging (MRI) techniques, including diffusion
      weighted imaging (DWI), perfusion-weighted imaging (PWI), fluid-attenuated
      inversion recovery (FLAIR), T2 susceptibility imaging, and magnetic resonance
      angiography (MRA), quickly provide accurate information about ischemic penumbra
      (DWI/PWI mismatch), tissue perfusion, and vascular localization in acute stroke
      setting. These techniques help physicians to select the proper candidates for
      thrombolysis and/or neuroprotective treatment to salvage tissue at risk
      (mismatch) and monitor acute stroke patients after treatment. Recent and ongoing
      trials demonstrate the benefit of treating acute stroke patients depending on
      tissue at risk of infarction rather than timing of onset. These techniques will
      extend timing to salvage ischemic brain tissue beyond the 3-hour window. MRI is a
      powerful tool for managing acute stroke patients and helps elucidate the
      pathophysiology of cerebral ischemia in a given patient.

PMID- 15975325
TI  - Statins and stroke prevention.
AB  - Data from studies on the benefits of statins in coronary artery disease patients
      in preventing recurrent primary and secondary cardiac endpoints, as well as
      ischemic strokes, imply the potential value of statins in recurrent ischemic
      stroke prevention without coronary artery disease symptoms or, by extension,
      primary ischemic stroke prevention. However, data on the latter are lacking,
      although the ongoing Stroke Prevention by Aggressive Reduction in Cholesterol
      Levels (SPARCL) study is designed to answer that question. Until these data
      become available, clinicians are justified in using statins to avert recurrent
      ischemic strokes due to atherosclerosis, especially if elevated total
      cholesterol, increased low-density lipoprotein cholesterol, and/or reduced high
      density lipoprotein cholesterol, as specified in the National Cholesterol
      Education Program Third Adult Treatment Panel, are present. This article reviews
      the pathophysiology of atherosclerosis, particularly the major components of
      atheromas of cholesterol, smooth muscle cells, inflammation, "foam cells," and
      connective tissue elements. Emphasis is placed on the first three and the results
      of statin trials in coronary artery disease, as well as the beneficial
      pleiotrophic effects of statins in ischemic strokes.

PMID- 15975326
TI  - Randomized clinical stroke trials in 2004.
AB  - Randomized clinical stroke trials published during 2004 dealt primarily with
      prevention of strokes by reducing risk factors. The usefulness of innovative
      versions of widely known treatment modalities was documented. These included
      angiotensin-converting enzyme inhibitors against hypertension, acarabose against
      diabetes, and the antiplatelet agent triflusal instead of aspirin. A large
      British study confirmed the value of treatment with simvastatin. Appropriately
      powered studies found no benefit for stroke prevention of either vitamin
      treatment to lower homocysteine or hormonal replacement in post-menopausal women.
      The circumstances under which antithrombotic, anticoagulant and surgical
      treatments of acute ischemic stroke are appropriate were further specified.

PMID- 15975327
TI  - Reversible tricuspid valve stenosis due to a metastatic dissemination of a
      noncardiac sarcoma.
AB  - Malignant disease is present in the pericardium of 1.5% to 20.6% of patients
      dying of malignant diseases as was examined postmortem. We present a case of a 57
      year-old man with a history of Hodgkin's disease and a sarcoma of gluteus who
      presented with tachypnea, generalized weakness, and anasarca for 7 days. The
      echocardiogram revealed the presence of a significant pericardial thickening and
      localized pericardial effusion resulting from a tricuspid stenosis. A right
      anterior thoracotomy was performed, and a pericardiectomy (4 x 4 cm) was done.
      The histologic examination of the pericardium revealed the presence of a
      metastatic dissemination from a sarcoma. The cause for the clinical presentation
      and the treatment of malignant pericardial disease are discussed.

PMID- 15975328
TI  - Benign oncocytoma of the trachea.
AB  - A 16-year-old girl was referred with a presumed muco-epidermoid carcinoma of the
      distal trachea, which was diagnosed by bronchoscopic biopsy. She underwent
      tracheal resection and end-to-end anastomosis. Final pathologic examination of
      the resected specimen revealed a benign oncocytic adenoma. This neoplasm is
      composed predominantly of oncocytes and is extremely rare in this location.

PMID- 15975330
TI  - Off-label use of recombinant factor VIIA concentrates after cardiac surgery.

PMID- 15975331
TI  - Using a miniaturized circuit and an asanguineous prime to reduce neutrophil
      mediated organ dysfunction following infant cardiopulmonary bypass.
AB  - BACKGROUND: Contemporary infant cardiopulmonary bypass circuits require a blood
      prime. Blood, especially when stored, generates an inflammatory response, and may
      contribute to organ dysfunction following cardiopulmonary bypass. We determined
      whether using a miniaturized circuit and an asanguineous prime attenuated the
      post-bypass inflammatory response, and improved right ventricular and pulmonary
      function. METHODS: Sixteen infant piglets were placed into 3 groups based on
      prime components: group I (fresh blood), group II (stored blood), and group III
      (miniaturized circuit and asanguineous prime). Piglets were placed on
      cardiopulmonary bypass (100 mL.kg(-1).min(-1)), cooled to 18 degrees C, and
      underwent continuous perfusion (50 mL.kg(-1).min(-1)) for 30 minutes. They were
      rewarmed and separated from bypass. Serum tumor necrosis factor-alpha, right
      ventricular function, and pulmonary function were measured before and 30 minutes
      after bypass. Neutrophil priming activity in fresh and stored donor blood was
      also assessed. RESULTS: Animals in group III had significantly improved
      cardiopulmonary function than the groups receiving blood (right ventricular
      cardiac index [mL.kg(-1).min(-1)]: group I [18.8 +/- 4.8], group II [21.5 +/-
      6.2], and group III [81.2 +/- 11.4], p < 0.001; and pulmonary vascular resistance
      index [dynes.mL(-1).kg(-1)]: group I [1169 +/- 409], group II [1610 +/- 486], and
      group III [214 +/- 63], p = 0.03). Tumor necrosis factor-alpha (pg.mL(-1)) was
      lower in group III (1465 +/- 39) than in the groups receiving blood (3940 +/-
      777), p = 0.002. Neutrophil priming activity (nmol.min(-1)) was also higher in
      stored blood (3.7 +/- 6) than in fresh blood (1.9 +/- 0.2), p = 0.02.
      CONCLUSIONS: We have devised a unique miniaturized circuit that allows an
      asanguineous prime without hemodilution in an infant swine model. The employment
      of this circuit attenuates the post-bypass inflammatory response and has salutary
      effects on cardiopulmonary function.

PMID- 15975332
TI  - Extracorporeal life support in neonates, infants, and children after repair of
      congenital heart disease: modern era results in a single institution.
AB  - BACKGROUND: Extracorporeal life support has assumed a very effective role in the
      support of patients with refractory heart failure after repair of congenital
      heart disease, with hospital survival between 37% and 42%. We reviewed our
      results of different applications of extracorporeal life support in the last 2
      years. METHODS: Between January 2001 and October 2003, 671 patients underwent
      surgery for congenital heart disease at our institution. We retrospectively
      reviewed the hospital and clinic charts of the patients who required
      extracorporeal life support postoperatively, and studied the factors associated
      with survival. RESULTS: Thirty-six patients (5.36%) received extracorporeal life
      support after surgery, between 1 day and 8 years of age (age < 30 days, n = 34).
      We divided the patients into four groups. Group 1 consisted of 13 patients who
      were electively placed on ventricular support without an oxygenator
      (univentricular assist device) after repair of single-ventricle disease. Group 2
      consisted of 16 patients who required extracorporeal membrane oxygenation after
      surgery for failed hemodynamics. Group 3 consisted of 2 patients who required
      left ventricle support (left ventricular assist device) after surgery for two
      ventricle disease but who did not require biventricular (extracorporeal membrane
      oxygenation) support. Group 4 consisted of 5 patients who required conversion
      from ventricular assist device to extracorporeal membrane oxygenation. Overall,
      28 patients were weaned successfully (78%), and 24 survived to discharge (67%).
      Hospital survival in groups 1, 2, 3, and 4 was 100%, 50%, 100%, and 20%,
      respectively. Univariate factors associated with survival were age, weight,
      ventricular assist device type, duration, single-ventricle disease,
      reexploration, number of complications, and specific complications such as
      sepsis, renal failure, and pulmonary failure. CONCLUSIONS: Extracorporeal life
      support utilization was expanded to include different applications with different
      outcomes. The extracorporeal life support registry should be altered to reflect
      those changes.

PMID- 15975333
TI  - High flow rates during modified ultrafiltration decrease cerebral blood flow
      velocity and venous oxygen saturation in infants.
AB  - BACKGROUND: The intracranial hemodynamic effects of modified ultrafiltration in
      children are unknown. We investigated the effects of different blood flow rates
      during modified ultrafiltration on the cerebral hemodynamics of children with
      weights above and below 10 kg. METHODS: Thirty-one children (weights: < or = 10
      kg, n = 21; > 10 kg, n = 10) undergoing cardiopulmonary bypass were studied.
      Middle-cerebral artery blood flow velocities and cerebral mixed venous oxygen
      saturations were measured before, five minutes from the beginning, and at the end
      of ultrafiltration. Patients were classified according to their blood flow rates
      during ultrafiltration in three groups: high (> or = 20 mL/kg/min), moderate (10
      19 mL/kg/min), and low flow rates (< 10 mL/kg/min). RESULTS: During modified
      ultrafiltration, blood pressures and hematocrit increased (p < 0.001), but
      cerebral blood flow velocities and mixed venous oxygen saturations decreased (p <
      0.001). A significant correlation was found between blood flow rates of
      ultrafiltration and the decline in mean cerebral blood flow velocity (r = - 0.48;
      p = 0.005) and cerebral oxygen saturation (r = - 0.49; p = 0.005) or hematocrit
      increase (r = 0.59; p = 0.001). Infants exposed to high flow rates had greater
      reduction of cerebral blood flow velocity and regional mixed venous saturation
      and higher hematocrit at the end of ultrafiltration compared with those subjected
      to moderate and low flow rates (p < 0.04). No significant difference was found
      between moderate and low flow groups. The flow rate of ultrafiltration was the
      only independent predictor of the changes in cerebral mixed venous oxygen
      saturation (p = 0.033). CONCLUSIONS: High blood flow rates through the
      ultrafilter during modified ultrafiltration transiently decrease the cerebral
      circulation in young infants compared with lower blood flow rates. These effects
      may be related to an increased diastolic runoff from the aorta into the
      ultrafiltration circuit that leads to a "stealing" effect from the intracranial
      circulation, which may be important in infants with dysfunctional cerebral
      autoregulation.

PMID- 15975334
TI  - Invited commentary.

PMID- 15975335
TI  - Atrioventricular valve procedures with repeat fontan operations: influence of
      valve pathology, ventricular function, and arrhythmias on outcome.
AB  - BACKGROUND: The purpose of this study is to analyze atrioventricular valve
      procedures when performed in association with repeat Fontan operations and to
      determine the influence of atrioventricular valvar pathology, ventricular
      function, and arrhythmias on outcome. METHODS: Between December 1994 and August
      2004, 80 patients had repeat Fontan operations that included arrhythmia surgery
      (78 of 80), venous pathway revision (78 of 80), atrioventricular valve repair
      replacement (15 of 80), and other associated procedures. Mean ages were the
      following: at operation, 20.3 +/- 8.4 years; at prior Fontan, 7.1 +/- 5.8 years.
      Atrioventricular valve procedures were performed on 8 functionally mitral and 7
      functionally tricuspid valves. The average cross-clamp and cardiopulmonary bypass
      times were 61.9 +/- 42.8 minutes and 218 +/- 82 minutes, respectively. RESULTS:
      Ventricular dysfunction (8% vs 54%, p < 0.0001), valvar dysfunction (13% vs 25%,
      p < 0.05), and atrial arrhythmias (18% vs 86%, p < 0.0001) increased during the
      preceding 12.0 +/- 4.7 years before the most recent Fontan operation.
      Multivariate analysis for death, orthotopic cardiac transplantation (OCT), or
      renal dialysis showed severe ventricular dysfunction, age greater than 25 years,
      right or ambiguous functional ventricle, and ischemic time greater than 100
      minutes to be highly significant. Notably, cardiac index, elevated end diastolic
      pressure, and atrial fibrillation were not predictors of outcome. Mitral valve
      repairs were inconsistent due to probable technical misjudgments; most tricuspid
      valves could not be repaired. Operative and late mortality were 1.2% and 5.0%,
      respectively. Emergent and late OCT were 1.2% and 3.7%, respectively.
      CONCLUSIONS: Risk factors for poor outcome are severe ventricular dysfunction,
      right or ambiguous single ventricle, age greater than 25 years, and ischemic time
      greater than 100 minutes. Mitral valves are potentially more amenable to repair
      than are tricuspid valves. Prosthetic valve replacement should be considered when
      valve repair is questionable.

PMID- 15975336
TI  - Seven-year clinical experience with the extracardiac pedicled pericardial Fontan
      operation.
AB  - BACKGROUND: Although improved perioperative outcomes with growth potential of the
      extracardiac pedicled pericardial Fontan (EPPF) operation have been suggested, no
      advantage has been demonstrated. METHODS: We retrospectively reviewed our
      institutional experience of 54 consecutive patients undergoing EPPF between June
      1996 and August 2003. Clinical and echocardiographic follow-up was obtained
      yearly with a mean follow-up of 2.8 +/- 2.0 years. RESULTS: There were 29 males,
      median age 3.3 years (2-6.8). Median cardiopulmonary bypass time was 79 min (39
      295). Fibrillatory arrest was used briefly in 9 patients, of which 6 were for
      fenestration. One Fontan required takedown (1.8%) and there was 1 death (1.8%)
      from Candida mediastinitis. Median intensive care unit stay, hospital length of
      stay, and chest tube drainage were 4 days, 12 days, and 8 days, respectively.
      Arrhythmias occurred in 7 patients. Three (5.6%) of these had preexisting Holter
      abnormalities requiring permanent pacemaker implantation. Freedom from
      thromboembolic events, reoperation, and death at 2.8 years after discharge were
      96.2%, 98.1%, and 100%, respectively. All patients were New York Heart
      Association class I-II, with median oxygen saturation of 94 %. Only 5 patients
      (9.4%) had mild self-restricted activities. Echocardiographic evaluation revealed
      excellent ventricular function and flow dynamics. CONCLUSIONS: At midterm follow
      up this technique yields outcomes as good as the other Fontan techniques and with
      further follow-up may prove to be superior. However, at this point no clear
      advantage has been demonstrated. The low rate of complications and potential for
      growth are appealing features of this procedure.

PMID- 15975337
TI  - Improved interstage mortality with the modified Norwood procedure: a meta
      analysis.
AB  - BACKGROUND: Modification of the Norwood procedure has been reported to improve
      immediate postoperative mortality compared with the classic Norwood. Interstage
      mortality has not been shown to be improved with the modified Norwood probably
      because of the small number of patients from each institution. The goal of this
      study was to determine if meta-analysis would provide sufficient data to prove
      statistical difference in interstage mortality for the modified Norwood
      procedure. METHODS: PubMed was searched using six different terms individually
      for articles from January 2003 to October 2004. Manuscripts that compared the
      classic to modified Norwood were reviewed. Mantel-Haenszel analysis was used to
      evaluate the relationship between treatment method and mortality stratified
      across hospitals. The Breslow-Day procedure tested homogeneity of odds ratio
      across hospitals. Separate analyses were performed for inpatient and interstage
      periods. RESULTS: A total of 4,545 citations was screened. Five manuscripts met
      the criteria. Seventy-two patients undergoing classic Norwood and 84 patients
      undergoing modified Norwood survived to initial hospital discharge. The Breslow
      Day statistic supported homogeneity of odds ratios for survival across hospitals
      (chi2 = 2.09, df = 4, p = 0.72). Odds of interstage death was 11.6 times greater
      (2.2 to 62.1, 95% CI) for the classic Norwood compared with the modified Norwood
      procedure. This difference was statistically significant by the Mantel-Haenszel
      chi2 (11.0, p = 0.001). The Breslow-Day statistic supported homogeneity of the
      odds ratios across hospitals (chi2 = 3.1, df = 4, p = 0.53). CONCLUSIONS: The
      modified Norwood procedure has a significantly lower interstage mortality
      compared with the classic Norwood procedure. A large randomized study is needed
      to determine whether these results remain consistent.

PMID- 15975338
TI  - Late assessment after biventricular repair for isomerism heart.
AB  - BACKGROUND: Although biventricular repair is theoretically ideal for the
      treatment of isomerism heart, the long-term outcome is unknown. We assessed the
      outcome of biventricular repair for atrial isomerism. METHODS: From 1984 to 2002
      in our surgical database, 10 of 67 patients with atrial isomerism received
      biventricular repair. The age at operation was 7.7 +/- 9.1 years. Preoperative
      ventricular volume was normal in all patients. Left ventricular ejection fraction
      was 62% +/- 8%. Intra-atrial rerouting was required in 8. The atrioventricular
      septal defect with double-outlet right ventricle was closed using comma-shaped
      intraventricular conduit in 8. Other procedures included pulmonary valvotomy and
      infundibulectomy in 2, transannular patch in 1 and right ventricle to pulmonary
      artery conduit in 1. RESULTS: There was one early death due to hemolytic
      phagocytic syndrome. The other 9 patients are in New York Heart Association class
      I at 12.7 +/- 5.3 years postoperatively. There was no atrial baffle stenosis
      except in 1 patient; it was successfully treated by stent placement 10 years
      after the operation. There was no incidence of left ventricular outflow
      obstruction. Mitral replacement (4 months postoperatively) or repair (15 years
      postoperatively) was done in 2 patients. The other 5 patients with
      atrioventricular septal defect showed trivial to mild regurgitation in the long
      term period. Arrhythmia was observed in 5 (left 4, right 1). Catheter ablation
      was needed in a patient with atrial flutter. Three of 9 patients require
      diuretics or digitalization, or both. CONCLUSIONS: The long-term outcome of the
      biventricular repair for atrial isomerism was excellent. Late development of
      mitral regurgitation and arrhythmia could be managed adequately.

PMID- 15975339
TI  - Predictive value of intraoperative transesophageal echocardiography in complete
      atrioventricular septal defect.
AB  - BACKGROUND: Intraoperative transesophageal echocardiography and follow-up
      transthoracic echocardiography have been useful in assessing cardiac function in
      complete atrioventricular septal defects. However, it has been suggested that a
      discrepancy exists between intraoperative and postoperative findings, and that
      intraoperative findings cannot reliably predict long-term results. This study
      aims to determine whether this discrepancy exists and to assess whether it is
      possible to predict follow-up results using intraoperative transesophageal
      echocardiography. METHODS: A retrospective analysis was made in 35 patients who
      underwent biventricular repair by one surgeon between November 1997 and January
      2004. All patients received intraoperative transesophageal echocardiography and
      follow-up transthoracic echocardiography at 19.1 +/- 18.02 months (range, 7 days
      to 5 years; median, 15.1 months). RESULTS: In left-sided atrioventricular valve
      regurgitation, 34.3% (12 of 35) of patients showed discrepancy during follow-up,
      and 28.6% (10 of 35) showed progression of regurgitation (from grade I to II). In
      right-sided atrioventricular valve, 11.4% (4 of 35) of patients showed
      discrepancy, 9.6% (3 of 35) showed progression of regurgitation (from grade I to
      II). CONCLUSIONS: In complete atrioventricular septal defects, intraoperative
      transesophageal echocardiography did not show the same findings as that of follow
      up transthoracic echocardiography in some cases. However, this discrepancy is not
      so great as to require reoperation in early to midterm follow-up. Therefore,
      intraoperative transesophageal echocardiography may be used as tool to predict
      durability of surgical results and to decrease the incidence of reoperation in
      complete atrioventricular septal defects.

PMID- 15975340
TI  - Invited commentary.

PMID- 15975341
TI  - Acute sleep deprivation in the thoracic surgical resident does not affect
      operative outcomes.
AB  - BACKGROUND: There is an increasing trend toward work hour restrictions for
      doctors world wide. These reforms have been inspired, in part, by the assertion
      by some that the fatigued physician is more prone to making errors.
      Interestingly, there is very little in the way of objective data with regard to
      the effects of sleep deprivation on patient outcomes. We have recently studied
      this in attending surgeons. The present study focused on thoracic surgical
      residents. Our hypothesis was that acute sleep deprivation would not lead to an
      increase in operative times or complications. METHODS: A retrospective review of
      all cases performed by thoracic surgical residents at the University of Virginia
      from January 1994 to March of 2004 was done. Complication rates of cases
      performed by "sleep deprived" (SD) residents were compared with cases done when
      the residents were "not sleep deprived" (NSD). A resident was deemed sleep
      deprived if he or she performed a case the previous evening that started between
      10 pm and 5 am or ended between the hours of 11 pm and 7:30 am. RESULTS: A total
      of 7,323 cases were recorded in the STS database over the 10-year period
      examined. Two hundred and twenty-nine of these cases (3%) were performed by SD
      residents. Mortality rates for coronary artery bypass operations showed no
      significant differences (2.1% [SD = 3 of 141 patients] vs 3.1% (NSD = 143 of 4452
      patients), p = 0.63). A comparison of operative, neurologic, renal, infectious,
      and pulmonary complications as well as cardiopulmonary bypass times, cross-clamp
      times, the use of blood products, and length of stay also demonstrated no
      significant differences between groups. CONCLUSIONS: Acute sleep deprivation in
      thoracic surgical residents does not affect operative efficiency, morbidity, or
      mortality in cardiac surgical operations.

PMID- 15975342
TI  - Recombinant factor VIIa in the treatment of postoperative hemorrhage after
      cardiac surgery.
AB  - BACKGROUND: A generalized coagulation disorder after cardiac surgery that is
      associated with massive postoperative hemorrhage is not completely understood.
      Recombinant factor VIIa (rFVIIa) has emerged as a possible "salvage" medication.
      Limited experience reported in the literature and fears of possible
      thromboembolic complications make the use of rFVIIa in the treatment of bleeding
      after cardiac surgery controversial. METHODS: We analyzed retrospectively all
      consecutive cardiac surgical patients who have received rFVIIa in the Helsinki
      University Hospital in order to evaluate the safety and efficacy of rFVIIa after
      cardiac surgery in our institution. Altogether, 16 patients were identified from
      operating room and intensive care unit (ICU) databases. Patient records and
      operating room and ICU databases were reviewed. RESULTS: In this series of high
      risk patients hospital mortality was high (25%). A definite hemostatic effect was
      seen after rFVIIa administration in all but three patients (82%). Mean amount of
      bleeding and amount of platelet and fresh frozen plasma transfusions decreased
      significantly after rFVIIa administration. Four patients had serious
      postoperative thromboembolic complications. CONCLUSIONS: Recombinant factor VIIa
      was effective in restoring hemostasis, but thromboembolic complications occurred
      after rFVIIa use. They may be related to the underlying pathologies and surgery
      performed. It is possible, however, that rFVIIa treatment contributed to their
      occurrence.

PMID- 15975343
TI  - Surgical results of acute aortic dissection complicated with cerebral
      malperfusion.
AB  - BACKGROUND: In patients with acute type A aortic dissection complicated by
      cerebral malperfusion, the surgical treatment remains challenging. This
      retrospective study reports the results of surgical interventions and the
      clinical features of these patients. METHODS: From 1999 to 2004, 63 patients
      underwent surgical treatment for acute type A aortic dissection. Sixteen patients
      (25.3%) showed preoperative newly developed neurologic deficits (cerebral
      malperfusion). In patients with cerebral malperfusion, the characteristics,
      neurologic symptoms, computed tomography findings, interval from onset to
      operation, and operative details (procedure, arterial cannulation site, method of
      brain protection) were reviewed. RESULTS: The hospital mortality rate was 43.7%
      (7 of 16 patients) for the cerebral malperfusion group and 17.0% (8 of 47
      patients) for the noncerebral malperfusion group (all patients, 23.8%).
      Multivariate analysis showed preoperative cerebral malperfusion as the sole risk
      factor for hospital mortality. Six patients, including all patients in a
      preoperative coma, died of severe brain damage within 1 month after surgery. Most
      patients were diagnosed with right hemispheric cerebral infarction by
      postoperative brain computed tomography. The operative details and the time
      interval from onset to operation were not significant predictors of death. The
      cumulative survival rate at 4 years was 75.5% in patients without cerebral
      malperfusion and 50.1% with cerebral malperfusion (p = 0.091). CONCLUSIONS: The
      results of surgical treatment for acute type A dissection complicated with
      cerebral malperfusion demonstrated high hospital mortality, but the long-term
      survival was similar to patients without cerebral malperfusion, with an
      acceptable neurologic outcome, excluding preoperative coma patients. Appropriate
      protection of ischemic brain tissue should be implemented to improve the surgical
      results in these patients.

PMID- 15975344
TI  - Axillary artery cannulation improves operative results for acute type a aortic
      dissection.
AB  - BACKGROUND: This study was undertaken to identify preoperative and postoperative
      predictors of hospital death of patients with acute type A aortic dissection.
      METHODS: Between May 1,1992, and July 31, 2004, 106 consecutive patients (59 male
      and 47 female, mean age 62.2 +/- 12.1 years) with acute type A aortic dissection
      underwent surgery with open technique and cerebral protection by antegrade
      selective cerebral perfusion. The external iliac artery or femoral artery alone
      was used for arterial cannulation in 37 patients; however, the right axillary
      artery was cannulated in 69 patients. Univariate analysis of potential risk
      factors was performed to identify risk factors for hospital death and was
      followed by multivariate analysis by a stepwise logistic regression model to
      identify independent risk factors. RESULTS: Sixteen patients died
      postoperatively, and the overall hospital mortality rate was 15.1%. Univariate
      analysis revealed shock (p = 0.020), visceral ischemia (p = 0.007), root
      replacement (p = 0.041), and absence of axillary artery perfusion (p = 0.003) as
      significant risk factors for hospital death. Multivariate analysis revealed
      visceral ischemia (p = 0.0028, odds ratio 18.4) and absence of axillary artery
      perfusion (p = 0.0014, odds ratio 8.2) as independent preoperative and
      intraoperative predictors of hospital death. CONCLUSIONS: Achievement of greater
      success in the surgical treatment of acute type A dissection will require
      axillary artery cannulation and measures to prevent visceral malperfusion.

PMID- 15975345
TI  - Femoral versus aortic cannulation for surgery of chronic ascending aortic
      aneurysm.
AB  - BACKGROUND: Femoral artery cannulation and retrograde arterial perfusion have
      been postulated to increase the risk of cerebral embolism. In this study, the
      impact of the arterial cannulation site on the perioperative results after
      proximal aortic surgery is evaluated. METHODS: Between January 1996 and December
      2002, a total of 327 patients underwent proximal aortic repair for chronic non
      dissected aortic disease. The arterial inflow was established by cannulation of
      the aortic arch (group A) or the femoral artery (group F) in 166 and 161
      patients, respectively. RESULTS: The early 30-day mortality was 0.9% (3 patients
      [1 patient in group A and 2 patients in group F]). The overall rate of early
      focal neurologic dysfunction (permanent and transient) was 4% (13 patients) and
      there was no significant difference between the two groups (4.2% vs 3.7%). Due to
      an intraoperative injury of the arterial wall, there were 6 repairs (3.6%) of the
      aortic arch in group A and 1 repair (0.6%) of the femoral artery in group F. The
      univariable examination of preoperative and intraoperative variables demonstrated
      that hypertension and increased cholesterol level could be possible independent
      risk factors for neurologic morbidity. In the following stepwise logistic
      regression, only the preoperative hypercholesterolemia was identified as an
      independent predictor for postoperative focal neurologic dysfunction.
      CONCLUSIONS: The arterial inflow via the femoral artery and the subsequent
      retrograde perfusion during cardiopulmonary bypass do not increase the risk of
      neurologic complications in patients who undergo proximal aortic repair due to
      chronic non-dissected aortic aneurysm. Because there is an increased risk of
      aortic wall injury during cannulation, the femoral artery seems to be more
      suitable in these cases for cannulation than the proximal aorta.

PMID- 15975346
TI  - Invited commentary.

PMID- 15975347
TI  - Aortic arch replacement using a trifurcated graft: simple, versatile, and safe.
AB  - BACKGROUND: Hypothermic selective antegrade cerebral perfusion during aortic arch
      replacement may prevent adverse neurologic sequelae. It can be provided via
      balloon-tipped catheters or a branched graft sewn to the brachiocephalic vessels.
      We report a consecutive series of total arch replacement using a trifurcated
      graft. METHODS: From September 1999 through October 2004, 109 patients underwent
      nonemergent total arch replacement using this technique. The graft, placed during
      a period of hypothermic circulatory arrest, was used for selective cerebral
      perfusion during the arch reconstruction. RESULTS: Adverse outcomes were seen in
      9 (8.3%) patients: hospital death in 5 (4.6%), and stroke in 5 (4.6%). Transient
      neurologic dysfunction was noted in 6 (5.5%) patients. Mean duration of
      hypothermic circulatory arrest was 31.2 +/- 6.6 minutes and selective cerebral
      perfusion was 65.3 +/- 20.9 minutes. Reoperation for bleeding was required in 3
      (2.8%) patients and prolonged intubation in 15 (13.8%). Median intensive care
      unit stay was 3 days (interquartile range 2-4; range, 1 to 108) and hospital stay
      was 9 (interquartile range 8-15; range, 5 to 108). CONCLUSIONS: The trifurcated
      graft technique results in low rates of perioperative mortality, temporary
      neurologic dysfunction, and stroke. It may reduce cerebral embolization as it
      requires no instrumentation of the aortic arch to establish selective cerebral
      perfusion and, although it mandates hypothermic circulatory arrest to place the
      graft, this interval is reliably brief enough to fall within accepted safe
      limits. This strategy leaves no residual arch tissue behind, and allows placement
      of an elephant trunk proximal to one or more arch vessels if anatomically
      indicated.

PMID- 15975348
TI  - Midterm results of surgical treatment of thoracic aortic disease in dialysis
      patients.
AB  - BACKGROUND: We investigated the influence of dialysis on late aortic events in
      end-stage renal failure patients who had undergone replacement of the thoracic
      aorta. METHODS: Between 1990 and 2003, 28 dialysis patients underwent thoracic
      aortic aneurysm repair. The cause was non-dissection in 17 patients and
      dissection in 11 patients. Six patients needed emergency operations. After the
      initial operation, 10 patients in the dialysis group had a patent false channel
      distal to the operative area, and 7 patients in the dialysis group had untreated
      separate aneurysms. These lesions were defined as residual aneurysms. We
      performed a retrospective case-control analysis of survival and late aortic
      events (enlargement of the remaining thoracic aorta, sudden death and
      reoperation) in dialysis patients versus carefully matched non-dialysis patients.
      Matching criteria included age, sex, cause, operative procedures, operative date,
      and operative status (elective or emergency). RESULTS: Survival rates at 1 and 5
      years for dialysis patients versus non-dialysis patients were 63 +/- 9% vs. 85 +/
      7% and 41 +/- 11% versus 64 +/- 13%, respectively (p = 0.02). Four of nine late
      deaths in the dialysis group were due to rupture of residual aneurysm. Freedom
      from late aortic events for dialysis patients versus non-dialysis patients was
      91+/- 6% versus 92 +/- 5% and 25 +/- 14% versus 68 +/- 12% at 1 and 5 years,
      respectively (p = 0.0073). CONCLUSIONS: There is a high incidence of late aortic
      events in dialysis patients undergoing thoracic aortic aneurysm repair. This
      finding indicates the need for close follow-up examination of dialysis patients
      who have undergone surgical treatment of thoracic aortic disease.

PMID- 15975349
TI  - Annuloaortic ectasia and giant cell arteritis.
AB  - BACKGROUND: Thoracic aortic aneurysm, aortic dissection and aortic valve
      regurgitation have been widely described in patients with Horton disease, also
      known as giant cell arteritis. We present our midterm experience with patients
      with these features. METHODS: A total of 386 cases of ascending aorta and aortic
      valve replacement performed for thoracic aortic aneurysm and aortic insufficiency
      between 1998 and 2004 were reviewed. Among them 10 cases of histopathologically
      confirmed GAA were identified. Patients were predominantly female (90%); the mean
      age was 74.5 +/- 4.6 years. RESULTS: Eight patients (80%) showed typical
      annuloaortic ectasia, leading to significant aortic valve regurgitation. These
      subjects underwent a Bentall operation. Two patients whose sinuses seemed
      undilated and macroscopically normal had separate valve graft replacement at
      first operation and underwent reoperation due to dilatation of the native
      sinuses. Eight patients had partial aortic arch replacement (hemiarch), and 1
      underwent total arch replacement. Six-year survival was 0.9 +/- 0.09; freedom
      from reoperation at 6 years was 0.77 +/- 0.13. CONCLUSIONS: Annuloaortic ectasia
      is a common finding in giant cell arteritis. In patients with Horton disease, the
      aortic root should always be replaced regardless of macroscopic findings.

PMID- 15975350
TI  - The threat of adhesive embolization: BioGlue leaks through needle holes in aortic
      tissue and prosthetic grafts.
AB  - BACKGROUND: BioGlue Surgical Adhesive (CryoLife, Inc, Kennesaw, GA) is used to
      reinforce anastomoses during cardiovascular operations. Previous reports have
      raised concerns that adhesives may leak through suture-line needle holes and that
      resulting intraluminal glue may embolize. The purpose of this study was to
      determine if BioGlue leaks through anastomotic needle holes in aortic tissue and
      two common prosthetic graft materials. METHODS: Polypropylene suture was used to
      create end-to-end anastomoses in gelatin-sealed woven polyester grafts (n = 45),
      expanded polytetrafluoroethylene (ePTFE) grafts (n = 45), and fresh porcine
      aortas (n = 45). An additional 45 anastomoses were created in ePTFE grafts using
      ePTFE sutures. The outer surface of each anastomosis was covered with BioGlue.
      Anastomoses underwent inspection with direct magnification or histology. RESULTS:
      BioGlue leaked through needle holes and into the lumen in 10% of anastomoses (18
      of 180). Leaks were significantly more common in fresh aorta (10 of 45, 22%) than
      in prosthetic grafts (8 of 135, 6%; p = 0.003). Suture size did not significantly
      affect the incidence of leak. The use of ePTFE sutures did not eliminate BioGlue
      leakage. Prosthetic graft leaks created discreet round adhesive particles. In
      contrast, aortic tissue leaks resulted in thin, friable flakes of glue extending
      along the intimal surface. Aortic histology confirmed that BioGlue reached the
      vessel lumen via the suture channels. CONCLUSIONS: BioGlue leaked through the
      needle holes in fresh aortic tissue and prosthetic grafts. Intraluminal adhesive
      particles were easily dislodged, supporting concerns regarding embolization. The
      potential for adhesive embolization should be a factor when considering the
      relative risks and benefits of using BioGlue.

PMID- 15975351
TI  - Impact of complete revascularization on long-term survival after coronary artery
      bypass grafting in octogenarians.
AB  - BACKGROUND: Complete revascularization is important in young patients undergoing
      coronary artery bypass grafting, but this principle remains less absolute in
      elderly patients. The purpose of this study was to determine how complete
      revascularization influenced long-term survival after coronary artery bypass
      grafting in octogenarians. METHODS: From 1986 to 2003, 500 consecutive patients
      80 to 94 years of age underwent coronary artery bypass grafting. Complete
      revascularization was defined as placement of at least one graft to each of the
      three major vascular regions that included a 50% diameter lesion.
      Revascularization was complete in 400 (80%) patients and incomplete in 100 (20%)
      patients. Mean (+/- standard deviation) follow-up was 51 +/- 41 months and was
      99% complete (2,102 total patient-years). RESULTS: Operative mortality was 8% +/-
      2% (+/-95% confidence interval) and was statistically lower with complete (7% +/-
      3%) versus incomplete (13% +/- 7%) revascularization (p < 0.05). Of 459 operative
      survivors, there were 261 late deaths. Multivariate regression analysis
      identified six independent predictors of late death: earlier operative year, male
      sex, peripheral or cerebrovascular disease, congestive heart failure, and
      incomplete revascularization (p < 0.03 for all). Excluding operative deaths, mean
      survival (Kaplan-Meier) was 82 months with complete revascularization compared
      with 65 months with incomplete revascularization (p < 0.008). Survival was 62% +/
      3% with complete versus 45% +/- 6% with incomplete revascularization at 5 years
      and 39% +/- 3% with complete versus 25% +/- 6% with incomplete revascularization
      at 8 years (p < 0.008). CONCLUSIONS: In octogenarians undergoing coronary artery
      bypass grafting, complete revascularization correlated with improved long-term
      survival, increasing mean survival by almost 25% compared with incomplete
      revascularization.

PMID- 15975352
TI  - Skeletonized gastroepiploic artery as a composite graft for total arterial
      revascularization.
AB  - BACKGROUND: Despite the purported advantages of using a gastroepiploic artery
      graft during coronary artery bypass, insufficient potential flow capacity and
      vasospasm remain major concerns. We assessed the efficacy and results of using a
      skeletonized composite gastroepiploic artery graft in situations in which
      bilateral internal thoracic and radial arteries could not be used. METHODS:
      Between January 2000 and August 2002, 37 patients (25 men, 12 women; mean age,
      59.9 years) underwent grafting with composite grafts using a skeletonized left
      internal thoracic artery plus the gastroepiploic artery. Coronary angiograms were
      performed in the immediate (median, 14 days, 36 patients) and early (median, 348
      days, 32 patients) postoperative periods. Off-pump coronary artery bypass
      grafting was performed in all but 2 patients. RESULTS: There were no deaths. The
      respective postoperative patencies of the left internal thoracic artery and
      gastroepiploic artery were 36 of 37 (97.2%) and 73 of 75 (97.3%) at the immediate
      period, and 34 of 34 and 62 of 67 (92.5%) at the early period. During follow-up,
      only 1 patient required percutaneous intracoronary intervention for
      gastroepiploic artery occlusion. CONCLUSIONS: Skeletonized composite
      gastroepiploic artery grafts showed satisfactory clinical and angiographic
      results in situations in which bilateral internal thoracic and radial arteries
      could not be used. Although it needs longer follow-up, these early results
      demonstrated that the gastroepiploic artery may be a useful option in some
      situations of total arterial revascularization, used either as an in situ or as a
      composite graft.

PMID- 15975353
TI  - Flow capacity of gastroepiploic artery versus vein grafts for intermediate
      coronary artery stenosis.
AB  - BACKGROUND: Native flow competition is a significant factor affecting bypass
      graft patency. The objective of this study was to compare the effect of
      competitive flow on conduit flow dynamics in the gastroepiploic artery (GEA) and
      the saphenous vein graft (SVG). METHODS: In 51 patents, 23 GEAs (in-situ grafts)
      and 28 SVGs (aortocoronary grafts) were examined using a Doppler-tipped guidewire
      during coronary angiography after coronary artery bypass. Graft flow volume at
      rest and maximum graft flow volume during hyperemia were calculated from graft
      diameter and average peak velocity at rest and maximum average peak velocity
      induced by papaverine hydrochloride injection. Grafts were classified according
      to the grade of native coronary artery stenosis; group S (14 GEAs and 16 SVGs)
      displayed over 75% stenosis and group M (9 GEAs and 12 SVGs) exhibited over 50%
      up to 75% stenosis. RESULTS: In group S, no difference in flow volume was
      apparent between the GEA and the SVG at rest (36+/- 17 vs 42 +/- 16) and during
      hyperemia (78 +/- 30 vs 88 +/- 28). In group M, flow volume of the GEA was
      significantly lower than that of the SVG at rest (17 +/- 11 vs 38 +/- 12; p =
      0.029) and during hyperemia (32 +/- 19 vs 94 +/- 46; p = 0.001). CONCLUSIONS:
      These data suggest that in intermediate coronary stenosis, GEA flow is
      compromised by native flow competition, whereas the SVG flow dynamics is
      maintained. However, the GEA can provide comparable flow capacity to the SVG and
      will achieve good surgical results when target coronary artery selection is
      appropriate.

PMID- 15975354
TI  - Using the EuroSCORE to assess changes in the risk profiles of the patients
      undergoing coronary artery bypass grafting before and after the introduction of
      less invasive coronary surgery.
AB  - BACKGROUND: Patients undergoing coronary artery bypass grafting seem to be older
      and have more comorbidity than patients in prior decades. We retrospectively
      assessed changes in the predicted mortality risk of patients who underwent
      coronary artery bypass surgery before and after the introduction of minimally
      invasive surgical techniques. METHODS: Between 1993 and 2002, 345 consecutive
      patients underwent coronary bypass surgery at Osaka Prefectural General Hospital.
      Minimally invasive direct coronary artery bypass was introduced in 1997 and off
      pump bypass in 1999. Patients were divided into two groups, based on the year of
      surgery (1993 to 1996 and 1997 to 2002), and mortality risk was assessed with the
      European System for Cardiac Operative Risk Evaluation (EuroSCORE). RESULTS: The
      in-hospital mortality was 3% overall (11 of 345), 8% during the early period (6
      of 106), and 2% during the later period (5 of 239). Multiple regression analysis
      identified an emergent operation to be an independent predictor of in-hospital
      mortality (p = 0.035). Factors associated with higher scores were recent
      myocardial infarction (p = 0. 028), preoperative intraaortic balloon pumping (p =
      0.026) and preoperative ventilation (p = 0.026), but not age. Scores were higher
      in the minimally invasive (6.5 +/- 3.6, p = 0.004) and off-pump (5.0 +/- 3.7, p =
      0.04) groups than in the conventional bypass group (4.1 +/- 3.3). The arterial
      graft in coronary artery bypass graft group was significantly less than in off
      pump coronary artery bypass group (0.8 +/- 0.8 vs 1.2 +/- 0.8, p = 0.0001).
      Despite the increasing risk scores, overall in-hospital mortality decreased.
      CONCLUSIONS: The EuroSCORE was useful for assessing changes in the risk profile
      of patients undergoing bypass surgery over the past decade. The decrease in in
      hospital mortality despite the increased risk might reflect the introduction of
      less invasive coronary surgery in high-risk patients.

PMID- 15975355
TI  - On-pump versus off-pump surgical revascularization for left main stem stenosis:
      risk adjusted outcomes.
AB  - BACKGROUND: Recent publications have shown coronary surgery is safe and effective
      in patients with critical left main stem stenosis when using off-pump coronary
      surgery techniques. However, these studies were small and did not adjust for
      differences in case mix. METHODS: Between April 1997 and March 2003, 1,197
      consecutive patients with critical left main stem stenosis (> 50%) underwent
      coronary surgery. Two hundred and fifty-nine (21.6%) of these patients had off
      pump coronary surgery, while 938 (78.4%) received on-pump coronary surgery.
      Multivariate logistic regression and Cox proportional hazards analysis were used
      to assess the effect of off-pump coronary surgery on outcomes, while adjusting
      for patient characteristics (treatment selection bias). Treatment selection bias
      was controlled by constructing a propensity score from core patient
      characteristics. The propensity score was the probability of receiving off-pump
      coronary surgery and was included along with the comparison variable in the
      multivariable analyses of outcome. RESULTS: After adjusting for the propensity
      score, the requirement for inotropic support (22.4% versus 35.3%; p < 0.001) or a
      prolonged length of stay (5.3% versus 9.3%; p = 0.034) were significantly reduced
      after receiving off-pump coronary surgery. There was a trend to suggest that off
      pump patients had a lower incidence of stroke and chest infection. The adjusted
      freedom from death in off-pump patients at 2 years was 94.6% compared with 93.6%
      for on-pump patients (p = 0.54). CONCLUSIONS: After risk adjustment, patients
      with critical left main stem stenosis can undergo off-pump coronary surgery
      safely, with results comparable with on-pump coronary surgery.

PMID- 15975356
TI  - Invited commentary.

PMID- 15975357
TI  - Off-pump coronary artery bypass grafting using only arterial grafts in elderly
      patients.
AB  - BACKGROUND: This study aimed to elucidate the safety and feasibility of off-pump
      coronary artery bypass grafting with only arterial grafts for elderly patients.
      METHODS: Of 653 patients who underwent off-pump coronary artery bypass grafting
      from April 2000 to December 2003, 581 patients did so with only arterial grafts.
      The average age was 66.9 +/- 9.3 years. The patients were divided into the elder
      group E (75 years old or more: 111 cases) or the younger group Y (younger than 75
      years old: 470 cases). The mean follow-up term was 21 +/- 12 months. RESULTS:
      Additive and logistic EuroSCOREs of group E were significantly higher than those
      of group Y (p < 0.0001). The number of bypass grafts was 3.3 +/- 0.9 in group E
      and 3.3 +/- 1.1 in group Y (p = 0.43). The proportion of total revascularization
      was 74% (82 of 111) in group E and 80% (377 of 470) in group Y (p = 0.15). The
      number of bilateral implementations of internal thoracic artery was 10 (9.0%) in
      group E and 196 (42%) in group Y (p < 0.0001). The graft patency rate was 98.7%
      in group E and 97.8% in group Y (p = 0.96). Hospital mortality was 2.7% (3 of
      111) in group E and 0.2% (1 of 470) in group Y (p = 0.095). The causes of death
      were unrelated to cardiac events. Major adverse cardiac events occurred in 5
      patients (5.1%) in group E and in 24 patients (5.6%) in group Y (p > 0.99).
      CONCLUSIONS: Off-pump coronary artery bypass grafting using only arterial grafts
      in elderly patients is as safe and feasible as in young patients.

PMID- 15975358
TI  - Comparison of two strategies for the management of antiplatelet therapy during
      urgent surgery.
AB  - BACKGROUND: The optimal management of aspirin and clopidogrel therapy before
      surgery in patients with acute coronary syndrome is uncertain. Aspirin and
      clopidogrel within 5 days of surgery increases postoperative bleeding and
      reexploration. However, in acute coronary syndrome patients the risk of bleeding
      must be balanced against the risks of discontinuing the treatment and delaying
      surgery. METHODS: From June 2002 to July 2003, patients undergoing urgent
      coronary artery bypass graft surgery (CABG) for acute coronary syndrome were
      randomly assigned to one of two groups. The treatment group remained on aspirin
      and clopidogrel therapy till surgery, receiving intraoperative aprotinin. The
      placebo group received placebo for 5 days before surgery and received placebo
      infusions intraoperatively. Platelet reactivity in response to adenosine
      diphosphate was assessed by whole blood single-platelet counting. Of the 88
      patients eligible, 50 entered the study. RESULTS: Postoperative blood loss was
      significantly greater in the placebo group than in the treatment group (702 +/-
      120 mL versus 446 +/- 62 mL, p = 0.004). This difference was observed as early as
      8 hours postoperatively (385 +/- 66 mL versus 266 +/- 36 mL, p = 0.03). Patients
      in the placebo group also required more blood transfusions (1 +/- 0.3 units
      versus 0.3 +/- 0.2 units, p = 0.03). Three patients in each group underwent
      surgical reexploration for bleeding. CONCLUSIONS: The strategy of continuing
      aspirin and clopidogrel therapy with intraoperative aprotinin reduces
      postoperative blood loss, transfusion requirements, prevents delay to surgical
      treatment, and may prevent major adverse cardiac events before surgery.

PMID- 15975359
TI  - Transmural differences in myocardial function and metabolism during direct left
      ventricular to coronary artery sourcing.
AB  - BACKGROUND: We investigated the hypothesis that in the absence of collateral
      circulation, a left ventricle-coronary artery (LV-CA) bypass will maintain normal
      LV wall function and metabolism transmurally, both at rest and during stress,
      when the left anterior descending coronary artery (LAD) is acutely occluded
      proximally. METHODS: In 18 anesthetized pigs (74 +/- 7 kg, mean +/- standard
      deviation), a covered stent was placed transmurally in the lateral wall of the
      beating LV and connected to the proximal LAD via an arterial graft. Subepicardial
      and subendocardial segmental shortening as well as interstitial lactate and
      glucose concentrations were measured regionally by sonomicrometry and
      microdialysis, respectively. RESULTS: When the LAD was occluded proximally,
      direct left ventricular sourcing decreased the net LAD flow to 64 +/- 25% of the
      native flow (n = 18, all animals). In the subepicardium, systolic shortening (SS)
      decreased to 87 +/- 18% of baseline (p = 0.124), with the appearance of minor
      postsystolic shortening (PSS), and minor changes in interstitial lactate and
      glucose levels. In the subendocardium, in contrast, SS decreased to 54 +/- 20% (p
      = 0.001). Marked PSS concurred with a sixfold increase in lactate (p = 0.008),
      and a 65 +/- 31% decrease in glucose (p = 0.003), indicating subendocardial
      anaerobic metabolism. Stress induced by infusion of dobutamine increased lactate
      and decreased glucose concentration in the subepicardium to subendocardial
      levels, indicating transmural anaerobic metabolism. CONCLUSIONS: In the
      anesthetized pig, direct sourcing by a LV-CA bypass distal to an acute coronary
      occlusion resulted in a 36% decrease in net forward coronary flow, subendocardial
      anaerobic metabolism, and loss of subendocardial contractile function at rest.
      These adverse effects extended into the subepicardium when the heart was
      stressed.

PMID- 15975360
TI  - Invited commentary.

PMID- 15975361
TI  - Effect of the left internal mammary artery to the left anterior descending artery
      on mortality and morbidity after combined coronary and valve operations.
AB  - BACKGROUND: The effect of using the left internal mammary artery in combined
      coronary and valve operations have not been fully investigated. We aimed to
      quantify the impact of the left internal mammary artery to the left anterior
      descending artery on early and mid-term outcomes in these patients. METHODS: Data
      was collected prospectively on 630 consecutive patients who underwent
      revascularization of the left anterior descending artery with concomitant valve
      operations between April 1997 and March 2003. Multivariate logistic regression
      and Cox proportional hazards analyses were used to adjust in-hospital outcomes
      and Kaplan-Meier survival curves. A propensity score for left internal mammary
      artery use was constructed to control for selection bias. RESULTS: The left
      internal mammary artery was used in 478 (75.9%) patients. Univariate analyses
      found left internal mammary artery patients had significantly lower in-hospital
      mortality (6.3% versus 13.2%; p < 0.01) and postoperative renal failure (8.2%
      versus 13.8%; p = 0.038). After adjusting for treatment selection bias, in
      hospital mortality (adjusted odds ratio, 0.77; p = 0.45) and renal failure
      (adjusted odds ratio, 0.94; p = 0.86) were no longer significantly different. A
      total of 171 (27.1%) deaths occurred during the follow-up, with a total follow-up
      of 2,325 patient-years. The crude relative risk for the left internal mammary
      artery was 0.67 (p = 0.015). After adjusting for the propensity score, the
      adjusted relative risk was 0.91 (p = 0.62). CONCLUSIONS: The left internal
      mammary artery does not adversely affect the short-term and medium-term outcomes
      in patients undergoing concomitant coronary and valve operations. Survival at 7
      years was similar with or without the use of the left internal mammary artery.

PMID- 15975362
TI  - Ischemic mitral regurgitation: impact of the left ventricle and mitral valve in
      patients with left ventricular systolic dysfunction.
AB  - BACKGROUND: Mitral regurgitation (MR) is a common complication of ischemic heart
      disease, and its presence portends adverse outcomes. As the exact mechanisms of
      ischemic MR are not well defined, we characterized left ventricular global
      geometry, regional function, and regional myocardial scarring, in addition to
      mitral valve apparatus geometry, using magnetic resonance imaging (MRI) of
      ischemic heart disease patients with left ventricular dysfunction and varying
      degrees of ischemic MR. METHODS: Sixty patients with varying degrees of MR (none,
      mild, moderate, and severe) determined by echocardiography and referred for MRI
      assessment of ischemic heart disease were included. Left ventricular geometric,
      functional, and scar measurements in addition to mitral valve geometric
      measurements were evaluated. RESULTS: Clinical characteristics found to be
      significant predictors of degree of MR included severity of coronary artery
      disease (p < 0.05), completeness of myocardial perfusion (p < 0.005), and average
      systolic blood pressure (p < 0.05). Mitral systolic tenting area (p < 0.0001) in
      a statistical model with scarring of the anterior-lateral region (p < 0.05)
      proved to be the most powerful predictor of MR severity (r2 = 0.31). Mitral
      annular dilatation in the anterior-posterior direction (p < 0.0001) and
      diminished LV systolic function (p < 0.005) were important determinants of mitral
      systolic tenting area (r2 = 0.57). CONCLUSIONS: Mitral tenting in combination
      with regional left ventricular myocardial scarring are important mechanisms to
      the development of ischemic MR. Surgical annuloplasty addresses mitral tenting,
      but has little impact on the effect of regional scarring. Moderate-to-severe
      ischemic MR develops in patients with regional scarring of the anterior-lateral
      and inferior-posterior regions, and new surgical developments should take this
      into account.

PMID- 15975363
TI  - Prevention of systolic anterior motion after repair of the severely myxomatous
      mitral valve with an anterior leaflet valvuloplasty.
AB  - BACKGROUND: Systolic anterior motion after mitral valve repair of severely
      myxomatous valves is due to excess tissue or anterior displacement, or both, of
      the leaflet coaptation point. Our series of anterior leaflet valvuloplasty, an
      alternative to the sliding leaflet technique to prevent systolic anterior motion,
      is presented. METHODS: Between January 1, 1996 and January 6, 2003, we performed
      elliptical excisions of the base of the anterior leaflet in 47 patients with a
      mean age of 66 years (range, 29 to 86). All patients had an anterior leaflet
      height of 3.0 cm or more and an annular diameter of 4.0 cm or more. Repairs
      included posterior leaflet (37; 80%), and anterior leaflet (28; 61%) resections,
      with occasional transposition flaps (9; 19%). All 47 (100%) had an annuloplasty
      ring (9, Physio; 37, Seguin). Four (8%) included tricuspid repair, 6 (13%) aortic
      valve replacement, and 9 (19%) coronary artery bypass. Follow-up was between 2
      months and 8 years. RESULTS: There was no systolic anterior motion or in-hospital
      (30-day) mortality. Postoperative echocardiography revealed an average anterior
      leaflet height of 2.2 +/- 0.3 cm, with an annular diameter of 3 +/- 0.2 cm. The
      anterior/posterior leaflet ratio decreased from 1.6 +/- 0.2 to 1.4 +/- 0.1 cm
      while the coaptation point-annular plane distance decreased from 1.2 +/- 0.2 to
      0.9 +/- 0.1 cm. There were 4 late noncardiac deaths. Two patients have required
      mitral valve replacement owing to progressive disease and 6 patients were lost to
      follow-up. The 35 patients remaining have trace-mild mitral regurgitation.
      CONCLUSIONS: Our anterior mitral valve leaflet valvuloplasty, regardless of the
      ring, results in a decrease in surface area and excursion of the anterior leaflet
      without systolic anterior motion.

PMID- 15975364
TI  - Effect of training in mitral valve repair surgery on the early and late outcome.
AB  - BACKGROUND: Preservation of the native mitral valve provides important advantages
      over valve replacement. The aim of this study was to evaluate the effect of
      training for mitral valve repair on the outcome. METHODS: Between 1997 and 2004,
      471 patients underwent mitral valve repair procedures in a single firm. Of these
      procedures, 300 (64%) were performed by a consultant (TJS) (consultant group) and
      171 (36%) by trainees supervised by the same consultant (trainees group).
      RESULTS: Atrial fibrillation was more prevalent in the consultant group (p =
      0.02) but there were no significant differences in the demographics, etiology of
      mitral regurgitation, and other comorbidity between the groups. Posterior leaflet
      prolapse was more prevalent in the trainees group (p < 0.0001) and anterior
      leaflet prolapse (p < 0.0001), bileaflet prolapse (p = 0.003), and Barlow's
      syndrome (p = 0.0003) in the consultant group. The consultant performed a higher
      proportion of concomitant coronary artery bypass grafting (p = 0.04), aortic
      valve replacement (p = 0.02), procedures, and nonelective cases (p = 0.03) with
      shorter bypass (p = 0.01) and ischemic times (p = 0.0004) than trainees. The
      complication rate was similar in the two groups (26% vs 22%), but the consultant
      had a higher operative mortality than the trainees (5% vs 0.6%) (p = 0.01). A
      similar proportion in the two groups exhibited recurrent mitral regurgitation (8%
      vs 9%). Kaplan-Meier five-year freedom from reoperation (95.6 +/- 1.6 vs 95.7 +/-
      2.2%) (p = 0.7) and survival (82 +/- 4% vs 88 +/- 4%) (p = 0.09) were similar in
      the two groups. CONCLUSIONS: With appropriate patient selection, cardiothoracic
      trainees can be taught mitral valve repair surgery without a negative effect on
      the early or late outcome.

PMID- 15975365
TI  - Structural characterization of the chordae tendineae in native porcine mitral
      valves.
AB  - BACKGROUND: This study was aimed to characterize the different mitral valve
      chordae tendineae to provide additional understanding of their function. METHODS:
      Mitral valve chordae tendineae from fresh porcine hearts were stained for
      collagen and elastin using either a Verhoeff and van Gieson stain or Verhoeff
      light green stain. Cellular distribution was determined using a hematoxylin and
      eosin stain. Immunohistochemistry was used to verify the findings of vasculature.
      Biochemical assays were performed to quantify DNA, collagen, and elastin content
      of each of the six different types of chordae tendineae. RESULTS: Blood vessels
      were observed in the longitudinal and circumferential directions of the chordae.
      The strut chordae on the anterior leaflet of the mitral valve showed an increased
      degree of vascularization compared with the other chordae. All chordae had an
      inner layer characterized by a high concentration of collagen and an outer layer
      that was mostly elastin with interwoven collagen fibers. The collagen
      microstructure was characterized by directional crimping. Hematoxylin and eosin
      staining showed fibroblasts evenly distributed throughout the inner and outer
      layer of the chordae tendineae. Quantitative analysis showed significantly higher
      levels of DNA and collagen content in the anterior and posterior marginal chordae
      compared with the other chordae. CONCLUSIONS: The chordae tendineae were seen to
      have different microstructures according to chordal type. The presence of vessels
      characterized the chordae tendineae as complex living components that work in
      coordination with the papillary muscles and mitral valve leaflets to prevent
      mitral valve prolapse and regurgitation. They may also function to supply
      nutrients to the valve leaflets.

PMID- 15975366
TI  - Invited commentary.

PMID- 15975367
TI  - Midterm results after aortic valve replacement with a stentless bioprosthesis
      aortic valve.
AB  - BACKGROUND: It is suggested that a simplified implant model Cryolife-O'Brien
      (CryoLife International, Kennesaw, GA) offers less satisfactory outcome compared
      with standard stentless models. This study was conducted to prospectively
      evaluate the midterm results after aortic valve replacement with the Cryolife
      O'Brien stentless bioprosthesis. METHODS: In 1996, a prospective clinical trial
      using different stentless valves was initiated. From September 1996 through
      September 2002, 156 consecutive patients with a mean age of 74.5 years underwent
      aortic valve replacement with the Cryolife-O'Brien porcine stentless
      bioprosthesis. The predominant aortic valve lesion was stenosis in 128 and
      insufficiency in 28 cases. Patients have been followed from 2 to 72 months (mean,
      42 months). Echocardiography was performed by one echocardiographer
      preoperatively, intraoperatively, postoperatively at discharge, 2 to 6 months
      later, and annually thereafter. RESULTS: Sixty percent of patients received a
      valve 25 mm in diameter or larger; 39% had concomittant coronary bypass grafting.
      The 30-day operative mortality rate was 6.4%. Ten late nonvalve-related deaths
      have occurred. Severe aortic insufficiency caused by oversizing leads to early
      reoperation in 3 patients. The peak and mean systolic gradients decreased
      significantly during the first 12 months after implantation, p < 0.001, and the
      effective valve areas increased significantly during this time interval p <
      0.001. At 5 years, ten patients have moderate aortic insufficiency. The actuarial
      survival at 5 years was 88 +/- 3%. The rate for freedom from endocarditis was
      100% and for freedom from thromboembolic events was 94%. CONCLUSIONS: Midterm
      results after aortic valve replacement with the Cryolife-O'Brien stentless
      bioprosthesis are encouraging. Good hemodynamics have been coupled with low rate
      of valve-related complications, thus representing a very good alternative to
      conventional stented bioprostheses.

PMID- 15975368
TI  - Long-term results of the cloth-covered Starr-Edwards ball valve.
AB  - BACKGROUND: Between June 1968 and March 1977, Starr-Edwards cloth-covered ball
      valves were exclusively implanted, in a total of 74 patients at our institution,
      on a routine basis. METHODS: The retrospective postoperative follow-up rate was
      84.5%, for up to 36 years in mitral valve patients (982.5 patient-years); and
      81.3%, for up to 34 years in aortic valve patients (282.0 patient-years). Among
      66 operative survivors, 20 patients required reoperation due to valve-related
      complications. Mortality and morbidity after valve replacement was reviewed, and
      excised valves were examined. RESULTS: Survival rates after 10, 20, and 30 years
      were 74.6%, 64.1%, and 31.2%, respectively, after mitral valve replacement, and
      62.5%, 50.0%, and 43.8%, respectively, after aortic valve replacement. Freedom
      from all valve-related complications, respectively after 10, 20, and 30 years,
      was 70.5%, 55.9%, and 46.4% after mitral valve replacement, and 56.2%, 37.5%, and
      31.2% after aortic valve replacement. Cloth wear or pannus overgrowth was
      observed in all excised prostheses. Remarkable orifice tear was observed in
      mitral valves that were more than 20 years old. Pannus overgrowth on the studs
      contributed to prosthetic regurgitation in the older valves. Concomitant valve
      procedures were frequently required for valve-related complications or other
      aggravated valve lesions in the mitral position during the follow-up period.
      CONCLUSIONS: Early diagnosis of valve dysfunction and the decision to reoperate
      are important to improve the long-term results for surviving patients who have
      received a cloth-covered Starr-Edwards valve, especially in the mitral position.

PMID- 15975369
TI  - Intraoperative radiofrequency ablation for the treatment of atrial fibrillation
      during concomitant cardiac surgery.
AB  - BACKGROUND: Radiofrequency ablation has been recently introduced as an
      alternative to the surgical maze procedure to eliminate atrial fibrillation (AF).
      The purpose of this study was to examine the effectiveness of unipolar
      radiofrequency ablation in patients with AF undergoing open heart surgery.
      METHODS: A retrospective review was performed on 54 patients undergoing
      radiofrequency ablation with concomitant cardiac operations from March 2002
      through July 2003. Forty-two patients (77.8%) received left atrial ablation, and
      12 (22.2%) received biatrial ablation. RESULTS: Mean duration of preoperative AF
      was 46.3 +/- 44 months; 23 (42.6%) had AF 5 years or more, 32 (59.3%) had
      continuous AF, and 12 (22.6%) had a preoperative left atrial diameter of 6.0 cm
      or greater. At discharge, 33 patients (70.2%) were free from AF, 30 (62.5%) were
      in normal sinus rhythm, and 6 (12.7%) required a new pacemaker. Mid-term follow
      up was available in 44 (93.6%) patients, with a median follow-up of 8.7 months
      (range, 3 to 22 months). At follow-up, 34 (77.3%) patients were free from AF.
      There were no significant differences in freedom from AF in patients with
      continuous versus intermittent AF or duration of 5 or greater years versus less
      than 5 years. In patients with isolated mitral valve surgery and radiofrequency
      ablation, 22 (88.0%) were free from AF compared with 12 (63.2%) with other
      operations (p = 0.074). In patients with left atrial diameter less than 6.0 cm,
      30 (88.2%) were free from AF compared with 4 (40%) with left atrial diameter of
      6.0 cm or greater (p = 0.006). CONCLUSIONS: Radiofrequency ablation is an
      effective surgical option for the treatment of continuous or intermittent AF. The
      elimination of AF using radiofrequency ablation is most successful in patients
      undergoing isolated mitral valve surgery with preoperative left atrial diameter
      less than 6.0 cm.

PMID- 15975370
TI  - Beyond extended myectomy for hypertrophic cardiomyopathy: the resection-plication
      release (RPR) repair.
AB  - BACKGROUND: Extended myectomy for left ventricular outflow tract obstruction
      (LVOTO) due to hypertrophic cardiomyopathy (HCM) has good long-term results. In
      addition to the midseptal resection (R) for HCM, our group has introduced a novel
      variation in anterior leaflet plication (P) and release (R) of papillary muscle
      attachments. We sought to investigate the medium-term success of this three-step
      repair that addresses all aspects of complex HCM pathology. METHODS: Nineteen
      patients underwent resection-plication-release repair for complex HCM pathology.
      Transesophageal echocardiography was performed on all patients preoperatively and
      postoperatively to assess adequacy of resection, left ventricular outflow tract
      gradients, and mitral valve function. All patients underwent transthoracic
      outpatient echocardiography at a mean follow-up of 2.4 +/- 2.1 years (range, 0.5
      to 6). RESULTS: The average age of the patients was 57 +/- 14 years. The
      preoperative peak LVOTO was 137 +/- 45 mm Hg. The average degree of mitral
      regurgitation was 3.1. The average length of stay was 7.5 +/- 3.3 days. There
      were no readmissions or deaths in the group. Initial postoperative
      transesophageal echocardiography demonstrated marked reduction in LVOTO to 10 +/-
      17 mm Hg (p < 0.0001) and significant improvement in mitral regurgitation to 0.2
      (p < 0.0001). In follow-up, the LVOT gradient remained low at 6 +/- 14 (p >
      0.0001) and mitral regurgitation remained insignificant at 0.4 (p < 0.0001).
      CONCLUSIONS: Anterior leaflet plication and papillary muscle release are logical
      adjuncts to septal resection in the treatment of the complicated pathophysiology
      of obstructive HCM. Durable long-term results can be achieved with an aggressive
      approach to mitral valve pathology in conjunction with extended myectomy.

PMID- 15975371
TI  - Alternate waiting list strategies for heart transplantation maximize donor organ
      utilization.
AB  - BACKGROUND: Alternate waiting list strategies have been promoted as a means to
      offer the benefit of heart transplantation to a greater number of candidates. We
      undertook the current study to evaluate our experience with transplantation in
      alternate list (AL) candidates. METHODS: Adults undergoing heart transplantation
      from January 1, 2001, through April 15, 2004, were evaluated. Selected patients
      who did not meet criteria for standard listing for heart transplantation were
      offered alternate listing. Primary posttransplant outcomes included 30-day, 90
      day, and more than 90-day mortality, and determinants of perioperative morbidity.
      RESULTS: Thirty-seven patients (14.3%) met alternate list criteria. Among these
      alternate list patients, contraindications to standard listing included age
      greater than 65 years, amyloidosis, severe diabetes mellitus and peripheral
      vascular disease, human immunodeficiency virus, and high-risk retransplant. The
      average age of alternate list donors was 41.2 +/- 13.9 years. Survival analysis
      revealed no posttransplant survival advantage for standard list recipients
      However, mean ventilatory support time was significantly (p < 0.001) longer in
      the alternate list group (5.7 +/- 9.3 days) compared with the standard group (2.3
      +/- 4.2 days), and significantly more sternal wound infections (p = 0.03) were
      observed in the alternate list group (6 [16.2%]) compared with the standard group
      (13 [5.9%]). CONCLUSIONS: The alternate list patients demonstrated comparable
      survival with standard list patients, but did exhibit more ventilatory dependence
      and sternal wound infections. More than half of alternate list donor organs in
      the future could be considered for standard list candidates as well. Use of the
      alternate list reinforces the assertion that, even today, our donor criteria
      remain too stringent.

PMID- 15975373
TI  - Initial experience with a minimized extracorporeal bypass system: is there a
      clinical benefit?
AB  - BACKGROUND: Drawbacks of conventional cardiopulmonary bypass (CPB) are increased
      inflammatory response, deteriorated coagulation and systemic organ dysfunction. A
      closed extracorporeal circuit (CorX) features reduced foreign surface area and
      priming volume. Potential benefits were studied in comparing the CorX system with
      conventional CPB in arrested heart coronary artery bypass grafting (CABG).
      METHODS: Two hundred and four patients were randomly assigned either to CorX
      system (n = 101, group A) or a standard CPB with cardiotomy reservoir (n = 103,
      group B). Besides evaluation of perioperative data and routine blood samples, we
      focused on lung function and perioperative bleeding. Polymorphonuclear elastase
      (PMNE) and terminal complement complex (TCC) served to assess inflammatory
      response. RESULTS: Patient demographics and operative data did not differ between
      groups. Postoperative lung function was not significantly impaired comparing
      groups A and B. Intraoperative blood loss was significantly higher in group A
      compared with group B (1245 +/- 947 mL vs 313 +/- 282 mL, p < 0.0001) as well as
      the need of fresh frozen plasma. Postoperative chest drainage did not differ
      significantly between groups. Two patients in each group required re-exploration
      due to bleeding. One hour after CPB, PMNE as well as TCC were significantly lower
      in group A compared with group B (PMNE: 76 +/- 44 ng/mL vs 438 +/- 230 ng/mL, p <
      0.0001; TCC: 16 +/- 8 IU/mL vs 29 +/- 19 IU/mL, p < 0.0001). CONCLUSIONS: The
      CorX system is safe and feasible in patients undergoing CABG. Despite of markedly
      reduced inflammatory reaction, no clinical benefit was observed.

PMID- 15975372
TI  - Paracrine action enhances the effects of autologous mesenchymal stem cell
      transplantation on vascular regeneration in rat model of myocardial infarction.
AB  - BACKGROUND: There are several reports that engrafted mesenchymal stem cells
      (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains
      controversial. We hypothesize that transplantation of MSCs enhances vascular
      regeneration through a paracrine action. METHODS: A transmural myocardial
      infarction was created by ligation of the left anterior descending coronary
      artery in rats. Those with an ejection fraction less than 0.70 1 week after
      myocardial infarction were included. Autologous MSCs (1 x 10(7); 0.2 mL) or
      culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone
      (50 microL/injection at four sites; n = 20/group). At 2 weeks after
      transplantation, Western blot analysis was used to assay the paracrine factors
      and proapoptotic proteins. Echocardiography to assess heart function was
      performed on additional groups at 8 weeks after implantation. RESULTS: The
      angiogenic factors basic fibroblast growth factor, vascular endothelial growth
      factor, and stem cell homing factor (stromal cell-derived factor -1alpha)
      increased in the MSC-treated hearts compared with medium-treated hearts. This was
      accompanied by a downregulation of proapoptotic protein Bax in ischemic
      myocardium. Similarly, capillary density increased about 40% in MSC-treated
      hearts compared with medium-treated hearts (p = 0.001). Left ventricular
      contractility, indicated by fractional shortening, improved in MSC-treated hearts
      at 2 months after implantation (MSCs: 48.6% +/- 19.9%; medium: 18.7% +/- 6.4%; p
      = 0.004). CONCLUSIONS: Autologous MSC transplantation attenuates left ventricular
      remodeling and improves cardiac performance. The major mechanism appears to be
      paracrine action of the engrafted cells, increasing angiogenesis and
      cytoprotection.

PMID- 15975374
TI  - Invited commentary.

PMID- 15975375
TI  - Circulatory arrest and low-flow cardiopulmonary bypass alter CREB phosphorylation
      in piglet brain.
AB  - BACKGROUND: The purpose of this study was to determine the effects of low-flow
      cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest followed by
      postbypass recovery on the phosphorylation state of transcription factor, cyclic
      adenosine 3', 5'-monophosphate response element-binding protein (CREB), in the
      striatum of neonatal brain. METHODS: Neonatal piglets (1.4 to 2.5 kg)
      anesthetized with isoflurane and fentanyl were put on CPB. The animals were
      cooled to 18 degrees C during a 20-minute period. The CPB circuit flow was then
      either reduced to 20 mL.kg(-1).min(-1) for 90 minutes (low-flow CPB) or turned
      off for 90 minutes (deep hypothermic circulatory arrest), following with a
      gradual increase in the flow and rewarming during a 30-minute period and a 2-hour
      recovery. At the end of the recovery period, the animals were rapidly euthanized,
      and the striata were removed and frozen for immunochemical analysis by Western
      blot technique using antibodies against phosphorylated and total CREB. The
      results are presented as mean +/- standard deviation (p < 0.05 was significant).
      RESULTS: Deep hypothermic circulatory arrest did not result in alteration in
      either the level of CREB or its degree of phosphorylation in the piglet striatum
      whereas after low-flow CPB, CREB phosphorylation was significantly increased (p <
      0.005) and there was also an increase in CREB expression (p < 0.01). CONCLUSIONS:
      This study indicates that at 2 hours of recovery, low-flow CPB but not deep
      hypothermic circulatory arrest causes an increase in CREB phosphorylation and
      expression. Future studies will determine the degree to which the increase in
      CREB phosphorylation correlates with cell survival and neuronal injury after CPB.

PMID- 15975376
TI  - Platelet preservation with a glycoprotein IIb/IIIa inhibitor in a porcine
      cardiopulmonary bypass model.
AB  - BACKGROUND: We tested whether administration of FK633, a short-acting
      glycoprotein IIb/IIIa inhibitor, before median sternotomy and cardiopulmonary
      bypass was able to interrupt the platelet activation loop and thereby preserve
      platelet number and function. METHODS: This study investigated 16 pigs that
      underwent median sternotomy and 120 minutes of normothermic cardiopulmonary
      bypass (100 mL/kg) adding pericardial blood to the perfusate. FK633 was
      administered with heparin to one group (group F, n = 8), whereas only heparin was
      administered to the control group (group C, n = 8). Blood samples were obtained
      at several times, and complete blood count, platelet aggregation to adenosine
      diphosphate, thrombin-antithrombin complex, and bradykinin were evaluated. P
      selectin expression and fibrinogen binding on platelet surfaces were measured by
      flow cytometry. Template bleeding times were measured before and after
      cardiopulmonary bypass. Chest tube drainage and hematocrit were determined at 2
      and 6 hours after cardiopulmonary bypass. RESULTS: In group F, platelet counts
      were preserved from 90 minutes of cardiopulmonary bypass. Platelet aggregation
      was inhibited at the beginning of cardiopulmonary bypass and showed no change at
      wound closure, and bleeding times were shortened at 2 hours after cardiopulmonary
      bypass. There were significant reductions in hematocrit of drainage. Flow
      cytometry showed no changes in P-selectin expression and fibrinogen binding in
      group F, whereas P-selectin expression and fibrinogen binding were elevated in
      group C. CONCLUSIONS: Platelet inhibition with FK633 before invasive surgical
      procedure preserved platelet counts during and after cardiopulmonary bypass, and
      produced normal or near-normal bleeding times in the immediate postoperative
      period.

PMID- 15975377
TI  - Invited commentary.

PMID- 15975378
TI  - Tracheoplasty for expiratory collapse of central airways.
AB  - BACKGROUND: Severe central airway obstruction due to expiratory collapse occurs
      with malacia of intrathoracic trachea and main bronchi, often with chronic
      obstructive pulmonary disease. Bronchoscopically observed, it is confirmed by
      inspiratory-expiratory computerized tomographic chest scans. Prior attempts at
      surgical stabilization have not given dependable results. METHODS: Posterior
      tracheobronchial splinting with polypropylene mesh (Marlex) holds cartilages in
      more normal configuration, and fixes redundant membranous walls. Fourteen
      consecutive patients were so treated for severe dyspnea. Prior trials of various
      autologous and exogenous splints failed. RESULTS: All felt subjectively improved
      early, with decreased dyspnea, cough, and secretion retention, and with increased
      activities. Mean forced expiratory volume in 1 second rose from 51% predicted to
      73% (p = 0.009), and peak expiratory flow rate from 49% to 70% (p < 0.00001). One
      patient was lost to follow-up (1 year), 1 died of unrelated cause (5 years), 1
      died of chronic obstructive pulmonary disease (3 years), and 1 had decreased
      respiratory function over 5 years. Ten patients were available for long-term
      follow-up: 6 were judged to have an excellent result, 2 were good, and 2 were
      poor due to collapse of unsplinted main bronchi. CONCLUSIONS: Complete splinting
      of all malacic central airways with Marlex restores anatomic configuration and
      permanently prevents expiratory collapse, with relief of extreme dyspnea, cough,
      and secretion retention.

PMID- 15975379
TI  - Invited commentary.

PMID- 15975380
TI  - Morbidity, survival, and site of recurrence after mediastinal lymph-node
      dissection versus systematic sampling after complete resection for non-small cell
      lung cancer.
AB  - BACKGROUND: Mediastinal lymph-node dissection was compared to systematic
      mediastinal lymph-node sampling in patients undergoing complete resection for non
      small cell lung cancer with respect to morbidity, duration of chest tube drainage
      and hospitalization, survival, disease-free survival, and site of recurrence.
      METHODS: A consecutive series of one hundred patients with non-small-cell lung
      cancer, clinical stage T1-3 N0-1 after standardized staging, was divided into two
      groups of 50 patients each, according to the technique of intraoperative
      mediastinal lymph-node assessment (dissection versus sampling). Mediastinal lymph
      node dissection consisted of removal of all lymphatic tissues within defined
      anatomic landmarks of stations 2-4 and 7-9 on the right side, and stations 4-9 on
      the left side according to the classification of the American Thoracic Society.
      Systematic mediastinal lymph-node sampling consisted of harvesting of one or more
      representative lymph nodes from stations 2-4 and 7-9 on the right side, and
      stations 4-9 on the left side. RESULTS: All patients had complete resection. A
      mean follow-up time of 89 months was achieved in 92 patients. The two groups of
      patients were comparable with respect to age, gender, performance status, tumor
      stage, histology, extent of lung resection, and follow-up time. No significant
      difference was found between both groups regarding the duration of chest tube
      drainage, hospitalization, and morbidity. However, dissection required a longer
      operation time than sampling (179 +/- 38 min versus 149 +/- 37 min, p < 0.001).
      There was no significant difference in overall survival between the two groups;
      however, patients with stage I disease had a significantly longer disease-free
      survival after dissection than after sampling (60.2 +/- 7 versus 44.8 +/- 8
      months, p < 0.03). Local recurrence was significantly higher after sampling than
      after dissection in patients with stage I tumor (12.5% versus 45%, p = 0.02) and
      in patients with nodal tumor negative mediastinum (N0/N1 disease) (46% versus
      13%, p = 0.004). CONCLUSION: Our results suggest that mediastinal lymph-node
      dissection may provide a longer disease-free survival in stage I non-small cell
      lung cancer and, most importantly, a better local tumor control than mediastinal
      lymph-node sampling after complete resection for N0/N1 disease without leading to
      increased morbidity.

PMID- 15975381
TI  - Prognostic significance of carcinoembryonic antigen level in pleural lavage fluid
      for patients with lung adenocarcinoma.
AB  - BACKGROUND: Prognostic indicators for non-small cell lung cancer patients
      traditionally include TNM staging, pleural lavage cytology, and serum
      carcinoembryonic antigen levels. This prospective study evaluates
      carcinoembryonic antigen levels in pleural lavage fluid as a potential
      determinant for patients with lung adenocarcinoma. METHODS: One hundred and fifty
      patients underwent thoracotomy. Pleural lavage fluid was collected, and pleural
      lavage cytology and lavage carcinoembryonic antigen levels were determined. The
      control group included 40 patients with nonmalignant disease. RESULTS: Sixteen
      patients (10.7%) had positive pleural lavage cytologies. These patients and those
      with elevated serum carcinoembryonic antigen levels generally had a poor
      prognosis. Thirty-seven patients (24.7%), however, showed elevated lavage
      carcinoembryonic antigen levels, and a significant correlation with patient
      survival was demonstrated. Multivariate analysis confirmed these results. We also
      found a correlation between positive pleural lavage cytologies and serum
      carcinoembryonic antigen levels and patient survival in patients with pN0 disease
      but not in those with pN1-2 disease. Elevated lavage carcinoembryonic antigen
      levels, however, correlated significantly with survival rates in patients with
      pN1-2 disease. CONCLUSIONS: An elevated lavage carcinoembryonic antigen level is
      an independent prognostic determinant for patients with lung adenocarcinoma, even
      with advanced disease, and may be a more useful marker of subclinical
      microdissemination than pleural lavage cytology.

PMID- 15975382
TI  - Specialty training and mortality after esophageal cancer resection.
AB  - BACKGROUND: Surgeons with advanced training have lower mortality rates with some
      surgical procedures. The objective of the current study was to investigate the
      impact of thoracic surgery training on mortality rates of esophageal cancer
      resection. METHODS: We studied esophageal cancer resection in the national
      Medicare population during 1998 and 1999. Operative mortality rates (in-hospital
      or 30-day) were compared for thoracic surgeons and other surgeons, adjusting for
      patient characteristics, hospital volume, and surgeon volume. Surgeons with
      specialty training in thoracic surgery were those certified by the American Board
      of Thoracic Surgery. RESULTS: Of the 1,946 patients, 625 (32%) had their
      operation performed by a thoracic surgeon. After adjustment for patient
      characteristics, mortality rates were 37% (odds ratio, 1.37; 95% confidence
      interval, 1.02 to 1.82) higher for surgeons without specialty training compared
      with thoracic surgeons (adjusted mortality 16.5% versus 12.4%; p = 0.01).
      However, differences in mortality between high-volume and low-volume hospitals
      (24.3% versus 11.4%; p < 0.001) and surgeons (20.7% versus 10.7%; p < 0.001) were
      larger than those between thoracic and general surgeons. Although thoracic
      surgeons had lower mortality rates after adjusting for hospital volume, the
      effect of thoracic surgery training was no longer significant after accounting
      for surgeon volume (odds ratio, 1.23; 95% confidence interval, 0.92 to 1.63).
      CONCLUSIONS: Specialty training in thoracic surgery has an independent
      association with lower mortality after esophageal resection. But specialty
      training appears to be less important than hospital and surgeon volume.

PMID- 15975383
TI  - Open repair of paraesophageal hernia: reassessment of subjective and objective
      outcomes.
AB  - BACKGROUND: Surgical repair of paraesophageal hernias (PEH) remains a challenging
      operation. Increasing numbers of patients are undergoing laparoscopic repair.
      This series provides an up-to-date benchmark of the results of open repair of PEH
      to compare with current laparoscopic series. METHODS: All patients undergoing
      surgical repair of PEH by a single surgeon between April 1996 and November 2001
      were included. Follow-up included postoperative SF-36 survey and objective
      reassessment (barium swallow or endoscopy) at a mean of 29.8 months. RESULTS:
      Seventy-two consecutive patients (mean age, 68.7 years) presented with large PEH.
      Presenting symptoms included heartburn (60%), dysphagia (43%), chest pain (42%),
      anemia (39%), and dyspnea (32%). Surgical treatment involved transabdominal open
      repair including sac excision, crural closure (primary closure 98.6%), and
      antireflux procedure (Hill procedure, 96%; Nissen fundoplication, 4%). No patient
      required a Collis procedure. Postoperative assessment (subjective, 97%;
      objective, 88%) was prospective. Median operative length was 155 minutes. Median
      length of stay was 4.5 days (range, 3 to 12 days). Postoperative complications
      occurred in 17 of 72 patients (23.6%), but no patient sustained intraoperative or
      postoperative visceral injuries. In-hospital and 30-day mortality was zero.
      Heartburn and dysphagia symptom scores demonstrated significant improvement (p <
      0.001). Postoperative SF-36 scores demonstrated levels better than the general
      population (six of eight categories) and better than the age-matched population
      (eight of eight categories). Objective follow-up demonstrated recurrent hernias
      in 11 patients (18%). Most of these recurrences (73%) were less than 2-cm sliding
      hernias, and no patients required revisional surgery. CONCLUSIONS: The results of
      open repair of PEH have continued to evolve in the same time that has seen the
      introduction of laparoscopic PEH repairs. Results with the open approach in the
      modern era can provide excellent outcomes, which are comparable to and in some
      measures exceed those obtained with the laparoscopic approach.

PMID- 15975384
TI  - Alternative surgical approaches for apical neurinomas: a thoracoscopic approach.
AB  - BACKGROUND: Neural tumors at the thoracic apex present technical problems for
      surgeons because of their inaccessibility and postoperative neural complications.
      Although several approaches offering better accessibility have been proposed,
      none have become standard. METHODS: Between 1976 and 2004, 23 patients,
      histologically 20 neurilemmomas and three ganglioneuromas, underwent surgical
      intervention for apical neurinoma. Surgical approaches were in three groups: (1)
      open thoracotomy, 8 patients; (2) transcervical, 10 patients; and (3) video
      assisted thoracoscopy utilizing intracapsular enucleation to preserve important
      nerves and vessels, 5 patients. Perioperative variables and postoperative
      neurological complications were reviewed and compared among the groups. RESULTS:
      Operation time and t blood loss in the vessels group were significantly less than
      in the other groups. Multivariate analysis with the perioperative variables
      showed the transcervical approach to be an independent predictor for
      postoperative neurologic complications (p = 0.0029). All patients remain free
      from recurrence, even in the follow-up period for patients in the vessels group
      ranging from 6 to 60 months (average, 35 months). CONCLUSIONS: Video-assisted
      thoracoscopic intracapsular enucleation, when an apical neurinoma is benign and
      well-capsulated, is the optimal treatment to preserve nerve function. Careful
      follow-up to monitor for recurrence is necessary.

PMID- 15975385
TI  - Preemptive use of bivalirudin for urgent on-pump coronary artery bypass grafting
      in patients with potential heparin-induced thrombocytopenia.
AB  - PURPOSE: The use of heparin in patients with heparin-induced thrombocytopenia
      (HIT) may result in severe complications or death. The diagnosis of HIT is
      frequently uncertain, however. Alternative anticoagulants in at-risk patients
      undergoing cardiac surgery with cardiopulmonary bypass remain problematic. The
      novel short-acting, direct-thrombin inhibitor bivalirudin is the only alternative
      to heparin/protamine being used in elective non-HIT patients during CPB.
      DESCRIPTION: Four patients with severe thrombocytopenia after heparin exposure
      and suspected acute HIT underwent on-pump coronary artery bypass grafting surgery
      with preemptive use of bivalirudin. A continuous bivalirudin infusion was used
      during cardiopulmonary bypass, and activated clotting times were used to monitor
      anticoagulation. EVALUATION: Anticoagulation with bivalirudin during
      cardiopulmonary bypass was effective and uncomplicated. Duration of operation was
      not prolonged, and perioperative blood loss and transfusion rates were
      acceptable. Activated clotting times were helpful for monitoring anticoagulation
      in these patients. CONCLUSIONS: These data provide further evidence of the
      feasibility of bivalirudin for anticoagulation during on-pump coronary artery
      bypass graft surgery in urgent clinical situations.

PMID- 15975386
TI  - Invited commentary.

PMID- 15975387
TI  - Pericardial patch augmentation for reconstruction of incompetent bicuspid aortic
      valves.
AB  - PURPOSE: Reoperation rates after repair of bicuspid aortic valves are higher than
      for mitral valve reconstruction. Secondary changes and small coaptation surface
      render repair unreliable. Satisfactory results have been reported for patch
      augmentation for tricuspid aortic valves. We have applied this technique for the
      repair of bicuspid aortic valves. DESCRIPTION: Our technique retains the bicuspid
      morphology of the incompetent aortic valve. A strip of glutaraldehyde-fixed
      pericardium is sutured to the free edge of the fused leaflet. A large coaptation
      surface is created, and competence of the bicuspid valve is achieved. EVALUATION:
      Sixteen patients underwent reconstruction of their bicuspid aortic valves by
      pericardial patch augmentation. There were no intraoperative or postoperative
      deaths. The degree of aortic regurgitation was none to trivial for all patients
      at a mean follow-up of 3.1 +/- 3.4 months. Planimetric effective orifice areas
      ranged above 2 cm2. Mean aortic gradients were 8.2 +/- 4.8 mm Hg, and the mean
      height of coaptation surface was 14.7 +/- 2.1 mm. CONCLUSIONS: The pericardial
      patch augmentation technique increases coaptation surface, and thus provides
      reliable early competence of reconstructed bicuspid aortic valves.

PMID- 15975388
TI  - Invited commentary.

PMID- 15975389
TI  - Initial experience with the Abiomed AB5000 ventricular assist device system.
AB  - PURPOSE: We describe our initial experience with the Abiomed AB5000 ventricular
      assist device (VAD). DESCRIPTION: The Abiomed AB5000 VAD is a system recently
      approved by the Food and Drug Administration that consists of a fully automatic,
      vacuum-assisted console and a paracorporeal, pneumatically driven blood pump. The
      VAD is designed for short or intermediate term use. The console is designed to
      support the BVS5000 or AB5000 blood pumps. The cannulas and implantation are
      similar to the BVS5000 system. EVALUATION: Four cases are described in which two
      AB5000 systems were placed de novo and two were transitioned from previously
      placed BVS5000 units. Hemolysis was observed in 2 cases. The AB5000 VAD flows
      were generally 4.0 to 4.5 L/min, approximately 0.5 L/min less than the BVS5000.
      Echocardiography demonstrated high-velocity jets from the inflow cannula in the 2
      hemolysis cases. One patient died of multiorgan system failure while on support,
      2 were successfully weaned from support and transferred to long-term care
      facilities, and 1 was weaned from support and successfully discharged to home.
      CONCLUSIONS: The AB5000 VAD is a versatile paracorporeal pneumatic VAD that can
      be placed de novo or transitioned from a previously placed BVS5000 unit without
      the need for additional surgery. Lower outputs, high-velocity jets, and hemolysis
      were observed in 2 of 4 cases. Modifications in cannulas design and placement as
      well as console reconfigurations may be necessary to optimize performance.

PMID- 15975390
TI  - Bench repair of donor aortic valve with minimal access orthotopic heart
      transplantation.
AB  - While the number of people waiting heart transplantation increases, the number of
      organ donors decreases. This shrinking donor pool has prompted reassessment of
      donor selection for heart transplantation. Bench repair of a donor aortic valve
      was performed before minimal access orthotopic heart transplantation. Aortic
      insufficiency in the structurally normal tricuspid aortic valve was due to
      annular dilatation and was corrected with subcommissural annular plication. The
      postoperative period was uneventful. Follow-up at 4.5 years showed good results
      and no evidence of aortic regurgitation.

PMID- 15975391
TI  - Reversal of ventricular dilatation in aortic regurgitation after valve
      replacement and cardiac support implant surgery using the CorCap cardiac support
      device.
AB  - The effects of combined aortic valve replacement, coronary bypass surgery, and
      passive containment surgery in a patient with long-standing aortic regurgitation
      and marked ventricular dilatation are described. After surgery there was a rapid
      decrease in left ventricular size and maintained ventricular function.

PMID- 15975392
TI  - Aortic dissection with potential origin from a mechanical bypass anastomosis.
AB  - Ascending aortic dissection is a known complication of cardiac surgery. Off-pump
      coronary artery bypass surgery seems to be associated with a higher risk for this
      event as compared with on-pump bypass surgery. This increased risk may result
      from aortic side-clamping under pulsatile flow as opposed to continuous flow in
      conventional bypass surgery. Mechanical devices allowing performance of proximal
      bypass anastomoses without aortic side-clamping are supposed to reduce the risk
      for aortic dissection. We report a case in which ascending aortic dissection
      occurred 8 days after off-pump bypass surgery, most likely arising from a
      mechanically performed proximal bypass anastomosis.

PMID- 15975393
TI  - Rescue visceral revascularization without direct aortic surgery to treat
      malperfusion complicating type B aortic dissection.
AB  - A 75-year-old woman presented with superior mesenteric artery and celiac artery
      occlusion associated with acute type B dissection. Emergent bypass grafting by
      using the right gastroepiploic artery and the left radial artery for the superior
      mesenteric artery and the celiac artery was performed without bowel resection.

PMID- 15975394
TI  - Successful mitral valve replacement in a patient with Ehlers-Danlos syndrome type
      VI.
AB  - A 40-year-old patient with Ehlers-Danlos syndrome type VI (ocular type) had
      mitral regurgitation due to mitral valve prolapse. Because the patient's tissue
      was fragile, we replaced the mitral valve with a reinforced prosthetic valve to
      prevent paravalvular leakage. The excised mitral leaflet showed significant
      myxomatous change and decrease in collagen fibers. We believe this is the first
      report of cardiac surgery in a patient with Ehlers-Danlos syndrome type VI.

PMID- 15975395
TI  - Tricuspid valve incompetence caused by an intracardiac needle-like foreign body.
AB  - We report a rare case of tricuspid valve incompetence caused by a needle-like
      foreign body with an unknown route of invasion. A 55-year-old woman who had
      suffered from chronic heart failure for more than 25 years was diagnosed as
      having Ebstein's anomaly after a transthoracic echocardiogram with Doppler
      imaging showed severe tricuspid regurgitation and displacement of the septal
      leaflet toward the right ventricle inlet. Surgery revealed a foreign body
      attached to the tricuspid valve, causing regurgitation. Valve replacement was
      performed and the patient's condition improved remarkably thereafter.

PMID- 15975396
TI  - Pulmonary and paradoxical embolism in protein C and S deficient patient.
AB  - We document the case of a 67-year-old woman who presented with a history of right
      upper quadrant anopia, dyspnea, hypoxemia, and a systolic murmur. An intracardiac
      embolus wedged at a patent foramen ovale was successfully removed by resecting
      the atrial septum along with a pulmonary embolectomy on cardiopulmonary bypass.
      We review the literature with specific focus on the pathogenesis and acute
      treatment options of this life-threatening occurrence.

PMID- 15975397
TI  - Cardiac rupture after catheter ablation procedure.
AB  - We describe a patient in whom cardiac tamponade developed owing to left
      ventricular rupture after a catheter ablation procedure. Rapid surgical
      exploration and use of cardiopulmonary bypass facilitated safe repair of the
      injury site and survival of the patient without complications.

PMID- 15975398
TI  - Left ventricular pacing through the anterior interventricular vein in a patient
      with mechanical tricuspid, aortic and mitral valves.
AB  - Transvenous endocardial pacemaker implantation is contraindicated in patients
      after mechanical tricuspid valve replacement. A 76-year-old woman who suffered
      from bradyarrhythmia was implanted with a left ventricular pacing lead through a
      transvenous coronary vein after aortic, mitral, and tricuspid valve replacements.
      There were no complications and the stimulation thresholds were stable. The use
      of coronary vein leads provides a minimally invasive approach, safety, and
      effective stimulation for patients with a mechanical tricuspid valve.

PMID- 15975399
TI  - Ross procedure and ventricular septal defect correction with prolapsed cusp.
AB  - We present the case of an asymptomatic 31-year-old man with perimembranous
      ventricular septal defect and aortic insufficiency due to a prolapsed right cusp.
      The ventricular septal defect was corrected with the rotation of the right cusp,
      and the Ross procedure was performed for the aortic insufficiency. The patient
      had an uneventful postoperative course. At immediate and first year follow-up
      examinations he presented with trivial aortic insufficiency and no residual
      ventricular septal defect. The patient remains asymptomatic with no medication.

PMID- 15975400
TI  - Dor procedure for left ventricular diverticulum with mitral regurgitation in an
      infant.
AB  - Congenital left ventricular diverticulum accompanied by MR is a rare abnormality.
      A 5-month-old female infant with this clinical combination underwent a procedure
      comprising exclusion of a large diverticulum by using an endoventricular circular
      patch (Dor procedure). This technique allowed us to avoid restriction of the left
      ventricular cavity and to improve the orientation of the papillary muscles, thus
      leading to successful mitral valve repair.

PMID- 15975401
TI  - Anomalous left coronary artery, ventricular septal defect, and double aortic
      arch.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery generally
      occurs in isolation. We report an infant diagnosed with double aortic arch and
      ventricular septal defect who was found to have an anomalous origin of the left
      coronary artery from the pulmonary artery at surgery. Successful ventricular
      septal defect repair, division of the arch, and aortic reimplantation of the left
      coronary artery was performed. This article describes a combination of lesions
      previously not described, highlights the altered presentation when multiple
      lesions coexist, discusses the propensity to miss the anomalous coronary, and
      reviews the literature that demonstrates the consequences of overlooking this
      defect.

PMID- 15975402
TI  - Right pulmonary artery-to-left atrium communication: report of 5 cases.
AB  - Five patients of right pulmonary artery-to-left atrium communication presented
      with special emphasis on the clinical presentation, anatomic variations,
      diagnostic considerations, and management options. An individualized management
      algorithm is recommended.

PMID- 15975403
TI  - Nitric oxide in pulmonary arteriovenous malformations and Fontan procedure.
AB  - Pulmonary arteriovenous malformations are a well documented complication of
      superior cavopulmonary (Glenn) connections. We report the successful management
      of a case of severe hypoxemia in the early postoperative period of a patient who
      underwent the Fontan operation. The patient had previously been diagnosed with
      pulmonary arteriovenous malformations; the use of inhaled nitric oxide was
      followed up with reversal of life-threatening hypoxemia. At 6-month postoperative
      follow-up, the patient was asymptomatic with near normal aortic saturation.

PMID- 15975404
TI  - Primary pulmonary collision cancer consisting of large cell carcinoma and
      adenocarcinoma.
AB  - A case of pulmonary collision tumor is herein reported. An abnormal shadow was
      discovered in the right lung of a 53-year-old man. A right upper lobectomy with a
      mediastinal lymph node dissection was performed. Based on the findings of a
      postoperative pathologic examination, this tumor was considered to be a collision
      tumor of large cell carcinoma and adenocarcinoma, as the distribution of each
      tumor was clearly separated. This case is the first report of a primary pulmonary
      collision tumor consisting of large cell carcinoma and adenocarcinoma.

PMID- 15975405
TI  - Lung volume reduction surgery for a professional athlete with Swyer-James
      syndrome.
AB  - Swyer-James syndrome is an uncommon, emphysematous disease characterized by
      roentgenographic hyperlucency of one lung or lobe due to loss of the pulmonary
      vascular structure and to alveolar overdistension. We here describe a 28-year-old
      professional bicycle racer with Swyer-James syndrome who had dyspnea on exertion,
      especially during a bicycle race. Lung volume reduction surgery was performed
      with video-assisted thoracoscopic surgery. This treatment improved his pulmonary
      function, and he is active as a bicycle racer now.

PMID- 15975406
TI  - Clonal light chain restricted primary intrapulmonary nodular amyloidosis.
AB  - Primary intrapulmonary nodular amyloidosis is a rare form of immunoglobulin
      associated amyloidosis, also falling under the alternative appellation of
      amyloidoma. Although amyloidomas in other organ sites may be reflective of a
      localized or more generalized plasma cell dyscrasia, in the context of its
      presentation in the lung the presumptive basis has long been held to be one of
      chronic inflammation. We encountered 2 patients with nodular amyloidosis in whom
      the pathologic examination disclosed the basis to be one of a light chain
      restricted clonal lymphocytic plasma cell infiltrate, although without
      morphologic features of coexisting pulmonary lymphoma. These 2 patients serve to
      underscore the potential categorization of some cases of pulmonary nodular
      amyloidosis as a form of low grade B cell lymphoproliferative disease.

PMID- 15975407
TI  - Destructive sternitis 3 years after blunt chest trauma.

PMID- 15975408
TI  - Delayed esophageal perforation: a complication of anterior cervical spine
      fixation.

PMID- 15975409
TI  - Sequential subxyphoid and thoracotomy incisions with graft pull through for
      targeted redo multivessel surgical revascularization.
AB  - We report on a technique for redo coronary artery bypass using sequential
      subxyphoid and left thoracotomy access and a vascular graft pull through for
      proximal anastomosis to the descending aorta. This technique can be used safely
      on the beating heart when previously implanted grafts to the anterior ventricular
      wall are patent or whenever resternotomy for redo multivessel coronary artery
      bypass is undesirable or contraindicated.

PMID- 15975410
TI  - Hammock-like graft-holding method using a cotton bandage in off-pump coronary
      artery bypass.
AB  - A simple and inexpensive new graft-holding method is described. This method
      requires only a cotton bandage to hold the skeletonized graft in off-pump
      coronary artery bypass. A wet cotton bandage hung between the blades of a
      retractor can hold grafts in an atraumatic fashion at the center of the operating
      field and facilitate anastomosis during off-pump coronary artery bypass.

PMID- 15975411
TI  - Hydrodissection technique of harvesting left internal thoracic artery.
AB  - Use of internal thoracic arteries in coronary artery bypass surgery has become
      universal. Skeletonized internal thoracic artery is useful in coronary artery
      surgery for sequential anastomosis as it also provides a long length of graft.
      Skeletonizing the conduit is technically more difficult than harvesting it as a
      pedicle graft. We describe a technique of harvesting the internal thoracic artery
      in which 10 to 20 mL of normal saline is injected into the fascial plane of the
      left side of chest wall along the course of artery to develop a plane of
      dissection.

PMID- 15975412
TI  - Glutaraldehyde preserved autologous pericardium for patch reconstruction of the
      pulmonary artery and superior vena cava.
AB  - We describe a new employment of glutaraldehyde preserved autologous pericardium
      for patch reconstruction of the pulmonary artery (PA) and superior vena cava
      (SVC). This technique was devised to minimize technical problems related to the
      use of fresh pericardium such as excessive elasticity and tendency to curl. We
      have successfully employed this procedure in three cases of reconstruction of the
      PA and in two cases of reconstruction of the SVC.

PMID- 15975413
TI  - Aspergillus endocarditis after cardiac surgery.
AB  - Aspergillus species infections are an increasingly common occurrence in hospital
      wards. Aspergillus endocarditis constitutes one of the manifestations of the
      disease, which bears a poor prognosis in cardiac surgery patients. A review of
      the literature on fungal and Aspergillus endocarditis was undertaken. Valvular
      risk factors, indwelling intravenous catheters, prolonged antibiotics,
      malignancy, and intravenous drug use increase the risk. Clinical presentation is
      insidious, with embolic complications often representing the first manifestation
      of the disease. Blood cultures are typically negative. The mortality rate is
      almost 100%. Amphotericin B represents the mainstay of medical therapy with
      several possible adjuncts. Surgery is an essential part of therapy in Aspergillus
      endocarditis after cardiac surgery and should be undertaken as soon as the
      diagnosis is made. Aspergillus endocarditis is an ominous complication after
      cardiac surgery. A high suspicion index, early administration of appropriate
      antibiotics, and prompt surgical intervention should improve the prognosis, which
      remains dismal.

PMID- 15975414
TI  - Right pulmonary artery to left atrium communication.
AB  - This is a collective review of 59 published cases of right pulmonary artery to
      left atrium communication in the English-language literature. In this article, we
      review the literature on the clinical presentation, anatomic variations,
      diagnostic features, and management considerations of previously reported cases.
      Two-dimensional echocardiography and cardiac catheterization including selective
      angiography provided the necessary diagnostic information and defined the anatomy
      before surgery in all patients. Various management options including medical,
      surgical, and transcatheter closure have been reported. The lesions have been
      classified into four types (I, II, III, and IV) that have a bearing on the
      appropriate surgical approach and techniques of repair that are discussed in the
      text. Use of extracorporeal circulation may be considered in selected instances.
      The operative mortality rate during the earlier era (1950 to 1979) was high, at
      22%. More recently, the mortality rate has approached zero. An individualized
      surgical approach depending on the type of surgical connections is recommended.

PMID- 15975416
TI  - Practical reasons to review cases for plaintiffs.

PMID- 15975418
TI  - A recent graduate's perspective on residency training.

PMID- 15975420
TI  - Apolipoprotein E polymorphism and the risk of acute nephropathy after cardiac
      surgery.

PMID- 15975422
TI  - Weight as a risk factor of mediastinitis after cardiac surgery in context of
      insufficient dosage of prophylactic antibiotic.

PMID- 15975423
TI  - Acute type A dissection and advanced age.

PMID- 15975426
TI  - End-to-end anastomosis for ascending aortic aneurysm.

PMID- 15975428
TI  - Intercostal muscle flaps.

PMID- 15975430
TI  - RNA transcript profiling during zygotic gene activation in the preimplantation
      mouse embryo.
AB  - Zygotic gene activation is essential for development beyond the 2-cell stage in
      the preimplantation mouse embryo. Based on alpha-amanitin-sensitive BrUTP
      incorporation, transcription initiates in the 1-cell embryo and a major
      reprogramming of gene expression driven by newly expressed genes is prominently
      observed during the 2-cell stage. Superimposed on genome activation is the
      development of a transcriptionally repressive state that is mediated at the level
      of chromatin structure. The identity of the genes that are expressed during the 1
      and 2-cell stages, however, is poorly described, as are those genes involved in
      mediating the transcriptionally repressive state. Using the Affymetrix MOE430
      mouse GeneChip set, we characterized the set of alpha-amanitin-sensitive genes
      expressed during the 1- and 2-cell stages, and we used Expression Analysis
      Systematic Explorer (EASE) and Ingenuity Pathway Analysis (IPA) to identify
      biological and molecular processes represented by these genes, as well as
      interactions among them. We find that although the 1-cell embryo is
      transcriptionally active, we did not detect any transcripts present on the MOE430
      GeneChip set to be alpha-amanitin-sensitive. Thus, what the BrUTP incorporation
      represents remains elusive. About 17% of genes expressed in the 2-cell embryo are
      alpha-amanitin-sensitive. EASE analysis reveals that genes involved in ribosome
      biogenesis and assembly, protein synthesis, RNA metabolism and transcription are
      over-represented, suggesting that genome activation during 2-cell stage may not
      be as global and promiscuous as previously proposed. IPA implicated Myc and Hdac1
      as candidate genes involved in genome activation and the development of the
      transcriptionally repressive state, respectively.

PMID- 15975429
TI  - xBtg-x regulates Wnt/beta-Catenin signaling during early Xenopus development.
AB  - In Xenopus, two signaling systems, maternal beta-Catenin and Nodal-related, are
      required for induction of the Spemann organizer and establishment of the body
      plan. By screening cDNA macroarrays for genes activated by these two signaling
      pathways, we identified Xenopus xBtg-x, a novel member of the Btg/Tob gene family
      of antiproliferative proteins. We show that xBtg-x is expressed in the dorsal
      mesendoderm (Spemann organizer tissue) of gastrula stage embryos and that its
      expression is regulated by both beta-Catenin and Nodal-related signals.
      Microinjection of synthetic xBtg-x mRNA into Xenopus embryos induced axis
      duplication and completely rescued the ventralizing effects of UV irradiation
      through the activation of the canonical Wnt/beta-Catenin signaling pathway.
      Interestingly, xBtg-x stimulated beta-Catenin-dependent transcription without
      affecting the stability of beta-Catenin protein. These data suggest that xBtg-x
      is a novel component of the Wnt/beta-Catenin signaling pathway regulating early
      embryonic patterning.

PMID- 15975431
TI  - Proteolytic processing of myostatin is auto-regulated during myogenesis.
AB  - Myostatin, a potent negative regulator of myogenesis, is proteolytically
      processed by furin proteases into active mature myostatin before secretion from
      myoblasts. Here, we show that mature myostatin auto-regulates its processing
      during myogenesis. In a cell culture model of myogenesis, Northern blot analysis
      revealed no appreciable change in myostatin mRNA levels between proliferating
      myoblasts and differentiated myotubes. However, Western blot analysis confirmed a
      relative reduction in myostatin processing and secretion by differentiated
      myotubes as compared to proliferating myoblasts. Furthermore, in vivo results
      demonstrate a lower level of myostatin processing during fetal muscle development
      when compared to postnatal adult muscle. Consequently, high levels of circulatory
      mature myostatin were detected in postnatal serum, while fetal circulatory
      myostatin levels were undetectable. Since Furin proteases are important for
      proteolytically processing members of the TGF-beta superfamily, we therefore
      investigated the ability of myostatin to control the transcription of furin and
      auto-regulate the extent of its processing. Transfection experiments indicate
      that mature myostatin indeed regulates furin protease promoter activity. Based on
      these results, we propose a mechanism whereby myostatin negatively regulates its
      proteolytic processing during fetal development, ultimately facilitating the
      differentiation of myoblasts by controlling both furin protease gene expression
      and subsequent active concentrations of mature myostatin peptide.

PMID- 15975432
TI  - Manifestations of multicellularity: Dictyostelium reports in.
AB  - The recent release of the Dictyostelium genome sequence is important because
      Dictyostelium has become a much-favoured model system for cell and developmental
      biologists. The sequence has revealed a remarkably high total number of
      approximately 12 500 genes, only a thousand fewer than are encoded by Drosophila.
      Previous protein-sequence comparisons suggested that Dictyostelium is
      evolutionarily closer to animals and fungi than to plants, and the global protein
      sequence comparison, now made possible by the genome sequence, confirms this.
      This review focuses on several classes of proteins that are shared by
      Dictyostelium and animals: a highly sophisticated array of microfilament
      components, a large family of G-protein-coupled receptors and a diverse set of
      SH2 domain-containing proteins. The presence of these proteins strengthens the
      case for a relatively close relationship with animals and extends the range of
      problems that can be addressed using Dictyostelium as a model organism.

PMID- 15975433
TI  - Refractive lens exchange: ethical considerations in the informed consent process.

PMID- 15975434
TI  - Persistent diplopia after retrobulbar anesthesia.

PMID- 15975436
TI  - Proper statistical methods required to compare clinical measurements.

PMID- 15975439
TI  - High-order aberrations in pseudophakia with different IOLs.

PMID- 15975440
TI  - Aggravation of proliferative diabetic retinopathy after laser in situ
      keratomileusis.

PMID- 15975441
TI  - Long-term results of deep sclerectomy with collagen implant.

PMID- 15975442
TI  - Consultation section: refractive surgical problem.

PMID- 15975450
TI  - Intraocular contact lens tamponade to facilitate penetrating keratoplasty in
      perforated corneas.
AB  - Penetrating keratoplasty in the presence of a perforated cornea is a relatively
      common and difficult surgical problem. In the worst scenario, there may be
      extrusion of ocular contents during trephination. Two cases of perforated corneas
      are presented in which a new technique was used to close the perforation and
      normalize intraocular pressure. This involves inserting a soft contact lens
      through a paracentesis into the anterior chamber. An ophthalmic viscosurgical
      device is then injected behind the contact lens, opening it, and allowing it to
      tamponade the perforation. This stabilizes the anterior chamber and allows a
      stable operating environment. This has not been described previously.

PMID- 15975451
TI  - Epi-LASIK: preliminary clinical results of an alternative surface ablation
      procedure.
AB  - PURPOSE: To evaluate the clinical results of epi-LASIK, a new surface ablation
      surgical technique for the treatment of low myopia. SETTING: Vardinoyannion Eye
      Institute of Crete, University of Crete, Greece. METHODS: Forty-four eyes of 31
      patients had epi-LASIK for the correction of low myopia. Mean preoperative
      spherical equivalent was 3.71 diopters (D) +/- 1.2 (SD) (range -1.75 to -7.00 D)
      and the mean baseline logMAR best spectacle-corrected visual acuity was -0.01 +/-
      0.06 (range 0.10 to -0.10). All the epithelial separations were performed with
      the Centurion epikeratome (CIBA Surgical). The enrolled patients were followed
      daily until the epithelial healing was complete as well as at 1- and 3-month
      intervals. On the operative day, patients filled out a questionnaire grading
      visual performance and pain score of treated eyes every 2 hours for a total of 5
      records. RESULTS: The mean epithelial healing time was 4.86 +/- 0.56 days (range
      3 to 5 days). The mean logMAR uncorrected visual acuity on the day of
      reepithelization was 0.19 +/- 0.09 (range 0.40 to 0.10). At 1 month, the mean was
      spherical equivalent of the treated eyes (N=44), -0.3 +/- 0.6 D (range -1.0 to
      0.87 D), and at 3 months it was (N=37), -0.10 +/- 0.4 D (range -0.75 to 0.75 D);
      97% of eyes had clear corneas or trace haze 3 months after treatment.
      CONCLUSIONS: Preliminary clinical results suggest that epi-LASIK is a safe and
      efficient method for the correction of low myopia. Further studies will establish
      this method as an alternative surface ablation procedure.

PMID- 15975452
TI  - Posterior vertical capsulotomy with optic entrapment of the intraocular lens in
      congenital cataracts--prevention of capsule opacification.
AB  - PURPOSE: To present a modified surgical technique for preventing posterior
      capsule opacification (PCO) in children with congenital cataracts and to evaluate
      its long-term efficacy. SETTING: Department of Ophthalmology, Medical University
      of Southern Africa, Medunsa, South Africa. METHODS: Anterior and posterior
      vertical capsulotomy, with optic entrapment of the intraocular lens (IOL) by
      maintaining the anterior hyaloid, was performed in 68 cataractous eyes of
      children aged 2 months to 8 years (mean 3 years, 1 month). The posterior capsule
      was evaluated for at least 5 years for secondary opacification, IOL position,
      pigmentary deposits on the IOL optic, and the presence of synechias. RESULTS:
      Sixty-eight eyes maintained a clear visual axis for 5 to 12 years (mean 9 years,
      1 month) postoperatively. No secondary procedure was necessary. In all eyes, the
      IOL remained well centered and entrapped. CONCLUSIONS: Posterior capsulotomy with
      optic entrapment of the IOL proved to be a safe and efficient surgical procedure
      for preventing PCO in children with congenital cataracts. Uniting the anterior
      and posterior capsule in front of the IOL limits the proliferation and migration
      of Elschnig pearls. An intact anterior hyaloid does not induce capsule
      opacification in association with optic entrapment; therefore, a vitrectomy is
      not indicated even in infants under age 5 years. Clear visual axis, centered IOL,
      and intact vitreous were achieved in this series; this enables a promising long
      term prognosis for binocular visual development, especially because surgery was
      performed early.

PMID- 15975453
TI  - Early visual results with the 1CU accommodating intraocular lens.
AB  - PURPOSE: To prospectively assess the clinical outcome after implantation of the
      1CU accommodating intraocular lens (IOL) and a foldable acrylic IOL (AcrySof,
      Alcon). SETTING: Department of Ophthalmology, Tokyo Dental College, Ichikawa
      Hospital, Ichikawa, and Minami Aoyama Eye Clinics, Tokyo, Yokohama, Japan.
      METHODS: Twenty-two eyes of 16 patients with cataract had phacoemulsification
      implantation of 1CU accommodating IOL. Twenty eyes of 10 age-matched and sex
      matched patients with cataract had the same surgery but with a foldable acrylic
      IOL. All patients had assessments of the amplitude of accommodation, refraction,
      uncorrected and best corrected distance and near visual acuity, and distance
      corrected near visual acuity before surgery up to 12 months after surgery.
      Contrast visual acuities were measured 1 year after surgery. Anterior segment
      photography, intraocular pressure measurements, specular microscopy, and
      computerized topography were also performed. RESULTS: The final best corrected
      distance visual acuity was above 20/25 in all eyes with the 1CU and the AcrySof
      IOLs. The mean distance corrected near visual acuity was significantly higher in
      the 1CU IOL group than in the acrylic IOL group after 3 months. None of the eyes
      with the AcrySof IOL implants displayed an accommodative response at any
      examination. The peak mean amplitude of accommodation with the 1CU IOLs was
      observed at 3 months and was 0.5 diopters +/- 0.44 (SD). Accommodation amplitude
      declined after 6 months. CONCLUSION: The 1CU IOL provided additional near acuity
      postoperatively, but the benefit disappeared at 12 months with a concomitant
      decrease in accommodation amplitude owing to an increase in anterior and
      posterior capsular opacities.

PMID- 15975454
TI  - Anterior chamber and sutured posterior chamber intraocular lenses in eyes with
      poor capsular support.
AB  - PURPOSE: To compare the clinical outcomes and complications of patients who had
      surgical placement of anterior chamber (AC IOLs) and sutured posterior chamber
      intraocular lenses (PC IOLs) after cataract surgery resulting in poor capsular
      support. SETTING: Department of Ophthalmology, Bascom Palmer Eye Institute,
      Miami, Florida. METHODS: A retrospective interventional comparative case series
      of 181 eyes of 181 patients that had implantation of an intraocular lens with
      inadequate capsular support was conducted. A chart review of all patients that
      had implantation of AC IOLs or sutured PC IOLs at a tertiary care eye hospital
      between 1995 and 2001 was conducted. RESULTS: Outcome measures included final
      best-corrected visual acuity, spherical equivalent, and postoperative
      complications (pseudophakic bullous keratopathy, elevated intraocular pressure
      [IOP] inflammation, retinal detachment, suture erosion, cystoid macular edema).
      Of 702 charts reviewed, 181 were found to fit inclusion and exclusion criteria.
      The postoperative complication risk ratio was 0.80 (95% confidence interval [CI]:
      0.52-1.23) for AC IOLs compared with PC IOLs. The most common complication
      experienced by patients having implantation of either lens type was elevated IOP
      (AC IOL: 38%; PC IOL: 42%). The incidence of other complications was similar
      between the groups. Best-corrected visual acuity was similar; however, final
      spherical equivalent trended toward more myopic values in the PC IOL group (-0.82
      +/- 1.67 for AC IOL versus -1.32 +/- 2.12 for PC IOL). CONCLUSIONS: The findings
      suggest that no significant differences in outcome exist when comparing AC IOLs
      to sutured PC IOLs in complicated cataract extraction with poor capsular support.
      Recent advances in AC IOL design have yielded lenses that provide a safe,
      effective alternative to sutured PC IOLs.

PMID- 15975455
TI  - Experience with the Artisan phakic intraocular lens in Asian eyes.
AB  - PURPOSE: To investigate the efficacy and safety of implantation of an iris-claw
      phakic intraocular lens (PIOL), Artisan Myopia, in Asian eyes. SETTING:
      Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: Forty-four eyes of 32 Japanese
      patients and 1 Korean patient with high myopia had Artisan Myopia lens
      implantation to correct their refractive errors. Lens models, 5/8.5 or 6/8.5
      (optic diameter/overall diameter), were chosen as standard lens model. A smaller
      lens model (5/7.5-Artisan Myopia Small) was implanted in eyes with corneal
      diameter less than 11.0 mm. Postoperative examinations were performed on 1 day, 1
      week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. Uncorrected
      visual acuity (UCVA), best corrected visual acuity (BCVA), manifest refraction,
      corneal endothelial cell counts, intraocular pressure, and complications were
      evaluated. RESULTS: Artisan Myopia Small lenses were implanted in 4 eyes (9.1%)
      and 8.5 mm diameter lenses were implanted in 40 eyes. Preoperative UCVA (logMAR)
      improved from 1.57 to 0.09 at 1 month after surgery and no regression was
      observed thereafter. Postoperative manifest refraction was -1.02 +/- 0.87 D (
      3.25 to -0.00 D), and within 1.0 D in 20 eyes (55.6%), within 2.0 D in 32 eyes
      (88.9%) at 1 month after surgery, and stable during the follow-up period. The
      final BCVA decreased 2 lines in 2 eyes (4.5%) due to progression of age-related
      cataract. No serious complications such as angle closure or progressive
      endothelial cell loss were observed. CONCLUSION: Implantation of an Artisan iris
      claw PIOL implantation may be a safe and effective procedure for Asian eyes.

PMID- 15975456
TI  - Flap suturing with proparacaine for recurrent epithelial ingrowth following laser
      in situ keratomileusis surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of flap suturing with proparacaine
      application for the management of recurrent epithelial ingrowth following laser
      in situ keratomileusis (LASIK). SETTING: Private consultation practice and
      Department of Ophthalmology, Rush University, Chicago, Illinois, USA. METHODS:
      Six eyes of 5 patients with recurrent epithelial ingrowth had flap lifting
      followed by debridement of interface epithelial cells, interface application of
      proparacaine, and the placement of interrupted 10-0 nylon sutures. RESULTS: Four
      eyes achieved a best corrected visual acuity (BCVA) of 20/40 or better. Two eyes
      required repeat debridement with suturing and were stable with at least a 1-year
      follow-up. No eye lost more than 1 line of BCVA. Three eyes regained excellent
      uncorrected visual acuity due to a reduction in induced astigmatism. CONCLUSIONS:
      Recurrent epithelial ingrowth following LASIK surgery can be a visually
      debilitating condition. Flap suturing with interface proparacaine application may
      be effective in preventing further recurrences of epithelial ingrowth after
      initial debridement.

PMID- 15975457
TI  - Noninflammatory flap edema after laser in situ keratomileusis associated with
      asymmetrical preoperative corneal pachymetry.
AB  - PURPOSE: To report persistent unilateral flap edema following laser in situ
      keratomileusis (LASIK) in patients with asymmetrical central corneal thickness.
      SETTING: Minnesota Eye Consultants, Minneapolis, Minnesota. METHODS:
      Retrospective, noncomparative interventional case series. RESULTS: We examined 6
      eyes of 3 patients with asymmetrical preoperative pachymetry who developed
      persistent unilateral flap edema after uneventful myopic LASIK in the eye with
      thicker preoperative pachymetry. All cases had asymmetrical preoperative
      pachymetry with flap edema developing in the eye with higher preoperative mean
      central corneal thickness (CCT) values, preoperative mean CCT subject eye 622
      microm (range 556-664 microm) versus fellow eye 583 microm (range 510-621
      microm). There was no associated ocular inflammation or rise in intraocular
      pressure. Significant flap edema resolved on a combination treatment of topical
      steroid and hypertonic saline. CONCLUSIONS: Laser in situ keratomileusis can
      cause temporary endothelial cell dysfunction or stress, which manifests as
      temporary flap edema and subclinical corneal thickening. The edema appears to be
      limited to the actual flap and there was no loss of epithelial integrity in these
      eyes and no clinically noticeable interface fluid. This new clinical entity
      appears to occur in patients with asymmetrical preoperative corneal pachymetry
      and is associated with postoperative specular microscopy abnormalities. In cases
      with unexplained asymmetrical corneal thickness, preoperative evaluation should
      include specular microscopy to evaluate for risk features that may increase the
      chances of a slower postoperative recovery.

PMID- 15975458
TI  - Corneal epithelial healing after photorefractive keratectomy: analytical study.
AB  - PURPOSE: To characterize the velocity of epithelial migration after
      photorefractive keratectomy (PRK) with 3 different corneal ablation patterns.
      SETTING: Department of Ophthalmology, Catholic University of Rome, Rome, Italy.
      METHODS: Fifteen patients (30 eyes) with mild to moderate myopia and with simple
      to compound myopic astigmatism were enrolled for this study. The surgical
      procedure consisted of standardized PRK with final smoothing performed using the
      Technolas Keracor 217C excimer laser. The reepithelialization process was
      evaluated at 0 hours, 20 hours, 40 hours, and 60 hours after surgery using a
      digital photo camera and custom software for measurement. Digital analysis of the
      images was performed. Corneal topographies were taken at 1 month, 3 months, 6
      months, and 12 months after PRK. RESULTS: The mean speed of radial migration in
      the 10 eyes (33%) in the low spherical ablation group was 0.087 mm/h +/- 0.008
      (SD). This was significantly higher than that found in the 10 eyes (33%) in the
      high spherical ablation group (mean speed 0.078 +/- 0.007 mm/h; P<.001) and in
      the 10 eyes (33%) in the cross-cylinder ablation group (mean speed 0.055 +/-
      0.014 mm/h; P<.001). CONCLUSION: Analysis of the data shows that epithelial
      migration along the photoablated corneal surface depends on the ablation pattern.
      The epithelial sliding is highly influenced by local variations in the curvature
      of the stromal surface. The data demonstrate that faster epithelial wound healing
      after PRK is predictive of optimal visual performance.

PMID- 15975459
TI  - Safety of trypan blue 1% and indocyanine green 0.5% in assisting visualization of
      anterior capsule during phacoemulsification in mature cataract.
AB  - PURPOSE: To evaluate the safety of trypan blue 1% and indocyanine green (ICG)
      0.5% in assisting visualization of anterior capsule during phacoemulsification in
      mature cataract. SETTING: Department of Ophthalmology, United Christian Hospital,
      Hong Kong, China. METHODS: This prospective randomized clinical trial comprised
      46 eyes with mature cataract receiving phacoemulsification and posterior chamber
      intraocular lens implantation. They were randomized into 3 groups (trypan blue,
      ICG, and control without stain). Visual acuity, endothelial cell count, corneal
      clarity, anterior chamber reaction, and intraocular pressure (IOP) were
      documented before surgery and 1 week, 1 month, and 3 months postoperatively. The
      absolute phaco time was also recorded. RESULTS: There was no significant
      difference in absolute phaco time (P=.17), mean endothelial cell loss (P=.72 at 1
      week, P=.43 at 1 month, and P=.60 at 3 months) and no significant correlation
      between the absolute phaco time and the change in endothelial cell count (P=.50
      at 1 week, P=.10 at 1 month, and P=.60 at 3 months) in the 3 groups. None of the
      patients had postoperative IOP greater than 21 mm Hg. All eyes had clear corneas
      and a quiet anterior chamber 3 months after surgery. CONCLUSION: Both trypan blue
      1% and ICG 0.5% are safe for assisting visualization of the anterior capsule
      during phacoemulsification of mature cataract.

PMID- 15975460
TI  - One or 2 Intacs segments for the correction of keratoconus.
AB  - PURPOSE: To evaluate the effect of implanting 1 or 2 intracorneal rings (Intacs,
      KeraVision) as a device to correct, stabilize, and/or improve the best corrected
      visual acuity in patients with clear cornea keratoconus oriented by the
      preoperative corneal topography pattern. SETTING: Vissum/Instituto Oftalmologico
      de Alicante, Miguel Hernandez University, Alicante, Spain. METHODS: In this
      prospective comparative consecutive study, Intacs segments were implanted in 26
      keratoconic eyes with clear central corneas of 19 consecutive patients (9 women
      and 10 men). Corneas were divided into 2 groups according to the topographic
      pattern of the cone. Group I included keratoconus not crossing the 180 degrees
      meridian and Group II included keratoconus crossing the 180 degrees meridian. The
      Intacs were horizontally placed through a lateral clear corneal incision.
      According to the corneal topography 1 segment was implanted 0.45 mm inferior in
      Group I, and 2 segments were implanted, 1 0.25 mm superior and the other 0.45 mm
      inferior, in Group II. All cases completed a minimum follow-up of 1 year.
      Differences between preoperative and postoperative uncorrected visual acuity
      (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, and
      keratometry were clinically and statistically evaluated. RESULTS: Spherical
      equivalent error and refractive astigmatism were significantly reduced. The mean
      keratometric values were reduced following Intacs insertion in both groups. At
      the end of the first year of the postoperative follow-up, Group I (1 segment) had
      an improvement in mean UCVA to 20/50 (0.4 +/- 0.22 decimal value), which was
      statistically significant when compared to the preoperative UCVA of 20/100 (0.2
      +/- 0.13 decimal value) (P=.011). Mean BSCVA was 20/32 (0.62 +/- 0.24 decimal
      value), which was also statistically significant when compared to the
      preoperative BSCVA, which was 20/50 (0.4 +/- 0.21 decimal value) (P=.002). In
      Group II (2 segments), UCVA after 1 year was 20/63 (0.34 +/- 0.17 decimal value),
      which was statistically significant when compared to the preoperative UCVA of
      20/400 (0.06 +/- 0.02 decimal value) (P=.001). Mean BSCVA was 20/32 (0.62 +/-
      0.27 decimal value), which was significantly better than the preoperative UCVA of
      20/50 (0.38 +/- 0.22 decimal value) (P=.001). In 4 eyes, the inferior segment was
      removed because of partial extrusion during the postoperative follow-up.
      CONCLUSIONS: Treatment of keratoconus with 1 or 2 Intacs segments oriented by the
      preoperative corneal topography used in this study proved to be effective in
      decreasing the corneal steepening and astigmatism and improving BSCVA. Further
      follow-up is needed to determine the final effect of Intacs on the progression of
      the corneal disease.

PMID- 15975461
TI  - Long-term effect of optic edge design in an acrylic intraocular lens on posterior
      capsule opacification.
AB  - PURPOSE: To compare the posterior capsule opacification (PCO) inhibiting effect
      of the sharp posterior optic edge design of the Sensar OptiEdge AR40e intraocular
      lens (IOL) with that of the double-round edge design of the Sensar AR40 IOL over
      a period of 3 years. SETTING: Department of Ophthalmology, Medical University of
      Vienna, Vienna, Austria. METHODS: Fifty-three patients with bilateral age-related
      cataract (106 eyes) were included in this randomized prospective bilateral
      patient- and examiner-masked clinical trial with intraindividual comparison. Each
      study patient had cataract surgery in both eyes and received a Sensar AR40 IOL
      (anterior and posterior round optic edges) in 1 eye and a Sensar OptiEdge AR40e
      IOL (round anterior and sharp posterior optic edge) in the other eye. Follow-up
      examinations were at 1 week, 1 and 6 months, and 1, 2, and 3 years. Digital
      retroillumination images were taken of each eye. The amount of PCO was assessed
      subjectively at the slitlamp and objectively using automated image-analysis
      software (AQUA) 1, 2, and 3 years after surgery. RESULTS: The sharp-edged AR40e
      lens showed significantly less regeneratory and fibrotic PCO 1, 2, and 3 years
      after surgery. The mean AQUA PCO score was 2.18 for the AR40 and 1.00 for the
      AR40e lens after 1 year; 2.94 and 1.56 after 2 years, and estimated at 3.13 and
      1.77, respectively, after 3 years (scale 0 to 10; P<.001). The neodymium:YAG
      laser capsulotomy rate was significantly higher in the AR40 group. The AR40e lens
      also led to less peripheral fibrotic PCO. There was no significant difference in
      complaints concerning edge glare between the groups. CONCLUSION: Compared with
      the AR40 IOL, the sharp posterior optic edge design of the Sensar OptiEdge AR40e
      IOL led to significantly less PCO 1, 2, and 3 years postoperatively. In contrast
      with most past studies on PCO-preventative factors, this study varied only 1
      parameter, namely the optic edge design, and the main outcome measure (PCO) was
      assessed with an objective image-analysis system.

PMID- 15975462
TI  - Short-term changes in the morphology of posterior capsule opacification.
AB  - PURPOSE: To observe and document posterior capsule opacification (PCO) growth in
      vivo over a short period of time (4 weeks). SETTING: Department of Ophthalmology,
      Medical University of Vienna, Vienna, Austria. METHODS: Fifteen eyes of
      pseudophakic patients with PCO of varying degrees were included in this
      prospective study. Digital retroillumination images were taken in a standardized
      fashion at 3 time points: 1 baseline image, a second image after 2 weeks, and a
      third image after 4 weeks. Thus, a 3-image series could be created for each eye.
      Additionally, sections of the posterior capsule with interesting structures were
      photographed with higher magnification and compared in supplementary image
      series. Morphologic changes in the PCO structure (eg, number and size of Elschnig
      pearls, total PCO area) were analyzed in the image series. RESULTS: In all cases,
      significant changes could be observed between the 3 time points. In 71% of cases,
      some Elschnig pearls increased in size during the first 2 weeks and during weeks
      3 and 4. In 73% of cases, however, there was a reduction a pearl size or even
      disappearance of some Elschnig pearls. The total PCO area did not change
      significantly during the 4-week period. CONCLUSIONS: Development of
      (regeneratory) PCO is a very dynamic process that includes not only growth of
      preexisting structures and occurrence of new Elschnig pearls, but also
      reorganization and even disappearance of pearls within a short time period (2-4
      weeks). The latter in particular is not well known but could be observed in the
      majority of cases in this study.

PMID- 15975463
TI  - Influence of intraocular lens optical design on high-order aberrations.
AB  - PURPOSE: To compare differences in high-order aberrations (HOAs) between 2
      intraocular lens (IOL) optical designs. SETTING: Department of Ophthalmology,
      Nara Medical University, Nara, Japan. METHOD: Sixty eyes that had uncomplicated
      phacoemulsification and IOL implantation were assigned to 1 of 2 groups based on
      the type of IOL optical design: more posteriorly curved biconvex shape (AcrySof
      MA30BA, Alcon) (n=30 eyes) or more anteriorly curved biconvex shape (AcrySof
      MA30AC) (n=30 eyes). All patients had best corrected visual acuity better than
      20/25. High-order aberrations were measured using a Hartmann-Shack aberrometer at
      4.0 mm and 6.0 mm wavefront aperture diameters. RESULTS: At 4.0 mm aperture
      diameters, there were no differences between the 2 groups in HOAs (P>.05, Mann
      Whitney U test) in the cornea and the whole eye. At 6.0 mm aperture diameters,
      MA30AC eyes had a smaller amount of spherical-like aberrations (P=.043) than
      MA30BA eyes; however, there were no significant differences between the 2 groups
      in coma-like aberrations and total aberrations in the whole eye (P>.05). At 6.0
      mm aperture diameters, there were no differences between the 2 groups HOAs in the
      cornea. (P>.05). CONCLUSION: The optical design of the spherical IOL influenced
      the spherical-like aberrations in the whole eye. This may reduce retinal image
      quality.

PMID- 15975464
TI  - Spontaneous alterations of the corneal topographic pattern.
AB  - PURPOSE: To assess whether the type of corneal topographic pattern is stable
      during a 1-minute pause in blinking in healthy subjects. SETTING: First
      Department of Ophthalmology, Semmelweis University, Budapest, Hungary. METHODS:
      Corneal topographic images were recorded 5, 15, 30, and 60 seconds after a
      complete blink in the right eyes of 36 healthy subjects using the TMS-1
      instrument in a prospective observational study. The topographic pattern of each
      image was assessed from the color-coded topographic map and classified into 5
      groups (in order of decreasing regularity: round, oval, symmetric bow-tie,
      asymmetric bow-tie, and irregular). RESULTS: During the 60-second period, a
      change in the type of topographic pattern was found in 19 subjects (53%), whereas
      in 17 subjects (47%) the pattern was stable. The alteration of the topographic
      pattern was statistically significant (P<.001). CONCLUSIONS: Immediately after
      blinking, the ocular surface regularity improves, possibly due to the building up
      of the tear film. This is followed later by the distortion of the ocular surface,
      which is the precursor of the tear-film break up phenomenon. Because of these
      changes, even in healthy eyes, the optimization and standardization of the
      postblink time of topographic image capture are very important, especially for
      planning refractive surgery.

PMID- 15975465
TI  - Laser in situ keratomileusis for refractive error after cataract surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of laser in situ keratomileusis
      (LASIK) to correct refractive error following cataract surgery. SETTING: The Eye
      Institute, Sydney, Australia. METHODS: This retrospective study reviewed 23 eyes
      (19 patients; 10 female, 9 male) treated with LASIK for refractive error
      following cataract surgery. The Summit Apex Plus and Ladarvision excimer laser
      and the SKBM microkeratome were used. The mean age was 63.5 years (range 50 to 88
      years). The mean length of follow-up was 8.4 months (range 1 to 12 months) and
      mean interval between cataract surgery and LASIK was 12 months (range 2.5 to 46
      months). RESULTS: The mean preoperative spherical equivalent refraction (SEQ) for
      myopic eyes was -3.08 +/- 0.84 diopters (D) (range -4.75 to -2.00 D) and for
      hyperopic eyes was +1.82 +/- 1.03 D (range +0.75 to +3.00 D). The mean
      improvement following LASIK surgery was greater for myopic than hyperopic eyes
      (myopic, 2.54 +/- 1.03 D versus hyperopic, 1.73 +/- 0.62 D; P=.033). The
      percentage of patients within +/-0.5 D of intended refraction post-LASIK surgery
      was 83.3% for myopic eyes and 90.9% for hyperopic eyes and all eyes were within
      +/-1.0 D of intended (P<.001). The percentage of eyes with uncorrected visual
      acuity of 20/40 or better in the myopic group improved from none preoperatively
      to 91.7% postoperatively (P<.001) and in the hyperopic group improved from 27.3%
      preoperatively to 90.9% postoperatively (P=.008). No eyes lost 2 or more lines of
      best corrected visual acuity. CONCLUSION: Laser in situ keratomileusis appears to
      be effective in correcting refractive error following cataract surgery. Longer
      term studies are required to determine refractive stability.

PMID- 15975466
TI  - Six-month variability of the dark-adapted pupil diameter.
AB  - PURPOSE: To determine the individual variability of the dark-adapted pupil
      diameter over 6 months using a standardized dark-adaptation protocol. SETTING:
      Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: This
      prospective observational cohort study comprised volunteers with no history of
      ocular disease, surgery, or injury other than requirement for refractive
      correction. The right eye was tested. A standardized dark-adaptation protocol was
      used that controlled for accommodation and patient alertness. Infrared, still
      digital photographs were taken after 10 minutes of dark adaptation at 1 lux and
      were analyzed using digital image software. Testing was performed at baseline in
      the afternoon, at 3 months in the afternoon, and at 6 months in the morning.
      Lifestyle factors such as diet and exercise were not controlled. RESULTS: Mean
      intersession differences were 0.04 mm (95% confidence interval [CI]: -0.68
      0.146), 0.15 mm (95% CI: -0.001-0.297), and 0.09 mm (95% CI: -0.048-0.236) for
      baseline-3 month, baseline-6 month, and 3 month-6 month comparisons,
      respectively. None of these differences was significantly different from zero
      (P>.05, 2-tailed Student t tests). The likelihood that the mean intersession
      difference was >.25 mm was negligible for all comparisons (P=.9996, .9099, and
      .9829 respectively, 1-tailed Student t tests). CONCLUSION: When a consistent dark
      adaptation protocol that controls for alertness and accommodation is used, normal
      young individuals showed no significant variation in the dark-adapted pupil
      diameter over a 6-month period.

PMID- 15975467
TI  - Perioperative use of warfarin and aspirin in cataract surgery by Canadian Society
      of Cataract and Refractive Surgery members: survey.
AB  - PURPOSE: To survey the members of the Canadian Society of Cataract and Refractive
      Surgery (CSCRS) and identify their practices regarding the perioperative use of
      warfarin and acetylsalicylic acid (aspirin) in cataract surgery. SETTING: Private
      practice, Regina, Saskatchewan, Canada. METHODS: Members of the CSCRS were faxed
      a questionnaire that examined their perioperative management of patients being
      treated with warfarin and aspirin. RESULTS: Of the 110 eligible participants, 82
      returned a completed questionnaire, representing a response rate of 74.5%.
      Warfarin or aspirin was routinely stopped prior to cataract surgery by 25.6% of
      the respondents. The majority of surgeons who discontinued these medications
      reported doing so 3 to 7 days prior to surgery and resumed their use 1 to 2 days
      postoperatively. Topical anesthesia and clear corneal incisions were preferred by
      the higher volume surgeons. These surgeons were also less likely to discontinue
      either warfarin or aspirin preoperatively. CONCLUSIONS: The majority of the
      Canadian Society of Cataract and Refractive Surgery members do not stop either
      warfarin or aspirin for cataract surgery during the perioperative period.

PMID- 15975468
TI  - Outcomes of phacoemulsification and in-the-bag intraocular lens implantation in
      Fuchs' heterochromic iridocyclitis.
AB  - PURPOSE: To evaluate the visual outcomes and complications of phacoemulsification
      (PE) and posterior chamber intraocular lens implantation, (PC IOL) in patients
      with Fuchs heterochromic iridocyclitis (FHIC). SETTING: Private clinic and an
      academic hospital. METHODS: In this noncomparative interventional case series,
      existing data for 41 eyes of 40 consecutive patients clinically diagnosed with
      FHIC and cataract were studied retrospectively. Scleral tunnel PE and in-the-bag
      IOL implantation were performed in all cases. Preoperative and postoperative
      visual acuities and intraoperative and postoperative complications were
      evaluated. RESULTS: Twenty-four male and 16 female patients aged 12 years to 70
      (SD) (mean 35 +/- 12 years) were operated on and followed for 17.8 +/- 8.7
      months. Preoperatively, best corrected visual acuity (BCVA) was less than 20/40
      in all patients, which improved to 20/40 or better after surgery. Twenty-two eyes
      (53.6%) achieved BCVA of 20/20. The major cause of postoperative visual acuity
      less than 20/20 was vitreous haze. There were no major intraoperative
      complications. Postoperatively, mild anterior chamber fibrin reaction occurred in
      4 patients (9.7%), IOL deposits occurred in 11 eyes (26.8%), and decentration was
      observed in 1 eye. During follow-up, 6 eyes (14.6%) developed posterior capsule
      opacification requiring a neodymium:YAG (Nd:YAG) laser capsulotomy. There was 1
      case of clinical cystoid macular edema that resolved with medication. There were
      no cases of posterior synechias, postoperative glaucoma, or retinal detachment.
      CONCLUSION: Phacoemulsification with PC IOL implantation is a safe procedure with
      good visual outcomes in patients with FHIC and cataract.

PMID- 15975469
TI  - Intraoperative complications of phacoemulsification in eyes with and without
      pseudoexfoliation.
AB  - PURPOSE: To determine the intraoperative complications in a large series of
      phacoemulsification procedures, including patients with and without
      pseudoexfoliation, excluding those with marked phacodonesis or lens subluxation.
      SETTING: Department of Ophthalmology, Carmel Medical Centre, Haifa, Israel.
      METHODS: This institutional case-control study included 1501 consecutive
      phacoemulsification procedures: 137 eyes with pseudoexfoliation and 1364 eyes
      without this condition. Baseline demographics and clinical factors were collected
      from the medical files. A comparative analysis of the incidence of intraoperative
      complications in eyes with or without pseudoexfoliation was calculated.
      Univariate analysis and multiple logistic regression were used to identify ocular
      factors that predicted intraoperative complications. RESULTS: There was no
      significant difference (P>.05) in the rate of intraoperative complications
      between the pseudoexfoliation (5.8%) and control (4.0%) groups. There were no
      significant differences in the incidence of capsular breaks, vitreous loss, and
      zonular ruptures without vitreous loss in the 2 groups. Pseudoexfoliation did not
      confer a statistically higher risk for intraoperative complications (odds ratio
      1.62, 95% confidence interval 0.74-3.55). CONCLUSION: Phacoemulsification by
      experienced surgeons is safe in eyes with pseudoexfoliation without marked
      phacodonesis or lens subluxation.

PMID- 15975470
TI  - Signal quality of biometry in silicone oil-filled eyes using partial coherence
      laser interferometry.
AB  - PURPOSE: To assess the practical feasibility and signal quality of axial length
      measurements by partial coherence laser interferometry in silicone oil-filled
      eyes with previous complicated vitreoretinal surgery. SETTINGS: Department of
      Ophthalmology, University Cologne, Cologne, Germany. METHODS: Using a Zeiss
      IOLMaster, axial length measurements and signal-to-noise ratios of optical
      biometry in silicone oil-filled eyes (n=45) and contralateral eyes without
      tamponade (n=41) were analyzed. RESULTS: Axial length measurements with signal-to
      noise ratio > or =2 were feasible in 41 of 45 silicone oil-filled eyes (91%) and
      37 of 41 eyes without tamponade (90%). Cataract, central retinal detachment,
      vitreous hemorrhage, and emulsified oil droplets attached to the intraocular lens
      were reasons for failure of partial coherence laser interferometry. The signal-to
      noise ratio of the first 2 measurements was significantly smaller (P=.04) in
      silicone-filled eyes (4.4 +/- 2.0) than in eyes without tamponade (5.5 +/- 3.0).
      Axial lengths of the oil-filled eye and the contralateral eye showed a
      significant intraindividual correlation (P<.0001, Spearman r=0.84). CONCLUSIONS:
      Partial coherence laser interferometry shows good clinical practicability in
      silicone oil-filled eyes with previous complicated vitreoretinal surgery. Further
      studies are needed to assess the reliability of these measurements with regard to
      postoperative refraction after combined oil removal and cataract surgery.

PMID- 15975471
TI  - Incidence of intraoperative complications during phacoemulsification in
      vitrectomized and nonvitrectomized eyes: prospective study.
AB  - PURPOSE: To compare the incidence of intraoperative complications during
      phacoemulsification surgery in patients with and without prior pars plana
      vitrectomy (PPV). SETTING: Department of Ophthalmology, Norfolk, and Norwich
      University Hospital, Norwich, United Kingdom. METHODS: Prospective collection of
      operative complications in 2000 consecutive cataract extractions performed by 1
      surgeon (R.L.B.). Details of all patients who had intraoperative complications
      including age at operation and sex were recorded. It was also noted whether the
      eye previously PPV. Complications recorded were posterior capsule rupture (PCR)
      with and without vitreous loss, iris trauma, loss of nuclear fragment into
      vitreous, and choroidal hemorrhage. RESULTS: Of 2000 eyes, 117 had previous PPV.
      Of these, there were 2 (1.70%) cases of PCR. There were no cases of iris trauma,
      choroidal hemorrhage, or dropped nucleus fragments into the posterior chamber.
      Nonvitrectomized eyes totaled 1883. Rates of complications were as follows: PCR
      without vitreous loss, 0.16%; PCR with vitreous loss, 0.53%; iris trauma, 0.16%;
      choroidal hemorrhage, 0.16%; and dropped nucleus fragment in the vitreous, 0.11%.
      CONCLUSION: Despite well-known difficulties encountered in vitrectomized eyes
      such as zonular damage, increased mobility of the lens-iris diaphragm, and
      altered intraocular fluid dynamics, the incidence of intraoperative complication
      rates is similar to nonvitrectomized eyes in the hands of an experienced surgeon.

PMID- 15975472
TI  - Ultrasonic power reduction during phacoemulsification using adjunctive NeoSoniX
      technology.
AB  - PURPOSE: To compare the phacoemulsification times and powers used in 3
      phacoemulsification machine configurations. SETTING: Wolfe Eye Clinic,
      Marshalltown, Iowa, USA. METHODS: A randomized prospective study of 410
      consecutive cases was conducted. All cases were performed using the Alcon Legacy
      20000 phacoemulsification machine. Configurations were the Standard Legacy 20000
      machine (n=165), Advantec upgraded Legacy 20000 (n=112), and Advantec upgraded
      Legacy 20000 with NeoSoniX (n=133). Preoperative measurements included the
      patient's age and cataract grade using the nuclear color (NC) scale of the Lens
      Opacities Classification System III (LOCS III). Intraoperative measurements
      included machine-measured phacoemulsification time and average percentage of
      maximum power expenditure. An independent statistician performed analysis of
      covariance on NC for each of the machine configurations. RESULTS: The mean age in
      years and the NC value were similar in each group. There was no significant
      difference in phacoemulsification time in minutes among the 3 machines:
      Standard=1.17, Advantec=1.12, NeoSoniX=1.16. The average percentage of maximum
      power consumption was similar for Standard Legacy 20000 at 38.00% and Advantec
      Legacy 20000 at 37.97% but significantly less for Advantec Legacy 20000 with
      NeoSoniX at 27.56% (P<.001). With the NeoSoniX-incorporated machine, compared
      with Standard and Advantec, a 27.5% reduction in ultrasonic energy power
      expenditure was observed all grades of nuclear density. CONCLUSIONS: The addition
      of 15% amplitude NeoSoniX rotational energy reduced total ultrasonic power
      expenditure by 27.5% for all cataract nuclear densities.

PMID- 15975473
TI  - Reliability of a new correcting factor in calculating intraocular lens power
      after refractive corneal surgery.
AB  - PURPOSE: To test the reliability of a corneal radius correcting factor (R factor)
      in calculating intraocular lens (IOL) power in eyes that developed cataract after
      refractive surgery and compare it with the clinical history (CHM) and double-K
      (DKM) methods. SETTING: Department of Ophthalmology, Second University of Naples,
      Naples, Italy. METHODS: Nineteen eyes from the literature that underwent cataract
      extraction and IOL implantation after refractive surgery were used to compare
      actual postoperative and expected refractive errors utilizing the R factor, CHM,
      and DKM. Intraocular lens powers were calculated with 3 formulas: SRK/T, Hoffer Q
      and Holladay 1. The differences were evaluated with the Wilcoxon test and
      Spearman correlation. RESULTS: With the R factor SRK/T and Holladay 1 formulas
      gave the best results; 16 (84.2%) and 17 (89.5%) eyes were within +/-2 diopters
      (D) of emmetropia. With CHM, the best results were obtained using the SRK/T and
      Holladay 1 formulas; with both formulas 12 (63.2%) eyes were within +/-2 D of
      emmetropia. With DKM, the best results were obtained using SRK/T and Holladay 1
      formulas; with both formulas 10 eyes (52.63%) were in the range of +/-2 D from
      emmetropia. CONCLUSIONS: The R factor can be used with the SRK/T or Holladay 1
      formula because this method seems comparable or superior to DKM and CHM.

PMID- 15975474
TI  - Repeatability of autorefraction and axial length measurements after laser in situ
      keratomileusis.
AB  - PURPOSE: To assess the repeatability and agreement of refractive error
      measurements and the repeatability of axial length (AL) measurements in patients
      after laser in situ keratomileusis (LASIK). SETTING: The Ohio State University
      College of Optometry, Columbus, Ohio, USA. METHODS: Subjective refraction,
      autorefraction measurements with the Grand Seiko and Humphrey autorefractors, and
      AL measurements with the IOLMaster were completed for 40 previously myopic LASIK
      patients under noncycloplegic and cycloplegic conditions on 2 separate occasions.
      RESULTS: The mean difference between visits for axial length measurements was
      0.008 mm +/- 0.04 (SD). The between visits repeatability for all refractive error
      measurements were <0.75 diopter (D). The mean difference between the subjective
      refraction and the Humphrey autorefractor for spherical equivalent was
      statistically significant under noncycloplegic conditions (-0.90 D, P<.0001) and
      cycloplegic conditions (-2.05 D, P<.0001). The mean difference between subjective
      refraction and Grand Seiko autorefraction measurements was not significant under
      noncycloplegic conditions (+0.05 D, 95% limits of agreement [LoA]=-0.99, 1.09;
      P=.52) conditions but was statistically significant, but not clinically relevant,
      under cycloplegic conditions (+0.17 D, 95% LoA=-0.73, 1.07; P=.03). CONCLUSIONS:
      Refractive error measurements after LASIK using the Grand Seiko autorefractor are
      reliable and agree well with subjective refraction measurements.

PMID- 15975475
TI  - Assessment of nerve fiber layer thickness before and after laser in situ
      keratomileusis using scanning laser polarimetry with variable corneal
      compensation.
AB  - PURPOSE: To determine the effect of laser in situ keratomileusis (LASIK) on
      retinal nerve fiber layer (RNFL) thickness measurements obtained by scanning
      laser polarimetry with variable corneal compensation (SLP-VCC). SETTING: Gimbel
      Eye Centre, Calgary, Alberta. METHODS: Retinal nerve fiber layer thickness
      measurements were performed in both eyes of 25 consecutive healthy patients the
      day of LASIK surgery and 1 month after by trained examiners using the GDx-VCC
      nerve fiber analyzer. Thickness measurements and all other parameters provided by
      the software of the machine before and after LASIK were analyzed using the paired
      Student t test. RESULTS: Mean age of the patients was 39 years +/- 9.6 (SD)
      (range 24 to 57 years). The mean preoperative spherical equivalent was -4.15 +/-
      1.76 diopters (D) (range -1.0 to -7.50 D) and the mean postoperative spherical
      equivalent, 0.12 +/- 0.39 D (range -0.75 to +1.00 D). Mean ablation depth was 62
      +/- 23 mum. No statistically significant difference was found in SLP parameters
      after LASIK (P<.05). No clinically significant difference in RNFL thickness
      measurements was noted in any eye. CONCLUSION: These data suggest that SLP-VCC
      mean thickness measurements are not influenced by LASIK-induced alterations in
      corneal architecture. Measurements obtained with SLP-VCC before surgery may be
      used for future comparisons.

PMID- 15975476
TI  - Scanning laser polarimetry of nerve fiber layer thickness in normal eyes after
      cataract phacoemulsification and foldable intraocular lens implantation.
AB  - PURPOSE: To assess the effect of cataract phacoemulsification and intraocular
      lens (IOL) implantation on retinal nerve fiber layer (RNFL) thickness using
      scanning laser polarimetry (SLP). SETTING: Eye Clinic, Trieste University, Italy.
      METHODS: Forty-eight eyes were evaluated prospectively the day before and 30 days
      after cataract phacoemulsification and foldable IOL implantation. In each eye,
      lens opacity grading according to the Lens Opacities Classification System III
      (LOCS III), and axial length (AL) measurements were performed. Retinal nerve
      fiber layer thickness was quantified at baseline by means of SLP and anterior
      segment birefringence compensation was evaluated acquiring macular retardation
      map (MRM). Acrylic and silicone IOLs were implanted randomly. After surgery, RNFL
      thickness was reevaluated, and MRM was reacquired. Macular retardation map
      pattern variations regarding baseline profile were classified into 3 groups: no
      variation, bow-tie profile enhancement, or attenuation. Distribution of IOL
      power, AL, and cataract type in the 3 groups was assessed, as were presurgery and
      postsurgery SLP parameters with mean values (+/-SD) compared by paired t test.
      RESULTS: Twenty-two eyes (Group 1, 45.8%) showed no MRM variation, 14 (Group 2,
      29.2%) an enhancement, and 12 (Group 3, 25%) an attenuation. In Group 1, no
      significant RNFL thickness variation occurred. In Group 2, variation 10% to 15%
      was measured, whereas thickening a 8% to 15% thinning appeared in Group 3.
      Variations occurred irrespective of IOL material, AL, or cataract type.
      CONCLUSIONS: Cataract surgery with IOL implantation was associated with an MRM
      profile change and RNFL thickness variations in 54.2% of eyes. Variations are
      probably related to opacified lens removal. A new baseline SLP reading is
      mandatory after cataract surgery.

PMID- 15975477
TI  - In vitro influence of vancomycin on adhesion of a Staphylococcus epidermidis
      strain encoding intercellular adhesion locus ica to intraocular lenses.
AB  - PURPOSE: To assess anti-adhesion and/or bactericidal properties of vancomycin in
      vitro and to determine when these effects are detectable to estimate its
      relevance to perioperative antibiotic prophylaxis and analyze the efficacy of a
      newly designed vancomycin insert prototype for endophthalmitis prevention.
      SETTING: University research laboratory, Lyon, France. METHODS: Staphylococcus
      epidermidis clinical strain N890074 containing the intercellular adhesion locus
      ica was used as the infectious agent. Vancomycin was used at 20 microg/mL. A
      sterile biocompatible, biodegradable vancomycin insert, releasing 230 microg of
      antibiotics over 100 minutes, was designed especially for this study. To obtain
      bacterial killing curves, experiments were first performed in a 103 colony
      forming units (CFU/mL) bacterial suspension containing no intraocular lenses
      (IOL). Then IOLs were incubated in the suspension, and bacterial adherence was
      determined using bacterial counting with and without antibiotic. RESULTS:
      Vancomycin (solution and insert) had an anti-adhesion effect after 1 hour and a
      relevant bactericidal effect after 6 hours of incubation. CONCLUSIONS: Vancomycin
      used with irrigating solutions does not remain in the anterior chamber long
      enough to develop bactericidal effect. Even if it initially reduces bacterial
      adhesion, used at a drug level dropping below the bacterial minimal inhibitory
      concentration, it could result in a secondary increase of the adhesion of slime
      producing bacteria. A sufficiently high concentration was obtained in vitro by
      the new sustained-release system, thereby overcoming the theoretical drawback of
      a short half-life within the anterior chamber. Anti-adhesion and bactericidal
      action of vancomycin inserts remains to be confirmed in clinical studies.

PMID- 15975478
TI  - Octreotide inhibits growth factor-induced and basal proliferation of lens
      epithelial cells in vitro.
AB  - PURPOSE: To evaluate whether a synthetic analog of somatostatin, octreotide, has
      an inhibitory effect on lens epithelial cell (LEC) proliferation induced by basal
      and basic fibroblast growth factor as well as insulin-like growth factor 1.
      METHODS: Confluent LEC cultures were kept in serum-free defined medium containing
      [(3)H]-thymidine in the presence of octreotide alone at the concentration range
      of 10(-7) M to 10(-10) M or in combination with either basic fibroblast growth
      factor or insulin-like growth factor 1. Additionally, the expression of
      somatostatin receptors (1-5) in LECs were analyzed by reverse transcription
      polymerase chain reaction. RESULTS: Octreotide decreased the proliferation of
      human LECs in a dose-dependent manner, exhibiting a maximal inhibitory
      concentration at 10(-9) M (P<.03). Moreover, octreotide (10(-9) M) potently
      inhibited basic fibroblast growth factor- and insulin-like growth factor 1
      induced bovine lens epithelial cell proliferation (P<.0001). The respective
      products of all 5 subtypes of somatostatin receptors were found in human LECs and
      somatostatin receptor type 2 in bovine LECs. CONCLUSION: The data show that,
      depending on the concentration, octreotide is able to decrease proliferative
      responses of LECs. Moreover, the cell proliferation induced by growth factors was
      potently inhibited by octreotide. Therefore, octreotide could be a potential drug
      after cataract surgery in prevention of growth factor-dependent proliferative
      disorders such as posterior capsule opacification and anterior capsule
      contraction in diabetic patients.

PMID- 15975479
TI  - Effects of topical tranilast on corneal haze after photorefractive keratectomy.
AB  - PURPOSE: To determine whether topical tranilast might reduce corneal haze through
      suppression of transforming growth factor (TGF)-beta1 synthesis in keratocyte
      after photorefractive keratectomy. SETTING: Department of Ophthalmology, Korea
      University College of Medicine, Seoul, Republic of Korea. METHODS:
      Photorefractive keratectomy was performed on 48 eyes of 28 white rabbits and 24
      eyes in a tranilast group were treated with tranilast solution, and the other 24
      eyes in control group were treated with saline after laser ablation. The grades
      of corneal haze at 1, 2, 4, and 8 weeks after surgery were evaluated in 10 eyes
      of each group for comparison. Immunohistochemistry was performed on 10 eyes of
      each group, and Western blot analysis was done on 4 eyes of each group for
      studying TGF-beta1 expression at postoperative day 7. RESULTS: There was no
      statistically significant difference in corneal haze between 2 groups from week 1
      to week 4 after surgery, but a significant difference was found at week 8 after
      photorefractive keratectomy (P=.02). The mean number of keratocytes that
      expressed TGF-beta1 in the tranilast group was 58.3 (+/-17.2), which showed
      significant difference, compared with that of the control group, 104.5 (+/-23.0)
      (P<.01). Western blot analysis also revealed that the amount of TGF-beta1 in
      tranilast group was slightly less than the control group. CONCLUSIONS: Topical
      tranilast could reduce corneal haze by suppressing TGF-beta1 expression in
      keratocytes after photorefractive keratectomy.

PMID- 15975480
TI  - Low acute endophthalmitis rate: possible explanations.

PMID- 15975481
TI  - Clear corneal paracentesis: a case of chronic wound leakage in a patient having
      bimanual phacoemulsification.

PMID- 15975482
TI  - Neodymium:YAG laser sweeping of the posterior surface of an intraocular lens.

PMID- 15975483
TI  - Nucleofractis sequence for inexperienced phacoemulsification surgeons.

PMID- 15975484
TI  - Plasma pyridoxal 5'-phosphate is a significant indicator of immune responses in
      the mechanically ventilated critically ill.
AB  - OBJECTIVES: This study assessed the effect of vitamin B6 status on immune
      responses in mechanically ventilated, critically ill patients and compared the
      results with those of healthy controls. METHODS: This was designed as a cross
      sectional observational study. Forty patients in the intensive care unit
      successfully completed this study. Vitamin B6 intake was recorded for 8 d.
      Severity of illness (Second Acute Physiology and Chronic Health Evaluation score)
      was recorded. Thirty-eighty healthy controls were recruited from the physical
      check unit of Taichung Veterans General Hospital (Taichung, Taiwan). All control
      subjects were given instruction on how to complete a 24-d diet recall. Vitamin B6
      status was assessed by direct measures (plasma pyridoxal 5'-phosphate [PLP] and 4
      pyridoxic acid) and indirect measures (erythrocyte alanine and aspartate
      aminotransferase activity coefficients). Levels of serum albumin, hemoglobin,
      hematocrit, high-sensitivity C-reactive protein, and immune responses (white
      blood cell, neutrophil, total lymphocytes, T lymphocytes [CD3], B lymphocytes
      [CD19], T-helper cells [CD4], and suppressor cells [CD8]) were determined.
      RESULTS: Critically ill patients had sufficient vitamin B6 intake but showed
      marginal PLP deficiency (20.9 +/- 1.5 nmol/L). In addition, critically ill
      patients had significantly lower and abnormal immune responses than did healthy
      controls. There was no significant correlation of vitamin B6 intake and
      erythrocyte alanine and aspartate aminotransaminase activity coefficients with
      immune indices. Plasma PLP concentration was strongly negatively correlated with
      high-sensitivity C-reactive protein level. However, plasma PLP was significantly
      associated with immune responses after adjustment for age, sex, high-sensitivity
      C-reactive protein, and the other four vitamin B6 indicators. CONCLUSIONS: Plasma
      PLP is a significant indicator of immune responses in human subjects. Further
      research is warranted to study whether vitamin B6 supplementation in critically
      ill patients improves their immune responses.

PMID- 15975485
TI  - Variation in enteral nutrition delivery in mechanically ventilated patients.
AB  - OBJECTIVE: We determined the variability in enteral feeding practices in
      mechanically ventilated patients in four adult intensive care units of a tertiary
      care, referral hospital. METHODS: Patients who had been mechanically ventilated
      for at least 48 h and received enteral nutrition were prospectively followed.
      RESULTS: Fifty-five of 101 consecutive mechanically ventilated patients received
      enteral nutrition; in 93% of patients, feedings were infused into the stomach.
      Patients who were cared for in the medical intensive care unit, where a
      nutritional protocol was operational, received enteral nutrition earlier in their
      ventilatory course (P=0.004) and feedings were advanced to target rates faster
      (P=0.043) than those who received care in other units. The number (P=0.243) and
      duration (P=0.668) of interruptions in feeding did not differ by patient
      location. On average, patients received only 50% to 70% of their targeted caloric
      goals during the first 6 days of enteral nutrition. Most feeding discontinuations
      (41%) were secondary to procedures. Gastrointestinal intolerances, including
      vomiting, aspiration, abdominal distention, and increased gastric residuals, were
      uncommon despite allowing gastric residuals up to 300 mL. CONCLUSIONS: The
      practice of providing enteral feeds to mechanically ventilated patients varies
      widely, even within one hospital. A protocol enhanced early initiation of enteral
      feeds and advancement to target feeding rates but did not alter the number or
      duration of interruptions in enteral feedings. Procedures represented the most
      common reason for stopping enteral feeds, and gastrointestinal intolerances
      (vomiting, aspiration, and increased gastric residuals) caused few feeding
      interruptions. The gastric route was safe and well tolerated for early enteral
      feeding in most mechanically ventilated patients.

PMID- 15975486
TI  - Circulating ghrelin in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Unexplained weight loss is common in patients with chronic obstructive
      pulmonary disease (COPD). Because ghrelin plays an important role in energy
      homeostasis, this study investigated the plasma level of ghrelin in COPD.
      METHODS: Plasma ghrelin levels and levels of leptin, tumor necrosis factor-alpha,
      and C-reactive protein were measured in 29 patients with COPD and 17 healthy
      controls. Body composition was assessed with bioelectrical impedance analysis.
      RESULTS: Body mass index and percentage of body fat were lower in patients who
      had COPD than in healthy controls. Plasma ghrelin and leptin concentrations were
      significantly lower in patients who had COPD than in healthy controls (ghrelin:
      0.25+/-0.22 ng/mL versus 0.43+/-0.24 ng/mL, P=0.013; leptin: 1.77+/-0.70 ng/mL
      versus 2.85+/-0.96 ng/mL, P=0.000). In contrast, tumor necrosis factor-alpha and
      C-reactive protein were significantly higher in those with COPD than in controls.
      Plasma ghrelin (log transformed) was positively correlated with body mass index
      and percentage of body fat in patients with COPD but negatively correlated in
      control subjects. Plasma ghrelin was negatively correlated with tumor necrosis
      factor-alpha and C-reactive protein in COPD. CONCLUSION: Plasma ghrelin level was
      decreased in COPD and this is different from other weight-loss diseases. These
      data suggest that decreased ghrelin and other factors may contribute to
      alterations in metabolic status during inflammatory stress in this disease.

PMID- 15975488
TI  - Early cardiovascular changes in 10- to 15-year-old stunted children: the
      Transition and Health during Urbanization in South Africa in Children study.
AB  - OBJECTIVE: Early changes in vascular function could be associated with stunting,
      which may contribute to the development of cardiovascular diseases in later life.
      In this study we tested the hypothesis that stunting may be related to changes in
      cardiovascular function in African children ages 10 to 15 y. METHODS: In the
      Transition and Health during Urbanization in South Africa in Children study, the
      health status of children in the North-West Province of South Africa was studied.
      It was an epidemiologic, cross-sectional study in which 583 black non-stunted and
      192 stunted children (stature below the fifth percentile for age) of both sexes
      ages 10 to 15 y were recruited from 44 schools. Blood pressure was monitored with
      the Finapres (finger-arterial pressure) apparatus and by means of the Fast
      Modelflo software program; measurements for systolic and diastolic blood
      pressure, mean arterial pressure, pulse pressure, heart rate, cardiac output,
      stroke volume, total peripheral resistance, and arterial compliance were
      obtained. Dietary intake data were collected with a 24-h dietary recall
      questionnaire. Nutrient coding was the same for all recalls and macro- and
      micronutrients were calculated. Anthropometric measurements were done according
      to standard methods. RESULTS: There were no significant differences in systolic
      blood pressure and diastolic blood pressure between stunted and non-stunted
      children after correction for body mass index and heart rate. Stroke volume,
      arterial compliance, and cardiac output were significantly lower and total
      peripheral resistance was significantly higher in stunted children than in non
      stunted children. No significant differences in dietary intake could be detected,
      although dietary intakes were slightly lower in the stunted children.
      CONCLUSIONS: We found that compliance, a marker of vascular function, is
      significantly lower in stunted children. Stunting was related to early changes in
      cardiovascular function in African children ages 10 to 15 y.

PMID- 15975489
TI  - Evaluation of a foot-to-foot impedance meter measuring extracellular fluid volume
      in addition to fat-free mass and fat tissue mass.
AB  - OBJECTIVES: The first objective was to compare the accuracy of a foot-to-foot
      impedance meter with a multifrequency bioimpedance for measurements of fat-free
      mass (FFM) and fat mass (FM) using dual energy X-ray absorptiometry (DXA) as
      reference. The second objective was to validate measurements of extracellular
      water resistance and volume by the foot-to-foot impedance meter, using
      multifrequency bioimpedance as reference. METHODS: This investigation was carried
      out in 60 volunteers 18 to 71 y of age. Impedance meters were a Tefal Bodymaster
      Vision (foot-to-foot) that featured a square wave signal and a Xitron Hydra 4200
      (5 to 1000 kHz) by using the bioimpedance spectroscopic method. RESULTS: Bland
      Altman tests showed that FFM differences between Tefal and DXA data were 1.98 +/-
      3.09 kg in men and -0.08+/-2.98 kg in women. Total body water was measured by the
      Xitron, and FFM as measured with the Xitron was calculated as total body water
      divided by 0.732. Mean differences between Xitron-measured and DXA-measured FFM
      were 2.37+/-3.03 kg for men and 2.84+/-2.40 kg for women, indicating a systematic
      underestimation by the Xitron of intracellular volume. Extracellular water
      resistances measured by Tefal were in good agreement with those measured by
      Xitron with electrodes pasted under the subject's feet (mean difference 8.5+/-31
      Omega). Extracellular water volumes were calculated from Tefal-measured
      extracellular water resistances by using a modified bioimpedance spectroscopic
      method and differed from those measured with Xitron by-0.03+/-0.66 L. CONCLUSION:
      Limits of agreement with DXA-measured FFM produced by the foot-to-foot impedance
      meter tested are too large for clinical measurements in individuals, but they are
      sufficient to assess FFM in groups of subjects and for home use. Our prototype
      was also capable of estimating extracellular water volume with a similar accuracy
      as multifrequency bioimpedance in normal subjects.

PMID- 15975487
TI  - Early enteral administration of immunonutrition in critically ill children:
      results of a blinded randomized controlled clinical trial.
AB  - OBJECTIVES: In a blinded, prospective, randomized, controlled clinical trial, we
      compared nitrogen balance (NB), nutritional indices, antioxidant catalysts, and
      outcome in critically ill children given an immune-enhancing formula (I) or
      conventional early enteral nutrition (C). METHODS: Fifty patients, 103 +/- 7
      months old, with disorders prompting admission to the pediatric intensive care
      unit, including sepsis, respiratory failure, and severe head injury, were
      enrolled in the study. Within 12 h of admission, patients were randomized to
      receive I (n=25) or C (n=25). Caloric intake was aimed at meeting patient's
      predicted basal metabolic rate by day 2 and predicted energy expenditure by day
      4, irrespective of group assignment. Outcome endpoints and complications were
      recorded; NB, transthyretin, retinol-binding protein, transferrin, zinc, copper,
      and metabolic indices were measured on days 1 and 5 and compared with clinical
      and nutritional characteristics within and between groups. RESULTS: Both diets
      achieved their initial targets of covering predicted basal metabolic rate by day
      2 and predicted energy expenditure by day 4. Twenty four-hour NB became positive
      in 40% of patients in group C and occurred in 64% of patients in group I by day
      5. Only in group I did the mean NB become positive by day 5 (0.07+/-0.07 g/kg
      versus -0.24+/-0.03 g/kg on day 1, P<0.001) compared with group C in which the
      mean NB remained negative (-0.06+/-0.04 g/kg versus -0.25+/-0.06 g/kg on day 1,
      P<0.001). By day 5, nutritional indices and antioxidant catalysts showed a higher
      increasing trend in group I compared with group C and higher osmolality (P<0.02),
      sodium (P<0.03), and urea (P<0.04). Diarrhea for group I (P<0.02) and gastric
      distention for group C (P<0.04) were the most frequently recorded complications.
      Mortality or length of stay did not differ between groups, but there was a trend
      for less gastric gram plus isolates (P<0.05) or for Candida species (P<0.04) and
      nosocomial infections in group I compared with group C. CONCLUSIONS: Although
      less well tolerated, immunonutrition is a feasible method of early enteral
      nutrition in the pediatric intensive care unit. It has a favorable effect on
      nutritional indices and antioxidant catalysts, but not on outcome hard endpoints.
      Although it poses a higher metabolic burden to the patient, it shows a trend to
      improve colonization and infection rates. Appropriate modifications for specific
      age populations might improve its tolerability and benefits among critically ill
      children.

PMID- 15975490
TI  - Effects of a medium-chain triacylglycerol/long-chain triacylglycerol fat emulsion
      containing a reduced ratio of phospholipid to triacylglycerol in pediatric
      surgical patients.
AB  - OBJECTIVE: Medium-chain triacylglycerol (MCT) has been shown to provide better
      nutritional support than long-chain triacylglycerol (LCT). We compared the
      efficacy of MCT/LCT fat emulsions containing a usual (0.12) or a decreased (0.06)
      ratio of phospholipid to triacylglycerol (PL:TG) in pediatric patients under
      surgical stress. METHODS: Three patient groups (n=10 in each) received equivalent
      amounts of glucose (12 g.kg(-1).d(-1)) and amino acids (2 g.kg(-1).d(-1)), but
      group A received a 10% MCT fat emulsion (PL:TG 0.06), group B received a 20% MCT
      fat emulsion (PL:TG 0.06), and group C received a 10% MCT/LCT fat emulsion (PL:TG
      0.12) in amounts of 1.5 g.kg(-1).d(-1) in a randomized study. Total parenteral
      nutrition was given for 7 d. Blood samples were collected before total parenteral
      nutrition administration and on days 4 and 7 for determination of various
      biochemical indexes. RESULTS: Serum phospholipid concentrations were
      significantly higher in group C than in group A or B on days 4 and 7 (P<0.05).
      Serum triacylglycerol and cholesterol concentrations and the very-low-density
      lipoprotein percentage were also significantly higher in group C than in group A
      or B on days 4 and 7 (P<0.05). The high-density lipoprotein percentage was
      significantly higher in group B on days 4 and 7 (P<0.05). CONCLUSIONS: In
      pediatric patients under surgical stress, a total parenteral nutrition regimen
      containing an MCT/LCT fat emulsion with a decreased PL:TG ratio (0.06) is likely
      to result in partly better lipid and lipoprotein metabolism than an emulsion
      containing the usual ratio (0.12).

PMID- 15975491
TI  - Rapidly exchangeable pool study of zinc in free-living or institutionalized
      elderly women.
AB  - OBJECTIVE: We evaluated the effect of age and institutionalization on zinc
      metabolism by using a stable isotope technique. METHODS: This was a randomized
      case-control study. Three groups were recruited: nine young women (group 1, ages
      36+/-1 y) as controls, nine free-living elderly women (group 2, ages 72+/-2 y),
      and nine institutionalized women (group 3, ages 73+/-2 y). Only women were
      recruited to obtain homogeneous groups. The study was set in a Valence hospital
      (France) in the geriatric department (headed by Dr. Ferry). The experimental
      design of the study was reviewed and approved by the local ethical committee, and
      all participants signed a consent form. No subject dropped out of the study. A
      zinc stable isotope label (0.73 mg of (70)Zn) was injected intravenously into
      patients and measured by inductively coupled plasma mass spectrometry. RESULTS:
      Decay curves of the plasma (70)Zn followed a one-compartment kinetic leading to
      the determination of one pool. The size of this pool suggested that it
      corresponded to the liver compartment. The size of this pool was significantly
      smaller in elderly people. (70)Zn plasma resident time was significantly longer
      in elderly individuals, and shorter in institutionalized than in free-living
      elderly subjects. CONCLUSION: These data suggest that the zinc metabolism of
      elderly women is related to lifestyle or its consequences and to age. Moreover,
      we have demonstrated that kinetic studies using stable isotopes of zinc can
      provide novel information on exchangeable zinc pools in clinical situations.

PMID- 15975492
TI  - Short-chain fatty acids alter tight junction permeability in intestinal monolayer
      cells via lipoxygenase activation.
AB  - OBJECTIVE: Involvement of lipoxygenase (LOX) and cyclo-oxygenase (COX) on
      cellular differentiation or apoptosis induced by butyrate has been reported
      recently, but the effect on tight junction (TJ) permeability has not been
      reported. One major activity of butyrate and, to a lesser extent, propionate is
      to modulate gene transcription via histone acetylation by their histone
      deacetylase inhibitor activity. In this study, we evaluated the activation of LOX
      and COX in TJ permeability changes by short-chain fatty acids, butyrate,
      propionate, and acetate in intestinal monolayer cells and their possible
      mechanism by histone acetylation. METHODS: The effects of LOX and COX inhibitors
      on TJ permeability and the expression of LOX or COX mRNA induced by short-chain
      fatty acids were investigated in Caco-2 cells using Transwell chambers. The
      effects of hydroxyeicosatetraenoic acid (a product of LOX) on TJ permeability
      were also evaluated. The effects of short-chain fatty acids were compared with
      those of trichostatin A (histone deacetylase inhibitor). RESULTS: A LOX inhibitor
      clearly inhibited the effect of butyrate on TJ permeability, whereas COX
      inhibitors did not. The LOX and COX inhibitors partly inhibited the effects of
      propionate but not of acetate. Butyrate increased LOX mRNA expression, and
      hydroxyeicosatetraenoic acid and trichostatin A mimicked its effect. CONCLUSION:
      These results suggest that short-chain fatty acids, especially butyrate, induce
      TJ permeability changes through LOX activation through histone acetylation.

PMID- 15975493
TI  - Effects of a nutritional supplement containing Salacia oblonga extract and
      insulinogenic amino acids on postprandial glycemia, insulinemia, and breath
      hydrogen responses in healthy adults.
AB  - OBJECTIVE: This study evaluated the postprandial glycemic, insulinemic, and
      breath hydrogen responses to a liquid nutritional product containing Salacia
      oblonga extract, an herbal alpha-glucosidase inhibitor, and two insulinogenic
      amino acids. METHODS: In a randomized, double-masked, crossover design, 43
      healthy subjects were fed the following meals on separate days after overnight
      fasting: control (C; 480 mL of a study beverage containing 82 g of carbohydrate,
      20 g of protein, and 14 g of fat), control plus 3.5 g each of phenylalanine and
      leucine (AA), control plus 1000 mg of S. oblonga extract (S), and control plus S
      and AA (SAA). Postprandially, fingerstick capillary plasma glucose and venous
      serum insulin levels were measured for 180 min, and breath hydrogen excretion was
      measured for 480 min. RESULTS: The baseline-adjusted peak glucose response was
      not different across meals. However, changes in plasma glucose areas under the
      curve (0 to 120 min and 0 to 180 min, respectively) compared with C were -9% and 
      11% for AA (P>0.05 each), -27% and -24% for S (P=0.035 and 0.137), and -27% and 
      29% for SAA (P<0.05 each). Changes in insulin areas under the curve were +5% and
      +5% for AA (P>0.05 each), -35% and -36% for S (P<0.001 each), and -6% and -7% for
      SAA (P>0.05 each). Breath hydrogen excretion was 60% greater (P<0.001) in the S
      containing meals than in the C- and AA-containing meals and was associated with
      mild flatulence. CONCLUSIONS: Salacia oblonga extract is a promising
      nutraceutical ingredient that decreased glycemia in this study. Supplementation
      with amino acids had no significant additional effect on glycemia.

PMID- 15975494
TI  - Gender effects in dietary histidine-induced anorexia.
AB  - OBJECTIVE: Histamine, a derivative of histidine, decreases food intake by
      activation of histamine neurons. The aim of the present study was to clarify
      gender-related differences in food intake through the histidine-histamine neuron
      system. METHODS: Male, female, and ovariectomized rats were fed a histidine
      enriched diet or a control diet with the cafeteria method. RESULTS: The
      suppressive effect of histidine on food intake was greater in female rats than in
      male rats, and the suppressive effect of histidine on food intake was less in
      ovariectomized rats than in female rats. CONCLUSION: Our results indicate that
      females are more sensitive than males to dietary histidine-induced anorexia.

PMID- 15975495
TI  - Preoperative feeding preserves heart function and decreases oxidative injury in
      rats.
AB  - OBJECTIVE: The nutritional status of a patient has been implicated as an
      important factor in the development of postoperative complications. Fasting
      before an operation may have detrimental effects on the metabolic state. We
      hypothesized that there was a positive correlation between preoperative
      nutritional status and postoperative organ function. METHODS: Preoperative
      feeding was compared with fasting with respect to effects on organ function and
      biochemical parameters in an animal model of extensive large abdominal surgery.
      Male Wistar rats were fed ad libitum or fasted for 16 h, after which the arteria
      mesenterica superior was clamped for 60 min followed by 180 min of reperfusion.
      RESULTS: After the ischemic period, heart function was significantly better in
      animals that were fed ad libitum than in fasted animals. Moreover, after
      intestinal ischemia and reperfusion, fed rats showed significantly higher levels
      of intestinal adenosine triphosphate and a significantly higher malondialdehyde
      concentration in the intestine and lung than did fasted rats. The ratio of
      adenosine triphosphate to adenosine diphosphate in the liver, an indicator of
      energy status, in fed rats was similar to that in a sham group, whereas fasted
      animals showed a significantly lower value. CONCLUSIONS: Preoperative nutrition
      in contrast to fasting may attenuate ischemia/reperfusion-induced injury and
      preserve organ function in the rat.

PMID- 15975496
TI  - Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid.
AB  - OBJECTIVE: We compared the effect of dietary phosphatidylcholine (PC) with that
      of triacylglycerol (TG), both with the same fatty acid profiles, on fatty
      infiltration in orotic acid (OA)-induced fatty liver of Sprague-Dawley rats.
      METHODS: Rats were fed an OA-supplemented diets containing TG (TG+OA group) or PC
      (20% of dietary lipid, PC+OA group) for 10 d. Rats fed the TG diet without OA
      supplementation served as the basal group. RESULTS: Administering OA
      significantly increased the weights and TG accumulation in livers of the TG+OA
      group compared with the basal group. These changes were attributed to significant
      increases in the activities of fatty acid synthase, malic enzyme, and glucose-6
      phosphate dehydrogenase, which are fatty acid synthetic enzymes, and
      phosphatidate phosphohydrolase, a rate-limiting enzyme of TG synthesis. However,
      the PC+OA group did not show TG accumulation and OA-induced increases of these
      enzyme activities. Further, a significant increase in the activity of carnitine
      palmitoyl transferase, a rate-limiting enzyme of fatty acid beta-oxidation, was
      found in the PC+OA group. CONCLUSIONS: Dietary PC appears to alleviate the OA
      induced hepatic steatosis and hepatomegaly, mainly through the attenuation of
      hepatic TG synthesis and enhancement of fatty acid beta-oxidation in Sprague
      Dawley rats.

PMID- 15975497
TI  - Diet-induced thermogenesis: variations among three isocaloric meal-replacement
      shakes.
AB  - OBJECTIVE: We determined whether significant differences exist in diet-induced
      thermogenesis among three low-calorie (1042 kJ, or 250 kcal), liquid meal
      replacement shakes of different macronutrient compositions: 1) 100% protein; 2)
      62% protein, 28% carbohydrate, and 10% fat (high protein/low carbohydrate); and
      3) 17% protein, 75% carbohydrate, and 8% fat (low protein/high carbohydrate).
      METHODS: Eight subjects (three men and five women) completed a randomized, double
      blind, crossover investigation involving three separate resting-and-reclining
      energy expenditure measurements taken before and after consumption of one of the
      shakes. Resting-and-reclining metabolic gas-exchange measurements were taken for
      30 min; subjects then drank a 20-oz shake, after which 3 h of additional resting
      and-reclining gas-exchange measurements were taken. RESULTS: A statistically
      significant difference in diet-induced thermogenesis (P<0.02) was found between
      the low protein/high carbohydrate shake (79+- 48 kJ) and the high protein/low
      carbohydrate shake (209+/-108 kJ). No significant differences in diet-induced
      thermogenesis were found in comparison with the 100% protein shake (136+/-81 kJ).
      No significant differences in the respiratory exchange ratio over 3 h (P=0.33)
      were found. CONCLUSIONS: Different types of low-calorie meal-replacement shakes
      do invoke significantly different thermogenic responses over a 3-h period.
      However, the 130-kJ (31-kcal) difference found in diet-induced thermogenesis
      represents only a small contribution to daily energy expenditure so that
      practical applications for weight-control management appear to be minimal.

PMID- 15975498
TI  - Scientific misconduct and unethical human experimentation: historic parallels and
      moral implications.
AB  - Although a great deal of human experimentation has been performed to elucidate
      information otherwise not obtainable, there are many recorded instances of
      unethical human experimentation. There is also a history of crimes that were
      committed and disguised as human experiments, best exemplified by the activities
      of some physicians in Nazi Germany from 1933 until 1945. As a direct result of
      these activities, a war-crimes trial after World War II resulted in the creation
      of the Nuremberg Code, to guide future human experimentation. Despite this,
      unethical experiments were conducted at major academic institutions in the United
      States in the years after World War II by otherwise normal physicians who did not
      feel that the Nuremberg Code applied to them personally. There are several
      possible explanations for such activities, but the desire for personal
      advancement is prominent among these. Episodes of scientific misconduct such as
      falsification of experimental data or of personal qualifications seem to be more
      commonly reported recently and have also been described in the popular press.
      This activity may also be motivated by desire for personal advancement, giving it
      a parallel to the conduct of unethical human experimentation. Education may be
      the best way to prevent these activities that may have similar motivating
      factors.

PMID- 15975499
TI  - In search of a reliable marker of zinc status-are we nearly there yet?

PMID- 15975500
TI  - To fast or not to fast before surgical stress.

PMID- 15975501
TI  - Still imperfect: overseeing clinical research.

PMID- 15975502
TI  - Advanced cell technology: embryonic-stem-cell-based regenerative medicine.

PMID- 15975503
TI  - Can scarred hearts be repaired? MG Biotherapeutics is testing cell therapy for
      heart repair.

PMID- 15975504
TI  - Nature's protection racket.
AB  - (2S)-4-amino-2-hydroxybutyrate (AHBA) is a side chain that is important for the
      antibiotic activities of aminoglycosides. The elucidation of the biosynthetic
      pathway to AHBA, by Spencer et al. in this issue of Chemistry & Biology [1],
      reveals several surprises and will facilitate biosynthetic engineering of new
      improved aminoglycoside antibiotics.

PMID- 15975505
TI  - Spatial control of protein synthesis.
AB  - Previously used to provide temporal control over cellular processes, "photocaged"
      small molecules can impart spatial control to in vitro models. In this issue of
      Chemistry & Biology, the Dore and Schuman labs report a system to block protein
      synthesis in a spatially confined manner with a photo-caged form of anisomycin
      [1].

PMID- 15975506
TI  - Off the shelf but not mass produced.
AB  - Using high-throughput screening, Jo et al. in this issue of Chemistry & Biology
      [1] have identified SEW2871 as a structurally unique sphingosine 1-phosphate(1)
      (S1P(1)) receptor agonist. SEW2871 binds to and activates the S1P(1) receptor and
      initiates a survival signaling pathway similar to that of S1P.

PMID- 15975507
TI  - Features of selective kinase inhibitors.
AB  - Small-molecule inhibitors of protein and lipid kinases have emerged as
      indispensable tools for studying signal transduction. Despite the widespread use
      of these reagents, there is little consensus about the biochemical criteria that
      define their potency and selectivity in cells. We discuss some of the features
      that determine the cellular activity of kinase inhibitors and propose a framework
      for interpreting inhibitor selectivity.

PMID- 15975508
TI  - Biologically active fluorescent farnesol analogs.
AB  - We describe ten polyene analogs of farnesol, typified by 3,7,11-trimethyl
      2,4,6,8,10-dodecapentenaldehyde oxime, which preserve the length, cross-section,
      and approximate hydrophobicity of farnesol. Four of the ten display strong quorum
      sensing activity in the human pathogen Candida albicans, with IC(50) values for
      inhibition of germ-tube formation as low as 10 microM. The polyenes display
      absorption maxima between 320 and 380 nm, with the extinction coefficients for
      the oximes approaching 100,000. All but two of the analogs are fluorescent, with
      excitation maxima varying over the range of 320-370 nm. Oxime anti-4, which can
      undergo fluorescence excitation at wavelengths beyond 400 nm, is demonstrated to
      be useful for confocal fluorescence microscopic imaging of fungal cells. The
      farnesol analogs are also expected to be useful for detection of farnesol binding
      proteins and in determination of farnesol pharmacokinetics.

PMID- 15975509
TI  - Dissecting RNA-interference pathway with small molecules.
AB  - RNA interference (RNAi) is a process whereby short-interfering RNAs (siRNA)
      silence gene expression in a sequence-specific manner. We have screened a
      chemical library of substituted dihydropteridinones and identified a nontoxic,
      cell permeable, and reversible inhibitor of the RNAi pathway in human cells.
      Biochemical and fluorescence resonance-energy transfer experiments demonstrated
      that one of the compounds, named ATPA-18, inhibited siRNA unwinding that occurred
      within 6 hr of siRNA transfection. Extracts prepared from ATPA-18-treated cells
      also exhibited a decrease in target RNA cleavage by activated RNA-induced
      silencing complex (RISC*). Interestingly, when activated RISC*, which harbors
      unwound antisense siRNA, was treated with ATPA-18 in vitro, target RNA cleavage
      was not affected, indicating that this compound inhibited siRNA unwinding or
      steps upstream of unwinding in the RNAi pathway. Our results also establish the
      timing of siRNA unwinding and show that siRNA helicase activity is required for
      RNAi. ATPA-18 analogs will therefore provide a new class of small molecules for
      studying RNAi mechanisms in a variety of model organisms and deciphering in vivo
      genetic functions through reverse genetics.

PMID- 15975511
TI  - Structure-based engineering of E. coli galactokinase as a first step toward in
      vivo glycorandomization.
AB  - In vitro glycorandomization is a rapid chemoenzymatic strategy to diversify
      complex natural product scaffolds. The glycorandomization sugar activation
      pathway is dependent upon the efficient construction of diverse sugar-1-phosphate
      libraries. In the context of the previously evolved GalK Y371H "gatekeeper"
      mutation, the active site M173L mutation described herein presents a kinase with
      remarkably broadened substrate range to include 28 diverse natural and unnatural
      sugars. Among these new substrates, 6-azido-6-deoxy-galactose and 6-azido-6-deoxy
      glucose present unique chemical probes to assess the utility of an E. coli
      Y371H/M173L-GalK-overproducing strain to generate unnatural sugar-1-phosphates in
      vivo. Remarkably, the in vivo conversion of both unnatural sugars rival that
      demonstrated in vitro. This notable in vivo success stands as the first step
      toward constructing short sugar-activation pathways in vivo and, ultimately, in
      vivo natural-product glycorandomization.

PMID- 15975510
TI  - Characterization of the sulfhydryl-sensitive site in the enzyme responsible for
      hydrolysis of 2-arachidonoyl-glycerol in rat cerebellar membranes.
AB  - We have previously reported that the endocannabinoid, 2-arachidonoyl-glycerol (2
      AG), is hydrolyzed in rat cerebellar membranes by monoglyceride lipase (MGL)-like
      enzymatic activity. The present study shows that, like MGL, 2-AG-degrading
      enzymatic activity is sensitive to inhibition by sulfhydryl-specific reagents.
      Inhibition studies of this enzymatic activity by N-ethylmaleimide analogs
      revealed that analogs with bulky hydrophobic N-substitution were more potent
      inhibitors than hydrophilic or less bulky agents. Interestingly, the substrate
      analog N-arachidonylmaleimide was found to be the most potent inhibitor. A
      comparison model of MGL was constructed to get a view on the cysteine residues
      located near the binding site. These findings support our previous conclusion
      that the 2-AG-degrading enzymatic activity in rat cerebellar membranes
      corresponds to MGL or MGL-like enzyme and should facilitate further efforts to
      develop potent and more selective MGL inhibitors.

PMID- 15975512
TI  - Biosynthesis of the unique amino acid side chain of butirosin: possible
      protective-group chemistry in an acyl carrier protein-mediated pathway.
AB  - Butirosins A and B are naturally occurring aminoglycoside antibiotics that have a
      (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. Semisynthetic addition of AHBA
      to clinically valuable aminoglycoside antibiotics has been shown both to improve
      their pharmacological properties and to prevent their deactivation by a number of
      aminoglycoside-modifying enzymes involved in bacterial resistance. We report here
      that the biosynthesis of AHBA from L-glutamate, encoded within a previously
      identified butirosin biosynthetic gene cluster, proceeds via intermediates
      tethered to a specific acyl carrier protein (ACP). Five components of the pathway
      have been purified and characterized, including the ACP (BtrI), an ATP-dependent
      ligase (BtrJ), a pyridoxal phosphate-dependent decarboxylase (BtrK), and a two
      component flavin-dependent monooxygenase system (BtrO and the previously
      unreported BtrV). The proposed biosynthetic pathway includes a gamma
      glutamylation of an ACP-derived gamma-aminobutyrate intermediate, possibly a rare
      example of protective group chemistry in biosynthesis.

PMID- 15975513
TI  - Synthetic alpha-mannosyl ceramide as a potent stimulant for an NKT cell
      repertoire bearing the invariant Valpha19-Jalpha26 TCR alpha chain.
AB  - A NKT cell repertoire is characterized by the expression of the Valpha19-Jalpha26
      invariant TCR alpha chain (Valpha19 NKT cell). This repertoire, as well as a well
      established Valpha14-Jalpha281 invariant TCR alpha(+) NKT cell subset (Valpha14
      NKT cell), has been suggested to have important roles in the regulation of the
      immune system and, thus, is a major therapeutic target. Here, we attempted to
      find specific antigens for Valpha19 NKT cells. Valpha19 as well as Valpha14 NKT
      cells exhibited reactivity to alpha-galactosyl ceramide (alpha-GalCer). Thus, a
      series of monoglycosyl ceramides with an axially oriented glycosidic linkage
      between the sugar and ceramide moiety were synthesized and their antigenicity to
      Valpha19 NKT cells was determined by measuring their immune responses in culture
      with glycolipids. Comprehensive examinations revealed substantial antigenic
      activity for Valpha19 NKT cells by alpha-mannosyl ceramide.

PMID- 15975514
TI  - Light-mediated inhibition of protein synthesis.
AB  - The regulation of protein synthesis is vital for a host of cell biological
      processes, but investigating roles for protein synthesis have been hindered by
      the inability to selectively interfere with it. To inhibit protein synthesis with
      spatial and temporal control, we have developed a photo-releasable anisomycin
      compound, N-([6-bromo-7-hydroxycoumarin-4-yl]methyloxycarbonyl)anisomycin (Bhc
      Aniso), that can be removed through exposure to UV light. The area of protein
      synthesis inhibition can be restricted to a small light-exposed region or,
      potentially, the volume of two-photon excitation if a pulsed IR laser is the
      light source. We have tested the compound's effectiveness with an in vitro
      protein-translation system, CHO cells, HEK293 cells, and neurons. The photo
      released anisomycin can inhibit protein synthesis in a spatially restricted
      manner, which will enable the specific inhibition of protein synthesis in subsets
      of cells with temporal and spatial precision.

PMID- 15975515
TI  - Oxidative DNA strand scission induced by peptides.
AB  - Cellular oxidative stress promotes chemical reactions causing damage to DNA,
      proteins, and membranes. Here, we describe experiments indicating that reactive
      oxygen species, in addition to degrading polypeptides and polynucleotides through
      direct reactions, can also promote damaging biomolecular cross reactivity by
      converting protein residues into peroxides that cleave the DNA backbone. The
      studies reported show that a variety of residues induce strand scission upon
      oxidation, and hydrogen abstraction occurring at the DNA backbone is responsible
      for the damage. The observation of peptide-promoted DNA damage suggests that
      crossreactions within protein/DNA complexes should be considered as a significant
      cause of the toxicity of reactive oxygen species.

PMID- 15975516
TI  - S1P1-selective in vivo-active agonists from high-throughput screening: off-the
      shelf chemical probes of receptor interactions, signaling, and fate.
AB  - The essential role of the sphingosine 1-phosphate (S1P) receptor S1P(1) in
      regulating lymphocyte trafficking was demonstrated with the S1P(1)-selective
      nanomolar agonist, SEW2871. Despite its lack of charged headgroup, the
      tetraaromatic compound SEW2871 binds and activates S1P(1) through a combination
      of hydrophobic and ion-dipole interactions. Both S1P and SEW2871 activated ERK,
      Akt, and Rac signaling pathways and induced S1P(1) internalization and recycling,
      unlike FTY720-phosphate, which induces receptor degradation. Agonism with
      receptor recycling is sufficient for alteration of lymphocyte trafficking by S1P
      and SEW2871. S1P(1) modeling and mutagenesis studies revealed that residues
      binding the S1P headgroup are required for kinase activation by both S1P and
      SEW2871. Therefore, SEW2871 recapitulates the action of S1P in all the signaling
      pathways examined and overlaps in interactions with key headgroup binding
      receptor residues, presumably replacing salt-bridge interactions with ion-dipole
      interactions.

PMID- 15975517
TI  - Forensic aspects of mass disasters: strategic considerations for DNA-based human
      identification.
AB  - Many mass disasters result in loss of lives. Law enforcement and/or public safety
      and health officials often have the responsibility for identifying the human
      remains found at the scene, so they can be returned to their families. The
      recovered human remains range from being relatively intact to highly degraded.
      DNA-based identity testing is a powerful tool for victim identification in that
      the data are not restricted to any particular one to one body landmark comparison
      and DNA profile comparisons can be used to associate separated remains or body
      parts. Even though DNA typing is straightforward, a disaster is a chaotic
      environment that can complicate effective identification of the remains. With
      some planning, or at least identification of the salient features to consider,
      stress can be reduced for those involved in the identification process. General
      guidelines are provided for developing an action plan for identification of human
      remains from a mass disaster by DNA analysis. These include: (1) sample
      collection, preservation, shipping and storage; (2) tracking and chain of custody
      issues; (3) laboratory facilities; (4) quality assurance and quality control
      practices; (5) parsing out work; (6) extraction and typing; (7) interpretation of
      results; (8) automation; (9) software for tracking and managing data; (10) the
      use of an advisory panel; (11) education and communication; and (12) privacy
      issues. In addition, key technologies that may facilitate the identification
      process are discussed, such as resin based DNA extraction, real-time PCR for
      quantitation of DNA, use of mini-STRs, SNP detection procedures, and software.
      Many of the features necessary for DNA typing of human remains from a mass
      disaster are the same as those for missing persons' cases. Therefore, developing
      a missing persons DNA identification program would also provide the basis for a
      mass disaster human remains DNA identification program.

PMID- 15975518
TI  - Oral erythroplakia--a review.
AB  - Oral erythroplakia (OE) is considered a rare potentially malignant lesion of the
      oral mucosa. Reports entirely devoted to OE are very few, and only two reviews
      none of which are of recent date have been published. Only the true, velvety, red
      homogeneous OE has been clearly defined while the terminology for mixed red and
      white lesions is complex, ill-defined and confusing. A recent case control study
      of OE from India reported a prevalence of 0.2%. A range of prevalences between
      0.02% and 0.83% from different geographical areas has been documented. OE is
      predominantly seen in the middle aged and elderly. One study from India showed a
      female:male ratio of 1:1.04. The soft palate, the floor of the mouth and the
      buccal mucosa is commonly affected. A specific type of OE occurs in chutta
      smokers in India. Lesions of OE are typically less than 1.5 cm in diameter. The
      etiology of OE reveals a strong association with tobacco consumption and the use
      of alcohol. Histopathologically, it has been documented that in OE of the
      homogenous type, 51% showed invasive carcinoma, 40% carcinoma in situ and 9% mild
      or moderate dysplasia. Recently, genomic aberrations with DNA aneuploidy has been
      demonstrated. p53 mutations with different degrees of dysplasia may play a role
      in some cases of OE. Transformation rates are considered to be the highest among
      all precancerous oral lesions and conditions. Surgical excision is the treatment
      of choice. Data on laser excision are not available. Recurrence rates seem to be
      high, reliable data are, however, missing. More studies on OE are strongly needed
      to evaluate a number of so far unanswered questions. The natural history of OE is
      unknown. Do OEs develop de novo or are they developing from oral leukoplakia
      through several intermediate stages of white/red lesions? The possible role of
      fungal infection (Candida micro-organisms) is not clear as is the possible role
      of HPV co-infection in the development of OE. More data on incidence and
      prevalence, biological behaviour and adequate treatment are urgently needed.

PMID- 15975519
TI  - Selection of topically applied non-steroidal anti-inflammatory drugs for oral
      cancer chemoprevention.
AB  - Topical delivery of non-steroidal anti-inflammatory drugs through the oral mucosa
      has been used for oral cancer chemoprevention. Local permeation of these agents
      has been one of the major concerns. Here we propose an approach to predict the
      permeability of topically applied agents for oral cancer chemoprevention. In
      theory, the total flux through the oral mucosa (Jmax) can be estimated by adding
      the transcellular flux (JTC) and the paracellular flux (JPC). To target the Cox-2
      enzyme in oral epithelial cells, it is desirable to maximize the theoretical
      activity index, the ratio of JTC and IC50 of a Cox-2 inhibitor (JTC/IC50-Cox-2).
      Among the 12 commonly used NSAIDs, celecoxib, nimesulide and ibuprofen had the
      highest values and may be the agents of choice to target Cox-2 in oral epithelial
      cells through topical application. Based on these calculations, a long-term
      chemopreventive experiment using celecoxib (3% or 6%) through topical application
      was performed in a DMBA induced hamster oral cancer model. Both 3% and 6% reduced
      the incidence of squamous cell carcinoma at the post-initiation stage.

PMID- 15975520
TI  - ICAM-5 (telencephalin) gene expression in head and neck squamous carcinoma
      tumorigenesis and perineural invasion!
AB  - ICAM-5 (telencephalin) is an intercellular adhesion molecule reported to be
      expressed only in the somatodendritic membrane of telencephalic neurons. We
      recently identified high ICAM-5 expression in a cDNA array study of head and neck
      neoplasms with a propensity for perineural invasion. To determine the association
      of this gene in tumorigenesis and perineural invasion, we analyzed the expression
      and functional status of ICAM-5 mRNA transcripts in 30 different human cancer
      cell lines and 25 head and neck squamous carcinoma specimens by reverse
      transcriptase polymerase chain reaction (cell lines and specimens) and in vitro
      functional assays (cell lines). ICAM-5 transcripts were detected in 28 (93%) of
      30 cell lines derived from primary head and neck, colon, thyroid, cervical,
      pancreatic, skin, and adenoid cystic carcinomas. In cell lines, small interfering
      RNA blocked ICAM-5 expression and inhibited cell proliferation. Treatment with
      the phosphatidylinositol 3'-kinase (PBK) inhibitor LY294002 resulted in ICAM-5
      down-regulation. In tissue specimens, none of the 25 histologically normal oral
      mucosal specimens had detectable ICAM-5 level, whereas 16 (64%) of the 25 matched
      primary squamous carcinomas showed expression. Carcinoma specimens high ICAM-5
      expression had a high incidence of perineural invasion. Our study indicates that
      ICAM-5 may play a role in tumorigenesis and perineural invasion, most likely
      through the P13K/Akt-signaling pathway.

PMID- 15975522
TI  - Nasopharyngeal cancer in the California Hmong, 1988-2000.
AB  - Although previous studies document elevated nasopharyngeal cancer incidence in
      the American Hmong, a descriptive analysis is lacking. The present case-series
      aims to identify important features of head and neck cancers in the California
      Hmong, specifically nasopharyngeal cancer. We assessed incident head and neck
      cancers identified by the California Cancer Registry from 1988-2000 for
      incidence, mortality and descriptive comparisons between the Hmong, non-Hispanic
      Whites (NHW) and Asian/Pacific Islanders (API). Nasopharyngeal cancer was the
      most frequent Hmong cancer (39 of 51 cases) with incidence 23 times greater than
      in NHW. Nasopharyngeal cancer mortality rates for Hmong, NHW and API were 10.4,
      0.2 and 1.7/100,000 respectively. Hmong were more likely to be diagnosed with
      remote tumors and less likely to receive treatment. A public health disparity
      clearly exists regarding nasopharyngeal cancer in the Hmong. Education on
      culturally appropriate healthcare and efforts to encourage diagnosis and
      treatment are necessary to reduce this disparity.

PMID- 15975521
TI  - A phase II study of docetaxel and cisplatin as first-line chemotherapy in
      patients with metastatic nasopharyngeal carcinoma.
AB  - To evaluate the efficacy and safety of docetaxel and cisplatin as first-line
      chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). Nineteen
      previously untreated metastatic NPC patients received one to six cycles of
      docetaxel and cisplatin. Fifteen patients received at least three cycles. The
      starting dose was 75 mg/m2 every three weeks for both drugs in 15 patients, and
      60 mg/m2 for both drugs in four patients. All patients were included in toxicity
      and survival analysis, and 16 patients were evaluable for response. Median follow
      up time was 11.6 months. Hematological toxicity was severe with Grade 4
      neutropenia in 78.9% patients and 51.3% cycles. Febrile neutropenia occurred in
      42% patients and 12.5% cycles, with two septic deaths in the population treated
      with 75 mg/m2. Patients treated with a dose subsequently reduced to 60 mg/m2 had
      a lower incidence of Grade 4 neutropenia and no incidence of neutropenic
      fever/sepsis. Overall response rate was 62.5%, with a 95% confidence interval of
      35-85%. Partial and complete response rates were 56.3% and 6.3%, respectively.
      Median time to progression was 5.6 months and median survival was 12.4 months.
      Three patients (15.6%) survived >2 years following chemotherapy. The combination
      of docetaxel and cisplatin is active in metastatic NPC. The dose of 60 mg/m2 for
      both drugs without colony-stimulating factor support should be further evaluated
      as a high incidence of febrile neutropenia was observed with 75 mg/m2 dose.

PMID- 15975523
TI  - Comparison of deltopectoralis flap and free radial forearm flap in reconstruction
      after oral cancer ablation.
AB  - Defects in the head and neck resulting from ablation of oral cancer frequently
      lead to disabling functional and cosmetic deformities. Rehabilitation of patients
      with oral cancer can be an emotionally and technically challenging endeavor.
      Selection of the donor tissue is clearly dependent upon the defect that is to be
      reconstructed. The donor tissue should be of sufficient bulk and pliability to
      facilitate reestablishing contour and function. Regional flap and free flap have
      been the mainstays of reconstruction for surgical defects after ablation of oral
      cancer. The records of 77 patients in whom 49 deltopectoral (DP) flaps and 28
      free radial forearm flaps (FRFF) were used were analyzed. The success rate of the
      DP flap was 89.8% and of the FRFF was 96.4%. The minor complication rate at the
      transplant site (fistula, dehiscence, hematoma) for the DP flaps was 22.4% and
      for the FRFFs was 14.3%. Overall complication rate at the transplant site for DP
      flaps was 32.7% and for the FRFFs was 17.9%. The incidence of partial loss of the
      donor-site skin graft was 4.1% for the DP flaps and 10.7% for the FRFFs. Overall
      complication rate at the donor site for DP flaps was 10.2% and for the FRFFs was
      39.3%. DP flaps had better aesthetic and functional results at the donor site,
      than FRFFs. However, the DP flap is a staged procedure and results in prolonged
      hospitalization. In contrast to FRFF, performing a DP flap avoids the difficult
      technique of microanastomosis, and therefore reduces the donor-site complication
      rate and the operation time. Therefore, free flaps can not be routinely
      substituted for regional flaps, but they represent better reconstructive
      alternatives for specific and selected patients.

PMID- 15975524
TI  - Differential expression of the keratin-4, -13, -14, -17 and transglutaminase 3
      genes during the development of oral squamous cell carcinoma from leukoplakia.
AB  - To identify differentially expressed genes during the development of oral
      malignancy, differential display, northern blotting, reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemical analyses were
      undertaken using oral squamous cell carcinoma (OSCC) and leukoplakia tissues.
      Significantly higher levels of keratin (Ker)-14 and -17 mRNAs, combined with
      lower levels of Ker-4, Ker-13 and transglutaminase 3 (TG-3) transcripts, were
      observed in OSCC and severely dysplastic tissues, whereas this expression profile
      was reversed in hyperplasia and in mild to moderate dysplasia. The expression of
      Ker-4 and Ker-13 was elevated in density-arrested OSCC cell lines (Ca9-22, HSC-2,
      -3 and -4) but the expression of Ker-17 mRNA was elevated in these cells,
      regardless of the growth conditions. In addition, Ker-4 and Ker-13 proteins were
      predominantly expressed in moderate dysplasia and hyperplasia, whereas Ker-17 was
      markedly expressed in OSCC tissues. The expression patterns of these genes could
      therefore be an important determinant of the manifestation of oral malignancy.

PMID- 15975525
TI  - Promotor hypermethylation of p14ARF is a key alteration for progression of oral
      squamous cell carcinoma.
AB  - We investigated the promotor hypermethylation status of multiple genes in 49 oral
      squamous cell carcinomas (OSCC), using the methylation-specific PCR (MSP) assay.
      The genes examined included p16INK4a, p14ARF, RB1, p21Waf1, p27Kip1, PTEN, p73,
      0(6)-MGMT, and GST-P. Detailed clinicopathological data, such as patient age,
      sex, tobacco use, alcohol consumption, lesion site, degree of tumor
      differentiation, tumor size, presence of lymph node metastasis, and clinical
      stage, were collected for all 49 samples. Overall, gene methylation was detected
      in 46.9% (23/49) of samples and was closely correlated with tobacco use or/and
      alcohol consumption. Of the genes investigated, p16INK4a, p14ARF, 0(6)-MGMT, RB1,
      PTEN, and p27Kip1 were found to be methylated in 34.7%, 20.4%, 12.2%, 10.2%,
      6.1%, and 4.1% of these 49 tumors, respectively, but methylation of p21Waf1, p73,
      and GST-P was not detected at all. Methylation frequencies were much higher for
      each gene when computed among informative cases only. Concurrent promotor
      hypermethylation of p16INK4a and p14ARF correlated significantly with tumor size,
      lymph node metastasis, and stage III/IV advanced OSCC; p14ARF hypermethylation,
      in particular, was significantly associated with both lymph node metastasis and
      late clinical stage. Our results suggest that DNA methylation of multiple genes,
      especially hypermethylation of the p14ARF promoter, is common in OSCC and is
      associated with the use of tobacco and/or alcohol consumption. For this type of
      cancer, the data further implicates gene methylation as playing an important role
      in tumor progression.

PMID- 15975526
TI  - Glycerol enhances radiosensitivity in a human oral squamous cell carcinoma cell
      line (Ca9-22) bearing a mutant p53 gene via Bax-mediated induction of apoptosis.
AB  - Radiotherapy for oral squamous cell carcinomas is limited in its efficacy and in
      its ability to improve the survival rate in patients at an advanced stage. A
      protocol is described here which may elevate the therapeutic efficacy of
      radiation for these cells. The addition of glycerol to the culture medium prior
      to irradiation of an oral squamous cell carcinoma cell line (Ca9-22) bearing a
      mutant p53 (mp53) gene was found to increase the radiosensitivity of these cells.
      A colony formation assay was used to evaluate the effect of glycerol on the
      radiation sensitivity of Ca9-22 cells. Apoptosis was analyzed using Hoechst 33342
      staining, Western blotting, and a DNA ladder formation assay. Glycerol, when
      present in the culture medium, enhanced the radiation sensitivity and extent of
      apoptosis following X-irradiation in the Ca9-22 cells, although neither X-rays or
      glycerol alone increased the extent of apoptosis. Bax protein was accumulated
      after treatment with X-rays plus glycerol, but not after exposure to X-rays or
      glycerol alone. A gel mobility-shift assay showed that glycerol restored the DNA
      binding activity of mp53 for a p53-consensus sequence to levels similar to that
      of wild-type p53. These findings suggest that pre-treatment with glycerol may
      enhance the effectiveness of radiotherapy against oral squamous cell carcinomas
      bearing an mp53 gene mutation.

PMID- 15975527
TI  - Cancer: undifferentiation or specialization?

PMID- 15975528
TI  - A procedure for culturing astrocytes from white matter and the application of the
      siRNA technique for silencing the expression of their specific marker, S100A4.
AB  - White matter astrocytes have physiological functions which are distinct from
      those of astrocytes in gray matter. White matter becomes highly non-permissive to
      neurite growth after injury, but the role of white matter astrocytes in this
      process is incompletely understood. Current protocols for making primary
      astroglial cultures are inadequate for exploring the specific properties of white
      matter astrocytes in vitro. We describe a procedure for obtaining cultures of
      white matter astrocytes from the rodent corpus callosum. In this procedure, we
      take advantage of our previous finding that white, but not gray matter astrocytes
      express the calcium-binding protein S100A4. S100A4 expressing astrocytes are
      abundant in the corpus callosum, and we show that cultures, highly enriched in
      S100A4 expressing white matter astrocytes, can be reproducibly generated from
      this area. Key factors for successful cultures are (i) meticulous dissection of
      the corpus callosum from 4-day-old rats, and (ii) Percoll density gradient
      centrifugation to purify astrocytes. As a means of exploring the possible role of
      S100A4 in white matter astrocytes, we describe the use of the siRNA technique to
      eliminate the expression of S100A4 in our in vitro system.

PMID- 15975529
TI  - In vivo preparation and identification of mitral cells in the main olfactory bulb
      of the mouse.
AB  - The mouse main olfactory bulb (MOB) is commonly used as a mammalian model to
      study olfactory processing. The genetic techniques available with the mouse make
      its MOB a powerful model for analysis of neuronal circuitry. The mouse has been
      used as a mammalian model for all types of MOB neurons, but especially to study
      the activity of mitral cells. However, mouse mitral cell activity is most
      commonly studied in vitro. Therefore, we aimed to develop a protocol to record
      the activity of antidromically identified mitral cells in mouse in vivo.
      Currently, such a protocol does not exist. Using extracellular techniques, we
      report a protocol that is able to record neurons from all mouse MOB layers.
      Specifically, mitral cell single-units were identified by antidromic activation
      from the posterior piriform cortex, and their spontaneous activity was recorded
      for more than 30 min. This protocol is stable enough to record from single-units
      while buprenorphine was applied both topically to the surface of the MOB and
      injected systemically.

PMID- 15975530
TI  - Vascular reactivity of mesenteric arteries and veins to endothelin-1 in a murine
      model of high blood pressure.
AB  - We characterized vascular reactivity to endothelin-1 (ET-1) in mesenteric vessels
      from DOCA-salt hypertensive and SHAM control mice and assessed the effect that
      endothelial-derived vasodilators have on ET-1-induced vasoconstriction. Changes
      in the diameter of unpressurized small mesenteric arteries and veins (100- to 300
      microm outside diameter) were measured in vitro using computer-assisted video
      microscopy. Veins were more sensitive than arteries to the contractile effects of
      ET-1. There was a decrease in arterial maximal responses (E(max)) compared to
      veins, this effect was larger in DOCA-salt arteries. The selective ET(B) receptor
      agonist, sarafotoxin 6c (S6c), contracted DOCA-salt and SHAM veins but did not
      contract arteries. The ET(B) receptor antagonist, BQ-788 (100 nM), but not the
      ET(A) receptor antagonist, BQ-610 (100 nM), blocked S6c responses. BQ-610
      partially inhibited responses to ET-1 in mesenteric veins from DOCA-salt and SHAM
      mice while BQ-788 did not affect responses to ET-1. Co-administration of both
      antagonists inhibited responses to ET-1 to a greater extent than BQ-610 alone
      suggesting a possible functional interaction between ET(A) and ET(B) receptors.
      Responses to ET-1 in mesenteric arteries were completely inhibited by BQ-610
      while BQ-788 did not affect arterial responses. Nitric oxide synthase inhibition
      potentiated ET-1 responses in veins from SHAM but not DOCA-salt mice. There was a
      prominent role for ET-mediated nitric oxide release in DOCA-salt but not SHAM
      arteries. In summary, these studies showed a differential regulation of ET-1
      contractile mechanisms between murine mesenteric arteries and veins.

PMID- 15975531
TI  - Cardiovascular effects of trans-dehydrocrotonin, a diterpene from Croton cajucara
      in rats.
AB  - Previous studies have established the gastroprotective, hypoglycemic, and
      hypolipidemic effects of trans-dehydrocrotonin (t-DCTN), a major diterpene
      isolated from the Amazon medicinal plant Croton cajucara. This study aims to
      examine the potential effects of t-DCTN on hemodynamic parameters that include
      resting arterial blood pressure and heart rate in vivo, and on left atrial force,
      spontaneous beating atria, and aortic rings of rats in vitro. Intravenous bolus
      injections of t-DCTN (5, 10, or 15 mg/kg) to urethane anesthetized normotensive
      rats reduced the mean arterial pressure and heart rate in a dose-dependent
      manner. The hypotensive effect of t-DCTN (10 mg/kg) appears not mediated through
      effects on the muscarinic cholinergic receptor, beta-adrenoceptor, or ganglionic
      blockade, for it was not affected by atropine, propranolol, or hexamethonium but
      was abolished by N(w)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide
      synthase inhibitor. The diterpene t-DCTN showed no significant influence on
      inotropism. In isolated rat aortic rings with intact or denuded endothelium, t
      DCTN relaxed the tonic contraction induced by phenylephrine (1 microM). Its
      vasorelaxant effect seen at smaller concentrations in endothelium intact
      preparations was, however, abolished in endothelium denuded or in l-NAME treated
      tissues. These data indicate the hypotensive and bradycardia effects of t-DCTN,
      possibly related in part to the release of nitric oxide and in part to direct
      effects on vascular smooth muscle, and cardiac pacemaker activity.

PMID- 15975532
TI  - A novel and selective endothelin ET(A) receptor antagonist YM598 prevents the
      development of chronic hypoxia-induced pulmonary hypertension in rats.
AB  - The preventive effects of the novel and selective endothelin ET(A) receptor
      antagonist YM598 on the development of pulmonary hypertension (PH) were
      investigated in chronic hypoxia-induced PH rats. Oral administration of YM598 at
      a dose of 1 mg/kg was started on the first day of chronic hypoxia exposure for 2
      and 3 weeks to investigate the effects of this compound on hemodynamic and
      arterial blood gas variables, respectively. Cardiopulmonary organ weights were
      measured at the end of the 2-week administration period. Chronic hypoxia for 2
      weeks induced a marked increase in pulmonary arterial pressure, right ventricular
      hypertrophy, and pulmonary and systemic congestion, and a decrease in right
      cardiac diastolic function. Repeated oral administration of YM598 significantly
      suppressed the increase in pulmonary arterial pressure, right ventricular
      hypertrophy, and pulmonary and systemic congestion. YM598 also improved the
      hypoxemia which was induced by 3 weeks of exposure to hypoxia. These results
      suggest that repeated oral administration of YM598 to rats with chronic hypoxia
      effectively prevented the development of PH. Oral administration of YM598 also
      improved hypoxemia in this model. These data strongly suggest that YM598 will be
      clinically useful in the treatment of patients with either primary or secondary
      pulmonary hypertension.

PMID- 15975533
TI  - Does this patient have oesophageal motility abnormality or pathological acid
      reflux?
AB  - BACKGROUND AND AIMS: The diagnostic values of particular symptoms centred on
      oesophagus, among patients with suspected oesophageal motility abnormality or
      pathological acid exposure, are not yet fully understood. The aim of this study
      was to determine the predictive accuracy of these symptoms in diagnosis of
      oesophageal motility disorder or pathological acid exposure. PATIENTS AND
      METHODS.: A total of 462 patients who had undergone conventional oesophageal
      manometry and ambulatory 24-h pH monitoring to investigate a clinical suspicion
      of oesophageal motility disorder and pathological acid exposure were enrolled in
      this study. According to their principal complaints, the patients were divided
      into the dysphagia category, the non-cardiac chest pain category, the
      gastrooesophageal reflux disease-related symptom category and the
      extraoesophageal symptom category. RESULTS: Two hundred and two (44%) out of 462
      patients yielded abnormal findings on manometry and/or pH monitoring. Dysphagia
      was associated with a likelihood ratio (LR) of 2.11 [95% confidence interval
      (CI), 1.02-4.00)] in patients exhibiting a combination of oesophageal motility
      abnormality and pathological acid exposure. During oesophageal manometry, the
      dysphagia substantially increased the likelihood of classic achalasia (LR, 6.24;
      95% CI, 3.32-8.78) and diffuse oesophageal spasm (LR, 3.58; 95% CI, 1.03-7.12).
      When the patients with dysphagia were divided into two groups according to the
      severity of their symptoms, classic achalasia was significantly frequent in
      patients with severe dysphagia (P = 0.016). On the other hand, non-cardiac chest
      pain was the clinical factor that reduced the likelihood of classic achalasia
      (LR, 0.22; 95% CI, 0.04-0.93). The distribution of pathological acid exposure was
      significantly frequent between the groups of patients with and without
      gastrooesophageal reflux disease-related symptom (P = 0.011). CONCLUSION: A small
      number of oesophageal symptoms are helpful in predicting the likelihood of
      abnormal findings on oesophageal tests among patients with a clinical suspicion
      of oesophageal motility disorder and pathological acid exposure. The most useful
      finding is a severe dysphagia, which is likely to have classic achalasia.

PMID- 15975534
TI  - Helicobacter pylori infection influences symptomatic response to anti-secretory
      therapy in patients with GORD--crossover comparative study with famotidine and
      low-dose lansoprazole.
AB  - BACKGROUND AND AIM: Helicobacter pylori infection was reported to affect gastric
      acid secretion. We investigated the heartburn symptoms of patients with gastro
      oesophageal reflux disease during sequential treatment with 40 mg of famotidine
      or 15 mg of lansoprazole to clarify whether H. pylori infection influences
      symptomatic response to anti-secretory therapy. SUBJECTS AND METHODS: The
      subjects were 33 gastro-oesophageal reflux disease patients, who had already been
      treated with a full dose of H2 receptor antagonist. First, famotidine at 20 mg
      b.i.d. was administered to the patients for 8 weeks. Second, famotidine was
      replaced with 15 mg of lansoprazole once in the morning for 8 weeks. Finally, 20
      mg of famotidine was administered b.i.d. for 8 weeks instead of lansoprazole.
      Gastro-oesophageal reflux disease symptoms were assessed using an original visual
      analogue scale. RESULTS: The sequential symptomatic responses to famotidine and
      lansoprazole administration indicated that gastro-oesophageal reflux disease
      symptoms of patients during low-dose lansoprazole treatment were significantly
      less than those during famotidine treatment. Remission of symptoms was obtained
      significantly more often by famotidine therapy in patients with H. pylori
      infection than in patients without H. pylori infection. CONCLUSION: Low-dose
      lansoprazole is more effective than full-dose famotidine for the control of
      symptoms in patients with gastro-oesophageal reflux disease, and H. pylori
      infection influences the symptomatic response to H2 receptor antagonists.

PMID- 15975535
TI  - Photodynamic therapy for early oesophageal cancer.
AB  - BACKGROUND: Photodynamic therapy is an endoscopic treatment of early cancers
      based on the photosensitisation of neoplasms following the administration of a
      photosensitiser prior to laser light-induced tissue destruction. AIM: To assess
      the results of photodynamic therapy using Photofrin(Axcan Pharma Inc., Quebec,
      Canada) in patients with an early oesophageal cancer. PATIENTS: Twenty-four
      patients with early oesophageal cancer presenting as a not well-demarcated
      irregular dyschromic area of mucosa and unsuitable for any other treatment
      underwent photodynamic therapy. RESULTS.: Seventy-five per cent were successfully
      treated; three of them recurred and two died from head and neck cancer. To date,
      54% of patients are alive without recurrence; the average follow-up is 21 months.
      There were one oesophageal lethal perforation and six stenosis. Results of
      photodynamic therapy were limited in this series by three failures, three
      recurrences and three deaths from previous head and neck cancers. CONCLUSION:
      This study provides some promising data for photodynamic therapy of oesophageal
      carcinomas in selected patients. It also emphasises the need for a best delivery
      device of laser light.

PMID- 15975536
TI  - Quadruple therapy with lactoferrin for Helicobacter pylori eradication: a
      randomised, multicentre study.
AB  - BACKGROUND: Helicobacter pylori eradication rate with standard triple therapies
      is decreasing. Recently, lactoferrin administration has been shown to
      significantly increase the cure rate of 7-day rabeprazole, clarithromycin and
      tinidazole triple therapy. We assessed whether lactoferrin also increases the
      eradication rate of 7-day esomeprazole, clarithromycin and amoxycillin triple
      therapy as first-line treatment. METHODS: Overall, 133 consecutive patients with
      non-ulcer dyspepsia and H. pylori infection were randomised to receive either a
      standard 7-day triple therapy with esomeprazole 20mg b.i.d., clarithromycin 500
      mg b.i.d. and amoxycillin 1g b.i.d. (68 patients) or a quadruple therapy
      comprising of the same regimen plus lactoferrin 200mg b.i.d. (65 patients). H.
      pylori at entry was assessed by endoscopy, while bacterial eradication was
      checked by (13)C urea breath test 4-6 weeks after treatment. RESULTS: H. pylori
      eradication following standard triple therapy was achieved in 53/68 (77.9%; 95%
      CI = 68-88) and in 53/66 (80.3%; 95% CI = 71-89) patients at ITT and PP analyses,
      respectively. Following the quadruple regimen, the infection was cured in 50/65
      (76.9%; 95% CI = 67-87) and 50/64 (78.1%; 95% CI = 68-88) patients at ITT and PP
      analyses, respectively. No statistically significant difference emerged between
      the two therapeutic regimens, both at ITT (p = 0.9) and PP analyses (p = 0.9).
      Side effects were complained by seven (10.3%) patients and six (9.2%) patients
      following the triple and quadruple regimens, respectively (p = 0.9), with only
      one patient in the quadruple group interrupting the treatment due to side
      effects. CONCLUSIONS: Quadruple therapy with lactoferrin did not significantly
      increase the H. pylori cure rate of standard 7-day clarithromycin-amoxycillin
      based triple therapy in non-ulcer dyspepsia patients.

PMID- 15975537
TI  - Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti
      Helicobacterpylori antibodies in the management of dyspeptic patients in primary
      care.
AB  - BACKGROUND: Several tests have been proposed for evaluating dyspeptic symptoms
      and their relationship to the underlying gastric disease. Serum pepsinogens and
      gastrin-17 are known to be useful biomarkers for the detection of gastric
      pathologies. AIM: To evaluate the capability of screening dyspeptic patients in
      the primary care by analyses of serum pepsinogens I (sPGI) and II (sPGII),
      gastrin-17 (sG-17) and the IgG anti-Helicobacter pylori antibodies (IgG-Hp).
      PATIENTS AND METHODS: Three hundred and sixty-two consecutive patients with
      dyspeptic symptoms (208 females, mean age 50.6 +/- 16 years, range 18-88 years)
      referred by general practitioners for upper gastrointestinal endoscopy were
      enrolled. A blood sample was taken from each subject for IgG-Hp, sPGI, sPGII and
      sG-17 analyses. RESULTS: Two hundred and eighty-seven patients had a complete
      screening; of these, 132 resulted positive for Hp infection. Patients with
      atrophic chronic gastritis showed significantly lower serum pepsinogen I levels
      and sPGI/sPGII ratio than patients with non-atrophic chronic gastritis. Moreover,
      by calculating the values of sPGI by sG-17 and sG-17 by sPGII/sPGI, subjects with
      atrophic chronic gastritis could be distinguished from those with non-atrophic
      chronic gastritis and from those with normal mucosa, respectively. sG-17 levels
      were found to be a useful biomarker for the detection of antral atrophic
      gastritis, while the combination of sPGI, the sPGI/sPGII ratio and sG-17 was
      found effective in identifying corpus atrophy. CONCLUSION: A panel composed of
      PGI, PGII, G-17 and IgG-Hp could be used as a first approach in the 'test and
      scope' and/or 'test and treat' strategy in the primary care management of
      dyspeptic patients.

PMID- 15975538
TI  - Serum bile acids, programmed cell death and cell proliferation in the mucosa of
      patients with colorectal adenomas.
AB  - BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with
      cell proliferation may favour colorectal tumourigenesis according to 'in vitro'
      studies, but information is lacking on the relationships occurring 'in vivo' in
      humans. AIMS: To evaluate whether serum deoxycholic acid is associated with
      programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10
      patients with colorectal adenomas, we measured fasting serum levels of bile
      acids; and, in normal colonic mucosa, programmed cell death by the TUNEL
      technique and cell proliferation by immunohistochemical staining with anti-Ki67.
      Total and compartmental indices for both activities were calculated. RESULTS:
      Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/-
      0.54 95% CI), showed a significant positive correlation with the total and basal
      compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no
      correlation with either total PCD Index, or bile acids. Within the median
      compartment of the crypt, cell proliferation was negatively associated with all
      unconjugated bile acids. CONCLUSIONS: The positive association between
      deoxycholic acid and programmed cell death in the basal compartment of the crypt,
      and the negative association of cell proliferation and unconjugated bile acids in
      the median compartment, do not seem to support the co-carcinogenic effect of
      deoxycholic acid.

PMID- 15975539
TI  - Selective granulocyte and monocyte apheresis as a new adjunct to enhance the
      efficacy of interferon-alpha + ribavirin in patients with high plasma hepatitis C
      virus.
AB  - BACKGROUND AND AIM: Selective granulocyte and monocyte/macrophage adsorptive
      apheresis is to increase the turnover of infected leucocytes and has increased
      CD4+ T cells, which are necessary for actions of interferon-alpha on hepatitis C
      virus. Therefore, granulocyte and monocyte apheresis was to enhance the efficacy
      of interferon + ribavirin. METHODS: Fifteen patients, 12 had interferon resistant
      hepatitis C virus and 3 were interferon naive. Hepatitis C virus genotype was 1b
      in 11 and 2a in 4. The mean plasma HCV-RNA was 728.3 kU/mL and alanine
      aminotransferase was 107.5 U/L. Granulocyte and monocyte apheresis was with the
      Adacolumn, which contains carriers that adsorb granulocytes and
      monocytes/macrophages. After five consecutive granulocyte and monocyte apheresis
      sessions over 5 days, interferon daily 6 million units for 4 weeks, then three
      times/week for 20 weeks+ribavirin (600-800 mg per patient per day) were given and
      followed for another 24 weeks. RESULTS: During granulocyte and monocyte
      apheresis, plasma HCV-RNA transiently fell by up to 55%. Similarly, incubation of
      blood with the Adacolumn carriers caused a significant fall in HCV-RNA. Four
      patients were unavailable for efficacy evaluation. In the other 11, alanine
      aminotransferase normalised and at 11 weeks, plasma HCV-RNA was negative; six of
      these (55%) maintained their remission during the follow up. CONCLUSION:
      Granulocyte and monocyte apheresis appears to deplete extra-hepatic hepatitis C
      virus reservoirs and generate active complement opsonins, which contribute to
      hepatitis C virus killing. Additional mechanism(s) are also likely and need to be
      elucidated in future studies with larger cohort of patients.

PMID- 15975540
TI  - Serum selenium concentrations in chronic pancreatitis and controls.
AB  - BACKGROUND: In the light of the recent hypothesis that one cause of pancreatic
      damage may be related to the toxic action of oxygen free radicals [Braganza JM.
      The pathogenesis of pancreatitis. Manchester: Manchester University Press; 1991;
      Braganza JM. A framework for the aetiogenesis of chronic pancreatitis. Digestion
      1998;59(Suppl. 4):1-12], we were prompted to assess the role of selenium in
      pancreatic disease. OBJECTIVE: The objective of the study was to establish
      whether or not there is any correlation between selenium levels and the degree of
      impairment of exocrine pancreatic function in patients suffering from chronic
      pancreatitis. PATIENTS: Two groups of subjects were recruited, the first
      consisting of 38 patients with clinically quiescent chronic pancreatitis of
      alcoholic origin and the second of 48 control subjects selected from among
      healthy volunteers attending our Transfusion Centre. METHODS: Body mass index,
      smoking and drinking habits were evaluated and selenium serum levels were assayed
      in all subjects. The patients with pancreatic disease were subdivided into three
      groups on the basis of lipase output assayed with a duodenal probe. RESULTS.:
      Selenium serum levels in the chronic pancreatitis group as a whole were found to
      be significantly lower than in the control group, but when they were analysed in
      the three distinct subgroups, a significant difference was found against control
      group only in the groups with severe and moderate exocrine pancreatic
      insufficiency. CONCLUSIONS: The mean serum selenium levels were lower in chronic
      pancreatitis patients than control.

PMID- 15975541
TI  - Is it possible to reduce endoscopy workload using age, alarm symptoms and H.
      pylori as predictors of peptic ulcer and oesophagogastric cancers?
AB  - OBJECTIVES: We examined referrals to oesophagogastroduodenoscopy and the impact
      of demographic and clinical variables to predict major findings (peptic ulcer,
      cancer) on oesophagogastroduodenoscopy. METHODS: We collected data on 3669
      consecutive patients referred for oesophagogastroduodenoscopy. RESULTS: Dyspeptic
      and reflux symptoms constituted 80% of oesophagogastroduodenoscopy referrals. A
      major finding was observed in 419 patients (11.4%). The mean age of cancer
      patients was 72.7 years (95% confidence interval (CI) 70.0-76.5 years) and that
      of peptic ulcer patients 62.0 years (95% CI 60.5-63.5 years). Independent risk
      factors for a major finding were age >50 years (odds ratio (OR) 1.62, 95% CI 1.24
      2.10), male sex (OR 1.38, 95% CI 1.11-1.72), ulcer-type pain (OR 2.33, 95% CI
      1.80-3.02), weight loss (OR 1.70, 95% CI 1.14-2.53), anaemia (OR 1.82, 95% CI
      1.38-2.40), bleeding symptoms (OR 3.27, 95% CI 2.26-4.75) and Helicobacter pylori
      (OR 2.49, 95% CI 2.00-3.11), whereas reflux symptoms were protective (OR 0.73,
      95% CI 0.53-1.00). The area under receiver operating characteristic curve of age
      over 50 years with alarm symptoms to predict major finding was 0.68 (95% CI 0.65
      0.71), which positive H. pylori status increased to 0.71 (95% CI 0.69-0.74). Of
      the major findings, 87.2% were detected in patients with risk factors. Major
      findings were detected in 15.1% patients with and 8.1% (p < 0.001) without alarm
      symptoms. CONCLUSIONS: Dyspeptic and reflux symptoms constitute the majority of
      oesophagogastroduodenoscopy workload. Discriminative power of alarm symptoms even
      with positive H. pylori status to detect peptic ulcer or cancer was low. Because
      of their low cancer risk, reflux and dyspeptic patients younger than 50 years can
      be treated without oesophagogastroduodenoscopy.

PMID- 15975542
TI  - Cystic lymphangioma associated with enteric duplication as a cause of recurrent
      vomiting.
AB  - We describe a case report of a 6-year-old boy with a 4-year history of recurrent
      vomiting with a cyclical vomiting pattern. Although initially labelled with and
      treated for Cyclical Vomiting Syndrome the cause was subsequently found to be an
      enteric duplication associated with cystic lymphangioma, an association not
      previously described.

PMID- 15975543
TI  - Primary signet-ring cell carcinoma mimicking segmental Crohn's colitis.
AB  - Primary signet-ring cell carcinoma of the colon is a rare entity with a dismal
      prognosis, mainly due to a delay in diagnosis. Here, we present a case of a 30
      year-old Filipino woman who presented with symptoms mimicking inflammatory bowel
      disease. A barium enema and colonoscopy demonstrated a stricture in the
      rectosigmoid region. A biopsy revealed granulomatous changes indicative of
      inflammatory bowel disease. Despite initial improvement of her symptoms on total
      parenteral nutrition and steroids, the patient relapsed several weeks later with
      recurrent left lower quadrant pain. A subsequent biopsy revealed poorly
      differentiated signet-ring cell carcinoma of the colon. She was treated
      surgically with a left hemi-colectomy and primary repair. A high degree of
      suspicion is necessary to correctly diagnose these, often young, patients with
      primary signet-ring cell carcinoma early and have a positive impact on survival.
      The literature on primary signet-ring cell carcinoma is reviewed.

PMID- 15975544
TI  - Two-year results of a randomised double-blinded trial evaluating silymarin for
      chronic hepatitis C.

PMID- 15975545
TI  - Modelling of the electron transfer reactions in Photosystem I by electron
      tunnelling theory: the phylloquinones bound to the PsaA and the PsaB reaction
      centre subunits of PS I are almost isoenergetic to the iron-sulfur cluster F(X).
AB  - Photosystem I is a large macromolecular complex located in the thylakoid
      membranes of chloroplasts and in cyanobacteria that catalyses the light driven
      reduction of ferredoxin and oxidation of plastocyanin. Due to the very negative
      redox potential of the primary electron transfer cofactors accepting electrons,
      direct estimation by redox titration of the energetics of the system is hampered.
      However, the rates of electron transfer reactions are related to the
      thermodynamic properties of the system. Hence, several spectroscopic and
      biochemical techniques have been employed, in combination with the classical
      Marcus theory for electron transfer tunnelling, in order to access these
      parameters. Nevertheless, the values which have been presented are very variable.
      In particular, for the case of the tightly bound phylloquinone molecule A(1), the
      values of the redox potentials reported in the literature vary over a range of
      about 350 mV. Previous models of Photosystem I have assumed a unidirectional
      electron transfer model. In the present study, experimental evidence obtained by
      means of time resolved absorption, photovoltage, and electron paramagnetic
      resonance measurements are reviewed and analysed in terms of a bi-directional
      kinetic model for electron transfer reactions. This model takes into
      consideration the thermodynamic equilibrium between the iron-sulfur centre F(X)
      and the phylloquinone bound to either the PsaA (A(1A)) or the PsaB (A(1B))
      subunit of the reaction centre and the equilibrium between the iron-sulfur
      centres F(A) and F(B). The experimentally determined decay lifetimes in the range
      of sub-picosecond to the microsecond time domains can be satisfactorily
      simulated, taking into consideration the edge-to-edge distances between redox
      cofactors and driving forces reported in the literature. The only exception to
      this general behaviour is the case of phylloquinone (A(1)) reoxidation. In order
      to describe the reported rates of the biphasic decay, of about 20 and 200 ns,
      associated with this electron transfer step, the redox potentials of the quinones
      are estimated to be almost isoenergetic with that of the iron sulfur centre F(X).
      A driving force in the range of 5 to 15 meV is estimated for these reactions,
      being slightly exergonic in the case of the A(1B) quinone and slightly
      endergonic, in the case of the A(1A) quinone. The simulation presented in this
      analysis not only describes the kinetic data obtained for the wild type samples
      at room temperature and is consistent with estimates of activation energy by the
      analysis of temperature dependence, but can also explain the effect of the
      mutations around the PsaB quinone binding pocket. A model of the overall
      energetics of the system is derived, which suggests that the only substantially
      irreversible electron transfer reactions are the reoxidation of A(0) on both
      electron transfer branches and the reduction of F(A) by F(X).

PMID- 15975546
TI  - Inhibition of plasma membrane Ca(2+)-ATPase by CrATP. LaATP but not CrATP
      stabilizes the Ca(2+)-occluded state.
AB  - The bidentate complex of ATP with Cr(3+), CrATP, is a nucleotide analog that is
      known to inhibit the sarcoplasmic reticulum Ca(2+)-ATPase and the Na(+),K(+)
      ATPase, so that these enzymes accumulate in a conformation with the transported
      ion (Ca(2+) and Na(+), respectively) occluded from the medium. Here, it is shown
      that CrATP is also an effective and irreversible inhibitor of the plasma membrane
      Ca(2+)-ATPase. The complex inhibited with similar efficiency the Ca(2+)-dependent
      ATPase and the phosphatase activities as well as the enzyme phosphorylation by
      ATP. The inhibition proceeded slowly (T(1/2)=30 min at 37 degrees C) with a
      K(i)=28+/-9 microM. The inclusion of ATP, ADP or AMPPNP in the inhibition medium
      effectively protected the enzyme against the inhibition, whereas ITP, which is
      not a PMCA substrate, did not. The rate of inhibition was strongly dependent on
      the presence of Mg(2+) but unaltered when Ca(2+) was replaced by EGTA. In spite
      of the similarities with the inhibition of other P-ATPases, no apparent Ca(2+)
      occlusion was detected concurrent with the inhibition by CrATP. In contrast,
      inhibition by the complex of La(3+) with ATP, LaATP, induced the accumulation of
      phosphoenzyme with a simultaneous occlusion of Ca(2+) at a ratio close to 1.5
      mol/mol of phosphoenzyme. The results suggest that the transport of Ca(2+)
      promoted by the plasma membrane Ca(2+)-ATPase goes through an enzymatic phospho
      intermediate that maintains Ca(2+) ions occluded from the media. This
      intermediate is stabilized by LaATP but not by CrATP.

PMID- 15975547
TI  - Iron deficiency induces a chlorophyll d-binding Pcb antenna system around
      Photosystem I in Acaryochloris marina.
AB  - The prochlorophyte-like cyanobacterium Acaryochloris marina contains two pcb
      genes, pcbA and pcbC, which encode chlorophyll (Chl) d-binding antenna proteins
      PcbA and PcbC, respectively. Using real-time reverse transcriptase polymerase
      chain reaction (RT-PCR), it is shown that when Acaryochloris cells are grown in
      an iron-deficient medium, the transcription of the pcbC gene is up-regulated
      compared to that of pcbA. Biochemical and immunological analyses indicated that
      under the same iron-deficient conditions, the level of Photosystem I (PSI)
      decreased compared with that of Photosystem II (PSII). Electron microscopy
      revealed that concomitant with these changes was the formation of Pcb-PSI
      supercomplexes which, in their largest form, were composed of 18 Pcb subunits
      forming a ring around the trimeric PSI reaction centre core. Mass spectrometry
      indicated that the PcbC protein is the main constituent of this outer PSI antenna
      system. It is therefore concluded that in Acaryochloris, the PcbC protein forms
      an antenna for PSI when iron levels become limiting and in this way compensates
      for the drop in the level of PSI relative to PSII which occurs under these
      conditions.

PMID- 15975548
TI  - Diffusion measurements of water, ubiquinone and lipid bilayer inside a
      cylindrical nanoporous support: a stimulated echo pulsed-field gradient MAS-NMR
      investigation.
AB  - Stimulated echo pulsed-field gradient 1H magic angle spinning NMR has been used
      to investigate the mobility of water, ubiquinone and tethered phospholipids,
      components of a biomimetic model membrane. The diffusion constant of water
      corresponds to an isotropic motion in a cylinder. When the lipid bilayer is
      obtained after the fusion of small unilamellar vesicles, the extracted value of
      lipid diffusion indicates unrestricted motion. The cylindrical arrangement of the
      lipids permits a simplification of data analysis since the normal bilayer is
      perpendicular to the gradient axis. This feature leads to a linear relation
      between the logarithm of the attenuation of the signal intensity and a factor
      depending on the gradient strength, for lipids covering the inner wall of
      aluminium oxide nanopores as well as for lipids adsorbed on a polymer sheet
      rolled into a cylinder. The effect of the bilayer formation on water diffusion
      has also been observed. The lateral diffusion coefficient of ubiquinone is in the
      same order of magnitude as the lipid lateral diffusion coefficient, in agreement
      with its localization within the bilayer.

PMID- 15975549
TI  - Hypoxia inhibits adipocyte differentiation in a HDAC-independent manner.
AB  - Oxygen is the most important factor for the appropriate regulation of multiple
      energy homeostasis and cell differentiation. Although hypoxia-induced signaling
      cascades have been intensively studied, the molecular mechanism by which hypoxic
      signals suppress adipocyte differentiation is unclear. Here, we demonstrated that
      repression of adipocyte differentiation by hypoxia and HIF1alpha- or Stra13
      overexpression was not associated with HDACs. Furthermore, HDACs did not affect
      inhibitory effect of Stra13 on PPARgamma promoter activity, although the hypoxia
      induced suppression of adipogenesis was accompanied with reduced acetylation of
      histone H3 and H4 at the PPARgamma promoter. Instead, we revealed that hypoxic
      circumstances biphasically activated AMPK and concomitantly blocked clonal
      expansion of preadipocytes, which is an indispensable step for early phase of
      adipocyte differentiation. Taken together, these results suggest that hypoxic
      condition attenuates adipocyte differentiation by inhibition of PPARgamma
      expression in a HDAC-independent manner and by activation of AMPK which impairs
      clonal expansion phase.

PMID- 15975550
TI  - Cell cycle synchronization of embryonic stem cells: effect of serum deprivation
      on the differentiation of embryonic bodies in vitro.
AB  - Research on stem-cell transplantation has indicated that the success of
      transplantation largely depends on synchronizing donor cells into the G0/G1
      phase. In this study, we investigated the profile of embryonic stem (ES) cell
      synchronization and its effect on the formation of embryonic bodies (EBs) using
      cell culture with serum deprivation. The D3 cell line of ES cells was used, and
      parameters such as cell proliferation and activity, EB formation, and expression
      of stage-specific embryonic antigen-1 and Oct-4 were investigated. Results showed
      that the percentage of G0/G1 stage in serum deprivation culture is significantly
      higher than that in culture with serum supplementation. Synchronized ES cells can
      reenter the normal cell cycle successfully after serum supply. EBs formed from
      synchronized ES cells have higher totipotency capability to differentiate into
      functional neuronal cells than EBs formed from unsynchronized ES cells. Our study
      provides a method for ES treatment before cell transplantation that possibly
      helps to decrease the rate of cell death after transplantation.

PMID- 15975551
TI  - alpha(1)-Agonists-induced Mg(2+) efflux is related to MAP kinase activation in
      the heart.
AB  - The stimulation of the alpha(1)-adrenergic receptor with phenylephrine results in
      the significant extrusion of Mg(2+) from the rat heart and cardiomyocytes.
      Phenylephrine-induced Mg(2+) extrusion is prevented by the removal of
      extracellular Ca(2+) or by the presence of Ca(2+)-channel blockers such as
      verapamil, nifedipine, or (+)BAY-K8644. Mg(2+) extrusion is almost completely
      inhibited by PD98059 (a MAP kinase inhibitor). The simultaneous addition of 5mM
      Ca(2+) and phenylephrine increases the extrusion of Mg(2+) from perfused hearts
      and cardiomyocytes. This Mg(2+) extrusion is inhibited by more than 90% when the
      hearts are preincubated with PD98059. ERKs are activated by perfusion with either
      phenylephrine or 5mM Ca(2+). This ERK activation is inhibited by PD98059.
      Overall, these results suggest that stimulating the cardiac alpha(1)-adrenergic
      receptor by phenylephrine causes the extrusion of Mg(2+) via the Ca(2+)
      activated, Na(+)-dependent transport pathway, and the ERKs assists in Mg(2+)
      transport in the heart.

PMID- 15975552
TI  - Histone peptide AKRHRK enhances H(2)O(2)-induced DNA damage and alters its site
      specificity.
AB  - Histone proteins are involved in compaction of DNA and the protection of cells
      from oxygen toxicity. However, several studies have demonstrated that the metal
      binding histone reacts with H(2)O(2), leading to oxidative damage to a
      nucleobase. We investigated whether histone can accelerate oxidative DNA damage,
      using a minimal model for the N-terminal tail of histone H4, CH(3)CO-AKRHRK
      CONH(2), which has a metal-binding site. This histone peptide enhanced DNA damage
      induced by H(2)O(2) and Cu(II), especially at cytosine residues, and induced
      additional DNA cleavage at the 5'-guanine of GGG sequences. The peptide also
      enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and ESR spin
      trapping signal from H(2)O(2) and Cu(II). Cyclic redox reactions involving
      histone-bound Cu(II) and H(2)O(2), may give rise to multiple production of
      radicals leading to multiple hits in DNA. It is noteworthy that the histone H4
      peptide with specific sequence AKRHRK can cause DNA damage rather than protection
      under metal-overloaded condition.

PMID- 15975553
TI  - A new elongase selectively expressed in Drosophila male reproductive system.
AB  - We have identified an elongase gene, elo68alpha, which is specifically
      transcribed in males. We have characterized the elo68alpha open reading frame,
      expressed it in fasDelta elo1Delta yeast and showed that it could elongate
      myristoleic and palmitoleic acids, therefore sharing an Elo1 specificity. This
      elongase was found to be exclusively expressed in male genital system (testis and
      ejaculatory bulb). Northern blot analysis showed that the elo68alpha gene was
      inducible at low temperatures. One P-strain mutant for elo68alpha and three
      excision lines for this P-element were subsequently studied. The excision line
      with only 1% elo68alpha expression showed decreased levels of vaccenyl acetate, a
      male pheromone produced in the ejaculatory bulb. The induction of elo68alpha
      expression at 21 degrees C was also paralleled with higher vaccenyl acetate
      production. These results strongly suggest that elo68alpha is involved in the
      elongation of short unsaturated fatty acids in males and might play a role in
      vaccenyl acetate biosynthesis.

PMID- 15975554
TI  - Dimethyl sulfoxide targets phage RNA polymerases to promote transcription.
AB  - Dimethyl sulfoxide (DMSO) is a "universal" solvent in pharmaceutical sciences and
      cell biology. DMSO was previously reported to facilitate in vitro transcription
      of chromatin and supercoiled plasmid, with the underlying mechanism being
      attributed to the alteration of the template structure. Here, we demonstrated
      that low concentrations of DMSO significantly increase the phage polymerase
      catalyzed RNA synthesis when the naked and short PCR products were used as
      templates, suggesting that DMSO promotes transcription through additional
      mechanism(s). Interestingly, SP6 RNA polymerase was more sensitive to the DMSO
      stimulation than T7 RNA polymerase, suggesting that the polymerase is an
      important target for DMSO stimulation of RNA synthesis. Consistent with this
      finding, we also showed that DMSO dramatically elevated the RNA polymerase
      activity. This elevated activity is explained by altered polymerase structure as
      reflected by a change in intrinsic fluorescence. Furthermore, DMSO was shown to
      simultaneously accumulate both the abortive and full-length transcripts, leading
      us to conclude that the DMSO-altered polymerase structure primarily encodes an
      enhanced activity at the stage of transcription initiation. DMSO-induced
      alteration of the polymerase structure and function highlights a potentially
      generalized mechanism in interpreting the molecular action of this popular
      solvent.

PMID- 15975555
TI  - The analysis of X-chromosome inactivation-related gene expression from single
      mouse embryo with sex-determination.
AB  - Chromatin remodeling by histone and DNA modification is important for the
      initiation of X-chromosome inactivation (XCI). In this study, a thorough
      transcriptional analysis of five XCI-related genes was performed by single cell
      reverse-transcribed PCR. An analysis of the XCI-related gene (Xist, Tsix,
      SUV39H1, SET7, and DNMT1) expression was performed to investigate the initiation
      process of XCI from early mouse single embryo (1-cell, 2-cell, 4-cell, 8-cell,
      and blastocyst). Detection of the expression of Xist and Tsix from single 2-cell
      embryo was feasible, although the expression of those genes was very low in
      single 1-cell embryo. Transcription of those genes may be activated from single 2
      cell embryo. After determining the sex of single embryo by Y-chromosome-specific
      Zfy expression, we found that Tsix could be detected from both male and female
      single embryos, but it was only possible to detect Xist from female single
      embryo. XCI chromatin-remodeling genes, such as histone H3 methylation enzymes
      (SUV39H1 and SET7) and DNA methylation enzyme (DNMT1), were expressed during all
      early phases of embryogenesis. The expression of those genes in single embryo was
      not dependent on sex. Our study illustrated that the expression of these
      chromatin-remodeling genes, SUV39H1, DNMT1, and SET7, may be originated from germ
      cells, which were not dependent on zygotic activation of Xist from female single
      embryo.

PMID- 15975556
TI  - Characterization of RAB-like4, the first identified RAB-like protein from
      Trypanosoma cruzi with GTPase activity.
AB  - RAB proteins, which belong to the RAS superfamily, regulate exocytic and
      endocytic pathways of eukaryotic cells, controlling vesicle docking and fusion.
      Few RAB proteins have been identified in parasites. Molecular markers for
      cellular compartments are important to studies concerning about the protein
      traffic in Trypanosoma cruzi, the causal agent of Chagas disease. In this work,
      we describe the characterization of TcRABL4, the first RAB-like gene identified
      in T. cruzi (GenBank Accession No.: ), present as a single-copy gene. TcRABL4
      contains all five consensus RAB motifs but lacks cysteine residues at the C
      terminus, which are essential to isoprenylation, an absolute prerequisite for
      membrane association of these proteins. TcRABL4 is a functional GTPase that is
      able to bind and hydrolyze GTP, and its gene is transcribed as a single 1.2 kb
      mRNA in epimastigotes. TcRABL4 appears to be differentially regulated in the
      three cell forms of the parasite, and the protein is not associated to membranes,
      unlike other RAB proteins. It is possible that TcRABL4 may be a member of a novel
      family of small GTPases.

PMID- 15975557
TI  - Probing the mechanism of rubredoxin thermal unfolding in the absence of salt
      bridges by temperature jump experiments.
AB  - Rubredoxins are the simplest type of iron-sulphur proteins and in recent years
      they have been used as model systems in protein folding and stability studies,
      especially the proteins from thermophilic sources. Here, we report our studies on
      the rubredoxin from the hyperthermophile Methanococcus jannaschii (T opt = 85
      degrees C), which was investigated in respect to its thermal unfolding kinetics
      by temperature jump experiments. Different spectroscopic probes were used to
      monitor distinct structural protein features during the thermal transition: the
      integrity of the iron-sulphur centre was monitored by visible absorption
      spectroscopy, whereas tertiary structure was followed by intrinsic tryptophan
      fluorescence and exposure of protein hydrophobic patches was sensed by 1
      anilinonaphthalene-8-sulphonate fluorescence. The studies were performed at
      acidic pH conditions in which any stabilising contributions from salt bridges are
      annulled due to protonation of protein side chain groups. In these conditions, M.
      jannaschii rubredoxin assumes a native-like, albeit more flexible and open
      conformation, as indicated by a red shift in the tryptophan emission maximum and
      1-anilinonaphthalene-8-sulphonate binding. Temperature jumps were monitored by
      the three distinct techniques and showed that the protein undergoes thermal
      denaturation via a simple two step mechanism, as loss of tertiary structure,
      hydrophobic collapse, and disintegration of the iron-sulphur centre are
      concomitant processes. The proposed mechanism is framed with the multiphasic one
      proposed for Pyrococcus furiosus rubredoxin, showing that a common thermal
      unfolding mechanism is not observed between these two closely related
      thermophilic rubredoxins.

PMID- 15975558
TI  - Calpain cleavage regulates the protein stability of p73.
AB  - The function of p73, a transcription factor belonging to the p53 family, is
      finely regulated by its steady-state protein stability. p73 protein
      degradation/stabilization can be regulated by mechanisms in part dependent on the
      ubiquitin proteasome system (UPS): (i) Itch/NEDD4-like UPS degradation, (ii)
      NEDD8 UPS degradation, and (iii) NQO1 20S proteasome-dependent (but ubiquitin
      independent) breakdown. Here, we show that, in vitro, Calpain I can cleave p73 at
      two distinct sites: the first proline-rich region and within the oligomerization
      domain. Consequently, different p73 isoforms can be degraded by calpains, i.e.,
      both N-terminal isoforms (TAp73 and DeltaNp73) as well as the C-terminal isoforms
      (alpha, beta, gamma, delta). Moreover, overexpression of the specific endogenous
      calpain inhibitor, calpastatin, in cultured cells increased the steady-state p73
      level. This suggests that calpains may play a physiological role in the
      regulation of p73 protein stability.

PMID- 15975559
TI  - C-reactive protein decreases expression of VEGF receptors and neuropilins and
      inhibits VEGF165-induced cell proliferation in human endothelial cells.
AB  - C-reactive protein (CRP) is associated with cardiovascular disease. However, its
      biological functions for the vascular system are largely unknown. The objective
      of this study was to determine whether CRP could affect endothelial cell
      proliferation and expression of VEGF receptors (VEGFRs) and/or neuropilins. Human
      coronary artery endothelial cells (HCAECs) treated with CRP showed a significant
      reduction of mRNA levels of VEGFR-2, VEGFR-3, NRP-1, and NRP-2 by 34%, 63%, 41%,
      and 43%, respectively, as compared to untreated control cells (p < 0.05) by real
      time PCR analysis. In addition, VEGF165-induced cell proliferation was determined
      by [3H]thymidine incorporation and MTS assay as well as capillary-like tube
      formation on Matrigel. HCAECs pretreated with CRP significantly decreased VEGF165
      induced [3H]thymidine incorporation by 73%, MTS absorbance by 44%, and capillary
      like tube formation by 54% as compared to CRP-untreated cells (p < 0.05). These
      data demonstrate that CRP significantly attenuates VEGF165-induced HCAEC
      proliferation and capillary-like tube formation through downregulation of
      expression of VEGFRs and NRPs. This study suggests a new molecular mechanism
      underlying the adverse effect of CRP on the vascular system.

PMID- 15975560
TI  - Brain cholinergic vulnerability: relevance to behavior and disease.
AB  - The major populations of cholinergic neurons in the brain include two
      "projection" systems, located in the pontine reticular formation and in the basal
      forebrain. These two complexes comprise, in part, the anatomical substrates for
      the "ascending reticular activating system" (ARAS). The pontine cholinergic
      system relays its rostral influences mainly through thalamic intralaminar nuclei,
      but it also connects to the basal forebrain and provides a minor innervation of
      cortex. The basal forebrain cholinergic complex (BFCC) projects directly to
      cortex and hippocampus, and has a minor connection with the thalamus. Recent data
      reveal that a parallel system of basal forebrain GABAergic projection neurons
      innervates cortex/hippocampus in a way that seems to complement the BFCC.
      Generally, the picture developed from more than 50 years of research is
      consistent with a "global" influence of these two ascending cholinergic
      projections on cortical and hippocampal regions. Seemingly, the BFCC acts in
      tandem or in parallel with the pontine cholinergic projection to activate the
      electro-encephalogram, increase cerebral blood flow, regulate sleep-wake cycling,
      and modulate cognitive function. There are quite a number and variety of human
      brain conditions, notably including Alzheimer's disease, in which degeneration of
      basal forebrain cholinergic neurons has been documented. Whether the corticopetal
      GABA system is affected by disease has not been established. Studies of
      degeneration of the pontine projection are limited, but the available data
      suggest that it is relatively preserved in Alzheimer's disease. Hypotheses of
      BFCC degeneration include growth factor deprivation, intracellular calcium
      dysfunction, amyloid excess, inflammation, and mitochondrial
      abnormalities/oxidative stress. But, despite considerable research conducted over
      several decades, the exact mechanisms underlying brain cholinergic vulnerability
      in human disease remain unclear.

PMID- 15975561
TI  - The role of calcineurin in amyloid-beta-peptides-mediated cell death.
AB  - Amyloid beta-peptide (Abeta) is widely held to be associated with Alzheimer's
      disease. It was previously demonstrated by our group that Abeta induces cell
      death by an apoptotic process. We report here that activation of the caspase-3
      apoptotic cascade is regulated by calcineurin-mediated BAD dephosphorylation.
      Calcineurin inhibitors were also proven to be effective by preventing the loss of
      mitochondrial membrane potential (Delta Psim) induced by Abeta, not allowing
      cytochrome c release from mitochondria and subsequently caspase-3 activation.
      Considering the results presented, we argue that calcineurin activation and BAD
      dephosphorylation are upstream in premitochondrial signaling events leading to
      caspase-3 activation in Abeta-peptide-treated cells.

PMID- 15975562
TI  - CNS neurons with links to both mood-related cortex and sympathetic nervous
      system.
AB  - Cardiovascular changes occur during mental stress and in certain types of mood
      disorders. The neural basis for this phenomenon is unknown but it may be
      dependent on CNS neurons that provide branched projections to affective
      processing regions of the brain, such as the medial prefrontal cortex, and to the
      sympathetic outflow system. Because these putative neurons may be connected to
      these two target sites by chains of neurons, we performed double virus
      transneuronal tracing experiments and show here that a select subset of neurons
      in the medial preoptic nucleus (MPN), lateral hypothalamic area (LHA), and
      nucleus tractus solitarius (NTS) are co-linked to these two sites. Neurotensin
      MPN, orexin-containing LHA, and catecholamine NTS neurons were the major
      phenotypes involved in these projections. This novel class of neurons may
      coordinate cardiovascular changes seen in different emotional states.

PMID- 15975563
TI  - Theta activity in the waking EEG is a marker of sleep propensity in the rat.
AB  - In humans, EEG power in the theta frequency band (5-8 Hz) during quiet waking
      increases during sleep deprivation (SD), and predicts the subsequent homeostatic
      increase of sleep slow-wave activity (SWA; EEG power between 0.5 and 4.0 Hz).
      These findings indicate that theta power in waking is an EEG variable, which
      reflects the rise in sleep propensity. In rodents, a number of short sleep
      attempts, as well as SWA in the waking EEG increase in the course of SD, but
      neither variable predicts the subsequent homeostatic increase of EEG SWA during
      recovery sleep. To investigate whether there is an EEG marker for sleep
      propensity also in rodents, the EEG of the rat was recorded during 6 h SD in the
      first half of the light period (SDL, n = 7). During SDL, power of the waking EEG
      showed an increase in the delta (1.5-4 Hz) and low theta (5-6.5 Hz) band. Based
      on the neck muscle EMG, wakefulness was subdivided into active (high EMG
      activity) and quiet (low EMG activity) waking. During quiet waking, the theta
      peak occurred at 5.5 Hz, the frequency at which the increase of EEG power during
      SD was most pronounced. This increase was due to higher amplitude of theta waves,
      while wave incidence (frequency) was unchanged. Correlation analysis showed that
      the rise in EEG power in the 5-7 Hz band during SD predicted the subsequent
      enhancement of SWA in non-rapid eye movement sleep. The analysis of data of a
      further batch of rats which were sleep deprived for 6 h after dark onset (SDD, n
      = 7) revealed a significant increase in theta-wave amplitude during the SD and a
      tendency for a similar, positive correlation between the increase of theta power
      (5-7 Hz) and subsequent SWA. The results indicate that in rats, as in humans, a
      specific waking EEG frequency, i.e., theta power in quiet waking is a marker of
      sleep propensity.

PMID- 15975564
TI  - Arvanil, a hybrid endocannabinoid and vanilloid compound, behaves as an
      antihyperkinetic agent in a rat model of Huntington's disease.
AB  - The present study was designed to examine whether arvanil (N-arachidonoyl
      vanillyl-amide), an endocannabinoid/vanilloid structural "hybrid", might provide
      symptom relief in the rat model of Huntington's disease (HD) generated by
      bilateral intrastriatal application of 3-nitropropionic acid (3-NP), where
      previous evidence suggests that hybrid cannabinoid/vanilloid compounds might be
      effective. As expected, arvanil did reduce ambulation, stereotypic activity, and
      number of hole entries, and increased the inactivity, in control rats. It was
      also active in 3-NP-lesioned rats, where, despite its lowering effects on
      stereotypic activity and number of hole entries, arvanil reduced the hyperkinesia
      (increased ambulation) typical of these rats, and also increased the inactivity,
      these two effects being more moderate than those found in control rats. Arvanil
      caused its antihyperkinetic effects in 3-NP-lesioned rats presumably by enhancing
      excitatory transmission at the globus pallidus, since it increased glutamate
      content in this region. This contrasts with its effects in control rats where
      arvanil enhanced GABA transmission at the globus pallidus. In summary, arvanil
      does alleviate hyperkinesia typical of HD, although it also affects locomotion in
      normal rats. Nevertheless, considering the lack of efficacious pharmacological
      treatments in this basal ganglia disorder, our findings might provide the basis
      for the development of more specific drugs against HD.

PMID- 15975565
TI  - Effects of GABAA receptor inhibition on response properties of barrel cortical
      neurons in C-fiber-depleted rats.
AB  - C-fiber depletion results in expansion of low threshold somatosensory
      mechanoreceptive fields. In this study, we investigated the role of intact C
      fibers in GABAA-mediated inhibition in barrel cortical neurons. We used
      electronically controlled mechanical stimulation of whiskers to quantitatively
      examine the responses of barrel cells to whisker displacements. After systemic
      injection of picrotoxin neuronal responses were recorded at 5 min intervals for
      20 min and then at 10 min intervals for 100 min. Picrotoxin injection caused a 3
      fold increase in response magnitude of adjacent whisker stimulation and 1.4-fold
      increase in response magnitude of principal whisker stimulation with a maximum
      enhancement 50 min after the injection. There was no significant change in
      spontaneous activity following picrotoxin injection. The response enhancement and
      receptive field expansion observed in normal rats were completely absent in the C
      fiber-depleted rats. These results suggest that the GABAA-mediated inhibition
      that modulates the receptive field functional organization of the barrel cortex
      depends on intact C-fibers.

PMID- 15975566
TI  - Structural analysis of xyloglucans in the primary cell walls of plants in the
      subclass Asteridae.
AB  - The structures of xyloglucans from several plants in the subclass Asteridae were
      examined to determine how their structures vary in different taxonomic orders.
      Xyloglucans, solubilized from plant cell walls by a sequential (enzymatic and
      chemical) extraction procedure, were isolated, and their structures were
      characterized by NMR spectroscopy and mass spectrometry. All campanulids
      examined, including Lactuca sativa (lettuce, order Asterales), Tenacetum
      ptarmiciflorum (dusty miller, order Asterales), and Daucus carota (carrot, order
      Apiales), produce typical xyloglucans that have an XXXG-type branching pattern
      and contain alpha-d-Xylp-, beta-D-Galp-(1-->2)-alpha-D-Xylp-, and alpha-L-Fucp-(1
      ->2)-beta-D-Galp-(1-->2)-alpha-D-Xylp- side chains. However, the lamiids produce
      atypical xyloglucans. For example, previous analyses showed that Capsicum annum
      (pepper) and Lycopersicon esculentum (tomato), two species in the order
      Solanales, and Olea europaea (olive, order Lamiales) produce xyloglucans that
      contain arabinosyl and galactosyl residues, but lack fucosyl residues. The XXGG
      type xyloglucans produced by Solanaceous species are less branched than the XXXG
      type xyloglucan produced by Olea europaea. This study shows that Ipomoea pupurea
      (morning glory, order Solanales), Ocimum basilicum (basil, order Lamiales), and
      Plantago major (plantain, order Lamiales) all produce xyloglucans that lack
      fucosyl residues and have an unusual XXGGG-type branching pattern in which the
      basic repeating core contains five glucose subunits in the backbone. Furthermore,
      Neruim oleander (order Gentianales) produces an XXXG-type xyloglucan that
      contains arabinosyl, galactosyl, and fucosyl residues. The appearance of this
      intermediate xyloglucan structure in oleander has implications regarding the
      evolutionary development of xyloglucan structure and its role in primary plant
      cell walls.

PMID- 15975567
TI  - Enhanced cardiac function in mice overexpressing protein phosphatase Inhibitor-2.
AB  - OBJECTIVE: Protein phosphatase 1 (PP1) has been implicated in the control of
      cardiac function. Cardiac specific overexpression of the catalytic subunit, PP1c,
      results in hypertrophy and depressed contractility. METHODS: To further address
      the role of PP1, transgenic mice (TG) were generated that overexpress in heart a
      functional COOH-terminally truncated form (amino acids 1-140) of the PP1
      inhibitor-2 (I-2(140)). RESULTS: The TG hearts show increased levels of I-2(140)
      mRNA as well as protein and activity. No increase in absolute or relative heart
      weight was observed, nor any changes in gross pathology or increase in morbidity
      or mortality in the TG mice. Immunohistochemical and biochemical analyses
      revealed that expression of the I-2(140) protein is confined to cardiomyocytes
      where it is mainly localized in the cytosol. The total protein phosphatase (PP)
      activity was reduced by 80% in TG hearts as compared to wild-type littermates
      (WT). The PP1c mRNA level was the same in TG and WT, while the protein level was
      increased by approximately 7-fold in TG animals. The maximal rates of contraction
      (+dP/dt) and of relaxation (-dP/dt) were increased by 32% and 40%, respectively,
      in the intact catheterized TG mice compared to WT. However, the maximal
      contractile response to beta-adrenergic agonists was comparable in hearts from TG
      and WT mice. In isolated cardiomyocytes of TG mice, Ca2+transient amplitude was
      increased by 50% under basal conditions and by 60% upon rapid caffeine
      application. The phospholamban (PLB) protein level was unchanged whereas the
      basal phosphorylation of PLB at Ser(16) was significantly increased in TG hearts.
      CONCLUSION: These results indicate that I-2(140) overexpression results in
      decreased PP1 activity and enhanced contractility in the heart, underscoring the
      fundamental role of PP1 in cardiac function.

PMID- 15975568
TI  - Extra- and intracellular ice formation in mouse oocytes.
AB  - The occurrence of intracellular ice formation (IIF) during freezing, or the lack
      there of, is the single most important factor determining whether or not cells
      survive cryopreservation. One important determinant of IIF is the temperature at
      which a supercooled cell nucleates. To avoid intracellular ice formation, the
      cell must be cooled slowly enough so that osmotic dehydration eliminates nearly
      all cell supercooling before reaching that temperature. This report is concerned
      with factors that determine the nucleation temperature in mouse oocytes. Chief
      among these is the concentration of cryoprotective additive (here, glycerol or
      ethylene glycol). The temperature for IIF decreases from -14 degrees C in
      buffered isotonic saline (PBS) to -41 degrees C in 1M glycerol/PBS and 1.5M
      ethylene glycol/PBS. The latter rapidly permeates the oocyte; the former does
      not. The initial extracellular freezing at -3.9 to -7.8 degrees C, depending on
      the CPA concentration, deforms the cell. In PBS that deformation often leads to
      IIF; in CPA it does not. The oocytes are surrounded by a zona pellucida. That
      structure appears to impede the growth of external ice through it, but not to
      block it. In most cases, IIF is characterized by an abrupt blackening or flashing
      during cooling. But in some cases, especially with dezonated oocytes, a pale
      brown veil abruptly forms during cooling followed by slower blackening during
      warming. Above -30 degrees C, flashing occurs in a fraction of a second. Below 
      30 degrees C, it commonly occurs much more slowly. We have observed instances
      where flashing is accompanied by the abrupt ejection of cytoplasm. During
      freezing, cells lie in unfrozen channels between the growing external ice. From
      phase diagram data, we have computed the fraction of water and solution that
      remains unfrozen at the observed flash temperatures and the concentrations of
      salt and CPA in those channels. The results are somewhat ambiguous as to which of
      these characteristics best correlates with IIF.

PMID- 15975569
TI  - Panicolytic-like effect induced by the stimulation of GABAA and GABAB receptors
      in the dorsal periaqueductal grey of rats.
AB  - Activation of GABA(A) and benzodiazepine receptors within the dorsal
      periaqueductal grey inhibits the escape behaviour evoked by the electrical
      stimulation of this midbrain area, a defensive reaction that has been related to
      panic. Nevertheless, there is no evidence indicating whether the same
      antiaversive effect is also observed in escape responses evoked by species
      specific threatening stimuli. In the present study, male Wistar rats were
      injected intra-dorsal periaqueductal grey with the benzodiazepine receptor
      agonist midazolam (10, 20 and 40 nmol), the GABA(A) receptor agonist muscimol (2,
      4 and 8 nmol), the GABA(B) receptor agonist baclofen (2, 4 and 8 nmol), or with
      the benzodiazepine inverse agonist FG 7142 (20, 40 and 80 pmol) and tested in an
      ethologically-based animal model of anxiety, the elevated T-maze. Besides escape,
      this test also allows the measurement of inhibitory avoidance which has been
      related to generalised anxiety disorder. Midazolam, muscimol and baclofen
      impaired escape, a panicolytic-like effect, without altering inhibitory
      avoidance. FG 7142, on the other hand, facilitated both avoidance and escape
      reactions, suggesting an anxiogenic and panicogenic-like effect, respectively.
      The data suggest that GABA(A)/benzodiazepine and GABA(B) receptors within the
      dorsal periaqueductal grey are involved in the control of escape behaviour and
      that a failure in this regulatory mechanism may be of importance in panic
      disorder.

PMID- 15975570
TI  - Inhibitory effects of putative peptidic urotensin-II receptor antagonists on
      urotensin-II-induced contraction of cat isolated respiratory smooth muscle.
AB  - Urotensin-II is purported to influence pulmonary function by modulating smooth
      muscle tone/growth. In the present study, Northern blot and reverse transcription
      polymerase chain reaction (RT-PCR) analysis indicated the presence of UT receptor
      mRNA in cat trachea, bronchi and lung parenchyma. Urotensin-II contracted cat
      isolated trachea and bronchi with similar potencies (pEC(50)s 8.61+/-0.07-8.81+/
      0.10). Contractile efficacies ranged from 19+/-9% to 63+/-11% KCl in the primary
      and secondary bronchi. The peptidic UT receptor antagonists BIM-23127, SB-710411
      and GSK248451 (7.18+/-0.12, 7.52+/-0.08 and 9.05+/-0.16 cat recombinant UT
      pK(i)s) inhibited urotensin-II-induced contraction of cat isolated trachea with
      pK(b)s 6.36+/-0.11, 6.74+/-0.07 and 9.27+/-0.12, respectively. As such, feline
      lung contains significant amounts of UT mRNA and this receptor appears to be
      functionally coupled to bronchoconstriction (the peptidic tool compound GSK248451
      representing a sub-nanomolar inhibitor of such effects). These findings suggest
      that the cat represents a suitable species for future studies designed to assess
      the effects of the urotensin-II receptor on pulmonary (patho)physiology.

PMID- 15975571
TI  - Protective effect of nitric oxide on ischemia/reperfusion-induced renal injury
      and endothelin-1 overproduction.
AB  - To elucidate the role of nitric oxide (NO) in the pathogenesis of ischemic acute
      renal failure, we examined the effects of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]
      5-nitro-3-hexenamide (FK409) and N(G)-nitro-L-arginine methyl ester (L-NAME) as a
      NO donor and a non-selective NO synthase inhibitor on ischemia/reperfusion
      induced renal injury and renal endothelin-1 content. Ischemic acute renal failure
      was induced by occlusion of the left renal artery and vein for 45 min followed by
      reperfusion, 2 weeks after contralateral nephrectomy. At 24 h after reperfusion,
      renal function in untreated acute renal failure rats markedly decreased and
      histological examination revealed severe renal damage. In addition, increases in
      renal endothelin-1 contents were evident in the acute renal failure rats at 2, 6,
      and 24 h after reperfusion, respectively. Pretreatment with FK409 (1 or 3 mg/kg,
      i.v.) attenuated ischemia/reperfusion-induced renal dysfunction, histological
      damage, and endothelin-1 overproduction after reperfusion. In contrast,
      pretreatment with L-NAME (1 or 10 mg/kg, i.v.) aggravated renal injuries of acute
      renal failure rats at 24 h after reperfusion, and the effect is accompanied by
      further increases in the renal endothelin-1 content at 2 and 6 h, but not at 24
      h, after reperfusion. These results suggest that suppressive effects of NO on the
      renal endothelin-1 overproduction induced by ischemia/reperfusion in an early
      phase are probably responsible for the protective effect of NO against ischemic
      acute renal failure.

PMID- 15975572
TI  - Streptozotocin-induced diabetes differentially modifies haloperidol- and gamma
      hydroxybutyric acid (GHB)-induced catalepsy.
AB  - To examine whether dopamine-mediated behavioral effects are altered in diabetes,
      this study compared the cataleptic effects of the dopamine receptor antagonist
      haloperidol (0.032-0.56 mg/kg) and gamma-hydroxybutyric acid (GHB; 56-1000 mg/kg)
      in control and streptozotocin (STZ)-treated rats. Haloperidol and GHB produced
      catalepsy in control and diabetic rats; haloperidol was less potent in diabetic
      rats (D(50)=0.44 mg/kg) than in controls (D(50)=0.19 mg/kg), while GHB was more
      potent in diabetic rats (D(50)=392 mg/kg) than in controls (D(50)=550 mg/kg). In
      diabetic rats, the non-competitive N-methyl-d-aspartate (NMDA) receptor
      antagonist dizocilpine (0.32 mg/kg) further attenuated haloperidol-induced
      catalepsy (D(50)=1.2 mg/kg) and further enhanced GHB-induced catalepsy (D(50)=248
      mg/kg). That haloperidol is less potent to produce catalepsy in diabetic rats is
      consistent with reports of altered dopamine receptor binding in diabetes.

PMID- 15975573
TI  - alpha(2)-Adrenoceptor involvement in the in vitro inhibitory effect of citalopram
      on a subpopulation of rat locus coeruleus neurons.
AB  - The aim of the present study was to investigate the modulation of locus coeruleus
      neurons by the selective serotonin (5-HT) reuptake inhibitor citalopram using
      single-unit extracellular recordings in rat brain slices. Citalopram inhibited
      the activity of a subpopulation of locus coeruleus neurons; thus 10 microM
      citalopram inhibited neurons by 53+/-17% (5 out of 15 cells), whereas the
      inhibition due to 100 microM was 64+/-4% (32 out of 42 cells). This effect was
      partially reversed (47+/-11%) by the alpha(2)-adrenoceptor antagonist idazoxan
      (10 microM), whereas it was unaffected by antagonists for 5-HT(1A), 5-HT(2,) and
      5-HT(3) receptors, and mu opioid receptors. 5-HT (50 or 200 microM), the 5-HT(1A)
      receptor agonist 8-OH-DPAT (+/-)-8-hydroxy-2-(DI-n-propyl-amino) tetralin
      hydrobromide, 10 microM) and the 5-HT(2) receptor agonist DOI ([+/-]-2,5-dimetoxy
      4-iodoamphetamine) hydrochloride, 10 or 30 microM) also inhibited a subpopulation
      of locus coeruleus cells. In addition, citalopram but not 5-HT, enhanced by 1.7
      fold the inhibitory effect of noradrenaline. Long-term treatment with citalopram
      (20 mg/kg/day) did not modify the effect of noradrenaline and bromoxidine. Taken
      together, our results indicate that citalopram exerts an inhibitory effect on
      locus coeruleus noradrenergic neurons. alpha(2)-adrenoceptor activation may
      underlie this effect as a result of elevated levels of noradrenaline in the
      synaptic cleft.

PMID- 15975574
TI  - Measurement of the propelled liquid by isolated hamster ileum as a parameter to
      evaluate peristalsis.
AB  - We present a method to measure the volume of liquid propelled by peristaltic
      movements of isolated hamster ileum as a novel means to assess peristaltic
      activity. The oral and aboral ends of the dissected ileum were attached to
      cannulas fixed horizontally. The application of intraluminal pressure by raising
      the level of liquid in the bottle connected to the oral end evoked peristalsis
      and intermittent propulsion of the intraluminal liquid. The inhibition of
      intrinsic neurons by tetrodotoxin stopped propulsion; this indicated that the
      liquid propulsion was correlated with neuron-regulated peristalsis. The volume of
      liquid propelled by one complete peristaltic movement was significantly greater
      than that by incomplete peristalsis, whereas recordings of pressure changes were
      indistinguishable. Inhibitors of nitric oxide synthase decreased the volume of
      liquid propelled by peristaltic movements, suggesting a role of nitrergic neurons
      in peristalsis. Our data show that the method described above might be suitable
      for analyzing peristalsis.

PMID- 15975575
TI  - EGFR enhances Survivin expression through the phosphoinositide 3 (PI-3) kinase
      signaling pathway.
AB  - The ErbB family of receptor tyrosine kinases includes the epidermal growth factor
      receptor (EGFR), p185/neu/c-erbB2, ErbB3, and ErbB4. Many of these receptors are
      overexpressed or amplified in various forms of cancers. Previous studies have
      indicated that activation of erbB molecules contributes to malignant
      transformation both by promoting cell proliferation through the mitogen-activated
      protein kinase (MAP kinase) signaling pathway and by preventing apoptosis through
      the Phosphoinositide 3 kinase (PI-3 kinase) pathway. Disabling erbB receptors
      converts malignant cells that were resistant to cell death caused by irradiation
      to cells that are sensitive to apoptosis. Here, we report that an activated form
      of EGFR can elevate the levels of Survivin, a member of the Inhibitor of
      Apoptosis Protein (IAP) family implicated in mitotic checkpoint control.
      Conversely, inactivation of the ErbB receptors reduces the expression levels of
      Survivin. Furthermore, we found that upregulation of Survivin by EGFR is
      dependent on the PI-3 kinase pathway but not on the MAP kinase pathway. Indeed,
      inhibition of PI-3 kinase can diminish Survivin at both the mRNA and the protein
      levels. Combined with previous findings that Survivin plays a role in control of
      chromosome segregation and that it is overexpressed in various cancers, our
      results suggest that EGFR may cause transformation by directly affecting mitosis
      and increasing chromosome instability.

PMID- 15975576
TI  - Mass spectroscopy identifies the splicing-associated proteins, PSF, hnRNP H3,
      hnRNP A2/B1, and TLS/FUS as interacting partners of the ZNF198 protein associated
      with rearrangement in myeloproliferative disease.
AB  - ZNF198 is fused with FGFR1 in an atypical myeloproliferative disease that results
      in constitutive activation of the kinase domain and mislocalization to the
      cytoplasm. We have used immunoprecipitation of a GFP-tagged ZNF198 combined with
      MALDI-TOF mass spectroscopy to identify interacting proteins. P splicing factor
      (PSF) was identified as one of the proteins and this interaction was confirmed by
      Western blotting. Other proteins identified were the spliceosomal components
      hnRNP A2/B1, hnRNP H3, and TLS/FUS. PSF is also known to interact with PTB,
      another member of the hnRNP family of proteins, and we further demonstrated that
      PTB interacts with ZNF198. The interaction between TLS/FUS and ZNF198 was
      confirmed using Western blot analysis. In 293 cells expressing the ZNF198/FGFR1
      fusion protein, neither PSF nor PTB binds to the fusion protein, possibly because
      of their differential localization in the cell.

PMID- 15975577
TI  - A role for complexes of survival of motor neurons (SMN) protein with gemins and
      profilin in neurite-like cytoplasmic extensions of cultured nerve cells.
AB  - Spinal muscular atrophy (SMA) is caused by reduced levels of SMN (survival of
      motor neurons protein) and consequent loss of motor neurons. SMN is involved in
      snRNP transport and nuclear RNA splicing, but axonal transport of SMN has also
      been shown to occur in motor neurons. SMN also binds to the small actin-binding
      protein, profilin. We now show that SMN and profilin II co-localise in the
      cytoplasm of differentiating rat PC12 cells and in neurite-like extensions,
      especially at their growth cones. Many components of known SMN complexes were
      also found in these extensions, including gemin2 (SIP-1), gemin6, gemin7 and
      unrip (unr-interacting protein). Coilin p80 and Sm core protein immunoreactivity,
      however, were seen only in the nucleus. SMN is known to associate with beta-actin
      mRNA and specific hnRNPs in axons and in neurite extensions of cultured nerve
      cells, and SMN also stimulates neurite outgrowth in cultures. Our results are
      therefore consistent with SMN complexes, rather than SMN alone, being involved in
      the transport of actin mRNPs along the axon as in the transport of snRNPs into
      the nucleus by similar SMN complexes. Antisense knockdown of profilin I and II
      isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN
      and its associated proteins in cytoplasmic aggregates. BIAcore studies
      demonstrated a high affinity interaction of SMN with profilin IIa, the isoform
      present in developing neurons. Pathogenic missense mutations in SMN, or deletion
      of exons 5 and 7, prevented this interaction. The interaction is functional in
      that SMN can modulate actin polymerisation in vitro by reducing the inhibitory
      effect of profilin IIa. This suggests that reduced SMN in SMA might cause axonal
      pathfinding defects by disturbing the normal regulation of microfilament growth
      by profilins.

PMID- 15975578
TI  - Advanced glycation end products induce death of retinal neurons via activation of
      nitric oxide synthase.
AB  - The purpose of this study was to determine whether advanced glycation end
      products (AGEs) are neurotoxic for cultured retinal neurons consisting mainly of
      amacrine cells, and to determine whether endogenous nitric oxide (NO) is involved
      in the toxicity. Cultured retinal neurons obtained from fetal Wistar rats
      (gestational age 19 days) were maintained in culture for 10 days, and then
      exposed to different concentrations of AGEs (0.02, 0.1, and 0.5 mg ml(-1)) in
      cultured media for different lengths of time. Both trypan blue exclusion and
      TUNEL assay were used to determine whether AGEs were neurotoxic, and NG-nitro-L
      arginine methyl ester (L-NAME, 500 microM), a nitric oxide synthase (NOS)
      inhibitor, was used to determine whether NO was involved. Immunohistochemical
      analyses were performed to determine whether specific receptors of AGEs (RAGE)
      are present on cultured retinal neurons; caspase-3 was activated, and 3
      nitrotyrosine was expressed on neurons treated with AGEs. Nitrite levels were
      measured in the supernatants of the media where neurons were incubated with AGEs.
      AGEs induced cell death in a time- and dose-dependent manner. TUNEL-positive
      cells and immunoreactivity to cleaved caspase-3 were enhanced on neurons
      following exposure to AGEs. L-NAME significantly suppressed the AGEs-induced
      neurotoxicity as assessed by both trypan blue exclusion and TUNEL assays.
      Activation of NOS was suggested by enhanced immunoreactivity to 3-nitrotyrosine
      on neurons and increased nitrite levels in the media incubated with AGEs. These
      results indicate that AGEs are neurotoxic to retinal neurons in culture through
      the activation of NOS. Apoptotic pathways may be in part involved in the death of
      the neurons.

PMID- 15975579
TI  - Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of the
      splice variants.
AB  - The effect on the stability of alternative transcripts of different mutations of
      the NDUFS4 gene in patients with Leigh syndrome with complex I deficiency is
      presented. Normally, two NDUFS4 splice variants are degraded by nonsense mediated
      mRNA decay (NMD) while a third form does not trigger NMD degradation. In a
      patient with a premature termination codon in exon 1, all the three splice
      variants are up-regulated. The present is the first case of a nonsense mutation
      leading to the abrogation of NMD, which can represent an additional event to be
      considered in the evaluation of clinically relevant mutations.

PMID- 15975580
TI  - hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells.
AB  - In Drosophila, the tumor suppressor Scribble is localized at the septate
      junctions of epithelial cells. Its mammalian homologue, hScrib, is a basolateral
      protein likely associated to proteins of the cell-cell junctions. We report the
      direct interaction between hScrib and ZO-2, a junction-associated protein. This
      interaction relies on two PDZ domains of hScrib and on the C-terminal motif of ZO
      2. Both proteins localise at cell-cell junctions of epithelial cells. A point
      mutation in the LRR of hScrib delocalises the protein from the plasma membrane
      and abrogates the interaction with ZO-2 but not with betaPIX. Tyrosine
      phosphorylation of hScrib does not impair the interaction with ZO-2. We show a
      direct link between two junctional proteins that are down-regulated during cancer
      progression.

PMID- 15975581
TI  - Anatomical considerations for percutaneous proximal humeral fracture fixation
      [Injury 2004;35:1133-6].

PMID- 15975582
TI  - HDL dysfunction in obstructive sleep apnea.
AB  - OBJECTIVE: HDL is anti-atherogenic and has antioxidant property. HDL dysfunction
      has been reported in patients with coronary heart disease and we hypothesize that
      HDL may also be dysfunctional in obstructive sleep apnea (OSA), a condition
      associated with increased oxidative stress. METHODS: 128 OSA patients and 82
      controls were recruited. HDL dysfunction was determined by evaluating the ability
      of HDL to inhibit LDL oxidation ex vivo. Plasma HDL was incubated with native LDL
      in the presence of dichlorofluorescein which fluoresced upon interaction with
      lipid oxidation products. Plasma levels of oxidized LDL and 8-isoprostane were
      measured by ELISA and a specific enzyme immunoassay, respectively. RESULTS:
      Plasma total 8-isoprostane levels were elevated in OSA subjects (p<0.01). Despite
      having similar concentrations of plasma lipids and apolipoproteins as controls,
      OSA subjects had greater degree of HDL dysfunction (p<0.01) and increased
      oxidized LDL levels (p<0.05). The apnea-hypopnea index was the main determinant
      of HDL dysfunction in OSA, accounting for 30% of its variance, with oxidized LDL
      and apolipoprotein AI contributing to 8% and 5% of its variance respectively
      (p<0.001). CONCLUSION: HDL is dysfunctional in preventing the formation and
      inactivation of oxidized lipids in OSA subjects and may partly contribute to
      their increased cardiovascular risk.

PMID- 15975583
TI  - Hibernating bears as a model for preventing disuse osteoporosis.
AB  - The hibernating bear is an excellent model for disuse osteoporosis in humans
      because it is a naturally occurring large animal model. Furthermore, bears and
      humans have similar lower limb skeletal morphology, and bears walk plantigrade
      like humans. Black bears (Ursus americanus) may not develop disuse osteoporosis
      during long periods of disuse (i.e. hibernation) because they maintain
      osteoblastic bone formation during hibernation. As a consequence, bone volume,
      mineral content, porosity, and strength are not adversely affected by annual
      periods of disuse. In fact, cortical bone bending strength has been shown to
      increase with age in hibernating black bears without a significant change in
      porosity. Other animals require remobilization periods 2-3 times longer than the
      immobilization period to recover the bone lost during disuse. Our findings
      support the hypothesis that black bears, which hibernate for as long as 5-7
      months annually, have evolved biological mechanisms to mitigate the adverse
      effects of disuse on bone porosity and strength.

PMID- 15975584
TI  - NO removal of Ni-electroplated activated carbon fibers.
AB  - In this study, activated carbon fibers (ACFs) were treated by a Ni-electroplating
      technique in order to remove nitric oxide (NO). The surface properties of the
      ACFs were investigated by XPS measurement. N2/77 K adsorption isotherm
      characteristics were determined by the BET equation. Also, NO-removal efficiency
      was confirmed by gas chromatography. For experimental results, Ni2p was
      introduced on ACFs during the Ni-electroplating technique. The nickel deposited
      on ACFs appeared to increase the NO removal despite the decrease in the BET
      specific surface areas and micropore volumes compared to nontreated ACFs.
      Consequently, it was found that NO conversion of ACFs was significantly improved
      due to the catalytic reaction of nickel deposited on ACFs.

PMID- 15975585
TI  - Ammonia removal of activated carbon fibers produced by oxyfluorination.
AB  - In this study, activated carbon fibers (ACFs) were produced by an oxyfluorination
      treatment to enhance the capacity of ammonia gas removal. The introduction of
      polar groups, such as CF, CO, and COOH, on the ACFs was confirmed by a XPS
      analysis, and N2/77 K adsorption isotherm characteristics including specific
      surface area and total and micropore volumes were studied by the BET and t-plot
      methods. The ammonia-removal efficiency was confirmed by a gas-detecting tube
      technique. As a result, the specific surface area and micropore volume of ACFs
      were slightly destroyed as the surface treatment time was increased. However, the
      oxyfluorinated ACFs led to an increase of fluorine and oxygen-containing polar
      functional groups in ACF surfaces, resulting in an increase in the ammonia
      removal efficiency of the ACFs produced.

PMID- 15975586
TI  - Permeability and thermodynamics study of quaternary ammonium surfactants
      phosphocholine vesicle system.
AB  - Quaternary ammonium compounds (QACs) are recognized as membrane active agents
      widely used as biocides. The main purpose of this work was to investigate the
      influence of the QAC head group and acyl chain length on their permeability
      perturbing power and on their affinity for lipidic membranes. Permeability
      perturbations were assessed by measuring the release of calcein entrapped inside
      vesicles. The affinity of QACs for bilayers was investigated by isothermal
      titration calorimetry (ITC). QACs bearing C(16) chain were found to be more
      efficient to decrease the membrane permeability than their C(12) analogues. On
      the other hand, the chemical nature of the ammonium head group has practically no
      influence on the permeability perturbations caused by QACs bearing C(16) chains.
      It was difficult to assess the partitioning of the QACs between the aqueous and
      lipid phases since the ITC signals could also be associated to morphological
      changes such as vesicle aggregation. For the systems for which reliable
      thermodynamic parameters could be obtained, the Gibbs energy of transfer was
      similar to that for the micellization. The entropy variation represented the main
      contribution to the Gibbs energy, indicating that the insertion of QACs inside
      lipidic bilayers is driven by hydrophobic interactions.

PMID- 15975587
TI  - Micellization of AOT in aqueous sodium chloride, sodium acetate, sodium
      propionate, and sodium butyrate media: a case of two different concentration
      regions of counterion binding.
AB  - Critical micelle concentrations of AOT in water in the presence of sodium
      chloride, sodium acetate, sodium propionate, and sodium butyrate were determined
      at 25 degrees C by the surface tension method. The co-ions do not have any effect
      on the value of critical micelle concentration. The surface density of AOT at the
      air-water interface increases in the presence of added electrolyte and attains a
      maximum value of 2.5+/-0.1 mol m-2 at a particular electrolyte concentration
      which is different for sodium chloride and the other three electrolytes. From the
      Corrin-Harkins plot it has been found that for AOT micelles the counterion
      binding constant has values 0.40 and 0.82 below and above approximately 0.015 mol
      kg-1 electrolyte concentration (c*), respectively. Measurement of sodium ion
      activity from the EMF method has confirmed such a shift in the counterion binding
      constant of AOT at c*. The higher value of the counterion binding constant for
      AOT has been reported for the first time. From fluorescence spectroscopy it has
      been found that the aggregation number of AOT is 22 in water and its average
      aggregation numbers in the presence of electrolytes are about 34 and 136 below
      and above c*, respectively. The increase by a factor of 2 in the counterion
      binding constant is shown to be due to a change in the shape of the AOT micelles
      around c*. The shape of AOT micelles in the electrolyte concentration range c* is
      inferred to be oblate spheroid and a change from this shape appears to occur
      above c*. A sudden increase in the polarity of the micelle-solution interface is
      also observed above c*.

PMID- 15975588
TI  - Solubilization of hydrophobic molecules in nanoparticles formed by polymer
      surfactant interactions.
AB  - The interaction between the anionic surfactant, sodium dodecyl sulfate, and the
      polyelectrolyte, poly(diallyldimethylammonium chloride), may lead to formation of
      nanoparticles dispersed in water. The morphology of the resulting nanoparticles
      and their ability to solubilize hydrophobic molecules were evaluated. As shown by
      SEM and AFM imaging, the particles are spherical, having a diameter of about 20
      nm. The solubilization within the nanoparticles was tested with pyrene, a
      fluorescence probe, and Nile Red, a solvatochromic probe. It was found that for
      Nile Red the solubilization within the nanoparticles is at lower polarity than
      for SDS micelles, and from pyrene solubilization it appears that the
      hydrophobicity of the nanoparticles depends on the ratio between the SDS
      molecules and the charge unit of the polymer.

PMID- 15975589
TI  - Minimizing losses of nonionic and anionic surfactants to a montmorillonite
      saturated with calcium using their mixtures.
AB  - Losses of surfactants through sorption to soils/sediments, especially to clay
      minerals, by various chemical interactions such as sorption and precipitation
      threaten the success of surfactant in enhancing remediation of contaminated soil
      and groundwater. In this study, the behavior of mixtures of a nonionic surfactant
      (TX-100) and an anionic surfactant (SDBS) sorbed to a montmorillonite saturated
      with calcium (Ca-montmorillonite) was investigated, and compared with that of
      individual surfactants. It is shown that the amounts of both TX-100 and SDBS
      sorbed to Ca-montmorillonite are significant. However, the amount of either TX
      100 or SDBS sorbed can be decreased and minimized when they are mixed with each
      other. Mixed micelle formation, which causes negative deviation of critical
      micelle concentrations (CMCs) from the ideal, is responsible for the decrease in
      sorbed TX-100 and sorbed SDBS in their mixtures. Because of their ability to
      minimize their amounts sorbed and thus enhance their active concentrations, as
      observed in mixed TX-100 and SDBS systems, mixed anionic-nonionic surfactants
      exhibit potential advantages in the area of enhanced soil and groundwater
      remediation.

PMID- 15975590
TI  - Phonological and morphological consistency in the acquisition of vowel duration
      spelling in Dutch and German.
AB  - In Dutch, vowel duration spelling is phonologically consistent but
      morphologically inconsistent (e.g., paar-paren). In German, it is phonologically
      inconsistent but morphologically consistent (e.g., Paar-Paare). Contrasting the
      two orthographies allowed us to examine the role of phonological and
      morphological consistency in the acquisition of the same orthographic feature.
      Dutch and German children in Grades 2 to 4 spelled singular and plural word forms
      and in a second task identified the correct spelling of singular and plural forms
      of the same nonword. Dutch children were better in word spelling, but German
      children outperformed the Dutch children in nonword selection. Also, whereas
      German children performed on a similar level for singular and plural items, Dutch
      children showed a large discrepancy. The results indicate that children use
      phonological and morphological rules from an early age but that the developmental
      balance between the two sources of information is constrained by the specific
      orthography.

PMID- 15975591
TI  - Spontaneous dissociation during functional MRI experiments.
AB  - It is assumed that the procedures of functional magnetic resonance imaging (fMRI)
      are able to provoke significant dissociative responses. Trait and state
      dissociation of 32 healthy subjects undergoing fMRI have been recorded. At least
      one-third of the subjects showed dissociative responses of very large effect size
      (d=4.10). The contributing causal factors for that dissociative response could
      not yet identified clearly. Considering the impact of dissociation on mental
      functions, we recommend controlling subjects undergoing fMRI studies for
      dissociative responses. Further studies on the actual phenomenological experience
      of subjects undergoing fMRI procedures are warranted.

PMID- 15975592
TI  - The effect of granulocyte macrophage-colony stimulating factor on bacterial
      translocation after administration of 5-fluorouracil in rats.
AB  - BACKGROUND: After surgical resection for colorectal carcinoma there is a high
      recurrence rate and, therefore, adjuvant chemotherapy may be useful in some
      patients. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent
      in the management of patients with colorectal cancer. However, gastrointestinal
      injury induced by chemotherapeutic agents may result in bacterial translocation
      from the gut into the systemic circulation. Granulocyte macrophage-colony
      stimulating factor (GM-CSF) may be used to prevent this side effect by means of
      macrophage activity stimulation. MATERIALS AND METHODS: A total of 45 rats were
      divided into three groups. Control group received intraperitoneal saline
      solution, 5-FU and GM-CSF groups received 50 mg/kg/day 5-FU intravenous infusion
      and GM-CSF group also received 200 ng/day GM-CSF subcutaneously for 6 days.
      Intestinal tissue was also sampled for pathological examination at day 7. Plasma
      levels of tumor necrosis factor-alpha and interleukin-6 were determined,
      bacterial translocation was quantified by lymph node, liver and spleen culture,
      and plasma endotoxin content was measured. RESULTS: White blood cell counts of
      the 5-FU rats were significantly lower than in the control and GM-CSF groups (P <
      0.01). The plasma endotoxin, tumor necrosis factor-alpha and interleukin-6 levels
      in the 5-FU and GM-CSF groups were significantly increased at day 7 compared with
      the control groups (P < 0.01), but these levels were significantly lower in the
      GM-CSF group compared to the 5-FU group (P < 0.01). 5-FU intervention caused
      significant increase in the frequencies of bacterial translocation at liver,
      spleen, mesenteric lymph node, and portal blood. Compared with 5-FU group, GM-CSF
      decreased the bacterial translocation (P < 0.01). CONCLUSIONS: This study
      observed that the administration of 5-FU resulted in bacterial translocation.
      Activation of inflammatory response with GM-CSF is highly effective in prevention
      of bacterial translocation in 5-FU interventions.

PMID- 15975593
TI  - Study of apoptosis and heat shock protein (HSP) expression in hepatocytes
      following radiofrequency ablation (RFA).
AB  - BACKGROUND: Radiofrequency ablation (RFA) of the liver produces necrosis of the
      hepatocytes. Histological examination shows a sharp demarcation between ablated
      and normal liver tissue. This experiment was carried out to study the cellular
      injury produced by RFA in area surrounding the ablated tissue and effect of
      reperfusion on this zone. MATERIAL AND METHODS: Five pigs underwent RFA of liver
      parenchyma. Four pigs were sacrificed 30 min after RFA and one pig was sacrificed
      5 days later. Ablated lesions including surrounding liver parenchyma was examined
      for apoptosis and HSP 70 expression. RESULTS: There was a zone of transition
      surrounding the necrotic ablated area that showed apoptosis as well as increased
      HSP 70 expression. This was more prevalent in the pig that was sacrificed 5 days
      later. CONCLUSION: RFA produces sub lethal injury in the zone of transition
      causing apoptosis and increase in HSP 70 expression. Increased HSP expression
      enhances immunogenicity of these cells that can have therapeutic implications for
      the treatment of liver.

PMID- 15975594
TI  - Mitochondrial DNA polymorphisms and risk of Parkinson's disease in Spanish
      population.
AB  - Mutations in mitochondrial DNA (mtDNA) have been implicated in the development of
      Parkinson's disease (PD). Mitochondrial function is necessary to supply the
      energy required for cell metabolism, and mutations in mitochondrial genes should
      have a deleterious effect in neuronal function. An association between several
      common mtDNA-polymorphisms and the risk of PD has been described. To test this
      association among Spanish patients, we genotyped 271 PD-patients and 230 healthy
      controls for 13 single-nucleotide polymorphisms (SNPs) through polymerase chain
      reaction (PCR) followed by digestion with a restriction enzyme. Alleles at eight
      of these SNPs define nine common European haplotypes, the mitochondrial
      haplogroups. In our population, no haplogroup showed significantly different
      frequencies between patients and controls. A significant association was found
      for the 4336T/C SNP (a polymorphism in the tRNA gln gene), with allele 4336C
      having a significantly increased frequency in PD-women compared to controls
      (OR=4.45; 95%CI=1.23-15.96; p=0.011). We also sequenced five of the complex I
      genes (ND1 to ND5) in the patients who were 4336C, and no mutation in these genes
      was found. We also found a significantly reduced frequency of 10398G in patients
      (p=0.009; OR=0.53), confirming a previously described protective effect for this
      allele in PD. In conclusion, we provided further evidence of the involvement of
      mitochondrial DNA variation in PD. In agreement with previous reports, we
      described a higher risk for PD among women with the mitochondrial 4336C allele in
      our population, and a protective effect for 10398G.

PMID- 15975595
TI  - "Man-in-the-barrel" syndrome as delayed manifestation of extrapontine and central
      pontine myelinolysis: beneficial effect of intravenous immunoglobulin.
AB  - "Man-in-the-barrel" syndrome has been rarely described following osmotic
      myelinolysis. We report a case of a 45-year-old woman admitted with septicemia
      and severe hyponatremia. She presented with a "man-in-the-barrel" syndrome which
      developed more than 10 days after rapid correction of the hyponatremia. There was
      radiological evidence of central pontine and extrapontine myelinolysis. Three
      days after completing a course of intravenous immunoglobulin therapy (0.4 g/kg
      body weight/day for 5 days) there was considerable improvement (Expanded
      Disability Status Scale score improved 30%). This case, reported for its peculiar
      mode of development, unusual presentation and challenging therapeutic response to
      intravenous immunoglobulin, highlights the enigmatic and unpredictable aspects of
      osmotic myelinolysis.

PMID- 15975596
TI  - A mathematical model of hematopoiesis--I. Periodic chronic myelogenous leukemia.
AB  - Periodic chronic myelogenous leukemia (PCML) is an interesting dynamical disease
      of the hematopoietic system in which oscillating levels of circulating
      leukocytes, platelets and/or reticulocytes are observed. Typically all of these
      three differentiated cell types have the same oscillation period, but the
      relation of the oscillation mean and amplitude to the normal levels is variable.
      Given the appearance of the abnormal Philadelphia chromosome in all of the
      nucleated progeny of the hematopoietic stem cells (HSCs), the most parsimonious
      conclusion is that chronic myelogenous leukemia, and its periodic variant, arise
      from derangements partially involving the dynamics of the stem cells. Here, we
      have synthesized several previous mathematical models of HSC dynamics, and models
      for the regulation of neutrophils, platelets and erythrocytes into a
      comprehensive model for the regulation of the hematopoietic system. Based on
      estimates of parameters for a typical normal human, we have systematically
      explored the changes in some of these parameters necessary to account for the
      quantitative data on leukocyte, platelet and reticulocyte cycling in 11 patients
      with PCML. Our results indicate that the critical model parameter changes
      required to simulate the PCML patient data are an increase in the amplification
      in the leukocyte line, an increase in the differentiation rate from the stem cell
      compartment into the leukocyte line, and the rate of apoptosis in the stem cell
      compartment. Our model system is particularly sensitive to changes in stem cell
      apoptosis rates, suggesting that changes in the numbers of proliferating stem
      cells may be important in generating PCML.

PMID- 15975598
TI  - The evolution of a Mullerian mimic in a spatially distributed community.
AB  - Strong positive density-dependence should lead to a loss of diversity, but
      warning-colour and Mullerian mimicry systems show extraordinary levels of
      diversity. Here, we propose an analytical model to explore the dynamics of two
      forms of a Mullerian mimic in a heterogeneous environment with two alternative
      model species. Two connected populations of a dimorphic, chemically defended
      mimic are allowed to evolve and disperse. The proportions of the respective model
      species vary spatially. We use a nonlinear approximation of Muller's number
      dependent equations to model a situation where the mortality for either form of
      the mimic decreases hyberbolically when its local density increases. A first non
      spatial analysis confirms that the positive density-dependence makes coexistence
      of mimetic forms unstable in a single isolated patch, but shows that mimicry of
      the rarer model can be stable once established. The two-patch analysis shows that
      when models have different abundance in different places, local mimetic diversity
      in the mimic is maintained only if spatial heterogeneity is strong, or, more
      interestingly, if the mimic is not too strongly distasteful. Therefore, mildly
      toxic species can become polymorphic in a wider range of ecological settings.
      Spatial dynamics thus reveal a region of Mullerian polymorphism separating
      classical Batesian polymorphism and Mullerian monomorphism along the mimic's
      palatability spectrum. Such polymorphism-palatability relationship in a spatial
      environment provides a parsimonious hypothesis accounting for the observed
      Mullerian polymorphism that does not require quasi-Batesian dynamics. While the
      stability of coexistence depends on all factors, only the migration rate and
      strength of selection appear to affect the level of diversity at the polymorphic
      equilibrium. Local adaptation is predicted in most polymorphic cases. These
      results are in very good accordance with recent empirical findings on the
      polymorphic butterflies Heliconius numata and H. cydno.

PMID- 15975597
TI  - A dynamical system model of neurofilament transport in axons.
AB  - We develop a dynamical system model for the transport of neurofilaments in axons,
      inspired by Brown's "stop-and-go" model for slow axonal transport. We use
      fast/slow time-scale arguments to lower the number of relevant parameters in our
      model. Then, we use experimental data of Wang and Brown to estimate all but one
      parameter. We show that we can choose this last remaining parameter such that the
      results of our model agree with pulse-labeling experiments from three different
      nerve cell types, and also agree with stochastic simulation results.

PMID- 15975599
TI  - [Ca2+] oscillations in a model of energy-dependent Ca2+ uptake by the endoplasmic
      reticulum.
AB  - Active Ca2+ transport in living cells necessitates controlled supply of metabolic
      energy. Direct coupling between sarco/endoplasmic reticulum (ER) Ca2+ ATPases
      (SERCA) and intracellular energy-generation sites has been well established
      experimentally. On the basis of these experimental findings we propose a pump
      driven model to investigate complex dynamic properties of a cell system. The
      model describes the pump process both by the Ca2+ ATPase itself and by a suitable
      description of the glycolysis. The associated set of differential equations shows
      a rich behavior, the solutions ranging from simple periodic oscillations to
      complex patterns such as bursting and spiking. Recent experimental results on
      calcium oscillations in Xenopus laevis oocytes and on dynamic patterns of
      intracellular Ca2+ concentrations in electrically non-excitable cells are well
      described by corresponding theoretical results derived within the proposed model.
      The simulation results are further compared to spontaneous [Ca2+] oscillations in
      primitive endodermal cells.

PMID- 15975600
TI  - An asymmetric parental investment conflict with continuous strategy sets.
AB  - In the parental investment conflict each of the sexes decides how much to invest
      in its brood, where its decision influences both sexes' fitness. In nature, each
      species is usually characterized by a common parental care pattern, male-only
      care, female-only care or biparental care. A possible way for understanding the
      factors that have led each species to adopt its unique parental care pattern is
      to analyse a male's and a female's decision process using a game-theoretical
      model. This paper suggests a two-stage game-theoretical model with two types of
      players, male and female. During the game each parent makes three decisions. The
      interval between the beginning of the game, i.e. after mating and having
      offspring, and the moment a parent starts to care for them is a random variable.
      Thus, in the first stage a parent chooses the cumulative probability distribution
      of this interval, and its amount of parental care. In the second stage the other
      parent chooses its probability for cooperation. It is assumed that as long as
      parental care is not provided the offspring are at risk, and that parental caring
      accrues a different cost for each sex. We compute the Evolutionary Stable
      Strategies (ESS) under payoff-relevant asymmetry, and show that uniparental and
      biparental care are possible ESS. We also characterize cases where the sex having
      the lower cost "forces" the sex having the higher cost to care and vice versa.

PMID- 15975601
TI  - Lethality and synthetic lethality in the genome-wide metabolic network of
      Escherichia coli.
AB  - Recent genomic analyses on the cellular metabolic network show that reaction flux
      across enzymes are diverse and exhibit power-law behavior in its distribution.
      While intuition might suggest that the reactions with larger fluxes are more
      likely to be lethal under the blockade of its catalysing gene products or gene
      knockouts, we find, by in silico flux analysis, that the lethality rarely has
      correlations with the flux level owing to the widespread backup pathways innate
      in the genome-wide metabolism of Escherichia coli. Lethal reactions, of which the
      deletion generates cascading failure of following reactions up to the biomass
      reaction, are identified in terms of the Boolean network scheme as well as the
      flux balance analysis. The avalanche size of a reaction, defined as the number of
      subsequently blocked reactions after its removal, turns out to be a useful
      measure of lethality. As a means to elucidate phenotypic robustness to a single
      deletion, we investigate synthetic lethality in reaction level, where
      simultaneous deletion of a pair of nonlethal reactions leads to the failure of
      the biomass reaction. Synthetic lethals identified via flux balance and Boolean
      scheme are consistently shown to act in parallel pathways, working in such a way
      that the backup machinery is compromised.

PMID- 15975603
TI  - The repair rate of radiation-induced DNA damage: a stochastic interpretation
      based on the gamma function.
AB  - There is a large body of evidence that stress-induced DNA damage may be
      responsible for cell lethality, cancer proneness and/or immune reaction. However,
      statistical features of their repair rate remain poorly documented. In order to
      interpret the shape of the radiation-induced DNA damage repair curves with a
      minimum of biological assumptions, we introduced the concept of repair
      probability, specific to any individual radiation-induced DNA damage, whatever
      its biochemical type. We strengthened the apparent paradox that the repair rate
      of a population of DNA damage is time-dependent even if the repair rate of the
      individual DNA damage is constant. Hence, the existing models, based on a dual
      approach of the DNA repair may be insufficient for describing the DNA repair rate
      over a large range of repair times. Since the repair probability of DNA damage
      cannot be assessed individually, the measurement of the DNA repair rate is
      assumed to consist in determining the instantaneous mean of all repair
      probabilities. The relevance of this model was examined with different endpoints:
      cell species, genotypes, radiation type and chromatin condensation. The Euler's
      Gamma function was shown to provide the distribution the most consistent with
      such hypotheses. Furthermore, formulas, deduced from the Gamma distribution, were
      found to be compatible with our previous model, empirically defined but based on
      a variable repair half-time.

PMID- 15975602
TI  - Insights to the minimal model of insulin secretion through a mean-field beta cell
      model.
AB  - The present work introduces an extension of the original minimal model of second
      phase insulin secretion during the intravenous glucose tolerance test (IVGTT),
      which can provide both physiological and mathematical insights to the minimal
      model. The extension is named the mean-field beta cell model since it returns the
      average response of a large number of nonlinear secretory entities. Several
      secretion models have been proposed for the IVGTT, and we shall identify two
      fundamentally different theoretical features of these models. Both features can
      play a central role during the IVGTT, including the one presented in the mean
      field beta cell model.

PMID- 15975604
TI  - Modeling polio as a disease of development.
AB  - Poliomyelitis is a disease which began to appear in epidemic proportions in the
      late 19th century, paradoxically, just at the time when living conditions and
      developments in health were transforming enormously for the better. We present a
      simple age-class model that explains this "disease of development" as a threshold
      phenomenon. Epidemics arise when improved conditions in hygiene are able to
      reduce disease transmission of polio amongst children below a critical threshold
      level. This generates a large susceptible adult population in which, under
      appropriate conditions, epidemics can propagate. The polio model is analysed in
      terms of its bifurcation properties and in terms of its non-equilibrium outbreak
      dynamics.

PMID- 15975605
TI  - A quantitative model for flow-induced bioluminescence in dinoflagellates.
AB  - A model is presented for the flash response of bioluminescent dinoflagellates
      stimulated by fluid shear. The model is based on the idea that the response of an
      individual cell to stimulation is inherently probabilistic, and can be modeled as
      a Poisson process over short time scales. A new cell parameter, the cell anxiety,
      is introduced to parameterize the probability of flashing. The statistical model
      is incorporated into a description of fully developed fluid flow in pipes and a
      cylindrical Couette chamber, and found to compare favorably with previously
      published data from experiments.

PMID- 15975607
TI  - A stochastic model of the distribution of unequal competitors between resource
      patches.
AB  - We present a stochastic model of individuals' movements between two patches of
      resources. The population is made up of two types of individual with differing
      competitive abilities, and two types of movements occur, with individuals moving
      either to increase their intake rate or at random. Several previous models have
      used simulations to evaluate the likely distribution of individuals. We instead
      derive equations for the equilibrium distribution of the population, which can be
      solved numerically. This avoids the need to choose an initial distribution for
      the population, and enables us to obtain the probability with which rare events
      occur. This may not be possible when simulations are used, since a rare event may
      not occur at all. We find that when random movements are rare, an increase in the
      rate of random movements out of a patch can increase the number of individuals on
      that patch. We consider an approximation to the model with rare random movements,
      which provides an explanation for this phenomenon.

PMID- 15975608
TI  - Selection, mutation and sexual reproduction in an infinite haploid population
      with a genome of finite length.
AB  - We present a model which describes mutation, selection and sexual reproduction in
      an infinite haploid population with a finite genome. Each generation is described
      using an approximation which assures a certain persistent form of the
      distribution of the number of deleterious elements. The steady state exists and
      is determined. In addition, we conclude that the introduction of sexual
      reproduction increases the mean fitness in the equilibrium.

PMID- 15975606
TI  - A mathematical model of hematopoiesis: II. Cyclical neutropenia.
AB  - Cyclical neutropenia is a dynamical disease of the hematopoietic system marked by
      an oscillation in circulating leukocyte (e.g. neutrophil) numbers to near zero
      levels and then back to normal. This oscillation is also mirrored in the
      platelets and reticulocytes which oscillate with the same period. Cyclical
      neutropenia has an animal counterpart in the grey collie. Using the mathematical
      model of the hematopoietic system of Colijn and Mackey [A mathematical model of
      hematopoiesis: I. Periodic chronic myelogenous leukemia. Companion paper to the
      present paper.] we have determined what parameters are necessary to mimic
      laboratory and clinical data on untreated grey collies and humans, and also what
      changes in these parameters are necessary to fit data during treatment with
      granulocyte colony stimulating factor (G-CSF). Compared to the normal steady
      state values, we found that the major parameter changes that mimic untreated
      cyclical neutropenia correspond to a decreased amplification (increased
      apoptosis) within the proliferating neutrophil precursor compartment, and a
      decrease in the maximal rate of re-entry into the proliferative phase of the stem
      cell compartment. For the data obtained during G-CSF treatment, good fits were
      obtained only when parameters were altered that would imply that G-CSF led to
      higher amplification (lower rate of apoptosis) in the proliferating neutrophil
      precursors, and a elevated rate of differentiation into the neutrophil line.

PMID- 15975609
TI  - Inferring gene networks from steady-state response to single-gene perturbations.
AB  - Inferring gene networks from gene expression data is an important step in
      understanding the molecular machinery of life. Three methods for establishing and
      quantifying causal relationships between genes based on steady-state measurements
      in single-gene perturbation experiments have recently been proposed: the
      regulatory strength method, the local regulatory strength method, and Gardner's
      method. The theoretical basis of these methods is presented here in a thorough
      and consistent fashion. In principle, for the same data set all three methods
      would generate identical networks, but they would quantify the strengths of
      connections in different ways. The regulatory strength method is shown here to be
      topology-dependent. It adopts the format of the data collected in gene expression
      microarray experiments and therefore can be immediately used with this
      technology. The regulatory strengths obtained by this method can also be used to
      compute local regulatory strengths. In contrast, Gardner's method requires both
      measurements of mRNA concentrations and measurements of the applied rate
      perturbations, which is not usually part of a standard microarray experimental
      protocol. The results generated by Gardner's method and by the two regulatory
      strengths methods differ only by scaling constants, but Gardner's method requires
      more measurements. On the other hand, the explicit use of rate perturbations in
      Gardner's approach allows one to address new questions with this method, like
      what perturbations caused given responses of the system. Results of the
      application of the three techniques to real experimental data are presented and
      discussed. The comparative analysis presented in this paper can be helpful for
      identifying an appropriate technique for inferring genetic networks and for
      interpreting the results of its application to experimental data.

PMID- 15975610
TI  - Piglet pial arteries respond to N-methyl-D-aspartate in vivo but not in vitro.
AB  - Controversy exists concerning whether activation of N-methyl-D-aspartate (NMDA)
      receptors exerts direct dilator effects on cerebral arteries. The purpose of this
      study was to examine the responses of isolated piglet arteries to NMDA to
      determine whether isolated arteries, apart from surrounding neuronal tissue, are
      capable of responding to NMDA. Piglet arteries (100-200 microm) were isolated
      from branches of the middle cerebral artery and carefully dissected free of
      adherent tissue. Arteries were then mounted in an arteriograph system and
      pressurized to either 30 mm Hg (n=8), 60 mm Hg (n=10), 80 mm Hg (n=6), or 100 mm
      Hg (n=5). After development of spontaneous tone, NMDA (10(-5) to 10(-3) M) was
      administered abluminally to the vessels, and no appreciable response was noted
      (for example; 10(-4) M, 30 mm Hg: 3+/-3% change in active diameter; 60 mm Hg: 
      4+/-3% change in active diameter). Following a thorough washout, vessels were
      treated with bradykinin (10(-9) to 10(-7) M), and the arteries did respond (10(
      7) M, 30 mm Hg: 26+/-3% change in active diameter; 60 mm Hg: 65+/-10% change in
      active diameter). In contrast, 10(-5) M and 10(-4) M NMDA dilated arteries in
      vivo by 9+/-2% and 29+/-6% change in active diameter, respectively (n=6). These
      results demonstrate that isolated cerebral arteries do not respond directly to
      NMDA receptor activation. This work confirms our previous in vivo data and is
      consistent with the hypothesis that cerebral arteries respond to NMDA through a
      secondary interaction mediated by neuronal release of NO and not to NMDA
      directly.

PMID- 15975611
TI  - Shortened telomeres in murine scid cells expressing mutant hRAD54 coincide with
      reduction in recombination at telomeres.
AB  - Murine severe combined immunodeficiency (scid) cells are characterized by
      defective Prkdc (DNA-PKcs), one of the key genes involved in the repair of DNA
      double-strand breaks. Interestingly, scid mice are not null mutants and their
      cells are likely to show low DNA-PKcs activity. Prkdc is also involved in
      telomere maintenance and in contrast to mice genetically engineered to lack Prkdc
      (i.e. null mutants), which show complete absence of DNA-PKcs activity, loss of
      telomere capping function and normal telomere length, cells from scid mice show
      not only loss of telomere capping function but also abnormally elongated
      telomeres. Here we demonstrate that telomere elongation observed in murine scid
      cells can be reversed by expressing mutant hRAD54, a protein involved in
      homologous recombination. In addition, we measured recombination rates at
      telomeres using chromosome orientation fluorescence in situ hybridization (CO
      FISH) and found that these are elevated in scid cells in comparison with control
      cells, or significantly reduced in scid cells expressing mutant hRAD54.
      Similarly, recombination rates at telomeres are reduced in scid cells following
      introduction of functional Prkdc. Since expression of mutant hRAD54 and
      restoration of functional Prkdc in scid cells cause the same effects, i.e.
      telomere shortening and reduced recombination rates at telomeres, these results
      argue that telomere elongation in scid cells is a complex trait resulting from
      interactions between homologous recombination mechanisms and DNA-PKcs.

PMID- 15975612
TI  - Outbreaks of cholera-like diarrhoea caused by enterotoxigenic Escherichia coli in
      the Brazilian Amazon Rainforest.
AB  - The relationship between enteropathogens and severe diarrhoea in the Brazilian
      Amazon is poorly understood. In 1998, outbreaks of acute diarrhoea clinically
      diagnosed as cholera occurred in two small villages localized far from the main
      cholera route in the Brazilian rainforest. PCR was performed on some
      enteropathogens and heat-labile (LT) and/or heat-stable (STh) toxin genes, the
      virulence determinants of enterotoxigenic Escherichia coli (ETEC), were detected.
      Further characterization of ETEC isolates revealed the presence of two clones,
      one from each outbreak. One presenting serotype O167:H5 harboured LT-I and STh
      toxin genes and expressed the CS5CS6 colonization factor. The other, a non
      typeable serotype, was positive for the LT-I gene and expressed the CS7
      colonization factor. The current study demonstrates the importance of molecular
      diagnosis in regions such as the Amazon basin, where the enormous distances and
      local support conditions make standard laboratory diagnosis difficult. Here we
      also show that the mis-identified cholera cases were in fact associated with ETEC
      strains. This is the first report of ETEC, molecularly characterized as the
      aetiological agent of severe diarrhoea in children and adults in the Brazilian
      Amazon Rainforest.

PMID- 15975613
TI  - Validation of in vitro cell models used in drug metabolism and transport studies;
      genotyping of cytochrome P450, phase II enzymes and drug transporter
      polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and
      colon carcinoma (CaCo-2, LS180) cell lines.
AB  - Human cell lines are often used for in vitro biotransformation and transport
      studies of drugs. In vivo, genetic polymorphisms have been identified in drug
      metabolizing enzymes and ABC-drug transporters leading to altered enzyme
      activity, or a change in the inducibility of these enzymes. These genetic
      polymorphisms could also influence the outcome of studies using human cell lines.
      Therefore, the aim of our study was to pharmacogenotype four cell lines
      frequently used in drug metabolism and transport studies, HepG2, IGROV-1, CaCo-2
      and LS180, for genetic polymorphisms in biotransformation enzymes and drug
      transporters. The results indicate that, despite the presence of some genetic
      polymorphisms, no real effects influencing the activity of metabolizing enzymes
      or drug transporters in the investigated cell lines are expected. However, this
      characterization will be an aid in the interpretation of the results of
      biotransformation and transport studies using these in vitro cell models.

PMID- 15975614
TI  - Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis
      in Zucker diabetic fatty rats: activation of PPAR-alpha.
AB  - Salacia oblonga (SO) root is an Ayurvedic medicine with anti-diabetic and anti
      obese properties. Peroxisome proliferator-activated receptor (PPAR)-alpha, a
      nuclear receptor, plays an important role in maintaining the homeostasis of lipid
      metabolism. Here, we demonstrate that chronic oral administration of the water
      extract from the root of SO to Zucker diabetic fatty (ZDF) rats, a genetic model
      of type 2 diabetes and obesity, lowered plasma triglyceride and total cholesterol
      (TC) levels, increased plasma high-density lipoprotein levels and reduced the
      liver contents of triglyceride, non-esterified fatty acids (NEFA) and the ratio
      of fatty droplets to total tissue. By contrast, the extract had no effect on
      plasma triglyceride and TC levels in fasted ZDF rats. After olive oil
      administration to ZDF the extract also inhibited the increase in plasma
      triglyceride levels. These results suggest that SO extract improves postprandial
      hyperlipidemia and hepatic steatosis in ZDF rats. Additionally, SO treatment
      enhanced hepatic expression of PPAR-alpha mRNA and protein, and carnitine
      palmitoyltransferase-1 and acyl-CoA oxidase mRNAs in ZDF rats. In vitro, SO
      extract and its main component mangiferin activated PPAR-alpha luciferase
      activity in human embryonic kidney 293 cells and lipoprotein lipase mRNA
      expression and enzyme activity in THP-1 differentiated macrophages; these effects
      were completely suppressed by a selective PPAR-alpha antagonist MK-886. The
      findings from both in vivo and in vitro suggest that SO extract functions as a
      PPAR-alpha activator, providing a potential mechanism for improvement of
      postprandial hyperlipidemia and hepatic steatosis in diabetes and obesity.

PMID- 15975615
TI  - Isolation and identification of (44-R,S)-44,55-dihydroxyyessotoxin from
      Protoceratium reticulatum, and its occurrence in extracts of shellfish from New
      Zealand, Norway and Canada.
AB  - 44,55-Dihydroxyyessotoxin (1) was isolated from extracts of Protoceratium
      reticulatum and identified by analysis of its one- and two-dimensional NMR and
      mass spectra. In addition, LC-MS methods revealed the presence of compounds
      tentatively identified as (44-R,S)-44,55-dihydroxy-41a-homoyessotoxin (2) and (44
      R,S)-44,55-dihydroxy-9-methyl-41a-homoyessotoxin (3). LC-MS analyses indicate
      that 1 is a constituent of P. reticulatum in New Zealand and Norway, and it was
      present in three species of mussels from New Zealand, Norway, and Canada.

PMID- 15975616
TI  - Effects of scorpion venom bioactive polypolypeptides on platelet aggregation and
      thrombosis and plasma 6-keto-PG F1alpha and TXB2 in rabbits and rats.
AB  - Effects of scorpion venom active polypeptide (SVAP) from scorpion venom of Buthus
      Martensii Karsch of Chinese on platelet aggregation in ex vivo and vitro in
      rabbits, thrombosis in carotid artery of rats and plasma 6-keto-PG F1alpha and
      TXB2 in rats were studied by the turbidimetry, the duplicated thrombosis model by
      electrostimulation and RIA, respectively. The results showed that SVAP 0.125,
      0.25, 0.5 mg/ml inhibited significantly the rabbit platelet aggregation triggered
      by 0.3 U/ml thrombin, 10 microM ADP in vitro (P<0.05 or 0.01) and SVAP at the
      dose of 0.32, 0.64 mg/kg iv prolonged distinctively the occlusion time of
      thrombosis that were induced by electrical stimulation. Increased% of 0.16, 0.32
      and 0.64 mg/kg were 30.16, 71.74, 98.27%, respectively, which showed a good dose
      effect relationship. SVAP 0.22 mg/ml (in vitro) or 0.2, 0.4 mg/kg (in ex vivo)
      could obviously increase the plasma concentration of 6-keto-PG F1alpha, but
      slightly effect rats plasma concentration of TXB2 in vitro and in ex vivo and
      significantly increase of value of PG I2/TXA2, which suggested that the mechanism
      of the antithrombotic action of SVAP is related to the resistance against
      platelet aggregation, increase of the concentration of PG I2 in plasma.

PMID- 15975617
TI  - Botulinum neurotoxin type A causes shifts in myosin heavy chain composition in
      muscle.
AB  - Botulinum neurotoxin type A has gained widespread use for treatment of a host of
      neuromuscular conditions. However, the potential effect of this toxin has on the
      histological and biochemical properties of skeletal muscle remains largely
      unexplored. The purpose of this study was to characterize the myosin heavy chain
      (MHC) distribution of adult rat skeletal muscle treated with botulinum neurotoxin
      type. Varying doses of the toxin were injected into the triceps surae muscle
      group of one hind limb. Force production was assessed periodically to access the
      functional deficit incurred. After 10 weeks, animals were sacrificed, muscles
      removed, and MHC composition determined. Body weight, muscle weight and force of
      the injected leg were significantly reduced in all groups, while loss of muscle
      weight and force in the contralateral leg was variable. In the injected plantaris
      and gastrocnemius muscles, type I MHC increased approximately 100%, while type
      IIa/x decreased approximately 50%. In the contralateral gastrocnemius, types I
      and IIa/x MHC increased approximately 100%, while type IIb decreased
      approximately 45%. These data suggest that botulinum neurotoxin causes shifts in
      MHC composition in injected and contralateral muscles that are contrary to those
      seen with denervation and similar to those seen with aging.

PMID- 15975618
TI  - Finite element modelling of a rotating piezoelectric ultrasonic motor.
AB  - The evaluation of the performance of ultrasonic motors as a function of input
      parameters such as the driving frequency, voltage input and pre-load on the rotor
      is of key importance to their development and is here addressed by means of a
      finite element three-dimensional model. First the stator is simulated as a fully
      deformable elastic body and the travelling wave dynamics is accurately
      reproduced; secondly the interaction through contact between the stator and the
      rotor is accounted for by assuming that the rotor behaves as a rigid surface.
      Numerical results for the whole motor are finally compared to available
      experimental data.

PMID- 15975619
TI  - Ultrasonic study on binary liquid mixtures between some bromoalkanes and
      hydrocarbons.
AB  - Densities and ultrasound velocities for the binary mixtures of 1
      bromobutane+benzene and 1,4-dimethylbenzene and of 1-bromopentane+cyclohexane and
      benzene have been measured at 308.15 K. Adiabatic compressibilities (beta(ad)),
      and Wada's constants (W) have also been evaluated as a function of composition.
      The ultrasound velocities decrease, attains a minimum and then increase with
      increase in mole fractions of hydrocarbons in the binary mixtures except in the
      case of 1-bromopentane+benzene binary mixtures where the variation is just the
      reverse. Dependence of adiabatic compressibilities with mole fractions of
      hydrocarbons is sigmoid. The non-ideal behaviour of the systems studied is
      explained on the basis of dipole-induced dipole interactions.

PMID- 15975620
TI  - Scrambling of the amino acids within the transmembrane domain of Vpu results in a
      simian-human immunodeficiency virus (SHIVTM) that is less pathogenic for pig
      tailed macaques.
AB  - Previous studies have shown that the transmembrane (TM) domain of the subtype B
      Vpu enhances virion release from cells and some studies have shown that this
      domain may form an oligomeric structure with properties of an ion channel. To
      date, no studies have been performed to assess the role of this domain in virus
      pathogenesis in a macaque model of disease. Using a pathogenic molecular clone of
      simian human immunodeficiency virus (SHIVKU-1bMC33), we have generated a novel
      virus in which the transmembrane domain of the Vpu protein was scrambled but
      maintained hydrophobic in nature (SHIVTM), which presumably would disrupt any ion
      channel TM properties of this protein. Vectors expressing the Vpu as a fusion
      protein with the enhanced green fluorescent protein (VpuTMEGFP) indicate that it
      was transported to the same intracellular compartment as the unmodified Vpu
      protein but did not down-regulate cell surface expression of CD4. To assess the
      pathogenicity of SHIVTM, three pig-tailed macaques were inoculated with the
      SHIVTM and monitored for 6-8 months for CD4+ T cell levels, viral loads and the
      stability of the sequence of the vpu gene. Our results indicated that unlike the
      parental SHIVKU-1bMC33, inoculation of macaques with SHIVTM did not cause a
      severe CD4+ T cell loss over the course of their infections. Sequence analysis of
      the vpu gene analyzed from sequential PBMC samples derived from macaques revealed
      that the scrambled TM was stable during the course of infection. At necropsy,
      examination of tissues revealed low viral loads and none of the pathology
      commonly observed in lymphoid and non-lymphoid tissues following inoculation with
      the pathogenic parental SHIVKU-1bMC33 virus. Thus, these results show for the
      first time that the TM domain of Vpu contributes to the pathogenicity of SHIVKU
      1bMC33 in pig-tailed macaques.

PMID- 15975621
TI  - Complete genomic sequence of the temperate bacteriophage PhiAT3 isolated from
      Lactobacillus casei ATCC 393.
AB  - The complete genomic sequence of a temperate bacteriophage PhiAT3 isolated from
      Lactobacillus (Lb.) casei ATCC 393 is reported. The phage consists of a linear
      DNA genome of 39,166 bp, an isometric head of 53 nm in diameter, and a flexible,
      noncontractile tail of approximately 200 nm in length. The number of potential
      open reading frames on the phage genome is 53. There are 15 unpaired nucleotides
      at both 5' ends of the PhiAT3 genome, indicating that the phage uses a cos-site
      for DNA packaging. The PhiAT3 genome was grouped into five distinct functional
      clusters: DNA packaging, morphogenesis, lysis, lysogenic/lytic switch, and
      replication. The amino acid sequences at the NH2-termini of some major proteins
      were determined. An in vivo integration assay for the PhiAT3 integrase (Int)
      protein in several lactobacilli was conducted by constructing an integration
      vector including PhiAT3 int and the attP (int-attP) region. It was found that
      PhiAT3 integrated at the tRNAArg gene locus of Lactobacillus rhamnosus HN 001,
      similar to that observed in its native host, Lb. casei ATCC 393.

PMID- 15975622
TI  - Coupling enhanced water solubilization with cyclodextrin to indirect
      electrochemical treatment for pentachlorophenol contaminated soil remediation.
AB  - This study undertakes to examine, at laboratory scale, the technical feasibility,
      mechanisms and performances provided by coupling the enhanced flushing abilities
      of cyclodextrin solutions for pentachlorophenol (PCP) removal from contaminated
      soil with indirect electrochemical treatment for the final disposal of soil
      extract solutions containing high PCP loads (0.77mmolL(-1)). The hydroxypropyl
      beta-cyclodextrin (HPCD) solution increased the aqueous concentration of PCP in
      soil extract effluents to as much as 3.5 times the concentrations obtained during
      the water flush of the soil. PCP was treated with electrochemically generated
      Fenton's reagent in an aqueous medium. The increase in PCP water solubility in
      the presence of HPCD is balanced by the corresponding decrease in PCP degradation
      rate under indirect electrochemical treatment. This is due to the high carbon
      content (HPCD and dissolved natural organic matter) in the soil extract
      solutions, which compete for the non-selective hydroxyl radical reaction to PCP.
      However, our results indicate that HPCD has a beneficial effect on the
      degradation rates of PCP. This relative improvement in PCP degradation could be
      explained by the formation of the ternary complex (PCP-cyclodextrin-iron) which
      may direct hydroxyl reaction to PCP and which would, in any case, justify the use
      of a Fenton -like process for the final treatment of soil extract solutions.
      Total disappearance of PCP and 90% abatement of the chemical oxygen demand were
      achieved within an 11h electrolysis treatment time. Elucidation of the PCP
      degradation pathway indicates that after successive PCP hydroxylations, oxidative
      opening of the PCP aromatic ring quickly occurred, leading to small unstable non
      chlorinated or partially chlorinated short chain carboxylic acids, such as
      monochloroacetic and dichloromaleic acid. Determination of the concentration of
      these acids shows that indirect electrochemical treatment leads to oxalic acid
      accumulation in aqueous solutions treated. A decrease in toxicity was observed at
      the end of the treatment time.

PMID- 15975623
TI  - Synthesis of 4-(1-oxo-isoindoline) and 4-(5,6-dimethoxy-1-oxo-isoindoline)
      substituted phenoxypropanolamines and their beta1-, beta2-adrenergic receptor
      binding studies.
AB  - Phenoxypropanolamines with 1-oxo-isoindoline and 5,6-dimethoxy-1-oxo-isoindoline
      groups at the para position were synthesized. beta1, beta2-Adrenergic receptor
      binding affinities for the synthesized compounds were tested and compared with
      propranolol and atenolol. It was found that the incorporation of para-amidic
      functionality within the 1-oxo-isoindoline ring and 5,6-dimethoxy-1-oxo
      isoindoline ring system led to a high degree of cardioselectivity in the
      phenoxypropanolamines. Two of the compounds and possessed beta1-adrenergic
      receptor affinity comparable with that of atenolol and both showed a better
      cardioselectivity than atenolol. Both and are undergoing further pharmacological
      evaluation.

PMID- 15975624
TI  - Catalytic amination and dechlorination of para-nitrochlorobenzene (p-NCB) in
      water over palladium-iron bimetallic catalyst.
AB  - Chemical treatment of para-nitrochlorobenzene (p-NCB) by palladium/iron (Pd/Fe)
      bimetallic particles represents one of the latest innovative technologies for the
      remediation of contaminated soil and groundwater. The amination and
      dechlorination reaction is believed to take place predominantly on the surface
      site of the Pd/Fe catalysts. The p-NCB was first transformed to p-chloroaniline
      (p-CAN) then quickly reduced to aniline. 100% of p-NCB was removed in 30 min when
      bimetallic Pd/Fe particles with 0.03% Pd at the Pd/Fe mass concentration of 3g 75
      ml(-1) were used. The p-NCB removal efficiency and the subsequent dechlorination
      rate increased with the increase of bulk loading of palladium and Pd/Fe. As
      expected, p-NCB removal efficiency increased with temperature as well. In
      particular, the removal efficiency of p-NCB was measured to be 67%, 79%, 80%, 90%
      and 100% for reaction temperature 20, 25, 30, 35 and 40 degrees C, respectively.
      Our results show that no other intermediates were generated besides Cl(-), p-CAN
      and aniline during the catalytic amination and dechlorination of p-NCB.

PMID- 15975625
TI  - Kinetics of low frequency sonodegradation of linear alkylbenzene sulfonate
      solutions.
AB  - The decomposition of sodium dodecylbenzene sulfonate (SDBS) in water by means of
      ultrasound irradiation at 20kHz was investigated. Experiments were conducted at
      surfactant concentrations of 175, 260 and 350 mg l(-1), liquid volumes of 120,
      170 and 220 ml, temperatures of 20, 30 and 45 degrees C and applied power of 40,
      80 and 125 W. The extent of degradation was followed monitoring substrate and
      organic carbon concentrations, while hydrogen peroxide concentration was also
      measured; the latter is a product of water sonolysis due to hydroxyl radical
      recombination. 80% SDBS conversion was achieved after 120 min of sonication at
      125 W and 30 degrees C; nonetheless, SDBS and its degradation intermediates
      proved difficult to oxidise as only about 20-25% of the initial carbon content
      was transformed to carbon dioxide. At the initial stages of the reaction,
      degradation rate appears to be only weakly dependent on the substrate
      concentration with the rate increasing from 3.1 to 4 mg l(-1)min(-1) with
      increasing concentration from 175 to 350 mg l(-1). Degradation appears to occur
      at the bubble-liquid interface through hydroxyl radical-mediated reactions whose
      role was established by performing experiments in the presence of radical
      scavengers, namely potassium bromide and sodium benzoate. Degradation rates
      increased with increasing power and decreasing temperature and volume.

PMID- 15975626
TI  - Stochastic model to forecast ground-level ozone concentration at urban and rural
      areas.
AB  - Stochastic models that estimate the ground-level ozone concentrations in air at
      an urban and rural sampling points in South-eastern Spain have been developed.
      Studies of temporal series of data, spectral analyses of temporal series and
      ARIMA models have been used. The ARIMA model (1,0,0) x (1,0,1)24 satisfactorily
      predicts hourly ozone concentrations in the urban area. The ARIMA (2,1,1) x
      (0,1,1)24 has been developed for the rural area. In both sampling points,
      predictions of hourly ozone concentrations agree reasonably well with measured
      values. However, the prediction of hourly ozone concentrations in the rural point
      appears to be better than that of the urban point. The performance of ARIMA
      models suggests that this kind of modelling can be suitable for ozone
      concentrations forecasting.

PMID- 15975627
TI  - Gas- and particulate-phase specific tracer and toxic organic compounds in
      environmental tobacco smoke.
AB  - Cigarette smoke constituents are worthy of concern and characterized as
      carcinogens. Different experiment conditions may affect the environmental tobacco
      smoke (ETS) constituents. A study was undertaken in a 75.5-m3 spare office to
      evaluate ETS constituents in a real environment. Thirty-four volatile organic
      compounds (VOCs) including three ETS tracers: nicotine, 2,5-dimethylfuran and 3
      ethenylpyridine (3-EP), 19 carbonyl compounds, 54 semi-volatile compounds (24
      polycyclic aromatic hydrocarbons (PAHs) and 30 alkanes) as well as CO and total
      particulate matter (TPM) from 15 leading commercial brands were determined. ETS
      constituents did not increase with increasing cigarette tar. ETS tracers nicotine
      and 3-EP were affected greatly due to more sorption and surface reactions in real
      world compared to other studies conducted in chamber, which resulted in 2-5 times
      lower. Benzene, toluene, ethylbenzene, xylenes, acrolein, 2-butanone and the high
      molecular weight compounds exhibited little affect. Pearson correlation analyses
      show that gas-phase and particulate-phase ETS tracers did not show significant
      correlation, but within each homologue many of compounds correlated
      significantly. Indole and cholesta-3,5-diene were also detected in ETS. These
      results may be useful in efforts to better understand the health effect of ETS
      exposure and source apportionment.

PMID- 15975628
TI  - Formation of toxic chemicals including dioxin-related compounds by combustion
      from a small home waste incinerator.
AB  - We investigated combustion in a small home waste incinerator and analyzed both
      flue gas and residual ash for formation of the dioxin-related compounds
      polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar
      polychlorinated biphenyls and their precursors polychlorinated benzenes,
      polychlorinated phenols, polychlorinated diphenyl ethers, and polychlorinated
      biphenyls. Particularly, we investigated the effect of the incinerated material's
      composition on both the congener ratios of released compounds and the total
      concentration of all congeners of each compound. Eight different samples were
      prepared for incineration with four samples consist entirely paper, dead leaves,
      natural wood, or building materials. The remaining four samples contained mostly
      paper, but also other components such as fiber, non-chlorine-containing plastics,
      chlorine-containing plastics, and copper electric wire. The presence of non
      chlorine-containing plastic in combustion samples did not increase overall dioxin
      or dioxin-precursor emissions. In contrast, chlorine-containing plastic resulted
      in a several-fold increase in total polychlorinated dioxins released, in both
      flue gas and residual ash. Copper wire resulted in a further several-fold
      increase in total polychlorinated dioxins and dioxin precursors released, with
      one exception: the addition of chlorine-containing plastic resulted in a many
      fold increase in polychlorinated biphenyls, but only a modest further increase (
      approximately 52%) with the further addition of copper. Homologue ratios tended
      toward higher-chlorine compounds as chlorine-containing plastic and Cu were
      added, but the results were far from uniform. Our results show that toxic dioxin
      release from small home waste incinerators must be considered significant,
      especially if even small amounts of chlorine-containing plastics or copper are
      burned.

PMID- 15975629
TI  - Isotope evidence for the intensive use of marine foods by Late Upper Palaeolithic
      humans.
AB  - We report here on direct evidence for the intensive consumption of marine foods
      by anatomically modern humans at approximately 12,000 years ago. We undertook
      isotopic analysis of bone collagen from three humans, dating to the late
      Palaeolithic, from the site of Kendrick's Cave in North Wales, UK. The isotopic
      measurements of their bone collagen indicated that ca. 30% of their dietary
      protein was from marine sources, which we interpret as likely being high trophic
      level marine organisms such as marine mammals. This indicates that towards the
      end of the Pleistocene modern humans were pursuing a hunting strategy that
      incorporated both marine and terrestrial mammals. This is the first occurrence of
      the intensive use of marine resources, specifically marine mammals, that becomes
      even more pronounced in the subsequent Mesolithic period.

PMID- 15975630
TI  - Taphonomic bias, taxonomic bias and historical non-equivalence of faunal
      structure in early hominin localities.
AB  - Environmental interpretation of fossil assemblages requires an accurate
      reconstruction of the community from which the assemblage was derived, which in
      turn depends on the quality of a comparative model usually based on the study of
      modern equivalents. The degree of inaccuracy introduced by taphonomic and other
      types of bias is often difficult to assess and the suitability of comparative
      models has rarely been addressed in this light. Here we apply a recently
      developed method to assess the bias present in a range of key hominin bearing
      localities from the Neogene of East and South Africa. The ecological structure of
      several of the investigated faunas can be shown to depart substantially from that
      of a comprehensive range of modern comparative faunas. Bias, where present,
      affects primarily the small mammals, which tend to be under-represented, and the
      large primary consumers, which tend to be over-represented. This has potentially
      significant implications for past and future palaeoecological reconstruction of
      these localities as numerous methods that are currently in use rely extensively
      on either the small mammals or the large primary consumers, and in particular the
      bovids. Understanding the nature of the bias, when present, will go some way
      towards improving the quality of environmental reconstructions.

PMID- 15975631
TI  - Electromagnetic hypersensitivity (EHS) and subjective health complaints
      associated with electromagnetic fields of mobile phone communication--a
      literature review published between 2000 and 2004.
AB  - Literature published between 2000 to 2004 concerning electromagnetic fields (EMF)
      of mobile communication and electromagnetic hypersensitivity (EHS) or unspecific
      symptoms of ill health, respectively, is reviewed. Basically, literature from
      established databases was systematically searched for. For each study, the design
      and quality were evaluated by means of a criteria list in order to judge evidence
      for causality of exposures on effects. Finally, 13 studies of sufficient quality
      were considered for this review. In only one provocation study, individuals with
      self-reported electromagnetic hypersensitivity were exposed to EMF. Their
      perception of field status was no better than would have been expected by chance.
      Results of five randomised cross-over studies on impaired well-being due to
      mobile phone exposure were contradictory. Even though these studies would allow
      more reliable exposure assessment, they are limited due to short exposure period
      and the small study size. No firm conclusion could be drawn from a few
      observational epidemiological studies finding a positive association between
      exposure and unspecific symptoms of ill health due to methodological limitations.
      Causality of exposure and effect was not derivable from these cross-sectional
      studies as field status and health complaints were assessed at the same time. In
      addition, exposure assessment has not been validated. In conclusion, based on the
      limited studies available, there is no valid evidence for an association between
      impaired well-being and exposure to mobile phone radiation presently. However,
      the limited quantity and quality of research in this area do not allow to exclude
      long-term health effects definitely.

PMID- 15975632
TI  - Blending foundry sands with soil: Effect on dehydrogenase activity.
AB  - Each year U.S. foundries landfill several million tons of sand that can no longer
      be used to make metalcasting molds and cores. A possible use for these materials
      is as an ingredient in manufactured soils; however, potentially harmful metals
      and resin binders (used to make cores) may adversely impact the soil microbial
      community. In this study, the dehydrogenase activity (DHA) of soil amended with
      molding sand (clay-coated sand known as "green sand") or core sands at 10%, 30%,
      and 50% (dry wt.) was determined. The green sands were obtained from iron,
      aluminum, and brass foundries; the core sands were made with phenol-formaldehyde
      or furfuryl alcohol based resins. Overall, incremental additions of these sands
      resulted in a decrease in the DHA which lasted throughout the 12-week
      experimental period. A brass green sand, which contained high concentrations of
      Cu, Pb, and Zn, severely impacted the DHA. By week 12 no DHA was detected in the
      30% and 50% treatments. In contrast, the DHA in soil amended with an aluminum
      green sand was 2.1 times higher (all blending ratios), on average, at week 4 and
      1.4 times greater (30% and 50% treatments only) than the controls by week 12. In
      core sand-amended soil, the DHA results were similar to soils amended with
      aluminum and iron green sands. Increased activity in some treatments may be a
      result of the soil microorganisms utilizing the core resins as a carbon source.
      The DHA assay is a sensitive indicator of environmental stress caused by foundry
      sand constituents and may be useful to assess which foundry sands are suitable
      for beneficial use in the environment.

PMID- 15975633
TI  - Development of a database system for the calculation of indicators of
      environmental pressure caused by transport.
AB  - The scope of this paper is to summarise a methodology developed for TRENDS
      (TRansport and ENvironment Database System-TRENDS). The main objective of TRENDS
      was the calculation of environmental pressure indicators caused by transport. The
      environmental pressures considered are associated with air emissions from the
      four main transport modes, i.e. road, rail, ships and air. In order to determine
      these indicators a system for calculating a range of environmental pressures due
      to transport was developed within a PC-based MS Access environment. Emphasis is
      given on the latest features incorporated in the model and their applications.
      One of the recently developed features of the software provides an option for
      simple scenario analysis including vehicle dynamics (such as turnover and
      evolution) for all EU15 member states. This feature is called the Transport
      Activity Balance module (TAB) and enables the production of collective results
      for all transport modes as well as a comparative assessment of air emissions
      produced by the various modes. Traffic activity and emission data obtained
      according to a basic (reference) scenario are displayed for the time period 1970
      2020. In addition, a detailed assessment of the results produced by TRENDS was
      conducted by means of comparison with data found in the literature. Finally,
      vehicle emissions produced by the model for the EU15 member states were spatially
      disaggregated for the base year, 1995 and GIS maps were generated. Examples of
      these maps are displayed in this document, for the various modes of transport
      considered in the study.

PMID- 15975634
TI  - Levels of toxaphene congeners in white whales (Delphinapterus leucas) from
      Svalbard, Norway.
AB  - This study reports concentrations of three pesticide toxaphene congeners (CHBs;
      CHB-26, -50 and -62) from the blubber of ten adult, male white whales
      (Delphinapterus leucas) from Svalbard, Norway. The CHB congeners that occurred at
      the highest levels in the blubber of the white whales were, as expected, CHB-26
      (4636+/-1992 (SD) ng/g l.w.) and CHB-50 (6579+/-2214 ng/g l.w.); CHB-62 (232+/
      231 ng/g l.w.) was also present, but at much lower concentrations. The mean level
      of the sum of the three CHBs (SigmaCHBs = 11,447+/-4208 ng/g l.w.) in this study
      is more than twice the mean concentrations of the well-known organochlorine (OC)
      pollutants SigmaDDTs (sum of pp'-DDT, pp'-DDE, pp'-DDD) and SigmaPCBs (sum of 27
      PCB congeners) previously reported from the same individual white whales. The
      concentrations of CHBs in white whales from Svalbard are at the high end of the
      range for concentrations of these compounds compared to other Arctic white whale
      populations. Additionally, the contribution of CHBs to the overall OC burden is
      larger in white whales from Svalbard compared with their counterparts from other
      areas in the Arctic. Male white whales from Svalbard have several orders of
      magnitude higher concentrations of SigmaCHBs compared to seals and polar bears
      (Ursus maritimus) from the same area. The high levels of CHBs in these whales,
      and their dominance in the OC pattern, suggests that white whales in Svalbard are
      exposed to high levels of this group of contaminants. Further studies are needed
      to investigate possible effects of CHBs and other OC contaminants on the white
      whale population in Svalbard.

PMID- 15975635
TI  - Lead associated caries development in children living in a lead contaminated
      area, Thailand.
AB  - In an observational cross-sectional design, a sample of 292 children aged 6-11
      years from two primary schools around a shipyard area, known to be an area
      contaminated with lead (from the industry), were examined to verify the
      cariogenicity of lead. The number of decayed and filled surfaces on deciduous
      teeth (dfs), and the number of decayed, missing, and filled surfaces on permanent
      teeth (DMFS), the salivary flow rate, pH, buffer capacity, oral hygiene,
      Lactobacillus spp. and mutans streptococci counts were recorded. The mean (range)
      of DMFS and dfs were respectively 1.3 (range 0-17) and 13.2 (range 0-45); and the
      geometric mean blood lead level (PbB) and SD were 7.2 and 1.5 microg/dl. The
      level of dfs, but not DMFS correlated with the blood lead level (R(s)=0.25,
      p=0.00 / R(s)=0.09, p=0.14). The odds ratio for DMFS>or=1 and dfs>5 for a
      doubling of PbB after adjusting for other factors were 1.28 (95%CI, 0.81-2.04; p
      value=0.35) and 2.39 (95%CI, 1.36-4.20; p value=0.004), respectively. The
      cariogenicity of lead is evident in deciduous teeth but not in permanent teeth
      for this age group.

PMID- 15975636
TI  - Bleeding in patients with renal insufficiency: a practical guide to clinical
      management.

PMID- 15975637
TI  - Serious workings of the funny current.
AB  - Since its first description in 1979 (Brown et al., 1979. Nature 280, 235-236),
      extensive work on the I(f) current has amply demonstrated its role in the
      generation and neurotransmitter-induced modulation of pacemaker activity in heart
      (DiFrancesco, 1993. Annual Review of Physiology 55, 455-472). At pacemaker
      voltages, I(f) is an inward current activated by negative voltage and by
      intracellular cAMP. Moderate beta-receptor stimulation accelerates, and vagal
      stimulation slows, cardiac rate by increasing and decreasing, respectively, I(f)
      at diastolic potentials via changes in cAMP level. Cloning of four isoforms of
      hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channels in the late
      1990s has shown their correlation to native f-channels. Comparison of the
      properties of native pacemaker channels with those of HCN channels has provided
      information concerning the composition and molecular features of native channels
      in different cardiac regions. The relevance of I(f) to pacemaker generation and
      modulation makes f-channels a natural target of drugs aiming to control
      pharmacologically heart rate. Agents selectively reducing heart rate have been
      developed which act by specific inhibition of I(f), such as ivabradine; these
      drugs have a high potential for treatment of diseases where heart rate reduction
      is beneficial, such as angina and heart failure. Knowledge of the molecular
      properties of HCN clones will help the development of drugs specifically
      interacting with cardiac, rather than neuronal pacemaker channels. Devices able
      to replace electronic pacemakers and based on the delivery of a cellular source
      of pacemaker channels to non-pacing tissue (biological pacemakers) are likely to
      be developed in the near future for use in therapies for diseases of heart
      rhythm.

PMID- 15975639
TI  - Invasive inflammatory pseudotumor of uterine cervix: a case report.
AB  - BACKGROUND: Inflammatory pseudotumor (IPT) of the cervix uteri has been reported
      in only one patient. Here, we present a case of cervical IPT with bilateral
      parametrial involvement causing hydroureteronephrosis. CASE: A 48-year-old,
      gravida 2, para 1, woman was referred for evaluation of lower abdominal pain and
      right-sided hydroureteronephrosis. On speculum and colposcopic examinations, the
      cervix appeared normal. Computed tomography scan revealed a 5 cm x 4 cm mass in
      the cervix invading both parametria. At laparotomy, the cervix was globally
      enlarged and both parametria were infiltrated by a tumor of rubbery consistency.
      After freeing both ureters, the cervix was removed with bilateral parametria and
      2-cm vaginal cuff. Histologically, the tumor was characterized by proliferation
      of fibroblast-like spindle cells and diffuse infiltration of plasma cells and
      lymphocytes. Immunohistochemical staining showed that the lymphocytes were
      polyclonal. Immunostaining for smooth muscle actin was negative. The tumor was
      thus identified as inflammatory pseudotumor. Cervical stroma, bilateral
      parametria, and subepithelial tissues of the vagina were involved with tumor.
      However, invasion was not identified in the epithelia of the cervix and vagina or
      surgical margins of the resected specimen. Postoperative course was uneventful.
      There is no evidence of recurrent disease 8 months following surgery. CONCLUSION:
      The case we present is the second reported case of cervical IPT. It is unique in
      showing locally aggressive behavior. Surgical resection appears to be the
      treatment of choice for IPT.

PMID- 15975638
TI  - Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in
      endometrial carcinoma: a Gynecologic Oncology Group Study.
AB  - OBJECTIVE: In patients with disseminated endometrial carcinoma, liposomal
      doxorubicin has possible advantages over doxorubicin which has proven single
      agent activity but well known cardiac toxicity. Before replacing doxorubicin in
      clinical trials, the Gynecologic Oncology Group (GOG) decided to conduct a phase
      II clinical trial of liposomal doxorubicin (Ortho Biotech Products L. P.,
      Raritan, NJ) in first-line therapy of patients with disseminated endometrial
      carcinoma. METHODS: Patients with initial histologic confirmation of endometrial
      carcinoma presenting with disseminated or recurrent cancer who had not previously
      received cytotoxic drugs were considered for participation in this clinical
      trial. Eligible patients had measurable disease, GOG performance status 0-2, and
      adequate bone marrow, renal, and hepatic function according to standard criteria.
      Liposomal doxorubicin 40 mg/m(2) was given by intravenous injection on an every 4
      week cycle until toxicity or progression. Patients who remained free from tumor
      progression or intolerable toxicity received at least one to a maximum of 20
      cycles of liposomal doxorubicin. RESULTS: Fifty-six patients were registered, of
      whom three were determined ineligible (prior malignancy = 2, inadequate pathology
      material = 1). One patient never received therapy, leaving 52 evaluable patients.
      Two patients (3.8%) achieved a complete response, four (7.7%) exhibited a partial
      response, and 31 (59.7%) had stable disease. The most common adverse events were
      constitutional (32/52), anemia (28/52), pain (27/52), dermatologic (25/52), and
      cardiovascular (12/52). CONCLUSIONS: In this trial, liposomal doxorubicin had a
      response rate of 11.5% in first-line treatment of disseminated endometrial
      carcinoma when given at 40 mg/m(2) every 4 weeks. In view of the associated skin
      toxicity at this dose, liposomal doxorubicin does not appear to be a suitable
      replacement for the more active doxorubicin for therapy of endometrial carcinoma.

PMID- 15975640
TI  - Osteomalacia due to chemotherapy-induced Fanconi syndrome in an adult patient.
AB  - BACKGROUND: Chemotherapy-induced Fanconi syndrome is a dangerous condition that
      could lead to severe electrolyte disturbances and rarely to osteomalacia. CASE: A
      patient treated with ifosfamide for a metastatic cervix squamous-cell carcinoma
      was admitted for diffuse, symmetric bilateral pain in bones and articulations.
      The diagnosis work-up revealed that she suffered from osteomalacia due to a
      chemotherapy-induced Fanconi syndrome. The patient recovered completely with oral
      calcitriol supplements. CONCLUSIONS: This very rare chemotherapy-complication
      suggests that detection of potential tubular dysfunction, by regular serum
      electrolyte monitoring of patients receiving ifosfamide, may be a reasonable
      approach to diagnose early chemotherapy-induced Fanconi syndrome, even in adults.

PMID- 15975641
TI  - Phase II evaluation of topotecan in carcinosarcoma of the uterus: a Gynecologic
      Oncology Group study.
AB  - OBJECTIVES: To estimate the antitumor activity of topotecan in patients with
      persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the
      uterus and to determine the nature and degree of toxicity of topotecan in this
      cohort of patients. MATERIALS AND METHODS: Eligible patients had measurable
      advanced or recurrent carcinosarcoma of the uterus. Topotecan at a target dose of
      1.5 mg/m(2) was administered IV daily for 5 days, every 3 weeks, until
      progression of disease or adverse affects prohibited further therapy. RESULTS:
      Twenty-seven member institutions entered 51 patients. Of the patients entered, 48
      were eligible. Patient characteristics included a median age of 65, with 33%
      having prior radiation and 92% having prior chemotherapy. Twenty-six patients
      (54%) had a performance status (PS) of 0, 18 (38%) had a PS of 1, and four (8%)
      had a PS of 2. Patients received from 1 to 21 (with a median of 2) courses of
      treatment. The most frequently observed grade 4 toxicities were neutropenia seen
      in 35 (73%) patients, leukopenia in 14 (29%), and thrombocytopenia in 10 (21%).
      Three (6%) patients developed neutropenic sepsis and died shortly after their
      first treatment cycle. There were five (10%) complete responses; 13 (27%)
      patients maintained stable disease, 26 (54%) experienced increasing disease, and
      reassessment did not occur in four (8%). CONCLUSION: Topotecan at this dose and
      schedule does not appear to have major activity in patients with advanced or
      recurrent uterine carcinosarcoma previously treated with chemotherapy.

PMID- 15975642
TI  - Outcomes of Stage I/II vulvar cancer patients after negative superficial inguinal
      lymphadenectomy.
AB  - OBJECTIVES: To investigate the patterns of recurrence associated with superficial
      inguinal lymphadenectomy (SupIL) and vulvectomy for patients with Stage I/II
      vulvar cancer. METHODS: A retrospective chart review identified patients from
      1990-2001 with Stage I/II vulvar cancer that underwent SupIL and vulvectomy.
      Survival was analyzed using the Kaplan-Meier method with Fisher Exact and Chi
      square tests for comparisons between groups. RESULTS: 65 patients with Stage I/II
      vulvar cancer with a pathologically negative SupIL were identified (30 Stage I,
      35 Stage II). Three patients recurred in the inguinal region, (4.6%) and 11
      patients (16.9%) recurred on the vulva. Two of the 11 patients died of disease,
      six patients are alive without evidence of disease after additional therapy. Five
      year disease-free survival and overall survival were 66% and 97%, respectively.
      Risk of recurrence was not associated with smoking status, stage, or margin
      status. CONCLUSIONS: SupIL and vulvectomy for Stage I/II vulvar cancer have a low
      recurrence rate in the inguinal region when nodes are negative. The local
      recurrence rate (17%) is acceptable, and overall survival is good using this
      conservative approach.

PMID- 15975643
TI  - Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer:
      updated results and long-term survival.
AB  - OBJECTIVE: The combination of GEM/PLD has been tested for its efficacy on
      survival of recurrent ovarian cancer patients. METHODS: This is a multicenter
      phase II study of GEM/PLD regimen in recurrent ovarian cancer patients previously
      treated with at least one platinum/paclitaxel regimen, and with evidence of
      measurable disease. PLD, 30 mg m(-2), was administered on day 1 followed by GEM,
      1000 mg m(-2), on days 1 and 8, every 21 days. RESULTS: 106 patients were
      available for response evaluation. 9 complete responses (8.5%) and 27 partial
      responses (25.5%) have been registered. 36 patients (34.0%) experienced
      stabilization of disease, while 34 (32.1%) cases progressed during treatment. OS
      was significantly shorter in platinum-resistant (median OS = 50 weeks) than in
      platinum-sensitive patients (median OS = 92 weeks) (P value = 0.0016). In the
      group of platinum-sensitive patients, cases responsive to GEM/PLD combination
      showed a better OS with respect to patients unresponsive to GEM/PLD (median OS =
      120 weeks versus median OS = 60 weeks, P value = 0.019). The same trend was
      observed in platinum-resistant patients. Grade 4 hematological toxicity affected
      20 patients (18%). Grade 3 palmar-plantar erythrodysesthesia (PPE) was registered
      in 16 patients (14.4%). Grades 3 and 4 mucositis was documented in 16 (14.4%) and
      2 (1.8%) patients, respectively. CONCLUSIONS: GEM/PLD combination represents a
      valid approach in recurrent ovarian cancer patients. The hematological toxicity
      was easily managed, and the incidence and severity of PPE was low.

PMID- 15975644
TI  - Breastfeeding and the risk of epithelial ovarian cancer in an Italian population.
AB  - OBJECTIVES: Breastfeeding has been inversely related to the risk of ovarian
      cancer, but results from published studies are inconsistent. In order to provide
      further information, we analyzed data from a large case-control study conducted
      in four Italian areas. METHODS: Cases were 1031 women with epithelial ovarian
      cancer. Controls were 2411 women admitted to the same network of hospitals for a
      wide spectrum of acute non-neoplastic conditions, unrelated to known risk factors
      for ovarian cancer. RESULTS: There were inverse trends in risk with increasing
      duration of breastfeeding and number of children breastfed, but when parity and
      several other potential confounding factors were taken into account, no residual
      association was evident (odds ratio = 1.21 for 17 or more months of breastfeeding
      and 0.90 for those who had breastfed 4 or more children, as compared to women who
      had never breastfed). CONCLUSIONS: This study showed an inverse relation between
      breastfeeding and ovarian cancer risk, which however was accounted for by parity.
      The analyses by histologic subtypes suggested that a role of breastfeeding would
      be larger for serous neoplasms in the absence, however, of significant
      heterogeneity.

PMID- 15975645
TI  - Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of
      human cervical cancer.
AB  - OBJECTIVE: To determine the impact of thalidomide and angiostatin on tumor
      growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer.
      METHODS: Human umbilical endothelial cells were treated with angiostatin or
      thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human
      cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude
      mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or
      thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and
      immunohistochemical analysis of tumors was used to determine degree of
      angiogenesis. TUNEL assay was used to assess apoptosis. RESULTS: Angiostatin
      inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct
      effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor
      growth by about 55%. We found no additive or synergistic effect when the two
      agents were combined. Both agents inhibited angiogenesis and induced apoptosis
      when compared to tumors from control animals. CONCLUSIONS: Angiostatin and
      thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this
      xenograft model of cervical cancer.

PMID- 15975646
TI  - Short-term progestin treatments prevent estrous induction by a GnRH agonist
      implant in anestrous bitches.
AB  - The objective of this study was to test the efficacy and safety of a short-term
      progestin treatment administered at two different times to prevent estrous
      induction in response to the administration of an implant releasing the GnRH
      agonist, deslorelin acetate (DA), in anestrous bitches. Interestrous intervals
      (IEI) observed prior to and post DA were compared. Forty-two anestrous bitches,
      with previous IEI history, were randomly allocated to one of the following
      treatments: PL: placebo sc (n = 12); MA: megestrol acetate 2mg/kg po for 8 days
      (n = 4); DA: 10mg sc (n = 8); MA&DA-1: MA beginning the day before DA (n = 8);
      and MA&DA-4: MA beginning 4 days before DA (n = 10). The dose of MA was identical
      for each treatment. All bitches were examined daily for 1 month and then every 3
      months until the next spontaneous post-treatment estrous cycle. Post-GnRH estrous
      response occurred in 0, 0, 100, 50, and 10% of the PL, MA, DA, MA&DA-1, MA&DA-4,
      groups, respectively (<0.01). There was an interaction between the treatment and
      period for the duration of the IEI (< 0.01). Changes in IEI were different among
      treatments (p<0.01); the three DA-treated groups (147.5% +/- 10.3, 161.3% +/-
      14.1, 148.6% +/- 19.2) differed from both the MA (12.9% +/- 17.6) and PL (8.1% +/
      7.8), but not among themselves. It is concluded that an 8 days megestrol
      protocol and DA on Day 4 was better than DA on Day 1 to prevent estrous response
      in anestrous bitches and that both protocols significantly increased the IEI.

PMID- 15975647
TI  - Diagnosis and repair of negative polarity constructions in the light of symbolic
      resonance analysis.
AB  - In a post hoc analysis, we investigate differences in event-related potentials of
      two studies (Drenhaus et al., 2004, Drenhaus et al., to appear, Saddy et al.,
      2004a and Saddy et al., 2004b) by using the symbolic resonance analysis (Beim
      Graben & Kurths, 2003). The studies under discussion, examined the failure to
      license a negative polarity item (NPI) in German: Saddy et al. (2004a) reported
      an N400 component when the NPI was not accurately licensed by negation; Drenhaus
      et al., 2004 and Drenhaus et al., to appear considered additionally the influence
      of constituency of the licensor in NPI constructions. A biphasic N400-P600
      response was found for the two induced violations (the lack of licensor and the
      inaccessibility of negation in a relative clause). The symbolic resonance
      analysis (SRA) revealed an effect in the P600 time window for the data in Saddy
      et al., which was not found by using the averaging technique. The SRA of the ERPs
      in Drenhaus et al., showed that the P600 components are distinguishable
      concerning the amplitude and latency. It was smaller and earlier in the condition
      where the licensor is inaccessible, compared to the condition without negation in
      the string. Our findings suggest that the failure in licensing NPIs is not
      exclusively related to semantic integration costs (N400). The elicited P600
      components reflect differences in syntactic processing. Our results confirm and
      replicate the effects of the traditional voltage average analysis and show that
      the SRA is a useful tool to reveal and pull apart ERP differences which are not
      evident using the traditional voltage average analysis.

PMID- 15975648
TI  - Physicochemical model of alginate-poly-L-lysine microcapsules defined at the
      micrometric/nanometric scale using ATR-FTIR, XPS, and ToF-SIMS.
AB  - Alginate-poly-L-lysine-alginate (APA) microcapsules are currently being
      investigated as a means to immuno-isolate transplanted cells, but their
      biocompatibility is limited. In this study, we verified the hypothesis that poly
      L-lysine (PLL), which is immunogenic when unbound, is exposed at the APA
      microcapsule surface. To do so, we analysed the microcapsule membrane at the
      micrometric/nanometric scale using attenuated total reflectance Fourier transform
      infrared spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight
      secondary ion mass spectrometry. The results indicate that PLL and alginate
      molecules interact within the membrane. PLL exists in considerable amounts near
      the surface, contributing to the majority of the carbon within the outermost 100
      Angstroms of the membrane. PLL was also detected at the true surface (the
      outermost monolayer) of the microcapsules. The exposure of PLL does not appear to
      result from defects in the outer alginate coating. This physicochemical model of
      APA microcapsules could explain their immunogenicity and will play an important
      role in the optimization of the microcapsule design.

PMID- 15975649
TI  - The bone response of oxidized bioactive and non-bioactive titanium implants.
AB  - A number of experimental and clinical data on so-called oxidized implants have
      reported promising outcomes. However, little is investigated on the role of the
      surface oxide properties and osseointegration mechanism of the oxidized implant.
      Sul [On the Bone Response to Oxidized Titanium Implants: The role of microporous
      structure and chemical composition of the surface oxide in enhanced
      osseointegration (thesis). Goteborg: Department of Biomaterials/Handicap
      Research, University of Goteborg, Sweden; 2002; Biomaterials 2003; 24: 3893-3907]
      recently proposed two action mechanisms of osseointegration of oxidized implants,
      i.e. mechanical interlocking through bone growth in pores/other surface
      irregularities (1) and biochemical bonding (2). The aim of the present study is
      two-fold: (i) investigating the role of the implant surface chemistry on bone
      responses; (ii) investigating the validity of the biochemical bonding theory of
      the oxidized, bioactive bone implants with specific implant surface chemistry.
      Two groups of oxidized implants were prepared using micro arc oxidation process
      and were then inserted in rabbit bone. One group consisted of magnesium ion
      incorporated implants (MgTiO implant), the other consisted of TiO2 stoichiometry
      implants (TiO implant). Surface oxide properties of the implants were
      characterized with various surface analytic techniques. After 6 weeks of follow
      up, the mean peak values of removal torque of Mg implants dominated significantly
      over TiO implants (p < or = 0.0001). Bonding failure generally occurred in the
      bone away from the bone to implant interface for the MgTiO implant and mainly
      occurred at the bone to implant interface for the TiO implant that consisted
      mainly of TiO2 chemistry and significantly rougher surface as compared to the
      MgTiO implant. Between bone and the Mg- incorporated implant surface, ionic
      movements and ion concentrations gradient were detected. The current in vivo
      experimental data may provide positive evidence for the surface chemistry
      mediated biochemical bonding theory of oxidized bioactive implants. However, the
      present study does not rule out potential synergy effects of the oxide thickness,
      micro-porous structure, crystal structure and surface roughness on improvements
      of bone responses to oxidized bioactive implants.

PMID- 15975650
TI  - Inhibition of DLX4 promotes apoptosis in choriocarcinoma cell lines.
AB  - Homeodomain (HDM) proteins encoded by homeobox (HBX) genes represent a large
      family of transcriptional factors that control differentiation and development in
      certain cell types. DLX4 is a member of Distal-less (DLX) family of HBX genes.
      Recent studies have demonstrated that abnormal expression of DLX4 is present in
      several types of human tumors, such as breast cancer, leukemia and colon cancer.
      In the present study, we investigated DLX4 mRNA and protein expression in both
      normal placental tissues and human choriocarcinoma cell lines. Also, using RNA
      interference (RNAi) technique, we knocked down the expression of DLX4 and
      examined apoptosis in JEG-3 cells. Our studies demonstrated that DLX4 RNAi
      inhibited DLX4 mRNA expression and decreased DLX4 protein mass specifically and
      effectively, potentially enhancing apoptosis. Moreover, we examined expression of
      caspase-3 and caspase-8, and found that both caspases were increased after DLX4
      knockdown. However, DLX4 RNAi did not influence Bax expression in JEG-3 cells. In
      conclusion, this study suggests that DLX4 may be involved in the survival of
      human choriocarcinoma cells, which may be mediated by the inhibition of
      apoptosis. The detailed mechanism needs further investigation.

PMID- 15975651
TI  - Differential excitatory responses to oxytocin in sub-divisions of the bed nuclei
      of the stria terminalis.
AB  - The lateral dorsal nucleus of the bed nuclei of the stria terminalis (BST-LD)
      expresses dense oxytocin binding while lower binding is detected in the medial
      anterior BST (BST-MA) and adjacent ventrolateral septum (VLS). However, in vitro
      examination of neuronal responses to oxytocin showed that the BST-LD exhibited
      small, transient responses which desensitized upon repeated challenge. In
      contrast, the BST-MA and VLS exhibited significantly larger responses with no
      significant desensitization. This inverse relationship between oxytocin binding
      density and electrophysiological responsiveness is also seen in the central and
      medial amygdaloid nuclei, which have respective associations with the lateral and
      medial divisions of the BST. Thus, excitatory responses to oxytocin vary markedly
      between BST sub-divisions and may reflect associations within the extended
      amygdala.

PMID- 15975652
TI  - N6-Cyclohexyl-adenosine but not adenosine is a modulator of teleost fish innate
      immune activities.
AB  - The possible immuneregulatory effects of two purine nucleotides, adenosine and
      cyclohexyladenosine, on gilthead seabream (Sparus aurata L.) leucocytes were
      investigated. Leucocytes isolated from the head-kidney were incubated with five
      different concentrations (ranging from 0 to 100 microM) of adenosine or
      cyclohexyladenosine for 30, 180 and 360 min and the effect on leucocyte viability
      and some of the main innate cellular immune responses was evaluated. Adenosine
      did not significantly affect the viability or the innate immune parameters of
      seabream leucocytes at any of the assayed concentrations or incubation times.
      High concentrations of cyclohexyladenosine, on the other hand, caused a
      significant drop in the respiratory burst activity of head-kidney leucocytes at
      all the times assayed. In addition, phagocytosis of yeast cells was significantly
      rapidly depressed (30 min) after incubation with 100 microM of this analogue. The
      present results demonstrate that cyclohexyladenosine at high concentrations is
      capable of down-regulating certain innate immune responses in seabream
      leucocytes, suggesting that telesot fish immune cells, like their mammal
      counterparts, possess receptors for purine nucleotides.

PMID- 15975653
TI  - The cDNA cloning and mRNA expression of a potential selenium-binding protein gene
      in the scallop Chlamys farreri.
AB  - Selenium binding proteins (SeBP) represent a family of proteins that are believed
      to be involved in controlling the oxidation/reduction in many physiological
      processes. The cDNA of Zhikong Scallop Chlamys farreri selenium binding protein
      (zSeBP) was cloned by expressed sequence tag (EST) and RACE techniques. The high
      similarity of zSeBP deduced amino acid sequence with the SeBP in other organisms,
      such as bird, fish, frog, mosquito, fruit fly, mammalian, and even nematode and
      microorganism indicated that zSeBP should be a member of SeBP family. The
      temporal expression of zSeBP in the hemocytes was measured by semi-quantitative
      RT-PCR after scallops were stimulated by either oxidative stress or microbial
      challenge. The expression of zSeBP was up-regulated progressively after
      stimulation, and then dropped gradually to the original level. Meanwhile,
      malondialdehyde (MDA) measured by the colorimetric method in the microbial
      challenged scallops increased immediately after scallops was challenged by
      microbes, and was significantly higher than that in the control scallops. Results
      indicated that the microbial infection could incense the disorder of
      oxidation/reduction and may result in high MDA production. The negative
      correlation between the expression level of zSeBP and the MDA content suggested
      that zSeBP could play an important role in mediating the anti-oxidation
      mechanisms and immune response in marine invertebrates.

PMID- 15975655
TI  - Structural but not functional conservation of an immune molecule: a tachylectin
      like gene in Hydractinia.
AB  - Tachylectin-related proteins are a recently characterized group of pattern
      recognition molecules, functioning in the innate immunity of various animals,
      from the ancient sponges to vertebrates. Tachylectins are characterized by six
      internal tandem repeats forming beta-propeller domains. We have identified and
      characterized a tachylectin-related gene in the colonial marine hydroid,
      Hydractinia echinata. The predicted gene product, termed CTRN, contained an N
      terminal signal peptide and had a well-conserved tachylectin-like structure. RT
      PCR analyses revealed only post-metamorphic expression while no mRNA was detected
      during embryonic development or in planula larvae. Exposure of colonies to LPS
      under conditions known to activate an immune response in Hydractinia did not
      result in upregulation of the gene. In situ hybridization analysis of
      metamorphosed animals detected CTRN transcripts only in a small subpopulation of
      neurons and their precursor cells, localized in a ring-like structure around the
      mouth of polyps. The same ring-like structure of CTRN expressing neurons was also
      observed in young polyp buds, predicting the position of the future mouth. This
      type of expression pattern can hardly be attributed to an immune-relevant gene.
      Thus, despite high structural similarity to tachylectins, this cnidarian member
      of this group seems to be an exception to all other tachylectins identified so
      far as it seems to have no function in cnidarian innate immunity.

PMID- 15975654
TI  - Exocytosis and proteomic analysis of the vesicle content of granular hemocytes
      from a crayfish.
AB  - The circulating blood cells (hemocytes) of invertebrates are important in
      cellular immune reactions and to deliver immune factors synthesized in these
      cells to the external milieu. Previously, we have shown that release of vesicle
      contents is involved in a regulated exocytosis and here we show which proteins in
      the vesicles are most abundant and which are released by triggering of exocytosis
      using a calcium ionophore, lipopolysaccharides-peptidoglycan and peroxinectin, a
      cell adhesion and degranulation factor from the hemocytes. The ionophore caused
      release of nine proteins and six of them were characterized and found to be a
      masquerade-like protein, a masquerade-like serine proteinase, a mannose receptor
      protein, a vitelline membrane outer layer protein I, and two anti-microbial
      peptides. The released protein band with a mass of 76 kDa is more likely pro
      phenoloxidase and/or peroxinectin. When peroxinectin was used as a trigger of
      exocytosis, seven proteins could be identified and for the lipopolysaccharides
      peptidoglycan six proteins could be identified and all of them were also released
      by the ionophore treatment. Interestingly, several anti-microbial peptides were
      the most abundant proteins and were efficiently released by all treatments as
      were two masquerade-like proteins one of which is functioning as an opsonic
      protein.

PMID- 15975656
TI  - Joint chemical flushing of soils contaminated with petroleum hydrocarbons.
AB  - How to increase the efficiency of chemical flushing and decrease the remediation
      expenses of contaminated soils are two key scientific and technological issues to
      be solved. Joint chemical flushing was tested and compared with the water
      flushing. The joint acid-flushing could effectively remove petroleum hydrocarbons
      in contaminated aquorizem and the dosage of washing powder as a flushing agent
      was greatly reduced, thereby, saving approximately 1200 US dollars of expenses
      relative to the water-flushing. The joint salt-flushing could be an optimal
      method for the cleanup of meadow burozem contaminated with petroleum hydrocarbons
      under the experimental conditions. Moreover, the amount of surfactant remained in
      the two washed soils after the joint acid-flushing and the joint-salt-flushing
      was minimal.

PMID- 15975657
TI  - Structural basis for epitope sharing between group 1 allergens of cedar pollen.
AB  - The group 1 allergens are a major cause of cedar pollen hypersensitivity in
      several geographic areas. Allergens from several taxa have been shown to cross
      react. The goal of these studies was to compare the structural features of the
      shared and unique epitopes of the group 1 allergen from mountain cedar (Jun a 1)
      and Japanese cedar (Cry j 1). An array of overlapping peptides from the sequence
      of Jun a 1 and a panel of monoclonal anti-Cry j 1 antibodies were used to
      identify the IgE epitopes recognized by cedar-sensitive patients from Texas and
      Japan. IgE from Japanese patients reacted with peptides representing one of the
      two linear epitopes within the highly conserved beta-helical core structure and
      both epitopes within less ordered loops and turns near the N- and C-termini of
      Jun a 1. A three-dimensional (3D) model of the Cry j 1, based on the crystal
      structure of Jun a 1, indicated a similar surface exposure for the four described
      epitopes of Jun a 1 and the homologous regions of Cry j 1. The monoclonal
      antibodies identified another shared epitope, which is most likely conformational
      and a unique Cry j 1 epitope that may be the previously recognized glycopeptide
      IgE epitope. Defining the structural basis for shared and unique epitopes will
      help to identify critical features of IgE epitopes that can be used to develop
      mimotopes or identify allergen homologues for vaccine development.

PMID- 15975658
TI  - The nervous system effects of occupational exposure to manganese--measured as
      respirable dust--in a South African manganese smelter.
AB  - OBJECTIVES: A major recent review of occupational exposure limits for manganese
      (Mn) has proposed a respirable dust level of 0.1 mg/m3. There is, however, no
      theoretical basis for using this exposure metric to estimate the systemic effects
      of Mn, and little in the way of empirical data relating respirable Mn to
      neurobehavioural and other non-pulmonary effects. Cross-sectional data from a
      study showing few and unconvincing neurobehavioural effects of inhalable dust in
      Mn smelter workers published just prior to this review were reanalyzed here using
      respirable Mn. The hypotheses tested were that respirable Mn exposure is a more
      appropriate predictor of neurobehavioural effects than inhalable Mn where such
      effects exist, and that there should be no observed effects at respirable dust
      levels below 0.1 mg/m3. METHODS: Five hundred and nine production workers and 67
      external referents were studied. Exposure measures from personal sampling
      included the Mn content of respirable dust as a concentration-time integrated
      cumulative exposure index (CEI) and as average intensity (INT) over a working
      lifetime. Neurobehavioural endpoints included items from the Swedish nervous
      system questionnaire (Q16), World Health Organisation neurobehavioural core test
      battery (WHO NCTB), Swedish performance evaluation system (SPES), Luria-Nebraska
      (LN), and Danish Product Development (DPD) test batteries, and a brief clinical
      examination. RESULTS: The median respirable Mn exposure was 0.058 mg/m3 (range=0
      0.51; IQR=0.02-0.16) amongst the exposed, with 30% having average intensities
      above the proposed 0.1 mg/m3 and 44% above the proposed supplemental limit of 0.5
      mg/m3 inhalable dust. As in the study of inhalable Mn effects, there were few
      respirable Mn effects showing clear continuity of response with increasing
      exposure. CONCLUSION: These data did not provide empirical support for a
      respirable, as opposed to an inhalable, dust metric being more sensitive in the
      identification of Mn effects. Neither metric showed convincing effects within the
      exposure range studied. Further study is needed to determine a threshold for
      respirable Mn effects, if such exist, and to verify our findings.

PMID- 15975659
TI  - Development of a screen-printed carbon electrochemical immunosensor for picomolar
      concentrations of estradiol in human serum extracts.
AB  - Investigations into the development of a prototype electrochemical immunosensor
      for estradiol (E(2)) are described. After optimising reagent loadings in a 96
      well enzyme-linked immunosorbent assay (ELISA), antibodies (rabbit anti-mouse IgG
      and monoclonal mouse anti-E(2)) were immobilised by passive adsorption onto the
      surface of screen-printed carbon electrodes (SPCEs). A competitive immunoassay
      was then performed using an alkaline-phosphatase (ALP)-labelled E(2) conjugate.
      Calibration plots for E(2) buffer standards, performed colorimetrically on the
      SPCEs using a para-nitrophenyl phosphate substrate solution, were in good
      agreement with ELISA calibration plots. Electrochemical measurements were then
      performed using differential pulse voltammetry (DPV) following the production of
      1-naphthol from 1-naphthyl phosphate. The calibration plot of DPV peak current
      versus E(2) concentration showed a measurable range of 25-500 pg/ml with a
      detection limit of 50 pg/ml. A coefficient of variation of between 13.0 and 15.6%
      was obtained for repeat measurements. The immunosensor was applied to the
      determination of E(2) in spiked serum, following an extraction step with diethyl
      ether. A mean recovery for the method of 102.5% was obtained with a CV of 19.1%.
      The options available for further development of the sensor regarding precision,
      limit of detection and direct sample analysis are discussed.

PMID- 15975660
TI  - Effect of nano cadmium sulfide on the electron transfer reactivity and peroxidase
      activity of hemoglobin.
AB  - Hemoglobin (Hb) is immobilized with cadmium sulfide (CdS) nanoparticles (NPs) on
      pyrolytic graphite (PG) electrode to characterize the electrochemical reactivity
      and peroxidase activity of the protein. The result demonstrates that fine redox
      waves of Hb can be achieved after this protein is entrapped in CdS NPs.
      Meanwhile, the protein can exhibit nice catalytic activity towards hydrogen
      peroxide (H2O2). Linear relationship between the reductive peak current and the
      H2O2 concentration has been obtained from 5.0 x 10(-6) to 4.0 x 10(-4) mol/L, on
      the basis of which a new kind of H2O2 biosensor might be developed in the future.

PMID- 15975661
TI  - Optimization and design of oligonucleotide setup for strand displacement
      amplification.
AB  - Several advantages of strand displacement amplification (SDA) as an all-purpose
      DNA amplification reaction are due to it isothermal mechanism. The major problem
      of isothermal amplification mechanism is the accumulation of non-predictable
      byproduct especially for longer incubation time and low concentrations of initial
      template DNA. New theoretical strategies to tackle the difficulties regarding the
      specificity of the reaction are experimentally verified. Besides improving the
      reaction conditions, the stringency of primer hybridization can be distinctly
      improved by computer based sequence prediction algorithms based on the
      thermodynamic stability of DNA hybrid a described by the partition function of
      the hybridization reaction. An alternative SDA mechanism, with sequences
      developed by this means is also investigated.

PMID- 15975662
TI  - Transfemoral selective "intraluminal wiring" technique for transient middle
      cerebral artery occlusion in rats.
AB  - While the intraluminal thread technique to induce middle cerebral artery
      occlusion is widely used in animal models of focal cerebral ischemia, it has
      several drawbacks. The present study describes a new technique involving
      transfemoral selective intraluminal wiring, and evaluates its technical
      feasibility, effectiveness, and safety. Twenty-four Wistar rats were used in this
      work: two for a vascular anatomy study and 22 subjected to middle cerebral artery
      occlusion for 1 h by our new transfemoral selective "intraluminal wiring"
      technique. After 24 h of reperfusion, the animals were evaluated neurologically,
      and then were sacrificed. Macroscopic, histological (2,3,5-triphenyltetrazolium
      chloride (TTC), hematoxylin-eosin and TUNEL), and biochemical (DNA fragmentation
      and caspase-3 activity) studies were performed to assess the extent of brain
      damage produced by focal ischemia. Technical success was obtained in all 22
      animals. Signs of focal ischemia and reperfusion, such as necrosis and apoptosis,
      were detected in the middle cerebral artery territory. No subarachnoid hemorrhage
      was noticed in any animal. Transfemoral selective intraluminal wiring appears to
      be a reliable, safe, and minimally invasive technique to induce transient focal
      cerebral ischemia in rats.

PMID- 15975663
TI  - Optimization of oligodendrocyte progenitor cell culture method for enhanced
      survival.
AB  - Oligodendrocyte progenitor cells (OPCs, NG2 glia) play an important role not only
      as progenitor cells that give rise to myelinating cells in the central nervous
      system (CNS), but also as an active participant in the neural network. It is
      necessary to develop a simplified method for generating large quantities of
      highly purified OPCs for biochemical studies and to establish a neuron-OPC
      coculture method for functional studies on the mechanism of neuron-OPC signaling.
      In this study, we have compared the effects of plating density and culture medium
      on purity, survival, and differentiation of cells collected from primary rat
      mixed glial cultures by differential adhesion. Comparison of two chemically
      defined culture media, Dulbecco's modified Eagle's medium with N1 supplements
      (N1/DMEM) and Neurobasal medium with B27 supplements (B27/NBM) revealed that
      while both media successfully maintained greater than 90% pure OPCs after 3 days,
      B27/NBM was significantly more effective in maintaining viable cells and in
      supporting oligodendrocyte differentiation than N1/DMEM, and this effect was more
      pronounced in low density cultures. Furthermore, B27/NBM supported neuron-OPC
      coculture in which OPCs remained as NG2-positive progenitors and neurons
      differentiated to form synapses over a period of 3 weeks.

PMID- 15975665
TI  - Expression pattern of adaptor protein PAG: correlation between secondary
      lymphatic follicle and histogenetically related malignant lymphomas.
AB  - Transmembrane adaptor protein PAG, also known as Csk-binding protein (Cbp), which
      binds and activates the cytoplasmic tyrosine kinase Csk, the major negative
      regulator of Src-family kinases, was found to be expressed in germinal centers of
      lymphoid follicles as well as in follicular, but not mantle cell lymphomas.
      Expression of PAG may reflect its role in regulation of proliferation and
      differentiation of germinal center B-cells. From the routine histopathology point
      of view, PAG might be a new positive marker of follicular lymphoma and a negative
      marker of mantle cell lymphoma.

PMID- 15975664
TI  - Voltammetric study of extracellular dopamine near microdialysis probes acutely
      implanted in the striatum of the anesthetized rat.
AB  - Establishing in vivo microdialysis methods for the quantitative determination of
      dopamine concentrations in the extracellular space of the brain is an important
      yet challenging objective. The source of the challenge is the difficulty in
      directly measuring the microdialysis recovery of dopamine during an in vivo
      experiment. The recovery value is needed for quantitative microdialysis,
      regardless of whether conventional or no-net-flux methods are used. Numerical
      models of microdialysis that incorporate both diffusion and active transport
      processes suggest that dopamine recovery is strongly affected by processes
      occurring in the tissue closest to the probe. Some evidence suggests that the
      tissue adjacent to the probe becomes disrupted during probe implantation. Hence,
      the objective of the present study was to further identify whether the tissue
      adjacent to the probe is disrupted and, if so, whether that disruption might
      affect dopamine recovery. The experiments were conducted with microdialysis
      probes implanted acutely in the striatum of rats anesthetized with chloral
      hydrate. Carbon fiber voltammetric microelectrodes were used to monitor
      extracellular dopamine at three sites near the probes; immediately adjacent to
      the probe, 220-250 microm from the probe, and 1 mm from the probe. Probes were
      lowered slowly over a 30 min period, so that dialysate dopamine levels were
      stable, in the low nanomolar range, and partially TTX-sensitive by the time
      experiments began. Starting 2h after probe implantation, dopamine was monitored
      by fast-scan cyclic voltammetry during electrical stimulation of the medial
      forebrain bundle and during administration of the dopamine uptake inhibitor,
      nomifensine. The findings of this study show that a gradient of dopamine release
      and uptake activity extends at least 220 microm from microdialysis probes
      implanted acutely in the striatum of the anesthetized rat.

PMID- 15975666
TI  - Salmonella flagellin, a microbial target of the innate and adaptive immune
      system.
AB  - Bacterial flagellins are important components of the motility apparatus used by
      many microbial pathogens. These proteins are also targets of the innate and
      adaptive immune response of the host during infection and autoimmune disease.
      Flagellin interacts with TLR-5 and leads to the generation of a pro-inflammatory
      response and activation of host dendritic cells in vivo. Furthermore, flagellin
      is recognized by antibody and CD4 T cells responses during Salmonella infection.
      Here, we review recent developments in the understanding of flagellin
      interactions with the host immune system.

PMID- 15975668
TI  - A human glucagon-like peptide-1 receptor polymorphism results in reduced agonist
      responsiveness.
AB  - Glucagon-like peptide-1 (GLP-1) and its cognate receptor play an important
      physiological role in maintaining blood glucose homeostasis. A GLP-1 receptor
      (GLP-1R) polymorphism in which threonine 149 is substituted with a methionine
      residue has been recently identified in a patient with type 2 diabetes but was
      not found in non-diabetic control subjects. We have functionally assessed the
      recombinant GLP-1R variant after transient expression in COS-7 and HEK 293 cells.
      Compared to the wild type receptor, the variant GLP-1R showed (i) similar
      expression levels, (ii) 60-and 5-fold reduced binding affinities, respectively,
      for two GLP-1R full agonists, GLP-1 and exendin-4, and (iii) markedly decreased
      potencies of these peptides in triggering cAMP-mediated signaling (despite
      conserved efficacies). In contrast to full agonists, the efficacy of the primary
      GLP-1 metabolite/GLP-1R partial agonist, GLP-1 (9-36) amide, was essentially
      abolished by the T149M substitution. By hydropathy analysis, the polymorphism
      localizes to transmembrane domain 1, suggesting this receptor segment as a novel
      determinant of agonist affinity/efficacy. These findings reveal that naturally
      occurring sequence variability of the GLP-1R within the human population can
      result in substantial loss-of-function. A genetic link between the T149M variant
      and increased susceptibility to type 2 diabetes remains to be established.

PMID- 15975667
TI  - Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5
      methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages.
AB  - Inflammation is a complex phenomenon involving multiple cellular and molecular
      interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key
      enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from
      arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical
      role in the inflammatory response and its over-expression has been associated
      with several pathologies including neurodegenerative diseases and cancer.
      Melatonin is the main product of the pineal gland with well documented
      antioxidant and immuno-modulatory effects. Since the action of the indole on COX
      2 has not been previously described, the goal of the present report was to test
      the effect of melatonin on the activities of COX-2 and inducible nitric oxide
      synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages
      as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5
      methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2
      activation induced by LPS, without affecting COX-1 protein levels. The
      structurally related compound 6-methoxy-melatonin only partially prevented the
      increase in COX-2 protein levels induced by the toxin. Likewise melatonin
      prevented iNOS activation and reduced the concentration of products from both
      enzymes, PGE(2) and nitric oxide. Another endogenous antioxidant like N-acetyl
      cysteine (NAC) did not reduced COX-2 significantly. The current finding
      corroborates a role of melatonin as an anti-inflammatory agent and, for the first
      time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites
      AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated
      by the free radical scavenging properties of melatonin. As a consequence, the
      present work suggests these substances as a new class of potential anti
      inflammatory agents without the classical side effects due to COX-1 inhibition.

PMID- 15975669
TI  - Microalbuminuria as a marker of cardiovascular risk in patients with type 2
      diabetes.
AB  - Diabetes is a major risk factor for coronary artery disease and most patients
      with diabetes die of cardiovascular complications. Reduction of cardiovascular
      risk is therefore a high priority in the management of patients with diabetes.
      Microalbuminuria is an important predictor of cardiovascular events and forms one
      of the components of the insulin resistance/metabolic syndrome, which confers a
      particularly high risk of cardiovascular death. The currently available glucose
      lowering agents vary considerably in their ability to reduce microalbuminuria.
      The sulfonylureas and metformin appear to have little effect on microalbuminuria
      expressed as urinary albumin/creatinine ratio, while the thiazolidinediones have
      unique effects on this risk factor, in parallel with their effects on insulin
      resistance. In two 1-year European multicenter, randomized, double-blind
      monotherapy trials (n=2444), pioglitazone produced similar reductions in urinary
      albumin/creatinine ratio to gliclazide and greater reductions than metformin
      (P<0.001). Similarly, two further 1-year European multicenter, randomized, double
      blind trials assessed the effects of add-on therapy (n=1269) on urinary
      albumin/creatinine ratio. In the first study, urinary albumin/creatinine ratio
      was reduced by pioglitazone add-on to sulfonylurea (-15%), but was largely
      unaffected by metformin add-on to sulfonylurea (2%; P<0.05). In the second,
      urinary albumin/creatinine ratio was also reduced by pioglitazone add-on to
      metformin (-10%), but increased by gliclazide add-on to metformin (6%, P<0.05).
      The results of these studies indicated that compared with metformin or
      gliclazide, pioglitazone may provide therapeutic benefits, over and above those
      due to improved glycemic control. These include significant reductions in urinary
      albumin/creatinine ratio, a known cardiovascular risk marker.

PMID- 15975670
TI  - Clinical predictors of cardiac events in patients with isolated syncope and
      negative electrophysiologic study.
AB  - BACKGROUND: Patients with syncope or near syncope of unknown etiology represent a
      great challenge to cardiologists. An initial symptomatic episode triggers a
      series of diagnostic analysis which remain unsatisfactory when negative. More
      invasive tools such as electrophysiologic testing yield only partial answers to
      risk stratification while the complementary implantable holter diagnostics are
      not usually considered until a recurrent episode is documented. OBJECTIVE: This
      study targets predictors of significant cardiac rhythmic events in patients with
      a reported episode of syncope or near syncope presenting with negative
      diagnostics and electrophysiologic study results (EPS). A significant cardiac
      rhythmic event was defined as a combined end-point of (1) symptomatic AV block;
      (2) symptomatic conduction abnormalities requiring pacemaker therapy; (3)
      symptomatic sustained ventricular arrhythmia; and (4) sudden death. METHODS: All
      patients undergoing EPS after a first episode of syncope or presyncope between
      January 1997 and December 2001 were included for analysis. The study population
      consisted of 329 pts (42.6% women), 21 to 96 years old (mean 70+/-15 years)
      referred for an EP study for syncope or near syncope. RESULTS: Of the 329
      patients who underwent EPS, 305 (92.7%) had follow-up data. The population, mean
      age 70 (+/- 15 years) and composed of 42% women, presented with hypertension
      (51.5%), diabetes mellitus (14.4%), hypercholesterolemia (30%), tobacco use
      (35%), a familial history of coronary heart disease (22%), history of stroke
      (4%), history of MI (12%), history of atrial fibrillation (10%), structural heart
      disease (17.4%), left ventricular ejection fraction 61 (+/- 11%) and ECG
      abnormalities (37%). These anomalies included right (RBBB) or left (LBBB) bundle
      branch blocks, left anterior fascicular block (LAFB), left posterior fascicular
      block (LPFB), bifascicular block (RBBB+LAFB) and traces of myocardial infarction.
      The mean follow-up was 31+/-20 months with 5% of patients recording significant
      cardiac rhythmic events (15/305): AV block requiring pacemaker therapy in 7
      patients, sinus dysfunction in 4, sudden death in 3 and ventricular tachycardia
      in 1. Univariate analysis reveals structural heart disease, ECG abnormalities and
      LVEF associated with the risk of significant cardiac rhythmic events defined by
      the combined end-point. Multivariate analysis using a Cox model found that the
      only independent predictor of events was an ECG abnormality. The long-term risk
      of significant event in the subset with ECG abnormalities is of 10.6% (12/113).
      If unexplained syncope recurrence was included in the combined end-point, ECG
      abnormality and LVEF were both determinants with a 13.3% (15/113) risk of a
      arrhythmic events analysis in the subset of patients presenting with ECG
      abnormalities and Cox model found ECG abnormality as the only independent
      predictor of event. CONCLUSIONS: This study demonstrated that an ECG abnormality
      is the only predictive variable associated with a significant arrhythmic event in
      patients with a lone episode of syncope or near syncope and a negative EPS.

PMID- 15975672
TI  - Reduced risks of death and CHF are associated with statin therapy administered
      acutely within the first 24 h of AMI.
AB  - BACKGROUND: Reports have demonstrated an association between statin therapy
      during the first day of hospitalization for acute myocardial infarction (AMI) and
      reduced mortality. There are little data about whether early statin therapy
      reduces risk of CHF and alters timing of death. METHODS: We identified 3226
      consecutive patients with AMI from 1993 through 2000 and divided them into early
      statin therapy (statins were administered within the initial 24 h of
      hospitalization, n=220) and non-statin therapy groups (n=3006). We compared
      mortality risks, rates of CHF development and measures of peak CK and CK-MB
      values between the groups. RESULTS: In-hospital mortality was lower in the early
      statin therapy group (2.7%) compared to the non-statin therapy group (9.2%),
      p=0.001. We observed no differences in the median time to death (statin group 132
      h vs. non-statin group 72 h), p=0.3. Patients with very early statin treatment
      had lower peak CK (624 ng/ml) and CK-MB (46 ng/ml) values compared to non-statin
      patients (848 ng/ml and 84 ng/ml), p<0.01. Patients in the early statin group had
      lower risks of developing CHF during hospitalization (10.2 %) compared to the non
      statin group (25.7%), p<0.001. CONCLUSION: Very early administration of statin
      therapy during the first day of hospitalization for AMI was associated with lower
      in-hospital mortality, lower rates of developing CHF and reduced peak biomarker
      release. These data support a benefit from early statin therapy in AMI and
      support the need for prospective studies which test whether very early statin
      therapy might also reduce infarct size.

PMID- 15975671
TI  - Clinical characteristics of acute pulmonary thromboembolism in Korea.
AB  - BACKGROUND: Acute pulmonary thromboembolism (APTE) remains an important cause of
      morbidity and mortality in Western countries. In Korea, both the incidence and
      the mortality rate of APTE were thought to be low compared to Western countries.
      We performed the present study to investigate the current status of APTE in
      Korea. METHODS: Eight hundred and eight registry patients with APTE were analyzed
      with respect to clinical symptoms and signs, the presence of underlying diseases
      or predisposing factors, diagnostic methods, treatment and clinical course.
      RESULTS: The most common risk factors were prolonged immobilization (22.9%), deep
      venous thrombosis (22.0%), a recent operation (19.2%), and cancer (15.8%). The
      most common symptoms were dyspnea (78.6%), and chest pain (26.9%). The most
      common abnormality on chest radiography was effusion. The overall mortality rate
      at 3 months was 11.0%. Multivariate logistic regression analysis demonstrated
      that increased mortality risk was independently associated with the following
      baseline factors: onset in hospital (OR 1.88; 95% CI 1.03-3.42; p=0.03), lung
      cancer (OR 9.20; 95% CI 1.96-43.27; p=0.005), tachycardia (OR 3.50; 95% CI 1.86
      6.60; p=0.0001), cardiogenic shock (OR 6.74; 95% CI 2.73-16.64; p=0.0001), and
      cyanosis (OR 3.45; 95% CI 1.27-9.44; p=0.01). CONCLUSIONS: Some differences did
      exist for the risk factors, symptoms, chest X-ray findings, mortality rate and
      prognostic factors as compared with those for Western patients. These results can
      prove especially helpful in the diagnosis as well as for the treatment of
      patients with APTE.

PMID- 15975673
TI  - Evaluation of current and novel protocols for disinfection of airplane passenger
      footwear under simulated conditions.
AB  - Aerobic bacterial culture was used to compare the effectiveness of the current
      USDA footwear disinfection protocol for airplane passengers contacting livestock
      to a novel protocol. The current protocol consists of brushing and dipping shoe
      soles in 1% Virkon S. The number of bacteria was not different between shoes
      treated with the current protocol and untreated shoes. No shoes met the standard
      for disinfection after the current disinfection protocol was completed. The novel
      protocol consisted of brushing shoe soles, wiping soles with a cotton towel
      soaked in 1% Virkon S, and drying soles with paper towels. The number of bacteria
      was less (P<0.0001) on treated shoes compared to control shoes. Eighteen of 20
      shoes (90%) cleaned using the novel protocol met the standard for disinfection.
      Direct comparison of the current and novel protocols found that the number of
      bacteria cultured was less (P<0.0001) after implementing the novel protocol
      compared to implementing the current protocol. Again, no shoes treated using the
      current protocol met the standard for disinfection after the current protocol was
      completed. Sixteen and 17 of 20 shoes (80--85%), respectively, met the standard
      for disinfection after the novel protocol was completed. Under conditions of this
      study, current US airport footwear disinfection protocols were inadequate to
      disinfect footwear when using aerobic bacteria as a marker for disinfection. We
      recommend implementation of the novel footwear disinfectant protocol for select
      passengers from international flights.

PMID- 15975675
TI  - Airflow and autonomic responses to stress and relaxation in asthma: the impact of
      stressor type.
AB  - The impact of stress on respiratory airflow in asthmatics is unclear. Part of the
      uncertainty may spring from the different physiological effects of different
      stressors. Given their potential to elicit increases in parasympathetic vagal
      activity, stressful situations that present few opportunities for coping (passive
      coping stressors) may be particularly problematic for people with asthma. Thirty
      one adult asthmatics participated in a protocol including a widely used passive
      coping stressor (the cold pressor test), an active coping stressor (mental
      arithmetic), an interview about an upsetting asthma-related incident (viewed as a
      potential passive coping stressor given the exposure to unpleasant memories), and
      progressive muscle relaxation. Repeated measurements of airflow (via peak
      expiratory flow), vagal tone (via heart rate variability), and other variables
      were obtained. The cold pressor test, asthma interview and progressive muscle
      relaxation produced significant decreases in airflow compared to the baseline
      period. The cold pressor test and progressive muscle relaxation produced
      significant, complementary increases in vagal tone. These results suggest that
      passive coping stressors and other stimuli (e.g., certain forms of relaxation)
      that elicit increased vagal tone may be associated with poorer asthma control, a
      view consistent with a significant negative correlation between the participant's
      mean vagal tone response to the tasks and score on a measure of asthma self
      efficacy.

PMID- 15975676
TI  - Evolution of Listeria populations in food samples undergoing enrichment
      culturing.
AB  - The isolation of Listeria monocytogenes from food is carried out using a double
      enrichment. It is believed that the double enrichment can allow the overgrowth of
      Listeria innocua in samples where both species are present. In this study, we
      have evaluated the impact of overgrowth between Listeria species and strains
      during each step of the enrichment process. The effect of factors minimizing
      interactions between strains or phage inhibitory effects has also been estimated.
      In an artificially contaminated food undergoing enrichment, overgrowth could
      result from competitive interactions between Listeria spp. resulting from the
      production of bacteriocins and bacteriophage at high initial contamination levels
      (>10(4) cfu/g), but not at lower levels (50-100 cfu/g) as generally found in
      contaminated foods. At high levels of inoculation, the competitive effect could
      be reduced by solidification of the selective broths, to limit the diffusion of
      the inhibitors. Overgrowth resulting from differences in growth rate occurred
      independent of the initial contamination level. However, in naturally
      contaminated foods undergoing enrichment, there were no absolute correlations
      between growth rates or inhibitory profiles in terms of strain evolution during
      enrichment. In fact, Listeria strains which were predominant in the original
      sample in most cases remained the dominant strains at the end of the enrichment,
      although the relative proportion of any given strain could change significantly
      over the enrichment process. Additional factors which have yet to be identified
      impact on the evolution of Listeria in the two-step enrichment process. Analysis
      of strain evolution in eight naturally contaminated foods has indicated that the
      second enrichment step in Fraser broth can be reduced from 48 to 24 h without
      impacting on the recovery of L. monocytogenes. Our limited survey of naturally
      contaminated foods also demonstrated that maximum recovery of L. monocytogenes
      and other Listeria strains was found following 24 h incubation in 1/2 Fraser
      Broth. This finding suggests that it may be possible to shorten the current two
      step isolation method further without reducing method sensitivity.

PMID- 15975677
TI  - Cheesemaking with a Lactococcus lactis strain expressing a mutant oligopeptide
      binding protein as starter results in a different peptide profile.
AB  - Lactic starters used for cheese manufacture play an important role in the
      production of bitter peptides and their degradation to non-bitter products. The
      oligopeptide transport system (Opp) of lactococci is essential for milk peptide
      utilization. The periplasmic substrate binding protein serves to capture the
      substrate with high affinity and to deliver it to a membrane-bound complex that
      translocates it inside the cell. Prt(+)- and Lac(+)-derivatives of MG1363
      DeltaoppA strains expressing a wild-type MG1363 OppA or a mutant OppA with a
      single point mutation at residue 471 (OppA(D471R)) from a plasmid were
      constructed. These strains were used as lactic starters in cheese manufacture to
      improve flavour quality by removing hydrophobic peptides from the cheese matrix,
      through their preferential transport by OppA(D471R). Cheeses made with these
      strains were not significantly different from control cheeses after 1 day of
      ripening with respect to bacterial counts, pH and proteolysis, and only slight
      differences were recorded after 9 and 20 days of ripening. HPLC chromatograms of
      the hydrophilic and hydrophobic peptides present in the water-soluble fraction of
      experimental cheeses showed significant differences in peptide content as well as
      in peak profiles. These results suggest a different peptide utilization in the
      strain expressing OppA(D471R) and make it suitable for use as starter to improve
      cheese quality.

PMID- 15975678
TI  - Two primer pairs to detect OTA producers by PCR method.
AB  - Fungi contaminating foods and feeds may produce many mycotoxins including
      ochratoxin A (OTA). Early and rapid detection of potential OTA producing fungi is
      important to reduce the negative impacts of OTA. In this study, two PCR specific
      primer pairs, AoLC35-12L/AoLC35-12R and AoOTAL/AoOTAR, were designed from a DNA
      sequence of a polyketide synthase gene in Aspergillus ochraceus NRRL 3174. On 14
      different fungi tested by PCR, AoLC35-12L/AoLC35-12R amplified a unique band from
      either OTA or citrinin producers while AoOTAL/AoOTAR amplified one PCR product
      only from A. ochraceus. So these primers could be used to detect both OTA and
      citrinin producing fungi (AoLC35-12L/AoLC35-12R) or only A. ochraceus
      (AoOTAL/AoOTAR) from foodstuffs using PCR method.

PMID- 15975679
TI  - Characterization of a reuterin-producing Lactobacillus coryniformis strain
      isolated from a goat's milk cheese.
AB  - Lactobacillus coryniformis CECT 5711, a strain isolated from a goat's milk
      cheese, displayed a broad-spectrum antimicrobial activity; as a consequence, its
      ability to produce the antagonistic compounds associated to lactic acid bacteria,
      including bacteriocins, hydrogen peroxide, lactic acid, acetic acid, and reuterin
      (3-hydroxypropionaldehyde, 3-HPA) was investigated. Production of bacteriocins or
      hydrogen peroxide by this strain could not be detected. However, in addition to
      lactic acid and acetic acid, it produced reuterin and cobalamin, a cofactor
      required for conversion of glycerol to 3-HPA through a glycerol dehydratase. The
      gene encoding a glycerol dehydratase subunit was detected by PCR and the
      corresponding amplicon was sequenced. This strain showed a high survival after
      exposition to conditions simulating those existing in the gastrointestinal tract
      as well as a notable ability to adhere to intestinal cells, which suggests that
      its reuterin-producing ability may be used for the host benefit. In addition, the
      strain showed a strong beta-galactosidase activity. Production of biogenic amines
      and degradation of mucin could not be detected.

PMID- 15975680
TI  - SMGA gels for the skin permeation of haloperidol.
AB  - Small molecule gelling agent (SMGA) gels were developed using the gelator GP-1 in
      the solvents, namely, isostearyl alcohol (ISA) and propylene glycol (PG), to
      deliver haloperidol through the skin. The concentrations of the drug,
      haloperidol, the enhancer, farnesol and the gelator, GP-1 are 3 mg/ml, 5% (w/v)
      and 5% (w/v), respectively. The study employed a three-factor full factorial
      statistical design to investigate the influence of factor level changes on the
      permeability coefficient and permeation lag-time of haloperidol. Gels were
      prepared by raising temperature to 120 degrees C, followed by natural cooling
      under room temperature of 22+/-1 degrees C. The rheological properties of the
      gels were examined with a strain-controlled dynamic mechanical method. The in
      vitro permeation study was conducted with automated flow-through type cells. The
      gels successfully incorporated the drug and enhancer without losing their
      aesthetic properties. The in vitro human skin permeation study showed the
      permeation of the drug in ISA-based gels reached the pseudo steady state faster
      than PG-based gels and were less affected by gelator. PG-based gels delivered the
      drug at a faster rate with the incorporation of the enhancer. GP-1 did not
      influence the drug permeation rate but it increased permeation lag-time. The co
      existence of gelator or enhancer increased the lag-time to a larger extent than
      when used separately. The novel SMGA gels are suitable for topical or transdermal
      delivery.

PMID- 15975681
TI  - [Spinal manipulation: survey of French medical physicians who graduated with the
      national diploma of osteopathy from Strasbourg University].
AB  - INTRODUCTION: The use of spinal manipulation (SM) is widespread, particularly in
      English-speaking countries, where many studies are published showing its
      popularity. However, no study exists of the demography and activity of the French
      medical profession. Our objective was to investigate the use of SM by French
      doctors in their daily practice. MATERIALS AND METHODS: We questioned 234
      doctors, general practitioners and specialists who obtained the Inter-Academy of
      Manual Medicine and Osteopathy Diploma from Strasbourg University between 1985
      and 2002. RESULTS: We obtained a response from 140 physicians: 110 (79%)
      practiced SM in their daily practice. They considered the technique efficient and
      used it as a first intention. Approximately one quarter of cases resulted in
      adverse effects on the back. Most of the doctors (77%) continued their education
      during their career. CONCLUSION: This first assessment of the practice of
      physicians trained in a university in manual medicine allows for confirming the
      respect of good medical practice with regular actualization of knowledge and
      reasonable outpatient care.

PMID- 15975682
TI  - [Personal experience of adolescents with a brain-injured parent: preliminary
      study].
AB  - OBJECTIVE: To explore the impact of brain injury of a parent on adolescent
      behavioural and emotional symptoms and personal experience. PATIENTS AND SETTING:
      Eleven adolescents from 13 to 18 years old with a brain-injured parent with
      cognitive impairment. MAIN OUTCOME MEASURES: Multiple case report. Assessment of
      anxiety and depression on the R-CMAS scale and the BDI. Qualitative analysis of a
      semi-structured interview and of the family drawing. RESULTS: Pathological scores
      on the R-CMAS scale involved 36% of the cases and the BDI, 45%. Impulsivity
      involved 36% of cases, difficulties in learning at school 73%, and somatic
      symptoms 45%. Feeling of loneliness involved 64% of cases and difficulty for the
      adolescent to speak about feelings in the family 82%. The symbolic position of
      the brain-injured parent was maintained in all cases. In 45% of cases, the parent
      was unable to recognize the adolescent, and in 55%, some characteristics of the
      adolescent were linked to the illness of the parent. A feeling of insecurity
      pervaded all cases. The family drawing revealed abnormalities in the bodily
      representation of the family members, especially a lack of hands or a
      representation of amputated hands in 91% of the cases and unsteadiness of the
      family members, also represented as ghosts in 82% of cases. CONCLUSION: Living
      with a brain-injured parent increases depression disorders, a feeling of
      loneliness and insecurity in adolescents. The inability for the adolescent to
      recognize parent's personality and the identification with caracteristics of the
      parent due to the illness is worrying. Abnormalities in the bodily representation
      of the family members and their unsteadiness are characteristic signs.

PMID- 15975683
TI  - Enterohepatic transport of bile salts and genetics of cholestasis.

PMID- 15975684
TI  - Adefovir-lamivudine combination therapy and hepatitis B viral kinetics.

PMID- 15975685
TI  - Maintained cerebral and skeletal muscle oxygenation during maximal exercise in
      patients with liver cirrhosis.
AB  - BACKGROUND/AIMS: In cirrhotic patients, insufficient redistribution of blood from
      splanchnic organs to the central circulation could limit blood supply to skeletal
      muscles and the brain during exercise. METHODS: Eight cirrhotic patients
      performed incremental cycling to exhaustion (74 (49-123) W; median with range).
      RESULTS: Heart rate increased from 68 (62-88)beats/min at rest to 142 (116
      163)beats/min, cardiac output from 5.1 (3.3-7.2) to 12.9 (8.5-15.9)l/min, and
      mean arterial pressure from 89 (75-104) to 115 (92-129)mmHg (P<0.05), while the
      indocyanine green elimination determined hepatosplanchnic blood flow declined
      from 0.97 (0.55-1.46) to 0.62 (0.36-1.06)l/min (P<0.05). As assessed by near
      infrared spectrophotometry, cerebral oxygenation (NIRS) was 61% (48-85%) and
      increased to 72% (57-86%) during exercise (P<0.05). The NIRS determined
      oxygenation of the vastus lateralis muscle also increased: the concentrations of
      oxygenated haemoglobin by 5.9 (0.57-9.47)micromol/l, deoxygenated haemoglobin by
      7.2 (1.8-12.0)micromol/l, and thus total haemoglobin by 12.1 (3.6-21.5)micromol/l
      (P<0.05). CONCLUSIONS: In patients with cirrhosis, exercise reduces
      hepatosplanchnic blood flow, while O(2) supply to muscle and brain appears to
      increase indicating that blood redistribution from splanchnic organs does not
      limit blood flow to working muscles and the brain.

PMID- 15975686
TI  - The questionable role of immunization against hepatitis B in HBV infected liver
      transplant patients.

PMID- 15975687
TI  - Positron emission tomography is not a reliable method for the early diagnosis of
      cholangiocarcinoma in patients with primary sclerosing cholangitis.

PMID- 15975688
TI  - The impact of loss of Medicaid on health service utilization among persons with
      HIV/AIDS in New York City.
AB  - OBJECTIVES: To examine predictors of losing Medicaid and the impact of losing
      Medicaid on health service utilization for persons living with HIV/AIDS. DESIGN:
      The data are from the Community Health Advisory and Information Network (CHAIN),
      an on-going longitudinal survey representative of adults with HIV/AIDS in NYC (N
      = 698) (1994-1997 data). Change of Medicaid coverage between survey waves was
      considered a "transition" yielding three groups: "no transition", "transition to
      insurance", and "transition to no insurance". METHODS: To determine predictors of
      transitions and the impact of transitions on health service utilization,
      multinomial logistic regression was used to compare the three groups. RESULTS:
      There were 114 transitions and 792 cases without transitions, with transitions
      decreasing over time. Thirty percent of transitions were from Medicaid to no
      insurance. Transitions to insurance were more likely among the employed and those
      with incomes over 15,000 US Dollar. Transitions to no insurance were more likely
      among AIDS cases, recent immigrants, and people less than 30-year-old. People in
      both transition groups were less likely than people who retained Medicaid to have
      experienced a life event in the pre-transition period. Those with transitions to
      insurance reported decreased hospital and drug treatment. People who became
      uninsured reported decreased use of routine and preventive care, decreased health
      information and advice and decreased use of private doctors and outpatient
      clinics. CONCLUSION: While the rate of transitions from Medicaid was relatively
      low, such transitions were associated with greater variability in quality of
      health care and greater difficulty accessing primary care among the uninsured.

PMID- 15975689
TI  - Data reduction in headspace analysis of blood and urine samples for robust
      bacterial identification.
AB  - This paper demonstrates the application of chemical headspace analysis to the
      problem of classifying the presence of bacteria in biomedical samples by using
      computational tools. Blood and urine samples of disparate forms were analysed
      using a Cyrano Sciences C320 electronic nose together with an Agilent 4440
      Chemosensor. The high dimensional data sets resulting from these devices present
      computational problems for parameter estimation of discriminant models. A variety
      of data reduction and pattern recognition techniques were employed in an attempt
      to optimise the classification process. A 100% successful classification rate for
      the blood data from the Agilent 4440 was achieved by combining a Sammon mapping
      with a radial basis function neural network. In comparison a successful
      classification rate of 80% was achieved for the urine data from the C320 which
      were analysed using a novel nonlinear time series model.

PMID- 15975690
TI  - Multiple correspondence analysis in S-PLUS.
AB  - Multiple correspondence analysis (MCA) is a multivariate method for analyzing
      multidimensional contingency tables. General software procedures to perform MCA
      are available. Among them SAS Proc CORRESP, SPAD CORMU procedure and the mca
      function of the MASS library in S-PLUS are probably the most used. However,
      CORRESP and CORMU output is different from that of mca function. The aim of this
      short note is showing how to obtain from mca function results compatible with
      those achieved with SAS or SPAD. A modified code is proposed in order to obtain
      the same coordinate system computed by SAS and SPAD. Moreover, the computation of
      the contributions of the levels of the factors to the inertia explained by each
      axis, the squared cosine of each factor level and the re-evaluation of the
      inertia explained by each axis have been added in order to improve the
      interpretations of the results of the decomposition.

PMID- 15975691
TI  - Implementing hygiene monitoring systems in hospital laundries in order to reduce
      microbial contamination of hospital textiles.
AB  - As textiles sent to hospital laundries contain many types of pathogenic
      organisms, it is important that laundering not only has an appropriate cleaning
      effect but also has a satisfactory disinfecting effect. Critical to this process
      is the maintenance of an appropriate hygiene level in the clean area of laundries
      in order to prevent recontamination of textiles from manual handling when
      ironing, folding, packing etc. The aims of this study were to evaluate the
      hygienic state of a hospital laundry, to introduce continuous sanitary measures,
      and to introduce a continuous hygiene monitoring system with an infection control
      programme. Two systems for evaluating hospital laundry hygiene were combined:
      HACCP principles (hazard analysis and critical control points) and RAL-GZ 992
      standards (quality assurance standard for textile care of hospital laundry).
      Evaluation of the hygienic state of the hospital laundry was carried out by
      evaluating the number and types of micro-organisms present at the critical
      control points throughout the whole laundering process, using RODAC agar plates
      for surface sampling and the pour plate method for investigating water samples.
      The initial examination showed that the sanitary condition of the laundry did not
      reach the required hygiene level. Therefore, fundamental sanitation measures were
      instituted and the examination was repeated. Results were then satisfactory. The
      most important critical control point was the chemothermal laundering efficiency
      of the laundering process. To prevent micro-organisms spreading into the entire
      clean working area, it is important that, in addition to regular sanitary
      measures such as cleaning/disinfecting all working areas, technical equipment and
      storage shelves etc., regular education sessions for laundry employees on proper
      hand hygiene is undertaken and effective separation of the clean and dirty
      working areas is achieved.

PMID- 15975692
TI  - [Botulinum toxin in neurology].

PMID- 15975693
TI  - [Pyogenic splenic abscesses. A review of 8 cases].
AB  - PURPOSE: Pyogenic splenic abscess is un uncommon and potentially life-threatening
      disease. Due to inconspicuous and nonspecific clinical picture, it remains a
      diagnostic challenge. Medical imaging progresses are helpful for diagnosis and
      treatment. METHODS: We tried to establish epidemiologic and clinical features and
      therapeutic possibilities of 8 cases of splenic abscesses occurred between 1993
      and 2002. RESULTS: There were 5 male patients and 3 female patients. Aged ranged
      from 17 to 53 years, with a median of 34 years. One patient was immunocompromised
      (colonic carcinoma). Common clinical presentations included fever (n=8) and left
      upper quadrant abdominal pain (n=7). Positive blood cultures were found in only
      four patients (50%) : Staphylococcus aureus (3) and coagulase negative
      Staphylococcus (1). Staphylococcus aureus and Bacteroides fragilis were isolated
      in one abscess pus respectively. The diagnosis was obtained by ultrasonography in
      all 8 cases. Antibiotics were prescribed in all cases for a mean length of 60
      days (30 - 110 days). Splenectomy and percutaneous CT-guided drainage were
      performed in one case respectively. Evolution was good in all cases. CONCLUSION:
      Splenic abscesses are increasingly recognized. The combination of clinical
      features and imaging findings, early diagnosis and treatment can be made.

PMID- 15975694
TI  - Bioelectric impedance and individual characteristics as prognostic factors for
      post-operative complications.
AB  - BACKGROUND AND AIMS: Malnutrition increases morbidity and mortality in surgical
      patients, and for this reason, several nutritional markers have been used as
      prognostic tools to identify surgical patients under a higher risk to develop
      complications in post-operative period. Few studies show the impact of
      nutritional markers after controlling for others variables, such as age and
      severity of disease. A new method, bioelectric impedance analysis (BIA), and its
      parameter, phase angle, have been described as a prognostic tool in several
      clinical situations, but they have never been studied in surgical population. The
      objective of this work is to assess the importance of nutritional variables and
      parameters from BIA as predictors of post-operative complications in a
      multivariable regression model. METHODS: The nutritional status of 225 adult
      patients scheduled to undergo gastrointestinal surgery was assessed by several
      methods, including bioelectric impedance analysis and subjective global
      assessment. Potential confounding factors were also studied. Patients were
      screened for post-operative complications until hospital discharge. RESULTS:
      Weight loss greater than 10%, subjective global assessment, nutritional risk
      assessment, ECM/BCM ratio and phase angle (from BIA) were the prognostic factors
      significantly associated with post-operative complications in the crude analysis.
      After adjusting for sex, age, marital status, tumors and pre-operative
      infections, only phase angle remained as a prognostic factor (RR=4.3; CI95% 1.6
      11.8 for phase angle <-0.8 sd), while the other nutritional variables lost their
      association with post-operative complications. CONCLUSION: Phase angle remains as
      an important prognostic factor for postoperative complications, even after
      adjusting for other individual predictors and confounders. Its utility in the
      identification of patients eligible for nutritional therapy has now to be
      evaluated.

PMID- 15975695
TI  - Model testing using data on 131I released from Hanford.
AB  - The Hanford test scenario described an accidental release of 131I to the
      environment from the Hanford Purex Chemical Separations Plant in September 1963.
      Based on monitoring data collected after the release, this scenario was used by
      the Dose Reconstruction Working Group of BIOMASS to test models typically used in
      dose reconstructions. The primary exposure pathway in terms of contribution to
      human doses was ingestion of contaminated milk and vegetables. Predicted mean
      doses to the thyroid of reference individuals from ingestion of 131I ranged from
      0.0001 to 0.8 mSv. For one location, predicted doses to the thyroids of two
      children with high milk consumption ranged from 0.006 to 2 mSv. The predicted
      deposition at any given location varied among participants by a factor of 5-80.
      The exercise provided an opportunity for comparison of assessment methods and
      conceptual approaches, testing model predictions against measurements, and
      identifying the most important contributors to uncertainty in the assessment
      result. Key factors affecting predictions included the approach to handling
      incomplete data, interpretation of input information, selection of parameter
      values, adjustment of models for site-specific conditions, and treatment of
      uncertainties.

PMID- 15975696
TI  - An algorithm for estimation of shoulder muscle forces for clinical use.
AB  - BACKGROUND: The shoulder joint represents an indeterminate mechanical system,
      making it difficult to predict individual muscle forces required to equilibrate a
      given arbitrary external force. Although considerable work has been published on
      this matter, no model exhibits the adaptability required for the analysis
      involving different positions of the humerus and for any external load. An
      algorithm involving decision-making loops is developed to predict forces exerted
      by muscles that cross the shoulder joint in equilibrating a given external force
      acting in an arbitrary direction, with the humerus in any one of 12 selected
      positions. METHODS: Muscle lever arms and directions of action collected from a
      full-size epoxy model of the shoulder joint are used together with the external
      force as input. The algorithm selects an appropriate group of muscles and step by
      step attributes small force increments to withstand the external moment while
      aiming at minimising the forces involved. Each muscle force increment is stored
      after every loop and eventually summed up. Stability of the glenohumeral joint is
      the final determining factor. FINDINGS: Six worked-out examples show interesting
      features of probable muscular activity. Muscle segmentation is of paramount
      importance for spatial control. Although stability can be achieved by increasing
      the overall rotator cuff activity (co-contraction), this is rarely necessary.
      INTERPRETATION: The strategy of force sharing among the muscles opens up the
      possibility to examine the outcome of muscle deficiencies and to investigate
      causes of joint instability as encountered in clinical practice. Further
      validation of the model is still needed, but certain clinical observations can be
      explained.

PMID- 15975697
TI  - Intrinsic and imposed hamstring length influence posterior pelvic rotation during
      hip flexion.
AB  - BACKGROUND: The contribution of posterior tilt of the pelvis (pelvic rotation) to
      hip flexion has been described for individuals who are standing, supine, and
      suspended. The effects of intrinsic and imposed hamstring length on the motion
      have not been investigated in a controlled manner. This study investigated the
      influence of intrinsic and imposed hamstring length on pelvic rotation during
      bilateral active hip flexion. METHODS: Intrinsic hamstring length was
      characterized by the maximal active straight leg raise angle. Hamstring length
      was imposed by immobilizing the knees in 0 degrees, 45 degrees, and 90 degrees of
      flexion. Pelvic and thigh segments were marked with reflective spheres. Subjects'
      saggital plane motion was captured using computerized motion analysis during
      bilateral hip flexion while both knees were immobilized in three positions.
      Multifactorial analysis of variance was employed to show the effect of intrinsic
      and imposed hamstring length on pelvic rotation. FINDINGS: Pelvic rotation
      occurred throughout the hip flexion range of motion. Pelvic rotation was
      influenced significantly by hip flexion angle, knee position, the interaction
      between hip flexion angle and knee position, and the interaction between hip
      flexion angle, knee position, and active straight leg raise angle.
      INTERPRETATION: Both intrinsic and imposed hamstring length influence pelvic
      rotation during bilateral hip flexion. These influences should be considered by
      clinicians who have individuals engage in hip flexion maneuvers.

PMID- 15975698
TI  - Changes in three dimensional lumbo-pelvic kinematics and trunk muscle activity
      with speed and mode of locomotion.
AB  - BACKGROUND: Control of the trunk is critical for locomotor efficiency. However,
      investigations of trunk muscle activity and three-dimensional lumbo-pelvic
      kinematics during walking and running remain scarce. METHODS: Gait parameters and
      three-dimensional lumbo-pelvic kinematics were recorded in seven subjects.
      Electromyography recordings of abdominal and paraspinal muscles were made using
      fine-wire and surface electrodes as subjects walked on a treadmill at 1 and 2 ms(
      1) and ran at 2, 3, 4 and 5 ms(-1). FINDINGS: Kinematic data indicate that the
      amplitude but not timing of lumbo-pelvic motion changes with locomotor speed.
      Conversely, a change in locomotor mode is associated with temporal but not
      spatial adaptation in neuromotor strategy. That is, peak transverse plane lumbo
      pelvic rotation occurs at foot strike during walking but prior to foot strike
      during running. Despite this temporal change, there is a strong correlation
      between the amplitude of transverse plane lumbo-pelvic rotation and stride length
      during walking and running. In addition, lumbo-pelvic motion was asymmetrical
      during all locomotor tasks. Trunk muscle electromyography occurred biphasically
      in association with foot strike. Transversus abdominis was tonically active with
      biphasic modulation. Consistent with the kinematic data, electromyography
      activity of the abdominal muscles and the superficial fibres of multifidus
      increased with locomotor speed, and timing of peak activity of superficial
      multifidus and obliquus externus abdominis was modified in association with the
      temporal adaptation in lumbo-pelvic motion with changes in locomotor mode.
      INTERPRETATION: These data provide evidence of the association between lumbo
      pelvic motion and trunk muscle activity during locomotion at different speeds and
      modes.

PMID- 15975699
TI  - Smoking and panic attacks, panic disorder, and agoraphobia: a review of the
      empirical literature.
AB  - The empirical literature regarding panic-spectrum problems (i.e., panic attacks,
      panic disorder, and agoraphobia) and cigarette smoking is reviewed. In the first
      section of the paper, empirical studies that document the prevalence of smoking
      and panic-related problems are presented and discussed. In the second section of
      the paper, studies pertaining to the role cigarette smoking may play in the onset
      and maintenance of panic-related problems are critically reviewed. In the third
      section of the paper, studies related to the association between panic
      vulnerability factors and the nature of smoking behavior are presented. In the
      fourth section of the paper, specific areas not otherwise covered in the review
      are presented to stimulate further development in these areas (e.g., specialized
      treatment development).

PMID- 15975700
TI  - The nature and severity of cognitive impairment associated with adjuvant
      chemotherapy in women with breast cancer: a meta-analysis of the current
      literature.
AB  - OBJECTIVE: Several studies have identified that adjuvant chemotherapy for breast
      cancer is associated with cognitive impairment; however, the magnitude of this
      impairment is unclear. This study assessed the severity and nature of cognitive
      impairment associated with adjuvant chemotherapy by conducting a meta-analysis of
      the published literature to date. METHOD: Six studies (five cross-sectional and
      one prospective) meeting the inclusion criteria provided a total of 208 breast
      cancer patients who had undergone adjuvant chemotherapy, 122 control participants
      and 122 effect sizes (Cohen's d) falling into six cognitive domains. First, the
      mean of all the effect sizes within each cognitive domain was calculated
      (separately for cross-sectional and prospective studies); second, a mean effect
      size was calculated for all of the effect sizes in each cross-sectional study;
      and third, regression analyses were conducted to determine any relationships
      between effect size for each study and four different variables. RESULTS: For the
      cross-sectional studies, each of the cognitive domains assessed (besides
      attention) showed small to moderate effect sizes (-0.18 to -0.51). The effect
      sizes for each study were small to moderate (-0.07 to -0.50) and regression
      analysis detected a significant negative logarithmic relationship (R2 = .63)
      between study effect size and the time since last receiving chemotherapy. For the
      prospective study, effect sizes ranged from small to large (0.11-1.09) and
      indicated improvements in cognitive function from the beginning of chemotherapy
      treatment to 3 weeks and even 1 year following treatment. CONCLUSION: This meta
      analysis suggests that cognitive impairment occurs reliably in women who have
      undergone adjuvant chemotherapy for breast cancer but that the magnitude of this
      impairment depends on the type of design that was used (i.e., cross-sectional or
      prospective). Thus, more prospective studies are required before definite
      conclusions about the effects of adjuvant chemotherapy on cognition can be made.

PMID- 15975701
TI  - Antidepressant-elicited changes in gene expression: remodeling of neuronal
      circuits as a new hypothesis for drug efficacy.
AB  - Although antidepressants have been used clinically for more than 50 years, no
      consensus has been reached concerning their precise molecular mechanism of
      action. Pharmacogenomics is a powerful tool that can be used to identify genes
      affected by antidepressants or by other effective therapeutic manipulations.
      Using this tool, others and we have identified as candidate molecular targets
      several genes or expressed sequence tags (ESTs) that are induced by chronic
      antidepressant treatment. In this article, we review antidepressant-elicited
      changes in gene expression, focusing especially on the remodeling of neuronal
      circuits that results. This refocusing motivates our hypothesis that this
      plasticity represents the mechanism for drug efficacy, and thus a causal event
      for clinical improvement. Defining the roles of these molecules in drug-induced
      neural plasticity is likely to transform the course of research on the biological
      basis of antidepressants. Such detailed knowledge will have profound effects on
      the diagnosis, prevention, and treatment of depression. Consideration of novel
      biological approaches beyond the "monoamine hypothesis" of depression is expected
      to evoke paradigm shifts in the future of antidepressant research.

PMID- 15975702
TI  - Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the
      population of Santiago (Chile) using a Total Diet Study.
AB  - Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the
      population of Santiago (Chile) was determined using a Total Diet Study in the
      market basket modality. After conducting a survey of the foods consumed in the
      last 24 h, the most consumed food products were included in the basket.
      Subsequently, they were cooked or prepared according to typical Chilean
      procedures and grouped into 17 food categories according to their chemical
      characteristics. The fish and shellfish group had the highest contents of As
      (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the
      sugar group had the highest content of Pb (251 ng/g ww). For a person with a body
      weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day),
      Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional
      tolerable weekly intake values established by the FAO/WHO. Consequently, the
      total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits
      estimated as safe.

PMID- 15975703
TI  - Implications for human health of the extensive bisphenol A literature showing
      adverse effects at low doses: a response to attempts to mislead the public.

PMID- 15975704
TI  - Social interactions and resource ownership in two private protected areas of
      Paraguay.
AB  - This paper describes the results of field research to dissect how social
      interactions differ between two reserves in Paraguay having very different styles
      of governance. The two reserves were Mbaracayu Natural Forest Reserve (Reserva
      Natural del Bosque de Mbaracayu, RNBM) and San Rafael Managed Resource Reserve
      (Reserva de Recursos Manejados San Rafael, RRMSR). RNBM is a private reserve
      owned by a non-governmental organisation, while RRMSR is a publicly-managed
      reserve, albeit with a substantial degree of private land ownership. Both
      reserves are intended to protect Atlantic Forest, one of the five world
      biodiversity 'hotspots', and also one of the most highly threatened. Each reserve
      and its buffer zone comprises a set of stakeholders, including indigenous
      communities and farmers, and the paper explores the interactions between these
      and the management regime. Indeed, while the management regimes of the two
      reserves are different, one being highly top-down (RNBM) and the other more
      socially inclusive (RRMSR), the issues that they have to deal with are much the
      same. However, while both management regimes will readily acknowledge the need to
      address poverty, inequality appears to be a far more sensitive issue. Whereas
      this may be expected for the privately-owned RNBM it is perhaps more surprising
      in RRMSR even when allowing for the fact that much of the land in the latter is
      in private hands. It is argued that the origins of this sensitivity rest within
      the broader features of Paraguayan society, and the prevalence of private land
      ownership. Yet ironically, it is the inequality in land ownership that is perhaps
      the most significant threat to conservation in both reserves. Therefore, while
      reserve-level analyses can provide some insight into the driving forces at play
      in the interaction between conservation and sustainable management, larger scales
      may be necessary to gain a fuller appreciation of the dynamics operating at site
      level. Even in a society with a history of centralised control these dynamics may
      be surprising.

PMID- 15975705
TI  - Molecular mechanisms of the neural melanocortin receptor dysfunction in severe
      early onset obesity.
AB  - The neural melanocortin receptors, melanocortin-3 and -4 receptors (MC3R and
      MC4R), have been shown to regulate different aspects of energy homeostasis in
      rodents. Human genetic studies showed that mutations in the MC4R gene are the
      most common monogenic form of obesity. Functional analyses of the mutant
      receptors revealed multiple defects. A classification scheme is presented for
      cataloguing the ever-increasing array of MC4R mutations. Functional analysis of
      the only inactivating MC3R mutation is also summarized. Insights from the
      analyses of the naturally occurring mutations in the MC3R and MC4R on the
      structure and function of these receptors are highlighted.

PMID- 15975706
TI  - Mechanisms of bone invasion and metastasis in human neuroblastoma.
AB  - Bone is the second most common site of metastasis in neuroblastoma. Over the last
      several years, our understanding of the mechanism of bone metastasis in
      neuroblastoma has significantly improved. Like breast cancer and myeloma,
      neuroblastoma cells activate osteoclasts to form osteolytic lesions. Activation
      occurs via the receptor activator of NFkappaB ligand (RANKL) or in the absence of
      RANKL via activation of bone marrow mesenchymal stem cells and stimulation by
      these cells of the expression of IL-6, a potent osteoclast activating factor.
      Several targets for therapeutic intervention can now be identified. Inhibition of
      osteoclast activation by bisphosphonates has already shown to be effective in
      preclinical models of neuroblastoma bone metastasis and should now be tested in
      phase I clinical studies. Inhibition of RANKL and IL-6 are other potential
      targets that require preclinical studies before being tested in patients. This
      article provides a review of our current understanding of the mechanisms involved
      in bone metastasis in neuroblastoma and discusses how this knowledge is leading
      to the identification of new targets for therapeutic intervention.

PMID- 15975707
TI  - The tea polyphenols EGCG and EGC repress mRNA expression of human telomerase
      reverse transcriptase (hTERT) in carcinoma cells.
AB  - Tea polyphenols have inhibitive effects for carcinogenesis. A reporter system
      controlled by hTERT promoter was constructed to evaluate the effects of tea
      polyphenols, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC)
      on the repression of hTERT transcription. The hTERT promoter activity was
      selectively repressed by 20-40 microM EGCG and EGC in a dose- and time-dependent
      manner. Real-time RT-PCR confirmed that the endogenous hTERT mRNA level was
      decreased in H1299, OECM-1 and SAS cells treated with EGCG or EGC. Our results
      identified the repression activities of EGCG and EGC toward telomerase expression
      that might be linked to inhibition of carcinoma cell growth. This cell-based
      reporter system is useful for screening drugs targeting hTERT repression.

PMID- 15975708
TI  - NSAIDs in neuroblastoma therapy.
AB  - Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to
      prostaglandins. COX-2 is upregulated in several adult epithelial cancers. In
      neuroblastoma it has been shown that the majority of primary tumours and cell
      lines express high levels of COX-2, whereas normal adrenal medullas from children
      do not express COX-2. Treatment of neuroblastoma cells with nonsteroidal anti
      inflammatory drugs (NSAIDs), inhibitors of COX, induces caspase-dependent
      apoptosis via the intrinsic mitochondrial pathway. Established neuroblastoma
      xenografts in nude rats treated with the dual COX-1/COX-2 inhibitor, diclofenac,
      or the COX-2 specific inhibitor, celecoxib significantly inhibits neuroblastoma
      growth in vivo. In vitro, arachidonic acid and diclofenac synergistically induces
      neuroblastoma cell death. This effect is further pronounced when lipoxygenases is
      inhibited simultaneously. Proton MR-spectroscopy (1H MRS) of neuroblastoma cells
      treated with COX-inhibitors demonstrates accumulation of polyunsaturated fatty
      acids and depletion of choline compounds. Thus, 1H MRS, which can be performed
      with clinical MR-scanners, is likely to provide pharmacodynamic markers of
      neuroblastoma response to COX-inhibition. Taken together, these data suggest the
      use of NSAIDs as a novel adjuvant therapy for children with neuroblastoma.

PMID- 15975709
TI  - Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited
      an inhibitory effect on the migration and invasion of a human lung cancer cell
      line.
AB  - Anthocyanins, present in various fruits and vegetables as natural colorant, have
      been well characterized to be involved in various bioactive properties and are
      wildly used for their antioxidant properties. Furthermore, recent studies have
      revealed pleiotropic anticancer and antiproliferative capabilities of
      anthocyanin. Berry extract contains high amounts of anthocyanins and is commonly
      used in diet or in some therapeutic applications. In this study, we first
      observed that cyanidin 3-rutinoside and cyanidin 3-glucoside (extracted from
      Morus alba L.) exerted a dose-dependent inhibitory effect on the migration and
      invasion, of highly metastatic A549 human lung carcinoma cells in absence of
      cytotoxicity. The results showed that cyanidin 3-glucoside and cyanidin 3
      rutinoside treatments could decrease the expressions of matrix matalloprotinase-2
      (MMP-2) and urokinase-plasminogen activator (u-PA) in a dose-dependent manner and
      enhance the expression of tissue inhibitor of matrix matalloprotinase-2 (TIMP-2)
      and plasminogen activator inhibitor (PAI). Further analysis with semi
      quantitative RT-PCR showed that these alterations were all on the transcriptional
      level. Further, a treatment of cyanidin 3-rutinoside and cyanidin 3-glucoside
      also resulted in an inhibition on the activation of c-Jun and NF-kappaB.
      Together, these result suggested that anthocyanins could decrease the in vitro
      invasiveness of cancer cells and therefore, may be of great value in developing a
      potential cancer therapy.

PMID- 15975710
TI  - Epidural compression in neuroblastoma: Diagnostic and therapeutic aspects.
AB  - The involvement by tumour of intervertebral foramina and the consequent invasion
      of the spinal space, accompanied or not by neurological symptoms, represent a
      well-recognised pattern of presentation of neuroblastoma. The main peculiarity of
      this condition stands in the fact that, in case of its late detection or
      inadequate treatment, severe, permanent neurological compromise may ensue.
      Surprisingly enough, remarkable disagreements still exist regarding its optimal
      treatment and the related literature provide contrasting indications at this
      respect. The neurosurgical and the chemotherapeutic approaches have equally
      convinced supporters, while the use of radiation therapy is uncommon, possibly
      without good reasons. This mini-review intends to report the clinical experiences
      of the major Paediatric Oncology Groups with the aim to collect as many data as
      possible in the perspective of establishing common guidelines for proper
      diagnosing and treatment of this important complication.

PMID- 15975711
TI  - BRCA1 regulation of transcription.
AB  - BRCA1, a tumor suppressor gene on chromosome 17q21, was identified in 1994 based
      on its linkage to hereditary breast and ovarian cancer syndromes. The BRCA1 gene
      encodes a 220 kDa nuclear phosphoprotein. Studies aimed at elucidating the
      mechanisms of its tumor suppressor activity have revealed, in part, that BRCA1
      participates in the DNA damage response and acts to maintain the integrity of the
      genome. This activity is generic and does not account for the propensity of BRCA1
      mutation carriers to develop specific tumor types rather than a broad spectrum of
      cancers. In addition to genome maintenance, BRCA1 has been found to broadly
      regulate gene transcription, even though it is not itself a sequence-specific DNA
      binding transcription factor. The ability of BRCA1 to function as a coregulator
      of transcription may underlie some of its tumor suppressor activity and may
      explain the tissue-specific nature of this activity. This review will focus on
      how BRCA1 selectively regulates transcription and how this regulatory function
      may relate to tumor suppression.

PMID- 15975712
TI  - Application of an effective method in predicting breakthrough curves of fixed-bed
      adsorption onto resin adsorbent.
AB  - Removal of many organic pollutants including phenolic compounds from industrial
      wastewater can always be achieved by fixed-bed adsorption onto the polymeric
      resin adsorbent, and the relevant breakthrough curves would provide much valuable
      information to help to design a fixed-bed adsorption process in field
      application. In the present study, a model developed based on the constant
      pattern wave approach theory and the Freundlich model was adopted to describe the
      breakthrough curves of phenol and p-nitrophenol adsorption onto a macroreticular
      resin adsorbent NDA-100 from aqueous solution. Column experiments were performed
      at different conditions to verify the model and the results proved that the model
      would describe the breakthrough curves well. Effect of the operation parameters
      on breakthrough curves was also discussed to get helpful information in choosing
      the adsorption process.

PMID- 15975713
TI  - Anorexigenic action of pituitary adenylate cyclase-activating polypeptide (PACAP)
      in the goldfish: feeding-induced changes in the expression of mRNAs for PACAP and
      its receptors in the brain, and locomotor response to central injection.
AB  - Our recent research has indicated that intracerebroventricular (ICV)
      administration of pituitary adenylate cyclase-activating polypeptide (PACAP)
      suppresses food intake in the goldfish. We therefore examined feeding- and
      fasting-induced changes in the expression of mRNAs for PACAP and its receptors in
      the goldfish brain, and the effect of ICV administration of synthetic PACAP on
      locomotor activity in the goldfish. Semiquantitative analysis revealed that the
      expression of mRNAs for PACAP and the PAC1 receptor was significantly increased
      by excessive feeding (daily food supply at >or=5% of the body weight [BW]) for 7
      days. ICV administration of PACAP at 20 pmol/g BW induced a significant decrease
      in locomotor activity during the 60-min post-treatment observation period. These
      results suggest that PACAP may have an anorexigenic action via hypomotility in
      goldfish.

PMID- 15975714
TI  - Ketogenic diet reduces hypoglycemia-induced neuronal death in young rats.
AB  - Hypoglycemia is an important complication of insulin treatment in diabetic
      children and may contribute to lasting cognitive impairment. Previous studies
      demonstrated that 21-day-old rats (P21) subjected to brief, repetitive episodes
      of hypoglycemia sustain cortical neuronal death. The developing brain is capable
      of utilizing alternative energy substrates acetoacetate and beta-hydroxybutyrate.
      In these studies we tested the hypothesis that the developing brain adapted to
      ketone utilization and provided with ketones during hypoglycemia by eating a
      ketogenic diet would sustain less brain injury compared to littermates fed a
      standard diet. Supporting this hypothesis, P21 rats weaned to a ketogenic diet
      and subjected to insulin-induced hypoglycemia at P25 had significantly less
      neuronal death than rats on a standard diet. This animal model may provide
      insight into the determinants influencing the brain's susceptibility to
      hypoglycemic injury.

PMID- 15975715
TI  - Defect in normal developmental increase of the brain biogenic amine
      concentrations in the mecp2-null mouse.
AB  - To clarify whether Mecp2 dysfunction may cause impairment of the monoaminergic
      and serotonergic systems, we measured the whole brain concentrations of biogenic
      amines and related substrates in three mecp2-null male mice and four control mice
      of each age at 0-42 postnatal days by HPLC methods. After 14 postnatal days,
      concentrations of biogenic amines were smaller in mecp2-null mice than those in
      control mice and at 42 postnatal days, norepinephrine, dopamine and serotonin
      concentrations in mecp2-null mice were significantly smaller by 25, 24 and 16%,
      respectively. This result suggested that the absence of Mecp2 does not impair the
      neurogenesis of monoaminergic and serotonergic neurons but causes succeeding
      impairment of those neuronal systems from 14 postnatal days.

PMID- 15975716
TI  - Spinal glial glutamate transporters downregulate in rats with taxol-induced
      hyperalgesia.
AB  - Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were
      examined in the spinal cord of rats with chemotherapy (taxol)-induced mechanical
      hyperalgesia. Immunohistochemical studies show that the expression of both GLAST
      and GLT-1 in the L4-L5 spinal dorsal horn is decreased by 24% (P<0.001) and 23%
      (P<0.001), respectively, in rats with taxol-induced hyperalgesia as compared with
      those in control rats. These changes were further confirmed using an enzyme
      linked immunosorbent assay that confirmed downregulation of GLAST by 36% (P<0.05)
      and GLT-1 by 18% (P<0.05) in the L4-L5 spinal cord of taxol-treated rats. These
      data indicate that downregulation of glutamate transporters may contribute to the
      development of hyperalgesia induced by taxol and suggest that glutamate
      transporters may be a new target for treatment of pain.

PMID- 15975717
TI  - Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a
      sample of herding breed dogs living in Australia.
AB  - A study was performed to determine the frequency of the mutant MDR1 allele
      associated with ivermectin sensitivity in a sample of Collies and other herding
      breeds living in Australia. Buccal swab samples were collected from 33 Collies,
      17 Australian Shepherds, 7 Border Collies and 7 Shelties for determination of
      MDR1 genotype. DNA was extracted and the polymerase chain reaction was performed
      to amplify a 148 base pair (wildtype MDR1 genotype or 144 base pair (mutant MDR1
      genotype) amplicon containing the MDR1 mutation. Sequence analysis was performed
      to determine the genotype of each dog. Adequate quantities of DNA for unequivocal
      genotyping were obtained from 61 of 64 samples. The previously described MDR1
      mutation was identified in Collies, Australian Shepherds and Shelties living in
      Australia, but not in Border Collies (although sample numbers were low). Twelve
      percent (4/33) of the Collies studied were homozygous for the normal allele
      (normal), 64% (21/33) were heterozygous (carrier) and 24% (8/33) were homozygous
      for the mutant allele (affected). Results of this study indicate that a high
      percentage of herding breeds presenting to veterinarians in Australia harbor the
      MDR1 mutation, thus impacting some therapeutic decisions.

PMID- 15975718
TI  - Importance of Lutzomyia longipalpis in the dynamics of transmission of canine
      visceral leishmaniasis in the endemic area of Porteirinha Municipality, Minas
      Gerais, Brazil.
AB  - A study of Lutzomyia longipalpis (Lutz and Neiva, 1912) (Diptera: Psychodidae),
      the primary vector of American visceral leishmaniasis (AVL), and the canine form
      of the disease, was carried out in Porteirinha. The city is situated in the
      northern part of the Brazilian State of Minas Gerais and is an endemic area of
      AVL. Systematic phlebotomine captures were performed in seven districts with
      previously reported cases of canine visceral leishmaniasis, during 2 years
      (January 2000--December 2001). A total of 2328 specimens of L. longipalpis were
      captured. The association between the local climate variables and the population
      density of L. longipalpis was evaluated and rainfall was determined to be a major
      factor, with increased populations during the rainy season (October--March). At
      the same time period, blood samples from every dog domiciled in the same seven
      districts, in total 14,077 animals, were analyzed for infection by viscerotropic
      Leishmania using indirect immunofluorescence assay (IFA). Accumulated incidence
      rates of canine VL per district varied from 3.40 to 14.34 for the 2-year period.
      A positive correlation between the population density of L. longipalpis and the
      canine cases of visceral leishmaniasis in Porteirinha was observed.

PMID- 15975719
TI  - Assembly of the full-length recombinant mouse prion protein I. Formation of
      soluble oligomers.
AB  - The conversion of a monomeric alpha-helix-rich isoform to multimeric beta-sheet
      rich isoforms is a prominent feature of the conversion between PrP(C) and
      PrP(SC). We mimicked this process in vitro by exposing an unglycosylated
      recombinant form of the full-length mouse prion protein ((Mo)PrP(23-231)) to an
      acidic pH, at 37 degrees C, and we monitored the kinetics of conformational
      change and assembly. In these conditions, monomeric (Mo)PrP(23-231) converts
      slowly to two ensembles of soluble oligomers that are separated by size exclusion
      chromatography. The larger oligomers (I) are unstable, and their formation
      involves almost no change in secondary structure content. The smaller oligomers
      (II) form stable spherical or annular particles containing between 8 and 15
      monomers as determined by multi-angle laser light scattering (MALLS). Their
      formation is concomitant with the main, thought limited, change in the secondary
      structure content (10%) seen by Fourier Transform Infrared (FTIR) spectroscopy.
      Even if these oligomers conserve a large part of the secondary structure of
      monomeric PrP, they exhibit amyloid features with the appearance of
      intermolecular beta-structure as revealed by the appearance of an IR band below
      1620 cm(-1).

PMID- 15975720
TI  - The risk factors for acquisition of imipenem-resistant Pseudomonas aeruginosa in
      the burn unit.
AB  - OBJECTIVE: This study was conducted to determine the risk factors for acquisition
      of imipenem-resistant Pseudomonas aeruginosa (IRPA) in the burn unit. METHODS:
      Patients hospitalized in the burn unit from July 2003 to November 2004 were
      included in this study. The features of patients with isolated IRPA were compared
      with those of patients with isolated imipenem-susceptible P. aeruginosa (ISPA).
      Demographic features, total burn surface area (TBSA), burn depth, antimicrobials
      used in 15-day period before isolation, and presence of IRPA in the unit at the
      same period were included in the risk factors analysis. RESULTS: P. aeruginosa
      was recovered from 133 patients in this period, 93 were IRPA and 40 were ISPA.
      There was no significant difference between patients with ISPA and patients with
      IRPA in terms of age, TBSA, and burn depth. In multivariate logistic regression
      analysis, hospital stay before isolation (odds ratio (OR): 3.6), carbapenem usage
      (OR: 7.4), broad-spectra antibiotic usage (OR: 6.5), previous presence of ISPA in
      the patient (OR: 1.7) and presence of IRPA in the unit at the same period (OR:
      2.6) were independent risk factors for acquisition of IRPA. CONCLUSION: Long
      hospitalization time, previous imipenem/meropenem use, previous broad-spectra
      antibiotic use, previous presence of ISPA in a patient and presence of IRPA in a
      unit at the same period were associated with acquisition of IRPA in the burn
      unit. In order to decrease the incidence of IRPA isolation, the usage of broad
      spectra antibiotics, especially carbapenem, should be restricted, hospitalization
      time should be shortened if possible, and universal isolation precautions should
      be strictly applied to prevention cross-contamination.

PMID- 15975721
TI  - Removal of inflammatory cytokines and endotoxin by veno-venous continuous renal
      replacement therapy for burned patients with sepsis.
AB  - OBJECTIVE: To evaluate the effect of veno-venous continuous renal replacement
      therapy (CRRT) on the plasma levels of endotoxin and cytokines in severely burned
      patients with sepsis. METHODS: Twenty adult severely burned patients with sepsis
      were studied. For the diagnosis of sepsis, patients were randomly divided into
      CRRT (n=10) and Control (n=10). Both groups received conventional therapy after
      admission. Veno-venous CRRT was administered to 10 patients in the CRRT group
      whenever patients were determined to be septic. The plasma level of endotoxin,
      TNF-alpha, IL-1 beta, IL-6 and IL-8 were measured at 0, 1, 2, 6, 12, 36 and 60 h
      after CRRT initiation, and at 0, 12, 36 and 60 h after the patients were
      diagnosed as having sepsis in the Control group. MAIN RESULTS: Plasma level of
      endotoxin and all the cytokines after CRRT initiation were significantly lower
      than those before the treatment (P<0.01). The serial change of endotoxin, IL-1
      beta, IL-6 and IL-8 was significantly lower at 12, 36 and 60 h after treatment
      compared with Control groups (P<0.01). A significant decrease in plasma TNF-alpha
      levels was seen at 36 and 60 h after treatment compared with Control groups
      (P<0.01). CONCLUSION: Plasma endotoxin and cytokines (TNF-alpha, IL-1 beta, IL-6
      and IL-8) can be removed effectively with CRRT in severely burned patients with
      sepsis.

PMID- 15975722
TI  - Local injection of a glutamate uptake inhibitor into the ventral tegmental area
      produces sensitization to the behavioural effects of d-amphetamine.
AB  - Circumstantial evidence suggests that sensitization to the behavioral effects of
      d-amphetamine is mediated by increased glutamate levels in the ventral tegmental
      area. To test this directly, the present study examined whether increasing
      glutamate levels in the ventral tegmental area with a glutamate uptake inhibitor
      is sufficient, in the absence of d-amphetamine administration, to elicit
      sensitization to a subsequent d-amphetamine challenge. Rats were treated
      bilaterally once a day for 2 days with either intra-ventral tegmental area L
      trans-pyrollidine-2,4-dicarboxylic acid (50 nmol), saline, L-trans-pyrollidine
      2,4-dicarboxylic acid coadministered with the competitive N-methyl-d-aspartate
      antagonist (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid; CPP, 0.5
      nmol), or CPP alone (0.5 nmol; all 1.0 microl/side). Following a 2 day withdrawal
      period, all rats were administered systemic d-amphetamine (1 mg/kg, i.p.).
      Repeated intra-ventral tegmental area injection of L-trans-pyrollidine-2,4
      dicarboxylic acid sensitized animals to the behavioral effects of a systemic d
      amphetamine challenge, an action which was blocked by co-administration of CPP.
      The results directly implicate ventral tegmental area glutamate in the process of
      sensitization to d-amphetamine. Furthermore, they demonstrate that inhibition of
      glutamate uptake produces the neuroadaptations necessary to induce sensitization,
      adding support to the contention that d-amphetamine sensitizes by modulating
      glutamate uptake.

PMID- 15975723
TI  - The inhibitor kappaB-ortholog Cactus is necessary for normal neuromuscular
      function in Drosophila melanogaster.
AB  - The Drosophila inhibitor-kappaB ortholog Cactus acts as an inhibitor of the Rel
      transcription factors Dorsal and Dif. In blastoderm cells and immune competent
      cells, Cactus inhibits Dorsal and Dif by preventing their nuclear localization.
      Cactus, Dorsal and Dif are also expressed in somatic muscles, where Cactus and
      Dorsal, but not Dif, are enriched at the neuromuscular junction. Mutations in
      dorsal cause neuromuscular defects and mislocalization of Cactus. Here, we
      investigated whether mutations in cactus affect the neuromuscular system and
      subcellular localization of Dorsal and Dif. Using locomotion assays, as well as
      physiological and immunochemical methods, we found that wild type Cactus is
      necessary for the normal function of the larval neuromuscular system. The
      phenotype comprises i) altered bouton numbers and impaired neurotransmitter
      release in the neuromuscular junctions in the abdominal segments, ii) muscular
      weakness and iii) poor locomotion performance, probably reflecting a general
      neuromuscular impairment. Interestingly, in cactus mutants the subcellular
      localization of Dorsal and Dif in muscle is not affected, whereas cactus protein
      is not detected in the nucleus. This suggests, together with the similarities
      between the phenotypes induced by cactus and dorsal mutations, that in larval
      muscles the function of Cactus might be cooperation to the transcriptional
      activity of Rel proteins more than their cytoplasmic retention. The similarities
      with inhibitor-kappaB/nuclear factor kappaB interactions and muscle pathology in
      mammals point to Drosophila as a suitable experimental system to clarify the
      complex interactions of these proteins in muscle postembryonic development and
      activity.

PMID- 15975724
TI  - Action of neuropeptide Y on nociceptive transmission in substantia gelatinosa of
      the adult rat spinal dorsal horn.
AB  - Effects of neuropeptide Y (NPY) on substantia gelatinosa neurons were
      investigated in adult rat spinal cord slices using blind whole-cell patch-clamp
      technique. Bath application of NPY (1 microM) induced a membrane
      hyperpolarization, resulting in a suppression of the dorsal root stimulation
      induced action potentials in 24% of the substantia gelatinosa neurons tested. In
      voltage clamp mode, NPY produced an outward current dose-dependently in about one
      third of substantia gelatinosa neurons at the holding potential of -60 mV, which
      was not affected by tetrodotoxin (1 microM). The NPY-induced current was
      suppressed by perfusion with a Ba2+-containing external solution and a Cs2SO4 or
      tetraethylammonium-containing pipette solution. In addition, The NPY-induced
      outward currents reversed its polarity near the equilibrium potential of K+ ions
      (-93 mV). The response to NPY recorded with guanosine-5'-O-(2-thiodiphosphate)
      beta-S (GDP-beta-S) containing pipette solution was abolished 30 min after patch
      formation, suggesting that the response was mediated by the G-protein-coupled
      receptors. Application of an NPY-Y1 selective agonist, [Leu(31), Pro(-34)]-NPY (1
      microM), for 30 s also induced an outward current with a similar time course and
      amplitude to that induced by NPY. On the other hand, the NPY response was blocked
      by a simultaneous application of NPY-Y1 selective antagonist, BIBP 3226 (1
      microM). No significant changes were found in amplitude and frequency of
      miniature excitatory postsynaptic currents and dorsal root evoked excitatory
      postsynaptic currents by NPY. In addition, NPY did not affect both of the
      miniature inhibitory postsynaptic currents and evoked inhibitory postsynaptic
      currents, mediated by either the GABA or glycine receptor. These findings, taken
      together, suggest that NPY produces an outward current in substantia gelatinosa
      neurons through G-protein coupled, and NPY-Y1 receptor-mediated activation of K+
      channels without affecting presynaptic components. The inhibition of the synaptic
      transmission from the primary fibers to the substantia gelatinosa neurons is
      considered to contribute to the antinociceptive effects of NPY.

PMID- 15975725
TI  - Dynamic response properties of visual neurons and context-dependent surround
      effects on receptive fields in the tectum of the salamander Plethodon shermani.
AB  - Neuronal responses to complex prey-like stimuli and rectangles were investigated
      in the tectum of the salamander Plethodon shermani using extracellular single
      cell recording. Cricket dummies differing in size, contrast or movement pattern
      or a rectangle were moved singly through the excitatory receptive field of a
      neuron. Paired presentations were performed, in which a reference stimulus was
      moved inside and the different cricket dummies or the rectangle outside the
      excitatory receptive field. Visual object recognition involves much more complex
      spatial and temporal processing than previously assumed in amphibians. This
      concerns significant changes in absolute number of spikes, temporal discharge
      pattern, and receptive field size. At single presentation of stimuli, the number
      of discharges was significantly changed compared with the reference stimulus, and
      in the majority of neurons the temporal pattern of discharges was changed in
      addition. At paired presentation of stimuli, neurons mainly revealed a
      significant decrease in average spike number and a reduction of excitatory
      receptive field size to presentation of the reference stimulus inside the
      excitatory receptive field, when a large-sized cricket stimulus or the rectangle
      was located outside the excitatory receptive field. This inhibition was
      significantly greater for the large-sized cricket stimulus than for the
      rectangle, and indicates the biological relevance of the prey-like stimulus in
      object selection. The response properties of tectal neurons at single or paired
      presentation of stimuli indicate that tectal neurons integrate information across
      a much larger part of visual space than covered by the excitatory receptive
      field. The spike number of a tectal neuron and the spatio-temporal extent of its
      excitatory receptive field are not fixed but depend on the context, i.e. the
      stimulus type and combination. This dynamic processing corresponds with the
      selection of the stimuli in the visual orienting behavior of Plethodon
      investigated in a previous study, and we assume that tectal processing is
      modulated by top down processes as well as feedback circuitries.

PMID- 15975726
TI  - Delta9-tetrahydrocannabinol increases C6 glioma cell death produced by oxidative
      stress.
AB  - (-)Delta9-tetrahydrocannabinol is a scavenger of free radicals. However, the
      activation of the CB1 receptor in cultured C6 glioma cells by (-)delta9
      tetrahydrocannabinol in the presence of reagents generating reactive oxygen
      species leads to amplification of the cellular damage from oxidative stress. This
      was evident by increased loss of cell wall integrity, impaired mitochondrial
      function and reduction of glucose uptake. In addition, (-)delta9
      tetrahydrocannabinol treatment was also found to be deleterious to the cells
      under conditions of glucose starvation. Free radicals have been implicated in
      various conditions leading to cell death and, as a routine, the Fenton reaction
      is utilized for modeling reactive oxygen species production. Our study was
      performed using a cell permeating Fe(III) chelating quinone that provides more
      physiological conditions for mimicking the naturally occurring oxidative stress
      within the cell and thus serves as a better model for natural reactive oxygen
      species formation.

PMID- 15975727
TI  - Autonomic brainstem nuclei are linked to the hippocampus.
AB  - Vagal nerve stimulation has been reported to enhance memory in both rats and
      humans, and to be an effective treatment for epilepsy in some patients, but the
      underlying neuroanatomical substrate(s) responsible for these effects remains
      unknown. Since there is no direct anatomical projection from the nucleus tractus
      solitarius, the main vagal relay site of the brain, to the hippocampus, we tested
      whether a multisynaptic pathway exists. Pseudorabies virus, a pig herpesvirus
      that can be used as a retrograde transneuronal tracer, was injected into the
      ventral CA1 hippocampus of rats, and after 4 days, pseudorabies virus infected
      neurons were identified in the general visceral portion of the nucleus tractus
      solitarius, with the majority being localized in the A2 noradrenergic cell group.
      Other autonomic brainstem nuclei, including the parabrachial nucleus, locus
      coeruleus, A1 and A5 noradrenergic cell groups, and C1 adrenergic cell group,
      were labeled. In order to identify some of the potential relay sites of the
      nucleus tractus solitarius-->hippocampal pathway, immunotoxin lesions of the
      ventral CA1 region were made that selectively destroyed either the noradrenergic
      or cholinergic fibers. After 2 weeks' recovery, pseudorabies virus was injected
      in this same CA1 area, and 4 days later, the transneuronal labeling in the
      nucleus tractus solitarius was reduced by approximately 65%. These findings
      suggest that the noradrenergic neurons of the locus coeruleus and cholinergic
      neurons of the medial septum/diagonal band are likely to be relay sites for this
      pathway. Other potential linkages are discussed. In summary, this is the first
      anatomical report to show that the general visceral region of nucleus tractus
      solitarius is linked via multisynaptic relays to the hippocampus.

PMID- 15975728
TI  - Transmitter content, origins and connections of axons in the spinal cord that
      possess the serotonin (5-hydroxytryptamine) 3 receptor.
AB  - Recent evidence suggests that serotonin has pronociceptive actions in the spinal
      cord when it acts through 5-hydroxytryptamine (5-HT)(3) receptors. Cells and axon
      terminals which are concentrated in the superficial dorsal horn possess this
      receptor. We performed a series of immunocytochemical studies with an antibody
      raised against the 5-HT(3A) subunit in order to address the following questions:
      1) Are axons that possess 5-HT(3) receptors excitatory? 2) Are 5-HT(3) receptors
      present on terminals of myelinated primary afferents? 3) What is the chemical
      nature of dorsal horn cells that possess 5-HT(3) receptors? 4) Do axons that
      possess 5-HT(3) receptors target lamina I projection cells? Approximately 45% of
      5-HT(3A) immunoreactive boutons were immunoreactive for the vesicular glutamate
      transporter 2 and almost 80% formed synapse-like associations with GluR2 subunits
      of the AMPA receptor therefore it is principally glutamatergic axons that possess
      the receptor. Immunoreactivity was not present on myelinated primary afferent
      axons labeled with the B-subunit of cholera toxin or those containing the
      vesicular glutamate transporter 1. Calbindin (which is associated with excitatory
      interneurons) was found in 44% of 5-HT(3A) immunoreactive cells but other markers
      for inhibitory and excitatory cells were not present. Lamina I projection cells
      that possessed the neurokinin-1 receptor were associated with 5-HT(3A) axons but
      the density of contacts on individual neurons varied considerably. The results
      suggest that 5-HT(3) receptors are present principally on terminals of excitatory
      axons, and at least some of these originate from dorsal horn interneurons. The
      relationship between lamina I projection cells and axons possessing the 5-HT(3)
      receptor indicates that this receptor has an important role in regulation of
      ascending nociceptive information.

PMID- 15975729
TI  - Frequency of recent cocaine and alcohol use affects drug craving and associated
      responses to stress and drug-related cues.
AB  - RATIONALE: Stress is known to increase drug craving, associated physiological
      arousal and risk of relapse in drug dependent individuals. However, it is unclear
      whether these responses are altered by recent frequency of drug use. The current
      study examined whether frequency of cocaine and alcohol abuse alters drug craving
      and associated arousal with laboratory exposure to stress and to drug related
      cues. METHODS: Fifty-four recently abstinent treatment-seeking cocaine abusers
      who were part of a study on stress and drug craving were categorized into high-
      and low-frequency users on the basis of their recent cocaine use. The high use
      cocaine group also consumed significantly more alcohol than the low use cocaine
      group. Participants were exposed to a brief 5-min guided imagery procedure that
      involved imagining a recent personal stressful situation, a personal drug-related
      situation and a neutral-relaxing situation, one imagery session on separate days
      presented in random order. Subjective (craving and anxiety), cardiovascular
      (heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP))
      and biochemical (adrenocorticotropic hormone (ACTH), cortisol, prolactin)
      measures were assessed. RESULTS: High-frequency abusers demonstrated a
      significantly greater drug craving, anxiety and associated cardiovascular and
      hypothalamic-pituitary-adrenal (HPA) response to both stress and drug-cue
      exposure as compared to low-frequency abusers. CONCLUSIONS: Increased frequency
      of recent cocaine and alcohol use is associated with an enhanced stress and cue
      induced drug craving and arousal response that appears to be similar to the
      effects of cocaine, and one that may increase the vulnerability to drug-seeking
      behavior and relapse in drug dependent individuals.

PMID- 15975730
TI  - Physiological correlates of cognitive functioning in an elderly population.
AB  - Cognitive decline in old age is not universal or inevitable. Associations have
      been observed with neuroendocrine function, but the relevance of other
      physiological processes is unclear. We predicted that impairment of memory in an
      ageing population would be related to the dysregulation of neuroendocrine and
      cardiovascular responses. One hundred and thirty-nine participants (65-80 years)
      were recruited from general practice in London. Two standardised verbal paired
      associates recall tasks were administered in order to determine declarative
      memory performance, and a fluid intelligence task (matrix reasoning) was also
      performed. Salivary cortisol samples were collected every 10 min, while blood
      pressure and heart rate were measured before, during and after each task. Illness
      history and medication use were obtained from medical records. Multiple linear
      regression analysis, adjusted for age, gender, education, chronic illness, and
      medication use, revealed that cortisol responses were inversely related to memory
      performance. Additionally, superior memory was associated with more effective
      post-task recovery of heart rate (in both men and women) and diastolic blood
      pressure recovery in men. Cardiovascular recovery effects were independent of
      covariates, and of levels of heart rate and blood pressure measured during tasks
      themselves. These associations were also independent of subjective ratings of
      stress and perceived performance. Neither neuroendocrine nor cardiovascular
      responses were related to performance of the reasoning task. We conclude that
      memory in the elderly is associated both with hypothalamic-pituitary
      adrenocortical function and cardiovascular regulation. Disturbances of
      neuroendocrine and hemodynamic function may be related to greater vulnerability
      to cognitive decline.

PMID- 15975731
TI  - Do predisposing and family background characteristics modify or confound the
      relationship between drinking frequency and alcohol-related aggression? A study
      of late adolescent and young adult drinkers.
AB  - The present study examined whether predisposing and family background
      characteristics confounded (common cause/general deviance theory) or modified
      (conditional/interactive theory) the association between drinking frequency and
      alcohol-related aggression. A secondary analysis of the US National Longitudinal
      Survey of Youth was conducted using a composite sample of drinkers, ages 17 to
      21, from the 1994, 1996, and 1998 Young Adult surveys (n=602). No evidence of
      confounding of the relationship between drinking frequency and alcohol-related
      aggression was found. In addition, predisposing characteristics did not modify
      the association between drinking frequency and alcohol-related aggression.
      However, family background variables (mother's education and any poverty) were
      important explanatory variables for alcohol-related aggression among males,
      whereas recent aggression (fights at school or work) was an important predictor
      for females. Overall, lack of support for the conditional/interactive and common
      cause theories of the alcohol and aggression relationship suggests that alcohol
      has an independent explanatory role in alcohol-related aggression. In addition,
      the gender differences found in the present study highlight the need for more
      gender-focussed research on predictors of alcohol-related aggression, especially
      among adolescents and young adults.

PMID- 15975732
TI  - Correspondence between Interactive Voice Response (IVR) and Timeline Followback
      (TLFB) reports of drinking behavior.
AB  - This study compared reports of alcohol consumption using an Interactive Voice
      Response (IVR) system and the Timeline Followback (TLFB). One hundred eighty-two
      daily smokers who were not alcohol dependent provided once daily reports of
      alcohol consumption using an IVR system and participated in a weekly TLFB
      interview. The reporting time period was 7 days after participants attempted to
      quit smoking as part of participation in a smoking cessation clinical trial. The
      results revealed moderate to high correlations between reports of drinking
      behavior as assessed by IVR and TLFB. Reporting biases for both IVR and TLFB were
      approximately equal, with a slight trend toward underreporting drinking on the
      TLFB. Compliance with the IVR system was poor. This study provides preliminary
      evidence that it is possible to use an IVR system for the assessment of alcohol
      use in smokers participating in a clinical trial, and IVR seems to adequately
      assess drinking behavior in those that use the system. However, future studies
      should focus on improving compliance with IVR in this population.

PMID- 15975733
TI  - Does the cell-brain theory work in explaining carcinogenesis?
AB  - As a major microtubule-organizing center, the centrosome, together with the
      embedded centrioles and connecting filaments (or microtubules), has lately been
      proposed to be the "brain" of a cell. Although there are a lot of works to be
      done to test this hypothesis, emerging data have suggested that this centrosome
      centered "cell brain" is playing increasingly important roles in cell control.
      Genes seem not to tell the whole story, despite the commonly held view that
      genetic alteration is the cause of most medical problems including cancer
      development. Although the mechanisms through which gene expression and protein
      synthesis are regulated remain to be studied, current advances in our
      understanding of the roles of the centrosome in the regulation of DNA synthesis,
      DNA repair, cell cycle, apoptosis and in the maintenance of genetic stability are
      challenging our tradition thoughts. Genetic alterations may be repaired by the
      centrosome-centered "cell brain"-mediated self-defense, but the cell brain
      defects intend to cause genetic alterations, which, in turn, may result in cancer
      development. Further understanding of the roles of the centrosome/cell brain in
      these and other new aspects are becoming very helpful in comprehending why and
      how medical problems including tumors develop. Meanwhile, it suggests that great
      attention should be given to the centrosome/cell brain, instead of gene alone
      when treating medical problems, which is discussed in this paper on the basis of
      cell brain theory and may prove helpful in shedding light on the often
      paradoxical observations seen in cell control, particularly in cancer
      development.

PMID- 15975734
TI  - Bioactivity guided isolation of antimicrobial compounds from Lythrum salicaria.
AB  - Lythrum salicaria extracts showed activity against the phytopathogenic fungus
      Cladosporium cucumerinum and activity against the bacteria Staphylococcus aureus,
      Proteus mirabilis and Microccocus luteus. Bioautography on thin-layer
      chromatograms was used to isolate the two antifungal triterpenoids oleanolic and
      ursolic acid. The hexahydroxydiphenoyl ester vescalagin was isolated as active
      principle of the antibacterial activity. Furthermore, the flavon-C-glucosides
      vitexin, isovitexin, orientin and isoorientin were isolated.

PMID- 15975735
TI  - In vitro antiprotozoal activity of the leaves of Artemisia ludoviciana.
AB  - The inhabitants of Northeast of Mexico use an infusion of leaves from Artemisia
      ludoviciana as an antidiarrheal remedy. The aqueous, methanol, acetone and hexane
      leaf extracts from mature plants were found to be active in vitro against the
      parasitic protozoa Entamoeba histolytica and Giardia lamblia.

PMID- 15975736
TI  - Discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) in
      humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine
      and placebo.
AB  - In animals, two-choice drug discrimination studies have demonstrated that the
      behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) are mediated by
      dopaminergic and serotonergic systems. In order to delineate the relative role of
      these systems, three-choice paradigms have been used in animals, with findings
      indicating a more prominent role for serotonin. Human studies assessing the
      subjective and physiological effects of MDMA have also indicated a mixed action.
      To parallel animal studies, the participants in the present study were trained to
      discriminate among a prototypic dopaminergic agonist, d-amphetamine, a prototypic
      serotonergic agonist, meta-chlorophenylpiperazine (mCPP) and placebo and then
      were tested with two doses of MDMA. In addition, subjective and physiological
      effects were measured. The results demonstrated that humans could be trained to
      discriminate among 20 mg d-amphetamine, 0.75 mg/kg mCPP and placebo. When tested
      with 1.0 and 1.5 mg/kg, half the participants reported MDMA to be like
      amphetamine and half like mCPP. There were no clear differences between these two
      groups in other dimensions, although there was an indication that the individuals
      who discriminated MDMA as d-amphetamine were more sensitive to the effects of all
      the drugs. The subjective effects of all three drugs overlapped, although the
      effects of MDMA appeared more amphetamine-like.

PMID- 15975737
TI  - Evolution of nuclearly encoded mitochondrial genes in Metazoa.
AB  - All Metazoan nuclear genomes underwent a continuous process of both complete and
      partial genetic material gain and loss. The forces modulating these events are
      also subject to the strict interaction between nuclear and mitochondrial (mt)
      genome. In this context we investigate the evolution of nuclear genes encoding
      proteins which target the mitochondrion, with a particular attention to genes
      involved in oxidative phosphorylation (OXPHOS), one of the most ancient and
      conserved functions. To examine thoroughly the evolutionary strategies that
      preserve OXPHOS and coordinate the two cellular genomes, a comparative analysis
      has been carried out for 78 OXPHOS gene families in several Metazoa (insects,
      tunicates, fishes and mammals). We demonstrate that the duplication rate of
      OXPHOS genes increases passing from invertebrates to vertebrates consistently
      with the total increase in genome size, but all species are prone to negatively
      select OXPHOS duplicates compared to the general trend of nuclear gene families.
      These results are consistent with the 'balance hypothesis' and, at least in
      insects, the expression of duplicate genes is low and strongly testis-biased.

PMID- 15975738
TI  - Thymidine phosphorylase mutations cause instability of mitochondrial DNA.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive disorder characterized by ptosis and progressive external
      ophthalmoplegia, peripheral neuropathy, severe gastrointestinal dysmotility,
      cachexia and leukoencephalopathy. Muscle biopsies of MNGIE patients have revealed
      morphologically abnormal mitochondria and defects of respiratory chain enzymes.
      In addition, patients harbor depletion, multiple deletions, and point mutations
      of mitochondrial DNA (mtDNA). This disorder is caused by loss-of-function
      mutations in the gene encoding thymidine phosphorylase (TP) a cytosolic enzyme.
      In MNGIE patients, TP activity is very low or absent resulting in dramatically
      elevated levels of plasma thymidine and deoxyuridine. We have hypothesized that
      the increased levels of thymidine and deoxyuridine cause mitochondrial nucleotide
      pool imbalances that, in turn, generate mtDNA alterations.

PMID- 15975740
TI  - Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis
      of porcine proliferative enteropathy.
AB  - A specific enzyme-linked immunosorbent assay (ELISA) for detection of antibodies
      to the porcine pathogen Lawsonia intracellularis was developed and evaluated
      using sera from naive, naturally infected as well as experimentally infected
      pigs. On the basis of 37 serum samples collected from experimentally infected
      pigs and 62 serum samples from naturally infected pigs the sensitivity of the
      ELISA was calculated to 98.0%. The specificity of the test was 99.3%, calculated
      on the basis of 273 serum samples collected in six herds free of L.
      intracellularis after medicated eradication. The novel ELISA was a specific and
      sensitive method for detecting specific antibodies, and may be a good alternative
      to the existing serological tests for L. intracellularis. It may be usable for
      diagnosis of proliferative enteropathy and for determination of a herd's
      epidemiologic status.

PMID- 15975741
TI  - Biochemical characterisation of some non fermenting, non arginine hydrolysing
      mycoplasmas of ruminants.
AB  - The pattern and kinetics of substrate oxidation by type and recent field strains
      of Mycoplasma agalactiae, Mycoplasma bovis, Mycoplasma bovigenitalium and
      Mycoplasma ovine/caprine serogroup 11 were investigated by measurement of oxygen
      uptake. Metabolism of a range of organic acids, sugars and alcohols was detected.
      All the test strains were unable to oxidise sugars, glycerol and the organic
      acids, fumarate, malate and alpha-ketoglutarate (1 mM). All strains oxidised
      organic acid l-lactate, 2-oxobutyrate and pyruvate and demonstrated the ability
      to oxidise alcohols, particularly isopropanol, which was oxidised at a high rate
      and high affinity (0.5 mol/mol isopropanol). Its oxidation was consistent with
      acetone formation, which may be of important in relation to pathogenicity. All
      strains oxidised similar substrates, however differences were observed between
      strains in terms of the relative rates and kinetic values for some substrates.

PMID- 15975742
TI  - Developmental changes in serum half-life of (EZ)-cyclobilirubin.
AB  - BACKGROUND: Phototherapy has been a standard treatment for neonatal
      hyperbilirubinemia for more than 40 years, but it has remained sub-optimal. AIMS:
      To clarify the developmental changes in parameters of (4E, 15Z)-cyclobilirubin
      ((EZ)-C) elimination in order to obtain basic data for establishing optimal
      phototherapy. STUDY DESIGN: Blood samples were taken at regular intervals after
      stopping phototherapy, and bilirubin fractions were analyzed by high-performance
      liquid chromatography. SUBJECTS AND METHODS: The subjects were 46 infants with
      hyperbilirubinemia who underwent phototherapy. The gestational age and birth
      weight of the subjects ranged from 25.0 to 41.0 weeks and from 656 to 3810 g,
      respectively, and the age at cessation of phototherapy was a median of 5 days. A
      kinetic model of (EZ)-C elimination was established, and the serum half-life of
      (EZ)-C was calculated on the basis of the determined model. Relationships of the
      half-life of (EZ)-C with birth weight and gestational age were investigated.
      RESULTS: Serum (EZ)-C elimination followed a first-order kinetic model in 43
      infants and a zero-order kinetic model in three extremely low birth weight
      infants. The half-life of (EZ)-C calculated on the basis of a first-order
      elimination model in serum ranged from 68 to 274 min and showed weak negative
      correlations with birth weight and gestational age. CONCLUSIONS: Serum (EZ)-C
      excretion followed a first-order kinetic model in most of the neonates. The half
      life of (EZ)-C becomes more prolonged in the very low birth weight infant and
      early gestational age.

PMID- 15975743
TI  - The effectiveness of training in Prechtl's method on the qualitative assessment
      of general movements.
AB  - BACKGROUND: Prechtl's method on the qualitative assessment of general movements
      (GMs) is a highly sensitive and specific diagnostic tool for the assessment of
      the integrity of the young nervous system. AIM: To find out whether the ability
      to assess GMs correctly could be gained after receiving a few days' standardised
      training. STUDY DESIGN: We evaluated 700 scoring sheets (containing a total of
      8019 assessments) from the final tests of 18 training courses held between 1997
      and 2002. RESULTS: Eighty-three per cent of the assessments were correct after
      completing a 4- to 5-day training course. The correct discrimination between
      normal and abnormal GMs was 92%. It proved more difficult to assess infants
      correctly if they had been recorded around term age. CONCLUSION: Standardised
      training courses enable professionals in the field of infant and child neurology
      to apply Prechtl's method of GM assessment accurately.

PMID- 15975744
TI  - Effect of different thawing temperatures on the viability, in vitro fertilizing
      capacity and chromatin condensation of frozen boar semen packaged in 5 ml straws.
AB  - The effect of two different thawing temperatures on frozen boar semen viability,
      in vitro fertilizing capacity and chromatin condensation and stability was
      studied. Freeze-thaw motility, normal apical ridge (NAR), in vitro fertilizing
      (IVF) capacity and chromatin condensation and stability were evaluated after
      thawing at 42 degrees C, 40s and 50 degrees C, 40s. Chromatin condensation degree
      was determined by flow cytometry, using propidium iodide as fluorochrome
      intercalating agent, and chromatin stability was evaluated by the same procedure
      after inducing sperm chromatin decondensation with ethylene diamine tetraacetic
      acid (EDTA) and sodium dodecyl sulfate (SDS). The results showed that thawing
      straws at 42 degrees C, 40s significantly reduced motility compared to straws
      thawed at 50 degrees C, 40s. NAR, penetration, monospermy and polyspermy were not
      different between the two groups of samples thawed at different temperatures.
      Chromatin was significantly more compact when thawing was performed at 50 degrees
      C, but its stability did not show any difference relative to thawing at 42
      degrees C. It is suggested that the interactions involved in chromatin
      overcondensation had a non-covalent nature.

PMID- 15975745
TI  - Veterinary clinical application of GnRH--questions of efficacy.
AB  - The efficacy of GnRH treatments are reviewed in relation to prevention of embryo
      mortality, control of follicle development in synchronization programmes using PG
      as luteolysin, induction of ovulation in post-partum anoestrus and in bovine
      cystic ovarian disease. It is suggested that in cattle that GnRH is effective in
      increasing pregnancy rates when given either at the time of insemination (first
      or repeat) or between days 11 and 14 after insemination. Evidence is also
      presented for positive effects on pregnancy rates in sheep, mares and sows. Use
      of GnRH as an integral part of synchronising regimens where it is given 7 days
      before PG and then again 48-60 h after PG appears to be effective in increasing
      the synchrony of ovulation in controlled breeding programmes. The main
      synchronizing effect seems to reside in the second GnRH injection whereas the
      importance of the first is in prolonging the luteal phase in those cows treated
      late in the cycle. The published work on the potential use of GnRH to induce
      ovulation in anovulatory cattle is reviewed. Neither bolus dose injections,
      pulsatile, continuous infusion, nor controlled release formulations of GnRH, have
      yet proved effective in inducing fertile ovulations in a predictable or
      consistent manner. It is suggested that this is due to the variability of
      follicular status when treatment is initiated. GnRH is commonly used in the
      treatment of bovine cystic ovarian disease. However, although stimulating
      ovulation/luteinisation of a new follicle and luteinisation of the cyst,
      fertility of treated cattle remains very poor and it is suggested that a better
      understanding of the disease is needed before more effective treatments can be
      developed.

PMID- 15975746
TI  - A comparison of chemical reference materials for solution calorimeters.
AB  - Solution calorimeters are based on semi-adiabatic or isothermal heat-conduction
      principles and differ in the way they record data. They also have different
      measuring sensitivities and require different quantities of solute and solvent.
      As such, the choice of chemical test substance is not straightforward. Usually
      the dilution of KCl is recommended; it is possible to purchase a reference sample
      of KCl that has a certified enthalpy of solution and this standard material is
      usually used to test semi-adiabatic instruments. Here, we review the suitability
      of a range of chemical test substances (KCl, sucrose and Tris) for an isothermal
      heat-conduction solution calorimeter. It was found that KCl was not the best test
      material because its relatively high enthalpy of solution (DeltasolH)
      necessitated the use of small samples (2 mg), resulting in a relatively large
      standard deviation (sigman-1) in the values recorded (DeltasolH=17.14+/-0.49 kJ
      mol-1); furthermore, KCl data must be corrected to account for the effect of
      dilution, although the correction was found to be small (0.07 kJ mol-1) under the
      experimental conditions employed here. Sucrose appears to be a much more robust
      test material for isothermal heat-conduction instruments because its lower
      enthalpy of solution allows the use of much larger samples (20 mg), which
      minimises experimental errors. The DeltasolH value returned (6.14+/-0.08 kJ mol
      1) is in excellent agreement with the literature. It is also cheap, readily
      available and requires minimal preparation although its widespread use would
      require the preparation of a certified reference sample.

PMID- 15975739
TI  - Expressed sequence tags from the laboratory-grown miniature tomato (Lycopersicon
      esculentum) cultivar Micro-Tom and mining for single nucleotide polymorphisms and
      insertions/deletions in tomato cultivars.
AB  - Laboratory-grown miniature tomato (Lycopersicon esculentum) cultivar Micro-Tom
      has attracted attention as a host for functional genomics research. In this
      study, we generated 35,824 expressed sequence tags (ESTs) from leaves and fruits
      of Micro-Tom. The ESTs comprised 10,287 unigenes (5007 contigs and 5280
      singletons), including 1858 novel tomato unigenes. Of the 18 unigenes that shared
      strong homology with tobacco chloroplast genome sequences, one unigene was likely
      derived from polyadenylated transcripts of the atpH gene. Interestingly, ESTs for
      vacuolar invertase, pectate lyase and alcohol acyl transferase were
      underrepresented in the Micro-Tom data set. From all of the ESTs, we mined 2039
      candidate single nucleotide polymorphisms (SNPs) and 121 candidate insertions and
      deletions (indels) based on homology with four tomato inbred lines, E6203, R11
      13, Rio Grande PtoR and R11-12, and a wild relative, L. pennellii TA56, for which
      sequence data was publicly available with more than 5000 entries. Direct genome
      sequencing of several SNP or indel sites in Micro-Tom and L. esculentum E6203
      suggested that more than 69% of the candidate sites were truly polymorphic,
      making them useful for the preparation of DNA markers.

PMID- 15975748
TI  - Predicting the residential location of a serial commercial robber.
AB  - Residential location of a serial offender can potentially be predicted by using
      models created from home to crime site journeys of solved crimes in the area [N.
      Levine, Journey-to-crime estimation, retrieved 23 October 2003 from
      http://www.icpsr.umich.edu/NACJD/crimestat/CrimeStatChapter.9.pdf, last visited 1
      February 2005]. Aims of this study were: (1) to examine the accuracy of this
      technique, (2) to explore relation of modus operandi (m.o.) to the distance the
      crime was committed from home and (3) to analyse whether the accuracy of
      prediction is enhanced by taking the m.o. into account. Data consisted of 76
      commercial robbery series from the Greater Helsinki area. Accuracy of prediction
      was tested by using leave-one-out technique: the series which the predicting
      function was applied to was never part of the function used to predict. The
      functions allowed limiting the area to be searched to 4.7% (Mdn, IQR = 31.0%) of
      the study area generally, and to 1.0% (Mdn, IQR = 2.6%) when the suspect's
      spatial behaviour conformed to the circle hypotheses presented by Canter and
      Larkin [D. Canter, P. Larkin, The environmental range of serial rapists, J.
      Environ. Psychol. 13 (1993) 63-69]. Significant correlations between m.o. and the
      length of the journey-to-crime were found, but this information did not enhance
      accuracy of prediction. Low percentage of marauder style perpetrators in the data
      gives support to the possible separation of hypotheses of underlying spatial
      behaviour in instrumental crimes versus crimes of interpersonal violence or
      arson. Suggestions for development of investigative tools are presented.

PMID- 15975749
TI  - Driving under the influence of chlormethiazole.
AB  - This article describes a case of driving under the influence of the sedative
      hypnotic-anticonvulsant drug chlormethiazole. The suspect, who was a physician,
      was driving dangerously on a busy highway and caused a traffic collision. When
      apprehended by the police, the man had bloodshot and glazed eyes and pupil size
      was enlarged. He could not answer the questions properly and his gait was
      unsteady. A roadside breath-alcohol screening test was positive but an evidential
      breath-alcohol test conducted about one hour later was below the legal limit for
      driving of 0.10 mg/L (10 microg/100 mL or 0.021 g/210 L). Because of the special
      circumstances of the traffic crash and the man's appearance and behaviour, the
      police suspected that drugs other than alcohol were involved and obtained a
      venous blood sample for toxicological analysis. The blood contained 0.23 mg/g
      alcohol, which is above the legal limit for driving in Sweden 0.20 mg/g (20
      mg/100 mL or 0.020 g/100 mL), and codeine was also present at a therapeutic
      concentration of 0.02 mg/L. The conflict between the clinical signs of impairment
      and the toxicology report prompted a reanalysis of the blood sample with major
      focus on sedative-hypnotic drugs. Analysis by capillary GC-NPD identified
      chlormethiazole at a concentration of 5mg/L, the highest so far encountered in
      traffic cases in Sweden. In 13 other impaired driving cases over 10 years the
      mean (median) and range of concentrations of chlormethiazole were 1.6 mg/L (1.6
      mg/L) and 0.3-3.3 mg/L. This case report underscores the need to consider
      clinical observations and the person's behaviour in relation to the toxicology
      report when interpreting and testifying in drug-impaired driving cases.

PMID- 15975750
TI  - [A fatal case of Mediterranean spotted fever].

PMID- 15975751
TI  - [Inclusion of a rapid test in the current Health Ministry Guidelines with the
      purpose of improving anti-tetanus prophylaxis prescribed to wounded patients
      presenting at French Emergency Departments].

PMID- 15975752
TI  - [Epidemiological, clinical, etiological features of neuromeningeal diseases at
      the Fann Hospital Infectious Diseases Clinic, Dakar (Senegal)].
AB  - OBJECTIVES: This retrospective study was carried out to determine the prevalence
      of cerebromeningeal diseases at the Fann Teaching Hospital Infectious Diseases
      Clinic, in Dakar, and to describe their epidemiological, clinical, and
      etiological features. PATIENTS AND METHODS: Data was collected for analysis from
      patients files recorded from January 1, 2001 to December 31, 2003. RESULTS: Four
      hundred seventy cases were identified (11.4% of total admissions) with a M/F sex
      ratio of 1.38 and a mean age of 33 years. Eighty-nine patients were infected by
      HIV and clinical presentations included fever (78%), meningeal syndrome (57.4%),
      coma (64.9%), convulsions (19%), focal neurological deficits (15.5%), and cranial
      nerves dysfunction (7.2%). Etiologies presented as cerebral malaria (85 cases),
      purulent meningitis (51 cases), neuromeningeal cryptococcosis (37 cases),
      tuberculous meningitis (11 cases), intracranial abscess (10 cases), toxoplasma
      encephalitis (4 cases), cerebrovascular attack (11 cases), and cerebromeningeal
      hemorrhages (3 cases). In as many as 248 cases (52.8%) no etiology could be
      found. The case fatality rate was 44.5% overall (209 deaths) and 68.5% among HIV
      infected patients. Neurological sequels were found in 22 survivors (8.8%),
      consisting in focal neurological deficit (12 cases), deafness (5 cases), diplopia
      (2 cases), dementia (2 cases), postmeningitic encephalitis (1 case). CONCLUSION:
      These results show the need to improve our technical capacities in our diagnostic
      laboratories, the prevention of opportunistic infections in the course of
      HIV/AIDS infection, and the involvement of various specialists in the management
      of cerebromeningeal diseases.

PMID- 15975753
TI  - Aging, traumatic injury, and estrogen treatment.
AB  - Aged subjects are more likely than young to have a poor prognosis after traumatic
      injury. Regardless of the type of injury, from scald wound to bone fracture, aged
      have slower recoveries and suffer more complications than their younger
      counterparts. This age-dependent phenomenon may be influenced by the hyper
      inflammatory state observed in the aged referred to as 'inflamm-aging.' Having
      elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and
      tumor necrosis factor alpha (TNFalpha), in the circulation prior to injury may
      predispose the aged population to produce even higher concentrations of these
      factors after injury. Marked overproduction of pro-inflammatory cytokines leads
      to immunosuppression. Since many trauma victims do not die of their primary
      injuries, but rather succumb following infections and/or other complications at
      later time points, the functional status of the immune system is of paramount
      importance. Evidence suggests that at physiological levels, estrogen is
      beneficial to the immune system. This is due, in part, to the hormone's ability
      to boost immunity and to attenuate aberrant production of pro-inflammatory
      cytokines, thus serving as a systemic anti-inflammatory agent. In this short
      review, an examination of the effects of estrogen on inflammatory and immune
      responses that are critical to survival and recovery following traumatic injury
      will be discussed.

PMID- 15975754
TI  - A method of clustering observers with different visual characteristics.
AB  - Evaluation of observer's image perception in medical images is important, and yet
      has not been performed because it is difficult to quantify visual
      characteristics. In the present study, we investigated the observer's image
      perception by clustering a group of 20 observers. Images of a contrast-detail (C
      D) phantom, which had cylinders of 10 rows and 10 columns with different
      diameters and lengths, were acquired with an X-ray screen-film system with fixed
      exposure conditions. A group of 10 films were prepared for visual evaluations.
      Sixteen radiological technicians, three radiologists and one medical physicist
      participated in the observation test. All observers read the phantom radiographs
      on a transillumination image viewer with room lights off. The detectability was
      defined as the shortest length of the cylinders of which border the observers
      could recognize from the background, and was recorded using the number of
      columns. The detectability was calculated as the average of 10 readings for each
      observer, and plotted for different phantom diameter. The unweighted pair-group
      method using arithmetic averages (UPGMA) was adopted for clustering. The
      observers were clustered into two groups: one group selected objects with a
      demarcation from the vicinity, and the other group searched for the objects with
      their eyes constrained. This study showed a usefulness of the cluster method to
      select personnels with the similar perceptual predisposition when a C-D phantom
      was used in image quality control.

PMID- 15975755
TI  - Development and validation of a dissolution test for a once-a-day combination
      tablet of immediate-release cetirizine dihydrochloride and extended-release
      pseudoephedrine hydrochloride.
AB  - A dissolution test for a once daily combination tablet containing 10 mg of
      cetirizine dihydrochloride (cetirizine HCl) for immediate release and 240 mg of
      pseudoephedrine hydrochloride (pseudoephedrine HCl) for extended release was
      developed and validated according to current ICH and FDA guidelines. The
      cetirizine HCl is contained within an outer layer of the tablet while a
      semipermeable membrane of cellulose acetate and polyethylene glycol controls the
      rate at which pseudoephedrine HCl is released from the tablet core. The
      dissolution method, which uses USP apparatus 2 with paddles rotating at 50 rpm,
      1000 ml of deaerated water as the dissolution medium, and reversed-phased HPLC
      for quantitation, was demonstrated to be robust, discriminating, and
      transferable. These test conditions were selected after it was demonstrated that
      the cetirizine HCl portion of the tablet rapidly dissolved in aqueous media over
      the physiologically relevant pH range of 1.1-7.5, and that the extended-release
      profile of pseudoephedrine HCl was independent of dissolution conditions (i.e.,
      apparatus, pH, and agitation).

PMID- 15975756
TI  - Qualitative evaluation of Chronic Disease Self Management Program (CDSMP) in
      Shanghai.
AB  - OBJECTIVES: To explore the impact of Chronic Disease Self-Management Program
      (CDSMP) on participants' perception of their behavior, health status and quality
      of life and how the program achieve its benefits, and to collect suggestions for
      future improvement and dissemination. METHODS: Qualitative data were obtained
      from 57 participants attending all sessions of the CDSMP course using semi
      structured interviews and analyzed using content analysis. RESULTS: The
      interviewees perceived that CDSMP improved their knowledge, self-management
      skills, positive health behavior, increased self-confidence, health status and
      quality of life. Behavior change and self-efficacy were the two main transmitters
      of the effectiveness of CDSMP in Shanghai. The identified deficiencies focused on
      language, size and style of helpbook and the lack of Chinese relaxing exercises.
      CONCLUSION: CDSMP was perceived to be effective to participants mainly through
      behavior change and self-efficacy development, though it had a few deficiencies
      to be modified. PRACTICE IMPLICATIONS: CDSMP in Shanghai needs further work and
      research on the content and delivery modification for future improvement and
      dissemination.

PMID- 15975757
TI  - Attitudes of physicians, nurses and relatives towards end-of-life decisions
      concerning nursing home patients with dementia.
AB  - OBJECTIVE: For many nursing home patients in the advanced stages of dementia, a
      decision to start or forgo treatment has to be taken at the end of their life. It
      is very important for the peace of mind of all involved in such decision-making
      that there is agreement on which decision is in the best interest of the patient.
      It is thus important to investigate the attitude of physicians, nurses and
      relatives towards medical end-of-life decisions concerning patients with
      dementia, so that the policy in nursing homes can be tuned to stimulate dialogue
      and understanding between all parties. METHODS: Fifteen statements about
      artificial nutrition and hydration (ANH), advance directives, hastening death,
      self-determination and euthanasia, and nursing home policy were presented to
      physicians, nurses and relatives of nursing home patients suffering from
      dementia. RESULTS: In general, physicians, nurses and relatives agree on many
      aspects of end-of-life decision-making for nursing home patients with dementia.
      However, on some issues the outcomes of the decision-making may differ. Relatives
      attach more importance to advance directives than physicians, and have more
      permissive attitudes towards hastening death. CONCLUSION: Although physicians,
      nurses and relatives are all guided by the best interest of the patient, it seems
      that differences in religious beliefs, perspective of the patient, and
      responsibility can lead to different attitudes towards end-of-life decisions.
      PRACTICE IMPLICATIONS: Physicians should discuss end-of-life decisions more
      openly. Physicians should be aware of the influences on attitudes and incorporate
      them into communication about end-of-life decisions.

PMID- 15975758
TI  - Training simulator for sentinel node biopsy (SLNB).

PMID- 15975759
TI  - Randomized trial of cytoreduction followed by intraperitoneal chemotherapy versus
      cytoreduction alone in patients with peritoneal sarcomatosis.
AB  - PURPOSE: In order to decrease loco-regional relapse after complete resection of
      peritoneal sarcomatosis (PS), the role of intraperitoneal chemotherapy (IPEC) was
      prospectively evaluated. METHODS: Patients (pts) with completely resected PS were
      randomized between adjunction of IPEC or not. IPEC consisted of doxorubicin,
      0.1mg/kg and cisplatin, 15 mg/m(2) per day for 5 consecutive days. Primary
      endpoint was survival, measured as time from randomization to death. The
      scheduled number of patients needed was 40 in order to detect a minimal increase
      of 40% overall survival with the adjunction of IPEC with a power of 80%. RESULTS:
      Thirty-eight consecutive pts have been randomized, 19 in each group. Ratio of
      retroperitoneal (RPS) and visceral (VS) sarcomatosis were 9/10 and 6/13 in IPEC-
      and IPEC+ group, respectively. Histoprognostic grade, Sugarbaker's score and mean
      number of resected organs were similar in both groups. There were no toxic deaths
      and morbidity was similar in both groups (four pts in each group). The median
      follow-up is 60 months. The median local relapse-free, metastatic relapse-free
      survival and overall survival were identical in both groups (12.5, 18 and 29
      months, respectively), with no difference between RPS and VS sarcomatosis.
      CONCLUSION: Administration of IPEC after a macroscopically complete surgery did
      not allow to increase greatly the outcome of pts. Complete surgery remains the
      cornerstone of the treatment of patients with sarcomatosis with best results for
      low grade sarcomatosis.

PMID- 15975760
TI  - Comparison between the fifth and sixth editions of the AJCC/UICC TNM staging
      systems for hepatocellular carcinoma: multicentric study on 393 cirrhotic
      resected patients.
AB  - AIMS: To compare the prognostic efficacy of the 5th and 6th edition of the TNM
      staging system for HCC. METHODS: We retrospectively applied the old and the new
      systems to 393 resected patients, comparing the efficacy of both in prognostic
      evaluation. RESULTS: The 1-, 3- and 5-year overall survival rates were 89.7, 71.1
      and 56.3%, respectively. The 1-, 3- and 5-year disease-free survival rates were
      79.4, 54.6 and 39.4%, respectively. Among the factors evaluated, Child's grade B
      and C (p=0.001) and presence of multiple nodules (p=0.01) were found to be
      related either to a worse long-term survival or to a worse disease-free survival.
      Stratifying patient survivals according to the old TNM system, we found
      significant differences only between stages II and IIIA (p=0.001); otherwise
      stages I and II (p=0.9) as well as stages IIIA and IVA (p=0.9) showed similar
      survival rates. Analysing the new TNM system, we found a more homogeneous staging
      stratification, with significant differences both between stage I and II (p=0.02)
      and between stage II and IIIA (p=0.05). CONCLUSIONS: In the present multicentric
      study, long term overall and disease-free survival after liver resection for HCC
      was strongly affected by the number of tumours and the underlying liver disease.
      Our results suggest that the new classification appears to achieve an accurate
      stratification of patients, simpler than the previous edition, as well as a more
      reliable comparative analysis of outcome after hepatic resection for HCC.

PMID- 15975762
TI  - Correlation between dopaminergic neurons, acetylcholinesterase and nicotinic
      acetylcholine receptors containing the alpha3- or alpha5-subunit in the rat
      substantia nigra.
AB  - The aim of this study was to investigate the relationship between the cells
      possessing the alpha3 or alpha5 nicotinic acetylcholine receptor subunits and the
      enzyme acetylcholinesterase, with respect to tyrosine hydroxylase immunoreactive
      dopaminergic neurons in the rat substantia nigra. Most, but certainly not all,
      acetylcholinesterase immunoreactive cells were located in the pars compacta. In
      the substantia nigra pars compacta there were in turn two populations of
      acetylcholinesterase containing neurons: those that were tyrosine hydroxylase
      reactive and those that were not. Double label studies, that included an antibody
      immunoreactive against a common immunogen on alpha1 of muscle and alpha3 and
      alpha5 neuronal nicotinic acetylcholine receptor subunits, revealed that nearly
      all nicotinic receptor positive cells were also tyrosine hydroxylase neurons.
      However, a minority non-tyrosine hydroxylase population was alpha3- and/or alpha5
      nAChR positive and these were always AChE-immunoreactive. In summary, there
      appears to be a close correlation between nicotinic receptors and
      acetylcholinesterase in the substantia nigra, irrespective of the transmitter
      phenotype in different neuronal subpopulations.

PMID- 15975761
TI  - Human embryonic stem cells as a model for nutritional programming: an evaluation.
AB  - Our laboratory is evaluating whether an epigenetic mechanism involving
      alterations in DNA methylation can alter the trajectory of embryonic/fetal
      development in response to maternal nutrients. A similar mechanism may operate in
      embryo culture environments commonly used in human assisted conception. Since
      developmental studies on early human embryos in utero are obviously not possible,
      we have begun to investigate the utility of human embryonic stem cells (hESC) to
      uncover potential programming mechanisms. This review highlights some of the
      advantages and problems associated with such a model and suggests that these
      issues are also broadly applicable to utility of hESC for more general toxicology
      and drug screening applications.

PMID- 15975763
TI  - Brief report: parental descriptions of sleep problems in children with autism,
      Down syndrome, and Prader-Willi syndrome.
AB  - Children with an intellectual disability (ID) are at high risk of developing
      sleep problems. The extent to which the prevalence and nature of sleep problems
      in these children is dependent on the disorder underlying their intellectual
      impairments remains unclear. This study examined and compared parental
      descriptions of sleep problems in children with autism (n = 37), Down syndrome
      (DS; n = 15), Prader-Willi syndrome (PWS; n = 29), presumed familial intellectual
      disability (FID; n = 29), and typically developing children (TD; n = 55) in order
      to determine any influences of disorder on sleep patterns. The prevalence of
      sleep problems in the disability groups was at least four times higher than for
      TD children. Sleep problems were more prevalent in autism than the other
      disorders. Settling difficulties and co-sleeping were more common in the children
      with autism, whereas sleep maintenance problems were common in autism, DS, and
      FID, and daytime napping and excessive daytime sleepiness differentiated the
      children with PWS. These findings are discussed in light of the specific
      disorders, and with respect to the impact that sleep problems can have on the
      child and his/her family.

PMID- 15975765
TI  - Assessment of pain in temporomandibular disorders: the bio-psychosocial
      complexity.
AB  - Temporomandibular joint disorders (TMD) affect the joint, the masticatory
      muscles, or are expressed as a clinical combination of these two factors. The
      aims of this study were to: (i) identify the clinical and psychosocial factors
      that aid in the diagnosis and classification of acute and chronic TMD, (ii)
      determine specific initiating and perpetuating factors which may act as a guide
      to differentiate between acute and chronic TMD, (iii) identify factors which
      might predispose to conversion from acute to chronic TMD. Twenty-two patients
      were examined in the pain clinics at the Eastman Dental Institute. The assessment
      technique incorporated questionnaires, clinical history and examination including
      dental panoramic tomography. The results of this pilot study show a significant
      correlation between mood and enjoyment of life in both groups, mood and
      relationships in the chronic group, average pain and sleep in the chronic group,
      average pain and eating-chewing in the chronic group, and phobia for physical
      disease with trust in clinicians in the chronic group. The bio-psychosocial model
      of pain is an important appraisal tool. The newly designed TMD Pain Assessment is
      described with good results.

PMID- 15975764
TI  - Nicotine effects on the activity of mice exposed prenatally to the nicotinic
      agonist anatoxin-a.
AB  - Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria,
      and has caused numerous deaths of wildlife, livestock and domestic animals world
      wide. Several studies in the literature have shown that exposure of mice and rats
      to nicotine early in development alters its effects when the rodents are
      subsequently challenged with nicotine. We therefore determined the effect of
      nicotine on the motor activity of adult mice that had been exposed prenatally to
      anatoxin-a. Pregnant CD-1 mice received either saline vehicle or one of two doses
      of (+/-) anatoxin-a (125, 200 microg/kg), i.p., on GD13-17. As adults (8 months),
      control mice of both genders were used to determine the effect of nicotine (0,
      0.1, 0.3, 1.0 or 3.0 mg/kg, s.c.) on motor activity measured for 30-min in a
      photocell device. Under these conditions, nicotine produced dose-related
      decreases in both horizontal and vertical activity, with an ED50 estimated to be
      0.65 mg/kg. Next, additional control mice and mice exposed prenatally to anatoxin
      a received the nicotine ED50 and saline vehicle, in a counterbalanced fashion,
      with one week separating treatments. Nicotine decreased both horizontal and
      vertical activity in all mice, regardless of prenatal anatoxin-a treatment. Thus,
      no enduring effects of prenatal anatoxin-a were obtained in adult mice following
      nicotine challenge.

PMID- 15975766
TI  - The synergistic anticonvulsant effect of agmatine and morphine: possible role of
      alpha 2-adrenoceptors.
AB  - Recent demonstrations of the anticonvulsant properties of agmatine suggest it may
      be considered as a potential adjunct for protection against seizure. We
      investigated the possibility of an additive anticonvulsant effect between low
      doses of agmatine and morphine. The thresholds for the clonic seizures induced by
      the intravenous administration of gamma-aminobutyric acid (GABA)-antagonist,
      pentylenetetrazole (PTZ) were assessed in mice. Morphine at lower doses (1
      3mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure
      threshold. Pretreatment with a per se non-effective dose of agmatine (1mg/kg)
      potentiated the anticonvulsant effect of morphine. The combination of
      subeffective doses of agmatine and morphine led to potent anticonvulsant effects.
      The pro-convulsant effect of morphine was attenuated by agmatine. Yohimbine with
      a dose (1mg/kg) incapable of affecting seizure threshold reversed the effect of
      agmatine on both anticonvulsant and pro-convulsant effects of morphine. These
      results suggest that agmatine potentiates the anticonvulsant effect of morphine
      and alpha 2-adrenoceptors may be involved in this effect.

PMID- 15975767
TI  - Association of education and cognitive status in Brazilian elderly
      institutionalized patients with schizophrenia.

PMID- 15975768
TI  - Visual processing in schizophrenia: Structural equation modeling of visual
      masking performance.
AB  - Schizophrenic patients consistently demonstrate performance deficits on visual
      masking procedures. In visual masking, the subject's ability to process a target
      stimulus is reduced by another stimulus (mask) presented either before (forward
      masking) or after (backward masking) the target. Masking procedures employed in
      schizophrenia research have used several experimental paradigms. Most early
      studies have used high-energy masks (i.e., the mask is stronger than the target)
      and spatially overlapping target and mask. More recently, studies have begun to
      employ relatively weak (i.e., low-energy) masks, as well as masks that surround,
      but do not spatially overlap, the target. Data for forward and backward masking
      components of four masking conditions (target location and identification with a
      high-energy mask, target identification with a low-energy mask, and target
      identification with equal energy paracontrast/metacontrast) were collected from
      75 patients with schizophrenia. Based on theoretical distinctions among masking
      procedures, we compared four models of visual masking using structural equation
      modeling. Although high zero-order correlations were found among the masking
      parameters, a four-factor model, in which factors were separated on the type of
      response (target location and identification), the shape of the function
      (monotonic and non-monotonic), and the overlap of the stimuli (overlapping and
      non-overlapping), provided the best fit for the data. These findings suggest that
      the four masking procedures used in this study may tap unique aspects of visual
      processing and are not redundant. The results also support theories of the
      different mechanisms underlying performance on these measures.

PMID- 15975769
TI  - Nosocomial infections due to methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant enterococci at a university hospital in Taiwan from 1991 to
      2003: resistance trends, antibiotic usage and in vitro activities of newer
      antimicrobial agents.
AB  - A rapid increase of nosocomial methicillin-resistant Staphylococcus aureus (MRSA)
      infection (from 39% in 1991 to 75% in 2003) and vancomycin-resistant enterococci
      (VRE) (from 1.2% in 1996 to 6.1% in 2003) at a university hospital in Taiwan was
      found. The noticeable rise of MRSA and VRE was significantly correlated with the
      increased consumption of glycopeptides, beta-lactam-beta-lactamase inhibitor
      combinations, extended-spectrum cephalosporins, carbapenems and fluoroquinolones
      (Pearson's correlation coefficient, P < 0.05). Minimum inhibitory concentrations
      (MICs) of 100 non-duplicate blood isolates of MRSA (in 2003) and of 25 non
      duplicate isolates of vancomycin-resistant Enterococcus faecalis and 172
      vancomycin-resistant Enterococcus faecium (in 1996-2003) causing nosocomial
      infection recovered from various clinical specimens of patients treated at the
      hospital to nine antimicrobial agents were determined by the agar dilution
      method. All of these isolates were susceptible to linezolid and were inhibited by
      0.5mg/L of tigecycline, and all MRSA isolates were inhibited by daptomycin 1mg/L,
      including two isolates of MRSA with heteroresistance to vancomycin. Daptomycin
      had two-fold better activity against vancomycin-resistant E. faecalis (MIC90, 2
      mg/L) than against vancomycin-resistant E. faecium (MIC90, 4 mg/L). Decreased
      susceptibilities of vancomycin-resistant E. faecium and MRSA to
      quinupristin/dalfopristin (non-susceptibility 25% and 8%, respectively) were
      found. Telithromycin had poor activity against the isolates tested (MIC90, 8
      mg/L). Linezolid, daptomycin and tigecycline may represent therapeutic options
      for infections caused by these resistant Gram-positive organisms.

PMID- 15975770
TI  - The C2 variant of human serum transferrin retains the iron binding properties of
      the native protein.
AB  - The tryptic digests of blood samples obtained from transferrin C1 and C2 (TfC 1
      and TfC2 hereafter) genotypes were analysed by Liquid Chromatography coupled to
      Electrospray Mass Spectrometry (LC/ESI--MS/MS). The analytical results confirmed
      the single base change in exon 15 of the Tf gene. The solution behaviour and the
      iron binding properties of the two Tf variants were studied by UV-visible
      spectrophotometry and by circular dichroism. It appears that TfC2 globally
      manifests the same spectral features as the native protein. The local
      conformation of the two iron binding sites is conserved in the two Tf variants as
      evidenced by the visible absorption and CD spectra. Also, the iron binding
      capacities and their pH-dependent profiles are essentially the same. Overall, our
      investigation points out that the single amino acid substitution in TfC2 (Pro 570
      Ser) does not affect the general conformation of the protein nor the local
      structure of the iron binding sites. The implications of these results for the
      etiopathogenesis of Alzheimer's disease are discussed.

PMID- 15975771
TI  - Electrophysiological correlates of temporal generalization: evidence for a two
      process model of time perception.
AB  - In an event-related potential (ERP) study, brain correlates of temporal
      processing in the range of milliseconds were investigated by means of a
      dissociation paradigm. For this purpose, ten male and ten female subjects
      performed temporal and pitch generalization tasks with uni- and bidimensional
      stimulus variation. With difficulty held constant for both tasks, a larger
      frontally distributed negative slow wave was observed for pitch generalization
      relative to temporal generalization. This ERP pattern was consistent across uni-
      and bidimensional tasks of the present study but in direct contrast to prior ERP
      studies on temporal processing. Furthermore, for both uni- and bidimensional
      temporal tasks, within-task ERP analyses yielded amplitude modulation of centro
      parietal P3b and fronto-central P500 as brain correlates of actively processed
      stimulus duration. Findings were consistent with a two-process model of temporal
      information processing based on a real-time comparison of the presented stimulus
      duration against an internal representation of the standard duration.

PMID- 15975772
TI  - Investigation on dynamic changes of photosynthetic characteristics of 10 wheat
      (Triticum aestivum L.) genotypes during two vegetative-growth stages at water
      deficits.
AB  - Drought is a worldwide problem, seriously influencing plant (crop) productivity.
      Wheat is a stable food for 35% of the world population, and moreover, about 60%
      of land area on the globe belongs to arid and semiarid zone. Wheat drought
      resistance is a multi-gene controlling quantitative character and wheat final
      production in field is realized mainly by physiological regulation under the
      condition of multi-environmental factor interaction. Exploring drought resistance
      physiological mechanisms for different wheat genotypes is of importance to
      finding new drought resistance gene resources and conventional breeding, and the
      basis for wheat drought resistance biotechnological breeding and platform.
      Photosynthesis is the main component for physiological machinery of wheat
      assimilates conversion and wheat production. Investigation on photosynthetic
      characteristics of different wheat genotypes at soil water deficits also has
      other implications for refine physiological regulation of photosynthesis in
      fields and field management of crops in arid and semiarid areas. By pot
      cultivating experiments, investigation of photosynthesis for 10 wheat genotypes
      at seedling stage and tillering stage at soil water deficits (75%FC, 55%FC and
      45%FC, respectively) was conducted. The main results were as followed:
      developmental stages influenced wheat photosynthesis greatly and tillering stage
      played more roles; there were significant difference in the main photosynthetic
      parameters, photosynthesis rate (Photo), stomatal conductance (Cond) and
      transpiration rate (Tr), among 10 wheat genotypes; general photosynthesis and
      drought resistance in different wheat genotypes was related much to their
      domesticated origin soil water environment and selected generations and there was
      a photosynthetic threshold effect in terms of different wheat genotypes at soil
      water deficits.

PMID- 15975773
TI  - Chemical composition of the volatile oil from Cynanchum stauntonii and its
      activities of anti-influenza virus.
AB  - The volatile oil of the roots of Cynanchum stauntonii was examined by gas
      chromatography-mass spectrometry (GC-MS). Thirty-eight constituents were
      identified. (E,E)-2,4-Decadienal, 3-efhyl-4-methypentanol, 5-pentyl-3H-furan-2
      one, (E,Z)-2,4-decadienal and 2(3H)-furanone,dihydro-5-pentyl were found to be
      the major components. The volatile oil exhibited the activities against influenza
      virus in vitro (IC50s=64 microg/ml). In in vivo experiment, it prevented
      influenza virus-induced deaths in a dose-dependent manner.

PMID- 15975774
TI  - Prevalence and underdiagnosis of COPD by disease severity and the attributable
      fraction of smoking Report from the Obstructive Lung Disease in Northern Sweden
      Studies.
AB  - BACKGROUND: There is a lack of epidemiological data on COPD by disease severity.
      We have estimated the prevalence and underdiagnosis of COPD by disease severity
      defined by the British Thoracic Society (BTS) and Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) guidelines. The impact of smoking was evaluated
      by the population attributable fraction of smoking in COPD. METHODS: A random
      sample of 1500 responders of the third postal survey performed in 1996 of the
      Obstructive Lung Disease in Northern Sweden (OLIN) Studies' first cohort (6610
      subjects recruited in 1985) were invited to structured interview and spirometry.
      One thousand two hundred and thirty-seven subjects (82%) performed spirometry.
      RESULTS: The prevalence of mild BTS-COPD was 5.3%, moderate 2.2%, and severe 0.6%
      (GOLD-COPD: mild 8.2%, moderate 5.3%, severe 0.7%, and very severe 0.1%). All
      subjects with severe COPD were symptomatic, corresponding figures among mild COPD
      were 88% and 70% (BTS and GOLD), Subjects with severe BTS-COPD reported a
      physician-diagnosis consistent with COPD in 50% of cases, in mild BTS-COPD 19%,
      while in mild GOLD-COPD only 5% of cases. The major risk factors, age and
      smoking, had a synergistic effect on the COPD-prevalence. The Odds Ratio (OR) for
      having COPD among smokers aged 76-77 years was 59 and 34 (BTS and GOLD) when non
      smokers aged 46-47 was used as reference population. CONCLUSIONS: Most subjects
      with COPD have a mild disease. The underdiagnosis is related to disease-severity.
      Though being symptomatic, only a half of the subjects with severe COPD are
      properly labelled. Smoking and increasing age were the major risk factors and
      acted synergistic.

PMID- 15975775
TI  - COPII-coated vesicles: flexible enough for large cargo?
AB  - Cargo proteins exiting the endoplasmic reticulum en route to the Golgi are
      typically carried in 60-70 nm vesicles surrounded by the COPII protein coat. Some
      secretory cargo assemblies in specialized mammalian cells are too large for
      transport within such carriers. Recent studies on procollagen-I and chylomicron
      trafficking have reached conflicting conclusions regarding the role of COPII
      proteins in ER exit of these large biological assemblies. COPII is no doubt
      essential for such transport in vivo, but it remains unclear whether COPII
      envelops the membrane surrounding large cargo or instead plays a more indirect
      role in transport carrier biogenesis.

PMID- 15975776
TI  - How mitochondria fuse.
AB  - Mitochondrial fusion is unique; no paradigm exists to explain how two sets of
      compositionally distinct membranes become coordinately fused. Genetic approaches
      coupled with in vivo observations of mitochondrial dynamics and morphology have
      identified the machinery involved in mitochondrial fusion but these approaches
      alone yield limited mechanistic insight. The recent recapitulation of
      mitochondrial fusion in vitro has allowed the fusion process to be dissected into
      two mechanistically distinct, resolvable steps: outer membrane fusion and inner
      membrane fusion. Outer membrane fusion requires homotypic trans interactions of
      the ancient dynamin-related GTPase Fzo1, the proton-gradient component of the
      inner membrane electrical potential, and low levels of GTP hydrolysis. Fusion of
      inner membranes requires the electrical component (Deltapsi) of the inner
      membrane electrical potential and elevated levels of GTP hydrolysis. Regulation
      of mitochondrial fusion is likely to involve transcript processing in mammalian
      cells as well as variation in the level of fusion proteins in a given cell;
      slight changes in the electrical potential of the inner membrane may also serve
      to fine-tune fusion rates. Mitochondrial fusion components also serve to protect
      cells against apoptosis through mechanisms that are largely unknown. Resolving
      the mechanism of mitochondrial fusion will provide insight into the role of
      fusion components in apoptosis.

PMID- 15975777
TI  - The dynamic ER: experimental approaches and current questions.
AB  - The endoplasmic reticulum (ER) is an extremely plastic and dynamic organelle. Its
      size and shape can undergo drastic changes to meet changing demands for ER
      related functions, or as a response to drugs or pathogens. Because of the ER's
      key functions in protein and lipid synthesis, this organelle is a hotbed of
      detailed molecular analysis.

PMID- 15975778
TI  - The Golgi apparatus: defining the identity of Golgi membranes.
AB  - The Golgi apparatus is a stack of compartments that serves as a central junction
      for membrane traffic, with carriers moving through the stack as well as arriving
      from, and departing toward, many other destinations in the cell. This requires
      that the different compartments in the Golgi recruit from the cytosol a distinct
      set of proteins to mediate accurate membrane traffic. This recruitment appears to
      reflect recognition of small GTPases of the Rab and Arf family, or of lipid
      species such as PtdIns(4)P and diacylglycerol, which provide a unique "identity"
      for each compartment. Recent work is starting to reveal the mechanisms by which
      these labile landmarks are generated in a spatially restricted manner on specific
      parts of the Golgi.

PMID- 15975779
TI  - Subcompartmentalizing the Golgi apparatus.
AB  - The subcompartmentalized structure of the Golgi apparatus contributes to
      efficient glycosylation in the secretory pathway. Subcompartmentalization driven
      by maturation relies primarily on constant and accurate vesicle-mediated local
      recycling of Golgi residents. The precision of this vesicle transport is
      dependent on the interplay between the key factors that mediate vesicle budding
      and fusion--the coat proteins and the SNARE fusion machinery. These alone,
      however, may not be sufficient to ensure establishment of compartments de novo,
      and additional regulatory mechanisms operate to modify their activity.

PMID- 15975781
TI  - Control of mitochondrial shape.
AB  - Although mitochondria are known to exhibit a wide variety of morphologies in
      different cells, the mechanism by which these shapes are established and
      regulated are largely unknown. Several potential shape-forming proteins have been
      recently identified. Some studies suggest that these proteins control shape by
      mediating attachment of mitochondria to the cytoskeleton, while other studies
      indicate that these proteins form part of a connection between the mitochondrial
      outer and inner membranes. Complicating matters, a recent study raises the
      possibility that one or more of these shape-forming proteins plays a direct role
      in the import and assembly of mitochondrial proteins synthesized in the cytosol.

PMID- 15975780
TI  - Evolving endosomes: how many varieties and why?
AB  - The cell biologist's insight into endosomal diversity, in terms of both form and
      function, has increased dramatically in the past few years. This understanding
      has been promoted by the availability of powerful new techniques that allow
      imaging of both cargo and machinery in the endocytic process in real time, and by
      our ability to inhibit components of this machinery by RNA interference. The
      emerging picture from these studies is of a highly complex, dynamic and adaptable
      endosomal system that interacts at various points with the secretory system of
      the cell.

PMID- 15975782
TI  - The Fab1 phosphatidylinositol kinase pathway in the regulation of vacuole
      morphology.
AB  - Yeast vacuoles are very dynamic structures that must respond to changes in
      extracellular osmolarity by rapidly altering their size, thereby releasing or
      taking up water and ions. Further, the need to accommodate a constant
      biosynthetic influx of membrane and to partition vacuoles during cell division
      necessitates precise regulation of the size and shape of the vacuole. While it is
      has been shown that the lipid kinase Fab1p and its product phosphatidylinositol
      3,5-bisphosphate, and not the mitogen-activated protein kinase Hog1p, are central
      to this regulatory pathway, key effectors still await identification. Atg18p is
      the most recently identified candidate for a Fab1p effector mediating the largely
      uncharacterized processes of vesicle fission and membrane recycling at the
      vacuole.

PMID- 15975783
TI  - Endoplasmic reticulum: one continuous network compartmentalized by extrinsic
      cues.
AB  - The endoplasmic reticulum (ER) is an extensive three-dimensional network that
      stretches from the inner nuclear envelope to the cell cortex with a single,
      continuous membrane and a single, continuous lumen. Yet the ER contains
      specialized regions that carry out unique functions. The question that
      immediately arises is how the ER can be compartmentalized if it is continuous,
      and the answer to this is that cellular landmarks with unique sub-cellular
      distributions impose non-uniformity on the ER from outside, creating structural
      and functional sub-domains of the ER.

PMID- 15975784
TI  - Processing of metallurgical residues by flotation - bench-scale studies on two
      industrial products.
AB  - Resource recovery from two metallurgical residues by flotation was investigated
      applying an electrostatic model to select initial conditions. The first, a
      sulphation roast/water leach residue, was processed to float lead sulphate,
      comparing dodecylamine and xanthate collectors. From the second, a neutralization
      residue, gypsum, was recovered by reverse flotation of ferric hydroxide,
      comparing oleate and sulphonate collectors. In both cases, further upgrading by
      acid leaching was considered.

PMID- 15975785
TI  - Endocrine effects of aromatase inhibitors and inactivators in vivo: review of
      data and method limitations.
AB  - The so-called "third-generation" aromatase inhibitors/inactivators have become
      standard first-line endocrine therapy for postmenopausal women in the metastatic
      setting. In addition, these compounds, administered as monotherapy or in sequence
      with tamoxifen, are likely to become standard adjuvant therapy in most countries
      in the near future. In contrast to the SERMs, aromatase inhibitors may be
      assessed for their biochemical efficacy in vivo either by measuring their ability
      to suppress plasma and tissue estrogen levels or, alternatively, by measuring
      their ability to inhibit the conversion of tracer-labelled androstenedione into
      estrone. While contemporary methods for estrogen measurement (with the exception
      of estrone sulphate) lack the sensitivity to measure plasma estrogen levels
      during treatment with the most potent compounds, in vivo aromatase inhibition can
      be determined with a much better sensitivity. Thus, in a joint program conducted
      by the Royal Marsden Hospital, London and our team in Bergen, we were able to
      reveal profound differences between first- and second-generation aromatase
      inhibitors, causing 50-90% aromatase inhibition, and the three third-generation
      compounds, causing >98% inhibition of total body aromatization.

PMID- 15975786
TI  - Effect of compost temperature on oxygen uptake rate, specific growth rate and
      enzymatic activity of microorganisms in dairy cattle manure.
AB  - Investigations were carried out to find out the relationship between temperature
      and microbial activity in dairy cattle manure composting using oxygen uptake
      rate, specific growth rate and enzymatic activities during autothermal and
      isothermal composting experiments. In autothermal composting, oxygen uptake rate
      and specific growth rate were found to be most intensive in order of 43 degrees
      C, 60 degrees C and 54 degrees C. Isothermal composting at 54 degrees C resulted
      highest levels of enzymatic activity and promoted the volatile solids reduction.
      Based on the maximum enzymatic activity, specific growth rate appeared to be more
      closely linked with microbial activity in compost than with oxygen uptake rate.
      The enhancement of specific growth rate, enzymatic activity and volatile solids
      reduction were induced at 54 degrees C in cattle manure composting.

PMID- 15975788
TI  - Synthesis and antiviral activities of novel N-alkoxy-arylsulfonamide-based HIV
      protease inhibitors.
AB  - A series of novel N-alkoxy-arylsulfonamide HIV protease inhibitors with low
      picomolar enzyme activity and single digit nanomolar antiviral activity is
      disclosed.

PMID- 15975787
TI  - Identification of 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5
      HT2C receptor agonists.
AB  - Synthesis and evaluation of the activity of new 4-methyl-1,2,3,4,10,10a
      hexahydropyrazino[1,2-a]indoles as 5-HT(2C) receptor agonists are described.
      Appropriately substituted, several analogs displayed selectivity against the
      other 5-HT(2) receptor subtypes of 1 order of magnitude or more. Selectivity was
      improved for several compounds versus the lead 1, increasing the therapeutic
      interest in this series of 5-HT(2C) receptor agonists.

PMID- 15975789
TI  - Dibenzodioxocinones--a new class of CETP inhibitors.
AB  - Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4
      methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel
      CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor.
      The compound suffered from very low stability in plasma. Optimisation by partial
      synthesis started from 1 and led to low-nanomolar inhibitors with good stability
      in rat plasma.

PMID- 15975790
TI  - Serum lipids as protective factors for subarachnoid hemorrhage.
AB  - Identification of common serum lipid profiles in patients with subarachnoid
      hemorrhage (SAH) may allow a better understanding of its pathogenesis. We
      conducted a hospital-based case-control study in Japan. One hundred and fifty
      consecutive cases of spontaneous SAH during a 5-year period were examined and
      their lipid profiles assessed. Age- and gender-matched controls were identified
      for each case through random hospital sampling. Median serum total cholesterol
      was 161 mg/dl (range 77-288) in patients with SAH, and 209 mg/dl (134-441) in
      controls (p < 0.001). Median serum triglycerides were 95 mg/dl (range 28-589) in
      SAH and 122 mg/dl (31-371) in controls (p < 0.001). A high serum total
      cholesterol of more than 5.20 mmol/L (200 mg/dl) (odds ratio 0.22 [95% confidence
      interval 0.12-0.40]) and a high serum triglyceride of more than 1.70 mmol/L (150
      mg/dl) (odds ratio 0.29 [95% CI 0.14-0.60]) were independent protective factors
      for SAH. In conclusion, higher values of both serum cholesterol and triglyceride
      may be inversely associated with the occurrence of SAH.

PMID- 15975791
TI  - Third ventricular cavernous haemangioma.
AB  - We report a case of a third ventricular cavernous haemangioma (cavernoma).
      Cavernomas rarely occur within the ventricular system. Only 47 well-documented
      cases have been reported in the literature, 21 of which were located in the third
      ventricle. Cavernomas should be considered in the differential diagnosis of third
      ventricular lesions. Ventriculoscopy is very useful in establishing the
      diagnosis.

PMID- 15975792
TI  - Unstable upper and middle thoracic fractures. Preliminary experience with a
      posterior transpedicular correction-fixation technique.
AB  - A number of conservative and operative approaches have been described for the
      treatment of unstable traumatic upper and middle thoracic fractures. The
      advantage of surgical correction and fixation/fusion lies in its potential to
      restore sagittal and coronal alignment, thereby indirectly decompressing the
      spinal cord. A consecutive series of 8 patients with unstable traumatic upper and
      middle thoracic fractures is reviewed. In all patients, polyaxial pedicle screws
      were inserted bilaterally into the two levels above and below the fracture. Rods
      that were less contoured ("undercontoured") than the regional hyperkyphosis at
      the injured level, were anchored to the caudal four screws. The cranial four
      screws, with the vertebrae to which they were inserted, were then progressively
      pulled posteriorly onto the undercontoured rods with rod reducers, thus
      correcting the hyperkyphosis and anterolisthesis. The mean follow-up was 15
      months. The mean regional kyphosis was 23 degrees preoperatively, 17 degrees
      postoperatively and 18 degrees at follow-up. The mean anterolisthesis was 8 mm
      preoperatively, 1 mm postoperatively and 1 mm at follow-up. No hardware failure
      occurred. Five patients with complete spinal cord injury at presentation made no
      neurological recovery, two patients with incomplete spinal cord injury initially
      (ASIA B), recovered substantially (to ASIA D), and the patients who were
      neurologically intact at presentation remained so.

PMID- 15975793
TI  - Microsurgical interruption of dural arteriovenous fistula at the foramen magnum.
AB  - We report two rare cases of progressive congestive myelopathy caused by dural
      arteriovenous fistulae (DAVF) at the foramen magnum. The first, a 69-year-old
      male with a 2-year history of progressive myelopathy, had symptoms unrecognized
      due to a past history that included spinal caries and congenital dislocation of
      the hip. The second, a 60-year-old male, had a recurrence of the myelopathy three
      months after endovascular occlusion of the DAVF feeding artery. Both patients
      were successfully treated by direct microsurgical interruption of the
      arterialized medullary vein with functional and radiological improvement. The
      clinical manifestations of DAVF at the foramen magnum are nonspecific, mimicking
      those of cervical spondylotic myelopathy or cervical neoplasm. Accurate and early
      diagnosis followed by complete obliteration of the fistula is mandatory to avoid
      permanent neurological deficit.

PMID- 15975794
TI  - Ruptured aneurysm of the posterior spinal artery of the conus medullaris.
AB  - A case of a posterior spinal artery aneurysm of the conus medullaris is
      presented. The patient presented with severe lower back pain with radiation into
      the right leg. Spinal angiography was consistent with a partially thrombosed
      arteriovenous malformation (AVM) or an aneurysm. At operation a partially
      thrombosed aneurysm of the posterior spinal artery was found at the level of
      conus medullaris, which, after review of the literature, is the first case
      treated with total microsurgical excision.

PMID- 15975796
TI  - Encephalocoele-- epidemiological variance in New Zealand.
AB  - Considerable variation in the epidemiology of encephalocoeles throughout the
      world has been described in previous studies. We analysed 46 cases of
      encephalocoele presenting to Auckland and Starship Children's Hospital over the
      last 25 years to determine if our experience differed from that seen in a typical
      Western population, and to determine if there was variation between the different
      racial groups within New Zealand. The overall incidence of encephalocoeles in the
      area serviced by the neurosurgical services of Auckland and Starship Children's
      Hospitals was 1 in 13,418 births. This rate is at the higher end of the incidence
      spectrum compared with previous series. Overall, New Zealand appears to
      demonstrate a typical Western distribution of encephalocoele location. In people
      of Pacific Island descent, both the rate of encephaloceles (1 per 8,873 births)
      and the percentage of sincipital lesions (44%) differed from the rest of the
      population. Additionally, a higher than expected proportion of sincipital
      encephalocoeles was seen in male babies (5:1 male to female ratio). In most other
      regards our population resembles that of western cohorts published in the
      literature.

PMID- 15975795
TI  - Submuscular transposition of the ulnar nerve: review of safety, efficacy and
      correlation with neurophysiological outcome.
AB  - OBJECTIVE: The surgical management of ulnar nerve entrapment at the elbow is a
      controversial topic, with each surgeon believing his/her technique to be the
      best. The authors routinely perform submuscular transposition (SMT) of the ulnar
      nerve to treat entrapment neuropathy at the elbow. The aims of this review are
      (1) to review the results of SMT with respect to safety and complications, (2) to
      compare the efficacy of SMT with other studies previously published, and (3) to
      compare the clinical results with the neurophysiological outcome. METHODS: A
      retrospective review of patients who underwent SMT for ulnar nerve entrapment
      between April 2000 and May 2003 was performed. Forty-five ulnar nerves in 44
      patients were operated, of which 40 nerves were first time operation (primary
      group), and 5 nerves had previously undergone a simple decompressive procedure
      elsewhere (redo group). All patients were graded using the Louisiana State
      University Medical Centre (LSUMC) system for grading of ulnar nerve entrapment.
      Pre- and post-operative nerve conduction studies were performed, and these
      results compared to clinical recovery post-operatively. RESULTS: For the primary
      group, function improved by one grade in 32.5%, two grades in 37.5% and three
      grades in 12.5% of patients. There was no change in 17.5%, and no patient
      deteriorated post-operatively. In the redo group there was improvement of at
      least one grade in 60% of patients. When clinical improvement was compared with
      electrophysiological improvement, no clear correlation was demonstrated.
      CONCLUSION: Submuscular transposition of the ulnar nerve is a safe, effective
      treatment for ulnar nerve entrapment at the elbow. When performed by trained
      peripheral nerve surgeons, good results are achievable for both primary and redo
      surgery.

PMID- 15975797
TI  - Catalytic Pictet-Spengler reactions using Yb(OTf)3.
AB  - The catalytic Pictet-Spengler reactions proceeded in high yields with high
      regioselectivity in the presence of a catalytic amount of Yb(OTf)3 and a
      dehydrating agent at room temperature. High regioselectivities were obtained in
      these reactions, and it is suggested that the reactions proceeded under kinetic
      control.

PMID- 15975798
TI  - Chiral cruciferous phytoalexins: preparation, absolute configuration, and
      biological activity.
AB  - Synthesized by an efficient one-pot spirocyclization method, two chiral
      cruciferous phytoalexins, 1-methoxyspirobrassinin (2) and 1-methoxyspirobrassinol
      methyl ether (4a), were prepared through optical resolution using the chiral HPLC
      method of corresponding racemates. The absolute configuration of natural (+)-2
      was elucidated as R by using the direct comparison of ECD and VCD spectra with
      those of known (S)-(-)-spirobrassinin (1). Another chiral phytoalexin, (-)-4a,
      had its absolute configuration 2R,3R elucidated through the comparison of
      observed and calculated VCD. Interestingly, the absolute configurations of
      natural (S)-(-)-spirobrassinin (1) and (R)-(+)-1-methoxyspirobrassinin (2) were
      opposite of each other, even though their structures are almost similar, with the
      exception of an N-methoxy group. A significant difference in the
      antiproliferative activity between (2R,3R)-(-) and (2S,3S)-(+)-4a was observed.

PMID- 15975799
TI  - Insight into 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as peripheral
      benzodiazepine receptor ligands: synthesis, biological evaluation and 3D-QSAR
      investigation.
AB  - The present paper reports the synthesis and binding studies of new 2
      phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as selective Peripheral
      Benzodiazepine Receptor (PBR) ligands. The variability of substituents at the 3
      position was investigated and a 3D-QSAR model was proposed to evaluate the effect
      of different substitutions on the acetamide moiety. In addition, a subset of the
      novel compounds showing high affinity for PBR was tested for their ability to
      modulate the steroid biosynthesis in C6 glioma cells.

PMID- 15975801
TI  - Ultrastructure of mature spermatozoids in the fern Asplenium onopteris L.
AB  - Asplenium onopteris L. spermatozoids are 8-8.5 microm long in the form of spirals
      with 4.5 turns. They have about 50 flagella. The nucleus occupies the last three
      posterior turns. Chromatin is partly honeycomb-shaped and partly highly
      condensed. An electron transparent space crossed by dense fibers delimits the
      condensed chromatin. Here, the nuclear membranes are closely apposed without any
      space between them and the plasmalemma often invaginates among elements of the
      microtubular ribbon, connecting with the outer nuclear membrane. An electron
      opaque body apparently links and anchors all anterior spermatozoid components.
      The cytoplasm contains plastids with starch grains, (lipid) bodies and different
      membrane systems, which are presumably plasmalemma derivatives involved in a
      process of cytoplasmic reduction.

PMID- 15975800
TI  - Efficient synthesis of fluorothiosparfosic acid analogues with potential
      antitumoral activity.
AB  - In this paper, we describe a short synthesis of N-(phosphonoacetyl)-L-aspartate
      (PALA) analogues. The mono- and difluorinated thioacetamide precursors were
      prepared in one step from methyl (diethoxyphosphono)di- and
      monofluoromethyldithioacetates 8 and 11 as starting materials. Antiproliferating
      properties on a L1210 strain and ATCase inhibition of these new compounds are
      disclosed. ThioPALA(FF) 5c showed a remarkable cytotoxic activity towards murine
      leukemia L1210, when used as tetraester.

PMID- 15975802
TI  - Morphology of Bufo ictericus integument (Amphibia, Bufonidae).
AB  - Bufo ictericus integument was investigated by stereoscopic, low vacuum scanning
      electron microscopy, transmission electron microscopy and light microscopy. The
      studies revealed, that the dorsal integument surface is rougher than ventral.
      Three types of projections are visualized: larger rounded verrucae, smaller
      conical cornified tubercles, and conical short spines. Prominent verrucae are
      observed on the dorsal surface, being flatter on the ventral surface. The
      tubercles are visualized only on the dorsal surface. The verrucae are separated
      by grooves that may contribute spreading and retention of the glandular secretion
      upon the integument. The pattern of the epidermal grooves is also important for
      water distribution, protecting the animal against desiccation. The epidermis is
      composed of a stratified epithelium with intraepithelial blood vessels, where
      keratinocytes predominate, but flask cells, and Merkel cells also occur. In the
      spongious dermis, cutaneous glands are visualized. The compact dermis is a series
      of alternating layers of bundles of collagenous fibers, and between spongious and
      compact dermis there are basophilic areas that correspond to Eberth-Katschenko
      layer. The dorsal and the ventral surfaces of B. ictericus are morphologically
      distinct. The integument structure is related to the physiology of each surface
      and represents an adaptation to habitat, reflecting a lifestyle of the animal.

PMID- 15975803
TI  - Assessing the interaction between Helicobacter pylori and human neutrophils by
      freeze-fracture replica labeling.
AB  - We recently introduced a freeze-fracture replica labeling method adapted to
      studies of bacterial envelopes. This report describes a further development of
      this detergent-digested freeze-fracture replica labeling technique, thus more
      exactly the conception of this explicit methodology for visualization of bacteria
      host cell interactions. Our experimental model employs human neutrophils and the
      gastric pathogenic bacterium Helicobacter pylori. The phagocytic process
      performed by the neutrophils represents a crucial element of the host defense
      system against invading microorganisms, and by so doing, it allows direct
      observation of the interplay between bacteria and host cells at an
      ultrastructural level. The here launched methodology can be used as a tool to
      investigate the events taking place between pathogenic microbes and phagocytes,
      as well as for pinpoint targeting of other cell-cell communications in the field
      of cell biology.

PMID- 15975804
TI  - D-D neutron generator development at LBNL.
AB  - The plasma and ion source technology group in Lawrence Berkeley National
      Laboratory is developing advanced, next generation D-D neutron generators. There
      are three distinctive developments, which are discussed in this presentation,
      namely, multi-stage, accelerator-based axial neutron generator, high-output co
      axial neutron generator and point source neutron generator. These generators
      employ RF-induction discharge to produce deuterium ions. The distinctive feature
      of RF-discharge is its capability to generate high atomic hydrogen species, high
      current densities and stable and long-life operation. The axial neutron generator
      is designed for applications that require fast pulsing together with medium to
      high D-D neutron output. The co-axial neutron generator is aimed for high neutron
      output with cw or pulsed operation, using either the D-D or D-T fusion reaction.
      The point source neutron generator is a new concept, utilizing a toroidal-shaped
      plasma generator. The beam is extracted from multiple apertures and focus to the
      target tube, which is located at the middle of the generator. This will generate
      a point source of D-D, T-T or D-T neutrons with high output flux. The latest
      development together with measured data will be discussed in this article.

PMID- 15975805
TI  - Effects of threshold voltage variability on the characteristics of high
      sensitivity metal-oxide-semiconductor dosimeters.
AB  - The consequence of the variability of the threshold voltage of high sensitivity
      metal-oxide-semiconductor (MOS) dosimeters on the accuracy of the measured dose
      is presented.

PMID- 15975806
TI  - Response of the ascorbate-glutathione cycle to re-aeration following hypoxia in
      lupine roots.
AB  - The response of the enzymes and metabolites of the ascorbate-glutathione pathway
      to oxidative stress caused by re-aeration following hypoxia was studied in roots
      of hydroponically grown lupine (Lupinus luteus L. cv. Juno) seedlings. Lupine
      roots were deprived of oxygen by subjecting them to hypoxia for 48 and 72 h and
      then re-aerated for up to 4 h. An increased content of total ascorbate was
      observed in lupine roots immediately after hypoxia, whereas total glutathione
      level decreased. However, a significant increase in the reduced forms of both
      metabolites was found directly after hypoxia. Re-admission of oxygen caused the
      decrease of the ratios of reduced to oxidized forms of ascorbate and glutathione,
      indicating oxidative stress. While monodehydroascorbate reductase (MDHAR, EC
      1.6.5.4) activity remained unaltered during re-aeration the increase in
      activities of ascorbate peroxidase (APX, EC 1.11.1.11) and glutathione reductase
      (GR, EC 1.6.4.2) was observed 30 min after transfer from hypoxic condition.
      Dehydroascorbate reductase (DHAR, EC 1.8.5.1) activity approached the control
      level during a whole re-aeration period. Native gel electrophoresis combined with
      specific activity staining revealed seven isoforms of APX, five isoforms of GR
      and three different proteins with DHA reductase activity in roots extracts.
      However, immediately after hypoxic treatment APX-5 isoform and GR-1 isoform were
      not observed in roots. This experimental system was also used to investigate
      superoxide anion level in roots utilizing the superoxide anion-specific indicator
      dihydroethidium (DHE). Intense DHE-derived fluorescence was found in re-aerated
      root tips as compared to control roots, indicating that re-aeration induced
      superoxide anion production in hypoxically pretreated roots.

PMID- 15975807
TI  - Mandibular osteoma in the encephalocraniocutaneous lipomatosis.
AB  - INTRODUCTION: Encephalocraniocutaneous lipomatosis is a rare congenital disorder
      characterized by an abnormal development of adipose tissue, and is of unknown
      pathogenesis. Catherine Haberland and Maurice Perou first diagnosed this disorder
      in 1970. To our knowledge, approximately 25 patients have been reported with this
      diagnosis but so far, only 1 patient has been reported in Poland by Roszkowski
      and Dabrowski in 1997. At that time she was a 13-year-old girl, who was
      neurosurgically treated. CASE REPORT: The authors followed the same patient (now
      21 years old), who was referred to the Department of Cranio-Maxillofacial Surgery
      of the Medical University of Lodz for osteoma of the mandible. Partial resection
      of the mandible was performed on account of the size of the lesion. The mandible
      was reconstructed by an iliac crest bone graft fixed by 2 titanium plates. The
      surgical procedure is described. CONCLUSION: Encephalocraniocutaneous lipomatosis
      is a very rare syndrome. Most of the cases described in the literature presented
      lipomas of the skin with neurological and ophthalmological disturbances. Only a
      few authors described jaw tumours and no information was found on such big
      osteomas to this syndrome.

PMID- 15975808
TI  - Treatment of osteomas located between the anterior cranial base and the face.
AB  - OBJECTIVE: Osteomas located on the border between the anterior cranial base and
      the facial region are benign, often asymptomatic and usually slow growing. They
      may cause different complications depending on the part of the central nervous or
      visual systems which they affect. MATERIAL AND METHODS: Between 1997 and 2002,
      four patients were treated at the 1st Department of Maxillofacial Surgery of the
      Medical University of Warsaw for osteomas located at the border of the anterior
      cranial base. In all patients a radical surgical removal of the tumour was
      performed via bifrontal craniotomy, with an extradural approach to the anterior
      cranial fossa. The resulting defects were repaired with autologous bone grafts.
      RESULTS: The post-operative results were good regarding morphological, functional
      and aesthetic outcome. Two of the four patients are described to illustrate the
      surgical treatment.

PMID- 15975809
TI  - Untreated 'blow-in' fracture of the orbital floor causing a mucocele: report of
      an unusual late complication.
AB  - BACKGROUND: Several severe complications have been described with blow-in
      fractures. Therefore, immediate surgical treatment of these fractures has been
      recommended. To date, there is only minimal knowledge on long-term complications
      of blow-in fractures that have remained untreated. The present case report
      describes a late complication of an untreated blow-in fracture of the orbital
      floor. CASE: A 37-year-old male was involved in a car accident 16 years before.
      At that time, a non-dislocated midfacial fracture was diagnosed and remained
      untreated because of the lack of clinical symptoms. Four months before surgery an
      exophthalmos of the left globe began to develop. CT examination revealed a
      consolidated blow-in fracture of the left orbital floor and an opaque mass around
      the dislocated bony fragments. By an infraorbital approach the bony fragments and
      the surrounding mass were removed. Histological examination of the removed
      material revealed a cystic structure lined with respiratory epithelium.
      Therefore, the diagnosis 'post-traumatic mucocele in the orbit caused by
      dislocated respiratory epithelium from the maxillary sinus' was made. CONCLUSION:
      Even if blow-in fractures do not cause complications immediately after trauma,
      late complications like mucoceles can occur after several symptom-free years.
      Therefore, early reconstruction should be intended even in asymptomatic cases of
      blow-in fractures with minimal displacement of the bony fragments.

PMID- 15975810
TI  - A surgical simulator for planning and performing repair of cleft lips.
AB  - The objective of this project was to develop a computer-based surgical simulation
      system for planning and performing cleft lip repair. This system allows the user
      to interact with a virtual patient to perform the traditional steps of cleft-lip
      repair (rotation-advancement technique). MATERIALS AND METHODS: The system
      interfaces to force-feedback (haptic) devices to track the user's motion and
      provide feedback during the procedure, while performing real-time soft-tissue
      simulation. An 11-day-old unilateral cleft lip, alveolus and palate patient was
      previously CT scanned for ancillary diagnostic purposes using standard imaging
      protocols and 1mm slices. High-resolution 3D meshes were automatically generated
      from this data using the ROVE software developed in-house. The resulting 3D
      meshes of bone and soft tissue were instilled with physical properties of soft
      tissues for purposes of simulation. Once these preprocessing steps were
      completed, the patient's bone and soft tissue data are presented on the computer
      screen in stereo and the user can freely view, rotate, and otherwise interact
      with the patient's data in real time. The user is prompted to select anatomical
      landmarks on the patient's data for preoperative planning purposes, then their
      locations are compared against that of a 'gold standard' and a score, derived
      from their deviation from that standard and time required, is generated. The user
      can then move a haptic stylus and guide the motion of the virtual cutting tool.
      The soft tissues can thus be incised using this virtual cutting tool, moved using
      virtual forceps, and fused in order to perform any of the major procedures for
      cleft lip repair. Real-time soft tissue deformation of the mesh realistically
      simulates normal tissues and haptic-rate (>1 kHz) force-feedback is provided. The
      surgical result of the procedure can then be immediately visualized and the
      entire training process can be repeated at will. A short evaluation study was
      also performed. Two groups (non-medical and plastic surgery residents) of six
      persons each performed the anatomical marking task of the simulator four times.
      RESULTS: Results showed that the plastic surgery residents scored consistently
      better than the persons without medical background. Every person's score
      increased with practice, and the length of time needed to complete the 11
      markings decreased. The data was compiled and showed which specific markers
      consistently took users the longest to identify as well as which locations were
      hardest to accurately mark. CONCLUSION: These findings suggest that the simulator
      is a valuable training tool, giving residents a way to practice anatomical
      identification for cleft lip surgery without the risks associated with training
      on a live patient. Educators can also use the simulator to examine which markers
      are consistently problematic, and modify their training to address these needs.

PMID- 15975811
TI  - Adult congenital lung disease.
AB  - Congenital lung anomalies are increasingly diagnosed in adults, because they are
      missed in childhood, or as a consequence of incomplete resections at a younger
      age. They have unique manifestations, often mimic other thoracic pathology, and
      can present acutely and necessitate emergent evaluation and management.
      Misdiagnosis is common. This article deals with the patterns of presentation,
      clinical and radiological diagnosis, and the management of these disorders in
      adults. The lesions analysed include congenital cystic adenomatoid malformation,
      sequestration, congenital lobar emphysema and bronchogenic cysts. It is important
      to include these malformations in the differential diagnosis of adult thoracic
      pathology and to understand the modes of presentation, potential complications
      and management strategies. The radiological diagnosis is reliably made by
      computed tomography and/or magnetic resonance imaging. The potential for
      malignancy in these lesions is an important consideration. The management of
      asymptomatic lesions was considered controversial, but more lesions are now
      resected early, in recognition of the potential for subsequent complications.
      Complete resection is recommended. In contradistinction to childhood
      malformations, these lesions are more amenable to thoracoscopic resections,
      provided they are completely benign. Congenital lung malformations call for well
      organized cooperation between paediatric and adult pulmonologists to ensure a
      smooth medical transition from childhood to adulthood.

PMID- 15975812
TI  - Chronic obstructive pulmonary disease as a prognostic factor in non-small cell
      lung cancer.

PMID- 15975813
TI  - Three-dimensional demonstration of the collateral circulation to the artery of
      Adamkiewicz via internal thoracic artery with 16-row multi-slice CT.

PMID- 15975814
TI  - Azygous vein anomaly in a lung cancer patient.

PMID- 15975815
TI  - Platelet function tests predict bleeding and thrombotic events after off-pump
      coronary bypass grafting.

PMID- 15975817
TI  - Neonatal repair of tetralogy of Fallot results in improved pulmonary artery
      development without increased need for reintervention.
AB  - OBJECTIVE: Despite a continuous improvement in operative outcome the optimal
      timing for the repair of tetralogy of Fallot (TOF) remains controversial. The
      purpose of this study was to evaluate the results following neonatal repair of
      TOF and the need for reintervention associated with this strategy. METHODS:
      Retrospective review of 66 consecutive patients with TOF and confluent pulmonary
      arteries, who underwent repair immediately after diagnosis. Group I (n=46) had a
      median age of 5 days (1-29) and Group II (n=20) had a median age of 56 days (32
      270). A transventricular approach was used in all cases, and 58/66 (88%) patients
      received a transannular patch. The median follow-up interval was 35 months (1
      79). RESULTS: There were three early deaths (4.5%) and no late deaths for an
      actuarial survival rate of 95.4% at 1 and 5 years. Univariate analysis of patient
      and procedural variables demonstrated that early mortality was only influenced by
      associated non-cardiac conditions (P=0.04). At median interval of 9.8 months (3
      41), 12 patients required additional intervention. During the follow-up period, a
      significant increase in Nakata index was observed only among neonates. Freedom
      from reintervention at 1 month, 1 and 5 years was: 100, 84.2 and 81% in group I
      and 100, 84, 78.9% in group II. Surgical weight below 2.5 kg (P<0.001), low
      arterial saturation in the early postoperative period (P=0.04) and small
      preoperative branch pulmonary artery size (<0.01) were associated with need for
      reintervention during follow-up. CONCLUSIONS: Elective repair of TOF in neonates
      with confluent central pulmonary arteries has excellent results in the absence of
      significant associated non-cardiac conditions. While enhancing the development
      and growth of the pulmonary arteries, neonatal repair affords a freedom from
      reintervention no different from patients repaired during infancy. Preoperative
      weight < 2.5 kg and small left pulmonary artery size are associated with higher
      incidence reintervention during follow-up.

PMID- 15975818
TI  - Streptozotocin-induced diabetic nephropathy in rats: the role of inflammatory
      cytokines.
AB  - The role of inflammatory cytokines in the pathogenesis of diabetic nephropathy
      has been studied in streptozotocin-induced diabetic rats. Rat kidneys were
      examined by light and electron microscopy and kidney homogenates were also
      analyzed by Western blot and flow cytometry for the expression of markers of
      inflammation namely, CD4+ and CD8+ T cells, macrophages, MHC classes I and II,
      the proinflammatory cytokines tumor necrosis factor-alpha, interferon-gamma and
      nitric oxide (NO). Light and electron microscope examination revealed
      infiltration of mononuclear cells throughout the renal parenchyma, with the
      glomeruli being more severely affected especially at 8 months after disease
      induction. Western blot and flow cytometric analyses revealed the infiltrating
      cells to be CD4+ T cells, CD8+ T cells and macrophages. Western blot analyses
      also revealed increased expression of the proinflammatory and Th1 cytokines tumor
      necrosis factor-alpha, interferon-gamma as well as nitric oxide. Using flow
      cytometry, we have shown that the difference in expression of CD4+ T cells in
      control and diabetic kidneys is more significant at 1 month than at 8 months,
      while expression of CD8+ T cells is more significant at 8 months. We speculate
      therefore that diabetic nephropathy is probably initiated and driven by a Th1
      process. CD8+ T cells, however, become more significant at later stages of the
      disease when tissue loss is evident. Since NO induction also occurs only after 8
      months, we hypothesize that NO might be significant for the later stages of the
      disease. Our data implicate inflammation in the pathogenesis of diabetic
      nephropathy in view of the overexpression of the proinflammatory cytokines TNF
      alpha and IFN-gamma and the cells that secrete them in the early and late phases
      of the disease.

PMID- 15975819
TI  - Selective induction of interleukin-8 expression in metastatic melanoma cells by
      transforming growth factor-beta 1.
AB  - Interleukin (IL)-8 and transforming growth factor (TGF)-beta1 are proangiogenic
      factors overexpressed in advanced human melanoma. We investigated the effects of
      TGF-beta1 on IL-8 expression in the well-characterized A375 human melanoma
      system. We demonstrated by enzyme-linked immunoassay and Northern blot analysis
      that TGF-beta1 selectively induced IL-8 expression, at both protein and mRNA
      levels, in highly metastatic A375SM cells but not cells of their poorly
      metastatic parental line A375P. Transient transfection with luciferase reporter
      gene constructs revealed that TGF-beta1 activated IL-8 promoter activity in
      A375SM cells but not A375P cells. Studies with progressive 5' deletion constructs
      and site-specific mutations demonstrated that a construct containing -133 to +44
      of the 5'-flanking sequence was necessary and sufficient for maximal TGF-beta1
      induced transcription response and that TGF-beta1-induced activation of IL-8
      promoter depended on AP-1 (-126 to -120 bp), NF-kappaB (-94 to -71 bp), and C/EBP
      like factor NF-IL6 (-94 to -81 bp) in this region. Interestingly, both A375P and
      A375SM cells expressed type I and type II TGF-beta receptors and TGF-beta1
      induced the nuclear translocation of Smad3 protein in both A375P and A375SM
      cells. Moreover, both A375P and A375SM cells were susceptible to TGF-beta1
      induced growth inhibition. Our data thus demonstrated that TGF-beta1 selectively
      induced IL-8 expression in highly metastatic A375SM melanoma cells. This TGF
      beta1-induced IL-8 expression could be an amplification cascade responsible for
      overexpression of IL-8 in human melanoma and one of potential mechanisms by which
      TGF-beta1 promotes angiogenesis, growth, and metastasis of human melanoma.

PMID- 15975820
TI  - IL-17 reduces TNF-induced Rantes and VCAM-1 expression.
AB  - Functional diversity of the memory T-cell-derived cytokine IL-17 was explored at
      the receptor level. IL-17 inhibited TNF-induced chemokine Rantes expression in
      human synovial fibroblasts and mouse lung fibroblasts. This inhibitory activity
      of IL-17 (IC50=0.2 ng/ml) was 6-fold more potent than its stimulatory activity on
      TNF-alpha-induced IL-6 secretion (ED50=1.2 ng/ml), measured in the same cells. IL
      17 also inhibited the TNF-mediated expression of adhesion molecule VCAM-1, and
      the NF-kappaB binding to the VCAM-1 promoter-specific site, along with the
      inhibitor of NF-kappaB, IkappaB-beta. Neutralization of the human IL-17 receptor
      (IL-17R) by M202 antibody competitively reverses the IL-17-induced IL-6
      upregulation. However, M202 only partially affected the inhibitions by IL-17.
      Yet, IL-17R was essential for the Rantes inhibition, as assessed in lung-derived
      fibroblasts from IL-17R gene deficient mice. Therefore, inhibitory and
      stimulatory functions of IL-17 involve receptor IL-17R but show distinct dose
      responses and in turn different sensitivities to an IL-17R antagonizing antibody.

PMID- 15975821
TI  - Acute effects of tacrolimus (FK506) on left ventricular mechanics.
AB  - Tacrolimus (FK506) is a macrolide antibiotic used to minimize transplant
      rejections. Several macrolides affect ventricular function, but the effects of
      tacrolimus are unknown. This study evaluated acute effects of escalating doses of
      tacrolimus on heart rate (HR), left ventricular inotropy, lusitropy, preload (end
      diastolic short axis radius on a 2D directed M-mode echocardiogram), and
      afterload (product of end-diastolic radius and diastolic arterial pressure
      divided by end-diastolic wall thickness) in anesthetized dogs. Tacrolimus at
      0.025 mg kg(-1) increased HR and inotropy with continued escalation up to a dose
      of 0.1 mg kg(-1) (p<0.01). Conversely, tacrolimus at 0.025 mg kg(-1) decreased
      lusitropy and preload, which never achieved steady states (p<0.05). Afterload
      tended to increase between doses of 0.0125 and 0.025 mg kg(-1), and tended to
      decrease at higher doses, achieving baseline at a dose of 0.1 mg kg(-1).
      Tacrolimus significantly prolonged the QT interval (QTc) between doses of 0.0125
      (p<0.05) and 0.1mg kg(-1) (p<0.001). These effects are consistent with altered
      calcium kinetics leading to increased cytosolic calcium. Tacrolimus at a
      clinically relevant dose of 0.1 mg kg(-1) possesses profound, acute effects on
      left ventricular mechanics, suggesting that cardiovascular monitoring may be
      necessary in tacrolimus-treated patients. Potential adverse effects include
      myocardial stiffness, transient increase in systemic arterial pressure, and
      tendency for ventricular arrhythmia.

PMID- 15975822
TI  - Insulin sensitization of MAP kinase signaling by fibroin in insulin-resistant
      Hirc-B cells.
AB  - Fibroin has been shown to enhance insulin-stimulated glucose uptake in 3T3-L1
      adipocytes, and the mechanism underlying the fibroin effect focused on
      phosphatidylinositol 3-kinase (PI 3-K) pathway has been reported. In the present
      study, for defining the insulin-sensitizing effects of fibroin synthetically, we
      have used the Hirc-B cells which are rat fibroblasts over-expressing wild-type
      human insulin receptors to investigate the insulin-stimulation of mitogen
      activated protein (MAP) kinase signaling cascades. Cultivation of Hirc-B cells in
      high-glucose medium for 6 days led to an insulin-resistant state in which insulin
      stimulated DNA synthesis was blocked completely. Chronic exposure to fibroin for
      16 h markedly recovered DNA synthesis in insulin-resistant cells. Development of
      insulin resistance caused a reduction of c-Jun N-terminal kinase (JNK)
      phosphorylation, which was also recovered by fibroin exposure. Fibroin sensitized
      the insulin-stimulated c-Jun accumulation and phosphorylation in insulin
      resistant cells. In the time course for c-Jun accumulation, fibroin had a
      vanadate-like effect. Further, fibroin was shown to delay the degradation of c
      Jun. It is suggested that fibroin may sensitize insulin action by blocking JNK
      dephosphorylation caused by MAP kinase phosphatase-1 (MKP-1).

PMID- 15975823
TI  - The role of esterification on detection of protonated and deprotonated peptide
      ions in matrix assisted laser desorption/ionization (MALDI) mass spectrometry
      (MS).
AB  - Esterification was used to investigate how introduction of aliphatic chains
      within the peptide structure affects the MALDI response of ions analyzed in both
      polarity regimes. In binary mixtures containing equimolar amounts of a peptide
      with its correspondent alkyl ester, derivatization of the carboxylic groups has
      the tendency to increase MALDI detection of the modified protonated peptide ions.
      This positive effect on ion yield is more pronounced when longer alcohols are
      employed. In negative mode, the situation is antithetic and esterification
      produces a deleterious effect on the ion yield of the corresponding deprotonated
      species. From the data reported here we postulate that modifications of the
      acidic character of peptides prevent formation of anionic species under MALDI
      analysis. Furthermore, suppression of the formation pathway for anions alters the
      overall number of molecules which can undergo protonation. This results in an
      increased ion yield for the protonated esters.

PMID- 15975824
TI  - Three-dimensional tissue culture models in cancer biology.
AB  - Three-dimensional (3D) tissue culture models have an invaluable role in tumour
      biology today providing some very important insights into cancer biology. As well
      as increasing our understanding of homeostasis, cellular differentiation and
      tissue organization they provide a well defined environment for cancer research
      in contrast to the complex host environment of an in vivo model. Due to their
      enormous potential 3D tumour cultures are currently being exploited by many
      branches of biomedical science with therapeutically orientated studies becoming
      the major focus of research. Recent advances in 3D culture and tissue engineering
      techniques have enabled the development of more complex heterologous 3D tumour
      models.

PMID- 15975825
TI  - Matrigel: basement membrane matrix with biological activity.
AB  - The basement membrane extracellular matrix contacts epithelial, endothelial, fat
      and smooth muscle cells. Because this extracellular matrix is so thin, it had
      been hard to study its composition, structure, and function. An extract of a
      tumor was found to contain all of the components present in basement and to be
      very biologically active. This extract, termed Matrigel, Cultrex, or EHS matrix,
      promotes cell differentiation, and is used to measure the invasive activity of
      tumor cells. In vivo, it is used for measuring angiogenic inhibitors and
      stimulators, to improve graft survival, repair damaged tissues, and increase
      tumor growth.

PMID- 15975826
TI  - Safety testing for neurovirulence of novel live, attenuated flavivirus vaccines:
      infant mice provide an accurate surrogate for the test in monkeys.
AB  - Current requirements for control of live viral vaccines, including yellow fever
      17D, produced from potentially neurotropic wild-type viruses include tests for
      neurovirulence in nonhuman primates. We have used yellow fever 17D virus as a
      live vector for novel flavivirus vaccines (designated ChimeriVax) against dengue,
      Japanese encephalitis (JE), and West Nile (WN) viruses. For control of these
      vaccines, it would be preferable to substitute a test in mice for the test in a
      higher species (monkeys). In this study, we compare the neurovirulence of
      ChimeriVax vaccine candidates in suckling mice inoculated by the intracerebral
      (IC) route with graded doses of the test article or yellow fever 17D vaccine as a
      reference control. Mortality ratio and survival distribution are the outcome
      measures. The monkey safety test is performed as described for control of yellow
      fever vaccines. In both mice and monkeys, all chimeric vaccines were
      significantly less neurovirulent than yellow fever 17D vaccine. The test in
      suckling mice discriminated between strains of two different vaccines (ChimeriVax
      JE and ChimeriVax-DEN1) differing by a single amino acid change, and was more
      sensitive for detecting virulence differences than the test in monkeys. The
      results indicate that the suckling mouse test is simple to perform, highly
      sensitive and, with appropriate validation, could complement or possibly even
      replace the neurovirulence component of the monkey safety test. The test in
      infant mice is particularly useful as a means of demonstrating biological
      consistency across seed virus and vaccine lots.

PMID- 15975827
TI  - Blood bank produced fibrin sealant and bacterial contamination.

PMID- 15975828
TI  - Detecting and adjusting for artifacts in fMRI time series data.
AB  - We present a new method to detect and adjust for noise and artifacts in
      functional MRI time series data. We note that the assumption of stationary
      variance, which is central to the theoretical treatment of fMRI time series data,
      is often violated in practice. Sporadic events such as eye, mouth, or arm
      movements can increase noise in a spatially global pattern throughout an image,
      leading to a non-stationary noise process. We derive a restricted maximum
      likelihood (ReML) algorithm that estimates the variance of the noise for each
      image in the time series. These variance parameters are then used to obtain a
      weighted least squares estimate of the regression parameters of a linear model.
      We apply this approach to a typical fMRI experiment with a block design and show
      that the noise estimates strongly vary across different images and that our
      method detects and appropriately weights images that are affected by artifacts.
      Furthermore, we show that the noise process has a global spatial distribution and
      that the variance increase is multiplicative rather than additive. The new
      algorithm results in significantly increased sensitivity in the ability to detect
      regions of activation. The new method may be particularly useful for studies that
      involve special populations (e.g., children or elderly) where sporadic, artifact
      generating events are more likely.

PMID- 15975829
TI  - A previously unrecognized radiation of ranid frogs in Southern Africa revealed by
      nuclear and mitochondrial DNA sequences.
AB  - In sub-Saharan Africa, amphibians are represented by a large number of endemic
      frog genera and species of incompletely clarified phylogenetic relationships.
      This applies especially to African frogs of the family Ranidae. We provide a
      molecular phylogenetic hypothesis for ranids, including 11 of the 12 African
      endemic genera. Analysis of nuclear (rag-1, rag-2, and rhodopsin genes) and
      mitochondrial markers (12S and 16S ribosomal RNA genes) provide evidence for an
      endemic clade of African genera of high morphological and ecological diversity
      thus far assigned to up to five different subfamilies: Afrana, Cacosternum,
      Natalobatrachus, Pyxicephalus, Strongylopus, and Tomopterna. This clade has its
      highest species diversity in southern Africa, suggesting a possible biogeographic
      connection with the Cape Floral Region. Bayesian estimates of divergence times
      place the initial diversification of the southern African ranid clade at
      approximately 62-85 million years ago, concurrent with the onset of the radiation
      of Afrotherian mammals. These and other African ranids (Conraua, Petropedetes,
      Phrynobatrachus, and Ptychadena) are placed basally within the Ranoidae with
      respect to the Eurasian groups, which suggests an African origin for this whole
      epifamily.

PMID- 15975830
TI  - Multigene phylogeny of the Old World mice, Murinae, reveals distinct geographic
      lineages and the declining utility of mitochondrial genes compared to nuclear
      genes.
AB  - Despite its great diversity and biomedical importance, the rodent subfamily
      Murinae is poorly resolved phylogenetically. We present the first cladistic
      analysis sampling multiple representatives of most major groups based on DNA
      sequence for three nuclear (GHR, RAG1, and AP5) and one mitochondrial (COII and
      parts of COI and ATPase 8) fragments. Analyzed separately, the four partitions
      agree broadly with each other and the combined analysis. The basal split is
      between a clade of Philippine Old Endemics and all remaining murines. Within the
      latter, rapid radiation led to at least seven geographically distinct lineages,
      including a Southeast Asian Rattus clade; a diverse Australo-Papuan and
      Philippine clade; an African arvicanthine group including the otomyines; an
      African Praomys group; and three independent genera from Africa and Asia, Mus,
      Apodemus, and Malacomys. The murines appear to have originated in Southeast Asia
      and then rapidly expanded across all of the Old World. Both nuclear exons provide
      robust support at all levels. In contrast, the bootstrap proportions from
      mitochondrial data decline rapidly with increasing depth in the tree, together
      suggesting that nuclear genes may be more useful even for relatively recent
      divergences (< 10MYA).

PMID- 15975831
TI  - Molecular phylogeny of basal gobioid fishes: Rhyacichthyidae, Odontobutidae,
      Xenisthmidae, Eleotridae (Teleostei: Perciformes: Gobioidei).
AB  - Morphological character analyses indicate that Rhyacichthyidae, Odontobutidae,
      Eleotridae, and Xenisthmidae are the basal families within the perciform suborder
      Gobioidei. This study uses DNA sequence data to infer the relationships of genera
      within these families, as well as determine the placement of more derived
      gobioids (family Gobiidae) and the identity of the outgroup to Gobioidei.
      Complete sequences of the mitochondrial ND1, ND2, COI, and cyt b genes (4397 base
      pairs) are analyzed for representatives of 27 gobioid genera and a variety of
      perciform and scorpaeniform outgroup candidates; the phylogeny is rooted with a
      beryciform as a distal outgroup. The single most parsimonious tree that results
      indicates that, of the outgroups sampled, the perciform family Apogonidae is most
      closely related to Gobioidei. Gobioidei is monophyletic, and Rhyacichthys aspro
      is the most basal taxon. The remainder of Gobioidei is resolved into clades
      corresponding to the families Odontobutidae (plus Milyeringa) and
      Eleotridae+Xenisthmidae+Gobiidae. Within Eleotridae, the subfamily Butinae (minus
      Milyeringa) is paraphyletic with respect to Gobiidae, and Eleotrinae is
      paraphyletic with respect to Xenisthmidae. Other than these groupings, the
      primary disagreement with the current morphology-based classification is that the
      molecular data indicate that the troglodytic Milyeringa should be placed in
      Odontobutidae, not Butinae, although support for this placement is weak. The most
      basal lineage of Gobioidei is known from the freshwaters of the Indo-Pacific,
      with marine-dwelling lineages arising several times independently in the group.
      The phylogeny also indicates that different gobioid lineages are distributed in
      Asia, Africa, Madagascar and the Neotropics. Five sister pairs of basal gobioid
      species inhabit Atlantic and Pacific drainages of Panama, with widely varying
      divergences.

PMID- 15975832
TI  - Nonclinical proarrhythmia models: predicting Torsades de Pointes.
AB  - Prolongation of the QT interval and the cardiac action potential have been linked
      to a potentially fatal but rare tachyarrhythmia known as Torsades de Pointes
      (TdP). Nonclinical assays, such as those investigating the effect on I(Kr) (the
      hERG channel current), prolongation of the action potential duration (APD) and
      the QT interval, in vivo, have been developed to predict the risk of QT interval
      prolongation and TdP in man. However, there seems to be a dissociation between
      the risk of QT interval prolongation and the torsadogenic risk. There is an
      increasing mass of evidence showing that an increase in the QT interval does not
      necessarily lead to TdP. Thus, it appears that while standard assays are very
      good, although perhaps not infallible, at predicting the risk of QT interval
      prolongation in man they do not predict the proarrhythmic risk. Recently there
      has been a plethora of publications suggesting that there are
      electrophysiological markers associated with drug-induced TdP other than hERG
      channel activity, APD and the QT interval, and these markers may be better
      predictors of TdP. In this review, three in vitro and, briefly, three in vivo
      models or methods are discussed. These proarrhythmia models use
      electrophysiological markers such as transmural dispersion of repolarization,
      action potential triangulation, instability, reverse use-dependence, and the
      incidence of early after-depolarizations to predict the risk of TdP. Most of the
      models presented have been published widely. The particular variable or set of
      variables used by each model to predict the torsadogenic propensity of a drug has
      been reported to correlate with clinical outcome. While each variable/model has
      been shown to discriminate between antiarrhythmic and nonarrhythmic drugs, these
      reports should be interpreted cautiously since none has been independently
      (externally) assessed. Each model is discussed along with its particular merits
      and shortcomings; none, as yet, having shown a predictive value that makes it
      clearly superior to the others. Proarrhythmia models, in particular in vitro
      models, challenge current perceptions of appropriate surrogates for TdP in man
      and question existing nonclinical strategies for assessing proarrhythmic risk.
      The rapid emergence of such models, compounded by the lack of a clear
      understanding of the key proarrhythmic mechanisms has resulted in a regulatory
      reluctance to embrace such models. The wider acceptance of proarrhythmia models
      is likely to occur when there is a clear understanding and agreement on the key
      proarrhythmia mechanisms. Regardless of regulatory acceptance, with further
      validation these models may still enhance pharmaceutical company decision-making
      to provide a rational basis for drug progression, particularly in areas of unmet
      medical need.

PMID- 15975833
TI  - Non-clinical evaluation of ventricular repolarization (ICH S7B): results of an
      interim survey of international pharmaceutical companies.
AB  - INTRODUCTION: The propensity of drugs to cause a potentially fatal arrhythmia,
      torsades des pointes (TdP), is a significant public health issue. The draft
      International Conference on Harmonization (ICH) S7B guidelines describe a battery
      of non-clinical studies to evaluate a drug's potential to prolong ventricular
      repolarization (VR); an accepted surrogate/risk factor for TdP. A worldwide
      survey of pharmaceutical industry practices, related to ICH S7B was conducted.
      The findings were presented at the 4th Annual Meeting of the Safety Pharmacology
      Society (SPS) meeting (Cincinnati, OH, Sept., 2004). METHODS: The survey was
      distributed by the SPS to 119 pharmaceutical companies; 29 surveys were returned.
      Survey topics included: (a) General Strategy and Testing for Risk of QT
      prolongation, (b) Study Timing and Relationship to Development, and (c)
      Application of GLPs. RESULTS: Respondents indicate that the basis for assessing
      prolongation of VR was to: remove compounds with an arrhythmic risk to humans
      (86%), to satisfy regulatory expectations (79%), or to avoid obstacles in the
      clinical development of a compound (86%). Development of a compound based on
      prolongation of VR was halted for 52% of respondents (compared to 45% in a 2003
      survey). Models used to evaluate changes in VR included: human ether a go-go
      related gene (hERG) (93%), action potential duration (APD) (68%; compared to 80%
      in the 2003 survey), and in vivo QT (100%). The distribution of assays being
      requested by regulatory agencies includes the hERG (83%), APD (28%), and in vivo
      QT (79%). In spite of uncertainty regarding the final requirements of ICH S7B,
      organizations continue to implement (36%) and validate (60%) their
      electrophysiology laboratories. SUMMARY: The survey results indicate that
      pharmaceutical companies are testing for VR prolongation of drug candidates and
      that institutions have established in-house or outsourced capabilities to
      evaluate this potential risk, even in the absence of final guidelines.

PMID- 15975835
TI  - False lumen embolization for type B dissection complicated by hemoptysis.
AB  - In this report, we describe successful treatment of a patient with hemoptysis by
      false lumen embolization of a type B aortic dissection.

PMID- 15975834
TI  - The influence of oxygen tension on the induction of nitric oxide and
      prostaglandin E2 by mechanical stress in articular cartilage.
AB  - OBJECTIVES: Articular cartilage is an avascular tissue that exists at low oxygen
      tension. Oxygen tension can influence the production of the pro-inflammatory
      mediators nitric oxide (NO) and prostaglandin E2 (PGE(2)) in cartilage, which are
      increased in osteoarthritis (OA). The synthesis of these molecules can be
      stimulated by mechanical stress, which is an important risk factor for OA. The
      objective of this study was to determine the influence of oxygen tension on the
      induction of NO and PGE(2) production in articular cartilage in response to
      mechanical stress. DESIGN: Intermittent mechanical compression (0.05MPa, 0.5Hz
      for 24h) was applied to full thickness skeletally mature porcine articular
      cartilage explants at either 20%, 5%, or 1% O(2). NO, PGE(2) and peroxynitrite
      formation were measured, and the effect of the selective nitric oxide synthase 2
      inhibitor 1400W was tested. RESULTS: Incubating articular cartilage at 5% O(2)
      significantly increased (P<0.001) baseline NO production, as compared with 1% or
      20% O(2). Peroxynitrite formation was lower at reduced oxygen tension. Mechanical
      compression significantly increased (P<0.001) NO production at 20% O(2) but not
      at 5% or 1% O(2), and significantly increased (P<0.001) PGE(2) production at 20%
      O(2) (50 fold) and 5% O(2) (4 fold) but not at 1% O(2). 1400W blocked
      mechanically induced NO production and further increased PGE(2) production at 5%
      O(2) (P<0.05). CONCLUSIONS: Oxygen tension influences the endogenous production
      of NO and PGE(2) in cartilage and can have a significant effect on the induction
      of these inflammatory mediators in response to mechanical compression.

PMID- 15975836
TI  - Intra-abdominal packing for uncontrollable haemorrhage during ruptured abdominal
      aortic aneurysm repair.
AB  - OBJECTIVE: Intra-abdominal packing is a valuable adjunct in patients with
      abdominal trauma and uncontrollable bleeding but few data exist regarding early
      and late outcome associated with this technique in patients with ruptured
      abdominal aortic aneurysm (AAA). METHODS: Interrogation of a prospective vascular
      surgical database identified 23 patients (22 men; median age 69, range 59-82,
      years) with ruptured AAA who required intra-abdominal packing for control of
      coagulopathic haemorrhage after insertion of an aortic graft between January 1982
      and December 2003. Co-morbidity, operative and outcome data were retrieved.
      RESULTS: Haemostasis was achieved and packs were removed within 48 h in 20
      patients. In those patients who had a graft inserted, the peri-operative
      mortality rate was 12 of 23 (52%) patients (vs. 172 of 455 (38%) patients who
      were not packed, NS). Three (13%) patients developed early intra-abdominal
      sepsis, which was universally fatal: graft-enteric fistula, intra-abdominal
      abscess with necrotizing fasciitis of the abdominal wound, and infected
      retroperitoneal haematoma. Two of 11 (18%) survivors developed late graft-related
      infective complications: major aortic graft infection at 6 months and symptomatic
      infected para-anastomotic aortic false aneurysm at 39 months. Early and late
      intra-abdominal infective complications were significantly more common in
      patients who were packed than in those who were not (packed: five of 23, 22% vs.
      non-packed: five of 455, 1%; p < 0.001). CONCLUSION: These data demonstrate that
      intra-abdominal packing in coagulopathic patients with ruptured AAA can achieve
      an acceptable survival rate. However, this technique may be associated with an
      increased incidence of early and late intra-abdominal infective complications.

PMID- 15975838
TI  - The immunogenicity of dendritic cell-derived exosomes.
AB  - Exosome production represents an alternate endocytic pathway for secretion.
      Multivesicular endosomes (MVE) fuse with the plasma membrane expelling internal
      vesicles or exosomes from cells. Exosome production has been recently described
      for immune cells including B cells, dendritic cells (DC), mast cells, macrophages
      and T cells. Exosomes derived from some DC populations stimulate T lymphocyte
      proliferation in vitro and have potent capacity to generate anti-tumour immune
      responses in vivo. These reported studies have involved in vitro grown mature DC
      expanded from precursors with cytokines. However, immature DC produce higher
      numbers of exosomes than mature DC and this is thought to be due to a reduction
      in endocytosis as DC mature, associated with reduced reformation of MVE and
      reduced exosome formation. This lab pioneered a method to generate immature DC in
      spleen long-term cultures (LTC). DC produced in cultures represent immature
      myeloid DC, highly endocytic but with weak capacity to stimulate T cells. LTC-DC
      produce exosomes and contain many MVE. This prompted a study of immunogenic
      potential with a view to the potential use of exosomes in vaccination and
      immunotherapy. DC produced in cultures represent immature myeloid DC, highly
      endocytic but with weak capacity to stimulate T cells. Exosomes were isolated by
      differential centrifugation from LTC-DC and shown by marker expression to arise
      by budding from the LAMP-1+ limiting endosomal membrane of MVE. These LTC-derived
      exosomes appear however to lack immunostimulatory markers like CD86, CD40, MHC-I
      and MHC-II. While LTC-DC can stimulate antigen-specific proliferation of CD4+ T
      cells, exosome preparations derived from antigen-pulsed DC were unable to
      stimulate purified naive T cells in vitro. They were however found to weakly
      activate allogeneic CD8+ T cells in vitro. Tumour antigen-pulsed LTC-DC or their
      exosomes could induce a protective response in mice against growth of a
      transplanted tumour but could not induce a response to clear an existing tumour.
      Exosomes derived from immature DC can modulate immune responses, but do not
      function in direct T cell activation in vitro. Modulation of immune responses by
      exosomes produced by immature DC may be dependent on the presence of other
      antigen presenting DC subsets in the animal. The possible function of immature DC
      and their exosomes in maintenance of tolerance and in the induction of immunity
      is discussed.

PMID- 15975840
TI  - Profiles with microscopic resolution by single-sided NMR.
AB  - A single-sided NMR sensor to produce depth profiles with microscopic spatial
      resolution is presented. It uses a novel permanent magnet geometry that generates
      a highly flat sensitive volume parallel to the scanner surface. By repositioning
      the sensitive slice across the object one-dimensional profiles of the sample
      structure can be produced with a space resolution better than 5 microm. The open
      geometry of the sensor results in a powerful testing tool to characterize
      arbitrarily sized objects in a non-destructive way.

PMID- 15975841
TI  - In vivo effect of piperine on serum and tissue glycoprotein levels in
      benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.
AB  - In recent years, considerable emphasis has been focused on identifying new cancer
      chemopreventive agents, which could be useful for the human population. Piperine
      is a pure, pungent alkaloid constituent of black and long peppers (Piper nigrum
      and Piper longum), that acts as an antioxidant and anticancer agent by its
      numerous macromolecules associated with them. In the present study, piperine was
      found to suppress benzo(a)pyrene (B(a)p) induced lung cancer in Swiss albino
      mice. In lung cancer bearing mice, altered levels of total protein and protein
      bound carbohydrate components (hexose, hexosamine and sialic acid) were observed
      in serum, lung and liver tissues. Dietary supplementation of piperine (50 mg/kg
      body weight) to B(a)p administered animals decreased the total protein and
      protein bound carbohydrate levels of lung cancer bearing animals in during
      initiation and post-initiation phases. Our data suggest that piperine may extend
      its chemopreventive effect through modulating the protein bound carbohydrate
      levels, as they are one of the indicators of tumorigenesis.

PMID- 15975842
TI  - [Analysis of target volumes for gliomas].
AB  - Gliomas are the most frequent tumors of the central nervous system of the adult.
      These intraparenchymal tumors are infiltrative and the most important criterion
      for definition of GTV and CTV is the extent of infiltration. Delineation of GTV
      and CTV for untreated and resected glioma remains a controversial and difficult
      issue because of the discrepancy between real tumor invasion and that estimated
      by CT or MRI. Is particularly helpful a joint analysis of the four different
      methods as histopathological correlations with CT and MRI, use of new modality
      imaging, pattern of relapses after treatment and interobserver studies. The
      presence of isolated tumor cells in intact brain, oedema or adjacent structures
      requires the definition of two different options for CTV: i) a geometrical option
      with GTV defined as the tumor mass revealed by the contrast-enhanced zone on CT
      or MRI and a CTV with an expanded margin of 2 or 3 cm; ii) an anatomic option
      including the entire zone of oedema or isolated tumor cell infiltration extending
      at least as far as the limits of the hyperintense zone on T2-weighted MRI.
      Inclusion of adjacent structures (such as white matter, corpus callosum,
      subarachnoid spaces) in the CTV mainly depends on the site of the tumor and size
      of the volume is generally enlarged.

PMID- 15975843
TI  - 200th anniversary of the Department of Forensic Medicine in Cracow.

PMID- 15975844
TI  - Enhanced electro-catalytic degradation of chloroorganic compounds in the presence
      of ultrasound.
AB  - The application of finely divided (black) Pd and Pd-Fe powder in the sono-electro
      catalytic reduction of chlorophenoxy herbicides (2,4-D) and chlorophenols (2,4
      DCP) in aqueous solutions allows for effective destruction of toxic chlorinated
      aromatic compounds. At 20 degrees C complete conversion of these compounds is
      observed within 10 min. On bimetallic Pd/Fe catalyst, intermediates due to the
      oxidation reaction are detected in addition to the products of dechlorination.
      The bimetallic catalyst appears to be energetically and economically superior to
      the Pd. In both cases, the reaction times were considerably shortened in
      comparison with traditional electro-catalytic processes.

PMID- 15975845
TI  - Cytotoxicity and gene induction by some essential oils in the yeast Saccharomyces
      cerevisiae.
AB  - In order to get an insight into the possible genotoxicity of essential oils (EOs)
      used in traditional pharmacological applications we tested five different oils
      extracted from the medicinal plants Origanum compactum, Coriandrum sativum,
      Artemisia herba alba, Cinnamomum camphora (Ravintsara aromatica) and Helichrysum
      italicum (Calendula officinalis) for genotoxic effects using the yeast
      Saccharomyces cerevisiae. Clear cytotoxic effects were observed in the diploid
      yeast strain D7, with the cells being more sensitive to EOs in exponential than
      in stationary growth phase. The cytotoxicity decreased in the following order:
      Origanum compactum>Coriandrum sativum>Artemisia herba alba>Cinnamomum
      camphora>Helichrysum italicum. In the same order, all EOs, except that derived
      from Helichrysum italicum, clearly induced cytoplasmic petite mutations
      indicating damage to mitochondrial DNA. However, no nuclear genetic events such
      as point mutations or mitotic intragenic or intergenic recombination were
      induced. The capacity of EOs to induce nuclear DNA damage-responsive genes was
      tested using suitable Lac-Z fusion strains for RNR3 and RAD51, which are genes
      involved in DNA metabolism and DNA repair, respectively. At equitoxic doses, all
      EOs demonstrated significant gene induction, approximately the same as that
      caused by hydrogen peroxide, but much lower than that caused by methyl
      methanesulfonate (MMS). EOs affect mitochondrial structure and function and can
      stimulate the transcriptional expression of DNA damage-responsive genes. The
      induction of mitochondrial damage by EOs appears to be closely linked to overall
      cellular cytotoxicity and appears to mask the occurrence of nuclear genetic
      events. EO-induced cytotoxicity involves oxidative stress, as is evident from the
      protection observed in the presence of ROS inhibitors such as glutathione,
      catalase or the iron-chelating agent deferoxamine.

PMID- 15975846
TI  - A Raman and infrared spectroscopic study of the uranyl silicates--weeksite,
      soddyite and haiweeite: part 2.
AB  - Raman spectroscopy has been used to study the molecular structure of a series of
      selected uranyl silicate minerals including weeksite K2[(UO2)2(Si5O13)].H2O,
      soddyite [(UO2)2SiO4.2H2O] and haiweeite Ca[(UO2)2(Si5O12(OH)2](H2O)3 with
      UO2(2+)/SiO2 molar ratio 2:1 or 2:5. Raman spectra clearly show well resolved
      bands in the 750-800 cm(-1) region and in the 950-1000 cm(-1) region assigned to
      the nu1 modes of the (UO2)2+ units and to the (SiO4)4- tetrahedra. Soddyite is
      characterized by Raman bands at 828.0, 808.6 and 801.8 cm(-1), 909.6 and 898.0
      cm(-1), and 268.2, 257.8 and 246.9 cm(-1), attributed to the nu1, nu3, and nu2
      (delta) (UO2)2+, respectively. Coincidences of the nu1 (UO2)2+ and the nu1
      (SiO4)4- is expected. Bands at 1082.2, 1071.2, 1036.3, 995.1 and 966.3 cm(-1) are
      attributed to the nu3 (SiO4)4-. Sets of Raman bands in the 200-300 cm(-1) region
      are assigned to nu2 (delta) (UO2)2+ and UO ligand vibrations. Multiple bands
      indicate the non-equivalence of the UO bonds and the lifting of the degeneracy of
      nu2 (delta) (UO2)2+ vibrations. The (SiO4)4- tetrahedral are characterized by
      bands in the 470-550 cm(-1) and in the 390-420 cm(-1) region. These bands are
      attributed to the nu4 and nu2 (SiO4)4- bending modes. The minerals show
      characteristic OH stretching bands in the 2900-3500 and 3600-3700 cm(-1).

PMID- 15975847
TI  - Simultaneous spectrophotometric determination of Fe(III), Al(III) and Cu(II) by
      partial least-squares calibration method.
AB  - A spectrophotometric method for simultaneous determination of Fe(III), Al(III)
      and Cu(II) using Alizarin Red S as a chelating agent was developed. The
      parameters controlling behavior of the system were investigated and optimum
      conditions were selected. A partial least-squares multivariate calibration method
      was used for the analysis of ternary mixtures of Fe(III), Al(III) and Cu(II) over
      the range of 450-6000, 140-4000 and 450-15000 ng ml(-1), respectively. Absorbance
      data were taken between 400 and 800 nm. Applying this method to simultaneous
      determination of these metal ions in several synthetic alloy solutions with total
      relative standard error of less than 5% validated the proposed method.

PMID- 15975848
TI  - The state of the art on platelet/red cell concentrates and MBLT-treated FFP: the
      need for an absolute standard and standardised approach.

PMID- 15975849
TI  - Current issues related to the quality of stored RBCs.
AB  - This paper reviews some current issues related to the quality of red cells
      processed and stored for transfusion. These include the storage lesion, use of
      gamma irradiation, and storage of red cells in containers of plastic made with
      non-leachable plasticizers.

PMID- 15975850
TI  - Activation of the extracellular signal-regulated kinase 1/2 pathway by AAV gene
      transfer protects retinal ganglion cells in glaucoma.
AB  - Glaucoma is the second leading cause of blindness in the world. Loss of vision in
      glaucomatous optic neuropathy is caused by the selective degeneration of retinal
      ganglion cells (RGCs). Ocular hypertension is a major risk factor in glaucoma,
      but visual field defects continue to progress in some patients despite the use of
      drugs that lower intraocular pressure. At present, there are no effective
      neuroprotective strategies for the treatment of this disease. The extracellular
      signal-regulated kinase (Erk) 1/2 pathway is an evolutionarily conserved
      mechanism used by several peptide factors to promote cell survival. Here we
      tested if selective activation of Erk1/2 protected RGCs in a rat model of
      experimental glaucoma. We used recombinant adeno-associated virus to transduce
      RGCs with genes encoding constitutively active or wild-type MEK1 (approved gene
      symbol MAP2K1), the upstream activator of Erk1/2. MEK1 gene transfer into RGCs
      markedly increased neuronal survival: 1366 +/- 70 RGCs/mm(2) (mean +/- SEM) were
      alive in the dorsal retina at 5 weeks after ocular hypertension surgery, a time
      when only 680 +/- 86 RGCs/mm(2) of these neurons remained in control eyes. We
      conclude that the Erk1/2 pathway plays a key role in the protection of RGCs from
      ocular hypertensive damage. This study identifies a novel gene therapy strategy
      in which selective activation of the Erk1/2 signaling pathway effectively slows
      cell death in glaucoma.

PMID- 15975851
TI  - Promoter dependence of plasmid-pluronics targeted alpha galactosidase A
      expression in skeletal muscle of Fabry mice.

PMID- 15975852
TI  - The presence of contractile reserve has no predictive value for the evolution of
      left ventricular function following atrio-ventricular node ablation in patients
      with permanent atrial fibrillation.
AB  - AIMS: Transcatheter ablation of the atrio-ventricular (AV) node followed by
      ventricular pacing has been shown to improve symptoms and quality of life (QOL)
      of patients with permanent atrial fibrillation (AF). In a considerable number of
      patients, cardiac function deteriorates after AV node ablation. We aimed to
      determine whether the absence of contractile reserve assessed by low dose
      dobutamine stress echocardiography (LDDSE) could identify those patients whose
      left ventricular (LV) function deteriorates after AV node ablation. METHODS: All
      25 patients studied had permanent AF for at least 12 months. LVEF was determined
      6 days and 3 months after AV node ablation by radionuclide ventriculography
      (RNV), at a paced rate of 80 beats/min. Deterioration in cardiac function was
      defined as a decrease in LVEF>5%. LDSE was performed in all patients before and
      after ablation. The presence of contractile reserve was defined as an improvement
      in regional function of >or=1 grade at low dose dobutamine in at least 4
      segments. QOL measurements were taken using Minnesota, NHBP and MPWB
      questionnaires. RESULTS: LVEF showed no improvement in the overall group (52.8+/
      11.1% vs. 51.8+/-9.8%, p=NS). QOL showed significant improvement in all
      questionnaires (Minnesota: 4.1+/-2.1 vs. 2.5+/-2, p=0.001; NHBP: 54.8+/-43.3 vs.
      34.2+/-34.3, p=0.002; MPWB: 22.2+/-4.6 vs. 19.4+/-6.2, p=0.03). There was no
      significant difference in change of LVEF between patients with and without
      contractile reserve (-0.4+/-8.7 vs. 1.6+/-11.3, p=NS). However, patients with a
      preserved LVEF at baseline showed more frequently a reduced LVEF after AV node
      ablation (62.2+/-10.4% vs. 47.5+/-7.6%, p=0.001). CONCLUSIONS: (1) The absence of
      contractile reserve does not predict deterioration of cardiac function after AV
      node ablation. (2) AV node ablation results in a significant improvement in QOL,
      which is not necessarily associated with improvement of LVEF. (3) Higher baseline
      LVEF predicts deterioration of cardiac function. These data suggest that although
      AV node ablation is an excellent way of controlling symptoms, it should be
      avoided in patients with normal LV function.

PMID- 15975853
TI  - Psychiatric comorbidity in epilepsy.
AB  - Many studies on psychiatric comorbidity in epilepsy have been performed using
      many different patient groups and diagnostic instruments. This methodological
      heterogeneity complicates comparison of the findings. In this article,
      psychiatric disorders in epilepsy are reviewed from the perspective of the DSM
      classification system. The empirical findings of axis I clinical disorders and
      axis II personality disorders are described separately. Furthermore, the
      existence and specificity of conditions such as interictal dysphoric disorder,
      interictal behavior syndrome, and psychosis of epilepsy are discussed. From the
      many studies that have been performed on this topic it can be learned that there
      is a need for well-controlled studies using representative patient groups and
      valid and standardized diagnostic instruments. So far, the majority of the
      studies have concerned axis I disorders; relatively little research has been
      performed on axis II personality disorders. More research on personality
      disorders, as well as on the relative contributions of the different (brain- and
      non-brain-related) factors to the relationship between epilepsy and psychiatric
      disorders, is recommended.

PMID- 15975855
TI  - The potential value of three-dimensional accelerometry for detection of motor
      seizures in severe epilepsy.
AB  - Seizure detection results based on the visual analysis of three-dimensional (3D)
      accelerometry (ACM) and video/EEG recordings are reported for 18 patients with
      severe epilepsy. They were monitored for 36 hours during which 897 seizures were
      detected. This was seven times higher than the number of seizures reported by
      nurses during the registration period. The results in this article demonstrate
      that 3D ACM is a valuable sensing method for seizure detection in this
      population. Four hundred twenty-eight (48%) seizures were detected by ACM. With
      3D ACM alone it was possible to detect all the seizures in 10 of the 18 patients.
      Three-dimensional ACM also was complementary to EEG in our population. ACM
      patterns during seizures were stereotypical in 95% of the motor seizures. These
      characteristic patterns are a starting point for automated seizure detection.

PMID- 15975856
TI  - Lateralizing signs during seizures in focal epilepsy.
AB  - This article reviews lateralizing semiological signs during epileptic seizures
      with respect to prediction of the side of the epileptogenic zone and, therefore,
      presurgical diagnostic value. The lateralizing significance of semiological signs
      and symptoms can frequently be concluded from knowledge of the cortical
      representation. Visual, auditory, painful, and autonomic auras, as well as ictal
      motor manifestations, e.g., version, clonic and tonic activity, unilateral
      epileptic spasms, dystonic posturing and unilateral automatisms, automatisms with
      preserved responsiveness, ictal spitting and vomiting, emotional facial
      asymmetry, unilateral eye blinking, ictal nystagmus, and akinesia, have been
      shown to have lateralizing value. Furthermore, ictal language manifestations and
      postictal features, such as Todd's palsy, postictal aphasia, postictal
      nosewiping, postictal memory dysfunction, as well as peri-ictal water drinking,
      peri-ictal headache, and ipsilateral tongue biting, are reviewed. Knowledge and
      recognition of semiological lateralizing signs during seizures is an important
      component of the presurgical evaluation of epilepsy surgery candidates and adds
      further information to video/EEG monitoring, neuroimaging, functional mapping,
      and neuropsychological evaluation.

PMID- 15975854
TI  - Prenatal corticosteroid impact on hippocampus: implications for postnatal
      outcomes.
AB  - Prenatal administration of corticosteroids is common in obstetrics to improve the
      outcome of premature deliveries. Many pregnant women receive multiple
      corticosteroid courses. Long-term follow-up studies in humans are limited, but
      those available suggest detrimental effects on the behavior of those children.
      Animal data also show adverse effects of prenatal corticosteroids mainly in the
      hippocampus, a structure sensitive to corticosteroid action. Several molecules
      involved in neuronal survival, seizure susceptibility, and behavior have been
      identified as possible targets of prenatal corticosteroid effects. These
      molecules include hippocampal glucocorticoid receptors, brain-derived
      neurotrophic factor, corticotropin-releasing hormone, and neuropeptide Y.
      Prenatal corticosteroid treatment permanently reprograms expression of these
      molecules. The future goals of research in this area include development of
      specific antagonists of corticosteroid activation pathways that would help
      differentiate between positive main effects and undesired adverse effects of
      prenatally administered corticosteroids.

PMID- 15975857
TI  - Dissemination and survival of commercial wine yeast in the vineyard: a large
      scale, three-years study.
AB  - The use of commercial wine yeast strains as starters has been extensively
      generalised over the past two decades. In this study, a large-scale sampling plan
      was devised over a period of three years in six different vineyards to evaluate
      the dynamics and survival of industrial yeast strains in the vineyard. A total of
      198 grape samples were collected at various distances from the wineries, before
      and after harvest, and yeast strains isolated after spontaneous fermentation were
      subsequently identified by molecular methods. Among 3780 yeast strains
      identified, 296 isolates had a genetic profile identical to that of commercial
      yeast strains. For a large majority (94%), these strains were recovered at very
      close proximity to the winery (10-200 m). Commercial strains were mostly found in
      the post-harvest samples, reflecting immediate dissemination. Analysis of
      population variations from year to year indicated that permanent implantation of
      commercial strains in the vineyard did not occur, but instead that these strains
      were subject to natural fluctuations of periodical appearance/disappearance like
      autochthonous strains. Our data show that dissemination of commercial yeast in
      the vineyard is restricted to short distances and limited periods of time and is
      largely favoured by the presence of water run-off.

PMID- 15975858
TI  - Carbon source dependent phosphorylation of the Gpr1 protein in the yeast Yarrowia
      lipolytica.
AB  - The Gpr1 protein of the ascomycetous yeast Yarrowia lipolytica belongs to the
      poorly characterised Gpr1/Fun34/YaaH protein family whose members have been only
      found in prokaryotes and lower eukaryotes so far. Gpr1p seems to be involved in
      acetic acid adaptation at low pH values. Here we show that Gpr1p is subjected to
      phosphorylation in dependence on the carbon source. Exhaustion of the carbon
      source resulted in a complete dephosphorylation of Gpr1p, whereas addition of a
      new carbon source caused the phosphorylation of Gpr1p. Almost all Gpr1p molecules
      became phosphorylated after addition of acetate, while other carbon sources only
      triggered the phosphorylation of about half of the Gpr1p molecules.
      Phosphorylation was found to occur at serine-37. In spite of the clear effect of
      acetate/acetic acid on the level of phosphorylation of Gpr1p, no correlation of
      phosphorylation/dephosphorylation and acetic acid hypersensitivity, caused by
      mutations within Gpr1p, was detected.

PMID- 15975859
TI  - Mutagenesis of Ala290, which modulates substrate subsite affinity at the
      catalytic interface of dimeric ThMA.
AB  - The goal of this study was to develop a maltose-producing enzyme using protein
      engineering and to clarify the relation between the substrate specificity and the
      structure of the substrate-binding site of dimeric maltogenic amylase isolated
      from Thermus (ThMA). Ala290 at the interface of ThMA dimer in the vicinity of the
      substrate-binding site was substituted with isoleucine, which may cause a
      structural change due to its bulky side chain. TLC analysis of the action pattern
      of the mutant ThMA-A290I, using maltooligosaccharides as substrates, revealed
      that ThMA-A290I used maltotetraose to produce mostly maltose, while wild-type
      ThMA produced glucose as well as maltose. The wild-type enzyme eventually
      hydrolyzed the maltose produced from maltotetraose into glucose, but the mutant
      enzyme did not. For both enzymes, the cleavage frequency of the glycosidic bond
      of maltooligosaccharides was the highest at the second bond from the reducing
      end. The mutant ThMA had a much higher Km value for maltose than the wild-type
      ThMA. The kinetic parameter, kcat/Km) of ThMA-A290I for maltose was 48 times less
      than that of wild-type ThMA, suggesting that the subsite affinity and hydrolysis
      mode of ThMA were modulated by the residue located at the interface of ThMA dimer
      near the active site. The conformational rearrangement in the catalytic interface
      probably led to the change in the substrate binding affinity of the mutant ThMA.
      Our results provide basic information for the enzymatic preparation of high
      maltose syrup.

PMID- 15975860
TI  - Over-expression, purification and characterization of the oligomerization
      dynamics of an invertebrate mitochondrial creatine kinase.
AB  - Mitochondrial creatine kinase (MtCK) plays a central role in energy homeostasis
      within cells that display high and variable rates of ATP turnover. Vertebrate
      MtCKs exist primarily as octamers but readily dissociate into constituent dimers
      under a variety of circumstances. MtCK is an ancient protein that is also found
      in invertebrates including sponges, the most primitive of all multi-cellular
      animals. We have cloned, expressed, and purified one of these invertebrate MtCKs
      from a marine polychaete worm, Chaetopterus variopedatus (CVMtCK). Size exclusion
      chromatography and dynamic light scattering (DLS) were used to characterize
      oligomeric state in comparison with that of octameric chicken sarcomeric isoform
      (SarMtCK). At protein concentrations >1 mg/ml, CVMtCK was predominantly octameric
      (>90%). When diluted to 0.1 mg/ml, CVMtCK dissociated into dimers much more
      rapidly than SarMtCK when observed under identical conditions. The rate of
      dissociation for both MtCKs increased as temperature rose from 2 to 28 degrees C,
      and in CVMtCK, fell at higher incubation temperatures. The fraction of octameric
      CVMtCK at equilibrium increased with temperature and then fell. Temperature
      transition studies showed that octamers and dimers were rapidly interconvertible
      on a similar time scale. Importantly, when CVMtCK was converted to the transition
      state analog complex (TSAC), both size exclusion chromatography and DLS showed
      that there was minimal dissociation of octamers into dimers while SarMtCK
      octamers were highly unstable as the TSAC. These results clearly show distinct
      differences in octamer stability between CVMtCK and SarMtCK, which could impact
      function under physiological circumstances. Furthermore, the large yield of
      recombinant protein and high stability of CVMtCK in the TSAC suggest that this
      protein might be a good target for crystallization efforts.

PMID- 15975861
TI  - Identifying Helicobacter pylori-associated gastritis, gastric atrophy and
      intestinal metaplasia with magnification endoscopy and adaptive index of
      haemoglobin enhancement technique.

PMID- 15975896
TI  - Sticking it to Parkinson's disease.

PMID- 15975897
TI  - Releasing the pressure.

PMID- 15975898
TI  - Endothelial progenitor cell therapy for atherosclerosis: the philosopher's stone
      for an aging population?
AB  - Much of the increased risk for atherosclerosis progression with age may be a
      result of age-related declines in the capacity of precursor cells to repair
      damage in the arterial endothelium. To estimate the impact of progenitor cell
      therapy for atherosclerosis on cardiovascular disease (CVD) mortality, life
      expectancy, and survival, as compared with the lifetime control of conventional
      risk factors, we modeled the health effects of bone marrow-derived endothelial
      progenitor cell therapy using data from the 1950 to 1996 follow-up of the
      Framingham Heart Study. To model cardiovascular disease mortality, we assumed
      that progenitor cell therapy was applied at age 30, with the effect assumed to be
      a 10-year delay in atherosclerosis progression. Age projections were constructed
      analytically using the stochastic process model for risk factor dynamics and
      mortality and microsimulation techniques. We considered three types of
      interventions: (i) keeping risk factors within selected limits to model current
      clinical recommendations; (ii) an age shift of 10 years to model the effects of
      progenitor cell therapy; and (iii) elimination of a competing risk (such as
      cancer). Our study suggests that progenitor cell therapy might increase life
      expectancy in the population as much as the complete elimination of cancer (in
      females, an additional 3.67 versus 3.37 years; in males, an additional 5.94
      versus 2.86 years, respectively).

PMID- 15975899
TI  - Na/K-ATPase tethers phospholipase C and IP3 receptor into a calcium-regulatory
      complex.
AB  - We have shown that the caveolar Na/K-ATPase transmits ouabain signals via
      multiple signalplexes. To obtain the information on the composition of such
      complexes, we separated the Na/K-ATPase from the outer medulla of rat kidney into
      two different fractions by detergent treatment and density gradient
      centrifugation. Analysis of the light fraction indicated that both PLC-gamma1 and
      IP3 receptors (isoforms 2 and 3, IP3R2 and IP3R3) were coenriched with the Na/K
      ATPase, caveolin-1 and Src. GST pulldown assays revealed that the central loop of
      the Na/K-ATPase alpha1 subunit interacts with PLC-gamma1, whereas the N-terminus
      binds IP3R2 and IP3R3, suggesting that the signaling Na/K-ATPase may tether PLC
      gamma1 and IP3 receptors together to form a Ca(2+)-regulatory complex. This
      notion is supported by the following findings. First, both PLC-gamma1 and IP3R2
      coimmunoprecipitated with the Na/K-ATPase and ouabain increased this interaction
      in a dose- and time-dependent manner in LLC-PK1 cells. Depletion of cholesterol
      abolished the effects of ouabain on this interaction. Second, ouabain induced
      phosphorylation of PLC-gamma1 at Tyr(783) and activated PLC-gamma1 in a Src
      dependent manner, resulting in increased hydrolysis of PIP2. It also stimulated
      Src-dependent tyrosine phosphorylation of the IP3R2. Finally, ouabain induced
      Ca(2+) release from the intracellular stores via the activation of IP3 receptors
      in LLC-PK1 cells. This effect required the ouabain-induced activation of PLC
      gamma1. Inhibition of Src or depletion of cholesterol also abolished the effect
      of ouabain on intracellular Ca(2+).

PMID- 15975900
TI  - Role of the regulatory domain of protein kinase D2 in phorbol ester binding,
      catalytic activity, and nucleocytoplasmic shuttling.
AB  - Protein kinase D2 (PKD2) belongs to the PKD family of serine/threonine kinases
      that is activated by phorbol esters and G protein-coupled receptors (GPCRs). Its
      C-terminal regulatory domain comprises two cysteine-rich domains (C1a/C1b)
      followed by a pleckstrin homology (PH) domain. Here, we examined the role of the
      regulatory domain in PKD2 phorbol ester binding, catalytic activity, and
      subcellular localization: The PH domain is a negative regulator of kinase
      activity. C1a/C1b, in particular C1b, is required for phorbol ester binding and
      gastrin-stimulated PKD2 activation, but it has no inhibitory effect on the
      catalytic activity. Gastrin triggers nuclear accumulation of PKD2 in living AGS-B
      cancer cells. C1a/C1b, not the PH domain, plays a complex role in the regulation
      of nucleocytoplasmic shuttling: We identified a nuclear localization sequence in
      the linker region between C1a and C1b and a nuclear export signal in the C1a
      domain. In conclusion, our results define the critical components of the PKD2
      regulatory domain controlling phorbol ester binding, catalytic activity, and
      nucleocytoplasmic shuttling and reveal marked differences to the regulatory
      properties of this domain in PKD1. These findings could explain functional
      differences between PKD isoforms and point to a functional role of PKD2 in the
      nucleus upon activation by GPCRs.

PMID- 15975902
TI  - Abl tyrosine kinase and its substrate Ena/VASP have functional interactions with
      kinesin-1.
AB  - Relatively little is known about how microtubule motors are controlled or about
      how the functions of different cytoskeletal systems are integrated. A yeast two
      hybrid screen for proteins that bind to Drosophila Enabled (Ena), an actin
      polymerization factor that is negatively regulated by Abl tyrosine kinase,
      identified kinesin heavy chain (Khc), a member of the kinesin-1 subfamily of
      microtubule motors. Coimmunoprecipitation from Drosophila cytosol confirmed a
      physical interaction between Khc and Ena. Kinesin-1 motors can carry organelles
      and other macromolecular cargoes from neuronal cell bodies toward terminals in
      fast-axonal-transport. Ena distribution in larval axons was not affected by
      mutations in the Khc gene, suggesting that Ena is not itself a fast transport
      cargo of Drosophila kinesin-1. Genetic interaction tests showed that in a
      background sensitized by reduced Khc gene dosage, a reduction in Abl gene dosage
      caused distal paralysis and axonal swellings. A concomitant reduction in ena
      dosage rescued those defects. These results suggest that Ena/VASP, when not
      inhibited by the Abl pathway, can bind Khc and reduce its transport activity in
      axons.

PMID- 15975901
TI  - HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent
      viral synapse to induce efficient HIV-1 transcytosis across epithelial cell
      monolayer.
AB  - The heparan sulfate proteoglycan agrin and adhesion molecules are key players in
      the formation of neuronal and immune synapses that evolved for efficient
      communication at the sites of cell-cell contact. Transcytosis of infectious virus
      across epithelial cells upon contact between HIV-1-infected cells and the mucosal
      pole of the epithelial cells is one mechanism for HIV-1 entry at mucosal sites.
      In contrast, transcytosis of cell-free HIV-1 is not efficient. A synapse between
      HIV-1-infected cells and the mucosal epithelial surface that resembles neuronal
      and immune synapses is visualized by electron microscopy. We have termed this the
      "viral synapse." Similarities of the viral synapse also extend to the functional
      level. HIV-1-infected cell-induced transcytosis depends on RGD-dependent
      integrins and efficient cell-free virus transcytosis is inducible upon RGD
      dependent integrin cross-linking. Agrin appears differentially expressed at the
      apical epithelial surface and acts as an HIV-1 attachment receptor. Envelope
      glycoprotein subunit gp41 binds specifically to agrin, reinforcing the
      interaction of gp41 to its epithelial receptor galactosyl ceramide.

PMID- 15975903
TI  - Alanine scanning of Arp1 delineates a putative binding site for Jnm1/dynamitin
      and Nip100/p150Glued.
AB  - Arp1p is the only actin-related protein (ARP) known to form actin-like filaments.
      Unlike actin, Arp1p functions with microtubules, as part of the dynein regulator,
      dynactin. Arp1p's dissimilar functions imply interactions with a distinct set of
      proteins. To distinguish surface features relating to Arp1p's core functions and
      to identify the footprint of protein interactions essential for dynactin
      function, we performed the first complete charge-cluster-to-alanine scanning
      mutagenesis of an ARP and compared the results with a similar study of actin. The
      Arp1p mutations revealed three nonoverlapping surfaces with distinct genetic
      properties. One of these surfaces encompassed a region unique to Arp1p that is
      crucial for Jnm1p (dynamitin/p50) and Nip100p (p150(Glued)) association as well
      as pointed-end associations. Unlike the actin mutations, none of the ARP1 alleles
      disrupt filament formation; however, one pointed-end allele delayed the elution
      of Arp1p on gel filtration, consistent with loss of additional subunits.

PMID- 15975904
TI  - A novel role for integrin-linked kinase in epithelial sheet morphogenesis.
AB  - Integrin-linked kinase (ILK) is a multidomain protein involved in cell motility
      and cell-extracellular matrix interactions. ILK is found in integrin-containing
      focal adhesions in undifferentiated primary epidermal keratinocytes. Induction of
      keratinocyte differentiation by treatment with Ca(2+) triggers formation of cell
      cell junctions, loss of focal adhesions, and ILK distribution to cell borders. We
      now show that Ca(2+) treatment of keratinocytes induces rapid (<or=1 h)
      translocation to the cell membrane of the adherens junction (AJ) proteins E
      cadherin and beta-catenin. This is followed by slower (>6 h) localization of
      tight junction (TJ) proteins. The kinetics of ILK movement toward the cell
      periphery mimics that of AJ components, suggesting that ILK plays a role in the
      early formation of cell-cell contacts. Whereas the N terminus in ILK mediates
      localization to cell borders, expression of an ILK deletion mutant incapable of
      localizing to the cell membrane (ILK 191-452) interferes with translocation of E
      cadherin/beta-catenin to cell borders, precluding Ca(2+)-induced AJ formation.
      Cells expressing ILK 191-452 also fail to form TJ and sealed cell-cell borders
      and do not form epithelial sheets. Thus, we have uncovered a novel role for ILK
      in epithelial cell-cell adhesion, independent of its well-established role in
      integrin-mediated adhesion and migration.

PMID- 15975905
TI  - A Plasmodium actin-depolymerizing factor that binds exclusively to actin
      monomers.
AB  - ADF/cofilins (AC) are essential F- and G-actin binding proteins that modulate
      microfilament turnover. The genome of Plasmodium falciparum, the parasite causing
      malaria, contains two members of the AC family. Interestingly, P. falciparum ADF1
      lacks the F-actin binding residues of the AC consensus. Reverse genetics in the
      rodent malaria model system suggest that ADF1 performs vital functions during the
      pathogenic red blood cell stages, whereas ADF2 is not present in these stages. We
      show that recombinant PfADF1 interacts with monomeric actin but does not bind to
      actin polymers. Although other AC proteins inhibit nucleotide exchange on
      monomeric actin, the Plasmodium ortholog stimulates nucleotide exchange. Thus,
      PfADF1 differs in its biochemical properties from previously known AC proteins
      and seems to promote turnover exclusively by interaction with actin monomers.
      These findings provide important insights into the low cytosolic abundance and
      unique turnover characteristics of actin polymers in parasites of the phylum
      Apicomplexa.

PMID- 15975906
TI  - Role for Gcs1p in regulation of Arl1p at trans-Golgi compartments.
AB  - ADP-ribosylation factor (ARF) and ARF-like (ARL) proteins are members of the ARF
      family, which are critical components of several different vesicular trafficking
      pathways. ARFs have little or no detectable GTPase activity without the
      assistance of a GTPase-activating protein (GAP). Here, we demonstrate that yeast
      Gcs1p exhibits GAP activity toward Arl1p and Arf1p in vitro, and Arl1p can
      interact with Gcs1p in a GTP-dependent manner. Arl1p was observed both on trans
      Golgi and in cytosol and was recruited from cytosol to membranes in a GTP
      dependent manner. In gcs1 mutant cells, the fraction of Arl1p in cytosol relative
      to trans-Golgi was less than it was in wild-type cells. Increasing Gcs1p levels
      returned the distribution toward that of wild-type cells. Both Arl1p and Gcs1p
      influenced the distribution of Imh1p, an Arl1p effector. Our data are consistent
      with the conclusion that Arl1p moves in a dynamic equilibrium between trans-Golgi
      and cytosol, and the release of Arl1p from membranes in cells requires the
      hydrolysis of bound GTP, which is accelerated by Gcs1p.

PMID- 15975907
TI  - Drosophila Mob family proteins interact with the related tricornered (Trc) and
      warts (Wts) kinases.
AB  - The function of Tricornered (Trc), the Drosophila Ndr (Nuclear Dbf2-related)
      serine/threonine protein kinase, is required for the normal morphogenesis of a
      variety of polarized outgrowths including epidermal hairs, bristles, arista
      laterals, and dendrites. In yeast the Trc homolog Cbk1 needs to bind Mob2 to
      activate the RAM pathway. In this report, we provide genetic and biochemical data
      that Drosophila Trc also interacts with and is activated by Drosophila Dmob
      proteins. In addition, Drosophila Mob proteins appear to interact with the
      related Warts/Lats kinase, which functions as a tumor suppressor in flies and
      mammals. Interestingly, the overgrowth tumor phenotype that results from
      mutations in Dmob1 (mats) was only seen in genetic mosaics and not when the
      entire animal was mutant. We conclude that unlike in yeast, in Drosophila
      individual Mob proteins interact with multiple kinases and that individual NDR
      family kinases interact with multiple Mob proteins. We further provide evidence
      that Mo25, the Drosophila homolog of the RAM pathway hym1 gene does not function
      along with Trc.

PMID- 15975908
TI  - Yeast aconitase in two locations and two metabolic pathways: seeing small amounts
      is believing.
AB  - The distribution of identical enzymatic activities between different subcellular
      compartments is a fundamental process of living cells. At present, the
      Saccharomyces cerevisiae aconitase enzyme has been detected only in mitochondria,
      where it functions in the tricarboxylic acid (TCA) cycle and is considered a
      mitochondrial matrix marker. We developed two strategies for physical and
      functional detection of aconitase in the yeast cytosol: 1) we fused the alpha
      peptide of the beta-galactosidase enzyme to aconitase and observed alpha
      complementation in the cytosol; and 2) we created an ACO1-URA3 hybrid gene, which
      allowed isolation of strains in which the hybrid protein is exclusively targeted
      to mitochondria. These strains display a specific phenotype consistent with
      glyoxylate shunt elimination. Together, our data indicate that yeast aconitase
      isoenzymes distribute between two distinct subcellular compartments and
      participate in two separate metabolic pathways; the glyoxylate shunt in the
      cytosol and the TCA cycle in mitochondria. We maintain that such dual
      distribution phenomena have a wider occurrence than recorded currently, the
      reason being that in certain cases there is a small fraction of one of the
      isoenzymes, in one of the locations, making its detection very difficult. We term
      this phenomenon of highly uneven isoenzyme distribution "eclipsed distribution."

PMID- 15975909
TI  - Inhibition of Pkhd1 impairs tubulomorphogenesis of cultured IMCD cells.
AB  - Fibrocystin/polyductin (FPC), the gene product of PKHD1, is responsible for
      autosomal recessive polycystic kidney disease (ARPKD). This disease is
      characterized by symmetrically large kidneys with ectasia of collecting ducts. In
      the kidney, FPC predominantly localizes to the apical domain of tubule cells,
      where it associates with the basal bodies/primary cilia; however, the functional
      role of this protein is still unknown. In this study, we established stable IMCD
      (mouse inner medullary collecting duct) cell lines, in which FPC was silenced by
      short hairpin RNA inhibition (shRNA). We showed that inhibition of FPC disrupted
      tubulomorphogenesis of IMCD cells grown in three-dimensional cultures. Pkhd1
      silenced cells developed abnormalities in cell-cell contact, actin cytoskeleton
      organization, cell-ECM interactions, cell proliferation, and apoptosis, which may
      be mediated by dysregulation of extracellular-regulated kinase (ERK) and focal
      adhesion kinase (FAK) signaling. These alterations in cell function in vitro may
      explain the characteristics of ARPKD phenotypes in vivo.

PMID- 15975910
TI  - GLUT1CBP(TIP2/GIPC1) interactions with GLUT1 and myosin VI: evidence supporting
      an adapter function for GLUT1CBP.
AB  - We identified a novel interaction between myosin VI and the GLUT1 transporter
      binding protein GLUT1CBP(GIPC1) and first proposed that as an adapter molecule it
      might function to couple vesicle-bound proteins to myosin VI movement. This study
      refines the model by identifying two myosin VI binding domains in the GIPC1 C
      terminus, assigning respective oligomerization and myosin VI binding functions to
      separate N- and C-terminal domains, and defining a central region in the myosin
      VI tail that binds GIPC1. Data further supporting the model demonstrate that 1)
      myosin VI and GIPC1 interactions do not require a mediating protein; 2) the
      myosin VI binding domain in GIPC1 is necessary for intracellular interactions of
      GIPC1 with myosin VI and recruitment of overexpressed myosin VI to membrane
      structures, but not for the association of GIPC1 with such structures; 3)
      GIPC1/myosin VI complexes coordinately move within cellular extensions of the
      cell in an actin-dependent and microtubule-independent manner; and 4) blocking
      either GIPC1 interactions with myosin VI or GLUT1 interactions with GIPC1
      disrupts normal GLUT1 trafficking in polarized epithelial cells, leading to a
      reduction in the level of GLUT1 in the plasma membrane and concomitant
      accumulation in internal membrane structures.

PMID- 15975911
TI  - The novel fission yeast protein Pal1p interacts with Hip1-related Sla2p/End4p and
      is involved in cellular morphogenesis.
AB  - The establishment and maintenance of characteristic cellular morphologies is a
      fundamental property of all cells. Here we describe Schizosaccharomyces pombe
      Pal1p, a protein important for maintenance of cylindrical cellular morphology.
      Pal1p is a novel membrane-associated protein that localizes to the growing tips
      of interphase cells and to the division site in cells undergoing cytokinesis in
      an F-actin- and microtubule-independent manner. Cells deleted for pal1 display
      morphological defects, characterized by the occurrence of spherical and pear
      shaped cells with an abnormal cell wall. Pal1p physically interacts and displays
      overlapping localization with the Huntingtin-interacting-protein (Hip1)-related
      protein Sla2p/End4p, which is also required for establishment of cylindrical
      cellular morphology. Sla2p is important for efficient localization of Pal1p to
      the sites of polarized growth and appears to function upstream of Pal1p.
      Interestingly, spherical pal1Delta mutants polarize to establish a pearlike
      morphology before mitosis in a manner dependent on the kelch-repeat protein Tea1p
      and the cell cycle inhibitory kinase Wee1p. Thus, overlapping mechanisms
      involving Pal1p, Tea1p, and Sla2p contribute to the establishment of cylindrical
      cellular morphology, which is important for proper spatial regulation of
      cytokinesis.

PMID- 15975912
TI  - Taxol-stabilized microtubules can position the cytokinetic furrow in mammalian
      cells.
AB  - How microtubules act to position the plane of cell division during cytokinesis is
      a topic of much debate. Recently, we showed that a subpopulation of stable
      microtubules extends past chromosomes and interacts with the cell cortex at the
      site of furrowing, suggesting that these stabilized microtubules may stimulate
      contractility. To test the hypothesis that stable microtubules can position
      furrows, we used taxol to rapidly suppress microtubule dynamics during various
      stages of mitosis in PtK1 cells. Cells with stabilized prometaphase or metaphase
      microtubule arrays were able to initiate furrowing when induced into anaphase by
      inhibition of the spindle checkpoint. In these cells, few microtubules contacted
      the cortex. Furrows formed later than usual, were often aberrant, and did not
      progress to completion. Images showed that furrowing correlated with the presence
      of one or a few stable spindle microtubule plus ends at the cortex. Actin, myosin
      II, and anillin were all concentrated in these furrows, demonstrating that
      components of the contractile ring can be localized by stable microtubules. Inner
      centromere protein (INCENP) was not found in these ingressions, confirming that
      INCENP is dispensable for furrow positioning. Taxol-stabilization of the numerous
      microtubule-cortex interactions after anaphase onset delayed furrow initiation
      but did not perturb furrow positioning. We conclude that taxol-stabilized
      microtubules can act to position the furrow and that loss of microtubule dynamics
      delays the timing of furrow onset and prevents completion. We discuss our
      findings relative to models for cleavage stimulation.

PMID- 15975913
TI  - dGRASP localization and function in the early exocytic pathway in Drosophila S2
      cells.
AB  - The de novo model for Golgi stack biogenesis predicts that membrane exiting the
      ER at transitional ER (tER) sites contains and recruits all the necessary
      molecules to form a Golgi stack, including the Golgi matrix proteins, p115,
      GM130, and GRASP65/55. These proteins leave the tER sites faster than Golgi
      transmembrane resident enzymes, suggesting that they act as a template nucleating
      the formation of the Golgi apparatus. However, the localization of the Golgi
      matrix proteins at tER sites is only shown under conditions where exit from the
      ER is blocked. Here, we show in Drosophila S2 cells, that dGRASP, the single
      Drosophila homologue of GRASP65/55, localizes both to the Golgi membranes and the
      tER sites at steady state and that the myristoylation of glycine 2 is essential
      for the localization to both compartments. Its depletion for 96 h by RNAi gave an
      effect on the architecture of the Golgi stacks in 30% of the cells, but a double
      depletion of dGRASP and dGM130 led to the quantitative conversion of Golgi stacks
      into clusters of vesicles and tubules, often featuring single cisternae. This
      disruption of Golgi architecture was not accompanied by the disorganization of
      tER sites or the inhibition of anterograde transport. This shows that, at least
      in Drosophila, the structural integrity of the Golgi stacks is not required for
      efficient transport. Overall, dGRASP exhibits a dynamic association to the
      membrane of the early exocytic pathway and is involved in Golgi stack
      architecture.

PMID- 15975914
TI  - Microglial activation induced by neurodegeneration: a proteomic analysis.
AB  - Neuroinflammation mediated by microglial activation appears to play an essential
      role in the pathogenesis of Parkinson disease; however, the mechanisms by which
      microglia are activated are not fully understood. Thus, we first evaluated the
      effects of two parkinsonian toxicants, manganese ethylene bisdithiocarbamate (Mn
      EBDC) and 1-methyl-4-phenylpyridine (MPP+), on microglial activation as well as
      associated dopaminergic (DAergic) neurotoxicity in primary cell culture systems.
      The results demonstrated that, when rat primary mesencephalic neuron-enriched or
      neuron-microglia mixed cultures were treated with Mn-EBDC at 2-8 microm or MPP+
      at 0.25-5 microm, respectively, for 7 days, both toxicants were capable of
      inducing DAergic neurodegeneration as well as activating microglia via a
      mechanism secondary to DAergic neurodegeneration. Furthermore activated microglia
      subsequently enhanced DAergic neurotoxicity induced by Mn-EBDC or MPP+. Detailed
      scrutiny of neuron-microglia interactions identified a fraction of the
      conditioned media derived from a DAergic cell line treated with Mn-EBDC or MPP+
      that potently activated microglia. To further define potential mediators leading
      to microglial activation secondary to neurodegeneration, we utilized a
      quantitative proteomic technique termed SILAC (for stable isotope labeling by
      amino acids in cell culture) to compare the protein profiles of MPP+-treated
      cellular fraction that mediated microglial activation as compared with controls.
      The search revealed numerous novel proteins that are potentially important in
      neurodegeneration-mediated microglial activation, a process believed to be
      critical in Parkinson disease progression.

PMID- 15975915
TI  - Proteomic analysis of cellular response to osmotic stress in thick ascending limb
      of Henle's loop (TALH) cells.
AB  - Epithelial cells of the thick ascending limb of Henle's loop (TALH cells) play a
      major role in the urinary concentrating mechanism. They are normally exposed to
      variable and often very high osmotic stress, which is particularly due to high
      sodium and chloride reabsorption and very low water permeability of the luminal
      membrane. It is already established that elevation of the activity of aldose
      reductase and hence an increase in intracellular sorbitol are indispensable for
      the osmotic adaptation and stability of the TALH cells. To identify new molecular
      factors potentially associated with the osmotic stress-resistant phenotype in
      kidney cells, TALH cells exhibiting low or high levels of resistance to osmotic
      stress were characterized using proteomic tools. Two-dimensional gel analysis
      showed a total number of 40 proteins that were differentially expressed in TALH
      cells under osmotic stress. Twenty-five proteins were overexpressed, whereas 15
      proteins showed a down-regulation. Besides the sorbitol pathway enzyme aldose
      reductase, whose expression was 15 times increased, many other metabolic enzymes
      like glutathione S-transferase, malate dehydrogenase, lactate dehydrogenase,
      alpha enolase, glyceraldehyde-3-phosphate dehydrogenase, and triose-phosphate
      isomerase were up-regulated. Among the cytoskeleton proteins and cytoskeleton
      associated proteins vimentin, cytokeratin, tropomyosin 4, and annexins I, II, and
      V were up-regulated, whereas tubulin and tropomyosins 1, 2, and 3 were down
      regulated. The heat shock proteins alpha-crystallin chain B, HSP70, and HSP90
      were found to be overexpressed. In contrast to the results in oxidative stress
      the endoplasmic reticulum stress proteins like glucose-regulated proteins (GRP78,
      GRP94, and GRP96), calreticulin, and protein-disulfide isomerase were down
      regulated under hypertonic stress.

PMID- 15975916
TI  - Depolarization of neural cells induces transcription of the Down syndrome
      critical region 1 isoform 4 via a calcineurin/nuclear factor of activated T cells
      dependent pathway.
AB  - In this study we showed that the transcriptional regulation of Down syndrome
      critical region isoform 4 (DSCR1.4) is mediated by the calcineurin/nuclear factor
      of activated T cells (NFAT) pathway in neural cells. Stimuli that elicit an
      increase in the intracellular concentrations of calcium, such as membrane
      depolarization, induced de novo transcription of DSCR1.4, with mRNA expression
      peaking after 4 h and then declining. Action via the physiologically relevant L
      type calcium channel was confirmed by blockade with nifedipine and verapamil.
      This calcium-dependent transcription of DSCR1.4 was inhibited by the calcineurin
      inhibitors cyclosporin A and FK506. Deletional analysis showed that the calcium-
      and calcineurin-dependent activation is mediated by the promoter region between
      nucleotides -350 and -166, a region that contains putative NFAT-binding motifs.
      Exogenous NFATc2 potently augmented the DSCR1.4 promoter transcriptional
      activity, and the involvement of endogenous NFAT signaling pathway in DSCR1.4
      transcription was confirmed by the suppression of depolarization-inducible
      promoter activity with the NFAT inhibitor peptide VIVIT. Exogenous overexpression
      of DSCR1 protein (calcipressin 1) resulted in the inhibition of the transcription
      of DSCR1.4 and NFAT-dependent signaling. These findings suggest that calcineurin
      dependent induction of DSCR1.4 product may represent an important auto-regulatory
      mechanism for the homeostatic control of NFAT signaling in neural cells.

PMID- 15975917
TI  - Location of the coenzyme binding site in the porcine mitochondrial NADP-dependent
      isocitrate dehydrogenase.
AB  - The structure of crystalline porcine mitochondrial NADP-dependent isocitrate
      dehydrogenase (IDH) has been determined in complex with Mn2+-isocitrate. Based on
      structural alignment between this porcine enzyme and seven determined crystal
      structures of complexes of NADP with bacterial IDHs, Arg83, Thr311, and Asn328
      were chosen as targets for site-directed mutagenesis of porcine IDH. The circular
      dichroism spectra of purified wild-type and mutant enzymes are similar. The
      mutant enzymes exhibit little change in Km for isocitrate or Mn2+, showing that
      these residues are not involved in substrate binding. In contrast, the Arg83
      mutants, Asn328 mutants, and T311A exhibit 3-20-fold increase in the Km(NADP). We
      propose that Arg83 enhances NADP affinity by hydrogen bonding with the 3'-OH of
      the nicotinamide ribose, whereas Asn328 hydrogen bonds with N1 of adenine. The pH
      dependence of Vmax for Arg83 and Asn328 mutants is similar to that of wild-type
      enzyme, but for all the Thr311 mutants, pK(es) is increased from 5.2 in the wild
      type to approximately 6.0. We have previously attributed the pH dependence of
      Vmax to the deprotonation of the metal-bound hydroxyl of isocitrate in the enzyme
      substrate complex, prior to the transfer of a hydride from isocitrate to NADP's
      nicotinamide moiety. Thr311 interacts with the nicotinamide ribose and is the
      closest of the target amino acids to the nicotinamide ring. Distortion of the
      nicotinamide by Thr311 mutation will likely be transmitted to Mn2+-isocitrate
      resulting in an altered pK(es). Because porcine and human mitochondrial NADP-IDH
      have 95% sequence identity, these results should be applicable to the human
      enzyme.

PMID- 15975918
TI  - Stabilization of non-productive conformations underpins rapid electron transfer
      to electron-transferring flavoprotein.
AB  - Crystal structures of protein complexes with electron-transferring flavoprotein
      (ETF) have revealed a dual protein-protein interface with one region serving as
      anchor while the ETF FAD domain samples available space within the complex. We
      show that mutation of the conserved Glu-165beta in human ETF leads to drastically
      modulated rates of interprotein electron transfer with both medium chain acyl-CoA
      dehydrogenase and dimethylglycine dehydrogenase. The crystal structure of free
      E165betaA ETF is essentially identical to that of wild-type ETF, but the crystal
      structure of the E165betaA ETF.medium chain acyl-CoA dehydrogenase complex
      reveals clear electron density for the FAD domain in a position optimal for fast
      interprotein electron transfer. Based on our observations, we present a dynamic
      multistate model for conformational sampling that for the wild-type ETF. medium
      chain acyl-CoA dehydrogenase complex involves random motion between three
      distinct positions for the ETF FAD domain. ETF Glu-165beta plays a key role in
      stabilizing positions incompatible with fast interprotein electron transfer, thus
      ensuring high rates of complex dissociation.

PMID- 15975919
TI  - Microtubule regulation of N-methyl-D-aspartate receptor channels in neurons.
AB  - N-Methyl-D-aspartate (NMDA) receptors (NMDARs), which play a key role in synaptic
      plasticity, are dynamically regulated by many signaling molecules and scaffolding
      proteins. Although actin cytoskeleton has been implicated in regulating NMDAR
      stability in synaptic membrane, the role of microtubules in regulating NMDAR
      trafficking and function is largely unclear. Here we show that microtubule
      depolymerizing agents inhibited NMDA receptor-mediated ionic and synaptic
      currents in cortical pyramidal neurons. This effect was Ca(2+)-independent,
      required GTP, and was more prominent in the presence of high NMDA concentrations.
      The NR2B subunit-containing NMDA receptor was the primary target of microtubules.
      The effect of microtubule depolymerizers on NMDAR currents was blocked by
      cellular knockdown of the kinesin motor protein KIF17, which transports NR2B
      containing vesicles along microtubule in neuronal dendrites. Neuromodulators that
      can stabilize microtubules, such as brain-derived neurotrophic factor,
      significantly attenuated the microtubule depolymerizer-induced reduction of NMDAR
      currents. Moreover, immunocytochemical studies show that microtubule
      depolymerizers decreased the number of surface NR2B subunits on dendrites, which
      was prevented by the microtubule stabilizer. Taken together, these results
      suggest that interfering with microtubule assembly suppresses NMDAR function
      through a mechanism dependent on kinesin-based dendritic transport of NMDA
      receptors.

PMID- 15975920
TI  - Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic
      protein co-receptor.
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta (TGF-beta) superfamily of ligands, which regulate many mammalian physiologic
      and pathophysiologic processes. BMPs exert their effects through type I and type
      II serine/threonine kinase receptors and the Smad intracellular signaling
      pathway. Recently, the glycosylphosphatidylinositol (GPI)-anchored protein DRAGON
      was identified as a co-receptor for BMP signaling. Here, we investigate whether a
      homologue of DRAGON, repulsive guidance molecule (RGMa), is similarly involved in
      the BMP signaling pathway. We show that RGMa enhances BMP, but not TGF-beta,
      signals in a ligand-dependent manner in cell culture. The soluble extracellular
      domain of RGMa fused to human Fc (RGMa.Fc) forms a complex with BMP type I
      receptors and binds directly and selectively to radiolabeled BMP-2 and BMP-4.
      RGMa mediates BMP signaling through the classical BMP signaling pathway involving
      Smad1, 5, and 8, and it up-regulates endogenous inhibitor of differentiation
      (Id1) protein, an important downstream target of BMP signals. Finally, we
      demonstrate that BMP signaling occurs in neurons that express RGMa in vivo. These
      data are consistent with a role for RGMa as a BMP co-receptor.

PMID- 15975921
TI  - Bcl-2 positively regulates Sox9-dependent chondrocyte gene expression by
      suppressing the MEK-ERK1/2 signaling pathway.
AB  - Bcl-2 is an anti-apoptotic protein that has recently been shown to regulate other
      cellular functions. We previously reported that Bcl-2 regulates chondrocyte
      matrix gene expression, independent of its anti-apoptotic function. Here, we
      further investigate this novel function of Bcl-2 and examine three intracellular
      signaling pathways likely to be associated with this function. The present study
      demonstrates that the activity of Sox9, a master transcription factor that
      regulates the gene expression of chondrocyte matrix proteins, is suppressed by
      Bcl-2 small interference RNA in the presence of caspase inhibitors. This effect
      was attenuated by prior exposure of chondrocytes to an adenoviral vector
      expressing sense Bcl-2. In addition, the down-regulation of Bcl-2, Sox9, and
      chondrocyte-specific gene expression by serum withdrawal in primary chondrocytes
      was reversed by expressing Bcl-2. Inhibition of the protein kinase C alpha and
      NFkappaB pathways had no effect on the maintenance of Sox9-dependent gene
      expression by Bcl-2. In contrast, whereas the MEK-ERK1/2 pathway negatively
      regulated the differentiated phenotype in wild type chondrocytes, inhibition of
      this pathway reversed the loss of differentiation markers and fibroblastic
      phenotype in Bcl-2-deficient chondrocytes. In conclusion, the present study
      identifies a specific signaling pathway, namely, MEK-ERK1/2, that is downstream
      of Bcl-2 in the regulation of Sox9-dependent chondrocyte gene expression and
      phenotype.

PMID- 15975922
TI  - Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear
      lamina.
AB  - Replication of human cytomegalovirus is limited at the level of nucleocytoplasmic
      transport of viral capsids, a process that requires the disassembly of the
      nuclear lamina. Deletion of the protein kinase gene UL97 from the viral genome
      showed that the activity of pUL97 plays an important role for viral capsid
      egress. Here, we report that p32, a novel cellular interactor of the viral kinase
      pUL97, promotes the accumulation of pUL97 at the nuclear membrane by recruiting
      the p32-pUL97 complex to the lamin B receptor. Transfection of active pUL97, but
      not a catalytically inactive mutant, induced a redistribution of lamina
      components as demonstrated for recombinant lamin B receptor-green fluorescent
      protein and endogenous lamins A and C. Consistent with this, p32 itself and
      lamins were phosphorylated by pUL97. Importantly, overexpression of p32 in human
      cytomegalovirus-infected cells resulted in increased efficiency of viral
      replication and release of viral particles. Thus, it is highly suggestive that
      the cellular protein p32 recruits pUL97 to induce a dissolution of the nuclear
      lamina thereby facilitating the nuclear export of viral capsids.

PMID- 15975923
TI  - Human T-lymphotropic virus, type 1, tax protein triggers microtubule
      reorientation in the virological synapse.
AB  - We showed recently that the human T-lymphotropic virus, type 1 (HTLV-1), spreads
      directly from cell to cell via a virological synapse. The HTLV-1 virological
      synapse resembles the immunological synapse; each is a specialized contact
      between a lymphocyte and another cell that contains organized protein
      microdomains, and each involves repolarization of the T-cell microtubule
      cytoskeleton. However, formation of the virological synapse is not triggered by T
      cell receptor-mediated antigen recognition. On the basis of our previous data, we
      postulated that formation of the viral synapse was triggered by a conjunction of
      two signals, one from HTLV-1 infection of the T-cell and one from cell-cell
      contact. We have recently identified ICAM-1 engagement as a cell-contact signal
      that causes the microtubule polarization associated with the virological synapse.
      Here we used confocal microscopy of T-lymphocytes naturally infected with HTLV-1
      or transfected with individual HTLV-1 genes to investigate the role of the viral
      transcriptional transactivator protein Tax. Polarization of the microtubules was
      induced by cell-cell contact or by cross-linking T-cell surface molecules with
      monoclonal antibodies adsorbed to latex beads. We show that Tax, which is mainly
      found in the nucleus, is also present at two specific extranuclear sites as
      follows: around the microtubule organizing center in association with the cis
      Golgi and in the cell-cell contact region. We show that expression of Tax
      provides an intracellular signal that synergizes with ICAM-1 engagement to cause
      the T-cell microtubule polarization observed at the virological synapse.

PMID- 15975924
TI  - Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through
      ubiquitin-proteasome pathway.
AB  - Differentiation of naive CD4 T cells into Th2 cells requires protein expression
      of GATA3. Interleukin-4 induces STAT6 activation and subsequent GATA3
      transcription. Little is known, however, on how T cell receptor-mediated
      signaling regulates GATA3 and Th2 cell differentiation. Here we demonstrated that
      T cell receptor-mediated activation of the Ras-ERK MAPK cascade stabilizes GATA3
      protein in developing Th2 cells through the inhibition of the ubiquitin
      proteasome pathway. Mdm2 was associated with GATA3 and induced ubiquitination on
      GATA3, suggesting its role as a ubiquitin-protein isopeptide ligase for GATA3
      ubiquitination. Thus, the Ras-ERK MAPK cascade controls GATA3 protein stability
      by a post-transcriptional mechanism and facilitates GATA3-mediated chromatin
      remodeling at Th2 cytokine gene loci leading to successful Th2 cell
      differentiation.

PMID- 15975925
TI  - Increasing mitochondrial substrate-level phosphorylation can rescue respiratory
      growth of an ATP synthase-deficient yeast.
AB  - In a previous study we have identified Fmc1p, a mitochondrial protein involved in
      the assembly/stability of the yeast F0F1-ATP synthase at elevated temperatures.
      The deltafmc1 mutant was shown to exhibit a severe phenotype of very slow growth
      on respiratory substrates at 37 degrees C. We have isolated ODC1 as a multicopy
      suppressor of the fmc1 deletion restoring a good respiratory growth. Odc1p
      expression level was estimated to be at least 10 times higher in mitochondria
      isolated from the deltafmc1/ODC1 transformant as compared with wild type
      mitochondria. Interestingly, ODC1 encodes an oxodicarboxylate carrier, which
      transports alpha-ketoglutarate and alpha-ketoadipate or any other transported
      tricarboxylic acid cycle intermediate in a counter-exchange through the inner
      mitochondrial membrane. We show that the suppression of the respiratory-growth
      deficient fmc1 by the overexpressed Odc1p was not due to a restored stable ATP
      synthase. Instead, the rescuing mechanism involves an increase in the flux of
      tricarboxylic acid cycle intermediate from the cytosol into the mitochondria,
      leading to an increase in the alpha-ketoglutarate oxidative decarboxylation,
      resulting in an increase in mitochondrial substrate-level-dependent ATP
      synthesis. This mechanism of metabolic bypass of a defective ATP synthase
      unravels the physiological importance of intramitochondrial substrate-level
      phosphorylations. This unexpected result might be of interest for the development
      of therapeutic solutions in pathologies associated with defects in the oxidative
      phosphorylation system.

PMID- 15975926
TI  - Roscovitine targets, protein kinases and pyridoxal kinase.
AB  - (R)-Roscovitine (CYC202) is often referred to as a "selective inhibitor of cyclin
      dependent kinases." Besides its use as a biological tool in cell cycle, neuronal
      functions, and apoptosis studies, it is currently evaluated as a potential drug
      to treat cancers, neurodegenerative diseases, viral infections, and
      glomerulonephritis. We have investigated the selectivity of (R)-roscovitine using
      three different methods: 1) testing on a wide panel of purified kinases that,
      along with previously published data, now reaches 151 kinases; 2) identifying
      roscovitine-binding proteins from various tissue and cell types following their
      affinity chromatography purification on immobilized roscovitine; 3) investigating
      the effects of roscovitine on cells deprived of one of its targets, CDK2.
      Altogether, the results show that (R)-roscovitine is rather selective for CDKs,
      in fact most kinases are not affected. However, it binds an unexpected, non
      protein kinase target, pyridoxal kinase, the enzyme responsible for
      phosphorylation and activation of vitamin B6. These results could help in
      interpreting the cellular actions of (R)-roscovitine but also in guiding the
      synthesis of more selective roscovitine analogs.

PMID- 15975927
TI  - CCR5 N-terminal region plays a critical role in HIV-1 inhibition by Toxoplasma
      gondii-derived cyclophilin-18.
AB  - Molecular mimicry of chemokine ligands has been described for several pathogens.
      Toxoplasma gondii produces a protein, cyclophilin-18 (C-18), which binds to the
      human immunodeficiency virus (HIV) co-receptor CCR5 and inhibits fusion and
      infection of T cells and macrophages by R5 viruses but not by X4 viruses. We
      recently identified structural determinants of C-18 required for anti-HIV
      activity (Yarovinsky, F., Andersen, J. F., King, L. R., Caspar, P., Aliberti, J.,
      Golding, H., and Sher, A. (2004) J. Biol. Chem. 279, 53635-53642). Here we have
      elucidated the fine specificity of CCR5 residues involved in binding and HIV
      inhibitory potential of C-18. To delineate the regions of CCR5 involved in C-18
      binding, we analyzed C-18 inhibition of cells expressing CXCR4/CCR5 chimeric
      receptors and CCR5 with a truncated N terminus (Delta2-19). These experiments
      identified a critical role for the N terminus of CCR5 in C-18 binding and anti
      HIV activity. Studies with a large panel of CCR5 N-terminal peptides, including
      Tyr-sulfated analogues, truncated peptides, and alanine-scanning mutants,
      suggested that each of the 12-17 amino acids in the N terminus of CCR5 are
      essential for C-18 binding and inhibitory activity. Tyr sulfation did not improve
      C-18 reactivity. This finding is of interest because the same CCR5 N-terminal
      region was shown previously to play a key role in binding of HIV-1 envelope
      glycoproteins. The elucidation of the functional C-18-binding mechanism may help
      in the rational design of novel antiviral agents against HIV.

PMID- 15975928
TI  - A helical hairpin region of soluble annexin B12 refolds and forms a continuous
      transmembrane helix at mildly acidic pH.
AB  - Annexins are soluble proteins that are best known for their ability to undergo
      reversible Ca(2+)-dependent binding to the surface of phospholipid bilayers.
      Recent studies, however, have shown that annexins also reversibly bind to
      membranes in a Ca(2+)-independent manner at mildly acidic pH. We investigated the
      structural changes that occur upon pH-dependent membrane binding by performing a
      nitroxide scan on the helical hairpin encompassing helices A and B in the fourth
      repeat of annexin B12. Residues 251-273 of annexin B12 were replaced, one at a
      time, with cysteine and then labeled with a nitroxide spin label. Electron
      paramagnetic resonance (EPR) mobility and accessibility analyses of soluble
      annexin B12 derivatives were in excellent agreement with the known crystal
      structure of annexin B12. However, EPR studies of annexin B12 derivatives bound
      to membranes at pH 4.0 indicated major structural changes in the scanned region.
      The helix-loop-helix structure present in the soluble protein was converted into
      a continuous transmembrane alpha-helix that was exposed to the hydrophobic core
      of the bilayer on one side and exposed to an aqueous pore on the other side. Asp
      264 was on the hydrophobic membrane-exposed face of the amphipathic transmembrane
      helix, thereby suggesting that protonation of its carboxylate group stabilized
      the transmembrane form. Inspection of the amino acid sequence of annexin B12
      revealed several other helical hairpin regions that might refold and form
      continuous amphipathic transmembrane helices in response to protonation of Asp or
      Glu switch residues on or near the hydrophobic face of the helix.

PMID- 15975929
TI  - A cell-permeable, activity-based probe for protein and lipid kinases.
AB  - Protein and lipid kinases are two important classes of biomedically relevant
      enzymes. The expression and activity of many kinases are known to be dysregulated
      in a variety of diseases, and proteomic tools that can assess the presence and
      activity of these enzymes are likely to be useful for their evaluation. Because
      many of the mechanisms by which protein kinases can become unregulated involve
      post-translational modifications or changes in protein localization, they can
      only be detected by examining protein activity, sometimes within the context of
      the living cell. Wortmannin is a steroid-derived fungal metabolite that
      covalently inhibits both protein and lipid kinases. Here we describe the
      synthesis of three wortmannin derivatives, biotin-wortmannin, BODIPY-wortmannin,
      and tetramethylrhodamine-wortmannin. We demonstrate that these reagents exhibit
      reactivity similarly as wortmannin and react with members of the
      phosphatidylinositol 3-kinase and PI3-kinase related kinase families in cellular
      lysates. Moreover, in some cases these reagents can differentiate between the
      active and inactive forms of the enzyme, indicating that they are activity-based
      probes. The reagents also exhibit complementary properties. The biotin-wortmannin
      reagent is effective in the isolation of labeled proteins; all three can be used
      for protein labeling, and BODIPY-wortmannin is cell-permeable and can be used to
      label proteins within cells.

PMID- 15975930
TI  - The proximal carboxyl-terminal domains of ADAMTS13 determine substrate
      specificity and are all required for cleavage of von Willebrand factor.
AB  - ADAMTS13 limits platelet-rich thrombosis by cleaving von Willebrand factor at the
      Tyr(1605)-Met(1606) bond. Previous studies showed that ADAMTS13 truncated after
      spacer domain remains proteolytically active or hyperactive. However, the
      relative contribution of each domain within the proximal carboxyl terminus of
      ADAMTS13 in substrate recognition and specificity is not known. We showed that a
      metalloprotease domain alone was unable to cleave the Tyr-Met bond of glutathione
      S-transferase (GST)-VWF73-H substrate in 3 h, but it did cleave the substrate at
      a site other than the Tyr-Met bond after 16-24 h of incubation. Remarkably, the
      addition of even one or several proximal carboxyl-terminal domains of ADAMTS13
      restored substrate specificity. Full proteolytic activity, however, was not
      achieved until all of the proximal carboxyl-terminal domains were added. The
      addition of TSP1 2-8 repeats and two CUB domains did not further increase
      proteolytic activity. Furthermore, ADAMTS13 truncated after the spacer domain
      with or without metalloprotease domain bound GST-VWF73-H with a K(d) of
      approximately 7.0 or 13 nm, comparable with full-length ADAMTS13 (K(d) = 4.6 nm).
      Metalloprotease domain did not bind GST-VWF73-H detectably, but the disintegrin
      domain, first TSP1 repeat, Cys-rich domain, and spacer domain bound GST-VWF73-H
      with K(d) values of 489, 136, 121, and 108 nm, respectively. These proximal
      carboxyl-terminal domains dose-dependently inhibited cleavage of fluorescent
      resonance energy transfer (FRETS)-VWF73 by full-length ADAMTS13 and ADAMTS13
      truncated after the spacer domain. These data demonstrated that the proximal
      carboxyl-terminal domains of ADAMTS13 determine substrate specificity and are all
      required for recognition and cleavage of von Willebrand factor between amino acid
      residues Asp(1595) and Arg(1668).

PMID- 15975931
TI  - Protein kinase A-dependent phosphorylation of Lutheran/basal cell adhesion
      molecule glycoprotein regulates cell adhesion to laminin alpha5.
AB  - Lutheran (Lu) blood group and basal cell adhesion molecule (B-CAM) antigens
      reside on two glycoprotein (gp) isoforms Lu and Lu(v13) that belong to the Ig
      superfamily and differ only by the size of their cytoplasmic tail. Lu/B-CAM gps
      have been recognized as laminin alpha5 receptors on red blood cells and
      epithelial cells in multiple tissues. It has been shown that sickle red cells
      exhibit enhanced adhesion to laminin alpha5 when intracellular cAMP is up
      regulated by physiological stimuli such as epinephrine and that this signaling
      pathway is protein kinase A- and Lu/B-CAM-dependent. In this study, we analyzed
      the relationship between the phosphorylation status of Lu/B-CAM gps and their
      adhesion function to laminin alpha5. We showed that Lu isoform was phosphorylated
      in sickle red cells as well as in erythroleukemic K562 and epithelial Madin-Darby
      canine kidney cells and that this phosphorylation is enhanced by different
      stimuli of the PKA pathway. Lu gp is phosphorylated by glycogen synthase kinase 3
      beta, casein kinase II, and PKA at serines 596, 598, and 621, respectively.
      Alanine substitutions of serines 596 and 598 abolished phosphorylation by
      glycogen synthase kinase 3 beta and casein kinase II, respectively, but had no
      effect on adhesion of K562 cells to laminin under flow conditions. Conversely,
      mutation of serine 621 prevented phosphorylation by PKA and dramatically reduced
      cell adhesion. Furthermore, stimulation of K562 cells by epinephrine increased Lu
      gp phosphorylation by PKA and enhanced adhesion to laminin. It is postulated that
      modulation of the phosphorylation state of Lu gp might be a critical factor for
      the sickle red cells adhesiveness to laminin alpha5 in sickle cell disease.

PMID- 15975932
TI  - Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic
      reticulum stress-induced apoptosis.
AB  - Alterations in cellular homeostasis that affect protein folding in the
      endoplasmic reticulum (ER) trigger a signaling pathway known as the unfolded
      protein response (UPR). The initially cytoprotective UPR will trigger an
      apoptotic cascade if the cellular insult is not corrected; however, the proteins
      required to initiate this cell death pathway are poorly understood. In this
      study, we show that UPR gene expression is induced in cells treated with ER
      stress agents in the presence or absence of murine caspase-12 or human caspase-4
      expression and in cells that overexpress Bcl-x(L) or a dominant negative caspase
      9. We further demonstrate that ER stress-induced apoptosis is a caspase-dependent
      process that does not require the expression of caspase-12 or caspase-4 but can
      be inhibited by overexpression of Bcl-x(L) or a dominant negative caspase-9.
      Additionally, treatment of human and murine cells with ER stress agents led to
      the cleavage of the caspase-4 fluorogenic substrate, LEVD-7-amino-4
      trifluoromethylcoumarin, in the presence or absence of caspase-12 or caspase-4
      expression, whereas Bcl-x(L) or a dominant negative caspase-9 overexpression
      inhibited LEVD-7-amino-4-trifluoromethylcoumarin cleavage. These data suggest
      that caspase-12 and caspase-4 are not required for the induction of ER stress
      induced apoptosis and that caspase-4-like activity is not always associated with
      an initiating event.

PMID- 15975933
TI  - Cleavage of p21/WAF1/CIP1 by proteinase 3 modulates differentiation of a
      monocytic cell line. Molecular analysis of the cleavage site.
AB  - Proteinase 3 (PR3), also called myeloblastin, is involved in the control of
      myeloid cell growth, but the underlying molecular mechanisms have not been
      elucidated. In U937/PR3, stably transfected with PRCRSV/PR3 to overexpress PR3,
      PMA-induced p21 expression was significantly decreased as compared with control
      U937, and this phenomenon was reversed in the presence of the serine proteinase
      inhibitor, pefabloc. Conversely, when PR3 was inactivated by small interfering
      RNA, p21 protein was increased, and PMA-induced monocytic differentiation was
      potentiated. Mass spectrometry analysis identified Ala45 as the primary cleavage
      site on p21, and the recombinant mutated p21A45R, generated by site-directed
      mutagenesis and expressed in Escherichia coli, was resistant to in vitro PR3
      cleavage. The U937 cells were then stably transfected with either PRCRSV/p21 or
      PRCRSV/p21A45R, to ectopically express wild type p21 or PR3-resistant p21,
      respectively. In U937/p21A45R treated with PS-341, a selective proteasome
      inhibitor, a significant decrease in the S phase and a blockade in the G0-G1
      phase of cell cycle were observed when compared with U937/p21 or control U937.
      This suggested that both PR3 and the proteasome are efficiently involved in the
      proteolytic regulation of p21 expression in myeloid cells. Moreover, PMA-induced
      p21 expression was more pronounced in U937/p21A45R compared with U937/p21 and was
      concomitant with the morphological features of early differentiation. Our data
      demonstrated that p21 is one specific target of PR3 and that PR3-mediated p21
      cleavage prevents monocytic differentiation.

PMID- 15975934
TI  - Development of a research registry for primary care community-based research.

PMID- 15975935
TI  - Lateral inhibition in proneural clusters: cis-regulatory logic and default
      repression by Suppressor of Hairless.
AB  - Lateral inhibition, wherein a single cell signals to its neighbors to prevent
      them from adopting its own fate, is the best-known setting for cell-cell
      communication via the Notch (N) pathway. During peripheral neurogenesis in
      Drosophila, sensory organ precursor (SOP) cells arise within proneural clusters
      (PNCs), small groups of cells endowed with SOP fate potential by their expression
      of proneural transcriptional activators. SOPs use N signaling to activate in
      neighboring PNC cells the expression of multiple genes that inhibit the SOP fate.
      These genes respond transcriptionally to direct regulation by both the proneural
      proteins and the N pathway transcription factor Suppressor of Hairless [Su(H)],
      and their activation is generally highly asymmetric; i.e. only in the inhibited
      (non-SOP) cells of the PNC, and not in SOPs. We show that the substantially
      higher proneural protein levels in the SOP put this cell at risk of
      inappropriately activating the SOP-inhibitory genes, even without input from N
      activated Su(H). We demonstrate that this is prevented by direct ;default'
      repression of these genes by Su(H), acting through the same binding sites it uses
      for activation in non-SOPs. We show that de-repression of even a single N pathway
      target gene in the SOP can extinguish the SOP cell fate. Finally, we define
      crucial roles for the adaptor protein Hairless and the co-repressors Groucho and
      CtBP in conferring repressive activity on Su(H) in the SOP. Our work elucidates
      the regulatory logic by which N signaling and the proneural proteins cooperate to
      create the neural precursor/epidermal cell fate distinction during lateral
      inhibition.

PMID- 15975936
TI  - C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant
      oocytes.
AB  - The major sperm protein (MSP) is the central cytoskeletal element required for
      actin-independent motility of nematode spermatozoa. MSP has a dual role in
      Caenorhabditis elegans reproduction, functioning as a hormone for both oocyte
      meiotic maturation and ovarian muscle contraction. The identification of the
      signaling function of MSP raised the question, how do spermatozoa, which are
      devoid of ribosomes, ER and Golgi, release a cytoplasmic protein lacking a signal
      sequence? Here, we provide evidence that MSP export occurs by the budding of
      novel vesicles that have both inner and outer membranes with MSP sandwiched in
      between. MSP vesicles are apparently labile structures that generate long-range
      MSP gradients for signaling at the oocyte cell surface. Both spermatozoa and non
      motile spermatids bud MSP vesicles, but their stability and signaling properties
      differ. Budding protrusions from the cell body contain MSP, but not the MSD
      proteins, which counteract MSP filament assembly. We propose that MSP generates
      the protrusive force for its own vesicular export.

PMID- 15975937
TI  - Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia
      formation.
AB  - Choroid plexus (CP) produces the cerebrospinal fluid (CSF) of the central nervous
      system (CNS), but little is known about the mechanisms underlying development of
      this important tissue. CP forms in the hindbrain (4th ventricle), diencephalon
      (3rd ventricle) and dorsomedial telencephalon bilaterally (lateral ventricles).
      All of these sites lie at or near the embryonic dorsal midline (DM), which acts
      as a CNS patterning center. We therefore examined DM-CP relationships using
      normal and Gdf7 (Bmp12) transgenic embryos to fate map or ablate DM cells. These
      studies revealed a Gdf7 fate map that includes most CP epithelial (CPe) cells of
      the hindbrain and diencephalon. In the telencephalon, Gdf7 cell lineages were
      found in the small anterior domain of telencephalic CPe (tCPe), but its large
      posterior domain was devoid of these lineages. Anterior and posterior tCPe
      domains, which arise within a contiguous field separate from diencephalic CPe,
      also exhibited different patterns of apoptosis. Despite lacking Gdf7 cell
      lineages, the posterior tCPe domain failed to form after ablating Gdf7-expressing
      DM cells at neural tube stages. The tCPe loss was associated with abrogation of
      high-level bone morphogenetic protein (Bmp) signaling, which is known to be
      required for tCPe induction. Taken together, these studies demonstrate intimate
      DM-CPe relationships throughout the CNS and highlight two distinct tCPe domains,
      including a posterior domain whose genesis depends on DM cells in a non-cell
      autonomous fashion.

PMID- 15975938
TI  - Abnormalities in cartilage and bone development in the Apert syndrome
      FGFR2(+/S252W) mouse.
AB  - Apert syndrome is an autosomal dominant disorder characterized by malformations
      of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W
      mutation in fibroblast growth factor receptor 2 (FGFR2). To study the
      pathogenesis of this condition, we generated a knock-in mouse model with this
      mutation. The Fgfr2(+/S252W) mutant mice have abnormalities of the skeleton, as
      well as of other organs including the brain, thymus, lungs, heart and intestines.
      In the mutant neurocranium, we found a midline sutural defect and
      craniosynostosis with abnormal osteoblastic proliferation and differentiation. We
      noted ectopic cartilage at the midline sagittal suture, and cartilage
      abnormalities in the basicranium, nasal turbinates and trachea. In addition, from
      the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed
      chondrocytes, which were absent in the controls. Our results suggest that altered
      cartilage and bone development play a significant role in the pathogenesis of the
      Apert syndrome phenotype.

PMID- 15975939
TI  - Matrix metalloproteinases are required for retinal ganglion cell axon guidance at
      select decision points.
AB  - Axons receive guidance information from extrinsic cues in their environment in
      order to reach their targets. In the frog Xenopus laevis, retinal ganglion cell
      (RGC) axons make three key guidance decisions en route through the brain. First,
      they cross to the contralateral side of the brain at the optic chiasm. Second,
      they turn caudally in the mid-diencephalon. Finally, they must recognize the
      optic tectum as their target. The matrix metalloproteinase (MMP) and a
      disintegrin and metalloproteinase (ADAM) families are zinc (Zn)-dependent
      proteolytic enzymes. The latter functions in axon guidance, but a similar role
      has not yet been identified for the MMP family. Our previous work implicated
      metalloproteinases in the guidance decisions made by Xenopus RGC axons. To test
      specifically the importance of MMPs, we used two different in vivo exposed brain
      preparations in which RGC axons were exposed to an MMP-specific pharmacological
      inhibitor (SB-3CT), either as they reached the optic chiasm or as they extended
      through the diencephalon en route to the optic tectum. Interestingly, SB-3CT
      affected only two of the guidance decisions, with misrouting defects at the optic
      chiasm and tectum. Only at higher concentrations was RGC axon extension also
      impaired. These data implicate MMPs in the guidance of vertebrate axons, and
      suggest that different metalloproteinases function to regulate axon behaviour at
      distinct choice points: an MMP is important in guidance at the optic chiasm and
      the target, while either a different MMP or an ADAM is required for axons to make
      the turn in the mid-diencephalon.

PMID- 15975940
TI  - Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain
      formation in Xenopus embryos.
AB  - To address the patterning function of the Bmp2, Bmp4 and Bmp7 growth factors, we
      designed antisense morpholino oligomers (MO) that block their activity in Xenopus
      laevis. Bmp4 knockdown was sufficient to rescue the ventralizing effects caused
      by loss of Chordin activity. Double Bmp4 and Bmp7 knockdown inhibited tail
      development. Triple Bmp2/Bmp4/Bmp7 depletion further compromised trunk
      development but did not eliminate dorsoventral patterning. Unexpectedly, we found
      that blocking Spemann organizer formation by UV treatment or beta-Catenin
      depletion caused BMP inhibition to have much more potent effects, abolishing all
      ventral development and resulting in embryos having radial central nervous system
      (CNS) structures. Surprisingly, dorsal signaling molecules such as Chordin,
      Noggin, Xnr6 and Cerberus were not re-expressed in these embryos. We conclude
      that BMP inhibition is sufficient for neural induction in vivo, and that in the
      absence of ventral BMPs, Spemann organizer signals are not required for brain
      formation.

PMID- 15975941
TI  - Hand is a direct target of Tinman and GATA factors during Drosophila
      cardiogenesis and hematopoiesis.
AB  - The existence of hemangioblasts, which serve as common progenitors for
      hematopoietic cells and cardioblasts, has suggested a molecular link between
      cardiogenesis and hematopoiesis in Drosophila. However, the molecular mediators
      that might link hematopoiesis and cardiogenesis remain unknown. Here, we show
      that the highly conserved basic helix-loop-helix (bHLH) transcription factor Hand
      is expressed in cardioblasts, pericardial nephrocytes and hematopoietic
      progenitors. The homeodomain protein Tinman and the GATA factors Pannier and
      Serpent directly activate Hand in these cell types through a minimal enhancer,
      which is necessary and sufficient to drive Hand expression in these different
      cell types. Hand is activated by Tinman and Pannier in cardioblasts and
      pericardial nephrocytes, and by Serpent in hematopoietic progenitors in the lymph
      gland. These findings place Hand at a nexus of the transcriptional networks that
      govern cardiogenesis and hematopoiesis, and indicate that the transcriptional
      pathways involved in development of the cardiovascular, excretory and
      hematopoietic systems may be more closely related than previously appreciated.

PMID- 15975942
TI  - Brain abnormalities underlying altered activation in dyslexia: a voxel based
      morphometry study.
AB  - Voxel-based morphometry was used to assess the consistency among functional
      imaging and brain morphometry data in developmental dyslexia. Subjects, from
      three different cultural contexts (UK, France and Italy), were the same as those
      described in a previous PET activation paper, which revealed a common pattern of
      reduced activation during reading tasks in the left temporal and occipital lobes.
      We provide evidence that altered activation observed within the reading system is
      associated with altered density of grey and white matter of specific brain
      regions, such as the left middle and inferior temporal gyri and the left arcuate
      fasciculus. This supports the view that dyslexia is associated with both local
      grey matter dysfunction and with altered connectivity among phonological/reading
      areas. The differences were replicable across samples confirming that the
      neurological disorder underlying dyslexia is the same across the cultures
      investigated in the study.

PMID- 15975943
TI  - Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?
AB  - Multiple sclerosis afflicts more than 1 million individuals worldwide and is
      widely considered to be an autoimmune disease. Traditionally, CD4(+) T helper
      cells have almost exclusively been held responsible for its immunopathogenesis,
      partly because certain MHC class II alleles clearly predispose for developing
      multiple sclerosis and also, because of their importance in inducing experimental
      autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis.
      However, several strategies that target CD4(+) T cells beneficially in EAE have
      failed to ameliorate disease activity in multiple sclerosis, and some have even
      triggered exacerbations. Recently, the potential importance of CD8(+) T cells has
      begun to emerge. Physiologically, CD8(+) T cells are essential for detecting and
      eliminating abnormal cells, whether infected or neoplastic. In multiple
      sclerosis, genetic associations with MHC class I alleles have now been
      established, and CD8(+) as well as CD4(+) T cells have been found to invade and
      clonally expand in inflammatory central nervous system plaques. Recent animal
      models induced by CD8(+) T cells show interesting similarities to multiple
      sclerosis, in particular, in lesion distribution (more inflammation in the brain
      relative to the spinal cord), although not all of the features of the human
      disease are recapitulated. Here we outline the arguments for a possible role for
      CD8(+) T cells, a lymphocyte subset that has long been underrated in multiple
      sclerosis and should now be considered in new therapeutic approaches.

PMID- 15975944
TI  - Better without (lateral) frontal cortex? Insight problems solved by frontal
      patients.
AB  - A recently proposed theory on frontal lobe functions claims that the prefrontal
      cortex, particularly its dorso-lateral aspect, is crucial in defining a set of
      responses suitable for a particular task, and biasing these for selection. This
      activity is carried out for virtually any kind of non-routine tasks, without
      distinction of content. The aim of this study is to test the prediction of
      Frith's 'sculpting the response space' hypothesis by means of an 'insight'
      problem-solving task, namely the matchstick arithmetic task. Starting from
      Knoblich et al.'s interpretation for the failure of healthy controls to solve the
      matchstick problem, and Frith's theory on the role of dorsolateral frontal
      cortex, we derived the counterintuitive prediction that patients with focal
      damage to the lateral frontal cortex should perform better than a group of
      healthy participants on this rather difficult task. We administered the
      matchstick task to 35 patients (aged 26-65 years) with a single focal brain
      lesion as determined by a CT or an MRI scan, and to 23 healthy participants (aged
      34-62 years). The findings seemed in line with theoretical predictions. While
      only 43% of healthy participants could solve the most difficult matchstick
      problems ('type C'), 82% of lateral frontal patients did so (Fisher's exact test,
      P < 0.05). In conclusion, the combination of Frith's and Knoblich et al.'s
      theories was corroborated.

PMID- 15975945
TI  - Deficits of motion integration and segregation in patients with unilateral
      extrastriate lesions.
AB  - Functional neuroimaging in human subjects and single cell recordings in monkeys
      show that several extra-striate visual areas are activated by visual motion.
      However, the extent to which different types of motion are processed in different
      regions remains unclear, although neuropsychological studies of patients with
      circumscribed lesions hint at regional specialization. We, therefore, studied
      four patients with unilateral damage to different regions of extrastriate visual
      cortex on a series of visual discrimination tasks that required them, to a
      different extent, to integrate local motion signals in order to correctly
      perceive the direction of global motion. Performance was assessed
      psychophysically and compared with that of control subjects and with the
      patients' performance with stimuli presented in the visual field ipsilateral to
      the lesion. The results indicate considerable regional specialization in extra
      striate regions for different aspects of motion processing, namely the largest
      displacement from frame to frame (D-max) that can sustain perception of coherent
      motion; perception of relative speed; the amount of coherent motion needed to
      sustain a percept of global motion in a particular direction; the detection of
      discontinuities within a moving display; the extraction of form from motion. It
      was also clear that a defect in local motion, i.e. D-max, can be overcome by
      integrating local motion signals over a longer period of time. Although no
      patient suffered from only one defect, the overall pattern of results strongly
      supports the notion of regional specialization for different aspects of motion
      processing.

PMID- 15975947
TI  - Implicit memory and Alzheimer's disease neuropathology.
AB  - Explicit memory failure is the defining cognitive feature of Alzheimer's disease
      and relates to the hallmark neuropathological features (plaques and tangles) of
      this illness. However, a pattern of preserved and impaired implicit memory has
      been found in Alzheimer's disease patients that may be explained by the
      association between the processing demands of certain implicit tests and the
      level of regional Alzheimer's disease neuropathology. In this study, we tested
      the hypothesis that these neuropathological features are related to implicit
      memory--measured by repetition priming--in a test that emphasized conceptual (or
      meaning-based) cognitive processing, and that the pathological changes are not
      related to implicit memory in a repetition priming test that emphasized
      perceptual (or sensory-based) cognitive processing. Subjects were older nuns,
      priests and brothers participating in the Religious Orders Study who agreed to
      annual neurological and neuropsychological evaluation for Alzheimer's disease and
      common neurological conditions of ageing, and brain autopsy at time of death.
      Explicit memory was measured by seven tests of episodic recall and recognition
      and converted to a previously established summary measure. Implicit memory was
      measured by four repetition priming tests. One test, category exemplar priming,
      emphasized conceptual, or meaning-based cognitive processing. A second test, word
      identification priming, emphasized perceptual, or sensory-based cognitive
      processing. Two additional priming tests, picture-naming and word-stem
      completion, invoke both conceptual and perceptual processes. Neuritic and diffuse
      plaques, and neurofibrillary tangles identified by Bielschowsky silver stain,
      were quantified from five regions separately (frontal, parietal, temporal,
      entorhinal cortex and the hippocampus) and converted to a previously established
      summary measure. In linear regression analyses--controlling for age, sex and
      education--higher levels of Alzheimer's disease neuropathology were related to
      lower levels of explicit memory proximate to death. Higher levels of
      neuropathology were also related to lower levels of priming on the category
      exemplar test, but were not related to levels of priming on the word
      identification, picture-naming, or word-stem completion tests. The results
      suggest that hallmark indices of Alzheimer's disease neuropathology are
      associated with performance on priming tests to the extent that conceptual, but
      not perceptual, processing resources are required.

PMID- 15975946
TI  - Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with
      4 years follow-up.
AB  - Deep brain stimulation (DBS) is associated with significant improvement of motor
      complications in patients with severe Parkinson's disease after some 6-12 months
      of treatment. Long-term results in a large number of patients have been reported
      only from a single study centre. We report 69 Parkinson's disease patients
      treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus
      pallidus internus (GPi, n = 20) included in a multicentre study. Patients were
      assessed preoperatively and at 1 year and 3-4 years after surgery. The primary
      outcome measure was the change in the 'off' medication score of the Unified
      Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation
      of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of
      the 'off' medication UPDRS-III score at 3-4 years with respect to baseline.
      Stimulation improved cardinal features and activities of daily living (ADL) (P <
      0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time
      spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of
      levodopa was significantly reduced (35%) in the STN-treated group only (P <
      0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4
      years showed a significant worsening in the 'on' medication motor states of the
      UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural
      stability in the STN-treated group. Adverse events (AEs) included cognitive
      decline, speech difficulty, instability, gait disorders and depression. These
      were more common in patients treated with DBS of the STN. No patient abandoned
      treatment as a result of these side effects. This experience, which represents
      the first multicentre study assessing the long-term efficacy of either STN or GPi
      stimulation, shows a significant and substantial clinically important therapeutic
      benefit for at least 3-4 years in a large cohort of patients with severe
      Parkinson's disease.

PMID- 15975948
TI  - Functional MRI of the pre-ictal state.
AB  - The mechanisms underlying the transition from interictal to ictal states are
      poorly understood. Non-linear mathematical analysis of EEG frequency components
      has confirmed the presence of a pre-ictal state in focal epilepsy. We report on
      functional MRI (fMRI) analysis of the pre-ictal state in three patients with
      intractable focal epilepsy. Each subject had a typical partial seizure in the
      scanner while continuous blood oxygen level dependent (BOLD) fMRI images were
      acquired. The pre-ictal BOLD changes were first analysed by statistically
      comparing BOLD signals of two one-minute blocks. Further examination of the full
      time course was then performed. Each patient showed highly significant, focal
      BOLD signal changes. In Patient 1, a striking pre-ictal BOLD signal increase was
      seen over the region of the seizure focus identified on complementary epilepsy
      investigations. No significant BOLD signal decreases were observed. Patient 2
      showed widespread pre-ictal BOLD increase contralateral to the presumed seizure
      focus, as well as a focal BOLD decrease near the presumed seizure focus. In
      Patient 3, pre-ictal BOLD increase was co-localized with the site of
      hyperperfusion seen on ictal single photon emission computed tomography (SPECT).
      However, this was contralateral to the seizure focus localization based on
      seizure symptomatology. No significant BOLD decreases were seen. The time course
      data in each patient studied showed change of the BOLD signal several minutes
      before the onset of the seizure. Highly significant BOLD fMRI signal changes
      occur before the onset of seizures, supporting the presence of a pre-ictal state.
      These changes can be localized to the site of the presumed seizure focus, as well
      as to other brain regions, suggesting that the pre-ictal BOLD signal changes and
      their underlying mechanisms are complex.

PMID- 15975949
TI  - Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis.
AB  - In order to clarify the role of angiogenic factors in polyneuropathy of POEMS
      (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin
      changes) syndrome, we measured the serum concentrations of vascular endothelial
      growth factor (VEGF) and erythropoietin (EPO) in 11 patients and correlated these
      with VEGF and EPO peripheral nerve expression and the degree of endoneurial
      vessel involvement. We found that POEMS syndrome was associated with high levels
      of serum VEGF and, conversely, low levels of serum EPO. Similarly, in POEMS
      nerves VEGF was highly expressed in blood vessels and some non-myelin-forming
      Schwann cells. In contrast, the expression of VEGF receptor 2 was down-regulated
      compared with that in normal nerves. Both EPO and EPO receptor were localized to
      the nerve vasculature and were expressed to similar extents in normal and POEMS
      nerves. The inverse correlation between VEGF and EPO serum levels was maintained
      during the clinical course; however, both levels returned to normal when there
      was a response to therapy. High serum VEGF, low serum EPO and high peripheral
      nerve VEGF were all associated with more severe endoneurial vessel involvement
      and nerve damage. Light microscopy showed an increased thickness of the basal
      lamina and a narrowing of the lumina of endoneurial vessels in POEMS samples,
      while proliferation of endothelial cells and opening of tight junctions were
      observed by electron microscopy. The present data support the role of angiogenic
      factors as diagnostic and prognostic markers of POEMS syndrome. They also suggest
      that VEGF and EPO are involved in the pathogenesis of polyneuropathy. In
      conclusion, establishing the role of angiogenic factors in polyneuropathy may
      lead to a better understanding of the effects of VEGF and EPO on microangiopathy
      and Schwann cell function.

PMID- 15975950
TI  - A possible contributor to the higher degree of girls reporting psychological
      symptoms compared with boys in grade nine?
AB  - BACKGROUND: It is a recurrent finding that adolescent girls report psychological
      symptoms in a higher degree compared with boys. The explanations for this
      difference vary, but the psychosocial school environment has never been a focus
      in these explanations. The aim of this study was to analyse whether psychosocial
      factors at school were associated with a high degree of psychological symptoms
      among boys and girls in grade nine, with a special focus on sexual harassment.
      METHODS: The study was based on a cross-sectional study including 336 pupils (175
      girls and 161 boys) in grade nine (about 15 years old), who answered an extensive
      questionnaire. The non-response rate was negligible (<1%). Logistic regression
      analysis was used to analyse whether school-related factors (teacher support,
      classmate support, sexual harassment), body image, and parental support were
      associated with a high degree of psychological symptoms. RESULTS: Sexual
      harassment at school was associated with a high degree of psychological symptoms
      among girls. CONCLUSIONS: Sexual harassment must be acknowledged as a negative
      psychosocial school environmental factor of importance for the high degree of
      psychological ill-health symptoms among girls compared with boys.

PMID- 15975951
TI  - Original approach to the individual characteristics associated with forgone
      healthcare: a study in underprivileged areas, Paris region, France, 2001-2003.
AB  - BACKGROUND: The social inequalities in health have endured or even worsened
      comparatively throughout different social groups since the 1990s. Our objective
      was to identify the individual characteristics (socio-economic status, living
      conditions, individuals' social integration, health beliefs, expectations and
      representation and psychological characteristics) statistically associated with
      the fact of stating (or not) that healthcare had been forgone because of cost.
      METHODS: In this cross-sectional, multi-centre study we randomly selected a study
      sample from five underprivileged areas in the Paris region. A multiple logistic
      regression model was used to calculate the odds ratios (OR) and 95% confidence
      interval (CI). The validity of the model was assessed by goodness-of-fit tests
      (Pearson and deviance) and by the study of 100 bootstrap samples. RESULTS: After
      making adjustments for numerous individual socio-economic and health
      characteristics, we observed a higher occurrence of reported forgone healthcare
      among people who have had financial worries during adulthood [ORyes/no=5.47 (1.44
      20.75)], a life-course experience of physical, sexual or psychological abuse
      [ORyes/no=2.86 (1.40-5.84)]; who have experienced childhood difficulties
      [OR1/never difficulties=5.28 (1.81-15.39), OR2-4/never=7.62 (2.69-21.57),
      OR>4/never=8.57 (2.39-30.80)]; who have expressed a low degree of sickness
      orientation [OR(low/high)=2.62 (1.33-5.14)], a high worry/concern about health
      [ORhigh/low=2.71 (1.33-5.50)] and a low self-esteem [ORmedium/high=8.28 (1.44
      47.64), ORlow/high=16.44 (2.81-96.24)]. CONCLUSION: Aside from purely financial
      hurdles, other factors play a role in the non-use of healthcare services. Health
      policies mainly promoting equal financial access to healthcare have little chance
      of abating health inequalities.

PMID- 15975952
TI  - Epidemiological trend in tuberculosis in the Italian region of Liguria: impact of
      immigration and AIDS.
AB  - BACKGROUND: Tuberculosis (TB) uniformly decreased in all industrialized countries
      from 1950 to 1985. However, since 1985 an upsurge of the disease has been
      observed, probably due to the increases in AIDS and immigration. It is for this
      reason that in the last decade all industrialized countries have intensified
      their controls on TB and a new reduction has been recently observed. METHODS: In
      this study we collected epidemiological data (mortalities and reported cases) for
      the region of Liguria over the last 15 years. We then calculated the incidence
      rate of TB per 100,000 residents according to age, HIV infection and nationality,
      making a distinction between European Union (EU) citizens and immigrants coming
      from countries outside the EU. RESULTS: The rate of mortality, after the last
      peak at the end of the Second World War, has progressively decreased from 1946 to
      today, so much so that presently we record fewer than two cases per 100,000
      people. We observed a consistent downward trend in the incidence rate up to 1987,
      but from 1988 onwards this trend stopped and, in subsequent years, we detected an
      increase in the incidence rate, which peaked in 1996. This led to increased
      interventions, which has resulted in a considerably decreased overall rate of
      cases of TB during the last few years. The number of TB cases specifically among
      foreigners increased considerably during the last 5 years, whereas there was a
      drastic reduction in the number of total TB cases, as well as an interesting
      reduction in AIDS cases. During the same period there was a progressive decrease
      in tuberculin skin positivity in all school classes. CONCLUSIONS: The reduction
      in TB notifications is probably due to an increase in surveillance and control of
      social and health conditions. These results show that immigrant workers are
      considered to be a high-risk group, whereas the risk has progressively decreased
      in the HIV group.

PMID- 15975953
TI  - The new EU cigarette health warnings benefit smokers who want to quit the habit:
      results from the Dutch Continuous Survey of Smoking Habits.
AB  - BACKGROUND: As of September 2004, all European Union countries are required to
      have new health warnings on cigarette packs. This study examined the self
      perceived impact of these warnings on the attractiveness of cigarettes, smokers'
      motivation to quit and smoking behaviour. METHODS: This was a cross-sectional
      study comprising 3937 Dutch adult smokers. RESULTS: Of smokers, 14% became less
      inclined to purchase cigarettes because of the new warnings, 31.8% said they
      prefer to purchase a pack without the new warnings, 17.9% reported that warnings
      increased their motivated to quit and 10.3% said they smoked less. A strong dose
      response relationship was observed between these effects and intention to quit.
      CONCLUSIONS: The new warnings made cigarette packs less attractive, especially to
      smokers who already intended to stop smoking.

PMID- 15975954
TI  - Income inequality and mortality in Italy.
AB  - BACKGROUND: The relationship between income inequality and health remains
      controversial in terms of whether or not it exists and, if so, its extent and the
      mechanisms involved. This study examines the relationship between income
      inequality, as indicated by the Gini coefficient, and mortality in Italy.
      METHODS: Cross-sectional ecological study on the 57,138,489 inhabitants living in
      the 95 provinces existing in Italy in 1994. Multivariate weighted regression
      analysis of total and age-specific mortality, income inequality, gender, and
      interaction between income inequality and median income or geographical area.
      RESULTS: A positive association between income inequality and total mortality was
      observed for both genders in provinces with a low per capita income and in
      Southern and Central Italy. The effect was present for infants and for persons
      over 24 years of age; it was marked for the elderly, particularly women. A
      negative association with mortality was observed for males living in the North
      west. Interactions between income inequality and median income, and between
      income inequality and geographical area were found. CONCLUSION: In Italy, the
      relationship between income inequality and health is mixed and not universal, in
      so far as a positive association was observed only in provinces with lower
      absolute income. Elderly persons living in Southern Italy represent the
      population subgroup most vulnerable to unequal income distribution. Income
      inequality can, in part, explain the historically higher mortality among women in
      Southern Italy compared to women in the North. These results indicate that income
      inequality affects the health of population subgroups differentially.

PMID- 15975955
TI  - European patients' views on the responsiveness of health systems and healthcare
      providers.
AB  - BACKGROUND: Responsiveness to patients is now seen as a key characteristic of
      effective health systems. This study aimed to learn more about European people's
      views on the responsiveness of their country's health systems and healthcare
      providers. METHODS: Telephone survey with random samples of the populations in
      Germany, Italy, Poland, Slovenia, Spain, Sweden, Switzerland and the UK using
      random digit dialling. RESULTS: Responses were obtained from 8119 people aged 16
      and over. Just over half the respondents said that doctors always listened
      carefully to them, gave them time for questions and provided clear explanations.
      Respondents from Switzerland and the UK reported consistently high rates of
      satisfaction with doctors' communication skills, while respondents from Poland
      were significantly less satisfied. Younger people were more critical than older
      people. Expectations of patient involvement in treatment decisions were high,
      particularly among younger people, with 74% indicating a desire to be actively
      involved. Most respondents felt they should have a choice of primary care doctor,
      specialist doctor and hospital, but less than half felt they had sufficient
      information to make an informed choice. There were significant variations between
      the countries in reported levels of involvement and in satisfaction with
      opportunities for choice. CONCLUSIONS: The results suggest that many European
      patients want a more autonomous role in health care decision-making. Policy
      makers and clinicians should consider how to narrow the gap between public
      expectations and patients' experience.

PMID- 15975957
TI  - Association of death receptor 4 haplotype 626C-683C with an increased breast
      cancer risk.
AB  - Dysregulation of apoptosis plays a crucial role in carcinogenesis. Tumour
      necrosis factor-related apoptosis-inducing ligand stimulates the extrinsic
      apoptotic pathway by binding to death receptor 4 (DR4). Thus, genetic alterations
      within the candidate tumour suppressor gene DR4 would be expected to provoke a
      deficient apoptotic signalling thereby facilitating the development of cancer.
      The DR4 variants Thr209Arg and Glu228Ala were genotyped in a series of 521 breast
      cancer cases and 1100 control subjects from Germany, determining their impact on
      breast cancer risk. Neither Thr209Arg (626C>G) nor Glu228Ala (683A>C) alone were
      significantly associated with breast cancer risk [odds ratio (OR) = 0.84, 95%
      confidence interval (CI) = 0.65-1.08, P = 0.18 and OR = 0.89, 95% CI = 0.72-1.12,
      P = 0.30]. However, haplotype analysis revealed a 3.5-fold risk for carriers of
      the 626C-683C haplotype (OR = 3.52, 95% CI = 1.45-8.52, P = 0.003).

PMID- 15975956
TI  - Resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway
      as a central mechanism for S phase arrest in human ovarian carcinoma Ovcar-3
      cells.
AB  - Resveratrol is one of the most extensively studied cancer chemopreventive agents;
      however, its mechanisms of action are not completely understood. Here, we
      observed that resveratrol induces S phase arrest via Tyr15 phosphorylation of
      Cdc2 in human ovarian carcinoma Ovcar-3 cells. Overexpression of Cdc2AF, a mutant
      resistant to Thr14 and Tyr15 phosphorylation, ablated resveratrol-induced S phase
      arrest. Further upstream, we observed that resveratrol causes phosphorylation of
      cell division cycle 25C (Cdc25C) tyrosine phosphatase via the activation of
      checkpoint kinases Chk1 and Chk2, which in turn were activated via ATM (ataxia
      telangiectasia mutated)/ATR (ataxia telangiectasia-Rad3-related) kinase in
      response to DNA damage, as resveratrol also increased phospho-H2A.X (Ser139),
      which is known to be phosphorylated by ATM/ATR in response to DNA damage. The
      involvement of these molecules in resveratrol-induced S phase was also supported
      by the studies showing that addition of ATM/ATR inhibitor caffeine reverses
      resveratrol-caused activation of ATM/ATR-Chk1/2 as well as phosphorylation of
      Cdc25C, Cdc2 and H2A.X, and S phase arrest. In additional studies assessing
      whether observed effects of resveratrol are specific to Ovcar-3 cells, we
      observed that it also induces S phase arrest and H2A.X (Ser139) phosphorylation
      in other ovarian cancer cell lines PA-1 and SKOV-3, albeit at different levels;
      whereas, resveratrol showed only marginal S phase arrest in normal human foreskin
      fibroblasts with undetectable level of phospho-H2A.X (Ser139). These findings for
      the first time identify that resveratrol causes Cdc2-tyr15 phosphorylation via
      ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for DNA damage and S phase
      arrest selectively in ovarian cancer cells, and provide a rationale for the
      potential efficacy of ATM/ATR agonists in the prevention and intervention of
      cancer.

PMID- 15975959
TI  - Effect of administration of caffeine or green tea on the mutation profile in the
      p53 gene in early mutant p53-positive patches of epidermal cells induced by
      chronic UVB-irradiation of hairless SKH-1 mice.
AB  - Irradiation of SKH-1 mice with UVB light for 20 weeks resulted in a large number
      of patches of epidermal cells, which was visualized with an antibody that
      recognizes mutated p53 protein. Oral treatment of mice with caffeine (0.4 mg/ml)
      or green tea (6 mg tea solids/ml) as the drinking fluid during UVB irradiation
      decreased the number of patches by approximately 40%. Sequencing analysis of the
      p53 gene (exons 3 to 9) detected 88, 82 or 39 point mutations in 67, 70 or 29
      patches from water, caffeine or tea treated mice, respectively. A major hotspot
      at codon 270 (Arg-->Cys) accounted for 47.7% (water), 70.7% (caffeine) or 46.2%
      (tea) of all mutations. Patches from caffeine treated mice had fewer types of
      mutations than patches from mice treated with water or tea. Administration of
      caffeine or tea during 20 weeks of UVB irradiation eliminated mutations at codons
      149 (Pro-->Ser) and 210 (Arg-->Cys) but increased the frequency of mutations at
      codon 238 (Ser-->Phe). Topical applications of caffeine (1.2 mg in 100 microl
      acetone) once a day, five times a week for 6 weeks after stopping UVB decreased
      the number of patches by 63% when compared with mice treated with acetone. DNA
      sequencing analysis detected 63 and 68 mutations in 48 and 57 patches from
      acetone or caffeine treated mice, respectively. Although no differences in the
      frequency, position or types of mutations were observed, the caffeine group
      harbored less homozygous mutations (12.3% of the total) than the acetone group
      (31.3% of the total, P = 0.029). In summary, oral treatment of mice with caffeine
      or green tea during chronic UVB irradiation changed the mutation profile of the
      p53 gene in early mutant p53 positive epidermal patches, and topical applications
      of caffeine after discontinuation of chronic UVB irradiation specifically
      eliminated patches harboring homozygous p53 mutations.

PMID- 15975958
TI  - The role of docosahexaenoic acid in mediating mitochondrial membrane lipid
      oxidation and apoptosis in colonocytes.
AB  - Docosahexaenoic acid (DHA, 22:6 n-3) from fish oil, and butyrate, a fiber
      fermentation product, work coordinately to protect against colon tumorigenesis in
      part by inducing apoptosis. We have recently demonstrated that dietary DHA is
      incorporated into mitochondrial membrane phospholipids, thereby enhancing
      oxidative stress induced by butyrate metabolism. In order to elucidate the
      subcellular origin of oxidation induced by DHA and butyrate, immortalized young
      adult mouse colonocytes were treated with 0-200 microM DHA or linoleic acid (LA,
      18:2 n-6; control) for 72 h with or without 5 mM butyrate for the final 24 h.
      Cytosolic reactive oxygen species, membrane lipid oxidation, and mitochondrial
      membrane potential (MP), were measured by live-cell fluorescence microscopy.
      After 24 h of butyrate treatment, DHA primed cells exhibited a 151% increase in
      lipid oxidation (P < 0.01), compared with no butyrate treatment, which could be
      blocked by a mitochondria-specific antioxidant, 10-(6'-ubiquinoyl)
      decyltriphenylphosphonium bromide (MitoQ) (P < 0.05). Butyrate treatment of LA
      pretreated cells did not show any significant effect. In the absence of butyrate,
      DHA treatment, compared with LA, increased resting MP by 120% (P < 0.01). In
      addition, butyrate-induced mitochondrial membrane potential (MP), dissipation was
      21% greater in DHA primed cells as compared with LA at 6 h. This effect was
      reversed by preincubation with inhibitors of the mitochondrial permeability
      transition pore, cyclosporin A or bongkrekic acid (1 microM). The functional
      importance of these events is supported by the demonstration that DHA and
      butyrate-induced apoptosis is blocked by MitoQ. These data indicate that DHA and
      butyrate potentiate mitochondrial lipid oxidation and the dissipation of MP which
      contribute to the induction of apoptosis.

PMID- 15975960
TI  - All-trans and 9-cis retinoic acids, retinol and beta-carotene chemopreventive
      activities during the initial phases of hepatocarcinogenesis involve distinct
      actions on glutathione S-transferase positive preneoplastic lesions remodeling
      and DNA damage.
AB  - Chemopreventive activities of all-trans retinoic acid (AtRA), 9-cis retinoic acid
      (9cRA), retinol (ROL) and beta-carotene (betaC) were evaluated during
      hepatocarcinogenesis. Rats received 1 mg/100 g body wt AtRA (AtRA group), 9cRA
      (9cRA group), ROL (ROL group), 7 mg/100 g body wt betaC (betaC group) or corn oil
      (CO group, controls). Hepatocyte nodule incidence was reduced (P < 0.05) in betaC
      group (46%), but not (P > 0.05) in AtRA (92%), 9cRA (92%) and ROL (82%) groups,
      compared with the CO group (100%). Multiplicity of these preneoplastic lesions
      (PNL) was different (P < 0.05) between CO group (44 +/- 9) and 9cRA (11 +/- 4),
      ROL (7 +/- 3) and betaC (4 +/- 2) groups, except for AtRA group (27 +/- 9; P >
      0.05). Number/cm(2) liver section, mean area (mm(2)) and percent liver section
      area occupied by total (persistent + remodeling) placental glutathione S
      transferase (GST-P) positive PNL was reduced (P < 0.05) in AtRA (107 +/- 13; 0.12
      +/- 0.06; 13.9 +/- 3.9), 9cRA (71 +/- 12; 0.12 +/- 0.06; 6.8 +/- 2.2), ROL (96 +/
      13; 0.11 +/- 0.22; 6.8 +/- 2.0) and betaC (106 +/- 13; 0.08 +/- 0.03; 10.8 +/-
      2.5) groups compared with CO group (166 +/- 14; 0.18 +/- 0.09; 28.6 +/- 5.2).
      Percent of remodeling GST-P positive PNL was increased (P < 0.05) in 9cRA (92 +/-
      1), ROL (96 +/- 1) and betaC (93 +/- 1) groups, but not (P > 0.05) in AtRA group
      (90 +/- 2), compared with the CO group (86 +/- 1). Compared with the CO group,
      all groups present in PNL reduced (P < 0.05) cell proliferation and no
      differences (P > 0.05) in apoptosis. DNA damage [comet length (mum)] was reduced
      (P < 0.05) in ROL (87.9 +/- 2.6) and betaC (89.2 +/- 4.0) groups, but not in AtRA
      (94.8 +/- 4.1) and 9cRA (94.2 +/- 1.5) groups, compared with the CO group (100.4
      +/- 3.9). AtRA, 9cRA, ROL and betaC presented chemopreventive activities against
      hepatocarcinogenesis. These involve inhibition of cell proliferation, but not
      induction of apoptosis. Increased remodeling of GST-P positive PNL relates to
      9cRA, ROL and betaC actions, while inhibition of DNA damage relates to ROL and
      betaC actions.

PMID- 15975961
TI  - Hormesis and dose-response-mediated mechanisms in carcinogenesis: evidence for a
      threshold in carcinogenicity of non-genotoxic carcinogens.
AB  - Recently the idea of hormesis, a biphasic dose-response relationship in which a
      chemical exerts opposite effects dependent on the dose, has attracted interest in
      the field of carcinogenesis. With non-genotoxic agents there is considerable
      experimental evidence in support of hormesis and the present review highlights
      current knowledge of dose-response effects. In particular, several in vivo
      studies have provided support for the idea that non-genotoxic carcinogens may
      inhibit hepatocarcinogenesis at low doses. Here, we survey the examples and
      discuss possible mechanisms of hormesis using phenobarbital, 1,1-bis(p
      chlorophenyl)-2,2,2-trichloroethane (DDT), alpha-benzene hexachloride (alpha-BHC)
      and other non-genotoxins. Furthermore, the effects of low and high doses of non
      genotoxic and genotoxic compounds on carcinogenesis are compared, with especial
      attention to differences in mechanisms of action in animals and possible
      application of the dose-response concept to cancer risk assessment in humans.
      Epigenetic processes differentially can be affected by agents that impinge on
      oxidative stress, DNA repair, cell proliferation, apoptosis, intracellular
      communication and cell signaling. Non-genotoxic carcinogens may target nuclear
      receptors, cause aberrant DNA methylation at the genomic level and induce post
      translational modifications at the protein level, thereby impacting on the
      stability or activity of key regulatory proteins, including oncoproteins and
      tumor suppressor proteins. Genotoxic agents, in contrast, cause genetic change by
      directly attacking DNA and inducing mutations, in addition to temporarily
      modulating the gene activity. Carcinogens can elicit a variety of changes via
      multiple genetic and epigenetic lesions, contributing to cellular carcinogenesis.

PMID- 15975962
TI  - Activation of cPLA2 is required for leukotriene D4-induced proliferation in colon
      cancer cells.
AB  - It is well documented that prolonged inflammatory conditions, particularly those
      relating to the colon, have been shown to induce cancer. We have previously
      demonstrated that the pro-inflammatory mediator leukotriene D(4) (LTD(4)) induces
      survival and proliferation in intestinal cells and that its receptor, CysLT(1),
      is upregulated in human colon cancer tissue. Here we demonstrate, for the first
      time that in both Int 407 (a non-transformed human intestinal epithelial cell
      line) and Caco-2 cells (a human colorectal carcinoma cell line), cytosolic
      phospholipase A(2)alpha (cPLA(2)alpha) is activated and translocates to the
      nucleus upon LTD(4) stimulation via a calcium-dependent mechanism that involves
      activation of protein kinase C (PKC), and the mitogen-activated protein kinases
      ERK1/2 and p38. We also show with a cPLA(2)alpha promoter luciferase assay, that
      LTD(4) induces an increase in the transcriptional activity of cPLA(2)alpha via
      activation of cPLA(2)alpha and the transcription factor NFkappaB. Interestingly
      we demonstrate here that both the basal and the LTD(4)-induced cPLA(2)alpha
      activity is elevated approximately 3-fold in Caco-2 colon cancer cells compared
      with Int 407 cells. The difference in basal activity was confirmed in human colon
      tumor samples by the finding of a similar increase in cPLA(2)alpha activity when
      compared with normal colon tissue. A functional role of the increased
      cPLA(2)alpha activity in tumor cells was revealed by our findings that inhibition
      of this enzyme reduced both basal and LTD(4)-induced proliferation, the effects
      being most pronounced in Caco-2 tumor cells. The present data reveal that
      cPLA(2)alpha, an important intracellular signal activated by inflammatory
      mediators, is an important regulator of colon tumor growth.

PMID- 15975963
TI  - Mammary carcinoma provides highly tumourigenic and invasive reactive stromal
      cells.
AB  - The progression of a lesion to a carcinoma is dependent on the engagement of
      'reactive stroma' that provides structural and vascular support for tumour growth
      and also leads to tissue reorganization and invasiveness. The composition of
      reactive stroma closely resembles that of granulation tissue, and myofibroblasts
      are thought to play a critical role in driving the stromal reaction of invasive
      tumours as well as of physiological wound repair. In the present work, we
      established a myofibroblast-like cell line, named A17, from a mouse mammary
      carcinoma model in which tumourigenesis is triggered in a single step by the
      overexpression of HER-2/neu transgene in the epithelial compartment of mammary
      glands. We showed that although they derived from a tumour of epithelial origin
      and did not express HER-2/neu transgene, their subcutaneous injection into the
      backs of syngeneic mice gave rise to sarcomatoid tumours which expressed alpha
      smooth muscle actin at the invasive edge. The expression of cytokeratin 14
      suggested a myoepithelial origin but immunophenotypical profile, invasive and
      neoangiogenic potential of A17 cells and tumours showed many similarities with
      the reactive stroma that occurs in wound repair and in cancerogenesis. Our
      results suggest that epithelial tumours have the potential to develop highly
      tumourigenic and invasive reactive stromal cells and our cell line represents a
      novel, effective model for studying epithelial-stromal interaction and the role
      of myofibroblasts in tumour development.

PMID- 15975964
TI  - Efficacy and safety of switching from infliximab to adalimumab: a comparative
      controlled study.
AB  - OBJECTIVE: To describe the efficacy and safety of adalimumab in patients with
      rheumatoid arthritis (RA) who had previously discontinued infliximab treatment.
      METHODS: 24 patients with RA who discontinued treatment with infliximab
      (switchers) were treated with adalimumab (40 mg every 2 weeks, subcutaneously)
      for 12 months. The results were compared with those for 25 patients with RA
      receiving adalimumab who had not previously used an anti-tumour necrosis factor
      alpha inhibitor (controls). Disease activity was measured with the 28 joint count
      Disease Activity Score (DAS28), and clinical response with the American College
      of Rheumatology (ACR) 20% response criteria. RESULTS: At baseline there were no
      differences in demographic, clinical, and laboratory features between the two
      groups. After 12 months' adalimumab treatment, clinical improvement was similar
      in both groups. More specifically, ACR 20% response criteria were achieved by
      18/24 (75%) switchers and by 19/25 (76%) subjects in the control group. Four
      switchers discontinued the study-two because of adverse events and two because of
      lack of efficacy, while three control patients discontinued the study-one because
      of lack of efficacy and two owing to side effects. CONCLUSION: Adalimumab is a
      well tolerated and effective treatment for patients with RA, even when infliximab
      has been discontinued.

PMID- 15975965
TI  - Femorotibial and patellar cartilage loss in patients prior to total knee
      arthroplasty, heterogeneity, and correlation with alignment of the knee.
AB  - OBJECTIVE: To analyse tibial, femoral, and patellar cartilage loss in patients
      prior to total knee arthroplasty (TKA), and its correlation with alignment of the
      knee. METHODS: 26 patients (aged 58 to 86 years) with a clinical indication for
      TKA were investigated. Quantitative end points of cartilage morphology (T scores
      for cartilage volume normalised to total subchondral bone area) were determined
      from coronal and axial magnetic resonance image data, using proprietary software.
      The static alignment of the knee was determined from standing full limb
      radiographs. RESULTS: The magnitude of cartilage loss (T score of normalised
      cartilage volume) was highly variable within the knee, correlation coefficients
      ranging from r = 0.17 to 0.51 between cartilage plates. The correlation of
      cartilage loss with static alignment of the knee (as a continuous variable) was r
      = -0.52 (p<0.05) for the medial tibia, -0.38 (not significant) for the medial
      femur, +0.76 (p<0.001) for the lateral tibia, +0.31 (not significant) for the
      lateral femur, and -0.09 for the patella. When analysing alignment independent of
      direction (valgus or varus), the correlation for the patella increased to r =
      0.30, but remained non-significant. CONCLUSIONS: Cartilage loss was highly
      variable among patients and among cartilage plates before knee arthroplasty. Its
      correlation with alignment was stronger for the tibia than for the femur. There
      was some evidence for an association of alignment and patellar cartilage loss.
      These findings stimulate further research on the mechanism and cause-effect
      relation of alignment and knee osteoarthritis using quantitative magnetic
      resonance imaging technology.

PMID- 15975966
TI  - The effect of etanercept on anti-cyclic citrullinated peptide antibodies and
      rheumatoid factor in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the changes in anti-cyclic citrullinated peptide
      antibodies (anti-CCP) and rheumatoid factor (RF) following etanercept treatment
      in patients with rheumatoid arthritis. METHODS: The study included 90 patients
      with rheumatoid arthritis who failed treatment with disease modifying
      antirheumatic drugs (DMARDs). All patients were allowed to continue treatment
      with DMARDs; 52 of them received etanercept as a twice weekly 25 mg subcutaneous
      injection for three months, and the others did not. Serum samples were collected
      at baseline and one month intervals during the treatment course. The serum levels
      of anti-CCP and RF were tested by enzyme linked immunosorbent assay and
      nephelometry, respectively. RESULTS: At baseline, 45 of the 52 etanercept treated
      patients (86.5%) and 32 of the 38 controls (84.2%) were positive for anti-CCP.
      Tests for RF were positive in 78.9% and 84.2% of patients with or without
      etanercept treatment, respectively. The serum levels of anti-CCP and RF decreased
      significantly after a three month etanercept treatment (p = 0.007 and p = 0.006,
      respectively). The average decrease from baseline calculated for each individual
      patient in the etanercept treated group was 31.3% for anti-CCP and 36% for RF.
      The variation in anti-CCP was positively correlated with the variation in disease
      activity, swollen and tender joint counts, RF, and C reactive protein.
      CONCLUSIONS: Etanercept combined with DMARDs leads to a much greater decrease
      than DMARDs alone in the serum levels of anti-CCP and RF in rheumatoid arthritis,
      compatible with a reduction in clinical disease activity.

PMID- 15975967
TI  - Duration of rheumatoid arthritis influences the degree of functional improvement
      in clinical trials.
AB  - BACKGROUND: Functional capacity is an important outcome in rheumatoid arthritis
      and is generally measured using the Health Assessment Questionnaire disability
      index (HAQ). Functional limitation incorporates both activity and damage. Because
      irreversible damage increases over time, the HAQ may be less likely to show
      improvement in late than in early rheumatoid arthritis. OBJECTIVE: To determine
      the relation between sensitivity to change of the HAQ and duration of rheumatoid
      arthritis in reports of clinical trials. METHODS: Data were pooled from clinical
      trials that measured responses of HAQ scores at three or six months. The effect
      size of the HAQ was calculated and linear regression used to predict the effect
      size by duration of rheumatoid arthritis at group level. Treatment effect was
      adjusted for by including the effect sizes of pain scores and of tender joint
      counts as additional independent variables in separate models. Subgroup analysis
      employed contemporary regimens (methotrexate, leflunomide, combination therapies,
      and TNF inhibitors) only. RESULTS: 36 studies with 64 active treatment arms and
      7628 patients (disease duration 2.5 months to 12.2 years) were included. The
      effect sizes of the HAQ decreased by 0.02 for each additional year of mean
      disease duration using all trials, and by 0.04/year in the subgroup analysis
      (p<or=0.01 for both analyses, except for pain adjusted models at three months).
      CONCLUSIONS: In individual trials, less improvement in the HAQ might be expected
      in late than in early rheumatoid arthritis. Comparison of changes in HAQ among
      rheumatoid arthritis trials should take into consideration the disease stage of
      the treated groups.

PMID- 15975968
TI  - Raised plasma concentration and ex vivo production of inflammatory chemokines in
      patients with systemic lupus erythematosus.
AB  - BACKGROUND: Chemokines are involved in leucocyte chemotaxis. Infiltrating
      leucocytes play an important role of tissue injury in systemic lupus
      erythematosus (SLE). OBJECTIVE: To investigate the role of inflammatory
      chemokines and their association with interleukin 18 (IL18) in SLE pathogenesis
      and disease activity. METHODS: Plasma concentrations and ex vivo peripheral blood
      mononuclear cell production of inflammatory chemokines IP-10, RANTES, MIG, MCP-1,
      TARC, IL8, and GROalpha, and proinflammatory cytokines IL18, IFNgamma, IL2, IL4,
      and IL10 were assayed in 80 SLE patients with or without renal disease and 40
      healthy controls by immunofluorescence flow cytometry and enzyme linked
      immunosorbent assay. RESULTS: Plasma IP10, RANTES, MIG, MCP-1, GROalpha, and IL18
      concentrations in all SLE patients were higher than in controls, and correlated
      significantly with SLEDAI score (all p<0.05). In SLE patients without renal
      disease, IP10, RANTES, MIG, MCP-1, IL8, and IL18 correlated positively with
      SLEDAI score, while in those with renal derangement, IP10, IL8, IL10, and IL18
      correlated with disease activity (all p<0.05). Plasma IL18 concentration
      correlated positively with IP10, MIG, GROalpha, and IL8 in all SLE patients (all
      p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC,
      IFNgamma, IL4, and IL10 were higher in all SLE patients regardless of their
      difference in disease activity (all p<0.05). Patients with renal disease had an
      augmented ex vivo release of RANTES. CONCLUSIONS: The correlation of raised
      plasma concentration and ex vivo production of inflammatory chemokines with
      disease activity, and their association with IL18, supports the view that
      chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE
      pathogenesis.

PMID- 15975969
TI  - Effect of human vasoactive intestinal peptide gene transfer in a murine model of
      Sjogren's syndrome.
AB  - BACKGROUND: Sjogren's syndrome (SS), an autoimmune exocrinopathy mainly affecting
      lachrymal and salivary glands, results in ocular and oral dryness
      (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are
      largely unknown; currently, only palliative treatment is available. OBJECTIVE: To
      determine whether gene transfer of vasoactive intestinal peptide (VIP), based on
      its immunomodulatory properties, might be useful in the management of SS.
      METHODS: A recombinant serotype 2 adeno-associated virus encoding the human VIP
      transgene (rAAV2hVIP) was constructed and its efficacy tested in the female non
      obese diabetic (NOD) mouse model for SS after retrograde instillation in
      submandibular glands (SMGs). 10(10) particles/gland of rAAV2hVIP or rAAV2LacZ
      (encoding beta-galactosidase; control vector) were administered at 8 weeks of age
      (before sialadenitis onset). Salivary flow rates were determined before vector
      delivery and at time of death (16 weeks). After death, saliva, serum, and SMGs
      were harvested. Salivary output, inflammatory infiltrates (focus scores), VIP
      protein expression, cytokine profile, and serum anti-VIP antibodies were
      analysed. RESULTS: rAAV2hVIP significantly improved the salivary flow, increased
      SMG and serum expression of VIP, and reduced SMG cytokines interleukin (IL) 2,
      IL10, IL12 (p70), and tumour necrosis factor alpha, and serum RANTES, compared
      with the control vector. No difference in focus scores or apoptotic rates was
      found; neutralising antibodies were not detected. CONCLUSIONS: Local delivery of
      rAAV2hVIP can have disease modifying and immunosuppressive effects in SMGs of the
      NOD mouse model of SS. The new strategy of employing VIP prophylactically may be
      useful for both understanding and managing the salivary component of SS.

PMID- 15975970
TI  - Standardisation of synovial tissue infiltrate analysis: how far have we come? How
      much further do we need to go?
AB  - Changes in cellular infiltrate and expression of cytokines, chemokines, and cell
      adhesion molecules as a result of therapeutic interventions in rheumatoid
      arthritis can be demonstrated in the synovial membrane. However, before synovial
      tissue analysis can be used as an outcome measure in such studies,
      standardisation of the site and method of synovial tissue acquisition, methods of
      tissue processing, and appropriate methods of detection and measurement of cell
      lineage specific markers and relevant biological proteins is needed.

PMID- 15975971
TI  - Endothelial dysfunction in patients with rheumatoid arthritis is associated with
      a reduced number and impaired function of endothelial progenitor cells.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with increased morbidity and
      mortality attributable to accelerated atherosclerosis and cardiovascular events.
      OBJECTIVE: To determine the role played by endothelial progenitor cells (EPC) in
      the defence system against arteriosclerosis. METHODS: The number and function of
      EPC in 13 young patients with RA with low disease activity (DAS28 3.5 (0.3)) and
      13 healthy control subjects was studied. Endothelial function was investigated by
      agonist-induced, endothelium dependent vasodilatation measured by the forearm
      blood flow technique. Migratory activity and adhesion of EPC to tumour necrosis
      factor alpha (TNFalpha) activated mature endothelial cells and components of the
      extracellular matrix were tested in vitro. Putative precursor populations
      (CD34(+), CD34(+)/CD133(+), and CD34(+)/KDR(+) haematopoietic stem cells) were
      measured by flow cytometric analysis. RESULTS: Acetylcholine-induced, endothelium
      dependent vasodilatation was reduced by about 50% in patients with RA, indicating
      endothelial dysfunction, whereas endothelium-independent vasodilatation in
      response to glyceryl trinitrate was at control level. Significantly reduced
      numbers of EPC were found in the patients compared with controls. Migratory
      activity of EPC was decreased in patients with RA. Adhesion to mature endothelial
      cells after activation with TNFalpha was enhanced only in controls. The adhesion
      to matrix proteins and the number of putative precursor cell lineages was
      comparable in both groups. CONCLUSION: Endothelial dysfunction in patients with
      RA with low grade inflammation is associated with a reduced number and partial
      dysfunction of EPC. Further studies are needed to explore whether interventions
      that potentially ameliorate the number and function of EPC also improve
      endothelial function in these patients.

PMID- 15975972
TI  - Human nasal cartilage responds to oncostatin M in combination with interleukin 1
      or tumour necrosis factor alpha by the release of collagen fragments via
      collagenases.
AB  - BACKGROUND: The synergistic degradation of cartilage by oncostatin M (OSM) in
      combination with either interleukin 1 (IL1) or tumour necrosis factor alpha
      (TNFalpha) has been previously demonstrated using bovine nasal cartilage (BNC).
      OBJECTIVES: (a) To investigate if human nasal cartilage (HNC) responds in the
      same way as BNC to these cytokine combinations, particularly in collagen
      degradation. (b) To compare the response of human nasal and articular cartilages.
      METHODS: Collagen release was assessed by measuring the hydroxyproline content of
      culture supernatants and proteoglycan release by the dimethylmethylene blue
      assay. Matrix metalloproteinase (MMP)-1, MMP-13, and tissue inhibitor of
      metalloproteinase 1 release were measured by specific enzyme linked immunosorbent
      assays (ELISAs), and collagenolytic activity was measured by a bioassay using
      radiolabelled collagen. RESULTS: OSM in combination with either IL1 or TNFalpha
      acted synergistically to induce collagenolysis from HNC, with a maximum of 79%
      collagen release. This degradation strongly correlated with MMP-1 and MMP-13
      levels and collagenolytic activity. CONCLUSION: Collagen release from human
      cartilage is marked and implicates both MMP-1 and MMP-13 in the synergistic
      degradation of human cartilage by OSM in combination with either IL1 or TNFalpha.
      HNC responds in the same way as BNC, thus validating the bovine cartilage
      degradation assay as a model relevant to human disease.

PMID- 15975973
TI  - Stimulatory effects of distinct members of the bone morphogenetic protein family
      on ligament fibroblasts.
AB  - OBJECTIVE: To investigate effects of cartilage derived morphogenetic protein-1
      and -2 (CDMP-1, CDMP-2), bone morphogenetic protein (BMP)-7 and BMP-6 on
      metabolism of ligament fibroblasts and their osteogenic or chondrogenic
      differentiation potential. METHODS: Ligament fibroblasts were obtained from 3
      month old calves, plated as monolayers or micromass cultures, and incubated with
      or without CDMP-1, CDMP-2, BMP-7, and BMP-6. Expression of the indicated growth
      factors was assessed by RT-PCR and western immunoblotting. The presence of their
      respective type I and II receptors, and lineage related markers, was investigated
      in stimulated and unstimulated cells by RT-PCR and northern blotting.
      Biosynthesis of matrix proteoglycans was assessed by [(35)S]sulphate
      incorporation in monolayers. Alcian blue and toluidine blue staining was done in
      micromass cultures. RESULTS: CDMP-1, CDMP-2, BMP-7, and BMP-6 were detected on
      mRNA and on the protein level. Type I and II receptors were endogenously
      expressed in unstimulated ligament fibroblasts. The growth factors significantly
      stimulated total proteoglycan synthesis as assessed by [(35)S]sulphate
      incorporation. Toluidine blue staining showed cartilage-specific metachromasia in
      the growth factor treated micromass cultures. Transcription analysis of
      stimulated ligament fibroblasts demonstrated coexpression of chondrocyte markers
      but no up regulation of osteogenic markers. CONCLUSION: CDMP-1, CDMP-2, BMP-7,
      and BMP-6 and their receptors were expressed in ligament tissue. These growth
      factors induced matrix synthesis in fibroblasts derived from bovine ligament. The
      preferential expression of cartilage markers in vitro suggests that CDMP-1, CDMP
      2, BMP-7, and BMP-6 have the potential to induce differentiation towards a
      chondrogenic phenotype in ligament fibroblasts. Thus, fibroblasts from ligaments
      may serve as a source for chondrogenesis and tissue repair.

PMID- 15975974
TI  - Functional role of TRPC proteins in native systems: implications from knockout
      and knock-down studies.
AB  - Available data on transient receptor potential channel (TRPC) protein functions
      indicate that these proteins represent essential constituents of agonist
      activated and phospholipase C-dependent cation entry pathways in primary cells
      which contribute to the elevation of cytosolic Ca2+. In addition, a striking
      number of biological functions have already been assigned to the various TRPC
      proteins, including mechanosensing activity (TRPC1), chemotropic axon guidance
      (TRPC1 and TRPC3), pheromone sensing and the regulation of sexual and social
      behaviour (TRPC2), endothelial-dependent regulation of vascular tone, endothelial
      permeability and neurotransmitter release (TRPC4), axonal growth (TRPC5),
      modulation of smooth muscle tone in blood vessels and lung and regulation of
      podocyte structure and function in the kidney (TRPC6). The lack of compounds
      which specifically block or activate TRPC proteins impairs the analysis of TRPC
      function in primary cells. We therefore concentrate in this contribution on (i)
      studies of TRPC-deficient mouse lines, (ii) data obtained by gene-silencing
      approaches using antisense oligonucleotides or RNA interference, (iii) expression
      experiments employing dominant negative TRPC constructs, and (iv) recent data
      correlating mutations of TRPC genes associated with human disease.

PMID- 15975975
TI  - Direct inhibition of substantia gelatinosa neurones in the rat spinal cord by
      activation of dopamine D2-like receptors.
AB  - Dopaminergic innervation of the spinal cord is largely derived from the brain. To
      understand the cellular mechanisms of antinociception mediated by descending
      dopaminergic pathways, we examined the actions of dopamine (DA) on nociceptive
      transmission by using behavioural studies and whole-cell patch-clamp recordings
      from substantia gelatinosa (SG) neurones in the spinal cord. Intrathecal
      administration of DA increased the mechanical nociceptive threshold and this
      effect was mimicked by a D2-like receptor agonist, quinpirole, but not by a D1
      like receptor agonist, SKF 38393. In current-clamp mode of patch-clamp
      recordings, bath application of DA hyperpolarized the membrane potential of SG
      neurones and suppressed action potentials evoked by electrical stimulation of a
      dorsal root. In voltage-clamp mode, DA induced an outward current that was
      resistant to TTX, was blocked by the addition of Cs+ or GDP-beta-S in the pipette
      solution, and was inhibited in the presence of Ba+. The DA-induced current
      reversed its polarity at a potential close to the equilibrium potential of the K+
      channel calculated from the Nernst equation. The DA-induced outward current was
      mimicked by quinpirole, but not by SKF 38393. The DA-induced outward current was
      suppressed by a D2-like receptor antagonist, sulpiride, but not by a D1-like
      receptor antagonist, SCH 23390. In contrast, DA did not cause any significant
      change in amplitude and frequency of miniature excitatory postsynaptic currents
      (mEPSCs). These results indicate that DA mainly acts on postsynaptic SG neurones
      to induce an outward current via G-protein-mediated activation of K+ channels
      through D2-like receptors. This may be a possible mechanism for antinociception
      by the descending dopaminergic pathway.

PMID- 15975976
TI  - Descending vasa recta pericytes express voltage operated Na+ conductance in the
      rat.
AB  - We studied the properties of a voltage-operated Na+ conductance in descending
      vasa recta (DVR) pericytes isolated from the renal outer medulla. Whole-cell
      patch-clamp recordings revealed a depolarization-induced, rapidly activating and
      rapidly inactivating inward current that was abolished by removal of Na+ but not
      Ca+ from the extracellular buffer. The Na+ current (I(Na)) is highly sensitive to
      tetrodotoxin (TTX, Kd = 2.2 nM). At high concentrations, mibefradil (10 microM)
      and Ni+ (1 mM) blocked I(Na). I(Na) was insensitive to nifedipine (10 microM).
      The L-type Ca+ channel activator FPL-64176 induced a slowly
      activating/inactivating inward current that was abolished by nifedipine.
      Depolarization to membrane potentials between 0 and 30 mV induced inactivation
      with a time constant of approximately 1 ms. Repolarization to membrane potentials
      between -90 and -120 mV induced recovery from inactivation with a time constant
      of approximately 11 ms. Half-maximal activation and inactivation occurred at 
      23.9 and -66.1 mV, respectively, with slope factors of 4.8 and 9.5 mV,
      respectively. The Na+ channel activator, veratridine (100 microM), reduced peak
      inward I(Na) and prevented inactivation. We conclude that a TTX-sensitive voltage
      operated Na+ conductance, with properties similar to that in other smooth muscle
      cells, is expressed by DVR pericytes.

PMID- 15975977
TI  - Effects of two protocols of intermittent hypoxia on human ventilatory,
      cardiovascular and cerebral responses to hypoxia.
AB  - We determined the ventilatory, cardiovascular and cerebral tissue oxygen response
      to two protocols of normobaric, isocapnic, intermittent hypoxia. Subjects (n =
      18, male) were randomly assigned to short-duration intermittent hypoxia (SDIH,
      12% O2 separated by 5 min of normoxia for 1 h) or long-duration intermittent
      hypoxia (LDIH, 30 min of 12% O2). Both groups had 10 exposures over a 12 day
      period. The hypoxic ventilatory response (HVR) was measured before each daily
      intermittent hypoxia exposure on days 1, 3, 5, 8, 10 and 12. The HVR was measured
      again 3 and 5 days after the end of intermittent hypoxia. During all procedures,
      ventilation, blood pressure, heart rate, arterial oxyhaemoglobin saturation and
      cerebral tissue oxygen saturation were measured. The HVR increased throughout
      intermittent hypoxia exposure regardless of protocol, and returned to baseline by
      day 17 (day 1, 0.84 +/- 0.50; day 12, 1.20 +/- 1.01; day 17, 0.95 +/- 0.58 l min(
      1) %S(aO2)(-1); P < 0.01). The change in systolic blood pressure sensitivity (r =
      +0.68; P < 0.05) and the change in diastolic blood pressure sensitivity (r =
      +0.73; P < 0.05) were related to the change in HVR, while the change in heart
      rate sensitivity was not (r = +0.32; NS). The change in cerebral tissue oxygen
      saturation sensitivity to hypoxia was less on day 12, and returned to baseline by
      day 17 (day 1, -0.51 +/- 0.13; day 12, -0.64 +/- 0.18; day 17, -0.51 +/- 0.13; P
      < 0.001). Acute exposure to SDIH increased mean arterial pressure (+5 mmHg; P <
      0.01), but LDIH did not (P > 0.05). SDIH and LDIH had similar effects on the
      ventilatory and cardiovascular response to acute progressive hypoxia and hindered
      cerebral oxygenation. Our findings indicate that the vascular processes required
      to control blood flow and oxygen supply to cerebral tissue in a healthy human are
      hindered following exposure to 12 days of isocapnic intermittent hypoxia.

PMID- 15975978
TI  - Synergistic interactions between Ca2+ entries through L-type Ca2+ channels and
      Na+-Ca2+ exchanger in normal and failing rat heart.
AB  - We used confocal Ca2+ imaging and the patch-clamp technique to investigate the
      interplay between Ca2+ entries through L-type Ca2+ channels (LCCs) and reverse
      mode Na+-Ca2+ exchange (NCX) in activating Ca2+-induced Ca2+ release (CICR) from
      the sarcoplasmic reticulum (SR) in cardiac myocytes from normal and failing rat
      hearts. In normal myocytes exposed to N(6),2'-O-dibutyryl adenosine-3',5'-cyclic
      monophosphate (db-cAMP, membrane-permeable form of cAMP), the bell-shaped voltage
      dependence of cytosolic Ca2+ transients was dramatically broadened due to
      activation of SR Ca2+ release at high membrane potentials (30-120 mV). This
      broadening of Ca2+-transient voltage dependence could be prevented by KB-R7943,
      an inhibitor of the reverse-mode NCX. Trans-sarcolemmal Ca2+ entries were
      measured fluorometrically in myocytes during depolarizing steps to high membrane
      potentials. The total Ca2+ entry (deltaF(Tot)) was separated into two Ca2+ entry
      components, LCC-mediated (deltaF(LCC)) and NCX-mediated (deltaF(NCX)), by
      exposing the cells to the specific inhibitors of LCCs and reverse-mode NCX,
      nifedipine and KB-R7943, respectively. In the absence of protein kinase A (PKA)
      stimulation the amplitude of the Ca2+-inflow signal (deltaF(Tot)) corresponded to
      the arithmetic sum of the amplitudes of the KB-R7943- and nifedipine-resistant
      components (deltaF(Tot)=deltaF(LCC)+deltaF(NCX)). PKA activation resulted in
      significant increases in deltaF(Tot) and deltaF(LCC). Paradoxically, deltaF(Tot)
      became approximately threefold larger than the sum of the deltaF(NCX) and
      deltaF(LCC) components. In myocytes from failing hearts, stimulation of PKA
      failed to induce a shift in Ca2+ release voltage dependence toward more positive
      membrane potentials. Although the total and NCX-mediated Ca2+ entries were
      increased again, deltaF(Tot) did not significantly exceed the sum of deltaF(LCC)
      and deltaF(NCX). We conclude that the LCC and NCX Ca2+-entry pathways interact
      synergistically to trigger SR Ca2+ release on depolarization to positive membrane
      potentials in PKA-stimulated cardiac muscle. In heart failure, this new form of
      Ca2+ release is diminished and may potentially account for the compromised
      contractile performance and reduced functional reserve in failing hearts.

PMID- 15975979
TI  - Effects of calcineurin activation on insulin-, AICAR- and contraction-induced
      glucose transport in skeletal muscle.
AB  - Skeletal muscle is composed of fast- and slow-twitch fibres with distinctive
      physiological and metabolic properties. The calmodulin-activated serine/threonine
      protein phosphatase calcineurin activates fast- to slow-twitch skeletal muscle
      remodelling through the induction of the slow-twitch skeletal muscle fibre gene
      expression programme, thereby enhancing insulin-stimulated glucose uptake and
      offering protection against dietary-induced insulin resistance. Given the
      profound influence of skeletal muscle fibre type on insulin-mediated responses,
      we determined whether the fast- to slow-twitch fibre-type transformation leads to
      alterations in insulin-independent glucose uptake in transgenic mice expressing a
      constitutively active form of calcineurin (MCK-CnA* mice). We determined whether
      skeletal muscle remodelling by activated calcineurin alters glucose transport in
      response to the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4
      carboxamide-beta-D-ribofuranoside (AICAR) or muscle contraction, two divergent
      insulin-independent activators of glucose transport. While insulin-stimulated
      glucose transport was increased 52%, the AICAR effect on glucose transport was
      27% lower in MCK-CnA* mice versus wild-type mice (P < 0.05). In contrast, glucose
      transport was similar between genotypes after in vitro muscle contraction. Fibre
      type transformation was associated with increased AMPKgamma1, decreased
      AMPKgamma3 and unchanged AMPKgamma2 protein expression between MCK-CnA* and wild
      type mice (P < 0.05). The loss of AICAR-mediated glucose uptake is coupled to
      changes in the AMPK isoform expression, suggesting fibre-type dependence of the
      AICAR responses on glucose uptake. In conclusion, improvements in skeletal muscle
      glucose transport in response to calcineurin-induced muscle remodelling are
      limited to insulin action.

PMID- 15975980
TI  - Stimulation-induced changes in lower limb corticomotor excitability during
      treadmill walking in humans.
AB  - Magnetic stimulation of human primary motor cortex (M1) paired with electrical
      stimulation of a peripheral motor nerve has been used to produce a lasting
      modulation of corticomotor (CM) excitability. This 'paired associative
      stimulation' (PAS) protocol has been used to induce bidirectional changes in
      excitability in upper limb CM pathways. The present study tested the hypothesis
      that temporally dependent PAS applied to the common peroneal nerve during the
      swing phase of walking would induce bidirectional changes in CM excitability
      consistent with the Hebbian principle of activity-dependent plasticity. Fourteen
      subjects with no known neurological disorder participated in two data collection
      sessions each. PAS was delivered as a single block of 120 pairs of stimuli
      delivered in a 10 min period during treadmill walking at 4.0 km h(-1). Changes in
      CM excitability were assessed by examining the size of motor potentials evoked by
      transcranial magnetic stimulation prior to and following PAS. Tibialis anterior
      motor-evoked potentials amplitude increased to 121% over baseline when the
      magnetic stimulus was delivered over M1 after the estimated arrival time of the
      afferent volley in sensorimotor cortex and decreased to 83% of baseline when the
      magnetic stimulus was delivered prior to the estimated afferent volley arrival.
      This extent of modulation was undiminished following a further 10 min period of
      walking without stimulation. The temporal nature of the bidirectional effects
      following PAS, their rapid evolution and subsequent persistence supported the
      study's hypothesis and were similar to the effects described by others in
      quiescent muscles of the upper limb.

PMID- 15975981
TI  - Endothermic force generation, temperature-jump experiments and effects of
      increased [MgADP] in rabbit psoas muscle fibres.
AB  - We studied, by experiment and by kinetic modelling, the characteristics of the
      force increase on heating (endothermic force) in muscle. Experiments were done on
      maximally Ca2+-activated, permeabilized, single fibres (length approximately 2
      mm; sarcomere length, 2.5 microm) from rabbit psoas muscle; [MgATP] was 4.6 mM,
      pH 7.1 and ionic strength was 200 mM. A small-amplitude (approximately 3 degrees
      C) rapid laser temperature-jump (0.2 ms T-jump) at 8-9 degrees C induced a
      tension rise to a new steady state and it consisted of two (fast and slow)
      exponential components. The T-jump-induced tension rise became slower as [MgADP]
      was increased, with half-maximal effect at 0.5 mM [MgADP]; the pre- and post-T
      jump tension increased approximately 20% with 4 mM added [MgADP]. As determined
      by the tension change to small, rapid length steps (<1.4%L0 complete in <0.5 ms),
      the increase of force by [MgADP] was not associated with a concomitant increase
      of stiffness; the quick tension recovery after length steps (Huxley-Simmons phase
      2) was slower with added MgADP. In steady-state experiments, the tension was
      larger at higher temperatures and the plot of tension versus reciprocal absolute
      temperature was sigmoidal, with a half-maximal tension at 10-12 degrees C; the
      relation with added 4 mM MgADP was shifted upwards on the tension axis and
      towards lower temperatures. The potentiation of tension with 4 mM added MgADP was
      20-25% at low temperatures (approximately 5-10 degrees C), but approximately 10%
      at the physiological temperatures (approximately 30 degrees C). The shortening
      velocity was decreased with increased [MgADP] at low and high temperatures. The
      sigmoidal relation between tension and reciprocal temperature, and the basic
      effects of increased [MgADP] on endothermic force, can be qualitatively simulated
      using a five-step kinetic scheme for the crossbridge/A-MATPase cycle where the
      force generating conformational change occurs in a reversible step before the
      release of inorganic phosphate (P(i)), it is temperature sensitive (Q10 of
      approximately 4) and the release of MgADP occurs by a subsequent, slower, two
      step mechanism. Modelling shows that the sigmoidal relation between force and
      reciprocal temperature arises from conversion of preforce-generating (A
      M.ADP.P(i)) states to force-bearing (A-M.ADP) states as the temperature is
      raised. A tension response to a simulated T-jump consists of three (one fast and
      two slow) components, but, by combining the two slow components, they could be
      reduced to two; their relative amplitudes vary with temperature. The model can
      qualitatively simulate features of the tension responses induced by large-T-jumps
      from low starting temperatures, and those induced by small-T-jumps from different
      starting temperatures and, also, the interactive effects of P(i) and temperature
      on force in muscle fibres.

PMID- 15975982
TI  - Fetal cardiovascular, metabolic and endocrine responses to acute hypoxaemia
      during and following maternal treatment with dexamethasone in sheep.
AB  - In sheep, direct fetal treatment with dexamethasone alters basal cardiovascular
      function and the cardiovascular response to acute hypoxaemia. However, in human
      clinical practice, dexamethasone is administered to the mother, not to the fetus.
      Hence, this study investigated physiological responses to acute hypoxaemia in
      fetal sheep during and following maternal treatment with dexamethasone in doses
      and at dose intervals used in human clinical practice. Under anaesthesia, 18
      fetal sheep were instrumented with vascular and amniotic catheters, a carotid
      flow probe and a femoral flow probe at 118 days gestation (term ca 145 days).
      Following 6 days recovery at 124 days gestation, 10 ewes received dexamethasone
      (2 x 12 mg daily i.m. injections in saline). The remaining animals were saline
      injected as age-matched controls. Two episodes of hypoxaemia (H) were induced in
      all animals by reducing the maternal F(IO2)for 1 h (H1, 8 h after the second
      injection; H2, 3 days after the second injection). In fetuses whose mothers
      received saline, hypoxaemia induced significant increases in fetal arterial blood
      pressure, carotid blood flow and carotid vascular conductance and femoral
      vascular resistance, significant falls in femoral blood flow and femoral vascular
      conductance and transient bradycardia. These cardiovascular responses were
      accompanied by a fall in arterial pH, increases in blood glucose and blood
      lactate concentrations and increased plasma concentrations of catecholamines. In
      fetuses whose mothers were treated with dexamethasone, bradycardia persisted
      throughout hypoxaemia, the magnitude of the femoral vasoconstriction, the
      glycaemic, lactacidaemic and acidaemic responses and the plasma concentration of
      neuropeptide Y (NPY) were all enhanced during H1. However, during H2, all of
      these physiological responses were similar to saline controls. In dexamethasone
      fetuses, the increase in plasma adrenaline was attenuated during H1 and the
      increase in carotid vascular conductance during hypoxaemia failed to reach
      statistical significance both during H1 and during H2. These data show that
      maternal treatment with dexamethasone in doses and intervals used in human
      obstetric practice modified the fetal cardiovascular, metabolic and endocrine
      defence responses to acute hypoxaemia. Furthermore, dexamethasone-induced
      alterations to these defences depended on whether the hypoxaemic challenge
      occurred during or following maternal dexamethasone treatment.

PMID- 15975983
TI  - Colour helps to solve the binocular matching problem.
AB  - The spatial differences between the two retinal images, called binocular
      disparities, can be used to recover the three-dimensional (3D) aspects of a
      scene. The computation of disparity depends upon the correct identification of
      corresponding features in the two images. Understanding what image features are
      used by the brain to solve this binocular matching problem is an important issue
      in research on stereoscopic vision. The role of colour in binocular vision is
      controversial and it has been argued that colour is ineffective in achieving
      binocular vision. In the current experiment subjects were required to indicate
      the amount of perceived depth. The stimulus consisted of an array of fronto
      parallel bars uniformly distributed in a constant sized volume. We studied the
      perceived depth in those 3D stimuli by manipulating both colour (monochrome,
      trichrome) and luminance (congruent, incongruent). Our results demonstrate that
      the amount of perceived depth was influenced by colour, indicating that the
      visual system uses colour to achieve binocular matching. Physiological data have
      revealed cortical cells in macaque V2 that are tuned both to binocular disparity
      and to colour. We suggest that one of the functional roles of these cells may be
      to help solve the binocular matching problem.

PMID- 15975984
TI  - Molecular mapping of a site for Cd2+-induced modification of human ether-a-go-go
      related gene (hERG) channel activation.
AB  - Cd(2+) slows the rate of activation, accelerates the rate of deactivation and
      shifts the half-points of voltage-dependent activation (V(0.5,act)) and
      inactivation (V(0.5,inact)) of human ether-a-go-go-related gene (hERG) K(+)
      channels. To identify specific Cd(2+)-binding sites on the hERG channel, we
      mutated potential Cd(2+)-coordination residues located in the transmembrane
      domains or extracellular loops linking these domains, including five Cys, three
      His, nine Asp and eight Glu residues. Each residue was individually substituted
      with Ala and the resulting mutant channels heterologously expressed in Xenopus
      oocytes and their biophysical properties determined with standard two
      microelectrode voltage-clamp technique. Cd(2+) at 0.5 mM caused a +36 mV shift of
      V(0.5,act) and a +18 mV shift of V(0.5,inact) in wild-type channels. Most mutant
      channels had a similar sensitivity to 0.5 mM Cd(2+). Mutation of single Asp
      residues located in the S2 (D456, D460) or S3 (D509) domains reduced the Cd(2+)
      induced shift in V(0.5,act), but not V(0.5,inact). Combined mutations of two or
      three of these key Asp residues nearly eliminated the shift induced by 0.5 mM
      Cd(2+). Mutation of D456, D460 and D509 also reduced the comparatively low
      affinity effects of Ca(2+) and Mg(2+) on V(0.5,act). Extracellular Cd(2+)
      modulates hERG channel activation by binding to a coordination site formed, at
      least in part, by three Asp residues.

PMID- 15975985
TI  - Identification and properties of parietal pleural afferents in rabbits.
AB  - Although pain and dyspnoea are common symptoms in pleural diseases, there are few
      studies on the sensory innervation of the pleura. Using rabbits, after removal of
      all muscles in the intercostal space to be studied, we investigated the afferents
      of the internal intercostal nerve by applying to the internal thoracic wall
      pieces of gauze soaked in warmed (37 degrees C), buffered saline (mechanical
      stimulation) or solutions containing lactic acid, inflammatory mediators or
      capsaicin (chemical stimulation). The afferent conduction velocity ranged from
      0.5 to 14 m s(-1). Most units (97%) were activated by mechanical stimulation of
      the pleura (local positive pressure range = 4.5-8.5 cmH2O) and we found a linear
      relationship between the discharge rate of afferents and the force applied to the
      thoracic wall. The majority of mechanosensitive units (70%) also responded to one
      or several chemical agents. Thus, the afferents were activated by lactic acid
      (49%) and/or a mixture of inflammatory mediators (50%). Local application of
      capsaicin elicited an initial increased or decreased background afferent activity
      in 57% of the afferents, a delayed decrease in firing rate being noted in some
      units initially activated by capsaicin. Capsaicin blocked the afferent response
      to a further application of inflammatory mediators but did not affect the
      mechanosensitive units. Thus, sensory endings connected with thin myelinated and
      unmyelinated fibres in the internal intercostal nerve detect the mechanical and
      chemical events of pleural diseases.

PMID- 15975987
TI  - Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle
      group specific mechanisms in humans.
AB  - Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal
      muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and
      subunit specific mRNA are unknown. Ten healthy male subjects ingested
      dexamethasone for 5 days and the effects on Na+,K+ pump content, maximal activity
      and subunit specific mRNA level (alpha1, alpha2, beta1, beta2, beta3) in deltoid
      and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+
      pump activity, as well as alpha1, alpha2, beta1 and beta2 mRNA levels were higher
      (P < 0.05) in vastus lateralis than in deltoid. Dexamethasone treatment increased
      Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 +/- 7% (P <
      0.05) and 18 +/- 6% (P < 0.05) as well as Na+,K+ pump content by 18 +/- 9% (P <
      0.001) and 24 +/- 8% (P < 0.01), respectively. Treatment with dexamethasone
      resulted in a higher alpha1, alpha2, beta1 and beta2 mRNA expression in the
      deltoid (P < 0.05), but no effects on Na+,K+ pump mRNA were detected in vastus
      lateralis. In conclusion, dexamethasone treatment increased maximal Na+,K+ pump
      activity in both vastus lateralis and deltoid muscles. The relative importance of
      transcription and translation in the glucocorticoid-induced regulation of Na+,K+
      pump expression seems to be muscle specific and possibly dependent on the actual
      training condition of the muscle, such that a high Na+,K+ pump maximal activity
      and mRNA level prior to treatment prevents the transcriptional response to
      dexamethasone, but not the increase in Na+,K+ pump content and maximal activity.

PMID- 15975988
TI  - Grasping the role of technology: a conversation with Ron Dollens. Interview by
      John K. Iglehart.
AB  - In an interview with Health Affairs founding editor John Iglehart, Ron Dollens
      outlines the differences between drug and device companies in the current U.S.
      health care marketplace. He discusses at length the recent Medicare coverage
      decision regarding implantable cardiac defibrillators, one of his company's major
      innovations. He sees a growing trend for cost-effectiveness to be considered
      along with a device's safety and efficacy, and he finds this to be appropriate in
      an environment characterized by constrained resources. He believes that the
      United States must find a solution to the problem of uninsurance, if our health
      care system is to remain competitive in a global economy.

PMID- 15975986
TI  - Cell shrinkage as a signal to apoptosis in NIH 3T3 fibroblasts.
AB  - Cell shrinkage is a hallmark of the apoptotic mode of programmed cell death, but
      it is as yet unclear whether a reduction in cell volume is a primary activation
      signal of apoptosis. Here we studied the effect of an acute elevation of
      osmolarity (NaCl or sucrose additions, final osmolarity 687 mosmol l(-1)) on NIH
      3T3 fibroblasts to identify components involved in the signal transduction from
      shrinkage to apoptosis. After 1.5 h the activity of caspase-3 started to increase
      followed after 3 h by the appearance of many apoptotic-like bodies. The caspase-3
      activity increase was greatly enhanced in cells expressing a constitutively
      active G protein, Rac (RacV12A3 cell), indicating that Rac acts upstream to
      caspase-3 activation. The stress-activated protein kinase, p38, was significantly
      activated by phosphorylation within 30 min after induction of osmotic shrinkage,
      the phosphorylation being accelerated in fibroblasts overexpressing Rac.
      Conversely, the activation of the extracellular signal-regulated kinase (Erk1/2)
      was initially significantly decreased. Subsequent to activation of p38, p53 was
      activated through serine-15 phosphorylation, and active p53 was translocated from
      the cytosol to the nucleus. Inhibition of p38 in Rac cells reduced the activation
      of both p53 and caspase-3. After 60 min in hypertonic medium the rate constants
      for K+ and taurine efflux were increased, particular in Rac cells. We suggest the
      following sequence of events in the cell shrinkage-induced apoptotic response:
      cellular shrinkage activates Rac, with activation of p38, followed by
      phosphorylation and nuclear translocation of p53, resulting in permeability
      increases and caspase-3 activation.

PMID- 15975989
TI  - How changes in the Medicare coverage process have facilitated the spread of new
      technologies.
AB  - The Medicare coverage decision process can affect the availability and use of new
      technologies. The Centers for Medicare and Medicaid Services (CMS) has recently
      made advances in making its coverage decision process speedier, predictable, and
      more transparent. The CMS recently issued draft Coverage with Evidence
      Development (CED) guidance to assure that Medicare beneficiaries have access to
      new technologies through expanded coverage criteria, while gathering information
      that can be helpful to the doctors who care for them. The CMS continues these
      efforts with the goal of improving the evidence used for high-quality care, while
      avoiding unnecessary risks and costs.

PMID- 15975990
TI  - Prevention of restenosis by a novel drug-eluting stent system with a dose
      adjustable, polymer-free, on-site stent coating.
AB  - AIMS: Drug-eluting stents (DES) represent a major advance in interventional
      cardiology. Along with the success shown, current DES also present limitations
      related to the presence of polymer-coating, fixed drug, and dose used. With the
      ISAR (Individualized Drug-Eluting Stent System to Abrogate Restenosis) project, a
      DES system has been developed that permits individualized choice of the drug and
      dose to use for the given patient. The objective of this prospective dose finding
      study was to assess the feasibility, safety, and efficacy of a polymer-free on
      site stent coating with increasing rapamycin doses. METHODS AND RESULTS: In this
      dose finding study, 602 patients were sequentially enrolled in four groups:
      microporous bare metal stent (BMS), DES stents coated with a 0.5, 1.0, and 2.0%
      rapamycin solution. The angiographic in-segment restenosis rate at follow-up
      angiography was the primary study endpoint. In-segment restenosis was
      significantly reduced from 25.9% with BMS to 18.9, 17.2, and 14.7% with 0.5, 1.0,
      and 2.0% rapamycin-eluting stents, respectively (P=0.024). Similarly, the need
      for target lesion revascularization at 1 year follow-up was reduced from 21.5%
      with BMS to 16.4, 12.6, and 8.8% with 0.5, 1.0, and 2.0% rapamycin-eluting
      stents, respectively (P=0.006). CONCLUSION: The placement of polymer-free stents
      coated on-site with rapamycin is feasible and safe. Furthermore, a dose-dependent
      efficacy in restenosis prevention is achievable with this new DES concept.

PMID- 15975991
TI  - 13-year follow-up of the German angioplasty bypass surgery investigation.
AB  - AIMS: The German Angioplasty Bypass Surgery Investigation was designed to compare
      symptomatic efficacy and safety of percutaneous coronary balloon angioplasty
      (PTCA) with coronary artery bypass surgery (CABG) in patients with symptomatic
      multi-vessel disease. This follow-up study was performed to determine the long
      term outcome of patients following these interventions. METHODS AND RESULTS: From
      1986 to 1991, 359 patients with angina CCS class II-IV, age below 75 years, and
      coronary multi-vessel disease requiring revascularization of at least two major
      coronary vessels were recruited at eight German centres and randomized to PTCA or
      CABG. From 337 patients undergoing the planned procedure, 324 patients could be
      followed-up (96%). Baseline parameters were identical in both groups, 2.2+/-0.6
      vessels were treated in CABG patients, whereas 1.9+/-0.5 vessels were treated in
      PTCA patients. Thirty-seven per cent of surgical patients received internal
      mammary artery grafts, while no stents were used in patients undergoing PTCA. At
      the end of the 13-year follow-up period, the degree of angina, the degree of
      dyspnea, and the utilization of nitrates were comparable in both groups. With a
      total number of 76 deaths, Kaplan-Meier analysis revealed a comparable
      distribution in both groups. Although time to first re-intervention was
      significantly shorter in the PTCA group, P<0.001, frequencies of re-intervention
      (CABG, n=94; PTCA, n=136) and crossover rates (CABG to PTCA, n=49; PTCA to CABG,
      n=51) were comparable in both groups. CONCLUSION: The results of our 13-year
      follow-up suggest that in patients with symptomatic multi-vessel disease, both
      PTCA and CABG are associated with a comparable long-term survival and symptomatic
      efficacy. How far these results may be altered by developments such as drug
      eluting stents or off-pump surgery remains to be determined.

PMID- 15975992
TI  - Cardiology and nephrology: time for a more integrated approach to patient care?

PMID- 15975993
TI  - Inflammation in the genesis and perpetuation of atrial fibrillation.
AB  - The prevalence and persistence of atrial fibrillation (AF) and the relative
      inefficacy of the currently available pharmacotherapy requires development of new
      treatment strategies. Recent findings have suggested a mechanistic link between
      inflammatory processes and the development of AF. Epidemiological studies have
      shown an association between C-reactive protein and both the presence of AF and
      the risk of developing future AF. In case-control studies, C-reactive protein is
      significantly elevated in AF patients and is associated with successful
      cardioversion. Moreover, C-reactive protein elevation is more pronounced in
      patients with persistent AF than in those with paroxysmal AF. Furthermore,
      treatment with glucocorticoids, statins, angiotensin converting enzyme
      inhibitors, and angiotensin II receptor blockers seems to reduce recurrence of
      AF. Part of this anti-arrhythmic effect may be through anti-inflammatory
      activity. This article reviews what is known about inflammation in genesis and
      perpetuation of AF, the putative underlying mechanisms, and possible therapeutic
      implications for the inhibition of inflammation as an evolving treatment modality
      for AF.

PMID- 15975994
TI  - Angiotensin-converting enzyme inhibition in diabetic nephropathy: it's all the
      RAGE.

PMID- 15975995
TI  - Roles of insulin receptor substrates in insulin-induced stimulation of renal
      proximal bicarbonate absorption.
AB  - Insulin resistance is frequently associated with hypertension, but the mechanism
      underlying this association remains speculative. Although insulin is known to
      modify renal tubular functions, little is known about roles of insulin receptor
      substrates (IRS) in the renal insulin actions. For clarifying these issues, the
      effects of insulin on the rate of bicarbonate absorption (JHCO3-) were compared
      in isolated renal proximal tubules from wild-type, IRS1-deficient (IRS1-/-), and
      IRS2-deficient (IRS2-/-) mice. In wild-type mice, physiologic concentrations of
      insulin significantly increased JHCO3-. This stimulation was completely inhibited
      by wortmannin and LY-294002, indicating that the phosphatidylinositol 3-kinase
      pathway mediates the insulin action. The stimulatory effect of insulin on JHCO3-
      was completely preserved in IRS1-/- mice but was significantly attenuated in IRS2
      /- mice. Similarly, insulin-induced Akt phosphorylation was preserved in IRS1-/-
      mice but was markedly attenuated in IRS2-/- mice. Furthermore, insulin-induced
      tyrosine phosphorylation of IRS2 was more prominent than that of IRS1. These
      results indicate that IRS2 plays a major role in the stimulation of renal
      proximal absorption by insulin. Because defects at the level of IRS1 may underlie
      at least some forms of insulin resistance, sodium retention, facilitated by
      hyperinsulinemia through the IRS1-independent pathway, could be an important
      factor in pathogenesis of hypertension in insulin resistance.

PMID- 15975996
TI  - Prevalence, severity, and importance of physical and emotional symptoms in
      chronic hemodialysis patients.
AB  - The prevalence, severity, and clinical significance of physical and emotional
      symptoms in patients who are on maintenance hemodialysis remain incompletely
      characterized. This study sought to assess symptoms and their relationship to
      quality of life and depression. The recently developed Dialysis Symptom Index was
      used to assess the presence and the severity of 30 symptoms. The Illness Effects
      Questionnaire and Beck Depression Inventory were used to evaluate quality of life
      and depression, respectively. Correlations among symptom burden, symptom
      severity, quality of life, and depression were assessed using Spearman
      correlation coefficient. A total of 162 patients from three dialysis units were
      enrolled. Mean age was 62 y, 48% were black, 62% were men, and 48% had diabetes.
      The median number of symptoms was 9.0 (interquartile range 6 to 13). Dry skin,
      fatigue, itching, and bone/joint pain each were reported by > or =50% of
      patients. Seven additional symptoms were reported by >33% of patients. Sixteen
      individual symptoms were described as being more than "somewhat bothersome."
      Overall symptom burden and severity each were correlated directly with impaired
      quality of life and depression. In multivariable analyses adjusting for
      demographic and clinical variables including depression, associations between
      symptoms and quality of life remained robust. Physical and emotional symptoms are
      prevalent, can be severe, and are correlated directly with impaired quality of
      life and depression in maintenance hemodialysis patients. Incorporating a
      standard assessment of symptoms into the care provided to maintenance
      hemodialysis patients may provide a means to improve quality of life in this
      patient population.

PMID- 15975997
TI  - Aldosterone stimulates proliferation of mesangial cells by activating mitogen
      activated protein kinase 1/2, cyclin D1, and cyclin A.
AB  - Recently, attention has been focused on the role of aldosterone in the
      pathophysiology of hypertension and cardiovascular disease. Several clinical and
      experimental data support the hypothesis that aldosterone contributes to the
      progression of renal injury. However, the molecular mechanisms of the effects of
      aldosterone in signal transduction and the cell-cycle progression of mesangial
      cells are not well known. For determining the signaling pathway of aldosterone in
      cultured mesangial cells, the effects of aldosterone on the mitogen-activated
      protein kinase 1/2 (MAPK1/2) pathway and the promoter activities of cyclin D1,
      cyclin A, and cyclin E were investigated. First, it was shown that the
      mineralocorticoid receptor (MR) was expressed in rat mesangial cells and
      glomeruli and that aldosterone stimulated the proliferation of mesangial cells
      via the MR and MAPK1/2 pathway. Next, it was demonstrated that aldosterone
      stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.
      Aldosterone induced cyclin D1 and cyclin A promoter activities and protein
      expressions, as well as the increments of CDK2 and CDK4 kinase activities. The
      presence of CYP11B2 and 11beta-HSD2 mRNA in rat mesangial cells also was shown.
      In conclusion, aldosterone seems to exert mainly MR-induced effects that
      stimulate c-Raf, MEK1/2, MAPK1/2, the activities of CDK2 and CDK4, and the cell
      cycle progression in mesangial cells. MR antagonists may serve as a potential
      therapeutic approach to mesangial proliferative disease.

PMID- 15975998
TI  - Protein-leaking membranes for hemodialysis: a new class of membranes in search of
      an application?
AB  - A new class of membranes that leak protein has been developed for hemodialysis.
      These membranes provide greater clearances of low molecular weight proteins and
      small protein-bound solutes than do conventional high-flux dialysis membranes but
      at the cost of some albumin loss into the dialysate. Protein-leaking membranes
      have been used in a small number of clinical trials. The results of these trials
      suggest that protein-leaking membranes improve anemia correction, decrease plasma
      total homocysteine concentrations, and reduce plasma concentrations of
      glycosylated and oxidized proteins. However, it is not clear yet that routine use
      of protein-leaking membranes is warranted. Specific uremic toxins that are
      removed by protein-leaking membranes but not conventional high-flux membranes
      have not been identified. It is also unclear whether protein-leaking membranes
      offer benefits beyond those obtained with conventional high-flux membranes used
      in convective therapies, such as hemofiltration and hemodiafiltration. Finally,
      the amount of albumin loss that can be tolerated by hemodialysis patients in a
      long-term therapy has yet to be determined. Protein-leaking membranes offer a new
      approach to improving outcomes in hemodialysis, but whether their benefits will
      outweigh their disadvantages will require more basic and clinical research.

PMID- 15975999
TI  - NF-kappaB regulates Fas-mediated apoptosis in HIV-associated nephropathy.
AB  - Renal parenchymal injury in HIV-associated nephropathy (HIVAN) is characterized
      by epithelial proliferation, dedifferentiation, and apoptosis along the entire
      length of the nephron. Although apoptotic cell death in HIVAN has been well
      documented, the mechanism for HIV-induced apoptosis is poorly understood. Whether
      the epithelial apoptosis in HIVAN is mediated by NF-kappaB-activated Fas ligand
      expression was investigated here. In human HIVAN and HIV-1 transgenic mouse
      kidney specimens, the expression of Fas receptor and ligand proteins were
      markedly upregulated on epithelium in diseased glomerular and tubulointerstitial
      compartments when compared with normal. Podocyte cell lines that were derived
      from HIV-1 transgenic mice showed a similar upregulation of Fas receptor
      expression and de novo expression of Fas ligand by semiquantitative reverse
      transcription-PCR and Western blotting. In cultured podocytes, cross-linking of
      the Fas receptor to mimic ligand binding induced caspase 8 activity and apoptosis
      in both normal and HIVAN podocytes. Because constitutive NF-kappaB activity has
      been demonstrated in HIVAN epithelia, evidence for transcriptional control of the
      Fas ligand expression by NF-kappaB was sought. With the use of cultured
      podocytes, expression of a Fas ligand promoter reporter plasmid was higher in
      HIVAN podocytes, indicating increased transcriptional activity. In addition,
      chromatin immunoprecipitation assays were performed to demonstrate that p65
      containing (RelA) complexes bound the Fas ligand promoter and that suppression of
      activated NF-kappaB with a peptide inhibitor could reduce the expression of Fas
      ligand mRNA in HIVAN podocytes. These results suggest that NF-kappaB may regulate
      Fas-mediated apoptosis in HIVAN by controlling the expression of Fas ligand in
      renal epithelium.

PMID- 15976000
TI  - Contribution of cubilin and amnionless to processing and membrane targeting of
      cubilin-amnionless complex.
AB  - Cubilin is a peripheral apical membrane receptor for multiple ligands that are
      taken up in several absorptive epithelia. Recently, amnionless (AMN) was
      identified to form a functional receptor complex with cubilin. By expression in
      transfected polarized MDCK cells of AMN and several cubilin fragments, including
      a functional "mini" version of cubilin, the processing, sorting, and membrane
      anchoring of the complex to the apical membrane were investigated. The results
      show that truncation mutants, including the N-terminal domain of cubilin, did not
      appear at the plasma membrane but instead were retained in the endoplasmic
      reticulum or partially secreted into the medium. Coexpression with AMN led to
      efficient transport to the apical cell surface of the cubilin constructs, which
      included the EGF domains, and prevented release into the medium. AMN co
      precipitated with cubilin and co-localized with cubilin at the apical cell
      surface. Apical sorting was observed for a broad set of nonoverlapping cubilin
      fragments without the N-terminal region, in the absence of AMN. The preference
      for apical sorting disappeared when glycosylation was inhibited by tunicamycin.
      In conclusion, it is shown that both units contribute to the processing of the
      cubilin-AMN complex to the apical membrane: AMN interacts with the EGF domains of
      cubilin and is responsible for membrane attachment and export of the complex from
      the endoplasmic reticulum, whereas the extracellular cubilin molecule is
      responsible for apical sorting of the complex in a carbohydrate-dependent manner.

PMID- 15976001
TI  - Coagulation cascade activation causes CC chemokine receptor-2 gene expression and
      mononuclear cell activation in hemodialysis patients.
AB  - Priming of the coagulation cascade during hemodialysis (HD) leads to the release
      of activated factor X (FXa). The binding of FXa to its specific receptors,
      effector protease receptor-1 (EPR-1) and protease-activated receptor-2 (PAR-2),
      may induce the activation of peripheral blood mononuclear cells (PBMC) and
      promote a chronic inflammatory state that is responsible for several HD-related
      morbidities. In the attempt to elucidate the mechanisms underlying the
      coagulation-associated inflammation in HD, 10 HD patients were randomized to be
      treated subsequently with a cellulose acetate membrane (CA) and Ethylen-vinyl
      alcohol (EVAL), a synthetic membrane that has been shown to reduce FXa
      generation. At the end of each experimental period, surface FXa and thrombin
      receptors (EPR-1 and PAR-1, -2, and -4) and CCR2 (monocyte chemoattractant
      protein-1 receptor) gene expression in isolated PBMC were examined. the ability
      of dialytic membranes to activate protein-tyrosine kinases and the stress
      activated kinase JNK and to modulate the generation of terminal complement
      complex (TCC) was also investigated. EPR-1 and PAR-2 and -4 mRNA expression,
      barely detectable in normal PBMC, were significantly upregulated in HD patients,
      particularly in those who were treated with CA. A striking increase of tyrosine
      phosphorylated proteins and JNK activation was observed at the end of HD only in
      CA-treated patients. Simultaneously, an increased gene expression for both
      splicing isoforms of CCR2, A and B, only in PBMC from CA-treated patients was
      demonstrated. The increased CCR-2 mRNA abundance was followed by a significant
      increase in its protein synthesis. The high expression of CCR2 was associated
      with an increased generation of plasma TCC and a significant drop in leukocyte
      and monocyte count. By contrast, EVAL treatment slightly lowered TCC generation
      and normalized leukocyte count. In vitro FXa induced CCR2 A and B expression and
      JNK activation in freshly isolated PBMC. FXa-induced CCR2 mRNA expression was
      completely abolished by JNK and tyrosine kinase inhibition. In conclusion, these
      data suggest that subclinical clotting activation may cause an increased CCR2
      gene and protein expression on uremic PBMC, contributing to HD-related chronic
      microinflammation. The use of the less coagulation-activating membrane, EVAL, may
      reduce PBMC activation through the modulation of the stress-activated kinase JNK.

PMID- 15976002
TI  - Intraperitoneal administration of recombinant receptor-associated protein causes
      phosphaturia via an alteration in subcellular distribution of the renal sodium
      phosphate co-transporter.
AB  - Megalin is a multifunctional endocytic receptor that is expressed in renal
      proximal tubules and plays critical roles in the renal uptake of various
      proteins. It was hypothesized that megalin-dependent endocytosis might play a
      role in renal phosphate reabsorption. For addressing the short-term effects of
      altered megalin function, a recombinant protein for the soluble form of 39-kD
      receptor-associated protein (RAP) was administered intraperitoneally to 7-wk-old
      mice. Histidine (His)-tagged soluble RAP (amino acids 39 to 356) lacking the
      amino-terminal signal peptide and the carboxy-terminal endoplasmic reticulum
      retention signal was prepared by bacterial expression (designated His-sRAP).
      After the direct interaction between His-sRAP and megalin was confirmed, mice
      were given a single intraperitoneal administration of His-sRAP (3.5 mg/dose).
      Immunostaining and Western blot analyses demonstrated the uptake of His-sRAP and
      the accelerated internalization of megalin in proximal tubular cells 1 h after
      administration. In addition, internalization of the type II sodium/phosphate co
      transporter (NaPi-II) was observed. The effects of three sequential
      administrations of His-sRAP (3.5 mg/dose, three doses at 4-h intervals) then were
      examined, and increased urinary excretion of low molecular weight proteins,
      including vitamin D-binding protein, was found, which is consistent with findings
      reported for megalin-deficient mice. It is interesting that urinary excretion of
      phosphate was also increased, and the protein level of NaPi-II in the brush
      border membrane was decreased. Serum concentration of 25-hydroxyvitamin D was
      decreased, whereas the plasma level of intact parathyroid hormone was not altered
      by the administration of His-sRAP. The results suggest that the His-sRAP-induced
      acceleration of megalin-mediated endocytosis caused phosphaturia via altered
      subcellular distribution of NaPi-II.

PMID- 15976003
TI  - Dominant role of prostaglandin E2 EP4 receptor in furosemide-induced salt-losing
      tubulopathy: a model for hyperprostaglandin E syndrome/antenatal Bartter
      syndrome.
AB  - Increased formation of prostaglandin E2 (PGE2) is a key part of
      hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal
      disease characterized by NaCl wasting, water loss, and hyperreninism. Inhibition
      of PGE2 formation by cyclo-oxygenase inhibitors significantly lowers patient
      mortality and morbidity. However, the pathogenic role of PGE2 in HPS/aBS awaits
      clarification. Chronic blockade of the Na-K-2Cl co-transporter NKCC2 by diuretics
      causes symptoms similar to HPS/aBS and provides a useful animal model. In wild
      type (WT) mice and in mice lacking distinct PGE2 receptors (EP1-/-, EP2-/-, EP3-/
      , and EP4-/-), the effect of chronic furosemide administration (7 d) on urine
      output, sodium and potassium excretion, and renin secretion was determined.
      Furthermore, furosemide-induced diuresis and renin activity were analyzed in mice
      with defective PGI2 receptors (IP-/-). In all animals studied, furosemide
      stimulated a rise in diuresis and electrolyte excretion. However, this effect was
      blunted in EP1-/-, EP3-/-, and EP4-/- mice. Compared with WT mice, no difference
      was observed in EP2-/- and IP-/- mice. The furosemide-induced increase in plasma
      renin concentration was significantly decreased in EP4-/- mice and to a lesser
      degree also in IP-/- mice. Pharmacologic inhibition of EP4 receptors in
      furosemide-treated WT mice with the specific antagonist ONO-AE3-208 mimicked the
      changes in renin mRNA expression, plasma renin concentration, diuresis, and
      sodium excretion seen in EP4-/- mice. The GFR in EP4-/- mice was not changed
      compared with that in WT mice, which indicated that blunted diuresis and salt
      loss seen in EP4-/- mice were not a consequence of lower GFR. In summary, these
      findings demonstrate that the EP4 receptor mediates PGE2-induced renin secretion
      and that EP1, EP3, and EP4 receptors all contribute to enhanced PGE2-mediated
      salt and water excretion in the HPS/aBS model.

PMID- 15976004
TI  - Molecular analysis of a congenital iodide transport defect: G543E impairs
      maturation and trafficking of the Na+/I- symporter.
AB  - The Na+/I- symporter (NIS) is a key membrane glycoprotein that mediates active I-
      transport in the thyroid and other tissues. Upon isolation of the cDNA encoding
      NIS, 10 NIS mutations that cause congenital iodide transport defect have been
      identified. Three of these mutations (T354P, G395R, and Q267E) have been
      thoroughly characterized at the molecular level. All three NIS mutant proteins
      are correctly targeted to the plasma membrane; however, whereas Q267E displays
      minimal activity, T354P and G395R are inactive. Here, we show that in contrast to
      these mutants, G543E NIS matures only partially and is retained intracellularly;
      thus, it is not targeted properly to the cell surface, apparently because of
      faulty folding. These findings indicate that the G543 residue plays significant
      roles in NIS maturation and trafficking. Remarkably, NIS activity was rescued by
      small neutral amino acid substitutions (volume < 129 A3) at this position,
      suggesting that G543 is in a tightly packed region of NIS.

PMID- 15976005
TI  - Altered progesterone receptor isoform expression remodels progestin
      responsiveness of breast cancer cells.
AB  - The ovarian hormone progesterone is essential for normal breast development and
      function. However, it is also implicated in breast cancer development.
      Progesterone signals through two nuclear receptors [progesterone receptor A (PRA)
      and progesterone receptor B (PRB)], which display striking differences in
      transcriptional activity when analyzed separately. The two species are
      coexpressed equally in normal breast, but expression becomes markedly disrupted
      in breast cancer, where a predominance of PRA is common. To determine the impact
      on PR transcriptional activity of the shift from coexpression of PRA and PRB,
      observed in normal cells, to predominance of PRA, common in cancers, we modeled
      these changes in PR expression patterns using an inducible model of PRA
      predominance. At short treatment times progestin regulation was directed toward
      transcriptional modulators, whereas longer exposure more frequently targeted
      genes associated with regulation of cell shape, adhesion, and metabolism, and a
      number of these targets acquired responsiveness only when PRA predominance was
      achieved. Consistent with this, overexpression of PRA altered progestin effects
      on cell-substrate attachment and focal adhesion signaling. Our data suggest that
      disrupted balance of PRA and PRB remodels progestin responsiveness and that
      altered regulation of morphology and adhesion are important components of altered
      progestin response in breast cancer.

PMID- 15976006
TI  - Binding of estrogen receptor beta to estrogen response element in situ is
      independent of estradiol and impaired by its amino terminus.
AB  - The functions of 17beta-estradiol (E2) are mediated by estrogen receptor (ER)
      alpha and beta. ERs display similar DNA- and ligand-binding properties in vitro.
      However, ERbeta shows lower transcriptional activity than ERalpha from the
      estrogen response element (ERE)-dependent signaling. We predicted that distinct
      amino termini contribute to differences in transcription efficacies of ERs by
      affecting in situ ER-ERE interactions. We used chromatin immunoprecipitation and
      a novel in situ ERE competition assay, which is based on the ability of ER to
      compete for ERE binding with a designer activator that constitutively induces
      transcription from an ERE-driven reporter construct. Interference of activator
      mediated transcription by unliganded or liganded ERs was taken as an indication
      of ER-ERE interaction. Results revealed that ERs interacted with ERE similarly in
      the absence of E2. However, E2 enhanced the ERE binding of ERalpha but not that
      of ERbeta. The removal of the amino terminus increased the ERbeta-ERE interaction
      independent of E2. The ERbeta amino terminus also prevented E2-mediated
      enhancement of the chimeric ERalpha-ERE interaction. Thus, the amino terminus of
      ERbeta impairs the binding of ERbeta to ERE. The abrogation of ligand-dependent
      activation function 2 of the amino-terminally truncated ERbeta resulted in the
      manifestation of E2 effect on ERbeta-ERE interaction. This implies that E2
      mediated enhancement of ERbeta-ERE interaction is masked by the activation
      function 2, whereas the intact amino terminus is a dominant region that decreases
      the binding of ERbeta to ERE. Thus, ERbeta-ERE interaction is independent of E2
      and is impaired by its amino terminus. These findings provide an additional
      explanation for differences between ERalpha and ERbeta functions that could
      differentially affect the physiology and pathophysiology of E2 signaling.

PMID- 15976007
TI  - Gonadotropin-releasing hormone (GnRH) positively regulates corticotropin
      releasing hormone-binding protein expression via multiple intracellular signaling
      pathways and a multipartite GnRH response element in alphaT3-1 cells.
AB  - CRH-binding protein (CRH-BP) binds CRH with high affinity and inhibits CRH
      mediated ACTH release from anterior pituitary corticotrope-like cells in vitro.
      In female mouse pituitary, CRH-BP is localized not only in corticotropes, but is
      also expressed in gonadotropes and lactotropes. To investigate the functional
      significance of gonadotrope CRH-BP, we examined the molecular mechanisms
      underlying GnRH-regulated CRH-BP expression in alphaT3-1 gonadotrope-like cells.
      CRH-BP is endogenously expressed in alphaT3-1 cells, and quantitative real-time
      RT-PCR and ribonuclease protection assays demonstrate that GnRH induces a 3.7
      fold increase in CRH-BP mRNA levels. GnRH also induces intracellular CRH-BP (2.0
      fold) and secreted CRH-BP (5.3-fold) levels, as measured by [125I]CRH:CRH-BP
      chemical cross-linking. Transient transfection assays using CRH-BP promoter
      luciferase constructs indicate that GnRH regulation involves protein kinase C-,
      ERK- and calcium-dependent signaling pathways and is mediated via a multipartite
      GnRH response element that includes activator protein 1 and cAMP response element
      (CRE) sites. The CRE site significantly contributes to GnRH responsiveness,
      independent of protein kinase A, representing a unique form of multipartite GnRH
      regulation in alphaT3-1 cells. Furthermore, EMSAs indicate that alphaT3-1 nuclear
      proteins specifically bind at activator protein 1 and CRE sites. These data
      demonstrate novel regulation of pituitary CRH-BP, highlighting the importance of
      the pituitary gonadotrope as a potential interface between the stress and
      reproductive axes.

PMID- 15976008
TI  - Estrogen negatively regulates epidermal growth factor (EGF)-mediated signal
      transducer and activator of transcription 5 signaling in human EGF family
      receptor-overexpressing breast cancer cells.
AB  - Breast cancer cell growth may be stimulated by 17beta-estradiol (E2) or growth
      factors like epidermal growth factor (EGF). However, tumors typically depend on
      only one of these pathways and may overexpress either estrogen receptor (ER) or
      EGF receptor (EGFR) and related family members. Tumors overexpressing EGFR are
      more aggressive than those expressing ER. Intracellular mediators of these growth
      stimulatory pathways are not completely defined, but one potential common
      mediator of EGF and E2 signaling is the transcription factor signal transducer
      and activator of transcription 5 (STAT5). To investigate the role of STAT5 in
      potential crosstalk between E2 and EGF, MDA-MB231 and SKBr3 breast cancer cells,
      which are ER-negative and overexpress human EGF family receptors, were used.
      Introduction of ERalpha and treatment with E2 decreased EGF-induced tyrosine
      phosphorylation of STAT5b, basal and EGF-induced STAT5-mediated transcription,
      and EGF-stimulated DNA synthesis in these cells. Suppressive effects of E2
      EpsilonRalpha were specific for STAT5, as EGF stimulation of MAPK was unaffected.
      Deletion/mutation analysis of ERalpha demonstrated that the DNA-binding domain
      was insufficient, and that the ligand-binding domain was required for these
      responses. ERalpha transcriptional activity was not necessary for suppression of
      STAT5 activity. Overexpression of c-Src did not prevent suppression of STAT5
      activity by E2 and ERalpha. However, ERalpha did prevent basal increases in STAT5
      activity with overexpressed c-Src. In the context of human EGF receptor family
      overexpression, E2-ER opposes EGF signaling by regulating STAT5 activity. STAT5
      may be a crucial point of signaling for both E2 and growth factors in breast
      cancer cells, allowing targeted therapy for many types of breast tumors.

PMID- 15976009
TI  - PAC1 receptors mediate pituitary adenylate cyclase-activating polypeptide- and
      progesterone-facilitated receptivity in female rats.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) acts as a feed
      forward, paracrine/autocrine factor in the hypothalamic ventromedial nucleus
      (VMN) for receptivity and sensitizes pituitary hormone release for ovulation. The
      present study examined receptor(s) and signaling pathway by which PACAP enhances
      rodent lordosis. PACAP binds to PACAP (PAC1)- and vasoactive intestinal peptide
      preferring receptors (VPAC1, VPAC2). Ovariectomized rodents primed with estradiol
      (EB) were given PACAP or vasoactive intestinal peptide directly onto VMN cells.
      Only PACAP facilitated receptivity. Pretreatment with VPAC1 and VPAC2 inhibitors
      blocked both PACAP- and progesterone (P)-induced receptivity. Antisense (AS)
      oligonucleotides to PAC1 (not VPAC1 or VPAC2) inhibited the behavioral effect of
      PACAP and P. By real-time RT-PCR, EB, P and EB+P enhanced VMN mRNA expression of
      PAC1. Within the total PAC1 population, EB and EB+P induced expression of short
      form PAC1 and PAC1hop2 splice variants. Finally, blocking cAMP/protein kinase A
      signaling cascade by antagonists to cAMP activity and protein kinase A or by
      antisense to dopamine- and cAMP-regulated phosphoprotein of 32 kDa blocked the
      PACAP effect on behavior. Collectively, these findings provide evidence that
      progesterone receptor-dependent receptivity is, in part, dependent on PAC1
      receptors for intracellular VMN signaling and delineate a novel, steroid
      dependent mechanism for a feed-forward reinforcement of steroid receptor
      dependent reproductive receptivity.

PMID- 15976010
TI  - Large-scale modelling as a route to multiple surface comparisons of the CCP
      module family.
AB  - Numerous mammalian proteins are constructed from a limited repertoire of module
      types. Proteins belonging to the regulators of complement activation family-
      crucial for ensuring a complement-mediated immune response is targeted against
      infectious agents--are composed solely of complement control protein (CCP)
      modules. In the current study, CCP module sequences were grouped to allow
      selection of the most appropriate experimentally determined structures to serve
      as templates in an automated large-scale structure modelling procedure. The
      resulting 135 individual CCP module models, valuable in their own right, are
      available at the online database http://www.bru.ed.ac.uk/~dinesh/ccp-db.html.
      Comparisons of surface properties within a particular family of modules should be
      more informative than sequence alignments alone. A comparison of surface
      electrostatic features was undertaken for the first 28 CCP modules of complement
      receptor type 1 (CR1). Assignments to clusters based on surface properties differ
      from assignments to clusters based on sequences. This observation might reflect
      adaptive evolution of surface-exposed residues involved in protein-protein
      interactions. This illustrative example of a multiple surface-comparison was
      indeed able to pinpoint functional sites in CR1.

PMID- 15976011
TI  - A new yeast display vector permitting free scFv amino termini can augment ligand
      binding affinities.
AB  - Yeast surface display and sorting by flow cytometry are now widely used to direct
      the evolution of protein binding such as single-chain antibodies or scFvs. The
      available commercial yeast display vector pYD1 (Invitrogen) displays the protein
      of interest flanked on the N-terminus by Aga2, the disulfide of which binds the
      myristylated surface membrane protein Aga1. We have noted that two anti
      CD3epsilon scFvs expressed as fusion proteins suffer a 30- to 100-fold loss of
      affinity when placed NH(2) terminal to either truncated toxins or human serum
      albumin. In the course of affinity maturing one of these scFv (FN18) using pYD1
      we noted that the affinity towards the ectodomain of monkey CD3epsilongamma was
      too low to measure. Consequently we rebuilt pYD1 tethering the scFv off the NH(2)
      terminus of Aga2. This display vector, pYD5, now gave a positive signal
      displaying FN18 scFv with its ligand, monkey CD3epsilongamma. The apparent
      equilibrium association constant of the higher affinity scFv directed at human
      CD3epsilongamma increased approximately 3-fold when displayed on pYD5 compared
      with pYD1. These data show that for certain yeast-displayed scFvs a carboxy
      tethered scFv can result in increased ligand-scFv equilibrium association
      constants and thereby extend the low range of affinity maturation measurements.

PMID- 15976012
TI  - Long-term diagnostic stability and outcome in recent first-episode cohort studies
      of schizophrenia.
AB  - Knowing the long-term outcomes of schizophrenia and stability of a schizophrenia
      diagnosis are important from a clinical standpoint as well as essential to future
      research on diagnostic classifications and outcome. As in prior research on
      schizophrenia, prospectively designed long-term studies over the past 30 years
      find that the predominant course of illness includes chronically poor
      functioning, with little evidence of long-term improvement. Mortality due to
      suicide is significant at about 10% over 10-year periods of follow-up. Within
      studies, outcome domains are interrelated, and the relatively consistent
      predictors of poorer outcome include family history of schizophrenia, insidious
      onset, poor premorbid functioning, severity of negative symptoms, and severity
      and duration of untreated psychosis. Residing in a developed rather than a
      developing country is also associated with a poorer long-term course. The
      diagnostic stability of schizophrenia is less well studied. The positive
      predictive value exceeds 90%, and preliminary findings from the 10-year follow-up
      of the Suffolk County Mental Health Project cohort have found that the agreement
      across time increased from k = .52 (baseline to 10 years) to k = .76 (6 or 24
      months to 10 years). After discussing several limitations of the existing body of
      research, we suggest that future studies incorporate more "modifiable" risk
      factors into the assessment battery that could potentially be used as building
      blocks in experimental intervention designs.

PMID- 15976013
TI  - The environment and schizophrenia: the role of cannabis use.
AB  - Cannabis use is associated with poor outcome in existing schizophrenia and may
      precipitate psychosis in individuals with preexisting liability. To investigate
      the overall effect size and consistency of the association between cannabis and
      psychosis, a meta-analysis from prospective studies was carried out. The pooled
      odds ratio was 2.1 (95% CI: 1.7-2.5) and could not be explained by confounding or
      reverse causality. Evidence suggests that cannabis is a component cause in the
      development and prognosis of psychosis, in which mechanisms of gene-environment
      interaction are most likely to explain this association. Potential new methods to
      directly link genetic liability to the effects of cannabis are discussed.

PMID- 15976014
TI  - The histaminergic signaling system exerts a neuroprotective role against
      neurodegenerative-induced processes in the hamster.
AB  - The neurotoxic 3-nitropropionic acid (3-NP), a freckled milk vetch-derived
      inhibitor of mitochondrial enzymatic processes that is capable of mimicking the
      typical pathological features of neurodegenerative disorders, behaved in a
      differentiated manner in a hibernating rodent (hamster) with respect to a
      nonhibernating rodent (rat). Treatment of the two rodents with both an acute and
      chronic 3-NP dose supplied deleterious neuronal effects due to distinct histamine
      receptor (H(n)R) transcriptional activities, especially in the case of the rat.
      In hamsters, these treatment modalities accounted for overall reduced global
      activity in a freely moving environment and overt motor symptoms such as hindlimb
      dystonia and clasping with respect to the greater abnormal motor behaviors in
      rats. This behavioral difference appeared to be strongly related to qualitative
      fewer neuronal alterations and, namely, lesser crenated cell membranes, swollen
      mitochondria, and darkened nuclei in hamster brain areas. Moreover, a mixed
      H(1,3)R mRNA expression pattern was reported for both rodents treated with a
      chronic 3-NP dose as demonstrated by predominantly low H1R mRNA levels (>50%) in
      rat striatum and cortex, whereas extremely high H3R levels (>80%) characterized
      the lateral and central amygdala nuclei plus the striatum of hamsters.
      Interestingly, the H3R antagonist (thioperamide) blocked 3-NP-dependent behaviors
      plus induced an up-regulation of H1R levels in mainly the above-reported hamster
      amygdalar nuclei. Overall, these results show, for the first time, that a major
      protective role against neurodegenerative events appears to be strongly related
      to the expression activity of H(1,3)R subtypes of amygdalar neurons in this
      hibernating model.

PMID- 15976015
TI  - Inhibitory effects of 12-O-tetradecanoylphorbol-13-acetate alone or in
      combination with all-trans retinoic acid on the growth of cultured human pancreas
      cancer cells and pancreas tumor xenografts in immunodeficient mice.
AB  - Treatment of cultured PANC-1, MIA PaCa-2, and BxPC-3 human pancreatic
      adenocarcinoma cells with 0.1 to 1.6 nM 12-O-tetradecanoylphorbol-13-acetate
      (TPA) for 96 h inhibited the proliferation of these cells in a dose-dependent
      manner, and PANC-1 and MIA PaCa-2 cells were more sensitive to TPA than BxPC-3
      cells. Inhibition of proliferation by TPA in PANC-1 cells was associated with an
      increase in the level of p21, but this was not observed in MIA PaCa-2 or BxPC-3
      cells. The TPA-induced increase of p21 in PANC-1 cells was blocked by
      bisindolylmaleimide or rottlerin (inhibitors of protein kinase C). Studies in NCr
      immunodeficient mice with well established PANC-1 tumor xenografts indicated that
      daily i.p. injections of TPA strongly inhibited tumor growth, increased the
      percentage of caspase-3-positive cells, and decreased the ratio of mitotic cells
      to caspase-3-positive cells in the tumors. Studies with BxPC-3 tumors in NCr mice
      receiving daily i.p. injections of vehicle, TPA, all-trans retinoic acid (ATRA),
      or a TPA/ATRA combination showed that TPA had an inhibitory effect on tumor
      growth, but treatment of the animals with the TPA/ATRA combination had a greater
      inhibitory effect on tumor growth than TPA alone. Treatment with the TPA/ATRA
      combination resulted in a substantially decreased ratio of the percentage of
      mitotic cells to the percentage of caspase-3-positive cells in the tumors
      compared with tumors from the vehicle-treated control animals. The inhibitory
      effects of TPA on tumor growth occurred at clinically achievable blood levels.

PMID- 15976016
TI  - Radioligand binding properties and pharmacological characterization of 6-amino-N
      cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-298198), a
      high-affinity, selective, and noncompetitive antagonist of metabotropic glutamate
      receptor type 1.
AB  - Metabotropic glutamate receptor type 1 (mGluR1) is thought to play important
      roles in the neurotransmission and pathogenesis of several neurological
      disorders. Here, we describe the radioligand binding properties and
      pharmacological effects of a newly synthesized, high-affinity, selective, and
      noncompetitive mGluR1 antagonist, 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2
      a]benzimidazole-2-carboxamide (YM-298198). YM-298198 inhibited glutamate-induced
      inositol phosphate production in mGluR1-NIH3T3 cells with an IC50 of 16 +/- 5.8
      nM in a noncompetitive manner. Its radiolabeled form, [3H]YM-298198, bound to
      mGluR1-NIH3T3 cell membranes with a KD of 32 +/- 8.5 nM and a Bmax of 2297 +/-
      291 fmol/mg protein. In ligand displacement experiments using rat cerebellum
      membrane, an existing noncompetitive mGluR1 antagonist 7-(hydroxyimino)cyclo
      propa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) competitively displaced
      [3H]YM-298198 binding, although glutamate and other mGluR1 ligands acting on a
      glutamate site failed to inhibit [3H]YM-298198 binding, suggesting that YM-298198
      binds to CPCCOEt (allosteric) binding sites but not to glutamate (agonist)
      binding sites. Specificity was demonstrated for mGluR1 over mGluR subtypes 2 to
      7, ionotropic glutamate receptors, and other receptor, transporter, and ion
      channel targets. In in vivo experiments, orally administered YM-298198 showed a
      significant analgesic effect in streptozotocin-induced hyperalgesic mice at doses
      (30 mg/kg) that did not cause Rotarod performance impairment, indicating that it
      is also useful even for in vivo experiments. In conclusion, YM-298198 is a newly
      synthesized, high-affinity, selective, and noncompetitive antagonist of mGluR1
      that will be a useful pharmacological tool due to its highly active properties in
      vitro and in vivo. Its radiolabeled form [3H]YM-298198 will also be a valuable
      tool for future investigation of the mGluR1.

PMID- 15976017
TI  - Proerectile effects of the Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5
      isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the rat penis.
AB  - The Rho-kinase pathway mediates Ca2+ sensitization in the penile circulation,
      which maintains the penis in the flaccid state. We aimed to investigate the
      functional effect of a novel Rho-kinase inhibitor, H-1152 [(S)-(+)-2-methyl-1-[(4
      methyl-5-isoquinolinyl)sulfonyl]homopiperazine], both in vitro and in vivo as
      well as to demonstrate the expression of Rho guanine nucleotide exchange factors
      (RhoGEFs) in the rat corpus cavernosum (CC), by using a semiquantitative reverse
      transcription-polymerase chain reaction assay to measure their mRNA expression.
      Cumulative addition of H-1152 (0.001-3 microM) or Y-27632 [0.01-30 microM; (R)
      (+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide] caused sustained
      relaxations of precontracted CC strips, which were not affected by inhibition of
      the nitric oxide signaling pathway. Addition of H-1152 (0.1 microM), Y-27632 (1
      microM), or sodium nitroprusside (SNP; 0.1 microM) caused rightward shifts in the
      curves to phenylephrine (PE), but it had little effect on the contractions
      mediated by electrical field stimulation (EFS). It is noteworthy that when H-1152
      or Y-27632 was combined with SNP, a marked synergistic inhibition was noted both
      on PE- and EFS-induced contractions. Intraperitoneal administration of H-1152
      (100 nmol/kg) had a discrete effect on mean arterial pressure and significantly
      enhanced erectile responses evoked by stimulation of the cavernous nerve. The
      mRNA expression for PDZ-RhoGEF, p115RhoGEF, and leukemia-associated RhoGEF in
      cavernosal segments was visualized by electrophoresis on agarose gel. The results
      indicate that H-1152 is a powerful Rho-kinase inhibitor, giving rise to its
      therapeutic potential in the treatment of erectile dysfunction. The regulator of
      G-protein signaling-containing RhoGEFs may represent key components of the
      molecular mechanisms associated with the abnormal function of the cavernosal
      smooth muscle.

PMID- 15976018
TI  - Oral delivery and gastrointestinal absorption of soluble glucans stimulate
      increased resistance to infectious challenge.
AB  - Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and
      certain bacteria. We examined the pharmacokinetics of three water-soluble glucans
      (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1
      mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred
      at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between
      0.5 and 12 h. At 24 h, 27 +/- 3% of the glucan phosphate and 20 +/- 7% of the
      laminarin remained in the serum. Scleroglucan was rapidly absorbed and
      eliminated. The liver did not significantly contribute to the clearance of plasma
      glucan. Biological effects were further studied in mice. Following oral
      administration of 1 mg, glucans were bound and internalized by intestinal
      epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization
      of glucan by intestinal epithelial cells was not Dectin-dependent. GALT
      expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased
      following oral administration of glucan. Oral glucan increased systemic levels of
      interleukin (IL)-12 (151 +/- 15%) in mice. Oral glucan administration also
      increased survival in mice challenged with Staphylococcus aureus or Candida
      albicans. These data demonstrate that orally administered water-soluble glucans
      translocate from the gastrointestinal (GI) tract into the systemic circulation.
      The glucans are bound by GI epithelial and GALT cells, and they modulate the
      expression of pattern recognition receptors in the GALT, increase IL-12
      expression, and induce protection against infectious challenge.

PMID- 15976019
TI  - The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis.
AB  - Rho GTPases regulate reorganization of actin and microtubule cytoskeletal
      structures during both interphase and mitosis. The timing and subcellular
      compartment in which Rho GTPases are activated is controlled by the large family
      of Rho GTP exchange factors (RhoGEFs). Here, we show that the microtubule
      associated RhoGEF Lfc is required for the formation of the mitotic spindle during
      prophase/prometaphase. The inability of cells to assemble a functioning spindle
      after Lfc inhibition resulted in a delay in mitosis and an accumulation of
      prometaphase cells. Inhibition of Lfc's primary target Rho GTPase during
      prophase/prometaphase, or expression of a catalytically inactive mutant of Lfc,
      also prevented normal spindle assembly and resulted in delays in mitotic
      progression. Coinjection of constitutively active Rho GTPase rescued the spindle
      defects caused by Lfc inhibition, suggesting the requirement of RhoGTP in
      regulating spindle assembly. Lastly, we implicate mDia1 as an important effector
      of Lfc signaling. These findings demonstrate a role for Lfc, Rho, and mDia1
      during mitosis.

PMID- 15976020
TI  - The human brain is intrinsically organized into dynamic, anticorrelated
      functional networks.
AB  - During performance of attention-demanding cognitive tasks, certain regions of the
      brain routinely increase activity, whereas others routinely decrease activity. In
      this study, we investigate the extent to which this task-related dichotomy is
      represented intrinsically in the resting human brain through examination of
      spontaneous fluctuations in the functional MRI blood oxygen level-dependent
      signal. We identify two diametrically opposed, widely distributed brain networks
      on the basis of both spontaneous correlations within each network and
      anticorrelations between networks. One network consists of regions routinely
      exhibiting task-related activations and the other of regions routinely exhibiting
      task-related deactivations. This intrinsic organization, featuring the presence
      of anticorrelated networks in the absence of overt task performance, provides a
      critical context in which to understand brain function. We suggest that both task
      driven neuronal responses and behavior are reflections of this dynamic, ongoing,
      functional organization of the brain.

PMID- 15976021
TI  - Coevolutionary arms races between bacteria and bacteriophage.
AB  - We propose a computational and theoretical framework for analyzing rapid
      coevolutionary dynamics of bacteriophage and bacteria in their ecological
      context. Bacteriophage enter host cells via membrane-bound surface receptors
      often responsible for nutrient uptake. As such, a selective pressure will exist
      for the bacteria to modify its receptor configuration and, in turn, for the phage
      to modify its tail fiber. A mathematical model of these trait adaptations is
      developed by using the framework of adaptive dynamics. Host strains differ in
      their efficiency of resource uptake and resistance to phage, whereas phage
      strains differ in their host preference for adsorption. We solve the evolutionary
      ecology model and find the conditions for coevolutionary branching and relevant
      dimensionless parameters leading to distinct quasispecies. We confirm these
      calculations using stochastic Monte Carlo simulations of populations evolving in
      a chemostat with fixed washout rate and inflow resource density. We find that
      multiple quasispecies of bacteria and phage can coexist in a homogeneous medium
      with a single resource. When diversification occurs, quasispecies of phage adsorb
      effectively to only a limited subset of the total number of quasispecies of
      bacteria, i.e., functional differences between quasispecies arise endogenously
      within the evolutionary ecology framework. Finally, we discuss means to relate
      predictions of this model to experimental studies in the chemostat, using the
      model organisms Escherichia coli and the virulent strain of lambda phage.

PMID- 15976022
TI  - Reduced water density at hydrophobic surfaces: effect of dissolved gases.
AB  - Here, direct noninvasive neutron reflectivity measurements reveal the presence of
      a reduced (deuterated) water density region, with a sigmoidal density profile at
      the hydrophobic silane-water interface that depends on the type and concentration
      of dissolved gases in the water. Removal of dissolved gases decreases the width
      of the reduced water density region, and their reintroduction leads to its
      increase. When compared with recent computer simulations, a locally fluctuating
      density profile is proposed, whereas preexisting nanobubbles are excluded. The
      presence of a fluctuating reduced water density region between two hydrophobic
      surfaces and the attractive "depletion force" to which it leads may help explain
      the hydrophobic force and its reported diminution in deaerated water. Our results
      are also quantitatively consistent with recent dynamic surface force apparatus
      results that drastically revise previous estimates of the slip length of water
      flowing past hydrophobic surfaces from microns to approximately 20 nm. Our
      observations, therefore, go a long way toward reconciling three quite different
      types of experiments and phenomena: water depletion at hydrophobic surfaces,
      water slip at hydrophobic surfaces, and the hydrophobic interaction.

PMID- 15976023
TI  - The distribution of response spectra in the lateral geniculate nucleus compared
      with reflectance spectra of Munsell color chips.
AB  - This paper compares the spectral response curves of cells in the lateral
      geniculate nucleus (LGN) with the reflectance spectra of a large sample of
      Munsell color chips. By examining the color chips with methods used by neural
      response researchers and the LGN cells with methods used by psychophysical color
      researchers, we obtain insights that may be useful for advancing knowledge in
      both fields. For LGN cells, the prevailing view is that they tend to be clustered
      into distinct types or along discernible lines or planes when data obtained from
      selected light stimuli are represented in a three-dimensional space derived from
      cone contributions. In contrast, the Munsell color chips are viewed as rather
      evenly distributed in a three-dimensional perceptual space based on the
      psychophysical judgment of surface colors. We demonstrate that, when the Munsell
      chips are viewed in the space typically applied to LGN cells, the distribution
      appears similar to that of the cells and vice versa. We show why this result
      occurs and suggest that it has implications for studies in both fields.

PMID- 15976024
TI  - On class differentials in educational attainment.
AB  - Social class differentials in educational attainment have been extensively
      studied in numerous countries. In this paper, we begin by examining class
      differentials in the progression to higher secondary education among 16-year-old
      children in England and Wales. As has been shown for other countries, the
      differentials result both from the primary effects of differing levels of
      academic performance of children of different class background and from the
      secondary effects of differences in the educational choices that these children
      make at given levels of performance. Through counterfactual analyses in which the
      performance distribution of one class is combined with the choice distribution of
      another, primary and secondary effects are decomposed and the former are shown to
      be roughly three times the size of the latter.

PMID- 15976026
TI  - Sparse nonnegative solution of underdetermined linear equations by linear
      programming.
AB  - Consider an underdetermined system of linear equations y = Ax with known y and d
      x n matrix A. We seek the nonnegative x with the fewest nonzeros satisfying y =
      Ax. In general, this problem is NP-hard. However, for many matrices A there is a
      threshold phenomenon: if the sparsest solution is sufficiently sparse, it can be
      found by linear programming. We explain this by the theory of convex polytopes.
      Let a(j) denote the jth column of A, 1 < or = j < or = n, let a0 = 0 and P denote
      the convex hull of the a(j). We say the polytope P is outwardly k-neighborly if
      every subset of k vertices not including 0 spans a face of P. We show that
      outward k-neighborliness is equivalent to the statement that, whenever y = Ax has
      a nonnegative solution with at most k nonzeros, it is the nonnegative solution to
      y = Ax having minimal sum. We also consider weak neighborliness, where the
      overwhelming majority of k-sets of a(j)s not containing 0 span a face of P. This
      implies that most nonnegative vectors x with k nonzeros are uniquely recoverable
      from y = Ax by linear programming. Numerous corollaries follow by invoking
      neighborliness results. For example, for most large n by 2n underdetermined
      systems having a solution with fewer nonzeros than roughly half the number of
      equations, the sparsest solution can be found by linear programming.

PMID- 15976025
TI  - The evolution of vertebrate Toll-like receptors.
AB  - The complete sequences of Takifugu Toll-like receptor (TLR) loci and gene
      predictions from many draft genomes enable comprehensive molecular phylogenetic
      analysis. Strong selective pressure for recognition of and response to pathogen
      associated molecular patterns has maintained a largely unchanging TLR recognition
      in all vertebrates. There are six major families of vertebrate TLRs. This
      repertoire is distinct from that of invertebrates. TLRs within a family recognize
      a general class of pathogen-associated molecular patterns. Most vertebrates have
      exactly one gene ortholog for each TLR family. The family including TLR1 has more
      species-specific adaptations than other families. A major family including TLR11
      is represented in humans only by a pseudogene. Coincidental evolution plays a
      minor role in TLR evolution. The sequencing phase of this study produced finished
      genomic sequences for the 12 Takifugu rubripes TLRs. In addition, we have
      produced >70 gene models, including sequences from the opossum, chicken, frog,
      dog, sea urchin, and sea squirt.

PMID- 15976027
TI  - Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of
      hypertrophic chondrocytes.
AB  - Rickets is seen in association with vitamin D deficiency and in several genetic
      disorders associated with abnormal mineral ion homeostasis. Studies in vitamin D
      receptor (VDR)-null mice have demonstrated that expansion of the late
      hypertrophic chondrocyte layer, characteristic of rickets, is secondary to
      impaired apoptosis of these cells. The observation that normalization of mineral
      ion homeostasis in the VDR-null mice prevents rachitic changes suggests that
      rickets is secondary to hypocalcemia, hypophosphatemia, or hyperparathyroidism,
      rather than impaired VDR action. To determine which of these abnormalities is
      responsible for impaired chondrocyte apoptosis and subsequent rachitic changes,
      two additional models were examined: diet-induced hypophosphatemia/hypercalcemia
      and hypophosphatemia secondary to mutations in the Phex gene. The former model is
      associated with suppressed parathyroid hormone levels as a consequence of
      hypercalcemia. The latter model demonstrates normal calcium and parathyroid
      hormone levels, but 1,25-dihydroxyvitamin D levels that are inappropriately low
      for the degree of hypophosphatemia. Our studies demonstrate that normal
      phosphorus levels are required for growth plate maturation and implicate a
      critical role for phosphate-regulated apoptosis of hypertrophic chondrocytes via
      activation of the caspase-9-mediated mitochondrial pathway.

PMID- 15976028
TI  - IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation.
AB  - Interleukin (IL)-6 signaling through its soluble receptor (IL-6 transsignaling)
      directs transition between innate and acquired immune responses by orchestrating
      the chemokine-directed attraction and apoptotic clearance of leukocytes. Through
      analysis of mononuclear cell infiltration in WT and IL-6-deficient mice during
      peritoneal inflammation, we now report that IL-6 selectively governs T cell
      infiltration by regulating chemokine secretion (CXCL10, CCL4, CCL5, CCL11, and
      CCL17) and chemokine receptor (CCR3, CCR4, CCR5, and CXCR3) expression on the
      CD3+ infiltrate. Although blockade of IL-6 trans-signaling prevented chemokine
      release, chemokine receptor expression remained unaltered suggesting that this
      response is regulated by IL-6 itself. To dissect the signaling events promoting T
      cell migration, inflammation was established in knock-in mice expressing mutated
      forms of the universal signal-transducing element for IL-6-related cytokines
      gp130. In mice (gp130Y757F/Y757F) deficient in SHP2 and SOCS3 binding, but
      presenting hyperactivation of STAT1/3, T cell recruitment and CCL5 expression was
      enhanced. Conversely, both of these parameters were suppressed in mice with
      ablated gp130-mediated STAT1/3 activation (gp130DeltaSTAT/DeltaSTAT). T cell
      migration was related to STAT3 activity, because monoallelic deletion of Stat3 in
      gp130(Y757F/Y757F) mice (gp130Y757F/Y757F:Stat3+/-) corrected the exaggerated
      responses observed in gp130Y757F/Y757F mice. Consequently, STAT3 plays a defining
      role in IL-6-mediated T cell migration.

PMID- 15976029
TI  - The impact of HIV/AIDS on the control of tuberculosis in India.
AB  - Epidemics of HIV/AIDS have increased the tuberculosis (TB) case-load by five or
      more times in East Africa and southern Africa. As HIV continues to spread,
      warnings have been issued of disastrous AIDS and TB epidemics in "new-wave"
      countries, including India, which accounts for 20% of all new TB cases arising in
      the world each year. Here we investigate whether, in the face of the HIV
      epidemic, India's Revised National TB Control Program (RNTCP) could halve TB
      prevalence and death rates in the period 1990-2015, as specified by the United
      Nations Millennium Development Goals. Using a mathematical model to capture the
      spatial and temporal variation in TB and HIV in India, we predict that, without
      the RNTCP, HIV would increase TB prevalence (by 1%), incidence (by 12%), and
      mortality rates (by 33%) between 1990 and 2015. With the RNTCP, however, we
      expect substantial reductions in prevalence (by 68%), incidence (by 41%), and
      mortality (by 39%) between 1990 and 2015. In India, 29% of adults but 72% of HIV
      positive adults live in four large states in the south where, even with the
      RNTCP, mortality is expected to fall by only 15% between 1990 and 2015.
      Nationally, the RNTCP should be able to reverse the increases in TB burden due to
      HIV but, to ensure that TB mortality is reduced by 50% or more by 2015, HIV
      infected TB patients should be provided with antiretroviral therapy in addition
      to the recommended treatment for TB.

PMID- 15976030
TI  - Extreme hyperopia is the result of null mutations in MFRP, which encodes a
      Frizzled-related protein.
AB  - Nanophthalmos is a rare disorder of eye development characterized by extreme
      hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00
      diopters. Because the cornea and lens are normal in size and shape, hyperopia
      occurs because insufficient growth along the visual axis places these lensing
      components too close to the retina. Nanophthalmic eyes show considerable
      thickening of both the choroidal vascular bed and scleral coat, which provide
      nutritive and structural support for the retina. Thickening of these tissues is a
      general feature of axial hyperopia, whereas the opposite occurs in myopia. We
      have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified
      four independent mutations in MFRP, a gene that is selectively expressed in the
      eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding
      domain of the Frizzled transmembrane receptors. This gene is not critical for
      retinal function, as patients entirely lacking MFRP can still have good
      refraction-corrected vision, produce clinically normal electro-retinograms, and
      show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears
      primarily devoted to regulating axial length of the eye. It remains to be
      determined whether natural variation in its activity plays a role in common
      refractive errors.

PMID- 15976032
TI  - Critical period for sensory experience-dependent survival of newly generated
      granule cells in the adult mouse olfactory bulb.
AB  - Granule cells in the olfactory bulb (OB) are continually produced and added into
      the neuronal circuit in the adult brain. Sensory input to the OB plays a key role
      in the survival of newly generated granule cells. Here, we examined in the adult
      mice whether there is a time window after the generation of new granule cells
      when their survival is strongly influenced by sensory input. New granule cells
      were labeled by BrdUrd injection, and the mice were deprived of sensory input
      unilaterally by naris cauterization. During the initial 14 days after BrdUrd
      labeling, the number of BrdUrd-positive granule cells was similar for deprived
      and undeprived OBs. At 28 days or later, the BrdUrd-positive cell number
      remarkably decreased in the deprived OB. Cauterization at days 14-28 effectively
      reduced the number of BrdUrd-positive granule cells, whereas 2-week cauterization
      before or after this period produced little effect. Administration of diazepam, a
      GABAA receptor modulator, decreased the number of BrdUrd-positive granule cells.
      The diazepam administration was most effective at days 14-28. Histochemical
      examination showed that activation of caspase-3 was accompanied by apoptotic cell
      death of granule cells that was induced by sensory deprivation or diazepam
      administration. Double labeling with activated caspase-3 and BrdUrd indicated
      that granule cells at days 14-20 were most susceptible to cell death. These
      results indicate that there is a critical period when the survival of new granule
      cells is determined in a sensory experience-dependent manner and that the
      pharmacological manipulation can mimic the effect of sensory deprivation.

PMID- 15976031
TI  - Structural and biochemical basis for selective repression of the orphan nuclear
      receptor liver receptor homolog 1 by small heterodimer partner.
AB  - The functional interaction between the orphan nuclear receptors small heterodimer
      partner (SHP) and liver receptor homolog 1 (LRH-1), where SHP binds to LRH-1 and
      represses its constitutive transcriptional activity, is crucial for regulating
      genes involved in cholesterol homeostasis. Here, we report structural and
      biochemical analyses of the LRH-1/SHP interaction. The crystal structure and
      modeling studies of the LRH-1 ligand-binding domain bound to either of the two
      LXXLL-related motifs of SHP show that the receptor undergoes conformational
      changes to accommodate the SHP docking and reveal key residues that determine the
      potency and selectivity of SHP binding. Through a combination of mutagenesis and
      binding studies, we demonstrate that only the second SHP LXXLL motif is required
      for repressing LRH-1, and this motif displays a strong preference for binding to
      LRH-1 over the closely related receptor steroidogeneic factor 1 (SF-1).
      Structural comparisons indicate that this binding selectivity is determined by
      residues flanking the core LXXLL motifs. These results establish a structural
      model for understanding how SHP interacts with LRH-1 to regulate cholesterol
      homeostasis and provide new insights into how nuclear receptor/coregulator
      selectivity is achieved.

PMID- 15976033
TI  - Involvement of IL-6 in the anti-human immunodeficiency virus activity of IFN-tau
      in human macrophages.
AB  - IFN-tau is a non-cytotoxic type I IFN responsible for maternal recognition of the
      foetus in ruminants. IFN-tau has been found to inhibit HIV replication more
      strongly than human IFN-alpha, particularly in human monocyte-derived
      macrophages, without associated toxicity. Ovine IFN-tau uses the same anti-viral
      cellular pathways as human IFN-alpha in human macrophages, principally inhibiting
      the early steps of the biological cycle of HIV, preventing the integration of HIV
      DNA into the host-cell genome. In this study, we investigated the
      immunomodulatory properties of IFN-tau in human macrophages. We found that IFN
      tau increased the production of IL-10 and IL-6, but not of IL-1beta or tumour
      necrosis factor alpha, in unstimulated, LPS-stimulated and HIV-1/Ba-L-infected
      macrophages. We also found that treatment with IL-6 inhibited HIV replication.
      Moreover, the neutralization of IL-6 activity in the cell culture supernatants of
      IFN-tau-treated macrophages led to a decrease in the anti-retroviral effects of
      IFN-tau, suggesting that IL-6 was involved in the anti-viral activity induced by
      IFN-tau. By focusing on the very early steps of the biological cycle of HIV, we
      showed that IL-6 co-operated with IFN-tau to decrease intracellular HIV RNA
      levels 2 h after infection.

PMID- 15976034
TI  - Autistic effector T cells in mice with a point mutation in the LAT adaptor fail
      to respond to Listeria monocytogenes infection.
AB  - The adaptor protein linker for activation of T cells (LAT) is an important
      transducer of extracellular T cell stimuli. In mice with a point mutation in LAT
      (LatY136F), TCR signaling is substantially compromised and LatY136F T cells are
      unresponsive to CD3 cross-linking in vitro. Nevertheless, LatY136F mice develop a
      polyclonal lymphoproliferation of CD4(+) T cells, which display a T(h)2-polarized
      effector phenotype. In this study, LatY136F mice were infected with the
      intracellular bacterium Listeria monocytogenes and the antigen-specific responses
      of T cells were determined. Both CD4(+) and CD8(+) LatY136F T cells were
      unresponsive to L. monocytogenes infection. In contrast, when CD4(+) T cells from
      wild-type mice were adoptively transferred into LatY136F hosts, they responded
      normally to L. monocytogenes, indicating that the LatY136F milieu permits T(h)1
      responses. Furthermore, we analyzed whether the infection would influence the
      capacity of LatY136F CD4(+) T cells to produce IL-4 and IFN-gamma. While L.
      monocytogenes infection results in T(h)1-type T cell responses in wild-type
      animals, we found that it did not shift the strong T(h)2 polarization of LatY136F
      T cells towards a T(h)1 pattern. In conclusion, our results suggest that the
      activation and T(h)2 polarization of the LatY136F CD4(+) T cells is not
      influenced by infection with an intracellular pathogen known to induce robust
      T(h)1 responses, and is thus likely driven by T cell intrinsic mechanisms.

PMID- 15976035
TI  - Monitoring the activation state of the insulin-like growth factor-1 receptor and
      its interaction with protein tyrosine phosphatase 1B using bioluminescence
      resonance energy transfer.
AB  - We have developed two bioluminescence resonance energy transfer (BRET)-based
      approaches to monitor 1) ligand-induced conformational changes within partially
      purified insulin-like growth factor-1 (IGF-1) receptors (IGF1R) and 2) IGF1R
      interaction with a substrate-trapping mutant of protein tyrosine phosphatase 1B
      (PTP1B-D181A) in living cells. In the first assay, human IGF1R fused to Renilla
      reniformis luciferase (Rluc) or yellow fluorescent protein (YFP) were
      cotransfected in human embryonic kidney (HEK)-293 cells. The chimeric receptors
      were then partially purified by wheat germ lectin chromatography, and BRET
      measurements were performed in vitro. In the second assay, BRET measurements were
      performed on living HEK-293 cells cotransfected with IGF1R-Rluc and YFP-PTP1B
      D181A. Ligand-induced conformational changes within the IGF1R and interaction of
      the IGF1R with PTP1B could be detected as an energy transfer between Rluc and
      YFP. Dose-response experiments with IGF-1, IGF-2, and insulin demonstrated that
      the effects of these ligands on BRET correlate well with their known
      pharmacological properties toward the IGF1R. Inhibition of IGF1R
      autophosphorylation by the tyrphostin AG1024 (3-bromo-5-t-butyl-4-hydroxy
      benzylidenemalonitrile) resulted in the inhibition of IGF1-induced BRET signal
      between the IGF1R and PTP1B. In addition, an anti-IGF1R antibody known to inhibit
      the biological effects of IGF-1 inhibited ligand-induced BRET signal within the
      IGF1R, as well as between IGF1R and PTP1B. This inhibition of BRET signal
      paralleled the inhibition of the ligand-induced autophosphorylation of the IGF1R
      by this antibody. In conclusion, these BRET-based assays permit 1) the rapid
      evaluation of the effects of agonists or inhibitory molecules on IGF1R activation
      and 2) the analysis of the regulation of IGF1R-PTP1B interaction in living cells.

PMID- 15976036
TI  - HIV protease inhibitors activate the unfolded protein response in macrophages:
      implication for atherosclerosis and cardiovascular disease.
AB  - Human immunodeficiency virus (HIV) protease inhibitors have been successfully
      used in highly active antiretroviral therapy for HIV-1 infection. Treatment of
      patients infected with HIV with HIV protease inhibitors is unfortunately
      associated with a number of clinically significant metabolic abnormalities and an
      increased risk of premature atherosclerosis and myocardial infarction. However,
      the cellular/molecular mechanisms of the HIV protease inhibitor-induced lipid
      dysregulation and atherosclerosis remain elusive. Macrophages are the most
      prominent cell type present in atherosclerotic lesions and play essential roles
      in both early lesion development and late lesion complications. In this study, we
      demonstrate that three different HIV protease inhibitors (ritonavir, indinavir,
      and atazanavir) induce endoplasmic reticulum stress and activate the unfolded
      protein response in mouse macrophages. Furthermore, at therapeutic concentrations
      (5-15 microM), these HIV protease inhibitors were found to increase the levels of
      transcriptionally active sterol regulatory element binding proteins, decrease
      endogenous cholesterol esterification, cause the accumulation of free cholesterol
      in intracellular membranes, deplete endoplasmic reticulum calcium stores,
      activate caspase-12, and increase apoptosis in macrophages. These findings
      provide possible cellular mechanisms by which HIV protease inhibitors promote
      atherosclerosis and cardiovascular disease in HIV-1 infected patients treated
      with HIV protease inhibitors.

PMID- 15976037
TI  - Gallotannin inhibits the expression of chemokines and inflammatory cytokines in
      A549 cells.
AB  - Tannins are plant-derived water-soluble polyphenols with wide-ranging biological
      activities. The mechanisms underlying the anti-inflammatory effect of tannins are
      not fully understood and may be the result of inhibition of poly(ADP-ribose)
      (PAR) glycohydrolase (PARG), the main catabolic enzyme of PAR metabolism.
      Therefore, we set out to investigate the mechanism of the anti-inflammatory
      effect of gallotannin (GT) in A549 cells with special regard to the role of
      poly(ADP-ribosyl)ation. Using an inflammation-focused low-density array and
      reverse transcription-polymerase chain reaction, we found that GT suppressed the
      expression of most cytokines and chemokines in cytokine-stimulated A549 cells,
      whereas the PARP inhibitor PJ-34 only inhibited few transcripts. Activation of
      the transcription factors, nuclear factor kappaB (NF-kappaB) and activator
      protein 1 (AP-1), was blocked by GT, whereas PJ-34 only suppressed NF-kappaB
      activation but not AP-1 activation. GT also inhibited IkappaB phosphorylation and
      nuclear translocation of NF-kappaB, but PJ-34 had no effect on these upstream
      events. In the AP-1 pathway, GT treatment, even in the absence of cytokines,
      caused maximal phosphorylation of c-Jun N-terminal kinase and c-Jun. GT also
      caused a low-level phosphorylation of p38, extracellular signal-regulated kinases
      1 and 2, activating transcription factor2, and cAMP-response element-binding
      protein but inhibited cytokine-induced phosphorylation of these kinases and
      transcription factors. GT inhibited protein phosphatases 1 and 2A, which may
      explain the increased phosphorylation of mitogen-activated protein kinase and
      their substrates. GT exerted potent antioxidant effect but failed to cause PAR
      accumulation. In summary, the potent inhibitory effects of GT on the
      transcription of cytokine and chemokine genes are probably not related to PARG
      inhibition. Inhibition of AP-1 activation and upstream signaling events may be
      responsible for the effects of GT.

PMID- 15976038
TI  - Novel potent human ether-a-go-go-related gene (hERG) potassium channel enhancers
      and their in vitro antiarrhythmic activity.
AB  - A variety of drugs has been reported to cause acquired long QT syndrome through
      inhibition of the IKr channel. Screening compounds in early discovery and
      development stages against their ability to inhibit IKr or the hERG channel has
      therefore become an indispensable procedure in the pharmaceutical industry. In
      contrast to numerous hERG channel blockers discovered during screening, only
      (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)
      prop-2-ynyl]-piperidine-3-carboxylic acid (RPR260243) has been reported so far to
      enhance the hERG current. In this article, we describe several potent
      mechanistically distinct hERG channel enhancers. One example is PD-118057 (2-{4
      [2-(3,4-dichloro-phenyl)-ethyl]-phenylamino}-benzoic acid) which produced average
      increases of 5.5 +/- 1.1, 44.8 +/- 3.1, and 111.1 +/- 21.7% in the peak tail hERG
      current at 1, 3, and 10 muM, respectively, in human embryonic kidney 293 cells.
      PD-118057 did not affect the voltage dependence and kinetics of gating
      parameters, nor did it require open conformation of the channel. In isolated
      guinea pig cardiomyocytes, PD-118057 showed no major effect on I(Na), I(Ca,L),
      I(K1), and I(Ks). PD-118057 shortened the action potential duration and QT
      interval in arterially perfused rabbit ventricular wedge preparation in a
      concentration-dependent manner. The presence of 3 muM PD-118057 prevented action
      potential duration and QT prolongation caused by dofetilide. "Early after
      depolarizations" induced by dofetilide were also completely eliminated by 3
      microM PD-118057. Although further investigation is warranted to evaluate the
      therapeutic value and safety profile of these compounds, our data support the
      notion that hERG activation by pharmaceuticals may offer a new approach in the
      treatment of delayed repolarization conditions, which may occur in patients with
      inherited or acquired long QT syndrome, congestive heart failure, and diabetes.

PMID- 15976039
TI  - Symbols and meanings in academia.

PMID- 15976040
TI  - Myth and symbol in nursing theories.
AB  - Nursing theories are like myths, in that they contain symbolic representations
      that tell a story about nursing, and these stories represent or explain nursing's
      image, worldview, beliefs, and practices. Five theories are analyzed to identify
      the myths that they represent. It is proposed that uncovering the myth in nursing
      theories will help to communicate nursing brands that convey the essence and
      value of nursing.

PMID- 15976041
TI  - Adaptation to cesarean birth: implementation of an international multisite study.
AB  - The purpose of this column is to describe the implementation of an international
      multisite Roy adaptation model-based study of women's perceptions of and
      responses to cesarean birth. The need for the study arose from the concern that
      women's childbearing needs may not be met to their full satisfaction, especially
      if the infant is born by cesarean. Serendipity and networking played a part in
      the selection of four study sites in the United States (Boston, Milwaukee,
      Norfolk, Oklahoma City) and two in other countries (Finland, Australia). Data
      were collected by nursing students and staff nurses. Post-hoc consideration of
      the diversity of study sites revealed opportunities for examination of the
      influence of the contextual stimuli of culture and geographic region on the
      women's adaptation to cesarean birth. Strategies used to foster integration of
      teaching, practice, and research are discussed.

PMID- 15976042
TI  - Symbols and ethics: integrity and the discipline of nursing.
AB  - Symbols give meaning to phenomena coconstituted in the human-universe-health
      process. There are many common symbols of ethics found in the discipline of
      nursing. Symbols of ethics may take the form of codes, oaths, pledges,
      resolutions, or position statements that represent notions of what one ought to
      do in a discipline or profession. Ethical symbols are intended to guide a
      particular discipline in practice, research, and education. What is their
      importance to the discipline of nursing? What are the possible implications of
      integrity for nursing when viewing the application of ethical symbols from a
      nursing theoretical perspective?

PMID- 15976043
TI  - The experience of the novice nurse: a human becoming perspective.
AB  - The well-publicized current shortage of nurses and nurse faculty to teach future
      generations of nurses intensifies the need to recruit and retain nurses engaged
      in professional practice. This suggests the importance of being concerned with
      the quality of the work and professional life of the practicing professional
      nurse. In this column, the stories of 10 new graduates of baccalaureate nursing
      programs are explored, illuminating experiences of novice nurses. Themes of the
      new graduates were identified. The themes are: learning a new culture, sharing a
      journey, being unsure with changing views, considering the possibilities, and
      being respected. It is hoped that this column will further the dialogue and
      promote projects among nurses to explore possibilities in originating new ways of
      being and becoming in nursing practice.

PMID- 15976044
TI  - Human becoming theory with children.
AB  - As a nurse practitioner, I am often challenged with providing care for children
      in the traditional medical model. Struggling with these challenges has created
      new ways of being with patients and their families. Working with children is
      gratifying, stimulating, and life changing. Living true presence with children as
      they draw images of their realities gives rise to a powerful interconnectedness
      that facilitates greater understanding of their meaning about what is important
      to them as they create new ways of seeing health opportunities. Bearing witness
      to children as they use art and words to describe their feelings encourages and
      fosters new ways of becoming for the nurse and the child and the child's family.
      This column describes a dialogical-engagement of this nurse practitioner and a
      young child and how this process transformed the nurse practitioner as she moves
      to be with children and families in new ways.

PMID- 15976045
TI  - Influences on advancement of nursing knowledge. Interview by Jacqueline Fawcett.
AB  - This column presents a dialogue between Martha Raile Alligood and Jacqueline
      Fawcett about the factors that have facilitated and factors that have impeded the
      growth of nursing knowledge, as well as comments on strategies for effective
      teaching of nursing conceptual models and theories.

PMID- 15976046
TI  - Grieving a loss: the lived experience for elders residing in an institution.
AB  - Grieving a loss is a profound and universal human experience. This
      phenomenological-hermeneutic study was an inquiry into the lived experience of
      grieving a loss. The nursing perspective was Parse's human becoming theory.
      Participants were 10 elderly persons residing in a long-term care facility. The
      study finding specifies the structure of the lived experience of grieving a loss
      as aching solitude amid enduring cherished affiliations, as serene acquiescence
      arises with sorrowful curtailments. Findings are discussed in relation to the
      guiding theoretical perspective and related literature. Recommendations for
      additional research and insights for practice are presented.

PMID- 15976047
TI  - Unity of knowledge in the advancement of nursing knowledge.
AB  - During the past 20 years, we have witnessed an explosion in nursing knowledge
      providing the discipline with diverse and multifaceted theoretical frameworks and
      paradigms. One knowledge theme that pervades the dialogue in the scholarly
      literature is that of multiple ways of knowing. With the acknowledgement that the
      fundamental nature of nursing knowledge is grounded in the understanding of human
      nature and its response to its environment, comes an imperative for a consilience
      of knowledge. The purpose of this article is to present such a unified worldview
      by articulating a vision of nursing knowledge, a meaning of unity of knowledge,
      and a challenge to the discipline to embrace inclusive rather than exclusive ways
      of knowing.

PMID- 15976048
TI  - Orem's self-care deficit nursing theory: pediatric asthma as exemplar.
AB  - Asthma is the most frequent reason for preventable hospital admissions among
      children regardless of race or socioeconomic status. Since hospitalizations are
      preventable, a reasonable assumption is that parents are not optimally managing
      their child's asthma. Using Orem's self-care deficit nursing theory, 14
      conditions were uncovered in the pediatric asthma literature that influence
      development of competency by parents. Twelve of the 14 antecedent conditions are
      influenced by factors partly or completely controlled by the healthcare system.
      Healthcare system gaps associated with asthma symptom control have come to light
      through the articulation of the pediatric asthma literature and Orem's theory.

PMID- 15976049
TI  - Standing at the doorway looking in.
AB  - The challenges and opportunities for nurses who work with people from diverse
      backgrounds are considered. The task for a nurse from the dominant culture
      working with persons from minority cultures requires patience, sensitivity,
      humility, and imagination, but it can be well worth the effort for all involved.

PMID- 15976050
TI  - Nursing practice with Aboriginal communities: expanding worldviews.
AB  - Through advances in interpretive inquiry, diverse ways of knowing and
      experiencing reality are increasingly made explicit in nursing literature.
      Nevertheless, the privileges of empiricism continue alongside a lack of language
      to consider other realms of reality. In this column, Aboriginal ways of
      constituting health and reality are explored. Morley's four categorizations of
      health belief systems provide a useful tool for understanding diverse worldviews.
      In contrast, Atleo drew on Nuu-chah-nulth origin stories to address the
      complexities and ambiguities of Aboriginal health beliefs. Approaches for
      bridging cultural differences are explored with a view toward inclusive
      healthcare and nursing practice.

PMID- 15976051
TI  - Common (mis)perceptions about IRB review of human subjects research.
AB  - Every researcher who conducts research involving human subjects for their data
      has experiences with one or more institutional review boards. Some view their
      institutional review board experiences as helpful; others view them as painful
      and obstructive. However, there are many misperceptions about institutional
      review boards and their operation. Some common misperceptions are presented and
      discussed in an effort to correct false views held by researchers.

PMID- 15976052
TI  - Activation of caspase 8 in the pituitaries of streptozotocin-induced diabetic
      rats: implication in increased apoptosis of lactotrophs.
AB  - Lactotroph cell death is increased in streptozotocin-induced diabetic rats. To
      determine the mechanism involved, cell death proteins were accessed in
      pituitaries of diabetic (streptozotocin at 65 mg/kg, 2 months evolution) and
      control male rats by Western blot analysis and double immunohistochemistry. The
      intact and cleaved forms of caspase 9 were increased in diabetic rat pituitaries
      compared with controls. Although the proforms of caspases 3, 6, and 7 were
      increased in diabetic rat pituitaries, their activated forms were either
      unchanged or decreased. Activation of these effector caspases may be blocked by
      the increased expression of X-chromosome-linked inhibitor of apoptosis protein
      (XIAP) in diabetic rat pituitaries. However, in diabetic rats, XIAP expression in
      lactotrophs was decreased, suggesting that this cell type is not protected.
      Caspase 8, p53, and nuclear factor kappaB were more highly activated in diabetic
      rat pituitaries, with caspase 8 colocalization in lactotrophs being increased.
      These results suggest that, in the pituitaries of diabetic rats, the cascades of
      normal cell turnover are partially inhibited, possibly via XIAP, and this may be
      cell specific. Furthermore, activation of the extrinsic cell-death pathway,
      including activation of caspase 8, may underlie the diabetes-associated increase
      in lactotroph death.

PMID- 15976053
TI  - The estrogen receptor modulator tamoxifen enhances spontaneous glycinergic
      synaptic inhibition of hypoglossal motoneurons.
AB  - Tamoxifen (Tam), a widely used anticancer agent, is now also used for healthy
      women with risk of breast cancer. Furthermore, it is the prototype of the
      selective estrogen receptor modulator family, with promise for neuroprotection.
      However, possible effects on neurotransmission have been little explored.
      Recently, Tam was shown to potentiate chloride responses to low concentrations of
      exogenous glycine in cultured spinal neurons from rat embryo. The present study
      investigates the possible modulation by Tam of the spontaneous synaptic
      glycinergic activity recorded from voltage-clamped hypoglossal motoneurons, using
      the whole-cell patch-clamp technique in brainstem slices from juvenile rat.
      Miniature currents were isolated with tetrodotoxin. Tam increased the mean
      amplitude of glycinergic miniature currents, by 68-79% at 2 microM (in nine of 10
      cells) and by 47% at 0.5 microM (in four of nine cells). Furthermore, Tam
      markedly increased the frequency of glycinergic miniatures, by a factor reaching
      15 in some neurons, even in the presence of the Ca2+ channel blocker Cd2+. Tam
      also increased the frequency of the total spontaneous glycinergic activity
      without tetrodotoxin. The increase in miniature amplitude is consistent with the
      increase in postsynaptic glycine receptor sensitivity previously reported. The
      increase in frequency indicates an additional presynaptic effect. Addition of
      exogenous glycine could also increase the frequency of glycinergic miniatures.
      Thus, one of the presynaptic effects of Tam might be potentiation of the basal
      activity of presynaptic glycine receptors facilitating glycine release. Possible
      risks related to modulation of glycinergic neurotransmission by Tam should be
      considered when recommending its use in healthy individuals.

PMID- 15976054
TI  - Tetrahydrogestrinone is an androgenic steroid that stimulates androgen receptor
      mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and
      promotes muscle accretion in orchidectomized male rats.
AB  - The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led
      the U.S. Congress to declare it a controlled substance, although conclusive
      evidence of its anabolic/androgenic activity is lacking. We determined whether
      THG affects myogenic differentiation and androgen receptor (AR)-mediated
      signaling, whether it binds to AR, and whether it has androgenic and anabolic
      effects in vivo. Accordingly, we measured the dissociation constant for THG with
      a fluorescence anisotropy assay using recombinant AR-ligand binding domain. The
      AR nuclear translocation and myogenic activity of androstenedione were evaluated
      in mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of
      the THG:AR interaction. The androgenic/anabolic activity was evaluated in
      orchidectomized rats. THG bound to AR with an affinity similar to that of
      dihydrotestosterone. In multipotent C3H10T1/2 cells, THG upregulated AR
      expression, induced AR nuclear translocation, dose dependently increased the area
      of myosin heavy chain type II-positive myotubes, and up-regulated myogenic
      determination and myosin heavy chain type II protein expression. The interaction
      between AR and the A ring of THG was similar to that between AR and the A ring of
      dihydrotestosterone, but the C17 and C18 substituents in THG had a unique
      stabilizing interaction with AR. THG administration prevented the castration
      induced atrophy of levator ani, prostate gland, and seminal vesicles and loss of
      fat-free mass in orchidectomized rats. We conclude that THG is an anabolic
      steroid that binds to AR, activates AR-mediated signaling, promotes myogenesis in
      mesenchymal multipotent cells, and has anabolic and androgenic activity in vivo.
      This mechanism-based approach should be useful for rapid screening of
      anabolic/androgenic agents.

PMID- 15976055
TI  - Firing pattern and rapid modulation of activity by estrogen in primate
      luteinizing hormone releasing hormone-1 neurons.
AB  - We have shown previously that cultured LHRH-1 neurons, derived from monkey
      olfactory placode region, exhibit pulsatile LHRH-1 release at hourly intervals
      and spontaneous intracellular calcium oscillations, which synchronize at a
      frequency similar to LHRH-1 release. Brief application of estrogen induced a
      rapid increase in the frequency of intracellular calcium oscillations and the
      frequency of synchronizations. The estrogen-induced frequency of intracellular
      calcium oscillations was mediated by estrogen receptors (ER), whereas the
      frequency of synchronizations was not mediated by ER. In the present study, we
      further examined the rapid action of estrogen using patch-clamp recording in
      primate LHRH-1 neurons. Cell-attached patch-clamp recording showed that LHRH-1
      neurons exhibited monophasic or biphasic action currents that were sensitive to
      an increase in extracellular K+ and the sodium channel blocker tetrodotoxin. The
      majority (90%) of LHRH-1 neurons showed irregular firing patterns composed of
      bursts and irregular beatings of action currents, which further formed a
      "cluster" firing pattern. Brief application of 17beta-estradiol (1 nM) increased
      the firing frequency and burst duration of LHRH-1 neurons with a latency of 60
      120 sec for up to 25 min. ICI182,780, an ER antagonist, blocked the 17beta
      estradiol-induced increase in the firing activity of LHRH-1 neurons. These
      results suggest that 1) primate LHRH-1 neurons exhibit complex firing patterns
      composed of activities with different time domains, 2) estrogen causes rapid
      stimulatory action of firing activity, and 3) this estrogen action is mediated by
      ER in primate LHRH-1 neurons.

PMID- 15976056
TI  - Fetal programming: excess prenatal testosterone reduces postnatal luteinizing
      hormone, but not follicle-stimulating hormone responsiveness, to estradiol
      negative feedback in the female.
AB  - Exposure of female sheep fetuses to excess testosterone (T) during early to
      midgestation produces postnatal hypergonadotropism manifest as a selective
      increase in LH. This hypergonadotropism may result from reduced sensitivity to
      estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH.
      We tested the hypothesis that excess T before birth reduces responsiveness of LH
      and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T
      propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90
      gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of
      age in the ovary-intact female offspring. Our experimental strategy was first to
      arrest follicular growth and reduce endogenous E2 by administering the GnRH
      antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then
      provide a fixed amount of exogenous E2 via an implant. Blood samples were
      obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during
      and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH
      pulsatility, reduced FSH by approximately 25%, and E2 production diminished to
      near detection limit of assay at both ages in both groups. Prenatal T treatment
      produced a precocious and selective reduction in responsiveness of LH but not FSH
      to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse
      frequency. Collectively, these findings support the hypothesis that prenatal
      exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback
      of LH/GnRH secretion to contribute to the development of hypergonadotropism.

PMID- 15976057
TI  - Adiponectin gene is expressed in multiple tissues in the chicken: food
      deprivation influences adiponectin messenger ribonucleic acid expression.
AB  - Adiponectin is a cytokine hormone originally found to be secreted exclusively by
      white adipose tissue. However, recent evidences suggest that adiponectin is also
      produced in brown adipose tissue and skeletal muscle. The present study
      investigated the expression of adiponectin mRNA in various tissues in the
      chicken. We also studied the effect of food deprivation on adiponectin gene
      expression in adipose tissue, liver, anterior pituitary gland, and diencephalon
      in the chicken. The open reading frame of chicken adiponectin cDNA consists of
      735 nucleotides that were 65-68% homologous to various mammalian adiponectin
      cDNAs. The deduced amino acid sequence of chicken adiponectin contains 22 glycine
      X-Y repeats (in which X and Y represent any amino acid) at the N-terminal end as
      found in the mammalian adiponectin. By RT-PCR and Northern analysis, we detected
      chicken adiponectin mRNA transcript in adipose tissue, liver, anterior pituitary
      gland, diencephalon, skeletal muscle, liver, kidney, ovary, and spleen but not in
      blood. Adiponectin mRNA expression in various tissues was quantitated using real
      time quantitative PCR and found to be the highest in adipose tissue, followed by
      liver, anterior pituitary, diencephalon, kidney, and skeletal muscle. We also
      found that adiponectin mRNA quantity was significantly decreased after a 48-h
      food deprivation in adipose tissue, liver, and anterior pituitary gland but not
      in diencephalon. Our results provide novel evidence that, unlike mammals,
      adiponectin gene is expressed in several tissues in the chicken and that its
      expression is influenced by food deprivation.

PMID- 15976058
TI  - Involvement of central metastin in the regulation of preovulatory luteinizing
      hormone surge and estrous cyclicity in female rats.
AB  - Ovulation is caused by a sequence of neuroendocrine events: GnRH and LH surges
      that are induced by positive feedback action of estrogen secreted by the mature
      ovarian follicles. The central mechanism of positive feedback action of estrogen
      on GnRH/LH secretion, however, is not fully understood yet. The present study
      examined whether metastin, the product of metastasis suppressor gene KiSS-1, is a
      central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the
      female rat. Metastin had a profound stimulation on LH secretion by acting on the
      preoptic area (POA), where most GnRH neurons projecting to the median eminence
      are located, because injection of metastin into the third ventricle or POA
      increased plasma LH concentrations in estrogen-primed ovariectomized rats.
      Metastin neurons were immunohistochemically found in the arcuate nucleus (ARC) to
      be colocalized with estrogen receptors with some fibers in the preoptic area
      (POA) in close apposition with GnRH neuronal cell bodies or fibers. Quantitative
      RT-PCR has revealed that KiSS-1 and GPR54 mRNAs were expressed in the ARC and
      POA, respectively. The blockade of local metastin action in the POA with a
      specific monoclonal antibody to rat metastin completely abolished proestrous LH
      surge and inhibited estrous cyclicity. Metastin-immunoreactive cell bodies in the
      ARC showed a marked increase and c-Fos expression in the early proestrus
      afternoon compared with the day of diestrus. Thus, metastin released in the POA
      is involved in inducing the preovulatory LH surge and regulating estrous
      cyclicity.

PMID- 15976059
TI  - Topical thyroid hormone accelerates wound healing in mice.
AB  - Although the physiologic role of thyroid hormone in skin is not well understood,
      mounting evidence suggests that T3 plays an important role in epidermal
      proliferation. The goal of this project was to evaluate whether the topical
      application of supraphysiologic doses of T3 could accelerate wound healing. We
      evaluated mice treated with topical T3 vs. the same mice receiving vehicle alone
      (Novasome A). Ten-millimeter diameter (79 mm2) dorsal skin wounds were
      established in all animals, and wounds were remeasured 4 d after injury. All
      animals were evaluated twice: once with the T3 treatment and once with the
      vehicle alone. Daily topical application of 150 ng T3 resulted in 58% greater
      wound closure relative to wounds on the same animals receiving vehicle alone (P <
      0.001). Furthermore, we determined that wound healing-associated keratin 6
      protein expression in hair follicle keratinocytes increased in a dose-dependent
      manner in vivo during topical T3 treatment. The data support our previous
      hypothesis that T3 is necessary for optimal wound healing. Now, we further
      suggest that topical thyroid hormone may be an inexpensive agent to hasten
      healing of certain wounds.

PMID- 15976060
TI  - Creation of estrogen resistance in vivo by transgenic overexpression of the
      heterogeneous nuclear ribonucleoprotein-related estrogen response element binding
      protein.
AB  - Estrogen unresponsiveness among primate species can result from overexpression of
      a heterogeneous nuclear ribonucleoprotein (hnRNP) that competes with estrogen
      receptor (ER) for binding to the estrogen-response element (ERE). This hnRNP has
      been coined the "ERE-binding protein" (ERE-BP). The ERE-BP is a member of the
      hnRNP C-like subfamily of hnRNPs, traditionally considered to be single-strand
      RNA binding proteins designed for the stabilization and handling of pre-mRNA. To
      verify in vivo the dominant-negative actions of the ERE-BP to inhibit ER-ERE
      directed transactivation and to avoid the potential for lethality from global
      overexpression of an hnRNP, we generated transgenic mice that overexpressed ERE
      BP in breast tissue under the control of a whey acidic protein gene promoter.
      Graded overexpression of ERE-BP in transgenic mice was established. Founders were
      viable and fertile. Female transgenics in all lines gave birth to pups, but their
      ability to nurse was dependent on the level of ERE-BP expression in breast; high
      ERE-BP expressors were unable to lactate. A gradient of impaired breast
      pheno(histo)type, from near normal to failed ductal development and lactational
      capacity, correlated with the relative level of transgene expression. ERE-BP,
      expressed either endogenously as a transgene or after transfection, colocalized
      with ERalpha in the nucleus of target cells. This work confirms that tissue
      targeted overexpression of the ERE-BP can effectively block estrogen-ERalpha-ERE
      directed action in vivo.

PMID- 15976061
TI  - Neuromedin s is a novel anorexigenic hormone.
AB  - A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been
      identified in rat brain and has been shown to be an endogenous ligand for two
      orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors
      have been identified as neuromedin U (NMU) receptor type 1 and type 2,
      respectively. In this study, the physiological role of the novel peptide, NMS, on
      feeding regulation was investigated. Intracerebroventricular (icv) injection of
      NMS decreased 12-h food intake during the dark period in rats. This anorexigenic
      effect was more potent and persistent than that observed with the same dose of
      NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was
      counteracted by coadministration of NMS. Icv administration of NMS increased
      proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in
      the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for
      alpha-MSH) and alpha-helical corticotropin-releasing factor-(9-41) (antagonist
      for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv
      injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc.
      When neuronal multiple unit activity was recorded in the PVN before and after icv
      injection of NMS, a significant increase in firing rate was observed 5 min after
      administration, and this increase continued for 100 min. These results suggest
      that the novel peptide, NMS, may be a potent anorexigenic hormone in the
      hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH
      mRNA in the PVN may be involved in NMS action on feeding.

PMID- 15976062
TI  - Orexin A modulates mitral cell activity in the rat olfactory bulb: patch-clamp
      study on slices and immunocytochemical localization of orexin receptors.
AB  - Orexin A and B are involved in feeding behaviors, and recently fibers containing
      these peptides were found in the rat olfactory bulb. These fibers, which
      originate from the lateral and posterior hypothalamus and the perifornical area,
      are distributed in the glomerular, mitral cell, and granule cell layers. Orexin
      receptors are mainly expressed by mitral cells. In the present study, RT-PCR
      experiments were done to determine orexin receptor expression during the early
      postnatal life of rats, and immunocytochemical experiments were performed to
      further clarify the structural and ultrastructural localization of orexin
      receptors in the olfactory bulb. Furthermore, a functional electrophysiological
      approach examined the action of orexin A on mitral cell excitability and
      spontaneous activity using in vitro patch-clamp techniques. RT-PCR results show
      that mRNA of the two type receptors, type 1 orexin receptors and type 2 orexin
      receptors, are expressed in the olfactory bulb of rat from 10 d to the adult
      stage. At the same ages, immunocytochemical data show that orexin 1 receptors are
      localized in the cell bodies of periglomerular, mitral/tufted, and granule cells.
      Immunoreactivity was also demonstrated in mitral/tufted cell dendrites arborizing
      in the glomerulus and mitral/tufted and granule cell processes running in the
      external plexiform layer. Functionally, orexin A produced either a direct,
      tetrodotoxin-insensitive depolarization in one group of mitral cells (7%), or, in
      another group (30%), an indirect, tetrodotoxin-sensitive hyperpolarization. Both
      actions were mediated by type 1 orexin receptors because the response was
      antagonized by SB-334867-A, a selective antagonist. Mitral cell recordings
      performed under bicuculline [gamma-aminobutyric acid (GABA)A receptor
      antagonist], indicate that the orexin-induced indirect hyperpolarization was
      partly mediated through GABA(A) receptors. Because granule cells and
      periglomerular cells express orexin receptors and are GABAergic cells, they could
      be both involved in this hyperpolarization. Other mechanisms, which could support
      an indirect hyperpolarization of mitral cells through dopamine interneuron
      solicitation, are proposed. Our results provide data that should allow us to
      better understand neural communication and regulation mechanisms between the
      hypothalamic feeding centers and the olfactory bulb.

PMID- 15976063
TI  - Evaluation and management of prostate-specific antigen recurrence after radical
      prostatectomy for localized prostate cancer.
AB  - A radical prostatectomy has been established as one of the standard management
      options for localized prostate cancer. However, a substantial proportion of
      patients who undergo a radical prostatectomy develop prostate-specific antigen
      (PSA) recurrence which is commonly defined as a PSA cut-off point value of 0.2
      ng/ml. Although the management of PSA recurrence after radical prostatectomy may
      depend on the site of recurrence, it is quite difficult to identify the recurrent
      lesion accurately based on the currently available imaging technology. Patients
      who have surgical margin involvement or a Gleason score < or =7 based on the
      radical prostatectomy specimens, who do not have nodal or seminal vesicle
      involvement, and who develop a PSA recurrence >1-2 years after surgery with a
      doubling time of >1 year, and whose pre-treatment PSA is < 1.0-1.5 ng/ml are
      considered to benefit from local treatment with at least 64 Gy of salvage
      radiotherapy. Patients with different characteristics are considered to have
      distant metastases or both local lesions and distant metastases, and thus may be
      candidates for hormonal manipulation rather than radiotherapy. Since local
      recurrent lesions are considered to be quite small at the early stage of PSA
      recurrence, hormonal manipulation may be sufficient to prevent disease
      progression instead of radiotherapy. However, the optimal type and timing of
      hormonal manipulation remain to be elucidated. As a result, no consensus
      regarding the treatment for PSA recurrence after radical prostatectomy has yet
      been reached.

PMID- 15976064
TI  - Long-term functional outcome and late complications of Studer's ileal neobladder.
AB  - OBJECTIVE: The purpose of this study was to evaluate the long-term functional
      outcome and late complications of Studer's ileal neobladder. METHODS: The study
      included 57 patients who underwent radical cystectomy and bladder reconstruction
      with Studer's ileal neobladder, and were followed-up for at least 3 months after
      surgery. The voiding and storage function, and late complications were evaluated.
      The times of evaluation after surgery were categorized into periods I (3-23
      months), II (24-59 months), III (60-95 months) and IV (> or =96 months). RESULTS:
      Daytime and night-time continence rates were 95.6 and 88.6%, respectively. The
      averages of functional capacity (439 ml), maximum flow rate (15.7 ml/s) and
      residual urine (35 ml) evaluated in period I were maintained in period IV. Of the
      57 patients, intermittent self-catheterization was needed in five (8.8%) due to
      incomplete emptying or urinary retention. Urethroileal anastomotic stricture was
      found in two patients (3.5%), who were successfully treated by transurethral
      intervention. Inguinal hernia was found in seven patients (12.8%), five of whom
      developed it within 2 years after surgery. CONCLUSIONS: Our results indicate that
      Studer's ileal neobladder had a favorable long-term functional outcome. Although
      late complication rates were low, the incidence of inguinal hernia was relatively
      high, and this was considered as a definite late complication in our study.

PMID- 15976065
TI  - Long-term outcome of a low-dose intravesical bacillus Calmette-Guerin therapy for
      carcinoma in situ of the bladder: results after six successive instillations of
      40 mg BCG.
AB  - BACKGROUND: In Japan, bacillus Calmette-Guerin (BCG: Tokyo 172 strain)
      instillation is generally performed at a dose of 80 mg once weekly for eight
      consecutive weeks; however, many adverse effects including severe ones have been
      reported. We employed a dose of 40 mg once a week for six consecutive weeks in
      principle for carcinoma in situ (CIS) of the bladder, and retrospectively
      evaluated its effectiveness and safety. METHODS: A total of 43 patients with CIS
      of the bladder were treated by this method and followed-up for a subsequent 12-79
      months (median, 54 months). The patients consisted of 35 males and eight females
      aged 45-87 years (mean, 67.5 years). Intravesical BCG instillation at a dose of
      40 mg was conducted once a week for six consecutive weeks. RESULTS: A complete
      response (CR) was achieved in 84% of the patients, in whom the recurrence-free
      rate was 72.4% after 3 years and 61.9% after 5 years. The median CR duration was
      37.5 months. Two patients underwent total cystectomy, but none died of bladder
      cancer. As adverse effects, bladder irritation symptoms were observed in 48.8%,
      pyuria in 46.5%, macroscopic hematuria in 18.6% and fever (>37.5 degrees C) in
      9.3%. There were no severe adverse effects requiring discontinuation of drug
      administration. CONCLUSION: Our present study corroborated both the effectiveness
      and safety of low-dose BCG therapy for CIS of the bladder. This therapy warrants
      further study by prospective randomized trials in the future.

PMID- 15976066
TI  - An evaluation of busulfan pharmacokinetics in patients undergoing hematopoietic
      stem cell transplantation.
AB  - BACKGROUND: Busulfan (BU) pharmacokinetics (PK) are shown to be highly variable
      and thus their evaluation is critical for the success of hematopoietic stem cell
      transplantation (HST) in Caucasians. However, there are no data available for
      Japanese patients. METHODS: BU PK were evaluated in seven Japanese adult patients
      who underwent allogeneic HST. Four patients received 16 doses of 1 mg/kg of oral
      BU every 6 h for over 4 days followed by 120 mg/kg of intravenous
      cyclophosphamide, while three patients were given eight doses of 1 mg/kg of oral
      BU over 2 days in addition to 180 mg/kg of intravenous fludarabine with or
      without 2 Gy of total body irradiation. Blood samples were collected for PK
      analysis after the sixth dose of BU was administered. RESULTS: The average plasma
      BU concentrations at steady state (Css) ranged from 745 to 2422 ng/ml. Four of
      seven patients had BU Css >1000 ng/ml, the previously defined concentration
      associated with an increased risk of regimen-related toxicity (RRT). Indeed, one
      of them developed hepatic veno-occlusive disease. On the other hand, no severe
      toxicity greater than grade II except stomatitis was observed in the remaining
      patients whose Css were <1000 ng/ml. CONCLUSION: A possible increased risk of RRT
      associated with high plasma BU concentrations should be kept in mind after oral
      administration of BU. A prospective trial of adjusting BU doses depending on the
      BU PK is warranted for Japanese patients.

PMID- 15976067
TI  - A new, accurate and conventional five-point method for quantitative evaluation of
      ascites using plain computed tomography in cancer patients.
AB  - BACKGROUND: To assess the exact response of the malignant ascites to the
      treatment, the objective measurement of the volume of ascites is essential. We
      have developed a simple method to measure the volume of ascites by using standard
      abdomino-pelvic computed tomography (CT). The aim of the study is to validate the
      accuracy of the measurements by comparing them with the standard volume
      calculation by using 3D-CT. METHODS: Twelve consecutive patients with cancer who
      had measurable ascites underwent 15 helical CT examinations. On conventional CT
      images, the thickness of ascites in centimeters was measured in three planes such
      as the bilateral subphrenic space (A and B), the bilateral paracolic space (C and
      D) and the pre-bladder space (E), and the average thickness: (A + B + C + D +
      E)/5 was then multiplied by the area of standard abdominal cavity in the anterior
      projection, that was assumed to be 1000 cm(2), to yield the volume of ascites: (A
      + B + C + D + E) x 200 (ml). The volume of ascites was compared with the exact
      volume, that was obtained from 3D-CT with the volume rendering method. RESULTS:
      The volume of ascites measured by the present method and the volume rendering
      method ranged from 140 to 4040 ml and from 86 to 4279 ml, respectively. The
      correlation was statistically significant with a correlation coefficient of 0.956
      (P < 0.01) using the Spearman's rank correlation. In 13 examinations with the
      exact volume > or =300 ml, the average ratio of the absolute difference in the
      volume was 12.9 +/- 13.9% as compared with 62.8 and 162.0% in two examinations
      with the exact volume < 300 ml. CONCLUSION: The preliminary study indicated that
      the present five-point method using a conventional CT was accurate in patients
      with the volume of ascites > or =300 ml. Because this procedure is simple and
      easy to perform, it should be feasible in many hospitals for the follow-up of
      ascites after treatment.

PMID- 15976068
TI  - Importance of the initial volume of parotid glands in xerostomia for patients
      with head and neck cancers treated with IMRT.
AB  - OBJECTIVE: Our aim was to evaluate predictors of xerostomia in patients with head
      and neck cancers treated with intensity-modulated radiation therapy (IMRT).
      METHODS: Thirty-three patients with pharyngeal cancer were evaluated for
      xerostomia after having been treated with IMRT. All patients were treated with
      whole-neck irradiation of 46-50 Gy by IMRT, followed by boost IMRT to the high
      risk clinical target volume to a total dose of 56-70 Gy in 28-35 fractions
      (median, 68 Gy). For boost IMRT, a second computed tomography (CT-2) scan was
      done in the third to fourth week of IMRT. Xerostomia was scored 3-4 months after
      the start of IMRT. RESULTS: The mean doses to the contralateral and ipsilateral
      parotid glands were 24.0 +/- 6.2 and 30.3 +/- 6.6 Gy, respectively. Among the 33
      patients, xerostomia of grades 0, 1, 2 and 3 was noted in one, 18, 12 and two
      patients, respectively. Although the mean dose to the parotid glands was not
      correlated with the grade of xerostomia, the initial volume of the parotid glands
      was correlated with the grade of xerostomia (P = 0.04). Of 17 patients with small
      parotid glands (< or =38.8 ml) on initial CT (CT-1), 11 (65%) showed grade 2 or
      grade 3 xerostomia, whereas only three (19%) of 16 patients with larger parotid
      glands showed grade 2 xerostomia (P < 0.05). The mean volume of the parotid
      glands on CT-1 was 43.1 +/- 15.2 ml, but decreased significantly to 32.0 +/- 11.4
      ml (74%) on CT-2 (P < 0.0001). CONCLUSIONS: Initial volumes of the parotid glands
      are significantly correlated with the grade of xerostomia in patients treated
      with IMRT. The volume of the parotid glands decreased significantly during the
      course of IMRT.

PMID- 15976069
TI  - Docetaxel + 5-fluorouracil + cisplatin 3-day combination chemotherapy as a first
      line treatment in patients with unresectable gastric cancer.
AB  - BACKGROUND: Our objective was to verify the efficacy and safety of "docetaxel + 5
      fluorouracil + cisplatin" 3-day combination chemotherapy as a first-line
      treatment in patients with unresectable gastric cancer. METHODS: Between January
      and November 2002, we enrolled 43 patients [males 31; median age 55 years (range
      24-74)] with inoperable gastric cancer who had not been seen previously in Seoul
      National University Hospital. The regimen used was docetaxel 70 mg/m(2) on day 1,
      cisplatin 40 mg/m(2) on days 2 and 3, and 5-fluorouracil 1200 mg/m(2) over 10 h
      on days 1-3, every 3 weeks. RESULTS: A total of 168 cycles were administered.
      Mean cycle number per patient was 3.9. The administered dose intensity of
      docetaxel was 21.23 mg/m(2)/week, 5-FU 1092.14 mg/m(2)/week and cisplatin 23.82
      mg/m(2)/week, which corresponded to 91.1, 91.0 and 89.5% of planned doses. Of the
      43 patients, response evaluation was possible in 40 and, of these patients, 17
      (42.5%) achieved a partial response, 13 (32.5%) stable disease, and 10 patients
      (25%) showed progressive disease. The median time to progression was 5.6 months
      [95% confidence interval (CI) 4.6-6.6 months]. Median overall survival was 9.0
      months. (95% CI 4.8-13.2 months). Leukopenia occurred during 21.4% of cycles (36
      of 168 cycles); 14.3% grade 1, 5.3% grade 2 and 1.8% grade 3. Anemia occurred in
      16.7% (28 of 168 cycles); 11.3% grade 1, 4.8% grade 2 and 0.6% grade 3.
      Thrombocytopenia was not observed. Diarrhea, stomatitis and hypersensitivity
      occurred in 4.7% (two out of 43 patients), respectively. Neutropenic fever
      occurred in two patients (4.7%) and myalgia in three (7.0%). CONCLUSION:
      "Docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy is an
      active and tolerable regimen as a first-line treatment in patients with
      unresectable gastric cancer.

PMID- 15976070
TI  - Successful treatment of pulmonary artery sarcoma by a two-drug combination
      chemotherapy consisting of ifosfamide and epirubicin.
AB  - We describe a case of 63-year-old woman with pulmonary artery sarcoma
      successfully treated with chemotherapy. She developed acute shortness of breath,
      and left chest and shoulder pain. Although a diagnosis of acute pulmonary
      embolism was made at a local hospital and she received anticoagulation and
      thrombolysis therapy, no improvement was achieved. Thereafter, she underwent a
      pulmonary thromboectomy in our hospital, and the histological diagnosis was
      intimal sarcoma of the pulmonary artery. Since post-operative computed tomography
      (CT) scans of the chest showed obvious persistence of an intraluminal
      hypoattenuated area in the left main pulmonary artery, the patient was treated
      with four cycles of a doublet chemotherapy consisting of ifosfamide (2.5
      g/m(2)/day) on days 1-5 and epirubicin (45 mg/m(2)/day) on days 2 and 3. CT scans
      of the chest after four cycles showed marked regression of the intraluminal
      hypoattenuated area in the left main pulmonary artery. This is the first case of
      pulmonary artery sarcoma responding to chemotherapy. Surgical resection is
      currently the most hopeful treatment for pulmonary artery sarcoma. However,
      intensive chemotherapy is worth trying in unresectable patients.

PMID- 15976071
TI  - Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
      (MALT lymphoma) in the thymus: report of four cases.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma in the thymus is extremely
      rare, and little is known about its clinicopathological features. In this study,
      we examined four cases of MALT lymphoma in the thymus at our institute in terms
      of clinicopathological features. Most patients had autoimmune disease or
      hyperglobulinemia, and they also had cysts in the tumors. Both elevated serum
      levels of autoantibodies and the polyclonal increase in serum Ig remained almost
      unchanged after total thymectomy in all patients. We recommend that MALT lymphoma
      in the thymus should be considered in the differential diagnosis when a cystic
      thymic mass is found and if the patient is Asian and/or has autoimmune disease or
      hyperglobulinemia.

PMID- 15976072
TI  - ACT: the Artemis Comparison Tool.
AB  - The Artemis Comparison Tool (ACT) allows an interactive visualisation of
      comparisons between complete genome sequences and associated annotations. The
      comparison data can be generated with several different programs; BLASTN, TBLASTX
      or Mummer comparisons between genomic DNA sequences, or orthologue tables
      generated by reciprocal FASTA comparison between protein sets. It is possible to
      identify regions of similarity, insertions and rearrangements at any level from
      the whole genome to base-pair differences. ACT uses Artemis components to display
      the sequences and so inherits powerful searching and analysis tools. ACT is part
      of the Artemis distribution and is similarly open source, written in Java and can
      run on any Java enabled platform, including UNIX, Macintosh and Windows.

PMID- 15976073
TI  - Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and
      retrieval of one-trial place memory.
AB  - Allocentric place memory may serve to specify the context of events stored in
      human episodic memory. Recently, our laboratory demonstrated that, analogous to
      event-place associations in episodic memory, rats could associate, within one
      trial, a specific food flavor with an allocentrically defined place in an open
      arena. Encoding, but not retrieval, of such flavor-place associations required
      hippocampal NMDA receptors; retrieval depended on hippocampal AMPA receptors.
      This might have partly reflected the contributions of these receptors to encoding
      and retrieval of one-trial place, rather than flavor-place, memory. Therefore,
      the present study developed a food-reinforced arena paradigm to study encoding
      and retrieval of one-trial allocentric place memory in rats; memory relied on
      visuospatial information and declined with increasing retention delay, still
      being significant after 6 h, the longest delay tested (experiments 1 and 2).
      Hippocampal infusion of the NMDA receptor antagonist d-AP-5 blocked encoding
      without affecting retrieval; hippocampal infusion of the AMPA receptor antagonist
      CNQX impaired retrieval (experiment 3). Finally, we confirmed that the d-AP-5
      infusions selectively blocked induction of long-term potentiation, a form of
      synaptic plasticity, whereas CNQX impaired fast excitatory transmission, at
      perforant-path dentate gyrus synapses in the dorsal hippocampus in vivo
      (experiment 4). Our results support that encoding, but not retrieval, of one
      trial allocentric place memory requires the NMDA receptor-dependent induction of
      hippocampal synaptic plasticity, whereas retrieval depends on AMPA receptor
      mediated fast excitatory hippocampal transmission. The contributions of
      hippocampal NMDA and AMPA receptors to one-trial allocentric place memory may be
      central to episodic memory and related episodic-like forms of memory in rats.

PMID- 15976074
TI  - Mash1 and Math3 are required for development of branchiomotor neurons and
      maintenance of neural progenitors.
AB  - Basic helix-loop-helix (bHLH) transcription factors are known to play important
      roles in neuronal determination and differentiation. However, their exact roles
      in neural development still remain to be determined because of the functional
      redundancy. Here, we examined the roles of neural bHLH genes Mash1 and Math3 in
      the development of trigeminal and facial branchiomotor neurons, which derive from
      rhombomeres 2-4. In Math3-null mutant mice, facial branchiomotor neurons are
      misspecified, and both trigeminal and facial branchiomotor neurons adopt abnormal
      migratory pathways. In Mash1;Math3 double-mutant mice, trigeminal and facial
      branchiomotor neurons are severely reduced in number partly because of increased
      apoptosis. In addition, neurons with migratory defects are intermingled over the
      midline from either side of the neural tube. Furthermore, oligodendrocyte
      progenitors of rhombomere 4 are reduced in number. In the absence of Mash1 and
      Math3, expression of Notch signaling components is severely downregulated in
      rhombomere 4 and neural progenitors are not properly maintained, which may lead
      to intermingling of neurons and a decrease in oligodendrocyte progenitors. These
      results indicate that Mash1 and Math3 not only promote branchiomotor neuron
      development but also regulate the subsequent oligodendrocyte development and the
      cytoarchitecture by maintaining neural progenitors through Notch signaling.

PMID- 15976075
TI  - Involvement of the central thalamus in the control of smooth pursuit eye
      movements.
AB  - During maintenance of smooth pursuit eye movements, the brain must keep track of
      pursuit velocity to reconstruct target velocity from motion of retinal images.
      Although a recent study showed that corollary discharge signals through the
      thalamus to the cortex are used for internal monitoring of saccades, it remains
      unknown whether signals in the thalamus also contribute to monitoring and on-line
      regulation of smooth pursuit. The present study sought possible roles of the
      thalamocortical pathways in pursuit by recording activities of single thalamic
      neurons and by analyzing the effects of local inactivation. Data showed that many
      neurons in the ventrolateral thalamus exhibited directional modulation during
      pursuit. Most neurons discharged before or during initiation of pursuit, and the
      firing rate was proportional to the speed of target motion in a preferred
      direction. When the tracking target was extinguished briefly during maintenance
      of pursuit, these neurons continued firing, indicating that they carried extra
      retinal, eye movement signals. The majority of neurons showed no change in
      activity around the time of small catch-up saccades during pursuit but responded
      transiently to large (16 degrees) memory-guided saccades in the preferred pursuit
      direction. Local inactivation of the recording sites did not alter pursuit
      latency but reduced eye velocity modestly during initiation and maintenance of
      ipsiversive pursuit. The results suggest that the central thalamus lies within
      pathways that regulate and monitor smooth pursuit eye movements.

PMID- 15976076
TI  - The nonpeptide calcitonin gene-related peptide receptor antagonist BIBN4096BS
      lowers the activity of neurons with meningeal input in the rat spinal trigeminal
      nucleus.
AB  - Calcitonin gene-related peptide (CGRP) has been suggested to play a major role in
      the pathogenesis of migraines and other primary headaches. CGRP may be involved
      in the control of neuronal activity in the spinal trigeminal nucleus (STN), which
      integrates nociceptive afferent inputs from trigeminal tissues, including
      intracranial afferents. The activity of STN neurons is thought to reflect the
      activity of central trigeminal nociceptive pathways causing facial pain and
      headaches in humans. In a rat model of meningeal nociception, single neuronal
      activity in the STN was recorded. All units had receptive fields located in the
      exposed parietal dura mater. Heat and cold stimuli were repetitively applied to
      the dura in a fixed pattern of ramps and steps. The nonpeptide CGRP receptor
      antagonist BIBN4096BS was topically applied onto the exposed dura or infused
      intravenously. BIBN4096BS (300 microg/kg, i.v.) reduced spontaneous activity by
      approximately 30%, the additional dose of 900 microg/kg intravenously by
      approximately 50% of the initial activity, whereas saline had no effect. The
      activity evoked by heat ramps was also reduced after BIBN4096BS (900 microg/kg,
      i.v.) by approximately 50%. Topical administration of BIBN4096BS (1 mm) did not
      significantly change the spontaneous neuronal activity within 15 min. We conclude
      that the endogenous release of CGRP significantly contributes to the maintenance
      of spontaneous activity in STN neurons. Blockade of CGRP receptors, possibly at
      central and peripheral sites, may therefore be an effective way to decrease
      nociceptive transmission. This may offer a new therapeutic strategy for the
      treatment of facial pain and primary headaches.

PMID- 15976077
TI  - Perceptual fusion and stimulus coincidence in the cross-modal integration of
      speech.
AB  - Human speech perception is profoundly influenced by vision. Watching a speaker's
      mouth movements significantly improves comprehension, both for normal listeners
      in noisy environments and especially for the hearing impaired. A number of brain
      regions have been implicated in audiovisual speech tasks, but little evidence
      distinguishes them functionally. In an event-related functional magnetic
      resonance imaging study, we differentiate neural systems that evaluate cross
      modal coincidence of the physical stimuli from those that mediate perceptual
      binding. Regions consistently involved in perceptual fusion per se included
      Heschl's gyrus, superior temporal sulcus, middle intraparietal sulcus, and
      inferior frontal gyrus. Successful fusion elicited activity biased toward the
      left hemisphere, although failed cross-modal binding recruited regions in both
      hemispheres. A broad network of other areas, including the superior colliculus,
      anterior insula, and anterior intraparietal sulcus, were more involved with
      evaluating the spatiotemporal correspondence of speech stimuli, regardless of a
      subject's perception. All of these showed greater activity to temporally offset
      stimuli than to audiovisually synchronous stimuli. Our results demonstrate how
      elements of the cross-modal speech integration network differ in their
      sensitivity to physical reality versus perceptual experience.

PMID- 15976078
TI  - Encoding and decoding of dendritic excitation during active states in pyramidal
      neurons.
AB  - Neocortical neurons spontaneously fire action potentials during active network
      states; how are dendritic synaptic inputs integrated into the ongoing action
      potential output pattern of neurons? Here, the efficacy of barrages of simulated
      EPSPs generated at known dendritic sites on the rate and pattern of ongoing
      action potential firing is determined using multisite whole-cell recording
      techniques from rat layer 5 neocortical pyramidal neurons in vitro. Under
      quiescent conditions, the somatic impact of proximal (253 +/- 15 microm from
      soma; n = 28) dendritic barrages of simulated EPSPs was 4.7-fold greater than
      identical barrages of EPSPs generated from distal (572 +/- 13 microm from soma)
      sites. In contrast, barrages of proximal simulated EPSPs enhanced the rate of
      ongoing action potential firing, evoked by somatic simulated EPSPs, by only 1.6
      fold more than distal simulated EPSPs. This relationship was apparent across a
      wide frequency range of action potential firing (6-22 Hz) and dendritic
      excitation (100-500 Hz). The efficacy of distal dendritic EPSPs was formed by the
      recruitment of active dendritic processes that transformed the ongoing action
      potential firing pattern, promoting action potential burst firing. Paired
      recordings (n = 42) revealed that patterns of action potential firing generated
      by concerted somatic and distal dendritic excitation reliably and powerfully
      drove postsynaptic excitation as a result of enhanced reliability of transmitter
      release during bursts of action potential firing. During active states,
      therefore, distal excitatory synaptic inputs decisively control the excitatory
      synaptic output of layer 5 neocortical pyramidal neurons and so powerfully
      influence network activity in the neocortex.

PMID- 15976079
TI  - Anesthetics change the excitation/inhibition balance that governs sensory
      processing in the cat superior colliculus.
AB  - The superior colliculus (SC) is a midbrain structure that plays a central role in
      the integration of information from different sensory modalities and the
      generation of orienting responses. Its normal function is thought to be governed
      by a strictly held balance between excitation and inhibition. This hypothesis was
      tested by recording from the same single units in the SC of cats before the
      injection of anesthetics, while anesthetics took effect, and after the injections
      during recovery. Sodium pentobarbital and ketamine, two agents commonly used in
      sensory physiology, were used. The results show a plethora of dose-dependent and
      nonlinear effects: the magnitude of evoked responses, receptive field properties,
      first spike latency, and bimodal integration were affected by both anesthetics in
      all units tested. Notably, prominent facilitation was observed at low levels of
      anesthesia, and inhibitory responses were changed into excitatory. Overall, the
      results challenge a fundamental tenet of sensory physiology: anesthesia, while
      decreasing single-unit responsiveness, leaves unaltered basic physiological
      properties.

PMID- 15976080
TI  - Three channels of corticothalamic communication during locomotion.
AB  - We studied the flow of corticothalamic (CT) information from the motor cortex of
      the cat during two types of locomotion: visually guided (cortex dependent) and
      unguided. Spike trains of CT neurons in layers V (CT5s) and VI (CT6s) were
      examined. All CT5s had fast-conducting axons (<2 ms conduction time), and nearly
      all showed step-phase-related activity (94%), sensory receptive fields (100%),
      and spontaneous activity (100%). In contrast, conduction times along CT6 axons
      were much slower, with bimodal peaks occurring at 6 and 32 ms. Remarkably, almost
      none of the slowest conducting CT6s showed step-related activity, sensory
      receptive fields, or spontaneous activity. As a group, these enigmatic neurons
      were all but silent. Some of the CT6s with moderately conducting axons showed
      step-related behavior (35%), and this response was more precisely timed than that
      of the CT5s. We propose distinct functional roles for these diverse
      corticothalamic populations.

PMID- 15976082
TI  - Sexual dimorphism of short-wavelength photoreceptors in the small white
      butterfly, Pieris rapae crucivora.
AB  - The eyes of the female small white butterfly, Pieris rapae crucivora, are
      furnished with three classes of short-wavelength photoreceptors, with sensitivity
      peaks in the ultraviolet (UV) (lambda(max) = 360 nm), violet (V) (lambda(max) =
      425 nm), and blue (B) (lambda(max) = 453 nm) wavelength range. Analyzing the
      spectral origin of the photoreceptors, we isolated three novel mRNAs encoding
      opsins corresponding to short-wavelength-absorbing visual pigments. We localized
      the opsin mRNAs in the retinal tissue and found that each of the short-wavelength
      sensitive photoreceptor classes exclusively expresses one of the opsin mRNAs. We,
      accordingly, termed the visual pigments PrUV, PrV, and PrB, respectively. The
      eyes of the male small white butterfly also use three classes of short-wavelength
      photoreceptors that equally uniquely express PrUV, PrV, and PrB. However, whereas
      the spectral sensitivities of the male photoreceptors with PrUV and PrB closely
      correspond to those of the female, the male photoreceptor expressing PrV has a
      double-peaked blue (dB) spectral sensitivity, strongly deviating from the
      spectral sensitivity of the female V photoreceptor. The male eyes contain a
      pigment that distinctly fluoresces under blue-violet as well as UV excitation
      light. It coexists with the dB photoreceptors and presumably acts as a spectral
      filter with an absorbance spectrum peaking at 416 nm. The narrow-band spectral
      sensitivity of the male dB photoreceptors probably evolved to improve the
      discrimination of the different wing colors of male and female P. rapae crucivora
      in the short-wavelength region of the spectrum.

PMID- 15976081
TI  - The role of thalamic inputs in surround receptive fields of barrel neurons.
AB  - Controversy exists regarding the relative roles of thalamic versus intracortical
      inputs in shaping the response properties of cortical neurons. In the whisker
      barrel system, this controversy centers on the mechanisms determining the
      receptive fields of layer IV (barrel) neurons. Whereas principal whisker-evoked
      responses are determined by thalamic inputs, the mechanisms responsible for
      adjacent whisker (AW) responses are in dispute. Here, we took advantage of the
      fact that lesions of the spinal trigeminal nucleus interpolaris (SpVi)
      significantly reduce the receptive field size of neurons in the ventroposterior
      thalamus. We reasoned that if AW responses are established by these thalamic
      inputs, brainstem lesions would significantly reduce the receptive field sizes of
      barrel neurons. We obtained extracellular single unit recordings from barrel
      neurons in response to whisker deflections from control rats and from rats that
      sustained SpVi lesions. After SpVi lesions, the receptive field of both
      excitatory and inhibitory barrel neurons decreased significantly in size, whereas
      offset/onset response ratios increased. Response magnitude decreased only for
      inhibitory neurons. All of these findings are consistent with the hypothesis that
      AW responses are determined primarily by direct thalamic inputs and not by
      intracortical interactions.

PMID- 15976083
TI  - Fasciclin II signals new synapse formation through amyloid precursor protein and
      the scaffolding protein dX11/Mint.
AB  - Cell adhesion molecules (CAMs) have been universally recognized for their
      essential roles during synapse remodeling. However, the downstream pathways
      activated by CAMs have remained mostly unknown. Here, we used the Drosophila
      larval neuromuscular junction to investigate the pathways activated by Fasciclin
      II (FasII), a transmembrane CAM of the Ig superfamily, during synapse remodeling.
      We show that the ability of FasII to stimulate or to prevent synapse formation
      depends on the symmetry of transmembrane FasII levels in the presynaptic and
      postsynaptic cell and requires the presence of the fly homolog of amyloid
      precursor protein (APPL). In turn, APPL is regulated by direct interactions with
      the PDZ (postsynaptic density-95/Discs large/zona occludens-1)-containing protein
      dX11/Mint/Lin-10, which also regulates synapse expansion downstream of FasII.
      These results provide a novel mechanism by which cell adhesion molecules are
      regulated and provide fresh insights into the normal operation of APP during
      synapse development.

PMID- 15976084
TI  - Long-term potentiation is impaired in middle-aged rats: regional specificity and
      reversal by adenosine receptor antagonists.
AB  - Memory loss in humans begins early in adult life and progresses thereafter. It is
      not known whether these losses reflect the failure of cellular processes that
      encode memory or disturbances in events that retrieve it. Here, we report that
      impairments in hippocampal long-term potentiation (LTP), a form of synaptic
      plasticity associated with memory, are present by middle age in rats but only in
      select portions of pyramidal cell dendritic trees. Specifically, LTP induced with
      theta-burst stimulation in basal dendrites of hippocampal field CA1 decayed
      rapidly in slices prepared from 7- to 10-month-old rats but not in slices from
      young adults. There were no evident age-related differences in LTP in the apical
      dendrites. Both the adenosine A1 receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine and a positive AMPA receptor modulator (ampakine) offset age
      related LTP deficits. Adenosine produced greater depression of synaptic responses
      in middle-aged versus young adult slices and in basal versus apical dendrites.
      These results were not associated with variations in A1 receptor densities and
      may instead reflect regional and age-related differences in adenosine clearance.
      Pertinent to this, brief applications of A1 receptor antagonists immediately
      after theta stimulation fully restored LTP in middle-aged rats. We hypothesize
      that the build-up of extracellular adenosine during theta activity persists into
      the postinduction period in the basal dendrites of middle-aged slices and thereby
      activates the A1 receptor-dependent LTP reversal effect. Regardless of the
      underlying mechanism, the present results provide a candidate explanation for
      memory losses during normal aging and indicate that, with regard to plasticity,
      different segments of pyramidal neurons age at different rates.

PMID- 15976085
TI  - Vocal pathways modulate efferent neurons to the inner ear and lateral line.
AB  - All sonic vertebrates face the problem of sound production interfering with their
      ability to detect and process external acoustic signals, including conspecific
      vocalizations. Direct efferent inputs to the inner ear of all vertebrates, and
      the lateral line system of some aquatic vertebrates, represent a potential
      mechanism to adjust peripheral sensitivity during sound production. We recorded
      from single efferent neurons that innervate the inner ear and lateral line in a
      sound-producing teleost fish while evoking fictive vocalizations predictive of
      the temporal features of natural vocalizations. The majority of efferent neurons
      showed an increase in activity that occurred in-phase with modulations in the
      fine temporal structure of the fictive vocalizations. Many of these neurons also
      showed a decrease in activity at fictive vocal offset. Efferents to the sacculus,
      the main auditory end organ, showed features especially well adapted for
      maintaining sensitivity to external acoustic signals during sound production.
      These included robust phase locking of efferent activity to each cycle of a
      fictive vocalization and a long-duration rebound suppression after each fictive
      vocalization that could provide a rapid, long-lasting period of sensitization to
      external acoustic stimuli such as the call of a conspecific. These results
      suggest that efferent activation by the vocal motor system can directly modulate
      auditory sensitivity to self-generated sounds and maintain sensitivity to ongoing
      external sounds. Given the conserved organization of the auditory efferent system
      across vertebrates, such mechanisms may be operative among all sonic vertebrates.

PMID- 15976086
TI  - Redundant localization mechanisms of RIM and ELKS in Caenorhabditis elegans.
AB  - Active zone proteins play a fundamental role in regulating neurotransmitter
      release and defining release sites. The functional roles of active zone
      components are beginning to be elucidated; however, the mechanisms of active zone
      protein localization are unknown. Studies have shown that glutamine, leucine,
      lysine, and serine-rich protein (ELKS), a recently defined member of the active
      zone complex, acts to localize the active zone protein Rab3a-interacting molecule
      (RIM) and regulates synaptic transmission in cultured neurons. Here, we test the
      function of ELKS in vivo. Like mammalian ELKS, Caenorhabditis elegans ELKS is an
      active zone protein that directly interacts with the postsynaptic density
      25/Discs large/zona occludens (PDZ) domain of RIM. However, RIM protein localizes
      in the absence of ELKS and vice versa. In addition, elks mutants exhibit neither
      the behavioral nor the physiological defects associated with unc-10 RIM mutants,
      indicating that ELKS is not a critical component of the C. elegans release
      machinery. Interestingly, expression of the soluble PDZ domain of RIM disrupts
      ELKS active zone targeting, suggesting a tight association between the two
      proteins in vivo. RIM truncations containing only the PDZ and C2A domains target
      to release sites in an ELKS-dependent manner. Together, these data identify ELKS
      as a new member of the C. elegans active zone complex, define the role of ELKS in
      synaptic transmission, and characterize the relationship between ELKS and RIM in
      vivo. Furthermore, they demonstrate that multiple different protein-protein
      interactions redundantly anchor both ELKS and RIM to active zones and implicate
      novel proteins in the formation of the active zone.

PMID- 15976087
TI  - The sensory cortical representation of the human penis: revisiting somatotopy in
      the male homunculus.
AB  - Pioneering mapping studies of the human cortex have established the notion of
      somatotopy in sensory representation, which transpired into Penfield and
      Rasmussen's famous sensory homunculus diagram. However, regarding the primary
      cortical representation of the genitals, classical and modern findings appear to
      be at odds with the principle of somatotopy, often assigning it to the cortex on
      the mesial wall. Using functional neuroimaging, we established a mediolateral
      sequence of somatosensory foot, penis, and lower abdominal wall representation on
      the contralateral postcentral gyrus in primary sensory cortex and a bilateral
      secondary somatosensory representation in the parietal operculum.

PMID- 15976088
TI  - Developmental changes in diffusion anisotropy coincide with immature
      oligodendrocyte progression and maturation of compound action potential.
AB  - Disruption of oligodendrocyte lineage progression is implicated in the white
      matter injury that occurs in cerebral palsy. We have previously published a model
      in rabbits consistent with cerebral palsy. Little is known of normal white-matter
      development in perinatal rabbits. Using a multidimensional approach, we defined
      the relationship of oligodendrocyte lineage progression and functional maturation
      of axons to structural development of selected cerebral white-matter tracts as
      determined by diffusion tensor imaging (DTI). Immunohistochemical studies showed
      that late oligodendrocyte progenitors appear at gestational age 22 [embryonic day
      22 (E22)], whereas immature oligodendrocytes appear at E25, and both increase
      rapidly with time (approximately 13 cells/mm2/d) until the onset of myelination.
      Myelination began at postnatal day 5 (P5) (E36) in the internal capsule (IC) and
      at P11 in the medial corpus callosum (CC), as determined by localization of
      sodium channels and myelin basic protein. DTI of the CC and IC showed that
      fractional anisotropy (FA) increased rapidly between E25 and P1 (E32) (11% per
      day) and plateaued (<5% per day) after the onset of myelination. Postnatal
      maturation of the compound action potential (CAP) showed a developmental pattern
      similar to FA, with a rapid rise between E29 and P5 (in the CC, 18% per day) and
      a slower rise from P5 to P11 (in the CC, <5% per day). The development of
      immature oligodendrocytes after E29 coincides with changes in FA and CAP area in
      both the CC and IC. These findings suggest that developmental expansion of
      immature oligodendrocytes during the premyelination period may be important in
      defining structural and functional maturation of the white matter.

PMID- 15976089
TI  - Noradrenaline transmission within the ventral bed nucleus of the stria terminalis
      is critical for fear behavior induced by trimethylthiazoline, a component of fox
      odor.
AB  - The bed nucleus of the stria terminalis (BNST) is involved in the mediation of
      fear behavior in rats. A previous study of our laboratory demonstrated that
      temporary inactivation of the BNST blocks fear behavior induced by exposure to
      trimethylthiazoline (TMT), a component of fox odor. The present study
      investigates whether noradrenaline release within the BNST is critical for TMT
      induced fear behavior. First, we confirmed previous studies showing that the
      ventral BNST is the part of the BNST that receives the densest noradrenaline
      innervation. Second, using in vivo microdialysis, we showed that noradrenaline
      release within the BNST is strongly increased during TMT exposure, and that this
      increase can be blocked by local infusions of the alpha2-receptor blocker
      clonidine. Third, using intracerebral injections, we showed that clonidine
      injections into the ventral BNST, but not into neighboring brain sites,
      completely blocked TMT-induced potentiation of freezing behavior. The present
      data clearly show that the noradrenergic innervation of the ventral BNST is
      important for the full expression of behavioral signs of fear to the predator
      odor TMT.

PMID- 15976090
TI  - Regulation of gene expression by chronic morphine and morphine withdrawal in the
      locus ceruleus and ventral tegmental area.
AB  - Morphine dependence is associated with long-term adaptive changes in the brain
      that involve gene expression. Different behavioral effects of morphine are
      mediated by different brain regions, for example, the locus ceruleus (LC), a
      noradrenergic nucleus, is implicated in physical dependence and withdrawal,
      whereas the ventral tegmental area (VTA), a dopaminergic nucleus, contributes to
      rewarding and locomotor responses to the drug. However, the global changes in
      gene expression that occur in these brain regions after morphine exposure and
      during withdrawal remain unknown. Using DNA microarray analysis in both mice and
      rats, we now characterize gene expression changes that occur in these brain
      regions with chronic morphine and antagonist-precipitated withdrawal. In the LC,
      numerous genes display common regulation between mouse and rat, including
      tyrosine hydroxylase, prodynorphin, and galanin. Furthermore, we identify
      clusters of genes that are regulated similarly by chronic morphine and by
      withdrawal, as well as clusters that show opposite regulation under these two
      conditions. Interestingly, most gene expression changes that occur in the VTA in
      response to chronic morphine are different from those seen in the LC, but the
      gene expression patterns in the two brain regions are very similar after
      withdrawal. In addition, we examined two genes (prodynorphin and FK506 binding
      protein 5) that are strongly regulated by chronic morphine or morphine withdrawal
      in the LC for their role in regulating withdrawal-associated behaviors.
      Inhibition of either protein profoundly affects withdrawal responses,
      demonstrating that the genes identified in this study have important functional
      roles in mediating opiate-induced behaviors.

PMID- 15976091
TI  - Intravesicular localization and exocytosis of alpha-synuclein and its aggregates.
AB  - Alpha-synuclein (alpha-syn), particularly in its aggregated forms, is implicated
      in the pathogenesis of Parkinson's disease and other related neurological
      disorders. However, the normal biology of alpha-syn and how it relates to the
      aggregation of the protein are not clearly understood. Because of the lack of the
      signal sequence and its predominant localization in the cytosol, alpha-syn is
      generally considered exclusively an intracellular protein. Contrary to this
      assumption, here, we show that a small percentage of newly synthesized alpha-syn
      is rapidly secreted from cells via unconventional, endoplasmic reticulum/Golgi
      independent exocytosis. Consistent with this finding, we also demonstrate that a
      portion of cellular alpha-syn is present in the lumen of vesicles. Importantly,
      the intravesicular alpha-syn is more prone to aggregation than the cytosolic
      protein, and aggregated forms of alpha-syn are also secreted from cells.
      Furthermore, secretion of both monomeric and aggregated alpha-syn is elevated in
      response to proteasomal and mitochondrial dysfunction, cellular defects that are
      associated with Parkinson's pathogenesis. Thus, intravesicular localization and
      secretion are part of normal life cycle of alpha-syn and might also contribute to
      pathological function of this protein.

PMID- 15976092
TI  - Propriospinal circuitry underlying interlimb coordination in mammalian
      quadrupedal locomotion.
AB  - Soon after birth, freely moving quadrupeds can express locomotor activity with
      coordinated forelimb and hindlimb movements. To investigate the neural mechanisms
      underlying this coordination, we used an isolated spinal cord preparation from
      neonatal rats. Under bath-applied 5-HT, N-methyl-d,l-aspartate (NMA), and
      dopamine (DA), the isolated cord generates fictive locomotion in which
      homolateral cervicolumbar extensor motor bursts occur in phase opposition, as
      does bursting in homologous (left-right) extensor motoneurons. This coordination
      corresponded to a walking gait monitored with EMG recordings in the freely
      behaving animal. Functional decoupling of the cervical and lumbar generators in
      vitro by sucrose blockade at the thoracic cord level revealed independent
      rhythmogenic capabilities with similar cycle frequencies in the two locomotor
      regions. When the cord was partitioned at different thoracic levels and 5
      HT/NMA/DA was applied to the more caudal compartment, the ability of the lumbar
      generators to drive their cervical counterparts increased with the proportion of
      chemically exposed thoracic segments. Blockade of synaptic inhibition at the
      lumbar level caused synchronous bilateral lumbar rhythmicity that, surprisingly,
      also was able to impose bilaterally synchronous bursting at the unblocked
      cervical level. Furthermore, after a midsagittal section from spinal segments C1
      to T7, and during additional blockade of cervical synaptic inhibition, the cord
      exposed to 5-HT/NMA/DA continued to produce a coordinated fictive walking pattern
      similar to that observed in control. Thus, in the newborn rat, a caudorostral
      propriospinal excitability gradient appears to mediate interlimb coordination,
      which relies more on asymmetric axial connectivity (both excitatory and
      inhibitory) between the lumbar and cervical generators than on differences in
      their inherent rhythmogenic capacities.

PMID- 15976093
TI  - Comprehensive antibody epitope mapping of the nucleocapsid protein of severe
      acute respiratory syndrome (SARS) coronavirus: insight into the humoral immunity
      of SARS.
AB  - BACKGROUND: The epidemic outbreak of severe acute respiratory syndrome (SARS)
      posed a worldwide threat to public health and economic stability. Although the
      pandemic has been contained, concerns over its recurrence remain. It is essential
      to identify specific diagnostic agents and antiviral vaccine candidates to fight
      this highly contagious disease. METHODS: We generated 14 monoclonal antibodies
      (mAbs) specific to the SARS coronavirus (SARS-CoV) nucleocapsid (N) protein and
      used these to thoroughly map the N protein antigenic determinants. We identified
      the immunodominant antigenic sites responsible for the antibodies in sera from
      SARS patients and antisera from small animals and differentiated the linear from
      the conformational antibody-combining sites comprising the natural epitopes by
      use of yeast surface display. RESULTS: We identified 5 conformational and 3
      linear epitopes within the entire N protein; 3 conformational and 3 linear
      epitopes were immunodominant. The antibody responses to the N protein fragments
      in mammalian sera revealed that 3 regions of the N protein are strong antigenic
      domains. We expanded the specificity of the N protein epitope and identified 4
      novel conformational epitopes (amino acids 1-69, 68-213, 212-341, and 337-422).
      CONCLUSION: The antigenic structures identified for the SARS-CoV N protein, the
      epitope-specific mAbs, and the serum antibody profile in SARS patients have
      potential use in the clinical diagnosis and understanding of the protective
      immunity to SARS-CoV.

PMID- 15976094
TI  - Novel changes in beta2-microglobulin in dialysis patients.

PMID- 15976095
TI  - Mass spectrometry for genotyping hepatitis C virus: a promising new approach.

PMID- 15976096
TI  - Evaluation of the quantitative analytical methods real-time PCR for HER-2 gene
      quantification and ELISA of serum HER-2 protein and comparison with fluorescence
      in situ hybridization and immunohistochemistry for determining HER-2 status in
      breast cancer patients.
AB  - BACKGROUND: HER-2 status is generally determined by immunohistochemistry (IHC) or
      fluorescence in situ hybridization (FISH). Both methods are only
      semiquantitative, require a tumor sample, and can be difficult to reproduce. We
      compared these methods with 2 quantitative approaches, one measuring HER-2 gene
      copy number in tissue by real-time quantitative PCR (qPCR), and the other
      measuring shed HER-2 protein in serum by ELISA in patients with metastatic
      disease. METHODS: We analyzed 52 cases of metastatic breast cancer for which both
      serum collected at the diagnosis of metastasis and stored primary breast tumor
      specimens were available. The within- and between-run imprecision of real-time
      qPCR and ELISA were evaluated according to Clinical and Laboratory Standards
      Institute (formerly known as NCCLS) recommendations. Concordance among the 4
      methods was assessed by calculating the kappa statistic and its 95% confidence
      interval (95% CI). RESULTS: The CVs for within- and between-run imprecision were
      both <10% with qPCR and ELISA. There was good agreement of results between qPCR
      and IHC (kappa = 0.81; 95% CI, 0.64-0.99), qPCR and FISH (kappa = 0.77; 95% CI,
      0.58-0.96), ELISA and IHC (kappa = 0.65; 95% CI, 0.41-0.89); and ELISA and FISH
      (kappa = 0.69; 95% CI, 0.46-0.92). CONCLUSIONS: Measurements of HER-2 gene
      expression by qPCR and of serum HER-2 protein by ELISA are highly reproducible
      approaches for determining HER-2 status in metastatic breast cancer. In addition,
      ELISA eliminates the need for biopsy.

PMID- 15976097
TI  - Multiplexed analysis of biomarkers related to obesity and the metabolic syndrome
      in human plasma, using the Luminex-100 system.
AB  - BACKGROUND: The complex pathology of disease has sparked the development of novel
      protein expression profiling techniques that require validation in clinical
      settings. This study focuses on multiplexed analyses of adipocytokines and
      biomarkers linked to the metabolic syndrome, diabetes, and cardiovascular
      disease. METHODS: Multiplexed immunoassays using fluorescent microspheres and the
      Luminex-100 system were performed on plasma from 80 obese patients (40 with the
      metabolic syndrome) before and after 6-8 weeks of diet-induced weight loss.
      Leptin, insulin, C-peptide, monocyte chemoattractant protein-1 (MCP-1), eotaxin,
      interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-6
      concentrations measured with multiplex panels from 3 different manufacturers were
      compared with results from commercial ELISAs. Detection limits and between- and
      within-run imprecision were determined for each analyte. Bland-Altman analysis
      was used to determine agreement between multiplexed immunoassays and ELISAs.
      RESULTS: Correlation between the Luminex multiplexed assays and ELISAs was good
      for leptin (Linco), insulin (Linco), MCP-1 (Biosource and Upstate), and eotaxin
      (Biosource) with correlation coefficients of 0.711-0.895; fair for eotaxin
      (Upstate) and C-peptide (Linco) with correlation coefficients of 0.496-0.582; and
      poor for TNF-alpha, IL-8, and IL-6 (Linco, Biosource, Upstate, and R&D) with
      correlation coefficients of -0.107 to 0.318. Within- and between-run imprecision
      values for the multiplex method were generally <15%. Relative changes in plasma
      leptin and insulin concentrations after diet-induced weight loss were similar
      whether assessed by multiplex assay or ELISA. CONCLUSION: Although this
      technology appears useful in clinical research studies, low assay sensitivity and
      poor correlations with conventional ELISA methods for some analytes with very low
      plasma concentrations should be considered when using the Luminex platform in
      clinical studies.

PMID- 15976098
TI  - Calibration curves for real-time PCR.
AB  - BACKGROUND: Despite the increasing use of real-time PCR in the diagnosis and
      management of viral infections, there are no published studies adequately
      addressing the optimum number of calibrators, the number of replicates of each
      calibrator, and the frequency with which calibration needs to be repeated. This
      study was designed to address these issues. METHODS: Cycle threshold data (ABI
      7700) was collected from >50 consecutive real-time PCR runs for hepatitis B and
      Epstein-Barr viruses. Our routine calibration curve made from serial 10-fold
      dilutions run in duplicate was compared with alternative options, including
      duplicate 100-fold dilutions, inclusion of a low-copy calibrator, and omission of
      the duplicate determination. Control data were used to examine the use of an
      average calibration curve made from multiple runs. RESULTS: Use of duplicate
      serial 10-fold dilutions led to the least imprecision, duplicate 100-fold
      dilutions had slightly higher imprecision, and calibration curves obtained with
      singlet measurements showed the greatest imprecision. For patient data, the
      duplicate 100-fold dilution calibration curve produced results that best matched
      those from the routine calibration curve. Use of singlet dilutions or inclusion
      of a low-copy calibrator produced poorer agreement. Variability in controls was
      lower with a daily calibration curve than with an average calibration curve.
      CONCLUSIONS: Duplicate 100-fold dilution calibration curves produced equivalent
      results and the same imprecision as curves with more calibrators, and thus are a
      valid alternative. Laboratories should carefully evaluate the variability
      resulting from the use of average calibration curves before adopting this
      approach.

PMID- 15976099
TI  - Postanalytical external quality assessment of blood glucose and hemoglobin A1c:
      an international survey.
AB  - BACKGROUND: Diabetes mellitus (DM) is diagnosed and monitored worldwide by blood
      glucose (BG) and glycohemoglobin A(1c) (HbA(1c)) testing, respectively. Methods
      for quality assessment of clinician interpretations of changes in these
      laboratory results have been developed. This study uses survey responses from
      general practitioners (GPs) in different countries to investigate possible
      differences in interpretation of results, as well as the feasibility of
      performing international postanalytical external quality assessment surveys (P
      EQAS). METHODS: GPs recruited from 7 countries received questionnaires requesting
      interpretation of changes in a potentially diagnostic capillary BG result and an
      HbA(1c) value obtained during monitoring of a patient with type 2 DM. GPs were
      asked to estimate clinically significant differences between 2 consecutive
      laboratory results [critical difference (CD)/reference change value] for both BG
      and HbA(1c). The CDs reported by GPs were used to calculate the analytical
      variation (CV(a)), which was taken as the quality specification for analytical
      imprecision. Participants received national benchmarking feedback reports after
      the survey. RESULTS: The study included responses from 2538 GPs. CDs in BG
      results showed the same pattern and were comparable among countries. Calculated
      median CV(a) values would be possible to attain at 80% confidence but not at the
      conventional 95% confidence. For HbA(1c), the same pattern was shown across
      countries, but with lower changes considered true when HbA(1c) increased than
      when it decreased. Despite the consistent pattern, variations among GPs were
      considerable in all countries. CONCLUSIONS: Assessments of CDs for BG and HbA(1c)
      were similar internationally, and quality specifications for these analytes based
      on clinicians' opinions are therefore interchangeable among countries.
      International P-EQAS may contribute to a more rational use of laboratory services
      and clinical guidelines.

PMID- 15976100
TI  - Iron stores, blood donation, and insulin sensitivity and secretion.
AB  - BACKGROUND: Epidemiologists have observed that blood donation is associated with
      decreased risk of type 2 diabetes and cardiovascular disease. METHODS: We
      investigated the relationship between iron stores and insulin sensitivity, after
      controlling for known confounding factors, and compared insulin sensitivity
      between blood donors and individuals who had never donated blood (nondonors). In
      181 men, insulin sensitivity and insulin secretion were evaluated through
      frequently sampled intravenous glucose tolerance tests with minimal model
      analysis. Men who donated blood between 6 months and 5 years before inclusion (n
      = 21) were carefully matched with nondonors (n = 66) for age, body mass index,
      waist-to-hip ratio, and cardiovascular risk profile, including blood lipids,
      blood pressure, and smoking status. RESULTS: Frequent blood donors (2-10
      donations) had increased insulin sensitivity [3.42 (1.03) vs 2.45 (1.2) x 10(-4)
      x min(-1) x mIU/L; P = 0.04], decreased insulin secretion [186 (82) vs 401.7
      (254) mIU/L x min; P <0.0001], and significantly lower iron stores [serum
      ferritin, 101.5 (74) vs 162 (100) microg/L; P = 0.017] than nondonors, but the 2
      groups had similar blood hematocrits and blood hemoglobin concentrations.
      CONCLUSIONS: Blood donation is simultaneously associated with increased insulin
      sensitivity and decreased iron stores. Stored iron seems to impact negatively on
      insulin action even in healthy people, and not just in classic pathologic
      conditions associated with iron overload (hemochromatosis and hemosiderosis).
      According to these observations, it is imperative that a definition of excessive
      iron stores in healthy people be formulated.

PMID- 15976101
TI  - Multianalyte quantification of vitamin B6 and B2 species in the nanomolar range
      in human plasma by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Homocysteine, a risk factor of cardiovascular disease, cognitive
      disorders, and pregnancy complications, exists at a point of metabolic
      convergence of several B vitamins, including vitamins B(6) and B(2) (riboflavin).
      Measurement of the various forms of these vitamins may be useful for the study of
      hyperhomocysteinemia as well as for the assessment of vitamin status. METHODS:
      Plasma (60 microL) was deproteinized by mixing with an equal volume of 50 g/L
      trichloroacetic acid that contained d(2)-pyridoxal 5'-phosphate, d(3)-pyridoxal,
      and d(8)-riboflavin as internal standards. Pyridoxal (PL), pyridoxal 5'-phosphate
      (PLP), pyridoxine (PN), pyridoxine 5'-phosphate, pyridoxamine (PM), pyridoxamine
      5'-phosphate, 4-pyridoxic acid (PA), riboflavin, flavin mononucleotide (FMN), and
      FAD were separated on a C(8) reversed-phase column, which was developed with an
      acetonitrile gradient in a buffer containing acetic acid and heptafluorobutyric
      acid. The analytes were detected by tandem mass spectrometry in the positive-ion
      mode. RESULTS: The chromatographic run lasted 8 min. Within- and between-day CVs
      were 3%-20% and 6%-22%, respectively, and recoveries were 78%-163%. Limits of
      detection (signal-to-noise ratio = 5) were in the range 0.1-4.0 nmol/L, and the
      response was linear over several orders of magnitude. In samples from 94 healthy
      persons, we obtained median concentrations (nmol/L) of 35.4 for PLP, 16.9 for PL,
      22.4 for PA, 10.3 for riboflavin, 7.5 for FMN, and 63.1 for FAD. PN and PM were
      also detected in some cardiovascular patients taking B(6) supplements.
      CONCLUSIONS: This method based on liquid chromatography-tandem mass spectrometry
      measures all known plasma forms of vitamins B(6) and B(2), which span a wide
      range of polarity. The assay is characterized by simple sample processing with no
      derivatization, low sample volume requirement, and a short run time.

PMID- 15976102
TI  - High-throughput purification of viral RNA based on novel aqueous chemistry for
      nucleic acid isolation.
AB  - BACKGROUND: Extraction protocols using magnetic solid phases offer a high
      potential for automation. However, commercially available magnetic-bead-based
      assays either lack the sensitivity required for viral diagnostics or are
      disproportionately expensive. METHODS: We developed an aqueous chemistry for
      extraction of viral nucleic acids from plasma samples by use of common magnetic
      silica beads. Nucleic acids were bound to the beads at acidic conditions in the
      presence of a kosmotropic salt and were eluted at a slightly alkaline pH. The
      method was implemented on a standard pipetting workstation for fully automated
      extraction of up to 48 samples of 240 muL plasma in 1 batch. RESULTS: The
      detection limit of the method was comparable to the spin-column-based QIAamp
      Viral RNA Mini Kit, which relies on chaotropic salts and binding to a silica
      membrane, as the comparison method. The 95% detection limit was 23.1 IU per PCR
      for HIV-1 and 10.7 IU per PCR for hepatitis C virus (HCV). Suitability for
      clinical routine testing was confirmed in a total of 178 HIV-1- or HCV-positive
      plasma samples. The method linearity (R(2)) was >0.99 for the viruses evaluated.
      CONCLUSIONS: Use of reagents without organic solvents allows simple and cost
      effective automation of this method on common pipetting robots with low risk of
      contamination. Performance characteristics of the novel extraction method make it
      suitable for use in diagnosis of infectious diseases and viral load
      determinations.

PMID- 15976103
TI  - Collection and storage of human blood cells for mRNA expression profiling: a 15
      month stability study.

PMID- 15976104
TI  - Denaturing HPLC coupled with multiplex PCR for rapid detection of large deletions
      in Duchenne muscular dystrophy carriers.

PMID- 15976105
TI  - Congenital analbuminemia attributable to compound heterozygosity for novel
      mutations in the albumin gene.

PMID- 15976106
TI  - Circulating ghrelin in patients undergoing elective cholecystectomy.

PMID- 15976107
TI  - Double-gradient-denaturing-gradient gel electrophoresis for mutation screening of
      the BCR-ABL tyrosine kinase domain in chronic myeloid leukemia patients.

PMID- 15976108
TI  - Relationship between serum folate and plasma nitrate concentrations: possible
      clinical implications.

PMID- 15976109
TI  - Liquid chromatography-tandem mass spectrometry method for the analysis of
      asymmetric dimethylarginine in human plasma.

PMID- 15976110
TI  - Relationship between isoprostane concentrations, metabolic acidosis, and morbid
      neonatal outcome.

PMID- 15976111
TI  - Comparison of a fully automated immunoassay with a point-of-care testing method
      for B-type natriuretic peptide.

PMID- 15976112
TI  - Invasive trophoblast antigen (hyperglycosylated human chorionic gonadotropin) as
      a first-trimester serum marker for Down syndrome.

PMID- 15976113
TI  - Validating a rapid method for detecting common polymorphisms in the APOA5 gene by
      melting curve analysis using LightTyper.

PMID- 15976114
TI  - Two-step genetic screening of thrombophilia by pyrosequencing.

PMID- 15976115
TI  - Arrayed primer extension resequencing of mutations in the TP53 tumor suppressor
      gene: comparison with denaturing HPLC and direct sequencing.

PMID- 15976116
TI  - Rapid, simultaneous genotyping of 10 Southeast Asian glucose-6-phosphate
      dehydrogenase deficiency-causing mutations and a silent polymorphism by multiplex
      primer extension/denaturing HPLC assay.

PMID- 15976117
TI  - Inadequate attempts to measure the microheterogeneity of transthyretin by low
      resolution mass spectrometry.

PMID- 15976120
TI  - Validation of a multiplex PCR assay for the simultaneous detection of human
      papillomavirus and Chlamydia trachomatis in cervical PreservCyt samples.

PMID- 15976121
TI  - Detection of heavy chain disease by capillary zone electrophoresis.

PMID- 15976122
TI  - Identification of hemoglobin variants by HPLC.

PMID- 15976123
TI  - Limited additional release of cardiac troponin I and T in isoproterenol-treated
      beagle dogs with cardiac injury.

PMID- 15976125
TI  - Quality specifications for imprecision of B-type natriuretic peptide assays.

PMID- 15976127
TI  - Analysis of mass spectrometry profiles of the serum proteome.

PMID- 15976128
TI  - Performance of clinical laboratories for DNA analyses to detect thrombophilia
      mutations.

PMID- 15976129
TI  - Hypertriglyceridemia: interaction between APOE and APOAV variants.

PMID- 15976130
TI  - Reason for limitations of heterophilic blocking tube use on certain beckman
      coulter access assays.

PMID- 15976131
TI  - Mutations in K-ras codon 12 detected in plasma DNA are not an indicator of
      disease in patients with non-small cell lung cancer.

PMID- 15976132
TI  - Denaturing HPLC-based assay for detection of ATRX gene mutations.

PMID- 15976133
TI  - Whole-blood hypercholinemia and coronary instability and thrombosis.

PMID- 15976134
TI  - Circulating nucleic acids in blood of healthy male and female donors.

PMID- 15976136
TI  - Obesity in Spanish schoolchildren: relationship with lipid profile and insulin
      resistance.
AB  - This article reports cross-sectional data from a total of 1048 children, 6 to 8
      years of age, categorized by presence or absence of obesity, who participated in
      a voluntary survey of cardiovascular risk factors in Spain over the period of
      1998 to 2000, to establish the relationship between obesity and its metabolic
      consequences at this age. The prevalence of obesity and overweight were 9.4% and
      15.7%, respectively, in boys and 10.5% and 18.0%, respectively, in girls. We
      observed that, in both sexes, obese children had higher triglycerides and lower
      high-density lipoprotein-cholesterol levels than non-obese children. No
      differences were found in plasma glucose or low-density lipoprotein-cholesterol
      levels between normal and obese children. However, we observed that insulin
      levels and the homeostasis model assessment for insulin resistance were
      significantly (p<0.001) higher in obese children of both sexes but that free
      fatty acid levels were lower in obese children than in nonobese children, with a
      statistical significance in girls (0.72+/-0.30 vs. 0.61+/-0.16 mEq/liter). In
      summary, our survey found some metabolic consequences of obesity similar to those
      found in adults (elevated triglycerides, insulin, and the homeostasis model
      assessment for insulin resistance, and lower high-density lipoprotein
      cholesterol). However, other features (glucose, total cholesterol, low-density
      lipoprotein-cholesterol, and free fatty acid levels) were found to behave
      differently, indicating that the association of obesity with risk factors seems
      to change as the children age and may depend on the chronology of sexual
      maturation.

PMID- 15976135
TI  - Novel variants in the putative peroxisome proliferator-activated receptor {gamma}
      promoter and relationships with obesity in men.
AB  - Yet unidentified variants within the peroxisome proliferator-activated receptor
      gamma (PPARgamma) 2 promoter may explain the inconsistent reports on associations
      between variants in the coding region and obesity or diabetes. Thus, we examined
      the putative PPARgamma2 promoter (-3371 to +43 bp) for variants in 83 subjects
      with obesity or type 2 diabetes. We identified eight variants, seven of which
      were novel, including -792A>G, -816C>T, -882T>C, -1505G>A, -1881C>T, -1884T>A, 
      2604T>C, and -2953A>G. The variants -816C>T, -1505G>A, -1881C>T, and -2604T>C
      were in total linkage disequilibrium, and there was a high degree of linkage
      disequilibrium between several of the novel variants and Pro12Ala. The novel
      variants were, together with Pro12Ala and 1431C>T, examined for relationships
      with obesity among 234 men with early-onset obesity with a BMI at age
      approximately 20 years of 33.2+/-2.5 kg/m2 and 323 nonobese men with a BMI of
      21.7+/-2.5 kg/m2, who were also reexamined after approximately 29 years. The
      prevalence of the identified variants was not significantly different between the
      two groups, and the variants did not affect changes in BMI over time. In
      conclusion, the identified novel variants in the PPARgamma2 promoter region do
      not explain the reported discrepancies in the association of previously
      identified variants with obesity and type 2 diabetes.

PMID- 15976137
TI  - Obesity and overweight prevalence in Polish 7- to 9-year-old children.
AB  - OBJECTIVE: Secular trend in childhood obesity is a well-known phenomenon, and it
      is important to monitor it in cross-sectional studies. The study aim was to
      estimate prevalence of obesity and overweight in Polish 7- to 9-year-old children
      and to compare the results with a French study based on the same protocol.
      RESEARCH METHODS AND PROCEDURES: The study was conducted in 2001 according to the
      protocol of the European Childhood Obesity Group. Height and weight were
      measured, and BMI was calculated to define nutritional status in a randomly
      selected group of 2916 (1445 girls and 1471 boys) primary school children.
      Obesity and overweight were estimated according to International Obesity Task
      Force references with curve for obesity and overweight passing through 30 and 25
      kg/m(2) at age 18, respectively. RESULTS: Overweight (including obesity) was
      found in 15.4% of Polish children (in 15.8% of girls and 15.0% of boys) and
      obesity in 3.6% (3.7% of girls and 3.6% of boys) compared with 18.1% of
      overweight and 3.8% of obese children in French study. There was no significant
      difference in nutrition status between Polish and French children except for
      higher frequency of overweight in French 9-year-old boys. The same trend of
      decreasing overweight through age classes was observed in both populations.
      DISCUSSION: The prevalence of obesity and overweight (including obesity) in
      prepubertal children estimated in two European countries according to the same
      protocol and using the same references showed little differences between the two
      populations despite higher prevalence of obesity in Polish than French adults.

PMID- 15976138
TI  - Angiotensin II promotes leptin production in cultured human fat cells by an
      ERK1/2-dependent pathway.
AB  - OBJECTIVE: The fat cell hormone leptin is known to be implicated in the
      pathogenesis of hypertension and cardiovascular disease. Here we tested whether
      angiotensin (Ang) II is involved in the control of leptin release from human
      adipocytes. RESEARCH METHODS AND PROCEDURES: Leptin secretion was assessed from
      in vitro differentiated human adipocytes by radioimmunoassay. Western blot
      experiments were used to test for the signaling pathway activated by Ang II.
      RESULTS: Ang II increased leptin secretion into the culture medium in a dose- and
      time-dependent fashion. At 10(-5) M Ang II, the leptin concentration in the
      medium was increased at 24 hours by 500+/-222% compared with control cultures
      (p<0.05). This effect was also seen at the mRNA level. Similar effects were seen
      after exposure of fat cells to Ang III and Ang IV. Preincubation of fat cells
      with candesartan, an angiotensin II type 1 receptor antagonist, or the
      extracellular-signal-regulated kinases 1 and 2 inhibitor UO126 completely
      abolished the effect of Ang II on leptin production. The peroxisome proliferator
      activated receptor-gamma agonist troglitazone modestly attenuated leptin release.
      DISCUSSION: In conclusion, Ang II and its metabolites stimulated leptin
      production in human adipocytes. This effect is mediated through an extracellular
      signal-regulated kinases 1 and 2-dependent pathway and includes the angiotensin
      II type 1 receptor subtype.

PMID- 15976139
TI  - Extracellular cyclic AMP-adenosine pathway in isolated adipocytes and adipose
      tissue.
AB  - OBJECTIVE: Our goal was to evaluate the presence and lipolytic impact of the
      extracellular cyclic adenosine monophosphate (AMP)-adenosine pathway in adipose
      tissue. RESEARCH METHODS AND PROCEDURES: Sixteen miniature Yucatan swine (Sus
      scrofa) were used for these in vitro and in situ experiments. Four microdialysis
      probes were implanted into subcutaneous adipose tissue and perfused at 2
      microL/min with Ringer's solution containing no addition, varying levels of
      cyclic AMP, 10 microM isoproterenol, or 10 microM isoproterenol plus 1 mM
      alpha,beta-methylene adenosine 5'-diphosphate (AMPCP), a 5'-nucleotidase
      inhibitor. Dialysate was assayed for AMP, adenosine, inosine, hypoxanthine, and
      glycerol. Freshly isolated adipocytes were incubated with buffer, 1 microM
      isoproterenol, or 1 microM isoproterenol plus 0.1 mM AMPCP, and extracellular
      levels of AMP, adenosine, inosine, hypoxanthine, and glycerol were measured.
      RESULTS: Perfusion of adipose tissue with exogenous cyclic AMP caused a
      significant increase in AMP and adenosine appearance. Perfusion with AMPCP, in
      the presence or absence of isoproterenol, significantly increased the levels of
      AMP and glycerol, whereas it significantly reduced the level of adenosine and its
      metabolites. However, the AMPCP-provoked increase in lipolysis observed in situ
      and in vitro was not temporally associated with a decrease in adenosine.
      DISCUSSION: These data suggest the existence of a cyclic AMP-adenosine pathway in
      adipocytes and adipose tissue. The role of this pathway in the regulation of
      lipolysis remains to be clarified.

PMID- 15976140
TI  - Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces
      apoptosis in 3T3-L1 adipocytes.
AB  - OBJECTIVE: Green tea catechins have been shown to promote loss of body fat and to
      inhibit growth of many cancer cell types by inducing apoptosis. The objective of
      this study was to determine whether epigallocatechin gallate (EGCG), the primary
      green tea catechin, could act directly on adipocytes to inhibit adipogenesis and
      induce apoptosis. RESEARCH METHODS AND PROCEDURES: Mouse 3T3-L1 preadipocytes and
      mature adipocytes were used. To test the effect of EGCG on viability, cells were
      incubated for 3, 6, 12, or 24 hours with 0, 50, 100, or 200 microM EGCG.
      Viability was quantitated by MTS assay. To determine the effect of EGCG on
      apoptosis, adipocytes were incubated for 24 hours with 0 to 200 microM EGCG, then
      stained with annexin V and propidium iodide and analyzed by laser scanning
      cytometry. Both preadipocytes and adipocytes were also analyzed for apoptosis by
      terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. To determine
      the effect of EGCG on adipogenesis, maturing preadipocytes were incubated during
      the 6-day induction period with 0 to 200 microM EGCG, then stained with Oil-Red-O
      and analyzed for lipid content. RESULTS: EGCG had no effect on either viability
      or apoptosis of preconfluent preadipocytes. EGCG also did not affect viability of
      mature adipocytes; however, EGCG increased apoptosis in mature adipocytes, as
      demonstrated by both laser scanning cytometry and terminal deoxynucleotidyl
      transferase dUTP nick-end labeling assays. Furthermore, EGCG dose-dependently
      inhibited lipid accumulation in maturing preadipocytes. DISCUSSION: These results
      demonstrate that EGCG can act directly to inhibit differentiation of
      preadipocytes and to induce apoptosis of mature adipocytes and, thus, could be an
      important adjunct in the treatment of obesity.

PMID- 15976141
TI  - High-fat diet-induced ultradian leptin and insulin hypersecretion are absent in
      obesity-resistant rats.
AB  - OBJECTIVE: Sprague-Dawley rats fed a high-fat diet (HFD) are either obesity prone
      (OP) or obesity resistant (OR). We tested the hypothesis that differences in the
      ultradian rhythmic patterns of insulin and ghrelin in OP vs. OR rats promote
      obesity in OP rats. RESEARCH METHODS AND PROCEDURES: Rats were fed regular chow
      or an HFD, and ultradian fluctuations in leptin, insulin, and ghrelin were
      analyzed in blood samples collected at 5-minute intervals from intrajugular
      cannulae of freely moving rats. RESULTS: Regular chow feeding resulted in a slow
      weight gain accompanied by small increases in insulin and leptin and a decrease
      in ghrelin discharge, with only the pulse amplitude significantly altered.
      Similar changes were observed in OR rats, despite HFD consumption. In contrast,
      OP rats exhibited a high rate of weight gain and marked hyperinsulinemia,
      hyperleptinemia, and hypoghrelinemia; amplitude was altered, but frequency was
      stable. In a short-term experiment, HFD elicited similar secretory patterns of
      smaller magnitude even in the absence of weight gain. DISCUSSION: We showed that
      three hormonal signals of disparate origin involved in energy homeostasis were
      secreted in discrete episodes, and only the pulse amplitude component was
      vulnerable to age and HFD consumption. Increases in insulin and leptin and
      decreases in ghrelin pulse amplitude caused by HFD were exaggerated in OP rats
      relative to OR rats and preceded the weight increase. These findings show that a
      distinct genetic predisposition in the endocrine organs of OR rats confers
      protection against high-fat intake-induced ultradian hypersecretion of obesity
      promoting hormonal signals.

PMID- 15976142
TI  - Oligofructose promotes satiety in rats fed a high-fat diet: involvement of
      glucagon-like Peptide-1.
AB  - OBJECTIVE: To analyze the putative interest of oligofructose (OFS) in the
      modulation of food intake after high-fat diet in rats and to question the
      relevance of the expression and secretion of intestinal peptides in that context.
      RESEARCH METHODS AND PROCEDURES: Male Wistar rats were pretreated with standard
      diet or OFS-enriched (10%) standard diet for 35 days followed by 15 days of high
      fat diet enriched or not with OFS (10%) treatment. Body weight, food intake,
      triglycerides, and plasma ghrelin levels were monitored during the treatment. On
      day 50, rats were food-deprived 8 hours and anesthetized for blood and intestinal
      tissue sampling for further proglucagon mRNA, glucagon-like peptide (GLP)-1, and
      GLP-2 quantification. RESULTS: The addition of OFS in the diet protects against
      the promotion of energy intake, body weight gain, fat mass development, and serum
      triglyceride accumulation induced by a high-fat diet. OFS fermentation leads to
      an increase in proglucagon mRNA in the cecum and the colon and in GLP-1 and GLP-2
      contents in the proximal colon, with consequences on the portal concentration of
      GLP-1 (increase). A lower ghrelin level is observed only when OFS is added to the
      standard diet of rats. DISCUSSION: In rats exposed to high-fat diet, OFS is,
      thus, able to modulate endogenous production of gut peptides involved in appetite
      and body weight regulation. Because several approaches are currently used to
      treat type 2 diabetes and obesity with limited effectiveness, dietary fibers such
      as OFS, which promote the endogenous production of gut peptides like GLP-1, could
      be proposed as interesting nutrients to consider in the management of fat intake
      and associated metabolic disorders.

PMID- 15976143
TI  - High-density lipoprotein apolipoprotein A-I kinetics in obesity.
AB  - OBJECTIVE: Low plasma concentrations of high-density lipoprotein (HDL)
      cholesterol and apolipoprotein A-I (apoA-I) are independent predictors of
      coronary artery disease and are often associated with obesity and the metabolic
      syndrome. However, the underlying kinetic determinants of HDL metabolism are not
      well understood. RESEARCH METHODS AND PROCEDURES: We pooled data from 13 stable
      isotope studies to investigate the kinetic determinants of apoA-I concentrations
      in lean and overweight-obese individuals. We also examined the associations of
      HDL kinetics with age, sex, BMI, fasting plasma glucose, fasting insulin,
      Homeostasis Model Assessment score, and concentrations of apoA-I, triglycerides,
      HDL-cholesterol and low-density lipoprotein-cholesterol. RESULTS: Compared with
      lean individuals, overweight-obese individuals had significantly higher HDL apoA
      I fractional catabolic rate (0.21+/-0.01 vs. 0.33+/-0.01 pools/d; p<0.001) and
      production rate (PR; 11.3+/-4.4 vs. 15.8+/-2.77 mg/kg per day; p=0.001). In the
      lean group, HDL apoA-I PR was significantly associated with apoA-I concentration
      (r=0.455, p=0.004), whereas in the overweight-obese group, both HDL apoA-I
      fractional catabolic rate (r=-0.396, p=0.050) and HDL apoA-I PR (r=0.399,
      p=0.048) were significantly associated with apoA-I concentration. After
      adjustment for fasting insulin or Homeostasis Model Assessment score, HDL apoA-I
      PR was an independent predictor of apoA-I concentration. DISCUSSION: In
      overweight-obese subjects, hypercatabolism of apoA-I is paralleled by an
      increased production of apoA-I, with HDL apoA-I PR being the stronger determinant
      of apoA-I concentration. This could have therapeutic implications for the
      management of dyslipidemia in individuals with low plasma HDL-cholesterol.

PMID- 15976144
TI  - Adiposity in middle-aged women is associated with genetic taste blindness to 6-n
      propylthiouracil.
AB  - OBJECTIVE: Taste blindness to the bitterness of 6-n-propylthiouracil (PROP) may
      be a genetic marker for food preferences and dietary choices that ultimately
      influence body weight. A previous study in middle-aged women showed that those
      who were taste blind to PROP (i.e., nontasters) had higher BMIs than those with
      the greatest sensitivity to PROP (i.e., supertasters). This study tested the
      hypothesis that the nontaster phenotype was associated with greater adiposity in
      middle-aged women. RESEARCH METHODS AND PROCEDURES: Forty women with a mean BMI
      of 26.6+/-1.3 kg/m2 and a mean age of 41.8+/-1.8 years were recruited from the
      local community. They were classified as nontasters (n=8), medium tasters (n=18),
      or supertasters (n=14) of PROP using a filter paper screening procedure.
      Anthropometric measures included height, weight, body fatness, triceps skinfold
      thickness, and waist circumference. Dietary restraint and disinhibition were also
      measured to assess cognitions associated with body weight. RESULTS: BMI was 6.2
      units higher in nontaster women compared with supertaster women (29.7+/-0.9 vs.
      23.5+/-0.9, respectively; p<0.05). Body fatness (p<0.01) and triceps skinfold
      thickness (p<0.05) were also higher in these women. Waist circumference showed a
      trend in the appropriate direction. Although disinhibition was associated with
      greater adiposity, the relation between PROP status and adiposity was not altered
      after controlling for disinhibition. DISCUSSION: The PROP nontaster phenotype was
      strongly associated with several measures of adiposity in middle-aged women.
      These data confirm our previous findings and suggest that the PROP polymorphism
      may be a reliable indicator of weight gain susceptibility.

PMID- 15976145
TI  - Regulation of global gene expression by ovariectomy and estrogen in female
      adipose tissue.
AB  - OBJECTIVE: To study the effects of ovariectomy (OVX) and estrogen replacement on
      global gene expression in white adipose tissue. RESEARCH METHODS AND PROCEDURES:
      Female mice were randomly divided into four groups: 1) intact, 2) OVX, 3) OVX
      plus estradiol (E2) injection 3 hours before death (E(2)-3 hours), and 4) E(2)-24
      hours. The serial analysis of gene expression was performed to detect the
      transcriptomic changes. RESULTS: A total of 15 transcripts, including several
      novel transcripts, were found to be modulated by OVX or E2 (p<0.05). Secreted
      acidic cysteine-rich glycoprotein, which regulates the extracellular matrix (ECM)
      components, was increased after OVX. Moreover, OVX up-regulated several
      transcripts involved in ECM, such as procollagen types Ialpha1 and 2. In cell
      defense, glutathione peroxidase 3 was lower in OVX than in intact mice.
      Cytochrome c oxidase I and three novel transcripts were up-regulated by estrogen
      treatment. DISCUSSION: This study underlines the importance of cell shape and ECM
      regulation by OVX on adiposity. Moreover, some novel transcripts may also play a
      relevant role in OVX-induced obesity and estrogen therapy.

PMID- 15976147
TI  - Cluster analysis methods help to clarify the activity-BMI relationship of Chinese
      youth.
AB  - OBJECTIVE: To use cluster analysis to create patterns of overall activity and
      inactivity in a diverse sample of Chinese youth and to evaluate their use in
      predicting overweight status. RESEARCH METHODS AND PROCEDURES: The study
      populations were drawn from the 1997 and 2000 years of the longitudinal China
      Health and Nutrition Survey, comprised of 2702 and 2641 schoolchildren in the
      1997 and 2000 cross-sectional samples, respectively, and 1175 children in the
      longitudinal cohort. Cluster analysis was used to group children into
      nonoverlapping activity/inactivity "clusters" that were subsequently used in
      models of prevalent and incident overweight. Results were compared with
      traditional models, with activity and inactivity coded separately, to assess
      whether further insight was gained with the cluster analysis methodology.
      RESULTS: Moderately and highly active youth were shown to have significantly
      decreased odds of overweight in both cross-sectional and longitudinal analyses
      using cluster analysis. In incident longitudinal models, youth in the high
      activity/high inactivity cluster had the lowest odds of overweight [odds
      ratio=0.12 (0.03, 0.44)]; in contrast, results from traditional models failed to
      show any significant relationship between overweight and activity or inactivity.
      DISCUSSION: Cluster analysis methods allow researchers to simultaneously capture
      activity and inactivity in new ways. In this comparative study, only with the
      clustering methodology did we find a significant effect of activity on incident
      overweight, furthering our ability to examine this complex relationship.
      Interestingly, no effect of increasing levels of inactivity was observed using
      either method, indicating that activity seems to be the more important
      determinant of overweight in this population.

PMID- 15976148
TI  - Provision of foods differing in energy density affects long-term weight loss.
AB  - OBJECTIVE: The energy density (kilocalories per gram) of foods influences short
      term energy intake. This 1-year clinical trial tested the effect on weight loss
      of a diet incorporating one or two servings per day of foods equal in energy but
      differing in energy density. RESEARCH METHODS AND PROCEDURES: Dietitians
      instructed 200 overweight and obese women and men to follow an exchange-based
      energy-restricted diet. Additionally, subjects were randomized to consume daily
      either one or two servings of low energy-dense soup, two servings of high energy
      dense snack foods, or no special food (comparison group). RESULTS: All four
      groups showed significant weight loss at 6 months that was well maintained at 12
      months. The magnitude of weight loss, however, differed by group (p=0.006). At 1
      year, weight loss in the comparison (8.1+/-1.1 kg) and two-soup (7.2+/-0.9 kg)
      groups was significantly greater than that in the two-snack group (4.8+/-0.7 kg);
      weight loss in the one-soup group (6.1+/-1.1 kg) did not differ significantly
      from other groups. Weight loss was significantly correlated with the decrease in
      dietary energy density from baseline at 1 and 2 months (p=0.0001) but not at 6
      and 12 months. DISCUSSION: On an energy-restricted diet, consuming two servings
      of low energy-dense soup daily led to 50% greater weight loss than consuming the
      same amount of energy as high energy-dense snack food. Regularly consuming foods
      that are low in energy density can be an effective strategy for weight
      management.

PMID- 15976146
TI  - Adipose gene expression patterns of weight gain suggest counteracting steroid
      hormone synthesis.
AB  - OBJECTIVE: To identify early molecular changes in weight gain, using analysis of
      gene expression changes in adipose tissue of mice fed well-defined humanized
      (Western) high-fat and low-fat (control) diets during a short (3- to 5-week) time
      interval. RESEARCH METHODS AND PROCEDURES: An adipose-enriched cDNA microarray
      was constructed and used for the expression analyses of visceral adipose tissues
      of wildtype young adult C57BL/6J male mice on different diets. RESULTS: Mice on a
      high-fat diet had significantly higher body weight (at most, 9.6% greater) and
      adipose tissue weights compared with mice on a control diet. Gene expression
      analyses revealed 31 transcripts significantly differentially expressed in
      visceral adipose tissue between the diet groups. Most of these genes were
      expressed more on the high-fat diet. They mainly encode proteins involved in
      cellular structure (e.g., myosin, procollagen, vimentin) and lipid metabolism
      (e.g., leptin, lipoprotein lipase, carbonic anhydrase 3). This increase in gene
      expression was accompanied by a decrease in oxidative phosphorylation and
      carbohydrate metabolism (ATP citrate lyase). Importantly, genes belonging to
      steroid hormone biosynthesis (3beta-hydroxysteroid dehydrogenase-1, cholesterol
      side-chain cleavage cytochrome P450, and steroid-11beta-hydroxylase) were all
      expressed less in mice on a high-fat diet. DISCUSSION: A short time period of 3
      to 5 weeks of high-fat feeding altered gene expression patterns in visceral
      adipose tissue in male mice. Gene expression changes indicate initiation of
      adipose tissue enlargement and the down-regulation of adipose steroid hormone
      biosynthesis. The latter suggests a mechanism by which initial progression toward
      weight gain is counteracted.

PMID- 15976149
TI  - Factors that influence food amount ratings by white, Hispanic, and Asian samples.
AB  - OBJECTIVE: Two studies explored in nonclinical samples variables that may
      influence meal size assessments. RESEARCH METHODS AND PROCEDURES: In Study 1, the
      contribution of dietary restraint, weight, depressive symptoms, and gender to
      ratings on the Food Amount Rating Scale was examined in 153 white women and 121
      white men; in Study 2, the contribution of dietary restraint, weight, ethnicity,
      and ethnic group identification to Food Amount Rating Scale ratings was examined
      in 67 Asian, 81 Hispanic, and 107 white women. RESULTS: Study 1 indicated that
      food amounts were rated as larger when rated by male rather than female raters
      (male rater, mean=62.37, SD=1.14; female rater, mean=59.28, SD=0.89), for female
      rather than male targets (male target, mean=56.16, SD=0.97; female target,
      mean=64.87, SD=1.02), and by restrained rather than unrestrained eaters
      (restrained, mean=63.14, SD=1.11; unrestrained, mean=58.69, SD=0.91). Study 2
      indicated that food amounts were rated as larger when rated by restrained eaters
      (restrained, mean=67.53, SD=1.21; unrestrained, mean=64.99, SD=1.09), Hispanic
      women (Asian, mean=64.59, SD=1.61; Hispanic, mean=68.71, SD=1.30; white,
      mean=65.41, SD=1.34), and underweight women (underweight, mean=70.38, SD=1.68;
      normal weight, mean=64.52, SD=0.93; overweight: mean=64.23, SD=1.64). DISCUSSION:
      Food amount judgments may be influenced by personal characteristics. Future
      research should examine whether variation in food amount judgments is related to
      dieting behavior, disordered eating, or obesity.

PMID- 15976150
TI  - Gender differences in associations of eating pathology between mothers and their
      adolescent offspring.
AB  - OBJECTIVE: To study the association of eating pathology between mothers and their
      adolescent offspring in a population sample. RESEARCH METHODS AND PROCEDURES: The
      participants were 481 women (mean age, 47+/-SD 5 years; BMI, 25+/-4 kg/m2) and
      their 481 adolescent children 16 to 17 years old (BMI, 21+/-3 kg/m2) of the
      Stockholm Weight Development Study. Assessment methods were the Three-Factor
      Eating Questionnaire Revised 18 and the Eating Disorder Inventory 2. RESULTS: A
      higher body weight was most related to cognitive restraint for adolescents and to
      emotional eating for adult women. A mother-daughter link could be identified for
      eating pathology, with the strongest link found for emotional eating. No mother
      son link could be identified. Age subgroup analyses revealed a stronger mother
      daughter link for body attitudes in younger mothers and for cognitive restraint
      in older mothers. DISCUSSION: Gender differences revealed that eating pathology
      was shared by mothers and daughters but not by mothers and sons. A psychological
      strategy such as eating as a response to negative emotions was most interrelated
      between mothers and daughters. Younger mothers shared more attitudes toward the
      body with their daughters, whereas older mothers shared more restrictive eating
      behaviors with their daughters. The mother-daughter links found may be due to
      gender-specific genetic and psychological family transmission and gender-specific
      environmental influences. The sons' eating behaviors seem to be more independent
      and would be formed by other factors than for the girls.

PMID- 15976151
TI  - Cognitive behavioral therapy and fluoxetine as adjuncts to group behavioral
      therapy for binge eating disorder.
AB  - OBJECTIVE: Although binge eating disorder is a common and distressing concomitant
      of obesity, it has not yet been established whether affected individuals
      presenting to behavioral weight control programs should receive specialized
      treatments to supplement standard treatment. This study was designed to examine
      the added benefit of two adjunctive interventions, individual cognitive
      behavioral therapy (CBT) and fluoxetine, offered in the context of group
      behavioral weight control treatment. RESEARCH METHODS AND PROCEDURES: One hundred
      sixteen overweight/obese women and men with binge eating disorder were all
      assigned to receive a 16-session group behavioral weight control treatment over
      20 weeks. Simultaneously, subjects were randomly assigned to receive
      CBT+fluoxetine, CBT+placebo, fluoxetine, or placebo in a two-by-two factorial
      design. Outcome measures, assessed at the end of the 16-session acute treatment
      phase, included binge frequency, weight, and measures of eating-related and
      general psychopathology. RESULTS: Overall, subjects showed substantial
      improvement in binge eating and both general and eating-related psychopathology,
      but little weight loss. Subjects who received individual CBT improved more in
      binge frequency than did those not receiving CBT (p<0.001), and binge abstinence
      was significantly more common in subjects receiving CBT vs. those who did not
      (62% vs. 33%, p<0.001). Fluoxetine treatment was associated with greater
      reduction in depressive symptoms (p<0.05). The 54 subjects who achieved binge
      abstinence improved more on all measures than the 62 subjects who did not. In
      particular, these subjects lost, on average, 6.2 kg compared with a gain of 0.7
      kg among non-abstainers. DISCUSSION: Adjunctive individual CBT results in
      significant additional binge reduction in obese binge eaters receiving standard
      behavioral weight control treatment.

PMID- 15976152
TI  - The relationship between parent and child self-reported adherence and weight
      loss.
AB  - OBJECTIVE: Better adherence to treatment strategies in family-based behavioral
      weight control programs may lead to greater weight reduction and improved weight
      maintenance in youth. This study assessed the influence of child and parent self
      reported adherence to behavioral strategies on changes in 2-year child and parent
      percentage overweight. RESEARCH METHODS AND PROCEDURES: Participants included 8-
      to 12-year-old children in >or= 85th BMI percentile and their parents from 110
      families taking part in two family-based randomized controlled weight control
      studies. This study examined whether self-reported adherence to behavioral
      strategies measured at 24 months increased prediction of child and parent
      percentage overweight change through 24-month follow-up after accounting for
      other factors that may influence weight change. RESULTS: Child adherence to
      weighing and to preplanning for celebrations where high-fat foods are served and
      parent adherence to praising the child and modeling healthy eating habits
      predicted 24-month child percentage overweight change (p<0.001). Child adherence
      to recording food and calories and parent adherence to modeling healthy eating
      habits predicted 24-month parent percentage overweight change (p<0.001). In
      hierarchical regression models, child weighing and preplanning and parent
      modeling were significant (p<0.01) incremental predictors (r2 of 24.8%) of 24
      month child percentage overweight. Child recording and parent modeling were
      significant (p<0.01) incremental predictors (r2 of 14%) of parent 24-month
      percentage overweight change. DISCUSSION: Child and parent adherence to specific
      components of family-based behavioral weight control treatment are independent
      predictors of long-term child and parent percentage overweight change.

PMID- 15976153
TI  - Physical activity and psychosocial correlates in normal weight and overweight 11
      to 19 year olds.
AB  - OBJECTIVE: This study examined differences in (1) psychosocial correlates of
      physical activity and in (2) physical activity within different contexts and
      sedentary behaviors between normal weight and overweight adolescents. It further
      explored whether the prediction of physical activity by the psychosocial
      correlates is different in normal weight and overweight adolescents. RESEARCH
      METHODS AND PROCEDURE: A community sample of 6078 11 to 19 year olds from 38
      secondary schools, which were randomly selected throughout the country, completed
      a validated computerized questionnaire about physical activity, sedentary
      behaviors, and psychosocial correlates. Differences in mean scores on the
      psychosocial correlates and on the self-rated physical activity were analyzed
      between the normal weight (n=5563) and the overweight (n=515, 8.5%) group.
      RESULTS: This study showed that overweight adolescents do less intense physical
      activities (p<0.001) and have less favorable psychosocial correlates related to
      physical activity (p<0.001) than their normal weight counterparts. However, the
      strength of the associations between psychosocial variables and total physical
      activity were comparable in overweight and normal weight adolescents. More
      support from family and friends, more fun in physical activity, higher self
      efficacy, the perception of more competition benefits, and the perception of less
      lack of interest were all associated with higher total levels of physical
      activity. The results suggest that no specific tailoring on psychosocial
      correlates of physical activity is necessary for overweight adolescents compared
      with normal weight ones. DISCUSSION: Both overweight and normal weight
      adolescents can be approached by interventions focusing on the same psychosocial
      variables to increase physical activity.

PMID- 15976154
TI  - Utility of childhood BMI in the prediction of adulthood disease: comparison of
      national and international references.
AB  - OBJECTIVE: To determine whether the U.S. Centers for Disease Control and
      Prevention (CDC; CDC Reference) or International Obesity Task Force (IOTF; IOTF
      Reference) BMI cut-off points for classifying adiposity status in children are
      more effective at predicting future health risk. RESEARCH METHODS AND PROCEDURES:
      The sample (N=1709) included 4- to 15-year-old (at baseline) boys and girls from
      the Bogalusa Heart Study. Overweight and obesity status were determined using
      both the CDC Reference and IOTF Reference BMI cut-off points at baseline. The
      ability of childhood overweight and obesity, determined from the two BMI
      classification systems, to predict obesity and metabolic disorders in young
      adulthood (after a 13- to 24-year follow-up) was then compared. RESULTS:
      Independently of the classification system employed to determine adiposity based
      on childhood BMI, the odds of being obese and having all of the metabolic
      disorders in young adulthood were significantly (p<0.05) higher in the overweight
      and obese groups by comparison with the nonoverweight groups. Childhood
      overweight and obesity, determined by both the CDC Reference and IOTF Reference,
      had a low sensitivity and a high specificity for predicting obesity and metabolic
      disorders in young adulthood. Overweight and obesity as determined by the CDC
      Reference were slightly more sensitive and slightly less specific than the
      corresponding values based on the IOTF Reference. DISCUSSION: Overweight and
      obesity during childhood, as determined by both the CDC and IOTF BMI cut-off
      points, are strong predictors of obesity and coronary heart disease risk factors
      in young adulthood. The differences in the predictive capacity of the CDC
      Reference and IOTF Reference are, however, minimal.

PMID- 15976155
TI  - Prevalence of uncomplicated obesity in an Italian obese population.
AB  - OBJECTIVE: The existence of healthy obese subjects has been suggested but not
      clearly reported. We sought to address the prevalence of uncomplicated obesity
      and adverse risk factors in a large Italian obese population. RESEARCH METHODS
      AND PROCEDURES: This was a cross-sectional study of a population of consecutive
      Italian obese subjects. We studied 681 obese subjects (514 women and 167 men),
      with a mean age of 41.1+/-13.9 years (range, 16 to 77 years), mean BMI of 40.2+/
      7.6 kg/m2 (range, 30 to 89.8 kg/m2), and a history of obesity for 20.5+/-7 years
      (range, 10.5 to 30 years). Anthropometric, metabolic, cardiac, and obesity
      related risk factors were evaluated. RESULTS: The prevalence of uncomplicated
      subjects was 27.5%, independent of BMI and duration of obesity. The youngest
      group of obese subjects showed a higher, but not statistically significantly
      higher, prevalence of uncomplicated obesity. No statistical difference for the
      prevalence of impaired fasting glucose, glucose intolerance, high triglycerides,
      high total cholesterol, low-density lipoprotein cholesterol, and high-density
      lipoprotein cholesterol among BMI categories (from mild to extremely severe
      obesity degree) was found. Obese subjects with BMI>50 kg/m2 showed a higher
      prevalence of high blood pressure only when they were compared with the group
      with a BMI of 30 to 35 kg/m2 (p<0.01). Obese subjects with BMI>40 kg/m2 showed a
      higher prevalence of hyperinsulinemia than subjects with BMI 30 to 35 kg/m2
      (p<0.01). DISCUSSION: This study shows that a substantial part of an Italian
      obese population has uncomplicated obesity, and the prevalence of adverse risk
      factors in this sample is unexpectedly low and partially independent of obesity
      degree. Uncomplicated obesity could represent a well-defined clinical entity.

PMID- 15976156
TI  - Weight and height growth rate and the timing of adiposity rebound.
AB  - OBJECTIVE: Adiposity rebound occurs when the ratio of the velocities of
      log(weight) to log(height) changes from <2 to >2. This study examined the timing
      of adiposity rebound in the context of the velocities of weight and height in
      early childhood because it is not known whether faster weight gain or slower gain
      in stature is the more important determinant. RESEARCH METHODS AND PROCEDURES:
      This was a longitudinal study of 406 boys and 397 girls born in Dunedin, New
      Zealand, in 1972 and 1973. Each child's height and weight were measured at 3
      years of age and at least twice more as part of their two yearly assessments
      until 11 years of age. RESULTS: The mean age of adiposity rebound was 6.6+/-1.10
      years (SD) for boys and 6.0+/-1.21 years for girls. After adjusting for sex, the
      correlations between the timing of rebound and z-scores for BMI, weight, and
      height at rebound were -0.35, -0.30, and -0.14, respectively. Correlations
      between the timing of rebound and estimated values of weight and height
      velocities at 3 years were -0.48 and -0.00. The correlations with BMI and waist
      girth at 26 years were -0.39 and -0.35. DISCUSSION: Children with an earlier
      adiposity rebound were heavier and had above average BMIs. Early rebound is the
      result of higher rates of weight gain, measured in percentage terms, rather than
      slower than average accrual of stature. This suggests that restraining weight
      gain could delay adiposity rebound and prevent obesity in early adulthood.

PMID- 15976157
TI  - Sequential avulsion of the anterior inferior iliac spine in an adolescent long
      jumper.
AB  - We present here an unusual case of a sequential avulsion fracture of the anterior
      inferior iliac spine (AIIS), occurring first in the right and then the left AIIS,
      during long jump attempts. The case of a 17 year old boy with pain around his
      right groin, which first occurred during a long jump attempt, is presented.
      Radiographic examination revealed an avulsion fracture of the right AIIS. After
      conservative treatment, full athletic activity was allowed 2 months after the
      injury. However, 4 months later the patient returned with a similar pain in the
      opposite side of his groin. Radiographs revealed another fracture of the left
      AIIS. The boy underwent the same treatment protocol; he was examined with
      isokinetic dynamometry. No complication or re-injury occurred during the 2 year
      follow up period. In the present study, we introduce the first case of a
      sequential bilateral AIIS avulsion fracture caused by a long jump.

PMID- 15976159
TI  - To every thing there is a season.

PMID- 15976158
TI  - Ventricular septal defect in a world class runner.
AB  - We report the case of an elite male, East African endurance runner (18 years old)
      who ranked in the top 15 in the World Cross Country Championships (sub 21 year
      old category) despite having a ventricular septal defect (VSD; width: 0.22 cm)
      that was diagnosed 2 weeks after this event with echocardiographic evaluation.
      This athlete was a moderate altitude native ( approximately 3000 m). Cardiac
      dimensions were within normal limits and no significant pathological signs were
      observed. His Vo(2max) was relatively low given his performance level (67.9 ml
      kg(-1) min(-1)). Despite his limited training background (only 1 year), his
      running economy was, however, better than the values reported in our laboratory
      for Caucasian runners of the same age. Further cardiological follow up might
      confirm that the VSD causes no pathological effects or any performance detriment
      in future years.

PMID- 15976160
TI  - Women will do it in the long run.

PMID- 15976161
TI  - A systematic review and meta-analysis of clinical trials on physical
      interventions for lateral epicondylalgia.
AB  - A systematic review of the literature on the effectiveness of physical
      interventions for lateral epicondylalgia (tennis elbow) was carried out. Seventy
      six randomised controlled trials were identified, 28 of which satisfied the
      minimum criteria for meta-analysis. The evidence suggests that extracorporeal
      shock wave therapy is not beneficial in the treatment of tennis elbow. There is a
      lack of evidence for the long term benefit of physical interventions in general.
      However, further research with long term follow up into manipulation and exercise
      as treatments is indicated.

PMID- 15976162
TI  - Neovascularisation and pain in jumper's knee: a prospective clinical and
      sonographic study in elite junior volleyball players.
AB  - BACKGROUND: The nature of tendon neovascularisation associated with pain over
      time has not been studied. OBJECTIVE: To prospectively study the patellar tendons
      in elite junior volleyball players. METHODS: The patellar tendons in all students
      at the Swedish National Centre for high school volleyball were evaluated
      clinically and by ultrasonography (US) and Power Doppler (PD) sonography.
      RESULTS: Altogether 120 patellar tendons were followed for 7 months. At
      inclusion, jumper's knee was diagnosed clinically in 17 patellar tendons. There
      were structural changes on US in 14 tendons, in 13 of which PD sonography showed
      neovascularisation. There were 70 clinically normal tendons with normal US and PD
      sonography, 24 clinically normal tendons with abnormal US but normal PD
      sonography, and nine clinically normal tendons with abnormal US and
      neovascularisation on PD sonography. At 7 month follow up, jumper's knee was
      diagnosed clinically and by US in 19 patellar tendons, in 17 of which there was
      neovascularisation. Three of nine clinically normal tendons with structural
      changes and neovascularisation at inclusion developed jumper's knee. Two of 24
      tendons clinically normal at inclusion, with abnormal US but normal PD
      sonography, developed jumper's knee with abnormal US and neovascularisation on PD
      sonography. A total of 20 clinically normal tendons with normal US and PD
      sonography at inclusion developed structural tendon changes and 12 of these also
      developed neovascularisation. CONCLUSIONS: The clinical diagnosis of jumper's
      knee is most often associated with neovascularisation in the area with structural
      tendon changes. The finding of neovessels might indicate a deterioration of the
      condition.

PMID- 15976164
TI  - Functional ankle control of rock climbers.
AB  - OBJECTIVE: To evaluate whether rock climbing type exercise would be of value in
      rehabilitating ankle injuries to improve ankle stability and coordination.
      [figure: see text] METHODS: A group of 25 rock climbers was compared with a group
      of 26 soccer players. All were male, uninjured, and exercised three to four times
      a week. Active ankle stability was evaluated by one leg stand stabilometry
      (measurement of migration of the centre of gravity) and measurements of maximum
      strength of ankle isokinetic concentric flexion and extension (Cybex). RESULTS:
      The rock climbers showed significantly better results in the stabilometry and
      greater absolute and relative maximum strength of flexion in the ankle. The
      soccer players showed greater absolute but not relative strength in extension.
      CONCLUSION: Rock climbing, because of its slow and controlled near static
      movements, may be of value in the treatment of functional ankle instability.
      However, it has still to be confirmed whether it is superior to the usual
      rehabilitation exercises such as use of the wobble board.

PMID- 15976165
TI  - Lactate threshold responses to a season of professional British youth soccer.
AB  - OBJECTIVE: To examine the changes in aerobic endurance performance of
      professional youth soccer players throughout the soccer season. METHODS: Nine
      youth soccer players were tested at six different time points throughout the
      soccer season by sub-maximal blood lactate assessment, using an incremental
      treadmill protocol. Whole blood lactate concentration and heart frequency (Hf)
      were determined at each exercise stage. Running velocities at the first lactate
      inflection point (v-T(lac)) and at a blood lactate concentration of 4 mmol l(-1)
      (v-4mM) were determined. RESULTS: Running velocity at the two lactate thresholds
      increased from the start of pre-season training to the early weeks of the
      competitive season, from 11.67 (0.29) to 12.96 (0.28) km h(-1) for v-T(lac), and
      from 13.62 (0.25) to 14.67 (0.24) km h(-1) for v-4mM (p<0.001). However, v-T(lac
      )and v-4mM when expressed relative to maximum heart frequency (Hf(max)) remained
      unchanged. The Hf to blood lactate concentration relationship was unchanged after
      the pre-season training period. The two expressions of lactate threshold did not
      reveal differences between each other. CONCLUSION: Running velocity at v-T(lac
      )and v-4mM increased significantly over the pre-season period, but v-T(lac )and v
      4mM were unchanged when expressed relative to Hf(max). This finding may indicate
      that increased endurance performance may be mainly attributable to alterations in
      Vo(2max). Although lactate assessment of soccer players is useful for determining
      endurance training adaptations in soccer players, additional assessment of the
      other two determinants of endurance performance (Vo(2max) and running economy)
      may provide more useful information for determining physiological adaptations
      resulting from soccer training and training interventions.

PMID- 15976166
TI  - A comparison of the physiological profiles of elite Gaelic footballers, hurlers,
      and soccer players.
AB  - BACKGROUND: Gaelic football, soccer, and hurling are prominent field games in
      Ireland and involve participants undertaking a variety of playing tasks and
      skills which place various physiological demands on the participants. The aim of
      this study was to evaluate and compare the mid-season physiological profiles of
      elite players. METHODS: Physiological assessment was carried out on 29 inter
      county Gaelic footballers, 30 inter-county hurlers, and 21 League of Ireland
      soccer players. RESULTS: Significant differences were reported for % body fat
      (p<0.05), aerobic capacity (p<0.05), flexibility (p<0.05), upper body strength
      (p<0.05), upper body strength endurance (p<0.05), abdominal endurance (p<0.05),
      and speed endurance (p<0.05), while there were no differences recorded for
      height, weight, or speed levels. A relatively heterogeneous body size is evident
      for all three sports. Soccer players had lower body fat levels, greater aerobic
      capacity, greater strength endurance, and greater flexibility compared to both
      Gaelic footballers and hurlers, possibly due to specific training and
      conditioning programmes or physical adaptation to match play The greater strength
      of both Gaelic footballers and hurlers and the superior speed endurance levels of
      Gaelic footballers also reflect the physical nature of the sports. Similar speed
      levels amongst all three sports reflect the importance of speed for performance.
      CONCLUSIONS: The various physiological attributes for Gaelic football, soccer,
      and hurling reflect the physical requirements for success and participation in
      each of these field games.

PMID- 15976167
TI  - Cervical muscle strength measurement in two groups of elite Greco-Roman and free
      style wrestlers and a group of non-athletic subjects.
AB  - BACKGROUND: Free style and Greco-Roman are two types of wrestling. [figure: see
      text] OBJECTIVES: The aim of this study was to examine the maximal isometric
      strength of cervical extension (ISCE) and the maximal isometric strength of
      cervical flexion (ISCF) in two groups of elite wrestlers and a group of non
      athletic subjects. METHODS: Fourteen elite Greco-Roman wrestlers (aged 19-25
      years), 16 elite free style wrestlers (aged 18-25 years), and 16 non-athletic
      subjects (aged 18-25 years) participated in this study. All wrestlers competed at
      international level with the Iranian national team. Maximum voluntary
      contractions (MVC) of cervical extensor and flexor muscles were measured using a
      custom made device. The ratios of ISCE to weight (ISCE/weight), ISCF to weight
      (ISCF/weight), and ISCF to ISCE (ISCF/ISCE) were calculated for group
      comparisons. Pearson product moment test was used to estimate correlation between
      maximal isometric strength measurements and anthropometric variables. A one way
      analysis of variance was computed to compare ISCE/weight, ISCF/weight, and
      ISCF/ISCE among groups. RESULTS: There was significant correlation between
      maximum cervical extension and flexion strengths and weight in all groups
      (p<0.05, n = 46). The ratios of cervical muscle strengths to weight were
      significantly higher in wrestlers than in non-athletic subjects (p<0.00). Greco
      Roman wrestlers appeared to be stronger than free style wrestlers following
      comparison of all ratios. CONCLUSIONS: Neck muscle force measurements may be a
      useful test for athletes in combat sports like wrestling. They can be applied to
      identify the weakness of a group of muscles in the neck area and to devise a
      proper training program.

PMID- 15976168
TI  - Risk of cervical injuries in mixed martial arts.
AB  - BACKGROUND: Mixed martial arts have rapidly succeeded boxing as the world's most
      popular full contact sport, and the incidence of injury is recognised to be high.
      OBJECTIVE: To assess qualitatively and quantitatively the potential risk for
      participants to sustain cervical spine and associated soft tissue injuries.
      METHODS: Four commonly performed manoeuvres with possible risks to the cervical
      spine were analysed with respect to their kinematics, and biomechanical models
      were constructed. RESULTS: Motion analysis of two manoeuvres revealed strong
      correlations with rear end motor vehicle impact injuries, and kinematics of the
      remaining two suggested a strong risk of injury. Mathematical models of the
      biomechanics showed that the forces involved are of the same order as those
      involved in whiplash injuries and of the same magnitude as compression injuries
      of the cervical spine. CONCLUSIONS: This study shows that there is a significant
      risk of whiplash injuries in this sport, and there are no safety regulations to
      address these concerns.

PMID- 15976169
TI  - Assessment of ventilatory thresholds during graded and maximal exercise test
      using time varying analysis of respiratory sinus arrhythmia.
AB  - OBJECTIVE: To test whether ventilatory thresholds, measured during an exercise
      test, could be assessed using time varying analysis of respiratory sinus
      arrhythmia frequency (f(RSA)). METHODS: Fourteen sedentary subjects and 12
      endurance athletes performed a graded and maximal exercise test on a cycle
      ergometer: initial load 75 W (sedentary subjects) and 150 W (athletes),
      increments 37.5 W/2 min. f(RSA) was extracted from heart period series using an
      evolutive model. First (T(V1)) and second (T(V2)) ventilatory thresholds were
      determined from the time course curves of ventilation and ventilatory equivalents
      for O(2) and CO(2). RESULTS: f(RSA) was accurately extracted from all recordings
      and positively correlated to respiratory frequency (r = 0.96 (0.03), p<0.01). In
      21 of the 26 subjects, two successive non-linear increases were determined in
      f(RSA), defining the first (T(RSA1)) and second (T(RSA2)) f(RSA) thresholds. When
      expressed as a function of power, T(RSA1) and T(RSA2) were not significantly
      different from and closely linked to T(V1) (r = 0.99, p<0.001) and T(V2) (r =
      0.99, p<0.001), respectively. In the five remaining subjects, only one non-linear
      increase was observed close to T(V2). Significant differences (p<0.04) were found
      between athlete and sedentary groups when T(RSA1) and T(RSA2) were expressed in
      terms of absolute and relative power and percentage of maximal aerobic power. In
      the sedentary group, T(RSA1) and T(RSA2) were 150.3 (18.7) W and 198.3 (28.8) W,
      respectively, whereas in the athlete group T(RSA1) and T(RSA2) were 247.3 (32.8)
      W and 316.0 (28.8) W, respectively. CONCLUSIONS: Dynamic analysis of f(RSA)
      provides a useful tool for identifying ventilatory thresholds during graded and
      maximal exercise test in sedentary subjects and athletes.

PMID- 15976170
TI  - Impact of social standing on sports injury prevention in a WHO safe community:
      intervention outcome by household employment contract and type of sport.
AB  - OBJECTIVES: As physical activity is promoted as part of a healthy lifestyle,
      sports injuries are becoming an important public health concern in many
      countries. The objective of this study is to investigate rates of sports injuries
      before and after implementation of a WHO Safe Community program. METHODS: Sports
      injury data were collected pre- and post-implementation from all individuals
      below 65 years of age during 1 year in the targeted municipality (population
      41,000) and in a control municipality (population 26,000). A quasi-experimental
      design was used and individuals were divided into three categories based on
      household relationship to the labour market. RESULTS: There were no differences
      between socio-economic categories regarding pre-intervention injury rates. No
      statistically significant post-intervention changes in injury rate were observed
      in the control area or among any females in either area. In the intervention
      area, a statistically significant (p = 0.011) decrease in injury rate was
      observed among male members of households in which the vocationally important
      member was employed. A statistically significant decrease was observed in
      injuries sustained in team sports among male members of households in which the
      vocationally important member was employed (p = 0.001) and among members of
      households in which the vocationally important member was self employed (p<0.05).
      CONCLUSIONS: The study indicates areas for improvement in the civic network based
      WHO Safe Community model. The results show that females, participants in
      individual sports, and members of non-vocationally active households were less
      affected by the interventions. These facts have to be addressed in planning
      future community based sports injury prevention programmes and their evaluations.

PMID- 15976171
TI  - Vascularity and pain in the patellar tendon of adult jumping athletes: a 5 month
      longitudinal study.
AB  - BACKGROUND: This study investigated changes in tendon vascularity in 102 (67 men
      and 35 women) volleyball players over a 6 month competitive season. METHODS:
      Athletes were examined with both grey scale ultrasound and standardised colour
      Doppler settings. Vessel length and pain were measured each month on five
      separate occasions. Vascular tendons were divided into (i) those that were
      vascular on all occasions (persistent vascularity) and (ii) those that were
      vascular on more than two but less than five occasions (intermittent
      vascularity). RESULTS: A total of 41 of the 133 abnormal tendons were vascular on
      two or more occasions. Of these, 16 had persistent vascularity and 25 had
      intermittent vascularity. There was no significant difference in the prevalence
      of vascularity between men and women. None of the tendons had a pattern of
      vascularity over the season that could be clearly interpreted as the onset or
      resolution of vascularity. Subjects with changes in both tendons were more likely
      to have persistent vascularity (p = 0.045). Vessels were longer in tendons with
      persistent vascularity (p<0.000) and pain was significantly greater (p = 0.043)
      than in tendons with intermittent vascularity. Tendons with intermittent
      vascularity had similar pain scores on all days, whether or not they had
      detectable blood flow. CONCLUSIONS: These data suggest that the presence of blood
      vessels is more likely to be the source of pain than the blood flow in them.

PMID- 15976172
TI  - Injury history as a risk factor for incident injury in youth soccer.
AB  - OBJECTIVES: To determine if athletes with a self reported history of previous
      injury have a higher incident injury rate than athletes without a self reported
      injury history. METHODS: A prospective cohort study of Classic League soccer
      players playing at the level under 12 through under 18. Injury history forms were
      mailed to all registering Classic League soccer players in the North Carolina
      Youth Soccer Association during 1997-2000 (n = 7000); 1483 (19%) returned the
      baseline questionnaire and were followed up for injuries. RESULTS: There were
      5139 player-seasons of follow up and an estimated 171 957 athlete-exposures. More
      than half self reported an injury history (59.7%). Overall, the unadjusted
      incidence rate was 4.6 (95% confidence interval (CI) 4.3 to 4.9) incident
      injuries per 1000 athlete-exposures. Multivariate generalised Poisson regression
      modelling indicated that players with one previous injury had a twofold greater
      risk of incident injury (IRR = 2.6; 95% CI 2.0 to 3.3), and those with two or
      more previous injuries had a threefold greater risk of incident injury (IRR =
      3.0; 95% CI 2.3 to 3.8) compared with athletes with no previous injuries.
      CONCLUSIONS: Injury history was associated with an increased injury rate. This
      suggests that, even in these youth soccer players, those with an injury history
      may be at higher risk.

PMID- 15976173
TI  - Anatomical location of athletic injuries during training: a prospective two year
      study in 2701 athletes.

PMID- 15976175
TI  - Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in
      myeloma patients treated with high-dose therapy.
AB  - Fluorescence in situ hybridization (FISH) is more sensitive than conventional
      cytogenetics for recognizing chromosomal changes. Several FISH-detected
      abnormalities have been associated with inferior prognosis, including deletion of
      chromosomes 17 and 13 (Delta13) and t(4;14)(p16.3;q32). We analyzed the
      prognostic value of FISH testing in 238 patients who received high-dose therapy
      between January 1990 and September 2001. All patients had pretransplantation
      cytoplasmic immunoglobulin FISH done on cytospin slides from bone marrow
      aspirates for t(11;14), t(4;14), and -17(p13.1) (TP53). Time to progression and
      overall survival were significantly shorter for patients with t(4;14) and those
      with -17(p13.1) but were not affected by t(11;14). Overall survival was
      significantly shorter for patients with both t(4;14) and Delta13 abnormalities
      than for those with Delta13 alone (26.8 vs 18.8 months). In a multivariable
      analysis of the effect of Delta13 and t(4;14), the risk ratio for t(4;14) was
      greater than for Delta13 (2.6 vs 1.5). For high-dose therapy patients, -17(p13)
      and t(4;14) have clinical importance for estimating time to progression and
      overall survival. The presence of t(4;14) identifies a subset of patients whose
      time to progression is only 8.2 months. These patients receive minimal benefit
      from autologous stem cell transplantation and are candidates for novel
      therapeutic approaches.

PMID- 15976174
TI  - Genetic interaction of Lobe with its modifiers in dorsoventral patterning and
      growth of the Drosophila eye.
AB  - Dorsoventral (DV) patterning is essential for growth of the Drosophila eye.
      Recent studies suggest that ventral is the default state of the early eye, which
      depends on Lobe (L) function, and that the dorsal fate is established later by
      the expression of the dorsal selector gene pannier (pnr). However, the mechanisms
      of regulatory interactions between L and dorsal genes are not well understood.
      For studying the mechanisms of DV patterning in the early eye disc, we performed
      a dominant modifier screen to identify additional genes that interact with L. The
      criterion of the dominant interaction was either enhancement or suppression of
      the L ventral eye loss phenotype. We identified 48 modifiers that correspond to
      16 genes, which include fringe (fng), a gene involved in ventral eye patterning,
      and members of both Hedgehog (Hh) and Decapentaplegic (Dpp) signaling pathways,
      which promote L function in the ventral eye. Interestingly, 29% of the modifiers
      (6 enhancers and 9 suppressors) identified either are known to interact
      genetically with pnr or are members of the Wingless (Wg) pathway, which acts
      downstream from pnr. The detailed analysis of genetic interactions revealed that
      pnr and L mutually antagonize each other during second instar of larval
      development to restrict their functional domains in the eye. This time window
      coincides with the emergence of pnr expression in the eye. Our results suggest
      that L function is regulated by multiple signaling pathways and that the mutual
      antagonism between L and dorsal genes is crucial for balanced eye growth.

PMID- 15976176
TI  - IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease.
AB  - Interleukin-2 (IL-2) and IL-15 are structurally related cytokines that share
      receptor components but display markedly different effects in multiple in vivo
      model systems. Here we demonstrate that IL-15 but not IL-2 exacerbates xenogeneic
      graft-versus-host disease (X-GVHD) in severe combined immunodeficient murine
      recipients of human peripheral-blood lymphocytes (hu-PBL-SCID). Treatment of hu
      PBL-SCID mice with IL-15 resulted in rapid fatality, lymphocytic infiltrations in
      the liver, lung, and spleen consistent with X-GVHD, and a marked expansion of
      human CD4+ and CD8+ T cells compared with controls. Depletion of human T cells in
      vivo abrogated the lethality of IL-15 treatment. To our knowledge, these data are
      the first to demonstrate in vivo activation and expansion of human T lymphocytes
      in response to IL-15 with concomitant exacerbation of human T-cell-mediated X
      GVHD.

PMID- 15976177
TI  - Human herpesvirus 8 enhances human immunodeficiency virus replication in acutely
      infected cells and induces reactivation in latently infected cells.
AB  - Human herpesvirus 8 (HHV-8) is etiologically associated with Kaposi sarcoma (KS),
      the most common AIDS-associated malignancy. Previous results indicate that the
      HHV-8 viral transactivator ORF50 interacts synergistically with Tat protein in
      the transactivation of human immunodeficiency virus (HIV) long terminal repeat
      (LTR), leading to increased cell susceptibility to HIV infection. Here, we
      analyze the effect of HHV-8 infection on HIV replication in monocyte-macrophage
      and endothelial cells, as potential targets of coinfection. Primary or
      transformed monocytic and endothelial cells were infected with a cell-free HHV-8
      inoculum and subsequently infected with lymphotropic or monocytotropic strains of
      HIV. The results show that HHV-8 coinfection markedly increases HIV replication
      in both cell types. HHV-8 infection induces also HIV reactivation in chronically
      infected cell lines and in peripheral blood mononuclear cells (PBMCs) from
      patients with asymptomatic HIV, suggesting the possibility that similar
      interactions might take place also in vivo. Furthermore, coinfection is not an
      essential condition, since contiguity of differently infected cells is sufficient
      for HIV reactivation. The results suggest that HHV-8 might be a cofactor for HIV
      progression and that HHV-8-infected endothelial cells might play a relevant role
      in transendothelial HIV spread.

PMID- 15976179
TI  - Persistent B19 infection in immunocompetent individuals: implications for
      transfusion safety.
AB  - Recent reports suggested that parvovirus B19 (B19) might persist in
      immunocompetent individuals such as blood donors, but only cross-sectional data
      were available. Serial samples from a cohort of multitransfused patients with
      hemoglobinopathies and a cross-sectional population of pregnant women were tested
      for B19 markers. Of 76 red cell recipients, 6 (8%) had persistent viral DNA for 1
      to 3 or more years, depending on the sensitivity of the genomic amplification
      assay. All patients also carried B19-specific immunoglobulin G (IgG). In
      contrast, 0.8% of 500 pregnant women carried both detectable B19 DNA and specific
      IgG. These results demonstrate that persistence of low levels of B19 DNA
      suggested by cross-sectional studies is frequent in multitransfused patients and
      that the virus may remain detectable several years after infection in
      nonimmunodeficient individuals.

PMID- 15976178
TI  - Dose-dependent effects of the Notch ligand Delta1 on ex vivo differentiation and
      in vivo marrow repopulating ability of cord blood cells.
AB  - Although significant advances have been made over the last decade with respect to
      our understanding of stem cell biology, progress has been limited in the
      development of successful techniques for clinically significant ex vivo expansion
      of hematopoietic stem and progenitor cells. We here describe the effect of Notch
      ligand density on induction of Notch signaling and subsequent cell fate of human
      CD34+CD38- cord blood progenitors. Lower densities of Delta1(ext-IgG) enhanced
      the generation of CD34+ cells as well as CD14+ and CD7+ cells, consistent with
      early myeloid and lymphoid differentiation, respectively. However, culture with
      increased amounts of Delta1(ext-IgG) induced apoptosis of CD34+ precursors
      resulting in decreased cell numbers, without affecting generation of CD7+ cells.
      RNA interference studies revealed that the promotion of lymphoid differentiation
      was primarily mediated by Delta1 activation of Notch1. Furthermore, enhanced
      generation of NOD/SCID repopulating cells was seen following culture with lower
      but not higher densities of ligand. These studies indicate critical, quantitative
      aspects of Notch signaling in affecting hematopoietic precursor cell-fate
      outcomes and suggest that density of Notch ligands in different organ systems may
      be an important determinant in regulating cell-fate outcomes. Moreover, these
      findings contribute to the development of methodology for manipulation of
      hematopoietic precursors for therapeutic purposes.

PMID- 15976180
TI  - Platelet NAD(P)H-oxidase-generated ROS production regulates alphaIIbbeta3
      integrin activation independent of the NO/cGMP pathway.
AB  - Platelets play a crucial role in the physiology of primary hemostasis and
      pathophysiologic processes such as arterial thrombosis. Accumulating evidence
      suggests a role of reactive oxygen species (ROSs) in platelet activation. Here we
      show that platelets activated with different agonists produced intracellular
      ROSs, which were reduced by reduced nicotinamide adenine dinucleotide (phosphate)
      (NAD(P)H) oxidase inhibitors and superoxide scavengers. In addition, we
      demonstrate that ROSs produced in platelets significantly affected alphaIIbbeta3
      integrin activation but not alpha and dense granule secretion and platelet shape
      change. Thrombin-induced integrin alphaIIbbeta3 activation was significantly
      decreased after pretreatment of platelets with NAD(P)H oxidase inhibitors
      (diphenylene iodonium [DPI] [45% +/- 9%] and apocynin [43% +/- 11%]) and
      superoxide scavengers (tiron [60% +/- 9%] and Mn(III)tetrakis (1-methyl-4
      pyridyl)porphyrin [MnTMPyP] [70% +/- 6%]). These inhibitors also reduced platelet
      aggregation and thrombus formation on collagen under high shear and achieved
      their effects independent of the nitric oxide/cyclic guanosine monophosphate
      (NO/cGMP) pathway.

PMID- 15976182
TI  - Membrane-bound and soluble IL-15/IL-15Ralpha complexes display differential
      signaling and functions on human hematopoietic progenitors.
AB  - Membrane-bound and soluble interleukin-15 (IL-15)/IL-15 receptor alpha (Ralpha)
      complexes trigger differential transcription factor activation and functions on
      human hematopoietic progenitors. Indeed, human spleen myofibroblasts (SMFs) are
      characterized by a novel mechanism of IL-15 trans-presentation (SMFmb [membrane
      bound]-IL-15), based on the association of an endogenous IL-15/IL-15Ralpha
      complex with the IL-15Rbetagamma c chains. SMFmb-IL-15 (1) induces lineage
      specific signaling pathways that differ from those controlled by soluble IL-15 in
      unprimed and committed normal progenitors; (2) triggers survival and
      proliferation of leukemic progenitors expressing low-affinity IL-15R (M07Sb
      cells); (3) causes only an antiapoptotic effect on leukemic cells expressing high
      affinity receptors (TF1beta cells). This behavior is likely due to the IL
      15Ralpha chain present on these cells that interact with the SMFmb-IL-15,
      inhibiting signal transducer and transcriptional activator 5 (STAT5) activation.
      On the other hand, the soluble IL-15/IL-15Ralpha complex (hyper IL-15) displays a
      dominant pattern of action, activating only those cells expressing low-affinity
      IL-15R (IL-15Rbetagamma c). Thus, hyper IL-15 induces antiapoptotic effects on
      M075b cells and the up-regulation of STAT6 activation on adult peripheral blood
      (PB) pre-natural killer (NK) committed progenitors. The latter effect using 100
      fold concentrations of recombinant (r)-IL-15. In conclusion, SMFmb-IL-15 and
      soluble IL-15Ralpha/IL-15 complexes seem to play a pivotal role in the control of
      the survival, proliferation and differentiation of both normal and leukemic
      circulating progenitors, highlighting new functions of IL-15 and of IL-15Ralpha.

PMID- 15976181
TI  - Systemic administration of a TLR7 ligand leads to transient immune incompetence
      due to peripheral-blood leukocyte depletion.
AB  - Toll-like receptor (TLR) ligands lead to the induction of proinflammatory
      cytokines and are potent enhancers of specific immune responses. We show here
      that a single systemic dose of R-848, a ligand for TLR7, potently enhanced hapten
      sensitization during the induction of contact hypersensitivity (CHS). However, R
      848 administration also resulted in a rapid and almost complete depletion of
      leukocytes from the blood. This effect was transient and was associated with
      general induction of endothelial adhesiveness. In response to R-848, endothelial
      cells up-regulated adhesion molecules in vitro and in vivo and leukocytes
      exhibited increased rolling on endothelia in R-848-treated animals. Adhesion
      molecule induction appeared to be a direct effect, because endothelial cells
      expressed TLR7 in vitro and in vivo. After R-848 treatment, the tissue residence
      time of leukocytes was markedly prolonged in all major peripheral organs. The
      resulting transiently reduced availability of peripheral-blood leukocytes (PBLs)
      (TRAP) significantly inhibited otherwise potent CHS responses until the effector
      cells returned. Thus, although TLR7 ligands are effective adjuvants for the
      induction of cell-mediated immunity, they can transiently inhibit the elicitation
      of localized immune responses, possibly due to a systemic endothelial activation
      throughout the vasculature.

PMID- 15976184
TI  - Comparison of non-human primate and human whole blood tissue gene expression
      profiles.
AB  - Gene expression profiling is an important tool in the development of medical
      countermeasures against chemical warfare agents (CWAs). Non-human primates
      (NHPs), specifically the rhesus macaque (Macaca mulatta), the cynomologus macaque
      (Macaca fascicularis), and the African green monkey (Chlorocebus aethiops), are
      vital models in the development of CWA prophylactics, therapeutics, and
      diagnostics. However, gene expression profiling of these NHPs is complicated by
      the fact their genomes are not completely sequenced, and that no commercially
      available oligonucleotide microarrays (genechips) exist. We, therefore, sought to
      determine whether gene expression profiling of NHPs could be performed using
      human genechips. Whole blood RNA was isolated from each species and used to
      generate genechip probes. Hybridization of the NHP samples to human genechips
      (Affymetrix Human U133 Plus 2.0) resulted in comparable numbers of transcripts
      detected compared with human samples. Statistical analysis revealed intraspecies
      reproducibility of genechip quality control metrics; interspecies comparison
      between NHPs and humans showed little significant difference in the quality and
      reproducibility of data generated using human genechips. Expression profiles of
      each species were compared using principal component analysis (PCA) and
      hierarchical clustering to determine the similarity of the expression profiles
      within and across the species. The cynomologus group showed the least
      intraspecies variability, and the human group showed the greatest intraspecies
      variability. Intraspecies comparison of the expression profiles identified probe
      sets that were reproducibly detected within each species. Each NHP species was
      found to be dissimilar to humans; the cynomologus group was the most dissimilar.
      Interspecies comparison of the expression profiles revealed probe sets that were
      reproducibly detected in all species examined. These results show that human
      genechips can be used for expression profiling of NHP samples and provide a
      foundation for the development of tools for comparing human and NHP gene
      expression profiles.

PMID- 15976183
TI  - The polysaccharide antibody response after Streptococcus pneumoniae vaccination
      is differentially enhanced or suppressed by 3,4-dichloropropionanilide and 2,4
      dichlorophenoxyacetic acid.
AB  - Propanil (3,4-dichloropropionanilide) and 2,4-D (2,4-dichlorophenoxyacetic acid)
      are commonly used herbicides that have toxic effects on the immune system. The
      present study determined the effect of exposure to these chemicals on the immune
      response to a bacterial vaccine. The antibody responses to the T-independent type
      2 antigen, phosphorylcholine (PC) and the T-dependent antigen, pneumococcal
      surface protein A (PspA) were characterized in C57BL/6 mice after heat-killed
      Streptococcus pneumoniae (HKSP) immunization and single or mixture herbicide
      exposure. Propanil exposure significantly increased the number of PC-specific
      IgM, IgG2b, and IgG3 antibody-secreting B cells (ASC) in the spleen 4-6-fold over
      control animals in a dose-dependent manner. However, the number of ASC in the
      bone marrow and serum titers were comparable in control and propanil-treated
      mice. In contrast, 2,4-D exposure decreased the number of PC-specific IgM and IgG
      bone marrow ASC 2-3-fold from control animals. The decrease in bone marrow ASC in
      2,4-D-treated mice corresponded to a 3-4-fold decrease in PC-specific IgM, IgG2b,
      and IgG3 serum titers compared to control mice. The number of ASC in the spleens
      of 2,4-D-treated mice was, however, comparable to control mice. The antibody
      response to PspA was not affected by any of the treatments. There were no mixture
      interactions between the two herbicides in any of the responses measured. These
      results characterize the primary PC-specific antibody response in the bone
      marrow, spleen, and serum after HKSP vaccination and herbicide exposure. The
      differential effects of propanil and 2,4-D on the antibody response to a
      bacterial vaccine demonstrate the potential of chemical exposure to augment or
      suppress immune responses to vaccines and infectious diseases.

PMID- 15976185
TI  - Momentary brain concentration of trichloroethylene predicts the effects on rat
      visual function.
AB  - The relationship between the concentration of trichloroethylene (TCE) in the
      brain and changes in brain function, indicated by the amplitude of steady-state
      pattern-elicited visual evoked potentials (VEP), was evaluated in Long-Evans
      rats. VEPs were recorded from visual cortex following stimulation of the eyes
      and, thus, reflect the function of the afferent visual pathway and, in broad
      terms, may be indicative of overall brain function. The concentration of TCE in
      the brain at the time of VEP testing (i.e., momentary brain concentration) was
      hypothesized to predict the amplitude of the VEP across a range of inhalation
      concentrations, both during and after exposure. Awake restrained rats were
      exposed to clean air or TCE in the following combinations of concentration and
      duration: 500 ppm (4 h), 1000 ppm (4 h), 2000 (2 h), 3000 ppm (1.3 h), 4000 ppm
      (1 h), and 5000 ppm (0.8 h). VEPs were recorded several times during the exposure
      session, and afterward for experimental sessions of less than 4 h total duration
      (i.e., concentrations from 2000 to 5000 ppm). The sample collection time for each
      VEP was about 1 min. Brain concentrations of TCE were predicted using a
      physiologically based pharmacokinetic (PBPK) model. VEP waveforms were submitted
      to spectral analysis, and the amplitude of the largest response component,
      occurring at twice the temporal stimulation rate (F2), was measured. Exposure to
      all air concentrations of TCE in the study reduced F2 amplitude. The reduction of
      F2 amplitude was proportional to momentary brain TCE concentration during and
      after exposure. A logistical function fit to the combined data from all exposure
      conditions described a statistically significant relationship with 95% confidence
      limits between brain TCE concentration and F2 amplitude. The results support the
      hypothesis that momentary brain concentration of TCE is an appropriate dose
      metric to describe the effects of acute TCE inhalation exposure on rat VEPs. The
      combination of the PBPK model predicting brain TCE concentration from the
      exposure conditions with the logistical function predicting F2 amplitude from the
      brain TCE concentration constitute a quantitative exposure-dose-response model
      describing an acute change in neurological function following exposure to an
      important hazardous air pollutant.

PMID- 15976186
TI  - Induction of the protective antioxidant response element pathway by 6
      hydroxydopamine in vivo and in vitro.
AB  - Parkinson's disease, a progressive neurodegenerative disorder, is characterized
      by loss of midbrain dopaminergic neurons. The etiology of sporadic Parkinson's
      disease is unknown; however, oxidative stress is thought to play a major role in
      disease pathogenesis. Little is known regarding the transcriptional changes that
      occur in Parkinson's disease. The antioxidant response element is a cis-acting
      enhancer sequence that is upstream of many phase II detoxification and
      antioxidant genes. Here we show that 6-hydroxydopamine, a mitochondrial inhibitor
      used to model Parkinson's disease, activates the antioxidant response element
      both in cultured neurons and in the striatum and brainstem of 6-OHDA-lesioned
      mice. Pretreatment with antioxidants or NMDA receptor antagonists reduced but did
      not abolish activation. Further induction of this pathway with tert
      butylhydroquinone was able to significantly reduce cell death due to 6-OHDA in
      vitro. These observations indicate that 6-OHDA activates the antioxidant response
      element through components of oxidative stress, excitotoxicity, and potential
      structural factors. Further induction of this endogenous defense mechanism may
      suggest a novel therapeutic venue in Parkinson's disease.

PMID- 15976187
TI  - Workshop proceedings: managing conflict of interest in science. A little
      consensus and a lot of controversy.
AB  - There is no doubt that participants in the Conflict of Interest (COI) Workshop at
      the Society of Toxicology (SOT) 2005 Annual Meeting (New Orleans, 6-10 March
      2005) engaged in a vigorous and useful exchange of diverse ideas and viewpoints.
      While there was consensus on the value and interest of this Workshop, there was
      less consensus and more controversy over many of the issues discussed during the
      Workshop, which included the distinction between bias and conflict, the success
      or failure of policies of disclosure, whether waivers should or should not be
      granted to conflicted individuals in order to seat a "balanced" committee with
      appropriate expertise, whether conflicted individuals retain the ability to
      recognize their own conflict, and more. The discussion left no doubt, however,
      that conflict of interest will remain an important and controversial issue in the
      scientific community for some time to come.

PMID- 15976188
TI  - Perinatal lipopolysaccharide exposure downregulates pregnane X receptor and
      Cyp3a11 expression in fetal mouse liver.
AB  - The pregnane X receptor (PXR) is a member of the nuclear receptor superfamily
      that regulates cytochrome P450 3A (CYP3A) gene transcription in a ligand
      dependent manner. Lipopolysaccharide (LPS)-induced downregulation on PXR and
      cyp3a11 in adult mouse liver has been well characterized. In this study, we
      investigated the effects of maternal LPS exposure on PXR and cyp3a11 expression
      in fetal mouse liver. Pregnant ICR mice were injected intraperitoneally with
      different doses of LPS (0.1 approximately 0.5 mg/kg) on gestational day (GD) 17.
      PXR and cyp3a11 mRNA levels were determined using RT-PCR. Erythromycin N
      demethylase (ERND) activity was used as an indicator of CYP3A expression in this
      study. Results showed that LPS significantly downregulated PXR and cyp3a11 mRNA
      levels and ERND activity in fetal liver in a dose-dependent manner. LPS-induced
      downregulation of PXR and cyp3a11 mRNA expression and ERND activity was
      attenuated after pregnant mice were pretreated with alpha-phenyl-N-t-butylnitrone
      (PBN), a free radical spin trapping agent. Additional experiment revealed that
      LPS significantly increased lipid peroxidation in fetal liver, which was also
      attenuated by PBN pretreatment. Furthermore, LPS-induced downregulation of PXR
      and cyp3a11 mRNA expression and ERND activity was prevented by maternal
      pretreatment with N-acetylcysteine (NAC). Maternal pretreatment with NAC also
      inhibited LPS-initiated lipid peroxidation and GSH depletion in fetal liver.
      However, maternal LPS treatment did not affect nitrite plus nitrate concentration
      in fetal liver. Correspondingly, aminoguanidine, a selective inhibitor of
      inducible nitric oxide synthase (iNOS), has no effect on LPS-induced
      downregulation of PXR and cyp3a11 expression and ERND activity in fetal liver.
      These results indicated that maternal LPS exposure downregulates PXR and cyp3a11
      in fetal mouse liver. Reactive oxygen species (ROS) may be involved in LPS
      induced downregulation of PXR and cyp3a11 in fetal mouse liver.

PMID- 15976189
TI  - The diverse actions of nicotine and different extracted fractions from tobacco
      smoke against hapten-induced colitis in rats.
AB  - The etiology of ulcerative colitis (UC) remains unknown, although the risk of
      developing UC is apparently higher in non-smokers and ex-smokers. We have
      demonstrated in a colitis animal model that exposure to tobacco smoke could
      attenuate UC pathogenesis. The present study aimed to investigate and compare
      between the modes of action of nicotine and different fractions of tobacco smoke
      extract in the development of experimental colitis. The hapten 2,4-dinitrobenzene
      sulfonic acid (DNBS) was used to induce colitis in Sprague-Dawley rats. Results
      indicated that both tobacco smoke exposure and subcutaneous nicotine
      differentially reduced colonic lesion size, myeloperoxidase (MPO) activity,
      luminol-amplified free radical generation, and leukotriene B4 formation in the
      inflamed colon of colitis animals. These phenomena were accompanied by the
      downregulation of colonic interleukin (IL)-1beta and monocyte chemoattractant
      protein (MCP)-1 protein expression. By treating the colitis animals with various
      tobacco extracts, we further discovered that ethanol extract from filtered
      tobacco smoke could attenuate DNBS-evoked colonic damage and the elevated MPO
      activity, while at the same time it downregulated colonic IL-1beta and MCP-1
      protein expression. In contrast, the highest dose of the chloroform extract from
      the cigarette filter caused aggravating effects and overexpression of the pro
      inflammatory cytokines and chemokines. These data suggest that effective
      attenuation of DNBS-induced colitis by tobacco smoke could be due to its nicotine
      content and possibly other flavonoid components found in the ethanol smoke
      extract.

PMID- 15976190
TI  - Post-intoxication vaccination for protection of neurons against the toxicity of
      nerve agents.
AB  - Nerve agents are highly toxic organophosphates (OPs) that can cause severe damage
      to the central and peripheral nervous systems. The central nervous system insult
      results in seizures and neuronal death. The glutamatergic system apparently
      contributes to the neuropathology. Using a model of OP intoxication causing death
      of retinal ganglion cells in the mouse eye, we show here that intoxication is
      exacerbated if the mice are devoid of mature T cells. The retinal neurons could
      be protected from these effects by vaccination, 7 days before or immediately
      after intoxication, with the copolymer glatiramer acetate (Cop-1), recently found
      to limit the usual consequences of an acute glutamate insult to the eye. These
      findings underlie a new therapeutic approach to protection against OP
      intoxication, based on the rationale that boosting of the adaptive immunity
      recruited at the site of intoxication helps the local cellular machinery such as
      resident microglia to withstand the neurotoxic effects.

PMID- 15976191
TI  - Issues in risk assessment for developmental effects of 2,3,7,8-tetrachlorodibenzo
      p-dioxin and related compounds.
AB  - Recent risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      related compounds have focused on adverse effects observed in rodent offspring
      exposed while in utero during critical gestational periods as among the most
      sensitive adverse effects attributable to TCDD exposure. In addition, these risk
      assessments have converged on the use of body concentration (or "body burden") of
      TCDD as a dose metric superior to administered dose for cross-species comparisons
      and risk assessments, due to the interspecies differences in elimination kinetics
      and substantial persistence of these compounds. The detailed, although
      incomplete, data that are available on maternal-fetal distribution of TCDD and
      related compounds illustrate differences in distribution among these compounds
      that impact assessments on a body-burden basis. These data also demonstrate
      differences in distribution after subchronic or chronic administration compared
      to acute administration. Some data are now also available addressing
      inconsistencies that may arise from the use of TCDD toxic equivalency factors
      (TEFs), which were derived on an administered-dose basis, in evaluating responses
      to mixtures of dioxins on a body-burden basis in the context of chronic exposure
      situations. Finally, the use of body burden as a dose metric does not account for
      or eliminate the substantial differences in sensitivity to dioxin observed across
      species or between different strains of the same species and, thus, does not
      eliminate the need to consider the relative sensitivity of humans compared to
      laboratory animal models in risk assessments. Additional research areas that may
      increase the foundation for interspecies extrapolations are discussed.

PMID- 15976192
TI  - Relationship between hepatic gene expression profiles and hepatotoxicity in five
      typical hepatotoxicant-administered rats.
AB  - In the field of gene expression analysis, DNA microarray technology has a major
      impact on many different areas including toxicogenomics, such as in predicting
      the adverse effects of new drug candidates and improving the process of risk
      assessment and safety evaluation. In this study, we investigated whether there is
      relationship between the hepatotoxic phenotypes and gene expression profiles of
      hepatotoxic chemicals measured by DNA microarray analyses. Sprague-Dawley rats (6
      weeks old) were administered five hepatotoxicants: acetaminophen (APAP),
      bromobenzene, carbon tetrachloride, dimethylnitrosamine, and thioacetamide. Serum
      biochemical markers for liver toxicity were measured to estimate the maximal
      toxic time of each chemical. Hepatic mRNA was isolated, and the gene expression
      profiles were analyzed by DNA microarray containing 1,097 drug response genes,
      such as cytochrome P450s, other phase I and phase II enzymes, nuclear receptors,
      signal transducers, and transporters. All the chemicals tested generated specific
      gene expression patterns. APAP was sorted to a different cluster from the other
      four chemicals. From the gene expression profiles and maximal toxic time
      estimated by serum biochemical markers, we identified 10 up-regulated genes and
      10 down-regulated genes as potential markers of hepatotoxicity. By Quality
      Threshold (QT) clustering analysis, we identified major up- and down-regulated
      expression patterns in each group. Interestingly, the average gene expression
      patterns from the QT clustering were correlated with the mean value profiles from
      the biochemical markers. Furthermore, this correlation was observed at any extent
      of hepatotoxicity. In this study, we identified 17 potential toxicity markers,
      and those expression profiles could estimate the maximal toxic time independently
      of the hepatotoxicity levels. This expression profile analysis could be one of
      the useful tools for evaluating a potential hepatotoxicant in the drug
      development process.

PMID- 15976193
TI  - Induction of competing apoptotic and survival signaling pathways in the
      macrophage by the ribotoxic trichothecene deoxynivalenol.
AB  - Deoxynivalenol (DON) and other ribotoxic trichothecenes cause immune stimulation
      and suppression in leukocytes by upregulating gene expression and apoptosis,
      respectively. The purpose of this study was to test the hypothesis that MAPKs
      mediate both apoptosis and survival in DON-exposed macrophages. At concentrations
      which partially inhibit translation, DON induced phosphorylation of p38 and ERK
      1/2 mitogen activated protein kinases within 15 min in RAW 264.7 macrophages and
      these effects lasted up to 3 h. DON-exposed cells exhibited marked caspase 3
      dependent DNA fragmentation after 6 h which was suppressed and attenuated by the
      p38 inhibitor SB203580 and ERK inhibitor PD98059, respectively. DON readily
      induced the phosphorylation and activity of p53 and this was inhibitable by
      SB203580. DON exposure evoked BAX translocation to mitochondria and corresponding
      cytochrome C release but did not alter mitochondrial membrane potential. The p53
      inhibitor PFTalpha reduced both DON-induced phosphorylation of p53 and p53
      binding activity. Moreover, both PFTalpha and p53 siRNA transfection suppressed
      DON-induced caspase-3 activity and subsequent DNA fragmentation. Concurrent with
      p53 activation, DON activated two anti-apoptotic survival pathways as evidenced
      by both ERK-dependent p90 Rsk and AKT activation. Taken together, the results
      indicate that DON initiates competing apoptotic (p38/p53/Bax/Mitochondria/Caspase
      3) and survival (ERK/AKT/p90Rsk/Bad) pathways in the macrophage.

PMID- 15976194
TI  - Estrogen-induced abnormal accumulation of fat cells in the rat penis and
      associated loss of fertility depends upon estrogen exposure during critical
      period of penile development.
AB  - We previously reported that diethylstilbestrol (DES) or estradiol valerate (EV)
      exposure at a dose of 0.10-0.12 mg/kg, or higher, per day, on alternate days,
      from postnatal days 2-12, resulted in abnormal penis development and infertility
      (H. O. Goyal et al., 2005, J. Androl. 26, 32-43). The objective of this study was
      to identify a critical developmental period(s) during which EV exposure results
      in the observed penile abnormalities. Male pups received EV at a dose of 0.10
      0.12 mg/kg on postnatal day(s) 1, 1-3, 4-6, 1-6, 7-12, 13-18, 19-24, or 25-30.
      Fertility was tested at 102-115 days of age and tissues were examined at 117-137
      days. Both penile morphology and fertility were unaltered in rats treated with EV
      after 12 days of age. Conversely, except in rats treated on postnatal day 1 only,
      none of the males treated prior to 12 days of age sired pups, and all had
      abnormal penises, including varying degrees of abnormal accumulation of fat cells
      and loss of cavernous spaces and smooth muscle cells in the corpora cavernosa
      penis, which were maximal in the 1-6-day group. Also, the preputial sheath was
      partially released or its release was delayed, and the weight of the
      bulbospongiosus muscle was significantly reduced. Plasma testosterone (T) in the
      1-6- and 4-6-day groups and intratesticular T in the 4-6-day group were
      significantly lower. The testosterone surge, characteristic of controls in the
      first week of life, was suppressed in the 1-3-day group. Estrogen receptor alpha
      mRNA expression was enhanced in the body of the penis in the 1-3-day group, but
      not in the 13-18-day group. Hence, EV exposure prior to 12 days of age (as short
      as 1-3 days postnatal), but not after 12 days of age, results in long-term
      abnormal penile morphology, characterized by abnormal accumulation of fat cells
      in the corpora cavernosa penis and, consequently, loss of fertility.

PMID- 15976195
TI  - Composition, toxicity, and mutagenicity of particulate and semivolatile emissions
      from heavy-duty compressed natural gas-powered vehicles.
AB  - Particulate matter (PM) and vapor-phase semivolatile organic compounds (SVOC)
      were collected from three buses fueled by compressed natural gas. The bus engines
      included a well-functioning, conventional engine; a "high emitter" engine; and a
      new technology engine with an oxidation catalyst. Chemical analysis of the
      emissions showed differences among these samples, with the high emitter sample
      containing markers of engine oil constituents. PM + SVOC samples were also
      collected for mutagenicity and toxicity testing. Extraction efficiencies from the
      collection media were lower than for similarly collected samples from gasoline or
      diesel vehicles. Responses to the recovered samples were compared on the basis of
      exhaust volume, to incorporate the emission rates into the potency factors.
      Mutagenicity was assessed by Salmonella reverse mutation assay. Mutagenicity was
      greatest for the high emitter sample and lowest for the new technology sample.
      Metabolic activation reduced mutagenicity in strain TA100, but not TA98.
      Toxicity, including inflammation, cytotoxicity, and parenchymal changes, was
      assessed 24 h after intratracheal instillation into rat lungs. Lung responses
      were generally mild, with little difference between the responses to equivalent
      volumes of emissions from the normal emitter and the new technology, but greater
      responses for the high emitter. These emission sample potencies are further
      compared on the basis of recovered mass with previously reported samples from
      normal and high-emitter gasoline and diesel vehicles. While mutagenic potencies
      for the CNG emission samples were similar to the range observed in the gasoline
      and diesel emission samples, lung toxicity potency factors were generally lower
      than those for the gasoline and diesel samples.

PMID- 15976196
TI  - Temporal integration of nasal irritation from ammonia at threshold and supra
      threshold levels.
AB  - Two experiments examined integration of perceived irritation over short-term
      (approximately 100-4000 ms) delivery of ammonia into the nasal cavity of human
      subjects. Experiment 1 examined trade-offs between time and concentration at
      threshold level by means of nasal lateralization, a common measure of irritation
      threshold. Within experimental sessions, the duration of a fixed-concentration
      stimulus varied to determine the shortest, detectable pulse. Subjects could
      lateralize increasingly weaker concentrations with longer stimulus presentations.
      Experiment 2 examined an analogous trade-off for supra-threshold irritation.
      Subjects rated irritation from presentations of ammonia that varied both in
      concentration and in duration. Rated intensity for a given concentration
      increased with stimulus duration. Hence integration occurred at both threshold
      and supra-threshold levels. However, more than a twofold increase in duration was
      required to compensate for a twofold decrease in concentration to maintain
      threshold lateralization or a fixed level of perceived intensity. These results
      suggest that an imperfect mass-integrator model may be able to describe short
      term integration of nasal irritation from ammonia at both the threshold and supra
      threshold levels.

PMID- 15976197
TI  - Hemodynamic changes during off-pump coronary artery bypass anastomosis in
      patients with coexisting mitral regurgitation: improvement with milrinone.
AB  - We hypothesized that mitral regurgitation (MR) would be exacerbated, cardiac
      index (CI) decreased, and mean pulmonary artery pressure (MPAP) increased in
      patients with coexisting MR during off-pump coronary artery bypass (OPCAB)
      anastomosis, and that milrinone could ameliorate increases in MR that occur
      during OPCAB anastomosis. Subjects comprised 140 patients scheduled for elective
      OPCAB divided into three groups: patients without MR (MR(-) group; n = 57),
      patients with MR (MR(+) group; n = 41), and patients with MR who received
      milrinone (M+MR(+) group; n = 42). Patients with grade 1+ or 2+ MR were included,
      whereas those with grade 3+ or 4+ MR were excluded. Hemodynamic variables were
      measured after the induction of anesthesia and during anastomosis. IV infusion of
      milrinone (0.5 microg . kg(-1) . min(-1)) started immediately after the induction
      of anesthesia in the M+MR(+) group. CI was significantly decreased (P < 0.0001),
      and MPAP and MR were significantly increased (P < 0.001) during left coronary
      anastomosis in the MR(+) group compared with the MR(-) group. CI was
      significantly higher (P < 0.001), and neither MPAP nor MR were increased (P <
      0.05) during left coronary artery anastomosis in the M+MR(+) group compared to
      the MR(+) group. In patients with MR, anastomosis of the left coronary artery
      branches was associated with decreased CI and increased regurgitation and MPAP.
      In such patients, treatment with milrinone helps to stabilize hemodynamics during
      anastomosis.

PMID- 15976198
TI  - Both milrinone and colforsin daropate attenuate the sustained pial arteriolar
      constriction seen after unclamping of an abdominal aortic cross-clamp in rabbits.
AB  - We previously reported that unclamping of an abdominal aortic cross-clamp causes
      initial dilation of pial arteries followed by sustained constriction. Both
      milrinone and colforsin daropate have a vasodilator action, and both have been
      used in such critical conditions as abdominal aortic aneurysmectomy. We measured
      cerebral pial arteriolar diameters using a rabbit closed cranial window
      preparation before (baseline) and 15 min after the start of an IV infusion of
      0.9% saline (control group), milrinone, or colforsin daropate (0.05 and 0.5
      microg . /kg(-1) . min(-1)) (pre-clamp), just after aortic clamping, 20 min after
      clamping, and at 0 to 60 min after unclamping. In the control group, a
      significant decrease in diameter persisted for at least 60 min after unclamping
      (maximum, -15% for large and -26% for small arterioles versus baseline). These
      values were significantly smaller after both doses of milrinone and the larger
      dose of colforsin daropate (-5% and -8%, 10% and 12%, and -2% and -5%,
      respectively vs baseline, at 60 min). In a second experiment, changes in regional
      cerebral blood flow and tissue oxygen tension reflected changes in vascular
      variables. Thus, sustained cerebral pial arteriolar constriction induced by
      aortic unclamping can be attenuated by IV milrinone or colforsin daropate.

PMID- 15976199
TI  - Atrial fibrillation after cardiac surgery/cardiopulmonary bypass is associated
      with monocyte activation.
AB  - Atrial fibrillation (AF) contributes significantly to morbidity and mortality in
      as many as one-third of patients after cardiac surgery that requires
      cardiopulmonary bypass (CPB). Recent data suggest that inflammatory infiltration
      of the myocardium may predispose to AF. We conducted an exploratory pilot study
      to determine if there was an association between the perioperative leukocyte
      inflammatory response to cardiac surgery/CPB and postoperative AF. We enrolled 72
      patients undergoing cardiac surgery with CPB; all patients were in sinus rhythm
      before surgery. Leukocyte activation (CD11b upregulation) was perioperatively
      measured in monocytes and neutrophils (PMN). Preoperative C-reactive protein
      (CRP) and perioperative neutrophil myeloperoxidase (MPO) were also monitored for
      inflammation, and troponin I was assayed for perioperative cardiac muscle damage.
      All markers were evaluated for differences between the subset of patients who
      developed AF versus those who remained in normal sinus rhythm after surgery. All
      72 patients completed the study. Postoperative AF developed in 26 (36%) patients.
      Perioperative monocyte CD11b upregulation was significantly increased in patients
      who developed AF (P = 0.01), but increases in PMN CD11b were not significantly
      associated with AF (P = 0.057). The increase in both monocyte and PMN counts
      after aortic cross-clamp release was significantly associated with postoperative
      AF (P = 0.007 and P = 0.005, respectively). By contrast, preoperative CRP and
      perioperative MPO did not differ between AF and normal rhythm patients.
      Similarly, the peak value of troponin I did not differ between groups. In this
      pilot study of cardiac surgery/CPB patients, perioperative upregulation of the
      monocyte adhesion receptor, CD11b, and higher circulating monocyte and PMN
      numbers were associated with postoperative AF, suggesting that the induction of
      cellular inflammation during cardiac surgery/CPB may contribute to this
      pathophysiology.

PMID- 15976200
TI  - The effect of concomitant radiofrequency ablation and surgical technique (repair
      versus replacement) on release of cardiac biomarkers during mitral valve surgery.
AB  - All patients undergoing heart surgery experience a certain amount of nonspecific
      myocardial injury documented by the release of cardiac biomarkers and associated
      with poor outcome. We investigated the role of unipolar radiofrequency ablation
      of atrial fibrillation on the release of cardiac biomarkers in 71 patients
      undergoing mitral valve surgery and concomitant left atrial ablation case-matched
      with 71 patients undergoing isolated mitral surgery. The study was powered to
      detect a 3 ng/mL difference. There was no difference between the 2 groups in
      terms of cardiac troponin I (10 +/- 5.3 versus 12 + 10.4 ng/mL; P = 0.7) or
      creatine kinase-MB (50 +/- 21.8 versus 57 +/- 62.0 ng/mL; P = 0.5) release.
      Postoperative peak cardiac troponin I levels had univariate associations with the
      duration of cardiopulmonary bypass (P = 0.002) and aortic cross-clamping (P =
      0.001) and with the surgical technique (15 +/- 12 ng/mL for mitral valve
      replacement versus 9 +/- 4.8 for mitral valve repair; P = 0.0007) at univariate
      analysis. Mitral valve replacement was the only independent predictor of
      postoperative peak release of cardiac troponin I identified with multivariate
      analysis (P = 0.005). Radiofrequency ablation of atrial fibrillation does not
      significantly increase cardiac biomarker release compared with isolated mitral
      surgery; mitral valve repair is associated with less release of cardiac
      biomarkers compared with mitral valve replacement.

PMID- 15976201
TI  - A comparison of transfusion requirements between living donation and cadaveric
      donation liver transplantation: relationship to model of end-stage liver disease
      score and baseline coagulation status.
AB  - The use of living donation is an important option for patients in need of liver
      transplant. We retrospectively reviewed the preoperative Model for End-Stage
      Liver Disease (MELD) score, baseline coagulation laboratory results, and
      intraoperative transfusion of red blood cells and component therapy for 27 living
      donation transplants and 69 cadaveric donation transplants during a 3-yr period
      (2001-2004). Patients undergoing living donation transplantation had
      significantly lower MELD scores and preserved coagulation function compared with
      cadaveric donation transplantation recipients (P < 0.001). The living donation
      transplant patients also received significantly fewer transfusions of red blood
      cells and component therapy compared with the cadaveric donation transplant
      patients (P < 0.001). For the combined population of both cadaveric donation
      transplant and living donation transplant patients, there were significant
      associations between MELD score and preoperative coagulation tests (P < 0.001)
      and intraoperative transfusion of blood and component therapy. MELD score and
      preoperative fibrinogen concentration were identified as independent predictors
      of transfusion exposure. In conclusion, we detected significant differences in
      severity of disease at time of transplantation, degree of impairment of
      coagulation function, and need for transfusion of red blood cells and component
      therapy between patients undergoing living donation transplantation compared with
      patients undergoing cadaveric donation transplantation.

PMID- 15976202
TI  - Chest tube suction-associated unilateral negative pressure pulmonary edema in a
      lung transplant patient.
AB  - We describe a 29-yr-old male, status post-bilateral lung transplant, who
      developed unilateral negative pressure pulmonary edema induced by chest tube
      suction in association with bilateral bronchial anastomotic strictures. We
      conclude that negative pressure pulmonary edema may occur secondary to high
      levels of negative pressure applied to the intrapleural space via chest tubes in
      the presence of partial large airway obstruction. Post-lung transplant patients
      may be especially at risk because of compromised lymphatic drainage.

PMID- 15976203
TI  - Moral permissibility as a guide for decision making about conjoined twins.

PMID- 15976204
TI  - Anesthetic management of conjoined twins presenting for palliative open-heart
      surgery.
AB  - A set of dicephalous parapagus twins was born at 36 wk gestational age. Twin A
      had complex congenital heart disease in the form of a single ventricle that would
      be fatal without surgical intervention. Twin B had normal intracardiac anatomy.
      The twins were deemed surgically inseparable and the parents requested palliative
      open-heart surgery on Twin A. The twins shared a common circulatory system to the
      lower half of the body so that physiological manipulations in one twin adversely
      affected the other's hemodynamic condition. Twin A underwent successful single
      ventricle palliation; however, after a prolonged hospitalization, the infants
      died secondary to severe respiratory disease in Twin B.

PMID- 15976205
TI  - A method for measuring system safety and latent errors associated with pediatric
      procedural sedation.
AB  - The practice of sedating patients in the hospital for diagnostic and therapeutic
      procedures may be associated with life-threatening respiratory depression. We
      describe a method that uses a simulated event to identify latent system failures.
      A simulated scenario was developed that was reproducible with realistic
      physiology that degraded over time if no interventions occurred and improved when
      treated appropriately. Management of the scenario was observed in an ideal
      setting, a radiology department, and an emergency department. Event management
      was videotaped. The simulator's physiological data were saved automatically at 5
      s intervals. Deviations from "best practice" were measured by using a set of
      video markers for event detection, diagnosis, and treatment. The simulator data
      files were used to calculate time out of range for critical variables. Hypoxia
      and hypotension lasted 4.5 and 5.5 min in the radiology and emergency
      departments, respectively, compared with 0 min in the gold standard setting. Many
      latent failures were identified by reviewing the video. This study supports the
      feasibility of using available human simulation as a crash-test dummy to more
      objectively quantify rescue system performance in actual sedation care settings.
      This method revealed vulnerabilities in personnel and in care systems even though
      sedation care regulatory requirements were met.

PMID- 15976206
TI  - Ondansetron oral disintegrating tablets: acceptability and efficacy in children
      undergoing adenotonsillectomy.
AB  - Postoperative nausea and vomiting (PONV), a major complication in children, is
      responsive to IV and oral ondansetron. Because these routes are not always
      available, we studied the acceptability and efficacy of ondansetron oral
      disintegrating tablets (ODT). In this double-blind, randomized, placebo
      controlled study, 62 patients undergoing adenotonsillectomy, aged 5 to 11 years,
      preoperatively received ODT (4 mg) or placebo. Patients assessed the medication
      for taste and sensation. Anesthesia was induced with sevoflurane, maintained with
      desflurane, and supplemented with fentanyl 2.5 microg/kg and dexamethasone 0.5
      mg/kg (maximum dose, 12 mg). An observer blinded to treatment evaluated patients
      for pain, agitation, and PONV. Postoperative treatment consisted of fentanyl 1
      microg/kg for pain and agitation and metoclopramide 0.15 mg/kg (maximum dose, 10
      mg) for PONV. There were no significant differences between study groups with
      regard to age, weight, recovery time, agitation, or pain. Approximately 90% of
      the subjects found the ODT to taste good. No subject rejected the study
      medication, but the ondansetron-containing tablets were found to be less
      palatable than the placebo. The incidence of vomiting was significantly less in
      the ondansetron-medicated group.

PMID- 15976207
TI  - Sugar solution analgesia: the effects of glucose on expressed mu opioid
      receptors.
AB  - Glucose or sucrose solutions administered orally provide effective analgesia for
      procedural pain in neonates. Because analgesia with sugar solutions can be
      decreased by opioid receptor antagonists, we tested the hypothesis that glucose
      directly activates opioid receptors. Mu opioid receptors (MOR-1) were expressed
      in Xenopus oocytes, a well recognized expression system, and glucose was tested
      for possible agonist, antagonist, and modulatory effects on the receptor. In
      control experiments, 10 nM of Tyr-D-Ala-Gly-Me-Phe-Gly-ol (DAMGO), a synthetic
      enkephalin and specific mu agonist, activated the MOR-1, whereas 20 mM of glucose
      had no effect. In addition, glucose had no effect on the activation of the mu
      receptor by DAMGO. Finally, glucose did not modulate acute receptor
      desensitization induced by DAMGO. We conclude that glucose does not directly
      interact with MOR-1 in an in vitro expression system and that the purported
      interaction between glucose and the opioid system may be an indirect one,
      involving release of endogenous opioids.

PMID- 15976208
TI  - Caudal additives in pediatrics: a comparison among midazolam, ketamine, and
      neostigmine coadministered with bupivacaine.
AB  - Single-shot "kiddie caudal" with bupivacaine alone is losing popularity because
      of its duration of 4-8 h. In a prospective randomized double-blind clinical
      study, we assessed and compared the efficacy of ketamine, midazolam, and
      neostigmine coadministered with bupivacaine in a caudal epidural to provide
      intraoperative and postoperative pain relief. Eighty children (ASA status I) aged
      5-10 yr undergoing unilateral inguinal herniotomy were allocated randomly in
      equal numbers (n = 20) into 4 groups to receive a caudal injection of 0.25%
      bupivacaine (1 mL/kg) with or without ketamine (0.5 mg/kg), midazolam (50
      microg/kg), and neostig-mine (2 microg/kg), after the induction of standardized
      general anesthesia without premedication. Monitoring for pain, sedation,
      postoperative nausea/vomiting, dizziness, and pruritus was performed by
      anesthesiologists blinded to the study allocation. The time to first analgesic
      administration (paracetamol syrup) was longer (P < 0.05) in the bupivacaine
      neostigmine group and the bupivacaine-midazolam group than in the other groups.
      Undesirable effects, such as emesis, pruritus, and dizziness, were comparable in
      all groups. However, the incidence of hallucination was more frequent in the
      bupivacaine-ketamine group compared with the other groups. This study shows that
      single-shot caudal coadministration of bupivacaine-neostigmine and bupivacaine
      midazolam was associated with an extended duration of postoperative pain relief.

PMID- 15976209
TI  - Bidirectional glenn shunt surgery using lepirudin anticoagulation in an infant
      with heparin-induced thrombocytopenia with thrombosis.
AB  - There are few reports of the management of pediatric patients with heparin
      induced thrombocytopenia (HIT) requiring cardiac surgery using currently
      available anticoagulants. We report a case of an infant with HIT requiring a
      bidirectional Glenn shunt who was successfully managed using lepirudin (r
      hirudin, Refludan; Aventis, Bridgewater, NJ). Dosing and monitoring of
      anticoagulation were difficult, and we suggest caution in the use of lepirudin
      for cardiac surgery unless reliable monitoring of the degree of anticoagulation
      becomes available.

PMID- 15976210
TI  - Spinal anesthesia with hyperbaric levobupivacaine and ropivacaine for outpatient
      knee arthroscopy: a prospective, randomized, double-blind study.
AB  - To compare unilateral spinal block produced with small doses of hyperbaric
      ropivacaine with that produced by 2 doses of hyperbaric levobupivacaine, we
      randomly allocated 91 ASA physical status I-II outpatients undergoing knee
      arthroscopy to receive unilateral spinal anesthesia with 7.5 mg of hyperbaric
      ropivacaine 0.5% (group Ropi-7.5, n = 31) or either 7.5 mg (group Levo-7.5, n =
      30) or 5 mg (group Levo-5, n = 30) of hyperbaric levobupivacaine 0.5%. Spinal
      anesthesia was performed at the L3-4 interspace using a 25-gauge Whitacre spinal
      needle. The lateral decubitus position was maintained for 15 min after injection.
      Strictly unilateral sensory block was present in 73%, 50%, and 61% of cases in
      groups Ropi-7.5, Levo-7.5, and Levo-5, respectively, 30 min after injection (P =
      0.40), and unilateral motor block was observed in 94%, 93%, and 83% in groups
      Ropi-7.5, Levo-7.5, and Levo-5, respectively (P = 0.31). One patient of group
      Ropi-7.5 required general anesthesia to complete surgery, and fentanyl
      supplementation was required in one patient of group Ropi-7.5 (3%) and one
      patient of group Levo-5 (3%) (P = 0.42). The median (range) time for spinal block
      resolution was shorter in group Ropi-7.5 (135 [126-154] min] than in group Levo
      7.5 (162 [148-201] min) (P = 0.04); whereas home discharge was shorter in groups
      Ropi-7.5 (197 [177-218] min) and Levo-5 (197 [187-251] min) as compared with
      group Levo-7.5 (238 [219-277] min) (P = 0.02 and P = 0.04, respectively). We
      conclude that 7.5 mg of 0.5% hyperbaric ropivacaine and 5 mg of 0.5% hyperbaric
      levobupivacaine provide adequate spinal block for outpatient knee arthroscopy,
      with a faster home discharge as compared with 7.5 mg of 0.5% hyperbaric
      levobupivacaine.

PMID- 15976211
TI  - Perioperative rofecoxib plus local anesthetic field block diminishes pain and
      recovery time after outpatient inguinal hernia repair.
AB  - In this study, we compared pain scores after inguinal herniorrhaphy in patients
      treated by preincisional local anesthetic field block (PL), or PL combined with
      perioperative rofecoxib, with controls who received standard care. Seventy-five
      patients having herniorrhaphy under general anesthesia were randomly assigned to
      receive a placebo pill preoperatively, and for 5 days postoperatively (CONT);
      preoperative bupivacaine field block and perioperative placebo (PL); preoperative
      field block plus rofecoxib, 50 mg preoperatively and for 5 days postoperatively
      (PLR). Bupivacaine infiltration in the wound at closure, IV fentanyl and
      acetaminophen/oxycodone were administered postoperatively to all. Discharge time,
      pain scores (0-10), analgesic use, and satisfaction scores (1-6) were compared
      using analysis of variance. PLR patients had lower maximum pain scores (worst
      pain) in the postanesthesia care unit (3.7 versus 5.3, P = 0.02) and at 24 h (5.3
      versus 6.8, P = 0.03), were discharged 38 min sooner (P = 0.01), required 28%
      less oxycodone 0-24 h after discharge (P = 0.04), and reported higher
      satisfaction scores compared with CONT. Pain in PL was less than CONT for 30 min.
      There were no differences among the 3 groups after 24 h postoperatively. We
      conclude that perioperative rofecoxib with PL reduces in-hospital recovery time,
      decreases pain scores and opioid use, and improves satisfaction scores in the
      first 24 h after surgery.

PMID- 15976212
TI  - Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but
      better local safety than its prodrug, propacetamol, for postoperative pain after
      third molar surgery.
AB  - We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion
      with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled,
      double-blind, parallel group trial in patients with moderate-to-severe pain after
      third molar surgery. Treatment efficacy was assessed in house for 6 h after
      starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were
      obtained with both active treatments on pain relief, pain intensity difference on
      a 100-mm visual analog scale, and on a categorical scale (except for propacetamol
      at 6 h). No significant differences were noted between active groups except at 1
      h. Six-hour weighted sums of primary assessments showed significantly better
      efficacy than placebo (P < 0.0001) and no difference between active treatments.
      Median stopwatch time to onset of pain relief for active treatment was 6-8 min
      after infusion start. Active treatments showed comparable efficacy with a
      significantly longer duration of analgesia and better patients' global evaluation
      compared with placebo. The incidence of patients reporting local pain at the
      infusion site was significantly less frequent after IV acetaminophen or placebo
      (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and
      propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a
      more frequent incidence of local pain at the infusion site for propacetamol.

PMID- 15976213
TI  - The different effects of intravenous propofol and midazolam sedation on
      hemodynamic and heart rate variability.
AB  - Heart rate (HR) and arterial blood pressure (BP) changes have been reported
      during conscious sedation with propofol and midazolam. One potential mechanism to
      explain these changes is that propofol and midazolam affect HR and BP via changes
      in the cardiac autonomic nervous system. Two specific hypotheses were tested by
      HR variability analysis: 1) propofol induces predominance of parasympathetic
      activity, leading to decreased HR and BP, and 2) midazolam induces predominance
      of sympathetic activity, leading to increased HR and decreased BP. Thirty dental
      patients were included in a prospective, randomized study. HR, BP, low frequency
      (LF), high frequency (HF), and entropy were monitored during the awake, sedation,
      and recovery periods and depth of sedation was assessed using the Observer's
      Assessment of Alertness/Sedation score. Propofol induced a significant decrease
      in total power (503 +/- 209 ms(2)/Hz versus 162 +/- 92 ms(2)/Hz) and LF/HF ratio
      (2.5 +/- 1.2 versus 1.0 +/- 0.4), despite the absence of any change in HR during
      the sedation period compared with baseline. Midazolam decreased normalized HF (34
      +/- 10% versus 10 +/- 4%) but did not significantly change LF/HF ratio (2.3 +/-
      1.1 versus 2.2 +/- 1.4) and increased HR in the sedation period. Compared with
      baseline, propofol was associated with a significant increase in normalized HF in
      the recovery period (34 +/- 11% versus 44 +/- 12%) and a significant decrease in
      HR, whereas midazolam was associated with an increase in LF/HF ratio (2.3 +/- 1.1
      versus 3.7 +/- 1.8) with no change in HR. These results indicated a dominant
      parasympathetic effect of propofol and a dominant sympathetic effect of midazolam
      in both periods. These results should be considered during conscious sedation,
      especially in patients at risk of cardiovascular complications.

PMID- 15976214
TI  - The effect of music on preoperative sedation and the bispectral index.
AB  - We assessed the effect of music on the level of sedation and the
      electroencephalograph bispectral index (BIS) during the preoperative period.
      Fifty-four ASA physical status I-II patients, scheduled for elective septo
      rhinoplastic surgery, were included in the study. Subjects were assigned to
      receive either music (music group; n = 28) or no music (control group; n = 26)
      during the preoperative period. Sedative premedication was provided with
      midazolam 0.08 mg/kg IM. Observer's Assessment of Alertness/Sedation Scales
      (OAAS) scores and BIS values were recorded at specific time intervals. In the
      control group, there were more patients with an OAAS score of 1 than in the music
      group at 30 min after midazolam injection. In addition, there were more patients
      with an OAAS score of 2 in the control group than in the music group at 30-50
      min. However, there were significantly more patients with an OAAS score of 3 in
      the music group than in the control group at 20-50 min. BIS values of the music
      group were also smaller than the control group at 30 and 40 min. BIS values were
      significantly decreased from baseline values at 10-50 min in the music group,
      whereas BIS values decreased at 30-50 min in the control group. In conclusion,
      listening to music during midazolam premedication is associated with an increase
      in sedation level in the preoperative period as reflected by a lower BIS value.

PMID- 15976215
TI  - The nerve root entry zone is highly vulnerable to intrathecal tetracaine in
      rabbits.
AB  - It has been speculated that the nerve root entry zone in the spinal cord, known
      as the Obersteiner-Redlich zone, may be more sensitive to large concentrations of
      local anesthetics administered intrathecally. However, there has been no
      morphological evidence for this. In the present study, we examined morphological
      changes of nerve fibers at the nerve root entry zone after administration of
      intrathecal tetracaine in rabbits. Rabbits were assigned to 4 groups (n = 6 in
      each) and received intrathecal 0.3 mL saline (control), or 1%, 2%, or 4%
      tetracaine. Neurological and histopathological assessments were performed 1 wk
      after the administration. Tetracaine 1% selectively injured the myelin sheaths
      made by oligodendrocytes at the nerve root entry zones of both ventral and dorsal
      roots, although neurological dysfunction could not be detected. With tetracaine
      2% and 4%, histopathological damage extended to the dorsal funiculus, distal part
      of roots, and cauda equina and neurological dysfunction became apparent. These
      results demonstrate that the myelin sheaths made by oligodendrocytes at the nerve
      root entry zone are highly vulnerable to large concentrations of tetracaine given
      intrathecally.

PMID- 15976216
TI  - The effect of sildenafil on pulmonary embolism-induced oxidative stress and
      pulmonary hypertension.
AB  - Acute pulmonary embolism (APE) is a major cause of pulmonary hypertension and
      death. We examined the effects of sildenafil on the hemodynamic changes caused by
      APE in anesthetized dogs. Sham-operated dogs (n = 3) received only saline. APE
      was induced by stepwise IV injections of 300 mum microspheres in amounts adjusted
      to increase mean pulmonary artery pressures by 20 mm Hg. Hemodynamic evaluation
      was performed at baseline, after APE was induced, and then after sildenafil 0.25
      mg/kg (n = 8), or sildenafil 1 mg/kg + 0.3 mg . kg(-1) . h(-1) (n = 8) or saline
      (n = 9) infusions were started. Similar experiments were conducted to examine the
      effects of sildenafil in rat isolated perfused lung preparation. Plasma
      thiobarbituric acid reactive species were also determined in both studies to
      measure oxidative stress. Both doses of sildenafil reduced mean pulmonary artery
      pressures in dogs by approximately 8 to 16 mm Hg (both P < 0.05) and attenuated
      the increase in oxidative stress after APE. Mean arterial blood pressure remained
      unaltered after both doses of sildenafil. Sildenafil produced similar effects
      after APE in rat isolated perfused lung preparation. These findings indicate that
      IV sildenafil can selectively attenuate the increases in mean pulmonary artery
      pressures after APE, possibly through antioxidant mechanisms.

PMID- 15976217
TI  - Antibacterial activity of clonidine and neostigmine in vitro.
AB  - We conducted an in vitro study to investigate the antibacterial activity of
      clonidine and neostigmine on common microorganisms encountered during infectious
      complications after regional anesthesia. Standardized suspensions of
      Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli were
      incubated during 1, 3, 6, and 24 h at 37 degrees C with concentrations of 37.5,
      75, and 150 microg/mL of clonidine and 125, 250, and 500 microg/mL of
      neostigmine. After 24 h incubation at 37 degrees C, the colony counts were
      compared by two-way analysis of variance. The mean colony counts for S. aureus
      decreased significantly from control as the exposure to clonidine increased (P <
      0.05), with a approximately 100% kill at 6 h for the largest concentration (150
      microg/mL) and at 24 h for the intermediate concentration (75 microg/mL). Similar
      results were observed for S. epidermidis, with a approximately 100% kill at 6 h
      for the largest concentrations (75 and 150 microg/mL). No bactericidal activity
      of clonidine was observed for E. coli and no bactericidal activity of neostigmine
      was observed for any of the tested strains. In the conditions of this experiment,
      clonidine, but not neostigmine, exhibited a concentration-dependent and time
      dependent bactericidal activity in vitro on the microorganisms most frequently
      encountered in infectious complications after regional anesthesia.

PMID- 15976218
TI  - The effect-site concentration of remifentanil blunting cardiovascular responses
      to tracheal intubation and skin incision during bispectral index-guided propofol
      anesthesia.
AB  - We sought to determine the effect-site concentration of remifentanil blunting
      sympathetic responses to tracheal intubation and skin incision during bispectral
      index (BIS)-guided propofol anesthesia. Forty-one ASA physical status I-II
      patients, aged 20-65 yr and undergoing major abdominal surgery, were randomly
      assigned to one of two groups: tracheal intubation (group TI, n = 20) or skin
      incision (group SI, n = 21). All patients received a target-controlled infusion
      of propofol of 4 microg/mL, which was then adjusted to maintain a BIS value
      ranging between 40 and 50. The effect-site concentration of remifentanil blocking
      the sympathetic responses to tracheal intubation and skin incision in 50% of
      cases (Ce50) was determined using an up-and-down sequential allocation method.
      The mean (95% confidence interval [CI]) Ce50 of remifentanil was 5.0 ng/mL for TI
      (95% CI, 4.7-5.4 ng/mL) and 2.1 ng/mL for SI (95% CI, 1.4-2.8 ng/mL). This study
      shows that effect-site concentrations of remifentanil of 5 ng/mL and 2 ng/mL are
      effective in blunting sympathetic responses to tracheal intubation and skin
      incision in 50% of patients when combined with a BIS-guided target controlled
      infusion of propofol.

PMID- 15976219
TI  - R (+) etomidate and the photoactivable R (+) azietomidate have comparable
      anesthetic activity in wild-type mice and comparably decreased activity in mice
      with a N265M point mutation in the gamma-aminobutyric acid receptor beta3
      subunit.
AB  - A photoactivable diazirine derivative of etomidate, azietomidate, shares many
      actions of etomidate, including a capacity to abolish the righting reflexes in
      tadpoles and enhance gamma-aminobutyric acid (GABA)-induced currents.
      Azietomidate's usefulness in studies of mechanisms of anesthesia depends on the
      assumption that it shares a site of action with etomidate. Mice bearing an N265M
      beta3 subunit point mutation in GABA(A) receptors have a markedly decreased
      sensitivity to loss of righting reflexes induced by etomidate over a range of
      doses. Accordingly, in the present study we measured the time to recovery of
      righting reflexes of wild type and mutant mice as a function of dose given as an
      IV bolus. Analysis of the data for azietomidate yielded mean times to recovery of
      righting reflexes at a dose of 7.5 mg/kg of 10.0 +/- 0.9 min and 3.0 +/- 1.6 min
      for wild type and mutant mice, respectively (mean +/- sd). A similar analysis for
      etomidate yielded mean times to recovery of righting reflexes at a dose of 7.5
      mg/kg of 12.0 +/- 1.3 min and 4.0 +/- 0.7 min for wild type and mutant mice
      respectively. Thus, at this dose a single mutation, N265M on the beta3 subunit of
      the GABA(A) receptor, approximately halved the time to recovery of righting
      reflexes for both etomidate and azietomidate (by 7.6 +/- 1.5 min and 7.2 +/- 1.8
      min, respectively), emphasizing the contribution of this residue as a determinant
      of a behavioral response of azietomidate in mice.

PMID- 15976220
TI  - The effects of isoflurane on airway smooth muscle crossbridge kinetics in Fisher
      and Lewis rats.
AB  - Our aim was to determine how isoflurane modified crossbridge (CB) number and
      kinetics in airway smooth muscle (ASM) and to compare its effects in Fisher and
      Lewis rats, two strains with differences in airway responsiveness. The effects of
      isoflurane (2 MAC) on isotonic and isometric contractility in tracheal ASM strips
      were investigated after methacholine (10(-6) M)-induced contraction. CB mechanics
      and kinetics were analyzed using the formalism of Huxley's equations adapted to
      ASM. After isoflurane, maximum velocity did not differ from baseline in Lewis
      rats, whereas it was significantly less than baseline in Fisher rats (
      approximately 25%), the most reactive strain. Isoflurane totally reversed
      methacholine-induced increase in active CB number in Lewis rats (2.4 +/- 0.5
      versus 1.8 +/- 0.4 10(9)/mm(2) after methacholine and isoflurane, respectively)
      whereas reversal was only partial in Fisher rats (2.7 +/- 0.4 versus 2.1 +/- 0.3
      10(9)/mm(2) after methacholine and isoflurane, respectively). Isoflurane induced
      a 40% increase in attachment step duration in both strains and an almost twofold
      increase in the CB cycle duration compared with baseline in Lewis rats. The
      isoflurane-induced increase in detachment step duration was less in Lewis than in
      Fisher rats (P < 0.05). We concluded that isoflurane modulated CB number and CB
      cycling rates of isolated rat ASM differently depending on the level of airway
      responsiveness.

PMID- 15976221
TI  - The effect of three inhaled anesthetics in mice harboring mutations in the GluR6
      (kainate) receptor gene.
AB  - Combinations of GluR5-GluR7, KA1, and KA2 subunits form kainate receptors, a
      subtype of excitatory ionotropic glutamate receptors. Isoflurane enhances the
      action of kainate receptors comprising GluR6 subunits expressed in oocytes. To
      test whether alterations of the GluR6 subunit gene affect the actions of inhaled
      anesthetics in vivo, we measured the minimum alveolar concentration of
      desflurane, isoflurane, and halothane in mice lacking the kainate receptor
      subunit GluR6 (GluR6 knockout mice) and mice with a dominant negative
      glutamine/arginine (Q/R) editing mutation in membrane domain 2 of the GluR6
      receptor (GluR6 editing mutants), which increases the calcium permeability of
      kainate receptors containing GluR6Q. We also measured the capacity of isoflurane
      to interfere with Pavlovian fear conditioning to a tone and to context. Absence
      of the GluR6 subunit did not change the minimum alveolar concentration of
      isoflurane, desflurane, or halothane. Possibly, kainate receptors assembled from
      the remaining kainate receptor subunits compensate for the absent subunits and
      thereby produce a normal minimum alveolar concentration. A Q/R mutation that
      dominantly affects kainate receptors containing the GluR6 subunit in mice
      increased isoflurane minimum alveolar concentration (by 12%; P < 0.01), decreased
      desflurane minimum alveolar concentration (by 18%; P < 0.001), and did not change
      halothane minimum alveolar concentration (P = 0.25). These data may indicate that
      kainate receptors containing GluR6Q subunits differently modulate, directly or
      indirectly, the mechanism by which inhaled anesthetics cause immobility. The
      mutations of GluR6 that were studied did not affect the capacity of isoflurane to
      interfere with fear conditioning.

PMID- 15976222
TI  - Severe anaphylactic shock with methylene blue instillation.
AB  - We report a documented severe immunoglobulin E-mediated hypersensitivity reaction
      associated with use of 1% methylene blue for detection of tubal permeability
      occurring during general anesthesia. Clinical symptoms, biological assessment
      results, and cutaneous test positivity confirmed an anaphylactic reaction to
      methylene blue. This case report confirms the need for systematic allergological
      investigation of all drugs and substances administered during the perioperative
      period in the event of a hypersensitivity reaction occurring during anesthesia.
      Anesthesiologists should be aware of the possibility of hypersensitivity
      reactions involving any drug or substance used during surgery.

PMID- 15976223
TI  - The effect of a bellows leak in an Ohmeda 7810 ventilator on room contamination,
      inspired oxygen, airway pressure, and tidal volume.
AB  - We investigated the effect of a small bellows leak (bellows full at end
      expiration) on inspired oxygen fraction (Fio(2)), exhaled tidal volume (Vt),
      airway pressure, and room contamination in an oxygen-driven anesthesia ventilator
      (Ohmeda 7810, Madison, WI). CO(2) concentration at the ventilator exhalation
      valve, Fio(2), Vt, and airway pressure were measured (n = 3) while ventilating a
      CO(2)-producing test lung at 8 breaths/min and an inspiratory/expiratory ratio of
      1:2, with and without a bellows leak (4-mm-long tear). Set Vt was 400, 600, 800,
      and 1000 mL. Fresh gas flow (FGF) was 0.3 L/min O(2) and (a) 5.0 L/min air, (b)
      2.0 L/min air, and (c) 0.2 L/min nitrogen. There was no clinical difference in
      Fio(2), Vt, PIP (peak inspiratory pressure) and PEEP (positive end-expiratory
      pressure), with and without a 4-mm bellows tear, at all FGFs and Vt settings.
      CO(2) at the ventilator exhalation valve was always nonzero with a bellows leak,
      indicating that CO(2)-laden circuit gas was contaminating the drive gas via the
      bellows leak. A 4-mm bellows tear in an Ohmeda 7810 ventilator allows anesthetic
      gases to contaminate ambient air but does not cause clinically significant
      changes in Fio(2), exhaled Vt, PIP, or PEEP.

PMID- 15976224
TI  - An improved procedure for catheterization of the thoracic spinal subarachnoid
      space in the rat.
AB  - Catheterization of the subarachnoid space provides a convenient means to deliver
      drugs to, or collect cerebrospinal fluid from, the spinal cord in animal
      experiments, and has been instrumental to our understanding of spinal mechanisms
      that underlie anesthesia, analgesia, or cardiovascular regulation. Experience
      gained over the years has revealed several shortcomings of this technique. We
      report a procedure that encompasses the benefits of direct subarachnoid
      catheterization of the rat thoracic spinal cord but circumvents the known
      shortcomings. An intrathecal catheter was fabricated with a small silicon bead at
      one end of a PE-10 catheter, which was cannulated with a 4/0 suture that served
      as a guide. Using the L-shape hook of the suture guide as an anchorage, the
      catheter was advanced into the subarachnoid space until the silicon bead was
      lodged on a drilled hole (2 x 2 mm) over the lamina proper on the T13 vertebrae.
      With less surgical trauma, greater precision of placement and firmer anchorage of
      the catheter, less leakage of cerebrospinal fluid, and minimal mortality or
      morbidity, our modified procedure for catheterization of the thoracic spinal
      subarachnoid space in the rat compared favorably to previously reported methods.

PMID- 15976225
TI  - Advanced patient monitoring displays: tools for continuous informing.
AB  - We reviewed the use of advanced display technologies for monitoring in
      anesthesia. Researchers are investigating displays that integrate information and
      that, in some cases, also deliver the results continuously to the
      anesthesiologist. Integrated visual displays reveal higher-order properties of
      patient state and speed in responding to events, but their benefits under an
      intensely timeshared load is unknown. Head-mounted displays seem to shorten the
      time to respond to changes, but their impact on peripheral awareness and
      attention is unknown. Continuous auditory displays extending pulse oximetry seem
      to shorten response times and improve the ability to timeshare other tasks, but
      their integration into the already noisy operative environment still needs to be
      tested. We reviewed the advantages and disadvantages of the three approaches,
      drawing on findings from other fields, such as aviation, to suggest outcomes
      where there are still no results for the anesthesia context. Proving that
      advanced patient monitoring displays improve patient outcomes is difficult, and a
      more realistic goal is probably to prove that such displays lead to better
      situational awareness, earlier responding, and less workload, all of which keep
      anesthesia practice away from the outer boundaries of safe operation.

PMID- 15976226
TI  - Emergence from propofol anesthesia in a nonagenarian at a Bispectral Index of 52.
AB  - In this case report, we describe a nonagenarian patient who could respond
      completely to verbal commands at a Bispectral Index (BIS) value of 52 after
      epidural lidocaine and IV propofol anesthesia. Measured blood lidocaine and
      propofol concentrations were 0.69 microg/mL and 0.74 microg/mL, respectively.
      Intraoperative awareness even in the recommended BIS range of 40-60 remains
      possible.

PMID- 15976227
TI  - Occipital nerve electrical stimulation via the midline approach and subcutaneous
      surgical leads for treatment of severe occipital neuralgia: a pilot study.
AB  - Persistent occipital neuralgia can produce severe headaches that may not be
      controllable by conservative or surgical approaches. We describe a case series of
      6 patients who had chronic headaches over an average of 4.9 yr who underwent
      occipital nerve electrical stimulation lead implantation using a modified midline
      approach. The patients had received conservative and surgical therapies in the
      past including oral antidepressants, membrane stabilizers, opioids, occipital
      nerve blocks, and radiofrequency ablations. Significant decreases in pain visual
      analog scale (VAS) scores and drastic improvement in functional capacity were
      observed during the occipital stimulation trial and during the 3-mo follow-up
      after implantation. The mean VAS score changed from 8.66 +/- 1.0 to 2.5 +/- 1.3
      whereas pain disability index improved from 49.8 +/- 15.9 to 14.0 +/- 7.4. Our
      midline approach has several advantages compared with the submastoid approach
      used elsewhere. There is only one small midline incision over the upper neck and
      the strain on the lead extension occurs only with flexion and is minimal with
      lateral flexion and rotation, which contributes to overall stability of this
      system.

PMID- 15976228
TI  - The effect of antinociceptive drugs tested at different times after nerve injury
      in rats.
AB  - Given the evolving nature of anatomical and functional changes in the nervous
      system that are involved in the development of neuropathic pain, it is possible
      that the differing time course after injury underlies the inconsistent efficacy
      of drugs in neuropathic pain patients. In the current study, we evaluated the
      behavioral effects of two standard drugs used clinically for neuropathic pain,
      the anticonvulsant gabapentin and antidepressant imipramine, in rats at different
      times after peripheral nerve injury. Rats that underwent the spared nerve injury
      procedure responded to an innocuous mechanical stimulus (von Frey filament) 2, 4,
      and 8 wk after injury. Gabapentin dose-dependently suppressed mechanical
      sensitivity at all time points tested but the potency of gabapentin was three
      fold less 4 wk postinjury (135 mg/kg) compared with 2 and 8 wk postinjury (41 and
      44 mg/kg, respectively). In contrast, imipramine lacked significant efficacy at 2
      and 8 wk postinjury but slightly attenuated mechanical hypersensitivity at 4 wk
      postinjury. The results show that drug effects may change over time in the
      neuropathic state, which should be an important consideration in the evaluation
      of drugs in preclinical animal pain models and has implications for temporal
      approaches to therapy in the clinic.

PMID- 15976229
TI  - The effects of the tramadol metabolite O-desmethyl tramadol on muscarinic
      receptor-induced responses in Xenopus oocytes expressing cloned M1 or M3
      receptors.
AB  - O-desmethyl tramadol is one of the main metabolites of tramadol. It has been
      widely used clinically and has analgesic activity. Muscarinic receptors are
      involved in neuronal functions in the brain and autonomic nervous system, and
      much attention has been paid to these receptors as targets for analgesic drugs in
      the central nervous system. We have reported that tramadol inhibits the function
      of type-1 muscarinic (M(1)) receptors and type-3 muscarinic (M(3)) receptors,
      suggesting that muscarinic receptors are sites of action of tramadol. However,
      the effects of O-desmethyl tramadol on muscarinic receptor functions have not
      been studied in detail. In this study, we investigated the effects of O-desmethyl
      tramadol on M(1) and M(3) receptors, using the Xenopus oocyte expression system.
      O-desmethyl tramadol (0.1-100 microM) inhibited acetylcholine (ACh)-induced
      currents in oocytes expressing the M(1) receptors (half-maximal inhibitory
      concentration [IC(50)] = 2 +/- 0.6 microM), whereas it did not suppress ACh
      induced currents in oocytes expressing the M(3) receptor. Although GF109203X, a
      protein kinase C inhibitor, increased the ACh-induced current, it had little
      effect on the inhibition of ACh-induced currents by O-desmethyl tramadol in
      oocytes expressing M(1) receptors. The inhibitory effect of O-desmethyl tramadol
      on M(1) receptor was overcome when the concentration of ACh was increased (K(D)
      with O-desmethyl tramadol = 0.3 microM). O-desmethyl tramadol inhibited the
      specific binding of [(3)H]quinuclidinyl benzilate ([(3)H]QNB) to the oocytes
      expressed M(1) receptors (IC(50) = 10.1 +/- 0.1 microM), whereas it did not
      suppress the specific binding of [(3)H]QNB to the oocytes expressed M(3)
      receptors. Based on these results, O-desmethyl tramadol inhibits functions of
      M(1) receptors but has little effect on those of M(3) receptors. This study
      demonstrates the molecular action of O-desmethyl tramadol on the receptors and
      may help to explain its neural function.

PMID- 15976230
TI  - Reduction of anesthesia process times after the introduction of an internal
      transfer pricing system for anesthesia services.
AB  - To improve operating room workflow, an internal transfer pricing system (ITPS)
      for anesthesia services was introduced in our hospital in 2001. The basic
      principle of the ITPS is that the department of anesthesia receives reimbursement
      only for the surgically controlled time, not for anesthesia-controlled time
      (ACT). A reduction in anesthesia process times is therefore beneficial for the
      anesthesia department. In this study, we analyzed the ACT (with its parts:
      preparation before induction, induction, extubation, and recovery room transfer)
      for 3 yr before and 3 yr after the introduction of the ITPS in 55,776 cases.
      Furthermore, the anesthesia cases were subsegmented into 10 different anesthesia
      techniques, and the process times were studied. The average total ACT was reduced
      from 40.4 +/- 23.5 min in 1998 to 34.3 +/- 21.7 min in 2003. The main effect came
      from reductions in anesthesia preparation time and recovery room transfer time,
      whereas induction and extubation time changed little. A significant reduction in
      average ACT was seen in 7 of 10 analyzed anesthesia techniques, ranging from 4 to
      18 min. We conclude that transfer pricing of anesthesia services based on the
      surgically controlled time can be a successful approach to reduce anesthesia
      process times.

PMID- 15976231
TI  - The impact of productivity-based incentives on faculty salary-based compensation.
AB  - In industry and academic anesthesia departments, incentives and bonus payments
      based on productivity are accounting for an increasing proportion of a total
      compensation. When incentives are primarily based on clinical productivity, the
      impact on the distribution of total compensation to the faculty is not known. We
      compared a pure salary-based compensation methodology based entirely on academic
      rank to salary plus incentives and/or clinical productivity compensation (i.e.,
      billable hours). The change in compensation methodology resulted in two major
      findings. First, the productivity-based compensation resulted in a large increase
      in the variability of total compensation among faculty, especially at the
      Assistant Professor rank. Second, the mean difference in total compensation
      between Assistant and Full Professors decreased. The authors conclude that this
      particular incentive plan, primarily directed toward clinical productivity,
      dramatically changed the distribution of total compensation in favor of junior
      faculty. Although not analytically investigated, the potential impact of these
      changes on faculty morale and distribution of faculty activities is discussed.

PMID- 15976232
TI  - Over-the-head cardiopulmonary resuscitation improves efficacy in basic life
      support performed by professional medical personnel with a single rescuer: a
      simulation study.
AB  - Two-rescuer cardiopulmonary resuscitation (CPR) is considered the best method for
      professional basic life support (BLS). However, in many prehospital cardiac
      arrest situations, one rescuer has to begin CPR alone while the other performs
      additional tasks. In theory, over-the-head CPR is a suitable alternative in this
      situation, with the added benefit of allowing the single rescuer to use a self
      inflating bag for ventilation. In this trial, we compared standard single-rescuer
      CPR with over-the-head CPR in manikins. We planned this study using a crossover
      study design where each participant administered both CPR techniques in a
      randomized order. Ventilation and chest compression data were collected with
      analysis software during a 2-min CPR test for each technique. Sixty-seven
      emergency medical technician students participated in this trial. Over-the-head
      CPR allowed for superior ventilation compared to standard CPR (number of correct
      ventilations: 330 of 760 versus 279 of 779; P = 0.002). The quality of delivered
      chest compressions did not differ between the two groups (correct chest
      compressions: 4293 of 6304 versus 4313 of 6395; P = 0.44). In conclusion, our
      study has shown that over-the-head CPR may be an effective alternative BLS
      technique when a single professional rescuer has to perform CPR, likely offering
      superior ventilation and comparable chest compression quality compared with
      standard BLS.

PMID- 15976233
TI  - Estimation of functional residual capacity at the bedside using standard
      monitoring equipment: a modified nitrogen washout/washin technique requiring a
      small change of the inspired oxygen fraction.
AB  - We developed a modified nitrogen washin/washout technique based on standard
      monitors using inspiratory and end-tidal gas concentration values for functional
      residual capacity (FRC) measurements in patients with acute respiratory failure
      (ARF). For validation we used an oxygen-consuming lung model ventilated with an
      inspiratory oxygen fraction (Fio(2)) between 0.3 and 1.0. The respiratory
      quotient of the lung model was varied between 0.7 and 1.0. Measurements were
      performed changing Fio(2) with fractions of 0.1, 0.2, and 0.3. In 28 patients
      with ARF, duplicate measurements were performed. In the lung model, an Fio(2)
      change of 0.1 resulted in a value of 103 +/- 5% of the reference FRC value of the
      lung model, and the precision was equally good up to an Fio(2) of 1.0 with a
      value of 103 +/- 7%. In the patients, duplicate measurements showed a bias of -5
      mL with a 95% confidence interval [-38; 29 mL ]. A comparison of a change in
      Fio(2) of 0.1 with 0.3 showed a bias of -9 mL and limits of agreement of [-365;
      347 mL]. This study shows good precision of FRC measurements with standard
      monitors using a change in Fio(2) of only 0.1. Measurements can be performed with
      equal precision up to an Fio(2) of 1.0.

PMID- 15976234
TI  - Serine antiproteinase administration preserves innate superoxide dismutase levels
      after acid aspiration and hyperoxia but does not decrease lung injury.
AB  - Acute lung injury after acid aspiration and increased ambient oxygen result in
      significant oxidative damage to the lungs. Lung antioxidant levels are also
      reduced. Because levels of serine proteinases in the airspaces are also
      dramatically increased, we hypothesized that these enzymes play a role in
      degrading lung antioxidants. Rats were treated with a serine proteinase
      inhibitor, aprotinin, before pulmonary aspiration of acid in the presence of
      increased ambient oxygen (hyperoxia). Lung Cu/Zn and Mn superoxide dismutase
      (SOD) activity (by colorimetric assay) and Cu/Zn SOD immune reactive protein
      (enzyme-linked immunosorbent assay) were assayed. The effects of antiproteinase
      treatment on acute lung injury were also assessed. Total SOD, Cu/Zn SOD, and
      Cu/Zn SOD antigenic protein levels were decreased in animals after acid
      aspiration and hyperoxia. However, Mn SOD activity was unchanged. The decrease in
      Cu/Zn SOD was attenuated in animals, where serine proteinase activity was
      inhibited. However, antiproteinase treatment did not decrease acute pulmonary
      injury, as assessed by leakage of radiolabeled albumin into the lung
      (permeability index), arterial blood gases, and markers of acute inflammation
      (pulmonary myeloperoxidase activity, a surrogate neutrophilic marker, and
      inflammatory cytokine profiles). We conclude that production of serine
      proteinases play a major role in degrading Cu/Zn SOD, thereby decreasing
      pulmonary antioxidant capacity. However, the role this plays in the pathogenesis
      of the acute lung injury is not clear.

PMID- 15976235
TI  - The comparative evaluation of gabapentin and carbamazepine for pain management in
      Guillain-Barre syndrome patients in the intensive care unit.
AB  - We evaluated the effects of gabapentin and carbamazepine for pain relief in 36
      Guillain-Barre syndrome patients. Patients were randomly assigned to receive
      gabapentin 300 mg, carbamazepine 100 mg, or matching placebo 3 times a day for 7
      days. Fentanyl 2 microg/kg was used as a supplementary analgesic on patient
      demand. The pain score was recorded by using a numeric pain rating scale of 0-10,
      and sedation was recorded with a Ramsay sedation scale of 1-6 before medications
      were given and then at 6-h intervals throughout the study period. Total daily
      fentanyl consumption was recorded each day for each patient. The results of the
      study demonstrated that patients in the gabapentin group had significantly lower
      (P < 0.05) median numeric pain rating scale scores (3.5, 2.5, 2.0, 2.0, 2.0, 2.0,
      and 2.0) compared with patients in the placebo group (6.0, 6.0, 6.0, 6.0, 6.0,
      6.0, and 6.0) and the carbamazepine group (6.0, 6.0, 5.0, 4.0, 4.0, 3.5, and
      3.0). There was no significant difference in fentanyl consumption between the
      gabapentin and carbamazepine groups on Day 1 (340.1 +/- 34.3 microg and 347.5 +/-
      38.0 microg, respectively), but consumption was significantly less in these 2
      groups compared with the placebo group (590.4 +/- 35.0 microg) (P < 0.05). For
      the rest of the study period, there was a significant difference in fentanyl
      consumption among all treatment groups, and it was minimal in the gabapentin
      group (P < 0.05). We conclude that gabapentin is more effective than
      carbamazepine for decreasing pain and fentanyl consumption.

PMID- 15976236
TI  - Catecholamines' enhancement of inducible nitric oxide synthase-induced nitric
      oxide biosynthesis involves CAT-1 and CAT-2A.
AB  - Catecholamines enhance inducible nitric oxide synthase (iNOS) expression that
      results in nitric oxide (NO) overproduction in lipopolysaccharide (LPS)
      stimulated macrophages. L-arginine transport mediated by cationic amino acid
      transporters (including CAT-1, CAT-2, CAT-2A, and CAT-2B) is crucial in
      regulating iNOS activity. We sought to assess the effects of catecholamines on L
      arginine transport and CAT isozyme expression in stimulated macrophages.
      Confluent RAW264.7 cells were cultured with LPS with or without catecholamines
      (epinephrine or norepinephrine, 5 x 10(-6) M) for 18 h. NO production, L-arginine
      transport, and enzyme expression were determined. Our data revealed that LPS co
      induced iNOS, CAT-2, and CAT-2B expression, whereas CAT-1 and CAT-2A expression
      remained unaffected. Significant increases in NO production and L-arginine
      transport (approximately eight-fold and three-fold increases, respectively) were
      found in activated macrophages. Catecholamines significantly enhanced NO
      production and L-arginine transport (approximately 30% and 20% increases,
      respectively) in activated macrophages. Catecholamines also enhanced the
      expression of iNOS, CAT-1, and CAT-2A but not CAT-2 or CAT-2B in LPS-stimulated
      macrophages. Furthermore, the enhancement effects of catecholamines were
      inhibited by either dexamethasone or propranolol. We provide the first evidence
      to indicate that L-arginine transport in activated macrophages could be enhanced
      by catecholamines. Furthermore, this catecholamine-enhanced L-arginine transport
      might involve CAT-1 and CAT-2A but not CAT-2 or CAT-2B.

PMID- 15976237
TI  - Aortic dissection mimicking subarachnoidal hemorrhage.
AB  - In this report we describe a comatose patient with proximal aortic dissection who
      presented with the signs of subarachnoidal hemorrhage. Shortly before losing
      consciousness, the patient complained of an excruciating headache. Upon initial
      examination, neck stiffness and opisthotonos were present. The cardiovascular
      examination, chest radiograph, and cerebral computed tomography were normal.
      Eight hours later, the aortic dissection was verified by a thoracic computed
      tomography. This case shows that aortic dissection, which causes severe pain and
      possibly transient malperfusion of the carotid arteries, may present with the
      misleading signs of subarachnoidal hemorrhage but without classical symptoms of
      aortic syndromes.

PMID- 15976239
TI  - Spinal cord blood flow change by intravenous midazolam during isoflurane
      anesthesia.
AB  - We investigated the effects of IV midazolam on spinal cord blood flow in 32 cats
      anesthetized with isoflurane. Cats underwent laminectomy, and the lumbar spinal
      cord was exposed. A platinum electrode was inserted stereotaxically into the
      spinal cord to a depth of 1 mm-2 mm lateral to midline at L2. Arterial blood
      pressure, heart rate, and spinal cord blood flow (using the hydrogen clearance
      method) were measured before and at 5, 15, 30, 60, 90, and 120 min after an IV
      bolus of midazolam (0, 1, 2, or 4 mg/kg in saline 5 mL; n = 8 cats per dose).
      Arterial blood pressure was not affected by 0 or 1 mg/kg of midazolam but was
      decreased for 30 min by 2 or 4 mg/kg of midazolam. Heart rate did not change.
      Spinal cord blood flow was increased for 90 min by midazolam 1 mg/kg and for 15
      min by midazolam 2 mg/kg but was not changed by midazolam 4 mg/kg. In conclusion,
      1 mg/kg of midazolam increased feline spinal cord blood flow without changing
      arterial blood pressure. In contrast, a larger dose of midazolam (4 mg/kg) did
      not change spinal cord blood flow but substantially decreased arterial blood
      pressure during isoflurane anesthesia.

PMID- 15976238
TI  - Bilateral bispectral index monitoring during suppression of unilateral
      hemispheric function.
AB  - Bispectral Index (BIS) has been used to monitor level of "sedation" based on the
      electroencephalogram (EEG). Patients evaluated for surgery to control a seizure
      disorder undergo Wada testing, during which one hemisphere is rendered
      functionally inactive after injecting a short-acting barbiturate. We surmised
      that the BIS values would reflect these functional changes. Eight epileptic
      patients were enrolled. A full array of 21 EEG electrodes and 2 BIS XP (Quatro)
      strips over each frontal region of the scalp were applied. The EEG was
      continuously recorded. BIS values from each hemisphere were recorded every
      minute. Angiography was performed by advancing a catheter into each internal
      carotid artery. Amobarbital or methohexital was injected until the patient
      developed a hemiparesis. The EEG confirmed a significant lateralized cortical
      effect of the barbiturate. Repeated measures analysis of variance was used to
      analyze the differences between the BIS values from monitor electrode strips
      placed on the left (left BIS) and the right (right BIS) sides of the head as well
      as the differences in the left and right BIS values before and after each
      injection of the barbiturate. Injection of barbiturate into either the left or
      right internal carotid artery produced a significant change on the 21-electrode
      EEG. However, there was no difference between left BIS to right BIS values (P =
      0.84). With repeated injections of barbiturates, some patients became sedated. At
      these times, both left BIS and right BIS values decreased together before and
      after injection of barbiturate. The BIS monitor was unable to distinguish
      significant hemispheric EEG and clinical functional changes except when the
      patient became sedated.

PMID- 15976240
TI  - Errors and omissions in anesthesia: a pilot study using a pilot's checklist.
AB  - There are recent concerns that anesthesiologists are becoming less skilled in
      providing general anesthesia for Cesarean delivery. We considered whether a
      verbal checklist would help in the preparation for this event. We created a list
      of items to be checked when preparing to administer general anesthesia for a
      Cesarean delivery using expert opinion. This list was loaded onto an electronic
      checklist system with voice prompts and tested on 20 anesthesiologists using a
      high-fidelity anesthesia simulator. Participants omitted to check a median of 13
      (range, 7-23) of 40 items. Common omissions included not checking that the
      difficult intubation trolley was available and not optimizing the patient's head
      position. Most (95%) participants felt that the checklist was useful and 80%
      would like to use it for practicing simulated scenarios; 60% preferred a written
      checklist and 40% preferred the verbal checklist. Important checks may be
      forgotten when preparing to give a general anesthetic for Cesarean delivery, and
      the use of a checklist could improve patient safety.

PMID- 15976241
TI  - Remifentanil for fetal immobilization and maternal sedation during fetoscopic
      surgery: a randomized, double-blind comparison with diazepam.
AB  - Obstetric endoscopy procedures are routinely performed at our institution to
      treat selected complications of monochorionic twin gestation. We perform these
      procedures under combined spinal epidural anesthesia plus maternal sedation. In
      the absence of general anesthesia, fetal immobilization is not achieved. We
      hypothesized that remifentanil would induce adequate maternal sedation and
      provide fetal immobilization, which is equal or superior to that induced by
      diazepam. Fifty-four second trimester pregnant women were included in this
      randomized, double-blind trial. After combined spinal epidural anesthesia,
      maternal sedation was initiated using either incremental doses of diazepam or a
      continuous infusion of remifentanil. Maternal sedation, hemodynamics, side
      effects, and fetal hemodynamics and immobilization were evaluated before, during,
      and for 60 min after surgery. Remifentanil produced adequate maternal sedation
      with mild but clinically irrelevant respiratory depression (respiratory rate 13
      +/- 4 breaths/min and Pco(2) 38.6 +/- 4 mm Hg at 40 min of surgery), whereas
      diazepam resulted in a more pronounced maternal sedation but no respiratory
      depression (respiratory rate 18 +/- 3 breaths/min and Pco(2) 32.7 +/- 3 mm Hg at
      40 min of surgery). Compared with diazepam, fetal immobilization with
      remifentanil occurred faster and was more pronounced, resulting in improved
      surgical conditions; the number of gross body and limb movements was 12 +/- 4
      (diazepam) versus 2 +/- 1 (remifentanil) at 40 min of surgery. Because of this,
      the mean (range) duration of surgery was significantly shorter in the
      remifentanil-treated patients, 60 (54-71) min versus 80 (60-90) min in the
      diazepam group. We conclude that remifentanil produces improved fetal
      immobilization with good maternal sedation and only minimal effects on maternal
      respiration.

PMID- 15976242
TI  - In with the new, out with the old? Comparison of two approaches for psoas
      compartment block.
AB  - We compared the approaches of Winnie and Capdevila for psoas compartment block
      (PCB) performed by a single operator in terms of contralateral spread, lumbar
      plexus blockade, and postoperative analgesic efficacy. Sixty patients underwent
      PCB (0.4 mL/kg levobupivacaine 0.5%) and subsequent spinal anesthesia for primary
      joint arthroplasty (hip or knee) in a prospective, double-blind study. Patients
      were randomly allocated to undergo PCB by using the Capdevila (group C; n = 30)
      or a modified Winnie (group W; n = 30) approach. Contralateral spread and lumbar
      plexus blockade were assessed 15, 30, and 45 min after PCB. Contralateral spread
      (bilateral from T4 to S5) and femoral and lateral cutaneous nerve block were
      evaluated by sensory testing, and obturator motor block was assessed. Bilateral
      anesthesia occurred in 10 patients in group C and 12 patients in group W (P =
      0.8). Blockade of the femoral, lateral cutaneous, and obturator nerves was 90%,
      93%, and 80%, respectively, for group C and 93%, 97%, and 90%, respectively, for
      group W (P > 0.05). No differences were found in PCB procedure time, pain scores,
      24-h morphine consumption, or time to first morphine analgesia.

PMID- 15976243
TI  - Epidural analgesia prevents endotoxin-induced gut mucosal injury in rabbits.
AB  - In the present study, we evaluated the effect of epidural analgesia on the
      alterations of gut barrier function elicited by endotoxin in rabbits. After the
      placement of an epidural catheter, 28 male rabbits were randomized into either
      0.5% lidocaine (group E) or saline (group C) group. The solutions (0.4 mL/kg)
      were epidurally injected, followed by continuous infusion (0.1 mL . kg(-1) . h(
      1)) throughout the study period. Under a continuous infusion of
      lipopolysaccharide (15 microg . kg(-1) . h(-1)), mean arterial blood pressure,
      intramucosal pH, and plasma thrombomodulin concentrations were measured. At 4 h,
      mean arterial blood pressure was lower (P < 0.05), intramucosal pH was higher (P
      < 0.01), and the progression of hemodilution more profound (P < 0.05) in group E
      versus group C, whereas plasma thrombomodulin levels were increased to a similar
      extent between the groups. With less wet-to-dry weight ratio of ileum,
      histopathological injury scores of gut mucosa were significantly less in group E
      versus group C (P < 0.01). In a separate series of experiments (n = 10 each
      group), mucosal permeability in group E was significantly less compared with
      group C (P < 0.05). Collectively, these studies showed that despite a significant
      decrease of perfusion pressure and arterial oxygen content, epidural analgesia
      minimized endotoxin-induced functional and structural injury of gut mucosa
      possibly through endothelium-independent mechanisms.

PMID- 15976244
TI  - The vertical infraclavicular brachial plexus block: a simulation study using
      magnetic resonance imaging.
AB  - The recommended needle trajectory for the vertical infraclavicular brachial
      plexus block is anteroposterior, caudad to the middle of the clavicle. We studied
      the risk of pneumothorax and subclavian vessel puncture and the precision of this
      method by using magnetic resonance imaging in 20 adult volunteers. The trajectory
      aimed at the lung in six subjects, five of whom were women. However, pleural
      contact could be avoided in all subjects by halting needle advancement after
      contact with the subclavian vessels, plexus, or first rib. The subclavian vein
      was reached by the trajectory in three and the subclavian artery in five
      subjects. The trajectory had a median distance to the plexus (closest aspect) of
      1 mm (range, 0-9 mm) and contacted the nerves in 9 subjects. In conclusion, there
      is a small probability that the needle may reach the pleura when a vertical
      infraclavicular brachial plexus block is performed, particularly in women, and a
      high probability that it will contact the subclavian vein or artery. Although the
      trajectory is close to the plexus, any medial deviation carries the risk of
      pleural or subclavian vessel contact at other depths. Clinical accuracy in
      defining the insertion point is critical.

PMID- 15976245
TI  - The effects of interscalene brachial plexus block on humeral arterial blood flow:
      a Doppler ultrasound study.
AB  - In this study we investigated and quantified the effects of interscalene block
      (ISB) on humeral arterial blood flow (HBF). Eleven patients scheduled for
      shoulder arthroscopic surgery under ISB were prospectively studied. A Doppler
      ultrasound of the humeral artery was performed before, and 30 min after, the ISB.
      The resistance index and the HBF were measured at the level of the midpoint of
      the upper arm. The median (interquartile range) of resistance index decreased
      from 0.98 (0.95-1.00) to 0.81 (0.77-0.91) (P < 0.01). The median HBF increased
      from 32 (18-46) to 88 (59-98) mL/min (P < 0.01). We conclude that ISB enhances
      arterial blood flow and decreases arterial resistance.

PMID- 15976246
TI  - Mandibular nerve blocks for the removal of dentures during trismus caused by
      tetanus.
AB  - We report a case of trismus caused by tetanus in an 80-yr-old woman who developed
      severe and painful masseter spasms during which she violently bit the tip of her
      tongue with her dentures. Bilateral mandibular blocks were performed to remove
      the dentures. The patient fully recovered. We suggest that mandibular blocks are
      a useful tool in the management of oral events during trismus in conscious
      patients.

PMID- 15976247
TI  - The reliability and validity of the upper lip bite test compared with the
      Mallampati classification to predict difficult laryngoscopy: an external
      prospective evaluation.
AB  - Recently, a new bedside screening test to predict the occurrence of a difficult
      laryngoscopy has been developed as a substitute for the Mallampati
      classification. The Upper-Lip-Bite test (ULBT) evaluated the patient's ability to
      reach or completely cover the upper lip with the lower incisors. It is often
      accepted that new predictive tools should undergo an external evaluation before
      the tool is used in clinical practice. Thus, we evaluated this test with respect
      to applicability, interobserver reliability, and discriminating power and
      compared it with the Mallampati-score (using Samsoon and Young's modification).
      The ULBT could not be applied in 12% of all patients (Mallampati score, <1%).
      However, the interobserver reliability was better for the ULBT (kappa = 0.79
      versus kappa = 0.59). The discriminating power to predict a patient with
      difficult laryngoscopy was evaluated in 1425 consecutive patients. Both tests
      were assessed simultaneously in these patients by two specially trained
      independent observers. After the induction of anesthesia, the laryngoscopic view
      was assessed by the attending anesthesiologist using the classification of
      Cormack and Lehane. A grade I or II was called easy laryngoscopy and grade III
      and IV difficult laryngoscopy. The discriminating power for both tests was low
      (0.60 for the ULBT [95% confidence interval, 0.57-0.63] and 0.66 [0.63-0.69]) for
      the Mallampati score), indicating that both tests are poor predictors as single
      screening tests.

PMID- 15976248
TI  - Gargling with sodium azulene sulfonate reduces the postoperative sore throat
      after intubation of the trachea.
AB  - Postoperative sore throat (POST) is a complication that remains to be resolved in
      patients undergoing endotracheal intubation. In this study, we investigated
      whether preoperative gargling with sodium 1,4-dimethyl-7-isopropylazulene-3
      sulfonate monohydrate (sodium azulene sulfonate, Azunol) reduces POST after
      endotracheal intubation. Forty patients scheduled for elective surgery under
      general anesthesia were randomized into Azunol and control groups. In the Azunol
      group, patients gargled with 4 mg Azunol diluted with 100 mL tap water (40
      microg/mL). In the control group, patients gargled with 100 mL of tap water.
      After emergence from general anesthesia, the patients with POST were counted and
      POST was evaluated using a verbal analog pain scale. There were no significant
      differences between the two groups by age, height, body weight, gender
      distribution, or duration of anesthesia and surgery. In the control group, 13
      patients (65%) complained of POST, which remained 24 h later in nine patients
      (45%). In the Azunol group, five patients (25%) also complained of POST, which
      completely disappeared by 24 h later. The incidence of POST and verbal analog
      pain scale scores in the Azunol group decreased significantly compared with the
      control group. We demonstrated that gargling with Azunol effectively attenuated
      POST with no adverse reactions.

PMID- 15976249
TI  - Unusual foreign body airway obstruction after laryngeal mask airway insertion.
AB  - Airway obstruction during general anesthesia is fairly common. Foreign body
      causing obstruction of the laryngeal mask airway is uncommon but can confuse the
      anesthesiologist trying to troubleshoot the cause of inability to ventilate. We
      present a case of complete airway obstruction with a nematode caught in the
      vertical bars of the laryngeal mask airway after its insertion.

PMID- 15976250
TI  - Stylet stuck in the back: an unusual complication of spinal needle.

PMID- 15976252
TI  - Is a desflurane-remifentanil based anesthetic really the best for the wake-up
      test?

PMID- 15976253
TI  - The soft seal laryngeal mask provides good ease of insertion and clinical
      performance.

PMID- 15976255
TI  - Awake and paralyzed: was it really necessary?

PMID- 15976256
TI  - Artifactual increase in the arterial pressure waveform: remember the stopcock.

PMID- 15976258
TI  - Assessment of the optimal cerebral perfusion pressure in head-injured patients.

PMID- 15976260
TI  - Desflurane versus sevoflurane.

PMID- 15976261
TI  - Subarachnoid block in a patient with essential thrombocytemia.

PMID- 15976264
TI  - Comparison of propofol with lidocaine pretreatment versus propofol formulated
      with long- and medium-chain triglycerides or confounding effect of tourniquet.

PMID- 15976265
TI  - Anesthesia for a child with reflex anoxic seizures.

PMID- 15976266
TI  - Ambesh's T-Dagger: a new device for quick bedside percutaneous dilational
      tracheostomy.

PMID- 15976267
TI  - Unanticipated dural tap in caudal anesthesia: a case of intrasacral meningocele.

PMID- 15976268
TI  - Abnormal maturation of the retinal vasculature in type XVIII collagen/endostatin
      deficient mice and changes in retinal glial cells due to lack of collagen types
      XV and XVIII.
AB  - Type XVIII collagen is important in the early phase of retinal vascular
      development and for the regression of the primary vasculature in the vitreous
      body after birth. We show here that the retina in Col18a1-/- mice becomes densely
      vascularized by anomalous anastomoses from the persistent hyaloid vasculature by
      day 10 after birth. In situ hybridizations revealed normal VEGF mRNA expression,
      but the phenotype of collagen XVIII deficient mice closely resembled that of mice
      expressing VEGF120 and VEGF188 isoforms only, suggesting that type XVIII collagen
      may be involved in VEGF function. Type XVIII collagen was found to be
      indispensable for angiogenesis in the eye, as also oxygen-induced
      neovascularization was less intense than normal in the Col18a1-/- mice. We
      observed a marked increase in the amount of retinal astrocytes in the Col18a1-/-
      mice. Whereas the retinal vessels of wild-type mice are covered by astrocytes and
      the regressing, thin hyaloid vessels are devoid of astrocytes, the retinal
      vessels in the Col18a1-/- mice were similarly covered by astrocytes but not the
      persistent hyaloid vessels in the vitreous body. Interestingly, double null mice
      lacking type XVIII collagen and its homologue type XV collagen had the persistent
      hyaloid vessels covered by astrocytes, including the parts located in the
      vitreous body. We thus hypothesize that type XV collagen is a regulator of glial
      cell recruitment around vessels and that type XVIII collagen regulates their
      proliferation.

PMID- 15976269
TI  - Cytokinin oxidase regulates rice grain production.
AB  - Most agriculturally important traits are regulated by genes known as quantitative
      trait loci (QTLs) derived from natural allelic variations. We here show that a
      QTL that increases grain productivity in rice, Gn1a, is a gene for cytokinin
      oxidase/dehydrogenase (OsCKX2), an enzyme that degrades the phytohormone
      cytokinin. Reduced expression of OsCKX2 causes cytokinin accumulation in
      inflorescence meristems and increases the number of reproductive organs,
      resulting in enhanced grain yield. QTL pyramiding to combine loci for grain
      number and plant height in the same genetic background generated lines exhibiting
      both beneficial traits. These results provide a strategy for tailormade crop
      improvement.

PMID- 15976270
TI  - Ice sheet and solid Earth influences on far-field sea-level histories.
AB  - Previous predictions of sea-level change subsequent to the last glacial maximum
      show significant, systematic discrepancies between observations at Tahiti, Huon
      Peninsula, and Sunda Shelf during Lateglacial time (approximately 14,000 to 9000
      calibrated years before the present). We demonstrate that a model of glacial
      isostatic adjustment characterized by both a high-viscosity lower mantle (4 x
      10(22) Pa s) and a large contribution from the Antarctic ice sheet to meltwater
      pulse IA (approximately 15-meters eustatic equivalent) resolves these
      discrepancies. This result supports arguments that an early and rapid Antarctic
      deglaciation contributed to a sequence of climatic events that ended the most
      recent glacial period of the current ice age.

PMID- 15976271
TI  - Permanent El Nino-like conditions during the Pliocene warm period.
AB  - During the warm early Pliocene (approximately 4.5 to 3.0 million years ago), the
      most recent interval with a climate warmer than today, the eastern Pacific
      thermocline was deep and the average west-to-east sea surface temperature
      difference across the equatorial Pacific was only 1.5 +/- 0.9 degrees C, much
      like it is during a modern El Nino event. Thus, the modern strong sea surface
      temperature gradient across the equatorial Pacific is not a stable and permanent
      feature. Sustained El Nino-like conditions, including relatively weak zonal
      atmospheric (Walker) circulation, could be a consequence of, and play an
      important role in determining, global warmth.

PMID- 15976273
TI  - Science and prohibited weapons.

PMID- 15976272
TI  - Antagonistic control of disease resistance protein stability in the plant immune
      system.
AB  - Pathogen recognition by the plant immune system is governed by structurally
      related, polymorphic products of disease resistance (R) genes. RAR1 and/or SGT1b
      mediate the function of many R proteins. RAR1 controls preactivation R protein
      accumulation by an unknown mechanism. We demonstrate that Arabidopsis SGT1b has
      two distinct, genetically separable functions in the plant immune system: SGT1b
      antagonizes RAR1 to negatively regulate R protein accumulation before infection,
      and SGT1b has a RAR1-independent function that regulates programmed cell death
      during infection. The balanced activities of RAR1 and SGT1, in concert with
      cytosolic HSP90, modulate preactivation R protein accumulation and signaling
      competence.

PMID- 15976275
TI  - Condensed matter physics. Tiny whirlpools prove atoms flow freely.

PMID- 15976274
TI  - European Union. Political crisis puts Europe's research ambitions in doubt.

PMID- 15976276
TI  - Infectious diseases. Lapses worry bird flu experts.

PMID- 15976277
TI  - European patents. BRCA2 claim faces new challenge.

PMID- 15976278
TI  - Nuclear science. RHIC gets nod over JLab in worst-case DOE scenario.

PMID- 15976279
TI  - Taiwan. New university president has links to paranormal research.

PMID- 15976280
TI  - Behavior. Bird alarm calls size up predators.

PMID- 15976281
TI  - Marine biology. Microbe may push photosynthesis into deep water.

PMID- 15976282
TI  - Neurology. Autistic brains out of synch?

PMID- 15976283
TI  - Pharmacogenomics. Going from genome to pill.

PMID- 15976284
TI  - Central Asia. Visions of a biotech empire on the Kazakh Steppe.

PMID- 15976285
TI  - Cell biology: The ins and outs of exosomes.

PMID- 15976286
TI  - Problems with co-funding in Canada.

PMID- 15976287
TI  - Issues in biosecurity and biosafety.

PMID- 15976288
TI  - Problems in patenting human genes.

PMID- 15976289
TI  - Comment on "S-nitrosylation of parkin regulates ubiquitination and compromises
      parkin's protective function".

PMID- 15976291
TI  - Voting technology. Election auditing is an end-to-end procedure.

PMID- 15976292
TI  - Biomedicine. The anti-aging sweepstakes: catalase runs for the ROSes.

PMID- 15976293
TI  - Chemistry. Dioxygen surprises.

PMID- 15976294
TI  - Oceans. How does the Antarctic ice sheet affect sea level rise?

PMID- 15976295
TI  - Immunology. Close to the edge: neutralizing the HIV-1 envelope.

PMID- 15976296
TI  - Larger islands house more bacterial taxa.
AB  - The power law that describes the relationship between species richness and area
      size is one of the few generalizations in ecology, but recent studies show that
      this relationship differs for microbes. We demonstrate that the natural bacterial
      communities inhabiting small aquatic islands (treeholes) do indeed follow the
      species-area law. The result requires a re-evaluation of the current
      understanding of how natural microbial communities operate and implies that
      analogous processes structure both microbial communities and communities of
      larger organisms.

PMID- 15976298
TI  - Sound velocities of hot dense iron: Birch's law revisited.
AB  - Sound velocities of hexagonal close-packed iron (hcp-Fe) were measured at
      pressures up to 73 gigapascals and at temperatures up to 1700 kelvin with nuclear
      inelastic x-ray scattering in a laser-heated diamond anvil cell. The
      compressional-wave velocities (VP) and shear-wave velocities (VS) of hcp-Fe
      decreased significantly with increasing temperature under moderately high
      pressures. VP and VS under high pressures and temperatures thus cannot be fitted
      to a linear relation, Birch's law, which has been used to extrapolate measured
      sound velocities to densities of iron in Earth's interior. This result means that
      there are more light elements in Earth's core than have been inferred from linear
      extrapolation at room temperature.

PMID- 15976297
TI  - Tyrosinase reactivity in a model complex: an alternative hydroxylation mechanism.
AB  - The binuclear copper enzyme tyrosinase activates O2 to form a mu-eta2:eta2
      peroxodicopper(II) complex, which oxidizes phenols to catechols. Here, a
      synthetic mu-eta2:eta2-peroxodicopper(II) complex, with an absorption spectrum
      similar to that of the enzymatic active oxidant, is reported to rapidly
      hydroxylate phenolates at -80 degrees C. Upon phenolate addition at extreme
      temperature in solution (-120 degrees C), a reactive intermediate consistent with
      a bis-mu-oxodicopper(III)-phenolate complex, with the O-O bond fully cleaved, is
      observed experimentally. The subsequent hydroxylation step has the hallmarks of
      an electrophilic aromatic substitution mechanism, similar to tyrosinase. Overall,
      the evidence for sequential O-O bond cleavage and C-O bond formation in this
      synthetic complex suggests an alternative intimate mechanism to the concerted or
      late stage O-O bond scission generally accepted for the phenol hydroxylation
      reaction performed by tyrosinase.

PMID- 15976299
TI  - Deep-sea temperature and circulation changes at the Paleocene-Eocene Thermal
      Maximum.
AB  - A rapid increase in greenhouse gas levels is thought to have fueled global
      warming at the Paleocene-Eocene Thermal Maximum (PETM). Foraminiferal
      magnesium/calcium ratios indicate that bottom waters warmed by 4 degrees to 5
      degrees C, similar to tropical and subtropical surface ocean waters, implying no
      amplification of warming in high-latitude regions of deep-water formation under
      ice-free conditions. Intermediate waters warmed before the carbon isotope
      excursion, in association with downwelling in the North Pacific and reduced
      Southern Ocean convection, supporting changing circulation as the trigger for
      methane hydrate release. A switch to deep convection in the North Pacific at the
      PETM onset could have amplified and sustained warming.

PMID- 15976300
TI  - Cleaning the air and improving health with hydrogen fuel-cell vehicles.
AB  - Converting all U.S. onroad vehicles to hydrogen fuel-cell vehicles (HFCVs) may
      improve air quality, health, and climate significantly, whether the hydrogen is
      produced by steam reforming of natural gas, wind electrolysis, or coal
      gasification. Most benefits would result from eliminating current vehicle
      exhaust. Wind and natural gas HFCVs offer the greatest potential health benefits
      and could save 3700 to 6400 U.S. lives annually. Wind HFCVs should benefit
      climate most. An all-HFCV fleet would hardly affect tropospheric water vapor
      concentrations. Conversion to coal HFCVs may improve health but would damage
      climate more than fossil/electric hybrids. The real cost of hydrogen from wind
      electrolysis may be below that of U.S. gasoline.

PMID- 15976301
TI  - Synapses form in skeletal muscles lacking neuregulin receptors.
AB  - The formation of the neuromuscular junction (NMJ) is directed by reciprocal
      interactions between motor neurons and muscle fibers. Neuregulin (NRG) and Agrin
      from motor nerve terminals are both implicated. Here, we demonstrate that NMJs
      can form in the absence of the NRG receptors ErbB2 and ErbB4 in mouse muscle.
      Postsynaptic differentiation is, however, induced by Agrin. We therefore conclude
      that NRG signaling to muscle is not required for NMJ formation. The effects of
      NRG signaling to muscle may be mediated indirectly through Schwann cells.

PMID- 15976302
TI  - Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling.
AB  - Neurogenesis persists in the olfactory bulb (OB) of the adult mammalian brain.
      New interneurons are continually added to the OB from the subventricular zone
      (SVZ) via the rostral migratory stream (RMS). Here we show that secreted
      prokineticin 2 (PK2) functions as a chemoattractant for SVZ-derived neuronal
      progenitors. Within the OB, PK2 may also act as a detachment signal for chain
      migrating progenitors arriving from the RMS. PK2 deficiency in mice leads to a
      marked reduction in OB size, loss of normal OB architecture, and the accumulation
      of neuronal progenitors in the RMS. These findings define an essential role for G
      protein-coupled PK2 signaling in postnatal and adult OB neurogenesis.

PMID- 15976303
TI  - GDF11 controls the timing of progenitor cell competence in developing retina.
AB  - The orderly generation of cell types in the developing retina is thought to be
      regulated by changes in the competence of multipotent progenitors. Here, we show
      that a secreted factor, growth and differentiation factor 11 (GDF11), controls
      the numbers of retinal ganglion cells (RGCs), as well as amacrine and
      photoreceptor cells, that form during development. GDF11 does not affect
      proliferation of progenitors-a major mode of GDF11 action in other tissues-but
      instead controls duration of expression of Math5, a gene that confers competence
      for RGC genesis, in progenitor cells. Thus, GDF11 governs the temporal windows
      during which multipotent progenitors retain competence to produce distinct neural
      progeny.

PMID- 15976305
TI  - Allometry of alarm calls: black-capped chickadees encode information about
      predator size.
AB  - Many animals produce alarm signals when they detect a potential predator, but we
      still know little about the information contained in these signals. Using
      presentations of 15 species of live predators, we show that acoustic features of
      the mobbing calls of black-capped chickadees (Poecile atricapilla) vary with the
      size of the predator. Companion playback experiments revealed that chickadees
      detect this information and that the intensity of mobbing behavior is related to
      the size and threat of the potential predator. This study demonstrates an
      unsuspected level of complexity and sophistication in avian alarm calls.

PMID- 15976304
TI  - Elementary response of olfactory receptor neurons to odorants.
AB  - Signaling by heterotrimeric GTP-binding proteins (G proteins) drives numerous
      cellular processes. The number of G protein molecules activated by a single
      membrane receptor is a determinant of signal amplification, although in most
      cases this parameter remains unknown. In retinal rod photoreceptors, a long-lived
      photoisomerized rhodopsin molecule activates many G protein molecules
      (transducins), yielding substantial amplification and a large elementary (single
      photon) response, before rhodopsin activity is terminated. Here we report that
      the elementary response in olfactory transduction is extremely small. A ligand
      bound odorant receptor has a low probability of activating even one G protein
      molecule because the odorant dwell-time is very brief. Thus, signal amplification
      in olfactory transduction appears fundamentally different from that of
      phototransduction.

PMID- 15976306
TI  - Respiratory muscle responses elicited by dorsal periaqueductal gray stimulation
      in rats.
AB  - The periaqueductal gray matter is an essential neural substrate for central
      integration of defense behavior and accompanied autonomic responses. The dorsal
      half of the periaqueductal gray matter (dPAG) is also involved in mediating
      emotional responses of anxiety and fear, psychological states that often are
      associated with changes in ventilation. However, information regarding
      respiratory modulation elicited from this structure is limited. The present study
      was undertaken to investigate the relationship between stimulus frequency and
      magnitude on ventilatory pattern and respiratory muscle activity in urethane
      anesthetized, spontaneously breathing rats. Electrical stimulation in the dPAG
      recruited abdominal muscle activity increased ventilation and increased
      respiratory frequency by significantly shortening both inspiratory time and
      expiratory time. Ventilation increased within the first breath after the onset of
      stimulation, and the respiratory response increased with increasing stimulus
      frequency and magnitude. dPAG stimulation also increased baseline EMG activity in
      the diaphragm and recruited baseline external abdominal oblique EMG activity,
      normally quiescent during eupneic breathing. Significant changes in
      cardiorespiratory function were only evoked by stimulus intensities >10 microA
      and when stimulus frequencies were >10 Hz. Respiratory activity of both the
      diaphragm and abdominal muscles remained elevated for a minimum of 60 s after
      cessation of stimulation. These results demonstrate that there is a short-latency
      respiratory response elicited from the dPAG stimulation, which includes both
      inspiratory and expiratory muscles. The changes in respiratory timing suggest
      rapid onset and sustained poststimulus dPAG modulation of the brain stem
      respiratory network that includes expiratory muscle recruitment.

PMID- 15976307
TI  - Endogenous central kappa-opioid systems augment renal sympathetic nerve activity
      to maximally retain urinary sodium during hypotonic saline volume expansion.
AB  - Intracerebroventricular injection of kappa-opioid agonists produces diuresis,
      antinatriuresis, and a concurrent increase in renal sympathetic nerve activity
      (RSNA). The present study examined whether endogenous central kappa-opioid
      systems contribute to the renal excretory responses produced by the stress of an
      acute hypotonic saline volume expansion (HSVE). Cardiovascular, renal excretory,
      and RSNA responses were measured during control, acute HSVE (5% body weight, 0.45
      M saline over 30 min), and recovery (70 min) in conscious rats pretreated
      intracerebroventricularly with vehicle or the kappa-opioid receptor antagonist
      nor-binaltorphimine (nor-BNI). In vehicle-pretreated rats, HSVE produced a marked
      increase in urine flow rate but only a low-magnitude and delayed natriuresis.
      RSNA was not significantly suppressed during the HSVE or recovery periods. In nor
      BNI-treated rats, HSVE produced a pattern of diuresis similar to that observed in
      vehicle-treated rats. However, during the HSVE and recovery periods, RSNA was
      significantly decreased, and urinary sodium excretion increased in nor-BNI
      treated animals. In other studies performed in chronic bilateral renal denervated
      rats, HSVE produced similar diuretic and blunted natriuretic responses in animals
      pretreated intracerebroventricularly with vehicle or nor-BNI. Thus removal of the
      renal nerves prevented nor-BNI from enhancing urinary sodium excretion during
      HSVE. These findings indicate that in conscious rats, endogenous central kappa
      opioid systems are activated during hypotonic saline volume expansion to maximize
      urinary sodium retention by a renal sympathoexcitatory pathway that requires
      intact renal nerves.

PMID- 15976308
TI  - Absence of cellular stress in brain after hypoxia induced by arousal from
      hibernation in Arctic ground squirrels.
AB  - Although hypoxia tolerance in heterothermic mammals is well established, it is
      unclear whether the adaptive significance stems from hypoxia or other cellular
      challenge associated with euthermy, hibernation, or arousal. In the present
      study, blood gases, hemoglobin O2 saturation (S(O2), and indexes of cellular and
      physiological stress were measured during hibernation and euthermy and after
      arousal thermogenesis. Results show that arterial O2 tension (Pa(O2)) and S(O2)
      are severely diminished during arousal and that hypoxia-inducible factor (HIF)
      1alpha accumulates in brain. Despite evidence of hypoxia, neither cellular nor
      oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels
      and oxidative modification of biomolecules, was observed during late arousal from
      hibernation. Compared with rats, hibernating Arctic ground squirrels
      (Spermophilus parryii) are well oxygenated with no evidence of cellular stress,
      inflammatory response, neuronal pathology, or oxidative modification following
      the period of high metabolic demand necessary for arousal. In contrast, euthermic
      Arctic ground squirrels experience mild, chronic hypoxia with low S(O2) and
      accumulation of HIF-1alpha and iNOS and demonstrate the greatest degree of
      cellular stress in brain. These results suggest that Arctic ground squirrels
      experience and tolerate endogenous hypoxia during euthermy and arousal.

PMID- 15976309
TI  - A subsidiary fever center in the medullary raphe?
AB  - In fever, as in normal thermoregulation, signals from the preoptic area drive
      both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT).
      Both of these responses are mediated by sympathetic nerves whose premotor neurons
      are located in the medullary raphe. EP3 receptors, key prostaglandin E2 (PGE2)
      receptors responsible for fever induction, are expressed in this same medullary
      raphe region. To investigate whether PGE2 in the medullary raphe might contribute
      to the febrile response, we tested whether direct injections of PGE2 into the
      medullary raphe could drive sympathetic nerve activity (SNA) to BAT and cutaneous
      (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60-180
      nl) into the medullary raphe activated both tail and BAT SNA, as did cooling the
      trunk skin. PGE2 injections (150-500 ng in 300-1,000 nl) into the medullary raphe
      had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast,
      150 ng PGE2 injected into the preoptic area caused large increases in both tail
      and BAT SNA (+60 +/- 17 spikes/15 s and 1,591 +/- 150% of control, respectively),
      increased body temperature (+1.8 +/- 0.2 degrees C), blood pressure (+17 +/- 2
      mmHg), and heart rate (+124 +/- 19 beats/min). These results suggest that despite
      expression of EP3 receptors, neurons in the medullary raphe are unable to drive
      febrile responses of tail and BAT SNA independently of the preoptic area. Rather,
      they appear merely to transmit signals for heat production and heat conservation
      originating from the preoptic area.

PMID- 15976311
TI  - Intracranial bleeding in patients with vertebrobasilar dolichoectasia.
AB  - BACKGROUND AND PURPOSE: Intracranial bleeding in patients with vertebrobasilar
      dolichoectasia (VBD) is considered uncommon, but there are no precise data to
      support this opinion. The purpose of this study was to examine the incidence and
      characteristics of intracranial hemorrhage in patients with VBD and to evaluate
      factors that may promote bleeding. METHODS: We conducted a prospective study of
      156 consecutive VDB patients followed-up for an average 9.35 years. The
      association of demographic, clinical, and imaging features with occurrence of
      intracranial bleeding was evaluated by multivariate analysis. Survival analysis
      was used to evaluate rates of incidence. RESULTS: 32 hemorrhagic strokes were
      observed in 28 patients either as a diagnostic event (n=10) or during follow-up
      (n=22). Of the 32 hemorrhagic events, 6 were subarachnoid hemorrhage and 26
      intraparenchymal hemorrhage. Multivariate analysis found an association between
      intracranial bleeding and maximum diameter of the basilar artery (OR, 4.29;
      P=0.009), degree of lateral displacement of the basilar artery (OR, 4.53;
      P=0.004), hypertension (OR, 4.74; P=0.024), use of antiplatelet or anticoagulant
      agents (OR, 3.07; P=0.033), and female sex (OR 6.33; P=0.001). The cumulative
      proportion of survivors free of hemorrhagic stroke was 88.6 at 5 years and 84.4
      at 10 years. CONCLUSIONS: Our study showed that intracranial bleeding in patients
      with VBD is not as uncommon as usually believed. Its occurrence is associated
      with the degree of ectasia and elongation of the basilar artery and may be
      favored by hypertension and use of antiplatelet or anticoagulant agents.

PMID- 15976312
TI  - Endothelin-1, via ETA receptor and independently of transforming growth factor
      beta, increases the connective tissue growth factor in vascular smooth muscle
      cells.
AB  - Endothelin (ET)-1 is a potent vasoconstrictor that participates in cardiovascular
      diseases. Connective tissue growth factor (CTGF) is a novel fibrotic mediator
      that is overexpressed in human atherosclerotic lesions, myocardial infarction,
      and experimental models of hypertension. In vascular smooth muscle cells (VSMCs),
      CTGF regulates cell proliferation/apoptosis, migration, and extracellular matrix
      (ECM) accumulation. Our aim was to investigate whether ET-1 could regulate CTGF
      and to investigate the potential role of ET-1 in vascular fibrosis. In growth
      arrested rat VSMCs, ET-1 upregulated CTGF mRNA expression, promoter activity, and
      protein production. The blockade of CTGF by a CTGF antisense oligonucleotide
      decreased FN and type I collagen expression in ET-1-treated cells, showing that
      CTGF participates in ET-1-induced ECM accumulation. The ETA, but not ETB,
      antagonist diminished ET-1-induced CTGF expression gene and production. Several
      intracellular signals elicited by ET-1, via ETA receptors, are involved in CTGF
      synthesis, including activation of RhoA/Rho-kinase and mitogen-activated protein
      kinase and production of reactive oxygen species. CTGF is a mediator of TGF-beta-
      and angiotensin (Ang) II-induced fibrosis. In VSMCs, ET-1 did not upregulate TGF
      beta gene or protein. The presence of neutralizing transforming growth factor
      (TGF)-beta antibody did not modify ET-1-induced CTGF production, showing a TGF
      beta-independent regulation. We have also found an interrelationship between Ang
      II and ET-1 because the ETA antagonist diminished CTGF upregulation caused by Ang
      II. Collectively, our results show that, in cultured VSMCs, ET-1, independently
      of TGF-beta and through the activation of several intracellular signals via ETA
      receptors, regulates CTGF. This novel finding suggests that CTGF could be a
      mediator of the profibrotic effects of ET-1 in vascular diseases.

PMID- 15976313
TI  - Proapoptotic, antimigratory, antiproliferative, and antiangiogenic effects of
      commercial C-reactive protein on various human endothelial cell types in vitro:
      implications of contaminating presence of sodium azide in commercial preparation.
AB  - Recent experimental studies suggest C-reactive protein (CRP) may be a potential
      mediator of atherosclerosis and its complications. However, there is growing
      criticism of in vitro CRP studies that use commercial CRP preparations containing
      biologically active contaminants. The effects of commercial CRP, dialyzed
      commercial CRP (dCRP) to remove azide, and sodium azide (NaN3) alone at
      equivalent concentrations to the undialyzed preparation were tested at varying
      concentrations on human umbilical vein endothelial cells (HUVEC), circulating
      endothelial outgrowth cells (EOC), and endothelial progenitor cells (EPC) in
      vitro. CRP and NaN3 alone exhibited equivalent concentration-dependent,
      proapoptotic effects on HUVEC, EOC, and EPC (P<0.01 versus control), whereas dCRP
      had no such effect. Similarly, CRP and NaN3 alone caused equivalent concentration
      dependent decreases in migration, proliferation, and matrigel tube formation
      (P<0.01 versus control) in EOC and HUVEC, whereas dCRP had absolutely no effect
      on these biological functions at any of the concentrations used. We conclude that
      proapoptotic, antiproliferative, antimigratory, and antiangiogenic effects of
      this commercial CRP preparation on a number of endothelial cell phenotypes in
      culture may be explained by the presence of sodium azide in this preparation.
      This study has implications for interpretation of in vitro studies using CRP
      preparations containing azide at equivalent or higher concentrations.

PMID- 15976314
TI  - In vivo and in vitro studies support that a new splicing isoform of OLR1 gene is
      protective against acute myocardial infarction.
AB  - Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the
      OLR1 gene, is a scavenger receptor that plays a fundamental role in the
      pathogenesis of atherosclerosis. LOX-1 activation is associated with apoptosis of
      endothelial cells, smooth muscle cells (SMCs), and macrophages. This process is
      an important underlying mechanism that contributes to plaque instability and
      subsequent development of acute coronary syndromes. Independent association
      genetic studies have implicated OLR1 gene variants in myocardial infarction (MI)
      susceptibility. Because single nucleotide polymorphisms (SNPs) linked to MI are
      located in intronic sequences of the gene, it remains unclear as to how they
      determine their biological effects. Using quantitative real-time PCR and minigene
      approach, we show that intronic SNPs, linked to MI, regulate the expression of a
      new functional splicing isoform of the OLR1 gene, LOXIN, which lacks exon 5.
      Macrophages from subjects carrying the "non-risk" disease haplotype at OLR1 gene
      have an increased expression of LOXIN at mRNA and protein level, which results in
      a significant reduction of apoptosis in response to oxLDL. Expression of LOXIN in
      different cell types results in loss of surface staining, indicating that
      truncation of the C-terminal portion of the protein has a profound effect on its
      cellular trafficking. Furthermore, the proapoptotic effect of LOX-1 receptor in
      cell culture is specifically rescued by the coexpression of LOXIN in a dose
      dependent manner. The demonstration that increasing levels of LOXIN protect cells
      from LOX-1 induced apoptosis sets a groundwork for developing therapeutic
      approaches for prevention of plaque instability.

PMID- 15976316
TI  - Notch-dependent cell cycle arrest is associated with downregulation of
      minichromosome maintenance proteins.
AB  - Perturbation of the Notch signaling pathway has been implicated in the
      pathogenesis of human cardiovascular diseases, and animal models have confirmed
      the requirement of Notch during cardiovascular development. We recently
      demonstrated that Notch activation delays S-phase entry and contributes to
      endothelial contact inhibition. Minichromosome maintenance (MCM) proteins,
      components of the prereplicative complex (pre-RC), are essential for DNA
      replication. Here, we report that Notch-mediated cell cycle arrest is associated
      with downregulation of MCM2 and MCM6 in endothelial cells and human fibroblasts.
      Downregulation of MCM proteins is also observed on activation of C promoter
      binding factor (CBF1) and is mediated by inhibition of Rb phosphorylation, as
      demonstrated using a constitutively active Rb mutant. Although the effects of the
      Notch pathway are cell-type specific and context-dependent, in cell types where
      Notch has an antiproliferative effect, downregulation of MCM proteins may be a
      common mechanism to inhibit DNA replication.

PMID- 15976315
TI  - Differences between left and right ventricular chamber geometry affect cardiac
      vulnerability to electric shocks.
AB  - Although effects of shock strength and waveform on cardiac vulnerability to
      electric shocks have been extensively documented, the contribution of ventricular
      anatomy to shock-induced polarization and postshock propagation and thus, to
      shock outcome, has never been quantified; this is caused by lack of experimental
      methodology capable of mapping 3-D electrical activity. The goal of this study
      was to use optical imaging experiments and 3-D bidomain simulations to
      investigate the role of structural differences between left and right ventricles
      in vulnerability to electric shocks in rabbit hearts. The ventricles were paced
      apically, and uniform-field, truncated-exponential, monophasic shocks of reversed
      polarity were applied over a range of coupling intervals (CIs) in experiment and
      model. Experiments and simulations revealed that reversing the direction of
      externally-applied field (RV- or LV- shocks) alters the shape of the
      vulnerability area (VA), the 2-D grid encompassing episodes of arrhythmia
      induction. For RV- shocks, VA was nearly rectangular indicating little dependence
      of postshock arrhythmogenesis on CI. For LV- shocks, the probability of
      arrhythmia induction was higher for longer than for shorter CIs. The 3-D
      simulations demonstrated that these effects stem from the fact that reversal of
      field direction results in relocation of the main postshock excitable area from
      LV wall (RV- shocks) to septum (LV- shocks). Furthermore, the effect of septal
      (but not LV) excitable area in postshock propagation was found to strongly depend
      on preshock state. Knowledge regarding the location of the main postshock
      excitable area within the 3-D ventricular volume could be important for improving
      defibrillation efficacy.

PMID- 15976317
TI  - Heat shock protein 27 is associated with freedom from graft vasculopathy after
      human cardiac transplantation.
AB  - Experimental studies have suggested that protective genes protect allografts from
      cardiac allograft vasculopathy (CAV), the major complication after cardiac
      transplantation. Here we have sought to confirm this hypothesis using long-term
      heart transplant recipients. Twenty-two patients that were 9 years or older after
      transplant were investigated; 11 of these were without angiographic evidence of
      CAV; 11 had developed early CAV at 1 to 3 years after transplant. To identify
      proteins that may act as protectors from CAV, a global proteomic approach was
      used comparing cardiac biopsies from 12 patients taken within the first 2 weeks
      after transplant and those taken after 9 years from the same patient. Proteins
      were separated by 2-D gel-electrophoresis, detected by silver staining, and
      analyzed using Progenesis software. A particular protein spot was found in 4/6
      biopsies from patients without CAV, but absent from 5/6 biopsies from those with
      CAV (P=0.24); however, quantitative analysis of spot intensity showed a
      significant difference (0.061+/-0.05 versus 0.003+/-0.01, P=0.04). This spot was
      identified by mass spectrometry and a combination of techniques as a
      diphosphorylated form of HSP27. Immunohistochemistry of further biopsies not only
      validated that HSP27 was more abundantly expressed on biopsies without CAV but
      also showed it to be localized to blood vessels. In contrast, vessels from
      patients with CAV did not express HSP27 (P=0.028x10(-4)). Immunohistochemistry of
      12 further early biopsies and nontransplanted heart showed HSP27 to be present in
      normal blood vessels. These findings suggest that expression of a specific
      diphosphorylated form of HSP27 is associated with healthy blood vessels; it
      appears to be lost from vessels of patients with graft vasculopathy.

PMID- 15976318
TI  - Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation.
AB  - Skeletal myoblasts are an attractive cell type for transplantation because they
      are autologous and resistant to ischemia. However, clinical trials of myoblast
      transplantation in heart failure have been plagued by ventricular
      tachyarrhythmias and sudden cardiac death. The pathogenesis of these arrhythmias
      is poorly understood, but may be related to the fact that skeletal muscle cells,
      unlike heart cells, are electrically isolated by the absence of gap junctions.
      Using a novel in vitro model of myoblast transplantation in cardiomyocyte
      monolayers, we investigated the mechanisms of transplant-associated arrhythmias.
      Cocultures of human skeletal myoblasts and rat cardiomyocytes resulted in
      reentrant arrhythmias (spiral waves) that reproduce the features of ventricular
      tachycardia seen in patients receiving myoblast transplants. These arrhythmias
      could be terminated by nitrendipine, an l-type calcium channel blocker, but not
      by the Na channel blocker lidocaine. Genetic modification of myoblasts to express
      the gap junction protein connexin43 decreased arrhythmogenicity in cocultures,
      suggesting a specific means for increasing the safety (and perhaps the efficacy)
      of myoblast transplantation in patients.

PMID- 15976319
TI  - Soluble tissue factor emerges from inflammation.

PMID- 15976320
TI  - Proinflammatory vascular calcification.

PMID- 15976322
TI  - Familial combined hyperlipidemia in Mexicans: association with upstream
      transcription factor 1 and linkage on chromosome 16q24.1.
AB  - OBJECTIVE: To investigate the largely unknown genetic component of the common
      lipid disorder, familial combined hyperlipidemia (FCHL) in Mexicans, we analyzed
      the upstream transcription factor 1 (USF1) gene that was recently associated with
      FCHL and high triglycerides (TG) in Finns. We also analyzed the Mexican FCHL
      families for 26 microsatellite markers residing in the seven chromosomal regions
      on 2p25.1, 9p23, 10q11.23, 11q13, 16q24.1, 19q13, and 21q21, previously linked to
      FCHL in whites. METHODS AND RESULTS: We genotyped 314 individuals in 24 Mexican
      families for 13 SNPs spanning an 88-kb region, including USF1. The FCHL and TG
      traits showed significant evidence for association with 3 SNPs, hCV1459766,
      rs3737787, and rs2073658, and haplotype analyses further supported these findings
      (probability values of 0.05 to 0.0009 for SNPs and their haplotypes). Of these
      SNPs, hCV1459766 is located in the F11 receptor (F11R) gene, located next to
      USF1, making it difficult to exclude. Importantly, the association was restricted
      to a considerably smaller region than in the Finns (14 kb versus 46 kb), possibly
      because of a different underlying linkage disequilibrium structure. In addition,
      1 of the 7 regions, 16q24.1, showed suggestive evidence for linkage (a lod score
      of 2.6) for total cholesterol in Mexicans. CONCLUSIONS: This study, the first to
      extensively investigate the genetic component of the common FCHL disorder in
      Mexicans, provides independent evidence for the role of USF1 in FCHL in an
      outbred population and links the 16q24.1 region to an FCHL-component trait in
      Mexicans.

PMID- 15976321
TI  - New insights into the regulation of HDL metabolism and reverse cholesterol
      transport.
AB  - The metabolism of high-density lipoproteins (HDL), which are inversely related to
      risk of atherosclerotic cardiovascular disease, involves a complex interplay of
      factors regulating HDL synthesis, intravascular remodeling, and catabolism. The
      individual lipid and apolipoprotein components of HDL are mostly assembled after
      secretion, are frequently exchanged with or transferred to other lipoproteins,
      are actively remodeled within the plasma compartment, and are often cleared
      separately from one another. HDL is believed to play a key role in the process of
      reverse cholesterol transport (RCT), in which it promotes the efflux of excess
      cholesterol from peripheral tissues and returns it to the liver for biliary
      excretion. This review will emphasize 3 major evolving themes regarding HDL
      metabolism and RCT. The first theme is that HDL is a universal plasma acceptor
      lipoprotein for cholesterol efflux from not only peripheral tissues but also
      hepatocytes, which are a major source of cholesterol efflux to HDL. Furthermore,
      although efflux of cholesterol from macrophages represents only a tiny fraction
      of overall cellular cholesterol efflux, it is the most important with regard to
      atherosclerosis, suggesting that it be specifically termed macrophage RCT. The
      second theme is the critical role that intravascular remodeling of HDL by lipid
      transfer factors, lipases, cell surface receptors, and non-HDL lipoproteins play
      in determining the ultimate metabolic fate of HDL and plasma HDL-c
      concentrations. The third theme is the growing appreciation that insulin
      resistance underlies the majority of cases of low HDL-c in humans and the
      mechanisms by which insulin resistance influences HDL metabolism. Progress in our
      understanding of HDL metabolism and macrophage reverse cholesterol transport will
      increase the likelihood of developing novel therapies to raise plasma HDL
      concentrations and promote macrophage RCT and in proving that these new
      therapeutic interventions prevent or cause regression of atherosclerosis in
      humans.

PMID- 15976323
TI  - Relationship of monocyte count and peripheral arterial disease: results from the
      National Health and Nutrition Examination Survey 1999-2002.
AB  - BACKGROUND: Although white blood cell (WBC) count has been consistently
      associated with cardiovascular end points, little information is available on the
      independent contribution of specific white blood cell types. The objective of
      this study is to assess the independent association of WBC types and other
      inflammatory markers with the presence of reduced ankle-brachial blood pressure
      index (ABI), a marker of subclinical peripheral arterial disease (PAD). METHODS &
      RESULTS: Cross-sectional study in 3949 individuals > or =40 years of age without
      known cardiovascular disease who participated in the 1999 to 2002 National Health
      and Nutrition Examination Survey (NHANES). PAD was defined as an ABI <0.9 in at
      least 1 leg. After adjustment for traditional cardiovascular risk factors, the
      odds ratios of PAD comparing the highest to the lowest quartiles were 2.24 (95%
      confidence interval 1.24 to 4.04) for monocytes, 1.74 (0.87 to 3.45) for
      neutrophils, 2.53 (1.62 to 3.96) for C-reactive protein, and 2.68 (1.03 to 6.94)
      for fibrinogen. When WBC types and inflammatory markers were simultaneously
      included in the full model, the corresponding odds ratios were 1.91 (95%
      confidence interval 1.06 to 3.42) for monocytes, 1.15 (0.49 to 2.69) for
      neutrophils, 1.37 (0.75 to 2.49) for C-reactive protein, and 2.21 (0.88 to 5.57)
      for fibrinogen. CONCLUSIONS: Monocytes were the only WBC type significantly and
      independently associated with PAD in a representative sample of the U.S.
      population after adjustment for other inflammatory markers. These findings
      reflect the potential role of circulating monocyte counts as markers of
      atherosclerosis.

PMID- 15976324
TI  - Atherosclerosis in patients with autoimmune disorders.
AB  - Recent findings indicate that presence of activated immune competent cells and
      inflammation are typical of atherosclerosis, the main cause of cardiovascular
      disease (CVD). The risk of CVD is very high in a prototypic autoimmune disease,
      systemic lupus erythematosus (SLE), and is also raised in other autoimmune
      diseases such as rheumatoid arthritis. Autoimmunity-related CVD and
      atherosclerosis are important clinical problems. They may also shed light on
      interactions between immune reactions and atherosclerosis development and
      manifestations, not least in women, who have a much higher risk of autoimmune
      disease than men. In general, a combination of traditional and nontraditional
      risk factors, including dyslipidemia (and to a varying degree, hypertension,
      diabetes, and smoking), inflammation, antiphospholipid antibodies (aPLs), and
      lipid oxidation, contribute to CVD in autoimmune diseases. Premature
      atherosclerosis is likely to be a major underlying mechanism, although
      distinctive features, if any, of autoimmunity-related atherosclerosis compared
      with "normal" atherosclerosis are not clear. One interesting possibility is that
      factors such as inflammation, neoepitopes on endothelial cells, or aPLs make
      atherosclerotic lesions in autoimmune disease more prone to rupture than in
      "normal" atherosclerosis. Some cases of autoimmunity-related CVD may be more
      related to thrombosis than atherosclerosis. Whether premature atherosclerosis is
      a general feature of autoimmune diseases such as SLE or only affects a subgroup
      of patients whereas others do not have an increased risk remains to be
      demonstrated. Treatment of patients with autoimmune disease should also include
      CVD aspects and be focused on traditional risk factors as well as on disease
      related factors. Hopefully novel therapeutic principles will be developed that
      target the causes of the inflammation present in atherosclerotic lesions.

PMID- 15976325
TI  - Protective mechanisms of inosine in platelet activation and cerebral ischemic
      damage.
AB  - OBJECTIVE: Inosine is a naturally occurring nucleoside degraded from adenosine.
      Recent studies have demonstrated that inosine has potent immunomodulatory and
      neuroprotective effects. In the present study, we further investigated the
      inhibitory effects of inosine on platelet activation in vitro and in vivo, as
      well as in attenuating middle cerebral artery occlusion (MCAO)-induced focal
      cerebral ischemia in rats. METHODS AND RESULTS: Inosine concentration-dependently
      (0.5 to 6.0 mmol/L) inhibited platelet aggregation stimulated by agonists.
      Inosine (1.5 and 3.0 mmol/L) inhibited phosphoinositide breakdown, [Ca+2]i, and
      TxA2 formation in human platelets stimulated by collagen (1 microg/mL). In
      addition, inosine (1.5 and 3.0 mmol/L) markedly increased levels of cyclic
      guanylate monophosphate (GMP) and cyclic GMP-induced vasodilator-stimulated
      phosphoprotein Ser157 phosphorylation. Rapid phosphorylation of a platelet
      protein of molecular weight 47,000 (P47), a marker of protein kinase C
      activation, was triggered by collagen (1 microg/mL). This phosphorylation was
      markedly inhibited by inosine (3.0 mmol/L). Inosine (1.5 and 3.0 mmol/L) markedly
      reduced hydroxyl radical in collagen (1 microg/mL)-activated platelets. In in
      vivo studies, inosine (400 mg/kg) significantly prolonged the latency period of
      inducing platelet plug formation in mesenteric venules of mice, and
      administration of 2 doses (100 mg/kg) or a single dose (150 mg/kg) of inosine
      significantly attenuated MCAO-induced focal cerebral ischemia in rats.
      CONCLUSIONS: Platelet aggregation contributes significantly to MCAO-induced focal
      cerebral ischemia. The most important findings of this study suggest that inosine
      markedly inhibited platelet activation in vitro and in vivo, as well as cerebral
      ischemia. Thus, inosine treatment may represent a novel approach to lowering the
      risk of or improving function in thromboembolic-related disorders and ischemia
      reperfusion brain injury.

PMID- 15976326
TI  - Mast cell tryptase in mast cell granules enhances MCP-1 and interleukin-8
      production in human endothelial cells.
AB  - OBJECTIVE: Recent studies have highlighted the pathogenetic importance of chronic
      inflammation in cardiovascular disorders such as congestive heart failure and
      atherosclerosis. Mast cells release a wide variety of immune mediators that may
      initiate inflammatory responses, whereas endothelial cells (ECs) play a prominent
      role in the pathogenesis of cardiovascular diseases by secreting cytokines. The
      purpose of this study was to clarify the role of mast cells as an activator of
      ECs. METHODS AND RESULTS: ECs harvested from human umbilical cord veins were
      stimulated with mast cell granules (MCGs) prepared from sonicated human leukemic
      mast cells. The supernatants and total RNA from cells were collected. Levels of
      interleukin (IL)-1beta, tumor necrosis factor-alpha, and granulocyte colony
      stimulating factor remained unchanged up to 24 hours. In contrast, levels of
      monocyte chemoattractant protein-1 (MCP-1) and IL-8 increased significantly
      within 6 hours. Northern blot analysis revealed an increase in MCP-1 and IL-8
      mRNA expression in MCG-treated ECs. Induction of these chemokines was attenuated
      by antitryptase neutralizing antibody. Furthermore, MCP-1 and IL-8 were induced
      in ECs by incubation with human mast cell tryptase, but not with chymase.
      CONCLUSIONS: These results indicate that the production of MCP-1 and IL-8 in ECs
      was induced by MCG and amplified by tryptase.

PMID- 15976327
TI  - Caveolin-1 is essential for activation of Rac1 and NAD(P)H oxidase after
      angiotensin II type 1 receptor stimulation in vascular smooth muscle cells: role
      in redox signaling and vascular hypertrophy.
AB  - OBJECTIVE: Angiotensin II (Ang II) is a potent mediator of vascular hypertrophy
      in vascular smooth muscle cells (VSMCs). These effects are mediated through the
      Ang II type 1 receptor (AT1R) and require its trafficking through caveolin-1
      (Cav1)-enriched lipid rafts and reactive oxygen species (ROS) derived from Rac1
      dependent NAD(P)H oxidase. The specific role(s) of Cav1 in AT1R signaling is
      incompletely understood. METHODS AND RESULTS: Knockdown of Cav1 protein by small
      interfering RNA (siRNA) inhibits Ang II-stimulated Rac1 activation and membrane
      translocation, H2O2 production, ROS-dependent epidermal growth factor receptor
      (EGF-R) transactivation, and subsequent phosphorylation of Akt without affecting
      ROS-independent extracellular signal-regulated kinase 1/2 phosphorylation. Ang II
      stimulates tyrosine phosphorylation of Sos-1, a Rac-guanine nucleotide exchange
      factor, which is inhibited by Cav1 siRNA, demonstrating involvement of Cav1 in
      Rac1 activation. Detergent-free fractionation showed that EGF-Rs are found
      basally in Cav1-enriched lipid raft membranes and associate with Cav1. Ang II
      stimulates AT1R movement into these microdomains contemporaneously with the
      egress of EGF-R. Both aspects of this bidirectional receptor trafficking are
      inhibited by Cav1 siRNA. Moreover, Cav1 siRNA inhibits Ang II-induced vascular
      hypertrophy. CONCLUSIONS: Cav1 plays an essential role in AT1R targeting into
      Cav1-enriched lipid rafts and Rac1 activation, which are required for proper
      organization of ROS-dependent Ang II signaling linked to VSMC hypertrophy.

PMID- 15976328
TI  - Genetic deletion or antibody blockade of alpha1beta1 integrin induces a stable
      plaque phenotype in ApoE-/- mice.
AB  - OBJECTIVE: Adhesive interactions between cells and the extracellular matrix play
      an important role in inflammatory diseases like atherosclerosis. We investigated
      the role of the collagen-binding integrin alpha1beta1 in atherosclerosis. METHODS
      AND RESULTS: ApoE-/- mice were alpha1-deficient or received early or delayed anti
      alpha1 antibody treatment. Deficiency in alpha1 integrin reduced the area of
      atherosclerotic plaques and altered plaque composition by reducing inflammation
      and increasing extracellular matrix. In advanced plaques, alpha1-deficient mice
      had a reduced macrophage and CD3+ cell content, collagen and smooth muscle cell
      content increased, lipid core sizes decreased, and cartilaginous metaplasia
      occurred. Anti-alpha1 antibody treatment reduced the macrophage content in
      initial plaques after early and delayed treatment, decreased the CD3+ cell
      content in advanced plaques after delayed treatment, and increased the collagen
      content in initial and advanced plaques after delayed treatment. Migration assays
      performed on alpha1-deficient macrophages on collagen I and IV substrata revealed
      that alpha1-deficient cells can migrate on collagen I, but not IV. Anti-alpha1
      antibody treatment of ApoE-/- macrophages also inhibited migration of cells on
      collagen IV. CONCLUSIONS: Our results suggest that alpha1beta1 integrin is
      involved in atherosclerosis by mediating the migration of leukocytes to lesions
      by adhesion to collagen IV. Blocking this integrin reduces atherosclerosis and
      induces a stable plaque phenotype.

PMID- 15976329
TI  - Recurrence rate after a first venous thrombosis in patients with familial
      thrombophilia.
AB  - OBJECTIVE: Few comprehensive data are available on the recurrence rate of venous
      thrombosis in carriers of thrombophilic defects from thrombophilic families. We
      prospectively determined the recurrence rate after a first venous thrombotic
      event in patients with familial thrombophilia attributable to factor V Leiden or
      deficiencies of protein C, S, or antithrombin. METHODS AND RESULTS: Data were
      gathered during follow-up on the occurrence of risk situations, anticoagulation
      treatment, and events (eg, venous thrombosis, hemorrhage). Over a mean follow-up
      period of 5.6 years, 44 of the 180 patients with familial thrombophilia who did
      not use long-term anticoagulation experienced a recurrent venous thromboembolic
      event (5.0%/year; 95% CI 3.6 to 6.7) compared with 7 of the 124 patients on long
      term anticoagulation (1.1%/year; 95% CI 0.4 to 2.2). Spontaneous events occurred
      less often in patients on long-term anticoagulation (57%) than in patients
      without long-term anticoagulation (75%). The highest recurrence rate was found
      among men with a deficiency in natural anticoagulants or multiple defects and
      women with antithrombin deficiency. Although long-term anticoagulation treatment
      decreased the incidence of recurrent events by 80%, it also resulted in a risk of
      major hemorrhage of 0.8% per year. CONCLUSIONS: Extra care after a first event is
      required for men with a deficiency in natural anticoagulants or multiple defects
      and women with antithrombin deficiency.

PMID- 15976330
TI  - Important role of apoptosis signal-regulating kinase 1 in ischemia-induced
      angiogenesis.
AB  - OBJECTIVE: We first examined the role of apoptosis signal-regulating kinase 1
      (ASK1), one of mitogen-activated protein kinase kinase kinases, in ischemia
      induced angiogenesis. METHODS AND RESULTS: Unilateral hindlimb ischemia was
      induced surgically in C57BL/6J wild-type (WT) mice or mice deficient in ASK1
      (ASK1(-/-)). ASK1 activity in WT mouse hindlimb was increased dramatically after
      ischemia. By laser Doppler analysis, well-developed collateral vessels and
      angiogenesis were observed in WT mice in response to hindlimb ischemia, whereas
      these responses were reduced in ASK1(-/-) mice. Immunostaining revealed that
      infiltration of macrophages and T lymphocytes was suppressed in the ischemic
      tissues of ASK1(-/-) mice compared with WT mice. The expression of vascular
      endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)
      proteins in ischemic tissues was weaker in ASK1(-/-) mice compared with WT mice.
      In vitro study on endothelial cells indicated that dominant-negative ASK1
      significantly attenuated hydrogen peroxide-induced VEGF and MCP-1 production.
      Furthermore, in vivo blockade of MCP-1 by its neutralizing antibody suppressed
      the recovery of the blood flow and capillary formation after ischemia.
      CONCLUSIONS: ASK1 pathway promotes early angiogenesis by inducing inflammatory
      cell infiltration and VEGF and MCP-1 expression. ASK1 may provide the basis for
      the development of new therapeutic strategy for angiogenesis.

PMID- 15976332
TI  - Biofilm formation and esp gene carriage in enterococci.
AB  - AIMS: To investigate biofilm production and esp carriage in enterococci. METHODS:
      Biofilm production in vancomycin resistant enterococci (VRE) and vancomycin
      susceptible enterococci (VSE) was tested on a microtitre plate method, using both
      brain heart infusion (BHI) broth and human serum as media. Isolates were screened
      for the esp gene, which has been reported to be essential for biofilm formation
      in enterococci, by means of the polymerase chain reaction. RESULTS: None of seven
      VRE and nine of 28 VSE tested formed a biofilm. One initially negative VRE
      Enterococcus faecium isolate produced a strong biofilm after 21 weeks of dry
      starvation on a cotton swab. By Fisher's exact test, there was no significant
      difference in biofilm formation between VRE and VSE, E faecalis and E faecium, or
      isolates from different sites. Biofilm formation was independent of possession of
      the esp gene. One isolate produced a strong biofilm in human serum but only a
      weak biofilm in BHI, whereas another produced a moderate biofilm in human serum
      but a weak biofilm in BHI. CONCLUSIONS: The acquisition of vancomycin resistance
      may result in a lower ability to form biofilms, but a larger study using clinical
      isolates is needed to test this hypothesis. That one initially negative VRE
      isolate produced a strong biofilm after prolonged dry starvation suggests that
      biofilm formation may be an adaptive response. The esp gene does not appear to be
      necessary or sufficient for production of biofilms in enterococci.

PMID- 15976331
TI  - Molecular pathology of prostate cancer.
AB  - The molecular pathology of prostate cancer is complex; not only are multiple
      genes involved in its pathogenesis, but additional environmental factors such as
      diet and inflammation are also involved. The exhaustive research into prostate
      cancer to date has demonstrated a complex interaction of multiple genes and
      environmental factors, some of which may be more important in individual prostate
      cancer cases. This is an exciting era, with the emergence of new investigative
      tools such as DNA microarray technology and the application of the field of
      proteomics to the study of human cancers. Knowledge of genetic changes underlying
      the initiation, development, and progression of prostate cancer is accumulating
      rapidly. With increasing knowledge, it may be possible to distinguish indolent
      from aggressive prostate tumours by molecular fingerprinting. This review
      discusses the most consistently reported molecular pathological findings in
      hereditary and sporadic prostate cancer, together with new concepts and
      technologies.

PMID- 15976333
TI  - Human defensin 5 expression in intestinal metaplasia of the upper
      gastrointestinal tract.
AB  - BACKGROUND: Upper gastrointestinal tract intestinal metaplasia (IM) is termed
      Barrett's oesophagus (BO) or gastric intestinal metaplasia (GIM), depending on
      its location. BO and GIM are associated with chemical exposure resulting from
      gastro-oesophageal reflux and chronic Helicobacter pylori infection,
      respectively. Paneth cells (PCs), characterised by cytoplasmic eosinophilic
      granules, are found in a subset of IM at these sites, but histology may not
      accurately detect them. AIM: To determine human defensin 5 (HD5; an antimicrobial
      peptide produced by PCs) expression in BO and GIM, and to investigate its
      association with H pylori infection. METHODS: Endoscopic biopsies from 33
      patients with BO and 51 with GIM, and control tissues, were examined by routine
      histology and for H pylori infection and HD5 mRNA and protein expression.
      RESULTS: In normal tissues, HD5 expression was specific for PCs in the small
      intestine. Five patients with BE and 42 with GIM expressed HD5, but few HD5
      expressing cells in IM had the characteristic histological features of PCs. Most
      HD5 positive specimens were H pylori infected and most HD5 negative specimens
      were not infected. CONCLUSIONS: HD5 immunohistochemistry was often positive in IM
      when PCs were absent by conventional histology. Thus, HD5 immunohistochemistry
      may be superior to histology for identifying metaplastic PCs and distinguishing
      GIM from BO. The higher frequency of HD5 expression in GIM than in BO is
      associated with a higher frequency of H pylori infection, suggesting that in IM
      PCs may form part of the mucosal antibacterial response.

PMID- 15976334
TI  - Immunocytochemical detection of deoxycytidine kinase in haematological
      malignancies and solid tumours.
AB  - BACKGROUND: Deoxycytidine kinase (dCK) is responsible for the activation of
      several clinically important deoxynucleoside analogues used for the treatment of
      haematological and solid malignancies. AIM: To measure dCK expression in tumour
      cells from different origins. METHOD: A rabbit antihuman dCK antibody was used
      for the immunocytochemical detection of dCK expression in three leukaemic cell
      lines (HL60, U937, and CCRF-CEM) and 97 patient samples (paediatric acute myeloid
      leukaemia (AML) and lymphoid leukaemia (ALL), retinoblastoma, paediatric brain
      tumours, and adult non-small cell lung cancer (NSCLC)). RESULTS: CCRF-CEM, U937,
      and HL60 cells stained positively for dCK and the degree of expression correlated
      with dCK activity. dCK expression varied between tumour types and between
      individual patients within one tumour type. dCK was located predominantly in the
      cytoplasm. The staining intensity was scored as negative (0), low (1+),
      intermediate (2+), or high (3+). Expression of dCK was high in AML blasts. In
      contrast, brain tumour samples expressed low amounts of dCK. dCK staining ranged
      from low (1+) to high (3+) in ALL blasts, retinoblastoma, and NSCLC tissue
      samples. Staining was consistent (interobserver variability, 88%; kappa = 0.83)
      and specific. Western blotting detected the dCK protein appropriately at 30 kDa,
      without additional bands. CONCLUSIONS: Immunocytochemistry is an effective and
      reliable method for determining the expression of dCK in patient samples and
      requires little tumour material. This method enables large scale screening of dCK
      expression in tumour samples.

PMID- 15976335
TI  - Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR
      (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase
      inhibitors?
AB  - BACKGROUND: Metaplastic carcinomas (MCs) of the breast rarely express steroid
      receptors and Her-2, which minimises the options for adjuvant treatment in
      patients with advanced disease. AIMS: To investigate the possible eligibility of
      patients with MCs for epidermal growth factor receptor (EGFR) targeted treatment.
      METHODS: Immunohistochemical assessment of the expression of steroid receptors
      and four members of the EGFR/Her family (EGFR/Her-1-4) in 20 MCs (eight with
      heterologous elements, seven spindle cell MCs, four carcinosarcomas, and one
      matrix producing carcinoma). Fourteen of the 20 MCs were positive for EGFR (Her
      1). Among these cases, 1+, 2+, and 3+ reactivity were seen in two, four, and
      eight cases, respectively. Her-2 was only present in one MC with 1+ reactivity.
      Her-3 (1+ reactivity), Her-4 (2+ reactivity), and the androgen receptor (2+
      reactivity) were also expressed by one tumour. Oestrogen and progesterone
      receptors (3+ reactivity each) were detected in the epithelial component only of
      two carcinosarcoma-type MCs. CONCLUSIONS: MCs express EGFR considerably more
      frequently than the types of breast carcinomas that have been investigated
      previously. Although molecular analyses for possible genetic alterations in the
      EGFR might be required, these results suggest that women suffering from this
      aggressive form of breast carcinoma might benefit from treatment with protein
      kinase inhibitors, such as gefitinib.

PMID- 15976336
TI  - Pathological diagnosis of columnar cell lesions of the breast: are there issues
      of reproducibility?
AB  - AIMS: To assess inter/intraobserver variability in the interpretation of a series
      of digitised images of columnar cell lesions (CCLs) of the breast. METHODS: After
      a tutorial on breast CCL, 39 images were presented to seven staff pathologists,
      who were instructed to categorize the lesions as follows: 0, no columnar cell
      change (CCC) or ductal carcinoma in situ (DCIS); 1, CCC; 2, columnar cell
      hyperplasia; 3, CCC with architectural atypia; 4, CCC with cytological atypia; 5,
      DCIS. Concordance with the tutor's diagnosis and degree of agreement among
      pathologists for each image were determined. The same set of images was re
      presented to the pathologists one week later, their diagnoses collated, and
      inter/intraobservor reproducibility and level of agreement for individual images
      analysed. RESULTS: Diagnostic reproducibility with the tutor ranged from moderate
      to substantial (kappa values, 0.439-0.697) in the first exercise. At repeat
      evaluation, intraobserver agreement was fair to perfect (kappa values, 0.271
      0.832), whereas concordance with the tutor varied from fair to substantial (kappa
      values, 0.334-0.669). There was unanimous agreement on more images during the
      second exercise, mainly because of agreement on the diagnosis of DCIS. The lowest
      agreement was seen for CCC with cytological atypia. CONCLUSIONS: Interobserver
      and intraobserver agreement is good for DCIS, but more effort is needed to
      improve diagnostic consistency in the category of CCC with cytological atypia.
      Continued awareness and study of these lesions are necessary to enhance
      recognition and understanding.

PMID- 15976337
TI  - HER2 amplification status in breast cancer: a comparison between
      immunohistochemical staining and fluorescence in situ hybridisation using manual
      and automated quantitative image analysis scoring techniques.
AB  - AIMS: To compare the results of breast cancer sections with HercepTesttrade mark
      immunohistochemistry (IHC) scores ranging from 0 to 3+ with fluorescence in situ
      hybridisation (FISH) for HER2 amplification. The HER2 digital scoring application
      of the Micrometastasis Detection System (MDS) was used, together with manual
      scoring of FISH and HercepTest, to determine whether this system provides an
      accurate alternative. METHODS: Paraffin wax embedded sections were stained using
      HercepTest and analysed by eye and automated quantitative image analysis. FISH
      was performed using the PathVysion fluorescent probe and scored by eye and
      automated quantitative image analysis using MDS. RESULTS: Of 114 cases, 26% were
      amplified by FISH, whereas only 18% scored 3+; 32% of IHC 2+ cases were amplified
      by FISH, and one showed borderline amplification. Six percent of IHC negative
      cases (0 or 1+) were amplified by FISH, and one showed borderline amplification.
      Of IHC 3+ cases, 10% were non-amplified by FISH. Classification discrepancies
      were seen in 18% of HercepTest cases scored by eye and using the MDS system. MDS
      was consistent with visual FISH scoring and correctly differentiated most
      ambiguous visual IHC scores. CONCLUSIONS: FISH provides a more accurate and
      consistent scoring system for determining HER2 amplification than HercepTest. The
      MDS system provides a reliable, consistent alternative to visual IHC and FISH
      scoring. IHC is still a valuable technique to aid in identification of isolated
      or heterogeneous tumour populations for subsequent FISH analysis, and a combined
      FISH and HercepTest approach to all breast cancer cases may be the most efficient
      strategy.

PMID- 15976338
TI  - The use of LYVE-1 antibody for detecting lymphatic involvement in patients with
      malignant melanoma of known sentinel node status.
AB  - BACKGROUND: Sentinel node (SN) status is the most important prognostic indicator
      in patients with cutaneous melanoma without clinically evident metastatic spread,
      but the procedure is associated with considerable morbidity. The LYVE-1 lymphatic
      marker offers the possibility of studying lymphangiogenesis and tumour metastasis
      within the primary excision. AIMS: To establish whether lymphatic vessel
      numbers/distribution within the primary tumour correlated with SN status. To
      assess whether tumour cells were easily demonstrable within lymphatics and could
      be used as a surrogate for SN status. METHODS: Double immunostaining for LYVE-1
      and S100 in cutaneous biopsies from 18 SN+ patients with no lymphatic/vascular
      involvement on routine histology and 18 SN- patients matched for tumour thickness
      and ulceration. RESULTS: Lymphatic vessels were detected in all cases. Vessels
      within the tumour mass were suggestive of active lymphangiogenesis; those outside
      were mainly mature vessels with well defined walls. Tumour cells within
      lymphatics were detected in one of 18 SN- and five of 18 SN+ patients. Lymphatics
      containing tumour cells were all outside the tumour mass in well formed vessels,
      suggesting melanoma cell invasion into preformed lymphatics. There was no
      significant difference in lymphatic counts between SN+ and SN- patients. Although
      peritumorous lymphatic counts were higher in ulcerated than non-ulcerated
      melanomas, they did not vary with Breslow thickness. CONCLUSION: LYVE-1 staining
      can reliably demonstrate lymphatic vessel distribution, but lymphatic counts
      cannot predict melanoma metastatic potential and cannot substitute for SN biopsy.
      LYVE-1 immunostaining can detect melanoma cells within lymphatics, but is
      unreliable in predicting melanoma metastasis, failing to detect metastatic spread
      in more than two thirds of patients with regional node metastasis.

PMID- 15976339
TI  - Cytokeratin phenotyping does not help in distinguishing oesophageal
      adenocarcinoma from cancer of the gastric cardia.
AB  - BACKGROUND: It is sometimes difficult to distinguish between cardia cancer and
      oesophageal cancer. AIMS: To evaluate whether cytokeratin (CK) expression of the
      tumour can be of value in differentiating between the two tumour types. METHODS:
      Consecutive patients with a malignant tumour in the oesophagus or stomach were
      recruited. Biopsy specimens were taken for routine haematoxylin and eosin
      staining. One tissue block with representative tissue was selected for
      immunohistochemical staining (CK7 and CK20). RESULTS: Endoscopically located
      adenocarcinoma of the oesophagus was present in 84 patients (64 men, 20 women;
      mean age, 68 years; range, 44-91). Cancer located primarily in the gastric cardia
      was present in 63 patients (42 men, 21 women; mean age, 68 years; range, 42-88).
      The histological diagnosis was metastasis from a primary tumour outside the
      oesophagus or stomach in 19 patients. The patients were divided into three groups
      for the immunohistochemical analysis. Patients in group A had definite
      oesophageal cancer, group B patients had a definite carcinoma located in the
      gastric cardia, and group C patients had an obstructing tumour distal in the
      oesophagus at the level of the diaphragm, which could not be passed with the
      endoscope. Paraffin wax embedded material was available from 122 patients for
      immunostaining and CK analysis. There was no significant difference in expression
      or distribution of CK7 or CK20 in the three groups of patients. CONCLUSION: CK
      phenotyping cannot distinguish between cancer arising from a Barrett's oesophagus
      and carcinoma originating in the gastric cardia.

PMID- 15976340
TI  - The presence of benign prostatic glandular tissue at surgical margins does not
      predict PSA recurrence.
AB  - BACKGROUND: Serum prostate specific antigen (PSA) increases after radical
      prostatectomy are thought to indicate recurrent disease, although some suggest
      they result from benign prostatic epithelial tissue left at surgical margins.
      AIMS: To investigate whether presence, location, and extent of benign prostatic
      tissue at radical prostatectomy surgical margins influence patient outcome.
      METHODS: One hundred and ninety nine patients with prostate cancer and negative
      surgical margins were studied. The prostectomy specimens were totally embedded
      using the whole mount technique. The apex and bladder neck, dissected as a cone
      from the specimen, were serially sectioned. The total length of benign prostatic
      tissue at the margins, measured for each location using an ocular micrometer, was
      obtained by summing the length of all positive sites. The presence, anatomical
      location, and extent of benign prostatic tissue at the margin were correlated
      with clinicopathological characteristics and postoperative PSA increases.
      RESULTS: Fifty five cases had benign prostatic glandular tissue at the surgical
      margin. The mean length was 2.19 mm (0.1-14.7). The most frequent location of
      benign prostatic tissue was the apex (40 patients). Presence, anatomical
      location, and length of benign prostatic tissue at the margin were not
      significantly associated with age, preoperative PSA, prostate weight,
      pathological stage, tumour volume, largest tumour dimension, Gleason score,
      extraprostatic extension, seminal vesical invasion, tumour multifocality,
      perineural invasion, or PSA recurrence. CONCLUSIONS: Benign prostatic tissue was
      frequently found in margins of apex and bladder base, but uncommon in the
      anterior or posterior prostate. The presence of benign prostatic tissue at
      surgical margins had no prognostic relevance.

PMID- 15976341
TI  - Antibiotic selection patterns in acutely febrile new outpatients with or without
      immediate testing for C reactive protein and leucocyte count.
AB  - BACKGROUND: Excessive use of broad spectrum antibiotics is related to the spread
      of drug resistant bacterial strains in the community. AIM/METHODS: The effects of
      immediate testing for C reactive protein (CRP) and white blood cell count (WBC)
      on physicians' choices of antibiotic was investigated in patients with acute
      infection. Acutely febrile new outpatients were randomised into two groups: group
      1 (147 patients) underwent CRP and WBC testing before initial consultation
      (advance testing). Prescriptions were compared with those in group 2 (no advance
      testing; 154 patients). RESULTS: In non-pneumonic acute respiratory tract
      infections, 61 (58%) and 122 (91%) of group 1 and 2 patients were prescribed
      antibiotics, respectively. Cefcapene pivoxil (third generation cephalosporin) and
      amoxicillin were the most frequently chosen drugs for group 1 and 2,
      respectively. Total prescriptions of newer, extended spectrum antibiotics
      (cefcapene pivoxil and clarithromycin (advanced macrolide)) were reduced by 25%
      in group 1, although they increased in rate (41 (67%) v 55 (45%) prescriptions)
      because of the decreased prescription of amoxicillin. In group 1, cefcapene
      pivoxil was preferentially selected when WBC values were greater than 9 x
      10(9)/litre. Prescription shifted to macrolides (mainly clarithromycin) in
      patients without leucocytosis. Patient treatment outcome did not significantly
      differ between the two groups. CONCLUSIONS: The availability of CRP and WBC data
      during initial consultation greatly reduced prescription of amoxicillin, but had
      a lesser effect on newer, potent, broad spectrum antibiotics.

PMID- 15976342
TI  - Cell cycle related proteins as prognostic parameters in radically resected non
      small cell lung cancer.
AB  - BACKGROUND: Experimental evidence suggests that lung cancer development and
      progression can be linked to an increased proliferation rate. AIMS/METHODS: To
      evaluate the immunohistochemical expression of seven components of the cell cycle
      machinery in a series of well characterised non-small cell lung cancer (NSCLC)
      specimens (n = 105). RESULTS: Multivariate analysis revealed that simultaneous
      loss of expression of three of these factors--cyclin D1, the cyclin dependent
      kinase inhibitor p16, and the tumour suppressor retinoblastoma protein Rb2/p130-
      correlated with survival, confirming the hypothesis that the cyclin D1-p16
      retinoblastoma tumour suppressor pathway is inactivated in most lung cancer
      samples. CONCLUSIONS: These results suggest that loss of control of cell cycle
      checkpoints is a common occurrence in lung cancer and support the idea that
      functional cooperation between different cell cycle regulatory proteins
      constitutes another level of regulation in cell growth control and tumour
      suppression.

PMID- 15976343
TI  - Polymorphism of the 5' flanking region of the IL-12 receptor beta2 gene partially
      determines the clinical types of leprosy through impaired transcriptional
      activity.
AB  - BACKGROUND: Individual differences in T cell responsiveness to interleukin 12 (IL
      12), resulting from inherited factors, may be responsible for differences in the
      intensity of cell mediated immune (CMI) responses in patients with leprosy, a
      disease with a wide clinical spectrum. AIM: Polymorphisms in the 5' flanking
      region of the IL12RB2 gene were analysed to determine potential immunogenetic
      factors affecting CMI responses, using leprosy as a model. METHODS: Polymorphisms
      in the 5' flanking region of IL12RB2 were examined using direct sequencing
      techniques, and allele frequencies between patients with lepromatous leprosy and
      patients with tuberculoid leprosy were compared. The effect of these single
      nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the
      dual luciferase reporter gene assay in Jurkat T cells. RESULTS: Several SNPs,
      including -1035A>G, -1023A>G, -650delG, and -465A>G, were detected within the 5'
      flanking region of IL12RB2. The frequency of haplotype 1 (-1035A, -1023A, -650G, 
      464A) was high in the general Japanese population, but was significantly lower in
      lepromatous patients compared with tuberculoid patients and healthy controls.
      Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying
      one or more SNP exhibited a lower transcriptional activity compared with
      haplotype 1. CONCLUSION: SNPs within the 5' flanking region of IL12RB2 affect the
      degree of expression of this gene and may be implicated in individual differences
      in CMI responsiveness to mycobacterial antigens, leading to lepromatous or
      tuberculoid leprosy.

PMID- 15976344
TI  - Survivability of vancomycin resistant enterococci and fitness cost of vancomycin
      resistance acquisition.
AB  - AIMS: To investigate the survivability of vancomycin resistant enterococci (VRE)
      under dry starvation conditions and the fitness cost of vancomycin resistance.
      METHODS: VRE colonies on cotton swabs were incubated at room temperature in a
      sterile box and cultured weekly until cultures no longer showed growth. Negative
      swabs inoculated into brain heart infusion (BHI) broth were subcultured to blood
      agar after 24, 48, and 72 hours of incubation to resuscitate viable but non
      culturable cells. Stability of the vancomycin resistance determinant and of the
      DNA fingerprint pattern was determined by multiplex polymerase chain reaction
      (PCR) and repetitive PCR, respectively. Tests for fitness cost were carried out
      on the same VRE isolates and 28 hospital vancomycin sensitive enterococci (VSE)
      isolates by incubation and measurement of optical density using a microplate
      reader and comparing maximum growth rate and lag phase duration between VRE and
      VSE, using independent samples t tests. RESULTS: Mean maximum time of recovery by
      primary culture was 8.5 weeks for Enterococcus faecalis VRE and 21.8 weeks for E.
      faecium VRE. Two of two E. faecalis isolates were resuscitated after 24 hours in
      BHI broth, and two of five E. faecium isolates after 72 hours. No fitness cost of
      vancomycin resistance was demonstrated. CONCLUSIONS: VRE can survive for
      prolonged periods in a dry starvation state, retaining their genetic complement,
      including vancomycin resistance determinants, and show little or no fitness cost
      of vancomycin resistance. Thus, the rate of entry required for VRE to become, and
      remain, endemic in the community is relatively small.

PMID- 15976346
TI  - Transformed dermatofibrosarcoma protuberans: a clinicopathological study of eight
      cases.
AB  - BACKGROUND: Fibrosarcomatous (FS) or malignant fibrous histiocytomatous (MFH)
      transformation of dermatofibrosarcoma protuberans (DFSP) is a rare, but well
      known, entity. DFSPs with sarcomatous areas have questionable biological
      behaviour. Several studies suggest that they have a higher risk for local
      recurrence and distant metastases than ordinary DFSPs. One recent study described
      no difference in the behaviour of conventional and transformed DFSP. AIMS: To
      investigate the biological behaviour of a series of transformed DFSPs. METHODS:
      Eight transformed DFSPs were analysed clinicopathologically. Follow up ranged
      from four to 36 years. RESULTS: The tumours involved the trunk (six cases) and
      lower extremity (two cases) and measured 3.5-8 cm (median, 4). Sarcomatous change
      presented de novo in all cases. The type of sarcomatous change was FS (five
      cases) and MFH (three cases). The estimated proportion of sarcomatous area in the
      tumour was 25-70% (median, 43.37%). Mitotic counts ranged from nine to 16 mitotic
      figures/10 high power fields in the FS and MFH areas (median, 12), and from one
      to three in the DFSP areas. Six patients were treated by wide local excision with
      histopathologically negative margins and two were treated by simple surgical
      excision with positive margins. Three patients developed recurrences and one
      developed metastasis during follow up. Of those treated by wide local excision,
      one developed recurrence. All tumours expressed CD34 in the DFSP component, but
      only three in the sarcomatous area. CONCLUSIONS: Although DFSP containing sarcoma
      may be a more aggressive tumour, its behaviour can be influenced by surgical
      treatment.

PMID- 15976345
TI  - Use of native or platelet count adjusted platelet rich plasma for platelet
      aggregation measurements.
AB  - BACKGROUND: It is still not clear whether native or platelet count adjusted
      platelet rich plasma (PRP) should be used for platelet aggregation measurements.
      AIM: To evaluate the necessity of using adjusted PRP in platelet function
      testing. METHODS: Platelet aggregation with native PRP and adjusted PRP (platelet
      count: 250/nl, obtained by diluting native PRP with platelet poor plasma) was
      performed on the Behring Coagulation Timer (BCT(R)) using ADP, collagen, and
      arachidonic acid as agonists. Healthy subjects, patients on antiplatelet
      treatment, and patients with thrombocytosis (platelet counts in PRP > 1250/nl)
      were investigated. RESULTS: No significant differences in the maximum aggregation
      response were seen when using either native or adjusted PRP from healthy subjects
      and patients on antiplatelet treatment. Nevertheless, some patients taking
      aspirin or clopidogrel showed reduced inhibition of ADP and arachidonic acid
      induced aggregation in adjusted PRP but not in native PRP. The maximum velocity
      of healthy subjects and patients on antiplatelet treatment varied significantly
      as a result of the degree of dilution of the adjusted PRP. Surprisingly, the BCT
      provided good results when measuring platelet aggregation of native PRP from
      patients with thrombocytosis, whereas commonly used aggregometers could not
      analyse platelet aggregation of native PRP in these patients. CONCLUSION: The
      time consuming process of PRP adjustment may not be necessary for platelet
      aggregation measurements. Moreover, using adjusted PRP for monitoring aspirin or
      clopidogrel treatment may falsify results. Therefore, it may be better to use
      native PRP for platelet aggregation measurements, even in patients with
      thrombocytosis.

PMID- 15976347
TI  - Axillary apocrine carcinoma with benign apocrine tumours: a case report involving
      a pathological and immunohistochemical study and review of the literature.
AB  - BACKGROUND: Apocrine carcinoma is rare and often occurs in the axilla. This is
      the second apocrine carcinoma arising in bilateral axillae with associated
      apocrine hyperplasia to be reported. AIMS/METHODS: Because benign apocrine
      tumours may be precursors of cancer, this case was investigated
      immunohistochemically and histologically, and a literature (English and Japanese)
      review undertaken of cases with coexistent malignant and benign apocrine tumours
      in the axilla to elucidate the relation between apocrine carcinoma and benign
      apocrine tumours. RESULTS: Only four cases of axillary apocrine carcinoma with
      benign apocrine tumours were identified in the literature. In each case, benign
      apocrine hyperplasia was situated within and surrounding the adenocarcinomatous
      nests. Staining for epithelial membrane antigen revealed three patterns: (1)
      poorly differentiated tumour cells showing strong cytoplasmic staining; (2)
      combined luminal surface and cytoplasmic staining of glandular cells; and (3) a
      strongly positive lineal staining pattern at the luminal membrane surface,
      comprising one or two apocrine hyperplastic secretory cells. The basal lesions of
      apocrine hyperplasia were strongly positive for alpha smooth muscle actin,
      whereas the periphery of adenomatous lesions showed weaker positive staining,
      even though the periphery of adenocarcinomatous lesions was negative.
      CONCLUSIONS: All five apocrine carcinomas with benign apocrine tumours occurred
      in elderly Japanese men who had bilateral benign apocrine tumours even if
      affected by unilateral axillary apocrine carcinoma. The immunohistochemical
      results support the notion that apocrine hyperplasia is a precursor of cancer and
      that apocrine carcinoma, adenoma, and hyperplasia may be successive steps in the
      linear progression to carcinoma.

PMID- 15976348
TI  - No GIST-type c-kit gain of function mutations in neuroblastic tumours.
AB  - AIMS: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment
      in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose
      of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit
      gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset
      of tumours that would probably respond to imatinib treatment. METHODS: Expression
      of the c-kit protein was detected immunohistochemically in a total of 37 archival
      paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After
      immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of
      NT were detected with denaturing high performance liquid chromatography (HPLC).
      RESULTS: Denaturing HLPC analysis did not reveal GIST-type mutations in four
      immunohistochemically detected c-kit positive or in 33 c-kit negative NTs.
      CONCLUSIONS: c-kit receptor expression and GIST-type c-kit gene mutations are
      rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from
      that of GISTs, which may influence their responsiveness to imatinib treatment.
      Whether c-kit has an essential role in the pathogenesis of NTs remains to be
      investigated.

PMID- 15976349
TI  - Autofluorescence characterisation of isolated whole crypts and primary cultured
      human epithelial cells from normal, hyperplastic, and adenomatous colonic mucosa.
AB  - BACKGROUND/AIMS: In vivo autofluorescence endoscopic imaging and spectroscopy
      have been used to detect and differentiate benign (hyperplastic) and
      preneoplastic (adenomatous) colonic lesions. This fluorescence is composed of
      contributions from the epithelium, lamina propria, and submucosa. Because
      epithelial autofluorescence in normal and diseased tissues is poorly understood,
      this was the focus of the present study. METHODS: Whole colonic crypts were
      isolated, and short term primary cultures of epithelial cells were established
      from biopsies of normal, hyperplastic, and adenomatous colon. Autofluorescence
      (488 nm excitation) was examined by confocal fluorescence microscopy.
      Fluorescently labelled organelle probes and transmission electron microscopy were
      used to identify subcellular sources of fluorescence. RESULTS: Mitochondria and
      lysosomes were identified as the main intracellular fluorescent components in all
      cell types. Normal and hyperplastic epithelial cells were weakly autofluorescent
      and had similar numbers of mitochondria and lysosomes, whereas adenomatous
      (dysplastic) epithelial cells showed much higher autofluorescence, and numerous
      highly autofluorescent lysosomal (lipofuscin) granules. CONCLUSIONS: Short term
      primary cell cultures from endoscopic biopsies provide a novel model to
      understand differences in colonic tissue autofluorescence at the glandular
      (crypt) and cellular levels. The differences between normal, hyperplastic, and
      adenomatous epithelial cells are attributed in part to differences in the
      intrinsic numbers of mitochondria and lysosomes. This suggests that the detection
      of colonic epithelial fluorescence alone, if possible, may be sufficient to
      differentiate benign (hyperplastic) from preneoplastic and neoplastic
      (adenomatous) colonic intramucosal lesions during in vivo fluorescence endoscopy.
      Furthermore, highly orange/red autofluorescent intracellular granules found only
      in dysplastic epithelial cells may serve as a potential biomarker.

PMID- 15976350
TI  - Small cell neuroendocrine carcinoma of the breast: a report of three cases and
      review of the literature.
AB  - Small cell neuroendocrine carcinoma of the breast is a rare tumour with less than
      30 cases reported in the literature. The clinicopathological findings of three
      cases of primary neuroendocrine carcinoma of the breast and a review of the
      pertinent literature are presented. The morphological and immunohistochemical
      patterns of this tumour are similar to its pulmonary counterpart. Expression of
      neuroendocrine markers is inconsistent, so morphology is the mainstay of
      diagnosis. Size is a very important prognostic factor in this tumour, as in
      breast carcinomas of the usual type.

PMID- 15976352
TI  - Fibrocartilagenous mesenchymoma of bone: the youngest reported case in a patient
      aged 1 year and 7 months.

PMID- 15976351
TI  - Gastrointestinal stromal tumour treated with neoadjuvant imatinib.
AB  - This report describes a case of unresectable primary gastrointestinal stromal
      tumour (GIST) treated with imatinib on a neoadjuvant basis, before subsequent
      successful surgical resection. After six months of imatinib, computed tomography
      and positron emission tomography imaging demonstrated a significant size
      reduction and complete metabolic response to treatment, rendering the tumour
      resectable. Mutational analysis showed an activating KIT mutation in exon 11. The
      pathological appearance of the resected tumour was heterogeneous with extensive
      necrosis, cystic and myxoid change, extensive hypocellularity, and patchy foci of
      residual viable tumour. The implications for this management option of
      radiological, pathological, and molecular assessment are discussed.

PMID- 15976353
TI  - Large vessel arteritis: a diagnostic challenge in the elderly.

PMID- 15976354
TI  - Gamma-glutamyltransferase decreases in patients with the chronic form of
      schistosomiasis mansoni treated with ursodeoxycholic acid.

PMID- 15976355
TI  - Attenuation of skeletal muscle atrophy via protease inhibition.
AB  - Skeletal muscle atrophy in response to a number of muscle wasting conditions,
      including disuse, involves the induction of increased protein breakdown,
      decreased protein synthesis, and likely a variable component of apoptosis. The
      increased activation of specific proteases in the atrophy process presents a
      number of potential therapeutic targets to reduce muscle atrophy via protease
      inhibition. In this study, mice were provided with food supplemented with the
      Bowman-Birk inhibitor (BBI), a serine protease inhibitor known to reduce the
      proteolytic activity of a number of proteases, such as chymotrypsin, trypsin,
      elastase, cathepsin G, and chymase. Mice fed the BBI diet were suspended for 3-14
      days, and the muscle mass and function were then compared with those of the
      suspended mice on a normal diet. The results indicate that dietary
      supplementation with BBI significantly attenuates the normal loss of muscle mass
      and strength following unloading. Furthermore, the data reveal the existence of
      yet uncharacterized serine proteases that are important contributors to the
      evolution of disuse atrophy, since BBI inhibited serine protease activity that
      was elevated following hindlimb unloading and also slowed the loss of muscle
      fiber size. These results demonstrate that targeted reduction of protein
      degradation can limit the severity of muscle mass loss following hindlimb
      unloading. Thus BBI is a candidate therapeutic agent to minimize skeletal muscle
      atrophy and loss of strength associated with disuse, cachexia, sepsis,
      weightlessness, or the combination of age and inactivity.

PMID- 15976356
TI  - Exercise-induced oxidative stress leads hemolysis in sedentary but not trained
      humans.
AB  - Intravascular hemolysis is one of the most emphasized mechanisms for destruction
      of erythrocytes during and after physical activity. Exercise-induced oxidative
      stress has been proposed among the different factors for explaining exercise
      induced hemolysis. The validity of oxidative stress following exhaustive cycling
      exercise on erythrocyte damage was investigated in sedentary and trained subjects
      before and after antioxidant vitamin treatment (A, C, and E) for 2 mo. Exercise
      induced a significant increase in thiobarbituric acid-reactive substance and
      protein carbonyl content levels in sedentary subjects and resulted in an increase
      of osmotic fragility and decrease in deformability of erythrocytes, accompanied
      by signs for intravascular hemolysis (increase in plasma hemoglobin concentration
      and decrease in haptoglobulin levels). Administration of antioxidant vitamins for
      2 mo prevented exercise-induced oxidative stress (thiobarbituric acid-reactive
      substance, protein carbonyl content) and deleterious effects of exhaustive
      exercise on erythrocytes in sedentary subjects. Trained subjects' erythrocyte
      responses to exercise were different from those of sedentary subjects before
      antioxidant vitamin treatment. Osmotic fragility and deformability of
      erythrocytes, plasma hemoglobin concentration, and haptoglobulin levels were not
      changed after exercise, although the increased oxidative stress was observed in
      trained subjects. After antioxidant vitamin treatment, functional and structural
      parameters of erythrocytes were not altered in the trained group, but exercise
      induced oxidative stress was prevented. Increased percentage of young erythrocyte
      populations was determined in trained subjects by density separation of
      erythrocytes. These findings suggest that the exercise-induced oxidative stress
      may contribute to exercise-induced hemolysis in sedentary humans.

PMID- 15976357
TI  - Effects of induced hyperthyroidism in normal and cardiomyopathic hamsters.
AB  - Thyroid hormones (TH) enhance cardiac function and reverse gene changes typical
      of pathological hypertrophy. However, reports in humans, but not animals,
      indicate that excess TH can cause heart failure. Also, the effects of TH on
      normal and cardiomyopathic hearts are likely to be different. The goal of this
      study was to characterize the effects of prolonged hyperthyroidism on cardiac
      function, chamber and cellular remodeling, and protein expression in both normal
      and cardiomyopathic hearts. Hyperthyroidism was induced in 3-mo-old normal BIO
      F1B and dilated cardiomyopathic BIO TO2 hamsters. After TH treatment for 10 days
      and 2 mo, hemodynamics, echos, myocyte length, histology, and protein expression
      were assessed. After 10 days and 2 mo, there were no differences between TO2
      treated (Tx) and TO2-untreated (Untx) hamsters in chamber diameters or left
      ventricular function. After 2 mo of treatment, however, F1B-Tx showed evidence of
      dilated heart failure vs. F1B-Untx. Chamber diameters were increased, and
      ejection fraction and positive and negative changes in pressure over time were
      reduced. In F1B-Tx and TO2-Tx hamsters, beta-myosin isoform expression was
      reduced, whereas alpha-myosin increased significantly in F1B-Tx only. In TO2-Tx
      hamsters, the percent of viable myocardium was increased, and percent
      fibronecrosis was reduced vs. TO2-Untx. Myocyte length increased with TH
      treatment in both hamster strains. We conclude that 1) excess TH can induce heart
      failure in normal animals as observed in humans, 2) reversal of myosin heavy
      chain expression does not necessarily improve heart function, and 3) excess TH
      altered cellular remodeling but did not adversely affect chamber function or
      dimensions in TO2 hamsters.

PMID- 15976358
TI  - Errors of measurement for blood volume parameters: a meta-analysis.
AB  - The volume of red blood cells (V(RBC)) is used routinely in the diagnostic workup
      of polycythemia, in assessing the efficacy of erythropoietin administration, and
      to study factors affecting oxygen transport. However, errors of various methods
      of measurement of V(RBC) and related parameters are not well characterized. We
      meta-analyzed 346 estimates of error of measurement of V(RBC) for techniques
      based on Evans blue (V(RBC,Evans)), 51chromium-labeled red blood cells
      (V(RBC,51Cr)), and carbon monoxide (CO) rebreathing (V(RBC,CO)), as well as
      hemoglobin mass with the carbon-monoxide method (M(Hb,CO)), in athletes and
      active and inactive subjects undergoing various experimental and control
      treatments lasting minutes to months. Subject characteristics and experimental
      treatments had little effect on error of measurement, but measures with the
      smallest error showed some increase in error with increasing time between trials.
      Adjusted to 1 day between trials and expressed as coefficients of variation, mean
      errors for M(Hb,CO) (2.2%; 90% confidence interval 1.4-3.5%) and V(RBC,51Cr)
      (2.8%; 2.4-3.2%) were much less than those for V(RBC,Evans) (6.7%; 4.9-9.4%) and
      V(RBC,CO) (6.7%; 3.4-14%). Most of the error of V(RBC,Evans) was due to error in
      measurement of volume of plasma via Evans blue dye (6.0%; 4.5-7.8%), which is the
      basis of V(RBC,Evans). Most of the error in V(RBC,CO) was due to estimates from
      laboratories with a relatively large error in M(Hb,CO), the basis of V(RBC,CO).
      V(RBC,51Cr) and M(Hb,CO) are the best measures for research on blood-related
      changes in oxygen transport. With care, V(RBC,Evans) is suitable for clinical
      applications of blood-volume measurement.

PMID- 15976359
TI  - Effect of nasal continuous or intermittent positive airway pressure on
      nonnutritive swallowing in the newborn lamb.
AB  - The present study was aimed at investigating the effects of nasal continuous
      positive airway pressure (nCPAP; 6 cmH2O) or intermittent positive pressure
      ventilation (nIPPV; 10/4 cmH2O) on nonnutritive swallowing (NNS) and on the
      coordination between NNS and phases of the respiratory cycle, while taking into
      account the potential effects of states of alertness. Twelve full-term lambs were
      chronically instrumented at 48 h after birth for polysomnographic recordings,
      including NNS, diaphragm electromyographic activity, respiratory movements, pulse
      oximetry, and states of alertness. Studies in control conditions, with nCPAP and
      nIPPV, were performed in random order in nonsedated lambs at 4, 5, and 6 days of
      life. Results demonstrate that nCPAP significantly decreased overall NNS
      frequency, more specifically isolated NNS during quiet sleep and bursts of NNS in
      active sleep. In comparison, the effects of nIPPV on NNS frequency were more
      variable, with an inhibition of NNS only in wakefulness and an increase in
      isolated NNS frequency in active sleep. In addition, neither nCPAP nor nIPPV
      disrupted the coordination between NNS and phases of the respiratory cycle. In
      conclusion, nCPAP inhibits NNS occurrence in newborn lambs. Clinical relevance of
      this novel finding is related to the importance of NNS for clearing the upper
      airways from secretions and gastric content frequently regurgitated in the
      neonatal period.

PMID- 15976360
TI  - Fatigue and recovery of power and isometric torque following isotonic knee
      extensions.
AB  - The purpose of this study was to assess fatigue and recovery of isotonic power
      and isometric contractile properties after a series of maximal isotonic
      contractions. Using a Biodex dynamometer, 13 men [26 yr (SD 3)] performed
      isotonic [50% of isometric maximal voluntary contraction (MVC) every 1.2 s
      through 75 degrees range of motion] single-limb knee extensions at the fastest
      velocity they could achieve until velocity was reduced by 35%. Time to task
      failure was 38 s, and, compared with baseline, power declined by approximately
      42% [741.0 (SD 106.0) vs. 426.5 W (SD 60.3) at task failure], and MVC declined by
      approximately 26% [267.3 (SD 42.5) vs. 198.4 N.m (SD 45.7) at task failure].
      Power recovered by 5 min, whereas MVC did not recover, and at 10 min was only
      approximately 85% of baseline. Isometric MVC motor unit activation was
      approximately 95% at rest and was unchanged at task failure (approximately 96%),
      but a small amount of failure was apparent between 1.5 and 10 min of recovery
      (approximately 87 to approximately 91%). Half relaxation time measured from a 50
      Hz isometric tetanus was significantly prolonged by approximately 33% immediately
      after task failure but recovered by 1.5 min. A decline in the 10- to 50-Hz ratio
      of the evoked isometric contractions was observed at 5 and 10 min of recovery,
      which suggests excitation-contraction coupling impairment. Changes in velocity
      and half relaxation time during the protocol were strongly and negatively
      correlated (r = -0.85). Thus mainly peripheral mechanisms were implicated in the
      substantial depression but relatively fast recovery of isotonic power.
      Furthermore, isometric muscle contractile properties were related to some, but
      not all, changes in isotonic function.

PMID- 15976361
TI  - Fetal acidosis and hypotension during repeated umbilical cord occlusions are
      associated with enhanced chemoreflex responses in near-term fetal sheep.
AB  - This study examined the hypothesis that repeated episodes of brief but severe
      hypoxia would not attenuate the chemoreflex-mediated rapid initial fall in fetal
      heart rate (FHR) and, further, that greater hypoxic stress, as shown by
      hypotension and metabolic acidosis, would be associated with an enhanced
      chemoreflex response. Chronically instrumented, near-term fetal sheep received 1
      min total umbilical cord occlusion either every 5 min for 4 h (1:5 group; n = 8)
      or every 2.5 min (1:2.5 group; n = 8) until mean arterial blood pressure fell to
      <20 mmHg on two successive occlusions. Umbilical cord occlusion caused variable
      decelerations, with sustained hypertension in the 1:5 group and little change in
      acid-base status (pH 7.34 +/- 0.03 after 4 h). In contrast, the 1:2.5 group
      showed progressive hypotension and metabolic acidemia (pH 6.92 +/- 0.04 after the
      last occlusion). The 1:2.5 group showed a significant increase in the rate of
      initial fall in FHR during the occlusion series, which was greater than the 1:5
      group in the last 30 min of the occlusion series (9.4 +/- 1.4 vs. 3.5 +/- 0.3
      beats.min(-1).s(-1); P < 0.01), with a greater fall in FHR (71.9 +/- 6.5 vs. 47.0
      +/- 8.7 beats/min; P < 0.05). In summary, this study demonstrated that repetitive
      laborlike cord occlusions, which led to severe fetal compromise, were associated
      with an increase in the slope and magnitude of the initial FHR deceleration.
      These findings support the concept of the chemoreflex as a central, robust
      component of fetal adaptation to severe hypoxia.

PMID- 15976362
TI  - Combined pulmonary stenosis and insufficiency preserves myocardial contractility
      in the developing heart of growing swine at midterm follow-up.
AB  - This study was conducted to determine the effects of chronic combined pulmonary
      stenosis and pulmonary insufficiency (PSPI) on right (RV) and left ventricular
      (LV) function in young, growing swine. Six pigs with combined PSPI were studied,
      and data were compared with previously published data of animals with isolated
      pulmonary insufficiency and controls. Indexes of systolic function (stroke
      volume, ejection fraction, and cardiac functional reserve), myocardial
      contractility (slope of the end-systolic pressure-volume and change in pressure
      over time-end-diastolic volume relationship), and diastolic compliance were
      assessed within 2 days of intervention and 3 mo later. Magnetic resonance imaging
      was used to quantify pulmonary insufficiency and ventricular volumes. The
      conductance catheter was used to obtain indexes of the cardiac functional
      reserve, diastolic compliance, and myocardial contractility from pressure-volume
      relations acquired at rest and under dobutamine infusion. In the PSPI group, the
      pulmonary regurgitant fraction was 34.3 +/- 5.8%, the pressure gradient across
      the site of pulmonary stenosis was 20.9 +/- 20 mmHg, and the average RV peak
      systolic pressure was 70% systemic at 12 wk follow-up. Biventricular resting
      cardiac outputs and cardiac functional reserves were significantly limited (P <
      0.05), LV diastolic compliance significantly decreased (P < 0.05), but RV
      myocardial contractility significantly enhanced (P < 0.05) compared with control
      animals at 3-mo follow-up. In the young, developing heart, chronic combined PSPI
      impairs biventricular systolic pump function and diastolic compliance but
      preserves RV myocardial contractility.

PMID- 15976363
TI  - Endurance exercise training improves endothelium-dependent relaxation in brachial
      arteries from hypercholesterolemic male pigs.
AB  - We tested the hypothesis that exercise (Ex) training attenuates
      hypercholesterolemia-induced impairment of endothelium-dependent relaxation (EDR)
      in brachial (Br) arteries of adult male pigs by enhancing nitric oxide (NO)
      mediated EDR. Adult male pigs were fed a normal-fat (NF) or high-fat/cholesterol
      (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were trained
      or remained sedentary (Sed) for 16 wk, yielding four groups: 1) NF-Sed, 2) NF-Ex,
      3) HF-Sed, and 4) HF-Ex. EDR of Br artery rings was assessed in vitro with
      acetylcholine (ACh) and bradykinin (BK). ACh- and BK-induced relaxation was not
      impaired by HF; however, relaxation responses were enhanced by Ex in NF and HF
      arteries. To determine the mechanism(s) by which Ex improved EDR, ACh- and BK
      induced relaxation was assessed in the presence of N(G)-nitro-l-arginine methyl
      ester (l-NAME; to inhibit NO synthase), indomethacin (Indo; to inhibit
      cyclooxygenase), or l-NAME + Indo. ACh- and BK-induced relaxation was inhibited
      by l-NAME, and l-NAME + Indo, in all groups of arteries. Indo did not inhibit ACh
      induced relaxation in any group but did inhibit BK-induced relaxation in HF-Ex
      arteries. In the presence of l-NAME or l-NAME + Indo, ACh- and BK-induced
      relaxation in HF-Ex arteries remained greater than in HF-Sed arteries. However,
      in the presence of Indo, ACh-induced relaxation in HF-Ex arteries was no longer
      greater than in HF-Sed arteries. These results indicate that EDR is not impaired
      by hypercholesterolemia in Br arteries from adult male pigs; however, Ex improves
      EDR in HF Br arteries by enhancing production of endothelium-derived
      hyperpolarizing factor and/or prostacyclin.

PMID- 15976365
TI  - Cathodal current-induced vasodilation to single application and the amplified
      response to repeated application in humans rely on aspirin-sensitive mechanisms.
AB  - Assumed to rely on an axon reflex, the current-induced vasodilation (CIV)
      interferes with the microvascular response to iontophoretic drug delivery.
      Mechanisms resulting in CIV are likely different at the anode and at the cathode.
      While studies have been conducted to understand anodal CIV, little information is
      available on cathodal CIV. The present study investigates CIV observed following
      0.1-mA cathodal applications on forearms of healthy volunteers and the possible
      mechanisms involved. Results are expressed in percentage of the cutaneous heat
      induced maximal vascular conductance [%MVC (means +/- SE)]. 1) The amplitude of
      CIV was proportional to the duration of cathodal currents for periods of <1 min:
      r = 0.99. 2) Two current applications of 10 s, with 10-min interstimulation
      interval, induced a higher peak value of CIV (79.1 +/- 8.6% MVC) than the one
      obtained with all-at-once 20-s current application (39.5 +/- 4.3% MVC, P < 0.05).
      This amplified vascular response due to segmental application was observed for
      all tested interstimulation intervals (up to 40 min). 3) Two hours and 3 days
      following pretreatment with 1-g oral aspirin, the CIV observed following cathodal
      application, as well as the difference of cathodal CIV amplitude between all-at
      once and segmented applications, were reduced. These findings suggest a role of
      prostaglandins, not only released from endothelial or smooth muscle cells, as
      direct vasodilator and/or as a sensitizer. Thus aspirin pretreatment could be
      used to decrease CIV resulting from all-at-once and repeated cathodal application
      and facilitate the study of the specific vascular effect induced by the drug
      delivered.

PMID- 15976364
TI  - Blood pressure and hemodynamic responses to an acute sodium load in humans.
AB  - The purpose of this study was to investigate the acute blood pressure (BP) and
      hemodynamic effects of sodium chloride (3% intravenous solution). Although many
      studies link a change in dietary sodium to a change in BP, few consider the
      effects of sodium concentration in the blood on BP. We hypothesized that an
      intravenous sodium load would increase BP, and we quantified alterations in
      cardiac output (Qc) and peripheral vascular resistance (PVR). Thirteen subjects
      (age 27 +/- 2 yr) underwent a 60-min 3% saline infusion (0.15 ml.kg(-1).min(-1)).
      BP was assessed on a beat-to-beat basis with a Finometer, Qc was assessed via the
      CO(2) rebreathing technique, and PVR was derived. Serum sodium and osmolality
      increased, and hematocrit declined during the infusion (ANOVA, P < 0.01). Mean
      arterial pressure (MAP) increased continuously during the infusion from 81.8 +/-
      3.4 to 91.6 +/- 3.6 mmHg (ANOVA, P < 0.01). BP responsiveness to sodium was
      expressed as the slope of the serum sodium-MAP relationship and averaged 1.75 +/-
      0.34 mmHg.mmol(-1).l(-1). BP responsiveness to the volume change was expressed as
      the slope of the hematocrit-MAP relationship and averaged -2.2 +/- 0.35 mmHg/%.
      The early change in MAP was mediated by an increase in Qc and the late change by
      an increase in PVR (P < 0.05), corresponding to a 30% increase in plasma
      norepinephrine. In conclusion, an acute infusion of hypertonic saline was
      effective in increasing BP, and both sodium and volume appear to be involved in
      this increase; acute BP responsiveness to serum sodium can be quantified using a
      MAP-sodium plot.

PMID- 15976366
TI  - Disuse atrophy increases the muscle mechanoreflex in rats.
AB  - We investigated the effect of disuse atrophy on the magnitude of the muscle
      mechanoreflex. The left leg of eight rats (6-7 wk, male) was put in a plaster
      cast for 1 wk. The rats were decerebrated at the midcollicular level. We recorded
      the pressor and cardioaccelerator responses to 30-s stretch of the calcaneal
      tendon, which selectively stimulated the muscle mechanosensitive receptors in the
      left atrophied and right control triceps surae muscles. Atrophied muscles showed
      significantly lower mass control muscles (1.0 +/- 0.1 vs. 1.4 +/- 0.1 g; P <
      0.05). At the same stretch tension (229 +/- 20 g), the pressor response to
      stretch was significantly greater in the atrophied muscles than in the control
      muscles (13 +/- 3 vs. 4 +/- 2 mmHg, P < 0.05). The cardioaccelerator response was
      not significantly different (8 +/- 4 vs. 4 +/- 2 beats/min). Comparing responses
      at the same relative tension (57 +/- 6 vs. 51 +/- 8% of maximal tension), the
      pressor response was still significantly greater in the atrophied triceps surae
      than in the control (14 +/- 4 vs. 4 +/- 2 mmHg; P < 0.05). These results suggest
      that disuse atrophy increases the magnitude of muscle mechanoreflex.

PMID- 15976367
TI  - Adipose tissue metabolism and CD11b expression on monocytes in obese
      hypertensives.
AB  - At a given degree of adiposity, metabolic and cardiovascular risk varies markedly
      between individuals. Animal studies suggest that differentially expressed
      systemic activation of monocytes contributes to the obesity-associated risk
      variability. We tested the hypothesis that systemic monocyte activation is
      associated with changes in adipose tissue and skeletal muscle metabolism. In 17
      obese hypertensive patients, we assessed CD11b expression on circulating
      monocytes, gene expression in adipose tissue biopsies, and obtained blood samples
      and adipose tissue and skeletal muscle microdialysis samples in the fasted state
      and during a glucose load. Patients were stratified into groups with higher and
      lower CD11b expression on monocytes. Expression of the macrophage marker CD68 was
      increased markedly in adipose tissue of subjects with higher CD11b expression.
      Although no differences in systemic insulin sensitivity were found between both
      groups, patients with higher peripheral CD11b expression showed a markedly
      augmented increase in dialysate glucose in adipose tissue during oral glucose
      tolerance testing and increased adipose tissue lipolysis as well. Our data
      demonstrate that human monocyte activation is associated with tissue-specific
      changes in glucose and lipid metabolism. These findings may be explained in part
      by monocyte/macrophage infiltration of adipose tissue, which appears to interfere
      with insulin responsiveness.

PMID- 15976369
TI  - C-C chemokine receptor 5 gene variants in relation to lung disease in
      sarcoidosis.
AB  - RATIONALE: Genetic factors are likely to influence the clinical course and
      pattern of sarcoidosis, a granulomatous disease of unknown origin. OBJECTIVES: We
      tested this hypothesis for C-C chemokine receptor 5 (CCR5), a molecule involved
      in recruitment and activation of mononuclear cells. METHODS: In addition to the
      known CCR5 Delta 32 insertion/deletion, we evaluated a further eight single
      nucleotide polymorphisms in 106 British patients and 142 British unaffected
      subjects, and second-setted the results in 112 Dutch patients and 169 healthy
      Dutch control subjects. MEASUREMENTS AND MAIN RESULTS: In the British population,
      the frequency of one of the identified haplotypes (HHC) was strongly associated
      with the presence of parenchymal disease (radiographic stage >or= II versus
      stages 0 and I) at presentation (odds ratio [OR], 5.2; 95% confidence interval
      [CI], 1.96-13.7; corrected p = 0.02), at 2 (OR, 6.6; 95% CI, 2.5-17.6; corrected
      p = 0.006), and at 4 years follow-up (OR, 6.8; 95% CI, 2.5-18.0; corrected p =
      0.0045). In the Dutch population, the same association was seen at 2 (OR, 6.7;
      95% CI, 2.8-16.4; corrected p = 0.002), and 4 years follow-up (OR, 9.0; 95% CI,
      3.5-23.1; corrected p = 0.0009). CONCLUSIONS: No association between the CCR5
      haplotype HHC and susceptibility to sarcoidosis was observed, indicating that
      this relevant gene only operates after disease induction. In summary, we report a
      strong association between CCR5 haplotype HHC and persistent lung involvement in
      sarcoidosis.

PMID- 15976368
TI  - Residential proximity to naturally occurring asbestos and mesothelioma risk in
      California.
AB  - RATIONALE: Little is known about environmental exposure to low levels of
      naturally occurring asbestos (NOA) and malignant mesothelioma (MM) risk.
      OBJECTIVES: To conduct a cancer registry-based case control study of residential
      proximity to NOA with MM in California. METHODS: Incident MM cases (n = 2,908)
      aged 35 yr or more, diagnosed between 1988 and 1997, were selected from the
      California Cancer Registry and frequency matched to control subjects with
      pancreatic cancer (n = 2,908) by 5-yr age group and sex. Control subjects were
      selected by stratified random sampling from 28,123 incident pancreatic cancers in
      the same time period. We located 93.7% of subjects at the house or street level
      at initial diagnosis. Individual occupational exposure to asbestos was derived
      from the longest held occupation, available for 74% of MM cases and 63% of
      pancreatic cancers. Occupational exposure to asbestos was determined by a priori
      classification and confirmed by association with mesothelioma. MAIN RESULTS: The
      adjusted odds ratios and 95% confidence interval for low, medium, and high
      probabilities of occupational exposures to asbestos were 1.71 (1.32-2.21), 2.51
      (1.91-3.30), and 14.94 (8.37-26.67), respectively. Logistic regression analysis
      from a subset of 1,133 mesothelioma cases and 890 control subjects with
      pancreatic cancer showed that the odds of mesothelioma decreased approximately
      6.3% for every 10 km farther from the nearest asbestos source, an odds ratio of
      0.937 (95% confidence interval = 0.895-0.982), adjusted for age, sex, and
      occupational exposure to asbestos. CONCLUSIONS: These data support the hypothesis
      that residential proximity to NOA is significantly associated with increased risk
      of MM in California.

PMID- 15976370
TI  - Attenuation of bleomycin-induced pulmonary fibrosis by follistatin.
AB  - RATIONALE: Activins are members of the transforming growth factor-beta
      superfamily thought to be involved in repair processes after tissue injury.
      OBJECTIVES: The aim of this study was to clarify whether activin and its
      antagonist, follistatin, played a significant role in lung injury and fibrosis.
      METHODS AND RESULTS: In bleomycin (BLM)-treated rat lung, mRNA for the beta(A)
      subunit of activin was upregulated on Days 3 and 7 and decreased gradually
      thereafter. Immunoreactive activin A was abundantly expressed in macrophages
      infiltrated in the lung, and was detected in fibroblasts accumulated in the
      fibrotic area on Day 28. We then administered follistatin, an activin antagonist,
      to BLM-treated rats. Follistatin significantly reduced the number of macrophages
      and neutrophils in bronchoalveolar lavage and reduced the protein content.
      Histologically, follistatin markedly reduced the number of infiltrating cells,
      ameliorated the destruction of lung architecture on Day 7, and attenuated lung
      fibrosis on Day 28. The hydroxyproline content was significantly lower in
      follistatin-treated rats. In cultured lung fibroblasts, production of activin A
      was augmented by transforming growth factor-beta, and activin antagonist
      follistatin significantly inhibited transforming growth factor-beta-induced
      fibroblast activation. These results suggest that activin A was produced in the
      lung after BLM treatment and promoted acute inflammation and subsequent fibrosis.
      CONCLUSIONS: Follistatin is effective in treating acute lung injury and BLM
      induced fibrosis by blocking the actions of activin and transforming growth
      factor-beta.

PMID- 15976371
TI  - Azithromycin reverses airflow obstruction in established bronchiolitis obliterans
      syndrome.
AB  - INTRODUCTION: A recent pilot study noted clinical benefit of macrolide therapy in
      the management of six lung transplant recipients with bronchiolitis obliterans
      syndrome (BOS), a condition previously regarded as irreversible. OBJECTIVE: To
      examine the effect of low-dose macrolides on lung function in lung allograft
      recipients with established BOS and to assess whether this benefit is sustained.
      METHODS: We retrospectively evaluated the effect of azithromycin (250 mg
      alternate days) on clinical status and lung function in 20 allograft recipients
      with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent
      high-resolution computed tomography findings; and exclusion of acute rejection,
      infection, or anastomatic complications. Azithromycin was introduced at mean 82
      months after transplantation. BOS staging at initiation of treatment was BOS 3
      (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance
      immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and
      calcineurin inhibitor. RESULTS: There was a significant increase in FEV(1) of
      median 110 ml (range, -70 to 730 ml) between baseline and 3 months of
      azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months
      in the majority of patients, who had initially benefited from azithromycin (up to
      11 months follow up). CONCLUSIONS: This case series confirms the benefit of
      azithromycin in not only halting, but reversing the declining lung function seen
      in patients with BOS. This benefit appears to be maintained over time. Low-dose
      macrolides offer a new and exciting therapeutic strategy for the treatment of
      progressive BOS, and further clinical and translational mechanistic studies are
      required.

PMID- 15976372
TI  - Fractal geometry of airway remodeling in human asthma.
AB  - RATIONALE: Airway wall remodeling is an important aspect of asthma. It has proven
      difficult to assess quantitatively as it involves changes in several components
      of the airway wall. OBJECTIVE: To develop a simple method for quantifying the
      overall severity of airway wall remodeling in asthmatic airways using fractal
      geometry. METHODS: Negative-pressure silicone rubber casts of lungs were made
      using autopsy material from three groups: fatal asthma, nonfatal asthma, and
      nonasthma control. All subjects were lifelong nonsmokers. A fractal dimension was
      calculated on two-dimensional digital images of each cast. RESULTS: Nonasthma
      control casts had smooth walls and dichotomous branching patterns with
      nontapering segments. Asthmatic casts showed many abnormalities, including airway
      truncation from mucous plugs, longitudinal ridges, and horizontal corrugations
      corresponding to elastic bundles and smooth muscle hypertrophy, respectively, and
      surface projections associated with ectatic mucous gland ducts. Fractal
      dimensions were calculated from digitized images using an information method. The
      average fractal dimensions of the airways of both the fatal asthma (1.72) and
      nonfatal asthma (1.76) groups were significantly (p<0.01 and p=0.032,
      respectively) lower than that of the nonasthma control group (1.83). The lower
      fractal dimension of asthmatic airways correlated with a decreased overall
      structural complexity and pathologic severity of disease. CONCLUSION: Fractal
      analysis is a simple and useful technique for quantifying the chronic structural
      changes of airway remodeling in asthma.

PMID- 15976373
TI  - Disease-specific reference equations for lung function in patients with cystic
      fibrosis.
AB  - RATIONALE: Forced expiratory volume in one second (FEV1), an important measure of
      pulmonary disease severity in patients with cystic fibrosis (CF), is frequently
      expressed as a percentage of a predicted value derived from a healthy reference
      population. There are limitations to comparing the lung function of a patient
      with CF to that of healthy control subjects, and potential advantages to
      comparing it to that of other patients with CF. OBJECTIVE: To estimate CF
      specific percentiles of FEV1 as functions of height, age, and sex. METHODS: We
      used 287,108 FEV1 observations among more than 21,000 patients with CF in the CF
      Foundation National Patient Registry between 1994 and 2001. The percentiles were
      estimated using quantile regression methods. RESULTS: FEV1 percentile "growth
      grids" are presented, allowing comparison of an individual's FEV1 to that of
      patients with CF of the same sex, age, and height. Their potential uses in
      clinical practice and research are illustrated. CONCLUSIONS: CF-specific
      reference equations allow individual patients' FEV1 to be placed in the context
      of the distribution of lung function of their peers with CF, and should improve
      generalizability of CF clinical trials by setting entry criteria that are
      equitable across sex and age ranges. They may serve as a useful adjunct to
      conventional reference equations.

PMID- 15976374
TI  - Increased circulating endothelial progenitor cells are associated with survival
      in acute lung injury.
AB  - RATIONALE: Repair of damaged endothelium is important in recovery from acute lung
      injury. In animal models, bone marrow-derived endothelial progenitor cells
      differentiate into mature endothelium and assist in repairing damaged
      vasculature. OBJECTIVES: The quantity of endothelial progenitor cells in patients
      with acute lung injury is unknown. We hypothesize that increased numbers of
      circulating endothelial progenitor cells will be associated with an improved
      outcome in acute lung injury and the acute respiratory distress syndrome.
      METHODS: Peripheral blood mononuclear cells from the buffy coat of patients with
      early acute lung injury (n=45), intubated control subjects (n=10), and healthy
      volunteers (n=7) were isolated using Ficoll density gradient centrifugation, and
      plated on fibronectin-coated cellware. After 24 hours, nonadherent cells were
      removed and replated on fibronectin-coated cellware at a concentration of 1x10(6)
      cells/well. Colony-forming units were counted after 7 days' incubation.
      MEASUREMENTS/MAIN RESULTS: Endothelial progenitor cell colony numbers were
      significantly higher in patients with acute lung injury compared with healthy
      control subjects (p<0.05), but did not differ between patients with acute lung
      injury and intubated control subjects. However, in the 45 patients with acute
      lung injury, improved survival correlated with a higher colony count (p<0.04).
      Patients with acute lung injury with a colony count of >or= 35 had a mortality of
      30%, compared with 61% in those with colony counts <35 (p<0.03), results that
      persisted in a multivariable analysis correcting for age, sex, and severity of
      illness. CONCLUSIONS: An increased number of circulating endothelial progenitor
      cells in acute lung injury is associated with improved survival.

PMID- 15976375
TI  - Endothelial activation and increased heparan sulfate expression in cystic
      fibrosis.
AB  - RATIONALE: Pulmonary disease in cystic fibrosis (CF) is characterized by an
      exaggerated interleukin (IL)-8-driven, neutrophilic, inflammatory response to
      infection. Binding of IL-8 to heparan sulfate (HS)-containing proteoglycans
      (HSPG) facilitates binding of the chemokine to its specific receptor, stabilizes
      and prolongs IL-8 activity, and protects it from proteolysis. We hypothesized
      that increased expression of HSPG contributes to the sustained inflammatory
      response in CF bronchial tissue. OBJECTIVES: Our objectives were to analyze the
      distribution and abundance of IL-8 and HS, in intact and cleaved forms, in
      bronchial tissue from adult patients with CF or chronic obstructive pulmonary
      disease (COPD) and a control group without inflammatory airway disease. METHODS:
      Immunostaining and quantitative image analysis were applied to ethanol-fixed and
      paraffin-embedded tissue obtained at transplant in patients with CF or COPD, or
      postmortem in the control group. MEASUREMENTS AND MAIN RESULTS: Quantitative
      immunohistochemical analysis demonstrated significant disease-related
      differences. Intact HS was significantly more abundant in epithelial and
      endothelial basement membranes in CF than in COPD or the control group.
      Conversely, cleaved HS was significantly more abundant in COPD than the other
      groups. More IL-8-positive blood vessels were observed in CF and COPD compared
      with the control group, whereas more extensive IL-8 expression in the epithelium
      was observed in CF compared with COPD. CONCLUSIONS: Sustained neutrophil
      recruitment in the CF airway may therefore be related not only to increased IL-8
      expression but also to the increased stability and prolonged activity and
      retention of IL-8 when it is bound to HSPG in bronchial tissue.

PMID- 15976376
TI  - Sustained hypoxia depresses sensory processing of respiratory resistive loads.
AB  - RATIONALE: The combination of acute hypoxia and increased respiratory load is
      encountered in several respiratory diseases including acute life-threatening
      asthma and sleep apnea. Hypoxia has been shown to inhibit respiratory load
      perception in healthy and asthmatic subjects, and could contribute to treatment
      delays and impaired function of protective reflexes. OBJECTIVES: Using
      respiratory-related evoked potentials (RREPs) this study aimed to determine the
      sensory processes mediating hypoxia-induced suppression of respiratory load
      sensation. METHODS: EEG was measured over the central and parietal cortical
      regions in 14 healthy subjects. RREPs were elicited by 500-ms midinspiratory
      resistive load stimuli during and after isocapnic normoxia or hypoxia (blood
      arterial O2 saturation approximately 80%). On a separate occasion, subjects rated
      the perceived magnitude of five externally applied inspiratory resistive loads
      (range, 8.6-43.7 cm H2O x L(-1) x s) under similar experimental conditions. In
      both experiments subjects voluntarily ventilated approximately 90% above baseline
      to match ventilatory output between gas conditions. RESULTS: RREP stimulus was
      matched between gas conditions in 11 subjects (minimum mask pressure -9.7 +/- 0.6
      versus -9.2 +/- 0.4 cm H2O). P1 and P2 amplitudes were reduced during isocapnic
      hypoxia compared with normoxia (maximal at Cz: P1, 2.5 +/- 1.1 versus 3.9 +/- 1.2
      microv, p = 0.03; P2, 10.0 +/- 2.2 versus 12.4 +/- 2.1 microv, p < 0.01,
      respectively). Perceived magnitude of externally applied resistive loads was also
      reduced during hypoxia compared with normoxia (17.1 +/- 1.1 versus 19.0 +/- 1.1
      au, p < 0.01). CONCLUSIONS: These data confirm that isocapnic hypoxia suppresses
      respiratory load sensation. Decreased amplitude of the earlier (P1) RREP
      component suggests that this is mediated, at least in part, by suppression of
      respiratory afferent information before its arrival at the primary sensory
      cortex.

PMID- 15976377
TI  - Lung adenocarcinoma global profiling identifies type II transforming growth
      factor-beta receptor as a repressor of invasiveness.
AB  - RATIONALE: Lung adenocarcinoma histology and clinical outcome are heterogeneous
      and associated with tumor invasiveness. OBJECTIVES: We hypothesized that
      invasiveness is associated with a distinct molecular signature and that genes
      differentially expressed in tumor or adjacent stroma will identify cell surface
      signal transduction and matrix remodeling pathways associated with the
      acquisition of invasiveness in lung adenocarcinoma. MAIN RESULTS: Microarray
      analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and
      invasive adenocarcinoma and adenocarcinoma-mixed type with BAC features
      identified transcriptional profiles of lung adenocarcinoma invasiveness. Among
      the signature set that was lower in adenocarcinoma-mixed compared with BAC was
      the type II transforming growth factor beta (TGF-beta) receptor, suggesting
      downregulation of TGFbetaRII is an early event in lung adenocarcinoma metastasis.
      Immunostaining in independently acquired specimens demonstrated a correlation
      between TbetaRII expression and length of tumor invasion. Repression of
      TGFbetaRII in lung cancer cells increased tumor cell invasiveness and activated
      p38 mitogen-activated protein kinases. Microarray analysis of invasive cells
      identified potential downstream mediators of TGFbetaRII with differential
      expression in lung adenocarcinomas. CONCLUSIONS: The repression of type II TGF
      beta receptor may act as a significant determinant of lung adenocarcinoma
      invasiveness, an early step in tumor progression toward metastasis.

PMID- 15976378
TI  - Oxidative stress and left ventricular function with chronic intermittent hypoxia
      in rats.
AB  - RATIONALE AND OBJECTIVES: Obstructive sleep apnea (OSA) is associated with
      oxidative stress and myocardial dysfunction. We hypothesized that the chronic
      intermittent hypoxia (CIH) component of OSA is sufficient to lead to these
      adverse effects. METHODS AND RESULTS: Rats were exposed to CIH (nadir O2, 4-5%)
      for 8 hours/day, 5 days/week, for 5 weeks. Results were compared with similarly
      handled controls (HC). Outcomes included blood pressure (tail cuff
      plethysmograph), echocardiographic and invasive measures of left-ventricular (LV)
      function, and indices of oxidative stress that included levels of myocardial
      lipid peroxides and Cu/Zn superoxide dismutase. Blood pressure was greater in CIH
      (n=22) than in HC (n=22) after 2 weeks of exposure (136+/-12 vs. 128+/-8 mm Hg;
      p<0.05). However, the difference disappeared by 5 weeks (127+/-13 vs. 127+/-13 mm
      Hg). LV weight/heart weight was greater with CIH (CIH, 0.52+/-0.05; HC, 0.47+/
      0.06; p<0.005). Echocardiograms revealed LV dilation, as well as decreased LV
      fractional shortening (CIH, 29.7+/-9.8%; HC, 37.4+/-7.1%; p<0.001). LV end
      diastolic pressure was increased with CIH (CIH, 13.7+/-5.5; HC, 8.0+/-2.9 mm Hg;
      p<0.001), decreased LV dp/dtmax (CIH, 5072+/-2191; HC, 6596+/-720 mm Hg/second;
      p<0.039), and decreased cardiac output (CIH, 48.2+/-10.5; HC, 64.1+/-10.9
      ml/minute; p<0.001). LV myocardial lipid peroxides were greater (CIH, 1,258+/
      703; HC 715+/-240 microm/mg protein; p<0.05) and LV myocardial superoxide
      dismutase levels were lower (CIH, 10.3+/-4.9; HC, 18.6+/-8.2 U/mg protein;
      p<0.05) with CIH. CONCLUSIONS: CIH leads to oxidative stress and LV myocardial
      dysfunction.

PMID- 15976379
TI  - ABCA3 mutations associated with pediatric interstitial lung disease.
AB  - RATIONALE: ABCA3 is a member of the ATP-binding cassette family of proteins that
      mediate the translocation of a wide variety of substrates, including lipids,
      across cellular membranes. Mutations in the gene encoding ABCA3 were recently
      identified in full-term neonates with fatal surfactant deficiency. OBJECTIVE: To
      test the hypothesis that ABCA3 mutations are not always associated with fatal
      neonatal lung disease but are a cause of pediatric interstitial lung disease.
      METHODS: DNA samples were obtained from 195 children with chronic lung disease of
      unknown etiology. The 30 coding exons of the ABCA3 gene were sequenced in four
      unrelated children with a referring diagnosis of desquamative interstitial
      pneumonitis and who were older than 10 years at the time of enrollment. RESULTS:
      Three of four patients (ages 16, 23, and 11 years) with desquamative interstitial
      pneumonitis had ABCA3 mutations identified on both alleles. All three had the
      same missense mutation (E292V) and a second unique mutation. The E292V mutation
      was not found on 200 control alleles from adults without lung disease, but seven
      additional patients of the remaining study patients had the E292V mutation on one
      allele. Immunohistochemical analysis of surfactant protein expression in three
      patients revealed a specific staining pattern for surfactant protein-B, which was
      the same pattern observed in several infants with fatal lung disease due to ABCA3
      mutations. CONCLUSION: ABCA3 mutations cause some types of interstitial lung
      disease in pediatric patients.

PMID- 15976380
TI  - Titrating steroids on exhaled nitric oxide in children with asthma: a randomized
      controlled trial.
AB  - RATIONALE: Corticosteroids are the antiinflammatory treatment of choice in
      asthma. Treatment guidelines are mainly symptom-driven but symptoms are not
      closely related to airway inflammation. The fraction of nitric oxide in exhaled
      air (FENO) is a marker of airway inflammation in asthma. OBJECTIVE: We evaluated
      whether titrating steroids on FENO improved asthma management in children.
      METHODS: Eighty-five children with atopic asthma, using inhaled steroids, were
      allocated to a FENO group (n=39) in which treatment decisions were made on both
      FENO and symptoms, or to a symptom group (n=46) treated on symptoms only.
      Children were seen every 3 months over a 1-year period. MEASUREMENTS: Symptoms
      were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO
      was measured at all visits, and airway hyperresponsiveness and FEV1 were measured
      at the start and end of the study. Primary endpoint was cumulative steroid dose.
      RESULTS: Changes in steroid dose from baseline did not differ between groups. In
      the FENO group, hyperresponsiveness improved more than in the symptom group (2.5
      vs. 1.1 doubling dose, p=0.04). FEV1 in the FENO group improved, and the change
      in FEV1 was not significantly different between groups. The FENO group had 8
      severe exacerbations versus 18 in the symptom group. The change in symptom scores
      did not differ between groups. FENO increased in the symptom group; the change in
      FENO from baseline differed between groups (p=0.02). CONCLUSION: In children with
      asthma, 1 year of steroid titration on FENO did not result in higher steroid
      doses and did improve airway hyperresponsiveness and inflammation.

PMID- 15976382
TI  - Prevalence of chronic obstructive pulmonary disease in Korea: a population-based
      spirometry survey.
AB  - RATIONALE: Although chronic obstructive pulmonary disease is a leading cause of
      mortality and morbidity worldwide, there are only limited data on its prevalence,
      especially in Asia. OBJECTIVES: A population-based epidemiologic survey of
      chronic obstructive pulmonary disease in a representative national sample was
      conducted using spirometry. METHODS: A stratified multistage clustered
      probability design was used to select a nationally representative sample. The
      survey was performed in conjunction with the second Korean National Health and
      Nutrition Examination Survey of 9,243 adults over the age of 18 years. The
      participation rate was 88.8% for questionnaires and 52.1% for spirometry.
      RESULTS: The prevalence of chronic obstructive pulmonary disease based on Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (a ratio of FEV1
      to FVC of less than 0.7) was 17.2% (men, 25.8%; women, 9.6%) among subjects older
      than 45 years. Among adults of all ages (age>18 years), the prevalence of airflow
      obstruction was 7.8% (10.9% in men, 4.9% in women). The majority of these cases
      were found to be mild in degree, and only a minority of these subjects had
      received physician diagnosis or treatment. Multivariate analysis revealed that
      age over 65 years, male sex, smoking more than 20 pack-years, and low income were
      independent predictors for chronic obstructive pulmonary disease. CONCLUSIONS:
      Seventeen percent of Korean adults over the age of 45 years have mild chronic
      obstructive pulmonary disease.

PMID- 15976381
TI  - Inhaled nitric oxide effects on lung structure and function in chronically
      ventilated preterm lambs.
AB  - RATIONALE: Inhaled nitric oxide (iNO) can reverse neonatal pulmonary hypertension
      and bronchoconstriction and reduce proliferation of cultured arterial and airway
      smooth muscle cells. OBJECTIVES: To see if continuous iNO from birth might reduce
      pulmonary vascular and respiratory tract resistance (PVR, RE) and attenuate
      growth of arterial and airway smooth muscle in preterm lambs with chronic lung
      disease. METHODS: Eight premature lambs received mechanical ventilation for 3
      weeks, four with and four without iNO (5-15 ppm). Four term lambs, mechanically
      ventilated without iNO for 3 weeks, served as additional control animals.
      MEASUREMENTS: PVR and RE were measured weekly. After 3 weeks, lung tissue was
      processed for quantitative image analysis of smooth muscle abundance around small
      arteries (SMart) and terminal bronchioles (SMtb). Radial alveolar counts were
      done to assess alveolar number. Endothelial NO synthase (eNOS) protein in
      arteries and airways was measured by immunoblot analysis. MAIN RESULTS: At
      study's end, PVR was similar in iNO-treated and untreated preterm lambs; PVR was
      less in iNO-treated preterm lambs compared with term control animals. RE in iNO
      treated lambs was less than 40% of RE measured in preterm control animals. SMart
      was similar in iNO-treated and both groups of control lambs; SMtb in lambs given
      iNO was significantly less (approximately 50%) than in preterm control animals.
      Radial alveolar counts of iNO-treated lambs were more than twice that of preterm
      control animals. eNOS was similar in arteries and airways of iNO-treated preterm
      lambs compared with control term lambs. CONCLUSIONS: iNO preserves structure and
      function of airway smooth muscle and enhances alveolar development in preterm
      lambs with chronic lung disease.

PMID- 15976383
TI  - Extended haplotype in the tumor necrosis factor gene cluster is associated with
      asthma and asthma-related phenotypes.
AB  - RATIONALE: Tumor necrosis factor is a proinflammatory cytokine found in increased
      concentrations in asthmatic airways. The TNF-alpha (TNF) and lymphotoxin-alpha
      (LTA) genes belong to the TNF gene superfamily located within the human major
      histocompatibility complex on chromosome 6p in a region repeatedly linked to
      asthma. The TNF position -308 and LTA NcoI polymorphisms are believed to
      influence TNF transcription and secretion, respectively. OBJECTIVES: This study
      sought to determine whether polymorphisms in TNF or LTA, or in TNF-LTA
      haplotypes, are associated with asthma and asthma phenotypes. METHODS: We
      genotyped the TNF -308 and LTA NcoI polymorphisms, and two other haplotype
      tagging polymorphisms in the TNF and LTA genes, in 708 children with mild to
      moderate asthma enrolled in the Childhood Asthma Management Program and in their
      parents. Using an extension of the family-based association tests in the PBAT
      program, each polymorphism was tested for association with asthma, age at onset
      of asthma, and time series data on baseline FEV(1) % predicted,
      postbronchodilator FEV(1) % predicted, body mass index, and log of PC(20).
      MEASUREMENTS AND MAIN RESULTS: Although no associations were found for the
      individual single-nucleotide polymorphisms, the haplotype analysis found the LTA
      NcoI_G/LTA 4371T/TNF -308G/TNF 1078G haplotype to be associated with asthma and
      with all five phenotype groups. CONCLUSIONS: We conclude that it is unlikely that
      the TNF -308 or LTA NcoI polymorphisms influence asthma susceptibility
      individually, but that this haplotype of variants may be functional or may be in
      linkage disequilibrium with other functional single-nucleotide polymorphisms.

PMID- 15976384
TI  - Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients
      with asthma.
AB  - RATIONALE: Genetic variation of the beta2-adrenoceptor (ADRB2) influences
      receptor function in vitro. There are reports that, in vivo, bronchodilator
      response is related to ADRB2 genotype, and that clinical outcomes during chronic
      therapy with beta2-agonist drugs are also influenced by genotype. Whether these
      features are related to single nucleotide polymorphisms or to combinations
      (haplotypes) is unclear. OBJECTIVES: Our aim was to measure bronchodilator
      response in patients with asthma stratified by ADRB2 haplotype. This was done
      after eliminating the confounding effect of prior drug treatment with inhaled
      beta2-agonists and corticosteroids. METHODS: ADRB2 haplotype was determined in
      176 patients with asthma, of whom 161 harbored the six most common combinations.
      Treatment with inhaled beta2-agonists and inhaled corticosteroids was withheld
      for appropriate intervals. Spirometric changes 20 minutes after a single dose of
      albuterol (2.5 mg by nebulizer) were then recorded. RESULTS: There were no
      significant differences in bronchodilator response (% improvement in FEV(1)) with
      respect to any of the major ADRB2 haplotypes or genotypes. CONCLUSIONS: Genetic
      variation of the ADRB2 does not influence the immediate response to inhaled beta2
      agonist. The confounding effect of tolerance resulting from regular beta2-agonist
      use must be controlled when assessing the pharmacogenetic influences on clinical
      outcomes with beta2-agonists.

PMID- 15976385
TI  - Metabolic adaptations of liver mitochondria during restricted feeding schedules.
AB  - Food anticipatory activity (FAA) is an output of the food-entrained oscillator
      (FEO), a conspicuous biological clock that expresses when experimental animals
      are under a restricted food schedule (RFS). We have shown that the liver is
      entrained by RFS and exhibits an anticipatory response before meal time in its
      oxidative and energetic state. The present study was designed to determine the
      mitochondrial oxidative and phosphorylating capacity in the liver of rats under
      RFS to further support the biochemical anticipatory role that this organ plays
      during the food entrainment (9). Metabolic and functional parameters of liver
      mitochondria were characterized before (0800 h), during (1100 h), and after (1400
      h) FAA. The main results were as follows. First, there was an enhancement during
      FAA (1100 h) in 1) oxidative capacity (site I of the electron transport chain),
      2) phosphorylating ability (estimated by ATP synthesis), and 3) activities of
      NADH shuttles. Second, after rats were fed (1400 h), the phosphorylating capacity
      remained high, but this was not the case for the respiratory control ratio for
      site I. Finally, in the three experimental conditions before, during, and after
      FAA, an increment was detected in the H(+) electrochemical potential, due to an
      elevation in mitochondrial membrane potential, and in mitochondrial yield. Most
      of the changes in mitochondrial properties related to RFS were also present when
      results were compared with those from the 24-h fasted group. In conclusion, the
      results support the notion that a distinctive rheostatic state is installed in
      the metabolic activity of the liver when FEO is being expressed.

PMID- 15976386
TI  - Calcium dependence of proteinase-activated receptor 2 and cholecystokinin
      mediated amylase secretion from pancreatic acini.
AB  - Pancreatic acini secrete digestive enzymes in response to a variety of
      secretagogues including CCK and agonists acting via proteinase-activated receptor
      2 (PAR2). We employed the CCK analog caerulein and the PAR2-activating peptide
      SLIGRL-NH(2) to compare and contrast Ca(2+) changes and amylase secretion
      triggered by CCK receptor and PAR2 stimulation. We found that secretion
      stimulated by both agonists is dependent on a rise in cytoplasmic Ca(2+)
      concentration ([Ca(2+)](i)) and that this rise in [Ca(2+)](i) reflects both the
      release of Ca(2+) from intracellular stores and accelerated Ca(2+) influx. Both
      agonists, at low concentrations, elicit oscillatory [Ca(2+)](i) changes, and both
      trigger a peak plateau [Ca(2+)](i) change at high concentrations. Although the
      two agonists elicit similar rates of amylase secretion, the rise in [Ca(2+)](i)
      elicited by caerulein is greater than that elicited by SLIGRL-NH(2). In Ca(2+)
      free medium, the rise in [Ca(2+)](i) elicited by SLIGRL-NH(2) is prevented by the
      prior addition of a supramaximally stimulating concentration of caerulein, but
      the reverse is not true; the rise elicited by caerulein is neither prevented nor
      reduced by prior addition of SLIGRL-NH(2). Both the oscillatory and the peak
      plateau [Ca(2+)](i) changes that follow PAR2 stimulation are prevented by the
      phospholipase C (PLC) inhibitor U73122, but U73122 prevents only the oscillatory
      [Ca(2+)](i) changes triggered by caerulein. We conclude that 1) both PAR2 and CCK
      stimulation trigger amylase secretion that is dependent on a rise in [Ca(2+)](i)
      and that [Ca(2+)](i) rise reflects release of calcium from intracellular stores
      as well as accelerated influx of extracellular calcium; 2) PLC mediates both the
      oscillatory and the peak plateau rise in [Ca(2+)](i) elicited by PAR2 but only
      the oscillatory rise in [Ca(2+)](i) elicited by CCK stimulation; and 3) the rate
      of amylase secretion elicited by agonists acting via different types of receptors
      may not correlate with the magnitude of the [Ca(2+)](i) rise triggered by those
      different types of secretagogue.

PMID- 15976387
TI  - Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial
      cells.
AB  - This study was undertaken to determine whether the Bcl-2 family proteins and Smac
      are regulators of aspirin-mediated apoptosis in a gastric mucosal cell line known
      as AGS cells. Cells were incubated with varying concentrations of acetylsalicylic
      acid (ASA; 2-40 mM), with or without preincubation of caspase inhibitors.
      Apoptosis was characterized by Hoechst staining and DNA-histone-associated
      complex formation. Antiapoptotic Bcl-2, proapoptotic Bax and Bid, Smac, and
      cytochrome-c oxidase (COX IV) were analyzed by Western blot analyses from cytosol
      and mitochondrial fractions. ASA downregulated Bcl-2 protein expression and
      induced Bax translocation into the mitochondria and cleavage of Bid. In contrast,
      expression of Smac was significantly decreased in mitochondrial fractions of ASA
      treated cells. Bax and Bid involvement in apoptosis regulation was dependent on
      caspase activation, because caspase-8 inhibition suppressed Bax translocation and
      Bid processing. Caspase-9 inhibition prevented Smac release from mitochondria.
      Additionally, increased expression of the oxidative phosphorylation enzyme COX IV
      was observed in mitochondrial fractions exposed to ASA at concentrations >5 mM.
      Although caspase-8 inhibition had no effect on aspirin-induced apoptosis and DNA
      histone complex formation, caspase-9 inhibition significantly decreased both of
      these events. We conclude that Bcl-2 protein family members and Smac regulate the
      apoptotic pathway in a caspase-dependent manner. Our results indicate also that
      mitochondrial integration and oxidative phosphorylation play a critical role in
      the pathogenesis of apoptosis in human gastric epithelial cells.

PMID- 15976388
TI  - Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT
      lymphocytes.
AB  - Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage.
      Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to
      determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in
      groups A and B were treated with GC 2 h before and 2 h following administration
      of ConA, respectively; group C mice were treated with ConA; group D mice was
      treated with GC; group E mice did not receive any treatment. Liver damage was
      evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT) levels and liver histology. The immune effect of GC was determined by
      fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT
      lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT
      1, 4, 6, and NF-kappaB expression. The effect of GC on NKT cell proliferation was
      assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated
      group A mice compared with nontreated group C animals, and histological damage
      was markedly attenuated in group A. The beneficial effect of GC was associated
      with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of
      serum IFN-gamma levels, and decreased STAT1 and STAT6 expression. In vitro
      administration of GC led to a 42% decrease of NKT cell proliferation in the
      presence of dendritic cells but not in their absence. Intraperitoneally
      administered radioactive GC was detected in the liver and bowel. Administration
      of GC led to amelioration of ConA hepatitis associated with an inhibitory effect
      on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.

PMID- 15976389
TI  - Pancreatic response to endotoxin after chronic alcohol exposure: switch from
      apoptosis to necrosis?
AB  - Chronic alcohol consumption is known to increase the susceptibility to acute and
      chronic pancreatitis, and it is likely that a cofactor is required to initiate
      the progression to alcoholic pancreatitis. The severity and complications of
      alcoholic and nonalcoholic acute pancreatitis may be influenced by a number of
      cofactors, including endotoxemia. To explore the effect of a possible cofactor,
      we used endotoxin [lipopolysaccharide (LPS)] as a tool to induce cellular injury
      in the alcoholic pancreas. Single, increasing doses of endotoxin were injected in
      rats fed an alcohol or control diet and killed 24 h after the injection. We
      examined the mechanism by which LPS exacerbates pancreatic injury in alcohol-fed
      rats and whether the injury is associated with apoptosis or necrosis. We showed
      that chronic alcohol exposure alone inhibits apoptosis through the intrinsic
      pathway and the downstream apoptosis executor caspase-3 compared with the
      controls. Pancreatic necrosis and inflammation increased after LPS injection in
      control and alcohol-fed rats in a dose-dependent fashion but with a significantly
      greater response in the alcohol-fed animals. Caspase activities and TdT-mediated
      dUTP nick-end labeling positivity were lower in the alcoholic pancreas injected
      with LPS, whereas the histopathology and inflammation were more severe compared
      with the control-fed animals. Assessment of a putative indicator of necrosis, the
      ratio of ADP to ATP, indicated that alcohol exposure accelerates pancreatic
      necrosis in response to endotoxin. These findings suggest that the pancreas
      exposed to alcohol is more sensitive to LPS-induced damage because of increased
      sensitivity to necrotic cell death rather than apoptotic cell death. Similar to
      the liver, the pancreas is capable of responding to LPS with a more severe
      response in alcohol-fed animals, favoring pancreatic necrosis rather than
      apoptosis. We speculate that this mechanism may occur in acute alcoholic
      pancreatitis patients.

PMID- 15976390
TI  - Sensory peptide neurotransmitters mediating mucosal and distension evoked neural
      vasodilator reflexes in guinea pig ileum.
AB  - The aim was to determine the role CGRP and/or tachykinins released from sensory
      neural mechanisms in enteric neural vasodilator pathways. These pathways project
      through the myenteric plexus to submucosal vasodilator neurons. Submucosal
      arterioles were exposed in the distal portion of an in vitro combined submucosal
      myenteric guinea pig ileal preparation, and dilation was monitored with
      videomicroscopy. Vasodilator neural reflexes were activated by gently stroking
      the mucosa with a fine brush or by distending a balloon placed beneath the flat
      sheet preparation in the proximal portion. Dilations evoked by mucosal stroking
      were inhibited 64% by the CGRP 8-37 and 37% by NK3 (SR 142801) antagonists. When
      the two antagonists were combined with hexamethonium, only a small vasodilation
      persisted. Balloon distension-evoked vasodilations were inhibited by NK3
      antagonists (66%) but were not altered by CGRP 8-37. In preparations in which
      myenteric descending interneurons were directly activated by electrical
      stimulation, combined application of CGRP 8-37 and the NK antagonists had no
      effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not
      activate these vasodilator reflexes. These findings suggest that mucosal
      activated reflexes result from the release of CGRP and tachykinins from enteric
      sensory neurons. Distension-evoked responses were significantly blocked by NK3
      antagonists, suggesting that stretch activation of myenteric sensory neurons
      release tachykinins that activate NK3 receptors on myenteric vasodilator
      pathways.

PMID- 15976391
TI  - Zinc finger transcription factor Egr-1 is involved in stimulation of NHE2 gene
      expression by phorbol 12-myristate 13-acetate.
AB  - The apical membrane Na(+)/H(+) exchanger isoforms NHE2 and NHE3 are involved in
      transepithelial Na(+) absorption in the intestine. However, they exhibit
      differences in their pattern of tissue expression and regulation of their
      activity by various molecular signals. To study the mechanisms involved in the
      transcriptional regulation of these genes, we characterized cis-acting elements
      within the human NHE2 promoter that regulate NHE2 promoter expression in C2BBe1
      cells. A small DNA region (-85/+249) was involved in the regulation of basal
      transcriptional activity of the NHE2 promoter as determined by transient
      transfection assays. RT-PCR analysis showed that NHE2 mRNA was upregulated in
      response to phorbol 12-myristate 13-acetate (PMA). Results from actinomycin D
      treated cells indicated that the regulation of the NHE2 gene by PMA occurs in
      part at the transcriptional level. Furthermore, PMA treatment led to a 100%
      increase in promoter activity through elements located on the -415/+249 DNA
      fragment. A PMA-induced nuclear factor that bound to the NHE2 promoter was
      identified as the transcription factor Egr-1. We identified two PMA response
      elements in the -415/+1 promoter region that bind to Sp1 and Sp3 in untreated
      nuclear extracts and to Egr-1 in PMA-treated nuclear extracts. In cotransfection
      experiments, Egr-1 was able to transactivate the NHE2 promoter. Our data indicate
      that Egr-1 may play a key role in regulated expression of the human NHE2 gene.

PMID- 15976392
TI  - Inhaled iloprost in pulmonary arterial hypertension.
AB  - OBJECTIVE: To review the pharmacology, pharmacodynamics, and clinical trials
      evaluating inhaled iloprost in pulmonary arterial hypertension (PAH). DATA
      SOURCES: A MEDLINE search (1996-February 2005) was performed using the key words
      pulmonary hypertension, iloprost, and epoprostenol. Information regarding Food
      and Drug Administration approval was obtained via the Internet. STUDY SELECTION
      AND DATA EXTRACTION: All clinical trials using inhaled iloprost in PAH published
      in English were identified. Additionally, references from the identified articles
      were reviewed. DATA SYNTHESIS: A stable analog of prostacyclin, inhaled iloprost
      is thought to promote benefit in PAH through vasodilation, antiproliferative
      effects, and inhibition of platelet aggregation. In a placebo-controlled trial of
      203 patients, inhaled iloprost significantly improved the combined endpoint of
      change in New York Heart Association functional class and 10% improvement in 6
      minute walk distance (p = 0.007). Small, short-term clinical trials demonstrated
      hemodynamic benefits for inhaled iloprost alone and in combination with other
      pulmonary vasodilating agents. The aerosolized delivery route and low incidence
      of adverse events are positive attributes for inhaled iloprost, while the
      frequency of administration and lack of comparative data limit its role in PAH.
      CONCLUSIONS: Currently, inhaled iloprost offers potential benefit for patients
      with contraindications to bosentan, preference for non-parenteral products,
      ineligibility for parenteral therapy, or as adjunctive therapy with other
      pulmonary vasodilators. Larger, long-term clinical trials are needed to solidify
      the role for inhaled iloprost in the management of PAH.

PMID- 15976393
TI  - Hysterectomy for benign conditions.

PMID- 15976394
TI  - Where next with revalidation?

PMID- 15976395
TI  - Health research policy in the European Union.

PMID- 15976396
TI  - The future of singlehanded general practices.

PMID- 15976397
TI  - Thresholds for normal blood pressure and serum cholesterol.

PMID- 15976398
TI  - Court hears shaken baby cases.

PMID- 15976399
TI  - GMC hears case against paediatrician in Sally Clark trial.

PMID- 15976400
TI  - Little progress has been made in combating hospital infections.

PMID- 15976401
TI  - Alder Hey pathologist is struck off medical register.

PMID- 15976403
TI  - National nutrition council is needed to tackle childhood obesity.

PMID- 15976404
TI  - Approval of FDA commissioner held up by emergency contraception issue.

PMID- 15976407
TI  - Conduct of drug trials in poor countries must improve.

PMID- 15976408
TI  - BMA calls on G8 governments to address "brain drain".

PMID- 15976405
TI  - 10m pounds sterling settlement for children misdiagnosed with epilepsy.

PMID- 15976409
TI  - "Super surgeries" threaten general practice.

PMID- 15976410
TI  - US stem cell research progresses despite limitations.

PMID- 15976411
TI  - Autopsy supports claim that Schiavo was in a persistent vegetative state.

PMID- 15976412
TI  - Doctors and company to be held liable for contraceptive failure.

PMID- 15976413
TI  - Heart attack care is improving in England and Wales.

PMID- 15976414
TI  - US government cuts penalty on tobacco firms as racketeering case closes.

PMID- 15976416
TI  - Extradition bid is likely after findings against doctor.

PMID- 15976417
TI  - Indian government bans smoking in new films and TV serials.

PMID- 15976418
TI  - UK stops short of outright smoking ban in enclosed public places.

PMID- 15976419
TI  - Evacuation decisions in a chemical air pollution incident: cross sectional
      survey.
AB  - OBJECTIVE: To compare the health outcomes in sheltered and evacuated populations
      after a chemical incident in a plastics factory. DESIGN: Cross sectional survey.
      SETTING: Urban area in southwest England. PARTICIPANTS: 1750 residents from the
      area exposed to the chemical smoke, of which 472 were evacuated and the remaining
      1278 were advised to shelter indoors. MAIN OUTCOME MEASURE: Number of adverse
      health symptoms. A case was defined by the presence of four or more symptoms.
      MAIN RESULTS: 1096 residents (63%; 299 evacuated, 797 sheltered) provided data
      for analyses. The mean symptom score and proportion of cases were higher in
      evacuated people than in the sheltered population (evacuated: symptom score 1.9,
      cases 19.7% (n = 59); sheltered: symptom score 1.0, cases 9.5% (n = 76); P <
      0.001 for both). The difference between the two groups attenuated markedly at the
      end of two weeks from the start of the incident. The two main modifiable risk
      factors for the odds of becoming a case were evacuation (odds ratio 2.5, 95%
      confidence interval 1.7 to 3.8) and direct exposure to smoke for more than two
      hours on the first day of the incident (2.0, 1.7 to 2.3). The distance of
      residence from the factory or level of exposure before intervention (first six
      hours) had little effect on the odds of a person becoming a case. CONCLUSIONS:
      Sheltering may have been a better protective action than evacuation in this
      chemical incident, which is consistent with the prevailing expert view. Although
      this study has limitations, it is based on a real event. Evacuations carry their
      own risks and resource implications; increased awareness may help to reduce
      unnecessary evacuations in the future.

PMID- 15976420
TI  - Evacuation decisions in chemical incidents benefit from expert health advice.

PMID- 15976421
TI  - The role of healthcare delivery in the outcome of meningococcal disease in
      children: case-control study of fatal and non-fatal cases.
AB  - OBJECTIVE: To determine whether suboptimal management in hospital could
      contribute to poor outcome in children admitted with meningococcal disease.
      DESIGN: Case-control study of childhood deaths from meningococcal disease,
      comparing hospital care in fatal and non-fatal cases. SETTING: National
      statistics and hospital records. SUBJECTS: All children under 17 years who died
      from meningococcal disease (cases) matched by age with three survivors (controls)
      from the same region of the country. MAIN OUTCOME MEASURES: Predefined criteria
      defined optimal management. A panel of paediatricians blinded to the outcome
      assessed case records using a standardised form and scored patients for
      suboptimal management. RESULTS: We identified 143 cases and 355 controls.
      Departures from optimal (per protocol) management occurred more frequently in the
      fatal cases than in the survivors. Multivariate analysis identified three factors
      independently associated with an increased risk of death: failure to be looked
      after by a paediatrician, failure of sufficient supervision of junior staff, and
      failure of staff to administer adequate inotropes. Failure to recognise
      complications of the disease was a significant risk factor for death, although
      not independently of absence of paediatric care (P = 0.002). The odds ratio for
      death was 8.7 (95% confidence interval 2.3 to 33) with two failures, increasing
      with multiple failures. CONCLUSIONS: Suboptimal healthcare delivery significantly
      reduces the likelihood of survival in children with meningococcal disease.
      Improved training of medical and nursing staff, adherence to published protocols,
      and increased supervision by consultants may improve the outcome for these
      children and also those with other life threatening illnesses.

PMID- 15976422
TI  - Methods of hysterectomy: systematic review and meta-analysis of randomised
      controlled trials.
AB  - OBJECTIVE: To evaluate the most appropriate surgical method of hysterectomy
      (abdominal, vaginal, or laparoscopic) for women with benign disease. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: Cochrane Menstrual Disorders
      and Subfertility Group Trials Register, Cochrane Central Register of Controlled
      Trials, Medline, Embase, and Biological Abstracts. SELECTION OF STUDIES: Only
      randomised controlled trials were selected; participants had to have benign
      gynaecological disease; interventions had to comprise at least one hysterectomy
      method compared with another; and trials had to report primary outcomes (time
      taken to return to normal activities, intraoperative visceral injury, and major
      long term complications) or secondary outcomes (operating time, other immediate
      complications of surgery, short term complications, and duration of hospital
      stay). RESULTS: 27 trials (total of 3643 participants) were included. Return to
      normal activities was quicker after vaginal than after abdominal hysterectomy
      (weighted mean difference 9.5 (95% confidence interval 6.4 to 12.6) days) and
      after laparoscopic than after abdominal hysterectomy (difference 13.6 (11.8 to
      15.4) days), but was not significantly different for laparoscopic versus vaginal
      hysterectomy (difference -1.1 (-4.2 to 2.1) days). There were more urinary tract
      injuries with laparoscopic than with abdominal hysterectomy (odds ratio 2.61 (95%
      confidence interval 1.22 to 5.60)), but no other intraoperative visceral injuries
      showed a significant difference between surgical approaches. Data were notably
      absent for many important long term patient outcome measures, where the analyses
      were underpowered to detect important differences, or they were simply not
      reported in trials. CONCLUSIONS: Significantly speedier return to normal
      activities and other improved secondary outcomes (shorter duration of hospital
      stay and fewer unspecified infections or febrile episodes) suggest that vaginal
      hysterectomy is preferable to abdominal hysterectomy where possible. Where
      vaginal hysterectomy is not possible, laparoscopic hysterectomy is preferable to
      abdominal hysterectomy, although it brings a higher chance of bladder or ureter
      injury.

PMID- 15976423
TI  - Creative use of existing clinical and health outcomes data to assess NHS
      performance in England: part 2--more challenging aspects of monitoring.

PMID- 15976424
TI  - Radiological review of pneumothorax.

PMID- 15976425
TI  - Principles of war surgery.

PMID- 15976426
TI  - Programme budgeting and marginal analysis: bridging the divide between doctors
      and managers.

PMID- 15976427
TI  - Time for radical reform.

PMID- 15976428
TI  - Health inequalities under New Labour: difference in findings is due to
      geographical coverage.

PMID- 15976429
TI  - Health inequalities under New Labour: relative rather than absolute gaps are
      important over time and place.

PMID- 15976430
TI  - Pharmacogenetics and ethnically targeted therapies: racial drugs need to be put
      in context.

PMID- 15976431
TI  - Making allegations without due care is wrong.

PMID- 15976432
TI  - Detecting cheating in written medical examinations: self regulation may be way
      forward.

PMID- 15976433
TI  - Patients' written consent when photographed could suffice for journals.

PMID- 15976434
TI  - Younger teenagers are also at risk of mumps outbreaks.

PMID- 15976435
TI  - Shaving can be safer head lice treatment than insecticides.

PMID- 15976436
TI  - A testing time for ethical standards.

PMID- 15976438
TI  - Detecting cheating in written medical examinations: teach, and students may learn
      something.

PMID- 15976439
TI  - Telomeres: what's new at your end?

PMID- 15976440
TI  - Women in cell science. Elisabetta Dejana. Interview by Fiona Watt.

PMID- 15976441
TI  - Give lipids a START: the StAR-related lipid transfer (START) domain in mammals.
AB  - The steroidogenic acute regulatory protein (StAR)-related lipid transfer (START)
      domain is a protein module of approximately 210 residues that binds lipids,
      including sterols. Fifteen mammalian proteins, STARD1-STARD15, possess a START
      domain and these can be grouped into six subfamilies. Cholesterol, 25
      hydroxycholesterol, phosphatidylcholine, phosphatidylethanolamine and ceramides
      are ligands for STARD1/STARD3/STARD5, STARD5, STARD2/STARD10, STARD10 and
      STARD11, respectively. The lipids or sterols bound by the remaining 9 START
      proteins are unknown. Recent studies show that the C-terminal end of the domain
      plays a fundamental role, forming a lid over a deep lipid-binding pocket that
      shields the ligand from the external environment. The START domain can be
      regarded as a lipid-exchange and/or a lipid-sensing domain. Mammalian START
      proteins have diverse expression patterns and can be found free in the cytoplasm,
      attached to membranes or in the nucleus. They appear to function in a variety of
      distinct physiological processes, such as lipid transfer between intracellular
      compartments, lipid metabolism and modulation of signaling events. Mutation or
      misexpression of START proteins is linked to pathological processes, including
      genetic disorders, autoimmune disease and cancer.

PMID- 15976442
TI  - The vacuolar proton-ATPase plays a major role in several membrane-bounded
      organelles in Paramecium.
AB  - The vacuolar proton-ATPase (V-ATPase) is a multisubunit enzyme complex that is
      able to transfer protons over membranes against an electrochemical potential
      under ATP hydrolysis. The enzyme consists of two subcomplexes: V0, which is
      membrane embedded; and V1, which is cytosolic. V0 was also reported to be
      involved in fusion of vacuoles in yeast. We identified six genes encoding c
      subunits (proteolipids) of V0 and two genes encoding F-subunits of V1 and studied
      the role of the V-ATPase in trafficking in Paramecium. Green fluorescent protein
      (GFP) fusion proteins allowed a clear subcellular localization of c- and F
      subunits in the contractile vacuole complex of the osmoregulatory system and in
      food vacuoles. Several other organelles were also detected, in particular dense
      core secretory granules (trichocysts). The functional significance of the V
      ATPase in Paramecium was investigated by RNA interference (RNAi), using a
      recently developed feeding method. A novel strategy was used to block the
      expression of all six c- or both F-subunits simultaneously. The V-ATPase was
      found to be crucial for osmoregulation, the phagocytotic pathway and the
      biogenesis of dense core secretory granules. No evidence was found supporting
      participation of V0 in membrane fusion.

PMID- 15976443
TI  - The meiotic spindle of the Drosophila oocyte: the role of centrosomin and the
      central aster.
AB  - We provide here the first evidence that a distinct midzone is present in the
      Drosophila melanogaster female meiosis I spindle. This region has the ability to
      bind the Pavarotti kinesin-like (PAV-KLP) and Abnormal spindle (Asp) proteins,
      indicating a correct organization of the central spindle microtubules. We also
      identified the core component centrosomal protein centrosomin (CNN) at an
      unexpected site within the anaphase I spindle, indicating a role for CNN during
      the biogenesis of the female meiotic apparatus. However, there are no apparent
      defects in the midzone organization of cnn oocytes, whereas defects occur later
      when the central aster forms. The primary mutant phenotype of cnn oocytes is the
      failure to form a developed central microtubule organizing center (MTOC),
      although twin meiosis II spindles usually do form. Thus the central MTOC may not
      be essential for the formation of the inner poles of twin meiosis II spindles, as
      generally proposed, but it might be involved in maintaining their proper spacing.
      We discuss the proposal that, in the presence of a central MTOC, a chromatin
      driven mechanism of spindle assembly like that described during meiosis I may
      control the morphogenesis of the twin meiosis II spindles.

PMID- 15976444
TI  - Release of extracellular membrane particles carrying the stem cell marker
      prominin-1 (CD133) from neural progenitors and other epithelial cells.
AB  - Apical plasma membrane constituents of mammalian neural stem/progenitor cells
      have recently been implicated in maintaining their stem/progenitor cell state.
      Here, we report that in the developing embryonic mouse brain, the fluid in the
      lumen of the neural tube contains membrane particles carrying the stem cell
      marker prominin-1 (CD133), a pentaspan membrane protein found on membrane
      protrusions of the apical surface of neuroepithelial cells. Two size classes of
      prominin-1-containing membrane particles were observed in the ventricular fluid:
      approximately 600-nm particles, referred to as P2 particles, and 50-80-nm
      vesicles, referred to as P4 particles. The P2 and P4 particles appeared in the
      ventricular fluid at the very onset and during the early phase of neurogenesis,
      respectively. Concomitant with their appearance, the nature of the prominin-1
      containing apical plasma membrane protrusions of neuroepithelial cells changed,
      in that microvilli were lost and large pleiomorphic protuberances appeared. P4
      particles were found in various body fluids of adult humans, including saliva,
      seminal fluid and urine, and were released by the epithelial model cell line Caco
      2 upon differentiation. Importantly, P4 particles were distinct from exosomes.
      Our results demonstrate the widespread occurrence of a novel class of
      extracellular membrane particles containing proteins characteristic of stem
      cells, and raise the possibility that the release of the corresponding membrane
      subdomains from the apical surface of neural progenitors and other epithelial
      cells may have a role in tissue development and maintenance. Moreover, the
      presence of prominin-1-containing membrane particles in human body fluids may
      provide the basis for a protein-based diagnosis of certain diseases.

PMID- 15976445
TI  - Multiple regions of Crumbs3 are required for tight junction formation in MCF10A
      cells.
AB  - The formation and maintenance of tight junctions is essential for the development
      of epithelial cell polarity. Recently, a number of conserved polarity-regulating
      proteins have been shown to localize to epithelial tight junctions, and to play a
      role in the regulation of tight junction formation. The Crumbs3/PALS1/PATJ
      protein complex localizes at epithelial tight junctions and interacts with the
      polarity-regulating protein complex of Par6/Par3/aPKC. Overexpression of Crumbs3
      in MDCKII cells leads to a delay in tight junction formation in these cells,
      suggesting a role in the regulation of tight junction development. Here we report
      new evidence that Crumbs3 indeed plays an essential role in tight junction
      formation. Mammary MCF10A cells express little endogenous Crumbs3 and fail to
      form tight junctions when grown under standard tissue culture conditions. The
      staining pattern of ZO-1, a tight junction marker, is fragmented, and other tight
      junction markers show either fragmented junctional expression or diffuse
      cytoplasmic staining. Expression of exogenous Crumbs3 induces the formation of
      tight junction structures marked by smooth, continuous ZO-1 staining at apical
      cell-cell junctions. A number of other tight junction markers, including claudin
      1 and occludin, are also recruited to these junctions. Analysis by transmission
      electron microscopy and measurements of the transepithelial electrical resistance
      confirm that these structures are functional tight junctions. Mutations in either
      the Crumbs3 PDZ binding motif or the putative FERM binding motif lead to defects
      in the ability of Crumbs3 to promote tight junction development. Our results
      suggest that Crumbs3 plays an important role in epithelial tight junction
      formation, and also provide the first known functional role for the mammalian
      Crumbs FERM binding domain.

PMID- 15976446
TI  - Real-time dynamics of the F-actin cytoskeleton during secretion from chromaffin
      cells.
AB  - Transmitted light images showed an intricate and dynamic cytoplasmic structural
      network in cultured bovine chromaffin cells observed under high magnification.
      These structures were sensitive to chemicals altering F-actin-myosin and
      colocalised with peripheral F-actin, beta-actin and myosin II. Interestingly,
      secretagogues induced a Ca2+-dependent, rapid (>10 second) and transitory (60
      second cycle) disassembling of these cortical structures. The simultaneous
      formation of channel-like structures perpendicular to the plasmalemma conducting
      vesicles to the cell limits and open spaces devoid of F-actin in the cytoplasm
      were also observed. Vesicles moved using F-actin pathways and avoided diffusion
      in open, empty zones. These reorganisations representing F-actin transfer from
      the cortical barrier to the adjacent cytoplasmic area have been also confirmed by
      studying fluorescence changes in cells expressing GFP-beta-actin. Thus, these
      data support the function of F-actin-myosin II network acting simultaneously as a
      barrier and carrier system during secretion, and that transmitted light images
      could be used as an alternative to fluorescence in the study of cytoskeleton
      dynamics in neuroendocrine cells.

PMID- 15976447
TI  - Glucocorticoids remodel nuclear envelope structure and permeability.
AB  - The present study describes glucocorticoid induced remodelling of nuclear
      envelope (NE) structure and permeability. A glucocorticoid analogue,
      triamcinolone acetonide (TA), is injected into Xenopus laevis oocytes that
      express an exogeneous glucocorticoid receptor (GR). Electrical, fluorescence and
      nano-imaging techniques are applied to study the permeability and the structure
      of the NE at 5 and 60 minutes after injection of TA. A remarkable dilation of
      nuclear pore complexes (NPCs), a rearrangement of NPC distribution and a
      significant increase of NE permeability for ions and fluorescent 20 kDa dextran
      are observed within 5 minutes of TA exposure. At regular distances on local NE
      patches, NPCs seem to adjoin forming clusters each consisting of several hundred
      NPCs. Interestingly, at the same time of exposure, hydrophobicity of NPC central
      channels and NPC-free NE surface increases. The changes in permeability and
      structure are transient as the NE permeability returns to its initial state
      within 60 minutes. In conclusion, the NE is a barrier of high plasticity
      sensitive to hydrophobic molecules. Remodelling of NE structure and permeability
      is a prerequisite for mediating physiological actions of glucocorticoids.

PMID- 15976448
TI  - PHR1, an integral membrane protein of the inner ear sensory cells, directly
      interacts with myosin 1c and myosin VIIa.
AB  - By using the yeast two-hybrid technique, we identified a candidate protein ligand
      of the myosin 1c tail, PHR1, and found that this protein can also bind to the
      myosin VIIa tail. PHR1 is an integral membrane protein that contains a pleckstrin
      homology (PH) domain. Myosin 1c and myosin VIIa are two unconventional myosins
      present in the inner ear sensory cells. We showed that PHR1 immunoprecipitates
      with either myosin tail by using protein extracts from cotransfected HEK293
      cells. In vitro binding assays confirmed that PHR1 directly interacts with these
      two myosins. In both cases the binding involves the PH domain. In vitro
      interactions between PHR1 and the myosin tails were not affected by the presence
      or absence of Ca2+ and calmodulin. Finally, we found that PHR1 is able to
      dimerise. As PHR1 is expressed in the vestibular and cochlear sensory cells, its
      direct interactions with the myosin 1c and VIIa tails are likely to play a role
      in anchoring the actin cytoskeleton to the plasma membrane of these cells.
      Moreover, as both myosins have been implicated in the mechanotransduction slow
      adaptation process that takes place in the hair bundles, we propose that PHR1 is
      also involved in this process.

PMID- 15976449
TI  - A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule
      acetylation in osteoclasts.
AB  - Osteoclast maturation is accompanied by changes in podosome patterning, resulting
      in the formation of a peripheral belt, which requires an intact microtubule
      network. Here, we report that by inhibiting Rho, the podosome belt is maintained
      at the cell periphery despite depolymerisation of microtubules by nocodazole. Rho
      inhibition was correlated to the increase in microtubule stabilisation and
      microtubule acetylation. By microinjecting activated Rho or its activated
      effector mDia2 in osteoclasts, we found that the podosome belt was disrupted and
      the level of microtubule acetylation dramatically decreased. We further
      characterised the molecular mechanism responsible for microtubule deacetylation
      by co-immunoprecipitation experiments. We found that not only was mDia2
      coprecipitating with the recently identified microtubule deacetylase HDAC6 but
      that it also activated the microtubule deacetylase activity of HDAC6 in an in
      vitro deacetylase assay. Finally, we found that during osteoclastogenesis, there
      is a correlation between the increase in microtubule acetylation and the podosome
      belt stabilisation and that if Rho is inhibited in the early stages of osteoclast
      differentiation, it accelerates both microtubule acetylation and podosome belt
      stabilisation. Altogether, our data reveal a pathway in which Rho interferes with
      the osteoclast maturation process by controlling the level of microtubule
      acetylation and actin organisation through mDIA2 and HDAC6.

PMID- 15976450
TI  - PINCH1 regulates cell-matrix and cell-cell adhesions, cell polarity and cell
      survival during the peri-implantation stage.
AB  - PINCH1 is composed of 5 LIM domains, binds integrin-linked kinase (ILK) and
      locates to integrin-mediated adhesion sites. In order to investigate PINCH1
      function we generated mice and embryonic stem (ES) cell-derived embryoid bodies
      (EBs) lacking the PINCH1 gene. Similar to mice lacking beta1 integrin or Ilk,
      loss of PINCH1 arrested development at the peri-implantation stage. In contrast
      to beta1 integrin or Ilk mutants, however, disruption of the PINCH1 gene produced
      implantation chambers with visible cell clumps even at embryonic day 9.5. In
      order to define the phenotype leading to the peri-implantation lethality we made
      PINCH1-null EBs and found similar but also additional defects not observed in
      beta1 integrin or Ilk mutant EBs. The similarities included abnormal epiblast
      polarity, impaired cavitation and detachment of endoderm and epiblast from
      basement membranes. Additional defects, which were not observed in beta1 integrin
      or ILK-deficient mice or EBs, included abnormal cell-cell adhesion of endoderm
      and epiblast as well as the presence of apoptotic cells in the endodermal cell
      layer. Although ILK and PINCH1 were shown to be involved in the phosphorylation
      of serine-473 of PKB/Akt, immunostaining with specific antibodies revealed no
      apparent alteration of PKB/Akt phosphorylation in PINCH1-deficient EBs.
      Altogether these data demonstrate an important role of PINCH1 for integrin
      function, actin organization, cell-cell adhesion and endodermal cell survival
      during the implanting of mouse embryos.

PMID- 15976451
TI  - Candida albicans hyphae have a Spitzenkorper that is distinct from the polarisome
      found in yeast and pseudohyphae.
AB  - Fungi grow with a variety of morphologies: oval yeast cells, chains of elongated
      cells called pseudohyphae and long, narrow, tube-like filaments called hyphae. In
      filamentous fungi, hyphal growth is strongly polarised to the tip and is mediated
      by the Spitzenkorper, which acts as a supply centre to concentrate the delivery
      of secretory vesicles to the tip. In the budding yeast Saccharomyces cerevisiae,
      polarised growth is mediated by the polarisome, a surface cap of proteins that
      nucleates the formation of actin cables delivering secretory vesicles to the
      growing tip. The human fungal pathogen, Candida albicans, can grow in all three
      morphological forms. Here we show the presence of a Spitzenkorper at the tip of
      C. albicans hyphae as a ball-like localisation of secretory vesicles, together
      with the formin Bni1 and Mlc1, an ortholog of an S. cerevisiae myosin regulatory
      light chain. In contrast, in C. albicans yeast cells, pseudohyphae and hyphae
      Spa2 and Bud6, orthologs of S. cerevisiae polarisome components, as well as the
      master morphology regulator Cdc42, localise predominantly, but not exclusively,
      to a surface cap resembling the polarisome of S. cerevisiae yeast cells. A small
      amount of Cdc42 also localises to the Spitzenkorper. Furthermore, we show
      differences in the genetic and cytoskeletal requirements, and cell cycle dynamics
      of polarity determinants in yeast, pseudohyphae and hyphae. These results,
      together with the cytological differences between the cell types, suggest that
      the Spitzenkorper and polarisome are distinct structures, that the polarisome and
      Spitzenkorper coexist in hyphae, and that polarised growth in hyphae is driven by
      a fundamentally different mechanism to that in yeast and pseudohyphae.

PMID- 15976452
TI  - Characterization of the TGN exit signal of the human mannose 6-phosphate
      uncovering enzyme.
AB  - The human mannose 6-phosphate uncovering enzyme participates in the uncovering of
      the mannose 6-phosphate recognition tag on lysosomal enzymes, a process that
      facilitates recognition of those enzymes by mannose 6-phosphate receptors to
      ensure delivery to lysosomes. Uncovering enzyme has been identified on the trans
      Golgi network at steady state. It has been shown to traffic to the plasma
      membrane from where it is rapidly internalized via endosomal structures, the
      process being mediated by a tyrosine-based internalization motif, Y488HPL, in its
      cytoplasmic tail. Using immunogold electron microscopy a GFP-uncovering enzyme
      fusion construct was found to be colocalized with the cation-dependent mannose 6
      phosphate receptor in regions of the trans-Golgi network, suggesting that
      uncovering enzyme might follow a similar pathway of exit from the trans-Golgi
      network as that of the cation-dependent mannose 6-phosphate receptor. In this
      study, we identified the signal sequence in the cytoplasmic tail of uncovering
      enzyme responsible for its exit from the trans-Golgi network. Using GFP fusion
      constructs of the transmembrane and cytoplasmic domains of uncovering enzyme, we
      could show, by automated analysis of confocal immunofluorescence images, that
      residues Q492EMN in the cytoplasmic tail of uncovering enzyme are involved in its
      exit from the trans-Golgi network. Detailed characterization of the exit signal
      revealed that residue Q492 is the most important to the exit function while M494
      and N495 also contribute. The cytoplasmic tail of the uncovering enzyme does not
      possess any of the known canonical signal sequences for interaction with Golgi
      associated gamma ear-containing adaptor proteins. The identification of a trans
      Golgi network exit signal in its cytoplasmic tail elucidates the trafficking
      pathway of uncovering enzyme, a crucial player in the process of lysosomal
      biogenesis.

PMID- 15976453
TI  - DNA double-strand breaks and homology search: inferences from a species with
      incomplete pairing and synapsis.
AB  - The relationship between meiotic recombination events and different patterns of
      pairing and synapsis has been analysed in prophase I spermatocytes of the
      grasshopper Stethophyma grossum, which exhibit very unusual meiotic
      characteristics, namely (1) the three shortest bivalents achieve full synapsis
      and do not show chiasma localisation; (2) the remaining eight bivalents show
      restricted synapsis and proximal chiasma localisation, and (3) the X chromosome
      remains unsynapsed. We have studied by means of immunofluorescence the
      localisation of the phosphorylated histone H2AX (gamma-H2AX), which marks the
      sites of double-strand breaks; the SMC3 cohesin subunit, which is thought to have
      a close relationship to the development of the axial element (a synaptonemal
      complex component); and the recombinase RAD51. We observed a marked nuclear
      polarization of both the maturation of SMC3 cohesin axis and the ulterior
      appearance of gamma-H2AX and RAD51 foci, these being exclusively restricted to
      those chromosomal regions that first form cohesin axis stretches. This polarised
      distribution of recombination events is maintained throughout prophase I over
      those autosomal regions that are undergoing, or about to undergo, synapsis. We
      propose that the restricted distribution of recombination events along the
      chromosomal axes in the spermatocytes is responsible for the incomplete
      presynaptic homologous alignment and, hence, for the partial synaptonemal complex
      formation displayed by most bivalents.

PMID- 15976454
TI  - Matrix cell adhesion activation by non-adhesion proteins.
AB  - Cell adhesion to the extracellular matrix is important in many biological
      processes. Various ligands and cell surface receptors have been defined. In vitro
      cell adhesion to matrix proteins and to other 'adhesion' proteins is generally
      measured on plastic culture substrates. We have found that the presence of low
      levels of adhesion proteins, e.g. fibronectin, together with high concentrations
      of non-adhesion proteins, e.g. osteonectin, can promote cell attachment on
      plastic culture dishes. This promotion of adhesion occurs even when the
      concentrations of fibronectin, collagen and other adhesive proteins are too low
      to support cell attachment alone. Other non-adhesive proteins that have similar
      activity in 'triggering' the attachment of cells to low levels of adhesion
      molecules include bovine serum albumin (BSA) and cytochrome C. The non-adhesive
      protein must be added to the plate first, or together with the low amount of the
      adhesion protein, to 'activate' cell attachment. Adding the adhesion protein
      fibronectin to the plate first, followed by osteonectin, resulted in no
      'activation' of attachment. The non-adhesive protein did not bind to the adhesive
      protein nor did it alter the level of adhesive protein binding to the substrate.
      The non-adhesive protein did, however, expose integrin-binding sites of the
      adhesive protein fibronectin. These data confirm and extend previous data by
      others demonstrating the role of non-adhesive proteins in regulating the
      conformation and cell adhesive activity of matrix adhesion proteins on plastic
      surfaces. Such findings might explain contradictions in the literature about the
      activity of 'adhesive proteins'.

PMID- 15976455
TI  - Phospholipase D2 stimulates integrin-mediated adhesion via phosphatidylinositol 4
      phosphate 5-kinase Igamma b.
AB  - Cellular adhesion can be regulated by, as yet, poorly defined intracellular
      signalling events. Phospholipase D enzymes generate the messenger lipid
      phosphatidate and here we demonstrate that suppression of this reaction inhibits
      cellular adhesion. This effect was reversed by the addition of cell-permeable
      analogues of either phosphatidate or phosphatidylinositol 4,5-bisphosphate. By
      contrast, neither diacylglycerol nor lysophosphatidic acid were able to reverse
      this effect suggesting that phosphatidate itself acts directly on a target
      protein(s) to regulate adhesion rather than as the result of its conversion to
      either of these metabolite lipids. Antibodies that block beta1 and beta2 integrin
      substrate interactions inhibited adhesion stimulated by both phosphatidate and
      phosphatidylinositol 4,5-bisphosphate indicating that these lipids regulate beta1
      and beta2 integrin-mediated adhesion. In vivo, these lipids can be generated by
      phospholipase D2 and phosphatidylinositol 4-phosphate 5-kinase Igamma b,
      respectively, and over-expression of catalytically-functional forms of these
      enzymes dose-dependently stimulated adhesion while siRNA depletion of PLD2 levels
      inhibited adhesion. Furthermore the ability of over-expressed phospholipase D2 to
      stimulate adhesion was inhibited by a dominant-negative version of
      phosphatidylinositol 4-phosphate 5-kinase Igamma b. Consistent with this,
      phosphatidylinositol 4-phosphate 5-kinase Igamma b-mediated adhesion was
      dependent upon phospholipase D2's product, phosphatidate indicating that
      phosphatidylinositol 4-phosphate 5-kinase Igamma b is downstream of, and
      necessary for, phospholipase D2's regulation of adhesion. It is likely that this
      phospholipase D2-generated phosphatidate directly stimulates phosphatidylinositol
      4-phosphate 5-kinase Igamma b to generate phosphatidylinositol 4,5-bisphosphate
      as this mechanism has previously been demonstrated in vitro. Thus, our data
      indicates that during the initial stages of adhesion, phospholipase D2-derived
      phosphatidate stimulates phosphatidylinositol 4-phosphate 5-kinase Igamma b to
      generate phosphatidylinositol 4,5-bisphosphate and that consequently this
      inositol phospholipid promotes adhesion through its regulation of cell-surface
      integrins.

PMID- 15976456
TI  - The C-terminus of prestin influences nonlinear capacitance and plasma membrane
      targeting.
AB  - Prestin is a unique molecular-motor protein expressed in the lateral plasma
      membrane of outer hair cells (OHC) in the organ of Corti of the mammalian
      cochlea. It is thought that prestin undergoes conformational changes driven by
      the cell's membrane potential. The resulting alterations in OHC-length are
      assumed to constitute the cochlear amplifier. Prestin is a member of the anion
      solute carrier family 26 (SCL26A), but it is different from other family members
      in its unique function of voltage-driven motility. Because the C-terminus is the
      least conserved region in the family, we investigated its influence with a series
      of deletion, point and chimeric mutants. The function and cellular expression of
      mutants were examined in a heterologous expression system by measurement of
      nonlinear capacitance (NLC) and immunofluorescence. Each mutant produced a unique
      mixture of patterns of cell morphologies, which were classified as to the
      location of prestin within the cell. The data from deletion mutants (Del516,
      Del525, Del630, Del590, Del709, Del719) revealed that nearly the full length
      (>708 amino acids) of the protein was required for normal prestin expression and
      function. Since most deletion mutations eliminated plasma membrane targeting,
      chimeric proteins were constructed by fusing prestin, at amino acid 515 or 644,
      with the homologous portion of the C-terminus from the two most closely related
      SLC26A members, pendrin and putative anion exchanger 1. These chimeric proteins
      were again improperly (but differently) targeted than simple truncation mutants,
      and all lacked functional phenotype. When two of the potential basolateral
      membrane-targeting motifs were mutated (Y520A/Y526A), incomplete plasma membrane
      expression was seen. We also show that some double point mutations (V499G/Y501H)
      fully express in the plasma membrane but lack NLC. These non-charged amino acids
      may have unrevealed important roles in prestin's function. Together, these data
      suggest that certain specific sequences and individual amino acids in the C
      terminus are necessary for correct cellular distribution and function.

PMID- 15976457
TI  - Three-dimensional simulations of airways within human lungs.
AB  - Information regarding the deposition patterns of inhaled particles has important
      implications to the fields of medicine and risk assessment. The former concerns
      the targeted delivery of inhaled pharmacological drugs (aerosol therapy); the
      latter concerns the risk assessment of inhaled air pollutants (inhalation
      toxicology). It is well documented in the literature that the behavior and fate
      of inhaled particles may be formulated using three families of variables:
      respiratory system morphologies, aerosol characteristics, and ventilatory
      parameters. It is straightforward to propose that the seminal role is played by
      morphology per se because the structures of individual airways and their spatial
      orientations within lungs affect the motion of air and the trajectories of
      transported particles. In previous efforts, we have developed original algorithms
      to describe airway networks within lungs and employed them as templates to
      interpret the results of single photon emission computed tomography (SPECTs)
      studies. In this work, we have advanced the process of mathematical modeling and
      computer simulations to produce three-dimensional (3D) images. We have tested the
      new in silico model by studying two different branching concepts: an inclusive
      (all airways present) system and a single "typical" pathway system. When viewed
      with the glasses supplied with this volume, the 3D nature of airway branching
      networks within lungs as displayed via our original computer graphics software is
      clear. We submit that the new technology will have numerous and seminal functions
      in future medical and toxicological regimens, the most fundamental being the
      creation of a platform to view natural 3D structures in vivo with related
      biological processes (e.g., disposition of inhaled pharmaceuticals).

PMID- 15976458
TI  - Direct transfer of NADH from malate dehydrogenase to complex I in Escherichia
      coli.
AB  - During aerobic growth of Escherichia coli, nicotinamide adenine dinucleotide
      (NADH) can initiate electron transport at either of two sites: Complex I (NDH-1
      or NADH:ubiquinone oxidoreductase) or a single-subunit NADH dehydrogenase (NDH
      2). We report evidence for the specific coupling of malate dehydrogenase to
      Complex I. Membrane vesicles prepared from wild type cultures retain malate
      dehydrogenase and are capable of proton translocation driven by the addition of
      malate + NAD. This activity was inhibited by capsaicin, an inhibitor specific to
      Complex I, and it proceeded with deamino-NAD, a substrate utilized by Complex I,
      but not by NDH-2. The concentration of free NADH produced by membrane vesicles
      supplemented with malate + NAD was estimated to be 1 microM, while the rate of
      proton translocation due to Complex I was consistent with a somewhat higher
      concentration, suggesting a direct transfer mechanism. This interpretation was
      supported by competition assays in which inactive mutant forms of malate
      dehydrogenase were able to inhibit Complex I activity. These two lines of
      evidence indicate that the direct transfer of NADH from malate dehydrogenase to
      Complex I can occur in the E. coli system.

PMID- 15976459
TI  - 5-HT induction of c-fos gene expression requires reactive oxygen species and Rac1
      and Ras GTPases.
AB  - Serotonin (5-HT) stimulates superoxide release, phosphorylation of p42/p44
      mitogen-activated protein kinase (MAPK), and DNA synthesis in bovine pulmonary
      artery smooth muscle cells. Both p42/p44 MAPK and reactive oxygen species (ROS)
      generation are required for 5-HT-induced growth in SMC. Agents that block the
      production of ROS, or ROS scavengers, block MAPK activation by 5-HT. However,
      specific signal transduction by 5-HT leading to proteins that control entrance
      into the cell cycle are not well defined in smooth muscle cells. Here, we show by
      Western blot that 5-HT upregulates c-Fos, an immediate early gene product known
      to regulate the entrance of quiescent cells into the cell cycle. Northern blots
      showed that c-fos mRNA is induced by 5-HT in 30 min. This induction is blocked by
      PD98059, indicating that activation of MAPK is required. 5-HT-induced expression
      of a 350 bp c-fos promoter in a luciferase reporter is blocked by PD98059 and
      diphenyliodonium (DPI). The GTPases Rac1 and Ras have been implicated in growth
      factor-induced generation of ROS. Overexpression of either dominant negative (DN)
      Rac1 or DN Ras inhibited 5-HT-mediated c-fos promoter activation. 5-HT also
      induced expression from a truncated c-fos promoter containing an isolated serum
      response element. This activation was blocked by DPI and PD98059. Overexpression
      of activated Ras and Rac1 were additive for activation of the serum response
      element promoter. Regulation of cyclin D1, a protein shown to be regulated by c
      fos and required for entry into the cell cycle, is upregulated by 5-HT and is
      blocked by DPI and PD98059. Nuclear factor-kappaB, which can also regulate cyclin
      D1, was not activated. We conclude that 5-HT stimulates c-fos and cyclin D1
      expression through a ROS-dependent mechanism that requires Ras, Rac1, and MAPK.

PMID- 15976460
TI  - Osmosis and solute-solvent drag: fluid transport and fluid exchange in animals
      and plants.
AB  - In 1903, George Hulett explained how solute alters water in an aqueous solution
      to lower the vapor pressure of its water. Hulett also explained how the same
      altered water causes osmosis and osmotic pressure when the solution is separated
      from liquid water by a membrane permeable to the water only. Hulett recognized
      that the solute molecules diffuse toward all boundaries of the solution
      containing the solute. Solute diffusion is stopped at all boundaries, at an open
      unopposed surface of the solution, at a semipermeable membrane, at a container
      wall, or at the boundary of a solid or gaseous inclusion surrounded by solution
      but not dissolved in it. At each boundary of the solution, the solute molecules
      are reflected, they change momentum, and the change of momentum of all reflected
      molecules is a pressure, a solute pressure (i.e., a force on a unit area of
      reflecting boundary). When a boundary of the solution is open and unopposed, the
      solute pressure alters the internal tension in the force bonding the water in its
      liquid phase, namely, the hydrogen bond. All altered properties of the water in
      the solution are explained by the altered internal tension of the water in the
      solution. We acclaim Hulett's explanation of osmosis, osmotic pressure, and
      lowering of the vapor pressure of water in an aqueous solution. His explanation
      is self-evident. It is the necessary, sufficient, and inescapable explanation of
      all altered properties of the water in the solution relative to the same property
      of pure liquid water at the same externally applied pressure and the same
      temperature. We extend Hulett's explanation of osmosis to include the osmotic
      effects of solute diffusing through solvent and dragging on the solvent through
      which it diffuses. Therein lies the explanations of (1) the extravasation from
      and return of interstitial fluid to capillaries, (2) the return of luminal fluid
      in the proximal and distal convoluted tubules of a kidney nephron to their
      peritubular capillaries, (3) the return of interstitial fluid to the vasa recta,
      (4) return of aqueous humor to the episcleral veins, and (5) flow of phloem from
      source to sink in higher plants and many more examples of fluid transport and
      fluid exchange in animal and plant physiology. When a membrane is permeable to
      water only and when it separates differing aqueous solutions, the flow of water
      is from the solution with the lower osmotic pressure to the solution with the
      higher osmotic pressure.

PMID- 15976461
TI  - Humanity's quest for knowledge--open access--the IJO initiative.

PMID- 15976462
TI  - Dry eye: prevalence and attributable risk factors in a hospital-based population.
AB  - PURPOSE: To study the prevalence of dry eye in a hospital-based population and to
      evaluate the various risk factors attributable to dry eye. MATERIALS AND METHODS:
      In this cross-sectional study, 500 patients above 20 years of age were screened
      randomly for dry eye. A 13-point questionnaire, Lissamine Green test, Tear film
      break-up time (TBUT), Schirmer's test and presence of strands/filaments were used
      to diagnose dry eye. The diagnosis was made when at least three of the tests were
      positive. The role of air pollution, sunlight, excessive winds, smoking, drugs
      and refractive status as dry eye risk factors was assessed. RESULTS: Ninety-two
      (18.4%) patients had dry eye. Dry eye prevalence was maximum in those above 70
      years of age (36.1%) followed by the age group 31-40 years (20%). It was
      significantly higher (P = 0.024) in females (22.8%) than in males (14.9%), more
      common in rural residents (19.6%) than in urban (17.5%) and highest among
      farmers/labourers (25.3%). A 2.15 fold increase was found in the odds for dry eye
      in those exposed to excessive wind, 1.91 fold to sunlight exposure, 1.42 to
      smoking, 1.38 to air pollution and 2.04 for persons on drugs. Dry eye prevalence
      was 14% in emmetropes, 16.8% in myopes and 22.9% in hypermetropes. It was 15.6%
      in those with corrected and 25.3% in those with uncorrected refractive errors.
      CONCLUSION: Dry eye is an under-diagnosed ocular disorder. Reduction in the
      modifiable risk factors of dry eye is essential to reduce its prevalence.

PMID- 15976463
TI  - Visual outcomes of pan-retinal photocoagulation in diabetic retinopathy at one
      year follow-up and associated risk factors.
AB  - PURPOSE: To assess the visual outcomes at one-year follow-up after pan-retinal
      photocoagulation (PRP) in type 2 diabetes mellitus subjects with proliferative
      diabetic retinopathy (PDR) and associated risk factors. MATERIALS AND METHODS: A
      retrospective study, using data from medical records of 5000 Type 2 diabetic
      patients who underwent a retinal examination between 1995 and 1999 at a diabetic
      centre. Ocular, clinical and biochemical parameters were assessed at baseline and
      at one-year follow-up after PRP. Diabetic retinopathy (DR) was documented by
      colour photography and PRP was performed according to the ETDRS criteria.
      RESULTS: PRP was done in 413 eyes, of which 261 eyes of 160 subjects were
      eligible for the study. One hundred and forty eyes (73%) of 191 eyes with good
      visual acuity (6/9) at baseline maintained the same vision at one-year follow-up.
      Of the 53 eyes with visual acuity of 6/12-6/36 at baseline, 58.5% (31 eyes)
      maintained same vision and 18.9% (10 eyes) improved their vision at one-year
      follow-up. Of the 17 eyes with visual acuity < or =6/60 at baseline, 12
      maintained the same vision and the remaining 5 improved their vision. The causes
      of visual loss included vitreous haemorrhage in 20 subjects (31.7%), progression
      of cataract in 19 (30%), chronic macular oedema in 15 (23.8%), pre-retinal
      haemorrhage in the macula in 6 (9.5%) and pre-retinal fibrosis in the macula in 3
      (4.7%) subjects. On multiple logistic regression analysis, diastolic blood
      pressure (P =0.03), duration of diabetes (P =0.006), fasting blood glucose (P
      =0.02) and nephropathy (P =0.01) were associated with decreased vision after PRP.
      Glycated haemoglobin (HbA1c) (P < 0.001), serum creatinine (P =0.03), HDL
      cholesterol (P =0.05), diabetic neuropathy (P < 0.001), hypertension (P =0.01)
      and diabetic nephropathy (P < 0.001) showed a significant association with PDR.
      CONCLUSION: Visual acuity at baseline, the duration of diabetes and proteinuria
      played a significant role in determining the post-PRP visual acuity.

PMID- 15976464
TI  - Role of photodynamic therapy in polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate photodynamic Therapy (PDT) with Verteporfin for polypoidal
      choroidal vasculopathy (PCV) involving the fovea in Indian eyes, through a
      retrospective interventional case series. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 9 patients (9 eyes) diagnosed to have PCV
      with foveal involvement between September 2001 and October 2002. RESULTS: Nine
      eyes underwent PDT for PCV. Follow-up ranged from 12 to 16 months. Initial visual
      acuity (VA) ranged from 1/60 to 6/12 and final VA varied from 1/60 to 6/9 at the
      end of follow-up. VA improved in 4/9 eyes (44.4%) by one line and remained
      unchanged in 5/9 eyes (55.6%), hence it was considered stabilized in all eyes. No
      adverse effects or events were observed during or after treatment with
      verteporfin. CONCLUSION: PDT may be beneficial for PCV with foveal involvement.
      Its long-term efficacy requires to be evaluated.

PMID- 15976465
TI  - Amplitude of accommodation and its relation to refractive errors.
AB  - AIMS: To evaluate the relationship between amplitude of accommodation and
      refractive errors in the peri-presbyopic age group. MATERIALS AND METHODS: Three
      hundred and sixteen right eyes of 316 consecutive patients in the age group 35-50
      years who attended our outpatient clinic were studied. Emmetropes, hypermetropes
      and myopes with best-corrected visual acuity of 6/6 J1 in both eyes were
      included. The amplitude of accommodation (AA) was calculated by measuring the
      near point of accommodation (NPA). In patients with more than +/- 2 diopter
      sphere correction for distance, the NPA was also measured using appropriate soft
      contact lenses. RESULTS: There was a statistically significant difference in AA
      between myopes and hypermetropes (P < 0.005) and between myopes and emmetropes (P
      < 0.005) in the 35-39 year age group. In the 40-44 year age group, there was a
      significant difference in AA between emmetropes and hypermetropes (P < 0.0001),
      emmetropes and myopes (P < 0.01) and hypermetropes and myopes (P < 0.0001). In
      patients above 45 years of age there was no significant difference (P > 0.5).
      CONCLUSION: Our study showed higher amplitude of accommodation among myopes
      between 35 and 44 years compared to emmetropes and hypermetropes.

PMID- 15976466
TI  - Primary adult human retinal pigment epithelial cell cultures on human amniotic
      membranes.
AB  - PURPOSE: Retinal pigment epithelial (RPE) cells grow well on surfaces that
      provide an extracellular matrix. Our aim was to establish primary adult human RPE
      cell cultures that retain their epithelial morphology in vitro using human
      amniotic membrane (hAM) as substrate. MATERIALS AND METHODS: Human cadaver
      eyeballs (16) were obtained from the eye bank after corneal trephination. RPE
      cells were harvested by a) mechanical dissection of the inner choroid surface
      (10, group 1) or by b) enzymatic digestion using 0.25% Trypsin/0.02% EDTA (6,
      group 2). The cells were explanted onto de-epithelialized hAM, nourished using
      DMEM/HAMS F-12 media and monitored for growth under the phase contrast
      microscope. Cell cultures were characterised by whole mount studies and paraffin
      sections. Growth data in the two groups were compared using the students' 't'
      test. RESULTS: Eleven samples (68.75%) showed positive cultures with small,
      hexagonal cells arising from around the explant which formed a confluent and
      progressively pigmented monolayer. Whole mounts showed closely placed polygonal
      cells with heavily pigmented cytoplasm and indistinct nuclei. The histologic
      sections showed monolayers of cuboidal epithelium with variable pigmentation
      within the cytoplasm. Growth was seen by day 6-23 (average 11.5 days) in the
      mechanical group, significantly earlier (P < 0.025) than in the enzymatic group
      (day 29-35, average 31.6 days). CONCLUSIONS: Primary adult human RPE cell
      cultures retain epithelial morphology in vitro when cultured on human amniotic
      membranes. Mechanical dissection of the inner choroid surface appears to be an
      effective method of isolating RPE cells and yields earlier growth in cultures as
      compared to isolation by enzymatic digestion.

PMID- 15976467
TI  - Role of early radial optic neurotomy in central retinal vein occlusion.
AB  - PURPOSE: To determine safety, clinical and visual results, and potential
      complications of early radial optic neurotomy (RON) surgery in eyes with central
      retinal vein occlusion (CRVO), with relative afferent pupillary defect and visual
      acuity MATERIALS AND METHODS: This prospective, interventional case-series
      included 24 patients of CRVO who underwent RON within 2 months of disease onset.
      The preoperative examination included slitlamp biomicroscopy, fundus photography
      and fluorescein angiography. Foveal thickness was measured using optical
      coherence tomography (OCT) in the last 6 eyes only. In each case, RON was
      performed after informed consent. Two radial incisions were placed in the nasal
      quadrant of the optic disc, using a micro-vitreoretinal blade. The postoperative
      change in vision, clinical picture, fundus photographs, angiograms and foveal
      thickness by OCT were the main outcome variables studied. The Wilcoxan signed
      test was used to assess the results. RESULTS: Average symptom duration was 37.8
      +/- 15.2 days (range 15-60 days, median: 34.5 days) and follow-up 7.7 +/- 2.1
      months (range 1-12 months, median: 8 months). Visual outcome: 2 (8.33%) eyes each
      had fall and preservation of pre-RON visual acuity respectively. Twenty eyes
      (83.33%) showed increase in vision (of average 3 lines). Pre and postoperative
      vision ranged from 0.017-0.1 (average:0.061) and 0.017-0.667 (average: 0.17)
      respectively (P < 0.05). Clinical and angiographic outcome: decline in macular
      oedema, decreased or resolved intraretinal haemorrhages, resolution of venous
      dilatation and disc oedema could be appreciated in all cases. Foveal thickness:
      average pre and postoperative foveal thickness was 834.17 microm and 556.17
      microm respectively (P < 0.05) in the 6 eyes where it was measured before and
      after RON. One eye developed retinal-detachment. CONCLUSION: Radial optic
      neurotomy is better than the natural course in eyes with CRVO, with vision <
      6/60.

PMID- 15976468
TI  - Phacoemulsification after penetrating keratoplasty with autologous limbal
      transplant and amniotic membrane transplant in chemical burns.
AB  - We report a patient who had earlier penetrating keratoplasty with amniotic
      membrane transplant and autologous limbal cell transplant for chemical injury who
      underwent cataract surgery by phacoaspiration. A posterior limbal incision with
      corneal valve was made superotemporally with extreme caution to avoid damage to
      the limbal graft. Aspiration flow rates and vacuum were kept low to avoid any
      turbulence during surgery. A 6.0 mm optic diameter acrylic foldable intraocular
      lens was inserted in the bag. The patient achieved a best-corrected visual acuity
      of 6/12 at 10 months' follow-up with a clear corneal graft. We conclude that
      caution during wound construction and phacoaspiration can help preserve corneal
      and limbal graft integrity in patients undergoing cataract surgery after corneal
      graft and limbal transplantation.

PMID- 15976469
TI  - Chronic microsporidial stromal keratitis in an immunocompetent, non-contact lens
      wearer.
AB  - An 82-year-old healthy man with unilateral chronic stromal keratitis, initially
      diagnosed to have viral keratitis and refractory to medical therapy, showed
      numerous oval, microsporidial organisms, measuring 4-5 m in length in the corneal
      biopsy. Penetrating keratoplasty, followed by treatment with systemic albendazole
      and topical propamidine isethionate resulted in resolution of the infection.
      Electron microscopy of the keratoplasty specimen demonstrated sporoblasts with
      diplokaryotic nuclei and multiple coils of the filament. The light and electron
      microscopic features were consistent with microsporidial keratitis.

PMID- 15976470
TI  - Double prepapillary arterial loops associated with superior branch macular artery
      occlusion.
AB  - Prepapillary arterial loops are congenital vascular anomalies that have been
      noted to cause arterial occlusions. We report a case of superior branch macular
      artery occlusion in an eye with two independent prepapillary arterial loops,
      following a Valsalva-like mechanism.

PMID- 15976471
TI  - Premacular haemorrhage associated with arteriovenous communications of the retina
      induced by a valsalva-like mechanism: an observational case report.
AB  - A 26-year-old woman presented with sudden defective vision in the right eye
      following lifting a heavy bucket of water. Examination showed a dense premacular
      subhyaloid haemorrhage associated with arteriovenous communications of the retina
      (AVCRs). Spontaneous absorption of the premacular haemorrhage with consequent
      improvement in the visual acuity was seen after two months. The possible
      aetiopathogenesis of the case is also discussed.

PMID- 15976472
TI  - Photodynamic therapy of a posttraumatic choroidal neovascular membrane.
AB  - The authors present a patient with posttraumatic choroidal neovascular membrane
      (CNVM) treated with PDT resulting in regression of the CNVM.

PMID- 15976473
TI  - Acute bilateral central serous chorioretinopathy following intra-articular
      injection of corticosteroid.
AB  - There is increasing evidence in the literature implicating the use of exogenous
      steroids through various routes as a risk factor for the development of
      idiopathic central serous chorioretinopathy (ICSC). We report a case of acute
      bilateral ICSC following intra-articular injection of corticosteroids.

PMID- 15976474
TI  - Status of speciality training in ophthalmology in India.
AB  - PURPOSE: To systematically evaluate the quality of ophthalmology training in
      India. METHODS: Questionnaires were sent to existing medical schools and
      accredited training institutions. Institutions were followed up thrice to obtain
      responses. Data were analysed using Stata 8.0. RESULTS: Responses were received
      from 128 (89.5%) of the 143 institutions. Each year, 900 training slots were
      available across the country. Faculty: student ratios were better in accredited
      training institutions than in postgraduate medical schools. Fifty three (41.4%)
      of 128 institutions subscribed to more than 2 international journals. Fewer than
      1 in 6 institutions conducted research projects. 11 (8.6%) institutions reported
      more than five publications in international peer-reviewed journals over three
      years. Only a third of the responding institutions had a wet lab. CONCLUSIONS:
      There is a need to improve the training facilities and optimally utilise the
      infrastructure available in postgraduate medical schools.

PMID- 15976476
TI  - Epidemiological and microbiological diagnosis of suppurative keratitis in
      Gangetic West Bengal, eastern India.

PMID- 15976477
TI  - Speciation of coagulase negative Staphylococcus causing bacterial keratitis.

PMID- 15976479
TI  - Probing in children older than 13 months.

PMID- 15976481
TI  - Spectacle frame induced irritant contact dermatitis.

PMID- 15976483
TI  - Offspring from non-stimulated calves at an age younger than two months: a
      preliminary report.
AB  - This study investigated the viability of embryos from non-stimulated 2-3-month
      old calves generated in vitro using oocytes from follicles of defined size in
      terms of their ability to produce full-term pregnancies. Ablation of
      follicles>or=4 mm was used to induce the emergence of a new follicular wave, and
      calves (n=3) were laparoscopically punctured three times at 7-day-intervals to
      recover cumulus-oocyte-complexes (COCs) from follicles>8 (group A) and between 4
      8 mm (group B). Calves were aged 49, 56, and 80 days, respectively, at first
      recovery. Morphologically intact COCs were subjected to in vitro maturation,
      fertilization, and embryo culture, and compact morulae/blastocysts were
      transferred on day 7 post-insemination to synchronized virgin heifers. Blood
      typing was used for maternity analysis. A total of 29 COCs were recovered, 21
      cultured, yielding 11 cleaved embryos (52.4%) and 6 compact morulae/blastocysts
      (28.6%). No differences were observed between groups. Transfer of the 6 embryos
      to 5 recipients resulted in three pregnancies (one from group A and two from
      group B). Two normal male offspring (both from group B), with birth weights of 44
      and 51 kg, were born, and two donor calves, aged 56 and 59 days, were identified
      as the dams. In conclusion, the results demonstrate that embryos generated in
      vitro from oocytes from non-stimulated calves at an age younger than two months
      are viable in terms of their ability to produce full-term pregnancies, and
      suggest that the viability of calf embryos is not related to follicle size.

PMID- 15976484
TI  - Regulation of endometrial fibroblast growth factor 7 (FGF-7) and its receptor
      FGFR2IIIb in gilts after sex steroid replacements, and during the estrous cycle
      and early gestation.
AB  - The aim of this study was to characterize the effect of ovarian steroids and
      early gestation on the expression of fibroblast growth factor 7 (FGF-7) and its
      receptor (FGFR2IIIb) in the porcine endometrium. In Experiment 1, gilts were
      ovariectomized (OVX) on day 10 of the estrous cycle and treated thereafter with
      vehicle (VEH), progesterone (P4), estradiol benzoate (EB), or P4+EB. Days 12 and
      20 cyclic gilts (C12 and C20) were used to determine the influence of
      physiologically low and high plasma estradiol and progesterone concentrations on
      their expression. In Experiment 2, the expression of FGF-7 and FGFR2IIIB was
      characterized on days 1 (G 1) and 12 (G 12) of gestation. FGF-7 and FGFR2IIIb
      mRNA were quantified by quantitative real-time RT-PCR, and localization of FGF-7
      protein in steroid-treated and early pregnant gilts was performed by
      immunohistochemistry. VEH-gilts expressed both FGF-7 and FGFR2IIIB mRNA. We found
      a significant effect of EB, but no effects of P4 or P4+EB on the mRNA expression
      of FGF-7. FGFR2IIIb mRNA significantly decreased after the EB and combined P4+EB
      treatments, compared to P4 only substituted animals. Day 12 cyclic gilts showed
      significantly higher FGF-7 and FGFR2IIIb mRNA expression compared with day 20
      gilts. Between day 1 and 12 of gestation, FGF-7 mRNA expression differed highly
      while FGFR2IIIb transcripts only varied significantly. FGF-7 protein was
      localized in endometrial epithelia, vascular smooth muscle, and the endothelium
      of different types of blood vessels. Staining was weak in VEH and P4 treated
      gilts, whereas it was prominent following EB and P4+EB. FGF-7 antibody strongly
      stained the luminal epithelium on day 12 of gestation. In summary, FGF-7 and
      FGFR2IIIb mRNA expression is regulated differently by exogenous ovarian steroids,
      assuming progesterone in connection with a specific amount of 17beta-estradiol,
      whereas the receptor seems to be inhibited by estradiol. Both transcripts
      coordinately increased during the progesterone dominated phase on day 12 both in
      cyclic and early pregnant gilts. We conclude that estradiol and progesterone are
      involved in the regulation of this ligand-receptor system, which might have an
      important role in preparing endometrial tissue for implantation in gilts.

PMID- 15976485
TI  - Antimicrobial peptides in Drosophila: structures, activities and gene regulation.
AB  - The production of antimicrobial peptides (AMPs) is an important aspect of host
      defence in multicellular organisms. Biochemical analysis of the hemolymph of the
      fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of
      eight classes of AMPs. These peptides can be grouped into three families based on
      their main biological targets, gram-positive bacteria (defensin), gram-negative
      bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin,
      metchnikowin). Drosophila AMPs are synthesized by the fat body in response to
      infection, and secreted into the blood. Most of them can also be induced in
      surface epithelia in a tissue-specific manner. Finally, some of them are
      constitutively expressed in defined tissues, such as the salivary glands or the
      reproductive tract. We review here the structures and activities of these AMPs,
      as well as the signalling cascades, which lead to their induction upon detection
      of infectious non-self.

PMID- 15976486
TI  - Antimicrobial peptides in human skin.
AB  - Human skin is permanently exposed to a wide variety of potential harmful
      microorganisms. Despite these microbial threats, skin is surprisingly highly
      resistant against infections. Various studies in the last decade discovered a
      chemical cutaneous defense system based on the production of antimicrobial
      proteins. These antimicrobial proteins act as a first defense line through their
      broad spectrum of potent antimicrobial activity. In addition to constitutively
      expressed antimicrobial proteins, production of various antimicrobial proteins in
      keratinocytes is induced by bacterial compounds as well as proinflammatory
      cytokines. The resulting local accumulation of antimicrobial proteins offers a
      fast and very efficient way to prevent microbes from establishing an infection.
      In this review we summarize the current status of our knowledge of expression of
      antimicrobial proteins in human skin.

PMID- 15976487
TI  - Human defensins in Crohn's disease.
AB  - Crohn's disease, a transmural inflammation of the gut, has been linked to good
      childhood hygiene, frequent use of antibiotics before diagnosis, adherent or
      invasive mucosal bacteria and a break in the tolerance of luminal bacteria. A
      decrease or lack of mucosal peptide antibiotics may play a central role in the
      etiopathogenesis of Crohn's disease. The dysregulated adaptive immune system may
      reflect only the primary break of the mucosal defence since the immune response
      is mostly directed against luminal bacteria. Crohn's disease patients with ileal
      involvement, as compared to controls and Crohn's disease patients without ileal
      disease, are characterized by a diminished expression of the ileal Paneth cell
      defensins. This decrease is even more pronounced in Crohn's disease patients with
      a mutation in the NOD2 gene, which is associated with Crohn's disease and ileal
      involvement. NOD2 is an intracellular peptidoglycan receptor and is expressed in
      Paneth cells. In contrast to ulcerative colitis, Crohn's disease of the colon is
      characterized by an impaired induction of human beta defensins 2 and 3. The
      hypothesis of an impaired mucosal antibacterial activity is also consistent with
      the benefit from antibiotic or probiotic treatment in certain disease states.

PMID- 15976488
TI  - Antimicrobial peptides in lung inflammation.
AB  - Antimicrobial peptides (AMPs) are expressed in the respiratory tract and act as
      effector substances of the innate immune system. A variety of cells synthesize
      and secrete AMPs including epithelial and professional host defense cells such as
      neutrophils, macrophages, and NK cells. In the human lung, beta-defensins
      originate from epithelial cells, macrophages and lymphocytes. alpha-defensins are
      synthesized by neutrophils. LL-37/hCAP-18 is produced by epithelial cells,
      neutrophils, lymphocytes, and macrophages. AMPs act as endogenous antibiotics by
      direct destruction of microorganisms. Recently, it became clear that AMPs bind to
      cellular receptors and activate a variety of cell types such as airway epithelial
      cells, endothelial cells, mast cells, macrophages, dendritic cells, and
      neutrophils amongst others. Concentrations of AMPs in lung secretions are altered
      in several pulmonary diseases. This chapter describes the basic and applied
      biology of AMPs in the human lung and their potential role in pulmonary disease.

PMID- 15976489
TI  - Bacterial evasion of innate defense at epithelial linings.
AB  - The evolution of multicellular organisms has been, and continues to be,
      paralleled by the evolution of the surrounding microbial flora. This intimate
      coexistence between higher host organisms and microbes has generated a myriad of
      adaptation strategies at both sides to cope with, or even benefit from the given
      conditions. On the host side, the development of an effective immune defence
      system allowed the maintenance of an astonishingly stable homeostasis on many
      body sites, and even the establishment of sterile surfaces at vulnerable
      anatomical sites. On the other hand, microbial diversity has led to the
      establishment of a large number of microbial life styles that allow persistence
      and proliferation in the presence of host defense mechanisms. The following
      review describes bacterial strategies to circumvent or modify host defenses that
      operate at the epithelial lining. It illustrates the enormous diversity of
      mechanisms that are part of the complex interplay between microbial organisms and
      the host. It also reflects the dramatic progress made in the understanding of the
      mammalian immune defense system which many times has been initiated by the
      surprising results from the study of microbial pathogenesis.

PMID- 15976490
TI  - Recognition of bacterial products by toll-like receptors.
AB  - Over the past 5 years, our knowledge about how the immune system senses the
      microbial world has changed fundamentally. It has been known for decades that
      microbial products such as lipopolysaccharide or bacterial DNA have a profound
      activity on human cells. Whereas the molecular structure of many different
      pathogenic microbial compounds has been extensively studied and characterized,
      the molecular basis of their recognition by the immune system remained elusive
      for a long time. It was the late Charles Janeway who developed the idea of
      microbial structures forming pathogen-associated molecular patterns (PAMP) that
      would be recognized by pattern-recognition receptors [1]. Even if the notion of
      pattern recognition is challenged today, the discovery of the family of Toll
      receptors in species as diverse as Drosophila and humans, and the identification
      of their role in distinguishing molecules and structures that are common to
      microorganisms has led to a renewed appreciation of the innate immune system.
      This review focuses on the current knowledge about the different molecules that
      are recognized by Toll receptors in mammalian cells.

PMID- 15976491
TI  - TLR signalling and the function of dendritic cells.
AB  - The recognition of microbes by innate immune cells initiates activation of the
      whole immune system. Toll-like receptors (TLRs) are known to recognize various
      components of invading pathogens. At present, the natural ligands for almost all
      TLR members have been identified. TLRs are expressed on many types of cells
      including macrophages and dendritic cells (DCs). The recognition of invading
      microbes by TLRs on DCs induces proinflammatory cytokine production and enhanced
      antigen presentation to naive T cells, and finally activates antigen-specific
      adaptive immune responses. The sequential activation of innate and subsequent
      adaptive immunity are crucial steps to eradicate invading pathogens. Recently,
      the TLR signalling pathway has been intensively investigated. Accumulating
      evidence indicates that, at least, four adaptor molecules are involved in TLR
      signalling and provide their signalling specificities. Distinct TLR ligands
      provide distinct activation status and cytokine production patterns for antigen
      presenting cells, resulting in the induction of differential immune responses.
      Thus, TLRs are critical molecules to induce not only inflammatory responses but
      also fine-tuned adaptive immune responses depending on invading pathogens.

PMID- 15976492
TI  - Immunosurveillance by gammadelta T cells: focus on the murine system.
AB  - Physiologic immune responses are an integration of the activities of several
      lymphoid cell types that include qualitatively distinct T cell subsets. The
      contributions that specific T cell subsets make during infection, inflammation,
      and carcinogenesis is becoming increasingly clear from a variety of mouse models
      and, importantly, their backcrossing onto different genetic backgrounds. This
      review considers what we have learned in the mouse about the crucial roles played
      by gammadelta T cells. We consider how the cells' associations with specific
      tissues have revealed that T cell responses are regulated locally as well as
      systemically, and we discuss the implications of this for understanding and
      enhancing immune surveillance in the clinical setting.

PMID- 15976493
TI  - gammadelta T cells link innate and adaptive immune responses.
AB  - While most T cells use a CD3-associated alpha/beta T cell receptor as antigen
      recognition structure, a second population of T cells expresses the alternative
      gamma/delta T cell receptor. gamma/delta T cells are a minor population in the
      peripheral blood but constitute a major population among intestinal
      intraepithelial lymphocytes. Most gamma/delta T cells recognize ligands which are
      fundamentally different from the short peptides that are seen by alpha/beta T
      cells in the context of MHC class I or class II molecules. Thus, human Vdelta2 T
      cells recognize small bacterial phosphoantigens, alkylamines and synthetic
      aminobisphosphonates, whereas Vdelta1 T cells recognize stress-inducible MHC
      related molecules MICA/B as well as several other ligands. At the functional
      level, gamma/delta T cells rapidly produce a variety of cytokines and usually
      exert potent cytotoxic activity, also towards many tumor cells. In this article,
      we discuss the role of gamma/delta T cells as a bridge between the innate and the
      adaptive immune system, based on the interpretation that gamma/delta T cells use
      their T cell receptor as a pattern recognition receptor. Our increasing
      understanding of the ligand recognition and activation mechanisms of gamma/delta
      T cells also opens new perspectives for the development of gamma/delta T cell
      based immunotherapies.

PMID- 15976495
TI  - Tacrolimus and nonsteroidal anti-inflammatory drugs: an association to be
      avoided.
AB  - BACKGROUND: Tacrolimus (FK) and nonsteroidal anti-inflammatory drugs (NSAIDs) can
      cause acute nephrotoxicity. The expanding use of tacrolimus and the intense
      consumption of NSAIDS increase the chances of their simultaneous use. METHODS:
      Rats receiving a nonselective COX inhibitor (diclofenac, D) and FK or a selective
      COX-2 inhibitor (rofecoxib, RO) and FK were treated with FK (2 mg/kg/day), D (10
      mg/kg/day), RO (3 mg/kg/day), FK+D, FK+RO and vehicle for 7 days on low-salt
      diet. RESULTS: Both associations significantly impaired glomerular filtration
      rate (GFR; 0.63 +/- 0.06 ml/min/100 g in FK+D, 0.83 +/- 0.06 ml/min/100 g in
      FK+RO) which did not occur with single drug therapy (0.98 +/- 0.03 ml/min/100 g
      in D, 1.06 +/- 0.04 ml/min/100 g in RO, 0.99 +/- 0.05 ml/min/ 100 g in FK) or
      vehicle (1.10 +/- 0.05 ml/min/100 g). GFR decrease was significantly higher with
      FK+D. GFR impairment occurred without RBF or RVR major changes. Mild tubular
      vacuolization and dilatation and acute degenerative changes were observed in
      tubular cells. FK+D animals showed a marked weight loss, not observed in the
      other groups. FK+NSAIDs association decreased FK blood levels (1.73 +/- 0.3 ng/ml
      in FK+D, 1.8 +/- 0.3 ng/ml in FK+RO, 3.2 +/- 0.4 ng/ml in FK, p < 0.05).
      CONCLUSIONS: The association of FK and nonselective or COX-2 selective NSAIDs in
      salt-depleted animals caused a significant GFR impairment and decreased FK blood
      levels.

PMID- 15976496
TI  - Divergent regulation of circulating and intrarenal renin-angiotensin systems in
      response to long-term blockade.
AB  - BACKGROUND/AIMS: Long-term treatment with angiotensin-converting enzyme (ACE)
      inhibitors or angiotensin (Ang) II type I (AT(1)) receptor blockers can improve
      kidney function and attenuate the progressive decline in kidney function
      associated with age. In this study in Wistar rats medicated for 22 months, we
      determined the effects of enalapril (10 mg/kg/day) and losartan (30 mg/kg/day)
      treatment, in comparison with vehicle (tap water), on renal AngII receptor
      density and circulating and urinary components of the renin-angiotensin system
      (RAS). METHODS: Kidney sections were incubated with [(125)I-sarcosine(1)
      threonine(8)]AngII (0.6 nM) for Ang receptor density, and Ang peptides were
      determined using radioimmunoassays. RESULTS: Receptor density was approximately
      50% higher in vasa recta, glomeruli, and tubulointerstitium in enalapril-treated
      rats and lower in vasa recta and glomeruli in losartan-treated relative to
      vehicle-treated rats. Losartan and enalapril treatment elevated plasma levels of
      AngI and Ang-(1-7) while AngII increased only in losartan-treated rats. In
      contrast, both treatments were associated with a reduction in urinary excretion
      of all three Ang peptides as compared with control rats. CONCLUSION: The
      reduction in urinary Ang peptides with losartan and enalapril treatment suggests
      that blockade of intrarenal AngII may be an important mechanism underlying the
      renoprotection seen with such treatments.

PMID- 15976497
TI  - Sketches of otohistory. Part 9: presby[a]cusis.

PMID- 15976498
TI  - A systematic review of the associations between age and sex and the operative
      risks of carotid endarterectomy.
AB  - BACKGROUND: Randomized trials of carotid endarterectomy (CEA) for both
      symptomatic and asymptomatic carotid stenosis have demonstrated that benefit is
      decreased in women, due partly to a high operative risk, which is independent of
      age. However, it is uncertain whether these trial-based observations are
      generalisable to routine clinical practice. METHODS: We performed a systematic
      review of all publications reporting data on the association between age and/or
      sex and procedural risk of stroke and/or death following CEA from 1980 to 2004.
      RESULTS: 62 eligible papers reported relevant data. Females had a higher rate of
      operative stroke and death (25 studies, OR = 1.31, 95% CI = 1.17-1.47, p < 0.001)
      than males, but no increase in operative mortality (15 studies, OR = 1.05, 95% CI
      = 0.81-0.86, p = 0.78). Compared with younger patients, operative mortality was
      increased at > or =75 years (20 studies, OR = 1.36, 95% CI = 1.07-1.68, p =
      0.02), at age > or =80 years (15 studies, OR = 1.80, 95% CI = 1.26-2.45, p <
      0.001) and in older patients overall (35 studies, OR = 1.50, 95% CI = 1.26-1.78,
      p < 0.001). In contrast, risk of non-fatal stroke did not increase with age and
      so the combined perioperative risk was only slightly increased at age > or =75
      years (21 studies, OR = 1.18, 95% CI = 0.94-1.44, p = 0.06), at age > or =80
      years (10 studies, OR = 1.14, 95% CI = 0.92-1.36, p = 0.34) and in older patients
      overall (36 studies, OR = 1.17, 95% CI = 1.04-1.31, p = 0.01). CONCLUSIONS: The
      effects of age and sex on the operative risk of CEA in published case series are
      consistent with those observed in the trials. Operative risk of stroke is
      increased in women and operative mortality is increased in patients aged > or =75
      years.

PMID- 15976499
TI  - Antithrombotic management after an ischemic stroke in French primary care
      practice: results from three pooled cross-sectional studies.
AB  - BACKGROUND AND PURPOSE: We aimed at quantifying and explaining the underuse of
      antithrombotic treatments after an ischemic stroke in patients seen in French
      primary care. METHODS: We pooled all ischemic stroke patients included in 3
      observational primary care-based observational studies. French general
      practitioners and cardiologists recruited 14,544 patients with atherothrombotic
      disease including 4,322 with an ischemic stroke. Antithrombotic therapies and
      risk factors were prospectively recorded. Patients with atrial fibrillation (AF)
      were considered appropriate for oral anticoagulants (OAC) and those without AF
      for antiplatelet drugs. RESULTS: Out of the 4,322 stroke patients, 3,732 (86.3%)
      were taking at least one antithrombotic drug. Among the 765 patients with AF, 333
      (43.5%) received OAC and 2,718 (86.9%) out of the 3,129 patients appropriate for
      antiplatelet drug were taking antiplatelet drug. Multivariate analyses did not
      single out any risk factors for nonuse of OAC and showed that female sex (OR =
      1.48; IC 95%: 1.14-1.92) was associated with nonuse of antiplatelet drugs.
      Conversely, past myocardial infarction (OR = 0.44; IC 95%: 0.26-0.71) and
      hypercholesterolemia (OR = 0.64; IC 95%: 0.50-0.81) were associated with
      appropriate use of antiplatelet drugs. CONCLUSION: More than 50% of stroke
      patients with AF do not receive OAC and 15% of those without AF do not receive
      antiplatelet drugs. These findings are not satisfactorily explained by the main
      patients' characteristics and practitioner's speciality and underline the
      complexity of the process which allows the transfer of scientific evidence in
      clinical practice.

PMID- 15976500
TI  - A family support organiser for stroke patients and their carers: a randomised
      controlled trial.
AB  - BACKGROUND: Previous trials of interventions to support stroke survivors and
      their families in the community have had contradictory and inconclusive results.
      Using the MRC Framework for Complex Interventions we developed a family support
      organiser (FSO) service and refined outcome measures for evaluation. We tested
      the effects of the intervention in a randomised controlled trial. METHODS: From 1
      March 1999 to 1 April 2001 all first-in-a-lifetime strokes (n = 513) were
      identified and 340 (96%) of eligible strokes randomised to receive FSO or usual
      care. Patients and their carers were followed up at 3 months and 1 year post
      stroke. Outcomes included satisfaction (main outcome) with hospital staff and
      outpatient services, use of social services, reintegration to normal living
      (RNLI) and feelings about life after the stroke. RESULTS: The mean number of
      contacts with the FSO was 15 (SD = 9.8) per patient. More intervention than
      control patients received some social services and had increased patient and
      carer satisfaction in most aspects, particularly with information about recovery
      and feeling that someone had listened. There was little evidence at 3 or 12
      months of differences in RNLI. CONCLUSIONS: A meta-analysis of trials in this
      area is now needed along with further trials of interventions in subgroups of the
      stroke population to fully identify any benefits of the FSO role.

PMID- 15976501
TI  - Significance of silent infarcts in acute ischemic stroke patients aged 80 years
      and older.
AB  - BACKGROUND: The significance of silent infarcts (SIs) is unknown in very elderly
      patients with first-ever acute ischemic stroke. METHODS: Fifty patients aged 80
      years and older with first-ever acute ischemic stroke were studied. The
      conventional risk factors for stroke, the scores of age-related white matter
      changes, and the findings on echocardiography were compared between patients with
      and without SIs. RESULTS: Thirty-eight patients (76%) had one or more SIs. The
      patients without SIs frequently had atrial fibrillation (50% vs. 13.2%, p =
      0.014) or spontaneous echo contrast or thrombi on echocardiography (57.1% vs. 0%,
      p = 0.026) and showed lower scores on age-related white matter changes (0.5 +/-
      0.67 vs. 1.13 +/- 0.58, p = 0.002) than did patients with SIs. There were no
      differences in other risk factors for stroke between the two groups. CONCLUSION:
      In patients aged 80 years and older, the absence of SIs with a first-ever acute
      ischemic stroke may suggest the presence of cardiac embolic sources or atrial
      fibrillation.

PMID- 15976502
TI  - A DNA sequence polymorphism in the endoglin gene is not associated with
      intracranial aneurysm or aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Endoglin is a member of the transforming growth factor
      beta family of proteins and plays a central role in vascular growth and
      development. There have been conflicting reports that polymorphic variation in
      the endoglin gene is a risk factor for intracranial aneurysms (IAs). We sought to
      further investigate the intron 7 5'-TCCCCC-3' endoglin polymorphism as a risk
      factor for IA and subarachnoid hemorrhage (SAH) in a population of patients from
      western Pennsylvania. METHODS: We genotyped 98 IA patients and 191 unaffected
      controls for a length polymorphism in intron 7 using PCR-based methods. RESULTS:
      The endoglin polymorphism was not associated with IA or the incidence of aneurysm
      rupture and SAH. No association was found when data were stratified by smoking
      and hypertension. CONCLUSION: These data, from a population recruited in western
      Pennsylvania, support recent findings in Japanese and German populations that,
      despite earlier observation to the contrary, endoglin is not associated with IA.
      Furthermore, our study extends previous observations by demonstrating no
      association between endoglin and either IA or SAH regardless of whether data were
      stratified for modifiable risk factors such as smoking and hypertension.

PMID- 15976503
TI  - Neurotransplantation of fetal porcine cells in patients with basal ganglia
      infarcts: a preliminary safety and feasibility study.
AB  - BACKGROUND: Cell transplantation is safe in animal models and enhances recovery
      from stroke in rats. METHODS: We studied the safety and feasibility of fetal
      porcine transplantation in 5 patients with basal ganglia infarcts and stable
      neurological deficits. To prevent rejection, cells were pretreated with an anti
      MHC1 antibody and no immunosuppressive drugs were given to the patients. RESULTS:
      The first 3 patients had no adverse cell, procedure, or imaging-defined effects.
      The fourth patient had temporary worsening of motor deficits 3 weeks after
      transplantation, and the fifth patient developed seizures 1 week after
      transplantation. MRI in both patients demonstrated areas of enhancement remote
      from the transplant site, which resolved on subsequent imaging. Two patients
      showed improvement in speech, language, and/or motor impairments over several
      months and persisted at 4 years. The study was terminated by the FDA after the
      inclusion of 5 patients. CONCLUSION: This is the first report on the
      transplantation of nontumor cells in ischemic stroke patients.

PMID- 15976504
TI  - The Alzheimer variant of lewy body disease: a pathologically confirmed case
      control study.
AB  - The objective of the study was to identify clinical features that distinguish
      patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer's
      disease (AD) patients, from patients with AD. We examined a group of 27 patients
      from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem
      found to have DLB. For the present study, we compared cognitive, noncognitive and
      neurological symptoms between the two groups. We found that there were no
      differences on ratings of dementia and scales for activities of daily living.
      Patients with DLB performed better on the MMSE and the memory subtest of the
      CAMCOG, but there was no difference in any other cognitive domain. Furthermore,
      genetic risk factors, including family history of dementia or allele frequency of
      the apolipoprotein epsilon4, did not discriminate between the two groups, and
      there were no differences on CCT scans. Taken together, our findings suggest that
      Lewy body pathology may be present in patients who do not show the typical
      clinical features which distinguish DLB from AD.

PMID- 15976505
TI  - Disease management in multiple sclerosis.

PMID- 15976506
TI  - Selective COX-2 inhibitors and risk of myocardial infarction.
AB  - Selective inhibitors of cyclooxygenase-2 (COX-2, 'coxibs') are highly effective
      anti-inflammatory and analgesic drugs that exert their action by preventing the
      formation of prostanoids. Recently some coxibs, which were designed to exploit
      the advantageous effects of non-steroidal anti-inflammatory drugs while evading
      their side effects, have been reported to increase the risk of myo cardial
      infarction and atherothrombotic events. This has led to the withdrawal of
      rofecoxib from global markets, and warnings have been issued by drug authorities
      about similar events during the use of celecoxib or valdecoxib/parecoxib,
      bringing about questions of an inherent atherothrombotic risk of all coxibs and
      consequences that should be drawn by health care professionals. These questions
      need to be addressed in light of the known effects of selective inhibition of COX
      2 on the cardiovascular system. Although COX-2, in contrast to the cyclooxygenase
      1 (COX-1) isoform, is regarded as an inducible enzyme that only has a role in
      pathophysiological processes like pain and inflammation, experimental and
      clinical studies have shown that COX-2 is constitutively expressed in tissues
      like the kidney or vascular endothelium, where it executes important
      physiological functions. COX-2-dependent formation of prostanoids not only
      results in the mediation of pain or inflammatory signals but also in the
      maintenance of vascular integrity. Especially prostacyclin (PGI(2)), which exerts
      vasodilatory and antiplatelet properties, is formed to a significant extent by
      COX-2, and its levels are reduced to less than half of normal when COX-2 is
      inhibited. This review outlines the rationale for the development of selective
      COX-2 inhibitors and the pathophysiological consequences of selective inhibition
      of COX-2 with special regard to vasoactive prostaglandins. It describes coxibs
      that are current ly available, evaluates the current knowledge on the risk of
      atherothrombotic events associated with their intake and critically discusses the
      consequences that should be drawn from these insights.

PMID- 15976507
TI  - Role of the adventitia in the cyclic GMP-mediated relaxant effect of N-hydroxy-L
      arginine in rat aorta.
AB  - N(omega)-hydroxy-L-arginine (L-NOHA), the stable intermediate of the nitric oxide
      synthase (NOS)-catalyzed reaction, can induce NO/cyclic GMP-dependent relaxation
      in the rat aorta, in an endothelium- and NOS-independent manner. In this study,
      the role of the adventitia in the endothelium-independent effect of L-NOHA was
      investigated. Despite a decrease in norepinephrine (NE)-induced precontraction,
      adventitia removal in the rat aorta did not markedly alter the relaxant effect of
      forskolin, S-nitroso-N-acetylpenicillamine or glyceryl trinitrate. In contrast,
      both inhibition of NE-induced contraction and relaxation of NE-precontracted
      rings produced by L-NOHA were diminished in the absence of adventitia. Moreover,
      exposure to L-NOHA significantly enhanced the cyclic GMP level in the media of
      the aorta with, but not without adventitia. These findings demonstrate the role
      of the adventitia in the L-NOHA-induced decrease in tone and increase in cyclic
      GMP in the endothelium-denuded rat aorta. They suggest that NO or an NO-related
      compound formed from L-NOHA in the adventitia may produce paracrine effects.

PMID- 15976508
TI  - Survival benefit of recombinant human erythropoietin administration prior to
      onset of end-stage renal disease: variations across surrogates for quality of
      care and time.
AB  - BACKGROUND: Recombinant human erythropoietin (rHuEPO) is recommended pre-dialysis
      to correct the anemia of chronic kidney disease. This study evaluated the impact
      of pre-dialysis rHuEPO on mortality in incident end-stage renal disease (ESRD)
      patients with varying levels of pre-ESRD care. METHODS: The study included 15,807
      individuals whose exposure to rHuEPO was determined from HCFA 2728 forms.
      RESULTS: Median follow-up after starting dialysis was 32.8 months. Pre-ESRD
      rHuEPO use occurred in only 3,994 (25.3%) subjects and was more common in
      individuals with insurance, currently employed, started on outpatient dialysis,
      and initiated on peritoneal dialysis. During the study, 8,608 (54.5%) patients
      died. The risk of death was lower for rHuEPO-treated patients versus non-treated
      (relative risk 0.87, 95% CI 0.82-0.92). The survival benefit with rHuEPO was
      greatest early after dialysis initiation (relative risk at 1 vs. 7 years post
      dialysis 0.73, 95% CI 0.66-0.80 vs. 0.87, 95% CI 0.82-0.92, respectively), did
      not vary across several surrogates for quality of care, and was greatest in those
      with the highest achieved hematocrit pre-ESRD. CONCLUSION: Pre-dialysis rHuEPO
      confers a survival benefit that depends on achieved hematocrit and diminishes
      post-dialysis, but is independent of several surrogates for quality of care
      except for insurance status pre-ESRD.

PMID- 15976509
TI  - Renal damage susceptibility and autoregulation in RF-1 and RF-5 congenic rats.
AB  - BACKGROUND: Linkage analyses of crosses of rats susceptible to renal damage, fawn
      hooded hypertensive (FHH), and those resistant to kidney damage, August x
      Copenhagen Irish (ACI), indicated that five quantitative trait loci (QTLs), Rf-1
      to Rf-5, influence proteinuria (UPV), albuminuria (UAV) and focal
      glomerulosclerosis (FGS). Here we present data obtained in congenic rats to
      directly assess the role of the Rf-1 and Rf-5 QTLs. METHODS: Renal damage (UPV,
      UAV, and FGS) was assessed in ACI, ACI.FHH-(D1Rat324-D1Rat156)(Rf-1B), and
      ACI.FHH-(D17Rat117-D17Arb5)(D17Rat180-D17Rat51) (Rf-5) congenic rats in the two
      kidney (2K) control situation, and following L-NAME-induced hypertension,
      unilateral nephrectomy (UNX), and UNX combined with L-NAME. In addition we
      investigated renal blood flow (RBF) autoregulation in 2K congenic and parental
      ACI and FHH rats. RESULTS: Compared to ACI, Rf-1B congenic rats showed a
      significant increase in susceptibility to renal damage after all three
      treatments. The increase was most pronounced after UNX with L-NAME. In contrast,
      the degree of renal damage in Rf-5 congenic rats was not different from the ACI.
      Like FHH, Rf-1B rats had impaired renal autoregulation. In contrast, RBF
      autoregulation of Rf-5 rats does not differ from ACI. CONCLUSION: The Rf-5 QTL
      does not show any direct effect. The Rf-1 QTL carries one or more genes impairing
      renal autoregulation and influencing renal damage susceptibility. Whether these
      are the same genes remains to be established.

PMID- 15976510
TI  - Oxidative stress decreases klotho expression in a mouse kidney cell line.
AB  - BACKGROUND/AIMS: Defects in klotho gene expression in the mouse result in a
      syndrome that resembles human aging. We recently identified expression of klotho
      in a mouse inner medullary collecting duct (mIMCD3) cell line for the first time,
      and in the present study we explored the physiological relevance of the
      regulation of klotho expression in the presence of oxidant stress injury.
      METHODS: Klotho expression was analyzed by real-time PCR, Western blot, and
      immuocytochemical staining during exposure to hydrogen peroxide (H2O2).
      Overexpression of the klotho gene was induced by klotho adenoviruses, and the
      number of apoptotic cells was counted by flowcytometry. RESULTS: Oxidant stress
      injury by H2O2 dose-dependently reduced klotho expression and diminished klotho
      staining. There were fewer apoptotic cells among the klotho-transfected cells
      than among the control cells. CONCLUSION: Klotho is expressed in cell line
      mIMCD3, and the klotho gene may be involved in the process of oxidative stress
      injury and apoptosis in this cell line.

PMID- 15976511
TI  - Neuropharmacological therapy of carcinoid syndrome.

PMID- 15976512
TI  - Progesterone-receptive beta-endorphin and dynorphin B neurons in the arcuate
      nucleus project to regions of high gonadotropin-releasing hormone neuron density
      in the ovine preoptic area.
AB  - Progesterone inhibits gonadotropin-releasing hormone (GnRH) secretion through
      interneuronal systems located in the mediobasal hypothalamus in ewes. Endogenous
      opioid peptides are implicated in this inhibition of GnRH secretion. The
      distributions of endogenous opioid peptides are known to overlap with
      progesterone receptors (PR) in the arcuate nucleus. We investigated whether PR is
      expressed by beta-endorphin and dynorphin B neurons in the arcuate nucleus and if
      a subset of double-labeled cells projects to the preoptic area where most GnRH
      neurons are detected. Injection of a retrograde tracer, Fluorogold, into the
      rostral preoptic area was performed in ovariectomized ewes pretreated with
      estrogen and progesterone. Brain sections were processed using double
      immunocytochemistry. Only brains of ewes with an injection site encompassing at
      least 80 GnRH neurons were processed for PR and then either beta-endorphin or
      dynorphin B immunocytochemistry. Antigen retrieval is essential for PR detection
      but causes Fluorogold to fade. Thus, quantitative analysis was performed on
      photographs taken before and after antigen retrieval. We found that 25-30% of PR
      containing neurons, 20% of beta-endorphin cells and 22% of dynorphin B neurons in
      the arcuate nucleus project toward the preoptic area. From the PR/beta-endorphin
      double-labeled cells that represent 25 and 36% of PR and beta-endorphin cells,
      respectively, 35% were labeled with Fluorogold. From the PR/dynorphin B double
      labeled cells that account for 39 and 62% of PR and dynorphin B neurons,
      respectively, 26% contained Fluorogold. These data strongly support the
      hypothesis that progesterone acts in the arcuate nucleus through beta-endorphin
      and dynorphin B neurons to affect preoptic area GnRH neurons.

PMID- 15976513
TI  - Outcome of pregnancy in a patient with Gitelman syndrome: a case report.
AB  - Gitelman syndrome (GS) is an autosomal-recessive condition characterized by
      hypokalaemia, hypomagnesaemia and hypocalciuria. Though it affects women of child
      bearing age very little information is available about its impact on maternal and
      fetal outcome. We describe the course of pregnancy in a patient with GS which was
      characterized by a sixfold increase in potassium and magnesium requirements with
      inability to achieve normal levels despite intravenous supplementation. There was
      no adverse impact on the course of pregnancy or fetal outcome. The case
      highlights the variability in the phenotypic presentation of GS and recommends
      frequent monitoring of electrolytes with supplementation guided by clinical
      requirements without aiming to achieve normal blood levels.

PMID- 15976514
TI  - Two-piece, dual-purpose comprehensive contact lens for vitreous surgery.
AB  - PURPOSE: To describe a dual-purpose lens that can be used both as a planoconcave
      direct-image lens and wide-angle lens. This lens provides good resolution, is
      autoclavable and self-stabilizing. DESIGN: New instrument design. METHOD: This
      lens has two components (lenses): the inferior element is a modification of the
      standard, self-stabilizing planoconcave, one-piece acrylic lens with 4 footplates
      and is used in a similar manner; the superior part is a biconvex glass lens in a
      high-temperature-resistant plastic casing. The superior plastic casing is screwed
      on the inferior lens to convert it into a wide-angle lens. The lens is used as a
      self-stabilizing, planoconcave or wide-angle lens and is sterilized by
      autoclaving. RESULT: The planoconcave direct-image inferior lens gives a high
      resolution image with a field of view of 20 degrees. The wide-angle lens on
      assembly of the inferior and superior parts gives a static field of view of 80
      degrees and a dynamic field of view of 98 degrees. CONCLUSION: The two-piece dual
      purpose contact lens is an inexpensive substitute for both planoconcave and
      traditional wide-angle lens without compromising the stability and quality of the
      fundus image.

PMID- 15976515
TI  - Pharmacological and functional characterization of endothelin receptors in bovine
      trabecular meshwork and ciliary muscle.
AB  - To clarify the potential role of endothelin-1 (ET-1) in the pathogenesis of
      glaucoma, the endothelin receptors expressed in bovine trabecular meshwork (TM)
      and ciliary muscle (CM) were identified. TM and CM strips were subjected to ET-1
      as well as to specific endothelin receptor antagonists. In both tissues BQ123, a
      specific ET-A receptor antagonist, substantially inhibited ET-1-induced
      contraction. BQ788, a specific ET-B receptor antagonist, showed only moderate
      effects. Both ET receptor types were detected in bovine TM and CM using Western
      blot analysis. ET-1 produced an increase in intracellular calcium in cultured TM
      cells. This effect was inhibited by BQ123, but not by BQ788. Thus, although both
      receptors are present, the ET-A receptor appears to play the predominant role in
      mediating contraction in both the TM and CM, while the ET-B receptor seems to
      contribute little to the overall ET-1 effect.

PMID- 15976517
TI  - Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence
      and adulthood: a theoretical review.
AB  - BACKGROUND: Despite good evidence that ethanol abuse in adulthood is more likely
      the earlier human adolescents begin drinking, it is unclear why the early onset
      of drinking occurs in the first place. A review of experimental studies with
      animals complemented by clinical, epidemiologic and experimental studies with
      humans supports the idea that precipitating conditions for ethanol abuse occur
      well before adolescence, in terms of very early exposure to ethanol as a fetus or
      infant. Experimental studies with animals indicate, accordingly, that ethanol
      intake during adolescence or adulthood is potentiated by much earlier exposure to
      ethanol as a fetus or infant. METHODS: Two broad theoretical frameworks are
      suggested to explain the increase in affinity for ethanol that follows very early
      exposure to ethanol, one based on effects of mere exposure and the other on
      associative conditioning. Studied for 50 years or more in several areas of
      psychology, "effects of mere exposure" refers to enhanced preference expressed
      for flavors, or just about any stimuli, that are relatively familiar. An
      alternative framework, in terms of associative conditioning, is guided by this
      working hypothesis: During ethanol exposure the fetus or infant acquires an
      association between ethanol's orosensory (odor/taste) and pharmacological
      consequences, causing the animal subsequently to seek out ethanol's odor and
      taste. RESULTS AND CONCLUSIONS: The implication that ethanol has rewarding
      consequences for the fetus or young infant is supported by recent evidence with
      perinatal rats. Paradoxically, several studies have shown that such early
      exposure to ethanol may in some circumstances make the infant treat ethanol
      related events as aversive, and yet enhanced intake of ethanol in adolescence is
      nevertheless a consequence. Alternative interpretations of this paradox are
      considered among the varied circumstances of early ethanol exposure that lead
      subsequently to increased affinity for ethanol.

PMID- 15976518
TI  - Ethanol modulation of TNF-alpha biosynthesis and signaling in endothelial cells:
      synergistic augmentation of TNF-alpha mediated endothelial cell dysfunctions by
      chronic ethanol.
AB  - Despite reported cardio-protective effects of low alcohol intake, chronic
      alcoholism remains a risk factor in the pathogenesis of coronary artery disease.
      Dose related bimodal effects of alcohol on cardiovascular system might reflect
      contrasting influences of light versus heavy alcohol consumption on the vascular
      endothelium. Chronic ethanol induced damage to various organs has been linked to
      the increased release of TNF-alpha (TNF). We have previously shown that TNF,
      expressed at the sites of arterial injury, suppresses re-endothelialization of
      denuded arteries and inhibits endothelial cell (EC) proliferation in vitro. Here
      we report that in vitro chronic ethanol exposure enhances agonist-induced TNF
      mRNA and protein expression in EC. Ethanol-mediated increment in TNF expression
      involves increased de novo transcription without affecting mRNA stability. DNA
      binding assays revealed that ethanol-induced TNF up regulation was AP1 dependent.
      Functionally, TNF induced EC dysfunction, including reduced proliferation,
      migration and cyclin A expression, were all markedly enhanced in the presence of
      ethanol. Additionally, expression of cyclin D1 was significantly attenuated in
      cells co-treated with TNF and ethanol while each treatment alone had little
      effect on cyclin D1 expression. Furthermore, exposure to ethanol potentiated and
      prolonged agonist-induced activation of JNK. Inhibition of JNK by over-expression
      of dominant negative JNK1 substantially reversed ethanol/TNF-mediated inhibition
      of cyclin A expression and EC proliferation, suggesting modulation of JNK1
      signaling as the mechanism for ethanol/TNF-induced EC dysfunctions. Taken
      together, these data indicate that chronic ethanol consumption may negatively
      influence post angioplasty re-endothelialization thereby contributing to the
      development of restenosis.

PMID- 15976519
TI  - Effects of finasteride on chronic and acute ethanol withdrawal severity in the
      WSP and WSR selected lines.
AB  - BACKGROUND: The neurosteroid allopregnanolone (ALLO) is a potent positive
      modulator of gamma-aminobutyric acidA (GABAA) receptors that can modulate ethanol
      (EtOH) withdrawal. The 5alpha-reductase inhibitor finasteride blocks the
      formation of ALLO from progesterone and was recently found to reduce certain
      effects of EtOH. Using the Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure
      Resistant (WSR) selected lines, in the present studies we examined the effect of
      finasteride on acute and chronic EtOH withdrawal severity. METHODS: In the first
      two studies, male WSP and WSR mice were exposed to 72-hr EtOH vapor or air and
      received four injections of finasteride (50 mg/kg intraperitoneal (IP) or vehicle
      24 hr before and each day of the vapor exposure. After removal from the
      inhalation chamber, mice were scored for handling-induced convulsions (HICs)
      hourly for 12 hr and then again at 24 hr (study 1) or were tested on the elevated
      plus maze at 24 hr after removal from the inhalation chamber (study 2). In the
      third experiment, mice were pretreated with finasteride or vehicle 24 hr before
      an acute dose of EtOH (4 g/kg ip) or saline and then were tested for HICs as in
      the chronic study. RESULTS: In both chronic EtOH studies, finasteride
      pretreatment reduced EtOH withdrawal severity, measured by HICs, and anxiety
      related behavior, but only in the WSP selected line. However, finasteride
      pretreatment also significantly decreased blood EtOH concentration on the
      initiation of withdrawal in both chronic EtOH studies in WSP and WSR mice. In
      contrast, pretreatment with finasteride slightly enhanced acute EtOH withdrawal
      severity in WSP mice, whereas there was no effect of finasteride or EtOH
      injection on HICs in WSR mice. CONCLUSIONS: Collectively, these findings indicate
      that the WSP line is more sensitive than the WSR line to the modulatory effects
      of finasteride in terms of both chronic and acute EtOH withdrawal severity. The
      differential effect of finasteride on acute versus chronic EtOH withdrawal
      severity may result from an indirect effect of finasteride on EtOH
      pharmacokinetics in the chronic paradigm.

PMID- 15976520
TI  - Effects of melanocortin receptor activation and blockade on ethanol intake: a
      possible role for the melanocortin-4 receptor.
AB  - BACKGROUND: The melanocortin (MC) system is composed of peptides that are cleaved
      from the polypeptide precursor pro-opiomelanocortin. A growing body of literature
      suggests that the MC system modulates neurobiological responses to drugs of
      abuse. Because ethanol has direct effects on central pro-opiomelanocortin
      activity, it is possible that MC neuropeptides participate in the control of
      voluntary ethanol consumption. Here we assessed the possibility that MC receptor
      (MCR) agonists modulate ethanol intake via the MC3 receptor (MC3R) and/or the MC4
      receptor (MC4R) and whether the MCR antagonist AgRP-(83-132) controls ethanol
      consumption. METHODS: Mc3r-deficient (Mc3r) and wild-type (Mc3r) littermate mice
      were given intraperitoneal (10 mg/kg) and intracerebroventricular (1.0 microg
      ICV) doses of melanotan II (MTII), a nonselective MCR agonist. To assess the role
      of MC4R, C57BL/6J mice were given an ICV infusion of the highly selective MC4R
      agonist cyclo(NH-CH2-CH2-CO-His-d-Phe-Arg-Trp-Glu)-NH2 (1.0 or 3.0 microg).
      Finally, naive C57BL/6J mice were given an ICV infusion of AgRP-(83-132) (0.05
      and 1.0 microg). RESULTS: MTII was similarly effective at reducing ethanol
      drinking in Mc3r-deficient (Mc3r) and wild-type (Mc3r) littermate mice.
      Furthermore, ICV infusion of the MC4R agonist significantly reduced ethanol
      drinking, whereas ICV infusion of AgRP-(83-132) significantly increased ethanol
      drinking in C57BL/6J mice. Neither MTII nor AgRP-(83-132) altered blood ethanol
      levels at doses that modulated ethanol drinking. CONCLUSIONS: The present results
      suggest that MC4R, and not MC3R, modulates MCR agonist-induced reduction of
      ethanol consumption and that ethanol intake is increased by the antagonistic
      actions of AgRP-(83-132). These findings strengthen the argument that MCR
      signaling controls ethanol consumption and that compounds directed at MCR may
      represent promising targets for treating alcohol abuse disorders in addition to
      obesity.

PMID- 15976521
TI  - Central administration of melanin-concentrating hormone increases alcohol and
      sucrose/quinine intake in rats.
AB  - BACKGROUND: Alcohol is a caloric compound that can contribute to energy intake.
      Therefore, peptides that regulate energy balance likely modify the motivation to
      consume alcohol. Melanin-concentrating hormone (MCH) regulates energy homeostasis
      and has been implicated in other behaviors that impact alcohol consumption (i.e.,
      anxiety, fluid balance, and reward). We tested the hypothesis that MCH would
      decrease the motivation to consume alcohol secondarily to reducing anxiety.
      METHODS: Rats were trained to drink 10% ethanol or an isocaloric concentration of
      sucrose with use of a sucrose-fading technique. MCH (1, 5, or 10 microg) or its
      saline vehicle was administered into the third cerebral ventricle (i3vt), and
      intake of ethanol or sucrose and chow was assessed for 2 hr. Alcohol-naive rats
      were evaluated in an elevated plus maze after i3vt MCH (10 microg), neuropeptide
      Y, or saline administration. RESULTS: Contrary to the hypothesis, MCH dose
      dependently increased alcohol intake: saline = 0.7 +/- 0.1 g/kg, 1 microg MCH =
      1.0 +/- 0.1 g/kg, 5 microg MCH = 1.2 +/- 0.1 g/kg, and 10 microg MCH = 1.8 +/-
      0.3 g/kg (p < 0.01), and this was true whether water was simultaneously available
      or not. MCH also significantly increased sucrose intake (saline = 1.0 +/- 0.3
      g/kg, 10 mug MCH = 1.4 +/- 0.5 g/kg; p < 0.05). MCH had no effect on time spent
      in the open arms (54.3 +/- 11.5 sec) relative to saline (58.2 +/- 23.8 sec),
      whereas neuropeptide Y, a known anxiolytic, increased time spent on the open arms
      (119.2 +/- 22 sec, p < 0.05). CONCLUSIONS: We conclude that MCH nonspecifically
      increases ingestive behavior. Furthermore, MCH had no apparent effect on anxiety.
      The ability of MCH to increase alcohol and/or sucrose intake may be explained by
      the effect of MCH on energy balance and/or reward processes.

PMID- 15976522
TI  - Dopamine D(2) receptor availability is associated with subjective responses to
      alcohol.
AB  - BACKGROUND: The mesolimbic dopaminergic system is thought to mediate alcohol
      abuse and dependence. Determining the relationship between in vivo dopamine and
      the subjective response to alcohol could improve understanding of the mechanisms
      that lead to alcohol abuse and dependence. Here, we examined the relationship
      between dopamine D2 receptors in the nucleus accumbens and scores of perceived
      "high" and "intoxication" during an intravenous (IV) alcohol infusion. METHODS:
      Nine healthy control subjects received [C]raclopride PET scanning at baseline.
      Eight subjects received a second [C]raclopride scan during a pharmacodynamically
      modeled and controlled rise of IV alcohol, followed by steady state (60 mg% +/- 5
      mg%) alcohol infusion. Numerical ratings of "high" and "intoxication" were tested
      for correlations with measures of dopaminergic function. RESULTS: Baseline D2
      receptor availability in the left nucleus accumbens was significantly correlated
      with peak perceived "intoxication" (p = 0.02) and marginally correlated with peak
      perceived "high" (p = 0.07). CONCLUSIONS: Resting D2 receptor availability may
      predict healthy subject responses to alcohol exposure.

PMID- 15976523
TI  - Chronic ethanol consumption impairs learning and memory after cessation of
      ethanol.
AB  - Acute consumption of ethanol results in reversible changes in learning and memory
      whereas chronic ethanol consumption of six or more months produces permanent
      deficits and neural damage in rodents. The goal of the current paper was
      determine whether shorter durations of chronic ethanol ingestion in mice would
      produce long-term deficits in learning and memory after the cessation of ethanol.
      We first examined the effects of four and eight weeks of 20% ethanol followed by
      a three week withdrawal period on learning and memory in mice. We determined that
      three weeks after eight, but not four, weeks of 20% ethanol consumption resulted
      in deficits in learning and long-term memory (seven days) in T-maze footshock
      avoidance and Greek Cross brightness discrimination, step-down passive avoidance
      and shuttlebox active avoidance. Short-term memory (1 hr) was not affected. The
      deficit was not related to changes in thiamine status, caloric intake, or
      nonmnemonic factors, such as, activity or footshock sensitivity. Lastly, we
      examined if the mice recovered after longer durations of withdrawal. After eight
      weeks of ethanol, we compared mice after three and 12 weeks of withdrawal. Mice
      that had been off ethanol for both three and 12 weeks were impaired in T-maze
      footshock avoidance compared to the controls. The current results indicate that a
      duration of ethanol consumption as short as eight weeks produces deficits in
      learning and memory that are present 12 weeks after withdrawal.

PMID- 15976524
TI  - Does effect size in naltrexone trials for alcohol dependence differ for single
      site vs. multi-center studies?
AB  - BACKGROUND: The opioid antagonist naltrexone was first shown in single-site
      trials to be efficacious in the treatment of alcohol dependence. Recent clinical
      trials of the medication have used multi-center designs, which permit greater
      generalization and increased statistical power. We compared effect sizes for
      these two kinds of trial design on the hypothesis that multi-center trials
      introduce sources of variation that reduce the observed effect size. METHODS: A
      meta-analysis of data from 19 placebo-controlled trials of the efficacy of
      naltrexone (7 multi-center and 12 single-site studies) was performed. Effect size
      estimates for these two study designs were compared using two outcomes:
      percentage of days drinking and percentage of subjects relapsing to heavy
      drinking. RESULTS: Compared with single-site studies, multi-center studies were
      estimated to yield a nonsignificantly smaller effect on the percentage of days
      drinking (Cohen's d = 0.20 vs. 0.33, respectively) and a significantly smaller
      effect on the percentage of subjects relapsing to heavy drinking (Cohen's d =
      0.17 vs. 0.41, respectively; p = 0.014). Earlier studies showed a larger effect
      size than later studies. CONCLUSION: The smaller effect size seen with multi
      center studies may reflect random error due to heterogeneity among the sites.
      However, because multi-center studies were, in general, conducted more recently
      than single-site studies, it was not possible conclusively to disentangle the
      moderating impact of study type and year of publication on effect size. Further
      research on factors that moderate effect size can contribute to the development
      of medications to treat alcohol dependence.

PMID- 15976525
TI  - Hazardous drinkers and drug users in HMO primary care: prevalence, medical
      conditions, and costs.
AB  - BACKGROUND: There exists substantial evidence that individuals with alcohol and
      drug disorders have heightened comorbidities and health care costs. However,
      little is known about the larger population of "hazardous" drinkers (those whose
      consumption increases their "risk of physical and psychological harm") and drug
      users. METHODS: A sample of 1,419 patients from HMO primary care clinics was
      screened for hazardous drinking and drug use. Health plan databases were used to
      examine medical conditions and health care costs of hazardous drinkers and drug
      users in the year prior to screening, in comparison to 13,347 patients from the
      same clinics, excluding those screened. RESULTS: We found a prevalence of 7.5%
      for hazardous drinking and 3.2% for drug use in primary care (10% had at least
      one of the two problems). Hazardous drinkers and drug users had heightened
      prevalences for eight medical conditions, including costly conditions such as
      injury and hypertension, and psychiatric conditions. Medical costs for the year
      examined were not higher, except for those who also had psychiatric conditions.
      CONCLUSIONS: The prevalence of hazardous drinking and drug use was similar to
      hypertension and diabetes. Hazardous drinkers and drug users' heightened medical
      conditions, especially those related to alcohol and drug abuse, indicate that
      screening and brief intervention at this lower threshold of hazardous drinking
      and drug use will detect individuals with health risks sooner. Optimal treatment
      and prevention of some medical disorders may require identification and
      intervention of underlying hazardous alcohol or drug use.

PMID- 15976526
TI  - Ethanol-induced activation of myosin light chain kinase leads to dysfunction of
      tight junctions and blood-brain barrier compromise.
AB  - BACKGROUND: Brain endothelial cells form the blood-brain barrier (BBB) that
      regulates solute and macromolecule flux in and out of the brain, leukocyte
      migration, and maintains the homeostasis of the central nervous system. BBB
      dysfunction is associated with disruption of tight junctions (TJ) in the brain
      endothelium. We propose that alcohol abuse may impair BBB permeability through TJ
      modification. METHODS: Primary cultured bovine brain microvascular endothelial
      cells (BBMEC) were treated with 50 mM ethanol (EtOH), and monolayer tightness was
      assessed by measurement of transendothelial electrical resistance (TEER). Changes
      in TEER were correlated with alterations in TJ protein distribution [occludin,
      zonula occludens-1 (ZO-1), claudin-5] using immunofluorescence (IF). Expression
      of myosin light chain (MLC) kinase (MLCK), ZO-1, claudin-5, and phosphorylated
      MLC, occludin and claudin-5 were determined by immunoprecipitation and Western
      blot. EtOH-induced changes in monocyte migration across in vitro BBB constructs
      were also examined. RESULTS: EtOH induced a decrease in TEER of BBMEC monolayers
      that was reversed by EtOH withdrawal. Treatment of BBMEC with EtOH or its
      metabolite, acetaldehyde, prior to monocyte application resulted in a 2-fold
      increase in monocyte migration across the BBB. IF demonstrated decrease in
      claudin-5 staining, occludin translocation from cell borders to cytoplasm and gap
      formation in EtOH-treated BBMEC monolayer. These changes paralleled significant
      increase in phosphorylation of MLC, occludin and claudin-5. EtOH-treated BBMEC
      showed reduction of total occludin and claudin-5 without changes in ZO-1 or MLC.
      TEER decrease, changes in occludin/claudin staining, increase in MLC, occludin
      and claudin-5 phosphorylation and enhanced monocyte migration across the BBB were
      all reversed by inhibition of MLCK. Inhibition of EtOH metabolism in BBMEC also
      reversed these events. CONCLUSION: These results suggest that EtOH activates MLCK
      leading to phosphorylation of MLC, occludin and claudin-5. Cytoskeletal
      alterations (MLC) and TJ changes (occludin and claudin-5 phosphorylation) result
      in BBB impairment (decrease in TEER). TJ compromise is associated with increased
      monocyte migration across the BBB.

PMID- 15976527
TI  - Reinstatement of serum pregnanolone isomers and progesterone during alcohol
      detoxification therapy in premenopausal women.
AB  - BACKGROUND: Alcohol abuse is associated with menstrual irregularities related to
      the inhibition of progesterone secretion involved in regulation of the menstrual
      cycle. Reduced progesterone metabolites, including pregnanolone isomers (PIs),
      are efficient neuromodulators. The authors attempted to evaluate whether levels
      of PIs reflect impairment in progesterone biosynthesis in premenopausal women
      treated for alcohol addiction and whether alcohol detoxification therapy
      contributes to the restoration of their reproductive functions and psychosomatic
      stability by influencing steroid biosynthesis. METHODS: Serum allopregnanolone
      (3alpha-hydroxy-5alpha-pregnan-20-one; P3alpha5alpha), pregnanolone
      (P3alpha5beta), isopregnanolone (P3beta5alpha), epipregnanolone (P3beta5beta),
      progesterone, pregnanolone sulfate (PregS), pregnanolone, and estradiol were
      measured in 20 women during therapy (at start, three days, 14 days, one month,
      and four months) by gas chromatography-mass spectrometry or radioimmunoassay. The
      results were evaluated by a linear mixed model for longitudinal data, with stage
      of the treatment and subject as categorical factors, phase of the menstrual cycle
      as a time-varying covariate, and age of the subject as a covariate and by
      regression in individual stages of the menstrual cycle. RESULTS: During
      detoxification treatment, progesterone increased in the luteal phase.
      P3alpha5alpha, P3beta5alpha, and P3beta5beta rose in both phases of the menstrual
      cycle. DISCUSSION: Given the similar mechanism in the effects of alcohol and
      steroids in activating gamma-aminobutyric acid A receptors, the restoration of
      progesterone and PIs during therapy could be explained by an adaptation to
      increasing requests for gamma-aminobutyric acid A-receptor activating substances
      owing to the cessation of alcohol intake or by the regeneration of progesterone
      formation. In conclusion, the reinstatement of progesterone, P3alpha5alpha, and
      P3beta5beta serum levels demonstrates the favorable effect of detoxification
      therapy on both reproductive functions and the psychosomatic stability of
      premenopausal women treated for alcohol addiction.

PMID- 15976528
TI  - Increased lipopolysaccharide sensitivity in alcoholic fatty livers is independent
      of leptin deficiency and toll-like receptor 4 (TLR4) or TLR2 mRNA expression.
AB  - BACKGROUND: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show
      increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is
      recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to
      induce common downstream activation of nuclear factor (NF)-kappaB and pro
      inflammatory pathways that are activated in AFL and NAFL. METHODS: Serum alanine
      aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6
      levels; hepatic NF-kappaB activity; and expression of TLR2, TLR4, inducible
      nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated
      in lean and leptin-deficient ob/ob mice after LPS challenge in combination with
      acute or chronic alcohol feeding. RESULTS: Increased LPS sensitivity in AFL and
      NAFL was characterized by elevated serum TNF-alpha and IL-6 induction. However,
      there was no difference in TLR2 and TLR4 mRNA levels between lean and ob/ob
      livers at baseline and after acute or chronic alcohol treatment. LPS increased
      TLR2, but not TLR4, mRNA levels in all groups. Chronic alcohol feeding and LPS
      increased serum ALT and TNF-alpha levels in lean but not in ob/ob mice compared
      with pair-fed controls. Hepatic NF-kappaB activation was increased in both ob/ob
      and lean mice after chronic alcohol feeding compared with pair-fed controls.
      Expression of iNOS, an inducer of oxidative stress, and HO-1, a cytoprotective
      protein, were higher in ob/ob compared with lean mice after chronic alcohol
      feeding. However, LPS-induced HO-1, but not iNOS, expression was attenuated in
      ob/ob compared with lean mice. CONCLUSION: These results imply that the increased
      sensitivity of AFL to LPS occurs without up-regulation of TLR2 or TLR4 genes and
      may be related to an imbalance of pro-inflammatory/oxidative and cytoprotective
      mechanisms.

PMID- 15976529
TI  - Differential adaptations in GABAergic and glutamatergic systems during ethanol
      withdrawal in male and female rats.
AB  - BACKGROUND: There are significant and consistent sex differences in recovery from
      ethanol withdrawal in our animal model of ethanol dependence. We have also
      observed significant and varied sex differences in subunit protein levels of
      gamma-aminobutyric acid A (GABAA) and the N-metheyl-D-aspartate subtype of
      glutamate receptors occurring with ethanol dependence and withdrawal. Considering
      the major role of these two systems as targets of ethanol, we wanted to explore
      additional possible mechanisms underlying changes in GABAergic and glutamatergic
      responses after chronic ethanol exposure. Therefore, the objective of the present
      study was to examine GABAergic- and glutamatergic-associated proteins at three
      days of ethanol withdrawal, when female rats appear to have largely recovered but
      male rats still display robust signs of withdrawal. METHODS: Male and female rats
      were fed 6% ethanol in a nutritionally complete liquid diet for 14 days according
      to a pair-fed design; withdrawal was initiated by replacement of the diet with
      chow. At three days of withdrawal, the cerebral cortex and hippocampus were
      dissected for use in Western blot analysis. The paired design was maintained
      throughout all experimental procedures. RESULTS: At three days of ethanol
      withdrawal, we found region-specific and sex-selective alterations in levels of
      GAD (glutamic acid decarboxylase, GABA synthetic enzyme), GABA and glutamate
      transporters, and the synapse-associated proteins HSP70, PSD-95, and
      synaptophysin. There were also several significant differences in transporter
      function at this time that varied between males and females. CONCLUSIONS: Taken
      together, these findings show differential adaptations of GABAergic and
      glutamatergic neurotransmission between female and male rats that are associated
      with withdrawal recovery. This suggests that selective withdrawal-induced
      neuroadaptations in regulation of these systems' activities underlie, at least in
      part, sex differences in withdrawal recovery between male and female rats.

PMID- 15976530
TI  - Maternal alcohol abuse and neonatal infection.
AB  - BACKGROUND: Since chronic alcohol use suppresses the adult immune system, we
      tested the hypothesis that maternal alcohol ingestion increases the risk of
      infection in term newborns. METHODS: Analysis of a large case-control study of
      birth weight for gestational age was performed focusing on maternal alcohol
      ingestion and the development of infection in term newborns > or =36 weeks
      gestation. After delivery, mothers were asked about alcohol and tobacco use in
      the 3 months prior to conception, the 1st, 2nd, and 3rd trimester of pregnancy.
      RESULTS: Eight hundred and seventy-two singleton newborns (872) > or = 36 weeks
      gestation were identified for analysis. A total of 51 (5.8%) had newborn
      infections. Gestational age, sex, and small for gestational age (SGA) were
      similar in the newborns with and without infection (p = NS). Infants whose
      mothers reported alcohol use, excessive drinking or smoking in pregnancy were
      more likely to have a newborn diagnosed with an infection than were mothers who
      reported abstaining from alcohol or cigarettes (p < 0.05). When controlling for
      race and smoking, SGA infants whose mothers used any alcohol had a 2.5-fold
      increase risk of infection, while excessive alcohol use increased the risk 3-4
      fold. In a multivariable logistic regression analysis controlling for low
      maternal income, smoking, and SGA, excessive alcohol use during the 2 trimester
      increased the risk of newborn infection (OR 3.7 [1.1,12.8], p < 0.05).
      CONCLUSIONS: Excessive maternal alcohol use is associated with an increased risk
      of newborn infection in this patient sample. Increased awareness and further
      clinical investigations are warranted to address the detrimental effects of fetal
      alcohol exposure on the developing immune system.

PMID- 15976531
TI  - Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics.
AB  - BACKGROUND: Homocysteine (Hcy) is formed as an intermediary in methionine
      metabolism. Impairment of Hcy remethylation or transulfuration leads to
      hyperhomocysteinemia, which is considered as a risk factor for atherosclerotic
      vascular disease and stroke in chronic alcoholics. The aim of the study was to
      investigate the prevalence of hyperhomocysteinemia in chronic alcoholics and the
      influence of alcohol consumption, vitamin deficiencies and liver damage on the
      plasma levels of Hcy. METHODS: 228 chronic alcoholic patients consecutively
      admitted for detoxication, classified according to clinical and biochemical data
      in normal liver (n = 117), and in mild to moderate liver disease (n = 111), and
      49 healthy controls were studied. Blood levels of Hcy, vitamin B6, vitamin B12
      and folate were measured. RESULTS: Plasma Hcy was significantly higher in chronic
      alcoholics than in controls (9.66 +/- 8.1 vs. 6.93 +/- 2.33 mumol/liter, p <
      0.025). Furthermore, plasma Hcy levels were significantly higher in chronic
      alcoholics with liver injury (12.17 +/- 10.14 mumol/liter) than in those with
      normal liver and in controls (p < 0.001). The prevalence of hyperhomocysteinemia
      was also significantly higher in alcoholics with liver damage than in those with
      normal liver and in controls (29.7%, 5.1%, and 2%, respectively, p < 0.001).
      Serum folate values were lower in chronic alcoholics than in controls (4.7 +/-
      2.6 vs. 7.6 +/- 2.4 nmol/liter, p < 0.001). The lowest values of folate were
      found in alcoholics with liver disease, especially in those with
      hyperhomocysteinemia, with a negative correlation between the two parameters.
      CONCLUSIONS: Moderate hyperhomocysteinemia is common in chronic alcoholics,
      mainly in those with liver damage, suggesting that, although folate deficiencies
      may have a contributory role, liver impairment, through changes in methionine
      metabolism, is the most important mechanism for the elevated plasma Hcy found in
      these patients.

PMID- 15976532
TI  - Short-term memory impairment and reduced hippocampal c-Fos expression in an
      animal model of fetal alcohol syndrome.
AB  - BACKGROUND: Previous work in our laboratory has shown that exposure to ethanol
      during the brain growth spurt impairs spatial short-term memory in rats on the
      delayed matching-to-place (DMP) version of the Morris water maze. The objectives
      of this study were to ascertain whether this impairment could: 1) be prevented by
      increasing the length of encoding time and 2) be related to hippocampal c-Fos
      expression. METHODS: Using an artificial rearing model, male Long-Evans rats were
      fed 6.5 g/Kg/day of ethanol from postnatal days 6-9, with controls fed an
      isocaloric amount of maltose dextrin. As adults, rats in each treatment condition
      were trained and subsequently tested on either the DMP version of the Morris
      water maze, or on a random platform version (RAN) that incorporated the same
      performance requirements, but disallowed spatial learning. Brains were processed
      for c-Fos expression. RESULTS: Ethanol-exposed rats showed longer search trials
      during training and took longer to learn the DMP task. When the delay between
      search and recall trials was increased from 60 sec to 120 min, the performance of
      ethanol-exposed rats was impaired compared with that of controls after a 10 sec,
      but not after a 45 sec, encoding time. Brain c-Fos expression was increased in
      hippocampus, prefrontal cortex and visual cortex in rats trained on the DMP
      compared to the RAN task. Furthermore, in the DMP-trained rats, hippocampal c-Fos
      expression was lower in ethanol-exposed rats. CONCLUSIONS: These results suggest
      that the short-term memory impairment of ethanol-exposed rats 1) can be improved
      slightly by an increase in encoding time and 2) is related to a decrease in c-Fos
      expression in the hippocampus.

PMID- 15976534
TI  - The management of hydrosalpinges: tubal surgery or salpingectomy?
AB  - PURPOSE OF REVIEW: The clinical management of hydrosalpinges in infertile
      patients remains a contentious issue. This review aims to provide a critical
      analysis on the available treatments for hydrosalpinges, which have recently
      created a fierce debate between the promoters of salpingectomy and in-vitro
      fertilization and those who endorse tubal surgery. RECENT FINDINGS:
      Hydrosalpinges have a detrimental effect on the outcome of in-vitro fertilization
      yet their mechanism is still unclear. Salpingectomy prior to in-vitro
      fertilization restores the likelihood of a successful outcome in a well defined
      group of patients with ultrasound-visible hydrosalpinges. However, not every
      woman with large hydrosalpinges should undergo salpingectomy as some fallopian
      tubes may be amenable to surgical repair. Preserved tubal mucosa indicates a good
      prognosis for tubal surgery, therefore an appropriate mucosal assessment should
      be routine prior to deciding upon further management. SUMMARY: As salpingectomy
      is a definitive procedure it should be performed when the hydrosalpinges are
      beyond repair or in cases of in-vitro fertilization failure. Tubal surgery should
      be preferred to salpingectomy in mild to moderate tubal disease. A comparative
      study of restorative tubal surgery versus salpingectomy and in-vitro
      fertilization in selected women with hydrosalpinges is needed and will
      significantly help this debate. Prophylactic salpingectomy prior to in-vitro
      fertilization and tubal surgery is not competing but complementary in the
      treatment of hydrosalpinges-related infertility.

PMID- 15976535
TI  - The role of uterine artery embolization in the management of uterine fibroids.
AB  - PURPOSE OF REVIEW: Uterine artery embolization is increasingly being offered as
      an alternative to hysterectomy and myomectomy for the treatment of symptomatic
      uterine fibroids. This review is intended to evaluate the role of this technique
      in the management of uterine fibroids using information provided from recently
      published literature. RECENT FINDINGS: A growing body of literature supports the
      efficacy of uterine artery embolization in relieving fibroid-related menorrhagia,
      pelvic pain and pressure symptoms and in substantially reducing the fibroid size
      in most patients. Recent publications also show significant improvements in
      health-related quality of life and high long-term satisfaction rates. The
      procedure is associated with shorter hospitalization and recovery times and lower
      morbidity rates compared with conventional surgical treatments. However, serious
      complications, such as uterine infarction or infection leading to emergency
      hysterectomy, have been reported in a few cases, and considerable work is
      currently underway to determine how the safety of the procedure can be enhanced.
      Although no long-term data on subsequent fertility are yet available, early
      reports on ovarian function and pregnancy outcomes after uterine artery
      embolization are encouraging. SUMMARY: Based on current evidence, uterine artery
      embolization can be considered a valuable alternative to surgical therapy in the
      management of well-selected women with symptomatic uterine fibroids. Additional
      research is needed to help define the place of this technique for women who
      desire future pregnancy.

PMID- 15976536
TI  - The role of cryopreservation for women prior to treatment of malignancy.
AB  - PURPOSE OF REVIEW: The purpose of this review is to investigate recent advances
      in xenografting, as well as in orthotopic and heterotopic autotransplantation of
      human cryopreserved ovarian tissue. RECENT FINDINGS: The first livebirth after
      orthotopic transplantation of cryopreserved ovarian tissue was reported recently.
      We discuss this case and other cases of reimplantation of cryopreserved ovarian
      tissue, bearing in mind that many questions remain. SUMMARY: Finally, we report
      the latest developments in research on the transplantation of an intact ovary and
      the reimplantation of isolated follicles.

PMID- 15976537
TI  - Applications of intraoperative ultrasound in gynecological surgery.
AB  - PURPOSE OF REVIEW: Gynecologists are well trained in office-based ultrasound, but
      are less experienced in the field of intraoperative ultrasound. Many gynecologic
      procedures may benefit from the use of real-time ultrasonography. The purpose of
      this review is to summarize the current use of intraoperative ultrasound in
      gynecologic procedures. RECENT FINDINGS: Evaluation and assessment of the value
      of intraoperative ultrasound in gynecological procedures is essentially non
      existent. The role of intraoperative ultrasound in gynecology is in its infancy,
      with anecdotal experience and literature involving predominantly case reports.
      Intraoperative ultrasound is helpful in laparoscopic myomectomy, particularly
      when the uterine contour is normal. It is also useful in defining pelvic anatomy
      in cases of complex reproductive procedures. Intraoperative ultrasound improves
      precision in characterizing ovarian lesions, particularly in the setting of
      endometriomas or dermoid cysts. It has been shown to decrease both operative time
      and complication rates in dilation and curettage procedures. Intraoperative
      ultrasound reduces recurrence and re-operation rates after hysteroscopy by
      facilitating more-complete resection of uterine myomas. Ultrasound guidance
      improves the efficiency of embryo transfer in in-vitro fertilization and could
      potentially be beneficial in other 'blind' gynecological procedures. SUMMARY:
      Intraoperative ultrasound appears to be a safe and valuable tool for the
      gynecologic surgeon. Ultrasound improves visualization of anatomy, reduces
      complication and re-operation rates, and facilitates completion of more cases via
      less-invasive endoscopic approaches.

PMID- 15976538
TI  - Outcomes of laparoscopic treatment for endometrial cancer.
AB  - PURPOSE OF REVIEW: Laparoscopy has become the standard approach for the surgical
      management of a variety of benign gynecological conditions. Numerous studies have
      reported their findings on the laparoscopic approach for the treatment of
      patients with endometrial cancer. It is timely and relevant to provide a review
      of these findings. RECENT FINDINGS: Comparison analysis of recurrence and
      survival rates for patients treated by laparoscopy and laparotomy have found
      similar results. A similar or reduced cost is noted for the laparoscopic
      approach. Numerous patient advantages are indicated for the laparoscopic
      approach. This information is detailed in this review. SUMMARY: The open
      abdominal approach is an alternative to laparoscopy for the surgical treatment of
      patients with early endometrial cancer.

PMID- 15976539
TI  - An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin
      therapy for women with clomiphene citrate-resistant polycystic ovarian syndrome.
AB  - PURPOSE OF REVIEW: Women with polycystic ovarian syndrome are typically
      anovulatory and require ovulation induction. Ovarian wedge resection was the
      first treatment for anovulation but was eventually abandoned because of the
      increased risk of postsurgical adhesions and as medical ovulation induction with
      clomiphene and gonadotrophins was introduced. However, with the advent of
      laparoscopy, there has been a return to surgical approaches. The potential
      advantages of laparoscopic surgery include avoidance of hyperstimulation and the
      lowered costs make ovarian surgery an attractive alternative to gonadotrophins.
      RECENT FINDINGS: Clinical trials in New Zealand and the Netherlands have compared
      costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of
      treatment in the Netherlands study for the ovarian drilling group was euro 4664
      and for the gonadotrophins group was euro 5418. Without the cost of monitoring
      and the diagnostic laparoscopy then the difference was euro 2110 in favour of
      ovarian drilling. It was estimated that the cost per term pregnancy would be euro
      14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The
      higher rates of multiple pregnancy in the gonadotrophin group were considered to
      be responsible for the increased costs. In the New Zealand trial the costs of a
      live birth were one-third lower in the group that underwent laparoscopic ovarian
      diathermy compared with those women who received gonadotrophins (NZ$19,640 and
      29,836, respectively). SUMMARY: Treating women with clomiphene-resistant
      polycystic ovarian syndrome with laparoscopic ovarian diathermy results in
      reduced direct and indirect costs. The reduction in multiple pregnancies makes
      the alternative of surgery particularly attractive.

PMID- 15976540
TI  - Laparoscopic treatment of early ovarian cancer.
AB  - PURPOSE OF REVIEW: Recently some studies have reinforced the arguments supporting
      the laparoscopic management of early ovarian cancer. These studies and reports
      questioning the use of laparoscopy in patients with early ovarian cancer will be
      reviewed. RECENT FINDINGS: Advances in laparoscopic techniques have enabled the
      surgeon to meet the staging criteria for early ovarian cancer as proposed by the
      International Federation of Gynecology and Obstetrics (FIGO) guidelines. Although
      some reports highlight the risk of ovarian cancer mismanagement, the safety and
      reliability of laparoscopic surgical staging has been demonstrated with
      encouraging results. However, the numbers of patients included in these studies
      are still insufficient to draw conclusions. SUMMARY: Clinical evidence supports
      the use of laparoscopy in the treatment or completion of treatment in patients
      diagnosed with early ovarian cancer. If strict guidelines are respected, tumor
      rupture, dissemination and implant on the trocar insertion sites can be avoided
      and survival outcomes appear not to be jeopardized. Inadequate and hazardous
      laparoscopic management of early ovarian cancer is to be ascribed to the lack of
      guidelines and to surgeons without the competence to treat early ovarian cancer
      rather than to the surgical technique. The excellent outcomes could encourage
      studies with larger sample sizes to confirm the validity of laparoscopic
      treatment of patients with early ovarian cancer. Unfortunately, a clinical trial
      is unlikely to be undertaken due to the low incidence of this disease and the
      even lower number of events.

PMID- 15976541
TI  - The role of the levonorgestrel-releasing intrauterine device in the management of
      symptomatic endometriosis.
AB  - PURPOSE OF REVIEW: The aim of this article is to evaluate the biological
      rationale for the use of an intrauterine device releasing 20 mug/day of
      levonorgestrel in women with endometriosis, and to assess its efficacy in
      relieving pelvic pain symptoms. RECENT FINDINGS: Levonorgestrel induces
      endometrial glandular atrophy and extensive decidual transformation of the
      stroma, downregulates endometrial cell proliferation, increases apoptotic
      activity, and has antiinflammatory and immunomodulatory effects. Up to 85% of
      patients wearing the device have anovulatory cycles during the first 3 months of
      use, but the proportion falls to below 35% by 12 months. After the first year of
      use, a 70-90% reduction in monthly blood loss is observed; few women report
      intermenstrual bleeding and about 20-30% amenorrhea. This is advantageous in
      patients experiencing dysmenorrhea. Although it is maintained that the hormonal
      activity of the levonorgestrel intrauterine device is local, a systemic effect
      secondary to uterine absorption of levonorgestrel is probable. The levonorgestrel
      intrauterine device has proven effective in relieving pelvic pain symptoms caused
      by peritoneal and rectovaginal endometriosis and in reducing the risk of
      recurrence of dysmenorrhea after conservative surgery. SUMMARY: Intrauterine
      administration of levonorgestrel with direct distribution to pelvic tissues would
      imply a local concentration greater than plasma levels. This could result in a
      superior effectiveness with limited adverse effects and increased patient
      compliance during long-term treatment. Further trials are needed, however, to
      verify whether the good results observed are maintained during an entire 5-year
      period, to confirm the efficacy on dyspareunia and dyschezia, and to compare the
      effects of the levonorgestrel intrauterine device with those of other treatment
      options.

PMID- 15976542
TI  - Hysteroscopy and menopause: past and future.
AB  - PURPOSE OF REVIEW: The main aim in investigating post-menopausal women is to
      exclude endometrial cancer. The purpose of this review is to define up-to-date
      clinical guidelines for the management of all post-menopausal women (asymptomatic
      as well as symptomatic). RECENT FINDINGS: Thanks to improvements in both the
      technology and the technique, hysteroscopy has become a simple and painless
      procedure that can easily be performed in an office or outpatient setting without
      any particular discomfort for the patient. The new, easier procedure, well
      tolerated by patients, has excellent diagnostic and surgical accuracy. Assuming
      that office hysteroscopy could offer a better visualization of the uterine cavity
      without increasing patient discomfort if compared to ultrasound, various authors
      have recently proposed the use of hysteroscopy as a first-line procedure in the
      approach to the menopausal patient. This could be defined as a change in strategy
      that has yielded very interesting results in terms of a better understanding of
      the appearance of the uterine cavity and the clinical value of small intra
      cavitary pathologies (and their related treatment), particularly in asymptomatic
      women. SUMMARY: Hysteroscopy can be considered a routine outpatient method
      providing immediate results and causing minimal discomfort, especially when
      performed with the vaginoscopic approach. This technique has ushered in a new era
      of very-low-cost hysteroscopy, because only the hysteroscope is required in the
      outpatient procedure, with no need for additional instruments, medication, extra
      personnel or dedicated theatre. The time taken is comparable to that required for
      transvaginal sonography.

PMID- 15976543
TI  - The use of laparoscopic sacrocolpopexy in the management of pelvic organ
      prolapse.
AB  - PURPOSE OF REVIEW: This paper aims to review and comment on the developments in
      laparoscopic sacrocolpopexy published during the last year. RECENT FINDINGS: We
      classified the findings reported recently in the literature for laparoscopic
      sacrocolpopexy as technical or tactical findings. Technical findings concern the
      material of the mesh, the methods of mesh fixation, the use of adapted vaginal
      retractors and the interest in robotic assistance. Tactical findings consist of
      specific modifications to the standard surgical procedure aimed at reducing the
      side effects and complications and ameliorating the effectiveness of this
      intervention. These modifications include the possibility of avoiding the
      placement of a posterior mesh and the fixation of the posterior mesh to the
      puborectal muscles or the perineal body instead of the posterior vaginal wall. A
      specific section has been dedicated to reviewing and commenting on those
      interventions associated routinely with laparoscopic sacrocolpopexy. SUMMARY:
      Laparoscopic sacrocolpopexy is a safe surgical procedure in constant evolution
      which allows excellent results in the treatment of utero-vaginal prolapse. Large
      prospective, randomized studies comparing the different technical and tactical
      modifications recently introduced are needed in order to further enhance the
      effectiveness of this intervention.

PMID- 15976544
TI  - Endometrial ablation for heavy menstrual bleeding.
AB  - PURPOSE OF REVIEW: This review evaluates the currently available evidence
      regarding resectoscopic endometrial ablation (REA) and the various
      nonresectoscopic endometrial ablation (NREA) techniques used for heavy menstrual
      bleeding. RECENT FINDINGS: Laser endometrial ablation is now used infrequently,
      largely because of procedure time, but also because of the cost and training
      associated with the technique. REA can be performed in a wider spectrum of
      endometrial cavity configurations than NREA and, at least in expert hands,
      remains the gold standard. Each of the five available types of NREA device
      possesses advantages and disadvantages over the others with respect to variables
      such as treatment time, required cervical dilation, and size and configuration of
      the endometrial cavity. All provide acceptable results that are comparable to
      that of REA in expert hands. Serious complications seem to be less common with
      NREA, but uterine perforation and bowel or other visceral injury can still occur.
      When endometrial-ablation patients were followed for up to 5 years, repeat
      surgery rates ranged from 20 to 40%, thereby eroding both the direct and indirect
      treatment-related resource utilization. Levonorgestrel-releasing intrauterine
      devices demonstrate similar clinical and patient-satisfaction outcomes to
      endometrial ablation but can be inserted in the office and allow maintenance of
      fertility. SUMMARY: Both REA and NREA provide at least short- to intermediate
      term options to hysterectomy for patients with heavy menstrual bleeding and
      normal or near-normal endometrial cavities. Consequently, the ideal candidates
      are likely those who are within 5 years of menopause.

PMID- 15976545
TI  - Adhesion prevention in gynecologic surgery.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss new substances and
      techniques to prevent post-surgical adhesion formation. RECENT FINDINGS:
      Intraperitoneal administration of sprayable hydrogel and hyaluronic acid appears
      to decrease postmyomectomy adhesions. Intrauterine instillation of auto
      crosslinked hyaluronic acid is associated with fewer intrauterine adhesions.
      Temporary abdominal oophoropexy after surgery of stage III and IV endometriosis
      might be beneficial in reducing ovarian adhesion. SUMMARY: There has been a wide
      range of adhesion-reducing substances evaluated in animal models. However, in
      clinical situations, no adhesion-preventing substance, material, or barrier is
      unequivocally effective. In view of surgical technique, compared to laparotomy,
      the laparoscopic approach is associated with less adhesion formation. Temporary
      abdominal oophoropexy may provide a promising technique to prevent ovarian
      adhesions. Future research should also be directed toward preventing intrauterine
      adhesions.

PMID- 15976546
TI  - Outcomes and treatment options in rectovaginal endometriosis.
AB  - PURPOSE OF REVIEW: This review aims to explore the recent literature surrounding
      the role of colorectal surgery in rectovaginal endometriosis. RECENT FINDINGS:
      Recent findings would suggest that excision of a portion of the rectum along with
      complete excision of surrounding endometriosis is beneficial in terms of
      improvement in quality of life and recurrence of disease. However, further
      randomized controlled trials are needed to clarify this finding. SUMMARY: The
      optimal management of women with deeply infiltrating rectovaginal endometriosis
      remains a challenge to physicians involved in this disease process. The choice
      between medical and surgical treatments is not clearly defined, and neither is
      the role of adjunctive medical therapy prior to or following surgery. It is only
      when these questions have been asked in the context of well conducted clinical
      trials, with good outcome data, can the answers be given.

PMID- 15976547
TI  - Managing disorders of ovulation: a model for evidence-based practice.

PMID- 15976548
TI  - Predictive values of ultrasound monitoring of the menstrual cycle.
AB  - PURPOSE OF REVIEW: This review summarizes the current knowledge about ultrasound
      scanning values in monitoring the structural and functional changes of the uterus
      and ovaries during the menstrual cycle. RECENT FINDINGS: The views that ovulation
      is more frequently right sided have been challenged, with recent data suggesting
      that ovulation occurs randomly. A 'follicular wave phenomenon', providing a new
      model for ovarian function during the menstrual cycle, has been described.
      Follicular development occurs in a wave-like fashion and women with two waves
      have earlier endometrial development due to earlier increase of the dominant
      follicle estrogen production. Myometrial contractions during menstrual cycle
      should be considered in the assessment of endometrial thickness. Uterine-ovarian
      arterial blood flow impedance is important in understanding the normal physiology
      of the menstrual cycle and may be of use in assisted conception protocols.
      SUMMARY: At present, ultrasound scanning has an important role in noninvasive
      assessment of endometrial and ovarian cyclical changes and may be of particular
      importance in assisted conception procedures. Further work is likely to help in
      understanding its full diagnostic potential.

PMID- 15976549
TI  - Menorrhagia, mechanisms and targeted therapies.
AB  - PURPOSE OF REVIEW: Efficient treatment options for the increasing complaint of
      heavy menstrual bleeding are required to avoid the morbidity associated with
      major surgery. This review summarizes recent developments in the nonsurgical
      approach to treating menorrhagia. RECENT FINDINGS: Even though the mechanism of
      menstruation has still not been fully elucidated, there have been promising
      developments in the attempt to reduce menstrual blood loss. The levonorgestrel
      releasing intrauterine system has proven very efficient, and there is a frameless
      device suitable for enlarged uterine cavities. The side effect of breakthrough
      bleeding has been the main reason for discontinuing treatment. Recent studies
      have investigated options of concomitant therapy with antiprogestogens to counter
      this effect. Another group of novel compounds are selective progesterone receptor
      modulators, which thus far have been shown to reduce menstrual bleeding without
      the unwanted effect of unscheduled bleeding episodes. SUMMARY: As menorrhagia is
      largely a subjective complaint, it is important for successful therapy to be
      based on an informed patient's choice. Currently, lack of evidence-based
      practice, poor compliance and unpleasant side effects limit the success of
      medical therapies contributing to the amount of major surgery performed for this
      indication. If concomitant therapies succeeded in minimizing the episodes of
      breakthrough bleeding with the levonorgestrel-releasing intrauterine system, its
      recommendation as a first choice treatment may be confounded. Further research is
      needed into efficiency and safety of selective progesterone receptor modulators,
      which appear to have great potential in reducing menstrual blood loss.

PMID- 15976550
TI  - Vascular endothelial growth factor expression in the endometrium during the
      menstrual cycle, implantation window and early pregnancy.
AB  - PURPOSE OF REVIEW: The review aims to summarize recent data about vascular
      endothelial growth factor and its implications in the normal endometrium during
      the menstrual cycle, implantation window and early pregnancy. RECENT FINDINGS:
      Angiogenesis is crucial for the development of endometrium as well as for embryo
      implantation and establishment of pregnancy. A number of cytokines and growth
      factors including vascular endothelial growth factor are known to modulate
      angiogenesis in human endometrium in vitro and in vivo. Intrauterine vascular
      endothelial growth factor expression has been shown to be regulated in a cycle
      dependent fashion. Recent studies have demonstrated that female sex steroid
      hormones and gonadotrophins contribute to the regulation of vascular endothelial
      growth factor by endometrial glandular epithelial and stromal cells. Vascular
      endothelial growth factor levels increase around the peri-implantation period and
      in the late secretory and pre-menstrual phases. Further, the production of this
      angiogenic growth factor appears to be related to decidualization. SUMMARY:
      Vascular endothelial growth factor is a key regulator of angiogenesis and
      vascular function in the human endometrium. Aberrant endometrial angiogenesis may
      result in menstrual dysfunction, failed implantation and first-trimester
      miscarriage. The possibility of enhancing or inhibiting angiogenic activity in
      the endometrium will provide a novel approach to the manipulation of reproductive
      functions.

PMID- 15976551
TI  - The endocrinological basis of recurrent miscarriages.
AB  - PURPOSE OF REVIEW: This review discusses the endocrinological aspects of
      recurrent miscarriage based on the literature from January 2004 to January 2005,
      elaborating on the advances in the field and their impact on diagnosis and
      management. RECENT FINDINGS: Endometrial luteal phase defect is associated with
      recurrent miscarriage. Fifty years have passed since the diagnostic criteria for
      dating the endometrial biopsy was established by Noyes et al. This has been the
      gold standard and last year its accuracy and clinical utility were critically
      analysed. A Cochrane review has shown a small but statistically significant
      difference in the live birth rate in the subgroup of women in which progestogen
      was used to prevent recurrent miscarriage. Endocannabinoids and fatty acid amide
      hydrolase have been found to have a potential role in signalling for implantation
      and maintenance of pregnancy. SUMMARY: Abnormal secretory endometrial changes may
      adversely affect the early pregnancy outcome. Other dating techniques using
      biochemical and molecular markers of endometrial function may prove useful in
      predicting outcome. Use of progestogens with or without estrogens for prevention
      of recurrent miscarriage needs to be investigated further in larger randomized
      controlled trials. The role of endocannabinoids and agents modulating their
      receptors are potentially very exciting areas to be explored further.

PMID- 15976552
TI  - Selective oestrogen receptor modulators, aromatase inhibitors and the female
      breast.
AB  - PURPOSE OF REVIEW: Tamoxifen has been available for over 20 years and remains the
      most commonly recognized endocrine therapy. This review was prompted by a wealth
      of new data on several newer endocrine agents, including selective oestrogen
      receptor modulators, aromatase inhibitors and a new oestrogen receptor
      antagonist, fulvestrant, which unlike the selective oestrogen receptor modulators
      has no oestrogen agonist effects. RECENT FINDINGS: Completed analysis of the
      'Arimidex', Tamoxifen, Alone or in Combination trial demonstrated that
      anastrozole as initial adjuvant therapy significantly improved disease-free
      survival and time to recurrence compared with tamoxifen, as well as reducing the
      incidence of contralateral breast cancer deaths. The Italian Tamoxifen
      Anastrozole trial and the Austrian Breast and Colorectal Cancer Study Group
      8/Arimidex Nolvadex 95 trial have indicated that anastrozole may also be
      beneficial in women who have already received 2-3 years of tamoxifen. Similarly,
      the Intergroup Exemestane Study demonstrated the efficacy of exemestane in this
      setting. Women who have completed a full 5-year course of tamoxifen may also
      benefit from aromatase inhibitor treatment as indicated by the MA 17 trial, which
      investigated letrozole as extended adjuvant therapy. Fulvestrant is effective in
      tamoxifen-resistant disease, and phase II trial data suggest that fulvestrant may
      also be effective following aromatase inhibitor failure. SUMMARY: The
      introduction of the third-generation aromatase inhibitors has caused a paradigm
      shift in adjuvant endocrine treatment. Research into the optimal use of selective
      oestrogen receptor modulators continues and the evidence base for fulvestrant,
      the first in a new class of endocrine agents, continues to grow, confirming its
      value in the treatment of hormone-responsive breast cancer.

PMID- 15976553
TI  - Bone status during adolescence, pregnancy and lactation.
AB  - PURPOSE OF REVIEW: At birth, the fetus will contain 30 g of calcium; during the
      third trimester the calcium accrual can be up to 340 mg/day. Therefore, extremely
      high demands for calcium provision are placed upon the mother. This review aims
      to describe the adaptive mechanisms of the female skeleton to pregnancy and
      lactation, which ensure optimal fetal skeletal mineralization without compromise
      to maternal bone strength. RECENT FINDINGS: Descriptions of changes in bone
      status during pregnancy and lactation have been published. One of the only
      studies to measure pre-conception to post-weaning shows complete recovery of
      maternal spinal bone mineral density (BMD) and near recovery at the hip. Most
      studies describe trabecular bone loss, but there is evidence for endosteal
      resorption of the metacarpals. In a retrospective study of former teenage mothers
      those who breastfed had similar hip BMD to nulliparous age-matched women; those
      who did not breastfeed had lower hip BMD. Maternal response to low calcium intake
      differs from that of normal calcium intake. SUMMARY: Pregnancy and lactation do
      not have an overall negative effect upon the maternal skeleton. Retrospective
      evidence suggests no harmful effect of teenage pregnancy if the teenager
      breastfed, but this requires further investigation. The effects of other
      situations, for example low vitamin D status or low calcium intake, require
      further research to inform future clinical practice.

PMID- 15976554
TI  - Bibliography. Current world literature. Minimally invasive gynecologic
      procedures.

PMID- 15976555
TI  - Factors influencing the development of a hepatitis C exercise protocol: a
      literature review.
AB  - Chronic hepatitis C (HCV) varies greatly in its course and outcomes. Reports of
      fatigue and other symptoms are common during treatment and when patients are not
      receiving treatment. Exercise as a form of treatment for HCV-related fatigue has
      had little attention in research studies, yet data from studies in closely
      related chronic conditions consistently report the value of exercise for
      maintaining and improving health and reducing risk factors. This article examines
      the factors influencing the development of an exercise protocol as an adjunct to
      health promotion in patents with HCV. A review of the current literature
      summarizes findings from the areas of exercise in chronic illness states,
      exercise measures, and exercise prescription as treatment for chronic illnesses,
      with a focus on HCV. Nurses should consider these factors when developing an
      exercise protocol as an alternative treatment for side effects and symptoms
      related to hepatitis C and other chronic conditions. More research on specific
      exercise prescriptions should be undertaken and reported in the literature.

PMID- 15976556
TI  - Hepatitis C: are you confused?: Issues related to patient education.
AB  - More than 4 million Americans are infected with the hepatitis C virus. Although
      overshadowed by acquired immune deficiency syndrome, the hepatitis C epidemic is
      now recognized as a major health problem. Prevalence is estimated to be anywhere
      from 1.2% to 10% in specific populations. Nurses continue to express confusion in
      understanding the disease process; therefore, many opportunities are missed to
      counsel patients and families who may be at risk or who have hepatitis C. Many
      patient questions go unanswered because nurses mistakenly assume the medical
      provider will educate these patients and families. However, nurses have more
      contact with patients, and one of the nurse's roles is to provide health
      education. The Society of Gastroenterology Nurses and Associates and the Joint
      Commission on Accreditation of Healthcare Organizations agree it is the nurse's
      role to educate patients. Accurate hepatitis C virus information helps nurses
      guide patients and families in understanding this disease process.

PMID- 15976557
TI  - Assessment of the patient who failed treatment for chronic hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection affects more than 4 million people in
      the United States and 170 million people in the world, making it a major public
      health problem. Currently, about one half of the patients undergoing hepatitis C
      treatment do not experience a sustained viral response. With time, this high
      nonresponse rate has created a large pool of such patients (nonresponders), many
      of whom have advanced fibrosis or cirrhosis. Patients who are selected for re
      treatment need healthcare providers with experience, knowledge, and the time
      available to manage the side effects to maximize adherence to therapy. This
      article discusses the assessment of patients being re-treated for HCV and
      approaches to caring for this patient population.

PMID- 15976560
TI  - The role of hepatitis C support groups.
AB  - Chronic hepatitis C infection has become the most common blood-borne pathogen in
      the United States, affecting an estimated 4 million Americans. The diagnosis of
      chronic hepatitis C carries with it threats to quality of life and life
      expectancy. Furthermore, the label of chronic hepatitis C encumbers the
      individual with concerns about contagiousness, social isolation, altered role
      function, stigmatization, loss of control, and the uncertainty and anxiety
      inherent in any chronic illness. These factors have a significant emotional
      effect on the affected individual and his or her family. Although biomedical
      research continues to seek new therapies for hepatitic C virus and methods of
      prevention and control, our health and social systems also must develop
      strategies to facilitate adjustment, provide education and caring, and enhance
      well-being. Abundant research supports the premise that social support
      facilitates patient well-being and contributes to health and health promotion
      through interpersonal interactions. Gastroenterology nurses are well positioned
      to facilitate improved outcomes in patients with chronic hepatitis C virus by
      initiating interventions designed to enhance existing sources of social support
      or to promote new ones. Development of psychosocial interventions, such as
      support groups, aimed at maintaining or fostering social support, may improve
      health outcomes and promote a higher health-related quality of life for persons
      living with chronic hepatitis C virus.

PMID- 15976562
TI  - Schistosomiasis: implications for world travelers and healthcare providers.
AB  - Schistosomiasis ranks second, behind malaria, among human parasitic diseases in
      terms of public health and socioeconomic importance in tropical and sub-tropical
      areas. Worldwide, 1 of 30 people has schistosomiasis. Up to 300 million people
      are infected, and 600 million live in environments where infection is a risk.
      Tourists from non-endemic areas are contracting schistosomiasis due to the rise
      in "off-the-beaten-track" tourism. Praziquantel is effective against all species
      of schistosomes and early treatment is curative. Schistosomiasis is an insidious
      disease, however, so worldwide the disease is not diagnosed early. The most
      frequent and dangerous complication of the disease is variceal hemorrhage due to
      hepatic fibrosis. Variceal hemorrhage is the first symptom in 58% of cases. A
      variety of treatments for variceal hemorrhage are available. Exsanguination from
      variceal hemorrhage is possible; therefore, aggressive stabilization of the
      patient by the use of multiple therapies is appropriate. Most patients treated
      after esophageal hemorrhages do not experience reversal of hepatic fibrosis. For
      this reason, healthcare providers need an increased awareness of schistosomiasis
      to enable earlier detection and treatment in world travelers.

PMID- 15976564
TI  - Implementing "lean" principles to improve the efficiency of the endoscopy
      department of a community hospital: a case study.
AB  - Many endoscopy units are looking for ways to improve their efficiency without
      increasing the number of staff, purchasing additional equipment, or making the
      patients feel as if they have been rushed through the care process. To accomplish
      this, a few hospitals have looked to other industries for help. Recently, "lean"
      methods and tools from the manufacturing industry, have been applied successfully
      in health care systems, and have proven to be an effective way to eliminate waste
      and redundancy in workplace processes. The "lean" method and tools in service
      organizations focuses on providing the most efficient and effective flow of
      service and products. This article will describe the journey of one endoscopy
      department within a community hospital to illustrate application of "lean"
      methods and tools and results.

PMID- 15976565
TI  - Comparison of quality of life of persons who have experienced amputations and
      persons who have had bowel resections.
AB  - Comparing the quality of life of persons who have experienced amputations and
      persons who have had bowel resections illustrates the impact of chronic disease
      upon all aspects of a patient's life. Because the purpose of nursing research is
      to bring about knowledge to better direct patient care, understanding the impact
      of chronic illness contributes to an improvement in the quality of life of these
      patients. By appreciating the patient's perspective concerning the illness, the
      nurse can better educate the patient in all aspects of the disease process. Based
      on Jean Watson's Theory of Human Caring, this study acknowledged the need for
      evidence-based nursing practice to care for the well-being of the patient in a
      holistic manner. Our hypothesis was adult patients after Crohn disease-related
      bowel resection experience a better quality of life than do adult patients with
      peripheral vascular disease related amputation. This descriptive comparative
      study had a sample of patients with Crohn disease and resection (n = 28) and
      patients with peripheral vascular amputation (n = 16). The instrument used to
      measure quality of life was the RAND-36 Item Health Survey 1.0. Results revealed
      significant differences between the patients with bowel resection and those with
      peripheral vascular amputation with regard to physical functioning, general
      health, and role limitations related to physical health. No significant
      differences existed between the two groups in terms of energy/fatigue, emotional
      well-being, social functioning, role limitations related to emotional problems,
      and pain. Results from the data may indicate that the incorporation of more
      education regarding social, emotional, physiological, and psychological aspects
      of postoperative life may be of importance to evidence based nursing practice.
      This addition may also lead to better adjustment to postoperative life for
      patients and improve overall quality of life.

PMID- 15976566
TI  - A survey of role diversity among advanced practice nurses in pediatric
      gastroenterology.
AB  - A survey of advanced practice nurses in the Association of Pediatric
      Gastroenterology and Nutrition Nurses (APGNN) was conducted to assess role
      diversity in anticipation of sharing these results with our international
      colleagues at the World Congress in 2004. A single-page, 14-item survey was sent
      via e-mail or fax to 79 APGNN advanced practice nurses identified by their
      credentials (MS, PNP, FNP) in the membership database. Forty surveys were
      returned via e-mail or fax for an overall response rate of 51%. Most reported
      working full time as nurse practitioners in an outpatient gastrointestinal
      clinic, yet almost one third were hospital based. Additional job titles included
      clinical nurse specialist, researcher, and case manager or clinical coordinator.
      Slightly more than one half reported seeing any patients in their outpatient
      practice, whereas 43% saw specific populations, with constipation,
      gastroesophageal reflux, and abdominal pain being the most common diagnoses.
      Seventy percent had prescriptive privileges. Billing practices were the most
      diverse, with 30% always billing under their own number, 23% sometimes billing
      under their own number, and 40% never billing under their own number (5% not
      applicable). Overall, most advanced practice nurses in APGNN are pediatric nurse
      practitioners with a primary focus on outpatient care but also are involved in
      patient and family teaching, nutrition support, home care, and research. Only a
      few were involved with procedures, which may be surprising to our adult
      counterparts.

PMID- 15976567
TI  - The importance of abdominal pressure during colonoscopy: techniques to assist the
      physician and to minimize injury to the patient and assistant.
AB  - This article outlines techniques that can be used to assist the physician's
      ability during colonoscopy to achieve cecal intubation in both standard
      situations and in specific conditions such as the obese patient. When applied
      properly, abdominal pressure can help shorten the length of the procedure,
      minimize the angle of turns in the colon, and minimize discomfort to the patient.
      A Mayo physician survey unanimously concluded that abdominal pressure is
      beneficial during colonoscopy. This article addresses the ergonomics of applying
      pressure and suggests techniques that minimize risk of injury to both the patient
      and the assistant. In addition, questions that new assistants may ask are
      addressed.

PMID- 15976569
TI  - Cautery and implanted cardiac defibrillators.

PMID- 15976570
TI  - Endoscopic staging.

PMID- 15976571
TI  - Why ethics and gastroenterology nursing?

PMID- 15976572
TI  - On castle building.

PMID- 15976573
TI  - Spiritual care research.

PMID- 15976574
TI  - Pain and cramping with enema administration.

PMID- 15976575
TI  - Endoscopy storage: preventing distal tip protector contamination.

PMID- 15976580
TI  - Adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to silicone
      hydrogel contact lenses.
AB  - PURPOSE: The purpose of this study is to compare the adhesion capabilities of the
      most important etiologic agents of microbial ocular infection to the recently
      available silicone-hydrogel lenses with those to a conventional hydrogel lens.
      METHODS: In vitro static adhesion assays of Pseudomonas aeruginosa 10,145,
      Staphylococcus epidermidis 9142 (biofilm-positive), and 12,228 (biofilm-negative)
      to two extended-wear silicone-hydrogel lenses (balafilcon A and lotrafilcon A), a
      daily wear silicone-hydrogel lens (galyfilcon A) and a conventional hydrogel
      (etafilcon A) were performed. To interpret the adhesion results, lens surface
      relative hydrophobicity was assessed by water contact angle measurements.
      RESULTS: P. aeruginosa and S. epidermidis 9142 exhibited greater adhesion
      capabilities to the extended wear silicone-hydrogel lenses than to the daily wear
      silicone- and conventional hydrogel lenses (p < 0.05). No statistical differences
      were found between the adhesion extent of these strains to galyfilcon A and
      etafilcon A. The biofilm negative strain of S. epidermidis adhered in larger
      extents to the silicone-hydrogel lenses than to the conventional hydrogel (p <
      0.05), but in much lower amounts than the biofilm-positive strain. The water
      contact angle measurements revealed that the extended wear silicone-hydrogel
      lenses are hydrophobic, whereas the daily wear silicone- and conventional
      hydrogel lenses are hydrophilic. CONCLUSIONS: As a result of their
      hydrophobicity, the extended wear silicone-hydrogel lenses (lotrafilcon A and
      balafilcon A) may carry higher risk of microbial contamination than both the
      hydrophilic daily wear silicone-hydrogel lens, galyfilcon A and the conventional
      hydrogel lens, etafilcon A.

PMID- 15976581
TI  - Microbial flora of tears of orthokeratology patients, and microbial contamination
      of contact lenses and contact lens accessories.
AB  - PURPOSE: The purpose of this study is to determine if there are changes in the
      ocular flora of overnight orthokeratology (ortho-k) patients, and the levels of
      contamination of their lenses and lens accessories, and to correlate compliance
      with levels of contamination. METHOD: Normal ocular flora of 41 subjects was
      determined twice before commencing ortho-k lens wear by culture of the lower
      conjunctiva. Further specimens were collected on six follow-up visits after
      beginning lens wear, as were samples from their lenses, cases, and suction
      holders. A questionnaire on lens care was administered after the fifth visit.
      RESULTS: Three subjects provided conjunctival samples yielding Staphylococcus
      aureus on one occasion before lens wear, one being positive for this organism
      after beginning lens wear. Of 38 subjects yielding no growth or only normal eye
      flora before use, 28 remained free of ocular pathogens after beginning lens wear.
      Only four subjects had positive cultures on more than one occasion after lens
      wear. There was no significant difference in isolation levels of pathogens with
      lens wear (p = 0.423). Lens culture of 54% of subjects yielded no growth or
      normal flora only; lenses of 16 subjects yielded potential pathogens, including
      three subjects contaminated on more than one occasion. Lens isolates did not
      match the organisms transiently colonizing the eye. Lens case, the most
      frequently contaminated item, was associated with lens contamination (p < 0.001),
      the same organism being isolated from both items in 11 subjects. Lens suction
      holder was less frequently contaminated. Neither lens case nor suction holder
      contamination was associated with isolates from the eye. Reported good compliance
      correlated with lack of contamination in all but one subject. The most frequent
      breaches in the lens care protocol were failure to clean, disinfect, and replace
      the lens case. CONCLUSION: Ocular flora was not altered by ortho-k lens wear over
      an extended period, and patients remained free of infection. Contaminants
      identified were generally of a transient nature. Most patients had significant
      contamination of at least one item, most frequently the lens case. Lens case
      isolates were significantly associated with those from the lens. The majority of
      patients reporting good compliance had low or no contamination of their lenses
      and accessories.

PMID- 15976582
TI  - The effects of high-Dk rigid contact lens center thickness, material
      permeability, and blinking on the oxygen uptake of the human cornea.
AB  - PURPOSE: The human corneal oxygen uptake responses associated with the static
      (nonblinking) and dynamic (blinking) wear of five rigid gas-permeable materials
      with high oxygen permeabilities were determined for three different center
      thicknesses and compared with the responses for the normal open eye and severe
      hypoxic stress (static wear of polymethylmethacrylate). METHODS: Corneal oxygen
      uptake rates were measured with a Clark-type polarographic electrode during two
      sessions with each of 10 human subjects. Measurements were made on the right eye
      for the normal open eye (air) and after 5 minutes of static and dynamic wear of
      polymethylmethacrylate and five rigid gas-permeable contact lens materials:
      Fluoroperm 92 (paflufocon A, Dk = 92), Fluoroperm 151 (paflufocon D, Dk = 151),
      1992 Menicon SF-P (melafocon A, Dk = 102), 1995 Menicon SF-P (melafocon A, Dk =
      159), and Menicon Z (tisilfocon A, Dk = 163-250). Lenses were manufactured in
      three different center thicknesses (0.12, 0.16, and 0.20 mm), with all other
      parameters remaining constant. Repeated-measures analysis of variance was used
      and included lens material (five levels), blinking condition (two levels), and
      lens thickness (three levels) as within-subject effects. RESULTS: Significant
      differences were found in corneal oxygen responses to lens material (p < 0.001)
      and lens thickness (p < 0.001), with lenses of lower oxygen permeability and
      thicker lenses being associated with higher oxygen uptake. No statistically
      significant differences were noted between static or dynamic wear of the lens
      materials (p = 0.59). CONCLUSIONS: For those very high Dk rigid lens materials
      studied here, moderate changes in lens thickness or material permeability may
      result in modest differences in corneal hypoxic relief, whereas blinking results
      in no significant improvement to corneal oxygenation.

PMID- 15976583
TI  - Beyond flux: total corneal oxygen consumption as an index of corneal oxygenation
      during contact lens wear.
AB  - PURPOSE: The purpose of this study is to compute total corneal oxygen consumption
      during contact lens wear and consider the concept as an index for describing
      corneal oxygenation during contact lens wear as opposed to flux, partial
      pressure, or Dk/t. METHOD: Estimates of total corneal oxygen consumption were
      generated using a previously described eight-layer model based on oxygen
      diffusion equations and using contemporary estimates of tear and corneal layer
      thicknesses. Relative consumption, expressed as %Q (percentage of normal
      consumption without contact lens wear), was also calculated for daily wear and
      continuous wear modes, thereby providing an index of the chronic hypoxic effect
      of contact lens wear. RESULTS: Corneal oxygen consumption is calculated to
      converge to the same value of 44.8 nL/cm/sec above a Dk/t of approximately 20 and
      300 x 10(-9) (cm/sec)(mL0(2)/mL/mm Hg) for the open and closed eye scenarios,
      respectively. Lenses with Dk/t values of 15 and 50 x 10(-9) (cm/sec)(mL0(2)/mL/mm
      Hg) allow about 96% of normal long-term total oxygen consumption without a
      contact lens in place for daily wear and continuous wear, respectively.
      CONCLUSION.: Total corneal oxygen consumption is based on physical parameters,
      represents a direct index of corneal oxygen metabolism and thus cellular energy
      (ATP) production, allows direct comparison between two lenses or a lens and
      nonlens-wearing state, and eliminates the ambiguity of other measures, thereby
      providing an attractive means of describing corneal oxygenation.

PMID- 15976584
TI  - Short-term adaptation of the human corneal endothelium to continuous wear of
      silicone hydrogel (lotrafilcon A) contact lenses after daily hydrogel lens wear.
AB  - PURPOSE: The purpose of this study is to assess whether improved oxygen
      availability to the cornea resulted in changes in the corneal endothelium.
      METHODS: Eighteen adult (average age 25.3 +/- 5.1 years) hydrogel lens wearers
      (average of 5.5 years prior daily lens wear, range 3-9 years) were refitted with
      silicone hydrogel lenses (Focus Night and Day) for continuous wear over 30 days
      and nights. They were assessed in detail immediately before the refit (baseline
      measures) and again after 6 months of wear with lens replacement every 30 days.
      Assessments included slit biomicroscopy (for grading of limbal and bulbar
      redness), corneal staining with fluorescein, and then by noncontact specular
      microscopy for central corneal thickness (CCT) and endothelial cell layer images.
      The endothelial images exported as JPEG files and printed at 7000x magnification.
      The cell-cell borders were marked and then the areas of an average of 255
      cells/image measured with a digitizer pad in stream mode. The number of cell
      sides was also counted. RESULTS: After 6 months of silicone hydrogel lens wear,
      most subjects showed an improvement in mean bulbar (1.1 to 0.9) and limbal
      redness (1.0 to 0.6, p < 0.001) and epithelial fluorescein staining (0.5 to 0.3)
      grades, and the mean CCT values decreased slightly in most subjects (0.527 to
      0.520 mm), although the decrease was not statistically significant (p = 0.565).
      The mean endothelial cell area also increased slightly (358 to 363 microm2; p
      nonsignificant [NS] = 0.701), whereas the mean coefficient of variation (COV)
      decreased slightly (30.2 to 29.1%, p NS = 0.357). The calculated mean endothelial
      cell density (ECD; area/1000000 microm2) also decreased slightly from 2821 to
      2774 cells/mm, but this change also was not statistically significant (p =
      0.620). However, the changes in ECD showed a very substantial relationship to the
      changes in CCT, i.e., as CCT decreased, so the apparent ECD decreased; this
      change was highly significant (r = 0.747, p < 0.001). This relationship was
      slightly stronger still when possible image magnification differences were
      corrected for. The percentage of six-sided ("hexagonal") cells increased slightly
      (58.3 to 60.1%). CONCLUSION: The results indicate that, in silicone hydrogel lens
      wearers exhibiting positive external eye signs thought to be associated with
      improved oxygen availability, subtle morphologic changes (marginally decreased
      polymegethism and pleomorphism) in the central region of the corneal endothelium
      can occur. It remains to be established, however, whether these changes can be
      directly attributed to oxygen effects (reduced hypoxia and hypercapnia altering
      the endothelial cells) or to a mechanical effect (in which changes in corneal
      thickness result in a reorganization of the corneal endothelium).

PMID- 15976585
TI  - Refractive and biometric changes with silicone hydrogel contact lenses.
AB  - PURPOSE: This study reports data from an 18-month longitudinal study of neophyte
      contact lens wearers and compares changes in ocular refraction and biometry
      induced by daily wear and continuous wear of two different silicone hydrogel
      (SiH) materials. METHODS: Forty-five subjects were enrolled in the study and
      randomly assigned to wear one of the two silicone hydrogel materials: Lotrafilcon
      A or Balafilcon A lenses on either a daily or continuous wear basis. Measurements
      of objective refraction, axial length, anterior chamber depth, corneal curvature,
      and the rate of peripheral corneal flattening were performed before and 1, 3, 6,
      12, and 18 months after initial fitting. RESULTS: Mean spherical equivalent
      refractive error increased in the myopic direction in all contact lens groups
      across time (p < 0.001). Axial length was the main biometric contributor to the
      development of myopia. After 18 months of lens wear, subjects in the Lotrafilcon
      A group showed the greater mean increase in myopia (i.e., -0.50 D). CONCLUSIONS:
      The results of this study show that increases in myopia, similar if not higher
      than those found to occur normally in young adult noncontact lens wearers, still
      occur with silicone hydrogel contact lens wear. The main biometric contributor to
      the progression of myopia was an increase in axial length. Differences between
      our results and those of previous studies with silicone hydrogel contact lenses
      could be attributed to the differing populations used in which both age and
      occupation may have played a role.

PMID- 15976586
TI  - The effect of overnight contact lens corneal reshaping on higher-order
      aberrations and best-corrected visual acuity.
AB  - PURPOSE: The purpose of this study is to determine the effect of higher-order
      aberrations after Corneal Refractive Therapy (CRT) on best-corrected visual
      acuity (BCVA) and the impact of pupil size on BCVA. METHODS: High-contrast (HC)
      and low-contrast (LC) Bailey-Lovie BCVA was measured in the morning before and
      after pupil dilation on 20 myopes (mean spherical equivalent -3.11 D +/- 0.96 D)
      under age 40. BCVA was measured again in the afternoon after dilation. Dilated am
      and pm aberrations were measured using the Complete Ophthalmic Analysis System
      (WaveFront Sciences). Patients were fit with CRT lenses in each eye. One month
      after finalizing the lens fit, BCVA and aberration testing were repeated. Average
      higher-order RMS error (third to sixth order), spherical aberration, third-,
      fourth-, fifth-, and sixth-order RMS error were calculated at each visit for a 3
      mm and 5-mm pupil. BCVA and aberration data were analyzed using a repeated
      measures analysis of variance. Linear regression was used to describe the
      relationship between aberrations and BCVA reductions after CRT. RESULTS: Mean
      refractive error changed by +3.33 D +/- 0.96 D. No clinically significant changes
      were found in HC BCVA post-CRT, whereas LC BCVA reductions of 0.07 logarithm of
      the minimum angle of resolution (logMAR) (nondilated, p = 0.002) and 0.12 logMAR
      (dilated, p < 0.001) were found. No additional decrease in HC BCVA was found
      after pupil dilation, whereas a mean additional decrease of 0.08 logMAR in LC
      BCVA was found with dilation post-CRT (p = 0.013). Higher-order RMS error
      increased for both 3-mm and 5-mm pupils (p < 0.0001) and remained stable between
      measurements. Spherical aberration increased for 5-mm pupils after CRT (p <
      0.0001). For a 5-mm pupil, a 0.1-mum increase in spherical aberration was
      associated with an additional decrease in LC BCVA after pupil dilation post-CRT
      of 0.056 logMAR (R = 0.382, p = 0.004). CONCLUSIONS: CRT results in reduced low
      contrast BCVA as a result of increased higher-order aberrations. Higher-order
      aberrations appear to be relatively stable after CRT. Spherical aberration
      appears to drive additional low-contrast BCVA losses as pupil size increases.

PMID- 15976587
TI  - Clinical performance of microchannel contact lenses.
AB  - PURPOSE: It has been suggested that microchannels placed on the posterior surface
      of hydrogel contact lenses increase transverse lens movement and therefore
      increase tear mixing. Lens designs, which can improve tear exchange without
      adversely affecting lens performance, may play a significant role in improving
      the safety of contact lens wear. Our aim was to investigate the effect of
      posterior lens surface microchannels on contact lens performance. METHODS: A
      randomized, single masked pilot study was conducted. Fifteen experienced hydrogel
      lens wearers were randomly assigned to wear a microchannel lens (MC) in one eye
      and a standard hydrogel lens design (STD) in the fellow eye over a period of 6
      hours. A range of objective and subjective clinical performance measures were
      assessed, including visual acuity, lens movement, comfort and patient preference.
      RESULTS: There were no significant differences between the MC and STD lenses with
      respect to vision measures, corneal staining, and bulbar and limbal redness (p >
      0.05). The MC lenses produced significantly less conjunctival staining than the
      STD lenses and showed greater lens movement in primary gaze (p < 0.05). Lens
      distortion with blinking was evaluated through topographic assessment of the
      contact lenses on eye, and no significant differences were observed in central
      distortion levels between the two lens designs (p > 0.05). Subjective evaluation
      of the lenses with respect to comfort, vision, and overall satisfaction did not
      vary significantly between the two lens types (p > 0.05). CONCLUSIONS: The
      results of this study suggest that posterior lens surface microchannels do not
      adversely affect contact lens performance or subjective lens preference over a
      short-term wearing period. The MC lenses appear to produce less physiological
      impact on the conjunctival surface than STD lenses with less conjunctival
      staining observed with the MC lenses. Clinical investigation of the performance
      of this type of lens design in a larger group of subjects, over longer wearing
      periods, is warranted.

PMID- 15976588
TI  - The effect of age on short-term orthokeratology.
AB  - PURPOSE: The purpose of this study is to investigate the effect of age on the
      response to short-term (one hour) open eye orthokeratology (OK) lens wear.
      METHODS: Sixty volunteer subjects were divided into three groups (n = 20 per
      group) comprising children (group I, mean age: 9.5 +/- 1.7 years), young adults
      (group II, mean age: 24.6 +/- 3.7 years), and older adults (group III, mean age:
      43.9 +/- 6.1 years). Subjects wore reverse-geometry lenses (BE; UltraVision Pty.
      Ltd., Brisbane, Australia) under open-eye conditions for 1 hour in one eye only.
      Unaided logarithm of the minimum angle of resolution (logMAR) visual acuity,
      corneal astigmatism calculated from simulated keratometric (SimK) readings,
      corneal asphericity and apical radius of curvature (Medmont corneal topographer),
      and total corneal, stromal, and epithelial thickness (Holden-Payor optical
      pachometer) were measured before and after lens wear. Two-tailed paired Student t
      test were used to examine changes after OK, and analysis of variance and
      Bonferroni post hoc t tests were used to compare between groups with a critical p
      value of 0.05. RESULTS: All groups showed statistically significant (p < 0.05)
      improvement in unaided visual acuity, a trend for more positive (less prolate)
      corneal asphericity, increase in apical corneal radius, and decrease in central
      total corneal thickness after OK lens wear. Compared with groups I and II, group
      III showed significantly less change (p < 0.05) in visual acuity, apical corneal
      radius, corneal asphericity, central total corneal thickness, and epithelial
      thickness. CONCLUSIONS: Corneal and visual changes found in this study confirm
      previous reports of the rapid effects of short-term OK lens wear. Older lens
      wearers showed a reduced or delayed response to reverse-geometry lens wear in the
      short term, suggesting a reduced corneal epithelial response to interventions
      with increasing age.

PMID- 15976589
TI  - Reduction of myopia from corneal refractive therapy.
AB  - PURPOSE: : The purpose of the study was to monitor the efficacy of corneal
      refractive therapy (CRT) lenses to reduce myopia over a 4-week period. Refractive
      error, keratometry, high and low contrast acuity, and subjective vision after 28
      days of using CRT contact lenses were measured. METHODS: : Twenty-three myopes
      wore CRT HDS lenses, Dk = 100. The Nikon autokefractor/keratometer was used to
      measure the refractive error and keratometric changes. Visual acuity was measured
      using computerized high and low contrast charts and the subjects completed visual
      analog scales characterizing their vision on a daily basis. Measurements were
      performed at baseline (before lens insertion before sleep), immediately after
      lens removal the next morning and at 1, 3, 7, and 14 hours after eye opening.
      Measurements were made on the days following 1, 4, 10, and 28 nights of lens
      wear. After 72 hours of no lens wear, these parameters were again measured to
      assess corneal recovery. RESULTS: : The pretreatment manifest refraction (mean of
      OD and OS +/- standard deviation [SD]) was -2.72 DS +/- 1.06 and -0.55 DC +/-
      0.40. Myopic spherical equivalent refractive error (+/- SD) decreased by 1.30 DS
      +/- 0.53 (range 0-3 D) immediately after lens removal on day 1 and by 2.59 DS +/-
      0.77 by day 28 (range 1.25-3.88 D). The cylinder remained unchanged. Uncorrected
      visual acuity improved by 5 lines after one night and reached 0.00 LogMAR (6/6)
      by day 4. Visual acuity was maintained throughout the day by day 10. The day and
      time effect of the spherical equivalent change and the central corneal radius of
      curvature were statistically significant (p < 0.01) up to day 10 and remained the
      same until day 28. Central (autokeratometer) Ks flattened by 1.28 D +/- 1.35
      after one night and 2.33 D +/- 1.30 by day 28. The subjective vision improved
      significantly from day 1 to day 28 (p < 0.01) and was maintained throughout the
      day from day 4 to day 28 (p < 0.01). All measures did not recover completely to
      baseline after 72 hours of no lens wear. CONCLUSIONS: : CRT lenses significantly
      reduced myopia, improved visual acuity and subjective vision, and flattened
      central corneal curvature. Maximal effect was achieved after 10 days and was
      maintained for the rest of the study period.

PMID- 15976590
TI  - The size, location, and clinical severity of corneal infiltrative events
      associated with contact lens wear.
AB  - PURPOSE: The purpose of this study is to determine the relationship between the
      size, location, and clinical severity of corneal infiltrative events (CIEs)
      associated with contact lens wear. METHODS: We examined a series of contact lens
      wearers, presenting consecutively to a large hospital clinic, who had any form of
      CIE. The severity of the CIE was quantified using a clinical severity matrix
      based on scores attributed to each of 10 signs and symptoms. The infiltrate was
      accurately drawn on a schematic diagram of the ocular surface, and from this, we
      determined its size (i.e., largest dimension) and distance from the limbus.
      Cartograms were constructed to illustrate the size and location of the corneal
      infiltrates according to wearing modality and lens type. RESULTS: Useable data
      pertaining to 111 patients were analyzed. A significant positive correlation was
      found between the distance of the infiltrate from the limbus versus clinical
      severity (p = 0.002), but not between the distance of the infiltrate from the
      limbus versus infiltrate size (p = 0.97). The cartograms revealed a tendency for
      infiltrates to occur in the superior cornea of patients wearing extended wear
      silicone hydrogel lenses (p = 0.0002) in the central cornea of patients wearing
      daily wear hydrogel daily disposable lenses (p = 0.007) and in the peripheral
      cornea of patients wearing daily wear hydrogel (excluding daily disposable)
      lenses (p = 0.0006). CONCLUSIONS: These data statistically validate the
      previously held anecdotal notion that CIEs which occur in the peripheral cornea
      are less clinically severe than those which occur in the central cornea.
      Consideration of the distribution of CIEs may facilitate a better understanding
      of the etiology of these events and can serve to alert practitioners as to their
      likely clinical presentation.

PMID- 15976591
TI  - Adverse events and discontinuations with rigid and soft hyper Dk contact lenses
      used for continuous wear.
AB  - PURPOSE: The purpose of this study was to assess the relative clinical success of
      hypertransmissible rigid and soft contact lenses in terms of the rates of adverse
      events and clinical discontinuations. METHODS: One hundred subjects (50
      experienced wearers and 50 neophytes) were fitted with either the Z-alpha lens
      (Menicon) or the Focus Night & Day lens (CIBA Vision), which were worn on a 30
      day continuous wear basis. The rates of adverse events and clinical
      discontinuations were monitored over 12 months. RESULTS: There were 20 adverse
      events that were categorized as being serious or significant--four with rigid
      lenses and 16 with soft lenses (p = 0.003). There was no significant difference
      between the experienced (10) and the neophyte (10) groups (p = 1.00). There were
      23 clinical discontinuations--13 with rigid lenses and 10 with soft lenses (p =
      0.46). Fewer experienced wearers (five) discontinued than neophytes (18) (p =
      0.002). CONCLUSIONS: Practitioners should anticipate fewer adverse events with
      rigid versus soft lenses prescribed for continuous wear. Experienced wearers are
      less likely to discontinue compared with neophytes.

PMID- 15976592
TI  - Comparative clinical performance of rigid versus soft hyper Dk contact lenses
      used for continuous wear.
AB  - PURPOSE: The purpose of this study is to investigate the comparative clinical
      performance of two hyper Dk contact lenses: a silicone hydrogel lens (Focus Night
      & Day, Ciba Vision) and a rigid lens (Z-alpha, Menicon Co. Ltd.) when worn for up
      to 30 days of continuous wear (CW). The rigid lens was worn on an unplanned
      replacement basis, whereas the soft lens was replaced monthly. METHODS: One
      hundred subjects were recruited. Fifty neophyte subjects were randomly assigned
      into one of the lens types (25 subjects per lens type). Twenty-five existing
      daily wear (DW) rigid lens users wore the rigid study lens and 25 existing DW
      soft lens users wore the soft study lens. Visual acuity, lens fit, keratometry,
      refraction, lens surface assessment, physiological response, and subjective
      response were investigated at baseline and after 1 week of DW and 24 hours, 1
      week, and 1, 3, 6, 9, and 12 months of CW. Analysis compared lens type (rigid vs.
      soft) and subject group (experienced vs. neophyte). RESULTS: Sixty-eight subjects
      completed the study. Visual acuity was similar for the two lens types and subject
      groups. Lens fit was judged to be adequate in all subjects. Corneal curvature of
      subjects in the rigid groups became flatter by 0.13 mm compared with 0.04 mm for
      subjects in the soft lens groups (F = 14.7, p = 0.0003); the refractive findings
      mirrored these corneal changes. The increasing rate of deposition on rigid lenses
      was consistent with the fact that these lenses were not replaced during the
      study. Conjunctival hyperemia and staining were similar for the two lens types
      but greater among experienced wearers at baseline (F = 13.8, p = 0.0005; F = 5.3,
      p = 0.02, respectively). Corneal staining was higher for the rigid lens wearers
      (F = 5.6, p = 0.02) but this was mainly the result of the initial higher scores
      in the rigid lens experienced group. The change in papillary conjunctivitis was
      greater for subjects in the soft lens groups than rigid lens groups (F = 4.6, p =
      0.04). Comfort was initially lower for the rigid lens neophyte group (F = 4.2, p
      = 0.0001), but after the CW phase started, there were no differences between
      groups. CONCLUSIONS: Notwithstanding subtle differences in physiological
      responses, continuous wear hyper Dk rigid and soft silicone-containing contact
      lenses can be successfully worn by both those with previous contact lens
      experience and those with no history of contact lens wear.

PMID- 15976593
TI  - Impact of previous extended and daily wear schedules on signs and symptoms with
      high Dk lotrafilcon A lenses.
AB  - PURPOSE: This study measured the impact of previous contact lens wearing schedule
      on the resolution of signs and contact lens-related symptoms among wearers of
      lotrafilcon A lenses. METHODS: One hundred forty adapted low Dk daily wear (DW)
      and 140 adapted low Dk extended wear (EW) subjects were enrolled and examined for
      1 year (overall study length is 3 years). All subjects wore lotrafilcon A lenses
      on a wearing schedule of up to 30 nights continuous wear with monthly replacement
      of lenses. Examinations were conducted at 1 week, 1, 6, and 12 months. RESULTS:
      The former EW wearers presented at baseline with significantly higher
      conjunctival staining and epithelial microcysts (p < 0.05) and lower ocular
      surface symptoms of end of day dryness than the former DW wearers. There were no
      significant differences in other ocular signs at baseline for the former DW and
      EW wearers. After use of lotrafilcon A, clinical signs of limbal, conjunctival
      redness, and neovascularization were significantly better by the 1-week visit for
      both groups of wearers. Regardless of former wearing schedule, symptoms of
      dryness (during and at the end of the day) and photophobia were significantly
      better after 1 week of lotrafilcon A use. The frequency and severity of symptoms
      of dryness during the day improved significantly among former low Dk DW and EW
      wearers within 1 week as did severity of dryness during the day for the former DW
      wearers, in part as a result of their higher prevalence at baseline in the DW
      group. Subjects reported redness improved significantly by the 1-month visit.
      CONCLUSIONS: Continuous wear of high Dk silicone hydrogel lenses resulted in an
      improvement in ocular redness and neovascularization and dryness symptoms among
      subjects in this trial, regardless of their previous low Dk lens-wearing
      schedule. All improvements in signs and symptoms were sustained through 12
      months.

PMID- 15976594
TI  - Survey of contact lens-wearing habits and attitudes toward methods of refractive
      correction: 2002 versus 2004.
AB  - PURPOSE: The purpose of this study is to measure patient attitudes toward methods
      of refractive correction among cross-sectional populations of contact lens
      wearers in 2002 and 2004 at the School of Optometry contact lens clinic at
      Indiana University. We also assessed the role of age and gender on these
      attitudes. METHODS: Attitudes toward methods of refractive correction were
      surveyed among 349 consecutive contact lens wearers in the spring of 2002 and
      compared with surveyed attitudes among 99 contact lens wearers in the winter of
      2004. The 23 questions in the survey queried attitudes on the health and safety,
      cost, and interest in methods of refractive correction in addition to questions
      about the wearing schedule for the subjects' current contact lenses (CL).
      Refractive methods that were compared included glasses, daily wear CL (DW), 7-day
      extended wear (EW) CL, 30-day continuous wear (CW) CL, LASIK, and orthokeratology
      (OK). The proportion of answers citing "agree" or "strongly agree" were combined
      and analyzed by chi-squared tests comparing the results for stratified groups in
      the previous and the current survey. The groups were stratified by gender and age
      over of under 30 years. Significance level was set at p < or = 0.05. RESULTS: In
      the 2004 survey, the age of the subjects was significantly younger. Subjects'
      interest in EW increased significantly in 2004 (59% vs. 45% with high level of
      interest 2004 vs. 2002, respectively; p = 0.015) and the proportion of subjects
      reporting overnight wear increased significantly (DW = 58% vs. 69% 2004 vs. 2002,
      p = 0.0017, controlling for age and gender). In 2004, glasses and EW CL were
      rated as more healthy compared with 2002 (glasses 95% vs. 88%, p = 0.05; EW CL
      48% vs. 34%, p = 0.005). Males are now less likely in 2004 to rate EW as healthy
      compared with females (38% vs. 53%, p = 0.01). In the 2004 survey, subjects over
      age 30 were significantly less interested in LASIK compared with those under age
      30 (59% vs. 33%, p = 0.02) and less interested than they were in 2002.
      CONCLUSIONS: In the 2004 survey, significantly more subjects reported overnight
      lens wear, an increased interest in, and opinion of overnight wear as a healthy
      method of refractive correction compared with the 2002 survey. There was some
      dampening of enthusiasm for LASIK among subjects over 30 years of age in the 2004
      survey. Age and gender can influence attitudes toward refractive correction, with
      females in this sample showing the most change over time, most probably as a
      result of different health information sources used by various demographic
      groups.

PMID- 15976595
TI  - Social marketing campaign significantly associated with increases in syphilis
      testing among gay and bisexual men in San Francisco.
AB  - BACKGROUND: Between 1999 and 2002, San Francisco experienced a sharp increase in
      early syphilis among gay and bisexual men. In response, the San Francisco
      Department of Public Health launched a social marketing campaign to increase
      testing for syphilis, and awareness and knowledge about syphilis among gay and
      bisexual men. METHODS: A convenience sample of 244 gay and bisexual men (18-60
      years of age) were surveyed to evaluate the effectiveness of the campaign.
      Respondents were interviewed to elicit unaided and aided awareness about the
      campaign, knowledge about syphilis, recent sexual behaviors, and syphilis testing
      behavior. RESULTS: After controlling for other potential confounders, unaided
      campaign awareness was a significant correlate of having a syphilis test in the
      last 6 months (odds ratio, 3.21; 95% confidence interval, 1.30-7.97) compared
      with no awareness of the campaign. A comparison of respondents aware of the
      campaign with those not aware also revealed significant increases in awareness
      and knowledge about syphilis. CONCLUSIONS: The Healthy Penis 2002 campaign
      achieved its primary objective of increasing syphilis testing, and awareness and
      knowledge about syphilis among gay and bisexual men in San Francisco.

PMID- 15976596
TI  - Comparison of acute and subclinical pelvic inflammatory disease.
AB  - OBJECTIVE: The objective of this study was to compare the demographic, clinical,
      and microbiologic findings in women with subclinical pelvic inflammatory disease
      (PID) and women with acute PID. STUDY: A cross-sectional study was performed
      using cohorts from 2 separate studies of 1293 women at risk for PID. Most
      participants were recruited from emergency departments, sexually transmitted
      disease clinics, and family planning clinics in metropolitan centers. We compared
      demographic, clinical, and microbiologic findings among women with acute PID,
      women with subclinical PID, and women without endometritis (controls).
      Statistical analyses included chi-square for categorical variables, calculation
      of odds ratio and 95% confidence intervals, and polychotomous logistic regression
      when appropriate. RESULTS: Similar proportions of women with acute and
      subclinical PID tested positive for cervical Chlamydia trachomatis (odds ratio
      [OR], 1.1; 95% confidence interval, 0.6-2.0) and had bacterial vaginosis (OR,
      0.7; 95% CI, 0.2-1.8). The rate of cervical Neisseria gonorrhoeae infection in
      women with subclinical PID was intermediate between the rates in women with acute
      PID and controls (21% vs. 49% vs. 7%, respectively, P <0.001, test for trend).
      Endometrial recovery of N. gonorrhoeae and C. trachomatis in women with
      subclinical PID was also seen at intermediate levels. Similar distributions of
      teenagers, women who smoked or used illicit drugs, and women engaging in sexual
      intercourse during menses were found in each group. Proportions of women with
      subclinical PID who were black and with lower education levels were intermediate
      between the proportions of these characteristics in women with acute PID and
      controls. CONCLUSION: Demographic and microbiologic characteristics of women with
      subclinical and acute PID are comparable. These findings suggest that the
      pathophysiological mechanisms of acute and subclinical PID are similar.

PMID- 15976597
TI  - A survey of sexually transmitted diseases/HIV coinfection testing and reporting
      practices among health care providers in New Jersey.
AB  - OBJECTIVES: A survey was conducted to ascertain the adherence of health care
      providers (HCPs) to national guidelines recommending human immunodeficiency virus
      (HIV) testing among persons with sexually transmitted diseases (STDs) and STD
      testing among HIV-infected persons. STUDY: A random sample of HCPs reporting STD
      and HIV cases in New Jersey were surveyed regarding their STD/HIV testing and
      reporting practices. RESULTS: Questionnaires were returned by 90 of 162 (55.5%)
      STD and 73 of 135 (54.1%) HIV HCPs. Sixty-six percent of STD HCPs reported
      offering HIV testing to persons with gonorrhea, chlamydia, or syphilis. However,
      up to 42.1% of HIV HCPs who managed HIV-positive patients never or almost never
      performed initial STD screening in these patients. Among HIV-infected patients,
      36.4% of HIV HCPs reported that they never or almost never conducted annual
      gonorrhea or chlamydia screening in women; 48.6% never conducted screening in
      men. CONCLUSIONS: Further efforts are needed to optimize the implementation of
      national guidelines for STD/HIV coinfection testing.

PMID- 15976598
TI  - Bacterial vaginosis (BV) and the risk of incident gonococcal or chlamydial
      genital infection in a predominantly black population.
AB  - OBJECTIVE: The objective of this study was to assess in prospective data whether
      bacterial vaginosis (BV) is associated with gonococcal/chlamydial cervicitis.
      STUDY: A total of 1179 women at high risk for sexually transmitted infections was
      followed for a median of 3 years. Every 6 to 12 months, vaginal swabs were
      obtained for Gram stain, culture of microflora, and Neisseria gonorrhoeae and
      Chlamydia trachomatis. A Gram stain score of 7 to 10 based on the Nugent criteria
      categorized BV. RESULTS: Baseline BV was associated with concurrent
      gonococcal/chlamydial infection (adjusted odds ratio, 2.83; 95% confidence
      interval [CI], 1.81-4.42). However, the association between BV and subsequent,
      incident gonococcal/chlamydial genital infection was not significant (adjusted
      relative risk [RR], 1.52; 95% CI, 0.74-3.13). Dense growth of pigmented,
      anaerobic Gram-negative rods (adjusted RR, 1.93; 95% CI, 0.97-3.83) appeared to
      elevate the risk for newly acquired gonococcal/chlamydial genital infection.
      CONCLUSIONS: BV was common among a predominantly black group of women with
      concurrent gonococcal/chlamydial infection but did not elevate the risk for
      incident infection.

PMID- 15976599
TI  - Risk of HIV transmission within marriage in rural China: implications for HIV
      prevention at the family level.
AB  - BACKGROUND: Little is known about HIV transmission at the family level in China.
      GOAL: : We examined the risks for HIV transmission between husbands and wives and
      from parents to children in a rural area where HIV spread among former commercial
      blood donors. STUDY: A cross-sectional study was conducted among 605 (302
      couples) marriage license applicants. RESULTS: More males (64.6%) than females
      (52.1%) reported having had premarital sex and multiple sex partners (12.6% and
      6.9%, respectively). Among those having had multiple sex partners, 8.5% reported
      often or always using condoms. Only 36.8% of the couples agreed that they would
      not plan to have a baby after knowing the status of HIV infection. Approximately
      43% of the couples agreed that they would use condoms consistently if 1 of them
      were HIV-positive. CONCLUSIONS: There is an urgent need for national programs to
      prevent HIV infection within couples in rural areas.

PMID- 15976600
TI  - The cost effectiveness of gonorrhea screening in urban emergency departments.
AB  - BACKGROUND: The prevalence of gonorrhea (GC) among adolescent and young women
      attending some urban emergency departments (EDs) ranges from 1% to 7%, but
      historically screening has not been logistically practical. GOAL: The primary
      goal of the study was to assess the cost effectiveness of GC screening in women
      ages 15 to 29, seeking care in urban EDs, using noninvasive or rapid point-of
      care tests. STUDY: We developed a state-transition Markov model to compare the
      net lifetime health consequences, costs, and cost effectiveness of routine ED
      care (no screening for women without genitourinary symptoms) to GC screening
      using 1 of 5 detection methods: Gram-stained smears of endocervical swab
      specimens, urine-based nucleic acid amplification tests (NAATs), NAATs performed
      on endocervical swabs, rapid immunochromotographic strip test (RIS) performed on
      clinician-collected vaginal swabs, and RIS on patient-collected vaginal swabs.
      RESULTS: Screening women between 15 and 29 years of age using urine-based NAATs
      prevented 1247 cases of pelvic inflammatory disease (PID) and saved 177 US
      dollars per patient compared with no screening. Compared with urine-based NAAT,
      screening with RIS using clinician-obtained vaginal swabs prevented an additional
      220 cases of PID and had an incremental cost effectiveness ratio of 6490 US
      dollars per quality-adjusted life year (QALY). Results were sensitive to
      assumptions about loss to follow-up, gonorrhea prevalence, and test costs.
      CONCLUSION: Screening females aged 15 to 29 for gonorrhea in some urban EDs will
      prevent substantial reproductive morbidity. Screening with rapid, point-of-care
      tests is cost effective compared with other well-accepted preventive
      interventions.

PMID- 15976601
TI  - Factors that influence the cost effectiveness of gonorrhea screening in emergency
      departments.

PMID- 15976602
TI  - A comparative study of condom use and self-reported sexually transmitted
      infections between foreign Asian and local clients of sex workers in Singapore.
AB  - OBJECTIVE: We conducted a survey to compare condom use and its associated factors
      between foreign Asian and local clients of female sex workers in Singapore.
      STUDY: A survey was conducted between 2001 and 2002 on a random sample of 810
      clients (677 foreign Asian workers and 133 locals) recruited from the streets and
      outside the brothels in Singapore. RESULTS: Foreign clients were more likely than
      locals to be inconsistent condom users with sex workers. Clients from China
      reported the highest percentage of inconsistent condom use (29.2%) and sexually
      transmitted infections (16.7%) compared with 8.3% (P < 0.003) and 2.3% (P <
      0.005), respectively, among locals. On multivariate analysis, inconsistent condom
      use among foreign clients increased significantly with the number of freelance
      sex workers. The reverse trend was found for local clients. CONCLUSION: There is
      a need to design separate condom-promotion programs for foreign Asian and local
      clients of sex workers in Singapore.

PMID- 15976603
TI  - Prevalence and correlates of chlamydia trachomatis, neisseria gonorrhoeae,
      trichomonas vaginalis infections, and bacterial vaginosis among a cohort of young
      injection drug users in Baltimore, Maryland.
AB  - OBJECTIVES: Injection drug users (IDUs) consistently demonstrate high-risk
      behaviors for sexually transmitted infections (STIs). This study examines STI
      prevalence and correlates among young IDUs. STUDY: This cross-sectional study
      recruited IDUs aged 18 to 30 years. Participants completed a behavioral risk
      assessment and were tested for chlamydia, gonorrhea, and trichomoniasis by
      nucleic acid amplification methods. Women were also tested for bacterial
      vaginosis (BV). Gender-specific analyses were done comparing infected with
      noninfected participants using chi-square, Mann-Whitney tests, and logistic
      regression. RESULTS: Of the 115 (35.3%) women and 211 (64.7%) men in the study,
      STI prevalence, respectively, was: chlamydia, 5.3% and 3.3%; gonorrhea, 3.5% and
      0%; and trichomoniasis, 8.6% and 1.9%. Most (68.0%) participants had 2 or more
      sex partners in the past 3 months, of whom fewer than half consistently used
      condoms. Independent correlates for prevalent STIs included douching (adjusted
      odds ratio [AOR], 4.9; 95% confidence interval [CI], 1.5-23.6) for women and anal
      sex with female partners (AOR, 6.3; 95% CI, 1.5-25.8) for men. BV prevalence was
      56.3% and was associated with douching (OR, 2.5; 95% CI, 1.1-5.7). CONCLUSIONS:
      Despite high sexual risk, STI prevalence among young IDUs was similar to that of
      the general population. BV prevalence was high, suggesting that future STI
      assessments among female IDUs should include BV.

PMID- 15976604
TI  - Polymerase chain reaction-based subtyping of ureaplasma parvum and ureaplasma
      urealyticum in first-pass urine samples from men with or without urethritis.
AB  - BACKGROUND: Our previous study suggested a significant association between
      Ureaplasma urealyticum and nongonococcal urethritis (NGU). However, association
      of the serovars of U. urealyticum with NGU remains unclear. A polymerase chain
      reaction (PCR)-based assay can distinguish 4 serovars of Ureaplasma parvum from
      each other and categorize 10 serovars of U. urealyticum into 3 subtypes: subtype
      1 (serovars 2, 5, 8, and 9), subtype 2 (serovars 4, 10, 12, and 13), and subtype
      3 (serovars 7 and 11). GOAL: The goal of this study was to determine which
      subtypes of U. urealyticum are associated with NGU as determined by PCR-based
      assay. STUDY: The prevalence of U. urealyticum subtypes in 106 ureaplasma
      positive men with urethritis was compared with that in 30 ureaplasma-positive men
      without urethritis. RESULTS: : In men with nonchlamydial NGU and men with
      Mycoplasma genitalium-negative nonchlamydial NGU, only U. urealyticum subtype 1
      (serovars 2, 5, 8, and 9) was detected significantly more often than in men
      without urethritis. CONCLUSION: This study suggests that subtype 1 of U.
      urealyticum (serovars 2, 5, 8, and 9) is associated with NGU independently of
      Chlamydia trachomatis or M. genitalium.

PMID- 15976605
TI  - Risk factors for early syphilis among gay and bisexual men seen in an STD clinic:
      San Francisco, 2002-2003.
AB  - BACKGROUND: Substantial increases in syphilis among gay and bisexual men have
      been reported in San Francisco. GOAL: To identify risk factors for early syphilis
      infection among gay and bisexual men attending the San Francisco municipal STD
      clinic (City Clinic). STUDY: Cross-sectional, self-administered, behavioral
      survey of gay and bisexual men attending City Clinic between November 2002 and
      March 2003 linked with electronic medical record data. RESULTS: Among 1318 gay
      and bisexual men surveyed, 53 (4.0%) were diagnosed with early syphilis. The
      final multivariate model included nonwhite race (OR = 2.1 [1.1-4.4]), HIV
      infection (OR = 3.9 [2.0-7.7]), using both methamphetamine and sildenafil
      (Viagra(R)) (OR = 6.2 [2.6-14.9]), using methamphetamine without sildenafil (OR =
      3.2 [1.3-7.6]), using sildenafil without methamphetamines (OR = 0.9 [0.3-2.9]),
      stronger gay community affiliation (OR = 2.3 [1.2-4.6]), and having recent
      Internet partners (OR = 2.1 [1.0-4.3]). CONCLUSIONS: Syphilis prevention efforts
      should address methamphetamine and sildenafil use among gay and bisexual men and
      require strong and substantive involvement with the gay community to address
      syphilis in San Francisco.

PMID- 15976606
TI  - Leg ulcers and the Urgocell Non-Adhesive wound dressing.
AB  - The objectives of this clinical trial were to evaluate the efficacy and tolerance
      of the Urgocell Non-Adhesive (NA) dressing in the local management of venous or
      mixed leg ulcers. The study was a non-comparative, prospective, multicentre (15
      centres) phase III, clinical trial. The studied population was composed of non
      immunodepressed adults presenting a venous or mixed leg ulcer, uninfected, non
      cancerous, present for less than 18 months. Patients were followed up for 6 weeks
      with a weekly visit, including a clinical examination, area tracings and
      photographs. Evaluation by nursing staff and patients was performed at each
      dressing changed. Forty-three patients were included, presenting a leg ulcer with
      a mean surface area of 10.7 cm2. The surface area was reduced by a mean of 38%
      after 6 weeks of treatment. Four local adverse events were deemed to be related
      to the tested treatment and acceptability was noted very good for patients and
      nursing staff. The Urgocell NA dressing, combined with compression therapy,
      promoted the healing of the chronic wounds under study. The good tolerance and
      acceptability of the tested dressing were greatly appreciated.

PMID- 15976607
TI  - Are we getting "value for money" in tissue viability?

PMID- 15976608
TI  - The wearing of compression hosiery for leg problems other than leg ulcers.
AB  - Many people have leg problems other than ulceration. Practitioners from one
      primary care trust in Suffolk considered nursing assessment of these patients and
      the fitting of prescribed compression hosiery where appropriate as a health
      promotion initiative. However, ongoing assessment adds to heavy clinical demands
      on community practitioners. Engaging with people to take greater responsibility
      for their health, and recognition that practice should be underpinned by credible
      evidence, provided the backdrop to a two-staged retrospective audit. Results are
      based on the nursing records of 101 patients wearing prescribed compression
      hosiery other than for previous venous ulceration. It was concluded that
      following an initial detailed holistic assessment, including ankle brachial
      pressure index, those patients who meet identified characteristics can be
      empowered to return for reassessment only if there is a change in their health
      status, or skin changes to their legs. An information leaflet is considered
      critical to this strategy.

PMID- 15976609
TI  - The Hampton-Gledhill 2-stage pressure risk-assessment system.
AB  - Pressure ulcers are largely preventable and, therefore, patients dying of large,
      necrotic pressure damage is an unacceptable situation. Lee Gledhill is both a
      nurse and a barrister and has been involved in many cases involving nurses facing
      court proceedings when their patients' primary cause of death is pressure ulcers.
      Sylvie Hampton, has acted as expert witness in some of these cases. It became
      obvious to the two authors that had healthcare assistants (HCAs) been more aware
      of how pressure damage could be detected and then prevented, some of the
      supervising nurses would not have been facing legal charges. The authors decided
      to produce a simple method of assessing first-stage skin changes for HCAs to not
      only recognize these changes, but also to have a framework in place describing
      the actions they need to take. This framework was produced as a card (the Hampton
      Gledhill 2-stage pressure risk-assessment system). The card is being validated in
      many nursing homes and hospitals around the UK and in Jersey.

PMID- 15976610
TI  - The management of malodour and exudate in fungating wounds.
AB  - The topic of malodour and exudate in fungating wounds is of particular interest
      and relevance for community nurses who care for patients with fungating wounds in
      the community setting. Community nurses can work together with community oncology
      and palliative care services to manage patients with fungating wounds at home,
      where once hospital admission would have been needed to provide the level of
      support and care these patients require. Fungating wounds present unique
      challenges and can be problematic as a result of the levels of exudate and
      malodour which they produce. This review sought to establish whether recent
      advances in wound care products and/or techniques, could be of value in the
      control of these symptoms. The review established that there is little clinical
      research into the care of fungating wounds, and that the development of new
      dressings and techniques for controlling malodour and exudate is badly needed.

PMID- 15976611
TI  - Nurses' work must be recognized and rewarded.

PMID- 15976612
TI  - Pressures on mental health units are affecting service.

PMID- 15976613
TI  - Acute hospital-based palliative care services for the older person.
AB  - With an increasing elderly population, estimated to rise to 26% of the UK's total
      population by 2020 (World Health Organization (WHO), 2004), this demographic
      represents a large area of potential referrals for hospital-based palliative care
      services. In planning service provision for this group, all nurses must examine
      current levels of access for older people to specialist palliative care services.
      This article explores barriers to the equity of access for older people to
      palliative care services, taking into account cultural, political, medical and
      ethical obstacles to the older person receiving evidence-based palliative care.
      The article analyses the benefits of palliative care involvement in a group who
      have multiple comorbidities and whose concerns, including adequate symptom
      control and assistance in making end-of-life decisions, reflect the philosophies
      inherent in the palliative care movement. Political- and clinical-based
      strategies in overcoming these barriers involving multidisciplinary working and
      education are necessary to ensure that the older person is being treated with
      dignity and fairness throughout his/her hospital journey.

PMID- 15976615
TI  - Managing exacerbations of chronic obstructive pulmonary disease.
AB  - The worldwide incidence of chronic obstructive pulmonary disease (COPD) is
      increasing and, in parallel, so is the social and economic burden. Mortality data
      underestimate COPD as a cause of death because the disease is more likely to be
      cited as a contributory rather than as an underlying cause of death, or may not
      be cited at all. By 2020, COPD is expected to be the third most common cause of
      death worldwide yet it receives less funding, publicity and fewer resources than
      is deemed necessary. The major burden of COPD falls on the patient and carer, and
      it is difficult to quantify. The quality of life of patients is evident and
      depends on the severity of their disease and their ability to adapt physically,
      socially and emotionally to the resulting disability. COPD leads to 30000 deaths
      per year in the UK. It is a considerable load to the NHS, particularly in the
      winter months when exacerbations occur most commonly; it results in 13% of all
      acute medical admissions.

PMID- 15976614
TI  - Caring for minority ethnic older people in nursing care homes.
AB  - This article aims to identify best practice guidance in relation to caring for
      minority ethnic older people in UK care homes that provide nursing care,
      highlighting key issues and identifying gaps that require redress. Current best
      practice guidance focuses on client issues, such as the recognition of cultural
      preferences, and organizational issues, such as workforce and the environment.
      However, while there is some best practice guidance regarding the care of
      minority ethnic older people in care homes, it is not sufficiently explicit. The
      article concludes by suggesting key strategies to help address the needs of
      minority ethnic older people in care homes.

PMID- 15976616
TI  - Documentation standards set by the Clinical Negligence Scheme for Trusts.
AB  - This article considers the role of the Clinical Negligence Scheme for Trusts in
      encouraging the establishment of good standards of documentation in those trusts
      which are members of its clinical risk pool. It considers its assessment scheme,
      its standards for record keeping and the role of the NHS Litigation Authority.

PMID- 15976617
TI  - A project to establish a skills competency matrix for EU nurses.
AB  - Enhanced nurse workforce mobility in the European Union (EU) is seen as a remedy
      to shortages of nurses in some EU countries and a surplus in others. However,
      knowledge of differences in competence, culture, skill levels and working
      practices of nursing staff throughout EU countries is not fully documented
      because currently no tangible method exists to enable comparison. The European
      Healthcare Training and Accreditation Network (EHTAN) project intends to address
      this problem by establishing an assessment and evaluation methodology through the
      compilation of a skills competency matrix. To this end, subsequent to a review of
      documentation and literature on nursing competence definition and assessment, two
      versions of a nursing competence self-assessment questionnaire tool have been
      developed. The final competence matrix will be translated and disseminated for
      transnational use and it is hoped that this will inform EU and national policies
      on the training requirements of nurses and nursing mobility and facilitate the
      promotion of EU-wide recognition of nursing qualifications.

PMID- 15976618
TI  - Staff nurse who disregarded authority, protocol and confidentiality.

PMID- 15976619
TI  - The relationship between nurses and doctors.

PMID- 15976620
TI  - [Treatment of tonsillitis].
AB  - Tonsillitis is a frequent infection. Most of cases are viral and require only
      symptomatic treatment. Tonsillitis due to Corynebacterium diphteriae, Neisseria
      gonorrhoeae and Fusospirochetosis require specific treatment. Antibiotic
      treatment of streptococcal tonsillitis is needed to avoid suppurative and non
      suppurative complications such as rhumatoid fever.

PMID- 15976621
TI  - [Primary ciliary dyskinesia. Clinical presentation and diagnosis].
AB  - Primary ciliary dyskinesia (PCD) is a genetic disease characterized by
      abnormalities in ciliary structure/function. OBJECTIVE: We analyzed the main
      clinical features and test results of PCD in order to evaluate their usefulness
      for diagnosis. PATIENTS AND METHODS: Retrospective study of 35 cases of PCD
      evaluated by the same team, with nasal brushings in all cases (special light
      microscopy) and electron microscopy and/or by isotopic mucociliary clearance
      study in some. RESULTS: In a cohort of 145 patients with suspected PCD, the
      diagnosis of PCD was established in 35 cases using a combination of compatible
      clinical features coupled with the study of nasal brushings: 13 females and 22
      males, average age at time of diagnosis 25 years, situs inversus in 12 patients
      (34%). CONCLUSION: In the absence of consensus in the literature for diagnosis of
      PCD, we propose the association of the following diagnostic criteria: upper
      airway and bronchopulmonary infections beginning often early in the life, more
      inconstantly situs inversus, familial cases of PCD, consanguinity, infertility
      and permanent and ubiquitous abnormalities of ciliary structure/function. Nasal
      brushing with ciliary study (special light microscopy) seems to be an easy and
      reliable diagnostic criterion. Electron microscopy is necessary for proving
      ultrastructural abnormalities.

PMID- 15976622
TI  - [The respiratory mucociliary system and its exploration in primary ciliary
      dyskinesia].
AB  - BACKGROUND: We analyzed the main characteristic features of the respiratory
      epithelium mucociliary system and the different tests of ciliary beat and
      mucociliary transport (mucociliary clearance). This knowledge is necessary for an
      often interdisciplinary diagnosis and treatment of primary ciliary dyskinesia.
      METHODS: Review of the literature and personal experience of the different tests
      of ciliary structure and function. RESULTS: This disease is characterized by
      abnormalities in ciliary structure/function. The genetic mechanisms and the
      ultrastructural abnormalities that are involved are heterogenous compared to the
      relative homogeneity of the clinical presentation. CONCLUSION: The diagnostic
      criteria are compatible clinical features (chronic upper airway and
      bronchopulmonary infections, situs inversus...) coupled with tests of ciliary
      structure and function.

PMID- 15976623
TI  - [Tympanic paragangliomas: analysis of a nine cases].
AB  - OBJECTIVE: The purpose of this work was to evaluate the diagnostic strategy and
      outcome of patients treated for tympanic paraganglioma. PATIENTS AND METHODS:
      Nine patients presented with tympanic paraganglioma were treated in our unit from
      1996 to 2003. There were eight women and one man, mean age 65 years. Surgery was
      performed in all nine patients. This retrospective analysis focused on revealing
      signs, diagnostic tools, surgical procedure for tumor resection, and short-, mid
      , and long-term functional outcome. RESULTS: The surgical procedure was well
      tolerated by all patients. There were no cases of postoperative mastoiditis. None
      of the patients experienced postoperative dizziness. Total tumor removal was
      achieved in seven patients. In one patient, incomplete tumor resection was
      decided in order to preserve facial motion. All patients but one were relieved
      from their tinnitus in the early postoperative period. In four patients,
      preoperative hearing levels were worsened by the surgical procedure, essentially
      through an alteration of preoperative conductive hearing loss. CONCLUSION: MRI is
      highly contributive to the diagnosis of tympanic paraganglioma, which should be
      evoked in patients with pulsatile tinnitus. Diagnosis should be established as
      early as possible to lower the postoperative morbidity. While surgery can provide
      cure and relieve tinnitus, there is a high risk of auditory deterioration.

PMID- 15976624
TI  - [Curthoys and Halmagyi Head Impulse test: an analytical device].
AB  - Described in 1988 by Curthoys and Halmagyi, the Head Impulse test enables
      checking the individual response of each of the six semicircular canals to fast
      head movements within less than one minute. Interpretation of test results
      requires careful clinical observation of the eye/head synchronism. But, due to
      the very short duration of the phenomenon, such synchronism is often difficult to
      confirm. This is so difficult that, sixteen years after its first description,
      the test is still rarely performed in daily practice. OBJECTIVES: We describe
      hereafter a device which allows confirmation of the positive or negative test
      results for each of the six canals without increasing test duration. METHOD: A
      high resolution and high light sensitivity video camera located in front of the
      patient's face at a distance of 80 cm is connected to a computer for automatic
      image analysis. RESULTS: With this device, the practitioner can confirm a
      positive test by simple observation on the videooculocephaloscope (HIT scope) and
      record an image for later reference. With videooculocephalography (HIT graph),
      movements can be recorded for analysis to quantify the deficit of each
      semicircular canal.

PMID- 15976625
TI  - [Chondrosarcoma of the cricoid].
AB  - OBJECTIVE: Chondrosarcoma of the larynx is a rare neoplasm generally observed on
      the cricoid. The purpose of this study was to define the most appropriate
      surgical management depending on tumor extension and histological grade. PATIENTS
      AND METHODS: Three males and one female were treated for chondrosarcoma of the
      cricoid between 1990 and 2003 in the Ear, Nose and Throat department in Tours,
      France. There were three grade I tumors and one grade II tumor. Tumor resection
      by thyrotomy was performed in two patients, total laryngectomy in one and laser
      desobstruction in one. RESULTS: The patient who underwent total laryngectomy
      remained in complete remission at five years. Among the two patients who had
      thyrotomy, one remained in remission at three years and the other experienced
      recurrence at four years and underwent a second operation. He died five years
      later due to another disease. Total follow-up was nine years. The patient treated
      by laser therapy achieved stabilization at twelve months. CONCLUSION: Computed
      tomography and histological grading enable choosing the best surgical procedure.
      Partial laryngeal surgery is indicated for small or low-grade chondrosarcomas.
      For large or high-grade tumors, total laryngectomy must be performed. In the
      event of patient refusal, laser desobstruction can provide clinical
      stabilization.

PMID- 15976626
TI  - [Lipoma of the skull base. A case report].
AB  - OBJECTIVES: Intra osseous lipomas are rare benign tumours that occur most
      frequently within the metaphysis of long bones. Involvement of the skull base is
      exceptional. We report a case of a lipoma of the skull base discovered
      incidentally. METHODS: A 45 year-old female patient consulted for galactorrhea
      with Hyperprolactinemia. RESULTS: MRI showed, in addition to the microadenoma, a
      high signal intensity T1 and T2 and fat saturated expansive lesion of the body
      and the right greater wing of the sphenoid. CT-scan of the skull base showed that
      this lesion was a well circumscribed fat containing and trabeculated lytic lesion
      leading to the diagnosis of a lipoma of the sphenoid. CONCLUSIONS: Lipomas of the
      skull base are exceptional. They are well recognized on CT-scan and MRI and in
      typical cases biopsies are not necessary. No treatment is necessary for
      asymptomatic lesions.

PMID- 15976627
TI  - [Nasal leishmaniasis: a case report].
AB  - OBJECTIVE: To report a nasal leishmaniasis diagnosed by septal perforation
      biopsy. MATERIAL AND METHODS: We report a case of septal perforation with crusty
      rhinosinusitis and nasal vestibulitis in a 54-year-old woman with cirrhosis.
      RESULTS: Mucocartilaginous biopsy revealed a mucosal leishmaniasis. Biological
      and radiologic findings were normal. Clinical follow-up with anti-parasitical
      treatment showed a regression of the patient's muco-cutaneous lesion and
      regression of her hepatic insufficiency. CONCLUSION: Biopsy of septal perforation
      is a useful diagnostic tool, advocated for differentiate infectious, neoplasic
      and inflammatory pathology. Leishmaniasis may be evoked in rhinologic pathology.

PMID- 15976628
TI  - [Lyon 2005: a new consensus conference on liver transplantation: why, when, and
      how?].

PMID- 15976629
TI  - [Sclerosing peritonitis].
AB  - Sclerosing peritonitis (also described as sclerosing obstructive peritonitis,
      encapsulating peritonitis, obliterative adhesive peritonitis, abdominal cocoon
      syndrome) is not well-known by the general surgeon; most reviews of this subject
      occur in the nephrology literature. Peritoneal dialysis and continuous
      hyperthermic peritoneal perfusion are the main causes. No controlled study exists
      to evaluate the optimal therapeutic approach. Pre-operative diagnosis is
      difficult since the clinical signs and radiologic findings are non-specific.
      Nevertheless, the diagnosis should be considered when small bowel obstruction
      with proximal dilatation, ascites, and thickened or calcified peritoneum are seen
      on imaging. The surgeon should recognize sclerosing peritonitis grossly when it
      is encountered and adapt his surgical strategy accordingly.

PMID- 15976630
TI  - [Lymph nodes and rectal cancer].
AB  - Nodal invasion is a major prognostic factor of rectal cancer. Lymphatic extension
      of rectal cancer usually involves the mesorectal nodes then the inferior
      mesenteric chain but in 14% of patients, particularly with cancer of the lower
      rectum, metastasic nodes can be observed in the internal or lumboaortic chains
      situated beyond the usual territory of nodal dissection. On average, 30 nodes are
      examined on a proctectomy specimen, but with wide interindividual variation. The
      tumor can be adequately staged if at least 15 nodes are examined with little risk
      of not recognizing nodal metastasis. Metastatic nodes of rectal cancer are almost
      always small, more than 90% measuring less than 10 mm and 70% less than 5 mm. The
      number of invaded nodes and the total number of examined nodes are prognostic
      factors for survival. Hypofrationated preoperative radiotherapy does not alter
      the nodal status but a long radiotherapy protocol (45 Gy over 5 weeks) reduces
      significantly the total number of nodes examined without changing the number of
      metastasic nodes. Micrometastases (measuring less than 2 mm), identified by
      immunohistochemistry or gene amplification, can be detected in 25 to 70% of nodes
      considered metastasis-free at the usual microscopic examination. The prognostic
      value of these micrometastases remains to be established. The first node draining
      the tumor (sentinel node), which can be detected rapidly with dye infusion,
      appears to provide a good picture of the nodal status, the risk of finding an
      invaded node if the sentinel node is metastasis-free is less than 5%.

PMID- 15976631
TI  - [Right hemicolectomy: the Achilles Heel in the evaluation of laparascopic surgery
      for colorectal cancers].

PMID- 15976632
TI  - [Laparoscopic treatment of ectopic pregnancy].

PMID- 15976633
TI  - [Strangulated femoral hernia].

PMID- 15976634
TI  - [Intra-corporeal anastomosis in laparoscopic right hemicolectomy].

PMID- 15976635
TI  - [Hematocolpos due to imperforate hymen].

PMID- 15976636
TI  - [HNPCC Syndrome].

PMID- 15976638
TI  - [A hydatid cyst of the liver destroying the biliary convergence: treatment by
      internal drainage].

PMID- 15976639
TI  - [Laparoscopic treatment of ventral hernias].

PMID- 15976640
TI  - [Does ligation of the splenic vein during caudal pancreatectomy necessitate
      splenectomy?].

PMID- 15976641
TI  - [The management of asthma: what conclusions at the end of the asthma campaign?
      Proceeding of a symposium December 6, 2004].

PMID- 15976642
TI  - [Colloquium: "Management of asthma: outcome after the asthma plan." Introduction
      and key points].

PMID- 15976643
TI  - [Asthma and the Public Health law. Elements of the introduction presentation].

PMID- 15976644
TI  - [The asthma schools].

PMID- 15976645
TI  - [The management of asthma in children].

PMID- 15976646
TI  - [Improving the management and the prevention of occupational asthma].

PMID- 15976647
TI  - [The interest of medical counsellors specialised in indoor environment in the
      management of respiratory diseases related to indoor air].

PMID- 15976648
TI  - [Education for improving treatment of asthmatics].

PMID- 15976649
TI  - [ASUR-ASUR2: an overview of the standardisation of treatment of acute asthma in
      intensive care].

PMID- 15976651
TI  - [The physician-patient relationship. A conflict of values].

PMID- 15976650
TI  - [Monitoring adult and adolescent asthmatics: the ANAES and AFSSAPS guidelines,
      September 2004].

PMID- 15976652
TI  - [Control of bronchial inflammation on asthma: why? and how?].

PMID- 15976653
TI  - [The implication of research organizations].

PMID- 15976654
TI  - [Meta-analysis of international quality of life studies].

PMID- 15976655
TI  - [The role of the patient in the management of asthma].

PMID- 15976656
TI  - [What is the role of the pneumologist in the management of asthma?].

PMID- 15976657
TI  - [What is the role of the physiotherapist in the management of asthma?].

PMID- 15976658
TI  - [Management of asthma: the role of the nursing staff].

PMID- 15976663
TI  - [Physeal distraction for limb length discrepancy and angular deformity].
AB  - PURPOSE OF THE STUDY: Physeal distraction or chondrodiastasis uses the growth
      plate as a zone of least resistance. Application of force thus provokes
      distraction and opening of the plate (Salter and Harris type I epiphyseal
      detachment). Progressive lengthening allows room for regenerate bone and enables
      limb lengthening and correction of angular deformations. MATERIAL AND METHODS:
      Twenty chondrodiastasis procedures were performed in fifteen patients. Mean age
      was 14.4 years (10.3-15.7). The underlying causes were trauma (n = 6),
      constitutional deformation (n = 8), infection (n = 2, distal lateral femoral
      epiphysiodesis), and malformation (n = 4). The localizations were: proximal tibia
      (n = 11), distal tibia (n = 4), distal femur (n = 4), distal radius (n = 1). The
      surgical procedure involved installation of an external fixator on either side of
      the physis after planification of the desired correction and taking into account
      the remaining growth potential of the physis. The distraction was performed by
      the patient at the rate of 1 mm per day. A one-sided external fixator was used
      for eleven patients (distal femoral correction and proximal tibial
      hemichondrodiastasis for angular deformation) and a circular fixator (to control
      3D correction) in nine. Complications were noted according to the four grades of
      severity described by Caton. RESULTS: Mean follow-up was 26.1 months. Epiphyseal
      detachment was achieved in all patients, even in the presence of an
      epiphysiodesis bridge, in 7.7 days on average (2-15 days). Mean lengthening was
      4.75 cm, mean angular correction was 22.2 degrees (mean preoperative angle 20.5
      degrees ). For chondrodiastasis (symmetrical physeal distraction), the mean
      duration of correction was 4.6 months (1-9), mean time to healing was 8.3 months
      (4-13) and mean healing index was 55.6 days/cm (Verone). For hemichondrodiastasis
      (asymmetrical physeal distraction), mean duration of correction was 1.3 months (1
      3), and mean time to healing was 2.7 months (2-5). The healing index was
      different and was 3 days per degree. Complications were studied using the Caton
      classification. There were 17 (85%) benign complications (not requiring revision
      under anesthesia) and 6 (30%) serious complications (requiring anesthesia and
      unplanned revision). There were 2 (10%) severe complications (knee flexion, ankle
      equinus). DISCUSSION: Chondrodiastasis has specific complications, mainly
      involving the distal femur (stiff knee, risk of septic arthritis). It provides
      rapid in situ correction resulting from epiphysiodesis bridges. The resection
      step proposed by Bollini is not necessary, but the growth plate is definitively
      sterilized. This implies that the procedure be used for preventive lengthening,
      depending on the predicted limb length discrepancy. This notion limits
      indications to older children. Besides the fact that several deformations can be
      corrected simultaneously, this technique does not require osteotomy and respects
      vascular supply to the regenerative tissue. It involves the physis responsible
      for the angular deformation or limb length discrepancy. It does not require
      internal fixation nor bone grafting and can be performed with weight bearing.
      Finally, the procedure can be adjusted as needed during the correction phase,
      with the patient in the standing position.

PMID- 15976665
TI  - [Patellar position and lateral approach for total knee arthroplasty in
      degenerative knees with lateral femoropatellar arthrosis].
AB  - PURPOSE OF THE STUDY: Patellar malposition is a well-recognized patellar
      complication after total knee arthroplasty. Such residual malposition is
      particularly frequent when the knee presents lateral femoropatellar arthrosis. We
      compared the radiological position of the patella after total knee arthroplasty
      in degenerative knees with lateral femoropatellar arthrosis performed via a
      medial or lateral approach with elevation of the anterior tibial tuberosity.
      MATERIAL AND METHODS: Twenty-six total knee arthroplasties were reviewed
      retrospectively. Thirteen prostheses had been inserted via a medial approach and
      thirteen via a lateral approach. A posterior stabilized implant was used with an
      original technique for insertion of the patellar implant. The only difference
      between the groups was the approach. In the "lateral" group, the lateral approach
      was used to raise the tibial tuberosity and perform lateral marginal
      patellectomy. The tibial tuberosity was reinserted in all cases without
      transposition. Preoperative and 3-month postoperative radiographs (weight
      bearing, AP, lateral, femoropatellar 30 degrees flexion) were reviewed.
      Preoperative patellar displacement was at least 5 mm. There was no difference
      between the two groups for age, gender, weight, height, joint motion, pre- and
      postoperative mechanical alignment (HKA), or preoperative patellar gliding (7.6
      mm in the "medial" group and 9.7 mm in the "lateral" group). RESULTS: Recurrent
      patellar dislocation occurred in one patient in the "medial" group and one
      patient in the "lateral" group had an anterior impaction of the tibial plateau
      following a fall. Patellar gliding was corrected in both groups: 0.7 +/- 1.8 mm
      in the "medial group" and 0.0 +/- 0 in the lateral group (p > 0.05). Residual
      patellar tilt was +4.2 +/- 3 degrees in the medial group (lateral tilt) and -3.3
      +/- 5.4 degrees in the lateral group (medial tilt) (p = 0.003). DISCUSSION:
      Pateller gliding was corrected irrespective of the approach. Conversely, the
      medial approach did not allow effective correction of patellar tilt. The lateral
      approach with elevation of the anterior tibial tuberosity did not increase
      morbidity compared with the medial approach. It enabled avoiding residual lateral
      patellar tilt which can be a source of patellar complications. We prefer this
      approach for arthroplasty on degenerated knees with lateral femoropatellar
      arthrosis.

PMID- 15976664
TI  - [Transverse radioulnar branch of the dorsal ulnar nerve: anatomic description and
      arthroscopic implications from 45 cadaveric dissections].
AB  - PURPOSE OF THE STUDY: We conducted an anatomic study of the transverse branch of
      the dorsal ulnar nerve to describe its morphology and position in relation to
      arthroscopic exploration portals. MATERIAL AND METHODS: Forty-five non-side
      matched anatomic specimens of unknown age and gender were preserved in formol.
      The dorsal branch of the ulnar nerve was identified and dissected proximally to
      distally in order to reveal the different terminal branches. The morphometric
      analysis included measurement of the length and diameter of the transverse branch
      and measurement of wrist width. We also measured the smallest distance between
      the transverse branch and the ulnar styloid process, and between the branch and
      usual arthroscopic portals (4-5, 6R, 6U) in the axis of the forearm. RESULTS: The
      transverse branch was inconstant. It was found in 12 of the 45 dissection
      specimens (27%). In two-thirds of the specimens, the branch ran over less than
      50% of the wrist width, tangentially to the radiocarpal joint. Mean nerve
      diameter was 1 mm. It was found 5-6 mm from the ulnar styloid process and was
      distal to it in 83% of the specimens. The dissections demonstrated two anatomic
      variants. Type A corresponded to a branch running distally to the ulnar styloid
      process, parallel to the joint line (10/12 specimens). Type B exhibited a
      trajectory proximal to the ulnar styloid process, crossing the ulnar head (2/12
      specimens). The relations with the arthroscopic portals (4-5, 6R, 6U) showed that
      the mean distance from the branch to the portal was 3.75 mm for the 4-5 portal
      (distally in 11/12 specimens), 3.68 mm for the 6R portal (distally in 10/12
      specimens), and 4.83 mm for the 6U portal (distally in 7 specimens and proximally
      in 5). DISCUSSION: To our knowledge, there has been only one report specifically
      devoted to this transverse branch. Two other reports simply mention its
      existence. According to the literature, the transverse branch of the dorsal ulnar
      nerve occurs in 60-80% of the cases. We found two anatomic variations different
      than those described in the literature. Based on our findings and data reported
      previously, we propose a new classification, describing two main types. In Type
      1, the transverse branch arises proximally to the ulnar styloid process;type 1A
      and type IB are described in relation to the direction of the branch. In Type II,
      the branch arises distally to the ulnar styloid process;type IIA and type IIB
      again being described in relation to the direction of the branch. On the
      tangential trajectory over the radiocarpal joint, the morphometric data show a
      zone of risk described by a rectangle measuring 10 mm wide (6 mm distal and 4 mm
      proximal to the ulnar styloid process) and covering 50% of the wrist width. The
      relations with arthroscopic portals describe a zone of risk corresponding to a 5
      7 mm radius circle centered on the portals (4-5, 6R, 6U), which includes 83% of
      the transverse branches.

PMID- 15976666
TI  - [Tibia nonunion after intramedullar nailing for fracture: decortication and
      osteosynthesis by medial plating].
AB  - PURPOSE OF THE STUDY: Intramedullar nailing is now widely used for fractures of
      the tibia. Extension of nailing indications to proximal, distal, and comminuted
      fractures has led to a significant rate of complications. The purpose of this
      study was to analyze decortication and medial plating for the treatment of tibial
      nonunion after intramedullary nailing. MATERIAL AND METHODS: Eighteen cases of
      aseptic tibial nonunion after nailing for fracture were treated in three women
      and fifteen men, mean age 39 years (19-57). The initial classification was open
      (n = 8), segmental (n = 3), single-focus (n = 15). The fracture site was inferior
      (n = 6), middle (n = 7), and superior (n = 2). Primary nailing used reaming in 15
      cases (83%), unreamed in 3 (17%) static in 13 and dynamic in 5. Four plaster
      cabts were also applied. Complications were: infection (n = 1), compartmental
      syndrome (n = 2), tibial nerve palsy (n = 1), dysesthesia (n = 2), and protrusion
      of the nail into the knee (n = 1). Dynamization was performed in 11 patients, one
      with additional bone graft and fibulectomy. Repeated reamed nailing was performed
      in one patient. Seven nonunions were atrophic and 11 were hypertrophic. There
      were 13 malpositionings associated with the nonunion. Treatment of the nonunion
      was performed 300 days on average (90-900) after nailing: cancellous bone graft
      was associated with decortication in four cases because of bone loss (n = 3) or
      atrophic nonunion (n = 1). RESULTS: Union rate was 94%. Mean time for union was
      108 days (80-180) with no significant difference (Student t-test) between
      atrophic (119 days) and hypertrophic (103 days) nonunion. Correction of the
      malposition was incomplete in seven patients, with angular malunion of less than
      6 degrees in five patients and greater than 10 degrees in two. One late infection
      occurred and finally healed after external fixation and antibiotic therapy. No
      skin necrosis occurred. Five patients had pain on the hardware. Removal was
      performed in one time and pain resolved. Improvement of knee and ankle stiffness
      was achieved in all patients. DISCUSSION: This technique has been used in our
      department since 1967. Different studies have found a union rate ranging from 94%
      to 100% with this procedure. Intramedullary nailing, sometimes associated with
      bone graft or decortication, is also used for tibial nonunion with a good rate of
      union. The main problem of intramedulary nailing for nonunion, as for fracture,
      is the difficulty in avoiding malunion. Plating a nonunion, as a fracture,
      enables better reduction. Skin problems can occur with the medial plate if the
      soft tissues are damaged. This situation is very uncommon in secondary surgery.
      CONCLUSION: Decortication and medial plating was a safe and efficient treatment
      for tibia nonunion after failure of intramedullary nailing and allows better
      reduction and repeated nailing.

PMID- 15976667
TI  - [The accessory soleus muscle: a report of 21 cases and a review of the
      literature].
AB  - PURPOSE OF THE STUDY: Well known to anatomy specialists, the accessory soleus
      muscle was first demonstrated to be involved in painful syndromes in 1965 (Dunn).
      This supranumerary muscle situated in front of the calcaneum can be taken for a
      soft tissue tumor. The purpose of this work was to report a series of 21 patients
      with an accessory soleus muscle and to present the characteristic features,
      diagnostic methods, and treatment indications and modalities. MATERIAL AND
      METHODS: This series included 20 patients (one symptomatic bilateral case),
      fourteen men and six women, mean age 25 years. Seventeen patients practiced
      sports and ten had had a prior operation. All patients complained of exercise
      related pain. The physical examination was normal with the exception of a
      tumefaction, which was soft at rest and hard at triceps contraction against
      resistance, lying laterally to the Achilles tendon. We studied plain x-rays,
      ultrasound studies, computed tomographies, and electromyograms and later MRI
      which became the reference method to demonstrate the details of normal muscle
      structure. Ten patients (one bilateral case) were not particularly bothered by
      the supernumerary muscle. Functional treatment was given and provided patient
      satisfaction. For the other ten patients, who wished to continue their physical
      activities, two underwent fasciotomy (including our first case where fasciotomy
      was undertaken because a tumor was suspected) and eight underwent resection of
      the supranumerary muscle. RESULTS: The patients were followed for 6 to 19 years.
      Outcome was very good in all patients who were free of pain and had complete
      joint movement with symmetrical muscle force. Normal sports activities were
      resumed. DISCUSSION: The accessory soleus muscle is found in 10% of individuals.
      It is often asymptomatic. The muscle inserts on the anterior aspect of the soleus
      muscle or on the posterior aspect of the tibia or the muscles of the deep
      posterior compartment. It lies anterior to the calcaneal tendon and terminates on
      the calcaneal tendon or the superior or medial aspect of the calcaneus via fleshy
      fibers or a distinct tendon. Frequent in primates, this anatomic variant is
      present during embryological development. Its persistence depends on phylogenetic
      evolution. Among other hypotheses (exercise-induced intermittent claudication,
      compression of the tibial nerve, excessive tension on the nerve innervating the
      accessory soleus muscle), this supranumerary muscle is generally considered to be
      the cause of a localized compartment syndrome. Pain experienced during exercise
      is the only symptom regularly reported by patients. A careful examination is
      required to rule out another local cause. Besides tumefaction lateral to the
      Achilles tendon, often found bilaterally, there is no other clinical sign. Plain
      x-rays, ultrasound and computed tomography simply demonstrate a "mass" in front
      of the Achilles tendon. MRI is the examination of choice enabling confirmation of
      the muscle nature of the mass and ruling out the possible diagnosis of tumor.
      Since there is no risk of aggravation, surgical treatment can be avoided if there
      is no complaint. If the patient is seriously impaired, surgery can be proposed.
      In our opinion, complete resection of the supernumerary muscle is the safest
      solution and should be preferred over simple fasciotomy.

PMID- 15976668
TI  - [Posterior ankle impingement syndrome: a retrospective study in 21 cases treated
      surgically].
AB  - PURPOSE OF THE STUDY: The purpose of this work was to describe the posterior
      ankle impingement syndrome and to present a retrospective analysis of results
      after surgical treatment in 21 patients with a mean five years follow-up.
      MATERIAL AND METHODS: Twenty-one patients with a posterior ankle impingement
      syndrome underwent surgery between 1991 and 1999. There were 17 men and four
      women, mean age 33 years (18-45); 71% practiced sports, half at the competition
      level. For 71% of the patients, there was an acute fracture with nonunion of the
      posterior process of the talus; a microtrauma context was identified in 29%. The
      physical examination revealed pain at passive forced plantar flexion in 94% of
      patients with limping during exercise in 88%. Plain x-rays showed a long tail on
      the talus in 87% of the patients, a short tail in 9%, and a trigone bone in 4%.
      The posterior malleolus (or third tibial malleolus) was remodeled in 9%. Other
      examinations performed preoperatively completed the topographic analysis: 99Tc
      bone scintigraphy, computed tomography with 2D reconstruction and horizontal
      slices, MRI. The patients were placed in the ventral prone position for surgery
      via a para-achilles approach, medial in ten patients and lateral in eleven. Bone
      resection with combined arthrolysis of the subtalar and tibiotalar joints was
      performed in 20 patients (17 with nonunion of the posterior talar process, one
      with a trigone bone, two with malformed callus of the posterior malleolus). A
      soft tissue procedure was also performed in three patients (resection of a
      synovial cyst in one, tenosynovectomy of the long flexor of the great toe in
      two). RESULTS: All patients were reviewed clinically and radiographically (plain
      x-rays). The AOFAS score was determined. There were no cases of infection. Mean
      follow-up was five years (range 3-10). Results were excellent with a mean Kitaoka
      score of 90/100, varying with cause and type of procedure performed. Only one
      patient was dissatisfied (Kitaoka score 67/100); this patient presented residual
      dysesthesia in the territory of the posterior tibial nerve. In 90% of the
      patients, there was no sign of degeneration of the peritalar joints (two patients
      exhibited minimal remodeling of the posterior subtalar joint). 90% of the
      patients were satisfied or very satisfied. DISCUSSION: The posterior ankle
      impingement syndrome includes several pathological entities with similar clinical
      expression. It involves both bony and soft tissue elements in the posterior
      peritalar region. Repeated or acute forced plantar flexion is the main cause.
      Complementary explorations (bone scintigraphy, CT, MRI) besides standard
      radiography, are indispensable to obtain a definitive diagnosis and demonstrate
      the functional and mechanical impairment. Surgical treatment is simple via a
      posterior approach (posterolateral or posteromedial)) and in our hands has
      provided very good results without arthritic consequences at mid-term.

PMID- 15976669
TI  - [Sequelae of intra-articular calcaneal fractures: patterns and management].
AB  - PURPOSE OF THE STUDY: We reviewed retrospectively 24 feet with sequelae of
      transtalar process fractures of the calcaneum in order to identify the lesion
      pattern and determine optimal management options, both for acute and sequelar
      lesions. MATERIAL AND METHODS: There were fourteen men and nine women, mean age
      42 years (19-73). Twenty-three had subtalar osteoarthritis, eight had
      calcaneocuboid osteoarthritis, and fifteen had lateral submalleolar conflicts.
      There were twelve fibular tendon dislocations or fissurations, three tarsal
      tunnel syndromes, and two plantar splinters. Prior to treatment, all patients
      complained of pain. Preoperatively, walking distance was less than 500 m for
      thirteen patients, 2000-3000 m for four, and greater than 3000 m for five. Mean
      subtalar joint motion was 30% (0-100%) compared with the healthy side and mean
      frontal misalignment of the rear foot was 6 degrees valgus. Physical examination,
      podoscopy and x-rays were obtained in all patients. The Kitaoka score was noted.
      RESULT: Mean follow-up was 36 months (24-72). Sequelae were treated with a single
      procedure or with combinations: subtalar arthrodesis (n = 23) including one in
      association with calcaneocuboid arthrodesis, tension on fibular tendons (n = 7),
      neurolysis of the posterior tibial nerve (n = 3), resection of plantar splinters
      (n = 2), resection of the lateral shell (n = 14), and osteotomy (n = 2) to lower
      the greater tubercle of the calcaneum because of pain when wearing shoes. The
      mean Kitaoka function score was 31.7/100 (14-79) preoperatively. After treatment,
      the mean score was 81.7/100 (31-94), giving a 73.2% gain. The outcome was
      considered good in sixteen feet, fair in six, and poor in two. Mean walking
      distance was greater than 3000 m for 18 patients. Mean frontal misalignment of
      the rear foot under loading was 4.5 degrees valgus and the podoscopy demonstrated
      flat foot in thirteen patients. Three subtalar arthrodesis required revision for
      nonhealing. DISCUSSION: Initial treatment of a fracture, particularly an
      articular fracture, of the calcaneum must avoid disabling postoperative pain and
      shoe wearing problems. These sequelae basically concern: subtalar and
      calcaneocuboid arthritis, lateral submalleolar conflict, fibular tendon injury,
      plantar splinters, tarsal tunnel syndrome, loss of height, and misalignment of
      the rear foot. At the sequelar stage, the physical examination is primordial to
      confirm the lesion and search for any complication which could develop later
      postoperatively when walking distance becomes longer. For nine patients with
      residual pain, four resulted from lesions which were missed at the preoperative
      physical examination. Arthrodesis of the subtalar joint should be preferred over
      realignment of the rear foot and can be associated with the treatment of
      conflicts. This management scheme allows treating during a single operative time
      all sequelae, thus limiting recovery time. A scan of the ankle and foot with or
      without opacification of the fibular tendons is needed to confirm the physical
      examination which, for us, remains the key to successful surgery.

PMID- 15976670
TI  - [Scarf osteotomy for the treatment of hallux valgus: a review of 123 cases with
      4.8 years follow-up].
AB  - PURPOSE OF THE STUDY: Many different osteotomies can be used for the treatment of
      hallux valgus. The purpose of this study was to evaluate the Scarf osteotomy
      associated or not with phalangeal osteotomy and to search for deformation cutoff
      points beyond which corrections appear to be difficult to achieve. MATERIAL AND
      METHODS: This retrospective analysis included 87 patients (123 feet) among 130
      who underwent hallux valgus surgery between October 1993 and November 2000. Mean
      follow-up was four years eight months. The serie included 83 women and 4 men.
      Mean age at surgery was 53.5 years. A Scarf diaphyseal osteotomy was performed in
      all patients associated or not with phalangeal osteotomy. Each patient was
      reviewed clinically and radiographically with anteroposterior and lateral views
      of the foot in the standing position. RESULTS: 84.6% of the patients were
      satisfied or very satisfied. There was a correlation between the index of
      satisfaction and clinical symptoms (metatarsalgia, stiff hallux, pain over
      exostosis). There was a statistically significant decrease in hallux valgus (31.2
      degrees to 17.5 degrees ), of metatarsus varus (12.1 degrees to 7.5 degrees ),
      and articular angle of the distal metatarsus (13.3 degrees to 11.1 degrees ).
      Patients who had phalangeal osteotomy achieved the best hallux valgus correction
      (15 degrees versus 21.4 degrees ). Mean shortening of the first metatarsus was
      2.2 mm with a decrease in the metatarsus-ground angle (19 degrees versus 20.1
      degrees ). Cutoff limits for deformations which are difficult to correct
      satisfactorily were M1M2 angle > or = 15 degrees and distal metatarsal articular
      angle > or = 13 degrees . The overall Groulier score showed 70.7% very good and
      good results, 27.6% fair results and 1.7% poor results. DISCUSSION: The Scarf
      technique is a reliable method to achieve significant correction of hallux valgus
      deformation. It requires a rigorous technique with specific attention to the
      elevation of the first metatarsus and excessive shortening, two factors favoring
      metatarsalgia. Adding a phalangeal osteotomy can improve the radiological result,
      but it is very difficult to obtain satisfactory correction if the initial
      deformations are severe and associated. Rotation of the plantar fragment helps
      for better orientation of the articular surface of the first metatarsus but
      limits the correction of the metatarsus varus. Function is the basic objective of
      hallux valgus surgery and patient satisfaction is related solely to clinical
      symptoms.

PMID- 15976671
TI  - [Hydatid cysts in muscles: eleven cases].
AB  - PURPOSE OF THE STUDY: Echinococciasis or hydatid disease is a cosmopolite
      antropozoonosis common to humans and several mammal species. The disease results
      from the development of the larval or hydatid form of the canine tenia
      (Echinococcus granulosis) in the organism. Hydatic cysts are uncommonly found in
      muscles, even in endemic zones. The purpose of this work was to describe the
      epidemiological, clinical and therapeutic aspects of hydatid cysts observed in
      muscles based on our clinical experience and data in the literature. MATERIAL AND
      METHODS: For this study, we collected data on eleven cases of hydatid cysts in
      muscles treated surgically at the Sousse University Hospital in Tunisia over a 17
      year period from 1985 to 2002. We noted epidemiological, clinical,
      ultrasonographic and laboratory data which were analyzed to better detail the
      characteristic features of these localizations. RESULTS: Mean patient age was 30
      years (range 7-50). All patients lived in rural areas where sheep raising and
      contact with dogs was common. Patients consulted for a tumefaction of the soft
      tissue which increased in volume progressively. The muscle focus was generally
      unique and primary. The proximal muscles of the limbs were involved
      predominantly. Ultrasonography was performed for nine patients and suggested the
      diagnosis in all cases. The typical feature was a liquid echostructure in an
      endemic context. Computed tomography was performed in four patients with deep
      cysts. Magnetic resonance imaging was not used. Surgical treatment was used in
      all cases with a pericystectomy in six. Early outcome was favorable excepting one
      case of suppuration of the resection zone observed in one woman. At 2.5 years,
      there have been no cases of local or distant recurrence. DISCUSSION: Several
      factors would explain the exceptional nature of muscle localizations of hydatid
      cysts: efficacy of the hepatic and pulmonary barriers, muscle environment not
      favorable for growth of hydatid larvae. The predominant localization in the
      proximal muscles of the lower limbs could be explained by the volume of the
      muscle mass and its rich blood supply. It is important to establish the diagnosis
      preoperatively in order limit the risk of anaphylactic shock or dissemination in
      the event of puncture or accidental opening of the cyst during resection.
      Ultrasonography is the diagnostic tool of choice. Surgery is required for
      treatment, ideally by en bloc total pericystectomy. Medical treatment with
      imidazoles has little efficacy for the treatment of muscular hydatid disease.
      CONCLUSION: Hydatid cysts are rarely found in muscles, even in highly endemic
      zones. The diagnosis must nevertheless be entertained depending on the clinical
      and endemic context. Ultrasonography, and accessorily magnetic resonance imaging,
      are the exploration tools of choice to confirm the diagnosis before surgery and
      avoid puncture. Exclusively surgical treatment is indicated, ideally for total
      pericystic resection without rupture.

PMID- 15976672
TI  - [Glomus tumor in the quadriceps ligament: a case report].
AB  - We report a very rare localization of glomus tumor: the quadriceps ligament. The
      clinical diagnosis in this 19-year-old male patient was difficult. The final
      diagnosis was established at pathology examination of the surgical resection
      specimen. Resection provided cure. A review of the literature confirms that the
      quadriceps is a very rare localization of glomus tumor, no other cases have been
      reported previously.

PMID- 15976673
TI  - [Traumatic fibular tendon dislocation combined with medial malleolar fracture: a
      very uncommon association in ankle trauma].
AB  - We report two unusual cases of ankle injury involving dislocation of the fibular
      tendon and fracture of the medial malleolus. Only one case has been reported
      previously in the literature. We discuss the pathogenic mechanisms and the
      clinical and radiological aspects of this unusual ankle injury. The importance of
      early surgical treatment is emphasized.

PMID- 15976674
TI  - [The drug industry: a national issue].
AB  - Following up on a letter received from the Mrs. Nicole Fontaine, the Delegate
      Minister of Industry, requesting recommendations concerning the "serious threats"
      to the French drug industry, the Academy of Medicine auditioned the five leading
      French pharmaceutical firms and two foreign firms. Their complains led to
      proposals for six recommendations: recognize the strategic importance of the drug
      industry, conclude several years of contracts between the Economic committee on
      health products and the drug industry, facilitate clinical trails of drugs in
      France, favor relations between the national drug industry and university
      research centers, Inserm, Cnrs and the administration, encourage the development
      of biotechnology firms which represent one of the most promising areas of
      therapeutic research, propose the creation of an interministerial drug counsel
      presided by the Prime Minister to establish and implement a common national
      strategy.

PMID- 15976675
TI  - [Pharmacology, an innovative factor in therapeutic research].
AB  - As members of the pharmacology training group set up by the committee of
      pharmacological science of the French Academy of Pharmacy, we examine the
      situation of pharmacology in drug discovery. Today, it is obvious that by
      integrating genome sequencing, cellular and molecular biology, and
      bioinformatics, pharmacology has become a cross-disciplinary science.
      Pharmacologists must become knowledgeable in a wide range of domains, using the
      major points in each to direct them towards the discovery and development of new
      therapeutic agents. It is also clear that pharmacology remains a major factor in
      the different steps of drug discovery, from the molecular and cellular stages, to
      clinical and pharmaceutical developments.

PMID- 15976677
TI  - [Conclusion.]

PMID- 15976676
TI  - [New tools for preclinical pharmaceutic research].
AB  - Despite constantly growing expenditures for pharmaceutical research, which have
      double in the last ten years, the number of new drugs marketed in the world has
      continued to decline. The last decade has nevertheless seen a series of major
      methodological advances in the fields including pharmacogenomics,
      pharamcogenetics, high-flow screening, and structural biology, all considered to
      contribute to the discovery of "drugs of the future". Systemic screening of
      compound banks has become the starting point for nearly all drug research. It is
      nevertheless only the first step towards a drug (typically lasting a few months
      compared with ten years before the final drug is marketed). For a compound to
      passe from a leading screening compound to a marketed drug, its often
      contradictory properties (solubility, permeability, duration of action, activity,
      selectivity, absence of toxicity) must undergo a long multidimensional
      optimization process. The development of easily interpreted low-cost in vitro
      tests allow prediction of these properties without animal experimentation,
      greatly facilitating the multidisciplinary process.

PMID- 15976678
TI  - [Optimization of good use of medicinal products].
AB  - Optimization of good use of medicinal products is aimed at allowing the patient
      to benefit fully from the efficacy of the prescribed treatment while limiting the
      negative impact of adverse effects. The prescriber and the dispensing pharmacist
      have an important complementary role crucial for the good use of medicinal
      products. This potential must be developed and improved. Patients' awareness
      should be reinforced, particularly be encouraging their dialogue with healthcare
      professionals. Improvement of the current situation can be based on self
      appropriation of suitable information by each of the participants, leading to
      changing behavior. Common elaboration and diffusion of recommendations by the
      French National Academies of Medicine and Pharmacology would allow significant
      progress in good use of medicines.

PMID- 15976679
TI  - [Prescriptions in cardiology].
AB  - Prescriptions in cardiology have progressed from the often empirical and
      approximate approach used in the past to more rational approach based on the
      results of large clinical trials. For high blood pressure, bi- or even tri
      therapy is often necessary. For coronary heart disease, betablockers, aspirin,
      calcium inhibitors, statins and converting enzyme inhibitors constitute the
      mainstay drugs. For myocardial infarction, the crucial point is to restore
      muyocardial perfusion as quickly as possible by thrombolysis or angioplasty.
      Polytherapy is required for heart failure. Finally, for atrial fibrillation,
      after anticoagulation, sinus rhythm can be restored with anticoagulant cover can
      be obtained with electrical shock or antiarrhythmic drugs.

PMID- 15976680
TI  - [Adverse drug effects: a prospective study by Apnet performed in seven emergency
      care units in France: propositions for preventive measures].
AB  - Various studies have shown that adverse drug effects (ADEs) are a substantial
      cause of hospital admissions. However, little is known about the incidence and
      severity of ADEs resulting in hospital visits. To address this issue, we
      conducted a prospective survey in primary care and emergency departments of
      French public hospitals. This study was performed over two periods of one week,
      one in January, February and one in June 2003, in primary care and emergengy
      departments of four university hospitals and three general hospitals throughout
      France. Out of a total of 1826 patients consulting, 1663 were taking at least one
      drug during the previous week and were included for analysis according to the
      protocol. Altogether, 370 (22.2%; IC 95: 20.2-24.3%) of these patients receiving
      at least one drug consulted because of an ADE. From these 370 patients, 263
      (15.8%) where considered as touched by a probably (12), likely (13) or very
      likely (14) ADE. The sex ratio was the same in both groups with or without ADE
      (0.88%; P=0.95). Patients with ADE were older than those without (62.4 vs 53.8
      years, P=0.0016). Furthermore, ADE patients were more likely to have a higher
      severity score than no-ADE group (P=0.0003). The outcome seemed to be worse in
      patients with an ADE. The percentage of patients treated with 2 or more drugs and
      the number of drug exposures were significantly higher in patients with ADE than
      in those without (93.2% vs 84.2%, P<0.0001, and 5.8 vs 4.5 P<0.0001,
      respectively). The most frequent causes of visits for ADE-patients were digestive
      (n=38: 14.4%), neurological (n=23: 10.6%), malaise (n=48: 18,2%) events. The most
      frequently incriminated drug classes were (1) psychotropic agents, (including
      anxiolytics, hypnotics, antidepressants and antipsychotics), (2) diuretics (3)
      anticoagulants, (4) other cardiovascular drugs and (5) analgesics, including non
      steroidal anti-inflammatory agents. In 150 cases (40.8%; IC 95: 33.7% - 45%), the
      ADE was considered to be preventable because a contra-indication or a warning
      about drug use had not been respected.

PMID- 15976681
TI  - [Conclusion.]

PMID- 15976682
TI  - [The renin-angiotensin system: current data].
AB  - The renin-angiotensin system (RAS) is a major physiological regulator of vascular
      tone and is implicated in cardiovascular pathophysiology. More recently, basic
      research has however continuously extended our understanding of the complexicity
      of the systemic and tissular RASs. The peptid hormone, angiotensin II, acts
      primarily via type I (AT1) and type II (AT2) angiotensin receptors. Most, if not
      all, of the peripheral and central actions of angiotensin II, including
      vasoconstriction, renal salt and water retention, facilitation of sympathetic
      transmission, modification of vascular and cardiac structure, oxydative stress
      stimulation and proinflammatory action were all thought to be mediated by the
      angiotensin type 1 receptor, AT1. Angiotensin II/III exerts actions through the
      AT2 receptor, which are directly opposed to those mediated by the AT1 receptor.
      Most notably, proteolytic fragments of angiotensin II also have biological
      activity via ther own receptors: angiotensin-(1-7)/AT1-7 and angiotensin IV/AT4.
      They are vasodilators in many arterial beds. The identification of these
      angiotensins opens the way to develop new therapeutics.

PMID- 15976683
TI  - [Sodium thiosulfate for acute cyanide poisoning: study in a rat model].
AB  - Unlike practices in the United States where it is associated with other
      antidotes, sodium thiosulfate is not used for emergency therapy for cyanide
      poisoning in France. The purpose of this study was to develop a rat model using
      intraperitoneal injections of sodium thiosulfate at a dose of 225 mg/kg to test
      its therapeutic efficacy for acute cyanide poisoning. Efficacy was assessed
      directly by quantifying arterial blood cyanide and indirectly using markers of
      hypoxia: serum lactate and arteriolization of venous blood gases. Cyanide
      poisoning induced intense biological anomalies which were persistent (serum
      lactate) or transient (blood gases). Sodium thiosulfate was found to be an
      effective antidote in the rat enabling rapid normalization of hypoxia markers and
      clearing of cyanide from arterial blood.

PMID- 15976684
TI  - [Development of an intravesial oxybutynin chloride solution: from formulation to
      quality control].
AB  - Intravesical oxybutynin chloride has demonstrated its efficacy in children with
      neurogenic bladder and urinary incontinence refractory to oral anticholinergic
      agents. We developed a 205 microg/ml oxybutynin chloride solution in accordance
      with the specifications of the European Pharmacopeae. To guarantee quality, we
      assessed and validated formulation, the preparation process, and packaging. The
      solution was obtained by disolving oxybutynin chloride in 0.9% saline and sterile
      filtration. The solution was then packaged in syringes. Physical properies for
      intravesical instillation were met: pH 5.76 +/- 0.03, osmolality 281 mosmol/kg.
      The unit dose package guarantees sterility of the solution until use. The
      medication is given by adapting the syringe on the Luer Lock exteremity of the
      urinary catheter. The solution remains stable up to one month at 4 degrees C.

PMID- 15976685
TI  - [Proceedings (Advanced July, October, November, December 2004).]

PMID- 15976686
TI  - [Preparation and administration of cytotoxic drugs: prickly innovation].
AB  - The requirement for safe and optimal administration of cytotoxic drugs led us to
      test a new product manufactured by Codan. The transfer set (CONNECT SET) and the
      administration set (CYTO-AD-SET) were assessed successively by pharmacist
      assistance within a centralized unit for cytotoxic drug preparation and by the
      nursing staff in an ambulatory unit. Transfer sets can be handled in the
      centralized units without using needles, but with an increased sterilization load
      and production cost. Assessment of the administration sets demonstrated time
      saving for the nursing staff. These materials require significant expenditures,
      careful training, and a change in treatment routine, but provide important time
      savings for the nursing staff and considerable improvement in the safety of
      handling cytotoxic drugs.

PMID- 15976688
TI  - [Butyrylcholinesterase: 3D structure, catalytic mechanisms].
AB  - Cholinesterases are the main targets of organophosphorus compounds. Although
      progresses in prophylaxis and treatment of nerve agent poisoning have been
      achieved in the past twenty years, pharmacological protection and emergency
      treatment remain imperfect. All classical pharmacological ways have been explored
      and, the current medical counter-measure arsenal is generally not expected to
      change much. However, the emergence of the catalytic bioscavenger concept has
      aroused new hope. In addition, resolution of the three-dimensional structure of
      human butyrylcholinesterase (BChE) answered some fundamental issues in medical
      defense research: 1) a better description of cholinesterase catalytic mechanisms
      (substrate hydrolysis, inhibition by organophosphorus); 2) aging mechanism of
      phosphylated cholinesterases caused by the dealkylation of branched
      organophosphorous moiety; 3) reasoned site-directed mutagenesis of human BChE
      with the aim of making operational mutants capable of detoxifying
      organophosphorus substrates.

PMID- 15976687
TI  - [Is leptin the missing link between osteoarthritis and obesity?].
AB  - The contribution of leptin, as a possible link between osteoarthritis (OA) and
      obesity, was studied in cartilage and synovial fluid samples obtained from
      osteoarthritic patients. Its effect on cartilage was evaluated in rats after
      intraarticular injections of leptin. Leptin levels were measured in the synovial
      fluid samples by enzyme linked immunosorbent assay; leptin concentrations were
      correlated with the body mass index. Leptin was strongly expressed in osteophytes
      and OA cartilage, while, in normal cartilage, few chondrocytes produced leptin.
      The level of leptin expression was related to the grade of cartilage destruction
      and was in good relation with those of growth factors as IGF1 and TGFb. Studies
      in rats showed that intraarticular leptin injection stimulated anabolic functions
      of chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage
      at both the chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in
      cartilage at both the mRNA and protein levels. In conclusion, leptin may be a
      link between osteoarthritis and obesity, and may play a key role in cartilage
      metabolism. Leptin may contribute to the pathophysiology of OA.

PMID- 15976689
TI  - [Cell therapy product (Dermagen) for treatment of hard-to-heal skin wounds].
AB  - Epidermal sheets were developed for the treatment of hard-to-heal skin wounds.
      Products currently marketed in France, e.g. Epibase, are very efficient but not
      totally satisfactory in cases of very deep dermal injury which often occurs in
      burn victims. A function dermis or "dermis equivalent" association a three
      dimensional matrix (dermal substrate) and allogenic dermal fibroblasts able to
      secrete numerous cytokines, growth factors, and protease inhibitors, was
      developed in our biotechnology laboratory using good manufacturing standards
      (ISO9000). This cell therapy product which is histologically and physiologically
      close to normal dermis is obtained after culturing fibroblasts obtained from a
      microbiologically and virologically validated cell bank for 21 days in a patented
      collagenous sponge. Our laboratories successfully developed a freezing process
      allowing preservation of the product at -80 C. This allows us to perform high
      performance quality control of the batches. The product is easy to use and
      instructions can be described in a few lines. When clinicians order one or more
      Dermagen sheets, depending on the wound area to treat, Dermagen is thawed and
      culturel at 37 C for 48 to 72 hours. Metabolic activity is recovered and the
      product is then packaged in a specific blister with a semi-solid medium to ensure
      good viability during transportation. In some indications, Dermagen acts like a
      true transplant and in others like a biological dressing secreting numerous
      mediators such as growth factors or matrix proteins.

PMID- 15976690
TI  - [Homeopathy and homeopathic medications. Introduction].

PMID- 15976691
TI  - [The technicoregulatory situation in France for manufactured homeopathic
      medications].
AB  - Many homeopathic medications are marketed in France on the basis of old national
      regulations: homeopathic medications with a common denomination (unit or complex
      products) whose former approval was transformed into a marketing authorization in
      1984; "normal formulations" with a special denomination, often dating from before
      1941 (date when drug approval was instituted) including certain produces whose
      marketing approval was obtained under different mechanisms but still sold today.
      After the EEC excluded homeopathic drugs from the "medication" directives, in
      1975 the 92/72/EEC directive stated that beyond the normal requirements for
      quality and safety, the same obligations could not be required for homeopathic
      and allopathic medications. A "registration" system was thus instituted for
      "traditional" medications en lieu of marketing approval. This included a dual
      obligation: 1) abstention from claiming therapeutic indications, 2) avoiding any
      formulation which could carry a risk for the patients (i.e. oral and topical
      formulations exclusive and degree of dilution guaranteeing safety). Beyond this
      restrictive framework, these medications have marketing approval, but, for the
      specific features of homeopathic medications, the directive leaves it up to the
      member States with a "homeopathic tradition" to apply special rules for
      evaluating the results of clinical trials designed to establish safety and
      efficacy. For the efficacy feature, traditional use can be used as an argument
      for marketing approval (article R5143 CSP). In order to create a more rational
      technicoregulatory environment, older products marketed before 1994 are being
      "validated" by group according to a calendar established in 2003 and which should
      run from 2004 to 2012. At the end of this validation procedure, all manufactured
      homeopathic products will either receive marketing approval or be recorder in
      compliance with general or specific European regulations. In conclusion, we make
      a few personal comments which should be helpful for the reader to distinguish
      between therapeutic efficacy and therapeutic interest.

PMID- 15976692
TI  - [Homeopathy confronted with clinical research].
AB  - Homeopathy is a medical practice using medications characterized by four basic
      principles: similitude, dilution, dynamization, and personalization. To date,
      there is no scientific evidence supporting any of these principles. For this
      reason, careful examination of clinical evaluation of homeotherapy trials is the
      only pragmatic way of evaluating the value of the "homeopathic pharmacy". Many
      clinical trials have been conducted over the last decade. Clinical trials are not
      however a prerequisite for marketing these medications since the legal
      authorities do not require proof of efficacy for marketing authorization.
      Unfortunately, these trials which are rarely favorable, often present
      methodological biases which compromise the readability of results and the
      validity of conclusions. Both meta-analyses and individual trials performed in a
      broad spectrum of clinical situations exclude severe disease and do not provide
      data suggesting these products are effective or produce effects reproducible from
      one team to another or over time. For this reason, and at the present state of
      our knowledge, their use cannot be recommended. The public authorities should now
      require the demonstration of efficacy before awarding marketing approval for
      homeopathic medications.

PMID- 15976693
TI  - [Prescription practices: an audit of prescription quality among Lorrain general
      practitioners].
AB  - Better medical practice begins with personal evaluation. A group of Lorraine
      medical practitioners too part in an evaluation of their prescription practices
      and their compliance with existing regulations. The prescription servers as a
      link between the physician, the pharmacists and the patient. Three broad topics
      were studies in this audit: patient identification, regulation per se, and
      general criteria such as legibility and computerization. Among the different
      mandatory inscriptions, the only item which was often missing was the patient's
      age. The results listed here present the average performance observed in a group
      of medical practitioners and the highest and lowest performances.

PMID- 15976694
TI  - A new momentum in the field of transmissible spongiform encephalopathies (TSEs).
AB  - The present work is a critical survey answering a recent paper published by
      Stanley Prusiner's team in Science magazine. The authors claim that they used
      synthetic prions, instead of which they have tailored a particular recombinant
      protein, produced in E. coli, and devoid of its N-terminal part, therefore
      mimicking a truncated protein described by another team who isolated it from an
      iatrogenic TSE patient. This recombinant prion was lethal in normal mice, perhaps
      partly because, contrarily to what happens with the whole-length normal protein,
      these proteins are both neurotoxic, fibrillogenic and insensitive to proteolysis.
      Moreover, an accompanying nucleic acid could explain the infection, because,
      since 1982 and until now, the protein-only hypothesis has never been supported by
      any positive mechanism and experimental proof, and is becoming inadequate.
      Therefore, we have tried to elaborate an alternative hypothesis for the specific
      mechanism of infection in TSE. The transfer of at least a piece of nucleic acid
      from the infecting subject, perhaps the mRNA coding for the truncated protein
      described in human patients, could then reach the corresponding gene in the
      infected subject, where an endogenous reverse transcriptase would be able to
      integrate it. Once altered and stimulated, this last gene could, in turn,
      participate in the generation of nucleic acids able to code the generation of the
      truncated forms of the prion protein.

PMID- 15976695
TI  - [Autologous bone grafts, allografts and biomaterials].

PMID- 15976697
TI  - [Is continued education mandatory or not?].

PMID- 15976698
TI  - [In response to the editorial "Maxillofacial surgery for sale"].

PMID- 15976699
TI  - [Evaluation of sensory deficit of the inferior alveolar nerve after mandibular
      osteotomy].
AB  - INTRODUCTION: Injury of the inferior alveolar nerve (IAN) is one of the most
      common complications of mandibular osteotomy. The wide differences in results
      published to date led us to evaluate the incidence of sensorial disorders
      persisting for one year in a series of 40 patients. MATERIAL AND METHOD: This
      study included 40 patients aged 14-58 years. We studied subjective expression of
      sensorial disorders using a questionnaire with items for the different orofacial
      functions related to the IAN. We studied the clinical expression of these
      sensorial disorders by testing the three modes of exteroceptive sensitivity
      (tact, temperature, pain) in 25 patients. Four clinical tests appropriate for the
      area of the mental nerve. Somesthesic evoked potentials were recorded in 8
      patients. RESULTS: 77% of the patients complained of altered skin sensitivity but
      a sensorial deficit was revealed by clinical tests in only 60%. Somesthesic
      evoked potentials were perturbed for 64% of the nerves with a clinical deficit
      and in 100% without a clinical deficit. DISCUSSION: There was a greater incidence
      of subjective complaints than objective nerve injury. Recoring somesthesic evoked
      potentials provides interesting information for the electrophysiological
      diagnosis of nerve injury. Indications could be widened for traumatic injury of
      the IAN, particularly to obtain medicolegal documentation.

PMID- 15976700
TI  - [Fractures of the mandibular angle: factors predictive of infectious
      complications].
AB  - INTRODUCTION: Fractures of the mandible angle raise the risk of infectious
      complications. We searched for factors predictive of these complications.
      MATERIAL AND METHODS: We reviewed retrospective all cases of mandibular angle
      fracture treated during a 26-month period. We compared two groups: fractures with
      wisdom teeth and fractures without wisdom tooth. For each group we noted clinical
      and radiological characteristics of the fractures and infectious complications.
      RESULTS: The series included 72 mandibular angle fractures, 30 with a wisdom
      tooth against 42 without. Most of the patients were treated within 2 days,
      generally using mini-plate screw fixation. In the wisdom tooth group, 16.6% of
      patients developed infectious complications versus 9.5% in the without wisdom
      tooth group. All patients of the wisdom tooth group presented a potentially
      infectious focus on the preoperative x-rays. For without wisdom tooth group,
      irregular follow-up was found to be the only risk factor. DISCUSSION: The angular
      localization increases the risk of infectious complications especially if the
      wisdom tooth is in the fracture. We propose a decision tree to determine when to
      preserve or not the wisdom tooth.

PMID- 15976701
TI  - [Pre-implantation apposition grafts for edentuous anterior maxillary.
      Retrospective study of 36 patients].
AB  - INTRODUCTION: Apposition grafting is a method of choice for reconstruction of the
      anterior maxillary. The purpose of this work was to evaluate the success rate,
      the degree of bone resorption and the osteointegration of these grafts. MATERIAL
      AND METHODS: We reviewed retrospectively 36 cases of pre-maxillary bone
      apposition in patients operated from 1998 to 2002. Autografts were used for all
      patients. The harvesting site was parietal for 24 patients, intraoral for 8 and
      iliac for 4. RESULTS: There was two graft failures. The success rate was 94.5%.
      Partial resorption with effect on implantation was noted in 3 patients. Eighty
      implants were inserted successfully in 234 grafted sites with on average 2.4
      implants per graft. Three implants were removed. Implant survival was 96.2%.
      DISCUSSION: This study demonstrated that the premaxillary apposition technique
      using autologous grafts provides sufficient bone volume to enable optimal implant
      insertion and stability.

PMID- 15976702
TI  - [Stability of grafts and implants after bone grafting of the maxillary sinus.
      Retrospective analysis of 44 patients].
AB  - OBJECTIVES: We assessed the reliability of maxillary bone grafting and implant
      stability, comparing our results with reports in the literature. MATERIAL AND
      METHODS: This retrospective series included 44 patients who underwent maxillary
      sinus bone grafting between 1998 and 2002. An analogous graft was used for 31
      patients and a combination autologous-bone substitute graft for 13. One hundred
      twelve dental implants were positioned at the grafting site (2.5 implants per
      graft). We assessed recipient site morbidity, bone graft integration and
      stability, and stability of the implants. RESULTS: Bone grafting was successful
      in 97.8% of patients. There was one failure. Two of the 112 implants failed.
      DISCUSSION: Our results are comparable with those in the literature. This study
      demonstrated the reliability of maxillary bone grafting with equivalent results
      using autologous bone and combination autologous bone-bone substitute.

PMID- 15976703
TI  - [Bone graft healing].
AB  - Bone graft healing involves an invasive process where vessels and cells penetrate
      the graft material to enable neoformation of bone. The origin of the material and
      its intrinsic properties and morphology are factors which affect its resorption
      and replacement. The first step involve formation of bone via the osteoconductive
      properties of the graft. For autologous bone, graft resorption enables secondarly
      release of preserved bone proteins, favoring a process of osteo-induction which
      contributes to remodelling and graft replacement by neoformed bone.

PMID- 15976704
TI  - [Disengagement and traction of included canines].

PMID- 15976705
TI  - [Use of hybrid glass ionomere cement for included canines].

PMID- 15976706
TI  - [Gingival fibromatosis associated with cherubism].
AB  - INTRODUCTION: Gingival fibromatosis is frequently an isolated condition, but
      rarely associated with certain illnesses, or uncommon syndromes. CASE: This work
      describes a young patient presenting cherubism, with perturbed consciousness and
      very hyperplastic gingiva covering the major part of the dental crowns.
      DISCUSSION: We recall the characteristic clinical features of cherubism. Outcome
      is generally favorable with regression of the swelling. The combination with
      gingival fibromatosis is a particular manifestation.

PMID- 15976707
TI  - [Multiple metastases of a mandibular ameloblastoma].
AB  - INTRODUCTION: Ameloblastoma is a benign odontogenic tumor which can be locally
      aggressive and invasive. Metastases are rare but possible and must be considered
      as a malignant form of the tumor. OBSERVATION: A 50-year-old woman presented a
      jugal metastasis of a mandibular ameloblastom which had been treated several
      times 28 years earlier. Six months after resection of the metastasis, the patient
      developed multiple cervical node metastases which were removed by radical
      curettage. Five months later, new metastases developed on the scalp and three
      months later a voluminous metastasis involving the right hemiface extended to the
      base of the skull. Surgical resection was only partial followed by radiotherapy.
      Ten months later the outcome was favorable. DISCUSSION: The absence of any
      histological sign of malignity in the primary tumor and in the metastases, as
      observed in our patient, is remarkable. Metastases generally develop in the lung
      (61-80% of cases). Metastases to the scalp have never been described. The time to
      development of a metastasis is generally very long and metastases usually remain
      asymptomatic. Progression is very slow, like for the primary tumor. Several
      factors predictive of metastasis have been described: female gender, age at onset
      of primary tumor (2nd to 3rd decade) and multiple local recurrences. There is no
      standard treatment for metastases. Chemotherapy is not effective. Radiotherapy
      may be effective, particularly when lesions are not accessible to surgery.
      Surgical resection remains the treatment of choice.

PMID- 15976708
TI  - [Oral metastasis of colonic adenocarcinoma].

PMID- 15976709
TI  - [Inflammatory-like cervical tumefaction].

PMID- 15976710
TI  - [Use of autologous platelet concentrates during pre-implantation maxillary
      reconstruction].

PMID- 15976711
TI  - [Study of nasal permeability in patients with operated unilateral clefts].

PMID- 15976712
TI  - [In vivo confocal microscopy evaluation of corneal changes induced after LASIK
      using the IntraLase femtosecond laser technique].
AB  - PURPOSE: To assess stromal modifications occurring after IntraLase femtosecond
      laser for laser in situ keratomileusis (LASIK) using the Heidelberg retina
      tomograph II/Rostock cornea module. MATERIAL AND METHODS: Twelve eyes from six
      patients were examined using the Heidelberg retina tomograph II cornea module
      after IntraLase femtosecond laser: ten eyes were examined at 1 week and 2 months
      after laser surgery, including four eyes examined at day 1, and two eyes examined
      at day 2. Morphological modifications of the corneal stroma, flap interface, and
      flap margin were evaluated at these different times and compared with the
      mechanical microkeratome interfaces of five patients (ten eyes), using the same
      technique at the same periods after the surgical intervention. RESULTS:
      Evaluations at days 1 and 7 showed simultaneous depletion and activation of
      keratocytes on both sides of the interface. We also observed some brightly
      reflecting particles together with scattered, less bright dots, from day 7 and
      increasing after 2 months. Some clinically visible deposits at the level of the
      interface were observed at the periphery of the flap at day 1 and could represent
      cell-degradation products. With confocal microscopy, they appeared as homogeneous
      reflective deposits with a larger size than that of particles; they had decreased
      at month 2. The flap margin appeared microscopically as a very clear-cut edge,
      including epithelial cells, while those performed with a mechanical microkeratome
      appeared more like a poorly limited fibrotic scar. We also observed a secondary
      fibrotic reaction at month 2, adjacent to the still well-defined IntraLase flap
      edge. CONCLUSION: This study showed substantial morphological similarity between
      the interfaces obtained with femtosecond laser and mechanical microkeratome. The
      discovery of brightly reflecting particles in the IntraLase interface goes
      against the hypothesis of the metallic origin of these deposits. The flap margin
      microscopically looked extremely well delimited, but seemed to provoke an
      adjacent secondary fibrotic reaction, both microscopically and macroscopically,
      greater at 2 months than after a mechanical microkeratome cut.

PMID- 15976713
TI  - [Diffuse diabetic macular edema surgery: prospective study of seven cases
      followed up with optical coherence tomography].
AB  - INTRODUCTION: A prospective study was performed in seven eyes of seven
      consecutive patients who had vitrectomy for diffuse diabetic macular edema (DME)
      with ILM premacular delamination as part of this treatment. PATIENTS AND METHODS:
      All patients had retinopathy and DME. Only one patient had previous grid
      photocoagulation. In all eyes, there was no ophthalmoscopic evidence of traction
      from the posterior hyaloid membrane or proliferative tissue, but all patients had
      no posterior vitreous separation. A clinical examination and optical coherence
      tomography (OCT) were performed in preoperative and postoperative surgery (1 and
      6 months). Pars plana vitrectomy with separation of the posterior hyaloid was
      performed in seven cases. RESULTS: Only three patients had vitreomacular traction
      observed on OCT. Statistical analysis revealed a significant decrease in retinal
      thickness 6 months after surgery. Best corrected visual acuity improved in four
      patients. CONCLUSION: Vitreous surgery can improve the visual prognosis of some
      eyes with DME with or without posterior vitreous separation, whether combined or
      not with vitreomacular traction observed on OCT.

PMID- 15976714
TI  - [Antinomic horizontal deviations: esodeviation associated with exodeviation.
      Clinical features and surgery].
AB  - INTRODUCTION: Antinomic deviations are defined as a basic exoposition of the eyes
      associated with innervational convergence excess leading to an esoposition.
      PATIENTS AND METHODS: Thirty-four patients with both exodeviation and
      esodeviation were studied. Surgery consisted in lateral recti (LR) recess with
      fadenoperation on the medial recti. RESULTS: Four types of antinomic deviations
      were found: 1- Primitive exodeviation with an excess of physiological
      accommodative vergences; 2- Consecutive exodeviation due to surgical
      overcorrection of an accommodative esotropia; 3- Infantile exodeviation with
      fixation in adduction, DHD +/- convergence excess; 4- Consecutive infantile
      exodeviation: overcorrection of a congenital esotropia. CONCLUSION: Although
      fadenoperation on the medial recti may seem paradoxical in exodeviations, it is
      the most logical procedure to deal with convergence excess and fixation in
      adduction prevalence. Adjustable sutures for the lateral recti recess appear
      safer and more predictible in these difficult cases.

PMID- 15976715
TI  - [Vitreous hemorrhage in a neonate with galactosemia. A case report].
AB  - Galactosemia is an inherited metabolic disorder due to a defect in one of the
      three enzymes required to fully metabolize the galactose in glucose: the
      galactose 1-phosphate uridyltransferase. Because this enzyme is present in the
      normal foetal liver since the tenth week of gestation, its defect cause
      congenital abnormality due to galactose accumulation, when the mother had taken
      milk during the pregnancy. It is mainly a liver pathology whereas the foetal
      cataract is rare. This latter is usually considered as the sole ophthalmic
      consequence of this disorder but exceptional ocular haemorrhages have also been
      described. We report the case of a neonate with galactosemia free from foetal
      cataract but presenting an unilateral vitreous haemorrhage. Retinal anomalies
      seen after vitrectomy are probably the source of the vitreous blood favoured by
      the coagulopathy associated with the neonatal disease. The causes of infant
      vitreous haemorrhages are often debated and their complications, especially
      severe amblyopia, require vitrectomy within the month following their discovery.
      In galactosemia, vitreous haemorrhage can be prevented by an early diagnosis and
      an appropriate treatment of the liver pathology.

PMID- 15976716
TI  - [Anterior segment necrosis in multidrug-resistant Fusarium keratomycosis: a case
      study].
AB  - Keratomycosis is a rare sight-threatening infection of the cornea, with greater
      morbidity than bacterial keratitis. Predisposing factors in its pathogenesis are
      corneal trauma, mostly of plant origin, and overuse of topical corticosteroids,
      associated or not with antibiotics. We report a case of a 71-year-old man who
      developed Fusarium (lichenicola or solani) keratitis, 15 days after beginning
      topical therapy with a corticosteroid and antibiotic. Despite aggressive
      antifungal therapy with fluconazole, he required a penetrating keratoplasty for
      impending corneal perforation, and finally, even after systemic use of
      itraconazole and topical use of amphotericin B, the infection progressed and an
      evisceration was required. In the evisceration material, a multidrug-resistant
      Fusarium lichenicola or solani, was found, partially sensitive to voriconazole
      only.

PMID- 15976717
TI  - [Bilateral retinal vascular occlusion during antiphospholipid antibody syndrome:
      a case report].
AB  - PURPOSE: Antiphospholipid syndrome is defined by the association of at least one
      clinical event (arterial and/or venous thrombosis, fetal loss) and
      antiphospholipid antibodies. It can be isolated or associated with systemic lupus
      disease. The purpose of this case report is to demonstrate that an ocular
      vascular event can reveal the disease and that its diagnosis is important because
      this disease generally affects young people and may endanger ocular and vital
      prognosis. OBSERVATION: We report the case of a 20-year-old female treated for
      systemic lupus erythematosus for 2 years, who stopped her medical treatment and
      presented a sudden bilateral loss of vision. Fundus examination and fluorescein
      angiography revealed severe bilateral retinal vascular occlusion.
      Antiphospholipid antibody syndrome was confirmed with the presence of
      anticardiolipin antibodies. With medical treatment, there was initially a small
      functional improvement and then a general degradation in 3 months, followed by
      the death of the patient secondary to severe pulmonary emboli. DISCUSSION AND
      CONCLUSION: Central retinal artery or vein occlusion in a young patient must
      suggest the diagnosis of antiphospholipid antibody syndrome. The bilateralism of
      vascular occlusion is considered a severe factor because of its consequence on
      functional ocular and vital prognosis, where it can sound the alarm to the
      extension of thrombotic events to other vessels in the body. Antiphospholipid
      syndrome must be studied in cases of severe retinal vascular occlusion in young
      patients. Its diagnosis is important because the risk of recurrent thrombotic
      events may endanger functional and vital prognosis.

PMID- 15976718
TI  - [Retinal detachment after Excimer laser (myopic LASIK or PRK). A retrospective
      multicentric study: 15 cases].
AB  - INTRODUCTION: Refractive surgery by LASIK or photorefractive keratectomy (PRK)
      generaly aims at a myopic population that has a high probability of developing
      rhegmatogenous retinal detachment (RD). The authors report a multicenter study
      with 15 cases of RD appearing after refractive surgery by Excimer laser and
      discuss the role played by the techniques used. MATERIAL AND METHODS: Five
      centers fitted with nine Excimer laser devices took part in this study. Of 22,700
      eyes undergoing refractive myopic surgery during the period 1994-2002, 15 eyes
      developed rhegmatogenous RD. The average age of the patients with RD was 37
      years. The average myopia was 13.5 D. RD occurred a mean of 20 months after
      refractive laser. RESULTS: Fifteen eyes of 13 patients developed a rhegmatogenous
      RD, two of which were bilateral. Eight of these cases had LASIK surgery and six
      had photorefractive keratectomy; one of the latter patients was retreated with
      LASIK because of substantial regression after PRK. RD was total or subtotal in
      five eyes, partial superior with a temporal tear in six eyes, and nasal in three
      eyes. One case with inferior RD, two cases with giant retinal tear and one case
      with posterior tear were also repaired. Fourteen eyes were suitable for
      operation. The retina was reattached in 12 cases. Mean postoperative visual
      acuity was 7/10. DISCUSSION: The occurrence of rhegmatogenous RD in the myopic
      population is estimated at 2.2%. It is estimated at 0.1% in the emmetropic
      population. The Excimer laser, through its thermic effects, shock wave,
      traumatism undergone by the suction ring at the time of LASIK surgery, could
      increase this risk in myopic patients. A review of the literature cast doubt on
      the cause and effect hypothesis. Personal and multicenter studies (including
      ours) show that the frequency rate of rhegmatogenous RD after Excimer laser is
      equivalent and even lower than that estimated with an emmetropic population. The
      low percentage of RD after Excimer surgery found in the literature as well as in
      our study (<0.1%) may be explained by patient selection, the systematic
      monitoring of the peripheral fundus, and the prophylactic treatment of
      degenerative lesions by photocoagulation. In RD surgery, the cornea must be
      manipulated carefully, a case of flap dehiscence has been reported in the
      literature. CONCLUSION: Refractive surgery by LASIK or PRK for severe myopia
      increases the risk of RD. Systematically monitoring the peripheral fundus and
      preventive photocoagulation have mitigated its occurrence, and the risk incurred
      in the myopic population has fallen to the emmetropic population's rate.
      Nevertheless, candidates for LASIK or PRK surgery must be informed because severe
      myopia constitutes a non-negligible risk factor.

PMID- 15976719
TI  - [An in vivo OCT study of human natural accommodation in a 19-year-old albino].
AB  - Modifications of the anterior segment during accommodation of the eye under
      examination cannot be studied in a simple and direct way with anterior segment
      imaging techniques such as Scheimpflug photography, A Scan, B Scan, and UBM. With
      this equipment, it is necessary to stimulate the fellow eye in order to observe
      the variations of the analyzed eye. The techniques using ultrasound equipment can
      only be used with contact systems or with water baths that will modify the
      anatomical dimensions or the pressure of the anterior segment. With the
      Scheimpflug photographic technique, geometrical reconstructions are necessary and
      cannot be used in certain axes. Optical coherence tomography provides the
      advantage of producing non-contact images of the anterior segment in static and
      dynamic conditions that are then easy to use. The target of the optical system
      can be focused and unfocused with negative or positive lenses, thus reproducing
      the conditions of natural accommodation. With a normal subject, the morphological
      modifications of the crystalline lens behind the iris screen cannot be studied
      because the infrared light source used is blocked by the pigment epithelium. The
      absence of this pigment in an albino subject allowed us to study the
      modifications of the crystalline lens and the ciliary body during accommodation.
      In this study, we were able to definitely confirm all the modifications of the
      anterior segment as described by von Helmholtz in 1855, who, at the time, used
      very rudimentary optical procedures based on the reflections of a flame on the
      surface of the crystalline lens.

PMID- 15976720
TI  - [KID syndrome: pathogenesis of ocular lesions].
AB  - KID is a rare ectodermal syndrome of unknown etiology. It is characterized by
      vascular keratitis (K), congenital ichthyosis (I) and neurosensorial deafness
      (D). We report the cases of three patients with KID syndrome who all had typical
      vascular keratitis responsible for photophobia and impaired visual acuity, and
      severe meibomian dysfunction associated with hyperkeratotic lid borders. The
      authors believe that meibomian dysfunction plays an important role in the
      pathogenesis of ocular lesions. Consequently, patients were treated with oral
      minocycline, topical steroids and artificial tears. This treatment proved to
      significantly reduce ocular discomfort.

PMID- 15976721
TI  - [Dragged disc syndrome in a patient presenting neurofibromatosis type II: a case
      study].
AB  - We report a case of dragged disc syndrome associated with neurofibromatosis type
      II (NF2). A 5-year-old girl with amblyopia (right eye, 20/200; left eye, 20/40)
      presented with dragged disk syndrome and a posterior subcapsular cataract in the
      left eye associated with an epiretinal membrane in the right eye. Five years
      later, she developed exophthalmos in the right eye associated with a cervical
      mass. MRI revealed schwannoma developing in the left optic nerve sheath
      associated with a cervicothoracic schwannoma. The child was diagnosed with NF2.
      Association of posterior subcapsular cataract with macular epiretinal membranes
      is highly suggestive of NF2, although the dragged disk syndrome has not been
      previously reported in NF2 to our knowledge. It may also be an ocular feature of
      this disease.

PMID- 15976722
TI  - [Bilateral uveitis in relapsing polychondritis. A case report].
AB  - We report a rare ocular manifestation of relapsing polychondritis. A 28-year-old
      woman presented with a 5-year history of relapsing polychondritis with chondritis
      of the nose, ears and tracheobronchial system. The ocular symptoms were bilateral
      uveitis with macular involvement and papillaedema. Ocular manifestations of
      relapsing polychondritis occur in 60% of patients. Uveitis is a rare symptom,
      sometimes severe, which can lead to blindness. This case report with a literature
      review sheds light on the features of this disease.

PMID- 15976723
TI  - [Can Xylocaine gel be used as a cataract anesthetic?].

PMID- 15976724
TI  - [Advantages and disadvantages of the femtosecond laser microkeratome].
AB  - Laser in situ keratomileusis (LASIK) complications are mainly attributable to
      imperfect cutting with the mechanical microkeratome. The femtosecond laser is an
      important challenger because it can provide extremely precise cutting beginning
      at any corneal point. We analyze the potential of this new tool from the results
      reported in the literature. The optomechanical control of the impact position
      provides freer and more effective intrastromal cutting than the blade. The best
      cutting matrix is obtained with the postage stamp method. If the plasma quality
      is not perfectly under control, side effects such as tissue streaks and secondary
      ultraviolet radiations can be observed. For LASIK surgery, femtolaser cutting can
      offer greater safety, reproducibility, predictability and flexibility. The risk
      of incomplete or irregular cutting and the free cap risk are reduced. Striae,
      epithelial defects and interface deposits should be minimized. A better flap
      congruence can limit the risk of secondary displacement and epithelial ingrowth.
      The results of making thinner flaps should be more predictable. Other than the
      high cost of the procedure, laser cutting has very few disadvantages. In 1999,
      Intralase Corporation introduced the first femtolaser microkeratome on the
      American market. Approximately 120,000 intra-LASIK procedures have been carried
      out with fewer cutting complications than with the mechanic blade.

PMID- 15976725
TI  - [New etiological concepts in uveitis].
AB  - Uveitis remains an important cause of visual impairment, particularly in young
      patients. Idiopathic forms of intraocular inflammation should no longer be
      regarded as a presumed clinical entity, and the ophthalmologist must reconsider
      the specific etiology of primary uveitis when the clinical examination does not
      yield a definitive diagnosis or when the course of the disease on corticosteroids
      remains atypical. Laboratory tests based on serum analysis have limited value and
      should not be considered as diagnostic proof in different clinical presentations.
      The diagnostic management of infectious uveitis has been greatly improved by the
      use of molecular techniques applied to ocular fluids and tissues. Polymerase
      chain reaction (PCR) technology is a powerful tool that should be proposed in
      atypical cases of uveitis or retinitis of unclear but potentially infectious
      origin. This strategy is a major step before using unconventional and new
      immunomodulatory agents such as anti-TNF-alpha molecules. Under strict
      experimental conditions including adequate testing to rule out a possible
      contamination, PCR and its variants have changed our practical approach to
      intraocular inflammatory disorders and have provided new details for the
      understanding of infectious uveitis. The concept of pathogen-induced intraocular
      inflammation can be revisited in the light of molecular data obtained after
      anterior chamber paracentesis or diagnostic vitrectomy.

PMID- 15976726
TI  - [News on therapies for uveitis].
AB  - The immunosuppression required for the treatment of uveitis can be achieved
      through conventional agents or through the use of specific modulators of
      inflammation. Whatever the choice, it is important to limit side effects: by
      restricting access to certain drugs in patients presenting a high risk of
      complications (tuberculosis screening before using Remicade), reducing side
      effects through preventive measures (use of alendronates during oral
      corticotherapy), or choosing a local delivery route (intraocular triamcinolone).
      Intraocular triamcinolone has certain beneficial characteristics such as high
      local dosage without systemic effect. However, it can cause a pressure rise in
      10% to 20% of patients. It requires certain precautions when given to prevent
      development of a pseudo-endophthalmitis. Remicade is a novel synthetic
      immunosuppressant directed against TNF-alpha. This chimeric antibody can be
      useful in the treatment of severe uveitis that is unresponsive to conventional
      therapy. It is currently being tested in clinical trials in uveitis both in
      Europe and the USA.

PMID- 15976728
TI  - [Diabetes and optic disk edema].

PMID- 15976727
TI  - [ISO 9001-2000 certification for refractive laser treatment].
AB  - PURPOSE: To obtain ISO 9001-2000 certification for laser corneal refractive
      treatment, never before sought in Europe. MATERIAL AND METHODS: The consulting
      firm Veritas led the certification process with the clinic's staff manager. This
      ISO norm is dedicated to the implementation of a quality management system. We
      assessed and optimized all necessary resources, evaluating customer satisfaction
      using patient and referring-physician surveys. We started quality rounds
      including surgeons, nurses, and technicians. Based on this preparation, we
      redefined and explained all processes including staff responsibilities and
      necessary resources in the quality manual. The procedure lasted 14 months with
      substantial involvement on the part of the management. RESULTS: Unconditional ISO
      9001-2000 certification was granted by the independent audit firm, BVQI, in
      december 2003 for refractive laser treatment. CONCLUSION: The 2000 version of the
      new ISO 9001-2000 seeks to meet the demand for improving health care delivery in
      this field, most particularly by establishing a clear procedural orientation.
      Such certification enhances team work, stabilizes methodologies, and reinforces
      cohesion and self-audit. Patients notice that the center follows a consistent
      quality policy and are assured that the clinic respects rules and regulations.
      Certification is an advantageous alternative when accreditation cannot be
      considered. Our article discusses the steps taken in upper management, quality
      management, procedural guidance, as well as customer and staff counselling. It
      also discusses the project's cost/benefit ratio for the organization.

PMID- 15976729
TI  - Differentiating constrictive pericarditis from restrictive cardiomyopathy.
AB  - Constrictive pericarditis and restrictive cardiomyopathy are 2 forms of diastolic
      dysfunction with similar presentation but different treatment options. Whereas
      constrictive pericarditis has the potential of being cured with pericardiectomy,
      restrictive cardiomyopathy is usually incurable. It is therefore crucial to
      differentiate between the 2 disorders. In the last few years, new diagnostic
      techniques have become available to differentiate these causes of diastolic
      dysfunction from each other. This review provides a complete, in-depth comparison
      of the 2 disorders with regard to their symptoms and clinical features, etiology,
      pathophysiology, hemodynamics, echocardiographic presentation, and finally the
      different available management options.

PMID- 15976730
TI  - The no-reflow phenomenon: epidemiology, pathophysiology, and therapeutic
      approach.
AB  - Over the past 20 years, advances in the management of ST segment elevation
      myocardial infarction have focused on the rapid achievement of patency in the
      infarct-related artery. The limitation of this therapeutic strategy has been
      exposed with the development of diagnostic techniques to assess coronary
      microcirculation, including myocardial contrast echo, magnetic resonance imaging,
      myocardial perfusion grading, and the coronary flow wire. These methods have
      expanded our ability to understand and recognize the no-reflow phenomenon, which
      describes the absence of tissue perfusion despite epicardial coronary artery
      patency and flow. Although the mechanisms responsible for the development of no
      reflow are not fully understood, the end result is microvascular damage produced
      by microvascular obstruction or reperfusion injury. Ideally, early recognition of
      the no-reflow phenomenon should provide an opportunity for therapeutic
      intervention designed to augment tissue perfusion and maintain the viability of
      myocardium at risk. A number of pharmacologic agents are being used in
      conjunction with percutaneous transluminal coronary angioplasty in an attempt to
      improve microvascular perfusion. These include IIb/IIIa receptor antagonists,
      adenosine, verapamil, and the experimental agent nicorandil. In the new
      millennium, the emphasis of reperfusion therapy is being shifted downstream from
      its exclusive focus on the epicardial artery to assuring normal blood flow at the
      tissue level. This article will review the epidemiology, pathophysiology, and
      therapeutic approach to this vexing clinical problem.

PMID- 15976731
TI  - The proinflammatory and hypercoagulable state of diabetes mellitus.
AB  - The diabetic population is at high risk for development of cardiovascular disease
      (CVD), cerebrovascular disease, and peripheral vascular disease. Approximately
      80% of these patients die from a thrombotic cause, with CVD complications being
      involved in 75% of those. The mechanisms involved in the development of coronary
      artery disease (CAD) in the diabetic population are multifactorial, including
      hyperglycemia, hyperlipidemia, hypertension, and insulin resistance, ultimately
      leading to endothelial dysfunction and accelerated atherogenesis. Thus, diabetes
      has become a CAD risk equivalent. Early and aggressive intervention in treating
      risk factors may reduce the risk of developing diabetes and may prevent CVD in
      patients with established diabetes.

PMID- 15976733
TI  - Percutaneous left ventricular assist device in acute myocardial infarction and
      cardiogenic shock.
AB  - Despite advances in coronary angioplasty for acute myocardial infarction (MI),
      the mortality rate for patients presenting with cardiogenic shock remains high.
      This case review describes the management of a patient with a non-ST segment
      elevation MI complicated by cardiogenic shock. The clinical and therapeutic
      utility of a percutaneous left atrial-to-femoral arterial ventricular assist
      device is discussed.

PMID- 15976734
TI  - Patients at risk. Tricuspid regurgitation and survival.

PMID- 15976735
TI  - Atherosclerosis. Bigger is better: high-density and low-density lipoprotein
      particle size.

PMID- 15976736
TI  - Vascular disease and erectile dysfunction.

PMID- 15976737
TI  - Primary and secondary treatment for Helicobacter pylori in the United States.
AB  - One of every 4 to 5 patients who receives antimicrobial therapy for Helicobacter
      pylori will not have successful eradication. Antimicrobial resistance, poor
      compliance with the antibiotic regimen, and drug-related side effects all play a
      role in determining the outcome of therapy. This article discusses the issues
      involved in H. pylori eradication, the mechanism of antibiotic delivery to the
      mucus layer of the stomach, and primary and secondary treatment strategies for H.
      pylori in the United States.

PMID- 15976738
TI  - Role of extracorporeal shock wave lithotripsy in the treatment of pancreatic
      stones.
AB  - Calcifications in chronic pancreatitis are usually the result of chronic
      inflammation or altered metabolism. Calcifications can perpetuate the cycle of
      ductal obstruction and contribute to pain, worsening of pancreatic inflammation,
      ductal disruption, and deterioration of the exocrine and endocrine function of
      the gland. Removal of pancreatic duct calculi can reduce pain and improve
      glandular function. Purely endoscopic stone removal has limited success, because
      of stone location, burden, and presence of strictures in the pancreatic duct.
      Extracorporeal shock wave lithotripsy (ESWL) allows fragmentation of stones
      refractory to endoscopic methods and facilitates spontaneous stone passage or
      endoscopic removal. Among the various forms of lithotripters, none is clearly
      superior to the others. Current data suggest that ESWL is effective in complete
      duct clearance in up to 50% of patients and in duct decompression and symptomatic
      improvement in up to 70% of patients. ESWL should be considered as a useful
      adjunctive tool in the treatment of pancreatic duct calculi.

PMID- 15976739
TI  - Environmental versus genetic risk factors for irritable bowel syndrome: clinical
      and therapeutic implications.
AB  - The pathogenesis of irritable bowel syndrome (IBS) has traditionally been based
      on the biopsychosocial model that emphasizes that the symptom manifestations of
      IBS and consulting behavior are influenced at least in part by psychological
      processes. However, there has been increasing interest in trying to identify and
      unravel potential molecular mechanisms in IBS, and this endeavor has been driven
      by some evidence that there is a true genetic contribution to IBS. IBS does
      aggregate in families, and the concordance of IBS is twice as great in
      monozygotic compared with dizygotic twins in most, but not all, studies. A number
      of genetic polymorphisms have been associated with IBS but most remain to be
      independently confirmed, and unknown gene-environment interactions probably
      remain essential for the disorder to manifest. As we become better able to
      specify the phenotypes within IBS, it seems likely that increasingly relevant
      gene associations that have implications for testing and treatment will rapidly
      be identified. IBS probably represents a collection of several organic diseases,
      some of which may have a genetic component; the biopsychosocial model, although
      important, may represent a gross oversimplification of the underlying molecular
      pathogenesis.

PMID- 15976740
TI  - Adefovir dipivoxil: focus on its use in the treatment of chronic hepatitis B.
AB  - Adefovir is classified as a nucleotide reverse transcriptase inhibitor because it
      acts by inhibiting hepatitis B virus DNA polymerase (reverse transcriptase) and
      causing DNA chain termination after its incorporation into the viral DNA.
      Adefovir dipivoxil is indicated for the treatment of chronic hepatitis B in
      adults with evidence of active viral replication and either evidence of
      persistent elevations in serum aminotransferases (alanine [ALT] or aspartate
      [AST]) or histologically active disease. It is useful in the treatment of
      patients with either hepatitis B e antigen-positive or -negative chronic
      hepatitis B. The recommended adefovir dipivoxil dose in the treatment of chronic
      hepatitis B in patients with adequate renal function is 10 mg once daily.
      Adefovir dipivoxil therapy can reduce viral load, improve ALT, and produce
      histologic improvement in patients with chronic hepatitis B. Improvements are
      generally seen within the first few weeks of therapy and have shown persistence
      up to at least 3 years with continued therapy. Therapy with adefovir dipivoxil is
      generally well tolerated. However, nephrotoxicity is a risk with adefovir
      therapy, especially in patients receiving higher doses (30-120 mg/d). Patients
      should have their renal function monitored closely throughout therapy and may
      require an adjustment in dose relative to changes in the creatinine clearance.
      Lactic acidosis and severe hepatomegaly with steatosis may also occur during
      therapy.

PMID- 15976742
TI  - Treatment of chronic hepatitis C in patients coinfected with human
      immunodeficiency virus and hepatitis C virus.

PMID- 15976743
TI  - Inflammatory bowel disease: a new combination therapy for pouchitis.

PMID- 15976744
TI  - Endoscopic therapy for gastroesophageal reflux disease--new data.

PMID- 15976746
TI  - Role of antibiotics in the management of hepatic encephalopathy.
AB  - This article explores the rationale for use of antibiotics in the treatment of
      hepatic encephalopathy, discusses the role of antibiotics relative to other
      therapeutic approaches, and considers the reasons that limit the use of the
      antibiotics most commonly prescribed for the management of hepatic encephalopathy
      in the United States. Although the scientific rationale for the use of
      antibiotics in hepatic encephalopathy is well founded, the clinical evidence for
      their benefits is rather limited. There is no doubt that many antibiotics cause a
      decrease in intraluminal production of ammonia. However, the commonly prescribed
      antibiotics are also associated with a variety of adverse effects. None of the
      antibiotics typically used for hepatic encephalopathy is adequately tolerated in
      the target patient population. The clinical evidence to date does not support the
      first-line use of currently available antibiotics in the treatment of hepatic
      encephalopathy. To improve upon current antibiotic offerings for hepatic
      encephalopathy, an antibiotic should provide broad-spectrum coverage against both
      aerobic and anaerobic bacteria, effectively control neuropsychiatric signs and
      symptoms, and be extremely well tolerated in the target population. An antibiotic
      fulfilling these criteria would constitute an advance in therapy for hepatic
      encephalopathy.

PMID- 15976747
TI  - Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic
      encephalopathy: antimicrobial activity, efficacy, and safety.
AB  - The nonabsorbed (< 0.4%) oral antibiotic rifaximin, which has been available for
      enteric bacterial conditions for more than a decade in several countries outside
      the United States, was recently introduced in the United States for the treatment
      of travelers' diarrhea, and is being evaluated in clinical trials for possible
      introduction for hepatic encephalopathy and other conditions involving enteric
      bacteria. This article discusses the antimicrobial activity, efficacy, and safety
      of rifaximin in hepatic encephalopathy. Rifaximin is a nonsystemic antibiotic
      with antibacterial activity against enteric pathogens for gastrointestinal
      infections. In 15 studies, several of which were adequately powered to assess
      efficacy, rifaximin was at least as effective as lactulose/lactitol (the current
      mainstay of pharmacologic treatment for hepatic encephalopathy) and neomycin and
      paromomycin (the antibiotics most commonly prescribed for hepatic encephalopathy)
      in improving neurologic signs and symptoms and reducing blood ammonia levels. The
      results of studies employing small samples are similar to those of the larger
      studies. Finally, rifaximin has a good tolerability profile in patients with
      hepatic encephalopathy, and thus appears to constitute a promising new option for
      this disorder. The current database on rifaximin would be strengthened by results
      of placebo-controlled studies to quantify more precisely the benefits of therapy.

PMID- 15976755
TI  - Some realism about informed consent.

PMID- 15976756
TI  - More realism about informed consent.

PMID- 15976757
TI  - Specific detection of Flt3 point mutations by highly sensitive real-time
      polymerase chain reaction in acute myeloid leukemia.
AB  - Among activating class III receptor tyrosine kinase (Flt3) mutations, internal
      tandem duplications of Flt3 (Flt3-ITD) are detected in about 25% of patients with
      acute myeloid leukemia (AML). In contrast, mutations within the tyrosine kinase
      domain of Flt3 (Flt3-TKD mutations) are less frequent (approximately 7%), and
      there are only limited data on the frequency of recently demonstrated activating
      Flt3 point mutation at codon 592 (Flt3-V592A mutation). We evaluated a new
      approach for rapid screening of Flt3-TKD and Flt3-V592A mutations using the
      fluorescence resonance energy transfer (FRET) principle in a group of 122
      patients. Based on individual Flt3-TKD mutations, we designed patient-specific
      primers to perform a highly sensitive polymerase chain reaction (PCR) assay for
      rapid detection of minimal residual disease (MRD). We also used a model system
      with MonoMac-6 cells carrying the Flt3-V592A mutation to establish a mutation
      specific real-time PCR approach also for this molecular aberration. We identified
      9 cases (8%) of Flt3-TKD mutations (5 cases of mutation D835Y, 3 cases of
      mutation D835H, and 1 case of mutation Del836), and no cases of Flt3-V592A
      mutation. Screening for Flt3-TKD mutations with fluorescent probes is equivalent
      to conventional screening using standard PCR followed by EcoRV restriction. We
      present a real-time PCR protocol that can be used for MRD analyses based on
      individual Flt3-TKD mutations. Examples of MRD analyses are presented for all 3
      subtypes of Flt3-TKD mutation identified in this study. In summary, we
      demonstrate new methodological approaches for rapid screening of Flt3 point
      mutations and for detection of MRD based on patient-specific Flt3-TKD mutations.

PMID- 15976758
TI  - Comparison of 3 automated assays for C-reactive protein in end-stage renal
      disease: clinical and epidemiological implications.
AB  - Chronic inflammation has been repeatedly reported in individuals undergoing
      hemodialysis. C-reactive protein (CRP) is considered a marker of chronic
      inflammation, as well as a mediator of the atherosclerotic process. Clinical and
      epidemiologic studies are based on plasma values obtained with the use of various
      automated methods. Our aim was to test 3 commercially available methods and
      compare the values obtained with the use of these tests in a population of
      individuals undergoing hemodialysis. We compared the following methods:
      immunoturbidimetry (AU2700 biochemistry analyzer; Olympus, Rungis, France) laser
      nephelometry (Behring Diagnostics, Marburg, Germany), and nephelometry (Beckman
      Instruments, Fullerton, Calif. The 3 methods were used in 3 different centers:
      Montpellier, France; and Pisa and Turin, Italy, respectively. We prepared samples
      for the estimation of imprecision values (ie, coefficient of variation [CV]) from
      the plasma of normal patients by adding purified C-reactive protein at
      concentrations ranging from 2.6 to 180 mg/L for intraassay variation and
      concentrations of 0, 1, 2, 3, 5, 10, 20, 50, 100, 150, and 180 mg/L for
      interassay variation. Intraassay imprecision was determined with the use of 10
      replicate analyses on the same sample of the same day. We assessed interassay
      imprecision using the same sample, divided into aliquots and measured on 5
      consecutive days. Agreement between methods was assessed on predialysis serum
      samples collected from patients with stable chronic kidney disease who were
      undergoing long-term hemodialysis at the 3 different centers (Montpellier,192;
      Pisa, 56; Turin,98). Serum was separated from the red cells and stored in 3
      aliquots at -70 degrees C until it could be analyzed. Samples were thawed only
      once, circulated among the 3 centers, and each tested with all 3 of the methods.
      The Beckman method yielded the most precise results, with intraassay CVs ranging
      from 1 to 2 and interassay CVs ranging from 1 to 4. The Behring method was the
      least precise, with intraassay and interassay CVs ranging from 12 to 15 and 7 to
      16, respectively. The results of the Olympus method fell between those of the
      other 2 methods. Agreement between the results of the Olympus and Behring methods
      was satisfactorily. The Beckman and Olympus methods yielded, on average, similar
      results over the entire range of CRP values. We detected significant disagreement
      between the Beckman method and the other 2 methods, obtaining results 10 to 100
      times lower with the Beckman method. This became evident in terms of kappa
      statistics. Our findings emphasize the need for careful assessment of the methods
      used to detect CRP in serum samples. Failure to do so may ultimately have a
      negative impact on the real relevance of CRP as a marker and on the role of
      chronic implication particularly in epidemiologic studies.

PMID- 15976759
TI  - Comparison of modified Thrombelastograph and Plateletworks whole blood assays to
      optical platelet aggregation for monitoring reversal of clopidogrel inhibition in
      elective surgery patients.
AB  - Clinically monitoring recovery from clopidogrel and nonsteroidal anti
      inflammatory drug (NSAID) inhibition requires whole blood assays corresponding to
      a standard methodology such as platelet-rich plasma aggregation monitored
      optically (OPA). We compared OPA, using an ED 50 dose of adenosine diphosphate
      activation, with 2 whole blood assays, Plateletworks (PWA) and modified
      Thrombelastograph (TEG). Two sets of assays were performed on 43 surgery patients
      while on clopidogrel and off clopidogrel to determine the reversal of absolute
      and relative inhibition. The modified TEG had Spearman correlations with OPA for
      absolute (rho = .424; P = .006) and relative inhibition (rho = .742; P < .0001).
      PWA correlations with OPA gave absolute (rho = .28; P = .08) and relative
      inhibition (rho = .46; P = .004) values. Bland-Altman analysis indicated
      agreement of both tests with OPA, showing constant biases of about 18% and some
      dependency on mean magnitude error. Cohen effect size thresholds defined
      nonresponders as < 7.7% clopidogrel inhibition relative to baseline recovery of
      full platelet function. Apparent nonresponse to clopidogrel or lack of platelet
      recovery did not correlate with statin or NSAID therapies. These PWA and modified
      TEG whole blood assays could prove useful for monitoring the reversal of
      clopidogrel and NSAID inhibition before surgery. More important, these assays
      done at baseline and after beginning clopidogrel therapy could monitor the
      effectiveness for the individual patients with cardiovascular disease and help
      identify the need for alternative therapies.

PMID- 15976760
TI  - Epigallocatechin-3-gallate, a green-tea polyphenol, suppresses Rho signaling in
      TWNT-4 human hepatic stellate cells.
AB  - Epigallocatechin-3-gallate (EGCG), a major constituent of the polyphenoids in
      green tea, has been reported to possess a wide range of biologic activities,
      including antifibrogenesis. Activated hepatic stellate cells (HSCs) are central
      to hepatic fibrosis, and Rho (a small GTPase)-signaling pathways have been
      implicated in the activation and proliferation of HSCs. In this study, we
      investigated the effect of EGCG on Rho-signaling pathways in activated human HSC
      derived TWNT-4 cells. EGCG inhibited stress-fiber formation, an indicator of Rho
      activation, and changed the distribution of alpha-smooth-muscle actin. These
      inhibitory effects of EGCG were restored by overexpression of constitutively
      active Rho. A pull-down assay revealed that activated Rho (GTP-bound state) was
      strongly inhibited by ECGC and accompanied by suppressed phosphorylation of focal
      adhesion kinase, which is a regulator of Rho-signaling pathways. 5-Bromo-2'-deoxy
      uridine incorporation demonstrated that ECGC (100 micromol/L suppressed cell
      growth by 80%, and terminal deoxynucleotidyl transferase viotin-deoxyruidine
      triphosphate nick end-labeling revealed that EGCG (100 micromol/L) caused
      apoptosis in half of the total cells. EGCG also strongly inhibited
      lysophoaphatidic acid (an activator of Rho) and induced phosphorylation of
      mitogen-activated protein kinases (Erk1/2, c-jun kinase, and p38). These findings
      demonstrate that EGCG regulates the structure and growth of HSCs by way of Rho
      signaling pathways and suggest that EGCG has therapeutic potential in the setting
      of liver fibrosis.

PMID- 15976761
TI  - Effect of influenza vaccine on markers of inflammation and lipid profile.
AB  - Despite wide use of the influenza vaccine, relatively little is known about its
      effect on the measurement of inflammatory markers. Because inflammatory markers
      such as C-reactive protein (CRP) are increasingly being used in conjunction with
      lipids for the clinical assessment of cardiovascular disease and in epidemiologic
      studies, we evaluated the effect of influenza vaccination on markers of
      inflammation and plasma lipid concentrations. We drew blood from 22 healthy
      individuals 1 to 6 hours before they were given an influenza vaccination and 1,
      3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte
      chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha,
      and serum amyloid A were measured, and differences in mean concentrations of
      absolute and normalized values on days 1, 3, and 7 were compared with mean
      baseline values. There was a significant increase in mean IL-6 (P < .01 absolute
      values, P < .001 normalized values) on day 1 after receiving the influenza
      vaccine. The mean increases in normalized high sensitivity CRP values were
      significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in
      normalized serum amyloid A was significant only on day 1 (P < .05). No
      significant changes were seen in mean concentrations of IL-2 soluble receptor
      alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the
      lipids, significant decreases in mean concentrations of normalized triglyceride
      values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after
      vaccination. Our findings show that the influenza vaccination causes transient
      changes in select markers of inflammation and lipids. Consequently, clinical and
      epidemiologic interpretation of the biomarkers affected should take into account
      the possible effects of influenza vaccination.

PMID- 15976762
TI  - About the cover illustration: Thea sinensis - the common tea plant.

PMID- 15976769
TI  - Morpheus, god of sleep or god of death?

PMID- 15976770
TI  - Enhancing reperfusion therapy for myocardial infarction with dual antiplatelet
      therapy: Breaking the glass ceiling.

PMID- 15976771
TI  - A perspective on the potential cardioprotective benefits of periodontal therapy.
AB  - In recent years, the concepts of the pathogenesis of atherosclerosis and
      cardiovascular events have broadened from a lipid-centric view of etiology to the
      appreciation of the importance of the inflammatory processes. Although obesity,
      oxidized lipids, and other factors are known to contribute to cardiovascular
      inflammation, the role of infection is believed to serve as a critical
      inflammatory stimulus that contributes to both atherogenesis and acute events via
      plaque destabilization. This inflammatory process can involve the vasculature
      directly by interaction of the organisms or bacterial by-products with the vessel
      wall or indirectly via modulation of hemostasis or hepatic activation of the
      acute phase response that leads to increased circulating levels of acute-phase
      reactants such as C-reactive protein (CRP). Epidemiological studies have
      suggested a significant moderate association between periodontal infection and
      cardiovascular risk adjusting for traditional risk factors. The potential role of
      periodontal disease as a possible chronic source of infection and inflammation is
      supported by findings indicating an association of periodontal disease with
      elevated serum CRP and interleukin 6. Recently, periodontal therapy studies have
      shown a lowering of CRP and interleukin 6, and in this issue, a new report of an
      improvement of endothelial function, as measured by flow-mediated dilation. These
      studies raise the possibility that periodontal disease may represent a modifiable
      risk factor that merits further study.

PMID- 15976772
TI  - Acute coronary syndrome statistics: what you don't see can hurt you.

PMID- 15976773
TI  - Rate control versus rhythm control: choose your poison.

PMID- 15976774
TI  - Which role for multislice computed tomography in clinical cardiology?

PMID- 15976775
TI  - Should we aggressively treat elderly patients with cardiogenic shock?

PMID- 15976776
TI  - Genetic association studies in cardiology.
AB  - The last decade has witnessed the emergence of the genetic association study into
      the mainstream clinical literature. Technological advances and the Human Genome
      Project have resulted in widespread interest in exploring these new variables in
      clinical disease. Although the concept of relating genetic variation to disease
      is exciting, this excitement must be tempered by the many limitations of such
      analyses. Here we offer a perspective piece on genetic association studies in
      cardiology. We begin with a fundamental research and clinical interest-linking
      genes with disease. We then concentrate the body of the article on the
      statistical aspects of these studies that are often overlooked or
      underemphasized. We then use specific examples from the literature to illustrate
      some of our statistical considerations. We then focus on the distinction between
      association and causation and conclude with perspectives on how this field of
      study may move forward in a productive manner.

PMID- 15976777
TI  - The biology, utilization, and attenuation of C-reactive protein in cardiovascular
      disease: part I.

PMID- 15976778
TI  - The biology, utilization, and attenuation of C-reactive protein in cardiovascular
      disease: part II.

PMID- 15976779
TI  - Practical considerations of beta-blockade in the management of the post
      myocardial infarction patient.
AB  - Acute myocardial infarction (AMI) is a major cause of death and disability in the
      United States that affects an estimated total of 1.5 million men and women each
      year. Despite significant advances in pharmacologic and interventional therapies,
      25% of men and 38% of women still die within 1 year of the acute event. Beta
      blockers have been shown to significantly decrease the risk of morbidity and
      mortality in patients after an AMI. National guidelines recommend that all
      patients with AMI may be started on beta-blocker therapy and continued
      indefinitely, unless absolutely contraindicated or not tolerated. However, a
      substantial portion of eligible AMI survivors are not prescribed beta-blockers in
      the hospital after an acute event or upon hospital discharge. In addition,
      patients with AMI are often treated with agents whose long-term use has not been
      shown effective and for which optimal dosing has not been defined. This paper
      will discuss the background of beta-blocker use for the treatment of AMI, discuss
      the rationale for choosing specific agents, and present protocols for initiating
      or switching to evidence-based therapies.

PMID- 15976780
TI  - The early glycoprotein IIb/IIIa inhibition in non-ST-segment elevation acute
      coronary syndrome (EARLY ACS) trial: a randomized placebo-controlled trial
      evaluating the clinical benefits of early front-loaded eptifibatide in the
      treatment of patients with non-ST-segment elevation acute coronary syndrome-
      study design and rationale.
AB  - BACKGROUND: The recent North American and European practice guidelines in
      patients with non-ST-segment elevation acute coronary syndrome (nSTE ACS)
      recommend glycoprotein IIb/IIIa (GpIIb-IIIa) inhibition in patients undergoing an
      early invasive treatment strategy. However, the guidelines are not explicit
      regarding the timing of initiation of GpIIb-IIIa antagonists, and there is marked
      variation in clinical practice regarding their use. STUDY DESIGN: The EARLY ACS
      trial will enroll 10,500 patients in a prospective, randomized, double blind,
      international, multicenter investigation of early eptifibatide compared with
      placebo (with provisional eptifibatide in the catheterization laboratory) in
      patients with high-risk nSTE ACS in whom an invasive strategy is planned no
      sooner than the next calendar day. The primary efficacy end point is the 96-hour
      composite of all-cause mortality, nonfatal myocardial infarction, recurrent
      ischemia requiring urgent revascularization, or need for thrombotic bailout with
      GpIIb-IIIa inhibitor during percutaneous coronary intervention. The key secondary
      end point is the composite of death or nonfatal myocardial infarction within 30
      days of enrollment. IMPLICATIONS: The EARLY ACS trial will be the largest study
      to date to evaluate the utility of early GpIIb-IIIa inhibition in patients with
      nSTE ACS in whom an invasive approach is planned. This trial will provide
      important evidence regarding the benefit of initiating eptifibatide early after
      presentation with high-risk ACS versus delayed provisional use after coronary
      angiography. Furthermore, it will explore the ability of biomarkers to identify
      high-risk patients who may benefit from such an early aggressive approach.

PMID- 15976781
TI  - Development of a multicenter peripheral arterial interventional database: the PVD
      QI2.
AB  - BACKGROUND: The number of peripheral vascular intervention (PVI) procedures
      performed is steadily increasing in the United States. PVD-QI 2 is a prospective,
      multicenter observational study designed to improve the quality of care for
      patients undergoing PVI and to better understand the effectiveness and
      appropriateness of PVI in improving outcomes of peripheral arterial disease. The
      registry aims to elucidate which comorbid conditions and procedure-related
      variables are associated with beneficial or adverse outcomes after vascular
      interventions. METHODS: Five centers are currently prospectively collecting data
      on consecutive PVIs performed at their institutions and will include patients
      with both claudication and critical limb ischemia. A common data collection form
      and a standard set of definitions were developed during several planning
      meetings. Information on patient demographics, clinical history, comorbid
      conditions, treatment approaches, and in hospital outcomes are being collected.
      Patients will be followed up at 30 days, 6 months, and 1 year after each
      procedure to identify recurrent vascular events, medication use, lifestyle
      modifications (regular exercise, dietary modification), self-reported walking
      scores, and mortality. Data validity will be assured through review of data form
      accuracy by a trained nurse, by automatic database diagnostic routines, and by
      site visits that include review of angiography suite logs and randomly selected
      charts. CONCLUSIONS: The development of a quality-controlled PVI registry
      requires the commitment and collaboration of clinician-investigators and hospital
      systems devoted to understanding factors that contribute to quality outcomes.
      Central to achievement of this goal is the creation of a careful diagnostic and
      data quality assessment system. This registry will provide important clinical
      insights into patient demographic and clinical characteristics, procedural
      characteristics, and current practice patterns that foster or impede achievement
      of long-term quality-based clinical outcomes for patients with peripheral
      arterial disease.

PMID- 15976782
TI  - Highlights from the American College of Cardiology Annual Scientific Session
      2005: March 6 to 9, 2005, Orlando, Florida.

PMID- 15976783
TI  - Implantable cardioverter defibrillators and cardiac resynchronization therapy in
      patients with left ventricular dysfunction: randomized trial evidence through
      2004.
AB  - Although many studies have shown that implantable cardioverter defibrillator
      (ICD) therapy improves the survival of patients with significant left ventricular
      dysfunction, the magnitude of effectiveness of ICD therapy in clinically defined
      subgroups remains uncertain. Similarly, although studies have shown an
      improvement in patients' hemodynamics and quality of life with cardiac
      resynchronization therapy (CRT), there is a continuing uncertainty about the
      effect of CRT on patients' survival and the magnitude of improvement in quality
      of life with this therapy. On August 24, 2004, an ad hoc group of experts
      representing clinical cardiovascular medicine, biostatistics, economics, and
      health policy were joined by representatives of the Food and Drug Administration,
      Centers for Medicare and Medicaid Services (Baltimore, Md), Agency for Healthcare
      Research and Quality (Rockville, Md), and the device industry for a 1-day round
      table to review the available clinical trial evidence on the effect of ICD
      therapy in the primary prevention of sudden cardiac death and the effect of CRT
      in patients with congestive heart failure. The meeting was organized by the Duke
      Clinical Research Institute, Durham, NC, and funded in part by the Agency for
      Healthcare Research and Quality. This document summarizes the evidence reviewed
      at that meeting and the discussions of that evidence.

PMID- 15976784
TI  - Should we routinely supplement coronary patients with folate therapy to prevent
      in-stent restenosis?

PMID- 15976785
TI  - Effect of clopidogrel plus aspirin on tissue perfusion and coronary flow in
      patients with ST-segment elevation myocardial infarction: a new reperfusion
      strategy.
AB  - BACKGROUND: Current reperfusion strategies may fail to achieve optimal tissue
      perfusion in ST-elevation myocardial infarction (STEMI). We investigated the
      effect of clopidogrel plus aspirin on tissue perfusion and coronary flow in
      infarct patients treated with fibrinolytic agents. METHODS: Consecutive 78
      patients with STEMI were randomized to receive clopidogrel plus aspirin
      (clopidogrel group, n = 42) or placebo plus aspirin (placebo group, n = 36)
      before streptokinase. Maximum and total ST-segment resolutions (sumSTR) were
      calculated at 90 minutes after fibrinolysis. TIMI flow grade and corrected TIMI
      frame count in infarct-related artery were evaluated at predischarge. Inhospital
      ischemic and hemorrhagic events were also analyzed. RESULTS: Baseline
      characteristics were comparable in both groups. Both mean maximum ST-segment
      resolution (54.5 +/- 21.3% vs 44.6 +/- 22.0%, P = .047 ) and sumSTR (52.7 +/-
      21.1% vs 42.8 +/- 20.7%, P = .041) were slightly higher in the clopidogrel group
      than placebo group. The rate of complete sumSTR 70% was significantly higher in
      the clopidogrel group compared with placebo group (31% vs 11%, P = .021). TIMI
      flows were similar in both groups, but corrected TIMI frame count was
      significantly lower in the clopidogrel group compared with placebo group (25.5 +/
      10.5 vs 33.5 +/- 11.8 frames, P = .027). Clinical events were comparable in 2
      groups; however, there were 1 death caused by heart failure and moderate bleeding
      in the clopidogrel group. CONCLUSION: Our results suggest that clopidogrel plus
      aspirin compared with aspirin alone may improve myocardial tissue perfusion and
      coronary flow in STEMI patients receiving streptokinase.

PMID- 15976786
TI  - Association of intravenous morphine use and outcomes in acute coronary syndromes:
      results from the CRUSADE Quality Improvement Initiative.
AB  - BACKGROUND: Although intravenous morphine is commonly used for the treatment of
      chest pain in patients presenting with non-ST-segment elevation acute coronary
      syndromes (NSTE ACS), its safety has not been evaluated. The CRUSADE Initiative
      is a nonrandomized, retrospective, observational registry enrolling patients with
      NSTE ACS to evaluate acute medications and interventions, inhospital outcomes,
      and discharge treatments. METHODS: The study population comprised patients
      presenting with NSTE ACS at 443 hospitals across the United States from January
      2001 through June 2003 (n = 57,039). Outcomes were evaluated in patients
      receiving morphine versus not and between patients treated with morphine versus
      intravenous nitroglycerin. RESULTS: A total of 17,003 patients (29.8%) received
      morphine within 24 hours of presentation. Patients treated with any morphine had
      a higher adjusted risk of death (odds ratio [OR] 1.48, 95% CI 1.33-1.64) than
      patients not treated with morphine. Relative to those receiving nitroglycerin,
      patients treated with morphine also had a higher adjusted likelihood of death (OR
      1.50, 95% CI 1.26-1.78). Utilizing a propensity score matching method, the use of
      morphine was associated with increased inhospital mortality (OR 1.41, 95% CI 1.26
      1.57). The increased risk of death in patients receiving morphine persisted
      across all measured subgroups. CONCLUSIONS: Use of morphine either alone or in
      combination with nitroglycerin for patients presenting with NSTE ACS was
      associated with higher mortality even after risk adjustment and matching on
      propensity score for treatment. This analysis raises concerns regarding the
      safety of using morphine in patients with NSTE ACS and emphasizes the need for a
      randomized trial.

PMID- 15976787
TI  - Periodontal treatment improves endothelial dysfunction in patients with severe
      periodontitis.
AB  - BACKGROUND: Because epidemiological studies provide evidence that periodontal
      infections are associated with an increased risk of progression of cardiovascular
      and cerebrovascular disease, we postulated that endothelial dysfunction, a
      critical element in the pathogenesis of atherosclerosis, would be present in
      patients with periodontal disease. METHODS: We tested endothelial function in 30
      patients with severe periodontitis and 31 control subjects using flow-mediated
      dilation (FMD) of the brachial artery. The groups were matched for age, sex, and
      cardiovascular risk factors. Three months after periodontal treatment, including
      both mechanical and pharmacological therapy, endothelial function was reassessed
      by brachial artery FMD. Markers of systemic inflammation were measured at
      baseline and at follow up. RESULTS: Flow-mediated dilation was significantly
      lower in patients with periodontitis than in control subjects (6.1% +/- 4.4% vs
      8.5% +/- 3.4%, P = .002). Successful periodontal treatment resulted in a
      significant improvement in FMD (9.8% +/- 5.7%; P = .003 compared to baseline)
      accompanied by a significant decrease in C-reactive protein concentrations (1.1
      +/- 1.9 vs 0.8 +/- 0.8 at baseline, P = .026). Endothelium-independent nitro
      induced vasodilation did not differ between the study groups at baseline or after
      periodontal therapy. CONCLUSION: These results indicate that treatment of severe
      periodontitis reverses endothelial dysfunction. Whether improved endothelial
      function will translate into a beneficial effect on atherogenesis and
      cardiovascular events needs further investigation.

PMID- 15976788
TI  - Acute coronary syndrome national statistics: challenges in definitions.
AB  - BACKGROUND: Increasing convergence in the management of acute myocardial
      infarction (AMI) and unstable angina (UA) has led some to consider whether these
      2 diagnoses should be consolidated into acute coronary syndrome (ACS) for the
      purpose of coronary heart disease surveillance. METHODS: We used the 1988-2001
      Nationwide Inpatient Sample, which has demographic and diagnosis data on 6 to 7
      million discharges per year from a sample of US nonfederal hospitals. We
      identified discharges with a first- or all-listed diagnosis of AMI (
      International Classification of Diseases, Ninth Revision, Clinical Modification
      410) or UA (International Classification of Diseases, Ninth Revision, Clinical
      Modification 411) and defined ACS-first as a primary diagnosis of either
      condition and all-listed ACS as codes 410 or 411 among any diagnoses. Sampling
      weights were applied to produce yearly national discharge estimates; annual
      population estimates were used to calculate yearly hospital discharge rates;
      rates were then adjusted to the 2000 standard population. RESULTS: Rates of first
      and all-listed AMIs changed little. Rates of first-listed UA fell 87% from
      29.7/10,000 in 1988 to 3.9/10,000 in 2001. This sharp decline was seen among all
      age and sex groups. Consequently, rates of ACS as a primary diagnosis declined
      44%. In contrast, discharge rates for all-listed UA and ACS declined only
      modestly. CONCLUSIONS: As a primary diagnosis, UA is disappearing. Rates of first
      listed ACS are quite sensitive to the decline in UA. Although discharge data
      based on first-listed diagnoses have been used to estimate the national incidence
      of AMI, they may not provide accurate data regarding current trends for ACS.

PMID- 15976789
TI  - Urinary tract infection in patients with acute coronary syndrome: a potential
      systemic inflammatory connection.
AB  - BACKGROUND: Inflammation has been linked with atherosclerotic disease development
      and instability. Contributors to systemic inflammation, such as subclinical
      infection, may trigger acute coronary syndromes (ACSs). METHODS: Using a case
      control study design, we evaluated the prevalence of urinary tract infection
      (UTI) among 100 consecutive ACS patients, compared with a contemporary control
      group undergoing elective coronary artery bypass graft (CABG) surgery. Cases were
      excluded if ACS was not confirmed by chart review or if a urinalysis was not
      obtained <or=6 hours of arrival. Patients excluded from the control group were
      those with myocardial infarction (MI) within 21 days before CABG or without a pre
      CABG urinalysis. RESULTS: The case and control groups were well matched, with the
      only significant differences being less congestive heart failure (OR 7.3, 95% CI
      3.3-15.9) and more prior MI (OR 0.5, 95% CI 0.3-0.9) in the CABG control group.
      UTI was present in 27 of the ACS cases and 11 of the controls. Among ACS case
      patients, those with UTI tended to be older and more often women, with more
      diabetes, hyperlipidemia, hypertension, and renal insufficiency, and more
      commonly had non-ST elevation MI. In unadjusted analysis, UTI was 3 times more
      common in the cases versus controls (OR 3.0, 95% CI 1.4-6.4); results were
      similar after multivariable adjustment (OR 3.0, 95% CI 1.3-6.8). CONCLUSIONS:
      Subclinical UTI is common among patients with ACS. Underlying infection may
      precipitate ACS via activation of systemic inflammation. This hypothesis should
      be explored in other data sets, and similar relationships with other bacterial
      and viral infections should be examined.

PMID- 15976790
TI  - Ethnic differences in cardiovascular risk factor burden among middle-aged women:
      Study of Women's Health Across the Nation (SWAN).
AB  - BACKGROUND: We evaluated ethnic differences in the 10-year risk of myocardial
      infarction or coronary death derived from Framingham risk equation and in a
      composite measure of emerging cardiovascular disease risk factors in women and
      whether statistical adjustments for educational attainment, geographic location,
      and lifestyle attenuated the magnitude of the ethnic differences in risk.
      METHODS: Two thousand eight hundred thirty-four premenopausal women free of
      stroke, heart disease, or diabetes and aged of 42 to 52 years (1400 whites, 729
      African American, 226 Hispanic, 231 Chinese, and 248 Japanese) had measurements
      of blood pressure, lipids and lipoproteins, waist circumference, glucose,
      insulin, lipoprotein(a), fibrinogen, factor VII, plasminogen activator inhibitor,
      tissue-type plasminogen activator antigen, and high-sensitivity C-reactive
      protein. Framingham risk score and number of risk factors in the top quartile of
      the distribution of risk factors not included in the Framingham score (called
      composite burden) were calculated. RESULTS: The unadjusted mean values for the
      two summary scores were higher among African Americans and Hispanics than other
      groups. Statistical adjustments for education and geographical site accounted for
      a majority of the ethnic differences, with an additional small effect of
      lifestyle for the composite burden score. Largest ethnic differences were
      apparent for waist circumference, lipoprotein(a), high-sensitivity C-reactive
      protein, and untreated blood pressure. CONCLUSIONS: A substantial part of the
      risk associated with ethnicity can be attributed to socioeconomic status and
      geographical location. As the ethnic composition of the United States population
      becomes more diverse, it is important to appreciate the cardiovascular disease
      risk factor burden present in some minority groups.

PMID- 15976791
TI  - Racial differences in reperfusion therapy use in patients hospitalized with
      myocardial infarction: a regional phenomenon.
AB  - BACKGROUND: Racial differences in reperfusion therapy use among patients
      hospitalized with myocardial infarction (MI) have been previously reported as
      national phenomenon. However, it is unclear whether racial differences in
      treatment vary by region. METHODS: Using data from the National Registry of
      Myocardial Infarction-2 and -3, a cohort of patients hospitalized with MI in the
      United States between 1994 and 2000, we sought to determine whether racial
      differences in reperfusion therapy use varied by geographic region in patients
      eligible for reperfusion therapy with no clinical contraindications to treatment
      (n = 204 230). RESULTS: Black patients had lower crude rates of reperfusion
      therapy than white patients (66.5% vs 69.9%, -3.3% racial difference, 99% CI 
      4.4% to -2.2%) overall. However, racial differences in reperfusion therapy use
      varied by geographic region. Reperfusion therapy rates were similar for black
      patients and white patients in the Northeast (67.9% black vs 65.3% white, +2.7%
      racial difference, 99% CI -0.5% to 5.8%) and statistically comparable for
      patients in the Midwest (68.3% black vs 69.0% white, -0.7% racial difference, 99%
      CI -2.9% to 1.5%) and West (70.7% black vs 72.6% white, -1.9% racial difference,
      99% CI -5.1% to 1.2%). Racial differences in reperfusion therapy use were
      greatest for patients hospitalized in the South (64.5% black vs 71.7% white, 
      7.1% racial difference, 99% CI -8.7% to -5.6%). Racial differences were reduced,
      but geographic variations in racial differences persisted after multivariable
      adjustment. CONCLUSIONS: Lower rates of reperfusion therapy use among black
      patients with MI do not reflect a national pattern of racial differences in
      treatment, but a practice pattern predominantly attributable to the South.

PMID- 15976792
TI  - Indications for angiography subsequent to coronary artery bypass grafting.
AB  - BACKGROUND: Postoperative myocardial infarction is a rare, but potentially severe
      complication after coronary artery bypass grafting (CABG). Early markers for
      coronary bypass graft failure or native vessel occlusion are required, because
      immediate intervention could prevent major myocardial damage. METHODS: One
      thousand patients with coronary artery disease consecutively underwent CABG.
      Postoperative coronary angiography was performed in 40 patients with suspected
      myocardial ischemia. Creatine kinase (CK), CK-MB, leukocyte count, C-reactive
      protein (CRP), lactate dehydrogenase (LDH), and glutamate-oxalacetate
      transaminase (GOT) were assessed at 0, 6, 12, 24, 48, and 72 hours after CABG as
      well as 12-lead standard electrocardiography (ECG). RESULTS: Postoperative
      angiography of 40 patients with suspected myocardial infarction revealed graft
      failure or occluded native vessels in 13 (32.5%) individuals. Patients with graft
      or vessel occlusion presented elevated (P < .005) leukocyte counts (17,215 +/-
      6632 vs 10,773 +/- 3902 G/L) immediately after CABG. CK-MB concentrations
      differed ( P < .05) at 6 hours after CABG (54 +/- 48 vs 30 +/- 18 U/L). CK, CRP,
      LDH, and GOT did not show any differences between both groups. Frequency of ECG
      ST-segment elevation was increased (P < .05) in ischemic patients (69.2% vs
      29.6%). CONCLUSIONS: Common signs of myocardial ischemia usually allow to
      diagnose unstable angina or myocardial infarction under native conditions. In
      contrast, these criteria frequently fail after CABG. Combined diagnostic criteria
      of elevated leukocytes (>14,000 G/L, at hour 0) and either ST elevation or CK-MB
      concentrations >35 U/L (at hour 6) at least seem to be very useful in detecting
      myocardial infarction after bypass grafting. In parallel, CK-MB elevation (>70
      U/L, at hour 6) alone seems to predict ischemia. Both criteria should indicate
      angiography and potential revascularization. If these conditions were not
      fulfilled, the risk of perioperative myocardial infarction appears to be
      moderate.

PMID- 15976793
TI  - Behavior of both epicardial and intramural coronary artery flow velocities in
      various models of myocardial hypertrophy: role for left ventricular outflow tract
      obstruction.
AB  - BACKGROUND: The assessment of coronary flow velocity is becoming crucial in the
      diagnosis and management of several cardiac dysfunctions and conventional Doppler
      echocardiography is currently the technique most widely used for detecting their
      abnormalities noninvasively. METHODS: We sought to evaluate the differences in
      coronary flow velocity using conventional transthoracic Doppler echocardiography,
      measuring both the left anterior descending and such intramural (IM) coronary
      arteries' flow, among the following 4 categories of patients with myocardial
      hypertrophy: group A, obstructive hypertrophic cardiomyopathy (n = 12); group B,
      nonobstructive hypertrophic cardiomyopathy (n = 10); group C, left ventricular
      hypertrophy (LVH) due to hypertension (n = 10); and group D, LVH due to aortic
      valve stenosis (n = 10). RESULTS: No significant difference between the 4 groups
      was found with respect to the left anterior descending velocity. Diastolic peak
      (P < .01) and mean (P < .05) velocities in the IM arterioles were significantly
      higher in patients from groups A and D than in groups B and C. At multivariate
      analysis, both dynamic (group A) and fixed (group D) systolic peak gradients,
      measured by continuous wave Doppler sampling through the left ventricular (LV)
      outflow tract or the aortic valve, respectively, were found to be major
      determinants of the IM diastolic velocity, independently on the LV mass. About
      75% of patients with obstructive hypertrophic cardiomyopathy showed IM peak and
      mean velocity >100 cm/s and >70 cm/s, respectively (P = .005). CONCLUSION: These
      findings likely suggest [corrected] a role for the LV systolic obstruction within
      the intricate adaptive mechanisms of coronary blood flow to LVH.

PMID- 15976794
TI  - Benign outcome in a long-term follow-up of patients with hypertrophic
      cardiomyopathy in Brazil.
AB  - BACKGROUND: Selected patients with hypertrophic cardiomyopathy (HCM) have 3% to
      4% annual mortality as compared to only 0.5% to 1.5% in nonselected patients. Our
      aim was to evaluate survival and prognostic factors in HCM in patients in a
      tertiary care center. METHODS: From 1980 to 1997, 214 patients were prospectively
      studied, with a mean follow-up of 7 years (range 1-25 years); there were 102 male
      and 112 female patients, aged 37 +/- 16 years (range 3-76 years). All patients
      had 12-lead electrocardiogram, 24-hour Holter monitor, and surface
      echocardiography. Univariate analysis was performed for known adverse factors
      such as young age, family history, syncope, functional class, atrial
      fibrillation, ventricular hypertrophy, left ventricular outflow tract
      obstruction, and nonsustained ventricular tachycardia. RESULTS: There were 22
      deaths (10%), 15 directly related to HCM (sudden in 11). The cumulative survival
      rates were 94.5% at 5 years, 91% at 10 years, and 87.9% at 15 years. The annual
      mortality rate was 1%. Only New York Heart Association functional class III/IV
      and maximal ventricular wall thickness >30 mm were associated with HCM-related
      cardiac death. CONCLUSIONS: We concluded that even a referred population of HCM
      patients may have a relatively benign outcome. Prognosis is related to advanced
      functional class and degree of left ventricular hypertrophy.

PMID- 15976795
TI  - Rate control versus rhythm control for patients with persistent atrial
      fibrillation with mild to moderate heart failure: results from the RAte Control
      versus Electrical cardioversion (RACE) study.
AB  - BACKGROUND: This study was conducted to compare rate- and rhythm-control therapy
      in patients with persistent atrial fibrillation (AF) and mild to moderate chronic
      heart failure (CHF). Rate control is not inferior to rhythm control in preventing
      mortality and morbidity in patients with AF. In CHF, this issue is still
      unsettled. METHODS: In this predefined analysis of the RACE study, a total of 261
      patients were in New York Heart Association (NYHA) classes II and III at
      baseline. These patients were analyzed. The primary end point was a composite of
      cardiovascular mortality, hospitalization for CHF, thromboembolic complications,
      bleeding, pacemaker implantation, and life-threatening drug side effects.
      Furthermore, quality of life was compared. RESULTS: After 2.3 +/- 0.6 years, the
      primary end point occurred in 29 (22.3%) of the 130 rate-control patients and in
      32 (24.4%) of the 131 rhythm-control patients. More cardiovascular deaths,
      hospitalization for CHF, and bleeding occurred under rate control. Thromboembolic
      complications, drug side effects, and pacemaker implantation were more frequent
      under rhythm control. Quality of life did not differ between strategies. In
      patients successfully treated with rhythm control, the prevalence of end points
      was not different from those who were in AF at study end. However, the type of
      end point was different: mortality, bleeding, hospitalization for heart failure,
      and pacemaker implantation occurred less frequently. CONCLUSIONS: In patients
      with mild to moderate CHF, rate control is not inferior to rhythm control.
      However, if sinus rhythm can be maintained, outcome may be improved. A
      prospective randomized trial is necessary to confirm these results.

PMID- 15976796
TI  - Multislice spiral computed tomographic angiography of coronary arteries in
      patients with suspected coronary artery disease: an effective filter before
      catheter angiography?
AB  - BACKGROUND: Despite impressive image quality, it is unclear if noninvasive
      coronary angiography with multislice spiral computed tomography (CT) is powerful
      enough to act as a filter before invasive angiography (INV-A) in symptomatic
      patients. METHODS AND RESULTS: We therefore studied 133 consecutive symptomatic
      patients with suspected coronary artery disease (CAD) and an indication for INV-A
      (chest pain and signs of ischemia in conventional stress tests). Patients with
      known CAD, acute coronary syndrome, or a calcium volume score >1000 were
      excluded. In all patients, both INV-A and multislice CT angiography (MSCT-A)
      (Philips MX 8000 multislice spiral CT, scan time 250 milliseconds, slice
      thickness 1.3 mm, 120 mL of contrast agent, 4 mL/s, retrospective gating) were
      directly compared by 2 independent investigators using the American Heart
      Association 15-segment model. Altogether, we studied 1596 segments, 74% had
      diagnostic image quality. Multislice CT angiography correctly identified 68
      significant stenoses of the 75 stenoses seen with INV-A (sensitivity 91%). In 945
      of 1185 diagnostic segments, stenosis could correctly be ruled out with MSCT-A.
      There were 3 times more stenoses seen with MSCT-A compared with INV-A (positive
      predictive value 29%) mainly because of misclassification of nonobstructive
      plaques as stenosis. The per-patient analysis allowed to exclude significant CAD
      in 42 (32%) of 133 patients. In only 6 of 53 patients, MSCT-A failed to detect
      significant stenosis, 4 of those were in small segments not requiring
      intervention. Calcium scoring alone was less suited as a filter before
      angiography: 25 patients (18% of study group) had a calcium score = 0, and 8 of
      these patients turned out to have significant stenoses. CONCLUSION: Multislice CT
      angiography, but not calcium scoring alone, offers promise to reduce the number
      of INV-A in symptomatic patients with suspected CAD by up to one third with
      minimal risk for the patient.

PMID- 15976797
TI  - Noninvasive evaluation of pericardial effusion composition by computed
      tomography.
AB  - BACKGROUND: Measurement of the hematocrit (HCT) and total protein (TP) of
      pericardial fluid can be of critical importance in the management of pericardial
      effusion (PE) but requires pericardiocentesis. There has been no systematic study
      of computed tomography (ct) hounsfield density (hd) measurement for the
      noninvasive evaluation of pe composition. METHODS: We performed CT-guided
      pericardiocentesis in 53 patients to obtain simultaneous measurement of the PE
      HD, HCT, and TP. We determined the relationship of PE HCT to the following
      variables: (1) the average of the mean HD in 5 regions of interest (ROIs) within
      the PE; (2) the maximum PE HD; (3) the difference between the average effusion
      region of interest HD and the ventricular blood pool HD. We also correlated PE HD
      with PE HCT and TP to assess their contribution to the PE CT HD. RESULTS: The
      average of the HD measured in up to 5 regions within the PE was the best
      predictor of PE HCT ( r = 0.84). Addition of ventricular blood pool HD and venous
      HCT to the regression did not improve prediction of PE HCT over average PE HD
      alone. Pericardial effusion HD was unrelated to PE TP. There was a statistically
      significant difference in the PE HD among 8 categories of underlying disease
      etiology in the population. Excluding postcardiotomy cases (n = 22) in which PE
      etiology is known before pericardiocentesis, visceral or vascular rupture was
      associated with the highest HD values. Hounsfield density >30 HU had a
      sensitivity of 100%, specificity 70%, and predictive value 33% for this condition
      in the remaining cases (n = 31). CONCLUSIONS: Computed tomography is a rapid and
      accurate method for noninvasive estimation of pericardial fluid HCT and may be
      helpful in guiding both the acute management and differential diagnosis of PE.

PMID- 15976798
TI  - Outcome of patients aged >or=75 years in the SHould we emergently revascularize
      Occluded Coronaries in cardiogenic shocK (SHOCK) trial: do elderly patients with
      acute myocardial infarction complicated by cardiogenic shock respond differently
      to emergent revascularization?
AB  - BACKGROUND: In the SHOCK trial, the group of patients aged >or=75 years did not
      appear to derive the mortality benefit from early revascularization (ERV) versus
      initial medical stabilization (IMS) that was seen in patients aged <75 years. We
      sought to determine the reason for this finding by examining the baseline
      characteristics and outcomes of the 2 treatment groups by age. METHODS: Patients
      with cardiogenic shock (CS) secondary to left ventricular (LV) failure were
      randomized to ERV within 6 hours or to a period of IMS. We compared the
      characteristics by treatment group of patients aged >or=75 years and of their
      younger counterparts. RESULTS: Of the 56 enrolled patients aged >or=75 years,
      those assigned to ERV had lower LV ejection fraction at baseline than IMS
      assigned patients (27.5% +/- 12.7% vs 35.6% +/- 11.6%, P = .051). In the elderly
      ERV and IMS groups, 54.2% and 31.3%, respectively, were women ( P = .105) and
      62.5% and 40.6%, respectively, had an anterior infarction (P = .177). The 30-day
      mortality rate in the ERV group was 75.0% in patients aged >or=75 years and 41.4%
      in those aged <75 years. In the IMS group, 30-day mortality was 53.1% for those
      aged >or=75 years, similar to the 56.8% for patients aged <75 years. CONCLUSIONS:
      Overall, the elderly randomized to ERV did not have better survival than elderly
      IMS patients. Despite the strong association of age and death post-CS, elderly
      patients assigned to IMS had a 30-day mortality rate similar to that of IMS
      patients aged <75 years, suggesting that this was a lower-risk group with more
      favorable baseline characteristics. The lack of apparent benefit from ERV in
      elderly patients in the SHOCK trial may thus be due to differences in important
      baseline characteristics, specifically LV function, and play of chance arising
      from the small sample size. Therefore, the SHOCK trial overall finding of a 12
      month survival benefit for ERV should be viewed as applicable to all patients,
      including those >or=75 years of age, with acute myocardial infarction complicated
      by CS.

PMID- 15976799
TI  - Effects of abciximab and preprocedural glycemic control in diabetic patients
      undergoing elective coronary stenting.
AB  - BACKGROUND: In diabetic patients, the combination of abciximab with stenting has
      been demonstrated to be the standard of care to reduce target vessel
      revascularization (TVR) and mortality. Moreover, a preprocedural hyperglycemia
      has been associated with a higher rate of TVR after an elective stent
      implantation. We sought to evaluate the effects of abciximab and/or preprocedural
      glycemic control on 30 and 180 days of TVR and on 1-year major adverse cardiac
      events (MACE-cardiac mortality, TVR, and myocardial infarction) in diabetic
      patients undergoing elective coronary stenting. METHODS: From January 2002
      through May 2003, diabetic patients undergoing elective stenting of de novo
      coronary artery lesions were randomized to abciximab or placebo infusion.
      Preprocedural hyperglycemia was defined as fasting plasma glucose >or=126 mg/dL
      (7.0 mmol/L) immediately before the procedure. RESULTS: A total of 122
      consecutive patients with diabetes (62.4 +/- 10.2 years, 80 men) were enrolled in
      the study. Sixty-nine (56.5%) were randomly assigned to receive abciximab (34
      with and 35 without preprocedural hyperglycemia) and 53 (43.5%) to placebo (23
      with and 30 without hyperglycemia). Target vessel revascularization was
      significantly lower in diabetic patients who received abciximab at 30 days (2.9%
      and 2.8% vs 8.7% and 6.6% in nonabciximab group with or without hyperglycemia,
      respectively, P < .01) but not at 6 months (31.4% and 26.5% vs 30% and 28.7%, P =
      NS). Conversely, the cumulative incidence of MACE was significantly higher among
      diabetic patients with preprocedural hyperglycemia (64.7% and 65.2%) versus
      diabetic patients with preprocedural glycemic control (37.1% and 40%), treated
      with or without abciximab, respectively (P < .05). CONCLUSIONS: A preprocedural
      hyperglycemia is associated with a higher rate of MACE, regardless of the use of
      abciximab, in diabetic patients undergoing elective coronary stenting.

PMID- 15976800
TI  - ST-segment elevation resolution and outcome in patients treated with primary
      angioplasty and glucose-insulin-potassium infusion.
AB  - BACKGROUND: To evaluate the impact of adjunctive high-dose glucose-insulin
      potassium (GIK) on ST-segment elevation resolution in patients with ST-segment
      elevation myocardial infarction (MI). METHODS: As part of a randomized controlled
      trial of GIK versus no GIK in patients treated with primary percutaneous coronary
      intervention (PCI) for ST-elevation MI in a tertiary referral center, we analyzed
      ST-segment elevation resolution. Paired electrocardiographic recordings (baseline
      and 3 hours after primary PCI) were available in 612 (65%) of 940 patients.
      RESULTS: We analyzed paired electrocardiograms of 310 patients randomized to GIK
      and 302 control patients. Baseline characteristics of the groups were comparable.
      Combined complete (>70%) and partial (30%-70%) resolution was more commonly
      observed in the GIK group (87%) when compared with the control group (78%), odds
      ratio 1.92 (95% CI 1.23-3.02, P = .004); 1-year mortality was lower in patients
      with combined complete and partial resolution compared with patients without
      resolution (3.8% vs 10.3%, P = .011). There was no difference in 1-year mortality
      between GIK and control patients (5.5% vs 4.3%, P = .58). CONCLUSIONS: In
      patients with ST-elevation MI treated with primary PCI, addition of GIK is
      associated with improved ST-segment elevation resolution. ST-segment elevation
      resolution is related to improved 1-year survival. No benefit of GIK on 1-year
      outcome was observed. Future trials should investigate whether GIK-induced
      improvement of ST-segment elevation resolution results in more favorable clinical
      outcome.

PMID- 15976802
TI  - Embolic protection during saphenous vein graft intervention using a second
      generation balloon protection device: results from the combined US and European
      pilot study of the TriActiv Balloon Protected Flush Extraction System.
AB  - BACKGROUND: Stent placement in saphenous vein bypass grafts is associated with a
      high incidence of myonecrosis usually resulting from embolization of thrombus and
      friable atheroma. Embolic protection devices reduce the incidence of adverse
      events after vein graft stenting. However, first-generation balloon occlusion
      systems are still associated with a 10% incidence of periprocedural adverse
      events. We report the first experience with a new second-generation balloon
      occlusion embolic protection device, the TriActiv Balloon Protected Flush
      Extraction System. METHODS: Ninety-six lesions in 78 saphenous vein grafts were
      treated in 74 patients. The primary end point was major adverse cardiovascular
      events at 30 days. RESULTS: Device success was achieved in 92% of patients, and
      atheromatous debris was recovered in 69% of analyzed aspirates. By 30 days, major
      adverse cardiovascular events, which were limited to non-Q-wave myocardial
      infarctions, occurred in 16.2%. Per protocol analysis in patients with device
      success revealed a rate of adverse events of only 5.7%. CONCLUSIONS: The initial
      experience with the TriActiv Balloon Protected Flush Extraction System
      demonstrated a high success rate and recovery of embolic debris with an
      acceptable rate of adverse events. A large randomized trial will compare this
      device to other embolic protection systems.

PMID- 15976803
TI  - Early effects of statin therapy on endothelial function and microvascular
      reactivity in patients with coronary artery disease.
AB  - BACKGROUND: Recent data suggest an early outcome benefit with reduction in
      cholesterol using statin therapy in patients with coronary artery disease (CAD).
      This may be caused by effects of low-density lipoprotein cholesterol (LDL-C)
      reduction on endothelial function and vascular reactivity in the coronary bed.
      The aim of this randomized placebo-controlled study was to examine the early
      effects of important reductions in LDL-C on myocardial perfusion and peripheral
      endothelial function. METHODS AND RESULTS: Seventy-two patients with CAD and LDL
      C between 3.0 and 5.9 mmol/L (116-228 mg/dL) were randomized to receive
      simvastatin 20 mg daily, pravastatin 40 mg daily, or placebo for 8 weeks. At
      baseline, 2 weeks, and 8 weeks, patients underwent dynamic positron emission
      tomography perfusion imaging to quantify the retention of rubidium-82 as a
      measure of myocardial flow at rest and after dipyridamole stress. Patients also
      underwent brachial artery ultrasound to measure endothelium-dependent flow
      mediated vasodilatation. At 2 and 8 weeks, the simvastatin and pravastatin groups
      showed a significant reduction (P < .001) in LDL-C compared with placebo. At 8
      weeks, simvastatin led to an improvement in flow-mediated vasodilatation compared
      with placebo (6.86% +/- 4.4% vs 3.44% +/- 4.0%, P < .05), whereas pravastatin was
      not significantly different than placebo (5.62% +/- 4.1% vs 3.44% +/- 4.0%, P =
      NS). Despite this improvement in peripheral endothelial function with
      simvastatin, there were no significant differences observed in global stress flow
      and coronary flow reserve at 8 weeks with either drug. CONCLUSIONS: Short-term
      LDL reduction with simvastatin therapy improves peripheral endothelial function
      in patients with stable CAD, although an early effect on coronary vascular
      reactivity could not be demonstrated.

PMID- 15976804
TI  - Heart rate variability biofeedback as a behavioral neurocardiac intervention to
      enhance vagal heart rate control.
AB  - BACKGROUND: Patients with coronary heart disease (CHD) who experience depressed
      mood or psychological stress exhibit decreased vagal control of heart rate (HR),
      as assessed by spectral analysis of HR variability (HRV). Myocardial infarction
      and sudden cardiac death are independently associated with depression and stress,
      as well as impaired vagal HR control. This study examined whether a behavioral
      neurocardiac intervention to reduce stress or depression can augment cardiovagal
      modulation in CHD patients. We hypothesized that (1) cognitive-behavioral
      training with HRV biofeedback would augment vagal recovery from acute stress, and
      (2) vagal regulation of HR would be inversely associated with stress and
      depression after treatment. METHODS: This randomized controlled trial enrolled 46
      CHD patients from 3 clinics of CHD risk reduction in Toronto and Vancouver,
      Canada. Subjects were randomized to five 1.5-hour sessions of HRV biofeedback or
      an active control condition. Outcome was assessed by absolute and normalized high
      frequency spectral components (0.15-0.50 Hz) of HRV, and by the Perceived Stress
      Scale and Centre for Epidemiologic Studies in Depression scale. RESULTS: Both
      groups reduced symptoms on the Perceived Stress Scale (P = .001) and Centre for
      Epidemiologic Studies in Depression scale (P = .004). Hierarchical linear
      regression determined that improved psychological adjustment was significantly
      associated with the high-frequency index of vagal HR modulation only in the HRV
      biofeedback group. Adjusted R 2 was as follows: HRV biofeedback group, 0.86 for
      stress (P = .02) and 0.81 for depression (P = .03); versus the active control
      group, 0.04 (P = .57) and 0.13 (P = .95), respectively. CONCLUSION: A novel
      behavioral neurocardiac intervention, HRV biofeedback, can augment vagal HR
      regulation while facilitating psychological adjustment to CHD.

PMID- 15976807
TI  - Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control
      of the fission yeast genome.
AB  - The organization of eukaryotic genomes into distinct structural and functional
      domains is important for the regulation and transduction of genetic information.
      Here, we investigated heterochromatin and euchromatin profiles of the entire
      fission yeast genome and explored the role of RNA interference (RNAi) in genome
      organization. Histone H3 methylated at Lys4, which defines euchromatin, was not
      only distributed across most of the chromosomal landscape but was also present at
      the centromere core, the site of kinetochore assembly. In contrast, histone H3
      methylated at Lys9 and its interacting protein Swi6/HP1, which define
      heterochromatin, coated extended domains associated with a variety of repeat
      elements and small islands corresponding to meiotic genes. Notably, RNAi
      components were distributed throughout all these heterochromatin domains, and
      their localization depended on Clr4/Suv39h histone methyltransferase. Sequencing
      of small interfering RNAs (siRNAs) associated with the RITS RNAi effector complex
      identified hot spots of siRNAs, which mapped to a diverse array of elements in
      these RNAi-heterochromatin domains. We found that Clr4/Suv39h predominantly
      silenced repeat elements whose derived transcripts, transcribed mainly by RNA
      polymerase II, serve as a source for siRNAs. Our analyses also uncover an
      important role for the RNAi machinery in maintaining genomic integrity.

PMID- 15976808
TI  - Pharmacogenomics in psychiatry: clinical issues to be considered.

PMID- 15976810
TI  - Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities.
AB  - DJ-1 is a multifunctional protein that plays roles in transcriptional regulation
      and antioxidative stress, and loss of its function is thought to result in the
      onset of Parkinson's disease (PD). Here, we report that DJ-1 was sumoylated on a
      lysine residue at amino-acid number 130 (K130) by PIASxalpha or PIASy. The K130
      mutation abrogated all of the functions of DJ-1, including ras-dependent
      transformation, cell growth promotion and anti-UV-induced apoptosis activities.
      Sumoylation of DJ-1 was increased after UV irradiation concomitant with a pI
      shift to an acidic point of DJ-1. Furthermore, L166P, a mutant DJ-1 found in PD
      patients, and K130RX, an artificial mutant containing four mutations in DJ-1,
      were improperly sumoylated, and they became insoluble, partly localized in the
      mitochondria and degraded by the proteasome system. Both L166P-expressing cells
      and DJ-1-knockdown cells were found to be highly susceptible to UV-induced cell
      apoptosis.

PMID- 15976811
TI  - Lentiginous melanoma: a histologic pattern of melanoma to be distinguished from
      lentiginous nevus.
AB  - Atypical lentiginous melanocytic proliferations in elderly patients continue to
      pose a diagnostic dilemma with lesions variably categorized as dysplastic nevus,
      atypical junctional nevus, melanoma in situ (early or evolving) and premalignant
      melanosis. We present pigmented lesions from 16 patients (seven male and nine
      female) and with the exception of one case, all were older than 50 years of age.
      The anatomical sites included trunk (7), head and neck (6) and upper extremity
      (3). The clinical diagnosis was variable and included lentigo maligna, atypical
      nevus, pigmented basal cell carcinoma, seborrheic keratosis and lentigo. The
      initial biopsies mimicked lentiginous nevus or dysplastic nevus and were
      characterized by a lentiginous proliferation of melanocytes at the dermoepidermal
      junction both as single cells and as small nests with areas of confluent growth,
      extending to the edges of the biopsy. The retiform epidermis was maintained and
      pagetoid spread of melanocytes was not prominent in hematoxylin- and eosin-
      stained sections. Dermal fibrosis was variably present and the melanocytic
      proliferation demonstrated cytological atypia. The subsequent re-excisions
      demonstrated similar atypical melanocytic proliferation occurring over a broad
      area flanking the prior biopsy sites. The diagnosis of melanoma was more easily
      recognized in the complete excision specimens. Immunohistochemical stains for
      Mitf and Mart-1 highlighted the extent of the basalar melanocytic proliferation
      as well as foci of pagetoid spread by melanocytes. Familiarity with this pattern
      of early melanoma should facilitate proper classification of lentiginous
      melanocytic proliferations in biopsies from older adults.

PMID- 15976812
TI  - Alternative epithelial markers in sarcomatoid carcinomas of the head and neck,
      lung, and bladder-p63, MOC-31, and TTF-1.
AB  - Sarcomatoid carcinomas are rare malignancies which represent poorly
      differentiated epithelial tumors that may be difficult to recognize as such.
      While some cases may have obvious epithelial areas, the sarcomatoid areas are
      poorly distinguishable from true sarcoma at the light microscopic level and, by
      immunohistochemistry, often show only limited staining for traditional epithelial
      markers such as cytokeratin or epithelial membrane antigen. This can be
      particularly problematic for diagnosis on small biopsy specimens. We sought to
      assess the diagnostic utility of several immunohistochemical markers of
      epithelial differentiation including p63, MOC-31, and thyroid transcription
      factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell
      carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were
      compared to immunohistochemistry for the traditional epithelial markers pan
      cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest
      diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and
      urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in
      many cases where immunohistochemistry was negative for both pan-cytokeratin and
      epithelial membrane antigen. All three alternative markers were quite specific
      for epithelial differentiation, each staining less than 10% of the control group
      of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell
      lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and
      epithelial membrane antigen may have diagnostic utility in this context.

PMID- 15976813
TI  - Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their
      prognostic significance in human breast cancer.
AB  - Mucins are a large family of glycoproteins expressed by many epithelial cells and
      their malignant counterparts. Much interest has been focused on expression of its
      members in breast cancer because of their potential role as prognostic indicators
      and their involvement in cancer therapy. We have examined 1447 cases of invasive
      breast carcinoma with a long-term follow-up, using tissue microarray (TMA)
      technology and immunohistochemistry to evaluate the expression profiles of
      several mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and to assess their
      prognostic value. We detected MUC1 expression in 91% of tumours. MUC1
      overexpression was associated with a lower grade, smaller tumour size, a higher
      oestrogen receptor (ER)-positive phenotype and absence of both regional
      recurrence and distance metastasis. The subcellular localization but not the
      level of expression had a prognostic value in predicting outcome. The aberrant
      cytoplasmic and membranous localization of MUC1 was associated with poor outcome
      compared with apical localization, which is the normal physiological site of
      expression. MUC2 expression was noticed in only 8.3% of all cases and was
      restricted to the cytoplasm of the tumour cells. An inverse trend was identified
      between MUC2 expression and lymph node stage and vascular invasion status. On
      excluding cases of mucinous carcinoma from the analysis, the inverse association
      with vascular invasion was still defined and in addition an inverse association
      with ER status emerged. MUC3 expression was detected in 91% of cases and its
      expression was associated with increased local recurrence, and lymph node stage.
      The membranous expression of MUC3 was found to be a potentially poor prognostic
      feature, with higher grade and poorer Nottingham Prognostic Index (NPI), and
      negative ER expression. MUC4, MUC5AC and MUC6 were expressed in 95, 37 and 20% of
      cases, respectively. Apart from an association between MUC4 expression and tumour
      grade and between MUC6 and ER-negative tumours, no other associations with any
      clinicopathological variables were found. Apart from the higher expression of
      MUC2 and MUC6 in mucinous carcinomas, no association was found between the
      expression of different mucins and tumour type. No association between the level
      of expression of any of the studied mucins and patient outcomes has been
      identified. In conclusion, most breast carcinomas express MUC1, MUC3 and MUC4.
      Among the various mucins expressed in breast cancer, MUC1 and MUC3 are potential
      prognostic indicators, MUC1 having the strongest relationship with patient
      outcome.

PMID- 15976814
TI  - DeltaNp63 expression in pancreas and pancreatic neoplasia.
AB  - DeltaNp63 (DNp63) has become widely used, in particular, for distinguishing
      invasive carcinomas from noninvasive ducts by highlighting the myoepithelial or
      basal cells in the breast and prostate, respectively. It is not known whether
      this marker may have any application in another exocrine organ, the pancreas. As
      the ductal and intraductal proliferations of this organ become better
      characterized, the need for markers to distinguish among these processes
      increases. We investigated immunohistochemical expression of DNP63 in 105 cases.
      A total of 25 cases were non-neoplastic pancreata, 25 were pancreatic
      intraepithelial neoplasia (PanIN) of various grades, and 50 were examples of
      pancreatic ductal adenocarcinoma. Sections of non-neoplastic pancreata included
      various types of non-neoplastic processes such as squamous/transitional
      metaplasia (five cases), which can be mistaken for high-grade PanINs, as well as
      various degrees of reactive ductal atypia and incidental microcysts with
      attenuated lining (five cases). No DNp63 expression was noted in normal
      pancreatic ducts. On the other hand, all five foci of squamous/transitional
      metaplasia were strongly and uniformly positive for this marker. DNp63 labeling
      was also noted in those incidental microcysts lined by attenuated cells, seen
      amidst normal pancreatic lobules. All PanINs were negative. Among invasive
      carcinomas, DNp63 expression was detected only in areas of squamous
      differentiation and was completely absent in ordinary ductal areas. Based on this
      observation, five additional cases of adenosquamous/squamous carcinoma was
      retrieved and stained, and the squamous components of all of these were also
      positive. In conclusion, (I) DNp63 is a reliable marker of squamous
      differentiation in the pancreas. It is valuable in distinguishing
      squamous/transitional metaplasia from PanINs, a distinction of importance for
      both researchers and diagnosticians. Among invasive carcinomas, it seems to be
      entirely specific for areas of squamous differentiation. (II) Those incidental
      microcysts seen in acinar lobules and lined by attenuated cells are also positive
      for DNp63, which suggests that they may be metaplastic in nature, and that they
      do not represent neoplastic cells. (III) Unlike the ducts of other exocrine
      organs, breast and prostate, there are no DNp63-expressing cells in the normal
      pancreatic ducts, and therefore, this marker cannot be used in distinguishing
      invasive carcinomas from the non-invasive ducts. (IV) No p63-expressing 'stem'
      cells are present in the pancreas.

PMID- 15976815
TI  - Monitoring the safety of licensed medicines.
AB  - The withdrawal of the selective cyclooxygenase 2 inhibitor rofecoxib owing to
      cardiovascular side effects ignited debate about the need for major changes to
      current mechanisms for post-marketing surveillance (PMS) of drug safety. Here, we
      discuss the current mechanisms, whether they are being used appropriately, and
      consider the need for changes to regulatory systems.

PMID- 15976816
TI  - Ageing and metabolism: drug discovery opportunities.
AB  - There has recently been significant progress in our understanding of the
      mechanisms that regulate ageing, and it has been shown that changes in single
      genes can dramatically extend lifespan and increase resistance to many diseases.
      Furthermore, many of these genes belong to evolutionarily conserved pathways that
      also control energy metabolism. In this review, we describe the shared molecular
      machinery that regulates ageing and energy metabolism. Although drugs to slow
      ageing face severe regulatory hurdles, it is likely that an understanding of
      ageing pathways will help to identify novel drug targets to treat metabolic
      disorders and other age-related diseases.

PMID- 15976817
TI  - Sense and sensibility in bacteria. VIIIth International Conference on Bacterial
      Locomotion and Sensory Transduction.

PMID- 15976818
TI  - New frontiers in immunology. Workshop on the road ahead: future directions in
      fundamental and clinical immunology.

PMID- 15976819
TI  - How epigenetics integrates nuclear functions. Workshop on epigenetics and
      chromatin: transcriptional regulation and beyond.

PMID- 15976820
TI  - E2F1 is crucial for E2F-dependent apoptosis.
AB  - Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results
      have suggested that this is dependent on the E2F transcription factors. However,
      so far, the ability of the different E2F family members to contribute to
      apoptosis is controversial. Here, we show that ectopic expression of E2F3 results
      in apoptosis in both primary mouse fibroblasts and transgenic mice. Apoptosis
      induced by E2F3 is associated with the accumulation of E2F1 and, strikingly, we
      found that E2F3-induced apoptosis is dependent on E2F1. On the basis of these
      results, we propose that the accumulation of crucial levels of E2F1 activity, and
      not total E2F activity, is essential for the induction of apoptosis in response
      to a deregulated pRB pathway. These results are consistent with previous findings
      that E2F1, but not other E2Fs, can have tumour-suppressing activities.

PMID- 15976822
TI  - [Not for sissies].

PMID- 15976821
TI  - Cross-talk between the mechano-gated K2P channel TREK-1 and the actin
      cytoskeleton.
AB  - TREK-1 (KCNK2) is a K(2P) channel that is highly expressed in fetal neurons. This
      K(+) channel is opened by a variety of stimuli, including membrane stretch and
      cellular lipids. Here, we show that the expression of TREK-1 markedly alters the
      cytoskeletal network and induces the formation of actin- and ezrin-rich membrane
      protrusions. The genetic inactivation of TREK-1 significantly alters the growth
      cone morphology of cultured embryonic striatal neurons. Cytoskeleton remodelling
      is crucially dependent on the protein kinase A phosphorylation site S333 and the
      interactive proton sensor E306, but is independent of channel permeation.
      Conversely, the actin cytoskeleton tonically represses TREK-1 mechano
      sensitivity. Thus, the dialogue between TREK-1 and the actin cytoskeleton might
      influence both synaptogenesis and neuronal electrogenesis.

PMID- 15976823
TI  - [How to medicate for the brain?].

PMID- 15976824
TI  - [Detection of chlamydia trachomatis in urine, vulval and cervical swabs].
AB  - BACKGROUND: Increased testing rates for Chlamydia infection among young women can
      be achieved by more use of self-administered sampling methods. In this study,
      vulval swabs and urine are compared to conventional cervix samples. MATERIALS AND
      METHODS: Vulval swabs, urine and cervix samples from 541 young, healthy women
      were tested for Chlamydia by polymerase chain reaction technique. RESULTS: The
      prevalence of Chlamydia infection was 4.1% (22/541). The sensitivity (cervix
      22/22, urine 21/22 and vulva 21/22) and specificity (no false negative results)
      were high for all sampling sites. INTERPRETATION: Urine samples or vulval swabs
      can replace conventional cervix swabs for the detection of Chlamydia.

PMID- 15976825
TI  - [Testing pattern and prevalence of Chlamydia infection among women].
AB  - BACKGROUND: Chlamydia notification rates have increased in Norway over the recent
      years. The increase in notification cannot be interpreted as an increase in
      chlamydia prevalence since knowledge of testing patterns and prevalence of
      chlamydia by sex and age is virtually absent. MATERIAL AND METHODS: A data set,
      applying the woman as unit for analyses, comprising all test activity in one
      Norwegian county, was created for the period 1990-2003 (women 15-59 years old,
      resident in Sor-Trondelag County, n = 56,220). Tests registered within 60 days
      from the previous test were excluded. Outcome measures are age-specific testing
      rates (first test), cumulative incidence of first test and incidence of repeated
      testing, proportion of positive first tests and cumulative incidence of being
      diagnosed with chlamydia before the age of 25, and 12-month incidence of
      chlamydia. RESULTS: Testing rates were high among young women throughout the
      study period. By the age of 25, almost all women had been tested at least once
      for chlamydia (85-90%). By the end of the year following the first test, one in
      five women with a negative first test and one in three women with a positive
      first test had been tested for chlamydia at least once more. The proportion of
      positive tests was highest among the youngest women (9-11% for women 15-24 years
      from 2000). Cumulative incidence of diagnosed chlamydia by the age of 25 years
      was 15% for women born 1976-79. Incidence of chlamydia during the first year
      after the first test was 2-3%. The relative risk for being diagnosed with
      chlamydia after the first test was highest for women who initially tested
      positive, and for teenagers. INTERPRETATION: The prevalence of chlamydia is high
      among young women. However, many women are not tested within a reasonable time
      after their first intercourse. Increased testing rates among teenagers can be
      achieved by focusing on easily available tests implying self-sampling methods.

PMID- 15976826
TI  - [Testing pattern and prevalence of Chlamydia infections among men].
AB  - BACKGROUND: The knowledge of testing patterns and prevalence of chlamydia among
      Norwegian men is sparse. MATERIALS AND METHODS: Data on chlamydia tests for men
      were selected from the database at the only laboratory in a Norwegian county
      carrying out chlamydia tests. 12,633 men aged 15-59 at first test and resident in
      the county were included in the study. RESULTS: Age-specific rates for first test
      for young men increased throughout the study period. By the age of 25, one in
      five men had been tested for chlamydia at least once. One in six of first tests
      was positive. Chlamydia prevalence at first test was highest among men 20-24
      years old (21% in 2003). Men who initially had a positive test more often had a
      repeated test than men who initially had a negative test. Furthermore, 12-month
      incidence of chlamydia infection subsequent to the first test was higher among
      men who initially tested positive (12%) than among men who initially tested
      negative (7%). INTERPRETATION: Even though testing rates increased throughout the
      study period, the proportion of men who had been tested for chlamydia at the age
      of 25 was low. The prevalence at first test was high throughout the study period.
      Increased availability of urine-based testing will probably lead to more
      chlamydia testing among men.

PMID- 15976827
TI  - [Prevalence of genital Chlamydia trachomatis infection in the age group 18-29
      years in Oslo].
AB  - BACKGROUND: Earlier Norwegian prevalence studies of genital C. trachomatis
      infection have mainly been carried out among women and in selected patient
      groups. We decided to do a population-based prevalence study among young men and
      women in Oslo. The study was done within the framework of the new Norwegian list
      patient system, in which each citizen is assigned to one particular doctor.
      METHODS: Cross-sectional study. All patients 18-29 years old listed with a group
      practice in Oslo received a personal letter of invitation. We asked each person
      to submit a urine sample and fill in a questionnaire. The urinary samples were
      tested by means of a DNA amplification method. Non-respondents received one
      reminder. RESULTS: 685 persons were invited to participate, 234 responded (36%);
      169 females (43%) and 65 males (25%). A total of 6 respondents (3%, 95% CI 1.2
      5.5) tested positively, 4 of them were males. At least 51% of the females and 25%
      of the males had previously been examined for C. trachomatis, and at least 18% of
      the females and 8% of the males had received treatment. A total of 70% stated
      that they would see their doctor if they suspected a genital chlamydial
      infection. INTERPRETATION: Opportunistic testing for C. trachomatis infection
      should be offered more frequently to young men. A national prevalence study of
      genital chlamydial infection should be carried out. The new list patient system
      offers new opportunities for research in primary medical care in Norway.

PMID- 15976828
TI  - [Typhoid and paratyphoid fever in children].
AB  - BACKGROUND: Febrile illness without focal symptoms in a child who has visited
      tropical or sub-tropical areas is an increasing health problem in western
      countries. In the department of paediatrics at Ullevaal University Hospital,
      malaria, typhoid and paratyphoid fever are the most frequent infectious diseases
      acquired in tropical or sub-tropical areas. MATERIALS AND METHODS: We describe
      all 31 children under 16 admitted between 1998 and 2003 who had blood cultures
      positive for Salmonella typhi or Salmonella paratyphi A or B. RESULTS: Nearly all
      the children were second or third generation immigrants from the Indian
      subcontinent. Fever was the main symptom at onset. Out of 31 salmonella strains,
      8 showed reduced sensitivity to quinolones, which are the drugs of choice.
      Clinical poor response to treatment is associated with reduced sensitivity to
      nalidixic acid in vitro. CONCLUSION: Blood cultures prior to administration of
      antibiotics are important in providing correct diagnosis and appropriate
      treatment. Before visiting endemic areas, groups at risk should be informed that
      there are vaccines available against typhoid fever.

PMID- 15976829
TI  - [Medical prophylaxis and treatment of steroid induced osteoporosis].
AB  - BACKGROUND: Glucocorticoid steroids are widely used as antiinflammatory and
      immunosuppressive medications and are well known to induce osteoporosis. MATERIAL
      AND METHODS: Randomised clinical trials and Cochrane reports on the use of
      calcium, vitamin D, bisphosphonates and hormones were reviewed and the results
      summarised. Additionally, national and some international recommendations were
      reviewed in order to propose recommendations for prophylaxis and treatment. The
      literature was identified by Medline searches. RESULTS AND INTERPRETATION:
      Calcium and vitamin D prevent bone loss in low-to-medium-dose glucocorticoid
      steroid therapy. Bisphosphonates maintain or modestly increase lumbar and hip
      bone mass. The fracture risk was not significantly reduced in the spine and the
      hip. The clinical randomised trials and Cochrane reports conclude that
      bisphosphonates as well as calcium and vitamin D taken together are effective and
      the drugs of choice in prevention and treatment.

PMID- 15976830
TI  - [Diabetic neuropathy--a clinical review].
AB  - BACKGROUND: Diabetic neuropathy is an often overlooked common complication of
      diabetes. METHODS: This review is based on papers identified on Medline and our
      own clinical experience. RESULTS AND INTERPRETATION: Diabetic neuropathies can be
      classified as reversible or chronic. The most common type is the chronic,
      progressive distal symmetric polyneuropathy where sensory symptoms in the lower
      limbs dominate. These patients often lose their protective sensibility and are at
      risk of foot ulcers and amputations; distressing pain is another symptom of this
      disorder. Autonomic neuropathy is often a feature of progressive polyneuropathy,
      but is rarely symptomatic. Mononeuropathies affecting femoral, truncal or ocular
      nerves are among the reversible neuropathies of diabetes. Distal symmetric
      diabetic neuropathy is very common; overall prevalence among diabetic patients is
      around 20-30%. The prevalence increases with the duration of the disease as well
      as with poor glycaemic control, height and age. The pathogenesis of diabetic
      neuropathies is not clear, but possibly involves a complex of metabolic factors
      inducing nerve ischaemia. We recommend yearly screening for most diabetic
      patients with a simple screening instrument consisting of four questions and four
      simple tests. Tight glycaemic control has been shown to protect against or delay
      the occurrence of neuropathy. Tricyclic antidepressants are still the drugs of
      choice against painful diabetic neuropathy, but gabapentin and tramadol are new
      alternatives.

PMID- 15976831
TI  - [Mycophenolate mofetil--a new therapeutic agent for chronic autoimmune diseases].
AB  - BACKGROUND: Mycophenolate mofetil is an immunosuppressive agent frequently used
      in regimens to prevent allograft rejection. In this review we focus on
      mycophenolate mofetil as a potential drug for chronic autoimmune diseases.
      MATERIALS AND METHODS: We searched PubMed for relevant literature and present two
      case histories. RESULTS AND INTERPRETATION: Treatment with mycophenolate mofetil
      is best documented in lupus nephritis. In this context, some studies have
      documented an effect equal to cyclophosphamide for induction treatment, and equal
      to azathioprine, and better than cyclophosphamide for remission maintenance.
      Mycophenolate mofetil is today an alternative, although experimental, agent for
      the treatment of certain autoimmune diseases when conventional drugs have failed
      or are not tolerated; in the future it may become more widely used for
      immunosuppression. To establish the role for mycophenolate mofetil, more
      prospective controlled multicentre studies are warranted.

PMID- 15976832
TI  - [Actinic keratosis and development of cutaneous squamous cell carcinoma].
AB  - BACKGROUND: Actinic keratosis is a common sun-induced skin disease. For many
      years there has been a great deal of discussion of the term used for the disease
      and of its classification. Recent molecular studies indicate an association
      between actinic keratosis and squamous cell carcinoma. MATERIAL AND METHODS:
      Review of recent reports on histological, molecular, biochemical and clinical
      findings in actinic keratosis and cutaneous squamous cell carcinoma. RESULTS AND
      INTERPRETATION: The morphology of atypical cells in both actinic keratosis and
      squamous cell carcinoma is identical. The risk of progression to squamous cell
      carcinoma is minimal, but up to 60% of squamous cell carcinoma cases begin as
      actinic keratosis. Regression of actinic keratosis occurs when sun exposure is
      decreased. Examination of possible chromosome aberrations and gene mutations in
      both actinic keratosis and squamous cell carcinoma reveals similar patterns,
      including the same mutation in the tumour suppressor gene TP53. Recent studies
      indicate that actinic keratosis is the earliest manifestation of a potentially
      malignant disease similar to carcinoma in situ in cervix uteri. Thus, actinic
      keratosis requires careful diagnosis and follow up.

PMID- 15976833
TI  - [Stroke: when the diagnosis is wrong].
AB  - BACKGROUND: There is a lack of knowledge of stroke symptoms in the population and
      among health professionals. Many non-cerebrovascular diseases present with a
      strokelike clinical picture. The present study focuses on non-cerebrovascular
      conditions that were referred to a neurological acute stroke unit as strokes.
      METHODS: In an observational study, 354 consecutive patients who presented to the
      stroke unit with a diagnosis of stroke were evaluated. Patients were assessed by
      neurologists and classified as non-stroke patients or true stroke patients.
      RESULTS: Eighty-eight were non-stroke patients (25%), who were younger than the
      true strokes (65.5 vs 71.5). Clinical features were falls (23%), sensory
      impairment (19%), vertigo (13%), loss of consciousness (11%) and confusion (9%).
      Half of the non-stroke diagnoses were either migraine, infection, postural
      vertigo or sequelae after a previous stroke. In 25% another neurological disease
      was present, such as epilepsy, cranial nerve disorder, neuropathy, transient
      global amnesia or demyelinating disease. There were 6 patients with previous
      stroke among the 11 non-stroke patients who had a final diagnosis of infection.
      DISCUSSION: Misdiagnosis of stroke is common among non-neurologists. Non-stroke
      patients often have another neurological disease. All stroke patients should be
      seen by a neurologist in the early phase.

PMID- 15976834
TI  - [Radical therapy for prostate cancer in Norway].
AB  - There is an increasing incidence of localised prostate cancer in Norway.
      Treatment decisions should be based on published results for treatment
      modalities. This paper presents an overview of Norwegian results published
      between 1982 and 2003. The treatment modalities used were: transurethral
      resection of the prostate followed by laser coagulation, radical prostatectomy,
      external beam radiation, cryotherapy, and brachytherapy. There were no controlled
      studies and no evidence that the treatment offers health benefit to the patients.
      The observation periods were generally very short. Frequency of complications is
      significant. Radical surgery is followed by 8-77% urinary incontinence, 38-96%
      loss of erection, and 25% other complications. External beam radiation gives 20%
      lower urinary tract symptoms, 51% loss of erection and 13-86% intestinal
      complications. For cryotherapy there is no incontinence, 74% erectile failures
      and 10-43% other complications.

PMID- 15976835
TI  - [Cryotherapy for prostate cancer].
AB  - BACKGROUND: The paper describes the principles and technique of cryotherapy for
      prostate cancer. MATERIAL AND METHODS: From September 2003 to January 2005 we
      have treated 40 patients with localised prostate cancer. Among patients with T1-2
      tumours, Gleason score < 7 and PSA < 10 ng/ml, average prostate-specific antigen
      (PSA) after 3 months is 0.32 (< 0.05-1.2) ng/ml. Among patients with T1-2,
      Gleason score > or = 7 or PSA > or = 10, average PSA after 3 months is 0.56 (<
      0.05-1.9) ng/ml. RESULTS AND DISCUSSION: Two patients needed intermittent
      catheterisation for a short period and underwent revision of the prostatic
      cavity. After 3 months, however, all patients had normal micturition. The
      prostate was not palpable in any of the patients. Our experience is encouraging
      and comparable to what has recently been reported from other countries.

PMID- 15976837
TI  - [Glucosamine for relief of symptoms in osteoarthritis].

PMID- 15976836
TI  - [Clinical experience with TNF-alpha inhibitors in rheumatoid arthritis].
AB  - BACKGROUND: Infliximab and etanercept, both tumour necrosis factor-alpha
      inhibitors, are proven to be effective in patients with rheumatoid arthritis in
      randomised controlled trials. MATERIAL AND METHODS: Patients with active
      rheumatoid arthritis were treated with infliximab (n = 29) or etanercept (n = 24)
      in clinical hospital practice. They were examined before and during treatment.
      All patients had tried at least one DMARD before. Details of disease activity
      were monitored by measuring tender and swollen joints, global and pain patient
      visual analogue scales, Disease Activity Index Score (DAS 28), the Modified
      Health Assessment Questionnaire, blood and urine samples, and adverse effects.
      The patients were monitored regularly for two years or until they stopped
      treatment. RESULTS: In the infliximab group we observed statistically
      significantly better values for all the registered variables after 6 weeks. At
      the other times of registration the variables were varying a lot; however, DAS 28
      scores after baseline were all within the limits of moderate effect. In the
      etanercept group we observed statistically significantly better values for all
      the variables except for erythrocyte sedimentation rate after 6 weeks. At the
      other times of registration all the variables had significantly better values.
      Adverse effects were reported in 9 patients in the infliximab group and in 5 in
      the etanercept group, but no serious adverse effects were reported. 18 patients
      in the infliximab group (61%) and 10 in the etanercept group (42%) had stopped
      treatment within two years, either because of adverse effects or lack of effect.
      CONCLUSION: In this open study of patients with active rheumatoid arthritis, most
      experienced a rapid effect of infliximab, but a varying effect later on. In the
      etanercept group the patients experienced both a rapid and sustained effect among
      those who tolerated the medication. Compared to what several others have
      reported, a large number of patients stopped treatment; this may reflect limited
      experience.

PMID- 15976838
TI  - [Diagnosis and treatment of patients with parkinsonism in nursing homes: how to
      improve quality?].
AB  - BACKGROUND: Studies have shown that diagnosing and treating patients with
      parkinsonism in nursing homes could be improved. Parkinson's disease is the most
      important cause of parkinsonism. MATERIALS AND METHODS: The data for this article
      have been obtained through a literature search and by research in our own centre.
      RESULTS AND INTERPRETATION: Parkinsonism is a frequent cause of functional
      impairment among the elderly. The diagnosis is based on an evaluation of the four
      cardinal signs of parkinsonism (resting tremor, akinesia, rigidity, and postural
      abnormalities). Parkinsonism may be caused by Parkinson's disease, symptomatic
      parkinsonism, pseudoparkinsonism or be a part of the presentation of other
      neurodegenerative diseases. A systematic examination for suspected parkinsonism
      followed by an evaluation of causes of parkinsonism will improve the diagnostic
      quality in nursing homes. Patients with Parkinson's disease have motor as well as
      non-motor problems, hence management should focus on all aspects of the symptoms
      experienced by these patients, not only the motor symptoms. Several
      investigations have shown that non-motor problems may detract more from the
      quality of life than the motor symptoms. 5% of all residents in nursing homes in
      Norway have Parkinson's disease; 20% of them are unrecognised by the medical
      staff. Intervention in nursing homes from physicians with more knowledge on
      parkinsonism has been shown to improve diagnostic accuracy as well as management.

PMID- 15976839
TI  - [Antipsychotics against anxiety in dementia: medical treatment or chemical
      restraints?].
AB  - BACKGROUND: Antipsychotic drugs are widely used for behavioural and psychological
      symptoms of dementia. We discuss the evidence for this treatment and implications
      for clinical practice. METHOD: Literature search on Medline was supplemented by
      clinical guidelines and drug reports. RESULTS AND INTERPRETATION: Treatment with
      antipsychotic drugs for behavioural symptoms has limited effectiveness; the
      documentation is generally weaker for older than for newer drugs. Conventional
      antipsychotics give important risks of adverse events, while the newer
      antipsychotics imply increased risk of cerebrovascular events; hence, monitoring
      of effect and adverse events is imperative. Standardised methods for assessing
      behavioural symptoms, e.g. the Neuropsychiatric Inventory, are suitable for
      follow up. Controlled trials indicate that withdrawal is a feasible method for
      assessing actual drug effect and the need for continued treatment. Withdrawal
      attempts should therefore be conducted regularly for all patients taking
      antipsychotics for behavioural and psychological symptoms of dementia.

PMID- 15976840
TI  - [Sleep disturbances among nursing home patients--practical advice on treatment].
AB  - BACKGROUND: Sleep disturbances are common among nursing home patients and get
      worse with age and their degree of dementia. MATERIAL AND METHODS: The article is
      based on our own research as well as on studies and reviews in the field. RESULTS
      AND INTERPRETATION: Sleep disturbances among patients with dementia may have a
      range of internal or external causes. A thorough assessment of the patient's
      sleep pattern is crucial before treatment is instigated. Pharmacological
      interventions may have serious side effects in this population; non
      pharmacological interventions have, on the other hand, shown promise.

PMID- 15976841
TI  - [Bright light treatment against sleep disturbances in nursing homes--a non
      pharmacological alternative].
AB  - BACKGROUND: Age-related sleep disturbances may be caused by changes in the
      circadian rhythm, either by phase shifting and/or by a reduction of its
      amplitude. This may result in less nocturnal sleep and less wakefulness during
      the day. MATERIAL AND METHODS: The article is based on our own research and on
      relevant studies and reviews in this field. RESULTS AND INTERPRETATION: Bright
      light treatment may alter the phase and strengthen the existing circadian rhythm
      in patients with insomnia, thus creating a clearer distinction between night and
      day. It is reported that bright light treatment in the morning for patients with
      dementia may improve sleep maintenance.

PMID- 15976842
TI  - [Patients' experiences with and attitudes to generic substitution].
AB  - INTRODUCTION: The aim of this study was to assess patient experiences with and
      attitudes to generic substitution. MATERIAL AND METHODS: Patients who had
      purchased three to seven, or eight or more, different prescription medicines
      during the last six months were compared. Both groups were mailed a questionnaire
      about generic substitution. RESULTS: The response rate was 73% (281/386), the
      average age of respondents was 66. There was a correlation between patients
      remembering that information had been provided by their physicians and subsequent
      generic substitution. Out of 138 patients who had experienced generic
      substitution, 50 patients (36%) reported one or more negative experiences, 21% an
      altogether negative experience. About 41% of the patients would not switch given
      no personal economic insertives. There were no significant correlations between
      experiences with generic substitution and age, gender, number of different drugs
      used, information provided by the physician or by the pharmacy staff.
      INTERPRETATION: About 78% of the patients are satisfied with generic substitution
      although 1/3 report one or more negative experiences. In order to raise patient
      satisfaction, there is a need for increased economic incentives and a strategy
      whereby physicians, pharmacies and official authorities cooperate on information
      to the public.

PMID- 15976843
TI  - [Is there a relationship between hospital size and patient experience?].
AB  - BACKGROUND: Hospitals in Norway are undergoing changes in structure and
      organisation. Patient experience has been selected as a national indicator of
      hospital quality. The objective of this study was to investigate the relationship
      between hospital size and patient experience. MATERIAL AND METHODS: A patient
      experience questionnaire was sent to a representative sample of patients after
      discharge from 46 somatic hospitals, which were classified by function and by
      annual number of patients admitted. RESULTS: 10,975 patients (50%) responded.
      Generally, the patients expressed a positive attitude towards their hospitals.
      The patient experience was significantly more positive among those discharged
      from small hospitals than among those discharged from medium-sized or large
      hospitals, especially with regard to organisation. INTERPRETATION: Our study
      shows that patient experience was significantly more positive among those
      discharged from small hospitals than from medium-sized or large hospitals,
      especially with regard to organisation. However, the score differences between
      hospitals are small and should be interpreted with caution.

PMID- 15976844
TI  - [Micturating cystourethrography--are the practical routines in accordance with
      empirical knowledge?].
AB  - BACKGROUND: Micturating cystourethrography (MCUG) is a radiological examination
      of the urethra, bladder and kidneys frequently performed in children. The
      examination is known to be distressing for the child as well as parents and
      staff. The literature shows that proper information to both children and parents
      and the use of distraction techniques during the MCUG can lessen the children's
      distress and increase their cooperation. The use of sedation makes MCUG less
      distressing for the child, with very few side effects and no negative effects on
      the outcome of the examination. The aim was to study how Norwegian university
      hospitals apply empirical knowledge in their MCUG routines. MATERIAL AND METHODS:
      The study is based on observations of MCUG examinations of six children, mean age
      3 years (range 6 months to 8 years). A questionnaire on MCUG routines and use of
      written information was completed by six departments of radiology. RESULTS: All
      the hospitals sent written information, though of varying quality and only in
      Norwegian, to patients/parents before the MCUG. The hospitals reported the use of
      different types of distraction techniques. Sedation with midazolam was used in
      all the hospitals, but the frequency varied from 6% to 75% of the examined
      children. CONCLUSION: The MCUG routines in Norwegian university hospitals are to
      varying extent in accordance with empirical recommendations; there is still scope
      for improvements with regard to written and oral information, distraction
      techniques and sedation.

PMID- 15976846
TI  - [Communicable disease control and international politics].

PMID- 15976848
TI  - [A deep-drawn sigh from a clinician].

PMID- 15976850
TI  - [Reliability and HIV/AIDS].

PMID- 15976851
TI  - New directions in supramolecular transition metal catalysis.
AB  - Supramolecular chemistry has grown into a major scientific field over the last
      thirty years and has fueled numerous developments at the interfaces with biology
      and physics, clearly demonstrating its potential at a multidisciplinary level.
      Simultaneously, organometallic chemistry and transition metal catalysis have
      matured in an incredible manner, broadening the pallet of tools available for
      chemical conversions. The interface between supramolecular chemistry and
      transition metal catalysis has received surprisingly little attention. It
      provides, however, novel and elegant strategies that could lead to new tools in
      the search for effective catalysts, as well as the possibility of novel
      conversions induced by metal centres that are in unusual environments. This
      perspective describes new approaches to transition metal catalyst development
      that evolve from a combination of supramolecular strategies and rational ligand
      design, which may offer transition metal catalysts for future applications.

PMID- 15976852
TI  - Near IR emitting isothiocyanato-substituted fluorophores: their synthesis and
      bioconjugation to monoclonal antibodies.
AB  - Two near IR emitting fluorophores, based on the phthalocyanine and
      naphthalocyanine chromophores, which also bear a single isothiocyanato group
      suitable for conjugation to proteins are reported; their utility as luminescent
      probes is demonstrated by conjugation to monoclonal antibodies and the ability of
      these conjugates to selectively bind cells bearing the relevant antigen.

PMID- 15976853
TI  - Oxidation of N-substituted dopamine derivatives: irreversible formation of a
      spirocyclic product.
AB  - Oxidation of amide, urea and guanidinium derivatives of dopamine gives relatively
      stable ortho-quinones whereas oxidation of corresponding thioamide and amidinium
      derivatives rapidly and quantitatively gives novel bicyclic and spirocyclic
      products formed via the corresponding ortho-quinone.

PMID- 15976854
TI  - Enhancing selectivity in oxidation catalysis with sol-gel nanocomposites.
AB  - Valuable organic compounds such as alpha-hydroxy acids are easily synthesised
      with relevant selectivity enhancement using a sol-gel hydrophobized
      nanostructured silica matrix doped with the organocatalyst TEMPO: A materials
      science based synthetic route which cannot be achieved via classical homogeneous
      synthesis.

PMID- 15976855
TI  - Divalent ligand for intramolecular complex formation to streptavidin.
AB  - Monovalent ligand and divalent ligand have been synthesized, and their
      thermodynamic parameters of complexation to avidin and streptavidin have been
      analyzed in terms of multivalent binding.

PMID- 15976856
TI  - New odourless protocols for efficient Pauson-Khand annulations.
AB  - An inexpensive and commercially available odourless additive, dodecyl methyl
      sulfide, has been shown to be a highly effective promoter in the Pauson-Khand
      cyclisation of both intra- and intermolecular substrates, affording good to
      excellent yields of cyclopentenone products.

PMID- 15976857
TI  - The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: the AB
      spiroacetal segment.
AB  - The convergent synthesis of the C1-C15 AB-spiroacetal subunit of altohyrtin
      A/spongistatin 1 is described. This highly stereocontrolled synthesis relies on
      matched boron aldol reactions of chiral methyl ketones, under Ipc(2)BCl
      mediation, to establish the C5, C9 and C11 stereocentres, and formation of the
      desired thermodynamic spiroacetal under acidic conditions. The scalable synthetic
      sequence developed provided access to multi-gram quantities of , thus enabling
      the successful completion of the total synthesis of altohyrtin A/spongistatin 1,
      as reported in Part 4.

PMID- 15976858
TI  - The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: the CD
      spiroacetal segment.
AB  - Stereocontrolled syntheses of the C16-C28 CD-spiroacetal subunit of altohyrtin
      A/spongistatin 1 , relying on kinetic and thermodynamic control of the
      spiroacetal formation, are described. The kinetic control approach resulted in a
      slight preference (60 : 40) for the desired spiroacetal isomer. The thermodynamic
      approach allowed ready access to the desired spiroacetal by acid-promoted
      equilibration, chromatographic separation of the C23 epimers and resubjection of
      the undesired isomer to the equilibration conditions. This scalable synthetic
      sequence provided multi-gram quantities of , thus enabling the successful
      completion of the total synthesis of altohyrtin A/spongistatin 1, as reported in
      Part 4 of this series.

PMID- 15976859
TI  - The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: the southern
      hemisphere EF segment.
AB  - The fully functionalised C29-C51 southern hemisphere of altohyrtin A/spongistatin
      1 , incorporating the E- and F-ring tetrahydropyran rings and the unsaturated
      side chain, has been synthesised in a highly convergent and stereocontrolled
      manner. Key steps in the synthesis of this phosphonium salt include four highly
      diastereoselective, substrate-controlled, boron aldol reactions to establish key
      C-C bonds and accompanying stereocentres, where the introduction of the
      chlorodiene side chain and the C47 hydroxyl-bearing centre were realised by
      exploiting remote stereoinduction from the F-ring tetrahydropyran.

PMID- 15976860
TI  - The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: fragment
      couplings, completion of the synthesis, analogue generation and biological
      evaluation.
AB  - The antimitotic marine macrolide altohyrtin A/spongistatin 1 has been synthesised
      in a highly convergent and stereocontrolled manner, thus contributing to the
      replenishment of the largely exhausted material from the initial isolation work.
      Coupling of the AB- and CD-spiroacetal subunits by a stereoselective aldol
      reaction was achieved by using either a lithium (67 : 33 dr) or boron enolate (90
      : 10 dr). A highly (Z)-selective Wittig coupling was used to unite the northern
      hemisphere aldehyde with the southern hemisphere phosphonium salt . Deprotection
      and subsequent regioselective macrolactonisation on a triol seco-acid completed
      the synthesis of altohyrtin A. Two structural analogues were also prepared and
      evaluated as growth inhibitory agents against a range of human tumour cell lines,
      including Taxol-resistant strains, alongside altohyrtin A and paclitaxel (Taxol),
      revealing that dehydration in the E-ring is tolerated and results in enhanced
      cytotoxicity (at the low picomolar level), whereas the presence of the full C44
      C51 side-chain appears to be crucial for biological activity.

PMID- 15976861
TI  - Substituent effects on the stability of extended benzylic carbocations: a
      computational study of conjugation.
AB  - A set of design rules for the prediction of relative stabilities of methoxy
      substituted naphthyl methyl carbocations are presented based on a series of DFT
      calculations. The peri-effect, over-crowding, substitutions on the ring carrying
      the CH(2)(+) group and substitution on the opposite ring are the principal
      factors that influence the stability of the carbocations. All of these factors
      have to be taken simultaneously into account. The most pronounced destabilization
      occurs when the methyl part of the methoxy substituent lies out of the plane of
      the aromatic core because this causes the resonance stabilization of the
      carbocation to become hindered. The performance of the DFT-calculations was
      assessed on the results of a G3(MP2)//B3LYP calculation-a method that is known to
      predict energies to within chemical accuracy. These values were found to compare
      well with those obtained at the B3LYP/6-31G(d) level. Thus, a computationally
      inexpensive method such as the B3LYP/6-31G(d) might prove to be a powerful tool
      in the design of future complex extended aromatic systems.

PMID- 15976862
TI  - Enhanced delivery of gamma-secretase inhibitor DAPT into the brain via an
      ascorbic acid mediated strategy.
AB  - Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of
      the amyloid precursor protein (APP) to produce pathogenic Abeta peptides, is an
      attractive approach for the treatment of Alzheimer's disease. We designed a gamma
      secretase inhibitor bearing an ascorbic acid moiety which allows a specific
      delivery of the drug to the brain. Through, on the one hand, Abeta peptide
      production measurements by specific in vitro assays (gamma-secretase cell free
      assay and cell based assay on HEK 293 APP transfected cells) and on the other
      hand through pharmacokinetic studies on animal models, the new inhibitor shows a
      good pharmacokinetic profile as well as a potent gamma-secretase inhibitory
      activity in vitro. From the obtained results, it is expected that drug will be
      mainly delivered to the CNS with a low diffusion in the peripheral tissues.
      Consequently the side effects of this gamma-secretase inhibitor on the immune
      cells could be reduced.

PMID- 15976863
TI  - Spin trapping of superoxide by diester-nitrones.
AB  - The nitrone N-[(1-oxidopyridin-1-ium-4-yl)-methylidene]-1,1
      bis(ethoxycarbonyl)ethylamine N-oxide (DEEPyON) was synthesized and used as a
      spin trapping agent. The kinetic aspects of the superoxide detection by this new
      spin trap and by two other diester-nitrones, i.e. 2,2-diethoxycarbonyl-3,4
      dihydro-2H-pyrrole-1-oxide (DEPO) and N-benzylidene-1,1
      bis(ethoxycarbonyl)ethylamine N-oxide (DEEPN), were examined by determining the
      rate constants for the trapping reaction and for the spin adduct decay at pH 7.2.
      Comparing the results obtained to those given by analogous monoester-nitrones
      showed that both the spin trapping and the adduct decay reactions were faster in
      the presence of a second ester group in the cyclic nitrone series, while the
      superoxide trapping capacities of linear diester-nitrones were found to be
      dramatically weak. It follows from this study that DEPO and 2-ethoxycarbonyl-2
      methyl-3,4-dihydro-2H-pyrrole-1-oxide (EMPO) are superior when it comes to
      superoxide detection. Below 0.005 mol dm(-3), DEPO is to date the only nitrone
      capable of clearly detecting superoxide, while EMPO should be preferred at higher
      spin trap concentration.

PMID- 15976864
TI  - Expansion of repertoire of modified DNAs prepared by PCR using KOD Dash DNA
      polymerase.
AB  - Thymidine analogues bearing a variety of functional groups at the C5-position via
      an amino-linker arm were prepared and the substrate activity for PCR using
      thermophilic KOD Dash DNA polymerase was examined. The enzyme accepted the
      thymidine analogues bearing pyridine, imidazole, biotin, a cationic-charged
      guanidinium, a cationic-charged amino, mercaptopyridyl and phenanthrolne groups
      at the C5-position, forming the corresponding PCR product. However, a thymidine
      analogue bearing a carboxyl group at the C5-position was a poor substrate and the
      corresponding PCR products could not be obtained. The thymidine analogue bearing
      a mercapto group was also a poor substrate for the enzyme, because it dimerized
      by disulfide linkage under PCR conditions. The enzyme hardly accepts the
      thymidine analogues with a negatively-charged carboxyl group or a bulky group as
      a substrate. KOD Dash DNA polymerase, having a broader substrate specificity than
      any other DNA polymerase, will expand the variety of modified DNAs that can be
      prepared by PCR.

PMID- 15976865
TI  - Iodo- and bromo-enolcyclization of 2-(2-propenyl)cyclohexanediones and 2-(2
      propenyl)cyclohexenone derivatives using iodine in methanol and pyridinium
      hydrobromide perbromide in dichloromethane.
AB  - alpha-Allylcyclohexane-1,3-diones undergo one-pot iodine-methanol promoted
      iodocyclization and oxidative aromatization to afford variously substituted 2
      iodomethyltetrahydrobenzofuran-4-ones (minor) and 2-iodomethyl-4
      methoxydihydrobenzofuran derivatives (major). On the other hand, the alpha-allyl
      1,3-cyclohexanediones react with pyridinium hydrobromide perbromide in
      dichloromethane to afford mixtures of 2-bromomethyltetrahydrobenzofuran-4-ones
      (major) and 3-bromomethyltetrahydrobenzopyran-5-ones (minor). The prepared
      products and their derivatives were characterized using a combination of NMR, FT
      IR and mass spectroscopic techniques.

PMID- 15976866
TI  - Internally stabilized selenocysteine derivatives: syntheses, 77Se NMR and
      biomimetic studies.
AB  - Selenocystine ([Sec]2) and aryl-substituted selenocysteine (Sec) derivatives are
      synthesized, starting from commercially available amino acid l-serine. These
      compounds are characterized by a number of analytical techniques such as NMR (1H,
      13C and 77Se) and TOF mass spectroscopy. This study reveals that the introduction
      of amino/imino substituents capable of interacting with selenium may stabilize
      the Sec derivatives. This study further suggests that the oxidation-elimination
      reactions in Sec derivatives could be used for the generation of biologically
      active selenols having internally stabilizing substituents.

PMID- 15976867
TI  - The promise of primary health care.

PMID- 15976868
TI  - Health care has to move into the hi-tech age.

PMID- 15976869
TI  - Priority medicines and the world.

PMID- 15976870
TI  - Governments in a dilemma over bird flu.

PMID- 15976871
TI  - How bad is the environment for our health?

PMID- 15976873
TI  - Evaluating the impact of the HIV pandemic on measles control and elimination.
AB  - OBJECTIVE: To estimate the impact of the HIV pandemic on vaccine-acquired
      population immunity to measles virus because high levels of population immunity
      are required to eliminate transmission of measles virus in large geographical
      areas, and HIV infection can reduce the efficacy of measles vaccination. METHODS:
      A literature review was conducted to estimate key parameters relating to the
      potential impact of HIV infection on the epidemiology of measles in sub-Saharan
      Africa; parameters included the prevalence of HIV, child mortality, perinatal HIV
      transmission rates and protective immune responses to measles vaccination. These
      parameter estimates were incorporated into a simple model, applicable to regions
      that have a high prevalence of HIV, to estimate the potential impact of HIV
      infection on population immunity against measles. FINDINGS: The model suggests
      that the HIV pandemic should not introduce an insurmountable barrier to measles
      control and elimination, in part because higher rates of primary and secondary
      vaccine failure among HIV-infected children are counteracted by their high
      mortality rate. The HIV pandemic could result in a 2-3% increase in the
      proportion of the birth cohort susceptible to measles, and more frequent
      supplemental immunization activities (SIAs) may be necessary to control or
      eliminate measles. In the model the optimal interval between SIAs was most
      influenced by the coverage rate for routine measles vaccination. The absence of a
      second opportunity for vaccination resulted in the greatest increase in the
      number of susceptible children. CONCLUSION: These results help explain the
      initial success of measles elimination efforts in southern Africa, where measles
      control has been achieved in a setting of high HIV prevalence.

PMID- 15976874
TI  - Modelling the effectiveness of financing policies to address underutilization of
      children's health services in Nepal.
AB  - OBJECTIVE: To estimate the price responsiveness of utilization of formal
      children's health-care services in Nepal and to use this information to model the
      impact on utilization of subsidies or increases in user fees. METHODS: A total of
      8112 individual observations (of children aged < 15 years) from 2847 households
      in 274 communities were obtained from the 1996 Nepal Living Standards Survey. A
      logit model was applied to determine the net impact of price on a parent or
      caregiver's decision to seek care for a given instance of illness. The model's
      coefficients were used to calculate the price responsiveness of utilization
      decisions. FINDINGS: Parents or caregivers reported that 9.7% of children
      (788/8112) had been ill or injured in the previous month. Parents reported that
      they had sought care in 566 (71.8%) of these cases; care was most frequently
      sought from public providers. The price elasticity of demand for children's
      health-care services in the formal sector was estimated at -0.16. As prices rise,
      the demand curve exhibits continuous and declining price elasticity. Overall, a
      100% subsidy of user fees would increase current utilization rates by 56%, while
      a 100% increase in fees would lead to a drop in utilization of only 12%. The
      differential in utilization across income groups was substantial after changes in
      fees were implemented. CONCLUSION: While the effect of price on the utilization
      of children's health-care services in Nepal is statistically significant, the
      size of the impact is modest. Policies to subsidize fees could increase
      utilization substantially, while fee increases would lead to modest declines in
      utilization and generate increased revenue.

PMID- 15976875
TI  - Differences in prevalence of pre-existing morbidity between injured and non
      injured populations.
AB  - OBJECTIVE: To identify and examine differences in pre-existing morbidity between
      injured and non-injured population-based cohorts. METHODS: Administrative health
      data from Manitoba, Canada, were used to select a population-based cohort of
      injured people and a sample of non-injured people matched on age, gender,
      aboriginal status and geographical location of residence at the date of injury.
      All individuals aged 18-64 years who had been hospitalized between 1988 and 1991
      for injury (International Classification of Diseases, Ninth Edition, Clinical
      Modification (ICD-9-CM) code 800-995) (n = 21 032), were identified from the
      Manitoba discharge database. The matched non-injured comparison group comprised
      individuals randomly selected 1:1 from the Manitoba population registry.
      Morbidity data for the 12 months prior to the date of the injury were obtained by
      linking the two cohorts with all hospital discharge records and physician claims.
      RESULTS: Compared to the non-injured group, injured people had higher Charlson
      Comorbidity Index scores, 1.9 times higher rates of hospital admissions and 1.7
      times higher rates of physician claims in the year prior to the injury. Injured
      people had a rate of admissions to hospital for a mental health disorder 9.3
      times higher, and physician claims for a mental health disorder 3.5 times higher,
      than that of non-injured people. These differences were all statistically
      significant (P < 0.001). CONCLUSION: Injured people were shown to differ from the
      general non-injured population in terms of pre-existing morbidity. Existing
      population estimates of the attributable burden of injury that are obtained by
      extrapolating from observed outcomes in samples of injured cases may overestimate
      the magnitude of the problem.

PMID- 15976876
TI  - Standardized interpretation of paediatric chest radiographs for the diagnosis of
      pneumonia in epidemiological studies.
AB  - BACKGROUND: Although radiological pneumonia is used as an outcome measure in
      epidemiological studies, there is considerable variability in the interpretation
      of chest radiographs. A standardized method for identifying radiological
      pneumonia would facilitate comparison of the results of vaccine trials and
      epidemiological studies of pneumonia. METHODS: A WHO working group developed
      definitions for radiological pneumonia. Inter-observer variability in
      categorizing a set of 222 chest radiographic images was measured by comparing the
      readings made by 20 radiologists and clinicians with a reference reading. Intra
      observer variability was measured by comparing the initial readings of a randomly
      chosen subset of 100 radiographs with repeat readings made 8-30 days later.
      FINDINGS: Of the 222 images, 208 were considered interpretable. The reference
      reading categorized 43% of these images as showing alveolar consolidation or
      pleural effusion (primary end-point pneumonia); the proportion thus categorized
      by each of the 20 readers ranged from 8% to 61%. Using the reference reading as
      the gold standard, 14 of the 20 readers had sensitivity and specificity of > 0.70
      in identifying primary end-point pneumonia; 13 out of 20 readers had a kappa
      index of > 0.6 compared with the reference reading. For the 92 radiographs deemed
      to be interpretable among the 100 images used for intra-observer variability, 19
      out of 20 readers had a kappa index of > 0.6. CONCLUSION: Using standardized
      definitions and training, it is possible to achieve agreement in identifying
      radiological pneumonia, thus facilitating the comparison of results of
      epidemiological studies that use radiological pneumonia as an outcome.

PMID- 15976877
TI  - Re-evaluating the burden of rabies in Africa and Asia.
AB  - OBJECTIVE: To quantify the public health and economic burden of endemic canine
      rabies in Africa and Asia. METHODS: Data from these regions were applied to a set
      of linked epidemiological and economic models. The human population at risk from
      endemic canine rabies was predicted using data on dog density, and human rabies
      deaths were estimated using a series of probability steps to determine the
      likelihood of clinical rabies developing in a person after being bitten by a dog
      suspected of having rabies. Model outputs on mortality and morbidity associated
      with rabies were used to calculate an improved disability-adjusted life year
      (DALY) score for the disease. The total societal cost incurred by the disease is
      presented. FINDINGS: Human mortality from endemic canine rabies was estimated to
      be 55 000 deaths per year (90% confidence interval (CI) = 24 000-93 000). Deaths
      due to rabies are responsible for 1.74 million DALYs lost each year (90% CI =
      0.75-2.93). An additional 0.04 million DALYs are lost through morbidity and
      mortality following side-effects of nerve-tissue vaccines. The estimated annual
      cost of rabies is USD 583.5 million (90% CI = USD 540.1-626.3 million). Patient
      borne costs for post-exposure treatment form the bulk of expenditure, accounting
      for nearly half the total costs of rabies. CONCLUSION: Rabies remains an
      important yet neglected disease in Africa and Asia. Disparities in the
      affordability and accessibility of post-exposure treatment and risks of exposure
      to rabid dogs result in a skewed distribution of the disease burden across
      society, with the major impact falling on those living in poor rural communities,
      in particular children.

PMID- 15976878
TI  - Does the Integrated Management of Childhood Illness cost more than routine care?
      Results from the United Republic of Tanzania.
AB  - OBJECTIVE: The Integrated Management of Childhood Illness (IMCI) strategy is
      designed to address the five leading causes of childhood mortality, which
      together account for 70% of the 10 million deaths occurring among children
      worldwide annually. Although IMCI is associated with improved quality of care,
      which is a key determinant of better health outcomes, it has not yet been widely
      adopted, partly because it is assumed to be more expensive than routine care.
      Here we report the cost of IMCI compared with routine care in four districts in
      the United Republic of Tanzania. METHODS: Total district costs of child care were
      estimated from the societal perspective as the sum of child health-care costs
      incurred in a district at the household level, primary health-facility level and
      hospital level. We also included administrative and support costs incurred by
      national and district administrations. The incremental cost of IMCI is the
      difference in costs of child health-care between districts with and without IMCI,
      after standardization for population size. FINDINGS: The annual cost per child of
      caring for children less than five years old in districts with IMCI was USD
      11.19, 44% lower than the cost in the districts without IMCI (USD 16.09). Much of
      the difference was due to higher rates of hospitalization of children less than 5
      years old in the districts without IMCI. Not all of this difference can be
      attributed to IMCI but even when differences in hospitalization rates are
      excluded, the cost per child was still 6% lower in IMCI districts. CONCLUSION:
      IMCI was not associated with higher costs than routine child health-care in the
      four study districts in the United Republic of Tanzania. Given the evidence of
      improved quality of care in the IMCI districts, the results suggest that cost
      should not be a barrier to the adoption and scaling up of IMCI.

PMID- 15976879
TI  - The future of the HIV pandemic.
AB  - The emerging HIV epidemics in countries of Asia and Eastern Europe will
      contribute significantly to the future of the HIV pandemic. Forecasts of the
      scale of these epidemics are subject to massive uncertainty, however, mainly
      because of the sensitivity of predictions to small alterations in parameters that
      are difficult to estimate. In most of these countries, HIV is currently
      concentrated among vulnerable populations such as injecting drug users, sex
      workers and their clients, or men who have sex with men. This distribution
      suggests an alternative to disease forecasting based on the techniques of risk
      assessment routinely used by environmental epidemiologists. Exposure mapping,
      dose-response curves and the concept of acceptable risk are some of the tools
      that may be useful for HIV risk management. This approach is illustrated by a
      description of exposure in Indonesia and an assessment of currently accepted risk
      of death for different causes including HIV in the Russian Federation. Although
      inappropriate for forecasts of heterosexual HIV transmission, mathematical models
      are shown to be useful for making qualitative predictions about the relative
      importance of different behaviours for the spread of HIV over time and for
      interpreting observed trends in HIV prevalence from sentinel surveillance sites.

PMID- 15976880
TI  - New approaches to effectively programming HIV/AIDS prevention resources.

PMID- 15976881
TI  - Monitoring equity in immunization coverage.
AB  - This paper analyses trends in coverage of three doses of diphtheria-pertussis
      tetanus vaccine (DPT3) by wealth groups in selected countries. It discusses the
      depth of disparities in coverage by wealth and changes during the 1990s. Complete
      assessment of equity in income and its trends have been discussed in other
      papers, however issues related to children's well-being have often been brushed
      aside because the comparable data needed to fully understand and rectify
      inequalities is lacking. A focal point of this paper pertains to gathering any
      and all information recorded about the immunization of children and then
      transcribing these data so that it is applicable to all countries. We analyse the
      technical difficulties and methodological solutions that would enable comparisons
      to be made between various measures of inequity taken from different surveys at
      two or three points in time among a variety of subpopulations in order to obtain
      disaggregated data. This paper argues for a simultaneous analysis of changes in
      averages and disparities in immunization coverage along variables of interest,
      such as wealth, gender and place of residence in order to achieve a better
      understanding of trends. We also focus on measurement issues and describe trends
      in immunization by wealth. We conclude with a brief discussion of issues related
      to monitoring equitable outcomes and offer suggestions for further research. In
      addition, the paper presents some lessons that can be drawn about monitoring and
      policies. We hope that this analysis of patterns of disparities will help policy
      makers in devising, proposing and executing efficient policies and interventions.

PMID- 15976882
TI  - Time for an additional paradigm? The community-based catalyst approach to public
      health.

PMID- 15976883
TI  - Availability of miltefosine for the treatment of kala-azar in India.

PMID- 15976884
TI  - One-journal-for-MEDLINE initiative in Nepal.

PMID- 15976885
TI  - Exclusion, inequity and health system development: the critical emphases for
      maternal, neonatal and child health.

PMID- 15976886
TI  - Strengthening district health systems.

PMID- 15976887
TI  - Regional associations of medical journal editors: moving from rhetoric to
      reality.

PMID- 15976888
TI  - Tsunami wreaks mental health havoc.

PMID- 15976889
TI  - Fighting chronic disease.

PMID- 15976891
TI  - No cry at birth: global estimates of intrapartum stillbirths and intrapartum
      related neonatal deaths.
AB  - OBJECTIVE: Fewer than 3% of 4 million annual neonatal deaths occur in countries
      with reliable vital registration (VR) data. Global estimates for asphyxia-related
      neonatal deaths vary from 0.7 to 1.2 million. Estimates for intrapartum
      stillbirths are not available. We aimed to estimate the numbers of intrapartum
      related neonatal deaths and intrapartum stillbirths in the year 2000. METHODS:
      Sources of data on neonatal death included: vital registration (VR) data on
      neonatal death from countries with full (> 90%) VR coverage (48 countries, n =
      97,297); studies identified through literature searches (> 4000 abstracts) and
      meeting inclusion criteria (46 populations, 30 countries, n = 12,355). A
      regression model was fitted to cause-specific proportionate mortality data from
      VR and the literature. Predicted cause-specific proportions were applied to the
      number of neonatal deaths by country, and summed to a global total. Intrapartum
      stillbirths were estimated using median cause-specific mortality rate by country
      (73 populations, 52 countries, n = 46,779) or the subregional median in the
      absence of country data. FINDINGS: Intrapartum-related neonatal deaths were
      estimated at 0.904 million (uncertainty 0.65-1.17), equivalent to 23% of the
      global total of 4 million neonatal deaths. Country-level model predictions
      compared well with population-based data sets not included in the input data. An
      estimated 1.02 million intrapartum stillbirths (0.66-1.48 million) occur
      annually, comprising 26% of global stillbirths. CONCLUSION: Intrapartum-related
      neonatal deaths account for almost 10% of deaths in children aged under 5 years.
      Intrapartum stillbirths are a huge and invisible problem, but are potentially
      preventable. Programmatic attention and improved information are required.

PMID- 15976892
TI  - Infant feeding patterns and risks of death and hospitalization in the first half
      of infancy: multicentre cohort study.
AB  - OBJECTIVE: To determine the association of different feeding patterns for infants
      (exclusive breastfeeding, predominant breastfeeding, partial breastfeeding and no
      breastfeeding) with mortality and hospital admissions during the first half of
      infancy. METHODS: This paper is based on a secondary analysis of data from a
      multicentre randomized controlled trial on immunization-linked vitamin A
      supplementation. Altogether, 9424 infants and their mothers (2919 in Ghana, 4000
      in India and 2505 in Peru) were enrolled when infants were 18-42 days old in two
      urban slums in New Delhi, India, a periurban shanty town in Lima, Peru, and 37
      villages in the Kintampo district of Ghana. Mother-infant pairs were visited at
      home every 4 weeks from the time the infant received the first dose of oral polio
      vaccine and diphtheria-pertussis-tetanus at the age of 6 weeks in Ghana and India
      and at the age of 10 weeks in Peru. At each visit, mothers were queried about
      what they had offered their infant to eat or drink during the past week.
      Information was also collected on hospital admissions and deaths occurring
      between the ages of 6 weeks and 6 months. The main outcome measures were all
      cause mortality, diarrhoea-specific mortality, mortality caused by acute lower
      respiratory infections, and hospital admissions. FINDINGS: There was no
      significant difference in the risk of death between children who were exclusively
      breastfed and those who were predominantly breastfed (adjusted hazard ratio (HR)
      = 1.46; 95% confidence interval (CI) = 0.75-2.86). Non-breastfed infants had a
      higher risk of dying when compared with those who had been predominantly
      breastfed (HR = 10.5; 95% CI = 5.0-22.0; P < 0.001) as did partially breastfed
      infants (HR = 2.46; 95% CI = 1.44-4.18; P = 0.001). CONCLUSION: There are two
      major implications of these findings. First, the extremely high risks of infant
      mortality associated with not being breastfed need to be taken into account when
      informing HIV-infected mothers about options for feeding their infants. Second,
      our finding that the risks of death are similar for infants who are predominantly
      breastfed and those who are exclusively breastfed suggests that in settings where
      rates of predominant breastfeeding are already high, promotion efforts should
      focus on sustaining these high rates rather than on attempting to achieve a shift
      from predominant breastfeeding to exclusive breastfeeding.

PMID- 15976893
TI  - Chest X-ray-confirmed pneumonia in children in Fiji.
AB  - OBJECTIVE: To calculate the incidence and document the clinical features of chest
      X-ray- (CXR-) confirmed pneumonia in children aged between 1 month and 5 years
      living in Greater Suva, Fiji. METHODS: A retrospective review was undertaken of
      children aged between 1 month and 5 years with a discharge diagnosis suggesting a
      lower respiratory tract infection (LRTI) admitted to the Colonial War Memorial
      Hospital in Suva, Fiji, in the first 10 days of each month from 1 January 2001 to
      31 December 2002. Clinical data were collected and CXRs were reread and
      classified according to WHO standardized criteria for CXR-confirmed pneumonia.
      FINDINGS: Two hundred and forty-eight children with LRTI met the inclusion
      criteria. CXRs were obtained for 174 (70%) of these cases, of which 59 (34%) had
      CXR-confirmed pneumonia. The annual incidence of CXR-confirmed pneumonia was 428
      cases per 100,000 children aged between 1 month and 5 years living in Greater
      Suva. If a similar proportion of the children for whom CXRs were unavailable were
      assumed to have CXR-confirmed pneumonia, the incidence was 607 per 100,000. The
      incidence appeared to be higher in Melanesian Fijian than Indo-Fijian children.
      The case-fatality rate was 2.8% in all children with LRTI, and 6.8% in those with
      CXR-confirmed pneumonia. CONCLUSION: This is the first study to document the
      incidence of CXR-confirmed pneumonia in a Pacific Island country, and
      demonstrates a high incidence. A significant proportion of hospital admissions of
      children with LRTI are likely to be preventable by the introduction of
      pneumococcal conjugate vaccine.

PMID- 15976894
TI  - Operational and economic evaluation of an NGO-led sexually transmitted infections
      intervention: north-western Cambodia.
AB  - OBJECTIVE: Sexually transmitted infection (STI) services were offered by the
      nongovernmental organization Medecins Sans Frontieres-Holland in Banteay Meanchey
      province, Cambodia, between 1997 and 1999. These services targeted female sex
      workers but were available to the general population. We conducted an evaluation
      of the operational performance and costs of this real-life project. METHODS:
      Effectiveness outcomes (syndromic cure rates of STIs) were obtained by
      retrospectively analysing patients' records. Annual financial and economic costs
      were estimated from the provider's perspective. Unit costs for the cost
      effectiveness analysis included the cost per visit, per partner treated, and per
      syndrome treated and cured. FINDINGS: Over 30 months, 11,330 patients attended
      the clinics; of these, 7776 (69%) were STI index patients and only 1012 (13%)
      were female sex workers. A total of 15 269 disease episodes and 30 488 visits
      were recorded. Syndromic cure rates ranged from 39% among female sex workers with
      genital ulcers to 74% among men with genital discharge; there were variations
      over time. Combined rates of syndromes classified as cured or improved were
      around 84-95% for all syndromes. The total economic costs of the project were US
      766,046 dollars. The average cost per visit over 30 months was US 25.12 dollars
      and the cost per partner treated for an STI was US 50.79 dollars. The average
      cost per STI syndrome treated was US 48.43 dollars, of which US 4.92 dollars was
      for drug treatment. The costs per syndrome cured or improved ranged from US 46.95
      153.00 dollars for men with genital ulcers to US 57.85-251.98 dollars for female
      sex workers with genital discharge. CONCLUSION: This programme was only partly
      successful in reaching its intended target population of sex workers and their
      male partners. Decreasing cure rates among sex workers led to relatively poor
      cost-effectiveness outcomes overall despite decreasing unit costs.

PMID- 15976895
TI  - Has the burden of depression been overestimated?
AB  - OBJECTIVE: To investigate whether high estimates of the burden of depression
      could be attributed to an overestimation of disability weights (reflecting more
      severe disability). METHODS: We derived disability weights that were tailored to
      prevalence data. Empirical disability data from a Dutch community survey was used
      to describe three classes of severity of depression and their proportional
      prevalence. We obtained valuations from experts for each class and calculated the
      overall disability weight for depression. FINDINGS: Expert valuations were
      similar to those of previous studies. The overall disability weight for
      depression was similar to other studies except the 1994 Dutch Burden of Disease
      Calculation, which it exceeded by 73%. The lower Dutch 1994 disability weight
      resulted from an overestimation of the proportion of mild cases of depression by
      experts (60% versus 27% observed in the empirical data used in the present
      study). CONCLUSION: This study found no indication that disability associated
      with depression was overestimated. The Dutch example showed the importance of
      tailoring disability weights to epidemiological data on prevalence.

PMID- 15976896
TI  - Reliability of data on caesarean sections in developing countries.
AB  - OBJECTIVE: To examine the reliability of reported rates of caesarean sections
      from developing countries and make recommendations on how data collection for
      surveys and health facility-based studies could be improved. METHODS: Population
      based rates for caesarean section obtained from two sources: Demographic and
      Health Surveys (DHS) and health facility-based records of caesarean sections from
      the Unmet Obstetric Need Network, together with estimates of the number of live
      births, were compared for six developing countries. Sensitivity analyses were
      conducted using several different definitions of the caesarean section rate, and
      the rates obtained from the two data sources were compared. FINDINGS: The DHS
      rates for caesarean section were consistently higher than the facility-based
      rates. However, in three quarters of the cases, the facility-based rates for
      caesarean sections fell within the 95% confidence intervals for the DHS estimate.
      CONCLUSION: The importance of the differences between these two series of rates
      depends on the analyst's perspective. For national and global monitoring, DHS
      data on caesarean sections would suffice, although the imprecision of the rates
      would make the monitoring of trends difficult. However, the imprecision of DHS
      data on caesarean sections precludes their use for the purposes of programme
      evaluation at the regional level.

PMID- 15976897
TI  - The costs of home delivery of a birth dose of hepatitis B vaccine in a prefilled
      syringe in Indonesia.
AB  - OBJECTIVE: To provide global policy-makers with decision-making information for
      developing strategies for immunization of infants with a birth dose of hepatitis
      B vaccine, this paper presents a retrospective cost analysis, conducted in
      Indonesia, of delivering this vaccine at birth using the Uniject prefill
      injection device. METHODS: Incremental costs or cost savings associated with
      changes in the hepatitis B immunization programme were calculated using
      sensitivity analysis to vary the estimates of vaccine wastage rates and prices
      for vaccines and injection devices, for the birth dose of hepatitis B vaccine.
      FINDINGS: The introduction of hepatitis B vaccine prefilled in Uniject (HB
      Uniject) single-dose injection devices for use by midwives for delivering the
      birth dose is cost-saving when the wastage rate for multidose vials is greater
      than 33% (Uniject is a trademark of BD, Franklin Lakes, NJ, USA). CONCLUSION: The
      introduction of HB-Uniject for birth-dose delivery is economically worthwhile and
      can increase coverage of the critical birth dose, improve resource utilization,
      reduce transmission of hepatitis B and promote injection safety.

PMID- 15976898
TI  - National maternal mortality ratio in Egypt halved between 1992-93 and 2000.
AB  - Two surveys of maternal mortality conducted in Egypt, in 1992-93 and in 2000,
      collected data from a representative sample of health bureaus covering all of
      Egypt, except for five frontier governorates which were covered only by the later
      survey, using the vital registration forms. The numbers of maternal deaths were
      determined and interviews conducted. The medical causes of death and avoidable
      factors were determined. Results showed that the maternal mortality ratio (MMR)
      had dropped by 52% within that period (from 174 to 84/100,000 live births). The
      National Maternal Mortality Survey in 1992-93 (NMMS) revealed that the
      metropolitan areas and Upper Egypt had a higher MMR than Lower Egypt. In response
      to these results, the Egyptian Ministry of Health and Population (MOHP)
      intensified the efforts of its Safe Motherhood programmes in Upper Egypt with the
      result that the regional situation had reversed in 2000. Consideration of the
      intermediate and outcome indicators suggests that the greatest effect of maternal
      health interventions was on the death-related avoidable factors "substandard care
      by health providers" and "delays in recognizing problems or seeking medical
      care". The enormous improvements in these areas are certainly due in part to
      extensive training, revised curricula, the publication of medical protocols and
      services standards, the upgrading of facilities, and successful community
      outreach programmes and media campaigns. The impact on the utilization of
      antenatal care (ANC) has been less successful. Other areas that remain
      problematic are inadequate supplies of blood, drugs and equipment. Although the
      number of maternal deaths linked to haemorrhage has been drastically reduced, it
      remains the primary cause. The drop in maternal mortality in the 1990s in
      response to Safe Motherhood programmes was impressive and the ability to tailor
      interventions based on the data from the NMMS of 1992-93 and 2000 was clearly
      demonstrated. To ensure the continuing availability of information to guide and
      evaluate programmes for reducing maternal mortality, an Egyptian national
      maternal mortality surveillance system is being developed.

PMID- 15976899
TI  - Institutionalizing policy-level health impact assessment in Europe: is coupling
      health impact assessment with strategic environmental assessment the next step
      forward?
AB  - European Union (EU) Member States are interested in using health impact
      assessment (HIA) as a means of safeguarding their obligations to protect human
      health under the 1997 Treaty of Amsterdam. However, several have encountered
      difficulties institutionalizing HIA with the policy-making process. As a
      consequence, the World Health Organization (WHO) Regional Office for Europe has
      suggested coupling HIA with strategic environmental assessment (SEA).
      Traditionally, the incorporation of HIA into other forms of impact assessment has
      been resisted, for fear of losing its focus on health issues to environmental
      concerns, and compromising its social model of health with the introduction of
      biophysical indicators. But can these fears be substantiated? In this paper, we
      investigate the grounds for such concerns by reviewing the relevant policy
      documents and departmental guidelines of four non-European countries that have
      considered the use of integrated assessment. We found that the case for
      associating HIA with SEA in Europe is strong, and offers potential solutions to
      problems of screening, theoretical framework, causal pathways and ready entry to
      the policy process. Coupling HIA with SEA may thus be the next step forward in a
      longer journey towards institutionalizing HIA as an independent policy-linked
      device.

PMID- 15976900
TI  - Making systematic reviews more useful for policy-makers.

PMID- 15976902
TI  - [Colorectal cancer: the importance of its prevention].

PMID- 15976903
TI  - [Endoscopic retrograde cholangiopancreatography can be performed safely in
      ambulatory centers].
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography is effective technique
      to approach various biliary and pancreatic disorders. Safety of endoscopic
      retrograde cholangiopancreatography on an outpatient basis has been questioned.
      OBJECTIVES: To evaluate the safety of outpatient endoscopic retrograde
      cholangiopancreatography and describe procedure complications. PATIENTS/METHOD:
      We prospectively assessed outpatients endoscopic retrograde
      cholangiopancreatography during 2001 to 2003 period. Complications were defined
      according to consensus criteria and all adverse effects related to procedure were
      included. RESULTS: One hundred and ninety five outpatients endoscopic retrograde
      cholangiopancreatography were performed, 79 (40.5%) diagnostic and 116 (59.5%)
      therapeutic. The study group included 112 women, mean age 51 (+/- 18.9) years.
      The most common diagnoses were: biliary calculi (30.2%), benign stenosis,
      (13.8%), malignant obstruction (10.2%) and chronic pancreatitis (10.2%). Success
      was achieved in 88.6% of diagnostic endoscopic retrograde
      cholangiopancreatography and 78.5% in therapeutic. Complications necessitating
      observation developed in 10 (5.1%) of 195 endoscopic retrograde
      cholangiopancreatography, among them, 7 (3.6%) were hospitalized, (2 acute
      pancreatitis, 2 perforations, 1 bleeding, 1 cardio-respiratory e 1 fever). Among
      188 patients initially discharged 8 (4.2%) needed readmission (1 acute
      pancreatitis, 1 bleeding, 1 perforation, 3 cholangitis, 2 abdominal pain).
      Comparing the first group where complications were immediately identified to the
      second, no significant statistical difference concerning to age, sex, diagnoses
      and procedure difficulty degree was found. CONCLUSION: Sample size and negative
      statistical results failed to determinate independent risk factors for
      outpatients endoscopic retrograde cholangiopancreatography complications.
      However, there were no deaths or bad evolution in patients released after
      examination, confirming the safety of outpatient endoscopic retrograde
      cholangiopancreatography.

PMID- 15976904
TI  - Proximal and distal esophageal contractions in patients with vigorous or classic
      esophageal Chagas' disease.
AB  - BACKGROUND: Some patients with achalasia have distal esophageal contraction
      amplitude in the normal range, a condition called vigorous achalasia, and others
      have low contraction amplitude, a condition named classic achalasia. The
      difference in distal contraction amplitude may also be associated with a
      difference in proximal contraction amplitude. AIM: To study the proximal and
      distal esophageal contractions in patients with Chagas' disease. MATERIAL AND
      METHODS: We studied 28 patients with Chagas' disease, all with dysphagia and an
      esophageal radiologic examination with retention without dilation, and 18
      controls. The patients with Chagas' disease had vigorous achalasia (distal
      amplitude over 34 mm Hg, n = 13) or classic achalasia (distal amplitude below 34
      mm Hg, n = 15). We measured the contractions by the manometric method with
      continuous perfusion at 2, 7, 12 and 17 cm below the upper esophageal sphincter
      after five swallows of a 5 mL bolus of water. RESULTS: There was no difference in
      proximal amplitude of contractions between classic or vigorous achalasia, and
      controls. In the proximal esophagus there was also no difference in duration or
      area under curve of contractions. In the distal esophagus, duration and area
      under curve were lower in classic than vigorous disease. Failed and simultaneous
      contractions were more frequent in patients than controls. Simultaneous
      contractions were seen more frequently in classic disease, and peristaltic
      contractions were seen more frequently in vigorous disease. CONCLUSION: We did
      not find differences in proximal esophageal contractions of patients with
      classical or vigorous esophageal Chagas' disease, except for the higher number of
      simultaneous contractions seen in classic disease.

PMID- 15976905
TI  - Benign obstruction of the common hepatic duct (Mirizzi syndrome): diagnosis and
      operative management.
AB  - BACKGROUND: Mirizzi syndrome is a rare complication of prolonged cholelithiasis,
      characterized by narrowing of the common hepatic duct due to mechanical
      compression and/or inflammation due to biliary calculus impacted in the
      infundibula of the gallbladder or in the cystic duct. OBJECTIVES: To describe a
      series of eight consecutive patients with Mirizzi syndrome, at a single
      institution, submitted to surgical treatment and to comment on their aspects with
      emphasis on the diagnosis and treatment. METHODS: Four women and four men, with a
      mean age of 61.6 years (42 to 82 years), presenting Mirizzi syndrome were
      operated between 1997 and 2003. The following items were evaluated: clinical
      presentation, laboratory results, preoperative evaluation, operative findings,
      presence of choledocholithiasis, type of Mirizzi syndrome according to the
      classification by Csendes, choice of operative procedures, and complications.
      RESULTS: The most frequent symptoms were abdominal pain (87.5%) and jaundice
      (87.5%). All the patients presented altered hepatic function tests. The diagnosis
      of Mirizzi syndrome was intra-operative in seven (87.5%) patients, and
      preoperative in one (12.5%). Cholecystocholedochal fistula associated with
      choledocholithiasis was observed in three (37.5%) cases. Mirizzi syndrome was
      classified as Csendes type I in five (62.5%) patients, type II in one (12.5%),
      type III in one (12,5%) and type IV in another (12.5%). Cholecystectomy, as an
      isolated surgical procedure, was performed in four (50.0%) patients. One (12.5%)
      patient was submitted to partial cholecystectomy and closure of the fistulous
      orifice with the central part of the infundibula. Two (25.0%) patients were
      submitted to cholecystectomy and side-to-side choledochoduodenostomy and another
      (12.5%) to side-to-side choledochoduodenostomy remaining the gallbladder in situ.
      Seven (87.5%) patients had an uneventful recovery and were discharged in good
      conditions. One (12.5%) patient presented a postoperative sepsis due to a sub
      hepatic abscess, and was reoperated. There was no operative mortality.
      CONCLUSION: The preoperative diagnosis of Mirizzi syndrome is difficult and an
      awarded suspicion is necessary to avoid lesions of the biliary tree. The problem
      may only become evident during the operation due to firm adherences around
      Calot's triangle. The success of the treatment is related to a precocious
      recognition of the condition, even at the time of surgery, and adapting the
      management considering to the individual characteristics of each case.

PMID- 15976906
TI  - Amplitude and recovery velocity of relaxation induced by rectoanal inhibitory
      reflex and its importance for obstructive evacuation.
AB  - BACKGROUND: The rectoanal inhibitory reflex has an important rule in the fecal
      continence mechanism. Alterations in this reflex can be associated with
      compromised anal sphincteric function. AIM: To identify possible correlation
      between rectoanal inhibitory reflex parameters and intestinal constipation due to
      obstructive evacuation. PATIENTS: Sixty nine patients with intestinal
      constipation had been submitted to anorectal manometry. It was selected 29
      patients (27 female, mean age of 42.3 (19-73) years) having intestinal
      constipation owing to obstructive evacuation. Thirteen individuals without
      anorectal functional complaints (eight female, mean age 52.5 (28-73) years)
      formed the control group. RESULTS: The mean value of resting anal pressure before
      rectoanal inhibitory reflex in the proximal and distal anal canals were 61.8 mm
      Hg and 81.7 mm Hg respectively, for the constipated patients, and 46.0 mm Hg and
      64.5 mm Hg, respectively, for asymptomatic individuals. The mean pressure at the
      point of maximal relaxation in constipated patients was 29.0 mm Hg in the
      proximal anal canal, and 52.1 mm Hg in the distal anal canal, whilst in the
      asymptomatic group they were 17.8 mm Hg and 36.3 mm Hg, respectively. The mean
      percentage difference between the mean resting anal pressure and the mean point
      of maximal relaxation pressure in the proximal anal canal (amplitude of
      relaxation) was 54.1% in constipated patients and 54.3% in asymptomatic
      individuals. In the distal anal canal it was, respectively, 35.6% in constipated
      patients, and 38.5% in the control group. The average recovery velocity of
      relaxation in the proximal anal canal was 4.06 mm/second in constipated patients
      and 2.98 mm/second in asymptomatic individuals, giving a significant difference
      between the two groups, as well as in the distal anal canal (3.9 mm/second and
      2.98 mm/second, respectively) CONCLUSION: The greater recovery velocity of the
      resting anal pressure in the proximal anal canal in constipated patients than in
      controls may be associated with obstructive evacuation.

PMID- 15976907
TI  - [Prevalence and factors associated with intestinal constipation in postmenopausal
      women].
AB  - BACKGROUND: Constipation occurs more frequently in the female population and it
      becomes more prevalent with increasing age. There are few studies that have
      assessed the prevalence of constipation in postmenopausal women. AIM: To
      investigate the prevalence and factors associated with constipation in
      postmenopausal women. PATIENTS AND METHODS: A cross-sectional study of
      postmenopausal women aged over 45 years was conducted. It included 100 women who
      sought medical attention at the Menopause Outpatient Facility at the State
      University of Campinas (UNICAMP), Campinas, SP, Brazil, between March, 2003 and
      January, 2004. The prevalence of constipation was assessed according to the Rome
      II criteria. Sociodemographic and clinical features of these patients were
      studied. Physical examinations were performed to evaluate genital dystopias and
      anal sphincter tone. Statistical analysis was performed by using the mean,
      standard deviation, median, relative and absolute frequencies and by using the
      prevalence ratio with a 95% confidence interval and multiple logistic regression.
      RESULTS: The mean age of the participants was 58.9 +/- 5.9 years and the mean age
      was 47.5 +/- 5.4 years at menopause. The prevalence of constipation was 37%, the
      most common symptom being excessive straining when defecating (91.9%), followed
      by a feeling of incomplete evacuation (83.8%), hard or lumpy stools (81.1%), less
      than three bowel movements per week (62.2%), sensation of anorectal obstruction
      during defecation (62.2%) and digital maneuvers to facilitate defecation (45.9%).
      Bivariate analysis showed that anal sphincter tone and the history of perianal
      surgery were factors associated with constipation. After applying multiple
      regression analysis, the history of perianal surgery was significantly associated
      with constipation (prevalence ratio: 2.68; 95% confidence interval: 1.18-6.11).
      CONCLUSIONS: The prevalence of constipation in postmenopausal women was high. The
      history of perianal surgery was significantly associated with constipation, even
      when the influence of other variables were taken into consideration.

PMID- 15976908
TI  - Cell proliferation and apoptosis in gastric cancer and intestinal metaplasia.
AB  - BACKGROUND: Higher proliferation is commonly observed in cancer cells. Apoptosis
      can be a useful measure of a tumor cell kinetic. Alteration of the balance
      between proliferation and apoptosis is associated with cancer. AIM: To study
      proliferation and apoptosis on gastric cancer and in intestinal metaplasia.
      METHODOLOGY: Twenty-two samples from gastric adenocarcinomas and 22 biopsies from
      intestinal metaplasia were studied. The apoptotic bodies in hematoxylin-eosin
      slides and the expression of p53, bcl-2 and Ki67 were determined by
      immunohistochemistry. RESULTS: The number of the apoptotic cells was higher in
      cancer. Ki 67LI increased from intestinal metaplasia to gastric cancer. p53 was
      positive in 68% of the patients with cancer, more frequently in advanced stage
      and negative in samples of intestinal metaplasia. Although there was no
      significant difference between the groups, bcl-2 was positive in 45% of gastric
      cancer tissue and in 68% of metaplasia. In gastric cancer patients bcl-2 was
      expressed in early gastric cancer more frequently than in advanced stage.
      CONCLUSION: The positivity of bcl-2 was higher in metaplasia and probably is
      involved in the progression of carcinogenesis. p53 was negative in metaplasia and
      positive in more than half of the gastric cancer, mostly in stage IV, suggesting
      a late event in gastric cancer.

PMID- 15976909
TI  - [Correlation between platelet blood levels and the hepatic venous pressure
      gradient among patients with cirrhosis].
AB  - BACKGROUND: Determination of hepatic venous pressure gradient is the main method
      used to assess portal pressure. Recently, platelet blood levels has been
      indicated as a non-invasive marker of the presence of portal hypertension. AIM:
      To correlate platelet blood levels with the hepatic venous pressure gradient
      among patients with cirrhosis. PATIENTS AND METHODS: A total of 83 cirrhotic
      patients who had undergone hepatic venous pressure gradient over the last 6 years
      were included. Patients were divided in groups according to Child-Pugh
      classification. All had upper digestive endoscopy to assess the presence of
      esophageal varices and platelet serum levels were recorded. RESULTS: Platelet
      serum levels range varied between 45,000/mm(3) and 389,000/mm(3) (mean: 104,099;
      standard deviation: 58,776). Mean hepatic venous pressure gradient was 15.2 mm Hg
      with a standard deviation of 6.4 mm Hg (range: 1 to 29 mm Hg). Simple linear
      regression analysis was applied to verify an association of hepatic venous
      pressure gradient and platelet serum levels, revealing a weak correlation between
      both variables. We observed a progressive reduction of serum platelet levels as
      esophageal varices diameter increased and hepatocellular function (established by
      Child-Pugh classification) decreased. However, these findings did not reach
      statistical significance. CONCLUSION: Despite the lack of a statistical
      significant correlation among serum platelet levels and hepatic venous pressure
      gradient or hepatocellular function, there was a clear tendency indicating that
      those variables could be involved in the pathogenesis of low platelet levels.

PMID- 15976910
TI  - [Alogenic islet transplantation on the rat liver after alogenic dendritic cells
      injection in the thymus].
AB  - BACKGROUND: The major indication for pancreas or islet transplantation is
      diabetes mellitus type I. This process has to supply the insulin necessity
      keeping glucose under control. AIM: We studied alogenic islet transplantation on
      the rat liver, Wistar (RT1u) to Lewis (RT1(1)) as a recipient. Control group (n =
      8) and dendritic cell group (n = 9) respectively with injection of Hanks solution
      and dendritic cells in the thymus before islet transplantation. MATERIAL AND
      METHODS: With the method of isolation and purification of the islets we obtained
      both in the control group 3637 +/- 783,3 islets with purity of 85 +/- 3,52% and
      dendritic cell group 3268 +/- 378 islets with purity of 87 +/- 4,47%. The
      dendritic cells were retrieved from the spleen and we obtained 3,34 x 105+/-1,16
      cells. Diabetes was induced by i.v. streptozotocin. RESULTS: Control group the
      transplantation of 3637 +/- 783,3 islets in the rat liver normalized glucose
      test, 7,21 +/- 0,57 mmol/L in the second post-operative day. Acute rejection came
      in the 10 postoperative day with significantly increase of glucose test.
      Dendritic cell group, the transplantation of 3258 +/- 378 islets in the rat
      liver, normalized the glucose test was 9,3 +/- 2,85 mmoL/L in the second
      postoperative day. From the 4th postoperative day to 10th postoperative day the
      glucose test increase significantly showing an early acute rejection. CONCLUSION:
      The injection of dendritic cells in the thymus before alogenic islet
      transplantation in the rat liver lead to an early acute rejection.

PMID- 15976911
TI  - [Inhibition of abdominal abscess formation in rat: mortality by sepsis].
AB  - BACKGROUND: Intra-abdominal abscesses and adhesions play important roles on
      isolation of a septic process and on organism protection against bacteremia. On
      the other hand, such phenomenon difficults the afflux of immune factors and
      antibiotics to the septic site. The purpose of the present study was to evaluate
      the effect of abscess inhibition on survival of abdominal sepsis. METHODS: Thirty
      adult Wistar rats were submitted to intraperitoneal injection of 50% rat feces
      solution. The animals were divided into three groups (n = 10). Group 1: control -
      feces solution; group 2: feces solution plus 0.9% saline solution; and group 3:
      feces solution plus 1% carboxymethylcellulose to inhibit abdominal adhesions. The
      three groups were divided into two subgroups (n = 5). Subgroup A: relaparorotomy
      after 4 days and investigation of the abdominal cavity; and subgroup B: follow-up
      during 30 days to evaluate the mortality and its cause. The Fisher test was
      utilized for statistical analyses. RESULTS: The injection of 0.9% saline solution
      did not increase the mortality of the rats. However, the mortality enhanced in
      the group that received carboxymethylcellulose comparing with control group. That
      group developed less adhesions and abscesses. CONCLUSION: This study demonstrated
      that the reduction of abscess formation and of intraperitoneal adhesions
      increases the mortality due to abdominal septic disease.

PMID- 15976912
TI  - [Experimental acute pancreatitis induced by L-arginine: a histological and
      biochemical evaluation].
AB  - BACKGROUND: Excessive doses of basic amino acids such as L-arginine are able to
      injure the pancreas of rats. AIM: To describe and evaluate the biochemical and
      histological characteristics of acute pancreatitis in rats induced by L-arginine
      during the installation, development and repair stages of the pancreatic
      inflammatory process. MATERIAL AND METHODS - The study group consisted of 105
      male Wistar rats. The rats in the experimental group (n = 70) received 500 mg/100
      g of corporal weight L-arginine injection intraperitoneally. In the control group
      (n = 35), isotonic saline solution was injected. Ten rats in the experiment group
      and five in the control group were analyzed after 6, 12, 24, 48, and 72 hours, on
      the 7th and 14th days. During those times, blood samples were collected for
      laboratory testing and samples from the pancreas were collected for an optical
      microscopy analysis. RESULTS: From 12 to 24 hours after the injection of L
      arginine, the amylase serum levels raised to their peak values when compared to
      the rats in the control group, decreasing gradually, reaching an equal level
      after the 48th hour and being significantly lower after 72 hours and 7 days. The
      enzymatic activity returned to its basal level after 14 days. The amylase values
      were normal in all the times evaluated in the control group. In optical
      microscopy, after the injection of L-arginine, a pancreatic architecture
      histologically preserved was observed after 6 hours, evidencing an important
      interstitial edema in 24 hours. After 48 hours, the acinar architecture was
      partially destroyed with focal cellular necrosis, reaching its maximum severity
      after 72 hours. On the 7th, the tissue necrosis and the edema had diminished, and
      the regeneration of the acinar architecture initiated. The pancreatic structural
      reconstruction could be observed after 14 days. Pancreatic histological changes
      were not found in the control group. CONCLUSION: - Experimental acute
      pancreatitis induced by L-arginine leads to pancreatic necrosis showing self
      limited evolution with pancreas regeneration in 2 weeks.

PMID- 15976913
TI  - [Microbiological evaluation of gastroscope decontamination by electrolysed acid
      water (Clentop WM-1)].
AB  - BACKGROUND: The manual disinfection of endoscopes with glutharaldeyde is widely
      employed. The great routine in gastroenteroscopy services, low number of
      equipment and the lack of technical knowledge about the decontamination processes
      are factors that stimulate the inadequate endoscope disinfection, intensifying
      the risk of transmission of microorganisms. The electrolysed acid water has been
      effective in the inactivation and destruction of microorganisms. AIM: The purpose
      of this investigation was to verify the microbicidal efficiency of electrolyzed
      acid water (Cleantop WM-1) to decontaminate gastroscopes after their using in
      patients. MATERIAL AND METHODS: Samples from biopsy channel of flexible
      endoscopes collected after patient use (n = 20) and after disinfection (n = 20)
      were cultivated in tryptic soy agar, MacConkey agar and Sabouraud dextrose agar.
      RESULTS: Seventeen of the 20 samples collected after patients examination yielded
      gram-negative bacilli, gram-positive coccus and yeast cells in contamination of 3
      to 5 log10 ufc/mL. Microbial growth was not verified in samples collected after
      the decontamination process. Conclusion - In this preliminary study, the
      mechanical disinfection carried through the Cleantop device with electrolyzed
      acid water showed satisfactory results for the elimination of microorganisms and
      time optimization in the reprocessing of gastroscopes.

PMID- 15976914
TI  - [Colon and rectal cancer mortality in Brazilian capitals, 1980-1997].
AB  - BACKGROUND: In Brazil, colorectal tumors are among the five more important sites
      of neoplasms, for both sexes, in terms of mortality. The etiology of colon and
      rectal cancer is complex and some of the factors involved in its genesis are
      related to diet. Brazilian geographic regions present heterogeneous alimentary
      profiles, that could be influencing the distribution of the mortality rates for
      these tumors. OBJECTIVE: To describe the patterns of mortality from cancers of
      the colon and the rectum in Brazilian State capitals in the period 1980-1997.
      MATERIAL AND METHODS: Mortality data for individuals of both sexes, residents in
      Brazilian State capitals (except Palmas, Tocantins) was obtained from the
      Ministry of Health Mortality System (SIM/MS). We considered as death from colon
      and rectum cancers those whose underlying cause of death was coded as 153.0 to
      153.9, 154.0 and 154.1, according to ICD 9, in the period 1980-95; C18.0 to
      C18.9, C19 and C20,according to ICD 10, in the period 1996-97. The trends of the
      standardized mortality rates from colon and rectum cancer were analyzed through
      linear regression models. RESULTS: The highest standardized mortality rates for
      colorectal cancer were observed in the South and Southeastern regions and varied
      between 8,0 and 10,7/100000 inhabitants. Porto Alegre (11,9), Sao Paulo (10,8)
      and Rio de Janeiro (9,6) presented the greatest rates among the State capitals in
      the study period. In the South region, rates of mortality for Porto Alegre and
      Florianopolis presented an increasing trend in the study period and the same
      behavior was observed for Sao Paulo and Vitoria in the Southeastern region.
      Brasilia and the other capitals of the Midwest, with the exception of Goiania,
      showed a tendency of increment of the mortality rates. Among the capitals of the
      North and Northeast regions, an increasing trend of mortality was observed in Rio
      Branco and Fortaleza. The separate analysis of the mortality rates for tumors of
      the colon and for tumors of the rectum showed a similar pattern, with higher
      values being observed for colon neoplasia. DISCUSSION: Regional differences in
      the mortality rates for colon and rectum neoplasias have been discussed for
      different authors, who point to the contribution of cultural and alimentary
      habits, and differences of life style and socioeconomic status to this
      heterogeneity, besides other aspects related to access to health services and
      quality of hospital care and preventive services. These factors must be
      considered in the evaluation of the differences observed in Brazilian capitals.
      Although the State capitals situated in South and Southeastern regions presented
      higher rates than the others, mortality rates of Porto Alegre (9,8/100.000) and
      Rio de Janeiro (9,0/100.000), in period 1983- 85, were about three times lower
      than those observed in the United States, Canada and France, in 1985. The sex
      distribution pattern of the mortality rates in Brazilian capitals was not
      uniform, with higher rates in men. We observed a trend of increment of the
      mortality rates of colorectal cancer in all Brazilian regions, similar to that
      was observed in some countries of the world, although with different gradients.
      CONCLUSIONS: The standardized mortality rates for colon and rectum neoplasias
      presented important regional differences among Brazilian State capitals. The
      highest rates were observed in the South and Southeastern regions. A trend of
      increment of the standardized mortality rates for cancers of the colon and the
      rectum was observed in all Brazilian regions in the period 1980-1997.

PMID- 15976915
TI  - A new Toll-road from environment to genes for rheumatic fever?

PMID- 15976916
TI  - Bmi1 in development and tumorigenesis of the central nervous system.
AB  - The role of the Polycomb group gene Bmi1 in proliferation control of lymphoid and
      neuronal progenitors as well as in self-renewal of haematopoietic and neural stem
      cells has been recently demonstrated. Here we review these recent findings with
      particular regard to their implications for central nervous system development
      and tumorigenesis.

PMID- 15976917
TI  - An oncolytic adenovirus controlled by a modified telomerase promoter is
      attenuated in telomerase-negative cells, but shows reduced activity in cancer
      cells.
AB  - The promoter for human telomerase reverse transcriptase (hTERTp) is
      preferentially active in malignant cells. It was recently used to control the
      expression of the adenoviral E1A gene for the development of oncolytic
      adenoviruses. To ensure maximal repression in normal cells, the inclusion of
      additional E-boxes in the proximal region of the core promoter was described. We
      found that the transcriptional activity of this artificial sequence (T-255-4DEB)
      is minimal in normal cells, but it is also reduced in all the cancer cell lines
      tested. The cancer specificity of a new oncolytic adenovirus based in this
      promoter (AdTE1) was evaluated by direct comparison with wild-type adenovirus
      type 5 (AdWT) in vitro and in vivo. In all the parameters tested, AdTE1 was
      attenuated in normal cells, but the efficacy in cancer cells showed a parallel
      reduction, suggesting a lack of specificity. However, the cytotoxicity of AdTE1
      was repressed in senescent cells compared to AdWT. Therefore, we conclude that
      AdTE1 is preferentially attenuated only in cells that are permanently devoid of
      telomerase expression such as senescent cells. Further modifications in the
      telomerase-based promoters should be introduced in order to combine maximal
      attenuation of oncolytic adenoviruses in normal tissues and enhanced activity in
      tumors.

PMID- 15976918
TI  - Transcriptome analysis of human hepatic and pancreatic stellate cells: organ
      specific variations of a common transcriptional phenotype.
AB  - Pancreatic stellate cells (PSCs) are thought to be the primary source of the
      extensive fibrotic reaction characteristic of pancreatic cancer and chronic
      pancreatitis in humans. PSCs share many morphological and functional
      characteristics with hepatic stellate cells (HSCs), whose central role in liver
      fibrosis is well established. However, it has remained unclear if hepatic and
      pancreatic stellate cells are derived from a common cell lineage and if they are
      completely similar or if they possess organ-specific features. We have analysed
      the transcriptomes of HSCs, PSCs and skin fibroblasts to assess how the
      transcriptional phenotype of stellate cells differs from that of a typical
      fibroblast lineage cell and if there is evidence for a common stellate cell
      precursor. To this end, we have performed expression profiling of primary
      cultures of human HSCs, PSCs and skin fibroblasts using 23,000-feature 'whole
      genome' oligonucleotide micro-arrays. Expression data were verified using real
      time PCR. The expression profiles of HSCs and PSCs displayed a great extent of
      similarity, clearly separating them from the fibroblasts. Predominantly
      extracellular and cell surface genes, but also signalling molecules,
      transcription factors and novel neural markers, were concordantly expressed in
      both stellate cell types. Despite this high degree of similarity, distinct
      differences in expression patterns were observed between HSCs and PSCs,
      reflecting organ-specific variations of the common stellate cell-specific
      phenotype.

PMID- 15976919
TI  - Intracellular S-adenosylhomocysteine increased levels are associated with DNA
      hypomethylation in HUVEC.
AB  - Hyperhomocysteinemia is a risk factor for atherosclerosis and vascular disease;
      however, the mechanism underlying this association remains poorly understood.
      Increased levels of intracellular S-adenosylhomocysteine (AdoHcy), secondary to
      homocysteine-mediated reversal of the AdoHcy hydrolase reaction, have been
      associated with reduced DNA methylation patterns and pointed as responsible for
      the hyperhomocysteinemia-related endothelial dysfunction. Methylation is an
      epigenetic feature of genomic DNA, which leads to alterations in gene expression.
      So far, the effect of intracellular AdoHcy accumulation on DNA methylation
      patterns has not yet been fully substantiated by experimental evidence. The
      present study was designed to evaluate, in cultured endothelial cells, the effect
      of AdoHcy accumulation on genomic global DNA methylation status. Experimental
      intracellular accumulation of AdoHcy was induced by adenosine-2,3-dialdehyde
      (ADA), an inhibitor of AdoHcy hydrolase. Increased concentrations of inhibitor
      were tested, and unsupplemented medium incubations were used as controls.
      Cytosolic and nuclear fractions were obtained from trypsinized cells after 72 h
      of incubation. Total homocysteine concentration was quantified (culture medium
      and cytosolic fractions) by high-performance liquid chromatography (HPLC). S
      Adenosylmethionine and AdoHcy concentrations were measured (cytosolic fractions)
      by stable-isotope dilution LC-tandem mass spectrometry method. Genomic DNA was
      obtained from the nuclear fraction, and global DNA methylation status was
      evaluated by the cytosine extension assay. The results showed that
      supplementation of the culture medium with ADA had no cytotoxic effect and
      increased the intracellular AdoHcy concentration in a dose-dependent manner. A
      significant negative correlation was observed between intracellular AdoHcy and
      genomic DNA methylation status. These findings strongly point to the importance
      of AdoHcy as a pivotal biomarker of genomic DNA methylation status.

PMID- 15976921
TI  - [Dissociative disorders].
AB  - There are problems with dissociative and conversion disorders with respect to
      classification, diagnosis, and therapeutic strategies which can only be
      understood in the historic context of hysteria. Even current diagnostic systems
      such as the DSM-IV and ICD-10 differ in the classification of such disorders.
      High prevalence rates ranging from 3% in the general population to 30% in
      clinical samples underscore their clinical relevance, and traumatic experiences
      play a major role in the pathogenesis. High rates of comorbid psychiatric
      disorders, the tendency to chronicity, and concepts of somatization (particularly
      in patients with conversion disorders) complicate psychotherapeutic approaches.
      Depending on the treatment goals, both psychodynamic and cognitive-behavioral
      methods can be applied, supplemented by specific techniques from trauma therapy,
      e.g. EMDR.

PMID- 15976920
TI  - Peroxisome proliferator-activated receptor-alpha and liver cancer: where do we
      stand?
AB  - The peroxisome proliferator-activated receptor-alpha (PPARalpha), first
      identified in 1990 as a member of the nuclear receptor superfamily, has a central
      role in the regulation of numerous target genes encoding proteins that modulate
      fatty acid transport and catabolism. PPARalpha is the molecular target for the
      widely prescribed lipid-lowering fibrate drugs and the diverse class of chemicals
      collectively referred to as peroxisome proliferators. The lipid-lowering function
      of PPARalpha occurs across a number of mammalian species, thus demonstrating the
      essential role of this nuclear receptor in lipid homeostasis. In contrast,
      prolonged administration of PPARalpha agonists causes hepatocarcinogenesis,
      specifically in rats and mice, indicating that PPARalpha also mediates this
      effect. There is no strong evidence that the low-affinity fibrate ligands are
      associated with cancer in humans, but it still remains a possibility that chronic
      activation with high-affinity ligands could be carcinogenic in humans. It is now
      established that the species difference between rodents and humans in response to
      peroxisome proliferators is due in part to PPARalpha. The cascade of molecular
      events leading to liver cancer in rodents involves hepatocyte proliferation and
      oxidative stress, but the PPARalpha target genes that mediate this response are
      unknown. This review focuses on the current understanding of the role of
      PPARalpha in hepatocarcinogenesis and identifies future research directions that
      should be taken to delineate the mechanisms underlying PPARalpha agonist-induced
      hepatocarcinogenesis.

PMID- 15976923
TI  - What the surgeon wins, and what the surgeon loses from intraoperative
      neurophysiologic monitoring?

PMID- 15976922
TI  - [Attention and executive functions in patients with severe obesity. A controlled
      study using the Attention Network Test].
AB  - In this paper, attention and temperament are compared between 41 severely obese
      patients with psychiatric comorbidity and 45 control persons. Networks of
      attention were assessed by the Attention Network Test: alerting (ability to
      achieve and maintain an alert state), orienting (ability to orient to a
      stimulus), and executive attention (ability to resolve conflict). According to
      hypotheses, obese patients show reduced executive attention, more effortful
      control, and higher negative affectivity than controls. The concept of attention
      networks is related to cognitive mechanisms of self-regulation, opening new
      perspectives for understanding psychiatric disorders.

PMID- 15976924
TI  - Mapping the binding site of full length HIV-1 Nef on human Lck SH3 by NMR
      spectroscopy.
AB  - The Nef protein of human immunodeficiency virus type 1 (HIV-1) is known to
      directly bind to the SH3 domain of human lymphocyte specific kinase (Lck) via a
      proline-rich region located in the amino terminal part of Nef. To address the
      question whether Nef binding to Lck SH3 involves residues outside the typical
      poly-proline peptide binding site and whether the Lck unique domain is involved
      in Nef-Lck interaction, we studied the direct interaction between both molecules
      using recombinant full-length HIV-1 Nef protein on one side and recombinantly
      expressed and uniformly 15N-isotope labeled Lck protein comprising unique and SH3
      domains on the other side. Applying nuclear magnetic resonance spectroscopy we
      could show that only residues of Lck SH3, that are typically involved in binding
      poly-proline peptides, are affected by Nef binding. Further, for the first time
      we could rule out that residues of Lck unique domain are involved in binding to
      full length Nef protein. Thus, interactions of Lck unique domain to cellular
      partners e.g. CD4 or CD8, are not necessarily competitive with Lck binding to HIV
      1 Nef.

PMID- 15976927
TI  - Prevention of peer rejection through a classroom-level intervention in middle
      school.
AB  - This project evaluated an intervention for preventing peer rejection in middle
      school that promoted social acceptance in the classroom environment. The systems
      level and preventive focus of this intervention differed markedly from
      traditional interventions that target putative deficits within individual
      rejected children. In collaboration with 24 teachers and their classrooms, the
      intervention team led mixed groups of accepted and rejected children in
      cooperative games that required teamwork and mutual respect among all members in
      order to succeed. To reinforce these alliances between children, as well as to
      prevent future peer rejection, teachers were encouraged to use cooperative,
      teamwork-based group activities for academic instruction. The intervention was
      evaluated using a randomized control (waitlist) design. Results suggested that
      the intervention reduced the amount of self-reported peer rejection in
      classrooms. Implications for the further development and evaluation of systems
      level interventions to prevent peer rejection are discussed. EDITORS' STRATEGIC
      IMPLICATIONS: The use of a systems-based prevention program shows promise for the
      prevention of children's perceived peer rejection. The authors demonstrate a
      model of university-community collaboration with a plan for sustainability and a
      focus on low-income and minority populations. Educators, school administrators,
      and researchers will be intrigued by the positive experiences of non-rejected
      peers and teachers in promoting a socially accepting school climate.

PMID- 15976928
TI  - How connectedness contributes to experimental smoking among rural youth:
      developmental and ecological analyses.
AB  - The influences of peer, sibling, and parents' smoking on adolescents' initiation
      of tobacco use have been explained as a function of peer pressure, genetics, and
      social learning processes, but rarely in combination or with assessments of the
      quality of these relationships. This study examined the additional contributions
      of connectedness to friends, siblings, parents, and teachers beyond the effects
      of friend, sibling, and parental smoking using logistic regression analyses with
      a cross-sectional middle and high school sample of 303 rural adolescents.
      Friends' and siblings' smoking, and connectedness to friends, were the strongest
      predictors of experimental smoking. Parental smoking and connectedness to parents
      and to teachers were significant predictors of experimental smoking when
      considered independently, but not after accounting for friend and sibling
      factors. Connectedness to parents and teachers decreased the odds of experimental
      smoking, while connectedness to friends increased the odds. EDITORS' STRATEGIC
      IMPLICATIONS: This strategy of assessing connectedness to-and smoking behaviors
      of-friends, siblings, teachers, and parents shows promise in predicting teens'
      cigarette smoking choices. The finding that the negative effects of
      unconventional connectedness and smoking by friends and siblings outweigh
      positive effects of connectedness to adults awaits replication with different
      samples and measures.

PMID- 15976929
TI  - Preventive psychology in primary care settings.
AB  - This article will describe some of the more promising types of preventive
      interventions that exist in primary health care settings. It will present a
      rationale for practicing psychologists to consider issues of prevention when
      working in health care settings. Approaches to prevention and the integration of
      preventive measures into primary care will be presented, as well as examples of
      the implementation of innovative prevention programs. This article will conclude
      with examples and recommendations for primary care psychologists who wish to
      become more involved with prevention. EDITORS' STRATEGIC IMPLICATIONS: The
      authors provide useful information and suggestions both for individual
      psychologists interested in focusing on individual-level interventions, as well
      as larger-scale interventions that present more challenges to implement, but also
      provide greater benefits to community health and well-being. Health care
      professionals and administrators could discern why and how to involve
      psychologists in their prevention efforts.

PMID- 15976930
TI  - Characteristics associated with differences in reported versus measured total
      cholesterol among male physicians.
AB  - We studied 4,543 male physicians to assess accuracy of self-reported cholesterol
      level. The rate of accurate reporting improved over 14 years (25% to 62%), while
      failing to report a cholesterol level decreased. Overweight, current or past
      smoking, and physical inactivity were significantly associated with not reporting
      or inaccurately reporting cholesterol level. Though an increasing proportion of
      physicians accurately reported their cholesterol level over time, those at
      increased risk for developing cardiovascular disease tended to underestimate or
      fail to report their cholesterol level. Knowledge may be a critical factor in
      empowering physicians and patients to advocate for and adopt healthier
      lifestyles. EDITORS' STRATEGIC IMPLICATIONS: Rates of sedentary behavior and
      obesity in the U.S. continue to rise. In this promising study with a large
      sample, a longitudinal design, and multi-method assessments, we find that--even
      among this sample of highly educated medical professionals--those individuals who
      are at greatest cardiovascular risk might require different types of monitoring,
      motivational interventions, or health education.

PMID- 15976931
TI  - Totally extraperitoneal laparoscopic hernia repair in patients with previous
      lower abdominal surgery.
AB  - INTRODUCTION: Patients with lower abdominal scars are generally excluded from
      laparoscopic hernia repair due to the perceived technical difficulty and risk of
      visceral injury. This study examines the outcome of a series of patients who
      underwent totally extraperitoneal (TEP) inguinal hernia repair despite previous
      lower abdominal surgery. METHODS: Retrospective review of 47 consecutive patients
      who underwent TEP inguinal hernia repair in the presence of lower abdominal scars
      between 1993 and 2002. RESULTS: Thirty-five unilateral and 12 bilateral TEP
      hernia repairs were performed in the presence of 20 appendicectomy, 10 lower
      midline, 18 suprapubic and 5 paramedian incisions. Two cases were converted to
      open repair. There were no major complications and no early or late recurrences.
      Median operating time was 67.5 min and 83% of patients were managed as day cases.
      CONCLUSIONS: Totally extraperitoneal laparoscopic hernia repair can be carried
      out safely in the presence of scars from previous lower abdominal surgery.

PMID- 15976933
TI  - Phylogenetic analysis of six species of pacific abalone (Haliotidae) based on DNA
      sequences of 16s rRNA and cytochrome c oxidase subunit I mitochondrial genes.
AB  - Six species of abalones (Haliotidae) are found on the Korean coasts.
      Identification and characterization of these abalones are usually based on
      morphologic characters. In this research we compared the partial sequences of the
      mitochondrial 16S ribosomal RNA and cytochrome c oxidase subunit I genes to
      identify species using molecular data and to determine their phylogenetic
      relationships. Sequence alignments and phylogenetic analysis revealed that the 6
      species fell into 2 distinct groups which were genetically distant from each
      other and exhibited little internal phylogenetic resolution. One group included
      Haliotis discus hannai, H. discus discus, H. madaka, and H. gigantea, while the
      other group contained H. diversicolor supertexta and H. diversicolor
      diversicolor. The 16S rRNA sequences were relatively more conserved than to the
      COI sequences, but both gene sequences provided sufficient phylogenetic
      information to distinguish among the 6 species of Pacific abalone, and thus could
      be valuable molecular characters for species identification.

PMID- 15976934
TI  - Shark (Scyliorhinus torazame) metallothionein: cDNA cloning, genomic sequence,
      and expression analysis.
AB  - Novel metallothionein (MT) complementary DNA and genomic sequences were isolated
      from a cartilaginous shark species, Scyliorhinus torazame. The full-length open
      reading frame (ORF) of shark MT cDNA encoded 68 amino acids with a high cysteine
      content (29%). The genomic ORF sequence (932 bp) of shark MT isolated by
      polymerase chain reaction (PCR) comprised 3 exons with 2 interventing introns.
      Shark MT sequence shared many conserved features with other vertebrate MTs:
      overall amino acid identities of shark MT ranged from 47% to 57% with fish MTs,
      and 41% to 62% with mammalian MTs. However, in addition to these conserved
      characteristics, shark MT sequence exhibited some unique characteristics. It
      contained 4 extra amino acids (Lys-Ala-Gly-Arg) at the end of the beta-domain,
      which have not been reported in any other vertebrate MTs. The last amino acid
      residue at the C-terminus was Ser, which also has not been reported in fish and
      mammalian MTs. The MT messenger RNA levels in shark liver and kidney, assessed by
      semiquantitative reverse transcriptase PCR and RNA blot hybridization, were
      significantly affected by experimental exposures to heavy metals (cadmium,
      copper, and zinc). Generally, the transcriptional activation of shark MT gene was
      dependent on the dose (0-10 mg/kg body weight for injection and 0-20 microM for
      immersion) and duration (1-10 days); zinc was a more potent inducer than copper
      and cadmium.

PMID- 15976935
TI  - Gene expression in Florida red tide dinoflagellate Karenia brevis: analysis of an
      expressed sequence tag library and development of DNA microarray.
AB  - Karenia brevis (Davis) is the dinoflagellate responsible for nearly annual red
      tides in the Gulf of Mexico. Although the mechanisms regulating the growth and
      toxicity of this problematic organism are of considerable interest, little
      information is available on its molecular biology. We therefore constructed a
      complementary DNA library from which to gain insight into its expressed genome
      and to develop tools for studying its gene expression. Large-scale sequencing
      yielded 7001 high-quality expressed sequence tags (ESTs), which clustered into
      5280 unique gene groups. The vast majority of genes expressed fell into a low
      abundance class, with the highest expressed gene accounting for only 1% of the
      total ESTs. Approximately 29% of genes were found to have similarity to known
      sequences in other organisms after BLAST similarity comparisons to the GenBank
      public protein database using a cutoff of P < 10e(-4). We identified for the
      first time in a dinoflagellate a suite of conserved eukaryotic genes involved in
      cell cycle control, intracellular signaling, and the transcription and
      translation machinery. At least 40% of gene clusters displayed single nucleotide
      polymorphisms, suggesting the presence of multiple gene copies. The average GC
      content of ESTs was 51%, with a slight preference for G or C in the third codon
      position (53.5%). The ESTs were used to develop an oligonucleotide microarray
      containing 4629 unique features and 3462 replicate probes. Microarray labeling
      has been optimized, and the microarray has been validated for probe specificity
      and reproducibility. This is the first information to be developed on the
      expressed genome of K. brevis and provides the basis from which to begin
      functional genomic studies on this harmful algal bloom species.

PMID- 15976936
TI  - Rapid PCR-RFLP method for discrimination of imported and domestic mackerel.
AB  - With the ever-decreasing domestic fishery catch of Japanese mackerel Scomber
      japonicus, alternative Atlantic mackerel Scomber scombrus has been increasingly
      imported and currently accounts for approximately 34% of mackerel consumption in
      Japan. As there is no morphologic difference between the species after removal of
      their skin, not only fresh and frozen fillets but also processed seafood of S.
      scombrus are frequently marketed with mislabeling as S. japonicus. In this study,
      a rapid and reliable polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis was developed to discriminate imported mackerel
      S. scombrus and domestic mackerel S. japonicus. PCR amplification for the nuclear
      5S ribosomal DNA nontranscribed spacer was performed using Scomber-specific
      primers. Direct digestions of the PCR products using either PvuII or HaeIII
      restriction enzymes generated species-specific profiles, indicating that both
      enzymes enable the accurate identification of S. scombrus and S. japonicus. This
      robust and reproducible method can serve as molecular-based routine food
      inspection program to enforce labeling regulations.

PMID- 15976937
TI  - Molecular biomarkers and adaptation to environmental stress in moon jelly
      (Aurelia spp.).
AB  - We describe a strategy that identifies molecular biomarkers and links the study
      of abiotic stress to evolutionary history. By utilizing the moon jellyfish
      Aurelia spp. as a model, we identified genes differentially regulated in response
      to the chemical stressor tributyltin by means of complementary DNA subtraction
      analyses. Expression of 3 out of 25 identified candidate genes, one oxidative
      stress gene, one heat shock (hsp70) gene, and one GTP-binding gene, was
      quantified under laboratory conditions and in field tests using semiquantitative
      reverse transcriptase polymerase chain reaction. Differential expression patterns
      were found following exposure to tributyltin and temperature treatments. The
      findings suggest that the identified genes are involved in response to chemical
      as well as heat- induced stress and may serve as biomarkers for monitoring marine
      habitats. Gene regulatory patterns combined with phylogenetic inferences of the
      hsp70 gene support a possible role of ecologically driven divergence within the
      genus Aurelia. We show that added information on genetic variability can raise
      the predictive power of molecular biomarkers in studies of individual stress
      response.

PMID- 15976938
TI  - The piscine SAF-1 cell line: genetic stability and labeling.
AB  - Fish cell lines are increasingly important research tools. The SAF-1 cell line,
      fibroblast-like culture derived from the marine fish gilthead seabream (Sparus
      aurata), has proved useful in many applications, especially in viral research.
      For cell lines intended as in vitro models, characterization of their properties
      and authentication are essential for deeper understanding of their performance
      and thus more precise experimental design and applicability. In this study we
      characterized the SAF-1 cell line in terms of genetic stability through time and
      genetic labeling. Methods for determining stability include telomerase activity,
      karyotyping, mapping of ribosomal RNA regions, and DNA content. For genetic
      labeling 12 microsatellite loci were used. The results indicate that telomerase
      has been activated in the course of SAF-1 development, and the highest levels of
      telomerase activity correlate with an increase in cell proliferation, thus
      supporting a permanent cell line. This stability is in agreement with the normal
      situation presented by the cytogenetic traits and DNA content values, and the
      genotypic profile allows SAF-1 authentication at the single individual level.
      This study increases the value of SAF-1 as an in vitro system, which is now one
      of the few well-characterized cell lines from a marine fish.

PMID- 15976939
TI  - Assignment of sockeye salmon (Oncorhynchus nerka) to spawning sites using DNA
      markers.
AB  - Randomly amplified polymorphic DNA (RAPD) markers were used to assign individual
      adult sockeye salmon to their spawning sites using a genotype assignment test.
      Six primers were selected for use by screening bulked DNA samples for markers
      missing in fish from one or more of 5 sites in British Columbia or Alaska. Of 73
      markers scored, 54 showed variation between or within sites among the sampled
      fish. Thirty-seven of the variable markers were not detected in any fish from one
      or more sites; 18 variable markers were detected in all fish from one or more
      other sites. Thus 25% of markers scored were found in all fish of some sites and
      in no fish of some other sites. An assignment test placed all 70 fish tested into
      their correct populations. Principal coordinate analysis of genetic variation
      produced clusters of fish corresponding to each sampling site. No sex-specific
      RAPD markers were detected among more than 1300 screened.

PMID- 15976940
TI  - The hypervariable domain of the mitochondrial control region in Atlantic spiny
      lobsters and its potential as a marker for investigating phylogeographic
      structuring.
AB  - Atlantic spiny lobsters support major fisheries in northeastern Brazilian waters
      and in the Caribbean Sea. To avoid reduction in diversity and elimination of
      distinct stocks, understanding their population dynamics, including structuring
      of populations and genetic diversity, is critical. We here explore the potential
      of using the hypervariable domain in the control region of the mitochondrial DNA
      as a genetic marker to characterize population subdivision in spiny lobsters,
      using Panulirus argus as the species model. The primers designed on the
      neighboring conserved genes have amplified the entire control region (approx. 780
      bases) of P. argus and other closely related species. Average nucleotide and
      haplotype diversity within P. argus were found to be high, and population
      structuring was hypothesized. The data suggest a division of P. argus into
      genetically different phylogeographic groups. The hypervariable domain seems to
      be useful for determining genetic differentiation of geographically distinct
      stocks of P. argus and other Atlantic spiny lobsters.

PMID- 15976941
TI  - Optimization of omega-3 fatty acid production by microalgae: crossover effects of
      CO2 and light intensity under batch and continuous cultivation modes.
AB  - The microalga Pavlova lutheri is a potential source of economically valuable
      docosahexaenoic and eicosapentaenoic acids. Specific chemical and physical
      culture conditions may enhance their biochemical synthesis. There are studies
      relating the effect of CO2 on growth; however, this parameter should not be
      assessed independently, as its effect strongly depends on the light intensity
      available. In this research, the combined effects of light intensity and CO2
      content on growth and fatty acid profile in P. lutheri were ascertained, in order
      to optimize polyunsaturated fatty acid production. The influence of the operation
      mode was also tested via growing the cultures by batch and by continuous
      cultivation. Higher light intensities associated with lower dilution rates
      promoted increases in both cell population and weight per cell. Increased levels
      of CO2 favored the total lipid content, but decreased the amounts of
      polyunsaturated fatty acids. Mass productivities of eicosapentaenoic acid (3.61
      +/- 0.04 mg . L(-1) . d(-1)) and docosahexaenoic acid (1.29 +/- 0.01 mg . L(-1) .
      d(-1)) were obtained in cultures supplied with 0.5% (v/v) CO2, at a dilution rate
      of 0.297 d(-1) and a light intensity of 120 muE . m(-2) . s(-1).

PMID- 15976942
TI  - Novel sulfated polysaccharide derived from red-tide microalga Gyrodinium
      impudicum strain KG03 with immunostimulating activity in vivo.
AB  - The high-sulfate-containing exopolysaccharide p-KG03 is produced by the red-tide
      microalga Gyrodinium impudicum strain KG03. The immunostimulatory effects of this
      sulfated exopolysaccharide were investigated by isolating peritoneal macrophages
      from mice 10 or 20 days after they had received a single dose of p-KG03 (100 or
      200 mg/kg body weight). The cytotoxicity of the isolated macrophages for B16
      tumor cells was tested, as B16 tumor cells are sensitive to tumor necrosis factor
      alpha (TNF-alpha) and nitric oxide. The activities of natural killer cells from
      the p-KG03-treated mice against YAC-1 mouse lymphoma cells were also tested. The
      nonspecific immune functions mediated by natural killer cells and macrophages
      were increased by treatment with p-KG03 in vivo. These results suggest that p
      KG03 has immunostimulatory effects and enhances the tumoricidal activities of
      macrophages and NK cells in vivo. In addition, p-KG03 treatment increased the
      plaque-forming cell response to sheep red blood cells, as well as the levels of
      IgM and IgG Exposure to p-KG03 also increased the production by macrophages of
      cytokines, such as interleukins -1beta and -6, and TNF-alpha. This is the first
      report of a marine microalgal sulfated polysaccharide having immunostimulatory
      activities. The p-KG03 polysaccharide may be useful for the development of
      biotechnological and pharmaceutical products that incorporate bioactive marine
      exopolysaccharides.

PMID- 15976943
TI  - Proteomic approach to probe for larval proteins of the mussel Mytilus
      galloprovincialis.
AB  - A proteomic approach was used to search for larval proteins specific to the
      mussel Mytilus galloprovincialis from Galicia in northwest Spain. The study
      included both a comparative analysis, through two-dimensional electrophoresis, of
      protein expression maps of the larvae of the mussel and of 5 abundant and
      commercially important bivalve species from the region (Ostrea edulis,
      Cerastoderma edule, Pecten maximus, Tapes decussatus, and Venarupis pullastra)
      and subsequent mass spectrometric analysis of some of the protein spots. A total
      of 18 spots were selected and isolated from gels of M. galloprovincialis larvae.
      From their relative position on the electrophoresis gels, 6 of these were clearly
      exclusive to the mussel species. However, it was not clear whether the other
      spots were shared by other species. To overcome this ambiguity, first an analysis
      using matrix assisted laser desorption ionization with time-of-flight (MALDI-TOF)
      was conducted on the 6 spots of Mytilus that could possibly be shared with only
      one species. The peptide mass fingerprinting was completely different for the
      proteins compared. This result confirmed that the 6 proteins were exclusively
      mussel proteins, but demonstrated the utility of this approach when working with
      species that are poorly represented at the protein level in databases.

PMID- 15976944
TI  - Liver metastasis and ICAM-1 mRNA expression in the liver after carbon dioxide
      pneumoperitoneum in a murine model.
AB  - BACKGROUND: Liver metastasis of colorectal malignancies is an important
      prognostic factor. Several studies have demonstrated that carbon dioxide (CO2)
      pneumoperitoneum enhances liver metastasis in animal models. Little is known
      about intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha
      (TNF-(alpha) mRNA expression in the liver after CO2 pneumoperitoneum. METHODS:
      Forty-five male BALB/c mice were randomly divided into three groups after intra
      splenic tumor cell (colon 26) inoculation and the following procedures were
      performed: CO2 pneumoperitoneum (n = 15), open laparotomy (n = 15), and
      anesthesia alone (n = 15). On day 7 after each procedure, the livers were excised
      and the number and diameter of the tumor nodules and the cancer index score were
      determined. Another 90 male BALB/c mice were randomly divided into three groups
      as described above, and they underwent each procedure (n = 30 each). After each
      procedure, the livers were excised on days 0, 1, 3, and ICAM-1 and TNF-alpha mRNA
      expression were examined by real-time RT-PCR using SYBR Green I. RESULTS: The
      number of tumor nodules and the cancer index score were larger in the CO2
      pneumoperitoneum group than in the control group (p < 0.05). The mean diameter of
      the tumor nodules was not different among the three groups. The expression of
      ICAM-1 in the CO2 pneumoperitoneum group was higher than that in the other groups
      on day 1 (p < 0.05), and the TNF-alpha mRNA was higher than that in the control
      group on day 1 (p < 0.05). CONCLUSIONS: CO2 pneumoperitoneum enhances liver
      metastasis compared with anesthesia alone, and ICAM-1 expression in the liver
      after the pneumoperitoneum plays an important role in establishing liver
      metastasis in a murine model.

PMID- 15976945
TI  - Development and perspectives of perfusion treatment for liver failure.
AB  - To treat patients with severe liver failure, liver transplantation and blood
      purification therapy, including plasmapheresis, hemodiafiltration, and
      bioartificial liver support, are available. The two mainstream systems developed
      for bioartificial liver support are extracorporeal whole liver perfusion (ECLP)
      and the bioreactor system (BIS). We developed a method of cross-plasma perfusion,
      in which plasma is exchanged between the blood circuit of the patient and that of
      a hepatic functioning unit, through which immunologically free whole human blood
      is perfused. From the aspects of efficacy and epidemic safety, the best system of
      bioartificial liver support for clinical use is considered to be ECLP in cross
      plasma perfusion. In opposition, a social antagonist for zoonosis has
      consistently been raised, with controversy surrounding the use of xenogeneic
      organs for human treatment, which might be final obstacle. It is possible that
      the combination therapy of hemodiafiltration and the administration of human
      serum albumin and anticoagulant factors, which minimizes the economic and medical
      resource costs through the development of transgenic livestock that secrete human
      pharmaceuticals systemically, will become a more desirable and practical
      treatment for patients with severe liver failure.

PMID- 15976946
TI  - Nonoperative management of tracheobronchial injuries in severely injured
      patients.
AB  - PURPOSE: A rupture of the airway due to blunt chest trauma is rare, and treatment
      can prove challenging. Many surgeons suggest operative management for these kinds
      of injuries. Nonoperative therapy is reported only in exceptional cases. But
      there is still a lack of evidence from which to recommend surgical repair of
      these injuries as the first choice procedure. METHODS: We retrospectively
      analyzed the records of 92 multiple injured patients admitted to our trauma
      department between July 2002 and July 2003 for the incidence and management of
      tracheobronchial rupture (TBR). RESULTS: Five (5.4%) of 92 patients suffered from
      tracheobronchial injuries. The mean injury severity score was 38. There were
      three male and two female patients, with a mean age of 23 years. All patients had
      lesions <2 cm in size and were treated nonoperatively. One patient died from
      multiorgan failure, but the others recovered from TBR uneventfully. One patient
      developed acute pneumonia as a result of respirator therapy, but none of the
      patients had mediastinitis or tracheal stenosis within 3 months after injury.
      CONCLUSION: We believe that surgical treatment is not mandatory in patients with
      small to moderate ruptures, and such aggressive treatment may even have adverse
      effects, especially in patients with multiple injuries.

PMID- 15976947
TI  - Matrix metalloproteinase-9 expression in congenital diaphragmatic hernia during
      mechanical ventilation.
AB  - PURPOSE: Matrix metalloproteinase-9 (MMP-9) is detected in lung tissues subjected
      to ventilator-induced injury and is involved in the process of lung injury. We
      investigated the immunohistochemical expression of MMP-9 in the bilateral lungs
      of newborns with congenital diaphragmatic hernia (CDH) during mechanical
      ventilation and evaluated the degree of damage based on MMP-9 expression.
      METHODS: Lung tissue samples were obtained during autopsy from six newborns with
      CDH. Control lung tissue samples were obtained from two of these newborns; one
      who died of persistent pulmonary hypertension after being ventilated for 2 days,
      but whose bilateral lungs were not subjected to the compressions of herniation,
      and one who died of bilateral diaphragmatic hernias soon after birth, but was not
      subjected to artificial ventilation. The other four newborns with CDH had
      unilateral Bochdalek hernias. Immunohistochemical detection of MMP-9 expression
      was done using a wet autoclave antigen retrieval method on sections from formalin
      fixed and paraffin-embedded lung tissue. RESULTS: The reaction and distribution
      of MMP-9 was strongly positive in the alveolar macrophages in thickened alveolar
      septi and ducts, and in the inflammatory cells around the parenchymal hemorrhage
      and intra-alveolar spaces. Only the four patients with unilateral Bochdalek
      hernia had widely positive MMP-9 immunoreactivity in the unaffected side, as well
      as the affected side. CONCLUSIONS: Based on MMP-9 expression, the lungs of
      newborns with CDH were damaged bilaterally during mechanical ventilation.

PMID- 15976948
TI  - Analysis of the factors related to a decrease in jugular venous oxygen saturation
      in patients with diabetes mellitus during normothermic cardiopulmonary bypass.
AB  - PURPOSE: We sought to examine what factors, including cerebrovascular carbon
      dioxide (CO(2)) reactivity, are related to a decrease in internal jugular venous
      oxygen saturation (SjvO(2)) during normothermic cardiopulmonary bypass (CPB) in
      patients with diabetes mellitus. METHODS: Twenty-three diabetic patients
      scheduled to undergo elective coronary artery bypass grafting were studied. As a
      control, 27 age-matched control patients without diabetes mellitus were also
      examined. After the induction of anesthesia, a fiberoptic oximetry oxygen
      saturation catheter was inserted into the right jugular bulb to continuously
      monitor SjvO(2). Arterial and jugular venous blood gases were measured during
      CPB. The cerebrovascular CO(2) reactivity was measured after the induction of
      anesthesia and before the start of surgery using a 2.5-MHz pulsed transcranial
      Doppler probe. RESULTS: The SjvO(2) values in the diabetic group were lower than
      those in the control group at the initiation of CPB and at 20, 40, and 60 min
      after the start of CPB. The values for pre- and post-CO(2) reactivity in the
      control group did not significantly differ (pre-CPB: 4.8% +/- 2.3% mmHg(-1); post
      CPB: 5.9% +/- 4.4% mmHg(-1)). In contrast, the values for CO(2) reactivity were
      lower post CPB than pre-CPB in the diabetic group (Pre-CPB: 6.3% +/- 2.9% mmHg(
      1); post-CPB: 4.7% +/- 2.6% mmHg(-1); P < 0.05). In the diabetic group,
      glycosylated hemoglobin A1c (HbA1c) is considered to be a factor related to a
      decrease in SjvO(2) during CPB. CONCLUSIONS: Cerebrovascular CO(2) reactivity in
      diabetic patients decreased after the cessation of CPB but not in the control
      patients. In addition, HbA1c is also thought to be a factor related to a decrease
      in SjvO(2) in diabetic patients.

PMID- 15976949
TI  - Reliability and validity of a new scale to assess postoperative dysfunction after
      resection of upper gastrointestinal carcinoma.
AB  - PURPOSE: We evaluated the purpose reliability and validity of a preliminary
      scale, which we developed to assess postoperative dysfunction after surgery for
      gastric and esophageal carcinoma. METHODS: After interviews with 12 patients,
      reviews of previous studies, and discussions with experts, we identified the
      physical symptoms that develop after resection of upper gastrointestinal (GIT)
      carcinoma, and devised a preliminary scale comprised of 34 items. A questionnaire
      survey based on this scale was then sent to 283 patients. RESULTS: The
      questionnaire was returned by 223 patients (78.8%), and 219 responses (98.2%)
      were valid. Among the 219 respondents, 168 had gastric carcinoma and 51 had
      esophageal carcinoma. After the elimination of scale items regarded as irrelevant
      based on statistical considerations and the judgment of experts, factor analysis
      was done. Seven factors were valid, namely, limited activity due to decreased
      food consumption, reflux, gastric dumping, nausea and vomiting, deglutition
      difficulty, pain, and difficulty with passing stools, which were often poorly
      formed. Scale reliability was confirmed by a Cronbach alpha-coefficient of 0.924.
      The validity of the construction of this scale was confirmed using the known
      group technique based on the operative procedures performed, and the results of
      factorial validity. CONCLUSION: Our preliminary scale is sufficiently reliable
      and valid, and will prove to be clinically useful.

PMID- 15976950
TI  - Hepatic artery pseudoaneurysm: a report of seven cases and a review of the
      literature.
AB  - PURPOSE: To analyze seven cases of hepatic artery pseudoaneurysm (HAP)
      encountered at our hospital and review the relevant literature. METHODS: We
      searched the computerized medical record database from January 1, 1996, to
      September 1, 2003, to identify all cases of HAP, which we then reviewed in
      detail, examining etiology, findings, laboratory data, therapeutic intervention,
      complications, and outcome. We then compared these findings with those reported
      in the literature. RESULTS: There were five cases of HAP among 18,015 trauma and
      surgical admissions to the University of California Irvine Medical Center,
      representing an incidence of 0.03%. There were an additional two cases of HAP
      among 200 orthotopic liver transplants (OLT). The five HAPs not associated with
      OLT were preceded by blunt abdominal trauma, liver biopsy, pancreatic pseudocyst,
      and polyarteritis nodosa, in one patient each, and there was no apparent cause in
      one patient. Two patients were treated by ligation, and the patients with post
      OLT HAP underwent resection and replacement with saphenous bypass grafts.
      Successful embolization was performed in the other three patients. CONCLUSION:
      Hepatic artery pseudoaneurysm is a rare but dangerous complication of both acute
      surgical and chronic injury to the hepatic artery. However, early diagnosis and
      intervention can result in an excellent long-term outcome.

PMID- 15976952
TI  - Early versus delayed cholecystectomy for acute cholecystitis: a meta-analysis of
      randomized controlled trials.
AB  - PURPOSE: We performed a meta-analysis of randomized controlled trials to
      determine the optimal timing of laparoscopic cholecystectomy and open
      cholecystectomy for acute cholecystitis. METHODS: We retrieved randomized
      controlled trials (RCTs) that compared early with delayed cholecystectomy for
      acute cholecystitis by systematically searching Medline and the Cochrane Library
      for studies published between 1966 and 2003. The outcomes of primary interest
      were mortality and morbidity. RESULTS: The ten trials we analyzed comprised 1 014
      subjects; 534 were assigned to the early group and 480 assigned to the delayed
      group. The combined risk difference of mortality appeared to favor open
      cholecystectomy in the early period (risk difference, -0.02; 95% confidence
      interval, -0.44 to -0.00), but no differences were found among laparoscopic
      procedures or among all procedures. The combined risk difference of morbidity
      showed no differences between the open and laparoscopic procedures. The combined
      risk difference of the rate of conversion to open surgery showed no differences
      in the included laparoscopic studies; however, the combined total hospital stay
      was significantly shorter in the early group than in the delayed group.
      CONCLUSIONS: There is no advantage to delaying cholecystectomy for acute
      cholecystitis on the basis of outcomes in mortality, morbidity, rate of
      conversion to open surgery, and mean hospital stay. Thus, early cholecystectomy
      should be performed for patients with acute cholecystitis.

PMID- 15976951
TI  - Effectiveness of radiation therapy after surgery for hilar cholangiocarcinoma.
AB  - PURPOSE: Some studies suggest that giving radiation therapy after surgery for
      hilar cholangiocarcinoma improves the survival rate; however, many of these
      studies did not specify numbers of subjects or provide an impartial analysis.
      Thus, we evaluated the effectiveness of radiation therapy as adjuvant treatment
      after surgery and attempted to establish appropriate adaptation standards.
      METHODS: We reviewed the records of 69 patients who underwent surgery for hilar
      cholangiocarcinoma between June 1980 and April 1998. Thirty-nine patients were
      treated with surgery followed by radiation therapy and 30 were treated with
      surgery alone. RESULTS: The clinicopathologic features that might have influenced
      prognosis were similar in the patients who received radiation therapy and those
      who did not. Radiation as adjuvant therapy did not have a beneficial effect on
      overall survival (P = 0.554, log-rank test); however, it tended to improve
      survival in the group of patients who underwent curative resection for with p
      stage III or IVa disease (P = 0.042, log-rank test). CONCLUSIONS: Radiation
      therapy after surgery did not show any clinical benefits for patients with hilar
      cholangiocarcinoma. However, it may be effective as adjuvant therapy after
      curative resection in a small subgroup of patients with p-stage III or IVa
      disease.

PMID- 15976953
TI  - Traumatic injuries to the subclavian and axillary arteries: a 13-year review.
AB  - PURPOSE: By reviewing our experience, we evaluated the presentation, management,
      and long-term outcome of patients with subclavian and axillary artery injuries
      resulting from trauma. METHODS: We retrospectively reviewed the data of 38
      patients who received treatment for subclavian or axillary artery injuries in the
      Emergency and Trauma Department of Medical Faculty of Istanbul, Istanbul
      University between January 1989 and July 2002. RESULTS: Arterial injuries were
      repaired with an end-to-end anastomosis in 10 (26.3%) patients, primary repair in
      6 (15.7%), autologous vein graft interposition in 16 (42%), ligation in 5
      (13.1%), and a proximal subclavian-brachial artery bypass in 1 (2.6%). One (2.6%)
      of the arterial reconstructions failed in the perioperative period. Fourteen
      (36%) patients presented with a neurological deficit, which recovered after the
      intervention in 2 (5.2%) patients. A wound infection developed in 8 (21%)
      patients and 2 (5.2%) patients died of concomitant injuries. Thirteen (36.1%) of
      the remaining 36 patients were followed up for a mean period of 7 months.
      CONCLUSION: Successful management of subclavian and axillary artery injuries
      requires prompt diagnosis because the occult nature of these injuries
      necessitates a high index of suspicion. Although revascularization procedures are
      often successful, it is the associated neurological, orthopedic, and soft tissue
      injuries that affect the functional outcome of the limb.

PMID- 15976954
TI  - A new, simple stapling technique for pulmonary emphysema: its effects and safety
      for improving respiratory function.
AB  - PURPOSE: We performed lung volume reduction surgery (LVRS) in an experimental
      model using a simple stapling technique (SST) for pulmonary emphysema. The
      technique uses a stapler to isolate the affected lung from the remaining lung
      instead of removing it. We performed the present experiment using dogs to study
      the effects and safety of LVRS using the SST. METHODS: Pulmonary emphysema was
      induced in 12 dogs with papain. They were divided into three groups: those
      operated on with SST composed the operation (Op) group; those receiving an
      experimental thoracotomy composed the sham-operation (Sham-op) group; and those
      not operated on composed the nonoperation (Non-op) group. Respiratory function
      was compared among the groups before induction of emphysema (baseline), after
      induction of emphysema (preoperation), and at 8 weeks after the operation
      (postoperation Op and Sham-op groups only). The lung was removed and
      histologically examined 8 weeks after the SST operation. RESULTS: In the Op
      group, alteration in forced expiratory volume (FEV) 0.5%, airway resistance (Raw)
      and specific airway conductance (sGaw) showed significantly favorable results.
      Histologically, the isolated area was widely replaced by fibrous tissue with
      numerous blood vessels in the circumference in the Op group; no signs of
      infection such as polykaryoleukocytes or microabscesses were observed in any of
      the samples. CONCLUSION: The LVRS for pulmonary emphysema using a simple stapling
      technique improved the expiratory flow and alleviated airway resistance. The
      isolated remaining lung was well organized without any infectious events or
      secondary adversity, thus demonstrating the safety of this technique. From these
      results, this technique is therefore suggested to be effective and applicable to
      clinical use.

PMID- 15976956
TI  - Reoperations after failure of stent grafting for type B aortic dissection: report
      of two cases.
AB  - We describe our successful management of two patients who suffered complications
      after stent grafting for Type B aortic dissections. One patient was found to have
      stent-graft migration, which we treated with repeat aortic stent grafting, and
      the other patient had a proximal endoleak and total occlusion of the stent graft,
      which we treated with open surgical repair. We discuss the measures used to
      assist us in deciding on the most appropriate surgery, as well as the treatment
      alternatives.

PMID- 15976955
TI  - Protective effect of MESNA (2-mercaptoethane sulfonate) against hepatic
      ischemia/reperfusion injury in rats.
AB  - PURPOSE: Reoxygenation of ischemic tissue generates various reactive oxygen
      metabolites (ROMs), which have a deleterious effect on various cellular
      functions. We evaluated the possible protective effect of 2-mercaptoethane
      sulfonate (MESNA) on hepatic ischemia/reperfusion (I/R) injury. METHODS: Wistar
      albino rats were subjected to 45-min hepatic ischemia, followed by 60-min
      reperfusion. 2-Mercaptoethane sulfonate, 150 mg/kg, or saline was given
      intraperitoneally (i.p.) twice, 15 min before ischemia and immediately before
      reperfusioin. We measured serum aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) levels to assess liver function. Liver tissue samples were
      taken to measure the levels of malondialdehyde (MDA), an end-product of lipid
      peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO)
      activity, as an indirect index of neutrophil infiltration. We also measured
      hepatic collagen content, as a fibrosis marker. RESULTS: Plasma ALT and AST
      levels were higher in the I/R group than in the control group, but this increase
      was significantly decreased by MESNA treatment. Hepatic GSH levels, which were
      significantly depressed by I/R, increased back to the control levels in the MESNA
      treated I/R group. Increases in tissue MDA levels and MPO activity caused by I/R
      injury decreased back to the control levels after MESNA treatment. Similarly, the
      increased hepatic collagen content in the I/R group decreased to the level of the
      control group after MESNA treatment. CONCLUSION: The fact that MESNA alleviated
      I/R-induced injury of the liver and improved hepatic structure and function
      suggests that its antioxidant and oxidant scavenging properties may be of
      therapeutic value in protecting the liver against oxidative injury caused by I/R.

PMID- 15976957
TI  - Successful resection of an infected duodenal duplication cyst after percutaneous
      cyst drainage: report of a case.
AB  - We report a case of a duodenal duplication cyst complicated by infection. An 8
      year-old boy was brought to our hospital with severe abdominal pain and a fever
      of 39.8 degrees C. He had a 5-year history of occasional abdominal pain with
      vomiting. On examination, a cystic mass was felt under the liver. We performed
      percutaneous drainage of the cyst under a suspected diagnosis of a choledochal
      cyst complicated by acute biliary infection. A contrast study through the
      drainage tube and surgical exploration revealed a duodenal duplication cyst
      communicating with the second part of the duodenum. The patient had an uneventful
      recovery and remains well 5 years after surgery. To the best of our knowledge,
      this is the first documented case of an infected duodenal duplication cyst
      successfully treated by resection after percutaneous drainage.

PMID- 15976958
TI  - Granulocyte-colony stimulating factor-producing gallbladder cancer without
      recurrence more than 2 years after resection: report of a case.
AB  - Patients with gallbladder carcinoma rarely have remarkable granulocytosis.
      Although surgical resection is the most effective treatment, patients with
      gallbladder carcinoma generally have a very poor prognosis. We report a case of a
      rapidly growing gallbladder tumor associated with remarkable granulocytosis in a
      patient who has survived without recurrence for more than 2 years since
      undergoing resection. The patient had remarkable leukocytosis of 51,500/mm(3)
      with 89% granulocytes and an elevated granulocyte-colony stimulating factor (G
      CSF) level of 800 pg/dl. We performed cholecystectomy with extended right
      lobectomy of the liver and lymph node dissection. A histological diagnosis of
      moderately differentiated gallbladder carcinoma with sarcomatous change invading
      the hepatic parenchyma was confirmed. An immunohistochemical examination using
      polyclonal antibody against G-CSF was performed to stain the tumor cells, which
      confirmed the diagnosis of a G-CSF-producing tumor.

PMID- 15976959
TI  - Mesenteric paraganglioma: report of a case.
AB  - We report a rare case of a solitary primary paraganglioma arising in the
      mesentery, found in a 72-year-old woman who presented with abdominal pain and a
      palpable abdominal mass. This extra-abdominal paraganglioma developed from
      paraganglionic cells that travelled by vertebral migration from the root of the
      superior mesenteric artery. Extra-adrenal paraganglia extend anywhere from the
      neck down to the base of the pelvis. Ultrasonography, computed tomography (CT),
      and angiography showed a solid and cystic heterogeneously enhanced mass, which
      was fed by the superior mesenteric artery, without distant metastasis.
      Exploratory laparotomy revealed a large, dark, brownish-red mass in the mesentery
      of the ileum, which was distinct from the ileum. The mass consisted of
      peripherally solid areas with central hemorrhage and cystic degeneration. It was
      diagnosed as a paraganglioma histologically. The patient is free from recurrence
      of paraganglioma after 1 year of follow up. To our knowledge, this represents
      only the seventh case of a paraganglioma arising in the mesentery.

PMID- 15976960
TI  - Laparoscopy-assisted low anterior resection with a prolapsing technique for low
      rectal cancer.
AB  - Laparoscopy-assisted low anterior resection (LAR) for low rectal cancer is a
      difficult procedure, presenting problems with rectal washout, selecting the
      appropriate distal transection line, and achieving safe anastomosis. To resolve
      these problems, we used a prolapsing technique to perform laparoscopy-assisted
      LAR. Total mesorectal excision (TME) is performed laparoscopically. The proximal
      colon is transected laparoscopically with the aid of an endoscopic stapler, and
      the distal rectum, including the lesion, are everted and pulled transanally to
      outside the body. Only washout of and wiping off the distal rectum and intestinal
      resection are performed extracorporeally. The distal rectum is pushed back
      through the anus into the pelvis, and intracorporeal anastomosis is completed
      laparoscopically with a double-stapling technique. Our limited experience
      suggests that the prolapsing technique helps to prevent problems with laparoscopy
      assisted LAR in selected patients with low rectal cancer.

PMID- 15976961
TI  - In vitro platelet responsiveness to adenosine-mediated "preconditioning" is age
      dependent.
AB  - BACKGROUND: Brief preconditioning (PC) ischemia, in addition to its well
      described cardioprotective effects, has been shown in some studies to act on
      circulating platelets and attenuate platelet adhesion and aggregation in models
      of unstable angina and acute myocardial infarction. This "anti-platelet" effect
      of PC may be triggered by release of adenosine from ischemic/reperfused
      myocardium and activation of adenosine A(2) receptors on the platelets' surface.
      However: (1) all current data on the platelet inhibitory effects of PC ischemia
      and A(2) receptor stimulation have been obtained in adult populations; and (2)
      there is evidence of age-associated alterations in myocardial adenosine release,
      receptor responsiveness and post-receptor signaling. OBJECTIVE: Our aim was to
      evaluate, using an established in vitro model of platelet aggregation and
      exogenous administration of an adenosine A(2) agonist, whether the favorable
      effects of adenosine A(2) receptor stimulation on platelet responsiveness are
      compromised in aging populations. METHODS: Arterial blood samples were obtained
      from young adult versus old rabbits (6 months versus 4 years of age) and young
      adult versus senescent rats (4 months versus 2 years of age). Matched aliquots
      from each animal were randomly assigned to receive exogenous treatment with
      either the A(2) agonist CGS 21680 or vehicle. Maximum platelet aggregation was
      quantified by whole blood impedance aggregometry, using collagen as the
      aggregatory stimulus. RESULTS: In young adult rabbits, maximum platelet
      aggregation was, as expected, reduced by 30 +/- 4% in CGS-treated aliquots versus
      vehicle-controls. In contrast, blood samples from 4 year old rabbits were
      refractory to A(2) receptor stimulation: in the old cohort, treatment with CGS
      evoked no change in platelet aggregation (decrease of 2 +/- 3% versus age-matched
      vehicle controls; p < .01 versus the decrease of 30% seen in young adults). Data
      obtained in the rat model were analogous to those seen in the rabbit: maximum
      platelet aggregation decreased by 18 +/- 5% versus 1 +/- 7% with CGS treatment in
      young adult versus senescent animals. CONCLUSION: Our results provide novel in
      vitro evidence of an age-associated loss in platelet responsiveness to adenosine
      mediated "preconditioning".

PMID- 15976963
TI  - Evaluation of coronary artery patency using cardiac markers.
AB  - The availability of a reliable marker of infarct-related artery (IRA) patency
      status may permit early identification of patients with patent IRA, for whom
      repeat thrombolysis or rescue percutaneous coronary intervention (PCI) may not be
      necessary. We found that the ratio of serum myoglobin levels obtained before and
      60-min after initiation of thrombolytic therapy provides a useful indication of
      the IRA patency status. When the 60-min myoglobin ratio was >4.0, the probability
      of a patent IRA was 90%, suggesting that emergency coronary angiography to
      determine their IRA status may be unnecessary when this pattern of release of
      myoglobin is observed. The low specificity of this marker could be addressed by
      its combined use with other noninvasive tests such as ST-segment resolution and
      the persistence of chest pain at the time of angiography.

PMID- 15976962
TI  - Identification, diagnosis and treatment of heparin-induced thrombocytopenia and
      thrombosis: a registry of prolonged heparin use and thrombocytopenia among
      hospitalized patients with and without cardiovascular disease. The Complication
      After Thrombocytopenia Caused by Heparin (CATCH) Registry steering committee.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is estimated to occur in 1-5%
      of all patients receiving heparin, and 25-50% of such cases develop heparin
      induced thrombocytopenia with thrombosis (HITT) A conservative estimate based
      only on cardiovascular patients suggests that in the United States approximately
      100,000 patients develop thrombocytopenia, and 25-50,000 develop HITT annually.
      Both HIT and HITT are associated with high morbidity and mortality and represent
      substantial worldwide public health concerns. REGISTRY DESIGN: The objective of
      the Complication After Thrombocytopenia Caused by Heparin (CATCH) Registry is to
      identify the incidence of HIT and/or HITT in patients treated with systemic
      heparin (unfractionated or low molecular weight heparin) in contemporary
      practice. Additional objectives include to: (1) provide a comprehensive database
      of patients with suspected HIT or HITT, (2) monitor and define clinical events,
      including thrombocytopenia, thrombosis, and mortality among patients treated with
      prolonged (> 96 hours) heparin, (3) describe the incidence and outcomes of HIT
      and HITT in patients who are treated with heparin and who develop
      thrombocytopenia in the Coronary Care Unit setting, and (4) document and
      characterize current diagnostic and therapeutic strategies of suspected HIT. The
      unblinded registry will record approximately 5,000 patients at 60-80 US hospitals
      with either prolonged systemic heparin administration or thrombocytopenia and
      those with suspected HIT or HITT. Enrollment began in the first quarter 2003 and
      was completed at the end of 2004. IMPLICATIONS: The registry will provide
      valuable insights to the incidence and consequences of HIT and HITT that will
      enable improvements in diagnosis and treatment.

PMID- 15976964
TI  - The Bad Oeynhausen concept of INR self-management.
AB  - BACKGROUND: A significant number of patients depend on the intake of vitamin K
      antagonists for prevention and treatment of thromboembolic events. The
      development of portable anticoagulation monitors has enabled self-testing and
      self-adjustment of anticoagulation therapy. OBJECTIVE: To describe the principles
      of a training course to learn INR self-management and to illustrate reliability
      of our concept. DESCRIPTION: The training is divided into an early postoperative
      training, an ambulatory training six months later, and a 24 hours care and
      consultation. According to our concept, each patient who depends on long-term
      anticoagulation therapy is able to learn INR self-management. Reliability of our
      concept has been proved in two prospective, randomized clinical trials. STUDY
      RESULTS: A study with 1,155 patients has demonstrated that INR values lie more
      often in the predetermined target range in the INR self-management group if
      compared to the conventional group (79.2% vs. 64.9%; P < 0.001). Moreover, this
      study has demonstrated that self-management can lead to a reduction of
      thromboembolism (1.5% vs. 2.8%; P < 0.05), and to a lower lethality if compared
      to conventional INR management (3.5% vs 6.0%; P < 0.025). A second study with
      1,816 patients has confirmed that INR self-management results in a high
      percentage of INR values in the target range (76%), even though target INR-range
      is reduced and narrowed. Thus, low dose INR self-management did not increase the
      risk of thromboembolism while avoiding the zone of higher risk for bleeding,
      beginning from INR > 3.5. CONCLUSIONS: The Bad Oeynhausen concept of INR self
      management is a promising tool to achieve low hemorrhagic complications without
      increasing the risk of thromboembolic complications. It can thus be successfully
      applied to patients with an indication for permanent anticoagulation therapy.

PMID- 15976965
TI  - Thrombolysis and counterpulsation to improve survival in myocardial infarction
      complicated by hypotension and suspected cardiogenic shock or heart failure:
      results of the TACTICS Trial.
AB  - BACKGROUND: Sustained hypotension, cardiogenic shock, and heart failure all imply
      a poor prognosis in acute myocardial infarction (MI). We assessed the benefit of
      adding 48 hours of intra-aortic balloon counterpulsation (IABP) to standard
      treatment for MI, in an international trial among hospitals without primary
      angioplasty capabilities. METHODS: We randomized 57 patients with MI complicated
      by sustained hypotension, possible cardiogenic shock, or possible heart failure
      to receive either fibrinolytic therapy and IABP or fibrinolysis alone. The
      primary end point was all-cause mortality at 6 months. RESULTS: In all, IABP was
      inserted in 27 of 30 assigned patients a median 30 minutes after fibrinolysis
      began and continued for a median 34 hours. Of the 27 patients assigned to
      fibrinolysis alone, 9 deteriorated such that IABP was required. The IABP group
      was at slightly higher risk at baseline, but the incidence of the primary end
      point did not differ significantly between groups (34% for combined treatment
      versus 43% for fibrinolysis alone; adjusted P = 0.23). Patients with Killip class
      III or IV showed a trend toward greater benefit from IABP (6-month mortality 39%
      for combined therapy versus 80% for fibrinolysis alone; P = 0.05). CONCLUSIONS:
      While early IABP use was not associated with a definitive survival benefit when
      added to fibrinolysis for patients with MI and hemodynamic compromise in this
      small trial, its use suggested a possible benefit for patients with the most
      severe heart failure or hypotension. ABBREVIATED ABSTRACT: We assessed the
      benefit of adding 48 hours of intra-aortic balloon counterpulsation to
      fibrinolytic therapy among 57 patients with acute myocardial infarction
      complicated by sustained hypotension, possible cardiogenic shock, or possible
      heart failure. The primary end point, mortality at 6 months, did not differ
      between groups (34% for combined treatment versus 43% for fibrinolysis alone [n =
      27]; adjusted P = 0.23), although patients with Killip class III or IV did show a
      trend toward greater benefit from IABP (39% for combined therapy versus 80% for
      fibrinolysis; P = 0.05).

PMID- 15976966
TI  - Predictors of revascularization among emergency department patients who are
      evaluated for acute coronary syndrome.
AB  - BACKGROUND: To determine, among patients who present to the emergency department
      with symptoms suggestive of acute coronary syndrome (ACS), predictors of short
      term revascularization. METHODS: A prospective descriptive trial was performed.
      Potential predictors for revascularization were measured by means of a
      questionnaire of providers, serum for cardiac biomarkers, and an initial ECG. The
      primary outcome of revascularization (coronary bypass graft or percutaneous
      intervention) was determined through a medical record review. Potential
      predictors of revascularization were entered into a family of logistic
      regressions. RESULTS: 341 eligible subjects were enrolled, of whom 14% underwent
      revascularization. The predictors of revascularization included ST elevation on
      initial ECG (odds ratio 12.0), and an elevation in troponin I (odds ratio 8.9),
      CKMB (odds ratio 6.8), or myoglobin (odds ratio 4.7) on admission. When all three
      biomarkers competed in the same model, troponin I appeared to be the strongest
      predictor of short-term revascularization. CONCLUSION: In a single site study,
      among emergency department patients with symptoms suggestive of ACS, ST elevation
      on initial ECG and an elevation in troponin I, CK-MB, and myoglobin upon
      presentation all predicted short -term revascularization. Among the three
      biomarkers, elevation in troponin I was the strongest predictor. ABBREVIATED
      ABSTRACT: We conducted a prospective descriptive trial to identify predictors of
      short-term revascularization among 341 emergency department patients who
      presented with symptoms suggestive of ACS. Fourteen percent of the study
      population received revascularization. Predictors of revascularization included
      ST elevation on initial ECG (odds ratio 12.0.), and an elevation in troponin I
      (odds ratio 8.9), CKMB (odds ratio 6.8), or myoglobin (odds ratio 4.7) on
      admission. When all three biomarkers competed in the same model, troponin I
      appeared to be the strongest predictor of short-term revascularization.

PMID- 15976967
TI  - Impact of platelet glycoprotein IIb/IIIa inhibitor therapy on in-hospital
      outcomes and long-term survival following percutaneous coronary rotational
      atherectomy.
AB  - BACKGROUND: Percutaneous coronary rotational atherectomy (PCRA) is a potent
      stimulus of platelet activation and aggregation in vivo. For this reason, many
      patients undergoing PCRA are treated with platelet glycoprotein (GP) IIb/IIIa
      inhibitors. However, there is limited data regarding the ability of GP IIb/IIIa
      inhibitors to reduce ischemic complications of PCRA and no data regarding their
      effect on long-term survival. METHODS: Data on 1138 consecutive patients
      undergoing PCRA in 5 hospitals in 1998-1999 were pooled and analyzed. Long-term
      survival was available for all 530 patients treated in 3 of the hospitals.
      RESULTS AND CONCLUSIONS: GP IIb/IIIa inhibitors were administered to 315 of 1138
      (28%) PCRA patients. There was no difference in age, gender or race among
      patients treated with and without GP IIb/IIIa antagonists. The prevalence of
      hypertension, diabetes, renal insufficiency and peripheral vascular disease did
      not differ between groups. Unstable angina was more common among patients treated
      with GP IIb/IIIa inhibitors (45% vs. 38%, P = 0.036) Patients treated with GP
      IIb/IIIa inhibitors had lower ejection fractions (50% vs. 55%, P < 0.001) and
      more 3-vessel coronary disease (24% vs. 16%, P = 0.002). Angiographic success was
      over 99% in both groups (P = NS). The frequency of major adverse cardiovascular
      events (MACE) was slightly greater in GP IIb/IIIa inhibitor treated patients
      (3.8% vs. 2.2%, P = 0.126). At a mean follow-up of 3 years, mortality was 13.3%
      in the GP IIb/IIIa treated patients and 12% in the untreated patients (P =
      0.224). On Cox proportional hazards analysis, treatment with a GP IIb/IIIa
      inhibitor was not significantly associated with increased survival (Hazard Ratio,
      0.81, 95% Confidence Interval, 0.631-1.039, P = 0.098). These data do not
      indicate a significant association between GP IIb/IIIa inhibitor treatment during
      PCRA and MACE or survival. CONDENSED ABSTRACT: There is limited data regarding
      the ability of GP IIb/IIIa inhibitors to reduce ischemic complications of
      percutaneous coronary rotational atherectomy (PCRA) and no data regarding their
      effect on long-term survival. These data do not indicate a significant
      association between GP IIb/IIIa inhibitor treatment during PCRA and MACE or
      survival.

PMID- 15976968
TI  - Continuous monitoring of middle cerebral artery recanalization with transcranial
      color-coded sonography and Levovist.
AB  - BACKGROUND AND PURPOSE: Treatment of acute ischemic stroke with intravenous
      recombinant tissue plasminogen activator (rtPA) is relatively ineffective in
      patients with large vessel occlusion. Numerous experimental studies have
      demonstrated that ultrasound (US) can accelerate enzymatic fibrinolysis and
      acceleration of lysis by US is enhanced in the presence of microbubbles used as
      echo-contrast agents. The purpose of this study was to evaluate the feasibility
      of continuous monitoring of middle cerebral artery (MCA) recanalization using
      transcranial color-coded sonography (TCCS) and intravenously administered
      microbubbles. METHODS: Recanalization of middle cerebral artery (MCA) mainstem
      occlusion was assessed using continuous monitoring with TCCS and intravenously
      administered galactose-based microbubbles (Levovist) in 8 consecutive patients
      with acute ischemic stroke treated with intravenous rt-PA within 3 hours of
      symptom onset. RESULTS: Recanalization at one hour occurred in 4 of 8 patients.
      The median NIHSS score was 21 (range 10 to 28) at baseline, 15 (range 0 to 24) at
      1 h, and 11 (range 0 to 22) at 24 h. Asymptomatic hemorrhagic transformation (HT)
      was demonstrated on brain imaging in 6 patients. CONCLUSION: This study
      demonstrates the feasibility of continuous monitoring of MCA recanalization using
      TCCS and Levovist, in acute stroke patients. The findings suggest a high rate of
      asymptomatic HT in monitored patients. Although all HTs were asymptomatic and did
      not preclude early clinical improvement, particular attention should be given to
      the incidence and clinical significance of HT in future studies using these
      methods.

PMID- 15976969
TI  - Is tissue-plasminogen activator gene polymorphism a risk factor for venous
      thromboembolism in every population?
AB  - BACKGROUND: Tissue-plasminogen activator is a key protein of fibrinolytic system.
      In recent years the relation between t-PA, its genetic polymorphisms and arterial
      or venous thrombosis were investigated in different populations. The aim of this
      study is to investigate the role of t-PA gene polymorphism in Turkish venous
      thromboembolism (VTE) patients. METHODS: A case-control study was performed. We
      investigated the t-PA insertion/deletion (I/D) polymorphism in 93 VTE patients
      and 146 controls without VTE. Recurrent cases and documented risk factors for PTE
      were recorded. RESULTS: Cases and controls did not differ with respect to the
      different t-PA genotypes. The prevalence of I allele was 44.1%, 44.5% in cases
      and controls respectively (OR = 0.95, 95% CI: 0.78-1.24, p > 0.05). Different t
      PA genotypes had no effect on recurrent disease. No gender difference was
      observed with respect to the different t-PA genotypes. There was no significant
      difference for genotype frequency between PTE patients with documented risk
      factors and unprovoked cases. CONCLUSIONS: In conclusion there was no association
      between t-PA genotype and VTE in this group of Turkish population. It was also
      found that genotype frequencies for t-PA in both VTE and control subjects seems
      different from those reported from western part of the world. ABBREVIATED
      ABSTRACT: The aim of this study is to investigate the role of t-PA gene
      polymorphism in Turkish VTE patients. We investigated 93 VTE patients and 146
      controls without VTE. Cases and controls did not differ with respect to the
      different t-PA genotypes. The prevalence of I allele was 44.1%, 44.5% in cases
      and controls respectively (OR = 0.95, 95% CI: 0.78-1.24, p > 0.05). Different t
      PA genotypes had no effect on recurrent disease. No gender difference was
      observed with respect to the different t-PA genotypes. There was no significant
      difference for genotype frequency between PTE patients with documented risk
      factors and unprovoked cases. In conclusion there was no association between t-PA
      genotype and VTE in this group of Turkish population. It was also found that
      genotype frequencies for t-PA in both VTE and control subjects seems different
      from those reported from western part of the world.

PMID- 15976970
TI  - Treatment of patients with a history of heparin-induced thrombocytopenia and anti
      lepirudin antibodies with argatroban.
AB  - Patients with heparin-induced thrombocytopenia (HIT) type II require
      anticoagulation with non-heparin immediate acting anticoagulants. Danaparoid may
      cross react with HIT-antibodies and lepirudin may generate anti-lepirudin
      antibodies influencing anticoagulation. We hypothesised, that the synthetic small
      molecular thrombin inhibitor argatroban does not induce immunoglobulins reacting
      towards lepirudin in patients with anti-lepirudin antibodies in the history and
      that titration of the anticoagulation may be easier with argatroban. We report on
      the treatment of four patients of a study, which was terminated prematurely due
      to official warnings for a repeated use of lepirudin. Two patients each received
      argatroban and lepirudin intravenously. A blinded assessor adjusted the doses of
      the anticoagulants to 1.5-3.0 fold prolongation of the aPTT. Ecarin clotting time
      (ECT), concentrations of lepirudin (ELISA) and of argatroban (gas-chromatography
      with mass spectrometry), and the generation of lepirudin antibodies (ELISA) were
      measured. APTT-adjusted dosages for argatroban was 2.0-2.6 microg/kg.min and for
      lepirudin 48-149 microg/kg.h. ECT was prolonged 2.1 to 4.5-fold with lepirudin
      and 4 to 7-fold with argatroban. The concentration of lepirudin ranged between
      750 and 1500 ng/ml and of argatroban between 400 and 1100 ng/ml. Patients on
      argatroban did not generate immunoglobulin IgG reacting towards lepirudin in
      contrast to both patients on lepirudin who developed anti-lepirudin antibodies.
      Both treatments were well tolerated. Despite the low number of patients
      argatroban seems to lead to a more stable anticoagulant response than lepirudin
      resulting in a lower variability of the dosage for prophylaxis or treatment of
      thromboembolism of patients with a history of HIT and lepirudin antibodies.

PMID- 15976971
TI  - Biomarkers in atrial fibrillation: investigating biologic plausibility, cause,
      and effect.
AB  - Atrial fibrillation, an increasingly common arrhythmia whose prevalence will
      reach epidemic proportions over the next two decades, is characterized by
      atrial/atrial appendage inflammation, fibrosis, remodeling, and endocardial
      thrombosis. Biomarkers measured within the peripheral circulation reflect these
      pathobiologic events with evidence of heightened thrombin generation and
      activity, platelet activity, fibrin formation, endocardial injury, inflammatory
      mediator release, and reduced fibrinolytic potential Unfortunately, the
      correlation between traditional biomarkers and clinical events is weak at best,
      as is their ability to predict successful treatment (prevention of
      cardioembolism) with antithrombotic agents. Future efforts devoted to the
      investigation of cellular biomarkers will likely provide greater practical yield
      and insights concerning the development, diagnosis, prognosis, and management of
      atrial fibrillation.

PMID- 15976972
TI  - Conflict of interest-draining the swamp means confronting alligators.

PMID- 15976973
TI  - Venous thrombosis and stenosis after implantation of pacemakers and
      defibrillators.
AB  - Venous complications of pacemaker/ implantable cardioverter defibrillator (ICD)
      system implantation rarely cause immediate clinical problems. The challenge
      starts when patients come for system revision or upgrade. Numerous reports of
      venous complications such as stenosis, occlusions, and superior vena cava
      syndrome have been published. We reviewed current knowledge of these
      complications, management, and their impact on upgrade/revision procedures. One
      study has suggested that intravenous lead infection promotes local vein stenosis.
      Another found that the presence of a temporary wire before implantation is
      associated with an increased risk of stenosis. Although data for ICD leads is
      based only on three studies-it suggests that the rate of venous complications is
      very similar to that of pacing systems, and probably data from pacing leads can
      be extrapolated to ICD leads. Despite 40 years of experience with transcutaneous
      implanted intravenous pacing systems and dozens of studies, we were unable to
      identify clear risk factors (confirmed by independent studies) that lead to
      venous stenosis. Neither the hardware (lead size, number and material) nor the
      access site choice (cephalic cut down, subclavian or axillary puncture) appears
      to affect rate of venous complications. A few factors were proposed as predictors
      of severe venous stenosis/occlusion: presence of multiple pacemaker leads
      (compared to a single lead), use of hormone therapy, personal history of venous
      thrombosis, the presence of temporary wire before implantation, previous presence
      of a pacemaker (ICD as an upgrade) and the use of dual-coil leads. Anticoagulant
      therapy (for other reasons than pacemaker lead) seemed to have protective
      antithrombotic effect.

PMID- 15976974
TI  - Experimental model of inappropriate sinus tachycardia: initiation and ablation.
AB  - OBJECTIVE: The purpose of the present study was to develop an experimental model
      of inappropriate sinus tachycardia (IST) by injecting a catecholamine into a fat
      pad containing autonomic ganglia (AG) innervating the sinus node (SN). METHODS:
      Initial protocols in 3 groups of pentobarbital anesthetized dogs consisted of (1)
      slowing the heart rate (HR) by electrical stimulation of AG in the fat pad; (2)
      the effect of intravenous injection of epinephrine (0.1-0.3 mg) on the HR and
      systolic blood pressure (BP); (3) the response of SN rate to intravenously
      injected isoproterenol (1 microgm/kg). These studies established a reference for
      the response to epinephrine injection (mean dose 0.2 +/- 0.9 mg, n = 14) into the
      fat pad at the base of the right superior pulmonary vein (RSPV). ECG leads, right
      atrial and His bundle electrograms, BP and core body temperature were
      continuously monitored. RESULTS: Epinephrine, injected into the fat pad, caused a
      significant increase in heart rate (HR, average: 211 +/- 11/min, p < 0.05
      compared to control) but little change in systolic BP, 149 +/- 10 mmHg, p = NS
      (Group I, N = 8). The tachycardia lasted >30 minutes. Ice mapping and P wave
      morphology showed the tachycardia origin in the SN in 6/8 and in the crista
      terminalis (CT) in 2. Injection of 0.4 cc of formaldehyde into the FP restored HR
      (159 +/- 16) toward baseline (154 +/- 18). In Group II (N = 6), the same regimen
      induced a significant increase in both HR and systolic BP (194 +/- 17/min and 230
      +/- 24 mmHg, respectively) compared to control values (143 +/- 23/min, 162 +/- 24
      mmHg) which lasted for > 30 minutes. Ice mapping and P wave morphology showed
      that the pacemaker was in the SN (1), overlying the CT (2), or atrioventricular
      junction (2). Formaldehyde (0.4 cc) injected into the FP restored both HR and
      systolic BP toward baseline values (148 +/- 29/min and 152 +/- 24 mmHg, p = NS)
      and prevented, slowing of the HR by electrical stimulation of the AG; moreover,
      the same dose of epinephrine injected intravenously increased HR and SBP but only
      for 2-5 minutes; Isoproterenol (1 microg/kg) injected intravenously induced
      essentially the same increase in sinus rate after AG ablation as in the control
      state (194 +/- 15/min vs 193 +/- 23/min, p = NS). CONCLUSION: Experimental IST is
      mainly localized in the SN or CT. Ablation of the AG terminates IST without
      impairing the SN response to an adrenergic challenge.

PMID- 15976975
TI  - Targeting atrio-atrial conduction in the post-orthotopic heart transplant
      patient.

PMID- 15976976
TI  - Safety and feasibility of coronary sinus left ventricular leads extraction: a
      preliminary report.
AB  - BACKGROUND: transvenous positioning of the left ventricular (LV) lead in a branch
      of the coronary sinus (CS) is generally the preferred implantation technique in
      biventricular pacing. Very few data are reported about removal of LV pacing leads
      positioned in a CS branch. Aim of the study was to describe our experience with
      percutaneous extraction of LV pacing leads in order to evaluate feasibility and
      safety of this procedure. METHODS: we enrolled 392 patients who underwent a
      biventricular pacing implant. The indication for catheter removal was considered
      in case of definite diagnosis of infection and in some cases of lead dislodgement
      or diaphragmatic stimulation. LV lead extraction was first attempted by manual
      traction; in case of failure a locking stylet or locking stylet plus
      radiofrequency could be used. RESULTS: twelve of 392 patients implanted needed LV
      lead removal. The leads had been in place for 13.9 +/- 11.7 months. Extraction
      was indicated in 5 of them for LV lead dislodgement or diaphragmatic stimulation,
      and in 7 patients for lead infection. In all cases manual traction succeeded to
      remove the LV lead. In 7 cases of infection, the right atrial and ventricular
      leads were removed. The mean total procedure time was 69 +/- 22 min. No
      complications were observed. CONCLUSIONS: our study suggests that CS leads could
      be easily and safely removed without any complication, also when placed in a CS
      branch, at least for relatively young catheters.

PMID- 15976978
TI  - Deployment of left ventricular lead from the ipsilateral side of central vein
      obstruction.
AB  - Cardiac resynchronisation therapy improves symptoms and reduces mortality in
      patients with chronic heart failure. In patients with previously implanted
      devices, particularly automatic defibrillators, central venous stenoses provide a
      challenge to upgrading to resynchronisation devices. We present a patient with
      central venous obstruction secondary to previously implanted defibrillator leads,
      in whom we achieved coronary sinus pacing through the ipsilateral internal
      jugular vein.

PMID- 15976977
TI  - Right ventricular outflow tract pacing: not ready for prime-time.

PMID- 15976979
TI  - Atrial pacing failure following termination of atrial fibrillation by acute
      administration of disopyramide phosphate.
AB  - Atrial pacing failure occurred after termination of atrial fibrillation by acute
      administration of disopyramide phosphate in a 71-year-old woman implanted with an
      AAI pacemaker for sick sinus syndrome. The atrial pacing threshold showed an 810%
      increase; however, the serum concentration of disopyramide corresponded to
      therapeutic level. Infusion of the same dose of disopyramide phosphate used
      during the period of atrial pacing rhythm did not increase the atrial pacing
      threshold. In the present patient, we supposed that atrial pacing failure did not
      occur by the effect of disopyramide alone, but rather was a reciprocal action in
      response to atrial fibrillation.

PMID- 15976980
TI  - Repositioning of a dislodged and fibrosed ventricular lead.
AB  - This is a case of a 61 year old African American female with history of end stage
      renal disease on hemodialysis. She had a dual chamber permanent pacemaker
      implanted in 2003 for symptomatic bradycardia. Over the past several months the
      patient had problems with access for dialysis. The right arm AV fistula was
      occluded. The patient had multiple temporary central catheter placed for dialysis
      over the past 3 months. The patient was admitted for superior vena-cava syndrome.
      CT scan of the thorax and neck showed occluded right and left subclavian system.
      An incidental finding was the right ventricular (RV) lead been dislodged and the
      tip being in the inferior vena cava. Surgical and non-surgical options were
      discussed with the patient and she chose to go the less invasive route. The
      patient underwent a RV lead revision. Using different stylets the RV lead was
      repositioned in the RV with good pacing and sensing characteristics. CONCLUSIONS:
      Successful repositioning of an old dislodged RV pacing lead using stylets and
      eliminating the need for invasive procedure like lead extraction.

PMID- 15976981
TI  - Comparison between a 7 French 6 mm tip cryothermal catheter and a 9 French 8 mm
      tip cryothermal catheter for cryoablation treatment of common atrial flutter.
AB  - BACKGROUND: Larger tipped cryothermal catheters may deliver efficacy and
      procedure benefits in the treatment of patients with atrial flutter. OBJECTIVE:
      To compare 7 French 6 mm and 9 French 8 mm tip cryothermal catheters (Freezor,
      Xtra or Freezor, MAX, CryoCath Technologies Inc., Kirkland, Canada) in terms of
      acute and chronic efficacy, and procedure characteristics in the treatment of
      atrial flutter. METHODS: This non-randomized clinical investigation determined bi
      directional isthmus block at intervention, procedure characteristics, and symptom
      and conduction recurrence rates post procedure in consecutive patients with
      symptomatic atrial flutter ablated either with the 7 French 6 mm tip cryothermal
      catheter (n = 43) at -75 degrees C for 4 minutes or the 9 French 8 mm tip
      cryothermal catheter (n = 51) at -75 degrees C for 8 minutes. RESULTS: Clinical
      data showed a higher acute success rate for the larger tipped catheter (100% vs.
      88%). Symptom recurrence rates were 0% for both catheters at 3, 6, and 9 month
      follow-up. Conduction recurrence rates were similar for both catheters on repeat
      electrophysiological study at 3 months post procedure (35% vs. 32%). Procedure
      benefits were fewer cryotests (20 +/- 17 vs. 26 +/- 21) and ablations (4 +/- 4
      vs. 12 +/- 18), and shorter procedure (80 +/- 61 min vs. 87 +/- 48 min),
      fluoroscopy (14 +/- 9 min vs. 24 +/- 10 min), and cryoapplication times (37 +/-
      18 min vs. 44 +/- 23 min) with the larger tipped catheter. There were no adverse
      events reported. CONCLUSIONS: Clinical results showed differences in catheter
      performance that favoured the larger tipped catheter. However, increased acute
      success rate did not translate into reduced conduction recurrence rate post
      ablation, although clinical recurrence was completely absent long-term.

PMID- 15976982
TI  - Coexistence of intracardiac atrial flutter and extracardiac fibrillation.
AB  - This report describes the coexistence of fibrillatory activity limited to an
      isolated left common pulmonary vein trunk with typical counterclockwise isthmus
      dependent right atrial flutter in a patient undergoing a pulmonary vein isolation
      procedure.

PMID- 15976983
TI  - Inappropriate implantable cardioverter defibrillator shock from a transcutaneous
      muscle stimulation device therapy.
AB  - Inappropriate shock from implantable cardioverter defibrillator (ICD) may result
      from external electromagnetic interference (EMI), especially for unipolar
      ventricle sensing. Previous case reports and small in-vitro safety study
      suggested that endocardial bipolar lead system may be immune from EMI resulting
      from transcutaneous electrical neuromuscle stimulation (TENS) therapy. This
      report presents an unusual case of inappropriate discharge in a patient with ICD
      of endocardial bipolar lead system, receiving TENS from a commercially available
      device.

PMID- 15976984
TI  - History. Guy Fontaine. Richard Wagner.

PMID- 15976986
TI  - Dr. George Hayward (1791-1863): a forgotten pioneer of reconstructive pelvic
      surgery.
AB  - American surgeon George Hayward (1798-1863) has become lost to the historical
      memory of practicing urologists and urogynecologists, yet he deserves to be
      remembered for his important contributions to the advancement of pelvic surgery.
      In addition to being an observant commentator on the surgical practice of his
      day, he performed the first major operation carried out under ether anesthesia
      and he was the originator of the "flap-splitting" operation for the repair of
      vesico-vaginal fistula commonly, but erroneously, attributed to Lawson Tait. This
      article reviews George Hayward's career and professional accomplishments with the
      hope of restoring his well-deserved prominence as a pioneer of reconstructive
      pelvic surgery.

PMID- 15976987
TI  - The choice of elective cesarean delivery in obstetrics: a voluntary survey of
      Canadian health care professionals.
AB  - To survey Canadian health care professionals about their willingness to offer
      elective cesarean delivery and to evaluate how their knowledge of obstetric
      related pelvic-floor injury influences their practice. A voluntary questionnaire
      was distributed to health care professionals attending the 58th Annual Meeting of
      the Society of Obstetricians and Gynaecologists of Canada in 2002. Appropriate
      statistical analysis was used. One hundred and sixty-two questionnaires were
      completed. One hundred respondents were female (62%). Twenty-three percent
      (37/162) of respondents approved elective cesarean delivery after informed
      request in nulliparous women without an obstetrical indication. Males were more
      likely than females to perform cesarean delivery in these circumstances (34%
      versus 16%; OR 2.7, CI 1.2, 6.0). When questioned about the impact of mode of
      delivery on bladder and bowel continence, the number of respondents who answered
      "usually" or "always has a detrimental effect" were: vaginal birth, 16%; forceps,
      20%; and cesarean delivery "reduces bladder and bowel problems", 44%. Males were
      more likely to emphasize a protective effect of cesarean delivery (55% versus
      38%; OR 1.9, CI 1.0, 4.0). Health care professionals would opt for cesarean
      delivery for themselves when forceps delivery was the alternative more often than
      they would offer cesarean delivery to their patients (OR 1.98, CI 1.1, 3.5).
      While a significant number of women's health care professionals are prepared to
      offer cesarean delivery to nulliparous women, informed choice seems to motivate
      the offer rather than a conviction that cesarean delivery will protect the pelvic
      floor.

PMID- 15976988
TI  - Association of quantitative heel ultrasound with history of osteoporotic
      fractures in elderly men: the ESOPO study.
AB  - In order to evaluate the usefulness of calcaneal quantitative ultrasound (QUS) in
      the assessment of male osteoporosis, a cross-sectional, population-based study
      was performed. A cohort of 4,832 men, randomly selected, community-dwelling, aged
      60-80 years and representative of the general older male Italian population was
      recruited. QUS measurements were assessed in 83 centers distributed all over
      Italy and equipped with an Achilles device (GE-Lunar, Madison, Wisconsin, USA).
      All participants were administered a questionnaire covering lifestyle variables
      and medical history. Low-energy fractures that had occurred since age 50 were
      recorded. Overall, 43 subjects reported a previous hip fracture and 455 subjects
      reported other non-spinal fractures. Univariate analysis showed that fractured
      subjects were older, with a lower level of outdoor physical activity and a more
      frequent history of prolonged bedridden periods in comparison with unfractured
      subjects. Men reporting non-spinal fractures showed a higher prevalence of
      smoking, while no difference was found among groups in anthropometric measures
      and calcium intake. QUS measurements showed that all QUS parameters were
      significantly lower in both fracture groups (p<0.001). Multiple logistic
      regression analysis demonstrated that each SD reduction in QUS measures was
      associated with an approximate doubling of the risk for hip fracture, independent
      of age and other clinical variables (broadband ultrasound attenuation [BUA]: odds
      ratio [OR]=2.24; 95% confidence interval [CI] 1.61-3.08; stiffness index:
      OR=2.19; CI 1.56-3.11; speed of sound [SOS]: OR=1.71; CI 1.18-3.24) and with an
      increase of the risk of other non-spinal fractures (BUA: 1.38; CI 1.22-1.59;
      stiffness index: OR=1.27; CI 1.17-1.38; SOS: OR=1.14; CI 0.96-1.40). It can be
      concluded that calcaneal QUS measurement is associated with the risk for hip
      fracture and any non-spinal fractures among a community-dwelling cohort of
      elderly men. The strength of the association between QUS measurement and fracture
      is similar to that observed in elderly women.

PMID- 15976989
TI  - Effect of CYP2C19 and MDR1 polymorphisms on cure rate in patients with acid
      related disorders with Helicobacter pylori infection.
AB  - A proton pump inhibitor (PPI) plus two antibiotics (amoxicillin and either
      clarithromycin or metronidazole) are recommended for treatment of acid-related
      disorders with Helicobacter pylori (H. pylori) infection. The aim of this
      pharmacogenetic study was to evaluate the efficacy of triple therapy with PPIs on
      eradication of H. pylori infection in relation to cytochrome P450 2C19 (CYP2C19)
      and P-glycoprotein (MDR1) gene polymorphisms. The retrospective study involved 70
      Polish Caucasian patients with H. pylori infection, diagnosed and treated with
      one of the two different triple therapy regimens [omeprazole, amoxicillin, and
      clarithromycin (OAC) or pantoprazole, amoxicillin, and metronidazole (PAM)].
      Using genomic DNA, CYP2C19 (*2 and *3) and C3435T MDR1 alleles were determined by
      means of polymerase chain reaction-restriction fragment length polymorphism
      assays. A significantly higher prevalence (P<0.05) of heterozygous extensive
      metabolizers (hetEM) with CYP2C19*1/*2 genotype (32.4% versus 8.3%) and
      homozygous with 3435TT MDR1 genotype (38.2% versus 13.9%) was found in patients
      cured after the first cycle of triple therapy than in patients with failure of
      eradication after the first cycle. CYP2C19*1/*2 and 3435TT MDR1 genotypes as well
      as PAM regimen of treatment were also predictive of successful eradication of H.
      pylori infection after the first cycle of triple therapy at
      univariate/multivariate logistic regression analysis. This pharmacogenetic study
      on the influence of different CYP2C19 and C3435T MDR1 genotypes on H. pylori
      eradication suggests that CYP2C19 and MDR1 polymorphisms may be independent
      predictable determinants of the efficacy of triple therapy including PPI. The PAM
      regimen of treatment seems to be more effective after the first cycle of the
      therapy than the OAC regimen.

PMID- 15976990
TI  - How I do it--the Kotecha technique for laser palatoplasty.
AB  - Snoring is a common problem affecting approximately 19% of the general population
      and up to 50% of those over 60 years of age. Surgical techniques to overcome this
      condition have evolved since the introduction of the uvulopalatopharyngoplasty
      procedure described by Ikematsu in 1964 and more recently the laser-assisted
      uvulopalatoplasty by Kamami in 1990. We describe a modified technique that aims
      to shorten and stiffen the soft palate and posterior pillars without destroying
      the natural palatal contour. The advantages of this technique are discussed.

PMID- 15976991
TI  - Manifestations of hereditary hemorrhagic telangiectasia in children and
      adolescents.
AB  - The medical literature provides little information on manifestations of
      hereditary hemorrhagic telangiectasia (HHT) in children. The presented
      investigation was initiated to analyze early presenting symptoms in HHT, which
      should help to make the diagnosis at a young age and thus prevent potential
      complications from occult visceral arteriovenous malformations (AVM), which have
      commonly been described in HHT. A series of 15 children and adolescents with a
      suspicious diagnosis of HHT were examined clinically for typical signs and
      symptoms of the disorder. If the diagnosis of HHT seemed to be likely,
      recommendations for non-invasive screening procedures were given. Screening was
      directed at the detection of occult visceral AVMs. Main outcome measures were the
      definition of principal signs of HHT in children and adolescents. Family history
      was positive for HHT in 13 persons. The principal sign of recurrent epistaxis was
      present in 10/15 individuals and the earliest age of onset with regard to
      epistaxis was 4 years. Cutaneous vascular lesions were present in 5/15 patients.
      Screening for AVMs was performed in six individuals and revealed vascular lesions
      of the brain in two patients and vascular lesions of the lung in two patients.
      Gastrointestinal hemorrhages were present in one infant. Based on these findings,
      diagnosis of HHT seemed likely in ten individuals and unlikely in five
      individuals. Signs and symptoms of HHT in children and adolescents may be
      discrete, but are detectable at an earlier age than previously thought. Clinical
      examinations in children from HHT families may help identify candidates who will
      benefit from molecular genetic testing or screening imaging studies.

PMID- 15976992
TI  - Transtonsillar drainage of parapharyngeal abscess.
AB  - We report a parapharyngeal abscess in an adult patient that was drained
      transorally by performing ipsilateral tonsillectomy and aspirating the pus
      through the tonsillar bed. This approach is unusual as most previous studies
      report the aspiration of such abscesses through the lateral pharyngeal mucosa. In
      addition, the majority of these studies are limited to pediatric cases. Our
      approach was effective and resulted in a rapid resolution of the symptoms. The
      management and different approaches to parapharyngeal abscess are discussed, and
      the literature is reviewed.

PMID- 15976993
TI  - Intranasal trigeminal sensitivity in subjects with allergic rhinitis.
AB  - Trigeminal nerve endings of the human nasal mucosa are activated by chemical,
      physical or thermal stimuli. Activation of these A(delta) and C fibers can be
      quantified through the recording of chemo-somatosensory event-related potentials
      (ERP). The aim of this study was to investigate whether allergy-related
      activation of trigeminal nerve endings leads to changes in their responsiveness
      to intranasal trigeminal stimulation. Gaseous carbon dioxide (CO(2)) stimuli were
      applied in three sessions (baseline, after NaCl solution and after allergen
      application) to the nasal mucosa of 13 subjects with allergic rhinitis. Chemo
      somatosensory ERP were recorded, and subjects rated the intensity of rhinitis
      symptoms. Administration of allergen produced a significant shortening of chemo
      somatosensory ERP peak latencies P1 and N1. Observed changes of latencies were in
      line with rhinitis symptoms subjects indicated during the session. In addition,
      there was a negative relation between the general symptom score and ERP peak
      latencies, obtained both at baseline and after allergen exposure. In conclusion,
      it is hypothesized that in patients suffering from allergic rhinitis, nasal
      itching and sneezing after allergen exposure are, at least in part, clinical
      correlates of the activation of trigeminal nerve endings due to local
      inflammatory mechanisms. The correlations between ERP latencies and the patients'
      symptoms indicate that ERP latencies may possess a predictive value of the
      subjects' responsiveness to allergens.

PMID- 15976994
TI  - Laryngeal repair after resection of advanced cancer: an optimal reconstructive
      protocol.
AB  - Tracheal autotransplantation allows for reconstruction of extended
      hemilaryngectomy defects after resection of laryngeal cancer. With this
      technique, optimal functional results were obtained after a learning curve of
      more than 50 patients. The objective of this paper is to present the final
      reconstructive concept with the typical indications. Unilateral glottic cancer
      and lateralized chondrosarcomas of the cricoid cartilage are resected with a
      hemilaryngectomy including one-half of the cricoid cartilage. After tumor
      resection, a radial forearm flap with a skin paddle and a fascial paddle are
      taken. The skin paddle restores the laryngeal defect temporarily, and the fascial
      paddle wraps the upper 4 cm of cervical trachea. A 'tracheostomy' is preserved in
      the area between the reconstructed larynx and the fascia-wrapped trachea. The
      radial forearm vessels are sutured to the neck vessels. After 4 months, the skin
      island of the radial forearm flap is removed from the defect and the
      revascularized, fascial enwrapped trachea is transplanted to the laryngeal
      defect. The tracheal continuity is re-established with preservation of a
      tracheostoma. The tracheotomy can be closed after 6 weeks. Two case reports are
      presented: a unilateral T3 glottic cancer and a chondrosarcoma of the cricoid
      cartilage. The two patients showed normal oral feeding 1 week after the
      operation. Hand-free speaking was possible after closure of the tracheostomy.
      Tracheal autotransplantation after vascular induction of the trachea with the
      radial forearm flap leads to optimal repair of extended hemilaryngectomy defects.

PMID- 15976995
TI  - Sedative effects of the jasmine tea odor and (R)-(-)-linalool, one of its major
      odor components, on autonomic nerve activity and mood states.
AB  - We investigated the effects of the odor of jasmine tea on autonomic nerve
      activity and mood states in a total of 24 healthy volunteers. We used the odor of
      jasmine tea at the lowest concentration that could be detected by each subject
      but that did not elicit any psychological effects. R-R intervals and the POMS
      test were measured before and after inhalation of the odors for 5 min. Both
      jasmine tea and lavender odors at perceived similar intensity caused significant
      decreases in heart rate and significant increases in spectral integrated values
      at high-frequency component in comparison with the control (P < 0.05). In the
      POMS tests, these odors produced calm and vigorous mood states. We also examined
      the effects of (R)-(-)-linalool, one of its major odor components, at the same
      concentration as in the tea, and (S)-(+)-linalool. Only (R)-(-)-linalool elicited
      a significant decrease in heart rate (P < 0.05) and an increase in high-frequency
      component in comparison with the controls, and produced calm and vigorous mood
      states. Thus, the low intensity of jasmine tea odor has sedative effects on both
      autonomic nerve activity and mood states, and (R)-(-)-linalool, one of its
      components, can mimic these effects.

PMID- 15976996
TI  - A comparison of inspiratory muscle fatigue following maximal exercise in
      moderately trained males and females.
AB  - Exercise-induced inspiratory muscle fatigue (IMF) has been reported in males but
      there are few reports of IMF in females. It is not known if a gender difference
      exists for inspiratory muscle strength following heavy exercise, as is reported
      in locomotor muscles. Therefore, the relationship between fatigue and subsequent
      recovery of maximal inspiratory pressure (MIP) following exercise to maximal
      oxygen consumption (VO2max) was examined in a group of moderately trained males
      and females. Eighteen males (23+/-3 years; mean +/- SD) and 16 females (23+/-2
      years) completed ten MIP and ten maximal handgrip (HG) strength maneuvers to
      establish baseline. Post-exercise MIP and HG were assessed successively
      immediately following a progressive intensity VO2max test on a cycle ergometer
      and at 1, 2, 3, 4, 5, 10, and 15 min. VO2max, relative to fat-free mass was not
      statistically different between males (62+/-7 ml kg(-1) min(-1)) and females
      (60+/-8 ml kg(-1) min(-1)). Males had higher absolute MIP values than females at
      all time intervals (P<0.05). Immediately following exercise, MIP was
      significantly reduced in both genders (M=83+/-16%; F=78+/-15% of baseline) but HG
      values were not different than resting values. MIP values remained depressed for
      both males and females throughout the 15 min (P<0.05). Differences for MIP
      between males and females were not statistically significant at any measurement
      time (P>0.05). The findings in this study conclude that IMF, observed immediately
      following maximal exercise, demonstrated the same pattern of recovery for both
      genders.

PMID- 15976997
TI  - Changes of motor drive, cortical arousal and perceived exertion following
      prolonged cycling to exhaustion.
AB  - The aims of this study were to (1) quantify any central fatigue that occurs
      following prolonged dynamic exercise, i.e. reduced muscle force caused by
      impaired motor drive from the central nervous system and (2) determine whether
      decreased cortical arousal, assessed using critical flicker fusion threshold
      (CFF), occurs and is related to impaired exercise performance. Fifteen healthy
      men cycled at 70% VO2peak until exhaustion. The peak force of maximum voluntary
      isometric contractions (MVC) of the quadriceps muscle group was reduced by 30% at
      exhaustion. The voluntary activation ratio determined using superimposed tetanic
      stimulation fell from 0.99 to 0.86 at exhaustion. The central fatigue (%) at
      exhaustion was 33+/-12% (+/- SD) (assessed via the tetanus interpolation
      technique) and 54+/-32% (assessed via the relative decline of MVC and peak
      tetanic force) of the total fatigue. The MVC only partially recovered and central
      fatigue persisted at 30 min post-exercise. CFF increased from 39.2+/-2.3 to
      41.8+/-3.5 Hz at exhaustion, but did not correlate with central fatigue. Every
      subject reached the highest rating of perceived exertion (RPE) at exhaustion of
      20 on the Borg scale. The time to exhaustion was related to how quickly the RPE
      increased and to the ability to sustain exercise at very high RPE. These data
      suggest that with prolonged cycling: (1) there is considerable and a persistent
      form of central fatigue, (2) there is an increased level of cortical arousal, and
      (3) exhaustion is linked to very high subjective RPE.

PMID- 15976998
TI  - The anthropometrical and physiological characteristics of elite water polo
      players.
AB  - In order to examine the physical and physiological demands of water polo, we
      assessed the profile of elite water polo players. Nineteen male professional
      water polo players (age: 25.5+/-5.0 years, height: 184.5+/-4.3 cm body mass:
      90.7+/-6.4 kg) underwent body composition assessment by dual-energy X-ray
      absorptiometry. We also evaluated peak oxygen consumption VO2peak, lactate
      threshold (LT), energy cost of swimming (C s), anaerobic capacity and isokinetic
      shoulder strength. Body fat (%) was 16.8+/-4.4, lean mass (LM) 75.1+/-4.9 kg and
      bone mineral density (BMD) 1.37+/-0.07 g.cm(-2) . VO2peak was 57.9+/-7 ml.kg(-1).
      min(-1) . LT was identified at 3.9+/-0.7 mmol.l(-1) at a swimming velocity (v) of
      1.33+/-0.05 m.s(-1) with a heart rate of 154+/-7 bpm, corresponding to an
      intensity of 83+/-9 of VO2peak. The average C s of swimming at the LT was 1.08+/
      0.04 kJ.m(-1).C s at LT was correlated to body mass index (BMI) (r=0.22, P=0.04)
      and to swimming performance at 400 m (r=0.86, P=0.01) and 4 x 50 m (r=0.84,
      P<0.01). Internal rotator muscles were stronger compared to the external rotators
      by a 2:1 ratio. This study provides a quantitative representation of both
      physical and physiological demands of water polo and proposes a comprehensive
      battery of tests that can be used for assessing the status of a team.

PMID- 15976999
TI  - Relationship between oxygen uptake kinetics and performance in repeated running
      sprints.
AB  - The purpose of this study was to test the hypothesis that subjects having a
      shorter time constant for the fast component of VO2 kinetics in a transition from
      rest to constant exercise would maintain their speed for a longer time during
      repeated sprint exercise (RSE). Eleven male soccer players completed a graded
      test, two constant exercises at 60% maximal aerobic speed and RSE, consisting of
      fifteen 40-m sprints alternated with 25 s of active recovery. All the tests were
      performed on the field (200 m indoor track). The parameters of the VO2 kinetics
      (time delay, time constant, and amplitude of the primary phase) during the two
      constant exercises were modeled. All subjects elicited VO2 during the RSE. A
      significant correlation was found between VO2 and the relative decrease in speed
      during the 15 sprints (r=0.71; p < 0.05), but not between VO2 and the cumulated
      time for the 15 sprints (r=0.48; p > 0.05). There were significant correlations
      between the time constant of the primary phase and the relative decrease in speed
      during the 15 sprints (r=0.80; p < 0.01) and the cumulated time for the 15
      sprints (r=0.80; p < 0.01). These results suggest that individuals with faster
      VO2 kinetics during constant load exercise might also have a faster adjustment of
      VO2 during RSE leading to a shorter cumulated time and a lower relative decrease
      in speed during the 15 sprints.

PMID- 15977000
TI  - Emotional responding in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal disease, leaving the patient in a
      partially or completely deafferented state. In an explorative study, we
      investigated responses to visual socio-emotional stimuli in ALS patients.
      Pictures from the International Affective Picture System (IAPS) were verbally
      judged by 12 moderately affected ALS patients with a spinal onset and a slow
      progression and 18 age-matched controls, and data were compared with
      psychophysiological responses. Verbal emotional judgments of patients were more
      positive than ratings of controls. Regarding arousal, patients neutralized
      extreme pictures, in that they rated calm pictures as more exciting than controls
      and exciting pictures as more calm. These changes of emotional processing were
      unrelated to depression or frontal lobe dysfunction. There were no major
      differences between patients and controls concerning physiological responses to
      emotional stimuli. We conclude that emotional responses of ALS patients tend to
      be altered towards positive valence and towards a more balanced arousal state in
      early stages of the disease. These findings contradict assumptions of a generally
      negative impact of the disease on the emotional disposition and may indicate
      compensatory cognitive or neuroplastic changes.

PMID- 15977001
TI  - John Hughlings Jackson (1835-1911).

PMID- 15977004
TI  - Impact of the European Antimicrobial Resistance Surveillance System on the
      development of a national programme to monitor resistance in Staphylococcus
      aureus and Streptococcus pneumoniae in Ireland, 1999-2003.
AB  - Presented here is the 5-year impact of a national antimicrobial resistance
      surveillance system in Ireland, which was introduced in accordance with the
      European Antimicrobial Resistance Surveillance System (EARSS). Participation in
      EARSS began in Ireland in 1999. Initially, 12 laboratories serving a mix of
      general and tertiary hospitals participated, but by 2003, participation had
      increased to 28 laboratories with a population coverage of 89%. During 1999-2003,
      4,146 episodes of Staphylococcus aureus bacteraemia were reported, and
      methicillin resistance was detected in 1,709 (41.2%) of these isolates. Over the
      same period, 1,245 invasive (blood or cerebrospinal fluid) episodes of
      Streptococcus pneumoniae infection were reported, and 160 (12.9%) isolates were
      found to be non-susceptible to penicillin, with 23 (1.8%) demonstrating high
      level penicillin resistance. By 2003, most Irish hospitals were participating in
      EARSS, which has been a catalyst for the development of a national antimicrobial
      resistance surveillance programme.

PMID- 15977005
TI  - Acute purulent pericarditis in pneumococcal meningitis.

PMID- 15977006
TI  - [Treatment of mid-clavicular fractures in adults. Early results after rucksack
      bandage or elastic stable intramedullary nailing].
AB  - OBJECTIVES: The aim of this prospective study was to compare the results achieved
      in two groups of patients treated for mid-clavicular fracture. METHODS: The first
      group of 27 patients was treated nonoperatively with a rucksack bandage, whereas
      the second group underwent intramedullary fixation with a titanium pin, using a
      minimally invasive technique. Within the follow-up period of 6 months, results
      were evaluated seven times. RESULTS: During the whole period significantly
      (p<0.05) better results were observed in the group of operated patients
      concerning shoulder function, Constant score, DASH score, personal satisfaction,
      pain, and cosmetic result. In the second group return to work occurred in less
      than half the time of the first group. CONCLUSION: Intramedullary nailing of mid
      clavicular fractures is a safe and minimally invasive operation technique. Early
      functional and cosmetic results are not worse than results after nonoperative
      treatment with a rucksack bandage.

PMID- 15977007
TI  - [Technique for percutaneous iliosacral screw insertion with conventional C-arm
      radiography].
AB  - BACKGROUND: During percutaneous iliosacral screw fixation, fluoroscopy with a
      conventional C-arm X-ray unit is still the standard procedure for intraoperative
      orientation. Lateral sacral images in combination with the inlet and outlet view
      are always necessary. Nevertheless, the complex pelvic anatomy makes it difficult
      to prevent malpositioning of screws. OPERATIVE TECHNIQUE: Defining the correct
      entry into the bone is the decisive step for ideal screw placement. The better
      this is defined, the larger safety margins will be concerning cortical
      perforation by the screws. In the lateral view, an entry ventral to the sacral
      canal has to be avoided as well as an entry into the cranial half of the first
      sacral vertebra. To improve the surgeon's three-dimensional orientation with the
      help of his personal experience and two-dimensional images, it is recommended to
      place the tip of the screws in the center of the sacrum (in AP view) whenever
      possible. Routinely performed postoperative CT imaging of 24 screws,
      consecutively implanted according to the standards described, revealed no case of
      malpositioning. CONCLUSION: Standard X-ray views in combination with standardized
      aiming of screw entry position and final screw thread position enable the surgeon
      to find the "safe zone" for iliosacral screw insertion and to prevent iliosacral
      screw malpositioning with high accuracy.

PMID- 15977008
TI  - [Treatment results and complications after PFN osteosynthesis].
AB  - Intramedullary implants, such as the proximal femur nails (PFN), are inserted for
      the treatment of per-, inter- and subtrochanteric fractures. The initial
      experiences with these PFN, carried out by AO/ASIF in 1996, have been published.
      PATIENTS AND METHODS: This study makes a systematic examination of the
      complications and clinical treatment results from 133 patients treated at our
      clinic from December 1997-2001 with 139 PFN in per-, inter- and subtrochanteric
      femur fractures. The mean age at the time of surgery was 78.4 years. All
      fractures were classified according to the AO system. The most frequent injuries
      were 31 A2.3 fractures (61.2%). All intraoperative image-converter images and all
      radiographs from the total period of treatment were evaluated retrospectively in
      accordance with 28 criteria. The degree of osteoporosis was estimated using the
      Singh classification. RESULTS: A total of 44 (31.7%) complications arose in 31
      (23.3%) patients. On 11 occasions, hip screw cut-out was observed. Of these, two
      cases involved a Z-effect and one an inverted Z-effect. Two patients suffered a
      femoral neck fracture following removal of the hip screws. There were 38 (27.3%)
      reoperations required with 13 changes in procedure. In autumn 2002, clinical
      follow-up examinations were carried out on 65 (48.9%) patients who were assessed
      according to the Merle d'Aubigne score. A total of 51 (38.3%) patients had died
      at the time of follow-up. Normal ambulation was achieved by 33.8% of patients,
      while 64.6% were free of pain. CONCLUSIONS: The PFN is an appropriate implant in
      cases of per-, inter- and subtrochanteric femur fractures. Anatomical resetting
      and correct implant positioning are the keys to successful osteosynthesis. The
      risk of implant failure is highest in the case of multi-fragmentary per- and
      intertrochanteric fractures in which medial strengthening has been degraded in
      patients aged over 80 years. The clinical results in elderly patients are
      unsatisfactory.

PMID- 15977009
TI  - Severe osteomalacia due to undiagnosed coeliac disease: three case reports of
      Tunisian women.
AB  - We describe three cases of osteomalacia presenting in Tunisian women, all of whom
      had previously-undiagnosed coeliac disease (CD). Direct enquiry revealed an
      important weight loss and a history of diarrhoea in two patients, and a 15-year
      history of anaemia in one patient. Laboratory tests showed severe anaemia in the
      three cases. Reduced calcium was found in two cases, and corrected calcium was
      found in one case. Radiological examination showed fissure in two cases. The
      diagnosis of osteomalacia was made by clinical, biochemical and radiological
      features. Antigliadin, antireticulin, antiendomysial and anti-tissue
      transglutaminase antibodies were all positive in the three cases, and a small
      bowel biopsy confirmed the diagnosis of CD. Treatment with gluten-free diet
      (GFD), supplemental calcium and vitamin D was initiated for the three patients,
      but only one patient complies strictly with the GFD; she showed a marked
      resolution of her symptoms.

PMID- 15977010
TI  - Impairment measures in rheumatic disorders for rehabilitation medicine and allied
      health care: a systematic review.
AB  - The objective of this study is to provide a critical overview of available
      instruments to assess impairments in patients with rheumatic disorders, and to
      recommend reliable and valid instruments for use in allied health care and
      rehabilitation medicine. A computer-aided literature search (1982-2004) in
      several databases was performed to identify studies focusing on the clinimetric
      properties of instruments designed to assess impairments in function in patients
      with rheumatic disorders. Data on intra-rater reliability, inter-rater
      reliability and construct validity were extracted in a standardized way. Explicit
      criteria were applied for reliability and validity. RESULTS: The search
      identified a total of 49 instruments to assess impairments in functions in
      patients with rheumatic disorders; 19 met the criteria for reliability, 22 met
      the criteria for validity, and 11 out of the 49 appeared to meet the criteria for
      both reliability and validity. In summary, evidence of both reliability and
      validity was only found for 11 out of 49 instruments for the assessment of
      impairments in patients with rheumatic disorders. Only a limited number of the
      identified instruments for the assessment of impairments is both reliable and
      valid. Allied health care professionals should be cautious in the selection of
      measurement instruments to assess their patients.

PMID- 15977011
TI  - Heritability of model-derived parameters of beta cell secretion during
      intravenous and oral glucose tolerance tests: a study of twins.
AB  - AIMS/HYPOTHESIS: The genetic architecture of model-derived parameters of beta
      cell function has never been assessed. Therefore, we estimated heritability
      (h(2)) for model-derived phenotypes of insulin secretion in twins. METHODS:
      Thirty-three monozygotic (MZ) and 23 dizygotic (DZ) twin pairs from the Finnish
      Twin Cohort Study underwent an OGTT (plasma glucose/C-peptide at 0, 30, 60, 90
      and 120 min). A subset of the twin pairs (21 MZ/20 DZ) also underwent an IVGTT
      (frequent sampling of plasma glucose/insulin from 0 to 60 min) followed by a 160
      min euglycaemic-hyperinsulinaemic clamp (45 mU.min(-1).m(-2)). Mathematical
      modelling was applied to the IVGTT and the OGTT to assess first-phase (readily
      releasable insulin [RRI]) and second-phase (sigma) secretion (IVGTT), and a
      global index of beta cell performance (OGTT beta index). Intraclass correlation
      coefficients and genetic and non-genetic components for trait variances were
      computed to assess the h(2) of model-derived parameters. RESULTS: The intraclass
      correlation coefficients in MZ twins were 0.78 for RRI, 0.67 for sigma and 0.57
      for OGTT beta index. In DZ twins the correlation coefficients were 0.23, 0.32 and
      0.42, respectively. Using the most parsimonious model for each trait, the h(2)-
      the proportion of variance accounted for by genetic factors--was 76% (95% CI: 53
      88%) for RRI, 28% (34-80%) for sigma and 53% (26-72%) for OGTT beta index.
      CONCLUSIONS/INTERPRETATION: Our findings demonstrate that model-derived
      parameters of insulin secretion have a substantial genetic component and may be
      used in the search for genetic determinants of beta cell function in humans.

PMID- 15977012
TI  - Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii
      rat.
AB  - AIMS/HYPOTHESIS: The spontaneously diabetic Torii (SDT) rat has recently been
      established as a model of type 2 human diabetes mellitus. Male SDT rats develop
      severe diabetic ocular complications. This study investigated the nature of the
      ocular complications in this model and addressed the question of whether the SDT
      rat is a good model of human proliferative diabetic retinopathy. METHODS: Male
      SDT rats aged 50 weeks were studied for a period of 8 months. Under deep
      anaesthesia, one eye of each animal was enucleated following perfusion with
      fluorescein dextran and a retinal flat mount was prepared to study vascular
      structure. The other eye was enucleated and investigated histologically by
      haematoxylin-eosin and azan staining and by immunohistochemistry using antibodies
      against vascular endothelium (Griffonia simplicifolia isolectin B4 antibody) and
      vascular endothelial growth factor (VEGF). RESULTS: From the vascular structure
      study, 17 of 32 rats (53%) showed proliferative retinopathy without vascular non
      perfusion. The histological study revealed traction retinal folds in rats with
      proliferative retinopathy. Azan staining showed some proliferative matrix in rats
      with normal retinal structure and those with proliferative retinopathy compared
      with normoglycaemic controls. Staining with Griffonia simplicifolia isolectin B4
      antibody showed no specific vascular changes in any of the rats, while VEGF
      staining revealed higher immunoreactivity in the retina of rats with normal
      retinal structure and those with proliferative retinopathy, but only low
      immunoreactivity in the control animals. CONCLUSIONS/INTERPRETATION: There appear
      to be differences between the SDT rat model of diabetic retinopathy and human
      proliferative diabetic retinopathy, as the SDT rat develops retinal
      neovascularisation without retinal ischaemia. This very unique display of ocular
      neovascularisation may be caused by increased expression of VEGF.

PMID- 15977014
TI  - Bilateral congenital diaphragmatic hernia.
AB  - Bilateral congenital diaphragmatic hernia (CDH) is a rare condition, with the
      literature suggesting a bleak prognosis. We describe a case of bilateral CDH
      that, despite confirming the challenges of diagnosis, demonstrates that the
      condition can have a favourable outcome.

PMID- 15977013
TI  - [Cheilitis granulomatosa Melkersson-Rosenthal syndrome].
AB  - Melkersson-Rosenthal syndrome is a rare disorder characterized by a triad of
      recurrent orofacial swelling, recurrent paralysis of the facial nerve and lingua
      plicata. The complete triad only occurs in 25% of MRS cases. Monosymptomatic or
      oligosymptomatic variants are more frequent; other findings include granulomas in
      other facial sites, regional lymphadenopathy, fever, psychotic disorders and
      hyperplastic gingivitis are associated with MRS. This can be a diagnostic
      challenge. The etiology and pathogenesis of MRS are unknown. Corticosteroids or
      clofazimine appear the best therapeutic options.

PMID- 15977015
TI  - Strangulated low Spigelian hernia in children: report of two cases.
AB  - Low Spigelian hernia (LSH) in children is considered an extreme surgical rarity.
      This clinically deceptive hernia is difficult to diagnose preoperatively and has
      a real risk of strangulation. Strangulated LSH may be misdiagnosed as
      strangulated inguinal hernia. Early recognition and timely surgical repair are
      important to avoid strangulation.

PMID- 15977016
TI  - Complex presentation of intussusception in childhood.
AB  - The simultaneous occurrence of intussusception and volvulus in the paediatric age
      group is rare. We report the case of a volvulus of an ileoileal intussusception
      in an 8-year-old boy. This is the first time that computerised tomography (CT)
      images of a volvulus of an ileoileal intussusception have been published, and
      they clearly demonstrate both pathologies. This case highlights the use of CT in
      determining the nature of an abdominal mass and demonstrates how helpful it can
      be in diagnosing the cause of small bowel obstruction in children.

PMID- 15977017
TI  - Caudal regression syndrome--case report and review of literature.
AB  - Caudal regression syndrome is a rare disorder of distal spinal segments affecting
      the development of the spinal cord, with attendant sequelae. Intelligence is
      preserved. The exact etiology is elusive, though maternal diabetes, genetic
      factors, and hypoperfusion might play roles. Recently, the role of teratogens has
      been studied in animal models. Treatment is difficult, multidisciplinary, and
      largely supportive. Lower limb deformities with sensory and motor loss and
      neurogenic bladder call for intensive and long-term attention.

PMID- 15977018
TI  - [First experience with a critical incident reporting system in surgery].
AB  - Systems that record critical incidents were initially developed for aeronautics
      and are being increasingly applied in medicine. The objective is to detect
      problems inherent to systems and system errors before they lead to complications
      or do harm to patients. We report our preliminary experience with a critical
      incident reporting system (CIRS). Since February 1 2001, all employees of our
      surgical department have been able to report incidents, anonymously or candidly,
      to a central board using a standardized documentation form. The results are
      presented at monthly internal quality meetings, where two to three crucial
      incidences are thoroughly discussed. New information is communicated and put into
      practice as quickly as possible. A total of 424 incidents were reported from
      February 1, 2001 to December 31, 2003. Reversible damages, some of which resulted
      in prolonged hospitalization, were consequential to 22% of the cases. Thirteen
      percent were classified as "near miss" (almost incidents), whereas 65% had no
      consequences for patients. As expected, doctors and nurses were most frequently
      involved, as 36% of the reported incidents occurred in connection with the
      prescription and administration of medication. In particular, the near miss
      category revealed system errors which in 85% of cases had immediate consequences
      for therapeutic procedures. Based on our initial experiences, working with CIRS
      may be evaluated as positive. The open discussion of incidents and errors also
      revealed minor but often significant system errors, which resulted in alteration
      of our internal proceedings and thus improved the quality and safety of
      treatment.

PMID- 15977019
TI  - Acquired uterine vascular malformations: radiological and clinical outcome after
      transcatheter embolotherapy.
AB  - The purpose of this retrospective study is to assess the radiological and
      clinical outcome of transcatheter embolization of acquired uterine vascular
      malformations in patients presenting with secondary postpartum or postabortion
      vaginal hemorrhage. In a cohort of 17 patients (mean age: 29.7 years; standard
      deviation: 4.23; range: 25-38 years) 18 embolization procedures were performed.
      Angiography demonstrated a uterine parenchymal hyperemia with normal drainage
      into the large pelvic veins ("low-flow uterine vascular malformation") in 83%
      (n=15) or a direct arteriovenous fistula ("high-flow uterine vascular
      malformation") in 17% (n=3). Clinically, in all patients the bleeding stopped
      after embolization but in 1 patient early recurrence of hemorrhage occurred and
      was treated by hysterectomy. Pathological analysis revealed a choriocarcinoma.
      During follow-up (mean time period: 18.8 months; range: 1-36 months) 6 patients
      became pregnant and delivered a healthy child. Transcatheter embolization of the
      uterine arteries, using microparticles, is safe and highly effective in the
      treatment of a bleeding acquired uterine vascular malformation. In case of
      clinical failure, an underlying neoplastic disease should be considered. Future
      pregnancy is still possible after embolization.

PMID- 15977020
TI  - Opposite-direction bilateral fracture dislocation of the shoulders after an
      electric shock.
AB  - Injuries after an electric shock, such as dermal burns, motor and sensory nerve
      deficits, fractures and dislocations, are reported in the literature. Posterior
      dislocation of the shoulder after electric-shock is the common musculoskeletal
      injury. Bilateral dislocation, either anterior or posterior, is rarely seen and
      reported. We report a case of bilateral shoulder fracture dislocation in opposite
      directions following an electric-shock and discuss the mechanism, the diagnosis
      and the treatment.

PMID- 15977021
TI  - Control of severe hemorrhage using C-clamp and arterial embolization in
      hemodynamically unstable patients with pelvic ring disruption.
AB  - INTRODUCTION: Hemorrhage is the leading cause of death in patients with a pelvic
      fracture. The majority of blood loss derives from injured retroperitoneal veins
      and broad cancellous bone surfaces. The emergency management of multiply injured
      patients with pelvic ring disruption and severe hemorrhage remains controversial.
      Although it is well accepted that the displaced pelvic ring injury must be
      rapidly reduced and stabilized, the methods by which control of hemorrhagic shock
      is achieved remain under discussion. It has been proposed to exclusively use
      external pelvic ring stabilization for control of hemorrhage by producing a
      'tamponade effect' of the pelvis. However, the frequency of clinically important
      arterial bleeding after external fixation of the pelvic ring remains unclear. We
      therefore undertook this retrospective review to attempt to answer this one
      important question: How frequently is arterial embolization necessary to control
      hemorrhage and restore hemodynamic stability after external pelvic ring fixation?
      MATERIALS AND METHODS: We performed a retrospective review of 55 consecutive
      patients who presented with unstable types B and C pelvic ring fractures. Those
      patients designated as being in hemorrhagic shock (defined as a systolic blood
      pressure less than 90 mmHg after receiving 2 L of intravenous crystalloid) were
      treated by application of the pelvic C-clamp. Patients who remained in
      hemorrhagic shock, or were determined to be in severe shock (defined as mandatory
      catecholamines or more than 12 blood transfusions over 2 h), underwent
      therapeutic angiography within 24 h in order to control bleeding. RESULTS:
      Fourteen patients were identified as being hemodynamically unstable (ISS 30.1 +/-
      11.3 points) and were treated with a C-clamp. In those patients with persistent
      hemodynamic instability, arterial embolization was performed. After C-clamp
      application, 5 of 14 patients required therapeutic angiography to control
      bleeding. Two patients died, one from multiple sources of bleeding and the other
      from an open pelvic fracture (total mortality 2/14, 14%). CONCLUSIONS: Although
      the C-clamp is effective in controlling hemorrhage, one must be aware of the need
      for arterial embolization to restore hemodynamic stability in a select subgroup
      of patients.

PMID- 15977022
TI  - The muscular branching patterns of the ulnar nerve to the flexor carpi ulnaris
      and flexor digitorum profundus muscles.
AB  - The branching pattern of the ulnar nerve in the forearm is of great importance in
      anterior transposition of the ulnar nerve for decompression after neuropathy of
      cubital tunnel syndrom and malformations resulting from distal end fractures of
      the humerus. In this study, 37 formalin-fixed forearms were used to demonstrate
      the muscular branching patterns from the main ulnar nerve to the flexor carpi
      ulnaris muscle (FCU) and ulnar part of the flexor digitorum profundus muscle
      (FDP). Eight branching patterns were found and classified into four groups
      according to the number of the muscular branches leaving the main ulnar nerve.
      Two (Group I) and three (Group II) branches left the main ulnar nerve in 18 and
      17 forearms respectively. The remaining two specimens had four (Group III) and
      five (Group IV) branches each. Usually one or two branches were associated with
      the innervation of the FCU. However, in 2 cases, three and in one, four branches
      to FCU were observed. The FDP received a single branch in all cases, except in
      four, all of which had two branches. In six forearms, a common trunk was observed
      arising from the ulnar nerve to supply the FCU and FDP. The distribution of the
      muscular branches to the revealed muscles was outlined in figures and the
      distance of the origin of these branches from the interepicondylar line was
      measured in millimeters. The first muscular branch leaving the main ulnar nerve
      was the FCU-branch in all specimens. The terminal muscular branch of the ulnar
      nerve to the forearm muscles arose at the proximal 1/3 of the forearm in all
      specimens. In 7 forearms, Martin-Gruber anastomosis in form of median to ulnar
      was observed.

PMID- 15977023
TI  - Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and
      steroid-resistant nephrotic syndrome of childhood: current status and future
      directions.
AB  - Clinicians are often faced with therapeutic dilemmas and challenges while
      treating children with frequently relapsing steroid-dependent nephrotic syndrome
      (SDNS) and steroid-resistant nephrotic syndrome (SRNS). In the past, children
      with SDNS have been treated with long-term alternate day steroids
      cyclophosphamide, cyclosporine (CSA), chlorambucil, levamisole, and azathioprine.
      The essential aim of these therapies is to maintain remission while limiting
      exposure to steroids. These medications have variable efficacy and undesirable
      toxicity profiles. Recently, mycophenolate mofetil (MMF) has emerged as a new
      therapeutic option for the management of SDNS in a few uncontrolled clinical
      trials. Preliminary data are encouraging. MMF was found to be useful in
      maintaining remission and has a steroid-sparing effect. Clearly, more data are
      needed to further characterize the safety and efficacy of MMF, define adequate
      length of treatment, and optimize drug exposure and monitoring. The management of
      SRNS is primarily aimed at decreasing proteinuria and inducing remission, if
      possible. By doing so, one would aim to preserve renal function. CSA therapy is
      known to be useful in this regard but has undesirable side effects, the most
      concerning being nephrotoxicity. MMF in combination with steroids and angiotensin
      converting enzyme-inhibitor drugs is known to have some efficacy in the
      management of SRNS. These preliminary data have prompted the National Institutes
      of Health to sponsor a multicentric controlled trial to compare the safety and
      efficacy of MMF with that of CSA in the treatment of steroid-resistant focal
      segmental glomerulosclerosis (FSGS). If MMF therapy is found to be efficacious,
      it would help obviate the need for CSA and its associated nephrotoxicity.
      Clearly, MMF has emerged as an important new therapeutic option for the treatment
      of childhood nephrotic syndrome and FSGS. Further data are required to assess
      those conditions most likely to respond.

PMID- 15977025
TI  - Vincristine treatment in steroid-dependent nephrotic syndrome.
AB  - Treatment of children with steroid-dependent nephrotic syndrome (SDNS) continues
      to be a challenge when relapses recur after treatment with cyclophosphamide and
      side effects or non-compliance make steroids and cyclosporin unsatisfactory. We
      treated 12 patients with intravenous vincristine for SDNS in a regime of 1-1.5
      mg/m2 weekly for 4 weeks then monthly for 4 months. Four of the 5 patients in
      relapse when commencing vincristine remitted within 2 doses. Comparing relapse
      frequency in the 12 months before and after vincristine, there was a reduction
      from 4 to 1.5 (p=0.004) relapses per year. Median sustained remission was 5
      months, but 1 frequently relapsing patient remains in remission 4 years after
      vincristine. Vincristine was also successfully used in 1 or 2 doses at weekly
      intervals for subsequent relapses in 5 patients. Side effects were minimal in
      most cases. Abdominal pain occurred in 2 patients who commenced vincristine at
      1.5 mg/m2, but resolved when continued at 1 mg/m2. We felt vincristine had a role
      in a subset of children with challenging SDNS administered as 1 mg/m2 weekly for
      4 weeks then 1.5 mg/m2 monthly for 4 months. Vincristine allowed steroid- and
      cyclosporin-sparing, contributed to long-term remission in some patients, and was
      especially valuable in children with poor compliance with oral medication. Many
      patients expressed a preference for a few doses of vincristine rather than a
      standard course of oral prednisolone or cyclosporin.

PMID- 15977024
TI  - Renal pathology in children with mitochondrial diseases.
AB  - We studied renal involvement in 42 children with mitochondrial diseases (MDs).
      The diagnosis of MD was established by morphological, biochemical, and molecular
      genetic criteria. Renal disease was considered when patients had renal failure,
      nephrotic syndrome, Fanconi's syndrome or any symptomatic renal alteration. Mild
      tubular disorder was established if they had abnormal laboratory findings with no
      apparent clinical symptom. Renal involvement was found in 21 children (50%), of
      whom 8 had an apparent clinical picture and 13 a mild tubular disorder. Five
      patients with renal disease showed Debre-Toni-Fanconi's syndrome, 2 of them with
      decreased glomerular filtration rate (GFR). One case had nephrotic syndrome,
      another one presented decreased GFR, and the last one had a neurogenic bladder
      and bilateral hydronephrosis. Patients with mild renal disease showed tubular
      dysfunction with normal GFR. Renal involvement is frequent and present in about
      half of the children with MD. Thus, studies for evaluating kidney function should
      be performed on children with MD. Conversely, patients with tubulopathy of
      unknown origin or progressive renal disease should be investigated for the
      existence of MD, especially if associated with involvement of other organs or
      tissues. Southern blot analysis to search for large-scale mitochondrial DNA
      (mtDNA) rearrangements should be performed for patients with MD and kidney
      involvement.

PMID- 15977026
TI  - Maturation of malfunctioning kidneys.
AB  - Because loss of functional renal mass is compensated by hyperfiltration of
      remaining tissue, one could hypothesize that a damaged kidney might not have the
      same rate of maturation as the contralateral one. To verify this, maturation was
      evaluated in children with asymmetrical renal function during early life. Twenty
      five children were selected having had 2 (99m)Tc-MAG3 renograms combined with
      (51)Cr-EDTA clearance measurement, enabling estimation of glomerular filtration
      rate (GFR), split renal function (SRF), and single kidney GFR (SKGFR). The first
      test had to be performed before the age of 18 months and SRF on the affected side
      had to be < or =40%. Moreover, GFR had to increase between the 2 tests by > or
      =10 mL(-1) min/1.73 m(2), reflecting maturation due to age. For 18 children SRF
      changed by between -5% and +5%. For 4 children an increase of > or =5% was
      observed whereas for the remaining 3 a decrease of > or =5% occurred. For the
      first 22 kidneys, mean increase of SKGFR was +6.3 mL(-1) min/1.73 m(2)(SD: 6).
      For the 3 kidneys with > or =5% SRF decrease, SKGFR remained unchanged in 2 (+0.3
      and -3 mL min(-1)/1.73 m(2)) and increased in the third patient (+15 mL min(
      1)/1.73 m(2)). In conclusion, renal maturation is comparable in both the
      malfunctioning kidney and the contralateral normal functioning side.

PMID- 15977027
TI  - Growth in adolescent hemodialysis patients: data from the Centers for Medicare &
      Medicaid Services ESRD Clinical Performance Measures Project.
AB  - The Centers for Medicare & Medicaid Services' (CMS) end-stage renal disease
      (ESRD) Clinical Performance Measures (CPM) Project has collected data on all
      adolescent hemodialysis patients since 2000. Thus, by 2002 data were available on
      all adolescents on hemodialysis in the USA for 3 consecutive years. Possible
      associations between clinical parameters and linear growth in this cohort were
      evaluated. Ninety-four adolescents were on hemodialysis for the 3 study years.
      The mean height standard deviation score (ht SDS) fell from -1.97 to -2.36 over
      the 3 study years. Compared with patients with ht SDS > or =-1.88, patients with
      ht SDS <-1.88 in the 2002 study year (n =53) were more likely to be male (66% vs
      44%, p <0.05), on dialysis longer (6.9+/-4.5 years vs 4.1+/-2.3 years, p <0.001),
      and had lower height SDS in the 2000 study year (-2.90+/-1.31 vs -0.772+/-1.10, p
      <0.001). Patients with a ht SDS <-1.88 had a lower mean hemoglobin (11.4+/-1.6
      g/dl vs 12.0+/-1.1 g/dl, p <0.05), but there were no differences in other
      clinical parameters. Among patients with ht SDS <-1.88, 38.8% (n =20) were
      prescribed recombinant human growth hormone (rhGH) in the 2002 study year. There
      were no differences in demographic or clinical parameters between rhGH treated
      and untreated patients. Many adolescents who remain on hemodialysis have poor
      linear growth. Further evaluation is needed to delineate contributory factors and
      the possible underutilization of rhGH.

PMID- 15977029
TI  - Speciation of aluminium in tea infusions by use of SEC and FPLC with ICP-OES and
      ES-MS-MS detection.
AB  - Speciation of Al in tea infusions was studied by size exclusion chromatography
      (SEC) and anion-exchange fast protein liquid chromatography (FPLC). Fractions
      were collected throughout the chromatographic separations and Al was determined
      "off line" by inductively coupled plasma optical emission spectroscopy (ICP-OES).
      Black, green, and red tea samples were investigated. The total concentration of
      Al in tea infusions was determined by ICP-OES and ranged between 0.5 and 4 mg dm(
      3). The pH of tea infusions ranged between 5.3 and 5.5. Data from SEC-ICP-OES
      analysis indicated that 10-35% of total Al in tea infusions was eluted at a
      retention volume corresponding to a molecular mass of approximately 3800 Da. The
      remaining Al was adsorbed on the column resin. The same tea infusions were also
      analysed by anion-exchange FPLC-ICP-OES. It was found experimentally that the
      same percentage of total Al as from the SEC column was eluted at a retention
      volume that corresponded to negatively charged Al-citrate. The remaining Al was
      adsorbed on the column resin. Identification of Al-binding ligands eluting under
      the chromatographic peak was performed by electrospray ionisation tandem mass
      spectrometry (ES-MS-MS) analysis. It was proven that ionic Al species in tea
      infusions (10-35% of the total Al) corresponded to negatively charged Al-citrate.
      The remaining species that was adsorbed on the SEC or FPLC columns was most
      probably bound to phenolic compounds. Speciation of Al in tea with milk or lemon
      was also studied. Results for tea with milk indicated that Al-citrate was not
      transformed and that approximately 60% of total Al was transformed into high
      molecular-mass Al species. This fraction was subjected to sodium dodecyl
      sulfonate polyacryl gel electrophoresis (SDS-PAGE). The results indicated that Al
      was occluded by milk proteins (mostly caseins). When citric acid was added to tea
      infusions the percentage of negatively charged Al-citrate remained either the
      same or increased to 40% of total Al.

PMID- 15977030
TI  - Development of a competitive liposome-based lateral flow assay for the rapid
      detection of the allergenic peanut protein Ara h1.
AB  - A competitive lateral flow assay for detecting the major peanut allergen, Ara h1,
      has been developed. The detector reagents are Ara h1-tagged liposomes, and the
      capture reagents are anti-Ara h1 polyclonal antibodies. Two types of rabbit
      polyclonal antibodies were raised either against the entire Ara h1 molecules
      (anti-Ara h1 Ab) or against an immunodominant epitope on Ara h1 (anti-peptide
      Ab). All of them reacted specifically with Ara h1 in Western Blot against crude
      peanut proteins. Moreover, the anti-Ara h1 Ab was chosen for this assay
      development because of its highest immunoactivity to Ara h1-tagged liposomes in
      the lateral flow assay. The calculated limit of detection (LOD) of this assay is
      0.45 microg mL(-1) of Ara h1 with a dynamic range between 0.1 and 10 microg mL(
      1) of Ara h1 in buffer. Additionally, the visually determined detection range is
      from 1 to 10 microg mL(-1) of Ara h1 in buffer. Results using this assay can be
      obtained within 30 min without the need of sophisticated equipment or techniques;
      therefore, this lateral flow assay has the potential to be a cost-effective,
      fast, simple, and sensitive method for on-site screening of peanut allergens.

PMID- 15977031
TI  - Assay for uric acid level in rat striatum by a reagentless biosensor based on
      functionalized multi-wall carbon nanotubes with tin oxide.
AB  - A novel reagentless amperometric uric acid biosensor based on functionalized
      multi-wall carbon nanotubes (MWCNTs) with tin oxide (SnO2) nanoparticles has been
      developed. This was successfully applied to assay uric acid levels from an in
      vivo microdialysis sampling. Compared with unfunctionalized or traditional
      carboxylic acid (-COOH)-functionalized MWCNTs, the MWCNTs-SnO2 electrode
      exhibited higher electrocatalytic oxidation to uric acid. Here, MWCNTs-SnO2 may
      act as an efficient promoter, and the system exhibited a linear dependence on the
      uric acid concentration over the range from 1.0 x 10(-7) to 5.0 x 10(-4) mol L(
      1). In addition, there was little ascorbic acid interference. The high
      sensitivity of the MWCNTs-SnO2 modified enzyme electrode enabled the monitoring
      of trace levels of uric acid in dialysate samples in rat striatum.

PMID- 15977032
TI  - Chemiluminescence immunoassay for chloramphenicol.
AB  - In recent years, various chemiluminescent clinical immunoassay kits have been
      widely applied to the detection of hormones. However, a kit for chloramphenicol
      (CAP) is often absent from most commercial product lists, even though it is
      important to control the levels of CAP residues in foodstuffs too. Therefore, we
      describe a simple, solid-phase chemiluminescence immunoassay (CLIA) for the
      measurement of CAP in foodstuffs. A rabbit anti-CAP IgG is passively adsorbed
      onto the walls of polypropylene plates. The labeled antigen is horseradish
      peroxidase (HRP) conjugate of CAP. Luminol solution is used as the substrate of
      HRP. The light yield is inversely proportional to the concentration of CAP. The
      method has a similar sensitivity (0.05 ng/ml), specificity, precision, and
      accuracy to a conventional enzyme immunoassay (EIA). The intra-assay and inter
      assay CVs of ten samples were <8% and <20%, respectively, and the analytical
      recovery of the method was 87-100%. The experimental correlation coefficient of
      dilution was found to be 0.999 using milk supernatant as buffer. The detection
      limit for the method was 0.1-10 ng/ml, and it displayed good linearity.

PMID- 15977033
TI  - Characterisation of selenium compounds in rye seedling biomass using 75Se
      labelling/SDS-PAGE separation/gamma-scintillation counting, and HPLC-ICP-MS
      analysis of a range of enzymatic digests.
AB  - In the present study, selenium-enriched plant biomass was investigated to
      evaluate the ability of rye seedlings to take up, and assimilate, inorganic
      selenium. Two different analytical approaches were used. Electrophoretic
      separation (SDS-PAGE) of proteins extracted from 75Se-labelled biomass was used
      to investigate the biotransformation of selenite into organic forms of the
      element. Ion-pair chromatography coupled with ICP-MS detection was chosen for the
      analysis of selenium species, enzymatically extracted from the plant biomass. The
      results of three enzymatic hydrolysis procedures and three sequential enzymatic
      extractions procedures are compared. The most effective single extraction was
      proteolysis (using protease type XIV), giving an overall extraction efficiency of
      48%. However, for combinations of enzymes, the most effective was cellulase
      (Trichoderma viride) followed by sequential extraction of the solid pellet using
      protease type XIV, giving an extraction efficiency of 70%. The complementary data
      from the electrophoretic fractionation of proteins, and the HPLC separation of Se
      species in the proteolytic digests, reveal the existence of large number of
      selenium-containing compounds in the rye seedling plant biomass. The results
      showed the complete biotransformation of inorganic selenium into organic forms
      during germination of the rye seedlings. HPLC-ICP-MS analysis of extracts from
      the plant biomass did not show the presence of selenate or selenite. At the time
      of this study, the lack of suitable organic-MS facilities meant that it was not
      possible to characterise them fully. However, the data does show that a
      combination of different enzymes, rather than just the commonly-used protease,
      should be considered when developing an extraction strategy for selenium in
      different food types to those already reported in the literature.

PMID- 15977035
TI  - Enzyme digestion to isolate and culture human scalp dermal papilla cells: a more
      efficient method.
AB  - In this study, we show a more efficient method for isolation and cultivation of
      dermal papilla cells from hair follicles of human scalp skin. The dermal
      partments of low hair follicles were pulled out from cutaneous fat and the bulb
      epithelium was teased out from the fibrous sheath with attached dermal papilla by
      applying gentle pressure with the tip of an occal forceps. When these fibrous
      sheaths were entirely digested into isolated cells by collagenase D but the
      dermal papillae were justly to be digested, collagenase D was discarded and the
      dermal papillae were isolated completely out from the resuspension solution by
      repeated low-speed centrifugation and transferred to another dish for free
      floating culture. This procedure markedly simplifies the steps of isolated dermal
      papilla operation and relieves the laborious tension. Furthermore, dermal
      papillae could be isolated on a large-scale and remained intact. After
      collagenase digestion, the dermal papillae showed very high adherent rate and
      quicker growth than that of microdissection, which suggests that the definition
      factor of dermal papilla cell migration was relaxed and some structure had been
      activated or exposed. The cells exhibited a multi-layer forming property and
      spread-out growth style. They showed positive with alcian blue, with toluidine
      blue O for different gradient pH and PAS, which was similar to the staining
      results of in situ dermal papilla. It suggests that the culture papilla cells
      still synthesize and excrete neutral and acid mucopolysaccharides. Our results
      demonstrate that the papilla cells in culture condition still remain the ability
      to synthesize the specific extracellular matrix components of in situ dermal
      papilla, which supports the concept that the dermal papilla cell, a highly
      specialized fibroblast, especially is involved in hair growth regulation.

PMID- 15977036
TI  - The potential impact of implementing a system of generic substitution on the
      community drug schemes in Ireland.
AB  - This study estimated the potential savings in Ireland in 2003 if a system of
      generic substitution were introduced, under the two main Community Drug Schemes
      (General Medical Services, GMS, and Drugs Payment, DP). The GMS and DP schemes
      accounted for 82% of state expenditure on the Community Drug Schemes in 2003.
      Twenty one per cent of prescription items on the GMS scheme and 23% of items on
      the DP scheme were dispensed as a proprietary preparation when a generic
      equivalent was available. Substitution of the cheapest generic equivalent
      preparations of the top 30 drugs by expenditure in each scheme would result in
      estimated annual savings of <euro>12.7 million on the GMS and <euro>9.1 million
      on the DP scheme. Potential savings if the most expensive generic drugs were
      dispensed would be in the region of <euro>9.0 million on the GMS and <euro>6.4
      million on the DP scheme. Comparison of these results with a similar analysis of
      2001 data illustrates the potential for an increase in savings over time.

PMID- 15977034
TI  - Investigation of multidrug resistance in cultured human renal cell carcinoma
      cells by 31P-NMR spectroscopy and treatment survival assays.
AB  - KTCTL-26 and KTCTL-2 are renal cell carcinoma (RCC) lines with high and low
      expression of P-170 glycoprotein, respectively. Inherent differences between the
      two cell lines in terms of phosphate metabolites and growth characteristics in
      culture were examined for possible association with multidrug resistance (MDR).
      Differences in response to drug treatment were investigated for 40 h incubations
      with various doses of vinblastine (VBL) alone or as cotreatments with various
      concentrations of the calcium antagonist diltiazem (DIL) and/or interferon-alpha
      (IFN-alpha). Treatment effects were quantitated using the MTT survival assay and
      31P magnetic resonance spectroscopy (MRS) to determine phosphate metabolite
      profiles in intact cells. KTCTL-2 and KTCTL-26 cells exhibited significant
      inherent differences in phosphocholine, glycerophosphocholine,
      glycerophosphoethanolamine, and phosphocreatine levels. KTCTL-26 cells were more
      sensitive than KTCTL-2 to 0.011 mircroM VBL alone (87% vs. 102% survival) or to
      0.011 microM BL + 10 microM DIL (55% vs. 80% survival). The latter treatment
      resulted in a significant decrease in the ratio of phosphocholine to
      glycerophosphocholine in KTCTL-26 cells but no significant changes in phosphate
      metabolites in KTCTL-2 cells. Metabolomic 31P MRS detects different metabolite
      profiles for RCC cell lines with different MDR phenotypes and may be useful for
      noninvasive characterization of tumors in a clinical setting.

PMID- 15977037
TI  - A deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene produces the
      phenotype of inclusion body beta-thalassemia.
AB  - Dominant inherited beta-thalassemias describe those beta-thalassemia variants
      that result in a thalassemia intermediate phenotype in individuals who have
      inherited only a single copy of the abnormal beta gene. This form of thalassemia
      is characterized by moderately severe anemia with jaundice and splenomegaly; it
      is also characterized by the presence of inclusion bodies in the red blood cell
      precursors and has, therefore, previously been referred to as inclusion body beta
      thalassemia. We describe a case of inclusion body beta-thalassemia in a 51-year
      old Spanish male caused by a deletion of 11 bp (CD 131-134) in exon 3 of the beta
      globin gene. The deletion of 11 bp in exon 3 of the beta-globin chain is
      predicted to produce an anomalous chain of 134 amino acids instead of the normal
      146 with an extremely altered amino acid sequence from residues 131-134. Although
      this shortened variant would lead to a missing H helix, which is involved in
      alpha1beta1 contact and alpha1beta2 subunit interactions, the variant chain can
      still be bound to the heme group and acquire a secondary structure that is not
      suitable for the formation of stable dimers or tetramers and also less
      susceptible to proteolytic degradation. This is the first report of such a beta
      thalassemia mutation.

PMID- 15977038
TI  - [Effect compartment equilibration and time-to-peak effect. Importance of a
      pharmacokinetic-pharmacodynamic principle for the daily clinical practice].
AB  - Contrary to the situation in "classical" clinical pharmacology, non-steady state
      phenomena play a fundamental role for clinical pharmacology in anesthesia. Their
      understanding is of tantamount importance for the safe and efficient application
      of drugs relevant to anesthesia. Concepts like optimised target-controlled
      infusion (TCI), effect compartment targeting and the small margin of error
      tolerable during maintained spontaneous ventilation, force the anesthesiologist
      to acquire a firm understanding of the difference between the concentration time
      course at the effect side vs. time course of the plasma concentration. The
      underlying concepts, their application for the rational use of muscle relaxants,
      propofol with TCI systems, volatile anaesthetics and opioids will be discussed.

PMID- 15977039
TI  - [Laser-based quality assurance for robot-assisted milling at the base of the
      skull].
AB  - BACKGROUND: Implanting active hearing devices in the lateral base of the skull
      requires high-precision, secure fixation of the electromagnetic transducer and
      long-life anchorage using osteosynthetic fixation plates referred to as mountain
      brackets. Nonlinear distortion in the acoustic signal path and consecutive
      implant loosening can only be avoided by exact osseous milling to create the
      necessary cavity bed while avoiding excessive milling. Robot technology is ideal
      for high-precision milling. However, safety measures are necessary in order to
      prevent errors from occurring during the reduction process. Ideally, a robot
      should be guided by a navigation system. However, robotic systems so far
      available do not yet have an integrated global navigation system. MATERIALS AND
      METHODS: We used an animal model under laboratory conditions to examine the
      extent to which the semiautomatic ROBIN assistant system developed could be
      expected to increase osseous milling accuracy before implanting active electronic
      hearing devices into the recipient tissue in the cranium. An existing prototype
      system for robot-assisted skull base surgery was equipped with laser sensors for
      geometric measurement of the operation site. The three-dimensional measurement
      data was compared with CT simulation data before, during, and after the robot
      assisted operation. The experiments were conducted on test objects as well as on
      animal models. RESULTS: Under ideal conditions, the operation site could be
      measured at a spatial resolution of better than 0.02 mm in each dimension.
      However, reflections and impurities in the operation site from bleeding and
      rinsing fluids did have a considerable effect on data collection, necessitating
      specialised registering procedures. Using an error-tolerant procedure
      specifically developed, the effective registering error could be kept under 0.3
      mm. After milling, the resulting shape matched the intended form at an accuracy
      level of 0.8 mm. CONCLUSION: The results show that robot systems can reach the
      accuracy required for reliable microsurgery on the cranial base. High-resolution
      laser-based geometric measurement of the operation site enables head registration
      without additional artificial landmarks. During the navigated operation, the
      procedure can be used to ensure that the resulting cavity matches the intended
      shape as determined in the preoperative planning phase. This will enable
      quantitative analysis of, and improvement in the quality of robot-assisted
      surgery in the future.

PMID- 15977040
TI  - Phenylalanine ammonia-lyase modified with polyethylene glycol: potential
      therapeutic agent for phenylketonuria.
AB  - Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by the
      defects in the phenylalanine hydroxylase (PAH) gene. Individuals homozygous for
      defective PAH alleles show elevated levels of systemic phenylalanine and should
      be under strict dietary control to reduce the risk of neuronal damage associated
      with high levels of plasma phenylalanine. Researchers predict that plant
      phenylalanine ammonia-lyase (PAL), which converts phenylalanine to nontoxic t
      cinnamic acid, will be an effective therapeutic enzyme for the treatment of PKU.
      The problems of this potential enzyme therapy have been the low stability in the
      circulation and the antigenicity of the plant enzyme. Recombinant PAL originated
      from parsley (Petroselinum crispum) chemically conjugated with activated PEG2
      [2,4-bis(O-methoxypolyethyleneglycol)-6-chloro-s-triazine] showed greatly
      enhanced stability in the circulation and was effective in reducing the plasma
      concentration of phenylalanine in the circulation of mice. PEG-PAL conjugate will
      be an effective therapeutic enzyme for the treatment of PKU.

PMID- 15977041
TI  - L-NAME administration prevents the inhibition of nucleotide hydrolysis by rat
      blood serum subjected to hyperargininemia.
AB  - The main objective of the present study was to evaluate the in vivo and in vitro
      effect of Arg on serum nucleotide hydrolysis. The action of Nomega-nitro-L
      arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the
      effects produced by Arg was also examined. Sixty-day-old rats were treated with a
      single or a triple (with an interval of 1 h between each injection)
      intraperitoneal injection of saline (group I), Arg (0.8 g/kg) (group II), L-NAME
      (2.0 mg/kg or 20 mg/kg) (group III) or Arg (0.8 g/kg) plus L-NAME (2.0 mg/kg or
      20 mg/kg) (group IV) and were killed 1 h later. The present results show that a
      triple Arg administration decreased ATP, ADP and AMP hydrolysis. Simultaneous
      injection of L-NAME (20 mg/kg) prevented such effects. Arg in vitro did not alter
      nucleotide hydrolysis. It is suggested that in vivo Arg administration reduces
      nucleotide hydrolysis in rat serum, probably through nitric oxide or/and
      peroxynitrite formation.

PMID- 15977043
TI  - Characteristics of natural mentoring relationships and adolescent adjustment:
      evidence from a national study.
AB  - This research investigated characteristics of natural mentoring relationships
      (mentor role, frequency of contact, closeness, duration) as predictors of
      adjustment outcomes among older adolescents and young adults (N = 2,053) in the
      Add Health study. Outcomes were assessed in the domains of education/work,
      problem behavior, psychological well-being, and physical health. Mentoring
      relationships with persons in roles outside of the family predicted greater
      likelihood of favorable outcomes in all domains except psychological well-being,
      relative to mentoring relationships with family members. Greater reported
      closeness in relationships was predictive of several favorable outcomes,
      particularly those in the domain of psychological well-being. These findings
      indicate that strategies to promote mentoring of adolescents may be more
      effective if particular categories of adults are targeted and an effort is made
      to cultivate relationships with strong emotional bonds. Editors' Strategic
      Implications: These data suggest that the cultivation of natural (especially non
      familial) mentoring relationships during adolescence may be a promising strategy
      for prevention and health promotion. This study is impressive due to its large,
      nationally representative sample, the examination of relationship characteristics
      and multiple mentors, and the links to a variety of outcomes (controlling for
      earlier functioning). School officials and mentoring programs must consider how
      to capitalize on - and promote - naturally occurring mentor relationships.

PMID- 15977044
TI  - Developmental mentoring match characteristics: correspondence between mentors'
      and mentees' assessments of relationship quality.
AB  - Understanding the factors that contribute to high-quality mentoring relationships
      is critical to developing and sustaining effective mentoring programs. In study
      1, sixty-three adolescent mentors, from two high schools, were surveyed four to
      six weeks after being matched with elementary-age mentees. Hierarchical
      regression models revealed that mentees' academic and behavioral risk status,
      parental involvement, and program quality all explained variance in mentor
      perceived relationship quality, but none remained significant predictors after
      mentors' self-efficacy, motivations for self-enhancement, and assessments of
      their mentees' support seeking behaviors were accounted for. Study 2 cross
      validates the regression model in study 1 and examines the concurrent validity
      and predictive validity of a measure of mentoring match characteristics using mid
      year and end-of-year assessments from mentees and mentors. Editors' Strategic
      Implications: The focus on mentors' initial impressions of their mentees and the
      relationship represents a novel contribution to the study of relationship
      formation and persistence. The authors provide a promising strategy - and
      descriptions of specific measures - to help programs study relationships that
      endure or terminate. Coordinators will benefit from the knowledge that if mentors
      feel efficacious and if the mentoring relationship is strong, mentors are more
      likely to persist.

PMID- 15977045
TI  - Perceived autonomy and relatedness as moderating the impact of teacher-student
      mentoring relationships on student academic adjustment.
AB  - This study examined the impact of a 10-hour teacher-student mentoring
      relationship on the academic adjustment of at-risk college students. A quasi
      experimental design involving a comparison group (NM: students with No Mentor), a
      High Relatedness/Autonomy group (HR/HA: students who perceived high levels of
      relatedness and autonomy during the mentoring process) and a Low
      Relatedness/Autonomy group (LR/LA: students who perceived low levels of
      relatedness and autonomy during the mentoring process) was used for that purpose.
      Academic adjustment and performance were assessed before (Time 1) and five months
      after involvement in mentoring (Time 3) for all students. Perceived relatedness
      and autonomy were assessed after the last mentoring meeting (Time 2) for students
      involved in mentoring relationships only. Results indicated better social
      adjustment and institutional attachment in college for the HR students than for
      the LR and NM students, even after controlling for initial adjustment,
      performance and social network dispositions. In addition, the LR and LA students
      presented lower academic and emotional adjustment in college and lower academic
      performance than NM, HR, and HA students. The potential positive and negative
      impacts of mentoring relationships are discussed in light of autonomy and
      relatedness processes. Editors' Strategic Implications: Especially valuable is
      the articulation of why mentoring might be expected to affect social and academic
      adjustment outcomes via its effects on the development of autonomy and
      relatedness. Application of attachment theory and measurement to the study of
      mentoring is a strategy that shows promise.

PMID- 15977046
TI  - YouthFriends: outcomes from a school-based mentoring program.
AB  - This evaluation explores the effectiveness of school-based mentoring as a
      universal prevention strategy. The impact of mentoring on students displaying
      risk factors is also addressed. The evaluation of YouthFriends, a school-based
      mentoring program, employed a pretest-posttest control group design. Students (n
      = 170) across five school districts provided data on eight dependent variables.
      At posttest, there was a statistically significant difference favoring
      YouthFriends over controls on sense of school membership. In addition, for
      students who had low scores at baseline, results indicated a statistically
      significant improvement unique to YouthFriends on community connectedness and
      goal-setting. Analyses of students' academic performance also indicated a
      positive effect for those YouthFriends who had low grades at baseline. Editors'
      Strategic Implications: Important lessons are provided for school administrators
      and mentoring program staff and evaluators. As a universal prevention program,
      school-based mentoring may produce few (and small) short-term effects. A greater
      understanding of the effects of dosage and quality of the mentoring is needed as
      we seek to evaluate the efficacy of school-based mentoring across a variety of
      student risk levels.

PMID- 15977047
TI  - Promoting successful youth mentoring relationships: a preliminary screening
      questionnaire.
AB  - Youth mentoring programs are an increasingly popular intervention, and although
      successful mentoring relationships can promote a range of positive developmental
      outcomes, relationships that fail can lead to decrements in a youth's functioning
      and self-esteem. The present research develops and validates a youth mentoring
      relationship quality inventory, based on data from a national evaluation of Big
      Brothers Big Sisters (BBBS) mentoring programs (N = 347 youth). This tool can be
      administered to adolescents who have been assigned mentors in order to assess the
      quality of the relationship as it is forming and to identify dyads that may need
      additional support before those relationships fail. Implications of such a tool
      for mentoring interventions and research are discussed. Editors' Strategic
      Implications: Reliability and validity data are presented for a measure of
      youth's perceptions of the quality of their mentoring relationship. This measure
      shows promise as a tool for research and evaluation of a wide array of mentoring
      programs due to its brevity, demonstrated psychometrics, and straightforward
      focus on the mentoring relationship.

PMID- 15977048
TI  - A systemic model of the youth mentoring intervention.
AB  - Conceptual and empirical work on youth mentoring naturally tends to focus on the
      relationship between mentor and child. However, the parent/guardian and agency
      caseworker also may contribute to the success or failure of the mentoring
      intervention, and program effects may be partially mediated by the child's
      interactions with these individuals. This article presents a systemic model of
      mentoring depicting the interdependent network of relationships established
      between mentor, child, parent/guardian, and caseworker against the backdrop of
      agency policies and procedures. Numerous examples illustrate pathways of
      influence and patterns of communication in the context of this more holistic
      model of mentoring. Editors' Strategic Implications: Drawing upon ecological and
      systems theories, the author provides a promising conceptual model that focuses
      on patterns of interpersonal exchange among several key individuals (but not the
      only possible ones). This model reminds researchers and practitioners that
      mentoring resides within a mutually reinforcing (or inhibiting) network of other
      relationships. This systemic thinking has implications for child welfare agency
      policies and practices.

PMID- 15977049
TI  - Mentoring at-risk preschoolers: lessons from the A.R.Y.A. Project.
AB  - The A.R.Y.A. ("Advancement of Resilience at a Young Age") Project addresses at
      risk 4-year-old kindergarten children in a trial to promote their resilience. The
      project is implemented by mentors, who strove to establish in the children an
      internal assumption that it is worthwhile to pursue a way to change unpleasant
      events, even if previous efforts were fruitless. Following a short description of
      the A.R.Y.A. project, several lessons on mentoring preschoolers are delineated
      and discussed.

PMID- 15977051
TI  - The Starting Well Health Demonstration Project.
AB  - This paper describes the initial development and implementation of the Starting
      Well Health Demonstration Project, Scotland's national child health demonstration
      project. The Project, initially launched in 2000, aims to demonstrate that child
      health can be improved by a program of activities that both supports families and
      provides them with access to enhanced community-based resources. Early process
      outcomes will be presented and policy implications arising out of the Project to
      date will be explored.

PMID- 15977052
TI  - Evaluating "Starting Well", the Scottish national demonstration project for child
      health: outcomes at six months.
AB  - This paper presents early findings from the evaluation of Starting Well, an
      intensive home visiting program aimed at improving the health of pre-school
      children in disadvantaged areas of Glasgow, Scotland. Using a quasi-experimental
      design, detailed survey, observation and interview data were collected on a
      cohort of 213 intervention and 146 comparison families over the first six months
      of the child's life. After controlling for relevant background characteristics,
      multivariate regression analysis revealed higher child dental registration rates
      and lower rates of maternal depressive symptoms in the intervention cohort.
      Findings are interpreted as positive evidence of early program impact.
      Implications, limitations and future plans for analysis are discussed. EDITORS'
      STRATEGIC IMPLICATIONS: Starting Well draws on elements of an Australian parent
      education program and an American home visitation model. The authors demonstrate
      how the program implementation, research questions, and measurement are designed
      to fit their Glasgow population and the Scottish public health system. Their
      quasi-experimental data suggest that this primary prevention program is a
      promising strategy for improving maternal and child health outcomes.

PMID- 15977053
TI  - Translating a research intervention into community practice: the nurse family
      partnership.
AB  - Public policy initiatives have begun to recommend that interventions have strong
      evidence of effectiveness before there is expenditure of restrained public funds.
      The Nurse Family Partnership (NFP), a home visiting program for low-income
      parents expecting their first child, has been identified as a preventive
      intervention program that meets high evidentiary standards based on results from
      three randomized trials. Strategies used to promote successful translation of the
      research intervention into clinical practice, findings from the evaluation of the
      replication of the NFP in 22 states, and challenges experienced in moving a
      research program to practice are discussed. EDITORS' STRATEGIC IMPLICATIONS:
      Policymakers, community public health officials, and researchers planning to
      disseminate their prevention programs will find many lessons in this example of
      bringing a model program (i.e., a prevention strategy that works) up to scale.
      Although results at replication sites are somewhat weaker than at model sites,
      the consistent positive outcomes are a testimony to the strength of the NFP model
      and the fidelity of its implementation across sites.

PMID- 15977054
TI  - Early childhood intervention programs in the US: recent advances and future
      recommendations.
AB  - Recent scientific reviews, long term outcome studies, and effectiveness trials of
      early childhood intervention programs in the US have important lessons for the
      future of these interventions in the US and internationally. Programs should (1)
      employ more center-based or mixed center-based and home visiting models, (2)
      monitor standards of quality, (3) become more family focused and culturally
      competent, and (4) broaden the focus of their evaluations. If these
      recommendations are followed then we will be in a better position to get the best
      return on our investments in early childhood.

PMID- 15977056
TI  - Structural differences in the inner part of photosystem II between higher plants
      and cyanobacteria.
AB  - A detailed comparison of key components in the Photosystem II complexes of higher
      plants and cyanobacteria was carried out. While the two complexes are overall
      very similar, significant differences exist in the relative orientation of
      individual components relative to one another. We compared a three-dimensional
      map of the inner part of plant PS II at 8 A resolution, and a 5.5 A projection
      map of the same complex determined by electron crystallography, to the recent 3.5
      3.8 A X-ray structures of cyanobacterial complexes. The largest differences were
      found in the rotational alignment of the cyt b(;)559 subcomplex, and of the CP47
      core antenna with respect to the D1/D2 reaction centre. Within the D1/D2
      proteins, there are clear differences between plants and cyanobacteria at the
      stromal ends of membrane-spanning helices, even though these proteins are highly
      homologous. Notwithstanding these differences in the protein scaffold, the
      distances between the critical photosynthetic pigment cofactors seem to be
      precisely conserved. The different protein arrangements in the two complexes may
      reflect an adaptation to the two very different antenna systems, membrane
      extrinsic phycobilisomes for cyanobacteria, and membrane-embedded chlorophyll a/b
      proteins in plants.

PMID- 15977057
TI  - Elucidation of the molecular structures of components of the phycobilisome:
      reconstructing a giant.
AB  - The molecular architectures of photosynthetic complexes are rapidly becoming
      available through the power of X-ray crystallography. These complexes are
      comprised of antenna complexes, which absorb and transfer energy into
      photochemical reaction centers. Most reaction centers, found in both oxygenic and
      non-oxygenic species, are connected to transmembrane chlorophyll containing
      antennas, and the crystal structures of these antennas contain information on the
      structure of the entire complex as well as clear indications on their modes of
      functional association. In cyanobacteria and red alga, most of the Photosystem II
      associated light harvesting is performed by an enormous (3-7 MDa) membrane
      attached complex called the phycobilisome (PBS). While the crystal structures of
      many isolated components of different PBSs have been determined, the structure of
      the entire complex as well as its manner of association with Photosystem II can
      only be suggested. In this review, the structural information obtained on the
      isolated components will be described. The structural information obtained from
      the components provides the basis for the modeled reconstruction of this giant
      complex.

PMID- 15977058
TI  - Structural and functional organization of the peripheral light-harvesting system
      in photosystem I.
AB  - This review centers on the structural and functional organization of the light
      harvesting system in the peripheral antenna of Photosystem I (LHC I) and its
      energy coupling to the Photosystem I (PS I) core antenna network in view of
      recently available structural models of the eukaryotic Photosystem I-LHC I
      complex, eukaryotic LHC II complexes and the cyanobacterial Photosystem I core. A
      structural model based on the 3D homology of Lhca4 with LHC II is used for
      analysis of the principles of pigment arrangement in the LHC I peripheral
      antenna, for prediction of the protein ligands for the pigments that are unique
      for LHC I and for estimates of the excitonic coupling in strongly interacting
      pigment dimers. The presence of chlorophyll clusters with strong pigment-pigment
      interactions is a structural feature of PS I, resulting in the characteristic red
      shifted fluorescence. Analysis of the interactions between the PS I core antenna
      and the peripheral antenna leads to the suggestion that the specific function of
      the red pigments is likely to be determined by their localization with respect to
      the reaction center. In the PS I core antenna, the Chl clusters with a different
      magnitude of low energy shift contribute to better spectral overlap of Chls in
      the reaction center and the Chls of the antenna network, concentrate the
      excitation around the reaction center and participate in downhill enhancement of
      energy transfer from LHC II to the PS I core. Chlorophyll clusters forming
      terminal emitters in LHC I are likely to be involved in photoprotection against
      excess energy.

PMID- 15977059
TI  - Structure of cyanobacterial photosystem I.
AB  - Photosystem I is one of the most fascinating membrane protein complexes for which
      a structure has been determined. It functions as a bio-solar energy converter,
      catalyzing one of the first steps of oxygenic photosynthesis. It captures the
      light of the sun by means of a large antenna system, consisting of chlorophylls
      and carotenoids, and transfers the energy to the center of the complex, driving
      the transmembrane electron transfer from plastoquinone to ferredoxin.
      Cyanobacterial Photosystem I is a trimer consisting of 36 proteins to which 381
      cofactors are non-covalently attached. This review discusses the complex function
      of Photosystem I based on the structure of the complex at 2.5 A resolution as
      well as spectroscopic and biochemical data.

PMID- 15977060
TI  - X-ray spectroscopy of the Mn4Ca cluster in the water-oxidation complex of
      Photosystem II.
AB  - The water-oxidation complex of Photosystem II (PS II) contains a heteronuclear
      cluster of 4 Mn atoms and a Ca atom. Ligands to the metal cluster involve
      bridging O atoms, and O and N atoms from amino acid side-chains of the D1
      polypeptide of PS II, with likely additional contributions from water and CP43.
      Although moderate resolution X-ray diffraction-based structures of PS II have
      been reported recently, and the location of the Mn4Ca cluster has been
      identified, the structures are not resolved at the atomic level. X-ray absorption
      (XAS), emission (XES), resonant inelastic X-ray scattering (RIXS) and extended X
      ray absorption fine structure (EXAFS) provide independent and potentially highly
      accurate sources of structural and oxidation-state information. When combined
      with polarized X-ray studies of oriented membranes or single-crystals of PS II, a
      more detailed picture of the cluster and its disposition in PS II is obtained.

PMID- 15977061
TI  - Structural and functional studies on the tetraheme cytochrome subunit and its
      electron donor proteins: the possible docking mechanisms during the electron
      transfer reaction.
AB  - The photosynthetic reaction centers (RCs) classified as the group II possess a
      peripheral cytochrome (Cyt) subunit, which serves as the electron mediator to the
      special-pair. In the cycle of the photosynthetic electron transfer reactions, the
      Cyt subunit accepts electrons from soluble electron carrier proteins, and re
      reduces the photo-oxidized special-pair of the bacteriochlorophyll.
      Physiologically, high-potential cytochromes such as the cytochrome c2 and the
      high-potential iron-sulfur protein (HiPIP) function as the electron donors to the
      Cyt subunit. Most of the Cyt subunits possess four heme c groups, and it was
      unclear which heme group first accepts the electron from the electron donor. The
      most distal heme to the special-pair, the heme-1, has a lower redox potential
      than the electron donors, which makes it difficult to understand the electron
      transfer mechanism mediated by the Cyt subunit. Extensive mutagenesis combined
      with kinetic studies has made a great contribution to our understanding of the
      molecular interaction mechanisms, and has demonstrated the importance of the
      region close to the heme-1 in the electron transfer. Moreover, crystallographic
      studies have elucidated two high-resolution three-dimensional structures for the
      RCs containing the Cyt subunit, the Blastochloris viridis and Thermochromatium
      tepidum RCs, as well as the structures of their electron donors. An examination
      of the structural data also suggested that the binding sites for both the
      cytochrome c2 and the HiPIP are located adjacent to the solvent-accessible edge
      of the heme-1. In addition, it is also indicated by the structural and
      biochemical data that the cytochrome c2 and the HiPIP dock with the Cyt subunit
      by c2 is recognized through electrostatic interactions while hydrophobic
      interactions are important in the HiPIP docking.

PMID- 15977062
TI  - The structure and function of the cytochrome c2: reaction center electron
      transfer complex from Rhodobacter sphaeroides.
AB  - In the photosynthetic bacterium, Rhodobacter sphaeroides, the mobile electron
      carrier, cytochrome c2 (cyt c2) transfers an electron from reduced heme to the
      photooxidized bacteriochlorophyll dimer in the membrane bound reaction center
      (RC) as part of the light induced cyclic electron transfer chain. A complex
      between these two proteins that is active in electron transfer has been
      crystallized and its structure determined by X-ray diffraction. The structure of
      the cyt:RC complex shows the cyt c2 (cyt c2) positioned at the center of the
      periplasmic surface of the RC. The exposed heme edge from cyt c2 is in close
      tunneling contact with the electron acceptor through an intervening bridging
      residue, Tyr L162 located on the RC surface directly above the
      bacteriochlorophyll dimer. The binding interface between the two proteins can be
      divided into two regions: a short-range interaction domain and a long-range
      interaction domain. The short-range domain includes residues immediately
      surrounding the tunneling contact region around the heme and Tyr L162 that
      display close intermolecular contacts optimized for electron transfer. These
      include a small number of hydrophobic interactions, hydrogen bonds and a pi
      cation interaction. The long-range interaction domain consists of solvated
      complementary charged residues; positively charged residues from the cyt and
      negatively charged residues from the RC that provide long range electrostatic
      interactions that can steer the two proteins into position for rapid association.

PMID- 15977063
TI  - High potential iron-sulfur proteins and their role as soluble electron carriers
      in bacterial photosynthesis: tale of a discovery.
AB  - This review is an attempt to retrace the chronicle of the discovery of the role
      of high-potential iron-sulfur proteins (HiPIPs) as electron carriers in the
      photosynthetic chain of bacteria. Data and facts are presented through the
      magnifying lenses of the authors, using their best judgment to filter and
      elaborate on the many facets of the research carried out on this class of
      proteins over the years. The tale is divided into four main periods: the seeds,
      the blooming, the ripening, and the harvest, representing the times from the
      discovery of these proteins to the most recent advancements in the understanding
      of the relationship between their structure and their function.

PMID- 15977064
TI  - Structure of the cytochrome b6f complex: new prosthetic groups, Q-space, and the
      'hors d'oeuvres hypothesis' for assembly of the complex.
AB  - 3-A crystal structures of the cytochrome b6f complex have provided a structural
      framework for the photosynthetic electron transport chain. The structures of the
      220,000 molecular weight dimeric cytochrome b6f complex from the thermophilic
      cyanobacterium, Mastigocladis laminosus (Kurisu et al. 2003, Science 302: 1009
      1014), and the green alga, Chlamydomonas reinhardtii (Stroebel et al. 2003,
      Nature 426: 413-418), are very similar. The latter is the first structure of a
      integral membrane photosynthetic electron transport complex from a eukaryotic
      source. The M. laminosus and C. reinhardtii structures have provided structural
      information and experimental insights to the properties and functions of three
      native and novel prosthetic groups, a chlorophyll a, a beta-carotene, and a
      unique heme x, one copy of which is found in each monomer of the cytochrome b6f
      complex, but not the cytochrome bc1 complex from the mitochondrial respiratory
      chain of animals and yeast. Several functional insights have emerged from the
      structures including the function of the dimer; the properties of heme x; the
      function of the inter-monomer quinone-exchange cavity; a quinone diffusion
      pathway through relatively narrow crevices or portals; a modified reaction scheme
      for n-side quinone redox reactions; a necessarily novel mechanism for quenching
      of the bound chlorophyll triplet state; a possible role for the bound chlorophyll
      a in activation of the LHC kinase; and a structural and assembly role for the
      four small PetG, L, M, and N subunits. An 'hors d'oeuvres hypothesis' for
      assembly of the complex is proposed for the small 'hydrophobic stick' or 'picket
      fence' polypeptides at the periphery of the complex, based on the cis-positive
      orientation of the small hydrophobic subunits and the 'toothpick' binding mode of
      the beta-carotene.

PMID- 15977065
TI  - Isolation of human periosteum-derived progenitor cells using immunophenotypes for
      chondrogenesis.
AB  - Periosteum-derived progenitor cells (PDPCs) were isolated by characteristic
      surface markers. Reproducibility of immunophenotypes of the PDPCs was
      characterized by flow cytometric analysis using fluorescence-activated cell
      sorter (FACS). SH2(+), SH3(+), SH4(+), CD9(+), CD90(+) and CD105(+) were
      important eternal characteristic cell surface markers for the PDPCs. The
      characterized PDPCs maintained their chondrogenic potential in pellet cultures
      until the 15th passage from primary cell culture.

PMID- 15977066
TI  - Phellinus linteus grown on germinated brown rice suppresses IgE production by the
      modulation of Th1/Th2 balance in murine mesenteric lymph node lymphocytes.
AB  - We compared the immunomodulating effects of Phellinus linteus (PL), germinated
      brown rice (BR) and P. linteus grown on germinated brown rice (PB) on IgE
      production in murine mesenteric lymph node (MLN) lymphocytes. All extracts
      decreased IgE concentrations by 43--65% compared to control mice in both serum
      and MLN lymphocytes. In addition, PL and PB increased the proportion of CD4(+) T
      cells by 9% and 12% in MLN lymphocytes. IFN-gamma concentration, Th1 cytokine,
      was significantly increased by 44--67%, whereas IL-4 and IL-10 concentrations,
      Th2 cytokine, significantly decreased by 30--60% in the three treated groups
      compared to control group. These results suggest that PB suppresses IgE
      production through the modulation of Th1/Th2 balance to down-regulate Th2
      response in MLN lymphocytes, even though a synergistic effect of PB was not
      found.

PMID- 15977067
TI  - Fast screening target sites for RNA interference using a cell-free system.
AB  - A fast and simple procedure to screen target sites for RNA interference by using
      RNA in a cell-free system of Hela cells, and then evaluating the efficiency by
      Northern blotting, is described. This procedure produces results with an
      identical reliability compared to those described previously but which are more
      time-consuming than this present method.

PMID- 15977068
TI  - GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with
      DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47).
AB  - GABA(A) receptor-associated protein (GABARAP) is a 14-kDa cytoplasmic protein
      initially identified as a molecular chaperone for GABA(A) receptor in cortical
      neurons. However, evidence indicates that the function of GABARAP is much broader
      than a specific role in neuronal cells. As an initial step to define the
      biological role of GABARAP, we searched for binding partners of GABARAP using co
      immunoprecipitation coupled with LC-MS/MS analysis. As a result, DEAD (Asp-Glu
      Ala-Asp/His) box polypeptide 47 (DDX 47), recently identified as RNA helicase, is
      identified as a binding partner of GABARAP. An interaction between GABARAP and
      DDX 47 was further confirmed by yeast two-hybrid systems. Further, co
      transfection of GABARAP and DDX47 cDNA into a tumor cell line induces apoptosis.
      This result may be the first evidence showing that GABARAP and DDX 47 are
      involved in the apoptotic process.

PMID- 15977069
TI  - Isolation of RNA of high quality and yield from Ginkgo biloba leaves.
AB  - An improved protocol was developed to isolate total RNA in good yield and
      integrity from Ginkgo biloba leaves containing high levels of flavonoid
      glycosides, terpene lactones, carbohydrates and polyphenolic secondary
      metabolites. Polyvinylpolypyrrolidone at 2% and beta-mercaptoethanol at 4% were
      added to the standard CTAB extraction buffer and, after chloroform and phenol
      extraction, the pellet obtained by ethanol/acetate precipitation was washed and a
      second phenol/chloroform extraction was introduced to remove co-precipitated
      polysaccharides. Both A(260)/A(230) and A(260)/A(280) absorbancy ratios of
      isolated RNA were around 2 and the yield was about 0.4 mg g(--1) fresh weight. At
      least seven distinct rRNA bands were detected by denaturing gel electrophoresis.
      Sharp hybridization signals were obtained from Northern blots with both nuclear
      and plastid gene probes. Two gene fragments: nuclear-encoded cab and chloroplast
      encoded rbcL were successfully amplified by RT-PCR, suggesting the integrity of
      isolated RNA. The total RNA isolated by this protocol is of sufficient quality
      for subsequent molecular applications.

PMID- 15977070
TI  - Enzymatic degradation of dibutyl phthalate and toxicity of its degradation
      products.
AB  - Dibutyl phthalate (DBP) was more efficiently degraded by cutinase compared to
      yeast esterase; i.e. almost 80% of initial DBP (500 mg l(-1)) was decomposed
      within 7.5 h, and nearly 50% of the degraded DBP disappeared within the initial
      30 min. The toxicity of the final DBP degradation products were investigated
      using various recombinant bioluminescent bacteria. Butyl methyl phthalate, the
      major product of degradation by the esterase, was an oxidative toxic hazard that
      damaged protein synthesis.

PMID- 15977071
TI  - Cloning and expression of the gene encoding Streptomyces coelicolor A3(2) alpha
      galactosidase belonging to family 36.
AB  - The alpha-galactosidase gene of Streptomyces coelicolor A3(2) was cloned,
      expressed in Escherichia coli and characterized. It consisted of 1497 nucleotides
      encoding a protein of 499 amino acids with a predicted molecular weight of
      57,385. The observed homology between the deduced amino acid sequences of the
      enzyme and alpha-galactosidase from Thermus thermophilus was over 40%. The alpha
      galactosidase gene was assigned to family 36 of the glycosyl hydrolases. The
      enzyme purified from recombinant E. coli showed optimal activity at 40 degrees C
      and pH 7. The enzyme hydrolyzed p-nitrophenyl-alpha-D -galactopyroside,
      raffinose, stachyose but not melibiose and galactomanno-oligosaccharides,
      indicating that this enzyme recognizes not only the galactose moiety but also
      other substrates.

PMID- 15977072
TI  - Chitinases from Serratia marcescens Nima.
AB  - Chitinolytic activity of Serratia marcescens Nima (130 U ml(-1)) was up to 43
      times higher than those produced by other S. marcescens strains. This strain
      synthesized an endochitinase (Chi-60), an exochitinase (Chi-50) and a novel N
      acetylglucosaminidase. This latter showed two putative isoforms (Chi-180.5 and
      Chi-180.8) with isoelectric points of 5 and 8.1, respectively.

PMID- 15977073
TI  - Protection of osteoblastic cells from freeze/thaw cycle-induced oxidative stress
      by green tea polyphenol.
AB  - Green tea polyphenol (GTP) together with dimethylsulphoxide (DMSO) were added to
      a freezing solution of osteoblastic cells (rat calvarial osteoblasts and human
      osteosarcoma cells) exposed to repeated freeze/thaw cycles (FTC) to induce
      oxidative stress. When cells were subjected to 3 FTCs, freezing medium containing
      10% (v/v) DMSO and 500 mug GTP ml(-1) significantly (p<0.05) suppressed cell
      detachment and growth inhibition by over 63% and protected cell morphology.
      Furthermore, the alkaline phosphatase activity of osteoblastic cells was
      appreciably maintained after 2 and 3 FTCs in this mixture. Polyphenols may thus
      be of use as a cell cryopreservant and be advantageous in such fields as cell
      transplantation and tissue engineering.

PMID- 15977074
TI  - Increased erythromycin production by alginate as a medium ingredient or
      immobilization support in cultures of Saccharopolyspora erythraea.
AB  - Erythromycin production by Saccharopolyspora erythraea immobilized in 2% (w/v)
      calcium alginate or grown in medium containing 20 g sodium alginate/l inoculated
      with free cells was almost twice more than that of the control. S. erythraea did
      not consume alginate, agar, dextran, silicon antifoaming agent or cyclodextrin as
      a carbon source, although, all of these increased the production of erythromycin.
      Highest titer of erythromycin (2.3 times more than that of the control) was
      achieved in medium containing 1 g agar/l.

PMID- 15977075
TI  - Recombinant extracellular matrix-like proteins with repetitive elastin or
      collagen-like functional motifs.
AB  - Using overlap elongation PCR, we created repetitive DNA libraries encoding the
      elastin VPGVG and collagen-like GERGDRGDP sequences. From these libraries we
      isolated two repetitive DNA sequences, Col-5 encoding [(GERGDRGDP)(5)GER], and
      Ela-16 encoding [(VPGVG)(16)VPG]. Both proteins were expressed as thioredoxin
      fusion proteins. The resulting recombinant extracellular matrix-like proteins had
      the expected properties (cell adhesive ability and thermally responsive
      structural change) of the functional motif sequence unit used.

PMID- 15977076
TI  - Conformational biosensor for diagnosis of prion diseases.
AB  - A fluorescence technology to monitor the proliferation of amyloidogenic
      neurological disorders is proposed. A crude brain homogenate (0.01%) from animals
      infected with a transmissible spongiform encephalopathy is employed as a
      catalytic medium initiating conformational changes in 520 nM polypeptide
      biosensors (Tris/trifluoroethanol 50% mixture at pH 7). The fluorescence methods
      utilize pyrene residues covalently attached to the peptide ends. The coil-to-beta
      strand transitions in biosensor molecules cause elevation of a distinct
      fluorescence band of the pyrene aggregates (i.e. excimers). This approach enables
      the detection of infectious prion proteins at fmol, does not require antibody
      binding or protease treatment. Technology might be adopted for diagnosing a large
      variety of conformational disorders as well as for generic high-throughput
      screening of the amyloidogenic potential in plasma.

PMID- 15977078
TI  - Bile duct injuries at laparoscopic cholecystectomy: a single-institution
      prospective study. Acute cholecystitis indicates an increased risk.
AB  - During the last decade laparoscopic cholecystectomy (LC) has become established
      as the gold standard. The drawbacks in the form of bile duct (BD) injuries have
      also come into focus. We present the results of a prospective, consecutive series
      of 1568 patients with reference to BD injuries regarding risks, management, and
      preventive measures. The significant complications of all patients operated upon
      with LC between October 1999 and December 2003 were recorded prospectively. BD
      injuries were classified according to Strasberg into types A-E. Transected major
      BDs, injuries of type E, were regarded as "major" injuries and types A, B, C, and
      D were "minor" injuries. Major BDs were transected in five patients (0.3%), three
      of whom had acute cholecystitis. In the two patients operated on electively, the
      BD injuries were detected postoperatively, while they were detected
      intraoperatively when the operation was performed of necessity. The BDs were all
      reconstructed with a Roux-en-Y hepaticojejunostomy. Two patients had anastomotic
      strictures. Minor BD injuries were encountered in 19 patients (1.2%). The 13
      patients with leakage from the cystic duct or gallbladder bed, injury type A,
      were treated by endoscopic (ERC) stenting without sequelae. Five patients
      sustained a lateral BD injury, type D; they were treated with a simple suture
      over a T-tube (at LC) or endoscopically (ERC) without further problems. A
      transected aberrant right hepatic BD, type C injury, was due to its small-caliber
      sutured. Minor BD injuries could be managed at the primary hospital if the
      endoscopic expertise were at hand. Acute cholecystitis seems to be a risk factor
      for BD injuries.

PMID- 15977079
TI  - Relationship between tissue ingrowth and mesh contraction.
AB  - Contraction is a well-documented phenomenon occurring within two months of mesh
      implantation. Its etiology is unknown, but it is suggested to occur as a result
      of inadequate tissue ingrowth into the mesh and has been associated with hernia
      recurrence. In continuation of our previous studies, we compared tissue ingrowth
      characteristics of large patches of polyester (PE) and heavyweight polypropylene
      (PP) and their effect on mesh contraction. The materials used were eight PE and
      eight PP meshes measuring 10 x 10 cm2. After random assignment to the
      implantation sites, the meshes were fixed to the abdominal wall fascia of swine
      using interrupted polypropylene sutures. A necropsy was performed three months
      after surgery for evaluation of mesh contraction/shrinkage. Using a tensiometer,
      tissue ingrowth was assessed by measuring the force necessary to detach the mesh
      from the fascia. Histologic analysis included inflammatory and fibroblastic
      reactions, scored on a 0-4 point scale. One swine developed a severe wound
      infection that involved two PP meshes and was therefore excluded from the study.
      The mean area covered by the PE meshes (87 +/- 7 cm2) was significantly larger
      than the area covered by the PP meshes (67 +/- 14 cm2) (p = 0.006). Tissue
      ingrowth force of the PE meshes (194 +/- 37 N) had a trend toward being higher
      than that of the PP meshes (159 +/- 43 N), although it did not reach statistical
      significance. There was no difference in histologic inflammatory and fibroblastic
      reactions between mesh types. There was a significant correlation between tissue
      ingrowth force and mesh size (p = 0.03, 95% CI: 0.05-0.84). Our results confirm
      those from previous studies in that mesh materials undergo significant
      contraction after suture fixation to the fascia. PE resulted in less contraction
      than polypropylene. A strong integration of the mesh into the tissue helps
      prevent this phenomenon, which is evidenced by a significant correlation between
      tissue ingrowth force and mesh size.

PMID- 15977083
TI  - Global perspectives--Zimbabwe.

PMID- 15977080
TI  - Long-term efficacy of distal splenorenal shunt with splenopancreatic and gastric
      disconnection for esophagogastric varices in patients with idiopathic portal
      hypertension.
AB  - Idiopathic portal hypertension (IPH) requires invasive measures to prevent
      rupture and bleeding of esophagogastric varices. However, the long-term results
      of shunt surgery for IPH have not been reported. In particular, the pros and cons
      of surgery that preserves the spleen and its long-term hematologic effects have
      not been described. The records of 15 patients who underwent distal splenorenal
      shunt with splenopancreatic and gastric disconnection (DSRS with SPGD) for IPH
      between 1983 and 1998 was reviewed retrospectively. One patient died within 3
      years of surgery, for a 3-year survival rate of 93%; the 10-year survival rate
      was 64%. Three patients (18%) suffered rebleeding from esophagogastric varices.
      The white blood cell and platelet counts were higher 3-5 years and 7-13 years
      postoperatively compared with preoperative values. Four of five patients who
      underwent postoperative computed tomography had a smaller spleen postoperatively.
      DSRS with SPGD provides long-term hemostasis for esophagogastric variceal
      bleeding in IPH and alleviates hypersplenism. DSRS with SPGD is an effective
      treatment for patients with IPH in whom long-term survival is expected.

PMID- 15977084
TI  - Migraine: traditional or "innovative" treatment? A preliminary case-control
      study.
AB  - The aim of this preliminary case-control study was to compare, in patients with
      migraine and PFO, transcatheter closure of PFO vs. medical treatments. Twelve
      patients were treated with antimigraine drugs and twelve underwent percutaneous
      transcatheter closure. All patients were followed-up for 12 months. Our
      preliminary results seem to confirm that, compared to medical treatment, PFO
      closure is by far more effective in reducing both frequency, duration and
      intensity of migraine attacks. Furthermore, the occurrence of prodromal aura is
      almost abolished.

PMID- 15977085
TI  - Evaluating the risk of potential acid sulfate soils and habitat modification for
      mosquito control (runneling) in coastal salt marshes: comparing methods and
      managing the risk.
AB  - Coastal environments in Australia are under development pressures. Human
      settlement encroaches on disease vector salt marsh mosquito breeding areas that
      are underlain by potential acid sulfate soils (PASS). Altering the hydrology by
      runneling solves the mosquito problem but may lead to acid sulfate problems.
      Appropriate analytical tools can assess the risk to the environment. The
      objective of the research was to compare three methods of assessing PASS. The
      study area was a low-lying intertidal subtropical salt marsh that was being
      considered for runneling. The results indicated that using field pH and field
      peroxide pH (and the relationship between these), and also the peroxide oxidation
      combined acidity and sulfate (POCAS) test, appeared to overestimate the potential
      acidity. This was because the source of acidity in the intertidal salt marsh
      includes a large organic content, which is not a major environmental concern. The
      chromium-reducible sulfur test, which is not affected by organic content, was
      found to provide the most appropriate assessment, and is recommended for use in
      highly organic salt marshes.

PMID- 15977086
TI  - Tree structure and diversity in human-impacted littoral forests, madagascar.
AB  - This research surveyed human-impacted littoral forests in southeastern Madagascar
      to determine (i) how forest structural features, indicative of human impact, are
      related to total, utilitarian, and endemic tree diversity; (ii) the distribution,
      abundance, and demographics of tree species groups (i.e., total, useful, endemic)
      across the landscape; and (iii) the amount of basal area available per human use
      category. We also use these data to consider issues of sustainable use and how
      human impact may influence littoral forest tree community composition across the
      landscape. Within 22 transects of 400 m2 each, we recorded a total of 135 tree
      species and 2155 individuals. Seventy-nine species (58%) were utilitarian and 56
      (42%) were nonutilitarian species. Of the 2155 individuals, 1827 (84%) trees were
      utilitarian species. We recorded 23 endemic species (17% of the total species)
      and 17 (74%) of these were utilitarian species. Basal area was significantly
      correlated with Shannon Weiner Index values for total (r = 0.64, P < 0.01),
      utilitarian (r = 0.58, P < 0.01), and endemic tree diversity (r = 0.85, P <
      0.01). Basal area was significantly correlated with the Simpson's index values
      for the endemic species (r = 0.74, P < 0.01). These correlations suggest that
      endemic tree species, of high global conservation value, may be the species group
      most influenced by changes in forest structure. Utilitarian species constituted
      84% of the total basal area. The use category contributing the highest amount of
      basal area to the landscape was firewood. The results presented herein
      demonstrate that the landscape of southeastern Madagascar, commonly perceived as
      degraded, retains high value for both global conservation purposes and for local
      livelihoods. Thus, valuable opportunities may exist for developing conservation
      incentives that leverage both global and local conservation needs.

PMID- 15977087
TI  - Thoracic outlet syndrome.
AB  - Diagnosis and treatment of thoracic outlet syndrome (TOS) involves neurologists,
      physiatrists, family physicians, orthopedic surgeons, vascular surgeons, thoracic
      surgeons, neurosurgeons and sometimes psychiatrists. It is generally accepted
      that TOS is caused by compression of brachial plexus elements or subclavian
      vessels in their passage from the cervical area toward the axilla and proximal
      arm either at the interscalene triangle, the costoclavicular triangle, or the
      subcoracoid space. Cervical ribs, anomalous muscles, and fibrous bands may
      further constrict these areas. Patients with thoracic outlet syndrome usually
      have aching type pain radiating from their scapula down the upper extremity. It
      is more common in women, and between 20 and 50 years of age. In order to diagnose
      accurately, clinical presentation may be evaluated as neurogenic TOS, those with
      compression of the brachial plexus, or vascular TOS, those with compression of
      the subclavian vessels and nonspecific-type TOS. The diagnosis of TOS can be made
      by history, physical examination, provocative tests, ultrasound, radiological
      evaluation and electrodiagnostic evaluation. For most patients with TOS,
      conservative treatment is offered. Definitive treatment involves surgical
      decompression of the related structures.

PMID- 15977088
TI  - [Chronic pain and rehabilitation].
AB  - The perception and interpretation of pain is the end point of an interaction of
      cognitive, cultural, and environmental factors and this complex interaction
      effects the pain response and quality of life of each person which shows that
      pain perception and the verbal and behavioral response shows variations and is
      specific for each patient. Chronic pain can be due to Fibromyalgia Syndrome (FMS)
      and Neuropathic Pain (NP) where the underlying pathophysiologic mechanisms are
      being revealed or it can be chronic low back pain (CLBP) where pain persists in
      spite of healing of tissue and no underlying pathologic mechanism can be
      defected. Central sensitization, inhibition of descending pain inhibitory
      systems, functional changes in autonomic nervous system amd neurotransmitter as
      well as changes in stress response system are factors contributing to the
      initiation and maintenance of pain and cognitive, behavioral factors are also
      important contributors in chronic pain. Biopsychosocial and biomedical mechanisms
      should be assessed in the rehabilitation interventions. The aims of
      rehabilitation in chronic pain are to increase activity tolerance, functional
      capacity and to decrease socio-economic loads. The targets of activity should be
      physical, functional and social. Psychologic based programs as cognitive
      behavioral techniques and operant conditioning are also valid procedures in
      rehabilitation of chronic pain patients. Rehabilitation should be
      multidisciplinary and of long-term targeted to valid out-come for success.

PMID- 15977089
TI  - [Percutaneous lumber nucleoplasty].
AB  - Low-back pain is one of the most common causes for seeking professional medical
      assistance and the most frequent cause of absence from work. It is not rare that
      the intervertebral discs are the etiological factor. Degenerated discs with
      internal disruptions may cause axial back pain whereas protrusion or herniation
      of a disc may result in radicular pain. Open surgical procedures targeting the
      intervertebral discs are carried out frequently for years. But especially because
      of its lack of superiority over the conventional therapies in the long-term and
      the risk of development of failed back surgery syndrome, the investigators are
      forced to develop minimally invasive techniques of disc decompression. In the
      last two decades, better understanding of the spinal anatomy, function and pain
      generating mechanisms along with the technological achievements, has accelerated
      the development of many modalities for the treatment of low back pain.
      Chemonucleolysis, automated percutaneous lumbar discectomy (APLD), intradiscal
      laser discectomy, intradiscal electrothermal therapy (IDET) and most recently
      percutaneous nucleoplasty are the minimally invasive techniques developed for
      this aim. Percutaneous nucleoplasty is a minimally invasive technique which uses
      radiofrequency energy to ablate the nucleus pulposus in a controlled manner for
      disc decompression. The current data about this new technique is insufficient
      yet, but the preliminary reports indicate that the technique is relatively safe
      and the outcomes are encouraging.

PMID- 15977090
TI  - [Elongated styloid process (Eagle's syndrome): literature review and a case
      report].
AB  - Eagle's syndrome occurs when an elongated styloid process or calcified stylohyoid
      ligament causes recurrent throat pain or foreign body sensation, dysphagia, or
      facial pain. Additional symptoms may include neck or throat pain with radiation
      to the ipsilateral ear. The symptoms related to this condition can be confused
      with those attributed to a wide variety of facial neuralgias. Diagnosis can
      usually be made on physical examination by digital palpation of the styloid
      process in the tonsillar fossa. The treatment of Eagle's syndrome is primarily
      surgical. The styloid process can be shortened through an intraoral or external
      approach. We report a 51-year-old woman with the symptomatology of Eagle's
      syndrome and literature review.

PMID- 15977091
TI  - [The headache triggered with ingestion of hot and soft fizzy drinks: similarity
      with ice cream headache].
AB  - Ice cream headache is more frequent in migraineurs. This is probably due to the
      specific interactions between neural and vascular systems in migraine patients.
      Two patients suffering from ice cream headache reported us that a similar
      headache occurred during migraine attacks with various stimuli such as ingesting
      hot and fizzy drinks. In addition to the pace of ingestion and temperature of the
      material, central sensitization may also have a role in the occurrence of this
      pain. We think that various factors play role in this neuro-vascular interaction.
      Accepting the ice cream headache as a prototype of this neuro-vascular
      interaction could provide path to new concepts.

PMID- 15977092
TI  - Preemptive oral rofecoxib plus postoperative intraarticular bupivacaine for pain
      relief after arthroscopic knee surgery.
AB  - This study was designed to test the hypothesis whether preemptive administration
      of rofecoxib, a novel selective COX-2 inhibitor, can prolong intraarticular
      bupivacaine analgesia after arthroscopic knee surgery. Sixty-two patients were
      randomly assigned to one of the three groups. Group 1 (n=21) was administered
      oral rofecoxib 50 mg 1 h before surgery plus intraarticular 0.5 % bupivacaine 20
      ml postoperatively. Group 2 (n=21) was administered the same dose of bupivacaine.
      Group 3 (n=20) was administered saline 20 ml intraarticularly after surgery. Pain
      scores (VAS) were assessed at 30 min, 1, 2, 4, 6, 12 and 24 h postoperatively.
      Analgesia duration, analgesic (tramadol and tenoxicam) requirements, and adverse
      effects were recorded postoperatively for 24 h. Pain scores were significantly
      lower in the Group 1 at all time points (p<0.05, p<0.001) and were significantly
      lower in the Group 2 at 30 min (p<0.001), 1 and 4 h (p<0.05) compared to the
      Group 3. Pain scores were significantly lower in the Group 1 compared to the
      Group 2 during the first 4 h after surgery (p<0.05, p<0.001). Analgesia duration
      was longer in Group 1 than Group 2 or 3 (743.0 +/- 480.5 min versus 262.4 +/-
      292.2 min and 17.0 +/- 12.1 min; p<0.05, p<0.001 respectively), and in Group 2
      than Group 3 (p<0.05). Tramadol requirements were significantly less in Group 1
      than Group 2 and 3 (4.8 +/- 15.0 mg versus 40.5 +/- 43.6 mg and 67.5 +/- 24.5 mg;
      p<0.05, p<0.001 respectively), and in Group 2 than Group 3 (p<0.05). There were
      no significant differences among the groups regarding the tenoxicam requirements
      and adverse effects. In conclusion, the combination of oral rofecoxib
      administered preemptively and intraarticular bupivacaine administered
      postoperatively provided a significant analgesic benefit and decreased the opioid
      requirements after arthroscopic knee surgery, when compared to bupivacaine alone
      or saline.

PMID- 15977093
TI  - [The comparison of the effects and side effects of local anesthetic and opioid
      combinations in epidural patient controlled analgesia].
AB  - The aim of this study was to retrospectively evaluate the efficacy and side
      effects of local anesthetic and opioid combinations in 457 patients who have
      received epidural patient-controlled analgesia (EPCA). Hemodynamic parameters,
      numeric rating scale, sedation scores, the degree of motor and sensory blockage,
      the presence of side effects, the parameters of PCA device were recorded from the
      postoperative pain records. 253 patients received 0.1 % bupivacaine + 3 microg/ml
      fentanyl (Group B1F3), 80 patients received 0.125 % bupivacaine + 3 microg/ml
      fentanyl (Group B12F3), 43 patients received 0.125 % bupivacaine + 4 microg/ml
      fentanyl (Group B12F4), 46 patients received 0.1 % bupivacaine + 0.1 mg/ml
      morphine (Group B1M1) and 35 patients received 0.125 % bupivacaine + 0.1 mg/ml
      morphine (Group B12M1). Nausea was significantly higher in group B1M1 compared to
      B12F3, in group B12M1 compared to B1F3 and B12F3 (p<0.05), vomiting was
      significantly higher in group B1M1 and B12M1 (p<0.05) compared to B12F3, pruritus
      was significantly higher in group B12F4 compared to B12F3 and B1F3, in group B1M1
      compared to B1F3 and B12F3 and in group B12M1 compared to B1F3 and B12F3
      (p<0.05). As a result, in EPCA, the combination of bupivacaine and fentanyl
      provides as effective analgesia as the combination of bupivacaine and morphine
      and 3 mg/ml fentanyl admixture may be preferred with less side effects such as
      nausea, vomiting and pruritus.

PMID- 15977094
TI  - [Comparison of bupivacaine-fentanyl versus bupivacaine-morphine for patient
      controlled epidural analgesia].
AB  - Analgesic efficacy and possible side effects of bupivacaine-fentanyl (BF) and
      bupivacaine-morphine (BM) combinations for patient controlled epidural analgesia
      (PCEA) have been compared. Sixty ASA I-II patients who had PCEA following lower
      abdominal surgery were admitted to the study. Epidural catheter was inserted at
      the level of L3-4 or L4-5 following induction of general anesthesia. In Group BF
      epidural drug solution was prepared as bupivacaine 0.1 % and fentanyl 2
      microg/ml. In Group BM, solution was prepared as bupivacaine 0.1 % and morphine
      0.2 microg/ml. In both groups PCEA was set as; bolus dose: 4 ml, lock - out
      period: 20 minutes, 4 hour limit: 30 ml. VAS was measured at postoperative 1, 2,
      3, 6, 9, 12 and 24th hours. In both groups adequate postoperative analgesia was
      provided. VAS score was higher in Group BF than Group BM at postoperative 12th
      hour (p<0.05). One patient in Group BF had unilateral motor block, one patient in
      Group BM had respiratory depression responding to i.v. naloxon administration.
      The incidence of pruritus was higher in Group BM than Group BF (p<0.05). Both
      treatment modalities provided adequate postoperative analgesia, but the risk of
      respiratory depression with opioid use should be considered.

PMID- 15977095
TI  - [Reality about pain control: the knowledge and beliefs of nurses on the nature,
      assessment and management of pain].
AB  - The present research was conducted descriptively to define the approaches of
      nurses to the nature of pain, its assessment, and management. The research was
      carried out in October 2001 in Antalya with a scope of 227 nurses attending to
      the Second National Clinician Nurses' Congress. Initial aim was to include all
      286 nurses attending the congress, however, because 59 nurses refused to
      participate, the number of the participants finalized as 227. A data gathering
      form of 20 questions was used. Results were presented in percentages. At the end
      of the research, though the knowledge the nurses had on the nature of pain was
      satisfactory, their attitudes related with pain assessment and management were
      noted to be below expectations. These results point out a void in the nurses'
      knowledge pertaining to pain management. As a result, we consider imperative that
      the nurses should acknowledge the significance of pain and should improve their
      professional attitudes and knowledge in order to gain control over pain through a
      multidisciplinary approach and to prove the crucial and inevitable role of nurses
      in such a team.

PMID- 15977096
TI  - [Comparison of ropivacaine, ropivacaine plus tramadol and ropivacaine plus
      morphine in patients undergoing minor hand surgery].
AB  - In our study we aimed to compare the effects of ropivacaine alone, ropivacaine
      plus tramadol HCl, and ropivacaine plus morphine HCl used as intravenous regional
      anesthesia (IVRA), on duration to the initiation of analgesia, total analgesia
      time, analgesic requirement, sedation levels and hemodynamic parameters. 53
      patients undergoing minor hand surgery were included into the study. Patients
      were randomly divided into three groups to receive 40 ml of ropivacaine 0.2 %
      (Group R, n=18), ropivacaine 0.2 % plus 1 mg/kg tramadol HCl (Group RT, n=18),
      and ropivacaine 0.2 % plus 0.1 mg/kg morphine HCl (Group RM, n=17) as IVRA.
      Following the injection, the durations for the initiation of analgesia were
      recorded. Levels of sedation, analgesia (VAS) and hemodynamic parameters were
      recorded in 5 minute intervals throughout first 35 minutes intraoperatively and
      at 1, 5, 10, 15, 20, 30, 45 and 60th minutes postoperatively. Patients were asked
      about the initiation of pain and requirements of analgesic at the first
      postoperative day. The duration to the initiation of analgesia was similar
      between the groups. Total analgesia time was found to be 304.0 +/- 317.6 min in
      Group R, 327.0 +/- 316.5 min in Group RT, and 635.9 +/- 492.3 min in Group RM.
      The difference between Group R and RM was statistically significant (p<0.05).
      Analgesic requirements were similar between the groups (p>0.05). Mild local
      anesthetic toxicity was observed in Group RM in two patients. We conclude that,
      when used as IVRA, ropivacaine alone or with tramadol or morphine produced
      similar analgesia and surgery conditions, and ropivacaine plus morphine had more
      adverse effects besides its longer duration of analgesia.

PMID- 15977097
TI  - IFN-gamma low production capacity in type 1 diabetes mellitus patients at onset
      of disease.
AB  - In type 1 diabetes mellitus (T1DM), cytokines can be directly cytotoxic to beta
      cells, and/or play an indirect role influencing some cells of the immune system.
      Since several factors could impair cytokine serum levels, the purpose of our
      study was to longitudinally evaluate intracellular cytokines, in T1DM patients,
      and in subject at risk, by flow cytometry analysis. At T1DM onset we observed
      significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFN
      gamma in patients compared to controls and subjects at risk. The 15-month follow
      up patients showed significantly lower percentage of CD4 + and CD8 + cells
      producing IFN-gamma compared to the other groups. At 8-year follow-up no
      significant differences were observed among the groups in the percentage of cells
      producing cytokines. We could have considered "exhausted cells" or these T cell
      subsets may be migrated from peripheral blood to pancreas. On the other hand, our
      results are in agreement with those reported in literature: in animal model the
      absence of IFN-gamma production makes beta-cells highly susceptible to viral
      infection and subsequent attack by natural killer cells, which lead to
      hyperglycaemia and diabetes mellitus.

PMID- 15977098
TI  - A heteroplasmic mitochondrial DNA 3310 mutation in the ND1 gene in a patient with
      type 2 diabetes, hypertrophic cardiomyopathy, and mental retardation.
AB  - A mentally retarded 57-year-old Japanese man with maternally-inherited type 2
      diabetes was found to have hypertrophic cardiomyopathy (HCM) that was associated
      with pathological changes in the myocardial mitochondria. The mitochondrial DNA
      (mtDNA) of this patient was examined and a C3310 T mutation was found in the ND1
      gene, which resulted in the substitution of serine for proline. The normal 3310
      mtDNA band could not be detected by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) in mtDNA from his myocardium, pancreas,
      cerebral tissue, skeletal muscle, and lymphocytes. However two clones sequenced
      from his pancreatic tissue did not show this C3310 T mutation while forty-eight
      did. Mitochondria isolated from the lymphocytes of his two sisters also had this
      mutation. mtDNA point mutations in the ND1 gene region reported thus far have
      been mostly homoplasmic. However, the C3310 T point mutation that was found in
      this patient was heteroplasmic, which is a high level of mutation and may
      represent the pathogenic gene that was responsible for causing mitochondrial
      disease.

PMID- 15977099
TI  - Intense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not
      improve nitric oxide dependent endothelial function in type-2-diabetes--a
      multicenter, randomised, double-blind, three-arm placebo-controlled clinical
      trial.
AB  - Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction
      play a central role in the pathogenesis of atherosclerosis in
      hypercholesterolemia and in individuals with type 2 diabetes. It is unclear
      whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve
      endothelial function in subjects with type 2 diabetes as it is demonstrated in
      non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2
      mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised,
      double-blind, and three-arm placebo-controlled clinical trial. Endothelial
      function was assessed by nitric oxide-dependent flow mediated vasodilatation
      (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were
      enrolled in the study. Bayer Company undertook a voluntary action to withdraw
      cerivastatin from market, therefore the study was terminated earlier. At this
      point 77 patients were randomised, of which 58 completed the study (mean age 60
      +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all
      three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the
      0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group).
      Despite a significant reduction in cholesterol and LDL-cholesterol-levels after
      12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2
      mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was
      no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo,
      respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the
      study. Furthermore no difference in safety profile between cerivastatin and
      placebo was found. Despite a significant improvement in lipid profile under
      statin therapy, no improvement of endothelial dysfunction in terms of nitric
      oxide bioavailability could be detected.

PMID- 15977100
TI  - Ovarian function after radioiodine therapy in patients with thyroid cancer.
AB  - OBJECTIVE: To assess ovarian function in young women treated with radioiodine.
      METHODS: The study was conducted on 50 women with thyroid carcinoma aged less
      than 40 years (mean, 29.8 years), with regular menstrual cycles and normal FSH
      levels prior to radioiodine therapy. FSH determination was repeated 6 and 12
      months after radioiodine therapy (mean, 4.24 GBq iodine-131) and menstrual cycles
      were monitored during this period. RESULTS: Twenty percent of the patients
      reported amenorrhea during the first year. FSH levels increased after 6 months
      (from 5.1 +/- 1.8 to 10.6 +/- 2.2 IU/l, p < 0.00 001) and 28 % of the patients
      showed elevated values, which had returned to normal by the end of the first
      year. CONCLUSION: Radioiodine causes transitory alterations in ovarian function
      even in younger women and after a mean activity of 4.2 GBq (115 mCi).

PMID- 15977101
TI  - Increased visceral fat and impaired glucose tolerance predict the increased risk
      of metabolic syndrome in Japanese middle-aged men.
AB  - BACKGROUND: Impaired glucose tolerance (IGT) represents a stage of pre-diabetes
      and is a risk factor for future cardiovascular disease (CVD) which is a major
      cause of death in type 2 diabetes. The metabolic risk factors such as elevated
      blood pressure (elevated BP), abdominal obesity, dyslipidemia (elevated levels of
      total triglycerides [TG] and low levels of HDL cholesterol), and hyperglycemia
      precede the onset of the metabolic syndrome that increases the risk for CVD. This
      clustering is commonly associated with pre-diabetic hyperinsulinemia and it
      reflects peripheral insulin resistance. The present study documented that a
      visceral fat area (VFA) >/= 100 cm (2) can replace waist-to-hip ratios (WHR)
      associated with IGT or IFG/IGT as a critical risk for the development of the
      metabolic syndrome in Japanese middle-aged men. MATERIALS AND METHODS: A total of
      575 middle-aged Japanese men with fasting plasma glucose levels of 6.1 - 6.9
      mmol/l (impaired fasting glucose; IFG) were enrolled in the study. After a 75-g
      oral glucose tolerance test (OGTT), blood samples were collected 0 - 2 h later
      for determination of plasma glucose, insulin concentrations and other variables.
      Based on the results of an OGTT, the subjects were subgrouped into categories of
      glucose tolerance for further study. RESULTS: Subjects with IGT or IFG/IGT had
      significantly higher levels of metabolic abnormalities such as high BMI,
      increased AUC glucose, elevated HbA1c, high VFA, elevated BP, and increased TG
      levels when compared to NGT (normal glucose tolerance) (p < 0.001). Compensatory
      hyper-secretion of insulin was seen in all pre-diabetic subjects, and was higher
      in IFG/IGT subjects (681 +/- 33 pmol . h/l) than NGT (480 +/- 22 pmol . h/l) (p <
      0.01). The metabolic clustering including abnormal VFA, TG, HDL-C, and BP was
      strongly associated with the development of metabolic syndrome. Interestingly,
      VFA >/= 100 cm (2) adjusted for the Japanese correlates strongly with the
      development of the metabolic syndrome in preclinical IGT or IFG/IGT subjects,
      with odds ratios of 2.7 and higher. CONCLUSION: VFA >/= 100 cm (2) strongly
      correlates with prediabetic IGT or IFG/IGT which is possibly associated with
      underlying insulin resistance, and is a critical risk factor linked to the
      development of metabolic syndrome in Japanese middle-aged subjects with IGT or
      IFG/IGT.

PMID- 15977102
TI  - Lipoatrophy induced by subcutaneous administration of octreotide in the treatment
      of acromegaly.
AB  - Octreotide is the first somatostatin analogue to become available for clinical
      use in the treatment of acromegaly. To our knowledge, there are no reports
      describing lipoatrophy in patients treated with octreotide. Here, we report three
      patients who developed lipoatrophy after treatment with subcutaneous octreotide.
      Three patients (all women; 36, 43, and 50 years of age) with diagnosis of
      acromegaly due to pituitary macroadenoma who had undergone transsphenoidal
      surgery and radiotherapy received subcutaneos octreotide because of uncontrolled
      disease. The dose of octreotide was increased gradually in all patients.
      Lipoatrophy was noticed around the injection sites after about 6 years, 30
      months, and 4 years of subcutaneous octreotide treatment in all patients.
      Thereafter, subcutaneous octreotide treatment was changed to intramuscular
      octreotide-LAR injection in all patients. In two of them, lipoatrophy around all
      injection sites did not regress after about 8 and 12 months of octreotide-LAR
      treatment, respectively. In the third patient, lipoatrophy around the injection
      sites regressed after 12 months of octreotide-LAR treatment. These cases
      highlight a potential for subcutaneous octreotide to induce lipoatrophy. The
      underlying mechanism is unknown but an immunological mechanism which is seen in
      lipoatrophy induced by insulin may be involved in the pathogenesis. Besides;
      simple trauma, personal susceptibility, mistakes in the administration of the
      drug, a problem in drug pH, or an idiosyncratic reaction of adipocytes to
      octreotide or additives in the drug may have caused lipoatrophy in our patients.
      Lipoatrophy in these cases was observed on long-term subcutaneous octreotide
      administration. Although intramuscular octreotide-LAR has largely replaced
      subcutaneous octreotide, we suggest close clinical follow-up for lipoatrophy in
      patients who are still on subcutaneous octreotide.

PMID- 15977103
TI  - Analysis of secretory, immunostaining and clinical characteristics of human
      "functionless" pituitary adenomas: transdifferentiation or gonadotropinomas?
AB  - In this study, the central technique of in vitro culture has been used to further
      investigate whether LH/FSH-expressing, but clinically "functionless" pituitary
      adenomas are gonadotropinomas or whether their hormone secretion is due to
      transdifferentiation events. 664 "functionless" pituitary adenomas were examined
      for hormone secretion by in vitro culture and for hormone content by
      immunostaining. The results were correlated with the clinical findings. 40 % of
      the tumours (n = 263) secreted at least one of the gonadotropins alone, 8 % (n =
      53) exhibited various patterns of anterior pituitary hormones, whilst the
      remaining 52 % of tumours were not associated with any hormone. In the secretory
      tumours, immunostaining revealed only a few scattered hormone-containing cells (5
      to 15 %). Mild hyperprolactinaemia was observed in some cases, presumably because
      of pressure effects of the tumours. The majority of the patients suffered clear
      cut hypopituitarism (p < 0.05). Pre-operatively, gonadotropin hypersecretion was
      observed in 3 cases, but only one of these secreted hormones in culture.
      Interestingly, a higher proportion of tumours removed from patients with
      hypopituitarism showed secretory activity in vitro than those tumours removed
      from patients showing no hormonal dysfunction or hyperprolactinaemia. We conclude
      that the term "gonadotropinoma" to describe functionless pituitary tumours
      associated with LH and/or FSH secretion is a misnomer, because the presence of LH
      and/or FSH confirmed by in vitro methods in the present series is a result of
      only a few scattered cells. We suggest that primary pituitary tumour cells
      differentiate into a secretory type (transdifferentiation), possibly in response
      to altered serum hormone levels such as decreased steroids. Further work is
      required to identify the factors which trigger the altered cells'
      characteristics.

PMID- 15977104
TI  - Nesidioblastosis--a rare cause of hypoglycaemia in adults.
AB  - A case of suspected clinically hormonally active insulinoma in a 48-year-old
      woman is presented. Despite the lack of features, which might correspond to the
      insulinoma in radiological examinations, the patient was qualified for a distal
      subtotal pancreatectomy and then, due to persistent hyperinsulinism, for total
      pancreatectomy. The insulinoma was found neither in a palpable examination of the
      pancreas nor in the intraoperative ultrasonic examination. In a histopathological
      examination supplemented with immunohistochemical tests, nesidioblastosis - a
      rare cause of hypoglycaemia in adults - was diagnosed.

PMID- 15977106
TI  - [The specific problematic nature of prosthesis patient assessment].

PMID- 15977107
TI  - [Scientific award of the Federation of Pediatric Orthopedics 2006].

PMID- 15977108
TI  - [A national endoprosthesis registry for hand surgery].

PMID- 15977109
TI  - [Integrated health care--current status].

PMID- 15977110
TI  - [The "trouser test" as coordination test after total hip prostheses
      implantation].

PMID- 15977111
TI  - [Effective thrombosis prophylaxis with melagatran].

PMID- 15977112
TI  - [Optimized pain therapy: opioids estabish better with higher potency and lower
      dosage].

PMID- 15977113
TI  - [Osteoporosis--treatment with Calcium/Vitamin D].

PMID- 15977114
TI  - [Innovative knee prosthesis: with the quad sparing technique using a stretching
      apparatus].

PMID- 15977115
TI  - [Artificial discs: review, current status, outlook].
AB  - AIM: This paper gives an overview of the current status of artificial discs for
      the lumbar spine. METHODS: Recent publications and overviews in the literature
      with pro and contra opinions and the latest procedure of FDA approval are
      presented and discussed. Despite arguments to the contrary, an FDA panel is in
      favour of the premarket approval application for the Charite artificial disc
      because of good late follow-up results. Other lumbar artificial discs will
      follow. RESULTS: Follow-up studies only exist for the Charite and Prodisc
      endoprotheses. The results are comparable to those of lumbar fusion. However,
      randomized controlled studies are still missing. CONCLUSION: Proponents for
      lumbar artificial discs stand against the criticism of an unpredictable treatment
      for a condition that cannot be diagnosed with any precision. The current model
      should be a controlled indication with second opinions followed by professional
      surgery in spine centers.

PMID- 15977116
TI  - [The delayed OP--indications for surgery of lumbar disc herniations].
AB  - In Germany, lumbar disc herniations require surgical treatment in about 50,000
      patients/year. The clinical and socio-economical results are determined by the
      preoperative duration of symptoms and preoperative time out of work (highly
      predictive). Other parameters such as severity of neurological deficits,
      morphology of disc herniation, age, associated diseases, type of surgery, working
      conditions or litigation processes are only weak predictors of outcome.
      Postoperative improvement of clinical symptoms as well as professional
      reintegration is strongly determined by the time period between onset of symptoms
      and surgery. Surgery performed "too early" diminishes the chance for improvement
      by conservative therapy. If surgery is performed "too late" the risk of a bad
      result is high, and the reintegration of the patient into his preoperative social
      and professional activities may be prevented. The duration of conservative
      therapy including so-called semi-invasive procedures is critical in this sense.
      If a therapeutic success (= professional and social reintegration) cannot be
      achieved by conservative measures and if there is a clear morphological correlate
      (= disc herniations with corresponding clinical symptoms) of the clinical
      symptoms an early change of the strategy towards surgical therapy is recommended.

PMID- 15977117
TI  - [What do we know about the symptoms of back pain? Epidemiological results on
      prevalence, incidence, progression and risk factors].
AB  - AIMS: This paper provides an overview of epidemiological findings concerning the
      prevalence and incidence of back pain, the underlying risk factors and health
      care utilization due to back pain. METHODS: Besides epidemiological studies, data
      from health care statistics and cost-of-illness studies were included in the
      systematic search. Relevant publications were identified using electronic
      literature databases (in particular Medline). RESULTS: Back-related disorders,
      classified according to the ICD-10 M40-M54 key are the major cause for receiving
      disability benefits. While back pain leads to a frequent demand for medical
      services, loss of production because of temporal sick leave is the major economic
      factor. In total, the estimated annual costs caused by back pain range between 16
      and 22 billion euros. The life-time prevalence corresponds to the immense costs:
      80 % report having ever experienced back pain. The point prevalence lies between
      30 and 40 %. Approximately one-fourth to one-third of those affected suffer from
      clinically significant back pain. Recurrent as well as incident back pain is best
      predicted by prior back pain. The wide spectrum of other risk factors
      (depression, psychosocial distress, somatization, catastrophizing,
      dissatisfaction at work and sociodemographic as well as socioeconomic variables)
      underscores the multifaceted etiology of this symptom. CONCLUSION: Back pain
      belongs to the major individual and societal health problems in Germany. While
      extensive epidemiological evidence exists for the prevalence of back pain, its
      severity, course and associated risk factors, little systematic knowledge is
      available about the medical treatment of back pain.

PMID- 15977118
TI  - [What questions are appropriate for predicting the risk of chronic disease in
      patients suffering from acute low back pain?].
AB  - AIM: The objective of the study was to develop a brief questionnaire to determine
      the risk of chronification for patients suffering from lumbar (low) back pain who
      are consulting a physician for the first or second time. METHOD: At the outset,
      and again after six months, a questionnaire with 167 valid items for
      chronification was distributed to patients in orthopedic offices. After six
      months, patients were contacted by mail to inquire whether they were still
      suffering from back pain. Based on outcome (persistence of back pain/absence of
      back pain) and by means of logistic regression analysis, those variables were
      determined that could predict actual chronification. RESULTS: The following items
      were predictive: "How strong was your back pain during the last week when it was
      most tolerable?" and "How much residual pain would you be willing to tolerate
      while still considering the therapy successful?" (Acceptance value, beta = 0.61),
      patient's educational level (beta = - 0.44), massage is experienced as bringing
      relief (beta = 0.44), 5 items of the Zung scale for depression (beta = 0.42),
      items of the scale for catastrophizing thoughts (beta = 0.41) and items of the
      scale for feelings of helplessness (beta = - 0.39) of the Kiel pain inventory;
      duration of the back pain for longer than 1 week (beta = 0.38), pain in other
      parts of the body (beta = 0.37); and female gender (beta = 0.25) CONCLUSION:
      Based on these questions, it was possible to predict the chronification of back
      pain with a probability of 78.05 %. A corresponding questionnaire and an
      evaluative table were developed.

PMID- 15977119
TI  - [The FADI score--a possibility for the quantified differential diagnosis of
      discogenic pain].
AB  - AIM: Chronic, non-radicular low-back pain has varying reasons. The main causes
      are a zygoapophysial joint syndrome, discogenic pain, especially the rupture of
      the inner disc, the IS joint syndrome as well as a myofascial syndrome.
      Especially the differentiation between zygoapophysial joint pain and discogenic
      pain often proves to be difficult in the clinical routine. In the literature,
      different criteria can be found concerning the distinction of zygoapophysial
      joint pain and discogenic pain. Clinical criteria, criteria of imaging as well as
      intensive diagnostics are described. So far there is a lack of a summarizing
      evaluation of these aspects. METHOD: The FADI score uses clinical criteria with
      combinations of motion, consisting of rotation, side inclination, anteflexion and
      pressure-sensitive spots, imaging aspects and the invasive diagnostics by means
      of selective blockades of zygoapophysial joints and discography or rather disc
      stimulation. The examination results are summed up and judged as to their
      relevance as well as validity through our score. RESULTS: First of all the
      relevance of the single aspects was judged in a primary test with 30 patients.
      The diagnostic block and the clinical criteria for the zygoapophysial joint
      syndrome as well as discography and MRI for discogenic pain had the best results.
      Afterwards the score was tested in the clinical area with 56 patients and showed
      its value under clinical conditions. CONCLUSION: Especially when dealing with
      patients suffering from chronic back pain, the score serves to simplify the
      choice of a further therapy, including invasive procedures, or rather to avoid
      unnecessary major surgery at the spine.

PMID- 15977120
TI  - [How can I assess the back pain status in my patients? The Mainz chronic disease
      staging method and its prognostic value].
AB  - Chronification of pain is not just a simple matter of duration, although many
      publications still pretend that this is so. Chronification is more a spread of
      pain on the physical level, on duration and even more on the psychological and
      social levels. We present different models to explain this process. Instruments
      to evaluate the amount of chronification are presented in comparison, on the one
      hand the graduation of chronic pain by von Korff, on the other hand the Mainz
      pain staging system (MPSS). Results of different inquiries have shown the
      correlation between chronicity of pain and measurements of quality of life and
      effectiveness of medical treatment. Also the MPSS has a prognostic value about
      the effect of further treatment. To get a differentiated view on the results of
      examinations and treatment outcome, an evaluation of the chronification process
      of the patient's pain is a necessity.

PMID- 15977121
TI  - [epiDRB--a new minimally invasive concept for referencing in the field of
      computer-assisted orthopaedic surgery].
AB  - AIM: Optoelectronic navigation for computer-assisted orthopaedic surgery (CAOS)
      is based on a firm connection of bone with passive reflectors or active light
      emitting diodes in a specific three-dimensional pattern. Even a so-called
      "minimally-invasive" dynamic reference base (DRB) requires fixation with screws
      or clamps via incision of the skin. Consequently an originally percutaneous
      intervention would unnecessarily be extended to an open procedure. Thus, computer
      assisted navigation is rarely applied. Due to their tree-like design most DRB's
      interfere with the surgeon's actions and therefore are at permanent risk to be
      accidentally dislocated. Accordingly, the optic communication between the camera
      and the operative site may repeatedly be interrupted. The aim of the research was
      the development of a less bulky, more comfortable, stable and safely trackable
      device that can be fixed truly percutaneously. METHOD: With engineering support
      of the industrial partner the radiolucent epiDRB was developed. It can be fixed
      with two or more pins and gains additional stability from its epicutaneous
      position. The intraoperative applicability and reliability was experimentally
      tested. RESULTS: Its low centre of gravity and its flat design allow the device
      to be located directly in the area of interest. Thanks to its epicutaneous
      position and its particular shape the epiDRB may perpetually be tracked by the
      navigation system without hindering the surgeon's actions. Hence, the risk of
      being displaced by accident is minimised and the line of sight remains
      unaffected. CONCLUSION: With the newly developed epiDRB computer-assisted
      navigation becomes easier and safer to handle even in punctures and other
      percutaneous procedures at the spine as much as at the extremities without an
      unproportionate amount of additional trauma. Due to the special design
      referencing of more than one vertebral body is possible at one time, thus
      decreasing radiation exposure and increasing efficiency.

PMID- 15977122
TI  - [CT-based and CT-free navigation in total knee arthroplasty--a prospective
      comparative study with respects to clinical and radiological results].
AB  - AIM: Optimal component position in all planes and well-balanced soft tissues are
      factors for clinical outcome and survival time after total knee arthroplasty
      (TKA). With regard to clinical and radiological parameters, a comparative study
      between CT-based and CT-free navigation techniques was performed. METHOD: In this
      prospective study 44 patients (44 surgeries) were enrolled. One half of the
      surgeries were performed using a CT-based navigation system (group A), the other
      half using a CT-free system (group B). Pre-operatively and three months post
      operatively the patients were physically examined (Insall score, step test,
      anterior knee pain, subjective feeling of instability and patient satisfaction)
      and limb alignment was measured by radiographs (mechanical axis, tibial slope,
      lateral distal femur angle [LDFA], medial proximal tibia angle [MPTA]). The
      tolerable inaccuracy range for all radiological measurements was +/- 3 degrees.
      RESULTS: The radiological measurements showed a high accuracy but no significant
      differences (patients within tolerable range group A/B: mechanical axis 85.7/81.0
      %, tibial slope 95.2/90.5 %, LDFA 100/95.2 %, MPTA 90.5/95.2 %). For physical
      parameters we found a better ligament balancing in group B. CONCLUSION: The CT
      based module has an optimal planning procedure but costs more. The CT-free system
      provides equal radiological results and the availability of a useful ligament
      balancing module.

PMID- 15977123
TI  - [Technique evaluation for orthopedic use of Robodoc].
AB  - AIM: The aim of this study was to assess the clinical benefit and rate of
      complications of robot-assisted primary total hip replacement. METHODS:
      Electronic bibliographic databases, the reference lists of relevant articles and
      various health services research-related resources were analysed and selected
      studies were assessed using defined quality criteria. RESULTS: 57 publications
      and three HTA-reports were assessed. Only two prospective randomised controlled
      studies could be identified. There was no proof of clinical benefit but rather an
      increased incidence of complications. CONCLUSION: Patients must be informed on
      the risks, complications, benefits and especially alternatives to a robot
      assisted operation. The importance of HTA reports to evaluate new or established
      procedures will even increase in Germany especially in the recent medico-legal
      context.

PMID- 15977124
TI  - [Is the implantation of titanium stems in hip prostheses really obsolete?].
AB  - AIM: Due to several bad results of studies, titanium is no longer used as an
      implant material in cemented total hip arthroplasty. This study attempts figure
      out by means of a meta-analysis if the material titanium itself was responsible
      for the bad results of some studies or if specific implant characteristics
      contributed to implant failure, independent of titanium. METHOD: Studies between
      1960 and July 2002 were analysed concerning failure rates of cemented titanium
      total hip arthroplasties regarding their specific implant characteristics.
      RESULTS: Specific implant characteristics such as roughness of the surface and
      geometrical features led to significantly different failure rates. Stems of
      titanium with a dull surface and a wide proximal geometry could achieve such good
      results as those of the cobalt-chromium stems published in the study results of
      Malchau. CONCLUSION: Titanium is justified as a cementable material in total hip
      arthroplasty. By respecting specific implant characteristics, very good failure
      rates can be achieved. The high failure rates, published in several studies, are
      based upon implant characteristics which are not suitable for cementing
      techniques and not upon the implant material titanium itself.

PMID- 15977125
TI  - [Good results with a cemented titanium stem after 7-9 years].
AB  - AIM: Because of partially ver y controversial results in cemented hip stem
      replacements made of titanium alloy we investigated in our own patients the mid
      term survival of the "Euroform"-stem. This stem is anatomically designed for
      cemented fixation, made of Ti (6)Al (4)V. METHOD: Within a period between 1990
      and 2000 we implanted 2,141 Euroform-prostheses. The course of 103 patients which
      were operated between April 1990 and April 1992 was followed up. 9 patients died
      in the meantime and 8 could not be reached. Of the remaining 86 patients we could
      examine 73 patients with 79 prostheses (87 %). Investiagtion included a
      questionnaire and clinical and radiological examination to create the Harris-hip
      score. The follow-up was 7-9 years, with an average of 94 months. RESULT: Of
      those 79 prostheses, revision surgery was performed for septic loosening in three
      cases and for aseptic loosening in two cases. Radiologically one stem was found
      to be loosen. This means that for aseptic loosening we had a revision rate for
      aseptical femoral loosening of 2.5 % after 94 months with a mean Harris-hip-score
      of 84 points. Good or excellent results were found in 82 %, fair results in 9 %
      and poor results in 9 %. CONCLUSION: The "Euroform" prosthesis is a cemented
      titanium alloy stem that has in contrary to some other published studies good mid
      to long-term results.

PMID- 15977126
TI  - [Long-term results with the Harris-Galante press-fit-cup].
AB  - AIM: The present work aims at evaluating the clinical and radiological long-term
      results of the Harris-Galante press-fit cup. METHOD: At an average follow-up time
      of 9.5 years (min. 9, max. 10.3) 123 patients with 138 Harris-Galante press-fit
      cups (HGP) were examined clinically and radiology. The clinical evaluation was
      done with the Harris hip score. Together with the HGP, which was inserted in all
      cases, five different femoral stems were implanted. A lateral approach, according
      to the technique of Watson-Jones, was used in all cases. RESULTS: The mean follow
      up Harris hip score was 89 of 100 points and is assessed as a good result. 7 cups
      (5%) were classed as being radiological loose, but only one case had also
      clinical symptoms. A total of 10 cups (6.8%) had to be revised. 3 cups (2 %) had
      to be revised because of aseptic loosening. This result represents a survival
      rate of 93.2% according to Kaplan-Meier. CONCLUSION: The long-term clinical and
      radiological results of the Harris-Galante press-fit cup and there fixation
      method can assessed as good.

PMID- 15977127
TI  - [Design and first clinical results with the ZMR taper revision prosthesis].
AB  - AIM: The purpose of this study was to survey and to evaluate the first clinical
      and radiological results with the cementless ZMR taper hip prosthesis. METHOD:
      The modular distal-tapered stem was designed with a roughened titanium surface
      and sharp splines to achieve secure distal fixation and rotational stability. 90
      ZMR taper hip prostheses were implanted between October 1999 and July 2002. Out
      of these, 4 interventions were primary and 86 were revision procedures. In 43
      cases a complete hip prosthesis revision and in 43 cases a stem revision was
      necessary. The mean age of the 90 patients (42 males, 48 females) was 67.1 years.
      The mean follow-up period was 7.6 months (3 to 25 months). RESULTS: The stem
      displayed an excellent distal fixation. The mean subsidence could be measured
      with 4.3 mm. Furthermore, most cases showed a particularly favourable remodelling
      of the proximal femoral bone stock. Complications associated with revision
      included intraoperatively 4 femur fractures, 3 femur fissures, 5 femur
      perforations, 2 trochanter fractures and postoperatively 19 dislocations, 5
      superficial wound infections, 2 transient palsies, 1 pulmonary embolism, 1 stem
      rotation and 4 wound healing failures. Considering these complications 15 re
      revisions were necessary and the ZMR taper hip prosthesis had to be exchanged in
      3 cases. CONCLUSION: On the one hand the ZMR taper hip prosthesis proved its
      value, particularly with regard to the stem modularity, the excellent distal
      fixation in conjunction with the possibility of partial body weight bearing and
      the rapid bone remodelling of the femur. On the other hand an increased number of
      postoperative complications and re-revisions occurred. Further long-term studies
      seem to be essential.

PMID- 15977128
TI  - [Medical and cost efficiency of autologous blood donation in total hip or knee
      replacement].
AB  - AIM: Preoperative autologous blood donation before joint replacement has become
      standard practice. However, this procedure is discussed controversially regarding
      medical benefit and cost-effectiveness. METHOD: In a retrospective study the data
      of 994 patients scheduled for hip (THR) or knee arthroplasty (TKR) between 1/2000
      and 9/2002 were analysed. RESULTS: Altogether 612 patients donated autologous
      blood (61.6 %). 50.2 % of the patients got blood transfusions during surgery or
      in the course of their hospitalisation. Donors received blood units more often
      than non-donors (55.2 vs. 41.9 %). On average 1.4 +/- 1.7 blood units were given
      during or after THR and 0.8 +/- 1.1 units during or after TKR. Clear
      predispositions for an increased use of blood transfusions were cemented
      endoprosthesis, old age (> 70 years) as well as exclusive general anaesthesia.
      Since 57.8 % of the blood units were wasted, the additional expenses (only
      laboratory and material costs were calculated) for each retransfused autologous
      blood unit were calculated to be 28.76. CONCLUSION: Besides saving homologous
      blood, autologous blood donation causes mainly an increased probability of giving
      transfusions and higher costs. Therefore autologous blood donation should be
      indicated more critically, especially in younger patients and knee replacements.

PMID- 15977130
TI  - A preliminary study of the associations among preterm infant behaviors.
AB  - The purpose of this study was to examine whether relationships exist among
      various preterm infant behaviors. The study used an exploratory method design.
      Twenty infants were bathed and a total of 120 baths were video recorded and
      observed to measure preterm infant behaviors based on the frequency that
      behaviors occurred. The frequency was measured by using the preterm infant
      behavioral coding scheme developed for the study. Pearson Correlation
      Coefficients were used to analyze the behavioral data and examine whether the
      relationships among these behaviors were significant. The interrater reliability
      of the behavioral variables ranged from .82 to .99. There were highly positive
      correlations between the stress behaviors. There was, however, negative
      correlation between the stress behaviors and the stable behavior (sucking). The
      occurrences of the stress behaviors were associated with the state of " eyes open
      " and "fuss or crying". Knowing the associations may enhance NICU nurses '
      abilities to identify preterm infant behaviors. While interacting with preterm
      infants, nurses can sensitively and actively sense preterm infant signals,
      prevent or ameliorate the early threats to an infant ' s life, and adjust care to
      support the infant ' s growth and development.

PMID- 15977129
TI  - [Musculoskeletal biopsies in an open 0.5-T-MR system].
AB  - INTRODUCTION: MR-guided interventions have been successful in different medical
      disciplines. The aim of this paper is to report our results with the application
      of MR-guided biopsies of musculoskeletal lesions using an open 0.5-T-MR scanner
      and further to discuss these results on the basis of the available literature.
      PATIENTS AND METHODS: Between 1998 and 2003 30 patients (average age 44.1 years)
      underwent a total of 31 biopsies. The interventions were performed in an open 0.5
      T MRI system using an active optical localization system as well as a navigation
      system. For the motion tracking we used T (1)-weighted real-time sequences with
      0.25 pictures per second. For the sampling MR-compatible instruments were used
      that were specially developed for this purpose. The data of this retrospective
      investigation are based on the evaluation of the patient documents and the
      radiological findings. On the basis of the histological findings the technical
      success rate and the histological overall accuracy were determined. RESULTS: In
      81 % of the biopsies the histological diagnosis was correct. In cases of
      suspected inflammation the histological accuracy was smaller (70 %). No
      differences were observed between skeletal and soft-tissue lesions. The technical
      success rate amounted to 77.5 %. No procedural or anesthesiological complications
      occurred. The mean operating time amounted to 65 min including the time for
      motion tracking. DISCUSSION: In cases of suspected lesions of the musculoskeletal
      system, the MR-guided biopsy represents a promising and safe procedure to get a
      histological diagnosis. In cases of sufficient size of the lesion sampling of a
      representative probe is possible. On account of the outstanding performance in
      soft-part contrasting, the sensitive structures surrounding the lesion can be
      saved. Substantial disadvantages of the procedure are the high costs for personal
      and material and the long operating time.

PMID- 15977131
TI  - Frail elders' views of Tai Chi.
AB  - The beneficial effects of Tai Chi on an elder's well-being have been well
      documented; however, not many frail elders practice it. The purpose of this
      descriptive study was to explore the perspectives frail elders have about Tai
      Chi, including its movements, practice frequency and duration, and practice
      preferences. Using focus groups, 40 frail elders who lived in long-term care
      facilities were interviewed. Results indicated that Tai Chi styles with slow and
      large motions were manageable. Subjects preferred to practice Tai Chi in a group
      of 10 to 20 people, twice a week with 31 to 60 minutes of practice in the early
      morning or in the afternoon after napping. The practice locations should be wide,
      flat, non-disturbed, and well-ventilated. Tai Chi instructors should be
      experienced, gentle, considerate, and have clarity in expression. Findings can be
      used to design a simple Tai Chi program that is specifically tailored to the
      needs of frail elders.

PMID- 15977132
TI  - Effects of a weight-loss program for obese children: a "mix of attributes"
      approach.
AB  - Childhood obesity is an important global public health issue. There is a need for
      more effective, low cost and child-centered intervention programs for reducing
      body weight. In response to this need, we developed a mix of attributes approach
      (including content, interactivity, control, channel, and objectivity) to help
      obese children (weight-for-length index, WLI >/= 1.20) reduce their body weight
      and improve their knowledge, attitude, and behavior. The prevalence of obesity in
      our sample was 15.9 % (140 obese children out of 882 children studying in the
      fourth grade) . An experimental, randomized research design was conducted in this
      study. Anthropometric measurements (including Body Mass Index [BMI] , WLI, body
      fat percentage, triceps, and subscapular skinfold thickness) and questionnaires
      (including the Scale of Obesity and Body Weight Loss Knowledge, Attitude, and
      Practice) were evaluated at baseline (pretest) and after one month of the
      intervention (posttest) for all obese children. Of 140 obese children, 118
      completed this study (66 in the experimental group, 52 in the control group). The
      mix of attributes approach significantly reduced the degree of obesity revealed
      in anthropometric measurements. (p < .05). This approach also significantly
      improved obese children ' s knowledge (p < .001) and slightly improved their
      behaviors (p = .057); however, this program did not change the children ' s
      attitudes so easily (p = .597). To more effectively lose weight, we suggest an
      additional attribute, " individuality, " as a means of increasing efforts to
      change attitudes in obese children.

PMID- 15977133
TI  - Exploring the health-related quality of life among children with moderate asthma.
AB  - Asthma is one of the most common chronic diseases, impacting more than 10 % of
      children in Taiwan. The recurrent signs and symptoms and complexity of disease
      management impact the life quality of children with asthma. The purpose of this
      study was to describe the content and dimensions of health-related quality of
      life (HRQOL) among children with moderate asthma by descriptive qualitative
      research based on in-depth interviews. Eleven children, aged 6-12 years, and
      their mothers from two medical centers in central Taiwan were interviewed and
      tape recorded. The transcripts were analyzed using content analysis. Six themes
      relevant to the children's QOL with asthma were identified: 1. physical
      disturbances of signs/symptoms, 2. limitations of activity, 3. emotional
      distress, 4. discord in parent-child relationships, 5. restrictions in school
      social life and 6. daily inconvenience of managing the disease. These findings
      highlight the ways in which the overall quality of life of children is impacted
      by asthma including the physiological and psychosocial domains. The breadth of
      these findings may lead to greater insights into the nursing care of children
      with asthma.

PMID- 15977134
TI  - The experiences of overweight female adolescents after health promotion
      counseling.
AB  - The experiences of female overweight adolescents undergoing weight reduction are
      rarely reported. There is a paucity of studies using qualitative methodology to
      evaluate weight-reduction experiences. The aim of this study was to understand
      the main themes of the experiences of overweight female adolescents undergoing
      weight reduction after receiving school based health promotion counseling.
      Qualitative design was adopted and seven focus group discussions were conducted.
      On the basis of the qualitative method, the data were subjected to content
      analysis by means of the constant comparison method. A total of 30 female
      participants studying in a junior college of nursing were recruited in this
      study. All of them had been overweight or obese throughout the past four years.
      The findings revealed four themes of weight reduction experiences: living with
      changes; aspire vs. retreat; sense of alienation; support is a motivator. The
      outcomes of this study support the value of health promotion counseling conducted
      at school-based settings. It also provides references for health professionals
      promoting healthy ways of life.

PMID- 15977135
TI  - Home environmental hazards among community-dwelling elderly persons in Taiwan.
AB  - The purposes of this study were to determine the prevalence and variables that
      best predict home environmental hazards among the community-dwelling elderly in
      Taiwan. An assessment was made of the home environments of 1212 people aged 65
      years and older, chosen by cluster sampling from registered households in
      northern Taiwan. Environmental hazards were found in the majority of homes ( 60.4
      % ) where community-dwelling elderly people lived. The bathroom was the most
      common site for environmental hazards. Significant predictors of potential home
      environmental hazards were: living in an urban area ( OR = 4.36, 95 % confidence
      interval ( CI = 3.29, 5.76 ) , poor awareness of one ' s health status ( OR =
      1.86, 95 % CI = 1.31, 2.64 ) , family dysfunction ( OR = 1.77, 95 % CI = 1.21,
      2.59 ) , fear of falling ( OR = 1.65, 95 % CI = 1.19, 2.28 ) , being older ( >/=
      75 years, OR = 1.47, 95 % CI = 1.11, 1.96 ) , poor gait ( OR = 10.76, 95 % CI =
      4.48, 25.84 ) and poor balance ( OR = 3.03, 95 % CI = 1.14, 8.09 ) . Most elderly
      persons do not live in a risk-free home environment. The recognition and removal
      of environmental hazards is imperative to the well-being of the elderly.

PMID- 15977136
TI  - SARS: Key factors in crisis management.
AB  - This study was conducted at a single hospital selected in Taipei during the SARS
      (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan.
      During this period of time, 104 SARS patients were admitted to the hospital.
      There were no negative reports related to the selected hospital despite its being
      located right in the center of an area struck by the epidemic. The purpose of
      this study was to identify the key factors enabling the hospital to survive SARS
      unscathed. Data were collected from in-depth interviews with the nursing
      directors and nursing managers of the SARS units, along with a review of relevant
      hospital documents. The five key elements identified as survival factors during
      this SARS crisis are as follows: 1. good control of timing for crisis management,
      2. careful decision-making, 3. thorough implementation, 4. effective
      communication, and 5. trust between management and employees. The results of this
      study reconfirmed the selected hospital as a model for good crisis management
      during the SARS epidemic.

PMID- 15977137
TI  - Exploring the associations between long-term care and mortality rates among
      stroke patients.
AB  - Information on types of long-term care received by stroke patients after hospital
      discharge is essential for the formulation of long-term care resource development
      policy. Comparisons of outcomes resulting from different types of long-term care
      can provide important considerations in the selection of long- term care
      services. The purpose of this study is to describe the patterns of long-term care
      received, and to explore if associations exist between long-term care services
      and mortality status among stroke patients after hospital discharge. Using a
      longitudinal quasi-experimental study design, this study collected information on
      the type of long-term care received at 1, 3, and 6 months after discharge for 714
      patients. At one month after discharge, 4.5 % had died, and 22.1 % had regained
      all functions in activities of daily living and instrumental activities of daily
      living. The percentage of patients receiving institutional care, home or
      community-based care, and family care only were 10.4 % , 22.4 % , and 40.7 %
      respectively. The respective percentages at 3 months after discharge were 11.2 %
      , 18.7 % , and 38.0 % , and, at 6 months after discharge, 10.3 % , 19.4 % , and
      30.9 % . After adjusting for age, sex, previous incidence of stroke, and physical
      functions, the odds of dying within 6 months after discharge for stroke patients
      receiving home or community-based care was significantly lower than those in
      institutions ( OR = 0.39; 95 % CI = 0.15 to 0.97 ). It is not clear why a lower
      mortality rate was observed among patients receiving home or community-based
      services. Differences in quality of care and quality of life among users of
      different types of long-term care services should be investigated. More research
      is needed to assess the causes of the disparity in mortality rates among users of
      different types of long-term care services.

PMID- 15977138
TI  - Focal adhesion quantification - a new assay of material biocompatibility? Review.
AB  - The development of novel synthetic biomaterials is necessitated by the increasing
      demand for accelerated healing of tissues following surgical intervention. Strict
      testing of such materials is necessary before application. Currently, before any
      material can be marketed, approval by regulatory organisations such as the FDA is
      required. Presently, in vitro testing is performed as a prerequisite to in vivo
      evaluation. The in vitro techniques currently employed do not reflect the
      progress in our understanding of extra and intra-cellular processes, with far
      more sensitive in vitro evaluations now available. Obtaining quantifiable data is
      increasingly relevant to evaluating events occurring in vivo. Quantifying cell
      adhesion to surfaces provides some of this data as an initial assessment method.
      Major developments in this field are occurring but many investigators still use
      less than optimal methods for assessing biomaterials. The relevance of using cell
      adhesion assays to help determine biomaterial biocompatibility is reviewed.
      Additionally, current in vitro methods of evaluating biomaterials are discussed
      in the context of novel testing concepts developed by the authors.

PMID- 15977140
TI  - Uptake of radiolabelled modified fragment of human alfa-fetoptrotein by
      experimental mammary adenocarcinoma: in vitro and in vivo studies.
AB  - BACKGROUND: The aim of the study was to examine in vitro and in vivo binding of
      radiolabelled analogues of P149 peptide by experimental mammary adenocarcinoma
      with the intention of potential application for diagnosis and internal
      radiotherapy of tumours. MATERIAL AND METHODS: The 36-amino acid peptide (P149
      QY) of 90% homology to 447-480 peptide fragment of hAFP was synthesised and
      radiolabelled with iodine-125. The biodistribution of P149-Q[125I]-Y was studied
      in experimental mammary tumours. For in vitro experiments, extract from mouse
      mammary tumours were prepared and incubated with radioiodinated P149-QY peptide
      in the presence of a cross-linking reagent. RESULTS: The gel electrophoresis
      analysis (SDS-PAGE) showed that radioiodinated P149-QY peptide formed a complex
      with adenocarcinoma proteins of about 30 kDa. The biodistribution of P149-Q[125I]
      Y studied in experimental mammary tumours revealed a higher pharmacokinetic rate
      in comparison with the whole radioiodinated AFP molecule. A moderate uptake of
      P149-Q[125I]-Y in the tumour tissue was observed (3.2% ID/g at 30-min p.i.v).
      However, a faster radioactivity clearance from blood and normal tissues resulted
      in an increase in the tumour/muscle (T/M) ratio, i.e. from 2.3 to 3.4 after 30
      mins and 24 h p.i.v, respectively. CONCLUSIONS: The present study shows that
      radioiodinated P149-QY peptide reveals some positive features as the AFP receptor
      radioligand, however, some additional structural modifications of the initial
      peptide molecule are necessary for full retention of the ligand-receptor
      interaction of its radiolabelled forms.

PMID- 15977139
TI  - Uptake of radiolabelled endomorphins by experimental mammary adenocarcinoma.
AB  - BACKGROUND: The aim of this study was to examine the accumulation of endomorphin
      1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin- 2 (Tyr-Pro-Phe-Phe-NH2) labelled with
      radioiodine in tumour-bearing C3H/Bi mice. MATERIAL AND METHODS: Mice C3H/Bi
      bearing transplantable mammary adenocarcinoma were used as animal models to study
      the interaction between micro-opioid receptors and endomorphin-1 and 2. The
      expression of the micro-opioid receptor in the tumours was confirmed by cross
      linking assay and by RT- PCR technique. RESULTS: The endomorphins showed
      relatively high tumour accumulation - about 5.2% of dose/g tissue for endomorphin
      1 and about 3.8% for endomorphin-2. The ratio of tumour to muscle for endomorphin
      2 reached the highest value (12.7) six hours after injection. For endomorhin-1
      this ratio was the highest (7.5) three hours after injection. The cross-linking
      assay of [125I]-labelled peptides with membranes, isolated from the mouse
      adenocarcinoma, followed by electrophoresis and autoradiography revealed the
      presence of a radioactive complex with molecular weight of about 65 kDa. This
      complex was detectable by polyclonal antibodies raised against the N-terminal end
      of a micro-opioid receptor. The expression of gene encoding micro-opioid receptor
      on mouse mammary adenocarcinoma was further confirmed by RT-PCR technique. The
      binding studies with membranes of mouse mammary adenocarcinoma cells have shown
      significantly higher Bmax values for endomorphin-1 and endomorphin- 2 (806 and
      671, respectively) than for morphiceptin (131), a well-known specific micro
      opioid receptor ligand. CONCLUSIONS: Endomorphin-1 and 2 have shown a high
      affinity to the m-opioid receptor present in mouse mammary adenocarcinoma.
      However, endomorphin-2 showed more promising characteristics in biodistribution
      studies.

PMID- 15977141
TI  - Increase in utilization of myocardial perfusion imaging in the Czech Republic:
      activity and practice of nuclear cardiology, 2003.
AB  - BACKGROUND: The second survey of nuclear cardiology in the Czech Republic was
      conducted to ascertain whether the activity had increased since the first survey
      in 2001; we also intended to identify new trends in clinical practice. MATERIALS
      AND METHODS: All 46 departments of nuclear medicine in the Czech Republic
      completed a questionnaire concerning nuclear cardiology activity in 2002-2003 and
      current clinical and technical practices. RESULTS: There were 66 SPET cameras in
      2003 in comparison with 54 SPET cameras in 2001. Of the 46 centres, 39 (85%)
      provided nuclear cardiology service. The total number of cardiac studies was
      19,261 in 2003 (i.e. 1.9 studies/1,000 population; myocardial perfusion imaging
      (MPI) studies accounted for 91.3% of total nuclear cardiology. In 2001-2003, the
      utilization rate of MPI increased annually by 10%, 13% and 21% respectively.
      Twenty-six departments (67%) reported that the number of MPI had increased. The
      utilization of gated SPET method showed a very positive trend; as only 39% of all
      MPI studies were acquired using ECG-gating in 2001, but in 2003, there was an
      increase to 61%. We observed no increase in utilization of attenuation correction
      (3 centres in 2003 in comparison with 5 centres in 2001). Despite new PET
      capacity in the Czech Republic, the total number of FDG cardiology studies was
      somewhat lower in 2003 than in 2001 (155 compared with 163 studies). CONCLUSIONS:
      Our data documented substantial growth in the number of MPI examinations in 2001
      2003. However, Czech Republic nuclear cardiology activity still remained below
      the European average (2.2 studies/1,000 population in 1994); a further increase
      in MPI activity is necessary to adequately support the needs of cardiac patients.

PMID- 15977142
TI  - Reassessment of the reproducibility of Technetium-99m mercaptoacetyltriglycine
      clearance.
AB  - BACKGROUND: Conflicting results have been published concerning the
      reproducibility of Tc-99m MAG3 clearance. The aim of the study was to reevaluate
      again this reproducibility on a large prospective series of healthy volunteers.
      MATERIAL AND METHODS: Fifty subjects underwent three successive tests performed
      at 1-week interval. The physiological conditions were controlled as much as
      possible and all experimental measurements were rigorously double-checked. Renal
      clearances were calculated using single sample algorithms. RESULTS: Thin layer
      chromatography demonstrated a radiochemical purity of more than 92% (mean 93.8%;
      SD 1.6%; range 92.0-96.4%). The mean (and SD) of 44th minute plasma
      concentrations for the three successive measurements were respectively 1.8 +/-
      0.4, 2.1 +/- 0.4 and 1.9 +/- 0.4 (%dose/liter). The mean changes (and S.D. of
      differences) between two tests were 0.26 +/- 0.29, -0.08 +/- 0.5 and 0.18 +/-
      0.30 respectively between tests 1 and 2, tests 1 and 3, and tests 2 and 3. Using
      Bubeck's algorithm, the mean clearance values (ml/min/1.73 m2) were 268.8 (range
      201.4-336.8), 247.2 (range 170.5-290.3), and 262.8 (range 187.4-340.0)
      respectively for the first, second and third measurements. Using Russell's
      approach, the mean clearance values were respectively 314.9 (range: 208.7-441.7),
      280.1 (range: 167.5-358.6), and 305.4 (range: 189.5-447.9). CONCLUSIONS: High
      differences were observed between the 3 tests. Using Russell s formula, the SD of
      differences between two tests was respectively 35.8, 47.7 and 57.7 ml/min/1.73 m2
      between tests 1 and 2, tests 1 and 3, and tests 2 and 3. Whether such a large
      variability is acceptable in clinical practice depends solely on what the
      clinician is expecting.

PMID- 15977143
TI  - Diuresis renal scintigraphy "F-0" in diagnosing of upper urinary tract
      obstruction in children: the clinical significance.
AB  - BACKGROUND: The aim of this study was to assess the clinical relevance of
      diuresis renal scintigraphy after simultaneously administered radiopharmaceutical
      and diuretic (DRS "F-0") in diagnosing obstruction of upper urinary tract in
      children with previously documented hydronephrosis and ureterohydronephrosis,
      analyzing the value of qualitative and quantitative scintigraphy parameters.
      MATERIAL AND METHODS: This retrospective study enrolled 82 children (30 girls and
      52 boys aged between 2 months and 16 years; mean 5.8 +/- 4.5 years) with
      previously documented hydronephrosis or ureterohydronephrosis (42 left-sided, 28
      right-sided and 12 bilateral). DRS "F-0" was started after intravenous
      administration of diethylene-triamine- pentaacetic acid (DTPA) mixed with
      furosemide. Results of DRS "F-0" were analyzed qualitatively (visual analysis of
      scintigrams and renography curves) and quantitatively (time to reach maximum of
      the kidney curve-T max, washout of the tracer-WO, the furosemide clearance half
      time (F/2) and individual kidney function - IKF) and compared with the final
      diagnoses obtained in 37 children (42 nephroureteric units - NU) after surgery,
      in 41 children (48 NU) during the medical follow-up lasting at least 6 months,
      and in 4 children (4 NU) using invasive diagnostic procedures. Diagnostic
      criteria for obstructed NU (kidney with corresponding ureter) considered presence
      of pathological at least two of five scintigraphy variables characterized as a
      sign of obstruction. RESULTS: Forty true positive and 37 true negative results
      were detected using diagnostic criteria for obstructed and normal NU by means of
      DRS "F-0". DRS "F-0" failed to detect obstruction in 5 children with a total of 6
      obstructed NU, while the results were marked as false positive in 9 children (11
      NU). Qualitative scintigraphy analysis was found to be the most sensitive (91%)
      and accurate predictor (85%) in differentiating obstruction from non-obstructive
      renal unit. High sensitivity in predicting obstruction was also found for both
      washout of the radiopharmaceutical (87%) and for furosemide clearance half time
      (85%). Overall sensitivity of DRS "F-0" using proposed diagnostic criteria in
      differentiating obstruction was 87%, specificity 77% and accuracy 82%. However,
      DRS "F-0" has been shown to be more sensitive (90%) in children with UPJ and UVJ
      obstruction concerning children in whom obstruction was caused by other urinary
      tract diseases. CONCLUSION: This study showed DRS "F-0" as a sensitive and
      reliable method in diagnosing children with obstructions of the upper urinary
      tract. The great advantage of the protocol DRS "F-0" over other diuresis
      renography protocol modalities is due to the shorter time of the acquisition by
      half, and the avoidance of additional diuretic application. However, conventional
      quantitation of diuresis renogram did not improve the sensitivity and specificity
      with respect to the qualitative analysis of scintigrams and renography curves.

PMID- 15977144
TI  - Radioiodine treatment of hyperthyroidism in patients with low thyroid uptake.
AB  - BACKGROUND: The aim of the study was to analyze the effectiveness of radioactive
      131I in hyperthyroid patients with confirmed lowered iodine uptake as compared to
      patients with an uptake of over 30%. MATERIAL AND METHODS: We retrospectively
      analyzed 53 consecutive patients aged from 29 to 84 (mean age 60 years) suffering
      from hyperthyroidism caused by Graves' disease or toxic nodular goitre. The
      patients were divided into 2 sub-groups: the 1st with a maximum iodine uptake of
      18.7 +/- 3.2% (range, 11-23%) - 24 patients; the 2nd with a maximum iodine uptake
      of 27.1 +/- 2.1% (range, 24-30%) - 29 patients. The control group consisted of 50
      patients treated with 131I with an iodine uptake of over 30%. Each patient was
      evaluated before, and 6 months after, treatment for fT3, fT4 and TSH with ECLIA;
      TRAb with RIA; ultrasound with a 7.5 MHz linear probe. The volume of the thyroid
      gland was determined using the Gutekunst method. All these factors underwent
      statistical analysis and were considered along with the results of clinical
      examinations. RESULTS: Clinical remission of hyperthyroidism was evident in 79.3%
      of both sub-groups, in total (83.3% and 75.3%, respectively). TSH was normalized
      in 62.3% of these patients (54.2% and 69.0%, respectively). The mean range of TSH
      levels increased from 0.081 microU/ml to 4.0 microU/ml after therapy; that is,
      from 0.087 microU/ml to 4.97 microU/ml in the 1st sub-group and from 0.076
      microU/ml to 3.3 microU/ml in the 2nd sub-group. The volume of the thyroid gland
      was uniformly significantly lower, with a mean range of 40.5 ml before treatment
      and 21.7 ml afterwards. The results seen in both sub-groups were similar; only
      age and dose of radioiodine were slightly higher in the 1st, while mean uptake
      was higher in the 2nd. By comparison of these results to those of the control
      patients, we observed that the values of TSH, as well as thyroid volume and
      evidence of clinical remission, reflected those found in the control group. The
      mean dose of 131I was lower in the control group, that is 11.3 m Ci, as compared
      to the sub-groups as a whole, specifically, 15.7 mCi. The mean age of patients in
      the control group was slightly less than that of the study group (50.8 and 60,
      respectively). CONCLUSIONS: 1. The results of the treatment of patients with a
      low iodine uptake are similar to the results obtained in the group of patients
      with iodine uptake above 30% and therefore low iodine uptake should not be a
      contraindication for isotope I-131 therapy. 2. Additionally, we have demonstrated
      that a statistically significant decrease in thyroid volume is observed in all
      patients after the iodine isotope treatment which indirectly proves the
      effectiveness of the prescribed treatment, and that low thyroid iodine uptake is
      more frequently observed in elderly patients and in patients treated with iodine
      or anti-thyroid drugs.

PMID- 15977145
TI  - Lymphoedema: lymphoscintigraphy versus other diagnostic techniques--a clinician's
      point of view.
AB  - This paper overviews the problem of the clinical basis, diagnosis and available
      therapy modalities for lymphoedema. Regarding diagnostics, the measurement of
      circumference, volume and thickness of the limb are presented, as well as
      diagnostic imaging modalities. These include direct and indirect lymphography,
      MRI, CT, ultrasound imaging and lymphoscintigraphy, which is currently considered
      the leading technique in primary diagnosis of lymphoedema and its follow-up. This
      paper discusses the treatment of lymphoedema and the role of lymphoscintigraphy
      in the follow-up of patents with lymphoedema.

PMID- 15977146
TI  - Hepatic metastasis of differentiated thyroid carcinoma.
AB  - BACKGROUND: Differentiated thyroid cancers (DTC) often form metastases in neck
      lymph nodes, lungs and bones. Other metastases--to the brain, kidneys, skin and
      liver are rare. Liver metastases of DTC occur in the terminal phase of the
      disease and predominantly do not accumulate radioiodine. Functional (accumulating
      radioiodine) metastases are very rare. MATERIAL AND METHODS: In an 85 year old
      patient with DTC of the follicular type after removal of the thyroid and lymph
      nodes metastases on the neck and after the elimination of thyroid remnants by
      radioiodine, a functional metastasis in the liver was detected by combination of
      whole-body scintigraphy following administration of 131I and liver scintigraphy
      by using 99mTc-colloid, supplemented by bone scintigraphy after administration of
      99mTc-MDP. At first, the high thyroglobulin serum level was falsely negative
      after repeated radioiodine treatment. The patient was treated for this hepatic
      accumulating metastasis eight times by 59.2 GBq total dose of radioiodine.
      Radioiodine treatments were repeated for 7 years, the patient died at the age of
      92 years. CONCLUSIONS: It is necessary to distinguish between diffuse and focal
      radioiodine accumulation in a liver. Only a focal accumulation is characteristic
      for functional liver metastasis in which thyroxin synthesis is preserved. The
      correspondence of focal accumulation of radioiodine on whole-body scintigraphy
      with "cold" area on liver scintigraphy is specific for diagnosis of this
      metastasis. At the same time, it confirms the fact that radioiodine therapy can
      be both promising and successful, as we can see in the case of our patient.

PMID- 15977147
TI  - The usefulness of bone scannning for the diagnosis and evaluation of otogenic
      skull base osteomyelitis. A description of three cases.
AB  - BACKGROUND: The aim of this report was to assess the usefulness of bone scanning
      in the diagnosis and evaluation of the skull base osteomyelitis. MATERIAL AND
      METHODS: Bone scanning was performed in three male patients with otogenic skull
      base osteomyelitis, aged 65-84 years utilizing Tc99m-MDP and dual-head gamma
      camera. RESULTS: In one case, bone scanning played a crucial role in establishing
      the diagnosis. In two cases, it provided confirmed MRI results. CT scanning was
      negative in two cases. CONCLUSIONS: Bone scans may give valuable information for
      establishing the diagnosis and assessing the severity of this disease, and add
      complementary physiological information to radiological imaging.

PMID- 15977148
TI  - 99mTc-MDP uptake in fibrosarcoma in a cat.

PMID- 15977149
TI  - Healthcare systems in the European Union--an evaluation.

PMID- 15977150
TI  - Veterinary Nuclear Medicine again--commentary and remarks on: Krzeminski M et al.
      Veterinary nuclear medicine--a review. NMR 2004; 7: 177-182.

PMID- 15977155
TI  - Are antimicrobial peptides an alternative for conventional antibiotics?
AB  - Antimicrobial peptides are widespread in living organisms and constitute an
      important component of innate immunity to microbial infections. By the early
      1980s, more than 800 different antimicrobial peptides had been isolated from
      mammals, amphibians, fish, insects, plants and bacterial species. In humans, they
      are produced by granulocytes, macrophages and most epithelial and endothelial
      cells. Newly discovered antibiotics have antibacterial, antifungal, antiviral and
      even antiprotozoal activity. Occasionally, a single antibiotic may have a very
      wide spectrum of activity and may show activity towards various kinds of
      microorganisms. Although antimicrobial activity is the most typical function of
      peptides, they are also characterized by numerous other properties. They
      stimulate the immune system, have anti-neoplastic properties and participate in
      cell signalling and proliferation regulation. As antimicrobial peptides from
      higher eukaryotes differ structurally from conventional antibiotics produced by
      bacteria and fungi, they offer novel templates for pharmaceutical compounds,
      which could be used effectively against the increasing number of resistant
      microbes.

PMID- 15977159
TI  - Ligand-induced fit in mycobacterial MabA: the sequence-specific C-terminus locks
      the conformational change.
AB  - The protein MabA of Mycobacterium tuberculosis is a beta-ketoacyl reductase (KAR)
      and catalyses one of the four steps of the fatty acid elongation system FAS-II.
      The crystal structures of different KARs revealed a significant rearrangements of
      the active site between a "closed" inactive conformation and an "open" and active
      form in presence of the cofactor. MabA is a potential therapeutic target.
      However, only the structure of the "closed" form was obtained and rational drug
      design requires the structure of the active form. Here we described the sequences
      and structures analysis of the KARs to stabilize the "open form" in MabA. The
      crystal structure of a mutated MabA protein was then solved in both inactive and
      active form. The crystal structure of the wild-type MabA in the presence of NADP
      was also solved and showing a mixture of the two mutually exclusive
      conformations. This new structure of MabA is analyzed in view of its distinctive
      enzymatic and structural properties and those of related enzymes.

PMID- 15977160
TI  - Structure and energy landscape of a photoswitchable peptide: a replica exchange
      molecular dynamics study.
AB  - A replica exchange molecular dynamics (REMD) simulation of a bicyclic azobenzene
      peptide in explicit dimethyl sulfoxide solution is presented in order to
      characterize the conformational structures and energy landscape of a
      photoswitchable peptide. It is shown that an enhanced-sampling technique such as
      the REMD method is essential to obtain a converged conformational sampling of the
      peptide at room temperature. This is because conventional MD simulations of less
      than approximately 100-ns length are either trapped in local minima (at 295 K) or
      if run at high temperature-do not resemble the room-temperature REMD results.
      Calculating various nuclear Overhauser effects (NOEs) and (3)J-couplings, a good
      overall agreement between the REMD simulations and the NMR experiments of Renner
      et al. (Biopolymers 2000;54:501-514) is found. In particular, the REMD study
      confirms the general picture drawn by Renner et al. that the trans-isomer of the
      azobenzene peptide exhibits a well-defined structure, while the cis-isomer is a
      conformational heterogeneous system; that is, the trans-isomer occurs in 2 well
      defined conformers, while the cis-isomer represents an energetically frustrated
      system that leads to an ensemble of conformational structures. Employing a
      principal component analysis of the REMD data, the free energy landscape of the
      systems is studied at various temperatures. The implications for the folding and
      unfolding pathways of the system are discussed.

PMID- 15977161
TI  - Conditional expression of a myocardium-specific transgene in zebrafish transgenic
      lines.
AB  - To develop the first heart-specific tetracycline (Tet)-On system in zebrafish, we
      constructed plasmids in which the cardiac myosin light chain 2 promoter of
      zebrafish was used to drive the reverse Tet-controlled transactivator (rtTA) and
      the green fluorescent protein (GFP) reporter gene was preceded by an rtTA
      responsive element. In the zebrafish fibroblast cell-line, rtTA-M2, one of rtTA's
      derivatives, demonstrated the highest increase in luciferase activity upon
      doxycycline (Dox) induction. We then generated two germ lines of transgenic
      zebrafish: line T03 was derived from microinjection of a plasmid containing rtTA
      M2 and a plasmid containing a responsive reporter gene, whereas line T21 was
      derived from microinjection of a single dual plasmid. Results showed that line
      T21 was superior to line T03 in terms of greater GFP intensity after induction
      and with of minimal leakiness before induction. The photographic images of
      induced GFP in the heart of F2 larvae showed that the fluorescent level of GFP
      was dose-responsive. The level of GFP expressed in the F3 3 days
      postfertilization larvae that were treated with Dox for 1 hr decreased gradually
      after the withdrawal of the inducer; and the fluorescent signal disappeared after
      5 days. The GFP induction and reduction were also tightly controlled by Dox in
      the F3 adult fish from line T21. This Tet-On system developed in zebrafish shows
      much promise for the study of the gene function in a specific tissue at the later
      developmental stage.

PMID- 15977162
TI  - Oligonucleotide-based microarray analysis of retinoic acid target genes in the
      protochordate, Ciona intestinalis.
AB  - Oligonucleotide-based microarray analyses were carried out to identify retinoic
      acid target genes in embryos of the ascidian Ciona intestinalis. Of 21,938 spots,
      50 (corresponding to 43 genes) showed over twofold up-regulation in retinoic acid
      treated tail bud embryos. In situ hybridization verified retinoic acid-induced up
      regulation of 23 genes. Many of them were expressed in the anterior tail region,
      where a retinaldehyde dehydrogenase homolog is expressed. Homologs of vertebrate
      genes involved in neurogenesis and/or neuronal functions (e.g., COUP-TF, Ci-Hox1,
      and SCO-spondin) were expressed in the central nervous system of Ciona embryos,
      and activated by retinoic acid. Genes encoding transcription factors (e.g., Ci
      lmx1.2, vitamin D receptor, and Hox proteins) and apoptosis-related proteins
      (e.g., transglutaminase and an apoptosis-inducing factor homolog) were also
      activated by retinoic acid. Simultaneous treatment of embryos with retinoic acid
      and puromycin revealed a few direct targets, including genes encoding Ci-Hox1, Ci
      Cyp26, and an Rnf126-like ring finger protein.

PMID- 15977163
TI  - Glial and neuronal connexin expression patterns in the rat spinal cord during
      development and following injury.
AB  - Spinal cord injury induces a complex cascade of degenerative and remodeling
      events evolving over time. The possible roles of changed intercellular
      communication via gap junctions after spinal cord injury (SCI) have remained
      relatively unexplored. We investigated the temporospatial expression patterns of
      gap junctional genes and proteins, connexin 43 (Cx43), Cx36, and Cx32, by in situ
      hybridization and immunohistochemistry in the rat neonatal, adult normal, and
      adult injured spinal cord. Cx36 was strongly expressed in immature neurons, and
      levels declined markedly during development, whereas Cx43 and Cx32 persisted
      throughout adulthood. After a complete transection of the adult spinal cord, the
      levels of Cx43 mRNA and protein were up-regulated within hours, especially in
      gray matter rostral to the lesion, reaching over three times normal levels at 4
      weeks postinjury. Cx43 immunoreactivity was seen primarily in astrocytes and
      rarely in microglia. In contrast, Cx36 and Cx32 mRNA and proteins were relatively
      sparse and unchanged after spinal cord injury along the entire axis of the spinal
      cord. Cx43 is the most abundant gap junctional protein in the adult CNS and has
      been shown to form channels between astrocytes as well as between astrocytes and
      oligodendrocytes. Long-term up-regulation of Cx43 in reactive astrocytes may be
      one critical component in the rearrangement of the local astroglial network
      following SCI.

PMID- 15977164
TI  - TrkB expression and phospho-ERK activation by brain-derived neurotrophic factor
      in rat spinothalamic tract neurons.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin implicated in the
      phenomena of synaptic plasticity in the adult. It is found in terminals of
      nociceptive primary afferents. Following a pain-related stimulus, it is released
      in the spinal cord, where it activates its high-affinity receptor TrkB, leading
      to the phosphorylation of the mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase (ERK). A large body of evidence suggests
      that BDNF has a positive neuromodulatory effect on glutamate transmission in the
      spinal cord. However, none of these studies examined anatomically whether
      projection neurons known to be involved in transmission of nociceptive inputs
      express BDNF's receptor. Because the spinothalamic tract (STT) is a well
      characterized pathway for its role in the transfer and integration of sensory and
      nociceptive informations, this study in rats aimed to 1) determine whether
      neurons of the STT pathway express the TrkB receptor, 2) establish the
      rostrocaudal and laminar distribution of STT-TrkB neurons in the whole spinal
      cord, and 3) test the potential functionality of TrkB expression in these cells
      by investigating the ability of BDNF to activate the MAP kinase ERK. Using tract
      tracing coupled to immunofluorescent labeling for TrkB, we observed that in all
      levels of the spinal cord most STT neurons were immunoreactive for TrkB.
      Furthermore, microinjections of BDNF into the spinal cord or release of
      endogenous BDNF by intraplantar injection of capsaicin activated ERK
      phosphorylation in TrkB-containing STT neurons. These data suggest an important
      role for BDNF in nociception as an activator of spinothalamic projection neurons.

PMID- 15977166
TI  - Cell birth and death in the mouse retinal ganglion cell layer.
AB  - Here we describe quantitatively the birth and death of the two separate
      populations of neurons, ganglion cells and displaced amacrine cells, in the mouse
      retinal ganglion cell layer (GCL). The two cell types, which are roughly equally
      numerous, were distinguished pre- and postnatally by labeling the ganglion cells
      retrogradely with fluorescent dye. Embryos were labeled cumulatively with
      bromodeoxyuridine (BrdU) delivered by an osmotic minipump implanted in the
      mother; cell birth dates were established as having occurred before or after pump
      implantation. Early cohorts (GCL cells born before embryonic day [E] 11.8 and
      E12.8) were 98+/-1.1% and 99+/-0.2% ganglion cells (mean+/-SEM), respectively,
      and a late cohort (born after E15.8) was 97+/-1.2% displaced amacrines. Thus
      birth date was a strong predictor of a GCL cell's ultimate identity. Cell death
      in each cohort was estimated by counting cells at different time points (soon
      after the cohort was produced and later) and subtracting the later from the
      earlier number. This method avoids the problem of simultaneous birth and death
      that has plagued many of the earlier attempts to assess cell death. Negligible
      numbers died during the first week after a cell's birthday. The amount of cell
      death differed in the two cohorts; 48.5+/-15% and 29.0+/-12.4% in early and late,
      respectively, and most of it was postnatal. These findings disagree sharply with
      an earlier conclusion that ganglion cells die within 5 days of their birthdays or
      not at all.

PMID- 15977165
TI  - Central amygdala in anuran amphibians: neurochemical organization and
      connectivity.
AB  - The evolution of the amygdaloid complex in tetrapods is currently under debate on
      the basis of new neurochemical, hodological, and gene expression data. The anuran
      amygdaloid complex, in particular, is being examined in an effort to establish
      putative homologies with amniotes. The lateral and medial amygdala, comparable to
      their counterparts in amniotes, have recently been identified in anurans. In the
      present study we characterized the autonomic portion of the anuran amygdala, the
      central amygdala (CeA). First, the distribution of several neuronal markers
      (substance P, neuropeptide Y, somatostatin, tyrosine hydroxylase, and nitric
      oxide synthase) was analyzed. The localization of immunoreactive cells, primarily
      nitrergic cells, and the topographically arranged fiber labeling for all markers
      characteristically identified the CeA. Subsequently, the afferent and efferent
      connections of the CeA were investigated by means of in vivo and in vitro tracing
      techniques with dextran amines. The anuran CeA was revealed as the main component
      of the amygdaloid autonomic system, showing important connections with brainstem
      centers such as the parabrachial nucleus and the nucleus of the solitary tract.
      Only scarce CeA-hypothalamic projections were observed, whereas bidirectional
      connections between the CeA and the lateral and medial amygdala were abundant.
      The present neurochemical and hodological results support the homology of the
      anuran CeA with its counterpart in amniotes and strengthen the idea of a
      conserved amygdaloid organization in the evolution of tetrapods.

PMID- 15977167
TI  - Expression of GABA(B) receptor in the avian auditory brainstem: ontogeny,
      afferent deprivation, and ultrastructure.
AB  - Nucleus magnocellularis (NM), nucleus angularis (NA), and nucleus laminaris (NL),
      second- and third-order auditory neurons in the avian brainstem, receive
      GABAergic input primarily from the superior olivary nucleus (SON). Previous
      studies have demonstrated that both GABA(A) and GABA(B) receptors (GABA(B)Rs)
      influence physiological properties of NM neurons. We characterized the
      distribution of GABA(B)R expression in these nuclei during development and after
      deafferentation of the excitatory auditory nerve (nVIII) inputs. We used a
      polyclonal antibody raised against rat GABA(B)Rs in the auditory brainstem during
      developmental periods that are thought to precede and include synaptogenesis of
      GABAergic inputs. As early as embryonic day (E)14, dense labeling is observed in
      NA, NM, NL, and SON. At earlier ages immunoreactivity is present in somas as
      diffuse staining with few puncta. By E21, when the structure and function of the
      auditory nuclei are known to be mature, GABA(B) immunoreactivity is characterized
      by dense punctate labeling in NM, NL, and a subset of NA neurons, but label is
      sparse in the SON. Removal of the cochlea and nVIII neurons in posthatch chicks
      resulted in only a small decrease in immunoreactivity after survival times of 14
      or 28 days, suggesting that a major proportion of GABA(B)Rs may be expressed
      postsynaptically or on GABAergic terminals. We confirmed this interpretation with
      immunogold TEM, where expression at postsynaptic membrane sites is clearly
      observed. The characterization of GABA(B)R distribution enriches our
      understanding of the full complement of inhibitory influences on central auditory
      processing in this well-studied neuronal circuit.

PMID- 15977168
TI  - Cloning and expression analysis of retinoic acid receptors in the zebra finch
      brain.
AB  - The vitamin A derivative retinoic acid is produced postembryonically in discrete
      portions of the songbird brain, including some of the nuclei involved in song
      production and song learning, and its synthesis is required for the normal
      maturation of song behavior. To identify the brain targets for retinoic acid
      action, we cloned the zebra finch homologs of the alpha, beta, and gamma classes
      of retinoic acid receptors (RARs). In situ hybridization analysis revealed that
      the mRNAs for all three RARs are expressed at different levels in several brain
      areas, with a broader distribution than the mRNA for retinaldehyde-specific
      aldehyde dehydrogenase (zRalDH), a retinoic acid-synthesizing enzyme. Detectable
      RAR expression was found in all nuclei of the song control system, with the most
      marked expression occurring within the striatal song nucleus area X. These
      observations are consistent with a persistent action of retinoic acid in the
      postembryonic and adult songbird brain and provide further evidence for an
      involvement of retinoic acid signaling in the control of learned vocal behavior
      in a songbird species. They also suggest that the striatum is a major target of
      retinoic acid in songbirds.

PMID- 15977169
TI  - Ontogeny of bidirectional connections between the medial nucleus of the amygdala
      and the principal bed nucleus of the stria terminalis in the rat.
AB  - Nuclei in the amygdala and bed nuclei of the stria terminalis (BST) form
      functionally organized units that are linked by topographically organized
      connections. The posterodorsal part of the medial nucleus of the amygdala (MEApd)
      and the principal nucleus of the BST (BSTpr) share strong birectional connections
      that project primarily through the stria terminalis. The presence of structural
      and neurochemical sexual dimorphisms in both the MEApd and BSTpr suggests that
      connections between the nuclei may develop during the postnatal critical period
      for sexual differentiation. In this study, 1,1'dioctadecyl-3,3,3'
      tetramethylindocarbocyanine perchlorate (DiI) axonal labeling was used to define
      the ontogeny of this bidirectional pathway. Placement of DiI crystals into the
      MEApd of rats perfused on embryonic day (E) 20 resulted in DiI-labeled fibers
      with axonal morphology in the BSTpr, but similar labeling was not evident in the
      MEApd until after birth. However, as early as E14, tracer implants into the
      caudal MEA (the presumptive MEApd) labeled elongated cellular processes in the
      region of the stria terminalis that extended into the presumptive BSTpr. Based on
      the correspondence of these DiI-labeled processes with immunostaining for
      vimentin, these cellular processes are probably derived from glial cells.
      Implants of DiI into the posterior BST also labeled cellular processes that
      extended through the medial part of the stria terminalis, but they remained
      confined to the molecular layer of the MEApd from E14 through P1. Labeled axons
      derived from the BSTpr were not observed in the MEApd until P5, demonstrating
      that the bidirectional connections that exist between the MEApd and BSTpr in
      mature rats do not develop simultaneously. The density of connections between the
      BSTpr and MEApd increased during the postnatal period and was similar to that of
      adults by P15. These findings suggest that projections from the MEApd through the
      stria terminalis to the BSTpr may be specified initially by a glial substrate and
      that return projections to the amygdala from the BSTpr develop secondary to its
      innervation by the MEApd.

PMID- 15977170
TI  - Calcitonin gene-related peptide-containing pathways in the rat forebrain.
AB  - The present study focuses on the topographical distribution of calcitonin gene
      related peptide (CGRP)-containing cell bodies and fibers and their connections
      and pathways in the rat forebrain. We confirm previously reported CGRP
      projections from the perifornical area of the hypothalamus to the lateral septum,
      from the posterior thalamus to the caudate putamen and cerebral cortex, and from
      the parabrachial nuclei to the central extended amygdala, lateral hypothalamus,
      and ventromedial thalamus. Despite previous descriptions of CGRP in the central
      nervous system, important neuroanatomical aspects of the forebrain CGRP system
      remained obscure, which we addressed by using brain lesion techniques combined
      with modern immunohistology. We first report CGRP terminal fields in the
      olfactory-anterior septal region and also CGRP projections from the parabrachial
      nuclei to the olfactory-anterior septal region, the medial prefrontal cortex, the
      interstitial nucleus of the anterior commissure, the nucleus of the lateral
      olfactory tract, the anterior amygdaloid area, the posterolateral cortical
      amygdaloid nucleus, and the dorsolateral part of the lateral amygdaloid nucleus.
      In addition, we identified a CGRP cell group in the premamillary nuclei and
      showed that it projects to the medial CGRP layer of the lateral septum. CGRP
      fibers usually join other pathways rather than forming bundles. They run along
      the fornix from the hypothalamus, along the supraoptic decussations or the
      inferior thalamic peduncle-stria terminalis pathway from the posterior thalamus,
      and along the superior cerebellar peduncle, thalamic fasciculus, and ansa
      peduncularis from the parabrachial nuclei. This description of the forebrain CGRP
      system will facilitate investigation of its role in higher brain functions.

PMID- 15977171
TI  - Experimental analyses of the function of the proepicardium using a new
      microsurgical procedure to induce loss-of-proepicardial-function in chick
      embryos.
AB  - The proepicardium (PE) is a primarily extracardiac progenitor cell population
      that colonizes the embryonic heart and delivers the epicardium, the subepicardial
      and intramyocardial fibroblasts, and the coronary vessels. Recent data show that
      PE-derived cells additionally play important regulatory roles in myocardial
      development and possibly in the normal morphogenesis of the heart. Developmental
      Dynamics 233, 2005. Research on the latter topics profits from the fact that loss
      of-PE-function can be experimentally induced in chick embryos. So far, two
      microsurgical techniques were used to produce such embryos: (1) blocking of PE
      cell transfer with pieces of the eggshell membrane, and (2) mechanical excision
      of PE. Both of these techniques, however, have their shortcomings. We have
      searched, therefore, for new techniques to eliminate the PE. Here, we show that
      loss-of-PE-function can be induced by photoablation of the PE. Chick embryos were
      treated in ovo by means of a window in the eggshell at Hamburger and Hamilton
      (HH) stage 16 (iday 3). The pericardial coelom was opened, and the PE was
      externally stained with a 1% solution of Rose Bengal by means of a micropipette.
      Photoactivation of the dye was accomplished by illumination of the operation
      field with visible light. Examination on postoperative day 1 (iday 4, HH stages
      19/20) disclosed complete removal of PE in every experimental embryo. On iday 9
      (HH stages 33/34), the survival rate of experimental embryos was 35.7% (15 of
      42). Development of the PE-derivatives was compromised in the heart of every
      survivor. The abnormalities encompassed hydro- or hemopericardium, epicardium
      free areas with aneurysmatic outward bulging of the ventricular wall, thin
      myocardium, defects of the coronary vasculature, and abnormal tissue bridges
      between the ventricles and the pericardial wall. Our results show that
      photoablation of the PE is a powerful technique to induce long-lasting loss-of-PE
      function in chick embryos. We have additionally obtained new data that suggest
      that the embryonic epicardium may make important contributions to the passive
      mechanics of the developing heart.

PMID- 15977172
TI  - Induction of initial cardiomyocyte alpha-actin--smooth muscle alpha-actin--in
      cultured avian pregastrula epiblast: a role for nodal and BMP antagonist.
AB  - During early cardiogenesis, endoderm-derived bone morphogenetic protein (BMP)
      induces the expression of both heart-specific transcription factors and
      sarcomeric proteins. However, BMP antagonists do not inhibit the expression of
      the "initial heart alpha-actin"--smooth muscle alpha-actin (SMA)--which is first
      expressed in the anterior lateral mesoderm and then recruited into the initial
      myofibrils (Nakajima et al. [2002] Dev. Biol. 245:291-303). Therefore, mechanisms
      that regulate the expression of SMA in the heart-forming mesoderm are not well
      understood. Regional explantation experiments using chick blastoderm showed that
      the posterolateral region of the epiblast differentiated into cardiomyocytes.
      Posterior epiblast cultured with or without the associated hypoblast showed that
      interaction between the tissues of these two germ layers at the early pregastrula
      stage (stages X-XI) was a prerequisite for the expression of SMA. Posterior
      epiblast that is cultured without hypoblast could also be induced to express SMA
      if TGF-beta or activin was added to the culture medium. However, neither
      neutralizing antibodies against TGF-betas nor follistatin perturbed the
      expression of SMA in cultured blastoderm. Adding BMP to the cultured blastoderm
      inhibited the expression of SMA, whereas BMP antagonists, such as chordin, were
      able to induce the expression of SMA in cultured posterior epiblast. Furthermore,
      adding lefty-1, a nodal antagonist, to the blastoderm inhibited the expression of
      SMA, and nodal plus BMP antagonist up-regulated the expression of SMA in cultured
      posterior epiblast. Results indicate that the interaction between the tissues of
      the posterior epiblast and hypoblast is necessary to initiate the expression of
      SMA during early cardiogenesis and that nodal and BMP antagonist may play an
      important role in the regulation of SMA expression.

PMID- 15977173
TI  - LOVD: easy creation of a locus-specific sequence variation database using an
      "LSDB-in-a-box" approach.
AB  - The completion of the human genome project has initiated, as well as provided the
      basis for, the collection and study of all sequence variation between
      individuals. Direct access to up-to-date information on sequence variation is
      currently provided most efficiently through web-based, gene-centered, locus
      specific databases (LSDBs). We have developed the Leiden Open (source) Variation
      Database (LOVD) software approaching the "LSDB-in-a-Box" idea for the easy
      creation and maintenance of a fully web-based gene sequence variation database.
      LOVD is platform-independent and uses PHP and MySQL open source software only.
      The basic gene-centered and modular design of the database follows the
      recommendations of the Human Genome Variation Society (HGVS) and focuses on the
      collection and display of DNA sequence variations. With minimal effort, the LOVD
      platform is extendable with clinical data. The open set-up should both facilitate
      and promote functional extension with scripts written by the community. The LOVD
      software is freely available from the Leiden Muscular Dystrophy pages
      (www.DMD.nl/LOVD/). To promote the use of LOVD, we currently offer curators the
      possibility to set up an LSDB on our Leiden server.

PMID- 15977174
TI  - Evaluation of the molecular mechanisms involved in the gain of function of a Li
      Fraumeni TP53 mutation.
AB  - The TP53 tumor suppressor gene is the most frequent target for genetic
      alterations in human cancer. TP53 gene alterations may result in the gain of
      oncogenic functions such as neoangiogenesis and resistance to therapy. The TP53
      germ line mutation c.659A>C (p.Y220S) was identified in stored DNA from related
      patients with Li-Fraumeni syndrome (LFS) who died after developing clinically
      aggressive tumors. All of the patients were treated with protocols that included
      doxorubicin hydrochloride (DX) as a pivotal drug. To define the in vitro
      mutational phenotype of this germ line mutation, we used murine fibroblasts
      explanted from wild-type (wt) and p53 knockout (KO) mice from the same
      littermate. p53Y220S and p53R175H fibroblasts, obtained from p53KO fibroblasts
      transfected with expression vectors encoding the human Y220S and R175H p53
      mutants, respectively, exhibited resistance to DX treatment. Moreover, p53Y220S
      fibroblasts exhibited angiogenetic properties, and after DX treatment, p53Y220S
      failed to translocate into the nucleus and showed an increase in its cytosolic
      levels. DX treatment does not influence p53 distribution within the nuclear and
      cytosolic compartments in p53R175H fibroblasts. Peroxiredoxin II (Prx II), a
      protein that is involved in eliminating reactive oxygen species (ROS), showed
      increased expression intensity in p53Y220S fibroblasts after DX treatment, as
      observed by two-dimensional electrophoresis analysis. Moreover, Thioredoxin
      (Trx), a protein that cooperates with Prx II, is overexpressed in p53Y220S
      mutants under basal conditions. These data suggest a relationship between the
      presence of the p53Y220S mutation and enhanced levels of Prx II and Trx in mutant
      fibroblasts. Since one of the mechanisms of the DX antitumor effect has been
      ascribed to production of ROS, future studies will evaluate the involvement of
      PrxII and Trx in the chemoresistance of p53Y220S fibroblasts to DX.

PMID- 15977175
TI  - Zebrafish acvr2a and acvr2b exhibit distinct roles in craniofacial development.
AB  - To examine the roles of activin type II receptor signaling in craniofacial
      development, full-length zebrafish acvr2a and acvr2b clones were isolated.
      Although ubiquitously expressed as maternal mRNAs and in early embryogenesis, by
      24 hr postfertilization (hpf), acvr2a and acvr2b exhibit restricted expression in
      neural, hindbrain, and neural crest cells (NCCs). A morpholino-based targeted
      protein depletion approach was used to reveal discrete functions for each acvr2
      gene product. The acvr2a morphants exhibited defects in the development of most
      cranial NCC-derived cartilage, bone, and pharyngeal tooth structures, whereas
      acvr2b morphant defects were largely restricted to posterior arch structures and
      included the absence and/or aberrant migration of posterior NCC streams, defects
      in NCC-derived posterior arch cartilages, and dysmorphic pharyngeal tooth
      development. These studies revealed previously uncharacterized roles for acvr2a
      and acvr2b in hindbrain and NCC patterning, in NCC derived pharyngeal arch
      cartilage and joint formation, and in tooth development.

PMID- 15977176
TI  - JAM-A expression during embryonic development.
AB  - Cell adhesion molecules of the immunoglobulin superfamily play an important role
      in embryonic development. We have shown recently that JAM-A, a member of this
      family expressed at endothelial and epithelial tight junctions, is involved in
      platelet activation, leukocyte transmigration, and angiogenesis. Here, we
      determine the expression pattern of the JAM-A gene during embryogenesis using
      transgenic mice expressing lacZ under the control of the endogenous JAM-A
      promoter. Histochemical staining for beta-galactosidase in heterozygous mouse
      embryos was first seen in the inner cell mass and trophectoderm of the
      blastocyst. By 8.5 days post coitum (dpc), JAM-A gene activity was detected in
      the endoderm and part of the surface ectoderm. At 9.5 dpc, JAM-A expression began
      to localize to certain organ systems, most notably the developing inner ear and
      early vasculature. Localization of JAM-A to embryonic vasculature was confirmed
      by double-staining with antibodies against JAM-A and platelet endothelial cell
      adhesion molecule-1, a known endothelial cell marker. As organogenesis
      progressed, high levels of JAM-A expression continued in the epithelial component
      of the inner ear as well as the epithelium of the developing skin, olfactory
      system, lungs, and kidneys. In addition, JAM-A gene activity was found in the
      developing liver, choroid plexuses, and gut tubes. Immunofluorescent staining
      with a JAM-A antibody was performed to confirm that expression of the JAM-A-beta
      galactosidase fusion protein accurately represented endogenous JAM-A protein.
      Thus, JAM-A is prominently expressed in embryonic vasculature and the epithelial
      components of several organ systems and may have an important role in their
      development.

PMID- 15977177
TI  - Embryonic expression of murine 5T4 oncofoetal antigen is associated with
      morphogenetic events at implantation and in developing epithelia.
AB  - Overexpression of 5T4 oncofoetal antigen, an early marker of ES cell
      differentiation, in vitro increases cellular motility and decreases adhesion,
      properties relevant to development and cancer. Embryonic expression of m5T4
      antigen is first detected on trophectoderm at implantation and is restricted to
      extra-embryonic tissues to embryonic day (E) 11.5. In the embryo, significant
      m5T4 expression is detected at E12.5 in hindbrain roofplate and in various
      epithelia derived from all germ layers. In keratin 14-expressing epithelia, there
      is a congruent 5T4 expression pattern with many of these cells being Ki-67
      positive. In brain, expression is observed in roofplate, ependymal layers,
      choroid plexus, and subventricular zones of lateral ventricles at E14.5. By
      E17.5, expression is decreased in the subventricular zone with further
      restriction to choroid plexus in adult brain. Our data demonstrate a limited 5T4
      expression profile during embryogenesis associated with actively cycling,
      undifferentiated epithelial progenitor cells that may contribute to their
      migration.

PMID- 15977178
TI  - Complex gene rearrangements caused by serial replication slippage.
AB  - The now-classical model of replication slippage can in principle account for both
      simple deletions and tandem duplications associated with short direct repeats.
      Invariably, a single replication slippage event is invoked, irrespective of
      whether simple deletions or tandem duplications are involved. However, we
      recently identified three complex duplicational insertions that could also be
      accounted for by a model of serial replication slippage. We postulate that a
      sizeable proportion of hitherto inexplicable complex gene rearrangements may be
      explained by such a model. To test this idea, and to assess the generality of our
      initial findings, a number of complex gene rearrangements were selected from the
      Human Gene Mutation Database (HGMD). Some 95% (20/21) of these mutations were
      found to be explicable by twin or multiple rounds of replication slippage, the
      sole exception being a double deletion in the F9 gene that is associated with DNA
      sequences that appear capable of adopting non-B conformations. Of the 20 complex
      gene rearrangements, 19 (seven simple double deletions, one triple deletion, two
      double mutational events comprising a simple deletion and a simple insertion, six
      simple indels that may constitute a novel and non-canonical class of gene
      conversion, and three complex indels) were compatible with the model of serial
      replication slippage in cis; the remaining indel in the MECP2 gene, however,
      appears to have arisen via interchromosomal replication slippage in trans. Our
      postulate that serial replication slippage may account for a variety of complex
      gene rearrangements has therefore received broad support from the study of the
      above diverse series of mutations.

PMID- 15977179
TI  - dbQSNP: a database of SNPs in human promoter regions with allele frequency
      information determined by single-strand conformation polymorphism-based methods.
AB  - We present a database, dbQSNP (http://qsnp.gen.kyushu-u.ac.jp/), that provides
      sequence and allele frequency information for single-nucleotide polymorphisms
      (SNPs) located in the promoter regions of human genes, which were defined by the
      5' ends of full-length cDNA clones. We searched for the SNPs in these regions by
      sequencing or single-strand conformation polymorphism (SSCP) analysis. The allele
      frequencies of the identified SNPs in two ethnic groups were quantified by SSCP
      analyses of pooled DNA samples. The accuracy of our estimation is supported by
      strong correlations between the frequencies in our data and those in other
      databases for the same ethnic groups. The frequencies vary considerably between
      the two ethnic groups studied, suggesting the need for population-based
      collections and allele frequency determination of SNPs, in, e.g., association
      studies of diseases. We show profiles of SNP densities that are characteristic of
      transcription start site regions. A fraction of the SNPs revealed a significantly
      different allele frequency between the groups, suggesting differential selection
      of the genes involved.

PMID- 15977180
TI  - Macroarray-based analysis of tail regeneration in Xenopus laevis larvae.
AB  - Xenopus larvae possess a remarkable ability to regenerate their tails after they
      have been severed. To gain an understanding of the molecular mechanisms
      underlying tail regeneration, we performed a cDNA macroarray-based analysis of
      gene expression. A Xenopus cDNA macroarray representing 42,240 independent clones
      was differentially hybridized with probes synthesized from the total RNA of
      normal and regenerating tails. Temporal expression analysis revealed that the up
      regulated genes could be grouped into early or late responding genes. A
      comparative expression analysis revealed that most genes showed similar
      expression patterns between tail development and regeneration. However, some
      genes showed regeneration-specific expression. Finally, we identified 48 up
      regulated genes that fell into several categories based on their putative
      functions. These categories reflect the various processes that take place during
      regeneration, such as inflammation response, wound healing, cell proliferation,
      cell differentiation, and control of cell structure. Thus, we have identified a
      panel of genes that appear to be involved in the process of regeneration.

PMID- 15977181
TI  - Isolation of arterial-specific genes by subtractive hybridization reveals
      molecular heterogeneity among arterial endothelial cells.
AB  - Arteries are distinguished from veins by differences in gene expression, as well
      as in their anatomy and physiology. The characterization of arterial- and venous
      specific genes may improve our understanding of cardiovascular development and
      disease. Here we report the results of a subtractive hybridization screen for
      arterial-specific genes, and describe in detail the expression of a novel
      arterial-specific gene, Depp (decidual protein induced by progesterone), using a
      GFP-Cre knock-in that permits a comparison of both instantaneous and cumulative
      expression patterns in situ. Several features of Depp expression are noteworthy.
      First, Depp is expressed in endothelial cells of peripheral tissues, but not in
      atrial or ventricular endocardial cells of the heart. Very few genes have been
      reported to discriminate between these two cell types, and therefore this
      specificity may be useful in generating conditional mutations in other genes
      implicated in cardiovascular development. Second, Depp reveals an unexpected
      degree of molecular heterogeneity among arterial endothelial cells. Third, Depp
      is up-regulated in subsets of endothelial cells, in settings of adult neo
      vascularization, including tumor angiogenesis. Taken together, these data reveal
      unanticipated temporal and spatial heterogeneity among arterial endothelial cells
      of various tissues and organs, raising new questions regarding the functional
      significance of this diversity.

PMID- 15977182
TI  - Joint development in Xenopus laevis and induction of segmentations in
      regenerating froglet limb (spike).
AB  - In Xenopus laevis, amputation of the adult limb results in the formation of a
      simple (hypomorphic) spike-like structure without joints, although tadpole limb
      bud regenerates complete limb pattern. The expression of some joint marker genes
      was examined in limb development and regeneration. Bmp-4 and gdf-5 were expressed
      and sox-9 expression was decreased in the joint region. Although developing
      cartilages were well-organized and had bmp-4 expressing perichondrocytes, the
      spike cartilage did not have such a structure, but only showed sparse bmp-4
      expression. Application of BMP4-soaked beads to the spike led to the induction of
      a joint-like structure. These results suggest that the lack of joints in the
      spike is due to the deficiency of the accumulation of the cells that express bmp
      4. Improvement of regeneration in the Xenopus adult limb that we report here for
      the first time will give us important insights into epimorphic regeneration.

PMID- 15977183
TI  - Cre-mediated site-specific recombination in zebrafish embryos.
AB  - Cre-mediated site-specific recombination has become an invaluable tool for
      manipulation of the murine genome. The ability to conditionally activate gene
      expression or to generate chromosomal alterations with this same tool would
      greatly enhance zebrafish genetics. This study demonstrates that the HSP70
      promoter can be used to inducibly control expression of an enhanced green
      fluorescent protein (EGFP) -Cre fusion protein. The EGFP-Cre fusion protein is
      capable of promoting recombination between lox sites in injected plasmids or in
      stably inherited transgenes as early as 2 hr post-heat shock induction. Finally,
      the levels of Cre expression achieved in a transgenic fish line carrying the
      HSP70-EGFP-cre transgene are compatible with viability and both male and female
      transgenic fish are fertile subsequent to induction of EGFP-Cre expression.
      Hence, our data suggests that Cre-mediated recombination is a viable means of
      manipulating gene expression in zebrafish.

PMID- 15977184
TI  - Toxicology of AHS important chemicals.

PMID- 15977185
TI  - Glutathione S-transferases as putative host susceptibility genes for cancer risk
      in agricultural workers.

PMID- 15977186
TI  - Discussion and conclusions.

PMID- 15977188
TI  - Effect of silybin and its glycosides on the expression of cytochromes P450 1A2
      and 3A4 in primary cultures of human hepatocytes.
AB  - Four beta-glycosides of flavonoligan silybin, i.e. silybin beta-galactoside,
      silybin beta-glucoside, silybin beta-maltoside, silybin beta-lactoside were
      synthesized in order to improve silybin water solubility and bioavailability
      (Kren et al., J Chem Soc, Perkin Trans 1, 2467-2474, 1997). The presented paper
      deals with the effect of silybin and its synthetic beta-glycosides on the
      expression of two major cytochrome P450 isoforms, CYP1A2 and CYP3A4. Primary
      cultures of human hepatocytes were the model of choice. mRNAs were analyzed using
      Northern blot and P-radiolabelled probes. CYP protein content was determined by
      immunoblotting using specific antibodies. Silybin and its beta-glycosides do not
      induce expression of CYP1A2 and CYP3A4. Tested compounds did not affect inducible
      expression of CYP1A2 and CYP3A4 by dioxin and rifampicin, respectively, as
      evaluated at the level of mRNAs and proteins. Silybin and its beta-glycosides do
      not interfere with the expression of CYP1A2 and CYP3A4, are not likely to produce
      drug-drug interactions in terms of the inducibility of two important cytochromes
      P450.

PMID- 15977189
TI  - A study on immunological responses to exposures encountered in corn farming.

PMID- 15977190
TI  - Biomarkers of thyroid function, genotoxicity and agricultural fungicide use.

PMID- 15977191
TI  - Biomarkers of effects: the immune system.

PMID- 15977192
TI  - Paraoxonase 1 (PON1) status and risk of insecticide exposure.

PMID- 15977193
TI  - Role of host susceptibility to toxicity and cancer caused by pesticides:
      cytochromes P450.

PMID- 15977194
TI  - DNA replication and repair reactions relevant to the AHS.

PMID- 15977195
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leptin on hypothalamic
      mRNA expression of factors participating in food intake regulation in a TCDD
      sensitive and a TCDD-resistant rat strain.
AB  - An acutely toxic dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to a
      drastically and permanently reduced feed intake and wasting by an unknown
      mechanism. We focused on the possible interference of TCDD with hypothalamic
      factors known to take part in the regulation of eating and metabolism, utilizing
      the over 1000-fold TCDD-sensitivity difference between Long-Evans (Turku/AB; L-E)
      and Han/Wistar (Kuopio) rats. The mRNA expression of 18 hypothalamic factors
      (including NPY, AgRP, and CART) was measured by quantitative RT-PCR at 6, 24 and
      96 h after TCDD administration. The effects of TCDD were compared with those of
      leptin and with feed restriction employing a TCDD dose that elicited a severe
      reduction of feed intake in L-E rats. TCDD mainly modified expression of
      orexigenic factors causing an initial suppression followed by reversal to
      enhanced expression by 96 h. The latter was also seen in feed-restricted
      controls. In contrast, leptin altered both orexigenic and anorexigenic factor
      mRNAs in a more even manner and its effects were clustered at 6 h. The transient
      nature of feeding-promoting factor suppression does not strongly support a key
      role for this phenomenon in TCDD-induced wasting syndrome. However, the fact that
      TCDD mainly affected orexigenic factors and the temporal differences in response
      found between the rat strains warrant further research.

PMID- 15977196
TI  - Endogenous antioxidant defence system in rat liver following mercury chloride
      oral intoxication.
AB  - Mercury is a highly toxic metal which induces oxidative stress. Superoxide
      dismutases, catalase, and glutathion peroxidase are proteins involved in the
      endogenous antioxidant defence system. In the present study rats were
      administered orally, by gavage, a single daily dose of HgCl2 for three
      consecutive days. In order to find a relation between the proteins involved in
      the antioxidant defence and mercury intoxication, parameters of liver injury,
      redox state of the cells, as well as intracellular protein levels and enzyme
      activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent
      superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were
      assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg
      produced liver damage which that was detected by a slight increase in serum
      alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio
      was assayed as a parameter of oxidative stress and a significant decrease was
      detected, as well as significant increases in enzyme activities and protein
      levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD
      were parallel to those of liver injury and oxidative stress, while the changes
      detected in catalase and GPx activities were progressively increased along with
      the mercury intoxication. Other enzyme activities related to the glutathione
      redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate
      dehydrogenase (G6PDH), also increased progressively. We conclude that against low
      doses of mercury that produce a slight oxidative stress and liver injury, the
      response of the liver was to induce the synthesis and activity of the enzymes
      involved in the endogenous antioxidant system. The activities of all the enzymes
      assayed showed a rapidly induced coordinated response.

PMID- 15977197
TI  - Effect of subchronic acrylamide exposure on the expression of neuronal and
      inducible nitric oxide synthase in rat brain.
AB  - Acrylamide (ACR) is a known industrial neurotoxic chemical. Evidence suggests
      that ACR neurotoxic effect is related to brain neurotransmission disturbances.
      Since nitric oxide (NO) acts as a neurotransmission modulator and is produced by
      nitric oxide synthase (NOS), the neuronal NOS (nNOS) and inducible NOS (iNOS)
      expression pattern were determined in rat cerebral cortex and striatum after
      subchronic exposure to ACR. Using immunocytochemistry, the neuronal count of nNOS
      or optical density of iNOS from sections at three coronal levels, bregma 1.0, 
      0.4, and -2.3 mm, were compared between ACR-treated and control rats. At all
      three levels, nNOS expressions were uniformly decreased in most of the
      neocortical subregions following the treatment of ACR. At bregma level 1.0 mm,
      total numbers of nNOS expressing neurons were significantly decreased to 58.7%
      and 64.7% of the control in the cortex and striatum of ACR-treated rats,
      respectively. However, at the bregma level -2.3 mm, ACR treatment did not produce
      a significant difference in the numbers of nNOS expressing neurons both in the
      cortex and striatum. Contrary to nNOS, iNOS expressions were consistently
      increased to approximately 32% in the neocortex and 25% in the striatum,
      following the subchronic ACR treatment. These data suggest that subchronic ACR
      exposure involves compensatory mechanism on nNOS and iNOS expression to maintain
      the homeostasis of NO at the rostral part of the neocortex and the striatum.
      However, in the caudal brain, increased iNOS expression did not suppress nNOS
      expression. Therefore, the present study is consistent with the hypothesis that
      ACR toxicity is mediated through the disturbance to the NO signaling pathway and
      exhibits a rostrocaudal difference through the differential expressions of nNOS
      and iNOS in the neocortex and the striatum.

PMID- 15977198
TI  - The Agricultural Health Study biomarker workshop on cancer etiology.
      Introduction: overview of study design, results, and goals of workshop.

PMID- 15977199
TI  - Generation of reactive intermediates.

PMID- 15977200
TI  - Identification of biomarkers of arsenic exposure and metabolism in urine using
      SELDI technology.

PMID- 15977202
TI  - Circulatory function and hepatorenal syndrome in cirrhosis.
AB  - The pathogenic mechanism of hepatorenal syndrome is not well established. We
      investigated the circulatory function in cirrhosis before and after the
      development of hepatorenal syndrome. Systemic and hepatic hemodynamics and the
      activity of endogenous vasoactive systems were measured in 66 patients who had
      cirrhosis with tense ascites and normal serum creatinine levels; measurements
      were repeated at follow-up in 27 cases in whom hepatorenal syndrome had
      developed. At baseline, mean arterial pressure and cardiac output were
      significantly higher, and hepatic venous pressure gradient, plasma renin
      activity, and norepinephrine concentration were significantly lower in patients
      who did not develop hepatorenal syndrome compared with those presenting with this
      complication. Peripheral vascular resistance was decreased to the same extent in
      the two groups. Plasma renin activity and cardiac output were the only
      independent predictors of hepatorenal syndrome. Hepatorenal syndrome occurred in
      the setting of a significant reduction in mean arterial pressure (83 +/- 9 to 75
      +/- 7 mmHg; P < .001), cardiac output (6.0 +/- 1.2 to 5.4 +/- 1.5 L/min; P <
      .01), and wedged pulmonary pressure (9.2 +/- 2.6 to 7.5 +/- 2.6 mmHg; P < .001)
      and an increase in plasma renin activity (9.9 +/- 5.2 to 17.5 +/- 11.4 ng/mL .
      hr; P < .001), norepinephrine concentration (571 +/- 241 to 965 +/- 502 pg/mL; P
      < .001), and hepatic venous pressure gradient. No changes were observed in
      peripheral vascular resistance. In conclusion, these data indicate that
      hepatorenal syndrome is the result of a decrease in cardiac output in the setting
      of a severe arterial vasodilation.

PMID- 15977203
TI  - Role of development in the evolution of the scapula of the giant sthenurine
      kangaroos (Macropodidae: Sthenurinae).
AB  - Extinct giant sthenurine kangaroos possessed scapulae morphologically distinct
      from those of all other extant and extinct adult macropodids, but qualitatively
      resembling those of newborn macropodids. The similarity between adult sthenurine
      and neonatal macropodid scapulae suggests that a developmental process, such as
      heterochrony, might have been behind the evolution of the unique sthenurine
      scapular morphology. By incorporating adult and ontogenetic data, this study
      examines the evolution and development of the sthenurine scapula. This study
      quantitatively upholds the previous qualitative morphological observations of
      macropodid scapulae and finds that ontogenetic and evolutionary morphological
      changes are correlated in macropodids. The similarity of scapula morphology in
      sthenurines and newborn macropodids, the correlation between ontogenetic and
      evolutionary morphological change, and information from other sources (i.e.,
      sthenurine evolutionary history) suggests that pedomorphic shifts in morphology,
      most likely due to neotenic processes, occurred within the development of the
      scapula of giant sthenurines.

PMID- 15977204
TI  - Vibration-induced disruption of retrograde axoplasmic transport in peripheral
      nerve.
AB  - Hand-arm vibration syndrome (HAVS) results from excessive exposure to hand
      transmitted vibration. Whether the peripheral nerve damage characteristic of HAVS
      is a direct result of vibration or is secondary to vascular insufficiency remains
      unclear. The purpose of this study was to explore the effect of vibration
      exposure on axoplasmic transport in peripheral nerves and soleus motor neurons.
      Sciatic nerves and motor neurons from rats following two 5-h periods of vibration
      exposure demonstrated disruption in retrograde transport compared to normal.
      After 10 days of vibration (5 h/day), axoplasmic transport failed to recover
      within 24-48 h in most rats. This study demonstrates that disrupted axoplasmic
      transport is an early consequence of short-term vibration exposure. The effects
      of vibration on axoplasmic transport also appear to be cumulative. This study
      provides a new biological way to evaluate measures to prevent early vibration
      injury.

PMID- 15977205
TI  - Morbid obesity, nonalcoholic fatty liver disease, and weight loss surgery.
AB  - OBJECTIVE: This study examines the impact of biliopancreatic diversion, a
      malabsorptive variant of gastric bypass, on liver histology. METHODS: Liver
      samples were collected from 689 severely obese (BMI 47 +/- 9 kg m(2)) patients
      undergoing biliopancreatic diversion. Exclusion criteria included: history of
      hepatitis, exposure to hepatotoxic medications, prior weight loss surgery, and
      alcohol consumption greater than 100 grams per week. One group of 14 patients had
      cirrhosis in their initial biopsy. Eleven of those 14 patients underwent multiple
      biopsies to monitor their liver disease. A second group of 104 patients had re
      operations and a second liver biopsy. A hepatopathologist conducted blind
      evaluations of all biopsy specimens looking for steatosis and fibrosis. RESULTS:
      All patients lost weight and showed improvement in their metabolic syndrome. Of
      the 104 patients undergoing re-operation with a second liver biopsy, 28 showed a
      decrease in severe fibrosis, while 42 patients developed mild fibrosis. On
      average, this group lost 38 +/- 18 kg over 41 +/- 25 post-surgical months. A sub
      group analysis revealed an association between increased fibrosis and post
      operative low serum albumin, diarrhea, pre-operative alcohol consumption, and
      menopausal status. The eleven patients with cirrhosis in their initial biopsy
      showed a reduction in their fibrosis grade (mean fibrosis grade from 5 to 3)
      during nine years of follow-up care. CONCLUSION: These findings indicate that
      significant weight loss after biliopancreatic diversion can improve liver
      histology in patients with advanced fibrosis.

PMID- 15977211
TI  - Inefficacy of F-18 fluorodeoxy-D-glucose-positron emission tomography scans for
      initial evaluation in early-stage cutaneous melanoma.
AB  - BACKGROUND: The purpose of the current study was to determine the sensitivity and
      specificity of initial F-18 fluorodeoxy-D-glucose-positron emission tomography
      (FDG-PET) scanning for detection of occult lymph node and distant metastases in
      patients with early-stage cutaneous melanoma. METHODS: The authors conducted a
      prospective nonrandomized clinical trial. Inclusion criteria were patients with
      cutaneous melanoma tumors > 1.0 mm Breslow thickness, local disease recurrence,
      or solitary intransit metastases without regional lymph or distant metastases by
      standard clinical evaluation. All patients underwent whole-body FDG-PET scanning
      before surgical therapy. Abnormal PET findings were studied by targeted
      conventional imaging and/or biopsy. FDG-PET scans were interpreted in a blinded
      fashion. Regional lymph node basins were staged by sentinel lymph node biopsy
      (SLNB). PET scan findings in regional lymph nodes were compared with histology of
      SLNB specimens. Abnormal distant PET scan findings were studied with repeat
      conventional scan imaging at 3-6 months and were correlated with the first
      site(s) of clinical disease recurrence. Blinded PET scan findings were correlated
      with all information to determine sensitivity and specificity. RESULTS: There
      were 144 assessable patients with a mean tumor depth of 2.8 mm. The median follow
      up for these patients was 41.4 months. Blinded interpretations of FDG-PET scan
      images showed that 31 patients (21%) had signs of metastatic disease, 13 patients
      had probable regional lymph node metastases, and 18 patients had 23 sites of
      possible distant metastases. SLNB and/or follow-up demonstrated regional lymph
      node metastases in 43 of 184 lymph node basins in 40 patients (27.8%). Compared
      with all clinical information, FDG-PET scan sensitivity for detection of regional
      lymph node metastases was 0.21 (95% confidence [CI], 0.10-0.36) and specificity
      was 0.97 (95% CI, 0.93-0.99). No distant sites were confirmed to be true positive
      by targeted conventional imaging/biopsy at the time of presentation. Thirty-four
      patients (23.6%) presented with 54 foci of metastatic disease at initial disease
      recurrence. FDG-PET scan sensitivity for prediction of the first site(s) of
      clinical disease recurrence was 0.11 (95% CI, 0.04-0.23). Excluding patients with
      brain metastases, FDG-PET scan sensitivity for detection of occult Stage IV
      disease in patients was 0.04 (95% CI, 0.001-0.20) and specificity was 0.86 (95%
      CI, 0.79-0.92). CONCLUSIONS: FDG-PET scanning did not impact the care of patients
      with early-stage melanoma already staged by standard techniques. Routine FDG-PET
      scanning was not recommended for the initial staging evaluation in this
      population.

PMID- 15977212
TI  - 2-Chlorodeoxyadenosine and cytarabine combination therapy for idiopathic
      hypereosinophilic syndrome.
AB  - BACKGROUND: Hypereosinophilic syndrome (HES) is a rare, disabling, and incurable
      disease. In this study, a combination of 2-chlorodeoxyadenosine (2-CdA) and
      cytosine arabinoside (ara-C) chemotherapy was evaluated in patients with HES.
      METHODS: Nine patients with HES were treated with ara-C (1 g/m(2)) given
      intravenously over 2 hours at 0 hours, 48 hours, 72 hours, 96 hours, and 120
      hours; and 2-CdA (12 mg/m(2) per day) was given as a continuous intravenous
      infusion over 5 days starting at 24 hours. A second course of the same therapy
      was administered in patients who had a response. RESULTS: All patients had signs
      and symptoms of end-organ involvement. The median time from diagnosis to therapy
      was 25 months. Seven patients had received prior therapies. Five patients (55%)
      achieved a complete remission (CR), 1 after receiving 2 courses of therapy.
      Elimination of eosinophilia was accompanied by the resolution of symptoms. The
      median disease-free survival and overall survival after the diagnosis for
      patients who achieved CR was 26 months and 44 months, respectively. Treatment was
      tolerated well. Febrile neutropenia occurred in 28% of the 14 courses that were
      given. The median time to recovery from neutropenia and thrombocytopenia was 17
      days and 39 days, respectively. CONCLUSIONS: The combined 2-CdA and ara-C
      chemotherapy regimen had activity in patients with HES.

PMID- 15977213
TI  - Successful carboplatin desensitization in patients with proven carboplatin
      allergy.
AB  - BACKGROUND: Carboplatin is one of the most useful and well tolerated cytotoxic
      drugs for gynecologic malignancies. Hypersensitivity to carboplatin is not rare
      among patients receiving multiple recurrent treatments with this drug. The aim of
      the current study was to offer a safe and convenient carboplatin desensitization
      strategy to patients with a proven allergic reaction to this drug. METHODS:
      Patients with an immediate objective allergic reaction to carboplatin were skin
      tested with the drug. A 6-hour carboplatin desensitization protocol was
      administered to the patients with a carboplatin-positive skin test on each of the
      following treatment courses. RESULTS: Twenty-three patients with an allergic
      reaction to carboplatin and a positive skin test were included in the current
      study. Twenty patients (86.9%) were desensitized. One patient developed a mild
      urticarial rash. Nineteen patients tolerated 80 desensitization courses
      uneventfully. CONCLUSIONS: The data presented a successful desensitization
      protocol for individuals with a proven allergic reaction to carboplatin. The
      protocol was safe and convenient and offered an effective therapeutic strategy to
      patients who required this drug.

PMID- 15977218
TI  - Improving the reproducibility of diagnosing micrometastases and isolated tumor
      cells.

PMID- 15977220
TI  - Brain morphology in nonsyndromic unicoronal craniosynostosis.
AB  - Studies of isolated craniosynostosis have shown biomechanical and biochemical
      influences on the craniofacial phenotype, resulting from both genetic and
      epigenetic factors. Much less attention has been directed toward the morphology
      of the brain, despite the interactive nature of the developing skull and
      developing brain. The aim of this study is to define the morphology of the brain
      in nonsyndromic unilateral coronal synostosis (UCS) in order to form more
      complete hypotheses about the cause of craniosynostosis. Landmark coordinate data
      were collected from 3D magnetic resonance image reconstructions of the brain in a
      sample of UCS patients and an age-matched morphologically normal cohort. These
      data were analyzed using Euclidean distance matrix analysis. The results of our
      study demonstrate that despite the basic similarity of overall shape of the brain
      and skull in UCS, the effects of craniosynostosis on the brain are not localized
      to structures immediately adjacent to the fused suture or to the endocranial
      surface of the skull. Rather, alterations are observed throughout the volume of
      the brain, with subcortical structures altered in conjunction with cortical
      changes. These results indicate that the morphological correlates are different
      for brain and skull and suggest that there is a large degree of independence in
      the developmental trajectories of the brain and skull.

PMID- 15977221
TI  - Internal luminal pressure during early chick embryonic brain growth: descriptive
      and empirical observations.
AB  - If the intraluminal pressure of the brain is decreased for 24 hr, the brain and
      neuroepithelium volumes are both reduced in half. The current study measured the
      intraluminal pressure throughout the period of rapid brain growth using a servo
      null micropressure monitoring system. From 613 measurements made on 55 embryos,
      we show that the intraluminal pressure over this time period is appropriately
      described by a linear model with correlation coefficient of 0.752. To assess
      whether sustained hyperpressure would increase mitosis, elevated intraluminal
      pressure was induced in 10 embryos for 1-hr duration via a gravity-fed drip. The
      mitotic density and index of the mesencephalon were measured for the 10 embryos.
      Those embryos, in which the colchicine solution was added to the intraluminal
      cerebrospinal fluid creating a sustained hyperpressure, exhibited at least a 2.5
      fold increase in both the mitotic density and index compared with control
      embryos. Based on the small sample size, we cautiously conclude that sustained
      hyper-intraluminal pressure does stimulate mitosis.

PMID- 15977222
TI  - Normal distribution of melanocytes in the mouse heart.
AB  - We report the consistent distribution of a population of pigmented trp-1-positive
      cells in several important septal and valvular structures of the normal mouse
      (C57BL/6) heart. The pigmented cell population was first apparent by E16.5 p.c.
      in the right atrial wall and extended into the atrium along the interatrial
      septum. By E17.5, these cells were found along the apical membranous
      interventricular septum near or below the surface of the endocardium. The most
      striking distribution of dark pigmented cells was found in the tricuspid and
      mitral valvular leaflets and chordae tendineae. The normal distribution of
      pigmented cells in the valvuloseptal apparatus of C57BL/6 adult heart suggests
      that a premelanocytic lineage may participate in the earlier morphogenesis of the
      valve leaflets and chordae tendineae. The origin of the premelanocyte lineage is
      currently unknown. The most likely candidate populations include the neural crest
      and the epicardially derived cells. The only cell type in the heart previously
      shown to form melanocytes is the neural crest. The presence of neural crest
      cells, but not melanocytes, in some of the regions we describe has been reported
      by others. However, previous reports have not shown a contribution of melanocytes
      or neural crest derivatives to the atrioventricular valve leaflets or chordae
      tendineae in mouse hearts. If these cells are of neural crest origin, it would
      suggest a possibly greater contribution and persistence of neural crest cells to
      the valvuloseptal apparatus than has been previously understood.

PMID- 15977223
TI  - Regional cardiac ganglia projections in the guinea pig heart studied by
      postmortem DiI tracing.
AB  - Our purpose was to identify and localize intrinsic cardiac ganglia innervating
      distinct regions of the heart using postmortem tracing of nerve projections with
      DiI, a method not previously used to study the intrinsic cardiac nervous system.
      We also investigated the possibility of collateral innervation of myocardium and
      intrinsic ganglia. In isolated paraformaldehyde-fixed guinea pig hearts, crystals
      of DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) were
      inserted into the posterior ventricular myocardium below the atrioventricular
      groove, the right atrium, or the left ventricular septum. Hearts were placed in
      the dark at 37 degrees C for 2-14 weeks to allow DiI diffusion within neuronal
      membranes. Labeled neurons were observed in intracardiac ganglia after at least 4
      weeks of dye exposure. Labeling was restricted to the inferior-most ganglia
      (those near the atrioventricular groove) when DiI was inserted into the posterior
      ventricular myocardium and to ganglia near the sinus node after right atrial DiI
      placement. Application of DiI to the left ventricular septum resulted in neuron
      labeling in ganglia primarily in the interatrial septum near the atrioventricular
      node. After 8 weeks, DiI-labeled nerve fibers and varicosities were seen
      surrounding unlabeled neurons in some ganglia, suggesting that axons terminating
      in or passing through the DiI application site in posterior ventricular tissue
      had collateral branches innervating these ganglia. These results indicate that
      intrinsic innervation of major cardiac subdivisions is accomplished by regionally
      segregated cardiac ganglia. Also, tracing with DiI has provided evidence for
      collateral nerve projections that could be the substrate for novel intracardiac
      regulatory circuits.

PMID- 15977224
TI  - Serum IgA levels induced by rotavirus natural infection, but not following
      immunization with the RRV-TV vaccine (Rotashield), correlate with protection.
AB  - To directly compare serum rotavirus specific IgA as a marker of protection in
      children vaccinated with the RRV-TV (Rotashield) vaccine and in naturally
      infected children, we studied pre-existing rotavirus IgA antibodies by ELISA
      assays in these groups of children within the first 5 days after the onset of a
      diarrhea episode, due or not to rotavirus. In immunized children, rotavirus IgA
      titers were similar between infected and non-RV infected children. In non
      immunized children, the proportion with rotavirus IgA titers was significantly
      greater in non-RV infected children (58%) than in infected children (31%).
      Additionally, a titer >/=1:800 was associated with 68% protection. Thus, in this
      study serum rotavirus IgA showed a good correlation with protection in children
      pre-exposed to natural infection but not in those immunized with the RRV-TV
      vaccine.

PMID- 15977225
TI  - Surveillance of acute hepatitis C in Cairo, Egypt.
AB  - Surveillance of acute hepatitis has been set up in two fever hospitals in Cairo
      to diagnose acute hepatitis C. Patients were categorized as definite acute
      hepatitis C with positive hepatitis C virus (HCV) RNA and without anti-HCV
      antibody, or probable acute hepatitis C with positive HCV RNA, positive anti-HCV
      antibody, alanine aminotransferase >/=4 times the upper limit of normal (ULN),
      and high risk parenteral exposure in the 1--3 months prior to the beginning of
      symptoms. From May to November 2002, 315 patients were recruited in the study. Of
      these, 115 (36.5%) had acute hepatitis A, 89 (28.3%) had acute hepatitis B, and
      111 (35.2%) had non-A non-B acute hepatitis. Of the total with complete data
      (n=309), 12 (3.9%, 95% CI=2.0%-6.7%) had definite acute hepatitis C, and 11
      (3.6%, 95% CI=1.8%-6.3%) had probable acute hepatitis C. In patients with
      definite acute hepatitis C, dental exposure (n=5) and intravenous drug use (n=2),
      were the only high risk procedures found in the 6 months prior to diagnosis. Five
      patients had no identifiable parenteral exposure. In conclusion, results from
      this study suggest that acute hepatitis C can be diagnosed by surveillance of
      acute hepatitis in hospital settings in Cairo and that minor community exposures
      contribute substantially to local HCV transmission.

PMID- 15977226
TI  - Detection and genotyping of GBV-C virus in the United Arab Emirates.
AB  - GB virus-C/Hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, is spread
      widely and has been reported to be associated with non A-E hepatitis. The aim of
      the current project was to determine the rate of infection and genotypic
      characteristics of GBV-C in the United Arab Emirates (UAE). A total of 379
      plasma/serum samples representing different populations in the UAE and comprising
      healthy as well as patients positive for HBV and HCV were screened using RT
      PCR/nested PCR of the 5'-untranslated region (UTR). National subjects (n=168) and
      non-nationals residing in the UAE (n=211) were tested. The results obtained
      showed that the rate of GBV-C infection in healthy nationals, and those positive
      for HCV or HBV were 11.1%, 14.3%, and 5.7%, respectively, compared to 8.3%,
      33.3%, and 8.6%, respectively, in non-nationals. No statistically significant
      correlation between infection with GBV-C and HCV or HBV (P>0.05) was found.
      Sequence analysis of the 5'-UTR using 37 and 46 clones from 8 and 6 healthy
      nationals and non-nationals, respectively, revealed the prevalence of the
      European/North American genotype 2 when compared to the five reference genotypes
      in GenBank.

PMID- 15977227
TI  - Cytomegalovirus and human herpesvirus 8 DNA detection in peripheral blood
      monocytic cells of AIDS patients: correlations with the presence of Kaposi's
      sarcoma and CMV disease.
AB  - To establish the effect of the presence in blood cells of cytomegalovirus (CMV)
      and human herpesvirus 8 (HHV8) DNA, two herpesviruses that are activated
      frequently in AIDS patients, were selected from the Amsterdam Cohort Studies on
      HIV/AIDS 181 PBMC samples from patients with and without Kaposi's sarcoma (KS),
      and with and without CMV-related disease. The viral loads of both HHV8 and CMV
      were determined by real-time PCR at the time of diagnosis of AIDS. There was no
      significant difference in prevalence and load for CMV between the KS and non-KS
      patients. The variable related most strongly to KS was the presence of HHV8 DNA
      in PBMCs, whilst CMV DNA was related to the development of CMV disease and
      shortened survival. The frequency of detection of HHV8 increased when the patient
      presented with more severe KS symptoms at diagnosis, but detection of HHV8 DNA
      did not influence survival. Therefore, HHV8 and CMV DNA measured in the blood of
      AIDS patients, are each related mainly to the associated disease, and have no
      additional predictive value in these patients.

PMID- 15977228
TI  - Hantaviruses in Central South America: phylogenetic analysis of the S segment
      from HPS cases in Parana, Brazil.
AB  - We sequenced the complete S segments of hantaviruses detected from 12 HPS
      patients living in southern of Brazil. Samples were obtained from patients
      diagnosed in different years, in distinct areas, and with a broad spectrum of
      clinical signs. Despite these differences, all the S proteins of hantavirus from
      Parana were identical, except for one amino acid substitution. Phylogenetic
      analyses of the complete S segment nucleotide and amino acid sequences indicated
      that hantaviruses from Parana form a distinct clade from those circulating in
      South and North America. Other hantaviruses from Brazil were not placed in the
      same clade. The Oligoryzomys nigripes-associated strains ITA37 and ITA38 from
      Paraguay were found to belong to the same clade as the hantaviruses from Parana.
      Paraguay and Parana state are located at the same latitude and some ecosystems
      are similar in both places. The geographic position and common rodent hosts could
      explain this phylogenetic relationship.

PMID- 15977229
TI  - Human herpesvirus type 8 infection in an area of Northern Italy with high
      incidence of classical Kaposi's sarcoma.
AB  - Previous studies have reported a large variation in the incidence of classical
      Kaposi's sarcoma across different Districts of the province of Mantua (Northern
      Italy). To assess whether such differences might be explained by different anti
      HHV8 antibody prevalence, a serological study was conducted in 343 healthy
      elderly individuals resident in two adjacent Districts, at the highest and the
      lowest classical Kaposi's sarcoma incidence rate, respectively. Qualitative and
      quantitative determinations of IgG antibodies against both latent and lytic HHV-8
      antigens were performed by indirect immunofluorescence assay. The assay's
      sensitivity was studied in 26 patients with classical Kaposi's sarcoma. Overall,
      anti-HHV8 antibodies were detected in 25 out of 26 patients (96%), confirming the
      high sensitivity of this assay. The prevalence of anti-HHV-8 antibodies was
      higher among individuals living in the District had a high incidence of classical
      Kaposi's sarcoma compared to those living in the District with low incidence
      (19.4% vs 9.8%, and 15.9% vs 8%; P<0.05, for latent and lytic antibodies,
      respectively). Anti-lytic antibody GMT was higher in people living in the
      District at high incidence rate compared to those of the other area (328.9 vs.
      180.4; P<0.01). A higher prevalence of HHV-8 infection was found among persons
      living in municipalities surrounded by watercourses (OR 2.2, 95% CI: 1.10-4.32).
      In conclusion, variation in HHV-8 prevalence appears to explain differences in
      the incidence rates of classical Kaposi's sarcoma observed in different areas of
      the province.

PMID- 15977230
TI  - Fitness of Japanese encephalitis virus to Neuro-2a cells is determined by
      interactions of the viral envelope protein with highly sulfated
      glycosaminoglycans on the cell surface.
AB  - Genetically different subpopulations were identified and purified from Japanese
      Encephalitis virus (JEV). Those with small plaques (SPs; <2 mm in diameter),
      derived from strains of T1P1, CJN, and CC27, were more competent than those with
      large plaques (LPs; >5 mm in diameter) when passaged in Neuro-2a cells.
      Differences in amino acids between SPs and LPs from each strain were shown in the
      viral envelope (E) protein. The amino acid at E-306 was Glu in LP but was
      substituted by Lys in SP in the T1P1 strain. A similar substitution occurred at E
      138 in the CJN strain. However, the amino acid was Asp in LP but was substituted
      by Asn in SP at E-389 in the CC27 strain. All SPs were shown to have a higher
      affinity to the cellular membrane when compared to LPs, and this resulted in more
      efficient infection of Neuro-2a cells, suggesting that the differential fitness
      of JEV variants to Neuro-2a cells appeared in the early phase of infection. In
      addition, glycosaminoglycans (GAGs) on the surface of many mammalian cells have
      been demonstrated to be critical for infection by JEV, especially SP variants.
      The present results suggest that T1P1-SP1 viruses infected Neuro-2a cells more
      efficiently in spite of the sparse distribution of cell surface GAGs. We conclude
      that highly sulfated forms of GAGs expressed by Neuro-2a cells play an important
      role in selecting JEV variants with specific mutations in the E glycoprotein.

PMID- 15977231
TI  - Norovirus contamination found in oysters worldwide.
AB  - Noroviruses (Norwalk-like viruses) are recognized as major causes of acute
      gastroenteritis worldwide. Outbreaks of norovirus gastroenteritis are often
      associated with consumption of oysters. In this study, oysters imported into Hong
      Kong from 11 countries over a 3-year period were screened by RT-PCR. Overall, 53
      out of 507 (10.5%) samples were positive for norovirus-RNA, and a wide variety of
      strains were found. Two novel genetic clusters were detected, which could
      indicate novel human or animal norovirus strains. However, whether these two new
      clusters are of human or animal origin is not known. Thirteen outbreaks, in which
      oysters were implicated as the source of infection were investigated: Norovirus
      RNA sequences could be detected in oysters from six outbreaks, but only in one
      outbreak the strains isolated from patients and oysters matched (>98% homology).
      Therefore, RT-PCR was of use in detecting norovirus contamination of oysters
      implicated in an outbreak, but was less useful in demonstrating an actual
      molecular epidemiological link with human cases. It was shown that contamination
      by noroviruses could be demonstrated in oysters worldwide, and therefore oysters
      may serve as an important vehicle for introducing novel norovirus strains.

PMID- 15977232
TI  - Hepatitis C virus-core and non structural proteins lead to different effects on
      cellular antioxidant defenses.
AB  - Chronic hepatitis C virus (HCV) infection leads to increased oxidative stress in
      the liver. Hepatic antioxidant enzymes provide an important line of defense
      against oxidative injury. To understand the antioxidant responses of hepatocytes
      to different HCV proteins, we compared changes in antioxidative enzymes in HCV
      core and HCV-nonstructural protein expressing hepatocyte cell lines. We found
      that expression of HCV-core protein in hepatocyte cell lines leads to increased
      oxidative stress as determined by increased in the oxidant-sensitive probe 5-(and
      6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-DCFH(2))
      fluorescence, decreased reduced glutathione (GSH), and increased oxidation of
      thioredoxin (Trx). Although the expression of HCV-nonstructural (HCV-NS) proteins
      led to increased oxidative stress as well, the antioxidant enzymatic responses
      were different. Over-expression of HCV-NS proteins increased antioxidant enzymes
      (MnSOD and catalase), heme oxygenase-1 (HO-1), and GSH, indicating different
      mechanism(s) of prooxidative activity than HCV-core protein. Our findings show
      that different HCV proteins induce different antioxidant defense responses in
      hepatocytes. These findings may facilitate understanding the interaction of
      different HCV proteins with infected liver cells and help identify possible
      factors contributing to hepatocyte damage during HCV infection.

PMID- 15977233
TI  - Serological and molecular studies on subclinical hepatitis E virus infection
      using periodic serum samples obtained from healthy individuals.
AB  - Subclinical hepatitis E virus (HEV) infection among healthy individuals was
      studied serologically and molecularly. Serum samples collected at screening
      between March and April 2004 (or just before retirement) from 266 medical staff
      members (35 males, 231 females) who had been working for 8.8 +/- 8.5 (mean +/-
      standard deviation, range, 0.3-35.1) years in a city hospital in Japan and serum
      samples that had been collected from these staff members at the start of
      employment were tested for IgA, IgM, and IgG antibodies to HEV (anti-HEV) by in
      house enzyme-linked immunosorbent assays. Overall, six subjects (2.3%) tested
      positive for anti-HEV IgG at the screening; among them, four subjects (1.5%) had
      already been positive for anti-HEV IgG at the start of employment and two
      subjects (0.8%) seroconverted after initiation of employment. Periodic serum
      samples that had been collected from the two seroconverted subjects were tested
      for HEV antibodies and HEV RNA. The two subjects became positive for anti-HEV IgG
      in 1978 or 2003, respectively, with no discernible elevation in alanine
      aminotransferase (ALT) level, and continued to be seropositive up through the
      screening date. Although anti-HEV IgM was not detectable in the two subjects, one
      was infected transiently with Japan-indigenous HEV strain of genotype 3 and the
      other was positive transiently for anti-HEV IgA. The present study indicates that
      even an individual with subclinical HEV infection had evidence of transient
      viremia in the absence of ALT elevation and that anti-HEV IgA detection may be
      useful for serological diagnosis of recent subclinical HEV infection.

PMID- 15977234
TI  - Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus
      infections.
AB  - C-reactive protein is one of the most widely used indicators of the response of
      acute-phase proteins. The measurement of C-reactive protein in dengue, however,
      is clinically not useful, because of marginally elevated levels and absent
      association with disease severity. The prototypic long pentraxin, pentraxin 3, is
      an acute phase protein that is structurally related but distinct from C-reactive
      protein which has proven to correlate with the severity of bacterial infection in
      critically ill patients. The potential involvement of pentraxin 3 in dengue and
      its aptitude to predict more severe disease or poor clinical outcome has not been
      studied previously. We therefore measured pentraxin 3 plasma levels in 44 dengue
      virus infected patients. Pentraxin 3 levels were strikingly higher when compared
      to C-reactive protein levels, with highest pentraxin 3 values observed in the
      first 7 days after the onset of symptoms. Median pentraxin 3 levels at admission
      and peak levels during follow up were higher in patients suffering from dengue
      shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak
      values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared
      to levels found in patients with dengue fever and dengue hemorrhagic fever (at
      admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values
      during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our
      results indicate that pentraxin 3 seems to be a marker of infection better than C
      reactive protein in dengue. The role of pentraxin 3 in the pathogenesis of dengue
      and its potential as an early prognostic indicator of disease severity needs
      further assessment.

PMID- 15977235
TI  - Evidence of the etiological predominance of norovirus in gastroenteritis
      outbreaks--emerging new-variant and recombinant noroviruses in Hungary.
AB  - Between January 2001 and December 2003, stool specimens from 262 (45%) of 581
      reported outbreaks of gastroenteritis were investigated for noroviruses in
      Hungary. Specimens collected from outbreaks of non-bacterial gastroenteritis were
      examined by reverse-transcription polymerase chain reaction and enzyme
      immunoassay. In 253 (97%) of 262 outbreaks, norovirus was detected and confirmed
      by sequencing in 211 (81%). Hospitals (35%), day care centers (30%), and elderly
      homes (27%) were the most common settings. Diversity and frequency of the
      genotypes changed over time but with predominance (95%) of genogroup (GG) II
      strains. Strains grouped into 11 genotypes including an epidemic spread of new
      variant GGII4 (Lordsdale virus) and a recently emerged group of natural
      recombinant strains (GGIIb/Hilversum polymerase) with four capsid types (Hawaii,
      Mexico, Snow Mountain, and Lordsdale). Clusters of epidemics including food-borne
      outbreaks were detected. According to this study, noroviruses are the predominant
      etiological agents causing gastroenteritis outbreaks in Hungary.

PMID- 15977236
TI  - Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from
      Mozambique before initiation of antiretroviral therapy: results from the DREAM
      programme.
AB  - Phylogenetic analysis and evaluation of drug-resistance were carried out upon 59
      plasma samples from 58 treatment-naive HIV-1 infected patients from Mozambique,
      enrolled in a free antiviral-therapy protocol in the frame of Drug-Resource
      Enhancement against AIDS and Malnutrition (DREAM) programme. Sequencing of the
      first 1,300 bases of the pol-gene shows that all virus strains cluster within
      clade C, with the exception of a single patient carrying a G-subtype virus.
      Relevant mutations in the reverse transcriptase (RT) are rare: 118A/I/L/G (four
      patients), 179E/D/I (three patients), 333E/D (two patients), 101R, and 210F (one
      patient each). In Protease (PR), V82I (10.3%) is the only relevant mutation,
      while natural polymorphisms/secondary mutations are found, some at very high
      frequency: 20R (25.9%), 36I (91.4%), 36L (8.6%), 60E (31.0%), 63P (29.3%), and
      93L (96.6%). Among them, mutations with a frequency >25% were further
      investigated to assess their covariation pattern with PI resistance associated
      mutations. The pattern of covariation observed for K20R and D60E (but not L63P
      and M36I) was different between C and B subtype isolates from PR-inhibitor
      treated patients. The sequences were also analyzed to calculate the ratio of non
      synonymous to synonymous substitution. The ratio for PR and RT was 0.116 and
      0.093, respectively, suggesting a greater conservation in RT than PR in both
      subtypes B and C HIV strains. Taken together, the results demonstrate a
      consistent clade-homogeneity of viral strains circulating in Mozambique, and the
      very limited presence, in drug-naive patients, of mutations associated with
      resistance to RT-inhibitors. The high frequency of secondary
      mutations/polymorphisms in HIV-PR deserves further studies to evaluate its
      relevance in clinical settings.

PMID- 15977237
TI  - Complete genome sequence and phylogenetic analysis of hepatitis B virus isolated
      from Turkish patients with chronic HBV infection.
AB  - Hepatitis viruses are the leading causes of chronic liver disease resulting in
      chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world and also
      in Turkey. Although Turkey has an intermediate rate of hepatitis B virus (HBV)
      infection with a prevalence reported as 5%, a complete HBV genome sequence has
      not been published. In this study, the molecular characterization and
      phylogenetic analysis are described of 11 complete HBV genomes isolated from 11
      naive patients (5 male, 6 female; ages: 18--54 years old, median 35 years old)
      with chronic HBV infection. Of 11 patients, 7 and 4 were HBeAg positive/anti-HBe
      negative and HBeAg negative/anti-HBe positive, respectively. All patients had no
      co-infection with HCV, HDV, or HIV. HBV DNA was extracted from the sera of the
      patients. The complete genome was amplified by PCR and cloned into a TA vector.
      The PCR products were sequenced directly and the complete HBV genome sequences
      were determined. Ten HBV genomes were 3182 base pairs in length. There was a 183
      bp deletion (between nucleotides 2987--3169) in pre-S region in one HBeAg
      positive patient. There were two pre-core stop codons (G1896A) in two HBeAg
      negative and three core promoter dual mutations (T1762/A1764) in one HBeAg
      positive and two HBeAg negative patients' HBV genomes. Phylogenetic analysis of
      all complete genomes yielded that all Turkish sequences were clustered in
      genotype D branch (ten in subgenotype D1 and one in subgenotype D2). The analysis
      of S gene amino acid sequences revealed that surface gene subtypes of one and ten
      HBV strains were subtype ayw3 and ayw2, respectively. This study indicates that
      Turkish patients with chronic hepatitis B infection show very little genotypic
      heterogeneity. Genotype D of HBV DNA and subtype ayw2 of surface gene represent
      almost the whole Turkish patient population infected with HBV.

PMID- 15977238
TI  - Small interfering RNA effectively inhibits protein expression and negative strand
      RNA synthesis from a full-length hepatitis C virus clone.
AB  - Hepatitis C virus (HCV) infection is usually treated with the combination of
      interferon and ribavirin, but only a small fraction of patients develop a
      sustained remission. There is need for the development of specific molecular
      approaches for the treatment of chronic HCV infection. We propose that RNA
      interference is highly effective antiviral strategy that offers great potential
      for the treatment of HCV infection. Three plasmid constructs expressing small
      interfering RNAs (siRNAs) targeted to sequences encoding the structural gene (E2)
      and non-structural genes (NS3, NS5B) of HCV1a genome were prepared. Antiviral
      properties of siRNAs against the HCV1a strain were studied in a transient
      replication model that involved the use of a transcription plasmid containing the
      full-length HCV genome and an adenovirus expressing T7 RNA polymerase. We found
      that siRNAs targeted to the E2, NS3 and NS5B regions of the HCV genome
      efficiently inhibited expression of the HCV core and NS5A protein measured by
      Western blot analysis and immunocytochemical staining. Intracytoplasmic
      immunization of siRNAs in HCV-transfected cells efficiently degraded genomic
      positive strand HCV RNA, as shown by ribonuclease protection assay (RPA). All
      three siRNAs efficiently inhibited synthesis of replicative negative strand HCV
      RNA in the transfected cells. A control siRNA plasmid against a Epstein--Barr
      virus latency gene did not inhibit protein expression and negative strand HCV
      RNA. These results suggest that RNAi is an effective and alternative approach
      that can be used to inhibit HCV expression and replication.

PMID- 15977239
TI  - Unexpected occasional persistence of high levels of HHV-6 DNA in sera: detection
      of variants A and B.
AB  - Previously it was thought that in the immunocompetent human herpesvirus-6 [HHV-6]
      DNA was present transiently in serum during early primary infection but not
      thereafter. In this study, HHV-6 serum IgG avidity was detected by
      immunofluorescence and HHV-6 variants A/B [HHV-6A/B] serum DNA by semi
      quantitative PCR [titre-log(10) copies/ml] in: (a) young children <3 years old
      from an encephalitis Survey, and a control Anonymised Serum Bank and (b)
      children/adults referred for diagnosis. The results showed that 11 out of 15
      children [all <2 years] with primary infection proven by seroconversion had
      transient low levels of serum HHV-6B DNA [mean titre 2.6]. However, 3.3% (6/184)
      of Survey Children had significantly higher levels [mean titre 5.3; 2 HHV-6A; 4
      HHV-6B; P < 0.001]. Similarly high level serum DNA [mean titre 4.0; 4 HHV-6A; 6
      HHV-6B] was found in 1.5% (10/653) of the Serum Bank Children. Moreover, seven
      young children <3 years old [four Survey Children and three referred for
      diagnosis] had high titre serum HHV-6 DNA [mean 4.8] persisting i.e., in all
      available samples [median 186 days]. Three older children >3 years old and 4
      adults [3 of whom were the mothers of 3 of the young children with persisting HHV
      6] also had persisting high titre viral DNA [mean 4.2; median 108 days]. Thus in
      contrast to acute primary infection, where only HHV-6B DNA is found transiently,
      both HHV-6A and B DNA persist in serum at high titre in occasional individuals of
      all ages. The significance of this newly described phenomenon in relation to
      diagnosis, clinical consequences and congenital infection are discussed.

PMID- 15977240
TI  - The impact of high risk human papillomavirus testing in an inner London
      colposcopy clinic.
AB  - This is an audit of a new technique to improve the colposcopy service. Samples
      were tested for high risk HPV DNA using Digene Hybrid Capture II. Sixty-four
      percent of the sampled women under 30 had detectable high risk HPV DNA,
      decreasing to 44% in 30--39 year olds and to 27% in women over 40. High risk HPV
      prevalence increased with severity of cytology, although 22% with normal
      colposcopy had detectable high risk HPV. Of those women treated for cervical
      dysplasia, 83% had detectable high risk HPV prior to treatment, compared to only
      32% afterwards. The audit has shown that high risk HPV testing has considerable
      discriminatory value. It has been integrated successfully into the service,
      particularly to manage low grade cervical abnormalities and to add valuable
      information following treatment for cervical dysplasia. Results need to be
      interpreted alongside colposcopy, cytology, and histology, and care must be taken
      in the interpretation of a single high risk HPV result.

PMID- 15977241
TI  - Prevalence and partial sequence analysis of human T cell lymphotropic virus type
      I in China.
AB  - A total of 145,293 serum samples were collected from volunteer blood donors in 13
      provinces of China and tested for anti-HTLV antibody using an ELISA licensed in
      China. Thirty were positive for anti-HTLV by ELISA and 19 of those 30 samples
      were confirmed positive using a supplemental immunoblot assay. Anti-HTLV-I was
      detected only in samples from Fujian province (a Southern province) where the
      positivity rate was approximately 0.05%. The region encoding gp46 from 5 of the
      19 antibody positive samples was amplified and sequenced. Sequence analysis
      indicated that these isolates belong to HTLV-I genotype A. These data suggest
      that HTLV-I is not endemic throughout China and the virus may be restricted to a
      particular region.

PMID- 15977242
TI  - Diverse pattern of protease inhibitor resistance mutations in HIV-1 infected
      patients failing nelfinavir.
AB  - The aim of the study was to describe the pattern of resistance mutations in human
      immunodeficiency virus type 1 (HIV-1) infected patients experiencing their first
      protease inhibitor (PI) failure on nelfinavir (NFV)-containing therapy. Earlier
      PI-naive patients (n=172) with NFV-containing therapy were therefore
      retrospectively studied. Plasma HIV RNA from 43 failing patients was sequenced.
      In addition, virus from the baseline was sequenced in 29 patients. Failure was
      defined as two consecutive measurements of viral load of >50 copies/ml after 6
      months treatment. Subtyping was done in most patients (n=118). At baseline, the
      V82A mutation was found in four PI-naive patients of whom two failed therapy
      exhibiting this mutation. At therapy failure, 17 of the 43 (40%) patients had
      primary PI mutations. In nine subjects, RTI-mutations only were found and 17
      patients had a wild-type virus. Patients with primary PI and/or RTI mutations had
      a higher viral load at failure than those who failed with wild-type virus. A
      surprisingly diverse pattern of primary PI mutations was seen: M46I (n=7), D30N
      (n=6), L90M (n=5), and V82A (n=4). Four patients exhibited more than one primary
      PI mutation. PI-naive patients in Sweden may harbor PI-resistant virus and
      resistance testing should be considered before treatment. Patients who fail NFV
      may develop the M46I mutation, which has been related earlier to mainly other PI.
      The diverse pattern of the evolved PI-mutations and the relative low occurrence
      of the D30N mutation in the material was unexpected and did not seem to be
      related to the viral subtype.

PMID- 15977243
TI  - Purification and partial characterization of R5, R5X4, and X4 HIV-1 subtype C
      envelope glycoproteins expressed in insect cells.
AB  - Biological properties of four recombinant HIV-1 subtype C envelope glycoproteins
      from viruses with different phenotypic characteristics (CCR5 and/or CXCR4
      utilizing) were investigated. The gp160 genes were cloned, expressed in
      Spodoptera frugiperda insect cells, purified, and their biological
      characteristics were examined. The conformational and functional integrity of the
      HIV-1 subtype C rgp160 was intact since they reacted with the A32, C11, IgG1b12,
      7B2, and 17b conformational dependant monoclonal antibodies (MAb), sCD4, and
      patient sera. Baculovirus derived rgp160 can be used for further structural,
      functional, antigenic, and immunological studies.

PMID- 15977244
TI  - Cervical squamous intra-epithelial changes and human papillomavirus infection in
      women infected with human immunodeficiency virus in Pune, India.
AB  - In view of the dual burden of HIV infection and cervical cancers in India, this
      study was undertaken to estimate the prevalence of Pap smear abnormalities and
      human papillomavirus infection among HIV-infected women. Consecutive HIV-infected
      women attending voluntary counseling testing clinics were enrolled. Written
      informed consent, demographic information, Pap smears, cervical swabs for HPV
      typing and a blood sample for CD4+ cell count were collected. Treatment for
      opportunistic and sexually transmitted infections and reproductive tract
      infections was provided. Women with Pap smear abnormality were referred for
      further intervention. Between January 2003 and May 2004, 287 HIV-infected women
      were enrolled. Pap smear abnormalities were seen in 6.3% women and were more
      common among women aged 30 and above (P=0.042) and those who had suffered from
      opportunistic infections (P=0.004). In multivariate analysis, Pap smear
      abnormalities were associated independently with opportunistic infections
      (P=0.02, AOR 3.8, 95% CI 1.2--11.5). Of the 100 random cervical specimens
      screened for HPV 16 and 18 genotypes, 33% (95 CI 23.9--43.1) were positive for
      HPV 16/18. Of the 122 patients who returned for a follow-up visit, 5 patients
      (4.1%) who did not have Pap smear abnormality at baseline, had developed Pap
      smear abnormality. The incidence of Pap smear abnormalities was 5.5 per 100
      person year of follow-up. In order to prevent thousands of deaths due to cervical
      cancer in India, there is a need for strengthening the Pap smear screening
      program and HPV vaccine development.

PMID- 15977246
TI  - Hepatitis C virus infection in 2,744 hemodialysis patients followed regularly at
      nine centers in Hiroshima during November 1999 through February 2003.
AB  - Patients on maintenance hemodialysis (HD) are at increased risk of infection with
      hepatitis C virus (HCV). A prospective follow-up study on HCV infection from
      November 1999 to February 2003 was conducted in nine hemodialysis (HD) units in
      Hiroshima. A total of 2,744 HD patients were surveyed regularly for HCV RNA in
      serum. The prevalence of HCV RNA decreased from 15.7% (262/1,664) on the first
      survey to 12.9% (242/1,882) in the last one (P<0.05). This decrease may be
      attributed to the inclusion of patients with a lower prevalence of HCV RNA
      compared to patients leaving dialysis centers (111/1,080 [10.3%] vs. 132/862
      [15.3%], P<0.01). During the 40 months of this study, 16 de novo HCV infections
      were documented in the nine HD units corresponding to an incidence of 0.33% per
      year. These cases included eight new HCV infections, three re-infections, and
      five infections that presumably occured in the window period when tested during
      the first survey. Our study shows that the annual incidence of de novo HCV
      infection during HD was 0.33%, and emphasizes the need for frequent serum HCV RNA
      testing and for stringent disinfection procedures in order to prevent the
      transmission of HCV in these settings.

PMID- 15977245
TI  - Intrahepatic cytokine profile in renal-transplant patients infected by hepatitis
      C virus.
AB  - In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related
      liver injury in renal-transplant patients, intra-hepatic cytokine profiles were
      examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA)
      concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon
      (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory
      cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor
      [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10,
      or IL-8 levels of expression according to liver-activity grade, liver-fibrosis
      stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype.
      However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta
      actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta
      actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir
      activity grades compared with those with A0 and A1 activity grades. There was a
      significant correlation between the duration of HCV infection and both TGF
      beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations
      (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased
      according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a
      significant correlation between the duration of HCV infection and liver fibrosis
      stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be
      predominant in patients with extensive fibrosis and activity scores, suggesting
      that it might be responsible for liver injury in renal transplant patients.

PMID- 15977247
TI  - Evolution over a 10 year period of the epidemiological profile of 1,726 newly
      diagnosed HCV patients in Belgium.
AB  - In order to evaluate the future burden of hepatitis C, there is a need to
      quantify the evolution with time of some crucial parameters such as disease
      frequency and age, modes of infection and infecting genotypes of patients
      presenting for the first time at consultation. The yearly evolution of these
      parameters was analyzed retrospectively in a cohort of 1,726 patients living in
      Belgium, who were diagnosed as hepatitis C virus (HCV) carriers by polymerase
      chain reaction (PCR) between 1992 and 2002. The epidemiological profile of HCV
      patients showed significant changes during this period. The number of new
      patients increased with time. The proportion of patients under 50 increased
      linearly at a rate of 3% per year. The rate of newly presenting patients infected
      by transfusion before 1990 decreased, but only by 2.7% per year. The proportion
      of intravenous (IV) drug users increased by 2.5% per year. Patients presenting
      "undefined" risk factors increased by 2.1% per year. Nosocomial acquisition of
      HCV infection exhibited a disturbing relative stability in time whereas dialysis
      tended to disappear as a cause of infection. There was a significant linear
      annual decrease of 2.3% in the frequency of genotype 1b, which was
      counterbalanced by a significant increase of 0.7% for genotype 1a and 1.1% for
      genotype 4. Genotypes 2 and 3 did not vary significantly with time. Such figures
      are useful for evaluating the epidemiological changes of C virus infection and
      for anticipating the future economical cost of hepatitis C treatment in the next
      few years.

PMID- 15977248
TI  - Recurrent mutations associated with isolation and passage of SARS coronavirus in
      cells from non-human primates.
AB  - Four clinical isolates of SARS coronavirus were serially passaged in two primate
      cell lines (FRhK4 and Vero E6). Viral genetic sequences encoding for structural
      proteins and open reading frames 6--8 were determined in the original clinical
      specimen, the initial virus isolate (passage 0) and at passages 5, 10, and 15.
      After 15 passages, a total of 15 different mutations were identified and 12 of
      them were non-synonymous mutations. Seven of these mutations were recurrent
      mutation and all located at the spike, membrane, and Orf 8a protein encoding
      sequences. Mutations in the membrane protein and a deletion in ORF 6--8 were
      already observed in passage 0, suggesting these amino acid substitutions are
      important in the adaptation of the virus isolate in primate cell culture. A
      mutation in the spike gene (residue 24079) appeared to be unique to adaptation in
      FRhK4 cells. It is important to be aware of cell culture associated mutations
      when interpreting data on molecular evolution of SARS coronavirus.

PMID- 15977249
TI  - Prevalence of complete resistance to at least two classes of antiretroviral drugs
      in treated HIV-1-infected patients: a French nationwide study.
AB  - The objective of the study was to estimate the prevalence of HIV-1 resistance to
      all drugs belonging to two or more antiretroviral drug (ARV) classes in treated
      patients in France. All genotyping assays performed in June 2001 and in November
      2002 by the ANRS resistance laboratory network were analyzed by the ANRS
      algorithm. The 17 and 21 centers of the ANRS network participating in the study
      in 2001 and 2002, respectively, genotyped the viruses in plasma of 456 and 529
      patients, respectively. In 2002, the proportions of patients harboring viruses
      fully resistant to one, two, and three ARV classes were 5.1%, 8.1%, and 2.5%,
      respectively. These results were similar to those obtained in 2001. In 2002,
      among the 56 patients with viruses completely resistant to at least two ARV
      classes, 98%, 96%, and 29% of patients had viruses with complete class resistance
      to NRTIs, NNRTIs, and PIs, respectively. Complete resistance to PIs was less
      frequent than full resistance to the other two ARV classes, and ritonavir-boosted
      amprenavir and lopinavir/r remained potentially active in respectively 71.4% and
      42.9% of these 56 patients. In 2001 and 2002, respectively 30% of the 65 patients
      and 24% of the 56 patients with viruses completely resistant to at least two ARV
      classes were at an advanced stage of HIV disease, with CD4(+) cell counts below
      200/microl and viral loads above 30 000 copies/ml. In France, the prevalence of
      HIV-1 viruses completely resistant to two or more ARV classes remained stable
      between 2001 and 2002. Resistance to RT inhibitors was more frequent than
      resistance to PIs in patients with viruses completely resistant to two or three
      classes of ARV.

PMID- 15977250
TI  - Development of a sensitive assay for the measurement of antibodies against heat
      shock protein binding protein 1 (HspBP1): increased levels of anti-HspBP1 IgG are
      prevalent in HIV infected subjects.
AB  - The 70 kDa heat shock protein (Hsp70) is generally considered to be an
      intracellular protein, however, there is evidence that Hsp70 can be found in the
      extracellular environment. Hsp70 and antibodies against Hsp70 have been reported
      in human serum. Recent evidence has shown that Hsp70 antibodies are elevated in
      HIV infected individuals. This study reports on the antibody levels against a co
      chaperone, HspBP1, that regulates Hsp70 activity. We have developed a solid-phase
      enzyme linked assay for the determination of anti-HspBP1 IgG antibodies. We
      report here that HspBP1 antibodies are present in human serum and the levels are
      elevated approximately twofold in HIV infected patients. There was no correlation
      between HspBP1 antibody levels and clinical parameters nor was there a relation
      between anti-Hsp70 levels and anti-HspBP1 levels. The presence of HspBP1
      antibodies in human serum suggests that the protein may also be present in the
      serum. The increased level of HspBP1 antibodies in HIV infected individuals
      suggests a relationship directly to the virus or indirectly to secondary
      consequences of HIV infection.

PMID- 15977251
TI  - Locally Addressable Electrochemical Patterning Technique (LAEPT) applied to
      poly(L-lysine)-graft-poly(ethylene glycol) adlayers on titanium and silicon oxide
      surfaces.
AB  - The protein-resistant polycationic graft polymer, poly(L-lysine)-g-poly(ethylene
      glycol) (PLL-g-PEG), was uniformly adsorbed onto a homogenous titanium surface
      and subsequently subjected to a direct current (dc) voltage. Under the influence
      of an ascending cathodic and anodic potential, there was a steady and gradual
      loss of PLL-g-PEG from the conductive titanium surface while no desorption was
      observed on the insulating silicon oxide substrates. We have implemented this
      difference in the electrochemical response of PLL-g-PEG on conductive titanium
      and insulating silicon oxide regions as a biosensing platform for the controlled
      surface functionalization of the titanium areas while maintaining a protein
      resistant background on the silicon oxide regions. A silicon-based substrate was
      micropatterned into alternating stripes of conductive titanium and insulating
      silicon oxide with subsequent PLL-g-PEG adsorption onto its surfaces. The surface
      modified substrate was then subjected to +1800 mV (referenced to the silver
      electrode). It was observed that the potentiostatic action removed the PLL-g-PEG
      from the titanium stripes without inducing any polyelectrolyte loss from the
      silicon oxide regions. Time-of-flight secondary ions mass spectroscopy and
      fluorescence microscopy qualitatively confirmed the PLL-g-PEG retention on the
      silicon oxide stripes and its absence on the titanium region. This method, known
      as "Locally Addressable Electrochemical Patterning Technique" (LAEPT), offers
      great prospects for biomedical and biosensing applications. In an attempt to
      elucidate the desorption mechanism of PLL-g-PEG in the presence of an electric
      field on titanium surface, we have conducted electrochemical impedance
      spectroscopy experiments on bare titanium substrates. The results showed that
      electrochemical transformations occurred within the titanium oxide layer; its
      impedance and polarization resistance were found to decrease steadily upon both
      cathodic and anodic polarization resulting in the polyelectrolyte desorption from
      the titanium surface.

PMID- 15977252
TI  - pH shift enhancement of Candida utilis pyruvate decarboxylase production.
AB  - Pyruvate decarboxylase (PDC) catalyses the synthesis of asymmetric carbinols,
      e.g., chiral precursors for pharmaceuticals such as ephedrine and
      pseudoephedrine. The production of PDC by Candida utilis in a minimal medium was
      improved by manipulating the pH during fermentation in a 5 L bioreactor. At an
      aeration rate of 0.1 vvm with a stirrer speed of 300 rpm at constant pH 6, a
      specific PDC activity of 141 U/g dry cell weight (DCW) was achieved (average of
      two fermentations +/-13%). By allowing the yeast to acidify the growth medium
      from pH 6 to 2.9, the final specific PDC activity increased by a factor of 2.7 to
      385 U/g DCW (average from 4 fermentations +/-16%). The effect of this pH drift on
      PDC production was confirmed by another experiment with a manual shift of pH from
      6 to 3 by addition of 5 M sulfuric acid. The final PDC activity was 392 U/g DCW
      (average from two fermentations +/-5%). However, experiments with constant pH of
      6, 5, 4, or 3 resulted in average specific activities of only 102 to 141 U/g DCW,
      suggesting that a transitional pH change rather than the absolute pH value was
      responsible for the increased specific PDC activity.

PMID- 15977253
TI  - Hydraulics of laboratory and full-scale upflow anaerobic sludge blanket (UASB)
      reactors.
AB  - Laboratory-scale upflow anaerobic sludge blanket (UASB) reactors are often used
      as test platforms to evaluate full-scale applications. However, for a given
      volume specific hydraulic loading rate and geometry, the gas and liquid flows
      increase proportionally with the cube root of volume. In this communication, we
      demonstrate that a laboratory-scale reactor had plug-flow hydraulics, while a
      full-scale reactor had mixed flow hydraulics. The laboratory-scale reactor could
      be modeled using an existing biochemical model, and parameters identified, but
      because of computational speed with plug-flow hydraulics, mixed systems are
      instead recommended for parameter identification studies. Because of the scaling
      issues identified, operational data should not be directly projected from
      laboratory-scale results to the full-scale design.

PMID- 15977254
TI  - Enhanced propionic acid fermentation by Propionibacterium acidipropionici mutant
      obtained by adaptation in a fibrous-bed bioreactor.
AB  - Fed-batch fermentations of glucose by P. acidipropionici ATCC 4875 in free-cell
      suspension culture and immobilized in a fibrous-bed bioreactor (FBB) were
      studied. The latter produced a much higher propionic acid concentration (71.8 +/-
      0.8 g/L vs. 52.2 +/- 1.1 g/L), indicating enhanced tolerance to propionic acid
      inhibition by cells adapted in the FBB. Compared to the free-cell fermentation,
      the FBB culture produced 20-59% more propionate (0.40-0.65 +/- 0.02 g/g vs. 0.41
      +/- 0.02 g/g), 17% less acetate (0.10 +/- 0.01 g/g vs. 0.12 +/- 0.02 g/g), and
      50% less succinate (0.09 +/- 0.02 g/g vs. 0.18 +/- 0.03 g/g) from glucose. The
      higher propionate production in the FBB was attributed to mutations in two key
      enzymes, oxaloacetate transcarboxylase and propionyl CoA: succinyl CoA
      transferase, leading to the production of propionic acid from pyruvate. Both
      showed higher specific activity and lower sensitivity to propionic acid
      inhibition in the mutant than in the wild type. In contrast, the activity of PEP
      carboxylase, which converts PEP directly to oxaloacetate and leads to the
      production of succinate from glucose, was generally lower in the mutant than in
      the wild type. For phosphotransacetylase and acetate kinase in the acetate
      formation pathway, however, there was no significant difference between the
      mutant and the wild type. In addition, the mutant had a striking change in its
      morphology. With a threefold increase in its length and approximately 24%
      decrease in its diameter, the mutant cell had an approximately 10% higher
      specific surface area that should have made the mutant more efficient in
      transporting substrates and metabolites across the cell membrane. A slightly
      lower membrane-bound ATPase activity found in the mutant also indicated that the
      mutant might have a more efficient proton pump to allow it to better tolerate
      propionic acid. In addition, the mutant had more longer-chain saturated fatty
      acids (C17:0) and less unsaturated fatty acids (C18:1), both of which could
      decrease membrane fluidity and might have contributed to the increased propionate
      tolerance. The enhanced propionic acid production from glucose by P.
      acidipropionici was thus attributed to both a high viable cell density maintained
      in the reactor and favorable mutations resulted from adaptation by cell
      immobilization in the FBB.

PMID- 15977255
TI  - IRB approval: consideration of power is essential for ethical approval.

PMID- 15977257
TI  - Neuromodulation.

PMID- 15977258
TI  - Improved surgical outcome by modification of porcine dermal collagen implant in
      abdominal wall reconstruction in rats.
AB  - AIM: We earlier showed in rats that fascial repair with Pelvicol, a porcine
      dermal collagen implant, was associated with a lesser inflammatory response but
      lower tensile strength in the early postoperative period as compared to Prolene.
      Herein we wanted to evaluate whether creation of pores in Pelvicol, facilitating
      ingrowth of fibrous tissue and vessels, would result in a higher tensile strength
      at d30 without compromising longer term results. METHODS: First tensile strength
      of Pelvicol modified with different pore sizes was evaluated ex vivo. In a second
      step, Pelvicol implants with pores were used to cover full-thickness abdominal
      wall defects in 36 rats. Implants were either Pelvicol (non-porous) or with pores
      of Phi : 0.7, 1.2, or 2.0 mm (n=6 each). Animals were sacrificed on d30 and 90 to
      evaluate the presence of herniation, infection, adhesions, change in thickness
      and tensile strength. Histopathology was performed to assess inflammatory
      response and collagen deposition. Data were compared to available data on Prolene
      implanted animals at same time points. RESULTS: Pelvicol with pore diameter of
      2.5 mm was significantly weaker ex vivo. Animals repaired with non-porous
      material did develop seroma (2/6) or clinical infection (1/6) whereas none in the
      other groups did. There was a trend for increasing tensile strength at 30 d with
      increasing pore diameter, being significant in the 2.0-mm pore size group. This
      difference disappeared by 90 d, where all materials were equally strong as
      Prolene. The foreign body reaction was less intense in a pore-size dependent
      manner, with more abundant neo-vascularization and collagen deposition passing
      through the pores. CONCLUSION: Creation of pores in Pelvicol promotes neo
      vascularization, collagen deposition, and fibrous tissue ingrowth, and at pore
      size 2.0 mm tensile strength was increased at d30 whereafter all materials had
      comparable strength.

PMID- 15977259
TI  - Standardization of terminology of pelvic floor muscle function and dysfunction:
      report from the pelvic floor clinical assessment group of the International
      Continence Society.

PMID- 15977260
TI  - A new minimally invasive procedure for pudendal nerve stimulation to treat
      neurogenic bladder: description of the method and preliminary data.
AB  - AIMS: Pudendal nerve stimulation has beneficial effects on numerous pelvic floor
      function impairments such as urinary and/or fecal incontinence, retention, and
      constipation. In preceding literature the implant technique required a fairly
      complex and invasive surgery, although recent advances with percutaneous
      placement of the lead through an introducer have made the procedure much less
      invasive. We performed staged procedure similar to that of sacral neuromodulation
      (SNM) to place tined lead near the pudendal nerve, using neurophysiological
      guidance that allowed accurate pudendal nerve stimulation through either perineal
      or posterior approach. We have named this approach chronic pudendal nerve
      stimulation (CPNS). METHODS: Fifteen neurogenic patients (eight male, seven
      female) with symptoms of urge incontinence due to neurogenic overactive bladder
      underwent CPNS. All patients had complete neurophysiological and urodynamic
      evaluation at baseline and follow-up and were asked to complete voiding and bowel
      diary for 7 days. RESULTS: During screening, average number of incontinent
      episodes per day decreased from 7+/-3.3 to 2.6+/-3.3 (P<0.02, paired t-test).
      Eight patients became continent, two improved by more than 88% (from 9 to 1 daily
      incontinence episode) and two patients reduced the number of incontinence
      episodes by 50%. The implantable pulse generator (IPG) was subsequently implanted
      in those 12 patients. Three patients without improvement did not continue to
      second stage. In implanted patients with 6 months follow-up, urodynamic
      evaluation showed an objective improvement in the maximum cystometric capacity
      which increased from 153.3+/-49.9 to 331.4+/-110.7 ml (P<0.01, paired t-test).
      The maximum pressure decreased from 66+/-24.3 to 36.8+/-35.9 cmH2O (P=0.059,
      paired t-test). Eight patients reported significant improvement in bowel
      function. CONCLUSION: Chronic pundedal nerve stimulation is feasible.
      Neurophysiological guidance is mandatory to place the lead near the pudendal
      nerve either using perineal or posterior approach. Further studies must be
      carried out to identify the best stimulation parameters and to verify the long
      term results.

PMID- 15977262
TI  - Aortic sinus-left atrial fistula after interventional closure of atrial septal
      defect.
AB  - A 3-year-old boy underwent interventional closure of an atrial septal defect
      using an Amplatzer septal occluder. After 4 weeks, an aortic sinus-to-left atrial
      fistula was detected by echocardiography in an asymptomatic child. The device was
      surgically explanted with fistula and atrial septal defect closure. Follow-up was
      uneventful.

PMID- 15977263
TI  - Assessment of the efficacy of phentolamine to prevent radial artery spasm during
      cardiac catheterization procedures: a randomized study comparing phentolamine vs.
      verapamil.
AB  - The objective of this study was to evaluate phentolamine as radial artery
      spasmolytic in transradial catheterization procedures. Radial artery spasm is a
      relatively frequent complication during transradial approach, causing patient
      discomfort or even making it impossible to continue the procedure. As radial
      artery spasm is mediated by the stimulation of alpha-adrenoreceptors, the use of
      the alpha-blocker phentolamine could make sense as spasmolytic. We designed a
      randomized double-blind study to compare phentolamine vs. verapamil, the standard
      spasmolytic agent. Five hundred patients (250 in each arm) submitted to a
      transradial cardiac catheterization were consecutively included and randomly
      assigned to receive 2.5 mg of verapamil or 2.5 mg of phentolamine after sheath
      insertion. Both vasodilator agents induced a significant radial artery diameter
      increase (from 2.22 +/- 0.53 to 2.48 +/- 0.57 mm, P < 0.001 for verapamil, and
      from 2.20 +/- 0.53 to 2.45 +/- 0.53 mm, P < 0.001 for phentolamine). However,
      verapamil was more efficacious to prevent radial artery spasm (13.2% compared
      with 23.2% in phentolamine-treated patients; P = 0.004). Follow-up (20 +/- 18
      days) evaluation of the radial artery patency by plestismography and pulse
      oximetry showed no differences between the two groups in the rate of radial
      occlusion (3.0% vs. 3.2% in verapamil and phentolamine treated patients,
      respectively). Phentolamine was an effective radial vasodilator agent, although
      it showed less ability to prevent radial artery spasm than verapamil. Radial
      artery occlusion rate was almost identical for both vasodilators. Thus,
      phentolamine could be a valid alternative to verapamil as a radial artery
      spasmolytic agent.

PMID- 15977264
TI  - Not so fast with that Novel use: does AVP = PDA?

PMID- 15977265
TI  - Effect of bare metal stenting on angiographic and clinical outcomes in diabetic
      and nondiabetic patients undergoing percutaneous coronary intervention of
      nonacute occluded coronary arteries: a report from the Total Occlusion Study of
      Canada (TOSCA).
AB  - The outcome after PTCA and coronary stenting of nonacute total coronary
      occlusions in the diabetic population is unknown. The main objective of the
      present report was to compare the angiographic and 1-year clinical outcomes in
      the diabetic and nondiabetic patients who were enrolled in the Total Occlusion
      Study of Canada (TOSCA), a prospective randomized controlled multicenter trial of
      primary stenting versus PTCA alone in nonacute native coronary artery occlusions.
      Of the 410 patients enrolled, 68 (16.5%) were diabetics. At 6-month follow-up,
      stenting resulted in significant improvement in angiographic outcome compared to
      PTCA alone in both diabetic and nondiabetic populations. Angiographic restenosis
      was significantly reduced by stenting in the nondiabetic population (69.3% vs.
      55.2%; P = 0.009). A reduction in restenosis of a similar magnitude was observed
      with stenting in the diabetic population (71.1% vs. 59.3%; P = NS). At 1-year
      clinical follow-up, composite adverse cardiac event rates were similar for both
      strategies regardless of diabetic status. Target vessel revascularization was
      reduced by stenting compared to PTCA in diabetics (20% vs. 31.6%) and
      nondiabetics (21.5% vs. 30%). A significant reduction for any vessel
      revascularization following stenting compared to PTCA was observed in the
      nondiabetic population (28.5% vs. 38.8%; P = 0.05) but not in the diabetic
      subgroup (36.7% vs. 42%; P = NS). In conclusion, stenting appeared to be superior
      to PTCA alone, resulting in similar magnitude of reduction in angiographic
      restenosis and target vessel revascularization rates in diabetics and
      nondiabetics. Restenosis rates in all groups remain high. This analysis forms an
      important background for future studies that are needed to examine the effect of
      stenting with drug-eluting stents in diabetics as well as nondiabetics with
      nonacute coronary occlusions.

PMID- 15977266
TI  - Novel use of the Amplatzer plug for closure of a patent ductus arteriosus.
AB  - We report the novel use of an Amplatzer vascular plug for closure of a large
      tubular patent ductus arteriosus in a small child.

PMID- 15977267
TI  - Use of polytetrafluoroethylene-covered stent for treatment of coronary artery
      aneurysm.
AB  - Coronary artery aneurysm is an uncommon occurrence, yet it is described more
      often today than in the past as coronary angiography is now routinely used for
      diagnosis and treatment of ischemic heart disease. However, there is no
      therapeutic consensus regarding this finding. We present a case of giant coronary
      artery aneurysm and review the literature on the use of polytetrafluoroethylene
      covered stents as a therapeutic option for this condition. Combined antiaggregant
      therapy is needed after the procedure. Randomized controlled trials of surgery
      versus covered stents are necessary to define the best treatment for large
      coronary artery aneurysms.

PMID- 15977268
TI  - Multiple comparisons between two groups on multiple Bernoulli outcomes while
      accounting for covariates.
AB  - The problem of adjusting for multiplicity when one has multiple outcome variables
      can be handled quite nicely by step-down permutation tests. More difficult is the
      problem when one wants an analysis of each outcome variable to be adjusted for
      some covariates and the outcome variables are Bernoulli. Special permutations can
      be used where the outcome vectors are permuted within each strata of the data
      defined by the levels of the (made discrete) covariates. This method is described
      and shown to control the familywise error rate at any prespecified level. The
      method is compared through simulation to a vector bootstrap approach, also using
      a step-down testing procedure. It is seen that the method using permutations
      within strata is superior to the vector bootstrap in terms of error control and
      power. The method is illustrated on a data set of 55 minor malformations of
      babies of diabetic and non-diabetic mothers.

PMID- 15977269
TI  - Estimation of age-specific sensitivity and sojourn time in breast cancer
      screening studies.
AB  - This study investigates statistical approaches to quantitatively describing the
      age effect on screening sensitivity and sojourn time distribution in breast
      cancer screening studies. Such an investigation is directly motivated by the need
      to understand the inherent relationships between age and these important
      quantities. We incorporate the age effect through generalized linear models under
      a progressive disease modelling framework and obtain the corresponding parameter
      estimators using the maximum likelihood method. Among a set of potential models,
      we use Akeike's information criterion and likelihood ratio test in model
      selection and inferences. Extensive simulation studies show that the estimators
      have reasonable accuracy and the model selection criterion works well. The
      proposed methods are illustrated using data from two large breast cancer
      screening trials. The results show that the screening sensitivity increases with
      age at screening examinations based on these two trials.

PMID- 15977270
TI  - Thermally stable nanocrystalline gamma-alumina layers with highly ordered 3D
      mesoporosity.

PMID- 15977271
TI  - 13C-labeled tyrosine residues as local IR probes for monitoring conformational
      changes in peptides and proteins.

PMID- 15977272
TI  - An inverse substrate orientation for the regioselective acylation of 3',5'
      diaminonucleosides catalyzed by Candida antarctica lipase B?
AB  - Candida antarctica lipase B (CAL-B) catalyzes the regioselective acylation of
      natural thymidine with oxime esters and also the regioselective acylation of an
      analogue, 3',5'-diamino-3',5'-dideoxythymidine with nonactivated esters. In both
      cases, acylation favors the less hindered 5'-position over the 3'-position by
      upto 80-fold. Computer modeling of phosphonate transition-state analogues for the
      acylation of thymidine suggests that CAL-B favors acylation of the 5'-position
      because this orientation allows the thymine ring to bind in a hydrophobic pocket
      and forms stronger key hydrogen bonds than acylation of the 3'-position. On the
      other hand, computer modeling of phosphonamidate analogues of the transition
      states for acylation of either the 3'- or 5'-amino groups in 3',5'-diamino-3',5'
      dideoxythymidine shows similar orientations and hydrogen bonds and, thus, does
      not explain the high regioselectivity. However, computer modeling of inverse
      structures, in which the acyl chain binds in the nucleophile pocket and vice
      versa, does rationalize the observed regioselectivity. The inverse structures fit
      the 5'-, but not the 3'-intermediate thymine ring, into the hydrophobic pocket,
      and form a weak new hydrogen bond between the O-2 carbonyl atom of the thymine
      and the nucleophile amine only for the 5'-intermediate. A water molecule might
      transfer a proton from the ammonium group to the active-site histidine. As a test
      of this inverse orientation, we compared the acylation of thymidine and 3',5'
      diamino-3',5'-dideoxythymidine with butyryl acyl donors and with isosteric
      methoxyacetyl acyl donors. Both acyl donors reacted at equal rates with
      thymidine, but the methoxyacetyl acyl donor reacted four times faster than the
      butyryl acyl donor with 3',5'-diamino-3',5'-dideoxythymidine. This faster rate is
      consistent with an inverse orientation for 3',5'-diamino-3',5'-dideoxythymidine,
      in which the ether oxygen atom of the methoxyacetyl group can form a similar
      hydrogen bond to the nucleophilic amine. This combination of modeling and
      experiments suggests that such lipase-catalyzed reactions of apparently close
      substrate analogues like alcohols and amines might follow different pathways.

PMID- 15977273
TI  - Design in silico, synthesis and binding evaluation of a carbohydrate-based
      scaffold for structurally novel inhibitors of matrix metalloproteinases.

PMID- 15977274
TI  - LanGT2 Catalyzes the First Glycosylation Step during landomycin A biosynthesis.
AB  - The glycosyltransferase LanGT2 is involved in the biosynthesis of the
      hexasaccharide side chain of the angucyclic antibiotic landomycin A. Its function
      was elucidated by targeted gene inactivation of lanGT2. The main metabolite of
      the obtained mutant was identified as tetrangulol (4), the progenitor of the
      landomycin aglycon (7). The lack of the sugar side chain indicates that LanGT2
      catalyzes the priming glycosyl transfer in the hexasaccharide biosynthesis: the
      attachment of a D-olivose to O-8 of the polyketide backbone. Heterologous
      expression of urdGT2 from S. fradiae Tu2717 in this mutant resulted in the
      production of a novel C-glycosylated angucycline (6).

PMID- 15977275
TI  - Metabolic engineering of aminocoumarins: inactivation of the methyltransferase
      gene cloP and generation of new clorobiocin derivatives in a heterologous host.
AB  - Aminocoumarin antibiotics are highly potent inhibitors of bacterial gyrase and
      represent a class of antibiotics that are very suitable for the generation of new
      compounds by metabolic engineering. In this study, the putative methyltransferase
      gene cloP in the biosynthetic gene cluster of clorobiocin was inactivated.
      Expression of the modified gene cluster in the heterologous host Streptomyces
      coelicolor M512 gave three new aminocoumarin antibiotics. The structures of the
      new compounds were elucidated by MS and 1H NMR, and their antibacterial
      activities were determined. All three compounds lacked clorobiocin's methyl group
      at 4-OH of the deoxysugar moiety, noviose. They differed from each other in the
      position of the 5-methylpyrrole-2-carbonyl group, which was found to be attached
      to either 2-OH, 3-OH or 4-OH of noviose. Attachment at 4-OH resulted in the
      highest antibacterial activity. This is the first time that an aminocoumarin
      antibiotic acylated at 4-OH in noviose has been detected.

PMID- 15977276
TI  - Converting Cytochrome b5 into cytochrome c-like protein.

PMID- 15977277
TI  - An enzyme module system for the synthesis of dTDP-activated deoxysugars from dTMP
      and sucrose.
AB  - A flexible enzyme module system is presented that allows preparative access to
      important dTDP-activated deoxyhexoses from dTMP and sucrose. The strategic
      combination of the recombinant enzymes dTMP-kinase and sucrose synthase (SuSy),
      and the enzymes RmlB (4,6-dehydratase), RmlC (3,5-epimerase) and RmlD (4
      ketoreductase) from the biosynthetic pathway of dTDP-beta-L-rhamnose was
      optimized. The SuSy module (dTMP-kinase, SuSy, +/-RmlB) yielded the precursor
      dTDP-alpha-D-glucose (2) or the biosynthetic intermediate dTDP-6-deoxy-4-keto
      alpha-D-glucose (3) on a 0.2-0.6 g scale with overall yields of 62 % and 72 %,
      respectively. A two-step strategy in which the SuSy module was followed by the
      deoxysugar module (RmlC and RmlD) resulted in the synthesis of dTDP-beta-L
      rhamnose (4; 24.1 micromol, overall yield: 35.9 %). Substitution of RmlC by DnmU
      from the dTDP-beta-L-daunosamine pathway of Streptomyces peucetius in this module
      demonstrated that DnmU acts in vitro as a 3,5-epimerase with 3 as substrate to
      yield 4 (32.2 mumol, overall yield: 44.7 %). Chemical reduction of 3 with NaBH4
      gave a mixture of the C-4 epimers dTDP-alpha-D-quinovose (6) and dTDP-alpha-D
      fucose (7) in a ratio of 2:1. In summary, the modular character of the presented
      enzyme system provides valuable compounds for the biochemical characterization of
      deoxysugar pathways playing a major role in microbial producers of antibiotic and
      antitumour agents.

PMID- 15977278
TI  - Oxidation states and CO ligand exchange kinetics in a self-assembled monolayer of
      a triruthenium cluster studied by in situ infrared spectroscopy.
AB  - Oxidation states and CO ligand exchange kinetics in a self-assembled monolayer
      (SAM) of an oxo-centered triruthenium cluster [Ru(3)(mu3-O)(mu
      CH3COO)6(CO)(L1)(L2)] (L1 = [(NC5H4)CH2NHC(O)(CH2)10S-]2, L2 = 4-methylpyridine)
      have been extensively investigated on the surface of a gold electrode in aqueous
      and nonaqueous solutions. The SAM exhibits three consecutive one-electron
      transfers and four oxidation states, which have been characterized by
      electrochemistry, in situ infrared spectroscopy, and in situ sum frequency
      generation (SFG) vibrational spectroscopy measurements. The original electron
      localized state of the Ru cluster center was changed to electron delocalization
      states by oxidation or reduction of the central Ru ions. These changes are
      revealed by the IR absorptions of the CO ligand and the bridging acetate ligands
      of the triruthenium cluster in the SAM. The IR absorptions of the two kinds of
      ligands are strongly dependent on the oxidation state of the Ru cluster center.
      One-electron oxidation of the central Ru ion in the SAM triggers a CO ligand
      liberation process. Solvent molecules may then occupy the CO site to result in a
      CO-free SAM. One-electron reduction of this CO-free SAM in a CO-saturated
      solution leads to re-coordination of the CO ligand into the SAM. Both processes
      can be precisely controlled by tuning the electrode potential. The kinetics of
      the CO exchange cycle in the SAM, including liberation and coordination, has been
      investigated by in situ IR and SFG measurements for the first time. The CO
      exchange cycle is significantly dependent on the temperature. The reaction rate
      greatly decreases with decreasing solution temperature, which is an important
      factor in the CO ligand exchange process. The activation energies of both CO
      liberation and coordination have been evaluated from the reaction rate constants
      obtained at various temperatures.

PMID- 15977279
TI  - Peptide electron transfer: more questions than answers.
AB  - Nature has specifically designed proteins, as opposed to DNA, for electron
      transfer. There is no doubt about the electron transfer within proteins compared
      with the uncertain and continuing debate about charge transfer through DNA.
      However, the exact mechanism of electron transfer within peptide systems has been
      a source of controversy. Two different mechanisms for electron transfer between a
      donor and an acceptor, electron hopping and bridge-assisted superexchange, have
      been proposed, and are supported by experimental evidence and theoretical
      calculations. Several factors were found to affect the kinetics of this process,
      including peptide chain length, secondary structure and hydrogen bonding.
      Electrochemical measurements of surface-supported peptides have contributed
      significantly to the debate. Here we summarize the current approaches to the
      study of electron transfer in peptides with a focus on surface measurements and
      comment on these results in light of the current and often controversial debate
      on electron transfer mechanisms in peptides.

PMID- 15977281
TI  - Are the hydrogen bonds of RNA (AU) stronger than those of DNA (AT)? A quantum
      mechanics study.
AB  - The intrinsic stability of Watson-Crick d(AT) and r(AU) hydrogen bonds was
      analyzed by employing a variety of quantum-mechanical techniques, such as energy
      calculations, determination of reactivity indexes, and analysis of electron
      density topology. The analyses were performed not only for equilibrium gas-phase
      geometries, but also on hundreds of conformations derived from molecular dynamics
      (MD) and database analysis. None of our results support the idea that r(AU)
      hydrogen bonds are intrinsically more stable than those of d(AT). Instead, our
      data are in accordance with the traditional view that the greater stability of
      RNA relative to DNA is attributable to a variety of effects (e.g., stacking,
      sugar puckering, solvation) rather than to a significant difference in the
      hydrogen bonding of DNA and RNA base pairs.

PMID- 15977280
TI  - Head-group size or hydrophilicity of surfactants: the major regulator of lipase
      activity in cationic water-in-oil microemulsions.
AB  - To determine the crucial role of surfactant head-group size in micellar
      enzymology, the activity of Chromobacterium Viscosum (CV) lipase was estimated in
      cationic water-in-oil (w/o) microemulsions of three different series of
      surfactants with varied head-group size and hydrophilicity. The different series
      were prepared by subsequent replacement of three methyl groups of
      cetyltrimethylammonium bromide (CTAB) with hydroxyethyl (1-3, series I),
      methoxyethyl (4-6, series II), and n-propyl (7-9, series III) groups. The
      hydrophilicity at the polar head was gradually reduced from series I to series
      III. Interestingly, the lipase activity was found to be markedly higher for
      series II surfactants relative to their more hydrophilic analogues in series I.
      Moreover, the activity remained almost comparable for complementary analogues of
      both series I and III, though the hydrophilicity was drastically different.
      Noticeably, the head-group area per surfactant is almost similar for comparable
      surfactants of both series I and III, but distinctly higher in case of series II
      surfactants. Thus the lipase activity was largely regulated by the surfactant
      head-group size, which plays the dominant role over the hydrophilicity. The
      increase in head-group size presumably allows the enzyme to attain a flexible
      conformation as well as increase in the local concentration of enzyme and
      substrate, leading to the higher efficiency of lipase. The lipase showed its best
      activity in the microemulsion of 6 probably because of its highest head-group
      size. Furthermore, the observed activity in 6 is 2-3-fold and 8-fold higher than
      sodium bis(2-ethyl-1-hexyl)sulfosuccinate (AOT) and CTAB-based microemulsions,
      respectively, and in fact highest ever in any w/o microemulsions.

PMID- 15977282
TI  - Site-isolated porphyrin catalysts in imprinted polymers.
AB  - A meso-tetraaryl ruthenium porphyrin complex having four polymerizable
      vinylbenzoxy groups (2) has been synthesized by reaction of pyrrole with 4
      (vinylbenzoxy)benzaldehyde and subsequent metalation with [Ru3(CO)12]. The
      porphyrin complex was immobilized by copolymerization with ethylene glycol
      dimethacrylate. The resulting polymer P2 was found to catalyze the oxidation of
      alcohols and alkanes with 2,6-dichloropyridine N-oxide without activation by
      mineral acids. Under similar conditions, the homogeneous catalyst 2 was
      completely inefficient. By using diphenylaminomethane and 1-aminoadamantane as
      coordinatively bound templates during the polymerization procedure, the
      molecularly imprinted polymers P3 and P4 have been synthesized. Compared with the
      polymer P2, the imprinted catalysts displayed a significantly increased activity
      with rate enhancements of up to a factor of 16.

PMID- 15977283
TI  - Mutasynthesis of rapamycin analogues through the manipulation of a gene governing
      starter unit biosynthesis.

PMID- 15977284
TI  - Dried foam films: self-standing, water-free, reversed bilayers of amphiphilic
      compounds.

PMID- 15977285
TI  - A framework for two-stage adaptive procedures to simultaneously test non
      inferiority and superiority.
AB  - In clinical trials it is often desirable to test for non-inferiority and for
      superiority simultaneously. For such a situation a two-stage adaptive procedure
      may be advantageous to a conventional single-stage procedure because a two-stage
      adaptive procedure allows the design of stage II, including the main study
      objective and sample size, to depend on the outcome of stage I. We propose a
      framework for designing two-stage adaptive procedures with a possible switch of
      the primary study objectives at the end of stage I between non-inferiority and
      superiority. The framework permits control of the type I error rate and
      specification of the unconditional powers and maximum sample size for each of non
      inferiority and superiority objectives. The actions at the end of stage I are
      predetermined as functions of the stage I observations, thus making specification
      of the unconditional powers possible. Based on the results at the end of stage I,
      the primary objective for stage II is chosen, and sample sizes and critical
      values for stage II are determined.

PMID- 15977286
TI  - Multiple imputation under Bayesianly smoothed pattern-mixture models for non
      ignorable drop-out.
AB  - Conventional pattern-mixture models can be highly sensitive to model
      misspecification. In many longitudinal studies, where the nature of the drop-out
      and the form of the population model are unknown, interval estimates from any
      single pattern-mixture model may suffer from undercoverage, because uncertainty
      about model misspecification is not taken into account. In this article, a new
      class of Bayesian random coefficient pattern-mixture models is developed to
      address potentially non-ignorable drop-out. Instead of imposing hard equality
      constraints to overcome inherent inestimability problems in pattern-mixture
      models, we propose to smooth the polynomial coefficient estimates across patterns
      using a hierarchical Bayesian model that allows random variation across groups.
      Using real and simulated data, we show that multiple imputation under a three
      level linear mixed-effects model which accommodates a random level due to drop
      out groups can be an effective method to deal with non-ignorable drop-out by
      allowing model uncertainty to be incorporated into the imputation process.

PMID- 15977287
TI  - Inter-rater reliability of nursing home surveys: a Bayesian latent class
      approach.
AB  - In the U.S., federal and state governments perform routine inspections of nursing
      homes. Results of the inspections allow government to generate fines for findings
      of non-compliance as well as allow consumers to rank facilities. The purpose of
      this study is to investigate the inter-rater reliability of the nursing home
      survey process. In general, the survey data involves 191 binary deficiency
      variables interpreted as 'deficient' or 'non-deficient'. To reduce the
      dimensionality of the problem, our proposed method involves two steps. First, we
      reduce the deficiency categories to sub-categories using previous nursing home
      studies. Second, looking at the State of Kansas specifically, we take the
      deficiency data from 1 year, and use Bayesian latent class analysis (LCA) to
      collapse the sub-categories to a binary variable. We evaluate inter-rater
      agreement using deficiency data from two separate survey teams on one facility, a
      matched-pair design. We evaluate the agreement of the two raters on binary data
      using the weights from the LCA. This allows a two-by-two contingency analysis
      using a Bayesian beta-binomial model. We elicit informative prior distributions
      from the nursing home providers. Together, with the experimental data, this
      provides a posterior distribution of the kappa agreement of the raters for
      nursing home deficiency citation data.

PMID- 15977288
TI  - Assay validation for left-censored data.
AB  - In laboratory validation studies, it is often important to assess agreement
      between two assays, based on different techniques. Oftentimes, both assays have
      lower limits of detection and thus measurements are left censored. For example,
      in studies of Human Immunodeficiency Virus (HIV), the branched DNA (bDNA) assay
      was developed to quantify HIV-1 RNA concentrations in plasma. Validation of newer
      assays, such as the RT-PCR (reverse transcriptase polymerase chain reaction)
      involves assessing agreement of measurements obtained using the two techniques.
      Both bDNA and RT-PCR assays have lower limits of detection and thus new
      statistical methods are needed for assessing agreement between two left-censored
      variables. In this paper, we present maximum likelihood and generalized
      estimating equations approaches to evaluate agreement between two assays that are
      subject to lower limits of detection. The concordance correlation coefficient is
      used as an agreement index. The methodology is illustrated using HIV RNA assay
      data collected as part of a long-term HIV cohort study.

PMID- 15977289
TI  - Diagnostics for assumptions in moderate to large simple clinical trials: do they
      really help?
AB  - In this article, primarily we look at a case study, where prior to conducting the
      major efficacy analysis, one performs a diagnostic test for assumptions, and acts
      upon the result if the diagnostic test rejects the assumptions. Specifically, we
      show by an example that a hybrid approach of using a diagnostic test for equality
      of variance in a two-sample t-test situation can adversely affect, rather than
      protect, the operating characteristics of the study. If this kind of hybrid
      approach fails in such a simple setting, analysts should be very cautious about
      using hybrid approaches in more complex analyses of efficacy. Secondarily, we
      present rationale as to why the classical tests (or slightly modified versions)
      can be viewed as asymptotically non-parametric, and can actually be more robust
      against failure of assumptions than rank tests. Readers are cautioned that this
      illustration is limited to efficacy analysis, and is not meant as a criticism of
      other analyses, such as modelling or exploratory ones.

PMID- 15977290
TI  - Bayesian modelling of imperfect ascertainment methods in cancer studies.
AB  - Tumour registry linkage, chart review and patient self-report are all commonly
      used ascertainment methods in cancer epidemiology. These methods are used for
      estimating the incidence or prevalence of different cancer types in a population,
      and for investigating the effects of possible risk factors for cancer. Tumour
      registry linkage is often treated as a gold standard, but in fact none of these
      methods is error free, and failure to adjust for imperfect ascertainment can lead
      to biased estimates. This is true both if the goal of the study is to estimate
      the properties of each ascertainment type, or if it is to estimate cancer
      incidence or prevalence from one or more of these methods. Although rarely
      applied in the literature to date, when cancer is ascertained by three or more
      methods, standard latent class models can be used to estimate cancer incidence or
      prevalence while adjusting for the estimated imperfect sensitivities and
      specificities of each ascertainment method. These models, however, do not account
      for variations in these properties across different cancer sites. To address this
      problem, we extend latent class methodology to include a hierarchical component,
      which accommodates different ascertainment properties across cancer sites. We
      apply our model to a data set of 169 lupus patients with three ascertainment
      methods and eight cancer types. This allows us to estimate the properties of each
      ascertainment method without assuming any to be a gold standard, and to calculate
      a standardized incidence ratio for cancer for lupus patients compared to the
      general population. As our data set is small, we also illustrate the effects as
      more data become available. We show that our model produces parameter estimates
      that are substantially different from the currently most popular method of
      ascertainment, which uses tumour registry data alone.

PMID- 15977291
TI  - A population-based Bayesian approach to the minimal model of glucose and insulin
      homeostasis.
AB  - The minimal model was proposed in the late 1970s by Bergman et al. (Am. J.
      Physiol. 1979; 236(6):E667) as a powerful model consisting of three differential
      equations describing the glucose and insulin kinetics of a single individual.
      Considering the glucose and insulin simultaneously, the minimal model is a highly
      ill-posed estimation problem, where the reconstruction most often has been done
      by non-linear least squares techniques separately for each entity. The minimal
      model was originally specified for a single individual and does not combine
      several individuals with the advantage of estimating the metabolic portrait for a
      whole population. Traditionally it has been analysed in a deterministic set-up
      with only error terms on the measurements. In this work we adopt a Bayesian
      graphical model to describe the coupled minimal model that accounts for both
      measurement and process variability, and the model is extended to a population
      based model. The estimation of the parameters are efficiently implemented in a
      Bayesian approach where posterior inference is made through the use of Markov
      chain Monte Carlo techniques. Hereby we obtain a powerful and flexible modelling
      framework for regularizing the ill-posed estimation problem often inherited in
      coupled stochastic differential equations. We demonstrate the method on
      experimental data from intravenous glucose tolerance tests performed on 19 normal
      glucose-tolerant subjects.

PMID- 15977293
TI  - Regression analysis of overdispersed correlated count data with subject specific
      covariates.
AB  - A robust likelihood approach for the analysis of overdispersed correlated count
      data that takes into account cluster varying covariates is proposed. We emphasise
      two characteristics of the proposed method: That the correlation structure
      satisfies the constraints on the second moments and that the estimation of the
      correlation structure guarantees consistent estimates of the regression
      coefficients. In addition we extend the mean specification to include within- and
      between-cluster effects. The method is illustrated through the analysis of data
      from two studies. In the first study, cross-sectional count data from a
      randomised controlled trial are analysed to evaluate the efficacy of a
      communication skills training programme. The second study involves longitudinal
      count data which represent counts of damaged hand joints in patients with
      psoriatic arthritis. Motivated by this study, we generalize our model to
      accommodate for a subpopulation of patients who are not susceptible to the
      development of damaged hand joints.

PMID- 15977292
TI  - A multistate Markov chain model for longitudinal, categorical quality-of-life
      data subject to non-ignorable missingness.
AB  - Quality-of-life (QOL) is an important outcome in clinical research, particularly
      in cancer clinical trials. Typically, data are collected longitudinally from
      patients during treatment and subsequent follow-up. Missing data are a common
      problem, and missingness may arise in a non-ignorable fashion. In particular, the
      probability that a patient misses an assessment may depend on the patient's QOL
      at the time of the scheduled assessment. We propose a Markov chain model for the
      analysis of categorical outcomes derived from QOL measures. Our model assumes
      that transitions between QOL states depend on covariates through generalized
      logit models or proportional odds models. To account for non-ignorable
      missingness, we incorporate logistic regression models for the conditional
      probabilities of observing measurements, given their actual values. The model can
      accommodate time-dependent covariates. Estimation is by maximum likelihood,
      summing over all possible values of the missing measurements. We describe options
      for selecting parsimonious models, and we study the finite-sample properties of
      the estimators by simulation. We apply the techniques to data from a breast
      cancer clinical trial in which QOL assessments were made longitudinally, and in
      which missing data frequently arose.

PMID- 15977294
TI  - FDR-controlling testing procedures and sample size determination for microarrays.
AB  - Microarrays are used increasingly to identify genes that are truly differentially
      expressed in tissues under different conditions. Planning such studies requires
      establishing a sample size that will ensure adequate statistical power. For
      microarray analyses, false discovery rate (FDR) is considered to be an
      appropriate error measure. Several FDR-controlling procedures have been
      developed. How these procedures perform for such analyses has not been evaluated
      thoroughly under realistic assumptions. In order to develop a method of
      determining sample sizes for these procedures, it needs to be established whether
      these procedures really control the FDR below the pre-specified level so that the
      determined sample size indeed provides adequate power. To answer this question,
      we first conducted simulation studies. Our simulation results showed that these
      procedures do control the FDR at most situations but under-control the FDR when
      the proportion of positive genes is small, the most likely scenarios. Thus, these
      existing procedures can overestimate the power and underestimate the sample size.
      Accordingly, we developed a simulation-based method to provide more accurate
      estimates for power and sample size.

PMID- 15977295
TI  - Group sequential clinical trials for longitudinal data with analyses using
      summary statistics.
AB  - Longitudinal endpoints are used in clinical trials, and the analysis of the
      results is often conducted using within-individual summary statistics. When these
      trials are monitored, interim analyses that include subjects with incomplete
      follow-up can give incorrect decisions due to bias by non-linearity in the true
      time trajectory of the treatment effect. Linear mixed-effects models can be used
      to remove this bias, but there is a lack of software to support both the design
      and implementation of monitoring plans in this setting. This paper considers a
      clinical trial in which the measurement time schedule is fixed (at least for pre
      trial design), and the scientific question is parameterized by a contrast across
      these measurement times. This setting assures generalizable inference in the
      presence of non-linear time trajectories. The distribution of the treatment
      effect estimate at the interim analyses using the longitudinal outcome
      measurements is given, and software to calculate the amount of information at
      each interim analysis is provided. The interim information specifies the analysis
      timing thereby allowing standard group sequential design software packages to be
      used for trials with longitudinal outcomes. The practical issues with
      implementation of these designs are described; in particular, methods are
      presented for consistent estimation of treatment effects at the interim analyses
      when outcomes are not measured according to the pre-trial schedule. Splus/R
      functions implementing this inference using appropriate linear mixed-effects
      models are provided. These designs are illustrated using a clinical trial of
      statin treatment for the symptoms of peripheral arterial disease.

PMID- 15977296
TI  - Pairwise multiple comparison adjustment in survival analysis.
AB  - Many clinical studies have as their endpoint the time until some event (such as
      death) occurs. Often in such studies researchers are interested in comparing
      several treatment or prognostic groups with one another in terms of their
      survival curves. When many such pairwise group comparisons are done, the chance
      of finding a false significance among all of the comparisons is inflated above
      the usual desired significance level. This paper investigates methods of
      adjusting the survival analysis for the number of comparisons being made. These
      methods are applied to a retrospective study conducted by the International Bone
      Marrow Transplant Registry and compared in a simulation study in terms of the
      power to detect actual differences in the survival curves between the groups.

PMID- 15977297
TI  - Planning a dose-response study with subject-specific doses.
AB  - This article is concerned with a dose-response study where the doses are subject
      specific. The motivating example is a study on the use of radioiodine in
      metastatic thyroid cancer where the dose is individualized for each subject based
      on pharmacokinetic models of clearance of the agent. The goal is to design a
      study that will estimate the probability of response within a specified
      precision. This setup does not fit into well-studied dose-response designs
      primarily because doses are subject-specific. Here the dose-response relationship
      is modelled using logistic regression and a second-order approximation to the
      asymptotic variance of the model parameters is developed. The resulting procedure
      is simple to apply and requires minimal assumptions regarding the distribution of
      the dose levels. Simulation studies establish that, for a reasonable range of
      parameter values, the approximation is reasonably accurate. A Monte Carlo
      procedure is developed as well for cases when the approximation performs poorly.
      The proposed method is applied to the thyroid cancer study, including elicitation
      of parameters and a sensitivity analysis. Computer code in SAS and R are provided
      in the Appendix.

PMID- 15977298
TI  - Functional form and risk adjustment of hospital costs: Bayesian analysis of a Box
      Cox random coefficients model.
AB  - While risk-adjusted outcomes are often used to compare the performance of
      hospitals and physicians, the most appropriate functional form for the risk
      adjustment process is not always obvious for continuous outcomes such as costs.
      Semi-log models are used most often to correct skewness in cost data, but there
      has been limited research to determine whether the log transformation is
      sufficient or whether another transformation is more appropriate. This study
      explores the most appropriate functional form for risk-adjusting the cost of
      coronary artery bypass graft (CABG) surgery. Data included patients undergoing
      CABG surgery at four hospitals in the midwest and were fit to a Box-Cox model
      with random coefficients (BCRC) using Markov chain Monte Carlo methods. Marginal
      likelihoods and Bayes factors were computed to perform model comparison of
      alternative model specifications. Rankings of hospital performance were created
      from the simulation output and the rankings produced by Bayesian estimates were
      compared to rankings produced by standard models fit using classical methods.
      Results suggest that, for these data, the most appropriate functional form is not
      logarithmic, but corresponds to a Box-Cox transformation of -1. Furthermore,
      Bayes factors overwhelmingly rejected the natural log transformation. However,
      the hospital ranking induced by the BCRC model was not different from the ranking
      produced by maximum likelihood estimates of either the linear or semi-log model.

PMID- 15977299
TI  - The investigation and correction of recall bias for an ordinal response in a case
      control study.
AB  - Consider a case-control study designed to investigate the possible association
      between development of a particular disease and the value of a putative risk
      factor measured on an ordinal scale. Let E denote a subject's true risk factor
      value and let E* denote a subject's recorded risk factor value. Misclassification
      bias occurs if conclusions reached regarding the relationship between disease
      status and E* do not also apply to the relationship between disease status and E.
      We propose a model for the conditional probability distribution of E* given E. We
      show how the model may be used to investigate misclassification bias in a
      validation study where measurements of E* and E are available for both cases and
      controls and apply the methods developed to data from a test-retest study of
      recall bias in the context of screening for hypertension. We also consider a
      situation where the validation study is carried out on a subset of the subjects
      within a larger case-control study. In that case, values for E* are available for
      all subjects but values for E are available only for those subjects included in
      the validation study. We show how correct likelihood-based inference concerning
      association between disease status and risk factor value may be carried out using
      all of the available data. A Monte Carlo study shows how the inclusion of a
      validation study leads to a correction of recall bias problems at the cost of an
      increased standard error for the estimated association parameter.

PMID- 15977300
TI  - Model mis-specification and overestimation of the intraclass correlation
      coefficient in cluster randomized trials.
AB  - Intraclass correlation coefficient (ICC) estimates must be provided when
      reporting the results of a cluster randomized trial. This study demonstrates that
      estimating this parameter with one-way ANOVA and an underlying mixed-effects
      statistical model leads to biased estimates. The bias depends on the effect size
      of the studied treatment.

PMID- 15977301
TI  - The probability of failing in detecting an infectious disease at entry points
      into a country.
AB  - In a group of N individuals, carrying an infection with prevalence pi, the exact
      probability P of failing in detecting the infection is evaluated when a
      diagnostic test of sensitivity s and specificity s' is carried out on a sample of
      n individuals extracted without replacement from the group. Furthermore, the
      minimal number of individuals that must be tested if the probability P has to be
      lower than a fixed value is determined as a function of pi. If all n tests result
      negative, confidence intervals for pi are given both in the frequentistic and
      Bayesian approach. These results are applied to recent data for severe acute
      respiratory syndrome (SARS). The conclusion is that entry screening with a
      diagnostic test is rarely an efficacious tool for preventing importation of a
      disease into a country.

PMID- 15977302
TI  - Small-sample performance of the robust score test and its modifications in
      generalized estimating equations.
AB  - The sandwich variance estimator of generalized estimating equations (GEE) may not
      perform well when the number of independent clusters is small. This could
      jeopardize the validity of the robust Wald test by causing inflated type I error
      and lower coverage probability of the corresponding confidence interval than the
      nominal level. Here, we investigate the small-sample performance of the robust
      score test for correlated data and propose several modifications to improve the
      performance. In a simulation study, we compare the robust score test to the
      robust Wald test for correlated Bernoulli and Poisson data, respectively. It is
      confirmed that the robust Wald test is too liberal whereas the robust score test
      is too conservative for small samples. To explain this puzzling operating
      difference between the two tests, we consider their applications to two special
      cases, one-sample and two-sample comparisons, thus motivating some modifications
      to the robust score test. A modification based on a simple adjustment to the
      usual robust score statistic by a factor of J/(J - 1) (where J is the number of
      clusters) reduces the conservativeness of the generalized score test. Simulation
      studies mimicking group-randomized clinical trials with binary and count
      responses indicated that it may improve the small-sample performance over that of
      the generalized score and Wald tests with test size closer to the nominal level.
      Finally, we demonstrate the utility of our proposal by applying it to a group
      randomized clinical trial, trying alternative cafeteria options in schools
      (TACOS).

PMID- 15977303
TI  - Towards gene therapy in prosthesis loosening: efficient killing of interface
      cells by gene-directed enzyme prodrug therapy with nitroreductase and the prodrug
      CB1954.
AB  - BACKGROUND: Loosening is a major complication in prosthesis surgery. To stabilize
      loosened orthopedic implants, the interface tissue surrounding the implant must
      be removed. As an alternative to manual removal, we explored the possibility of
      removing the tissue by gene-directed enzyme prodrug therapy. In the current study
      we investigated whether interface cells can be transduced by an HAdV-5 vector
      carrying the E.coli-derived nitroreductase gene and sensitized to the prodrug
      CB1954. METHODS: The gene transfer efficiency into cultures of diploid human
      interface cells was tested by exposing these cells to various concentrations of
      Ad.CMV.LacZ. Subsequently, we studied the susceptibility of cells to the
      NTR/CB1954 combination. RESULTS: X-gal staining of the Ad.CMV.LacZ-transduced
      cell cultures revealed that, at 200 plaque-forming units (pfu)/cell, 74% of the
      cells expressed the LacZ gene. Infection with an NTR construct in interface cell
      lines resulted in a 60-fold sensitization to the prodrug CB1954. In addition we
      observed that iotrolan (Isovist) contrast medium had no effect on viability of
      the cells. However, the presence of the contrast medium completely inhibited
      adenovirus-mediated gene transfer. CONCLUSIONS: From these data we conclude that
      HAdV-5-based vectors carrying nitroreductase can be used to sensitize interface
      tissue. Instead of contrast medium the clinical protocol will use an alternative
      visualization procedure.

PMID- 15977304
TI  - Is insulin resistance caused by defects in insulin's target cells or by a
      stressed mind?
AB  - The importance of understanding insulin action is emphasized by the increasing
      prevalence of insulin resistance in various populations and by the fact that it
      plays an important pathophysiological role in many common disorders, for example,
      diabetes, obesity, hypertension and dyslipidemia. The primary factors responsible
      for the development of insulin resistance are so far unknown, although both
      genetic and environmental factors are involved. The genetic defects responsible
      for the common forms of insulin resistance, for example, in type 2 diabetes, are
      largely unidentified. Some studies from our group as well as by other
      investigators suggest that cellular insulin resistance is reversible and that it
      may be secondary to factors in the in vivo environment. These may include insulin
      antagonistic action of hormones like catecholamines, glucocorticoids, sex
      steroids and adipokines as well as dysregulation of autonomic nervous activity
      and they could contribute to the early development of insulin resistance. Some of
      these factors can directly impair glucose uptake capacity and this might be due
      to alterations in key proteins involved in insulin's intracellular signaling
      pathways. This article briefly summarizes proposed mechanisms behind cellular and
      whole-body insulin resistance. In particular, we question the role of intrinsic
      defects in insulin's target cells as primary mechanisms in the development of
      insulin resistance in type 2 diabetes and we suggest that metabolic and
      neurohormonal factors instead are the main culprits.

PMID- 15977305
TI  - Life course determinants of insulin secretion and sensitivity at age 50 years:
      the Newcastle thousand families study.
AB  - BACKGROUND: Suboptimal nutrition during fetal life and infancy is suggested to
      increase insulin resistance in adulthood. This study investigated the proportion
      of variance in insulin secretion and resistance accounted for by factors
      operating at different stages of life using a cohort of all 1142 births in the
      city of Newcastle, UK in May and June 1947. METHODS: Detailed information was
      collected prospectively during childhood, including birth weight, growth and
      socio-economic circumstances. At age 50, 412 study members attended for clinical
      examination. Fasting and 30-min plasma insulin and glucose levels were determined
      and HOMA-IR and insulin secretion derived. RESULTS: Birth weight was not a
      significant predictor of HOMA-IR after adjustment for percent body-fat and waist
      hip ratio. Duration of breastfeeding was significantly negatively associated with
      HOMA-IR in men. For both genders, fetal life explained directly little variation
      in either HOMA-IR or insulin secretion (0.1-5.6%). Compared to early life, adult
      lifestyle and body composition directly explained larger proportions of the
      variances for insulin secretion and HOMA-IR for men (11 and 22% respectively) and
      women (5.9 and 34%). CONCLUSIONS: Insulin secretion is largely unexplained by
      these data. For insulin resistance, the evidence suggests a limited impact of
      early life and a larger impact of adult factors.

PMID- 15977310
TI  - Simazine dynamics in a vineyard soil at Casablanca valley, Chile.
AB  - Field dissipation, soil movement and laboratory leaching studies were performed
      to elucidate the effect of two rainfall amounts in the behaviour and
      environmental fate of simazine under climatic conditions at Casablanca Valley,
      Chile. Dissipation and soil movement were studied in a field vineyard with a
      sandy loam soil (Inceptisol; 74.08% sand; 14.87% silt and 11.04% clay). Simazine
      was applied to bare soil at 2.0 kg AI ha(-1), and its concentration was measured
      using immunoassay (ELISA) at 0, 10, 20, 40 and 90 days after application under
      two rainfall amounts, natural field conditions (39 mm) and modified conditions
      (39 + 180 mm). Simazine leaching was studied using soil core PVC lysimeters (0.9
      m height; 0.22 m diameter). Field dissipation data were adjusted with a bi
      exponential model. Half-life (DT(50)) values varied between 31.3 (+/-2.5) and
      19.0 (+/-4.2) days under natural and modified conditions, respectively. Simazine
      K(d) varied from 0.42 to 2.15 (K(oc) 32.6-216.2) in the soil profile. Simazine
      was detected at a 90-cm soil depth in concentrations of 0.0085 (+/-0.0043) mg kg(
      1) and 0.0321 (+/-0.001) mg kg(-1) under field and modified conditions,
      respectively. The maximum simazine leachate concentrations were 0.013 (+/
      0.00084) mg litre(-1) (0.012% of total applied simazine) and 0.0084 (+/-0.00082)
      mg litre(-1) (0.11% of total applied simazine) for field and modified conditions
      respectively. These data indicate that water quantity has a significant effect on
      the DT(50) and the amount of simazine that moved through the soil profile, but
      not on the soil depth reached by this herbicide.

PMID- 15977311
TI  - Relationship between nuchal translucency thickness and prevalence of major
      cardiac defects in fetuses with normal karyotype.
AB  - OBJECTIVE: To define the prevalence of major cardiac defects according to nuchal
      translucency (NT) thickness at the 11 to 13 + 6-week scan in fetuses with normal
      karyotype. METHODS: Specialist fetal echocardiography was carried in 6921 fetuses
      with normal or presumed normal karyotype at a median gestation of 20 (range 12
      35) weeks. The indications for fetal echocardiography were increased NT thickness
      (n = 3444), detailed second-trimester scan either for assessment of risk of
      chromosomal abnormalities (n = 2980) or previous or family history of fetal
      defects (n = 497). The cardiac defects were grouped into six functional
      categories: septal defect, left inflow obstruction, right inflow obstruction,
      left outflow obstruction, right outflow obstruction and other. RESULTS: Major
      cardiac defects were identified in 132 (19.1 per 1000) fetuses and the prevalence
      increased with fetal NT thickness from 4.9 per 1000 in those with NT below the
      median, to 8.7 for NT between the median and less than the 95th centile, 18.2 for
      NT between the 95th and 99th centiles, and exponentially thereafter to 35.2, 64.4
      and 126.7 for respective NTs of 3.5-4.4 mm, 4.5-5.4 mm and > or = 5.5 mm. There
      was no obvious difference in the distribution of NT in the different types of
      cardiac defects. CONCLUSIONS: The prevalence of major cardiac defects increases
      exponentially with fetal NT thickness and in fetuses with NT of 3.5 mm or more it
      is higher than in pregnancies with a family history of cardiac defects.

PMID- 15977312
TI  - Composite prostheses used to repair abdominal wall defects: physical or chemical
      adhesion barriers?
AB  - In a composite prosthesis, the component placed at the peritoneal interface takes
      the form of a physical or chemical barrier. In this experimental study performed
      on the white New Zealand rabbit, several composites were examined to establish
      the effectiveness of these barriers at impeding adhesion formation. The
      biomaterials tested were two polypropylene prostheses (PP) with the physical
      barriers of expanded polytetrafluoroethylene or polyurethane (PP + ePTFE and PP +
      PU) and two prostheses (one polyester and the other PP) with the absorbable
      chemical barriers of polyethylene glycol/glycerol and hyaluronate, respectively
      (PO + gl and PP + hy). The composites were used to repair 7 x 5 cm defects
      created in the abdominal wall of the animals by placing the implant in contact
      with the visceral peritoneum and the subcutaneous tissue and fixing it to
      recipient tissue by 4/0 polypropylene running suture. Fourteen days after surgery
      the animals were sacrificed and specimens were taken for light microscopy and
      scanning electron microscopy. Adhesions developing at the prosthesis/visceral
      peritoneal interface were quantified. All the prostheses induced optimal
      mesothelialization. Composites with physical barriers behaved similarly in terms
      of provoking adhesions. However, the prostheses with chemical barriers differed
      in their effectiveness at preventing adhesions. Overall, the best results were
      obtained with the PP + PU composite.

PMID- 15977313
TI  - The role of culture in families' treatment decisions for children with autism
      spectrum disorders.
AB  - There is little information available about how and why parents of children with
      autism spectrum disorders (ASD) make decisions regarding which of the many
      available treatments to implement with their children. Given the lack of
      available information regarding treatment efficacy, it is likely that parents'
      beliefs about child development, interpretation of the symptoms of ASD, its
      etiology and course, and their experiences with the health system influence
      treatment decisions. This article addresses these issues within the context of
      cultural influences. We review the small body of existing literature regarding
      cultural influences on decisions regarding ASD and draw implications for the
      study and treatment of ASD from the larger body of literature on culture and
      other health conditions of childhood. In addition to examining the potential for
      differences in clinical presentation by culture and different experiences with
      the healthcare system, we use Kleinman's framework of questions for understanding
      the role of culture in the interpretation and treatment of ASD. These questions
      address interpretation of symptoms and beliefs about their cause, course, and
      treatment. Finally, we present specific language for clinicians to use in
      discussion with families with different cultural beliefs about the use of less
      traditional treatment strategies.

PMID- 15977314
TI  - Occupational therapy using a sensory integrative approach for children with
      developmental disabilities.
AB  - This article provides an introduction and overview of sensory integration theory
      as it is used in occupational therapy practice for children with developmental
      disabilities. This review of the theoretical tenets of the theory, its historical
      foundations, and early research provides the reader with a basis for exploring
      current uses and applications. The key principles of the sensory integrative
      approach, including concepts such as "the just right challenge" and "the adaptive
      response" as conceptualized by A. Jean Ayres, the theory's founder, are presented
      to familiarize the reader with the approach. The state of research in this area
      is presented, including studies underway to further delineate the subtypes of
      sensory integrative dysfunction, the neurobiological mechanisms of poor sensory
      processing, advances in theory development, and the development of a fidelity
      measure for use in intervention studies. Finally, this article reviews the
      current state of the evidence to support this approach and suggests that
      consensual knowledge and empirical research are needed to further elucidate the
      theory and its utility for a variety of children with developmental disabilities.
      This is especially critical given the public pressure by parents of children with
      autism and other developmental disabilities to obtain services and who have
      anecdotally noted the utility of sensory integration therapy for helping their
      children function more independently. Key limiting factors to research include
      lack of funding, paucity of doctorate trained clinicians and researchers in
      occupational therapy, and the inherent heterogeneity of the population of
      children affected by sensory integrative dysfunction. A call to action for
      occupational therapy researchers, funding agencies, and other professions is made
      to support ongoing efforts and to develop initiatives that will lead to better
      diagnoses and effective intervention for sensory integrative dysfunction, which
      will improve the lives of children and their families.

PMID- 15977316
TI  - Placebo effects in developmental disabilities: implications for research and
      practice.
AB  - Recent clinical trials of secretin in children with autism showed robust placebo
      effects and no benefit of secretin over placebo. This article explores the
      reasons for the observed placebo effects, focusing on the heightening of positive
      expectancy by media attention and by the sensory experiences associated with
      intravenous injections. Comparisons are drawn with research involving other novel
      treatments and other clinical populations of children with developmental
      disabilities and neurobehavioral disorders. Research regarding mechanisms of
      placebo effects is reviewed, including patient and clinician attributes,
      expectancy effects, participation effects, changes in caregiver behavior, and
      conditioning. New evidence regarding the biological basis of placebo effects is
      briefly presented. Since placebo effects are ubiquitous and may operate by a
      variety of mechanisms, research design is critical in designing clinical trials
      and in evaluating other outcomes research. Measurement issues important for
      research in developmental disabilities are emphasized. Ethical concerns have been
      raised regarding the use of placebo in clinical research, but current analysis
      suggests that placebo controls are necessary and defensible on ethical grounds,
      if certain conditions are met. The study of placebo effects ("placebology") holds
      great promise as a new area of research in therapeutics. The author's research in
      the potential augmentation of stimulant effects in children with attention
      deficit/hyperactivity disorder (ADHD) by adding placebo in open label is briefly
      presented. The placebo has always been integral to the practice of medicine, but
      advances in scientific medicine and medical ethics have diminished the role and
      use of placebo in practice. An innovative approach to the ethical use of placebo
      is proposed.

PMID- 15977315
TI  - Complementary and alternative therapies for Down syndrome.
AB  - In their role as committed advocates, parents of children with Down syndrome have
      always sought alternative therapies, mainly to enhance cognitive function but
      also to improve their appearance. Nutritional supplements have been the most
      frequent type of complementary and alternative therapy used. Cell therapy,
      plastic surgery, hormonal therapy, and a host of other therapies such as massage
      therapy have been used. There is a lack of well-designed scientific studies on
      the use of alternative therapies in individuals with Down syndrome. Antioxidants
      hold theoretical promise for treatment of the cognitive, immune, malignancy, and
      premature aging problems associated with Down syndrome. Medications for treatment
      of Alzheimer's disease may also result in benefit for the population of
      individuals with Down syndrome.

PMID- 15977317
TI  - Introduction: novel therapies in developmental disabilities--hope, reason, and
      evidence.
AB  - Complementary and alternative medicine (CAM) is used both alongside
      (complementary) and as a substitute for (alternative) conventional therapies.
      Although CAM use is reported to be high among children with typical development,
      reported rates for CAM use to address symptoms of children with developmental
      disabilities may be higher. Increased use in this population may relate to hope
      for amelioration of symptoms, concerns regarding side effects of conventional
      treatments, and a need on the part of families to participate in decision making
      regarding their child's care. Primary health care providers may find that the
      child's needs are best served when they maintain a dialogue with families to
      evaluate the evidence supporting novel therapies. Interventions need to be
      assessed in an evidence based fashion whether or not they are initially preceived
      as CAM. This issue of Mental Retardation and Developmental Disabilities Research
      Reviews contains reviews of CAM used to treat several developmental disabilities
      as well as some broader discussions related to the determinants of CAM use,
      current efforts to evaluate novel therapies, and how to consider the possibility
      of placebo effects.

PMID- 15977318
TI  - Old and new controversies in the alternative treatment of attention-deficit
      hyperactivity disorder.
AB  - Use of complementary and alternative medicine (CAM) for treatment of attention
      deficit hyperactivity disorder (ADHD) has become widespread in both referral and
      primary care populations. We review the purported mechanism of action and
      available evidence for selected CAM therapies for ADHD. Enduring controversies,
      such as elimination of artificial food additives, colors, and/or preservatives;
      the effect of sugar on behavior in children; and the use of EEG biofeedback, have
      been well studied but lack support as effective sole treatments for ADHD. The
      initial evidence for some emerging CAM therapies, such as essential fatty acid
      supplementation, yoga, massage, homeopathy, and green outdoor spaces, suggests
      potential benefits as part of an overall ADHD treatment plan. More rigorously
      designed studies are needed to evaluate their effectiveness as single therapy for
      ADHD.

PMID- 15977319
TI  - Novel treatments for autistic spectrum disorders.
AB  - In no area of developmental pediatric practice is there more controversy
      regarding the choice of treatment than related to children with autistic spectrum
      disorders (ASD). Complementary and alternative medical therapies (CAM) are often
      elected because they are perceived as treating the cause of symptoms rather than
      the symptoms themselves. CAM used for autism can be divided by proposed
      mechanism: immune modulation, gastrointestinal, supplements that affect
      neurotransmitter function, and nonbiologic intervention. Secretin as a therapy
      for autism is discussed as an example of how a clinical observation rapidly grew
      to a widespread treatment before well-designed studies demonstrated absence of
      effect. The plausibility for behavioral effect was not substantiated by clinical
      studies. CAM used for treatment of autism is examined in terms of rationale,
      evidence of efficacy, side effects, and additional commentary. Families and
      clinicians need access to well-designed clinical evidence to assist them in
      choice of therapies.

PMID- 15977320
TI  - Complementary and alternative therapies for cerebral palsy.
AB  - The optimal practice of medicine includes integrating individual clinical
      expertise with the best available clinical evidence from systematic research.
      This article reviews nine treatment modalities used for children who have
      cerebral palsy (CP), including hyperbaric oxygen, the Adeli Suit, patterning,
      electrical stimulation, conductive education, equine-assisted therapy,
      craniosacral therapy, Feldenkrais therapy, and acupuncture. Unfortunately, these
      modalities have different degrees of published evidence to support or refute
      their effectiveness. Uncontrolled and controlled trials of hippotherapy have
      shown beneficial effects on body structures and functioning. Studies of
      acupuncture are promising, but more studies are required before specific
      recommendations can be made. Most studies of patterning have been negative and
      its use cannot be recommended. However, for the other interventions, such as
      hyperbaric oxygen, more evidence is required before recommendations can be made.
      The individual with CP and his or her family have a right to full disclosure of
      all possible treatment options and whatever knowledge currently is available
      regarding these therapies.

PMID- 15977321
TI  - The defective En-I102 element encodes a product reducing the mutability of the
      En/Spm transposable element system of Zea mays.
AB  - Genetic and molecular analysis has revealed a specific En-element of deletion
      derivative (En-I102) which reduces En/Spm-induced mutability. In the presence of
      En-I102 the excision frequency of both the autonomous En-1 element and the
      inhibitor element Spm-I5719A is reduced and excision occurs later in development.
      The 3697 bp long En-I102 element is derived from En-1 by an internal deletion of
      4590 bp removing nucleotides 1862-6451. The promoter at the left end and
      sequences required for polyadenylation are retained in En-I102. It is transcribed
      to yield predominantly a 1.8 kb poly(A) RNA. cDNA analysis of this transcript
      indicated that it contains the coding capacity for a 386 amino acid polypeptide.
      This polypeptide shares homology with En/Spm encoded functions and we suggest
      that it interferes with transposition at the protein level.

PMID- 15977322
TI  - [47th annual meeting of the Japan Geriatrics Society. Tokyo, Japan.  June 15-17,
      2005. Abstracts].

PMID- 15977323
TI  - [High-dose chemotherapy and stem-cell in patients with breast cancer].
AB  - BACKGROUND: The treatment of breast cancer patients with high-dose chemotherapy
      and stem-cell support is still highly controversial. The elucidation of its
      clinical benefit awaits the maturation of on-going clinical trials. METHODS:
      Patients with chemotherapy-sensitive metastatic or locally advanced disease and
      patients with stage II/III disease and at least four positive axillary lymph
      nodes in the initial surgical specimen were eligible for transplantation.
      RESULTS: Fifty-five women underwent transplantation between 1994 and 2000. For
      the 19 women with metastatic disease, the median time to progression was seven
      month and survival 28 months. Only two patients are progression-free, at 48 and
      77 months, both with supraclavicular and/or cervical lymph node-only disease. For
      the 36 women with stage II/III disease, the median time to progression and
      survival were both 65 months -19 are alive, 18 disease-free. Among the subgroup
      of 23 patients with 10 or more positive axillary nodes, the five-year event-free
      survival was 57%. CONCLUSION: The clinical benefit of stem-cell transplantation
      for metastatic breast cancer is limited since the time to progression and
      survival after transplantation is similar to those reported in patients with
      newly diagnosed metastases and treated with conventional-dose chemotherapy.
      However, in patients with high-risk stage II/III disease the time to progression
      is longer than that reported for similar patients treated with conventional
      systemic treatment. These results are similar to previous reports in the
      literature.

PMID- 15977324
TI  - Anti-babesial compounds from Curcuma zedoaria.
AB  - Anti-babesial activity was confirmed in an extract of the bark of Curcuma
      zedoaria. The active ingredients were isolated, and their chemical structures
      were determined to be zedoalactones A, B, and C based on spectral data.
      Zedoalactone C is a hitherto unreported compound. The IC50 vales of these active
      compounds against Babesia gibsoni were compared with a standard drug, diminazene
      aceturate. The IC50 value of diminazene aceturate was 0.6 microg/mL, while those
      of zedoalactones A, B, and C were 16.5, 1.6 and 4.2 microg/mL, respectively.

PMID- 15977325
TI  - Okra-leaf accessions of the upland cotton (Gossypium hirsutum L.): genetic
      variability in agronomic and fibre traits.
AB  - Okra-leaf types of the upland cotton have the potential to be competitive to the
      normal-leaf types in yield and fibre quality, in addition to its potential
      resistance to insect pests and drought. Okra-leaf cotton accessions, collected at
      Cotton Research Institute, Faisalabad, Pakistan, were evaluated in respect of
      genetic variance and relative performance in half- and full-sib crosses
      (combining ability) for 2 years. Variation due to parents x years interaction was
      significant for lint percentage, seed weight and earliness index, resulting in
      moderately low but significant genetic variance across environments (years) for
      these traits. Interaction of environment with general combining ability was
      significant for seed yield, seed weight, and earliness index. General combining
      ability variation, contributed by females and males together, accounted for 71%
      of the total variation available for seed cotton yield, 60% of that for seed
      weight and height to node ratio each, and 75% of that for earliness index.
      Specific combining ability variation accounted for 85% and 51% of the total
      variation available for lint percentage and staple length, respectively. The
      contribution of female parents to general combining ability variation was higher
      than that of male parents for seed cotton yield, seed weight, height to node
      ratio, and earliness index. Okra-leaf accessions HR-VO-MS and HR107-NH were
      predicted to produce progenies having high yield, HR109-RT high lint percentage,
      while HR100-Okra, Gambo-Okra and HR-VO-1 were predicted to impart early crop
      maturity to their progenies by reason of their good general combining ability for
      these traits. The results also provided evidence that genes controlling high
      yield in HR-VO-MS and HR107-NH were different from those controlling high yield
      in HR109-RT. The set of genes controlling the high earliness index in HR100-Okra
      and that in HR-VO-MS also appeared to differ in expression.

PMID- 15977326
TI  - Location and life: how Stenberg v. Carhart undercut Roe v. Wade.

PMID- 15977327
TI  - Air Force women's access to abortion services and the erosion of 10 U.S.C.,
      section 1093.

PMID- 15977329
TI  - An unjust act: the schizophrenic state of maturity and culpability in juvenile
      justice and minor abortion rights law; recent trends in Virginia and nationally.

PMID- 15977330
TI  - Federally funded stem cell research: a good deal for the taxpayer and consumer.

PMID- 15977332
TI  - Cloning human beings and the consumer of the future: a worthwhile endeavor or a
      nightmare come true?

PMID- 15977331
TI  - Single genes from Agrobacterium rhizogenes influence plant development.
AB  - The combined expression of the rol A, B, and C loci of Agrobacterium rhizogenes
      Ri-plasmids establishes, in transgenic tobacco plants, a pathological state
      called hairy-root syndrome. However, when expressed separately they provoke
      distinct developmental abnormalities characteristic for each rol gene. Moreover,
      changes in their mode of expression obtained by replacing the promoters of the
      rol B and C genes with the cauliflower mosaic virus 35S promoter elicit new and
      distinct developmental patterns. These results indicate that the different rol
      gene products have either different targets, or have a qualitatively different
      effect on the same target. The target(s) must be involved in the control of plant
      development. Although each of the three rol genes are independently able to
      promote root formation in tobacco, efficient root initiation and growth is best
      achieved through the combined activities of more than a single rol gene. Models
      explaining the biological effects of A. rhizogenes-derived TL-DNA genes are
      discussed.

PMID- 15977333
TI  - Patent law--balancing profit maximization and public access to technology.
AB  - This article addresses the contemporary issue of balancing the need for patent
      protection for intellectual property with the resulting restriction of public
      access to new technology. The author argues that patent law protects private
      property rights rather than creating monopolies. Additionally, the author
      discusses how restricting access to patented technology, such as pharmaceuticals,
      can affect public health problems, such as the HIV/AIDS epidemic in developing
      nations. The author then concludes with some proposals for making patented
      technology available to people in developing nations who need access to such
      technology but who are unable to afford its high costs due to patent protection.

PMID- 15977334
TI  - In vivo import of plastocyanin and a fusion protein into developmentally
      different plastids of transgenic plants.
AB  - Transgenic tomato plants that constitutively express a foreign plastocyanin gene
      were used to study protein transport in different tissues. Normally expression of
      endogenous plastocyanin genes in plants is restricted to photosynthetic tissues
      only, whereas this foreign plastocyanin protein is found to be present in all
      tissues examined. The protein is transported into the local plastids in these
      tissues and it is processed to the mature size. We conclude that plastids of
      developmentally different tissues are capable of importing precursor proteins
      that are normally not found in these tissues. Most likely such plastids, though
      functionally and morphologically differentiated, have similar or identical
      protein import mechanisms when compared to the chloroplasts in green tissue.

PMID- 15977335
TI  - Beyond biotechnology: FDA regulation of nanomedicine.
AB  - Nanotechnology, which involves investigating and manipulating matter at the
      atomic and molecular levels, may radically transform industry and society.
      Because nanotechnology could introduce whole new classes of materials and
      products, it could present an array of novel challenges to regulatory agencies.
      In this note, John Miller explores the regulatory challenges facing the Food and
      Drug Administration in regulating nanomedical products. First, the FDA will have
      trouble fitting the products into the agency's classification scheme. Second, it
      will be difficult for the FDA to maintain adequate scientific expertise in the
      field. He concludes that the FDA should consider implementing several reforms now
      to ensure that it is adequately prepared to regulate nanomedicine.

PMID- 15977336
TI  - What medicine and the law should do for the physician-assisted suicide debate.

PMID- 15977338
TI  - The ethics of patenting biotechnology.

PMID- 15977337
TI  - Isolation of a prokaryotic photoreceptor: sensory rhodopsin from halobacteria.
AB  - The photoreceptor sensory rhodopsin was isolated from halobacterial cell
      membranes solubilized in laurylmaltoside. In the presence of retinal, detergent
      and salt the native protein was obtained in pure form by sucrose density gradient
      centrifugation, hydroxyapatite chromatography and gel filtration. The apparent
      mol. wt of the molecule was 24 kd if analyzed by SDS gel electrophoresis, and 49
      kd by sedimentation and size-exclusion chromatographic analysis. The
      chromoprotein had an absorption maximum at 580 nm which was 8 nm blue-shifted
      compared to the membrane-bound state. The molecule was photochemically active and
      the action spectrum for formation of SR380, the long-lived intermediate,
      coincided with the absorption spectrum.

PMID- 15977339
TI  - The European Union and stem cell research: a turnaround on policy regarding human
      embryo research?

PMID- 15977340
TI  - Legal, ethical, and social issues in human genome research.
AB  - In the past several decades, biological sciences have been revolutionized by
      their increased understanding of how life works at the molecular level. In what
      ways, and to what extent, will this scientific revolution affect the human
      societies within which the science is situated? The legal, ethical, and social
      implications of research in human genetics have been discussed in depth,
      particularly in the context of the Human Genome Project and, to a lesser extent,
      the proposed Human Genome Diversity Project. Both projects could have significant
      effects on society, the former largely at the level of individuals or families
      and the latter primarily at the level of ethnic groups or nations. These effects
      can be grouped in six broad categories: identity, prediction, history,
      manipulation, ownership and control, and destiny.

PMID- 15977341
TI  - The commodification of the body and its parts.
AB  - The human body--and its parts--has long been a target for commodification within
      myriad cultural settings. A discussion of commodification requires that one
      consider, first, the significance of the body within anthropology and, second,
      what defines a body "part." After exploring these initial questions, this article
      outlines dominant theoretical approaches to commodification within anthropology,
      with Mauss and Marx figuring prominently. The discussion then turns to
      historically well-documented forms of body commodification: These include slavery
      and other oppressive labor practices; female reproduction; and the realms of
      sorcery and endocannibalism. An analysis here uncovers dominant established
      approaches that continue to drive current studies. The remainder of this article
      concerns emergent biotechnologies, whose application in clinical and other
      related scientific arenas marks a paradigmatic shift in anthropological
      understandings of the commodified, fragmented body. The following contexts are
      explored with care: reproductive technologies; organ transplantation; cosmetic
      and transsexual surgeries; genetics and immunology; and, finally, the category of
      the cyborg. The article concludes with suggestions for an integrated theoretical
      vision, advocating greater cross-fertilization of analytical approaches and the
      inclusion of an ethics of body commodification within anthropology.

PMID- 15977342
TI  - The IGF-1--IGFBPs system in the crevicular fluid: its changes during orthodontic
      movement.
AB  - IGF-1 (Insulin-like growth factor-1) is a growth factor whose biological activity
      at cellular level is regulated by 6 binding proteins (IGFBs); one of them, IGFBP
      3, is the most abundant in blood. Both IGF-1 and IGFBP-3 are expressed by bone
      cells and may be important factors in bone remodelling (1-5). The aims of this
      study were to evaluate the presence of IGF-1 and IGFBP-3 in crevicular fluid and
      to assess whether their levels changed during orthodontic tooth movement in
      patients under orthodontic treatment. Orthodontic movement alters alveolar bone
      remodelling. Changes in the amounts of IGF-1 and IGFBP-3 in crevicular fluid may
      reflect changes in alveolar bone remodelling.

PMID- 15977343
TI  - Relation of obesity and of vocational and avocational risk factors to
      osteoarthritis.

PMID- 15977344
TI  - Risk factors for the development and progression of hip osteoarthritis.

PMID- 15977345
TI  - Who gets osteoarthritis and why? An update.

PMID- 15977346
TI  - Mesenchymal stem cell dysregulation in hereditary osteoarthritis.

PMID- 15977347
TI  - How important are genetic factors in osteoarthritis? Contributions from family
      studies.

PMID- 15977348
TI  - From biomarker to surrogate outcome to osteoarthritis--what are the challenges?

PMID- 15977349
TI  - Advances in radiographic imaging of progression of hip and knee osteoarthritis.

PMID- 15977350
TI  - Update on cartilage oligomeric matrix protein as a marker of osteoarthritis.

PMID- 15977351
TI  - Relationship between symptoms and structural change in osteoarthritis: what are
      the important targets for therapy?

PMID- 15977352
TI  - Pain-related beliefs and affective pain responses: implications for ethnic
      disparities in preferences for joint arthroplasty.

PMID- 15977353
TI  - Finding clinical endpoints and biosurrogates in preclinical knee osteoarthritis.

PMID- 15977354
TI  - Why choose hip osteoarthritis as a human model for evaluation of drugs in
      osteoarthritis?

PMID- 15977355
TI  - Increased biological activity of subchondral mineralized tissues underlies the
      progressive deterioration of articular cartilage in osteoarthritis.

PMID- 15977357
TI  - Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in
      children.
AB  - (1) Codeine, either used alone or in combination with paracetamol, is the
      standard step-2 opiate analgesic for children from the age of one year. (2) An
      oral solution of tramadol, another step-2 opiate analgesic, was recently approved
      in France for the treatment of children at least three years of age. (3) The only
      clinical trials of tramadol in this age group focused on short-term treatment of
      postoperative pain. Tramadol has not been compared with codeine, ibuprofen, or
      correctly dosed paracetamol (step-1 analgesic). Tramadol has been compared with
      diclofenac, a nonsteroidal antiinflammatory drug, in a trial that included
      patients over 11 years of age (including adults), but the results of this trial
      are uninformative because patients were not blinded and no separate paediatric
      subgroup analysis was carried out. (4) The adverse effects of tramadol in
      children appear to be mild but frequent (especially vomiting). (5) As with
      codeine, deaths have been reported following accidental overdose with oral
      tramadol in children. (6) There is no justification for prescribing such a
      potentially harmful drug with poorly documented efficacy.

PMID- 15977358
TI  - [Jacques Lisfranc de Saint-Martin (1787-1847)].
AB  - For 22 years Jacques Lisfranc was the famous surgeon at the Hospital La Pitte in
      Paris. He was born at Saint-Paul-en-Jarez in 1787, a village sited between Saint
      Etienne and Lyon. After his Internship in Lyon he became Dupuytren's student in
      Paris. In his thesis, he described Dupuytren's operation of the removal of the
      lower jawbone. In 1815 he succeeded in new surgical operations on the shoulder
      and on the foot. In 1830 he was the first to perform the ablation of rectum's
      carcinoma and became the most famous gynaecological surgeon. He could not become
      a professor of the Faculty of Medicine in Paris because of his enmity with
      Dupuytren. Nevertheless he was only interested in surgery and the care for his
      patients. On his tomb, one can read his favourite maxim: "Surgery is bright when
      operating but it is still brighter when there is no blood and mutilation and yet
      leads to the patient's recovery".

PMID- 15977359
TI  - [Understanding the survey of the Royal Society of Medicine (1774-1793): source,
      problems and methodology].
AB  - The treasures of many archives can be amazing for the historians such as those
      ones of the Royal Society of Medicine which listed all the diseases rife into the
      French provinces since 1774. The listing now appears as weather reports and
      nosology classifications. How to study these reports? What kind of methodology to
      be used?

PMID- 15977360
TI  - What is special about the ethical issues in online research?
AB  - In the analysis of the ethical problems of online research, there is much to be
      learned from the work that has already been done on research ethics in the social
      sciences and the humanities. I discuss the structure of norms in the Norwegian
      ethical guidelines for research in the social sciences with respect to their
      relevance for the ethical issues of Internet research. A four-step procedure for
      the ethical evaluation of research is suggested. I argue that even though, at one
      level, the problems of online research are very similar to those we find in
      traditional areas of scientific research, there still are some issues that are
      unique to research online. A general model for the analysis of privacy and data
      protection is suggested. This model is then used to characterize the special
      problems pertaining to the protection of privacy in online contexts, and to argue
      that one cannot assume a simple distinction between the private and the public
      when researching in such contexts.

PMID- 15977361
TI  - [The reform by Farabeuf of the practical education of anatomy and surgical
      medicine: Ten years street Vauquelin, 1877-1886].
AB  - Louis Hubert Farabeuf overhauled the practical anatomy and surgery education. In
      1876, after the law about the reconstruction of the Faculty of Medicine, he was
      appointed professor of medicine and he let alone the terrible state of the
      practical surgery education in the Progres Medical in Paris. Thus he was
      appointed master of anatomical education in 1878 and his New Practical School of
      Anatomy will become a model for future. Farabeuf proposed the organisation of
      educating buildings, the Anatomical Surgery Education through the treatment of
      corpse and the obligatory dissection for every student. Farabeuf imposed his
      method and hence was the master of the most famous surgeons in the early XXth
      century.

PMID- 15977362
TI  - Research ethics in Internet-enabled research: human subjects issues and
      methodological myopia.
AB  - As Internet resources are used more frequently for research on social and
      psychological behavior, concerns grow about whether characteristics of such
      research affect human subjects protections. Early efforts to address such
      concerns have done more to identify potential problems than to evaluate them or
      to seek solutions, leaving bodies charged with human subjects oversight in a
      quagmire. This article critiques some of these issues in light of the US Code of
      Federal Regulations' policies for the Protection of Human Subjects, and argues
      that some of the issues have no pertinence when examined in the context of common
      methodological approaches that previous commentators failed to consider. By
      separating applicable contexts from those that are not, and by identifying cases
      where subjects' characteristics are irrelevant and/or impossible to provide,
      oversight committees may be able to consider research applications more
      appropriately, and investigators may be less ethically bound to ascertain and
      demonstrate those characteristics.

PMID- 15977363
TI  - [A medico-legal problem of the past: invalidation of the sale of a slave in case
      of concealed disease. Zacchias' opinion].
AB  - In his famous "Questions" Paul Zacchias (1584-1659) deals with the medico-legal
      problem of invalidation of sale of slaves or beasts of burden for concealed
      redhibitory defects. He analyzes the Roman right always used in his time but does
      not show any critical mind while he is only compiling and commenting the texts
      taken from the famous "Edit des Ediles curules". A listing of the redhibitory
      defects is opposed to the slight vices which do not justify the cancellation of
      the sale. What is unknown is whether the judge called for a medical appraisal
      about the reality of the defects, their physical or mental origins, their long
      standing development.

PMID- 15977364
TI  - Abortion and Latter-Day Saint experiences with children and law.

PMID- 15977365
TI  - Private choice versus public health: religion, morality, and childhood
      vaccination law.

PMID- 15977366
TI  - [How Lind did not discover the treatment against the scurvy].
AB  - During 400 years Lind, with his published book "A Treatise of the Scurvy", was
      considered as the man who discovered the role of lemon juice in the treatment of
      scurvy. However lemon juice was given to the English crews only 40 years later
      and more one century later to the French crews. In fact, as Lind had muddled up
      his conclusions of the role of the lemon juice with the supposed role of the
      chillness, dampness and many subsidiary treatments the Admiralty was not
      convinced at once by the necessary lemon juice to prevent the scurvy.

PMID- 15977367
TI  - [The impact of water-regulation on public health in Hungary].

PMID- 15977368
TI  - [History of the discovery of Helicobacter pylori].
AB  - The discovery of Helicobacter pylori is one of the greatest achievements in the
      modern history of gastroenterology, which led to fundamental changes in our
      approach to the pathogenesis and treatment of peptic ulcer disease. However, the
      road towards accepting the role of these spiral bacteria in the pathogenesis of
      certain diseases of the upper digestive tract was long and marked with repeated
      false interpretations and misunderstandings, even when--in retrospect--many times
      several researchers were very near to the discovery. The first observations
      concerning the presence of bacteria in animal/human stomachs dates from the dawn
      of medical microbiology, when the bacterial etiology of some other diseases
      (tuberculosis, cholera, dysentery, syphilis) was ascertained. In spite of many
      bacteriological, experimental, biochemical and therapeutic observations, the
      causative role of the microorganism in the pathogenesis of peptic ulcer was not
      recognised even in the case of most elegant demonstrations. Sometimes, head
      strong thinking and excessive belief in opinion leaders statements set back the
      bacterial research. The identification of Helicobacter pylori by Barry J.
      Marshall and J. Robert Warren in 1983 can not be, in any case, considered as
      serendipitous: without the endeavour, youthful curiosity, talent and ambition of
      the former and solid classical knowledge in pathology of the latter, peptic ulcer
      might be considered even today as an acid-related or psychosomatic disease, as it
      was during the past century.

PMID- 15977369
TI  - Chickenpox vaccines: new drugs. A favourable risk-benefit balance in some
      situations.
AB  - (1) Chickenpox is generally mild. Most severe cases of chickenpox occur in
      immunocompromised patients, adults, and pregnant women (and their foetuses). (2)
      Two live attenuated chickenpox vaccines derived from the same strain of varicella
      virus (Oka) are marketed in France, under the trade names Varilrix and Varivax.
      (3) They have not been adequately evaluated in immunocompromised children. (4)
      The impact of routine vaccination of women of child-bearing age on complications
      of chickenpox during pregnancy has not been studied. (5) Immunogenicity studies
      in several thousand immunocompetent children aged from 1 to 12 years show that
      the vaccine is almost always immunogenic after a single injection. Other
      comparative studies in adolescents and adults show that two injections are
      needed, at least two months apart. (6) A double-blind placebo-controlled trial
      including 513 immunocompetent children showed that Varilrix prevented 88% of
      cases of chickenpox after a median follow-up of 29 months, but no data on severe
      chickenpox were reported. A study that followed up 9202 children aged 1 to 12
      years for more than 13 years showed that vaccination with Varivax failed to
      prevent chickenpox in 12.5% of cases and that 1.7% of these cases were severe.
      (7) Immunocompetent children vaccinated within three days after exposure to the
      virus are partially protected, according to one study of Varilrix (104 children)
      and two small studies of Varivax (10 and 42 children). There are no equivalent
      studies in adults. (8) Local adverse effects such as fever and rash are common in
      immunocompetent vaccinees. The rash is sometimes varicella-like and is due to
      infection by the vaccine strain. Pharmacovigilance studies of Varivax have shown
      no serious adverse effects. (9) Disseminated and/or persistent infection caused
      by the vaccine strain has been reported in immunocompromised patients. (10)
      Vaccination of immunocompetent subjects does not appear to result in a risk of
      chickenpox transmission to subsequent contacts. There seems to be no increase in
      the risk of herpes zoster in vaccinated children nor is there any firm evidence
      that chickenpox vaccination increases the incidence of herpes zoster in the
      general population. (11) Little information is available on vaccination during
      pregnancy. As a precaution, however, pregnant women should not be vaccinated.
      (12) Mass vaccination does not appear to be justified: chickenpox is generally
      mild during childhood, and several questions concerning the effects of the
      vaccine remain unanswered. (13) Chickenpox vaccination should be restricted to
      specific groups of non immune immunocompetent adults who are in a position to
      transmit chickenpox to immunodeficient contacts (e.g. health care personnel and
      kindergarten staff); adults who have been in contact with a case of chickenpox
      within the past three days; and children awaiting transplantation. The potential
      benefits and risks of vaccinating immunocompromised patients should be assessed
      on a case by case basis.

PMID- 15977370
TI  - History of alternative medicine in Hungary in 19th and early 20th century.

PMID- 15977371
TI  - [Function of observation posts and squads escorted wounded transports in the
      Great War].
AB  - In autumn of year 1914 more and more epidemic cases were observed from the
      eastern front-line. The infected wells, the lack of cleanliness and the health
      were the reasons, and the home territory was also in danger because of
      transportation of the wounded soldiers. For the sake of defence the sick soldiers
      were transported as a closed detachment, then "saving zones" were established
      with ill-observation posts. The posts were ruled by two leaders. The commissioner
      of the Minister for Home Affairs prevented spread of contamination, the
      commanding officer of the military squads organized order and subordination.
      There were squads escorted the wounded detachments; they worked in two areas:
      from the border railway stations to the observation posts and at these posts.
      They worked as escorts, supervisors of the sick soldiers. The posts were
      barracks; they consisted of an entrance room, operating rooms, laboratories,
      barracks of infecting and non-infecting ills etc. The soldiers were quartered
      into 5 groups, infecting ills, non-infecting ills, people contacted infecting
      ills, wounded men, other ills. The staff of posts consisted of 57-64 people.

PMID- 15977372
TI  - The struggle of Gustav Schimert for the revival of homeopathy in Hungary (1908
      1944).

PMID- 15977373
TI  - [The possibilities of scientific education through the scientific articles of
      Budapest papers in the second half of the 19th century].
AB  - Enlightenment in health issues has always been a structural part of the generally
      meant healing activities. The ways of addressing the people changed along with
      the centuries: the press was the right medium to inform wide masses of different
      classes of people in the 19th century. The feuilleton was one of the popular
      styles used by the press, nevertheless it grew out of it's classical frames, and
      gained the most various themes during the second half of the century. So the
      feuilletons on natural sciences written by medical doctors about health issues
      appeared as well. These writings represent the natural sciences' knowledge of the
      comfortable and popular sort of positivism and national program spanning from
      Zsigmond Kemeny to Eotvos, where the reader has to feel it's practical use in the
      everyday life. It is the scientific knowledge that is interpreted through these
      feuilletons on the first place, but on the other hand a specific way of reception
      of natural sciences can be traced by them. Their particularity lies at the
      intersection of the most possible subjective description of the objective facts:
      possible historical readings of medical, literary and social sciences. This paper
      tries to catch these moments through the feuilletons of Istvan Apathy, Tihamer
      Balogh and Miklos Dubay.

PMID- 15977374
TI  - [Greek medical science and its understanding of physis, as conceptualized in the
      Hippocratic Treatise De Natura Hominis].
AB  - It has often been claimed the Greek medical science has its origin in the
      rational explanation of the world among the early Greek philosophers that
      constituted their inquiry into nature. However, there were doctors who made an
      attempt to establish medical science as existing independently of any
      philosophical intrusion. This can be elucidated through the analysis of the
      medical term physis, conceptualized, among others, in the well-known treatise in
      the Hippocratic Corpus, entitled De Natura Hominis (NH). In NH, the Hippocratic
      doctor criticizes the philosophical anthropology and medical theory, which hold
      that human nature comes into being emergently from single elemental stuff such as
      Air, Water etc, or from a single humor. His own view of human nature claims that
      the four humors (blood, phlegm, yellow bile and black bile) constitute the nature
      (physis) of human body. The human body has its natural powers inherently for
      preserving health, and, if anything does harm to it, it functions autonomously
      for restoring its normal condition. In this context, the term physis denotes what
      determines the normality of the body, in which its humoral constituents remain
      harmonized with each other. THrough the conception of physis, applied principally
      to the body, the human body will be demarcated as the physical or material aspect
      of human nature, as opposed to the monistic view of human nature, which has not
      drawn a categorical distinction between the material and the non-material.

PMID- 15977375
TI  - Victorian country pharmacy: some gleanings from a prescription book.

PMID- 15977376
TI  - The founder of the Polish and world oil industry: Polish pharmacists Ignacy
      Lukasiewicz and the 150th anniversary of the lighting of the first kerosene lamp.

PMID- 15977377
TI  - Orvietan, a popular and controversial panacea.

PMID- 15977378
TI  - Medical selection and the debate over mass immigration in the new state of Israel
      (1948-1951).
AB  - This paper examines the discourse regarding medical selection of immigrants to
      Israel during the years 1948-51, which was a period of mass immigration in which
      approximately 700,000 people immigrated to the State, thereby doubling the Jewish
      population in only three years. The paper focuses on the debate the preceded the
      Israeli Government's eventual acceptance of a selection policy. We assert that
      the debate was shaped to a large extent by a combination of Zionist ideology and
      eugenic influences - two intellectual forces that had interacted well before the
      creation of the Israeli State in the first half of the 20th century.

PMID- 15977379
TI  - [The interpretation of pulmonary tuberculosis in the 18th century].
AB  - Pulmonary tuberculosis took on alarming proportions in the 18th-century Europe.
      This study examines the ways learned medical practitioners presented the causes
      of the malady in Great Britain and France, by analyzing 12 medical treatises.
      Four etiological models appears to have dominated medical thinking in this
      context: theories that emphasize contagion; those which attribute the cause to
      physiological disorders; those which find the origin in hereditary
      predispositions; and those theories which observe a link with behaviour and
      lifestyles. The study also shows how one of these theories - the hereditary
      theory - eventually triumphed over the others and became the dominant for the
      better part of the 19th century, and will be examined within the context of the
      growth of liberal and individualist ideology.

PMID- 15977380
TI  - "Co-operation in All Human Endeavour": quarantine and immigrant disease vectors
      in the 1918-1919 influenza pandemic in Winnipeg.
AB  - Unlike occurrences of other contagious diseases such as cholera and smallpox, the
      1918-19 influenza pandemic did not lead to anti-immigrant backlash, the
      stigmatization of newcomers as disease carriers, or aggressive quarantine
      measures focused against immigrant groups. During influenza outbreaks in several
      major Canadian cities, quarantine was either rejected or was a low-priority
      containment measure, reluctantly and sceptically employed. Blaming immigrants
      during the epidemic was not considered enlightened public health practice or good
      disease containment strategy. Retrospective evaluation of the successes and
      failures of the fight against influenza concluded that coercive measures such as
      quarantine did more harm than good. The experience with influenza contributed to
      new notions of immigrant inclusion in the social body.

PMID- 15977381
TI  - [Writings of the medical observers on the state of the health of Tunisia under
      the French Protectorate (1881-1956)].
AB  - From the military occupation of Tunisia by France in 1881 to that country's
      independence in 1956, several successive medical observers left behind a wealth
      of information on the state of health of hte populations composing the Tunisian
      mosaic. Even thought pre-colonial Tunisia has often been described as a land
      saddled with disasters and plagues, medical "topographers," most of whom were
      military doctors accompanying the French expeditionary corps, focused on the fact
      that few epidemics ever occurred in Tunisia at the time of the Regency. According
      to some of them, the health situation was better than in Algeria who had been a
      colony for half a century. The research conducted by the Institut Pasteur in
      Tunis and medical dissertations by hospital interns in the Regency's capital
      provide a second source of information comprising invaluable information about
      endemic infectious diseases. In the inter-war period, the social hygiene movement
      concentrated upon fighting tuberculosis and protecting infant and maternal
      health, shifting medical focus to social or "ordinary" diseases and their
      treatment. Prior to Tunisian independence, a third wave of studies conducted by
      the new university's socio-medical research group reinforced the connection
      between lifestyle and health.

PMID- 15977382
TI  - Changes of hippocampus somatostatin and learning ability in rats after +Gz
      exposure.
AB  - OBJECTIVE: To investigate changes of learning ability and somatostatin (SS)
      changes after positive acceleration (+Gz) exposures. METHOD: Eighty male SD rats
      were randomly divided into 3 groups: control group (Con), +6 Gz/3 min group (+6
      Gz), and +10 Gz/3 min group (+10 Gz), 8 rats in each group. Changes of learning
      ability in rats were observed at 0 d, 2 d, 4 d and 6 d after +Gz exposure. SS in
      hippocampus was measured by RIA at 0 d, 2 d and 4 d after +Gz exposures (there
      were 8 rats every time, in each group). RESULT: In Y-maze test, number of correct
      response decreased significantly (P<0.01), and total reaction time increased
      significantly (P<0.01) in +6 Gz and +10 Gz groups as compared with control group;
      number of correct response and total reaction time in +10 Gz group changed
      significantly at 0 d (P<0.01 or P<0.05) as compared with +6 Gz group. RIA showed
      that, content of SS in hippocampus declined at 0 d and 2 d (P<0.05 or P<0.01) in
      +6 Gz and +10 Gz groups as compared with control group. CONCLUSION: +Gz exposure
      could impair learning ability of rats, and inhibit expression of SS in
      hippocampus.

PMID- 15977383
TI  - [Dynamic responses of human body and human surrogate to different impacts under
      30 degrees supine position].
AB  - OBJECTIVE: To study the difference between the dynamic responses of human body
      and human surrogate under 30 degrees supine position, and to discuss impact
      probability of substituting human body with human surrogate in impact tests.
      METHOD: Five volunteers experienced half-sine impact pulses, averaged 4.76, 8.96,
      11.33 G, lasting for 40-60 ms on an impact tower. The human surrogate was exposed
      to half-sine impact pulses, averaged 6.77, 10.39, 16.93, 21.11, 24.98, 31.11 G,
      lasting for 40-60 ms, two times for each G level. ECG changes of the volunteers
      were continuously monitored before, during and after each impact. RESULT: Output
      responses at forehead and chest of human body and human surrogate increased with
      input increments. But there was obvious difference of the dynamic responses
      between human body and the surrogate to impact of low G levels. Heart rate of
      each volunteer had temporary increase during the process of impact, and returned
      to normal level soon after the impact. CONCLUSION: There is difference in a
      certain extend between the dynamic responses of human body and human surrogate.
      The ECG changes are induced mainly by mental stress during process of impact.

PMID- 15977384
TI  - [Effects of nifedipine on myosin heavy chain (MHC) isoforms transition in
      unloaded soleus].
AB  - OBJECTIVE: To observe the effects of nifedipine, a blocker of L-type Ca2+
      channel, on soleus weight and expression of myosin heavy chain (MHC) isoforms in
      control and tail-suspended rats. METHOD: Animals were treated with nifedipine at
      a dose of 10 mg/kg per day in drinking water for 1 or 2 weeks. The expression of
      MHC isoform protein was observed by SDS-polyacrylamide gel electrophoresis at 4
      degrees C. The expression of MHC mRNA was detected by RT-PCR. RESULT: The
      relative weight (muscle weight/body weight) of soleus muscle was decreased by
      39.5% and 51.7% in 1 and 2 weeks of tail-suspended group respectively, but no
      changes in extensor digitorum longus (EDL) weight was found. The relative weight
      of soleus and EDL in 1 or 2 weeks of nifedipine treated control group showed no
      changes as compared with the untreated control group. The relative weight of
      soleus in 1 or 2 weeks of nifedipine treated tail-suspension group decreased by
      36.6% or 52.0%, respectively, as compared with control, but there was no
      difference between tail-suspension group with or without nifedipine treatment.
      The expression of MHC I, IIa mRNA and protein could be detected in control soleus
      with or without nifedipine treatment. The expression MHC I, IIa, IIx and IIb mRNA
      was detected in 1 or 2 weeks of unloaded soleus with or without nifedipine
      treatment. Nifedipine inhibited the expression of II type MHC mRNA in unloaded
      soleus and expression of MHC IIa protein in control and unloaded soleus.
      CONCLUSION: Nifedipine can not resist atrophy of unloaded soleus, but inhibit the
      transition of MHC from slow to fast isoforms at the transcription level.

PMID- 15977385
TI  - [Changes of endogenous ouabain in rat serum and certain tissues after exposure to
      simulated weightlessness].
AB  - OBJECTIVE: To investigate the changes of endogenous ouabain (EO) in rat serum and
      some tissues after exposure to simulated weightlessness and to investigate its
      possible pathophysiology. METHOD: Male Wistar rats were randomly divided into
      control group (Con) and 1 week tail-suspension group (TS). Enzyme-linked
      immunosorbent assay (ELISA) was used to detect the content of EO in serum,
      hypothalamus, pituitary, adrenal gland, kidney, heart and liver. RESULT: Compared
      with Con, EO increased significantly in serum, hypothalamus, adrenal gland and
      kidney after tail suspension (P<0.05). CONCLUSION: Simulated weightlessness
      induced changes of EO in serum and some tissues, which may have some effects on
      the regulation of hydro-electrolyte metabolism and cardiovascular functions.

PMID- 15977386
TI  - [Behavioral changes of rats under rotation stimulation].
AB  - OBJECTIVE: To assess the specification and efficiency of rotation sickness
      indices by monitoring changes of behaviors in rats under rotation stimulation.
      METHOD: SD rats were stimulated by Crampton model with different time courses.
      Pica or kaolin consumption (KC), conditioned taste aversion (CTA) or saccharine
      water ingestion (SWI), 2 h food ingestion (2hFI), and open-field test (OFT)
      scores were observed. RESULT: Apparent changes of the four indices were observed
      after rotation stimulation. SWI, OFT scores and 2hFI decreased exponentially with
      increase of duration of the motion stimulation. KC increased linearly with the
      increase of time within 12 h stimulation. After 18 h stimulation, KC decreased to
      a level even lower than that after 6 or 12 h stimulation. The adjusted
      correlation between changes of the indices and duration of stimulation within 12
      h are: 0.94 for KC, 0.54 for SWI, 0.44 for 2hFI and 0.34 for OFT. The maximum
      efficiency of the four indices appeared at 6-hour stimulation: 70% for KC, 90%
      for SWI, 80% for 2hFI and 95% for OFT. CONCLUSION: It is found that pica and CTA
      were more specific than the other indices. They may serve as primary indices and
      can be combined with the secondary indices such as 2hFI or OFT. Six hours is the
      optimal duration of stimulation by Crampton model for rotation sickness studies.

PMID- 15977387
TI  - [Experimental study on mechanism of recompression therapy of decompression
      sickness].
AB  - OBJECTIVE: To elucidate that recompression is the most efficient measure in
      removing the pathogenic factors. METHOD: When rabbits were suffering from severe
      DCS, their pressure were immediately compressed to 0.5 Mpa. Precordial region was
      monitored continuously with a Doppler flow meter, micrography of the bulbar
      conjunctiva was done intermittently and the behaviors of the animals were
      recorded. RESULT: Effects of therapeutic recompression and elimination of
      circulating bubbles were correlated to rate and extent of recovery of
      microvascular function. The animals' DCS with severe dysfunction or failure of
      blood vessels, DCS became worse owing to progressive impairment of microvascular
      function during recompression and decompression. CONCLUSION: The pressure could
      only cancel the tension provoked by supersaturated gas in the blood so as to
      relieve the spasm of the compensatory blood vessels, which can restore the blood
      circulation and reverse the developing course of the DCS. The pressure, however,
      couldn't recover the function of the blood vessels with severe dysfunction or
      failure, or repair the injured tissues, or eliminate the circulating bubbles
      directly.

PMID- 15977388
TI  - [Changes of EEG frequency-fluctuation characteristics during visual workloads].
AB  - OBJECTIVE: To observe the changes of alpha-band frequency-fluctuation
      characteristics of EEG under visual task. METHOD: Nineteen healthy right-handed
      male volunteers served as subjects, aged 24-32. EEG were recorded during rest
      (eyes-closed and eyes-open) and visual task, then analyzed using EEG frequency
      fluctuation analysis system. RESULT: From eyes-closed to eyes-open, then to
      visual task state, the probability distribution characteristics of alpha-band
      frequency-fluctuation were significantly changed. The probability of 9 Hz and 10
      Hz dominance decreased significantly, while the probability of 8 Hz and 11-13 Hz
      dominance increased significantly. The single component occupying absolute
      dominance was gradually transformed into the competition between these various
      components, and the lower frequency component in the front brain-areas gradually
      occupied dominance; meanwhile, the dominant fluctuation entropy increase
      significantly, the dominant fluctuation energy decreased significantly, and these
      processes showed obviously the brain-area related characteristics. CONCLUSION:
      These changes of alpha-band frequency-fluctuation characteristics reflect the
      further enhancement of brain activities in the areas related to visual task. This
      method may be helpful in the study of visual workloads.

PMID- 15977389
TI  - [Extraction of rabbit somatosensory evoked potentials (SEP) with independent
      component analysis].
AB  - OBJECTIVE: To extract rabbit somatosensory evoked potentials (SEP), by using a
      new technique named independent component analysis. METHOD: The rabbit was
      narcotized and stimulated with 0.5 Hz electric pulse. Potentials at scalp was
      sampled at 3764 Hz. Response signals to repeated stimulations for 3 times mixed
      with background noise was acquired at the same collection point. Independent
      component analysis (ICA) for SEP was established. The mixed signals were
      decomposed by ICA to observe the independent components. RESULT: Independent SEP
      was acquired. CONCLUSION: A time lag of continuous signal source is suitable to
      SEP model. ICA can extract signals of SEP components.

PMID- 15977390
TI  - [Biological effects of space flight on several opportunistic pathogenic bacteria
      and biodestructive fungi].
AB  - OBJECTIVE: To investigate biological effects of space flight on several
      conditional pathogenic bacteria and biodestructive fungi. METHOD: Several
      potentially pathogenic or biodegrading microorganisms, including bacteria,
      actinomyces and fungi, were carried on-board spacecraft for 7 d. Some of the
      biological characteristics were studied by using general microbial test
      technology after recovery. RESULT: In space condition, survival and growth rate
      were promoted, and soluble pigments were produced, while morphological properties
      were changed differently. The antibiotic-sensitivity of certain strains
      decreased, while most of them showed no changes. CONCLUSION: The reproduction
      ability and growth rate of these microorganisms are promoted after being carried
      into space, and morphological differentiation increase. The resistance to
      antibiotics is stable.

PMID- 15977391
TI  - [A study on space mutation of Streptomyces fradiae].
AB  - OBJECTIVE: To study the rule of mutation of Streptomyces fradiae during
      spaceflight, and to select efficient tylosin producing strains for industrial
      production. METHOD: Streptomyces fradiae 9940S(+)-86 were carried on-board
      spaceship "Shenzhou" I, "Shenzhou" III and "Shenzhou" IV sequentially to achieve
      spaceflight mutation breeding experiment. RESULT: After space experiments and the
      screening tests in the lab, 48 strains were obtained which promoted production by
      +20% or more at shaker level. And the highest production of a strain was 14950
      micrograms/ml, which means an increase of 91.5%. CONCLUSION: Comparing the
      results of three tests, it is found that the outer space environment can lead to
      a cumulative mutation. After the medium scale tests and production experiments,
      strain T1-156-84-23 was finally selected to be used for sample production. And
      its output was increased by 18%.

PMID- 15977392
TI  - [Detection of small molecules based on surface plasmon (correction of plasman)
      resonance technology].
AB  - OBJECTIVE: To develop a detective method applied in online assaying of
      astronauts' humours using the portable online bio-molecules analyzer (POBA) based
      on surface plasmon resonance biosensor. METHOD: An assay format was developed
      based on the detection of 2, 4-Dinitrophenyl-hydrazine. The bio-molecule slide
      was made by DNP-BSA. Range of detection and standard curve were obtained using
      inhibition assay. Reliability and specificity of the assay were also tested.
      RESULT: 1) The linear range of the assay was 7.8 ng/ml-2 micrograms/ml with lower
      detection limit of 2.5 ng/ml; 2) Preparation of the bio-molecule slide and
      regeneration of the biosensor ensured detections for many samples. CONCLUSION:
      This assay method can be used to detect small molecules sensitively, rapidly and
      easily. It can be repeated with good reliability, and has a good application in
      space medicine.

PMID- 15977393
TI  - [A simulation study of electrical impedance scan-imaging based on a phantom].
AB  - OBJECTIVE: To testify the feasibility of electrical impedance scanning (EIS)
      imaging and to classify the factors influencing EIS imaging at the early stage of
      electrical impedance scanning breast imaging study. METHOD: Based on the EIS
      experiment workplace, a phantom to simulate the distribution of breast tissue was
      designed. Using NaCl solution and agar block with different conductance, three
      kinds of electric fields disturbances were simulated. RESULT: Different electric
      fields disturbance induced by different conductance distributions bring different
      imaging effects. CONCLUSION: The imaging based on the theory of EIS is feasible.
      Initiative factors influencing EIS imaging are confirmed.

PMID- 15977394
TI  - [A medical ultrasonic image filtering method based on anisotropic diffusion].
AB  - OBJECTIVE: To remove the speckle noise in ultrasonic images by using anisotropic
      diffusion method. METHOD: Based on anisotropic diffusion, a partial differential
      equation, of which the initial data was the input images, was transformed into
      differential forms and solved with iterations. The speckle scale function of the
      equation was modified to make better use in filtering medical ultrasonic images.
      RESULT: By comparing the results with other three filters, the anisotropic
      diffusion method could smooth the speckles very well and the edge of the image
      was also clear. CONCLUSION: Anisotropic diffusion can remove the speckle noise
      effectively and has great potential in filtering medical ultrasonic images.

PMID- 15977395
TI  - [Design of mechanical structure dynamic characteristics and development of
      verification system].
AB  - OBJECTIVE: To present an effective method for structural dynamic characteristics
      design, required design and test means for space products' development. METHOD:
      Computational modal analysis method was used to evaluate natural frequencies and
      modes of the products in the beginning of design, and test modal analysis method
      was used to identify the dynamic parameters of products in the test period.
      RESULT: The proposed computational modal analysis system is capable of making
      static and dynamic analysis, as well as natural frequencies and modes analysis of
      the structure, and this system could be applied in mechanical structure dynamic
      characteristics design. The proposed test modal analysis system could acquire
      real time force and acceleration signals, and obtain the basic modal parameters
      by processing the sampled data. This system could be used to modify mechanical
      products' dynamic characteristics and decrease vibration amplitude. CONCLUSION:
      The computational and test results of two test models demonstrated that the
      developed computational and test modal system is effective. The method can be
      used for design of structural dynamic characteristics of space products.

PMID- 15977396
TI  - [Malfunction simulation by spaceflight training simulator].
AB  - OBJECTIVE: To implement malfunction simulation in spaceflight training simulator.
      METHOD: The principle of malfunction simulation was defined according to
      spacecraft malfunction predict and its countermeasures. The malfunction patterns
      were classified, and malfunction type was confirmed. A malfunction simulation
      model was established, and the malfunction simulation was realized by math
      simulation. RESULT: According to the requirement of astronaut training, a
      spacecraft subsystem malfunction simulation model was established and realized,
      such as environment control and life support, GNC, push, power supply, heat
      control, data management, measure control and communication, structure and so on.
      CONCLUSION: The malfunction simulation function implemented in the spaceflight
      training simulator satisfied the requirements for astronaut training.

PMID- 15977397
TI  - [Changes of somatostatin (SS) in stomach and duodenum of rats after +Gz
      exposure].
AB  - OBJECTIVE: To study effects of +Gz exposure on the change of somatostatin (SS) in
      stomach and duodenum of rats. METHOD: Forty male Wistar rats were randomly
      divided into +1 Gz control group, +5 Gz x 5 min group, +10 Gz x 5 min group and
      repeated exposure [(+5 Gz x 2 min) + (+10 Gz x 2 min) + (+5 Gz x 2 min)] group.
      After +Gz exposure, the rats in each group were anesthesized by aether, and
      gastric and duodenal mucosa were taken immediately. Levels of SS were assayed
      using radioimmunoassay (RIA) methods. RESULTS: Gastric and duodenal mucosa of the
      control group and +5 Gz group were intact and smooth. Under naked eye and light
      microscope, scattered hemorrhagic spoto, small ulcers, submucosal hyperemia, and
      erosion of mucosa were found in gastric antrum and duodenum in +10 Gz group rats.
      Diffuse hyperemia, erosion and small ulcers were found in mucosa of gastric
      fundus, gastric antrum and duodenum of repeated exposure group. Exposure to +Gz
      can increase somatostatin content in gastric antrum and duodenum (P<0.01).
      CONCLUSION: Increase of SS content may play an important role in the prevention
      of pathogenesis of stomach and duodenum after +G exposure.

PMID- 15977398
TI  - [The effect of ribozyme specially cleaving per1 mRNA on c-fos mRNA and its
      expression in hippocampus of morphine addicted mice].
AB  - OBJECTIVE: To study the change of c-fos mRNA and protein in hippocampus of
      morphine addicted mice after injected with ribozyme specially cleaving per1 mRNA.
      METHOD: The recombined plasmid pcDNA 3.1-per1RZ DNA was injected into the
      ventricles of morphine addicted mice to transcript the corresponding ribozyme
      which cleaves per1 mRNA particularly. And then, the brains of mice were fixed by
      perfusion. The level of c-fos mRNA was assayed by in situ hybridization and c-fos
      protein was detected by immunohistochemical staining. RESULT: The level of c-fos
      mRNA and protein decreased after injection of the recombined plasmid pcDNA 3.1
      per1RZ DNA expressing the ribozyme cleaving per1 mRNA. CONCLUSION: The ribozyme
      specially cleaving per1 mRNA has potential function in inhibiting the
      transcription and expression of c-fos and blocking the morphine addiction.

PMID- 15977399
TI  - [ERP correlates of recognition memory for Chinese words].
AB  - OBJECTIVE: To study the ERP old/new effects during a recognition task for Chinese
      words. METHOD: Twenty one healthy right-handed volunteers received a Chinese
      words recognition task. The stimuli were meaningful words consisting of two
      Chinese characters. The EEG signals were recorded from 9 scalp sites of the
      extended 10-20 systems. RESULT: Compared with the new words, the old words
      elicited larger N320 (the frontal old/new effect) at the frontal brain areas and
      larger LPC (the parietal old/new effect) at the parietal brain areas. And the
      peak of LPC appeared significantly earlier in old words ERPs than in new words
      ERPs. CONCLUSION: The old/new effect is significant for the recognition of
      Chinese words, which also consists of the frontal old/new effect and the parietal
      old/new effect. The parietal old/new effect is positive-going, but the frontal
      old/new effect is negative-going. The frontal old/new effect might be affected by
      the language and material.

PMID- 15977400
TI  - The role of angiotensin II in hypertension and end-organ damage.
AB  - Both high blood pressure and the local effects from Ang II contribute to
      cardiovascular morbidity and mortality. From all these effects, it is clear that
      antihypertensive treatment by interfering with the Ang II regulatory system has
      two benefits: It leads to a reduction of blood pressure per se, with the positive
      effects of reducing stress, turbulence and stretch of the vascular wall. It
      decreases Ang II-mediated responses involved in cardiovascular remodelling. The
      recent emergence of several specific Ang II-receptor antagonists such as losartan
      or valsartan has considerably widened the therapeutic options available for the
      treatment of hypertension-related diseases.

PMID- 15977401
TI  - Selective Ang II (AT1) receptor blockade: a rational approach to end-organ
      protection in hypertension.

PMID- 15977402
TI  - Pre-clinical studies on end-organ protective effects from AT1-receptor blockade.

PMID- 15977403
TI  - AT1-receptor blockers and ACE inhibitors: alternatives or partners?

PMID- 15977404
TI  - Living up to expectations? AT1-receptor blockers in clinical trials.

PMID- 15977405
TI  - Multiple imputation procedures allow the rescue of missing data: an application
      to determine serum tumor necrosis factor (TNF) concentration values during the
      treatment of rheumatoid arthritis patients with anti-TNF therapy.
AB  - Longitudinal studies aimed at evaluating patients clinical response to specific
      therapeutic treatments are frequently summarized in incomplete datasets due to
      missing data. Multivariate statistical procedures use only complete cases,
      deleting any case with missing data. MI and MIANALYZE procedures of the SAS
      software perform multiple imputations based on the Markov Chain Monte Carlo
      method to replace each missing value with a plausible value and to evaluate the
      efficiency of such missing data treatment. The objective of this work was to
      compare the evaluation of differences in the increase of serum TNF concentrations
      depending on the -308 TNF promoter genotype of rheumatoid arthritis (RA) patients
      receiving anti-TNF therapy with and without multiple imputations of missing data
      based on mixed models for repeated measures. Our results indicate that the
      relative efficiency of our multiple imputation model is greater than 98% and that
      the related inference was significant (p-value < 0.001). We established that
      under both approaches serum TNF levels in RA patients bearing the G/A -308 TNF
      promoter genotype displayed a significantly (p-value < 0.0001) increased ability
      to produce TNF over time than the G/G patient group, as they received
      successively doses of anti-TNF therapy.

PMID- 15977406
TI  - Simultaneous single unit recording in the mitral cell layer of the rat olfactory
      bulb under nasal and tracheal breathing.
AB  - Odor perception depends on the odorant-evoked changes on Mitral/Tufted cell
      firing pattern within the olfactory bulb (OB). The OB exhibits a significant
      "ongoing" or spontaneous activity in the absence of sensory stimulation. We
      characterized this ongoing activity by simultaneously recording several single
      neurons in the mitral cell layer (MCL) of anesthetized rats and determined the
      extent of synchrony and oscillations under nasal and tracheal breathing. We
      recorded 115 neurons and found no significant differences in the mean firing
      rates between both breathing conditions. Surprisingly, nearly all single units
      exhibited a long refractory period averaging 14.4 ms during nasal respiration
      that was not different under tracheal breathing. We found a small incidence (2%
      of neurons) of gamma band oscillations and a low incidence (8.1%) of correlated
      firing between adjacent MCL cells. During nasal respiration, a significant
      oscillation at the respiratory rate was observed in 12% of cells that disappeared
      during tracheal breathing. Thus, in the absence of odorants, MCL cells exhibit a
      long refractory period, probably reflecting the intrinsic OB network properties.
      Furthermore, in the absence of sensory stimulation, MCL cell discharge does not
      oscillate in the gamma band and the respiratory cycle can modulate the firing of
      these cells.

PMID- 15977407
TI  - New invariants and dimensionless numbers: futile renaissance of old fallacies?
AB  - The necessity of the mathematical description of living processes and the recent
      advances in theoretical syntheses that fit surprisingly well with real data have
      led many scientists to experiment with new "generalizations," beginning with
      allometric equations. I present here, briefly, why caution is needed when
      allometric equations are multiplied or divided to make new ones. This practice is
      flawed by old and recognized problems, such as the fallacy of averages combined
      with misunderstandings that include error propagation, misuse of statistics and
      confounding scale.

PMID- 15977408
TI  - Fertility and life expectancy of the predator Supputius cincticeps (Heteroptera:
      Pentatomidae) exposed to sublethal doses of permethrin.
AB  - The stinkbug Supputius cincticeps (Stal) (Heteroptera: Pentatomidae) can be found
      in agricultural and forest ecosystems feeding primarily on larvae of Coleoptera
      and Lepidoptera, where it can be exposed to insecticide applications. This study
      therefore aimed to evaluate the reproductive potential of S. cincticeps after
      exposition to sublethal doses of permethrin (5.74 x 10(-3), 5.74 x 10(-2), 5.74 x
      10(-1), 5.74 and 57.44 ppb) through the use of a fertility life table. The
      development cycle of this predator was determined in order to calculate its net
      reproductive rate (R0), the infinitesimal (rm) and finite (lambda) rates of
      increase in addition to mean generation time (T). The net reproductive (18.31),
      infinitesimal (rm) (0.050) and finite (lambda) (1.051) rates of increase were
      higher, while generation time (57.93 days) was shorter for S. cincticeps exposed
      to 5.74 x 10(-1) ppb of permethrin than in the control. This indicates a higher
      rate of population increase of this predator when exposed to this permethrin
      dose.

PMID- 15977409
TI  - A radiographic method to estimate lung volume and its use in small mammals.
AB  - In this paper we develop a method to estimate lung volume using chest x-rays of
      small mammals. We applied this method to assess the lung volume of several
      rodents. We showed that a good estimator of the lung volume is: V*L = 0.496 x VRX
      approximately equal to 1/2 x VRX, where VRX is a measurement obtained from the x
      ray that represents the volume of a rectangular box containing the lungs and
      mediastinum organs. The proposed formula may be interpreted as the volume of an
      ellipsoid formed by both lungs joined at their bases. When that relationship was
      used to estimate lung volume, values similar to those expected from allometric
      relationship were found in four rodents. In two others, M. musculus and R.
      norvegicus, lung volume was similar to reported data, although values were lower
      than expected.

PMID- 15977410
TI  - Two alternative models concerning the perialveolar microcirculation in mammalian
      lungs.
AB  - Despite the fact that the concept of sheet-flow in the pulmonary microcirculation
      of mammals was introduced more than three decades ago, the capillary circulatory
      model still prevails in the physiological literature. Since cardiac output is
      identical in the systemic and in pulmonary circulations, it is noteworthy that in
      the former, the resulting arterial pressure is five times higher than that of the
      latter, which means that the corresponding microcirculations must be radically
      different. The present study addresses this problem from both morphological and
      physiological perspectives.

PMID- 15977411
TI  - Isolation, sequencing and phylogenetic analysis of the hemagglutinin,
      neuraminidase and nucleoprotein genes of the Chilean equine influenza virus
      subtypes H7N7 and H3N8.
AB  - We report here on the isolation and sequencing of the hemagglutinin,
      neuraminidase and nucleoprotein genes of the Chilean equine influenza virus
      subtypes H7N7 (A/equi-1/Santiago/77, Sa77) and H3N8 (A/equi-2/Santiago/85, Sa85).
      The sequences obtained allowed a variability analysis, which indicated
      significant differences when compared with other isolates. We found that Chilean
      isolates are more similar to the North American variety than to European
      isolates. Isolate Sa77 is a good candidate for inclusion in a vaccine as it is
      the latest isolate of the subtype H7N7 and is probably better-adapted to the
      equine host. Isolate Sa85, of subtype H3N8, also appears to be a good candidate
      since it has no significant differences in the main antigenic sites with recent
      isolates.

PMID- 15977412
TI  - Production and immune response of recombinant Hsp60 and Hsp70 from the salmon
      pathogen Piscirickettsia salmonis.
AB  - We have isolated and sequenced the genes encoding the heat shock proteins 60
      (Hsp60) and 70 (Hsp70) of the salmon pathogen Piscirickettsia salmonis. The
      sequence analysis revealed the expected two open reading frames that encode
      proteins with calculated molecular weights of 60,060 and 70,400. The proteins
      exhibit a 70-80% homology with other known prokaryotic Hsp60 and Hsp70 sequences.
      The coding regions have been expressed in E. coli as thioredoxin fusion proteins.
      Both recombinant proteins were shown to elicit a humoral response when injected
      intraperitoneally in Atlantic salmon and also conferred protection to fish
      challenged with P. salmonis. The present data will facilitate further studies on
      the involvement of heat shock proteins in protective immunity of fish to
      infection by P. salmonis and their potential use in recombinants vaccines against
      this intracellular pathogen.

PMID- 15977413
TI  - A rapid and efficient method for purifying high quality total RNA from peaches
      (Prunus persica) for functional genomics analyses.
AB  - Prunus persica has been proposed as a genomic model for deciduous trees and the
      Rosaceae family. Optimized protocols for RNA isolation are necessary to further
      advance studies in this model species such that functional genomics analyses may
      be performed. Here we present an optimized protocol to rapidly and efficiently
      purify high quality total RNA from peach fruits (Prunus persica). Isolating high
      quality RNA from fruit tissue is often difficult due to large quantities of
      polysaccharides and polyphenolic compounds that accumulate in this tissue and co
      purify with the RNA. Here we demonstrate that a modified version of the method
      used to isolate RNA from pine trees and the woody plant Cinnamomun tenuipilum is
      ideal for isolating high quality RNA from the fruits of Prunus persica. This RNA
      may be used for many functional genomic based experiments such as RT-PCR and the
      construction of large-insert cDNA libraries.

PMID- 15977414
TI  - IP3 production in the hypersensitive response of lemon seedlings against
      Alternaria alternata involves active protein tyrosine kinases but not a G
      protein.
AB  - IP3 increase and de novo synthesis of scoparone are produced in the
      hypersensitive response (HR) of lemon seedlings against the fungus Alternaria
      alternata. To elucidate whether a G-protein and/or a protein tyrosine kinase
      (PTK) are involved in signal transduction leading to the production of such a
      defensive response, we studied the HR in this plant system after treatment with G
      protein activators alone and PTK inhibitors in the presence of fungal conidia. No
      changes in the level of IP3 were detected in response to the treatment with the G
      protein activators cholera toxin or mastoparan, although the HR was observed in
      response to these compounds as determined by the scoparone synthesis. On the
      contrary, the PTK inhibitors lavendustin A and 2,5-dihidroxy methyl cinnamate
      (DHMC) not only prevented the IP3 changes observed in response to the fungal
      inoculation of lemon seedlings but also blocked the development of the HR. These
      results suggest that the IP3 changes observed in response to A. alternata require
      a PTK activity and are the result of a G-protein independent Phospholipase C
      activity, even though the activation of a G-protein can also lead to the
      development of a HR. Therefore, it appears that more than one signaling pathway
      may be activated for the development of HR in lemon seedlings: one involving a G
      protein and the other involving a PTK-dependent PLC.

PMID- 15977415
TI  - Development of a BALB/c mouse model of Helicobacter pylori infection with fresh
      and frozen bacteria.
AB  - An experimental model for H. pylori infection was established by intragastrically
      challenging BALB/c mice with 1 ml (10(8) CFU/ml) of suspension for two
      consecutive days. Animals were divided into three groups. GA: mice inoculated
      with fresh bacteria; GB: mice inoculated with frozen bacteria, and GC: mice
      inoculated with brucella broth (control group). Animals were killed at 7, 14, 21,
      28, 35 and 60 days pi and fragments of stomach and duodenum were collected,
      paraffin embedded and stained by hematoxylin-eosin and Giemsa. The results showed
      that challenged mice exhibited mild duodenitis and gastritis. In group GA,
      infiltration in the duodenum was lymphoplasmacytic until day 35; in group GB, it
      was lymphomonocytic for 60 days pi. In the stomach, H. pylori induced
      lymphomonocytic infiltration that was present from days 7 to 60 in group GA. In
      group GB, it was only present from days 14 to 35. In conclusion, our data
      suggested that freezing altered pathogenic properties of H. pylori and probably
      inhibited expression of bacterial antigens and consequently the establishment and
      maintenance of infection. Although the animals developed mild duodenitis and
      gastritis, the BALB/c mouse is not susceptible to developing peptic ulcers during
      H. pylori infection.

PMID- 15977416
TI  - Smoking cessation treatment: pharmacogenetic assessment.
AB  - This review focuses on the current status and future directions of
      pharmacogenetics research into responses to treatments for nicotine dependence
      and smoking cessation. Research remains in its infancy and, although the
      potential for individualized treatment tailored to genotype is promising, there
      are practical, ethical and social considerations that must be addressed before
      such research is translated into clinical practice. In particular, future studies
      that need to be conducted before such research is translated into clinical
      practice and potential limitations and barriers to this translation are
      described.

PMID- 15977417
TI  - The pharmacogenetics of asthma: an update.
AB  - Responses to the three major classes of asthma therapy, beta-agonists,
      leukotriene antagonists and inhaled corticosteroids, demonstrate wide inter
      individual variability. Moreover, both asthma and the traits measured in response
      to asthma therapy, including forced expiratory volume at 1 s, are highly
      heritable. This indicates that genetics may play a prominent role in the
      determination of the therapeutic response to asthma. The human genetic
      association trials that investigate responses to each of the three major classes
      of asthma therapy will be summarized, and recent findings in the literature
      highlighted. Altogether, the available data indicate that genetics influences the
      likelihood of an individual responding to a given therapy, indicating that, in
      the future, optimal care for individuals with asthma may include genetic testing.

PMID- 15977418
TI  - Hypertension pharmacogenomics: current status and future directions.
AB  - Hypertension is the most common chronic disease in the Western world, and while
      there are many drug classes from which to choose therapy, only 34% of North
      Americans currently have their blood pressure controlled. The potential clinical
      utility of pharmacogenomics in helping to guide antihypertensive drug therapy
      selection is described. The hypertension pharmacogenetics literature is reviewed,
      which highlights that only a small fraction of the genes that likely contribute
      to antihypertensive response have been studied to date. The genes for alpha
      adducin (diuretic response), the beta1-adrenergic receptor (beta-blocker
      response) and angiotensinogen (response to multiple drug classes) are among the
      genes with the most compelling data (based on replication) as pharmacogenetic
      candidates. Potential limitations of current studies are also discussed. These
      include reliance on clinic blood pressure, which is probably a suboptimal
      response phenotype, and the relatively small sample sizes of most studies to
      date. Also discussed is the relatively simplistic genetic approach that has been
      taken, which has focused largely on a single gene or single nucleotide
      polymorphism within a gene. Multiple ways to overcome these potential limitations
      are described. Hypertension pharmacogenomics holds tremendous potential for
      providing a mechanism by which management of hypertensive patients might be
      improved, and future studies should help move this field towards its clinical
      potential.

PMID- 15977419
TI  - Approaches to the study of inflammatory gene haplotypes and susceptibility to
      cardiac, vascular and pulmonary diseases.
AB  - Haplotype association methods are increasingly being used in the study of complex
      diseases to better understand and correlate genetic polymorphisms with
      cardiovascular and pulmonary disease phenotypes and drug responses. Understanding
      of the human genome is rapidly expanding; how this knowledge is impacting the
      determination of haplotypes and how they can be utilized in the study of complex
      diseases is reviewed. Applied and methodological fields are discussed and
      examples of how haplotypes are used to study complex diseases in this modern era
      are provided.

PMID- 15977420
TI  - Discovery of disease-induced post-translational modifications in cardiac
      contractile proteins.
AB  - Post-translational modifications to myofilament proteins are essential for the
      regulation of cardiac function in both normal and disease states. Recent
      developments in the field of proteomics have produced a variety of useful tools
      to study protein modifications. Current applications of proteomic technologies in
      the study of modifications to myofilament proteins are summarized. The
      separation, identification and characterization of myofilament modifications
      using gel electrophoresis and mass spectrometry approaches are discussed. Each
      method is illustrated and evaluated with selected examples, and several powerful
      emerging technologies are assessed.

PMID- 15977421
TI  - Reverse-phase protein microarrays for tissue-based analysis.
AB  - The deciphering of the human genome has elucidated our biological structural
      design and has generated insights into disease development and pathogenesis. At
      the same time, knowledge of genetic changes during disease processes has
      demonstrated the need to move beyond genomics towards proteomics and a systems
      biology approach to science. Analyzing the proteome comprises more than just a
      numeration of proteins. In fact, it characterizes proteins within cells in the
      context of their functional status and interactions in their physiological micro-
      and macroenvironments. As dysregulated signaling often underpins most human
      diseases, an overarching goal of proteomics is to profile the working state of
      signaling pathways, to develop 'circuit maps' of normal and diseased protein
      networks and identify hyperactive, defective or inoperable transduction pathways.
      Reverse-phase protein microarrays represent a new technology that can generate a
      multiplex readout of dozens of phosphorylated events simultaneously to profile
      the state of a signaling pathway target even after the cell is lyzed and the
      contents denatured.

PMID- 15977422
TI  - Gene expression-driven diagnostics and pharmacogenomics in cancer.
AB  - The advancement of microarray technologies for characterizing tumors at the gene
      expression level has made a significant impact on the field of oncology.
      Profiling gene expression of various human tumors has led to the identification
      of gene expression patterns or signatures related to tumor classification,
      disease outcome and response to therapy. This technology can also be used to
      study the mechanism of action of specific therapeutics. Routine application of
      microarrays in clinical practice will require significant efforts to standardize
      the array manufacturing techniques, assay protocols and analytical methods used
      to interpret the data. Extensive, independent validation using large,
      statistically sound datasets will also be necessary. Studies on gene expression
      profiling of clinically relevant tissue samples with the aim of finding gene
      markers to support disease prognosis and therapy decisions are reviewed.

PMID- 15977423
TI  - Selectivity assessment of kinase inhibitors: strategies and challenges.
AB  - Most small-molecule kinase inhibitors are ATP competitive, which render them more
      likely to cross-inhibit other kinases in the same family or even kinases from
      other families. Assessing compound selectivity is therefore critical for drug
      development. Recent development of several cutting-edge technologies enabled
      rapid advances in kinase selectivity assessment and greatly facilitated the
      industrial drug discovery process.

PMID- 15977424
TI  - Technology evaluation: HspE7 (Stressgen).
AB  - Stressgen is developing HspE7, a recombinant fusion protein comprising the human
      papillomavirus (HPV) E7 antigen and the heat shock protein Hsp65 from
      Mycobacterium bovis, as a potential therapy for conditions associated with HPV
      infection. This therapy is currently undergoing phase III clinical trials.

PMID- 15977425
TI  - Technology evaluation: Chrysalin (Orthologic).
AB  - OrthoLogic (formerly Chrysalis) is developing Chrysalin, a synthetic 23-amino
      acid peptide that mimics a portion of human thrombin. The compound is in phase II
      clinical trials for the potential treatment of diabetic foot ulcers and phase III
      trials for cartilage repair and bone fractures.

PMID- 15977426
TI  - Technology evaluation: alicaforsen (Isis).
AB  - Isis is developing alicaforsen, an RNase H-dependent antisense inhibitor of
      intercellular adhesion molecule-1, for the potential treatment of ulcerative
      colitis. The therapy is currently undergoing phase II clinical trials.

PMID- 15977427
TI  - [Evolution as resistance to entropy. I. Mechanisms of species homeostasis].
AB  - The idea is discussed that the common output of any evolution is creation of the
      entities that are increasingly resistant to further evolution. The moving force
      of evolution is entropy, the tendency to disorder. This general aspiration for
      chaos is a cause of the mortality of organisms and species, however, being
      prerequisite for any movement, it creates (by chance) novelties, which may occur
      (by chance) more resistant to further decay and thus survive. The surviving of
      those who survive is the most general principle of evolution discovered by Darwin
      for particular case of biological evolution. The second law of thermodynamics
      states that our Universe is perishing but its ontology is such that it creates
      resistance to destruction. The evolution is a history of this resistance. Not
      only those who die do not survive but also those who evolve. The entities that
      change (evolve) rapidly disappear rapidly and by this reason they are not
      observed among both the fossils and now-living organisms. We know only about long
      living species. All the existing organisms are endowed with an ability to resist
      other changing. The following main achievements of the species homeostasis are
      discussed: high fidelity of DNA replication and effective mechanisms of DNA
      repair; diploidy; normalizing selection; truncated selection; heterozygote
      superiority; ability to change phenotype adaptively without changing genotype;
      parental care and the K-strategy of reproduction; behavior that provides
      independence of the environment. The global resistance of the living systems to
      entropy is provided the state that all the essential in biology is determined not
      by physical-chemical interactions but could semantic rules. A conception of
      "potential zygotic information" that determines the rules of ontogenesis is
      proposed. A zygote does not contain this information in explicit form. It is
      created de novo step by step during ontogenesis and it could not be decoded
      beforehand. The experimental data on the adaptive mutagenesis and the relevant
      hypothesis are discussed. It is concluded that the special mechanisms for
      speeding-up of evolution as created by evolution are impossible conceptually.

PMID- 15977428
TI  - [Amoeboid properties of cells during early morphogenesis and the nature of a
      possible protozoan ancestor of Metazoa].
AB  - Data analysis reveals that cells of most of the metazoans (especially from the
      phyla Spongia, Placozoa and Cnidaria) at the early stages of morphogenesis
      demonstrateas amoeboid properties i.e. ability to form pseudopodia, to move by
      means of pseudopodia and to phagocyte. In different degress these properties
      could be found at the late stages of embryogenesis and even in adult organisms.
      Moreover, during gastrulation and blastulation blastomeres is able to form
      flagellas and than loose them and return to amoeboid activity. These and other
      facts indicate that both amoeboid and flagellate types of cellular organization
      are programmed in the genome of metazoan cells, as well as their ability for
      mutual transformation. It leads to suggestion that ancestors of Metazoa were
      amoeboflagellates. Anarchic cleavage observed in some invertebrates evidences
      that separated blastomeres is able to aggregate into the unite embryo due to
      cytotaxis. Aggregation of artificially separated cells of sponges, trichoplax and
      cnidaria results in complete recovery of the organism by cytotaxis. Thus, there
      are reasons to suppose that ability of cell aggregation was inherited by the
      Metazoan genome from the amoeboflagellate ancestors. Thus amoeboflagellates may
      be considered as forerunners of Metazoa, i.e. Prometazoa.

PMID- 15977429
TI  - [Mechanisms that limit pollinator range in Ericaceae].
AB  - Studies were conducted in 2001-2003 at Valdai National Park (Novgorod region) and
      at the Zvenigorod biological station of Moscow State University. The morphology
      of flowers, flowering dynamics and composition of insect visiting flowers of
      Ericaceae species: Andromeda polifolia, Chamaedaphne calyculata, Ledum palustre,
      Oxycoccus palustris, Vaccinium myrtillus, V. uliginosum, and V. vitis-idaea L.
      were studied. Some species of insects visiting flowers were excluded from the
      list of pollinators on the basis of observation on their behavior. L. palustre
      was visited mainly by flies where as other investigated species were visited
      mainly by bumblebees. In some cases bumblebees were the only visitors of the
      investigated plants. Mechanisms that protect flowers from flies and short-tongued
      solitary bees visits and ensure a best pollination by bumblebees are various
      among different species of Ericaceae. Efficiency of nectary protection also
      differs among different plant species and is defined by particularities of their
      habitats and flowering phenology. As far as all species of this family during the
      flowering are dominants in typical habitats, a competition for the pollination
      with species of other families in most cases is megligible. Flowering periods of
      V. vitis-idaea and V. myrtillus in forest ecosystems overlapped weakly. Moreover,
      V. myrtillus is pollinated mainly by bumblebee queens where as pollinators of V.
      vitis-idaea are bumblebee workers, solitary bees and horse flies. The other
      investigated plant species inhabit only oligotrophic peat bogs. Thery are
      pollinated by bumblebees but periods of flowering are not overlapped and
      consequently follow one after another. L. palustre and V. uliginosum flower
      simultaneosly but they are pollinated by different pollinators.

PMID- 15977430
TI  - [Life forms of organisms as patterns of organization and spatial ecological
      factors].
AB  - Tectological and archaetectonical approaches which are conventionally used in
      morphology are discussed. The similarity of these approaches to some views on the
      structure and organization of nature systems was shown. These wiews were
      originated within the framework of the modern system-cybernetic conception. The
      morphology particularities of natural object of any rank (from organism to
      biosphere) allow determination of environment influence character. In some cases
      intensity of the influence can be determined. This, morphological-geometrical
      approach of nature investigation acquires high prognostic value. The aspects of
      "pattern organization" concept and its perspectives are discussed. The patterns
      of organization of organisms could be characterized only in the context of their
      interactions with environment. Therefore it is necessary to distinguish new group
      of ecological factors: spatial or chorological one. It was suggested that spatial
      ecological factors is predominant if all other physical factors have no extreme
      values.

PMID- 15977431
TI  - [Light absorption by carotenoid peridinin in zooxanthellae cell and setting down
      of hermatypic coral to depth].
AB  - Carotenoid peridinin absorbs ocean light which could penetrate deep into the
      water. Absolute and relative contents of symbiotic dinoflagellatae zooxanthellae
      are increased with depth of habitat of germatypic corals. To estimate whether the
      presence of peridinin in corals is chromatic adaptation or not, the absorbance of
      solar radiation by different amounts of peridinin and chlorophyll in natice
      zooxanthellae cells was evaluated. Calculations have shown that at the great
      depths the peredinin absorbance corresponds to 42% of total cell absorbance and
      that the increase of light absorbance correlating with changes of its spectral
      characteristics is entirely determined by presence of this carotenoid. The
      increase of amount of peridinin in cell is as much important as important the
      increase of all other pigments taken together. However, at the same time
      selective and preferential accumulation of peridinin and the change of its native
      state in the limits naturally occurred in zooxanthellae cells have only low
      impact on the light absorbance. The presence of peridinin could be considered as
      manifestation of chromatic adaptation of organism. The comparison of light
      absorption by zooxanthellae with different content of peridinin (or without
      peridinin) reveals that this pigment expands the habitat of hermatypic corals in
      ocean waters at 8-17 meters into the deep.

PMID- 15977432
TI  - [An input of heterochronies to the formation of interspecific differences in wood
      mice, Sylvaemus (Rodentia)].
AB  - Difference in adult size and body shape among the closely related species is the
      result of diversification in morphogenetic processes. We examined age variation
      in various external and craniometric characters of four Sylvaemus species from
      Ukrane fauna, S. uralensis, S. arianus, S. sylvaticus, and S. tauricus, using
      cross-sectional techniques. The intensive growth period occurred to be different
      in various species. Rapid growth of S. tauricus continues during all life span,
      while in other species growth rate becomes slower at different stages. This
      peculiarity of S. tauricus may be the result of prolonged and more intensive
      production of somatotropin by adenohypophysis. Side effects of adenohypophysis
      activation are resulted from changes in S. tauricus skull shape and more
      intensive pigmentation in comparison with three other species. Prolongation of
      growth could be developmental mechanism for size increasing in evolution of S.
      tauricus. The independence of body size and pigmentation is principally the same
      at interspecific and intraspecific level.

PMID- 15977433
TI  - Periodontal health of the elderly people in South East local government area in
      Ibadan, Nigeria.
AB  - Health problems involving physical and mental conditions directly or indirectly
      affect the oral health of the elderly. Other ways in which physical and mental
      health conditions influence their health result from the various drug
      prescriptions given for these ailments. Periodontal health is the most affected.
      Various studies have demonstrated that the elderly have the highest rate of
      gingival bleeding, calculus deposits and periodontal pocketing. It is the aim of
      this study to determine the health of the supporting tissues of the teeth using
      periodontal indices such as the C.PI.T.N and mobility index. The study was
      carried out on 690 elderly individuals (403 males and 287 females) who were 65
      years and above living in various wards in the South East Local Government Area
      of Ibadan (S.E.L.G.A). A multistage sampling technique was used to select elderly
      individuals for the study. Two interviewers, 2 record clerks and 2 examiners were
      trained and the examiners were calibrated. The elderly individuals were
      interviewed and examined concurrently. The results highlighted the high
      prevalence of periodontal disease in the elderly in this local government area.
      Only 5.2% were free from periodontal disease. 94.8% had one or another stage of
      periodontal disease. It also demonstrated the poor oral cleanliness among these
      elderly. More than 42% had gross accumulation of calculus. Among the elderly in
      this local government area, 21.6% and 28.8% had shallow and deep pockets,
      respectively whilst 39.3% had one or more mobile teeth. Pockets and excessive
      mobility of the teeth represent advance stages of periodontitis. Majority (70.4%)
      of the elderly in the study claimed they use chewing sticks to maintain oral
      hygiene. The pattern of deposit of calculus along the interdental surfaces, mesio
      and distobuccal surfaces as well as lingual surfaces, question the effectiveness
      of the chewing stick in cleaning these surfaces. This study confirms findings of
      other authors, on oral hygiene in Nigeria. There is an urgent need to establish a
      community based outreach programme to prevent and treat periodontal disease among
      the elderly in this local government area.

PMID- 15977434
TI  - Comparative effects of osmotic and secretory diarrhoea on brush-border
      disaccharide hydrolases in rat.
AB  - The effects of diarrhoea on the activities of brush-border disaccharidases namely
      lactase (EC 3.2.1.23), maltase (EC 3.2.1.20) and sucrase (EC 3.2.1.48) of Sprague
      Dawley strain albino rats were induced in the rats with mannitol while secretory
      diarrhoea was induced with Salmonella typhimurium after an initial treatment with
      streptomycin. The activities of the enzymes were significantly reduced by
      diarrhoea. The extent of reduction in enzyme activity varied in the different
      segment of the small intestine in all the groups. The jejuno-ileal region had
      more changes in enzyme activities than in the duodenum. Higher activity levels
      were observed for maltase than for lactase. In the osmotic diarrhoea model,
      lactase activity was significantly lowered (P < 0.05) in the experimental group
      from day 5 to 10. Maltase activity on the other hand was significantly lowered (P
      < 0.001) at the peak of diarrhoea. Sucrase activity was also lowered
      significantly (P < 0.025) in the experimental animals within the first 10 days of
      diarrhoeal induction. In the secretory diarrhoea model, lactase activity was
      similar in all the experimental groups except for the streptomycin-salmonella
      treated groups and control (P < 0.05). Higher lactase activity levels were
      observed in the secretory diarrhoea model compared to level in the osmotic
      diarrhoea model. Maltase activity levels were also lowered significantly (P <
      0.05) in the experimental animals. Streptomycin had no effect on the activity of
      maltase.

PMID- 15977435
TI  - Outcome of low birth weight neonates in a tertiary health care centre in Lagos,
      Nigeria.
AB  - The records of all low birth weight (LBW) neonates admitted into the Neonatal
      Unit of the Lagos University Teaching Hospital (LUTH) from January 1997 to
      December 2001 were retrospectively analysed in order to determine the outcome and
      risk factors associated with mortality. There were 535 LBW admissions of which
      411(76.8%) survived while 124(23.2%) died. The birth weight specific mortality
      rate for the < 1000g neonates was 818 per 1000, 451 per 1000 for the 1000-1499g,
      216 per 1000 for the 1500-1999g, and 67 per 1000 for the 2000-2499g neonates (X2
      = 127.70, p = 0.0001). Primary indications for admission were neonatal sepsis
      (25.2%), perinatal asphyxia (23.0%) and neonatal jaundice (19.6%) with case
      fatality rates of 20.0%, 34.1% and 10.5% respectively (X2 = 34.24, p = 0.00001).
      Death occurred within 48 hours of admission in 45.2% of subjects and by the 7th
      day, 72.6% had died (X2 = 70.07, p = 0.0001). Significant risk factors associated
      with mortality were birth weight [OR 4.24, 95% CI = 3.14-5.72] and category of
      LBW [OR 2.79, 95% CI = 1.65-4.69]. Sex, twinning, booking status and mode of
      delivery had no significant influence on mortality. Since the provision of
      adequate intensive care for these vulnerable infants remains a major challenge in
      countries with poor resources, efforts should be intensified to implement
      effective strategies for the reduction of low birth weight deliveries.

PMID- 15977436
TI  - Socio-economic determinants of child labour and attitudes to child labour among
      school children in Ibadan.
AB  - This cross sectional study was designed to compare the characteristics of working
      and non-working school children. Two hundred and thirty one working and 236 non
      working children were interviewed. The socio economic factors associated with
      child labour were trading as mother's occupation, father's educational status,
      religion, family type (monogamous vs polygamous) and type of residence. Family
      type (OR = 0.562, 95% C.I. 0.353-0.897, p = 0.016), religion (OR = 0.559, 95%
      C.I. 0.361-0.867, p = 0.009) and trading as mother's occupation (O.R = 2.49, 95%
      CI 1.68-3.68, p = 0.000) were sustained on logistic regression analysis. With
      regard to attitude to child work, 186 (40%) of all respondents thought that
      children should be allowed to work. The majority of those who held this opinion
      150, were child workers. Ten percent of working children had themselves chosen to
      work without any parental influence to do so. Seventy five respondents had ever
      repeated a class. Forty nine of these were working children a prevalence of 21%
      of repeaters compared to 26 non working children, (11%.) p = 0.004. Sixty eight
      percent of children aspiring to careers in artisan trades were child workers.
      Road traffic accidents and poor school performance were the commonest adverse
      effects of child labour indicated by school children. Parents should be educated
      about the adverse effects of child labour on child development. As poverty is one
      of the major root causes of child labour, free and compulsory primary education
      may help to reduce the notion of child work as an option for survival in poor
      families.

PMID- 15977437
TI  - Homogeneous immunoglobulins in Ghanaians living in Accra, Ghana.
AB  - Serum screening for homogeneous immunoglobulins (H-Ig) was done on 149 apparently
      healthy Ghanaians (aged 17-95 years) and 73 sick subjects who presented at the
      Korle-Bu Teaching Hospital from October 1999 to September 2000. Sera were
      screened by agarose gel electrophoresis and those with equivocal results were
      confirmed by immunoelectrophoresis. Immunoglobulin classes (IgG, IgA and IgM) and
      Bence Jones proteinuria were measured and determined by single radial
      immunodiffusion method and heating respectively. Total protein, albumin, calcium,
      uric acid, urea and creatinine were estimated on ACE chemistry autoanalyser. The
      laboratory profile of 5 Ghanaians with a picture of multiple myeloma and one with
      monoclonal gammopathy of undetermined significance drawn from the sick subjects
      (6 of 73) are presented. None of the 149 healthy subjects studied in three age
      groups (17-40; 41-64 and dollar 65 years) had H-Ig, and their serum IgG, IgA,
      IgM, urea, creatinine, uric acid, calcium, total protein and albumin levels were
      within the normal range. H-Ig were present in sera of 6 out of the 73 sick
      subjects (8.2%); 5 of them (4 males, 1 female) presented a picture of multiple
      myeloma. Three of these 5 patients had IgG, and the others IgA paraproteinaemia.
      All 5 patients had immunoparesis which was absent in the 6th patient (a male) who
      also had IgA paraproteinaemia (< 10 g/L), active bone marrow with < 2% mature
      plasma cells and no renal involvement. Results of bone marrow examination
      supported a diagnosis of multiple myeloma in the 3 patients with IgG
      paraproteinaemia, but were not available for the other two. Bence-Jones
      proteinuria was found in 2 (both with IgG paraproteinaemia) of 4 patients (50%)
      available for testing. Renal involvement was indicated in the 5 patients with a
      picture of multiple myeloma as urea and creatinine levels were significantly
      raised.

PMID- 15977438
TI  - Acute phase proteins, trace elements in asymptomatic human immunodeficiency virus
      infection in Nigerians.
AB  - The natural history of Human Immunodeficiency Virus (HIV) infection is
      incompletely understood. Factors other than HIV infection alone may be required
      for the development of the profound immunosuppression that characterizes advanced
      HIV disease. Nutritional status plays an important role in maintaining normal
      immunity and thus may be one of these factors. The plasma concentrations of C
      reactive protein, transferrin, selected trace elements (Mg, Zn, Fe, Cu, Cd, Se
      and Cr,), total protein and albumin were determined in 25 asymptomatic HIV
      infected Nigerian subjects and 30 age matched HIV-seronegative controls using
      single radial immunodiffusion and spectrophotometric methods. The mean values of
      Cu (73.2 + 23.9 microg/dl), Mg (9.83 + 5.5 mg/dl), Fe (126 + 21 microg/L), Cd
      (24.6 + 7.2 microg/L), Se (22.0 + 12.2 microg/dl) and Cr (19.0 + 5.2 microg/L)
      were low in asymptomatic HIV-positive subjects when compared with the controls
      (Cu = 119.3 + 30.8 microg/dl; Mg = 14.5 + 4.6 mg/L; Fe = 155 + 8.8 microg/ dl; Cd
      = 33. 1 + 8.3 microg/L; Se = 30.9 + 8.3 microg/dl; Cr = 32.1 + 7.8 microg/ L).
      The level of Zn was similar in asymptomatic HIV-positive subjects (5.1 + 1.9
      mg/dl) and the controls (4.6 + 1.7mg/dl). The value of albumin in asymptomatic
      HIV-positive subjects (3.43 + 0.7 g/dl) was significantly low when compared with
      the controls (4.04 + 0.52 g/dl). Significant correlation existed between albumin
      and Mg in asymptomatic HIV subjects (r = + 0.758, p < 0.001). The mean value of C
      reactive protein was significantly higher in HIV-infected subjects compared with
      the controls while the level of transferrin in HIV-infected subjects (92.86 +
      26.3 mg/dl) did not show any significant difference when compared with the
      controls (84.36 + 16.9 mg/dl). This study revealed the deficiencies of trace
      elements in asymptomatic HIV infection and therefore suggests dietary
      supplementation of these trace elements in the infected subjects.

PMID- 15977439
TI  - Experimental trypanosomiasis in Yankasa ewes: the body weight response.
AB  - Sleeping sickness (African Trypanosomasis) is an anthropozoonosis transmitted
      primarily by the tsetse fly. It is associated with a host of clinical indices
      ranging from fever, aneamia and anorexia to reproductive failures in man and his
      domestic animals. The main objective of this study is to appraise the
      responsiveness of the body weight as a clinical indicator of sleeping sickness in
      experimentally infected Yankasa ewes. Twelve mature Yankasa sheep (6 infected and
      6 control ewes) were used in this study. Weekly body weights and daily rectal
      temperature were taken while blood samples for haematology were collected twice a
      week from all animals before and after the experimental infection. Undulating
      parasitaemia was observed, two days post infection and was sustained through out
      the study period of about fifty days in all the infected ewes. Decreased body
      weight was found to be very prominent in the infected animals. All the infected
      ewes progressively lost weight during the experiment with a decrease of about
      17.9% of the original weights while the control ewes had increased by 4.2% at the
      end of the study period. The body weight is therefore a very sensitive parameter
      in the surveillance and management of Trypanosome infections especially in
      Yankasa ewes as experimental animal models.

PMID- 15977440
TI  - Predictors of hazardous and harmful alcohol use among Nigerian freshmen.
AB  - Problem drinking among young persons is a concern among contemporary researchers.
      The present study examines the prevalence and the predictors of hazardous and
      harmful alcohol use among a sample of freshmen at the University of Ibadan
      Nigeria. Five hundred and forty freshmen were surveyed, of which 289 used
      alcohol. The effect of eighteen psychosocial variables on Alcohol Use Disorder
      Identification Test (AUDIT) scores was investigated using regression analysis.
      The results showed that, being a male freshman (r = 0.78, p < 0.0005); coming
      from a polygamous home background (r = 0.59, p < 0.01); high levels of parents
      socio-economic status (r = -0.47, p < 0.0005); living with both parents (r = 
      0.24, p < 0.0005); mother working full time outside home (r = 0.39. p < 0.005);
      increasing number of siblings (r = 0.35, p < 0.0005); living in urban cities (r =
      0.38, p < 0.005); belonging to a social club (r = -0.46, p < 0.01); increasing
      religious activities (r = -0.51, p < 0.005); increasing parent child interaction
      (r = 0.72, p < 0.01); and low need for affiliation (r = -0.49, p < 0.0005) were
      found to be associated with hazardous and harmful alcohol use among the freshmen.
      When these eleven variables were entered into a stepwise multiple regression
      analysis to determine their relative predictive power to hazardous and harmful
      alcohol use among the freshmen, three variables; being a male (p < 0.0005);
      polygyny polygamy (p < 0.0053) and low need for affiliation (p < 0.0053) remained
      significant. There is a need to consider psychosocial factors in designing health
      educational programs for students on alcohol consumption.

PMID- 15977441
TI  - Efficacy and safety of enoxaparin, a low molecular weight heparin in the
      prevention of deep vein thrombosis in Nigerian patients after orthopaedic
      surgery.
AB  - The objective was to determine the efficacy and safety of Enoxaparin as an
      antithrombotic agent in orthopaedic patients at risk for thromboembolism. 49
      patients who had lower limb orthopaedic surgery were studied. They received
      subcutaneous Enoxaparin 40mg 12 hours before surgery and subsequently, daily for
      one week. Blood specimens were drawn at 2 and 12 hours after the first injection,
      and 24 hours after the fourth injection for anti Factor Xa assay. Specimens were
      also taken preoperatively, 1st, 5th and 7th post operative days (POD) for
      determination of Packed Cell Volume (PCV), Haemoglobin level, White Blood Cell
      (WBC) and Platelet Counts. The mean pre-treatment, 2, 12 and 24 hours anti Factor
      Xa clotting times were 14.5 +/- 0.8, 36.2 +/- 5.6, 30.6 +/- 9.8 and 25.8 +/- 9.3
      seconds respectively. The changes were significant, P = 8.2 x 10(-12). The 2 and
      24 hours clotting times corresponded to plasma heparin concentration level of
      0.12 - 0.22U/ml read off from prepared Enoxaparin standardisation curve.
      Significant changes were observed in haemoglobin level, PCV, WBC and Platelet
      Counts when preoperative, 1st, 5th and 7th POD mean values were compared by
      Analysis of Variance--P < 0.01 in all cases. The study showed that Enoxaparin 40
      mg daily caused hypocoagulation within prophylactic range of 0.12 - 0.22U/ml of
      heparin in the plasma. Changes in blood counts were within the limits expected
      post surgery.

PMID- 15977442
TI  - Bioequivalence study of three generic formulations of co-trimoxazole tablets in
      human urine.
AB  - Many proprietary and generic formulations of co-trimoxazole tablets commercially
      marketed in Nigeria are mostly from Asian countries. Nigerians buy these products
      because of their cheaper prices but not confident with regards to therapeutic,
      quality, safety, and efficacy. Health professionals usually are cautious about
      drug product selection and substitution during prescription and dispensing. In
      this paper, the bioequivalence study of three multi-sourced (generic) co
      trimoxazole tablets was carried out on the urine of twelve healthy volunteers.
      The reversed-phase high performance liquid chromatography was employed for the
      analysis. Sulphadoxine was used as internal standard. The limits of detection
      were 76.3 ng/mL for trimethoprim, and 61.9 ng/mL for sulphamethoxazole at 0.16
      aufs. The linearity (n = 5) for the calibration curve was of the order, 1.0000
      for trimethoprim and 0.9998 for sulphamethoxazole; percentage recoveries for
      trimethoprim and sulphamethoxazole were 89.4 and 87.9% respectively. The relative
      bioavailabilities of the two generics to the innovator's product were 104.2%
      (trimethoprim) and 106.8% (sulphamethoxazole); 114.8% (trimethoprim) and 111.8%
      (sulphamethoxazole) for a product of reputable pharmaceutical company in Nigeria
      and Indian product respectively. In conclusion, the three generic formulations of
      co-trimoxazole tablets were biologically equivalent. Interchangeability of drugs
      in prescription and dispensing may be recommended in this situation.

PMID- 15977443
TI  - Violence and HIV/AIDS prevention among female out-of-school youths in
      southwestern Nigeria: lessons learnt from interventions targeted at hawkers and
      apprentices.
AB  - Between 1997 and 2003, four studies on hawkers and apprentices in motor parks and
      work shops in south west, Nigeria were carried out to evaluate the effectiveness
      of interventions aimed at preventing HIV infection and gender based violence
      (GBV). The studies were in 3 phases namely baseline survey, intervention and end
      line survey. Interventions consisting of:--development and distribution of
      education materials and training programmes for the police, judiciary,
      instructors, drivers, traders and apprentices/hawkers, including micro-credit
      facilities were implemented in some of the studies. The major lessons learnt were
      that: Young girls working in the informal sector of the Nigerian economy face
      dual risks of HIV infection and GBV and yet they are seldom targets of
      intervention; Many had been victims of GBV and did not seek redress either
      because they accept it is their lot, are afraid of being stigmatized or are put
      off the prolonged legal system; Perpetrators tend to deny their involvement in
      violence; Despite the challenges involved, interventions implemented among female
      apprentices and hawkers, especially those that involve multiple stakeholders,
      made a difference in protecting this group from dual risks of GBV and HIV/AIDS
      infection. We recommend more intervention programmes for this population, and
      regulation of activities in the informal sector of the Nigerian economy.

PMID- 15977444
TI  - Experience of tubal surgery for infertility at the Obafemi Awolowo University
      Teaching Hospital, Ile-Ife, Nigeria.
AB  - The magnitude of fallopian tube disease and their contribution to infertility in
      Nigeria and in Africa are gross among the cohorts of women presenting with
      difficulty in childbearing. The objective of the study is to assess the trend and
      pattern of tubal disease in infertility and pregnancy rate among patients
      undergoing tubal surgery at the Obafemi Awolowo University Teaching Hospital
      Complex. A descriptive retrospective study of all cases of tubal disease in
      infertility who admitted for surgery between January 1st 1993 and December 31st,
      2000 at the Obafemi Awolowo University Teaching Hospital Complex. There were 6144
      infertile women among 29,011 females of reproductive age group attending the
      hospital during the study period giving an overall incidence of infertility of
      21.2%. Among this group, 1352(22%) were due to tubal disease. One hundred and
      twenty five (125) of these patients showed up for surgery and thirteen
      pregnancies were recorded giving an overall pregnancy rate of 10.8%. About one in
      four of these patients had had previous tubal surgery for infertility.
      Salopingolysis had the best pregnancy rate with about 19.3% success. Tubal
      disease is a common cause of infertility in South Western Nigeria and success
      rates following surgery are low. We advocate the establishment of regional
      fertility centres as a cost effective way of improving access to modern assisted
      conception techniques.

PMID- 15977445
TI  - The effect of exogenous zinc ions on the pattern of oxygen consumption of the
      hepatic mitochondria of albino rats.
AB  - The effect of incubation of coupled liver mitochondria on varying concentration
      of zinc ion was determined. A low concentration of 6 microM zinc ion was found to
      inhibit the rate of oxygen consumption of the liver mitochondria significantly [P
      < 0.01]. There was uncoupling of the liver mitochondria when subjected to varying
      incubation periods. There was no change observed in the control experiment. Zinc
      citrate inhibited the rate of oxygen consumption significantly [P < 0.01] when
      compare with the control. The changes observed in the Zn-aspartate were
      insignificant. Zn-EDTA had no inhibitory or stimulatory effect on the rate of
      liver mitochondrial oxygen consumption.

PMID- 15977446
TI  - Combined effect of chloroquine and insulin administration on some biochemical
      parameters in rats placed on high fat and calcium diet.
AB  - Effect of combined administration of Insulin and Chloroquine on fasting blood
      glucose, total protein, creatinine and uric acid concentration were investigated
      in rats placed on diets high in fat and calcium (SP diet). Thirty-six (36) rats
      (grouped into six) were placed on different treatment: Grams A and B were fed
      with NP (normal diet) and SP diet respectively; Group C was placed on NP diet and
      injected intramuscularly with 100 microg insulin per day; Group D was placed on
      SP diet and also injected with 100 microg insulin per day; Group E was placed on
      SP diet and injected with both insulin (100 microg/day) and chloroquine (20mg/Kg
      thrice weekly); Group F was placed on SP diet and injected with chloroquine
      (20mg/Kg) thrice weekly. After 15 weeks of treatment, a significantly reduced
      concentration of glucose was observed in groups injected with insulin and those
      injected with insulin and chloroquine together (compared with the control groups,
      A and B). The serum total protein and uric acid level were however not
      significantly different in all the rats. Serum creatinine was also observed to be
      significantly lowered in the rats treated with insulin. The results of this study
      thus suggest that insulin and chloroquine administration may result in reduced
      blood glucose level (hypoglycemia). It also suggests that insulin and chloroquine
      administration may further effect an improved kidney function.

PMID- 15977447
TI  - Physicochemical equivalence of chloroquine phosphate tablets.
AB  - Seven brands of chloroquine phosphate tablets sourced from different retail
      outlets in the South-West Nigerian market were analysed in order to determine
      their physicochemical equivalence. The assessment parameters included uniformity
      of weight, friability, crushing strength, disintegration and dissolution tests
      and chemical assay of the tablets. All the brands passed the British
      Pharmacopoeia tests for weight uniformity, disintegration time and dissolution
      rate. Two brands, C and E passed the minimum criterion for crushing strength,
      four brands passed the friability test and two brands exceeded the specified
      amount of active drug content for chloroquine tablets. Only one brand C out of
      the seven brands that were analysed passed all the BP quality specifications.
      Hence none of the seven brands analysed could said to be physically and
      chemically equivalent. This study highlights the need for constant market
      monitoring of new products in order to ascertain their quality.

PMID- 15977448
TI  - Hypoglycaemic hemiparesis in a Nigerian alcoholic.
AB  - Alcoholism is rarely reported as a clinical problem in Nigerians. This report is
      of a Nigerian alcoholic who presented with chest infection and alcohol withdrawal
      symptoms and subsequently developed transient hemiparesis which responded to
      correction of hypoglycaemia. Hypoglycaemia should be considered in all alcoholics
      presenting with hemiparesis.

PMID- 15977449
TI  - Prevalence of obesity among type 2 diabetics in Nigeria a case study of patients
      in Ibadan, Oyo State, Nigeria.
AB  - A cross-sectional study of anthropometric parameters (weight and height) and body
      mass index (BMI) of 212 type 2 diabetic patients was conducted in Ibadan, Oyo
      State, South-Western Nigeria between January and March 2002. Pretested
      Interviewer-administered questionnaires were used to obtain information on the
      socio-economic and medical profiles of the patients who had been attending the
      dietetic clinics of a teaching hospital and a state hospital respectively for
      medical treatment and dietary counseling for at least 6 months. The mean (SD) age
      of the patients was 55 (13.7) years. Fifty-seven percent of them were women and
      forty-three percent men. The mean (SD) weights of the male and female patients
      were 67.4 (11.7) kg and 64.1 (4.6) kg respectively. Majority (83%) of the
      patients were either overweight or obese. The female patients were significantly
      more obese than the males (P < 0.001). This study concludes that certain dietary
      measures and regular moderate exercise which could enhance the achievement and
      maintenance of ideal body weight should be given emphasis in the management of
      type 2 diabetic patients.

PMID- 15977450
TI  - Severe proximal myopathy in advanced renal failure. Diagnosis and management.
AB  - Myopathies encountered in uremic patients may have different pathogenetic
      mechanisms and treatment. Secondary hyperparathyroidism may cause uremic myopathy
      responding to specific treatment. This study aimed at presenting a case
      illustrative of the clinical features, diagnosis and management of uremic
      parathyroid myopathy. A 66-year old man with renal failure from membranous
      nephropathy developed sensory signs of uremic neuropathy and progressive painless
      weakness of the pelvic girdle muscles bilaterally. Motor nerve conduction
      velocity was normal, electromyogram was consistent with a myopathic pattern,
      while muscle biopsy showed a pattern of atrophy more consistent with a
      neuropathic pattern. Serological tests for collagen vascular diseases and
      hyperthyroidism were negative, while serum muscle enzymes were not elevated and
      serum phosphate levels were not low. Serum parathyroid hormone level was grossly
      elevated, while serum calcium was mildly elevated in a small fraction of the
      measurements, serum alkaline phosphatase showed a progressive rise and skeletal
      bone survey did not disclose osteopenia or signs of parathyroid bone disease. A
      course of calcitriol failed to improve the myopathy, which responded promptly and
      dramatically to parathyroidectomy. Uremic parathyroid myopathy, which has a
      characteristic clinical picture, must be differentiated from other neuropathic or
      myopathic conditions that require specific treatments. Progressive parathyroid
      myopathy is, by itself, an indication for parathyroidectomy, which is curative in
      this case.

PMID- 15977451
TI  - Drug supply strategies, constraints and prospects in Nigeria.
AB  - The study set out to identify the strategies for public drug supply in Nigeria,
      assess its functionality, and recommend appropriate means to ensure regular
      availability of safe, efficacious, good quality and affordable essential drugs at
      public health facilities. The investigation was carried out at the Directorate of
      Pharmaceutical services, Federal Ministry of Health (F.M.O.H) Abuja and Federal
      Medical Stores, Oshodi, Lagos. Semi-structured interview was conducted with key
      informants at the Department of Food & Drugs, Drug procurement unit and Central
      Medical store using structured questionnaires and direct informants answers. Our
      study shows that public drug supply in Nigeria is governed by a National Drug
      Policy (NDP) which was introduced in 1990 and it is yet to be reviewed after ten
      years. We also identified the Central Medical Store (CMS) system as the current
      public drug supply strategy in Nigeria. Public drug supply is mainly financed by
      governments and this is inadequate to ensure sustained availability of essential
      drugs. The major procurement methods in use are open tender and direct
      procurement. These methods as presently operated suffer from late order
      placement, delay in payment and poor supplier lead-time mainly attributable to
      lateness in payment for previous drug supplies. These have contributed to stock
      out of essential drugs at public health facilities. Major losses due to
      expiration and spoilage are recorded at both central and peripheral storage
      points despite adequacy of storage facilities and personnel. Road transportation
      was the major mode of drug distribution from central to peripheral storage points
      and shortage of vehicle was a key factor affecting drug distribution. There was
      an apparent lack of a functioning drug management information system to
      effectively coordinate public drug supply and there are no definite systems that
      monitor and evaluate staff performance. The CMS strategy currently used for
      public drug supply in Nigeria has not ensured regular availability of essential
      drugs at public health facilities. Our study suggests that this is more of an
      administrative failure. Public drug supply in Nigeria is therefore in need of
      urgent reforms and this could be achieved through the use of an autonomous drug
      supply agency to assure efficiency and sustainability.

PMID- 15977452
TI  - Vitamin D deficiency in the elderly: it is time for urgent preventive
      intervention.

PMID- 15977453
TI  - Falls incidence and factors associated with falling in older, community-dwelling,
      chronic stroke survivors (> 1 year after stroke) and matched controls.
AB  - BACKGROUND AND AIMS: Using data from the Australian Longitudinal Study of Ageing,
      this study aimed at: 1) investigating differences in the incidence of falls
      between chronic Stroke subjects (n = 181) and matched Non-stroke subjects (n =
      181) who were 65 years or older and community dwellers, and 2) establishing
      factors associated with falling within chronic Stroke subjects. METHODS: Subjects
      reporting a history of stroke 12 or more months ago, and age- and gender-matched
      Non-stroke subjects were extracted from the first wave of the Australian
      Longitudinal Study of Ageing database. Falls incidence and factors associated
      with falling were examined. Falls data were collected based on recall of the
      number of falls in the past year, including falls that did not result in injury.
      RESULTS: Significantly more Stroke subjects reported falling in the previous
      twelve months than Non-stroke subjects (36 vs 24%, p < 0.05). When comparing
      Stroke Fallers to Stroke Non-fallers within the Stroke group, Stroke Fallers were
      significantly more likely to report (i) difficulty in stooping or kneeling, (ii)
      getting up in the night to urinate more than once, and (iii) having a greater
      number of Instrumental Activities of Daily Living problems (p < 0.05). Self
      reported difficulty in stooping or kneeling was the most significant factor
      associated with falling in the Stroke group (OR 2.44, 95% CI 1.30-4.58).
      CONCLUSIONS: Falls are a problem for community dwelling older people with chronic
      stroke and are associated with physical function difficulties. Factors identified
      in this and other similar studies should form the basis for targeted falls
      prevention programs in this high falls risk clinical group.

PMID- 15977454
TI  - Lower limb function as predictor of falls and loss of mobility with social
      repercussions one year after discharge among elderly inpatients.
AB  - BACKGROUND AND AIMS: Poor mobility of the lower limbs in community-dwelling
      elderly people is a predictor of functional decline in terms of disability,
      falls, nursing home admission, and death. However, its predictive value has not
      been studied in acute care hospital settings. The aims of this observational,
      prospective study were: 1) to assess the prognostic value of lower limb function;
      and 2) to compare the predictive value of three performance tests in elderly
      inpatients. METHODS: We studied 144 patients aged 70 or older (60 men and 84
      women, mean age 78.7 +/- 5.6 years), admitted consecutively to a general internal
      medicine ward. Before discharge, patients underwent multidimensional assessment,
      including static and dynamic equilibrium and gait, by the Performance-Oriented
      Mobility Assessment (POMA), Short Physical Performance Battery (SPPB), and
      Functional Reach (FR). One-year outcomes were falls, loss of mobility with social
      repercussions (inability to leave home, or need for nursing home care) and death.
      RESULTS: In univariate analysis, poor results on any of the three tests were
      associated with an increased risk of falls, loss of mobility with social
      repercussions, and death. In multivariate analysis, age, two or more falls, and a
      low POMA score were predictive of future falls, whereas dependency in
      instrumental activities of daily living and a low SPPB score were predictive of
      loss of mobility with social repercussions. No multivariate model was superior to
      univariate ones in predicting death. No associations were found between other
      medical or geriatric characteristics and outcomes. CONCLUSIONS: Lower limb
      mobility tests performed in an acute care hospital setting are predictive of
      future falls, inability to leave home, and/or need for nursing home care.

PMID- 15977456
TI  - Failure to treat osteoporosis and the risk of subsequent fractures in elderly
      patients with previous hip fracture: a five-year retrospective study.
AB  - BACKGROUND AND AIMS: Considering the results of cost-effective analyses, the
      National Osteoporosis Foundation recommends osteoporosis treatment for patients
      with previous hip fracture. The aim of this study was to examine the application
      of adequate treatment for osteoporosis among patients who have had a hip
      fracture. We also evaluated the rate of subsequent fractures after five years.
      METHODS: We conducted a retrospective data study, with a follow-up at five years
      after discharge, in a tertiary teaching hospital with orthopedic services and all
      medical specialities. Treatment for osteoporosis and subsequent fracture rates
      were evaluated in 114 patients with hip fracture. Functional status was assessed
      using the Barthel Index (BI). We also evaluated the rate of subsequent fractures
      after five years. RESULTS: Twenty-five patients (22%) had a new fracture at some
      moment during the follow-up. Six percent at discharge and 12% at five years of
      follow-up were receiving adequate treatment for osteoporosis. After five years of
      follow-up, a decline in their BI persisted in 72% of the 43 surviving patients.
      CONCLUSIONS: Few patients were receiving adequate treatment for osteoporosis
      after hip fracture. Their fracture rates and functional decline were important.

PMID- 15977455
TI  - Older patients with distal forearm fracture. A challenge to future fall and
      fracture prevention.
AB  - BACKGROUND AND AIMS: Falls and fractures in older people are a common health
      problem. Patients with distal forearm fracture are at risk of sustaining new
      fractures. The aim of this work was to describe the characteristics of this
      patient group. METHODS: Sixty women and six men, mean age 68 years (50-86), with
      a recent fall-related distal forearm fracture, filled in a questionnaire about
      medical history, previous falls and fractures. Handgrip strength on the non
      fractured side, one-leg standing, walking tests, and test of vibration sensation
      were measured and a video-nystagmoscopy was performed. RESULTS: One-third of the
      subjects had fallen during the last year, and one-third had had previous fall
      related fractures during the last 10 years. Half of the patients took medication
      and were examined for chronic ailments regularly. Handgrip strength, balance and
      walking capacity declined with age and were similar to reference values. In three
      patients, the vibration sensation value was above the threshold value. Fifty
      patients (76%) had nystagmus, but no relationship between fall direction,
      physical performance and nystagmus was found. CONCLUSIONS: Although apparently
      healthy, many patients exhibited risk factors for new falls and fractures. Our
      recommendation is that these patients should be screened for fall and fracture
      risk and be targeted for preventive measures, besides fracture treatment.
      Physical therapists must play a major role in increasing and maintaining general
      physical functions in this patient group.

PMID- 15977457
TI  - Osteoporosis health-related behavior among healthy peri-menopausal and post
      menopausal Israeli Jewish and Arab women.
AB  - BACKGROUND AND AIMS: Health practices such as calcium-rich diet and exercise, are
      associated with the prevention of osteoporosis. Since studies showed that ethnic
      minorities are less involved in preventive practices, the aim of this study was
      to examine patterns and correlates of osteoporosis health-related behavior in
      Israeli-Jewish and Arab women. METHODS: Interviews were conducted with 261 women
      aged 45 and older (70% Jewish). Health behavior included: physical activity,
      smoking, alcohol consumption, use of hormone replacement therapy, screening
      behavior, calcium intake, pharmacological prevention, and help-seeking patterns.
      Correlates included demographic variables, health characteristics (menopausal
      status, family history of osteoporosis), knowledge about osteoporosis, and
      beliefs (susceptibility and worries about developing osteoporosis). RESULTS:
      Compared with Jewish participants, a lower percentage of Arab women engaged in
      physical activity, were on HRT, and had had bone density examinations. Their
      overall calcium intake was significantly lower as well. Levels of knowledge were
      moderate to low for the whole group, but more so among Arab women. Engaging in
      physical activities was associated with being menopausal and with having more
      knowledge among Jewish women, and with having more knowledge and lower rates of
      concern among Arab women. CONCLUSIONS: Expanding knowledge about osteoporosis may
      prove beneficial for increasing participation in preventive behavior in both
      groups. Special attention should be paid to different levels of education and to
      differences in subjects' needs and accessibility to sources of information.

PMID- 15977458
TI  - General characteristics, clinical features and related factors of osteoporosis in
      a group of elderly Turkish men.
AB  - BACKGROUND AND AIMS: Osteoporosis is an important problem for men as well as
      women, but data and trials for male osteoporosis, prevalence, evaluation and
      prognosis are limited. There are insufficient randomized placebo-controlled,
      multicenter trial data. The aim of this study was to determine the frequency of
      osteoporosis in patients admitted to the Division of Geriatric Medicine of
      Hacettepe University, to compare osteoporosis in men and women, and to determine
      risk factors, relations with social and cultural differences, body weight and
      functional status. METHODS: A retrospective study was conducted from February
      2002 through July 2003. Participants were 783 female and 464 male patients aged
      65 years and over. BMD measures were performed using dual-energy X-ray
      absorptiometry at femoral neck and lumbar spine. Data on calcium intake, history
      of fractures, smoking, alcohol habits, other possible risk factors, serum 25OH
      Vitamin D and iPTH levels were obtained. Creatinine clearance was calculated with
      the Cockcroft-Gaut formula. Functional status was evaluated by geriatric
      evaluation scales. RESULTS: 29.5% of cases of osteoporosis were found in males;
      45.9% of male patients had osteoporosis, 36.6% had osteopenia. Risk factors for
      male osteoporosis were evaluated. Men with low body weight (< 57 kg), BMI < 19,
      physically inactive, and poorly educated men were significantly more
      osteoporotic. No relationships between 25OH-Vitamin D, iPTH levels, creatinine
      clearance, quality of life scales or osteoporosis were found. CONCLUSIONS:
      Geriatrists and internists should focus on male as well as female osteoporosis.
      Nutritional support and physical activity should be encouraged. Age over 65 is
      identified as a major risk factor. Every man over 65 years of age should undergo
      BMD testing for osteoporosis screening.

PMID- 15977459
TI  - A short comprehensive assessment to predict outcome of elderly patients after hip
      fracture.
AB  - BACKGROUND AND AIMS: Hip fractures result in significant functional impairment
      and a high rate of institutionalization. The aim of our study was to evaluate in
      patients with a recent hip fracture the contribution of a short (15-min)
      comprehensive assessment to predict the length of stay and the risk of discharge
      to a nursing home. METHODS: Prospective clinical study conducted in a
      rehabilitation ward of the Geriatric Hospital. Functional assessment included
      basic activities of daily living (BADL), cognitive status (MMSE) and a 4-item
      geriatric depression scale (Mini-GDS). Information on demographic data, living
      situation, diagnosis and illness burden was also collected. RESULTS: The mean age
      of the 86 patients (67W/19M) was 84.2 +/- 6.8 years. In a multiple regression
      analysis, the length of stay in a geriatric hospital was significantly associated
      with both marital status (living alone) (p = 0.035) and the intervention of a
      caregiver on a regular basis (p = 0.036), but not with Charlson's comorbidity
      score. In a logistic regression model, adjusted for age, gender, marital status,
      intervention of a caregiver on a regular basis, BADL, Mini-GDS and Charlson's
      comorbidity score, the only independent predictor of nursing home admission was a
      MMSE < 24, which increased by 10.7-fold (2.2-50.9) the risk of being admitted to
      a nursing home (p = 0.003). CONCLUSIONS: A short comprehensive assessment
      completed a few days after a hip fracture is useful in predicting length of stay
      and risk of nursing home admission.

PMID- 15977460
TI  - Vitamin D receptor polymorphisms, bone ultrasound and mineral density in post
      menopausal women.
AB  - BACKGROUND AND AIMS: Bone structure, geometry and mineral content represent
      complex traits with a significant heritable component. However, the specific
      contributing genes have not been unambiguously identified. The aim of the present
      cross-sectional study was to analyse an association between heel ultrasound
      measurements, partly reflecting bone quality, and VDR (Vitamin D receptor) gene
      polymorphisms in post-menopausal women, and to assess whether these associations
      differ from those of bone density or not. METHODS: BUA (broadband ultrasound
      attenuation, dB/MHz) at the right heel and BMD (bone mineral density, g/cm2) at
      the lumbar spine and hip were measured in 114 post-menopausal women of Caucasian
      origin (62.4 +/- 9.8 years). All probands were genotyped for common VDR
      polymorphisms--FokI, BsmI, Apal and TaqI--by restriction analysis of the PCR
      product. RESULTS: ANCOVA revealed significant associations between calcaneal BUA
      adjusted for BMI (body mass index) and YSM (years since menopause), and BsmI,
      Apal and TaqI genotypes in the VDR gene (p < 0.02; p < 0.0003; p < 0.02 ANCOVA,
      respectively). BMI- and YSM-adjusted BMD was significantly associated with Fokl
      genotypes in the VDR gene (p < 0.028 at lumbar spine, p < 0.007 at hip).
      CONCLUSIONS: The present data show that post-menopausal BMD and BUA are
      determined by different polymorphisms within the VDR gene. Non-coding
      polymorphisms in the 3' end of the VDR gene (BsmI, Apal, TaqI) are related to
      heel ultrasound while the FokI polymorphism in exon 2, located at the opposite
      site of the VDR gene, is associated with BMD measurements. Further studies are
      required to determine whether different polymorphic markers within a single gene
      independently determine various components of post-menopausal bone.

PMID- 15977461
TI  - Vitamin D and calcium supplementation prevents severe falls in elderly community
      dwelling women: a pragmatic population-based 3-year intervention study.
AB  - BACKGROUND AND AIMS: We evaluated the effect of two programs for the prevention
      of falls leading to acute hospital admission in a population of elderly community
      dwelling Danish residents. METHODS: This was a factorial, pragmatic, intervention
      study. We included 9605 community-dwelling city residents aged 66+ years. We
      offered a prevention program consisting of a daily supplement of 1000 mg of
      elemental calcium as calcium carbonate and 400 IU (10 microg) of vitamin-D3 to a
      total of 4957 participants. The remaining 5063 participants were offered home
      safety inspection with dietary and health advice, or no intervention. RESULTS:
      The Calcium and Vitamin D program was followed by 50.3% and the Environmental and
      Health Program by 46.4%. According to a multivariate analysis including age,
      marital status and intervention program, female residents who followed the
      Calcium and Vitamin D Program had a 12% risk reduction in severe falls (RR 0.88;
      95% CI 0.79-0.98; p < 0.05; NNT 9). CONCLUSIONS: The present study supports the
      hypothesis that vitamin D and calcium supplementation prevent falls leading to
      acute hospitalization in community-dwelling elderly females in a northern
      European region known to be deficient in vitamin D.

PMID- 15977462
TI  - D-hormone analog alfacalcidol: an update on its role in post-menopausal
      osteoporosis and rheumatoid arthritis management.
AB  - Alfacalcidol (1-alpha-hydroxyvitamin D3) is a non-endogenous analog of vitamin D
      which can bypass the renal and intestinal regulatory mechanisms that control the
      production of calcitriol (1,25-hydroxyvitamin D3, the active form of vitamin D, D
      Hormone). Alfacalcidol may be metabolized into calcitriol with a limited risk of
      hypercalcemia. Alfacalcidol and calcitriol have been evaluated in animal and
      human studies assessing their effects on bone mineral density and fracture rates.
      More recently, they have been shown to produce beneficial effects in muscle,
      immune system, and autoimmune diseases, including rheumatoid arthritis. This
      paper discusses the therapeutic efficacy of alfacalcidol in reports in which it
      has been proposed as an interesting alternative to vitamin D or calcitriol. Some
      recent findings about general metabolism and regulation of vitamin D and its
      analogs are discussed. The biological and clinical effects of alfacalcidol in
      post-menopausal osteoporosis are reviewed, followed by critical appraisal of its
      efficacy in preventing bone loss and falls in the elderly. The last two sections
      discuss the role of D analogs in regulating the immune system, with particular
      regard to rheumatoid arthritis. The main results of this review show that
      alfacalcidol may have a wider range of therapeutic applicability, beyond simply
      restricting it to patients in hemodialysis or peritoneal dialysis with high serum
      levels of intact PTH.

PMID- 15977463
TI  - Treatment preference and tolerability with alendronate once weekly over a 3-month
      period: an Israeli multi-center study.
AB  - BACKGROUND AND AIMS: Osteoporosis is a chronic condition requiring long-term
      treatment, for which compliance is not easy to achieve. 70 mg of alendronate once
      weekly (alendronate OW) provides equivalent efficacy to treatment with 10 mg of
      alendronate once a day (alendronate OD); however, there are relatively few data
      regarding patient and physician preferences for once-weekly vs daily dosing. The
      aim of this study was to measure compliance, convenience, tolerance and relative
      preference of alendronate OW treatment among post-menopausal women with
      osteoporosis and physician satisfaction, compared with previous treatment with
      alendronate OD. METHODS: This open-label, prospective multi-center trial was
      conducted at 14 hospitals and 150 primary-care community clinics in Israel. Post
      menopausal osteoporotic women (n = 3710), who had been treated for at least 1
      month with alendronate OD during the preceding year, were treated with
      alendronate OW for 12 weeks. Convenience, satisfaction, tolerance and relative
      preference of alendronate OW during the trial, compared with past experience with
      alendronate OD, were recorded. RESULTS: Overall, 96% of the patients preferred
      the alendronate OW regimen to the 10-mg daily dosage. Nearly all (98%) the
      patients who completed 12 weeks of treatment, including 77% of patients who had
      previously discontinued daily treatment due to intolerance, were willing to
      continue the alendronate OW regimen. Patient-reported compliance with dosing
      instructions was over 98%. Alendronate OW was well tolerated; only 2.8% of
      patients discontinued, due to adverse events. Physicians were highly satisfied
      with the once-weekly dosing regimen, and recommended continued treatment with
      alendronate OW for 99% of the patients. CONCLUSIONS: The majority of post
      menopausal women with osteoporosis, including those who were previously
      intolerant to alendronate OD, preferred alendronate OW to the once-daily dosing
      regimen. It is important to consider patient preference when selecting the
      appropriate treatment for osteoporosis.

PMID- 15977464
TI  - Vertebral fracture risk reduction with risedronate in post-menopausal women with
      osteoporosis: a meta-analysis of individual patient data.
AB  - BACKGROUND AND AIMS: The effect of risedronate, a potent pyridinyl
      bisphosphonate, on vertebral fractures in post-menopausal women was evaluated in
      randomized, placebo-controlled clinical trials. These trials included two large
      vertebral fracture studies that used time-to-event methods to evaluate the
      effects of treatment on fracture risk, thereby allowing both the occurrence and
      the timing of fractures to be considered. METHODS: We used individual patient
      data (IPD) and time-to-event methods to perform a meta-analysis of the anti
      fracture efficacy of risedronate (2.5 or 5 mg daily) in osteoporotic women
      enrolled in five double-blind, placebo-controlled clinical trials. Women were
      included in the analysis if, at baseline, they had either at least one prevalent
      vertebral fracture or a femoral neck bone mineral density (BMD) T-score of less
      than -2.5, were at least 1 year post-menopausal, and had had vertebral fracture
      assessments (N = 3331). RESULTS: Risedronate 5 mg daily reduced the risk of
      radiographically defined vertebral fracture by 64% (95% CI, 46 to 76%, p < 0.001)
      in the first year of treatment and 45% (95% CI, 31 to 57%, p < 0.001) in 3 years.
      The numbers of patients who needed to be treated with risedronate 5 mg to prevent
      one new vertebral fracture over 1 and 3 years were 21 and 13, respectively.
      Comparable findings were observed in sub-populations defined on the basis of
      either prevalent vertebral fracture without regard to femoral neck BMD, or
      femoral neck BMD without regard to vertebral fracture status. Risedronate
      significantly reduced the incidence of clinical (symptomatic) vertebral fractures
      in the first 6 months of treatment (p < 0.001). CONCLUSIONS: This meta-analysis,
      based upon five trials and using IPD and time-to-event statistical methods,
      provides a more precise estimate of the effect of risedronate in reducing
      vertebral fracture risk in postmenopausal osteoporotic women than a meta-analysis
      using summary statistics from the literature.

PMID- 15977465
TI  - Effect of whole-body vibration exercise on lumbar bone mineral density, bone
      turnover, and chronic back pain in post-menopausal osteoporotic women treated
      with alendronate.
AB  - BACKGROUND AND AIMS: Exercise may enhance the effect of alendronate on bone
      mineral density (BMD) and reduce chronic back pain in elderly women with
      osteoporosis. The aim of this study was to determine whether whole-body vibration
      exercise would enhance the effect of alendronate on lumbar BMD and bone turnover,
      and reduce chronic back pain in postmenopausal women with osteoporosis. METHODS:
      Fifty post-menopausal women with osteoporosis, 55-88 years of age, were randomly
      divided into two groups of 25 patients each: one taking alendronate (5 mg daily,
      ALN) and one taking alendronate plus exercise (ALN+EX). Exercise consisted of
      whole-body vibration using a Galileo machine (Novotec, Pforzheim, Germany), at an
      intensity of 20 Hz, frequency once a week, and duration of exercise 4 minutes.
      The study lasted 12 months. Lumbar BMD was measured by dual energy X-ray
      absorptiometry (Hologic QDR 1500W). Urinary cross-linked N-terminal telopeptides
      of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels were
      measured by enzyme-linked immunosorbent assay and standard laboratory techniques,
      respectively. Chronic back pain was evaluated by face scale score at baseline and
      every 6 months. RESULTS: There were no significant differences in baseline
      characteristics, including age, body mass index, years since menopause, lumbar
      BMD, urinary NTX and serum ALP levels, or face scale score between the two
      groups. The increase in lumbar BMD and the reduction in urinary NTX and serum ALP
      levels were similar in the ALN and ALN+EX groups. However, the reduction in
      chronic back pain was greater in the ALN+EX group than in the ALN group.
      CONCLUSIONS: The results of this study suggest that whole-body vibration exercise
      using a Galileo machine appears to be useful in reducing chronic back pain,
      probably by relaxing the back muscles in post-menopausal osteoporotic women
      treated with alendronate.

PMID- 15977466
TI  - Why are fewer overseas nurses coming to the UK?

PMID- 15977467
TI  - Risk assessment is key to protecting staff.

PMID- 15977468
TI  - Breaking bad news.

PMID- 15977469
TI  - A lifetime in nursing. Interview by Kathy Oxtoby.

PMID- 15977470
TI  - Tackling latex allergies in patients and nursing staff.
AB  - It has been known for some time that the latex contained in some medical
      equipment, such as gloves, can result in an allergic reaction. A new report from
      the National Patient Safety Agency (NPSA) looks into the response from NHS
      organisations to the threat from latex allergies and whether adequate measures
      have been taken to protect health care staff and patients.

PMID- 15977471
TI  - Mumps.

PMID- 15977472
TI  - Fentanyl.

PMID- 15977473
TI  - The elective re-warming of postoperative cardiac patients.
AB  - The elective re-warming of patients immediately after cardiac surgery is a core
      nursing procedure. Various methods can be used to perform the procedure including
      forced air-warming systems and radiant lights. This article discusses the
      evidence regarding the most efficacious method.

PMID- 15977474
TI  - A systematic approach to the improvement of patient care.

PMID- 15977475
TI  - Diagnosis and management options of ankle sprain injury.
AB  - Ankle sprain is a common injury that accounts for a significant proportion of
      attendances at A&E. This article describes the anatomy and physiology of the
      ankle and discusses options for the diagnosis and management of ankle sprain
      injuries using a case study approach.

PMID- 15977476
TI  - Leg ulcer assessment techniques in a remote rural area.
AB  - Community-based leg ulcer clinics are a cost-effective and efficient way of
      managing patients with leg ulcers in the community (Blair et al, 1988; Moffatt
      and Oldroyd, 1994). According to the Scottish Clinical Standards for Vascular
      Services (NHS Quality Improvement Scotland, 2003): 'It is essential that all
      vascular patients are seen by a nurse with vascular expertise, who is able to
      provide information, support and health promotion advice'.

PMID- 15977477
TI  - The National Lymphoedema Framework Project.
AB  - The National Lymphoedema Framework Project originated from an epidemiology study
      (Moffatt et al, 2003) carried out in South West London, which identified that
      lymphoedema is a significant but unrecognised problem. Lymphoedema is a chronic
      swelling arising from the accumulation of protein-rich fluid that would otherwise
      drain via the lymphatic system. It can be grossly disfiguring, and is associated
      with cancer and its treatment, particularly breast cancer, but it can occur for
      other reasons, such as trauma or parasitic infection, or it may be primary in
      origin (Fig 1). The main aim of the project is to provide sufficient evidence to
      persuade policy-makers that lymphoedema is a major problem that is currently
      under-resourced and for which national guidance for management is required.

PMID- 15977478
TI  - Understanding wound dressings: foam dressings.
AB  - Foam dressings vary in composition and levels of absorbency. They are available
      in both adhesive and non-adhesive options and in a wide variety of sizes and
      shapes (Boxes 1 and 2). Some products have film backings that are waterproof.

PMID- 15977479
TI  - Risk assessment of skin in rheumatic disease.
AB  - Patients with a rheumatic disease are considered to be at high risk of developing
      skin problems because of their restricted mobility, vascular complications and
      the type of medication they are taking.

PMID- 15977480
TI  - Learning how to manage and lead.

PMID- 15977481
TI  - An opportunity to shape patient care.

PMID- 15977482
TI  - The changing face of public service.

PMID- 15977483
TI  - Back to the blame game.

PMID- 15977484
TI  - It's trusts that need to change.

PMID- 15977485
TI  - Closing the poverty trap between study and work.

PMID- 15977486
TI  - We're setting the world to rights.
AB  - Six nurses from two different generations had a round-table discussion to examine
      the profession's shortcomings: from poor leadership to lack of communication with
      patients.

PMID- 15977487
TI  - Mind over matter.

PMID- 15977488
TI  - Football fever.

PMID- 15977489
TI  - Assessment of the side effects of antipsychotic medication.
AB  - BACKGROUND: Antipsychotic medication is the first-line treatment for people with
      psychosis in the State Hospital, Carstairs: Scotland's only high-security
      forensic hospital. The Clinical Standards for Schizophrenia (Clinical Standards
      Board for Scotland 2001) require clinicians to use standardised rating scales to
      monitor the side effects associated with medication. Liverpool University
      Neuroleptic Side Effect Rating Scale (LUNSERS) (Day et al 1995) was implemented
      in the hospital in December 2003. A baseline audit was carried out following its
      implementation to establish the incidence of side effects. Of those patients
      audited (n=152), 87 (57 per cent) reported either low or medium (n=51, 34 per
      cent) LUNSERS scores, indicating an acceptable level of medication tolerance.
      CONCLUSION: It is expected that clinicians will continue to use LUNSERS as part
      of their routine clinical practice to help inform patients and meet national
      standards.

PMID- 15977490
TI  - Evidence-based practice: compatibility with nursing.
AB  - This article explores the compatibility of evidence-based practice with nursing.
      The generation of relevant research evidence in nursing and determining best
      evidence are discussed. The article concludes that different forms of research,
      other than randomised controlled trials, are valid and in many cases more
      applicable to nursing practice, and that nurses need to determine what
      constitutes relevant and best evidence for the profession.

PMID- 15977492
TI  - Obesity in childhood.

PMID- 15977491
TI  - Peritoneal dialysis.
AB  - Peritoneal dialysis has much to offer patients with chronic renal failure who
      wish to manage their care and live relatively independent lives. The authors
      discuss different peritoneal dialysis treatments, patient selection, benefits and
      the management of potential complications.

PMID- 15977493
TI  - Electronic nursing.

PMID- 15977494
TI  - We are all responsible.

PMID- 15977496
TI  - [Health, uniformity and equity].

PMID- 15977495
TI  - Prescription drugs: uses and effects. Antidepressants: mental illness.

PMID- 15977497
TI  - [Extrahepatic manifestations of chronic liver diseases].
AB  - Chronic liver diseases are commonly associated with extrahepatic disease
      manifestations. Liver cirrhosis, the end stage of chronic liver diseases of
      different etiologies, can result in severe neurological, renal and pulmonary
      complications. Hepatic encephalopathy plays an important socio-economic role,
      since it affects daily functioning and fitness to drive. During the clinical
      course of chronic viral hepatitis, many patients develop extrahepatic disease
      manifestations, which lead to significant morbidity and mortality. In particular,
      mixed cryoglobulinemia, membranoproliferative glomerulonephritis and
      polyarteriitis nodosa are strongly associated with chronic viral hepatitis. Most
      extrahepatic manifestations are due to immunological and lymphoproliferative
      pathomechanisms. Knowledge of extrahepatic disease manifestations is important
      for adequate medical care and risk assessment of patients with chronic liver
      diseases by insurance companies.

PMID- 15977498
TI  - [Indications for the surgical therapy of obesity with magenband operation
      (gastric banding)].
AB  - Morbid obesity is an increasing problem in most of the industrial countries.
      Conservative treatment strategies are often not very effective. Because of the
      enormous costs and concomitant diseases of obesity, effective therapeutic
      strategies are mandatory. Gastric banding is a surgical method to reduce weight
      in the long run when patients are morbidly obese. A silicone band is used to
      create a small pouch in the upper part of the stomach leading to early satiety
      after ingestion only small amounts of food. The benefit of this method is the
      laparoscopic technique and the reversibility, because the band is easy to remove.
      In the long run a significant reduction of weight and an amelioration or even
      prevention of diseases resulting from obesity can be achieved. To assure
      treatment quality, it makes sense to administer this therapy in an
      interdisciplinary setting that integrates psychosomatic diagnostics and
      therapies, too. This paper reviews indications, contraindications as well as pre-
      and postoperative necessarily care of gastric banding.

PMID- 15977499
TI  - [The quality of medical experts' reports].
AB  - Medical experts' reports make a considerable contribution towards decision-making
      both for the social insurance system and for the private health insurance
      industry. Only high-quality expert statements from persons who are also familiar
      with the legal conditions of the commissioning parties in each case can do
      justice to such a responsibility. Hitherto there have been only rudimentary
      approaches to evaluating the quality of medical experts' reports in a
      standardised manner, although shortcomings in this sector are being increasingly
      reported. The following article aims to convey the basic requirements for quality
      assured service-provision and presents the fundamentals of quality assurance for
      a medical service-provision.

PMID- 15977500
TI  - [Medical assessment].
AB  - Multimorbidity and comorbidity in insured persons require a single medical
      assessment. The key aspects of such an assessment are the ability to view insured
      persons holistically, a functional interpretation of structural organ disorders,
      and test results. The performance of a medical report (form and content) is a
      further important quality factor.

PMID- 15977501
TI  - [Attention deficit-hyperactivity disorder and ergotherapy].

PMID- 15977502
TI  - [Motor disabilities after skull-brain trauma].

PMID- 15977503
TI  - [Scientific verification is also required for complementary medicine methods].

PMID- 15977504
TI  - [Wellness check-up for 4300 euros].

PMID- 15977505
TI  - Looking after yourself.

PMID- 15977506
TI  - Whose line is it anyway? Management of central venous catheters in children.

PMID- 15977507
TI  - Holding children for invasive procedures: preparing student nurses.

PMID- 15977508
TI  - Linking theory and practice in children's nursing: lessons from abroad.

PMID- 15977509
TI  - Baby massage and baby play: promoting touch and stimulation in early childhood.

PMID- 15977511
TI  - Privacy: what does it mean for children's nurses?
AB  - Children and young people have a right to privacy and respect. However, conflict
      can arise, particularly in relation to family life, which cannot be side-stepped
      by nurses. This article gives an overview of the legal and ethical rights of
      children and young people.

PMID- 15977510
TI  - Disability and sexuality: holistic care for adolescents.

PMID- 15977512
TI  - Advances in the management of myeloma.

PMID- 15977513
TI  - The Scottish Intercollegiate Guidelines Network (SIGN): an update.

PMID- 15977514
TI  - Non-attendance at secondary prevention clinics: the effect on lipid management.
AB  - BACKGROUND: Secondary prevention of coronary artery disease is effective in
      reducing morbitiy and mortality. Our aim was to assess lipid management following
      non-attendance to a hospital based secondary prevention clinic. METHODS: Data
      were collected over 5 years on statin usage and total cholesterol levels for
      patients with coronary artery disease following attendance at a cardiac nurse led
      outpatient clinic. Lipid levels were taken from a central laboratory database,
      for both patients discharged from clinic and non-attenders. RESULTS: From 935
      inpatients discharged from hospital, 248 (29%) defaulted from outpatient follow
      up. Lipid lowering drug usage was similar (72% vs. 74% for non-attenders, p=NS).
      Attenders at the nurse led outpatient clinic were more likely to achieve a total
      cholesterol <5 mmol/L at discharge than non-attenders (70% vs. 43%; p < 0.001),
      with a lower mean total cholesterol (4.75 +/- 0.06 mmol/L vs. 5.33 +/- 0.08
      mmol/L; p < 0.001). Non-attenders subsequently had a greater number of
      cholesterol measurements than those who were discharged from the hospital based
      clinic (range 0-12, c2 23.8 on 12 df p < 0.005). Lipid profiles in hospital non
      attenders remained inferior with fewer achieving a total cholesterol <5 mmol/L
      (61% vs. 78%; p < 0.001), and having greater mean total cholesterol levels (4.85
      +/- 0.06 mmol/L vs. 4.52 +/- 0.05 mmol/L; p < 0.001). CONCLUSIONS: Patients
      defaulting from hospital follow up have higher total cholesterols with fewer at
      target level compared to attenders. Though non-attenders receive subsequent lipid
      measurement, inferior lipid profiles persist compared to patients who completed
      hospital follow up to be discharged. Further implementation strategies are needed
      with regard to lipid management in this patient group.

PMID- 15977515
TI  - Is 'clicky hip' a risk factor in developmental dysplasia of the hip?
AB  - BACKGROUND: The role of the 'clicky hip' symptom as a prognostic predictor of
      developmental dysplasia of hip (DDH) is controversial. We aim to study the role
      of isolated hip clicks as a prognostic predictor of DDH. MATERIAL AND METHODS:
      235 babies with persisting or referred with clicky hip beyond six weeks of age
      were prospectively followed up to note the incidence of DDH. Of these 176 babies
      were referred for a hip click without additional risk factors. RESULTS: 7 out of
      176 cases (4-IIa, 2-IIb, 1-IIc) had initial abnormal ultrasound examination based
      on Graf classification. However, all babies with isolated hip clicks eventually
      had normal hips on clinical and radiographic examination. DISCUSSION: While
      screening of babies with clicky hips does help in diagnosing the odd case of DDH
      this is not. consistently reproducible. Modifying the targeted ultrasound
      screening by including clicky hip as a risk factor will not reduce the incidence
      of missed cases. Isolated clicks in the hip joint beyond six weeks age are rarely
      a predictor of DDH. However when in doubt such cases should be referred to be
      reviewed by an orthopaedic surgeon or a radiologist experienced in hip
      ultrasound.

PMID- 15977517
TI  - Computerised audit system in urology.

PMID- 15977516
TI  - Weight changes after vertical banded gastroplication.
AB  - AIMS: This study assessed the patterns of weight change in response to surgical
      treatment for obesity. METHODS: Vertical Banded Gastroplication (VBG) was
      performed during the period 1994-2000. Patients were required to follow a liquid
      diet (800 kcals)for 12 weeks before surgery. The same diet plus a multivitamin
      capsule (Forceval) was followed for 12 weeks postoperatively, after which normal
      foods were introduced. Data from 23 patients, 16 women and 7 men, aged 33-63
      years (mean, SD; 42 +/- 8 yrs), with BMI from 38 to 69 kg/m2 (52.5 +/- 8.1 kg/m2)
      at the time of the surgery were available for analysis. Follow up was 3 to 7
      years (mean 4 years). RESULTS: An initial weight loss of 44.4 +/- 24.3 kg (min
      11.5, max 110.5 kg) was reached during the first two years (mean BMI decrease
      15.8 kg/m2). However a regain in weight (36% of the initial weight loss = 5.6
      kg/m2) up to 3 to 7 years after surgery was usual. Average annual regain was 13.6
      kg (n=17), 9.45 kg (n=11) and 0.8 kg (n=8) during the 3rd, 4th and 5th year after
      surgery). Five participants reached a BMI below 30 but only one, BMI < 25, has
      maintained all the weight loss after 5years. CONCLUSIONS: Weight lossfollowing
      VBG ceased after twoyears with a subsequent substantial weight regain. Auxiliary
      therapies to counteract weight regain are necessary after VBG.

PMID- 15977518
TI  - What happens when GPs proactively prescribe NRT patches in a disadvantaged
      community.
AB  - BACKGROUND AND AIMS: The high prevalence of smoking in disadvantaged communities
      gives serious cause for concern in terms of adverse effects on health and social
      outcomes. In Scotland, smoking -related lung cancer rates are particularly high
      and compare less favourably with the rest of the U.K. and Europe. GPs are
      increasingly being recognised as having an important role in smoking cessation
      and are allowed to prescribe NRT to those on a low income. This study aimed to
      follow up a group patientsfrom a disadvantaged area who had been prescribed
      nicotine patches by their GP. METHODS: An initial self-complete questionnaire
      gathered details on age, sex, motivation, marital status, employment history,
      contact with other smokers, concern about weight gain, and nicotine dependence.
      (Nicotine dependence was assessed by using the Fagerstrom Test). Follow up was
      carried out at three months after commencing NRT prescription. Data was also
      gathered from patient case notes as to whether the participant had a smoking
      related diagnosis, periods of depression, drug and/or alcohol problems. Outcome
      was measured in terms of "smoke the same", "smoke less" and "stopped". The
      statistical methods used for testing each factor against smoking were Spearman
      rank correlation, chi-squared test for trend and Kruskal-Wallis test. Basic
      descriptive statistics were used to report general outcomes of the study.
      RESULTS: The study enrolled 120 patients but 19 were lost to follow up. Out of
      101 who used their prescription, 35 were smoking the same, 46 were smoking less
      and 20 had stopped. The variables most strongly affecting outcome were age, with
      older smokers having more success (p < 0.001), and those who had a diagnosis of
      depression having a worse outcome in terms of smoking cessation (p < 0.05).
      CONCLUSION: This study's findings indicate that encouraging GPs to take a
      proactive approach in prescribing NRT is effective, even in an area of socio
      economic deprivation, and particularly with older smokers.

PMID- 15977519
TI  - Timing of aspirin and secondary preventative therapies in acute stroke: support
      for use of stroke units.
AB  - BACKGROUND: We aimed to study the timing of aspirin prescription in ischaemic
      stroke comparing patients admitted to an acute stroke unit (ASU) directly or via
      a general medical ward. We also analysed prescription of secondary preventive
      therapies in stroke patients in an ASU. METHODS: Retrospective analysis was made
      of medical notes and prescription records of 69 patients admitted to an ASU over
      a three month period to establish timing of aspirin prescription with respect to
      onset of stroke symptoms, CT brain scan and route of admission to the ASU.
      RESULTS: CT brain scans were obtained at a median of 2.1 days post stroke (IQ
      range 1.3-4.3). Patients directly admitted to the ASU received aspirin earlier
      post admission compared to those admitted via a medical ward (0.7 vs 2.2 days, p
      < 0.01) and were also more likely to receive aspirin prior to CT scan being
      performed (57% vs 19%, p = 0.02). 86% of stroke patients were discharged on an
      antiplatelet therapy, 79% on a statin, 37% on a thiazide diuretic and 32% on an
      ACE inhibitor or angiotensin II antagonist. CONCLUSION: Aspirin was given more
      promptly in acute stroke and more commonly prior to CT scanning in an ASU
      compared to a medical ward. Statin therapy is used extensively in stroke but
      there is a much lower rate of initiation of other secondary preventive therapies
      (e.g. anti-hypertensive therapy) in hospital. These findings demonstrate a
      hesitancy in early use of aspirin amongst general physicians and lends support
      for the use of stroke units.

PMID- 15977520
TI  - Psychiatric characteristics of frequent attenders at accident and emergency: a
      case register comparison with non frequent attenders.
AB  - BACKGROUND AND AIMS: Patients attending Accident and Emergency (A&E) on a
      frequent basis consume a large amount of NHS resources and often frustrate health
      workers employed in the service. This audit aimed to identify the personal and
      psychiatric characteristics of these patients and highlight areas where
      intervention may be helpful. METHODS AND RESULTS: Patients presenting to A &E
      more than 20 times in four years were comparison to non-frequent attenders using
      case register information. The study demonstrates that frequent attenders are
      well known to psychiatric services, but are not engaged in ongoing contact. This
      is not due to a difference in attendance rate between frequent attenders and
      controls but may represent reluctance for follow up either on the part of the
      patient or the psychiatrist. CONCLUSIONS: These patients have a combination of
      physical, psychiatric and social pathologies and the services to address these
      needs does not seem to currently exist but should be considered.

PMID- 15977521
TI  - Does a hospital formulary influence prescribing practice in an acute medical
      admissions unit?
AB  - AIM: To assess the extent to which prescribing of cardiovascular medications in a
      busy medical unit deviates from the local joint primary and secondary care drug
      formulary guidelines. METHOD: A retrospective audit of the case notes,
      prescription charts and discharge summaries of 150 randomly selected emergency
      medical admissions over a 4 month period. RESULTS: No patient receiving a non
      formulary cardiovascular drug on admission had the choice reviewed in line with
      formulary recommendations. One third of new cardiovascular medications commenced
      in hospital were not compliant with formulary recommendations. Decisions about
      drug therapy were rarely justfied in the written hospital record. CONCLUSIONS:
      Our results demonstrate that in a busy acute medical admissions' unit there is a
      clear failure to amend or query non-formulary prescribing at the time of
      admission and a tendency to exacerbate it during the inpatient period. This
      potentially undermines the purpose of a joint drug formulary as a guideline for
      safe, evidence-based and cost-effective prescribing.

PMID- 15977522
TI  - Niemann-pick disease type C and Crohn's disease.
AB  - A five-year-old girl with Neimann-Pick disease type C subsequently developed
      Crohn's Disease. This association has only been presented once previously in the
      literature. This report discusses the options for managing one chronic disease in
      the presence of another life limiting condition.

PMID- 15977523
TI  - Adrenal pseudocyst--diagnostic dilemma.

PMID- 15977524
TI  - [Patient-nurse or client-vendor?].

PMID- 15977526
TI  - [Markers for the immeasurable].

PMID- 15977525
TI  - [Hesitant nursing personnel].

PMID- 15977527
TI  - [Chaos, so that one can see the stars dance again].

PMID- 15977528
TI  - ["Mrs. Benner, what is the essence of nursing?" (interview by Margrit Bachl)].

PMID- 15977529
TI  - [Empowering the patient, eliminating barriers by oneself].

PMID- 15977530
TI  - [Logopedics brings the words back].

PMID- 15977531
TI  - [Tell me how you sleep].

PMID- 15977532
TI  - [Striving for the right position].

PMID- 15977533
TI  - [Thoughts on the original title about our voluntary aid in the Baltic war].

PMID- 15977534
TI  - [Sometimes a little push is enough].

PMID- 15977536
TI  - [Love, to recover the zest of living].

PMID- 15977537
TI  - [Image of the nurse and professional choice].

PMID- 15977539
TI  - [Reasons for selection].

PMID- 15977538
TI  - [Multidisciplinary work becomes reality].

PMID- 15977540
TI  - [Payment for the insured: generalities, conditions].

PMID- 15977542
TI  - [Clinicians, who are you?].

PMID- 15977541
TI  - [Students and the ethical dimension].

PMID- 15977543
TI  - [Proactive about mutations].

PMID- 15977544
TI  - [An indispensable information system].

PMID- 15977545
TI  - [Love as medicine].

PMID- 15977547
TI  - [Clinical analysis of pulmonary actinomycosis].
AB  - A clinical analysis of four patients diagnosed as pulmonary actinomycosis in our
      respiratory division during the last seven years was performed. All of the
      patients were males with an average age of 61 years. Three patients had a past
      history. The clinical diagnosis on admission was lung cancer or pulmonary
      suppuration in three patients showing a mass-like shadow and pneumonia in one
      patient with an infiltration shadow. Suspected pulmonary infectious disease was
      detected from clinical symptoms in two patients, while suspected lung cancer was
      detected in the other two patients during health examinations. The lesions
      dominantly existed in the right upper lobe. Such findings as central low
      attenuation (LAA), bronchiectasis and pleural thickening were characteristic on
      chest computed tomography (CT). The diagnostic methods were all negative
      procedures; video-assisted thoracoscopic surgery (VATS) in two patients, a
      specimen obtained by bronchoscopy in one and a specimen taken by percutaneous
      aspiration in one. Because penicillin antibiotics were administered for a long
      time for all patients after obtaining a definite diagnosis, the prognosis was
      good and there were no relapse.

PMID- 15977548
TI  - [A study on enterovirus infection in Osaka prefecture --comparison with virus
      isolation and RT-PCR amplifying viral protein 1 region].
AB  - Detection of viral genomes with RT-PCR, which amplifies viral protein 1 region,
      as well as virus isolation was performed on 860 patients (996 specimens) who had
      been suspected for enterovirus (EV) infection in Osaka Prefecture from April 2003
      to Jury 2004. The viral positive rates of the clinical materials, combining above
      two procedures, were as follows: 48.2% from the feces, 38.3% from the throat
      swabs, and 18.0% from the cerebrospinal fluids. The positive rate by the clinical
      diagnosis indicated that herpangina was the highest at 44.7%, while encephalitis
      was the lowest at 13.4%. Out of the all specimens, the viral positive rate of RT
      PCR varied from 22.3 to 24.7%, while that of virus isolation was 15.6%. The total
      viral positive rate of both procedures combined was 29.8%. Since the detection of
      EV by RT-PCR amplifing viral protein 1 region was more rapid than virus isolation
      and superior in detection of coxsackie group A virus, RT-PCR is an effective
      procedure for diagnosis of herpangina.

PMID- 15977549
TI  - [Molecular epidemiology of Salmonella Enteritidis food poisoning by pulsed-field
      gel electrophoresis].
AB  - During the years 1983 to 1999, a total of 120 Salmonella Enteritidis (SE)
      isolates from various sources, patient's stool, foods, kitchen wear, river water
      etc., in 61 cases of food poisoning in the Sakai City, were typed by pulsed-field
      gel electrophoresis (PFGE) after XbaI or NotI digestion of chromosomal DNA. XbaI
      and NotI restriction produced 2 (X1 and X2) and 3 (N1, N2 and N3) pulse-field
      profiles, respectively. The X1 and N1 types were further divided into 8 (Xla-Xlh)
      and 6 (N1a-N1f) subtypes, respectively. However, these strains of subtypes showed
      only 0-4 fragment changes in PFGE patterns and the index of discrimination of
      over 0.75, indicating that SE isolates belong to the same clonal lineage, or are
      revealing closely clonal relationships. These results suggested a possible strain
      transmission in case of food poisoning, and epidemiologically related SE isolates
      were spread in the Sakai City district during a long period.

PMID- 15977550
TI  - [Molecular epidemiology of mechicillin-resistant Staphylococcus aureus (MRSA) by
      pulsed-field gel electrophoresis].
AB  - A total of 103 methicillin-resistant Staphylococcus aureus (MRSA) isolates from
      patients and 78 MRSA from hospital workers during the years 1990 to 1994, and 52
      MRSA from patients in year 2000, in one hospital at Wakayama Prefecture, were
      typed by pulsed-field gel electrophoresis (PFGE) profiles. MRSA isolates were
      grouped into 20 genomic types. These types were further divided into 57 subtypes.
      The type 1 was dominant among patients, and closely related type 1 strains were
      spread during 1990-1993. In contrast, the type 2 was dominant among medical
      workers in the same period. In 2000, the type 2 and 4 strains increased, and the
      diversity and complication of types appeared. The common types between the
      patients and medical workers were only type 1 to 3. Some strains isolated from
      both during the same period were shown to have the same types. Others were shown
      to be patient-specific types. These results suggest that there are complicated
      transmissions of MRSA in the hospital, i.e., the endogenous infection, patient
      patient cross infection and medical worker-patient cross infection.

PMID- 15977551
TI  - [Evaluation of seven immunological assay reagents for hepatitis B virus surface
      antigen (HBsAg) in the sensitivity and the detection of HBsAg mutants].
AB  - Mutants of hepatitis B virus surface antigen (HBsAg) are known as a cause of
      false-negative results in diagnostic tests for HBsAg; particularly when a
      diagnostic kit utilizes monoclonal antibodies to detect HBsAg. We compared seven
      HBsAg kits with regard to sensitivity for HBsAg subtypes (ad, ay) and their
      ability to detect nine different HBsAg mutants. Among them, the sensitivities of
      five kits were high and comparable to each other (0.2 - 0.3ng/ml). However, two
      kits were of lower sensitivity (0.8-1.3ng/ml, and 2.4-2.5ng/ml, respectively).
      Two kits, produced by the same company, reacted with all of the nine HBsAg
      mutants, but five kits showed false-negative results with one or more of the
      HBsAg mutants. These data indicate that there are differences in the detection
      sensitivities for HBsAg and abilities to detect HBsAg mutants among commercially
      available HBsAg kits, which may explain false-negative clinical results.

PMID- 15977552
TI  - [A case of chronic mucocutaneous candidasis cured with micafungin].
AB  - Chronic mucocutaneous candidasis (CMC) is a chronic intractable infection of
      skin, nails, and mucous membrane with Candida. Until very recently, the main stay
      of therapy had been the use of transfer factor or antifungal azole derivatives.
      Although they show definite benefits, the effects are temporal and recurrences
      are inevitable. Furthermore, the prolonged use of antifungals will sometimes
      induce resistant strains, making the treatment more difficult. Recently we
      experienced a case of CMC caused by resistant Candida spp. and treated it
      successfully with a new antifungal agent, micafungin (MCFG). The patient is a 37
      year-old woman. She was eight month, her tongue was covered with a white coat.
      Two months later, intractable cutaneous eruptions appeared on the head and back
      and the diagnosis of CMC was made. Since then she has been treated on multiple
      occasions with transfer factor, recombinant IL-2, ketoconazole or clotrimazole.
      She was referred to us because of esophageal candidiasis. On admission, oral and
      esophageal mucous membranes were thickly coated with white pseudomembranes. The
      titer of Candida antigen test was less than twice ; plasma beta-D-gulcan was
      20.14 pg/mL ; and CD4 was 376/microL. A few Candida albicans and (1+) Candida
      glabrata were cultured from oral swab. Both species were resistant to
      itraconazole but sensitive to MCFG and amphotericin B (MIC: < 0.03microg/ml for
      both). A drip infusion of MCFG (75mg/day) was started and three days later the
      oral lesions disappeared. At the end of a 2-week course of i. v. MCFG, the
      interior of the esophagus was clear. No recurrence was noted in one month. Less
      toxic than amphotericin B, MCFG will be a drug of choice in patients infected
      with azole-resistant fungi. To avoid the abuse of MCFG and the development of the
      resistant strains, the susceptibility test is recommended in every case of
      systemic candidiasis.

PMID- 15977553
TI  - [A case of infectious mononucleosis complicated with severe jaundice].
AB  - A 28-year-old male was admitted to our hospital with tonsillitis and jaundice.
      Laboratory findings showed leukocytosis (rate of atypical lymphocytes was 40%),
      liver dysfunction and hyperbilirubinemia. Epstein-Barr virus (EBV) viral capsid
      antigen (VCA) IgM and IgG antibodies were positive, and EB nuclear antigen (EBNA)
      antibody was negative. Abdominal ultrasonography demonstrated hepato-splenomegaly
      and swelling of intraperitoneal lymph nodes. A diagnosis of infectious
      mononucleosis was made due to EBV infection. Conservative therapy was given.
      Total bilirubin and alkaline phosphatase increased to maximum levels of 10.2
      mg/dl and 1,590U/l. A liver biopsy specimen revealed infiltration of lymphocytes
      in sinusoids and portal areas, focal necrosis and intrahepatic cholestasis in
      parenchyma. Liver function tests returned to normal limits and EBV VCA IgM
      antibody became negative within 10 weeks from onset.

PMID- 15977554
TI  - [DNA extraction of Chlamydophila psittaci from cloacal swabs and feces of birds].

PMID- 15977555
TI  - [Antimicrobial ceramic for killing Legionella pneumophila in hot spring waters].
AB  - Killing of Legionella pneumophila by an antimicrobial ceramic was evaluated
      during culture in nine kinds of hot spring water at 40 degrees C. After 24 hours,
      the efficacy against L. pneumophila varied, depended on water quality. The
      strongest antibacterial effect was seen in chloride hot spring water from
      Wakayama and in deionized water. In four hot spring water samples (sulfur and
      hydrogen carbonate springs from Fukushima, simple thermals from Mie, and
      radioactive spring from Tottori), the decrease was < -2 log cfu after 48 hours.
      These results suggest that the antimicrobial ceramic is able to eradicate
      Legionella from hot spring waters.

PMID- 15977556
TI  - [Cefotaxime-resistant shiga toxin-producing Escherichia coli O26 : H11 isolated
      from a patient with diarrhea].
AB  - A shiga toxin-producing Escherichia coli (STEC) O26 strain resistant to
      cefotaxime (CTX) and cefpodoxime (but not ceftazidime) was isolated from the
      faecal sample of a 17-year-old outpatient with diarrhea. The double disk synergy
      test, twin test, polymerase chain reaction and sequence analysis confirmed that
      the strain produced CTX-M-3 type extended-spectrum beta-lactamase (ESBL).
      Conjugation experiment results suggested that the CTX resistance in this strain
      was determined by an approximately 85kbp plasmid that was readily transferable to
      a susceptible recipient E. coli strain. This is the first report from Japan of
      CTX-M-3type ESBL-producing STEC O26.

PMID- 15977557
TI  - [Antimicrobial susceptibility of Campylobacter jejuni and Campylobacter coli
      isolated from human diarrheic samples].
AB  - One hundred forty-seven Campylobacter were isolated using 3,204 samples taken
      from sporadic diarrheic patients from January 2001 to December 2003. The
      detection rate of Campylobacter in 16 to 30 year old patients (12.9%, 83/641) was
      significantly higher than that in patients less than 16 years of age, 5%,
      (29/1,155) (p < 0.001) and more than 30 years of age, 2.5% (35/1,408) (p <
      0.001), respectively. The highest detection rate was obtained from the stool of
      males in the 16 to 30 year old range during the months from May to August, 26%
      (32/123). If the minimal inhibitory concentration (MIC) breakpoint for resistance
      of gentamicin (GM), erythromycin (EM), ciprofloxacin (CPFX), tetracycline (TC)
      were defined tentatively > or = 16 microg/ml, > or = 16 microg/ml, > or = 2
      microg/ml, > or = 16 microg/ml, the resistant rate would be 0.0%, 0.0%, 22.0%,
      42.8% in C. jejuni, 0.0%, 62.5%, 62.5%, 87.5% in C. coli, respectively. All the
      Campylobacter isolates were susceptible to GM. Three of the 8 C. coli isolates
      were multi-resistant in EM, CPFX, and TC. Five highly EM resistant strains with
      an MIC of > or = 512 microg/ml did not show any zone around the EM disk; 7
      susceptible strains with an MIC of less than 16 microg/ml showed = zones of 24mm
      to 36mm and revealed a good correlation with the Etest method and the agar
      dilution method. Between the two time periods of January 2001-June 2002 and July
      2002-December 2003, the resistant rate of CPFX in C. jejuni decreased from 27.5%
      to 15.5%, however, that was not significant decrease (p = 0.133).

PMID- 15977558
TI  - [Interleukin 12 measurement in the cerebrospinal fluid of infants with purulent
      meningitis].
AB  - We measured IL-12 concentrations in the CSF of patients with purulent meningitis.
      Twenty-three infants who were admitted between 1997 and 2003 and diagnosed as
      having purulent meningitis were included in this study. All patients in this
      study were admitted by the 3rd day of illness. After admission, appropriate
      antibiotics were administered to all infants. Two infants died and two other
      infants developed cerebral palsy and mental retardation (adverse outcome group).
      None of the other patients showed any neurologic abnormalities at discharge (good
      outcome group). As a control group, 16 infants who were diagnosed with diseases
      other than purulent meningitis were also investigated. The CSF IL-12 p40
      concentrations in meningitis infants on admission (median [range], 1,890 [< 15
      7,770] pg/ml) were significantly higher compared with those in the control group
      (p < 0.001). Among infants with meningitis, there were no significant differences
      on admission between patients with adverse outcome group and those with good
      outcome group. Consecutive measurements were performed in 17 infants with
      meningitis including the 2 infants with adverse outcome group. The concentration
      in the infants with adverse outcome group seemed to decrease more gradually than
      that in those with good outcome group. IL-12 induces production of interferon
      gamma, which enhances the function of polymorphonuclear leukocytes. IL-12 may
      contribute to local host defenses in the subarachnoid space.

PMID- 15977559
TI  - [Compile and evaluation of national surveillance on human echinococcosis in
      Japan, 1999 to 2002].
AB  - National surveillance on human ecinococcosis has been performed since April 1999
      when it was stipulated as a Category IV Disease under the Infectious Diseases
      Prevention Law. During the last 4 years of surveillance, 3 cases with unilocular
      hydatidosis (age range 27-81 years; median age 55 years) and 51 cases with
      alveolar hydatidosis (age range 15-86 years; median age 64 years) have been
      reported. The numbers of reported cases with alveolar hydatidosis have been
      increased with age, and the largest number reported in the age group > or = 71
      years. Three cases with unilocular hydatidosis have been reported from health
      centers in Honshu, and were likely to be imported cases. Seventeen reported cases
      had clinical symptoms. None of the reported cases had information on infection
      route. Fifty out of 51 cases with alveolar hydatid disease have been reported
      from health centers in Hokkaido. When analyzing the cases by subdividing Hokkaido
      into six regional districts, large number of cases were reported from health
      centers in Ishikari-Shiribeshi-Iburi region (20 cases) and in Nemuro-Abashiri
      Kushiro region (15 cases). As detailed addresses of the cases were masked, we
      compared the number of cases per 100,000 residents in regions. Health center in
      Nemuro-Abashiri-Kushiro region (2.13/100,000) had largest rate and second was
      Souya-Rumoi region (2.05/100,000). The results from current surveillance data
      only suggest the generation situation of human echinococcosis in several years
      ago or more, so the generation situation between 1999 April and 2002 December in
      surveillance is unknown.

PMID- 15977560
TI  - [A case of sphenoid sinusitis which could be diagnosed by orbital computed
      tomography after detected Strepotococcus pneumoniae from blood culture].
AB  - We report a case of sphenoid sinusitis which could be diagnosed by orbital CT
      after detecting Strepotococcus pneumoniae from blood culture. A previously
      healthy 47 year-old Japanese male was admitted to our hospital with severe left
      sided headache of 2 days duration. From 9 days before hospitalization (1st day),
      the patient complained of cough and sputum. On physical examination, his neck was
      supple and his temperature was 38.3 degrees C. The rest of the examination was
      normal. A chest radiograph, sinus radiograph, and head computed tomographic (CT)
      scan without contrast material disclosed no abnormalities. Lumbar puncture was
      done and cerebrospinal fluid was clear and cell counts and the levels of glucose
      and protein were normal. The peripheral white blood cell count was 14,400/fl, and
      the C-reactive protein level was 9.6 mg/dl. After blood, urine, pharyngeal mucus
      and cerebrospinal fluid cultures were obtained, empirical antibiotic therapy with
      2 gms of piperacillin twice daily was begun. He complained sever left-sided retro
      orbital headahe on the next day too. The lumbar puncture and head CT scan with
      contrast material was done again but gave no diagnostic clues. The examinations
      by the otolaryngologist, ophthalmologist and dentist found no abnormal findings.
      On the 3rd hospitalized day, Strepotococcus pneumoniae was detected from the
      blood culture taken on the 1st hospitalized day. A CT scan focused on orbita was
      done and revealed a low density area of the left sphenoid sinus. The dose of
      piperacillin was increased to 4 gms twice daily and continued for 24 days. The
      patient's headache improved and piperacillin was changed to oral levofloxacin 100
      mg, three times daily on the 26th day. The medication was stopped on the 73th
      day. Isolated sphenoid sinusitis is rare, but crtitical complications such as
      cranial nerve involvement, brain abscess, and bacterial meningitis may happen. It
      is necessary to also think of sphenoid sinusitis in practices of patients with
      severe headache.

PMID- 15977561
TI  - [Successful treatment with micafungin (MCFG) of severe peritonitis due to Candida
      parapsilosis with chronic renal failure patient on hemodialysis].
AB  - A 49 year-old woman with chronic renal failure (CRF) on continuous ambulatory
      peritoneal dialysis (CAPD) because of Goodpasture Syndrome was admitted to our
      hospital since she had a high fever and severe abdominal pain. A diagnosis of
      peritonitis was made from the physical examination and laboratory findings. The
      peritonitis was refractory to conventional antibiotics therapy. Candida
      parapsilosis was detected from dialysite. The peritonitis was aggravated although
      the antibiotic was changed to an antifungal agent (fluconazole 400mg/day).
      Fluconazole was replaced to micafungin (MCFG) and the catheter for CAPD was
      removed. The fungal peritonitis improved dramatically and beta-D glucan was
      decreased from 104 to 12.6 (pg/ml). No adverse effect was observed after using
      MCFG. It has been known that fungal peritonitis of CRF patients is refractory to
      treatment and the mortality rate is high. To our best knowledge, there is no
      report that MCFG was used for CRF patients with fungal peritonitis. However, we
      used MCFG safely and effectively for CRF patients. Therefore, it is suggested
      that MCFG is a new effective and safe antifungal agent for Candida parapsilosis
      peritonitis with CRF.

PMID- 15977562
TI  - [Host risk factors for acquirement of antimicromial resistant gene in Haemophilus
      influenzae].
AB  - The present study investigated the host risk factors for carriage of Haemophilus
      influenzae (H. influenzae) with resistant gene (s) against antibiotics. From
      September 2001 to January 2004, 174 strains of H. influenzae were isolated from
      the nasopharynx of children with respiratory tract infections. We classified
      these strains on the basis of the MIC to Ampicillin and the presence of resistant
      gene (s) for antibiotics resistance (gene for beta-lactams and altered pbp gene
      (s)). The patients' background such as previous antibiotic usage, age, daycare
      attendance, siblings and underlying diseases was investigated. The risk factor
      for carriage of strains with altered pbp gene (s) was the usage of beta-lactams
      within the last 3 months. Controlled usage of oral beta-lactams might be an
      important issue for preventing the spread of resistant H. influenzae strains such
      as beta-lactamase non-producing ampicillin resistant H. influenzae. We have to
      reconsider a therapeutic approach for the treatment of young children with
      respiratory tract infection.

PMID- 15977563
TI  - [Investigation concerning demand and vaccination applicants to traveler's
      vaccines (typhoid fever and meningococcal vaccines) not marketed in Japan].
AB  - In recent years, the number of Japanese traveling to foreign countries is
      increasing. Most of them travel to Asian regions where many infectious diseases
      that are rare or don't occur in Japan still remain endemic or epidemic. Of these
      infectious diseases typhoid fever and meningococcal infection are now preventable
      because safe and effective vaccines have been developed and now marketed.
      However, these vaccines are hardly available in Japan because the Japanese
      Government has not admitted them. To investigate the demand for the two vaccines,
      the author personally imported inactivated polysaccharide typhoid vaccine and
      groups A, C,Y and W135 combined polysaccharide meningococcal vaccine, both
      manufactured by Aventis-Pasteur. After obtaining approval of the ethical
      committee of our hospital, vaccination was started. From May 6, 2003 to September
      30, 2004, 124 applicants received typhoid vaccine and 35 were injected with
      meningococcal vaccine. Of 124 vaccinees of typhoid vaccine, 46 went to
      Afghanistan, 15 to India, 8 to Thailand. Of 35 vaccinees of meningococcal vaccine
      6 went to the USA, 5 to Guinea and 3 to England. In addition a total of 12
      physicians and nurses having no international scheduled trip were also immunized
      with meningococcal vaccine. None of these vaccines are widely known in Japan now.
      Based on our results, however, the expansion of recognition and demand for these
      two vaccines is expected.

PMID- 15977564
TI  - [Drug susceptibility and analysis using pulsed-field gel electrophoresis of
      Streptococcus pyogenes strains isolated from the patients with streptococcal
      toxic shock syndrome (STSS) in Japan].
AB  - Previously, we have performed T typing of Streptococcus pyogenes strains isolated
      from patients with streptococcal toxic shock syndrome (STSS) in Japan, and
      streptococcal pyrogenic exotoxin (SPE) typing for epidemiological examination. In
      this study, we conducted a drug sensitivity test using these strains, and
      investigated the results of gene analysis by pulse-field gel electrophoresis
      (PFGE) of S. pyogenes strains derived from patients with STSS, the patient's
      family, and patients other than those with STSS. To clarify the relationship
      between the host and bacterial factors, we investigated the association between
      clinical symptoms and T typing of the isolated strains/production of
      streptococcal pyrogenic exotoxin. There were no strains resistant to beta
      lactams, and only 1 strain was resistant to multiple agents other than beta
      lactams. The PFGE pattern of T1 type strains was classified into 2 ; the pattern
      was consistent between the strains derived from patients with STSS and those
      derived from the patient's family. The PFGE pattern of T3 type strains was
      classified into 5 (IV) ; Pattern I, which was most frequently observed, was
      detected in both the strains derived from patients with STSS/non-STSS. However,
      Patterns II and III were detected only in the strains derived from patients with
      non-STSS. Patterns IV and V were detected only in the strains derived from
      patients with STSS. When examining the association between clinical symptoms and
      bacterial factors, disseminated intravascular coagulation (DIC) was associated
      with T1-SPE B-producing strains, and pharyngitis was associated with T3-SPE A
      producing strains. In the future, the relationship between the host and bacterial
      factors should be further investigated.

PMID- 15977565
TI  - [Comparison of multidrug-resistant Salmonella enterica serovar Newport isolates
      from a patient and sewages in Fukui Prefecture].
AB  - From May 2003 to March 2004, nine strains of multidrug-resistant (MDR) Salmonella
      enterica serovar Newport were isolated from 5 sewages of 3 sewage treatment
      plants located in 2 different regions of Fukui Prefecture. Antimicrobial
      susceptibility testing identified 2 different MDR patterns (type I and II). Type
      I strains were resistant to ampicillin, tetracycline, streptomycin,
      chloramphenicol, amoxicillin/clavulanic acid, sulfisoxazole, cefotaxime,
      cephalothin, ceftriaxone, and ceftrazidime and type II strains were additionally
      resistant to sulfamethoxazole-trimethoprim and spectionomycin. Neither of
      kanamycin, fosfomycin, nalidixic acid, gentamycin, or ciprofloxacin resistance
      was observed. Type I and II strains were different in pulsed-field gel
      electrophoresis patterns and plasmid profiles, while they showed the same
      profiles with in each type. All the MDR strains in this study were proved to
      carry the blaCMY-2 gene by PCR and sequence analyses. Numbers of reports on MDR
      S. Newport with blaCMY-2 have been increasing in foreign countries such as the
      United States. The MDR patterns of the isolates in this study were similar to
      those of the United States. These properties of the type I strains were identical
      with that a strain isolated from a 7-year-old patient in Fukui Prefecture, in
      September 2003 which we previously reported. However, the patient lived in a
      region where no epidemiological associations with the sewage treatment plants
      were found. This suggests that the MDR strains might prevail in Fukui Prefecture.
      Domestic surveillance for MDR S. Newport would be need.

PMID- 15977566
TI  - [The clinical usefulness of a newly rapid diagnosis kit, detection of respiratory
      syncytial virus].
AB  - ImmunoCard STAT! RSV (Meridian Bioscience, Inc, USA) is a rapid immunoassay
      method newly developed for detection of respiratory syncytial virus (RSV) by
      immunochromatography. We carried out an evaluation of the ImmunoCard STAT! RSV.
      One hundred fifty-nine nasal wash samples and nasopharyngeal aspirates from
      patients were used to evaluate three different kits, which are ImmunoCard STAT!
      RSV, RSV testpack (Abbott JAPAN) and Directigen EZ RSV (Nippon Becton, Dickinson
      and Company) . One hundred twenty-eight samples showed equivalent results. When
      nested reversed transcription-PCR (nested RT-PCR) results for 31 samples showing
      discrepancies among three kits, 10 samples were positive, and 21 samples were
      negative by nested RT-PCR. Compared to Nested RT-PCR results, ImmunoCard STAT!
      RSV showed a sensitivity of 90.5% (19/21) and a specificity of 80.0% (8/10), as
      well as RSV testpack showed a sensitivity of 10.0% (2/21) and a specificity of
      100% (10/10), Directigen EZ RSV showed 95.2% (20/21) and 0.0% (0/ 10),
      respectively. Furthermore, the detection limits were also evaluated by using ACTT
      No. VR1540 for RSV A-2 strain, and ACTT No. VR1401 for Wash strain. The detection
      limit of ImmunoCard STAT! RSV was 5.15 x 10(6) TCID50/mL in subgroup A strain and
      was 7.58 x 10(5) TCID50/mL in subgroup B strain. This result was similar to RSV
      testpack, and was better than the detection limit of Directigen EZ RSV. It is
      concluded that ImmunoCard STAT! RSV is useful in detecting RSV in a clinical
      setting with equivalent performance to conventional other detecting kits.

PMID- 15977567
TI  - [Successful treatment with micafungin in a case of candidemia associated with
      pneumonia].
AB  - A 63-year-old woman was admitted to our hospital with fever and cough. Candidemia
      was diagnosed by blood culture and culture of IVH catheter. Although, the patient
      was treated with fluconazole, clinical symptoms and chest radiographic findings
      worsened. After micafungin was replaced with fluconazole, her symptoms, chest
      radiographic findings improved and stabilized. It is suggested that micafungin is
      useful for the treatment of candidemia associated with Candida parapsilosis.

PMID- 15977568
TI  - [A travel abroad-associated case of Legionella pneumonia diagnosed by urinary
      antigen detection test].
AB  - A 75 year-old male was admitted to our hospital with high fever and dyspnea. He
      had traveled in Turkey 10 days before. His chest X-ray showed infiltrations in
      bilateral lower lung fields. His urinary antigen detection test for Legionella
      pneumophilia was positive. He was treated with pazufloxacin added to
      clarithromycin and his symptons were promptly resolved.

PMID- 15977570
TI  - [Comparison between biotype of Vibrio cholerae O1 and genotype using polymerase
      chain reaction].
AB  - To compare between biotype of Vibrio cholerae O1 and genotype using polymerase
      chain reaction (PCR), 9 classical and 81 El Tor biovar strains were investigated
      for hemolysis, agglutination of avian erythrocytes, VP test reactivity,
      sensitivity to both polymyxin B and classical phage IV, and genotype using PCR
      amplification of hlyA, tcpA, rtxA and rtxC. One classical biovar strain showed
      atypical reaction upon agglutination of avian erythrocytes. Eighteen El Tor
      biovar strains showed atypical reactions, with the exception of sensitivity to
      polymyxin B. By PCR detection of hlyA, rtxA and rtxC amplifications, all
      classical biovar strains possessed only classical type hlyA, while all El Tor
      biovar strains possessed El Tor type hlyA, rtxA and rtxC. By PCR analysis of
      amplicons, all classical biovar strains possessed classical type tcpA. One ctx
      negative El Tor biovar strain possessed degenerated classical type tcpA and 4 ctx
      negative El Tor biovar strains had no detectable tcpA. These results indicated
      that genotype of V. cholerae O1 using PCR detection of hlyA, rtxA and rtxC was
      consistent with biotype of the organism, suggesting that analysis of the genotype
      of the organism was as effective as by biochemical properties. However, PCR
      detection of hlyA is most appropriate for the biotyping of V. cholerae O1, as
      compared to biochemical properties, since El Tor biovar was originally
      distinguished from classical biovar strains by the hemolytic reaction.

PMID- 15977569
TI  - [A case of leptospirosis caused by Leptospira borgpetersenii serovar sejroe
      infected in Bali Island, Indonesia].
AB  - We report a patient with leptospirosis caused by Leptospira borgpetersenii
      serovar Sejroe infection on Bali Island, Indonesia. This 33-year-old Japanese man
      had stayed at a resort hotel on the island from July 8 to July 13 2004. At the
      hotel, he swam in the pool, walked barefoot, and lied down in the grass. He
      developed a high fever and headache 7 days after completing his trip, and was
      admitted to our hospital on July 23. On admission he showed conjunctival
      suffusion and complained of myalgias. Laboratory findings included granulocytosis
      and elevated CRP. Plasmodium spp. were not found in blood smears, and no
      pathogenic bacteria were isolated from blood or fecal cultures. We diagnosed the
      patient as leptospirosis upon detection of slender coiled organisms with
      characteristic morphology by darkfield examination of blood sample. Minocycline
      100 mg i.v.b.i.d. showed excellent efficacy. A microscopic agglutination test
      (MAT) during the convalescent stage demonstrated a significant increase in
      antibodies against L. borgpetersenii serovar Sejroe, confirming the diagnosis of
      leptospirosis. Despite occurrence of a pandemic of leptospirosis in certain
      Southeast Asian countries including Indonesia, information concerning pandemic
      disease is limited. In addition serovars of "imported" cases representing
      infection in pandemic areas differ widely from those in domestic cases. Adequate
      laboratory support therefore is crucial for accurate diagnosis of leptospirosis.

PMID- 15977571
TI  - [Isolation of enteroaggregative escherichia coli (EAggEC) from patients with
      diarrheal disease in an outbreak case of overseas tour].
AB  - Twenty four patients out of 78 Cambodia tourists (31%) suffered from diarrhea
      and/or abdominal pain. Though the stools of 20 patients were examined in some
      local health centers and institutes, well-known pathogens were detected in only a
      low level and the cause of the outbreak remained unclear. We suspected the
      enteroaggregative Escherichia coli (EAggEC) as a cause of this outbreak. We
      examined E. coli strains isolated from stools of 8 patients (Okayama:7, Aichi:1)
      at first by the PCR method targeted both the aggR and the astA genes related to
      the virulence factors of EAggEC. As a result, the E. coli strains with positive
      aggR and/or astA genes were isolated from 8 patients. And the E. coli strains
      with positive both aggR gene and clump formation isolated from 3 patients adhered
      aggregatively to HEp-2 cells and accordingly identified as EAggEC. The plasmid
      profiles, PFGE patterns and drug resistance patterns of these EAggECs agreed
      completely. From these results, we concluded that at least 3 patients were
      infected with EAggEC of the same origin. Though we could not examine all samples
      from 20 patients, it is possible that the still uncommon EAggEC might be a cause
      of the outbreak. The E. coli strains with positive aggR gene did not always
      aggregatively adhered to HEp-2 cells. So we recommend to perform stepwise EAggEC
      screening tests by the PCR and the clump formation, and final confirmation test
      by the aggregative adhesion to HEp-2 cells.

PMID- 15977572
TI  - [Study of the antibodies against measles, rubella, mumps and varicella-zoster
      viruses in sera from the medical staffs].
AB  - For infection control against measles, rubella, mumps and varicella-zoster
      viruses in the hospital, it is important to assess the immunity of the medical
      staff against those viruses and to achieve high immunocompetence in the medical
      staff by vaccination. We estimated the specific antibodies against measles,
      rubella, mumps and varicella-zoster viruses by ELISA in 686 care workers (240
      men, 446 women) of Yamagata University Hospital. The members (frequencies)
      without antibodies for each virus were 59 (8.6%) for measles virus, 68 (9.9%) for
      rubella virus, 104 (18.2%) for mumps virus and 5 (0.7%) for varicella-zoster
      virus. The ratios of positive antibodies, especially against rubella and mumps
      viruses, were higher among women than men. To see the relationship between the
      immunity and age, we studied the numbers without antibodies by dividing the
      persons by age. The numbers of negative IgG for measles virus were 45 (17.5%) in
      the persons age of 21-30, 8 (4.3%) in 31-40, 4 (2.4%) in 41-50 and 2 (2.7%) in
      over 51. The numbers of negative IgG for rubella virus were 21 (8.2%) in the
      persons age of 21-30, 22 (11.7%) in 31-40, 22 (13.2%) in 41-50 and 3 (4.1%) in
      over 51. The numbers of negative IgG for mumps virus were 35 (13.6%) in the
      persons age of 21-30, 39 (20.7%) in 31-40, 22 (13.2%) in 41-50 and 8 (10.8%) in
      over 51. The numbers of negative IgG for varicella-zoster virus were 4 (1.6%) in
      the persons age of 21-30 and 1 (0.5%) in 31-40. The rate of the persons without
      antibodies but who had received vaccination in the past were the following: 46%
      for measles virus, 21% for rubella virus and 21% for mumps. The results of
      antibodies were informed individually and the persons without antibody against
      each virus were recommended to receive a vaccination for each virus.

PMID- 15977573
TI  - [Non-specific reactions in four methods measuring (1-->3)-beta-D-glucan levels in
      plasma].
AB  - We detected non-specific reactions in the measurement of (1-->3)-beta-D-glucan
      levels (beta-glucan) in plasma, and the influences of the non-specific reactions
      on sensitivity and specificity of measurement methods were examined. In this
      study, 460 plasma samples from 174 patients at Kawasaki Medical School Hospital
      were used, and the plasma beta-glucan levels were measured by different four
      methods. The methods included the dilution-heating-endpoint (DHE), dilution
      heating-turbidimetric (DHT), alkaline-kinetic (AK), and alkaline-endpoint method
      (AE) with and without 4-amidinophenyl benzoate hydrochloride (APB) of a protease
      inhibitor blocking the Limulus reaction. Non-specific reactions were detected
      from the calculated value under conditions with APB. Therefore, both of the
      actual values and the values equivalent to non-specific reactions were
      calculated. The incidence of non-specific reactions was 2.4% in DHE method, 0% in
      DHT, 53.3% in AK, and 99.3% in AE. The sensitivity and specificity in the methods
      were 35.7% and 96.0%, 28.6% and 96.0%, 78.6% and 80.1%, and 57.1% and 84.1%,
      respectively. When subtracted the non-specific reaction values from the actual
      values in AK and AE method, the specificity was increased by 91.4% and 94.0%,
      respectively. In these two methods, the non-specific reaction was considered to
      be a major cause of the low specificity. Finally, to measure plasma beta-glucan
      levels accurately, non-specific reactions should be excluded as possible by
      further improvement of measurement methods.

PMID- 15977575
TI  - [Cross-induction of HI antibody against A (H3N2) of influenza HA vaccine].

PMID- 15977574
TI  - [Three sisters of pulmonary Mycobacterium avium complex disease].
AB  - We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease.
      The oldest sister was complaining of bloody sputum, and cultures were positive
      for M. avium. By monotherapy with clarithromycin, symptom and imaging findings
      had shown no progression for six years. The second sister was complaining of
      productive cough, and cultures were positive for M. intracellulare. Her symptom
      and imaging findings had shown no progression for seven years without any
      treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and
      cultures were positive for M. intracellulare. Although she received chemotherapy
      with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging
      findings had progressed gradually. She died of respiratory failure four years
      later. Autopsy findings revealed no disseminated MAC disease. The results which
      three cases showed different isolate patterns and clinical courses suggest the
      importance of underlying anti-mycobacterial immunological impairment and defects
      of local host defense rather than virulence of infected strains as the
      pathogenesis of pulmonary MAC disease.

PMID- 15977576
TI  - [EBM for surgeons].

PMID- 15977578
TI  - [The application of extended resection for non-small cell lung cancer].
AB  - Lung cancers invading the neighboring anatomic structures such as the chest wall,
      diaphragm, great vessels, and tracheal carina are categorized as T3 or T4 and
      regarded as locally advanced lung cancer. These patient populations should be
      treated with an aggressive, multidisciplinary approach with surgery,
      chemotherapy, and radiotherapy in a manner that maximizes the chance for long
      term cure while minimizing the overall risks of treatment. The surgical
      indications, mode of resection, and combined treatment for these tumors have been
      important issues. However, the scientific evidence from comparative studies,
      which serve as the basis for practice guidelines, is very scant for these
      categories of tumor. Although surgical interventions are favored for tumors
      simply invading the chest wall the combined resection of the great vessels, such
      as the superior vena cava, aorta, and left atrium, is not standardized. The
      further refinement of scientific evidence that justifies the therapeutic strategy
      is necessary, especially for these tumor categories. In the future, molecular
      diagnostic markers may allow more accurate means of assessing which patients with
      locally advanced non-small cell lung cancer will receive the greatest benefit
      from surgery or other forms of treatment.

PMID- 15977579
TI  - [Perioperative management of extended surgery for advanced lung cancer].
AB  - Extended surgery for advanced non-small cell lung cancer includes combined
      resection of T3 or T4 organs and extended lymph node dissection in N2 or N3
      cases. It is well known that the incidence of complications with extended surgery
      is higher in comparison with standard surgery due to the greater extent of
      invasiveness of the former. The management of extended surgery patients requires
      an understanding of the characteristic complications and their frequency for each
      type of surgery. Perioperative management including an accurate preoperative
      diagnosis and the prevention of postoperative complications affects prognosis
      because mortality rate is higher in patients in whom more complications occur.

PMID- 15977580
TI  - [Surgery for stage III lung cancer].
AB  - The standard treatment for superior sulcus tumor has been considered preoperative
      radiotherapy followed by surgery since Paulson proposed. Excellent results of
      preoperative chemo-radiotherapy reported will be change the standard therapy for
      superior sulcus tumor. The results of combined resection of neighboring organs
      for lung cancer have been reported recent a couple of decades. Those results
      makes clear the limit of improvement of survival after surgery alone for IIIA
      lung cancer. Multi-disciplinaly treatment including surgery should be tried as
      clinical trials for IIIA lung cancer. The reports of surgery for IIIB lung cancer
      are limited number of patients and unstable results. A lot of pure surgical
      problems of surgery for IIIB lung cancer sill remain to be solved. We should
      strongly promote clinical trials including surgical approaches for locally
      advanced lung cancer.

PMID- 15977582
TI  - [Surgical procedure of thoracoscopic and video-assisted anatomical segmentectomy
      for small peripheral lung cancer].
AB  - Recently, small peripheral lung cancers which is indicated limited resection are
      frequently found by HRCT or PET. The limited resection for lung cancer includes
      thoracic and video-assisted anatomical segmentectomy (VATS segmentectomy) and
      wedge resection of the lung parenchyma. In anatomical segmentectomy, intra
      plumonary lymph nodes are dissected, on the other hand, those lymph nodes can not
      be dissected in wedge resection. Consequently, segmentectomy will be radical
      procedure for lung cancer compared with wedge resection. Thoracic surgeons are
      required to perform anatomical segmentectomy for small peripheral lung cancer.
      The anatomical segmentectomy is not familiar procedure for recent thoracic
      surgeons. Thoracic surgeons should be skilled in that procedures. This is a
      review of basic procedures of VATS segmentectomy for lung cancer for young
      thoracic surgeones.

PMID- 15977581
TI  - [Review and evaluation of limited resection for early lung cancer].
AB  - Limited resection for early lung cancer has been associated with significantly
      higher local recurrence rates based on previous reports such as those from lung
      cancer study groups. On the other hand, a few groups demonstrated that patients
      with small peripheral cancer who undergo limited resection have comparable
      survival rates with those who undergo lobectomy. Recent advances in radiologic
      investigation and pathologic analysis have broadened the indications for limited
      resection. Since the introduction of the adenocarcinoma classification by Noguchi
      surgery for localized bronchioloalveolar carcinoma has focused on limited
      resection. Caution is necessary when performing wedge resection even if 10 mm or
      less in diameter and in compromised segmentectomy for early lung cancer. Although
      limited resection is still controversial intentional segmentectomy for localized
      bronchioloalveolar carcinoma or less than 20 mm or less in diameter may be
      recommended without evidence-based medicine. It is important to accumulate
      further evidence clarifying the survival and function benefits of limited
      resection. New therapeutic modalities for limited surgery for small-sized lung
      cancer may increase patient life expectancy.

PMID- 15977583
TI  - [Extended segmentectomy for small-sized peripheral CN0 non-small cell lung
      cancer].
AB  - With advances in diagnostic imaging techniques, small-sized lung cancers are now
      diagnosed much more often. Lobectomy has been the standard surgical procedure
      even for small lung for decades. Is it necessary to remove uniformly such a large
      amount of lung tissue for all tiny cancers? Extended segmentectomy as an
      intentional lesser resection for a peripheral clinical N0 lung cancer tumor 2 cm
      or less in diameter in patients able to tolerate a lobectomy, in which the
      resection line of the lung is placed beyond the burdened segment if required for
      sufficient margins, requires confirmation of surgical N0 disease by
      intraoperative examination of lymph node frozen sections. The procedure should be
      converted to standard lobectomy if the sections are positive. Recently, several
      reports have suggested that the prognosis after lesser resection in such highly
      selected patients is no worse than that following standard lobectomy. In addition
      to preservation of pulmonary function, this lung-saving surgery provides a second
      chance to patients who have a higher risk of metachronous disease after surviving
      the first disease. Extended segmentectomy might be an alternative standard
      surgery for patients with small peripheral lung cancers. However, patient
      selection with intraoperative pathologic examination and accurate technique with
      wide lesion margins must be strictly adhered to.

PMID- 15977585
TI  - [Fibrocytes in tissue fibrosis].

PMID- 15977586
TI  - [What we can learn from a case of medical malpractice].

PMID- 15977587
TI  - [Health behavioral factors related to the attitude toward quit-smoking among
      factory workers].
AB  - PURPOSE: It is important to focus on various characteristics of people to promote
      measures for quitting-smoking. Using the Health Belief Model, we here
      investigated social and psychological factors related to willingness to cease
      smoking among factory-workers in the northern part of Kyoto Prefecture. METHOD:
      From October to November 2001, the 810 subjects were surveyed about their smoking
      behavior and related factors using an unsigned self-administered questionnaire.
      Among the 534 respondents, we performed logistic regression analysis, considering
      7 factors ((1) age, (2) susceptibility, (3) seriousness, (4) benefits, (5)
      barriers, (6) mass-media and (7) advice from others) as independent variables and
      interest in smoking cessation as a dependent variable. Four comparisons ((1) "no
      interest" vs "precontemplation or contemplation", (2) "no interest" vs
      "precontemplation", (3) "no interest" vs "contemplation", (4) "precontemplation"
      vs "contemplation") were conducted for 239 males who were current smokers at the
      time of the survey. RESULTS: Acceptance of the benefits of smoking cessation
      showed a significant positive association with willingness to quit smoking, with
      Ors for comparisons of "no interest" vs "preconemplation or contemplation", "no
      interest" vs "precontemplation", and "no interest" vs "contemplation" (odds
      ratios (95%CI) of 3.06 (1.76-5.31), 2.78 (1.58-4.90), 4.41 (1.75-11.15),
      respectively). Acceptance of the seriousness of health hazards from smoking had a
      significant positive association with the willingness to quit (odds ratio (95%CI)
      was 1.88 (1.02-3.46)). CONCLUSION: It is can be concluded that it is useful to
      enhance subjective recognition of the benefits of not-smoking and the seriousness
      of the harm caused by smoking, to increase the level of willingness of quitting
      from "no interest" to "precontemplation" or "contemplation".

PMID- 15977588
TI  - [Dietary habits, attitudes toward weight control, and subjective symptoms of
      fatigue in young women in Japan].
AB  - PURPOSE: This paper describes dietary habits and attitudes toward body weight
      control of college women in Japan and examines their relationships with
      subjective symptoms of fatigue. We also discuss strategies to promote better
      diets among young adults. METHODS: Self-reported questionnaires were distributed
      to 286 young women aged 18 to 25 years; 275 of these were analyzed. RESULTS: The
      study found that more than half of the women were concerned about nutritional
      balance and calories. Yet thirty percent ate "a single-item meal (i.e., bread,
      rice bowl, noodles) two or more times a day," while roughly one half skipped
      breakfast "sometimes" or "always." A majority ate vegetables "almost never" and
      consumed instant foods, confectionery, or sugary drinks "almost daily."
      Subjective symptoms of fatigue were significantly correlated with a higher
      frequency of irregular meal-taking, single-item meals, between-meal snacking,
      missed breakfasts, non-vegetable diets, non-fruit diets, and instant foods and
      confectionery. About sixty percent of the women in the study considered their
      bodies to be "slightly fat or overweight" while 79.5% indicated a desire to "lose
      weight". On average, the participants' ideal BMI was 18.7 (+/- 1.2) while the
      ideal body weight was 47.2 (+/- 4.1) kg, approximately 4 kg under actual average
      body weight. Subjective symptoms of fatigue were stronger among women who
      considered themselves "slightly fat or overweight". Likewise, symptoms were
      stronger to the extent that a participant's ideal BMI was below her actual BMI.
      CONCLUSION: Many women in this study desired to lose weight although they were
      not overweight by objective measures. The study suggests that subjective symptoms
      of fatigue are not the result of individual dietary habits, but rather of a
      lifestyle that reach to series of dietary habits connected to subjective symptoms
      of fatigue. The study also confirms the importance both of encouraging young
      women not just to eat well but to lead lifestyles in which they do not skip meals
      and of efforts that might help them to evaluate their own bodies more
      objectively.

PMID- 15977589
TI  - [Mental health and related factors with family caregivers for elderly in special
      care nursing homes for the aged].
AB  - PURPOSE: The purpose of this study was to examine the mental health and related
      factors with family caregivers for the elderly in special-care nursing homes for
      the aged. METHODS: We conducted a questionnaire survey among family caregivers
      for elderly living in three special-care nursing homes in Tokyo. The
      questionnaire included factors from the General Health Questionnaire-28 (GHQ-28)
      pertaining to family caregivers, the elderly, and the relationships between them.
      The GHQ-28 was used to measure the mental health of the caregivers and a logistic
      regression model was applied for the analysis. RESULTS: Of the 145 family
      caregivers surveyed, 59 (40.7%) exhibited low mental health (GHQ-28> or = 7). The
      logistic regression analysis revealed that family caregivers with low mental
      health had lower social support (OR: 0.10 (0.03-0.29)) and had longer visiting
      times (OR: 5.80 (1.79-18.82)). DISCUSSION: The results suggested that many family
      caregivers for elderly persons in institutions may have poor mental health and
      that it is necessary to provide them with support. It is concluded that self-help
      groups for families and the promotion of communication between the elderly and
      their family caregivers might be effective for this purpose.

PMID- 15977590
TI  - [Prevalence of intimate partner violence and related factors in a local city in
      Japan].
AB  - OBJECTIVES: This study sought to assess the prevalence of intimate partner
      violence in a local city of Fukui Prefecture, and whether the subjects' and their
      partners' demographic characteristics, alcohol use, and violence experienced in
      the families in which they were raised might be related risk factors. METHODS: We
      conducted a mail survey of 1,000 subjects aged 20-69 in the city randomly sampled
      from the population of 45,220 that were stratified by 10 years of age and sex and
      pulled 100 from each group. Data from two 248 respondents were eligible for
      analysis. The self-administered questionnaire included items on; 1) whether they
      were the victims of physical, sexual, social-economic and psychological violence
      from their intimate partners, and whether they perpetrated violence or not on
      their partners; 2) demographic characteristics of the subjects and their partners
      with information on gender, age, occupation, educational background, annual
      income, the cohabitants, and their alcohol use; 3) the subjects' experience of
      violence in the family in which they had grown up; exposure to violence between
      their parents, and being abused by them. RESULTS: Out of 248 subjects, men
      accounted for 41.5%. The prevalence rate of any violence experienced from
      intimate partners was 46.4%, and that of having perpetrated any violence on the
      partner was 43.1%. Women reported experiencing more "sexual violence" from their
      partners than did men. In addition, men admitted to more "physical, sexual, and
      psychological violence" on their partners than women. Those who had themselves
      been exposed to violence between parents or were victimized by their parents
      significantly had more experience of violence from their partners and
      perpetration than those who did not. CONCLUSION: The results suggest that
      questioning about the experience of violence in the family is useful for the
      early detection of intimate partner violence.

PMID- 15977591
TI  - [Methodology of retrospective chart review to detect adverse events: the
      reliability of physician judgment].
AB  - PURPOSE: To establish a scientific basis for promoting patient safety, basic
      information related to the incidence of adverse events (AEs) is needed. In
      studies in several other countries, trained nurses screened for potential AEs
      using explicit criteria in the first stage, and physicians reviewed selected
      charts in the second stage. To assure the accuracy of retrospective chart review,
      it is important to verify the reliability of AE judgments by physician reviewers.
      The purpose of this study was to test this reliability of judgment of AEs (their
      presence, causation of healthcare management and preventability) by three
      physician reviewers. METHODS: This study used 100 selected charts of non
      psychiatric inpatients in an acute care hospital. Three physicians independently
      assessed AEs and discussed their judgments with the physician who created the
      manual for judging AEs. We considered judgments of the AEs agreed on by the four
      physicians to be final AE judgments and compared the reliability of each measure
      related to AE judgments among the physician reviewers using the kappa statistic.
      RESULTS: The number of AE cases each physician reviewer judged ranged from 18 to
      27. Agreement on the presence of an AE ranged from 83.0% to 90.0% (kappa=0.52
      0.70). Ultimately, AEs were judged to have occurred in 16 cases while 7 cases
      were deferred. The agreement on the presence of an AE between the physician's and
      the final judgment ranged from 86.0% to 96.8% (kappa = 0.56-0.88). However,
      agreement on the causation of healthcare management and preventability between
      the physician's and the final judgment was not in the acceptable range.
      CONCLUSION: The reliability of each physician's judgments regarding the presence
      of an AE was satisfactory. However, the reliability of judgments related to the
      causation of health care management and preventability was not necessarily
      satisfactory. Therefore, it is considered important to judge causation and
      preventability based on discussion with clinical experts in the relevant field.

PMID- 15977592
TI  - [Effects of shift work on quality of sleep among retired workers].
AB  - To examine the relationship between shiftwork experience and quality of sleep
      after retirement, we carried out a self-reported questionnaire survey on 777
      retired workers of a manufacturing company. Questionnaire items included past
      illness, current health status, dietary habit, alcohol drinking, smoking, regular
      exercise, sleep, working condition (job, shift work experience, shift work
      periods and side job), current working status, social activity, educational
      background, sex, age and number of years since retirement. Present health status
      (adjusted odds ratio 4.318, 95% CI 2.475-7.534), shift work experience (2.190,
      1.211-3.953), present working status (1.913, 1.155-3.167) and dietary habit
      (1.653, 1.055-2.591) were significantly related to sleep disturbance after
      retirement by multiple logistic regression analysis. To prevent sleep disturbance
      after retirement, people should keep a regular lifestyle and good health status,
      especially ex-shift workers.

PMID- 15977593
TI  - [Worker's exposure and dust control in metal grinding operations].

PMID- 15977594
TI  - [Waist circumference as a health index and its related factors].
AB  - There are many health indexes such as Body Mass Index (BMI), however, very few
      studies have reported about waist circumference. The purpose of this study was to
      investigate the relationship between waist circumference and BMI, and
      relationships with diet and daily life. The subjects were 213 males aged over 35
      yr. A self-report questionnaire was used to survey subjects, and waist
      circumference was measured and a blood sample taken. The subjects with abnormal
      BMI and blood tests, blood pressure, TG, GPT and gamma-GTP, had waist
      circumferences were larger than the normal blood test group. Groups of subjects
      who ate fried-food, were eating out 4 or 5 times per week (p = 0.004), or
      exercising 2 to 3 times per week had waist circumferences which were larger than
      the other groups. Multivariate logistic regression analysis revealed that the
      subjects who had a disease (OR: 2.10, p = 0.046), or an abnormal blood test (OR:
      3.54, p = 0.009) had a significantly larger waist circumference. According to
      these results, waist circumference could be a health index. The people who ate
      less fried-food or exercised kept normal waist circumferences which protected
      them from internal obesity.

PMID- 15977595
TI  - [Study on clostridium difficile-associated diarrhea suspected as nosocomial
      infection in urology ward].
AB  - Between June 2000 and January 2001, 11 patients were diagnosed with Clostridium
      diffcile (C. difficile)-associated diarrhea in the ward of urology at the
      Kakegawa Municipal Hospital. Of these 11 patients, 10 had exposure to
      antimicrobial agents, before the onset of diarrhea. All patients' stools were
      positive for C. difficile toxin A. After discotinuing antimicrobial agents with
      or without administering Vancomycin, they recovered from C. difficile-associated
      diarrhea. Between January 2001 and September 2002, 17 patients who were diagnosed
      with C. difficile-associated diarrhea in our hospital were classified into two
      types by PCR ribotyping. Therefore, we suspected a nosocomial outbreak of
      diarrhea caused by C. difficile.

PMID- 15977596
TI  - [Utility of ureteral stent for stone street after extracorporeal shock wave
      lithotripsy].
AB  - We reviewed the records of the 530 patients with urinary stones (renal stones:
      243; ureter stones 287) who received extracorporeal shock wave lithotripsy (ESWL)
      (MFL5000; Dornier), from January 1995 to July 2002, retrospectively and
      determined whether the ureteral stent affected the incidence rate of stone street
      (SS). We also assessed the effect of ureteral stent on the subsequent management
      for SS. Forty patients (7.5%) developed SS. Twenty patients were inserted a
      ureteral stent prior to ESWL (stent group), and 20 patients were performed ESWL
      without a ureteral stent (in situ group). In the stent group, the most common
      (80.0%) location for SS was in the upper third ureter, while in the in situ
      group, SS mostly developed in the distal third ureter (60.0%). The incidence of
      SS did not differ significantly between the two groups when the size of renal and
      ureter stones was below 30 and 20 mm, respectively. When the renal stones were
      larger than above 30 mm, the incidence of SS in the stent group was significantly
      higher than that in the in situ group. SS disappeared spontaneously with stone
      passage in 10 of the patients in in situ group, but in only 1 patient in the
      stent group. In the stent group, 15 patients were treated for SS by removal of
      ureteral stent regardless of stone diameter. We conclude that ESWL should be
      performed without a ureteral stent when the stone diameter is below 20 mm. When
      the ureteral stent is thought to interfere with the delivery of stone fragments,
      the decision to remove it should be made as soon as possible.

PMID- 15977597
TI  - [Four cases of idiopathic retroperitoneal fibrosis markedly responsive to steroid
      therapy].
AB  - We report four cases of idiopathic retroperitoneal fibrosis (IRPF) effectively
      treated with steroid therapy. Computed tomographic (CT) scan showed the density
      of soft tissue mass enveloping the abdominal aorta in four cases. From
      radiographic findings we made a diagnosis of IRPF. Management with steroid
      therapy over three months improved general symptoms and radiographic findings.
      Prominent calcification in the wall of the abdominal aorta indicated that the
      arteriosclerosis was related to IRPF. We measured serum antibodies for Chlamydia
      pneumoniae in four cases.

PMID- 15977598
TI  - Asymptomatic adrenal medullary hyperplasia detected with intraoperative
      hypertension: a case report.
AB  - We report a rare case of asymptomatic adrenal medullary hyperplasia detected by
      chance with intraoperative hypertension during surgery for ipsilateral renal cell
      carcinoma. A 41-year-old male visited our hospital with a complaint of left flank
      pain. He had normal blood pressure and plasma catecholamine level was within
      normal limits. Ultrasonogram and CT scan revealed a left renal tumor but did not
      showed any abnormal masses in the left adrenal gland. The clinical diagnosis was
      renal cell carcinoma and we performed left total nephrectomy. In the process of
      operative manipulation, however, the blood pressure and pulse rate of this
      patient showed a marked increase. Pathological examination of the extirpated
      kidney revealed renalcell carcinoma, while the resected adrenal gland was
      diagnosed as adrenal medullary hyperplasia.

PMID- 15977599
TI  - [A case of accelerated acute rejection in kidney transplantation rescued by
      plasma exchange].
AB  - A 30-year-old female received living donor kidney transplantation from her
      mother. The surgical procedure was uneventfully performed and urine output was
      observed a few minutes after reperfusion. However, 24 hours after the surgery,
      the urine volume rapidly decreased with worsened renal blood flow as determined
      by Doppler ultrasonography, diagnosed as accelerated acute rejection (AAR).
      Plasma exchange (PE) combined with therapies including administration of steroids
      and OKT3 dramatically improved the renal status, resulting in maintenance of good
      renal function (serum Cr; 1.5 mg/dl) even after 18 months PE was considered as a
      powerful tool for AAR, and the literature was reviewed.

PMID- 15977600
TI  - [A case report of cholesteatoma of the ureter difficult to distinguish from
      malignant ureter tumor].
AB  - An 81-year-old woman consulted us with low abdominal pain. A computed tomography
      (CT) image showed left hydronephrosis and a mass without calcification at the
      lower portion of the left ureter. A retrograde urogram showed an irregular
      filling defect at the lower portion of the left ureter that suggested an
      obstruction by a malignant ureter tumor. Therefore, total nephroureterectomy was
      performed. The surgical specimen showed a mass with a membrane, which could be
      detached easily from the ureter wall. The ureter wall showed hyperkeratosis upon
      histological examination, and the mass was diagnosed as cholesteatoma.

PMID- 15977601
TI  - [A case of a ureteral inflammatory pseudotumor].
AB  - The patient was a 28-year-old woman. In February 2002, she visited another
      physician due to acute pyelonephritis. Based on CT findings, a lower ureteral
      stricture caused by a benign extraureteral tumor was diagnosed. The patient was
      being monitored by periodic exchange of ureteral stents. In February 2003, the
      patient visited our department seeking a second opinion. Retrograde pyelography
      showed an elliptical filling defect in the lower urinary tract. Ureteroscopy
      showed that the surface of the tumor was mostly smooth, regular and partially
      papillary. Biopsy was performed, and histological analysis revealed only
      nonspecific inflammation. In December 2003, based on a diagnosis of benign
      ureteral tumor, we performed partial resection of the right urinary tract and
      ureterocystoneostomy. As rapid intraoperative pathological analysis confirmed an
      inflammatory pseudotumor, total nephroureterectomy was avoided.

PMID- 15977602
TI  - Mullerian duct remnant involving Wolffian system: a case report and literature
      review.
AB  - A 14-month-old boy with repeated left acute epididymitis was admitted to our
      department. Ultrasonography detected a midline round cystic mass in a
      retrovesical region. This was easily opacified by cystourethrography and seen to
      have a free communication with the posterior urethra. Since urethroscopy revealed
      a passable orifice in the center of the verumontanum, while a cystic-wall biopsy
      specimen showed squamous epithelium, we considered this cystic lesion to be an
      enlarged prostatic utricle. Vasography showed that the bilateral vasa was
      implanted directly into this cystic lesion, and was the possible cause of his
      left epididymitis. Ligature of the left vas deferens was performed to prevent
      left epididymitis. An enlarged prostatic utricle involving the vasa is a rare
      presentation.

PMID- 15977603
TI  - Urethral reconstruction using buccal mucosa urethroplasty in the treatment of
      urethral injury.
AB  - A 52-year-old Japanese man was referred to us with a urethral injury caused by
      masturbation. His penis was swollen and about one and a half times its size due
      to urine extravasation and infection. Foreign bodies were surgically removed, and
      debridement and excision of necrotic tissue were performed. After confirming that
      the infection was under control, we planned the reconstruction of the urethra and
      penis, following endoscopic urethrotomy for the bulbous urethra stricture. A free
      graft from the buccal mucosa was harvested, placed over the defect and fixed with
      interrupted suture as ventral onlay. The patient could achieve satisfactory
      voiding and no complication was seen during the 18-month follow up. In our
      experience, buccal mucosa is a useful source of urethral grafting material and
      excellent results can be expected in case of urethral injury.

PMID- 15977604
TI  - [Spermatic cord tuberculosis: a case report].
AB  - A 65-year-old man visited our hospital with a complaint of a left inguinal mass.
      He had had a past history of tuberculosis. A left spermatic cord tumor was
      suspected. Left high orchiectomy was performed. The mass did not connect with the
      testis or epididymis. The removed mass measured 4 x 2 x 1.5 cm in size.
      Microscopic examination showed a granulomatous lesion with Langhans giant cells.
      Tuberculin skin test was moderately positive. From these findings we diagnosed
      the patient with tuberculosis in spermatic cord. Antituberculous chemotherapy was
      subsequently initiated. Two months after surgery, recurrence has not been found.

PMID- 15977605
TI  - Avian influenza ravages Thai tigers.

PMID- 15977606
TI  - Wildlife champion recognised as animal welfare hero.

PMID- 15977607
TI  - The federal election aftermath--what does it mean for the AVA?

PMID- 15977608
TI  - The Mulesing debate.

PMID- 15977610
TI  - Classical swine fever--a step closer.

PMID- 15977609
TI  - Prescribing and dispensing--could this happen to you?

PMID- 15977611
TI  - Treatment of eight dogs with nasal tumours with alternating doses of doxorubicin
      and carboplatin in conjunction with oral piroxicam.
AB  - OBJECTIVE: To determine the efficacy and toxicity of chemotherapy in the
      treatment of canine nasal tumours. DESIGN: Retrospective clinical study
      PROCEDURE: Eight dogs with histologically confirmed nasal tumours were staged by
      means of complete blood count, serum biochemical analysis, cytological analysis
      of fine needle aspirate of the regional lymph nodes, thoracic radiographs and
      computed tomography scan of the nasal cavity. All dogs were treated with
      alternating doses of doxorubicin, carboplatin and oral piroxicam. All dogs were
      monitored for side effects of chemotherapy and evaluated for response to
      treatment by computed tomography scan of the nasal cavity after the first four
      treatments. RESULTS: Complete remission was achieved in four dogs, partial
      remission occurred in two dogs and two had stable disease on the basis of
      computed tomography evaluation. There was resolution of clinical signs after one
      to two doses of chemotherapy in all dogs. CONCLUSIONS: This chemotherapy protocol
      was efficacious and well tolerated in this series of eight cases of canine nasal
      tumours.

PMID- 15977612
TI  - Efficacy of cyclosporin in the treatment of atopic dermatitis in dogs--combined
      results from two veterinary dermatology referral centres.
AB  - OBJECTIVE: To evaluate the efficacy of cyclosporin in controlling the clinical
      signs associated with atopic dermatitis in dogs under Australian field
      conditions. DESIGN: A multicentre prospective clinical investigation of the use
      of cyclosporin in 41 dogs with atopic dermatitis. PROCEDURE: Dogs were treated
      with cyclosporin (5 mg/kg orally once daily with food) for 6 weeks. Four clinical
      parameters of severity of atopic dermatitis were measured on Day 0 and on Day 42
      using a 0 to 4 scoring system. Individual variables were then combined to form a
      Global Score. Both client and clinician observed pruritus scores were combined to
      form a Pruritus Score. Pre- and post-treatment scores were statistically
      analysed. The difference in results between the two investigators was also
      recorded and analysed. RESULTS: All dogs showed a marked reduction in pruritus
      and erythema during the 6-week treatment period. All dogs showed a significant (P
      < 0.001) improvement in clinical lesion scores and Global Score (P < 0.001). The
      mean percentage improvement in Global Score from Day 0 to Day 42 was 83.9%. The
      mean percentage improvement in Pruritus Score from Day 0 to Day 42 was 83%. The
      medication was well tolerated. Side effects such as vomiting, diarrhoea and soft
      stools were observed in four dogs. Another four dogs developed bacterial pyoderma
      during the trial period. There was no significant difference in results between
      the two centres. CONCLUSION: Cyclosporin was well tolerated and efficacious in
      the symptomatic treatment of atopic dermatitis in dogs attending two veterinary
      dermatology referral centres in Australia, under Australian field conditions,
      when administered at 5 mg/kg/day for 6 weeks.

PMID- 15977613
TI  - Successful treatment of cryptococcal pneumonia in a pony mare.
AB  - A 20-year-old Welsh Mountain Pony (212 kg) mare was initially presented for a
      chronic cough, fever, weight loss and low grade abdominal pain. She later
      developed dyspnoea, tachypnoea and exercise intolerance. The presence of multiple
      masses (up to 17 cm diameter) in the pulmonary parenchyma was established using
      lateral thoracic radiography and transthoracic ultrasonography. Encapsulated,
      budding yeasts were observed in smears made from transtracheal washings and
      needle aspirates of the pulmonary lesions. Cryptococcus gattii (synonym:
      Cryptococcus neoformans variety gattii; Cryptococcus bacillisporus) was cultured
      from the transtracheal washings and aspirates of the lung masses. The pony was
      successfully treated using daily intravenous infusions of amphotericin B
      (typically 0.5 mg/kg in 1 L 5% dextrose in water over 1 h, following
      premedication with 50 mg flunixin intravenously) over a 1 month period, until a
      cumulative dose of 3 g had been administered. Treatment was considered to be
      successful on the basis of progressive improvement in clinical signs, reduction
      in the size of pulmonary cryptococcomas, 48 kg weight gain and a reduction in the
      cryptococcal antigen titre from 4096 to 256, 1 year after cessation of treatment.

PMID- 15977614
TI  - Critical reviews and evidence-based medicine.

PMID- 15977615
TI  - Is Chlamydophila felis a significant zoonotic pathogen?
AB  - PROBLEM: Chlamydophila felis is a common cause of conjunctivitis in cats and in
      some textbooks is listed as an important zoonotic pathogen. However, there are no
      published comprehensive reviews assessing the evidence supporting this. SEARCH
      AND ANALYSIS: Bibliographic databases and bibliographies of papers and textbooks
      were searched for all published cases of zoonotic disease associated with
      chlamydiosis in cats. All published case reports were reviewed to establish the
      quality of the evidence supporting the association between C. felis and zoonotic
      disease. RESULTS: There are only seven case reports, most of which were published
      before the development of assays capable of distinguishing C. felis from other
      chlamydial species, implicating this organism in zoonotic disease. None of the
      three cases of pneumonia and systemic disease described, two of which occurred in
      immunocompromised patients, can be unambiguously attributed to C. felis. Of the
      four cases of follicular keratoconjunctivitis described, only one, in an
      immunocompromised patient, could be unambiguously attributed to C. felis.
      CONCLUSION: While there is evidence that C. felis may occasionally cause
      keratoconjunctivitis in humans, there is little evidence to suggest it can cause
      serious systemic disease or pneumonia.

PMID- 15977616
TI  - Behavioural responses of calves to amputation dehorning with and without local
      anaesthesia.
AB  - OBJECTIVE: To assess the pain elicited by amputation dehorning and evaluate the
      effect of local anaesthesia by using changes in calf behaviour. METHODS: The
      behaviour of 6-month-old Friesian calves (n = 60), subjected to control handling,
      dehorned or dehorned after local anaesthesia treatment, was monitored in this
      study. The proportion of calves displaying particular behaviours was recorded
      using instantaneous scan sampling during the first 10 h and between 26 and 29 h
      after treatment. RESULTS: The three behaviours of tail flicking, head shaking and
      ear flicking displayed similar features with time according to treatment and
      appeared to occur in an inverse relation to rumination. Dehorned calves were
      highly restless for the first 6 h after treatment. A significantly greater
      proportion of them displayed tail flicking, head shaking and ear flicking than
      the control calves, which, by contrast, stood still and ruminated (P < 0.05). The
      behaviour of calves given local anaesthetic prior to dehorning was similar to
      that of the control calves for the first 2 h. Thereafter the proportion of calves
      displaying tail flicking, head shaking and ear flicking increased, rumination
      decreased, and the behaviour was similar to that of the dehorned calves.
      CONCLUSIONS: These results suggest that dehorning is a painful experience that
      lasts about 6 h and that local anaesthetic alleviates that pain during its period
      of action. It is recommended that local anaesthetic be administered when
      conducting amputation dehorning.

PMID- 15977617
TI  - Detection of subgroup J avian leukosis virus infection in Australian meat-type
      chickens.
AB  - OBJECTIVE: To determine the extent of avian leukosis virus subgroup J (ALV-J)
      infection in Australian broiler breeder flocks, using virus isolation and
      molecular biological detection. Any resultant ALV-J viral isolates to be
      characterised by neutralisation cross testing in order to determine antigenic
      relationships to overseas isolates of ALV-J. STUDY DESIGN: Samples of blood,
      feather pulp, albumen and tumours were obtained from broiler breeder flocks which
      represented four genetic strains of meat chickens being grown in Victoria, South
      Australia, NSW and Queensland. Dead and ailing birds were necropsied on farm and
      samples were collected for microscopic and virological examinations. Virus
      isolation was carried out in C/O and DF-1 CEF cultures and ALV group specific
      antigen was detected in culture lysates using AC-ELISA. Micro-neutralisation
      assay was used for antigenic characterisation of selected isolates. Genomic DNA
      was isolated from cultured cells, tumours and feather pulp. ALV-J envelope
      sequences were amplified by PCR using specific ALV-J primers while antibodies
      against ALV-J were detected by ELISA. RESULTS: A total of 62 ALV-J isolates were
      recovered and confirmed by PCR from 15 (31.3%) of 48 breeder flocks tested.
      Antibody to ALV-J was detected in 20 (47.6%) of the 42 flocks tested.
      Characteristic lesions of myeloid leukosis caused by ALV-J were found in affected
      flocks. The gross pathological lesions were characterised by skeletal
      myelocytomas located on the inner sternum and ribs, neoplastic enlargement of the
      liver, and in some cases gross tumour involvement of the spleen, kidney, trachea,
      skeletal muscles, bone marrow, skin and gonads. Microscopically, the tumours
      consisted of immature granulated myelocytes, and were present as focal or diffuse
      infiltrations in the affected organs. Virus micro-neutralisation assays
      demonstrated antigenic variation among Australian isolates and to overseas
      strains of ALV-J. CONCLUSION: ALV-J infection was prevalent in Australian broiler
      breeder flocks during 2001 to 2003. Australian isolates of ALV-J show a degree of
      antigenic variation when compared to overseas isolates.

PMID- 15977618
TI  - Reassessment of the toxicity of Hypericum perforatum (St John's wort) for cattle.
AB  - OBJECTIVE: To investigate the clinical effect of administering sufficient
      Hypericum perforatum to cattle to deliver quadruple the reported oral toxic dose.
      ANIMALS: Thirty-six yearling Hereford (n = 18) and Angus (n = 18) steers. DESIGN:
      A series of six experiments was conducted, each using 12 animals in a 2 x 2
      factorial design, with two breeds of cattle (Hereford, Angus) and two dose levels
      of hypericin, 1.5 mg/kg (treated group) and 0 mg/kg (control group). Each set of
      12 steers was used in duplicate experiments, with all animals alternated between
      treated and control groups. PROCEDURES: Treated groups received finely milled H.
      perforatum administered orally in gelatin capsules to provide 1.5 mg hypericin/kg
      body weight. All cattle were then exposed to direct sunlight for 5 h per day for
      5 successive days. Rectal temperatures were measured immediately before and at
      the end of each sunlight exposure session. Rectal temperature above 40 degrees C,
      together with some other clinical sign of hypericin poisoning, was considered
      indicative of intoxication. RESULTS: No animals developed a rectal temperature
      above 40 degrees C or other clinical signs of hypericin poisoning. CONCLUSIONS:
      While the reported bovine oral toxic dose of 3 g dried plant/kg body weight, for
      flowering stage, presumed narrow leaved biotype, H. perforatum, is probably
      correct, the corresponding dose for hypericin of 0.37 mg/kg is incorrect. Based
      on its known concentration in this plant the toxic dose of hypericin for
      partially pigmented Hereford-cross cattle is estimated at about 10.5 mg/kg body
      weight and more than this for fully pigmented cattle. This would imply that
      cattle of the former type should be about three and a half times better protected
      against H. perforatum toxicity than are unpigmented, wool protected, Merino
      sheep. Cattle, particularly if fully pigmented, may have a role in grazing
      management to control H. perforatum.

PMID- 15977620
TI  - The role of wild aquatic birds in the epidemiology of avian influenza in
      Australia.

PMID- 15977621
TI  - [Prevention--doping--heart groups. Sports medicine is more than pulse and blood
      pressure monitoring].

PMID- 15977619
TI  - Coccidiosis and sudden death in an adult alpaca (Lama pacos).

PMID- 15977622
TI  - [L-dopa effectiveness decreases over time. What helps Parkinson patients stay
      mobile?].

PMID- 15977623
TI  - [Depressive syndrome, psychoses, dementia: frequent manifestations in Parkinson
      disease].

PMID- 15977624
TI  - [American Hypertension Society (ASH) on the offensive. Hypertension without high
      blood pressure?].

PMID- 15977625
TI  - [Nature lovers--a meal for tics].

PMID- 15977626
TI  - [Cost saving program instead of optimizing therapy: disease mismanagement in
      diabetes mellitus? (interview by Dr. med. Jochen Aumiller)].

PMID- 15977627
TI  - [Patients should have the right to die with dignity and free from pain. Caring
      for your patients to the end].

PMID- 15977628
TI  - [How you can ease the suffering of the dying patient].
AB  - Taking care of the dying is an important and demanding concern for the general
      physician. In addition to the amelioration of pain, he also has to help the
      patient to cope with dyspnea, vomiting, constipation, depression and anxiety. To
      this end, not only morphine but also anti-emetic drugs, laxatives and peristalsis
      stimulating suppositories, benzodiazepines and neuroleptics with a sedating
      effect can make it easier for the patient during the terminal phase of his life.
      As least as important as the support provided by medication, however, are
      sympathetic communication with the patient and human warmth.

PMID- 15977629
TI  - [Pain therapy in cancer patients].
AB  - Rigorous and appropriate pain therapy is a major element in palliative medicine,
      and affords the patient the possibility of being better able to organize the
      remaining time left to him. Every person has a legal right to, receive
      appropriate treatment for his/her pain, which in advanced disease states, is a
      multidimensional condition. This means that in addition to nursing staff and
      physicians, spiritual counselors, social workers, physiotherapists and volunteer
      helpers must be included in the pain-management team. Despite all our efforts,
      the ideal of complete freedom from pain is unrealistic. Nevertheless, the simple
      expression of solidarity with the terminally-ill patient, as is reflected by the
      provision of sympathetic attention, has in itself a positive impact on pain. By
      offering comprehensive and nationwide palliative care that is oriented to the
      needs of the terminal patient, society helps to provide a culture of the dying,
      and thus also of the living, that reflects humanistic principles.

PMID- 15977630
TI  - [A family physician and a clergyman report on their daily routines. What now when
      medical measures have been exhausted?].

PMID- 15977631
TI  - [Anti-phospholipid antibody syndrome: a case report (interview by Dr. Erik
      Heintz)].
AB  - In a 29-year old patient with a triad of symptoms arising from an abortion in
      conjunction with a thrombosis and thrombocytopenia, the suspicion of an anti
      phospholipid antibody syndrome (APS) was confirmed through the detection of
      increased levels of antiphospholipid antibody. Because of the continued wish to
      have children, the patient received oral methyl prednisolone and therapeutic
      doses of low molecular weight heparin.

PMID- 15977634
TI  - [New trend in asthma therapy. Already early administration of inhaled corticoids-
      but low dosage when possible for long-term treatment].

PMID- 15977632
TI  - [Main symptom otorrhea: diagnosis and therapy].
AB  - Otorrhea is an ambiguous symptom that underlies diverse clinical pictures.
      Fundamentally, the treatment of uncomplicated acute otitis externa and media can
      be carried out by the family physician. An ENT specialist should be definitely
      consulted in cases of complications or development of a chronic condition.

PMID- 15977635
TI  - [Patients profit from "on site activation". Ciclesonide first becomes active in
      the lung].

PMID- 15977633
TI  - [A shock for 348 colleagues. Penalties up to 400,000 euro].

PMID- 15977636
TI  - [Initial results of the PROTECT Study publicized. Stroke patients need effective
      thrombosis prevention].

PMID- 15977637
TI  - [Marcumarized patient must have surgery. Playing it safe with low molecular
      weight heparin bridging].

PMID- 15977638
TI  - [Pseudoacanthosis nigricans].

PMID- 15977639
TI  - Population-based studies on incidence, survival rates, and genetic alterations in
      astrocytic and oligodendroglial gliomas.
AB  - Published data on prognostic and predictive factors in patients with gliomas are
      largely based on clinical trials and hospital-based studies. This review
      summarizes data on incidence rates, survival, and genetic alterations from
      population-based studies of astrocytic and oligodendrogliomas that were carried
      out in the Canton of Zurich, Switzerland (approximately 1.16 million
      inhabitants). A total of 987 cases were diagnosed between 1980 and 1994 and
      patients were followed up at least until 1999. While survival rates for pilocytic
      astrocytomas were excellent (96% at 10 years), the prognosis of diffusely
      infiltrating gliomas was poorer, with median survival times (MST) of 5.6 years
      for low-grade astrocytoma WHO grade II, 1.6 years for anaplastic astrocytoma
      grade III, and 0.4 years for glioblastoma. For oligodendrogliomas the MSTwas 11.6
      years for grade II and 3.5 years for grade III. TP53 mutations were most frequent
      in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and
      oligoastrocytomas (44%), but infrequent (13%) in oligodendrogliomas. LOH 1p/19q
      typically occurred in tumors without TP53 mutations and were most frequent in
      oligodendrogliomas (69%), followed by oligoastrocytomas (45%), but were rare in
      fibrillary astrocytomas (7%) and absent in gemistocytic astrocytomas.
      Glioblastomas were most frequent (3.55 cases per 100,000 persons per year)
      adjusted to the European Standard Population, amounting to 69% of total incident
      cases. Observed survival rates were 42.4% at 6 months, 17.7% at one year, and
      3.3% at 2 years. For all age groups, survival was inversely correlated with age,
      ranging from an MST of 8.8 months (<50 years) to 1.6 months (>80 years). In
      glioblastomas, LOH 10q was the most frequent genetic alteration (69%), followed
      by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and
      PTEN mutations (24%). LOH 10q occurred in association with any of the other
      genetic alterations, and was the only alteration associated with shorter survival
      of glioblastoma patients. Primary (de novo) glioblastomas prevailed (95%), while
      secondary glioblastomas that progressed from low-grade or anaplastic gliomas were
      rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%)
      and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57%
      were in hot-spot codons 248 and 273, while in primary glioblastomas, mutations
      were more evenly distributed. G:C-->A:T mutations at CpG sites were more frequent
      in secondary than primary glioblastomas, suggesting that the acquisition of TP53
      mutations in these glioblastoma subtypes may occur through different mechanisms.

PMID- 15977640
TI  - Molecular regulation of acute ethanol-induced neuron apoptosis.
AB  - Ethanol is a potent neurotoxin particularly for the developing nervous system.
      Intrauterine exposure to ethanol during the last trimester of human gestation can
      produce a broad spectrum of neuropathologic consequences. This period of human
      brain development is roughly equivalent to the first week of rodent postnatal
      life and acute exposure of neonatal mice to ethanol produces massive neuronal
      apoptosis throughout the brain. We have previously demonstrated that ethanol
      induced neuron apoptosis is critically dependent on expression of Bax, a
      proapoptotic member of the Bcl-2 family. To further define the molecular pathway
      regulating ethanol-induced neuron apoptosis, we analyzed the effects of acute
      ethanol exposure on cerebellar internal granule cell neurons both in vivo and in
      vitro. Ethanol produced extensive Bax-dependent caspase-3 activation and neuron
      apoptosis in the cerebellar internal granule cell layer, which was maximal at
      approximately 6 hours postadministration. This effect was recapitulated in vitro
      and required new gene transcription, protein translation, Bax expression, and
      caspase activation. Ethanol-induced neuron death was independent of p53
      expression and was unaffected by deficiency in the proapoptotic Bcl-2 family
      members Bid or Bad. These studies indicate that ethanol activates an intrinsic
      apoptotic death program in neurons that is likely to contribute to the
      neuropathologic effects of human fetal alcohol exposure.

PMID- 15977641
TI  - HIV-1 gp120 proteins alter tight junction protein expression and brain
      endothelial cell permeability: implications for the pathogenesis of HIV
      associated dementia.
AB  - Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV
      associated dementia (HAD) despite the lack of productive infection of the brain
      endothelium. It is likely that secreted viral products play a major role in BBB
      damage and the development of HAD. The objective of this study is to determine
      the effects of gp120 proteins on brain endothelial cell permeability and
      junctional protein expression. Our results showed that treatment of cultured
      human brain endothelial cells with gp120 for 24 hours results in increased
      permeability of the endothelial monolayer. Also, gp120 proteins caused disruption
      and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in
      these cells. Other junctional proteins such as claudin-1 and claudin-5 were
      unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins
      alter both the functional and molecular properties of the BBB, which could
      increase trafficking of HIV, infected cells, and toxic humoral factors into the
      central nervous system and contribute to the pathogenesis of HAD.

PMID- 15977642
TI  - Visualization of Central European tick-borne encephalitis infection in fatal
      human cases.
AB  - Central European tick-borne encephalitis (TBE) is caused by a flavivirus vectored
      by the Ixodes ricinus tick. In severe infections, TBE presents as
      (myelo)meningoencephalitis with considerable mortality. Characteristic
      neuropathologic changes feature a multinodular to patchy polioencephalomyelitis
      accentuated in spinal cord, brainstem, and cerebellum. Visualization of viral
      infection by immunohistochemistry has not yet been achieved. We analyzed
      immunohistochemically the distribution of viral antigens and its correlation with
      neuropathologic changes, serological data, and disease duration in 28 brains of
      cases with a clinical diagnosis of TBE and neuropathologically confirmed
      (meningo)encephalomyelitis. In 20 brains (including 10 seropositives), viral
      antigens were detectable. These cases were characterized by relatively short
      clinical duration ranging from 4 to 35 days. Immunoreactivity was most prominent
      in perikarya and processes of Purkinje cells and large neurons of dentate
      nucleus, inferior olives, and anterior horns. In addition, immunoreactivity was
      detected in neurons of other brainstem nuclei, isocortex, and basal ganglia.
      There was an inverse topographical association of severe inflammatory changes
      with presence of viral antigens. Some cytotoxic T cells were in direct contact
      with tick-borne encephalitis virus (TBEV)-infected neurons. We conclude that 1)
      TBE viral antigens are immunohistochemically detectable in brains of fatal cases
      with relatively short natural clinical course; 2) TBE virus neurotropism
      preferentially targets large neurons of anterior horns, medulla oblongata, pons,
      dentate nucleus, Purkinje cells, and striatum; 3) topographical correlation
      between inflammatory changes and distribution of viral antigens is poor; and 4)
      immunologic mechanisms may contribute to nerve cell destruction in human TBE.

PMID- 15977643
TI  - Autophagic vacuoles with sarcolemmal features delineate Danon disease and related
      myopathies.
AB  - Among the autophagic vacuolar myopathies (AVMs), a subgroup is characterized
      pathologically by unusual autophagic vacuoles with sarcolemmal features (AVSF)
      and includes Danon disease and X-linked myopathy with excessive autophagy. The
      diagnostic importance and detailed morphologic features of AVSF in different AVMs
      have not been well established, and the mechanism of AVSF formation is not known.
      To address these issues, we have performed detailed histologic studies of
      myopathies with AVSF and other AVMs. In Danon disease and related AVMs, at the
      light microscopic level, autophagic vacuoles appeared to be accumulations of
      lysosomes, which, by electron microscopy consisted of clusters of autophagic
      vacuoles, indicative of autolysosomes. Some autolysosomes were surrounded by
      membranes with sarcolemmal proteins, acetylcholinesterase activity, and basal
      lamina. In Danon disease, the number of fibers with AVSF increased linearly with
      age while the number with autolysosomal accumulations decreased slightly,
      suggesting that AVSF are produced secondarily in response to autolysosomes. Most
      of the AVSF form enclosed spaces, indicating that the vacuolar membranes may be
      formed in situ rather than through sarcolemmal indentation. This unique
      intracytoplasmic membrane structure was not found in other AVMs. In conclusion,
      AVSF with acetylcholinesterase activity are autolysosomes surrounded by
      secondarily generated intracytoplasmic sarcolemma-like structure and delineates a
      subgroup of AVMs.

PMID- 15977644
TI  - HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro:
      implications for immune escape in vivo.
AB  - The nonclassical MHC class I molecule HLA-E is the only known ligand for
      CD94/NKG2A and CD94/NKG2C expressed on NK and CD8+ alphabeta and gammadelta T
      cells. HLA-E may transmit either activating signals via CD94/NKG2C or inhibitory
      signals mediated by CD94/NKG2A. Here we show that HLA-E is expressed at mRNA and
      protein level in human long-term glioma cell lines, primary ex vivo polyclonal
      glioblastoma cell cultures and surgical glioblastoma specimens. Furthermore,
      immunohistochemistry revealed an enhanced in vivo expression of HLA-E in gliomas
      of lower grades and a massive overexpression in grade IV glioblastomas compared
      with normal CNS tissue. An immune-inhibitory effect of HLA-E on tumor-specific
      CTL has already been described. We show that siRNA-mediated silencing of HLA-E or
      blocking of CD94/NKG2A enables NKG2D-mediated lysis of 51Cr-labeled tumor cells
      by NK cells. Thus, our study provides the first evidence that expression and
      interaction of HLA-E on cancer cells with CD94/NKG2A expressed on lymphocytes
      compromises innate anti-tumor immune responses.

PMID- 15977645
TI  - Influence of HAART on HIV-related CNS disease and neuroinflammation.
AB  - Neuroinflammation has an established link with AIDS-related dementia but has not
      been investigated in the post-highly active anti-retroviral therapy (HAART) era.
      In this autopsy study we examined post-HAART cases in Edinburgh for the presence
      of HIV-related pathology and in well-treated cases for evidence of
      neuroinflammation. We focused on basal ganglia and the hippocampus, 2 key areas
      of the brain for cognitive functioning and compared pre- and post-HAART cases for
      neuroinflammatory status. We find evidence, post-HAART, that there is a high
      level of microglial/macrophage activation that is comparable with the levels
      seen, pre-HAART, in HIV encephalitis (HIVE) and AIDS cases. This result was
      maximal in the hippocampus where microglial/macrophage upregulation in the HAART
      treated group exceeded that seen in HIVE. In the basal ganglia, HAART-treated
      cases showed significantly higher levels of CD68-positive microglia/macrophages
      than in control brains (p = 0.004), and in the hippocampus levels were
      significantly higher than those seen in control cases, pre-HAART AIDS, and
      presymptomatic brains (p = 0.01). However, lymphocyte levels in the areas
      examined were low in HAART-treated cases. We conclude that there is a surprising
      degree of ongoing neuroinflammation in HAART-treated patients, particularly in
      the hippocampus. This may pose a threat for the future health of individuals
      maintained long-term on HAART therapy.

PMID- 15977646
TI  - Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex
      of Mecp2-deficient mice.
AB  - We detected morphologic abnormalities in the cerebral cortex of Mecp2-hemizygous
      (Mecp2(-/y)) mice. The cortical thickness of both somatosensory and motor
      cortices in mutants did not increase after 4 weeks of age, as compared with that
      in wild-type male mice. The density of neurons in those areas was significantly
      higher in layers II/III and V of Mecp2(-/y) mice than in wild-type mice,
      particularly in layers II/ III after 4 weeks of age. In layer II/III of the
      somatosensory cortex of Mecp2(-/y) mice, the diameter of the apical dendrite was
      thin and the number of dendritic spines was small. Electron microscopy revealed
      that two-week-old mutants already had numerous premature postsynaptic densities.
      These results indicate that Mecp2(-/y) mice suffered delayed neuronal maturation
      of the cerebral cortex and that the initial neuronal changes were caused by
      premature synaptogenesis. Rett syndrome patients with a heterozygous mutation of
      Mecp2 display developmental disorders including cortical malfunctions such as
      mental retardation, autism, and epilepsy. Our results provide evidence of the
      similarity with Rett syndrome brains in some respects and suggest that
      MeCP2/Mecp2 plays some role in synaptogenesis.

PMID- 15977647
TI  - Neuronal intranuclear inclusion disease without polyglutamine inclusions in a
      child.
AB  - Neuronal intranuclear inclusion disease (NIID) is a rare and heterogeneous group
      of slowly progressive neurodegenerative disorders characterized by the widespread
      presence of eosinophilic neuronal intranuclear inclusions (NII) accompanied by a
      more restricted pattern of neuronal loss. We report here the pathologic findings
      in a 13-year-old boy who died after a 6-year clinical history of progressive
      ataxia, extrapyramidal manifestations, and lower motor neuron abnormalities.
      Histological evaluation of the brain revealed widespread NII in most neurons.
      Marked loss of cerebellar Purkinje cells and neurons in the dentate nucleus, red
      nucleus, and spinal cord anterior horns was accompanied by a modest astrocytosis.
      Because of the abundance of NII and the absence of a relationship between NII and
      neuronal loss or microglial activation, we conclude that loss of cerebellar,
      brainstem, and spinal cord neurons reflects selective neuronal vulnerability. NII
      were immunoreactive for ubiquitin, glucocorticoid receptor, and SUMO-1, a small,
      ubiquitin-like protein purportedly involved in protein transport and gene
      transcription. NII were non-reactive for polyglutamine (1C2), TATA binding
      protein, promyelocytic leukemia protein, heat shock protein 90, tau, alpha
      synuclein, neurofilament, and beta amyloid. The moderate ubiquitin and strong
      SUMO-1 staining of NII in juvenile cases is the reverse of the pattern noted in
      adult diseases, suggesting the two age groups are pathogenically distinct. We
      suggest that juvenile NIID is a spinocerebellar brainstem ataxic disease possibly
      related to an abnormality in SUMOylation.

PMID- 15977648
TI  - Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer
      disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA).

PMID- 15977649
TI  - [Serum concentration of some tumor markers in renal failure].
AB  - This study was undertaken to define the relationship between renal function and
      the blood level of some tumor markers. In order to evaluate the specificity of
      tumor markers in cronic renal failure the following alphaFP, CEA, NSE, SCC and
      beta2 microglobulin were studied in 40 adult patients, with cronic renal failure
      of different degrees (27 p.), in hemodialyzed patients (6 p.) and in 7 healthy
      volunteers who did not present any clinical symptoms or signs of neoplasia. The
      decrease in glomerular filtration rate (GFR) was accompanied by an increase in
      serum levels of CEA, SCC and beta2 microglobulin. The serum level of CEA, SCC
      increased gradually when GFR fell below 75 ml/min. The serum level of beta2
      microglobulin increased when GFR fall below 30 ml/min. Serum level of CEA, SCC
      and beta2 microglobulin was found to be increased in hemodialyzed patients. In
      conclusion in cronic renal failure and in hemodialyzed patients some tumor
      markers (CEA, SCC and beta2 microglobulin) show a high false positive rate and
      may be unreliable for monitoring malignancies in uremic patients, while alphaFP
      and NSE appear to maintain their specificity.

PMID- 15977650
TI  - [Accuracy of the cytopathological telediagnosis of palpable limphoadenopathies. A
      study design simulating the diagnostic support from remote access to health
      workers in the developing countries].
AB  - It has been estimated the accuracy of the cytologic diagnosis, carried out by a
      cytopathologist, on digital images (DID) of fine needle aspiration lymphonode
      biopsies (FNAB), in order to validate the telematic support to health workers
      practising in specialist-lacking remote areas of the developing countries. A
      blind-cross check simulation design was drawn-up. A non-pathologist practictioner
      selected the microscopic fields of 39 cases of FNAB, took the pictures with a
      digital camera, stored them and submitted to a cytopathologist for DID. The DID
      were compared against the original diagnosis in direct view (DVC). The histologic
      diagnosis on the surgical biopsies were the golden standard to refer to. The
      results demonstrate that: 1) DVC and DID have similar and satisfactory
      sensitivity rates (88.2 e 85.3%) and positive predictive values (96.8 e 90.1%);
      2) DID have lower specificity and efficiency rates against DVC (40.0 vs 80.0 and
      79.5 vs 79.2%); 3) the negative predictive values are low both in DVC and DID
      (50.0 e 28.6%), but the data ought to be confirmed in a well-balanced ratio
      malignancy-benignancy; d) the accuracy of DID could be increased by improving the
      selection process of the microscopic fields; e) the remote access-assisted
      cytologic diagnosis of FNAB can be a procedure to carry out easily and cheaply in
      areas where the histopathology facilities are unavailable. The accuracy is the
      highest in metastasis, in high-grade non-Hodgkin lymphoma and in lymphocite
      depletion and mixed cell sub-groups of Hodgkin lymphoma.

PMID- 15977651
TI  - [GPs' self-perception of their own role compared with hospital, ambulatory,
      academic, and health organisation physicians].
AB  - Aim of the present study was to explore how the 76 general practitioners (GPs) -
      serving Carpi district (90,000 residents) - value their own role compared with
      the hospital, ambulatory, academic, and health organisation physicians'. GPs had
      a positive self-image only in comparison with health organisation doctors (7 vs 7
      grades). GPs disappointed with themselves when comparing their role with
      ambulatory (-1.6 grades), academic (-1.9 grades) and hospital doctors (-2.2
      grades). Secondarily, GPs perceived patients' valuing their professional role
      mostly 'subordinate' to the other physicians', except health organisation
      colleagues'.

PMID- 15977652
TI  - [Chemotherapy in extended small-cell lung cancer. Retrospective analysis of two
      different series of patients treated with carboplatin and etoposide or
      ciclophosphamide-epidoxorubicin and etoposide].
AB  - Although cisplatin and etoposide seem to represent the treatment of choice in
      Small-Cell Lung Cancer, a lot of data exist in literature supporting both the use
      of anthracycline-containing regimens and the use of alternating regimens where
      platinum-containing regimens and anthracycline-containing regimens are
      alternatively used as first line in the same patient. In our paper we review the
      outcomes of two different series of patients treated with ciclophosphamide
      epidoxorubicin-etoposide (CEVP16) or carboplatin-etoposide (CBE) for extended
      Small-Cell Lung Cancer. Sixty-three patients (53.4%) were treated with CEVP16 and
      55 patients (46.6%) with CBE. Response Rate (complete plus partial responses) was
      greater in patients treated with CEVP16 (49.2%) when compared with the response
      rate in patients treated with CBE (30.9%) (p=0.04 using the Chi-Square test); no
      differences were observed in the median time to progression (235 vs 199 days,
      using the Log-Rank test). Overall survival was greater in the CEVP16 group when
      compared with the CBE one (281 vs 208 days and 35.6% vs 16.3% of patients alive
      after 2 years of follow up for CEVP16 and CBE respectively, p=0.02 using the Log
      Rank test). Although our data present all the methodological limits of the "case
      series", it is interesting to observe how an anthracycline-containing regimen
      seems to be more effective than a platinum-containing one and how it could still
      play a role in the treatment of extended Small-Cell Lung Cancer.

PMID- 15977653
TI  - [Focal nodular hyperplasia of the liver. A case report].
AB  - Focal nodular hyperplasia (FNH) of the liver is a benign disorder that usually
      occurs in women during their reproductive years. Multiple FNH is very rare. A
      case of multiple FNH of the liver occurring in a 34-year-old woman is described.
      FNH diagnosis was confirmed by means of US, CT, MR, scintigraphy and hepatic
      biopsy. There was no further change in either size or appearance of liver masses
      in the ensuing 6 years of follow-up.

PMID- 15977654
TI  - [Genome and infectious diseases].
AB  - Infectious diseases are a leading cause of death worldwide. This century has seen
      a remarkable increase of new infectious diseases and the re-emergence of old
      ones. This paper gives an overview on the innovative strategies and new
      technology platforms needed to counteract the novel emerging diseases.

PMID- 15977655
TI  - [Freedom to get fat?].

PMID- 15977656
TI  - [Scientific iconography: requirements and limits].

PMID- 15977657
TI  - [Autoimmune thrombocytopenia: diagnosis and treatment].
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized
      by an isolated, persistent thrombocytopenia in absence of known causes. In this
      review, we briefly analyze the most important diagnostic criteria of this
      autoimmune disorder, with particular consideration to differential diagnosis
      (false thrombocytopenia, congenital thrombocytopenia, acquired thrombocytopenia,
      pregnancy-associated thrombocytopenia) and to therapeutic options.

PMID- 15977658
TI  - [Osteoporotic risk in Crohn's disease].
AB  - The pathogenetic mechanisms, risk factors and relationship between densitometric
      data and risk of fractures have been examined. The results of treatment trials
      and prevention measures have been showed.

PMID- 15977659
TI  - [How much? For how long?].

PMID- 15977660
TI  - [John Paul II. The Pope who put health in the first place].

PMID- 15977662
TI  - [Overview of conversion disorders].

PMID- 15977663
TI  - [Humanization in health].

PMID- 15977664
TI  - [Emergency: hypercalcemia --when serum K+ is not good].

PMID- 15977661
TI  - [Depression in diabetics].

PMID- 15977665
TI  - [Informed consent in pediatrics].

PMID- 15977666
TI  - [Role of calcium in nutrition balance and disease prevention].

PMID- 15977667
TI  - [Physical burden in the nursing profession --risk or reality?].

PMID- 15977668
TI  - [Visit to an elderly home].

PMID- 15977669
TI  - [Trip to Tunisia].

PMID- 15977670
TI  - Connecting the industry. HHS outlines details for national IT network.

PMID- 15977671
TI  - Hatch hunts for hospitals. Minnesota is now the main stage in U.S. debate over
      uninsured billing as a third group of hospitals sign pacts with state officials.
AB  - Minnesota has become the main stage in the debate over uninsured billing. Forthe
      third month in a row, state authorities have signed agreements with hospitals to
      expand discount programs and limit debt-collection efforts. The latest deal means
      about 75% of admissions there will be covered by such pacts. "We saw this as a
      positive response to a major public challenge," said Terence Pladson, left, of
      CentraCare.

PMID- 15977672
TI  - Wary physicians. Defensive medicine linked to higher costs, less access.

PMID- 15977673
TI  - Protective moves. Caps may lure docs to rural communities: study.

PMID- 15977674
TI  - Not enough detail. HHS' tech efforts need more planning, goals: GAO.

PMID- 15977675
TI  - After the moratorium. Battle over specialty hospitals shifts to Congress.

PMID- 15977676
TI  - Round 2 under way for Tenet.

PMID- 15977677
TI  - Heads firmly in the sand. Industry fails to get in the game of health system
      change.

PMID- 15977679
TI  - Seeking compatibility. Certification proposed for EHRs in diabetes cases.

PMID- 15977678
TI  - Operating room. Annual systems survey shows strong gains in profit margins on
      operations, but the bottom line takes a hit.

PMID- 15977680
TI  - Straight talk--new approaches in healthcare. The road to a digital healthcare
      community. Panel discussion.
AB  - Healthcare organizations are often criticized for skeptically deferring the
      purchase of information technologies that can improve the safety, quality and
      efficiency of patient care. But some forward-thinking healthcare organizations
      have broken out of the pack, leveraging leading-edge technologies to gain a
      competitive advantage. They integrate information technologies across the
      enterprise, allowing them to compress processes, adapt to market forces and
      generate the kind of quality data that payers, physicians and patients expect. In
      this installment of Straight Talk, we discuss the strategies that three
      organizations have deployed successfully to move themselves along the digital
      continuum. Modern Healthcare and PricewaterhouseCoopers present Straight Talk.
      The session on digital healthcare was held on May 3, 2005 at Modern Healthcare's
      Chicago headquarters. Fawn Lopez, publisher of Modern Healthcare, was the
      moderator.

PMID- 15977681
TI  - By the numbers. Top 10 healthcare provider consultants ranked by 2004 total
      healthcare practice revenue.

PMID- 15977682
TI  - The impact of a multi-disciplinary management approach on diabetic control in
      young Saudi patients.
AB  - The increasing incidence of diabetes mellitus worldwide makes traditional
      approaches to its management inadequate. The involvement of young people in this
      diabetic "epidemic" provides an opportunity to apply a multidisciplinary approach
      to its management, to help reduce the huge burden of the disease and its
      complications. In 1998, we established a diabetic clinic for young adults,
      located within a privately owned company health center, because they were not
      receiving adequate attention in the adult clinic. Our purpose was to optimize
      diabetes control by teaching about diet, exercise, medications, and other
      practical diabetic management issues. In this special communication, we describe
      the organization of the clinic and present our experience with 105 patients in
      the first 4 years. Diabetic control as measured by serial glycosylated
      haemoglobin levels (HbA1c) and the occurrence and severity of diabetic
      ketoacidosis improved in our patients over those 4 years. Studies in the West
      have shown that small reductions in HbA1c have translated into dramatic decreases
      in microvascular complications. Application of this model to a larger population
      group is needed. Further study may help determine whether to adopt this pattern
      of care more widely, with its obvious benefits in reduction of diabetic
      morbidity, mortality and health care cost. We also identified three groups that
      may require special attention: females, young adults who develop the disease as
      children, and adolescents who have no regular adult supervision.

PMID- 15977683
TI  - Vaccination against invasive pneumococcal disease in Saudi Arabia: where do we
      stand?

PMID- 15977684
TI  - Streptococcus pneumoniae serotypes/serogroups causing invasive disease in Riyadh,
      Saudi Arabia: extent of coverage by pneumococcal vaccines.
AB  - BACKGROUND: Serogroup distribution of sterile site pneumococcal isolates varies
      between developing and developed countries as well as between different
      geographical regions. The potential efficacy of any pneumococcal vaccine depends
      on the degree of representation of the prevalent serogroups in the vaccine. We
      conducted this study to determine the prevalent pneumococcal serogroups causing
      invasive infections in Riyadh, Saudi Arabia and to estimate the coverage by the
      various pneumococcal conjugate vaccines. METHODS: S. pneumoniae isolated between
      February 2000 and November 2001 from sterile sites of patients of all age groups
      were collected from 8 major hospitals in Riyadh and serogrouped using the latex
      agglutination method. RESULTS: Isolates from 78 patients, 72% of whom were
      children, were studied. Eighty-eight percent of the isolates belonged to only 10
      serogroups/serotypes, namely 6 and 19, 1 and 15, 14 and 23, 7, 18 and 22, in
      descending order of frequency. Potential coverage of the 7-valent, 9-valent, and
      11-valent conjugate vaccines were 54%, 65% and 73%, respectively. The rate of
      reduced penicillin susceptibility in the serogroups represented in the 7-valent
      conjugate vaccine was significantly higher than in the non-vaccine serogroups
      (62% vs. 25%; P=0.0023). CONCLUSION: The currently available 7-valent
      pneumococcal conjugate vaccine provides sub-optimal coverage to serogroups
      causing invasive diseases in our community. However, this vaccine would be a
      useful adjunct to penicillin prophylaxis in at-risk patients in the community.
      The effectiveness of the vaccine would be greater if serotype 15 could be
      included.

PMID- 15977685
TI  - HIV/AIDS epidemic features and trends in Saudi Arabia.
AB  - BACKGROUND: More than 60 million persons have been infected since AIDS was
      described in 1981. By the end of 2003, an estimated 40 million individuals were
      living with HIV globally. The surveillance of HIV/AIDS still faces challenges in
      Saudi Arabia. This study describes the pattern and characteristics of HIV/AIDS
      cases in Saudi Arabia. METHODS: This descriptive analytic study describes the
      reported HIV/AIDS data for all notifiable cases during the period 1984 to 2003 in
      the Kingdom of Saudi Arabia. Case definitions based on ELISA and Western Blot
      tests were used. Age, sex and regional distribution were studied in addition to
      survival rates. RESULTS: As of 2003, 1743 Saudi nationals and 6064 non-Saudi HIV
      cases were reported. Among Saudis, 872 were AIDS cases. Males accounted for 1329
      HIV infections, comprising 77%, with a male-to-female ratio of about 3:1. Adults
      15-49 years constituted 78% of cases, including 46% of cases infected through
      sexual activity, while 33% of reported HIV seropositive cases had already died.
      Most cases (67%) were registered in Jeddah, Riyadh and Dammam. Infection through
      blood transfusion declined with no reported cases since 2001. CONCLUSION: The
      number of reported HIV infections in KSA has increased in the last few years.
      Using the coverage rate estimating method, the number of Saudi HIV infections
      since the emergence of the epidemic was estimated to be 2640 cases as of the
      beginning of the year 2004. The estimated number of HIV infections is almost one
      and one-half times the reported number, indicating that a problem of
      underreporting of HIV/AIDS cases still exists.

PMID- 15977687
TI  - Sentinel lymph nodes and breast carcinoma: analysis of 70 cases by frozen
      section.
AB  - BACKGROUND: The sentinal node biopsy (SNB) is a reliable method for determining
      the status of the regional lymph nodes in patients with breast cancer. SNB
      technology is evolving rapidly, but no standardization has yet been accomplished.
      The aim of this study is to discuss the accuracy of this procedure and the
      optimal method for identifying micrometastases. METHODS: We collected data from
      70 women with primary invasive breast carcinoma who underwent SNB for breast
      cancer. We examined two frozen sections levels from each half of each lymph node,
      as well as a cytology imprint before arriving at the frozen section diagnosis.
      Immunohistochemistry with pancytokeratin (AE1/AE3) was done on the paraffin
      sections. For the association between the lymph node size and the possibility of
      metastases, Student's t test was used and a P value of less than 0.05 was
      regarded as significant. RESULTS: The number of patients with metastases in SNB
      was 19, from which 15 cases were correctly diagnosed in frozen sections/imprints
      and four cases were false negative. The axillary toilet from all cases with SNB
      metastases smaller than 2 mm showed no additional positive nodes. Lymph node
      diameter showed a significant association with sentinel node status (P<0.0001).
      CONCLUSION: Frozen section examination of SNB from patients with breast carcinoma
      is both specific (100%) and sensitive (79%). Diagnosis of lobular carcinoma can
      be difficult, and may require immunohistochemistry with cytokeratin for
      diagnosis. Small metastases in a non-optimal frozen section may be difficult to
      discern. Cytology imprints add nothing to the diagnosis.

PMID- 15977686
TI  - Protocol-driven vs. physician-driven electrolyte replacement in adult critically
      ill patients.
AB  - BACKGROUND: The intensive care unit is a dynamic environment, where high numbers
      of patients cared for by health care workers of different experiences and
      backgrounds might result in great variability in patient care. Protocol-driven
      interventions may facilitate timely and uniform care of common problems, like
      electrolyte disturbances. We prospectively compared protocol-driven (PRD) vs.
      physician-driven (PHD) electrolyte replacement in adult critically ill patients.
      PATIENTS AND METHODS: In the first month of the two-month study, potassium,
      magnesium, and phosphate levels were checked by a physician before ordering
      replacement (PHD replacement period). Over the second month, ICU nurses proceeded
      with replacement according to the protocol (PRD replacement period). We collected
      demographic data, admission diagnosis, number of potassium, magnesium, and
      phosphate levels done per day, number of low levels per day, number of
      replacements per day, time between availability of results to ordering
      replacement, time to starting replacement, post-replacement levels, serum
      creatinine, replacement dose, arrhythmias and replacement route. RESULTS: During
      the PHD replacement period, 43 patients meeting the inclusion criteria were
      admitted to the ICU, while 44 were admitted during the PRD month. The mean time
      (minutes) from identifying results to replacement of potassium, phosphate and
      magnesium was significantly longer with PHD replacement compared with PRD
      replacement (161, 187, and 189 minutes vs. 19, 26, and 19 minutes) (P<0.0001).
      The number of replacements needed and not given was also significantly lower in
      the PRD replacement period compared with the PHD replacement period (2, 4, and 0
      compared with 9, 6 and 0) (P<0.05). No patients had high post-replacement serum
      concentrations of potassium, phosphate or magnesium. CONCLUSIONS: This study
      shows that a protocol-driven replacement strategy for potassium, magnesium and
      phosphate is more efficient and as safe as a physician-driven replacement
      strategy.

PMID- 15977688
TI  - Observations on the management of acute pain crisis in adult sickle cell disease
      in eastern Saudi Arabia.
AB  - BACKGROUND: Sickle cell pain crisis continues to challenge patients and health
      professionals in places like Saudi Arabia, where the disease is common, and use
      of narcotic analgesics is strictly controlled. We sought to find the most
      effective and appropriate pain control regime for adult sickle cell pain crisis
      in Saudi Arabian patients. PATIENTS AND METHODS: Adult sickle cell disease
      patients in crisis, treated initially in the emergency room of a private health
      center, usually undergo further treatment with different pain control regimes in
      an observation ward. We compared the adequacy of pain conrol during the three
      recent years (2000-2002) with those of the preceding three (1995-1997). RESULTS:
      Treatment with regular opiates supplemented with oral analgesics during the
      second three-year period produced better results than "on demand" regimes. The
      former regimen enabled about 83% of patients from the second three-year period to
      be discharged home within two days compared with 71% during the first three-year
      period (P<0.05). A minority of patients needed more time for pain resolution.
      Patient response to oral analgesics was variable and females appeared to fare
      better than males. DISCUSSION: Greater empathy and individualized treatment are
      required for sickle cell pain crisis patients because of their variable clinical
      presentation, response to medications, and the regularity of pain in their lives.
      The observed gender differences in pain response require further study.

PMID- 15977689
TI  - Minimal exhaled nitric oxide production in the lower respiratory tract of healthy
      children aged 2 to 7 years.
AB  - BACKGROUND: Exhaled nitric oxide (eNO) is elevated in inflammatory airway
      conditions, e.g. asthma. We measured eNO levels in normal preschool children for
      whom there is little data available and in whom the prevalence of asthma is high.
      SUBJECTS AND METHODS: Fifty children, 2-7 years old, undergoing elective surgery,
      excluding airway procedures, were recruited. Children with known respiratory
      disease or acute viral infections were excluded. Gas for eNO measurement was
      collected in a non-diffusion bag via 1) the mask after inhalation induction of
      anesthesia, 2) endotreacheal tube (ETT) or laryngeal mask airway (LMA), and 3)
      during emergence. Measurement was off-line by chemiluminescent analyzer. RESULTS:
      Mean eNO level by mask was 10.23 ppb (mean value+/-SD of 8.8-11.1 ppb) after
      induction and 8.35 ppb (mean value+/-SD of 5.9-10.8 ppb) on emergence. Mean eNO
      for the intubated group (n=25) was 0.75 ppb (mean value+/-SD of 0.4-1 ppb)
      (P<0.0001 vs mask); mean eNO for the LMA group (n=25) was 2.6 ppb (mean value+/
      SD of 2-3.2 ppb), which differed from the mask (P<0.0001), and from ETT values
      (P<0.0001). CONCLUSIONS: Most eNO is produced by the upper airway in healthy pre
      school children. The lower airway constitutive eNO production is very low. The
      LMA does not completely isolate the upper airway and current mask collection
      techniques allow significant contamination of samples by sino-nasal eNO
      production in young children.

PMID- 15977690
TI  - Fetal sex and leptin concentrations in pregnant females.
AB  - BACKGROUND: Adult females have significantly more leptin than males. We
      investigated the effect of fetal sex on levels of leptin and other pregnancy
      hormones (progesterone, estradiol, FSH, LH and beta hCG) in pregnant females
      during different stages of pregnancy. PATIENTS AND METHODS: Serum leptin levels
      in pregnant females followed at King Khaled University Hospital, Riyadh, Saudi
      Arabia in the year 2001 were estimated at the first, second, and third trimester
      of pregnancy as well as after delivery. Progesterone, estradiol, FSH, LH and beta
      hCG levels were also measured. RESULTS: Leptin levels were significantly higher
      during all three trimesters in the pregnant females carrying female fetuses
      compared with those with male fetuses, while other hormones did not differ
      between the two groups. After delivery, the leptin levels decreased in both
      groups, and were still higher in the females who delivered baby girls, but the
      results were not statistically significant. CONCLUSION: These finding suggests
      that leptin might play a role in sex regulation during embryonic development.

PMID- 15977691
TI  - A population-based screening for gestational diabetes mellitus in non-diabetic
      women in Bahrain.
AB  - BACKGROUND: Maternal hyperglycemia is considered a risk factor for fetal
      morbidity. Since there is a high prevalence of diabetes mellitus among the
      population of Bahrain, we conducted a prospective population-based study of
      gestational diabetes mellitus (GDM) in non-diabetic pregnant women. SUBJECTS AND
      METHODS: All non-diabetic pregnant women attending antenatal clinics during
      January 2001 to December 2002 (n=10,495) were screened for GDM during the 24th to
      28th weeks of gestation. All positive subjects based on a 50-g glucose challenge
      test (GCT) were further evaluated by a diagnostic 75-g oral glucose tolerance
      test (OGTT). The birth weight of the child and post-delivery insulin resistance
      were monitored. The homeostasis model of insulin resistance (HOMA-IR) was used to
      assess insulin resistance. RESULTS: Of 10,495 non-diabetic pregnant women
      screened, 32.8% (n=3443) had plasma glucose > or = 7.8 mmol/L (140 mg/dL) in the
      GCT. The 75-g OGTT found a prevalence of GDM of 13.5%. There were twice as many
      Bahrainis as expatriates. Of children born to women with GDM, 6.5% had a birth
      weight > 4000 g. Post-delivery evaluation of insulin resistance indicated that
      33% of women with GDM had a HOMA-IR value > 2. CONCLUSION: The population of
      Bahrain is a high-risk ethnic group for GDM. The association of insulin
      resistance in the post-gravid state with GDM among 33% of the study population
      suggests that insulin resistance, the possible cause of the pathophysiological
      mechanism underlying the development of gestational diabetes, continues in the
      post gravid state.

PMID- 15977692
TI  - Predictors of type and site of first acute myocardial infarction in men and
      women.
AB  - BACKGROUND: The importance of pathophysiological mechanisms involved in onset of
      acute myocardial infarction (AMI) differs with age, gender, and risk profiles.
      Diversity in the triggering of cardiovascular events has been observed,
      particularly between men and women. Therefore, we investigated the relationship
      between age, gender, and risk factors and location of AMI and the presence of Q
      waves in ECG. PATIENTS AND METHODS: Data was obtained from a chart review of 2958
      patients with first AMI: 770 (26%) patients with non-Q-wave AMI and 2188 (74%)
      patients with Q-wave AMI. Four clinical groups were formed by predetermined
      criteria (anterior Q-wave, anterior non-Q-wave, inferior Q-wave, inferior non-Q
      wave). A logistic regression was performed to assess independent predictors of
      AMI type and site. RESULTS: Key findings were: 1) inferior non-Q-wave AMI was
      more frequent in young women (P<0.001); 2) inferior Q-wave AMI was more common in
      young men (P<0.001); 3) anterior non-Q-wave AMI was more common in older men
      (P<0.001). Multivariate analysis revealed that independent predictors of anterior
      non-Q-wave AMI were age over 65 (P=0.002), male gender (P=0.04) and
      hypercholesterolemia (P=0.0003), and that predictors of inferior Q-wave AMI were
      male gender (P<0.0001), smoking (P=0.04) and diabetes (P=0.049). In the gender
      subgroup analyses, age <45 years (P=0.04), hypecholesterolemia (P=0.02) and
      smoking (P=0.01) were independent predictors of inferior Q-wave AMI whereas age
      >65 years (P<0.0001) and smoking (P=0.0003) were predictors of anterior non-Q
      wave AMI in men. In women, age <45 years (P<0.0001) and smoking (P=0.02) were
      independent predictors of non-Q-wave AMI and hypercholesterolemia (P=0.02) was a
      predictor of inferior Q-wave AMI. CONCLUSION: The link between particular types
      and the site of AMI and age, gender and risk factors suggest that the importance
      of pathophysiological mechanisms for onset of AMI differs according to sex and
      age subgroup.

PMID- 15977693
TI  - Botulinum toxin injection versus internal anal sphincterotomy for the treatment
      of chronic anal fissure.
AB  - BACKGROUND: Anal fissure is a chronic condition characterized by painful
      defecation and rectal bleeding. The aim of this study was to compare injection of
      botulinum toxin versus surgical sphincterotomy for treatment of chronic anal
      fissure. PATIENTS AND METHODS: In a quasi-experimental trial in a university
      hospital in Kerman, 50 patients diagnosed with chronic anal fissure received 20
      units botulinum toxin (n=25) or underwent lateral internal sphincterotomy (n=25).
      All patients were evaluated for pain, bleeding and healing of the fissure from
      one to six months later by another surgeon. The data was analyzed by SPSS
      software with the Mann-Whitney and Fisher's exact tests. RESULTS: One month after
      treatment, the rate of healing and bleeding in the operation group was better
      than in the toxin group (P<0.05), while pain was equal. After two months, none of
      the patients in either group had complications. After six months follow-up,
      bleeding, pain and healing were better in the operation group. CONCLUSION: In the
      clinical evaluation, botulinum toxin is an effective alternative nonsurgical
      modality for the treatment of chronic anal fissure. We recommend botulinum toxin
      as the first step in treatment because of the 60% chance of cure with an easily
      performed treatment.

PMID- 15977694
TI  - Anthrax vaccines.
AB  - Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus
      anthracis. The risk of inhalation infection is the main indication for anthrax
      vaccination. Pre-exposure vaccination is provided by an acellular vaccine
      (anthrax vaccine adsorbed or AVA), which contains anthrax toxin elements and
      results in protective immunity after 3 to 6 doses. Anthrax vaccine precipitated
      (AVP) is administered at primovaccination in 3 doses with a booster dose after 6
      months. To evoke and maintain protective immunity, it is necessary to administer
      a booster dose once at 12 months. In Russia, live spore vaccine (STI) has been
      used in a two-dose schedule. Current anthrax vaccines show considerable local and
      general reactogenicity (erythema, induration, soreness, fever). Serious adverse
      reactions occur in about 1% of vaccinations. New second-generation vaccines in
      current research programs include recombinant live vaccines and recombinant sub
      unit vaccines.

PMID- 15977695
TI  - Molecular fingerprinting reveals familial transmission of rifampin-resistant
      tuberculosis in Kuwait.

PMID- 15977696
TI  - Nutritional koilonychia in 32 Iraqi subjects.

PMID- 15977697
TI  - Angina and sudden cardiac death caused by anomalous right coronary artery origin
      from above the left coronary cusp.

PMID- 15977698
TI  - Primary neuroendocrine carcinoma (Merkel's cell carcinoma) of the vulva mimicking
      as a Bartholin's gland abscess.

PMID- 15977699
TI  - Congenital pyloric atresia: a report of two cases.

PMID- 15977700
TI  - Wandering spleen associated with a splenic cyst.

PMID- 15977701
TI  - A newborn female with a smooth mass in the region of the base of the tongue.

PMID- 15977702
TI  - Missed intra-abdominal malignancies after laparoscopic cholecystectomy.

PMID- 15977703
TI  - DiGeorge's syndrome presenting as hypocalcemia in an adult.

PMID- 15977704
TI  - Re: Assay of flouride levels in drinking water.

PMID- 15977705
TI  - WHO appeals for 60 million US dollars to prevent disease outbreaks in tsunami
      affected Southeast Asia.

PMID- 15977706
TI  - [Partnering for better care].

PMID- 15977707
TI  - [Treatment of acute stroke].
AB  - The aim of this review is to discuss the different treatment strategies of acute
      stroke. The main studies performed with intravenous or intra-arterial
      thrombolysis are reported as well as the recent results concerning the use of
      IIb/IIIa platelet receptors antagonists. We will also discuss the potential
      effect of ultrasound on systemic thrombolysis. Finally are mentioned the most
      important measures to avoid medical and neurological complications which may
      occur during the acute phase of stroke.

PMID- 15977708
TI  - [Is there a treatment for Alzheimer's disease?].
AB  - Alzheimer's disease is a frequent neurodegenerative disease, which affects more
      than one third of elderly persons over 80 years. No curative treatment is
      currently available for this disease, but symptomatic treatments have produced
      significant improvements in patients' condition. Cholinesterase inhibitors should
      be prescribed for early and moderate stages and memantine for more severe stages
      of the disease. These drugs have an impact on cognitive performances, may delay
      functional decline and improve behaviour disturbances. From a preventive
      perspective, evidence of benefit from early management of vascular risk factors
      is accumulating. In the near future, the improved comprehension of the underlying
      mechanisms of Alzheimer's disease will hopefully bring new treatments, thats will
      delay or modify its course.

PMID- 15977709
TI  - [Acute migraine treatment].
AB  - Migraine is a chronic neurological disorder of recurring and painful episodic
      headache. Migraine is often associated with functional impairment and leads to
      important costs in lost productivity. Migraine is underrecognized and
      undertreated. Diagnosis is based on the reporting headache characteristics and
      associated symptoms. The physical and neurological examinations are normal.
      Several drugs are used for acute migraine treatment. Non-narcotic analgesics and
      NSAIDs can be useful, but a new class of selective 5 HT 1B/1D agonists, known as
      the triptans, is now commonly prescribed. The efficacy of the treatment can be
      increased by early administration in an attack.

PMID- 15977710
TI  - [Current treatment of Parkinson's disease: problems and controversies].
AB  - Treating patients with Parkinson's disease is not an easy task for the physician
      who is facing a disease well responsive to symptomatic therapy, yet escaping any
      curative approaches. In spite of the large therapeutic armamentarium available,
      many issues remained unsolved, as indications of a particular therapeutic agent
      are only loosely defined and evolving according to various parameters such as
      disease progression and severity, the profile of potentially serious adverse
      effects, the physician's level of expertise and patient's expectations. The
      growing experience acquired with subthalamic nucleus deep brain stimulation has
      shown that indications for such a surgery have to be cautiously examined. After
      initial therapeutic enthusiasm, we are now at a time of problems and
      controversies.

PMID- 15977711
TI  - [Current epilepsy treatment in adults].
AB  - The prevalence of epilepsy is about 1%. Only two thirds of these patients respond
      satisfactorily to an antiepileptic drug (AED) treatment. New AED did not clearly
      improve this overall efficacy, but often show a better tolerability as compared
      to old AED. This may allow a more targeted choice, especially in some delicate
      clinical situations, such as for the treatment of women in childbearing age, or
      patients receiving other drugs with possible pharmacokinetic interactions.
      Invasive approaches should be considered early in the course of treatment
      resistant epilepsy, and may offer a complete seizure remission in selected cases.
      On the background of recent acquisitions from the literature, the pros and cons
      of different treatment options are presented. This is followed by the discussion
      of some clinical relevant situations.

PMID- 15977712
TI  - [Immunomodulatory/suppressive treatments in neurology].
AB  - Immunomodulatory/suppressive treatments are frequently used in neurological
      disorders affecting the central and peripheral nervous system. Demyelinating
      disorders are a good example of a wide application of the various types of
      existing therapies. Although these therapies are still mostly not disease
      specific, their combination with more targeted molecules appears most relevant
      for diseases with multiple pathogenic mechanisms.

PMID- 15977713
TI  - [Highlights from the American College of Cardiology Annual Scientific Session
      2005: March 5-9, 2005, Orlando, Florida].

PMID- 15977715
TI  - [Directed death and assisted suicide].

PMID- 15977714
TI  - [A recount of an ethic commission meeting ].

PMID- 15977716
TI  - [Improved treatment of Crohn's disease].

PMID- 15977717
TI  - [When The Lancet lectures morality to American physicians].

PMID- 15977719
TI  - [Concern for preventive medicine].

PMID- 15977718
TI  - [Antidepressants and suicidal risk].

PMID- 15977720
TI  - Trends in indirect dentistry: 3. Luting materials.
AB  - Luting materials play a central role in indirect dentistry. Active materials
      which bond to tooth and restoration may aid retention of restorations, while
      passive materials merely fill the gap between crown and tooth. The properties of
      currently available luting materials are discussed, with resin-modified glass
      ionomer and resin materials being found to exhibit optimum properties. However,
      resin luting materials have been technique sensitive to use, but the advent of
      self-adhesive resin luting materials has overcome most of the technique problems
      during placement of restorations. Resin materials are indicated for luting all
      ceramic restorations. CLINICAL RELEVANCE: Correct choice of a luting material
      with optimum physical properties is central to success in indirect dentistry.

PMID- 15977721
TI  - The role of the dental team in preventing and diagnosing cancer: 2. Oral cancer
      risk factors.
AB  - Oral cancer is among the ten most common cancers world-wide, and is especially
      seen in disadvantaged older males. Cancer arises as a consequence of DNA
      mutations causing multiple molecular genetic events in many chromosomes and
      genes, leading to cell dysregulation. Tobacco and alcohol use are extremely
      important in oral mutagenesis. Environmental factors such as infective agents and
      genetic factors are implicated in a minority of patients. CLINICAL RELEVANCE:
      Dental staff can advise on lifestyle changes for the prevention of potentially
      malignant oral disease and thereby protect their patients, staff, colleagues,
      families and acquaintances, having the opportunity to make an impact on improving
      the survival rate and morbidity of oral cancer by detecting both potentially
      malignant and malignant oral lesions.

PMID- 15977722
TI  - Obturators for acquired palatal defects.
AB  - The developing role of the prosthodontist in the head and neck cancer team is
      discussed and a sequence of care given for patients who will require the
      restoration by prosthetic means of surgically created palatal defects. Various
      styles of definitive obturators are described. CLINICAL RELEVANCE: A knowledge of
      the care of patients with palatal defects is of value to GDPs and to members of
      the head and neck cancer team.

PMID- 15977723
TI  - An overview of the use of lasers in general dental practice: 2. Laser
      wavelengths, soft and hard tissue clinical applications.
AB  - The profession now benefits from many different laser wavelengths that enable
      their use in nearly every dental specialty. This article will cover these
      wavelengths and their uses for soft and hard tissue procedures. CLINICAL
      RELEVANCE: There are many laser wavelengths available but their use within
      dentistry is quite tissue specific. It is hoped the reader will be able to decide
      which wavelength is best for a particular procedure.

PMID- 15977724
TI  - How to write a case report.
AB  - Case reports form an invaluable source of learning and discussion material. The
      aim of this article is to provide some guidance to help authors who are thinking
      of submitting reports for future publication. Some common pitfalls are
      highlighted, as well as useful hints to increase the authors' chances of
      publication. CLINICAL RELEVANCE: Case reports often introduce readers to new
      clinical techniques and allow them so see how treatment can be made more
      efficient and effective.

PMID- 15977725
TI  - Physical signs for the general dental practitioner.

PMID- 15977726
TI  - Needle steering and motion planning in soft tissues.
AB  - In this work, needle insertion into deformable tissue is formulated as a
      trajectory planning and control problem. A new concept of needle steering has
      been developed and a needle manipulation Jacobian defined using numerical needle
      insertion models that include needle deflection and soft tissue deformation. This
      concept is used in conjunction with a potential-field-based path planning
      technique to demonstrate needle tip placement and obstacle avoidance. Results
      from open loop insertion experiments are provided.

PMID- 15977727
TI  - Fat and hydration monitoring by abdominal bioimpedance analysis: data
      interpretation by hierarchical electrical modeling.
AB  - In a previous publication, it was demonstrated that the abdominal subcutaneous
      fat layer thickness (SFL) is strongly correlated with the abdominal electrical
      impedance when measured with a transversal tetrapolar electrode arrangement. This
      article addresses the following questions: 1) To which extent do different
      abdominal compartments contribute to the impedance? 2) How does the hydration
      state of tissues affect the data? 3) Can hydration and fat content be assessed
      independently? For simulating the measured data a hierarchical electrical model
      was built. The abdomen was subdivided into three compartments (subcutaneous fat,
      muscle, mesentery). The true anatomical structure of the compartment boundaries
      was modeled using finite-element modeling (FEM). Each compartment is described by
      an electrical tissue model parameterized in physiological terms. Assuming the
      same percent change of the fat fraction in the mesentery and the SFL the model
      predicts a change of 1,24 omega/mm change of the SFL compared to 1,1 omega/mm
      measured. 42% of the change stem from the SFL, 56% from the mesentery and 2% from
      changes of fat within the muscle compartment. A 1% increase of the extracellular
      water in the muscle is not discernible from a 1% decrease of the SFL. The
      measured data reflect not only the SFL but also the visceral fat. The tetrapolar
      electrode arrangement allows the measurement of the abdominal fat content only if
      the hydration remains constant.

PMID- 15977728
TI  - Noninvasive measurement and analysis of intestinal myoelectrical activity using
      surface electrodes.
AB  - Intestinal myoelectrical activity (IMA), which determines bowel mechanical
      activity, is the result of two components: a low-frequency component [slow wave
      (SW)] that is always present, and a high-frequency component [spike bursts (SB)]
      which is associated with bowel contractions. Despite of the diagnostic
      significance of internal recordings of IMA, clinical application of this
      technique is limited due to its invasiveness. Thus, surface recording of IMA
      which is also called electroenterogram (EEnG) could be a solution for noninvasive
      monitoring of intestinal motility. The aim of our work was to identify slow wave
      and spike burst activity on surface EEnG in order to quantify bowel motor
      activity. For this purpose, we conducted simultaneous recordings of IMA in bowel
      serosa and on abdominal surface of five Beagle dogs in fast state. Surface EEnG
      was studied in spectral domain and frequency bands for slow wave and spike burst
      energy were determined. Maximum signal-to-interference ratio (7.5 dB +/- 36%) on
      SB frequency band was obtained when reducing upper frequency limit of signal
      analysis. Energy of external EEnG in reduced SB frequency band (2-7.9 Hz)
      presented a high correlation (0.71 +/- 7%) with internal intensity of
      contractions. Our results suggest that energy of SB can be quantified on external
      EEnG which could provide a noninvasive method for monitoring intestinal
      mechanical activity.

PMID- 15977729
TI  - Soft tissue artifact compensation in knee kinematics by double anatomical
      landmark calibration: performance of a novel method during selected motor tasks.
AB  - The purpose of the present work was to describe and assess the performance on two
      selected subjects of a new method for the compensation of soft tissue artifact on
      knee rotations and translations during the execution of step up/down, sit-to
      stand/stand-to-sit, and flexion against gravity. Soft tissue artifact has been
      recognized as the most critical source of error in gait analysis data. Its
      propagation strongly affects joint angles, in particular those characterized by a
      small range of motion, such as knee ab/adduction and internal/external rotation.
      This may be critical in the exploitation of gait analysis data for clinical
      decisions. The proposed method is based on the flexion/extension angle
      interpolation of two anatomical landmark calibrations taken at the extremes of
      motion. Its performance on knee rotation and translations was tested on a
      kinematics data-set obtained by the synchronous combination of traditional
      stereophotogrammetry and 3-D fluoroscopy. The newly proposed method was extremely
      effective on the compensation of soft tissue artifact propagation to knee
      rotations, in particular mean values of the root mean square error on
      ab/adduction and internal/external rotation angles decreased from 3.7 degrees and
      3.7 degrees to 1.4 degrees and 1.6 degrees, respectively, with respect to single
      calibration. Mainly, knee translations calculated from stereophotogrammetric data
      using the proposed compensation method were found to be reliable with respect to
      the fluoroscopy-based gold standard. The residual mean values of the root mean
      square error were 2.0, 2.8, and 2.1 mm for anterior/posterior, vertical, and
      medio/lateral translations, respectively.

PMID- 15977730
TI  - A 2-D ECG compression method based on wavelet transform and modified SPIHT.
AB  - A two-dimensional (2-D) wavelet-based electrocardiogram (ECG) data compression
      method is presented which employs a modified set partitioning in hierarchical
      trees (SPIHT) algorithm. This modified SPIHT algorithm utilizes further the
      redundancy among medium- and high-frequency subbands of the wavelet coefficients
      and the proposed 2-D approach utilizes the fact that ECG signals generally show
      redundancy between adjacent beats and between adjacent samples. An ECG signal is
      cut and aligned to form a 2-D data array, and then 2-D wavelet transform and the
      modified SPIHT can be applied. Records selected from the MIT-BIH arrhythmia
      database are tested. The experimental results show that the proposed method
      achieves high compression ratio with relatively low distortion and is effective
      for various kinds of ECG morphologies.

PMID- 15977731
TI  - Bayesian solutions and performance analysis in bioelectric inverse problems.
AB  - In bioelectric inverse problems, one seeks to recover bioelectric sources from
      remote measurements using a mathematical model that relates the sources to the
      measurements. Due to attenuation and spatial smoothing in the medium between the
      sources and the measurements, bioelectric inverse problems are generally ill
      posed. Bayesian methodology has received increasing attention recently to combat
      this ill-posedness, since it offers a general formulation of regularization
      constraints and additionally provides statistical performance analysis tools.
      These tools include the estimation error covariance and the marginal probability
      density of the measurements (known as the "evidence") that allow one to
      predictively quantify and compare experimental designs. These performance
      analysis tools have been previously applied in inverse electroencephalography and
      magnetoencephalography, but only in relatively simple scenarios. The main
      motivation here was to extend the utility of Bayesian estimation techniques and
      performance analysis tools in bioelectric inverse problems, with a particular
      focus on electrocardiography. In a simulation study we first investigated whether
      Bayesian error covariance, computed without knowledge of the true sources and
      based on instead statistical assumptions, accurately predicted the actual
      reconstruction error. Our study showed that error variance was a reasonably
      reliable qualitative and quantitative predictor of estimation performance even
      when there was error in the prior model. We also examined whether the evidence
      statistic accurately predicted relative estimation performance when distinct
      priors were used. In a simple scenario our results support the hypothesis that
      the prior model that maximizes the evidence is a good choice for inverse
      reconstructions.

PMID- 15977732
TI  - Fast wavelet estimation of weak biosignals.
AB  - Wavelet-based signal processing has become commonplace in the signal processing
      community over the past decade and wavelet-based software tools and integrated
      circuits are now commercially available. One of the most important applications
      of wavelets is in removal of noise from signals, called denoising, accomplished
      by thresholding wavelet coefficients in order to separate signal from noise.
      Substantial work in this area was summarized by Donoho and colleagues at Stanford
      University, who developed a variety of algorithms for conventional denoising.
      However, conventional denoising fails for signals with low signal-to-noise ratio
      (SNR). Electrical signals acquired from the human body, called biosignals,
      commonly have below 0 dB SNR. Synchronous linear averaging of a large number of
      acquired data frames is universally used to increase the SNR of weak biosignals.
      A novel wavelet-based estimator is presented for fast estimation of such signals.
      The new estimation algorithm provides a faster rate of convergence to the
      underlying signal than linear averaging. The algorithm is implemented for
      processing of auditory brainstem response (ABR) and of auditory middle latency
      response (AMLR) signals. Experimental results with both simulated data and human
      subjects demonstrate that the novel wavelet estimator achieves superior
      performance to that of linear averaging.

PMID- 15977733
TI  - Identification of transient renal autoregulatory mechanisms using time-frequency
      spectral techniques.
AB  - Identification of the two principal mediators of renal autoregulation from time
      series data is difficult, as both the tubuloglomerular feedback (TGF) and
      myogenic (MYO) mechanisms interact and share a common effector, the afferent
      arteriole. Moreover, although both mechanisms can exhibit oscillations in well
      characterized frequency bands, these systems often operate in nonoscillatory
      states not detectable by frequency-domain analysis. To overcome these
      difficulties, we have developed a new approach to the characterization of the TGF
      and MYO systems. A laser Doppler probe is used to measure fluctuations in local
      cortical blood flow (CBF) in response to spontaneous changes in blood pressure
      (BP) and to large imposed perturbations in BP, which elicit strong, simultaneous,
      transient, oscillatory blood flow responses. These transient responses are
      identified by high-resolution time-frequency spectral analysis of the time-series
      data. In this report, we compare four different time-frequency spectral
      techniques (the short-time Fourier transform (STFT), smoothed pseudo Wigner
      Ville, and two recently developed methods: the Hilbert-Huang transform and time
      varying optimal parameter search (TVOPS)) to determine which of these four
      methods is best suited for the identification of transient oscillations in renal
      autoregulatory mechanisms. We found that TVOPS consistently provided the best
      performance in both simulation examples and identification of the two
      autoregulatory mechanisms in actual data. While the STFT suffers in time and
      frequency resolution as compared to the other three methods, it was able to
      identify the two autoregulatory mechanisms. Taken together, our experience
      suggests a two level approach to the analysis of renal blood flow (RBF) data:
      STFT to obtain a low-resolution time-frequency spectrogram, followed by the use
      of a higher resolution technique, such as the TVOPS, if even higher time
      frequency resolution of the transient responses is required.

PMID- 15977734
TI  - Predicting dynamic range and intensity discrimination for electrical pulse-train
      stimuli using a stochastic auditory nerve model: the effects of stimulus noise.
AB  - This work investigates dynamic range and intensity discrimination for electrical
      pulse-train stimuli that are modulated by noise using a stochastic auditory nerve
      model. Based on a hypothesized monotonic relationship between loudness and the
      number of spikes elicited by a stimulus, theoretical prediction of the
      uncomfortable level has previously been determined by comparing spike counts to a
      fixed threshold, Nucl. However, no specific rule for determining Nucl has been
      suggested. Our work determines the uncomfortable level based on the excitation
      pattern of the neural response in a normal ear. The number of fibers
      corresponding to the portion of the basilar membrane driven by a stimulus at an
      uncomfortable level in a normal ear is related to Nucl at an uncomfortable level
      of the electrical stimulus. Intensity discrimination limens are predicted using
      signal detection theory via the probability mass function of the neural response
      and via experimental simulations. The results show that the uncomfortable level
      for pulse-train stimuli increases slightly as noise level increases. Combining
      this with our previous threshold predictions, we hypothesize that the dynamic
      range for noise-modulated pulse-train stimuli should increase with additive
      noise. However, since our predictions indicate that intensity discrimination
      under noise degrades, overall intensity coding performance may not improve
      significantly.

PMID- 15977735
TI  - Wavelet-based enhancement of lung and bowel sounds using fractal dimension
      thresholding--Part II: application results.
AB  - The application of the wavelet transform-fractal dimension-based (WT-FD) filter
      of Part I of this paper to real bioacoustic data, which include explosive lung
      sounds (ELS) and explosive bowel sounds (EBS) recorded from patients with
      pulmonary or gastrointestinal dysfunction, respectively, is presented in this
      paper. The objective of the latter is the evaluation of the performance of the WT
      FD filter on different types of bioacoustic signals, varying not only in their
      structural morphology but also in the degree of their noise contamination. As it
      is thoroughly described in Part I of this paper, the WT-FD filter uses the
      fractal dimension to form an efficient way of thresholding the WT coefficients at
      different resolution scales, keeping, thus, only those that can contribute to the
      accurate reconstruction of the ELS and EBS signals. Quantitative and qualitative
      analysis of the experimental results show an efficient performance of the WT-FD
      filter to circumvent the noise presence (100% detectability rate, 100%
      sensitivity, 100% specificity) by faithfully extracting the authentic structure
      of ELS and EBS from the background noise. The WT-FD filter does not require any
      noise reference signal or noise reference templates. The results from a noise
      stress test (mean cross-correlation index of the original and the estimated
      signal converging to 100%; mean normalized maximum amplitude error converging to
      0.7%) prove its robustness to various noise levels (0-20 dB), enabling its
      potential use in similar noise cases met in everyday clinical medicine.
      Furthermore, the efficient performance of the WT-FD filter facilitates the
      physician to better interpret the auscultation findings. Due to its simplicity
      and low computational cost, the WT-FD filter can possibly be implemented in a
      real-time context to serve as a tool for the continuous ELS and EBS screening.

PMID- 15977736
TI  - Quantifying motion in video recordings of neonatal seizures by robust motion
      trackers based on block motion models.
AB  - This paper introduces a methodology for the development of robust motion trackers
      for video based on block motion models. According to this methodology, the motion
      of a site between two successive frames is estimated by minimizing an error
      function defined in terms of the intensities at these frames. The proposed
      methodology is used to develop robust motion trackers that rely on fractional
      block motion models. The motion trackers developed in this paper are utilized to
      extract motor activity signals from video recordings of neonatal seizures. The
      experimental results reveal that the proposed motion trackers are more accurate
      and reliable than existing motion tracking methods relying on pure translation
      and affine block motion models.

PMID- 15977737
TI  - Using EMG to anticipate head motion for virtual-environment applications.
AB  - In virtual environment (VE) applications, where virtual objects are presented in
      a see-through head-mounted display, virtual images must be continuously
      stabilized in space in response to user's head motion. Time delays in head-motion
      compensation cause virtual objects to "swim" around instead of being stable in
      space which results in misalignment errors when overlaying virtual and real
      objects. Visual update delays are a critical technical obstacle for implementing
      head-mounted displays in applications such as battlefield simulation/training,
      telerobotics, and telemedicine. Head motion is currently measurable by a head
      mounted 6-degrees-of-freedom inertial measurement unit. However, even given this
      information, overall VE-system latencies cannot be reduced under about 25 ms. We
      present a novel approach to eliminating latencies, which is premised on the fact
      that myoelectric signals from a muscle precede its exertion of force, thereby
      limb or head acceleration. We thus suggest utilizing neck-muscles' myoelectric
      signals to anticipate head motion. We trained a neural network to map such
      signals onto equivalent time-advanced inertial outputs. The resulting network can
      achieve time advances of up to 70 ms.

PMID- 15977738
TI  - A safe transmission line for MRI.
AB  - Magnetic resonance imaging (MRI) has been established as a reliable and safe
      imaging method for the human body. However, electric conductors, such as cables
      situated near or in the human body, should be avoided because induced currents in
      the cables can cause hazardous heating in the surrounding tissue. In this paper,
      a new principle for the design of a transmission line is introduced and
      demonstrated, which is capable of avoiding dangerous heating of cables. The
      principle is based on transformers placed along the line, splitting the long line
      into several short not resonant and thus safe sections. A transformer design is
      introduced along with the theoretical aspects for both the avoidance of the
      undesired induced currents and the reduction of signal attenuation. Furthermore,
      the design fulfills the geometrical requirements of the side lumen of a standard
      catheter. Matching networks, whose elements are determined by power matching, are
      used to reduce signal attenuation by the transformers. A prototype was built to
      validate both theory and the simulations. As demonstrated in this work, it is
      possible to build safe transmission lines for MRI, making applications such as
      active catheter tracking possible. We expect that even new applications, such as
      safe intravascular imaging will be possible in a safe manner in the future.

PMID- 15977739
TI  - Electric fields in bone marrow substructures at power-line frequencies.
AB  - Bone marrow is known to be responsible for leukemia. In order to study the
      hypothesis relating power-line frequencies electromagnetic fields and childhood
      leukemia from a subcellular perspective, two models of bone marrow substructures
      exposed to electric field are computed numerically. A set of cancellous bone data
      obtained from computed tomography scan is computed using both the finite element
      method (FEM) and scalar potential finite difference method. A maximum electric
      field enhancement of 50% is observed. Another model of bone marrow stroma cells
      is implemented only in FEM using thin film approximation. The transmembrane
      potential (TMP) change across the gap junctions is found to range from several to
      over 200 microV. The two results suggest that imperceptible contact currents can
      produce biologically significant TMP change at least in a limited number of bone
      marrow stroma cells.

PMID- 15977740
TI  - On the development of a biomechatronic system to record tendon sliding movements.
AB  - The main goal of this paper is to study the feasibility of a novel implantable
      micro-system able to record information about tendon sliding movements by using
      contactless measurement devices (magnetic sources and sensors). The system, named
      "Biomechatronic Position Transducer" (BPT), can be used for the implementation of
      advanced control strategies in neuroprostheses. After a preliminary analysis
      based on finite element model simulations, an experimental setup was developed in
      order to simulate the recording conditions (the sensors fixed to the bones and
      the magnetic sources placed on the tendons). In order to limit the number of
      implanted components of the system, a fuzzy Mamdani-like architecture was
      developed to extract the information from the raw data. The results confirm the
      possibility of using the presented approach for developing an implantable micro
      sensor able to extract kinematic information useful for the control of
      neuroprostheses. Future works will go in the direction of integrating and testing
      the sensors and the electronic circuitry (to provide power supply and to record
      the data) during in vitro and in situ experiments.

PMID- 15977741
TI  - Effects of external pressure on arteries distal to the cuff during
      sphygmomanometry.
AB  - The aim of this study was to examine the effect on distal arteries of external
      pressure, applied by upper arm sphygmomanometer cuff. Photoplethysmographic (PPG)
      signals were measured on the index fingers of 44 healthy male subjects, during
      the slow decrease of cuff air pressure. For each pulse the ratio of PPG amplitude
      to its baseline (AM/BL) and its time delay (deltaTD) relative to the
      contralateral hand were determined as a function of cuff pressure. At cuff
      pressures equal to systolic blood pressure, pulses reappeared with the pulse time
      delay in the cuffed arm significantly greater than in the noncuffed arm, with
      (deltaTD) (mean +/- SD) 150 +/- 31 ms (p < 0.001). At cuff pressures equal to
      diastolic blood pressure (81 +/- 12 mmHg), deltaTD was 42 +/- 19 ms (p < 0.001),
      and at 50 mmHg, which is below diastolic blood pressure, (deltaTD) was still
      significantly positive at 6 +/- 9 ms (p < 0.001). AM/BL relative to its initial
      value rose at cuff pressures between systolic and diastolic blood pressure, then
      deceased to 0.6 +/- 0.41 (p < 0.001) at diastolic blood pressure and 0.54 +/-
      0.24 (p < 0.001) at 50 mmHg. The changes in (deltaTD) and AM/BL can be
      interpreted as originating from changes in the compliance of conduit arteries and
      small arteries with cuff inflation and deflation.

PMID- 15977742
TI  - Adaptive model initialization and deformation for automatic segmentation of T1
      weighted brain MRI data.
AB  - A fully automatic, two-step, T1-weighted brain magnetic resonance imaging (MRI)
      segmentation method is presented. A preliminary mask of parenchyma is first
      estimated through adaptive image intensity analysis and mathematical
      morphological operations. It serves as the initial model and probability
      reference for a level-set algorithm in the second step, which finalizes the
      segmentation based on both image intensity and geometric information. The Dice
      coefficient and Euclidean distance between boundaries of automatic results and
      the corresponding references are reported for both phantom and clinical MR data.
      For the 28 patient scans acquired at our institution, the average Dice
      coefficient was 98.2% and the mean Euclidean surface distance measure was 0.074
      mm. The entire segmentation for either a simulated or a clinical image volume
      finishes within 2 min on a modern PC system. The accuracy and speed of this
      technique allow us to automatically create patient-specific finite element models
      within the operating room on a timely basis for application in image-guided
      updating of preoperative scans.

PMID- 15977743
TI  - Fuzzy wavelet packet based feature extraction method and its application to
      biomedical signal classification.
AB  - In this paper, we develop an efficient fuzzy wavelet packet (WP) based feature
      extraction method for the classification of high-dimensional biomedical data such
      as magnetic resonance spectra. The key design phases involve: 1) a WP
      transformation mapping the original signals to many WP feature spaces and finding
      optimal WP decomposition for signal classification; 2) feature extraction based
      on the optimal WP decomposition; and 3) signal classification realized by a
      linear classifier. In contrast to the standard method of feature extraction used
      in WPs, guided by the criteria of signal compression or signal energy, our method
      is used to extract discriminatory features from the WP coefficients of the
      optimal decomposition. The extraction algorithm constructs fuzzy sets of features
      (via fuzzy clustering) to assess their discriminatory effectiveness. This paper
      includes a number of numerical experiments using magnetic resonance spectra.
      Classification results are compared with those obtained from common feature
      extraction methods in the WP domain.

PMID- 15977744
TI  - Fetal magnetocardiographic signals extracted by 'signal subspace' blind source
      separation.
AB  - In this paper, we apply independent component analysis to fetal
      magnetocardiographic data. In particular, we propose an extension of the
      "cumulant-based iterative inversion" algorithm to include a two-step "signal
      subspace" subdivision, which allows the user to control the number of components
      to be estimated by analyzing the eigenvalues distribution in an interactive way.
      Our results show that this method is a powerful means not only for the extraction
      of the cardiac signals from the background noise but also for a sharp separation
      of the baby's heart from the mother's.

PMID- 15977745
TI  - Wavelet-based enhancement of lung and bowel sounds using fractal dimension
      thresholding--Part I: methodology.
AB  - An efficient method for the enhancement of lung sounds (LS) and bowel sounds
      (BS), based on wavelet transform (WT), and fractal dimension (FD) analysis is
      presented in this paper. The proposed method combines multiresolution analysis
      with FD-based thresholding to compose a WT-FD filter, for enhanced separation of
      explosive LS (ELS) and BS (EBS) from the background noise. In particular, the WT
      FD filter incorporates the WT-based multiresolution decomposition to initially
      decompose the recorded bioacoustic signal into approximation and detail space in
      the WT domain. Next, the FD of the derived WT coefficients is estimated within a
      sliding window and used to infer where the thresholding of the WT coefficients
      has to happen. This is achieved through a self-adjusted procedure that
      iteratively "peels" the estimated FD signal and isolates its peaks produced by
      the WT coefficients corresponding to ELS or EBS. In this way, two new signals are
      constructed containing the useful and the undesired WT coefficients,
      respectively. By applying WT-based multiresolution reconstruction to these two
      signals, a first version of the desired signal and the background noise is
      provided, accordingly. This procedure is repeated until a stopping criterion is
      met, finally resulting in efficient separation of the ELS or EBS from the
      background noise. The proposed WT-FD filter introduces an alternative way to the
      enhancement of bioacoustic signals, applicable to any separation problem
      involving nonstationary transient signals mixed with uncorrelated stationary
      background noise. The results from the application of the WT-FD filter to real
      bioacoustic data are presented and discussed in an accompanying paper.

PMID- 15977746
TI  - A novel technique for the extraction of fetal ECG using polynomial networks.
AB  - In this paper, we propose a novel technique for extracting fetal
      electrocardiogram (FECG) from a thoracic ECG recording and an abdominal ECG
      recording of a pregnant woman. The polynomial networks technique is used to
      nonlinearly map the thoracic ECG signal to the abdominal ECG signal. The FECG is
      then extracted by subtracting the mapped thoracic ECG from the abdominal ECG
      signal. Visual test results obtained from real ECG signals show that the proposed
      algorithm is capable of reliably extracting the FECG from two leads only. The
      visual quality of the FECG extracted by the proposed technique is found to meet
      or exceed that of published results using other techniques such as the
      independent component analysis.

PMID- 15977747
TI  - Integrating benefits decision making.
AB  - Integrated employee benefit decision making helps employees use their benefits
      more wisely and identify opportunities to balance their immediate benefits needs
      (such as health care) and future benefits needs (such as retirement). This
      article discusses how employers can overcome employees' behavioral barriers to
      making integrated employee benefit decisions by changing the ways benefits are
      communicated and employees are presented with action decisions. Undertaking these
      steps allows employers to not only improve their employees' overall financial
      perspectives, but also furthers plan sponsors' goals of actively promoting
      personal responsibility with respect to retirement funding and changing employee
      behavior with respect to controlling health care costs.

PMID- 15977748
TI  - Communicating total rewards to the generations.
AB  - This is the first time in American history that four distinct generations have
      been in the workforce at the same time. Because employers have finite resources
      with which to compete for talent, they must understand the generations, what
      matters most to them and what they can do to motivate different generations of
      workers. Perhaps surprisingly, the author argues that the generations share in
      most valuing "soft cost" rewards over "hard dollar cost" items. This article
      advises employers on how to make their company a great place to work for all
      generations.

PMID- 15977749
TI  - Health care consumerism: engaging the real buyers--employees.
AB  - Many employers have begun moving toward health care consumerism strategies
      designed to encourage employees to take more responsibility for their health care
      and the cost of that care. Recent surveys suggest ways employers can ensure their
      consumerism strategies succeed in engaging employees and, ultimately, encourage
      employees to change their behavior. This article describes what those surveys
      reveal about employer and employee perspectives on consumerism and suggests steps
      employers can take to align their interests with those of their employees in
      order to manage the demand for and use of health care.

PMID- 15977750
TI  - Understanding the real risks of changing employee benefit plans.
AB  - In an environment of constant change, corporations are looking to alter employee
      benefits programs to make them more responsive to employee and business needs. A
      complete risk assessment process is the key to preparing for changes to employee
      benefits programs by providing employers with an analysis of cost savings against
      the potential negative ramifications of change. This article outlines the steps
      involved in a complete review of risk assessment. It then discusses how employers
      can develop successful change management communication strategies if, after
      conducting a risk assessment, employers decide to move forward with alterations
      to their employee benefits programs.

PMID- 15977751
TI  - Health plans--false enrollment information--standard of review. Shipley v.
      Arkansas Blue Cross and Blue Shield.

PMID- 15977752
TI  - HMOs--financial incentives--disclosure. Horvath v. Keystone Health Plan East,
      Inc.

PMID- 15977753
TI  - Prescription drug copayments--fiduciary duty--plan discounts--disclosure. Alves
      v. Harvard Pilgrim Health Care, Inc.

PMID- 15977754
TI  - Washington loves doctors--or at least their money.

PMID- 15977755
TI  - Collecting just got harder.

PMID- 15977756
TI  - Alonzo brought me back to life.

PMID- 15977757
TI  - EHRs: where are we now?

PMID- 15977758
TI  - What about the VA's EHR.

PMID- 15977759
TI  - Are you getting through?

PMID- 15977760
TI  - Prodding insurers? Use patient power.

PMID- 15977761
TI  - Enlist employers in claim fights.

PMID- 15977762
TI  - 6 steps to better coding.

PMID- 15977763
TI  - When a drug is withdrawn.

PMID- 15977764
TI  - How I'd fix Medicare.

PMID- 15977765
TI  - Can adults with cognitive impairment consent to take part in research?

PMID- 15977766
TI  - Prevention of non-healing wounds through the prediction of chronicity.

PMID- 15977767
TI  - Pressure ulcers and nutrition: a new European guideline.

PMID- 15977768
TI  - Is there enough clinical evidence to use honey to manage wounds?

PMID- 15977769
TI  - Osteomyelitis complicating three types of traumatic hand wound.

PMID- 15977770
TI  - Risk, prevalence and prevention of pressure ulcers in three Swedish healthcare
      settings.
AB  - OBJECTIVE: This cross-sectional survey set out to delineate risk, prevalence and
      prevention of pressure ulcers in a university hospital, a general hospital and a
      nursing home in Sweden. It also looked at the differences in risk factors and
      preventive strategies between patients with and without pressure ulcers. METHOD:
      The one-day survey followed the methodology developed by the European Pressure
      Ulcer Advisory Panel (EPUAP). It was conducted on Tuesday 5 February 2002. Each
      patient was visited by two registered nurses, their skin was inspected and any
      pressure ulcer classified according to the EPUAP grading system. A total of 695
      patients were included: 612 from the university hospital, 38 from the general
      hospital and 45 from the nursing home. RESULTS: The prevalence of pressure ulcers
      was 23.9% (university hospital), 13.2% (general hospital) and 20.0% (nursing
      home). Most (60-66%) of the pressure ulcers in the hospitals were assessed as
      grade I. Only half of the patients at risk or with pressure ulcers were placed on
      a pressure-reducing mattress and a third of these patients had a plan for
      repositioning. Significant variables associated with pressure ulcers were old
      age, geriatric care, low Braden score and incontinence. CONCLUSION: Prevalence of
      pressure ulcers was higher than expected. Results relating to both prevalence of
      pressure ulcers (grade I excluded) and the preventive care given to patients at
      risk or with pressure ulcers accord with those of a larger Dutch study. Attention
      must focus on the appropriate risk-assessment skills, highlighting grade I as
      pressure damage, and the use of appropriate preventive strategies, based on the
      level of risk.

PMID- 15977771
TI  - Factors that affect concordance with compression therapy.

PMID- 15977772
TI  - A small study in healing rates and symptom control using a new sheet hydrogel
      dressing.
AB  - OBJECTIVE: This study set out to investigate the pain control and absorptive
      properties of a new sheet hydrogel dressing (ActiFormCool, Activa). METHOD: This
      was a simple evaluation involving 20 wounds. Compression was used when
      appropriate, although each patient receiving compression had used short-stretch
      bandages before entering the study. RESULTS: Pain was reduced from an average of
      8.65 to an average of 3.75, where 10 represents the worst pain possible and one
      represents no pain. Exudate reduction was assessed by the number of dressing
      changes required each week. The dressing-change rate reduced from an average of
      2.8 times weekly to an average of 1.3 times weekly. Skin condition improved in
      all three cases in which the surrounding skin had been a problem before the
      study. Over a four-week period, two wounds healed, four healed by 90% and two by
      80%, with an overall average healing rate of 46%. CONCLUSION: ActiFormCool
      provides an optimum wound-healing environment, reduces pain and absorbs fluid,
      making it an excellent alternative to loose hydrogels.

PMID- 15977773
TI  - Long-term clinical outcome in patients with severe left ventricular dysfunction
      and an implantable cardioverter-defibrillator after ventricular tachyarrhythmias.
AB  - Left ventricular ejection fraction (LVEF) is accepted as an important prognostic
      marker in patients (pts) with implantable cardioverter-defibrillators (ICD). The
      impact of this therapeutic approach in the survival of pts with life-threatening
      arrhythmias and severe left ventricular dysfunction remains a matter of
      discussion. OBJECTIVE: To evaluate the long-term clinical implications of severe
      left ventricular dysfunction in pts with an ICD implanted for secondary
      prevention of sudden cardiac death (SD). METHODS: Out of 70 pts undergoing ICD
      implantation in our institution over four consecutive years, we studied 24 pts
      with LVEF <35% and a post-ICD follow-up of >12 months (87.5% male; age 62.79
      years). The index arrhythmia was ventricular tachycardia in 19 cases and SD with
      ventricular fibrillation in 5 cases. The underlying disease was ischemic
      cardiomyopathy (n=19), dilated cardiomyopathy (n=4) and hypertensive heart
      disease (n=1). Mean LVEF at the time of implant was 25 +/- 7% (between 11% and
      34%; NYHA class II/III in 83.3%). A du chamber system was implanted in 5 cases,
      and an ICD plus cardiac resynchronization pacing in 2 cases. There was no
      perioperative mortality. At the time of discharge, 71.2% of the pts were taking
      amiodarone and 66.7 % beta-blockers. During a 38 +/- 16-month follow-up (4
      appointments/year), we analyzed the following parameters: rehospitalization for
      cardiovascular cause, appropriate ICD shocks, inappropriate detections/therapy,
      nonfatal major arrhythmic events (arrhythmic storm, therapeutic exhaustion,
      recurrent ventricular tachycardia), cardiac mortality, SD and total mortality.
      RESULTS: Forty-five readmissions (1.9 +/- 2.3/pt) occurred in 14 pts (58%), 24.4%
      due to congestive heart failure. Appropriate ICD shocks (without hospitalization)
      occurred in 62.5% of the pts, 16.6% had inappropriate therapy (50% because of
      increased heart rate due to atrial fibrillation) and 37.5% suffered nonfatal
      major arrhythmic events. Death due to SD was 4.2%, cardiac mortality 12.5% and
      total mortality 25%. CONCLUSIONS: Severe left ventricular dysfunction is common
      in ICD pts. During long-term follow-up, the majority of these pts receive
      appropriate ICD shocks, which emphasizes the importance of SD prevention in this
      population. The frequent documentation of supraventricular arrhythmias (causing
      inappropriate ICD therapy) and nonfatal major arrhythmic events also reflects the
      presence of a worse arrhythmic substrate in this subgroup. Despite the poor
      initial prognosis associated with ventricular tachyarrhythmias in pts with severe
      left ventricular dysfunction, ICD therapy may contribute to a better long-term
      clinical outcome.

PMID- 15977774
TI  - Efficacy of implantable cardioverter-defibrillators: from trials to the real
      world.

PMID- 15977775
TI  - Acute coronary syndrome and depression.
AB  - INTRODUCTION: Clinical depression is associated with poor compliance in risk
      reduction recommendations and has been suggested as an independent risk factor
      for increased postmyocardial infarction morbidity and mortality. AIM: To
      determine the prevalence of depressive symptoms, their main determinants and
      their influence on clinical evolution in acute coronary syndromes (ACS) patients.
      METHODS: We studied depressive symptoms, sociodemographic variables,
      cardiovascular status and therapeutic procedures in 240 consecutive patients
      admitted for ACS. Depressive symptoms were assessed using the Beck Depression
      Inventory (BDI) after clinical stabilization, in patients with more than 4 years'
      education. RESULTS: The majority of the patients were male (203); their average
      age was 59.4 +/- 13 yrs; 31.8% were admitted for unstable angina, 33.1% for acute
      myocardial infarction with ST elevation and 31.8% without ST elevation.
      Depressive symptoms (BDI > or =10) were present in 100 patients (41.6%).
      Depressed patients were older (61.1 vs. 58.2 years, p = 0.06) and had a history
      of previous cardiovascular events /47.5 vs. (34.8% p = 0.05). The proportion of
      female was higher in the group of patients with BDI > or =10 (24% vs. 9.3%, p =
      0.02). Traditional cardiovascular risk factors were not associated with
      depressive symptoms. There were no statistically significant differences between
      the depressed and non-depressed patients in admission diagnosis, in-hospital
      clinical evolution and treatment. There were 35 patients (14.6%) with
      moderate/severe depression (BDI > or =19), 12 of whom were women (OR = 3.8, p =
      0.001); no relation was established between age and previous cardiac events.
      These scores were less frequent in patients with a higher level of education (OR
      = 0.28, p = 0.09) and married (OR = 0.31 vs. not married, p = 0.03). Clinical
      follow-up of 158 patients was achieved (16 +/- 4 months), in patients with BDI >
      or =19, the presence of cardiovascular symptoms (angina, congestive heart
      failure) was higher (46% vs. 23%, OR = 2.8, p = 0.03), even after adjustment for
      age (OR = 2.5; p = 0.06). However, there was no association between the presence
      of depressive symptoms and readmission and/or fatal events. CONCLUSION:
      Depression is a common finding after hospital admission for ACS, particularly in
      women, and is mainly associated with prehospital factors. In our group of
      patients, the presence of depressive symptoms was closely related to clinical
      status during follow-up.

PMID- 15977776
TI  - Deaths from ischemic disease, anthropometry and cardiac biometry.
AB  - INTRODUCTION: The relation between body mass index (BMI)/obesity and left
      ventricular hypertrophy (LVH) in ischemic heart disease (IHD) has not been
      completely established, based on postmortem studies. OBJECTIVE: To study necropsy
      data of deaths from cardiac ischemia and its relation to macroscopic data of the
      heart and anthropometry. METHOD: Retrospective study of necropsies conducted by
      the medical legal services of Porto in 2002-03, with a final diagnosis of
      "myocardial infarction" or "chronic ischemic heart disease" or with more than 50%
      obstructive coronary disease. An observation grid was compiled from the necropsy
      data, with emphasis on anthropometry and cardiac exam. Descriptive and
      inferential methods (Pearson's correlation, the chi-square test and stepwise
      multiple regression) were used for the statistical analysis (alpha = 0.05).
      RESULTS: Of the 231 selected cases, 75.3% were men, of whom 53.7% were diagnosed
      with myocardial infarction and 46.3% with IHD, with BMI of 26.9 +/- 5.1, body
      weight of 74.7 +/- 19.9 kg, left ventricular thickness of 16.9 +/- 4.7 mm, and
      cardiac weight of 517 +/- 163 g. Significant negative correlations (p < 0.001)
      were found between age, body weight (-0.33), height (-0.33), and BMI (-0.21) and
      positive correlations between cardiac weight, body weight (0.35), height (0.24),
      BMI (0.26), and LVH (0.29). Significant differences were found between genders
      with regard to age, weight, height and heart weight, but no differences in terms
      of years of education, BMI or left ventricular thickness. Stepwise regression
      found two predictive variables for heart weight: body weight, accounting for
      12.1%, with age increasing this to 15.4%. CONCLUSION: These results seem to
      confirm objectively by postmortem examination that high values of BMI and body
      weight, left ventricular hypertrophy and cardiac weight correlate with IHD, with
      important gender differences to be taken into consideration. Body weight and age
      are major predictive variables for heart weight. These findings have important
      public health implications in the prevention of overweight and ischemic heart
      disease.

PMID- 15977777
TI  - The potential role of cardiac magnetic resonance imaging in selecting patients
      with ischemic left ventricular dysfunction for the implantation of a cardioverter
      defibrillator.
AB  - OBJECTIVES: To develop a protocol to risk stratify patients before ICD
      implantation in ischemic left ventricular dysfunction using magnetic resonance
      imaging and a gadolinium-based contrast agent. Ejection fraction as determined by
      other methods was reconfirmed using cardiac MRI. METHODS: Five patients
      considered for implantation of an ICD were prospectively offered a cardiac MR
      exam between Novem-ber 2003 and June 2004. All had a history of MI and LV
      dysfunction, had undergone complete coronary revascularization or were considered
      ineligible for revascularization. RESULTS: In three patients the MR ejection
      fractions were less than 30%, confirming the values detected by echocardiography.
      One patient had a larger EF by MRI compared to echo and ICD implantation was
      deferred. One patient thought to have an EF greater than 35% by echo on three
      studies was confirmed to have a much lower EF by MRI and was selected to undergo
      ICD implantation. CONCLUSION: Cardiac MRI can be used to further stratify
      patients selected for an ICD. Ejection fraction can be more reliably estimated by
      MRI and the presence of extensive scar can be detected. The presence of extensive
      scar and a low ejection fraction, which are two factors known to predispose
      patients to sudden cardiac death in ischemic left ventricular dysfunction, can be
      studied reliably by MRI.

PMID- 15977778
TI  - Adolescent and adult congenital heart disease assessed by real-time three
      dimensional echocardiography: an initial experience.
AB  - Real-time three-dimensional (3D) echocardiography has enormous diagnostic
      potential, enabling acquisition of full-volume three-dimensional images in real
      time, which can be sliced in several planes and rotated in order to achieve a
      more accurate study of the target cardiac structures. It is particularly useful
      because it enables the heart to be visualized from multiple perspectives in the
      same way a surgeon would see it during an operation. We describe our
      echocardiographic laboratory's experience with real-time 3D ultrasound study of
      adolescent and adult congenital heart disease.

PMID- 15977779
TI  - Are degenerative changes in the aortic valve an additional important marker of
      atherosclerosis?
AB  - BACKGROUND AND AIM: Degenerative changes of the mitral annulus are associated
      with atherosclerotic disease. It has recently been suggested that degenerative
      changes in the aortic valve may also be associated with atherosclerosis. The
      intima-media thickness of the carotid arteries has been used as one of the best
      and earliest markers of atherosclerosis. The aim of this study was to evaluate
      whether the additional presence of degenerative changes in the aortic valve in
      coronary patients with mitral annular degenerative disease reflects different
      degrees of intima-media thickness as assessed by carotid ultrasonography.
      METHODS: The study group included 55 patients admitted for myocardial infarction
      who presented with degenerative changes of the mitral annulus assessed by
      echocardiography. Exclusion criteria were moderate or severe valvular heart
      disease and chronic renal failure. All patients underwent echocardiography,
      cardiac Doppler and carotid ultrasonography. Based on the echocardiographic
      findings, two sub-groups were formed: 1--with degenerative changes of the aortic
      valve; and 2--without degenerative changes of the aortic valve. Carotid
      ultrasonography was performed with a 7.5-10 MHz linear transducer and the
      following parameters were evaluated: 1--bilateral measurement of intima-media
      thickness in the common carotid artery; 2-- incidence of atheromatous plaques in
      the carotid arteries, and 3--incidence of >50% lesion in the internal carotid
      arteries assessed by pulsed Doppler (Vmax >125 cm/s). RESULTS: Thirty-three
      patients (aged 71.6 +/- 7.1 years), 21 men and 12 women, did not present
      degenerative changes in the aortic valve. The other group consisted of 22
      individuals (aged 72.9 +/- 6.8 years), 14 men and 8 women, who did have such
      changes. Differences in age and gender distribution between the two groups were
      not significant. Patients with degenerative aortic valve disease had greater
      intima-media thickness than the control group (1.6 +/- 0.3 mm versus 1.3 +/- 0.4
      mm, p < 0.001). Fifteen (68%) patients with aortic degenerative disease had
      plaques in the carotid arteries compared to 11 (33%) patients in the control
      group (p < 0.05). No significant differences were found between the two groups
      regarding the incidence of >50% atherosclerotic lesion in the internal carotid
      artery (22% versus 12%; NS). CONCLUSIONS: Patients with degenerative changes in
      the aortic valve presented significantly greater intima-media thickness and a
      higher incidence of atherosclerotic plaques than the control group, suggesting
      that their presence may constitute an additional important marker of severity of
      atherosclerotic disease.

PMID- 15977780
TI  - Intracranial aneurysms as the first sign of coarctation of the aorta.
AB  - The case of a twenty-seven-year old man with coarctation of the aorta who
      suffered rupture of cerebral aneurysms is presented. Treatment was successful for
      both lesions.

PMID- 15977781
TI  - [Acute aortic dissection].
AB  - Acute aortic dissection is a relatively common pathology, which is related to the
      high incidence of arterial hypertension observed in some population subgroups. It
      is accompanied by a high mortality rate if not treated immediately. Early
      diagnosis is relatively simple but depends on a high index of suspicion. Its
      etiopathogenesis is related to cystic medial necrosis. In the majority of cases,
      the aortic wall is abnormal along its entire length. Surgery is indicated in
      virtually all type A dissections, with involvement of the ascending aorta, and in
      many type B dissections, characterized by isolated involvement of the descending
      aorta. In the majority of the latter, however, medical therapy appears to lead to
      better results than surgery, but in recent times, treatment has been
      revolutionized by the use of stents. Surgery is rarely curative. Hence, long-term
      follow-up (probably for life) is essential. This includes strict control of
      arterial hypertension and monitoring of the untreated aortic segments, and
      especially any residual patent false lumen, which is observed in the majority of
      cases, in order to prevent rupture and to minimize the consequences of the
      formation of false aneurysms.

PMID- 15977782
TI  - Critical appraisal of clinical studies: practical tables.

PMID- 15977783
TI  - 2003 Portuguese Pacing Registry.

PMID- 15977784
TI  - The use of mutislice computed tomography in assessment of the coronary arteries
      in Kawasaki disease.

PMID- 15977786
TI  - [Proteinase inhibitors and their function in plants: a review].
AB  - The spread, classifications, and properties of plant proteins capable of
      inhibiting proteinases have been reviewed. Data from the literature on the likely
      physiological functions of these inhibitors in plants are analyzed.

PMID- 15977787
TI  - [Enzymatic synthesis of a conducting complex of polyaniline and poly(2-arcylamido
      2-methyl-1-propanesulfonic ACID) using palm tree peroxidase and its properties].
AB  - An enzymatic method of producing a conducting polyelectrolyte complex of
      polyaniline (PANI) and poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS)
      was developed. Acidic stable peroxidase isolated from royal palm tree (Roystonea
      regia L.) leaves was used as a catalyst in the oxidative polymerization of
      aniline at pH 2.8. The synthesis procedure was optimized. Spectroscopic and
      electrochemical characteristics of nanoparticles of obtained PANI/PAMPS complexes
      at different pH were studied. It was shown that the acidity of the medium affects
      their properties.

PMID- 15977788
TI  - [Activity of polygalacturonase-inhibiting protein of banana fruit tissues].
AB  - The activity of polygalacturonase and the protein inhibiting this enzyme, which
      affected polygalacturonases of phytopathogenic fungi Verticillium dahliae and
      Gloesporium musarium, were detected in banana (Musa acumthata L.) fruit of
      cultivars Cavendish and Korolevskii. The polygalacturonase from banana fruit was
      inhibited by the preparations of the protein inhibitor not only from bananas but
      also from potato (Solanum tuberosum L.) tubers and pepper (Capsicum annuum L.)
      fruit.

PMID- 15977789
TI  - [Properties of nitrate reductase from Fusarium oxysporum 11dn1 fungi grown under
      aerobic and anaerobic conditions].
AB  - Production of nitrate reductase was studied in 15 species of microscopic fungi
      grown on a nitrate-containing medium. Experiments were performed with Fusarium
      oxysporum 11dn1, a fungus capable of producing nitrous oxide as the end product
      of denitrification. Moreover, a shift from aerobic to anaerobic conditions of
      growth was accompanied by a sharp increase in the activity of nitrate reductase.
      Studies of nitrate reductase from the mycelium of Fusarium oxysporum 11dn1, grown
      under aerobic and anaerobic conditions, showed that this enzyme belongs to
      molybdenum-containing nitrate reductases. The enzymes under study differed in the
      molecular weight, temperature optimum, and other properties. Nitrate reductase
      from the mycelium grown under aerobic conditions was shown to belong to the class
      of assimilatory enzymes. However, nitrate reductase from the mycelium grown
      anaerobically had a dissimilatory function. An increase in the activity of
      dissimilatory nitrate reductase, observed under anaerobic conditions, was
      associated with de novo synthesis of the enzyme.

PMID- 15977790
TI  - [Metabolic pathways responsible for consumption of aromatic hydrocarbons by
      microbial associations: molecular-genetic characterization].
AB  - Genes for catechol 1,2- and 2,3-dioxygenases were cloned. These enzymes hold
      important positions in the ortho and meta pathways of the metabolism of aromatic
      carbons by microbial associations that consume the following volatile organic
      compounds in pilot minireactors: toluene, styrene, ethyl benzene, o-xylene, m
      xylene, and naphthalene. Genes of both pathways were found in an association
      consuming m-xylene; only genes of the ortho pathway were found in associations
      consuming o-xylene, styrene, and ethyl benzene, and only genes of the meta
      pathway were found in associations consuming naphthalene and toluene. Genes of
      the ortho pathway (C120) cloned from associations consuming o-xylene and ethyl
      benzene were similar to corresponding genes located on the pND6 plasmid of
      Pseudomonas putida. Genes of the ortho pathway from associations consuming o
      xylene and m-xylene were similar to chromosomal genes of P. putida. Genes of the
      meta pathway (C230) from associations consuming toluene and naphthalene were
      similar to corresponding genes formerly found in plasmids pWWO and pTOL.

PMID- 15977791
TI  - [NP-detecting DNA technologies: solving problems of applied biochemistry].
AB  - Heterozygosity of CANP3, ACTN3, and GHR genes in specialized collections was
      studied using state-of-the-art DNA technologies for DNA analysis. A new
      dinucleotide deletion (AC) at the beginning of exon 21 was identified in five
      individuals with heterozygous CANP3 gene. Analysis of polymorphism (SNP1747 C-
      >T) of ACTN3 gene demonstrated a positive association of allele C with a high
      muscular performance. Real-time PCR assay of SNP1630 (A-->C) in GHR gene
      suggested a putative negative association of allele C of this SNP with a high
      muscular performance.

PMID- 15977792
TI  - [R-phycoerythrin: a natural ligand for detoxifying cadmium ions and a tunnel
      matrix for synthesis of cadmium sulfide nanoparticles].
AB  - As evidenced by ion-selective electrode potentiometry, the hexameric R
      phycoerythrin (RPE) molecule binds 20-4000 cadmium ions (Cd2+) depending on Cd2+
      concentration in the solution. Cadmium ions bound to RPE serve as nuclei of
      cadmium sulfide crystallization in the presence of sulfide ions. According to
      spectrometric, electron-microscopic and capillary electrophoresis data, the
      particles are heteroaggregates of 3.2 x 6 nm in size. The fact that the particle
      size fits the size of the central tunnel of the RPE molecule and the similarity
      between the electrophoretic patterns of free RPE and the RPE-CdS complex indicate
      that the tunnel space, limiting the crystal growth, is the most probable site of
      nanoparticle formation. Properties of the nanoparticles can be modified by
      changing temperature, pH, etc. It is concluded that RPE can be used as a reagent
      for detoxification of cadmium ions and a matrix for synthesis of elongated CdS
      nanoparticles.

PMID- 15977793
TI  - [Tolerance of 5,10-methenyltetrahydrofolate to ultraviolet radiation].
AB  - Aeration of aqueous solutions of 5,10-methenyltetrahydrofolic acid (MTHF) during
      exposure to ultraviolet irradiation (lambda 300-390 nm, 240 W/m2, 30 min) slowed
      down photolysis in comparison with deaerated solutions. The rate of photolysis in
      the presence of oxygen depended on buffer composition. It did not exceed 6% of
      the starting amount of MTHF. Photolysis of MTHF included opening of the
      imidazoline ring, dehydrogenation of the tetrahydropterin portion, and
      elimination of the p-aminobenzoylglutamate moiety. 6,7-Dimethyltetrahydropterin
      was used as a model compound to show that protonation of the reduced pterin
      heterocycle increased its tolerance to oxidation, and UV irradiation did not
      accelerate this process. The stabilizing effect of protonation of the pterin
      portion and the presence of the positively charged imidazoline moiety are assumed
      to hamper MTHF oxidation and photolysis. It is assumed that these factors favored
      the choice of MTHF molecules as photosensors in light-sensitive proteins in the
      course of evolution.

PMID- 15977794
TI  - [Study of galactoglucomannans from the seed of Cercis canadensis L].
AB  - Galactoglucomannans were isolated by selective precipitation from aqueous and
      alkaline extracts of endosperm and hulls of Cercis canadensis, a member of the
      family Fabaceae. Their monosaccharide composition (Man: Gal: Glu) was as follows:
      10.4: 0.9: 1 (polysaccharide from the endosperm) and 4.5: 0.9: 1 (polysaccharide
      from the hulls). The identity of IR spectra was indicative of the commonness of
      their structure. Analysis of the structure of the galactoglucomannan from
      endosperm by 13C NMR spectroscopy showed that its main chain consisted of 1,4
      beta-D-manno- and 1,4-beta-D-glucopyranose. Part of mannose residues in the chain
      were substituted at C6 with single residues of alpha-D-galactopyranose.
      Galactoglucomannans are located in different part of the seed and implement
      different functions.

PMID- 15977795
TI  - [Ultramorphometric study of the plastids in apical tuber cells of original and
      transgenic potato plants treated with ambiol].
AB  - Ultramorphometric characteristics of plastids in cells of apical tuber meristems
      of original and defensin gene-transfected potato (Solanum tuberosum L.) plants,
      either maintained under normal conditions or subjected to treatment with the
      antioxidant ambiol, were compared. Under normal conditions, the tuber cells of
      the original and transgenic potato plants differed in neither the number nor size
      of the plastids. Only certain quantitative distinctions in the development of
      individual ultrastructural characteristics of plastids were detected. Treatment
      with ambiol enhanced the differentiation of the internal membrane system of
      plastids in the cells of original and transgenic plants, especially the tubular
      membrane systems. Certain differences in the responses to ambiol of cell plastids
      of original and transgenic plants were related to plastid sizes and development
      of individual intraplastid structures. The results comply with earlier data on
      varying responses of mitochondria of original and transgenic plants to ambiol
      treatment.

PMID- 15977796
TI  - [Role of elements and physiologically active compounds in the regulation of
      synthesis and accumulation of indole alkaloids in Catharanthus roseus L].
AB  - Effects of various elements (Co, Ni, Zn, W, Mn, Cr, B, Mo, Fe, and V), natural
      and synthetic auxins, cytokinins, and gibberellin on biosynthesis and
      accumulation of indole alkaloids was studied at increasing concentrations in the
      model system of Madagascar periwinkle seedlings (Catharanthus roseus L.). The
      main types of concentration dependences for the effect of physiologically active
      compounds under study were evaluated. A possible mechanism of the influence of Zn
      and auxin on this process was partly clarified. The compounds were shown to
      modulate various stages in the biosynthesis of monomeric indole alkaloids
      (catharanthine and vindoline).

PMID- 15977797
TI  - [Adaptogenic effects of furostanol glycosides of Dioscorea deltoidea wall on
      oxidative processes in tomato plants in biotic stress].
AB  - The effect of furostanol glycosides of cell culture of Dioscorea deltoidea Wall
      on oxidative processes in tomato plants subjected to invasion with the gall
      nematode Meloidogyne incognita Kofoid et White was studied. We showed that
      furostanol glycosides induce a nonspecific defensive response in plants. Exposure
      of cell membranes to furostanol glycosides cause rearrangements in fatty acids
      resulting in the formation of conjugated dienes, which makes molecules
      thermodynamically more stable under stress conditions. The study of changes in
      the activity of peroxidases of intact plants and plants affected with the
      nematode, which were treated with furostanol glycosides, showed that the
      protective effect of the guaiacol-dependent peroxidase is more long-term than the
      effect of the benzidine-dependent peroxidase.

PMID- 15977798
TI  - [Free and conjugated forms of salicylic acid: content and role in potato].
AB  - Hydrolysis of conjugated forms of salicylic acid and accumulation of its free
      form was observed after infection of potato tubers (Solanum tuberosum L.) with an
      incompatible race of phytophthora or treatment with an elicitor (chitosan).
      Infection of tubers with a compatible race of the pathogen or treatment with a
      suppressor (laminarin) decreased both the degree of hydrolysis of conjugated
      forms of salicylic acid and the accumulation of its free form.

PMID- 15977799
TI  - [The role of plastids and assimilate transport system in the control of plant
      development].
AB  - Phylogenetic and ontogenetic relationships between the plastids, cell endoplasmic
      reticulum, and plant transport communication have been reviewed. The initiating
      role of plastids (endosymbionts) in the origin of endoplasmic reticulum (buffer
      zone of endosymbiogenesis) has been shown, as well as a similar role of
      endoplasmic reticulum in the development of transport communication of xylem and
      phloem. Plastids, sugars and transport system for their distribution can be
      interpreted as leading sections in the mechanism of developmental control: gene
      expression of nuclear genome and genome of organelles, cell and tissue
      differentiation, and plant morphogenesis. The conflict between the bulk of plant
      genome and low percentage of its realization is explained as a result of
      limitation of the nuclear genome realization by plastid genome. The concept of
      development as applied to plant ontogenesis has been critically analyzed. The
      possibilities of the concept correction by with the help of symbiogenetic
      hypothesis are discussed.

PMID- 15977800
TI  - [Evolutionary reorganizations of ontogenesis in sea urchins].
AB  - The data published during recent 15-20 years on comparative, experimental and
      molecular embryology of unusually developing sea urchins have been reviewed.
      These animals are characterized by large lipidrich eggs, highly modified
      embryogenesis, and the absence of a planktotrophic larva. Such a type of
      development is evolutionary advanced and arose independently in various
      phylogenetic lineages of the sea urchins.

PMID- 15977801
TI  - [Specific features of centriole formation and ciliogenesis in ciliary epithelium
      cells of respiratory tracts in patients with Kartagener syndrome].
AB  - An electron microscopic study of the ciliary epithelium of respiratory tracts was
      carried out in children (members of the same family) with Kartagener syndrome,
      which is a variant of ciliary dyskinesia. It was shown that in the case of both
      mobile cilia and ciliary dyskinesia in man, centrioles are formed during
      formation of the ciliary basal bodies predominantly de novo, involving
      deuterosomes. A wide spectrum of pathological changes was described in
      literature, such as the absence of dynein arms in the axoneme and disorganization
      of axoneme structure. In addition to these changes in the ciliary system, we
      found integration of several ciliary axonemes by the same plasma membrane,
      running of microtubules from the plasma membrane as bundles, different
      orientation of basal legs, etc.

PMID- 15977802
TI  - [Effects of guanine nucleotides and protein kinase C on prolactin-stimulated
      release of Ca from intracellular stores of pig oocytes].
AB  - The effects of guanine nucleotides and protein kinase C on prolactin-stimulated
      Ca2+ release from intracellular stores of pig oocytes were studied using the
      fluorescent dye chlorotetracycline. The effect of prolactin was related to the
      protein kinase C activation. Inhibition of protein kinase C stimulated Ca2+
      release from intracellular stores of the pig oocytes treated with 5 ng/ml
      prolactin in the presence of extracellular Ca2+ and inhibited Ca2+ release from
      intracellular stores of the pig oocytes treated with 50 ng/ml prolactin. In a
      Ca2+-free medium, prolactin did not stimulate Ca2+ release from intracellular
      stores of the oocytes treated with GDP in the presence of GDP. GTP inhibition of
      protein kinase C activated Ca2+ release from intracellular stores of the pig
      oocytes treated with 5 ng/ml prolactin and inhibited Ca2+ release from
      intracellular stores of the pig oocytes treated with 50 ng/ml prolactin. These
      data suggest the influence of guanine nucleotides and protein kinase C on calcium
      metabolism, stimulated by prolactin.

PMID- 15977803
TI  - [Changes in proteasome activity and subunit composition during postnatal
      development of rat].
AB  - The dynamics of the activities of 26S and 20S proteasomes in the rat liver and
      spleen have been studied during postnatal development from 1 to 90 days. The
      activities of proteasome forms both in spleen and in liver increased in adult
      animals as compared to one day rats. The activities of both proteasome forms in
      the liver did not differ significantly from those in the spleen at all stages of
      postnatal development. Using Western blot with monoclonal antibodies to Rpt6
      subunit, we confirmed the presence of 26S proteasome in both organs at all stages
      of postnatal development. Studies with polyclonal antibodies to beta1i (LMP2)
      subunit showed the appearance of the immune subunit in the spleen by day 9 and in
      the liver only by day 23 of postnatal development. This result suggests the
      earlier formation of the spleen as an organ with immune functions.

PMID- 15977804
TI  - [Dynamics and variability of early morphogenesis in the loach according to
      observations of individual developmental trajectories].
AB  - The dynamics and variability of quantitative morphological characters
      (morphological variables), which undergo changes upon epiboly, were studied by
      means of vital observations and measurements of developing loach (Misgurnus
      fossilis L.) embryos within equal time intervals. None of morphological
      variables, which characterize the dynamics of blastoderm shape, had monotonous
      dependence on time. In each individual embryo, the intervals of changes in
      morphological variables in the "normal" direction corresponding to the change of
      their mean values during the normal course of epiboly alternated with arrests, as
      well as with the changes of morphological variables in the reverse direction. The
      dynamics of morphological variables in time, which reflect the sequence of
      morphological states of the same embryo, and those of individual variations
      (variations of morphological states of different embryos on the same temporal
      section) had identical structure. This suggests instability of individual
      trajectories of morphogenesis or, strictly speaking, their actual absence. It was
      shown for the first time on the basis of analysis of individual trajectories of
      morphogenesis that its dynamics corresponded to so-called "determined chaos",
      which was previously discussed only as a theoretical possibility. The data
      obtained suggest that upon approach to the equatorial area of the embryo, the
      blastoderm marginal zone was elongated in the longitudinal direction and
      contracted across the axis of its movement. As a result, a positive feedback
      arises between the cooperated cell movement and the change of shape of the
      surface, over which the cells move. This leads, due to unstable radial symmetry
      of this movement, to the formation of embryonic shield.

PMID- 15977805
TI  - [Identification of the gene whose mutation leads to the appearance of recessive
      lethal germlings in Arabidopsis thaliana].
AB  - The data are presented on genetic and molecular-genetic analysis of a mutant from
      the collection of morphological insertion mutants of Arabidopsis thaliana we
      obtained earlier, which belongs to the phenotypic class of recessive lethal
      germlings. A nucleotide DNA sequence, 147 bp in size, was identified, which
      adheres to the left border area of T-DNA insertion. The site of localization of
      the insertion was determined using computer analysis.

PMID- 15977807
TI  - [Libraries of large-insert genomic clones as a tool for molecular cytogenetic
      analysis of avian genome].
AB  - Integration of molecular and cytegenetic levels of investigation results in
      complex understanding of structural and functional genome organization. Gridded
      libraries of large-insert genomic clones represent a powerful tool of the genome
      analysis. Their utilization provides coordination of data on molecular
      organization of nucleic acids with cytogenetic data on the chromosome structure.
      These libraries played an important role in sequencing of genomes of human,
      mouse, and other organisms as an instrument linking molecular biological and
      cytogenetic data via construction of contigs and their localization on the
      chromosomes. They also enabled analysis of orthology between the mammalian
      genomes. The existing avian libraries fit molecular cytogenetic analysis of the
      class Aves genome, and can be successfully used for the isolation and
      characterization of large genomic fragments. This provides utilization of these
      libraries not only for the chromosome mapping, but also for positional cloning
      and search for candidate genes for quantitative traits.

PMID- 15977806
TI  - [15th Congress of International Society of Problems of Nervous System
      Development].

PMID- 15977808
TI  - [Nuclear rDNA variability in laboratory strains of the German cockroach Blattella
      germanica L. (Blattellidae)].
AB  - The polymorphism of nuclear ribosomal DNA has been studied in male German
      cockroaches. The RFLP analysis has been used to identify seven types of HindIII
      fragments, the variation of which may serve as the basis for the differentiation
      of laboratory strains with respect to some population indices, including the
      average number of fragments per animal (N), the proportion of polymorphic loci
      (P), and the average pairwise similarity (APS). The interpopulation variation
      (FST) calculated for nine haplotypes is 53.85%.

PMID- 15977809
TI  - [The use of PCR for detecting genes that encode type I polyketide synthases in
      genomes of actinomycetes].
AB  - PCR screening of type I polyketidesynthase genes (PKS) was conducted in genomes
      of actinomycetes, producers of antibiotics. Some DNA fragments from the
      Streptomyces globisporus 1912 strain, a producer of a novel angucycline
      antibiotic landomycin E, were amplified. These fragments shared appreciable
      homology with type I PKS controlling the biosynthesis of polyene antibiotics
      (pymaricin and nistatin). The cloned regions were used to inactivate putative
      type I PKS genes in S. globisporus 1912. Strains with inactivated genes of PKS
      module do not differ from the original strain in the spectrum of synthesized
      polyketides. Apparently, these are silent genes, which require specific induction
      for their expression. The method of PCR screening can be used in a large-scale
      search for producers of new antibiotics.

PMID- 15977810
TI  - [Conjugative transfer of the large plasmid p19 in various Bacillus subtilis
      strains].
AB  - Cryptic conjugative plasmid p19 from the environmental Bacillus subtilis strain
      19 was labeled with the cat gene conferring resistance to chloramphenicol. The
      resulting plasmid, p19cat, was used to estimate the transfer frequency, to study
      the dynamics of plasmid transfer, and to detect some specific features of
      conjugation between various B. subtilis strains.

PMID- 15977811
TI  - [Quasi-adaptive response to alkylating agents in Escherichia coli: a new
      phenomenon].
AB  - An original hypothesis of a quasi-adaptive response to nitrosomethylurea (NMU) in
      Escherichia coli cells was verified experimentally. In contrast to the true Ada
      response, which is induced in cells pretreated with a sublethal dose of NMU, a
      quasi-adaptive response was induced using NO-containing dinitrosyl iron complex
      with glutathione (DNICglu). Quasi-adaptation increased expression of the Ada
      regulon and cell resistance to the cytotoxic and mutagenic effects of NMU. The
      levels of alkA, alkB, and aidB gene expression in quasi-adaptation were higher
      than in the true Ada response. Thus, experimental evidence was obtained for the
      alternative mechanism regulating the function of the Ada sensory protein in
      controlling expression of the Ada regulon during the adaptive response. The free
      iron--chelating agent o-phenanthroline (OP) facilitated degradation of DNICglu
      (by electron paramagnetic resonance (EPR) spectra) and considerably or completely
      inhibited gene expression in the quasi-adaptive response. The new phenomenon
      extends the functional range of NO compounds to include a role in genetic signal
      transduction within the Ada response system in addition to similar roles in the
      SoxRS, SOS, and OxyR systems in E. coli.

PMID- 15977812
TI  - [Inheritance features of mating behavior components in Drosophila melanogaster
      and their significance for fitness].
AB  - Components of mating behavior of Drosophila melanogaster mutant and wild-type
      strains were studied with respect to fitness. The magnitude of the effect of
      genotype on the male mating activity, female sexual receptivity, fertility and
      viability was determined. Strong positive correlation was found between the male
      mating activity and fitness components. It was shown that mating of strains
      contrasting in sexual behavior features can be accompanied by both heterosis and
      maternal effect. Inheritance coefficients were determined for sexual behavior
      components.

PMID- 15977813
TI  - [The effect of male mating competitiveness, developmental rate, and viability of
      larvae and pupae in Drosophila melanogaster heterozygous for the temperature
      sensitive lethal mutation l(2)M167DTS on the dynamics of the mutation elimination
      from the population].
AB  - The dependence of selection on an introduced mutation 1(2)M167DTS on male mating
      competitiveness, viability, and developmental rate of larvae and pupae of
      Drosophila melanogaster, heterozygous for this mutation, was examined in
      population experiments with preset conditions. The limitations of fitness
      parameters of individuals l(2)M167DTS/+ relative to individuals +/+ were
      estimated according to the conditions of the experiment and phenotypic
      characteristics of the mutation studied. Under conditions of limited food supply
      and dependence on emergence time in each generation, the sequence of female
      mating was shown to be of less importance than the order of medium utilization by
      the progeny of a certain genotype related to the male success in the first
      mating. The limiting factors acting on the l(2)M167DTS mutation were viability
      and developmental rate.

PMID- 15977814
TI  - [Differentiation of Dolly Varden char Salvelinus malma from Asia and North
      America inferred from PCR-RFLP analysis of mitochondrial DNA].
AB  - Genetic differentiation of Dolly Varden char Salvelinus malma Walbaum from the
      Asian and North American Pacific coasts was studied. We examined restriction
      fragment length polymorphism of three mitochondrial DNA (mtDNA) fragments
      amplified in polymerase chain reaction, which encoded four NADH dehydrogenase
      subunits, the cytochrome b gene, and a D-loop segment. The mtDNA haplotypes were
      shown to form three phylogenetic groups, whose geographic distribution
      corresponded to three Dolly Varden subspecies: S. malma malma, S. malma
      krascheninnikovi, and S. malma lordi. The nucleotide sequence divergence between
      S. malma malma and S. malma krascheninnikovi was 3.8%; between S. malma malma and
      S. malma lordi, 3.1%; and between S. malma krascheninnikovi and S. malma lordi,
      2.5%. The northern Dolly Varden S. malma malma from Asia was shown to be
      genetically identical to that from North America.

PMID- 15977815
TI  - [The effect of reproduction biotopes on the genetic differentiation of
      populations of sockeye salmon Oncorhynchus nerka].
AB  - Variation of mitochondrial DNA (mtDNA) was examined in nine populations from
      three lake-river systems of Chukotka and Kamchatka. Significant differences were
      found between most of the sockeye salmon samples studied. The genetic differences
      among populations were not high and often did not correlate with the geographical
      distances between them. The low population divergence is explained by a short
      time of existence of most of them, having been formed after the recession of the
      upper Pleistocene glacier. When the populations were grouped according to their
      spawning biotopes (river or lake), they in general appeared more genetically
      similar than upon their grouping by geographical location (the lake-river
      systems). The differences between the river and lake populations in the lake-
      river systems increased from north to south.

PMID- 15977816
TI  - [Genomic structure of the autotetraploid oat species Avena macrostachya inferred
      from comparative analysis of the ITS1 and ITS2 sequences: on the oat karyotype
      evolution during the early stages of the Avena species divergence].
AB  - To examine the genomic structure of Avena macrostachya, internal transcribed
      spacers, ITS1 and ITS2, as well as nuclear 5.8S tRNA genes from three oat species
      with AsAs karyotype (A. wiestii, A. hirtula, and A. atlantica), and those from A.
      longiglumis (AlAl), A. canariensis (AcAc), A. ventricosa (CvCv), A. pilosa, and
      A. clauda (CpCp) were sequenced. All species of the genus Avena examined
      represented a monophyletic group (bootstrap index = 98), within which two
      branches, i.e., species with A- and C-genomes, were distinguished (bootstrap
      indices = 100). The subject of our study, A. macrostachya, albeit belonging to
      the phylogenetic branch of C-genome oat species (karyotype with submetacentic and
      subacrocentric chromosomes), has preserved an isobrachyal karyotype, (i.e., that
      containing metacentric chromosomes), probably typical of the common Avena
      ancestor. It was suggested to classify the A. macrostachya genome as a specific
      form of C-genome, Cm-genome. Among the species from other genera studied,
      Arrhenatherum elatius was found to be the closest to Avena in ITS1 and ITS
      structure. Phylogenetic relationships between Avena and Helictotrichon remain
      intriguingly uncertain. The HPR389153 sequence from H. pratense genome was
      closest to the ITS1 sequences specific to the Avena A-genomes (p-distance =
      0.0237), while the differences of this sequence from the ITS1 of A. macrostachya
      reached 0.1221. On the other hand, HAD389117 from H. adsurgens was close to the
      ITS1 specific to Avena C-genomes (p-distance = 0.0189), while its differences
      from the A-genome specific ITS1 sequences reached 0.1221. It seems likely that
      the appearance of highly polyploid (2n = 12-21x) species of H. pratense and H.
      adsurgens could be associated with interspecific hybridization involving
      Mediterranean oat species carrying A- and C-genomes. A hypothesis on the pathways
      of Avena chromosomes evolution during the early stages the oat species divergence
      is proposed.

PMID- 15977817
TI  - [dw2, a new mutation of beet Beta vulgaris L].
AB  - Twelve dwarf plants were found in the second hybrid generation of beet. The
      average height of mutant plants was 21.8 cm, their leaf blades and flowers were
      significantly smaller than normal, and the plants exhibited male and female
      sterility. This dwarfism was shown to be caused by a mutation differing from that
      previously described in beet, which is named dwarf2 (dw2). The experimental
      evidence suggests that this mutation appeared in one of the first-generation
      plants. Based on plant phenotype in the first hybrid generation and the number of
      mutant plants in the second one, this mutation is suggested to be under recessive
      monogenic control of the dw2 gene. The genotypic class segregation in the second
      hybrid generation indicates that the dw2 gene is inherited independently of genes
      m, at, and ap that control choricarpousness, gene male sterility, and pollen
      grain aggregation into tetrads.

PMID- 15977818
TI  - [Expression of the symbiotic nod4 pea gene against various genotypic
      backgrounds].
AB  - Experiments on the effect of genotypic environment on the expression of the nod4
      gene, responsible for supernodulation in pea, were performed. The genotypic
      background was found to affect the manifestation of both major symbiosis-related
      traits (number of nitrogen-fixing bacterial nodules and nitrogenase activity) and
      productivity-related traits (stem height, seed number, and seed weight), which
      form the pleiotropic complex of the mutant gene. Using recurrent selection, we
      developed supernodulating lines significantly exceeding the original mutant line
      and studied them up to generations F5-F6. Of special importance is the fact that
      these lines showed high levels of nodulation and nitrogen fixation. The results
      are discussed from the viewpoint of breeding.

PMID- 15977819
TI  - [Characterization of developmental changes in energy metabolism of fiber flax in
      heterosis].
AB  - The contents of adenine nucleotides and nicotinamide coenzymes, along with
      morphological traits, were studied in fiber flax cultivars and F1 hybrids at
      various ontogenetic stages. The energy parameters of heterotic hybrids proved to
      be significantly higher than in the parental cultivars, suggesting a higher
      activity of energy-producing processes determining the intensity of plant growth
      and development. The character of the heterosis effect on morphological, energy,
      and productivity parameters was characterized in the F1 hybrids varying in the
      extent of heterosis. Hybrids that displayed positive dominance or superdominance
      in productivity parameters showed heterosis for most energy parameters.

PMID- 15977820
TI  - [On antimutagenesis mechanism in plants].
AB  - The effect of nitrosylmethylurea (NMU) on the mitotic index and the frequency of
      cells with aberrations, as well as the effects of pre- and posttreatment with
      antioxidant ambiol on the NMU effects were studied on seedlings of common winter
      wheat Triticum aestivum, cultivar Moskovskaya 39. Both pre- and posttreatment
      with ambiol resulted in antimutagenic effect but after posttreatment, the effect
      was lower. Irrespective of type of seedling treatment with ambiol and the time of
      their fixation (45, 48, and 51 h), when mitotic index is plotted versus frequency
      of cells with aberrations, all experimental points fall on the same regression
      line with coefficient of correlation of -0.82 (P < 0.001). This implies that the
      same mechanism underlies antimutagenic effect irrespective of when the
      antimutagen was applied, before or after the knockout mutagen dose. This also
      suggests that the antimutagenic effect is independent of the degree of the
      mutagen-induced damage, because by the time of posttreatment, the volume of
      genome damage is already determined and the antimutagen fails to change it.
      Finally, this suggests that irrespective of time of antimutagen treatment, the
      mutation frequency is reduced by the mechanism of stimulated repopulation.

PMID- 15977821
TI  - [Effective size of the early-run sockeye salmon Oncorhynchus nerka population of
      Lake Azabach'e, Kamchatka Peninsula evaluation of the effect of interaction
      between subpopulations within a subdivided population].
AB  - The effect of subdivision on the effective size (Ne) of the early-run sockeye
      salmon Oncorhynchus nerka population of Lake Azabach'e (Kamchatka Peninsula) has
      been studied. The mode of this effect is determined by the relative productivity
      of the subpopulations and its magnitude, by the rate of individual migration
      among subpopulations and genetic differentiation. If the contributions of
      subpopulations (offspring numbers) are different, genetic differentiation can
      reduce the Ne of the subdivided population. At equal subpopulation contributions,
      genetic differentiation always increases the Ne of the subdivided population in
      comparison with a panmictic population. We have found that all sockeye salmon
      subpopulations of Azabach'e Lake produce equal offspring numbers contributing to
      the next generation. The genetic differentiation between sockeye salmon
      subpopulations is low, and the subdivision increases the Ne of the early-run race
      with reference to the sum of the effective sizes of the subpopulations by as
      little as 2%.

PMID- 15977822
TI  - [Spatial characteristics of marriage migration in the Belgorod population].
AB  - Data from marriage records of the city of Belgorod for 1960, 1985, and 1995 have
      been used to calculate parameters characterizing migration in the Belgorod
      population. The marriage migration coefficients (m) in these years were 0.83,
      0.68, and 0.58, respectively, and the endogamy indices were 0.05, 0.13, and 0.22,
      respectively. The marriage convergence (K) with respect to birthplace in the same
      years were 0.15, 0.13, and 0.14, respectively. In the period studied, spatial
      parameters reflecting the genetic efficiency of migration increased. The mean
      migration distance also increased; it was 430, 667, and 926 km in 1960, 1985, and
      1995, respectively. The migration distances for men and women in the same years
      were 477, 725, and 986 km and 383, 609, and 866 km, respectively. The radius of
      the Belgorod population in terms of Malecot's isolation by distance model
      increased in the period studied (55, 81, and 95 km in 1960, 1985, and 1995,
      respectively). The parameter b in that period decreased (0.00110, 0.00074, and
      0.00062, respectively), which indicates a decrease in the inbred component. The
      increase in marital distance (590, 796, and 891 km in 1960, 1985, and 1995,
      respectively) indicates a steady increase in the outbred component of the
      population.

PMID- 15977823
TI  - [Developing and testing a method of in silico identification and characterization
      of meiotic DNA].
AB  - A method of in silico search for specific repetitive DNA sequences related to the
      synaptonemal complex (meiDNA) in mammalian genomes was developed. A study of the
      distribution of these repeats over chromosomes revealed their scarcity on the Y
      chromosome and a decrease in recombination frequency in regions enriched in
      meiDNA. The results are discussed in context of the model of the looplike meiotic
      chromosome organization during the formation of the synaptonemal complex.

PMID- 15977824
TI  - Genetic regulation on the black phenotype mutants of moth and pupa of Helicoverpa
      armigera (Lepidoptera: Noctuidae).
AB  - Genetic regulation on body color of a mutant strain, JBM of Helicoverpa armigera
      with black body color of pupae and adults, was investigated. Reciprocal crosses
      between JBM and JBW (a wild strain with yellow brown body color of pupae and
      adults) were used to determine the inheritance characteristics of body color.
      Analysis of the ratio of phenotype segregation from the F1 generation, F2
      generation, F3 generation, BC1 (F1 x JBM) generation and F1 generation of BC1
      indicated that the black body color was controlled by one recessive gene.

PMID- 15977825
TI  - [Some achievements of the Russian Program "molecular and cell biology" in 2003].

PMID- 15977826
TI  - [The analysis of monomer sequences in protein and tRNA and the manifestation of
      the compensation of pathogenic deviations in their evolution].
AB  - The sequence analysis of proteins and mitochondrial tRNA indicated that
      substitutions inducing the pathogenesis in humans often occur in normal
      individuals of other species having no signs of pathology. The analysis of the
      structural stability of the protein and tRNA molecules showed that the harmful
      effect of pathogenic substitutions is often neutralized by other compensatory
      substitutions, which restore the required normal stability of the structure. A
      further study of this phenomenon will probably lead to new methods of treatment
      of genetic pathology, which would be based not on the correction of one
      substitution but on the correction of the stability of the molecule as an entire
      functional unit.

PMID- 15977827
TI  - [The convergent evolution of the secondary structure of mitochondrial cysteine
      tRNA in the nine-banded armadillo Dasypus novemcinctus].
AB  - The case of the convergent loss of the D-hairpin in mitochondrial cysteine tRNA
      of the nine-banded armadillo Dasypus novemcinctus is described. This evolutionary
      event sheds light on the molecular structure-function relationship and on the
      effect of this relationship on the processes of evolution of biopolymers and
      macromolecules.

PMID- 15977828
TI  - [The structure-function organization of neurokinin A and neurokinin B molecules.
      II. Theoretical conformational analysis of neurokinin B].
AB  - The spatial structure of a neurokinin B molecule was investigated by the method
      of theoretical conformational analysis. The conformational analysis of this
      molecule indicated that the possible structure of neurokinin B under polar
      conditions may be described by five families of low-energy conformations
      possessing a conformationally relatively rigid C-terminal heptapeptide and
      variable N-terminal fragments.

PMID- 15977829
TI  - [A peptide inhibitor of the binding site of oncoproteins of the p21ras family].
AB  - The method of theoretical conformational analysis was used to study the inverse
      structural problem to determine the amino acid sequence of the peptide molecule
      capable of inhibiting the site of binding of p21 to cell receptors. At the first
      stage of the computational experiment, the spatial structure and the
      conformational possibilities of the binding sites of protein p21 and its cellular
      receptors were determined. Then the three-dimensional structures of several
      peptides containing the Arg-Ala-Ala-Glu-Asp site were studied. By varying the
      number of alanine residues in the adjacent regions of the molecule, the sequence
      H-Asp1-Ala2-Ala3-Ala4-Arg5-Ala6-Ala7-Glu8-Asp9-Ala10-Ala11--Lys12-QH was chosen,
      which most adequately simulates the conformational properties of the address
      fragments of oncoprotein receptors. The peptide-molecule having this primary
      structure is capable of forming a complex with p21, i.e., blocking the binding
      site of the oncoprotein by preventing the signal transduction from the
      oncoprotein to the cell, thereby breaking the cycle of the carcinogenic process.

PMID- 15977830
TI  - [The modeling of interactions of the CYP2E1 isoform of human cytochrome P450 with
      substrates].
AB  - The interactions between the substrates of the 2E1 isoform of the human
      cytochrome P450 and receptor were simulated. It was found that the CP4 isoform of
      the cytochrome of the bacterial cell is highly homologous to the 2E1 isoform of
      the human cytochrome P450. The orientation of the substrates of the 2E1 isoform
      in the CP4 isoform of the bacterial cell cytochrome was performed. A cavity in
      the receptor was found that is responsible for the binding of the substrate.
      Amino acid residues Phe87, Pro89, Val119, Thr185, Leu244, Leu245, Leu246, Val247,
      Gly248, Gly249, Thr252, Val295, Asp297, Cys357, Ile395, and Val396, the heme, and
      water molecules are involved in the formation of the cavity. The mode of the
      interactions of the substrate molecule with cytochrome was analyzed. Active sites
      of the receptor, and a part of the substrate molecule responsible for the binding
      to cytochrome were found. Equations for the dependence of the Michaelis constant
      on the structural parameters of complexes of substrates with cytochrome were
      derived.

PMID- 15977831
TI  - [The electrostatic contribution to interactions of some enzymes with
      polyelectrolytes].
AB  - To explain the inhibitory action of polyelectrolytes on enzymes and, in
      particular, to define potentially reactive zones for the binding of
      polyelectrolyte, the electric potential of enzymes lactate dehydrogenase and
      glutamate dehydrogenase was calculated using the solution of the Poisson
      Boltzmann equation by a numerical method with the use of the Gauss-Seidel
      relaxation method at three pH values: 6.5, 7.0, and 8.0 and three values of ionic
      strength: 50, 100, and 150 mm. On the basis of these calculations and their
      visualization, representative sites for favorable binding of polyanions were
      determined as extended areas on the surface of proteins with the positive
      potential in the neutral pH region. It was shown that there is a correlation
      between the area of positive potential and the efficiency of enzyme inactivation
      for a number of pH values and concentrations of salt for two enzymes. The
      calculations performed allowed one to explain the inhibitory action of
      polyelectrolytes on the specified enzymes to understand the difference between
      the values of polyelectrolyte inactivation constants for the two enzymes and
      estimate the minimal areas of the positive potential on the protein surface that
      provide their effective inhibition.

PMID- 15977832
TI  - [The mechanism of accumulation of the large electric dipole moment of DNA
      molecule. PM3 quantum-chemical analysis].
AB  - On the basis of the idea of the intrinsic polymorphism of Watson-Crick base
      pairing in DNA structure, the process of accumulation of the large electric
      dipole moment in model spiral stacks of canonical non-planar AT and GC pairs was
      analyzed using the quantum-chemistry methods. The dependence of the value and
      orientation of electrical dipole moment of a double helix on spiral length,
      geometry of base H-pairing, and the bending of the major axis of the helix were
      considered.

PMID- 15977833
TI  - [Some principles in the organization of sigma70-specific promoters on the E. coli
      genome on the basis of electrostatic patterns of promoter DNA].
AB  - The distribution of electrostatic potential of the complete sequence of the E.
      coli genome was calculated. It was found that DNA is not a uniformly charged
      molecule. There are some local inhomogeneities in its electrostatic profile,
      which correlate with the position of promoters in the genome. Electrostatic
      patterns of promoter DNAs can be specified due to the presence of some
      distinctive motifs, which may be involved as promoter signal elements in RNA
      polymerase-promoter recognition.

PMID- 15977834
TI  - [One- and two-soliton solutions for DNA].
AB  - One- and two-soliton solutions of the nonlinear differential equation imitating
      rotational oscillations of DNA bases were found. It was shown that the equation
      is analogous to the simple sine-Gordon equation, which is solved by the inverse
      scattering method using the L-A pair. One- and two-soliton solutions found by the
      method were presented in terms of DNA parameters. The profiles of nonlinear one
      soliton waves were calculated for two cases: for a homogeneous double
      polynucleotide chain consisting of A-T base pairs and for a homogeneous double
      polynucleotide chain consisting of G-C base pairs.

PMID- 15977835
TI  - [The genotoxic action of uranyl ions on DNA in vitro caused by the generation of
      reactive oxygen species].
AB  - 8-Oxoguanine (8-OG) is an important biomarker of oxidative DNA damage induced by
      reactive oxygen species (ROS). By using ELISA with monoclonal antibodies against
      8-OG, the formation of 8-OG in DNA by the action of uranyl ions, gamma
      irradiation, and heating at 37 degrees C and their combined action was
      investigated in view of environmental pollution by uranium oxides as a result of
      the use of armor piercing shells with depleted uranium. The content of 8-OG in
      DNA induced by the action of gamma-irradiation, 5 microM uranyl ions and heating
      changes with time in a complicated manner. These results suggest that, by the
      action of uranyl ions, an additional generation of ROS occurs, which leads both
      to the formation of 8-OG in DNA and its further oxidation. Uranyl ions at a
      conceptration of 5 microM increase the thermal deamination of cytosine in DNA
      several times but do not influence DNA thermal depurination. It is shown that
      uranyl ions essentially increase the production of hydrogen peroxide and hydroxyl
      radicals by the action of heat on water. The results indicate a high chemical
      genotoxicity of uranyl ions and their enhancing effect on DNA base damage by the
      action of heat and gamma-irradiation.

PMID- 15977836
TI  - [An experimental study of potentiated aqueous solutions].
AB  - A systematic study was undertaken of luminescent aqueous solutions of homeopathic
      preparation of sodium chloride at a dilution from D1 to D30, produced by "Weleda"
      company (Moscow) was carried out. It was shown that intensity of luminescence
      versus the degree of dilution is a non-monotonous function with several maxima,
      the main maximum corresponds to 13-14 decimal dilution. The dynamics of spectra
      was registered for several weeks. A systematic study of water samples (D1-D30)
      exposed to a similar procedure of potentization but without salt addition was
      also performed. The difference in the luminescence spectra of water of different
      stages of potentization was shown. The motility of infusoria Spirostoma ambiquum
      in solutions being examined was studied. A significant negative correlation
      between the infusoria motility and luminescence intensity was registered.

PMID- 15977837
TI  - [Conformational and intermolecular interactions of proteins in amyloidosis].
AB  - A conception on amyloidosis as a key factor of neuronal death in
      neurodegenerative diseases is stated. Experimental evidence is presented that
      amyloidosis is caused by alterations in the activity of a number of enzymes as
      well as conformational changes in pathogenic proteins. Arguments for amyloidosis
      as the universal biological mechanism of specific elimination of neurons showing
      changed metabolic and physiological status of cell differentiation are adduced.
      The final pattern of cell death seems to differ cardinally from that in both
      apoptosis and necrosis.

PMID- 15977838
TI  - [A protocol of automatic alignment of genome sequences using the program OWEN].
AB  - A protocol of automatic hierarchical alignment of long DNA sequences using the
      program OWEN is described. The protocol is based on the command line regime of
      the program OWEN. The protocol makes it possible to align a large number of pairs
      of moderately similar sequences automatically. We used this protocol to align
      8623 orthologous pairs of intergenic regions in human and murine genomes.

PMID- 15977839
TI  - [The dynamics of the domains of the IP3-binding site of the inositol-1,4,5
      triphosphate-sensitive calcium channel, induced by inositol-1,4,5-triphosphate
      and calcium].
AB  - The dynamics of the inositol-1,4,5-triphosphate-sensitive calcium channel after
      binding of inositol-1,4,5-triphosphate and Ca2+ was analyzed by the Monte Carlo
      minimization technique. It was shown that the binding of Ca2+ with the unliganded
      receptor (channel) leads to a turning of the beta-sheet domain relative to the
      alpha-helical domain with the formation of the receptor conformation that is open
      for the entry of ions into the cytoplasmic channel vestibule, sterically closed
      for their passage through the vestibule in the part adjacent to the alpha-helical
      domains, and unfavourable for subsequent binding of inositol-1,4,5-triphosphate
      with the receptor. When both co-agonists bind to the receptor, the structure
      rearrangements induced eliminate both these steric obstacles for the passage of
      ions through the IP3-binding domain: one at the entrance of the channel
      cytoplasmic vestibule and the other that is placed deeper in the vestibule near
      the alpha-domains. The role of the dynamics of the receptor binding core in the
      IP3-sensitive channel gating is discussed.

PMID- 15977840
TI  - [The role of different conformational states of receptors in the formation of
      synaptic plasticity].
AB  - A mathematical model was proposed that explains the formation of successive
      temporal stages of synaptic plasticity in terms of the transition of post
      synaptic ionotropic receptors to different conformational states.

PMID- 15977841
TI  - [Modelling of pattern formation and oscillations in pH and transmembrane
      potential near the cell membrane of Chara corallina].
AB  - A mathematical model of potencial-dependent proton transfer across the membrane
      of Chara corallina cells is considered. To construct the model, partial
      differential equations describing the system dynamics in time and in space were
      used. The variables of the model are the proton concentration and membrane
      potential. The model describes the experimentally observed inhomogeneous
      distribution of transmembrane potential and pH along the membrane and
      oscillations of the potential and pH in time. A mechanism of the distribution of
      pH and membrane potential along the Chara corallina cell is suggested.

PMID- 15977842
TI  - [Changes in the permeability of amphibian embryo envelope for fluorochromes under
      the action of ultrasound].
AB  - It was determined whether high-frequency ultra sound can change the permeability
      of gray toad Bufo bufo and grass frog Rana temporaria under the action of high
      frequency ultrasound. The changes in the permeability of embryonic envelope were
      assessed by using slowly penetrating fluorochromes ANS, FDA, and fluorescein. It
      was found that the ultrasound of 0.88 MHz and 0.4 - 0.7 W/cm2 intensity increased
      the permeability of amphibian embryonic envelope for ANS and FDA, whereas the
      ultrasound of 2.64 MHz and the same intensity increased that for fluorescein with
      the retention of low permeability for FDA. Embryos continued the normal
      development after treatment with ultrasound under these conditions.

PMID- 15977843
TI  - [Modeling of the evolution of a water-remedying biofilm with consideration for
      its erosion].
AB  - A model is proposed that describes the growth and destruction of a biofilm due to
      the consumption of contaminants dissolved in the water being purified. The
      mathematical solution involves equations describing the balance of biomass, the
      delivery and uptake of substrate, and the dynamics of biofilm thickness. The
      effect of erosion on the characteristics of the steady-state regime was shown.
      The concentrations of the substrate and biomass, the flow of the substrate into
      the film, and changes in biofilm thickness were calculated.

PMID- 15977844
TI  - [Mathematical models of nitric oxide transport in a blood vessel].
AB  - The appearance of this review concerning the nitric oxide transport in a blood
      vessel wall is connected with the authors' interest in vessel tone regulation.
      The introductory part contains basic equations for resistive vessels, an outline
      of processes occurring in smooth muscle and endothelial cells, and the simulation
      of these processes. As a rule, the description of nitric oxide diffusion and
      reactions in blood vessels is given in the order of increasing complication of
      the models. Primary attention is given to the consideration of systems with
      endothelial production of nitric oxide, but articles considering other sources of
      nitric oxide are also reviewed. The theoretical methods of evaluating the
      parameters that are important for modeling but hardly measurable are described.

PMID- 15977845
TI  - [The registration of nitric oxide production in mammals using a water-soluble
      complex of N-methyl-D,L-glucamine dithiocarbamate with Fe3+].
AB  - The level of nitric oxide production in the intact rabbit organism was studied
      using the water-soluble complex of Fe3+ with MGD as a selective spin trap for
      nitric oxide. The Fe(3+)-MGD3 complex was injected intravenously. It was shown by
      the EPR method that this injection resulted in the formation of paramagnetic
      complexes in the urine, as Cu(2+)-MGD2, and nitric oxide spin adducts: nitric
      oxide-Fe(2+)-MGD2 and nitric oxide-Fe(3+)-MGD2. The level of nitric oxide
      production was estimated by the ratio of the total amount of these adducts to the
      nitric oxide-Fe(2+)-MGD2 level, formed after the addition of excessive S
      nitrosoglutathione. This value for intact animals was 1.33 +/- 0.13%.

PMID- 15977846
TI  - [Mathematical modeling of oxygen diffusion and consumption in malignant tumor].
AB  - A mathematical model of oxygen diffusion and consumption in a malignant spherical
      tumor was developed. The model takes into account the dependence of the rate of
      oxygen consumption by cells on oxygen concentration. The expressions for the
      description of the dependence of oxygen concentration on the coordinate in the
      tumor are presented. Some model parameters were estimated from known experimental
      data. The hypoxic cells fraction (index related to tumour radioresistance) at
      critical and limiting tumor sizes were calculated.

PMID- 15977847
TI  - [A study of biological fluids by ultrasound coagulography].
AB  - A new methodology: the method and technical means for studying the coagulation of
      blood and the acoustic properties of other biological fluids (ultrasound
      coagulography) was developed. The complex of devices is based on the principle of
      measuring the rate of ultrasound in a medium studied by means of the impulse
      method. Arguments for the applicability of the method for studying the process of
      blood coagulation are adduced, special acoustic chambers were designed, and
      algorithms and computer programs for immediate processing of the data were
      developed. The field of application is biology and medicine: studies of the
      acoustic properties of biological fluids (e.g., blood coagulation), rheological
      properties, and viscosity of the object for the diagnosis of some diseases. The
      results of clinical assays of blood coagulation in healthy persons are presented.

PMID- 15977848
TI  - [The investigation of the influence of cryopreservation and inbreeding on the
      variability of morphological characteristics of the evening-primrose biennial
      (Oenothera biennis L.)].
AB  - The effect of deep freezing of seeds at -196 degrees C (-320.8 degrees
      Fahrenheit) and inbreeding on the morphological characteristics of the evening
      primrose biennal (Oenothera biennis L.), such as the size of plant parts and the
      amount of fruits, cauline nodes, and generative and vegetative shoots was
      investigated. The variation coefficients for these characteristics after
      treatment with low temperatures and inbreeding were calculated. It was shown that
      the characteristics of plant size show a low and a middle level of variability in
      the control group. The variation curves for these characteristics are similar to
      normal distribution curves. After stresses they slightly change or remain
      invariant. Large adventive shoots show a high level of variability. The
      distribution of the results in this case significantly differs from the normal.
      The branching of plants changes after both stress factors: the amount of all
      kinds of shoots decreases by half or even more.

PMID- 15977849
TI  - [Evolutionary stability in the dynamics of populations having short reproduction
      periods].
AB  - A special class of models of competition (D-systems) were constructed in which
      the coefficients of population growth are periodic delta-functions. Effective
      methods for the analysis of the global dynamics of D-systems were proposed. In
      the framework of this model system, the problem of the existence of
      evolutionarily stable parameters, the periods of reproduction of populations in a
      variable medium, was studied. Using analytical methods and the data of computer
      assisted experiments, open sets of evolutionarily stable parameters were found.

PMID- 15977850
TI  - Lessons learned.

PMID- 15977851
TI  - Treating obesity: new advice from the American College of Physicians.

PMID- 15977852
TI  - How PAs live and work.

PMID- 15977853
TI  - Evaluation and management of hypercalcemia.

PMID- 15977854
TI  - Atrial fibrillation: new theories, emerging treatments.

PMID- 15977855
TI  - Hypothermia--potentially deadly year round.

PMID- 15977856
TI  - Painless lesions and an odd biopsy result.

PMID- 15977858
TI  - Patient information. From your physician assistant. How to prevent a stroke.

PMID- 15977857
TI  - Using aspirin to prevent stroke.

PMID- 15977859
TI  - Fast track in the field: another option to ease ED overcrowding.

PMID- 15977860
TI  - Diagnostic challenges from your case files. Left slipped capital femoral
      epiphysis (SCFE).

PMID- 15977861
TI  - Ultrasonic evaluation in retinopathy of prematurity.

PMID- 15977862
TI  - Optical coherence tomography in children with retinoblastoma.

PMID- 15977863
TI  - Refractive errors in infants.

PMID- 15977864
TI  - What's your diagnosis? Buphthalmos with neurofibromatosis (NF-1).

PMID- 15977865
TI  - Benefits of unilateral anterior transposition of the inferior oblique muscle.

PMID- 15977866
TI  - Three-muscle surgery for infantile esotropia in children younger than age 2
      years.
AB  - PURPOSE: To review the long-term outcome of infants undergoing three-muscle
      surgery for infantile esotropia. PATIENTS AND METHODS: Surgical records of 10
      patients with esotropia > or = 55 prism diopters (PD) who underwent three-muscle
      surgery for large-angle infantile esotropia were reviewed. Outcome measures
      included over- or undercorrection, need for additional surgery, and amount of
      deviation at last follow-up. RESULTS: Mean age at initial surgery was 13 months.
      Mean preoperative deviation was 62.5 PD of esotropia. A single surgery was
      associated with satisfactory horizontal alignment in only three (30%) patients at
      last follow-up (mean, 37.1 months; range, 8-70 months). Esotropia was
      undercorrected in one (10%) and overcorrected in six (60%) patients, all of whom
      required additional surgery. One patient with satisfactory horizontal alignment
      required an additional procedure to correct a right hypertropia causing a left
      face turn. CONCLUSIONS: In contrast to older children and adults, three-muscle
      surgery may be inappropriate for infants with large-angle esotropia due to a
      large overcorrection rate. This controversy may benefit from a prospective study.

PMID- 15977867
TI  - Ocular growth pattern in cryotherapy- and laser-treated infants with prethreshold
      retinopathy of prematurity.
AB  - PURPOSE: To study the ocular growth pattern in cryotherapy- and laser-treated
      prethreshold retinopathy of prematurity (ROP) and its effect on scleral rigidity.
      METHODS: In a prospective study, axial length, anterior chamber depth, and
      scleral rigidity were assessed in 12 eyes with no ROP, 12 eyes with spontaneously
      regressed ROP, 12 eyes with cryotherapy-treated prethreshold ROP, and 14 eyes
      with diode laser-treated prethreshold ROP at 36 weeks, 40 weeks, and 52 weeks
      postconceptional age. RESULTS: Cryotherapy- and laser-treated ROP eyes at
      prethreshold stage exhibited shorter axial lengths and shallower anterior chamber
      depth compared to eyes with no ROP or spontaneously regressed ROP. Scleral
      rigidity was not altered in ROP eyes including those that underwent cryotherapy
      or laser treatment. CONCLUSIONS: Growth of eyes with ROP is arrested including
      those treated with cryotherapy or laser at prethreshold stage. Cryotherapy or
      laser treatment has no weakening effect on the scleral coat.

PMID- 15977868
TI  - Introduction of the Low Vision Evaluator (LoVE) for children.
AB  - PURPOSE: To determine whether the Low Vision Evaluator (LoVE) can grade the
      visual acuity of young children with light perception and hand movement acuity
      into finer acuity steps and at what age reliable measurements can be obtained.
      METHODS: Two hundred twenty children were tested with the LoVE. Each eye was
      tested separately, and each stimulus magnitude (intensity x duration) was
      presented three times. Three catch trials per eye also were presented. RESULTS:
      Scores ranged from -8 to -1 on variable-duration tests and from 22.5 to 37.5 dB
      on fixed-duration tests for four children with hand movement vision. Scores
      ranged from -12 to 0 on variable-duration tests and from 12.5 to 40 dB on fixed
      duration tests for five children with light perception vision. Reliable
      measurements were obtained at different times on different days. Mean scores for
      children with counting finger vision or better were significantly better than
      scores for eyes with light perception and hand movement (P < .001 and P < .01,
      respectively). Reliability was less for children younger than age 4 years.
      CONCLUSIONS: The LoVE is capable of grading the visual function of children with
      light perception and hand movement vision into finer steps. Reliable measurements
      can be obtained for children age 4 years and older.

PMID- 15977869
TI  - Unilateral anterior transposition and resection of the inferior oblique muscle
      for the treatment of hypertropia.
AB  - BACKGROUND: Anterior transposition of the inferior oblique muscle generally is
      restricted to bilateral cases because of reports of postoperative ipsilateral
      hypotropia or significant limitation of elevation when performed unilaterally. We
      performed unilateral anterior transposition of the inferior oblique muscle in
      patients with vertical and horizontal strabismus who were at risk of anterior
      segment ischemia. PATIENTS AND METHODS: Six patients underwent unilateral
      anterior transposition of the inferior oblique muscle in combination with a
      resection of the inferior oblique muscle. Two patients had lost an inferior
      rectus muscle in a previous procedure, and four patients had coexistent
      horizontal and vertical strabismus of various etiologies as well as poor
      unilateral vision. RESULTS: All six patients achieved vertical alignment within
      10 prism diopters. CONCLUSIONS: Unilateral anterior transposition of the inferior
      oblique muscle appears to be a useful procedure in selected patients with
      vertical strabismus.

PMID- 15977870
TI  - Comparison of mydriatic regimens used in screening for retinopathy of prematurity
      in preterm infants with dark irides.
AB  - PURPOSE: To determine the mydriatic regimen that provides optimal dilation of the
      pupil with minimal systemic side effects for screening of retinopathy of
      prematurity. METHODS: This cross-sectional, randomized, double-masked clinical
      trial compared cyclopentolate 1% + phenylephrine 2.5%, tropicamide 1% +
      phenylephrine 2.5%, and a prepared combination of cyclopentolate 0.2% with
      phenylephrine 1% for pupillary dilation in preterm infants with dark irides.
      Thirteen infants were randomized to each regimen. Outcomes measured were
      pupillary dilation, heart rate, blood pressure, abdominal girth, and intolerance
      to feeds. RESULTS: All three mydriatic regimens provided adequate pupillary
      dilation at 45 minutes, with dilation sustained at 60 minutes. There was a
      significant increase in mean blood pressure in the cyclopentolate 1% +
      phenylephrine 2.5% and the tropicamide 1% + phenylephrine 2.5% groups. Although
      there was no significant change of abdominal girth in any of the three groups, a
      total of eight patients developed intolerance to feeds; four (50%) of these
      infants were from the cyclopentolate 1% + phenylephrine 2.5% group. CONCLUSION:
      The prepared combination of cyclopentolate 0.2% + phenylephrine 1% appears to be
      the mydriatic of choice for preterm infants with dark irides as it provided
      adequate pupillary dilation with the least systemic side effects.

PMID- 15977871
TI  - Isolated anisocoria from an endodermal cyst of the third cranial nerve mimicking
      an Adie's tonic pupil.
AB  - We present only the second reported case in the literature of a neuroenteric cyst
      involving the third cranial nerve. Our case is highlighted by the initial
      presentation of an isolated anisocoria, initially believed to represent an Adie's
      tonic pupil as interpreted by pharmacologic testing. False-positive results may
      occur with the dilute pilocarpine test.

PMID- 15977872
TI  - Surgically induced necrotizing scleritis occurring 48 years after strabismus
      surgery.
AB  - We present a 52-year-old woman who was diagnosed with surgically induced
      necrotizing scleritis 48 years after strabismus surgery. This case demonstrates
      the importance of a high index of suspicion for this sight-threatening condition,
      even many years after strabismus surgery.

PMID- 15977873
TI  - Chorioretinitis as a complication of pauciarticular juvenile rheumatoid
      arthritis.
AB  - A girl with pauciarticular juvenile rheumatoid arthritis developed bilateral
      uveitis complicated by cataract and glaucoma. Sequential fundus photography
      documented development of extensive choroidal scarring and retinal pigment
      epithelial atrophy in the left macula. Vision was not impaired. This case
      suggests uveitis in juvenile rheumatoid arthritis can be associated with
      chorioretinitis.

PMID- 15977874
TI  - Orbital pseudotumor in a child with juvenile rheumatoid arthritis.
AB  - We report a child with persistent fevers, arthritis, and parvoviral infection who
      subsequently developed unilateral orbital pseudotumor, lytic bone lesions,
      bilateral anterior uveitis, band keratopathy, and migratory polyarthritis. Our
      working diagnosis was systemic-onset juvenile rheumatoid arthritis, although
      pseudotumor of the orbit and lytic bone lesions are not found in this disease.

PMID- 15977875
TI  - Corneal keloid mimicking a recurrent limbal dermoid.
AB  - We report a 12-year-old boy who presented with the clinical appearance of a
      limbal dermoid recurrence. Histologic study of the lesion revealed it to be a
      corneal keloid. In the event of a recurrent mass following dermoid excision,
      keloid should be considered in the differential diagnosis.

PMID- 15977877
TI  - Corneal transplantation as a refractive surgical procedure.

PMID- 15977876
TI  - Juvenile xanthogranuloma.

PMID- 15977878
TI  - Implantation of Artisan toric phakic intraocular lenses for the correction of
      astigmatism and spherical errors in patients with keratoconus.
AB  - PURPOSE: To evaluate the correction of astigmatism and spherical ametropia in
      patients with keratoconus through implantation of an Artisan toric phakic
      intraocular lens (PIOL) (Ophtec, Groningen, The Netherlands). METHODS: Artisan
      toric PIOLs were implanted uneventfully in both eyes of three patients with
      keratoconus with clear central corneas and contact lens intolerance. RESULTS:
      Best spectacle-corrected subjective visual acuity after lens implantation was
      unchanged in one eye and improved in five eyes. Spherical equivalent refraction
      was significantly reduced in all eyes (P=.03). The safety index was 1.49.
      CONCLUSIONS: The implantation of an Artisan toric PIOL may be an alternative for
      treating astigmatism and myopia in contact lens intolerant patients with
      keratoconus with clear central corneas. Especially in patients with associated
      myopia, this procedure is worth considering before planning a penetrating
      keratoplasty.

PMID- 15977879
TI  - Optical quality and depth-of-field of eyes implanted with spherical and aspheric
      intraocular lenses.
AB  - PURPOSE: To compare experimental optical performance in eyes implanted with
      spherical and aspheric intraocular lenses (IOLs). METHODS: Corneal, total, and
      internal aberrations were measured in 19 eyes implanted with spherical (n=9) and
      aspheric (n=10) IOLs. Corneal aberrations were estimated by virtual ray tracing
      on corneal elevation maps, and total aberrations were measured using a second
      generation laser ray tracing system. Corneal and total wave aberrations were fit
      to a Zernike polynomial expansion. Internal aberrations were measured by
      subtracting corneal from total wave aberrations. Optical performance was
      evaluated in terms of root-mean-square (RMS) wavefront error and Strehl ratio
      (estimated from the modulation transfer function). Depth-of-field was obtained
      from through-focus Strehl estimates from each individual eye. RESULTS: Corneal
      aberrations increased after IOL implantation, particularly astigmatism and
      trefoil terms. Third and higher order RMS (and the corresponding Strehl ratio)
      were significantly better in eyes with aspheric IOLs than with spherical IOLs;
      however, this tendency was reversed when astigmatism was included. Spherical
      aberration was not significantly different in eyes with aspheric IOLs, whereas it
      was significantly positive in eyes with spherical IOLs. Third order aberrations
      were not significantly different across groups. Depth-of-field was significantly
      larger in eyes with spherical IOLs. Spherical IOLs showed better absolute optical
      quality in the presence of negative defocus >1.00 D. CONCLUSIONS: Our study shows
      a good degree of compensation of the corneal spherical aberration in eyes
      implanted with aspheric IOLs, as opposed to eyes implanted with spherical IOLs.
      Other sources of optical degradation, both with aspheric and spherical IOLs, are
      non-symmetric preoperative corneal aberrations, incision-induced aberrations, and
      third order internal aberrations. Although best corrected optical quality is
      significantly better with aspheric IOLs, tolerance to defocus tended to be lower.

PMID- 15977880
TI  - Treating keratoconus with intacs corneal ring segments.
AB  - PURPOSE: To assess the safety and efficacy of Intacs inserts for the treatment of
      mild to moderate keratoconus. METHODS: In a nonrandomized prospective clinical
      trial, 50 eyes of 37 patients with mild to moderate keratoconus were implanted
      with asymmetrical pairs of Intacs segments. Patients were interviewed and
      observed preoperatively and 24 hours, 1 week, 1, 3, 6, and 12 months
      postoperatively. Main outcome measures were uncorrected visual acuity (UCVA),
      best spectacle-corrected visual acuity (BSCVA), refraction, satisfaction with
      vision and trouble with vision, Visual Function-7 score, and surgically induced
      change in corneal astigmatism. RESULTS: Of the 50 operations performed, 92% were
      successful. Mean follow-up was 6.3 +/- 3.2 months. In 4 (8%) eyes, both Intacs
      segments were removed. In addition, 7 refractive adjustments in 7 eyes were
      performed successfully to improve visual and surgical outcome. Both BSCVA and
      UCVA improved throughout follow-up. Visual functioning index improved from 61.6
      +/- 21.1 to 80.8 +/- 22.5, and the percentage of satisfaction with vision
      improved from 24.3% to 87.5% at 12 months. Vector analysis of astigmatism
      correction showed that the mean change in corneal astigmatism was 2.9 +/- 2.9 D
      at 6 months postoperatively. By selecting patients in whom astigmatism correction
      was best (index of success >0.5), an analysis was performed to determine
      individual factors important in successful surgery. Preoperatively these 11 (22%)
      eyes did not differ significantly from the remaining eyes and the only
      significant value was low K readings in the flat axis. CONCLUSIONS: Asymmetric
      Intacs placement improves BSCVA and UCVA and reduces astigmatism in patients with
      mild to moderate keratoconus. The procedure of Intacs placement is safe and
      effective. The change in astigmatism correction is unpredictable.

PMID- 15977881
TI  - Intracorneal hydrogel lenses and corneal aberrations.
AB  - PURPOSE: To investigate the optical performance of the cornea based on corneal
      aberrometry following intracorneal hydrogel lens implantation. METHODS: A
      retrospective, nonconsecutive, observational study of the anterior corneal
      surface aberration profile of four hyperopic eyes previously implanted with an
      intracorneal hydrogel lens were studied by videokeratographic elevation maps
      before and 6 months after surgery. RESULTS: Intracorneal hydrogel lenses reduced
      the optical performance in all four eyes by increasing the spherical aberrations
      by a mean factor of 1.87 and 1.95, coma aberrations by a mean factor of 2.98 and
      3.01, and total higher order aberrations by a mean factor of 2.6 and 2.17 at 3.0
      mm and 6.5-mm pupils, respectively (P<.005). CONCLUSIONS: Intracorneal hydrogel
      lenses decreased the optical performance of the cornea by significantly
      increasing spherical, coma, and total higher order aberrations.

PMID- 15977882
TI  - Factors predictive of LASIK flap thickness with the Hansatome zero compression
      microkeratome.
AB  - PURPOSE: To determine the explanatory power of preoperative variables and comeal
      flap thickness in laser in situ keratomileusis (LASIK) using the Hansatome zero
      compression microkeratome (Bausch & Lomb, Rochester, NY). METHODS: A prospective,
      nonrandomized, comparative interventional case study was performed on 250 eyes of
      129 consecutive patients who underwent LASIK surgery using the Hansatome zero
      compression microkeratome. A 160-microm or 180-microm microkeratome head and an
      8.5- or 9.5-mm suction ring were used in the procedures. Preoperative
      measurements included refraction, spherical equivalent, keratometry, intraocular
      pressure, corneal white-to-white, anterior chamber depth, and corneal
      eccentricity. Corneal thickness was measured intraoperatively using ultrasonic
      pachymetry before and after flap creation, and the difference was taken as flap
      thickness. Flap diameter was measured with a corneal gauge. Data were analyzed
      using simple, multiple, stepwise linear and non-linear regression analyses and
      two-tailed t tests. RESULTS: The mean flap thickness was 124 +/- 17 microm with
      the nominal 160-microm head and 142 +/- 20 microm with the nominal 180-microm
      head. One third (33%) of the total variation in flap thickness could be accounted
      for by three preoperative variables: average corneal thickness, spherical
      equivalent refraction, and choice of 160- or 180-microm microkeratome head. A
      simple correlation of 0.114 was noted between corneal eccentricity and flap
      thickness, but this variable did not add significant explanatory power on
      multiple regression analysis. Linear regression analysis allowed determination of
      a flap thickness nomogram with a standard error of the estimate of 16.9 microm
      and a 95% confidence interval of +/- 33.1. CONCLUSIONS: Comeal thickness is the
      most systematic predictor of corneal flap thickness using the Hansatome
      microkeratome. Because three preoperative variables account for only 33% of the
      range in flap thickness, future studies should focus on variations in blade
      extension and corneal biomechanical factors, which may also play an important
      role in determining flap thickness.

PMID- 15977883
TI  - Surface roughness after excimer laser ablation using a PMMA model: profilometry
      and effects on vision.
AB  - PURPOSE: To show that the limited quality of surfaces produced by one model of
      excimer laser systems can degrade visual performance with a
      polymethylmethacrylate (PMMA) model. METHODS: A range of lenses of different
      powers was ablated in PMMA sheets using five DOS-based Nidek EC-5000 laser
      systems (Nidek Technologies, Gamagori, Japan) from different clinics. Surface
      quality was objectively assessed using profilometry. Contrast sensitivity and
      visual acuity were measured through the lenses when their powers were neutralized
      with suitable spectacle trial lenses. RESULTS: Average surface roughness was
      found to increase with lens power, roughness values being higher for negative
      lenses than for positive lenses. Losses in visual contrast sensitivity and acuity
      measured in two subjects were found to follow a similar pattern. Findings are
      similar to those previously published with other excimer laser systems.
      CONCLUSIONS: Levels of surface roughness produced by some laser systems may be
      sufficient to degrade visual performance under some circumstances.

PMID- 15977884
TI  - Effect of refractive and topographic astigmatic axis on LASIK correction of
      myopic astigmatism.
AB  - PURPOSE: To evaluate whether agreement or disagreement between the axis of
      astigmatism as determined by refraction and corneal topography has any influence
      on the outcome of laser in situ keratomileusis (LASIK) correction of astigmatism.
      METHODS: Charts of 122 consecutive eyes of 75 patients (46 women and 29 men) who
      underwent uncomplicated, primary LASIK for myopic astigmatism were reviewed. The
      series was divided into two groups--group 1, "agreement" (77 eyes) with a
      difference between refractive and topographic axis of astigmatism < or = 15
      degrees, and group 2, "disagreement" (45 eyes) with a difference > 15 degrees.
      RESULTS: The mean difference in axis of astigmatism was 10 +/- 17.20 degrees
      (range: 0 degrees to 86 degrees), and 63.11% of eyes were within a 15 degrees
      difference. A significant negative correlation was found between the percentage
      of corrected astigmatism and the degree of disagreement. The percentage of
      corrected astigmatism differed significantly between the two groups (P=.002) with
      better results in group 1 (agreement). CONCLUSIONS: Disagreement between
      refractive and topographic astigmatic axis is common. Approximately one third of
      eyes with astigmatism have > 15 degrees disagreement. Disagreement between
      refractive and topographic determination of the astigmatic axis can be considered
      a prognostic factor for LASIK correction of myopic astigmatism.

PMID- 15977885
TI  - Rates of epithelial ingrowth after LASIK for different excimer laser systems.
AB  - PURPOSE: To investigate the incidence of epithelial ingrowth after laser in situ
      keratomileusis (LASIK) using the VISX 20/20B and VISX Star S3 laser systems.
      METHODS: A chart review of patients who had undergone LASIK between April 1999
      and December 2001 was performed. Patients having known risk factors for
      epithelial ingrowth were excluded from the study. Both eyes of patients who were
      operated with both laser systems were included in a paired analysis. The first
      operated eyes of the remaining patients were included in an unpaired analysis.
      The outcomes studied were epithelial ingrowth (a region of epithelial growth
      under the flap that was contiguous with the flap edge and extended at least 0.7
      mm in the radial direction) and epithelial ingrowth requiring treatment
      (extending into the pupillary zone, causing reduced vision, causing nighttime
      glare, or inducing any melting of the flap edge). RESULTS: In the paired study,
      11 (61.1%) of 18 eyes treated with the VISX 20/20B had epithelial ingrowth, and 7
      (38.9%) eyes required treatment. None of the eyes treated with the VISX Star S3
      had epithelial ingrowth. In the unpaired study, 39 (37.1%) of 105 eyes treated
      with the VISX 20/20B were noted to have epithelial ingrowth and 14 (13.3%) eyes
      required treatment. None of the eyes treated with the VISX Star S3 had epithelial
      ingrowth. The incidence of epithelial ingrowth was significantly different for
      the VISX 20/20B and the VISX Star S3 in both analyses (paired: P<.001, McNemar's
      test; unpaired: P<.001, Fisher's exact test). CONCLUSIONS: The laser system used
      in LASIK is a risk factor for the development of epithelial ingrowth.

PMID- 15977886
TI  - Axial eye length evaluation before and after myopic photorefractive keratectomy.
AB  - PURPOSE: To test the accuracy of a new device (IOL Master; Carl Zeiss, Jena,
      Germany) in detecting axial eye length changes after photorefractive keratectomy
      (PRK). METHODS: Pre- and postoperative (1, 3, and 6 months) subjective refraction
      and axial eye length measurements were performed in 184 consecutive eyes that
      underwent PRK with the Nidek EC5000 excimer laser (Nidek Technologies, Gamagori,
      Japan) to treat refractive errors from +0.25 to -16.25 diopters (D) (mean: -5.12
      +/- 3.01 D). RESULTS: The axial eye length measurements ranged from 22.51 to
      31.32 mm (mean: 25.61 +/- 1.47 mm) before PRK; from 22.39 to 31.10 mm (mean:
      25.48 +/- 1.43 mm) 1 month after PRK; from 23.17 to 31.14 mm (mean: 25.61 +/-
      1.36 mm) 3 months after PRK; and from 23.36 to 29.68 mm (mean: 25.58 +/- 1.35 mm)
      6 months after PRK. Preoperative and 1-month postoperative data showed a
      statistically significant difference (P<.001), whereas no significant difference
      was found between 1 and 3 months (P=.0137) or 3 and 6 months (P=.2422).
      CONCLUSIONS: The IOL Master showed a decrease in the axial eye length measurement
      larger than the theoretical ablation depth and the difference increased as the
      correction became higher.

PMID- 15977887
TI  - Automated lamellar keratoplasty for recurrent granular corneal dystrophy after
      phototherapeutic keratectomy.
AB  - PURPOSE: To evaluate the safety and efficacy of automated lamellar keratoplasty
      for the treatment of recurrent granular corneal dystrophy after phototherapeutic
      keratectomy (PTK). METHODS: We performed a prospective interventional
      noncomparative case study of nine eyes (seven patients) with severe recurrent
      granular corneal dystrophy after PTK. An automated microkeratome was used to cut
      partial-thickness sections through the anterior surface of the donor and host
      corneas. The donor disc was placed on the recipient bed with four or eight
      interrupted sutures. The sutures were removed between 4 and 6 weeks
      postoperatively. Visual acuity, corneal clarity, corneal thickness, and corneal
      topography were assessed before and at different time points after surgery.
      RESULTS: During a mean follow-up period of 18.9 +/- 4.1 months, all grafts were
      transparent without visible opacity at the interface, and no serious
      complications occurred. In all cases, the visual acuity improved: seven eyes had
      best spectacle-corrected visual acuity of > or = 20/40; two eyes reached 20/25.
      At last follow-up > 12 months postoperatively, the mean corneal refractive power
      had significantly increased by 2.34 +/- 0.93 diopters (D) (P<.001), and the
      corneal astigmatism significantly decreased by 0.91 +/- 0.98 D (P<.05). The mean
      corneal thickness was 477.4 +/- 26.9 microm preoperatively and 507.8 +/- 23.4
      microm at last follow-up (P<.001). CONCLUSIONS: Our findings suggest that
      automated lamellar keratoplasty for the treatment of recurrent granular corneal
      dystrophy is a safe and effective method of improving visual acuity, but
      recurrence remains a risk.

PMID- 15977888
TI  - Central island treatment using Technolas 217 based on Orbscan II assessment.
AB  - PURPOSE: To present a case of central island after myopic laser in situ
      keratomileusis and the treatment technique using Technolas 217 laser based on
      topography findings. METHODS: Serial corneal topographies with Orbscan were taken
      and an ablation profile was generated with subsequent treatment using the
      phototherapeutic keratectomy mode and surface ablation technique. RESULTS: Marked
      reduction was noted in the height of central island and the best spectacle
      corrected visual acuity improved from 20/40 to 20/25. CONCLUSIONS: Ablation
      profile based on corneal topography can provide a possible treatment option for
      patients with central island.

PMID- 15977889
TI  - Management of pellucid marginal degeneration with intracorneal ring segments.
AB  - PURPOSE: To present intracorneal ring segments for potential management of
      pellucid marginal degeneration. METHODS: A 41-year-old man with pellucid marginal
      degeneration with poor visual acuity due to irregular astigmatism was treated
      with Intacs microthin insert (KeraVision, Fremont, Calif) in the left eye.
      RESULTS: Uncorrected visual acuity improved from 2/60 to 6/60 following the
      procedure. The procedure completely eliminated myopia of -8.00 diopters and
      improved the irregularity of the astigmatism, although it did not change its
      magnitude. CONCLUSIONS: Insertion of the intracorneal ring segment improves
      visual acuity in pellucid marginal degeneration by flattening the central corneal
      protrusion, thus reducing myopia and improving the astigmatism irregularity.

PMID- 15977890
TI  - Bilateral giant retinal tear following posterior chamber phakic intraocular lens
      implantation.
AB  - PURPOSE: To report a case of bilateral giant retinal tear following posterior
      chamber phakic intraocular lens (PIOL) implantation. METHODS: A patient with an
      ocular history of retinal detachment associated with giant retinal tear 4 months
      after a bilateral PIOL implantation was referred with a macula on retinal
      detachment associated with giant retinal tear in the fellow eye. The patient
      underwent vitrectomy with silicone oil tamponade and an encircling buckle. Five
      months later, a lensectomy with phakic IOL and silicone oil removal were
      performed. RESULTS: The retina was reattached and has remained stable during 3
      year follow-up. CONCLUSIONS: Although it is unclear whether retinal detachment
      associated with giant retinal tear following refractive procedures occurs within
      the normal incidence in myopic eyes, prophylactic measures are mandatory in high
      risk fellow eyes.

PMID- 15977891
TI  - Spontaneous regression of dense epithelial ingrowth after laser in situ
      keratomileusis.
AB  - PURPOSE: To present a case of dense epithelial ingrowth after laser in situ
      keratomileusis (LASIK) that spontaneously regressed 20 months after surgery.
      METHODS: A 34-year-old woman underwent bilateral LASIK. On postoperative day 1, a
      large downward displacement of the flap in the right eye was observed. The flap
      was repaired; however, epithelial ingrowth from the flap edge was noted 1 month
      later at the 1, 5, 8, and 11 o'clock positions. RESULTS: At 4-month follow-up,
      the epithelial ingrowth was stable at the 1, 8, and 11 o'clock positions but a
      dense sheet of epithelium was noted at the 5 o'clock position. At 15 months
      postoperatively, all epithelial ingrowth had resolved except for that at the 5
      o'clock position. At 20 months postoperatively, the ingrowth at the 5 o'clock
      position had also regressed. CONCLUSIONS: Dense epithelial ingrowth does not
      always require surgical intervention. Surgery is necessary only when the
      epithelium appears to be progressing, affects visual function, or causes flap
      melting.

PMID- 15977892
TI  - Pupil size in refractive surgery candidates.

PMID- 15977893
TI  - Influence of LASIK on retinal nerve fiber layer thickness.

PMID- 15977894
TI  - Epiretinal membrane formation in retinitis pigmentosa following laser in situ
      keratomileusis.

PMID- 15977895
TI  - Progenesis in digenean trematodes: a taxonomic and synthetic overview of species
      reproducing in their second intermediate hosts.
AB  - Precocious egg production, i.e. progenesis, has been documented for a number of
      species in scattered reports throughout the trematode literature. The last 2
      extensive studies on the subject date from Buttner in the early 1950s (in French)
      and from Tang in the early 1980s (in Chinese). Overall, 43 species were then
      known for their ability to produce eggs at the metacercarial stage while still in
      the second intermediate host. Here, we update the list, and document the
      existence of progenesis in a total of 79 digenean trematode species, for which we
      provide information on the taxonomy of the hosts, the facultative or obligate
      character of progenesis, relevant references, as well as some other pertinent
      biological information. We then review the subject by asking 7 questions of
      fundamental evolutionary importance. These include: What favours progenetic
      development? What are the associated costs and benefits? How are progenetic eggs
      released from the host? While exposing the various opinions of previous authors,
      we attempt to give a synthetic overview and stress on the importance of the
      metacercarial cyst wall (whether it is present, and if so its thickness) in the
      evolution and the adoption of a progenetic life-cycle.

PMID- 15977896
TI  - Culture of Neospora caninum in the presence of a Mycoplasma Removal Agent results
      in the selection of a mutant population of tachyzoites.
AB  - Mycoplasmas are common contaminants of eukaryotic cells grown in tissue culture.
      A commercially available Mycoplasma Removal Agent (MRA) was therefore assessed
      for its effect on tachyzoites of Neospora caninum, in order to determine its
      suitability for further use in parasite cell cultures. Analyses of tachyzoite and
      excreted-secreted proteins and antigens by SDS-PAGE and Western blotting show
      that MRA treatment results in the rapid selection of a mutant population that
      differs from the control and parental lines in its protein and antigen content.
      The treatment of N. caninum cultures with MRA is therefore not recommended for
      the eradication of Mycoplasma.

PMID- 15977897
TI  - Genetic homogeneity within Leishmania (L.) infantum isolated from human and dogs:
      the relationship with the sandfly fauna distribution in endemic areas of Nueva
      Esparta State, Venezuela.
AB  - Leishmania infantum has been described as a highly polymorphic group of
      parasites, responsible for visceral leishmaniasis and cutaneous leishmaniasis. In
      this paper we report the life-cycle of L. (L.) infantum in an endemic area of
      visceral leishmaniasis in Venezuela, by using molecular diagnosis and
      characterization of parasites isolated from dogs, humans with visceral
      leishmaniasis and sand flies. The molecular characterization was carried out by
      use of kDNA restriction analysis, dot-blot hybridization with species-specific
      probes and RFLP of the PCR products. The results demonstrated that L. (L.)
      infantum is the parasite responsible for VL in the island. The parasites were
      revealed to be genetically homogeneous with no intra-specific differences between
      isolates from different individuals. The highest homology of the isolates was
      with L. (L.) infantum from the Old World rather than with L. (L.) chagasi from
      the New World. Additionally, we report the geographical distribution of Lutzomyia
      longipalpis, and the relationship with the transmission of L. (L.) infantum in
      the studied area.

PMID- 15977898
TI  - Body height, body mass index, waist-hip ratio, fluctuating asymmetry and second
      to fourth digit ratio in subjects with latent toxoplasmosis.
AB  - Between 20% and 60% of the population of most countries are infected with the
      protozoan Toxoplasma gondii. Subjects with clinically asymptomatic life-long
      latent toxoplasmosis differ from those who are Toxoplasma free in several
      behavioural parameters. Case-control studies cannot decide whether these
      differences already existed before infection or whether they were induced by the
      presence of Toxoplasma in the brain of infected hosts. Here we searched for such
      morphological differences between Toxoplasma-infected and Toxoplasma-free
      subjects that could be induced by the parasite (body weight, body height, body
      mass index, waist-hip ratio), or could rather correlate with their natural
      resistance to parasitic infection (fluctuating asymmetry, 2D : 4D ratio). We
      found Toxoplasma-infected men to be taller and Toxoplasma-infected men and women
      to have lower 2D : 4D ratios previously reported to be associated with higher pre
      natal testosterone levels. The 2D : 4D ratio negatively correlated with the level
      of specific anti-Toxoplasma antibodies in Toxoplasma-free subjects. These results
      suggest that some of the observed differences between infected and non-infected
      subjects may have existed before infection and could be caused by the lower
      natural resistance to Toxoplasma infection in subjects with higher pre-natal
      testosterone levels.

PMID- 15977899
TI  - Use of micro-rotation imaging to study JNK-mediated cell survival in Theileria
      parva-infected B-lymphocytes.
AB  - Lymphocytes infected with the protozoan parasite Theileria parva are transformed
      to permanently proliferating cells, an event underlying the pathology of the
      disease. However, the molecular signalling mediating this process is complex and
      poorly understood. Here, we show that down-regulation of JNK signalling by
      transient over expression of a dominant-negative mutant of JNK (JNK-APF)
      significantly increases Annexin-V-phycoerythrin (V-PE) labelling on infected B
      cell populations observed using flow cytometry. To establish whether this
      increase was specifically due to apoptosis, we used a novel single-cell imaging
      method: micro-rotation (MR)-imaging, designed to allow high-resolution 3
      dimensional imaging of single cells in suspension. With this method we visualized
      subcellular patterns of V-PE uptake and chromatin organization in lymphocytes co
      transfected with JNK-APF and GFP-tagged histone-H2B. This single-cell approach
      allowed us to clearly reveal characteristic apoptotic phenotypes, whose patterns
      reflected progressive states of programmed cell death due to JNK down-regulation.
      Our results strongly suggest a role for JNK in the survival of Theileria-infected
      B cells, and demonstrate the powerful utility of a new and unique 3-dimensional
      imaging method for living cells in suspension.

PMID- 15977900
TI  - The impact of host starvation on parasite development and population dynamics in
      an intestinal trypanosome parasite of bumble bees.
AB  - Host nutrition plays an important role in determining the development and success
      of parasitic infections. While studies of vertebrate hosts are accumulating,
      little is known about how host nutrition affects parasites of invertebrate hosts.
      Crithidia bombi is a gut trypanosome parasite of the bumble bee, Bombus
      terrestris and here we use it as a model system to determine the impact of host
      nutrition on the population dynamics and development of micro-parasites in
      invertebrates. Pollen-starved bees supported significantly smaller populations of
      the parasite. In pollen-fed bees the parasite showed a temporal pattern in
      development, with promastigote transmission stages appearing at the start of the
      infection and gradually being replaced by choanomastigote and amastigote forms.
      In pollen-starved bees this developmental process was disrupted, and there was no
      pattern in the appearance of these three forms. We discuss the implications of
      these results for parasite transmission, and speculate about the mechanisms
      behind these changes.

PMID- 15977901
TI  - Molecular characterization of the kinetoplastid membrane protein-11 genes from
      the parasite Trypanosoma rangeli.
AB  - Trypanosomatids are early divergent parasites which include several species of
      medical interest. Trypanosoma rangeli is not pathogenic for humans but shows a
      high immunological cross-reactivity with Trypanosoma cruzi, the causative agent
      of Chagas' disease that affects more than 17 million people throughout the world.
      Recent studies have suggested that T. cruzi KMP-11 antigen could be a good
      candidate for the induction of immunoprotective cytotoxic responses against T.
      cruzi natural infection. In the present paper the genes coding for the T. rangeli
      kinetoplastid membrane protein-11 have been characterized. The results show that
      the locus encoding this protein is formed by 4 gene units measuring 550
      nucleotides in length, organized in tandem, and located in different chromosomes
      in KP1(+) and KP1(-) strains. The gene units are transcribed as a single mRNA of
      530 nucleotides in length. Alignment of the T. rangeli KMP-11 deduced amino acid
      sequence with the homologous KMP-11 protein from T. cruzi revealed an identity of
      97%. Interestingly, the T and B cell epitopes of the T. cruzi KMP-11 protein are
      conserved in the T. rangeli KMP-11 amino acid sequence.

PMID- 15977902
TI  - Effect of parasitism on plasma sex-specific proteins in Cyphocarax gilbert
      (Teleost, Curimatidae).
AB  - Cyphocarax gilbert (Szidat, L., 1948) is a fish commonly found in coastal
      drainage of eastern Brazil. This fish is sometimes caught with signs of infection
      by the crustacean Riggia paranensis, a haematophagous parasite. A remarkable
      feature of infected fish is that they lack gonads. In this paper we have analysed
      the frequency of parasitism, the gonadal development of non-infected fish and the
      profile of plasma proteins in both infected and non-infected specimens. Two
      reproductive periods/year were observed, beginning in February and August. On
      average, 40% of fish were infected, in the Itabapoana River (Brazil). Sex
      specific proteins were identified by electrophoresis. SDS-PAGE analysis
      demonstrated that a 143 kDa female-specific glycolipoprotein (FSP) is a calcium
      binding phosphoprotein. FSP was isolated through ultracentrifugation and SDS-PAGE
      analysis showed that the native protein is composed of three polypeptides of 143,
      100 and 70 kDa. Both FSP and a 33 kDa male-specific protein (MSP) are absent from
      infected fish plasma. FSP levels in female plasma changes with the developmental
      stage of gonads. Altogether these data suggest that the FSP corresponds to fish
      vitellogenin. Furthermore, the absence of the above-mentioned proteins in
      infected fish suggests that R. paranensis might interfere with the regular
      hormonal process of fish vitellogenesis.

PMID- 15977903
TI  - Disruption of a host-parasite system following the introduction of an exotic host
      species.
AB  - The potential of biological invasions to threaten native ecosystems is well
      recognized. Here we describe how an introduced species impacts on native host
      parasite dynamics by acting as an alternative host. By sampling sites across an
      invasion front in Ireland, we quantified the influence of the introduced bank
      vole (Clethrionomys glareolus) on the epidemiology of infections caused by flea
      transmitted haemoparasites of the genus Bartonella in native wood mice (Apodemus
      sylvaticus). Bartonella infections were detected on either side of the front but
      occurred exclusively in wood mice, despite being highly prevalent in both rodent
      species elsewhere in Europe. Bank vole introduction has, however, affected the
      wood mouse-Bartonella interaction, with the infection prevalence of both
      Bartonella birtlesii and Bartonella taylorii declining significantly with
      increasing bank vole density. Whilst flea prevalence in wood mice increases with
      wood mouse density in areas without bank voles, no such relationship is detected
      in invaded areas. The results are consistent with the dilution effect hypothesis.
      This predicts that for vector-transmitted parasites, the presence of less
      competent host species may reduce infection prevalence in the principal host. In
      addition we found a negative relationship between B. birtlesii and B. taylorii
      prevalences, indicating that these two microparasites may compete within hosts.

PMID- 15977904
TI  - Molecular and morphological evidence indicates that Pseudorhabdosynochus
      lantauensis (Monogenea: Diplectanidae) represents two species.
AB  - Sequences of the first internal transcribed spacer (ITS-1) and the D1-D3 domains
      of the large subunit (LSU) of the ribosomal DNA (rDNA) were determined for
      multiple specimens of 4 operational taxonomic units (OTUs) of the monogenean,
      Pseudorhabdosynochus lantauensis. OTUs were defined based on their collecting
      localities, host and/or morphological characteristics. All P. lantauensis
      specimens of one group (OTUs 1 and 3) differed in their sequences of the ITS-1
      and partial LSU rDNA when compared with specimens of a second group (OTUs 2 and
      4) by 12% and 2%, respectively. Results of the phylogenetic analyses of the LSU
      rDNA sequence data showed total (100%) bootstrap support for the separation of P.
      lantauensis into 2 distinct clades. At least 11 of the 18 nucleotide differences
      in the LSU sequence between the two P. lantauensis clades were derived (i.e.
      autapomorphic) characters when the morphologically distinct species, P.
      epinepheli and P. coioidesis, were used as outgroups. Furthermore, there were
      several autapomorphic character states for each P. lantauensis clade. This
      provides sufficient evidence to reject the null hypothesis that P. lantauensis
      represents a single species. Morphological and morphometric differences between
      these two clades provided additional strong support for the separation of P.
      lantauensis into two species. These two parasite species were found to co-exist
      on one of the two species of serranid fish (i.e. Epinephelus coioides) examined
      in the South China Sea (Guangdong Province, China).

PMID- 15977905
TI  - Epidemiology of Anguillicola crassus in the European eel (Anguilla anguilla) from
      two rivers in southern England.
AB  - European eels Anguilla anguilla from the rivers Thames and Test, in the south of
      England, were examined between 2000 and 2003 for infection with the swim-bladder
      nematode Anguillicola crassus. Since its introduction to Thames eels at tidal
      estuarine locations circa 1987, A. crassus has become established in non-tidal
      freshwater stretches upriver and data from these locations are reported for the
      first time. The prevalence of infection at Thames estuary locations was higher
      during 2000-2003 than for the period 1987-1992. By 2003, similar prevalences were
      observed at freshwater and estuarine locations, but infection intensities were
      significantly higher in freshwater. Eels from the river Test appear to have been
      recently colonized by A. crassus (circa 2000). Parasite population establishment
      within these eels was uncharacteristically slow during 2000-2001, with low
      prevalence and intensity of infection, and few gravid females during this period.
      By 2003, infection levels in Test eels were similar to those in Thames eels. The
      expansion of the A. crassus population in Test eels has occurred in the absence
      of the paratenic host ruffe Gymnocephalus cernuus, and at suboptimal pH for the
      survival and infectivity of free-living larvae. The epidemiology of A. crassus in
      Test eels demonstrates that transmission of A. crassus by ruffe is not required
      for high prevalence and intensity of infection in eels. However, the consistently
      low and atypical levels of infection in Test eels during 2000 and 2001 suggests
      that paratenic transmission by ruffe may provide a substantial contribution to
      the dynamics of A. crassus in eels in the early years following introduction, by
      facilitating the rapid increase in prevalence and intensity of A. crassus
      infection that typically occurs during this time.

PMID- 15977906
TI  - Molecular cloning and characterization of the copper/zinc and manganese
      superoxide dismutase genes from the human parasite Clonorchis sinensis.
AB  - A copper/zinc superoxide dismutase (Cu/ZnSOD) gene and a manganese superoxide
      dismutase (MnSOD) gene of the human parasite Clonorchis sinensis have been cloned
      and their gene products functionally characterized. Genes Cu/ZnSOD and MnSOD
      encode proteins of 16 kDa and 25.4 kDa, respectively. The deduced amino acid
      sequences of the two genes contained highly conserved residues required for
      activity and secondary structure formation of Cu/ZnSOD and MnSOD, respectively,
      and show up to 73.7% and 75.4% identities with their counterparts in other
      animals. The genomic DNA sequence analysis of Cu/ZnSOD gene revealed this as an
      intronless gene. Inhibitor studies with purified recombinant Cu/ ZnSOD and MnSOD,
      both of which were functionally expressed in Escherichia coli, confirmed that
      they are copper/zinc and manganese-containing SOD, respectively. Immunoblots
      showed that both C. sinensis Cu/ZnSOD and MnSOD should be antigenic for humans,
      and both, especially the C. sinensis MnSOD, exhibit extensive cross-reactions
      with sera of patients infected by other trematodes or cestodes. RT-PCR and SOD
      activity staining of parasite lysates indicate that there are no significant
      differences in mRNA level or SOD activity for both species of SOD, indicating
      cytosolic Cu/ZnSOD and MnSOD might play a comparatively important role in the C.
      sinensis antioxidant system.

PMID- 15977907
TI  - Trematode infection correlates with shell shape and defence morphology in a
      freshwater snail.
AB  - Parasitism often influences the phenotype of individuals. Many of the resulting
      changes are due to changes in resource allocation that come with infection. Here
      we examine the effect of a trematode parasite on the shape and defence morphology
      of a New Zealand freshwater snail, Potamopyrgus antipodarum. The trematode
      Microphallus sp. asexually produces hundreds of metacercarial cysts in the snail.
      The length, width and 2-dimensional area of each snail were measured. Snails were
      also assessed for their degree of spininess. Snails were dissected to determine
      gender, brooding condition and parasitism. Snails infected with Microphallus sp.
      were found to be significantly less spiny than uninfected snails. Microphallus
      infected snails were also found to have a significantly greater width to length
      ratio at larger sizes than their uninfected counterparts. These trends could be
      explained in at least 3 ways. (1) Infection causes the snails to not produce
      spines and to become wider. (2) Spiny and narrower snails are more likely to die
      when they become infected. (3) Spiny and narrower snails are more resistant to
      infection. The changes in phenotype observed are unlikely to be adaptive for
      either the host or parasite and probably represent physiological by-products of
      the host-parasite relationship.

PMID- 15977908
TI  - Host specificity and the probability of discovering species of helminth
      parasites.
AB  - Different animal species have different probabilities of being discovered and
      described by scientists, and these probabilities are determined to a large extent
      by the biological characteristics of these species. For instance, species with
      broader geographical ranges are more likely to be encountered by collectors than
      species with restricted distributions; indeed, the size of the geographical range
      is often the best predictor of a species' date of description. For parasitic
      organisms, host specificity may be similarly linked to the probability of a
      species being found. Here, using data on 170 helminth species parasitic in
      freshwater fishes, we show that host specificity is associated with the year in
      which the helminths were described. Helminths that exploit more host species, and
      to a lesser degree those that exploit a broader taxonomic range of host species,
      tend to be discovered earlier than the more host-specific helminths. This pattern
      was observed across all helminth species, as well as within the different
      helminth taxa (trematodes, cestodes, nematodes and acanthocephalans). Our results
      demonstrate that the parasite species known at any given point in time are not a
      random subset of existing species, but rather a biased subset with respect to the
      parasites' biological properties.

PMID- 15977909
TI  - Complete sequence and structure of the mitochondrial genome of the human
      tapeworm, Taenia asiatica (Platyhelminthes; Cestoda).
AB  - The complete Taenia asiatica mitochondrial genome was amplified by long extension
      polymerase chain reaction (long PCR) to yield overlapping fragments that were
      then completely sequenced. The whole mitochondrial genome was 13 703 bp long and
      contained 12 protein-encoding, 2 ribosomal RNA (small and large subunits), 22
      transfer RNA genes and a short non-coding region. Thus, its gene contents are
      like those typically found in metazoan animal mitochondrial genomes (apart from
      the absence of atp8). All the genes were transcribed from the same strand. The 3'
      end 34 bp region of nad4L overlapped with the 5' end portion of nad4. The tRNA
      genes were 61-69 bp long, and the secondary structures of 18 tRNAs had typical
      clover-leaf shapes with paired DHU arms. However, trnC, trnS1, trnS2 and trnR had
      unpaired DHU arms that were 7-12 bp in length. The tRNAs that transferred serine
      lacked a DHU arm, as is also observed in a number of parasitic platyhelminths and
      metazoans. However, the trematode trnRs have paired DHU arms. The T. asiatica
      mtDNA non-coding region was like that in other cestodes since it was composed of
      a short non-coding region of 72 nucleotides and a long non-coding region of 176
      nucleotides separated by a trnL1/, trnS2/, trnL2/, trnR/, nad5 gene cluster. The
      sequences of the cox1 genes between T. asiatica and T. saginata differ by 4.6%,
      while the T. asiatica cob gene differs by 4.1% and 12.9% from the cob genes of T.
      saginata and T. solium, respectively. In conclusion, the T. asiatica mitocondrial
      genome should provide a resource for comparative mitochondrial genomics and
      systematic studies of parasitic cestodes.

PMID- 15977910
TI  - Clinical practice guidelines in nephrology: evaluation, classification, and
      stratification of chronic kidney disease.
AB  - The National Kidney Foundation developed and oversees the Kidney Disease Outcomes
      Quality Initiative, a process that develops clinical practice guidelines in
      nephrology. Recent guidelines address the evaluation, classification, and
      stratification of chronic kidney disease (CKD). These guidelines provide, for the
      first time, a standard definition of CKD, classification of its stages, and
      suggestions for appropriate laboratory measurements for the assessment of kidney
      function. Also discussed are the association of level of kidney function with
      systemic complications that develop during CKD, and the risk of loss of kidney
      function and development of cardiovascular disease in CKD.

PMID- 15977911
TI  - Current use of nonsteroidal antiinflammatory drugs and the risk of acute
      myocardial infarction.
AB  - STUDY OBJECTIVE: To evaluate the risk of acute myocardial infarction during
      current exposure to nonsteroidal antiinflammatory drugs (NSAIDs). DESIGN:
      Retrospective case-control analysis. SETTING: General practice offices. SUBJECTS:
      A total of 8688 case patients, aged 89 years or younger, with a first-time acute
      myocardial infarction and 33,923 control subjects matched on age, sex, calendar
      time, and general practice attended. INTERVENTION: The United Kingdom General
      Practice Research Database was searched for potential cases of first-time acute
      myocardial infarction between January 1995 and April 2001. Control subjects
      without acute myocardial infarction were identified at random. MEASUREMENTS AND
      MAIN RESULTS: Exposure to NSAIDs was assessed, and 650 case patients and 2339
      control subjects were found to be currently taking NSAIDs. After adjusting for
      various risk factors for acute myocardial infarction (e.g., hypertension,
      hyperlipidemia, diabetes mellitus, ischemic heart disease, body mass index,
      smoking), the relative risk (expressed as odds ratio [OR]) of acute myocardial
      infarction was 1.07 (95% confidence interval [CI] 0.96-1.19) for subjects with
      current NSAID exposure compared with those not taking NSAIDs. The adjusted OR for
      current diclofenac use was 1.23 (95% CI 1.00-1.51), for current ibuprofen use
      1.16 (95% CI 0.92-1.46), and for current naproxen use 0.96 (95% CI 0.66-1.38)
      compared with those not taking NSAIDs. Current aspirin use combined with current
      NSAID use was associated with a statistically significant risk reduction
      (adjusted OR 0.74, 95% CI 0.57-0.97), compared with nonuse of NSAIDs and aspirin.
      Current use of aspirin together with current use of ibuprofen yielded an adjusted
      OR of 0.69 (95% CI 0.42-1.15). CONCLUSIONS: Our results provide additional
      evidence that the risk of first-time acute myocardial infarction during current
      use of NSAIDs is not materially altered. We found no evidence for a reduced
      cardioprotective effect of aspirin with concomitant NSAID use.

PMID- 15977912
TI  - Costs associated with the management of overactive bladder and related
      comorbidities.
AB  - STUDY OBJECTIVE: To evaluate the clinical and economic impact of overactive
      bladder (OAB) on the management of related comorbidities in a managed care
      population. DESIGN: Retrospective analysis of a claims database. SETTING: A large
      managed care organization in the United States. PATIENTS: A total of 11,556
      patients with OAB who were aged 18 years or older and 11,556 control subjects
      without OAB who were matched on propensity score. MEASUREMENTS AND MAIN RESULTS:
      Patients and controls were identified from July 1-December 31, 2001, and followed
      for 360 days. The propensity score for matching controls was estimated based on
      patient demographics and diagnosis of important clinical conditions during a 180
      day preindex period. Medical claims were examined for any diagnosis of the
      studied comorbidities. Submitted medical charges for claims with a primary or
      secondary diagnosis of the studied comorbidities were analyzed. Prevalence and
      medical charges for depression, skin infections, and vulvovaginitis were compared
      between patients with OAB and control subjects by using chi2 and t tests.
      Prevalence and medical charges for falls and fractures, urinary tract infections
      (UTIs), and any comorbidity were compared by using logistic regression and
      general linear modeling, to adjust for additional confounders not included in the
      matching process. Prevalence of all comorbid conditions was significantly higher
      (p<0.0001) for patients with OAB than for control subjects: falls and fractures,
      25.3% versus 16.1%; depression, 10.5% versus 4.9%; UTIs, 28.0% versus 8.4%; skin
      infections, 3.9% versus 2.3%; vulvovaginitis, 4.7% versus 1.8%; any of these
      comorbidities, 52.1% versus 27.9%. Mean annual medical charges were significantly
      higher for patients than for controls for all comorbidities: falls and fractures,
      $934 versus $598 (p<0.0001); depression, $93 versus $23 (p<0.0001); UTIs, $603
      versus $176 (p<0.0001); skin infections, $67 versus $10 (p=0.002);
      vulvovaginitis, $11 versus $3 (p<0.0001); any comorbidity, $1689 versus $829
      (p<0.0001). CONCLUSION: This study quantifies the increased prevalence of and
      additional medical costs associated with related comorbidities in patients with
      OAB, emphasizing that the economic and clinical impact of OAB extends beyond the
      disease itself. Thus, management of patients with OAB should be of greater focus
      with both clinicians and health care payers.

PMID- 15977913
TI  - Conversion from sustained-release to immediate-release bupropion: patient
      tolerability and economic impact.
AB  - STUDY OBJECTIVE: To assess patient tolerability and impact on institutional drug
      acquisition costs of converting patients from sustained-release bupropion to
      generic immediate-release bupropion. DESIGN: Retrospective medical record review.
      SETTING: Veterans Affairs medical center. PATIENTS: One hundred three outpatients
      who had been receiving sustained-release bupropion and were converted to
      immediate-release bupropion at equal individual doses and frequencies.
      MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for documentation of
      adverse effects thought to be associated with bupropion treatment; reports of
      seizure occurrence were specifically sought. Patterns of bupropion dosing were
      also assessed. Institutional drug acquisition costs were evaluated by comparing
      actual costs of bupropion for each patient before and after conversion. Adverse
      effects reported with immediate-release bupropion were those commonly associated
      with this drug (headache, agitation, chest pain, and gastrointestinal complaints)
      and were neither unusually frequent nor severe. No seizures were reported after
      the drug conversion. Mean daily doses of bupropion were not significantly
      different after conversion. Mean single doses of immediate-release bupropion were
      below 150 mg; however, six patients did receive single doses of 200 mg. After
      conversion, the annual institutional drug acquisition cost for bupropion
      decreased by approximately $48,910. CONCLUSION: Conversion from sustained-release
      bupropion to immediate-release bupropion appears to be safe. Single 200-mg doses
      of immediate-release bupropion can apparently be administered to some patients
      without inducing excessive adverse effects, including seizures. Marked reduction
      in drug acquisition costs can be achieved with this conversion.

PMID- 15977914
TI  - Gender differences in the use of peak flow meters and their effect on peak
      expiratory flow.
AB  - STUDY OBJECTIVE: To determine if gender differences in the skill of using peak
      flow meters affect peak expiratory flow (PEF). DESIGN: Prospective observational
      study. SETTING: University classroom. SUBJECTS: One hundred sixteen first-year
      pharmacy students (76 women, 40 men). INTERVENTION: Students were taught correct
      use of a peak flow meter by means of classroom discussion and demonstrations.
      MEASUREMENTS AND MAIN RESULTS: The students' technique in use of the peak flow
      meter was scored 3 times, and their PEF was recorded. Men scored higher than
      women (p=0.03) for the steps of "inhale fully" and "exhale as hard and as fast as
      you can" in the first attempt. Percentage increases in PEF did not significantly
      differ between the groups. Percentage change in PEF improved from the second
      attempt to the third attempt in women (p=0.036) but not men. On the third
      attempt, 13.2% of women versus 2.6% of men had an increase in PEF of more than
      50% (p=0.1). CONCLUSION: This study found that men learned the correct technique
      for using a peak flow meter and attained their best PEF more quickly than women.

PMID- 15977915
TI  - Can the renin-angiotensin system protect against stroke? A focus on angiotensin
      II receptor blockers.
AB  - From a patient's perspective, stroke is the most devastating form of
      cardiovascular disease, representing the number one cause of permanent disability
      in the United States. Treatment of hypertension significantly reduces the risk of
      stroke; however, it is unclear whether all antihypertensive agents are equivalent
      in this regard. Angiotensin-converting enzyme (ACE) inhibitors have been shown to
      reduce the risk of cardiovascular events, including stroke. Although attenuation
      of the renin-angiotensin system (RAS) is often credited with the blood pressure
      independent effects of this class of agents, this hypothesis has not been
      confirmed with regard to the end point of stroke. In fact, drugs that activate
      the RAS, such as diuretics and dihydropyridine calcium channel blockers, are as
      effective or superior to ACE inhibitors for stroke prevention. Angiotensin II
      receptor blockers (ARBs) selectively block the angiotensin II subtype I receptor,
      which results in a reflexive increase in levels of angiotensin II and unopposed
      activation of angiotensin II subtype 2 receptors. Clinical trials comparing ARBs
      with active controls have reported significant reductions in stroke in ARB
      treated patients. Data on ARBs and other drugs that activate the RAS (diuretics
      and dihydropyridine calcium channel blockers) support a potential role for the
      RAS in protecting against stroke. Ongoing trials with ARBs are evaluating stroke
      as a primary end point, and results should help to further elucidate the role of
      ARBs in this disease. Until then, it is prudent to treat hypertension with an
      agent or combination of agents that are likely to result in a rapid and sustained
      reduction in blood pressure, taking into consideration patient characteristics,
      comorbidities, tolerability, and cost.

PMID- 15977916
TI  - Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive
      strategies and treatment.
AB  - Oral mucositis is a frequently encountered and potentially severe complication
      associated with administration of chemotherapy and radiotherapy. Although many
      pharmacologic interventions have been used for the prevention and treatment of
      oral mucositis, there is not one universally accepted strategy for its
      management. Most preventive and treatment strategies are based on limited, often
      anecdotal, clinical data. Basic oral hygiene and comprehensive patient education
      are important components of care for any patient with cancer at risk for
      development of oral mucositis. Nonpharmacologic approaches for the prevention of
      oral mucositis include oral cryotherapy for patients receiving chemotherapy with
      bolus 5-fluorouracil, and low-level laser therapy for patients undergoing
      hematopoietic stem cell transplantation. Chlorhexidine, amifostine, hematologic
      growth factors, pentoxifylline, glutamine, and several other agents have all been
      investigated for prevention of oral mucositis. Results have been conflicting,
      inconclusive, or of limited benefit. Treatment of established mucositis remains a
      challenge and focuses on a palliative management approach. Topical anesthetics,
      mixtures (also called cocktails), and mucosal coating agents have been used
      despite the lack of experimental evidence supporting their efficacy.
      Investigational agents are targeting the specific mechanisms of mucosal injury;
      among the most promising of these is recombinant human keratinocyte growth
      factor.

PMID- 15977917
TI  - Antiinflammatory therapies for cystic fibrosis: past, present, and future.
AB  - Inflammation is a major component of the vicious cycle characterizing cystic
      fibrosis pulmonary disease. If untreated, this inflammatory process irreversibly
      damages the airways, leading to bronchiectasis and ultimately respiratory
      failure. Antiinflammatory drugs for cystic fibrosis lung disease appear to have
      beneficial effects on disease parameters. These agents include oral
      corticosteroids and ibuprofen, as well as azithromycin, which, in addition to its
      antimicrobial effects, also possesses antiinflammatory properties. Inhaled
      corticosteroids, colchicine, methotrexate, montelukast, pentoxifylline,
      nutritional supplements, and protease replacement have not had a significant
      impact on the disease. Therapy with oral corticosteroids, ibuprofen, and fish oil
      is limited by adverse effects. Azithromycin appears to be safe and effective, and
      is thus the most promising antiinflammatory therapy available for patients with
      cystic fibrosis. Pharmacologic therapy with antiinflammatory agents should be
      started early in the disease course, before extensive irreversible lung damage
      has occurred.

PMID- 15977918
TI  - Treatment of postmenopausal osteoporosis.
AB  - Osteoporosis is a major public health burden. The most devastating outcome of
      osteoporosis is fracture, which results in increased morbidity and mortality.
      These fractures most often occur in the vertebrae and indicate an increased risk
      of future vertebral and hip fractures. Consequently, it is important to identify
      patients at risk for fracture and to intervene with pharmacologic therapies,
      lifestyle changes, or both to reduce the frequency of the first or subsequent
      fracture. Moreover, because osteoporosis is a chronic condition requiring long
      term therapy, factors that increase compliance and improve safety and efficacy
      outcomes should be considered when treatment is selected. The bisphosphonates
      alendronate and risedronate can substantially reduce the risk of both hip and
      vertebral fractures. Furthermore, these agents are available in once-weekly
      formulations that provide patients with a convenient alternative to a daily
      dosage regimen. Alendronate and the selective estrogen-receptor modulator
      raloxifene provide considerable vertebral fracture protection after 1 year of
      treatment, and risedronate markedly reduces the rate of vertebral and
      nonvertebral fractures after 6 months of treatment. Data suggest that calcitonin
      salmon nasal spray also reduces the risk of vertebral, but not nonvertebral,
      fractures. Raloxifene decreases the risk of nonvertebral fracture, but only in
      women with severe prevalent vertebral fractures. Although evidence supports the
      efficacy of hormone therapy, the risks should be carefully considered before
      treatment is begun. In addition to the antiresorptive therapies, teriparatide is
      a daily injectable anabolic treatment that is effective in reducing the risk of
      vertebral and nonvertebral fractures. Therefore, clinicians and patients have
      several options for reducing the risk of fracture and achieving optimal dosing
      convenience.

PMID- 15977919
TI  - Key articles and guidelines relative to intensive care unit pharmacology--2004.
AB  - Compilations of key articles and guidelines in a particular clinical practice
      area are useful not only to clinicians who practice in that area, but to all
      clinicians. We compiled pertinent articles and guidelines pertaining to drug
      therapy in the intensive care setting from the perspective of actively practicing
      critical care pharmacists. This document differs from the original 2002 version
      in that a broader assembly of intensive care practitioners was involved in the
      compilation.

PMID- 15977920
TI  - Effects of buprenorphine on cardiac repolarization in a patient with methadone
      related torsade de pointes.
AB  - Torsade de pointes is a rare but potentially fatal ventricular arrhythmia that is
      often triggered by drugs that prolong the rate-corrected QT (QTc) interval. This
      arrhythmia has been attributed to levacetylmethadol and methadone, synthetic
      opioids used to treat heroin addiction. Levacetylmethadol, a derivative of
      methadone, is being withdrawn from the United States market because its use waned
      after a black box warning was issued to require electrocardiographic monitoring.
      Therefore, methadone and buprenorphine are the only opioids available for the
      treatment of heroin addiction. To our knowledge, the cardiac safety of
      buprenorphine in patients with methadone-related QTc prolongation has not been
      described. We report a patient who developed torsade de pointes while receiving
      high-dose methadone and was successfully inducted onto buprenorphine under close
      medical supervision. No clinically important QTc prolongation was observed in the
      acute setting or during follow-up. This observation suggests that buprenorphine
      may be a safe alternative to oral methadone in patients with opioid addiction who
      develop torsade de pointes.

PMID- 15977921
TI  - Early-onset heparin-induced thrombocytopenia after a 165-day heparin-free
      interval: case report and review of the literature.
AB  - Early- or abrupt-onset immune-mediated heparin-induced thrombocytopenia (HIT) is
      defined as HIT that occurs less than 5 days after exposure to heparin in patients
      who have received heparin within the previous 100 days. We identified no reports
      in the literature of early-onset HIT in patients who had a heparin-free interval
      longer than 100 days. However, we report a case of early-onset immune-mediated
      HIT illustrated by a positive HIT result with serotonin release and enzyme-linked
      immunosorbent assays, and a decrease in platelet count to less than 100 x
      10(3)/mm3 with no evidence of thrombosis, approximately 165 days after the
      patient's last exposure to heparin. We conclude that clinicians should choose
      alternative forms of anticoagulation in patients with even a remote history of
      HIT. If clinicians are compelled to reexpose patients to heparin, they should
      confirm a negative HIT assay result, monitor for clinical signs of HIT, and
      provide appropriate treatment if HIT is suspected.

PMID- 15977922
TI  - Tegaserod-associated ischemic colitis.
AB  - Tegaserod, a potent partial agonist of the serotonin 5-HT4 receptor, is used to
      treat women with constipation-predominant irritable bowel syndrome. Since the
      drug's approval, the manufacturer has received infrequent although serious
      reports of diarrhea and ischemic colitis in patients taking the drug. These
      instances have led to a recent warning letter to physicians and a change in the
      prescription labeling of tegaserod. We describe the development of ischemic
      colitis in a woman who was treated with tegaserod and review the relationship
      among ischemic colitis, tegaserod use, and irritable bowel syndrome. Potential
      mechanisms involved in the occurrence of ischemic colitis in patients receiving
      tegaserod are also discussed.

PMID- 15977923
TI  - Venlafaxine-associated interstitial pneumonitis.
AB  - A 55-year-old woman was hospitalized with a 7-month history of progressive
      dyspnea on exertion and hypoxia despite a normal echocardiogram. The onset of her
      symptoms correlated with a dosage increase of venlafaxine. A multichannel
      computed tomography scan showed ground-glass opacities, and an open lung biopsy
      revealed interstitial pneumonitis consistent with extrinsic allergic alveolitis.
      Venlafaxine was discontinued, and corticosteroid therapy was started; the
      patient's hypoxia improved and the infiltrates evident on chest radiographs were
      reduced. The patient continued to improve after discontinuing venlafaxine, and
      other potential etiologies for interstitial pneumonitis were excluded. Thus,
      venlafaxine may have triggered extrinsic allergic alveolitis in this patient.

PMID- 15977924
TI  - Azithromycin-warfarin interaction: are we fishing with a red herring?

PMID- 15977925
TI  - Human immunodeficiency virus and hypogonadal bone disease.

PMID- 15977926
TI  - Interviewing: content versus style.

PMID- 15977927
TI  - Advice on advice.

PMID- 15977928
TI  - Pensions a priority at RCM conference.

PMID- 15977929
TI  - Birth centres: a success story.

PMID- 15977930
TI  - Thank you, Rebecca.

PMID- 15977931
TI  - Defining and developing the birth centre.

PMID- 15977932
TI  - Against the odds: Italy's birth centre movement.

PMID- 15977934
TI  - Lights, camera... contractions.

PMID- 15977933
TI  - Supporting home birth.

PMID- 15977935
TI  - The wisdom of storks.

PMID- 15977936
TI  - Pulmonary embolism.

PMID- 15977937
TI  - Female genital mutilation.

PMID- 15977938
TI  - Valuing midwives: developing and increasing the workforce 1 March 2005.

PMID- 15977940
TI  - Listening to baby.

PMID- 15977939
TI  - Delivering integrated services for new families 3 March, Birmingham.

PMID- 15977941
TI  - How do primary care clinicians manage childhood mood and anxiety syndromes?
AB  - OBJECTIVE: To describe how primary care clinicians manage children in whom they
      diagnose mood or anxiety syndromes. METHOD: This study is a secondary analysis of
      data from the multi-site Child Behavior Study (CBS)--a cross-sectional survey of
      primary care management of psychosocial problems. The management of children in
      whom clinicians identified mood or anxiety syndromes is described and compared
      with the management of children in whom they identified other psychosocial
      problems. Recruitment for the CBS occurred in 206 primary care practices in the
      United States, Puerto Rico, and Canada from October 1994 through June 1997.
      Participants were 20,861 consecutively sampled primary care attendees aged 4-15
      years and 395 clinicians. Primary outcome measures for this report are rates of
      referral to specialized mental health care and rates of active primary care
      management (i.e., scheduling a follow-up appointment and/or providing ongoing
      counseling and/or psychotropic prescription). RESULTS: Identification of a mood
      or anxiety syndrome was associated with increased rates of referral to mental
      health compared with rates for children with other psychosocial problems. There
      was no effect on the proportion of children counseled during the visit. In fact,
      unless accompanied by a co-morbid behavioral syndrome, children receiving the
      diagnosis of a mood or anxiety syndrome were less likely to be offered a
      scheduled follow-up appointment. Rates of prescription of anti-depressants or
      anti-anxiety agents were higher for mood/anxiety groups but this was still
      uncommon (6.7%). CONCLUSIONS: Active management of childhood mood and anxiety
      syndromes in primary care was uncommon in the United States, Puerto Rico, and
      Canada in the mid-1990s.

PMID- 15977942
TI  - Perceived barriers to health care access in a treated population.
AB  - OBJECTIVE: Health care access may be a significant contributor to health outcome.
      However, few data exist on perception of barriers by patients in treatment, and
      attending a clinic visit does not mean that no barriers exist. Understanding
      barriers for treated populations is particularly important in optimizing care for
      high vulnerability populations, such as those with mental illness and the
      elderly. METHOD: A structured interview, demographic questionnaire, and SF-12
      were administered to 324 veterans presenting for primary care or mental health
      appointments at a Veterans Affairs medical center. Principle components analysis
      was performed and relationships to vulnerability characteristics were identified.
      RESULTS: Most interview items showed modest mean levels but high variance.
      Responses were stable over three to six weeks. As hypothesized, perceived total
      barriers were greater in participants from several vulnerable populations: those
      receiving treatment for mental health problems, those with disabilities, and
      those with worse physical and mental function. Minority participants did not
      perceive greater barriers. An "inverted-U" relationship with age was found.
      Principal components analysis assigned 18 items across six clinically meaningful
      subscales. Participants with mental health treatment perceived greater barriers
      in three subscales including provider communication. Curvilinear relationships
      were again seen between subscales and age. CONCLUSIONS: Even individuals "in
      care" perceive barriers. Members of vulnerable populations, particularly those
      receiving mental health treatment, perceive greater barriers. Data support a
      multi-dimensional conceptualization of perceived barriers, and different
      subgroups experience different patterns of barriers.

PMID- 15977943
TI  - Multimodal therapy of treatment resistant depression: a study and analysis.
AB  - OBJECTIVE: To demonstrate through the use of a case study, the application of
      cognitive psychotherapy in the treatment of resistant depression. METHOD: The
      case of a woman with an 18-month history of resistant depression associated with
      low self-esteem, guilt and shame, who failed to respond to three therapeutic
      trials of anti-depressants is described. A detailed description of a CBT
      intervention over 12 sessions is given. RESULT: Clear improvements on assessments
      of mood and hopelessness, along with overall improvements in social and
      occupational functioning were noted. CONCLUSION: These improvements were
      attributed to a combination of CBT and pharmacotherapy, where pharmacotherapy
      alone failed to alleviate symptoms. A concise literature review revealed
      relatively few published trials of psychological treatments, and a lack of clear
      guidelines on pharmacological treatments. More research is needed to explore the
      efficacy of psychological therapies for treatment resistant depression.

PMID- 15977944
TI  - Patient characteristics associated with participation in a practice-based study
      of depression in late life: the Spectrum study.
AB  - OBJECTIVE: An important component of generalizing study results to patients is
      the extent to which study participants adequately represent individuals targeted
      for the study. The Spectrum study of depression in older primary care patients
      was utilized to consider patient characteristics associated with
      nonparticipation. METHOD: Interviewers utilized a validated questionnaire to
      screen adults aged 65 years and older for depression who presented to one of the
      participating primary care practices in the Baltimore, Maryland area. Screening
      interviews included information about sociodemographic factors, functioning,
      health, and attitudes about depression and its treatment in order to compare
      participants with persons who declined. RESULTS: In all, 2,560 adults aged 65
      years and older were screened. Comparison of the characteristics of the patients
      who were eligible for the study (n = 773) with patients who participated fully in
      the in-home evaluation (n = 355) found that the study sample included
      proportionately more persons who: 1) were less than 80 years old; 2) completed
      high school; and 3) reported two or more visits to the practice site within six
      months of the interview. Among patients who were depressed, no significant
      differences were found in the characteristics of those who met study eligibility
      criteria and those who agreed to participate. CONCLUSIONS: Persons over the age
      of 80 years of age or those with less than a high school education may require
      tailored strategies for recruitment even when approached by a trained interviewer
      in a primary care doctor's office.

PMID- 15977945
TI  - Personality correlates related to tobacco abstinence following treatment.
AB  - OBJECTIVE: The five-factor model of personality was used to describe the
      correlates of smoking abstinence. METHODS: Following treatment in the Mayo Clinic
      Nicotine Dependence Center, the six month abstinence status was determined by
      self-report. Sixteen months to 2.4 years following the initial treatment
      evaluation, and 10 months to 1.9 years after the abstinence status was
      determined, 475 patients were mailed a Neuroticism, Extraversion, Openness, Five
      Factor Inventory questionnaire. Ninety-nine abstinent and 151 smoking patients
      returned a completed questionnaire. RESULTS: Multivariate analysis showed that
      low scores on neuroticism and openness were associated with tobacco abstinence.
      In addition, high scores on neuroticism and low scores on agreeableness and
      conscientiousness were associated with predictors of poor outcome including
      greater number of cigarettes smoked per day, initiation of smoking prior to age
      18, and a Fagerstrom Test for Nicotine Dependence score of > or = 6. CONCLUSIONS:
      Personality characteristics as predictors of smoking abstinence following
      treatment warrant further investigation in prospective clinical trails. Treatment
      matching using personality profiling as a guide may be a valuable tool for
      improving abstinence rates following treatment for nicotine dependence.

PMID- 15977946
TI  - The effect of exercise on hippocampal integrity: review of recent research.
AB  - OBJECTIVES: To review salient basic research regarding physical exercise as a
      major protective factor against hippocampal degradation and to emphasize its
      relevance to humans. METHOD: Recent mammalian and human research literature
      search and theoretical discussion. RESULTS: The cascade of cellular damages from
      oxidative stress, nitrosative stress and gluco-corticoid effects are cumulative
      and age related. Exercise training reduces oxidative stress, nitro-sative stress
      and improves neuroendocrine autoregulation which counteracts damages from stress-
      and age-related neuronal degeneration, brain ischemia and traumatic brain injury.
      Conversely, lack of exercise and motility restrictions are associated with
      increased vulnerability from oxidative stress, nitrosative stress and
      glucocorticoid excesses, all of which precede amyloid deposition and are
      fundamental in the cascade of events resulting in neuronal degradation,
      especially in the hippocampi. CONCLUSIONS: Despite the paucity of human research,
      basic animal models and clinical data overwhelmingly support the notion that
      exercise treatment is a major protective factor against neurodegeneration of
      varied etiologies. The final common pathway of degradation is clearly related to
      oxidative stress, nitrosative stress, glucocorticoid dysregulation, inflammation
      and amyloid deposition. We conclude that people prone to chronic distress, brain
      ischemia, brain trauma, and the aged are at increased risk for neurodegenerative
      diseases such as Alzheimer's. Exercise training may be a major protective factor
      but without clinical guidelines, its prescription and success with treatment
      adherence remain elusive.

PMID- 15977948
TI  - Is secretin effective in treatment for autism spectrum disorders (ASD)?

PMID- 15977947
TI  - Ziprasidone for agitation or psychosis in dementia: four cases.
AB  - OBJECTIVE: These case reports examine the potential efficacy and safety of
      ziprasidone for the treatment of agitation or psychosis in dementia. METHOD: The
      authors performed a retrospective chart review of three patients with DSM-IV
      diagnoses of dementia, treated with ziprasidone for agitation/psychosis on an
      academic psychiatric inpatient unit in 2002-2003. In addition, these three case
      reports are supplemented by a clinical report of the first outpatient with DSM-IV
      diagnosis of dementia completing a prospective open-label six-week study in 2004
      evaluating the use of oral ziprasidone for agitation/psychosis in dementia.
      Qualitative descriptions of clinical improvement provide outcome data for these
      case reports. RESULTS: Four patients with dementia with agitation/psychosis
      experienced marked behavioral improvement after receiving oral doses of
      ziprasidone (20-160 mg/day), without any evidence of problematic cardiac or other
      side-effects. Two of the four patients had final EKGs and both of these patients
      demonstrated no change of QTc interval after administration of ziprasidone.
      CONCLUSIONS: These case reports suggest that oral ziprasidone may be an effective
      and safe medication for the treatment of agitation or psychosis in patients with
      dementia.

PMID- 15977949
TI  - Personality correlates of adherence to type 2 diabetes regimens.

PMID- 15977950
TI  - Strategy for growth takes shape.

PMID- 15977951
TI  - Managing risk in device engineering.

PMID- 15977952
TI  - Northern ProCure21 scheme wins prize.
AB  - The Newcastle, North Tyneside and Northumberland Mental Health NHS Trust and the
      Laing O'Rourke Team were awarded the best practice runner-up prize at the recent
      North East Constructing Excellence Awards for their Adult Forensic Psychiatry
      Development (Phase 1) at St. Nicholas Hospital, Gosforth. Report by Rob Smith,
      estates manager at the Trust.

PMID- 15977953
TI  - Risks must be minimised.

PMID- 15977954
TI  - Multi-skilled staff will be essential.

PMID- 15977955
TI  - On-line management of PFI projects.

PMID- 15977956
TI  - Good practice in hospital hygiene.

PMID- 15977957
TI  - Ongoing regulatory compliance required.
AB  - New regulations concerning the management of asbestos in non-residential
      properties came into force in May last year, and this 'Duty to Manage'
      legislation means that duty holders should be managing their asbestos adequately
      by fulfilling certain criteria. Inadequate management of asbestos could lead to
      heavy fines. Special report by Peter Harris, client services manager, Redhill
      Analysts.

PMID- 15977958
TI  - 'Green' excellence on difficult site.

PMID- 15977959
TI  - Major challenges met in creating centre.

PMID- 15977960
TI  - Facilitating adherence to highly active antiretroviral therapy in children with
      HIV infection: what are the issues and what can be done?
AB  - Treatment of HIV infection with highly active antiretroviral therapy (HAART)
      requires sustained adherence to treatment to maintain efficacy. In pediatric
      patients, adherence to HAART represents a significant challenge for treated
      children and for their caregivers and healthcare providers. Many factors can
      affect adherence to HAART including: (i) factors related to the patient and
      his/her family; (ii) factors related to the drug/medication; and (iii) factors
      related to the healthcare system. Different strategies can be employed to tackle
      the specific obstacles identified in these three groups, and thus to facilitate
      adherence. Among the key interventions centered on the patient and his/her family
      are the tailoring of the HAART regimen to the daily activities of the child and
      his/her family, and the implementation of an intensive education program on
      adherence for the child and the caregiver, prior to starting the treatment.
      Specific medication-related problems (depending on drug pharmacokinetic and
      pharmacodynamic properties, taste and palatability, food interactions, etc.)
      exist; such problems can not be solved solely by clinicians or by families.
      Greater commitment of the pharmaceutical industry is needed, and innovative
      solutions have to be identified by clinicians in partnership with drug
      manufacturers. Furthermore, the development of an 'adherence strategy/program'
      can be recommended to all institutions working in pediatric HIV infection. Most
      of the necessary interventions to be included in such programs can be easily
      implemented, but they require trained and committed staff (and institutions), and
      time to be spent with patients and their caregivers.

PMID- 15977961
TI  - Contemporary and emerging drug treatments for urinary incontinence in children.
AB  - Pediatric incontinence is a bothersome symptom for children and their parents. It
      can have a profound influence on a child's social and psychologic development and
      well-being. It is important to understand the different disorders that result in
      incontinence and also to understand the neural influences and development on
      urinary control. Urinary leakage can be a functional or organic disorder, with
      many possible etiologies. The most common group of pediatric patients with
      incontinence are those with overactive bladder disorder. Pharmacologic therapy
      centers on the blockage of muscarinic receptors by the tertiary amines such as
      oxybutynin, tolterodine, trospium chloride, and propiverine. Although most novel
      anticholinergic medications are effective and well tolerated in children, in our
      experience oxybutynin extended release provides superior relief for urge urinary
      incontinence in children. Other agents such as alpha-adrenoceptor antagonists
      have been used with success to improve bladder empyting and decrease outlet
      resistance. Night-time voiding disorders such as primary monosymptomatic
      nocturnal enuresis tend to be symptomatically treated. One of the mainstays of
      pharmacotherapy is desmopressin, an analog to antidiuretic hormone, which
      decreases night-time urine production. Tricyclic antidepressants such as
      imipramine have also been used successfully through a combined mechanism of
      action believed to be the result of anticholinergic, antispasmodic, and
      sympathomimetic effects. Often the successful treatment of constipation also
      treats urinary incontinence or at least the symptoms of urinary leakage are
      improved. The new non-absorbable, tasteless, and odorless PEG-3350 (polyethylene
      glycol 3350) powder has quickly become a mainstay of the pharmacologic treatment
      for constipation because of its ease of preparation and favorable adverse effect
      profile. A better understanding of the physiologic control, cellular
      interactions, and second messenger signal transduction pathways has led to the
      development of many new potential target sites for pharmacologic intervention.
      The advancement of new uroselective muscarinic antagonists is currently under
      investigation for agents such as darifenacin and temiverine, which have the
      potential to improve efficacy without increasing unwanted adverse effects. New
      pharmacologic delivery systems are also being developed ranging from intravesical
      to transdermal applications to change biodistribution and improve selectivity.
      Incontinence is a significant problem for children, their parents, and their
      physicians. The changing and advancing field of pharmacotherapy has made big
      strides for symptom control in this patient population.

PMID- 15977962
TI  - Tick-borne infections in children: epidemiology, clinical manifestations, and
      optimal management strategies.
AB  - Ticks can transmit bacterial, protozoal, and viral infections to humans. Specific
      therapy is available for several of these infections. Doxycycline is the
      antimicrobial treatment of choice for all patients, regardless of age, with Rocky
      Mountain spotted fever, human monocytic ehrlichiosis, or human granulocytic
      ehrlichiosis. Chloramphenicol has been used to treat these infections in children
      but is demonstrably inferior to doxycycline. In patients with Mediterranean
      spotted fever, doxycycline, chloramphenicol, and newer macrolides all appear to
      be effective therapies. Therapy of Lyme disease depends on the age of the child
      and stage of the disease. For early localized disease, amoxicillin (for those
      aged <8 years) or doxycycline (for those aged >/=8 years) is effective.
      Doxycycline, penicillin V (phenoxymethylpenicillin) or penicillin G
      (benzylpenicillin) preparations, and erythromycin are all effective treatments
      for tick-borne relapsing fever. Hospitalized patients with tularemia should
      receive gentamicin or streptomycin. Doxycycline and ciprofloxacin have each been
      investigated for the treatment of tularemia in outpatients; however, these agents
      do not yet have established roles in the treatment of this disease in children.
      Combination therapy with clindamycin and quinine is preferred for children with
      babesiosis; the combination of azithromycin and atovaquone also appears
      promising. Ribavirin has been recently shown to markedly improve survival in
      patients with Crimean-Congo hemorrhagic fever. The role of antiviral therapy in
      the treatment of other tick-borne viral infections, including other hemorrhagic
      fevers and tick-borne encephalitis, is not yet defined.

PMID- 15977963
TI  - Gastroesophageal reflux disease in children with asthma: treatment implications.
AB  - An association between asthma and gastroesophageal reflux disease (GERD) has long
      been recognized both mechanistically and epidemiologically. The clinical
      relevance of this interplay continues to be explored, with special interest given
      to the role of GERD in the worsening of asthma. The effect of GERD is most
      frequently contemplated in patients with asthma that is difficult to control.
      Medical and surgical anti-reflux trials attempting to alter asthma symptoms have
      reported mixed but generally underwhelming results, although asthma symptom
      scores are generally improved following effective treatment of GERD. Many of the
      pharmaceutical studies can be criticised for having too short a duration or for
      likely incomplete acid suppression. Few trials have specifically studied
      pediatric populations. Because GERD is a common condition, particularly in young
      children, the role reflux plays in the worsening of asthma symptoms and the
      potential benefit on asthma of anti-reflux therapy warrants further exploration.
      Whether or not treating symptomatic GERD reduces the symptoms and severity of
      asthma in children, GERD coexisting with asthma should be aggressively treated.
      GERD symptoms in most patients with or without asthma can be controlled medically
      with continuous use of proton pump inhibitors such as omeprazole and lansoprazole
      and to a lesser extent by histamine H(2) receptor antagonists such as famotidine
      and cimetidine.

PMID- 15977965
TI  - Enoxaparin versus heparin: the SYNERGY trial from an emergency medicine
      perspective.
AB  - The SYNERGY (Superior Yield of the New strategy of Enoxaparin, Revascularisation,
      and GlYcoprotein inhibitors) trial, involving almost 10,000 patients, is a
      landmark cardiology study published in 2004. The study compared two
      anticoagulants used as part of a modern early invasive strategy involving
      angiographic triage of high-risk non-ST-elevation acute coronary syndrome
      patients. The trial as a whole showed similar efficacy between unfractionated
      heparin and enoxaparin. Regarding safety, two of the three in-hospital bleeding
      endpoints reported were similar between the two anticoagulants. Importantly,
      because of the high rate of pre-enrolment anticoagulant administration, many
      study participants required an anticoagulant change after randomisation. Thus,
      close attention is warranted to a prespecified subanalysis of >6000 patients who
      received 'consistent therapy'; that is, the same anticoagulant was administered
      pre- and post-enrolment based on intention to treat. In this large 'consistent
      therapy' cohort, the efficacy endpoint favoured enoxaparin and, as in the overall
      study population, two of the three reported bleeding endpoints were similar
      between the two anticoagulants. Finally, the rate of peri-procedural thrombotic
      complications that occurred during percutaneous coronary intervention was equal
      for both anticoagulants. Thus, since both anticoagulants have a similar efficacy
      and safety profile, then the simplicity of the enoxaparin regimen (i.e. no
      monitoring of activated partial thromboplastin time and easy dose calculation of
      1 mg/kg subcutaneously) provides an important and desirable feature relevant to a
      busy emergency medicine practitioner.

PMID- 15977964
TI  - Cardiotoxicity of cancer chemotherapy: implications for children.
AB  - Many children and adolescents with cancer receive chemotherapeutic agents that
      are cardiotoxic. Thus, while survival rates in this population have improved for
      some cancers, many survivors may experience acute or chronic cardiovascular
      complications that can impair their quality of life years after treatment. In
      addition, cardiac complications of treatment lead to reductions in dose and
      duration of chemotherapy regimens, potentially compromising clinical efficacy.
      Anthracyclines are well known for their cardiotoxicity, and alkylating agents,
      such as cyclophosphamide, ifosfamide, cisplatin, busulfan, and mitomycin, have
      also been associated with cardiotoxicity. Other agents with cardiac effects
      include vinca alkaloids, fluorouracil, cytarabine, amsacrine, and asparaginase
      and the newer agents, paclitaxel, trastuzumab, etoposide, and teniposide. The
      heart is relatively vulnerable to oxidative injuries from oxygen radicals
      generated by chemotherapy. The cardiac effects of these drugs include
      asymptomatic electrocardiographic abnormalities, blood pressure changes,
      arrhythmias, myocarditis, pericarditis, cardiac tamponade, acute myocardial
      infarction, cardiac failure, shock, and long-term cardiomyopathy. These effects
      may occur during or immediately after treatment or may not be apparent until
      months or years after treatment. Mild myocardiocyte injury from chemotherapy may
      be of more concern in children than in adults because of the need for subsequent
      cardiac growth to match somatic growth and because survival is longer in
      children. Primary prevention is therefore important. Patients should be educated
      about the cardiotoxic risks of treatment and the need for long-term cardiac
      monitoring before chemotherapy is begun. Cardiotoxicity may be prevented by
      screening for risk factors, monitoring for signs and symptoms during
      chemotherapy, and continuing follow-up that may include electrocardiographic and
      echocardiographic studies, angiography, and measurements of biochemical markers
      of myocardial injury. Secondary prevention should aim to minimize progression of
      left ventricular dysfunction to overt heart failure. Approaches include altering
      the dose, schedule, or approach to drug delivery; using analogs or new
      formulations with fewer or milder cardiotoxic effects; using cardioprotectants
      and agents that reduce oxidative stress during chemotherapy; correcting for
      metabolic derangements caused by chemotherapy that can potentiate the cardiotoxic
      effects of the drug; and cardiac monitoring during and after cancer therapy.
      Avoiding additional cardiotoxic regimens is also important in managing these
      patients. Treating the adverse cardiac effects of chemotherapy will usually be
      dependent on symptoms or will depend on the anticipated cardiovascular effects of
      each regimen. Treatments include diuresis, afterload reduction, beta-adrenoceptor
      antagonists, and improving myocardial contractility.

PMID- 15977966
TI  - Tigecycline: a novel glycylcycline.
AB  - Antibacterials have been in clinical use for almost 60 years; however, the
      effectiveness of these valuable agents has been diminished by widespread
      emergence of bacterial resistance. Tigecycline is the first in a new class of
      glycylcyclines with activity against a wide range of clinically important
      pathogens. Tigecycline has demonstrated potent microbiological activity and
      excellent therapeutic response in animal infection models and in recently
      reported phase III human clinical trials. It is effective against intra-abdominal
      and skin and soft tissue infections caused by susceptible or multidrug-resistant
      staphylococci, enterococci or streptococci as well as most Enterobacteriaceae and
      anaerobic pathogens. In clinical trials nausea and vomiting were the most common
      adverse events and were of a magnitude typical of those observed with
      tetracyclines in general. Additionally, tigecycline has proven to be efficacious
      in animal models of infection, including pneumonia, endocarditis and peritonitis.
      Tigecycline is only available as an intravenous agent and distributes extensively
      in tissues. Administration of a 100mg loading dose of tigecycline followed by
      twice-daily doses of 50mg yielded an apparent volume of distribution of 7-10
      L/kg. Systemic clearance ranged from 0.2 to 0.3 L/h/kg and its half-life varied
      from 37 to 67 hours. The pharmacokinetics of tigecycline appear unaffected by
      sex, age, renal disease or the presence of food. Data from animal studies would
      suggest that time above the minimum inhibitory concentration is the
      pharmacodynamic factor that best correlates with bacterial eradication. The
      efficacy, safety profile and pharmacodynamic attributes of tigecycline support
      its continuing clinical development as empirical parenteral treatment of
      challenging nosocomial and community-acquired infections, including those caused
      by proven or suspected resistant pathogens.

PMID- 15977968
TI  - Paediatric idiopathic inflammatory muscle disease: recognition and management.
AB  - The idiopathic inflammatory myopathies (IIM) of childhood are rare, multisystem
      autoimmune disorders, of which the most common is juvenile dermatomyositis (JDM).
      The criteria currently used to diagnose the paediatric IIMs, including both JDM
      and other childhood autoimmune conditions in which myositis may be a prominent
      feature, are somewhat outdated in relation to paediatric practice. Controversies
      surrounding the criteria for diagnosis have resulted in an international effort
      to define both the diagnostic and classification criteria in light of modern
      investigation and practice. Clinical features of these IIMs include muscle
      weakness and skin rash; however, these may be absent at disease onset. JDM
      patients require careful assessment of multiple organ systems, which can divided
      into musculoskeletal and extra-musculoskeletal, and examination should include
      validated disease measurement tools such as the Childhood Myositis Assessment
      Scale. Investigations include blood tests to assess generalised markers of
      inflammation as well as more specific markers of muscle inflammation; organ
      specific investigations, such as MRI, and muscle biopsy are also often used.
      Treatment and management protocols include corticosteroids, methotrexate and
      other disease-modifying agents such as ciclosporin (cyclosporin) and intravenous
      immunoglobulin, as well as newer treatments such as tumour necrosis factor
      blockade or B-cell depletion. Management of children with JDM requires a
      multidisciplinary approach, including specialist physiotherapy, occupational
      therapy and nursing input. Two major international projects, the International
      Myositis and Clinical Studies Group (IMACS) and Paediatric Rheumatology
      International Trials Organisation (PRINTO) aim to standardise the assessment of
      these patients and measurement of their disease. The efforts of these large
      collaborative groups should provide much needed networks for mulitcentre trials
      in the future.

PMID- 15977967
TI  - Drug treatment of pulmonary arterial hypertension: current and future agents.
AB  - During the last decade we have witnessed substantial improvements in the
      therapeutic options for pulmonary arterial hypertension (PAH), including true
      innovations targeting some of the mechanisms involved in the pathogenesis of this
      devastating disease. Intravenous epoprostenol was the first drug to improve
      symptoms and survival of patients with PAH. Novel prostanoids, including
      subcutaneous treprostinil and inhaled iloprost, also have beneficial effects in
      many patients, although their long-term efficacy is less well known. Among the
      newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase
      type 5 (PDE5) inhibitors have reshaped clinical practice. The endothelin receptor
      antagonist bosentan has been approved in many parts of the world and most current
      guidelines recommend this drug as first-line treatment for patients with PAH in
      functional class III. Novel endothelin receptor antagonists such as sitaxsentan
      sodium and ambrisentan are currently being investigated. The PDE5 sildenafil is
      also being intensively studied in patients with pulmonary hypertension, and most
      of the available data look promising, although approval for PAH is still pending.
      Other PDE5 inhibitors have not yet undergone extensive study in PAH. The
      increasing insight into the pathogenesis of PAH opens several new therapeutic
      opportunities, which include vasoactive intestinal peptide, selective serotonin
      reuptake inhibitors, adrenomedullin and HMG-CoA reductase inhibitors (statins).
      However, PAH is a complex disorder and targeting a single pathway can not be
      expected to be uniformly successful. Thus, combining substances with different
      modes of action is expected to improve symptoms, haemodynamics and survival in
      PAH patients, although combination therapy has yet to undergo the scrutiny of
      large randomised clinical trials.

PMID- 15977971
TI  - Lansoprazole oro-dispersible tablet : pharmacokinetics and therapeutic use in
      acid-related disorders.
AB  - Lansoprazole is an H+, K+-adenosine triphosphatase proton pump inhibitor (PPI)
      used for management of acid-related disorders. Lansoprazole has been reformulated
      as an oro-dispersible tablet (LODT) that quickly dissolves in the mouth without
      water. In healthy adults the safety and bioavailability of LODT 15-30 mg, taken
      without water or dispersed in water, were found to be comparable with those of
      lansoprazole 15-30 mg capsules. Moreover, the bioavailability of LODT
      administered without water has been found to be similar to that of water
      dispersed LODT given via a nasogastric tube. In a clinical study, the vast
      majority of patients found the mouth feel of LODT acceptable and almost all found
      it easy to take. A comparison of LODT with esomeprazole in a small group of
      patients with non-erosive reflux disease showed similar decreases in symptoms
      from baseline and no significant difference between groups. In conclusion, LODT
      is effective, bioequivalent to the capsule formulation and acceptable to
      patients. LODT offers an alternative dose administration method to all patients
      requiring a PPI, especially those who have difficulty swallowing, and may
      increase patient convenience and compliance.

PMID- 15977969
TI  - Acellular pertussis vaccine safety and efficacy in children, adolescents and
      adults.
AB  - This review offers a perspective on the acellular pertussis vaccine efficiency
      trials concluded in the 1990s and presents the main conclusions of a meta
      analysis of 52 studies that assessed the safety and efficacy of the diphtheria
      tetanus (DT)-whole cell pertussis (DTwP) and DT-acellular pertussis (DTaP)
      vaccines administered to children. A clear serological correlate of immunity to
      pertussis following DTaP vaccination was not identified despite an intensive
      analysis. It can be speculated that this may be because various combinations of
      antibody to agglutinogens (pertussis toxin, filamentous haemagglutinin, pertactin
      and fimbriae) provide protection, or because serum antibody levels and responses
      do not uniformly reflect mucosal IgA antibody levels.Long-term efficacy following
      DTaP vaccination is becoming characterised and cell-mediated immunity (T-cell
      memory) may have importance. DTaP vaccination appears to establish herd immunity
      after sufficient uptake within communities and countries. As experience with DTaP
      vaccine safety has accumulated, a 1-2% occurrence of large, local injection
      reactions with all products has been defined for booster doses. The
      pathophysiological mechanisms for the reactions are not established but a
      majority appear likely to be IgE-mediated reactive oedema and a minority to be
      IgG-mediated reactive Arthus-type reactions. DTwP and DTaP combinations with
      other vaccines have been studied and licensed; the most controversial combination
      products are the DTaP/Haemophilus influenzae type B polysaccharide conjugate
      vaccines. Pertussis epidemiology is changing with a clear increase in occurrence
      in adolescents and adults. This development has spurred studies and licensure of
      safer DTaP vaccines for this older population. The economic impact of pertussis
      and transmission from adults to vulnerable infants provides a cost-benefit
      justification for widespread use of DTaP vaccines in all age groups with routine
      boosting every 10 years.

PMID- 15977972
TI  - Emtricitabine: a review of its use in the management of HIV infection.
AB  - Emtricitabine (Emtriva) is an orally administered nucleoside reverse
      transcriptase inhibitor (NRTI) that is indicated in combination with other
      antiretroviral agents in the treatment of HIV infection in adults. As a component
      of antiretroviral therapy (ART), emtricitabine effectively reduces and/or
      maintains suppression of viral load in ART-naive adults or ART-experienced adults
      switching from stable combination regimens, and is generally well tolerated.
      Emtricitabine is a component of preferred initial HIV combination therapy
      regimens; it can be used in place of lamivudine as part of the dual NRTI backbone
      in non-nucleoside reverse transcriptase inhibitor (NNRTI)- and protease inhibitor
      (PI)-based regimens. Moreover, preliminary data from a randomised, open-label
      study suggest that emtricitabine plus tenofovir DF, a preferred dual-NRTI
      combination, is better tolerated than co-formulated lamivudine/zidovudine,
      another preferred dual-NRTI combination, resulting in a higher persistent
      virological response rate, as analysed using the US FDA time to loss of
      virological response (TLOVR) algorithm. With the convenience of once-daily
      (single pill) administration, no dietary restrictions and a favourable drug
      interaction and tolerability profile, emtricitabine should facilitate patient
      adherence to treatment, which, in turn, is central to the success of
      antiretroviral therapy. Similarly, emtricitabine is attractive as an option for
      ART-experienced stable adults requiring regimen simplification.

PMID- 15977970
TI  - Pharmacotherapy for obesity.
AB  - Pharmacotherapy for the management of obesity is primarily aimed at weight loss,
      weight loss maintenance and risk reduction, and has included thyroid hormone,
      amphetamines, phentermine, amfepramone (diethylpropion), phenylpropanolamine,
      mazindol, fenfluramines and, more recently, sibutramine and orlistat. These
      agents decrease appetite, reduce absorption of fat or increase energy
      expenditure. Primary endpoints used to evaluate anti-obesity drugs most
      frequently include mean weight loss, percentage weight loss and proportion of
      patients losing >or=5% and >or=10% of initial bodyweight. Secondary endpoints may
      include reduction in body fat, risk factors for cardiovascular disease and the
      incidences of diseases such as diabetes mellitus. Most pharmacotherapies have
      demonstrated significantly greater weight loss in patients on active treatment
      than those receiving placebo in short-term (<or=1 year) randomised controlled
      trials of pharmacological treatment in conjunction with a calorie-controlled diet
      or lifestyle intervention. The evidence of long-term efficacy is limited to
      sibutramine (2 years) and orlistat (4 years). These are the only drugs currently
      approved for the long-term management of obesity in adults. Sibutramine
      recipients randomised following 6 months' treatment to either sibutramine or
      placebo demonstrated significantly better weight maintenance at 2 years than
      those taking placebo (p<0.001), with >or=10% loss of initial bodyweight in 46% of
      patients. For patients taking orlistat, weight loss was 2.2 kg greater than those
      on placebo at 4 years (p<0.001), with significantly more patients achieving
      >or=10% loss of initial bodyweight (26.2% and 15.6%, respectively; p<0.001).
      Other drugs that have been evaluated for weight loss include ephedrine, the
      antidepressants fluoxetine and bupropion, and the antiepileptics topiramate and
      zonisamide. Two clinical trials with fluoxetine both reported no significant
      difference in weight loss compared with placebo at 52 weeks. Clinical trials
      evaluating ephedrine, bupropion, topiramate and zonisamide have demonstrated
      significantly greater weight loss than placebo but have been limited to 16-26
      weeks' treatment. A major obstacle to the evaluation of the clinical trials is
      the potential bias resulting from low study completion rates. Completion rates
      varied from 52.8% of phentermine recipients in a 9-month study, to 40% of
      fenfluramine recipients in a 24-week comparative study with phentermine and 18%
      of amfepramone recipients in a 24-week study. One-year completion rates range
      from 51% to 73% for sibutramine and from 66% to 85% for orlistat. Other potential
      sources of bias include run-in periods and subsequent patient selection based on
      compliance or initial weight loss. Several potential new therapies targeting
      weight loss and obesity through the CNS pathways or peripheral adiposity signals
      are in early phase clinical trials. Over the next decade the drug treatment of
      obesity is likely to change significantly because of the availability of new
      pharmacotherapies to regulate eating behaviours, nutrient partitioning and/or
      energy expenditure.

PMID- 15977973
TI  - Gliclazide modified release.

PMID- 15977974
TI  - HIPAA: how our health care world has changed.

PMID- 15977975
TI  - Caring for patients while respecting their privacy: renewing our commitment.
AB  - In 1996, HIPAA or the Health Insurance Portability and Accountability Act (HIPAA)
      was enacted into law. This law has had a significant impact on the health care
      industry including the need for numerous changes in the way we communicate with
      our patients, their families, and with each other. This law provides rights to
      patients and safeguards for employees. It affects everyone in a health care
      setting. Since the days in which the Nightingale Pledge was written, nursing has
      stressed the importance of confidentiality regarding all patient matters. The
      current Code of Ethics for Nurses ANA, 2001) is clear in intent and meaning as it
      relates to the nurse's role in promoting and advocating for patient's rights
      related to privacy and confidentiality. For nurses, HIPAA is an endorsement of
      our previously articulated responsibility to our patients. The purpose of this
      article is to remind nurses of the importance of keeping patient information
      private. This reminder will come first as HIPAA is reviewed and the implications
      of this Act for nurses is discussed. The reminder will also come as challenges to
      maintaining privacy and strategies for promoting privacy are presented.

PMID- 15977976
TI  - HIPAA: a few years later.
AB  - This article addresses the impact of the Health Insurance Portability and
      Accountability Act (HIPAA) several years after implementation. The rationale for
      HIPAA and a clarification of key terms, including covered entities, personal
      health information, and designated record sets, is reviewed. The impact of HIPAA
      at work, including increased cost and the complexities of educating employees and
      patients is assessed. Implications for homeland security, disaster planning,
      unique patient identifiers, the compilation of personal health records, and
      research are discussed.

PMID- 15977977
TI  - Notes on the tension between privacy and surveillance in nursing.
AB  - Given their 24 hour responsibility for care in many settings, nurses are the main
      arbiters of the privacy afforded or denied to patients. In this article the
      author delineates four aspects of privacy, namely: bodily privacy, space privacy,
      information privacy, and privacy of individual behaviour. He draws on a range of
      recent evidence that points to people's experiences of health care being
      unsatisfactory in terms of privacy, and offers explanations as to why much
      patient privacy is impossible. He argues that the patients' need for privacy is
      to a large extent in competition with the professional need for surveillance,
      noting that while nurses and others do maintain some patient expectations of
      privacy, these expectations are artificially low on the part of nurses, who are
      predisposed to invade privacy as an unconscious aspect of their maintenance of
      professional power. The author provides a discussion of the theoretical basis of
      this viewpoint, drawing on important insights from Foucault and Goffman, and
      concludes that an awareness of these issues can help to re-balance the tension
      between the need for privacy and the need for surveillance.

PMID- 15977978
TI  - HIPAA: past, present and future implications for nurses.
AB  - Congress enacted Health Insurance Portability and Accountability Act (HIPAA) in
      1996 to limit the ability of an employer to deny health insurance coverage to
      employees with preexisting medical conditions. The law also directed the U.S.
      Department of Health and Human Services to develop privacy rules, including, but
      not limited to, the use of electronic medical records. This law has increased
      patient privacy, but in doing so has added to the financial burden, including
      personnel costs in health care. Nurses stand at the forefront in the resolution
      of the dilemma of patient privacy versus health care expediency. The purpose of
      this article is to assist nurses and other health care professionals to better
      understand their responsibilities regarding HIPAA regulations. First, responses
      to HIPAA regulations by covered entities to date, along with responses which are
      still needed, will be described. It will be noted that HIPAA is a work in
      progress and not a specific act. Next, future initiatives having HIPAA
      implications will be presented. In conclusion, the need for all covered entities
      and their personnel to look broadly at HIPAA as initiating a new way of work in
      health care will be emphasized.

PMID- 15977979
TI  - Perspectives on suicide prevention among American Indian and Alaska native
      children and adolescents: a call for help.
AB  - Suicide rates among American Indian Alaska Native (AIAN) children and adolescents
      are the highest in the United States. Risk factors for suicide among AIAN youth
      include: strained interpersonal relationships, family instability, depression,
      low self-esteem, and alcohol use or substance abuse. Protective factors include:
      caring family relationships, supportive tribal leaders, and positive school
      experiences. Carefully planned, culturally sensitive, comprehensive programs that
      address the social determinants of health outcomes such as poverty, school
      failure, familial conflicts, and limited access to health care, should be the
      focus of blueprints for change for these vulnerable children. Moreover,
      culturally competent providers are key elements associated with reducing the
      suicide rates among AIAN children and adolescents.

PMID- 15977980
TI  - Exercise and cancer recovery.
AB  - Disease and cancer treatment-related side effects such as decreased energy level,
      muscle weakness, and declines in functional status and body mass have been well
      documented. There is evidence that exercise, such as low intensity aerobics
      walking, Tai Chi, or cycling, results in an overall decrease in fatigue levels
      over the course of cancer treatment. Additionally, there is evidence that regular
      physical activity or exercise can decrease emotional stress, blood pressure, the
      duration of neutropenia, thrombocytopenia, and pain. Exercise also has been shown
      to increase quality of life and improve the maximal oxygen uptake during
      exertion, sleep patterns, and cognition. However, the majority of studies of
      exercise and cancer have been conducted with women with early stage breast
      cancer, limiting the generalizability of these studies to other cancer
      populations. The purpose of this systematic review is to provide a synthesis of
      the extant research evidence about th e benefits of exercise related to cancer
      recovery.

PMID- 15977981
TI  - Google extends its reach.

PMID- 15977982
TI  - Health care report cards: pass or fail?

PMID- 15977983
TI  - Obesity: from a health issue to a political and policy issue.

PMID- 15977985
TI  - Current advances on different kinases involved in tau phosphorylation, and
      implications in Alzheimer's disease and tauopathies.
AB  - Hyperphosphorylation and accumulation of tau in neurons (and glial cells) is one
      the main pathologic hallmarks in Alzheimer's disease (AD) and other tauopathies,
      including Pick's disease (PiD), progressive supranuclear palsy, corticobasal
      degeneration, argyrophilic grain disease and familial frontotemporal dementia and
      parkinsonism linked to chromosome 17 due to mutations in the tau gene (FTDP-17
      tau). Hyperphosphorylation of tau is regulated by several kinases that
      phosphorylate specific sites of tau in vitro. GSK-3-immunoprecipitated sarcosyl
      insoluble fractions in AD have the capacity to phosphorylate recombinant tau. In
      addition, GSK-3 phosphorylated at Ser9, that inactivates GSK-3, is found in the
      majority of neurons with neurofibrillary tangles and dystrophic neurites of
      senile plaques in AD, and in Pick bodies and other phospho-tau-containing neurons
      and glial cells in other tauopathies. Increased expression of active kinases,
      including stress-activated kinase, c-Jun N-terminal kinase (SAPK/JNK) and kinase
      p38 has been found in brain homogenates in all the tauopathies. Strong active
      SAPK/JNK and p38 immunoreactivity has been observed restricted to neurons and
      glial cells containing hyperphosphorylated tau, as well as in dystrophic neurites
      of senile plaques in AD. Moreover, SAPK/JNK- and p38-immunoprecipitated sub
      cellular fractions enriched in abnormal hyperphosphorylated tau have the capacity
      to phosphorylate recombinant tau and c-Jun and ATF-2 which are specific
      substrates of SAPK/JNK and p38 in AD and PiD. Interestingly, increased expression
      of phosphorylated (active) SAPK/JNK and p38 and hyperphosphorylated tau
      containing neurites have been observed around betaA4 amyloid deposits in the
      brain of transgenic mice (Tg 2576) carrying the double APP Swedish mutation.
      These findings suggest that betaA4 amyloid has the capacity to trigger the
      activation of stress kinases which, in turn, phosphorylate tau in neurites
      surrounding amyloid deposits. Complementary findings have been reported from the
      autopsy of two AD patients who participated in an amyloid-beta immunization trial
      and died during the course of immunization-induced encephalitis. The
      neuropathological examination of the brain showed massive focal reduction of
      amyloid plaques but not of neurofibrillary degeneration. Activation of SAPK/JNK
      and p38 were reduced together with decreased tau hyperphosphorylation of aberrant
      neurites in association with decreased amyloid plaques in both Tg2576 mice and
      human brains. These findings support the amyloid cascade hypothesis of tau
      phosphorylation mediated by stress kinases in dystrophic neurites of senile
      plaques but not that of neurofibrillary tangles and neuropil threads in AD.

PMID- 15977986
TI  - Protein aggregation in Alzheimer's disease and other neoropathological disorders.
AB  - A conspicuous feature shared by Alzheimer's disease as well as a variety of
      highly prevalent, clinically unrelated neurodegenerative disorders is the
      occurrence of protein aggregates both intra- and extracellularly. Most of these
      conditions are characterized at autopsy by the presence of such deposits,
      typically of fibrillar structure and accompanying extensive neuronal cell loss,
      displaying a selective brain distribution. The recently discovered similarities
      of a number of these aggregates with a novel type of experimentally induced
      protein deposit, formed as a general response to discrepancies in protein
      turnover and designated the "aggresome", has prompted speculations about the
      involvement of the ubiquitin-proteasome system in a process fundamental to
      neurodegeneration. Consistent with this view, protein aggregates have been
      regarded in a pathogenic connotation, with most aspects of neurologic
      pathogenesis being largely attributed to their presence in nerve tissues.
      However, the neurotoxicity of protein aggregates remains ambiguous as direct
      evidence substantiating it have long remained elusive. A convergence of evidence
      now support the notion that the actual culprits might comprise the oligomeric,
      non-fibrillar intermediates that arise early during the aggregation process,
      termed protofibrils and that the fibrillar end-stage aggregates themselves might
      actually serve a neuroprotective function. These intermediates ostensibly resolve
      many puzzling aspects of neurodegeneration and there is evidence that
      neurotoxicity is one key operational property they may possess. The above attest
      to the fact that protein aggregation remains a complex issue with a role far more
      enigmatic than originally thought but nonetheless important for the understanding
      of the pathological basis of neurodegenerative disorders.

PMID- 15977987
TI  - The role of the brain renin-angiotensin system in neurodegenerative disorders.
AB  - The primary function of the renin-angiotensin system (RAS) is to maintain fluid
      homeostasis and regulate blood pressure. Several components of the RAS, namely
      angiotensinogen, angiotensin converting enzyme, angiotensin II and their
      receptors, are found in the CNS suggesting the possibility of a localized RAS in
      the brain. Cognitively disabling neurodegenerative disorders such as Alzheimer's
      disease or vascular dementia show vascular lesions, and the brain RAS has been
      suggested to contribute to the disease process. The aim of this brief review is
      to summarize the current state of research in this field with emphasis on RAS
      related alterations during the course of neurodegenerative disorders.

PMID- 15977988
TI  - Transgenic C. elegans as a model in Alzheimer's research.
AB  - Alzheimer's disease (AD) has been associated with aggregation of beta-amyloid
      peptide (Abeta) and cell death in the brain. Using various models, such as the
      nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the
      mouse Mus musculus, investigators have attempted to imitate the pathology process
      of AD for better understanding of the cellular mechanisms and for possible
      therapeutic intervention. Among many in vitro and in vivo models of AD,
      transgenic C. elegans expressing human Abeta has shown its own advantages. The
      transgenic C. elegans model have been used in studying AD due to its short life
      span, facility to maintain, ability to develop muscle-associated deposits
      reactive to amyloid-specific dyes and the concomitant progressive paralysis
      phenotype. Moreover, the transgenic C. elegans exhibits increased levels of
      reactive oxygen species (ROS) and protein carbonyls, similar to those observed in
      AD patients, supporting the current theory on Abeta-induced oxidative stress and
      subsequent neurodegeneration in AD. DNA microarray assays of the worm
      demonstrated several stress-related genes being upregulated, particularly two
      genes homologous to human alphaB-crystallin and tumor necrosis factor-related
      protein, which were also upregulated in postmortem AD brain. Studies in our
      laboratory along with others suggest that the transgenic C. elegans model is a
      suitable in vivo model to relate Abeta-expression with its toxicity, which may
      underlie AD pathology. It may also be used as a tool for pharmacological
      evaluation of novel therapeutic agents.

PMID- 15977989
TI  - Biochemical markers and risk factors of Alzheimer's disease.
AB  - As the spectrum of therapeutic options broadens, the possibility of an early and
      accurate diagnosis of Alzheimer's disease (AD), or even isolation of a group at
      high risk of subsequent cognitive decline, is focusing widespread attention.
      Therefore, biological markers or risk factors of AD are highly desirable. In this
      work, we give an overview of the most extensively studied AD biomarkers, namely
      beta-amyloid, tau protein, and phosphorylated tau-protein, alone or in
      combination. Moreover, we describe the role of inflammatory markers (cytokines,
      acute phase proteins), oxidative stress markers (isoprostanes, 8-hydroxyguanine,
      3-nitrotyrosine, plasma antioxidants, redox transition metals), homocysteine and
      related vitamins, cholesterol and 24S-hydroxycholesterol in the diagnostic
      process or prediction of AD. We briefly review less popular, though promising
      markers of AD - markers of apoptosis, neuronal thread protein, acetyl- and
      butyrylcholinesterase, sulfatide, kallikreins, matrix-degrading
      metalloproteinases, and novel isoforms of beta-amyloid and tau. Finally, we
      discuss the clinical applicability of AD-related biological markers.

PMID- 15977990
TI  - Lipid alterations in the earliest clinically recognizable stage of Alzheimer's
      disease: implication of the role of lipids in the pathogenesis of Alzheimer's
      disease.
AB  - Lipids have many important yet distinct functions in cellular homeostasis such as
      forming an impermeable barrier separating intracellular and extracellular
      compartments, providing a matrix for the appropriate interactions of membrane
      associated proteins, and serving as storage reservoirs for biologically active
      second messengers. Alterations in cellular lipids may therefore result in
      abnormal cellular functions. This review summarizes the results from the
      examination of lipid alterations in Alzheimer's disease (AD). In addition to the
      effects of cholesterol on AD, substantial depletions of plasmalogen and sulfatide
      as well as dramatic increases in ceramide are specifically manifested at the
      earliest clinically recognizable stage of AD. The potential mechanism(s)
      underlying these changes and the potential consequences of these changes in
      neuronal function and in AD development are also discussed. Collectively, this
      review will provide an overview of the lipid alterations in Alzheimer's disease
      and the relationship of these lipid alterations with the development of AD
      pathogenesis.

PMID- 15977991
TI  - Alzheimer's disease and neural transplantation as prospective cell therapy.
AB  - It has long been recognised that Alzheimer's disease (AD) patients present an
      irreversible decline of cognitive functions as consequence of cell deterioration
      in the forebrain cholinergic projection system (FCPS), particularly, in a
      structure called nucleus basalis of Meynert (nbM). The reduction of the number of
      cholinergic cells in the FCPS disrupts not just its functions and direct
      connexions but also the modulation of other systems causing interference in
      several aspects of behavioural performance including arousal, attention, learning
      and emotion. It is also common knowledge that AD is an untreatable degenerative
      disease with very few temporary and palliative drug therapies. Neural stem cell
      (NSC) grafts present a potential and innovative strategy for the treatment of
      many disorders of the central nervous system including AD, with the possibility
      of providing a more permanent remedy than present drug treatments. After
      grafting, these cells have the capacity to migrate to lesioned regions of the
      brain and differentiate into the necessary type of cells that are lacking in the
      diseased brain, supplying it with the cell population needed to promote recovery.
      The present article aims to review the main aspects of Alzheimer's disease and to
      explore the use of neural stem cells grafts as alternative treatment for the
      consequent functional deterioration.

PMID- 15977993
TI  - An outline of the role of anti-Candida antibodies within the context of passive
      immunization and protection from candidiasis.
AB  - The role played by antibodies (Abs) in the anticandidal defense has long been a
      matter of controversy, mostly due to the past inability to clearly define antigen
      specificity, the relationship between the type of immune response within the
      different settings of experimental and human candidiasis and, last but not least,
      a misunderstanding about the role of T helper cell in cell-mediated versus the
      humoral immunity. Contributory was also the lack of precise identification of
      virulence traits of the fungus which are the best candidates for a protective Ab
      response. In recent years, an impressive amount of experimental evidence, and
      also some clinical proof, have been generated which assign to Abs of defined
      specificity an important role in the anticandidal defense both at systemic and
      mucosal sites. Paradigmatic among them, Abs against defined virulence factors
      such as adhesins or aspartyl-proteinase enzymes, or against critical viability
      molecules such as beta-glucan, have been detected or generated which hold great
      promise for immunotherapeutic interventions in humans.

PMID- 15977994
TI  - Defining criteria for anti-mannan antibodies to protect against candidiasis.
AB  - Prevention of hematogenously disseminated candidiasis and mucocutaneous disease,
      including Candida vaginitis, through immunological approaches is appealing for
      the following reason. A long-acting and safe vaccine that protects against both
      serotypes of Candida albicans and other important species, such as C. tropicalis
      and C. glabrata, should significantly reduce the incidence of various forms of
      candidiasis by these etiologic agents. Through extensive experimentation on
      protective responses in experimental animals against Candida mannan components,
      others and we have evidence that antibodies specific for short-chain beta-linked
      oligomannosides are protective against candidiasis. Although the mechanism of
      protection against vaginal infection requires further investigation,
      experimentally the ability of antibody to rapidly deposit high amounts of
      complement factor C3 onto the yeast cell wall is requisite for enhancing
      resistance against disseminated candidiasis.

PMID- 15977995
TI  - Antifungal and antitumor activities of a monoclonal antibody directed against a
      stress mannoprotein of Candida albicans.
AB  - Immunization of mice with a stress mannoprotein of >200 kDa from the cell wall of
      Candida albicans led to the production of monoclonal antibody (Mab) C7. The
      immunogen is a major target of secretory IgA and its expression is regulated by
      different environmental conditions including temperature, pH, glucose
      concentration and ammonium sulphate in the culture medium. Mab C7 reacted with a
      peptide epitope present in the >200 kDa antigen as well as in a number of
      antigens from the blastoconidium and germ tube cell wall, including enolase. In
      addition to its reactivity with C. albicans, Mab C7 also reacted with antigens
      present in C. krusei, C, tropicalis, C. glabrata, C. dubliniensis and C.
      lusitaniae, as well as in Cryptococcus neoformans, Scedosporium prolificans and
      Aspergillus fumigatus. Mab C7 exhibited four important biological activities,
      namely inhibition of adhesion of C. albicans to a variety of surfaces, inhibition
      of germination of C. albicans, direct candidacidal activity and direct
      tumoricidal activity. In tumor cells, Mab C7 reacted with nucleoporin Nup88, a
      reactivity that can be utilized for diagnostic and prognostic purposes.

PMID- 15977996
TI  - Human recombinant antibody to HSP90: a natural partner in combination therapy.
AB  - Recent years have seen the development of the concept of combination therapy for
      treating severe fungal sepsis. The advantages of this approach are a potential
      improvement in patient survival and a reduction in the chance of resistance
      developing to each of the single agents. The disadvantage is that combining drugs
      may increase the chance of toxicity. Mycograb is a genetically recombinant
      antibody against fungal heat shock protein 90 (hsp90) which is poised to become
      the mainstay of combination therapy. This paper presents data on how hsp90 is
      important to fungi and what role it might play in human disease with possible
      interactions with interleukin 6 and nitric oxide. There is discussion of
      preclinical data demonstrating synergy in vitro between Mycograb and amphotericin
      B and caspofungin. The progress of Mycograb through a Phase II pharmacokinetic
      study when used in escalating doses with a liposomal amphotericin B preparation
      has also been reviewed. The concepts behind a Phase II pivotal study, where
      Mycograb or a placebo was given in combination with a liposomal amphotericin B
      drug for five days for the treatment of disseminated candidiasis are discussed.

PMID- 15977997
TI  - The cellular responses induced by the capsular polysaccharide of Cryptococcus
      neoformans differ depending on the presence or absence of specific protective
      antibodies.
AB  - The capsule of Cryptococcus neoformans, the principal virulence factor of this
      fungus, is composed primarily of polysaccharide. The predominant component of the
      polysaccharide capsule is glucuronoxylomannan (GXM), a compound with potent
      immunoregulatory properties. GXM is bound and internalized by natural immune
      cells affecting innate and subsequent adaptive immune response. The cellular
      pattern recognition receptors involved in GXM binding include toll-like receptor
      (TLR)4, CD14, TLR2, CD18, Fc gamma receptor II (FcgammaRPi). This multiple cross
      linking leads to a suppressive outcome that is arrested and even reversed by
      protective antibodies to GXM. This review analyzes the immunosuppressive effects
      induced by capsular material, considering its pattern recognition receptors, and
      dissects the mechanism of monoclonal antibody shifting to immunoactivation.

PMID- 15977998
TI  - Insights into mechanisms of antibody-mediated immunity from studies with
      Cryptococcus neoformans.
AB  - At first glance Cryptococcus neoformans appears an unlikely microbe to provide a
      new understanding of mechanisms of antibody-mediated immunity (AMI), because it
      is a facultative intracellular fungal pathogen for which the role of naturally
      acquired AMI in host defense is uncertain. However, numerous studies have now
      established that certain antibodies (Abs) against C. neoformans are protective in
      certain hosts. Studies with Abs to C. neoformans have provided new insights into
      AMI and generated new precedents with implications for other pathogens. The
      following concepts have emerged: 1) susceptibility to C. neoformans may be
      related to qualitative and quantitative aspects of the Ab response; 2) protective
      monoclonal Abs can be generated against pathogens even when the role of humoral
      immunity is uncertain; 3) Abs to C. neoformans mediate protection by
      immunomodulatory effects, thereby linking Ab efficacy to the overall host immune
      response; 4) Ab efficacy is critically dependent on fine specificity, which in
      turn is affected by immunoglobulin variable region usage, somatic mutation and
      constant region usage; 5) the efficacy of passive Ab therapy is a function of Ab
      dose and infecting innoculum, with lack of efficacy at the extremes of Ab
      concentration; 6) Ab-mediated toxicity resulting from antigen-Ab complex-induced
      release of platelet activating factor is isotype dependent. Observations with C.
      neoformans have stimulated a reappraisal of the role of humoral immunity for
      other pathogens and highlighted the limitations in current methods of assessing
      the role of Ab in host defense.

PMID- 15977999
TI  - Protective antibodies and endemic dimorphic fungi.
AB  - The host response to infection is the outcome of a complex interaction between a
      microbe and a host's innate and adaptive immune system. In this context, the role
      of antibody in the endemic mycoses is relatively poorly understood. Recently, a
      monoclonal antibody to a cell surface protein has been shown to be protective in
      a murine histoplasmosis model. The findings with Histoplasma capsulatum may
      provide a paradigm for antibody protection against endemic fungi. This paper
      reviews the recent data on protective antibody in histoplasmosis and previous
      data supporting a role for antibody in protective responses in other dimorphic
      fungi.

PMID- 15978000
TI  - Protective antifungal yeast killer toxin-like antibodies.
AB  - After several years of controversy, antibodies (Abs) are now believed to play an
      important role in the protection against fungal infections. Among them, recent
      data are strongly supporting the relevance of protective yeast killer toxin-like
      Abs ("antibiobodies", KT-Abs), which are able to exert a direct microbicidal
      activity by mimicking a killer toxin (PaKT) and its interaction with cell wall
      receptors on susceptible cells essentially constituted by beta-glucans. This
      review will focus on the implications of the yeast killer phenomenon, and,
      particularly, the occurrence and antimicrobial activity of protective antifungal
      KT-Abs, such as those produced during the course of experimental and natural
      infections caused by PaKT-sensitive microorganisms or produced by idiotypic
      vaccination with a PaKT-neutralizing mAb. The strong therapeutic activity exerted
      against different experimental mucosal and systemic mycoses by monoclonal and
      recombinant microbicidal KT-Abs (either in their soluble forms or expressed on
      human commensal bacteria) as well as by a synthetic killer peptide (KP, an
      antibody fragment engineered from the sequence of a recombinant KT-Ab) will be
      discussed. The surprisingly wide antimicrobial spectrum of activity against
      eukaryotic and prokaryotic pathogenic agents, such as fungi, bacteria and
      protozoa, of these Abs and Ab-derived molecules suggests new potential strategies
      for transdisease anti-infective prevention and therapy.

PMID- 15978001
TI  - A role for nitric oxide in sensory-induced neurogenesis in an adult insect brain.
AB  - In the adult cricket, neurogenesis occurs in the mushroom bodies, the main
      integrative structures of the insect brain. Mushroom body neuroblast
      proliferation is modulated in response to environmental stimuli. However, the
      mechanisms underlying these effects remain unspecified. In the present study, we
      demonstrate that electrical stimulation of the antennal nerve mimics the effects
      of olfactory activation and increases mushroom body neurogenesis. The putative
      role of nitric oxide (NO) in this activity-regulated neurogenesis was then
      explored. In vivo and in vitro experiments demonstrate that NO synthase
      inhibition decreases, and NO donor application stimulates neuroblast
      proliferation. NADPH-d activity, anti-L-citrulline immunoreactivity, as well as
      in situ hybridization with a probe specific for Acheta NO synthase were used to
      localize NO-producing cells. Combining these three approaches we clearly
      establish that mushroom body interneurons synthesize NO. Furthermore, we
      demonstrate that experimental interventions known to upregulate neuroblast
      proliferation modulate NO production: rearing crickets in an enriched sensory
      environment induces an upregulation of Acheta NO synthase mRNA, and unilateral
      electrical stimulation of the antennal nerve results in increased L-citrulline
      immunoreactivity in the corresponding mushroom body. The present study
      demonstrates that neural activity modulates progenitor cell proliferation and
      regulates NO production in brain structures where neurogenesis occurs in the
      adult insect. Our results also demonstrate the stimulatory effect of NO on
      mushroom body neuroblast proliferation. Altogether, these data strongly suggest a
      key role for NO in environmentally induced neurogenesis.

PMID- 15978002
TI  - A bipotent neural progenitor cell line cloned from a cerebellum of an adult p53
      deficient mouse generates both neurons and oligodendrocytes.
AB  - Here we report developmental characteristics of a clonal cell line 2Y-3t
      established from a multifocal neoplasm that arose in a cerebellum of an adult p53
      deficient mouse. The tumorigenicity of the line was not observed in soft agar
      assay or in nude mouse assay. In serum-containing medium, 2Y-3t cells were
      epithelial-like in morphology and were mitotic. When they were cultured in serum
      free medium, the expressions of neural stem and/or progenitor cell markers were
      decreased. Concomitantly, the expressions of neuronal and oligodendrocyte markers
      were increased in concert with morphological differentiation, and DNA synthesis
      ceased. None of astrocyte markers were detected under these culture conditions.
      Double-labelling studies revealed that two cell populations coexisted, expressing
      neuronal or oligodendrocyte markers. Triiodothyronine (T3) increased the
      oligodendrocyte population when 2Y-3t cells were cultured in serum-free medium.
      Recloning of the line gave rise to three types of subclones. Sixteen subclones
      were capable of generating both neurons and oligodendrocytes, four subclones were
      capable of generating only neurons and one subclone was capable of generating
      only oligodendrocytes. Thus, 2Y-3t cells have characteristics of bipotent neural
      progenitor cells capable of generating both neurons and oligodendrocytes. In
      addition, the line expressed mRNA for Pax-2 and had GAD67-positive cells when
      cultured in serum-free medium. However, none of the mRNAs for Zic-1, Math1,
      zebrin or Calbindin-D28k were detected, suggesting that the 2Y-3t line might
      generate the GABAergic interneuron lineage of the mouse cerebellum.

PMID- 15978003
TI  - Involvement of the nitric oxide-cyclic GMP pathway and neuronal nitric oxide
      synthase in ATP-induced Ca2+ signalling in cochlear inner hair cells.
AB  - We recently demonstrated that extracellular adenosine 5'-triphosphate (ATP)
      induced nitric oxide (NO) production in the inner hair cells (IHCs) of the guinea
      pig cochlea, which inhibited the ATP-induced increase in the intracellular Ca(2+)
      concentrations ([Ca(2+)](i)) by a feedback mechanism [Shen, J., Harada, N. &
      Yamashita, T. (2003) Neurosci. Lett., 337, 135-138]. We herein investigated the
      role of the NO-cGMP pathway and neuronal NO synthase (nNOS) in the ATP-induced
      Ca(2+) signalling in IHCs using the Ca(2+)-sensitive dye fura-2 and the NO
      sensitive dye DAF-2. Fura-2 fluorescence-quenching experiments with Mn(2+) showed
      that ATP triggered a Mn(2+) influx. L-N(G)-nitroarginine methyl ester (L-NAME), a
      nonspecific NOS inhibitor, accelerated the ATP-induced Mn(2+) influx while S
      nitroso-N-acetylpenicillamine (SNAP), a NO donor, suppressed it. 1H
      [1,2,4]oxadiazole[4,3-a] quinoxalin-1-one, an inhibitor of guanylate cyclase, and
      KT5823, an inhibitor of cGMP-dependent protein kinase, enhanced the ATP-induced
      [Ca(2+)](i) increase. 8-Bromoguanosine-cGMP, a membrane-permeant analogue of cGMP
      mimicked the effects of SNAP. Moreover, the effects of 7-nitroindazole, a
      selective nNOS inhibitor, mimicked the effects of L-NAME regarding both the
      enhancement of the ATP-induced Ca(2+) response and the attenuation of NO
      production. Immunofluorescent staining of nNOS using a single IHC revealed that
      nNOS was distributed throughout the IHCs, but enriched in the apical region of
      the IHCs as shown by intense staining. In conclusion, the ATP-induced Ca(2+)
      influx may be the principal source for nNOS activity, which may interact with P2X
      receptors in the apical region of IHCs. Thereafter, NO can be produced and
      conversely inhibits the Ca(2+) influx via the NO-cGMP-PKG pathway by a feedback
      mechanism.

PMID- 15978004
TI  - Loss of forebrain cholinergic neurons and impairment in spatial learning and
      memory in LHX7-deficient mice.
AB  - The identification of the genetic determinants specifying neuronal networks in
      the mammalian brain is crucial for the understanding of the molecular and
      cellular mechanisms that ultimately control cognitive functions. Here we have
      generated a targeted allele of the LIM-homeodomain-encoding gene Lhx7 by
      replacing exons 3-5 with a LacZ reporter. In heterozygous animals, which are
      healthy, fertile and have no apparent cellular deficit in the forebrain, b
      galactosidase activity reproduces the pattern of expression of the wild-type Lhx7
      locus. However, homozygous mutant mice show severe deficits in forebrain
      cholinergic neurons (FCNs), while other classes of forebrain neurons appear
      unaffected. Using the LacZ reporter as a marker, we show that in LHX7-deficient
      mice FCN progenitors survive but fail to generate cholinergic interneurons in the
      striatum and cholinergic projection neurons in the basal forebrain. Analysis of
      behaviour in a series of spatial and non-spatial learning and memory tasks
      revealed that FCN ablation in Lhx7 mutants is associated with severe deficits in
      spatial but only mild impairment of non-spatial learning and memory. In addition,
      we found no deficit in long-term potentiation in mutant animals, suggesting that
      FCNs modulate hippocampal function independently of its capacity to store
      information. Overall our experiments demonstrate that Lhx7 expression is required
      for the specification or differentiation of cholinergic forebrain neurons
      involved in the processing of spatial information.

PMID- 15978005
TI  - Characterization of organotypic ventral mesencephalic cultures from embryonic
      mice and protection against MPP toxicity by GDNF.
AB  - We characterized organotypic ventral mesencephalic (VM) cultures derived from
      embryonic day 12 (E12) mice (CBL57/bL6) in terms of number of dopaminergic
      neurons, cell soma size and dopamine production in relation to time in vitro and
      tested the effects of 1-methyl-4-phenylpyridinium (MPP(+)) and glial derived
      neurotrophic factor (GDNF) to validate this novel culture model. Dopamine
      production and dopaminergic neuron soma size increased dramatically with time in
      vitro, whereas the number of dopamine neurons declined by approximately 30%
      between week 1 and week 2, which was further reduced after week 4. GDNF treatment
      (100 ng/mL) increased dopaminergic neuron soma size (up to 43%) and DOPAC
      production (approximately three-fold), but not the number of dopamine neurons in
      control cultures. One-week-old cultures were more vulnerable to MPP(+), than
      three-week-old cultures. The EC(50) for dopamine depletion after 2 days exposure
      and 15 days of recovery were 0.6 and 7 microm, respectively. Both pre-treatment
      and post-treatment with GDNF are important to obtain maximal protection against
      MPP(+) toxicity. In one-week-old cultures (5 microm MPP(+), 2 days) GDNF provided
      potent neuroprotection with dopamine contents reaching control levels and number
      of tyrosine hydroxylase (TH)(+) cells up to 80% of control, but in three-week-old
      cultures (10 microm MPP(+), 2 days) the protective potential of GDNF was markedly
      reduced. Long recovery periods after MPP(+) exposure are required to distinguish
      between reversible or irreversible toxic and/or trophic effects.

PMID- 15978006
TI  - The chemokine CCL2 modulates Ca2+ dynamics and electrophysiological properties of
      cultured cerebellar Purkinje neurons.
AB  - The chemokine CCL2 is produced at high levels in the central nervous system (CNS)
      during infection, injury, neuroinflammation and other pathological conditions.
      Cells of the CNS including neurons and glia express receptors for CCL2 and these
      receptors may contribute to a signaling system through which pathologic
      conditions in the CNS are communicated. However, our understanding of the
      consequences of activation of chemokine signaling in the CNS is limited,
      especially for neurons. In many cell types, chemokine signaling alters
      intracellular Ca(2+) dynamics. Therefore, we investigated the potential
      involvement of this mechanism in neuronal signaling activated by CCL2. In
      addition, we examined the effects of CCL2 on neuronal excitability. The studies
      focused on the rat cerebellar Purkinje neuron, an identified CNS neuronal type
      reported to express both CCL2 and its receptor, CCR2. Immunohistochemical studies
      of Purkinje neurons in situ confirmed that they express CCR2 and CCL2. The effect
      of exogenous application on Purkinje neurons was studied in a cerebellar culture
      preparation. CCL2 was tested by micropressure or bath application, at high
      concentrations (13-100 nm) to simulate conditions during a pathologic state.
      Results show that Purkinje neurons express receptors for CCL2 and that activation
      of these receptors alters several neuronal properties. CCL2 increased resting
      Ca(2+) levels, enhanced the Ca(2+) response evoked by activation of metabotropic
      glutamate receptor 1 and depressed action potential generation in the cultured
      Purkinje neurons. Passive membrane properties were unaltered. These modulatory
      effects of CCL2 on neuronal properties are likely to contribute to the altered
      CNS function associated with CNS disease and injury.

PMID- 15978007
TI  - The opioid fentanyl affects light input, electrical activity and Per gene
      expression in the hamster suprachiasmatic nuclei.
AB  - The suprachiasmatic nuclei (SCN) contain a major circadian pacemaker, which is
      regulated by photic and nonphotic stimuli. Although enkephalins are present in
      the SCN, their role in phase regulation of the pacemaker is largely unknown. The
      opioid agonist fentanyl, a homologue of morphine, is an addictive drug that
      induces phase shifts of circadian rhythms in hamsters. We observed that these
      phase shifts are blocked by naloxone, which is a critical test for true opioid
      receptor involvement, and conclude that opioid receptors are the sole mediators
      of the actions of fentanyl on the circadian timing system. A strong interaction
      between opioids and light input was shown by the ability of fentanyl and light to
      completely block each other's phase shifts of behavioural activity rhythms.
      Neuronal ensemble recordings in vitro provide first evidence that SCN cells show
      direct responses to fentanyl and react with a suppression of firing rate.
      Moreover, we show that fentanyl induces a strong attenuation of light-induced
      Syrian hamster Period 1 (shPer1) gene expression during the night. During the
      subjective day, we found no evidence for a role of shPer1 in mediation of
      fentanyl-induced phase shifts. Based on the present results, however, we cannot
      exclude the involvement of shPer2. Our data indicate that opioids can strongly
      modify the photic responsiveness of the circadian pacemaker and may do so via
      direct effects on SCN electrical activity and regulation of Per genes. This
      suggests that the pathways regulating addictive behaviour and the circadian clock
      intersect.

PMID- 15978008
TI  - Photoperiod regulates multiple gene expression in the suprachiasmatic nuclei and
      pars tuberalis of the Siberian hamster (Phodopus sungorus).
AB  - Photoperiod regulates the seasonal physiology of many mammals living in temperate
      latitudes. Photoperiodic information is decoded by the master circadian clock in
      the suprachiasmatic nuclei (SCN) of the hypothalamus and then transduced via
      pineal melatonin secretion. This neurochemical signal is interpreted by tissues
      expressing melatonin receptors (e.g. the pituitary pars tuberalis, PT) to drive
      physiological changes. In this study we analysed the photoperiodic regulation of
      the circadian clockwork in the SCN and PT of the Siberian hamster. Female
      hamsters were exposed to either long or short photoperiod for 8 weeks and sampled
      at 2-h intervals across the 24-h cycle. In the SCN, rhythmic expression of the
      clock genes Per1, Per2, Cry1, Rev-erbalpha, and the clock-controlled genes
      arginine vasopressin (AVP) and d-element binding protein (DBP) was modulated by
      photoperiod. All of these E-box-containing genes tracked dawn, with earlier peak
      mRNA expression in long, compared to short, photoperiod. This response occurred
      irrespective of the presence of additional regulatory cis-elements, suggesting
      photoperiodic regulation of SCN gene expression through a common E-box-related
      mechanism. In long photoperiod, expression of Cry1 and Per1 in the PT tracked the
      onset and offset of melatonin secretion, respectively. However, whereas Cry1
      tracked melatonin onset in short period, Per1 expression was not detectably
      rhythmic. We therefore propose that, in the SCN, photoperiodic regulation of
      clock gene expression primarily occurs via E-boxes, whereas melatonin-driven
      signal transduction drives the phasing of a subset of clock genes in the PT,
      independently of the E-box.

PMID- 15978009
TI  - Differential modulation of anterior cingulate cortical activity by afferents from
      ventral tegmental area and mediodorsal thalamus.
AB  - A distinct increase in cell firing activity is reported in prefrontal cortex
      during working memory tasks. The afferents that modulate this activity are not
      yet identified. Using in vivo intracellular recording and labelling of prefrontal
      cortical pyramidal neurons in anaesthetized rats, we systematically evaluated the
      influences of afferent projections arising from the ventral tegmental area (VTA)
      and mediodorsal thalamus (MD) by phasic electrical stimulation with a range of
      stimulus frequencies. Both VTA- and MD-responsive pyramidal neurons exhibited
      extensive intracortical axon arborization. Neither single shocks to the VTA at
      0.2 Hz, nor low frequency trains of stimuli at 1-4 Hz (< 5 Hz) interrupted the
      periodicity of membrane bistability in bistable pyramidal neurons. However, high
      frequency VTA-train stimulation (10-50 Hz) interrupted the bistability, and
      produced sustained membrane depolarizations accompanied by intense tonic firing
      in a frequency-dependent manner. Electrical stimulation of MD (10-50 Hz) did not
      produce sustained activity in the same PFC neurons. Thus, the sustained activity
      induced by high-frequency VTA trains is input selective. This effect of VTA-train
      stimulation was attenuated by systemic injection of the D1 receptor antagonist,
      SCH 23390, and blocked by acute dopamine (DA) depletion produced via alpha-methyl
      para-tyrosine pre-treatment, suggesting that sustained cortical activity is
      mediated by DA. Chemical stimulation of VTA via intra-VTA infusion of NMDA
      induced sustained activity similar to VTA-train stimulation. Thus, while both VTA
      and MD-responsive pyramidal neurons exhibited extensive intracortical axon
      arborization, VTA synapses (as opposed to MD synapses) may be critically
      positioned in the dendritic arborizations of anterior cingulate cortical
      pyramidal neurons, which may allow their modulation of sustained activity in
      prefrontal bistable neurons.

PMID- 15978010
TI  - Dopaminergic regulation of orexin neurons.
AB  - Orexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical
      area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to
      corticolimbic sites and subserve psychostimulant-induced locomotor activity.
      However, it is not known whether dopamine neurons in turn regulate the activity
      of orexin cells. We examined the ability of dopamine agonists to activate orexin
      neurons in the rat, as reflected by induction of Fos. The mixed dopamine agonist
      apomorphine increased Fos expression in orexin cells, with a greater effect on
      orexin neurons located medial to the fornix. Both the selective D1-like agonist,
      A-77636, and the D2-like agonist, quinpirole, also induced Fos in orexin cells,
      suggesting that stimulation of either receptor subtype is sufficient to activate
      orexin neurons. Consistent with this finding, combined SCH 23390 (D1 antagonist)
      haloperidol (D2 antagonist) pretreatment blocked apomorphine-induced activation
      of medial as well as lateral orexin neurons; in contrast, pretreatment with
      either the D1-like or D2-like antagonists alone did not attenuate apomorphine
      induced activation of medial orexin cells. In situ hybridization histochemistry
      revealed that LH/PFA cells rarely express mRNAs encoding dopamine receptors,
      suggesting that orexin cells are transsynaptically activated by apomorphine. We
      therefore lesioned the nucleus accumbens, a site known to regulate orexin cells,
      but this treatment did not alter apomorphine-elicited activation of medial or
      lateral orexin neurons. Interestingly, apomorphine failed to activate orexin
      cells in isoflurane-anaesthetized animals. These data suggest that apomorphine
      induced arousal but not accumbens-mediated hyperactivity is required for dopamine
      to transsynaptically activate orexin neurons.

PMID- 15978011
TI  - Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor
      gamma2 F77I point mutation.
AB  - Zolpidem is a hypnotic benzodiazepine site agonist with some gamma-aminobutyric
      acid (GABA)(A) receptor subtype selectivity. Here, we have tested the effects of
      zolpidem on the hippocampus of gamma2 subunit (gamma2F77I) point mutant mice.
      Analysis of forebrain GABA(A) receptor expression with immunocytochemistry,
      quantitative [(3)H]muscimol and [(35)S] t-butylbicyclophosphorothionate (TBPS)
      autoradiography, membrane binding with [(3)H]flunitrazepam and [(3)H]muscimol,
      and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters
      did not reveal any differences between homozygous gamma2I77/I77 and gamma2F77/F77
      mice. However, quantitative immunoblot analysis of gamma2I77/I77 hippocampi
      showed some increased levels of gamma2, alpha1, alpha4 and delta subunits,
      suggesting that differences between strains may exist in unassembled subunit
      levels, but not in assembled receptors. Zolpidem (1 microm) enhanced the decay of
      mIPSCs in CA1 pyramidal cells of control (C57BL/6J, gamma2F77/F77) mice by
      approximately 60%, and peak amplitude by approximately 20% at 33-34 degrees C in
      vitro. The actions of zolpidem (100 nm or 1 microm) were substantially reduced in
      gamma2I77/I77 mice, although residual effects included a 9% increase in decay and
      5% decrease in peak amplitude. Similar results were observed in CA1 stratum
      oriens/alveus interneurons. At network level, the effect of zolpidem (10 microm)
      on carbachol-induced oscillations in the CA3 area of gamma2I77/I77 mice was
      significantly different compared with controls. Thus, the gamma2F77I point
      mutation virtually abolished the actions of zolpidem on GABA(A) receptors in the
      hippocampus. However, some residual effects of zolpidem may involve receptors
      that do not contain the gamma2 subunit.

PMID- 15978012
TI  - Sexually dimorphic expression of Usp9x is related to sex chromosome complement in
      adult mouse brain.
AB  - We found the expression of Usp9x, an X-linked gene which encodes a ubiquitin
      protease implicated in synaptic development, to be significantly higher in the
      adult female mouse brains than in male brains. The sex difference in expression
      of Usp9x was localized to specific brain regions such as neocortex. Furthermore,
      in gonadally intact and gonadectomized mice, XX mice expressed Usp9x mRNA and
      protein more highly than XY mice irrespective of their gonadal type. No sex
      difference was found in the neonatal brain or peripheral tissues such as the
      adult kidney. This finding implies that the difference in sex chromosome
      complement between XY males and XX females could potentially contribute to sexual
      differentiation of brain structure and function. The relation of genomic dose and
      Usp9x expression could help explain the neural and behavioural phenotype of women
      with XO Turner syndrome.

PMID- 15978013
TI  - Sexual dimorphisms in the effect of low-level p25 expression on synaptic
      plasticity and memory.
AB  - p25, a degradation product of p35, has been reported to accumulate in the
      forebrain of patients with Alzheimer's disease. p25 as well as p35 are activators
      of cyclin-dependent kinase 5 (Cdk5) although p25/Cdk5 and p35/Cdk5 complexes have
      distinct properties. Several mouse models with high levels of p25 expression
      exhibit signs of neurodegeneration. On the contrary, we have shown that low
      levels of p25 expression do not cause neurodegeneration and are even beneficial
      for particular types of learning and memory [Angelo et al., (2003) Eur J.
      Neurosci., 18, 423-431]. Here, we have studied the influence of low-level p25
      expression in hippocampal synaptic plasticity and in learning and memory for each
      sex separately in two different genetic backgrounds (129B6F1 and C57BL/6).
      Surprisingly, we found that low-level p25 expression had different consequences
      in male and female mutants. In the two genetic backgrounds LTP induced by a
      strong stimulation of the Schaffer's collaterals (four trains, 1-s duration, 5
      min interval) was severely impaired in male, but not in female, p25 mutants.
      Furthermore, in the two genetic backgrounds spatial learning in the Morris water
      maze was faster in female p25 mutants than in male transgenic mice. These results
      suggest that, in women, the production of p25 in Alzheimer's disease could be a
      compensation for some early learning and memory deficits.

PMID- 15978014
TI  - GABAB and CB1 cannabinoid receptor expression identifies two types of septal
      cholinergic neurons.
AB  - Septohippocampal cholinergic neurons play key roles in learning and memory
      processes, and in the generation of hippocampal theta rhythm. The range of
      receptors for endogenous modulators expressed on these neurons is unclear. Here
      we describe GABA(B) 1a/b receptor (GABA(B)R) and type 1 cannabinoid receptor
      (CB(1)R) expression in rat septal cholinergic [i.e. choline acetyltransferase
      (ChAT)-positive] cells. Using double immunofluorescent staining, we found that
      almost two-thirds of the cholinergic cells in the rat medial septum were GABA(B)R
      positive, and that these cells had significantly larger somata than did GABA(B)R
      negative cholinergic neurons. We detected CB(1)R labelling in somata after axonal
      protein transport was blocked by colchicine. In these animals about one-third of
      the cholinergic cells were CB(1)R positive. These cells again had larger somata
      than CB(1)R-negative cholinergic neurons. The analyses confirmed that the size of
      GABA(B)R-positive and CB(1)R-positive cholinergic cells were alike, and all
      CB(1)R-positive cholinergic cells were GABA(B)R positive as well. CB(1)R-positive
      cells were invariably ChAT positive. All retrogradely labelled septohippocampal
      cholinergic cells were positive for GABA(B)R and at least half of them also for
      CB(1)R. These data shed light on the existence of at least two cholinergic cell
      types in the medial septum: one expresses GABA(B)R and CB(1)R, has large somata
      and projects to the hippocampus, whereas the other is negative for GABA(B)R and
      CB(1)R and has smaller somata. The results also suggest that cholinergic
      transmission in the hippocampus is fine-tuned by endocannabinoid signalling.

PMID- 15978015
TI  - The dopamine-synthesizing cells in the swimming larva of the tunicate Ciona
      intestinalis are located only in the hypothalamus-related domain of the sensory
      vesicle.
AB  - Dopamine is a major neuromodulator synthesized by numerous cell populations in
      the vertebrate forebrain and midbrain. Owing to the simple organization of its
      larval nervous system, ascidian tunicates provide a useful model to investigate
      the anatomy, neurogenesis and differentiation of the dopaminergic neural network
      underlying the stereotypical swimming behaviour of its chordate-type larva. This
      study provides a high-resolution cellular analysis of tyrosine hydroxylase (TH)
      positive and dopamine-positive cells in Ciona intestinalis embryos and larvae.
      Dopamine cells are present only in the sensory vesicle of the Ciona larval brain,
      which may be an ancestral chordate feature. The dopamine-positive cells of the
      ascidian sensory vesicle are located in the expression domain of homologues of
      vertebrate hypothalamic markers. We show here that the larval coronet cells also
      arise from this domain. As a similar association between coronet cells and the
      hypothalamus was reported in bony and cartilaginous fishes, we propose that part
      of the ascidian ventral sensory vesicle is the remnant of a proto-hypothalamus
      that may have been present in the chordate ancestor. As dopaminergic cells are
      specified in the hypothalamus in all vertebrates, we suggest that the mechanisms
      of dopamine cell specification are conserved in the hypothalamus of Ciona and
      vertebrates. To test this hypothesis, we have identified new candidate regulators
      of dopaminergic specification in Ciona based on their expression patterns, which
      can now be compared with those in vertebrates.

PMID- 15978016
TI  - Occipital (V6) and parietal (V6A) areas in the anterior wall of the parieto
      occipital sulcus of the macaque: a cytoarchitectonic study.
AB  - The anterior wall of the parieto-occipital sulcus (POs) of the macaque monkey,
      classically considered as part of Brodmann's area 19, contains two functionally
      distinct areas: a ventral, purely visual area, V6, and a dorsal area, V6A,
      containing visual neurons and neurons related to the control of arm movements.
      The aim of this study was to establish whether areas V6 and V6A, so far
      identified only on a functional basis, have a cytoarchitectonic counterpart. The
      cytoarchitectonic analysis of 13 hemispheres from ten macaque brains, cut along
      different planes of section, showed that the anterior wall of the POs contains
      three distinct areas. One is located in the ventralmost part of the wall, another
      in the dorsalmost part of the wall, and the third occupies an intermediate
      position. The ventralmost region displays architectonic features typical of the
      occipital cytoarchitectonic domain, whereas the two dorsal areas display
      architectonic features typical of the posterior parietal cortex. Analysis of
      myeloarchitecture and of the distribution of SMI-32 immunoreactivity confirmed
      the cytoarchitectonic parcellation. Correlation of cytoarchitectonic maps with
      functional and hodological data strongly suggests that the ventral region
      corresponds to area V6, whereas the other two regions correspond to different
      subsectors of V6A, here named V6Av and V6Ad, respectively. The present data are
      in line with electrophysiological and hodological data, which suggest that area
      V6 is a classic extrastriate area, whereas V6A is an area of the posterior
      parietal cortex. They also suggest that V6A includes two separate cortical
      subdivisions, a view supported by preliminary functional and hodological data
      that needs further confirmation.

PMID- 15978017
TI  - Neuroanatomical correlates of voluntary inhibition of accommodation/vergence
      under monocular open-loop viewing conditions.
AB  - The purpose of this work is to identify human neural circuits involved in
      inhibition of accommodation/vergence by contrasting the cortical functions
      subservient to negative voluntary accommodation/vergence (NVA) with those evoked
      by active fixation in darkness (FIX). Five subjects with normal corrected acuity
      were studied using positron emission tomography and the HO bolus technique. The
      dominant right eye viewed a laser speckle pattern (633 nm) whose direction and
      velocity of motion were determined by the refractive state of the eye. The
      speckle pattern was presented at a distance of 1.8 m (0.55 D). The non-dominant
      eye was patched. Subjects performed two tasks counterbalanced for order effects:
      (i) attempted fixation on the remembered target in darkness with the dominant eye
      open and 'fixating'; and (ii) voluntary reduction of the laser speckle flow
      during each alternate 20-s epoch when a convex +2.0 D lens was placed in front of
      the right eye causing the speckle pattern to move downwards at 3 degrees /s.
      Comparison of the condition of NVA with the condition of FIX indicated widespread
      occipital activation. Decreases in absolute regional cerebral blood flow occurred
      in the superior parietal cortex (BA 5), frontal cortex (BA 8 and 10) and within
      the postcentral/precentral gyrus (BA 1/2/3/4) bilaterally where deactivation
      clusters eclipsed the presumed neck and shoulder areas. Negative
      accommodation/vergence appears to be driven by a reduction of parasympathetic
      tone, and has the effect of shutting down brain regions known to be involved in
      regulating visual search as well as a centrally controlled eye-head-neck-shoulder
      motor programme responsible for posturing gaze.

PMID- 15978018
TI  - The reinforcing effects of chronic D-amphetamine and morphine are impaired in a
      line of memory-deficient mice overexpressing calcineurin.
AB  - It has recently emerged that there is a commonality in the molecular mechanisms
      underlying long-term neuronal changes in drug addiction and those mediating
      synaptic plasticity associated with learning and memory. In the hippocampus, the
      calcium-calmodulin-dependent protein phosphatase calcineurin plays a pivotal role
      in the molecular mechanisms that underlie learning and memory functions.
      Transgenic mice that express an active form of calcineurin specifically in
      forebrain structures have previously been shown to have a deficit in the
      transition from short- to long-term memory. Here, we investigated the involvement
      of calcineurin in the motivational effects of amphetamine and morphine using this
      line of transgenic mice (CN98). Our results showed that amphetamine and morphine
      did not induce conditioned place preference in calcineurin-mutant mice, whereas
      food remained an efficient reinforcer. In addition, behavioural sensitization to
      these two drugs, as measured by horizontal locomotion, was disturbed in the
      transgenic mice. In contrast, neither the horizontal locomotion in response to
      acute D-amphetamine or morphine nor the somatic signs of morphine withdrawal were
      affected in calcineurin mutant mice compared to their wild-type littermates. Our
      data indicate that calcineurin-mediated protein dephosphorylation in the
      hippocampus is involved in the long-term effects of drugs of abuse without
      influencing the motivational response to a natural reward or the physical
      component of opioid withdrawal. The present results emphasize the essential role
      of hippocampal-dependent learning and memory in the development of drug
      addiction.

PMID- 15978019
TI  - A neural signature of colour and luminance correspondence in bistable apparent
      motion.
AB  - The 'correspondence problem' refers to the ambiguity of apparent motion (AM)
      paths if several similar objects are displaced across successive displays. We
      investigated the effect of intrinsic object properties such as colour and
      luminance on AM paths, and used functional magnetic resonance imaging to localize
      neural correlates of correspondence matching in visual cortical regions. Human
      subjects looked at an AM display where two dots in diagonally opposite corners of
      an implicit rectangle were flashed in alternation with two dots in the other two
      corners, yielding spontaneous alternations between horizontal and vertical AM.
      The dots differed in colour or luminance, or were identical. Neural activity was
      analysed as a function of whether the perceived AM path matched the dots' colour
      or luminance, and was also compared to activity during bistable AM displays
      without correspondence cues. When AM paths matched colour and luminance cues,
      activity in early visual cortex was the same as during perception of uncued
      displays, whereas it was suppressed when perceived AM paths violated colour or
      luminance cues. Colour-sensitive extrastriate cortex (V4 complex) transiently
      activated whenever AM perception switched from a pattern violating colour
      correspondence to one consistent with colour. We propose that the neural
      correlate of correspondence in early visual cortex reflects regulatory mechanisms
      that flexibly gate early visual feature processing in accord with an overriding
      perceptual decision. Conversely, activation of feature-selective extrastriate
      regions depends on the type of cue used for correspondence matching and may
      reflect the salience of percepts that match in colour and motion.

PMID- 15978020
TI  - Lesions to the subthalamic nucleus decrease impulsive choice but impair
      autoshaping in rats: the importance of the basal ganglia in Pavlovian
      conditioning and impulse control.
AB  - Although the subthalamic nucleus (STN) is involved in regulating motor function,
      and inactivation of this structure relieves the motor symptoms in Parkinsonian
      patients, recent data indicate that corticosubthalamic connections are involved
      in both the regulation of attention and the ability to withhold from responding.
      Considerable evidence suggests that the neural circuitry underlying such
      behavioural disinhibition or impulsive action can be at least partially
      dissociated from that implicated in impulsive decision-making and it has been
      suggested that the tendency to choose impulsively is related to the ability to
      form and use Pavlovian associations. To explore these hypotheses further, STN
      lesioned rats were tested on the delay-discounting model of impulsive choice,
      where impulsivity is defined as the selection of a small immediate over a larger
      delayed reward, as well as in a rodent autoshaping paradigm. In contrast to
      previous reports of increased impulsive action, STN lesions decreased impulsive
      choice but dramatically impaired the acquisition of the autoshaping response.
      When the STN was lesioned after the establishment of autoshaping behaviour,
      lesioned subjects were more sensitive to the omission of reward, indicative of a
      reduction in the use of Pavlovian associations to control autoshaping
      performance. These results emphasize the importance of the STN in permitting
      conditioned stimulus-unconditioned stimulus associations to regulate goal
      seeking, a function which may relate to the alterations in impulsive choice
      observed in the delay-discounting task. These data bear a striking similarity to
      those observed after lesions of the orbitofrontal cortex and are suggestive of an
      important role for corticosubthalamic connections in complex cognitive behaviour.

PMID- 15978021
TI  - Microsphere embolism-induced cortical cholinergic deafferentation and impairments
      in attentional performance.
AB  - Ischemic events have been hypothesized to play a critical role on the
      pathogenesis of dementia and the acceleration of cognitive impairments. This
      experiment was designed to determine the consequences of microvascular ischemia
      on the cortical cholinergic input system and associated attention capacities.
      Injections of microspheres ( approximately 50 microm diameter; approximately 5000
      microspheres/100 microL) into the right common carotid artery of rats served as a
      model of microvascular ischemia and resulted in decreases in the density of
      cholinergic fibers in the ipsilateral medial prefrontal cortex and frontoparietal
      areas. Furthermore, dense astrogliosis, indicated by glial fibrillary acidic
      protein (GFAP) immunohistochemistry, was observed in the globus pallidus,
      including the areas of origin of cholinergic projections to the cortex. Fluoro
      Jade B staining indicated that loss of neurons in the cortex was restricted to
      areas of microsphere-induced infarcts. Attentional performance was assessed using
      an operant sustained attention task; performance in this task was previously
      demonstrated to reflect the integrity and activity of the cortical cholinergic
      input system. Embolized animals' performance was characterized by a decrease in
      the animals' ability to detect signals. Their performance in non-signal trials
      remained unaffected. The residual density of cholinergic axons in prefrontal and
      frontoparietal areas correlated with the animals' performance. The present data
      support the hypothesis that microvascular ischemia results in loss of cortical
      cholinergic inputs and impairs associated attentional performance. Microsphere
      embolism represents a useful animal model for studying the role of interactions
      between microvascular disorder and impaired forebrain cholinergic
      neurotransmission in the manifestation of cognitive impairments.

PMID- 15978022
TI  - Attention to pain localization and unpleasantness discriminates the functions of
      the medial and lateral pain systems.
AB  - Functional imaging studies have identified a matrix of structures in the brain
      that respond to noxious stimuli. Within this matrix, a division of function
      between sensory-discriminative and affective responses has so far been
      demonstrated by manipulating either pain intensity or unpleasantness under
      hypnosis in two different normal volunteer groups studied on separate occasions.
      Our study used positron emission tomography (PET) to demonstrate this division of
      function under more natural conditions in a healthy group of volunteers, using a
      CO(2) laser to provide nociceptive stimuli that selectively activate A-delta and
      C-fibres without contamination by touch sensations. We measured the differential
      cerebral responses to noxious and innocuous laser stimuli during conditions of
      selective attention to either the unpleasantness or location of the stimuli.
      Attention to location increased responses in the contralateral (right) primary
      somatosensory and inferior parietal cortices. This result implies that these
      components of the lateral pain system are concerned mainly with the localization
      of pain. In contrast, attention to unpleasantness increased responses in
      bilateral perigenual cingulate and orbitofrontal cortices, contralateral (right)
      amygdala, ipsilateral (left) hypothalamus, posterior insula, M1 and frontal pole.
      These areas comprise key components of the medial pain and neuroendocrine systems
      and the results suggest that they have a role in the affective response to pain.
      Our results indicate the importance of attentional effects on the pattern of
      nociceptive processing in the brain. They also provide the first clear
      demonstration, within a single experiment, of a major division of function within
      the neural pain matrix.

PMID- 15978023
TI  - Learning in realistic networks of spiking neurons and spike-driven plastic
      synapses.
AB  - We have used simulations to study the learning dynamics of an autonomous,
      biologically realistic recurrent network of spiking neurons connected via plastic
      synapses, subjected to a stream of stimulus-delay trials, in which one of a set
      of stimuli is presented followed by a delay. Long-term plasticity, produced by
      the neural activity experienced during training, structures the network and
      endows it with active (working) memory, i.e. enhanced, selective delay activity
      for every stimulus in the training set. Short-term plasticity produces transient
      synaptic depression. Each stimulus used in training excites a selective subset of
      neurons in the network, and stimuli can share neurons (overlapping stimuli). Long
      term plasticity dynamics are driven by presynaptic spikes and coincident
      postsynaptic depolarization; stability is ensured by a refresh mechanism. In the
      absence of stimulation, the acquired synaptic structure persists for a very long
      time. The dependence of long-term plasticity dynamics on the characteristics of
      the stimulus response (average emission rates, time course and synchronization),
      and on the single-cell emission statistics (coefficient of variation) is studied.
      The study clarifies the specific roles of short-term synaptic depression, NMDA
      receptors, stimulus representation overlaps, selective stimulation of inhibition,
      and spike asynchrony during stimulation. Patterns of network spiking activity
      before, during and after training reproduce most of the in vivo physiological
      observations in the literature.

PMID- 15978024
TI  - Knowing good from bad: differential activation of human cortical areas by
      positive and negative outcomes.
AB  - Previous research has identified a component of the event-related brain potential
      (ERP), the feedback-related negativity, that is elicited by feedback stimuli
      associated with unfavourable outcomes. In the present research we used event
      related functional magnetic resonance imaging (fMRI) and electroencephalographic
      (EEG) recordings to test the common hypothesis that this component is generated
      in the caudal anterior cingulate cortex. The EEG results indicated that our
      paradigm, a time estimation task with trial-to-trial performance feedback,
      elicited a large feedback-related negativity (FRN). Nevertheless, the fMRI
      results did not reveal any area in the caudal anterior cingulate cortex that was
      differentially activated by positive and negative performance feedback, casting
      doubt on the notion that the FRN is generated in this brain region. In contrast,
      we found a number of brain areas outside the posterior medial frontal cortex that
      were activated more strongly by positive feedback than by negative feedback.
      These included areas in the rostral anterior cingulate cortex, posterior
      cingulate cortex, right superior frontal gyrus, and striatum. An anatomically
      constrained source model assuming equivalent dipole generators in the rostral
      anterior cingulate, posterior cingulate, and right superior frontal gyrus
      produced a simulated scalp distribution that corresponded closely to the observed
      scalp distribution of the FRN. These results support a new hypothesis regarding
      the neural generators of the FRN, and have important implications for the use of
      this component as an electrophysiological index of performance monitoring and
      reward processing.

PMID- 15978025
TI  - Neuronal mechanisms underlying control of a brain-computer interface.
AB  - Brain-computer interfaces (BCIs) enable humans or animals to communicate or
      control external devices without muscle activity using electric brain signals.
      The BCI used here is based on self-regulation of slow cortical potentials (SCPs),
      a skill that most people and paralyzed patients can acquire with training periods
      of several hours up to months. The neurophysiological mechanisms and anatomical
      sources of SCPs and other event-related brain potentials have been described but
      the neural mechanisms underlying the self-regulation skill for the use of a BCI
      are unknown. To uncover the relevant areas of brain activation during regulation
      of SCPs, the BCI was combined with functional magnetic resonance imaging. The
      electroencephalogram was recorded inside the magnetic resonance imaging scanner
      in 12 healthy participants who learned to regulate their SCP with feedback and
      reinforcement. The results demonstrate activation of specific brain areas during
      execution of the brain regulation skill allowing a person to activate an external
      device; a successful positive SCP shift compared with a negative shift was
      closely related to an increase of the blood oxygen level-dependent response in
      the basal ganglia. Successful negativity was related to an increased blood oxygen
      level-dependent response in the thalamus compared with successful positivity.
      These results may indicate learned regulation of a cortico-striatal-thalamic loop
      modulating local excitation thresholds of cortical assemblies. The data support
      the assumption that human subjects learn the regulation of cortical excitation
      thresholds of large neuronal assemblies as a prerequisite for direct brain
      communication using an SCP-driven BCI. This skill depends critically on an intact
      and flexible interaction between the cortico-basal ganglia-thalamic circuits.

PMID- 15978026
TI  - Functional properties of neuronal nicotinic acetylcholine receptors in the chick
      retina during development.
AB  - Acetylcholine (ACh) has been recognized for a long time as a major
      neurotransmitter in the retina, however, little is known about the contribution
      of acetylcholine receptors in synaptic processing. Moreover, even less
      information is available concerning their role during development. To address
      this question further, we examined the physiological and pharmacological
      properties of neuronal nicotinic acetylcholine receptors (nAChRs) in retinal
      ganglion cells from embryonic (E) 12-18-day-old Leghorn chicks. Patch-clamp
      recordings in whole-cell configuration revealed that at E12 approximately 21% of
      the ganglion cells responded to acetylcholine pulses with inward currents. The
      number of responsive cells progressively increased to 57% at E15 to reach up to
      15 positive cells out of 15 cells tested at E18. Acetylcholine-evoked responses
      could be subdivided, according to their time course, into fast and slowly
      desensitizing. Taking advantage of the selectivity of the frog toxin epibatidine
      (Epi), that preferentially activates heteromeric neuronal nicotinic acetylcholine
      receptors, we compared the currents evoked by this toxin vs. the effects of
      acetylcholine. A further characterization of the receptor diversity during
      development was to assess their sensitivity to the alpha-conotoxin MII (alpha-CTX
      MII), which has been shown to preferentially block alpha6- and alpha3beta2
      containing receptors. These data demonstrate that ganglion cells of the chick
      retina express multiple receptor subtypes that progressively develop as a
      function of retina maturation.

PMID- 15978027
TI  - Reduced infarct volume and differential effects on glial cell activation after
      hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia.
AB  - Permanent middle cerebral artery occlusion (MCAO) causes neurodegeneration and a
      robust activation of glial cells primarily in sensorimotor brain regions of rats.
      It has been shown that hyperbaric oxygen (HBO) increases oxygen supply to
      ischaemic areas and reduces neuronal cell loss. The effects of HBO treatment on
      microgliosis and astrogliosis in permanent cerebral ischaemia have not been
      addressed so far, but might be critical for neurodegeneration and
      neuroprotection, respectively. Therefore, we used spontaneously hypertensive rats
      with permanent MCAO to investigate the time window to start HBO and to compare
      the effects of different HBO treatment frequencies on infarct volume and on
      differences with regard to microgliosis and astrogliosis. Seven days after MCAO
      the infarct volume was calculated from Nissl-stained brain sections by image
      analysis. HBO significantly decreased the infarct volume when used as early as
      15, 90 or 180 min post-MCAO by 24%, 16% and 13%, respectively, in the single
      treatment group. Repetitive HBO treatment (first HBO session 90 min after MCAO)
      was not effective. Microglial cells and astrocytes were detected by cytochemical
      fluorescent labelling and confocal laser scanning microscopy. In the single
      treatment group we observed significantly higher astrocyte immunoreactivity but
      decreased microglial density in the peri-infarct region. These effects of HBO
      treatment on glial cells were not present in rats where HBO did not reduce the
      infarct volume (360 min after MCAO). Our data indicate that HBO-induced
      suppression of microgliosis and aggravated response of astrocytes might
      contribute to the reported beneficial effects of early HBO treatment in cerebral
      ischaemia.

PMID- 15978028
TI  - What is said or how it is said makes a difference: role of the right fronto
      parietal operculum in emotional prosody as revealed by repetitive TMS.
AB  - Emotional signals in spoken language can be conveyed by semantic as well as
      prosodic cues. We investigated the role of the fronto-parietal operculum, a
      somatosensory area where the lips, tongue and jaw are represented, in the right
      hemisphere to detection of emotion in prosody vs. semantics. A total of 14
      healthy volunteers participated in the present experiment, which involved
      transcranial magnetic stimulation (TMS) in combination with frameless stereotaxy.
      As predicted, compared with sham stimulation, TMS over the right fronto-parietal
      operculum differentially affected the reaction times for detection of emotional
      prosody vs. emotional semantics, showing that there is a dissociation at a
      neuroanatomical level. Detection of withdrawal emotions (fear and sadness) in
      prosody was delayed significantly by TMS. No effects of TMS were observed for
      approach emotions (happiness and anger). We propose that the right fronto
      parietal operculum is not globally involved in emotion evaluation, but sensitive
      to specific forms of emotional discrimination and emotion types.

PMID- 15978029
TI  - A kind of auditory 'primitive intelligence' already present at birth.
AB  - 'Primitive intelligence' in audition refers to the capacity of the auditory
      system to adaptatively model the acoustic regularity and react
      neurophysiologically to violations of such regularity, thus supporting the
      ability to predict future auditory events. In the present study, event-related
      brain potentials to pairs of tones were recorded in 11 human newborns to
      determine the infants' ability to extract an abstract acoustic rule, the
      direction of a frequency change. Most of the pairs (standard, P = 0.875) were of
      ascending frequency (i.e. the second tone higher than the first), while the
      remaining pairs (deviant, P = 0.125) were of descending frequency (the second
      tone being lower). Their frequencies varied among seven levels to prevent
      discrimination between standard and deviant pairs on the basis of absolute
      frequencies. We found that event-related brain potentials to deviant pairs
      differed in amplitude from those to standard pairs at 50-450 ms from the onset of
      the second tone of a pair, indicating the infants' ability to represent the
      abstract rule. This finding suggests the early ontogenetic origin of 'primitive
      intelligence' in audition that eventually may form a prerequisite for later
      language acquisition.

PMID- 15978030
TI  - Histone H2A phosphorylation in DNA double-strand break repair.
AB  - DNA repair must take place within the context of chromatin, and it is therefore
      not surprising that many aspects of both chromatin components and proteins that
      modify chromatin have been implicated in this process. One of the best
      characterized chromatin modification events in DNA-damage responses is the
      phosphorylation of the SQ motif found in histone H2A or the H2AX histone variant
      in higher eukaryotes. This modification is an early response to the induction of
      DNA damage, and occurs in a wide range of eukaryotic organisms, suggesting an
      important conserved function. One function that histone modifications can have is
      to provide a unique binding site for interacting factors. Here, we review the
      proteins and protein complexes that have been identified as H2AS129ph (budding
      yeast) or H2AXS139ph (human) binding partners and discuss the implications of
      these interactions.

PMID- 15978031
TI  - Diego and friends play again.
AB  - The formation of properly differentiated organs often requires the planar
      coordination of cell polarization within the tissues. Such planar cell
      polarization (PCP) events are best studied in Drosophila, where many of the key
      players, known as PCP genes, have already been identified. Genetic analysis of
      the PCP genes suggests that the establishment of polarity consists of three major
      steps. The first step involves the generation of a global polarity cue; this in
      turn promotes the second step, the redistribution of the core PCP proteins,
      leading to the formation of asymmetrically localized signaling centers. During
      the third step, these complexes control tissue-specific cellular responses
      through the activation of cell type specific effector genes. Here we discuss some
      of the most recent advances that have provided valuable new insight into each of
      the three major steps of planar cell polarization.

PMID- 15978032
TI  - Long-distance interactions between enhancers and promoters.
AB  - Abdominal-B (Abd-B) is a complex homeotic gene with a difficult task: one
      transcript determines the identity of four different abdominal segments
      throughout development in Drosophila. Although an increasing amount of
      information is available about the structure and the functioning of the
      regulatory regions that determine the expression pattern of Abd-B, it is still
      not clear how these regulatory regions can contact the distantly located (several
      tens of kilobases away) promoter in the nucleus, what mechanism restricts
      promiscuous enhancers to this specific interaction, and how different regulatory
      regions replace one another at the same promoter in subsequent abdominal
      segments. Moreover, several of these regulatory regions have to act over
      chromatin domain boundaries and extensive inactive chromatin domains, similarly
      to the situation found in the chicken beta-globin cluster. In this minireview we
      survey mechanisms and factors that may be involved in mediating specific
      interactions between the Abd-B promoter and its regulatory regions.

PMID- 15978033
TI  - Quantitative estimation of channeling from early glycolytic intermediates to CO
      in intact Escherichia coli.
AB  - A pathway intermediate is said to be 'channeled' when an intermediate just made
      in a pathway has a higher probability of being a substrate for the next pathway
      enzyme compared with a molecule of the same species from the aqueous cytoplasm.
      Channeling is an important phenomenon because it might play a significant role in
      the regulation of metabolism. Whereas the usual mechanism proposed for channeling
      is the (often) transient interaction of sequential pathway enzymes, many of the
      supporting data come from results with pure enzymes and dilute cell extracts.
      Even when isotope dilution techniques have utilized whole-cell systems, most
      often only a qualitative assessment of channeling has been reported. Here we
      develop a method for making a quantitative calculation of the fraction channeled
      in glycolysis from in vivo isotope dilution experiments. We show that fructose
      1,6-bisphosphate, in whole cells of Escherichia coli, was strongly channeled all
      the way to CO2, whereas fructose-6-phosphate was not. Because the signature of
      channeling is lost if any downstream intermediate prior to CO2 equilibrates with
      molecules in the aqueous cytosol, it was not possible to evaluate whether glucose
      6-phosphate was channeled in its transformation to fructose-6-phosphate. The data
      also suggest that, in addition to pathway enzymes being associated with one
      another, some are free in the aqueous cytosol. How sensitive the degree of
      channeling is to growth or experimental conditions remains to be determined.

PMID- 15978034
TI  - Two types of replication protein A in seed plants.
AB  - Replication protein A (RPA), a heterotrimeric protein composed of 70, 32 and 14
      kDa subunits, has been shown to be essential for DNA replication, repair,
      recombination, and transcription. Previously, we found that, in two seed plants,
      rice and Arabidopsis, there are two different types of RPA70-kDa subunit.
      Substantial biochemical and genetic characterization of these two subunits,
      termed OsRPA70a and OsRPA70b or AtRPA70a and AtRPA70b, respectively, is described
      in this report. Inactivation of AtRPA70a by transfer DNA insertion or RNA
      interference is lethal, so the complex containing RPA70a may be essential for DNA
      replication. Transfer DNA insertion and RNAi lines for AtRPA70b are
      morphologically normal, albeit hypersensitive to certain mutagens, such as UV-B
      and methyl methanesulfonate, suggesting that RPA70b functions mostly in DNA
      repair. In two-hybrid, pull-down and coexpression analysis, OsRPA70b was found to
      interact more selectively than OsRPA70a with OsRPA32. The data suggest that two
      different types of RPA heterotrimer are present in seed plants, and that there
      may be additional 32 and 14-kDa subunit homologs that interact with OsRPA70a.
      Each of the two probable plant RPA complexes may have different roles in DNA
      metabolism.

PMID- 15978035
TI  - Characterization of electrogenic bromosulfophthalein transport in carnation petal
      microsomes and its inhibition by antibodies against bilitranslocase.
AB  - Bilitranslocase is a rat liver plasma membrane carrier, displaying a high
      affinity binding site for bilirubin. It is competitively inhibited by grape
      anthocyanins, including aglycones and their mono- and di-glycosylated
      derivatives. In plant cells, anthocyanins are synthesized in the cytoplasm and
      then translocated into the central vacuole, by mechanisms yet to be fully
      characterized. The aim of this work was to determine whether a homologue of rat
      liver bilitranslocase is expressed in carnation petals, where it might play a
      role in the membrane transport of anthocyanins. The bromosulfophthalein-based
      assay of rat liver bilitranslocase transport activity was implemented in
      subcellular membrane fractions, leading to the identification of a
      bromosulfophthalein carrier (K(M) = 5.3 microm), which is competitively inhibited
      by cyanidine 3-glucoside (Ki = 51.6 microm) and mainly noncompetitively by
      cyanidin (Ki = 88.3 microm). Two antisequence antibodies against bilitranslocase
      inhibited this carrier. In analogy to liver bilitranslocase, one antibody
      identified a bilirubin-binding site (Kd = 1.7 nm) in the carnation carrier. The
      other antibody identified a high-affinity binding site for cyanidine 3-glucoside
      (Kd = 1.7 microm) on the carnation carrier only, and a high-affinity bilirubin
      binding site (Kd = 0.33 nm) on the liver carrier only. Immunoblots showed a
      putative homologue of rat liver bilitranslocase in both plasma membrane and
      tonoplast fractions, isolated from carnation petals. Furthermore, only epidermal
      cells were immunolabeled in petal sections examined by microscopy. In conclusion,
      carnation petals express a homologue of rat liver bilitranslocase, with a
      putative function in the membrane transport of secondary metabolites.

PMID- 15978036
TI  - A novel carbonic anhydrase from the giant clam Tridacna gigas contains two
      carbonic anhydrase domains.
AB  - This report describes the presence of a unique dual domain carbonic anhydrase
      (CA) in the giant clam, Tridacna gigas. CA plays an important role in the
      movement of inorganic carbon (Ci) from the surrounding seawater to the symbiotic
      algae that are found within the clam's tissue. One of these isoforms is a
      glycoprotein which is significantly larger (70 kDa) than any previously reported
      from animals (generally between 28 and 52 kDa). This alpha-family CA contains two
      complete carbonic anhydrase domains within the one protein, accounting for its
      large size; dual domain CAs have previously only been reported from two algal
      species. The protein contains a leader sequence, an N-terminal CA domain and a C
      terminal CA domain. The two CA domains have relatively little identity at the
      amino acid level (29%). The genomic sequence spans in excess of 17 kb and
      contains at least 12 introns and 13 exons. A number of these introns are in
      positions that are only found in the membrane attached/secreted CAs. This fact,
      along with phylogenetic analysis, suggests that this protein represents the
      second example of a membrane attached invertebrate CA and it contains a dual
      domain structure unique amongst all animal CAs characterized to date.

PMID- 15978038
TI  - Role of the surface charges D72 and K8 in the function and structural stability
      of the cytochrome c from Nostoc sp. PCC 7119.
AB  - We investigated the role of electrostatic charges at positions D72 and K8 in the
      function and structural stability of cytochrome c6 from Nostoc sp. PCC 7119 (cyt
      c6). A series of mutant forms was generated to span the possible combinations of
      charge neutralization (by mutation to alanine) and charge inversion (by mutation
      to lysine and aspartate, respectively) in these positions. All forms of cyt c6
      were functionally characterized by laser flash absorption spectroscopy, and their
      stability was probed by urea-induced folding equilibrium relaxation experiments
      and differential scanning calorimetry. Neutralization or inversion of the
      positive charge at position K8 reduced the efficiency of electron transfer to
      photosystem I. This effect could not be reversed by compensating for the change
      in global charge that had been introduced by the mutation, indicating a specific
      role for K8 in the formation of the electron transfer complex between cyt c6 and
      photosystem I. Replacement of D72 by asparagine or lysine increased the
      efficiency of electron transfer to photosystem I, but destabilized the protein.
      D72 apparently participates in electrostatic interactions that stabilize the
      structure of cyt c6. The destabilizing effect was reduced when aspartate was
      replaced by the small amino acid alanine. Complementing the mutation D72A with a
      charge neutralization or inversion at position K8 led to mutant forms of cyt c6
      that were more stable than the wild-type under all tested conditions.

PMID- 15978037
TI  - Redox-regulated affinity of the third PDZ domain in the phosphotyrosine
      phosphatase PTP-BL for cysteine-containing target peptides.
AB  - PDZ domains are protein-protein interaction modules that are crucial for the
      assembly of structural and signalling complexes. They specifically bind to short
      C-terminal peptides and occasionally to internal sequences that structurally
      resemble such peptide termini. The binding of PDZ domains is dominated by the
      residues at the P(0) and P(-2) position within these C-terminal targets, but
      other residues are also important in determining specificity. In this study, we
      analysed the binding specificity of the third PDZ domain of protein tyrosine
      phosphatase BAS-like (PTP-BL) using a C-terminal combinatorial peptide phage
      library. Binding of PDZ3 to C-termini is preferentially governed by two cysteine
      residues at the P(-1) and P(-4) position and a valine residue at the P(0)
      position. Interestingly, we found that this binding is lost upon addition of the
      reducing agent dithiothrietol, indicating that the interaction is disulfide
      bridge-dependent. Site-directed mutagenesis of the single cysteine residue in
      PDZ3 revealed that this bridge formation does not occur intermolecularly, between
      peptide and PDZ3 domain, but rather is intramolecular. These data point to a
      preference of PTP-BL PDZ3 for cyclic C-terminal targets, which may suggest a
      redox state-sensing role at the cell cortex.

PMID- 15978039
TI  - Detection of nucleolar organizer and mitochondrial DNA insertion regions based on
      the isochore map of Arabidopsis thaliana.
AB  - Eukaryotic genomes are composed of isochores, i.e. long sequences relatively
      homogeneous in GC content. In this paper, the isochore structure of Arabidopsis
      thaliana genome has been studied using a windowless technique based on the Z
      curve method and intuitive curves are drawn for all the five chromosomes. Using
      these curves, we can calculate the GC content at any resolution, even at the base
      level. It is observed that all the five chromosomes are composed of several GC
      rich and AT-rich regions alternatively. Usually, these regions, named 'isochore
      like regions', have large fluctuations in the GC content. Five isochores with
      little fluctuations are also observed. Detailed analyses have been performed for
      these isochores. A GC-rich 'isochore-like region' and a GC-isochore in chromosome
      II and IV, respectively, are the nucleolar organizer regions (NORs), and genes
      located in the two regions prefer to use GC-ending codons. Another GC-isochore
      located in chromosome II is a mitochondrial DNA insertion region, the position
      and size of this region is precisely predicted by the current method. The amino
      acid usage and codon preference of genes in this organellar-to-nuclear transfer
      region show significant difference from other regions. Moreover, the centromeres
      are located in GC-rich 'isochore-like regions' in all the five chromosomes. The
      current method can provide a useful tool for analyzing whole genomic sequences of
      eukaryotes.

PMID- 15978040
TI  - Identification of ATP-NADH kinase isozymes and their contribution to supply of
      NADP(H) in Saccharomyces cerevisiae.
AB  - ATP-NAD kinase phosphorylates NAD to produce NADP by using ATP, whereas ATP-NADH
      kinase phosphorylates both NAD and NADH. Three NAD kinase homologues, namely, ATP
      NAD kinase (Utr1p), ATP-NADH kinase (Pos5p) and function-unknown Yel041wp
      (Yef1p), are found in the yeast Saccharomyces cerevisiae. In this study, Yef1p
      was identified as an ATP-NADH kinase. The ATP-NADH kinase activity of Utr1p was
      also confirmed. Thus, the three NAD kinase homologues were biochemically
      identified as ATP-NADH kinases. The phenotypic analysis of the single, double and
      triple mutants, which was unexpectedly found to be viable, for UTR1, YEF1 and
      POS5 demonstrated the critical contribution of Pos5p to mitochondrial function
      and survival at 37 degrees C and the critical contribution of Utr1p to growth in
      low iron medium. The contributions of the other two enzymes were also
      demonstrated; however, these were observed only in the absence of the critical
      contributor, which was supported by complementation for some pos5 phenotypes by
      the overexpression of UTR1 and YEF1. The viability of the triple mutant suggested
      that a 'novel' enzyme, whose primary structure is different from those of all
      known NAD and NADH kinases, probably catalyses the formation of cytosolic NADP in
      S. cerevisiae. Finally, we found that LEU2 of Candida glabrata, encoding beta
      isopropylmalate dehydrogenase and being used to construct the triple mutant,
      complemented some pos5 phenotypes; however, overexpression of LEU2 of S.
      cerevisiae did not. The complementation was putatively attributed to an ability
      of Leu2p of C. glabrata to use NADP as a coenzyme and to supply NADPH.

PMID- 15978041
TI  - Differentiation stage-dependent preferred uptake of basolateral (systemic)
      glutamine into Caco-2 cells results in its accumulation in proteins with a role
      in cell-cell interaction.
AB  - Glutamine is an essential amino acid for enterocytes, especially in states of
      critical illness and injury. In several studies it has been speculated that the
      beneficial effects of glutamine are dependent on the route of supply (luminal or
      systemic). The aim of this study was to investigate the relevance of both routes
      of glutamine delivery to in vitro intestinal cells and to explore the molecular
      basis for proposed beneficial glutamine effects: (a) by determining the relative
      uptake of radiolabelled glutamine in Caco-2 cells; (b) by assessing the effect of
      glutamine on the proteome of Caco-2 cells using a 2D gel electrophoresis
      approach; and (c) by examining glutamine incorporation into cellular proteins
      using a new mass spectrometry-based method with stable isotope labelled
      glutamine. Results of this study show that exogenous glutamine is taken up by
      Caco-2 cells from both the apical and the basolateral side. Basolateral uptake
      consistently exceeds apical uptake and this phenomenon is more pronounced in 5
      day-differentiated cells than in 15-day-differentiated cells. No effect of
      exogenous glutamine supply on the proteome was detected. However, we demonstrated
      that exogenous glutamine is incorporated into newly synthesized proteins and this
      occurred at a faster rate from basolateral glutamine, which is in line with the
      uptake rates. Interestingly, a large number of rapidly labelled proteins is
      involved in establishing cell-cell interactions. In this respect, our data may
      point to a molecular basis for observed beneficial effects of glutamine on
      intestinal cells and support results from studies with critically ill patients
      where parenteral glutamine supplementation is preferred over luminal
      supplementation.

PMID- 15978042
TI  - Tachykinin-related peptide precursors in two cockroach species.
AB  - Tachykinins and tachykinin-related peptides (TKRPs) play major roles in signaling
      in the nervous system and intestine of both invertebrates and vertebrates. Here
      we have identified cDNAs encoding precursors of multiple TKRPs from the
      cockroaches Leucophaea maderae and Periplaneta americana. All nine LemTKRPs that
      had been chemically isolated in earlier experiments could be identified on the
      precursor of L. maderae. Four previously unidentified LemTKRPs were found in
      addition on the precursor. The P. americana cDNA displayed an open reading frame
      very similar to that of L. maderae with 13 different TKRPs. MALDI-TOF mass
      spectra from tissues of both species confirms the presence of all the TKRPs
      encoded on the precursor plus two additional peptides that are cleavage products
      of the N-terminally extended TKRPs. A tissue-specific distribution of TKRPs was
      observed in earlier experiments at isolation from brain and midgut of L. maderae.
      Our data do not suggest a differential gene expression but a different efficacy
      in processing of LemTKRP-2 and Lem/PeaTKRP-3 in the brain and intestine,
      respectively. This results in a gut-specific accumulation of these extended
      peptides, whereas in the brain their cleavage products, LemTKRP-1 and LemTKRP
      3(11-19), are most abundant. Mass spectrometric analysis demonstrated the
      occurrence of the different TKRPs in single glomeruli of the tritocerebrum and in
      cells of the optical lobe.

PMID- 15978043
TI  - Enzymatic properties of wild-type and active site mutants of chitinase A from
      Vibrio carchariae, as revealed by HPLC-MS.
AB  - The enzymatic properties of chitinase A from Vibrio carchariae have been studied
      in detail by using combined HPLC and electrospray MS. This approach allowed the
      separation of alpha and beta anomers and the simultaneous monitoring of
      chitooligosaccharide products down to picomole levels. Chitinase A primarily
      generated beta-anomeric products, indicating that it catalyzed hydrolysis through
      a retaining mechanism. The enzyme exhibited endo characteristics, requiring a
      minimum of two glycosidic bonds for hydrolysis. The kinetics of hydrolysis
      revealed that chitinase A had greater affinity towards higher Mr chitooligomers,
      in the order of (GlcNAc)6 > (GlcNAc)4 > (GlcNAc)3, and showed no activity towards
      (GlcNAc)2 and pNP-GlcNAc. This suggested that the binding site of chitinase A was
      probably composed of an array of six binding subsites. Point mutations were
      introduced into two active site residues - Glu315 and Asp392 - by site-directed
      mutagenesis. The D392N mutant retained significant chitinase activity in the gel
      activity assay and showed approximately 20% residual activity towards
      chitooligosaccharides and colloidal chitin in HPLC-MS measurements. The complete
      loss of substrate utilization with the E315M and E315Q mutants suggested that
      Glu315 is an essential residue in enzyme catalysis. The recombinant wild-type
      enzyme acted on chitooligosaccharides, releasing higher quantities of small
      oligomers, while the D392N mutant favored the formation of transient
      intermediates. Under standard hydrolytic conditions, all chitinases also
      exhibited transglycosylation activity towards chitooligosaccharides and pNP
      glycosides, yielding picomole quantities of synthesized chitooligomers. The D392N
      mutant displayed strikingly greater efficiency in oligosaccharide synthesis than
      the wild-type enzyme.

PMID- 15978044
TI  - Functional hierarchy of plasminogen kringles 1 and 4 in fibrinolysis and plasmin
      induced cell detachment and apoptosis.
AB  - Plasmin(ogen) kringles 1 and 4 are involved in anchorage of plasmin(ogen) to
      fibrin and cells, an essential step in fibrinolysis and pericellular proteolysis.
      Their contribution to these processes was investigated by selective
      neutralization of their lysine-binding function. Blocking the kringle 1 lysine
      binding site with monoclonal antibody 34D3 fully abolished binding and activation
      of Glu-plasminogen and prevented both fibrinolysis and plasmin-induced cell
      detachment-induced apoptosis. In contrast, blocking the kringle 4 lysine-binding
      site with monoclonal antibody A10.2 did not impair its activation although it
      partially inhibited plasmin(ogen) binding, fibrinolysis and cell detachment. This
      remarkable, biologically relevant, distinctive response was not observed for
      plasmin or Lys-plasminogen; each antibody inhibited their binding and activation
      of Lys-plasminogen to a limited extent, and full inhibition of fibrinolysis
      required simultaneous neutralization of both kringles. Thus, in Lys-plasminogen
      and plasmin, kringles 1 and 4 act as independent and complementary domains, both
      able to support binding and activation. We conclude that Glu-/Lys-plasminogen and
      plasmin conformations are associated with transitions in the lysine-binding
      function of kringles 1 and 4 that modulate fibrinolysis and pericellular
      proteolysis and may be of biological relevance during athero-thrombosis and
      inflammatory states. These findings constitute the first biological link between
      plasmin(ogen) transitions and functions.

PMID- 15978045
TI  - Fatty acid desaturases from the microalga Thalassiosira pseudonana.
AB  - Analysis of a draft nuclear genome sequence of the diatom Thalassiosira
      pseudonana revealed the presence of 11 open reading frames showing significant
      similarity to functionally characterized fatty acid front-end desaturases. The
      corresponding genes occupy discrete chromosomal locations as determined by
      comparison with the recently published genome sequence. Phylogenetic analysis
      showed that two of the T. pseudonana desaturase (Tpdes) sequences grouped with
      proteobacterial desaturases that lack a fused cytochrome b5 domain. Among the
      nine remaining gene sequences, temporal expression analysis revealed that seven
      were expressed in T. pseudonana cells. One of these, TpdesN, was previously
      characterized as encoding a Delta11-desaturase active on palmitic acid. From the
      six remaining putative desaturase genes, we report here that three, TpdesI,
      TpdesO and TpdesK, respectively encode Delta6-, Delta5- and Delta4-desaturases
      involved in production of the health beneficial polyunsaturated fatty acid DHA
      (docosahexaenoic acid). Furthermore, we show that one of the remaining genes,
      TpdesB, encodes a Delta8-sphingolipid desaturase with strong preference for
      dihydroxylated substrates.

PMID- 15978046
TI  - A new molecular tool for transgenic diatoms: control of mRNA and protein
      biosynthesis by an inducible promoter-terminator cassette.
AB  - Research in diatom biology has entered the postgenomic era since the recent
      completion of the Thalassiosira pseudonana genome project. However, the molecular
      tools available for genetic manipulation of diatoms are still sparse, impeding
      the functional analysis of diatom genes in vivo. Here we describe the first
      method for inducible gene expression in transgenic diatoms. This method uses a
      DNA cassette containing both promoter (Pnr) and terminator (Tnr) elements derived
      from the nitrate reductase gene of the diatom Cylindrotheca fusiformis. By using
      green fluorescent protein (gfp) cDNA as a reporter gene, it is demonstrated that
      gene expression under the control of the Pnr/Tnr cassette is switched off when
      cells are grown in the presence of ammonium ions and becomes switched on within 4
      h when cells are transferred to medium containing nitrate. Incubating cells in
      nitrogen-free medium switches on transcription of the gfp gene, yet gfp mRNA does
      not become translated into protein. This block on translation is released by the
      addition of nitrate, resulting in rapid onset of GFP production with a
      drastically reduced delay time of only 1 h. Altogether we have demonstrated that
      the Pnr/Tnr cassette enables inducible gene expression and control of both the
      level and timing of mRNA and protein expression in transgenic diatoms.

PMID- 15978047
TI  - Structural and functional evidence for a singular repertoire of BMP receptor
      signal transducing proteins in the lophotrochozoan Crassostrea gigas suggests a
      shared ancestral BMP/activin pathway.
AB  - The transforming growth factor beta (TGF-beta) superfamily includes bone
      morphogenetic proteins, activins and TGF-betasensu stricto (s.s). These ligands,
      which transduce their signal through a heteromeric complex of type I and type II
      receptors, have been shown to play a key role in numerous biological processes
      including early embryonic development in both deuterostomes and ecdyzozoans.
      Lophochotrozoans, the third major group of bilaterian animals, have remained in
      the background of the molecular survey of metazoan development. We report the
      cloning and functional study of the central part of the BMP pathway machinery in
      the bivalve mollusc Crassostrea gigas (Cg-BMPR1 type I receptor and Cg
      TGFbetasfR2 type II receptor), showing an unusual functional mode of signal
      transduction for this superfamily. The use of the zebrafish embryo as a reporter
      organism revealed that Cg-BMPR1, Cg-TGFbetasfR2, Cg-ALR I, an activin Type I
      receptor or their dominant negative acting truncated forms, when overexpressed
      during gastrulation, resulted in a range of phenotypes displaying severe
      disturbance of anterioposterior patterning, due to strong modulations of
      ventrolateral mesoderm patterning. The results suggest that Cg-BMPR1, and to a
      certain degree Cg-TGFbetasfR2 proteins, function in C. gigas in a similar way to
      their zebrafish orthologues. Finally, based on phylogenetic analyses, we propose
      an evolutionary model within the complete TGF-beta superfamily. Thus, evidence
      provided by this study argues for a possible conserved endomesoderm/ectomesoderm
      inductive mechanism in spiralians through an ancestral BMP/activin pathway in
      which the singular, promiscuous and probably unique Cg-TGFbetasfR2 would be the
      shared type II receptor interface for both BMP and activin ligands.

PMID- 15978048
TI  - A mouse model for in vivo tracking of the major dust mite allergen Der p 2 after
      inhalation.
AB  - Inhaled environmental antigens, i.e. allergens, cause allergic symptoms in
      millions of patients worldwide. As little is known about the fate of an allergen
      upon inhalation, we addressed this issue for a major dust mite allergen, Der p 2.
      First, a model for Der p 2-sensitization was established in C57BL/6 J mice, in
      which sensitized mice mounted a Der p 2-specific IgE-response with eosinophilic
      lung inflammation after allergen challenge in the airways. In this model, we
      applied recombinant Der p 2 carrying a novel C-terminal tetrapeptide Sel-tag
      enabling labelling with the gamma-emitting radionuclide 75Se at a single
      selenocysteine residue ([75Se]Der p 2). In vivo tracking of intratracheally
      administered [75Se]Der p 2 using whole-body autoradiography revealed that
      [75Se]Der p 2-derived radioactivity persisted in the lungs of sensitized mice as
      long as 48 h. Radioactivity was also detected in kidneys, liver and in enlarged
      lung-associated lymph nodes. Interestingly, a larger proportion of radioactivity
      was found in the lungs of sensitized compared with nonsensitized mice 24 h after
      intratracheal instillation of [75Se]Der p 2. A radioactive protein corresponding
      to intact Der p 2 could only be detected in the lungs, whereas [75Se]Der p 2
      derived radioactivity was recovered in known selenoproteins both in lung and
      other organs. Hence, using the recently developed Sel-tag method in a mouse model
      for Der p 2-sensitization, we could track the fate of an inhaled allergen in
      vivo. Based upon our findings, we conclude that the inflammatory state of the
      lung influences the rate of metabolism and clearance of Der p 2. Thus, an
      allergic response to the inhaled allergen may lead to prolonged retention of Der
      p 2 in the lung.

PMID- 15978049
TI  - Gene expression in response to endoplasmic reticulum stress in Arabidopsis
      thaliana.
AB  - Eukaryotic cells respond to the accumulation of unfolded proteins in the
      endoplasmic reticulum (ER). In this case, so-called unfolded protein response
      (UPR) genes are induced. We determined the transcriptional expression of
      Arabidopsis thaliana UPR genes by fluid microarray analysis of tunicamycin
      treated plantlets. Two hundred and fifteen up-regulated genes and 17 down
      regulated ones were identified. These genes were reanalyzed with functional DNA
      microarrays, using DNA fragments cloned through fluid microarray analysis.
      Finally, 36 up-regulated and two down-regulated genes were recognized as UPR
      genes. Among them, the up-regulation of genes related to protein degradation
      (HRD1, SEL-1L/HRD3 and DER1), regulation of translation (P58(IPK)), and apoptosis
      (BAX inhibitor-1) was reconfirmed by real-time reverse transcriptase-PCR. The
      induction of SEL-1L protein in an Arabidopsis membrane fraction on tunicamycin
      treatment was demonstrated. Phosphorylation of initiation factor-2alpha, which
      was inhibited by P58(IPK), was decreased in tunicamycin-treated plantlets.
      However, regulatory changes in translation caused by ER stress were not detected
      in Arabidopsis. Plant cells appeared to have a strategy for overcoming ER stress
      through enhancement of protein folding activity, degradation of unfolded
      proteins, and regulation of apoptosis, but not regulation of translation.

PMID- 15978050
TI  - Inhibition of the mitochondrial calcium uniporter by the oxo-bridged dinuclear
      ruthenium amine complex (Ru360) prevents from irreversible injury in postischemic
      rat heart.
AB  - Mitochondrial calcium overload has been implicated in the irreversible damage of
      reperfused heart. Accordingly, we studied the effect of an oxygen-bridged
      dinuclear ruthenium amine complex (Ru360), which is a selective and potent
      mitochondrial calcium uniporter blocker, on mitochondrial dysfunction and on the
      matrix free-calcium concentration in mitochondria isolated from reperfused rat
      hearts. The perfusion of Ru360 maintained oxidative phosphorylation and prevented
      opening of the mitochondrial permeability transition pore in mitochondria
      isolated from reperfused hearts. We found that Ru360 perfusion only partially
      inhibited the mitochondrial calcium uniporter, maintaining the mitochondrial
      matrix free-calcium concentration at basal levels, despite high concentrations of
      cytosolic calcium. Additionally, we observed that perfused Ru360 neither
      inhibited Ca2+ cycling in the sarcoplasmic reticulum nor blocked ryanodine
      receptors, implying that the inhibition of ryanodine receptors cannot explain the
      protective effect of Ru360 in isolated hearts. We conclude that the maintenance
      of postischemic myocardial function correlates with an incomplete inhibition of
      the mitochondrial calcium uniporter. Thus, the chemical inhibition by this
      molecule could be an approach used to prevent heart injury during reperfusion.

PMID- 15978051
TI  - The functional role of cysteines adjacent to the NRY motif of the human MT1
      melatonin receptor.
AB  - All G protein-coupled melatonin receptors have two conserved cysteines in the
      interphase between transmembrane helix III and the second intracellular loop, in
      the region assumed important in receptor/G protein coupling. The cysteines are
      also potential targets of receptor S-nitrosylation. The effects of site-directed
      mutagenesis of these cysteines in the human MT1 melatonin receptor were
      investigated. The cysteines were mutated into serines either individually or as a
      pair and stable Chinese hamster ovary cell lines expressing the wild-type and
      mutant MT1 receptors were created. Receptor expression level, subcellular
      localization, ligand binding and G protein activation of the cell lines were
      analyzed. Serine substitution of C127 (Cys(3.52)) did not affect the ligand
      binding affinity and agonist potency but had an influence on receptor trafficking
      and G protein activation capacity. Serine substitution of C130 (Cys(3.55))
      resulted in a decrease in the potency of melatonin to activate G proteins. When
      both cysteines were mutated into serines, normal MT1 receptor binding and
      activation were abolished. Computer modeling revealed that the mutations did not
      change the structure of the ligand binding pocket. Cysteine S-nitrosylation had
      no influence on G protein activation through MT1 receptors. Taken together, these
      data show that the two conserved cysteines in the end of transmembrane domain III
      of the MT1 melatonin receptor, especially C130 (Cys(3.55)), are needed for normal
      G protein activation and receptor trafficking.

PMID- 15978052
TI  - Antiproliferative activity of melatonin by transcriptional inhibition of cyclin
      D1 expression: a molecular basis for melatonin-induced oncostatic effects.
AB  - Melatonin is endowed with a growth inhibitory effect in MCF-7 breast cancer cells
      whose mechanism has been related to an antiestrogenic activity exerted by
      inhibition of binding of the estradiol-estrogen receptor complex to its DNA
      responsive element. Looking for downstream gene determinants of this effect, we
      performed a transcriptome profiling by high-density microarrays of estrogen
      treated MCF-7 cells exposed or not to melatonin. We found that cyclin D1 was one
      of the main downregulated genes by melatonin. Validation experiments clearly
      confirm that in MCF-7 cells the estrogen-induced growth inhibitory activity of
      melatonin is consistently associated with inhibition of estrogen-elicited cyclin
      D1 induction. This effect is almost purely transcriptional. Reporter gene assays
      indicate that the same portion of the cyclin D1 promoter which confers estrogen
      sensitivity, encompassing a potential cAMP responsive element binding site, is
      repressed by melatonin. Transcriptional downregulation of cyclin D1 is the key
      molecular event for melatonin's antiproliferative activity, as this activity can
      be completely and selectively rescued by transient cyclin D1 overexpression.
      Finally, we provide indirect evidence that the effect of melatonin on the cyclin
      D1 promoter is mediated by the c-jun and ATF-2 proteins, known to bind the
      minimal estrogen-sensitive cyclin D1 promoter element. These findings establish
      for the first time a molecular link between melatonin and its effects on the cell
      cycle, providing at the same time a rationale for its use in adjuvant
      chemotherapy.

PMID- 15978053
TI  - Coexpression of MT1 and RORalpha1 melatonin receptors in the Syrian hamster
      Harderian gland.
AB  - Melatonin acts through several specific receptors, including membrane receptors
      (MT(1) and MT(2)) and members of the RZR/ROR nuclear receptors family, which have
      been identified in a large variety of mammalian and nonmammalian cells types.
      Both membrane and nuclear melatonin receptors have been partially characterized
      in Harderian gland of the Syrian hamster. Nevertheless, the identities of these
      receptors were unknown until this study, where the coexistence of MT(1) and
      RORalpha(1) in this gland was determined by nested RT-PCR followed by amplicon
      sequencing and Western-blot. Furthermore, the cellular localization of both
      receptors was determined by immunohistochemistry. Thus, MT(1) receptor was
      localized exclusively at the basal side of the cell acini, supporting the
      hypothesis that this receptor is activated by the pineal-synthesized melatonin.
      On the contrary, although a RORalpha(1)-immunoreactivity was observed in nuclei
      of epithelial cells of both sexes, an extranuclear specific staining, which was
      more frequently among those cells of males, was also seen. The implication of
      this possible nuclear exclusion of RORalpha(1) on the role of this indoleamine
      against oxidative stress is discussed.

PMID- 15978054
TI  - Antioxidant activity of melatonin and a pinoline derivative on linoleate model
      system.
AB  - This study aimed at investigating the in vitro protective effects of GWC22, a
      novel pinoline derivative [6-ethyl-1-(3-methoxyphenyl)-2-propyl-1,2,3,4
      tetrahydro-beta-carboline] chlorhydrate, against radiation-induced oxidation of
      linoleate initiated by hydroxyl radicals ((*)OH). Using linoleate micelles (10(
      2) m) as lipid model, two indexes of peroxidation have been measured, i.e.
      conjugated dienes and hydroperoxides. Similar determinations were performed with
      melatonin in order to compare the protective effects of the two compounds. It was
      observed that, the higher the concentration of GWC22 (or melatonin) (3 x 10(-5)
      to 10(-4) m), the stronger the antioxidant ability. In these in vitro assays,
      GWC22 showed a better antioxidant effect than melatonin for a given antioxidant
      concentration. A reaction scheme has been proposed to explain the inhibitory
      effect of an antioxidant via the propagating steps of the lipid peroxidation.
      Indeed, we have suggested that melatonin and GWC22 may compete with the fatty
      acid to scavenge lipid peroxyl radicals (LOO(*)). We have estimated a lower limit
      for the LOO(*) rate constant for GWC22 (>/=1.4 x 10(5)/m/s) and for melatonin
      (>/=2.8 x 10(4)/m/s) assuming that the k-value of the propagating step in
      linoleate (LOO(*) + linoleate) was 1.4 x 10(3)/m/s. The difference of reactivity
      between melatonin and GWC22 in this model system is assumed to be related to
      their relative lipophilicity.

PMID- 15978055
TI  - Melatonin protects against MPTP/MPP+ -induced mitochondrial DNA oxidative damage
      in vivo and in vitro.
AB  - The effects of melatonin on the mitochondrial DNA (mtDNA) damage induced by 1
      methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4
      phenylpyridine ion (MPP(+)) were investigated both in vivo and in vitro. MPTP (24
      mg/kg, s.c.) induced a rapid increase in the immunoreactivity of 8-hydroxyguanine
      (8-oxoG), a common biomarker of DNA oxidative damage, in the cytoplasm of neurons
      in the Substantia Nigra Compact of mouse brain. Melatonin preinjection (7.5, 15
      or 30 mg/kg, i.p.) dose-dependently prevented MPTP-induced DNA oxidative damage.
      In SH-SY5Y cells, MPP(+) (1 mm) increased the immunoreactivity of 8-oxoG in the
      mitochondria at 1 hr and in the nucleus at 3 hr after treatment. Melatonin (200
      microm) preincubation significantly attenuated MPP(+)-induced mtDNA oxidative
      damage. Furthermore, MPP(+) time-dependently increased the accumulation of
      mitochondrial oxygen free radicals (mtOFR) from 1 to 24 hr and gradually
      decreased the mitochondrial membrane potential (Psim) from 18 to 36 hr after
      incubation. At 72 hr after incubation, MPP(+) caused cell death in 49% of the
      control. However, melatonin prevented MPP(+)-induced mtOFR generation and Psim
      collapse, and later cell death. The present results suggest that cytoprotection
      of melatonin against MPTP/MPP(+)-induced cell death may be associated with the
      attenuation of mtDNA oxidative damage via inhibition of mtOFR generation and the
      prevention of Psim collapse.

PMID- 15978056
TI  - Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic
      neuropathy.
AB  - The present study has been designed to determine melatonin levels in type 2
      diabetic patients and test the relationship between the autonomic nervous system
      and melatonin dynamics. Thirty-six type 2 diabetic patients and 13 age-matched
      healthy subjects were recruited for the study. Circadian rhythm of melatonin
      secretion was assessed by measuring serum melatonin concentrations between 02:00
      04:00 and 16:00-18:00 hr. Melatonin dynamics were re-evaluated with respect to
      autonomic nervous system in diabetic patients with autonomic neuropathy who were
      diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and
      24-hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal
      melatonin surge were low in the diabetic group (P = 0.027 and 0.008
      respectively). Patients with autonomic neuropathy revealed decreased melatonin
      levels both at night and during day when compared with healthy controls (P <
      0.001 and 0.004 respectively) while the melatonin dynamics were similar to
      controls in patients without autonomic neuropathy. Nocturnal melatonin level was
      positively correlated with nocturnal high and low frequency components of HRV (P
      = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at
      night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy.
      We found a negative correlation between nocturnal melatonin levels and the degree
      of systolic blood pressure decrease at night (r = -0.478, P = 0.045). As a
      conclusion this study has shown that circadian rhythm of melatonin secretion is
      blunted in type 2 diabetic patients and there is a complex relationship between
      various components of autonomic nervous system and melatonin secretion at night.
      Among the patients with autonomic neuropathy those with more preserved HRV and
      the systolic nondippers (<10% reduction in blood pressure during the night
      relative to daytime values) have more pronounced melatonin surge at night.

PMID- 15978057
TI  - Learning and memory deficits in rats induced by chronic thinner exposure are
      reversed by melatonin.
AB  - Thinner is a neurotoxic mixture which is widely used as an aromatic industrial
      solvent. This product has been shown to cause functional and structural changes
      in the central nervous system. We investigated the effect of exposure to high
      concentrations (3000 p.p.m.) of thinner for 45 days (1 hr/day) on cognitive
      functions and the levels of neural cell adhesion molecules (NCAM) and lipid
      peroxidation products (LPO) in the hippocampus, cortex and cerebellum of rats.
      The actions of melatonin on the effects produced by thinner exposure were also
      tested. Thinner exposure caused a significant increase in LPO (malondialdehyde
      and 4-hydroxyalkenals) in all brain regions. Melatonin administration
      significantly reduced LPO and elevated glutathione levels in the brain regions.
      NCAM (180 kDa) was significantly decreased in hippocampus and cortex of thinner
      exposed rats. Furthermore, thinner-exposed rats showed cognitive deficits in
      passive avoidance and Morris water maze tasks, whereas in the rats chronically
      treated with melatonin these effects were reversed. This study indicates that
      treatment with melatonin prevents learning and memory deficits caused by thinner
      exposure possibly by reducing oxidative stress and regulating neural plasticity.

PMID- 15978058
TI  - Microcirculatory effects of melatonin in rat skeletal muscle after prolonged
      ischemia.
AB  - The purpose of this study was to determine microcirculatory effects and response
      of nitric oxide synthase (NOS) to melatonin in skeletal muscle after prolonged
      ischemia. A vascular pedicle isolated rat cremaster muscle model was used. Each
      muscle underwent 4 hr of zero-flow warm ischemia followed by 2 hr of reperfusion.
      Melatonin (10 mg/kg) or saline as a vehicle was given by intraperitoneal
      injection at 30 min prior to reperfusion and the same dose was given immediately
      after reperfusion. After reperfusion, microcirculation measurements including
      arteriole diameter, capillary perfusion and endothelial-dependent and 
      independent vasodilatation were performed. The cremaster muscle was then
      harvested to measure endothelial NOS (eNOS) and inducible NOS (iNOS) gene
      expression and enzyme activity. Three groups of rats were used: sham
      ischemia/reperfusion (I/R), vehicle + I/R and melatonin + I/R. As compared with
      vehicle + I/R group, administration of melatonin significantly enhanced arteriole
      diameter, improved capillary perfusion, and attenuated endothelial dysfunction in
      the microcirculation of skeletal muscle after 4 hr warm ischemia. Prolonged warm
      ischemia followed by reperfusion significantly depressed eNOS gene expression and
      constitutive NOS activity and enhanced iNOS gene expression. Administration of
      melatonin did not significantly alter NOS gene expression or activity in skeletal
      muscle after prolonged ischemia and reperfusion. Melatonin provided a significant
      microvascular protection from reperfusion injury in skeletal muscle. This
      protection is probably attributable to the free radical scavenging effect of
      melatonin, but not to its anti-inflammatory effect.

PMID- 15978059
TI  - Seasonality of pineal gland activity and immune functions in chickens.
AB  - The immunomodulatory action of melatonin in different animal species is already
      well known, although the mechanism(s) by which the indoleamine influences the
      immune system have yet to be fully elucidated. Previously, we have shown both
      anti-inflammatory and opioid-mediated influence of exogenous melatonin on
      thioglycollate-induced peritonitis in young chickens. In the present study, the
      kinetics of peritonitis and splenocyte proliferation were compared in chickens
      reared in both seasons under the same L:D 12:12 conditions. These two aspects of
      the immune response were correlated with the diurnal rhythm of pineal gland
      function, measured by the activity of N-acetyltransferase (NAT), a key enzyme in
      melatonin biosynthesis. The results revealed seasonal changes in the circadian
      rhythm of pineal NAT activity occurring in parallel to the natural local
      geophysical seasons. These changes appeared to influence the development of
      peritonitis and splenocyte responsiveness to mitogenic stimulation in vitro.
      Moreover, the existence of bidirectional communication between the pineal gland
      and the activated immune system was supported by the decreased activity of pineal
      NAT in chickens with peritonitis compared with control birds.

PMID- 15978060
TI  - Serum melatonin circadian profiles in women suffering from cervical cancer.
AB  - Although there is an increasing evidence that the pineal gland may play a role in
      human malignancy, the studies on melatonin concentrations in different types of
      malignant tumors brought about controversial results. However, changes in
      melatonin concentrations have been observed in some types of human malignant
      tumors. Therefore, we decided to study the circadian melatonin rhythm in patients
      suffering from cervical cancer in different stages of progression and to compare
      them with those in subjects free from neoplastic disease. A total of 45 women
      were analyzed in this study. The subjects were divided into two groups. The first
      group consisted of 31 patients [mean age 52.1 +/- 1.8 yr (mean +/- S.E.M.), range
      32-77 yr] with cervical cancer in various stages of the disease. The second group
      consisted of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/- S.E.M.),
      range 42-63] who served as the control group. Blood samples were collected at
      08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00, and 08:00 hours.
      Melatonin concentration was measured by immunoenzymatic method. There were
      significant differences in circadian melatonin profiles as well as in the area
      under curve among the two studied groups. Melatonin concentrations were
      significantly lower in cancer patients in comparison with healthy individuals.
      Taking into consideration stage of the cervical cancer significantly lower
      melatonin secretion has been found in all subgroups of patients in comparison
      with that of tumor-free control group. Additionally, nocturnal melatonin
      concentrations as well as area under curve were significantly lower in advanced
      stage of cancer (stages 3 and 4) in comparison with patients with preinvasive
      cancer (stage 0) at 24:00, 02:00, and 04:00 hours and patients with stage 1
      disease at 02:00 and 04:00 hours. The results of the present study indicate that
      the presence of cervical cancer influences melatonin levels in women. Moreover,
      stage dependence in reduction of melatonin concentrations has been found.

PMID- 15978061
TI  - Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat
      thymus development: role of the pineal gland.
AB  - To gain insight into the relationship between thymus and pineal gland during rat
      development, the melatonin content as well as the activity and expression of the
      two key enzymes for melatonin biosynthesis, i.e. N-acetyltransferase (NAT) and
      hydroxyindole-O-methyltransferase (HIOMT), were studied in the thymus at fetal
      and postnatal stages. Moreover, melatonin-membrane receptor (MT1) expression was
      also analyzed. We found both the expression and activity of thymic NAT and HIOMT
      at 18 days of fetal life. Additionally, there is production of melatonin in the
      thymus as well as MT1 expression at this fetal age. These results show values
      higher in day-time than at night-time. The pineal gland begins to produce
      significant levels of melatonin around postnatal day 16, and this synthesis shows
      a circadian rhythm with high values during the dark period; therefore the
      nocturnal serum melatonin may inhibit thymic melatonin production. To document
      this, we report an increased melatonin content of the thymus in pinealectomized
      rats compared with sham-pinealectomized. In conclusion, these results show, for
      the first time, the presence of the biosynthetic machinery of melatonin and
      melatonin production in developing rat thymus and that the pineal gland may
      regulate this process.

PMID- 15978062
TI  - A novel H28Y mutation in LEC rats leads to decreased NAT protein stability in
      vivo and in vitro.
AB  - Nocturnal melatonin production is reportedly controlled by the rhythms of
      serotonin N-acetyltransferase (NAT, or arylalkylamine N-acetyltransferase). While
      analyzing the melatonin synthetic pathways of Long Evans cinnamon (LEC) rats
      mutant for PINA, a pineal night-specific ATPase defective in Wilson disease, we
      discovered that NAT activity and protein levels are greatly reduced in LEC rats,
      and that the highly conserved histidine 28 is mutated to tyrosine. To study the
      effect of H28Y, we isolated a new strain of rat termed LPN that is mutant for NAT
      but wildtype for both PINA and coat color. Compared with control rats, the LPN
      rats displayed low NAT protein levels and enzyme activities. These results
      suggest that the H28Y mutation in NAT is the cause of reduced NAT levels in vivo.
      The identical H28Y mutation was also found in Sprague-Dawley rats from Zivic
      Miller, suggesting it may be a common mutation in rodents. When analyzed in
      bacterial cells and HEK293 cells, the mutation resulted in reduction of both NAT
      protein stability and catalytic activity, confirming that the in vivo NAT
      phenotype in LPN rats was due to the H28Y mutation. Further analysis of the NAT
      H28Y will focus on the mechanisms of the increased degradation both in vitro and
      in vivo, which will facilitate our understanding of how melatonin synthesis is
      controlled at the molecular level.

PMID- 15978063
TI  - N-acetyltransferase is not the rate-limiting enzyme of melatonin synthesis at
      night.
AB  - Circadian melatonin production in the pineal gland and retina is under the
      control of serotonin N-acetyltransferase (NAT) and hydroxyindole-O
      methyltransferase. Because NAT activity varies diurnally, it has been considered
      both the melatonin rhythm-generating enzyme and the rate-limiting enzyme of
      melatonin synthesis. In rats with dramatically reduced NAT activity due to a H28Y
      mutation in NAT, melatonin levels remained the same as in wildtype controls,
      suggesting that NAT does not determine the rate of melatonin production at night.
      Using a combination of molecular approaches with a sensitive in vivo measurement
      of pineal diurnal melatonin production, we demonstrate that (i) N-acetylserotonin
      (NAS), the enzymatic product of NAT, is present in vast excess in the night
      pineals compared with melatonin; (ii) the continuous increase in NAT protein
      levels at late night does not produce a proportional increase in melatonin; and
      (iii) an increase in NAS in the same animal over several circadian cycles do not
      result in corresponding increase in melatonin output. These results strongly
      suggest that NAT is not the rate-limiting enzyme of melatonin formation at night.

PMID- 15978065
TI  - Functional genomics of bacterial pathogens: from post-genomics to therapeutic
      targets.
AB  - A wealth of new data have become available to the scientific community as a
      result of the sequencing of many pathogen genomes. A recent meeting devoted to
      functional genomics of pathogenic microorganisms confirmed the notion that
      bacterial genomes are not static, because large blocks of genes can be acquired
      or deleted. Less complex environments usually result in reduction in genome size,
      while genome expansion is usually associated with environmental change and
      complexity. During the meeting, pathogenicity and evolutionary aspects were
      illustrated for enteric pathogens, as well as the microevolution of the plague
      bacillus Yersinia pestis. New clues for evolution and pathogenicity were derived
      from comparative genomics of Listeria species. The genomic organization of
      Bartonellae, an emerging human pathogen, was also discussed in an evolutionary
      context. Population and functional genomics of Anthrax-causing bacteria
      highlighted current scientific interest in this potential biothreat.

PMID- 15978066
TI  - Ribosome-based protein folding systems are structurally divergent but
      functionally universal across biological kingdoms.
AB  - In bacteria, Trigger factor (TF) is the first chaperone that interacts with
      nascent polypeptides as soon as they emerge from the exit tunnel of the ribosome.
      TF binds to the ribosomal protein L23 located next to the tunnel exit of the
      large subunit, with which it forms a cradle-like space embracing the polypeptide
      exit region. It cooperates with the DnaK Hsp70 chaperone system to ensure correct
      folding of a number of newly translated cytosolic proteins in Escherichia coli.
      Whereas TF is exclusively found in prokaryotes and chloroplasts, Saccharomyces
      cerevisiae, a eukaryotic microorganism, has a three-member Hsp70-J protein
      complex, Ssb-Ssz-Zuo, which could act as a ribosome-associated folding
      facilitator. In the work reported in this volume of Molecular Microbiology, Rauch
      et al. (2005, Mol Microbiol, doi:10.1111/j.1365-2958.2005.04690.x) examined the
      functional similarity of the ribosome-associated chaperones in prokaryotes and
      eukaryotes. In spite of the fact that TF and the Hsp70-based triad are
      structurally unrelated, TF can bind to the yeast ribosome via Rpl25 (the L23
      counterpart) and can substitute for some, but not all, of the functions assigned
      to Ssb-Ssz-Zuo in yeast. The functional conservation of the ribosome-associated
      chaperones without structural similarity is remarkable and suggests that during
      evolution nature has employed a common design but divergent components to
      facilitate folding of polypeptides as they emerge from the ribosomal exit, a
      fundamental process required for the efficient expression of genetic information.

PMID- 15978067
TI  - Bacterial ribosomal RNA in pieces.
AB  - The exact knowledge on the ribosomal RNA (rRNA) structure is an important
      prerequisite for work with rRNA sequences in bioinformatic analyses and in
      experimental research. Most available rRNA sequences of bacteria are based on
      gene sequences and on similarity analyses using Escherichia coli rRNA as a
      standard. Therefore, it is often overlooked that many bacteria harbour mature
      rRNA 'in pieces'. In some cases, the processing steps during the fragmentation
      lead to the removal of rRNA segments that are usually found in the ribosome. In
      this review, the current knowledge on the mechanisms of rRNA fragmentation and on
      the occurrence of fragmented rRNA in bacteria is summarized, and the
      physiological implications of this phenomenon are discussed.

PMID- 15978068
TI  - Interactions between folding factors and bacterial outer membrane proteins.
AB  - The outer membrane is the first line of contact between Gram-negative bacteria
      and their external environment. Embedded in the outer membrane are integral outer
      membrane proteins (OMPs) that perform a diverse range of tasks. OMPs are
      synthesized in the cytoplasm and are translocated across the inner membrane and
      probably diffuse through the periplasm before they are inserted into the outer
      membrane in a folded and biologically active form. Passage through the periplasm
      presents a number of challenges, due to the hydrophobic nature of the OMPs and
      the choice of membranes into which they can insert. Recently, a number of
      periplasmic proteins and one OMP have been shown to play a role in OMP
      biogenesis. In this review, we describe what is known about these folding factors
      and how they function in a biological context. In particular, we focus on how
      they interact with the OMPs at the molecular level and present a comprehensive
      overview of data relating to a possible effect on OMP folding yield and kinetics.
      Furthermore, we discuss the role of lipo-chaperones, i.e. lipopolysaccharide and
      phospholipids, in OMP folding. Important advances have clearly been made in the
      field, but much work remains to be done, particularly in terms of describing the
      biophysical basis for the chaperone-OMP interactions which so intricately
      regulate OMP biogenesis.

PMID- 15978069
TI  - CTXphi and Vibrio cholerae: exploring a newly recognized type of phage-host cell
      relationship.
AB  - The genes encoding cholera toxin, one of the principal virulence factors of the
      diarrhoeal pathogen Vibrio cholerae, are part of the genome of CTXphi, a
      filamentous bacteriophage. Thus, CTXphi has played a critical role in the
      evolution of the pathogenicity of V. cholerae. Unlike the well-studied F pilus
      specific filamentous coliphages, CTXphi integrates site-specifically into its
      host chromosome and forms stable lysogens. Here we focus on the CTXphi life cycle
      and, in particular, on recent studies of the mechanism of CTXphi integration and
      the factors that govern lysogeny. These and other processes illustrate the
      remarkable dependence of CTXphi on host-encoded factors.

PMID- 15978070
TI  - Dissecting functional similarities of ribosome-associated chaperones from
      Saccharomyces cerevisiae and Escherichia coli.
AB  - Ribosome-tethered chaperones that interact with nascent polypeptide chains have
      been identified in both prokaryotic and eukaryotic systems. However, these
      ribosome-associated chaperones share no sequence similarity: bacterial trigger
      factors (TF) form an independent protein family while the yeast machinery is
      Hsp70-based. The absence of any component of the yeast machinery results in slow
      growth at low temperatures and sensitivity to aminoglycoside protein synthesis
      inhibitors. After establishing that yeast ribosomal protein Rpl25 is able to
      recruit TF to ribosomes when expressed in place of its Escherichia coli homologue
      L23, the ribosomal TF tether, we tested whether such divergent ribosome
      associated chaperones are functionally interchangeable. E. coli TF was expressed
      in yeast cells that lacked the endogenous ribosome-bound machinery. TF associated
      with yeast ribosomes, cross-linked to yeast nascent polypeptides and partially
      complemented the aminoglycoside sensitivity, demonstrating that ribosome
      associated chaperones from divergent organisms share common functions, despite
      their lack of sequence similarity.

PMID- 15978071
TI  - The NusA:RNA polymerase ratio is increased at sites of rRNA synthesis in Bacillus
      subtilis.
AB  - Bacterial RNA polymerases (RNAPs) are capable of producing full-length
      transcripts in the absence of additional factors using in vitro assays. However,
      in vivo RNAP can become stalled during the elongation phase of transcription due
      to the presence of various sequence motifs. Subsequently, a host of elongation
      factors are required to modulate the activity of RNAP. NusA, the most intensively
      studied elongation factor, plays a role in increasing RNAP pausing and
      termination. Conversely, it is also important in transcription of rRNA where it
      functions as an anti-termination factor, helping to ensure only full-length
      transcripts are produced. Here we show that NusA is closely associated with RNAP
      within the bacterial nucleoid and that it is preferentially recruited to sites of
      rRNA synthesis. In vivo and in vitro analyses indicate this results in a change
      in stoichiometry of NusA:RNAP from 1:1 to approximately 2:1 at the subcellular
      sites of rRNA synthesis. A model is presented showing how the ratio of NusA:RNAP
      could affect the activity of the elongation complex so that it functions as an
      anti-terminator complex during rRNA synthesis.

PMID- 15978072
TI  - The Escherichia coli baby cell column: a novel cell synchronization method
      provides new insight into the bacterial cell cycle.
AB  - We describe a new method for synchronizing bacterial cells. Cells that have
      transiently expressed an inducible mutant 'sticky' flagellin are adhered to a
      volume of glass beads suspended in a chromatography column though which growth
      medium is pumped. Following repression of flagellin synthesis, newborn cells are
      eluted from the column in large quantities exceeding that of current baby machine
      techniques by approximately 10-fold. Eluted cultures of 'baby cells' are highly
      synchronous as determined by analysis of DNA replication, cell division and other
      events, over time after elution from the column. We also show that use of
      'minutes after elution' as a time metric permits much greater temporal resolution
      among sequential chromosomal events than the commonly used metric of cell size
      (length). The former approach reveals the existence of transient intermediate
      stages that are missed by the latter approach. This finding has two important
      implications. First, at a practical level, the baby cell column is a particularly
      powerful method for temporal analysis. Second, at a conceptual level, replication
      related events are more tightly linked to cell birth (i.e. cell division) than to
      absolute cell mass.

PMID- 15978074
TI  - Development of the endoplasmic reticulum, mitochondrion and apicoplast during the
      asexual life cycle of Plasmodium falciparum.
AB  - Plasmodium parasites are unicellular eukaryotes that undergo a series of
      remarkable morphological transformations during the course of a multistage life
      cycle spanning two hosts (mosquito and human). Relatively little is known about
      the dynamics of cellular organelles throughout the course of these
      transformations. Here we describe the morphology of three organelles (endoplasmic
      reticulum, apicoplast and mitochondrion) through the human blood stages of the
      parasite life cycle using fluorescent reporter proteins fused to organelle
      targeting sequences. The endoplasmic reticulum begins as a simple crescent-shaped
      organelle that develops into a perinuclear ring with two small protrusions,
      followed by transformation into an extensive reticulated network as the parasite
      enlarges. Similarly, the apicoplast and the mitochondrion grow from single,
      small, discrete organelles into highly branched structures in later-stage
      parasites. These branched structures undergo an ordered fission - apicoplast
      followed by mitochondrion - to create multiple daughter organelles that are
      apparently linked as pairs for packaging into daughter cells. This is the first
      in-depth examination of intracellular organelles in live parasites during the
      asexual life cycle of this important human pathogen.

PMID- 15978073
TI  - Co-ordinated bacteriocin production and competence development: a possible
      mechanism for taking up DNA from neighbouring species.
AB  - It is important to ensure DNA availability when bacterial cells develop
      competence. Previous studies in Streptococcus pneumoniae demonstrated that the
      competence-stimulating peptide (CSP) induced autolysin production and cell lysis
      of its own non-competent cells, suggesting a possible active mechanism to secure
      a homologous DNA pool for uptake and recombination. In this study, we found that
      in Streptococcus mutans CSP induced co-ordinated expression of competence and
      mutacin production genes. This mutacin (mutacin IV) is a non-lantibiotic
      bacteriocin which kills closely related Streptococcal species such as S.
      gordonii. In mixed cultures of S. mutans and S. gordonii harbouring a shuttle
      plasmid, plasmid DNA transfer from S. gordonii to S. mutans was observed in a CSP
      and mutacin IV-dependent manner. Further analysis demonstrated an increased DNA
      release from S. gordonii upon addition of the partially purified mutacin IV
      extract. On the basis of these findings, we propose that Streptococcus mutans,
      which resides in a multispecies oral biofilm, may utilize the competence-induced
      bacteriocin production to acquire transforming DNA from other species living in
      the same ecological niche. This hypothesis is also consistent with a well-known
      phenomenon that a large genomic diversity exists among different S. mutans
      strains. This diversity may have resulted from extensive horizontal gene
      transfer.

PMID- 15978075
TI  - Dual regulation of genes involved in acetoin biosynthesis and motility/biofilm
      formation by the virulence activator AphA and the acetate-responsive LysR-type
      regulator AlsR in Vibrio cholerae.
AB  - AphA is a quorum sensing-regulated activator that initiates the virulence cascade
      in Vibrio cholerae by cooperating with the LysR-type regulator AphB at the tcpPH
      promoter on the Vibrio pathogenicity island (VPI). To identify the ancestral
      chromosomal genes in V. cholerae regulated by AphA, we carried out a microarray
      analysis and show here that AphA influences the expression of 15 genes not
      associated with the VPI. One set of genes strongly repressed by AphA is involved
      in the biosynthesis of acetoin, a product synthesized by a variety of bacteria
      that plays a role in preventing intracellular acidification and which is
      essential for the viability of V. cholerae in the presence of glucose. Also
      present in this operon are two putative signal transduction proteins with EAL and
      GGDEF domains that oppositely influence motility and biofilm formation. Gel
      mobility shift assays show that AphA binds to a site upstream of the first gene
      in the acetoin operon. Transcriptional lacZ fusions indicate that at low cell
      density AphA represses the expression of the acetoin genes up to 15-fold. Voges
      Proskauer tests confirm that deletion of AphA increases the production of acetoin
      under non-inducing conditions and also that the LysR-type regulator AlsR
      divergently transcribed from the operon is required for its production. This is
      the first report of a specific repressor protein involved in the transcriptional
      control of acetoin production as well as the co-regulation of these genes with
      those that influence motility and biofilm formation. The results here provide a
      model for the dual regulation of these processes by acetate and quorum sensing
      through AlsR and AphA.

PMID- 15978076
TI  - Contributions of protein structure and gene position to the compartmentalization
      of the regulatory proteins sigma(E) and SpoIIE in sporulating Bacillus subtilis.
AB  - At an early stage in endospore formation Bacillus subtilis partitions itself into
      two dissimilar compartments with unique developmental fates. Transcription
      appropriate to each compartment is initiated by the activation of compartment
      specific RNA polymerase sigma subunits, sigma(E) in the mother cell and sigma(F)
      in the forespore. Among the possible factors contributing to the compartment
      specificity of sigma(E) and sigma(F) is the selective accumulation of the
      sigma(E) protein in the mother cell and that of SpoIIE, a regulatory phosphatase
      essential to the activation of sigma(F), in the forespore. In the current work,
      fluorescent microscopy is used to investigate the contributions of sigma(E) and
      SpoIIE's protein structures, expression and the genetic asymmetry that develops
      during chromosome translocation into the forespore on their abundance in each
      compartment. Time of entry of the spoIIE and sigE genes into the forespore was
      found to have a significant effect on the enrichment of their products in one or
      the other compartment. In contrast, the structures of the proteins themselves do
      not appear to promote their transfer to a particular compartment, but nonetheless
      contribute to compartmentalization by facilitating degradation in the compartment
      where each protein's activity would be inappropriate.

PMID- 15978077
TI  - Direct binding of the quorum sensing regulator CepR of Burkholderia cenocepacia
      to two target promoters in vitro.
AB  - Burkholderia cenocepacia is an opportunistic human pathogen that can aggressively
      colonize the cystic fibrosis lung. This organism has a LuxR/LuxI-type quorum
      sensing system that enables cell-cell communication via exchange of acyl
      homoserine lactones (AHLs). The CepR and CepI proteins constitute a global
      regulatory system, controlling expression of at least 40 genes, including those
      controlling swarming motility and biofilm formation. In this study, we isolated
      seven lacZ fusions in a clinical isolate of B. cenocepacia that are inducible by
      octanoyl-HSL. Induction of all of these genes requires CepR. The cepI promoter
      was tested for induction by a set of 33 synthetic autoinducers and analogues, and
      was most strongly induced by long-chain AHLs lacking 3-oxo substitutions.
      Expression of this promoter was inhibited by high concentrations of three
      different autoinducers, each having six-carbon acyl chains. When CepR protein was
      overproduced in Escherichia coli, it accumulated in a soluble form in the
      presence of octanoyl-HSL, but accumulated only as insoluble inclusion bodies in
      its absence. Purified CepR-OHL complexes bound to specific DNA sequences at the
      cepI and aidA promoters with high specificity. These binding sites included a 16
      nucleotide imperfect dyad symmetry. Both CepR binding sites are centred
      approximately 44 nucleotides upstream of the respective transcription start
      sites.

PMID- 15978078
TI  - A genetic screen identifies genes and sites involved in pilin antigenic variation
      in Neisseria gonorrhoeae.
AB  - It has previously been shown that the frequency of pilin antigenic variation in
      Neisseria gonorrhoeae (the gonococcus, Gc) is regulated by iron availability. To
      identify factors involved in pilin variation in an iron-dependent or an iron
      independent manner, we conducted a genetic screen of transposon-mutated gonococci
      using a pilus-dependent colony morphology phenotype to detect antigenic variation
      deficient mutants. Forty-six total mutants representing insertions in 30
      different genes were shown to have reduced colony morphology changes resulting
      from impaired pilin variation. Five mutants exhibited an iron-dependent decrease
      in pilin variation, while the remaining 41 displayed an iron-independent decrease
      in pilin variation. Based on the levels of antigenic variation impairment, we
      defined the genes as being essential for, important for, or involved in antigenic
      variation. DNA repair and DNA transformation frequencies of each mutant were
      measured to determine whether other recombination-based processes were also
      affected in the mutants. Each mutant was placed into one of six classes based on
      their pilin variation, DNA repair and DNA transformation phenotypes. Among the
      many genes identified, recR is shown to be an additional member of the gonococcal
      RecF-like recombination pathway. In addition, recG and ruvA represent the first
      evidence that the processing of Holliday junctions is required for pilin
      antigenic variation. Moreover, two independent insertions in a non-coding region
      upstream of the pilE gene suggest that cis-acting sequences important for pilin
      variation are found in that region. Finally, insertions that effect expression of
      the thrB and thrC genes suggest that molecules in the threonine biosynthetic
      pathway are important for pilin variation. Many of the other genes identified in
      this genetic screen do not have an obvious role in pilin variation, DNA repair,
      or DNA transformation.

PMID- 15978079
TI  - Effect of 5'-proximal elements on decay of a model mRNA in Bacillus subtilis.
AB  - Previous work showed that a 42-nucleotide sequence from an SP82 bacteriophage
      early RNA functions as a 5' mRNA stabilizer in Bacillus subtilis. Real-time
      reverse transcriptase polymerase chain reaction (RT-PCR) analysis of decay of a
      model mRNA with alterations at the 5'-end was used to elucidate the mechanism of
      SP82-mediated stability. A predicted 5'-terminal stem-loop structure was
      essential for stabilization. Increasing the strength of the 5'-terminal structure
      above a minimum level did not result in increased stability. A thorough analysis
      of the context in which the stabilizing structure occurred included the effects
      of distance from 5'-end, translation of downstream coding sequence, and distance
      between the secondary structure and the ribosome binding site. Our data are
      consistent with the dominant mRNA decay pathway in B. subtilis being 5'-end
      dependent.

PMID- 15978080
TI  - Integration of three signals at the Escherichia coli nrf promoter: a role for Fis
      protein in catabolite repression.
AB  - Expression from the Escherichia coli nrf operon promoter is activated by the
      anaerobically triggered transcription factor, FNR, and by the nitrate/nitrite ion
      controlled response regulators, NarL or NarP, but is repressed by the IHF and Fis
      proteins. Here, we present in vitro studies on the nrf promoter, using
      permanganate footprinting to measure open complex formation, and DNase I
      footprinting to monitor binding of the different regulators and the interactions
      between them. Our results show that open complex formation is completely
      dependent on FNR and is enhanced by NarL, but is repressed by IHF or Fis. NarL
      counteracts repression by IHF but is unable to alter repression by Fis. These
      results suggest mechanisms by which nrf promoter activity is modulated by the
      different factors. Expression from the nrf promoter is known to be repressed in
      rich media, especially in the presence of glucose, but the molecular basis of
      this is not understood. Here, we show that this catabolite repression is relieved
      by mutations that weaken the DNA site for Fis, improve the DNA site for FNR or
      improve the promoter -10 or -35 elements. Hence, Fis protein is a major factor
      responsible for catabolite repression at the nrf promoter, and Fis can override
      activation by FNR and NarL or NarP.

PMID- 15978081
TI  - HxlR, a member of the DUF24 protein family, is a DNA-binding protein that acts as
      a positive regulator of the formaldehyde-inducible hxlAB operon in Bacillus
      subtilis.
AB  - The HxlR protein from Bacillus subtilis belongs to the DUF24 protein family
      (InterPro No. IPR002577) of unknown function. The hxlR gene that encodes this
      protein is located upstream of the hxlAB operon. This operon encodes two key
      enzymes in the ribulose monophosphate pathway that are involved in formaldehyde
      fixation, 3-hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase.
      Expression of the hxlAB operon is induced by the presence of formaldehyde.
      Recombinant HxlR prepared from Escherichia coli showed specific binding to a
      region of DNA upstream of the hxlAB operon. Using gel-retardation and DNase I
      footprinting assays, we identified two 25 bp binding regions for HxlR within the
      upstream DNA. Surface plasmon resonance analyses suggested that two HxlR dimers
      sequentially bound to the DNA. Finally, we demonstrated that each of the two
      binding regions for HxlR was necessary for formaldehyde-induced expression of the
      hxlAB operon in B. subtilis. Thus, we have shown that HxlR is a DNA-binding
      protein that is necessary for formaldehyde-induced expression of hxlAB in B.
      subtilis.

PMID- 15978082
TI  - A chaperone-like HrpG protein acts as a suppressor of HrpV in regulation of the
      Pseudomonas syringae pv. syringae type III secretion system.
AB  - The cloned hrp/hrc cluster of Pseudomonas syringae pv. syringae 61 (Pss61)
      contains 28 proteins, and many of those are assembled into a type III secretion
      system (TTSS) that is responsible for eliciting the hypersensitive response (HR)
      in non-host plants and causing diseases on host plants (Huang et al., 1995).
      hrpG, the second gene in the hrpC operon, encodes a 15.4 kDa cytoplasmic protein
      whose predicted structure is similar to SicP (E-value: 0.19), a TTSS chaperone of
      Salmonella typhimurium. Two non-polar hrpG mutants, Pss61-N826 and Pss61-N674,
      were produced to investigate the biological function of hrpG gene. Pss61-N826,
      generated by replacing the coding sequence of hrpG with an nptII gene lacking
      both the promoter and the terminator, was found to be capable of eliciting the
      wild-type HR; whereas Pss61-N674 generated by replacement of a terminatorless
      nptII gene in the hrpG coding sequence showed the delayed HR phenotype. Northern
      and Western blotting analyses showed that the expression of hrpZ, hrcJ and hrcQb
      genes residing on two different operons in Pss61-N674 was reduced due to the
      nptII promoter-driven constitutive expression of hrpV that codes for a negative
      regulator. Interestingly, a plasmid-borne hrpG can derepress the hrp expression
      in Pss61-N674 and in Pss61 overexpressing HrpV without decreasing the hrpV
      transcript. Moreover, results of yeast two-hybrid assay, pull-down assay and far
      Western analysis show that HrpG and HrpV interact with each other in vivo and in
      vitro. Additionally, HrpV interacts with a positive regulator HrpS according to
      analysis of a yeast two-hybrid system. Based on the results presented in this
      study, we propose that HrpG acts as a suppressor of the negative regulator HrpV
      mediated via protein-protein interaction, leading to modulation of hrp/hrc
      expression subsequently freeing HrpS to promote the activation of other
      downstream hrp/hrc genes.

PMID- 15978083
TI  - A single gene directs both production and immunity of halocin C8 in a
      haloarchaeal strain AS7092.
AB  - Halocin C8 (HalC8) is an extremely stable and hydrophobic microhalocin with 76
      amino acids, and has a wide inhibitory spectrum against the haloarchaea. It is
      derived from the C-terminus of a 283-amino-acid prepro-protein (ProC8), which was
      demonstrated by molecular cloning of the halC8 gene, and verified by the N
      terminal amino acid sequencing as well as MALDI-TOF-MS analysis of the purified
      HalC8. The production of this halocin is controlled through both transcription
      regulation and protein processing: the halC8 transcripts and HalC8 activity
      rapidly increased to maximal levels upon transition from exponential to
      stationary phase. However, while halC8 transcripts remained abundant, the HalC8
      processing was inhibited during stationary phase. Remarkably, agar-diffusion test
      revealed the unprocessed ProC8 and its 207-amino-acid N-terminal peptide (HalI),
      with or without the putative Tat signal sequence, were capable to block the
      halocin activity of HalC8 in vitro. In addition, heterologous expression of HalI
      in Haloarcula hispanica rendered this sensitive strain remarkable resistance to
      HalC8, indicating that HalI encodes the immunity property of the producer. In
      accordance with this immunity function, HalI and ProC8 were both found localized
      on the cellular membrane. Protein interaction assay revealed that HalI likely
      sequestrated the HalC8 activity by specific binding. To our knowledge, this is
      the first report on halocin immunity, and our results that a single gene encodes
      both peptide antibiotic and immunity protein also provide a novel immune
      mechanism for peptide antibiotics.

PMID- 15978084
TI  - Binding sites of VanRB and sigma70 RNA polymerase in the vanB vancomycin
      resistance operon of Enterococcus faecium BM4524.
AB  - The vanB operon of Enterococcus faecium BM4524 which confers inducible resistance
      to vancomycin is composed of the vanR(B)S(B) gene encoding a two-component
      regulatory system and the vanY(B)WH(B)BX(B) resistance genes that are transcribed
      from promoters P(RB) and P(YB) respectively. In this study, primer extension
      revealed transcription start sites at 13 and 48 bp upstream from the start codon
      of vanR(B) and vanY(B), respectively, that allowed identification of -10 and -35
      promoter motifs. The VanR(B) protein was overproduced in Escherichia coli,
      purified and phosphorylated (VanR(B)-P) non-enzymically with acetylphosphate.
      VanR(B)-P and VanR(B) specifically bound to P(RB) and P(YB) promoters. VanR(B)
      bound at a single site at position -32.5 upstream from the P(RB) transcriptional
      start site and at two sites at positions -33.5 and -55.5 upstream from that of
      P(YB). The proximal VanR(B) binding site overlapped the -35 region of both
      promoters. VanR(B) was converted from a monomer to a dimer upon acetylphosphate
      treatment. VanR(B)-P had higher affinity than VanR(B) for its targets and
      appeared more efficient than VanR(B) in promoting open complex formation with
      P(RB) and P(YB). In the absence of regulator, E. coli RNA polymerase was able to
      interact with P(RB) but not with P(YB). Phosphorylation of VanR(B) significantly
      increased promoter interaction with RNA polymerase and led to an extended and
      modified footprint. In vitro transcription assays showed that VanR(B)-P activates
      P(YB) more strongly than P(RB). Analysis of the protected regions revealed one
      copy of a 21 bp sequence in the P(RB) promoter and two copies in the P(YB)
      promoter which may serve as recognition sites for VanR(B) and VanR(B)-P binding
      that are required for transcriptional activation and expression of vancomycin
      resistance.

PMID- 15978085
TI  - Cell cycle-regulated degradation of tmRNA is controlled by RNase R and SmpB.
AB  - The production and removal of regulatory RNAs must be controlled to ensure proper
      physiological responses. SsrA RNA (tmRNA), a regulatory RNA conserved in all
      bacteria, is cell cycle regulated and is important for control of cell cycle
      progression in Caulobacter crescentus. We report that RNase R, a highly conserved
      3' to 5' exoribonuclease, is required for the selective degradation of SsrA RNA
      in stalked cells. Purified RNase R degrades SsrA RNA in vitro, and is kinetically
      competent to account for all SsrA RNA turnover. SmpB, a tmRNA-binding protein,
      protects SsrA RNA from RNase R degradation in vitro, and the levels of SmpB
      protein during the cell cycle correlate with SsrA RNA stability. These results
      suggest that SmpB binding controls the timing of SsrA RNA degradation by RNase R.
      We propose a model for the regulated degradation of SsrA RNA in which RNase R
      degrades SsrA RNA from a non-tRNA-like 3' end, and SmpB specifically protects
      SsrA RNA from RNase R. This model explains the regulation of SsrA RNA in other
      bacteria, and suggests that a highly conserved regulatory mechanism controls SsrA
      activity.

PMID- 15978086
TI  - The transcriptional activator ClgR controls transcription of genes involved in
      proteolysis and DNA repair in Corynebacterium glutamicum.
AB  - Expression of the structural genes encoding the ATP-dependent proteases ClpCP and
      Lon in Corynebacterium glutamicum and Streptomyces lividans is activated by the
      transcriptional regulator ClgR in response to yet unknown environmental stimuli.
      As it was not known whether ClgR controls expression of additional genes we used
      DNA microarrays in order to comprehensively define the ClgR regulon in C.
      glutamicum. The mRNA levels of 16 genes decreased >/= 2-fold in a
      DeltaclgRDeltaclpC mutant (ClgR absent) compared with a DeltaclpC mutant (ClgR
      present). For five genes in four operons (NCgl0748, ptrB, hflX and NCgl0240-recR)
      regulation by ClgR could be independently verified by primer extension analyses
      and confirmation of binding of purified ClgR to the regulatory regions of these
      operons. ptrB encodes an endopeptidase, which is consistent with the proteolytic
      functions of the genes already known to be under ClgR control. However, RecR is
      unrelated to proteolysis but required for recombinational repair of UV-induced
      DNA damage. Possibly ClgR-dependent activation of gene expression is triggered by
      environmental stresses damaging both proteins and nucleic acids, although DNA
      damage induced by UV radiation and mitomycin C treatment did not result in ClgR
      dependent transcriptional activation of any of the newly identified ClgR regulon
      members. In order to functionally analyse the NCgl0748 and hflX genes we have
      constructed C. glutamicum strains with deletions in these genes. The
      DeltaNCgl0748 mutant displayed reduced growth rates in minimal and rich media.
      The NCgl0748 protein was shown to be localized in the cytoplasm only, while the
      HflX pool is equally distributed between cytoplasm and plasma membrane. In order
      to study the proposed degradation of ClgR by ClpCP we have constructed a
      conditional clpP1P2 mutant. Depletion of ClpP1 and ClpP2 in that strain resulted
      in the accumulation of ClgR, indicating that ClgR is in fact a substrate of the
      ClpCP1 and/or ClpCP2 protease in C. glutamicum.

PMID- 15978087
TI  - Cells lacking ClpB display a prolonged shutoff phase of the heat shock response
      in Caulobacter crescentus.
AB  - The heat shock response in Caulobacter crescentus was previously shown to be
      positively regulated by the alternative sigma factor of RNA polymerase (RNAP)
      sigma(32), and negatively modulated by DnaK during the induction phase of the
      heat shock response but not during the recovery phase. In the present work we
      have investigated the involvement of the chaperone ClpB in the control of the
      heat shock response in C. crescentus. Data obtained indicated a role of ClpB in
      downregulation of heat shock protein (HSP) synthesis, as cells lacking this
      chaperone showed a prolonged shutoff phase of the heat shock response. In
      Escherichia coli, it has been proposed that the DnaK chaperone system switches
      transcription back to constitutively expressed genes through simultaneous
      reactivation of heat-aggregated sigma(70), as well as sequestration of sigma(32)
      away from RNAP. In C. crescentus, results obtained with a clpB null mutant
      indicate that ClpB could be involved in the reactivation of the major sigma
      factor sigma(73). In support of this hypothesis, we showed that transcription
      directed from sigma(73)-dependent promoters is not switched back in the clpB null
      mutant during the recovery phase. Furthermore, we observed that resolubilization
      of heat-aggregated sigma(73) is dependent on the presence of ClpB. Our findings
      also indicated that the absence of ClpB made cells more sensitive to heat shock
      and ethanol but not to other stresses, and unable to acquire thermotolerance.

PMID- 15978088
TI  - Factor XIII and the clotting of fibrinogen: from basic research to medicine.

PMID- 15978089
TI  - The benefits of excess EPCR.

PMID- 15978090
TI  - Overexpressing endothelial cell protein C receptor alters the hemostatic balance
      and protects mice from endotoxin.
AB  - Previous studies have shown that blocking endothelial protein C receptor (EPCR)
      protein C interaction results in about an 88% decrease in circulating activated
      protein C (APC) levels generated in response to thrombin infusion and exacerbates
      the response to Escherichia coli. To determine whether higher levels of EPCR
      expression on endothelial cells might further enhance the activation of protein C
      and protect the host during septicemia, we generated a transgenic mouse (Tie2
      EPCR) line which placed the expression of EPCR under the control of the Tie2
      promoter. The mice express abundant EPCR on endothelial cells not only on large
      vessels, but also on capillaries where EPCR is generally low. Tie2-EPCR mice show
      higher levels of circulating APC after thrombin infusion. Upon infusion with
      factor Xa and phospholipids, Tie2-EPCR mice generate more APC, less thrombin and
      are protected from fibrin/ogen deposition compared with wild type controls. The
      Tie2-EPCR animals also generate more APC upon lipopolysaccharide (LPS) challenge
      and have a survival advantage. These results reveal that overexpression of EPCR
      can protect animals against thrombotic or septic challenge.

PMID- 15978091
TI  - The significance of distal vein thrombosis and bilateral disease.

PMID- 15978092
TI  - Changes in the technology of inferior vena cava filters promise improved benefits
      to the patient with less harm, but a paucity of evidence exists.

PMID- 15978093
TI  - Clinical experience with retrievable vena cava filters: results of a prospective
      observational multicenter study.
AB  - BACKGROUND: Retrievable inferior vena cava (IVC) filters offer the attractive
      possibility to be definitive or to be removed when they become unnecessary.
      OBJECTIVE: The purpose of this study was to evaluate the efficacy and the
      likelihood to remove the retrievable IVC filter ALN. METHODS: A total of 30
      patients (13 males and 17 females, mean age 57 +/- 15 years) underwent placement
      of ALN filters. Indications for implantation were acute venous thromboembolism
      (VTE) with a contraindication to anticoagulation in 26 cases (86%), primary
      prophylaxis after major trauma in two cases (7%) or before surgery in two
      patients with very high thromboembolic risk (7%). RESULTS: The filter was
      successfully placed in all patients. After a median follow-up of 18.2 months,
      there were three cases (10%) of trapped emboli within the filter, one case (3%)
      of asymptomatic migration of the filter toward the heart and two patients (7%)
      had deep vein thrombosis (DVT) recurrences. ALN retrieval was attempted through
      transjugular approach in 18 patients (60%) and the maneuver was successful in 14
      of them (78%); when the decision of removal was taken more than 3 months after
      the implantation, the retrieval was possible only in four of eight patients
      (50%). The median implantation period was 123 days (range: 30-345). CONCLUSIONS:
      The present study shows the efficacy of ALN filter; it also demonstrates the
      feasibility and safety of retrieval after a medium-term period of placement.
      Removal after 3 months after implantation can be unsuccessful and maximum
      implantation time requires further studies.

PMID- 15978094
TI  - Focal cerebral ischemia and hemostasis: a PAI-1 conundrum.

PMID- 15978095
TI  - Effects of plasminogen activator inhibitor-1 on ischemic brain injury in
      permanent and thrombotic middle cerebral artery occlusion models in mice.
AB  - BACKGROUND AND OBJECTIVES: Tissue plasminogen activator (t-PA) improves the
      outcome of ischemic stroke by recanalization of occluded vessels, but has
      neurotoxic side effects in experimental stroke models. Here, the effect of
      plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of t-PA, on
      ischemic infarct volume was studied. METHODS: After either permanent ligation or
      thrombotic occlusion of the middle cerebral artery (MCA), infarct volume,
      spontaneous reperfusion of thrombosed MCA, t-PA/PAI-1 complex level, and blood
      brain barrier (BBB) permeability in the ischemic region was studied in transgenic
      mice with overexpression of PAI-1 and wild-type littermate controls and in mice
      with intracerebroventricular injection of human PAI-1. RESULTS: Infarct volume
      was smaller in PAI-1 transgenic mice (2.9 +/- 3.7 mm3, mean +/- SD) than in
      controls (8.9 +/- 5.0 mm3, P < 0.05) after permanent MCA ligation (plasma PAI-1
      level 39 +/- 23 ng mL(-1) in transgenic mice vs. 1.5 +/- 0.6 ng mL(-1) in
      controls), whereas after MCA thrombosis it was larger in transgenics (13.1 +/-
      3.1 mm3) than in controls (8.0 +/- 3.2 mm3, P < 0.05). Spontaneous reperfusion of
      the thrombosed MCA was significantly delayed in transgenic vs. control mice. In
      the ligation model, t-PA/PAI-1 complex levels were higher and BBB disruption was
      more pronounced in the ischemic region. Human PAI-1 injection reduced infarct
      volume by about 50% in wild-type mice but not in t-PA gene deficient mice.
      CONCLUSIONS: High PAI-1 levels reduced infarct volume in the permanent MCA
      ligation model, but enhanced it in the MCA thrombosis model.

PMID- 15978096
TI  - Pathogenic antibodies to coagulation factors. Part II. Fibrinogen, prothrombin,
      thrombin, factor V, factor XI, factor XII, factor XIII, the protein C system and
      von Willebrand factor.

PMID- 15978097
TI  - The incidence of venous thromboembolism in carriers of antithrombin, protein C or
      protein S deficiency associated with the HR2 haplotype of factor V: a family
      cohort study.
AB  - In order to assess whether the HR2 haplotype of the factor V gene (HR2) increases
      the risk of venous thromboembolism (VTE) in carriers of antithrombin (AT),
      protein C (PC) or S (PS) defects, we performed this determination in 336
      subjects, who were family members of 66 symptomatic patients with clotting
      inhibitors defects. We first assessed the presence of previous VTE, and then
      followed prospectively subjects without prior VTE. VTE episodes had occurred in
      26 individuals: 18 in 139 carriers of clotting inhibitors defects alone (annual
      incidence, 0.55%), four in 33 carriers of clotting inhibitors defects combined
      with HR2 (0.52%) and four in 151 non-carriers (0.1%), resulting in a relative
      risk (RR) for VTE of 4.9 (95% CI: 1.7-14.4) and 4.62 (95% CI: 1.2-18.4),
      respectively. After an overall follow-up of 2557 patient-years, VTE episodes
      developed in 12 subjects: nine in 121 carriers of clotting inhibitors defects
      alone (annual incidence, 0.92%), three in 29 carriers of clotting inhibitors
      defects combined with HR2 (1.0%) and none in 147 non-carriers. In family members
      of patients with AT, PC or PS defects the coinheritance of HR2 haplotype does not
      seem to increase the thromboembolic risk.

PMID- 15978098
TI  - Aprotinin and epsilon aminocaproic acid are effective in reducing blood loss
      after primary total hip arthroplasty--a prospective randomized double-blind
      placebo-controlled study.
AB  - A prospective randomized double-blind placebo-controlled study was undertaken to
      determine the efficacy and mechanism of action of two antifibrinolytic drugs
      aprotinin and epsilon aminocaproic acid (EACA) in reducing blood loss in primary
      unilateral total hip arthroplasty (THA). Aprotinin was administered as a bolus of
      2 x 10(6) kallikrein inhibitor units (KIU) followed by 0.5 x 10(6) KIU h(-1) for
      3 h, EACA was given as 10 g over 30 min followed by 5 g over 3 h. The median
      postoperative blood loss 24 h postoperatively was reduced from 450 mL in the
      placebo group to 180 mL for aprotinin (60% reduction, P < 0.001) and to 210 mL
      for EACA (53% reduction, P < 0.01). In this population, there was no reduction in
      the perioperative transfusion requirements. The mechanism of both drugs was
      independent of platelets as indicated by flow cytometric measurement of change of
      their expression of P-selectin, platelet-monocyte aggregates, V/Va and CD40
      ligand. There were no thrombotic or infective complications and no adverse events
      were attributable to use of either drug. Infusion of either aprotinin or EACA at
      the doses described is a safe and effective means of reducing blood loss after
      THA. These therapies provide a means of reducing blood loss in THA patients.

PMID- 15978099
TI  - Chronic venous abnormalities in symptomatic and asymptomatic protein C
      deficiency.
AB  - BACKGROUND: Thrombophilia is a frequent medical condition associated with
      symptomatic deep vein thrombosis (DVT). Unlike other clinical risk factors
      associated with DVT, such as surgery, thrombophilia has not been demonstrated to
      be associated with asymptomatic venous thrombotic events. Our aim was to search
      for asymptomatic sequelae of DVT in a protein C (PC)-deficient family. METHODS:
      We studied 228 individuals from a large kindred with PC deficiency and performed
      a systematic ultrasound examination. RESULTS: Among the 203 patients without a
      known history of venous thrombosis we found seven patients with abnormalities
      indicative of prior asymptomatic thrombosis: six (7.4%) in the PC-deficient group
      (n = 81) and only one (0.8%) in the non-deficient group (n = 122). The relative
      risk for these sequelae associated with PC deficiency was 9.0 (95% CI: 1.1-73.7).
      CONCLUSIONS: These data suggest that chronic venous abnormalities are frequently
      present and that thrombotic events in asymptomatic individuals with familial PC
      deficiency may be underestimated.

PMID- 15978100
TI  - The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome:
      all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency.
AB  - BACKGROUND: Accurate estimates of the incidence of thrombotic thrombocytopenic
      purpura (TTP) are important to assess the resources required for current
      treatments as well as to anticipate the need to develop new treatments. Previous
      estimates have been indirect and have not reported data on patients with ADAMTS
      13 deficiency. OBJECTIVE: To determine the incidence of patients with TTP
      hemolytic uremic syndrome (HUS) in three categories: all patients with clinically
      suspected TTP-HUS, patients with idiopathic TTP-HUS, and patients with severe
      ADAMTS-13 deficiency. METHODS: Incidence rates were estimated from the Oklahoma
      TTP-HUS Registry, analyzing all 206 consecutive patients from January 1, 1996 to
      June 30, 2004 who were treated with plasma exchange for their initial episode of
      clinically suspected TTP-HUS. ADAMTS-13 activity was measured in 186 (90%) of the
      206 patients. RESULTS: The age-sex-race standardized annual incidence rates were
      11.29 x 10(6) (95% CI: 9.70-12.88) for all patients with clinically suspected TTP
      HUS; 4.46 x 10(6) (95% CI: 3.43-5.50) for patients with idiopathic TTP-HUS; and
      1.74 x 10(6) (95% CI: 1.06-2.41) for patients with severe ADAMTS-13 deficiency
      (<5% activity). In all three categories, the incidence rates were greater for
      women and for blacks. For patients with severe ADAMTS-13 deficiency, the age-sex
      standardized incidence rate ratio of blacks to non-blacks was 9.29 (95% CI: 4.33
      19.93). CONCLUSIONS: Accurate incidence rate estimates for all patients with
      clinically suspected TTP-HUS, idiopathic TTP-HUS, and TTP associated with severe
      ADAMTS-13 deficiency have been determined. The greater incidence among women and
      blacks is comparable with their increased risk for other autoimmune disorders.

PMID- 15978102
TI  - Autoantibodies against the endothelial receptor of protein C are associated with
      acute myocardial infarction in young women.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is rare among young women. The
      search for unknown risk factors is warranted. Endothelial protein C receptor
      (EPCR) is largely present at the endothelial surface of large arteries. No
      studies about association of anti-EPCR autoantibodies (anti-EPCR) with AMI are
      available. METHODS: Plasma IgA, IgM and IgG anti-EPCR levels were measured by
      enzyme-linked immunosorbent assay in 165 women younger than 45 years who survived
      a first AMI and 165 healthy women, matched by age and geographical origin.
      RESULTS: Using the 90th percentile of IgA anti-EPCR in the control group, IgA
      anti-EPCR were independently associated with AMI after adjustment for
      cardiovascular risk factors (OR 5.1; 95% CI 1.7-15.6; P = 0.004). The risk
      apparently conferred by IgA anti-EPCR increased dose-dependently (P for trend
      =0.0002). IgM anti-EPCR were less consistently associated with AMI: a significant
      increase in the risk was found when women above the 90th percentile were compared
      with those in the lowest quartile (OR 3.6; 95% CI 1.2-11.5; P = 0.03). IgG anti
      EPCR were similar in patients and controls. A total of 145 patients underwent
      coronary arteriography. IgA or IgM anti-EPCR were not different among patients
      with different degrees of atherosclerotic lesion (anova, P = 0.77 and 0.24,
      respectively). CONCLUSIONS: High levels of IgA and, to a lesser extent, IgM anti
      EPCR, are associated with AMI in young women.

PMID- 15978101
TI  - The specific thromboxane receptor antagonist S18886: pharmacokinetic and
      pharmacodynamic studies.
AB  - OBJECTIVES AND PATIENTS: We conducted a multicenter double-blind
      pharmacokinetic/pharmacodynamic (PK/PD) study of the new oral thromboxane
      receptor antagonist S18886 in 30 patients with peripheral artery disease, who
      were randomized to receive five different oral dosages of S18886 (1, 2.5, 5, 10
      or 30 mg) for 12 weeks (83 days). Primary objective was to determine the effect
      of S18886 on platelet aggregation ex vivo. RESULTS: Pharmacokinetics of S18886
      was linear, with peak plasma levels being reached between 30 min and 2 h and a
      terminal half-life of 5.8-10 h. No significant accumulation of S18886 in plasma
      was observed after repeated dosing. The relationship between the S18886
      concentration and platelet inhibition was examined in terms of U46619-induced
      platelet aggregation. Over the range of doses studied, there was a predictable
      relation between the plasma drug concentration and the degree of platelet
      inhibition at each dose. Maximal inhibition of U46619-induced platelet
      aggregation was achieved within 1 h with all oral doses of S18886, and this
      effect was maintained for at least 12 h. The PK/PD relationship was direct, and
      U46619-induced platelet aggregation was strongly inhibited by S18886 plasma
      concentrations above 10 ng mL(-1). This concentration was thus the minimal
      effective antiplatelet level in this population, and was maintained only by the
      dosages of 10 and 30 mg. The safety profile of S18886 was excellent, whatever the
      unit dose, with no attributable adverse events. CONCLUSION: The results of this
      study, which included modeling and simulation, help identify the minimal
      effective plasma concentration of S18886 required for potent antiplatelet
      efficacy in patients with stable peripheral arterial disease.

PMID- 15978104
TI  - HR2 haplotype in Arab population and patients with venous thrombosis in Kuwait.
AB  - BACKGROUND: Venous thromboembolism (VTE) occurs due to a number of hereditary and
      acquired disorders of hemostasis. A recently identified polymorphism in factor V
      gene (A4070G; named HR2) has been reported to be a possible risk factor for the
      development of VTE, with a high prevalence of 9.5%-15.2% in patients of different
      ethnic groups in different parts of the world. However, the prevalence of HR2 has
      not yet been tested in VTE patients of Arab ethnicity. OBJECTIVES: To study the
      prevalence and possible risk of HR2 haplotype in Arabs. PATIENTS/METHODS: Exactly
      188 VTE patients and 100 healthy subjects, all being of Arab ethnicity, were
      examined for HR2 using Polymerase chain reaction, restriction fragment length
      polymorphism and agarose gel electrophoresis. RESULTS: Data showed that 31
      patients and seven healthy subjects had HR2 haplotype, with a prevalence of 16.5%
      and 7%, respectively. Furthermore, 43 patients (22.9%) had more than one risk
      factor for VTE. CONCLUSIONS: The prevalence of HR2 in Arabs is quite high, with a
      2.62-fold greater risk of developing VTE. Moreover, coexistence of two or more
      genetic/acquired defects of VTE is quite common in Arab patients.

PMID- 15978103
TI  - The first ambulatory screening on thromboembolism: a multicentre, cross
      sectional, observational study on risk factors for venous thromboembolism.
AB  - OBJECTIVES: To assess the prevalence of risk factors for venous thromboembolism
      (VTE) and the prevalence of recent (<1 year) VTE [including superficial vein
      thrombosis (SVT), deep vein thrombosis (DVT) and pulmonary embolism (PE)] amongst
      patients attending general practitioner (GP) surgeries. DESIGN: Multicentre,
      cross-sectional, observational study. SETTING: A total of 1536 GP surgeries.
      PARTICIPANTS: A total of 15 180 adult, co-operative subjects, who had consulted
      their GP for a health disorder and signed the informed consent form.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prevalence of known VTE risk factors
      graded according to importance and prevalence of recent (<1 year) VTE events
      (including SVT), based on interviews. RESULTS: About 1:5 patients had at least
      one strong risk factor and about 1:20 had at least two risk factors, with no
      difference between sexes. The prevalence of strong risk factors increased with
      age. Most were related to medical conditions: history of SVT and/or DVT/PE, heart
      failure and malignancy. About 3:4 women and 2:3 men had at least one moderate to
      weak risk factor; nearly 1:2 women and 1:3 men had at least two moderate to weak
      risk factors. The most common were: history of VTE, smoking, history of
      miscarriage, estrogen therapy, obesity, and varicose veins. Overall, 80% women
      and 67% men had at least one risk factor, and 50% women and 35% men had at least
      two risk factors. The prevalence of recent (<1 year) VTE was 3.4% in women and
      2.4% in men, and increased with age. The majority of cases were SVT in both sexes
      (2.5% in women and 1.5% in men). CONCLUSIONS: The prevalence of risk factors for
      VTE amongst patients attending GP surgeries is high. GPs should bear this in mind
      during their daily practice.

PMID- 15978105
TI  - The plasma hemostatic proteome: thrombin generation in healthy individuals.
AB  - BACKGROUND AND OBJECTIVES: The range of plasma concentrations of hemostatic
      analytes in the population is wide. In this study these components of blood
      coagulation phenotype are integrated in an attempt to predict clinical risk.
      METHODS: We modeled tissue factor (TF)-induced thrombin generation in the control
      population (N = 473) from the Leiden Thrombophilia Study utilizing a numerical
      simulation model. Hypothetical thrombin generation curves were established by
      modeling pro- and anticoagulant factor levels for each individual. These curves
      were evaluated using parameters which describe the initiation, propagation and
      termination phases of thrombin generation, i.e. time to 10 nm thrombin
      (approximate clot time), total thrombin and the maximum rates and levels of
      thrombin generated. RESULTS AND CONCLUSIONS: The time to 10 nm thrombin varied
      over a 3-fold range (2.9-9.5 min), maximum levels varied over a approximately 4
      fold range (200-800 nm), maximum rates varied approximately 4.8-fold (90-435 nm
      min(-1)) and total thrombin varied approximately 4.5-fold (39-177 microm s(-1))
      within this control population. Thrombin generation curves, defined by the
      clotting factor concentrations, were distinguished by sex, age, alcohol
      consumption, body mass index (BMI) and oral contraceptive (OC) use (OC > sex >
      BMI > age). Our results show that the capacity for thrombin generation in
      response to a TF challenge may represent a method to identify an individual's
      propensity for developing thrombosis.

PMID- 15978106
TI  - Determinants of the APTT- and ETP-based APC sensitivity tests.
AB  - BACKGROUND: A reduced sensitivity for activated protein C (APC) is associated
      with an increased risk of venous thrombosis even in the absence of the factor
      (F)V Leiden mutation. This risk has been demonstrated with two APC sensitivity
      tests, which quantify the effects of APC on the activated partial thromboplastin
      time (APTT) and the endogenous thrombin potential (ETP), respectively.
      OBJECTIVES: We examined determinants of both APC sensitivity tests in the control
      group of the Leiden Thrombophilia Study (LETS). METHODS: Multiple linear
      regression analysis was performed with normalized APC-SR(APTT) or APC-SR(ETP) as
      dependent variable and putative determinants [levels of FII, FV, FVII, FVIII,
      FIX, FX, FXI, FXII, FXIII A subunit, FXIII B subunit, protein S total, protein S
      free, protein C, tissue factor pathway inhibitor (TFPI) total, TFPI free,
      antithrombin and fibrinogen] as independent variables. RESULTS AND CONCLUSIONS:
      The major determinant of the APTT-based test was FVIII level, followed by FII
      level. The ETP-based test was influenced most by free protein S and free TFPI
      levels. In both tests FXa formation plays a major role, as the effect of FVIII
      and TFPI on the tests seems to be executed via FXa. The ETP-based test was also
      strongly influenced by oral contraceptive use, even when we adjusted for all the
      clotting factors listed above. This means that the effect of oral contraceptives
      on the ETP-based test is not fully explained by the changes of coagulation factor
      levels investigated in this study, and that the molecular basis of acquired APC
      resistance during use of oral contraceptives remains to be established.

PMID- 15978107
TI  - Obesity enhances the induction of plasminogen activator inhibitor-1 by restraint
      stress: a possible mechanism of stress-induced renal fibrin deposition in obese
      mice.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular/thrombotic diseases are frequently
      induced by a variety of stressors. Obese patients are susceptible to thrombotic
      diseases associated with stress, but the underlying mechanism is still unknown.
      We have begun to investigate the expression of a primary inhibitor of
      fibrinolysis, plasminogen activator inhibitor-1 (PAI-1), in association with
      tissue thrombosis, using restraint-stressed obese mice. METHODS AND RESULTS: We
      analyzed the expression of PAI-1 after restraint (immobilization) stress in
      genetically obese mice in comparison with their lean counterparts. Dramatic
      increases in PAI-1 antigen in plasma and in tissue extracts were observed in the
      obese mice exposed to restraint stress. The induction of PAI-1 mRNA by stress in
      the tissues was also pronounced in the stressed obese mice as compared with the
      lean mice, especially in the hearts and adipose tissues. In situ hybridization
      analysis revealed that strong signals for PAI-1 mRNA were localized in the
      adipocytes, cardiovascular endothelial cells, and renal glomerular cells of the
      stressed obese mice. Histological examination revealed that renal glomerular
      fibrin deposition was detected only in the obese mice after 2 h of restraint
      stress. CONCLUSIONS: Obesity enhances the stress-mediated PAI-1 induction in the
      blood and tissues. This phenomenon may be associated with the increased risk of
      stress-induced renal fibrin deposition in obese subjects.

PMID- 15978108
TI  - TAFI gene haplotypes, TAFI plasma levels and future risk of coronary heart
      disease: the PRIME Study.
AB  - OBJECTIVES: To evaluate the association of thrombin-activatable fibrinolysis
      inhibitor (TAFI) gene polymorphisms with the risk of coronary heart disease (CHD)
      and with TAFI levels measured by a newly developed enzyme-linked immunosorbent
      assay (ELISA) (TAFI-1B1), shown to be a reliable method for detecting
      quantitative variations in circulating TAFI. PATIENTS/METHODS: Six polymorphisms
      (C-2599G, G-438A, Ala147Thr, Thr325Ile, C + 1542G and T + 1583A) were genotyped
      and baseline plasma concentrations of TAFI were measured in a nested case-control
      design as part of the Prospective Epidemiological Study of Myocardial Infarction
      (PRIME) Study. Participants from France and Northern Ireland who had developed a
      CHD event during a 5-year follow-up (n = 321) were compared with 645 population-
      and age-matched control subjects. RESULTS: In France, the Thr147 allele was more
      frequent in cases than in controls (0.41 vs. 0.32; P = 0.02), whereas the reverse
      was observed in Northern Ireland (0.33 vs. 0.38; P = 0.19) (P = 0.01 for
      interaction). No other polymorphism was associated with CHD risk. Consistent with
      the results derived from the single-locus analysis, haplotype analysis revealed
      that the haplotype carrying the Thr147 allele was associated with increased risk
      of CHD in France while the reverse tended to hold in the Northern Ireland
      population. Single-locus and haplotype analyses revealed that two polymorphisms,
      C-2599G and Ala147Thr (or T + 1583A that is in nearly complete association with
      it), had additive effects on TAFI levels and explained >18% of TAFI variability.
      This effect was homogeneous in France and Northern Ireland, and in cases and
      controls who exhibited similar TAFI levels. CONCLUSIONS: Thrombin-activatable
      fibrinolysis inhibitor gene polymorphisms are strongly associated to plasma TAFI
      levels, but the relation to CHD risk is less clear.

PMID- 15978109
TI  - Platelet glycoprotein I(b)alpha and integrin alpha2 beta1 polymorphisms: gene
      frequencies and linkage disequilibrium in a population diversity panel.
AB  - Genetic variants in the GP1BA and ITGA2 genes have been proposed as potential
      modifiers for arterial vascular disease and bleeding disorders. Since ancestry
      may play an important role in the prevalence of these variants, we sought to
      determine their allele frequency and linkage disequilibrium in a collection of
      1064 DNA samples from 51 ethnic groups. We studied haplotypes of ITGA2 defined by
      single nucleotide substitutions at positions -52, 807, and 1648, and GP1BA
      variants defined by sequence changes in positions -5 (Kozak), 1018 (T145M, HPA-2)
      and 1285 (VNTR A, B, C and D). Frequency of haplotypes of ITGA2 showed
      considerable variation across the different groups, with a higher prevalence of
      the haplotype -52C or T/807C/1648A observed in African compared with caucasian
      and Asian populations. The haplotypes 52C/807T/1648A and -52T/807T/1648A were not
      observed in caucasians or South Americans. While relative frequencies of the
      GP1BA Kozak alleles were comparable across groups, the methionine allele (HPA-2b)
      showed a higher frequency in Africa (0.26) than in the other groups. We also
      observed a high prevalence of the VNTR B allele in the African and Israeli
      populations. Haplotype analysis revealed incomplete linkage disequilibrium
      between the HPA-2 and VNTR alleles. Incorporation of GP1BA variants into the set
      of SNPs already genotyped by the HapMap project disrupted the pre-existing
      haplotype block. These data provide a valuable resource for optimal selection of
      variants best tailored for association studies of vascular disease or bleeding
      disorders when examining individuals of different ancestral origins.

PMID- 15978110
TI  - Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA
      1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction.
AB  - Conflicting results of an association of the human platelet antigen 1b (HPA
      1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the
      alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis
      and myocardial infarction have been reported. Both platelet receptor
      polymorphisms were genotyped in 3261 patients who had undergone coronary
      angiography, including 1175 survivors of a myocardial infarction, 1211
      individuals with coronary artery disease but no history of myocardial infarction,
      and 571 control patients without angiographic coronary artery disease, and in 793
      blood donors. In a case-control design, the prevalence of HPA-1b and
      alpha(2)807TT genotypes did not differ significantly between the patient groups
      with coronary artery disease or myocardial infarction and patient controls or
      blood donors. By contrast, using a multivariate case-only design, it was found
      that the median age of onset of myocardial infarction was 5.2 years earlier (P =
      0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in
      carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial
      infarction of recent onset with one- or two-vessel coronary artery disease. A
      significant interaction with the conventional risk factors hypercholesterolemia,
      smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human
      platelet antigen 1b and alpha(2)807TT are associated with premature myocardial
      infarction but not with coronary artery disease, suggesting a role of distinct
      integrin genotypes for increased platelet thrombogenicity. This association
      requires confirmation in follow-up studies.

PMID- 15978111
TI  - Stability of full-length recombinant FVIII formulated with sucrose during
      continuous infusion using a mini-pump infusion device.

PMID- 15978112
TI  - The prognostic value of the D-dimer test in cancer patients treated with and
      without low-molecular-weight heparin.

PMID- 15978113
TI  - A vitamin K epoxide reductase complex subunit-1 (VKORC1) mutation in a patient
      with vitamin K antagonist resistance.

PMID- 15978114
TI  - Genetic variation at the estrogen receptor alpha locus in relation to venous
      thromboembolism risk among postmenopausal women.

PMID- 15978115
TI  - Scanning electron microscopical observations of two novel hemostatic polymers.

PMID- 15978116
TI  - Long-haul flights do not activate hemostasis in young healthy men.

PMID- 15978117
TI  - Leukemia and P32 radionuclide synovectomy for hemophilic arthropathy.

PMID- 15978118
TI  - A reconsideration of the evidence for structural reorganization in FVII zymogen.

PMID- 15978119
TI  - Vitamin D analogs down-regulate plasminogen activator inhibitor-1 in human
      coronary artery smooth muscle cells.

PMID- 15978120
TI  - More on: uncertain times for research on hemophilia and allied disorders.

PMID- 15978121
TI  - More on: the biphasic waveform in plasma: identifying the sepsis-coagulation
      crossroad?

PMID- 15978122
TI  - More on: thrombosis and ELISA optical density values in hospitalized patients
      with heparin-induced thrombocytopenia.

PMID- 15978123
TI  - The safety of dosing dalteparin based on actual body weight for the treatment of
      acute venous thromboembolism in obese patients: a rebuttal.

PMID- 15978124
TI  - Genetic structure in four West African population groups.
AB  - BACKGROUND: Africa contains the most genetically divergent group of continental
      populations and several studies have reported that African populations show a
      high degree of population stratification. In this regard, it is important to
      investigate the potential for population genetic structure or stratification in
      genetic epidemiology studies involving multiple African populations. The
      presences of genetic sub-structure, if not properly accounted for, have been
      reported to lead to spurious association between a putative risk allele and a
      disease. Within the context of the Africa America Diabetes Mellitus (AADM) Study
      (a genetic epidemiologic study of type 2 diabetes mellitus in West Africa), we
      have investigated population structure or stratification in four ethnic groups in
      two countries (Akan and Gaa-Adangbe from Ghana, Yoruba and Igbo from Nigeria)
      using data from 372 autosomal microsatellite loci typed in 493 unrelated persons
      (986 chromosomes). RESULTS: There was no significant population genetic structure
      in the overall sample. The smallest probability is associated with an inferred
      cluster of 1 and little of the posterior probability is associated with a higher
      number of inferred clusters. The distribution of members of the sample to
      inferred clusters is consistent with this finding; roughly the same proportion of
      individuals from each group is assigned to each cluster with little variation
      between the ethnic groups. Analysis of molecular variance (AMOVA) showed that the
      between-population component of genetic variance is less than 0.1% in contrast to
      99.91% for the within population component. Pair-wise genetic distances between
      the four ethnic groups were also very similar. Nonetheless, the small between
      population genetic variance was sufficient to distinguish the two Ghanaian groups
      from the two Nigerian groups. CONCLUSION: There was little evidence for
      significant population substructure in the four major West African ethnic groups
      represented in the AADM study sample. Ethnicity apparently did not introduce
      differential allele frequencies that may affect analysis and interpretation of
      linkage and association studies. These findings, although not entirely surprising
      given the geographical proximity of these groups, provide important insights into
      the genetic relationships between the ethnic groups studied and confirm previous
      results that showed close genetic relationship between most studied West African
      groups.

PMID- 15978125
TI  - Predicting transcription factor activities from combined analysis of microarray
      and ChIP data: a partial least squares approach.
AB  - BACKGROUND: The study of the network between transcription factors and their
      targets is important for understanding the complex regulatory mechanisms in a
      cell. Unfortunately, with standard microarray experiments it is not possible to
      measure the transcription factor activities (TFAs) directly, as their own
      transcription levels are subject to post-translational modifications. RESULTS:
      Here we propose a statistical approach based on partial least squares (PLS)
      regression to infer the true TFAs from a combination of mRNA expression and DNA
      protein binding measurements. This method is also statistically sound for small
      samples and allows the detection of functional interactions among the
      transcription factors via the notion of "meta"-transcription factors. In
      addition, it enables false positives to be identified in ChIP data and activation
      and suppression activities to be distinguished. CONCLUSION: The proposed method
      performs very well both for simulated data and for real expression and ChIP data
      from yeast and E. Coli experiments. It overcomes the limitations of previously
      used approaches to estimating TFAs. The estimated profiles may also serve as
      input for further studies, such as tests of periodicity or differential
      regulation. An R package "plsgenomics" implementing the proposed methods is
      available for download from the CRAN archive.

PMID- 15978126
TI  - Do medical outpatients want 'out of hours' clinics?
AB  - BACKGROUND: Patient choice is a major theme in current healthcare delivery.
      Little is known about patients' wishes regarding the timing of medical outpatient
      clinics. METHODS: A questionnaire survey of 300 sequential patients attending
      cardiac and respiratory clinics to determine patients preferences for out of
      hours and weekend outpatient clinics. (Out of hours defined as a clinic after 5
      pm on Mon - Fri) RESULTS: Two hundred and 64 patients completed the survey of
      which 165 (62.5%) wanted either an out of hours clinics or a weekend clinic.
      Sixty four (38.8%) specifically stated that this was because of work commitments
      but for many others, the reasons given were easy to justify. CONCLUSION: Current
      provision for outpatient consultation may not be convenient for many patients
      with heart and lung disease. A fuller evaluation of the cost and benefits of more
      flexible clinic hours is now needed.

PMID- 15978128
TI  - Transhiatal and transthoracic resection in adenocarcinoma of the esophagus: does
      the operative approach have an influence on the long-term prognosis?
AB  - BACKGROUND: The goal of the present analysis was to investigate the long-term
      prognosis for adenocarcinoma of the esophagus treated with either the transhiatal
      (TH) or the transthoracic (TT) operative approach. METHODS: Between September
      1985 and March 2004, esophageal resection due to carcinoma was performed on a
      total of 424 patients. This manuscript takes into account the 150 patients
      suffering from adenocarcinoma of the esophagus in whom a transhiatal resection of
      the esophagus was performed. In the event of transmural tumor growth and a
      justifiable risk of surgery, the transthoracic resection was selected. An
      extended mediastinal lymph node dissection, however, was only carried out in the
      course of the transthoracic approach. RESULTS: The transthoracic resection of the
      esophagus demonstrated a higher rate of general complications (p = 0.011) as well
      as a higher mortality rate (p = 0.011). The mediastinal dissection of the lymph
      nodes, however, revealed no prognostic influence. Considering all of the 150
      patients with adenocarcinoma, as well as only those patients who had undergone
      curative resections (R0), the transhiatal approach was seen to demonstrate a
      better five-year survival rate of 32.1% versus 35.1%, with a median survival time
      of 24 versus 28 months, as compared with those who had undergone a transthoracic
      approach with a five-year survival rate of 13.6% (all patients) versus 17.7% (R0
      resection) with a median survival time of 16 versus 17 months (p < 0.05).
      CONCLUSION: The prognosis in patients with adenocarcinoma of the esophagus is
      influenced by the depth of the tumor (pT) and the pM-category, as shown in the
      multivariate analysis. The present analysis did not demonstrate a relevant
      difference in survival for patients with N0 and N1 stages undergoing transhiatal
      or transthoracic esophagectomy. It is questionable, if a more extensive
      mediastinal lymph node dissection, in addition to the clearance of abdominal
      lymph nodes, offers prognostic advantages in adenocarcinoma of the esophagus.
      However, the morbidity and mortality associated with the transthoracic approach
      is higher.

PMID- 15978127
TI  - Standardization of cytokine flow cytometry assays.
AB  - BACKGROUND: Cytokine flow cytometry (CFC) or intracellular cytokine staining
      (ICS) can quantitate antigen-specific T cell responses in settings such as
      experimental vaccination. Standardization of ICS among laboratories performing
      vaccine studies would provide a common platform by which to compare the
      immunogenicity of different vaccine candidates across multiple international
      organizations conducting clinical trials. As such, a study was carried out among
      several laboratories involved in HIV clinical trials, to define the inter-lab
      precision of ICS using various sample types, and using a common protocol for each
      experiment (see additional files online). RESULTS: Three sample types (activated,
      fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC) were
      shipped to various sites, where ICS assays using cytomegalovirus (CMV) pp65
      peptide mix or control antigens were performed in parallel in 96-well plates. For
      one experiment, antigens and antibody cocktails were lyophilised into 96-well
      plates to simplify and standardize the assay setup. Results ((CD4+)cytokine+
      cells and (CD8+)cytokine+ cells) were determined by each site. Raw data were also
      sent to a central site for batch analysis with a dynamic gating template. Mean
      inter-laboratory coefficient of variation (C.V.) ranged from 17-44% depending
      upon the sample type and analysis method. Cryopreserved peripheral blood
      mononuclear cells (PBMC) yielded lower inter-lab C.V.'s than whole blood.
      Centralized analysis (using a dynamic gating template) reduced the inter-lab C.V.
      by 5-20%, depending upon the experiment. The inter-lab C.V. was lowest (18-24%)
      for samples with a mean of > 0.5% IFNgamma + T cells, and highest (57-82%) for
      samples with a mean of < 0.1% IFNgamma + cells. CONCLUSION: ICS assays can be
      performed by multiple laboratories using a common protocol with good inter
      laboratory precision, which improves as the frequency of responding cells
      increases. Cryopreserved PBMC may yield slightly more consistent results than
      shipped whole blood. Analysis, particularly gating, is a significant source of
      variability, and can be reduced by centralized analysis and/or use of a
      standardized dynamic gating template. Use of pre-aliquoted lyophilized reagents
      for stimulation and staining can provide further standardization to these assays.

PMID- 15978130
TI  - Health information generation and utilization for informed decision-making in
      equitable health service management: the case of Kenya Partnership for Health
      program.
AB  - CONTEXT: The Kenya Partnership for Health (KPH) program began in 1999, and is
      currently one of the 12 field projects participating in the WHO's 'Towards Unity
      for Health initiative' implemented to develop partnership synergies in support of
      the Primary Health Care (PHC) approach 1. CONTENT: This paper illustrates how
      Program-linked Information Management by Integrative-participatory Research
      Approach (PIMIRA) as practised under KPH has been implemented within Trans-Nzoia
      District, Kenya to enhance community-based health initiatives. It shows how this
      model is strategically being scaled-up from one community to another in the
      management of political, social, cultural and economic determinants (barriers and
      enhancers) of health. OBJECTIVE: Target rural communities in the development of a
      community-based health information management and feedback initiatives that can
      provide insights on the social, cultural, political and economic determinants of
      health for utilization in informed health service management. KEY FINDINGS AND
      ACHIEVEMENTS: 1. Cues for health seeking and health service utilization are
      determined by the social, cultural, political and economic factors as seen by the
      individual and as defined by the community but not due to the pathological nature
      of the illness. 2. Establishment of community-based health surveillance and
      health action initiatives as the best practices in transferring health as a
      resource that can be 'owned and guarded' by the community. 3. Establishment of
      Healthy Villages Initiative (HVI) through which health service delivery and scale
      up can be sustained at the community level. 4. Provision of actionable health
      information necessary for health planning and evaluation of preventive health
      programs thorough PIMIRA. CONCLUSION: It has been realized that for every one
      person who visits a health facility for medication, there are nine others who had
      the same condition but sought health care from other sources including self
      medication and five others who never sought health care. Innovative means of
      involving the community in health information management and utilization such as
      PIMIRA are hence the best ways of guaranteeing equitable delivery of health
      services that are accessible and sustainable by the community.

PMID- 15978129
TI  - Th1/Th2 cytokine pattern in bronchoalveolar lavage fluid and induced sputum in
      pulmonary sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is thought to be a T-helper type 1 cytokine (Th2
      cytokine) mediated disorder. Induced sputum (IS) has been proposed as a useful
      non-invasive method, mainly for the assessment of the airway diseases. The aim of
      this study was to explore induced sputum (IS) CD4+ Th1 T-lymphocyte subpopulation
      and to compare them with those of bronchoalveolar lavage fluid (BALF) in patients
      with sarcoidosis. METHODS: We studied prospectively 21 patients (12 female, 9
      male) of median age 46 yr (range, 25-65) with sarcoidosis and 10 normal subjects
      (5 female, 5 male) of median age 39 yr (range, 26-60). IS was performed with
      hypertonic saline solution using an ultrasonic nebulizer. BALF was performed
      within 10 days of IS. After stimulation of sputum lymphocytes with phorbol
      myristate-acetate, we used double immunocytochemical methods to identify CD4+ IFN
      gamma positive and IL-4 positive cells (Th1 and Th2, respectively). RESULTS:
      Sarcoidosis patients had an increased number of CD4+ -IFN-gamma producing cells
      in IS (p = 0.003) and BALF (p = 0.01) in comparison with normal subjects. No
      significant differences were detected between CD4+ -IL-4 cells in BALF (p =
      0.053, NS) and IS (p = 0.46, NS) between sarcoidosis patients and healthy
      controls. The ratio of Th1 to Th2 cells in BALF and IS was statistically
      different in sarcoidosis when compared with normal subjects (p = 0.007 in BALF
      and IS). A significant correlation was found between CD4+ IFN-gamma positive
      cells in IS and those in BALF in sarcoidosis patients (r = 0.685, p = 0.0006).
      CONCLUSION: These data suggests that a Th1-like cytokine pattern can be observed
      in CD4+ T-lymphocytes in IS in patients with pulmonary sarcoidosis. Further
      studies are needed to explore the value of IS vs BALF in the follow-up of these
      patients.

PMID- 15978131
TI  - Bacillus thuringiensis Cry1Ca-resistant Spodoptera exigua lacks expression of one
      of four Aminopeptidase N genes.
AB  - BACKGROUND: Insecticidal toxins from Bacillus thuringiensis bind to receptors on
      midgut epithelial cells of susceptible insect larvae. Aminopeptidases N (APNs)
      from several insect species have been shown to be putative receptors for these
      toxins. Here we report the cloning and expression analysis of four APN cDNAs from
      Spodoptera exigua. RESULTS: Suppression Subtractive Hybridization (SSH) was used
      to construct cDNA libraries of genes that are up-and down-regulated in the midgut
      of last instar larvae of beet armyworm, S. exigua exposed to B. thuringiensis
      Cry1Ca toxin. Among the clones from the SSH libraries, cDNA fragments coding for
      two different APNs were obtained (APN2 and APN4). A similar procedure was
      employed to compare mRNA differences between susceptible and Cry1Ca resistant S.
      exigua. Among the clones from this last comparison, cDNA fragments belonging to a
      third APN (APN1) were detected. Using sequences obtained from the three APN cDNA
      fragments and degenerate primers for a fourth APN (APN3), the full length
      sequences of four S. exigua APN cDNAs were obtained. Northern blot analysis of
      expression of the four APNs showed complete absence of APN1 expression in the
      resistant insects, while the other three APNs showed similar expression levels in
      the resistant and susceptible insects. CONCLUSION: We have cloned and
      characterized four different midgut APN cDNAs from S. exigua. Expression analysis
      revealed the lack of expression of one of these APNs in the larvae of a Cry1Ca
      resistant colony. Combined with previous evidence that shows the importance of
      APN in the mode of action of B. thuringiensis toxins, these results suggest that
      the lack of APN1 expression plays a role in the resistance to Cry1Ca in this S.
      exigua colony.

PMID- 15978132
TI  - Tetrandrine and thapsigargin release arachidonic acid from cells in culture and
      stimulate prostacyclin production in rat liver cells, but may do so by different
      pathways.
AB  - BACKGROUND: Tetrandrine inhibits tumor cell proliferation and demonstrates
      chemoprevention in cancer models. Speculation on the association between its
      effects on K+ and Ca2+ channels and cancer chemoprevention has been made.
      Thapsigargin also affects K+ and Ca2+ conductance. Thapsigargin, however, is a
      weak tumor promoter in the two-stage model of mouse skin carcinogenesis, yet it
      can induce apoptosis in androgen-independent prostatic cancer cells. I have
      postulated that arachidonic acid release from cells in culture is associated with
      cancer chemoprevention. The effects of tetrandrine and thapsigargin on
      arachidonic acid release from human colon carcinoma and rat liver cells and
      prostacyclin production by rat liver cells are compared in the current studies.
      RESULTS: Tetrandrine and thapsigargin stimulate arachidonic acid release from
      human colon carcinoma and rat liver cells and prostacyclin production in rat
      liver cells. The stimulation by tetrandrine is not affected by incubation with
      actinomycin D, 100 mM KCl, the [Ca2+]i chelator, 1,2-bis (o-amino-5
      fluorophenoxy) ethane-N,N,N',N',-tetraacetic acid tetraacetoxymethylester
      (BAPTA/AM) or in the absence of extracellular Ca2+. In contrast, stimulation by
      thapsigargin is inhibited by incubation with actinomycin D, 100 mM KCl, BAPTA/AM
      or in the absence of extracellular Ca2+. CONCLUSION: Both tetrandrine and
      thapsigargin stimulate arachidonic acid release, but based on the different
      results obtained in the presence of actinomycin D, the [Ca2+]i chelator, 100 mM
      KCl and in the absence of extracellular Ca2+, the mechanisms leading to this
      release and pathways leading to apoptosis and/or cancer chemoprevention may be
      different. Stimulations by tetrandrine may be mediated by activation of a
      secretory phospholipase A2, whereas thapsigargin's stimulations may be mediated
      by the cytoplasmic Ca2+-dependent phospholipase A2.

PMID- 15978134
TI  - The management of large perforations of duodenal ulcers.
AB  - BACKGROUND: Duodenal ulcer perforations are a common surgical emergency, but
      literature is silent on the exact definition, incidence, management and
      complications of large perforations of duodenal ulcers. METHODS: The case files
      of 162 patients who underwent emergency laparotomy for duodenal ulcer
      perforations over a period of three years (2001 - 2003) were retrospectively
      reviewed and sorted into groups based on the size of the perforations - one group
      was defined as 'small 'perforations (less than 1 cm in diameter), another 'large'
      (when the perforation was more than 1 cm but less than 3 cms), and the third,
      'giant'(when the perforation exceeded 3 cm). These groups of patients were then
      compared with each other in regard to the patient particulars, duration of
      symptoms, surgery performed and the outcome. RESULTS: A total of 40 patients were
      identified to have duodenal ulcer perforations more than 1 cm in size, thus
      accounting for nearly 25 % of all duodenal ulcer perforations operated during
      this period. These patients had a significantly higher incidence of leak,
      morbidity and mortality when compared to those with smaller perforations.
      CONCLUSION: There are three distinct types of perforations of duodenal ulcers
      that are encountered in clinical practice. The first, are the 'small'
      perforations that are easy to manage and have low morbidity and mortality. The
      second are the 'large' perforations, that are also not uncommon, and omental
      patch closure gives the best results even in this subset of patients. The word
      'giant' should be reserved for perforations that exceed 3 cms in diameter, and
      these are extremely uncommon.

PMID- 15978133
TI  - Immunization of mice with YscF provides protection from Yersinia pestis
      infections.
AB  - BACKGROUND: Yersinia pestis, the causative agent of plague, is a pathogen with a
      tremendous ability to cause harm and panic in populations. Due to the severity of
      plague and its potential for use as a bioweapon, better preventatives and
      therapeutics for plague are desirable. Subunit vaccines directed against the F1
      capsular antigen and the V antigen (also known as LcrV) of Y. pestis are under
      development. However, these new vaccine formulations have some possible
      limitations. The F1 antigen is not required for full virulence of Y. pestis and
      LcrV has a demonstrated immunosuppressive effect. These limitations could damper
      the ability of F1/LcrV based vaccines to protect against F1-minus Y. pestis
      strains and could lead to a high rate of undesired side effects in vaccinated
      populations. For these reasons, the use of other antigens in a plague vaccine
      formulation may be advantageous. RESULTS: Desired features in vaccine candidates
      would be antigens that are conserved, essential for virulence and accessible to
      circulating antibody. Several of the proteins required for the construction or
      function of the type III secretion system (TTSS) complex could be ideal
      contenders to meet the desired features of a vaccine candidate. Accordingly, the
      TTSS needle complex protein, YscF, was selected to investigate its potential as a
      protective antigen. In this study we describe the overexpression, purification
      and use of YscF as a protective antigen. YscF immunization triggers a robust
      antibody response to YscF and that antibody response is able to afford
      significant protection to immunized mice following challenge with Y. pestis.
      Additionally, evidence is presented that suggests antibody to YscF is likely not
      protective by blocking the activity of the TTSS. CONCLUSION: In this study we
      investigated YscF, a surface-expressed protein of the Yersinia pestis type III
      secretion complex, as a protective antigen against experimental plague infection.
      Immunization of mice with YscF resulted in a high anti-YscF titer and provided
      protection against i.v. challenge with Y. pestis. This is the first report to our
      knowledge utilizing a conserved protein from the type III secretion complex of a
      gram-negative pathogen as a candidate for vaccine development.

PMID- 15978135
TI  - Immunomodulatory intervention in sepsis by multidrug-resistant Pseudomonas
      aeruginosa with thalidomide: an experimental study.
AB  - BACKGROUND: Thalidomide is an inhibitor of tumour necrosis factor-alpha
      (TNFalpha) that has been proven effective for the treatment of experimental
      sepsis by Escherichia coli. It was tested whether it might behave as an effective
      immunomodulator in experimental sepsis by multidrug-resistant (MDR) Pseudomonas
      aeruginosa. METHODS: Sepsis was induced by the intraperitoneal injection of 1 x
      10(8) cfu/kg inoculum of the test isolate in a total of 10(9) Wistar rats divided
      in three groups as follows: group A controls; group B administered seed oil 30
      minutes before bacterial challenge; and group C administered 50 mg/kg of
      thalidomide diluted in seed oil 30 minutes before bacterial challenge. Blood was
      sampled for estimation of endotoxins (LPS), TNFalpha, interferon-gamma
      (IFNgamma), nitric oxide (NO) and malondialdehyde (MDA). LPS was measured by the
      QCL-1000 LAL assay, TNFalpha and IFNgamma by ELISA, NO by a colorimetric assay
      and MDA by the thiobarbiturate assay. RESULTS: Mean (+/- SE) survival of groups
      A, B and C were 18.60 +/- 1.84, 12.60 +/- 0.60 and 30.50 +/- 6.62 hours (p of
      comparisons A to C equal to 0.043 and B to C equal to 0.002). Decreased TNFalpha
      and NO levels were found in sera of animals of group C compared to group A.
      Plasma levels of LPS, MDA and IFNgamma did not differ between groups. CONCLUSION:
      Intake of thalidomide considerably prolonged survival in experimental sepsis by
      MDR P. aeruginosa an effect probably attributed to decrease of serum TNFalpha.

PMID- 15978136
TI  - Top 10 health care ethics challenges facing the public: views of Toronto
      bioethicists.
AB  - BACKGROUND: There are numerous ethical challenges that can impact patients and
      families in the health care setting. This paper reports on the results of a study
      conducted with a panel of clinical bioethicists in Toronto, Ontario, Canada, the
      purpose of which was to identify the top ethical challenges facing patients and
      their families in health care. A modified Delphi study was conducted with twelve
      clinical bioethicist members of the Clinical Ethics Group of the University of
      Toronto Joint Centre for Bioethics. The panel was asked the question, what do you
      think are the top ten ethical challenges that Canadians may face in health care?
      The panel was asked to rank the top ten ethical challenges throughout the Delphi
      process and consensus was reached after three rounds. DISCUSSION: The top
      challenge ranked by the group was disagreement between patients/families and
      health care professionals about treatment decisions. The second highest ranked
      challenge was waiting lists. The third ranked challenge was access to needed
      resources for the aged, chronically ill, and mentally ill. SUMMARY: Although many
      of the challenges listed by the panel have received significant public attention,
      there has been very little attention paid to the top ranked challenge. We propose
      several steps that can be taken to help address this key challenge.

PMID- 15978137
TI  - Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of
      expression and correlation with clinical outcome.
AB  - Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and
      Epstein-Barr virus infection has been reported to be a cause of this disease.
      Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly
      expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF
      1), exhibited high expression in organs in which breast cancer metastases are
      often found. The metastatic pattern of NPC is quite similar to that of malignant
      breast tumors. In this study, we investigated the expression of CXCR4 in
      nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different
      staining patterns, which included localization in the nucleus, membrane,
      cytoplasm or a combination of them. The staining intensity was also variable
      among samples. The metastatic rates in patients with high compared to low or
      absent expression was 38.6% versus 19.8%, respectively (P = 0.004). High
      expression of CXCR4 was associated with poor overall survival (OS = 67.05% versus
      82.08%, P = 0.0225). These results suggest that CXCR4 may be involved in the
      progression of NPC and that a high level of CXCR4 expression could be used as a
      prognostic factor.

PMID- 15978139
TI  - Patient-initiated switching between private and public inpatient hospitalisation
      in Western Australia 1980 - 2001: an analysis using linked data.
AB  - BACKGROUND: The aim of the study was to identify any distinct behavioural
      patterns in switching between public and privately insured payment
      classifications between successive episodes of inpatient care within Western
      Australia between 1980 and 2001 using a novel 'couplet' method of analysing
      longitudinal data. METHODS: The WA Data Linkage System was used to extract all
      hospital morbidity records from 1980 to 2001. For each individual, episodes of
      hospitalisation were paired into couplets, which were classified according to the
      sequential combination of public and privately insured episodes. Behavioural
      patterns were analysed using the mean intra-couplet interval and proportion of
      discordant couplets in each year. RESULTS: Discordant couplets were consistently
      associated with the longest intra-couplet intervals (ratio to the average annual
      mean interval being 1.35), while the shortest intra-couplet intervals were
      associated with public concordant couplets (0.5). Overall, privately insured
      patients were more likely to switch payment classification at their next
      admission compared with public patients (the average rate of loss across all age
      groups being 0.55% and 2.16% respectively). The rate of loss from the privately
      insured payment classification was inversely associated with time between
      episodes (2.49% for intervals of 0 to 13 years and 0.83% for intervals of 14 to
      21 years). In all age groups, the average rate of loss from the privately insured
      payment classification was greater between 1981 and 1990 compared with that
      between 1991 and 2001 (3.45% and 3.10% per year respectively). CONCLUSION: A
      small but statistically significant reduction in rate of switching away from PHI
      over the latter period of observation indicated that health care policies
      encouraging uptake of PHI implemented in the 1990s by the federal government had
      some of their intended impact on behaviour.

PMID- 15978138
TI  - Distribution of immunodeficiency fact files with XML--from Web to WAP.
AB  - BACKGROUND: Although biomedical information is growing rapidly, it is difficult
      to find and retrieve validated data especially for rare hereditary diseases.
      There is an increased need for services capable of integrating and validating
      information as well as proving it in a logically organized structure. A XML-based
      language enables creation of open source databases for storage, maintenance and
      delivery for different platforms. METHODS: Here we present a new data model
      called fact file and an XML-based specification Inherited Disease Markup Language
      (IDML), that were developed to facilitate disease information integration,
      storage and exchange. The data model was applied to primary immunodeficiencies,
      but it can be used for any hereditary disease. Fact files integrate biomedical,
      genetic and clinical information related to hereditary diseases. RESULTS: IDML
      and fact files were used to build a comprehensive Web and WAP accessible
      knowledge base ImmunoDeficiency Resource (IDR) available at
      http://bioinf.uta.fi/idr/. A fact file is a user oriented user interface, which
      serves as a starting point to explore information on hereditary diseases.
      CONCLUSION: The IDML enables the seamless integration and presentation of genetic
      and disease information resources in the Internet. IDML can be used to build
      information services for all kinds of inherited diseases. The open source
      specification and related programs are available at http://bioinf.uta.fi/idml/.

PMID- 15978140
TI  - Prostate-Specific Antigen Modulates the Expression of Genes Involved in Prostate
      Tumor Growth.

PMID- 15978141
TI  - Bariatric surgery: Asia-Pacific perspective.
AB  - BACKGROUND: There is a world-wide epidemic of overweight, obesity and morbid
      obesity. Bariatric surgery today, as the only effective therapy for morbid
      obesity, is expanding exponentially to meet the global epidemic of morbid
      obesity. Bariatric surgeons in the Asia-Pacific region had founded the Asia
      Pacific Bariatric Surgery Group (APBSG) at Seoul, Korea on October 6, 2004.
      METHODS: E-mail requests for information were sent to the national bariatric
      surgery leaders. These requests were followed, if necessary, by second e-mail
      requests and communications seeking clarification. The summary data was also
      discussed at the 1st Asia-Pacific Bariatric Consensus Meeting held in Taipei,
      February 27, 2005. RESULTS: 11 countries or areas in Asia had started bariatric
      surgery and responded to the general questions. In 2004, 636 bariatric operations
      were performed by 61 bariatric surgeons. The earliest data for starting bariatric
      surgery was in 1974 in Taiwan. Following the development of gastric partition,
      Taiwan performed the first case in 1981, Japan in 1982 and Singapore in 1987. In
      2004, 11 countries have started bariatric surgery. The APBSG was founded in 2004.
      In 2004, 12.1% of operations were open and 87.9% laparoscopic. The 6 most popular
      operations were: laparoscopic adjustable banding 42.3%; laparoscopic gastric
      bypass 34.2%; open vertical banded gastroplasty 7.5%; laparoscopic vertical
      banded gastroplasty 6.3%; laparoscopic sleeve gastrectomy 6.3%; open gastric
      bypass 4.2%. Pooling open and laparoscopic procedures, relative percentages were
      gastric banding 42.3%; gastric bypass 38.4%; vertical banded gastroplasty 13.8%.
      The APBSG consensus meeting recommended bariatric surgery in Asian patients with
      BMI >37 or >32 with diabetes or two other obesity-related co-morbidities.
      CONCLUSIONS: Bariatric surgery is expanding rapidly in Asia to meet rapidly
      increasing obesity. The modification of the indications for bariatric surgery in
      the Asian is proposed.

PMID- 15978142
TI  - Obesity-related differential gene expression in the visceral adipose tissue.
AB  - BACKGROUND: This study investigates the expression patterns in human adipose
      tissue, and identifies genes that may be involved in the abnormal energy
      homeostasis. METHODS: Subjects were prospectively recruited from morbidly obese
      patients undergoing bariatric surgery and from non-obese organ donors. Extensive
      clinical data and visceral fat specimens were obtained from each subject at the
      time of surgery. A group of 50 obese patients and 9 non-obese controls were
      selected for further study. Two custom two-color cDNA microarrays were produced
      with 40,173 human individual cDNA clones. Microarray experiments were performed
      for each sample, and a selected group of gene expression values were confirmed
      with real-time RT-PCR. RESULTS: A comparison of gene expression profiles from
      obese and non-obese patients identified 1,208 genes with statistically
      significant differential expression between the 2 groups. Most prominent among
      these genes are multiple glycolysis enzyme encoding genes; others are involved in
      oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute
      carriers. CONCLUSION: Differential gene expression in the adipose tissue of
      morbidly obese patients includes genes related to lipid and glucose metabolism,
      membrane transport, and genes promoting the cell cycle. These findings are a
      first step toward clarifying the molecular pathogenesis of obesity and
      identifying potential targets for therapeutic intervention.

PMID- 15978143
TI  - The orientation of the antecolic Roux limb markedly affects the incidence of
      internal hernias after laparoscopic gastric bypass.
AB  - BACKGROUND: Internal herniation of the bowel may be a late complication after the
      laparoscopic Roux-en-Y gastric bypass (RYGBP). A seemingly minor change in
      technique is described that significantly prevents herniation behind the Roux
      limb mesentery. We hypothesized that internal hernias behind the Roux limb
      mesentery occur more frequently when the Roux limb is oriented such that the
      distal tip is toward the lesser curvature of the gastric pouch with the bowel
      then curving to the patient's left, compared with the opposite orientation.
      METHODS: A retrospective chart review was performed of our prospectively
      collected database. A change in surgical technique occurred June 2003, in an
      attempt to reduce internal hernia formation. We compared 200 consecutive
      antecolic left-oriented RYGBP operations performed immediately previous to June
      2003 (Group A) with 200 consecutive antecolic right-oriented RYGBP operations
      performed after June 2003 (Group B). RESULTS: There was an 9.0% rate of internal
      hernia formation in Group A (18/200) and a 0.5% rate of internal hernia formation
      in Group B. Internal hernias were repaired an average of 1.2 years after surgery
      (range 4-30 months, median 14.3 months). The average length of follow-up was 2.1
      and 1.6 years in Groups A and B, respectively. All herniations were behind the
      Roux limb mesentery. The difference in hernia formation after the change in
      technique was significant (P<0.005). CONCLUSIONS: With a simple change in
      technique, the incidence of internal herniation behind the Roux limb mesentery
      may be significantly reduced or eliminated.

PMID- 15978145
TI  - The proximal gastric pouch invariably contains acid-producing parietal cells in
      Roux-en-Y gastric bypass.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is well tolerated and effective in
      ameliorating diseases common to morbidly obese patients. A potential drawback,
      however, is the risk for stomal ulcers, probably due to acid and peptic digestion
      of the mucosa in the proximal Roux limb. METHODS: In 23 RYGBP patients (mean BMI
      45 kg/m(2), age 39 years), the gastro-jejunostomy was performed by circular
      stapler and the gastric suture ring retrieved for histological examination. 13
      consecutive patients received our standard totally transected 4 x 3 cm proximal
      gastric pouch. The anvil was passed transgastricly and reference biopsies were
      taken from the gastrotomy in the corpus of the stomach. In the last 10 patients,
      the pouch size was reduced to 2 x 3 cm by a modified surgical technique. RESULTS:
      All suture rings from the standard pouches consisted of corpus-fundus mucosa with
      a large amount of parietal cells, histologically identical to the reference
      biopsies from the gastrotomy. Also, the 10 suture rings from the modified small
      pouches contained corpus-fundus mucosa. In 5 of these samples, cardiac mucosa was
      found, but only in a small segment (6 mm). In addition, 3 patients had esophageal
      epithelium in the suture ring. CONCLUSION: The proximal pouch invariably contains
      acid-producing parietal cells. In order to reduce acid production and, hence, the
      risk of stomal ulcers, the pouch has to be made as small as possible.

PMID- 15978146
TI  - Inpatient pain medication requirements after laparoscopic gastric bypass.
AB  - INTRODUCTION: One of the benefits of laparoscopic Roux-en-Y gastric bypass
      (RYGBP) includes decreased pain, possibly resulting in decreased narcotic use,
      quicker recovery of bowel function, and shorter hospital stay. We utilize a pain
      management strategy for our patients undergoing laparoscopic RYGBP. We
      investigated this strategy as well as narcotic use and incidence of ileus.
      METHODS: Inpatient data for patients who underwent laparoscopic RYGBP were
      collected. Our pain management strategy included a standing dose of ketorolac,
      morphine sulphate as needed, and propoxyphene hydrochloride/acetaminophen as
      needed after liquids were initiated. No PCAs were utilized. RESULTS: There were
      104 patients in this study. 12 patients did not undergo our pain management
      strategy due to reoperation (5), postoperative hemorrhage (2), and allergies (5).
      2 patients required no pain medications other than ketorolac. Only 2 patients had
      a delay of discharge (postoperative day [POD] 3 and 5) due to lack of bowel
      function. An average of 11.2 mg of morphine and an average of 170 mg of
      propoxyphene (1.7 pills) were given by the end of POD 2. In addition, 74% of
      patients required no morphine on POD 2 and 48% of patients required no
      propoxyphene on POD 2. Bowel movements were reported in 65% patients on POD 1.
      CONCLUSIONS: After laparoscopic RYGBP, only a minimal amount of narcotic use is
      necessary. Few patients have an ileus when utilizing this pain management
      strategy after laparoscopic RYGBP.

PMID- 15978147
TI  - Comparison between open hand-sewn, laparoscopic stapled and laparoscopic computer
      mediated, circular stapled gastro-jejunostomies in Roux-en-Y gastric bypass in
      the porcine model.
AB  - BACKGROUND: In this porcine survival model, we compared laparoscopic computer
      mediated flexible circular stapled (SurgASSIST) gastro-jejunostomies in Roux-en-Y
      gastric bypass (RYGBP) to open hand-sewn (HS) and laparoscopic end-to-end (EEA)
      anastomosis. METHODS: RYGBP was performed in 15 pigs. Depending on the technique
      used to create the gastro-jejunostomy, the pigs were divided in 3 groups. In
      group A, a standard two-layer hand-sewn anastomosis were performed. In group B
      and C, gastro-jejunostomies using EEA (B) or SurgASSIST (C) were attempted.
      Operation time, intraoperative technical failure, postoperative anastomotic
      leakage, and necropsy results were measured. RESULTS: 14 pigs survived surgery.
      One leakage from the gastro-jejunostomy was detected intraoperatively in group B.
      There was no evidence of leakage postoperatively from the proximal gastro
      jejunostomy in any groups. No statistical difference was found between the groups
      concerning the operation time or the diameter and degree of healing of the
      anastomosis. CONCLUSION: We found the SurgASSIST system safe for performing
      gastro-jejunostomies in laparoscopic RYGBP. There were no anastomotic failures
      intra- or postoperatively. At necropsy, there was no evidence of anastomotic
      stricture or delayed healing processes.

PMID- 15978148
TI  - Histological behavior of hepatic steatosis in morbidly obese patients after
      weight loss induced by bariatric surgery.
AB  - BACKGROUND: Hepatic steatosis has a high prevalence among morbidly obese
      patients. Its relation to steatohepatitis and cirrhosis has been extensively
      studied among these patients. The aim of this study was to evaluate the behavior
      of hepatic steatosis with weight loss 1 year after bariatric surgery. METHODS:
      This study is a historical cohort that compared liver biopsies obtained from
      morbidly obese patients during the bariatric operation, with percutaneous
      biopsies taken from the same patient 1 year after surgery. The results were
      compared with weight loss, patients' profile (gender, age, body mass index (BMI)
      and waist/hip ratio), and with the presence of co-morbidities such as diabetes,
      hypertension, and dyslipidemia. RESULTS: 90 patients who had liver biopsies taken
      at the operation and postoperative period for bariatric surgery were included.
      The prevalence of hepatic steatosis was 87.6%. The average percent of excess
      weight loss was 81.4%. On the second biopsy, 16 patients (17.8%) of the total had
      the same degree of steatosis, 25 (27.8%) improved their steatosis pattern and 49
      (54.4%) had normal hepatic tissue. There was no statistical difference regarding
      age, BMI, waist/hip ratio, and co-morbidities (P>0.05), but there was a
      difference in gender (P=0.044). CONCLUSION: Significant improvement in the
      hepatic histology of steatosis was observed after weight loss induced by
      bariatric surgery in most patients. There was no patient with a worsening in the
      histology.

PMID- 15978149
TI  - Effects of weight loss after biliopancreatic diversion on metabolism and
      cardiovascular profile.
AB  - BACKGROUND: Obesity is associated with increased prevalence of cardiovascular
      risk factors. Biliopancreatic diversion (BPD) for morbid obesity has been
      reported to produce anemia and malnutrition in short-term follow-up. The aim of
      our study was to analyze the effect of weight reduction on cardiovascular
      profile, renal function and nutritional status. METHODS: 35 morbidly obese
      patients underwent BPD. We analyzed the presence of cardiovascular risk factors,
      renal status, proteinuria and nutritional status before and 1 year after BPD.
      RESULTS: Excess weight loss was 67% at 1 year after BPD. All cardiovascular risk
      factors (hypertension, diabetes, hyperlipidemia) improved during follow-up. We
      could not find any relevant signs of malnutrition in the patients.
      Microalbuminuria decreased and proteinuria disappeared after weight loss. We
      observed less urinary calcium and citrate excretion, with an increase in
      oxaluria, but these changes did not increase the incidence of renal stones.
      CONCLUSIONS: BPD was followed by improved cardiovascular profile and a lower pro
      inflammatory state. BPD did not produce significant malnutrition, anemia or renal
      stone disease.

PMID- 15978150
TI  - Early clinical and surgical results of biliopancreatic diversion.
AB  - BACKGROUND: Scopinaro biliopancreatic diversion (BPD) for morbid obesity results
      in significant longterm weight loss and reduction or resolution of obesity
      associated co-morbidities. The aim of our work was to describe the early results
      after BPD. METHODS: 59 morbidly obese patients (BMI >40) underwent open BPD from
      December 2001 to December 2004. We analyzed a consecutive series of 19 patients
      who have been followed >4 months. We present the data of basal and early visits
      (2 and 4 months). RESULTS: Initial excess weight percent loss (IEW%L) was 5.2% at
      2 months and 13.7% at 4 months. Glycemia, cholesterol, triglyceride levels and
      blood pressure improved at each visit. All parameters have significant
      differences from the basal values. 3 patients had sleep apnea syndrome, and
      overnight CPAP was able to cease in 2 patients by 4 months. 6 patients (31.5%)
      had albumin <2.5 g/dl, without clinical findings of malnutrition. Total calorie
      (857+/-79.8 cal/day) and protein (59.8+/-23 g/day) intakes at 4 months were low,
      with a low intake of multivitamins and oligoelements from food. There was no
      mortality in this series. Early postoperative morbidity was incisional hernia
      (21.1%), anastomotic leak (5.2%), wound infection (15.7%), intra-abdominal
      infection (5.2%), and intestinal obstruction (5.2%). CONCLUSION: BPD showed early
      effectiveness in weight loss and co-morbidity improvement. Calorie, protein,
      oligoelement and vitamin dietary intakes were below recommendations, so that
      strict multidisciplinary follow-up and supplementation to prevent or treat
      nutritional deficiencies are mandatory.

PMID- 15978151
TI  - Serum hepatocyte growth factor concentration in obese women decreases after
      vertical banded gastroplasty.
AB  - BACKGROUND: Human obesity is associated with increased serum hepatocyte growth
      factor (HGF) concentration. This study examines whether reduced body fat mass
      after vertical banded gastroplasty (VBG) is associated with a decrease in serum
      HGF concentration. METHODS: Serum HGF concentration and body weight, BMI, body
      fat mass, blood pressure, serum leptin, insulin, triacylglycerol, and cholesterol
      concentrations were studied in 10 obese women before and 1 year after VBG. 10
      lean, healthy women were used as controls. RESULTS: Obese women showed
      significantly higher serum HGF concentration than control (lean, healthy)
      subjects. The mean serum HGF concentration decreased significantly 1 year after
      VBG, but did not reach the value observed in lean women. After VBG, BMI, body fat
      mass and serum HGF had similar patterns of decrease. Moreover, serum HGF
      concentration was positively correlated with both BMI (r=0.6, P<0.01) and body
      fat mass (r=0.6, P<0.01). Before surgery in obese women, elevated blood pressure
      was observed, which decreased after VBG. Linear regression analysis between blood
      pressure and serum HGF concentration using all subjects, showed no correlation
      between either systolic blood pressure and serum HGF concentration (r=.15, P=NS)
      or between diastolic blood pressure and serum HGF concentration (r=0.1, P=NS).
      Insulin resistance index (HOMA score), serum leptin, insulin and triacylglycerol
      concentrations decreased 1 year after VBG. However, serum cholesterol
      concentration did not change significantly. CONCLUSIONS: These results indicate
      that VBG results in a reduction in circulating HGF concentration. The reduced
      body fat mass may contribute in part to the decrease of serum HGF concentration
      after VBG. Because elevated serum HGF concentration may contribute to the
      progression of atherosclerosis, the decrease in serum HGF concentration after VBG
      may be beneficial for obese subjects.

PMID- 15978152
TI  - Preoperative resting energy expenditure does not predict weight loss and
      maintenance after vertical banded gastroplasty.
AB  - BACKGROUND: The authors evaluated the predictive efficacy of preoperative resting
      energy expenditure (REE) on long-term weight loss maintenance following vertical
      banded gastroplasty (VBG). In the long-term following VBG, low energy expenditure
      could lead to regain of weight, and thereby REE data might be a reliable
      predictor of long-term weight outcomes. METHODS: A prospective study was
      conducted, taking into account the relationship between preoperative REE values
      and the results at 3 and 5 years following VBG in terms of both weight loss and
      success of the operation. RESULTS: Long-term weight loss and outcome following
      VBG appeared to be completely independent of the preoperative REE. CONCLUSION:
      Preoperative REE cannot predict long-term weight outcome following VBG.

PMID- 15978153
TI  - Tissue oxygenation in obese and non-obese patients during laparoscopy.
AB  - BACKGROUND: Wound infection risk is inversely related to subcutaneous tissue
      oxygenation, which is reduced in obese patients and may be reduced even more
      during laparoscopic procedures. METHODS: We evaluated subcutaneous tissue
      oxygenation (PsqO(2)) in 20 patients with a body mass index (BMI) > or=40 kg/m(2)
      (obese group) and 15 patients with BMI <30 kg/m(2) (non-obese group) undergoing
      laparoscopic surgery with standardized anaesthesia technique and fluid
      administration. Arterial oxygen tension was maintained near 150 mmHg. PsqO(2) was
      measured from a surrogate wound on the upper arm. RESULTS: A mean FIO(2) of 51%
      (13%) was required in obese patients to reach an arterial oxygen tension of 150
      mmHg; however, a mean FIO(2) of only 40% (7%) was required to reach the same
      oxygen tension in non-obese patients (P=0.007). PsqO(2) was significantly less in
      obese patients: 41 (10) vs 57 (15) mmHg (P<0.001). CONCLUSION: Obese patients
      having laparoscopic surgery require a significantly greater FIO(2) to reach an
      arterial oxygen tension of about 150 mmHg than non-obese patients; they also have
      significantly lower subcutaneous oxygen tensions. Both factors probably
      contribute to an increased infection risk in obese patients.

PMID- 15978154
TI  - A prospective randomized trial of placement of the laparoscopic adjustable
      gastric band: comparison of the perigastric and pars flaccida pathways.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a safe and
      effective method for the treatment of obesity. The most common problem after LAGB
      has been the occurrence of prolapse (slippage) of the stomach through the band.
      It has been proposed that the pars flaccida (PF) pathway (dissection from the
      base of the right crus, along the left crus to the angle of His) is less likely
      to be associated with prolapse than the traditional perigastric (PG) pathway
      (dissection between the lesser curvature of stomach and lesser omentum, across
      the apex of the lesser sac, to the angle of His). We have tested this hypothesis
      using a randomized controlled trial format. METHODS: We have performed a
      randomized controlled trial to compare the outcomes after LAGB using PF and PG
      pathways. 202 patients (mean age 40 years, mean weight 123 kg, mean BMI 45) were
      randomly allocated to the PF or PG pathway and followed for 2 years. RESULTS: At
      24 months, there have been 16 revisional procedures for prolapse, 4 in the PF
      group (all anterior prolapse) and 15 in the PG group (12 posterior and 3
      anterior). This difference is significant (P<0.001). The mean % excess weight
      lost was 53% for the PF group and 46% for the PG group. There was equally
      significant improvements in the metabolic syndrome in both groups (59%
      preoperatively and 19% at 2 years). All 8 paired domain scores of the SF-36
      measures of quality of life were improved significantly in both group (P<0.001).
      CONCLUSIONS: The PF pathway is as effective as the PG pathway in generating
      substantial weight loss, improved health and improved quality of life and is
      significantly less likely to be associated with prolapse (slippage). It is
      recommended as the primary dissection pathway.

PMID- 15978155
TI  - One-year changes in energy expenditure and serum leptin following adjustable
      gastric banding in obese women.
AB  - BACKGROUND: Weight loss is associated with a decrease in both energy expenditure
      and circulating leptin levels. Whether this holds true when the influence of body
      composition on energy expenditure and leptin is taken into account remains
      controversial. The aim of the study was to assess changes in resting metabolic
      rate (RMR) and serum leptin adjusted for body composition during surgically
      induced weight loss. METHODS: In 36 women (age 42.7+/-8.7 years; BMI 47.2+/-8.5
      kg/m(2); mean+/-SD) undergoing laparoscopic adjustable gastric banding (LAGB) for
      morbid obesity, we measured RMR (by indirect calorimetry), body composition (by
      dual-energy X-ray absorptiometry) and serum leptin (by immunoradiometry),
      immediately before and 1 year after surgery. RESULTS: 1 year after LAGB, there
      were significant decreases in body weight (-23.7+/-11.6 kg, P<0.001), fat mass
      (FM: -20.9+/-11.3 kg, P<0.0001), lean body mass (LBM: -3+/-5.3 kg, P=0.005), RMR
      (-298+/-309 kcal/day, P<0.0001), serum leptin (-24.0+/-18.4 ng/ml, P<0.0001),
      RMR/LBM ratio (-3.9+/-5.8 kcal/kg LBM/day, P<0.01) and leptin/FM ratio (-0.21+/
      0.29 ng/kg FM/ml, P<0.001). RMR values after surgery were correctly predicted by
      the regression equation relating RMR to LBM and FM at baseline, whereas this was
      not the case for serum leptin (in relation to FM). CONCLUSIONS: Changes in RMR 1
      year after LAGB were explained by changes in body composition whereas changes in
      serum leptin were not. The data provide no evidence for a metabolic adaptation of
      RMR with weight loss, but suggest that serum leptin is decreased beyond expected
      values based on body composition, a factor that may favor weight regain after
      surgically induced weight loss.

PMID- 15978156
TI  - Esophageal dilatation after laparoscopic adjustable gastric banding: definition
      and strategy.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has become a method of
      choice worldwide to treat morbid obesity. Long-term complications such as
      esophageal dilatation require that a relevant strategy for treatment be defined.
      Esophageal dysmotility is commonly described in morbidly obese patients. METHODS:
      1,232 patients have undergone LAGB over 9 years (1995-2004), and 162 (13.1%) have
      had a reoperation for complications (excluding access-port problems): slippage
      (109), erosion (28), intolerance (25). 80 patients (6.4%) had their band removed,
      and 10 had a switch to another procedure. Esophageal dilatation has been an
      isolated cause for removal in 2 patients and an associated cause in 6 patients.
      RESULTS: There was no significant correlation between esophageal dilatation and
      insufficient excess weight loss (<25%) after 5 years (37/257:14.3%). 4 stages of
      dilatation were identified, with the relevant treatment for each, the ultimate
      alternative being conversion to a laparoscopic gastric bypass. We suggest that
      esophageal dilatation be a separate issue from pouch dilatation and gastric
      erosion, and that it be classified as a complication only in severe cases
      requiring band removal. Most cases can be handled through deflation of the band
      under radiological control. CONCLUSION: LAGB can lead to significant esophageal
      troubles which must remain under scrutiny but generally respond to "radiological
      management", which also makes LAGB more demanding than other operations in terms
      of follow-up.

PMID- 15978157
TI  - Treatment of intra-gastric band migration following laparoscopic banding: safety
      and feasibility of simultaneous laparoscopic band removal and replacement.
AB  - BACKGROUND: Intra-gastric band migration (band erosion) following laparoscopic
      adjustable gastric banding (LAGB) is a known complication requiring revisional
      surgery. Management has most often involved band removal and suturing of the
      stomach wall, followed by delayed replacement at a third operation. We report our
      experience with simultaneous band removal and replacement. METHODS: Between May
      2001 and December 2003, we performed 754 laparoscopic operations using the Lap
      Band (R). Patients developing band erosion were treated by laparoscopic band
      removal and immediate replacement of a new band following gastric wall repair.
      RESULTS: 16 patients (2.1%) developed band erosion after a mean of 23 months
      following surgery (range 11-40 months). Patients presented with epigastric pain
      (6), port-site bulge (3) or were asymptomatic (7), band erosion being suspected
      during fluoroscopy for band adjustment and confirmed by gastroscopy.
      Postoperatively, 11 patients developed fever that responded to antibiotics. No
      patient suffered from intra-abdominal infection, wound infection, pneumonia or
      pulmonary embolism. Mean hospital stay was 4 days (range 1-8 days). CONCLUSION:
      Band erosion following LAGB can be treated safely with simultaneous laparoscopic
      band removal, gastric wall suturing and immediate replacement of the band,
      thereby preventing weight gain, the appearance of co-morbidities and the need for
      additional surgery.

PMID- 15978158
TI  - Laparoscopic adjustable gastric banding results after 2 years with two different
      band types.
AB  - BACKGROUND: Laparoscopic gastric banding is the most common operation in Europe
      for morbid obesity. Many devices from different companies are now available. The
      aim of this study was to compare the results over a 2-year period of 2 types of
      band: the Lap-Band and the Minimizer band. METHODS: In a non-randomized study, 2
      consecutive groups were prospectively analyzed. Group A consisted of 120 patients
      who received the Lap-Band, and group B consisted of 68 patients who received the
      Minimizer band which contains eyelets. All the bands were placed above the lesser
      sac by the perigastric approach. RESULTS: 4 early complications were observed in
      group A (1 phlebitis, 1 pneumopathy and 2 early displacements of the band); and 1
      in group B (1 retention of urine). After a follow-up of 2 years, the displacement
      rate of the band was 10.8% in group A and 0% in group B. One gastric erosion was
      observed in group B, but not in group A. After 2 years, the average loss of
      excess weight was 50% in both groups. CONCLUSION: With the Minimizer band, we did
      not observe any slipping, and the efficacy with respect to weight loss was
      equivalent to the Lap-Band.

PMID- 15978159
TI  - Laparoscopic bariatric surgery in super-obese patients (BMI>50) is safe and
      effective: a review of 332 patients.
AB  - BACKGROUND: Bariatric surgery in super-obese patients (BMI >50 kg/m(2)) can be
      challenging because of difficulties in exposure of visceral fat, retracting the
      fatty liver, and strong torque applied to instruments, as well as existing co
      morbidities. METHODS: A retrospective review of super-obese patients who
      underwent laparoscopic adjustable gastric banding (LAGB n=192), Roux-en-Y gastric
      bypass (RYGBP n=97), and biliopancreatic diversion with/without duodenal switch
      (BPD n= 43), was performed. 30 day peri-operative morbidity and mortality were
      evaluated to determine relative safety of the 3 operations. RESULTS: From October
      2000 through June 2004, 331 super-obese patients underwent laparoscopic bariatric
      surgery, with mean BMI 55.3 kg/m(2). Patients were aged 42 years (13-72), and 75%
      were female. When categorized by operation (LAGB, RYGBP, BPD), the mean age, BMI
      and gender were comparable. 6 patients were converted to open (1.8%). LAGB had a
      0.5%, RYGBP 2.1% and BPD 7.0% conversion rate (P=0.02, all groups). Median
      operative time was 60 min for LAGB, 130 min for RYGBP and 255 min for BPD
      (P<0.001, all groups). Median length of stay was 24 hours for LAGB, 72 hours for
      RYGBP, and 96 hours for BPD (P <0.001). Mean %EWL for the LAGB was 35.3+/-12.6,
      45.8+/-19.4, and 49.5+/-18.6 with follow-up of 87%, 76% and 72% at 1, 2 and 3
      years, respectively. Mean %EWL for the RYGBP was 57.7+/-15.4, 54.7+/-21.2, and
      56.8+/-21.1 with follow-up of 76%, 33% and 54% at 1, 2 and 3 years, respectively.
      Mean %EWL for the BPD was 60.6+/-15.9, 69.4+/-13.0 and 77.4+/-11.9 with follow-up
      of 79%, 43% and 47% at 1, 2 and 3 years, respectively. The difference in %EWL was
      significant at all time intervals between the LAGB and BPD (P<0.004). However,
      there was no significant difference in %EWL between LAGB and RYGBP at 2 and 3
      years. Overall perioperative morbidity occurred in 27 patients (8.1%). LAGB had
      4.7% morbidity rate, RYGBP 11.3%, and BPD 16.3% (P=0.02, all groups). There were
      no deaths. CONCLUSION: Laparoscopic bariatric surgery is safe in super-obese
      patients. LAGB, the least invasive procedure, resulted in the lowest operative
      times, the lowest conversion rate, the shortest hospital stay and the lowest
      morbidity in this high-risk cohort of patients. Rates of all parameters studied
      increased with increasing procedural complexity. However, the difference in %EWL
      between RYGBP and LAGB at 2 and 3 years was not statistically significant.

PMID- 15978160
TI  - What becomes of patients one year after the intragastric balloon has been
      removed?
AB  - BACKGROUND: The BioEnterics Intragastric Balloon (BIB) is a saline-filled balloon
      recommended to remain in the gastric cavity for a maximum of 6 months. Is this
      short period sufficient to change patients' lifestyle and eating practices to
      maintain weight reduction after BIB removal? METHODS: 100 patients who received a
      BIB were included in this prospective study and followed for 1 year after BIB
      removal. The post-implantation follow-up visits took place monthly, during which
      the patient was seen by the surgeon, dietitian, and if necessary, psychologist.
      RESULTS: At BIB removal, mean weight loss for the group was 12.0 kg. Mean percent
      excess weight loss (%EWL) was 39.8%. 12 months after removal of the BIB, mean
      weight loss was 8.6 kg and mean %EWL was 26.8% for the group as a whole.
      CONCLUSIONS: The results 1 year after removal of the BIB were encouraging.
      Because the BIB is a temporary non-surgical and non-pharmaceutical treatment for
      obesity that is reversible and repeatable, we recommend it to patients who have
      previously failed traditional methods of weight reduction. Careful patient follow
      up is of primary importance in avoiding complications and supporting efficacy of
      the treatment. Although 1 year follow-up cannot be considered long term, these
      results are encouraging. Concurrent behavior modification is needed for durable
      weight loss.

PMID- 15978161
TI  - Application of a trocar wound closure system designed for laparoscopic procedures
      in morbidly obese patients.
AB  - Herniation into the trocar-site is a relatively common complication of
      laparoscopic surgery, and represents a serious cause of morbidity because of the
      potential to develop into a Richter's hernia. The risk of trocar-site herniation
      is greater in obese and bariatric patients, because of the larger preperitoneal
      space and elevated intra-abdominal pressure; thus, fascial closure alone is not
      adequate. Full-thickness trocar-wound closure can prevent this complication.
      However, hand suturing and some port-closure devices can be difficult to use in
      this patient group. We report on the use of a specialized trocar wound closure
      system designed for use on obese and bariatric patients. In this report, we
      describe use of the system in the case of a 34-year-old Caucasian female who
      underwent a laparoscopic Roux-en-Y gastric bypass procedure.

PMID- 15978162
TI  - Prevention of rhabdomyolysis in bariatric surgery.
AB  - BACKGROUND: Rhabdomyolysis (RML) is a clinical and biochemical syndrome caused by
      skeletal muscle necrosis that results in extravasation of toxic intracellular
      contents from the myocytes into the circulatory system. Postoperative RML in
      bariatric surgery occurs with various non-physiological surgical positions, with
      prolonged muscle compression. The potential consequences may lead to death. The
      purpose of this study is to review its pathophysiology and the best ways to
      prevent RML in bariatric surgery. METHODS: We searched the literature and
      reviewed all relevant articles, by searching for the keywords: rhabdomyolysis,
      morbid obesity, prevention and bariatric surgery, giving a total of 39 articles.
      RESULTS: Prevention may be enhanced by careful padding on the operative table at
      all pressure-points. Changing patient position, both intraoperatively and
      postoperatively, also reduces RML. A potential new solution to decrease the
      longer operative time and avoid RML is to perform the bariatric operation in two
      stages. Another way to limit the duration of surgery in high-risk patients is to
      alert surgeons not to select super-obese high-risk patients early in the learning
      curve. CONCLUSION: As RML is an important and potentially fatal complication of
      bariatric surgery, the best way to avoid it is effective prevention. More
      research on this subject is necessary.

PMID- 15978163
TI  - Late perforation of the jejuno-jejunal anastomosis after laparoscopic Roux-en-Y
      gastric bypass.
AB  - Roux-en-Y gastric bypass (RYGBP) is the most commonly performed operation for the
      treatment of morbid obesity in the USA. Complications related to the jejuno
      jejunal (J-J) anastomosis include postoperative leak, staple-line bleeding and
      obstruction. We present 3 cases of perforation at the J-J anastomosis occurring
      more than 30 days after surgery. 3 morbidly obese patients underwent laparoscopic
      RYGBP. The side-to-side J-J anastomosis was created with a linear stapler, and
      the anastomotic defect was closed with a running absorbable suture. All 3
      patients had uneventful recoveries, but presented 7 to 8 weeks postoperatively
      with acute abdominal pain and peritoneal signs. Exploratory laparoscopy in these
      patients revealed a perforation at the J-J anastomosis. No apparent reason for
      the perforation was found in 2 patients. These perforations were repaired
      laparoscopically with absorbable suture. The third patient had an obstruction at
      the J-J anastomosis from an phytobezoar and required conversion to open technique
      due to limited pneumoperitoneum. All 3 patients recovered uneventfully. Late
      perforation of the J-J anastomosis is a very rare complication. Primary
      laparoscopic repair is a feasible and safe choice of treatment.

PMID- 15978164
TI  - Thyrotoxicosis after gastric bypass surgery prompting operative re-exploration.
AB  - In the last 10 years, gastric bypass has become an increasingly common operation
      performed by general surgeons. The complications resulting from this procedure
      can be life-threatening and are often difficult to diagnose, particularly in the
      immediate postoperative period. We detail a case of thyrotoxicosis manifesting on
      postoperative day 1 which presented with symptoms mimicking an anastomotic leak.
      The patient underwent a negative laparoscopy before the thyroid dysfunction was
      diagnosed. There is no evidence that bariatric surgery carries a greater risk of
      postoperative thyrotoxicosis than any other non-thyroid operation. Many of the
      symptoms of thyrotoxicosis, however, are similar to those of other surgery
      related complications, and it should be immediately considered in the
      differential diagnosis of a postoperative bariatric patient with tachycardia and
      fever. Failure to rule out this condition may lead to unnecessary surgery.

PMID- 15978165
TI  - Portal vein thrombosis after laparoscopic gastric bypass.
AB  - Splanchnic vessel thrombosis has been described after several laparoscopic
      operations. However, this complication to date has not been reported after
      laparoscopic gastric bypass. We present and discuss a case of a patient who
      developed vague abdominal complaints 3 weeks after laparoscopic gastric bypass,
      and was diagnosed with portal venous thrombosis by computed tomography.

PMID- 15978166
TI  - Peripheral polyneuropathy from thiamine deficiency following laparoscopic Roux-en
      Y gastric bypass.
AB  - The neurologic form of beriberi has been described in multiple case reports
      following bariatric surgery for morbid obesity. Thiamine deficiency occurs due to
      marked emesis and/or altered absorption secondary to the reconfiguration of the
      gastrointestinal tract to achieve the malabsorption needed to achieve weight
      loss. This case report illustrates the typical presentation of a patient after
      gastric bypass, and highlights the symptoms that bariatric surgeons must detect
      and reviews the treatment.

PMID- 15978167
TI  - Symptomatic pneumoperitoneum after endoscopic removal of adjustable gastric band.
AB  - Endoscopic removal of an adjustable gastric band is a feasible procedure with few
      complications, according to our series of 8 patients. We report the case of a 56
      year-old woman who underwent endoscopic removal of a gastric band which had
      eroded through the gastric wall; this procedure was performed under general
      anesthesia, while the surgical group removed the subcutaneous port. The patient
      developed a large pneumoperitoneum after the procedure, and complained of back,
      shoulder and epigastric pain. A plain abdominal X-ray confirmed the
      pneumoperitoneum, and esophagogastric radiography with water-soluble contrast did
      not show a perforation. The treatment approach was conservative. This experience
      demonstrates an expected complication of endoscopic removal of an adjustable
      gastric band, and that the treatment may be conservative. The technique of band
      removal and the mechanism of pneumoperitoneum are discussed.

PMID- 15978168
TI  - Enterocutaneous fistula: a rare complication of laparoscopic adjustable gastric
      banding.
AB  - Morbid obesity is a refractory disease with serious co-morbidities. Laparoscopic
      adjustable gastric banding (LAGB) has generally been a safe and effective method
      for achieving sustained weight loss. We report a man who presented after LAGB
      with persistent wound infection at the access port-site, which failed
      conservative management. Diagnostic laparoscopy found an enterocutaneous fistula
      from herniated bowel (in a Richter's hernia) into which the catheter had eroded.
      The small bowel and fascial defect were repaired. The catheter was then clipped
      and divided, and the port was removed.

PMID- 15978169
TI  - Results of biliopancreatic diversion in two patients with Prader-Willi syndrome.
AB  - Prader-Willi Syndrome (PWS) is a genetic disorder characterized by hypotonia,
      mental retardation or learning disability, hyperphagia and compulsive eating due
      to hypothalamic dysfunction. Obesity is a major cause of increased morbidity and
      mortality among patients with PWS. Gastric restrictive surgery has been
      associated with partial breakdown of the staple-line in PWS. We report two
      patients with PWS associated with morbid obesity and obstructive sleep apnea who
      underwent biliopancreatic diversion (BPD). A 27-year-old male with BMI 52 kg/m(2)
      and a 20 year-old female with BMI 64 kg/m(2) underwent BPD. No perioperative
      complications were observed. After BPD, the male's BMI was 36.7 kg/m(2) at 12
      months and the female's BMI was 48.4 kg/m(2) at 28 months, with excess weight
      loss 58% and 48%, respectively. They developed loose stools associated with
      eating. These patients have shown a considerable improvement in hypersomnia and
      respiratory difficulties. BPD proved to be an effective approach to weight loss
      in PWS, resulting in improvement of sleep apnea, behavior problems and quality of
      life.

PMID- 15978170
TI  - Mathematical model of the rupture mechanism of intracranial saccular aneurysms
      through daughter aneurysm formation and growth.
AB  - OBJECTIVES: Daughter aneurysms have been strongly associated with saccular
      aneurysm rupture. We constructed a mathematical model to help explain this
      association as a possible hemodynamic mechanism for intracranial saccular
      aneurysm rupture. METHODS: Our model is based on the assumption that when an
      aneurysm reaches a state of imminent rupture, the weakest area of the aneurysm
      wall responds passively to a surge of intra-aneurysmal pressure by forming a
      daughter aneurysm that will be the site of the eventual rupture. The daughter and
      parent aneurysms were assumed to be spherical. Using mathematical modeling, the
      growth of the daughter aneurysm was observed. To obtain the change in tensile
      stress in the daughter aneurysm wall under constant pressure and changing
      geometry, the Law of Laplace was applied to the parent and the daughter
      aneurysms. RESULTS: The model reveals that the stress factor, i.e. tensile stress
      in the daughter aneurysm wall relative to the wall strength (rupture point), is
      dependent on two geometric parameters: the orifice factor (mu), which represents
      the relative size of the daughter aneurysm orifice radius to the parent aneurysm
      radius; and the aspect ratio (lambda), which represents the height-to-orifice
      ratio of the daughter aneurysm. As the daughter aneurysm develops, the stress
      factor first decreases to protect against rupture. Minimal stress is attained at
      an aspect ratio (lambda) of 0.577 regardless of the orifice factor. This is a
      relatively stable state. Further growth of the daughter aneurysm results in an
      increase of stress above the minimum, eventually leading to rupture at a stress
      factor of 1. A smaller orifice factor mu allows this aneurysm to grow to a higher
      aspect ratio lambda before rupture. DISCUSSION: Daughter aneurysm formation is a
      likely path to aneurysm rupture. The formation of a daughter aneurysm temporarily
      decreases the tensile stress within a parent aneurysm in which rupture is
      imminent, indicating a temporary protective role of daughter aneurysm
      development. Aneurysms harboring daughter aneurysms are at a more advanced stage
      of development, hence at a greater risk for rupture. The severity of the rupture
      risk can be estimated on the basis of daughter aneurysm geometry; aspect ratio
      lambda > 0.577 indicates a greater risk of rupture. Furthermore, daughter
      aneurysms with larger orifices are associated with a greater risk of rupture.

PMID- 15978171
TI  - Calpain inhibitor A-558693 in experimental focal cerebral ischemia in rats.
AB  - OBJECTIVES: Calpains are intracellular proteases, which are activated in various
      cerebral injuries. We studied the expression of mu-calpain in a model of focal
      cerebral ischemia/reperfusion and the efficacy of the calpain inhibitor A-558693.
      METHODS: A transient occlusion of the middle cerebral artery was produced in male
      Wistar rats by using the suture model with 3 hours of ischemia and 24 hours of
      reperfusion. Six animals were given the calpain inhibitor and six animals were
      treated with placebo. The infarct size was determined by the loss of the calpain
      substrate microtubule-associated protein-2 (MAP-2) immunohistochemistry using
      volumetry in serial slices of the brains. Furthermore mu-calpain positive-stained
      cells were detected by immunohistochemistry and western blotting. RESULTS: In
      placebo-treated animals the mu-calpain expression was significantly increased in
      the ischemic hemisphere compared with the contralateral non-ischemic hemisphere
      (88.6 versus 10.5% in the basal ganglia, 60.7 versus 10.7% in the cortex, p <
      0.001, respectively) with a subsequent loss its substrate MAP-2. However, the use
      of the calpain inhibitor A-558693 did not significantly change the mu-calpain
      expression, nor significantly reduce the infarct volume. DISCUSSION: The present
      data indicate that mu-calpain proteolysis plays an important role in the chain of
      events following cerebral ischemia. However, the calpain inhibitor A-558693
      failed to prevent these changes.

PMID- 15978172
TI  - Comparison of a 1-MHz and a 2-MHz probe for microembolus detection using
      transcranial Doppler ultrasound.
AB  - OBJECTIVES: Clinically silent microembolic signals (MES) can be detected by
      transcranial Doppler sonography (TCD). There is theoretical evidence that lower
      ultrasound emission frequencies may lead to a higher signal intensity and thus
      sensitivity to detect MES. We compared a 1-MHz probe with a 2-MHz probe regarding
      sensitivity in the detection of MES. Moreover, embolus detection by transcranial
      Doppler ultrasound is very time consuming and semi-automated detection is
      mandatory. Therefore, we studied an on-line algorithm using the bi-gate technique
      and the two transmission frequencies. METHODS: After defining detection
      thresholds of > or = 12 dB (1 MHz) and > or = 10 dB (2 MHz) with eight normal
      subjects as MES-negative controls, taking into account natural fluctuations of
      the Doppler spectrum, we studied 36 patients with ischaemic events and five
      asymptomatic patients with incidental embolic sources. All patients subsequently
      underwent a 1-hour unilateral embolus detection from the middle cerebral artery
      (MCA) or the posterior cerebral artery (PCA), respectively, using 1 and 2 MHz for
      30 minutes each in a randomized order. The software algorithm was compared with a
      blinded off-line analysis by an experienced observer as a gold standard. RESULTS:
      The investigator detected 198 MES (range 0-41 MES) in the recordings of 29
      patients out of the 41 patients using the 1-MHz probe and 101 MES (range 0-32
      MES) in the recordings of 14 patients using the 2-MHz probe (p = 0.0007).
      Sensitivity of the software to detect MES confirmed by the investigator was 31%
      using 1 MHz and 41% using 2 MHz. The positive predictive value was 6 and 30%,
      respectively. DISCUSSION: The sensitivity and positive predictive values of the
      automated algorithm to detect MES were unacceptably low for clinical practice
      with both frequencies. The use of 1 MHz instead of 2 MHz may, however, be useful
      when evaluating the recordings off-line by an experienced blinded observer.

PMID- 15978173
TI  - Lack of antiapoptotic effects of antiplatelet drug, aspirin and clopidogrel, and
      antioxidant, MCI-186, against focal ischemic brain damage in rats.
AB  - OBJECTIVES: This study evaluated the antiapoptotic effect of antiplatelet drugs,
      aspirin and clopidogrel, and the antioxidant drug, MCI-186, against focal
      cerebral ischemic rat brain damage. METHODS: Cerebral ischemia was mechanically
      induced by 2-hour occlusion of the left middle cerebral artery (MCA) using an
      intraluminal filament followed by 24-hour reperfusion. RESULTS: The cerebral
      infarct size was little affected by oral administration of 300 mg/kg aspirin, 30
      mg/kg clopidogrel or 100 mg/kg MCI-186, but was significantly reduced by 30 mg/kg
      cilostazol. However, intravenous administration of 10 mg/kg MCI-186 suppressed
      the infarct size. DNA fragmentation observed in the cortical tissues
      corresponding to the penumbral zone was not suppressed by aspirin, clopidogrel or
      MCI-186, but was significantly suppressed by cilostazol. Increased
      phosphorylation of phosphatase and tensin homolog deleted from chromosome 10
      (PTEN) and Bax protein, and decreased Akt/cyclic AMP response element binding
      protein (CREB) phosphorylation, including Bcl-2 protein in the vehicle-treated
      group were not affected by treatment with aspirin, clopidogrel and MCI-186,
      whereas those effects were reversed by cilostazol. CONCLUSION: Thus, it is
      suggested that antiplatelet drugs, aspirin and clopidogrel, and antioxidant drug,
      MCI-186, showed little antiapoptotic effect in contrast to cilostazol.

PMID- 15978174
TI  - Minor inflammation after surgical evacuation compared with fibrinolytic therapy
      of experimental intracerebral hemorrhages.
AB  - OBJECTIVES: Toxic components released from the intracerebral blood clot, such as
      thrombin and hemoglobin, potentially trigger brain edema formation and therefore
      favor an early evacuation of the clot. Despite a significant reduction in
      hematoma size in our porcine model of hematoma induction by injecting autologous
      blood ICP-controlled into the right frontal white matter with subsequent
      fibrinolysis using recombinant tissue-plasminogen activator (rt-PA) and
      aspiration of the liquefied clot (n = 9), local rt-PA promoted delayed
      perihematomatous edema formation and invoked a substantial inflammatory reaction
      compared with controls (n = 11). METHODS: We therefore modified our formerly
      developed porcine model of intracerebral hemorrhage in removing the hematoma by
      open craniotomy and suction of the clot in seven animals. The residual hematoma
      size and extent of perifocal edema were evaluated over 10 days on planimetry of
      the MRI data, and correlated to the histopathological changes of edema and
      inflammation found at autopsy. RESULTS: The edema volume on day 4 was
      significantly less in the surgical group compared with the lysis group (p <
      0.03). On day 10, however, the difference in edema size was not statistically
      significant compared with the lysis group (p < 0.07) and the control group (p <
      0.09). The inflammatory response was minor compared with the lysis and control
      group. DISCUSSION: In conclusion, despite a significant reduction in hematoma
      size by surgical removal of the clot, only the inflammatory response, but not the
      extent of delayed edema can be positively influenced.

PMID- 15978175
TI  - Attenuation of extravasation of tissue plasminogen activator by the free radical
      scavenger, edaravone: evaluation in a rat thromboembolic stroke model.
AB  - OBJECTIVES AND METHODS: Deleterious effects of tissue plasminogen activator (tPA)
      have been described recently in experimental studies. For example, tPA can
      aggravate ischemic neuronal damage through its proteolytic activity. The present
      study was undertaken to examine whether or not the free radical scavenger,
      edaravone, could prevent the extravasation of tPA administered for the purpose of
      fibrinolysis in a rat model of thromboembolic stroke. RESULTS: Significant
      amounts of tPA were extravasated through the cerebral vessels even when early
      recanalization was induced by administering tPA at 30 minutes after the onset of
      schema. Edaravone significantly attenuated such extravasation of tPA. CONCLUSION:
      In acute ischemic stroke patients, combination therapy using tPA with edaravone
      appears to be a reasonable strategy for diminishing the negative effects of tPA.

PMID- 15978176
TI  - Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral
      ischemia model.
AB  - BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that
      regulates the adaptive response to hypoxia in mammalian cells. It consists of a
      regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a
      constitutively expressed subunit, HIF-1beta. In this study, we investigated HIF
      1alpha naked DNA-induced angiogenesis in a cerebral ischemic model in vivo.
      METHODS: We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated
      HIF-1alpha DNA into the brain surface or the temporal muscle. We analysed whether
      HIF-1alpha induced angiogenic factors and collateral circulation. RESULTS: A
      histological section treated with HIF-1alpha DNA showed an increased expression
      of HIF1 a and VEGF with collateral circulation, in comparison with control DNA (p
      < 0.01). The HIF-1alpha transcription factor is able to promote significant
      angiogenesis development. CONCLUSION: These results suggest the feasibility of a
      novel approach for therapeutic collateral circulation of cerebral ischemia in
      which neovascularization may be achieved indirectly using a transcriptional
      regulatory strategy.

PMID- 15978177
TI  - Early administration of a second-generation perfluorochemical decreases ischemic
      brain damage in a model of permanent middle cerebral artery occlusion in the rat.
AB  - OBJECTIVES: Perfluorochemicals (PFCs) may exert a neuroprotective function in the
      early phase of ischemia by improving the oxygen supply to the endangered tissue.
      We have, therefore, investigated the effect of Oxycyte, a second-generation
      perfluorocarbon solution, on the extent of early ischemic brain damage in a model
      of permanent focal cerebral ischemia. METHODS: Eight hours of permanent focal
      cerebral ischemia was induced in isoflurane anesthetized male Sprague-Dawley rats
      by unilateral middle cerebral artery (MCA) thread occlusion under the control of
      laser Doppler flowmetry (LDF). Animals were assigned to one of the following
      treatment groups: nO2-NaCl and hO2-NaCl-NaCl (0.9%, 1 ml/100 g i.v.) and nO2
      Oxycyte and hO2-Oxycyte-Oxycyte (1 ml/100 g i.v.). The injection of NaCl or
      Oxycyte was performed immediately after MCA occlusion. After injection, breathing
      was changed to pure oxygen in groups hO2-NaCl and hO2-Oxycyte while animals in
      groups nO2-NaCl and nO2-Oxycyte were allowed to breathe air. The necrotic volume
      was calculated from serial coronal sections stained with silver-nitrate. In
      addition, nitrotyrosine production was studied by immunohistochemistry. RESULTS:
      Upon MCA occlusion, animals showed a reduction of cerebral blood flow of
      approximately 80% of the LDF signal in all groups. Hemodynamic and metabolic
      parameters were not affected by the infusion of Oxycyte. The total infarct volume
      was reduced in hO2-Oxycyte animals [group nO2-NaCl: 341+/-31 mm3 (mean+/-SD),
      group hO2-NaCl: 351+/-33 mm3, group nO2-Oxycyte: 354+/-24 mm3, and group hO2
      Oxycyte: 300+/-29 mm3, p < 0.05 versus all other groups]. Moreover, hO2-Oxycyte
      animals showed lesser intensity of nitrotyrosine staining when compared with hO2
      NaCl animals. DISCUSSION: These results suggest that Oxycyte administered
      immediately after the onset of vascular occlusion may exert neuroprotective
      effects in the early phase of brain ischemia.

PMID- 15978178
TI  - Baseline 11C-methionine PET reflects the natural course of grade 2
      oligodendrogliomas.
AB  - OBJECTIVES: The aim of the present study was to assess the usefulness of positron
      emission tomography (PET) with the amino acid tracer 11C-methionine (MET) as a
      predictor of time to progression (TTP) in patients with supratentorial grade 2
      gliomas. METHODS: Twenty-seven patients with glioma grade 2 subjected to a
      baseline PET scan received no anti-tumour treatment except for a diagnostic
      operation, and were followed until tumour progression. The prognostic impact of
      the MET uptake and of other prognostic factors was studied. RESULTS: Twenty-five
      of the patients (93%) experienced tumour progression after a median of 103 weeks.
      Low uptake of MET was a predictor for long TTP in patients with
      oligodendrogliomas (p = 0.04) but not in astrocytomas/oligoastrocytomas. Other
      predictors for long TTP were oligodendroglioma histology (p = 0.009) and seizures
      as presenting symptom (p = 0.03). Favourable prognostic factors for overall
      survival were oligodendroglioma histology (p = 0.002) and good performance status
      (p = 0.03). CONCLUSIONS: PET MET has a definite role in the therapeutic
      management of grade 2 gliomas. However, for the optimal use of PET MET in the
      clinical management of these patients, histological subclassification of the
      tumour is required.

PMID- 15978179
TI  - Boston Carpal Tunnel Questionnaire: the influence of diagnosis on patient
      oriented results.
AB  - OBJECTIVES: To evaluate the influence of the patient-physician interaction and
      the instrumental awareness of the assessment of patients' answers to a carpal
      tunnel syndrome-specific questionnaire. METHODS: We performed a prospective study
      of the results of a self-administered questionnaire for carpal tunnel syndrome
      before and after electrodiagnosis. Thirty-two consecutive patients were referred
      to our neurophysiological laboratory for suspected carpal tunnel syndrome. A
      patient-oriented evaluation using the Italian version of the Boston Carpal Tunnel
      Questionnaire (BCTQ), a widely used disease-specific questionnaire, was carried
      out before the clinical interaction was performed. The assessment was performed
      by means of a neurophysiological classification. After the communication of the
      result, the BCTQ was again administered. RESULTS: The comparison of the BCTQ
      results, obtained PRE and POST clinical interaction, showed a significant
      reduction in the reported symptoms and hand function impairment not related to
      the neurophysiological results. CONCLUSIONS: The findings of the patient-oriented
      evaluation are significantly influenced by the communication of the assessment
      results. In prospective studies, the baseline assessment by means of a patient
      oriented evaluation should consistently be performed in all patients at the same
      stage of the clinical process.

PMID- 15978180
TI  - Beta-amyloid-induced reactive astrocytes display altered ability to support
      dendrite and axon growth from mouse cerebral cortical neurons in vitro.
AB  - OBJECTIVES: The presence of beta-amyloid (betaA) deposition, induction of
      reactive gliosis and dystrophic neurites, is a characteristic feature of neuritic
      plaques in Alzheimer's disease. In vitro, betaA-exposed astrocytes become
      reactive, similar to astrocytes in contact with betaA plaques in vivo. How betaA
      exposed reactive astrocytes support neuron process growth, however, is not well
      defined. Therefore, we used neuron/astrocyte co-cultures in which astrocytes had
      been grown on betaA, to assess whether process growth was altered. METHODS:
      Purified rat cortical astrocytes were plated on the betaA peptide's neurotoxic
      fragment (25-35), the scrambled (35-25) peptide, or poly-D-lysine alone and grown
      to confluency before mouse cortical neurons were seeded at low density onto the
      astrocyte monolayer. Cell survival was assessed using trypan blue, lactate
      dehydrogenase release and propidium iodide. Process growth was analyzed using
      specific antibodies against MAP2 and the 200 kDa neurofilament subunit (NF-H) to
      identify dendrites and axons, respectively. RESULTS: betaA-exposed astrocytes
      changed dramatically from their flat polygonal shape into stellate process
      bearing morphology. Viability however, was not affected. Immunocytochemical
      analysis of neuronal processes using anti-MAP2 and anti-NF-H, demonstrated that
      betaA (25-35)induced reactive astrocytes had an altered ability to support
      dendrite and axon growth after 3 days in vitro. Indeed, primary dendrite number
      and axon length were decreased by 30 and 26%, respectively, compared with control
      astrocytes, whereas individual primary dendrite length increased by 20%.
      Astrocyte support of dendritic branching, however, was not affected by betaA.
      DISCUSSION: We conclude that an astrocyte reaction to betaA may contribute, in
      part, to neuronal dystrophy associated with betaA plaques.

PMID- 15978181
TI  - Pramipexole has ameliorating effects on levodopa-induced abnormal dopamine
      turnover in parkinsonian striatum and quenching effects on dopamine-semiquinone
      generated in vitro.
AB  - OBJECTIVES AND METHODS: To clarify the effects of a non-ergot dopamine agonist
      pramipexole on levodopa-induced abnormal dopamine metabolism in the parkinsonian
      model, we examined striatal changes in dopamine and its metabolites after
      repeated administration of pramipexole and/or levodopa using 6-hydroxydopamine
      lesioned hemi-parkinsonian mice. Moreover, the effects of pramipexole on dopamine
      semiquinones were also accessed using an in vitro dopamine-semiquinone generating
      system to elucidate its neuroprotective property against dopamine quinone-induced
      neurotoxicity that appears as dopamine neuron-specific oxidative stress. RESULTS:
      Combined administration of pramipexole (0.5 or 1 mg/kg/day, 7 days) selectively
      suppressed the levodopa-induced (50 mg/kg/day) increase of striatal dopamine
      turnover in the parkinsonian side, but not in the non-lesioned side. In addition
      to the antioxidant properties previously reported, it was clarified that
      pramipexole scavenged dopamine-semiquinones generated in a dose-dependent manner
      either in simultaneous incubation or post-incubation. DISCUSSION: The
      neurotoxicity of dopamine quinones that appear as dopaminergic neuron-specific
      oxidative stress has recently been known to play a role in the pathogenesis of
      Parkinson's disease and neurotoxin-induced parkinsonism. Therefore, the present
      results revealed that pramipexole possesses neuroprotective effects against
      abnormal dopamine metabolism in excessively levodopa-administered parkinsonian
      brains and against cytotoxic dopamine quinones generated from excess dopamine,
      preventing consequently dopaminergic neuronal damage induced by excess dopamine
      or levodopa.

PMID- 15978182
TI  - The syndrome of hydrocephalus in young and middle-aged adults (SHYMA).
AB  - OBJECTIVES: Currently, headache, nausea/vomiting, visual changes, and altered
      mental status are accepted as indications for the evaluation of hydrocephalus in
      children; while dementia, gait apraxia, and urinary incontinence remain
      indications in the elderly. The clinical presentation of hydrocephalus in young
      and middle-aged adults remains poorly described. Hence, middle-aged patients with
      mild gait, cognitive, or urinary symptoms unaccompanied by clear exam findings
      often remain undiagnosed and untreated. METHODS: We report the clinical
      presentation, treatment, and outcomes of 46 adults (ages 16-55 years) presenting
      with congenital, acquired, or idiopathic hydrocephalus with imaging-documented
      ventriculomegaly and elevated CSF pressure. RESULTS: Primary symptoms were
      related to gait (70%), cognition (70%), urinary urgency (48%), and headaches
      (56%). Eighty-four percent complained of impaired job performance. The exam
      findings were subtle or absent (no gait apraxia, minor gait changes in 42.9%,
      mildly abnormal Mini Mental State exams in only 14.3%, and incontinence in only
      3.6%). Twenty-nine patients underwent ventriculoperitoneal (VP) shunting, and 11
      endoscopic third ventriculostomy, of whom six subsequently required a VP shunt.
      Symptomatic improvement was observed in 93% of patients 16+/- 11 months after
      shunting (56% complete resolution, 37% partial resolution). Patients had been
      followed for their symptoms an average of 6 years (range, 1-30) prior to
      diagnosis. DISCUSSION: We propose that there exists a clinically distinct
      syndrome of hydrocephalus in young and middle-aged adults (SHYMA) that comprises
      hydrocephalus of all etiologies. SHYMA is characterized by complaints of impaired
      gait, cognition, bladder control, and headaches, with a discrepancy between the
      prominence of symptoms and the subtlety of clinical signs. Despite the subtlety
      of clinical signs, CSF diversion treatment is effective at resolving
      symptomatology.

PMID- 15978183
TI  - Age-dependent differences in androgen binding affinity in a family with spinal
      and bulbar muscular atrophy.
AB  - OBJECTIVES: To investigate androgen receptor (AR) function in spinal and bulbar
      muscular atrophy (SBMA). METHODS: A kindred was identified with five individuals
      carrying the AR gene CAG repeat expansion that causes SBMA. Androgen binding was
      measured in cultured genital skin fibroblasts from three affected individuals.
      One newborn, pre-symptomatic, individual showed normal androgen binding, but two
      older, symptomatic individuals showed a decrease in androgen binding affinity.
      This difference was not related to AR CAG repeat size, as all affected
      individuals in this kindred had 49 repeats (normal range 6-35). Post-mortem
      analysis in one subject confirmed the signs of androgen insufficiency in the
      testis, with marked seminiferous tubule atrophy, and the absence of germinal
      cells. The characteristic neuronal depletion in the anterior horn gray matter was
      also observed. CONCLUSION: This report raises the possibility that age- or
      puberty-related changes in androgen binding could occur, which could potentially
      contribute to the progressive development of androgen resistance in affected men.

PMID- 15978184
TI  - D-galactose injured neurogenesis in the hippocampus of adult mice.
AB  - OBJECTIVES: We studied the effects of the reactive oxygen species (ROS) on neural
      progenitor cell proliferation and survival in the dentate gyrus (DG). METHODS:
      The adult mice were treated with D-galactose for 7 weeks to mimic natural aging
      in mice. The level of malondialdehyde (MDA) and the activities of antioxidant
      enzymes in the serum were detected. Neurodegeneration and neurogenesis in the
      hippocampus were explored using terminal deoxynucleotidyltransferase-mediated UTP
      nick-end labeling (TUNEL) to detect the dying cells and bromodeoxyuridine (BrdU)
      was used to label the newly born cells. RESULTS: After the treatment of D
      galactose, the level of MDA increased and the activities of the antioxidant
      enzyme decreased in the serum. TUNEL-positive cells significantly increased in
      the DG, CA1 and CA3 subfields. The BrdU-labeled proliferating cells and surviving
      cells in the DG decreased significantly in number after D-galactose treatment.
      DISCUSSION: D-Galactose induced the impairment of neurogenesis in the DG, which
      is similar to natural aging in mice. ROS accumulation as a result of D-galactose
      may be related to the decrease of neurogenesis in the DG.

PMID- 15978185
TI  - Inhibition of AF116909 gene expression enhances the differentiation of neural
      stem cells.
AB  - OBJECTIVES: Neural stem cells (NSCs) are self-renewed, pluripotent cells that can
      differentiate into neurons, astrocytes and oligodendrocytes. Such multipotency
      that allows production of specific types of nerve cells for basic research and
      therapeutic purposes depends on how these cells are directed in their
      differentiation. Here, we investigate the function of the AF116909 gene in the
      differentiation of NSC. METHODS: NSC culture was isolated from the striatum
      corpora of embryonic brain tissues in a 14-day pregnant rat. A constructed RNAi
      (RNA-mediated interference) vector was transfected to knock down the expression
      of this gene. Afterwards, RT-PCT was applied to examine the presence of
      endogenous AF116909 mRNA and the effect of RNA interference. RESULTS: After the
      knockdown of this gene, we detected that the differentiation rate of cells was
      enhanced to 80% on the 11th day in comparison with 12% in the control cells
      transfected with the expression vector alone. DISCUSSION: These findings suggest
      that AF116909 functions in inhibiting the differentiation of NSCs, and AF116909
      gene-targeting by RNAi provides a useful method to study the differentiation
      mechanisms of NSCs.

PMID- 15978186
TI  - Cerebrospinal fluid superoxide dismutase and serum malondialdehyde levels in
      patients with aneurysmal subarachnoid hemorrhage: preliminary results.
AB  - OBJECTIVES: Experimental studies provide evidence that oxidative damage plays a
      role in the development of vasospasm after aneurysmal subarachnoid hemorrhage
      (SAH) but data from human studies is still limited. The purpose of this study was
      to investigate the time course of cerebrospinal fluid (CSF) superoxide dismutase
      (SOD) and serum malondialdehyde (MDA) changes in patients with aneurysmal SAH.
      METHODS: SOD in CSF and MDA in the serum were detected on days 1-3, 5 and 7 after
      aneurysmal SAH in 21 patients, and the results were compared with 15 patients
      with hydrocephalus. The results were also compared with those of clinical
      parameters including the patient's outcome at 6 months. RESULTS: The mean CSF SOD
      levels were lower and serum MDA levels were higher than the controls. Patients
      with a high amount of blood within the cisterns had a trend to decreased SOD
      while increasing MDA levels. CONCLUSION: These preliminary results suggest that
      the levels of antioxidants are decreased after the onset of SAH in the early
      period, possibly because of increased oxidative stress. Reactive oxygen-mediated
      oxidative damage may play an important role in inflammation after SAH.

PMID- 15978187
TI  - Cardiovascular risk in Chinese patients with chronic kidney diseases: where do we
      stand?

PMID- 15978188
TI  - Prevalence and risk factors of urinary incontinence in Fuzhou Chinese women.
AB  - BACKGROUND: We randomly sampled a healthy community to evaluate the prevalence
      and associated risk factors of urinary incontinence. METHODS: The survey was
      performed in Fuzhou, China. Of women over twenty years of age in the city, 3.0%
      were randomly selected and 4684 evaluated by Bristol Female Urinary Tract
      Symptoms Questionnaire. RESULTS: Of the women in Fuzhou, 19.0% had urinary
      incontinence. The prevalence of stress incontinence, urge incontinence and mixed
      incontinence was 16.6% (n = 777), 10.0% (n = 468), 7.7% (n = 360) respectively.
      The prevalence of the three types of urinary incontinence increased significantly
      with age (P < 0.01). In multiple logistic models, age (OR, 1.3, 95% CI, 1.1-1.4),
      vaginal delivery (3.0, 1.9-4.7), parity > 2 (2.1, 1.5-2.9), hypertension (2.7,
      1.4-5.6), constipation (2.6, 1.8-3.8), alcohol consumption (4.7, 1.1-20.2),
      episiotomy (1.7, 1.4-2.0), higher body mass index (BMI, 1.8, 1.5-2.2) and
      unskilled worker (0.7, 0.5-0.8) were potential risk factors for stress
      incontinence. Urge incontinence was associated with age (OR, 1.3, 95% CI, 0.9
      1.3), menopause (1.6, 1.1-2.4), Caesarean delivery (0.2, 0.1-0.5), parity > 2
      (2.6, 1.8-3.8), constipation (2.3, 1.4-3.7), foetal birthweight (1.7, 1.1-2.4),
      episiotomy (1.4, 1.1-1.8), higher BMI (1.5, 1.2-2.0) and unskilled worker (0.7,
      0.5-0.9). CONCLUSIONS: The prevalence of urinary incontinence and its subtypes in
      Chinese women is lower than that of occidental women. In China, age, vaginal
      delivery, parity, hypertension, constipation, alcohol consumption, episiotomy,
      higher BMI are potential risk factors for stress incontinence. Urge incontinence
      is associated with age, menopause, Caesarean delivery, parity, constipation,
      foetal birthweight, episiotomy, higher body mass index.

PMID- 15978189
TI  - Reversal of MDR1 gene-dependent multidrug resistance using short hairpin RNA
      expression vectors.
AB  - BACKGROUND: RNA interference using short hairpin RNA (shRNA) can mediate sequence
      specific inhibition of gene expression in mammalian cells. A vector-based
      approach for synthesizing shRNA has been developed recently. Overexpression of P
      glycoprotein (P-gp), the MDR1 gene product, confers multidrug resistance (MDR) to
      cancer cells. In this study, we reversed MDR using shRNA expression vectors in a
      multidrug-resistant human breast cancer cell line (MCF-7/AdrR). METHODS: The two
      shRNA expression vectors were constructed and introduced into MCF-7/AdrR cells.
      Expression of MDR1 mRNA was assessed by RT-PCR, and P-gp expression was
      determined by Western Blot and immunocytochemistry. Apoptosis and sensitization
      of the breast cancer cells to doxorubicin were quantified by flow cytometry and
      methyl thiazolyl tetrazolium (MTT) assays, respectively. Cellular daunorubicin
      accumulation was assayed by laser confocal scanning microscopy (LCSM).
      Statistical significance of differences in mean values was evaluated by Student's
      t tests. P < 0.05 was considered statistically significant. RESULTS: In MCF
      7/AdrA cells transfected with MDR1-A and MDR1-B shRNA expression vectors, RT-PCR
      showed that MDR1 mRNA expression was reduced by 40.9% (P < 0.05), 30.1% (P <
      0.01) (transient transfection) and 37.6% (P < 0.05), 28.0% (P < 0.01) (stable
      transfection), respectively. Western Blot and immunocytochemistry showed that P
      gp expression was significantly and specifically inhibited. Resistance against
      doxorubicin was decreased from 162-fold to 109-fold (P < 0.05), 54-fold (P <
      0.01) (transient transfection) and to 108-fold (P < 0.05), 50-fold (P < 0.01)
      (stable transfection). Furthermore, shRNA vectors significantly enhanced the
      cellular daunorubicin accumulation. The combination of shRNA vectors and
      doxorubicin significantly induced apoptosis in MCF-7/AdrR cells. CONCLUSIONS:
      shRNA expression vectors effectively reduce MDR expression in a sustained fashion
      and can restore the sensitivity of drug-resistant cancer cells to conventional
      chemotherapeutic agents.

PMID- 15978190
TI  - Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress
      models in mice.
AB  - BACKGROUND: Up to now there have been no satisfactory drugs to treat psychiatric
      disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new
      type of bioactive compound from entomopathogenic fungi. Our previous
      investigations have shown that BCEF has an inhibition effect on monoamine
      oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing
      the antidepressant effects and its mechanism of BCEF in the chronic unpredictable
      stress models in mice. METHODS: The antidepressant effects of BCEF were examined
      on the chronic unpredictable stress models in mice. Sixty mice were randomly
      divided to six groups. Animals were housed and isolated except saline group. Mice
      were exposed to different stressors per day randomly from day 1 to day 21. Body
      weight were weighed on day 1, day 10 and on day 21 during the 21-day stress
      procedure. Awarding response was detected by using method of calculating the 24
      hour consumption of saccharum water. Step through test was used to evaluate the
      behavioral response. AVP contents in plasma were also detected by using
      radioimmunoassays. RESULTS: Chronic unpredictable stress resulted in a
      significant decrease of the body weight and could apparently cause escape
      behavior disturbance and gradual reduction of sensitivity to reward in animal
      models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate
      the decreased body weight and effectively reverse the escape behavior
      disturbance. The gradual reduction of sensitivity to reward, the anhedonic state,
      was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also
      effectively restore the AVP content in the plasma. CONCLUSIONS: This evidence
      suggests that BCEF can effectively inhibit the depression behavior and show
      strong antidepressant effect. BCEF can effectively restore the plasma AVP release
      and this may be an important mechanism of its antidepressant effect.

PMID- 15978191
TI  - RANTES gene single nucleotide polymorphisms and expression in patients with
      chronic hepatitis B virus infection.
AB  - BACKGROUND: Regulated on activation, normal T-cell expressed and secreted
      (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The
      process is involved in both acute and chronic phases of inflammation. The present
      study was to ascertain the possible correlations between chronic hepatitis B
      virus (HBV) infection and the RANTES gene polymorphisms and their expression.
      METHODS: The study included 130 HBV negative healthy donors and 152 patients with
      chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR)
      and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES
      gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet
      depleted plasma were detected by enzyme linked immunosorbent assay (ELISA).
      RESULTS: RANTES alleles -403G, -28C and In1.1T were the predominant alleles in
      the subjects studied. No significant correlation was found between CHB infection
      and the RANTES alleles, while a significant correlation was found between CHB
      infection and increased RANTES expression in platelet depleted plasma (P < 0.05).
      CONCLUSIONS: SNPs in RANTES gene do not affect chronic HBV infection or the
      outcome of interferon-alpha treatment in patients positive for HBV "e" antigen
      (HBeAg+). However, patients with CHB infection express the higher levels of
      plasma RANTES, which is thus associated with CHB infection.

PMID- 15978192
TI  - Association between coinfection of Porphyromonas gingivalis, Actinobacillus
      actinomycetemcomitans and Treponema denticola and periodontal tissue destruction
      in chronic periodontitis.
AB  - BACKGROUND: The association between the infection of Porphyromonas gingivalis,
      Actinobacillus actinomycetemcomitans and Treponema denticola in chronic
      periodontitis (CP) and the severity of periodontal disease remains to be
      elucidated. The aim of this study was to investigate the subgingival infection
      frequencies of three periodontopathic bacteria in Chinese CP patients and to
      evaluate the correlations between infection by these bacteria and periodontal
      destruction. METHODS: A multiple PCR assay using primers derived from 16SrDNA
      genes of P. gingivalis, A. actinomycetemcomitans and T. denticola was established
      to measure simultaneously the presence of the three microbes in 162 subgingival
      samples from 81 Chinese CP patients. RESULTS: The positive rates of P.
      gingivalis, A. actinomycetemcomitans and T. denticola in the subgingival samples
      were 84.6%, 83.3% and 88.3%, respectively. Of the subgingival samples, 68%
      revealed the coinfection of all the three microbes. The infection rates with P.
      gingivalis, A. actinomycetemcomitans or T. denticola alone was 5.9% (1/17), 17.6%
      (3/17) and 76.5% (13/17), respectively. A close association was present between
      the A. actinomycetemcomitans infection and gingival index (GI) (P < 0.01), but
      not between P. gingivalis or T. denticola infection and GI (P > 0.05). P.
      gingivalis and A. actinomycetemcomitans were more frequently detectable in middle
      and deep pockets than in shallow ones (P < 0.01), while T. denticola was found
      remarkably often in deep pockets (P < 0.05). The coinfection rate of the three
      microbes was significantly higher in sites with severe periodontitis than in
      those with mild periodontitis (P < 0.01). CONCLUSIONS: The multiple PCR
      established in this study can be used as a sensitive and specific method to
      simultaneously detect all three microbes in subgingival samples. A.
      actinomycetemcomitans infection may be associated with CP and play an important
      role in the periodontal tissue destruction. The coinfection of P. gingivalis, A.
      actinomycetemcomitans and T. denticola can cause more serious periodontal
      destruction than infection of any one or two of the three microbes.

PMID- 15978193
TI  - Clinical misdiagnosis of solid pseudopapillary tumour of pancreas.
AB  - BACKGROUND: Since being reclassified by WHO in 1996, solid pseudopapillary tumour
      (SPT) of pancreas has been recognized as the internationally accepted name.
      Clinicians are lacking in knowledge of this rare disease so the misdiagnosis and
      inappropriate therapy are hard to avoid. The clinic data on 22 patients were
      summarized to study the misdiagnosis and treatment of a sample of SPTs. METHODS:
      Twenty-two female patients with SPT were studied retrospectively and divided into
      two groups, the misdiagnosed group and the correctly diagnosed one. The analyses
      were performed with Fisher test with accurate probability for categorical data,
      and Kruskal-Wallis test for ranked data. RESULTS: The rate of misdiagnosis in
      this sample was 45.5%. The misdiagnosed SPTs were apt to be the incomplete
      capsule ones (P = 0.020), which resulted in obvious difficulties during operation
      (P = 0.024). In the misdiagnosed SPT group, the medical expenses increased
      significantly (P = 0.042), and the number of days in hospital greater than in
      correctly diagnosed group (P = 0.041). CONCLUSIONS: Although SPT has low
      malignancy with excellent prognosis after surgical treatment in most patients,
      the misdiagnosis of SPT increases the social and economic burdens on patients. It
      is important to analyse the causes of misdiagnosis.

PMID- 15978194
TI  - Transplantation of human limbal cells cultivated on amniotic membrane for
      reconstruction of rat corneal epithelium after alkaline burn.
AB  - BACKGROUND: The transplantation of limbal epithelial cells cultivated on amniotic
      membrane is a newly developed treatment for limbal stem cell deficiency. The
      purpose of our study was to investigate the biological characteristics of limbal
      epithelial cells and evaluate the effect of transplantation of cultivated human
      limbal epithelial cells on ocular surface reconstruction in limbal stem cell
      deficiency rat model. METHODS: Human limbal cells were isolated and cultivated in
      vitro. Cytokeratins 3, 12, and 19 (K3, K12 and K19) and p63 were detected by
      immunofluorescent staining or RT-PCR. BrdU labelling test was used to identify
      the slow cycling cells in the cultures. Limbal stem cell deficiency was
      established in rat cornea by alkali burn. Two weeks after injury, the rats
      received transplants of human limbal stem cells cultivated on amniotic membrane
      carrier. The therapeutic effect was evaluated by slit lamp observation, Hemotoxin
      and Eosin (HE) staining and immunofluorescent staining. RESULTS: On day 7 in
      primary culture, p63 and K19 were strongly expressed by most cells but only a few
      cells expressed K3. On days 14 and 21, p63 and K19 were still expressed by a
      majority of cells, but the expressive intensity of p63 decreased in a number of
      cells, while the proportion of K3 positive cells increased slightly and some
      cells coexpressed p63 and K3. RT-PCR showed that gene expression of both p63 and
      K12 were positive in cultivated limbal cells, but in mature superficial
      epithelial cells, only K12 was detected. BrdU labelling test showed that most
      cells were labelled with BrdU after 7 days' labelling and BrdU label retaining
      cells were observed after chasing for 21 days with BrdU free medium. For in vivo
      test, slit lamp observation, HE staining and immunofluorescent staining showed
      that the rats receiving transplant of human limbal stem cells cultivated on
      amniotic membrane grew reconstructed corneas with intact epithelium, improved
      transparency and slight or no neovascularization. A majority of epithelial cells
      of the reconstructed cornea were positive to antihuman nuclear antibody and cells
      expressing K3 were found mainly in superfacial epithelium. CONCLUSIONS: Limbal
      stem cells can be cultivated in vitro: the cells are characterized by high
      proliferation and slow cycling and identified as p63/K19 positive and K3/K12
      negative. During culture, some stem cells can proliferate and differentiate into
      mature cornea epithelial cells. Amniotic membrane is a suitable carrier for
      limbal stem cells. Transplantation of human limbal stem cells cultivated on
      amniotic membrane can functionally reconstruct rat cornea with limbal stem cell
      deficiency.

PMID- 15978195
TI  - Chitosan-DNA microparticles as mucosal delivery system: synthesis,
      characterization and release in vitro.
AB  - BACKGROUND: Mucosal immunity is important to defense against dental caries. To
      enhance mucosal immunity, a DNA vaccine mucosal delivery system was prepared by
      encapsulating anticaries DNA vaccine (plasmid pGJA-P/VAX) in chitosan under
      optimal conditions and the characteristics of the microparticles was
      investigated. Furthermore, the release properties and protective action of
      microparticles for plasmid were studied in vitro. METHODS: Plasmid loaded
      chitosan microparticles were prepared by complex coacervation. Three factors,
      concentration of DNA, sodium sulfate, and the chitosan/DNA ratios in complexes
      [better expressed as N/P ratio: the number of poly nitrogen (N) per DNA phosphate
      (P)] influencing preparation were optimized by orthogonal test. The
      characteristics of microparticles were evaluated by scanning electron microscopy
      (SEM) and confocal laser scanning microscopy (CLSM). DNA release rate of
      microparticles in similar gastro fluid (SGF) or similar intestinal fluid (SIF) at
      37 degrees C was determined by ultraviolet spectrophotometry. RESULTS: High
      encapsulation efficiency (96.8%) was obtained with chitosan microparticles made
      under optimal conditions of 50 mmol/L Na2SO4, 200 microg/ml DNA and N/P ratio of
      4. The size of particles was about 4 to 6 microm. The encapsulation process did
      not destroy the integrity of DNA. When incubated with SIL, after a release of
      about 10% in the first 60 minutes, no further DNA was released during the
      following 180 minutes. When incubated with SGL, the microparticles released a
      small burst (about 11%) in the first 60 minutes, and then slowly released at a
      constant, but different rate. CONCLUSIONS: These chitosan microparticles showed
      suitable characteristics in vitro for mucosal vaccination and are therefore a
      promising carrier system for DNA vaccine mucosal delivery.

PMID- 15978196
TI  - Mycobacterium bovis-Bacillus Calmette-Guerin and asthma.

PMID- 15978197
TI  - Protective effects of Ginkgo biloba extract 761 against glutamate-induced
      neurotoxicity in cultured retinal neuron.

PMID- 15978198
TI  - Sputum interleukin-17 is increased and associated with airway neutrophilia in
      patients with severe asthma.

PMID- 15978199
TI  - Experimental bladder defect in rabbit repaired with homologous bladder
      extracellular matrix graft.

PMID- 15978200
TI  - Intramural hematoma of the aorta: a case report.

PMID- 15978201
TI  - Trauma induced thyroid storm complicated by multiple organ failure.

PMID- 15978202
TI  - Five cases of cystic osteoechinococcosis.

PMID- 15978203
TI  - Mutations of connexin43 in fetuses with congenital heart malformations.
AB  - BACKGROUND: Gap junction channels formed by connexin43 (Cx43) protein are
      important in cardiac morphogenesis, and Cx43 gene is thought to be associated
      with congenital heart malformation (CHM). This study was undertaken to detect the
      mutations of Cx43 in fetuses with CHM. METHODS: Cx43 extron DNA was amplified by
      PCR from 16 fetuses with a variety of CHM. The PCR products were analyzed by SSCP
      and DNA sequencing. Thirty children who had no CHM were selected as controls.
      RESULTS: Eight homozygous mutations of Cx43 were observed in a fetus with double
      outlet right ventricule (DORV), five of the 8 mutations were missense mutations
      including Arg239Trp, Ser251Thr, Ala253Pro, Pro283Leu and Thr290Asn, and the
      remaining 3 were silent polymorphisms including Gly252Gly, Pro256Pro and
      Thr275Thr. No mutations were found in other fetuses and the control group.
      CONCLUSIONS: Mutations of Cx43 may be associated with congenital conotruncal
      anomalies. PCR-SSCP is an effective method for screening the mutations of Cx43.

PMID- 15978204
TI  - Expression of glucocorticoid receptor isoforms in cutaneous hemangiomas and
      vascular malformations.
AB  - BACKGROUND: Hemangiomas are the most common tumors in children. Some hemangiomas
      may require intervention because of their location, size, behavior, or potential
      for important complications. Pharmacological therapy with glucocorticoids is the
      mainstay treatment, but there is no consensus on therapeutic regimens or
      candidate selection, therapeutic efficacy varies, and the mechanism mediating the
      beneficial effects of glucocorticoids remains unclear. This study was performed
      to investigate the expression patterns of the glucocorticoid receptor (GR) and
      its alpha isoform (GRalpha) in cutaneous hemangiomas and vascular malformations.
      METHODS: SP immunohistochemical technique was used to examine the expression of
      GR(e-20) (GR) and GR(p-20) (GRalpha) on vascular endothelial cells in 80
      specimens that included 33 proliferating hemangiomas, 32 involuting hemangiomas,
      7 vascular malformations as well as 8 normal skin tissues, all obtained from
      infants and children. GR and GRalpha expression in prepared tissue slides were
      examined using automated computer-assisted microscopic analysis. Mean gray scale
      values were compared among the various tumor types. RESULTS: The mean gray scale
      values of GR were 127.0 +/- 6.4 and 121.4 +/- 6.6 in hemangiomas and vascular
      malformations respectively, but this difference was not statistically significant
      (P = 0.104). However, these values were all markedly higher than that of normal
      skin, which was only 108.6 +/- 6.8 (P = 0.001 and P = 0.000 for comparison with
      hemangiomas and vascular malformations respectively). The gray scale of GR in
      proliferation and involuting hemangiomas were 127.9 +/- 4.8 and 126.0 +/- 5.8
      respectively, but this difference was not significant (P = 0.146). However,
      GRalpha expression in hemangiomas, vascular malformations and normal skin
      declined gradually in stepwise fashion (127.3 +/- 5.4, 120.4 +/- 6.1 and 109.9 +/
      5.3 respectively; P < 0.001). GRalpha expression was higher in proliferating
      hemangiomas than in involuting hemangiomas (127.2 +/- 6.3 and 122.5 +/- 6.3; P =
      0.004). CONCLUSIONS: GR and GRalpha are strongly expressed in hemangiomas and
      vascular malformations. The expression of GRalpha is closely related to the phase
      of the hemangioma. Determination of GR and GRalpha may be a positive significance
      to understand the information of hemangiomas and vascular malformations and may
      further help determining proper strategies of steroid therapy for hemangiomas and
      vascular malformations.

PMID- 15978205
TI  - Effects of ribozyme targeting platelet-derived growth factor receptor beta
      subunit gene on the proliferation and apoptosis of hepatic stellate cells in
      vitro.
AB  - BACKGROUND: Activation and proliferation of hepatic stellate cells (HSC) is
      essentially involved in the development and progression of hepatic fibrosis. The
      most potent growth factor for HSC is platelet-derived growth factor receptor
      (PDGF) and PDGF receptor beta subunit (PDGFR-beta) is the predominant signal
      transduction pathway of PDGF which is overexpressed in activated HSC. This study
      investigated the cleavage activity of hammerhead ribozyme targeting PDGFR-beta
      mRNA in HSC and the effect on biological characteristics of HSC. METHODS:
      Expression vector of anti-PDGFR-beta ribozyme was constructed and transfected
      into rat activated HSC with lipofectamin. The positive cell clones were gained by
      G418 selection. The expression of PDGFR-beta, alpha-smooth muscle actin, and
      typeI and type III collagen were detected by using Northern blot, Western blot
      and immunocytochemical staining, respectively. The cell proliferation was
      determined with MTT colorimetric assay. The cell apoptosis was analyzed by using
      flow cytometry, acridine orange fluorescence vital staining and transmission
      electron microscopy. RESULTS: The expression of PDGFR-beta at mRNA and protein
      level was markedly reduced in ribozyme-transfected HSC by 49% - 57% (P < 0.05 -
      0.01). The proliferation and alpha-smooth muscle actin expression of ribozyme
      transfected HSC were significantly decreased (P < 0.05 - 0.01), and the type I
      and type III collagen synthesis were also reduced (P < 0.01). In addition, the
      proliferative response of ribozyme-transfected HSC to PDGF BB was significantly
      inhibited. Otherwise, the apoptotic cells were significantly increased in
      ribozyme-transfected HSC (P < 0.01), and typical apoptotic cells could be found
      under transmission electron microscopy. CONCLUSIONS: The anti-PDGFR-beta ribozyme
      effectively cleaved the target RNA and significantly inhibited its expression,
      which blocked the signal transduction of PDGF at receptor level, inhibited HSC
      proliferation and collagen synthesis, and induced HSC apoptosis. These results
      suggest that inhibiting PDGFR-beta expression of HSC may be a new target for the
      therapy of liver fibrogenesis, and ribozyme may be a useful tool for inhibiting
      PDGFR-beta expression.

PMID- 15978206
TI  - Surgical intervention for advanced valvular heart disease in 227 cases.
AB  - BACKGROUND: Although the results of surgical treatment in cardiac valve disease
      continue to improve, the postoperative mortality rate and the rate of
      complications in patients with advanced valvular heart disease (AVHD) are still
      very high. We did this retrospective study to summarize the surgical experience
      of heart valve replacement for patients with AVHD and discuss effective ways to
      improve the surgical outcome. METHODS: From January 1994 to October 2003,
      surgical procedures of heart valve replacement were performed on 227 (136 men and
      91 women) patients with AVHD in our Department of Cardiothoracic Surgery. The
      clinical data of all patients were collected and analysed. Patients' age ranged
      from 10 years to 77 years. In preoperative cardiac function grading, 157 cases
      were NYHA III and 70 cases NYHA IV. Fifty-one patients had had cardiac
      operations. The ultrasonic cardiac graphs showed that 145 patients suffered from
      moderate or severe pulmonary hypertension and 73 had combined giant left
      ventricle. Mitral valve replacement was performed in 32 cases, aortic valve
      replacement in 90, tricuspid valve replacement in 1, combined mitral and aortic
      replacement in 103 and combined mitral and tricuspid replacement in 1. Nineteen
      patients also received surgical corrections for other minor abnormalities during
      the operations. A logistic model was established to evaluate the influence of
      perioperative factors on the mortality rate. RESULTS: The operative mortality
      rate was 13.2% (30/227). The main causes of death included multiple organ
      dysfunction syndrome (MODS), low cardiac output syndrome and ventricular
      fibrillation. From the results of the binary noncounterpart multivariate logistic
      regression, the following statistically significant factors were found to
      influence the operative mortality rate: redo operation, age >/= 55 years,
      preoperative NYHA cardiac function grading, extracorporeal circulation time >/=
      120 minutes and postoperative usage of GIK (glucose, insulin and potassium)
      solution. All factors were risk ones except postoperative application of GIK. The
      Hosmer-Lemeshow goodness of fit coefficient of this model was 0.976. CONCLUSIONS:
      The risk factors associated with postoperative mortality rate in the patients
      with AVHD were redo operation, age >/= 55 years, preoperative NYHA cardiac
      function grading and extracorporeal circulation time >/= 120 minutes.
      Postoperative usage of GIK acted as a kind of metabolic therapy and will improve
      the recovery for patients with AVHD. Active perioperative management and care
      will play a very important role in reducing the operative risk and improving the
      short term outcome of surgical treatment for the patients with AVHD.

PMID- 15978207
TI  - Analysis of oral glucose tolerance test in pregnant women with abnormal glucose
      metabolism.
AB  - BACKGROUND: Due to the controversy of the oral glucose tolerance test (OGTT),
      diagnostic criteria for gestational diabetes mellitus (GDM) in the world and
      researches on GDM remain undeveloped in China. American Diabetes Association
      recently recommended the clinicians to diagnose GDM by OGTT results without the
      third-hour glucose value. This new criteria has not been used in China. Research
      on the value and sensitivity of the criteria in detecting GDM is rare. The aim of
      our study is to analyze the characteristics of OGTT in Chinese women with GDM or
      gestational impaired glucose tolerance (GIGT) and to evaluate the effect of
      omission of the third-hour plasma glucose (PG) level in OGTT on the sensitivity
      of diagnosing GDM and GIGT, and the relationship between PG values of 50 g GCT or
      OGTT and insulin therapy. METHODS: A retrospective analysis was performed on
      medical records of 647 cases with GDM from January 1, 1989 to December 31, 2002,
      and 233 with GIGT. Among 647 cases of GDM, 535 cases were diagnosed by 75 g OGTT.
      All OGTT results including 535 cases of GDM and 233 patients with GIGT were
      evaluated. RESULTS: There were 112 cases of GDM diagnosed by elevated fasting PG
      (FPG) without OGTT performed. Of 535 cases of GDM diagnosed by OGTT, 49.2%
      (263/535) women had FPG value >/= 5.8 mmol/L; 90.1% (482/535) women with 1-hour
      PG values >/= 10.6 mmol/L; 64.7% (359/535) with 2-hour PG levels >/= 9.2 mmol/L.
      There were only 114 cases (21.3%) with abnormal 3-hour PG levels among 535 women
      with OGTT. Among those with abnormal 3-hour PG level, 49.1% (56/114) had abnormal
      glucose values in the other three points of OGTT, and 34.2% (39/114) with two
      other abnormal values of OGTT. Our study showed that omission of the 3-hour PG of
      OGTT only missed 19 cases of GDM and they would be diagnosed as GIGT. Among the
      233 women with GIGT, only 4 cases had abnormal 3-hour PG. So, omission of the
      third-hour glucose value of OGTT only resulted in failure to diagnose 3.6%
      (19/535) women with GDM diagnosed by OGTT, which means 2.9% (19/647) of all the
      GDM and 1.7% (4/233) of GIGT in Chinese women. PG levels >/= 11.2 mmol/L
      following 50 g GCT was highly associated with GDM necessitating insulin therapy
      (75.4%). An elevated FPG level was also associated with insulin therapy (59.7%).
      CONCLUSIONS: Omission of the third-hour glucose tolerance test value still yield
      a higher sensitivity in diagnosing GDM and GIGT. In Chinese women, it is
      practicable to omit third-hour post-glucose ingestion value of the OGTT in
      Chinese women. PG levels >/= 11.2 mmol/L following 50 g GCT mostly indicates that
      the requirement of insulin therapy.

PMID- 15978208
TI  - Gene expression of fibrinolytic factors urokinase plasminogen activator and
      plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage
      with disc displacement.
AB  - BACKGROUND: The urokinase plasminogen activator system is believed to play an
      important role in degradation of the extracellular matrix associated with
      cartilage and bone destruction; however its precise roles in temporomandibular
      disorders have not yet been clarified. The aims of this study were to investigate
      the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA)
      and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of
      rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the
      relationship between fibrinolytic activity and cartilage remodeling. METHODS:
      Disc displacement of right joints was performed in 36 of 78 rabbits under
      investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks
      after surgery, respectively. The right joints of these animals were harvested and
      processed for the examination of mRNA expression of uPA and PAI-1 in articular
      cartilage using in situ hybridization techniques. RESULTS: The expression of uPA
      and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to
      hypertrophic zone and mineralized zone, while no hybridizing signals were shown
      in proliferative zone and superficial zone in control rabbits. The most striking
      was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at
      the onset of cartilage degeneration. The strongest hybridizing signals for uPA
      and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the
      expression of uPA and PAI-1 began to decrease and reached nearly normal level at
      12 weeks. CONCLUSIONS: The expression of the uPA/PAI-1 system coincides with the
      pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be
      one of the essential mediators in articular cartilage remodeling.

PMID- 15978209
TI  - Research on airway inflammation: present status in Mainland China.

PMID- 15978210
TI  - Toxoplasmosis researches in China.

PMID- 15978211
TI  - Application of functional MRI in epilepsy.
AB  - OBJECTIVE: To review the recent development of functional MRI application in
      epilepsy. DATA SOURCES: Both Chinese and English language literatures were
      researched using MEDLINE/CD ROM (1996 - 2005) and the Chinese Biomedical
      Literature Disk (1996 - 2005). STUDY SELECTION: Published articles about
      functional MRI application and epilepsy were selected. DATA EXTRACTION: Data were
      mainly extracted from 38 articles which are listed in the reference section of
      this review. RESULTS: fMRI can be used to localize seizure foci through detecting
      these cerebral hemodynamic changes produced by epileptiform discharges. EEG
      triggered fMRI, which has higher spatial and temporal resolution, helps to detect
      the spatiotemporal pattern of spike origin and propagation, and define
      localization of the epileptogenic focus. fMRI is also useful in language and
      memory cognitive function assessment and presurgical assessment of refractory
      epilepsy. Atypically distributed cognitive function areas can be detected by
      fMRI, because of cortical language and memory areas reorganization during long
      term epileptic activity in patients with epilepsy. CONCLUSIONS: fMRI technique
      plays a very important role in cognitive function and presurgical assessment of
      patients with epilepsy. It is meaningful for understanding pathogenesis of
      epilepsy.

PMID- 15978212
TI  - Rosiglitazone improves post-infarction left ventricular contractile function in
      rats.

PMID- 15978213
TI  - Effects of cilazapril on endothelial cell function and fibrinolysis system in
      atrial fibrillation.

PMID- 15978214
TI  - Application of serum surface-enhanced laser desorption/ionization proteomic
      patterns in distinguishing lung cancer patients from healthy people.

PMID- 15978215
TI  - Effects of irbesartan on the expression of matrix metalloproteinase-2/tissue
      inhibitor of metalloproteinase-2 in streptozotocin-induced diabetic rat kidney.

PMID- 15978216
TI  - Subcutaneous abscess caused by Pasteurella multocida in a patient due to a cat
      bite.

PMID- 15978217
TI  - Resection of tracheal tumor under cardiopulmonary bypass: a case report.

PMID- 15978218
TI  - Medical imaging findings in Cobb syndrome: two case reports.

PMID- 15978219
TI  - Disseminated Penicillium marneffei infection in acquired immunodeficiency
      syndrome: a case report.

PMID- 15978220
TI  - Pittsburgh experience with lower urinary tract botulinum toxin A injection.

PMID- 15978221
TI  - Alpha-blockers in the management of acute urinary retention: results of a double
      blind, placebo-controlled study.

PMID- 15978222
TI  - Fact or fiction: what do the benign prostatic hyperplasia data tell us?
AB  - Benign prostatic hyperplasia (BPH) is the most common benign neoplasm in men. Our
      understanding of this condition has improved greatly over the years and recent
      advances have changed our approach to management. At the end of the 19th century,
      prostatic enlargement was treated effectively by bilateral orchidectomy.
      Unsurprisingly, this treatment option never gained widespread popularity. Less
      than 10 years ago, surgery and watchful waiting were the only considered
      treatment options for BPH. We now have a number of medical therapies and
      minimally invasive treatment options available that can effectively manage lower
      urinary tract symptoms secondary to benign prostatic obstruction. However, with
      increased choice comes the increased need for clarity in selection and
      application of these various treatment options. In the current environment of
      evidence-based clinical practice, awareness and interpretation of data from the
      numerous studies is paramount. The lessons learned from these trials should be
      reflected clearly in our practice, with clinical management based on fact, not
      fiction. In this review, we critically assess the available data and
      understanding of the management of BPH.

PMID- 15978223
TI  - Symptom scores: mumbo jumbo or meaningful measures?
AB  - Instruments designed to assess the severity of lower urinary tract symptoms have
      become a routine component of the diagnostic evaluation of men with benign
      prostatic hyperplasia (BPH). Several validated tools have been developed to this
      end, including the International Prostate Symptom Score, which is used most
      commonly today. Despite attempts to correlate symptom score severity with
      commonly measured objective parameters of BPH, no clear relationships have been
      found. The reason for this is likely multifactorial and suggests a complex
      relationship among subjective and objective variables. However, symptom scores
      show a good correlation with the patient's perception of quality of life and
      degree of bother. This is critical because the decision to treat should be
      largely based on these subjective variables. Moreover, symptom scores have been
      shown to represent a meaningful endpoint in assessing treatment response in
      clinical studies.

PMID- 15978224
TI  - Lasers for lower urinary tract symptoms secondary to benign prostatic
      hyperplasia: when is the fuss worth it?
AB  - In the recent past, several endoscopic procedures using laser technology have
      evolved for the treatment of benign prostatic hyperplasia. The term "laser
      treatment of the prostate" comprises a variety of different application systems,
      different laser wavelengths, and different surgical techniques to eliminate
      bladder outlet obstruction. The aim of laser prostatectomy is to be less invasive
      than transurethral electroresection, but equally effective. Promising short-term
      results led to a booming laser decade in the 1990s, stimulating the development
      of several devices. However, the emergence of medium-term data has shown that
      some of these techniques did not stand the test of time due to the lack of long
      term efficacy, unacceptable morbidity, and high retreatment rates. Nevertheless,
      the results of transurethral resection of the prostate are challenged by some of
      the newer laser devices, putting the so-called "gold standard" into question.

PMID- 15978225
TI  - Acute urinary retention in men: the risks and outcomes with medical therapy.
AB  - This paper is restricted to the discussion of the relatively modern disorder of
      sudden painful inability to urinate in older men. It was not a common medical
      problem until the 19th century when, in developed countries, male life expectancy
      increased to beyond 60 years; it remains an uncommon problem in those developing
      countries where male life expectancy remains low, particularly in some sub
      Saharan African countries where male life expectancy is only 44.8 years.

PMID- 15978226
TI  - Diagnosis and treatment of primary bladder neck obstruction in men.
AB  - Although primary bladder neck obstruction was first described approximately 70
      years ago, it is within the past 20 years that the symptoms, signs, and methods
      of diagnosis and treatment have been elucidated. This article describes its
      typical presenting symptoms and signs that commonly may lead to a missed
      diagnosis for a number of years in many cases. The treatments typically available
      are pharmacologic or surgical. Unfortunately, most treatments have not been
      studied in prospective, randomized trials to assess true efficacy. The natural
      history of this disorder, both treated and untreated, demands much further study
      to determine its effect on progression of symptoms and bladder and renal
      function.

PMID- 15978227
TI  - Antinanobacterial therapy for men with chronic prostatitis/chronic pelvic pain
      syndrome and prostatic stones.

PMID- 15978228
TI  - Granulomatous Prostatitis Linked to HLA-DRB1*1501.

PMID- 15978229
TI  - Post-ejaculatory Pain.

PMID- 15978230
TI  - CD4 and CD8 T-lymphocyte Recognition.

PMID- 15978231
TI  - Prostatitis: epidemiology of inflammation.
AB  - Approximately 8 million prostatitis-related outpatient visits per year have been
      reported worldwide. Only a small percentage presents with bacterial prostatitis.
      Chronic pelvic pain syndrome/prostatodynia is a frustrating disease for patients
      and caregivers. This paper is an attempt to analyze causes and types of
      inflammation and to determine if inflammation may have an impact on treatment and
      outcome. Is inflammation even a relevant factor in the diagnosis of chronic
      pelvic pain syndrome? Do we need to begin to look for different factors involved
      in the development of this often crippling disease?

PMID- 15978232
TI  - Saw palmetto and finasteride in the treatment of category-III prostatitis/chronic
      pelvic pain syndrome.
AB  - Chronic nonbacterial prostatitis/chronic pelvic pain syndrome is a common entity
      for which a standardized management has not been established. Patients often have
      a significant symptom complex and impact on quality of life, but very little is
      known about the efficacy of second- and third-line treatments, such as the use of
      herbal supplements. Many treatments studied in recent literature include
      antibiotics, alpha-blockade, anti-inflammatory agents, and cognitive behavioral
      interventions such as biofeedback and psychotherapy.

PMID- 15978233
TI  - Multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome.
AB  - Category III chronic prostatitis/chronic pelvic pain syndrome is a syndrome
      rather than a specific disease and the cause can be multifactorial. In clinical
      practice, monotherapy often has proven ineffective. Multimodal therapy, which
      sequentially or simultaneously can address infection, inflammation, and
      neuromuscular spasm appears to have the greatest potential for symptom
      improvement, especially in patients with longstanding symptoms.

PMID- 15978234
TI  - Role of bacteria in chronic prostatitis/chronic pelvic pain syndrome.
AB  - Throughout the past century, we have refined our understanding of prostatitis,
      moving from using a primarily clinical definition to considering it as a complex
      inflammatory condition. The inconsistency in identifying uropathogens in patients
      with symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has
      led to controversy in therapeutic management. There is compelling evidence that
      the normal prostate has minimal inflammation and no bacteria. Clinicians using
      the Meares/Stamey criteria identified uropathogens localized to the prostate in
      only 6% to 8% of CP/CPPS patients. This suggests that bacteria may have a role in
      less than 10% of men with CP/CPPS. That some patients respond to antimicrobials
      could suggest that eradication of bacteria reduces symptoms. However, the
      beneficial effect of antimicrobial drugs may not be due to their antibacterial
      action, but to their anti-inflammatory action. The normal prostate shows minimal
      inflammation, but only 50% of CP/CPPS patients exhibit prostatic leukocytosis.
      Prudence demands that we examine the function of the white blood cells--the
      cytokines produced. Several basic science advances allowed new avenues of
      research regarding the detection of molecular evidence of causative uropathogens.
      New research brings new controversy and unexpected findings, but further refines
      our understanding of the immune system and the CP/CPPS disease process.

PMID- 15978235
TI  - Prostatitis and serum prostate-specific antigen.
AB  - Prostatitis is an inflammatory condition of the prostate and has been divided
      into four categories according to the National Institutes of Health
      classification. This article reviews the various types of prostatitis and their
      effect on serum prostate-specific antigen levels. Various proposed mechanisms of
      this elevation include leakage of prostate-specific antigen (PSA) into the blood
      stream, hypervascularity, and altered vascular permeability secondary to
      inflammation. Acute prostatitis can lead to an increase in PSA, which usually
      returns to normal levels with appropriate antibiotics within 1 to 3 months.
      Patients with chronic prostatitis have a less well-defined decrease in PSA after
      an antibiotic course. Whether a course of antibiotics prior to biopsy increases
      the yield has not been well established. Asymptomatic inflammation of the
      prostate has been recognized to be an important confounding factor in patients
      with an elevated PSA. Inflammation has been proposed to be a precursor of
      prostate adenocarcinoma.

PMID- 15978238
TI  - Etiology and pathogenesis of periodontal diseases.
AB  - The two most prevalent and most investigated periodontal diseases are dental
      plaque-induced gingivitis and chronic periodontitis. The last 10 to 15 years have
      seen the emergence of several important new findings and concepts regarding the
      etiopathogenesis of periodontal diseases. These findings include the recognition
      of dental bacterial plaque as a biofilm, identification and characterization of
      genetic defects that predispose individuals to periodontitis, host-defense
      mechanisms implicated in periodontal tissue destruction, and the interaction of
      risk factors with host defenses and bacterial plaque. This article reviews
      current aspects of the etiology and pathogenesis of periodontal diseases.

PMID- 15978236
TI  - Therapeutic options for chronic prostatitis/chronic pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome continues to pose a treatment
      challenge for urologists. Most commonly prescribed medications, such as
      antibiotics, a-blockers, androgen inhibitors, and anti-inflammatory agents, have
      been shown to help some patients. However, the efficacy and durability of such
      treatments lack consistency among men suffering from this disorder. The rationale
      for such treatments is described in this article, along with possible
      explanations for the apparent shortcomings. Also included is a brief summary of
      alternative therapies, which are growing in popularity among patients and gaining
      acceptance in our medical communities.

PMID- 15978239
TI  - Epidemiology and risk factors of periodontal diseases.
AB  - Periodontal diseases are chronic inflammatory disorders encompassing destructive
      and nondestructive diseases of the periodontal supporting tissues of teeth.
      Gingivitis is a nondestructive disease ubiquitous in populations of children and
      adults globally. Aggressive periodontitis is characterized by severe and rapid
      loss of periodontal attachment often commencing at or after the circumpubertal
      age and is more prevalent among Latin Americans and subjects of African descent,
      and least common among Caucasians. Chronic periodontitis is a common disease and
      may occur in most age groups, but is most prevalent among adults and seniors
      world-wide. Approximately 48% of United States adults have chronic periodontitis,
      and similar or higher rates have been reported in other populations. Moderate and
      advanced periodontitis is more prevalent among the older age groups, and rates of
      70% or more have been reported in certain populations. Chronic and aggressive
      periodontitis are multifactorial diseases caused primarily by dental plaque
      microorganisms, and with important modifying effects from other local and
      systemic factors. The study of the significance of demographic, environmental,
      and biologic variables is important for risk assessment and the control of
      periodontal diseases.

PMID- 15978240
TI  - Systemic effects of periodontal diseases.
AB  - A number of studies suggest an association between periodontal disease and
      cardiovascular disease, pulmonary disease, diabetes,and pregnancy complications.
      Presently, the data must be regarded as preliminary. Additional large-scale
      longitudinal epidemiologic and interventional studies are necessary to validate
      these associations and to determine whether the associations are causal. The goal
      of this article is to review the history of this concept, describe the
      biologically plausible circumstances that may underlie these potential
      associations, and provide a summary of the published literature that supports or
      refutes them.

PMID- 15978242
TI  - Prevention of periodontal diseases.
AB  - The ultimate goal of periodontal disease prevention is to maintain the dentition
      over a lifetime in a state of health, comfort, and function in an aesthetically
      pleasing presentation. This article focuses on primary and secondary periodontal
      disease prevention as they relate to gingivitis and periodontitis. Risk
      assessment, mechanical plaque control, chemical plaque control, current clinical
      recommendations for optimal prevention, and future preventive strategies are
      discussed.

PMID- 15978243
TI  - Nutrition and periodontal disease.
AB  - This article discusses general concepts of nutrition and provides an overview of
      the current understanding of the relationship between nutrition and periodontal
      disease.

PMID- 15978241
TI  - Diagnostic biomarkers for oral and periodontal diseases.
AB  - This article provides an overview of periodontal disease diagnosis that uses
      clinical parameters and biomarkers of the disease process.This article discusses
      the use of biomarkers of disease that can be identified at the tissue, cellular,
      and molecular levels and that are measurable in oral fluids such as saliva and
      gingival crevicular fluid. Biomarkers identified from these biologic fluids
      include microbial, host response, and connective tissue-related molecules that
      can target specific pathways of local alveolar bone resorption. Future prospects
      for oral fluid-based diagnostics that use micro-array and microfluidic
      technologies are presented.

PMID- 15978244
TI  - Nonsurgical approaches for the treatment of periodontal diseases.
AB  - This article reviews nonsurgical approaches for the management of periodontal
      diseases. A brief review of the pathogenesis of periodontitis allows the reader
      to identify the potential points of intervention. Assessment of risk factors for
      periodontitis and the potential for risk reduction are introduced as the first
      part of a three-pronged approach to therapy. Antimicrobial approaches, including
      the use of mechanical therapy, antiseptics, and antibiotics,are described next.
      Host modulatory therapy is addressed as the fi-nal component of the nonsurgical
      approach to periodontal therapy. Clinical applications of these nonsurgical
      options are presented as part of the treatment strategy.

PMID- 15978245
TI  - Periodontal regeneration techniques for treatment of periodontal diseases.
AB  - The ultimate goal of periodontal therapy is the regeneration of structures lost
      to disease. Conventional surgical approaches such as open-flap debridement offer
      only limited regeneration potential.Currently, surgical procedures for
      predictable regeneration of periodontal tissues are being developed, analyzed,
      and employed in clinical practice. This article addresses current trends in
      periodontal regeneration. Various materials/agents such as bone replacement
      grafts, barrier membranes, and biologic modifiers currently used for the
      regeneration of periodontal infrabony and furcation defects are discussed.

PMID- 15978246
TI  - Peri-implantitis.
AB  - The risk of developing peri-implantitis seems to be more pronounced in patients
      with a history of periodontitis. Pretreatment to eliminate periodontal pathogens
      from the patient's oral cavity before dental implant treatment therefore is
      important to reduce the risk of peri-implantitis. Smoking has been shown to be a
      negative risk factor for treatment success. Several protocols have been used in
      the treatment of peri-implantitis. Mechanical infection control following
      surgical flap procedures, particularly in conjunction with antimicrobial therapy,
      is the most successful concept. There is no reliable evidence that suggests which
      intervention is the most effective for treating peri-implantitis. This article
      includes background information on the biology of tissue-destructive
      periodontitis and peri-implantitis to help clinicians interpret the clinical
      manifestation of the risk for peri-implantitis.

PMID- 15978247
TI  - Future treatment and diagnostic strategies for periodontal diseases.
AB  - Many new technologies have been developed or are being developed that could
      enhance the ability to diagnose, predict, and treat periodontitis. Newer
      treatment strategies may allow clinicians to achieve limited or more robust
      regeneration of the periodontium. New or refreshed approaches to disease control
      are being pursued that will benefit those suffering from chronic periodontal
      disease. In addition to novel therapeutics, there has been increasing focus on
      the development of more sensitive and specific diagnostic tests for periodontal
      diseases. Such tests will allow the clinician to determine whether a patient has
      active disease and what sort of attachment loss might be expected if the patient
      is not treated. By developing newer diagnostic tests, it also may be possible to
      detect and monitor active disease during therapy.

PMID- 15978248
TI  - Morphological changes in glaucomatous eyes and the role of TGFbeta2 for the
      pathogenesis of the disease.
AB  - This review summarizes the Ernst H. Barany Prize Lecture given at the XVI.
      meeting 2004 of the International Society of Eye Research in Sydney, Australia.
      The article describes the author's early studies starting with the determination
      of the site of aqueous humour outflow resistance and its regulation through
      ciliary muscle contraction, which were performed in collaborations with Barany.
      It continues with the qualitative and quantitative evaluation of the trabecular
      meshwork (TM) changes seen in different kinds of glaucoma diseases. A comparison
      of correlations between meshwork pathology, IOP, and axon loss in the optic nerve
      between eyes with pseudoexfoliation glaucoma (PEXG) and primary open angle
      glaucoma (POAG) indicates that in the secondary glaucoma (PEXG) optic neuropathy
      is mainly induced by an increase in IOP. In eyes with POAG, the correlations
      point towards a more complex pathogenesis of the disease. Common factors might be
      involved in both the TM and the optic nerve changes. In vitro studies performed
      in cell cultures of human TM cells and optic nerve astrocytes as well as organ
      culture studies of the anterior eye segment indicate that TGFbeta2 might be one
      of the factors involved in the development of POAG. The paper is primarily
      focused on studies performed by the author and complete reference to other
      previous or contemporary studies is therefore not given as the purpose is not to
      present a comprehensive review article.

PMID- 15978249
TI  - Expression and functional evaluation of transient receptor potential channel 4 in
      bovine corneal endothelial cells.
AB  - We previously found that activation of purinergic receptors mobilizes Ca2+ and
      enhances bicarbonate transport in bovine corneal endothelial cells (BCEC). Since
      transient receptor potential channel 4 (TRPC) has been reported to be a candidate
      for capacitative calcium entry (CCE) and receptor operated calcium entry (ROC),
      we examined the expression of TRPC4 and evaluated the potential involvement of
      TRPC4 in CCE or ROC in BCEC. The C-terminus of TRPC4 was fused into the
      glutathione S-transferase (GST) expression vector. The fusion protein GST-TRPC4c
      was induced in bacteria and purified by affinity chromatography. An antibody was
      raised in rabbit by using the purified GST-TRPC4c antigen. In Western blotting,
      the TRPC4 antibody recognized the fusion protein while the pre-immune IgG did
      not. The TRPC4 antibody recognized a band at around 80 kD for membrane proteins
      from both the fresh and cultured BCEC. The pre-immune IgG could not detect bands
      at the same size. Incubation with the TRPC4c antigen abolished the 80 kD band.
      Immunofluorescence using the TRPC4 antibody stained both fresh and cultured BCEC,
      while pre-immune IgG did not. RNAi knocked down the expression of TRPC4 in
      cultured BCEC. Ca2+ entry induced by the purinergic receptor agonist ATP, was
      increased in TRPC4-siRNA transfected cells compared with the scrambled siRNA
      control, while Ca2+ entry induced by store depletion through blocking the
      endoplasmic reticulum Ca2+ pump, did not differ between the siRNA and scrambled
      siRNA-treated cells. Taken together, these results show that TRPC4 protein is
      expressed in the bovine corneal endothelial cells and may be a negative regulator
      in ROC stimulated by purinergic activation, but not by store depletion itself.

PMID- 15978250
TI  - Suppression of Mitf by small interfering RNA induces dedifferentiation of chick
      embryonic retinal pigment epithelium.
AB  - Recent studies indicate a key role of Mitf (microphthalmia-associated
      transcription factor) in the differentiation of the retinal pigment epithelium
      (RPE). To explore transdifferentiation processes, we used small interfering RNA
      (siRNA) targeting Mitf. Transfection of embryonic chick RPE cells with a non
      silencing fluorescein-labelled control siRNA demonstrated a high (84%)
      transfection efficiency. Transfection of Mitf siRNA reduced Mitf synthesis at the
      mRNA and protein levels as analysed by real-time RT-PCR and Western blot. Mitf
      siRNA suppressed the expression of Mitf RNA to 25.0% of the level in control
      cells (P<0.005). The expression of melanosomal matrix glycoprotein 115 (MMP115),
      a marker of differentiated pigment cells, was also markedly suppressed (to 52.2+/
      6.6%) (P<0.0005). Moreover, the expression of Pax6 was increased by Mitf siRNA
      (to 143.5+/-18.0%) (P<0.0005), and induced dedifferentiation of the RPE cells.
      These data suggest siRNA can be an effective gene silencing approach in RPE, and
      reduction of Mitf expression is essential for the dedifferentiation of RPE cells.

PMID- 15978251
TI  - Endostatin modulates VEGF-mediated barrier dysfunction in the retinal
      microvascular endothelium.
AB  - Recent evidence indicates that the anti-angiogenic peptide endostatin may
      modulate some of the vasomodulatory effects of vascular endothelial growth factor
      (VEGF) in the retina, including reduction of blood retinal barrier function
      although it remains uncertain how endostatin promotes endothelial barrier
      properties. The current study has sought to examine how physiological levels of
      endostatin alters VEGF-induced inner BRB function using an in vitro model system
      and evaluation of occludin and ZO-1 regulatory responses. In addition, the
      ability of exogenous endostatin to regulate VEGF-mediated retinal vascular
      permeability in vivo was investigated. Retinal microvascular endothelial cells
      (RMEC's) were exposed to various concentrations of endostatin. In parallel
      studies, RMEC monolayers were treated with vascular endothelial growth factor
      (VEGF165). Vasopermeability of RMEC monolayers and occludin expression were
      determined. Blood retinal barrier integrity was quantified in mouse retina using
      Evans Blue assay following intravitreal delivery of VEGF165, endostatin or a
      VEGF/endostatin combination. Endostatin increased the levels of expression of
      occludin whilst causing no significant change in FITC-dextran flux across the
      RMEC monolayer. Endostatin reversed the effects of VEGF165-enhanced permeability
      between microvascular endothelial cells and induced phosphorylation of occludin.
      Evans Blue leakage from retinas treated with VEGF was 2.0 fold higher than that
      of contra-lateral untreated eyes (P<0.05) while leakage of eyes from endostatin
      treated animals was unchanged. When eyes were injected with a combination of
      VEGF165 and endostatin there was a significant reduction in retinal
      vasopermeability when compared to VEGF-injected eyes (P<0.05). We conclude that
      endostatin can promote integrity of the retinal endothelial barrier, possibly by
      preventing VEGF-mediated alteration of tight junction integrity. This suggests
      that endostatin may be of clinical benefit in ocular disorders where significant
      retinal vasopermeability changes are present.

PMID- 15978252
TI  - SiRNA strategy against overexpression of extracellular matrix in diabetic
      retinopathy.
AB  - Increased synthesis of extracellular matrix (ECM) contributes to the development
      of vascular BM thickening, a prominent abnormality in diabetic retinopathy. RNA
      interference (RNAi) approach was used in this study to examine the effect of
      small interfering RNAs (siRNAs) for their ability to inhibit ECM-specific gene
      overexpression under high glucose condition in rat microvascular endothelial
      cells (RMECs). Four fibronectin (FN)-siRNAs, three collagen IV (Coll IV)-siRNAs,
      and four laminin (LM)-siRNAs, a total of 11 siRNAs were screened. RMECs were
      transfected with 10, 30, or 100 nm of each siRNAs in the presence of 8 microm
      lipofectin and subjected to analysis 72 hr after transfection. In long-term
      studies siRNA-transfected cells were examined after 12 days. Two FN siRNAs, two
      Coll IV siRNAs, and two LM siRNAs significantly reduced the respective target
      expressions. Findings from this study indicate that high glucose-induced abnormal
      expression of BM components may contribute to increased vascular permeability.
      SiRNA may be a useful tool in preventing excess vascular permeability, a
      characteristic feature of early diabetic retinopathy.

PMID- 15978253
TI  - Blood-derived macrophages infiltrate the retina and activate Muller glial cells
      under experimental choroidal neovascularization.
AB  - Inflammation is a major mechanism in the pathogenesis of age-related macular
      degeneration, the most important cause of blindness in the elderly. Previous
      studies have focused on the role of macrophages in regulating the growth of
      pathological new vessels over the retina, called choroidal neovascularization
      (CNV). However, no research has been done to evaluate the role of inflammation as
      a mechanism of vision loss and retinal degeneration in the retina underlying CNV.
      In other neuropathological conditions, hematogenous macrophages and/or resident
      microglia contribute to neurodegeneration. We have combined laser-induced CNV in
      mice and bone marrow transplantation with GFP-labeled bone marrow to determine
      the relative role of recruited blood-derived macrophages versus resident
      microglia in the retina associated with CNV. Using these chimeric mice, we have
      found that many GFP-labeled cells infiltrated the retina underlying CNV but not
      the retina unaffected by CNV. Immunostaining for the cell adhesion molecules VCAM
      1, ICAM 1, and PECAM was strongly upregulated in retinal blood vessels under CNV.
      All GFP-labeled cells were immunoreactive for the macrophage marker F4/80. Most
      (70%) of the F4/80 immunoreactive cells were GFP-labeled under CNV. The density
      of resident microglia did not increase. Most GFP-labeled cells were found in
      close proximity to activated Muller cells. Depleting circulating macrophages with
      clodronic acid diminished the density of F4/80 immunoreactive cells as well as
      the density of pERK immunoreactive Muller cells in the retina under CNV. Thus,
      recruitment of blood-derived macrophages more than resident microglia seems to be
      associated with CNV.

PMID- 15978254
TI  - Long-term glial reactivity in rat retinas ipsilateral and contralateral to
      experimental glaucoma.
AB  - Although glaucoma is known to alter glial reactivity, the long-term effect of
      elevated intraocular pressure (IOP) on glial change has not been fully
      elucidated. This study aimed to examine how chronically elevated IOP induced by
      episcleral vein cauterization (EVC) in unilateral eyes affect reactivities of
      astrocytes and Muller cells of rats in the treated as well as contralateral eyes
      over time. EVC in unilateral eyes of Sprague-Dawley rats were performed to
      produce chronically elevated IOP. Flat mounted retina preparations were made at
      several points until 6 months, which were subjected to immunostaining for glial
      fibrillary acidic protein (GFAP). Retinal homogenates were one- or two
      dimensionally electrophoresed, followed by GFAP immunoblotting. EVC significantly
      increased IOPs up to 27.8 from 13.1 mmHg, which gradually decreased over time. In
      flat mounted retinas, astrocytes lost but Muller cells gained GFAP
      immunoreactivity at 3 days after cauterization. The glial changes were partially
      reversed over time but last even after IOP normalization. In the contralateral
      eyes, similar glial changes gradually appeared at 1 month after EVC and
      thereafter. Immunoblotting demonstrated not only molecular size shifts but also
      alteration of isoelectric focusing of GFAP both in treated and contralateral
      retina as compared with age-matched control retina. EVC led to opposite reactions
      in astrocytes and Muller cells in terms of GFAP immunoreactivity. Late-onset
      glial reactivity also occurred in the contralateral retina.

PMID- 15978255
TI  - Plasma membrane Ca2+-ATPase expression in the human lens.
AB  - The focus of the study was to characterize plasma membrane calcium-ATPase pump
      (PMCA) isoform expression in the human lens and cultured lens epithelial cells as
      a basis for future studies of calcium homeostasis in the lens. Proteins and mRNA
      expression were analysed using Western Immunoblotting and reverse transcription
      polymerase chain reaction (RT-PCR), respectively. Clear human lenses from the
      Kentucky Lions Eye Bank and an immortalized human lens epithelial cell line (HLE
      B-3) were used. RT-PCR products of PMCA1, PMCA2, and PMCA4 primers were detected
      at 429, 557, and 849bp, respectively. All these products were identified as PMCA
      isoforms by sequence analysis. Protein bands at approximately 130, 115, and
      135kDa were detected by Western blot analysis for PMCA1, PMCA2 and PMCA4,
      respectively. PMCA3 was not detected at protein or mRNA level in any human lens
      sample or cell culture, but was detected in the rat brain cortex used as a
      control. Several bands with lower molecular weights, especially for PMCA2, were
      detected in the epithelial samples and probably represent break down products of
      PMCA2. No PMCA proteins or breakdown products were detected in the nuclear or
      cortical fractions from human lenses. PMCA1, 2, and 4 proteins and mRNAs are
      expressed in human lens epithelium and cultured epithelial cells; PMCA3 is not.
      PMCA was not detected at all in the lens fibre cells. The calcium pump must be
      selectively processed, independent of other membrane proteins such as the Na-K
      ATPase pumps, because the distribution of the Na-K-ATPase pump is asymmetrical in
      the epithelium and present throughout the lens whereas the calcium pumps are not.
      The findings of this study provide a basis for further studies to examine the
      role and modulation of PMCA isoforms in calcium homeostasis and in the
      development of cataract.

PMID- 15978256
TI  - Troglitazone reverses the inhibition of nitric oxide production by high glucose
      in cultured bovine retinal pericytes.
AB  - In the retinal microcirculation, there is a basal release of nitric oxide (NO)
      which maintains the retinal blood flow. The proportions of endothelial cells and
      pericytes in the retinal capillaries are almost equal, so pericytes appear to
      play a important role in the regulation of microcirculatory hemodynamics in the
      retina. It has been suggested that the pathogenesis of early diabetic retinopathy
      may involve a reduced bioavailability or diminished production of NO. In this
      study, we investigated the role of troglitazone, a potent agonist of peroxisome
      proliferator activated receptor-gamma (PPARgamma) used for the treatment of
      diabetes, on the NO release and the effect of exposure to high glucose on the
      production of NO in cultured bovine retinal pericytes. Troglitazone significantly
      increased NO production and iNOS expression after 24hr in a dose-and PPARgamma
      dependent manner. Elevation of D-glucose, but not L-glucose, from 5.5 to 30 mm
      for 24 hr decreased NO production, but co-treatment with troglitazone reversed
      high glucose-induced inhibition of NO production as well as iNOS expression. In
      conclusion, high glucose inhibits iNOS expression and subsequently NO synthesis
      in cultured bovine retinal pericytes, and troglitazone restores the NO
      production.

PMID- 15978257
TI  - A new experimental model of glaucoma in rats through intracameral injections of
      hyaluronic acid.
AB  - An experimental model of pressure-induced optic nerve damage would greatly
      facilitate the understanding of the cellular events leading to ganglion cell
      death, and how they are influenced by intraocular pressure and other risk factors
      associated to glaucoma. The aim of the present report was to study the effect of
      a long-term increase of intraocular pressure in rats induced by intracameral
      injections of hyaluronic acid with respect to electroretinographic activity and
      retinal and optic nerve histology. For this purpose, hyaluronic acid was injected
      weekly in the rat anterior chamber of one eye, whereas the contralateral eye was
      injected with saline solution. The results showed a significant decrease of
      oscillatory potentials and a- and b-wave amplitude of the scotopic
      electroretinogram after 3 or 6 weeks of hyaluronic acid administration,
      respectively. These parameters were further reduced after 10 weeks of treatment
      with hyaluronic acid. No significant changes in anterior chamber angle structures
      from hyaluronic acid- and vehicle-injected eyes were observed, whereas a
      significant loss of ganglion cell layer cells and of optic nerve axons were
      detected in animals that received hyaluronic acid for 10 weeks, as compared to
      eyes injected with saline solution. In summary, present results indicate that the
      chronic administration of hyaluronic acid induced a significant decrease in the
      electroretinographic activity and histological changes in the retina and optic
      nerve that seem consistent with some features of chronic open-angle glaucoma.
      Therefore, this could be an experimental model to study the cellular mechanisms
      by which elevated intraocular pressure damages the optic nerve and the retina.

PMID- 15978258
TI  - Birefringence of the primate retinal nerve fiber layer.
AB  - The purpose of this study was to measure the peripapillary retinal nerve fiber
      layer (RNFL) thickness, phase retardation (PR), and depth-resolved birefringence
      (Deltan) of the normal primate eye using Enhanced Polarization-Sensitivity
      Optical Coherence Tomography (EPS-OCT). Both eyes of two rhesus monkeys were
      imaged with EPS-OCT. A multiple incident polarization state nonlinear fitting
      algorithm was used to determine RNFL phase retardation. RNFL thickness (RNFLT)
      was determined from the corresponding EPS-OCT intensity image and phase
      retardation per unit depth (PR/UD, proportional to Deltan) was calculated by
      dividing PR by RNFLT. Peripapillary area maps consisting of pixels uniformly
      distributed along a radius from 0.8 to 1.8 mm from the center of the optic
      nervehead were constructed for RNFLT, PR, and PR/UD. Average PR/UD in the
      superior and inferior quadrants was 18 degrees /100 mivrom (Deltan=4.2 x 10(-4))
      and average PR/UD in the nasal and temporal quadrants was 6.3 degrees /100 microm
      (Deltan=1.5 x 10(-4)). Relative magnitude of PR radial gradient is similar to
      that of RNFLT radial gradient and no radial gradient was observed for PR/UD.
      Polarization-dependent amplitude attenuation per unit depth (PDAA/UD) was 0.02
      rad/100 microm in thick RNFL regions. RNFL birefringence was higher in the
      arcuate bundles compared to nasal and temporal fibers (P=0.001). Birefringence
      was nearly equal in nasal and temporal quadrants. No statistically significant
      (P=0.01) radial gradient of birefringence was observed in any quadrant. RNFL
      birefringence is believed to originate from anisotropic structures within the
      cytoskeleton of the parallel axons. Birefringence differences presented in this
      study cannot be explained by the known axon diameter distribution around the
      optic nervehead and suggest other sources of the birefringence signal including
      neurotubules and neurofilaments.

PMID- 15978259
TI  - Expression of tissue plasminogen activator during eye development.
AB  - Tissue plasminogen activator (tPA) is a serine protease responsible for the
      activation of plasminogen to plasmin as well as extracellular matrix remodeling.
      While tPA is used clinically to treat some retinal disorders and it is expressed
      at low levels in the adult eye, its expression pattern during eye development had
      never been determined. tPA protein is broadly dispersed in the lens placode and
      optic vesicle of the mouse eye and it becomes highly localized to the apical
      surfaces of both the lens pit and the optic cup as they invaginate. In the lens,
      tPA remains at the apical tips of both lens epithelial and fiber cells from the
      lens vesicle stage until birth in the mouse, when it begins to downregulate to
      barely detectable levels in adults. In humans, tPA is found in a similar pattern
      in the lens vesicle and early lens, however, appreciable protein is also detected
      in the cytoplasm of lens epithelial cells until adulthood. In the retina, tPA is
      found at the apical interface between the developing retinal pigmented epithelium
      and neural retina, then begins to downregulate once the photoreceptors have
      differentiated. In conclusion, tPA protein is found in a different pattern in
      embryonic versus adult eyes and may be involved in remodeling of the
      extracellular environment during eye development.

PMID- 15978260
TI  - Dynamic contrast enhanced MRI in patients with diabetic macular edema: initial
      results.
AB  - To assess the ability of dynamic contrast enhanced magnetic resonance imaging
      (DCE-MRI) to detect blood retinal barrier (BRB) damage in patients with diabetic
      macular edema (DME). DCE-MRI with 0.1 mmol Gd-DTPA was used to measure BRB
      permeability in 10 healthy and visually normal subjects and eight patients with
      DME, including five patients with non-clinically significant (NCS) DME and three
      patients with clinically significant (CS) DME. For each subject, the enhancement
      of the MRI signal intensity in the pre-macular vitreous was measured as a
      function of time following contrast injection. A linear regression analysis was
      performed on each subject and the slopes of the contrast enhancement functions
      were compared. The DCE-MRI procedure was well tolerated by all 18 subjects.
      However, in four subjects, excessive eye movements resulted in spurious results.
      Consequently, 78% (14/18) of the subjects provided usable data. The mean slope of
      the control group was not significantly (p>0.05) different from zero (i.e. signal
      intensity in the pre-macular vitreous space was constant as a function of time
      post-contrast injection). For the diabetic patients, the average slope of the
      contrast enhancement function was significantly greater than in the control group
      (p<0.01). Furthermore, for both diabetic sub-groups, the average slopes were
      greater (p<0.05) than that for the control group but not significantly (p>0.05)
      different from each other. This 'proof of concept' study demonstrated that DCE
      MRI detects passive leakage through the BRB in diabetic patients with either NCS
      or CS macular edema. In future studies, DCE-MRI may be useful for early
      quantitative evaluation of drug treatment effects in patients with DME.

PMID- 15978261
TI  - STAT3 activation in response to growth factors or cytokines participates in
      retina precursor proliferation.
AB  - Growth factors and cytokines play an important role in the development of central
      nervous systems including neurons of the retina. However, the molecular pathways
      that trigger cell growth remain unclear in neuronal precursors. In the present
      studies, we used a retinal explant culture system to investigate the response of
      signal transducer and activator of transcription factors (STATs) to extrinsic
      factors during mouse retinal development. Retinas from embryonic and neonatal
      stages showed that STAT3 but not STAT1 was activated in response to ciliary
      neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), fibroblast growth
      factor-1 (FGF1), fibroblast growth factor-2 (FGF2), epidermal growth factor
      (EGF), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) in distinct
      patterns. STAT3 activation was detected in the outermost retina layer in response
      to CNTF, LIF, FGF1, and IFN-alpha 24 hr after stimulation in postnatal day 1
      (PN1) explants, but not FGF2, EGF, IFN-gamma, and retinoic acid (RA). Cytokine
      stimulation increased the number of cells incorporating BrdU and the labelled
      cells co-localized with phosphorylated STAT3, indicating that STAT3 may play an
      essential role in coupling extrinsic factors to retina precursor cell (RPC)
      proliferation. Furthermore, persistent expression of two neural precursor
      markers, Hes1 and Otx2 was detected in outer retinal layers and correlated with
      STAT3 activation by CNTF, suggesting that STAT3 activation may play a critical
      role in stimulating mitotic precursors. These results strongly support a model
      that STAT3-mediated signalling regulates precursor populations during mouse
      retina development.

PMID- 15978262
TI  - Myosin VI is required for normal retinal function.
AB  - Different unconventional myosins have been shown to play important roles in
      sensory function, including vision. We investigated the role of myosin VI by
      examining the retinas of mice carrying a null mutation in the myosin VI gene.
      Myosin VI was found to be present in the photoreceptor and RPE cells of normal
      retinas. In the absence of myosin VI, the amplitudes of the a- and b-waves of the
      electroretinogram were reduced, although there was not photoreceptor cell loss
      and retinal anatomy appeared normal. Our results indicate that myosin VI is
      required in photoreceptor cells for normal retinal electrophysiology.

PMID- 15978263
TI  - Role of nitric oxide and protein kinase C in the tachyphylaxis to vasopressin in
      rat aortic rings.
AB  - The contribution of endothelium-derived mediators and protein kinase C in the
      tachyphylaxis to arginine vasopressin (AVP) was assessed in the rat aorta.
      Endothelium-intact (E+) and denuded rings (E-) obtained from the rat thoracic
      aorta were exposed to three administrations of a supramaximal concentration of
      AVP (100 nM), lasting 20 min and 45 min apart. N-Omega-nitro-L-arginine (NNLA), a
      non-selective inhibitor of all isoforms of NO synthase, and AMT, a selective
      inhibitor for the inducible (iNOS) and neuronal (nNOS) isoforms, diminished the
      tachyphylaxis to AVP significantly in both E+ and in E- rings. No iNOS could be
      detected by Western blots in freshly isolated rings or in rings exposed to AVP,
      despite a strong signal in rings isolated from LPS-treated rats, while nNOS could
      be constitutively detected. Inhibition of prostaglandins or epoxyeicosatrienoic
      acids (EETs) synthesis by diclofenac or clotrimazole, respectively, had no effect
      on tachyphylaxis while combination of these agents diminished tachyphylaxis in E+
      only. Combination of NNLA, diclofenac and clotrimazole blocked completely the
      tachyphylaxis. Inhibition of PKC by either chelerythrine or bisindolylmaleimide I
      HCl (BisI) led to a significant diminution of AVP tachyphylaxis only in E-.
      Activation of PKC with phorbol-12-myristate-13-acetate (PMA) simulated
      tachyphylaxis to AVP in E- only, effect blocked by the NO donor, SNP. In
      conclusion, NO produced from constitutive nNOS present in vascular smooth muscle
      cells participates in tachyphylaxis to AVP. PKC is involved in this tachyphylaxis
      only in E- rings, the presence of NO probably diminishing the effects of this
      kinase.

PMID- 15978264
TI  - Differential effects of ethanol ingestion on somatostatin content, somatostatin
      receptors and adenylyl cyclase activity in the frontoparietal cortex of virgin
      and parturient rats.
AB  - Chronic ethanol ingestion decreases the number of somatostatin (SRIF) receptors
      in the rat frontoparietal cortex and female sex hormones modulate the effects of
      ethanol in the brain. Therefore, we investigated the differential effects of
      ethanol consumption on the SRIFergic system in the frontoparietal cortex of
      virgin and parturient rats given ethanol in their drinking water before and
      during gestation. In parturient rats, ethanol consumption decreased the density
      of SRIF receptors (25%, p<0.01 vs control parturient group) whereas the SRIF-like
      immunoreactivity (SRIF-LI) content was increased (140%, p<0.01). In virgin rats,
      ethanol ingestion decreased the density of SRIF receptors (42%, p<0.01) more than
      in alcoholic parturient rats. SRIF-LI levels were unaffected. The inhibitory
      effect of SRIF on basal and forskolin-stimulated adenylyl cyclase was
      significantly lower in alcoholic virgin rats as compared to alcoholic parturient
      rats. No differences in the levels of the G inhibitory (Gi) alpha1 and Gialpha2
      proteins were observed among the experimental groups. These results suggest that
      gestation may confer partial resistance to the ethanol-induced effect on the
      SRIFergic system.

PMID- 15978265
TI  - Serum BAP as the clinically useful marker for predicting BMD reduction in
      diabetic hemodialysis patients with low PTH.
AB  - With decrease of serum PTH in hemodialysis (HD) patients, other factors besides
      parathyroid hormone (PTH) become important in regulating bone metabolism. We
      investigated which serum bone metabolic marker is the best to predict the bone
      mineral density (BMD) reduction in HD patients with serum PTH<180 pg/ml. The bone
      formation markers, bone alkaline phosphatase (BAP), intact osteocalcin (OC), and
      N-terminal propeptide of type I collagen (PINP), and the bone resorption markers,
      deoxypyridinoline (DPD), pyridinoline (PYD), and beta-crossLaps (beta-CTx) were
      measured in serum from 137 HD patients. BMD of all patients was measured twice,
      approximately 1.5 years before and 1.5 years after measurement of their markers
      of bone metabolism. In all 137 HD patients, serum BAP was the only marker
      significantly higher in those with BMD reduction than in those without. In 42
      diabetes mellitus (DM) HD patients with serum PTH<180 pg/ml, hypothetically low
      bone turnover state, serum BAP was again the only marker to discriminate those
      with BMD reduction from those without. At serum PTH<60 pg/ml, serum BAP retained
      tendency toward higher value. These findings suggest that serum BAP might be the
      most sensitive to identify small changes of bone metabolism in low bone turnover
      state. Retrospective study confirmed the usefulness of serum BAP in clinical
      practice by significantly higher values in those with bone loss at PTH<180 pg/ml
      even in under routine sample handling. In conclusion, serum BAP is a clinically
      useful bone formation marker to predict the BMD reduction in DM HD patients with
      low level of PTH.

PMID- 15978266
TI  - The effect of repeated acute mental stress on habituation and recovery responses
      in hemoconcentration and blood cells in healthy men.
AB  - Acute mental stress elicits hemoconcentration and polycytosis. We investigated
      whether haematological response to repeated acute mental stress would habituate
      and be sustained 45 min and 105 min after stress. Twenty-four men underwent a 13
      min stressor three times, one week apart; hematological variables were measured
      at week one and three. Hematocrit, hemoglobin, leukocytes, lymphocytes,
      erythrocytes, and thrombocytes all increased from rest to immediately post-stress
      (p's<.001). After 105 min of recovery, leukocytes and platelets both were higher,
      and hematocrit, hemoglobin, lymphocytes, and erythrocytes were all lower than at
      rest (p's<.001 to <.05). At all time points, hematocrit (p=.005) and erythrocytes
      (p=.006) were lower at week three than at week one. In contrast to an attenuation
      in systolic blood pressure increase from rest to immediately post-stress
      (p<.001), and in cortisol recovery from immediately post-stress to 45 min post
      stress (p<.001), the magnitude of change in hemoconcentration and cell counts in
      stress and recovery experienced no habituation. Adjustment for stress-induced
      plasma volume shift altered findings: Elevated leukocytes post-stress persisted
      at 105 min (p<.001); any changes in lymphocytes became insignificant;
      erythrocytes decreased from rest to post-stress (p<.001) to increase again during
      recovery (p's<.05); platelets increased linearly between rest and 105 min of
      recovery (p=.005). We conclude that the magnitude of changes in hemoconcentration
      and blood cells during acute mental stress and recovery failed to habituate to
      stress repeats and, in part, sustained up to 105 min. Plasma volume shift
      accompanying stress affects the time course of stress polycytosis.

PMID- 15978267
TI  - An application of the QM-QSAR method to predict and rationalize lipophilicity of
      simple monomers.
AB  - OBJECTIVES: The goal of this study is to develop a model used to predict
      octanol/water partition coefficients (log P(o/w)) values for a variety of
      potential dental materials. In this way, a primary consideration for potential
      toxicity and a rough estimate of solubility in various environments can be
      obtained. METHOD: The AM1 semiempirical quantum mechanical method (in AMPAC) was
      used to compute chemical data for all compounds in the study. CODESSA then
      imported the chemical information from AMPAC and computed a large set of
      informational descriptors. A quantitative structure activity relationship (QSAR)
      model was derived correlating experimental results from a training set of
      molecules with certain of the descriptors computed above. RESULTS: A training set
      of 92 molecules was used to derive the QSAR model and three descriptors were
      obtained: the molecular surface area, the total dipole moment of the molecule,
      and FPSA-3 (fractional atom charge weighted partial positive surface area).
      Various quality indicators were also computed and all fell within acceptable
      ranges: R(2)=0.945; adjusted R(2)=0.943; R(cv)(2)=0.940; variance inflation
      factors (VIF) for the descriptors above are 1.116, 1.044, and 1.162,
      respectively. SIGNIFICANCE: This QSAR model can be used to accurately and rapidly
      predict log P(o/w) values for a wide variety of small organic molecules,
      including potential dental monomers.

PMID- 15978268
TI  - Adverse effects of human pulps after direct pulp capping with the different
      components from a total-etch, three-step adhesive system.
AB  - OBJECTIVES: The objective was to evaluate the response of human pulps capped with
      different components from a total-etch three-step adhesive system. METHODS:
      Direct pulp capping was performed in 25 caries-free human premolars scheduled for
      extraction due to orthodontic treatment. The teeth were randomly divided in five
      groups, and capped with the following materials: Group 1-acid+primer+adhesive
      were used as recommended; Group 2-only primer was applied; Group 3-only bonding
      resin (light-cured for 10s); Group 4-only composite resin (light-cured for 40s);
      Group 5-calcium hydroxide. After capping, all teeth were restored with ScotchBond
      Multi Purpose Plus and Z-100 was placed incrementally. After 60 days, the teeth
      were extracted and processed for light microscopic examination (H/E) according to
      a histological score system. These were subjected to non-parametric tests
      (alpha<0.05). RESULTS: Overall, the histological features showed that groups 1-4
      were quite similar and inferior to group 5. In groups 1-4 the pulp response
      varied from acute inflammatory cell infiltrate with varying degrees to necrosis.
      The groups 3 and 4 showed a trend towards better pulp response, since a normal
      connective tissue could be observed in more than half of the sample. All teeth
      from group 5 showed normal connective tissue below an amorphous dentin bridge.
      SIGNIFICANCE: Adhesive components (primer or adhesive) as well as a composite
      should be avoided for pulp capping. Ca(OH)(2) should be the first choice for pulp
      capping.

PMID- 15978269
TI  - The effect of different light-curing units on fatigue behavior and degree of
      conversion of a resin composite.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of different
      light-curing units and irradiation modes on the mechanical fatigue strength and
      degree of conversion of a restorative resin composite. METHODS: Conventional
      halogen, plasma arc and blue LED light-curing units were used for polymerization
      of a resin composite (Tetric) Ceram, Ivoclar, Vivadent, Liechtenstein). Initial
      fracture strength (FS) and flexural fatigue limit (FFL) as well as degree of
      conversion (DC) were measured. The FFL was determined under cyclic loading for
      10(5) cycles in terms of a staircase approach. The specimens were stored for 14
      days in 37 degrees C distilled water prior to testing. The curing efficiency was
      observed with Fourier transform infrared micromultiple internal reflectance
      spectroscopy. The measurements were carried out at 0.5 and 2.5 mm distance from
      the directly irradiated surface after 14 days storage in dark and dry conditions
      at 37 degrees C. RESULTS: The highest FS, FFL and DC were observed from high
      energy curing devices and from extended curing intervals. The conventional
      halogen light exhibited the most homogenous in-depth curing efficiency along with
      a low loss of mechanical resistance under cyclic fatigue. SIGNIFICANCE:
      Evaluation of flexural fatigue limit and curing efficiency correlate in terms of
      decreased mechanical strength due to insufficient light-curing intervals or light
      intensities. Initial promising fracture strengths do not correlate with a
      clinically more relevant fatigue loading and with the in-depth degree of
      conversion, both accounting for a significantly reduced strength performance.

PMID- 15978270
TI  - Shear bond strength and SEM evaluation of composite bonded to Er:YAG laser
      prepared dentin and enamel.
AB  - OBJECTIVES: The purpose of this study was to evaluate dentin and enamel bond
      strength to resin composite following high-speed rotary or Er:YAG laser
      preparation using a total etch adhesive system. The microstructure of resin-tooth
      interfaces was also investigated. METHODS: Human dentin and enamel specimens were
      prepared with a high-speed handpiece (KaVo) or Er:YAG laser (DELight) at
      manufacturer's recommended settings and etched with either 37% H(3)PO(4), laser
      etched, or not etched. Composite rods (Z-250, 3M/ESPE) were bonded to specimens
      with an adhesive (Adper Scotchbond Multi-Purpose, 3M/ESPE). After thermocycling,
      specimens were tested in shear to failure. RESULTS: Two-factor ANOVA detected
      significant differences in the main effects of preparation and etch type, and
      interaction (p<0.001). Post hoc analyses showed that in both dentin and enamel,
      only the acid-etched specimens had significantly higher mean bond strengths, with
      rotary-prepared specimens having significantly higher mean bond strengths versus
      laser prepared specimens. Within each preparation type, in both dentin and
      enamel, acid etch was better than laser etch, and laser etch was better than no
      etch. Scanning electron microscopy of laser-ablated specimens demonstrated
      significant surface scaling and subsurface fissuring beyond normal resin
      penetration depth. SIGNIFICANCE: Adhesion to laser-ablated or laser-etched dentin
      and enamel was inferior to that of conventional rotary preparation and acid
      etching.

PMID- 15978271
TI  - The influence of surface treatment and luting cement on in vitro behavior of two
      unit cantilever resin-bonded bridges.
AB  - OBJECTIVES: The purpose of this study was to find the optimal combination of
      surface pretreatment and luting cement for two-unit CoCr cantilever resin-bonded
      bridges. METHODS: Tensile peel, load and torque strength tests were performed
      using flat ground bovine teeth as substrate, four different commercially
      available luting cements, and CoCr beams as simulated cantilever resin-bonded
      bridges. The CoCr beams were pretreated with sandblasting or Rocatec. Tensile
      peel, load and torque strengths were determined 72h after cementation. The
      effects of sandblasting and Rocatec pretreatments on the morphology of the CoCr
      surface was investigated with SEM and EDAX analysis. RESULTS: The average
      strengths of the three tests showed that Rely X ARC, Resiment and Panavia were
      the same and significantly lower than UniFix. Rocatec showed a significantly
      higher average bond strength than sandblasting considering all tests. The peel
      test, which showed the lowest failure values, is clinically the most relevant
      test. This test showed that only UniFix as luting cement with sandblasting as
      pretreatment generates a significantly higher bond strength compared with the
      other cements and pretreatments. SIGNIFICANCE: Based on the results of this study
      the use of Unifix with sandblasting as metal surface pretreatment, is preferred
      for cementation of two-unit CoCr cantilever resin-bonded bridges.

PMID- 15978272
TI  - On-line analysis of CAL72 cells on two different titanium surfaces in a perfusion
      micro-bioreactor.
AB  - OBJECTIVES: The aim of the present experiment was to test a prototype
      microsensoric measuring system (micro-bioreactor) for the investigation of the
      biocompatibility of different titanium surfaces in a cell culture model. METHODS:
      Osteosarcoma cells of the cell line CAL72 were seeded onto titanium plates (10mm
      x 10mm x 1mm) and inserted into the culture chamber of the micro-bioreactor.
      Titanium plates with two different surface topographies (machined and titanium
      plasma-sprayed [TPS]) were used for this pilot investigation. Plastic plates
      served as controls. The online-sensoric device of the micro-bioreactor allowed
      the continuous monitoring of the metabolism of the cells and the control of the
      culture conditions. Over a period of 17 h changes in O(2)-consumption in the
      medium were measured by micro-electrodes and registered by the software of the
      system. The metabolic activity of the cells was calculated from the difference
      between the bypass and the chamber values. The cell proliferation and vitality
      were analyzed before and after the perfusion time in the micro-bioreactor. The
      cell morphology was studied using scanning electron microscopy. RESULTS: The
      cells on the machined surfaces showed the highest oxygen consumption after 15 h,
      after that it decreased. The cells on the TPS plates showed a lower oxygen
      consumption, which remained stable after 17 h. The highest oxygen consumption was
      seen with the cells on the control plastic plates. Concerning cell proliferation
      analysis, it could be shown that more vital CAL72 cells seeded onto TPS and
      plastic could be detected after the passage through the micro-bioreactor. Hence,
      the number of vital cells on the machined surface was reduced after the passage.
      SIGNIFICANCE: Within the limits of this experiment, the presented micro
      bioreactor system could offer a valuable method to examine the dynamic
      interactions of cells and materials under defined in vitro experimental
      conditions. While the presented system is already successfully used in the
      ecological/ecotoxicological field, its routine use for investigating dental
      materials on a cellular level has to be evaluated.

PMID- 15978273
TI  - Abrasive wear of resin composites as related to finishing and polishing
      procedures.
AB  - OBJECTIVES: Finishing and polishing procedures may cause topographical changes
      and introduce subsurface microcracks in dental composite restoratives. Since both
      of these effects may contribute toward the kinetics of wear, the purpose of this
      study was to assess and correlate the wear and surface roughness of minifilled
      and nanofilled composites finished and polished by different methods. METHODS:
      Specimens (n=10) made of a minifilled and a nanofilled composite were finished
      and polished with one of the four sequences: (1) tungsten carbide burs plus
      Al(2)O(3)-impregnated brush (CbBr) or (2) tungsten carbide burs plus diamond
      impregnated cup (CbCp), (3) diamond burs plus brush (DmBr) or (4) diamond burs
      plus cup (DmCp). As a control, abrasive papers were used. After surface roughness
      had been quantified, three-body abrasion was simulated using the OHSU wear
      machine. The wear facets were then scanned to measure wear depth and post-testing
      roughness. All sets of data were subjected to ANOVA and Tukey's tests
      (alpha=0.05). Pearson's correlation test was applied to check for the existence
      of a relationship between pre-testing roughness and wear. RESULTS: Significantly
      smoother surfaces were attained with the sequences CbBr and CbCp, whereas DmCp
      yielded the roughest surface. Regardless of the finishing/polishing technique,
      the nanofilled composite exhibited the lowest pre-testing roughness and wear.
      There was no correlation between the surface roughness achieved after
      finishing/polishing procedures and wear (p=0.3899). SIGNIFICANCE: Nano-sized
      materials may have improved abrasive wear resistance over minifilled composites.
      The absence of correlation between wear and surface roughness produced by
      different finishing/polishing methods suggests that the latter negligibly
      influences material loss due to three-body abrasion.

PMID- 15978274
TI  - The effects of thermal mismatch and fabrication procedures on the deflection of
      layered all-ceramic discs.
AB  - OBJECTIVES: Residual thermal stress caused by thermal incompatibility of ceramic
      core and veneering porcelain in all-ceramic restorations might induce fracture or
      distortion of the restoration. The aim of this study was to evaluate the thermal
      compatibility between a ceramic core and veneering porcelain by measuring the
      bending of layered discs and to compare the result with the thermal mismatch
      values. METHODS: Thirty-five heat-pressed ceramic core discs were made and
      divided into seven groups (n=5). One group of discs was used as control and
      subjected only to firing cycles, while the other groups of discs were veneered
      with porcelains. The mismatch of thermal contraction coefficient values of the
      Empress 2 Core and veneer porcelains used ranged from -3.7 to 3.8 ppm/ degrees C.
      RESULTS: The Empress 2 Core disc without a veneer (control) was not significantly
      deflected by the fabrication procedures. The deflection of layered discs was
      strongly influenced by the degree of thermal mismatch during fabrication
      procedures. The greatest deflection occurred during the 2nd dentin firing and
      with the largest mismatch either positive or negative. SIGNIFICANCE: The
      deflection test proved to be a reliable test method for the evaluation of thermal
      compatibility of porcelains in all-ceramic systems.

PMID- 15978275
TI  - Effect of coupling agents on the local mechanical properties of bioactive dental
      composites by the nano-indentation technique.
AB  - OBJECTIVES: To examine the use of nano-indentation as a method of determining the
      interfacial mechanics of bioactive composites for mandibular bone substitutes.
      METHODS: Three coupling agents (PMMA-MAA, PMMA-MA and silane) were used to treat
      hydroxyapatite (HA) particles before incorporation into a polymethylmethacrylate
      (PMMA) matrix. Nano-indentation was used to determine the hardness and Young's
      modulus on the HA particle surface, at the HA/PMMA interface and in the PMMA
      matrix region for each of the four groups. In addition bulk four-point bending
      tests were conducted on each of the four groups as a comparison. RESULTS: The
      findings resulted in significant differences in the local interfacial Young's
      modulus between the polymer-treated composites and the uncoupled control
      specimens with a marked improvement (50%) in modulus with either polymertreated
      group. Similarly, the bending modulus of the polymer-treated groups was
      significantly higher than the un-treated control group; however, these
      differences were not as pronounced (approximately 15%). SIGNIFICANCE: The co
      polymer-treated composites resulted in improved interfacial modulus as compared
      to the un-treated controls and that the nano-indentation technique is a powerful
      tool for understanding the local interfacial mechanics of bioactive composites.

PMID- 15978276
TI  - Color formulation and reproduction of opaque dental ceramic.
AB  - OBJECTIVES: The purpose of this study was to determine the validity and accuracy
      of mixing opaque feldspathic dental ceramic to obtain specific shades using two
      methods: (1) Concentration Additivity of Optical Parameters (CALAB) and (2)
      Concentration Additivity of Kubelka-Munk Optical Coefficients (CAK/S). METHODS: A
      total of 25 opaque feldspathic dental ceramic specimens were fabricated by mixing
      six different pure shades in different concentrations. The reflectance spectra
      were measured and the actual CIELAB L*, a* and b* coordinates were obtained for
      the 25 specimens. The CALAB and CAK/S methods were used to predict the L*, a* and
      b* values with reference to the concentrations of the pure shades. Correlation
      analysis was carried out between the actual and predicted L*, a* and b* values
      for both methods. The color differences (DeltaE*) between actual and predicted
      L*, a* and b* values were also calculated and analyzed using repeated measures
      ANOVA. RESULTS: Pearson's correlation coefficients between predicted and actual
      values for both methods were greater than 0.98. The mean DeltaE*s were 0.24
      (0.11) for CALAB method and 0.21 (0.11) for the CAK/S method. The repeated
      measures ANOVA revealed a statistically significant difference (P=0.0213) between
      the mean DeltaE*s from the two methods. SIGNIFICANCE: Both methods produced mean
      DeltaE*s between the actual and predicted methods that were below the threshold
      of human perceptibility. The simpler CALAB method can be used to determine the
      opaque ceramic mixture for specific shades with accuracy.

PMID- 15978277
TI  - Influence of annealing temperature on the strength of dental glass ceramic
      materials.
AB  - OBJECTIVES: Dental glass ceramic components are always loaded by residual
      stresses because of the manufacturing process. For a reliable mechanical
      characterization, residual stress-free specimens are needed. Residual stresses
      can be removed by an annealing process. The hypothesis of this work was, that the
      annealing temperature must be individually chosen to reliably remove possible
      residual stresses without changing the characteristics of the glass ceramic
      material. METHODS: Knoop-indented specimens made of the glass ceramic materials
      Duceram Opaker (Degudent, Hanau, Germany, formerly Ducera, Rosbach, FRG), Empress
      1 (Ivoclar Vivadent, Schaan, Liechtenstein), In-Ceram Alumina (Vita Zahnfabrik,
      Bad Sackingen, Germany), Optec OPC (Jeneric Pentron, Wellingford, USA), and Vita
      Omega Opaker (Vita Zahnfabrik, Bad Sackingen, Germany) were annealed at various
      temperatures below and above the respective glass transition temperature. The
      Weibull strength parameters and the lengths of the indentations before and after
      annealing were determined. RESULTS: A strength increase caused by relaxation of
      residual stresses was found after annealing at elevated temperatures. A local
      maximum of increased strength was determined after annealing at a temperature of
      100K below the glass transition temperature. After annealing at temperatures
      above the glass transition temperature, microplasticity was observed.
      SIGNIFICANCE: It is recommended to anneal glass ceramic components that are
      intended to be mechanically characterized at a temperature 100K below the
      respective glass transition temperature before testing to determine 'true'
      mechanical values that are not influenced by possible residual stresses.

PMID- 15978278
TI  - Comparison of CIELAB DeltaE(*) and CIEDE2000 color-differences after
      polymerization and thermocycling of resin composites.
AB  - OBJECTIVES: Though instrumental technologies have been widely used for
      quantifying color of esthetic dental materials, the sizes for the perceptible or
      acceptable color-difference varied. Instead of the CIELAB
      DeltaE(*)(DeltaE(ab)(*)) formula, the CIEDE2000 (DeltaE(00)) formula that
      included weighting and parametric functions was introduced. The objective of this
      study was to determine the correlation between color-difference values of
      DeltaE(ab)(*) and DeltaE(00) after polymerization and thermocycling of dental
      resin composites. METHODS: Color-differences were calculated between
      unpolymerized and polymerized, and between polymerized and thermocycled resin
      composites. Color was measured relative to the standard illuminant D65 over a
      white background with SCE geometry. Regression analyses were performed between
      the color difference values of DeltaE(ab)(*) and DeltaE(00). RESULTS: There were
      significant correlations between DeltaE(ab)(*) values and DeltaE(00) values after
      polymerization and thermocycling (p<0.01), and the correlation coefficient was
      0.99 and 0.98, respectively. SIGNIFICANCE: Within the limit of this study, the
      results suggest that two color-difference formulas can be used interchangeably
      for the evaluation of the color-difference of resin composites after
      polymerization and thermocycling. However, for the evaluation of changes in
      separate color parameters such as lightness, chroma and hue, the DeltaE(00)
      formula could be considered for the color evaluation of esthetic dental materials
      after confirming with human observer responses.

PMID- 15978279
TI  - Blue light generates reactive oxygen species (ROS) differentially in tumor vs.
      normal epithelial cells.
AB  - OBJECTIVES: Blue light of high intensity is commonly used in dentistry to
      activate polymerization of resin restorative materials. Other than its effects on
      the retina, the biological effects of blue light (380-500nm wavelengths) are
      poorly studied. Limited evidence suggests that blue light acts by forming
      intracellular reactive oxygen species (ROS) that then affect critical cell
      functions. If the biological effects of blue light are redox-mediated,
      antioxidants might be used to mitigate unwanted side effects of blue light during
      clinical use, or blue light might be used therapeutically to modulate redox
      sensitive cell signaling responses. METHODS: Intracellular ROS were estimated
      using HFLUOR-DA (dihydrofluorescein diacetate), a vital fluorescein-based, redox
      sensitive dye. ROS were measured in normal (NHEK) and oral squamous carcinoma
      (OSC2) epithelial cells, shown previously to respond differentially to blue light
      irradiation. Two-hour cumulative levels of ROS and approximate ROS lifetimes were
      measured after irradiation doses of 5-30 J/cm(2). The blue light-induced
      generation of ROS was further tested by the ability of the antioxidants N
      acetylcysteine (NAC) and vitamin E to mitigate intracellular ROS levels. RESULTS:
      Dose-dependent ROS levels were generated in both NHEK and OSC2 cells, but
      cumulative levels were higher and persisted longer in the OSC2 cells. Both
      vitamin E and NAC significantly reduced blue-light-induced levels of ROS, but
      were more effective in the OSC2 cells. SIGNIFICANCE: The induction of
      intracellular ROS by blue light implies that redox effects may mediate cellular
      responses to blue light. This result suggests the opportunity to mitigate any
      effects of direct or coincident exposure during dental treatment via
      antioxidants, and the opportunity to exploit differences in redox processing
      among cells for possible treatment of epithelial cancer or wound healing.

PMID- 15978280
TI  - The two Cg-timp mRNAs expressed in oyster hemocytes are generated by two gene
      families and differentially expressed during ontogenesis.
AB  - We previously characterized a Crassostrea gigas tissue inhibitor of
      metalloproteinase (Cg-timp 1.3) with potential role in wound healing and defense
      mechanisms. Here we isolated a second cDNA (Cg-timp 1.1) encoding a protein that
      contains the characteristic signature of TIMP proteins. Sequence analysis of the
      two transcripts showed that they originate from two distinct genes. The two
      proteins, Cg-TIMP 1.1 and 1.3, are closely related and share 81% identity.
      Northern blot analysis of Cg-timp gene expression in adult oyster hemocytes
      indicated that the ratio between the two transcripts was constant from one oyster
      to another (Cg-timp 1.1 and 1.3 represent 32 and 68%, respectively). Conversely,
      during ontogenesis the expression pattern of the two Cg-timp genes was different.
      Indeed, Cg-timp 1.3 mRNAs were detected from the larval D stage whereas Cg-timp
      1.1 transcripts were undetectable up to 22 days post-fertilization. The
      difference in expression pattern of the two Cg-timp genes may reveal distinct
      implications of these genes in the embryos and larvae developments.

PMID- 15978282
TI  - Cloning, expression and phylogenetic analysis of Hemolin, from the Chinese oak
      silkmoth, Antheraea pernyi.
AB  - The Chinese oak silk moth Antheraea pernyi is an important silk producer. To
      understand microbial resistance of this moth, we cloned Hemolin, encoding a
      multifunctional immune protein belonging to the immunoglobulin superfamily, and
      examined the expression in gonads and fat body. The ApHemolin amino acid sequence
      was compared to other Hemolin sequences in order to predict functional sites.
      Several sites were conserved; among them a phosphate binding site, which
      according to 3D structure modelling does not appear in neuroglian, the
      phylogenetically closest related protein. In addition, two conserved KDG
      sequences in the C-C' loop of immunoglobulin domains 1 and 3, give rise to gamma
      turns, which is a common motif in the C'-C'' loop of the hypervariable region L2
      in vertebrate immunoglobulins. The comparisons also show variable regions of
      specific interest for future studies of hemolin and its interaction with
      microbial entities.

PMID- 15978281
TI  - Recombinant expression and anti-microbial activity of anti-lipopolysaccharide
      factor (ALF) from the black tiger shrimp Penaeus monodon.
AB  - Anti-lipopolysaccharide factors (ALFs), originally characterized from horseshoe
      crabs, have been recently identified from hemocytes of the black tiger shrimp,
      Penaeus monodon, by a genomic approach. In order to characterize the properties
      and biological activities of this immune effector in shrimp, ALFPm3, the most
      abundant isoform found in P. monodon, was expressed in the yeast Pichia pastoris.
      Large-scale production in fermentor provided 262 mg/l of recombinant ALFPm3 which
      was purified to homogeneity by single chromatography step on expanded-bed
      Streamline SP6XL. The rALFPm3 was further characterized in terms of N-terminal
      sequencing and mass spectrometry. Anti-microbial assays demonstrated that rALFPm3
      has a broad spectrum of anti-fungal properties against filamentous fungi, and
      anti-bacterial activities against both Gram-positive and Gram-negative bacteria,
      associated with a bactericidal effect. Interestingly, rALFPm3 is highly efficient
      against various Vibrio species including strains pathogenic for shrimp. Finally,
      a synthetic peptide corresponding to a part of the putative LPS-binding site of
      ALFPm3 was shown to display activities mainly directed against Gram-positive
      bacteria indicating the involvement of the full molecule to the anti-microbial
      activity for Gram-negative bacteria.

PMID- 15978283
TI  - A novel soluble form of the CSF-1 receptor inhibits proliferation of self
      renewing macrophages of goldfish (Carassius auratus L.).
AB  - Macrophage colony-stimulating factor (CSF-1) is the principal regulator of the
      survival, proliferation, and differentiation of macrophages and their precursors.
      CSF-1 activity is tightly controlled through mechanisms regulating gene
      expression of CSF-1 and its membrane-bound receptor (CSF-1R), as well as by
      receptor-mediated endocytosis, metabolic processing, and inhibition of downstream
      signaling. Herein we describe a novel mechanism for control of CSF-1 activity.
      Spontaneously growing goldfish (Carassius auratus L.) macrophages actively
      produced a soluble form of CSF-1R (sCSF-1R) that appears to compete for ligand
      binding with membrane CSF-1R. The sCSF-1R transcript encodes only for the ligand
      binding portion of the receptor, but is derived from a full-length mRNA species
      as determined by sequence analysis. Gene expression was associated with decreased
      proliferation and differentiation of primary macrophages, decreased growth factor
      activity in culture supernatants, and marked phenotypic changes that culminated
      in apoptotic cell death. Recombinant sCSF-1R inhibited macrophage proliferation
      at nanomolar concentrations. Antibodies against recombinant sCSF-1R identified
      native sCSF-1R in primary macrophage culture supernatants and fish serum, and
      suggested the presence of endogenous mechanisms temporally regulating sCSF-1R
      release. This is the first report of a soluble CSF-1R and points to intrinsic
      mechanisms of hematopoietic control that may be conserved across evolution in
      discrete self-renewing macrophage populations.

PMID- 15978284
TI  - Immunogenicity of a bovine viral diarrhea virus E2-C3d fusion protein containing
      a bovine homolog of C3d.
AB  - Recently we demonstrated that attachment of three copies of murine C3d (muC3d) to
      the E2 envelope protein of bovine viral diarrhea virus results in a 10,000-fold
      increase in the immunogenicity of E2. Here we describe the cloning of the bovine
      homolog of C3d (boC3d), construction of an E2-boC3d expression cassette and
      expression and purification of the E2-boC3d fusion protein. We then show that E2,
      when coupled to boC3d, exhibits greatly enhanced immunogenicity. Thus, boC3d
      represents the second mammalian C3d homolog, thus far, shown to enhance the
      immunogenicity of a protein to which it has been coupled. Although the primary
      sequence of boC3d differs from muC3d by about 19%, we were able to demonstrate
      the enhanced immunogenicity of E2-boC3d using mice. The ability of boC3d to
      function in mice provides a less costly and more convenient animal model than
      cattle for the preliminary evaluation of E2-boC3d and other bovine antigen-boC3d
      fusion proteins.

PMID- 15978285
TI  - Development of a chronic zinc biotic ligand model for Daphnia magna.
AB  - The individual effects of the cations Ca(2+), Mg(2+), Na(+), and H(+) on the
      chronic toxicity of Zn to the waterflea Daphnia magna were investigated in
      different series of univariate experiments, resulting in the development of a
      chronic Zn biotic ligand model (BLM) for this species. Using the mathematical
      approach based on a linear relationship between cation activity and metal
      activity at the EC(x) level, the following stability constants for binding of
      competing cations to the biotic ligand (BL) were derived: logK(CaBL) = 3.22,
      logK(MgBL) = 2.69, logK(NaBL) = 1.90, and logK(HBL) = 5.77. With the derived
      constants and a logK(ZnBL) of 5.31, two different BLMs that predict chronic zinc
      toxicity (EC(50), no observed effect concentration (NOEC)) for D. magna as a
      function of water characteristics were developed. Fractions of binding sites
      occupied by Zn at the considered effect levels EC(50) and NOEC were 0.127 and
      0.084, respectively. The NOEC-based model predicts the Zn toxicity within a
      factor of 2, while the chronic EC(50) could be predicted within a factor of 1.5.
      In the future, these chronic Zn BLMs for D. magna can improve the ecological
      relevancy of zinc risk assessments by decreasing the bioavailability-related
      uncertainty of zinc toxicity.

PMID- 15978286
TI  - Toxicity and hazard assessment of fipronil to Daphnia pulex.
AB  - Hazard assessments based on two measures of toxicity were conducted for the water
      flea, Daphnia pulex (Leydig) exposed to the insecticide, fipronil. The measures
      of toxicity obtained were 48 h acute lethal concentration estimates, and a direct
      measure of population growth rate, the 10-day instantaneous rate of increase
      (r(i)). Additionally, life tables were developed after exposure to several
      concentrations to tease out the apparent sublethal effects of this insecticide to
      D. pulex. The acute LC(50) was estimated to be 0.0156 (0.0088-0.083) mg/L. In the
      10-day population growth rate study, extinction of D. pulex populations occurred
      after exposure to 0.08 mg/L of fipronil, which was equivalent to the 48 h acute
      LC(75). The NOEC and LOEC for population size after a 10-day exposure to fipronil
      were 0.03 and 0.05 mg/L, respectively. An expected environmental concentration
      (EEC) in freshwater lakes/ponds based on an application rate of 250 mg ai/ha
      (recommended rate for use in Tephritid fruit fly control programs) was estimated
      to be 0.00017 mg/L. Hazard assessments were developed by dividing the EEC by the
      LC(50) and NOEC for population size. The assessments based on the LC(50) and NOEC
      for population size were 0.011 and 0.0057, respectively, indicating that fipronil
      does not pose a hazard to D. pulex when applied at the rates recommended for
      control of Tephritid fruit flies. Life tables were developed after exposure to
      two insecticide concentrations and a control. Exposure to 0.015 mg/L, the
      approximate 48 h acute LC(50), resulted in only a slight decrease in the net
      reproductive rate (R(o)), birth rate (b), and intrinsic rate of increase (r(m))
      and an increase in generation time (T), death rate (d), and doubling time (DT)
      compared to the control. Exposure to 0.03 mg/L, the approximate 48 h acute
      LC(60), and NOEC in the 10-day study, resulted in a 57% decline in the net
      reproductive rate, a 1.45-fold decrease in birth rate, a 1.5-fold decrease in the
      intrinsic rate of increase, a 6-day increase in generation time, a 4-fold
      increase in death rate, and a 1.5-fold increase in doubling time. The stable age
      distribution (after 60 days) of D. pulex changed after exposure to fipronil.
      Increasing concentrations of fipronil resulted in a decrease in the percentage of
      individuals in the first, second, third, and fourth juvenile stages, an increase
      in the adult stage, and no change in the adolescent stage. These results indicate
      that certain concentrations of fipronil approaching the LC(50) can negatively
      affect population parameters of D. pulex, but that EECs, at least for fruit fly
      control, should be lower than the concentration necessary to cause damage.

PMID- 15978287
TI  - Modeling the concentration-response function of the herbicide dinoseb on Daphnia
      magna (survival time, reproduction) and Pseudokirchneriella subcapitata (growth
      rate).
AB  - Models describing dose-response relationships are becoming increasingly popular
      in ecotoxicology. They allow simple and thorough evaluations of toxicity test
      results, including inter- and extrapolations to concentrations or exposure times
      other than those tested. Simple parametric regression models are of particular
      interest because their parameters may be attributed mechanistic meanings and they
      can be applied without sophisticated mathematical and computational support. We
      recently proposed a four-parameter logistic regression model to fit the survival
      data of Daphnia magna under dinoseb stress. The model parameters are the maximum
      survival time, the minimum time required for an individual to die, effect
      concentration, EC(50), and a curve shape parameter. This model has now been
      applied to compare the lethality and reproduction toxicity of D. magna and the
      growth inhibition of Pseudokirchneriella subcapitata under dinoseb stress. It can
      be fitted adequately to all the measured data and the parameters can be
      attributed biological meanings in any of the three endpoints. A comparison of the
      modeled concentration-response functions of all three endpoints for dinoseb
      toxicity shows that the range of ECs with respect to both D. magna and algae is
      steep (a decrease of between 0.1 and 0.6 mg/L). The survival and reproduction of
      D. magna exhibit similar characteristic concentration-response functions and
      toxicities. The statistical no-effect concentration (SNEC) is 0.14 (survival) and
      0.11 (reproduction)mg/L, respectively. On the other hand, algae seem to be less
      sensitive to dinoseb than D. magna (SNEC: 0.48 mg/L). However, further
      investigations of individual algae may lead to a more suitable comparison. We
      speculate that the four parameters of the model function can be related to
      specific properties of chemicals and organisms. Characterization of these
      properties would allow simple and appropriate estimation of the toxic effects of
      these chemicals.

PMID- 15978288
TI  - Bioavailability of phthalate congeners to earthworms (Eisenia fetida) in
      artificially contaminated soils.
AB  - Bioavailability of phthalate congeners, dimethyl phthalate, diethyl phthalate, di
      n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and dioctyl
      phthalate, to earthworms (Eisenia fetida) were studied when earthworms were
      exposed to two artificially contaminated agricultural and forest soils. Only DBP
      and DEHP were detected in earthworms. The uptake kinetics of DBP and DEHP in
      earthworms was fast within the initial 10 days followed by a nearly steady state
      for the subsequent 20 days. An equilibrium partitioning model could be used to
      describe the uptake kinetics of DBP and DEHP by earthworm in two types of soils
      (r = 0.709-0.864). The average biota-to-soil accumulation factors (BSAFs) of DBP
      and DEHP at 5 mg kg(-1) in soil were 0.27 +/- 0.07 and 0.17 +/- 0.03,
      respectively, in agricultural soil, while the BSAFs were 0.21 +/- 0.06 and 0.07
      +/- 0.02, respectively, in forest soil. The concentrations of phthalates in
      earthworms increased with increasing concentrations of phthalates in soil. There
      was a significant correlation between logC(soil) and logC(worm), with r = 0.999
      0.993, demonstrating a single linear partitioning of phthalates between soil and
      earthworms. The bioavailability of DBP and DEHP was assessed by Soxhlet,
      methanol, and methanol-water (1:1) extraction methods. Our results indicated that
      the extractable amounts of freshly added DBP and DEHP in soils by these
      extraction methods were significantly correlated with those in earthworms. It was
      observed that the extractable DBP and DEHP by the methanol and methanol-water
      (1:1) extraction methods decreased with their increasing residence time in soil.
      In contrast, the amount extracted by the Soxhlet extraction method did not show a
      similar decline. Therefore, Soxhlet extraction was a poor indicator of the
      bioavailability of DBP and DEHP to earthworms in soil, which could lead to
      overestimation of the risk of soil-associated DBP and DEHP. The extractable DBP
      and DEHP by methanol and methanol-water (1:1) significantly decreased over 440
      days. Compared with the methanol-water (1:1) extraction method, the methanol
      extraction method was preferred for its ability to predict the bioavailability of
      DBP and DEHP in aged soils.

PMID- 15978289
TI  - Avoidance of Cu- and Zn-contaminated soil by three ecologically different
      earthworm species.
AB  - Earthworm avoidance response to soils contaminated with harmful substances has
      been proposed as a potential tool for assessing soil toxicity with low test
      effort. In the present study, the objective was to find out whether three
      ecologically different earthworm species, Aporrectodea tuberculata (Eisen),
      Lumbricus rubellus (Hoffmeister), and Dendrobaena octaedra (Savigny), avoid soils
      simultaneously spiked with Cu and Zn. In addition, metal-contaminated field soil
      taken close to a Cu-Ni smelter was tested with A. tuberculata using a two-section
      avoidance lest procedure. All three earthworm species clearly avoided Cu/Zn
      contaminated soil but differently: D. octaedra was the most sensitive species,
      responding to low metal concentrations, whereas L. rubellus responded only to the
      highest metal concentration tested, being the least sensitive species. Moreover,
      A. tuberculata showed clear avoidance response to the metal contaminated field
      soil. In conclusion, the results indicate that earthworm avoidance behavior is an
      ecologically relevant parameter for assessing harmfulness of metal contaminated
      soils, both spiked and field-contaminated soils. However, it is important to
      consider the specific species to be used in the earthworm avoidance test
      procedure.

PMID- 15978290
TI  - Using the nucleolar biomarker and the micronucleus test on in vivo fish fin
      cells.
AB  - This study was aimed at developing the nucleolar biomarker and the micronucleus
      test on in vivo fish fin cells for assessing water cytotoxicity and genotoxicity.
      Both biomarkers can be used either jointly or separately on fins of the same fish
      during the experiment. For studying the nucleolar characteristics, small pieces
      of the fin edge were cut several times during 30-180 min of fish exposure. For
      micronucleus testing, the fin tissue regenerating after its cutting was
      investigated after 2-5 days of fish incubation. Effects of copper (0.1 and 2.5
      mg/L), cadmium (0.005 and 1.0 mg/L) ions and chloral hydrate (400 and 800 mg/L)
      solutions were studied on cells of common carp (Cyprinus carpio L.), crucian carp
      (Carassius auratus gibelio Bloch.), and Mozambique tilapia (Tilapia (Sautherodon)
      mossambica) using a set of nucleolar characteristics (the number of nucleoli per
      cell, the size of a single nucleolus, and the percentage of cells with
      heteromorphic paired nucleoli) and the frequencies of cells with micronuclei and
      double nuclei. Substantial changes in parameters of nucleolar activity of fin
      cells were found to be caused by cadmium and copper impact. In comparison to
      blood cells, gill and fin cells were more sensitive as demonstrated by their
      nuclear damages after the chloral hydrate influence. Fin cells were useful to
      determine periodically cytotoxic and genotoxic effects of organic and inorganic
      substances in the same individual fish without any disruption of its
      physiological functions.

PMID- 15978291
TI  - Interannual variability in fish biomarkers in a contaminated temperate urban
      estuary.
AB  - During the past decade the Swan-Canning estuary, Western Australia, has shown
      signs of stress which has been attributed to high nutrient inputs. There is
      little information on the effect of nonnutrient contaminants on biota inhabiting
      the estuary. A suite of biomarkers was measured on black bream (Acanthopagrus
      butcheri) to determine whether annual variations in fish biomarkers exist in the
      wet (winter) and dry (summer) seasons. Serum sorbitol dehydrogenase showed no
      significant differences between years, indicating that measured mixed-function
      oxygenase (MFO) enzyme activities were not affected by annual variations in
      hepatic tissue damage. Ethoxyresorufin-O-deethylase activity was lower in female
      black bream than in male fish while ethoxycoumarin-O-deethylase activity was not
      influenced by gender. Biomarker levels measured at various sites confirm that
      major roads and drains are significant contributors of MFO-inducing chemicals
      into the Swan-Canning estuary. No consistent upstream or downstream gradient in
      biomarker response was identified. The ratio of naphthalene-type to
      benzo(a)pyrene-type biliary metabolites was linked to runoff from urban areas
      into the estuary. There was high annual variability in all biomarkers in both
      seasons, suggesting that biannual monitoring is required to evaluate the effect
      of contaminants on the biota in the estuary.

PMID- 15978292
TI  - Evaluation of sublethal biomarkers in Litopenaeus vannamei on foodborne exposure
      to methyl parathion.
AB  - Sublethal effects of foodborne exposure to methyl parathion (0.62 and 1.31 microg
      methyl parathion*g(-1) dry weight of food) on juveniles of Litopenaeus vannamei
      using integrated biochemical (acetylcholinesterase (AChE) and ATPases) and
      physiological (feeding rate (FR), egestion rate (ER), and hepatosomatic index
      (HI)) biomarkers were evaluated. The HI was significantly higher in controls than
      in pesticide treatments. The FR was significantly lower in controls than in
      pesticide treatments while no significant differences were detected in the ER.
      AChE activity was significantly higher in controls than in pesticide treatments
      (control = 0.11 +/- 0.02; solvent control = 0.11 +/- 0.03; 0.62 = 0.07 +/- 0.01;
      1.31 = 0.08 +/- 0.02 microM*min(-1)*mgprotein(-1)). The total-ATPase activity was
      significantly lower in controls than in pesticide treatments (control=77.90+/
      12.41; solvent control = 83.69 +/- 22.05; 0.62 = 110.03 +/- 22.17; 1.31 = 121.54
      +/- 19.84 microM P(i)*h(-1)*mgprotein(-1)). The Mg(2+)-ATPase activity was
      significantly higher in treatments than in controls (control = 65.14+/-10.76;
      solvent control = 75.12 +/- 21.10; 0.62 = 100.53 +/- 20.97; 1.31 = 108.94 +/-
      17.26 microM P(i)*h(-1)*mgprotein(-1)). Finally, the results obtained for the
      Na(+)/K(+)-ATPase activity were significantly higher in control and in 1.31 than
      in solvent control and in 0.62 (control = 14.06+/-2.63; solvent control=7.30 +/-
      4.13; 0.62 = 7.60 +/- 3.81; 1.31 = 13.42 +/- 2.88 microM P(i)*h(-1)*mgprotein(
      1)). The results in this study showed that pulse exposures to methyl parathion
      via food could elicit measurable effects on the marine shrimp L. vannamei,
      indicating that foodborne exposure can be a reliable toxicological procedure and,
      if combined with pulse exposures, could also simulate more realistic exposure
      scenarios.

PMID- 15978293
TI  - Comprehensive assessment of aquatic community responses to a new anionic
      surfactant, high-solubility alkyl sulfate.
AB  - High-solubility alkyl sulfate (HSAS) is a new anionic surfactant for use in
      consumer product applications that provides enhanced water solubility and
      improved water hardness tolerance. A comprehensive model stream ecosystem
      investigation was conducted to assess ecological and toxicological effects of
      HSAS on stream invertebrates. Model streams were dosed with HSAS for a period of
      56 days following 56 days of colonization in a single-pass, flow-through system.
      Exposures were control and 9.1, 24.1, 64.0, 165.8, and 426.5 microg/L based on
      specific analytical detection methods. Benthic abundance on gravel substrates,
      drift, and insect emergence were assessed. Several taxonomically unrelated taxa
      were found sensitive to HSAS and formed the basis of toxicological conclusions.
      Abundance or biomass of a limpet (Ferrissea), a bivalve (Corbicula), flatworms
      (Turbellaria), and a mayfly (Stenonema) was reduced at concentrations ranging
      from 165.8 to 426.5 microg/L. Principal response curve analysis, a constrained
      form of principal components analysis, demonstrated consistency with univariate
      analyses and identified similar populations as being sensitive to HSAS.
      Comparison with historical studies from the same testing site, streams, and
      experimental design, but with structurally related alkyl sulfate and alkyl
      ethoxysulfate anionic surfactants, revealed several similar trends in response
      profiles at the population level for both tolerant and sensitive species. Based
      on the comprehensive nature of the study, strength of data trends, and
      demonstrated sensitivity of the aquatic communities contained in the experimental
      system, the no-observed-effect concentration for HSAS was concluded to be 64.0
      microg/L. An application factor of 1 is justified for deriving a predicted no
      effect concentration) for HSAS in aquatic systems.

PMID- 15978294
TI  - Toxicity of chromium(III) and chromium(VI) to the earthworm Eisenia fetida.
AB  - The effects of Cr(III) and Cr(VI) on the survival, behavior, and morphology of
      the earthworm, Eisenia fetida, in water at pH 6, 7, and 8 and their toxicity in
      10 different soils and an organic substrate have been assessed. A decrease in the
      pH of water resulted in increased toxicity of Cr to the earthworm. In water, both
      Cr species produced behavioral changes and morphological symptoms. The 48-h
      LC(50) values of Cr(III) at pH 6, 7, and 8 were 1.93, 2.55, and 2.78 mg/L, and
      those of Cr(VI) were 0.47, 0.61, and 0.63 mg/L, respectively. The 14-day median
      lethal concentrations (LC(50)) of Cr(III) and Cr(VI) for earthworm range from
      1656 to 1902 mg/kg for Cr(III) and from 222 to 257 mg/kg for Cr(VI) in soil. In
      the organic substrate, the LC(50) values of Cr(III) and Cr(VI) were 1635 and 219
      mg/kg, respectively. Stepwise multiple regression analysis predicted that clay
      content of soils accounted for 92% and 88% of the variation in the LC(50) values
      of Cr(III) and Cr(VI), respectively.

PMID- 15978295
TI  - The implications of copper fungicide usage in vineyards for earthworm activity
      and resulting sustainable soil quality.
AB  - To investigate the impact of copper-containing fungicides (copper oxychloride) on
      earthworms in South African vineyards, field inventories of earthworms in and
      between vine rows were carried out and compared to directly adjacent grassland.
      Also copper content, pH, organic matter content, and soil porosity were
      determined in these soils. This was combined with laboratory experiments to study
      the impact of vineyard soil characteristics on the burrowing and dispersal
      behavior of earthworms. Moreover, the direct toxic action of copper oxychloride
      on different endpoints of the earthworms (survival and growth) was studied.
      Copper oxychloride had a negative impact on these endpoints (decreased growth and
      survival related to increased copper body content) as well as on the behavioral
      aspect (decreased burrowing rate and avoidance of copper-containing soil).
      Moreover, there was an inverse relation between burrowing activity and soil bulk
      density that could also be related to the copper content. This may lead to a
      decrease in sustainable soil quality in vineyards.

PMID- 15978296
TI  - Fertility and content of cadmium in pheasant (Phasianus colchicus) following
      cadmium intake in drinking water.
AB  - In this study, the effects of cadmium applied per os on fertility, live weight of
      newly hatched chicks, and cadmium concentrations in some organs of young and
      adult pheasants were investigated. The metal was applied at the concentration of
      1.5 mg Cd(2+)/L during 3 months. After the egg laying, the numbers of eggs laid,
      cracked, and unfertilized were determined and the live weights of newly hatched
      chicks were measured. The cadmium concentrations in liver, kidney, and muscle (m.
      pectoralis) of young and adult pheasants were analyzed. We found that cadmium
      exposure of the adults did not affect the number of eggs laid but resulted in
      more eggs being damaged. Hatchlings were significantly heavier in the cadmium
      treated group (21.36 +/- 2.28 g) compared to the control group (20.91 +/- 1.97 g)
      4 weeks after the cadmium intake. Higher cadmium concentrations were observed in
      the muscle and kidney tissue of newly hatched pheasants after 4 weeks compared to
      the cadmium-exposed groups after 8 and 12 weeks. The cadmium concentrations in
      kidneys and liver increased significantly in adult pheasants. The metal had
      accumulated especially in kidneys of the adult pheasants and reached levels up to
      9.64 mg/kg wet weight 3 months after the daily cadmium intake in drinking water.
      The concentration in liver of the adults was 3.53 mg/kg wet weight.

PMID- 15978297
TI  - Accumulation of metals and its effects in Brassica juncea (L.) Czern. (cv.
      Rohini) grown on various amendments of tannery waste.
AB  - The metal accumulation potential and its tolerance in the plants of Brassica
      juncea (L.) Czern. (cv. Rohini) grown on various amendments of tannery sludge
      (10%, 25%, 35%, 50%, 75%, 100%) were studied after 30, 60, and 90 days after
      sowing. These plants were found to be effective accumulators of metals (Cr, Fe,
      Zn, and Mn); however, the seeds accumulated the least quantities of all the
      metals tested. The oil content of the seeds was found to increase up to 35%
      tannery sludge followed by a decrease. An increase in the photosynthetic
      pigments, protein, and sugar contents was recorded at the lower amendments of
      tannery sludge at initial exposure periods followed by a decrease compared to
      their respective controls. However, the malondialdehyde, proline, and ascorbic
      acid contents of the roots and leaves of the plant increased at all the sludge
      amendments and exposure periods, compared to their respective controls. The
      levels of cysteine and nonprotein thiol contents in the roots and leaves of the
      treated plant were found higher at all the sludge amendments and exposure periods
      except at 90 days, where a decrease was observed in the leaves at 100% tannery
      sludge as compared to their respective controls. The tolerance exhibited by the
      sludge-grown plants of B. juncea in the present study may be attributed to the
      enhanced level of the antioxidants induced under stress conditions.

PMID- 15978298
TI  - Acute toxicity of Euphorbia kamerunica on Oreochromis niloticus.
AB  - A series of static short-term bioassays was conducted to assess the acute
      toxicity of the plant Euphorbia kamerunica on the fingerlings of Oreochromis
      niloticus. The 96-h LC(50) was computed using two methods: probit analysis and
      the arithmetic graphic method. The overall mean value of 0.023 +/- 0.002 g/L was
      obtained. Aquatic invertebrates are generally much more sensitive than fish
      species. Poisoning of streams with this plant to capture fish may therefore have
      ecological consequences, as nontarget aquatic animals may be killed in the
      process. Water quality standards for the protection of aquatic life are based on
      toxicity data for the most sensitive species found in the aquatic environment. We
      therefore suggest that E. kamerunica should not be used directly in freshwater
      bodies without detailed studies of its long-term effects on nontarget organisms
      as well its structure-activity relationship.

PMID- 15978299
TI  - Risk assessment through dietary intake of total diet contaminated with pesticide
      residues in Punjab, India, 1999-2002.
AB  - Forty-six samples each of vegetarian and nonvegetarian total diet consumed from
      March 1999 to December 2002 by male subjects in the age group of 19-24 years were
      analyzed to assess their risk through dietary intake with respect to pesticide
      residues. The results revealed low dietary intake of levels of Sigma
      dichlorodiphenyltrichloroethane (DDT) and which were almost comparable to levels
      reported in developed countries. The results are indicative of contamination of
      total diet with pesticide residues despite a ban on the use of DDT and restricted
      use of lindane in agriculture only. Predominance of lindane residues indicates
      that liquid milk was a main contributory source as it comprises almost 21% to the
      total diet consumed per day. Concerted efforts by regulatory authorities and
      emphasis on judicious use of agrochemicals in pest control are required to
      decrease the burden of these chemicals in food stuffs to levels safe for dietary
      intake.

PMID- 15978300
TI  - Copper-induced changes in tissue enzyme activity in a freshwater mussel.
AB  - Changes in enzyme activity levels are of great diagnostic value. Lysosomal
      membrane is often the target of injury by xenobiotics, resulting in
      destabilization. Variations in the activity of acid phosphatase (ACP) a marker
      enzyme, in gills and hepatopancreas of the freshwater mussel Lamellidens
      corrianus (Lea) exposed to different concentrations of copper for 24, 120, and
      168 h are discussed. The aim was to determine if the metal caused any variation
      in enzyme activity in the two tissues studied and, if so, whether the length of
      exposure had any influence on enzyme activity. ACP activity was determined as
      described in Sigma Technical Bulletin No. 104 and expressed as micromoles of p
      nitrophenol liberated per milligram of protein per hour. Both concentration of
      the metal and length of exposure were found to influence enzyme activity. Higher
      concentrations of metals are assumed to induce stress proteins like
      metallothioneins.

PMID- 15978301
TI  - Trospium chloride for the treatment of overactive bladder with urge incontinence.
AB  - BACKGROUND: Urinary incontinence is caused by an overactive bladder, leading to
      symptoms of urgency, frequency, and incontinence. Urge incontinence occurs
      predominantly in women as they age. OBJECTIVES: This article reviews the current
      primary literature concerning the efficacy and tolerability of the
      anticholinergic agent trospium chloride (TCl) in the treatment of overactive
      bladder with symptoms of urge incontinence, urgency, and frequency. The
      pharmacokinetics of TCl are also reviewed. METHODS: Pertinent articles in English
      were identified through a search of MEDLINE (1966-present), EMBASE Drugs &
      Pharmacology (1980-third quarter 2004), Current Contents/Clinical Medicine (week
      42, 2003-week 41, 2004), Cochrane Database of Systematic Reviews, MICROMEDEX
      Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The
      search terms were overactive bladder, urinary incontinence, trospium, randomized
      controlled clinical trial, oxybutynin, tolterodine, scopolamine, imipramine,
      desipramine, and propantheline. RESULTS: TCl, a quaternary amine, exhibits high
      solubility in water but low oral bioavailability (9.6%) and poor central nervous
      system penetration. Approximately 80% of the absorbed fraction is renally
      eliminated as unchanged drug via active tubular secretion, with approximately 15%
      hepatically metabolized into a spiroalcohol and hydrolysis/oxidation products. In
      3 placebo-controlled studies, patients who received TCl had an increase in
      maximum bladder filling capacity and bladder compliance, with a reduction in
      maximum cystometric capacity (P < 0.005); however, only 1 of these studies showed
      an increase in bladder compliance, with reductions in maximum detrusor pressure
      (P < 0.001), number of voids/d (P < or = 0.001), and incontinence episodes/d (P <
      or = 0.001). In another placebo-controlled study, TCl reduced the number of
      voids/d and incontinence episodes/d (both, P < or = 0.001). In 2 double-blind
      studies, TCl and oxybutynin were similarly effective in significantly increasing
      maximum cystometric capacity and bladder compliance, and in significantly
      reducing maximum detrusor pressure compared with baseline (all, P < 0.001); there
      were no significant differences between the 2 treatments at end point. In a third
      double-blind study comparing TCl and tolterodine with placebo, only TCl
      significantly reduced the frequency of micturitions/d (P = 0.01). Commonly
      reported adverse effects in patients receiving TCl included dry mouth,
      constipation, and headache. CONCLUSIONS: In the 7 studies reviewed, TCl was
      effective and well tolerated in patients with urge incontinence caused by
      idiopathic detrusor muscle overactivity or neurogenic detrusor overactivity
      resulting from spinal cord injury. However, this agent was associated with
      anticholinergic adverse effects similar to those of other anticholinergic agents;
      careful monitoring of tolerability is required.

PMID- 15978302
TI  - The efficacy and safety of inhaled fluticasone propionate/salmeterol and
      ipratropium/albuterol for the treatment of chronic obstructive pulmonary disease:
      an eight-week, multicenter, randomized, double-blind, double-dummy, parallel
      group study.
AB  - BACKGROUND: The pathology of chronic obstructive pulmonary disease (COPD)
      includes both obstructive and inflammatory components. OBJECTIVE: The aim of this
      study was to confirm the findings of a previous study that compared the efficacy
      of a combination of 2 short-acting bronchodilators with the use of an inhaled
      corticosteroid and a long-acting beta-agonist in the treatment of COPD. METHODS:
      We conducted an 8-week, multicenter, randomized, double-blind, double-dummy,
      parallel-group study of subjects with moderate to severe COPD to compare
      fluticasone propionate/salmeterol 250/50 microg BID (FSC) with
      ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure
      was morning preadministration forced expiratory volume in 1 second (FEV(1)).
      Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC,
      percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and
      overall daytime symptom score. Additional measures included sleep symptoms,
      supplemental albuterol use, and nighttime awakenings due to respiratory symptoms.
      Safety evaluations were based on clinical adverse events and COPD exacerbations.
      RESULTS: Baseline characteristics were similar between the FSC (n = 180) and
      IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively),
      mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean
      [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91%
      white), and sex (64% and 62% male). FSC resulted in greater improvements in
      morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P <
      0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024),
      percentage of symptom-free nights (P = 0.010), nighttime awakenings due to
      respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage
      of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021
      and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8
      increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001
      between groups). The type and incidence of adverse events were similar between
      the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%)
      subjects in the FSC and IB/ALB groups, respectively. CONCLUSION: In this 8-week
      study, subjects with moderate to severe COPD experienced greater improvements in
      lung function and symptom measures with FSC than with IB/ALB.

PMID- 15978303
TI  - Effectiveness of azelastine nasal spray compared with oral cetirizine in patients
      with seasonal allergic rhinitis.
AB  - BACKGROUND: Azelastine nasal spray and oral cetirizine are selective histamine
      H(1)-receptor antagonists that are approved in the United States for the
      treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: The objective of the
      present study was to compare the efficacy and tolerability of azelastine nasal
      spray administered at the recommended dosage of 2 sprays per nostril twice daily
      with those of cetirizine in the treatment of moderate to severe SAR. METHODS:
      This multicenter, randomized, double-blind, parallel-group, 2-week comparative
      study was conducted during the 2004 fall allergy season in patients with moderate
      to severe SAR. After a 1-week placebo lead-in period, patients were randomized to
      receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo
      tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray
      for the 2-week double-blind treatment period. The primary efficacy variables were
      (1) change from baseline to day 14 in the 12-hour reflective total nasal symptom
      score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and
      nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4
      hours after the first dose of study drug. During the double-blind treatment
      period, patients recorded their symptom scores on diary cards twice daily
      (morning and evening). Patients aged > or =18 years also completed the
      Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day
      14. RESULTS: Three hundred seven patients were randomized to treatment, and 299
      completed 2 weeks of study treatment. The age of the population ranged from 12 to
      74 years (mean, 35 years), 62.9% were female, and 69.6% were white. Over 2 weeks
      of treatment, both groups had significant improvements in the TNSS compared with
      baseline (P < 0.001). The overall change in TNSS was significantly greater with
      azelastine nasal spray compared with cetirizine (29.3% vs 23.0% improvement,
      respectively; P = 0.015). In terms of onset of action, azelastine nasal spray
      significantly improved the instantaneous TNSS compared with cetirizine at 60 and
      240 minutes after the initial dose (both, P = 0.040). Scores on each domain of
      the RQLQ were significantly improved in both groups compared with baseline (P <
      0.001); the overall RQLQ score was significantly improved with azelastine nasal
      spray compared with cetirizine (P = 0.049). Both treatments were well tolerated.
      CONCLUSION: In this 2-week study in patients with moderate to severe SAR,
      azelastine nasal spray was well tolerated and produced significantly greater
      improvements in TNSS and total RQLQ score compared with cetirizine.

PMID- 15978304
TI  - Metabolic effects of pioglitazone in combination with insulin in patients with
      type 2 diabetes mellitus whose disease is not adequately controlled with insulin
      therapy: results of a six-month, randomized, double-blind, prospective,
      multicenter, parallel-group study.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) is a progressive disease. Initial
      therapy begins with dietary and lifestyle modifications. However, as the disease
      progresses, glycemic control becomes more difficult to attain, often requiring >
      or =1 oral antihyperglycemic medication (OAM), and finally the addition of
      insulin to the OAMs and insulin monotherapy. OBJECTIVE: This study was designed
      to determine the effect of pioglitazone 30 mg plus insulin (PIO + INS) versus
      placebo plus insulin (PLB + INS) on glycemic control, the serum lipid profile,
      and selected cardiovascular risk factors in patients with type 2 DM whose disease
      was inadequately controlled with insulin therapy alone despite efforts to
      intensify such treatment. METHODS: This was a 6-month, randomized, double-blind,
      prospective, multicenter, placebo-controlled, parallel-group study. Patients with
      type 2 DM and a glycosylated hemoglobin (HbA(1c)) value > or =7.5% who were using
      insulin (with or without OAMs) entered a 3-month insulin intensification phase to
      achieve blood glucose targets with insulin monotherapy. After insulin
      intensification, those patients with HbA(1c) values > or =7.0% were randomized to
      PIO + INS or PLB + INS. The primary end point was the change in HbA(1c) from
      baseline. Cardiovascular risk markers (highly sensitive C-reactive protein [hs
      CRP] and plasminogen activator inhibitor-1 [PAI-1]) were measured at baseline and
      end point. RESULTS: Of the 289 patients randomized to treatment (mean [SD] age,
      58.9 [7.1] years; 164 women, 125 men), 142 received PIO + INS and 147 received
      PLB + INS. A total of 263 patients completed the study. After 6 months, PIO + INS
      reduced mean HbA(1c) (-0.69%; P < 0.002) and mean fasting plasma glucose ([FPG] 
      1.45 mmol/L; P < 0.002) from baseline. PLB + INS produced no significant changes
      in HbA(1c) or FPG. The between-treatment differences for HbA(1c) (-0.55%; P <
      0.002) and FPG (-1.80 mmol/L; P < 0.002) occurred despite a reduction of insulin
      dose in the PIO + INS group from baseline (-0.16 U/d . kg; P < 0.002).
      Significant between-group differences were observed for high-density lipoprotein
      cholesterol (0.13 mM; P < 0.002), triglycerides (ratio of geometric mean
      [PIO/PLB], 0.871; P < 0.01), atherogenic index of plasma (-0.11; P < 0.002), PAI
      1 (-5.10 U/mL; P < 0.001), and hs CRP (-1.47 mg/L; P < 0.05). The rate of
      clinical and biochemical hypoglycemia (blood glucose <2.8 mmol/L) did not differ
      statistically between treatment groups, but reported incidences of subjective
      hypoglycemia occurred more often with PIO + INS than with PLB + INS (90 vs 75; P
      < 0.05). Edema was more common with PIO + INS than with PLB + INS (20 vs 5
      instances, respectively), as was gain (mean [SEM]) in body weight (4.05 [4.03] vs
      0.20 [2.92] kg, respectively). CONCLUSION: Adding pioglitazone to insulin in
      these study patients with type 2 DM whose disease was inadequately controlled
      with insulin monotherapy further improved their glycemic control.

PMID- 15978305
TI  - A comparison of the clinical efficacy of pheniramine maleate/naphazoline
      hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic
      solution in the conjunctival allergen challenge model.
AB  - BACKGROUND: The signs and symptoms of allergic conjunctivitis include ocular
      redness and itching. Two treatment options currently indicated for acute ocular
      allergic reaction are pheniramine maleate 0.3%/naphazoline hydrochloride 0.025%
      ophthalmic solution, an over-the-counter antihistamine/vasoconstrictor
      combination; and olopatadine hydrochloride 0.1% ophthalmic solution, a
      prescription antihistamine/mast cell stabilizer. OBJECTIVE: This study was
      designed to compare, at onset of action, the relative effectiveness of
      pheniramine/naphazoline and olopatadine, when administered before conjunctival
      allergen challenge (CAC), using the ocular allergy index (OAI) as the primary end
      point. METHODS: This was a prospective, randomized, double-masked, contralateral,
      active- and placebo-controlled, single-center study of the CAC model. The first 2
      study visits established and confirmed the subjects' ocular allergic reaction (no
      medication administered). At visit 3, the subjects were randomly assigned to 1 of
      3 contralateral (right eye vs left eye) treatment combinations:
      pheniramine/naphazoline + olopatadine, pheniramine/naphazoline + placebo, or
      olopatadine + placebo. Medication was given 10 minutes before CAC. The subjects'
      erythema in the ciliary, conjunctival, and episcleral vessel beds; eyelid
      swelling; chemosis; and itching were evaluated at 7, 12, and 20 minutes after
      CAC. The OAI was calculated as a composite score of 6 signs and symptoms of
      allergic conjunctivitis to assess global severity. Between-treatment differences
      in OAI scores were used to evaluate efficacy. Subjects were asked their eye drop
      preference at the conclusion of visit 3. RESULTS: Subjects (n = 83) ranged in age
      from 20 to 70 years (mean, 42.5 years), 61.4% (n = 51) were female, and 94.0% (n
      = 78) were white. Both pheniramine/naphazoline and olopatadine were associated
      with significantly lower OAI scores than placebo at all 3 time points (all, P <
      0.001). OAI scores were significantly lower with pheniramine/naphazoline than
      with olopatadine at 12 and 20 minutes (P = 0.005 and P = 0.001, respectively).
      CONCLUSION: In this patient sample, studied in a CAC model of onset of action,
      prophylactic pheniramine/naphazoline was more effective than olopatadine and
      placebo in alleviating the signs and symptoms of the acute ocular allergic
      reaction, as measured by the OAI.

PMID- 15978306
TI  - Efficacy and tolerability of combination therapy with valsartan plus
      hydrochlorothiazide compared with amlodipine monotherapy in hypertensive patients
      with other cardiovascular risk factors: the VAST study.
AB  - BACKGROUND: Recent antihypertensive treatment guidelines recommend greater use of
      combination therapies. OBJECTIVES: The primary objective of this study was to
      determine whether combination therapy with valsartan 160 mg plus
      hydrochlorothiazide (HCTZ) 25 mg OD would be more effective than monotherapy with
      amlodipine 10 mg OD in reducing systolic blood pressure (SBP) in patients with
      moderate (stage II) hypertension and > or =1 other cardiovascular risk factor or
      concomitant condition. A secondary objective was to assess the effects of the
      study treatments on circulating markers of endothelial dysfunction and vascular
      inflammation. METHODS: This was a multicenter, randomized, double-blind, active
      controlled, 24-week study. After a 2-week, single-blind, placebo run-in period,
      patients were randomized to 3 groups, 2 of them receiving valsartan 160 mg OD and
      1 receiving amlodipine 5 mg OD. At week 4, HCTZ 12.5 mg OD was added to valsartan
      in one of the treatment groups (V+HCTZ12.5), HCTZ 25 mg OD was added to the other
      (V+HCTZ25), and the amlodipine dose was force-titrated to 10 mg OD (A10). The
      primary efficacy variable was change in mean sitting SBP at week 24. Other
      variables were changes in mean sitting diastolic blood pressure (DBP) and mean
      pulse pressure (PP) from baseline, and response rate (systolic response defined
      as mean sitting SBP <140 mm Hg or a reduction in mean sitting SBP of > or =20 mm
      Hg from baseline; diastolic response defined as mean sitting DBP <90 mm Hg or a
      reduction in mean sitting DBP of > or =10 mm Hg from baseline). Changes in the
      following markers of endothelial dysfunction were determined at baseline and
      weeks 4, 12, and 24 in all randomized patients from the participating European
      and South African centers: high-sensitivity C-reactive protein (hs-CRP),
      interleukin-6 (IL-6), vascular tissue plasminogen activator (t-PA) antigen, and
      oxidized low-density lipoprotein (LDL). RESULTS: The study enrolled 1088 patients
      with moderate hypertension (mean age, 61 years; 82% white; 53% women). The intent
      to-treat population consisted of 1079 patients: 357 in the V+HCTZ12.5 group, 363
      in the V+HCTZ25 group, and 359 in the A10 group. At baseline, the groups were
      comparable in terms of blood pressure and most other characteristics; the only
      statistically significant difference between groups was in the proportion of
      patients aged > or =65 years, which was lower in the amlodipine group (P = 0.01).
      At the end of the study, the least squares mean (SD) changes from baseline in
      mean sitting SBP were 27.1 (13.7), 29.7 (13.7), and 27.6 (13.8) mm Hg in the
      V+HCTZ12.5, V+HCTZ25, and A10 groups, respectively, with corresponding percent
      changes of 16%, 18%, and 17% (P < 0.05, V+HCTZ25 vs A10). The changes in mean
      sitting DBP did not differ significantly between groups. The reductions in PP
      were 17.5 (11.3), 18.7 (11.3), and 16.9 (11.3) mm Hg, with percent changes of
      24%, 26%, and 23% (P < 0.05, V+HCTZ25 vs A10). Significant reductions in t-PA
      antigen were observed in both combination-therapy groups compared with the
      amlodipine monotherapy group at week 12 (P < 0.05); the reductions remained
      significant through the end of the study in the V+HCTZ12.5 group. There was a
      significant reduction in IL-6 and hs-CRP at week 12 with V+HCTZ25 compared with
      A10 (P < 0.05). Oxidized LDL values were reduced by approximately 10% with all
      treatments. Rates of total adverse events were significantly lower with the
      valsartan-based treatments compared with amlodipine monotherapy (49.7%, 49.6%,
      and 67.5% with V+HCTZ12.5, V+HCTZ25, and A10, respectively; P < 0.05). Rates of
      total discontinuations were a respective 10.1%, 9.0%, and 24.5%, and
      discontinuation rates due to AEs were 4.2%, 3.5%, and 18.2%. Leg edema was more
      common with amlodipine monotherapy than with the valsartan-based combinations (P
      < 0.05). CONCLUSION: In this group of patients with moderate hypertension and >
      or =1 other cardiovascular risk factor or concomitant condition, similar and
      greater antihypertensive effects were seen with the fixed-dose combinations of
      valsartan 160 mg and HCTZ 12.5 and 25 mg OD, respectively, compared with
      amlodipine 10 mg OD, with significantly lower rates of treatment-related adverse
      events and possible beneficial effects on vascular markers.

PMID- 15978307
TI  - Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on
      propofol injection in the hand: a prospective, randomized, double-blind, vehicle
      controlled, dose-finding study in Japanese adult surgical patients.
AB  - BACKGROUND: Pain on injection is still a major problem with propofol used for
      general anesthesia. A number of techniques for reducing propofol-induced pain on
      injection have been tried, with variable results. Flurbiprofen axetil, a prodrug
      of the nonsteroidal anti-inflammatory drug flurbiprofen, has been used for
      postoperative pain management but has not been studied for managing pain on
      injection of propofol when preceded with venous occlusion. OBJECTIVE: The present
      study was undertaken to examine the efficacy of flurbiprofen axetil for reducing
      pain on propofol injection in Japanese adult surgical patients. METHODS: This
      prospective, randomized, double-blind, vehicle-controlled, dose-finding study was
      conducted at the Department of Anesthesiology, University of Tsukuba Institute of
      Clinical Medicine, Tsukuba, Japan. Japanese patients aged 18 to 65 years
      scheduled to undergo elective surgery were eligible. Patients were randomized to
      receive flurbiprofen axetil IV at 1 of 3 doses (25, 50, or 75 mg), or vehicle
      (control group), preceded by manual venous occlusion with a rubber tourniquet for
      2 minutes and followed by administration of 25% of the total calculated dose of
      propofol (2 mg/kg), injected into the largest vein of the hand through a 20-gauge
      IV cannula. During propofol injection, a researcher who was blinded to treatment
      assignment asked each patient about his or her pain at the injection site.
      Responses were scored on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 =
      severe). Median pain intensity scores in each group were determined. Adverse
      effects (AEs) at the injection site (pain, edema, wheal, or inflammation) were
      monitored for up to 24 hours after surgery. RESULTS: A total of 120 patients (62
      men, 58 women; mean [SD] age, 41 [12] years, mean [SD] height, 162 [8] cm; mean
      [SD] body weight, 58 [10] kg) were enrolled. Each treatment group comprised 30
      patients. No significant between-group differences in demographic characteristics
      were found. A significantly higher proportion of patients in the control group
      (77%) experienced pain compared with the flurbiprofen axetil 50- and 75-mg groups
      (47% and 43%, respectively; both, P < 0.01). The median pain intensity scores
      were significantly lower in the flurbiprofen axetil 50- and 75-mg groups (both, 0
      [no pain]) compared with controls (2 [moderate]; both, P < 0.01). The incidence
      and intensity of propofol-induced pain were statistically similar between the
      flurbiprofen axetil 25-mg and control groups. The incidence and intensity of pain
      associated with the injection of propofol were significantly lower in the
      flurbiprofen axetil 50- and 75-mg groups compared with the 25-mg group
      (incidence, 70% [both, P < 0.05]; median pain intensity score, 1 [mild] [both, P
      < 0.01]). No AEs were observed. CONCLUSION: In this study of Japanese adult
      surgical patients, flurbiprofen axetil at doses of 50 and 75 mg, preceded by
      venous occlusion for 2 minutes, was found to be effective in reducing propofol
      induced pain on injection.

PMID- 15978308
TI  - Oral absorption kinetics of levetiracetam: the effect of mixing with food or
      enteral nutrition formulas.
AB  - BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug with a favorable
      pharmacokinetic profile, including negligible protein binding and linear
      elimination kinetics. Because LEV is likely to be used in populations that
      include children and the elderly, alternative techniques of administration, such
      as crushing the tablet and mixing its contents with semisolid food or enteral
      nutrition formulas (ENFs), may be required in some clinical settings. Although
      previous studies have suggested that administration with food does not affect the
      overall absorption of LEV, there is a lack of data regarding concomitant
      administration with ENFs. OBJECTIVE: The objective of this study was to evaluate
      the oral absorption of LEV after concomitant administration with food or ENFs.
      METHODS: This was an unblinded, 3-way crossover study. After an overnight fast,
      subjects received a single dose of LEV 500 mg administered either as an intact
      tablet with 120 mL water (control, treatment A) or crushed and mixed with 4 oz
      applesauce (treatment B) or 120 mL of a common ENF (treatment C). All subjects
      received each treatment in a randomized sequence; there was a 7-day washout
      period between treatments. Serial blood samples were obtained over 24 hours for
      determination of the LEV serum concentration-time profile using gas
      chromatography with nitrogen phosphorus detection. AUC(0-24), C(max), and T(max)
      were calculated using noncompartmental methods and analyzed using analysis of
      variance. RESULTS: Ten healthy adult volunteers (6 men, 4 women) participated in
      the study (mean [SD] age, 28.9 [6.5] years; mean body weight, 78.6 [12.9] kg). No
      significant differences were noted between control and any other study treatment.
      Mean AUC values were 191.9 (50.2), 165.7 (43.4), and 168.3 (43.9) microg/mL . h
      for treatments A, B, and C, respectively. Mean T(max) values were 1.08 (0.65),
      1.32 (0.75), and 1.62 (0.73) hours, respectively. Mean C(max) values were 14.8
      (5.6), 12.1 (2.8), and 10.8 (2.0) microg/mL for the respective treatments. Mean
      LEV serum concentrations at 12 hours after dosing were similar for all study
      treatments (3.9, 4.1, and 4.0 microg/mL). The long-term stability of LEV in the
      various combinations was not assessed. CONCLUSIONS: In these healthy volunteers,
      the overall rate and extent of absorption of oral LEV were not significantly
      impaired after crushing and mixing of the tablet with either a food vehicle or a
      typical ENF product. The data suggest that peak serum concentrations of LEV may
      be slightly reduced after mixing with ENFs, although the difference was not
      significant compared with control values.

PMID- 15978309
TI  - Cefepime and continuous renal replacement therapy (CRRT): in vitro permeability
      of two CRRT membranes and pharmacokinetics in four critically ill patients.
AB  - BACKGROUND: Cefepime is a fourth-generation cephalosporin with a broad spectrum
      of antimicrobial activity against gram-positive and gram-negative micro
      organisms. It is a useful option for treating infections in critically ill
      patients in intensive care due to its high degree of activity and its
      tolerability. OBJECTIVE: The aim of this study was to characterize in vitro the
      permeability to cefepime of 2 membranes frequently used in continuous renal
      replacement therapies (CRRTs). An in vivo study was also carried out to determine
      the pharmacokinetics of cefepime in critically ill patients undergoing CRRT.
      METHODS: In vitro procedures were conducted in 3 different fluids using
      polyacrylonitrile (AN69) or polysulfone (PS) membranes. Continuous venovenous
      hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) were
      simulated. Four male patients undergoing CVVH or continuous venovenous
      hemodiafiltration, who received 2000 mg of cefepime intravenously every 8 hours,
      entered the in vivo study. Prefilter and ultrafiltrate samples were collected,
      and concentrations of cefepime were measured using high-performance liquid
      chromatography. The sieving coefficient (Sc), defined as the fraction of drug
      eliminated across the membrane, and the saturation coefficient (Sa), defined as
      the fraction of drug diffused through the membrane to the dialysate fluid, were
      analyzed. Pharmacokinetic parameters were determined according to a
      noncompartmental analysis. RESULTS: The patients ranged in age from 18 to 75
      years and weighed from 65 to 80 kg. By analyzing Sc and Sa values in the in vitro
      procedures, no differences were detected in the permeability of AN69 or PS
      membranes to cefepime in CVVH or CVVHD. Sc/Sa values were between 0.93 and 1.03
      in Ringer's lactate and in bovine albumin-containing Ringer's lactate samples,
      but Sc/Sa values were lower in plasma samples (0.82-0.95). In the in vivo portion
      of the study, the patients' mean (SD) Sc/Sa value was 0.76 (0.21) and correlated
      well with the fraction unbound to proteins (0.79 [0.09]). Clearance by CRRT (mean
      [SD]) was 29.0 (16.8)% of the total clearance. Serum elimination t(1/2) was 4.6
      (0.9) hours, and the volume of distribution at steady state was 0.6 (0.3) L/kg
      (mean [SD] values). CONCLUSIONS: Cefepime was significantly removed by CRRT. No
      significant differences were found in the Sc or Sa of cefepime between AN69 and
      PS membranes used in the CVVH or CVVHD procedures. The clearance of cefepime by
      CRRT must be considered when dosing critically ill patients.

PMID- 15978310
TI  - Comparison of actual and stated concentrations of pharmaceuticals manufactured in
      Mexico.
AB  - BACKGROUND: During the past 5 years, there has been much concern about the safety
      of and ease of access to drugs that are unavailable without a prescription in the
      United States but are manufactured and can be purchased over the counter (OTC) in
      Mexico. However, based on a literature search, studies have not been performed to
      determine whether such drugs meet the US Pharmacopoeia (USP) standards for
      percent of labeled amount. OBJECTIVE: The aim of this study was to determine
      whether 5 drugs commonly prescribed in the United States and manufactured and
      purchased in Mexico met USP standards for stated concentration, were properly
      packaged and sealed, and had properly labeled expiration dates and lot numbers.
      METHODS: For the study, we purchased acetaminophen, carbamazepine, diazepam,
      digoxin, and phenytoin from 2 to 4 pharmacies in Ciudad Acuna, Mexico. Samples of
      each drug, each with a different lot number, were purchased OTC or with a
      prescription. None of the pharmacists had knowledge of the study. Brand-name or
      generic drugs manufactured and obtained in the United States were also analyzed
      for comparative purposes. Each drug was analyzed by high-performance liquid
      chromatography using USP guidelines established for the analysis of each drug. In
      addition, we visually examined the packaging, seals, color, and appearance of the
      drugs, and observed whether the packages contained lot numbers and whether the
      drugs were within the stated expiration dates. RESULTS: For all 5 drugs, the 95%
      CIs fell within the USP-defined acceptable ranges for percent of labeled amount.
      This was found to be true for drugs obtained at different pharmacies, for
      different drug manufacturers, and for drugs with different lot numbers. All of
      the drugs were found to be properly packaged and sealed, had lot numbers listed
      on the packages, and were sold before the stated expiration dates. CONCLUSION:
      Although health care practitioners should be aware that patients might be using
      drugs manufactured and purchased in Mexico, the results of this study of a small
      sample of such drugs suggest they meet the USP standards for percent of labeled
      amount.

PMID- 15978311
TI  - Development of a population pharmacokinetic model for carbamazepine based on
      sparse therapeutic monitoring data from pediatric patients with epilepsy.
AB  - BACKGROUND: Population models can be important extensions of therapeutic drug
      monitoring (TDM), as they allow estimation of individual pharmacokinetic
      parameters based on a small number of measured drug concentrations. OBJECTIVE:
      This study used a Bayesian approach to explore the utility of routinely collected
      and sparse TDM data (1 sample per patient) for carbamazepine (CBZ) monotherapy in
      developing a population pharmacokinetic (PPK) model for CBZ in pediatric patients
      that would allow prediction of CBZ concentrations for both immediate- and
      controlled-release formulations. METHODS: Patient and TDM data were obtained from
      a pediatric neurology outpatient database. Data were analyzed using an iterative
      2-stage Bayesian algorithm and a nonparametric adaptive grid algorithm. Models
      were compared by final log likelihood, mean error (ME) as a measure of bias, and
      root mean squared error (RMSE) as a measure of precision. RESULTS: Fifty-seven
      entries with data on CBZ monotherapy were identified from the database and used
      in the analysis (36 from males, 21 from females; mean [SD] age, 9.1 [4.4] years
      [range, 2-21 years]). Preliminary models estimating clearance (Cl) or the
      elimination rate constant (K(el)) gave good prediction of serum concentrations
      compared with measured serum concentrations, but estimates of Cl and K(el) were
      highly correlated with estimates of volume of distribution (V(d)). Different
      covariate models were then tested. The selected model had zero-order input and
      had age and body weight as covariates. Cl (L/h) was calculated as K(el) . V(d),
      where K(el) = [K(i) - (K(s) . age)] and V(d) = [V(i) + (V(s) . body weight)].
      Median parameter estimates were V(i) (intercept) = 11.5 L (fixed); V(s) (slope) =
      0.3957 L/kg (range, 0.01200-1.5730); K(i) (intercept) = 0.173 h(-1) (fixed); and
      K(s) (slope) = 0.004487 h(-1) . y(-1) (range, 0.0001800-0.02969). The fit was
      good for estimates of steady-state serum concentrations based on prior values
      (population median estimates) (R = 0.468; R(2) = 0.219) but was even better for
      predictions based on individual Bayesian posterior values (R(2) = 0.991), with
      little bias (ME = -0.079) and good precision (RMSE = 0.055). CONCLUSIONS: Based
      on the findings of this study, sparse TDM data can be used for PPK modeling of
      CBZ clearance in children with epilepsy, and these models can be used to predict
      Cl at steady state in pediatric patients. However, to estimate additional
      pharmacokinetic model parameters (eg, the absorption rate constant and V(d)), it
      would be necessary to combine sparse TDM data with additional well-timed samples.
      This would allow development of more informative PPK models that could be used as
      part of Bayesian dose-individualization strategies.

PMID- 15978312
TI  - Physician prescribing and the hippocratic oath.

PMID- 15978313
TI  - Evaluating the effect on patient outcomes of appropriate and inappropriate use of
      beta-blockers as secondary prevention after myocardial infarction in a medicaid
      population.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is associated with high mortality
      in the United States. Beta-blockers have been shown to reduce mortality and
      reinfarction rates when used for long-term prevention after an AMI. However, this
      therapy is both underused and misused. The effect of this practice on outcomes
      needs to be investigated. OBJECTIVE: This study was undertaken to evaluate the
      effect on patient outcomes (ie, fatality, health care utilization, and costs) of
      appropriate and inappropriate prescribing of beta-blocker therapy after AMI in a
      Medicaid population aged <65 years. METHODS: Data for 1 year before and after AMI
      were extracted from West Virginia Medicaid claims from January 1, 1996, to June
      30, 2001. Information was obtained regarding prescriptions for beta-blockers for
      these patients within 90 days after discharge. Patients were divided into 2
      groups: those who were prescribed therapy appropriately and those who were
      prescribed therapy inappropriately (underuse or misuse). Fatality rates during 1
      year after discharge were compared using chi-square analysis. The study used
      regression analysis to model health care utilization and costs as a function of
      appropriately/inappropriately prescribed groups. RESULTS: Data were assessed for
      488 eligible patients (mean [SD] age, 53.70 [8.14] years; 246 men [50.4%], 242
      women [49.6%]). Overall, 309 patients (63.3%) had appropriate prescribing of beta
      blockers; at the end of 1 year, these patients had a significantly lower all
      cause death rate compared with those who were prescribed therapy inappropriately
      (P = 0.030). Although the cardiac death rate was slightly lower for the
      appropriate group, the difference was not statistically significant. The
      appropriately prescribed group had significantly higher health care utilization
      in the follow-up period (P < 0.050 for hospital visits, emergency department
      visits, and length of stay). These groups demonstrated differences in a few
      variables at baseline (age, presence of absolute contraindications, presence of
      hypertension, number of noncardiac admissions before AMI, and use of beta
      blockers before AMI: all, P < 0.050), implying different severity levels. Patient
      health status at the time of the incident AMI had a confounding effect on health
      care utilization, and there were indications that the appropriate group had
      greater severity compared with the inappropriate group. CONCLUSIONS: Appropriate
      prescribing of beta-blockers for secondary prevention after an AMI was associated
      with better survival in this population. However, the effects of inappropriate
      and appropriate beta-blocker prescribing on health care utilization need to be
      evaluated prospectively so that all severity indicators can be properly adjusted.

PMID- 15978314
TI  - Retrospective study of the costs of care during the first year of therapy with
      etanercept or infliximab among patients aged > or =65 years with rheumatoid
      arthritis.
AB  - OBJECTIVE: The aim of this work was to retrospectively examine the costs of
      therapy with etanercept and infliximab, among patients aged > or = 65 years with
      rheumatoid arthritis (RA), from a health-care system perspective. METHODS: Data
      from 2 large, automated US health-care claims databases (Constella COMPASS and
      Ingenix LabRx) were pooled for the analyses. Each database is comprised of paid
      facility, professional service, and retail (ie, outpatient) pharmacy claims from
      participating health plans. Using the 2 databases, all RA patients aged > =65
      years were identified who began therapy with etanercept or infliximab between
      July 1, 1999 (Constella COMPASS), or January 1, 2001 (Ingenix LabRx), and
      December 31, 2002. Costs of RA-related care (including study drugs, selected
      medications, and outpatient encounters for RA) and non-RA-related care (all other
      medications and services) for patients in the 2 treatment groups were assessed,
      in US dollars, over a 1-year period after therapy initiation. RESULTS: A total of
      280 RA patients aged > or = 65 years initiated therapy with etanercept (n = 99)
      or infliximab (n = 181) and met all other selection criteria. Etanercept patients
      were younger than infliximab patients (mean [SD] age, 70.5 [4.6] vs 71.8 [4.6]
      years; P = 0.04), were less likely to be enrolled in a managed care organization
      (76.7% vs 87.8%; P < 0.01), and had fewer pretreatment rheumatologist visits
      (mean [SD], 1.3 [2.3] vs 2.2 [3.8]; P = 0.04). Other characteristics, including
      pretreatment levels of other types of health-care utilization, were generally
      similar. Mean (95% CI) total cost of RA-related care was lower for etanercept
      patients in both databases (US 12,159 dollars [US 10,795 dollars-US 13,380
      dollars] for etanercept vs US 22,347 dollars [US 20,808 dollars-US 23,912
      dollars] for infliximab in one, and US 14,297 [US 12,238 dollars-US 16,326
      dollars] for etanercept vs US 22,154 dollars [US 19,688 dollars-US 24,703
      dollars] for infliximab in the other), primarily due to lower costs of anti-tumor
      necrosis factor therapy (US 10,015 dollars [US 8754 dollars-US 11,224 dollars]
      for etanercept vs US 18,611 dollars [US 17,169 dollars-US 20,023 dollars] for
      infliximab in one database; US 11,917 dollars [US 10,128 dollars-US 13,480
      dollars] for etanercept vs US 16,759 dollars [US 14,551 dollars-US 19,062
      dollars] for infliximab in the other). Mean (95% CI) costs of non-RA-related care
      were similar among etanercept and infliximab patients in both databases (US
      13,100 dollars [US 8956 dollars-US 18,377 dollars] for etanercept vs US 11,789
      dollars [US 8326 dollars-US 16,001 dollars] for infliximab in one, and US 16,665
      dollars [US 10,329 dollars-US 25,690 dollars] for etanercept vs US 13,959 dollars
      [US 10,216 dollars-US 18,168 dollars] for infliximab in the other). CONCLUSION:
      These results suggest that costs of RA-related care during the first year of
      therapy may be lower among RA patients aged > or =65 years receiving etanercept
      versus infliximab, a difference attributable primarily to lower costs of drug
      acquisition.

PMID- 15978315
TI  - Silencing nature's narcotics: metabolic engineering of the opium poppy.
AB  - The opium poppy, Papaver somniferum L., and its narcotic and analgesic alkaloids,
      have an ancient history of use (and abuse) by humankind. A recent article by
      Allen and co-workers describes the metabolic engineering of morphine biosynthesis
      to block morphine formation and accumulate a potentially valuable pathway
      intermediate, (S)-reticuline. This work highlights the potential for modifying
      the production of pharmaceuticals in plants, but also raises questions about the
      complex regulation of biosynthetic pathways.

PMID- 15978316
TI  - Creating new specific ligand-receptor pairs for transgene regulation.
AB  - The creation of specifically matched ligand-receptor pairs that are orthogonal to
      naturally present interacting pairs is essential for the development of small
      molecule-regulated gene expression systems for biotechnological applications.
      However, for many years this task has represented a significant challenge for
      synthetic chemists and protein engineers. Recently, Doyle and colleagues
      demonstrated that highly specific ligand-receptor pairs can be engineered in a
      rapid fashion by creating large libraries of protein variants and applying a
      selection scheme to identify variants with improved activation by the target
      synthetic ligand.

PMID- 15978317
TI  - Crop biotechnology provides an opportunity to develop a sustainable future.
AB  - The current reliance on petro-based fuels and chemicals is not sustainable. New
      technologies typically take approximately 25 years to penetrate the market;
      consequently, the development of viable alternatives is required in the near
      future. Plant-based systems capture solar energy and can be produced in a
      renewable manner. However, the harvestable parts are not well optimized for
      energy transfer and this has been a significant limitation to the development of
      economically viable and sustainable biomass energy systems. Biotechnology has
      provided a new toolset that can be used to design and optimize the capture of
      solar energy through crops. Further development of biotechnology and genomics
      tools will enable the development of crops with specific traits that are
      optimized for biofuels and bioenergy. The implementation of such a system will
      enable a sustainable platform for centuries to come and should be given a high
      priority in society.

PMID- 15978318
TI  - Robotic spotting of cDNA and oligonucleotide microarrays.
AB  - DNA microarrays are a uniquely efficient method for simultaneously assessing the
      expression levels of thousands of genes. Owing to their flexibility and value,
      mechanically spotted microarrays remain the most popular platform. Here, we
      review recent technological advances with a focus on spotted arrays. Robotic
      spotting still poses numerous technical challenges. To reduce artefacts, many
      laboratories have recently investigated ways of improving the spotting process.
      We compare alternative options and discuss implications for next-generation
      systems. Together with modern approaches to data analysis, such developments
      bring greatly improved reliability to individual microarray experiments.
      Advancing towards the ultimate goal of delivering calibrated, truly quantitative
      gene-expression measurements on a genomic scale, microarray technology remains at
      the forefront of post-genomic systems biology.

PMID- 15978320
TI  - On a form of chronic tendovaginitis. (Translated article: Cor-Bl.f.schweiz.
      Aerzrte 1895:25:389-94).

PMID- 15978319
TI  - The anatomy lesson of Dr Tulp.
AB  - The anatomy lesson of Dr Tulp is one of the most famous paintings by Rembrandt. A
      detailed examination of the scene leads us to believe that Dr Tulp was
      demonstrating the function of the flexor digitorum superficialis. Therefore, the
      painting is a true lesson in physiology which is in keeping with the spirit of
      the 17th century, which was the century in which the modern theory of movement in
      physics evolved. The anatomy lesson of Dr Tulp also symbolizes the break with the
      descriptive anatomy of Vesalius which occurred during this century.

PMID- 15978321
TI  - On the nature and treatment of stenosing tendovaginitis on the styloid process of
      the radius. (Translated article: Muenchener Medizinische Wochenschrift 1912, 59,
      5-6).

PMID- 15978322
TI  - Sonic hedgehog signaling in basal cell carcinomas.
AB  - The development of basal cell carcinoma, the commonest human cancer in fair
      skinned populations, is clearly associated with constitutive activation of sonic
      hedgehog signaling. Insight into the genesis of BCC came from the identification
      of germline mutations of the tumor suppressor gene, PATCHED, a key regulatory
      component of hedgehog signaling in the nevoid basal cell carcinoma syndrome.
      Analysis of sporadic basal cell carcinomas and those from repair deficient
      xeroderma pigmentosum patients has revealed mutational inactivation of PATCHED
      and gain of function mutations of the proto-oncogenes, SMOOTHENED and SONIC
      HEDGEHOG associated with solar UV exposure. The molecular mechanisms involved in
      alterations of the hedgehog signaling pathway that lead to the formation of basal
      cell carcinomas are being unraveled and has already allowed the investigation of
      future therapeutic strategies for treating these skin cancers.

PMID- 15978323
TI  - Correlation between reduction potentials and inhibitory effects on Epstein-Barr
      virus activation of poly-substituted anthraquinones.
AB  - As a continuation of our studies using natural and synthetic products as cancer
      chemopreventive agents, we examined the reduction potentials of some poly
      substituted anthraquinones in phosphate buffer at pH 7.2 by means of cyclic
      voltammetry. A definite correlation has been found between the reduction
      potentials and the inhibitory effects of the poly-substituted anthraquinones on
      Epstein-Barr virus early antigen activation. It has been further shown that the
      correlation can be enhanced by introducing log P as an additional parameter.

PMID- 15978324
TI  - Ras/MAP kinase pathways are involved in Ras specific apoptosis induced by sodium
      butyrate.
AB  - Histone deacetylase inhibitors such as TSA, SAHA, and NaBu etc. are prospective
      cancer therapeutics of growing interest. Here, we demonstrated that oncogenic ras
      transformed rat liver epithelial (WB-ras) cells were specifically undergone
      apoptosis by 48 h treatment of NaBu. During this, inhibition of ras proteins,
      especially farnesylated form of ras, and down-regulation of ERK1/2 were observed,
      which suggest ras/raf/MEK/ERK down-regulation, while p38 MAP kinase was
      maintained up-regulated. In addition, up-regulation of pro-apoptotic proteins
      such as p53 and p21CIP1/WAF1, and down-regulation of cell cycle regulator/anti
      apoptotic proteins such as cdk2, -4 and phosphorylated Akt were observed
      concurrently with an increase in apoptotic cell portion. A phosphatase inhibitor,
      sodium orthovanadate (SOV), efficiently blocked apoptosis and restored
      responsible proteins for each phenomenon including ERK1/2 while SB203580, a
      specific p38 MAP kinase inhibitor, showed minor effect on them. Thus, ras/ERK
      signaling pathway can be considered in chemotherapeutic strategies of NaBu
      regardless of its inhibitory action on histone deacetylase.

PMID- 15978325
TI  - Association of polymorphism of IL-10 and TNF-A genes with gastric cancer in
      Korea.
AB  - We performed this study to determine the role of polymorphisms of the IL-10 and
      TNF-alpha promoter genes in the carcinogenesis/pathogenesis of gastric cancer
      (GC) and peptic ulcer diseases (PUD) in Korea. A total of 232 patients with
      gastric diseases and 120 healthy controls were included. Polymorphisms of IL-10
      1082/-592 gene and TNF-A-308 gene were genotyped by PCR-RFLP. There were no
      differences in genotypes and allele frequencies of IL-10 and TNF-A polymorphism
      between study group with GC or PUD and control group. In addition, there were no
      differences in genotypic frequencies according to H. pylori infection status,
      location of GC, and histologic type of GC. In conclusion, IL-10-1082/-592 and TNF
      A-308 genetic polymorphisms may not be the important contributors to GC in Korea.

PMID- 15978326
TI  - Characteristics of complement activation in mice bearing Lewis lung carcinomas
      treated by photodynamic therapy.
AB  - Following treatment of Lewis lung carcinomas (LLC) by Photofrin-mediated
      photodynamic therapy (PDT), tumor tissues and sera of host mice were collected
      for the analysis of complement activity. Elevated tumor C3 levels were detected
      between 1 and 24 h after PDT, while serum C3 levels increased significantly at 24
      h post therapy. Increased alternative complement pathway activity in the serum
      was evident between 1 and 3 days post PDT. Blocking C3a- or C5a-receptors in the
      host mice decreased the efficacy of PDT in producing LLC tumor cures, supporting
      the importance of complement action in PDT-mediated tumor destruction.

PMID- 15978327
TI  - Production and characterization of an active single-chain variable fragment
      antibody recognizing CD25.
AB  - The alpha subunit of the interleukin-2 receptor (IL-2Ralpha, CD25) is a potential
      target in therapeutic approaches for hematolopoietic malignancies expressing CD25
      on their cell surface, such as adult T cell leukemia/lymphomas. Recent reports
      have demonstrated that depletion of CD4+CD25+ regulatory T cells with anti-CD25
      antibodies may enhance host tumor immunity. We previously raised a mouse
      monoclonal antibody (mAb), Ta60b mAb (IgG1kappa), specifically recognizing CD25,
      and an attempt was made here to produce a single chain Fv fragment (scFv) from
      this mAb as an initial step to development of scFv-based therapeutics. cDNA
      fragments encoding for the variable regions of the light and heavy chains of the
      Ta60b mAb were thus isolated by polymerase chain reaction-mediated cloning, and,
      an expression vector constructed to express Ta60b scFv fused with the maltose
      binding protein (MBP) in the periplasm of Escherichia coli. The soluble form of
      MBP-Ta60b fused scFv could be extracted and affinity-purified with an
      amylose/agarose column, allowing its immunoreactivity to be analyzed by enzyme
      linked immunosorbent assay (ELISA), mixed hemadsorption assay, and fluorescence
      activated cell sorting. In addition, binding activity was studied by competitive
      ELISA and surface plasmon resonance. The results showed that Ta60b scFv obtained
      from periplasm retains good reactivity, although its KD value was 4-fold lower
      than that of the whole Ta60b antibody, suggesting possible clinical use for
      treatment of patients with CD25-expressing tumors and also for enhancing anti
      tumor immunity.

PMID- 15978328
TI  - Quantification of C13orf19/P38IP mRNA expression by quantitative real-time PCR in
      patients with urological malignancies.
AB  - Quantitative real-time PCR was performed for C13orf19, a gene located on
      chromosome 13q and previously described to be down-regulated in prostate
      carcinoma, on different cancer cell lines, on matched prostate tissues from 61
      patients with prostate carcinoma and on matched kidney tissues from 23 patients
      with renal clear cell carcinoma. All data were normalized to glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), porphobilinogen deaminase (PBGD) and
      hypoxanthine guanine phosphoribosyl transferase (HPRT) mRNA expression. A
      C13orf19 quantitative PCR (QPCR) showed the mRNA to be down-regulated in matched
      prostate tissues (P=0.007 and lower, paired Student's t-test). However, an at
      least 1.5-fold C13orf19 mRNA downregulation was observed in samples from 28
      patients (46%) and an at least 1.5-fold upregulation was observed in samples from
      17 patients (28%). In contrast, C13orf19 mRNA alterations in expression seemed to
      be random events in kidney cancers.

PMID- 15978329
TI  - Stromal cell-derived factor-1 (SDF-1) alleles and susceptibility to breast
      carcinoma.
AB  - Stromal cell-Derived Factor-1 (SDF-1, CXCL12) is one the ELR- CXC angiogenic
      chemokines. It contributes to hematopoiesis and lymphocyte trafficking. SDF-1 and
      its exclusive receptor, CXCR4, are reported to play important roles in tumor
      growth, angiogenesis and metastasis of different types of tumors such as breast,
      lung, prostate and pancreatic cancers. SDF-1 gene polymorphism, known as SDF1
      3'A, has been investigated in HIV-1 infection and the incidence of breast cancer.
      This investigation was aimed to study the frequency of SDF1-3'A mutation in
      Iranian women with breast cancer. Results showed that the frequency of AA and AG
      genotypes was higher among patients, while the frequency of GG genotype was lower
      compared to the controls. Thus AA and AG genotypes of SDF-1 may be considered as
      factors increasing the susceptibility of Iranian women to breast cancer.

PMID- 15978330
TI  - Increased expression of mRNA specific for thymidine kinase, deoxycytidine kinase
      or thymidine phosphorylase in human papillary thyroid carcinoma.
AB  - The aim of the present study was to estimate the expression of mRNA, specific for
      thymidine kinase 1 (TK1), deoxycytidine kinase (dCK), and thymidine phosphorylase
      (dThdPase), i.e. enzymes involved in pyrimidine and purine metabolism in human
      papillary thyroid carcinoma (PTC) tissue. Additionally, the expression of dCK was
      estimated, in medullary thyroid carcinoma (MTC). For control, the RNA expression
      levels for all the enzymes were measured in macroscopically unchanged thyroid
      tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) and densitometry
      were employed for mRNA expression measurements, with the beta-actin gene as a
      control housekeeping gene. The levels of mRNA expression for TK1, dCK and
      dThdPase in human PTC, as well as mRNA expression for dCK in MTC, were
      significantly higher than mRNA expressions for those enzymes found in
      macroscopically unchanged thyroid tissue. It is concluded that an increased
      expression of mRNA, specific for TK1, dCK and dThdPase, may be involved in
      carcinogenic processes in the human thyroid.

PMID- 15978331
TI  - CYP3A5 genotypes and risk of oesophageal cancer in two South African populations.
AB  - CYP3A5 is the major cytochrome P450 enzyme in the oesophagus and metabolises many
      potentially carcinogenic compounds. The frequencies of CYP3A5 allelic variants,
      CYP3A5*2, *3, *6 and *7 which code for enzymes with severely decreased activities
      were compared between 241 oesophageal cancer patients and 272 controls in Black
      and Mixed Ancestry South Africans. A significantly higher frequency of CYP3A5*3
      was observed in the controls compared to patients amongst the Mixed Ancestry
      group (P=0.025). Individuals homozygous for defective CYP3A5 had reduced risk of
      developing oesophageal cancer (P=0.032).

PMID- 15978332
TI  - Prognostic role of cyclooxygenase-2 expression in esophageal carcinoma.
AB  - Cyclooxygenase-2 (COX-2) is involved in esophageal carcinogenesis, but its
      clinical significance is not clarified yet. The association of several
      clinicopathological parameters with the immunohistochemical expression of COX-2
      was analyzed in paraffin-embedded esophageal cancer specimens. In
      adenocarcinomas, COX-2 upregulation showed to be a late event and in a
      multivariate analysis it was associated independently with a reduced survival
      after surgery compared with low COX-2 expressed tumors (P=0.02). Although, the
      expression was extensively high in well-differentiated parts of squamous cell
      carcinoma, it was not related with a poor outcome. This study supports further
      investigation of selective COX-2 inhibitors in these tumors.

PMID- 15978333
TI  - Non-random structural chromosomal changes in primary gastric cancer.
AB  - Gastric cancer is of major importance world-wide representing the second most
      common cause of cancer related death in the world. Data concerning the
      chromosomal changes in gastric cancer are limited and no specific change has been
      identified to date. We have studied cytogenetically 15 cases of primary gastric
      cancer by direct culture of tumors cells and G-banding technique. We focused on
      structural aberrations observed in order to identify non-random aberrations
      presenting common chromosomal breakpoints. Chromosomes most commonly involved
      were according to frequency 1,11,14,7,17,6,8 and 13. Chromosome 11 was involved
      as add(11)(p15), while the pericentromeric area of chromosome 14 was constantly
      participated in aberrations. Isochromosomes i(1q), i(8q), i(13q), i(14q) and
      i(17q) were constantly found. Furthermore translocations t(1;7), t(7;14), t(6;17)
      and t(5;14) were identified. Conventional cytogenetics continues to be valuable
      in cancer study detecting genomic areas potentially candidate for the isolation
      of genes related to carcinogenesis.

PMID- 15978335
TI  - Facial soft tissue thickness in Japanese female children.
AB  - Facial reconstruction techniques used in forensic anthropology are based on soft
      tissue thickness measurements. Many studies of facial tissue thickness in adults
      have been published that take racial background into account. However, the only
      data on facial thickness in children are derived from studies of American,
      British, and Hispanic children. The authors therefore measured facial tissue
      thickness in Japanese children, with the aim of providing data for producing
      accurate facial likenesses and to evaluate matching of skull-photo
      superimposition images. Cephalometric X-ray images give an approximately 10%
      enlargement from true size and can demonstrate the relationship between soft and
      hard tissue. Facial soft tissue thickness was measured at 12 anthropological
      points using X-ray cephalometry.

PMID- 15978334
TI  - Hypoxia-induced tumor angiogenic pathway in head and neck cancer: an in vivo
      study.
AB  - Numerous studies indicate the importance of hypoxia-induced pathway in tumor
      angiogenesis, but in vivo studies examining the importance of this mechanism in
      prognosis of patients with head and neck squamous cell carcinoma present
      conflicting results. We performed a retrospective analysis of 81 patients with
      head and neck squamous cell carcinoma in order to investigate whether hypoxia
      inducible factor 1a (HIF-1a) immunohistochemical expression correlates with
      vascular endothelial growth factor (VEGF) expression and clinicopathologic
      parameters or prognosis. Our results showed a statistically significant
      association between HIF-1a and VEGF expression in tumors located in the lower lip
      and in larynx, but not in those located in the oral cavity. HIF-1a expression had
      no impact on prognosis, while VEGF expression correlated significantly with
      adverse prognosis. These findings support the hypothesis that tumor angiogenesis
      is close related, but not strictly dependent, on the hypoxic conditions of
      tumor's microenvironment.

PMID- 15978336
TI  - Identification of DNA of human origin based on amplification of human-specific
      mitochondrial cytochrome b region.
AB  - Species-specific differences in a non-polymorphic region of the mitochondrial
      cytochrome b gene appear to be large enough to allow human-specific amplification
      of forensic DNA samples. We therefore developed a PCR-based method using newly
      designed primers to amplify a 157-bp portion of the human mitochondrial
      cytochrome b gene. The forward and reverse primers were designed to hybridize to
      regions of the human mitochondrial cytochrome b gene with sequences differing
      from those of chimpanzee by 26% (7 bp/27 bp) and 26% (6 bp/23 bp), respectively.
      Using this primer pair, we successfully amplified DNA extracted from blood
      samples of 48 healthy adults. All these human samples produced a single band of
      the expected size on agarose gel electrophoresis, and the sequence of the single
      band was shown to be identical to that of the target region (157 bp) by sequence
      analysis. On the other hand, no visible bands were amplified from DNA extracted
      from blood samples of animals including non-human primates (chimpanzee, gorilla,
      Japanese monkey, crab-eating monkey) and other species (cow, pig, dog, goat, rat,
      chicken and tuna). Thus, DNA producing a single band following PCR amplification
      using this primer pair can be reasonably interpreted as being of human origin. In
      addition, aged biological specimens comprising bloodstains, hair shafts and bones
      were successfully identified as being of human origin, illustrating the
      applicability of the present method to forensic specimens.

PMID- 15978337
TI  - Relatedness and DNA: are we taking it seriously enough?
AB  - In forensic DNA testimony most DNA laboratories report the match probability for
      an unrelated person from some relevant population. These laboratories typically
      make available the match probability for relatives when requested. This practice
      has served well for many years. However, as the discrimination power of our
      multiplexes has increased the estimated match probabilities for both related and
      unrelated people have become markedly smaller. Associated with this general
      reduction in match probabilities have been the observations that the relative
      balance between the match probabilities of the many unrelated people and the few
      relatives of a suspect has changed. We suggest that we should now report
      routinely the match probability for a sibling whenever the suspect has a non
      excluded sibling.

PMID- 15978338
TI  - A molecular identification system for grasses: a novel technology for forensic
      botany.
AB  - Our present inability to rapidly, accurately and cost-effectively identify trace
      botanical evidence remains the major impediment to the routine application of
      forensic botany. Grasses are amongst the most likely plant species encountered as
      forensic trace evidence and have the potential to provide links between crime
      scenes and individuals or other vital crime scene information. We are designing a
      molecular DNA-based identification system for grasses consisting of several PCR
      assays that, like a traditional morphological taxonomic key, provide criteria
      that progressively identify an unknown grass sample to a given taxonomic rank. In
      a prior study of DNA sequences across 20 phylogenetically representative grass
      species, we identified a series of potentially informative indels in the grass
      mitochondrial genome. In this study we designed and tested five PCR assays
      spanning these indels and assessed the feasibility of these assays to aid
      identification of unknown grass samples. We confirmed that for our control set of
      20 samples, on which the design of the PCR assays was based, the five primer
      combinations produced the expected results. Using these PCR assays in a 'blind
      test', we were able to identify 25 unknown grass samples with some restrictions.
      Species belonging to genera represented in our control set were all correctly
      identified to genus with one exception. Similarly, genera belonging to tribes in
      the control set were correctly identified to the tribal level. Finally, for those
      samples for which neither the tribal or genus specific PCR assays were designed,
      we could confidently exclude these samples from belonging to certain tribes and
      genera. The results confirmed the utility of the PCR assays and the feasibility
      of developing a robust full-scale usable grass identification system for forensic
      purposes.

PMID- 15978339
TI  - Forensic evaluation and haplotypes of 19 Y-chromosomal STR loci in Koreans.
AB  - In this study, 19 Y-specific STR loci (DYS19, DYS389I/II, DYS390, DYS391, DYS392,
      DYS393, DYS385, DYS388, DYS434, DYS435, DYS436, DYS437, DYS438, DYS439, DYS446,
      DYS449, and DYS464) were analyzed in 301 unrelated Korean males by three
      multiplex PCR systems. The haplotype diversity using the classical set of Y-STRs
      (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, and DYS385; multiplex I) was
      0.9963. For the same individuals, the haplotype diversity value using the new set
      of highly informative Y-STRs (DYS385, DYS446, DYS449, and DYS464; multiplex III)
      was 0.9989, while that using the combined set of Y-STRs by adding DYS388 to the
      previously studied DYS434, DYS435, DYS436, DYS437, DYS438, and DYS439 (multiplex
      II) was 0.9509. A total of 297 different haplotypes were identified using the 19
      Y-STR markers, of which 293 were unique and 4 were found twice. The overall
      haplotype diversity was 0.9999. The evaluation of the information of selected
      markers by combination of each marker with the minimal haplotype showed that
      DYS434, DYS435, DYS436, DYS437, and DYS438 do not significantly contribute to
      increment of haplotype diversity. However, respective conjunction of DYS464,
      DYS449, and DYS446 with the minimal haplotype considerably increased the
      haplotype diversity. Especially, DYS464 is expected to be the most useful marker
      that can be included in the expanded minimal haplotype. These results including
      the haplotype data at 19 Y-STR loci in the present study would provide useful
      information in forensic practice in a Korean population.

PMID- 15978340
TI  - Driving under the influence of drugs -- evaluation of analytical data of drugs in
      oral fluid, serum and urine, and correlation with impairment symptoms.
AB  - A study was performed to acquire urine, serum and oral fluid samples in cases of
      suspected driving under the influence of drugs of abuse. Oral fluid was collected
      using a novel sampling/testing device (Drager DrugTest System). The aim of the
      study was to evaluate oral fluid and urine as a predictor of blood samples
      positive for drugs and impairment symptoms. Analysis for cannabinoids,
      amphetamine and its derivatives, opiates and cocaine was performed in urine using
      the Mahsan Kombi/DOA4-test, in serum using immunoassay and gas chromatography
      mass spectrometry (GC-MS) confirmation and in oral fluid by GC-MS. Police and
      medical officer observations of impairment symptoms were rated and evaluated
      using a threshold value for the classification of driving inability. Accuracy in
      correlating drug detection in oral fluid and serum were >90% for all substances
      and also >90% in urine and serum except for THC (71.0%). Of the cases with oral
      fluid positive for any drug 97.1% of corresponding serum samples were also
      positive for at least one drug; of drug-positive urine samples this were only
      82.4%. In 119 of 146 cases, impairment symptoms above threshold were observed
      (81.5%). Of the cases with drugs detected in serum, 19.1% appeared not impaired
      which were the same with drug-positive oral fluid while more persons with drug
      positive urine samples appeared uninfluenced (32.7%). The data demonstrate that
      oral fluid is superior to urine in correlating with serum analytical data and
      impairment symptoms of drivers under the influence of drugs of abuse.

PMID- 15978341
TI  - Some pyridine derivatives as "route-specific markers" in 4-methoxyamphetamine
      (PMA) prepared by the Leuckart Method Studies on the role of the aminating agent
      in their distribution in the final product.
AB  - The two previously unknown isomeric aryl-methylpyridines were prepared and
      analysed. Both 2,6-dimethyl-3,5-(4'-methoxyphenyl)pyridine and 2,4-dimethyl-3,5
      di-(4'-methoxyphenyl)pyridine have been identified as a new by-product in the
      crude 4-methoxyamphetamine (PMA) obtained via the Leuckart method. The synthesis
      of 2,6-dimethyl-3,5-diphenylpyridine, which is connected to amphetamine
      chemistry, is also reported. It was also found that different reagents
      (formamide, formamide/HCOOH, ammonium formate) used in the course of the Leuckart
      synthesis of PMA significantly affected the impurity content. The presented
      results point out on the "high-boiling pyridines" as compounds especially useful
      in the comparative analysis, since their profile seems to be independent on the
      purification procedure and may be conveyed from the crude reaction mixture even
      into a carefully purified final product.

PMID- 15978342
TI  - Determination of synthesis method of ecstasy based on the basic impurities.
AB  - MDMA was prepared by five different synthesis routes, i.e. by dissolving metal
      reduction (Al/Hg), cyanoborohydride reduction (NaBH(3)CN), borohydride reduction
      in low temperature (NaBH(4)), Leuckart reaction and safrole bromination. MDP-2-P
      was prepared by two different synthesis methods, i.e. by isosafrole oxidation and
      MDP-2-nitropropene reduction. Each of the synthesis routes was repeated three
      times in order to establish variation in qualitative composition of route
      specific impurities between different batches. The analysis of impurities in MDP
      2-nitropropene, MDP-2-P, bromosafrole and MDMA was performed with GC-MS. GC/MS
      was used also in the analysis of impurities in starting materials: safrole,
      isosafrole and piperonal. As a result of our study the way of determination of
      MDMA synthesis route determination based on qualitative composition of impurities
      is proposed.

PMID- 15978343
TI  - Chemical characterization of counterfeit captagon tablets seized in Jordan.
AB  - Fenethylline, commonly known by the trademark name 'captagon', is one of the most
      popular drugs of abuse among the young affluent communities of the Middle East.
      The Drug Control Department of the Public Security Directorate of Jordan has put
      captagon under control in the year 1988. Samples from 124 batches seized were
      analyzed by means of gas chromatograph-mass spectrometry (GC-MS). The analysis
      demonstrates the presence of amphetamine, caffeine and several other substances,
      besides, the absence of fenethylline. Based on GC-MS analytical data, comparisons
      were made between the various samples to determine the similarities and obtain
      inferences with respect to commonality of origin.

PMID- 15978344
TI  - Raman spectroscopy and the forensic analysis of black/grey and blue cotton fibres
      Part 1: investigation of the effects of varying laser wavelength.
AB  - Raman spectroscopy was investigated to determine the optimal conditions, mainly
      laser wavelength/s, for the analysis of the commonly encountered black/grey and
      blue cotton fibres dyed with reactive dyes. In this first part, a single blue
      cotton fibre, its three dye components, and an undyed cotton fibre were analysed
      with five different laser wavelengths from two different Raman microprobe
      spectrometers. The quality of the spectra, fibre degradation and speed of
      acquisition were used to determine that, under the conditions used, the 785 and
      830 nm lasers gave superior results. The 632.8 nm laser wavelengths provided good
      results with little acquisition time and no spectral degradation. Results
      indicate that, at least, the major dye component could be identified using Raman
      spectroscopy.

PMID- 15978345
TI  - Rapid and simple method for direct determination of several amphetamines in
      seized tablets by GC--FID.
AB  - A simple and rapid method for direct simultaneous determination of amphetamine,
      methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4
      methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine
      (MDEA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in seized
      tablets was developed using gas chromatography with flame ionization detection.
      Separation of all six underivatized amphetamines, including diphenylamine as
      internal standard, was performed in about 6 min, using SPB-50 capillary column.
      Amphetamine and methamphetamine eluted with negligible tailing while the other
      amphetamines had highly symmetrical peaks. Sensitivity per component on-column
      was in the nanogram range, and reproducibility from 2.6 to 6.6% at low
      concentration (2.4 microg/mL) and from 1.2 to 2.6% at high (70 microg/mL)
      concentration. The method has a wide linear range, from Limit of detection (LOD)
      to almost 200 microg/mL, thus allowing analysis of different samples across a
      wide range of possible concentrations of amphetamines. This simple, fast and
      precise method using gas chromatography--flame ionization detector (GC--FID), in
      conjunction with other methods (TLC, IR, HPLC), can be used for identification of
      amphetamines and direct determination in seized tablets, especially in
      laboratories with heavy workload.

PMID- 15978346
TI  - Determination of the hand from single digit fingerprint: a study of whorls.
AB  - In this investigation 400 bilateral rolled fingerprints of Punjabi Jat males have
      been examined for the determination of the hand from single digit fingerprint
      from whorl patterns. Direction of the flow of the apex ridges, rotation of
      centrally circular ridges, angles between the core and the delta, ridge tracing,
      ridge counting and the position of the perpendiculars drawn between the delta and
      the core are useful for establishing in most of the cases the hand and finger
      involved from the fingers having whorl pattern.

PMID- 15978347
TI  - Forensic interpretation of Y-chromosomal DNA mixtures.
AB  - The mathematical concept previously introduced for the forensic interpretation of
      DNA mixtures using non-associated genetic markers has been adapted to the
      assessment of haplotypes. Such calculus is required, for example, when Y
      chromosomal markers are used in forensics. In addition to outlining the general
      mathematical framework, we devise two approaches to its practical computational
      implementation, involving either the inclusion-exclusion principle of probability
      theory or a recursion in the number of unknown contributors invoked. The two
      approaches scale differently, depending upon the complexity of the case and the
      diversity of the markers used. The performance of Y-chromosomal microsatellites
      (Y-STRs) as a means of trace donor discrimination has been assessed by
      simulation, using the derived formulas. Based upon data from the Y-chromosomal
      Haplotype Reference Database (YHRD), the exclusion chance of a non-contributor is
      shown to vary between 95% in the case of two contributors, and 70% for five
      contributors. With only one additional contributor, half of all contributing
      suspects would yield a log-likelihood ratio in favour of donorship of 1.61 or
      higher, although the median drops to 0.66 with four additional contributors. It
      must be emphasised that these estimates of the discriminatory power of Y-STRs are
      likely to be conservative since the simulations involved only haplotypes known to
      occur in YHRD.

PMID- 15978348
TI  - Mass spectra and time-resolved fluorescence spectroscopy of the reaction product
      of glycine with 1,2-indanedione in methanol.
AB  - The reaction products of 1,2-indanedione (a new fluorescent fingerprint reagent)
      with glycine in methanol, at room temperature have been studied using excitation
      and emission and time-resolved fluorescence spectroscopy. Gas chromatography-mass
      spectroscopy (GC/MS) has also been used to determine which compounds are formed.
      Reaction products were identified using GC/MS as 2-carboxymethyliminoindanone
      (MW=203 g) and 1,2-di(carboxymethylimino)indane (MW=260 g). Identified compounds
      show room temperature fluorescence lifetimes of tau(1)=7.69 ns and tau(2)=1.27
      ns. It is not clear yet which compound is having fluorescence lifetime of 7.69 ns
      and which one is showing 1.27 ns.

PMID- 15978349
TI  - Survey of crowbar and household paints in burglary cases-population studies,
      transfer and interpretation.
AB  - Experimental data useful for the interpretation of paint evidence recovered
      during burglary cases were obtained. A population study was carried out on 41
      blue crowbars seized on suspects in Switzerland and 37 blue paints traces found
      at burglary scenes. Paint traces were also searched on the blades of 207 crowbars
      seized by the police in Switzerland and 24 white traces were analysed: these
      paints were analysed using infrared spectroscopy (FTIR) in order to estimate
      relative frequencies of each paint type. Simulated contacts were carried out
      between crowbars and painted wood in order to study the phenomenon of transfer
      and to evaluate the amount of paint transferred: a total of 198 simulations were
      carried out including individual, successive and cross transfer. The paint
      properties such as the chemical composition and its age influenced the amount of
      paint transferred. Cross transfer from the tool paint to the wood and vice versa
      was regularly observed. Moreover, secondary transfer of paint coming from the
      preceding wooden surfaces was also systematically observed: this could establish
      links between several burglary scenes and a suspected tool. A scenario of a
      burglary case involving the cross transfer between tool and household paints is
      proposed as a numerical example: the evaluation of such case was formalised using
      likelihood ratios based on the experimental data obtained.

PMID- 15978350
TI  - Qualitative and quantitative analysis of seized street drug samples and
      identification of source.
AB  - In this paper we describe the identification of constituents of the illicit drugs
      seized from different regions of eastern India by GC-MS. The constituents were
      identified to be heroin, acetyl morphine, morphine and acetyl codeine.
      Quantitative estimation of the constituents were made by GC-MS and HPTLC. In view
      of non-availability of the authentic samples of drugs of different origin,
      nothing positive can be said about the origin of illicit drug samples. The
      possibility of isotopic substitution, an important method for identification of
      source, was examined from the comparison of the intensity of different (ion)
      peaks 369 (heroin, m/z=369), 370, 371 and 372 using selective ion monitoring
      mode. No isotopic substitution in the constituents was observed. Attempts were
      made to identify the source of the illicit samples from heroin/acetylcodeine
      ratios in the way described in the literature.

PMID- 15978351
TI  - Raman spectroscopy of blue gel pen inks.
AB  - Raman spectroscopy is becoming a tool of major importance in forensic science. It
      is a non-invasive, non-destructive analytical method allowing samples to be
      examined without any preparation. This paper demonstrates the use of the
      technique as a general tool for gel pen inks analysis. For this purpose, 55 blue
      gel pen inks, of different brands and models representative of gel pen available
      on the world market at the time of this study, were collected. A preliminary
      solubility test in methanol allowed separating them into two classes: 19 dye
      based and 36 pigment-based gel inks. The latter were analysed by Raman
      spectroscopy (RS) using two wavelength laser sources (514.5 and 830 nm). Two main
      pigments were identified, pigment blue 15 and pigment violet 23.

PMID- 15978352
TI  - Fluorescence optimisation and lifetime studies of fingerprints treated with
      magnetic powders.
AB  - Fluorescence study plays a significant role in fingerprint detection when
      conventional chemical enhancement methods fail. The basic properties of
      fluorescence emission such as colour, intensity and lifetime could be well
      exploited in the detection of latent fingerprints under steady state and in
      dynamic methods. This paper describes a systematic study of fluorescence emission
      intensity from fingerprint samples treated with different magnetic powders.
      Understanding of suitable excitation wavelength required for getting maximum
      fluorescence emission intensity could be beneficial when selecting the
      appropriate fluorescent powders for the fingerprint detection. Lifetime study of
      fingerprints treated with various magnetic powders was also carried out. The
      importance of lifetime study is well explained through the time-resolved (TR)
      imaging of fingerprints with nanosecond resolution. Results from the TR imaging
      study revealed an improvement in the fingerprint image contrast. This is
      significant when the print is deposited on fluorescing background and its
      emission wavelength is close to that of treated fingerprint.

PMID- 15978354
TI  - Genetic profile of 15 STR loci in the Min Nan population in Southeast China.
AB  - Genetic profile of 15 short tandem repeats (STR) loci were determined in a
      Chinese Han population from the Min Nan mountainous area, Southeast China.

PMID- 15978353
TI  - Allelic frequencies of 13 STR loci in autochthonous Basques from the province of
      Vizcaya (Spain).
AB  - Allelic frequencies of 13 STR loci (D3S1358, VWA, FGA, D8S1179, D21S11, D18S51,
      D5S818, D13S317, D16S539, TH01, TPOX, CSF1PO, and D7S820) were estimated from a
      sample of 73 unrelated healthy donors natives of the Spanish Basque province of
      Vizcaya. These STR loci constitute the core of polymerase chain reaction (PCR)
      based DNA genetic markers in the US Combined DNA Index System (CODIS). All STR
      loci analysed met Hardy-Weinberg expectations. Based upon the allelic
      frequencies, forensically important parameters including gene diversity (GD),
      polymorphism information content (PIC) and power of discrimination (PD) were
      calculated.

PMID- 15978355
TI  - STR population diversity in nine ethnic populations living in Dubai.

PMID- 15978356
TI  - Allele frequencies of 19 STR loci in a Philippine population generated using
      AmpFlSTR multiplex and ALF singleplex systems.
AB  - Allele frequencies for the 19 short tandem repeat (STR) loci CSF1PO, D2S1338,
      D3S1358, D5S818, D7S820, D8S306, D8S1179, D13S317, D16S539, D18S51, D19S433,
      D21S11, DHFRP2 (FOLP23), F13A01, FES/FPS, FGA, TH01, TPOX, and vWA were obtained
      from a sample of 106 unrelated Filipinos from different regions of the Philippine
      archipelago.

PMID- 15978357
TI  - Genetic data for the 13 CODIS STR loci in Singapore Chinese.
AB  - Allele frequencies for the 13 CODIS STR loci included in the AmpFISTR Profiler
      Plus and AmpFISTR Cofiler kits (Applied Biosystems, Foster City, USA) were
      determined in a sample of 209 unrelated Chinese in Singapore. The combined random
      match probability for the 13 loci is about 6.6 x10(-15) and the overall
      probability of excluding paternity is 0.9999899. The results demonstrate that the
      loci are useful for forensic human identification and parentage testing for the
      Chinese population in Singapore.

PMID- 15978358
TI  - Y chromosome STR haplotypes in three UK populations.
AB  - Eleven Y chromosome short tandem repeat markers: DYS19, DYS385, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439, have been
      typed in the three main UK population groups: Caucasians, Afro-Caribbeans and
      South Asians. Existing PCR reactions were adapted to incorporate DYS437, DYS438
      and DYS439. The observed 11 loci haplotypes and the individual allele frequencies
      for each locus are presented. Distinct differences for most markers were observed
      between the population groups studied.

PMID- 15978359
TI  - Population data for the Identifier 15 STR loci in Hong Kong Chinese.
AB  - Allele frequencies for 15 STR loci, namely D8S1179, D21S11, D7S820, CSF1PO,
      D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and
      FGA, which are tested for by PE Applied Biosystem's Identifier kit, were obtained
      from a sample of 325 unrelated Chinese in Hong Kong.

PMID- 15978360
TI  - [Rapid diagnosis of outbreak-prone bacterial diseases].

PMID- 15978361
TI  - The impact of HCV diversity on diagnosis tools for HCV infection.

PMID- 15978362
TI  - [Chemical barriers for the prevention of HIV and sexually transmitted infections:
      overview on microbicide development].

PMID- 15978363
TI  - [Don't forget rabies!].

PMID- 15978364
TI  - [Leishmania transmission to children in Southern France].

PMID- 15978365
TI  - [Zoonoses in children from new pets].

PMID- 15978366
TI  - Antibiotic consumption in European hospitals.

PMID- 15978367
TI  - Antibiotic policies in European hospitals.

PMID- 15978368
TI  - Audits of antibiotic prescribing.

PMID- 15978369
TI  - Relationship between antibiotic consumption and resistance in European hospitals.

PMID- 15978370
TI  - [Microbiological pitfalls in the diagnostic of bone and joint infections].

PMID- 15978371
TI  - [Chronic carriage of hepatitis B virus and adoption].

PMID- 15978373
TI  - [Prospectives and issues of HPV vaccination in France].

PMID- 15978372
TI  - [A new town-hospital network for antibiotherapy: ANTIBIOLOR].

PMID- 15978375
TI  - [Hepatitis C virus infection and pregnancy].

PMID- 15978376
TI  - [Cytomegalovirus infection and pregnancy].

PMID- 15978377
TI  - [HIV risk and procreation, how to reduce HIV and HCV transmission risk for
      serodiscordant couples?].

PMID- 15978378
TI  - [<< Mortalite 2005 >> study in collaboration with Mortavic].

PMID- 15978379
TI  - [Epidemiology of discordant virologic and immunologic responses in HIV-1 infected
      patients].

PMID- 15978380
TI  - [An update on Interleukin-2 in HIV-infection].

PMID- 15978381
TI  - [Fluoroquinolone use and MRSA rates in hospitalized patients].

PMID- 15978382
TI  - [Community-acquired methicillin resistant Staphylococcus aureus].

PMID- 15978383
TI  - [Arthropods as epidemiological and diagnostic tools of emerging infectious
      diseases].

PMID- 15978384
TI  - [Septic shock and disorders of haemostasis].

PMID- 15978385
TI  - [Hypothalamic-pituitary-adrenal axis and septic shock].

PMID- 15978386
TI  - [Management of severe sepsis and septic shock in 2005--a practical approach].

PMID- 15978387
TI  - [Contribution of molecular diagnosis in clinical parasitology].

PMID- 15978388
TI  - [Do we need molecular biology for mycology in hospitals?].

PMID- 15978389
TI  - [Immunoproliferative small intestinal disease associated with Campylobacter
      jejuni].

PMID- 15978390
TI  - [What's new in dermatology and HIV infection in 2004].

PMID- 15978391
TI  - [Management of erysipela: an update].

PMID- 15978392
TI  - [Regulation of antibiotics in high and low respiratory pathologies supposed viral
      of the adult].

PMID- 15978393
TI  - [Severe dengue in Caribbean French departments as viewed by general practitioners
      (GPs)].

PMID- 15978394
TI  - [Are multiresistant micro-organisms present in GP'S offices?].

PMID- 15978395
TI  - [Visceral leishmaniases: epidemiology and diagnosis].

PMID- 15978396
TI  - [Therapeutic options for visceral leishmaniasis].

PMID- 15978398
TI  - [Methodology of study PAAIR II].

PMID- 15978397
TI  - [Are new antibiotics to be developed?].

PMID- 15978399
TI  - [A first turn of audit of practice on the topic of the antibiotic prescription in
      ORL and respiratory infections y 189 Lorraine general practitioners and
      pediatrists].

PMID- 15978400
TI  - [Care computer proceedings about probabilistic antibiotherapy in general
      practice].

PMID- 15978401
TI  - Implementing a clinical practice guideline on acute cough in general practice: a
      Belgian experience with academic detailing.

PMID- 15978404
TI  - Indications for amputations.
AB  - Amputation may take a psychological toll on a patient. Proper documentation is
      paramount along with a lucid informed consent. Various pathologies may lead to an
      amputation. Tools to aid in the decision to amputate, in choosing the levels of
      amputation, and in the selection of the type of procedure are available. The key
      to any amputation is to be at a level that is most definitive.

PMID- 15978405
TI  - Perioperative management of pedal amputations.
AB  - When performing a pedal amputation, proper preoperative, intraoperative, and
      postoperative care is essential for a successful outcome. This article outlines
      proper perioperative management for the amputation patient. All patients require
      appropriate medical management and testing before any surgical procedure;
      however, preoperative planning specific for the amputation patient also is
      required to determine the appropriate level of amputation and to provide an
      optimal result. The surgeon always must remember that patients with more distal
      amputations have a decreased energy expenditure and better functional outcome
      compared with their more proximal counterparts. Appropriate psychological
      counseling and physical rehabilitation also should be initiated as early as
      possible for the patient to recover fully in a timely fashion.

PMID- 15978406
TI  - Digital amputations.
AB  - Digital amputations may be indicated for trauma, tumor, transplantation,
      infection, peripheral vascular disease, congenital deformities, and chronic pain.
      This article reviews indications, general principles of amputation, surgical
      procedures, complications, postoperative course and rehabilitation, and clinical
      cases.

PMID- 15978407
TI  - Transmetatarsal amputations.
AB  - Transmetatarsal amputation is an excellent procedure in the face of nonhealing
      ulceration, infection, trauma, peripheral vascular disease, and tumors. This
      article discusses transmetatarsal amputations, the decision-making process,
      timing of surgery, operative techniques, postoperative management, and salvage of
      the failed transmetatarsal amputation.

PMID- 15978408
TI  - Lisfranc and Chopart amputations.
AB  - The issue of choosing an amputation level can be difficult for physicians. Every
      attempt should be made to maintain as much pedal length as possible to increase
      biomechanical function and ambulatory power. When there is excessive soft tissue
      loss because of trauma, infection, or vascular compromise, a Lisfranc amputation
      should be considered as a limb-salvage procedure. A more proximal midfoot
      amputation than Lisfranc is one at Chopart's articulation. This article addresses
      Lisfranc and Chopart amputations.

PMID- 15978409
TI  - Syme's amputation: a retrospective review of 10 cases.
AB  - Amputation at the level of the ankle joint is a valuable, yet underused procedure
      for a variety of conditions affecting the foot and ankle. The procedure can
      provide a comfortable and durable stump that allows a lower extremity amputee to
      function with minimal disability. The indications, surgical technique, and
      postoperative prosthetic considerations are reviewed and discussed. Emphasis is
      placed on the preoperative considerations deemed essential for a successful
      outcome based on the senior author's experience of 10 cases performed for a wide
      variety of pathologies. Three case illustrations show the efficacy of the Syme's
      procedure as an alternative to a higher level amputation, such as below-knee
      amputation or above-knee amputation.

PMID- 15978410
TI  - When is a more proximal amputation needed?
AB  - Amputation may be the most appropriate therapy for an ischemic or infected limb,
      but the level at which to amputate is often difficult to determine. Selecting the
      appropriate level is crucial when performing an amputation. The goals of surgery
      are to maintain maximal limb length and ensure successful healing. When more of
      the foot and limb can be preserved, the chances for rehabilitation are improved.
      This article reviews how to determine the most appropriate level of amputation.

PMID- 15978411
TI  - Tendon balancing in pedal amputations.
AB  - Pedal amputations are necessary procedures performed by a foot and ankle surgeon
      that may lead to gross positional deformities of the foot. To achieve a
      plantigrade foot, proper balancing of the foot is required often through the use
      of tendon transfers and lengthening. This article describes the basic tendon
      transfers needed to achieve a successful outcome when performing various pedal
      amputations. A case is presented in which Achilles tendon lengthening was used to
      heal a forefoot ulcer. A full understanding of tendon function and transfer
      techniques is paramount for surgeons performing pedal amputations. By rebalancing
      the foot, patients are able to ambulate with custom shoes or bracing, and more
      proximal amputations, which can be physically and psychologically devastating,
      are prevented.

PMID- 15978412
TI  - Complications of pedal amputations.
AB  - Partial foot amputations and revision and closure of such are some of the most
      challenging cases handled by all foot and ankle surgeons. Preoperative planning
      and perioperative decision making are tantamount to successful amputations of the
      foot. The goal of an amputation procedure is to achieve a definitive level at
      which the amputation will heal, and the foot will remain healed with no further
      breakdown for the life of the patient. This article discusses the reasons leading
      to complications status post partial amputation of the foot. Understanding these
      causes often minimizes a challenging course of healing, which all podiatric
      surgeons encounter after pedal amputations.

PMID- 15978413
TI  - Prosthetic management of the partial foot amputee.
AB  - Partial foot amputations provide advantages and challenges to the patient
      confronting loss of limb and the rehabilitation team. The partial foot amputation
      offers the potential for retention of plantar load-bearing tissues that are
      capable of tolerating the forces involved in weight bearing; this can allow the
      patient to ambulate with or without a prosthesis. Because of the complexity of
      the foot-ankle complex and the multiple types of partial foot amputations
      encountered, choosing the appropriate prosthesis can be challenging. This article
      explains some of the rationale and common options available for the different
      levels of amputation.

PMID- 15978414
TI  - Apoptosis coordinates with proliferation and differentiation during human hair
      follicle morphogenesis.
AB  - BACKGROUND: Apoptosis sculptures the most complicated skin appendage, feathers,
      out of epidermal layers by playing a variety of roles (1). Human hair follicle
      formation is different from feathers in growth direction and pattern formation of
      proliferative zone. OBJECTIVE: To delineate the apoptotic events together with
      proliferation and differentiation in developing human hair follicle and emphasis
      on the mechanism and biological meaning of epidermal hair canal. METHODS: We used
      TUNEL to examine apoptosis and Ki-67, involucrin, filaggrin immuno-localization
      to examine proliferation and differentiation. RESULTS: In hair germs, apoptosis
      was diffuse in periderm, basal keratinocytes, and mesenchymal cells with high Ki
      67 expression, but spared follicular germinative cells with low Ki-67 and high
      bcl-2 expression. In hair pegs, apoptosis was active in high Ki-67 expression
      area, like outer root sheath, hair follicle sheath, but spared dermal papilla
      with low Ki-67 and high bcl-2 expression. In bulbous pegs, apoptosis appeared in
      companion layer, precortical area, inner root sheath and outer root sheath, but
      spared bulge area with high bcl-2 expression. Apoptosis resulted in epidermal and
      subepidermal hair canal formation. Filaggrin and involucrin were expressed in the
      lining cells of hair canal. CD1a+ cells were densely distributed alone the hair
      canal before its opening. CONCLUSION: During human hair follicle morphogenesis,
      apoptosis coordinates with proliferation to shape the growth zone, creates space
      to free the hair shaft from follicular wall, and directs a driving force on hair
      shaft extension. Apoptosis accompanies the terminal differentiation of epidermal
      hair canal. The bottom becomes interfollicular epidermis after roof shedding and
      hair exposure. Langerhans cells also populate in the hair canal before its
      opening. The biological meaning of epidermal hair canal is supposed to prepare
      the barrier when hair perturbing the intact of epidermis.

PMID- 15978415
TI  - Inter-single-sequence-repeat-PCR typing as a new tool for identification of
      Microsporum canis strains.
AB  - BACKGROUND: Microsporum canis is a ubiquitous dermatophyte that commonly causes
      human infections. Since contact with infected animals is the usual way of
      infection, tracing its source is an essential preventive measure. OBJECTIVE: To
      type isolates of M. canis from human patients whose skin was affected, and from
      some animals (dogs and cats) that were closely associated to the patients.
      METHODS: The inter-single-sequence-repeat-PCR (ISSR-PCR) technique has been used
      for typing 24 isolates of M. canis. Seventeen isolates tested were from human
      patients, 5 from cats and 1 from a dog RESULTS: A total of 21 genotypes were
      identified. The same genotype was found infecting a patient and a cat that was
      living closely with him, but another member of the same family proved to be
      infected with two genotypes different from that. Clinical specimens from two
      patients had been contaminated with the same genotype, probably in the laboratory
      where the samples were handled. CONCLUSION: These results demonstrate that ISSR
      PCR polymorphism is a reliable method for the identification of the M. canis
      strains.

PMID- 15978416
TI  - Genetic identification and detection of human pathogenic Rhizopus species, a
      major mucormycosis agent, by multiplex PCR based on internal transcribed spacer
      region of rRNA gene.
AB  - BACKGROUND: Mucormycosis is an invasive opportunistic infection caused by fungi
      belonging to the order Mucorales. Due to the lack of laboratory tests, the
      diagnosis of mucormycosis is notoriously difficult. Added with its rapid
      progression as well as the debilitated state of the patients who contract the
      disease, mortality is extremely high. OBJECTIVE: The goal of this study was to
      genetically identify human pathogenic Rhizopus species, a major mucormycosis
      agent, by the internal transcribed spacer (ITS) region of rRNA gene. METHODS:
      Primers were designed to identify five Rhizopus species known to cause human
      disease by multiplex PCR. PCR was done not only with test strains and clinical
      isolates, but also with clinical samples from cutaneous mucormycosis patients.
      Sporangiospore morphology was observed by scanning electron microscopy to confirm
      the correlation of phenotypic and genotypic features. RESULTS: Multiplex PCR
      identified five Rhizopus species including Rhizopus oryzae, where R. azygosporus
      could only be distinguished from R. microsporus by certain polymorphisms that
      were present in its sequence. When this multiplex PCR was applied to clinical
      samples from three mucormycosis patients (paraffin sections from all and sera
      from one patient), Rhizopus DNA corresponding to the isolated pathogens were
      specifically detected. CONCLUSION: While fungal DNA detection from clinical
      samples is a rigorously studied area, this is the first report to genetically
      identify and detect Rhizopus species from human mucormycosis specimens. This may
      expand the possibility of this multiplex PCR system not only to identify isolated
      fungi, but also as a screening method for visceral mucormycosis.

PMID- 15978417
TI  - SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and
      keloid fibroblasts.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta induces fibroblast contraction,
      which is implicated in wound healing and keloid formation. SB-431542 is a novel
      specific inhibitor of TGF-beta type I receptor kinase activity. OBJECTIVE: We
      sought to determine whether SB-431542 inhibited TGF-beta-induced fibroblast
      contraction. METHODS: We used an in vitro type I collagen gel contraction assay
      with normal or keloid dermal fibroblasts incorporated. RESULTS: TGF-beta induced
      contraction of collagen gels with normal dermal fibroblasts incorporated, which
      was efficiently suppressed by SB-431542. Keloid fibroblasts showed higher basal
      contraction of collagen gels in the absence of TGF-beta than normal fibroblasts,
      which was enhanced by addition of TGF-beta. SB-431542 suppressed both the basal
      and TGF-beta-enhanced contraction of collagen gels by keloid fibroblasts. These
      inhibitory effects of SB-431542 were associated with suppression of TGF-beta
      induced alpha-smooth muscle actin (alpha-SMA) expression and phosphorylation of
      Smad2 in normal and keloid fibroblasts. CONCLUSION: SB-431542 can suppress TGF
      beta-induced contraction of collagen gel by normal and keloid dermal fibroblasts.
      Importantly, SB-431542 can inhibit basal contraction of collagen gel by keloid
      fibroblasts. These results suggest that an inhibitor of TGF-beta type I receptor
      kinase activity may have therapeutic potential for excessive skin contraction as
      observed in keloid.

PMID- 15978418
TI  - Microarray profiles of human basal cell carcinoma: insights into tumor growth and
      behavior.
AB  - PURPOSE: Basal cell carcinoma (BCC) is the most common human neoplasm. Much
      interest lies in determining the genetic basis of BCC to explain the unique
      locally invasive phenotype and infrequent metastatic behavior of these skin
      tumors. OBJECTIVE: We sought to examine a gene expression profile for BCC to
      elucidate new molecules responsible for its unique growth characteristics.
      METHODS: We analyzed gene expression patterns of 50 BCC tumors using spotted cDNA
      microarrays of 1718 characterized human genes related to cancer and immunity.
      This is the largest and most comprehensive gene expression study ever performed
      for BCC. Nodular and sclerosing histological subtypes of BCC were examined and
      compared to normal control skin. After statistical filtering, 374 significantly
      dysregulated genes were sorted by hierarchical clustering to determine trends of
      gene expression and similarities between patient gene expression profiles.
      RESULTS: A total of 165 upregulated genes and 115 downregulated genes were
      identified. These covered a range of categories, including extracellular matrix,
      cell junctions, motility, metastasis, oncogenes, tumor suppressors, DNA repair,
      cell cycle, immune regulation and angiogenesis. Clusters of genes were either
      commonly dysregulated across the 50 patient sample, or selectively affected in
      subsets of tumors. Histological subtypes were not distinguishable by hierarchical
      clustering. Many of the genes elucidated, including collagen type IV subunits and
      other novel candidates, possess functions related to extracellular matrix
      remodeling and metastasis. CONCLUSION: These results suggest a gene profile which
      may explain the invasive growth yet rarely metastatic behavior of BCC. The genes
      identified may also be potential targets for therapeutics aimed at further
      controlling invasiveness and local destruction of BCC.

PMID- 15978421
TI  - The evolution of radical cancer surgery.

PMID- 15978422
TI  - Radical surgery for cancer: a historical perspective.

PMID- 15978423
TI  - Evolution of lymphadenectomy in surgical oncology.

PMID- 15978424
TI  - Neck dissection: past, present, future.

PMID- 15978425
TI  - The evolution of surgery for breast cancer.

PMID- 15978426
TI  - Radical lobectomy, esophagectomy, and mediastinal dissections for intrathoracic
      malignancy.

PMID- 15978427
TI  - Radical gastrectomy and lymphadenectomy: historic overview, surgical trends, and
      lessons from the past.

PMID- 15978428
TI  - Pancreaticoduodenectomy (Whipple operation).

PMID- 15978429
TI  - Evolution of radical procedures for urologic cancer.

PMID- 15978430
TI  - Abdominoperineal resection for rectal cancer: historic perspective and current
      issues.

PMID- 15978431
TI  - Evolution of pelvic exenteration.

PMID- 15978432
TI  - Radical gynecologic surgery for cancer.

PMID- 15978433
TI  - Radical operations for soft tissue sarcomas.

PMID- 15978434
TI  - Transplanting allografts.

PMID- 15978435
TI  - The evaluation of casualties from Operation Iraqi Freedom on return to the
      continental United States from March to June 2003.
AB  - BACKGROUND: Most seriously wounded US Army casualties from the Iraqi theater of
      operations come through Walter Reed Army Medical Center on their return to the
      United States. General surgery and orthopaedic surgery services have developed a
      multidisciplinary team approach to triage and treatment of incoming casualties.
      STUDY DESIGN: Prospective database of returning casualties to Walter Reed Army
      Medical Center from Operation Iraqi Freedom (OIF) from March 1 to July 1, 2003.
      RESULTS: Of 294 casualties seen, 119 were triaged to inpatient status and treated
      within 1 hour of arrival; mean age 26.6 +/- 6.2 years (range 23 to 37). Time from
      original battlefield injury was a mean of 8 days (range 3 to 28 days). Forty-six
      (39%) sustained gunshot wounds, 37 (31%) sustained blast and shrapnel injuries,
      and 41 (34%) had blunt/motor vehicle collision mechanisms. There were a total of
      184 wounded locations in these 119 casualties; of these, there were 29 head and
      neck, 25 chest, 20 abdomen, 74 lower extremity, and 36 upper extremity. Twenty
      eight casualties (23%) required emergent surgical procedures on the night of
      arrival. Another 30 (25%) required an urgent surgical procedure within 48 hours
      of arrival. CONCLUSIONS: Followup surgical procedures were urgently or emergently
      required in 43% of admitted battlefield casualties from OIF on transfer to Level
      V care in the continental United States. The injury pattern of wounds from this
      engagement is described. The Walter Reed Army Medical Center system of incoming
      battlefield casualty evaluation using multidisciplinary teams is successful in
      expediting care and ensuring evaluation of the full range of potential injuries.

PMID- 15978438
TI  - Ultrasound-guided, vacuum-assisted, percutaneous excision of breast lesions: an
      accurate technique in the diagnosis of atypical ductal hyperplasia.
AB  - BACKGROUND: In October 2002, ultrasound-guided, vacuum-assisted, percutaneous
      excision was shown to facilitate the complete removal of benign breast lesions up
      to 3 cm in diameter. This study was performed to ascertain the overall accuracy
      of ultrasound-guided, vacuum-assisted, percutaneous excision as evidenced by the
      frequency of atypical ductal hyperplasia (ADH) underestimation. STUDY DESIGN: A
      retrospective review was conducted of 542 consecutive ultrasound-guided, vacuum
      assisted breast biopsies performed between February 2000 and September 2004.
      Before July 2002, no attempt was made to completely remove all imaged lesion
      evidence. After July 2002, all patients underwent complete percutaneous excision
      of all imaged lesion evidence. Pathology review revealed 52 lesions that
      demonstrated ADH and no evidence of malignancy. Each patient with this diagnosis
      was offered surgical excision. Pathologic reports for each group were compared
      with the subsequent open surgical specimens. RESULTS: Of 542 consecutively
      diagnosed lesions, 52 displayed ADH with no evidence of malignancy (10%). Five
      patients refused operation. Of the 47 patients who underwent open excision, 6
      (13%) were found to have malignancies. The rate of ADH underestimation was 6 of
      18 (33%) in incisional biopsies and 0 of 29 performed with complete imaged lesion
      evidence (p=0.002). The rate of ADH underestimation in women who underwent
      ultrasound-guided, vacuum-assisted, percutaneous excision was zero, a result
      equivalent to open surgical biopsy. CONCLUSIONS: ADH is a more common finding in
      sonographic lesions than has been previously reported. Complete ultrasound
      guided, vacuum-assisted, percutaneous excision is more accurate than
      nonexcisional ultrasound-guided biopsy. Patients so diagnosed have very low
      underestimation rates and may not require open surgical reexcision.

PMID- 15978439
TI  - Hand ischemia after radial artery cannulation.
AB  - BACKGROUND: Hand ischemia is a rare but potentially devastating complication of
      radial artery cannulation for arterial monitoring. The causes and ultimate
      outcomes of hand ischemia after radial artery cannulation are unclear. STUDY
      DESIGN: My colleagues and I reviewed the clinical course of radial cannula
      induced arterial thrombosis in eight patients during a recent 5-year period.
      RESULTS: Mean (+/- SD) duration of radial artery ischemia was 3 +/- 2 days.
      Injuries were associated with advanced (grade IIb) ischemia that affected the
      entire hand in four patients and first three digits in the other four patients.
      Radial artery thrombosis was documented using noninvasive tests or arteriography
      in all patients. Five injuries were initially treated with thrombectomy and patch
      angioplasty (n = 4) or vein graft interposition (n = 1); two others were treated
      nonoperatively with vasodilators, and one was observed without treatment. Three
      of the four patch angioplasty repairs occluded within 24 hours. Regardless of
      patency, all patients who survived arterial repairs had continuing ischemia that
      resulted in digital gangrene or amputation. In contrast, gangrene developed in
      only one patient treated nonoperatively. CONCLUSIONS: These data show that hand
      ischemia after radial artery cannulation is associated with high risk of tissue
      loss or amputation. Operative repair offered no advantage over nonoperative
      therapy in prevention of digital gangrene in this series. We hypothesize that
      digital gangrene results from distal embolization from the site of the initial
      arterial thrombosis, producing ischemia that is not remediated by radial artery
      revascularization. Nonoperative therapy with vasodilators can be equally
      effective in treating cannula-induced radial artery injuries in some patients.

PMID- 15978440
TI  - Simulator training for laparoscopic suturing using performance goals translates
      to the operating room.
AB  - BACKGROUND: The purpose of this study was to develop a performance-based
      laparoscopic suturing curriculum using simulators and to test the effectiveness
      (transferability) of the curriculum. STUDY DESIGN: Surgical residents (PGY1 to
      PGY5, n = 17) proficient in basic skills, but with minimal laparoscopic suturing
      experience, were enrolled in an IRB-approved, randomized controlled protocol.
      Subjects viewed an instructional video and were pretested on a live porcine
      laparoscopic Nissen fundoplication model by placing three gastrogastric sutures
      tied in an intracorporeal fashion. A blinded rater objectively scored each knot
      based on a previously published formula (600 minus completion time [sec] minus
      penalties for accuracy and knot integrity errors). Subjects were stratified
      according to pretest scores and randomized. The trained group practiced on a
      videotrainer suturing model until an expert-derived proficiency score (512) was
      achieved on 12 attempts. The control group received no training. Both the trained
      and control groups were posttested on the porcine Nissen model. RESULTS: For the
      training group, mean time to demonstrate simulator proficiency was 151 minutes
      (range 107 to 224 minutes) and mean number of attempts was 37 (range 24 to 51
      attempts). Both the trained and control groups demonstrated significant
      improvement in overall score from baseline. But the trained group performed
      significantly better than the control group at posttesting (389 +/- 70 versus 217
      +/- 140, p < 0.001), confirming curriculum effectiveness. CONCLUSIONS: These data
      suggest that training to a predetermined expert level on a videotrainer suture
      model provides trainees with skills that translate into improved operative
      performance. Such curricula should be further developed and implemented as a
      means of ensuring proficiency.

PMID- 15978441
TI  - Role of the small heat shock proteins in regulating vascular smooth muscle tone.
AB  - BACKGROUND: Vasospasm occurs in conduits used for vascular reconstructions. The
      small heat shock proteins, HSP20 and HSP27, coordinately regulate vascular smooth
      muscle tone. Phosphorylated HSP20 is associated with vasorelaxation, and
      phosphorylated HSP27 inhibits the phosphorylation of HSP20 and relaxation. We
      hypothesized that the relationship between the phosphorylated states of these two
      proteins might dictate the tone of a vessel and may contribute to vasospasm.
      STUDY DESIGN: Sodium nitroprusside relaxation of vascular smooth muscle was
      recorded using pig coronary artery and human saphenous vein. Segments were frozen
      and homogenized, and extracted proteins were separated by one- and two
      dimensional gel electrophoresis, transferred to Immobilon (Millipore), and probed
      with anti-cGMP-dependent protein kinase (anti-PKG), -HSP20, -HSP27, and 
      phosphoHSP27 antibodies. Band intensity was estimated using densitometry.
      RESULTS: Pig coronary artery completely relaxed (100%) with SNP (10(-7)M), but
      human saphenous vein only partially relaxed (20%). The levels of cGMP-dependent
      protein kinase and HSP20 were similar in the two tissue types. Human saphenous
      vein had significantly higher levels of HSP27 versus pig coronary artery (30.14
      +/- 0.8 versus 6.62 +/- 0.2 pixels/mg; p < or = 0.001) and phosphoHSP27 (8.29 +/-
      3.43 versus 0.012 +/- 0.008 pixels/mg; p < or = 0.001). CONCLUSIONS: Human
      saphenous vein contained significantly higher levels of HSP27 and pHSP27.
      Increased levels of phosphorylated HSP27 might contribute to vasospasm in human
      saphenous vein.

PMID- 15978442
TI  - Predictors of nonsentinel lymph node positivity in patients with a positive
      sentinel node for melanoma.
AB  - BACKGROUND: Patients found to harbor melanoma micrometastases in the sentinel
      lymph node (SLN) are recommended to proceed to complete lymph node dissection
      (CLND), although the majority of patients will have no additional disease
      identified in the nonsentinel lymph nodes (NSLNs). We sought to assess predictive
      factors associated with finding positive NSLNs, and identify a subset of patients
      with low likelihood of finding additional disease on CLND. STUDY DESIGN: We
      queried our prospective melanoma database for patients from January 1996 to
      August 2003 with a positive SLN. Univariable logistic regression models were fit
      for multiple factors and a positive NSLN. To derive a probabilistic model for
      occurrence of one or more positive NSLN(s), a multivariable logistic model was
      fit using a stepwise variable selection method. RESULTS: Of 980 patients who
      underwent SLN biopsy for cutaneous melanoma, 232 (24%) had a positive SLN; 221
      (23%) followed by CLND. Of these patients, 34 (15%) had one or more positive
      NSLN(s). In multivariable analysis, male gender (odds ratio [OR] 3.6 [95% CI
      1.33, 9.71]; p = 0.01), Breslow thickness (OR 4.58 [95% CI 1.28, 16.36]; p =
      0.019), extranodal extension (OR 3.2 [95% CI 1.0, 10.5]; p = 0.05), and three or
      more positive sentinel nodes (OR 65.81 [95% CI 5.2, 825.7]; p = 0.001) were all
      associated with the likelihood of finding additional positive nodes on CLND. Of
      47 patients with minimal tumor burden in the SLN, only 1 (2%) had additional
      disease in the NSLN. CONCLUSIONS: These results provide additional data to plan
      clinical trials to answer the question of who can safely avoid CLND after a
      positive SLN. Patients with minimal tumor burden in the SLN might be the most
      likely group, although defining "minimal tumor burden" must be standardized.
      Serial sectioning and immunohistochemistry on the NSLN in any "low-risk" group
      must be performed in a clinical trial to confirm that residual disease is
      unlikely before avoiding CLND can be recommended.

PMID- 15978443
TI  - Necrotizing enterocolitis associated with clostridium perfringens type A in
      previously healthy north american adults.
AB  - BACKGROUND: Necrotizing enteritis associated with Clostridium perfringens type C
      ("pigbel") is a well-known syndrome in severely protein-deprived populations in
      the Pacific. It is exceedingly rare in the developed world. C perfringens type A
      is a common cause of acute gastroenteritis and, in a handful of infections, has
      been reported in association with a syndrome resembling necrotizing enteritis.
      STUDY DESIGN: This study includes a case series and literature review. Charts and
      autopsy reports from four patients with adult necrotizing enterocolitis (ANEC)
      were reviewed. C perfringens isolates were subtyped by mouse bioassay and pulsed
      field gel electrophoresis. Fixed tissue specimens were tested with an
      anticlostridial antibody using an immunohistochemical assay. RESULTS: Between
      2000 and 2003, ANEC developed in four previously healthy men; three died. The
      small bowel was affected in three patients and the colon in two patients. Portal
      or mesenteric vein thrombosis occurred in three patients. C perfringens type A
      was isolated from three patients and immunohistochemical assay demonstrated
      clostridial antigens limited to affected areas of the intestine of all four. The
      nonculture positive patient had a strong epidemiologic link to one of the others,
      and a compatible clinical course. C perfringens of the same pulsed-field gel
      electrophoresis-defined molecular subtyped was isolated from stool samples of one
      patient, his wife, and food from a restaurant they patronized. CONCLUSIONS: ANEC
      associated with C perfringens type A infection occurred in four North American
      adults. Culture for C perfringens type A should be performed in cases of ANEC.
      Alternative tests such as immunohistochemical assay were diagnostically useful.
      Additional research might uncover virulence factors, host factors, and the burden
      of disease in the population.

PMID- 15978444
TI  - Technical complications and durability of hepatic artery infusion pumps for
      unresectable colorectal liver metastases: an institutional experience of 544
      consecutive cases.
AB  - BACKGROUND: Hepatic arterial infusion pump chemotherapy is an important component
      in the treatment of patients with hepatic metastases. Successful use of a hepatic
      arterial infusion pump requires a low technical complication rate. We evaluated
      the complications and longterm durability of these devices at our institution.
      STUDY DESIGN: Between April 1986 and March 2001, 544 patients underwent hepatic
      arterial infusion pump placement for treatment of unresectable colorectal liver
      metastases. Patient- and pump-related data were collected by chart review. Pump
      related complications, duration of pump function, and overall patient survival
      were recorded. RESULTS: Median patient survival was 24 months after pump
      placement. The incidences of pump failure were 9% at 1 year and 16% at 2 years.
      Pump complications occurred in 120 (22%) of the patients. Complications that
      occurred early after operation (< 30 days) were more likely to be salvaged than
      those occurring late (70% versus 30%, p < 0.001). Increased pump complication
      rates occurred in the setting of variant arterial anatomy (28% versus 19%, p =
      0.02), when the catheter was inserted into a vessel other than the gastroduodenal
      artery (42% versus 21%, p = 0.004), if the pump was placed during the first half
      of the study period (1986 to 1993, 25% versus 1994 to 2001, 18%; p = 0.05), and
      if the surgeon had performed fewer than 25 earlier procedures (< 25, 31% versus >
      or = 25, 19%; p < 0.002). CONCLUSIONS: In this large single institution
      experience, pump-related complications were low, the majority of early pump
      complications were salvaged, and pump complication rates improved as
      institutional experience accumulated. Longterm durability of pump function was
      excellent.

PMID- 15978445
TI  - Pyloromyotomy: a comparison of laparoscopic, circumumbilical, and right upper
      quadrant operative techniques.
AB  - BACKGROUND: Ramstedt pyloromyotomy through a right upper quadrant (RUQ)
      transverse incision has been the traditional treatment for hypertrophic pyloric
      stenosis. Recently, laparoscopic (LAP) and circumumbilical (UMB) approaches have
      been introduced as alternative methods to improve cosmesis, but concerns about
      greater operative times, costs, and complications remain. This study compares the
      three operative techniques and examines their advantages and complication rates.
      STUDY DESIGN: We performed a retrospective review of patients undergoing
      pyloromyotomy at a children's hospital between January 1997 and June 2003.
      RESULTS: Two hundred ninety patients underwent pyloromyotomy by LAP (n = 51), RUQ
      (n = 190), or UMB (n = 49). Complication rate, time to ad libitum feeding,
      incidence of emesis, and postoperative length of stay did not differ considerably
      among groups. Two LAP patients were converted to RUQ. Mucosal perforation
      occurred in three patients each in the RUQ and UMB groups, but none in the LAP
      group. Operative times were considerably less for LAP (25 +/- 9 minutes) than for
      RUQ (32 +/- 9 minutes) and UMB (42 +/- 12 minutes) (p < 0.05, ANOVA, Bonferroni).
      Charges related to operations and anesthesia were considerably greater for UMB
      (operation: US 1,574 dollars +/- US 433 dollars; anesthesia: US 731 dollars +/-
      US 190 dollars) compared with the other two groups (p < 0.05, ANOVA, Bonferroni),
      but did not differ between LAP (operation: US 1,299 dollars +/- US 311 dollars;
      anesthesia: US 586 dollars +/- US 137 dollars) and RUQ (operation: US 1,237
      dollars +/- US 411 dollars; anesthesia: US 578 dollars +/- US 167 dollars). Data
      are presented as mean +/- SD. CONCLUSIONS: Advantages of LAP include a shorter
      mean operative time without higher complications or costs. UMB is associated with
      the greatest mean operative time and costs. Laparoscopic pyloromyotomy is a safe
      and effective approach to the treatment of hypertrophic pyloric stenosis.

PMID- 15978446
TI  - Subxiphoid incisional hernias after median sternotomy.
AB  - BACKGROUND: Subxiphoid hernias are difficult to repair. This study attempts to
      identify risk factors associated with incisional hernia formation after median
      sternotomy. STUDY DESIGN: A retrospective review was conducted on patients
      undergoing subxiphoid incisional hernia repair between 1995 and 2002. The study
      group was compared with a group undergoing similar cardiothoracic procedures as
      to body mass index (BMI), comorbidities, complications, tobacco use, length of
      stay, ICU stay, bypass time, transfusion requirements, and wound infections.
      Statistical analysis utilized Student's t-test, chi-square, and Kaplan-Meier
      analysis. RESULTS: A total of 117 subxiphoid hernias were repaired; 45 were used
      for comparison with a matched cohort of 79 patients. Average time between
      sternotomy and hernia repair was 24.3 months (+/-16.8) with 22 (49%) patients
      developing hernias within 2 years. Mean followup was 48 months. The study group
      differed significantly from the nonhernia group in age (56.6 +/- 13.0 versus 62.2
      +/- 8.9, p = 0.01), mean length of stay (16.3 +/- 22.8 versus 10.2 +/- 6.7, p =
      0.03), BMI (29.6 +/- 4.5 versus 27.2 +/- 4.5, p = 0.01), number of
      transplantation patients (10 versus 1, p = 0.0003), and presence of sternal wound
      infection (18% versus 3.9%, p = 0.02). Multivariate analysis revealed
      significance in regard to transfusion requirements (p = 0.015) and approached
      statistical significance with BMI (p = 0.058). Of the 45 patients undergoing
      hernia repair, 31(69%) had a mesh repair and 10 (32%) patients recurred. Six
      (43%) patients without a mesh repair recurred. Seventy-five percent of the
      patients with sternal wound infections developed recurrent hernias. CONCLUSIONS:
      Transfusion requirements, BMI, and sternal wound infections might be associated
      with subxiphoid hernias after median sternotomy. Sternal wound infection
      increases the risk of recurrent incisional hernia.

PMID- 15978447
TI  - National variations in morbid obesity and bariatric surgery use.
AB  - BACKGROUND: Exploring bariatric surgery use provides data on effective treatment
      allocation. This study analyzed national rates of bariatric surgery use and the
      burden of morbid obesity by gender, census region, and age. STUDY DESIGN:
      Patients 18 years of age or older undergoing bariatric surgery were identified
      from the US 2002 Nationwide Inpatient Sample, and the national morbidly obese
      population 18 years of age or older was determined using the Centers for Disease
      Control and Prevention 2002 Behavioral Risk Factor Surveillance System databases.
      General population data were obtained from 2000 census data. Annual rates of
      bariatric surgery procedures were determined by gender, age group, and census
      region (Northeast, Midwest, South, and West). Rate ratios were calculated and
      significance tested through 95% confidence intervals (95% CI), accounting for the
      Nationwide Inpatient Sample and Behavioral Risk Factor Surveillance System
      sampling design. RESULTS: In 2002, a national cohort of 69,490 bariatric surgery
      patients was identified. Of these patients 85% were women and 76% were ages 18 to
      49 years. The prevalence of morbid obesity (body mass index > or = 40 kg/m(2)) in
      the US in 2002 was 1.8%; 60% of morbidly obese people were women, and 63% were
      ages 18 to 49 years. The rates of bariatric surgery procedures per 100,000
      morbidly obese individuals ranged from a low of 139 in men aged 60 years and
      older in the Midwest to a high of 5,156 in women ages 40 to 49 years in the
      Northeast. For both men and women, bariatric surgery rates in the West and
      Northeast were 1.35 (95% CI 1.31 to 1.40, p < 0.05) to 4.51 (95% CI 4.15 to 4.89,
      p < 0.05) times higher than in the South, respectively; rates in the Midwest were
      similar to those in the South. CONCLUSIONS: National estimates suggest that
      bariatric surgery rates do not parallel the burden of morbid obesity by region or
      age. Additional evaluation of these differences is necessary for optimal
      bariatric surgery use.

PMID- 15978448
TI  - Postoperative short bowel syndrome.
AB  - BACKGROUND: Unanticipated massive resection after intraabdominal procedures is an
      increasing cause of short bowel syndrome (SBS). Our aim was to determine the
      frequency and potential mechanisms of postoperative SBS. STUDY DESIGN: We
      reviewed retrospectively the clinical course of 210 adult patients with SBS
      evaluated over a 20-year period. RESULTS: Fifty-two (25%) patients had
      postoperative SBS. The initial operations included colectomy (n=20), hysterectomy
      (n=8), appendectomy (n=5), gastric bypass (n=5), and other (n=14). Intestinal
      obstruction (n=38) was the most common reason for resection leading to SBS,
      either from adhesions (n=26) or volvulus (n=12). Postoperative intestinal
      ischemia led to resection in 14 patients. SBS occurred from 1 day postoperatively
      to years later, with 16 (30%) intestinal resections occurring within 1 month.
      Patients undergoing resection for intestinal ischemia were more likely to undergo
      resection during the first month than were patients with adhesions and volvulus
      (86% versus 4% and 25%,respectively, p < 0.05): Patients undergoing resection for
      ischemia and volvulus were more likely to have remnant length<60 cm compared with
      those with adhesions (57% and 58% versus 23%, respectively, p < 0.05). Patients
      undergoing resection for adhesive obstruction were more likely to undergo
      multiple resections. Thirty-five (67%) patients required longterm parenteral
      nutrition. Seven (13%) patients died, three in the early postoperative period and
      four from complications of SBS. CONCLUSIONS: SBS is a potential postoperative
      complication of intraabdominal procedures and accounts for a considerable
      proportion of tertiary referrals for SBS. Surgical treatment of postoperative
      obstruction after common surgical procedures is the most frequent cause.
      Preventing adhesions, avoiding technical errors, diagnosing a potentially
      ischemic intestine in a timely manner, and approaching the frozen abdomen
      cautiously are important strategies for preventing this condition.

PMID- 15978449
TI  - What's new in general thoracic surgery.

PMID- 15978450
TI  - What's new in otolaryngology--head and neck surgery.

PMID- 15978451
TI  - The aviation paradigm and surgical education.

PMID- 15978452
TI  - Areola-sparing mastectomy: defining the risks.

PMID- 15978453
TI  - Alterations in gastrointestinal physiology after Roux-en-Y gastric bypass.

PMID- 15978454
TI  - Mechanisms of ventral hernia recurrence after mesh repair and a new proposed
      classification.

PMID- 15978455
TI  - Double trouble: duplication of vas deferens encountered during inguinal hernia
      repair.

PMID- 15978456
TI  - Pseudomembranous colitis.

PMID- 15978457
TI  - Surgical management of intraluminal duodenal diverticulum and coexisting
      anomalies.

PMID- 15978458
TI  - How cigarette smoke accelerates abdominal aortic aneurysm.

PMID- 15978459
TI  - Minimally invasive breast surgery.

PMID- 15978461
TI  - Liver resection using a saline-linked radiofrequency dissecting sealer for
      transection of the liver.

PMID- 15978463
TI  - Injury and pregnancy loss.

PMID- 15978464
TI  - Pain management after hernia repair.

PMID- 15978466
TI  - Septic complications after stapled hemorrhoidectomy.

PMID- 15978467
TI  - Anti-TNF alpha therapy and safety monitoring. Clinical tool guide elaborated by
      the Club Rhumatismes et Inflammations (CRI), section of the French Society of
      Rheumatology (Societe Francaise de Rhumatologie, SFR).

PMID- 15978485
TI  - Electrophysiological and speech perception measures of auditory processing in
      experienced adult cochlear implant users.
AB  - OBJECTIVE: This study determined the relationship between auditory evoked
      potential measures and speech perception in experienced adult cochlear implant
      (CI) users and compared the CI evoked potential results to those of a group of
      age- and sex-matched control subjects. METHODS: CI subjects all used the Nucleus
      CI-22 implant. Middle latency response (MLR), obligatory cortical potentials
      (CAEP), mismatch negativity (MMN) and P3a auditory evoked potentials were
      recorded. Speech perception was evaluated using word and sentence tests. RESULTS:
      Duration of deafness correlated with speech scores with poor scores reflecting
      greater years of deafness. Na amplitude correlated negatively with duration of
      deafness, with small amplitudes reflecting greater duration of deafness. Overall,
      N1 amplitude was smaller in CI than control subjects. Earlier P2 latencies were
      associated with shorter durations of deafness and higher speech scores. In
      general, MMN was absent or degraded in CI subjects with poor speech scores.
      CONCLUSIONS: Auditory evoked potentials are related to speech perception ability
      and provide objective evidence of central auditory processing differences across
      experienced CI users. SIGNIFICANCE: Since auditory evoked potentials relate to CI
      performance, they may be a useful tool for objectively evaluating the efficacy of
      speech processing strategies and/or auditory training approaches in both adults
      and children with cochlear implants.

PMID- 15978486
TI  - Face representation in the human secondary somatosensory cortex.
AB  - OBJECTIVE: To investigate the somatotopic organization of the facial skin area in
      the secondary somatosensory cortex (SII) in humans. METHODS: Somatosensory evoked
      magnetic fields following air-puff stimulation of 5 body sites, the foot, the lip
      and 3 points of the facial skin (forehead, cheek and mandibular angle point),
      were recorded. We focused on activities in SII following stimulation of these 5
      sites and compared dipole locations among them. RESULTS: There was a clear
      somatotopic organization in SII with lip in the most lateral area, foot in the
      most medial area and face in an intermediate area close to the lip area. However,
      there was no significant difference of dipole localization in SII among the 3
      areas of facial skin, similar to the overlapped somatotopic organization of
      facial skin areas in the primary somatosensory cortex in our previous study.
      CONCLUSIONS: The facial skin areas are considered to occupy a small area in SII
      with insufficient spatial separation to differentiate each area of facial skin
      even using magnetoencephalography which has a high spatial resolution.
      SIGNIFICANCE: This is the first systematic study of the activated regions in SII
      following stimulation of the facial skin.

PMID- 15978487
TI  - Lack of habituation of nociceptive evoked responses and pain sensitivity during
      migraine attack.
AB  - OBJECTIVE: The aim of the present study was to investigate the habituation of
      subjective pain sensation to CO(2) laser stimulus, in relation to the amplitude
      modifications of the cortical evoked responses (LEPs), during both the migraine
      attack and the not symptomatic phase. METHODS: Fourteen migraine patients were
      selected and compared with 10 healthy controls. Eight patients were evaluated
      during both the pain-free and the attack phases. Three following series of 20
      averaged LEPs were recorded, stimulating the hands and the supraorbital zones:
      during the attack, two consecutive series of 20 averaged LEPs were carried out.
      The subjective sensation was requested for each laser stimulus, using a 0-10
      points Verbal Rating Scale (VRS). RESULTS: In normal subjects the N2-P2 waves
      amplitude showed habituation across the three repetitions, which correlated with
      the habituation of the subjective rating of the stimulus. During the not
      symptomatic phase, patients showed a lack of habituation of the N2-P2 amplitude
      when the hand and the face was stimulated, with a pattern of increase of the pain
      rating across the three repetitions; in addition there was a lack of correlation
      between the LEPs amplitude and the subjective sensation. During the attack, the
      LEPs amplitude and the pain rating were increased when the face was stimulated,
      but they did not habituate across the two repetitions, likely the pain-free
      condition. The percent LEPs amplitude variation across the three repetitions
      correlated with the main indices of migraine severity, mainly when the
      supraorbital zone was stimulated. CONCLUSIONS: The abnormal cortical excitability
      in migraine could condition an anomalous behavior of nociceptive cortex during
      the interictal phase of migraine: it persists during the acute phase, and
      correlates with the frequency and duration of migraine. SIGNIFICANCE: The reduced
      habituation of the nociceptive cortex may concur with the onset and evolution of
      headache.

PMID- 15978488
TI  - Spectral analysis of sleep EEG in patients with restless legs syndrome.
AB  - OBJECTIVE: Conventional analyses of sleep EEG recordings according to standard
      criteria indicate severe sleep disturbances in patients with restless legs
      syndrome (RLS). Spectral analysis of sleep EEG may be a sensitive tool to detect
      functional alterations of sleep mechanisms beyond the visual scoring of
      polysomnographic records. We analysed sleep EEG spectral power differences
      between RLS patients and healthy subjects. Furthermore, we studied the
      relationship of sleep EEG spectral power to the occurrence of periodic leg
      movements in sleep (PLMS) and arousal events. METHODS: Sleep EEGs from 20
      patients with idiopathic RLS and of 20 age and sex matched healthy subjects were
      investigated. The spectral analysis was carried out on the same 30s epochs for
      which sleep stages had been determined. As a first step, whole-night spectral
      power excluding epochs with an arousal or with a PLMS was compared separately for
      REM and NREM sleep between RLS and healthy subjects. In a second step, we
      evaluated the spectral effects of PLMS, PLMS with associated arousals and
      isolated arousals relative to epochs of sleep without such events in both groups.
      In this part of the analysis, we only included the epochs of sleep stage 2 (the
      main and most stable non-REM sleep stage) and of REM sleep. RESULTS: Spectral
      power of all sleep epochs (excluding arousals and PLMS) did not differ between
      patients with RLS and healthy subjects. As expected, arousals and PLMS-associated
      arousals resulted in a significant increase in higher-frequency activity (alpha,
      beta1, beta2 and gamma bands) in both groups. Spectral power in epochs with PLMS
      alone did not significantly differ from spectral power in epochs without PLMS and
      without arousal in any of the groups. CONCLUSIONS: We found no evidence for an
      altered cortical activity in sleep stage 2 and REM sleep epochs in RLS patients
      compared to that in healthy controls if epochs with arousals were not considered.
      Furthermore, while PLMS associated with an arousal have a high impact on EEG
      spectra, the effect of a PLMS without arousal seems to be minor and transient.
      SIGNIFICANCE: Our data suggest that RLS related symptoms may intermittently
      disrupt sleep but do not appear to involve a persistent disturbance of the basic
      sleep generating patterns.

PMID- 15978489
TI  - Sympathetic and parasympathetic activities evaluated by heart-rate variability in
      head injury of various severities.
AB  - OBJECTIVE: To investigate the autonomic function in patients with brain damage of
      various extents. The purposes were to correlate the parameters derived from
      spectral analysis of the heart-rate variability (HRV) with the classic Glasgow
      coma scale (GCS), and to evaluate the possible clinical application of HRV in the
      autonomic functions in patients with various severities of brain-stem injury.
      METHODS: A total of 90 patients was divided into 5 groups based on the GCS: I:
      15, II: 9-14, III: 4-8, no pupil dilatation, IV: 4-8, pupil dilatation, and V: 3,
      brain death. Electrocardiogram was recorded for frequency-domain analysis of RR
      intervals. HRV were categorized into the low-frequency (LF, 0.04-0.15Hz) and high
      frequency power (HF, 0.15-0.40Hz), LF to HF power ratio (LF/HF), normalized
      powers (LF and HF%). These HRV parameters were correlated with the severity of
      brain damage. RESULTS: The LF, HF, LF%, and LF/HF in Group I were essentially
      similar to those in the normal subjects. LF and HF decreased from Group I to IV.
      All parameters were nearly absent in Group V. CONCLUSIONS: The increases in LF%
      and LF/HF with the decrease in HF indicate augmented sympathetic and attenuated
      parasympathetic drive. These changes were related to the severity of brain-stem
      damage. Both LF and HF were nearly abolished in brain death. SIGNIFICANCE: Our
      analysis indicates that HRV may be an useful tool for evaluating the autonomic
      functions in patients with brain damage of various degrees.

PMID- 15978490
TI  - Decreased vasoreactivity to right cerebral hemisphere pressure in migraine
      without aura: a near-infrared spectroscopy study.
AB  - OBJECTIVE: Several studies have reported changes in cerebrovascular reactivity
      during the interictal period of migraine. To characterize mechanisms of migraine,
      we compared changes in total haemoglobin (THbl) and regional oxygen saturation
      (rSO(2)) of the right and left frontal lobes in response to intracranial pressure
      changes during the interictal period of migraine. METHODS: Twelve right-handed
      migraineurs without aura and twelve age- and sex-matched healthy volunteers were
      asked to perform a head-down maneuver to increase intracranial venous pressure.
      Initial THbl was designated as 1.0, and all subsequent THbl measurements, which
      was proportional to the change in cerebral blood flow, were expressed as a value
      relative to this baseline. RESULTS: The head-down maneuver resulted in a
      significantly smaller increase in right-sided THbl in migraineurs when compared
      to volunteers (migraineurs, -0.1+/-0.04; volunteers, 30+/-13; P=0.027), but there
      was no significant difference in left-sided THbl when comparing migraineurs and
      volunteers. Further, the head-down maneuver produced a significantly smaller
      increase in right-sided THbl than in left-sided THbl in migraineurs (right side, 
      0.1+/-0.04; left side, 0.35+/-0.08; P<0.0001), but produced a significantly
      greater increase in right-sided THbl than in left-sided THbl in volunteers (right
      side, 30+/-13; left side, 0.44+/-0.13; P=0.030). The head-down maneuver resulted
      in a smaller decrease in right-sided rSO(2) in migraineurs when compared to
      volunteers (migraineurs, -4.1+/-2.2%; volunteers, -16+/-9.1%), but produced a
      significantly greater decrease in left-sided rSO(2) in migraineurs when compared
      to volunteers (migraineurs, -1.3+/-1.1%; volunteers, 2.8+/-0.63%; P=0.0037).
      CONCLUSIONS: These data indicate that pressure-related vasoreactivity is
      suppressed in the right hemisphere of migraineurs during the interictal period.
      SIGNIFICANCE: The suppression of vasoreactivity in the right hemisphere might be
      related to the pathogenesis of migraine.

PMID- 15978491
TI  - Head-down manoeuvre in patients with a high symptom score for orthostatic
      intolerance reveals impaired right brain frontal lobe vasoreactivity.
AB  - OBJECTIVE: Autonomic nerve dysregulation produces a sense of impaired well-being
      and interferes with work performance in affected individuals. In this study, we
      characterized the pathophysiology of this condition. METHODS: Six patients with
      high symptom scores for orthostatic intolerance (OI) along with age- and sex
      matched normal volunteers were directed to perform a head-down manoeuvre, and the
      change in cerebral blood flow (CBF) and cerebral oxygen levels (rSO(2)) in the
      right and left frontal lobes was measured using near-infrared spectroscopy
      (NIRS). RESULTS: The head-down manoeuvre induced a much greater increase in right
      sided total haemoglobin concentration (THbl) in normal volunteers (0.51+/-0.24)
      when compared to symptomatic patients (0.0+/-0.04) but had no effect on left
      sided THbl (P<0.05) in either group. Five of 6 patients showed a gradual decrease
      in right-sided THbl when assuming a sitting position, and all patients with this
      pattern complained of symptoms of multiple autonomic dysfunction. Further, this
      pattern of changes in right-sided THbl was not observed in normal volunteers.
      CONCLUSIONS: The gradual decrease of THbl with the sitting position and the lack
      of increase during the head-down manoeuvre in symptomatic patients suggest that
      these patients have impaired vasoreactivity in the right frontal lobes.
      SIGNIFICANCE: This impaired vasoreactivity likely reflects dysfunction of the
      right hemisphere and the sympathetic nervous system in patients with OI.

PMID- 15978492
TI  - Electric cortical stimulation suppresses epileptic and background activities in
      neocortical epilepsy and mesial temporal lobe epilepsy.
AB  - OBJECTIVE: To evaluate the suppressive effect of electric cortical stimulation
      upon the seizure onset zone and the non-epileptic cortex covered by subdural
      electrodes in patients with neocortical epilepsy and mesial temporal lobe
      epilepsy (MTLE). METHODS: Four patients with medically intractable focal epilepsy
      had implanted subdural electrodes for preoperative evaluation. Cortical
      functional mapping was performed by intermittently repeating bursts of electric
      stimulation, which consisted of 50 Hz alternating square pulse of 0.3 ms
      duration, 1-15 mA, within 5 s. The effect of this stimulation on the seizure
      onset zones and on the non-epileptic areas was evaluated by comparing spike
      frequency and electrocorticogram (ECoG) power spectra before and after
      stimulation. A similar comparison was performed in stimulation of 0.9 Hz of the
      seizure onset zones for 15 min. RESULTS: When the seizure onset zone was
      stimulated with high frequency, spike frequency decreased by 24.7%. Logarithmic
      ECoG power spectra recorded at stimulated electrode significantly decreased in 10
      32 Hz band by high frequency stimulation of the seizure onset zone, and in 14-32
      Hz band by high frequency stimulation of the non-epileptic area. Low frequency
      stimulation of the seizure onset zone produced 18.5% spike reduction and slight
      power decrease in 12-14 Hz. CONCLUSIONS: Both high and low frequency electric
      cortical stimulation of the seizure onset zone have a suppressive effect on
      epileptogenicity. Reduction of ECoG fast activities after electric cortical
      stimulation suggests the augmentation of inhibitory mechanisms in human cortex.

PMID- 15978493
TI  - Assessing interactions of linear and nonlinear neuronal sources using MEG
      beamformers: a proof of concept.
AB  - OBJECTIVE: This study aimed to explore methods of assessing interactions between
      neuronal sources using MEG beamformers. However, beamformer methodology is based
      on the assumption of no linear long-term source interdependencies [VanVeen BD,
      vanDrongelen W, Yuchtman M, Suzuki A. Localization of brain electrical activity
      via linearly constrained minimum variance spatial filtering. IEEE Trans Biomed
      Eng 1997;44:867-80; Robinson SE, Vrba J. Functional neuroimaging by synthetic
      aperture magnetometry (SAM). In: Recent advances in Biomagnetism. Sendai: Tohoku
      University Press; 1999. p. 302-5]. Although such long-term correlations are not
      efficient and should not be anticipated in a healthy brain [Friston KJ. The
      labile brain. I. Neuronal transients and nonlinear coupling. Philos Trans R Soc
      Lond B Biol Sci 2000;355:215-36], transient correlations seem to underlie
      functional cortical coordination [Singer W. Neuronal synchrony: a versatile code
      for the definition of relations? Neuron 1999;49-65; Rodriguez E, George N,
      Lachaux J, Martinerie J, Renault B, Varela F. Perception's shadow: long-distance
      synchronization of human brain activity. Nature 1999;397:430-3; Bressler SL,
      Kelso J. Cortical coordination dynamics and cognition. Trends Cogn Sci 2001;5:26
      36]. METHODS: Two periodic sources were simulated and the effects of transient
      source correlation on the spatial and temporal performance of the MEG beamformer
      were examined. Subsequently, the interdependencies of the reconstructed sources
      were investigated using coherence and phase synchronization analysis based on
      Mutual Information. Finally, two interacting nonlinear systems served as neuronal
      sources and their phase interdependencies were studied under realistic
      measurement conditions. RESULTS: Both the spatial and the temporal beamformer
      source reconstructions were accurate as long as the transient source correlation
      did not exceed 30-40 percent of the duration of beamformer analysis. In addition,
      the interdependencies of periodic sources were preserved by the beamformer and
      phase synchronization of interacting nonlinear sources could be detected.
      CONCLUSIONS: MEG beamformer methods in conjunction with analysis of source
      interdependencies could provide accurate spatial and temporal descriptions of
      interactions between linear and nonlinear neuronal sources. SIGNIFICANCE: The
      proposed methods can be used for the study of interactions between neuronal
      sources.

PMID- 15978494
TI  - Decomposing ERP time-frequency energy using PCA.
AB  - OBJECTIVE: Time-frequency transforms (TFTs) offer rich representations of event
      related potential (ERP) activity, and thus add complexity. Data reduction
      techniques for TFTs have been slow to develop beyond time analysis of detail
      functions from wavelet transforms. Cohen's class of TFTs based on the reduced
      interference distribution (RID) offer some benefits over wavelet TFTs, but do not
      offer the simplicity of detail functions from wavelet decomposition. The
      objective of the current approach is a data reduction method to extract succinct
      and meaningful events from both RID and wavelet TFTs. METHODS: A general energy
      based principal components analysis (PCA) approach to reducing TFTs is detailed.
      TFT surfaces are first restructured into vectors, recasting the data as a two
      dimensional matrix amenable to PCA. PCA decomposition is performed on the two
      dimensional matrix, and surfaces are then reconstructed. The PCA decomposition
      method is conducted with RID and Morlet wavelet TFTs, as well as with PCA for
      time and frequency domains separately. RESULTS: Three simulated datasets were
      decomposed. These included Gabor logons and chirped signals. All simulated events
      were appropriately extracted from the TFTs using both wavelet and RID TFTs.
      Varying levels of noise were then added to the simulated data, as well as a
      simulated condition difference. The PCA-TFT method, particularly when used with
      RID TFTs, appropriately extracted the components and detected condition
      differences for signals where time or frequency domain analysis alone failed.
      Response-locked ERP data from a reaction time experiment was also decomposed.
      Meaningful components representing distinct neurophysiological activity were
      extracted from the ERP TFT data, including the error-related negativity (ERN).
      CONCLUSIONS: Effective TFT data reduction was achieved. Activity that overlapped
      in time, frequency, and topography were effectively separated and extracted.
      Methodological issues involved in the application of PCA to TFTs are detailed,
      and directions for further development are discussed. SIGNIFICANCE: The reported
      decomposition method represents a natural but significant extension of PCA into
      the TFT domain from the time and frequency domains alone. Evaluation of many
      aspects of this extension could now be conducted, using the PCA-TFT decomposition
      as a basis.

PMID- 15978495
TI  - Cutaneous silent periods of the vastus medialis evoked by the stimulation of
      lateral femoral cutaneous nerve.
AB  - OBJECTIVE: Cutaneous silent period (CSP), which is a spinal reflex mediated by A
      delta cutaneous afferents, is transient suppression of the electromyographic
      activity. In this study, our aim is to investigate CSPs of vastus medialis muscle
      (vm-CSP) evoked by the stimulation of the lateral femoral cutaneous nerve (LFCN)
      in healthy controls and in patients with meralgia paresthetica (MP). METHODS:
      Twenty-one patients with MP (17 unilateral, 4 bilateral) and 27 healthy controls
      were included. Nerve conduction studies of LFCN and vm-CSP were analyzed in all
      subjects. A stimulus train consisting of five electrical shocks was applied to
      the skin at the anterolateral side of the thigh for recording of the vm-CSP.
      RESULTS: Nerve conduction abnormalities of LFCN were observed in all patients
      with MP. Mean duration of vm-CSP was 69.7+/-9.2ms, and mean onset latency was
      44.7+/-6.9 in healthy controls. Onset latency of vm-CSP was significantly
      prolonged and the duration of vm-CSP was significantly shortened in patients with
      MP. Vm-CSP abnormalities were observed in 20/25 extremities with MP. CONCLUSIONS:
      Dysfunction of A-delta afferents may cause these findings in patients with MP.
      Additionally, spinal modulation of pain may also play a role in the explanation
      of our findings. SIGNIFICANCE: The present study demonstrates the CSP alterations
      in the patients with entrapment neuropathy of a cutaneous nerve.

PMID- 15978496
TI  - Changes in the sympathetic skin response after thoracoscopic sympathectomy in
      patients with primary palmar hyperhidrosis.
AB  - OBJECTIVE: To investigate whether thoracic sympathectomy induced any change in
      the pattern of abnormalities or in the waveform of the sudomotor skin response
      (SSR) in patients with primary palmar hyperhidrosis (PPH). METHODS: We recorded
      the SSR to median nerve electrical stimuli before and after bilateral
      thoracoscopic sympathectomy in 27 patients with PPH. We analyzed the changes in
      amplitude, type of waveform and pattern of abnormality. RESULTS: All patients
      reported symptomatic improvement. The amplitude of the SSR decreased
      significantly in patients examined within 1 year after surgery, but was not
      different in patients examined after 1 year. The number of abnormally enhanced
      responses reduced after surgery, but there was no significant change in the
      number of patients with enhanced excitability recovery or with double-peak
      responses to single stimuli. There was a significant increase in the number of
      SSRs with a predominantly negative waveform after surgery. CONCLUSIONS: The
      persistence of SSR abnormalities after surgery suggests that the central nervous
      system dysfunction is not modified by sympathectomy. The change of the waveform
      to predominantly negative type after surgery could be the consequence of the
      decrease in the production of sweating. SIGNIFICANCE: Our results show the
      effects of sympathectomy on the SSR and on its abnormal patterns in patients with
      PPH.

PMID- 15978497
TI  - Shortening of distal motor latency in anode distal stimulation.
AB  - OBJECTIVE: Distal motor latency (DML) is shortened when the anode is held
      distally instead of the cathode by increasing the stimulus intensity. The
      objective of this study was to clarify the mechanism responsible for this
      shortening. METHODS: In seven healthy subjects, compound muscle action potential
      (CMAP) was obtained from the thenar muscle by bipolar stimulation of the median
      nerve at the wrist, and the intensity at which the first motor units were
      stimulated was defined as the threshold. Bipolar stimulation with extended
      interpole distance was employed to identify the generating site of the CMAP and F
      wave. RESULTS: The shortening of DML was dependent on the stimulus intensity and
      threshold. For the low threshold condition, the CMAP generating site was replaced
      from the proximal cathodal pole to the distal anodal pole by increasing the
      stimulus intensity. The generating site of the F-wave remained at the proximal
      cathodal pole irrespective of stimulus intensity. CONCLUSIONS: Replacement of the
      generating site results in the shortening of DML. When the F-wave is recorded
      after being induced by anode distal stimulation, CMAP should not be
      simultaneously evaluated. SIGNIFICANCE: This study clarified the generation sites
      of CMAP and the F-wave when induced by anode distal stimulation.

PMID- 15978498
TI  - Attenuation of the effect of remote muscle contraction on the soleus H-reflex
      during plantar flexion.
AB  - OBJECTIVE: We investigated to what extent the facilitation of the soleus (Sol)
      Hoffmann (H-) reflex during a phasic voluntary wrist flexion (Jendrassik
      maneuver, JM) can be modulated by graded plantar flexion force and conditioning
      wrist flexion force. METHODS: The subjects were asked to perform phasic wrist
      flexion under a reaction time condition. Sol H-reflex was evoked by stimulating
      the right tibial nerve at various time intervals (50-400ms) after the 'Go' signal
      for initiating JM while the ankle was at rest and while plantarflexing. The level
      of tonic plantar flexion force (isometric contraction of 10, 20 and 30% of
      maximal EMG) and conditioning wrist flexion (isometric contraction of 30, 50 and
      80% of maximum voluntary contraction) during JM was graded systematically.
      RESULTS: Although JM facilitation could be seen 80-120ms after the flexor carpi
      radialis (FCR) EMG onset even while plantarflexing, the magnitude of JM
      facilitation under plantar flexion was significantly decreased compared to that
      at rest. The degree of decrease in JM facilitation did not depend on the level of
      plantar flexion force. In contrast, the degree of JM facilitation was
      proportional to the level of wrist flexion force while the ankle was at rest and
      while plantarflexing, though the amount of JM facilitation significantly
      decreased while plantarflexing. CONCLUSIONS: JM facilitation of Sol H-reflex is
      decreased while performing tonic voluntary contraction of the homonymous muscle.
      The degree of decrease in JM facilitation is independent of the level of
      homonymous muscle contraction, but depends on the level of remote FCR
      contraction. In clinical application, when we intend to elicit a maximum stretch
      reflex by JM, full relaxation of homonymous muscle should be carefully confirmed.
      SIGNIFICANCE: Our results provide evidence for better understanding of the
      features of JM and insight into its clinical application.

PMID- 15978499
TI  - Reflex contribution of spindle group Ia and II afferent input to leg muscle
      spasticity as revealed by tendon vibration in hemiparesis.
AB  - OBJECTIVE: Foot dorsiflexion evokes a short- (SLR) and a medium-latency EMG
      response (MLR) in the soleus of standing subjects. SLR is mediated by spindle
      group Ia, while group II fibres contribute to MLR through an oligosynaptic
      circuit. We studied the effects of Achilles' tendon vibration on both responses
      in spastic patients to disclose any abnormal excitability of these pathways.
      METHODS: SLR and MLR were evoked in 11 hemiparetics and 11 normals. The vibration
      induced changes in both responses were correlated to the Ashworth score of the
      affected leg. RESULTS: There were no differences between normals and patients in
      the size of control SLR or MLR. Vibration decreased SLR to 70% in normal
      subjects, but increased it to 110% in patients, in both affected and unaffected
      leg. Vibration did not affect MLR in normals, but increased it to 165% on the
      affected and 120% on the unaffected side of patients. Ashworth score was solely
      correlated with the degree of vibration-induced increase of MLR. CONCLUSIONS:
      While the lack of inhibitory effect of vibration on SLR confirms a reduced
      inhibitibility of the monosynaptic reflex, the increased MLR indicates a
      disinhibition of group II pathway in patients, connected to the loss of
      descending control on group II interneurones. Spastic hypertonia depends on
      release of group II rather than group Ia reflex pathways. SIGNIFICANCE: These
      findings give a neurophysiological support for the pharmacological treatment of
      spastic hypertonia and suggest a method for the assessment of its effects.

PMID- 15978500
TI  - Synchronization of parietal and premotor areas during preparation and execution
      of praxis hand movements.
AB  - OBJECTIVE: We sought to determine temporal patterns of functional connectivity
      between the parietal, premotor, and motor cortices during preparation and
      execution of praxis hand movements. METHODS: Normal subjects were instructed to
      perform six transitive (tool use) and intransitive (communicative gesture) self
      paced pantomimes with the right hand while recording 64-channel
      electroencephalography (EEG) and electromyography (EMG) from right thumb and
      forearm flexors. Focusing on corticocortical coherence, we explored the time
      course of synchronously active parietal and premotor circuits involved in these
      motor tasks. Trials were marked for EMG onset and averaged across subjects to
      determine changes in coherence relative to baseline between parietal, premotor,
      and motor areas. RESULTS: Coherence of homologous electrode pairs was similar
      when comparing transitive and intransitive movements. During preparation, beta
      band (18-22 Hz) coherence was maximal between electrodes over the left parietal
      lobe and left premotor electrodes. Additionally during preparation, the premotor
      area showed high coherence to the motor hand area and the parietal cortex.
      Electrodes over the supplementary motor area also showed coherence to the motor
      and parietal, but not the premotor area. Before and during execution, a second
      peak of high coherence increase was present in each area that demonstrated
      coherence increases during preparation. There was no coherence increase between
      parietal and motor areas. Coherence rapidly diminished 1.5-2.0 s after movement
      onset. CONCLUSIONS: Patterns of increased corticocortical coupling within a
      parietal, premotor, and motor network are present during preparation and
      execution of praxis movements. SIGNIFICANCE: This study adds to evidence that
      parietofrontal networks may be critical for integrating preparatory and motor
      related activity for praxis movements.

PMID- 15978501
TI  - The impact of ventrolateral thalamotomy on high-frequency components of tremor.
AB  - OBJECTIVE: The present study assessed the impact of ventrolateral (VL)
      thalamotomy on the high-frequency components of tremor in patients with
      Parkinson's disease (PD). METHODS: Tremor was recorded prior to, and 7 days post
      surgery using a laser displacement sensor. In addition, tremor was recorded in 10
      age-matched patients with PD showing low amplitude tremor (named PD controls) and
      in 10 age-matched control subjects. Tremor recordings in patients were performed
      after a 12h withdrawal from anti-Parkinsonian drugs. Tremor characteristics such
      as amplitude, median power frequency (MPF) and power dispersion (a measure of
      concentration of power in the frequency domain) were assessed for all groups
      (i.e. controls, PD controls, pre-surgery and post-surgery). RESULTS: All tremor
      characteristics were similar between controls and PD controls. Tremor amplitude
      was significantly reduced post-surgery, to become statistically similar to that
      of controls and PD controls. However, MPF and power dispersion remained lower
      post-surgery, indicating that although there was normalization of tremor
      amplitude, tremor showed systematically slower oscillations after the surgical
      procedure. In order to eliminate amplitude as a possible confounding factor,
      epochs of post-surgical tremor (5s in duration) were paired for equal amplitude
      with 5s tremor epochs from matched controls. Results show once again that MPF and
      power dispersion were lower post-surgery compared to controls. In addition, when
      amplitude of power was compared within specific frequency bands (0-3.5, 3.5-7.5,
      7.5-12.5, 12.5-16.5, 16.5-30 and 30-45), power regained normal values at
      frequencies below 7.5 Hz. Power within higher frequency bands was systematically
      lower, indicating that the surgical procedure had an impact on high-frequency
      components of tremor. CONCLUSIONS: Results from the present study showed that VL
      thalamotomy reduced tremor amplitude by selectively targeting centrally driven
      components of PD tremor. The high-frequency component of physiological tremor
      failed to emerge after amplitude normalization. SIGNIFICANCE: The thalamus should
      then be considered as an important component of the generation and/or propagation
      of high-frequency components of physiological tremor.

PMID- 15978502
TI  - Reliability of the soleus H-reflex from supine to standing in young and elderly.
AB  - OBJECTIVE: Many recent studies have used the soleus H-reflex methodology to
      examine age-related changes in neuromuscular function. However, reliability of
      the method has only been tested in young adults. The purpose of this study was to
      evaluate the inter-trial reliability of the soleus H-reflex in both young and
      elderly subjects during supine and standing conditions. METHODS: The experiment
      was carried out on 10 young and 10 elderly subjects. For each subject, 10
      standardized soleus H-reflex trials were collected during each of the postural
      conditions. Intraclass correlations were calculated for the first 4, 6, 8, and 10
      trials for each group at each body position. RESULTS: The largest decreases in
      reliability in this study were observed with a decrease in the number of trials
      used to estimate the elderly soleus H-reflex during the standing condition. The
      change from using ten trials to using four trials led to an 8% decrease in
      reliability. CONCLUSIONS: Due to the decreased postural control ability in the
      elderly population, at least ten trials should be used to estimate soleus H
      reflex characteristics during standing or other functional weight-bearing
      conditions. SIGNIFICANCE: Using fewer than 10 trials could lead to an increase in
      statistical errors and misinterpretation of results.

PMID- 15978503
TI  - Preserved and impaired aspects of predictive grip force control in cerebellar
      patients.
AB  - OBJECTIVE: To analyze preserved and impaired aspects of feedforward grip force
      control during cyclic arm movements with a hand-held object after cerebellar
      damage. METHODS: We tested eight subjects with unilateral or bilateral cerebellar
      pathologies and eight healthy control subjects. Participants performed cyclic
      vertical arm movements with a hand held instrumented object at three different
      speeds. RESULTS: Compared to controls, patients excerted increased grip forces.
      The minimum force ratio between grip force and load force was constant across all
      movement frequencies, suggesting that patients anticipated speed-related changes
      in load magnitudes by adjusting the grip force. Thus the scaling of grip force
      level to self-generated load magnitudes was preserved. The coupling between grip
      and load profiles was assessed by cross correlation analysis. Patients exhibited
      significantly decreased maximum coefficients of cross correlation implicating
      impaired anticipation of inertial load fluctuations. However feedforward control
      could be preserved, as obvious from zero time lags of the maximum cross
      correlation coefficient. CONCLUSIONS: Our findings suggest that cerebellar
      lesions affect the processing of predictive grip force modulation in anticipation
      of inertial loads. Our results add further evidence to the theoretical concept
      that the cerebellum implements internal feedforward models. However, preserved
      functions may indicate compensatory mechanisms or extra-cerebellar aspects of
      grip and load force regulation. SIGNIFICANCE: The observed dissociation of
      performance deficits may have direct clinical implication and may guide the
      development of individual therapeutic strategies for patients with cerebellar
      disorders.

PMID- 15978504
TI  - Effects of masticatory muscle fatigue without and with experimental pain on jaw
      stretch reflexes in healthy men and women.
AB  - OBJECTIVE: To examine the effects of experimentally evoked masticatory muscle
      fatigue, without and with experimental muscle pain, on the short-latency jaw
      stretch reflex, using a randomised crossover design. METHODS: Reflexes were
      evoked in both the masseter and temporalis muscles in 15 men and 13 women. The
      study was performed in two blocks, both containing 3 experimental conditions
      (before, directly after, and 15 min after provocation). Provocation consisted of
      a fatiguing chewing test, followed by an intramuscular injection of either
      isotonic saline (IS; non-painful) or hypertonic saline (HS; painful). RESULTS: No
      significant effects of the experimental condition 'fatigue+IS' were found for any
      of the reflex outcome variables. For each muscle, the 'fatigue+HS' condition
      yielded significantly higher normalized reflex amplitudes than the other
      conditions. Several muscles displayed gender differences regarding both onset
      latency and normalized reflex amplitude. CONCLUSIONS: Experimentally evoked mild
      to-moderate muscle fatigue does not modulate the human jaw-stretch reflex. On the
      other hand, experimental muscle pain, evoked after the performance of a fatiguing
      chewing test, does yield a facilitation of this reflex. The gender differences
      found in both onset latency and peak-to-peak amplitude stress the need to take
      gender into consideration in future jaw reflex studies. SIGNIFICANCE: The
      sensitivity of the human jaw-stretch reflex can be modulated by HS-induced muscle
      pain; not by muscle fatigue that is provoked by intense chewing.

PMID- 15978505
TI  - Borderline personality disorder features in adolescent girls: P300 evidence of
      altered brain maturation.
AB  - OBJECTIVE: To examine brain maturation in adolescent girls with borderline
      personality disorder (BPD) features using the P300 event-related potential.
      METHODS: One hundred twenty-three girls, aged 14-19 yrs, were assigned to one of
      4 groups formed by the crossing of BPD features (vs. > or =5 BPD criteria) and
      median age (vs. >16.5 yrs). P300 responses were measured while subjects performed
      a complex visual oddball task. RESULTS: ANCOVAs of P300 amplitude-adjusting for
      variability associated with comorbid conduct disorder and depression symptoms-
      revealed a significant interaction. Among subjects without BPD features, aging
      was associated with the normal reduction in visual P300 amplitude. Among subjects
      with BPD features, there were no age-related changes. Additional analyses, which
      tested the effects of BPD features across the full age range, supported these
      findings. CONCLUSIONS: The present findings suggest abnormal brain maturation
      among adolescent girls exhibiting features of BPD. SIGNIFICANCE: These results
      support a hypothesis of altered brain maturation in adolescents exhibiting BPD
      features at an early age. It is suggested that measures of brain maturation
      obtained during adolescence may improve our ability to predict BPD and comorbid
      disorders in adulthood.

PMID- 15978506
TI  - Differential conditioning of alpha amplitude: a fresh look at an old phenomenon.
AB  - OBJECTIVE: To determine the latency and development of conditional suppression of
      alpha amplitude and its relationship to behaviour, alpha amplitude (8-13 Hz) was
      measured in a differential conditioning procedure. METHODS: The CS+/- were tones
      and the US was a photic checkerboard. Alpha amplitude, CNV, RT and verbal
      responses were recorded from 12 participants. RESULTS: The CS+/- difference in
      acquisition was greatest from 250 ms before the US. It was greatest from the
      trial where RT declined and participants could report the CS+/US relationship.
      There was an amplitude increase in lower band activity 230 ms after the US. This
      looked like a VEP but was produced by phase-locked activity starting before the
      US. CONCLUSIONS: Predicting the US led to cortical priming. Amplitude change in
      acquisition is congruent with CNV, RT and verbal performance. SIGNIFICANCE:
      Prediction, expectancy and motor preparation are reflected in changes in alpha
      activity. These results provide converging evidence for the functional role of 8
      10 Hz activity. They complement the emerging picture of the role of alpha
      activity in cognition, indicating that it extends to the acquisition of
      predictive knowledge.

PMID- 15978507
TI  - Neural mechanisms of global/local processing of bilateral visual inputs: an ERP
      study.
AB  - OBJECTIVE: Examine the neural mechanisms of global/local processing of multiple
      hierarchical stimuli. METHODS: Event-related brain potentials (ERPs) were
      recorded from adults who selectively attended to the global or local level of two
      compound letters that were simultaneously presented in the left and right visual
      fields, respectively. The compound stimuli were either broadband in spatial
      frequency (SF) spectrum or contrast balanced to remove low SFs. Subjects were
      asked to detect the presence of a global or local target that might appear in
      either the left or the right visual field in separate blocks of trials. RESULTS:
      Attention to the local level of broadband stimuli elicited a positivity over
      lateral occipital sites at 80-120 ms (P1) with larger amplitude than those in the
      global attention condition. However, global attention produced an enhanced
      positivity at 240-320 ms (P2) over lateral occipital sites relative to local
      attention. Both the P1 and P2 waves in the global condition were of larger
      amplitudes over the left than right hemispheres. Contrast balancing eliminated
      the P1 and P2 effects and modulated the hemispheric asymmetry of the long-latency
      occipital positivity. CONCLUSIONS: The results provide ERP evidence for
      modulations of neural activities in the visual cortex by global/local attention
      to concurrently presented multiple compound letters. Moreover, the modulation of
      brain activities by global/local attention depends upon the presence of low SFs
      in the compound stimuli. SIGNIFICANCE: The ERP results of this study contribute
      to the understanding of neural mechanisms of the processing of simultaneously
      presented multiple compound stimuli.

PMID- 15978508
TI  - Sex differences in adolescent ADHD: findings from concurrent EEG and EDA.
AB  - OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) occurs more frequently
      in male children and adolescents than in females, with a ratio of approximately 3
      to 1. We determined whether psychophysiological differences are associated with
      the expression of ADHD in males and females, using simultaneously recorded
      electroencephalography (EEG) and electrodermal activity (EDA). METHODS:
      Quantitative EEG and EDA measures were acquired simultaneously and continuously
      (2min) during an eyes closed resting condition for 70 ADHD adolescents (48 males,
      22 females) and their age- and sex-matched controls. RESULTS: Males and females
      with ADHD were differentiated by both EEG theta activity and EDA. ADHD males
      showed increased theta (widespread), whereas ADHD females showed a localised
      frontal enhancement of theta with reduced rate of EDA decrement. These sex
      differences were unrelated to ADHD subtype. CONCLUSIONS: These findings suggest
      that different psychophysiological processes may underlie ADHD in each sex. The
      profile of theta enhancement in ADHD males is consistent with a developmental
      deviation model of ADHD, whereas ADHD in females may be better understood within
      an arousal model, which emphasizes both central and autonomic function.
      SIGNIFICANCE: These findings highlight the potential for concurrent EDA measures
      to inform EEG studies of ADHD, particularly in regard to sex differences.

PMID- 15978509
TI  - Differences in behavioural phenotype between parental deletion and maternal
      uniparental disomy in Prader-Willi syndrome: an ERP study.
AB  - OBJECTIVE: Paternal deletion and maternal uniparental disomy are the principal
      genetic subtypes associated with Prader-Willi syndrome (PWS). Recent clinical
      findings suggest differences in phenotype between these subtypes. The present
      experimental study addresses this issue using a cognitive psycho-physiological
      setup. METHODS: Behaviour and event-related brain activity (ERP) was recorded by
      a continuous performance response inhibition task (CPT-AX) in adults with
      paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal
      controls (n=11). The dependent behavioural variables of the CPT-AX task were
      reaction time and correct scores. For the ERPs the N200 and P300 components were
      included which are related to early modality-specific inhibition and late general
      inhibition, respectively. RESULTS: The disomy group had fewer correct scores and
      increased reaction times as compared to the CPT-AX task than the control and
      deletion group. Both PWS subgroups differed significantly from the control group
      for the N200 amplitude. Only the control group showed the typical task modulation
      for the N200 amplitude. The amplitude of the P300 component was considerably
      smaller in the uniparental disomy group than in the deletion and control groups.
      CONCLUSIONS: The ERP results suggest that early modality specific inhibition is
      impaired in both PWS genetic subtypes. Late general inhibition is impaired in the
      uniparental disomy group only. Thus, although the ERP data suggests a common
      impairment in early visual inhibition processing, uniparental disomy and parental
      deletion genetic PWS subtypes clearly differ in their behavioural and brain
      activation phenotypes. SIGNIFICANCE: The present study is the first experimental
      demonstration which explains the two principal genetic mechanisms that hinder the
      expression of the genes at 15q11-q13g in PWS result in different behavioural
      phenotype.

PMID- 15978510
TI  - Effects of simulated high altitude on event-related potential (P300) and auditory
      brain-stem responses.
AB  - OBJECTIVE: This study investigated the effect of hyobaric hypoxia on cognitive
      function. METHODS: We recorded the auditory brain-stem response (ABR) and
      auditory-evoked event-related potentials (ERP) in 7 male subjects during a rapid
      ascent to a simulated 4500 m altitude from their acclimatized altitude of 610 m.
      The amplitude and latency of each component of ABR and of ERP were assessed.
      RESULTS: Compared with the values at 610 m, at 4500 m the latencies of both waves
      I and V of ABR significantly increased, with no change in I-V interpeak latency;
      and the amplitude of wave I decreased, with no change in the amplitude of wave V.
      The increase in altitude affected neither the amplitude nor the latency of N100.
      The P300 latency was prolonged significantly after exposure to hypobaric-hypoxic
      conditions for 2h, with no significant change in amplitude. At 4500 m, the P300
      latency returned to the baseline value after oxygen was inhaled. CONCLUSIONS: Our
      results suggest it is possible to boost cognitive processing by supplying oxygen
      even when auditory stimulus intensity decreases under hypobaric and hypoxic
      conditions, and that P300 latency is affected by hypoxic more than hypobaric
      conditions. SIGNIFICANCE: This study demonstrated that each component of ABR and
      the latency of both N100 and P300 are important to record when the effects of
      hypobaric hypoxia on cognitive function are investigated.

PMID- 15978511
TI  - Marked differences in the thermal characteristics of figure-of-eight shaped coils
      used for repetitive transcranial magnetic stimulation.
AB  - OBJECTIVE: To compare the heating behaviour of three figure-of-eight shaped coils
      during repetitive transcranial magnetic stimulation (rTMS). METHODS: A custom
      made coil (referred to as test coil) with a resistance-optimized conductor
      geometry was compared with two commercially available eight-shaped coils. Each
      coil was attached to the same energy source, which generated trains of 50
      biphasic magnetic pulses every 20s. Coil temperature was continuously measured
      during nine rTMS protocols using various combinations of stimulus frequencies (5,
      10 or 20Hz) and intensities (40, 50 or 60% of maximum stimulator output). A
      heating curve relating coil temperature and the number of applied stimuli was
      generated for each coil and rTMS condition. In eleven healthy volunteers, we
      evaluated the effectiveness of motor cortex stimulation. For each coil, we
      determined the motor threshold (MT) in the right first dorsal interosseus muscle.
      RESULTS: The slope of the heating curves of the test coil was markedly flattened
      relative to the heating curves of the two standard coils. This allowed the
      application of at least twice as many stimuli until the temperature of the coil
      reached 40 degrees C. Based on these data, we showed that a one-mass model could
      be used to accurately describe the heating behaviour of each coil. MTs determined
      with the test coil were comparable to or lower than the MTs that were determined
      with the standard coils. CONCLUSIONS: The efficacy of the test coil to stimulate
      the M1 was comparable to the efficacy of the two standard coils, yet thermal
      characteristics were markedly improved. SIGNIFICANCE: Overheating of figure-of
      eight shaped coils can be markedly delayed without reducing the efficacy of rTMS.

PMID- 15978512
TI  - Wrestling with restless legs.

PMID- 15978513
TI  - Management of sleep-disordered breathing in multiple system atrophy.

PMID- 15978514
TI  - Repeated IV doses of iron provides effective supplemental treatment of restless
      legs syndrome.
AB  - BACKGROUND AND PURPOSE: To evaluate in RLS patients the efficacy and safety of
      repeated infusions of iron in order to maintain symptomatic improvements achieved
      with a prior single 1000 mg infusion of iron. PATIENTS AND METHODS: Subjects who
      had demonstrated initial improvement in RLS symptoms after a single 1000 mg
      infusion of iron were evaluated monthly for serum ferritin and RLS severity. If
      symptoms returned at any time in the 2-year period after initial iron treatment,
      supplemental 450 mg iron gluconate infusions could be given, provided the
      ferritin was <300 mcg/l. The primary outcome measures were side effect profile,
      duration (weeks) of sustained improvement, and rate of change of serum ferritin.
      RESULTS: Ten subjects received the initial single 1000 mg dose of iron dextran,
      but only five subjects were eligible to receive supplemental iron infusions. RLS
      symptoms returned on average 6 months after the initial 1000 mg infusion. Because
      of noncompliance with monthly visits one subject was dropped after receiving
      three supplemental iron infusions. Because of a ferritin >300 mcg/l, a second
      subject was dropped after having received one supplemental treatment. Three
      subjects completed the 2-year period of the study, having received between two
      and four courses of supplemental iron. After the initial 1000 mg iron infusion,
      the ferritin declined on average 6.6 mcg/l/week, which was substantially higher
      than the predicted value of <1 mcg/l per week. The rate of ferritin decline
      decreased toward normal with repeated IV iron treatments: the average rate of
      decline in ferritin for the last treatment course was 2.3 mcg/l/wk. The slower
      the rate of ferritin decline the more prolonged the symptom improvements.
      CONCLUSIONS: Supplemental iron treatments can sustain previously achieved
      improvements with a single IV iron treatment, but achieving high ferritin levels
      was not in themselves a guarantee of sustained improvements. The most notable
      finding was the post-infusion changes in serum ferritin and its implication for
      altered iron excretion.

PMID- 15978515
TI  - Cultural influences on the bedtime behaviors of young children.
AB  - BACKGROUND AND PURPOSE: This study was designed to assess potential relationships
      of race and socioeconomic status (SES) to bedtime behavior from a community
      sample of 2- to 7-year-old children. PATIENTS AND METHODS: A previously validated
      sleep questionnaire was administered to parents of children enrolled in the
      Jefferson County, Kentucky school system. The sleep behavior of African-American
      (n=973) and Caucasian (n=2398) children was analyzed. Median annual income of
      residential zip codes was used as a proxy for SES. RESULTS: Mean age was 4.8+/
      1.1 years. Two composite 'sleep behavior scores' were generated related to
      excessive daytime sleepiness and sleep-related behavior. Children in the lower
      SES group had significantly more impaired 'sleep behavior scores' than those in
      the higher SES group, regardless of race or age. African-American children had
      later bedtimes than Caucasian children with similar rise times, resulting in
      significantly shorter sleep duration and more excessive daytime sleepiness,
      independent of SES and age. CONCLUSIONS: Cultural variables impact sleep-related
      behavior in children. Race and SES have independent relationships with sleep
      behavior. Independent of SES, African-American children sleep less due to later
      bedtimes. SES does play a role, however, in parentally reported sleep-related
      behavior problems. Thus, cultural variables such as race and SES are important
      modifiers of sleep behaviors in children and should be addressed in sleep
      education programs.

PMID- 15978516
TI  - Actigraphic recordings in quantification of periodic leg movements during sleep
      in children.
AB  - BACKGROUND: Periodic limb movement disorder (PLMD) has recently emerged as a
      relatively frequent and markedly underdiagnosed condition in children that
      induces arousals and sleep fragmentation and leads to poor learning and
      behavioral problems. Because a cost-effective and widely available alternative to
      pediatric polysomnography is needed for diagnosis of limb movement disorders,
      this study sought to examine whether periodic leg movements in children could be
      reliably identified using recently developed actigraphy software. METHODS:
      Bilateral actigraphs were worn around the feet by 99 children ages 4-12 years
      during standard clinical overnight polysomnography, which included bilateral
      anterior tibial electromyogram (EMG). Left and right leg movements were scored
      independently for comparison purposes. RESULTS: Agreement between tibial EMG and
      actigraphy-derived events were initially low, with movement indices being
      overestimated by actigraphy. This agreement was improved when a correction factor
      based on the average number of movements during arousals as measured by EMG was
      applied. However, the correction factor itself was found to differ substantially
      for patients who were diagnosed with PLMD compared to other patients.
      CONCLUSIONS: A novel actigraphic approach currently used for detection of PLM
      events during sleep in adults is insufficiently accurate to permit reliable
      estimates in children.

PMID- 15978517
TI  - Sleep disturbance in mild to moderate Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: To determine the prevalence of sleep disturbance in a
      memory clinic population of Alzheimer's disease (AD) patients and identify its
      clinical correlates. PATIENTS AND METHODS: Data from 215 attendees at a memory
      clinic, who were diagnosed with Alzheimer's disease, were examined. This included
      data from cognitive, functional and neuropsychological assessments. Sleep
      disturbance was determined using the question about diurnal rhythm disturbance on
      the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were
      compared. Group differences were analysed using univariate analysis and stepwise
      logistic regression analysis. RESULTS: The prevalence of sleep disturbance in
      this sample was 24.5%. The BEHAVE-AD 'aggressiveness' (P=0.009) and 'global
      rating' (P=0.029) (a measure of global impact of behavioural disturbance) were
      found to be significant predictors of sleep disturbance in AD. CONCLUSIONS: Sleep
      disturbance in AD is associated with other behavioural symptoms, notably
      aggressiveness. Sleep disturbance in AD has significant impact on the patient
      and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the
      clinician in choosing a suitable treatment for sleep disturbance in AD.

PMID- 15978518
TI  - Association between psychosocial job characteristics and insomnia: an
      investigation using two relevant job stress models--the demand-control-support
      (DCS) model and the effort-reward imbalance (ERI) model.
AB  - BACKGROUND AND PURPOSE: The details of risky psychosocial job characteristics
      related to insomnia are unclear, although potential relationships between the two
      have been suggested. The study objective was to clarify these relationships by
      using the demand-control-support (DCS) model and the effort-reward imbalance
      (ERI) model. PATIENTS AND METHODS: A cross-sectional questionnaire survey was
      conducted with 1081 middle-aged (39 years and older) workers in a corporate group
      of electric products in Osaka, Japan. The study variables included insomnia
      symptoms (non-refreshing sleep, difficulty falling asleep, frequent sleep
      disruption, and early morning arousal) and psychosocial job characteristics which
      were evaluated using the DCS and ERI models, gender, age, disease, sleep-related
      factors, occupational status, and health practices. RESULTS: ERI [odds ratio (95%
      confidence interval): 2.27 (1.43, 3.60)], overcommitment [1.86 (1.40, 2.47)], and
      high job strain [1.55 (1.12, 2.15)] were independently associated with insomnia.
      The odds ratio of insomnia for individuals with high job strain was increased by
      adding ERI or overcommitment. CONCLUSIONS: The ERI and DCS models describe the
      adverse psychosocial job characteristics related to insomnia. Simultaneously
      employing these two models is more useful than employing a single model to
      identify workers at risk of insomnia. The conceptual framework derived from the
      job stress models assists in defining preventive measures for insomnia in
      workers.

PMID- 15978519
TI  - Continuous positive airway pressure for sleep-related breathing disorders in
      multiple system atrophy: long-term acceptance.
AB  - BACKGROUND AND PURPOSE: To assess the long-term acceptance of non-invasive nasal
      continuous positive air pressure (CPAP) in multiple system atrophy (MSA) patients
      with polysomnographic (PSG)-confirmed sleep apneas and/or nocturnal stridor.
      PATIENTS AND METHODS: Sleep-related breathing disorders were investigated by PSG
      in 22 MSA patients in whom stridor and sleep-related respiratory disturbances
      were clinically suspected. Patients in whom the first PSG disclosed either a
      sleep apnea/hypopnea index (AHI)> or =10 or stridor with or without apneas
      underwent a second PSG for CPAP titration. RESULTS: Three patients presented with
      an obstructive sleep apnea syndrome without stridor, whereas 15 patients
      presented stridor occurring alone or accompanied by apneas. Twelve patients
      pursued CPAP. Two severely disabled patients died a few days after CPAP
      initiation, and five discontinued CPAP because of discomfort. One patient died
      after 17 months of follow-up. Since the onset of CPAP, the four remaining
      patients reported more efficacious sleep and improved daytime alertness. These
      patients had significantly less severe disease at the time of CPAP initiation.
      Age, disease duration, the presence of sleep complaints, excessive daytime
      somnolence (EDS) and AHI did not account for CPAP compliance. CONCLUSION: The
      severity of motor impairment at the initiation of treatment appears to be the
      most significant limiting factor for CPAP long-term acceptance.

PMID- 15978521
TI  - How do DCs interact with intestinal antigens?
AB  - Recent evidence demonstrates that dendritic cells (DCs) can insert dendrites
      between the epithelial cells that form the barrier protecting the body from the
      gut contents. Although first observed almost a decade ago, this is a
      controversial area of DC biology and the physiological importance of this
      phenomenon is only now being clarified. A recent study by Niess and colleagues
      shows that this behaviour enables efficient sampling of both invasive and non
      invasive bacteria and might enhance the ability of an organism to resist
      infections by a pathogenic strain of Salmonella.

PMID- 15978522
TI  - The bone marrow: a nest for migratory memory T cells.
AB  - It has been known for a long time that T-cell precursors generated in the bone
      marrow migrate to the thymus, where T-cell development occurs. However, a fact
      often neglected is that, under physiological conditions, mature CD4 and CD8
      lymphocytes undergo extensive migration from the blood to the bone marrow and
      vice versa. Here, we first review several observations showing that the bone
      marrow can function as a secondary lymphoid organ for both CD4 and CD8 cells, as
      well as a preferential homing site for memory T cells. Second, we discuss
      evidence that, a long time after priming, memory CD8 cells proliferate more
      extensively in the bone marrow than they do in either secondary lymphoid or extra
      lymphoid organs. Finally, we propose that the bone marrow is a central organ in
      mature T-cell traffic and contributes greatly to long-term cytotoxic memory,
      which has implications for adoptive immunotherapy and vaccine design.

PMID- 15978523
TI  - HMGB1: guiding immunity from within.
AB  - Two of the main challenges that eukaryotic multicellular organisms faced during
      evolution were to eliminate and replace dying cells and to cope with invading
      microorganisms. The innate immune system evolved to handle both tasks: to
      scavenge cellular debris and to form the first line of defence against microbes.
      In this review, we focus on high mobility group box 1 (HMGB1) protein as a common
      signal that alerts the innate immune system to excessive or deregulated cell
      death and to microbial invasion. HMGB1, which is well known nuclear protein, has
      revealed unexpected facets as an extracellular mediator. The role of HMGB1 as an
      endogenous molecule that facilitates immune responses and has an important role
      in tissue homeostasis and disease will be highlighted here.

PMID- 15978524
TI  - Non-tuberculous mycobacteria in HIV-infected patients: geographic, behavioural,
      and immunological factors.

PMID- 15978526
TI  - Panic pending over farming waste.

PMID- 15978527
TI  - When to initiate antiretroviral therapy in HIV-1-infected adults: a review for
      clinicians and patients.
AB  - One of the most controversial topics in the medical management of HIV disease is
      the optimal time to initiate highly active antiretroviral therapy (HAART) in HIV
      1-infected adults. Premature exposure to antiretrovirals may precipitate early
      evolution of resistance and unnecessary side-effects, whereas remaining off HAART
      until late in the course of HIV disease may lead to reduced therapeutic benefits
      and elevated mortality. The lack of a randomised clinical trial to consider this
      issue has resulted in ongoing revision of expert recommendations and substantial
      variability between international consensus guidelines regarding the optimal time
      to initiate therapy. Since this uncertainty is a source of unease for both
      patients and clinicians, we summarise the latest evidence regarding the optimal
      time to initiate HAART with consideration of the potential benefits and drawbacks
      of starting HIV treatment at the different levels presently recommended in
      leading consensus guidelines.

PMID- 15978528
TI  - Miliary tuberculosis: new insights into an old disease.
AB  - Miliary tuberculosis is a potentially lethal form of tuberculosis resulting from
      massive lymphohaematogeneous dissemination of Mycobacterium tuberculosis bacilli.
      The emergence of the HIV/AIDS pandemic and widespread use of immunosuppressive
      drugs has changed the epidemiology of miliary tuberculosis. Impaired cell
      mediated immunity underlies the disease's development. Clinical manifestations
      are non-specific and typical chest radiographic findings may not be seen until
      late in the course of the disease. Atypical presentations--eg, cryptic miliary
      tuberculosis and acute respiratory distress syndrome--often delay the diagnosis.
      Several laboratory abnormalities with prognostic and therapeutic implications
      have been described, including pulmonary function and gas exchange impairment.
      Isolation of M tuberculosis from sputum, body fluids, or biopsy specimens,
      application of molecular methods such as PCR, and histopathological examination
      of tissue biopsy specimens are useful for the confirmation of diagnosis. Although
      response to first-line antituberculosis drugs is good, evidence regarding optimum
      duration of treatment is lacking and the role of adjunctive corticosteroid
      treatment is unclear.

PMID- 15978529
TI  - Role of glycopeptides as part of initial empirical treatment of febrile
      neutropenic patients: a meta-analysis of randomised controlled trials.
AB  - We did a meta-analysis of randomised controlled trials studying glycopeptides as
      part of the initial empirical treatment of febrile neutropenic patients with a
      beta-lactam and with or without an aminoglycoside. 14 randomised controlled
      trials that studied 2413 patients were included in the analysis. A better outcome
      regarding treatment success, without modification of the initial regimen, was
      accomplished with the inclusion of a glycopeptide in the empirical therapy; this
      better outcome applied to the full set of studied patients (OR=1.63, 95% CI 1.17
      2.28), as well as in three important subsets of patients--those with
      microbiologically documented infections (2.03, 1.39-2.97), patients with
      bacteraemia (1.80, 1.23-2.63), and patients with severe neutropenia, defined as a
      white blood cell count below 100 cells/microL (2.24, 1.15-4.39). However,
      mortality was not different in the compared groups (0.67, 0.42-1.05). Overall
      treatment success was not different if a glycopeptide was added to the
      antimicrobial regimen in the case of continuation of fever 72 hours or more after
      the start of treatment (1.02, 0.68-1.52). Also, the inclusion of a glycopeptide
      in the empirical regimen did not lead to a difference regarding time to
      defervesence. Adverse effects (4.98, 2.91-8.55), including nephrotoxicity (2.10,
      1.12-3.95), were more common in the group receiving a glycopeptide as part of the
      empirical treatment. In conclusion, our meta-analysis suggests that there are
      good reasons why glycopeptides should not be routinely used as part of the
      initial empirical treatment of febrile neutropenic patients.

PMID- 15978530
TI  - Postgraduate training in infectious diseases: investigating the current status in
      the international community.
AB  - International collaboration and understanding is becoming increasingly important
      as we face a soaring number of emerging and re-emerging infectious diseases.
      Management of these conditions calls for a cohesive international effort, with
      contributions from many infectious disease specialists. To optimise collaborative
      efforts, an international understanding of training, capabilities, and skills
      would be valuable. An investigation of postgraduate training programmes in the
      infectious disease specialties around the world was done. 33 countries
      contributed information. 26 of these countries had established training
      programmes--one of which was changing its duration and research component; three
      were in the process of setting up programmes, two provided specialist training
      that had no official recognition, and two had no specialist training. In addition
      to promoting international understanding and collaboration, this article should
      catalyse a global assessment of postgraduate training programmes within the field
      of infectious diseases.

PMID- 15978531
TI  - Minimising antibiotic resistance.
AB  - The problems associated with antibiotic resistance have led to several agency and
      governmental reports since 1998, along with many sets of usage guidelines. These
      documents stress the desirability of reducing antimicrobial prescribing, which
      has subsequently fallen in several countries, including the UK. However, the
      evidence for any contingent reduction in resistance is scanty, and several
      pathogens--notably Escherichia coli--are becoming markedly more resistant. Thus,
      rather than being overly optimistic about the benefits of reducing antimicrobial
      prescriptions, we must also emphasise the use of those antibiotics that prove
      less prone to select resistance. Furthermore, we must be careful that guidelines
      are not so narrow as to rail-road prescribing and its contingent selection
      pressure in single directions--as happened with gonorrhoea--and to consider the
      likelihood that limited diverse prescribing may have the least detrimental effect
      upon the resistance ecology. Last, there is a need to re-invigorate antimicrobial
      development, which has been downgraded by many major pharmaceutical houses.

PMID- 15978532
TI  - Leg ulcer in a patient with agammaglobulinaemia.

PMID- 15978533
TI  - Harmonising the response to DSBs: a new string in the ATM bow.
AB  - Ataxia telangiestasia mutated protein (ATM) is the major kinase that initiates
      the DNA damage signal transduction response following exposure to ionising
      radiation (IR) in mammalian cells. DNA non-homologous end-joining (NHEJ) is the
      most significant double strand break (DSB) repair pathway in mammalian cells. ATM
      defective cell lines display cell cycle checkpoint defects and show pronounced
      radiosensitivity. ATM signalling was previously thought to be dispensable for
      NHEJ. This review discusses recent findings that ATM activates an end-processing
      mechanism dependent upon Artemis, a nuclease that also functions to cleave the
      hairpin intermediate generated during V(D)J recombination. ATM/Artemis-dependent
      end-processing is required for the repair of a sub-fraction (approximately 10%)
      of DSBs induced by IR and makes a significant contribution to survival following
      exposure to ionising radiation. This result represents a new role for ATM and
      demonstrates a novel cross communication between the DNA repair and signal
      transduction machinery.

PMID- 15978534
TI  - Immunisation in the current management of cystic fibrosis patients.
AB  - Although no special recommendations exist, clearly patients with cystic fibrosis
      (CF) can benefit from immunisation. We reviewed the literature regarding
      vaccination in CF and other chronic diseases. CF subjects should follow national
      immunisation programmes without delay to obtain optimal vaccination coverage.
      Indeed they may escape normal programmes due to frequent hospital admissions and
      school absenteeism and may be more at risk to get "vaccine-controlled" diseases
      at any age. There is no uniform European immunisation schedule for basic infant
      and childhood vaccines or for vaccines against hepatitis A (HAV) and B (HBV),
      varicella (VZ) and booster vaccinations. HAV and HBV vaccination is appropriate
      in CF as recommended in general for patients with chronic liver disease (CLD).
      Varicella (VZ) vaccination is not recommended in all European countries. There
      are no recent data about possible worsening of pulmonary status following VZ in
      CF, but it is known to cause pulmonary damage in non-CF adults and to be
      potentially fatal post transplantation and during steroid treatment. Therefore it
      is recommended at least for seronegative adolescents and transplant candidates.
      Influenza vaccine is recommended annually for CF patients aged > or =6 months.
      Pneumococcal vaccine is generally indicated for CF patients. RSV infection might
      play a role in the initial Pseudomonas colonization and the decline in pulmonary
      function. However no RSV vaccine is available at present. There are no
      recommendations for palivizumab in CF as an alternative but expensive
      prophylaxis. Anti-bacterial vaccinations protecting directly against Pseudomonas
      aeruginosa colonisation are promising for the future, potential candidates are
      currently being assessed in phase III clinical trials. More studies are needed to
      complete recommendations especially for CF adults and transplant candidates.

PMID- 15978536
TI  - Comparative analysis of Cystic Fibrosis Registry data from the UK with USA,
      France and Australasia.
AB  - BACKGROUND: Using the UK Cystic Fibrosis Database, we analysed the health of the
      UK CF paediatric population (UKPP) in terms of their biographical, clinical and
      infection status and compared outcomes with the US, French and Australasian CF
      Registries. METHODS: UKPP data were collected for 2,673 patients aged less than
      18 years in 2001 and used as a reference base for comparison with the most recent
      equivalent CF Registry reports. RESULTS: Although differences exist between
      National CF Registries, all record similar demographic factors and key outcomes.
      Where plausible comparisons can be made, we report that the UKPP had the oldest
      median age (15.0 years), the Australasian population had the lowest median age at
      diagnosis (1.8 months). Approximately, double the expected number of UKPP
      patients (23% and 19%, respectively) fall below the 10th centile for height and
      weight with similar outcomes in Australasia. UKPP and French populations had
      similar proportions with FEV1 >80% predicted (53% and 54%, respectively).
      CONCLUSION: Each Registry's data systems have developed independently providing a
      first step towards international comparisons. Standardisation of data collection
      criteria and definition for national CF Registries is required and we propose a
      standardised minimum data set, which would facilitate data integration as part of
      a global Registry for CF.

PMID- 15978535
TI  - Inhaled beta-agonists improve lung function but not maximal exercise capacity in
      cystic fibrosis.
AB  - BACKGROUND: To investigate the effects of inhaled beta-agonists on sub-maximal
      and maximal exercise capacity, breathing pattern, dyspnoea, leg-discomfort and
      spirometry in patients with cystic fibrosis (CF). OBJECTIVES: Eight patients
      performed two maximal incremental cycle-ergometry tests on separate days with
      inhaled placebo or salbutamol (600 microg) administered before each test in a
      randomized, double-blind, placebo-controlled crossover trial. Primary outcomes
      were exercise duration (Exdur) in seconds (s) and maximal oxygen uptake (VO2max)
      in litres/minute (L/min). Forced expiratory volume in 1 s (FEV1) was measured
      immediately pre-inhaler, post-inhaler and post-exercise. Dyspnoea and leg
      discomfort were assessed post-exercise. RESULTS: Within-day FEV1 comparisons
      demonstrated that the placebo test day FEV1 improved significantly post-exercise
      (0.11 L, p<0.05) and the salbutamol test day FEV1 improved significantly post
      inhaler (0.22 L, p<0.001) and post-exercise (0.07 L, p<0.01). Between-day FEV1
      comparisons demonstrated significant improvements in post-inhaler (0.17 L,
      p<0.05) and post-exercise (0.13 L, p<0.05) FEV1 following salbutamol. Sub-maximal
      and maximal exercise showed no significant difference as shown by Exdur (547+/
      154 s vs. 529+/-127 s) and VO2max (1.9+/-0.5 L/min vs. 1.9+/-0.6 L/min). No
      significant change in breathing pattern, dyspnoea or leg-discomfort was detected.
      The study had a power of 92% to detect a 10% improvement in Exdur. CONCLUSIONS:
      In adults with CF, salbutamol improves post-exercise FEV1 and is safe when
      administered immediately before exercise but does not improve exercise capacity,
      exercise-induced dyspnoea or leg-discomfort.

PMID- 15978537
TI  - Community physiotherapy for children with cystic fibrosis: a family satisfaction
      survey.
AB  - BACKGROUND AND PURPOSE: Input of a specialist physiotherapist is integral to the
      management of children with cystic fibrosis (CF). In recent years, many regional
      centres have developed specialist physiotherapy posts based in the community. The
      aim of this study was to ascertain the effectiveness of the community
      physiotherapy service in Newcastle upon Tyne, from the families' point of view.
      METHODS: The current service was reviewed and a questionnaire was developed and
      sent to all families with a child/children attending the regional paediatric
      centre for full care. It was adapted from a standardised patient satisfaction
      survey and included both open and closed questions. RESULTS: One hundred and six
      questionnaires were sent with a response rate of 50%. Eighty-nine percent of
      respondents had been reviewed by the community physiotherapist. Ninety-one
      percent were satisfied with the overall service provided. They felt involved in
      the treatment plan (94%) and understood the reasons for follow up visits (92%).
      Eighty-five percent of respondents had a contact number for the community
      physiotherapist. Comments from parents were generally positive. Many families
      requested increased input in the home as they found it more beneficial than
      review in the clinic setting. CONCLUSIONS: There was a high rate of satisfaction
      with specialist physiotherapy support in the community for children with CF among
      families who responded to the patient satisfaction survey.

PMID- 15978538
TI  - Clinical follow-up of 122 Italian cystic fibrosis patients with B. cepacia
      complex colonisation.

PMID- 15978539
TI  - Gas chromatography/mass spectrometry assay for arginine: glycine
      amidinotransferase deficiency.

PMID- 15978540
TI  - Kinetics properties of Cu,Zn-superoxide dismutase as a function of metal content.
AB  - The kinetics of bovine Cu,Zn superoxide dismutase were studied by pulse
      radiolysis. To ensure the absence of catalytically active free copper,
      commercially obtained holo-superoxide dismutase was demetallated, and the apo
      superoxide dismutase concentrations were determined by isothermal titration
      calorimetry prior to reconstitution with defined amounts of copper and zinc. The
      catalytic rate constant was determined as a function of ionic strength over the
      range of 4-154 mM, and of the copper and zinc content. The catalytic rate
      constant increases with ionic strength up to (1.5 +/- 0.2) x 10(9) M(-1) s(-1) at
      an ionic strength of 15 mM, and then decreases. At pH 7 and 50 mM ionic strength,
      k = (1.2 +/- 0.2) x 10(9) M(-1) s(-1), and at a physiologically relevant ionic
      strength of 150 mM, it is (0.7 +/- 0.1) x 10 (9) M(-1) s(-1). The effect of ionic
      strength is ascribed to the inhomogeneous electric field generated by the surface
      charges of superoxide dismutase. The value of the catalytic rate constant at 50
      mM is ca. 2-fold smaller than earlier values reported in the literature. The
      relationship between copper content and the catalytic rate constant shows that
      addition of more than a stoichiometric amount of copper cannot be masked
      efficiently by EDTA. The possibility exists that earlier reported values were
      based on experiments contaminated with trace amounts of copper.

PMID- 15978541
TI  - Mutational analysis of a monoterpene synthase reaction: altered catalysis through
      directed mutagenesis of (-)-pinene synthase from Abies grandis.
AB  - Two monoterpene synthases, (-)-pinene synthase and (-)-camphene synthase, from
      grand fir (Abies grandis) produce different product mixtures despite having
      highly homologous amino acid sequences and, presumably, very similar three
      dimensional structures. The major product of (-)-camphene synthase, (-)-camphene,
      and the major products of (-)-pinene synthase, (-)-alpha-pinene, and (-)-beta
      pinene, arise through distinct mechanistic variations of the electrophilic
      reaction cascade that is common to terpenoid synthases. Structural modeling
      followed by directed mutagenesis in (-)-pinene synthase was used to replace
      selected amino acid residues with the corresponding residues from (-)-camphene
      synthase in an effort to identify the amino acids responsible for the catalytic
      differences. This approach produced an enzyme in which more than half of the
      product was channeled through an alternative pathway. It was also shown that
      several (-)-pinene synthase to (-)-camphene synthase amino acid substitutions
      were necessary before catalysis was significantly altered. The data support a
      model in which the collective action of many key amino acids, located both in and
      distant from the active site pocket, regulate the course of the electrophilic
      reaction cascade.

PMID- 15978542
TI  - Interface mutation in heptameric co-chaperonin protein 10 destabilizes subunits
      but not interfaces.
AB  - We here report on a human mitochondrial co-chaperonin protein 10 (cpn10) variant
      in which the conserved interface residue leucine-96 is replaced with glycine
      (Leu96Gly cpn10). According to analytical ultracentrifugation, the mutation does
      not perturb the ability to assemble into a heptamer and electron microscopy
      reveals that Leu96Gly cpn10 is ring-shaped like wild-type cpn10. Despite
      elimination of a hydrophobic residue, the subunit-subunit affinity is essentially
      identical in Leu96Gly cpn10 and in wild-type cpn10. This is explained by a
      compensating rearrangement in Leu96Gly cpn10, evident from cross-linking and gel
      filtration experiments. As a direct result of lower monomer stability, Leu96Gly
      cpn10 is dramatically less stable towards chemical and thermal perturbations as
      compared to wild-type cpn10. We conclude that leucine-96 is an interface residue
      preserved to guarantee stable cpn10 monomers. Our study demonstrates that the
      cpn10 interfaces can adapt to structural alterations without loss of either
      subunit-subunit affinity or heptamer specificity.

PMID- 15978543
TI  - Schema therapy for patients with borderline personality disorder: a single case
      series.
AB  - The effectiveness of schema therapy for patients with borderline personality
      disorder (BPD) developed by Young was investigated using a single case series
      trial of six patients who all had primarily a DSM-IV BPD diagnosis. The treatment
      approach comprised the core elements of schema therapy with an emphasis on schema
      mode work and limited re-parenting. An A-B direct replication series with follow
      up assessments at 12 months was implemented. From baseline to follow-up
      improvement was large, as indicated by large effect sizes, and improvement was
      clinically meaningful for five of the six patients included. Three of the six
      patients did not any longer fulfill the criteria for BPD by the end of the
      treatment.

PMID- 15978544
TI  - The inactivation of bovine cathepsin B by novel N-chloro-acetyl-dipeptides:
      application of the Houghten 'tea bag' methodology to inhibitor synthesis.
AB  - In this study, a series of N-chloro-acetylated dipeptides were synthesised by the
      application of Houghten's methodology of multiple analog peptide syntheses
      (MAPS). The peptides, all of which contain a C-terminal free acid, were tested as
      inactivators of bovine cathepsin B, in an attempt at exploiting the known and,
      amongst the cysteine proteinases, unique carboxy dipeptidyl peptidase activity of
      the protease. We have succeeded in obtaining a number of effective inactivators,
      the most potent of which-chloroacetyl-Leu-Leu-OH, inactivates the enzyme with an
      apparent second-order rate constant of 3.8 x 10(4)M(-1)min(-1). In contrast, the
      esterified analog, chloroacetyl-Leu-Leu-OMe, inactivates the enzyme some three
      orders of magnitude less efficiently, lending credence to our thesis that a free
      carboxylic acid moiety is an important determinant for inhibitor effectiveness.
      This preliminary study has highlighted a number of interesting features about the
      specificity requirements of the bovine proteinase and we believe that our
      approach has great potential for the rapid delineation of the subsite
      specificities of cathepsin B-like proteases from various species.

PMID- 15978545
TI  - Single particle detection and characterization of synuclein co-aggregation.
AB  - Protein aggregation is the key event in a number of human diseases such as
      Alzheimer's and Parkinson's disease. We present a general method to quantify and
      characterize protein aggregates by dual-colour scanning for intensely fluorescent
      targets (SIFT). In addition to high sensitivity, this approach offers a unique
      opportunity to study co-aggregation processes. As the ratio of two fluorescently
      labelled components can be analysed for each aggregate separately in a
      homogeneous assay, the molecular composition of aggregates can be studied even in
      samples containing a mixture of different types of aggregates. Using this method,
      we could show that wild-type alpha-synuclein forms co-aggregates with a mutant
      variant found in familial Parkinson's disease. Moreover, we found a striking
      increase in aggregate formation at non-equimolar mixing ratios, which may have
      important therapeutic implications, as lowering the relative amount of aberrant
      protein may cause an increase of protein aggregation leading to adverse effects.

PMID- 15978546
TI  - Differential degradation of variant medium-chain acyl-CoA dehydrogenase by the
      protein quality control proteases Lon and ClpXP.
AB  - The coordinated activities of chaperones and proteases that supervise protein
      folding and degradation are important factors for deciding the fate of proteins
      whose folding is impaired by missense variations. We have studied the role of Lon
      and ClpXP proteases in handling of wild-type and a folding-impaired disease
      associated variant (R28C) of the mitochondrial enzyme medium-chain acyl-CoA
      dehydrogenase (MCAD). Using an Escherichia coli model system, we co-overexpressed
      the MCAD variants and the respective proteases at two conditions: at 31 degrees C
      where R28C MCAD protein folds partially and at 37 degrees C where it misfolds and
      aggregates. Co-overexpression of Lon protease considerably accelerated the
      degradation rate of a pool of R28C variant MCAD synthesised during a 30min pulse
      and counteracted accumulation of aggregates at 37 degrees C, whereas increasing
      the amounts of ClpXP protease had no clear effect. Co-overexpression of either
      Lon or ClpXP protease markedly decreased the steady state levels of both wild
      type and R28C mutant MCAD at 37 degrees C but not at 31 degrees C. Our results
      suggest that Lon is more efficient than ClpXP in elimination of non-native MCAD
      protein conformations, and accordingly, that Lon can recognise a broader spectrum
      of MCAD protein conformations.

PMID- 15978547
TI  - Prostaglandin E2 induces the expression of functional inhibitory CD94/NKG2A
      receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I
      pathway.
AB  - The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits
      cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is
      expressed by NK cells and by a small fraction of activated T cells, predominantly
      of CD8+ phenotype. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on
      cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance
      in cancer or HIV infection. In an attempt to identify the mechanisms leading to
      inhibitory NKR upregulation on T cells, we analyzed the expression of the
      CD94/NKG2A heterodimer on human CTLs activated with anti-CD3 mAb in the presence
      of PGE2 or with 8-CPT-cAMP, an analogue of cyclic AMP. As previously described,
      anti-CD3 mAb-mediated activation induced the expression of CD94/NKG2A on a small
      fraction of CD8+ T cells. Interestingly, when low concentrations of PGE2 or 8-CPT
      cAMP were present during the culture, the proportion of CD8+ T cells expressing
      CD94/NKG2A was two- to five-fold higher. This upregulation was partially
      prevented by PKA inhibitors, such as KT5720 and Rp-8-Br-cAMP (type I selective).
      We also report that cAMP induces upregulation of NKG2A at the mRNA level. We
      further demonstrated that cross-linking of CD94 on CD8+ T cells expressing the
      CD94/NKG2A heterodimer inhibits their cytotoxic activity in a bispecific antibody
      redirected lysis assay. Our findings clearly demonstrate that the PGE2/cAMP/PKA
      type I axis is involved in the expression of CD94/NKG2A receptor on human CD8+ T
      lymphocytes.

PMID- 15978548
TI  - Motor flexibility problems as a marker for genetic susceptibility to attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Since many children with attention-deficit/hyperactivity disorder
      (ADHD) have fine visuomotor problems that are already evident at a young age,
      motor dysfunctioning is investigated in family-genetic perspective. We
      hypothesized that if fine motor problems may be a marker for genetic
      susceptibility to ADHD, nonaffected siblings of ADHD probands would experience
      motor problems similar to those of their ADHD siblings. METHODS: Twenty-five
      carefully phenotyped ADHD probands with a family history of ADHD, their
      nonaffected siblings (n = 25), and 48 normal control subjects (aged 6 to 17)
      completed a motor fluency task and a motor flexibility task. The motor fluency
      task involved completion of a familiar, automatized trajectory, whereas the motor
      flexibility task required continuous adjustment of movement to complete an
      unpredictable random trajectory. RESULTS: On the motor fluency task, the
      performance of the nonaffected children was significantly better than that of the
      ADHD probands; strikingly, on the motor flexibility task, they performed as well
      as their ADHD siblings. CONCLUSIONS: Nonaffected siblings experience complex
      motor problems similar to their ADHD siblings but only in nonautomatized
      movements that require controlled processing. The results suggest that higher
      order controlled motor deficits in ADHD may be associated with genetic
      susceptibility for ADHD.

PMID- 15978549
TI  - Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel
      based morphometry study.
AB  - BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have
      investigated the presence of brain abnormalities in obsessive-compulsive disorder
      (OCD) but have not produced consistent findings. This might be partly related to
      their use of a regions-of-interest approach. We assessed gray matter volumes in
      19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM).
      METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and
      segmented with optimized VBM. Statistical comparisons were performed with the
      general linear model. RESULTS: Significant findings were detected in regions
      predicted a priori to be implicated in OCD, including increased gray matter in
      OCD subjects relative to control subjects in posterior orbitofrontal and
      parahippocampal regions; decreased gray matter in OCD patients in the left
      anterior cingulate cortex; and inverse correlations between obsessive-compulsive
      symptom severity and gray matter in the medial thalamus (p < .001, uncorrected
      for multiple comparisons). Also, an unpredicted site of gray matter reduction in
      OCD patients in the right parietal associative cortex approached significance (p
      = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are
      consistent with previous studies implicating dysfunction of orbitofrontal,
      cingulate, thalamic, and temporolimbic regions in OCD and suggest that the
      involvement of the parietal cortex in the pathophysiology of OCD warrants further
      investigation.

PMID- 15978551
TI  - Unsupervised fuzzy clustering analysis supports behavioral cutoff criteria in an
      animal model of posttraumatic stress disorder.
AB  - BACKGROUND: Unsupervised fuzzy clustering (UFC) analysis is a mathematical
      technique that groups together objects in the multidimensional feature space
      according to a specified similarity measurement, thereby yielding clusters of
      similar data points that can be represented by a set of prototypes or centroids.
      METHODS: Since clinical studies of mental disorders distinguish between affected
      and unaffected individuals, we designed an inclusion/exclusion criteria (cutoff
      behavioral criteria [CBC]) approach for animal behavioral studies. The effect of
      classifying the study population into clearly affected versus clearly unaffected
      individuals according to behaviors on two behavioral paradigms was statistically
      significant. RESULTS: Here the raw data from previous studies were subjected to
      UFC algorithms as a means of objectively testing the validity of the concept of
      the CBC for our experimental model. The first UFC algorithm yielded two clearly
      discrete clusters, found to consist almost exclusively of the exposed animals in
      the one and unexposed animals in the other. The second algorithm yielded three
      clusters corresponding to animals designated as clearly affected, partially
      affected, and clearly unaffected. The algorithm for physiological data in
      addition to behavioral data failed to elicit discrete clusters. CONCLUSIONS: The
      UFC analysis yielded data that support the conceptual contention of the CBC and
      lends additional validity to our previous behavioral studies.

PMID- 15978550
TI  - Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion
      tensor imaging study.
AB  - BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported
      abnormalities in two critical white matter tracts in schizophrenia, the uncinate
      fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal
      connectivity. Here, we investigate these two bundles in unmedicated subjects with
      schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15
      male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA)
      and mean diffusivity (D(m)) were used to quantify water diffusion, and cross
      sectional area was defined with a directional threshold method. Exploratory
      correlation analyses were evaluated with Spearman's rho, followed by post hoc
      hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the
      UF of SPD subjects. For CB, there was no significant group difference for FA or
      D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated
      with clinical symptoms, including ideas of reference, suspiciousness, restricted
      affect, and social anxiety. In contrast, left UF area was correlated with
      measures of cognitive function, including general intelligence, verbal and visual
      memory, and executive performance. CONCLUSIONS: These findings in SPD suggest
      altered fronto-temporal connectivity through the UF, similar to findings in
      schizophrenia, and intact neocortical-limbic connectivity through the CB, in
      marked contrast with what has been reported in schizophrenia.

PMID- 15978552
TI  - Alzheimer disease subjects with psychosis have increased schizotypal symptoms
      before dementia onset.
AB  - BACKGROUND: Recent findings have demonstrated the familiality of psychotic
      symptoms occurring during Alzheimer disease (AD with psychosis, AD+P),
      particularly for subjects with multiple psychotic symptoms. We have proposed a
      model in which genes that confer a small risk for psychosis interact with
      neurodegenerative illness to yield manifest psychotic symptoms during AD. One
      prediction of this model would be that AD+P subjects would have evidence of
      increased degrees of subsyndromal psychosis before AD onset. METHODS: We used the
      psychosis (positive symptoms) and psychotic personality disorder sections
      (paranoid, schizoid, and schizotypal) of the Family Interview for Genetic Studies
      (FIGS) to interview the primary caregivers of AD subjects. Caregivers were
      specifically instructed to answer questions with regard to the subject's behavior
      before AD onset. Interviewers were blind to presence of psychosis during AD.
      Subjects were grouped by whether they had at least one or had multiple psychotic
      symptoms during AD. RESULTS: Scores on the FIGS subscales were generally low,
      reflecting a low frequency of endorsement of psychotic symptoms before AD. There
      was a trend for the schizotypal scores to be elevated in the AD+P group, which
      was highly significant in the AD+P group with multiple psychotic symptoms. There
      was no significant association of paranoid or schizoid scores with either group.
      CONCLUSIONS: Although limited by small sample size and retrospective design,
      these data are novel in that they indicate an association of subsyndromal
      psychotic symptoms before AD onset with psychosis in AD. Subsyndromal psychosis
      might be useful for classifying AD+P families for genetic mapping studies.
      Prospective confirmation is required.

PMID- 15978553
TI  - Neurobiological correlates of social conformity and independence during mental
      rotation.
AB  - BACKGROUND: When individual judgment conflicts with a group, the individual will
      often conform his judgment to that of the group. Conformity might arise at an
      executive level of decision making, or it might arise because the social setting
      alters the individual's perception of the world. METHODS: We used functional
      magnetic resonance imaging and a task of mental rotation in the context of peer
      pressure to investigate the neural basis of individualistic and conforming
      behavior in the face of wrong information. RESULTS: Conformity was associated
      with functional changes in an occipital-parietal network, especially when the
      wrong information originated from other people. Independence was associated with
      increased amygdala and caudate activity, findings consistent with the assumptions
      of social norm theory about the behavioral saliency of standing alone.
      CONCLUSIONS: These findings provide the first biological evidence for the
      involvement of perceptual and emotional processes during social conformity.

PMID- 15978554
TI  - Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia
      in schizophrenic subjects.
AB  - BACKGROUND: Primary polydipsia is a common complication in patients with chronic
      psychoses, particularly schizophrenia. Disease pathogenesis is poorly understood,
      but one contributory factor is thought to be dopamine dysregulation caused by
      prolonged treatment with neuroleptics. Both angiotensin-converting enzyme (ACE)
      and orexin (hypocretin) signaling can modulate drinking behavior through
      interactions with the dopaminergic system. METHODS: We performed association
      studies on the insertion/deletion (I/D) sequence polymorphism of ACE and single
      nucleotide polymorphisms within the prepro-orexin (HCRT), orexin receptor 1
      (HCRTR1), and orexin receptor 2 (HCRTR2) genes. Genotypes were determined by
      polymerase chain reaction amplification, followed by either electrophoretic
      separation or direct sequencing. RESULTS: The ACE I/D polymorphism showed no
      association with polydipsic schizophrenia. Screening of the orexin signaling
      system detected a 408 isoleucine to valine mutation in HCRTR1 that showed
      significant genotypic association with polydipsic-hyponatremic schizophrenia (p =
      .012). The accumulation of this mutation was most pronounced in polydipsic versus
      nonpolydipsic schizophrenia (p = .0002 and p = .008, for the respective genotypic
      and allelic associations). The calcium mobilization properties and the protein
      localization of mutant HCRTR1 seem to be unaltered. CONCLUSION: Our preliminary
      data suggest that mutation carriers might have an increased susceptibility to
      polydipsia through an undetermined mechanism.

PMID- 15978555
TI  - Activation of the trigeminal medullary dorsal horn during voluntary diving in
      rats.
AB  - Fos immunohistochemistry was used to indicate whether activation of trigeminal
      neurons occurs in voluntarily diving rats. In rats trained to dive underwater,
      significant increases in Fos labeling were found within the ventral superficial
      MDH and paratrigeminal nucleus, 100-150 microm caudal to the obex compared to
      control rats. The conclusion is that the ventral superficial MDH is the initial
      brainstem afferent relay of diving response in voluntarily diving rats.

PMID- 15978556
TI  - Amplitude/frequency of spontaneous mEPSC correlates to the degree of long-term
      depression in the CA1 region of the hippocampal slice.
AB  - Prior synaptic or cellular activity influences degree or threshold for subsequent
      induction of synaptic plasticity, a process known as metaplasticity. Thus, the
      continual synaptic activity, spontaneous miniature excitatory synaptic current
      (mEPSC) may correlate to the induction of long-term depression (LTD). Here, we
      recorded whole-cell EPSC and mEPSC alternately in the Schaffer-CA1 synapses in
      brain slice of young rats, and found that this recording configuration affected
      neither EPSC nor mEPSC. Low frequency stimulation (LFS) induced variable
      magnitudes of LTD. Remarkably, larger magnitudes of LTD were significantly
      correlated to smaller amplitude/lower frequency of the basal mEPSC. Furthermore,
      under the conditions reduced amplitude/frequency of the basal mEPSC by exposure
      to behavioral stress immediately before slice preparation or low concentration of
      calcium in bath solution, the magnitudes of LTD were still inversely correlated
      to mEPSC amplitude/frequency. These new findings suggest that spontaneous mEPSC
      may reflect functional and/or structural aspects of the synapses, the synaptic
      history ongoing metaplasticity.

PMID- 15978557
TI  - Circadian rhythm of Period1 clock gene expression in NOS amacrine cells of the
      mouse retina.
AB  - The vertebrate retina contains self-sustained circadian clocks that broadly
      influence retinal physiology. In the present study, we have examined the
      relationship of nitric oxide, GABAergic and glycinergic inner retinal neurons
      with expression of a reporter for the circadian clock gene Period1 (Per1). Using
      Per1 : :GFP transgenic mice, we found that 72% of brain nitric oxide synthase
      (bNOS) expressing amacrine cells (NOS amacrine cells) sampled during the daytime
      were also immunoreactive for Per1-driven GFP. The number of bright GFP(+) NOS(+)
      cells was greater at Zeitgeber time (ZT) 10 than at 22, and this pattern
      persisted in retinas from animals which were placed in constant darkness
      [Circadian time (CT) 10 vs. 22]. Intensities of GFP-IR for individual NOS
      amacrine cells were analyzed at ZT4, 10, 16 and 22, with the peak value occurring
      at ZT10. Similar results were obtained from retinas sampled at CT4, 10, 16 and 22
      in constant darkness, indicating that an endogenous circadian clock drives the
      transcription of the Per1 clock gene within NOS amacrine cells. The predominance
      of Per1 : :GFP(+) amacrine cells (82%), was immunoreactive to glutamate
      decarboxylase 65, but no Per1 : :GFP(+) amacrine cells colabeled with a glycine
      transporter 1 antibody. The results demonstrate circadian rhythms in Per1
      promoter activation in nitric oxide (NO) and GABA secreting amacrine cells, and
      suggest that NO and GABA could be controlled by circadian clock mechanisms in the
      mammalian retina.

PMID- 15978558
TI  - Immunohistochemical study on the distribution of phosphorylated extracellular
      signal-regulated kinase (ERK) in the central nervous system of SOD1G93A
      transgenic mice.
AB  - In the present study, we performed immunohistochemical studies to investigate the
      changes of phosphorylated extracellular signal-regulated kinases (pERK) in the
      central nervous system of SOD1(G93A) transgenic mice. In symptomatic transgenic
      mice, pERK-immunoreactive astrocytes were detected in the spinal cord, brainstem,
      central gray and cerebellar nuclei. In contrast to symptomatic mice, no pERK
      immunoreactive astrocytes were observed in any brain region of wtSOD1 and
      presymptomatic mice, and the number and intensity of stained neurons were not
      different at the age of 8 weeks and 13 weeks. Interestingly, region-specific
      alterations in pERK immunoreactivity were observed in the hippocampal region and
      cerebellum. These results provide the first evidence that pERK-immunoreactive
      astrocytes were found in the CNS of SOD1(G93A) transgenic mice after clinical
      symptoms, showing a possible consequence of the pathological process of ALS. This
      study has also demonstrated that pERK increases in the hippocampus and
      cerebellum, suggesting a role of pERK in an abnormality of cognitive and/or motor
      function in ALS, respectively. However, the mechanisms underlying the increased
      immunoreactivity for pERK and the functional implications require elucidation.

PMID- 15978559
TI  - Colocalization of CART with substance P but not enkephalin in the rat nucleus
      accumbens.
AB  - CART peptide is a novel neurotransmitter that, due to its distribution in the
      brain and its modulation of dopamine systems, may be involved in aspects of
      reward and drug abuse. In the nucleus accumbens (NAcc), CART peptide
      immunoreactivity (IR) is colocalized with substance P-IR in neurons.
      Approximately 86% of CART-IR cells colocalize with substance P, while only 19% of
      substance P-IR neurons contain CART. CART peptide does not colocalize with
      enkephalin-IR in this region. The substance P-CART colocalization exists in a
      rostro-caudal gradient with more colocalization in rostral regions. The presence
      of CART in substance P NAcc neurons suggests that CART neurons may be a subset of
      the basal ganglia direct pathway or that CART neurons are involved in limbic
      projections of the NAcc, such as to the ventral pallidum.

PMID- 15978560
TI  - Fos responses to short-term adaptation of the horizontal vestibuloocular reflex
      before and after vestibular compensation in the Mongolian gerbil.
AB  - Fos expression in vestibular brainstem and cerebellar regions was evaluated
      during vestibular adaptation in the Mongolian gerbil. In addition, vestibular
      adaptation was evaluated in both normal and compensated animals, as vestibular
      compensation reorganizes the vestibular pathway constraining adaptive processes.
      Behaviorally, discordant optokinetic and vestibular input induced appropriate
      high and low gain in horizontal angular vestibuloocular reflex responses. In
      normal animals, low gain adaptation was more complete than high gain. However, in
      compensated animals, only low gain adaptation produced adaptive responses both
      toward and away from the lesion with appropriate gain shifts. High gain
      adaptation in compensated animals failed to result in gain adaptation for head
      movements toward the side of the lesion. Fos expression during acute vestibular
      adaptation in normal animals was found in the flocculus/paraflocculus, the dorsal
      cap of the inferior olive (IOK), and the prepositus hypoglossi (PrH). Floccular
      Fos labeling was increased under both high and low gain conditions. IOK and PrH
      labeling was increased and correlated during low gain conditions, but was reduced
      and uncorrelated during high gain conditions. The pattern of Fos labeling in
      compensated animals was asymmetric-favoring the ipsilesional flocculus and
      contralesional vestibular brainstem. Both compensated high and low gain
      adaptation groups displayed increased floccular and IOK Fos labeling, but only
      compensated high gain adaptation produced increased Fos labeling in the medial
      vestibular nucleus. The behavioral and Fos labeling results are consistent with
      visual-vestibular adaptation requiring direct vestibular input.

PMID- 15978562
TI  - Dendritic cells acquire tolerogenic properties at the site of sterile
      granulomatous inflammation.
AB  - Subcutaneous implantation of polyvinyl sponges represents a suitable model for
      studying the mechanisms of acute and chronic inflammation, granulomatous foreign
      body reaction, as well as wound healing. Using such a model in rats, we studied
      the phenotypic and functional characteristics of dendritic cells (DC). DC were
      purified from the sponge exudate using a combination of separation gradients,
      adherence to plastics, and immunomagnetic sorting. We have shown that the number
      of DC progressively increased in the sponges, reaching maximal values at day 10
      after implantation, followed by their decrease thereafter. Inflammatory DC
      expressed MHC class II molecules and myeloid markers CD11b, CD11c, and CD68. A
      subset of DC expressed CD4, R-MC46, DEC-205, R-MC17, and CCR1. Compared to DC
      isolated in the early phase of inflammation (day 6 DC), DC in the late stage of
      inflammation (day 14 DC) had a lower capability to stimulate the proliferation of
      allogeneic lymphocytes and CD4(+) T cells. This finding correlated with the
      downregulation of CD80, CD86, and CD54 expression and the increased proportion of
      plasmacytoid MHC class II(+) His 24(+) His 48(+) DC. The suppression of
      allogeneic lymphocyte proliferation was abrogated by the treatment of DC with
      lipopolysaccharide. In addition, day 14 DC exerted tolerogenic capability in co
      culture with allogenic CD4(+) T cells. These results correlated with the
      increased levels of IL-10 and TGF-beta in culture supernatants and the sponge
      exudate.

PMID- 15978561
TI  - Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by
      ventricular stretch.
AB  - OBJECTIVE: Cardiotrophin-1 (CT-1) is an interleukin-6-related cytokine with known
      hypertrophic and protective actions upon cardiac myocytes. We provide here the
      first report of cardiac tissue and plasma levels of CT-1 in human and
      experimental hypertension, demonstrate cardiac CT-1 secretion stimulated by
      ventricular stretch, and characterise molecular forms of CT-1 in tissue and
      plasma. METHODS: CT-1 levels in human and rat plasma and in rat cardiac tissue
      extracts were determined by specific radioimmunoassay (RIA). Cardiac CT-1
      secretion during ventricular stretch was studied in isolated, perfused hearts.
      Molecular forms of CT-1 were identified using RIA coupled with high performance
      liquid chromatography (HPLC). Results are given as mean+/-SEM. RESULTS: Plasma
      levels of CT-1 in patients with untreated hypertension (UTH, 606+/-18 pmol/L,
      n=24) were significantly higher than those in age-and BMI-matched normotensive
      volunteers (NT, 546+/-12 pmol/L, n=31, P<0.01 vs. UTH). CT-1 levels in matched
      patients with treated hypertension (THT, 618+/-10 pmol/L, n=35) were similar to
      those in UTH patients, but higher than in NT controls (P<0.01). Plasma CT-1
      demonstrated a weak but significant correlation with systolic blood pressure in
      all patients (r=0.241, P<0.05, n=90). In contrast, CT-1 levels in male, 40-week
      old, NT-WKY rats (1295+/-98 pmol/L) were significantly higher than those in
      matched UTH-SHR (937+/-31 pmol/L, P<0.01). In both WKY and SHR rats, atrial
      tissue concentrations of CT-1 were 8-fold higher than ventricular levels. Left
      ventricular tissue CT-1 protein concentrations were significantly higher in 40
      week-old SHR compared with age-matched WKY (SHR 12.6+/-0.5 fmol/g vs. WKY 9.5+/
      0.8 fmol/g, P<0.01). Ventricular stretch of Langendorff perfused, isolated
      WKY/SHR hearts resulted in significant, acute release of CT-1 and BNP. HPLC
      coupled with specific RIA revealed CT-1 in human/rat plasma, isolated rat heart
      perfusate, and rat heart tissue extracts to consist of complex, high molecular
      weight forms. CONCLUSIONS: This is the first report to show increased levels of
      plasma CT-1 in hypertensive disease. CT-1 is a unique cardiac cytokine whose
      release is stimulated by ventricular stretch. The atrium contains the highest
      levels of the protein. The stored and circulating molecular form of CT-1 is
      complex, which may modulate its in vivo role in cardiovascular disease.

PMID- 15978563
TI  - Molecular and cellular interactions in chronic inflammatory autoimmune diseases.
      Proceedings of the European Federation of Immunological Societies Belgrade
      symposium on chronic inflammatory autoimmune diseases. September, 2004. Belgrade,
      Serbia.

PMID- 15978564
TI  - Quantification of glutaric and 3-hydroxyglutaric acids in urine of glutaric
      acidemia type I patients by HPLC with intramolecular excimer-forming fluorescence
      derivatization.
AB  - BACKGROUND: Glutaric aciduria type I (GA1) is an autosomal recessive disorder
      that usually causes neurological damage. Early diagnosis of the disease prior to
      the appearance of clinical symptoms can lead to better outcomes. METHODS: We
      describe a simple and selective HPLC method with intramolecular excimer-forming
      fluorescence derivatization to diagnose GA1. Glutaric acid (GA) and 3
      hydroxyglutaric acid (3HGA) in urine and an internal standard were derivatized
      with 1-pyrenebutyric hydrazide (PBH). The derivatives were separated on a C18
      column and fluorometrically detected at 475 nm (excitation of 345 nm) with a run
      time of 18 min. RESULTS: Excellent linearity over a wide range, reproducibility
      (coefficient of variation < or =14.5%), and sensitivity (limit of detection 0.4
      micromol/l 3HGA and 0.2 micromol/l GA) were obtained. A retrospective study on
      previously diagnosed GA1 patients' urine from our laboratory archives between
      1999 and 2004 was performed by analysts blinded to the study. CONCLUSIONS: The
      method enabled us to differentiate GA1 cases (n=36) from controls (n=99),
      regardless of the years of urine storage. The method is valuable for both
      retrospective and prospective diagnoses of GA1.

PMID- 15978565
TI  - The DNA isolation method has effect on allele drop-out and on the results of
      fluorescent PCR and DNA fragment analysis.
AB  - BACKGROUND: The quality and the quantity of isolated DNA have an effect on PCR
      amplifications. METHODS: The authors studied three DNA isolation protocols (resin
      binding method using fresh and frozen amniotic fluid samples, and silica
      adsorption method using fresh samples) on the quantity and on the quality of the
      isolated DNA. Amniotic fluid samples were obtained from 20 pregnant women. The
      isolated DNA concentrations were determined by real-time fluorimeter using
      SYBRGreen I method. Each sample was studied for the presence of 8 STR markers.
      The authors compared the number of the detected alleles, electrophoretograms and
      peak areas. RESULTS: There was a significant difference between the concentration
      of the obtained DNA and in the peak areas between the three isolation protocols.
      The numbers of detected alleles were different, we observed the most allele drop
      outs in the resin type DNA isolation protocol from the fresh sample (detected
      allele numbers 182), followed by resin binding protocol from the frozen samples
      (detected allele number 243) and by the silica adsorption method (detected allele
      number 264). CONCLUSIONS: The authors demonstrated that the DNA isolation method
      has an effect on the quantity and quality of the isolated DNA, and on further PCR
      amplifications.

PMID- 15978566
TI  - Protein S and protein C gene mutations in Japanese deep vein thrombosis patients.
AB  - OBJECTIVES: Coagulation factor V Leiden has not been detected in Japanese
      patients suffering from thrombosis. Hitherto, the constitutional background of
      Japanese thrombotic patients has never been systematically examined. We have
      performed a systematic investigation to determine pathogenesis for deep vein
      thrombosis in a Japanese population. DESIGN AND METHODS: Routine coagulation and
      fibrinolysis tests were performed to determine the activities of protein S,
      protein C, antithrombin, plasminogen and fibrinogen. Gene analysis was performed
      in thrombotic patients having low activities of these factors. RESULTS: Our study
      indicates that the frequency (19/85 = 0.22) of mutations of protein S gene in the
      Japanese patients was 5-10 times higher than that of mutations of protein S gene
      in Caucasian patients, and the frequency (8/85 = 0.09) of mutations of protein C
      gene was almost three times higher than that of Caucasian patients. The frequency
      of antithrombin gene mutation was similar in both populations. CONCLUSION: Our
      study reinforces that the genetic anomaly in the protein S/protein C
      anticoagulation system is an important risk factor for thrombophilia in the
      Japanese population.

PMID- 15978567
TI  - Visual evoked potentials discrimination based on adaptive zero-tracking neural
      network.
AB  - A non-linear classifier is proposed to discriminate visual evoked potentials
      (VEP). It combines two techniques: the zero-tracking method and a multi-layer
      network. The first method consists of processing the VEP data through an adaptive
      linear prediction filter aiming at extracting the appropriate feature vector to
      be fed into the neural network. 105 VEPs collected from 48 healthy people and 57
      patients are analysed to test the performances of the proposed classifier. The
      results obtained with a back-propagation network revealed a total success rate
      equal to 89%. It is also found more accurate than the latency method used in
      hospitals.

PMID- 15978568
TI  - Patient-recognition data-mining model for BCG-plus interferon immunotherapy
      bladder cancer treatment.
AB  - Bladder cancer is the fifth most common malignant disease in the United States
      with an annual incidence of around 63,210 new cases and 13,180 deaths. The cost
      for providing care for patients with bladder cancer disease is high. Bladder
      cancer treatment options such as immunotherapy, chemotherapy, radiation therapy,
      transurethral resection, and cystectomy, are used with varying success rates. In
      this research, data from a nationwide bacillus Calmette-Gue rin (BCG) plus
      interferon-alpha (IFN-alpha) immunotherapy clinical trial was considered. Data
      mining algorithms were used to analyze the effectiveness of immunotherapy
      treatment and to understand the prominent parameters and their interactions. The
      extracted knowledge was used to build a patient recognition model for prediction
      of treatment outcomes. The data was analyzed to understand the impact of various
      parameters on the treatment outcome. A list of significant parameters such as
      cumulative tumor size, presence of residual disease, stages of prior bladder
      cancer, current state of bladder cancer, and the presence of current bladder
      cancer (T1) is provided. The decision-making approach outlined in the paper
      supplemented with additional knowledge bases will lead to a comprehensive
      analytical road map of the BCG/IFN-alpha immunotherapy treatment. It will provide
      individualized guidelines for each stage of the treatment as well as measure the
      success of the treatment.

PMID- 15978569
TI  - A novel ensemble machine learning for robust microarray data classification.
AB  - Microarray data analysis and classification has demonstrated convincingly that it
      provides an effective methodology for the effective diagnosis of diseases and
      cancers. Although much research has been performed on applying machine learning
      techniques for microarray data classification during the past years, it has been
      shown that conventional machine learning techniques have intrinsic drawbacks in
      achieving accurate and robust classifications. This paper presents a novel
      ensemble machine learning approach for the development of robust microarray data
      classification. Different from the conventional ensemble learning techniques, the
      approach presented begins with generating a pool of candidate base classifiers
      based on the gene sub-sampling and then the selection of a sub-set of appropriate
      base classifiers to construct the classification committee based on classifier
      clustering. Experimental results have demonstrated that the classifiers
      constructed by the proposed method outperforms not only the classifiers generated
      by the conventional machine learning but also the classifiers generated by two
      widely used conventional ensemble learning methods (bagging and boosting).

PMID- 15978570
TI  - The intron 5/6 promoter region of the ship1 gene regulates expression in
      stem/progenitor cells of the mouse embryo.
AB  - The s-SHIP protein is a shorter isoform of the longer SHIP1 protein and lacks the
      N-terminal SH2 domain region contained in SHIP1. s-SHIP is expressed in ES cells
      and in enriched bone marrow stem cells, and may be controlled by a promoter
      within intron 5 of the ship1 gene. We therefore examined the potential
      specificity of promoter activity in ES cells of an intron 5/intron 6 ship1
      genomic segment and its tissue specificity within transgenic mice expressing GFP
      from this promoter region. The results indicate that s-SHIP promoter activity is
      specific for ES cells in vitro and for known and presumptive stem/progenitor
      cells throughout embryo development of the transgenic mice. Specific GFP
      expression was observed in the blastocyst, primordial germ cells, thymus,
      arterioles, osteoblasts, and skin epidermis. The epidermis/epithelium is the
      progenitor for hair follicles, mammary tissue, and prostate. Interestingly, each
      of these latter tissues acquired a few GFP-positive cells in the course of their
      development from the epithelial layers, and these cells express marker proteins
      for stem/progenitor cells. These results identify potential stem cell
      populations, mark these cells for analyses in normal and cancer development, and
      implicate s-SHIP as an important protein in stem/progenitor cell function.

PMID- 15978571
TI  - Notch1 is essential for postnatal hair follicle development and homeostasis.
AB  - Notch genes encode evolutionarily conserved large, single transmembrane
      receptors, which regulate many cell fate decisions and differentiation processes
      during fetal and postnatal life. Multiple Notch receptors and ligands are
      expressed in both developing and adult epidermis and hair follicles.
      Proliferation and differentiation of these two ectodermal-derived structures have
      been proposed to be controlled in part by the Notch pathway. Whether Notch
      signaling is involved in postnatal hair homeostasis is currently unknown. Here,
      we investigate and compare the role of the Notch1 receptor during embryonic hair
      follicle development and postnatal hair homeostasis using Cre-loxP based tissue
      specific and inducible loss-of-function approaches. During embryonic development,
      tissue-specific ablation of Notch1 does not perturb formation and patterning of
      hair follicle placodes. However, Notch1 deficient hair follicles invaginate
      prematurely into the dermis. Embryonic as well as postnatal inactivation of
      Notch1 shortly after birth or in adult mice results in almost complete hair loss
      followed by cyst formation. The first hair cycle of Notch1 deficient mice is
      characterized by shortened anagen and a premature entry into catagen. These data
      show that Notch1 is essential for late stages of hair follicle development during
      embryogenesis as well as for post-natal hair follicle development and hair
      homeostasis.

PMID- 15978572
TI  - Effect of a cyclohexenonic long-chain fatty alcohol on calcium mobilization.
AB  - Cyclohexenonic long-chain fatty alcohols constitute a family of synthetic
      compounds with trophic, secretagogue and antioxidant properties. Despite their
      multiple biological actions in neuronal and non-neuronal tissues, the
      intracellular mechanisms underlying CFA activity remain unknown. In the present
      study, we show that 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one
      (tCFA15) directly mobilizes Ca(2+) in the pituitary neural lobe synaptosomes and
      in primary sensory neurons from dorsal root ganglia. This effect is dependent on
      the presence of extracellular Ca(2+), but does not involve transmembrane voltage
      operated calcium channels. Using a combination of pharmacological agents that
      block or deplete intracellular Ca(2+) stores, our results suggest the implication
      of a calcium induced-calcium release mechanism evoked by tCFA15-induced Ca(2+)
      influx. To our knowledge, these findings constitute the first attempt towards the
      comprehension of the biological actions of cyclohexenonic long-chain fatty
      alcohols at a molecular level.

PMID- 15978573
TI  - alpha(2A)-Adrenoceptors regulate d-amphetamine-induced hyperactivity and
      behavioural sensitization in mice.
AB  - Stimulants, such as d-amphetamine, enhance the release of dopamine in the central
      nervous system (CNS) and induce locomotor activation in mice. When amphetamine is
      administered repeatedly, the locomotor activation is progressively increased.
      This behavioural sensitization may be associated with the development of drug
      craving, addiction and dependence. Also noradrenergic mechanisms participate in
      the mediation of the effects of psychostimulants. In this study we show that mice
      lacking the alpha(2)-adrenoceptor subtype A (alpha(2A)-AR knock-out (KO) on
      C57Bl/6J background) are supersensitive to the acute locomotor effects of d
      amphetamine (5 mg/kg) in a novel environment compared to wild-type (WT) control
      mice. When both genotypes were treated repeatedly with d-amphetamine (2 mg/kg)
      they developed locomotor hyperactivation (sensitization), but its amplitude was
      lower in alpha(2A)-AR KO mice. Development of hyperactivation was reduced in both
      genotypes by pretreatment with the selective alpha(2)-adrenoceptor antagonist,
      atipamezole (1 mg/kg). Acute atipamezole also attenuated the expression of d
      amphetamine-induced behavioural sensitization especially in WT mice.
      Interestingly, alpha(2A)-AR KO mice failed to exhibit persistent sensitization
      after 2 weeks of abstinence from repeated d-amphetamine. Rewarding properties of
      d-amphetamine, measured by conditioned place preference, were similar in both
      genotypes. These findings indicate that d-amphetamine-induced acute and
      sensitized locomotor effects are controlled by alpha(2)-adrenoceptors. Drugs
      antagonizing the alpha(2A)-adrenoceptor subtype may provide a novel approach for
      reducing drug sensitization and motor complications caused by dopaminergic
      agents.

PMID- 15978574
TI  - Effect of vilazodone on 5-HT efflux and re-uptake in the guinea-pig dorsal raphe
      nucleus.
AB  - The effect of vilazodone, a putative selective serotonin re-uptake inhibitor
      (SSRI) with 5-HT (5-hydroxytryptamine)(1A) receptor partial agonist activity, was
      investigated on 5-HT efflux and 5-HT re-uptake half life in the guinea-pig dorsal
      raphe nucleus, using in vitro fast cyclic voltammetry. The SSRI, fluoxetine,
      significantly increased 5-HT efflux. In contrast, vilazodone had no effect on 5
      HT efflux at 100 nM but significantly decreased 5-HT efflux at 1 microM. Co
      perfusion of 8-OH-DPAT (+/-8-hydroxy-2-(di-n-propylamino)tetralin) with
      fluoxetine significantly attenuated the fluoxetine-induced increase in 5-HT
      efflux. Co-perfusion of WAY 100635 with vilazodone did not attenuate the effect
      of vilazodone alone. In addition, the re-uptake half life for 5-HT was
      significantly increased by both fluoxetine and vilazodone. In conclusion, we have
      demonstrated that vilazodone (100 nM, 1 microM), in the guinea-pig dorsal raphe
      nucleus, blocks the serotonin transporter but does not display 5-HT(1A) receptor
      agonism.

PMID- 15978575
TI  - Pharmacological characterization of the TRPV1 receptor antagonist JYL1421
      (SC0030) in vitro and in vivo in the rat.
AB  - The TRPV1 capsaicin receptor is an integrator molecule on primary afferent
      neurones participating in inflammatory and nociceptive processes. The present
      paper characterizes the effects of JYL1421 (SC0030), a TRPV1 receptor antagonist,
      on capsaicin-evoked responses both in vitro and in vivo in the rat. JYL1421
      concentration-dependently (0.1-2 microM) inhibited capsaicin-evoked substance P,
      calcitonin gene-related peptide and somatostatin release from isolated tracheae,
      while only 2 microM resulted in a significant inhibition of electrically induced
      neuropeptide release. Capsazepine (0.1-2 microM), as a reference compound,
      similarly diminished both capsaicin-evoked and electrically evoked peptide
      release. JYL1421 concentration-dependently decreased capsaicin-induced Ca(2+)
      accumulation in cultured trigeminal ganglion cells, while capsazepine was much
      less effective. In vivo 2 mg/kg i.p. JYL1421, but not capsazepine, inhibited
      capsaicin-induced hypothermia, eye wiping movements and reflex hypotension (a
      component of the pulmonary chemoreflex or Bezold-Jarisch reflex). Based on these
      data JYL1421 is a more selective and in most models also a more potent TRPV1
      receptor antagonist than capsazepine, therefore it may promote the assessment of
      the (patho)physiological roles of the TRPV1 receptor.

PMID- 15978576
TI  - An archaeal SET domain protein exhibits distinct lysine methyltransferase
      activity towards DNA-associated protein MC1-alpha.
AB  - The evolutionarily conserved SET domain proteins in eukaryotes have been shown to
      function as site-specific histone lysine methyltransferases, and play an
      important role in regulating chromatin-mediated gene transcriptional activation
      and silencing. Structure-based sequence analysis has revealed that SET domains
      are also encoded by viruses and bacteria, as well as Archaea. However, their
      cellular functions remain elusive. In this study, we have characterized a SET
      domain protein from Methanosarcina mazei strain Go1 that we refer to as Go1-SET.
      We show that Go1-SET exists as a homodimer in solution, and functions as a lysine
      methyltransferase with high substrate specificity that is dependent on the amino
      acid sequence flanking the lysine methylation site. Particularly, Go1-SET
      exhibits selective methyltransferase activity towards one of the major archaeal
      DNA interacting protein MC1-alpha at lysine 37. Our findings suggest that SET
      domain proteins such as Go1-SET may restructure archaeal chromatin that is
      composed of MC1-DNA complexes, and that modulation of chromatin structure by
      lysine methylation may have arisen before the divergence of the archaeal and
      eukaryotic lineages.

PMID- 15978577
TI  - Transmembrane homodimerization of receptor-like protein tyrosine phosphatases.
AB  - Receptor-like protein tyrosine phosphatases (RPTPs) are type I integral membrane
      proteins. Together with protein tyrosine kinases, RPTPs regulate the
      phosphotyrosine levels in the cell. Studies of two RPTPs, CD45 and PTPalpha, have
      provided strong evidence that dimerization leads to inactivation of the
      receptors, and that the dimerization of PTPalpha involves interactions in the
      transmembrane domain (TMD). Using the TOXCAT assay, a genetic approach for
      analyzing TM interactions in Escherichia coli membranes, we show that the TMD of
      RPTPs interact in the membrane, albeit to different extents. Using fusion
      proteins of TMDs, we also observe an equilibrium between monomer and dimer in
      sodium dodecyl sulfate (SDS) micelles. Through a mutational study of the DEP1
      TMD, we demonstrate that these interactions are specific. Taken together, our
      results define a subset of the RPTP family in which TM homodimerization may act
      as a mediator of protein function.

PMID- 15978578
TI  - Identification of human fetal liver miRNAs by a novel method.
AB  - MicroRNAs (miRNAs) are short 20-25 nucleotides RNA molecules that have been shown
      to regulate gene expressions in a variety of eukaryotic systems. miRNAs are
      widespread in eukaryotes and several hundred of miRNAs have been identified, but
      still a lot of miRNAs have not been detected in various eukaryotic organisms.
      However, it is not an easy work to clone miRNAs by traditional methods. Here, we
      describe the identification of 27 miRNAs from a human fetal liver cDNA library by
      a novel cloning method. Low molecular weight RNA fraction (< or = 200 nt) from
      fetal liver tissue was extracted, and polyadenylated by poly(A) polymerase. A 5'
      RNA adaptor was ligated to poly(A)-tailed RNA using T4 RNA ligase. After reverse
      transcription, the cDNA was amplified by PCR with two adaptor primers. The PCR
      product with a size about 109 bp was recovered and cloned into T vector. After
      sequencing, database searching, and expression profiling, 5 novel miRNAs were
      discovered among other 22 known miRNAs in human fetal liver. These finding
      indicate that a large diverse population of miRNAs may function to regulate gene
      expression in hepatocyte.

PMID- 15978579
TI  - Alternative splicing regulates the transcriptional activity of Drosophila heat
      shock transcription factor in response to heat/cold stress.
AB  - Heat shock transcription factor 1 (HSF1) mediates the induction of heat shock
      proteins in response to various types of stress. Although HSF1 activity is
      regulated by its post-translational modifications, alterations in mRNA expression
      have also been suggested. We here identified three new alternatively spliced
      isoforms of Drosophila HSF (dHSF) mRNA, named dHSFb, dHSFc, and dHSFd. We found
      that the ratio of dHSFb increases upon heat exposure, while that of dHSFd
      increases upon cold exposure. The dHSFc and dHSFd isoforms showed greater
      transcriptional activity than the other isoforms. Our findings suggest that
      alternative splicing regulates the transcriptional activity of dHSF.

PMID- 15978580
TI  - Crystal structure of the ubiquitin-like protein YukD from Bacillus subtilis.
AB  - The YukD protein in Bacillus subtilis was identified in a hidden Markov model
      (HMM) search as being related in sequence to ubiquitin. By solving the crystal
      structure we show that YukD adopts a fold that is most closely related to
      ubiquitin, yet has the shortest C-terminal tail of all known ubiquitin-like
      proteins. The endogenous gene of yukD in B. subtilis was disrupted without an
      obvious phenotypic effect and an inducible copy encoding a C-Myc and His-tagged
      version of the protein was introduced at the ectopic locus amyE. Conjugation
      assays performed both in vitro and in vivo indicate that YukD lacks the capacity
      for covalent bond formation with other proteins.

PMID- 15978581
TI  - Peroxisome proliferator-activated receptor delta as a molecular target to
      regulate lung cancer cell growth.
AB  - It has been assumed that prostaglandin (PG)I2 signaling contributes to the
      negative growth control of lung cancer cells; however, the mechanism remains
      unresolved. PGI2 functions through a cell surface G protein-coupled receptor
      (prostaglandin I2-binding receptor, IP) and also exerts an effect by interacting
      with a nuclear hormone receptor, peroxisome proliferator-activated receptor delta
      (PPARdelta). We found that PPARdelta was a key molecule of PGI2 signaling to give
      negative growth control of lung cancer cells (A549), using carbarprostacyclin, a
      PGI2 agonist for IP and PPARdelta, and L-165041, a PPARdelta agonist.
      Furthermore, PPARdelta-induced cell growth control was reinforced by the
      inhibition of cyclooxygenase. These results suggest that PPARdelta activation
      under the suppression of PG synthesis is important to regulate lung cancer cell
      growth.

PMID- 15978582
TI  - Semaphorin 4B interacts with the post-synaptic density protein PSD-95/SAP90 and
      is recruited to synapses through a C-terminal PDZ-binding motif.
AB  - The semaphorins are a large family of proteins that act as guidance signals for
      axons and dendrites. The class 4 semaphorins are integral membrane proteins that
      are widely expressed throughout the nervous system. Here, we show that a subclass
      of these semaphorins is characterized by a PDZ-binding motif at their carboxy
      terminus. This sequence mediates the interaction with the post-synaptic density
      protein PSD-95/SAP90. Co-expression of Sema4B with PSD-95 in COS 7 cells results
      in the clustering of Sema4B. Sema4B co-localizes with PSD-95 at synaptic contacts
      between cultured hippocampal neurons. This synaptic localization depends on the
      presence of the PDZ-binding motif.

PMID- 15978583
TI  - Nitrite as the major source of nitric oxide production by Arabidopsis thaliana in
      response to Pseudomonas syringae.
AB  - The origin of nitric oxide (*NO) in plants is unclear and an *NO synthase (NOS)
      like enzyme and nitrate reductase (NR) are claimed as potential sources. Here we
      used wild-type and NR-defective double mutant plants to investigate *NO
      production in Arabidopsis thaliana in response to Pseudomonas syringae pv
      maculicola. NOS activity increased substantially in leaves inoculated with P.
      syringae. However, electron paramagnetic resonance experiments showed a much
      higher *NO formation that was dependent on nitrite and mitochondrial electron
      transport rather than on arginine or nitrate. Overall, these results indicate
      that NOS, NR and a mitochondrial-dependent nitrite-reducing activity cooperate to
      produce *NO during A. thaliana-P. syringae interaction.

PMID- 15978584
TI  - Identification of a villin-related tobacco protein as a novel cross-reactive
      plant allergen.
AB  - In a paradigmatic approach we identified cross-reactive plant allergens for
      allergy diagnosis and treatment by screening of a tobacco leaf complementary DNA
      (cDNA) library with serum IgE from a polysensitized allergic patient. Two IgE
      reactive cDNA clones were isolated which code for proteins with significant
      sequence similarity to the actin-binding protein, villin. Northern- and Western
      blotting demonstrate expression of the villin-related allergens in pollen and
      somatic plant tissues. In addition, villin-related proteins were detected in
      several plant allergen sources (tree-, grass-, weed pollen, fruits, vegetables,
      nuts). A recombinant C-terminal fragment of the villin-related protein was
      expressed in Escherichia coli, purified and shown to react specifically with
      allergic patients IgE. After profilin, villin-related proteins represent another
      family of cytoskeletal proteins, which has been identified as cross-reactive
      plant allergens. They may be used for the diagnosis and treatment of patients
      suffering from multivalent plant allergies.

PMID- 15978586
TI  - Negative regulation of hypoxia inducible factor-1alpha by necdin.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that mediates
      cellular and systemic homeostatic responses to reduce O2 availability, such as
      erythropoiesis, angiogenesis, and glycolysis. Using the yeast two-hybrid
      screening system, we found that the oxygen dependent degradation (ODD) domain of
      HIF-1alpha interacts with necdin, a growth suppressor. The interaction of necdin
      with HIF-1alpha was confirmed using coimmunoprecipitation with the overexpressed
      HIF-1alpha. Biological effect of necdin on HIF-1alpha showed that necdin reduces
      the transcriptional activity of HIF-1 under hypoxia. Moreover, necdin decreased
      the level of the HIF-1alpha protein, but not that of mRNA, implying a possibility
      of necdin-mediated HIF-1alpha degradation. Furthermore, necdin has an anti
      angiogenic activity in the tube formation assay and CAM assay, which might be due
      to the downregulation of HIF-1alpha. Collectively, these results suggest that
      necdin can be a novel negative regulator of HIF-1alpha stability via the direct
      interaction.

PMID- 15978585
TI  - fldA is an essential gene required in the 2-C-methyl-D-erythritol 4-phosphate
      pathway for isoprenoid biosynthesis.
AB  - Although flavodoxin I is indispensable for Escherichia coli growth, the exact
      pathway(s) where flavodoxin I is essential has not been identified. We performed
      transposon mutagenesis of the flavodoxin I gene, fldA, in an E. coli strain that
      expressed mevalonate pathway enzymes and that had a point mutation in the lytB
      gene of the MEP pathway resulting in the accumulation of (E)-4-hydroxy-3
      methylbutyl-2-enyl pyrophosphate (HMBPP). Disruption of fldA abrogated mevalonate
      independent growth and dramatically decreased HMBPP levels. The fldA- mutant grew
      with mevalonate indicating that the essential role of flavodoxin I under aerobic
      conditions is in the MEP pathway. Growth was restored by fldA complementation.
      Since GcpE (which synthesizes HMBPP) and LytB are iron-sulfur enzymes that
      require a reducing system for their activity, we propose that flavodoxin is
      essential for GcpE and possibly LytB activity. Thus, the essential role for
      flavodoxin I in E. coli is in the MEP pathway for isoprenoid biosynthesis.

PMID- 15978587
TI  - Drosophila RET contains an active tyrosine kinase and elicits neurotrophic
      activities in mammalian cells.
AB  - The RET receptor tyrosine kinase controls kidney organogenesis and development of
      subpopulations of enteric and sensory neurons in different vertebrate species,
      including humans, rodents, chicken and zebrafish. RET is activated by binding to
      a ligand complex formed by a member of the glial cell line-derived neurotrophic
      factor (GDNF) family of neurotrophic factors bound to its cognate GFRalpha GPI
      linked co-receptor. Despite the absence of GDNF or GFRalpha molecules in the
      Drosophila genome, a RET orthologue (dRET) has recently been described in this
      organism and shown to be expressed in subpopulations of cells of the excretory,
      digestive and nervous systems, thus resembling the expression pattern of RET in
      vertebrates. In this study, we report on the initial biochemical and functional
      characterization of the dRET protein in cell culture systems. Full-length dRET
      could be produced in mammalian and insect cells. Similar to its human counterpart
      (hRET), overexpression of dRET resulted in its ligand-independent tyrosine
      phosphorylation, indicating that it bears an active tyrosine kinase. Unlike hRET,
      however, the extracellular domain of dRET was unable to interact with mammalian
      GDNF and GFRalpha1. Self association between dRET molecules could neither be
      detected, indicating that dRET is incapable of mediating cell adhesion by
      homophilic interactions. A chimeric molecule comprising the extracellular domain
      of hRET and the kinase domain of dRET was constructed and used to probe ligand
      mediated downstream activities of the dRET kinase in PC12 cells. GDNF stimulation
      of cells transfected with the hRET/dRET chimera resulted in neurite outgrowth
      comparable to that obtained after transfection of wild-type hRET. These results
      indicate significant conservation between the biological effects elicited by the
      human and Drosophila RET kinases, and suggest functions for dRET in neuronal
      differentiation in the fly.

PMID- 15978588
TI  - Characterization of a functional P2X(7)-like receptor in cerebellar granule
      neurons from P2X(7) knockout mice.
AB  - The presence of ionotropic P2X(7) receptor has been studied in mice brain from
      wild type and P2X(7) receptor knockout animals. Western blot and
      immunocytochemical assays show the presence of a protein containing the P2X(7)
      immunogenic epitopes in the brain of knockout model. Reverse transcriptase
      polymerase chain reaction experiments demonstrate the absence of the disrupted
      sequence, but other sequences of P2X(7) specific mRNA expression have been
      detected. Functional calcium imaging experiments in cultured granule neurons from
      P2X(7) knockout cerebella show the existence of a functional P2X(7)-like receptor
      that keeps some of the properties of the genuine receptor.

PMID- 15978589
TI  - Hsp27-2D-gel electrophoresis is a diagnostic tool to differentiate primary
      desminopathies from myofibrillar myopathies.
AB  - Small heat shock proteins prevent abnormal protein folding and accumulation. We
      analyzed the expression of hsp27 and alphaB-crystallin in skeletal muscle
      specimens of patients with desminopathies, plectinopathies, myotilinopathy, and
      other myofibrillar myopathies by means of differential centrifugation, 2D-gel
      electrophoresis, Western blotting, and mass spectrometry. Hsp27-P82 and -P15 as
      well as alphaB-crystallin-P59 and -P45 are the major serine phosphorylation
      isoforms in normal and diseased human skeletal muscle. 2D-gel-electrophoresis
      revealed spots of hsp27 in a range of pH 5.3-6.4 in samples of all skeletal
      muscle specimens, except for the seven desminopathies. They indicated a shift of
      the main hsp27-spot to alkaline pH degrees, which may help to differentiate
      primary desminopathies from other myopathies with structural pathology of the
      desmin cytoskeleton.

PMID- 15978590
TI  - Ceramide-1-phosphate promotes cell survival through activation of the
      phosphatidylinositol 3-kinase/protein kinase B pathway.
AB  - In this report, we show for the first time that ceramide-1-phosphate (C1P)
      stimulates the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB)
      pathway, which is a major mechanism whereby growth factors promote cell survival.
      Also, C1P induced IkappaB phosphorylation, and enhanced the DNA binding activity
      of the transcription factor NF-kappaB. Apoptotic macrophages showed a marked
      reduction of Bcl-X(L) levels, and this was prevented by C1P. These findings
      suggest that C1P blocks apoptosis, at least in part, by stimulating the PI3
      K/PKB/NF-kappaB pathway and maintaining the production of antiapoptotic Bcl-X(L).
      Based on these and our previous observations, we propose a working model for C1P
      in which inhibition of acid sphingomyelinase and the subsequent decrease in
      ceramide levels would allow cell signaling through stimulation of the PI3-K/PKB
      pathway to promote cell survival.

PMID- 15978591
TI  - Direct interaction between metastasis-associated protein 1 and endophilin 3.
AB  - The yeast two-hybrid system was used to search for partners of mouse metastasis
      associated protein 1 (Mta1). Screening of a cDNA library prepared from mouse
      embryo yielded positive clones coding for endophilin 3. The site of interaction
      was suggested to be the SH-3-binding domain of Mta1 and SH-3 domain of endophilin
      3. This interaction was confirmed by GST pull-down assay in vitro and
      immunoprecipitation in vivo. The Mta1 and endophilin 3 transcripts were highly
      expressed in testis and brain. But, Mta1 localized mainly in nucleus and to a
      lesser extent in cytoplasm while endophilin 3 localized mainly in cytoplasm. If
      Mta1 functions in cytoplasm, it might be involved in the regulation of
      endocytosis mediated by endophilin 3.

PMID- 15978592
TI  - Functional characterization of neostatins, the MMP-derived, enzymatic cleavage
      products of type XVIII collagen.
AB  - Several anti-angiogenic factors are derived from proteolytic processing of large
      molecules including endostatin from type XVIII collagen and angiostatin from
      plasminogen. In previous studies we showed that neostatin-7, the C-terminal 28kDa
      endostatin-spanning proteolytic fragment, is generated from the proteolytic
      action of matrix metalloproteinase matrilysin (MMP)-7 on type XVIII collagen.
      Now, we report a second member of the neostatin family of proteins, neostatin-14.
      Given the small quantities of neostatin-7 and -14 generated by the breakdown of
      naturally occurring collagen XVIII (using MMP-7 and -14, respectively), we used
      two other approaches to characterize the anti-angiogenic properties of these
      molecules: murine recombinant neostatin in vitro, and gene therapy. We
      demonstrate that murine recombinant neostatin-7 inhibits calf pulmonary artery
      endothelial cell proliferation and that microinjection of neostatin-7 and
      neostatin-14 naked DNA into the corneal stroma of mice results in significant
      reduction of basic fibroblast growth factor-induced corneal neovascularization.
      These results provide supportive evidence of the possible anti-angiogenic effect
      of neostatins.

PMID- 15978593
TI  - Effects of social status, age, and season on androgen and cortisol levels in wild
      male golden lion tamarins (Leontopithecus rosalia).
AB  - This study examines factors affecting androgen and cortisol levels in wild, male
      golden lion tamarins (Leontopithecus rosalia). Golden lion tamarins are a
      cooperatively breeding species in which groups often contain two potentially
      breeding males. Brothers frequently emigrate together and develop a clear
      dominance hierarchy, but interactions between them are primarily affiliative.
      Duos in which the males are not related are less stable. In addition,
      reproductive skew theory predicts that dominant males will be less likely to
      share reproduction with related subordinates. As such, we predicted that both
      androgens and cortisol would be higher in subordinate males unrelated to the
      dominant male. We also predicted that androgens in breeding males would be higher
      during the mating season than the birth/infant care season, as per Wingfield's
      "challenge hypothesis" (1990). Fecal samples were collected from 24 males in 14
      social groups and assayed by enzyme immunoassay. Androgen levels were higher in
      breeding males during the mating season, thus supporting the challenge
      hypothesis. However, while subordinate males unrelated to the dominant male had
      significantly lower androgens than any other group, cortisol levels were not
      correspondingly higher. These results suggest that unrelated subordinate males
      show measurable reproductive suppression and may use strategies such as
      infantilization to avert aggression from dominant males.

PMID- 15978594
TI  - Right atrium tear as cause of death after blunt chest trauma.

PMID- 15978595
TI  - Hong Kong nursing students' perception of the clinical environment: a
      questionnaire survey.
AB  - Clinical practice is a vital component of the nursing curriculum yet it takes
      place in a complex social context. This survey examined Hong Kong nursing
      students' perception of the social climate of the clinical learning environment.
      The targeted subjects were all Years 2-4 pre-registration nursing students at the
      school of nursing of a major University in Hong Kong. Participants were invited
      to complete the two versions, the actual and preferred forms, of the Clinical
      Learning Environment Inventory following the completion of their clinical field
      placement. Two hundred and eighty one actual forms and 243 preferred forms were
      returned. SPPS version 11 was employed to analyse the data using descriptive and
      inferential statistics. It was found that there were significant differences
      between students' perceptions of the actual clinical learning environment and the
      ideal clinical learning environment they desired. The study highlights the need
      for a supportive clinical learning environment which is of paramount importance
      in securing the required teaching and learning process for students on clinical
      practice.

PMID- 15978596
TI  - Where does responsibility end?

PMID- 15978597
TI  - Dense granules: are they key organelles to help understand the parasitophorous
      vacuole of all apicomplexa parasites?
AB  - Together with micronemes and rhoptries, dense granules are specialised secretory
      organelles of Apicomplexa parasites. Among Apicomplexa, Plasmodium represents a
      model of parasites propagated by way of an insect vector, whereas Toxoplasma is a
      model of food borne protozoa forming cysts. Through comparison of both models,
      this review summarises data accumulated over recent years on alternative
      strategies chosen by these parasites to develop within a parasitophorous vacuole
      and explores the role of dense granules in this process. One of the
      characteristics of the Plasmodium erythrocyte stages is to export numerous
      parasite proteins into both the host cell cytoplasm and/or plasma membrane via
      the vacuole used as a step trafficking compartment. Whether this feature can be
      correlated to few storage granules and a restricted number of dense granule
      proteins, is not yet clear. By contrast, the Toxoplasma developing vacuole is
      decorated by abundantly expressed dense granule proteins and is characterised by
      a network of membranous nanotubes. Although the exact function of most of these
      proteins remains currently unknown, recent data suggest that some of these dense
      granule proteins could be involved in building the intravacuolar membranous
      network. Conserved expression of the Toxoplasma dense granule proteins throughout
      most of the parasite stages suggests that they could also be key elements of the
      cyst formation.

PMID- 15978598
TI  - Glenohumeral elevation-dependent influence of anterior glenohumeral capsular
      lesions on passive axial humeral rotation.
AB  - The purpose of this study was to assess the effect of standardized anterior
      glenohumeral capsular lesions on axial humeral rotation in a full arc of
      glenohumeral elevation. Using a testing apparatus, the range of internal and
      external humeral rotation was assessed in an arc of glenohumeral elevation in the
      scapular plane with steps of 15 degrees in six isolated shoulder joint specimens.
      Cutting of the glenohumeral joint capsule 1 cm laterally from, and parallel to
      the glenoid rim was performed in seven steps of 1 cm till the anterior capsule
      was cut. Capsular lesions were made in three ways: from inferior, from superior
      and from the middle of the capsule. Anterior capsular lesions resulted in
      significant increase of external humeral rotation. This occurred particularly at
      15-60 degrees glenohumeral elevation. Lesions of the inferior part of the capsule
      mainly increased external rotation at 30-60 degrees glenohumeral elevation,
      lesions of the superior part mainly in lower elevation angles and lesions of the
      middle more gradually in the range till 60 degrees of glenohumeral elevation.
      Cutting of the anterior glenohumeral capsule barely increased passive axial
      humeral rotation at elevation angles over 60 degrees. Above 60 degrees
      glenohumeral elevation, tightening of the inferior posterior glenohumeral joint
      capsule prevented both internal and, increasingly, external humeral rotation.
      From these observations it is concluded that increased external rotation
      correlates with progressive anterior capsular lesions, mainly below 60 degrees
      glenohumeral elevation. To assess anterior glenohumeral capsular lesions in
      patients, axial humeral rotation tests should probably not exceed 60 degrees
      glenohumeral elevation, i.e. 90 degrees thoracohumeral elevation.

PMID- 15978599
TI  - An extended modeling of the micropipette aspiration experiment for the
      characterization of the Young's modulus and Poisson's ratio of adherent thin
      biological samples: numerical and experimental studies.
AB  - The micropipette aspiration (MA) experiment remains a quite widely used
      micromanipulation technique for quantifying the elastic modulus of cells and,
      less frequently, of other biological samples. However, moduli estimations derived
      from MA experiments are only valid if the probed sample is non-adherent to the
      rigid substrate. This study extends this standard formulation by taking into
      account the influence of the sample adhesion. Using a finite element analysis of
      the sample aspiration into the micropipette, we derived a new expression of the
      aspirated length for linear elastic materials. Our results establish that (i)
      below a critical value, the thickness h of the probed sample must be considered
      to get an accurate value of its Young's modulus (ii) this critical value depends
      both on the Poisson's ratio and on the sample adhesivity. Additionally, we
      propose a novel method which allows the computation of the intrinsic Young's
      modulus of the adherent probed sample from its measured apparent elasticity
      modulus. Thanks to the set of computational graphs we derived from our
      theoretical analysis, we successfully validate this method by experiments
      performed on polyacrylamide gels. Interestingly, the original procedure we
      proposed allows a simultaneous quantification of the Young's modulus and of the
      Poisson's ratio of the adherent gel. Thus, our revisited analysis of MA
      experiments extends the application domain of this technique, while contributing
      to decrease the dispersion of elastic modulus values obtained by this method.

PMID- 15978600
TI  - Attractive interactions between like-charged colloidal particles at the air/water
      interface.
AB  - In the past few years, measurements of the pair interaction potential have shown
      evidence of micrometer-range attractive interactions between colloidal particles
      trapped between glass plates. In these experiments it is believed that the glass
      walls play an important role in the observed attractions. Colloidal particles
      trapped at the air/water interface show the formation of different 2-D colloidal
      patterns such as foams, clusters, and chains, whose formation has been taken as
      evidence of micrometer-range attractive interaction. Here, we present
      measurements of the pair interaction potential between 0.5-microm colloidal
      particles at the air/water interface. Indeed, the pair potential shows an
      attractive secondary minimum at about 1.9sigma, where sigma is the particle's
      diameter. Surprisingly, the position and depth of the secondary well are similar
      to those found in colloidal systems trapped between glass plates. However, we do
      not have a clear explanation on the origin of the attractive component of the
      interaction potential.

PMID- 15978601
TI  - Ion-specific repulsive interactions in colloidal silica dispersions evidenced
      through osmotic compression measurements and implication in frontal
      ultrafiltration experiments.
AB  - Comparative osmotic compression experiments were performed on colloidal silica
      dispersions in the presence of various chloride salts at the same 0.01 M
      concentration with different counterions and highlighted the influence of ionic
      specificity on the resistance to water removal. These results were complemented
      with frontal ultrafiltration measurements that demonstrate modulation of the
      permeate flux according to the salt used.

PMID- 15978602
TI  - Collagen adsorption and structure on polymer surfaces observed by atomic force
      microscopy.
AB  - The structure and adsorption patterns of type I and type III collagen were imaged
      on various polymer substrates with atomic force microscopy. Type I collagen had
      higher adsorption on polystyrene than on a series of polymethacrylates and formed
      a network of tightly, interwoven strands. Upon adsorption to different
      polymethacrylates, with varying side chain lengths, the collagen molecules formed
      long, branching fibrils. Types I and III collagen had different adsorption
      patterns, in some cases, on the identical substrate material. For example,
      instead of forming a tightly packed network, type III forms long, branching
      fibers on the polystyrene surface. On other materials, such as poly(n-butyl
      methacrylate), the two types of collagen showed similar adsorption pattern and
      structure. Adsorbed collagen was also imaged on various blends of polystyrene and
      polymethacrylates to determine how the polymer surface chemical structure and
      surface topography mediates protein adsorption.

PMID- 15978603
TI  - The effect of structural variation of alcohols on water solubilization in
      nonionic microemulsions 2. Branched alcohols as solubilization modifiers: results
      and interpretation.
AB  - In this second part of a paper dealing with the effect of branched alcohols on
      solubilization, an attempt has been made to provide explanations of experimental
      data related mostly to the system Brij 97/branched alcohol + dodecane = 1:1 (by
      weight)/water at 27+/-0.2 degrees C. Applying the Hou-Shah mechanism it was shown
      that for many C4-C6 branched alcohol isomers having one methyl branch,
      solubilization behavior is readily interpreted by assuming control of the
      critical radius, R(c). Two parameters, both included in the definition of the
      branching factor, F(b) (which was treated in the first part of the paper), were
      also used to analyze solubilization data. The first, l(i), is defined as the
      distance from the free end of the alcohol molecule to the methyl branch. The
      second, d, is virtually N(A), the chain length of the alcohol. When l(i)>3, the
      solubilization becomes dominated by the natural radius of curvature, R0. Also, we
      have suggested that for R(c)-control, solubilization will be enhanced in direct
      proportion to the distance d-l(i), whereas for R0-control, solubilization will
      increase with decreasing d-l(i). The validity of our assumptions was demonstrated
      in many cases. Some examples of the more complicated case of double branching
      (two methyl groups along the alcohol chain) were also analyzed.

PMID- 15978604
TI  - Visco-elastic and adhesive properties of adsorbed polyelectrolyte multilayers
      determined in situ with QCM-D and AFM measurements.
AB  - The build-up of multilayers constructed from polyallylamine hydrochloride (PAH)
      and polyacrylic acid (PAA) under different pH conditions was continuously
      monitored using the quartz crystal microbalance with dissipation. The adsorbed
      amount of polymer as well as the amount of coupled water was determined.
      Furthermore, from dissipation measurements, it was possible to determine the
      visco-elastic properties of the adsorbed multilayer. These properties were highly
      dependent on the polyelectrolyte present in the outermost layer. The multilayer
      was far more rigid and elastic with PAA as the outermost layer. Furthermore, a
      link has been established between the conformability or rigidity of a multilayer
      covered surface and the adhesion between such surfaces. Adhesion measurements
      using the atomic force microscope showed a greater pull-off force when the more
      viscous PAH was present in the outermost layer.

PMID- 15978605
TI  - Self-assembly of 1,4-phenylene diisocyanide and terephthalic acid on Ni, Cu and
      Pt.
AB  - This paper compares the adsorption behavior of 1,4-phenylene diisocyanide (PDI)
      and terephthalic acid (TA) on Ni, Cu and Pt surfaces. Following competitive
      adsorption from two-component equimolar solutions of PDI and TA, chemical
      analysis by XPS confirmed the preferential adsorption of PDI over TA on Ni and
      Cu. The ability to form "chemically sticky" surfaces on Ni, Cu and Pt surfaces by
      self-assembly into organized organic thin films (OOTFs) was also investigated. PM
      IRRAS analysis revealed a tendency for PDI to bond in a terminal fashion through
      one isocyanide group, on both Ni and Cu. In contrast, PDI adsorbed in a flat
      configuration on Pt. Chemically sticky OOTFs have potential for utilization as
      coupling agents to achieve a high cross-link density and enhance stress transfer
      between the nanoclusters and the organic matrix molecules in metal-nanocluster
      filled polymer matrix nanocomposites. The results of this work indicate that 1,4
      phenylene diisocyanide is a suitable choice as a coupling agent for metal
      nanoclusters of Ni and Cu.

PMID- 15978606
TI  - On derivatives of surface charge curves of minerals.
AB  - Surface titrations of minerals in aqueous electrolyte solutions are used as
      building blocks for surface complexation modelling. However, these potentiometric
      data may contain less model relevant information than previously and presently
      assumed. In the literature, derivative analyses have been applied to experimental
      surface charge versus pH curves and four or more pK values were extracted for
      goethite or aluminium oxide. Derivative analysis of specific surface charge
      versus pH curves calculated for various published model variants for goethite
      shows that not more than the net-zero proton surface charge condition can be
      extracted from computer generated data. Generated data can be produced in density
      and precision superior to experimental data, but yield only relatively little
      output from such derivative analysis compared to what has previously been
      extracted from derivatives of experimental data. For the generated goethite data
      and for all model variants only the point of zero could be extracted. For the
      various goethite model variants tested a nearly symmetrical peak appeared at the
      point of zero charge in the derivative curve. A different pattern could be
      obtained for generic models, for which two sites with unequal sites densities and
      different pK values were assumed. Variation of these parameters could result in
      derivatives of the charging curves with two maxima or one maximum and a broad
      tailing. In the literature, curves with features nearly identical to these
      generated curves have been interpreted by up to four pK values (i.e., four
      different sites within a 1-pK model). It is concluded that the interpretation of
      the generated data is in all cases hampered by the overwhelming electrostatic
      contributions to the free energy of proton ad/desorption. In no case except for
      the one-site 1-pK model was it possible to extract the input pK value(s) from the
      derivatives. Plausible explanations for the discrepancy between generated data
      and published experimental data are discussed.

PMID- 15978607
TI  - Electrosorption of thiocyanate anions on active carbon felt electrode in dilute
      solution.
AB  - Adsorption and electrosorption of thiocyanate (SCN-) anions on active carbon felt
      electrodes were measured by UV spectroscopy and cyclic voltammetry to provide
      more knowledge of the application of electrosorption on high-area carbon material
      in industrial waste water purification. Positive polarization caused increased
      adsorption of SCN-. SCN- showed the highest electrosorption capacity at about pH
      3. Reversible electrosorption of SCN- to different extents was observed by
      changing the direction of polarization currents, which is possibly accompanied by
      the accessible surface area of C-felt being increased by positive polarization
      and electrochemical oxidation of SCN-. The enhanced capacity for adsorption by
      positive polarization will improve reuse of active carbon felt.

PMID- 15978608
TI  - Perception of the voicing distinction in speech produced during simultaneous
      communication.
AB  - This study investigated the perception of voice onset time (VOT) in speech
      produced during simultaneous communication (SC). Four normally hearing,
      experienced sign language users were recorded under SC and speech alone (SA)
      conditions speaking stimulus words with voiced and voiceless initial consonants
      embedded in a sentence. Twelve hearing-impaired listeners participated, with
      three of them randomly assigned to audit the speech sample provided by each one
      of the four speakers under the SC and SA conditions. In addition, 24 normal
      hearing listeners were randomly assigned to audit the speech samples produced by
      the four speakers under the SC and SA conditions, three listeners in noise and
      three listeners in filtered listening conditions for each of the four speakers.
      Although results indicated longer sentence durations for SC than SA, results
      showed no difference in the perception of the voicing distinction for speech
      produced during SC versus speech produced during SA under either the noise or
      filtered listening condition, or any difference in perception for the hearing
      impaired listeners. This conclusion is consistent with previous research
      indicating that temporal alterations produced by SC do not produce degradation of
      temporal or spectral cues in speech or disruption of the perception of specific
      English phoneme segments. LEARNING OUTCOMES: As a result of this activity, the
      participant will be able to: (1) describe simultaneous communication; (2) explain
      the role of simultaneous communication in communication with persons who are
      hearing-impaired; (3) discuss methods of measuring perception of voice onset time
      with hearing-impaired listeners and with hearing listeners under filtered and
      noise conditions; and (4) specify the ability of listeners to perceive the
      voicing distinction in speech produced during simultaneous communication.

PMID- 15978609
TI  - Allopurinol and heart failure: a new use for an old drug?

PMID- 15978610
TI  - A role for mineralocorticoid receptor blockade in the prevention of apoptosis.

PMID- 15978611
TI  - Activation of IKKbeta by glucose is necessary and sufficient to impair insulin
      signaling and nitric oxide production in endothelial cells.
AB  - Hyperglycemic impairment of nitric oxide (NO) production by endothelial cells is
      implicated in the effect of diabetes to increase cardiovascular disease risk, but
      the molecular basis for this effect is unknown. In skeletal muscle, diabetes
      induces activation of inhibitor kappaB kinase (IKKbeta), a key cellular mediator
      of the response to inflammatory stimuli, and this impairs insulin signal
      transduction via the insulin receptor substrate-phosphatidylinositol 3-OH kinase
      (IRS-1/PI3-kinase) pathway. Since activation of endothelial nitric oxide synthase
      (eNOS) is dependent on IRS-1/PI3-kinase signaling, we hypothesized that
      activation of IKKbeta may contribute to the effect of glucose to impair NO
      production. Here, we show that exposure of bovine aortic endothelial cells to
      high glucose (25 mM) for 24 h impaired insulin-mediated tyrosine phosphorylation
      of IRS-1, serine phosphorylation of Akt, activation of eNOS, and production of
      NO. High glucose treatment also activated IKKbeta, and pretreatment with aspirin,
      a pharmacological inhibitor of IKKbeta, prevented both glucose-induced IKKbeta
      activation and the effect of high glucose to impair insulin-mediated NO
      production. These adverse responses to glucose were also blocked by selective
      inhibition of IKKbeta signaling via overexpression of a kinase-inactive form of
      the enzyme. Conversely, overexpression of wild-type IKKbeta recapitulated the
      deleterious effect of high glucose on insulin-mediated activation of eNOS. These
      data demonstrate that activation of IKKbeta plays a critical and novel role to
      mediate the deleterious effects of high glucose on endothelial cell function.

PMID- 15978612
TI  - Young MLP deficient mice show diastolic dysfunction before the onset of dilated
      cardiomyopathy.
AB  - Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently
      leads to dilated cardiomyopathy (DCM) after one or more months. However, next to
      nothing is known at present about the mechanisms of this process. We investigated
      whether diastolic performance including passive mechanics and systolic behavior
      are altered in 2-week-old MLP knockout (MLPKO) mice, in which heart size,
      fractional shortening and ejection fraction are still normal. Right ventricular
      trabeculae were isolated from 2-week-old MLPKO and wildtype mice and placed in an
      apparatus that allowed force measurements and sarcomere length measurements using
      laser diffraction. During a twitch from the unloaded state at 1 Hz, MLPKO muscles
      relengthened to slack length more slowly than controls, although the
      corresponding force relaxation time was unchanged. Active developed stress at a
      diastolic sarcomere length of 2.00 microm was preserved in MLPKO trabeculae over
      a wide range of pacing frequencies. Force relaxation under the same conditions
      was consistently prolonged compared with wildtype controls, whereas time to peak
      and maximum rate of force generation were not significantly altered. Ca2+ content
      of the sarcoplasmic reticulum (SR) and the quantities of Ca2+ handling proteins
      were similar in both genotypes. In summary, young MLPKO mice revealed substantial
      alterations in passive myocardial properties and relaxation time, but not in most
      systolic characteristics. These results indicate that the progression to heart
      failure in the MLPKO model may be driven by diastolic myocardial dysfunction and
      abnormal passive properties rather than systolic dysfunction.

PMID- 15978613
TI  - The fall in creatine levels and creatine kinase isozyme changes in the failing
      heart are reversible: complex post-transcriptional regulation of the components
      of the CK system.
AB  - Decreases in total creatine kinase (CK) activity and creatine [Cr] combine to
      limit the capacity of the failing heart to rapidly re-synthesize ATP (energy
      reserve). If the loss in energy reserve could be reversed, cardiac contractile
      reserve may be improved. Here we test whether these changes are reversible during
      recovery from heart failure. Left ventricular (LV) contractile function was
      measured in chronically instrumented conscious dogs with heart failure (CHF)
      induced by cardiac pacing for 3-4 weeks, and after recovery from heart failure
      (Recovery) (unpaced) for 5-6 weeks. LV contractile function and contractile
      reserve were depressed in CHF but returned to control in Recovery. CK capacity
      fell by 55% in CHF due to decreases in [Cr] (-39%) and CK activity (-25%), but
      was fully restored in Recovery. CK-B isozyme activity, protein (Western) and mRNA
      levels (real time PCR), respectively, were higher by 2-, 5.4- and 11-fold in CHF
      and higher by 3-, 2- and 2-fold in Recovery. CK-MM activity was decreased (-30%)
      in CHF but returned to normal levels during Recovery; CK-M protein was 30% lower
      in both CHF and Recovery even though there were no changes in mRNA levels. A
      similar pattern was found for mitochondrial CK (sMtCK). Deceases in CK activity
      and [Cr] in CHF are reversible. Decreases in CK-MM and sMtCK activities, but not
      the increases in CK-BB and CK-MB, also reversed. Neither the changes in protein
      nor mRNA levels for CK-B and CK-M correlated to their activities, suggesting that
      CK is under complex post-transcriptional regulation.

PMID- 15978614
TI  - SIH--a novel lipophilic iron chelator--protects H9c2 cardiomyoblasts from
      oxidative stress-induced mitochondrial injury and cell death.
AB  - Recent evidence suggests that oxidative stress is a common denominator in many
      aspects of cardiovascular pathogenesis. Free cellular iron plays a crucial
      catalytic role in the formation of highly toxic hydroxyl radicals, and thereby it
      may aggravate the contribution of oxidative stress to cardiovascular disease.
      Therefore, iron chelation may be an effective therapeutic approach, but the
      progress in this area is hindered by the lack of effective agents. In this study,
      using the rat heart myoblast-derived cell line H9c2, we aimed to investigate
      whether the novel lipophilic iron chelator salicylaldehyde isonicotinoyl
      hydrazone (SIH) protects the cells against hydrogen peroxide (H2O2)-induced
      cytotoxicity. Exposure of cells to 100 micromol/l H2O2 has within 4 h induced a
      complete dissipation of their mitochondrial membrane potential (DeltaPsim). Co
      treatment with SIH dose-dependently reduced (EC50=0.8 micromol/l) or even
      completely abolished (3 micromol/l) this collapse. Furthermore, the latter SIH
      concentration was capable to fully prevent alterations in cell morphology, and
      inhibited both apoptosis (annexin-V staining, nuclear chromatin shrinkage, TUNEL
      positivity) and necrosis (propidium iodide staining), even 24 h after the H2O2
      exposure. In comparison, deferoxamin (a commercially available hydrophilic iron
      chelator used in clinical practice and most previous studies) was cytoprotective
      only at three-order higher and clinically unachievable concentrations (EC50=1300
      micromol/l). Thus, in this study, we present iron chelation as a very powerful
      tool by which oxidative stress-induced myocardial damage can be prevented.

PMID- 15978615
TI  - Mycophenolate mofetil prevents the development of experimental autoimmune
      myocarditis.
AB  - Experimental autoimmune myocarditis (EAM) is characterized by the appearance of
      multinucleated giant cells. EAM leads to severe myocardial damage and is a useful
      model of human giant cell myocarditis. We investigated whether mycophenolate
      mofetil (MMF), which is a potent immunosuppressant, prevents the development of
      myocarditis in a rat EAM model, and focused on the role of osteopontin (OPN) in
      the pathogenesis of this disorder. Adult Lewis rats were immunized with porcine
      cardiac myosin to establish EAM. The early MMF treatment completely prevented the
      development of EAM, and the late MMF treatment was also effective even against
      established EAM. Echocardiogram demonstrated that left ventricular function was
      also improved by the treatment with MMF. Real-time RT-PCR analysis showed that
      both early and late MMF treatments significantly inhibited myocarditis-induced
      OPN mRNA expression in the heart. Immunohistochemistry revealed that OPN
      expression was prominent in the myocardium on day 14, whereas expression was
      observed in the infiltrated macrophages on day 21. Mycophenolic acid (MPA) did
      inhibit agonist-induced OPN expression in cultured cardiomyocytes. These results
      show the therapeutic potential of MMF for autoimmune myocarditis and provide new
      insights into the pathogenesis of this disease.

PMID- 15978616
TI  - Proteomic identification of M. tuberculosis protein kinase substrates: PknB
      recruits GarA, a FHA domain-containing protein, through activation loop-mediated
      interactions.
AB  - Genes for functional Ser/Thr protein kinases (STPKs) are ubiquitous in
      prokaryotic genomes, but little is known about their physiological substrates and
      their actual involvement in bacterial signal transduction pathways. We report
      here the identification of GarA (Rv1827), a Forkhead-associated (FHA) domain
      containing protein, as a putative physiological substrate of PknB, an essential
      Ser/Thr protein kinase from Mycobacterium tuberculosis. Using a global proteomic
      approach, GarA was found to be the best detectable substrate of the PknB
      catalytic domain in non-denatured whole-cell protein extracts from M.
      tuberculosis and the saprophyte Mycobacterium smegmatis. Enzymological and
      binding studies of the recombinant proteins demonstrate that docking interactions
      between the activation loop of PknB and the C-terminal FHA domain of GarA are
      required to enable efficient phosphorylation at a single N-terminal threonine
      residue, Thr22, of the substrate. The predicted amino acid sequence of the garA
      gene, including both the N-terminal phosphorylation motif and the FHA domain, is
      strongly conserved in mycobacteria and other related actinomycetes, suggesting a
      functional role of GarA in putative STPK-mediated signal transduction pathways.
      The ensuing model of PknB-GarA interactions suggests a substrate recruitment
      mechanism that might apply to other mycobacterial kinases bearing multiple
      phosphorylation sites in their activation loops.

PMID- 15978617
TI  - Crystal structure of the ENT domain of human EMSY.
AB  - EMSY is a recently discovered gene encoding a BRCA2-associated protein and is
      amplified in some sporadic breast and ovarian cancers. The EMSY sequence contains
      no known domain except for a conserved approximately 100 residue segment at the N
      terminus. This so-called ENT domain is unique in the human genome, although
      multiple copies are found in Arabidopsis proteins containing members of the Royal
      family of chromatin remodelling domains. Here, we report the crystal structure of
      the ENT domain of EMSY, consisting of a unique arrangement of five alpha-helices
      that fold into a helical bundle arrangement. The fold shares regions of
      structural homology with the DNA-binding domain of homeodomain proteins. The ENT
      domain forms a homodimer via the anti-parallel packing of the extended N-terminal
      alpha-helix of each molecule. It is stabilized mainly by hydrophobic residues at
      the dimer interface and has a dissociation constant in the low micromolar range.
      The dimerisation of EMSY mediated by the ENT domain could provide flexibility for
      it to bind two or more different substrates simultaneously.

PMID- 15978618
TI  - Remodeling of the sigma70 subunit non-template DNA strand contacts during the
      final step of transcription initiation.
AB  - Transcription initiation in bacteria requires melting of approximately 13 bp of
      promoter DNA. The mechanism of the melting process is not fully understood.
      Escherichia coli RNA polymerase bearing a deletion of the beta subunit lobe I
      (amino acid residues 186-433) initiates melting of the -10 promoter element but
      cannot propagate the melting downstream, towards the transcription initiation
      start site (+1). However, in the presence of nucleotides, stable downstream
      melting is induced. Here, we studied lacUV5 promoter complexes formed by the
      mutant enzyme by cross-linking RNA polymerase subunits to single-stranded DNA in
      the transcription bubble. In the absence of NTPs, a contact between the sigma70
      subunit and the non-template strand of the -10 promoter element was detected.
      This contact disappeared in the presence of NTPs. Instead, a new sigma70-DNA
      contact as well as stable beta' and beta subunit contacts with the non-template
      DNA downstream of the -10 promoter element were established. In terms of the two
      step (upstream initiation/downstream propagation) model of promoter melting, our
      data suggest that beta lobe I induces the propagation of promoter melting by
      directing downstream promoter DNA duplex towards the downstream DNA-binding
      channel (beta' clamp). Establishment of downstream contacts leads to remodeling
      of upstream interactions between sigma70 and the -10 promoter element that might
      facilitate promoter escape and sigma release.

PMID- 15978619
TI  - Armadillo: domain boundary prediction by amino acid composition.
AB  - The identification and annotation of protein domains provides a critical step in
      the accurate determination of molecular function. Both computational and
      experimental methods of protein structure determination may be deterred by large
      multi-domain proteins or flexible linker regions. Knowledge of domains and their
      boundaries may reduce the experimental cost of protein structure determination by
      allowing researchers to work on a set of smaller and possibly more successful
      alternatives. Current domain prediction methods often rely on sequence similarity
      to conserved domains and as such are poorly suited to detect domain structure in
      poorly conserved or orphan proteins. We present here a simple computational
      method to identify protein domain linkers and their boundaries from sequence
      information alone. Our domain predictor, Armadillo
      (http://armadillo.blueprint.org), uses any amino acid index to convert a protein
      sequence to a smoothed numeric profile from which domains and domain boundaries
      may be predicted. We derived an amino acid index called the domain linker
      propensity index (DLI) from the amino acid composition of domain linkers using a
      non-redundant structure dataset. The index indicates that Pro and Gly show a
      propensity for linker residues while small hydrophobic residues do not. Armadillo
      predicts domain linker boundaries from Z-score distributions and obtains 35%
      sensitivity with DLI in a two-domain, single-linker dataset (within +/-20
      residues from linker). The combination of DLI and an entropy-based amino acid
      index increases the overall Armadillo sensitivity to 56% for two domain proteins.
      Moreover, Armadillo achieves 37% sensitivity for multi-domain proteins,
      surpassing most other prediction methods. Armadillo provides a simple, but
      effective method by which prediction of domain boundaries can be obtained with
      reasonable sensitivity. Armadillo should prove to be a valuable tool for rapidly
      delineating protein domains in poorly conserved proteins or those with no
      sequence neighbors. As a first-line predictor, domain meta-predictors could yield
      improved results with Armadillo predictions.

PMID- 15978620
TI  - Crystal structure of the Vibrio cholerae cytolysin (VCC) pro-toxin and its
      assembly into a heptameric transmembrane pore.
AB  - Pathogenic Vibrio cholerae secrete V. cholerae cytolysin (VCC), an 80 kDa pro
      toxin that assembles into an oligomeric pore on target cell membranes following
      proteolytic cleavage and interaction with cell surface receptors. To gain insight
      into the activation and targeting activities of VCC, we solved the crystal
      structure of the pro-toxin at 2.3A by X-ray diffraction. The core cytolytic
      domain of VCC shares a fold similar to the staphylococcal pore-forming toxins,
      but in VCC an amino-terminal pro-domain and two carboxy-terminal lectin domains
      decorate the cytolytic domain. The pro-domain masks a protomer surface that
      likely participates in inter-protomer interactions in the cytolytic oligomer,
      thereby explaining why proteolytic cleavage and movement of the pro-domain is
      necessary for toxin activation. A single beta-octyl glucoside molecule outlines a
      possible receptor binding site on one lectin domain, and removal of this domain
      leads to a tenfold decrease in lytic activity toward rabbit erythrocytes. VCC
      activated by proteolytic cleavage assembles into an oligomeric species upon
      addition of soybean asolectin/cholesterol liposomes and this oligomer was
      purified in detergent micelles. Analytical ultracentrifugation and
      crystallographic analysis indicate that the resulting VCC oligomer is a heptamer.
      Taken together, these studies define the architecture of a pore forming toxin and
      associated lectin domains, confirm the stoichiometry of the assembled oligomer as
      heptameric, and suggest a common mechanism of assembly for staphylococcal and
      Vibrio cytolytic toxins.

PMID- 15978621
TI  - Adjunctive atomoxetine for residual fatigue in major depressive disorder.
AB  - OBJECTIVE: To assess the effectiveness and safety of atomoxetine as an adjunctive
      medication for residual fatigue in a naturalistic treatment setting. METHODS: A
      retrospective chart review was conducted to identify major depressive disorder
      (MDD) patients who had experienced significant symptom improvement (either
      partial response or remission) following treatment with conventional
      antidepressants but who were continuing to complain of fatigue. Fourteen such
      patients (42.2+/-13.4 years of age, five women, baseline HDRS 6.2+/-2.4) with a
      17-item Hamilton Depression Rating Scale (HDRS17)<11 who received adjunctive
      atomoxetine for fatigue were included in the report. Antidepressants augmented
      were the selective serotonin reuptake inhibitors (SSRIs) (n=11; 78.6%),
      mirtazapine (n=2, 14.3%), and amitriptyline (n=1, 7.1%). RESULTS: Twelve (85.7%)
      patients (nine remitters, three partial responders) received at least 4 weeks of
      atomoxetine treatment. The remaining two (partial responders) discontinued
      atomoxetine within 1-3 days due to increased anxiety. The brief fatigue inventory
      (BFI) and Clinical Global Impressions Scale (CGI) were administered when
      atomoxetine was first prescribed, and following 4-10 weeks of treatment (mean of
      5.4+/-1.8 weeks). There was a significant decrease in BFI scores (41.9+/-14.9
      versus 24.3+/-13.4, p=0.0015), and HDRS-17 scores (6.2+/-2.4 versus 3.5+/-2.8,
      p=0.0466), but not CGI-S scores (1.3+/-1.4-1.0+/-0.0, p=0.08) following treatment
      with atomoxetine. 5/12 (41.6%) patients had a 50% or greater decrease in BFI
      scores. All 12 patients were remitters at follow-up. The mean atomoxetine dose
      was 42.8+/-10.6 mg. Side effects included insomnia (n=6), increased anxiety
      (n=3), nausea (n=1) and dry mouth (n=1). CONCLUSIONS: Although preliminary, these
      results suggest a possible augmentation role for atomoxetine when used in
      conjunction with conventional antidepressants for residual fatigue in MDD.
      Prospective as well as controlled studies are necessary to further explore the
      role of atomoxetine augmentation in MDD.

PMID- 15978622
TI  - Heart rate variability predicts trauma patient outcome as early as 12 h:
      implications for military and civilian triage.
AB  - BACKGROUND: Our previous work demonstrated dense physiological data capture in
      the intensive care unit (ICU), defined a new vital sign Cardiac Volatility
      Related Dysfunction (CVRD) reflecting reduced heart rate variability, and
      demonstrated CVRD predicts death during the hospital stay adjusting for age and
      injury severity score (ISS). We hypothesized a more precise definition of
      variability in integer heart rate improves predictive power earlier in ICU stay,
      without adjusting for covariates. METHODS: Approximately 120 million integer
      heart rate (HR) data points were prospectively collected and archived from 1316
      trauma ICU patients, linked to outcome data, and de-identified. HR standard
      deviation was computed in each 5-min interval (HR(SD5)). HR(SD5) logistic
      regression identified ranges predictive of death. The study group was randomly
      divided. Integer heart rate variability (% time HR(SD5) in predictive
      distribution ranges) models were developed on the first set (N = 658) at 1, 2, 4,
      6, 8, 12, and 24 h after ICU admission, and validated on the second set (N =
      658). RESULTS: HR(SD5) is bimodal, predicts death at low (0.1-0.9 bpm) and
      survival at high (1.8-2.6 bpm) ranges. HRV predicts death as early as 12 h (ROC =
      0.67). HRV in a moving 1-h window is a simple graphic display technique.
      CONCLUSIONS: Dense physiological data capture allows calculation of HRV, which:
      1) Independently predicts hospital death in trauma patients at 12 h; 2) Shows
      early differences by mortality in groups of patients when viewed in a moving
      window; and 3) May have implications for military and civilian triage.

PMID- 15978623
TI  - Inhibition of intestinal transit by resuscitation-induced gut edema is reversed
      by L-NIL.
AB  - BACKGROUND: Post-resuscitation gut edema and associated gut dysfunction is a
      common and significant clinical problem that occurs after traumatic injury and
      shock. We have shown previously that gut edema without ischemia/reperfusion
      injury delays intestinal transit [1]. We hypothesized that gut edema increases
      expression of inducible nitric oxide synthase (iNOS) protein, and that selective
      iNOS inhibition using L-NIL reverses the delayed intestinal transit associated
      with gut edema. MATERIALS AND METHODS: One hour prior to laparotomy, rats were
      pretreated with 10 mg/kg body weight of intraperitoneal L-NIL or saline vehicle
      and underwent 80 ml/kg body weight of 0.9% saline + superior mesenteric venous
      pressure elevation (Edema) or sham surgery (Sham). A duodenal catheter was placed
      to allow injection of a fluorescent dye for the measurement of intestinal
      transit. At 6 h, the small bowel was divided and the mean geometric center (MGC)
      of fluorescent dye was measured to determine transit. Ileum was harvested for
      histological assessment of mucosal injury, evaluation of iNOS protein expression
      by Western blotting, and MPO activity. Tissue water was determined using the wet
      to-dry weight ratio to assess gut edema. Data are expressed as mean +/- SEM, n =
      3-6 and * = P <0.05 using ANOVA. RESULTS: Gut edema, expressed as increased wet
      to-dry ratio, was associated with decreased intestinal transit and elevated iNOS
      protein expression. Pretreatment with l-NIL improved intestinal transit and
      decreased expression of iNOS protein without decreasing intestinal tissue water
      compared to edema animals. There was no difference in mucosal injury or MPO
      activity among groups. CONCLUSION: Gut edema delays intestinal transit via an
      iNOS-mediated mechanism.

PMID- 15978624
TI  - Thermodynamic stability of ecosystems.
AB  - The stability of ecosystems during periods of stasis in their macro-evolutionary
      trajectory is studied from a non-equilibrium thermodynamic perspective.
      Individuals of the species are considered as units of entropy production and
      entropy exchange in an open thermodynamic system. Within the framework of the
      classical theory of irreversible thermodynamics, and under the condition of
      constant external constraints, such a system will naturally evolve toward a
      globally stable thermodynamic stationary state. It is thus suggested that the
      ecological steady state, or stasis, is a particular case of the thermodynamic
      stationary state, and that the evolution of community stability through natural
      selection is a manifestation of non-equilibrium thermodynamic directives.
      Furthermore, it is argued that punctuation of stasis leading to ecosystem
      succession, may be a manifestation of non-equilibrium "phase transitions" brought
      on by a change of external constraints through a thermodynamic critical point.

PMID- 15978625
TI  - Structuring of the genetic code took place at acidic pH.
AB  - I have observed that in multiple regression the number of codons specifying amino
      acids in the genetic code is positively correlated with the isoelectric point of
      amino acids and their molecular weight. Therefore basic amino acids are, on
      average, codified in the genetic code by a larger number of codons, which seems
      to imply that the genetic code originated in an acidic 'intracellular'
      environment. Moreover, I compare the proteins from Picrophilus torridus and
      Thermoplasma volcanium, which have different intracellular pH and I define the
      ranks of acidophily for the amino acids. A simple index of acidophily (AI), which
      can be easily obtained from acidophily ranks, can be associated to any protein
      and, therefore, can also be associated to the genetic code if the number of
      synonymous codons attributed to the amino acids in the code is assumed to be the
      frequency with which the amino acids appeared in ancestral proteins. Finally, the
      sampling of the variable AI among organisms having an intracellular pH less than
      or equal to 6.6 and those having a non-acidic intracellular pH leads to the
      conclusion that the value of the genetic code's AI is not typical of proteins of
      the latter organisms. As the genetic code's AI value is also statistically not
      different from that of proteins of the organisms having an acidic intracellular
      pH, this supports the hypothesis that the structuring of the genetic code took
      place in acidic pH conditions.

PMID- 15978626
TI  - Effects of amino acids from selenium-rich silkworm pupas on human hepatoma cells.
AB  - Selenium (Se) plays an important role in cancer-prevention. Silkworm pupas have
      been used as a Chinese traditional medicine since ancient time. In order to find
      effective carcinostatic agents, Se-rich amino acids were extracted from Ziyang
      silkworm pupas. The Se content of Ziyang pupas was measured to be 215 times
      higher than that of Luoyang normal ones, and the majority of Se was stored in
      proteins. Composition analysis showed that Se-rich amino acids from Ziyang pupas
      had higher amounts of selenomethionine, methionine, cystine, and tyrosine than
      normal amino acids from Luoyang pupas which were rich in amino acids containing
      alkyl side chains. When cultured with human hepatoma cells SMMC-7721, Se-rich
      amino acids at concentrations of 0.5, 1.5, and 2.5 micromol L(-1) Se
      significantly and dose-dependently inhibited cell viability, induced changes in
      cell morphology and cycle, and caused cell apoptosis. On the contrary, normal
      amino acids did not show any inhibitory effect on SMMC-7721 cells. Sodium
      selenite or selenomethionine at the same Se concentrations only slightly
      inhibited the hepatoma cells. Mechanism study showed that selenium-rich amino
      acids could increase the generation of intracellular reactive oxygen species
      (ROS) concentration-dependently. Antioxidant N-acetylcyteine partially inhibited
      the increase of ROS. Those results suggested that Se-rich amino acids were
      effective carcinostatic agents compared with sodium selenite and
      selenomethionine. The mechanism for their hepatoma-inhibitory effects was the
      induction of cellular apoptosis through ROS generation.

PMID- 15978627
TI  - Do inhalation general anesthetic drugs induce the neuronal release of endogenous
      opioid peptides?
AB  - The antagonism of some effects of inhalation general anesthetic agents by
      naloxone suggests that there may be an opioid component to anesthetic action.
      There is evidence that this opioid action component is due to neuronal release of
      endogenous opioid peptides. The strongest evidence is provided by studies that
      monitor changes in the concentration of opioid peptides in the perfused brain
      following inhalation of the anesthetic. Indirect or circumstantial evidence also
      comes from studies of anesthetic effects on regional brain levels of opioid
      peptides, antagonism of selected anesthetic effects by antisera to opioid
      peptides and anesthetic-induced changes radioligand binding to opioid receptors.
      It is likely that some inhalation general anesthetics (e.g., nitrous oxide) can
      induce neuronal release of opioid peptides and that this may contribute to
      certain components of general anesthesia (e.g., analgesia). More definitive
      studies utilizing in vivo microdialysis or autoradiography in selected areas of
      the brain during induction and successive states of general anesthesia have yet
      to be conducted.

PMID- 15978628
TI  - Antioxidant enzymes and lipid peroxides in children with cerebral palsy.
AB  - Impaired antioxidant mechanisms are unable to inactivate free radicals that may
      induce a number of pathophysiological processes and result in cell injury. Thus,
      any abnormality in antioxidant defense systems could affect neurodevelopmental
      processes and could have an important role in the etiology of cerebral palsy
      (CP). The plasma levels of lipid peroxidation as plasma levels of malondialdehyde
      (MDA), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx),
      and glutathione reductase (GR) in plasma and erythrocytes were investigated in 34
      CP children and compared with 61 normal controls. SOD, GPx and GR activities were
      spectrophotometrically assayed. Activities of SOD, GPx and GR in plasma did not
      differ significantly between CP children and the control group. Activities of
      erythrocyte GR in the CP patients were significantly lower compared with
      controls. MDA concentration did not differ statistically between the CP children
      and healthy subjects. In conclusion our results suggest that increased activities
      of erythrocyte GPx and decreased erythrocyte GR activities might be due to lesser
      physical activity of children with CP.

PMID- 15978630
TI  - Lipid rafts: a nexus for endocannabinoid signaling?
AB  - The endocannabinoids are endogenous agonists of the cannabinoid receptors and
      some members of the transient receptor potential, vanilloid type (TRPV), family
      of cation channels. Endocannabinoids along with their target receptors comprise a
      signaling system that is not well characterized. There have been many advances in
      our collective understanding of endocannabinoid signaling in the last decade and
      experimental evidence is mounting that pharmacological augmentation of
      endocannabinoid tone might have a significant therapeutic benefit in several
      disease states. However, the mechanisms responsible for the biosynthesis,
      cellular uptake, and intracellular processing of endocannabinoids are not well
      understood and have been the source of much debate. Recent studies have revealed
      a role for detergent insoluble membrane domains called lipid rafts in various
      aspects of signaling associated with the endocannabinoid anandamide. Intact
      detergent insoluble membrane domains appear to play a role in an anandamide
      induced signaling cascade that is independent of G protein-coupled cannabinoid
      receptors or TRPV channels. Furthermore, detergent insoluble membrane domain
      related endocytosis and recycling to lipid rafts appear to regulate the
      organization and localization of anandamide metabolites. We will discuss the
      implications that these findings have on the way we view endocannabinoid
      signaling, trafficking, and processing.

PMID- 15978629
TI  - Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or
      an acute colonic inflammation in the rat.
AB  - Nor-trimebutine is the main metabolite of trimebutine that is used in the
      treatment of patients with irritable bowel syndrome. Nor-trimebutine has a
      blocking activity on sodium channels and a potent local anesthetic effect. These
      properties were used to investigate the effect of nor-trimebutine on spinal
      neuronal activation induced by models of noxious somato-visceral stimulus and
      acute colonic inflammation. Nor-trimebutine was administered in rats either
      subcutaneously 30 min before intraperitoneal administration of acetic acid or
      intracolonically 30 min before intracolonic infusion of trinitrobenzenesulfonic
      acid. Abdominal contractions were counted for 1 h as a marker of abdominal pain.
      c-fos expression was used as a marker of neuronal activation and revealed by
      immunohistochemistry 1h after intraperitoneal acetic acid injection and 2 h after
      colonic inflammation. Nor-trimebutine decreased Fos expression in the thoraco
      lumbar (peritoneal irritation) and lumbo-sacral (colonic inflammation) spinal
      cord in laminae I, IIo V, VII and X. This effect was also observed in the sacral
      parasympathetic nucleus after colonic inflammation. Nor-trimebutine induced a
      significant decrease of abdominal contractions following intraperitoneal acetic
      acid injection. These data may explain the effectiveness of trimebutine in the
      therapy of abdominal pain in the irritable bowel syndrome.

PMID- 15978631
TI  - Cannabinoid receptor homo- and heterodimerization.
AB  - CB1 cannabinoid receptors mediate the psychoactive effects of Delta(9)THC and
      actions of the endogenous cannabinoids [Howlett, A.C., Barth, F., Bonner, T.I.,
      Cabral, G., Casellas, P., Devane, W.A., Felder, C.C., Herkenham, M., Mackie, K.,
      Martin, B.R., Mechoulam, R., Pertwee, R.G., 2002. International Union of
      Pharmacology: XXVII. Classification of cannabinoid receptors. Pharmacological
      Reviews 54 (2) 161-202.]. CB1 receptors belong to the G protein-coupled receptor
      (GPCR) superfamily. In recent years, it has become apparent that many GPCRs exist
      as multimers--either of like or unlike receptors [Kroeger, K.M., Pfleger, K.D.,
      Eidne, K.A., 2003. G-protein coupled receptor oligomerization in neuroendocrine
      pathways. Frontiers of Neuroendocrinology 24 (4) 254-278; Milligan, G., 2004. G
      protein-coupled receptor dimerization: function and ligand pharmacology.
      Molecular Pharmacology 66 (1) 1-7.]. Importantly, GPCR multimerization plays a
      key role in enriching the signaling repertoire of these receptors. In this
      review, the evidence for CB1 multimerization will be presented, the implications
      for cannabinoid signaling discussed, and possible future directions for this
      research considered.

PMID- 15978632
TI  - Arsenic trioxide induces Hsp70 expression via reactive oxygen species and JNK
      pathway in MDA231 cells.
AB  - In the present study, we determined the molecular pathways that induce the heat
      shock proteins (Hsps) after treatment of cells with arsenic trioxide.
      Administration of arsenic trioxide to MDA231 cells leads to induce Hsp70, which
      is accompanied by generation of reactive oxygen species (ROS) and activation of c
      Jun N-terminal kinase (JNK). We showed that arsenic trioxide-induced Hsp70
      expression was caused by activation of ROS and prevented by the antioxidant N
      Acetyl-Cysteine (NAC). SP600125 and dominant-negative SEK suppressed Hsp70
      promoter-driven reporter gene expression, suggesting that JNK would be
      preferentially associated with the protective heat shock response against arsenic
      trioxide stress. In addition, SP600125, a specific JNK inhibitor, significantly
      reduced the amount of phosphorylated HSF1 upon administration of arsenic
      trioxide. It is likely that Hsp70 expression against arsenic trioxide exposure
      protects cells from oxidative injury and apoptotic cell death by means of JNK
      activity.

PMID- 15978633
TI  - Castration induced changes in dog prostate gland associated with diminished
      activin and activin receptor expression.
AB  - This study was conducted to evaluate the effect of androgen ablation on dog
      prostate gland structure and the proliferation capacity of the prostatic cells
      and their association with the expression of Activin A and Activin RIIA receptor.
      The effect of androgen on the prostate gland was compared in intact and castrated
      dogs after one and two weeks. Specific primary antibodies were used to
      immunolocalize activin-A, activin receptor type II A and the proliferation marker
      (PCNA). The results showed that the glandular acini of the prostate gland of
      intact dogs are lined by tall columnar secretory cells and less abundant
      flattened basal cells and surrounded by a thin fibromuscular tissue. The
      cytoplasm of the glandular cells exhibited an intense immunoreaction for activin
      A and activin RIIA receptor while basal cells expressed PCNA. Castration induced
      a remarkable atrophy of the prostatic acini associated with a progressive loss of
      secretory epithelial cells, which showed a dramatic decrease to complete
      disappearance of Activin A and Activin RIIA receptor immunoreactions. The
      remaining cells of the atrophied acini continue to express PCNA and the inter
      acinar fibromuscular tissue showed a remarkable increase in its mass and are
      induced to express PCNA. These results indicated that androgen is required for
      the survival of epithelial cells and to maintain growth-quiescent fibromuscular
      cells, while basal cell proliferation is androgen independent. The changes in the
      Activin A and Activin RIIA receptor localization and their association with the
      dynamic pattern of prostate gland regression after castration suggested that
      Activin A and Activin RIIA receptor expression are androgen dependent.

PMID- 15978634
TI  - Inhibitory effect of 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide on
      nitric oxide and interleukin-6 production in macrophages.
AB  - 6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (CP compound) is a novel
      chemically synthetic compound with vitamin E-like chemical structure. In the
      present study, the CP compound was discovered to inhibit nitric oxide (NO) and
      interleukin (IL)-6 productions in lipopolysaccharide (LPS)-stimulated
      macrophages. Further, CP compound attenuated LPS-induced synthesis of mRNA and
      protein levels of inducible NO synthase (iNOS), in parallel, and inhibited iNOS
      promoter activity. In the similar way, CP compound inhibited LPS-induced
      synthesis of IL-6 transcript but also IL-6 promoter activity. These results
      indicate that CP compound could down-regulate LPS-induced iNOS and IL-6
      expression at the transcription step. As a mechanism of the anti-inflammatory
      action shown by CP compound, suppression of LPS-induced activation of both
      nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) has been
      documented. Finally, CP compound could provide an invaluable tool to investigate
      LPS-induced NF-kappaB and AP-1 activation, in addition to its therapeutic
      potential in NO- and IL-6-associated inflammatory diseases.

PMID- 15978635
TI  - In vitro prevention of cyclosporin-induced cell contraction by mycophenolic acid.
AB  - Nephrotoxicity is a major side-effect of cyclosporin A (CsA), which induces a
      vasoconstrictive response in vascular smooth muscle and mesangial cells.
      Mycophenolic acid (MPA) is used in combination with low-dose CsA to reduce
      nephrotoxicity. We previously demonstrated that MPA affected mesangial cell
      contractile response to angiotensin II or KCl. Aims of the present study were to
      evaluate if MPA can prevent CsA-induced contraction of human mesangial and aortic
      smooth muscle cells (ASMC). Using a morphoquantitative approach, we evidenced
      that pretreatment with MPA (1 microM) prevented the reduction of cell area
      induced by CsA within 30 min in both cell types. We then compared the expression
      of three main cytoskeleton proteins: tubulin, alpha-smooth actin (SMA) and basic
      calponin, in ASMC and in mesangial cells treated with MPA and/or CsA. CsA alone
      did not significantly change the expression level of these proteins neither in
      mesangial cells nor in ASMC. MPA decreased the expression level of tubulin in
      both mesangial cells and ASMC. Surprisingly, MPA, which stimulated SMA and
      calponin expression in mesangial cells, exerted an inhibitory effect on both
      contractile protein expression in ASMC. In conclusion, our results evidenced
      opposite effects of MPA on calponin and SMA protein expression in ASMC and in
      mesangial cells, despite similar antiproliferative properties, suggesting that
      sarcomeric protein expression is controlled by different intracellular mechanisms
      in mesangial and smooth muscle cells. However, MPA interferes in both cell types
      with the constrictive properties CsA, which may partially explain the protective
      effects of MPA against CsA nephrotoxicity.

PMID- 15978636
TI  - Differential effects of TAK-802, a selective acetylcholinesterase inhibitor, and
      carbamate acetylcholinesterase inhibitors on contraction of the detrusor smooth
      muscle of the guinea pig.
AB  - The aim of this study was to compare the effects of TAK-802, a novel
      acetylcholinesterase (AChE) inhibitor, and carbamate AChE inhibitors on the
      detrusor smooth muscle contractility in vitro using isometric tension
      measurements. The effects of drugs on the nicotine-induced contractions and basal
      tone of the isolated detrusor muscle of the guinea pig were examined. All of the
      drugs, namely, TAK-802, distigmine, neostigmine and pyridostigmine, enhanced the
      nicotine-induced contractions of the muscle strips in a concentration-dependent
      manner. On the other hand, while neostigmine and pyridostigmine markedly
      increased the basal tone, and distigmine slightly but significantly increased the
      basal tone, TAK-802 had no influence on the basal tone of the muscle strips at
      all. However, following co-treatment with tetraisopropyl pyrophosphoramide, a
      selective butyrylcholinesterase (BuChE) inhibitor, TAK-802 also did increase the
      basal tone. The increase of the basal tone by all of the above treatments was
      completely abolished by atropine. These results reveal that while all the four
      AChE inhibitors enhanced endogenous acetylcholine-induced contractions, their
      effects on the basal tone were clearly different. The effect of carbamate AChE
      inhibitors of increasing the basal tone could be partly attributed to their dual
      inhibition of both AChE and BuChE, because both cholinesterases may play a
      critical role in maintaining the resting tension of the urinary bladder. TAK-802,
      however, did not increase the basal tone of the detrusor muscle strips, probably
      because of its selective inhibitory effect against AChE. The effect of carbamate
      AChE inhibitors on the basal tone of the detrusor muscle may explain the decrease
      of bladder compliance observed in our previous study on guinea pigs as well as
      the deterioration of the bladder-storage function reported with their clinical
      use.

PMID- 15978637
TI  - The saponin monomer of dwarf lilyturf tuber, DT-13, reduces L-type calcium
      currents during hypoxia in adult rat ventricular myocytes.
AB  - The saponin monomer 13 of dwarf lilyturf tuber (DT-13), one of the saponin
      monomers of dwarf lilyturf tuber, has been found to have potent cardioprotective
      effects. In order to investigate the effects of DT-13 on L-type calcium currents
      (I(Ca,L)), exploring the mechanisms of DT-13's cardioprotective effects in the
      condition of pathophysiology, we directly measured the I(Ca,L) during hypoxia in
      the adult rat cardiac myocytes exposed to DT-13 using standard whole-cell patch
      clamp recording technique. Our previous results showed that DT-13 exerted
      decreasing effects on the I(Ca,L) of the single adult rat cardiac myocytes. In
      the condition of hypoxia, the current density was inhibited by about 29% after
      exposure of the cells to DT-13 (0.1 micromol L(-1)) for 10 min, from 6.96+/-1.05
      pA/pF to 4.38+/-0.35 pA/pF (n=5, P<0.05). This I(Ca,L)-inhibiting action of DT-13
      was concentration-dependent and showed no frequency-dependence. DT-13 up-shifted
      the current-voltage (I-V) curve. Steady-state activation of I(Ca,L) was not
      affected markedly, and the half activation potential (V(0.5)) in the presence of
      DT-13 (0.1 micromol L(-1)) was also not significantly different. DT-13 at 0.1
      micromol L(-1) markedly accelerated the voltage-dependent steady-state
      inactivation of calcium current and shifted the steady-state inactivation curve
      of I(Ca,L) to the left. In combination with previous reports, these results
      suggest that there might be a close relationship between the cardioprotective
      effects of DT-13 and L-type calcium channels in the condition of hypoxia.

PMID- 15978639
TI  - On the death of environmentalism.

PMID- 15978638
TI  - Regular physical exercise, heart rate variability and turbulence in a 6-year
      randomized controlled trial in middle-aged men: the DNASCO study.
AB  - HRV and HRT are independent predictors of cardiovascular mortality. Aging reduces
      HRV, but results from the physical exercise trials are controversial. The primary
      aim was to study changes in heart rate variability (HRV) and heart rate
      turbulence (HRT) in a six-year controlled randomized trial at regular low to
      moderate intensity physical exercise. One hundred forty men aged 53--63 years
      were randomized in to an exercise or a control groups. The participants underwent
      a maximal bicycle ergometer exercise test with respiratory gas analyses annually
      for six years. At baseline and after intervention, 24-h ambulatory ECG
      registrations were performed to assess HRV (n=100). HRT was determined among
      subjects with single ventricular premature complexes (VPC) (n=73). In the
      exercise group, ventilatory aerobic threshold (VAT) increased by 16% indicating
      enhanced submaximal cardiorespiratory fitness. No significant differences were
      found in any of the HRV or HRT parameters between the groups. However, the
      observed increase in VAT correlated significantly with the improvement in HRV
      parameters. The change in turbulence slope (TS) correlated with the changes in
      most HRV variables and the change in turbulence onset (TO) correlated with the
      changes in three frequency domain parameters. Our results suggest that in
      addition to improvement in submaximal cardiorespiratory fitness, regular low to
      moderate intensity physical exercise seems to have beneficial effects also on
      cardiac autonomic nervous function, a clinically relevant predictor of
      cardiovascular morbidity and mortality.

PMID- 15978640
TI  - Changes in the satiating effect of cholecystokinin over repeated trials.
AB  - The study investigated the reasons for discrepant published results concerning a
      diminution of the satiating action of cholecystokinin (CCK) when it is
      administered over several trials. Throughout the experiment, rats were maintained
      on a schedule in which they were fasted for 5.5 h (except 5 ml of milk), and then
      given access to a 10% sucrose solution for 30 min. Following a baseline period,
      rats received 6 mug/kg CCK-8 every day (consecutive group) or every third day
      (intermittent group), or saline (saline group), 15 min prior to the sucrose. In
      the consecutive group, CCK-8 significantly reduced meal size on day 1 (85.1+/
      7.4% of baseline) compared to the saline group (106.9+/-7.5% of baseline),
      p<0.05. This reduction was eliminated by day 5 (consecutive group=94.9+/-4.7% of
      baseline, saline group=98.0+/-5.2% of baseline). In contrast, the intermittent
      group never became insensitive to the effect of CCK-8, reducing their intake
      comparably after the tenth (intermittent group=138.7+/-8.2% of baseline, saline
      group=176.0+/-9.1% of baseline, p<0.01), and first CCK-8 injection (intermittent
      group=77.0+/-6.1% of baseline, saline group=106.9+/-7.5% of baseline, p<0.01).
      Although it has been hypothesized that this phenomenon is due to behavioral
      tolerance, the results of this experiment suggest an alternate hypothesis; i.e.,
      that the diminution of the effect of CCK-8 over consecutive administrations is
      due to the extinction of a previously learned response to endogenous CCK.

PMID- 15978641
TI  - MALDI-TOF mass spectrometry of oligomeric food polyphenols.
AB  - The structural heterogeneity of polyphenols from cranberries, grape seed
      extracts, sorghum and pomegranate was characterized by MALDI-TOF MS.
      Polyphenolics were isolated by liquid chromatography and subjected to MALDI-TOF
      MS using trans-3-indoleacrylic acid as the matrix. Spectrometric analysis gave
      information on degree of polymerization, monomeric substitution, and the nature
      of intermolecular bonds. Cranberry polyflavan-3-ols had variation in interflavan
      bonds (A- and B-types) and contained polyflavan-3-ols linked to anthocyanins
      through a CH3-CH bridge. Polygalloyl-polyflavan-3-ols in grape seed extract had
      large variation in the degree of galloyl substitution. Sorghum polyflavans had
      structural heterogeneity in glycosylation and hydroxylation. Pomegranate
      hydrolyzable tannins that correspond to previously described structures were
      detected, such as punicalagin, but others that correspond to oligomeric
      ellgitannins in which two to five core glucose units are cross-linked by
      dehydrodigalloyl and or valoneoyl units were also observed. Results demonstrate
      that large heterogeneity occurs in degree of polymerization, intermolecular
      bonds, pattern of hydroxylation, and substitution with monosaccharides and gallic
      acid.

PMID- 15978642
TI  - ent-Verticillane-type diterpenoids from the Japanese liverwort Jackiella
      javanica.
AB  - Three ent-verticillane diterpenoids and two ent-sesquiterpenoids were isolated
      from the Japanese liverwort Jackiella javanica Schiffn. together with five known
      ent-verticillane and three ent-kaurane diterpenoids, and three sesquiterpenoids.
      Five ent-verticillane epoxides were synthetically prepared from ent-verticillols
      action to clarify the absolute configuration of natural ent-9,10
      epoxyverticillol. Their structures were established by extensive NMR
      spectroscopic and X-ray crystallographic analyses.

PMID- 15978643
TI  - Molecular requirements of lignin-carbohydrate complexes for expression of unique
      biological activities.
AB  - Lignins are major cell wall components formed by the dehydrogenative
      polymerization of three monolignols, p-coumaryl, coniferyl and sinapyl alcohols.
      We prepared lignin-carbohydrate complexes (Fr. VI and Fr. VII) from pine cones by
      acid and ethanol precipitation, and investigated which part of these molecules is
      essential for expression of biological activities. They showed potent antiviral
      activity upon direct interaction with the virus. The antiviral activity of Frs.
      VI and VII required the higher-order structure of polyphenols without
      polysaccharides. Pretreatment of mice with Fr. VI or VII induced higher
      antiparasite activity than those of natural and chemically modified antitumor
      polysaccharides. Fr. VI or VII at higher concentrations enhanced the radical
      intensity and cytotoxic activity of vitamin C, whereas tannins counteracted the
      effect of vitamin C. Fr. VI at lower concentrations enhanced the O2(-)-scavenging
      activity of vitamin C. Frs. VI and VII stimulated mouse macrophage-like cells Raw
      264.7 to produce nitric oxide (NO), citrulline (CIT) and asparagine (ASN), via
      the enhanced expression of iNOS and ASN synthetase, whereas phenylpropenoid
      monomers and polymers inhibited NO/CIT/ASN production. These data suggest that
      the polymerized structure of phenylpropenoids in lignin-carbohydrate complexes is
      required for the induction of antiviral activity, and that the higher-order
      structure of phenylpropenoid polymers and polysaccharides is required for
      immunopotentiation, including macrophage activation.

PMID- 15978644
TI  - Lamb wave characteristics of thickness-graded piezoelectric IDT.
AB  - An equivalent single layer model of Lamb wave generation by thickness-graded
      piezoelectric IDT on host structure is developed. Various additional
      complexities, such as the coupling between the Lamb wave modes, complicated
      nature of the electro-mechanical excitation are considered. The model of infinite
      IDT is extended to deal with the finite IDT with edge discontinuities. The
      effects of electromechanical coupling and thickness gradation on the wavelength
      shifts are investigated. The problem of electrically driven instability within
      the IDT is analyzed. Numerical results are reported by considering Al2O3/PZT IDT
      as integral part of the host structure, which show that there are significant
      changes and improvements in the Lamb wave characteristics due to the graded
      configuration. Most important among these is the reduced dispersiveness of the
      Lamb wave modes, which is useful in launching a SAW that propagates with narrower
      pulse width and less attenuation.

PMID- 15978646
TI  - Precipitation recovery of boron from wastewater by hydrothermal mineralization.
AB  - It is well known that boric acid exhibits various toxic effects on plant, animal
      and human beings even at very low concentrations. Thus, the development of boron
      removal technique from wastewater has been intensively investigated. In this
      study, a new hydrothermal treatment technique was developed to recover boron as
      recyclable precipitate Ca(2)B(2)O(5).H(2)O from aqueous solutions. As a result,
      it was found that the hydrothermal treatment using calcium hydroxide as a
      mineralizer converted boron in the aqueous media effectively into calcium borate,
      Ca(2)B(2)O(5).H(2)O. In the optimal hydrothermal condition, more than 99% of
      boron was collected from the synthetic wastewater of 500 ppm. Thus, the present
      hydrothermal treatment in the presence of calcium hydroxide is recommended as one
      of the effective techniques to recover boron from aqueous media.

PMID- 15978645
TI  - Influence of water and sediment quality on benthic biota in an acidified river.
AB  - Water and sediment quality and benthic biota were investigated in all seasons
      during three years in the River Akagawa that receives the effluent from a mine
      drainage treatment plant at its upstream site. The upper reaches kept the low pH,
      the comparatively high concentrations of metals and a large amount of iron
      deposited on the riverbed. The predominant macroinvertebrates were Protonemura
      sp., Capnidae, Nemoura sp. and Chironomidae in the upper and middle reaches. In
      the lowest reaches, the community structure of the macroinvertebrate changed into
      Chironomidae, Trichoptera (Hydropsychidae) and Ephemeroptera (Baetis sp.) as the
      pH was increased. From the results of multivariate analyses, it was found that
      the restoration of pH and attached algae and the increase in the concentrations
      of nutrients and organic matter promoted the inhabitation of Chironomidae and
      Hydropsychidae, whereas the dissolved metals in the river water inhibited the
      inhabitation of these families. Moreover, the sedimentation of metals would cause
      a severe damage to the inhabitation of Hydropsychidae compared with that of
      Chironomidae.

PMID- 15978647
TI  - Seasonal tertiary wastewater treatment in California: an analysis of public
      health benefits and costs.
AB  - A number of communities in the Central Valley of California have requested that
      seasonally based effluent limits be developed for their wastewater treatment
      facilities. These seasonal limits would be based on disinfected secondary
      treatment during the winter and disinfected tertiary treatment during the rest of
      the year. Such a request for seasonal limits raises a significant water quality
      policy question with regard to the costs and relative benefits of tertiary
      treatment during the winter season. A benefit-cost analysis for winter season
      tertiary wastewater treatment in California's Central Valley is presented here.
      The assumed societal benefit of winter tertiary treatment is enhanced water
      quality for recreational purposes, and thus reduced risk to public health. Based
      on the results of this analysis, between four and sixteen million recreation
      events would need to occur annually region-wide during the winter to justify the
      costs of winter tertiary treatment. A similar method and the information
      described herein could be used by the state water quality regulatory agency to
      develop a risk-based policy to consider seasonal limits.

PMID- 15978648
TI  - Advective velocity and energy dissipation rate in an oscillatory flow.
AB  - Characterizing the transport processes at the sediment-water interface along
      sloping boundaries in lakes and reservoirs is of fundamental interest in lake and
      reservoir water quality management. The turbulent bottom boundary layer (TBBL)
      along a slope, induced by the breaking of internal waves in a linearly stratified
      fluid, was investigated through laboratory measurements. Fast response micro
      scale conductivity and temperature probes in conjunction with laser-Doppler
      velocimetry were used to measure the time series of salinity, temperature, and
      velocity along a sloping boundary. Turbulent energy spectra were computed from
      the velocity data using a time-dependent advective velocity and Taylor's
      hypothesis. The energy spectra were used to estimate the energy dissipation rate
      at different positions in the TBBL. The advective velocity in this near-zero mean
      shear flow is based on an integral time scale (T(int)). The integral time scale
      is related to the average frequency of the spectral energy density of the flow
      velocity. The energy dissipation rate estimated from the variable advective
      velocity with an averaging time window equal to the integral time scale
      (T=T(int)) was 43% higher than the energy dissipation rate estimated from a
      constant advective velocity. The estimated dissipation rates with T=T(int) were
      comparable to values obtained by curve-fitting a theoretical Batchelor spectrum
      for the temperature gradient spectra. This study proposes the integral time scale
      to be used for the oscillatory flows as (a) a time-averaging window to estimate
      the advective velocity and associated energy dissipation level, and (b) a
      normalizing parameter in the energy spectrum.

PMID- 15978649
TI  - Sulfide-iron interactions in domestic wastewater from a gravity sewer.
AB  - Interactions between iron and sulfide in domestic wastewater from a gravity sewer
      were investigated with particular emphasis on redox cycling of iron and iron
      sulfide formation. The concentration ranges of iron and total sulfide in the
      experiments were 0.4-5.4mgFeL(-1) and 0-5.1mgSL(-1), respectively. During
      anaerobic conditions, iron reduction kinetics were investigated and reduction
      rates amounted on average to 1.32mgFeL(-1)d(-1). Despite the very low solubility
      of iron sulfide, the reduced iron reacted only partly with sulfide to produce
      iron sulfide, even when dissolved sulfide was in excess. When a ferric chloride
      solution was added to sulfide containing anaerobic wastewater, the ferric iron
      was quickly reduced to ferrous forms by oxidation of dissolved sulfide and the
      ferrous iron precipitated almost completely as iron sulfide. During aerobic
      conditions, iron sulfide was oxidized with a half-life period of 11.7h. The
      oxidation rate of iron sulfide was significantly lower than that reported for the
      oxidation of dissolved sulfide.

PMID- 15978650
TI  - Effect of SRT and temperature on biological conversions and the related scum
      forming potential.
AB  - Sludge flotation was reported to cause several operational problems in anaerobic
      systems including UASB reactors treating both strong domestic sewage and some
      industrial wastewater. This research is to investigate the effect of anaerobic
      digestion on scum-forming potential (SFP) of sludge and other physical-chemical
      properties. A simple test was developed to measure and compare the tendency of
      different sludge to form a scum layer. Results showed that anaerobic digestion
      affects chemical composition of sludge flocs and consequently, SFP, which was
      found to be inversely proportional to the degree of digestion (both SRT and
      temperature). It was suggested that higher protein concentration at elevated SRT
      and 25 degrees C increased the negative surface charge of sludge flocs and
      ,consequently, reduced the ability of sludge to attach to gas bubbles and float.
      Floc average size increased with increasing SRT and temperature, especially for
      sludge with 75d SRT at 25 degrees C. On the other hand, settling properties of
      sludge were negatively affected by increasing SRT to 75d at 25 degrees C.
      Filterability had a strong positive correlation with average floc size, but also
      polymeric constituents correlated positively with filterability at 25 degrees C.

PMID- 15978651
TI  - Development of particle-based biofilms for degradation of xenobiotic organic
      compounds.
AB  - The aim of the experiments performed in this work was to develop a biofilm
      airlift suspension (BAS) process for the degradation of a mixture of organic
      sulfonates contained in the infiltration water from a contaminated site. To
      achieve this goal, active biomass growing on the contaminating xenobiotic
      organics as the sole source of carbon was obtained by enriching a mixed microbial
      culture sampled from an activated sludge treatment plant. After kinetic
      characterisation, the enriched culture was inoculated in the BAS reactor, where
      it colonised carrier particles and formed stable and uniform biofilms. In spite
      of the slow growth and degradation kinetics (mu(max)=0.014 h(-1)), due to high
      biomass concentration (up to 12 g(VS)L(-1)) a high rate process was performed in
      the BAS reactor, achieving a degradation capacity of 8.7 kg(COD)m(-3)d(-1), with
      an overall degradation efficiency of 70% based on COD measurements.

PMID- 15978652
TI  - Effects of oxygen concentration on N-removal in an aerobic granular sludge
      reactor.
AB  - In order to optimise nitrogen removal in an aerobic granular sludge system, short
      and long-term effects of decreased oxygen concentrations on the reactor
      performance were studied. Operation at decreased oxygen concentration is required
      to obtain efficient N-removal and low aeration energy requirement. A short-term
      oxygen reduction (from 100% to 50%, 40%, 20% or 10% of the saturation
      concentration) did not influence the acetate uptake rate. A lower aerobic acetate
      uptake at lower oxygen concentrations was obviously compensated by anoxic acetate
      uptake. Nitrogen removal was favoured by decreased oxygen concentrations,
      reaching a value of 34% for the lowest oxygen concentration tested. Long-term
      effects were evaluated at two oxygen saturation levels (100% and 40%). Nitrogen
      removal increased from 8% to 45% when the oxygen saturation was reduced to 40%.
      However, the granules started to disintegrate and biomass washout occurred. It
      was impossible to obtain stable granular sludge at this decreased oxygen
      concentration under applied conditions. A solution to obtain stable aerobic
      granular sludge at low oxygen concentrations is needed in order to make aerobic
      granular sludge reactors feasible in practice.

PMID- 15978653
TI  - Effect of chlorination on the formation of odorous disinfection by-products.
AB  - In order to explain some of the possible origins of an odor episode, which took
      place in a drinking water supply in the region of Paris (France), the
      chlorination reaction of some simple amino acids (valine, leucine and
      phenylalanine) was investigated. In addition to the commonly admitted
      intermediates and products of this reaction (monochloramines, aldehydes and
      nitriles), the formation of far less documented products was observed: N
      chloroaldimines which proved to present particular properties. These products
      appeared to remain relatively stable in water, especially at low temperatures,
      and can be formed under disinfection conditions relevant to those of drinking
      water treatment (i.e. at high chlorination rates). N-chloroaldimines also present
      strong swimming pool odors with a floral background, with odor detection
      thresholds close to 1microgL(-1) and even less. These values were established
      with a laboratory-made protocol. These products appeared more odorous than the
      corresponding aldehydes, known for a long time as potent odor causing chemicals
      and which have previously been involved in some odor problems in the field of
      drinking water treatment. N-chloroaldimines are consequently products of interest
      for water treaters and are now suspected to be a source of off-flavor concerns
      among consumers. We have therefore developed an analytical method (gas
      chromatography coupled with mass spectrometry) to demonstrate the presence of
      some of these compounds in water at concentrations close to their odor detection
      thresholds. Considering the levels of amino acids that can be reached in water,
      this level of chloroaldimines concentration could be obtained under certain
      pollution conditions.

PMID- 15978654
TI  - Phosphorous retention capacity of filter media for estimating the longevity of
      constructed wetland.
AB  - The filter medium could be selected and the longevity of the filter medium by the
      phosphorus saturation could be predicted in the constructed wetland system,
      accordingly proposing the scheme to remove the phosphorus for a long period. The
      phosphorus adsorption capacities of various filter media were investigated in
      relation to the size and types of filter media to screen the optimal condition.
      The objective of this study was to evaluate the constructed wetland longevity by
      improving P adsorption capacity. The maximum P adsorption capacities of filter
      media A (4--10 mm), B (2--4 mm), and C (0.1--2 mm) were 7.7, 11.6, and 22.5
      mg/kg, respectively, showing that they increased as the filter media size
      decreased. Among the experimental media, the optimal filter media size was 0.1--2
      mm. When Ca, Mg, Al and Fe were added to the filter medium C, which is the
      optimal filter medium, the addition of Ca improved mostly the P adsorption
      capacity. In the alternative proposal to use these facts, the oyster shell was
      added to the filter medium and the P adsorption capacity was examined: adding 2%
      oyster shell increased the P adsorption capacity from 23 to 36 mg/kg. In the
      column where the oyster shell was mixed, when the oyster shell content was 5%,
      10%, 20%, 40%, 60%, 80%, and 100% in the filter medium C, the respective
      saturation times of the P adsorption were about 6, 9, 17, 30, 43, 56, and 70
      days. When the oyster shell content was 0%, 5%, 10%, 20%, 40%, 60%, 80%, and 100%
      after 1 month in the column, the P adsorption amount was about 180, 600, 1560,
      4280, 6157, 7089, 7519, and 7925 mg/kg, respectively. The increment of the P
      adsorption amount was small if the oyster shell content was 60% or more, because
      the filter medium with more than 60% oyster shell content did not approach the
      saturation time by the P adsorption yet. The P adsorption amount for 60%, 80%,
      and 100% could be predicted as about 9702, 12,879, and 16,056 mg/kg,
      respectively. The largest amount of extracted P in the filter media with oyster
      shell after 30 days of P solution application was bound to Ca, followed by water
      soluble-P, Al--P, and Fe--P. Therefore, it was concluded that the adsorption
      amount of the phosphorus could be increased by adding the oyster shell to the
      filter medium. Also, it was concluded that adding the oyster shell to the filter
      medium in the constructed wetland was the scheme to extend the longevity of the
      constructed wetland by the phosphorus saturation, and using the oyster shell
      would be useful in aspect of economical efficiency and easiness. Especially, it
      would be the alternative proposal to reduce the environmental pollution in aspect
      of recycling wastes.

PMID- 15978655
TI  - Degradation of monocrotophos in soils.
AB  - The degradation of a widely used organophosphorus insecticide, monocrotophos
      (dimethyl (E)-1-methyl-2-methylcarbamoyl vinyl phosphate) in two Indian
      agricultural soils at two concentration levels, 10 and 100 microg g(-1) soil
      under aerobic conditions at 60% water-holding capacity at 28+/-4 degrees C was
      studied in a laboratory. The degradation of monocrotophos at both concentrations
      in black vertisol and red alfinsol soils was rapid accounting for 96-98% of the
      applied quantity and followed the first-order kinetics with rate constants (k) of
      0.0753 and 0.0606 day(-1) and half-lives (t1/2) of 9.2 and 11.4 days,
      respectively. Degradation of monocrotophos in soils proceeded by hydrolysis with
      formation of N-methylacetoacetamide. Even three additions of monocrotophos at 10
      microg g(-1) soil did not result in its enhanced degradation. However, there was
      cumulative accumulation of N-methylacetoacetamide in soils pretreated with
      monocrotophos to the tune of 7-15 microg g(-1) soil. Both biotic and abiotic
      factors were involved in degradation of monocrotophos in soils.

PMID- 15978656
TI  - Jarosite characteristics and its utilisation potentials.
AB  - During metallic zinc extraction from zinc sulphide or sulphide ore, huge quantity
      of jarosite is being released universally as solid residues. The jarosite mainly
      contains iron, sulphur, zinc, calcium, lead, cadmium and aluminium. Jarosite
      released from such industrial process is complex and its quality and quantity
      make the task more complex for safe disposal. Apart from water contamination,
      jarosite already accumulated and its increasing annual production is a major
      source of pollution for surrounding environment including soil, vegetation and
      aquatic life and hence its disposal leads to major concern because of the
      stringent environmental protection regulations. An attempt was made to evaluate
      the characteristics of Indian jarosite with an objectives to understand its
      potentials for recycling and utilising as raw materials for developing value
      added products. Sand and Coal Combustion Residues (CCRs) was used as an admixture
      to attain good workability and detoxify the toxic substance in the jarosite.
      Result revealed that jarosite is silty clay loam in texture having 63.48% silt
      sized and 32.35% clay sized particles. The particle size of jarosite (D90=16.21+/
      0.20 microm) is finer than the CCRs (D90=19.72+/-0.18 microm). The jarosite is
      nonuniform in structure and shape as compared to the CCRs having spherical,
      hollow shaped and some of them are cenosphere in nature. The major mineral phase
      of jarosite is Potassium Iron Sulphate Hydroxide {KFe3(SO4)2(OH)6}and Iron
      Sulphate Hydrate {2 Fe2O3SO3 x 5 H2O}. In CCRs the dominant phases are quartz
      {SiO2}, mullite {3 Al2O3 x 2 SiO2} and hematite {Fe2O3}. The high electrical
      conductivity of jarosite (13.26+/-0.437 dS/m) indicates that the presence of
      cations and anions are predominant over CCRs (0.498+/-0.007 dS/m). The major
      portion of jarosite consists of iron (23.66+/-0.18%), sulphur (12.23+/-0.2%) and
      zinc (8.243+/-0.075%). But CCRs main constituents are silicon (27.41+/-0.74%),
      aluminium (15.167+/-0.376%) and iron (4.447+/-0.69%). The other constituents such
      as calcium, aluminium, silicon, lead, and manganese are also present in the range
      of 0.5 to 5%. Heavy metals such as copper, chromium, and cadmium are found higher
      in jarosite as compared to the CCRs. The statistically designed experimental
      trials revealed that the density, water absorption capacity and compressive
      strength of fired jarosite bricks are 1.51 gm/cm3, 17.46% and 43.4 kg/cm2
      respectively with jarosite sand mixture in the ratio of 3:1 indicating the
      potentials in developing building materials.

PMID- 15978657
TI  - Water and solute mass balance of five small, relatively undisturbed watersheds in
      the U.S.
AB  - Geochemical mass balances were computed for water years 1992-1997 (October 1991
      through September 1997) for the five watersheds of the U.S. Geological Survey
      Water, Energy, and Biogeochemical Budgets (WEBB) Program to determine the primary
      regional controls on yields of the major dissolved inorganic solutes. The sites,
      which vary markedly with respect to climate, geology, physiography, and ecology,
      are: Allequash Creek, Wisconsin (low-relief, humid continental forest); Andrews
      Creek, Colorado (cold alpine, taiga/tundra, and subalpine boreal forest); Rio
      Icacos, Puerto Rico (lower montane, wet tropical forest); Panola Mountain,
      Georgia (humid subtropical piedmont forest); and Sleepers River, Vermont (humid
      northern hardwood forest). Streamwater output fluxes were determined by
      constructing empirical multivariate concentration models including discharge and
      seasonal components. Input fluxes were computed from weekly wet-only or bulk
      precipitation sampling. Despite uncertainties in input fluxes arising from poorly
      defined elevation gradients, lack of dry-deposition and occult-deposition
      measurements, and uncertain sea-salt contributions, the following was concluded:
      (1) for solutes derived primarily from rock weathering (Ca, Mg, Na, K, and
      H(4)SiO(4)), net fluxes (outputs in streamflow minus inputs in deposition) varied
      by two orders of magnitude, which is attributed to a large gradient in rock
      weathering rates controlled by climate and geologic parent material; (2) the net
      flux of atmospherically derived solutes (NH(4), NO(3), SO(4), and Cl) was similar
      among sites, with SO(4) being the most variable and NH(4) and NO(3) generally
      retained (except for NO(3) at Andrews); and (3) relations among monthly solute
      fluxes and differences among solute concentration model parameters yielded
      additional insights into comparative biogeochemical processes at the sites.

PMID- 15978658
TI  - Prospective evaluation of platelet B2 bradykinin and thrombopoietin receptor
      levels from preeclamptic compared to non-preeclamptic pregnancy patients.
AB  - Our recent study determined a difference between preeclamptic and non
      preeclamptic patients in platelet potentiation by thrombopoietin (TPO) of
      reactivity to collagen. The main conclusion was that non-preeclamptic, but not
      preeclamptic, pregnancy patients' platelets showed significant TPO potentiation
      at first and third trimesters. Since TPO or B2 Bradykinin platelet receptor
      levels might influence TPO potentiation, we obtained platelet samples from 187
      first trimester pregnant patients prospectively followed through pregnancy.
      Patients were additionally sampled at third trimester, delivery, and 4 to 6 weeks
      postpartum. A total of 43 patients, including 11 diagnosed as preeclamptic at
      third trimester, were sampled at least three different times. We used Western
      blotting normalized with glyceraldehyde 3 phosphate dehydrogenase as a loading
      and staining control. There were no significant differences in relative receptor
      levels between groups or sampling times using repeated measures ANOVA with the
      mixed model allowing for missing samples. While the mechanism for differences in
      thrombopoietin potentiation of platelet activation by collagen remains unknown,
      it may be a first trimester indicator of developing preeclampsia.

PMID- 15978659
TI  - A phase II evaluation of flavopiridol as second-line chemotherapy of endometrial
      carcinoma: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: A phase II study was conducted to determine the efficacy of single
      agent flavopiridol therapy in patients with recurrent or persistent endometrial
      adenocarcinoma refractory to established treatments. METHODS: Eligible patients
      with measurable disease who failed primary therapy including one cytotoxic
      regimen were eligible for the trial. They were treated with single agent
      flavopiridol (50 mg/m(2)/day, IV bolus days 1, 2, 3). Treatment was repeated
      every 21 days with dose adjustments made for toxicity. Patients were treated
      until progression of disease or adverse side effects precluded further therapy.
      RESULTS: A total of 26 patients were enrolled in the study of whom, 23 patients
      were eligible. There were no objective responses. Five patients had stable
      disease (22%), 15 (65%) had increasing disease, and response could not be
      assessed in 3 (13%). The most frequent side effects included anemia, neutropenia,
      and diarrhea, all of which appeared manageable. CONCLUSION: Flavopiridol as a
      single agent in the above dosing schedule appears to have minimal activity as
      second-line chemotherapy of endometrial adenocarcinoma.

PMID- 15978660
TI  - Post-breeding inflammation and endometrial cytology in mares.
AB  - Endometritis has been reported to be the third most common medical condition of
      horses. Timely diagnosis and treatment of endometritis in mares increases the
      chance of pregnancy. Exfoliative endometrial cytology is often used as a clinical
      tool to evaluate endometrial inflammation through detection of neutrophils. There
      is a lack of information on the time frame for changes in endometrial cytologic
      parameters following breeding. The main objectives of this article are to use
      current information to describe systematic analysis of endometrial cytology using
      standardized methods for sample collection and interpretation, and discuss how
      these parameters change in relationship to post-breeding interval and mare
      susceptibility.

PMID- 15978661
TI  - Endometritis in the mare: a diagnostic study comparing cultures from swab and
      biopsy.
AB  - The objective of this study was to compare results from endometrial culture swabs
      with results from culturing of endometrial biopsies. The culture results were
      related to cytological findings (polymorphonuclear; PMN-cells) and histological
      observations (PMN-cells). Biopsy and swab samples were smeared on the surface of
      a blood agar petri dish, and examined for growth of bacteria. Cytology samples
      were obtained from endometrial biopsies, stained and examined under microscopy
      for the presence of PMN-cells. Endometrial biopsies were examined for the
      presence of PMN-infiltration of the endometrial luminal epithelium and the
      stratum compactum. Using the presence of PMNs in a tissue specimen as the "best
      standard" for diagnosing endometritis, the sensitivity of bacterial growth from
      an endometrial biopsy was 0.82. The sensitivity for cytology was 0.77, and the
      sensitivity of bacterial growth from an endometrial surface swab was 0.34. The
      specificity for biopsy cultures, swab cultures, and cytology to diagnose
      endometritis were 0.92, 1.0, and 1.0 respectively. The positive predictive value
      for biopsy cultures, swab cultures, and cytology were 0.97, 1.0, and 1.0
      respectively. The negative predictive value for biopsy cultures, swab cultures,
      and cytology were 0.67, 0.44, and 0.62 respectively. In conclusion,
      bacteriological culture and cytology from an endometrial biopsy provide the
      practitioner with the most accurate results regarding both sensitivity and
      positive predictive value.

PMID- 15978662
TI  - Spontaneously forming hydrogel from water-soluble random- and block-type
      phospholipid polymers.
AB  - The mixed aqueous solutions of two water-soluble phospholipid polymers, such as
      poly[2-methacryloyloxyethyl phosphorylcholine(MPC)-co-methacrylic acid(MA)]
      (rPMA) and poly[MPC-co-n-butyl methacrylate(BMA)] (PMB), spontaneously form a
      hydrogel at room temperature without any chemical treatment due to hydrogen
      bonding formation between the carboxyl groups. With the objective of enhancing
      the hydrogen bonding efficiency, we have focused on the density of the carboxyl
      groups by controlling the chemical structure and monomer unit sequence. Thus, a
      random and an ABA-block-type MPC copolymer having carboxylic acids, poly[MPC-co-4
      (2-methacryloyloxyethyl) trimellitic acid(MET)] (rPMT) and poly(MA)-poly(MPC)
      poly(MA) (bPMA), have been designed. The purpose of this study is to investigate
      the gelation mechanism and physical properties of a hydrogel composed of rPMA and
      PMB (ABgel), one of bPMA and PMB (bABgel), and one of rPMT and poly(MPC-co-benzyl
      methacrylate) (PMBz) (TZgel). The Raman spectroscopic analysis and the
      rheological study of the dissolution behaviors indicated that the TZgel formation
      occurred due to inter- and intra-molecular hydrogen bonding formation between the
      carboxyl groups in the rPMT. The gelation mechanism of the bABgel was
      investigated by the dynamic light scattering measurement, the scanning electron
      microscopy observation and the rheological study. The results showed that the
      bPMA chains aggregate in the aqueous medium and transform into a hydrogel network
      structure. The bPMA needed much more gelation time than the rPMA due to this
      transformation. There was no difference between the gelation periods of the ABgel
      and the TZgel. The compression strengths of the ABgel and the bABgel showed no
      significant difference, while that of TZgel was lower than ABgel. The reason for
      this is that the polymer chains and bulky side chains of rPMT inhibit rearranging
      into a planar conformation and forming hydrogen bondings. These results lead to
      the conclusion that the properties of these MPC polymer hydrogels can be
      controlled by not only the chemical structure of the polymer but also the monomer
      unit sequence containing carboxyl groups.

PMID- 15978663
TI  - Inhibition of implant-associated infections via nitric oxide release.
AB  - The in vivo antibacterial activity of nitric oxide (NO)-releasing xerogel
      coatings was evaluated against an aggressive subcutaneous Staphylococcus aureus
      infection in a rat model. The NO-releasing implants were created by coating a
      medical-grade silicone elastomer with a sol-gel-derived (xerogel) film capable of
      storing NO. Four of the bare or xerogel-coated silicone materials were
      subcutaneously implanted into male rats. Ten rats were administered 10 microl of
      a 10(8) cfuml(-1)S. aureus colony directly into the subcutaneous pocket with the
      implant prior to wound closure. Infection was quantitatively and qualitatively
      evaluated after 8d of implantation with microbiological and histological methods,
      respectively. A 82% reduction in the number of infected implants was achieved
      with the NO-releasing coating. Histology revealed that the capsule formation
      around infected bare silicone rubber controls was immunoactive and that a biofilm
      may have formed. Capsule formation in response to NO-releasing implants had
      greater vascularity in comparison with uninoculated or untreated controls. These
      results suggest that NO-releasing coatings may dramatically reduce the incidence
      of biomaterial-associated infection.

PMID- 15978664
TI  - Influence of selected wound dressings on PMN elastase in chronic wound fluid and
      their antioxidative potential in vitro.
AB  - Exudates from non-healing wounds contain elevated levels of proteolytic enzymes,
      like elastase from polymorphonuclear granulocytes (PMN elastase), reactive oxygen
      species (ROS) and reactive nitrogen species (RNS). The overproduction of
      proteolytic enzymes leads to reduced concentrations of growth factors and
      proteinase inhibitors, resulting in an imbalance between degradation and
      remodelling processes. Thus, the reduction of protein-degrading enzymes and
      scavenging of ROS and RNS seem to be suitable ways to support the healing process
      of chronic stagnating wounds. The aim of this study was to test selected wound
      dressings from different biomaterials (collagen, oxidized regenerated cellulose
      (ORC) and ORC/collagen mixture), regarding their antioxidative potential in vitro
      and their influence on the concentration and activity of PMN elastase in chronic
      wound fluid. Antioxidant capacity of the investigated wound dressing was
      determined by a pholasin-based chemiluminescent assay. PMN elastase concentration
      was determined by means of ELISA. Enzyme activities could be measured by a
      fluorescence assay. As the presented data demonstrates, all tested materials
      showed antioxidant capacity. In addition, the investigated materials were able to
      reduce the concentration and activity of PMN elastase. Beside other aspects, such
      as biocompatibility, biodegradability, fluid absorption and clinical effects
      (e.g. angiogenesis and microcirculation), the understanding of these properties
      may help to support the further refinement of wound dressings for improved wound
      healing.

PMID- 15978665
TI  - C-terminal part of AgRP stimulates insulin secretion through calcium release in
      pancreatic beta Rin5mf cells.
AB  - Agouti-related protein (AgRP) is an orexigenic peptide which is composed of three
      parts; the amino (N)-terminus, the middle part, and the carboxyl (C)-terminus.
      AgRP has been implicated in various cell signaling, but the precise role of each
      parts are currently unclear. In this study, we have attempted to determine which
      part of AgRP was critical for insulin secretion. We have found that the C
      terminus of AgRP specifically increases the intracellular calcium concentration
      in pancreatic beta Rin5mf cells in a PLC-dependent manner, whereas the middle
      part and C-terminus have little effects on calcium release. This calcium response
      can be observed in the freshly isolated primary beta cells also. Moreover,
      amperometric measurement reveals that the C-terminus of AgRP increases the rate
      of exocytosis in Rin5mf cells. We further show that this region of AgRP is
      responsible for insulin secretion in a PLC-dependent manner. Taken together,
      these results indicate that the C-terminus of AgRP can participate in the insulin
      secretion in pancreatic beta cells, through the modulation of calcium release.

PMID- 15978666
TI  - In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their
      derivatives.
AB  - At immunolocalization of experimental tumors, idiotypic monoclonal antibodies,
      such as TS1 against cytokeratin 8, can be used to carry and deposit in vivo
      terapeutics in the tumor. These carriers also remain in the circulation and may
      cause negative side-effects in other tissues. In this report, several derivatives
      of the antiidiotypic antibody alphaTS1 were produced and tested for their
      clearing capacity of the idiotypic carrier antibody TS1. Intact monoclonal
      alphaTS1, scFv of a alphaTS1 and alphaTS1 Fab'2 and fragments were produced by
      recombinant technology or by cleavage with Ficin. The scFv was tailored by use of
      the variable domain genes of the light and heavy chain from the hybridoma clone
      in combination with a (Gly4Ser)3-linker, followed by expression in E. coli. When
      tested for clearing capacity, the intact divalent antiidiotypic IgG was found to
      be the most efficient. The divalent and the monovalent Fab fragment also
      demonstrated significant clearing, but lower than the intact antiidiotypic IgG.
      The alphaTS1 scFv antibody when injected separately was not found to clear the
      idiotype, but could do so when preincubated with the idiotype. Rapid excretion
      and in vivo instability of this low molecular weight antibody fragment may be the
      major reasons. Similar results were obtained when the system was reversed and the
      131I-labeled antiidiotype IgG was cleared with the idiotype fragment. It is
      concluded that both intact antiidiotypic IgG, and Fab'2 fragments are able to
      clear the idiotypic antibodies. The experimental data support the conclusion that
      the Fc parts from both the idiotype and the antiidiotype may contribute to this
      elimination.

PMID- 15978667
TI  - Computing spike directivity with tetrodes.
AB  - The ability of neurons to generate electrical signals is strongly dependent on
      the evolution of ion-specific pumps and channels that allow the transfer of
      charges under the influence of electric fields and concentration gradients. This
      paper presents a novel method by which flow of these charge fluxes may be
      computed to provide directivity of charge movement. Simulations of charge flow as
      well as actual electrophysiological data recorded by tetrodes are used to
      demonstrate the method. The propagation of charge fluxes in space in data from
      simulation and actual recordings during action potential can be analyzed using
      signals recorded by tetrodes. Variation in spike directivity can be estimated by
      computing singular value decomposition of the estimated 3D trajectory data. The
      analysis of the spike model can be accomplished by performing simulations of
      presumed equivalent moving charges recorded by the tetrode tips. For in vivo
      spike recordings, the variation of spike directivity could be obtained using
      several spikes of selected neurons considering the charge movement model (CMM).
      The relationship between computer simulation results and tetrode data recordings
      is examined. The paper concludes by showing that the method for calculating
      directivity in actual spike recordings is robust. The method allows for improved
      filtering of data and more importantly may shed light on furthering the study of
      spatio-temporal encoding in neurons.

PMID- 15978668
TI  - The repair of brain lesion by implantation of hyaluronic acid hydrogels modified
      with laminin.
AB  - The hyaluronic acid (HA) hydrogels modified with laminin were used for
      implantation in rat brain in present study, in order to investigate its effects
      in reparation of injury in the CNS. Cross-linked HA hydrogels were synthesized
      and their characteristics were analyzed. Laminin, an extracellular matrix
      protein, which participates in neuronal development and survival, was immobilized
      on the backbone of the hydrogels. Hydrogels unmodified and modified with laminin
      were implanted into cortical defects mechanically created in rats and their
      ability to improve tissue reconstruction was then evaluated. After 6 and 12 weeks
      of implantation, sections of brains were processed with Nissl and Glees staining
      for revealing neural cell bodies and fibers, with DAB histochemistry for
      detecting the blood vessels, as well as with immunocytochemistry for recognizing
      GFAP. The sections were also taken to SEM and TEM for ultrastructral examination.
      The results showed that the HA hydrogels synthesized had mechanical properties
      and rheological behavior similar to the brain tissue. After being implanted into
      the lesion of the cortex, the porous hydrogels created a scaffold, which could
      support cell infiltration and angiogenesis, and simultaneously inhibit the
      formation of glial scar. In addition, HA hydrogels modified with laminin could
      promote neurite extension. It seems possible that the tissue engineering
      technique may pave the way to repair injury in the CNS as suggested by the
      results in present study.

PMID- 15978669
TI  - A self-mixing laser-diode interferometer for measuring basilar membrane
      vibrations without opening the cochlea.
AB  - A laser-diode forms the basis of a displacement sensitive homodyne interferometer
      suitable for measurements from poorly reflective surfaces. The compact and cost
      effective interferometer utilizes the self-mixing effect when laser light
      reflected from a moving target re-enters the laser cavity and causes phase
      dependent changes of the lasing intensity. A piezo positioner was used to
      displace the interferometer with known frequency and amplitude as a basis for
      real-time calibration of the interferometer's sensitivity. The signal-processing
      algorithm is described that allows measurements in presence of high amplitude
      noise leading to variation of the interferometer's operating point. Measurements
      of sound-induced basilar membrane displacements were made in the intact cochleae
      of rodents by focusing the laser beam of the interferometer through the
      transparent round window membrane. The interferometer provides a viable means for
      making subnanometre mechanical measurements from structures in the inner ears of
      small mammals, where opening of the cochlea is not practicable.

PMID- 15978670
TI  - Relation between myelin area and axon diameter in the aortic depressor nerve of
      spontaneously hypertensive rats.
AB  - The hypothesis that the aortic depressor nerve (ADN) from spontaneously
      hypertensive rats (SHR) does not show the expected correlation between myelin
      sheath area and the axonal diameter of myelinated fibers detected in normotensive
      rat myelinated fibers was tested by means of regression analysis. Proximal and
      distal segments of ADN from 13 normotensive Wistar-Kyoto rats (WKY) and nine SHR
      were prepared for light microscopy study. With an image analysis system, the area
      of the myelin sheath and the axonal diameter of all myelinated fibers in each
      nerve were automatically measured. Regression lines were calculated for all nerve
      segments from each group. Differences between the regression lines were tested
      for slope and intercept and differences between the correlation coefficients were
      also tested. Regression lines for WKY data showed no differences between the
      proximal and distal segments either for slope or intercept. Proximal and distal
      SHR regression lines were not coincident between segments or when compared to WKY
      data. These results agree with previous observations that there are morphological
      differences between WKY and SHR myelinated fibers of the ADN suggesting that the
      SHR depressor nerve fibers present characteristics of axonal atrophy and/or
      remyelination.

PMID- 15978671
TI  - Cloning and expression of rabbit interleukin-15.
AB  - In order to understand the inflammatory mechanisms related to rabbit interleukin
      15 (RIL-15), we cloned and expressed RIL-15 cDNA gene. A cDNA encoding RIL-15 was
      cloned from heart mRNA by reverse transcriptase polymerase chain reaction (RT
      PCR) amplification using hIL-15 primers. The RIL-15 cDNA contains an open reading
      frame (ORF) of 162 amino acids (aa) with a 48 aa leader sequence. The predicted
      molecular weight of the encoded protein (12.5 kDa) matched the size of
      recombinant IL-15 on Western blotting in an Escherichia coli (pET32a) expression
      system. Amino acid and nucleotide sequence analyses of RIL-15 revealed 82.7% and
      87% homology with human IL-15 (hIL-15), respectively. RIL-15 is similar to the
      hIL-15 (hIL-15) in that it contains seven cysteine residues. RT-PCR showed that
      IL-15 is expressed in many tissues in the rabbit, including heart, spleen, lung,
      liver, muscle and kidney. Expressed and purified recombinant RIL-15, in the
      absence of the 48 aa leader sequence, stimulated the proliferation of cells of
      the mouse T cell line, CTLL-2, and its activity is comparable to hIL-15. Western
      blotting demonstrated that recombinant RIL-15 can be recognized by anti-IL-15
      neutralization antibody. Western blotting also confirmed that IL-15 is present in
      many tissues including heart, spleen, lung, liver, muscle and kidney.

PMID- 15978672
TI  - Viral interference with MHC class I antigen presentation pathway: the battle
      continues.
AB  - CD8+ cytotoxic T lymphocytes (CTLs) play a critical role in the defense against
      viral infections. In general, CD8+ CTLs recognize antigenic peptides in the
      context of the major histocompatibility complex (MHC) class I molecule. The MHC
      class I molecules are expressed on almost all the nucleated cells in the body.
      The trimolecular complex consisting of the class I heavy chain, beta2
      microglobulin and the peptide are generated by the MHC class I antigen
      presentation pathway. This pathway is designed to sample the intracellular milieu
      and present the information to the CTLs trafficking the area. This rigorous
      sampling of intracellular environment enables the CTLs to quickly identify and
      eliminate the cells that synthesize non-self proteins as a result of a viral
      infection. Many viruses, including several viruses of veterinary importance, have
      evolved astounding strategies to interfere with the MHC class I antigen
      presentation pathway, as a means of evading the CTL response of the host. This
      review focuses on the diverse mechanisms of viral evasion of the MHC class I
      antigen presentation pathway with particular emphasis on viruses of veterinary
      importance.

PMID- 15978673
TI  - Splenic norepinephrine depletion following acute stress suppresses in vivo
      antibody response.
AB  - Exposure to an intense acute stressor immediately following immunization leads to
      a reduction in anti-KLH IgM, IgG, and IgG2a, but not IgG1. Stress also depletes
      splenic norepinephrine (NE) content. Immunization during pharmacological (alpha
      methyl-p-tyrosine) or stress-induced splenic NE depletion results in antibody
      suppression similar to that found in rats immunized prior to stressor exposure.
      Prevention of splenic NE depletion during stress by tyrosine, but not
      pharmacological elevation (mirtazapine) of NE, resulted in normal antibody
      responses. These data support the hypothesis that splenic NE depletion is
      necessary and sufficient for stress-induced suppression of antibody to a T-cell
      dependent antigen.

PMID- 15978674
TI  - Familial bilateral abductor vocal cord paralysis.
AB  - Familial bilateral abductor vocal cord paralysis is a rare entity with few prior
      descriptions in the literature. Modes of inheritance include X-linked, autosomal
      recessive, and autosomal dominant. A case of this condition in a father and son
      is presented. Signs and symptoms at presentation, diagnosis, therapeutic
      considerations, and modes of inheritance are discussed.

PMID- 15978675
TI  - Bacteremia following pediatric adenoidectomy.
AB  - OBJECTIVE: Adenoidectomy is frequently performed in children. The goals of this
      work were to determine the incidence of bacteremia during the adenoidectomy, to
      identify the microorganisms implicated, and to analyze the possible association
      of bacteremia with postoperative complications. METHODS: One hundred pediatric
      patients operated of adenoidectomy without preoperative antibiotic prophylaxis
      were prospectively included in this study. They had no immunosuppressive and/or
      cardiovascular risk factors, no antimicrobial therapy for at least 15 days prior
      to operation, and no fever 1 week before surgery. Venous blood samples were
      obtained 30 s and 20 min after the curettage of adenoidal tissue. RESULTS: The 33
      and 14% of the samples were positive at 30 s and 20 min. The organism more
      commonly isolated was the streptococcus viridans. Bacteremia was only related to
      postoperative acute otitis media (p=0.012). CONCLUSIONS: Bacteremia exists after
      pediatric adenoidectomy, although it seldom correlates with clinical signs or
      symptoms. Postoperative acute otitis media is the only complication related to
      postsurgical bacteremia.

PMID- 15978676
TI  - The use of the Montgomery T-tube in difficult paediatric airways.
AB  - OBJECTIVE: We report our experience of using Montgomery T-tubes in children.
      METHOD: A retrospective review of medical records was performed. Data collected
      included particular clinical circumstances, the details of usage of the tube, and
      the eventual outcome. RESULTS: Between January 1999 and October 2003, our unit
      performed 293 tracheostomies, 76 laryngotracheal reconstructions and 31 other
      major airway procedures in children. 10 children have had a Montgomery T-tube
      inserted. Nine were boys. In eight cases, the T-tube was used because of severe
      granulations and subsequent fibrotic narrowing in the subglottis after
      laryngotracheal reconstruction surgery. These children had undergone between one
      and four major procedures prior to T-tube placement. In the other two cases, the
      T-tube was used to stent severe glottic and supraglottic stenosis (due to
      previous laser surgery for papillomas in one case and congenital ectodermal
      dysplasia in the other). At the time of T-tube placement the children were aged 2
      18 years (median 8 years). The tube was initially fitted so as to protrude above
      the glottis in all cases. In one case, the T-tube was removed on the first post
      operative day. One tube was removed after a week due to severe crusting. One tube
      blocked after 2 weeks. One child had re-stenosis in the supraglottis
      necessitating the placement of a T-tube with a longer upper limb. Two children
      have subsequently died from non-airway causes. Two children still have their T
      tube in situ, one of whom is due to have it removed in the next few weeks. Six
      have been successfully decannulated and are well. CONCLUSIONS: The Montgomery T
      tube provides a useful adjunct to the management of a small number of children
      with the most difficult airway problems. Its use can be problematic, however, and
      requires awareness of its specific complications. We have confined usage to
      complex stenoses where a reconstruction would be inappropriate, or (in one
      instance) to stent an unsupported larynx after revision reconstruction (tracheal
      resection).

PMID- 15978677
TI  - Drug eruptions in children with ENT infections.
AB  - OBJECTIVE: A common problem for the clinician in an outpatient clinic is to
      distinguish a drug eruption from a viral exanthem in a child. The aim of this
      study was to describe the common drug eruptions seen in children with ENT
      infections, suggesting an approach to this problem. METHODS: We studied the cases
      of ENT patients aged 15-years-old and below, with the clinical diagnosis of
      cutaneous adverse reactions. Main variables in the assessment of drug etiology in
      skin eruptions were previous experience with the drug in the general population,
      alternative explanation for the eruption, timing between the ingestion of the
      drug and the appearance of the lesions, drug levels or evidence of overdose or
      long-acting drug, subsequent progression of the eruption and reactions to
      dechallenge and rechallenge. RESULTS: A total of 47 children were examined during
      a period of 11 months. The indications for drug prescribed were tonsillitis,
      pharyngitis, rhinitis, otitis and sinusitis. The most usually implicated drugs
      were amoxycillin-clavulanic acid, cephalosporin, clindamycin, erythromycin,
      clarithromycin and paracetamol. The main clinical patterns of the eruptions seen
      were urticaria, maculopapular rash, fixed drug eruption and erythema multiforme.
      CONCLUSIONS: Careful clinical examination, detailed history, knowledge of the
      numerous clinical patterns of the eruptions and the drugs specific reaction
      rates, as well as oral drug rechallenge, RAST and patch tests if indicated, are
      essential factors in the management of patients with drug eruptions.

PMID- 15978678
TI  - Grisel's syndrome: a case report and review of the literature.
AB  - Grisel's syndrome is non-traumatic atlantoaxial subluxation (AAS) secondary to an
      inflammatory process in the upper neck. It is a rare condition that occurs almost
      exclusively in children and has been associated with upper cervical infections
      and otolaryngologic procedures. A case of AAS secondary to an upper cervical
      infection is presented. Potential sequelae can be severe; early diagnosis and
      treatment of Grisel's syndrome can prevent tragic outcome.

PMID- 15978679
TI  - Correlation of transiently evoked to distortion-product otoacoustic emission
      measures in healthy children.
AB  - OBJECTIVE: Transiently evoked (TEOAEs) and distortion-product otoacoustic
      emissions at the 2f1-f2 frequency (DPOAEs) are being used as a clinical tool for
      diagnosis of peripheral auditory pathology. Because both tests are fast and non
      invasive, they may be an excellent method for hearing screening in infants and
      children. The purpose of this study was to compare the TEOAE and DPOAE measures
      obtained in a group of healthy children. METHODS: Sixty-six school-aged children
      with normal hearing were included in the study. Subjects with recent otologic
      disease or abnormal tympanograms were excluded. TEOAEs and DPOAEs were performed
      using a DP Echoport ILO 292 Otodynamics analyzer connected to a portable personal
      computer. Correlation between TEOAE amplitudes and DPOAE levels was estimated.
      RESULTS: Correlation between TEOAE amplitudes and DPOAE levels was highly
      significant across all measured frequencies. Correlation was more significant at
      the middle frequencies than at the low and high frequencies. CONCLUSIONS:
      Although frequency specific information may be obtained by both tests, most
      reliable results were obtained at the middle frequencies. TEOAE values were more
      prominent at low frequencies, whereas DPOAEs were more effective at high
      frequencies. Both methods are reliable, objective, fast and useful tests of the
      cochlear status and should be included in the standard audiological diagnostic
      work-up of children.

PMID- 15978680
TI  - A novel way to spread drug resistance in tumor cells: functional intercellular
      transfer of P-glycoprotein (ABCB1).
AB  - Intercellular transfer of proteins is a mode of communication between cells that
      is crucial for certain physiological processes. Chemotherapy is the treatment of
      choice for approximately 50% of all cancers. However, multidrug resistance
      mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the
      effectiveness of such therapy in a large number of patients. A new study
      demonstrates the functional intercellular transfer of Pgp. Non-genetic transfer
      of the multidrug resistance phenotype raises fascinating questions about the
      mechanism and regulation of cell-surface membrane-protein-mediated spread of
      traits.

PMID- 15978681
TI  - Differential drug binding by the highly conserved Plasmodium falciparum
      thymidylate synthase.

PMID- 15978682
TI  - A type II ribonuclease H from Leishmania mitochondria: an enzyme essential for
      the growth of the parasite.
AB  - Replication of kDNA in the mitochondrion of the kinetoplastid protozoan is an
      essential process. One of the proteins that may be required for the kDNA
      replication is the ribonuclease H (RNase H; EC 3.1.26.4). We have identified four
      distinct ribonuclease H genes in Leishmania, one type I (LRNase HI) and three
      type II (LRNase HIIA, LRNase HIIB and LRNase HIIC). We detail here molecular
      characterization of LRNase HIIC. The coding sequence of LRNase HIIC is 1425 bp in
      length encoding a 474-amino acid protein with a calculated molecular mass of
      approximately 53 kDa. While LRNase HIIC shares several conserved domains with
      mitochondrial RNase H from other organisms, it has three extra patches of amino
      acid sequences unique to this enzyme. Functional identity of this protein as an
      RNase H was verified by genetic complementation in RNase H-deficient Escherichia
      coli. The precursor protein may be enzymatically inactive as it failed to
      complement the E. coli mutant. The mitochondrial localization signal in LRNase
      HIIC is within the first 40 amino acid residues at the N-terminus. In vitro
      import of the protein by the mitochondrial vesicles showed that the precursor
      protein is processed to a 49-kDa protein. Antisense ablation of LRNase HIIC gene
      expression is lethal to the parasite cells both in vitro and in vivo. This study
      not only reveals the significance of the LRNase HIIC in the kinetoplast biology
      but also identifies a potential molecular target for antileishmanial
      chemotherapy.

PMID- 15978683
TI  - Identification of a CaRAV1 possessing an AP2/ERF and B3 DNA-binding domain from
      pepper leaves infected with Xanthomonas axonopodis pv. glycines 8ra by
      differential display.
AB  - We isolated a cDNA clone, CaRAV1, which exhibited significant similarity to those
      of Arabidopsis RAV proteins containing AP2/ERF and B3-like DNA-binding domains.
      CaRAV1 expression was rapidly and specifically induced in both host and non-host
      resistant responses against bacterial pathogens in the chili pepper plant. CaRAV1
      also strongly increased following salicylic acid and ethephon treatments, whereas
      methyl-jasmonate only had mild effects. Furthermore, CaRAV1 transcript levels
      were also investigated in response to ABA and abiotic stress. No significant
      CaRAV1 expression was evident following ABA, mannitol, or cold treatments. These
      observations collectively provide initial evidence that the pepper RAV
      transcription factor homolog may function in plant defense responses.

PMID- 15978684
TI  - Correlation of regional cardiovascular disease mortality in India with lifestyle
      and nutritional factors.
AB  - OBJECTIVE: There is a wide disparity in prevalence and cardiovascular disease
      mortality in different Indian states. To determine significance of various
      nutritional factors and other lifestyle variables in explaining this difference
      in cardiovascular disease mortality we performed an analysis. METHODS AND
      RESULTS: Mortality data were obtained from the Registrar General of India. In
      1998 the annual death rate for India was 840/100,000 population. Cardiovascular
      diseases contribute to 27% of these deaths and its crude mortality rate was
      227/100,000. Major differences in cardiovascular disease mortality rates in
      different Indian states were reported varying from 75-100 in sub-Himalayan states
      of Nagaland, Meghalaya, Himachal Pradesh and Sikkim to a high of 360-430 in
      Andhra Pradesh, Tamil Nadu, Punjab and Goa. Lifestyle data were obtained from
      national surveys conducted by the government of India. The second National Family
      Health Survey (26 states, 92,447 households, 301,984 adults) conducted in 1998
      1999 reported on various demographic and lifestyle variables and India Nutrition
      Profile Study reported dietary intake of 177,841 adults (18 states, 75,229 men,
      102,612 women). Cardiovascular disease mortality rates were correlated with
      smoking, literacy levels, prevalence of stunted growth at 3-years (as marker of
      fetal undernutrition), adult mean body mass index, prevalence of overweight and
      obesity, dietary consumption of calories, cereals and pulses, green leafy
      vegetables, roots, tubers and other vegetables, milk and milk products, fats and
      oils, and sugar and jaggery. As a major confounder in different states is
      poverty, all the partial correlation coefficients were adjusted for illiteracy,
      fertility rate and infant mortality rate. There was a significant positive
      correlation of cardiovascular disease mortality with prevalence of obesity
      (R=0.37) and dietary consumption of fats (R=0.67), milk and its products (R=0.27)
      and sugars (R=0.51) and negative correlation with green leafy vegetable intake
      (R=-0.42) (p<0.05). CONCLUSIONS: There are large disparities in cardiovascular
      disease mortality in different Indian states. This can be epidemiologically
      explained by difference in dietary consumption of fats, milk, sugar and green
      leafy vegetables and prevalence of obesity.

PMID- 15978685
TI  - HDL: the 'new' target of cardiovascular medicine.
AB  - Clinical, experimental and epidemiological research has shown the undeniable
      causal relationship between low HDL plasma concentrations and cardiovascular
      disease. Low HDL levels are present in about 10% of the general population and
      represent the most frequent form of dyslipidemia in patients with coronary
      disease. Reduced HDL concentrations seem to be unable to eliminate efficiently
      the cholesterol excess at vascular wall level, contributing to the onset of the
      inflammatory response that typically occurs in the pathogenesis of
      atherosclerosis right from its earliest stages. The results of numerous studies
      quite convincingly suggest that HDL is capable of exerting anti-inflammatory
      activity either directly or by modulating the expression of a number of acute
      phase proteins. Although the therapeutic options currently available for raising
      HDL levels still show modest efficacy, both in experimental and pre-clinical
      fields, genetic investigation and specifically aimed pharmacological treatment
      have produced more encouraging results, shedding some light on the concrete
      possibility of being able to treat this disease in the very near future.

PMID- 15978686
TI  - All teas are not created equal: the Chinese green tea and cardiovascular health.
AB  - Tea is one of the most widely consumed beverages in the world, next only to
      water. It can be categorized into three types, depending on the level of
      fermentation, i.e., green (unfermented), oolong (partially fermented) and black
      (fermented) tea. In general, green tea has been found to be superior to black tea
      in terms of antioxidant activity owing to the higher content of (-)
      epigallocatechin gallate. The processes used in the manufacture of black tea are
      known to decrease levels of the monometric catechins to a much greater extent
      than the less severe conditions applied to other teas. The cardioprotective
      effect of flavonoids from green tea can be attributed to not only antioxidant,
      antithrombogenic and anti-inflammatory properties but also improvement of
      coronary flow velocity reserve. In this article, I will discuss the effects of
      green tea on atherosclerosis, coronary heart disease, hypertension, diabetes,
      metabolic syndrome and obesity, and, finally, its comparison with black tea.

PMID- 15978687
TI  - Reforming health care: evidence from quantile regressions for counts.
AB  - I consider the problem of estimating the effect of a health care reform on the
      frequency of individual doctor visits when the reform effect is potentially
      different in different parts of the outcome distribution. Quantile regression is
      a powerful method for studying such heterogeneous treatment effects. Only
      recently has this method been extended to situations where the dependent variable
      is a (non-negative integer) count. An analysis of a 1997 health care reform in
      Germany shows that lower quantiles, such as the first quartile, fell by
      substantially larger amounts than what would have been predicted based on Poisson
      or negative binomial models.

PMID- 15978688
TI  - Independent processing of visual stimulus changes in ventral and dorsal stream
      features indexed by an early positive difference in event-related brain
      potentials.
AB  - In event-related brain potential (ERP) studies of brain activity using a visual
      S1-S2 matching task, change stimuli elicit a posterior positive component with a
      latency of 100-200 ms. To elucidate the hierarchical organization of the
      processing of a visual stimulus change based on multiple stimulus features, ERPs
      were recorded in 12 participants performing an S1-S2 matching task with stimuli
      defined by color (mediated by the ventral stream) and motion direction (mediated
      by the dorsal stream). Each trial consisted of two sequentially presented stimuli
      (S1-S2), where S2 was either (1) the same as S1 (i.e., no change), (2) different
      from S1 in color only (color change), (3) different in motion direction only
      (motion direction change), or (4) different in both color and motion direction
      (color-motion direction change). These trials were presented in random order with
      equal probability, and the participants were asked to respond to one of these
      trials in separate blocks. Relative to the no-change stimulus, the three types of
      change stimuli elicited posterior positivities. The scalp-topography of change
      positivities differed according to the feature changed. In addition, the
      amplitude and scalp-topography of change positivities in response to a
      conjunction change were the respective sums of those in response to changes in
      the corresponding single features. These results suggest that the change
      detection system reflected by the change positivity is separate for each feature
      dimension, and these operate independently.

PMID- 15978689
TI  - Comparison of genotyping methods by application to Salmonella livingstone strains
      associated with an outbreak of human salmonellosis.
AB  - During 2000 and 2001, an outbreak of human salmonellosis occurred in Sweden and
      Norway, caused by Salmonella livingstone. In this study, the genotypic
      differences between three strains obtained from food sources during the outbreak,
      two human strains and 27 more or less unrelated strains were analysed, using the
      three methods; automated ribotyping, pulsed field gel electrophoresis (PFGE) and
      randomly amplified polymorphic DNA (RAPD). Each method was evaluated regarding
      its discriminatory ability, reproducibility and typeability. Simpson's
      discriminatory index calculated for each method was 0.556 for automated
      ribotyping, 0.766 for PFGE and 0.236 for RAPD. The reproducibility, defined as
      the minimum similarity between individual replicates in a cluster analysis, was
      96% for automated ribotyping and PFGE, and 90% for RAPD. All the strains were
      typeable with each method. When combining results for the three genotyping
      methods, it was found that RAPD did not increase the discriminatory index and was
      therefore excluded from further analysis. Using a combination of the results
      obtained from ribotyping and PFGE (D=0.855), two strains that had been isolated
      from feed factories during 1998 were shown to be identical to the outbreak
      strain, indicating a possible route of contamination due to a clone of Salmonella
      livingstone persisting in feed producing facilities. No connection to poultry was
      established.

PMID- 15978690
TI  - Microbial biomass production from rice straw hydrolysate in airlift bioreactors.
AB  - Rice straw is a by-product of rice production, and a great bioresource as raw
      biomass material for manufacturing value-adding protein for animal feedstock,
      which has been paid more and more attention. In the present work, utilizing rice
      straw hydrolysate as a substrate for microbial biomass production in 11.5L
      external-loop airlift bioreactors was investigated. Rice straw hydrolysate
      obtained through acid-hydrolyzing rice straw was used for the culture of yeast
      Candida arborea AS1.257. The influences of gas flow rate, initial liquid volume,
      hole diameter of gas sparger and numbers of sieve plates on microbial biomass
      production were examined. The best results in the external-loop airlift
      bioreactor were obtained under 9.0 L initial liquid volume, 1.1 (v/v)/min gas
      flow rate during culture time of 0-24 h and 1.4 (v/v)/min gas flow rate of 24-48
      h at 29+/-1 degrees C. The addition of the sieve plates in the riser of the
      external-loop airlift bioreactor increased productivity. After 48 h, under
      optimized operation conditions, crude protein productivity with one sieve and two
      sieves were 13.6 mg/mL and 13.7 mg/mL, respectively, comparing 12.7 mg/mL without
      sieves in the airlift bioreactor and 11.7 mg/mL in the in the 10-L mechanically
      stirred tank bioreactor. It is feasible to operate the external-loop airlift
      bioreactors and possible to reduce the production cost for microbial biomass
      production from the rice straw hydrolysate.

PMID- 15978691
TI  - DNA vaccine for rabies: relevance of the trans-membrane domain of the
      glycoprotein in generating an antibody response.
AB  - Various studies have demonstrated the potential of immunization with DNA vaccines
      encoding the rabies virus glycoprotein (RV-G) to elicit humoral responses. In the
      present study, we have designed four constructs using a VR1020 vector, wherein
      the RV-G ectodomain has been cloned without the signal sequence (SS) and the
      trans-membrane domain (TD) (rGVR), without the SS but with the TD (rGVRt), with
      the SS but without the TD (rGVRs) and with the SS and the TD (rGVRst), under the
      control of a cytomegalovirus (CMV) promoter, and downstream of the tissue
      plasminogen activator (TPA) signal sequence. In addition, RV-G has been expressed
      as a His6 tag fusion protein, both in Escherichia coli as well as in baculovirus
      expression systems. Using a prime-boost strategy, BALB/cJ mice administered with
      the rGVRt construct either in saline (intramuscularly) or adsorbed onto gold
      microcarriers (delivered intradermally by gene gun) generated the highest rabies
      virus neutralizing antibody (RVNA) titers. Inclusion of the SS, in addition to
      the TD (rGVRst), led to a significant decrease in RVNA titers, compared to the
      rGVRt construct. The DNA vaccine construct lacking both the SS and the TD domain
      and the vaccine having only the SS generated lower antibody responses, compared
      to the rGVRt construct. After priming with DNA vaccine, boosting with both E.
      coli- as well as baculovirus-expressed rRV-G led to an increase in the RVNA
      titers. The present results demonstrate that a DNA vaccine encoding the full
      length sequence of the ectodomain plus TD of the mature native RV-G is capable of
      expressing an 'ideal' immunogen to produce RVNA titers.

PMID- 15978692
TI  - Controlled release of anti-inflammatory agent alpha-MSH from neural implants.
AB  - Si-multi-electrode arrays implanted into brain tissue for long-term recording
      lose electrical connectivity due to the post-implantation inflammatory reaction.
      This inflammatory reaction creates a physical and electrical gap between the
      electrode and the surrounding neurons. In this study, novel nitrocellulose-based
      coatings were developed for the sustained delivery of the anti-inflammatory
      neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). alpha-MSH was
      incorporated in micron-scale nitrocellulose coatings and slow, sustained release
      over 21 days was attained in vitro. The alpha-MSH released on day 21 was still
      bioactive, and successfully inhibited nitric oxide (NO) production by LPS
      stimulated microglia. The amount of initial drug loading directly affected the
      release rate, with higher initial loading increasing the mass released but not
      the percent of drug released. The surface morphology and thickness of the
      coatings were examined by scanning electron microscopy (SEM) and profilometry. In
      addition, impedance measurement showed that the alpha-MSH loaded nitrocellulose
      coatings reduced the magnitude of electrode impedance at the biologically
      relevant frequency of 1 kHz. In conclusion, nitrocellulose-based, bioactive
      coatings that release anti-inflammatory agents without increasing the impedence
      of the electrode were successfully fabricated. These coatings have the potential
      to reduce inflammation at the electrode-brain interface in vivo, and facilitate
      long-term recordings from Si-multi-electrode arrays.

PMID- 15978693
TI  - A novel bacterium Achromobacter xylosoxidans as a cause of liver abscess: three
      case reports.
AB  - Achromobacter xylosoxidans is a microorganism that may cause opportunistic
      infections. We detected A. xylosoxidans in three of 46 patients with liver
      abscess. The clinicopathologic findings of the three patients were uniform with
      respect to a prior history of cholecystectomy, multi-lobulated 'coral-like'
      abscess under CT and epithelioid granulomas in the periphery of the abscess.
      Achromobacter xylosoxidans is an unrecognized cause of liver abscess in humans.

PMID- 15978694
TI  - Low-income Canadians' experiences with health-related services: implications for
      health care reform.
AB  - This study investigated the use of health-related services by low-income
      Canadians living in two large cities, Edmonton and Toronto. Interview data
      collected from low-income people, service providers and managers, advocacy group
      representatives, and senior-level public servants were analyzed using thematic
      content analysis. Findings indicate that, in addition to health care policies and
      programs, a broad range of policies, programs, and services relating to income
      security, recreation, and housing influence the ability of low-income Canadians
      to attain, maintain, and enhance their health. Furthermore, the manner in which
      health-related services are delivered plays a key role in low-income people's
      service-use decisions. We conclude the paper with a discussion of the health and
      social policy implications of the findings, which are particularly relevant
      within the context of recent health care reform discussions in Canada.

PMID- 15978695
TI  - The regional rule for bacterial base composition.
AB  - If one looks at the composition of coding DNA and of three types of intergenic
      regions--those between convergent, parallel and divergent genes--a striking
      pattern is seen in a wide range of bacteria. The AT-content of coding sequence is
      lowest, and the AT-contents of the intergenic regions increase in the order:
      convergent, parallel and divergent. Why does this pattern occur? In this article,
      I suggest an explanation based on the structural requirements for the binding of
      transcription factors.

PMID- 15978696
TI  - Wild-type alpha-synuclein interacts with pro-apoptotic proteins PKCdelta and BAD
      to protect dopaminergic neuronal cells against MPP+-induced apoptotic cell death.
AB  - Alpha-synuclein is a pre-synaptic protein of unknown function that has been
      implicated in the pathogenesis of Parkinson's disease (PD). Recently, we
      demonstrated that 1-methyl-4-phenylpyridinium (MPP+) induces caspase-3-dependent
      proteolytic activation of PKCdelta, which subsequently contributes to neuronal
      apoptotic cell death in mesencephalic dopaminergic neuronal cells. In the present
      study, we examined whether PKCdelta interacts with alpha-synuclein to modulate
      MPP+-induced dopaminergic degeneration. Over-expression of wild-type human alpha
      synuclein in mesencephalic dopaminergic neuronal cells (N27 cells) attenuated
      MPP+-induced (300 microM) cytotoxicity, release of mitochondrial cytochrome c,
      and subsequent caspase-3 activation, without affecting reactive oxygen species
      (ROS) generation. Wild-type alpha-synuclein over-expression also dramatically
      reduced MPP+-induced caspase-3-mediated proteolytic cleavage of PKCdelta, whereas
      over-expression of the mutant human alpha-synucleinA53T did not alter the
      PKCdelta cleavage under similar conditions. Immunoprecipitation-kinase assay
      revealed reduced PKCdelta kinase activity in wild-type alpha-synuclein over
      expressing cells in response to MPP+ treatment. Wild-type alpha-synuclein over
      expression also rescued mesencephalic dopaminergic neuronal cells from MPP+
      induced apoptotic cell death, while alpha-synucleinA53T exacerbated the MPP+
      induced DNA fragmentation. Furthermore, co-immunoprecipitation studies revealed
      that alpha-synuclein interacts with the pro-apoptotic proteins PKCdelta and BAD,
      but not with the anti-apoptotic protein Bcl-2 following MPP+ treatment. We also
      observed that the interaction between PKCdelta and alpha-synuclein does not
      involve direct phosphorylation. Together, our results demonstrate that wild-type
      alpha-synuclein interacts with the pro-apoptotic molecules BAD and PKCdelta to
      protect dopaminergic neuronal cells against neurotoxic insults.

PMID- 15978698
TI  - Clinical impact and relevance of antibiotic resistance.
AB  - Increasing antimicrobial resistance and multiple resistance have resulted in
      increasing difficulties in the treatment of bacterial infections. Resistance
      leads to inappropriate empirical therapy, delay in starting effective treatment,
      and the use of less effective, more toxic, and more expensive drugs. Although
      studies are not always consistent, antimicrobial resistance in the infecting
      organisms is associated with treatment failure, prolonged or additional
      hospitalization, increased costs of care, and increased mortality. Additional
      costs and lost bed days are incurred by the need to control the spread of
      antimicrobial-resistant organisms within hospitals. All this has significant
      direct impact on patients and their families and also secondary effects on the
      cost effectiveness of healthcare delivery. There is an urgent need to control
      antimicrobial resistance by improved antibiotic usage and reduction of hospital
      cross-infection.

PMID- 15978697
TI  - Variants of the primate vesicular monoamine transporter-2.
AB  - The vesicular monoamine transporter-2 (VMAT2) sequesters monoamine
      neurotransmitters into vesicles and prevents neurotoxicity. Human or monkey
      striatum generated three VMAT2 immunoreactive proteins of approximately 75 kDa,
      approximately 52-55 kDa, and approximately 45 kDa. The approximately 55-kDa band
      is considered the unglycosylated native protein. Deglycosylation of the VMAT2
      from striatum or human VMAT2 expressed in HEK293 cells yielded a approximately 45
      kDa, but not a 55-kDa immunoreactive band. We investigated this apparent mismatch
      between observed molecular size and predicted size.

PMID- 15978699
TI  - Effect of adrenomedullin administration on acetic acid-induced colitis in rats.
AB  - Adrenomedullin (AM) administered intracolonically ameliorated the severity of
      acetic acid-induced colonic ulceration in rats. Ulcers were induced by subserosal
      injection of acetic acid into the colon. AM-treated group was administered 0.25
      1.0 microg of AM in 0.5 ml of saline intracolonically once a day; the control
      group received only saline. AM administration dose-dependently and significantly
      reduced the size of the ulcerative lesions, the associated edema, and the
      infiltration of the affected area by inflammatory cells. AM also reduced tissue
      levels of interleukin-6, but not interferon-gamma. AM reduces the severity of
      acetic acid-induced colitis in rats, probably by inhibiting the production and/or
      release of Th-2 cell-derived factors such as interleukin-6.

PMID- 15978700
TI  - Corticotropin-releasing factor from the rat brain measured by protein immunoblot.
AB  - The ability to measure changes in brain levels of corticotropin-releasing factor
      (CRF) is an important step toward understanding the role of this neuropeptide in
      mood states. Here, we report for the first time that the protein (Western)
      immunoblot assay can be used to detect and quantify CRF (4.7 kDa) from the rat
      brain. Intracerebroventricular (ICV) injections of the neuronal transport
      inhibitor colchicine (0, 7.5, 15 and 75 microg) produced a dose-dependent
      increase in CRF levels within the paraventricular nucleus (PVN) of the
      hypothalamus with a concomitant and dose-dependent decrease in CRF levels within
      the median eminence (ME). These data provide a positive validation for the use of
      the immunoblot assay to detect treatment-induced changes in brain CRF levels.

PMID- 15978701
TI  - The phosphorylation of phospholipase C-gamma1, Raf-1, MEK, and ERK1/2 induced by
      a conserved retroviral peptide.
AB  - A synthetic 17-amino acid peptide (CKS-17) homologous to a highly conserved
      region of human and animal retroviral transmembrane proteins has been found to
      exhibit suppressive properties for numerous immune functions. It has been shown
      that CKS-17 causes an imbalance of human types 1 and 2 cytokines and inhibition
      of the immune responses of lymphocytes, monocytes, and macrophages. CKS-17
      induced increased intracellular levels of cAMP, which plays an important role in
      regulation of cytokine biosynthesis. In this study, using a Jurkat T-cell line
      and Western blot analysis, CKS-17 induced phosphorylation of PLC-gamma1, Raf-1,
      MEK and ERK1/2. Using a PLC selective inhibitor U73122 or PLC-gamma1-deficient
      Jurkat cell line, phosphorylation induced by CKS-17 of ERK1/2, PLC-gamma1, or Raf
      1, respectively, were undetectable or significantly reduced. Reintroduction of
      PLC-gamma1 into the PLC-gamma1-deficient Jurkat cells restored the
      phosphorylation of ERK1/2 and PLC-gamma1 induced by CKS-17. Further, pretreatment
      of Jurkat cells with PKC inhibitors blocks the phosphorylation of Raf-1, MEK, and
      ERK1/2 induced by CKS-17. These results indicate that CKS-17 induces the PLC
      gamma1-PKC-Raf-1-MEK-ERK1/2 signaling pathway.

PMID- 15978702
TI  - Proteolytic processing pattern of the endothelin-1 precursor in vivo.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor, which has been implicated in
      diseases involving dysfunctions of the cardiovascular system. For the biogenesis
      of ET-1, a larger precursor peptide (proET-1) is cleaved at two sites to give
      rise to bigET-1, which is subsequently cleaved to generate mature ET-1. In the
      present study, we investigated, which other peptides are derived from proET-1 in
      vivo. Six sandwich immunoassays covering various regions of proET-1 were
      developed and used to detect circulating proET-1 immunoreactivities in plasma of
      healthy subjects and septic patients. With this approach we could (a) demonstrate
      that, in addition to bigET-1/ET-1, three stable proET-1 fragments are generated,
      (b) exclude two previously discussed regions as sites for prohormone conversion
      and (c) show that the proteolytic processing pattern of proET-1 is unchanged
      under pathological conditions, which are associated with elevated levels of proET
      1 fragments. The high stability and similarity in concentration of the proET-1
      fragments suggest that these might be non-functional in the circulation. Stable
      proET-1 fragments maybe used in the future as reliable diagnostic targets to
      indirectly assess the release of ET-1, which might help to more selectively
      direct therapeutic measures.

PMID- 15978703
TI  - Recent developments in our understanding of the avian melanocortin system: its
      involvement in the regulation of pigmentation and energy homeostasis.
AB  - The mammalian melanocortin system has been established as a crucial regulatory
      component in an extraordinarily diverse number of physiological functions. In
      contrast, comparatively little is known about the avian melanocortin system:
      interest in the physiological role of alpha-MSH in birds has been limited by the
      fact that birds lack the intermediate lobe of the pituitary, the main source of
      circulating alpha-MSH in most vertebrates. Recently, however, the main avian
      melanocortin system genes, including POMC, AGRP, and all the melanocortin
      receptors, have been cloned and their physiological roles are the beginning to be
      elucidated. This review outlines our improved understanding of the avian
      melanocortin system, particularly in relation to two of the most widely studied
      physiological functions of the melanocortin system in mammals, the regulation of
      pigmentation and energy homeostasis. The data reviewed here indicate that the
      melanocortin system has been strongly conserved during vertebrate evolution and
      that alpha-MSH is produced locally in birds to act as an autocrine/paracrine
      hormone.

PMID- 15978704
TI  - Parenteral lipids modulate leukocyte phenotypes in whole blood, depending on
      their fatty acid composition.
AB  - To characterize the immunological effects of various lipids that are applied as
      part of total parenteral nutrition (TPN) formulations, we analyzed phenotypical
      changes in leukocytes following lipid exposure. Importantly, the study was
      performed with whole blood in order to prevent the functional changes that are
      induced by isolation procedures. Briefly, blood samples from 10 healthy
      volunteers were incubated with lipids containing pure long-chain triglycerides
      (L), mixed long- and medium-chain triglycerides (LM), synthetic structured lipids
      (SL), or emulsions based on olive oil (OO), or fish oil (FO). After immune
      fluorescent staining, leukocyte phenotype characteristics were analyzed by
      flowcytometry. Exposure to LM increased in a dose-dependent manner the expression
      of membrane surface markers for adhesion (CD11b) and degranulation (CD66b), while
      decreasing CD62L, on neutrophils and monocytes. These findings demonstrate that
      LM activates leukocytes in peripheral whole blood. On the other hand, decreased
      expression of activation markers was observed with L and FO. Lipids effects on
      the phenotype of T lymphocytes and Natural Killer cells were not seen during
      incubation for up to 4 h. These results indicate that (i) the composition of TPN
      formulations with regard to lipid structure has implications for the function of
      exposed immune competent cells and (ii) medium-chain triglycerides, which have
      been regarded as functionally inert deliverers of fuel calories, have distinct
      biological effects.

PMID- 15978705
TI  - Identification of DHBcAg as a potent carrier protein comparable to KLH for
      augmenting MUC1 antigenicity.
AB  - MUC1 is expressed at the cell surface of epithelial cancers. We have shown
      previously that MUC1 conjugated to keyhole limpet hemocyanin (KLH) plus the
      saponin immunological adjuvant QS-21 induces consistent high titer IgM and IgG
      antibodies in patients after treatment of their primary or metastatic cancers.
      KLH however is poorly soluble and heterogeneous making it difficult to work with,
      and we hypothesize that changing carrier proteins mid-way through a vaccination
      schedule would further increase antibody titers. Consequently, there is need for
      an alternative potent carrier protein. Duck Hepatitis B core antigen (DHBcAg) has
      a molecular weight of approximately 25kDa and is easily purified as a single
      band, but it self aggregates into particles of approximately 6.4x10(6)Da.
      Consequently, it is highly immunogenic, easy to work with and amenable to
      chemical and genetic conjugation to antigens such as MUC1. We compare here in
      mice the immunogenicity of MUC1 chemically conjugated to KLH or DHBcAg and MUC1
      DHBcAg recombinant protein after an initial series of three vaccinations and then
      after an additional series of three vaccinations with the same or opposite
      carrier, all mixed with the saponin immunological adjuvant GPI-0100. High titer
      IgG antibodies were observed in all groups after the initial three vaccinations:
      MUC1-DHBcAg median ELISA titer 1/51200, RecMUC1-DHBcAg 1/25600 and MUC1-KLH
      1/12800. This increased to 1/6553600 after the second set of three immunizations
      when the carrier remained the same in all three groups, but titers were
      significantly lower when the carriers were changed for the final three
      immunizations. These data demonstrate that DHBcAg is an excellent carrier protein
      and that changing carrier proteins does not further augment immunogenicity.

PMID- 15978706
TI  - Model testing for the remediation assessment of a radium contaminated site in
      Olen, Belgium.
AB  - Environmental assessment models are used as decision-aiding tools in the
      selection of remediation options for radioactively contaminated sites. In most
      cases, the effectiveness of the remedial actions in terms of dose savings cannot
      be demonstrated directly, but can be established with the help of environmental
      assessment models, through the assessment of future radiological impacts. It
      should be emphasized that, given the complexity of the processes involved and our
      current understanding of how they operate, these models are simplified
      descriptions of the behaviour of radionuclides in the environment and therefore
      imperfect. One way of testing and improving the reliability of the models is to
      compare their predictions with real data and/or the predictions of other models.
      Within the framework of the Remediation Assessment Working Group (RAWG) of the
      BIOMASS (BIOsphere Modelling and ASSessment) programme coordinated by IAEA, two
      scenarios were constructed and applied to test the reliability of environmental
      assessment models when remedial actions are involved. As a test site, an area of
      approximately 100 ha contaminated by the discharges of an old radium extraction
      plant in Olen (Belgium) has been considered. In the first scenario, a real
      situation was evaluated and model predictions were compared with measured data.
      In the second scenario the model predictions for specific hypothetical but
      realistic situations were compared. Most of the biosphere models were not
      developed to assess the performance of remedial actions and had to be modified
      for this purpose. It was demonstrated clearly that the modeller's experience and
      familiarity with the mathematical model, the site and with the scenario play a
      very important role in the outcome of the model calculations. More model testing
      studies, preferably for real situations, are needed in order to improve the
      models and modelling methods and to expand the areas in which the models are
      applicable.

PMID- 15978707
TI  - Sources of uncertainty in model predictions: lessons learned from the IAEA Forest
      and Fruit Working Group model intercomparisons.
AB  - The International Atomic Energy Agency (IAEA), through the BIOMASS program, has
      provided a unique international forum for assessing the relative contribution of
      different sources of uncertainty associated with environmental modeling. The
      methodology and guidance for dealing with parameter uncertainty have been fairly
      well developed and quantitative tools such as Monte-Carlo modeling are often
      recommended. The issue of model uncertainty is still rarely addressed in
      practical applications and the use of several alternative models to derive a
      range of model outputs (similar to what was done in IAEA model intercomparisons)
      is one of a few available techniques. This paper addresses the often overlooked
      issue of what we call 'modeler uncertainty,' i.e., differences in problem
      formulation, model implementation and parameter selection originating from
      subjective interpretation of the problem at hand. This study uses results from
      the Fruit and Forest Working Groups created under the BIOMASS program (BIOsphere
      Modeling and ASSessment). The greatest uncertainty was found to result from
      modelers' interpretation of scenarios and approximations made by modelers. In
      scenarios that were unclear for modelers, the initial differences in model
      predictions were as high as seven orders of magnitude. Only after several
      meetings and discussions about specific assumptions did the differences in
      predictions by various models merge. Our study shows that the parameter
      uncertainty (as evaluated by a probabilistic Monte-Carlo assessment) may have
      contributed over one order of magnitude to the overall modeling uncertainty. The
      final model predictions ranged between one and three orders of magnitude,
      depending on the specific scenario. This study illustrates the importance of
      problem formulation and implementation of an analytic-deliberative process in
      fate and transport modeling and risk characterization.

PMID- 15978708
TI  - Expression of bone morphogenetic protein-2 and proliferating cell nuclear antigen
      during distraction osteogenesis in the mandible in rabbits.
AB  - We examined the expression of bone morphogenetic protein-2 (BMP-2) and
      proliferating cell nuclear antigen (PCNA) during distraction osteogenesis in the
      mandible in rabbits. Twenty-four rabbits each had an osteotomy of the left
      mandibular body, and distraction devices were fixed. The bone was distracted at a
      rate of 1mm/day for 10 days. Four rabbits were killed at each of 1, 3, 7, 14, and
      28 days after completion of distraction, and the mandibles examined
      radiographically, histologically, and immunohistochemically. Four rabbits that
      had not been operated on served as controls. Immunohistochemical analysis showed
      that BMP-2 and PCNA both appeared initially at the edge of the osteogenesis, but
      tended to disappear after 14 days. After 1, 3, 7, and 14 days after distraction,
      the ratio of stained cells was significantly higher than in the control group
      (p<0.05), during the period that active bone formation was shown radiographically
      and histologically. These results suggest that BMP-2 plays an important part in
      the induction of bone formation during distraction osteogenesis.

PMID- 15978709
TI  - Generation of tumor-specific T-cell therapies.
AB  - Antigen-specific tumor immunotherapy remains an attractive strategy for the
      treatment of malignancies. In this review we will discuss why, despite the
      identification of large numbers of T cell recognised tumor antigens, effective
      immunotherapy remains a formidable challenge. Effective strategies are needed to
      deal with the tolerogenic properties of many tumor antigens, and with the
      immunocompromised status of patients. We discuss different methods of generating
      tumor-specific T cells which are currently being evaluated in clinical practice,
      such as vaccination and adoptive transfer of tumor antigen-specific T cells.
      Finally, we shall discuss novel strategies in development, such as the adoptive
      transfer of T cell receptor (TCR) gene modified T cells to establish antigen
      specific immunity in patients with leukemia and solid cancers. The transfer of
      validated high avidity TCRs, isolated from 'non-tolerant' repertoires or produced
      by in vitro affinity maturation, can serve to equip patient T cells with new anti
      tumor specificities that are not naturally present in the autologous repertoire.
      TCR transfer into CD4(+) and CD8(+) T cells can serve to harness the function of
      both helper and cytotoxic T cells for tumor elimination and establishment of long
      term tumor immunity.

PMID- 15978710
TI  - Influence of solid dairy manure and compost with and without alum on survival of
      indicator bacteria in soil and on potato.
AB  - We measured Escherichia coli, Enterococcus spp. and fecal coliform numbers in
      soil and on fresh potato skins after addition of solid dairy manure and dairy
      compost with and without alum (Al(2)(SO(4))(3)) treatment 1, 7, 14, 28, 179 and
      297 days after application. The addition of dairy compost or solid dairy manure
      at rates to meet crop phosphorus uptake did not consistently increase E. coli and
      Enterococcus spp. and fecal coliform bacteria in the soil. We did not detect E.
      coli in any soil sample after the first sampling day. Seven, 14, 28, 179 and 297
      days after solid dairy waste and compost and alum were applied to soil, alum did
      not consistently affect Enterococcus spp. and fecal coliform bacteria in the
      soil. We did not detect E. coli in any soil, fresh potato skin or potato wash
      water at 214 days after dairy manure or compost application regardless of alum
      treatment. Dairy compost or solid dairy manure application to soil at rates to
      meet crop phosphorus uptake did not consistently increase Enterococcus spp. and
      fecal coliform numbers in bulk soil. Solid dairy manure application to soil at
      rates to meet crop phosphorus uptake, increased Enterococcus spp. and fecal
      coliform numbers in potato rhizosphere soil. However, fresh potato skins had
      higher Enterococcus spp. and fecal coliform numbers when solid dairy manure was
      added to soil compared to compost, N and P inorganic fertilizer and N fertilizer
      treatments. We did not find any E. coli, Enterococcus or total coliform bacteria
      on the exterior of the tuber, within the peel or within a whole baked potato
      after microwave cooking for 5 min.

PMID- 15978711
TI  - Reevaluation of mortality risks from nasopharyngeal cancer in the formaldehyde
      cohort study of the National Cancer Institute.
AB  - OBJECTIVE: To determine whether the National Cancer Institute's (NCI) recent
      suggestion of a causal association between formaldehyde exposure and mortality
      from nasopharyngeal cancer (NPC) is robust with respect to alternative methods of
      data analysis and alternative categorizations of formaldehyde exposure. METHODS:
      The original authors provided the cohort data. We computed U.S. and local county
      (regional) rate-based standardized mortality ratios (SMRs) and internal cohort
      rate-based relative risks (RR) by categories of four formaldehyde exposure
      metrics (highest peak, average intensity, cumulative, and duration of exposure),
      using both NCI categories and an alternative categorization based on tertiles of
      all NPC deaths among exposed subjects. We computed SMRs and RRs for each of 10
      study plants and by plant group (Plant 1 (n = 4261) vs. Plants 2-10 (n =
      21,358)). RESULTS: Six of 10 NPC deaths observed in the NCI study occurred in
      only one plant (Plant 1) and the remaining four cases occurred individually in
      four of the other nine plants studied. A large, statistically significant,
      regional rate-based NPC SMR of 10.32 (95% CI = 3.79-22.47) among formaldehyde
      exposed workers in Plant 1 contrasted sharply with a 35% deficit in NPC deaths
      (SMR = .65, 95% CI = .08-2.33) among exposed workers in Plants 2-10 combined. The
      statistically significant exposure-response relationship with formaldehyde and
      NPC reported in the NCI study for highest peak exposure was driven entirely by a
      large, statistically significant excess NPC risk in Plant 1 for the highest peak
      exposure category (4+ ppm). For the remaining nine plants, RRs for all non
      baseline highest peak exposure categories were less than 1.0, and we observed no
      evidence of an exposure-response relationship. Most of the observed NPC excesses
      for the non-baseline categories of the other exposure metrics (average intensity,
      cumulative, and duration of formaldehyde exposure) were concentrated in Plant 1,
      and by contrast to the NCI findings, none of the corresponding exposure-response
      relationships was statistically significant. CONCLUSIONS: Overall, our reanalysis
      provided little evidence to support NCI's suggestion of a causal association
      between formaldehyde exposure and mortality from NPC. NCI's conclusion of a
      possible causal association was driven heavily by anomalous findings in one study
      plant (Plant 1). An independent and larger study of Plant 1 by the current
      authors concluded the NPC excess was not associated with formaldehyde exposure.
      Our findings cast considerable additional uncertainty regarding the validity of
      NCI's suggested causal association.

PMID- 15978712
TI  - Spousal influence on smoking behaviors in a US community sample of newly married
      couples.
AB  - Among married couples, partners often have similar characteristics and behaviors.
      Among individuals who smoke cigarettes, it is not uncommon for them to have a
      partner who also smokes. In fact, having a partner who smokes can influence the
      spouse's initiation of smoking, or return to smoking after a previous quit
      attempt. Additionally, it is possible that a nonsmoking partner can influence
      his/her spouse to stop smoking. Participants for this research are from a
      community sample of couples in the United States. They were recruited at the time
      they applied for their marriage license and followed through to their second
      wedding anniversary. Logistic regression models, controlling for demographics,
      were utilized to determine if a partner's smoking status predicted smoking
      initiation or relapse over the early years of marriage. Overall, there was some
      support that a partner's smoking status did influence the other's smoking,
      although more support was found for spousal influence on relapse than cessation.
      There was more support for husband's influence compared to wife's influence,
      nonsmoking wives were more likely to resume smoking in the early years of their
      marriage if their partners were smokers. Wives' smoking, however, did not predict
      husband initiation of smoking. These findings suggest that during the transition
      into marriage, spouses do influence their partners' behaviors. In particular,
      women are more likely to resume smoking, or return to smoking if their partners
      smoke.

PMID- 15978713
TI  - An alpha,beta-unsaturated oxime identified as a strong contact allergen.
      Indications of antigen formation via several pathways.
AB  - The aim of this study was to examine the possible skin sensitizing effect of
      oximes, employing an alpha,beta-unsaturated oxime as the model compound. Oximes
      are not frequently used as biologically active compounds. However, they have been
      shown to possess both anti-inflammatory and anti-allergic activities.
      Furthermore, in a recent study, a number of oximes and oxime-ethers of
      hydroxylated benzaldehydes and acetophenones were found to be powerful
      antioxidants suggested to be used in consumer products such as cosmetics and
      food. Although there are only few reports on the sensitizing effect of oximes,
      their ability to be hydrolyzed to the corresponding ketones or aldehydes makes
      them potential contact allergens. The oxime investigated in this study was
      demonstrated to be a strong contact allergen in both mice and guinea pigs,
      capable of sensitize the control animals after only one dermal exposure. In order
      to elucidate the mechanisms for the formation of the complete antigen, a variety
      of analogues with different reactivity were tested. The results indicate that
      alpha,beta-unsaturated oximes can react with proteins via several different
      pathways. Most likely, a metabolic transformation is involved. Due to the strong
      allergenic effect of the oxime investigated, we strongly advise against the use
      of such oximes in consumer products until a better understanding of their
      interactions with biological macromolecules has been obtained.

PMID- 15978714
TI  - Five-year clinical evaluation of two adhesive systems in non-carious cervical
      lesions.
AB  - OBJECTIVE: This controlled clinical trial evaluated the 5-year clinical
      performance of a self-etching primer system including selective enamel-etching
      with phosphoric acid and a one-bottle adhesive system. METHODS: Seventy-two non
      carious cervical lesions in 8 patients (4 male and 4 female) with a mean age of
      61.3 years (range 45-78) participated in the study. An enamel bevel was placed
      and dentin lightly ground, and cavities restored with clearfil liner bond II (LB)
      or single bond (SB) in conjunction with a hybrid resin composite (Clearfil AP-X).
      In the case of 27 cavities for LB, the enamel was pretreated with 37% phosphoric
      acid for 10 s. Each patient received both types of restoration, which were
      distributed on a random basis. All restorations (37 restorations for LB and 35
      restorations for SB) were placed by one dentist. The restorations were evaluated
      blind after 5 years using modified USPHS criteria. The data were statistically
      analyzed using the Fisher's exact test. RESULTS: All but one restoration (which
      was replaced by a crown after the 2-year recall) were evaluated after 5 years.
      100% retention rates were recorded for both restorative groups. No caries was
      detected in association with any restorations. The only minor problem was
      marginal discoloration; superficial and localized marginal discoloration occurred
      around 18% of the restorations, and mainly at the dentin margin. There were no
      significant differences in the marginal integrity between the LB and SB groups.
      CONCLUSIONS: Restorative materials used in this study demonstrated a good
      clinical effectiveness in the restoration of non-carious cervical lesions for 5
      years.

PMID- 15978715
TI  - Prediction of subjective states from psychophysiology: a multivariate approach.
AB  - Biocybernetic systems utilise real-time changes in psychophysiology in order to
      adapt aspects of computer control and functionality, e.g. adaptive automation.
      This approach to system design is based upon an assumption that
      psychophysiological variations represent implicit fluctuations in the subjective
      state of the operator, e.g. mood, motivation, cognitions. A study was performed
      to investigate the convergent validity between psychophysiological measurement
      and changes in the subjective status of the individual. Thirty-five participants
      performed a demanding version of the Multi-Attribute Task Battery (MATB) over
      four consecutive 20-min blocks. A range of psychophysiological data were
      collected (EEG, ECG, skin conductance level (SCL), EOG, respiratory rate) and
      correlated with changes in subjective state as measured by the Dundee Stress
      State Questionnaire (DSSQ). MATB performance was stable across time-on-task;
      psychophysiological activity exhibited expected changes due to sustained
      performance. The DSSQ was analysed in terms of three subjective meta-factors:
      Task Engagement, Distress and Worry. Multiple regression analyses revealed that
      psychophysiology predicted a substantial proportion of the variance for both Task
      Engagement and Distress but not for the Worry meta-factor. The consequences for
      the development of biocybernetic systems are discussed.

PMID- 15978716
TI  - Examination marks of male university students positively correlate with finger
      length ratios (2D:4D).
AB  - Intersexual and intrasexual variation in second to fourth digit length (2D:4D) in
      humans may result from differential exposure to fetal testosterone. 2D:4D
      predicts several physiological, psychological and performance traits in
      adulthood. These relationships may reflect the 'pleiotropic' effects of
      testosterone on development of digits and diverse organ systems, which are
      expressed in adulthood. We hypothesized that 2D:4D also predicts academic success
      of students. 2D:4D of right hand positively predicted examination marks of males
      from two three-year degree courses (TYDCs). Marks of females did not covary with
      2D:4D. Males from the two TYDCs differed in 2D:4D. The present results thus add
      to the rapidly accumulating literature on 2D:4D showing correlations with
      phenotypic traits in humans. If testosterone affects 2D:4D and intellectual
      performance, our results suggest that testosterone levels are under stabilizing
      selection because of effects on performance traits documented in previous studies
      and antagonistic effects on intellectual performance (present study).

PMID- 15978717
TI  - Effects of sleep reduction on spatial attention.
AB  - To investigate the effects exerted by sleep loss on specific attentive components
      the performance to a simple reaction time task and to a cued reaction time task
      were recorded at regular intervals during days following either 8 or 3 h of
      uninterrupted sleep. Eleven subjects took part in the experiment. The results
      show that, notwithstanding a general reduction of alertness produced by sleep
      curtailment (as indicated by the increase of reaction times in the simple
      reaction time task), in the cued reaction time task only the reaction times to
      invalidly cued targets significantly increase, while no difference is observed
      when attention is summoned by a valid cue. This result suggests that the
      mechanisms underlying orienting of attention are differentially affected by the
      reduction of alertness level.

PMID- 15978718
TI  - Bisphosphonates decrease telomerase activity and hTERT expression in MCF-7 breast
      cancer cells.
AB  - Bisphosphonates are important in the management of tumours with secondary bone
      involvement. Recent findings have suggested that these drugs also have an effect
      on primary tumour burden. Telomerase is a cellular ribonucleoprotein reverse
      transcriptase responsible for elongation of the telomere. Telomerase expression
      is increased in many cancers. We studied the direct effects of clodronate,
      alendronate, and pamidronate (from 10(-6) to 10(-4) M) on MCF-7 human breast
      cancer cell line. In particular, we investigated their effect on viability,
      proliferation, apoptosis, human telomerase reverse transcriptase expression (h
      TERT) by RT-PCR and telomerase activity. Alendronate and pamidronate showed an
      inhibition of viability (-63 and -35%, respectively; p < 0.0001) and
      proliferation of cancer cells, while no effect was observed with clodronate.
      Amino-bisphosphonates induced a significant increase of apoptosis in MCF-7. In
      addition, they showed a significant decrease in telomerase expression and
      activity with respect to control and to clodronate.

PMID- 15978719
TI  - Suppression of murine mammary carcinoma metastasis by the murine ortholog of
      breast cancer metastasis suppressor 1 (Brms1).
AB  - The murine ortholog (Brms1) of human breast cancer metastasis suppressor 1 shares
      95% identity to the human metastasis suppressor, BRMS1, in amino acid structure.
      We tested Brms1 for suppression of metastasis of mouse mammary carcinoma cell
      line 4T1 in syngenic BALB/c mice, using orthotopic (mammary fat pad) injection as
      well as intravenous injection. As observed for BRMS1, transfection with Brms1 did
      not inhibit 4T1 primary tumor formation, but significantly suppressed lung
      colonization. We also show that Brms1 protein interacts with histone
      deacetylases, indicating involvement of Brms1 in murine Sin3-HDAC complex, like
      its human counterpart. Thus, because of similarities with its human ortholog, the
      results suggest that Brms1 will be useful as a model for studying mechanism of
      action of BRMS1.

PMID- 15978720
TI  - Molecular mechanisms of aging-associated inflammation.
AB  - A direct relationship exists between aging and increasing incidences of chronic
      diseases. In fact, with most age-associated diseases individuals manifest an
      underlying chronic inflammatory state as evidenced by local infiltration of
      inflammatory cells, such as macrophages, and higher circulatory levels of pro
      inflammatory cytokines, complement components and adhesion molecules.
      Consequently, treatment with anti-inflammatory agents provide symptomatic relief
      to several aging-associated diseases, even as remote as Alzheimer's or
      Parkinson's disease, indicating that chronic inflammation may play a substantial
      role in the pathogenesis of these disease states. The molecular mechanisms
      underlying this chronic inflammatory condition during cellular senescence is
      presently unclear. Cellular damage by oxygen free radicals is a primary driving
      force for aging and increased activation of redox-regulated transcription
      factors, such as NF-kappaB that regulate the expression of pro-inflammatory
      molecules, has been documented in aged animals/individuals versus their young
      counterparts. Human polynucleotide phosphorylase (hPNPase(old-35)), a RNA
      degradation enzyme shown to be upregulated during differentiation and cellular
      senescence, may represent a molecular link between aging and its associated
      inflammation. hPNPase(old-35) promotes reactive oxygen species (ROS) production,
      activates the NF-kappaB pathway and initiates the production of pro-inflammatory
      cytokines, such as IL-6 and IL-8. In these contexts, inhibition of hPNPase(old
      35) may represent a novel molecular target for intervening in aging-associated
      chronic diseases.

PMID- 15978721
TI  - The reactions of sulfur mustard with the active components of organic
      decontaminants.
AB  - Reactions of sulfur mustard with active components of decontaminants ORO and C9
      (Polish abbreviations of organic decontaminating solutions) were studied and
      their products were identified by GC/AED. Quantitative determinations of
      individual products in the reaction mixtures allowed to evaluate the kinetic
      parameters of the mustard reactions. The major decontamination product was
      divinyl sulfide, the product of the elimination reaction. At certain proportions
      of mustard to the decontaminant's active component, substitution products were
      also formed.

PMID- 15978722
TI  - Thermo-chemical destruction of polychlorinated biphenyls (PCBs) in waste
      insulating oil.
AB  - The feasibility of thermo-chemical destruction of polychlorinated biphenyls
      (PCBs) was investigated using a batch reactor and two different (vertical and
      horizontal) types of continuous reactor. A simple batch reactor was first
      designed and constructed to examine applicability of thermal-chemical destruction
      of PCBs. It was evidenced from the batch test results that the destruction of
      PCBs in the insulating oil (40% PCBs, w/w) was accomplished via abiotic
      dechlorination and mineralization of PCBs with quicklime at 600 degrees C under
      nitrogen environment. PCB destruction efficiencies were obtained about 99.95%.
      The reaction was exothermic resulting release of heat by which the reactor
      temperature suddenly increased up to 750 degrees C at the incipient 30 min of the
      experiment. Two major end products, CaCl2 and carbon, were identified. For a
      practical purpose, two continuous reactors were developed and tested. The
      observed continuous test results indicate that over 99.99% of PCB destruction
      efficiencies were achieved when excess quicklime (>3Ca:1Cl2 as a molar basis) was
      used. Specifically, the horizontal continuous reactor was suitable in view of
      ease of solid transfer, which is essential for complete destruction of PCBs and
      for full-scale applications.

PMID- 15978723
TI  - Alternative pathways for catecholamine action in oral motor control.
AB  - Orofacial movement is a complex function performed by facial and jaw muscles. Jaw
      movement is enacted through the triggering of motoneurons located primarily in
      the trigeminal motor nucleus (Mo5). The Mo5 is located in the pontine reticular
      formation, which is encircled by premotor neurons. Previous studies using
      retrograde tracers have demonstrated that premotor neurons innervating the Mo5
      are distributed in brainstem areas, and electrophysiological studies have
      suggested the existence of a subcortical relay in the corticofugal-Mo5 pathway.
      Various neurotransmitters have been implicated in oral movement. Dopamine is of
      special interest since its imbalance may produce changes in basal ganglia
      activity, which generates abnormal movements, including jaw motor dysfunction, as
      in oral dyskinesia and possibly in bruxism. However, the anatomical pathways
      connecting the dopaminergic systems with Mo5 motoneurons have not been studied
      systematically. After injecting retrograde tracer fluorogold into the Mo5, we
      observed retrograde-labeled neurons in brainstem areas and in a few forebrain
      nuclei, such as the central nucleus of the amygdala, and the parasubthalamic
      nucleus. By using dual-labeled immunohistochemistry, we found tyrosine
      hydroxylase (a catecholamine-processing enzyme) immunoreactive fibers in close
      apposition to retrograde-labeled neurons in brainstem nuclei, in the central
      nucleus of the amygdala and the parasubthalamic nucleus, suggesting the
      occurrence of synaptic contacts. Therefore, we suggested that catecholamines may
      regulate oralfacial movements through the premotor brainstem nuclei, which are
      related to masticatory control, and forebrain areas related to autonomic and
      stress responses.

PMID- 15978724
TI  - Survey on porcine trichinellosis in Ecuador.
AB  - A survey on porcine trichinellosis was organised in Ecuador between 2000 and
      2003. Blood samples were taken in slaughterhouses (study 1, n=2000; study 2,
      n=331) and in a remote village where pigs are free roaming (study 3, n=646) and
      examined by ELISA using excretory/secretory (E/S) antigens. Seven samples (0.35%)
      in study 1 and none of the samples of study 2 were serologically positive. Thirty
      seven (5.72%) village pigs tested positive by E/S ELISA in study 3. Sero-positive
      results by the E/S ELISA in study 1 were confirmed by ELISA using beta-tyvelose
      antigen, and by immunoblot. Muscle samples taken from pigs slaughtered in the
      abattoir (study 2) and from animals that showed a positive serology in study 3
      were examined by trichinoscopy and artificial digestion. These techniques failed
      to demonstrate the presence of muscle larvae. The results of this survey need
      confirmation, but suggest that Trichinella is present in Ecuador; however,
      prevalence and parasite burdens are likely to be very low. The likelihood of
      detecting trichinellosis are higher in traditional settings than in pigs raised
      on improved farms.

PMID- 15978725
TI  - Trichuris suis excretory secretory products (ESP) elicit interleukin-6 (IL-6) and
      IL-10 secretion from intestinal epithelial cells (IPEC-1).
AB  - Immune responses to gastrointestinal helminth infections have received increasing
      attention due to similarities to allergen-induced responses. In fact, the
      whipworm parasite of swine, Trichuris suis, has been used in beginning clinical
      trials as an antidote to inflammatory bowel disease. This strategy was based on
      this similarity and the recognition that other worms have been documented to
      induce anti-inflammatory responses in the host. In an effort to understand the
      basis for this response, we hypothesized that the proteins and peptides secreted
      by T. suis stimulate local intestinal epithelial cells to produce anti
      inflammatory cytokines. To test this hypothesis in a correlate system of the
      natural swine host, T. suis excretory secretory products (ESP) were used to treat
      both differentiated and undifferentiated intestinal pig epithelial cells (IPEC-1)
      in vitro as a model for the effect on villus tip and crypt epithelial cells in
      the vicinity of the worms. IPEC-1 were exposed to low-level doses (0.3mg/ml) of
      T. suis ESP, and IL-4, IL-6 and IL-10 cytokine responses were measured by an
      enzyme-linked immunosorbant assay (ELISA). IL-6 was the predominant cytokine
      produced, accompanied by moderate IL-10 secretion from both differentiated and
      undifferentiated cells. As expected, IL-4 was not produced by IPEC-1.
      Additionally, IL-6 and IL-10 cytokines were produced within 24h, suggesting that
      these two cytokines form part of the primary host response to T. suis infections.
      These data suggest that T. suis ESP could enhance host immune responses and
      modulation through the induction of enteric IL-6 and IL-10.

PMID- 15978726
TI  - Species composition of Gasterophilus spp. (Diptera, Oestridae) causing equine
      gastric myiasis in southern Italy: parasite biodiversity and risks for
      extinction.
AB  - Horse gastrointestinal myiasis caused by larvae of Gasterophilus spp. (Diptera,
      Oestridae) flies has a worldwide distribution and, where present, it is primarily
      caused by larvae of Gasterophilus intestinalis and Gasterophilus nasalis. Other
      species, i.e., Gasterophilus inermis, Gasterophilus pecorum and Gasterophilus
      haemorrhoidalis, present in different or in the same regions of the
      gastrointestinal tract, were only occasionally reported in very limited areas of
      eastern European Countries and in central Italy. With the aim to contribute data
      on the species composition of Gasterophilus and on the seasonal variation of the
      infection pattern in southern Italy, 152 native horses were necropsied from
      January to December 2003 and Gasterophilus larvae were collected from the
      stomach, the small intestine and the rectum of each of them. On the whole, 125
      (82.2%) horses were infected by larvae of Gasterophilus spp. and 214 second stage
      larvae (L2) and 13,342 third stage larvae (L3) collected. Five species of
      Gasterophilus were identified with the following prevalence: G.
      intestinalis=95.2%, G. nasalis=44.8%, G. inermis=15.2%, G. pecorum=2.6% and G.
      haemorrhoidalis=0.8%. L3 were retrieved throughout the observation period with
      the highest mean burdens from January to August 2003 while the lowest mean was
      registered from September to November 2003. L2 were collected in February-March
      2003 and from September to December 2003. The majority of the animals (n=66,
      43.4%) were infected with a single Gasterophilus species, however, 45 animals
      (29.6%) harboured 2 species, 12 animals (7.9%) 3 species and 2 animals (1.3%) 4
      species. The trend of abundance in the L3 of G. intestinalis and G. nasalis, the
      most represented species, was highly concordant (r=0.5, p<0.001). A retrospective
      comparison of our results and of other data from four seasons of observation
      (1983-1986) in central Italy showed that the number of G. inermis, G. pecorum and
      G. haemorrhoidalis have been decreasing relative to G. intestinalis and G.
      nasalis which may suggest tendency toward the extinction of the three former
      species of Gasterophilus.

PMID- 15978727
TI  - Serological changes in goats experimentally infected with Fasciola gigantica in
      Buea sub-division of S.W.P. Cameroon.
AB  - Based on the recent increase in the rearing of West African Dwarf (WAD) goats in
      this environment, a study of biochemical parameters was carried out in healthy
      and infected goats to obtain baseline data for monitoring the health and
      productive indices in breeding programmes for the goats. The results revealed
      variations in some of the parameters studied. The serum minerals potassium,
      chlorine and bicarbonate did not show any significant differences (P>0.05)
      between the infected and control groups of goats, but there was a significant
      difference (P<0.0001) in sodium, calcium and urea levels. For serum lipids
      cholesterol and triglyceride, there were significant (P<0.0001) differences
      between the infected and control group. This goes same for serum proteins,
      albumin and total proteins. However, serum enzymes, serum glutamic oxaloacetic
      transaminase (SGOT) and gamma glutamyl transferase (GGT) were not significantly
      different (P>0.05) between the infected and control groups. There was a
      significant difference (P<0.0001) in alkaline phosphatase (ALP) and serum
      glutamic pyruvic transaminase (SGPT) between the infected and control groups.

PMID- 15978729
TI  - Serological evidence of Trichinellosis in local pigs of Nepal.
AB  - In Nepal, animal husbandry is a major source of income. Pig husbandry is
      practiced in rural, peri-urban, and urban communities. Free ranging "back yard"
      pigs and the practice of feeding offal is a very common management practice which
      potentially allows for the transmission of trichinellosis; however, this zoonosis
      has never been reported from this region. A total of 425 serum samples were
      collected from local pigs. These were initially screened by ELISA after which
      positive samples were examined by Western blot. This procedure identified two
      samples which had clear specific bands for Trichinella; however, muscle samples
      tested by HCL-pepsin digestion were found to be negative. If these highly
      specific serological analyses are confirmed, this would be the first report of
      trichinellosis in Nepal and a prevention program should be initiated to limit the
      access of pigs to open garbage dumps which exist both in towns and on farms.

PMID- 15978728
TI  - Confirmed clinical Neospora caninum infection in a boxer puppy from Argentina.
AB  - Generalized neosporosis was diagnosed in a 2-month-old boxer puppy. The dog had a
      history of progressive paralysis and muscle atrophy, followed by cervical
      weakness, stiff jaws and dysphagia. The dog had a 1:12,800 antibody titer for
      Neospora caninum and was negative for antibodies to Toxoplasma gondii by the
      indirect fluorescent antibody test (IFAT). After euthanasia a complete necropsy
      was carried out. The puppy had a megaesophagus. Microscopically, tachyzoites and
      tissue cysts were observed in histologic brain sections. Severe myositis was
      observed in esophagus and striated muscle sections and several groups of
      tachyzoites were associated with these lesions. Immunohistochemically, parasites
      in the brain and striated muscle reacted to anti-N. caninum antiserum. Western
      blot analysis allowed the identification of three major and four minor antigens
      of N. caninum tachyzoites corresponding to 30, 37, 45-kDa and 28, 29, 43, 47 and
      67-kDa bands, respectively. Cerebral homogenate of the dog was inoculated into
      four Mongolian gerbils (Meriones unguiculatus). Forty-nine days after
      inoculation, all the gerbils had positive IFAT titers to N. caninum (1:200,
      1:400, 1:100 and 1:400). Genomic DNA was isolated from the brain, lung and
      striated muscle from the puppy and from the brain of one of the inoculated
      gerbils. The N. caninum specific primer pair Np 6/21 produced 328 bp amplicons on
      electrophoretic gels. This is the first confirmed clinical case of generalized
      canine neosporosis in Argentina.

PMID- 15978730
TI  - Evaluation of the speciation status of aluminium(III) ions in isolated
      osteoarthritic knee-joint synovial fluid.
AB  - High field 1H NMR spectroscopy demonstrated that the equilibration of added
      Al(III) ions in osteoarthritic (OA) knee-joint synovial fluid (SF) resulted in
      its complexation by citrate and, to a much lesser extent, tyrosine and histidine.
      The ability of these ligands, together with inorganic phosphate, to compete for
      the available Al(III) in terms of (1) thermodynamic equilibrium constants for the
      formation of their complexes and (2) their SF concentrations was probed through
      the use of computer speciation calculations, which considered low-molecular-mass
      binary and ternary Al(III) species, the predominant Al(III) plasma transport
      protein transferrin, and also relevant hydrolysis and precipitation processes. It
      was found that, at relatively low added Al(III) concentrations, citrate species
      were more favoured, whilst phosphate species became dominant at higher levels.
      The significance of these findings with regard to the in vivo corrosion of
      aluminium-containing metal alloy joint prostheses (e.g., TiAlV alloys) is
      discussed.

PMID- 15978731
TI  - Characterization of benzodiazepine binding site on human alpha1-acid glycoprotein
      using flunitrazepam as a photolabeling agent.
AB  - The binding of flunitrazepam (FNZP) by human alpha1-acid glycoprotein (hAGP) and
      the relationships between the extent of drug binding and desialylation and the
      genetic variants of hAGP were examined. The photolabeling specificity of [3H]FNZP
      was confirmed by findings in which other hAGP-binding ligands inhibited the
      formation of covalent bonds between [3H]FNZP and hAGP. The photolabeling of
      asialo-hAGP suggested that sialic acid does not involve in the binding of
      [3H]FNZP. No difference in the labeling could be found between the F1*S variants
      and A variant. Similarly, FNZP did not show a difference in binding affinity to
      the two genetic variants of hAGP. Sequence analysis of the photolabeled peptide
      indicated a sequence corresponding to Tyr91-Arg105 of hAGP.

PMID- 15978732
TI  - Indirect evidence of submicroscopic pores in giant unilamellar [correction of
      unilamelar] vesicles.
AB  - Formation of pore-like structures in cell membranes could participate in exchange
      of matter between cell compartments and modify the lipid distribution between the
      leaflets of a bilayer. We present experiments on two model systems in which major
      lipid redistribution is attributed to few submicroscopic transient pores. The
      first kind of experiments consists in destabilizing the membrane of a giant
      unilamellar vesicle by inserting conic-shaped fluorescent lipids from the outer
      medium. The inserted lipids (10% of the vesicle lipids) should lead to membrane
      rupture if segregated on the outer leaflet. We show that a 5-nm diameter pore is
      sufficient to ease the stress on the membrane by redistributing the lipids. The
      second kind of experiments consists in forcing giant vesicles containing
      functionalized lipids to adhere. This adhesion leads to hemifusion (merging of
      the outer leaflets). In certain cases, the formation of pores in one of the
      vesicles is attested by contrast loss on this vesicle and redistribution of
      fluorescent labels between the leaflets. The kinetics of these phenomena is
      compatible with transient submicroscopic pores and long-lived membrane defects.

PMID- 15978733
TI  - In vitro binding of purified NahR regulatory protein with promoter Psal.
AB  - The NahR regulatory protein activates the naphthalene catabolic operon through
      binding to the Psal promoter in the presence of salicylate. Here, we investigated
      in vitro binding interaction between NahR and Psal using purified functional
      recombinant NahR. The T7-tagged NahR was shown to exist as a monomer in solution.
      Electrophoretic mobility shift assay (EMSA) showed that purified NahR bound to
      Psal in 3 different forms, whereas surface plasmon resonance (SPR) showed on an
      SPR chip at ratios ranging from 1:1 (at 0.42 microM NahR) to 8:1 (at 6.8 microM
      NahR). The binding was slightly inhibited by salicylate, suggesting that
      salicylate may not be involved in the binding of NahR to the promoter, but rather
      may be important in the activation of prebound NahR. An examination of the
      binding kinetics by SPR for the interaction between NahR and Psal revealed that
      the equilibrium dissociation constant was approximately 2.44 x 10(-6) M and the
      association and dissociation rates were 7.82 x 10(4) M(-1) s(-1) and 0.191 s(-1),
      respectively. These results demonstrate for the first time that purified NahR
      binds as a monomer to Psal and undergoes multimerization. In addition, we present
      novel data on the kinetics of NahR binding.

PMID- 15978734
TI  - Immunostimulation effects of proteose-peptone component 3 fragment on human
      hybridomas and peripheral blood lymphocytes.
AB  - Fat-free bovine milk fermented by 12 kinds of lactic acid bacteria and yeast
      enhanced monoclonal antibody production of human hybridoma HB4C5 cells 2.8-fold
      in serum-free medium. Immunoglobulin production of human peripheral blood
      lymphocytes (PBL) was also stimulated in vitro. IgM and IgG production of human
      PBL was accelerated up to 2.8-fold and 5.4-fold, respectively. Interferon-gamma
      production of human PBL was also accelerated 6.0-fold by 50 microg/ml of the
      fermented milk. However, interleukin-4 production of PBL was not affected, and
      tumor necrosis factor-alpha production was suppressed. The activity was enhanced
      2.5-fold by the thermal treatment for 30 min at 65 degrees C and was completely
      lost by trypsin digestion. The findings suggested that the active substance in
      the fermented milk was heat stable protein. Gel-filtration and the SDS-PAGE
      analysis revealed that the molecular weight of the active substance was estimated
      as 19.0 kDa, which was not detected in fat-free bovine milk before fermentation.
      N-terminal amino acid sequence of the 19.0 kDa protein was highly homologous to
      proteose-peptone component 3 (PP3). Since molecular weight of PP3 is 28 kDa, it
      is suggested that the 19.0 kDa protein is derived from degradation of PP3 during
      fermentation of fat-free milk. Moreover, PP3 purified from fat-free milk also
      enhanced IgM production of HB4C5 cells.

PMID- 15978735
TI  - Occurrence of a unique sialyl tetrasaccharide in colostrum of a bottlenose
      dolphin (Tursiops truncatus).
AB  - Crude oligosaccharides were recovered from bottlenose dolphin (Tursiops
      truncatus) colostrum after chloroform/methanol extraction of lipids and protein
      precipitation, and purified using gel filtration, anion exchange chromatography
      and high performance liquid chromatography (HPLC). Their chemical structures
      characterized by NMR spectroscopy were as follows: GalNAc(beta1-4)[Neu5Ac(alpha2
      3)]Gal(beta1-4)Glc, Neu5Ac(alpha2-3)Gal(beta1-4)Glc, Neu5Ac(alpha2-6)Gal(beta1
      4)Glc and Gal(alpha1-4)Gal(beta1-4)Glc. The monosialyltetrasaccharide and neutral
      trisaccharide have not previously been found as free forms in any natural sources
      including milk or colostrum, although these structures have been found in the
      carbohydrate units of glycosphingolipids GM2 and Gb3.

PMID- 15978736
TI  - Coincident stimulation of convergent cortical inputs enhances immediate early
      gene induction in the striatum.
AB  - The effect of coincident stimulation of convergent corticostriatal inputs was
      analyzed by the induction of immediate early genes in striatal neurons. Cortical
      motor areas were stimulated through implanted electrodes in awake, behaving rats,
      and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos
      and arc was analyzed in the striatum with in situ hybridization histochemistry.
      In the first experiment, unilateral stimulation of the medial agranular cortex,
      orofacial region of the lateral agranular cortex or the forelimb region of the
      lateral agranular cortex resulted in IEG induction in the striatum, which was
      restricted to the topographically related area receiving input from the
      stimulated cortical area. In a second experiment, stimulation parameters were
      altered, including frequency, number of pulses/train, and number of trains/s.
      These parameters did not have a significant effect on IEG induction. Notably, in
      some cases, in which there was IEG induction not only in the stimulated cortical
      region, but also in the homologous area in the contralateral hemisphere, very
      robust IEG induction was observed in the striatum. In a third experiment, the
      orofacial regions of the lateral agranular cortex of both hemispheres were
      stimulated coincidently. All of these animals showed robust striatal IEG
      induction. This IEG induction was attenuated by pretreatment with an NMDA
      antagonist MK-801. In a fourth experiment, we tested whether the coincidence of
      bilateral cortical stimulation contributed to the efficacy of striatal IEG
      induction. Either alternating stimulation or coincident stimulation of non
      homologous cortical regions produced significantly lower striatal IEG induction
      than obtained with coincident stimulation of homologous cortical areas. Enhanced
      striatal IEG induction occurred in indirect striatal neurons, labeled with
      enkephalin, but was also present in a large number of enkephalin-negative
      neurons, most of which are likely direct pathway neurons. These results suggest
      that regional and temporal convergence of cortical inputs enhances striatal IEG
      induction.

PMID- 15978737
TI  - Survival after attempted surgical resection and intraoperative radiation therapy
      for pancreatic and periampullary adenocarcinoma.
AB  - PURPOSE: To evaluate a single institution's experience with intraoperative
      radiation therapy (IORT) in combination with attempted surgical resection for
      pancreatic and periampullary adenocarcinoma. METHODS AND MATERIALS: From May 1986
      until June 2001, 77 patients at LDS Hospital underwent attempted surgical
      resection and IORT for pancreatic or periampullary adenocarcinoma. A potentially
      curative resection was defined as surgery with negative or microscopic positive
      margins. No patients had metastatic disease at the time of surgery and IORT.
      Forty-four patients with tumors located in the pancreas and 9 patients with
      periampullary tumors underwent potentially curative surgical resection and IORT.
      Twenty-four patients had pancreatic tumors deemed unresectable and underwent
      surgical bypass and IORT. Actuarial survival was calculated from the date of IORT
      until last follow-up or death by use of the Kaplan-Meier method. RESULTS:
      Patients undergoing a potentially curative resection and IORT for periampullary
      adenocarcinoma had a median survival of 167 months and a 56% 5-year actuarial
      survival, compared with a median survival of 16 months and a 19% 5-year actuarial
      survival for patients undergoing the same treatment for pancreatic adenocarcinoma
      (p = 0.03). Patients with unresectable disease who underwent bypass and IORT had
      a median survival of 11 months and a 0% 3-year survival, significantly worse than
      patients able to undergo surgical resection and IORT (p = 0.0002). The operative
      mortality for all patients undergoing potentially curative resection and IORT was
      3.7%. CONCLUSIONS: Intraoperative radiation therapy is well tolerated and does
      not increase the morbidity or mortality of potentially curative surgical
      resection for pancreatic or periampullary adenocarcinoma. Patients with
      periampullary adenocarcinoma have a better prognosis than those with pancreatic
      adenocarcinoma, and patients with unresectable pancreatic disease fared worse.

PMID- 15978738
TI  - Carotid artery stenosis in asymptomatic patients who have received unilateral
      head-and-neck irradiation.
AB  - PURPOSE: To determine the prevalence of carotid artery stenosis in patients who
      have received ipsilateral head-and-neck radiotherapy and have no symptoms of
      cerebrovascular disease. METHODS AND MATERIALS: Forty patients underwent
      ultrasound and computed tomography angiography of their carotid arteries. The
      vessels on the irradiated side were compared with those on the unirradiated side
      in a matched-pair analysis with regard to any stenosis, stenosis > or =60% in the
      internal carotid artery/carotid bulb, intima medial thickness (IMT), and grade of
      wall abnormalities. History, physical, and fasting blood levels were taken to
      detect risk factors for carotid disease. RESULTS: Fourteen irradiated carotid
      trees bore one or more stenosis vs. five in the unirradiated ones (p = 0.03).
      There were six bulb/internal carotid artery stenoses > or =60% in the irradiated
      carotids vs. one in the unirradiated (OR 6:1, p = 0.13). IMT and grade of vessel
      wall abnormality were higher in the irradiated carotids, but only at doses > or
      =50 Gy, and only at measurement points that lay within the radiation portals.
      CONCLUSION: Radiation appears to cause carotid artery stenosis. There may be a
      dose threshold for carotid wall changes, which has relevance for radiotherapy in
      several tumor sites.

PMID- 15978739
TI  - Genetic analyses for predictors of radiation response in glioblastoma.
AB  - PURPOSE: Radiotherapy (RT) for patients with glioblastoma improves survival and
      is recommended for nearly all patients with this diagnosis. However, the response
      to RT is variable in this patient population. Prior studies have suggested that
      underlying genetic alterations in the tumor may account for some of this
      treatment-related heterogeneity. It has been previously reported that epidermal
      growth factor receptor (EGFR) gene amplification and TP53 mutation correlate with
      the response to RT in patients with glioblastoma. METHODS AND MATERIALS: We
      sought to identify molecular markers that could predict the response to RT,
      progression-free survival after RT, and overall survival among 75 glioblastoma
      patients treated with RT at a single institution. Genetic analyses assessed EGFR
      amplification, TP53 mutations, CDKN2A/p16 deletion, and losses of chromosomes 1p,
      10q, and 19q. RESULTS: Unlike previous reports, no association of EGFR
      amplification with response to RT, progression-free survival, or overall survival
      was found. Moreover, no association was found between these endpoints and the
      other genetic alterations assayed (TP53 mutation, CDKN2A/p16 deletion, loss of
      heterozygosity 1p, loss of heterozygosity 10q, and loss of heterozygosity 19q).
      However, in accordance with recent observations that the prognostic effects of
      genetic alterations in glioblastoma may depend on patient age, we observed age
      dependent prognostic effects of TP53 and CDKN2A/p16 alterations in our patient
      population. For patients > or = 57 years old, those harboring TP53 mutations had
      a decreased overall survival compared with patients without TP53 mutations.
      Similarly, deletion of CDKN2A/p16 in patients > or = 57 years was associated with
      decreased progression-free survival after RT and a trend toward a shorter time to
      progression after RT compared with similar patients without the deletion.
      CONCLUSION: These data contrast with previous studies regarding the significant
      prognostic effect of EGFR with respect to RT response. Although our observations
      regarding the age-dependent prognostic effects of TP53 and CDKN2A/p16 are
      consistent with a prior report regarding these alterations, the present results
      should be considered preliminary, given the small sample size.

PMID- 15978740
TI  - Competing irradiation techniques for para-aortic lymph nodes: dose distribution
      and NTCP for the kidney.
AB  - PURPOSE: Partial coirradiation of both kidneys is an unavoidable consequence of
      adequate dose delivery in radiation therapy of para-aortic lymph nodes (PLN).
      Depending on total dose anteroposterior/posteroanterior (AP/PA), opposed-fields
      or multifield techniques are used. To optimize the treatment of potentially tumor
      affected PLN with minimal kidney involvement, we calculated normal tissue
      complication probabilities (NTCPs) of coirradiated kidneys for four common
      irradiation techniques used in the PLN area. METHODS AND MATERIALS: Planning
      target volume (PTV) delineation was performed in computed tomography scans of 21
      patients with a lateral safety margin of 3 cm from the aorta and 2 cm aside the
      vena cava. Ventral and dorsal margins of the PTV were delineated 2 cm from the
      vessels. As previously shown (Nevinny-Stickel M, et al. Int J Radiat Oncol Biol
      Phys 2000;48:147-151), PTVs optimized by these altered delineations permit
      inclusion of at least 97% of potentially involved PLN in contrast to standard
      delineations based on bony structures that are more likely to miss affected lymph
      nodes. The present study compared NTCPs for individual PTV-based treatment
      planning with NTCPs for standard planning based on bony structures. For each
      patient, four hypothetical treatment plans were created: (A) standard AP/PA
      opposed fields technique with lateral field margins along the tips of the
      transverse processes of the vertebral bodies; (B) individually planned AP/PA
      opposed fields with lateral field margins according to the optimized PTV; (C)
      standard four-field box technique with lateral width as described for (A), with
      dorsal borders at the center of the vertebral bodies and ventral margins 3 cm in
      front of the vertebrae; and (D) individually planned four-field box with lateral
      field margins according to the optimized PTV. Calculation of irradiation-induced
      complication probability values for nonuniform kidney irradiation was performed
      for model doses 19.8 Gy, 30.6 Gy, and 50.4 Gy according to the Lyman-Wolbarst
      model. RESULTS: No dose showed a statistically significant difference (p <
      0.00833, corrected for six multiple interrelated comparisons) in the median of
      total organ kidney NTCPs between techniques A, C, and D, with technique D
      intermediately ranging between technique A and C (e.g., for 50.4 Gy: A: median,
      0.39; range, 0.01-0.83; C: median, 0.27 range; 0.05-0.68; D: 0.36; range, 0.03
      0.72). In comparison to techniques A, C, and D, the individually planned AP/PA
      opposed-fields technique (B) was accompanied by significantly higher and
      intolerable overall kidney NTCP rates (e.g., for 50.4 Gy: median, 0.68; range,
      0.01-0.99). CONCLUSION: Conformal four-field planning with individually optimized
      PTVs (D) resulted in only moderate tissue complication probabilities in both
      kidneys with the advantage of providing significantly greater inclusion of
      potentially involved PLNs in comparison to accepted standard procedures (A and
      C).

PMID- 15978741
TI  - Utility of cranial boost in addition to total body irradiation in the treatment
      of high risk acute lymphoblastic leukemia.
AB  - PURPOSE: Total body irradiation (TBI) as part of a conditioning regimen before
      hematopoietic stem cell transplant (HSCT) is an important component in the
      management of acute lymphoblastic leukemia (ALL) that has relapsed or has other
      certain high-risk features. Controversy exists, however, as to whether a cranial
      boost in addition to TBI is necessary to prevent central nervous system (CNS)
      recurrences in these high-risk cases. Previous national trials have included a
      cranial boost in the absence of data to justify its use. Therefore, the aim of
      this study was to assess risk of CNS recurrence in ALL patients treated with TBI,
      to identify subsets of these high-risk patients at an increased or decreased risk
      of CNS recurrence after TBI, and to investigate whether regimens with higher
      doses of cranial irradiation further reduce the risk of CNS recurrence. METHODS
      AND MATERIALS: Charts of 67 consecutively treated patients with ALL who received
      TBI before HSCT were reviewed. Data including patient demographics, clinical
      features at presentation, conditioning regimen, donor source, use of a cranial
      boost, remission stage at transplant, histologic subtype, cytogenetics, and
      extramedullary site of presentation were retrospectively collected and correlated
      with the risk of subsequent CNS recurrence. RESULTS: At the time of analysis, 30
      (45%) patients were alive with no evidence of disease, 8 (12%) were alive with
      recurrence of leukemia, 7 (10.5%) had recurrent ALL but with successful salvage,
      7 (11%) died subsequent to recurrence, 14 (21%) died from complications related
      to HCST, and 1 patient was lost to follow-up (1.5%). Of the patients who recurred
      after HSCT, the relapses were hematologic in 13 (57%), CNS with or without
      simultaneous marrow involvement in 3 (13%), and other sites in 7 (30%). Forty-one
      (61%) patients did not receive an extracranial boost of irradiation with TBI. Two
      of these patients (4.9%) suffered CNS failures compared with 1 of 26 (3.8%) who
      received a cranial boost (p = 0.84). None of the 40 patients who presented only
      with hematologic disease developed a CNS recurrence despite the fact that only 13
      of 40 of these patients received a cranial boost after TBI. Cranial boost was
      therefore not associated with a reduction in CNS recurrence, especially in
      patients with only hematologic disease at presentation for which there were no
      failures regardless of the use of additional cranial radiotherapy. CONCLUSIONS:
      Patients who present with hematologic disease only at the time of HSCT have a low
      risk of CNS recurrence after TBI regardless of the use of a cranial boost,
      suggesting that a cranial boost may not be necessary in these patients.

PMID- 15978742
TI  - IMRT for adjuvant radiation in gastric cancer: a preferred plan?
AB  - PURPOSE: To assess the potential advantage of intensity-modulated radiotherapy
      (IMRT) over conformal planning for postoperative adjuvant radiotherapy in
      patients with gastric carcinoma. METHODS AND MATERIALS: Twenty patients who had
      undergone treatment planning with conformal beam arrangements for 4500 cGy
      adjuvant radiotherapy between 2000 and 2001 underwent repeat planning using IMRT
      techniques. Conformal five-field plans were compared with seven- to nine-field
      coplanar sliding-window IMRT plans. For each patient, the cumulative dose-volume
      histograms and organ-dose summaries (without distributions or digitally
      reconstructed radiographs) were provided to two independent, "blinded" GI
      radiation oncologists. The oncologists indicated which plan provided better
      planning target volume coverage and critical organ sparing, any safety concerns
      with either plan, and which plan they would choose to treat the patient. RESULTS:
      In 18 (90%) of 20 cases, both oncologists chose the same plan. Cases with
      disagreement were given to a third "blinded" reviewer. A "preferred plan" could
      be determined in 19 (95%) of 20 cases. IMRT was preferred in 17 (89%) of 19
      cases. In 4 (20%) of 20 IMRT plans at least one radiation oncologist had safety
      concerns because of the spinal cord dose (3 cases) or small bowel dose (2 cases).
      Of 42 ratings, IMRT was thought to provide better planning target volume coverage
      in 36 (86%) and better sparing of the spinal cord in 31 (74%) of 42, kidneys in
      29 (69%), liver in 30 (71%), and heart in 29 (69%) of 42 ratings. The median
      underdose volume (1.7 vs. 4.1 cm3), maximal dose to the spinal cord (36.85 vs.
      45.65 Gy), and dose to 50% of the liver (17.29 vs. 27.97), heart (12.89 vs. 15.50
      Gy), and left kidney (15.50 vs. 16.06 Gy) were lower with IMRT than with the
      conformal plans. CONCLUSION: Compared with the conformal plans, oncologists
      frequently preferred IMRT plans when using dose-volume histogram data. The
      advantages of IMRT plans include both improved planning target volume coverage
      and improved sparing of critical organs. We are currently studying organ motion
      in the upper abdomen as a prerequisite to using IMRT for actual patient
      treatment.

PMID- 15978743
TI  - Intensity-modulated radiation therapy (IMRT) of cancers of the head and neck:
      comparison of split-field and whole-field techniques.
AB  - BACKGROUND: Oropharynx cancers treated with intensity-modulated radiation (IMRT)
      are often treated with a monoisocentric or half-beam technique (HB). IMRT is
      delivered to the primary tumor and upper neck alone, while the lower neck is
      treated with a matching anterior beam. Because IMRT can treat the entire volume
      or whole field (WF), the primary aim of the study was to test the ability to plan
      cases using WF-IMRT while obtaining an optimal plan and acceptable dose
      distribution and also respecting normal critical structures. METHODS AND
      MATERIALS: Thirteen patients with early-stage oropharynx cancers had treatment
      plans created with HB-IMRT and WF-IMRT techniques. Plans were deemed acceptable
      if they met the planning guidelines (as defined or with minor violations) of the
      Radiation Therapy Oncology Group protocol H0022. Comparisons included coverage to
      the planning target volume (PTV) of the primary (PTV66) and subclinical disease
      (PTV54). We also compared the ability of both techniques to respect the tolerance
      of critical structures. RESULTS: The volume of PTV66 treated to >110% was less in
      9 of the 13 patients in the WF-IMRT plan as compared to the HB-IMRT plan. The
      calculated mean volume receiving >110% for all patients planned with WF-IMRT was
      9.3% (0.8%-25%) compared to 13.7% (2.7%-23.7%) with HB-IMRT (p = 0.09). The PTV54
      volume receiving >110% of dose was less in 10 of the 13 patients planned with WF
      IMRT compared to HB-IMRT. The mean doses to all critical structures except the
      larynx were comparable with each plan. The mean dose to the larynx was
      significantly less (p = 0.001), 18.7 Gy, with HB-IMRT compared to 47 Gy with WF
      IMRT. CONCLUSIONS: Regarding target volumes, acceptable plans can be generated
      with either WF-IMRT or HB-IMRT. WF-IMRT has an advantage if uncertainty at the
      match line is a concern, whereas HB-IMRT, particularly in cases not involving the
      base of tongue, can achieve much lower doses to the larynx.

PMID- 15978744
TI  - Profile of prognostic factors in 1022 Indian women with early-stage breast cancer
      treated with breast-conserving therapy.
AB  - PURPOSE: The outcome of breast cancer treatment can vary in different geographic
      and ethnic groups. A multivariate analysis was performed for various prognostic
      factors in 1022 Indian women with pathologic Stage I-II breast cancer treated
      between 1980 and 2000 with standard breast-conserving therapy with or without
      systemic adjuvant therapy. METHODS AND MATERIALS: At a mean follow-up of 53
      months, the outcomes studied were local failure, locoregional failure, and
      distant failure, overall survival (OS), and disease-free survival (DFS). RESULTS:
      The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph
      node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and
      DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or
      invasion (LVI) was the strongest independent adverse factor for all failure and
      survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83;
      OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node
      metastasis was also an independent adverse factor for local failure, locoregional
      failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence
      interval, 1.04-2.30). Age < or =40 years increased the incidence of local
      recurrence, and patients with inner quadrant tumors had inferior DFS. The
      incidence of LVI was significantly greater in women with lymph node metastases
      than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in
      those with Grade 1 or 2 tumors (p = 0.001). CONCLUSION: In Indian women, LVI was
      the strongest independent prognostic factor for OS, DFS, and local recurrence,
      irrespective of nodal status and systemic adjuvant treatment. Although LVI may
      not be a contraindication for BCT, as has been proposed by certain groups, it is
      necessary to define its role in prospective studies in determining local and
      systemic treatment.

PMID- 15978745
TI  - Conventional, conformal, and intensity-modulated radiation therapy treatment
      planning of external beam radiotherapy for cervical cancer: The impact of tumor
      regression.
AB  - PURPOSE: Investigating the impact of tumor regression on the dose within cervical
      tumors and surrounding organs, comparing conventional, conformal, and intensity
      modulated radiotherapy (IMRT) and the need for repeated treatment planning during
      irradiation. METHODS AND MATERIALS: Fourteen patients with cervical cancer
      underwent magnetic resonance (MR) imaging before treatment and once during
      treatment, after about 30 Gy. Target volumes and critical organs were delineated.
      First conventional, conformal, and IMRT plans were generated. To evaluate the
      impact of tumor regression, we calculated dose-volume histograms for these plans,
      using the delineations of the intratreatment MR images. Second conformal and IMRT
      plans were made based on the delineations of the intratreatment MR images. First
      and second plans were compared. RESULTS: The average volume receiving 95% of the
      prescribed dose (43 Gy) by the conventional, conformal, and IMRT plans was,
      respectively, for the bowel 626 cc, 427 cc, and 232 cc; for the rectum 101 cc, 90
      cc, and 60 cc; and for the bladder 89 cc, 70 cc, and 58 cc. The volumes of
      critical organs at this dose level were significantly reduced using IMRT compared
      with conventional and conformal planning (p < 0.02 in all cases). After having
      delivered about 30 Gy external beam radiation therapy, the primary gross tumor
      volumes decreased on average by 46% (range, 6.1-100%). The target volumes on the
      intratreatment MR images remained sufficiently covered by the 95% isodose. Second
      IMRT plans significantly diminished the treated bowel volume, if the primary
      gross tumor volumes decreased >30 cc. CONCLUSIONS: Intensity-modulated radiation
      therapy is superior in sparing of critical organs compared with conventional and
      conformal treatment, with adequate coverage of the target volumes. Intensity
      modulated radiation therapy remains superior after 30 Gy external beam radiation
      therapy, despite tumor regression and internal organ motion. Repeated IMRT
      planning can improve the sparing of the bowel and rectum in patients with
      substantial tumor regression.

PMID- 15978746
TI  - Reinvestigation of the proteolytically active components of Bromelia pinguin
      fruit.
AB  - Pinguinain is the name given to a proteolytic enzyme preparation obtained from
      Bromelia pinguin fruits that has been scarcely studied. The present paper deals
      on the reexamination of the proteases present in fruits of B. pinguin grown in
      Cienfuegos, Cuba. The preparation (partially purified pinguinain, PPP) showed the
      main characteristics of the cysteine proteases, i.e., optimum pH within alkaline
      range (pH 7.2-8.8), inhibition of proteolytic activity by thiol blocking
      reagents, which is usually reverted by addition of cysteine, a remarkable thermal
      stability and notable stability at high ionic strength values. Isoelectric
      focusing and zymogram of PPP revealed the presence of several proteolytic
      components between pI 4.6 and 8.1. Preliminary peptidase purification by cationic
      exchange chromatography showed the presence of two main proteolytic fractions
      with molecular masses of approximately 20.0 kDa, according to SDS-PAGE.

PMID- 15978747
TI  - Study of the mitochondrial transcription factor A (Tfam) gene in the primate
      Presbytis cristata.
AB  - The mitochondrial transcription factor A (Tfam) is a member of the HMG-box
      protein family, necessary for both transcription and maintenance of mitochondrial
      DNA. The gene is structured in seven exons and six introns and it is estimated to
      span about 10 kb in mouse, human and rat. In addition to the full length mRNA of
      Tfam, a shorter mRNA isoform lacking exon 5 has been found to be widely
      distributed in human and rat tissues. Here we present the isolation and
      characterization of Tfam gene in the primate Presbytis cristata which belongs to
      the Cercopithecidae family. We have determined the complete CDS sequence, the
      size of all the six introns, the complete sequences of the three shorter ones (I,
      III, VI) and the partial sequences of the long introns (II, IV, V). The
      comparison with other available Tfam sequences from mammals has revealed a high
      degree of conservation (above 90%) both in CDS and introns. By in situ
      hybridization (FISH) experiments we have mapped Tfam gene on chromosome 12 which,
      according to other cytogenetics studies, is the homologous region of chromosome
      10, where human Tfam has been mapped. Moreover we have searched for the presence
      of alternatively spliced isoforms through several approaches, such as RT-PCR and
      differential hybridization. In Presbytis cristata we have not detected the
      presence of any spliced isoforms lacking exons; however we have identified one
      isoform in which part of the intron I is retained in the mRNA. The inclusion of
      this portion of intron I would originate an early stop codon if translated.

PMID- 15978748
TI  - Lessons from a small, dispensable genome: the mitochondrial genome of yeast.
AB  - This article reviews the investigations on the mitochondrial genomes of yeast
      carried out in the author's laboratory during a quarter of a century (to be
      precise between 1966 and 1992). Our studies dealt with the structural basis for
      the cytoplasmic petite mutation, the replication, the transcription and the
      recombination of the mitochondrial genome, a genome which is dispensable and
      which comprises abundant non-coding sequences. This work led to some general
      conclusions on the nuclear genome of eukaryotes. Some recent results in apparent
      contradiction with our conclusions on ori sequences will also be briefly
      discussed.

PMID- 15978750
TI  - A soluble adenylyl cyclase from sea urchin spermatozoa.
AB  - A previously identified, calmodulin-binding, sea urchin sperm flagellar adenylyl
      cyclase (AC) was cloned and sequenced and found to be a homologue of mammalian
      sperm soluble adenylyl cyclase (sAC). Compared to the mammalian sAC, the sea
      urchin sAC (susAC) has several long amino acid insertions, some of which contain
      protein kinase A phosphorylation sites. The enzymatic activity of susAC shows a
      steep pH dependency curve, the specific activity doubling when the pH is
      increased from 7.0 to 7.5. This suggests that like sperm dynein ATPase, the susAC
      is probably activated by increases in intracellular pH occurring upon spawning
      into seawater and also when sperm respond to contact with the egg jelly layer.
      The susAC is strongly activated by manganese, but has low activity in magnesium.
      Gene database searches identified sAC homologues in species known to have cyclic
      AMP-dependent sperm motility. This implies (as shown in mouse) that susAC has a
      role in sperm motility, most probably through axonemal protein phosphorylation or
      ion channel regulation.

PMID- 15978749
TI  - Mitochondria-to-nucleus stress signaling in mammalian cells: nature of nuclear
      gene targets, transcription regulation, and induced resistance to apoptosis.
AB  - Depletion of mitochondrial DNA (mtDNA) or treatment with mitochondrial poison
      CCCP initiates mitochondrial stress signaling, which operates through altered
      Ca2+ homeostasis. In C2C12 rhabdomyoblasts and A549 human lung carcinoma cells
      mitochondrial stress signaling activates calcineurin and a number of Ca2+
      responsive factors including ATF, NFAT, CEBP/delta and CREB. Additionally, PKC
      and MAP kinase are also activated. A number of nuclear gene targets including
      those involved in Ca2+ storage/release (RyR1, calreticulin, calsequestrin),
      glucose metabolism (hexokinase, pyruvate kinase, Glut4), oncogenesis (TGFbeta1,
      cathepsin L, IGFR1, melanoma antigen) and apoptosis (Bcl-2, Bid, Bad, p53) are
      upregulated. Mitochondrial stress in both C2C12 myoblasts and A549 cells induced
      morphological changes and invasive phenotypes. These cells also showed markedly
      increased resistance to etoposide-induced apoptosis that is a hallmark of highly
      invasive tumors. Our results describe a new mechanism of altered nuclear gene
      expression and phenotypic changes triggered by mitochondrial dysfunction and
      mtDNA damage.

PMID- 15978751
TI  - Rapid divergency of rodent CD99 orthologs: implications for the evolution of the
      pseudoautosomal region.
AB  - The human pseudoautosomal region 1 (PAR1) is essential for the obligatory X-Y
      crossover in male meiosis. Despite its critical role, comparative studies of
      human and mouse pseudoautosomal genes have been limited owing to the scarcity of
      genes conserved between the two species. Human CD99 is a 32-kDa cell surface
      protein that is encoded by the MIC2 gene localized to the PAR1. Although several
      sequences such as CD99L2, PBDX, and CD99L1 are related to CD99, its murine
      ortholog, Cd99, has not yet been identified. Here we report a novel mouse Cd99,
      designated D4, which shows overall sequence homology to CD99, with the highest
      conservation between the two genes being found in the transmembrane regions. In
      addition, the D4 protein displays biochemical characteristics, functional
      homology, and expression patterns similar to those of CD99. The D4 gene is
      localized on an autosome, chromosome 4, reflecting a common mapping feature with
      other mouse orthologs of human PAR1 genes. Furthermore, a phylogenetic analysis
      of CD99-related genes confirmed that the D4 gene is indeed an ortholog of CD99
      and exhibits the accelerated evolution pattern of CD99 orthologs, as compared to
      the CD99L2 orthologs. On the basis of these findings, we suggest that CD99
      belongs to the ancient PAR genes, and that the rapid interspecies divergence of
      its present sequence and map position is due to a high recombination frequency
      and the occurrence of chromosomal translocation, supporting the addition
      attrition hypothesis for PAR evolution.

PMID- 15978752
TI  - Effect of non-esterified fatty acids on bovine theca cell steroidogenesis and
      proliferation in vitro.
AB  - Elevated serum non-esterified fatty acid (NEFA) levels associated with a negative
      energy balance (NEB) may affect ovarian function and hence reproductive
      performance in high-yielding dairy cows. We have investigated the individual and
      combined effects of the three major NEFAs on bovine theca cell proliferation and
      steroidogenesis in vitro. Theca cells from healthy large follicles (>8 mm)
      obtained from slaughterhouse ovaries were cultured in serum free medium in the
      presence of 0, 50, 150 and 200 microM of palmitic acid (PA; C16:0); 0, 50, 150
      and 250 microM of stearic acid (SA; C18:0); and/or 0, 50, 150 and 250 microM of
      oleic acid (OA; C18:1). Progesterone and androstenedione concentrations were
      measured in spent medium after 48 h of culture and cell numbers were determined
      spectrophotometrically per culture well. Cell viability was assessed by annexin-V
      FITC/propidium iodide staining. Only the treatment with 200 microM of PA
      inhibited cell proliferation (P<0.001) when tested individually, both of the
      mixtures tested (M1=100 microM of PA, 130 microM of SA and 140 microM of OA;
      M2=200 microM PA, 260 microM of SA and 280 microM of OA) reduced cell numbers
      (P<0.001). Progesterone and androstenedione production, both per well and per
      10(4) cells, were not affected by any of the treatments, with the exception of
      M2. This mixture reduced progesterone production per well and per 10(4) cells
      (P<0.05). The effects observed were most likely caused by the cytotoxic action of
      the NEFAs, as demonstrated by the increased percentage of early apoptotic (M1)
      and late apoptotic/necrotic cells (M1 and M2) in the combination treatments
      (P<0.05). When combined, elevated physiological concentrations of PA, SA and OA
      can modulate theca cell proliferation and steroidogenesis in vitro by reducing
      theca cell viability. These NEFAs may be one of the mediators through which NEB
      compromises ovarian functioning and thus fertility in high-yielding dairy cows.

PMID- 15978753
TI  - Effects of four different regimens of hormone replacement therapy on hemostatic
      parameters: a prospective randomized study.
AB  - OBJECTIVE: To compare the effects of four different regimens including oral and
      transdermal formulations with or without progestins on the hemostatic system in a
      prospective randomized fashion. METHODS: Eighty-eight women were randomized to
      four groups receiving continuous transdermal estradiol 50 microg/day (tE2), oral
      conjugated equine estrogen 0.625 mg/day (CEE 0.625 mg), oral conjugated equine
      estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day (CEE 0.625
      mg/MPA 2.5 mg), or oral 2 mg 17-beta estradiol combined with 1 mg norethistrone
      acetate (E2/norethistrone). The hysterectomized patients received only estrogen,
      and the remaining women received the estrogen plus progesterone combination
      regimens. As a marker of hemostatic system fibrinogen, tissue plasminogen
      activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were
      measured initially, and after 1 and 6 months of therapy. RESULTS: The treatment
      groups were well matched for baseline characteristics including age, height,
      weight, body mass index, and systolic and diastolic blood pressures. During the
      study period fibrinogen levels were below the baseline values in all groups.
      However, the decrease was only statistically significant in patients treated with
      oral 0.625 mg/day CEE. tPA levels were decreased significantly by tE2, CEE 0.625
      mg, and CEE 0.625 mg/MPA 2.5 mg. PAI-1 levels were decreased significantly by CEE
      0.625 mg, and CEE 0.625 mg/MPA 2.5 mg. When the effects of the four different
      regimens were compared using percentage changes from the baseline, no significant
      difference was found among the treatment groups. CONCLUSION: One of the treatment
      regimens resulted in a more coagulable state. Oral therapy with CEE decreased the
      levels of all parameters, and MPA did not impair this beneficial effect, except
      for in fibrinogen. Transdermal therapy had a minimal effect. No significant
      difference was noted among the four regimens.

PMID- 15978754
TI  - Cholesteryl hemisuccinate as a membrane stabilizer in
      dipalmitoylphosphatidylcholine liposomes containing saikosaponin-d.
AB  - In the present study, cholesteryl hemisuccinate (CHEMS) was evaluated for use as
      a membrane stabilizer in dipalmitoylphosphatidylcholine (DPPC) liposomes.
      Differential scanning calorimetry (DSC) and a calcein release study showed that
      CHEMS was more effective than cholesterol (CHOL) in increasing DPPC membrane
      stability. The findings of Fourier transform infrared spectroscopy (FT-IR) also
      suggested that CHEMS interacts with DPPC via both hydrogen bonding and
      electrostatic interaction. More importantly, CHEMS did not interact with
      saikosaponin-d (SSD), a triterpene saponin from Bupleurum species, unlike CHOL.
      SSD-containing liposomes with DPPC, CHEMS and DSPE-PEG could greatly decrease the
      hemolytic activity of SSD. This study demonstrated that CHEMS has more
      stabilization ability than CHOL since CHEMS may exhibit both hydrogen bond
      interaction and electrostatic interaction with DPPC membrane while CHOL only has
      hydrogen bond interaction, resulting in stable and low-hemolytic SSD-liposomes.

PMID- 15978755
TI  - Technical aspects of the production of dried extract of Maytenus ilicifolia
      leaves by jet spouted bed drying.
AB  - This work presents an evaluation of the performance of jet spouted bed with inert
      particles for production of dried extracts of Maytenus ilicifolia leaves. The
      development of the extraction procedure was carried-out with the aid of three
      factors and three levels Box-Behnken design. The effects of the extraction
      variables, temperature (Text); stirring time (theta); and the ratio of the plant
      to solvent mass (m(p)/m(s)) on the extraction yield were investigated. The drying
      performance and product properties were evaluated through the measurement of the
      product size distribution, loss on drying (Up), flavonoid degradation (D) and,
      process thermal efficiency (eta). These parameters were measured as a function of
      the inlet temperature of the spouting gas (Tgi), the feed mass flow rate of the
      concentrated extract relative to mass flow rate of the spouting gas (Ws/Wg), the
      ratio between the feed flow rate of spouting gas relative to feed flow rate at a
      minimum spouting condition (Q/Qms) and the static bed height (H0). A powder
      product with a low degradation of active substances and good physical properties
      were obtained for selected operating conditions. These results indicate the
      feasibility of this drying equipment for the production of dried extracts of M.
      ilicifolia Martius ex Reiss leaves.

PMID- 15978756
TI  - The role of Fas-mediated apoptosis in otitis media: observations in the lpr/lpr
      mouse.
AB  - Apoptosis, or programmed cell death, is a critical regulatory mechanism involved
      in the function, homeostasis and stimulus response of many organ systems. In the
      middle ear, apoptosis could participate in mucosal remodeling or leukocyte
      clearance during otitis media (OM). Fas is a death receptor that can contribute
      to apoptosis in a variety of cell types. To assess the role of Fas signaling in
      OM, we probed for expression of Fas and Fas ligand (FasL) by polymerase chain
      reaction (PCR) during bacterial OM in the rat. In addition, we assessed the
      response of the middle ear to endotoxin, an inflammatory bacterial product that
      has been used as a model for otitis media in the mouse, in normal and Fas
      deficient mice. We saw evidence of increased expression of Fas and Fas ligand
      during bacterial OM. Moreover, the intensity of the mucosal response to endotoxin
      was significantly greater and the resolution of the response was prolonged in Fas
      deficient mice. Prolonged resolution of mucosal hyperplasia may reflect reduced
      apoptosis of the hyperplastic mucosal cells. Elucidation of the pathways that
      regulate the mucosal hyperplastic response during otitis media brings us closer
      to manipulating them in the interest of reducing the chronic complications of
      this disease.

PMID- 15978757
TI  - Traditional pharmacopoeias and medicines among Albanians and Italians in southern
      Italy: a comparison.
AB  - A cross-cultural comparison of traditional household remedies in primary health
      care and ritual healing practices in two economically and socio-demographically
      similar communities in Lucania (inland southern Italy) was considered:
      Ginestra/Zhure, inhabited by ethnic Albanians, who migrated to the area during
      the 15th century, and Castelmezzano, inhabited by autochthonous South-Italians.
      In Ginestra/Zhure, the number of traditional natural remedies (mainly derived
      from local medicinal plants) was only half of that in the local folk
      pharmacopoeia quoted in Castelmezzano. However, ritual magic-healing practices
      still play a central role among the Albanians in Ginestra/Zhure, while they do
      not in Castelmezzano. Reasons for this shift, as well as components that have
      affected cultural adaptation phenomena and transitions among the Albanians are
      discussed.

PMID- 15978758
TI  - In vitro antimicrobial activity of extracts of four Achillea species: the
      composition of Achillea clavennae L. (Asteraceae) extract.
AB  - The extracts of aerial parts of Achillea clavennae, Achillea holosericea,
      Achillea lingulata and Achillea millefolium (hexane:ether:methanol=1:1:1) have
      been tested for antimicrobial activity in a disk diffusion assay against five
      bacteria (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae,
      Pseudomonas aeruginosa and Salmonella enteritidis) and two fungi (Aspergillus
      niger and Candida albicans). Extracts of all four species possessed a broad
      spectrum of antimicrobial activity against all tested strains. The composition of
      the extract of Achillea clavennae, which showed the strongest activity, was
      investigated and the structures of isolated compounds were elucidated by spectral
      means (1D and 2D NMR, UV, IR and MS). The extract yielded alkanes, fatty acids,
      monoterpenes, guaiane sesquiterpenes (rupicolin A and B, 1-deoxy-1alpha-peroxy
      rupicolin A and B), and flavonoids (apigenin and centaureidin). This study
      confirms the ethnopharmacological use of plants from this genus and places
      Achillea clavennae L. on the same level as the recognized Achillea millefolium.

PMID- 15978759
TI  - Perspectives of ethnopharmacology.

PMID- 15978760
TI  - A history of the therapeutic use of liquorice in Europe.
AB  - Liquorice root has been used in Europe since prehistoric times, and is well
      documented in written form starting with the ancient Greeks. In this review we
      compare the independent development of medical uses of this botanical drug in
      several ancient cultures, attempting to show the rationality of specific
      indications across different ethnic groups with different cultural backgrounds.
      Identical specific indications in different cultures highlight universally
      reproducible therapeutic effects that are beyond those of a mere placebo. In the
      first part of the review, historical sources dealing with liquorice (Scythian,
      Greek, Roman, and from the Middle Ages in Germany, Italy, Spain, England) have
      been considered. In the second part, the historical records of diseases treated
      with liquorice have been presented. Finally, a comparison between traditional use
      in and outside Europe, with the most important recent scientific studies
      concerning its use, is presented.

PMID- 15978761
TI  - Exhumation examination to confirm suspicion of fatal lead poisoning.
AB  - Acute poisonings with inorganic lead compounds are exceptionally rare. In all
      cases of diagnosis, there are two possible sources of error: failing to recognise
      lead poisoning when it is present, and mistaking other diseases for lead
      poisoning. If exposure history is carefully taken and proper laboratory
      techniques are employed, the diagnosis of lead poisoning should not be difficult.
      In the described case of the death of a 41-year-old-man, no enzymatic
      disturbances characteristic of congenital erythropoietic porphyria were
      ascertained, and furthermore, a considerable concentration of lead was found in
      antemortem material, 5 months before death (blood: 1584 microg/l, urine: 531
      microg/24 h). Postmortem tissue lead content in the biological material, exhumed
      6 months after death, were as follows: liver, 47.6 microg/g; kidney, 4.75
      microg/g; bone, 103 microg/g of sacral vertebra, 20.4 microg/g of femoral bone,
      112 microg/g of pelvis; hair, 30.2 microg/g of scalp hair, 33.7 microg/g of pubic
      hair; nails, 13.6 microg/g. The results indicated a case of acute lead poisoning
      (with lead(II) oxide, as it later turned out), which manifested as acute
      intermittent porphyria.

PMID- 15978762
TI  - Two simultaneous suicidal gunshots to the head with robbed police guns.
AB  - The suicidal infliction of two gunshot wounds to the head represents a critical
      issue for medicolegal investigation. In principle, simultaneous infliction with
      two firearms or third parties' involvement, i.e. two consecutive gunshots, have
      to be considered. We report for the first time on a case of suicidal infliction
      of two simultaneous gunshots to the head (oral, temporal) with Action 4 expanding
      ammunition. A male had robbed two service guns and committed suicide thereafter
      under the influence of high-dose alcohol and cocaine. Interestingly, Action 4
      ammunition had been used, leading to an uncommon gunshot wound morphology and
      extensive backspatter. At the scene, these findings caused confusion; moreover,
      the number of gunshot wounds was unclear, until autopsy revealed two gunshot
      wounds to the head, which had obviously been inflicted simultaneously. Expanding
      ammunition like QD-PEP and Action 4, used by several German federal state police
      forces, can cause an atypical gunshot wound morphology, most probably due to its
      peculiar deformation behaviour. Investigators should be careful when interpreting
      gunshot wound morphology at the scene after usage of such expanding ammunition.
      With regard to reconstruction in cases of two gunshot wounds to the head and two
      guns at the scene, two simultaneous gunshots should be taken into consideration.

PMID- 15978763
TI  - Y-chromosome STR haplotypes in Sweden.
AB  - A total of 708 men, with Swedish names, from different parts of Sweden have been
      typed for the Y-chromosome minimal haplotype STR markers DYS19, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393 and DYS385. Of these, 403 men were of
      geographically undefined Swedish origin and the rest, 305, from seven defined
      geographical regions. PCR-products were detected by ABI377 using sequenced
      allelic ladders. An evaluation of the 708 chromosomes revealed 423 different
      haplotypes. Only 100 of the haplotypes were found more than once. The over all
      haplotype diversity was 0.994. The haplotype 14, 12, 28, 23, 10, 11, 13, 14-14
      has the highest frequency of 5.79% and is significantly Swedish, when compared to
      other European populations.

PMID- 15978764
TI  - Evaluation of quantitative CT indexes in idiopathic interstitial pneumonitis
      using a low-dose technique.
AB  - OBJECTIVE: To evaluate and compare histogram features (mean lung attenuation,
      skewness, kurtosis) of low-dose and standard-dose CT in a group of patients
      affected by idiopathic interstitial pneumonitis. METHODS: We analyzed 16 patients
      affected by idiopathic interstitial pneumonitis. Spiral whole lung thin-section
      CT acquisition at standard dose (100 mAs) and three additional low-dose (50 mAs)
      CT images were obtained. After obtained frequency histograms, mean lung
      attenuation (MLA), skewness and kurtosis and three range of density (-700/-200
      HU; -700/-400 HU; -500/-200 HU) of the standard-and low-dose thin-section CT
      scans were analyzed and compared. RESULTS: The parameters obtained with low-dose
      and standard-dose spiral CT were correlated in a highly significant manner and
      were equivalent (p<0.01). The greatest correlation was found between standard-and
      low-dose kurtosis and standard and low-dose -700/-400 HU subrange of density
      (r=0.92; p<0.0001). CONCLUSIONS: Our results prove that a quantitative CT
      objective evaluation in lung fibrosis can be successfully obtained with low-dose
      spiral CT, with reduced mA.

PMID- 15978765
TI  - Dose reduction in maxillofacial imaging using low dose Cone Beam CT.
AB  - OBJECTIVES: (a) To measure the absorbed dose at certain anatomical sites of a
      RANDO phantom and to estimate the effective dose in radiographic imaging of the
      jaws using low dose Cone Beam computed tomography (CBCT) and (b) to compare the
      absorbed and the effective doses between thyroid and cervical spine shielding and
      non-shielding techniques. STUDY DESIGN: Thermoluminescent dosimeters (TLD-100)
      were placed at 14 sites in a RANDO phantom, using a Cone Beam CT device (Newtom,
      Model QR-DVT 9000, Verona, Italy). Dosimetry was carried out applying two
      techniques: in the first, there was no shielding device used while in the second
      one, a shielding device (EUREKA!, TRIX) was applied for protection of the thyroid
      gland and the cervical spine. Effective dose was estimated according to ICRP(60)
      report (E(ICRP)). An additional estimation of the effective dose was accomplished
      including the doses of the salivary glands (E(SAL)). A Wilcoxon Signed Ranks Test
      was used for statistical analysis. RESULTS: In the non-shielding technique the
      absorbed doses ranged from 0.16 to 1.67 mGy, while 0.32 and 1.28 mGy were the
      doses to the thyroid and the cervical spine, respectively. The effective dose,
      E(ICRP), was 0.035 mSv and the E(SAL) was 0.064 mSv. In the shielding technique,
      the absorbed doses ranged from 0.09 to 1.64 mGy, while 0.18 and 0.95 mGy were the
      respective values for the thyroid and the cervical spine. The effective dose,
      E(ICRP), was 0.023 mSv and E(SAL) was 0.052 mSv. CONCLUSIONS: The use of CBCT for
      maxillofacial imaging results in a reduced absorbed and effective dose. The use
      of lead shielding leads to a further reduction of the absorbed doses of thyroid
      and cervical spine, as well as the effective dose.

PMID- 15978766
TI  - HPLC determination of salinomycin and related compounds in fermentation media of
      Streptomyces albus and premixes.
AB  - A rapid, sensitive and selective HPLC method with post-column derivatization was
      proposed for the determination of salinomycin and related products in
      fermentation broths and premixes. The solvent extracts of samples were analysed
      on a reversed-phase monolithic type column. The mobile phase consisted of
      methanol/zinc acetate (0.05 M) adjusted to pH 4.0 with acetic acid (85/15, v/v).
      Post-column derivatization with vanillin at 85 degrees C was used for
      simultaneous, selective detection of salinomycin at 520 nm and related products
      at 460 nm. Optimal ratio of mobile phase/reagent flow rate was 2:1.
      Alternatively, pre-column derivatization of salinomycin and related products with
      three different reagents (2,4-dinitrophenylhydrazine, p-bromophenacyl bromide and
      p-nitrobenzoyl chloride) was examined. Suitable derivates for HPLC separation and
      UV detection were prepared using p-nitrobenzoyl chloride. Extraction ability of
      various solvents for extracting of salinomycin and co-products from premix
      samples was also tested. Acetone, ethanol and pyridine were found to be the best
      extraction solvents for these compounds.

PMID- 15978768
TI  - A novel high-throughput automated chip-based nanoelectrospray tandem mass
      spectrometric method for PAMPA sample analysis.
AB  - Parallel artificial membrane permeability assay (PAMPA) has recently gained
      popularity as a novel, high-throughput assay capable of rapidly screening
      compounds for their permeability characteristics in early drug discovery. The
      analytical techniques typically used for PAMPA sample analysis are HPLC-UV, LC/MS
      or more recently UV-plate reader. The LC techniques, though sturdy and accurate,
      are often labor and time intensive and are not ideal for high-throughput. On the
      other hand, UV-plate reader technique is amenable to high-throughput but is not
      sensitive enough to detect the lower concentrations that are often encountered in
      early drug discovery work. This article investigates a novel analytical method, a
      chip-based automated nanoelectrospray mass spectrometric method for its ability
      to rapidly analyze PAMPA permeability samples. The utility and advantages of this
      novel analytical method is demonstrated by comparing PAMPA permeability values
      obtained from nanoelectrospray to those from conventional analytical methods. Ten
      marketed drugs having a broad range of structural space, physico-chemical
      properties and extent of intestinal absorption were selected as test compounds
      for this investigation. PAMPA permeability and recovery experiments were
      conducted with model compounds followed by analysis by UV-plate reader, UV-HPLC
      as well as the automated nanoelectrospray technique (nanoESI-MS/MS). There was a
      very good correlation (r(2) > 0.9) between the results obtained using
      nanoelectrospray and the other analytical techniques tested. Moreover, the
      nanoelectrospray approach presented several advantages over the standard
      techniques such as higher sensitivity and ability to detect individual compounds
      in cassette studies, making it an attractive high-throughput analytical
      technique. Thus, it has been demonstrated that nanoelectrospray analysis provides
      a highly efficient and accurate analytical methodology to analyze PAMPA samples
      generated in early drug discovery.

PMID- 15978767
TI  - Mechanistic explanation to the catalysis by pyrazinamide and ethambutol of
      reaction between rifampicin and isoniazid in anti-TB FDCs.
AB  - Rifampicin and isoniazid are known to interact with each other in solid
      formulation environment to yield isonicotinyl hydrazone (HYD). In earlier
      studies, this reaction was indicated to be catalyzed by pyrazinamide and
      ethambutol hydrochloride, the two other co-drugs present in oral anti
      tuberculosis fixed-dose combination (FDC) formulations. Accordingly, the present
      study was carried out to understand the catalytic role of pyrazinamide and
      ethambutol hydrochloride on the reaction between rifampicin and isoniazid. For
      the purpose, organic bases and amides similar in structure to pyrazinamide and
      ethambutol hydrochloride were combined individually with rifampicin and
      isoniazid. The compounds employed were pyrazine, piperdine, pyrollidine,
      pyridine, triethylamine, diisopropylethylamine, picolinamide, benzamide,
      ethylenediamine, ethanolamine, diethanolamine, and triethanolamine. An additional
      study was also carried out in the presence of free base of ethambutol. The
      mixtures were exposed to accelerated stability test condition of 40 degrees C/75%
      RH for 15 d. The nature of the products formed and the changes in relative
      concentrations of the drugs and products were followed by HPLC. The drugs showed
      different extent of degradation, yielding HYD, and in some cases degradation
      products of rifampicin. The results confirmed the catalytic role of pyrazinamide
      and ethambutol hydrochloride. The catalysis is postulated to involve intra
      molecular proton transfer during transhydrazone formation process, entailing a
      tetrahedral mechanism.

PMID- 15978769
TI  - Spectrophotometric method for polyphenols analysis: prevalidation and application
      on Plantago L. species.
AB  - The prevalidation strategy was applied to evaluate UV-vis spectrophotometric
      procedure with Folin-Ciocalteu's reagent for polyphenols determination.
      Favourable prevalidation characteristics verified this procedure as a valuable
      tool in polyphenols analysis and it was successfully applied for determination of
      total polyphenols and tannins in leaves, stems and flowers of Plantago L. species
      growing in Croatia. The results showed the variety of total polyphenols content
      between different plant parts (leaves: up to 10.15%; stems: up to 4.34% and
      flowers: up to 5.56%). The content of tannins in stems was from 0.28% to 1.00%,
      while leaves and flowers contained tannins in concentrations of 2.26% and 2.21%,
      respectively. The results of polyphenols determination were evaluated by using
      multivariate analysis (UPGMA and PCA) as a contribution to elucidation of
      relations between different taxa of genus Plantago L.

PMID- 15978770
TI  - Effects of food processing on the stability of food allergens.
AB  - The ubiquitous presence of allergens in the human food supply coupled with
      increased awareness of food allergies warrants undertaking appropriate preventive
      measures to protect sensitive consumers from unwanted exposure to offending food
      allergens. Attempts to reduce or eliminate food allergenicity through food
      processing have met with mixed results. The rationale for using food processing
      to reduce/eliminate allergenicity and limitations to using this approach are
      discussed.

PMID- 15978771
TI  - Neurotrophins in murine viscera: a dynamic pattern from birth to adulthood.
AB  - There is growing evidence that target-derived neurotrophins regulate the function
      of visceral neurons after birth. However, the postnatal profile of neurotrophin
      supply from internal organs is poorly described. In this study, we compared
      neurotrophin concentrations in lysates of murine peripheral target tissues (lung,
      heart, liver, colon, spleen, thymus, kidney and urinary bladder) at different
      time points after birth. In most organs, there was a decrease of neurotrophin
      concentrations in the first weeks after birth. In contrast, there were
      characteristic increases of specific neurotrophins during adolescence or
      adulthood. These increases were found for nerve growth factor (NGF) in the heart,
      thymus, kidney and liver, for brain-derived neurotrophic factor (BDNF) in the
      lung, and for neurotrophin-3 (NT-3) in the colon. In conclusion, we show that
      neurotrophins display a very differential and dynamic profile in internal organs
      after birth.

PMID- 15978772
TI  - Fine mapping of radiation susceptibility and gene expression analysis of LEC
      congenic rat lines.
AB  - LEC rats constitute an animal model of high susceptibility to X-rays. We
      developed congenic LEC rat lines (recipient strain, Fischer 344 (F344)) and
      performed genome-wide genotyping to identify radiation susceptibility genes. We
      mapped seven positional candidate genes, Bmp10, Gpr73, Gp9, Cnbp, Copg, Rab7, and
      Rpn1, to an approximately 1.2-Mb region located between loci D4Got85 and D4Got148
      on chromosome 4. None of the seven genes has been reported to be associated with
      radiation susceptibility. Comparison of the coding sequences for these seven
      genes in F344 and LEC rats showed no changes in deduced amino acid sequences. We
      determined gene expression differences in Gp73, Gp9, and Cnbp as well as strain
      specific variations in upstream sequences of these genes. Our results suggest
      that radiation susceptibility in the LEC rat is primarily attributable to one of
      the genes within this approximately 1.2-Mb region; however, expression analysis
      gave no clear indication as to which gene is responsible.

PMID- 15978773
TI  - Post-marketing surveillance system for drugs in pregnancy--15 years experience of
      ENTIS.
AB  - Teratology Information Services (TIS) provide the public and health professionals
      with tailor-made information on drug risks in pregnancy. TIS in Europe, Israel
      and Latin America collaborate in the European Network of Teratology Information
      Services (ENTIS) in order to optimise interpretation of risk data, risk
      communication and risk management as well as recommendations for drug treatment
      in pregnant women. In addition, efforts are undertaken to enhance and harmonise
      documentation of exposed pregnancies and their outcomes. These prospectively
      ascertained data are evaluated like controlled, observational cohort studies,
      where exposed pregnancies are compared to a non-exposed control group for various
      outcome variables such as (major) malformations, birth measures and the state of
      the new-born infant, spontaneous abortion. The prospective methodology minimises
      recall bias of the studied drugs. Evaluating the data collected according to
      standardised protocols with appropriate statisticals methods substantially
      improves risk assessment. The comparison of spontaneous abortions between
      coumarin exposed pregnancies and controls enrolled in the Berlin TIS demonstrates
      the benefit of the methodology of survival analysis within the framework of the
      proportional hazard model. The ENTIS multi-centre approach permits studying large
      exposed cohorts even with seldomly used medicinal products. In terms of post
      marketing surveillance there are no alternatives to TIS data. Data collection by
      TIS uses an already established risk communication system, and has the advantage
      of low costs and motivated responders. As a TIS is contacted mainly for
      insufficiently documented drugs or those suspected of acting as developmental
      toxicants there is even a selection for products needing research.

PMID- 15978774
TI  - Folic acid--the scientific debate as a base for public health policy.
AB  - Randomized controlled trials have proven that periconceptional folic acid intake
      reduces the risk of neural tube defects (NTDs). This lead to different public
      health policies: fortification of foods in many countries and supplementation in
      some others. We concentrate here on pro's and con's of fortification policies.
      Meanwhile, new beneficial but also potential adverse effects are being
      hypothesized. Highest level evidence is available for the protective effect of
      folic acid on NTDs. Lower level evidence suggests other protective effects, but
      also some potential adverse effects, such as masking Vitamin B-12 deficiency,
      increasing twinning rates and an 'acceleration phenomenon' in pre-existing
      malignant neoplasms. While observational studies show lower cancer rates
      associated with increased folate intake, some case reports and animal experiments
      suggest opposite effects. Thus, public health policy makers are facing the
      question of balancing beneficial and potential adverse effects repeatedly. We
      propose that the scientific debate no longer focuses on NTDs alone, but that a
      comprehensive evaluation be undertaken by a public health authority with
      experience in complex meta-analyses and technology assessment.

PMID- 15978775
TI  - Onlay augmentation versus sinuslift procedure in the treatment of the severely
      resorbed maxilla: a 5-year comparative longitudinal study.
AB  - Augmentation procedures in the severely resorbed maxilla are standard techniques
      in preprosthetic surgery. Aim of the present study was to compare onlay bone
      grafting and sinus floor elevation with autogenous bone grafts in edentulous
      patients in terms of bone resorption of the posterior alveolar crest and implant
      survival in a 5-year longitudinal study. A total of 100 patients (53 female and
      47 male patients) requiring augmentation using autogenous bone due to a severely
      resorbed maxillae were evaluated. The degree of resorption and bone quality were
      preoperatively estimated in panoramic radiographs according to Lekholm and Zarb.
      The overall 5-year success rate of implants placed after augmentation procedures
      in the posterior maxilla was 93.1%. Following onlay augmentations 215 out of 235
      implant insertions were successful, i.e. a success rate of 91.5% was achieved. In
      the sinuslift group, 330 out 349 implants remained successful, i.e. a success
      rate of 94.6% was found. The difference between both groups was statistically
      significant at the end of the evaluation period. Bone resorption, measured as
      loss of total bone height in panoramic radiographs, was initially more pronounced
      following onlay augmentations (>20% after 12 months of observation). The degree
      of resorption decreased in the further course of the study. Lower resorption
      rates and a higher overall success rate were demonstrated for the sinus lift
      group.

PMID- 15978776
TI  - Bone quality at the implant site after reconstruction of a local defect of the
      maxillary anterior ridge with chin bone or deproteinised cancellous bovine bone.
AB  - The purpose of this study was to investigate the quality of bone at grafted
      implant sites in the anterior maxilla. Grafting of these sites was necessary
      because of insufficient bone volume in a buccopalatinal direction (width at the
      top of the crest 1-3mm). Reconstruction was performed with chin bone (N=5), chin
      bone and a resorbable Bio-Gide GBR membrane (N=5) or Bio-Oss spongiosa granules
      in combination with a Bio-Gide GBR membrane (N=5). Biopsies were taken prior to
      implantation, i.e. 3 months after grafting with chin bone, and 6 months after
      grafting with Bio-Oss. Evaluation was done by assessing the histological and
      histomorphometric characteristics of full-length biopsies taken from the actual
      implant site. Both areas with non-vital bone and areas with apposition of bone
      and remodelling phenomena were observed in the chin bone group at the time of
      placement of the implants. Similar results were observed at implant sites
      reconstructed with a chin bone graft covered by a membrane. In the chin bone
      group without and with a GBR membrane, the mean total bone volume (TBV) was
      55.2+/-6.8% and 57.7+/-11.5%, respectively; the marrow connective tissue volume
      (MCTV) was 44.8+/-6.8% and 42.3+/-11.5%, respectively. Remnants of the resorbable
      GBR membrane were not detected. In the Bio-Oss((R)) group, at implant placement
      some newly formed bone was observed in the connective tissue surrounding the Bio
      Oss((R)) particles (mean TBV (newly formed bone) 17.6+/-14.5%), but most
      particles were surrounded by connective tissue. No convincing signs of
      remodelling were observed (mean remaining Bio-Oss volume 40.5+/-9.3%; mean MCTV
      41.9+/-13.1%). No implants were lost during follow up (12 months). At the time of
      placement of the implants the grafting material (either chin bone or Bio-Oss is
      still not fully replaced by new vital bone. In case of Bio-Oss, most of the
      grafting material is even still present. Despite these differences, the 1-year
      clinical results were very good and comparable between the various grafting
      techniques applied.

PMID- 15978777
TI  - Autoimmune epilepsy: distinct subpopulations of epilepsy patients harbor serum
      autoantibodies to either glutamate/AMPA receptor GluR3, glutamate/NMDA receptor
      subunit NR2A or double-stranded DNA.
AB  - We studied 82 patients with different types of epilepsy and 49 neurologically
      intact non-epileptic controls, and identified three different subpopulations of
      epilepsy patients bearing significantly elevated levels of autoantibodies to
      either GluR3B-peptide of glutamate/AMPA receptor subtype 3 (17/82; 21% of
      patients), or to a peptide of NR2A subunit of glutamate/NMDA receptors (15/82;
      18%), or to double-stranded (ds) DNA, the hallmark of systemic lupus
      erythematosus (13/80; 16%). Most patients had only one antibody type, arguing
      against cross-reactivity. Nearly all anti-dsDNA Ab-positive patients did not
      harbor anti-nuclear autoantibodies. Most patients had no history of brain damage,
      febrile convulsions, early onset epilepsy, acute epilepsy or intractable
      seizures. We suggest to measure the 'autoimmune-fingerprints' of epilepsy
      patients for diagnostic and therapeutic purposes.

PMID- 15978778
TI  - Determining the chronology and components of psychosis onset: The Nottingham
      Onset Schedule (NOS).
AB  - The Nottingham Onset Schedule (NOS) is a short, guided interview and rating
      schedule to measure onset in psychosis. Onset is defined as the time between the
      first reported/observed change in mental state/behaviour to the development of
      psychotic symptoms. Onset is conceptualised as comprising of (i) a prodrome of
      two parts: a period of 'unease' followed by 'non-diagnostic' symptoms; (ii)
      appearance of psychotic symptoms; and (iii) a build-up of diagnostic symptoms
      leading to a definite diagnosis. Twenty consecutive cases of first-episode
      psychosis were administered the NOS schedule to determine its psychometric
      properties including inter-rater and test-retest reliability. Its clinical and
      research potential as a reliable measure of duration of untreated psychosis (DUP)
      was assessed in a cohort of 99 cases of first-episode psychosis (56
      schizophrenia, 43 affective psychoses). NOS identified all prodromal symptoms
      previously reported in other studies. There was high degree of inter-rater and
      test-retest reliability for all components of NOS. Duration of untreated
      psychosis was significantly longer (p<0.05) in schizophrenia (mean 179 days, S.D.
      344; median 52 days) than in affective psychosis (mean 15 days, S.D. 116; median
      12 days) but there were no gender differences between lengths of prodrome or
      treatment delays. The NOS provides a standardised and reliable way of recording
      early changes in psychosis and identifying relatively precise time points for
      measuring several durations in emerging psychosis. The scale is easy to use and
      is not time-consuming or labour intensive. Onset, as measured by NOS, is
      significantly longer in schizophrenic disorders than in affective psychosis. A
      small proportion of schizophrenia cases have very long DUP. Some cases with
      schizophrenia receive anti-psychotics in the prodromal phase, prior to the
      emergence of frank psychotic symptoms.

PMID- 15978779
TI  - Negative priming in schizophrenia revisited.
AB  - Reduced spatial negative priming (SNP) in schizophrenia is commonly attributed to
      the inability to filter out irrelevant information. However, some investigators
      have suggested that reduced SNP in patients is caused by either perceptual
      mismatching or salience of the distracter. The goal of the present study was to
      determine the influence of these perceptual processes. In this preliminary
      report, we present data of 15 schizophrenia patients on atypical medication and
      15 matched healthy controls. Compared to controls, patients showed a reduced SNP
      effect, even when controlled for perceptual mismatching. This reduced effect was
      not affected by distracter salience.

PMID- 15978780
TI  - Deficits in sustained attention in schizophrenia but not in bipolar disorder.
AB  - The aim of the present study was to investigate sustained attention in remitted
      patients with bipolar disorder and in patients with schizophrenia, as compared to
      each other and to healthy controls; a secondary aim was to investigate the
      correlations of different symptom dimensions with performance on sustained
      attention in the two patient groups. Participants were 29 (18 men) outpatients
      with schizophrenia (SZ), 19 (8 men) patients with bipolar disorder I (BP) in
      remission, and 30 (15 men) healthy controls (HC); all three groups were matched
      on age, sex ratio, and level of education. Symptom severity (positive symptoms,
      negative symptoms, and general psychopathology) of patients with SZ were assessed
      with the Greek version of the Positive and Negative Syndrome Scale (PANSS);
      residual affective symptoms of patients with BP were assessed with the Young
      Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale
      (MADRS). Sustained attention was measured by means of the Penn Continuous
      Performance Test (PCPT). The three groups differed significantly on the PCPT
      scores. Patients with SZ performed more poorly than both the BP and HC groups,
      whereas patients with BP did not differ significantly from HC. Performance on the
      PCPT did not correlate significantly with scores on the YMRS and MADRS in
      patients with BP. Also, scores on the PCPT did not correlate significantly with
      scores on any of the three subscales of the PANSS. Outpatients with schizophrenia
      presented deficits in sustained attention, whereas patients with bipolar disorder
      I in remission did not manifest such impairment. These results imply that
      impaired sustained attention might be a more enduring deficit in schizophrenia
      than it appears to be in bipolar disorder.

PMID- 15978781
TI  - The course of cognitive functioning in first episode psychosis: changes over time
      and impact on outcome.
AB  - This three year longitudinal study examined the cognitive performance of 247
      individuals who recently presented with a first episode of psychosis. Using a
      comprehensive battery of cognitive tests, we assessed cognition at baseline, 1
      year and 2-year follow-ups. Assessments also included positive and negative
      symptoms, depression, social outcome and substance use. There were several
      significant improvements in cognition over the two-year period which were usually
      matched by improvements in a matched non-psychiatric control group. Regression
      analyses demonstrated that after controlling for symptoms cognitive impairment
      accounted for 4-6% of the variance in social functioning. Our results suggest
      that impaired cognition exists in the very early stages of a psychotic illness
      and that there is no decline over time. Secondly, our results suggest that,
      although related, poor social functioning deficits may be independent of
      cognitive impairment. Finally there are implications for improved methodology in
      the assessment of both cognitive and social functioning.

PMID- 15978782
TI  - Tri-ethnic variations of co-morbid substance and alcohol use disorders in
      schizophrenia.
AB  - OBJECTIVES: This study examined the differential prevalence of substance and
      alcohol use disorders among European Americans, African Americans, and Latinos
      with schizophrenia (n = 6424) who received public mental health services in San
      Diego County during fiscal year 2002-2003. METHODS: Data were obtained from the
      public mental health database used by the San Diego County Mental Health System.
      Chi-Square analyses and stepwise logistic regression analyses were used to
      examine differences regarding the prevalence of substance and alcohol use among
      clients with schizophrenia and schizoaffective disorder, and to analyze the
      sociodemographic variables associated with this co-morbidity. RESULTS:
      Significant differences in the prevalence of diagnosed co-morbidity were found
      across the ethnic groups. Rates of co-morbid diagnosis among African Americans
      (25%) were significantly higher than those among European Americans (22%) and
      Latinos (19%). Logistic regression results revealed ethnicity was a significant
      predictor of co-morbid substance and alcohol use, as was being homeless and male.
      Among Latinos, language preference was also a significant predictor. Latinos who
      denoted English as their primary language were 1.7 times more likely to be
      diagnosed with co-morbid substance or alcohol use disorders than Latinos who
      denoted Spanish. CONCLUSIONS: Among people with schizophrenia, there were
      significant differences in prevalence rates and predictors of diagnosed co-morbid
      substance and alcohol use disorders. Future research is needed to examine the
      relationship among language preference, level of acculturation, and subsequent
      diagnosing barriers for Latinos. Among African Americans, the reasons behind
      increased co-morbidity rates need to be examined, and homelessness should be
      carefully addressed among all three ethnic groups.

PMID- 15978783
TI  - Treatment concepts of day hospitals for general psychiatric patients. Findings
      from a national survey in Germany.
AB  - Psychiatric day hospital treatment concepts have to deal with a wide spectrum of
      mental disorders. We raised the question, if day hospitals can be differentiated
      concerning their treatment concepts and if so how much this is reflected in their
      structural and procedural features. In 1999 a survey was initiated concerning
      structure, concept and method of treatment in psychiatric day hospitals for
      adults in Germany. Furthermore data concerning rate of utilization, patients'
      characteristics and aspects of referral and further treatment were ascertained.
      One hundred and seventy-three (63.4%) of 273-day hospitals contacted took part in
      the inquiry. The data were interpreted using multivariate as well as non
      parametric procedures. The results show that treatment concepts of day hospitals
      can be specified as three main areas of function (psychotherapy, crisis
      intervention orientated treatment alternative, rehabilitation) and four
      therapeutic orientations (psychodynamic social psychiatric, behavioral social
      psychiatric, psychodynamic, sociotherapeutic). Structural features are
      predominantly comparable and the differences found concerning the treatment
      concepts are especially related to patients' characteristics and some procedural
      features. The conclusion is that the differentiation of day hospital treatment
      concepts should be taken into consideration in planning psychosocial treatment
      services as well as in day hospital evaluation research.

PMID- 15978784
TI  - Reduced glucose metabolism in temporo-parietal cortices of women with borderline
      personality disorder.
AB  - Individuals with borderline personality disorder (BPD) and posttraumatic stress
      disorder (PTSD) often experience dissociative symptoms. Evidence is increasing
      that stress-related hyperglutamatergic states may contribute to dissociative
      symptoms and neurodegeneration in temporo-parietal cortical areas. Seventeen
      young women with BPD who had been exposed to severe childhood physical/sexual
      abuse and presented with pronounced dissociative symptoms underwent (18)fluoro-2
      deoxyglucose positron emission tomography (FDG-PET). Nine healthy, matched
      volunteers served as comparison subjects. Borderline subjects displayed reduced
      FDG uptake (as analyzed by SPM) in the right temporal pole/anterior fusiform
      gyrus and in the left precuneus and posterior cingulate cortex. Impaired memory
      performance among borderline subjects was significantly correlated with metabolic
      activity in ventromedial and lateral temporal cortices. Our results demonstrate
      regional hypometabolism in temporal and medial parietal cortical regions known to
      be involved in episodic memory consolidation and retrieval. Currently, the
      precuneus/posterior cingulate cortex is modeled as part of a network of tonically
      active brain regions that continuously gather information about the world around
      and within us. Decreased resting metabolic rate of these regions may reflect
      dissociative symptoms and possibly also identity disturbances and interpersonal
      difficulties of individuals with BPD.

PMID- 15978785
TI  - Adsorption of fibrinogen on tantalum oxide, titanium oxide and gold studied by
      the QCM-D technique.
AB  - The adsorption of human fibrinogen on tantalum oxide, titanium oxide and gold
      surfaces has been studied by quartz crystal microbalance with dissipation (QCM-D)
      at 37 degrees C. Two different protein concentrations have been used, one close
      to physiological concentration (1 mg/ml) and one significantly lower (0.033
      mg/ml). To further characterize the adsorbed fibrinogen layer, the subsequent
      binding of both polyclonal and monoclonal antibodies of fibrinogen is studied. We
      found that the viscoelastic properties of the fibrinogen layer depends strongly
      on the initial protein concentration. The trend is generally seen for all three
      surfaces. The fibrinogen layer on gold and tantalum oxide is found to have the
      same viscoelastic properties, which are different from those found for the
      fibrinogen layer adsorbed on titanium oxide. The dependency of the surface
      chemistry on the viscoelastic properties of the fibrinogen layer is observed
      directly for the 0.033 mg/ml solution, and indirectly through the antibody
      response for the 1 mg/ml solution. From this we conclude that the orientation
      and/or denaturation of fibrinogen on a surface depends on the surface chemistry
      and the protein concentration in the solution, and that the binding of antibodies
      is a useful way to detect this difference.

PMID- 15978786
TI  - In vitro haemocompatibility and stability of two types of heparin-immobilized
      silicon surfaces.
AB  - Heparin was covalently immobilized onto a silicon surface by two different
      methods, carbodiimide-based immobilization and photo-immobilization. In the
      former method, a (3-aminopropyl) trimethoxysilane (APTMS) self-assembled
      monolayer (SAM) or multilayer was first coated onto the silicon surface as the
      bridging layer, and heparin was then attached to the surface in the presence of
      water-soluble carbodiimide. In the latter method, an octadecyltrichlorosilane
      (OTS) SAM was coated on the silicon surface as the bridging layer, and heparin
      was modified by attaching photosensitive aryl azide groups. Upon UV illumination,
      the modified heparin was then covalently immobilized onto the surface. The
      hydrophilicity of the silicon surface changed after each coating step, and
      heparin aggregates on APTMS SAM and OTS SAM were observed by atomic force
      microscopy (AFM). In vitro haemocompatibility assays demonstrated that the
      deposition of APTMS SAM, APTMS multilayer and OTS SAM enhanced the silicon's
      haemocompatibility, which was further enhanced by the heparin immobilization.
      There is no evident distinction regarding the haemocompatibility between the
      heparin-immobilized surfaces by both methods. However, heparin on silicon with
      APTMS SAM and multilayer as the bridging layers is very unstable when tested in
      vitro with a saline solution at 37 degrees C, due to the instability of APTMS SAM
      and multilayer on silicon. Meanwhile, photo-immobilized heparin on silicon with
      OTS SAM as the bridging layer showed superb stability.

PMID- 15978787
TI  - Equilibrium of the reaction between dissolved sodium sulfide and biologically
      produced sulfur.
AB  - The equilibrium of the heterogeneous reaction between dissolved sodium sulfide
      and biologically produced sulfur particles has been studied. Biologically
      produced sulfur was obtained from a bioreactor of a hydrogen sulfide removal
      process in which the dominating organism is Thiobacillus sp. W5. Detailed
      knowledge of this reaction is essential to understand its effect on the process.
      The results were compared with the equilibrium of the reaction of sulfide with
      'inorganic' elemental sulfur. The equilibrium between dissolved sodium sulfide
      and biologically produced sulfur particles can be described by an equilibrium
      constant, K(x), which consists of a weighted sum of constants for polysulfide
      ions of different chain length, rather than a true single equilibrium constant.
      For biologically produced sulfur pK(x)=9.10+/-0.08 (21 degrees C) and 9.17+/-0.09
      (35 degrees C) with an average polysulfide chain length x=4.91+/-0.32 (21 degrees
      C) and 4.59+/-0.31 (35 degrees C). The pK(x) value for biologically produced
      sulfur is significantly higher than for reaction of dissolved sodium sulfide with
      inorganic sulfur (pK(x)=8.82; 21 degrees C). This difference is probably caused
      by the negatively charged polymeric organic layer, which is present on
      biologically produced sulfur but absent with "inorganic" sulfur. Specific binding
      of polysulfide ions to the organic layer results in a higher polysulfide
      concentration at the reaction site compared to the bulk concentration. This
      results in an apparent decrease of the measured equilibrium constant, K(x).

PMID- 15978788
TI  - Effects of vascular endothelial growth factor (VEGF) and chondroitin sulfate A on
      human monocytic THP-1 cell migration.
AB  - Angiogenesis serves as a crucial factor in disease development and progression,
      such as cancer metastasis, and monocyte migration is one of the key steps for
      angiogenesis. Therapeutic modulation of angiogenesis is a promising new
      therapeutic avenue under investigation. In this study, effects of vascular
      endothelial growth factor (VEGF) and chondroitin sulfate A on monocyte migration
      were investigated. Human monocytic THP-1 cells were from Riken Cell Bank
      (Tsukuba, Japan) and vascular endothelial cells (VECs) were obtained from swine
      thoracic aorta. The migration experimental system was adapted from Falcontrade
      mark Cell Culture Inserts with pore sizes of 3 and 8 microm cultured endothelial
      cells or not on the insert polyethylene terephthalate (PET) membranes. Four VEGF
      concentrations (0, 10, 50 and 100 ng/ml) and three concentrations of chondroitin
      sulfate A (0, 1.25 and 5.0 mg/ml) were used to investigate their effects on THP-1
      cell migration ability through PET membranes and VECs monolayer. The THP-1 cell
      migration was evaluated by counting the number of migrated cells related to the
      total number of cells under a microscope. We counted the migration cells every 1
      h on a Tatai-type hemocytometer using an inverted microscope for total 7 h. For
      inserts with pore sizes of 3 and 8 microm, the THP-1 cell migration increased
      with VEGF concentrations; however, cell migration decreased with the chondroitin
      sulfate A concentration. Our results demonstrated that VEGF accelerated monocyte
      migration through endothelial monolayer and chondroitin sulfate A is an effective
      inhibitor of monocyte migration for angiogenesis.

PMID- 15978789
TI  - A water-soluble prodrug of cyclosporine A for ocular application: a stability
      study.
AB  - UNIL088 is a water-soluble prodrug of cyclosporine A (CsA) developed for topical
      eye delivery. Such a prodrug has to fulfil two paradoxical requirements as it
      must be rapidly hydrolysed under physiological conditions but also retain a long
      shelf-life in aqueous media. This study has been conducted to explore the
      stability of UNIL088 formulated as an eyedrop solution. The stability study of
      the prodrug was performed over a pH range of 5-7 at 20 degrees C and at various
      ionic strengths. The molecule was more stable at pH 5 than at pH 7 with
      conversion rate constant of 3.2 x 10(-3) and 26.0 x 10(-3)days(-1), respectively.
      The effect of temperature was studied at four different temperatures and
      activation energy was determined. Conversion of UNIL088 followed a pseudo-first
      order kinetic with an activation energy of 79.4 kJ mol(-1). Due to its low
      solubility, CsA generated precipitated in the solution. The average size of CsA
      precipitates, determined by photon spectroscopy, was 0.22 and 1.08 microm at 7
      and 14 days, respectively. The hydrolysis mechanism was partially elucidated by
      identification of the intermediate pSer-Sar-CsA.

PMID- 15978790
TI  - [Rehospitalization of very preterm infants in the first year of life. Comparison
      of 2 groups: 1997 and 2002].
AB  - OBJECTIVE: The aim of the study was to compare the rehospitalization rate in the
      first year of life between 2 groups of very preterm infants born on 1997 and
      2002; then we compared the very preterm infants' rehospitalization rate between
      our retrospective 1997 group and literature (including French cohort Epipage).
      PATIENTS AND METHODS: Our retrospective study included all neonates born<or=33
      GA, living in Gironde, discharged from neonatal unit at children's hospital of
      Bordeaux on 1997 and 2002 and rehospitalized during their first year of life.
      RESULTS: Respectively 29.1% and 30.1% premature infants were rehospitalized (at
      least once) in 1997 and 2002 (38.2% in Epipage cohort, no statistical
      difference). Mean number of rehospitalizations was 1.66 in 1997 and 1.77 in 2002.
      Mean duration of rehospitalization was 11.8 days in 1997 and 16.8 days in 2002.
      These data showed no statistical difference between 1997 and 2002. Respiratory
      disease was the first reason of rehospitalization. Several factors were
      correlated with an increase risk of rehospitalization: birth weight less than
      1000 g, chronic lung disease and gestational age less than 28 weeks at birth
      (only in 2002 cohort). CONCLUSION: Rehospitalization rate remained stable between
      1997 and 2002 whereas during this period of time, the gravity of these preterm
      infants had increased. The use of specific hospital discharge procedure
      represents a real benefit for premature infants. It must be continued after the
      discharge with the establishment of a strong network with the implication of
      parents, infants, hospital and city health workers. It may contribute to limit
      the very premature babies' rehospitalization rate.

PMID- 15978791
TI  - The role of aspirin-triggered lipoxins in the mechanism of action of aspirin.
AB  - Few drugs have treated so many diseases, provided us with so much understanding
      of their pathogenesis, and tested our scientific creativity over the last 100
      years as much as aspirin. Originally, the beneficial effects of aspirin were
      shown to stem from its inhibition of cyclooxygenase (COX 2)-derived prostanoids,
      fatty acid metabolites that modulate host defense and regulate the cardiovascular
      system. However, the inhibition of COX 2 enzyme activity and prostaglandin
      synthesis has never fully explained aspirin's repertoire of anti-inflammatory
      effects, leaving many questions pertaining to its true mechanism of action
      unanswered. Here, data from a series of comparatively recent experiments
      exploring aspirin's unique ability to acetylate the active site of inducible COX
      2 and generate a family of lipid mediators called the epi-Lipoxins will be
      discussed in light of their ability to exert profound modulatory effects on the
      innate and adaptive immune systems.

PMID- 15978792
TI  - Taking insult from injury: lipoxins and lipoxin receptor agonists and
      phagocytosis of apoptotic cells.
AB  - Phagocytic clearance of apoptotic cells plays a pivotal role in the resolution of
      inflammation. Recent evidence has shown that such processes can be regulated by
      endogenous mediators, suggesting that specific mimetics may have therapeutic
      potential in chronic inflammation and autoimmune disorders. Here we review the
      mechanisms underlying recognition and engulfment of apoptotic cells and
      regulation of these processes by lipoxins and lipoxin receptor agonists.

PMID- 15978793
TI  - The control of peroxisome number and size during division and proliferation.
AB  - Like other subcellular organelles, peroxisomes divide and segregate to daughter
      cells during cell division, but this organelle can also proliferate or be
      degraded in response to environmental cues. Although the mechanisms and genes
      involved in these processes are still under active investigation, an important
      player in peroxisome proliferation is a dynamin-related protein (DRP) that is
      recruited to the organelle membrane by a DRP receptor. Related DRPs also function
      in the division of mitochondria and chloroplasts. Many other proteins and signals
      regulate peroxisome division and proliferation, but their modes of action are
      still being studied.

PMID- 15978794
TI  - Autophagosomes: biogenesis from scratch?
AB  - To survive extreme environmental conditions, and in response to certain
      developmental and pathological situations, eukaryotic organisms employ the
      catabolic process of autophagy. This degradative pathway allows cells to
      eliminate large portions of the cytoplasm, from aberrant protein aggregates to
      superfluous or damaged organelles and even entire organisms such as invading
      bacteria. Structures targeted for destruction are sequestered into large double
      membrane vesicles called autophagosomes and then delivered into the interior of
      the lysosome or vacuole, where they are consumed by resident hydrolases.
      Autophagosome formation during selective autophagy is dependent upon the cargoes,
      and in all cases seems to involve expansion of the sequestering membrane.

PMID- 15978795
TI  - The elusive sizer.
AB  - Size control has been a topic of interest to cell biologists for over a century,
      but insights into cell size control mechanisms have until recently been
      relatively sparse. Determining whether cells have a size measurement mechanism
      and how it might operate has proven difficult. The nucleocytoplasmic ratio is one
      of the few conserved features of size control but little is know about how it is
      measured. Models where growth and division can be uncoupled have been
      underexploited, but have considerable potential for gaining insights into the
      contribution of the nucleocytoplasmic ratio to cell size regulation.

PMID- 15978796
TI  - Aerobic composting of waste activated sludge: kinetic analysis for
      microbiological reaction and oxygen consumption.
AB  - In order to examine the optimal design and operating parameters, kinetics for
      microbiological reaction and oxygen consumption in composting of waste activated
      sludge were quantitatively examined. A series of experiments was conducted to
      discuss the optimal operating parameters for aerobic composting of waste
      activated sludge obtained from Kawagoe City Wastewater Treatment Plant (Saitama,
      Japan) using 4 and 20 L laboratory scale bioreactors. Aeration rate, compositions
      of compost mixture and height of compost pile were investigated as main design
      and operating parameters. The optimal aerobic composting of waste activated
      sludge was found at the aeration rate of 2.0 L/min/kg (initial composting mixture
      dry weight). A compost pile up to 0.5 m could be operated effectively. A simple
      model for composting of waste activated sludge in a composting reactor was
      developed by assuming that a solid phase of compost mixture is well mixed and the
      kinetics for microbiological reaction is represented by a Monod-type equation.
      The model predictions could fit the experimental data for decomposition of waste
      activated sludge with an average deviation of 2.14%. Oxygen consumption during
      composting was also examined using a simplified model in which the oxygen
      consumption was represented by a Monod-type equation and the axial distribution
      of oxygen concentration in the composting pile was described by a plug-flow
      model. The predictions could satisfactorily simulate the experiment results for
      the average maximum oxygen consumption rate during aerobic composting with an
      average deviation of 7.4%.

PMID- 15978797
TI  - Management of healthcare wastes.

PMID- 15978798
TI  - Catechol sensor using poly(aniline-co-o-aminophenol) as an electron transfer
      mediator.
AB  - In this work, poly(aniline-co-o-aminophenol) (copolymer) was used as an electron
      transfer mediator in the electrochemical oxidation of catechol due to its
      reversible redox over a wide range of pH. The experimental results indicate that
      the anodic peak potential of catechol at the copolymer electrode is lower than
      that at the platinum electrode in a solution consisting of catechol and sodium
      sulfate with pH 5.0, and the activation energy for the electrochemical oxidation
      of catechol at the copolymer electrode is low (23.6 kJ mol(-1)). These are strong
      evidence for the electrocatalytic oxidation of catechol at the copolymer
      electrode. The -OH group on the copolymer chain plays an important role in the
      electron transfer between the copolymer electrode and catechol in the solution.
      Based on the catalytic oxidation, the copolymer is used as a sensor to determine
      the concentration of catechol. The response current of the sensor depends on the
      concentration of catechol, pH, applied potential and temperature. At 0.55 V
      (versus saturated calomel reference electrode (SCE)) and pH 5.0, the sensor has a
      fast response (about 10s) to catechol and good operational stability. The sensor
      shows a linear response range between 5 and 80 microM catechol with a correlation
      coefficient of 0.997. It was found that phenol and resorcinol cannot be oxidized
      at the copolymer electrode at potentials < or =0.55 V, so controlling the sensor
      potential affords a good way of avoiding the effect of phenol and resorcinol on
      the determination of catechol.

PMID- 15978799
TI  - Fiber-optic biosensor to assess circulating phagocyte activity by
      chemiluminescence.
AB  - We describe herein the construction of a novel computerized multi-sample
      temperature-controlled luminometer for a fiber array-based biosensor to monitor
      circulating phagocyte activity. It can perform simultaneously integral
      measurements of chemiluminescence emitted from up to six samples containing less
      than 0.5 microl whole blood while the samples and detector do not change their
      position during the measurement cycle. The optical fibers in this luminometer are
      used as both light guides and solid phase sample holders. The latter feature of
      the instrument design simplifies the assessment process of both the extra
      cellular and the intra-cellular parts of the phagocyte-emitted chemiluminescence
      using the same system. We describe some examples or proof of principle for the
      use of the biosensor. This new technology may find use in a wide range of
      analytical luminescence applications in biology, biophysics, biochemistry,
      toxicology and clinical medicine.

PMID- 15978800
TI  - The frequency and pattern of cardiotoxicity observed with capecitabine used in
      conjunction with oxaliplatin in patients treated for advanced colorectal cancer
      (CRC).
AB  - We examined the cardiotoxicity in 153 patients treated with capecitabine and
      oxaliplatin in two prospective trials for advanced colorectal cancer. Ten
      patients (6.5%) developed cardiac events. One patient (0.7%) had sudden death,
      one patient developed cardiac failure with raised troponin I while another
      developed ventricular tachycardia (VT). The remaining seven patients (4.6%)
      experienced angina and three of the seven patients had raised troponin I, one of
      which developed ventricular fibrillation. Eight events occurred within cycle 1
      (median cycle 1 day 10). Four patients with angina and one patient with VT
      recovered on stopping capecitabine, four patients required additional medical
      management and the remaining patient died suddenly at home. Patients with
      ischaemic heart disease appeared to be at increased risk. Physicians and patients
      need to be aware of these complications, so that prompt discontinuation of
      treatment and appropriate interventions may be instituted.

PMID- 15978801
TI  - Hereditary breast cancer growth rates and its impact on screening policy.
AB  - Imaging is often performed yearly for the surveillance of BRCA1/2 mutation
      carriers and women at high familial breast cancer risk. Growth of cancers in
      carriers may be faster as these tumours are predominantly high grade.
      Quantitative data on tumour growth rates in these 2 groups are lacking. Here, we
      have examined 80 high-risk women under surveillance for tumour size at diagnosis
      and preceding examinations at mammography and/or MRI. Tumour volume doubling time
      (DT) was assessed in 30 cancers in BRCA1/2 mutation carriers and 25 non-carriers.
      Impact of age and menopausal status were also evaluated. Mean DT of all invasive
      cancers was shorter in carriers (45 days CI: 26-73) than non-carriers (84 days
      CI: 58-131) (P = 0.048). Mean age at diagnosis was lower in carriers (40 years)
      than non-carriers (45 years) (P = 0.007). At multivariable analysis only age (P =
      0.03), not risk-group (P = 0.26) nor menopause (P = 0.58) correlated
      significantly with DT. The mean growth rate slowed down to half in each
      successive 10 years-older group. In conclusion, age at detection indicated the
      growth rates of hereditary and familial breast cancers. It is recommended that
      the screening frequency should be adjusted according to a woman's age and a high
      sensitive biannual test may be appropriate before the age of 40 years.

PMID- 15978802
TI  - Confirmation of response in cancer clinical trials: a meaningless exercise?

PMID- 15978803
TI  - Removal of basic dyes from aqueous medium using a novel polymer: Jalshakti.
AB  - Studies were carried out to remove basic dyes such as safranine T, methylene
      blue, crystal violet, light green, brilliant milling violet and patent blue VS
      from their aqueous solutions using biodegradable polymeric absorbent material,
      viz., Jalshakti (JS). Results showed that 93% safranine T, 98% methylene blue and
      84% crystal violet were adsorbed on JS relative to their initial concentration
      (10 mg L(-1)). The optimum pH was found to be 6.0+/-0.5 and smaller size of
      particle of JS resulted better adsorptive removal of the dyes. IR spectroscopic
      and potassium ion release studies revealed that basic dyes were selectively
      removed through adsorption-ion-exchange mechanism involving carboxylic groups and
      K+ ions of JS.

PMID- 15978804
TI  - Predictive models for hERG potassium channel blockers.
AB  - We report here a general method for the prediction of hERG potassium channel
      blockers using computational models generated from correlation analyses of a
      large dataset and pharmacophore-based GRIND descriptors. These 3D-QSAR models are
      compared favorably with other traditional and chemometric based HQSAR methods.

PMID- 15978805
TI  - Neuroprotective effects of naturally occurring biflavonoids.
AB  - We examined neuroprotective effects of naturally occurring biflavonoids on
      oxidative stress-induced and amyloid beta peptide-induced cell death in neuronal
      cells. Among the nine biflavonoids tested, amentoflavone, ginkgetin, and
      isoginkgetin exhibited strong neuroprotection against cytotoxic insults induced
      by oxidative stress and amyloid beta, suggesting their therapeutic potential
      against neurodegenerative diseases, including ischemic stroke and Alzheimer's
      disease.

PMID- 15978806
TI  - 2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs: highly
      potent, orally active, adenosine A2A antagonists. Part 1.
AB  - The structure-activity relationship of this novel class of compounds based on 2
      (2-furanyl)-7-phenyl[1,2,4]-triazolo[1,5-c]pyrimidin-5-amine, 1, and its analogs
      was evaluated for their in vitro and in vivo adenosine A(2A) receptor antagonism.
      Several compounds displayed oral activity at 3 mg/kg in a rat catalepsy model.
      Specifically, compound 8g displayed an excellent in vitro profile, as well as a
      highly promising in vivo profile.

PMID- 15978807
TI  - SAR studies of 6-aryl-1,3-dihydrobenzimidazol-2-ones as progesterone receptor
      antagonists.
AB  - We have previously reported that the aryl substituted benzimidazolones,
      benzoxazinones, and oxindoles (e.g., 1-3) are progesterone receptor (PR)
      antagonists and have recently disclosed that the nature of 5- and 6-aryl moieties
      played a critical role in PR functional activity in the oxindole and
      benzoxazinone templates. For example, replacing the phenyl group of PR
      antagonists 2 and 3 with a 5'-cyanopyrrol-2'-yl moiety switched their functional
      activity to PR agonist activity (2a and 3a). These findings prompted us to
      examine if there is a similar effect of the 6-aryl moieties on the PR functional
      activity for the benzimidazolone template. Numerous analogs, such as 5, showed
      potent PR antagonist activity with about a 10-fold increase in potency as
      compared to those reported earlier in the same series. More interestingly,
      pyrrole-containing benzimidazolones 24-27 remained as PR antagonists in contrast
      to the PR agonist activity switch for oxindole and benzoxazinone scaffolds when a
      5'-cyanopyrrol-2'-yl group was installed as a pendant aryl group.

PMID- 15978808
TI  - Synthesis of some diguanidino 1-methyl-2,5-diaryl-1H-pyrroles as antifungal
      agents.
AB  - A series of novel 2,5-bis(guanidino-aryl)-1-methyl-1H-pyrroles 9a-h has been
      synthesized starting from 1-methyl-1H-pyrrole. The antifungal activities of
      compounds were evaluated by in vitro agar diffusion and broth dilution assay
      against Candida spp. and Aspergillus spp. Compound 9c from this series was found
      to be equipotent or more potent than fluconazole, whereas compound 9d was
      comparable to fluconazole against most of the tested strains.

PMID- 15978809
TI  - Total synthesis and antiangiogenic activity of cyclopentane analogues of
      fumagillol.
AB  - Novel cyclopentane analogues of fumagillol were synthesized and their endothelial
      cell proliferation inhibitory activities were evaluated. The cyclopentane
      fumagillol derivatives were synthesized from (-)-2,3-O-isopropylidene-D
      erythronolactone via stereoselective glycolate Claisen rearrangement and
      intramolecular ester enolate alkylation as key steps.

PMID- 15978810
TI  - Anti-HIV properties of cationic fullerene derivatives.
AB  - A series of regioisomeric bis-fulleropyrrolidines bearing two ammonium groups
      have been synthesized and their activities against HIV-1 and HIV-2 have been
      evaluated. Two trans isomers have been endowed with interesting antiviral
      properties, confirming the importance of the relative positions of the
      substituent on the C(60) cage. In addition, reduced amphiphilicity of molecules
      to other compounds previously reported decreases their cytotoxicity in CEM cell
      cultures. None of the compounds showed any inhibitory activity against a variety
      of DNA and RNA viruses other than HIV.

PMID- 15978811
TI  - Discovery and SAR of biaryl piperidine MCH1 receptor antagonists through solid
      phase encoded combinatorial synthesis.
AB  - An encoded combinatorial library based on aryl and biaryl piperidine scaffolds
      was designed and synthesized. Screening of this library resulted in the discovery
      of high-nanomolar biaryl piperidine-based MCH1 receptor antagonists. Follow-up
      optimization using a parallel synthesis provided potent, single digit nanomolar
      antagonists.

PMID- 15978812
TI  - Experimental protocol for the kinematic analysis of the hand: definition and
      repeatability.
AB  - A quantitative and objective method based on the optoelectronic kinematic
      analysis of hand segments and on the calculation of global and partial
      parameters, which provide measures of the degree of long finger and thumb
      extension is proposed for the evaluation of the hand's voluntary range of motion
      and maximal opening of the fingers and thumb. To test the precision and
      repeatability of the method, the protocol was applied on 14 healthy subjects (28
      hands). The proposed parameters are repeatable and show a precision between 5.5
      degrees and 10.4 degrees (mean value: 7.3 degrees), comparable to values obtained
      with other methods. Advantages of the present approach include simultaneous
      analysis of all fingers, absence of cumbersome connecting cables and no need for
      individually customized devices. The method, also applied to the paretic hands of
      two hemiplegic stroke patients before and after electrical stimulation of the
      wrist and finger extensor muscles, has shown encouraging results for its clinical
      feasibility and utility in addition to functional tests.

PMID- 15978813
TI  - Regression analysis of gait parameters with speed in normal children walking at
      self-selected speeds.
AB  - Dimensionless analysis ensures that differences in sizes (e.g. height and weight)
      of children have a minimal influence on gait parameters. The results of changes
      in speed on gait parameters were examined using dimensionless analysis on data
      from a prospective 5-year study of 16 children. Linear regression analysis of
      peak and trough values of temporal distance parameters, ground reaction forces,
      joint angles, moments and powers provide a quantitative description of gait
      development with normalised speed. These linear relationships can be used to
      estimate gait parameters from speed measurements for normal subjects. However,
      caution is advised in using the data to attempt to predict an individual's gait
      parameters due to the wide spread of data about the regression lines and we do
      not recommend that the data be used to extrapolate the regression data to wider
      speed ranges.

PMID- 15978814
TI  - Migraine and risk of subarachnoid haemorrhage: a population-based case-control
      study.
AB  - OBJECTIVE: Evidence exists for an association between migraine and ischaemic
      stroke, but there is uncertainty about whether migraine is a risk factor for
      subarachnoid haemorrhage (SAH). METHODS: A multi-centre, population-based, case
      control study using cases of first-ever SAH during 1995-98 and matched controls
      in four study centres in Australia and New Zealand. Self- or proxy-reported
      history, frequency and characteristics of headaches, classified according to 1988
      International Headache Society diagnostic criteria. RESULTS: 206 of 432 (48%)
      cases and 236 of 473 (50%) controls had a history of headaches. The frequency and
      characteristics of headaches were similar between the two groups. No association
      was found in logistic regression analyses for history or frequency of headaches,
      or migraine headaches. CONCLUSIONS: No evidence was found for an association
      between recurrent headaches and SAH. Such information is important for
      counselling patients and families about the significance of past and ongoing
      headaches in relation to this illness.

PMID- 15978815
TI  - Design and synthesis of low molecular weight compounds with complement inhibition
      activity.
AB  - An attempt was made to synthesize a series of non-cytotoxic low molecular weight
      compounds of varying substitutions and functionalities having pharmacophore
      activity like carbonyl compounds, carboxylic acid and bioisosteres like tetrazole
      and phenyl acrylic acid. The in vitro assay of these analogues for the inhibition
      of complement activity revealed significant inhibitory activity for varying
      substituents and, particularly, for bioisosteres, that is, tetrazole and phenyl
      acrylic acid derivatives.

PMID- 15978816
TI  - Geldanamycin derivative inhibition of HGF/SF-mediated Met tyrosine kinase
      receptor-dependent urokinase-plasminogen activation.
AB  - Ansamycins, including geldanamycin and the derivative 17-allylamino-17
      demethoxygeldanamycin, and radicicol are known for their ability to tightly bind
      to the ATP-binding site of the amino-terminal domain region of heat shock protein
      90. We have found that geldanamycin and some of its derivatives can inhibit
      hepatocyte growth factor/scatter factor-mediated Met tyrosine kinase receptor
      dependent urokinase-plasminogen activation at femtomolar levels. Assessment is
      made of structural requirements for such an activity and evidence is given that
      distinguishes the target of such an activity from that of heat shock protein 90.

PMID- 15978817
TI  - Increasing the capability of MNBRP for the detection of anti-personnel landmines.
AB  - Monte Carlo simulations were used to show that even very small explosives (<100g)
      can be detected by monoenergetic neutron backscattering with resonance
      penetration (MNBRP) at a depth well beyond 30 cm when time slicing is used for
      background suppression. At the present state of technology no other nuclear
      method appears to have a comparable sensitivity or penetration capability. This
      method has been successfully tested experimentally at a depth of 16.5 cm. A
      substantial simplification of the detection procedure could be achieved either by
      taking advantage of the time shadow rather than the geometric shadow or by
      applying neutron threshold detectors. Using a threshold detector could simplify
      the application, too.

PMID- 15978818
TI  - The role of science in treaty verification.
AB  - Technologically advanced nations are currently applying more science to treaty
      verification than ever before. Satellites gather a multitude of information
      relating to proliferation concerns using thermal imaging analysis, nuclear
      radiation measurements, and optical and radio frequency signals detection. Ground
      stations gather complementary signals such as seismic events and radioactive
      emissions. Export controls in many countries attempt to intercept materials and
      technical means that could be used for nuclear proliferation. Nevertheless, we
      have witnessed a plethora of nuclear proliferation episodes, that were undetected
      (or were belatedly detected) by these technologies--the Indian nuclear tests in
      1998, the Libyan nuclear buildup, the Iranian enrichment program and the North
      Korea nuclear weapons program are some prime examples. In this talk, we will
      discuss some of the technologies used for proliferation detection. In particular,
      we will note some of the issues relating to nuclear materials control agreements
      that epitomize political difficulties as they impact the implementation of
      science and technology.

PMID- 15978819
TI  - Effect of the opaque and floury mutations on the accumulation of dry matter and
      protein fractions in maize endosperm.
AB  - Grains of nine opaque (o) and floury (fl) mutants of maize (Oh43o1, Oh43o2,
      B79o5, B37o7, W22o10, W22o11, W22o13, Oh43fl1 and Oh43fl2) were examined for the
      weight proportions of their component tissues and the content of eight nitrogen
      fractions in their endosperms. A linear regression was found connecting the
      amounts (mg per endosperm) of zeins and true proteins (crude proteins minus non
      protein nitrogen) for the non-opaque2 mutants. The data points connecting zeins
      to true proteins present in the mature endosperms of six wild-type (+) inbred
      lines and their o2 versions were located outside (+) or within (o2) the 95%
      confidence range of the regression line. The data obtained from the developing
      and mature endosperms of the W22o7 inbred line (Di Fonzo et al., Plant Sci.
      Lett., 1979, 77) and the floury portion of mature endosperms of three other wild
      type inbred lines fell practically on the regression line. The effects of
      genotype and environmental factors upon the relative accumulation rate of zeins
      were assessed from the present results and the data taken from the literature
      concerning the quantitative interdependence between zeins and true proteins in
      immature and mature endosperms.

PMID- 15978820
TI  - A giant osteoma of the mandible: case report.
AB  - A 53-year-old patient with a giant osteoma of the right mandible is presented.
      The clinicopathological features of osteoma of the mandible are discussed and
      Gardner's syndrome was excluded.

PMID- 15978821
TI  - Spheno-orbital meningiomas: interdisciplinary surgical approach, resectability
      and long-term results.
AB  - OBJECTIVE: To describe the interdisciplinary surgical approach in spheno-orbital
      meningiomas and to evaluate the operative results regarding resectability and
      functional outcome. PATIENTS AND METHODS: A series of 16 patients underwent
      surgical resection of spheno-orbital meningiomas followed by bony reconstruction.
      Four patients presented with a recurrent meningioma and had undergone surgical
      resection previously. Radical tumour removal was attempted in all cases, although
      no aggressive effort was made to remove tumour tissue infiltrating the cavernous
      sinus or soft tissues deep in the orbit to avoid severe functional disturbances.
      All patients but one were female (mean age 53 years). Mean follow-up period was
      68 months (range 4-155 months). RESULTS: The leading symptom was proptosis in 14
      patients, accompanied in 7 cases by progressive visual impairment. Surgical
      resection was thought to have been complete in 11 patients (69%) and incomplete
      in 5 (31%). Residual tumour was deliberately left when there was infiltration of
      the cavernous sinus (n = 4), the pterygopalatine fossa (n = 2) and/or the deep
      intraorbital soft tissues (n = 1). Tumour recurrence was observed in 9 patients,
      among whom were 6 patients with an initially "completely" resected meningioma.
      Eight patients underwent re-operation. Complete resection was achieved in 3 of
      these latter patients with an isolated exclusively intraorbital tumour
      manifestation. CONCLUSION: By means of combined skull base approaches, spheno
      orbital meningiomas are grossly resected totally with a long-term survival free
      of recurrence and an acceptable quality of life. In some cases, deliberate
      subtotal tumour resection is useful to avoid severe neurological damage with
      sufficient tumour control and a valuable progression-free survival.

PMID- 15978822
TI  - An audit of mandibular fractures treated by intermaxillary fixation using
      intraoral cortical bone screws.
AB  - INTRODUCTION: During the last 10 years, intermaxillary fixation using intraoral
      cortical bone screws has been introduced for the treatment of mandibular
      fractures. The aim of this work was to evaluate the indications and possible
      complications of this method. MATERIALS AND METHODS: Sixty-two patients with
      mandibular fractures, treated by intermaxillary fixation using these screws, were
      evaluated by preoperative and postoperative panoramic radiographs. Clinical
      testing was carried out for vitality and abnormal mobility of teeth adjacent to
      the site of screw insertions. To evaluate the efficacy of this method, different
      factors were considered such as possible iatrogenic dental injuries, loss,
      breakage or screw cover by oral mucosa and postoperative occlusion. RESULTS: The
      most important complication was iatrogenic damage to dental roots (1.5%), 4.9% of
      the screws were covered by oral mucosa and 1.9% were lost, while none were
      broken. Malocclusion was observed in one patient (1.6%) and lack of consolidation
      of a displaced fracture of the mandibular body in another patient. CONCLUSIONS:
      Use of intraoral cortical bone screws for intermaxillary fixation is a valid
      alternative to arch bars in the treatment of mandibular fractures. Iatrogenic
      injury to dental roots is the most important problem of this procedure, but can
      be minimized by an experienced surgeon.

PMID- 15978823
TI  - Distraction osteogenesis in the irradiated mandible. A case report.
AB  - BACKGROUND: Distraction osteogenesis has been suggested as a relatively simple
      method of mandibular reconstruction following ablative head and neck surgery.
      Some authors report good results in irradiated patients while other authors
      report limitations with this group of patients. PATIENT: In a 72-year-old male an
      attempt was made to reconstruct the irradiated mandible using distraction
      osteogenesis. RESULTS: Distraction osteogenesis only resulted in an enlarged soft
      tissue envelope, while there was no evidence of bone formation in the distraction
      gap. CONCLUSION: Based on this experience and a search of the literature, it is
      hypothesized that distraction osteogenesis is only a reliable reconstructive
      method in irradiated patients if the cumulative dose to the mandibular bone at
      the distraction site does not exceed a certain maximum still to be defined.

PMID- 15978824
TI  - Three-dimensional fetal cephalometry: an evaluation of the reliability of
      cephalometric measurements based on three-dimensional CT reconstructions and on
      dry skulls of sheep fetuses.
AB  - AIM: To develop a 3D CT cephalometric analysis for maxillary growth evaluation of
      sheep fetuses operated in utero, and to evaluate the reliability of this analysis
      by comparing it with a direct cephalometric analysis on dry skulls. MATERIAL AND
      METHODS: Five skulls of operated sheep fetuses were used, which after preparation
      were CT scanned and a 3D reconstruction was performed. A cephalometric analysis
      was performed directly on the dry skulls as well as on the reconstructed 3D CT
      images. In total, 56 linear distances were measured. In order to access the error
      of the method, the procedure was repeated after a 2 week interval. RESULTS: The
      comparison between the direct cephalometric and the 3D CT analysis revealed that
      only 5 variables were significantly different. The evaluation of the error of
      method revealed that 7 variables of the direct cephalometric analysis and none of
      the 3D CT analysis differed significantly. CONCLUSIONS: According to the results
      of this study, it can be concluded that a cephalometric analysis on 3D CT
      reconstructed images of the skulls includes fewer identification errors and seems
      to be an accurate and reliable method that could be regarded at least as
      equivalent to conventional cephalometry.

PMID- 15978826
TI  - Immunosuppressors and reversion of multidrug-resistance.
AB  - Drug resistance is the major reason for failure of cancer therapy. When one drug
      elicits a response in tumour cells resulting in resistance to a large variety of
      chemically unrelated drugs, this is called multidrug-resistance (MDR). ATP
      binding cassette (ABC) transporters contribute to drug resistance via ATP
      dependent drug efflux. P-glycoprotein (Pgp) encoded by MDR1 gene, confers
      resistance to certain anticancer agents. The development of agents able to
      modulate MDR mediated by Pgp and ABC transporters remained a major goal for the
      past 10 years. Immunosuppressors, cyclosporin A (CSA) in particular, were shown
      to modulate Pgp activity in laboratory models and entered very early into
      clinical trials for reversal of MDR. The proof of reversing activity of CSA was
      found in phase II studies with myeloma and acute leukaemia. In phase III studies,
      the results were less convincing regarding the response rate, progression-free
      survival and overall survival were detected in advanced refractory myeloma. The
      non-immunosuppressive derivative PSC833 was then extensively studied. This
      compound shows 10-fold higher potency in reversal of MDR mediated by Pgp. Results
      from clinical trials with this modulator are still emerging and the notable
      finding was the need to reduce the dose of anticancer agent used in combination
      with it. Other effects of CSA and PSC833 on MDR have been described. These two
      molecules have been shown to have an action on the metabolism of ceramide which
      stands as second messenger of anticancer agents-induced apoptosis. PSC833
      stimulates de novo ceramide synthesis and enhances cell death induced by
      anticancer agents, such as camptothecins and anthracyclines. In addition,
      ceramide glycosylation and storage in some cell lines have been described to play
      a crucial role in resistance to anticancer drugs. CSA is able to inhibit ceramide
      glucosylation and modulate MDR phenotype. The emergence of other modulators with
      several ABC protein targets like VX710 are of clinical interest in malignancies
      expressing several efflux pumps.

PMID- 15978827
TI  - Cancer incidence after immunosuppressive treatment following kidney
      transplantation.
AB  - Cancer incidence is increased in renal transplant recipients due to
      immunosuppressant treatment that should be maintained to prevent and treat acute
      rejection. Use of new and very potent immunosuppressants has made it possible to
      reduce acute rejection incidence and improve renal graft survival, although
      increase of infections and post-transplant neoplasms have become clearer. On the
      other hand, renal transplant candidates who remain on dialysis have a greater
      prevalence of neoplasms than the age-matched general population, either because
      the neoplasm was the cause of their renal failure (multiple myeloma or kidney or
      urinary tract cancers) or because their renal disease entails a risk for cancer
      development (acquired cystic disease or analgesic nephropathy). Practically, all
      de novo neoplasms have a greater incidence in renal transplant patients.
      Cutaneous neoplasms are the most prevalent in renal transplant recipients and
      their incidence increases with transplant time. Post-transplant
      lymphoproliferative diseases are more frequent in patients who receive greater
      immunosuppression (antithymocyte/antilymphocyte globulin or OKT3) or are infected
      de novo by Epstein Barr Virus (EBV) through the transplanted kidney. Kaposi's
      sarcoma has a high incidence in the renal transplanted population, does not
      appear in the general population, and is related with Human Herpes Virus 8 (HHV
      8) infections. The incidence of tumors in non-functioning native kidneys is
      especially high in renal transplant due to the presence of acquired cystic
      disease or analgesic nephropathy. Gold standards of post-transplant de novo renal
      neoplasm prevention are modulating immunosuppression and avoiding exposure to
      sunlight and to different oncogenic viruses (EBV, cytomegalovirus, hepatitis B
      and C viruses).

PMID- 15978828
TI  - Management of bone metastases in cancer: a review.
AB  - The presence of bone metastases is indicative of disseminated disease and
      typically indicates a short-term prognosis in cancer patients. Palliation of
      symptoms is the primary goal of therapy, with multidisciplinary efforts yielding
      the best results. New classes of drugs, such as bisphosphonates that
      significantly increase the time to first skeletal-related event (SRE), represent
      useful tools for the treatment of bone metastases. While the optimal duration of
      therapy needs to be defined, there is clinical benefit derived from the use of
      this class of agents. A potential role for bisphosphonates in the prevention of
      bone metastases is under current evaluation in clinical trials encompassing
      different solid tumor types. In combination with ongoing clinical trials, basic
      research to identify potential novel targets in the tumor cells-bone
      microenvironment will further define future strategies in the treatment of bone
      metastases.

PMID- 15978829
TI  - Screening for lung cancer: New horizons?
AB  - Lung cancer remains the leading cause of cancer-related deaths in the world. At
      present, the only high rate of cure therapy is surgical resection at early stage
      of disease. Early detection could potentially decrease lung cancer mortality
      suggesting that this cancer should be a good candidate for screening. Results of
      trials involving chest X-ray, sputum cytology and low-dose computed tomography
      (CT) are discussed here. The latter tool offers advantages over chest X-ray, but
      final results from controlled well conducted trials are necessary before the real
      utility of CT mass screening can be determined. Further approaches to secondary
      prevention such as screening with positron emission tomography (PET),
      autofluorescence bronchoscopy and biomarkers hold great promise for the future.

PMID- 15978830
TI  - Skin cancer and immunosuppression.
AB  - All immunosuppressive treatments, either pharmacological or physical, have the
      potential to impair the skin immune system network of cells and cytokines, thus
      leading to an increased incidence of skin cancer. Since skin cancer in transplant
      recipients may show uncommon clinical features and have an unusually aggressive
      course, transplant patients should be strictly followed up by experienced
      dermatologists in order to diagnose and treat properly any skin cancer in an
      early phase. Importantly, due to the fact that sun exposure increases
      immunosuppression in the skin, patients should be clearly informed about the
      additional risk of sun exposure and the preventive measures to be taken.

PMID- 15978831
TI  - Mechanisms of the self/non-self-survey in the defense against cancer: potential
      for chemoprevention?
AB  - When compared to a reference population, several large epidemiological studies
      with long-term follow-up have reported a three- to five-fold increased risk of
      neoplasia amongst patients who have received organ transplants, with an incidence
      curve that rises in a linear fashion with time. The relationship between the
      immune system and cancer is complex. The ability to discriminate "self" from "non
      self" is one of the central roles of the immune system. Since tumors arise from
      transformation of host cells, it is not surprising that some aspects of tumor
      immunity resemble autoimmunity. The immune response to tumors shares aspects of
      both self- and non-self-immune recognition. What accounts for the apparent
      failure of immunity? In this review article, we address the role of the self/non
      self-survey in the immune response to tumors, we describe mechanisms of immune
      surveillance against tumor cells, and we discuss models of ignorance, tolerance
      and tumor evasion of the immune response. The overall aim of the article is to
      demonstrate the scope for prevention of cancer in individuals at increased risk
      of developing malignancy due to immune compromise. Interventional strategies may
      involve the use of pro-differentiation agents such as retinoids, modifiers of
      polyamine biosynthesis or inhibitors of cyclooxygenase isozymes.

PMID- 15978832
TI  - Guidelines for the routine application of the peptide hits technique.
AB  - A set of guidelines has been developed for using the peptide hits technique (PHT)
      as a semi-quantitative screening tool for the identification of proteins that
      change in abundance in a complex mixture. The dataset that formed the basis for
      these experiments was created using a cell lysate derived from the yeast
      Saccharomyces cerevisiae, spiked at various levels with serum albumin (BSA), and
      analyzed by LC/MS/MS and SEQUEST. Knowing that the level of only one protein
      (BSA) actually changed in the mixture allowed for the development and refinement
      of the necessary bioinformatics and statistical analyses, e.g., principal
      component analysis (PCA), normalization, and analysis of variation (ANOVA). As
      expected, the number of BSA peptide hits changed in proportion to the amount of
      BSA added to the sample. PCA was able to clearly distinguish between the spiked
      samples and the untreated sample, indicating that PCA may be able to classify
      samples, e.g., healthy versus diseased, in future experiments. The use of an
      endogenous "housekeeping" protein was found to be superior to the use of total
      hits for data normalization prior to analysis. An ANOVA based model readily
      identified BSA as a protein of interest, that is, one likely to be changing from
      amongst the background proteins, indicating that an ANOVA model may be able to
      identify individual proteins in target or biomarker discovery experiments.
      General guidelines based on these combined observations are set forth for future
      analyses and the rapid screening for candidate proteins of interest.

PMID- 15978835
TI  - Gas-phase dissociation of oligoribonucleotides and their analogs studied by
      electrospray ionization tandem mass spectrometry.
AB  - Oligoribonucleotides (RNA) and modified oligonucleotides were subjected to low
      energy collision-induced dissociation in a hybrid quadrupole time-of-flight mass
      spectrometer to investigate their fragmentation pathways. Only very restricted
      data are available on gas-phase dissociation of oligoribonucleotides and their
      analogs and the fundamental mechanistic aspects still need to be defined to
      develop mass spectrometry-based protocols for sequence identification. Such
      methods are needed, because chemically modified oligonucleotides can not be
      submitted to standard sequencing protocols. In contrast to the dissociation of
      DNA, dissociation of RNA was found to be independent of nucleobase loss and it is
      characterized by cleavage of the 5'-P-O bond, resulting in the formation of c-
      and their complementary y-type ions. To evaluate the influence of different 2'
      substituents, several modified tetraribonucleotides were analyzed.
      Oligoribonucleotides incorporating a 2'-methoxy-ribose or a 2'-fluoro-ribose show
      fragmentation that does not exhibit any preferred dissociation pathway because
      all different types of fragment ions are generated with comparable abundance. To
      analyze the role of the nucleobases in the fragmentation of the phosphodiester
      backbone, an oligonucleotide lacking the nucleobase at one position has been
      studied. Experiments indicated that the dissociation mechanism of RNA is not
      influenced by the nucleobase, thus, supporting a mechanism where dissociation is
      initiated by formation of an intramolecular cyclic transition state with the 2'
      hydroxyl proton bridged to the 5'-phosphate oxygen.

PMID- 15978836
TI  - Phenotype and function of intestinal dendritic cells.
AB  - It is now appreciated that dendritic cells (DCs) play a primary role in oral
      tolerance and defense against mucosal pathogens. Specific DC subpopulations are
      localized to discrete regions within primary inductive tissues, like the Peyer's
      patch and mesenteric lymph node, and effector sites, like the lamina propria, and
      may have unique roles in driving regulatory, effector and memory T cell
      responses. Certain DC subpopulations may also help maintain T cell responses at
      sites of abnormal intestinal inflammation. While early in our understanding,
      knowledge about the involvement of DC subpopulations in the regulation of mucosal
      immunity may well provide a basis for the development of novel vaccines and
      therapeutics.

PMID- 15978837
TI  - Refolding and purification of recombinant OsNifU1A domain II that was expressed
      by Escherichia coli.
AB  - OsNifU1A is a NifU-like rice (Oryza sativa) protein, discovered recently. Its
      amino acid sequence is very homologous to the sequence of cyanobacterial CnfU and
      to the sequences of NifU C-terminal domains. Based on its sequence, OsNifU1A is
      probably a modular structure consisting of two CnfU-like domains, with domain I
      (formed by residues Leu73 to Gly153) and domain II (formed by residues Leu154 to
      Ser226). Domain I have a conserved Cys-X-X-Cys motif, which may function as an
      iron-sulfur cluster assembly scaffold. Domain II lacks a Cys-X-X-Cys motif and
      therefore, cannot function analogously. Other NifU-like proteins, with sequences
      homologous to OsNifU1A domain II, have been identified during plant genomic
      projects; however, the biological roles of these domains remain unknown. We
      successfully constructed an Escherichia coli expression system for OsNifU1A
      domain II that enabled us to synthesize and purify milligram quantities of
      protein for use in structural and functional studies. Using the Gateway system,
      we built DNA sequences corresponding to two OsNifU1A domain II fusion proteins.
      One construct has a (His)6 sequence upstream of the OsNifU1A domain II sequence;
      the other has an upstream thioredoxin-(His)6 sequence. Recombinant OsNifU1A
      domain II fusion proteins were extracted from E. coli inclusion bodies by
      dissolving them in 6 M guanidine-HCl. About 36% of the total (His)6/OsNifU1A
      domain II fusion protein initially present remained soluble after guanidine-HCl
      was completely removed by step-wise dialysis; whereas, recovery of soluble Trx
      (His)6 fusion protein was about 60% of the total cell lysate. About 2 mg of 15N
      labeled OsNifU1A domain II was purified for NMR spectral studies. Examination of
      the OsNifU1A domain II 1H-15N HSQC NMR spectrum indicated that the purified
      protein was monomeric and correctly folded. Therefore, we established an
      efficient procedure for synthesis and purification of 15N-labeled OsNifU1A domain
      II in quantities sufficient for heteronuclear NMR solution structure studies.

PMID- 15978838
TI  - Inflammatory cells of teleostean fish: a review focusing on mast
      cells/eosinophilic granule cells and rodlet cells.
AB  - In contrast to the roles played by monocytes/macrophages, neutrophils and
      lymphocytes, the presence and functions of basophils, mast cells/eosinophilic
      granule cells, eosinophils and rodlet cells in teleosts are areas of controversy.
      The tissue distribution of mast cells/eosinophilic granule cells in species from
      a certain genus shows a characteristic pattern, and this pattern is usually also
      present at the family level. Functionally, the mast cells/eosinophilic granule
      cells of teleosts show close similarity to the mast cells of mammals. Acute
      tissue damage is causing mast cell/eosinophilic granule cell degranulation and
      release of mediators of inflammation, whereas an increase in the number of these
      cells is often found in chronically inflamed tissues. The mast cells/eosinophilic
      granule cells of teleosts show marked diversity in their staining properties,
      with both basophilic and acidophilic components in their granules. In some fish
      families, e.g. the labrids, the eosinophilic component is dominating, whereas in
      the pike the granules are strongly basophilic and show the metachromatic staining
      characteristics found in the granules of mast cells, but being more akin to the
      granules of the mucosal than to those of the connective tissue type of mast cells
      of mammals. With respect to rodlet cells, a cell type hitherto clearly
      demonstrated only in teleosts, a characteristic distribution pattern seems to be
      established in certain families. In other families rodlet cells are absent in
      some individuals and present in different tissues in others. However, there is a
      close relation between the presence of helminths or other noxious agents and the
      presence of rodlet cells. Massive aggregations of such cells can be seen in
      affected epithelia of gills or the intestinal tract, and in individuals of
      species from some fish families they also occur in association with mesothelial
      and endothelial tissues. The rodlet cell may represent a type of eosinophilic
      granulocyte that populates the tissues at its immature stage and mature in
      response to the appropriate stimuli, in a way similar to that of mast cell
      precursors. Present evidence points to a functional role for the rodlet cells of
      teleosts in host defence against parasites.

PMID- 15978839
TI  - Male and female voices activate distinct regions in the male brain.
AB  - In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be
      perceived as gender-specific. Given that functional neuro-imaging correlates of
      AVHs involve multiple brain regions principally including auditory cortex, it is
      likely that those brain regions responsible for attribution of gender to speech
      are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and
      a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch
      scaled) male and female voice stimuli to test the hypothesis that male and female
      voices activate distinct brain areas during gender attribution. The perception of
      female voices, when compared with male voices, affected greater activation of the
      right anterior superior temporal gyrus, near the superior temporal sulcus.
      Similarly, male voice perception activated the mesio-parietal precuneus area.
      These different gender associations could not be explained by either simple pitch
      perception or behavioural response because the activations that we observed were
      conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The
      results of this study demonstrate that, in the male brain, the perception of male
      and female voices activates distinct brain regions.

PMID- 15978840
TI  - Towards quantification of blood-flow changes during cognitive task activation
      using perfusion-based fMRI.
AB  - Multi-slice perfusion-based functional magnetic resonance imaging (p-fMRI) is
      demonstrated with a color-word Stroop task as an established cognitive paradigm.
      Continuous arterial spin labeling (CASL) of the blood in the left common carotid
      artery was applied for all repetitions of the functional run in a quasi
      continuous fashion, i.e., it was interrupted only during image acquisition. For
      comparison, blood oxygen level dependent (BOLD) contrast was detected using
      conventional gradient-recalled echo (GE) echo planar imaging (EPI). Positive
      activations in BOLD imaging appeared in p-fMRI as negative signal changes
      corresponding to an enhanced transport of inverted water spins into the region of
      interest, i.e., increased cerebral blood flow (CBF). Regional differences between
      the localization of activations and the sensitivity of p-fMRI and BOLD-fMRI were
      observed as, for example, in the inferior frontal sulcus and in the intraparietal
      sulcus. Quantification of CBF changes during cognitive task activation was
      performed on a multi-subject basis and yielded CBF increases of the order of 20
      30%.

PMID- 15978842
TI  - Three-dimensional quantitative magnetisation transfer imaging of the human brain.
AB  - Quantitative magnetisation transfer (MT) analysis is based on a two-pool model of
      magnetisation transfer and allows important physical properties of the two proton
      pools to be assessed. A good signal-to-noise ratio (SNR) for the measured signal
      is essential in order to estimate reliably the parameters from a small number of
      samples, thus prompting the use of a sequence with high SNR, such as a three
      dimensional spoiled gradient acquisition. Here, we show how full brain coverage
      can be accomplished efficiently, using a three-dimensional acquisition, in a
      clinically acceptable time, and without the use of large numbers of slice
      selective radio-frequency pulses which could otherwise confound analysis. This
      acquisition was first compared in post mortem human brain tissue to established
      two-dimensional acquisition protocols with differing SNR levels and then used to
      collect data from six healthy subjects. Image data were fitted using the two pool
      model and showed negligible residual deviations. Quantitative results were
      assessed in several brain locations. Results were consistent with previous single
      slice data, and parametric maps were of good quality. Further investigations are
      needed to interpret the regional variation of quantitative MT quantities.

PMID- 15978841
TI  - Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter
      development in premature infants.
AB  - Diffusion tensor MRI (DTI) fiber tracking is the first non-invasive and in vivo
      technique for the delineation and quantitation of specific white matter pathways.
      In this study, quantitative fiber tracking was used to assess the structural
      development of the motor tract and somatosensory radiation in premature human
      newborns. These pathways are unmyelinated in the youngest premature infants and
      begin to myelinate during late preterm maturation. Previous studies have only
      been able to delineate parts of these pathways that could be manually outlined in
      2D based on anatomical landmarks. Furthermore, these previous studies could not
      separate motor and sensory regions. A high-sensitivity neonatal head coil was
      employed in conjunction with an MR-compatible incubator to perform high
      resolution imaging of the premature infant brain. The motor and somatosensory
      tracts were successfully delineated with 3D DTI fiber tracking in 37 exams of
      preterm newborns between 28 and 43 weeks gestational age. Both streamline
      deterministic and probabilistic methods were employed to perform quantitative
      fiber tractography. Tract-specific measurements of diffusion parameters including
      fractional anisotropy, directionally averaged diffusivity, and eigenvalues were
      obtained from the motor and sensory pathways. Using both deterministic and
      probabilistic fiber tracking, all tract-specific diffusion parameters were found
      to be significantly correlated with age and the motor tracts were found to have
      higher anisotropy and lower diffusivity than the sensory pathway. By segmenting
      the 3D fiber tracks by slice, measurements from different axial levels of the
      brain were found to vary with region and age. In summary, deterministic and
      probabilistic DTI fiber tracking methods were used to quantify the developmental
      changes of motor and somatosensory pathways in premature infants.

PMID- 15978843
TI  - The spatiotemporal pattern of auditory cortical responses during verbal
      hallucinations.
AB  - Functional magnetic resonance imaging (fMRI) studies can provide insight into the
      neural correlates of hallucinations. Commonly, such studies require self-reports
      about the timing of the hallucination events. While many studies have found
      activity in higher-order sensory cortical areas, only a few have demonstrated
      activity of the primary auditory cortex during auditory verbal hallucinations. In
      this case, using self-reports as a model of brain activity may not be sensitive
      enough to capture all neurophysiological signals related to hallucinations. We
      used spatial independent component analysis (sICA) to extract the activity
      patterns associated with auditory verbal hallucinations in six schizophrenia
      patients. SICA decomposes the functional data set into a set of spatial maps
      without the use of any input function. The resulting activity patterns from
      auditory and sensorimotor components were further analyzed in a single-subject
      fashion using a visualization tool that allows for easy inspection of the
      variability of regional brain responses. We found bilateral auditory cortex
      activity, including Heschl's gyrus, during hallucinations of one patient, and
      unilateral auditory cortex activity in two more patients. The associated time
      courses showed a large variability in the shape, amplitude, and time of onset
      relative to the self-reports. However, the average of the time courses during
      hallucinations showed a clear association with this clinical phenomenon. We
      suggest that detection of this activity may be facilitated by examining
      hallucination epochs of sufficient length, in combination with a data-driven
      approach.

PMID- 15978844
TI  - The effect of hypercapnia on the neural and hemodynamic responses to
      somatosensory stimulation.
AB  - Modern non-invasive imaging techniques utilize the coupling between neural
      activity and changes in blood flow, volume and oxygenation to map the functional
      architecture of the human brain. An understanding of how the hemodynamic response
      is influenced by pre-stimulus baseline perfusion is important for the
      interpretation of imaging data. To address this issue, the present study measured
      hemodynamics with optical imaging spectroscopy and laser Doppler flowmetry, while
      multi-channel electrophysiology was used to record local field potentials (LFP)
      and multi-unit activity (MUA). The response to whisker stimulation in rodent
      barrel cortex was recorded during baseline (normocapnia) and elevated perfusion
      rates produced by two levels of hypercapnia (5 and 10%). With the exception of
      the 'washout' of deoxyhemoglobin, which was attenuated, all aspects of the neural
      and hemodynamic response to whisker stimulation were similar during 5%
      hypercapnia to those evoked during normocapnia. In contrast, 10% hypercapnia
      produced cortical arousal and a reduction in both the current sink and MUA
      elicited by stimulation. Blood flow and volume responses were reduced by a
      similar magnitude to that observed in the current sink. The deoxyhemoglobin
      'washout', however, was attenuated to a greater degree than could be expected
      from the neural activity. These data suggest that imaging techniques based on
      perfusion or blood volume changes may be more robust to shifts in baseline than
      those based on the dilution of deoxyhemoglobin, such as conventional BOLD fMRI.

PMID- 15978845
TI  - Modulation of pain processing in hyperalgesia by cognitive demand.
AB  - The relationship between pain and cognitive function is of theoretical and
      clinical interest, exemplified by observations that attention-demanding
      activities reduce pain in chronically afflicted patients. Previous studies have
      concentrated on phasic pain, which bears little correspondence to clinical pain
      conditions. Indeed, phasic pain is often associated with differential or opposing
      effects to tonic pain in behavioral, lesion, and pharmacological studies. To
      address how cognitive engagement interacts with tonic pain, we assessed the
      influence of an attention-demanding cognitive task on pain-evoked neural
      responses in an experimental model of chronic pain, the capsaicin-induced heat
      hyperalgesia model. Using functional magnetic resonance imaging (fMRI), we show
      that activity in the orbitofrontal and medial prefrontal cortices, insula, and
      cerebellum correlates with the intensity of tonic pain. This pain-related
      activity in medial prefrontal cortex and cerebellum was modulated by the demand
      level of the cognitive task. Our findings highlight a role for these structures
      in the integration of motivational and cognitive functions associated with a
      physiological state of injury. Within the limitations of an experimental model of
      pain, we suggest that the findings are relevant to understanding both the
      neurobiology and pathophysiology of chronic pain and its amelioration by
      cognitive strategies.

PMID- 15978846
TI  - Effects of dopaminergic and serotonergic manipulation on emotional processing: a
      pharmacological fMRI study.
AB  - Recent neuroimaging studies have demonstrated abnormal central emotional
      processing in psychiatric disorders. The dopamine (DA) systems and serotonin (5
      HT) systems are the main target of psychopharmacotherapy. DA D2 receptor
      antagonists and selective serotonin reuptake inhibitors (SSRIs) are widely used
      in psychiatric practice. Investigating the effects of these drugs on emotional
      processing should lead to a better understanding of the pathophysiology and
      pharmacotherapy of neuropsychiatric disorders. We aimed to examine effects of
      dopaminergic and serotonergic manipulation on neural responses to unpleasant
      pictures in healthy volunteers using pharmacological fMRI. Thirteen healthy male
      subjects participated in a single-blind, randomized, placebo-controlled design
      study. Each subject participated in three fMRI sessions. In each session,
      participants were orally administered either 25 mg of sultopride or 50 mg of
      fluvoxamine or placebo prior to scanning, and neural responses to unpleasant and
      neutral pictures were recorded. Despite no significant differences being found in
      the subjective ratings of affective pictures across three sessions, compared to
      placebo, acute treatments of DA D2 receptor antagonists and SSRIs commonly
      attenuated the amygdala activity, although both treatments had slightly different
      modulatory effects on other components of the neural circuit of emotional
      processing. This study has shown that even acute treatment of drugs that
      manipulate neurotransmitter systems could affect brain activation associated with
      emotional processing in human brain. At the same time, our findings suggest that
      pharmacological fMRI could be a powerful tool for investigating the
      neurophysiological properties of drugs targeting neuropsychiatric disorders.

PMID- 15978847
TI  - Molecular phylogeny, evolutionary rates, and divergence timing of the symbiotic
      dinoflagellate genus Symbiodinium.
AB  - Symbiotic dinoflagellates belonging to the genus Symbiodinium are found in
      association with a wide variety of shallow-water invertebrates and protists
      dwelling in tropical and subtropical coral-reef ecosystems. Molecular phylogeny
      of Symbiodinium, initially inferred using nuclear ribosomal genes, was recently
      confirmed by studies of chloroplastic and mitochondrial genes, but with limited
      taxon sampling and low resolution. Here, we present the first complete view of
      Symbiodinium phylogeny based on concatenated partial sequences of chloroplast 23S
      rDNA (cp23S) and nuclear 28S-rDNA (nr28S) genes, including all known Symbiodinium
      lineages. Our data produced a well resolved phylogenetic tree and provide a
      strong statistical support for the eight distinctive clades (A-H) that form the
      major taxa of Symbiodinium. The relative-rate tests did not show particularly
      high differences between lineages and both analysed markers. However, maximum
      likelihood ratio tests rejected a global molecular clock. Therefore, we applied a
      relaxed molecular clock method to infer the divergence times of all extant
      lineages of Symbiodinium, calibrating its phylogenetic tree with the fossil
      record of soritid foraminifera. Our analysis suggests that Symbiodinium
      originated in early Eocene, and that the majority of extant lineages diversified
      since mid-Miocene, about 15 million years ago.

PMID- 15978848
TI  - Choice of cardiac tissue plays an important role in the evaluation of drug
      induced prolongation of the QT interval in vitro in rabbit.
AB  - INTRODUCTION: Regulatory guidelines (CPMP/986/96, ICHS7B) recommend the use of
      isolated cardiac tissues, including Purkinje fibers, papillary muscles and
      ventricular trabeculae, for detecting potential drug-induced long QT. However,
      the differential sensitivity of these tissues in experimental drug-induced long
      QT is relatively unknown. We investigated the electrophysiological
      characteristics of these tissue types in vitro together with their different
      responses to drugs that are known to induce prolongation of the QT interval in
      man. METHODS: Electrophysiological parameters were measured in vitro using a
      micro-electrode technique. The isolated rabbit Purkinje fibers, papillary muscles
      or ventricular trabeculae were superperfused with Tyrode's solution and
      stimulated according to different stimulation protocols. The effects of
      dofetilide (1 x 10(-8) M), sertindole (1 x 10(-6) M), erythromycin (3 x 10(-4) M)
      and sparfloxacin (1 x 10(-4) M) were evaluated relative to solvent (n=8 to 12 for
      each group). RESULTS: In isolated Purkinje fibers, action potential duration at
      90% repolarization (APD(90) at 1 Hz) was markedly prolonged by 55%
      (erythromycin), 103% (dofetilide), 118% (sertindole) and 88% (sparfloxacin) from
      baseline. The prolongation of APD(90) caused by these 4 compounds was associated
      with a 28% to 78% incidence of early afterdepolarizations (EADs) at 0.2 Hz only
      in the Purkinje fiber. In contrast, APD(90) was altered by erythromycin,
      dofetilide, sertindole and sparfloxacin only by +15%, +6%, -7% or +15%,
      respectively, in isolated papillary muscles, and by 33%, +28%, +4% or +16%,
      respectively, in ventricular trabeculae. EADs were not induced by these four
      compounds in papillary muscles or in trabeculae. Reducing the stimulation rate to
      0.2 Hz resulted in a 33% prolongation of APD(90) in Purkinje fibers, while
      APD(90) was shortened by 10% in papillary muscles and by 20% in ventricular
      trabeculae. CONCLUSION: The present study demonstrates that the differential
      sensitivity of tissue types play an important role in the detection of drug
      induced long APD and EADs. Indeed the Purkinje fiber was the only tissue type to
      display the well known phenomenon associated with I(kr) channel blockade (inverse
      use dependence), when the stimulation rate was decreased below 1 Hz. Rabbit
      Purkinje fibers constitute the most sensitive tissue type for detecting drug
      induced long action potential duration and EADs. As such the selection of tissue
      type needs to be taken into careful consideration in cardiac safety assessments
      when exploring drug induced long QT.

PMID- 15978849
TI  - Drug compliance of children and adolescents with epilepsy.
AB  - BACKGROUND: Compliance behavior depends on the specific clinical situation, the
      nature of the illness, and the treatment program. The aim of this study was to
      determine the rate of drug compliance in families caring for a child or
      adolescent with epilepsy and to describe some associated factors. METHODS: All
      the patients with epilepsy under 18 years of age who were attending the Motahary
      Clinic of Shiraz for a six-month period and their families were interviewed.
      RESULTS: The total number of participants was 181 patients. Drug compliance was
      satisfactory in 72.4% of the patients. Etiology of epilepsy, mono-therapy versus
      poly-therapy, duration of the disease, age of the patient, accompanying disease,
      parental smoking, parental education and living in urban versus rural areas did
      not significantly influence the drug compliance but maternal age was
      significantly higher in patients with poor compliance. Also, patients with
      positive family history of epilepsy had more noncompliance. Moreover, family size
      had a significant effect on drug compliance. Finally, patients using
      phenobarbital were more complaint than other patients. CONCLUSIONS: In this
      study, drug compliance was satisfactory in almost three-fourths of the patients
      with epilepsy. There was no significant association between noncompliance and the
      cause of epilepsy, duration of the disease, socio-economic status (parental
      smoking, living place, education) and number of drugs used to treat the illness.
      But paying attention to medication education for patients and parents, decreasing
      the complexity of the treatment regimen and younger possibly more motivated
      mothers in a small family, increased the drug compliance.

PMID- 15978850
TI  - A meta-analysis of sex differences prevalence, incidence and severity of
      osteoarthritis.
AB  - OBJECTIVE: To resolve uncertainty regarding sex differences in osteoarthritis
      (OA) by performing a meta-analysis of sex differences in OA prevalence, incidence
      and severity. METHODS: Standard search strategies for population-based studies of
      OA providing sex-specific data. Random effects meta-analysis to provide pooled
      male vs female risk and rate ratios for prevalent and incident OA, and
      standardized mean differences (SMD) for OA severity. Meta-regression was used to
      investigate sources of heterogeneity. RESULTS: Males had a significantly reduced
      risk for prevalent OA in the knee [Risk Ratio (RR) 0.63, 95% CI 0.53-0.75] and
      hand [RR 0.81, 95% CI 0.73-0.90] but not for other sites. Males aged <55 years
      had a greater risk of prevalent cervical spine OA [RR 1.29, 95% CI 1.18-1.41].
      Males also had significantly reduced rates of incident OA in the knee [Incidence
      Rate Ratio (IRR) 0.55, 95% CI 0.32-0.94] and hip [IRR 0.64, 95% CI 0.48-0.86],
      with a trend for hand [IRR 0.65, 95% confidence interval (CI) 0.35-1.20].
      Females, particularly those > or = 55 years, tended to have more severe OA in the
      knee but not other sites. Heterogeneity in the estimates of sex differences in
      prevalence was substantially explained by age and other study design factors
      including method of OA definition. CONCLUSIONS: The results demonstrate the
      presence of sex differences in OA prevalence and incidence, with females
      generally at a higher risk. Females also tend to have more severe knee OA,
      particularly after menopausal age. The site differences indicate the need for
      further studies to explore mechanisms underlying OA.

PMID- 15978851
TI  - Transposition of MINE, a composite retrotransposon, in the avirulence gene ACE1
      of the rice blast fungus Magnaporthe grisea.
AB  - The ACE1 avirulence gene allele from the rice blast fungus Magnaporthe grisea was
      characterized in virulent isolate 2/0/3, revealing the insertion of a 1.9 kb MINE
      retrotransposon in the last ACE1 exon. MINE is a novel chimeric element composed
      of a transcribed non-coding sequence of 1.1 kb (WEIRD) fused to a 5'-truncated
      MGL retrotransposon. MINEs were found in high copy number in M. grisea isolates
      from rice (68 copies) and as a single copy in isolate CD156 from Eleusine. MINEs
      vary in size (1.3-6.7 kb) with conserved 5' WEIRD sequences and variable 3' MGL
      sequences. MGLs fused to WEIRDs correspond to different 5'-truncated MGLs with
      conserved 3' ends. The organization and diversity of MINEs suggest that these
      retrotransposons result from independent fusions between WEIRD and 5'-truncated
      MGLs. Such chimera could be formed during MGL reverse transcription as proposed
      for human U6-LINE1 chimeric retrotransposons and integrated into M. grisea genome
      using MGL machinery.

PMID- 15978852
TI  - What is the prevalence and economic impact of chlamydial infections in cattle?
      The need to validate and harmonise existing methods of detection.

PMID- 15978853
TI  - Cardiac syncope from occult transposition masquerading as convulsive epilepsy.
AB  - A four-year-old boy on Valproate therapy for a presumed diagnosis of epilepsy
      presented with a recurrence of tonic spasms. A history of precipitation of these
      episodes with exercise prompted a search for an underlying cardiac disorder. The
      child was ultimately diagnosed to have corrected transposition of great arteries
      with 2:1 atrioventricular block. This case illustrates that cardiac syncope due
      to underlying congenital heart disease can masquerade as epilepsy in children.

PMID- 15978854
TI  - Review of aetiological concepts of temporomandibular pain disorders: towards a
      biopsychosocial model for integration of physical disorder factors with
      psychological and psychosocial illness impact factors.
AB  - Several studies have reported that musculoskeletal disorders of the
      stomatognathic system, commonly known as temporomandibular disorders (TMD)
      resemble musculoskeletal disorders and chronic pain disorders in general. There
      is also general consensus that combined biomedical and biopsychosocial methods
      best support the assessment and management of the cardinal features of TMD, i.e.,
      pain and dysfunction or physical (peripheral) and psychosocial (central) factors.
      This overview of the aetiology of TMD will outline conceptualizations of past
      models and present the current view that patients with TMD should be assessed
      according to both the physical disorder and the psychosocial illness impact
      factors. The conceptual theories outlined in this review include biomedical
      models related to temporomandibular joints, muscles of mastication and occlusal
      factors, psychological models and the biopsychosocial models. An integrated and
      multidimensional approach concerning physical and psychosocial factors in
      temporomandibular pain and dysfunction is presented as an example of how the
      biopsychosocial model and information processing theory may apply in the
      conceptualization and management of TMD for various health care professionals.

PMID- 15978855
TI  - Spatially resolved emulsion droplet sizing using inverse Abel transforms.
AB  - Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) is well established
      as a tool for determining emulsion droplet-size distributions via measurement of
      restricted self-diffusion. Most measurements made to date have not been spatially
      resolved, but have measured an average size distribution for a certain volume of
      emulsion. This paper demonstrates a rapid method of performing spatially
      resolved, restricted diffusion measurements, which enables emulsion droplet
      sizing to be spatially resolved as a function of radius in cylindrical geometries
      or pipes. This is achieved by the use of an Abel transform. The technique is
      demonstrated in various annular systems containing two emulsions, with different
      droplet-size distributions, and/or a pure fluid. It is also shown that by
      modifying the pulse sequence by the inclusion of flow-compensating magnetic field
      gradients, the technique can measure spatially resolved droplet-size
      distributions in flowing emulsions, with potential applications in spatially
      resolved on-line droplet-size analysis.

PMID- 15978856
TI  - Lack of association between certain candidate gene polymorphisms and the
      metabolic syndrome.
AB  - The goal of the present study was to assess the association between the metabolic
      syndrome (MS) and certain polymorphisms in genes involved in lipid transport,
      insulin resistance, intramitochondrial energy transport, appetite control,
      vasomotor tone, and adipocyte differentiation. The sample was composed of 601 men
      and 594 women aged 35-64 years recruited in the north of France that were
      genotyped for the following polymorphisms (SNPs): uncoupling protein, UCP3 -55
      C/T; fatty acid transport protein, FATP1 intron 8 +48 G/A; tumor necrosis factor,
      TNF-alpha -308 G/A; leptin, LEP 5'UTR +19 G/A; and beta3 subunit of G proteins,
      GNB3 C825T. Waist girth, plasma triglycerides, HDL-cholesterol, glucose and
      systolic, and diastolic blood pressure were used to define the MS according to
      the National cholesterol education program (NCEP-III) guidelines. There were 155
      (27.4%) men and 124 (21.8%) women who satisfied the NCEP-III criteria and 855
      control subjects. By logistic regression using a dominant model (homozygous for
      the common allele versus carriers of the rare allele), the odds ratio [95%
      confidence interval] for the MS were: 0.91 [0.68-1.22] for FATP1, 0.93 [0.68
      1.28] for TNF-alpha, 0.97 [0.73-1.29] for UCP3, 1.06 [0.80-1.40] for LEP, and
      1.12 [0.84-1.48] for GNB3 SNPs. There was no evidence for a gender-specific
      effect. In conclusion, this study suggests that among a large sample of French
      men and women, the above named SNPs in UCP3, FATP1, TNF-alpha, LEP, and GNB3
      genes are not major contributors to the MS risk.

PMID- 15978857
TI  - Impact of time-limited feeding and dietary carbohydrate content on weight loss in
      group-housed cats.
AB  - Twenty-four adult cats were transitioned to time-limited feeding and randomized
      to either a dry low carbohydrate diet (LC) or a dry reduced energy diet (HC). In
      Trial 1 the LC and HC groups received equal amounts of food (by weight) for 13
      weeks. Both groups consumed all food offered, hence the LC group received more
      energy/day than the HC group. In Trial 2 all cats were fed the LC diet for 12
      weeks, but each group received the energy that the opposite group had received in
      Trial 1. In Trial 1 only the overweight HC cats (body condition score> 6/9)
      experienced a significant change in body weight (-0.52 +/- 0.08 kg). In Trial 2,
      LC/Low Calorie overweight cats lost 0.62 +/- 0.10 kg, whereas, the LC/High
      Calorie normal weight cats gained 0.68 +/- 0.05 kg. In conclusion, body condition
      and energy intake but not type of diet influenced weight in this cohort of group
      housed cats.

PMID- 15978858
TI  - Experience with microvascular free flaps in preoperatively irradiated tissue of
      the oral cavity and oropharynx in 303 patients.
AB  - This study examined free flap reconstruction of surgical defects of the oral
      cavity and oropharynx after preoperative radiochemotherapy. Included in this
      analysis are 303 prospectively followed patients who underwent a multimodal
      treatment regime for advanced oral and oropharyngeal carcinoma. All patients
      received preoperative radiochemotherapy (Mitomycin C, 5-FU, 50 Gy), ablative
      surgery, and primary free flap reconstruction. Patient characteristics, surgical
      parameters like duration of surgery and ischaemia, size of defect, type of
      transplant, and clinical outcome parameters like duration of intensive care and
      hospitalization, type of complications, necessity and type of revision surgery
      were statistically evaluated. Overall flap success rate was 93.1%. Sixty seven
      patients required revision and 21 flaps (6.9%) were lost. Overall complication
      rate was 22.1%. Mean duration of intensive care (DOIC) and duration of overall
      postoperative hospitalization (DOH) were 11.0+/-9.6 days and 35.9+/-26.3 days,
      respectively. Flap success and flap related complications after 50 Gy focal
      radiation dosage were found in a comparable range as in published series of
      reconstructions in uncompromised tissue.

PMID- 15978859
TI  - Methylation of tumor suppressor genes p16(INK4a), p27(Kip1) and E-cadherin in
      carcinogenesis.
AB  - Not only genomic mutations but also abnormal epigenetic methylation can
      significantly contribute to gene silencing and carcinogenesis. Methylation is
      particularly often observed in the CpG islands of the promoter regions in the
      regulatory genes. However, there are considerable differences in the incidence of
      methylation e.g. in the tumor suppressor genes, so that aberrant methylation of
      p16(INK4a) is relatively frequently observed in tumors, p27(Kip1) methylation is
      rare, and the incidence of E-cadherin methylation occurs at an intermediate rate.
      Although true genomic defects are generally much less common than methylation,
      parallel tendencies for both are often observed, probably reflecting the
      different levels of evolutionary advantage for tumor cells from inactivation of
      different genes. This also suggests that loss of p27 expression could be more a
      consequence of carcinogenesis, while lost p16 expression is a true oncogenic
      event. Due to the role of p27 in maintaining cellular quiescence, however, loss
      of its expression can still be a useful partial indicator of the aggressiveness
      of cancer. Loss of E-cadherin or its catenin partners of cellular adhesion will
      result in increasing invasiveness and metastatic potential of neoplastic cells
      but, because of several alternative routes to the same effect, incidence of lost
      expression for one component gene like E-cadherin does not need to be very high.
      Similarly, there must be a relatively high number of genes with modest or low
      incidence of aberrant silencing by methylation, to reflect multiple alternatives
      for the multistep process of carcinogenesis. Nevertheless, methylation of
      different genes also shows characteristic differences between different cancer
      and tumor types, and the epigenetic methylation patterns therefore have
      considerable diagnostic and prognostic potential. Realising this potential
      requires efficient methods for profiling the status of methylation. Such
      profiling methods have only recently become available and are still under
      relatively rapid development.

PMID- 15978860
TI  - Synthesis, spectroscopic and redox properties of the copper(II) complexes of N
      (di-methylphenyl)-3,5-Bu2t-salicylaldimines.
AB  - A series of copper(II) complexes (CuL2x) with new N-di-methylphenyl-3,5-Bu2t
      salicylaldimines (L(x)H) were prepared and characterized by IR, UV/vis, 1H NMR,
      ESR, cyclic voltammetry techniques and chemical oxidation. L(x)H ligands have
      been found selectively bind to a Cu(II), rather than to Ni(II), Co(II), Mn(II),
      VO(IV), Zn(II) and Cd(II). ESR examinations of the CuL2x complexes demonstrate
      that they exist in magnetically diluted mononuclear or coupled triplet-state
      structures in the solid. The temperature dependent (113-283 K) intensity of the
      powder ESR spectra for some CuL2x is characteristic of ferromagnetic coupling (J
      > 0). The reduction potentials of CuL2x in DMSO are sensitive to aniline
      moieties. Chemical oxidation of CuL2x with (NH4)2[Ce(NO3)6] in CHCl3 and MeCN
      solutions at 300 K affords gradually disappearance of their ESR signals and
      dramatic changes in the electronic spectra as well as the appearance of new
      maximum bands at 530-672 (CHCl3) and 670-700 nm (MeCN), suggesting generation of
      Cu(II)-phenoxyl radical species.

PMID- 15978861
TI  - Photoinduced amino-imino tautomerization reaction in 2-aminopyrimidine and its
      methyl derivatives with acetic acid.
AB  - The electronic absorption and fluorescence spectra of 2-aminopyrimidine (2APM), 2
      amino-4-methylpyrimidine (2A4MPM), and 2-amino-4,6-dimethylpyrimidine (2ADMPM)
      with acetic acid (AcOH) were measured in isooctane (2,2,4-trimethylpentane) at
      room temperature. From the absorption spectra, a hydrogen-bonded complex
      formation of the 2APM/AcOH, 2A4MPM/AcOH, and 2ADMPM/AcOH systems was recognized
      in isooctane. The enthalpy changes (-DeltaH) for the complex formation were
      estimated to be ca. 41.2-45.1 kJ mol-1 and increased in proportion to the numbers
      of the methyl group introduced into the 2APM. The -DeltaH values refer to the
      formation of the hydrogen-bonded 1:1 complex between the ring nitrogen atom and
      NH2 group of the aminopyrimidine and the OH and CO groups of AcOH, respectively.
      In the 2A4MPM/AcOH double hydrogen-bonded complex the OH group of AcOH is thought
      to be linked to the ring nitrogen at the 1-postion of 2A4MPM. The fluorescence
      spectral results indicate that the double proton transfer reaction takes place
      during the excited state, and gives rise to an imino-tautomer vibration emission,
      from analogy with the fluorescences of 1-methyl-2(1H)-pyrimidinimine (MPMI), 1,4
      dimethyl-2(1H)-pyrimidinimine (DMPMI), and 1,4,6-trimethyl-2(1H)-pyrimidinimine
      (TMPMI). The fluorescence quantum yields of the imino-tautomers also increased in
      proportion to the numbers of the methyl group introduced into the 2APM.

PMID- 15978862
TI  - GEORAMAN 2004. Proceedings of the 6th International Conference on Raman
      Spectroscopy Applied to the Earth and Planetary Sciences, June 6-11, 2004,
      Honolulu, Hawaii, USA.

PMID- 15978863
TI  - The interaction between ketamine and some crown ethers in common organic solvents
      studied by NMR: the effect of donating atoms and ligand structure.
AB  - 1H NMR spectroscopy was used to investigate the stoichiometry and stability of
      the drug ketamine cation complexes with some crown ethers, such as 15-crown-5
      (15C5), aza-15-crown-5 (A15C5), 18-crown-6 (18C6), aza-18-crown-6 (A18C6), diaza
      18-crown-6 (DA18C6), dibenzyl-diaza-18-crown-6 (DBzDA18C6) and cryptant [2,2,2]
      (C222) in acetonitrile (AN), dimethylsulfoxide (DMSO) and methanol (MeOH) at 27
      degrees C. In order to evaluate the formation constants of the ketamine cation
      complexes, the CH3 protons chemical shift (on the nitrogen atom of ketamine) was
      measured as function of ligand/ketamine mole ratio. The formation constant of
      resulting complexes were calculated by the computer fitting of chemical shift
      versus mole ratio data to appropriate equations. A significant chemical shift
      variation was not observed for 15C5 and 18C6. The stoichiometry of the mono aza
      and diaza ligands are 1:1 and 1:2 (ligand/ketamine), respectively. In all of the
      solvents studied, DA18C6 formed more stable complexes than other ligands. The
      solvent effect on the stability of these complexes is discussed.

PMID- 15978864
TI  - Synthesis, spectral characterisation of 2-(5-methyl-1H-benzimidazol-2-yl)-4
      bromo/nitro-phenols and their complexes with zinc(II) ion, and solvent effect on
      complexation.
AB  - 2-(5-Methyl-1H-benzimidazol-2-yl)-4-bromo/nitro-phenols (HLBr and HLNO2) and
      their Zn(II) complexes with ZnX2 (X = Cl, I, NO3) were synthesized and
      characterized by elemental analysis, molar conductivity, IR, 1H and 13C NMR
      spectra. The OH proton appears near the NH protons in the 1H NMR spectra of the
      ligands because of the strong intramolecular hydrogen bonding between the OH
      hydrogen and the C=N nitrogen atoms. The complexation is investigated in ethanol
      and isopropanol and it is observed that isopropanol is a better solvent than
      ethanol for the complex forming. HLBr gives harder complexation reaction with
      Zn(II) according to HLNO2 because of the stronger intramolecular hydrogen bonding
      in HLBr, and the both ligands react easier with Zn(NO3)2 than ZnCl2 and ZnI2. The
      Zn(II) complexes of HLBr have 1:1 M:L ratio and ionic character, however, HLNO2
      give a non-ionic complex that has 1:2 M:L ratio. In the complexes the phenolic
      hydrogen is eliminated and a chelate structure is formed.

PMID- 15978865
TI  - UV-vis spectroscopic study of interaction of metal ions with the E(T)(30) dye
      involving micellar media.
AB  - Interaction between 3d-transition metal ions (Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+
      and Zn2+) and the E(T)(30) dye, 2,6-diphenyl-4-(2,4,6-triphenyl 1
      pyridino)phenolate in aqueous medium have been studied by distributing the dye
      between the aqueous and micellar phase formed by cationic surfactant
      cetyltrimethylammonium bromide(CTAB). Values of equilibrium constant K for the
      dye-metal ion interaction and the partition coefficient of the dye between the
      micellar and the aqueous phase have been determined. K values show a systematic
      correlation with ionic potential of metal ions.

PMID- 15978866
TI  - Solvent influence on the photophysical properties of 4-methoxy-N-methyl-1,8
      naphthalimide.
AB  - 4-Methoxy-N-methyl-1,8-naphthalimide (1) exhibits considerable solvatochromism
      and its UV-vis spectral properties have been studied in several polar/non-polar
      and protic/aprotic solvents, as well as in ethanol-water mixtures. The results
      reveal a strong influence of the solvent's polarity and its hydrogen-bond donor
      (HBD) capability on the photophysical properties of 1. For binary ethanol/water
      mixtures, preferential solvation models describe the band shifts in the probe's
      visible absorption spectrum well, but they fail to describe the corresponding
      shifts of the emission maxima. Pseudolinear approximations between solvent
      composition and molecule's transition energies, E(T), can be used to study the
      composition of ethanol-water mixtures, simplifying the mathematical treatment for
      eventual analytical applications.

PMID- 15978867
TI  - Photoelectron spectra and electronic structures of some chlorosulfonyl
      pseudohalides.
AB  - The electronic structures of chlorosulfonyl pseudohalide ClSO2X (X = Cl, NCO, N3)
      are studied by photoelectron spectroscopy (PES) combined with the OVGF
      calculation at 6-311++G(3df) basis sets. The first ionization potentials for
      ClSO2NCO and ClSO2N3 are determined to be 12.02 and 11.43 eV, respectively, for
      the first time, and their features in the PE spectra were assigned based on
      comparison with related compounds and with high level quantum calculations.
      Photoelectron spectra of ClSO2NCO and ClSO2N3 suggest that the interactions
      between chlorine "lone-pair" electrons and two pseudohalogen groups have
      significant effect on the HOMOs of two compounds, besides the influence of their
      electronegativity on the first ionization energies.

PMID- 15978868
TI  - Conduction electron spin resonance of small silver particles.
AB  - Electron spin resonance (ESR) spectroscopy has been used to study the conduction
      electron spin resonance (CESR) of small silver particles stabilized in dehydrated
      Ag-rho zeolite. Silver particles were produced by hydrogen reduction at elevated
      temperatures and diameter of the stabilized particles was calculated based on the
      linewidth of CESR signal using Kawabata theory.

PMID- 15978869
TI  - Spectral analysis of Mn2+, Co2+ and Ni2+: B2O3-ZnO-PbO glasses.
AB  - This paper reports on the spectral properties of Mn2+, Co2+ and Ni2+ ions doped
      B2O3-ZnO-PbO glasses. XRD, FT-IR spectra and DSC profiles of these glasses have
      also been carried out, and the FT-IR profiles have shown the presence of both BO3
      and BO4 units. It is interesting to notice that the FT-IR peak positions are
      slightly shifted towards higher energy with an increase in transition metal ion
      concentration change. From the measured DSC thermograms, glass transition (T(g)),
      crystallization (T(c)) and temperature of melting (T(m)) have been evaluated.
      From the UV absorption spectra of Mn2+, Co2+ and Ni2+ ions doped glasses, both
      direct and indirect optical band gaps have been calculated. The visible
      absorption spectra of Mn2+:glasses have shown a broad absorption band at 520 nm
      (6A1g(S) --> 4T1g(G)); with Co2+ ions one absorption band at 605 nm (4A2(4F) -->
      4T1(4P)) and another at 1450 nm (4A2(4F) --> 4T1(4F)); and for Ni2+:glasses three
      absorption bands at 420 nm (3A2g(F) --> 3T1g(P)), 805 nm (3A2g(F) --> 1Eg(D)) and
      880 nm (3A2g(F) --> 3T1g(F)) have been observed. For Mn2+:glasses, upon
      excitation with 262 nm, a green emission (539 nm) with a slight blue shift; and
      with 392 nm, a green emission (534 nm) with a slight red shift with Mn2+ ions
      concentration change (0.2-0.5 mol%) has been observed. This green emission has
      been assigned to (4T1(G) --> 6A1(S)) d-d transition of Mn2+ ions that are in
      tetrahedral co-ordination. For 0.5 mol% Co2+ ions doped glass, upon excitation
      with 580 nm, a red emission (625 nm) has been observed which originates from
      2E(2G) --> 4A2(4F) transition of Co2+ ions in tetrahedral co-ordination. For Ni2+
      ions doped glasses upon excitation with 420 nm, a green (577 nm) and red (670 nm)
      emissions are observed and are assigned to (1T2g(D) --> 3A2g(F)) and (1T2g(D) -->
      3T2g(F)) d-d transitions of Ni2+ ions in octahedral co-ordination.

PMID- 15978870
TI  - DFT and IR spectroscopic analysis of p-tert-butylthiacalix[4]arene.
AB  - Vibrational analysis of p-tert-butylthiacalix[4]arene based on an experimental
      mid and far IR spectra is described here. Density functional calculations of a
      most stable cone conformer related to crystalline solid FT-IR spectra in the
      temperature range up to 180 degrees C as well spectra of dilute solution have
      been used to obtain a better understanding of conformational state and a hydrogen
      bonding of p-tert-butylthiacalix[4]arene. Complete assignments were made for
      experimental FT-IR spectra of the cone conformer. Heating (up to 180 degrees C)
      of crystalline p-tert-butylthiacalix[4]arene did not change both conformational
      and cooperative H-bonding state of its molecules. A temperature spectral effect
      seems to be due to some relaxation of crystal packing mostly viewed on the OH
      bands.

PMID- 15978871
TI  - Hemodynamic features and impaired arterial oxygenation in patients with
      portopulmonary hypertension.
AB  - Portopulmonary hypertension (P-PHT) is sporadically found in cirrhosis patients
      who have portal hypertension. We retrospectively investigated the clinical
      features of six patients with P-PHT and compared their hemodynamics and arterial
      oxygenation with data from 60 cirrhosis patients without pulmonary hypertension
      (non-PHT cirrhosis) admitted to our department. The mean pulmonary artery
      pressure and pulmonary vascular resistance index of P-PHT patients ranged from 25
      to 57mmHg and from 399 to 1405dynesscm(-5)m(-2), respectively, and their arterial
      oxygenation was impaired. The systemic vascular resistance and cardiac index of P
      PHT patients were similar level to those of patients with non-PHT cirrhosis. We
      found 10 patients with non-PHT cirrhosis in whom pulmonary vascular resistance
      exceeded the critical level for pre-capillary pulmonary hypertension
      (120dynesscm(-5)). These patients showed a distinctive hemodynamic profile,
      including a decrease of cardiac output due to contraction of the plasma volume
      and resultant elevation of systemic vascular resistance. However, the decrease of
      cardiac output contributed little to the elevation of pulmonary vascular
      resistance. Our findings suggested that certain factor(s) were acting to raise
      pulmonary vascular tone in these patients, which might cause chronic damage to
      the pulmonary vascular bed, leading to the onset of pulmonary hypertension.

PMID- 15978872
TI  - A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma
      Assessment of enhancement patterns on dynamics computed tomography before
      resection.
AB  - BACKGROUND AND AIM: : The aim of this study was to identify computed tomography
      features that contribute to clinical diagnosis of hepatocellular
      cholangiocarcinoma. METHODS: : We retrospectively reviewed the clinicopathologic
      features of 11 patients who underwent hepatectomy for hepatocellular
      cholangiocarcinoma between January 1994 and December 2003 at Hiroshima City
      Hospital and investigated correlation of histopathologic features of surgical
      specimens with preoperative enhanced computed tomography findings. RESULTS: :
      Three computed tomography enhancement patterns were observed: an area of
      hyperenhancement in the early phase and hypoenhancement due to washout of
      contrast medium in the late phase, resembling hepatocellular carcinoma (Type I,
      n=4); peripheral enhancement in the early and late phases (Type II, n=2); an area
      of hyperenhancement in the early phase and an area of slight delayed enhancement
      in the late phase (Type III, n=4). Histopathologically, all tumors were of mixed
      morphology (Allen's Type C) comprising hepatocellular carcinoma and
      cholangiocarcinoma components with transitional features. Computed tomography
      findings conformed well to pathologic findings. The hepatocellular carcinoma
      component was predominant in Type I masses. Type II masses showed central
      necrosis. In Type III masses, the hepatocellular carcinoma-predominant component
      corresponded to the area of early-phase enhancement and the cholangiocarcinoma
      predominant component to the area of late-phase enhancement. CONCLUSIONS: : In
      Type III tumors, hepatocellular and cholangiocellular components can be
      identified on the basis of dynamic computed tomography enhancement pattern.

PMID- 15978873
TI  - Postmitotic nuclear retention of episomal plasmids is altered by DNA labeling and
      detection methods.
AB  - One often overlooked aspect of nonviral gene therapy is the maintenance and
      localization of plasmids within a transfected cell. In this study we have
      quantified the nuclear retention of plasmids within microinjected cells after a
      single round of cell division. We employed several commercially available
      reagents to label plasmids with fluorophores for our microinjection tracking
      experiments. Interestingly, plasmids labeled with different techniques produced
      drastically different results. Naked plasmids microinjected directly into nuclei
      and later detected by in situ hybridization were found almost exclusively within
      the nuclei of the daughter cells after mitosis and were partitioned between the
      daughter nuclei with a normal, Gaussian distribution. Identical results were
      obtained with plasmids labeled with a fluorescent peptide nucleic acid. However,
      when plasmids were labeled with several commercially available fluorescent DNA
      labeling kits that randomly attach fluorophores to the entire plasmid and
      injected into HeLa cell nuclei, the modified plasmids were excluded from daughter
      nuclei after cell division. Taken together, these results suggest that naked,
      unmodified plasmids are retained in the nucleus following cell division and
      likely continue to express in the daughter cells. Our results demonstrate the
      significant alterations in episome localization that the labeling technique
      itself can have on plasmid trafficking.

PMID- 15978874
TI  - Epilepsy-associated stigma in sub-Saharan Africa: the social landscape of a
      disease.
AB  - Many studies in developed regions of the world have confirmed that stigma
      contributes substantially to the psychological and social burden of epilepsy.
      Relatively few studies of epilepsy-associated stigma have been conducted in
      Africa, where much of the world's burden of epilepsy exists. In sub-Saharan
      Africa (SSA), particularly in rural regions, close family ties, communal living
      situations, and traditional belief systems undoubtedly influence the expression
      of stigmatization. A review of the epidemiologic, anthropologic, and sociologic
      studies of epilepsy in SSA provides significant insights into how people with
      epilepsy (PWE) are perceived by their communities and families and how these
      perceptions translate into limited social and economic opportunities and possibly
      worsen the physical vulnerability of PWE in this region. The medical community is
      not exempt from the social process of stigmatization, and poor public health
      infrastructure and medical services undoubtedly contribute to the cycle of
      epilepsy-associated stigma through wide treatment gaps, poor seizure control, and
      high rates of seizure-related injury. In this review, we extrapolate data from
      existing studies of epilepsy in SSA coupled with our own experience providing
      epilepsy care in the region to give an overview of the social landscape of this
      common, devastating condition.

PMID- 15978875
TI  - Toward a framework for understanding lay public's comprehension of disaster and
      bioterrorism information.
AB  - In the last decade, we have witnessed a significant increase in disaster
      preparedness and crisis communication efforts. This stands in sharp contrast with
      paucity of research that deals with the public's comprehension of disaster
      information and related decision-making. The objective of this paper is to
      outline a theoretical and methodological framework for research on lay
      comprehension of crisis information. The proposed framework integrates two bodies
      of research: (1) cognitive science literature on comprehension and decision
      making and (2) studies of the effects of anxiety on performance. The paper
      reviews selected works and methods from both fields, discussing how cognitive
      perspective could be extended to include emotional factors. We also discuss how
      further research integrating the proposed framework with public health
      communication perspective could: (1) provide insights for developing effective
      disaster communication and (2) inform the development of technological support
      for disaster communication and for education of lay people and health
      professionals.

PMID- 15978876
TI  - Carotid sinus nerve responses and ventilatory acclimatization to hypoxia in adult
      rats following 2 weeks of postnatal hyperoxia.
AB  - Adult rats have decreased carotid body volume and reduced carotid sinus nerve,
      phrenic nerve, and ventilatory responses to acute hypoxic stimulation after
      exposure to postnatal hyperoxia (60% O2, PNH) during the first 4 weeks of life.
      Moreover, sustained hypoxic exposure (12%, 7 days) partially reverses functional
      impairment of the acute hypoxic phrenic nerve response in these rats. Similarly,
      2 weeks of PNH results in the same phenomena as above except that ventilatory
      responses to acute hypoxia have not been measured in awake rats. Thus, we
      hypothesized that 2-week PNH-treated rats would also exhibit blunted
      chemoafferent responses to acute hypoxia, but would exhibit ventilatory
      acclimatization to sustained hypoxia. Rats were born into, and exposed to PNH for
      2 weeks, followed by chronic room-air exposure. At 3-4 months of age, two studies
      were performed to assess: (1) carotid sinus nerve responses to asphyxia and
      sodium cyanide in anesthetized rats and (2) ventilatory and blood gas responses
      in awake rats before (d0), during (d1 and d7), and 1 day following (d8) sustained
      hypoxia. Carotid sinus nerve responses to i.v. NaCN and asphyxia (10 s) were
      significantly reduced in PNH-treated versus control rats; however, neither the
      acute hypoxic ventilatory response nor the time course or magnitude of
      ventilatory acclimatization differed between PNH and control rats despite similar
      levels of PaO2 . Although carotid body volume was reduced in PNH rats, carotid
      body volumes increased during sustained hypoxia in both PNH and control rats. We
      conclude that normal acute and chronic ventilatory responses are related to
      retained (though impaired) carotid body chemoafferent function combined with
      central neural mechanisms which may include brainstem hypoxia-sensitive neurons
      and/or brainstem integrative plasticity relating both central and peripheral
      inputs.

PMID- 15978877
TI  - Type 2 diabetes--therapy with dipeptidyl peptidase IV inhibitors.
AB  - The sole application of an inhibitor of the dipeptidyl peptidase DP IV (also DP
      4, CD26, DPP-IV or DPP-4) to a mammal subsequently leading to improved glucose
      tolerance marks a major breakthrough in metabolic research bearing the potential
      of a new revolutionary diabetes therapy. This was demonstrated in rat applying
      the specific DP IV inhibitor isoleucyl thiazolidine. It was published in 1996 for
      the first time that a specific DP IV inhibitor in a given dose was able to
      completely block glucagon-like peptide-1 (GLP-1) degradation in vivo resulting in
      improved insulin response accompanied, by accelerated peripheral glucose
      disposal. Later on, these results were confirmed by several research teams
      applying DP IV inhibitors intravenously or orally. Today, the DP IV inhibition
      for the treatment of metabolic disorders is a validated principle. Now, more than
      10 years after the initial animal experiments, first DP IV inhibitors as
      investigational drugs are tested in phase 3 clinical trials.

PMID- 15978878
TI  - Nutritional state and energy balance in cirrhotic patients with or without
      hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in
      Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).
AB  - BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients
      admitted to 10 Italian Gastroenterology Units were included in a prospective
      study to evaluate nutritional state and energy balance in liver cirrhosis.
      MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the
      total population, while adequacy of calorie intake versus measured total energy
      expenditure was evaluated in a comparable subpopulation and in 40 matched
      controls, by computing the energy balance. RESULTS: Our data demonstrated that:
      (i) malnutrition was present in 25% of the total patients and significantly
      correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of
      malnutrition is influenced by mBEE: normometabolic patients exhibit a significant
      (p<0.005) reduction of mid-arm fat area while both hypermetabolic and
      hypometabolic patients show a significant (p<0.005) decline in kg of free fat
      mass; (iii) normometabolic and hypometabolic patients have a negative energy
      balance, due to a high level of physical activity (127+/-14 kJ) in the first
      group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second;
      (iv) hypermetabolic patients have a positive energy balance due to decreased
      daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and
      normometabolic patients eat a significantly (p<0.05) reduced percentage of
      protein whereas malnourished and hypermetabolic patients eat a significantly
      increased percentage of fat (p<0.05). CONCLUSION: Although multivariate
      regression analysis confirms that the Child-Pugh's score is a better independent
      predictor of malnutrition, the measure of REE, TEE, calorie intake and energy
      balance need to be routinely performed in cirrhotic patients, in order to
      recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom
      the nutritional and metabolic parameters are indispensable as a basis for
      designing and prescribing personalised nutritional strategies that can treat
      muscle malnutrition and thus improve the morbidity and mortality rates.

PMID- 15978879
TI  - Looking at what you see, a coeliac face.

PMID- 15978880
TI  - Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in
      osteoblastic MC3T3-E1 cells.
AB  - Ghrelin is a 28-amino-acid peptide identified in the stomach as an endogenous
      ligand of the growth hormone secretagogue receptor (GHS-R) that strongly
      stimulates the release of growth hormone at the hypothalamus and pituitary level.
      Although GHS-Rs are expressed in a variety of peripheral tissues, little is known
      about its effect on bone independent of GH/IGF-1 axis. This study was undertaken
      to investigate whether ghrelin exerts a direct effect on osteoblasts. We
      identified mRNA and protein expression of GHS-R in primary osteoblasts as well as
      a number of osteoblastic cell lines, including MC3T3-E1, ROS 17/2.8, UMR-106,
      MG63, and SaOS2 cells. Treatment of ghrelin (10(-11) to 10(-7) M) to MC3T3-E1
      cells showed dose-dependent stimulation of proliferation, which was abrogated by
      treatment with [d-Lys]-GHRP-6 (10(-3) M), a selective antagonist of the ghrelin
      receptor. Ghrelin activated ERK1/2 MAPK and pretreatment with MAPK kinase
      inhibitors, PD98059 attenuated the ghrelin-induced cell proliferation. Ghrelin
      also inhibited TNFalpha-induced apoptosis and suppressed caspase-3 activation
      that occurs in response to TNFalpha as well as during in vitro differentiation
      process. Moreover, ghrelin treatment enhanced in vitro osteoblast differentiation
      as evidenced by matrix mineralization, alkaline phosphatase activity, and
      osteoblast-specific gene expression. These results suggest that ghrelin promotes
      proliferation and differentiation and inhibits apoptosis of osteoblasts.

PMID- 15978881
TI  - Metabolic activation of the nontricyclic antidepressant trazodone to
      electrophilic quinone-imine and epoxide intermediates in human liver microsomes
      and recombinant P4503A4.
AB  - Therapy with the antidepressant trazodone has been associated with several cases
      of idiosyncratic hepatotoxicity. While the mechanism of hepatotoxicity remains
      unknown, it is possible that reactive metabolites of trazodone play a causative
      role. Studies were initiated to determine whether trazodone undergoes
      bioactivation in human liver microsomes to electrophilic intermediates. LC/MS/MS
      analysis of incubations containing trazodone and NADPH-supplemented microsomes or
      recombinant P4503A4 in the presence of glutathione revealed the formation of
      conjugates derived from the addition of the sulfydryl nucleophile to mono
      hydroxylated- and hydrated-trazodone metabolites. Product ion spectra suggested
      that mono-hydroxylation and sulfydryl conjugation occurred on the 3-chlorophenyl
      ring, whereas hydration and subsequent sulfydryl conjugation had occurred on the
      triazolopyridinone ring system. These findings are consistent with bioactivation
      sequences involving: (1) aromatic hydroxylation of the 3-chlorophenyl-ring in
      trazodone followed by the two-electron oxidation of this metabolite to a reactive
      quinone-imine intermediate, which reacts with glutathione in a 1,4-Michael
      fashion and (2) oxidation of the pyridinone ring to an electrophilic epoxide,
      ring opening of which, by glutathione or water generates the corresponding
      hydrated-trazodone-thiol conjugate or the stable diol metabolite, respectively.
      The pathway involving trazodone bioactivation to the quinone-imine has also been
      observed with many para-hydroxyanilines including the structurally related
      antidepressant nefazodone. It is proposed that the quinone-imine and/or the
      epoxide intermediate(s) may represent a rate-limiting step in the initiation of
      trazodone-mediated hepatotoxicity.

PMID- 15978882
TI  - The management of infants and children for painless imaging.
AB  - The ability of a child to remain sufficiently immobile for painless imaging
      depends upon their behaviour and the imaging itself. Anaesthesia allows imaging
      to be optimised but it is expensive, scarce and inappropriate for many
      situations. Fortunately, sedation and behavioural techniques are sufficiently
      successful for the majority of scanning, and success rates are high provided that
      suitable children are selected. Sedation, however, administered by non
      anaesthetists, may have catastrophic complications such as airway obstruction.
      Current UK recommendations demand that any sedation technique has a 'wide margin
      of safety', but in addition to this, safety is dependent on trained, skillful and
      experienced staff. Magnetic resonance imaging frightens many children and special
      planning is necessary for sedation and anaesthesia. When planning an imaging
      service for children, all the management techniques should be considered in order
      to achieve maximum efficiency, quality and safety.

PMID- 15978883
TI  - Diagnostic imaging in undergraduate medical education: an expanding role.
AB  - Radiologists have been involved in anatomy instruction for medical students for
      decades. However, recent technical advances in radiology, such as multiplanar
      imaging, "virtual endoscopy", functional and molecular imaging, and spectroscopy,
      offer new ways in which to use imaging for teaching basic sciences to medical
      students. The broad dissemination of picture archiving and communications systems
      is making such images readily available to medical schools, providing new
      opportunities for the incorporation of diagnostic imaging into the undergraduate
      medical curriculum. Current reforms in the medical curriculum and the
      establishment of new medical schools in the UK further underline the prospects
      for an expanding role for imaging in medical education. This article reviews the
      methods by which diagnostic imaging can be used to support the learning of
      anatomy and other basic sciences.

PMID- 15978884
TI  - Spectrum of angiographic findings in aortoarteritis.
AB  - Angiographic appearances are characteristic, distinctive and a major basis of
      established criteria in the diagnosis of aortoarteritis. We present a pictorial
      review of digital subtraction angiography imaging in patients with proven
      aortoarteritis, based upon 16 years' experience in our institution. Understanding
      of these angiographic appearances is important for definitive diagnosis, and for
      evaluation of the extent of the disease in order to plan appropriate further
      management.

PMID- 15978885
TI  - Is direct radiologist supervision of abdominal computed tomography (CT) scans
      necessary?

PMID- 15978886
TI  - Is direct radiologist supervision of abdominal computed tomography (CT) scans
      necessary?
AB  - AIM: To determine the effect of direct radiological supervision of patients
      attending for abdominal CT by assessing the frequency of protocol alteration
      subsequent to radiologist review of the images obtained. MATERIALS AND METHODS: A
      prospective questionnaire-based observational study was performed of 187
      consecutive patients undergoing abdominal CT. The CT protocol was determined by a
      radiologist in advance, with reference to the request form. Any subsequent change
      in the prescribed study that was contingent on radiologist review of the images
      obtained was documented on the questionnaire. Comparison was made with a second
      (control) group of 100 patients undergoing cranial CT. RESULTS: A protocol change
      was undertaken following radiologist review of the CT images of 17 (9%) of the
      group undergoing abdominal CT, compared with 14 (14%) of the group undergoing
      cranial CT. In the abdominal CT group, further scanning was performed for lesion
      characterization, to guide a subsequent interventional procedure, because of
      inadequate anatomical coverage or to evaluate an unexpected lung tumour. There
      was no significant difference in proportions between the two groups (p=0.23).
      CONCLUSION: When abdominal and cranial CT studies were compared, there was no
      significant difference in the proportion of studies requiring a change in the
      prescribed protocol following radiologist review of the images obtained. There
      was no evidence to suggest that abdominal CT was any less suited to protocol.

PMID- 15978887
TI  - Evaluation of clinical and MR findings for the prognosis of spinal epidural
      haematomas.
AB  - AIM: The potential of MR and clinical findings of spinal epidural haematomas
      (SEHs), particularly the early MR findings, to help minimize delays in diagnosis,
      to aid prognosis and as a reference for conservative treatment, are evaluated.
      METHODS: Retrospectively 20 patients with SEHs (14 men and 6 women) were examined
      to record their neurological deficit, MR findings, management, clinical outcome,
      and interval between symptom onset and MRI or surgery. Two-tailed Fisher's exact
      test was used for these analyses. RESULTS: Of 8 patients with severe neurological
      deficit at the onset of symptoms, none had obvious clinical improvement after
      either surgical or conservative management. Of 12 patients with mild to moderate
      deficits, 11 (92%) showed improvement or recovery of clinical symptoms. T2
      weighted images revealed myelopathy or infarction of the compressed spinal cord
      in 9 patients, 7 (78%) of whom had no improvement in neurological deficit with
      either conservative or surgical management. Images in 6 patients showed contrast
      enhancement in the haematomas. CONCLUSION: Poor clinical outcomes were observed
      mainly in those with severe neurological deficit and hyperintensity on T2
      weighted images of the involved spinal cord. Surgery did not appear to improve
      outcome in many of these patients. In acute SEHs, MRI showed characteristic
      findings, such as contrast enhancement, which should not be confused with signs
      of inflammatory or neoplastic epidural disease.

PMID- 15978889
TI  - A combination of small bowel imaging methods: conventional enteroclysis with
      complementary magnetic resonance enteroclysis.
AB  - AIM: The aim of this prospective study was to evaluate the overall findings of
      conventional enteroclysis (CE) with complementary magnetic resonance enteroclysis
      (MRE) in small bowel disease. METHODS: The study included 32 patients referred
      from various clinical departments, with known or suspected small bowel disease
      and abnormalities on CE. Immediately after CE, true fast imaging with steady
      state precession (true FISP), and unenhanced and gadolinium-enhanced T1-weighted
      fast low-angle shot (FLASH) sequences with fat saturation were obtained. Mucosal,
      mural and luminal changes of the small bowel were evaluated by each technique. In
      addition, bowel wall thickening, bowel wall enhancement and perienteric changes
      were assessed by MRE. The radiological findings obtained were evaluated together
      as a combination, and the role of MRE in the determination of the activity and
      complications of the small bowel disease was assessed. Radiological findings were
      correlated with clinical evaluation and follow-up in all cases, including
      endoscopy in 14 cases and surgery in 5 cases. RESULTS: MRE provided important
      supplementary mural and extramural information, including degree of pathological
      wall thickness, mural enhancement pattern associated with disease activity,
      perivisceral collection, abscess formation, mesenteric fibrofatty proliferation,
      lymphadenopathy and increase in perienteric vascularity. Short strictures were
      not revealed on MRE; however, for patients with a history of abdominal
      malignancy, MRE helped characterize the level of any obstruction and the extent
      of the disease. CONCLUSION: We recommend MRE for patients who have findings of
      advanced inflammatory bowel disease or neoplasm on CE examination. The
      combination of these two techniques can provide important information on the
      degree and extent of the disorder.

PMID- 15978888
TI  - Preoperative evaluation of live renal donors using multislice CT angiography.
AB  - AIM: To determine the accuracy of multidetector row CT renal angiography in the
      preoperative evaluation of live kidney donors, and to identify potential pitfalls
      when reporting. METHODS: Between July 1998 and June 2003, 74 consecutive live
      renal donors underwent contrast-enhanced multidetector row CT renal angiography
      before donor nephrectomy. The operative notes and radiological reports of all
      cases were reviewed retrospectively. Where a significant discrepancy was
      identified, the archived images were reviewed by two radiologists in the light of
      the intraoperative findings. RESULTS: A total of 12 discrepancies were identified
      in 11 of the 74 cases (15%). In the preoperative CT angiography reports, 4
      accessory arteries, 6 early-branching renal arteries, 1 duplicated renal vein and
      1 accessory ureter were not identified; 9 of these were evident on review, but
      were not detected at the time of reporting. In 3 cases (1 accessory artery, the
      duplicated renal vein and the accessory ureter), the anomaly was not visible on
      review of the CT angiographic data, even with the benefit of hindsight. Surgical
      feedback during the study period resulted in modifications to CT technique and
      improved performance. CONCLUSION: In the majority of cases, there was good
      correlation between preoperative CT renal angiography and operative findings.
      Most discrepancies were due either to an oversight by the reporting radiologist,
      or failure to fully appreciate the potential surgical significance of certain
      findings. Regular surgical feedback plays a valuable role in improving reporting
      accuracy and maintaining imaging standards.

PMID- 15978890
TI  - Comparative evaluation of magnetization transfer contrast and fluid attenuated
      inversion recovery sequences in brain tuberculoma.
AB  - AIM: To compare T1-weighted magnetization transfer (MT) with fluid attenuated
      inversion recovery (FLAIR) imaging for evaluating conspicuity and number of
      lesions in individuals with brain tuberculoma. MATERIALS AND METHODS: In all 28
      patients with brain tuberculoma underwent MR examination using fast spin-echo
      (FSE) T2, spin-echo (SE) T1, T1-weighted MT and FLAIR imaging. Post-contrast T1
      weighted MT imaging was taken as the gold standard for assessing the number of
      lesions. Tuberculomas detected both on T1-weighted MT and FLAIR imaging were
      examined for the wall to be defined, and were divided into two groups on the
      basis of presence (group 1) or absence (group 2) of perilesional oedema visible
      on FLAIR imaging. The mean signal intensity of the wall of the lesions and
      adjacent oedema or brain parenchyma was analyzed qualitatively and
      quantitatively. RESULTS: The number of lesions detected on T1-weighted MT was
      higher than on FLAIR imaging (209 versus 163). Conspicuity in both groups was
      better on T1-weighted MT images qualitatively as well as quantitatively. The
      difference in the signal intensity of the wall of the lesion and perilesional
      oedema was statistically significant only on T1-weighted MT images in group 1
      (p=0.0003 versus 0.3), whereas in group 2 it was statistically significant both
      on T1-weighted MT and FLAIR imaging (p=0.009 versus 0.05). CONCLUSION: FLAIR
      imaging is not helpful in the examination of brain tuberculomas compared with T1
      weighted MT imaging, as it neither contributes to the characterization of lesion
      nor assesses the true disease load.

PMID- 15978891
TI  - US correlation for MRI-detected breast lesions in women with familial risk of
      breast cancer.
AB  - AIM: To examine the value of US correlation for MRI-detected breast lesions in
      women with familial risk of breast cancer. METHODS: From an initial dataset of
      245 women with positive family history who had breast cancer surveillance
      involving mammography or MRI between November 1994 and February 2001, 179
      subjects with follow-up data were selected. A total of 43 women with 48 MRI
      detected lesions underwent further assessment with US. Histopathological
      correlation was available from 38 breast biopsies performed for 33 women.
      RESULTS: Sonographic correlates were identified in 32 (66.7%) of the 48 MRI
      detected lesions, with cancer present in 11 (34.4%) of these. This compares with
      1 (6.3%) cancer found in the 16 lesions without sonographic correlates. Of the 12
      malignant lesions, 11 (91.7%) had sonographic correlates whereas 21 (58.3%) of
      the 36 benign lesions had sonographic correlates. In all 74% of breast biopsies
      were performed under US guidance compared with 8% under MRI guidance. The
      proportion of MRI- and US-correlated benign and malignant lesions undergoing US
      guided biopsy were 85.7% and 90.9%, respectively. CONCLUSION: The probability of
      cancer was significantly higher in MRI-detected breast lesions with sonographic
      correlates compared with those without such correlation. The advantage of
      convenient biopsy under US guidance as opposed to MRI guidance highlights the
      value of sonographic assessment of MRI-detected breast lesions.

PMID- 15978893
TI  - Height does not predict ureteric length.
AB  - AIM: To establish whether ureteric length correlates with an individual's height.
      METHOD: A prospective study was performed involving 25 patients. The height of
      each participant was determined, and also actual ureteric length by direct
      measurement using a ureteric catheter. Simple regression analyses were carried
      out, using a p value of 0.05 as the level of significance. RESULTS: Height did
      not correlate with the actual ureteric length (p=0.54). CONCLUSION: Height does
      not predict obstructed ureteric length.

PMID- 15978892
TI  - Accuracy of reporting of intravenous urograms: a comparison of radiographers with
      radiology specialist registrars.
AB  - AIM: To evaluate whether uroradiographers trained to do so can interpret
      intravenous urograms as accurately as radiology specialist registrars (SpRs).
      METHODS: A total of 150 consecutive IVU examinations were prospectively assessed.
      The preliminary reporter (a uroradiographer, or an SpR in years 1 to 4) wrote a
      provisional report on each, and all the IVUs were subsequently assessed by an
      experienced uroradiologist blinded to the provisional report. The
      uroradiologist's report was taken as the standard. Comparisons between the
      provisional reports and the standard were made by Pearson chi-squared test
      (chi(2)). RESULTS: Data were available for 149 IVUs. In comparison with the
      standard report, 1st year SpRs interpreted the IVU series with an accuracy of
      76%; the combined group of 2nd, 3rd and 4th year SpRs achieved an accuracy of
      88%, whereas the uroradiographers demonstrated an accuracy of 92%. Overall, the
      difference was to be statistically significant (p=0.021), with a linear trend for
      increased accuracy with increased experience being highly significant (p=0.006).
      CONCLUSION: The uroradiographers significantly outperformed all the SpRs from
      years 1 to 4, achieving 92% accuracy in interpretation compared with an
      experienced consultant uroradiologist.

PMID- 15978894
TI  - Diabetic nephropathy with acute symmetrical changes in the basal ganglia regions.

PMID- 15978895
TI  - Dual ectopic thyroid.

PMID- 15978896
TI  - Neuroimaging in non-accidental head injury: if, when, why and how.

PMID- 15978898
TI  - The imaging of intussusception.

PMID- 15978899
TI  - Metastatic manifestations of invasive lobular breast carcinoma.

PMID- 15978900
TI  - A functional role of the C-terminal 42 amino acids of SUR2A and SUR2B in the
      physiology and pharmacology of cardiovascular ATP-sensitive K(+) channels.
AB  - The ATP-sensitive K(+) (K(ATP)) channel is composed of four pore-forming Kir6.2
      subunits and four sulfonylurea receptors (SUR). Intracellular ATP inhibits K(ATP)
      channels through Kir6.2. SUR is an ABC protein bearing transmembrane domains and
      two nucleotide-binding domains (NBD1 and NBD2). SUR increases the open
      probability of K(ATP) channels by interacting with ATP and ADP through NBDs and
      with K(+) channel openers such as nicorandil through its transmembrane domain.
      Because NBDs and the drug receptor allosterically interact with each other,
      nucleotides and drugs probably activate K(ATP) channels by causing the same
      conformational change of SUR. SUR2A and SUR2B have the identical drug receptor
      and NBDs and differ only in the C-terminal 42 amino acids (C42). Nonetheless,
      nicorandil ~100 times more potently activates SUR2B/Kir6.2 than SUR2A/Kir6.2
      channels. Based on our allosteric model, we have analyzed the interaction between
      NBDs and the drug receptor in SUR2A and SUR2B and found that both nucleotide
      bound NBD1 and NBD2 more strongly induce the conformational change in SUR2B than
      SUR2A. Therefore, C42 modulates the function of not only NBD2 which is close to
      C42 in a primary structure but NBD1 which is more than 630 amino acid N-terminal
      to C42. This raises the possibility that in the presence of nucleotides, NBD1 and
      NBD2 dimerize to induce the conformational change and that the dimerization
      enables C42 to gain access to both NBDs. Modulation of the nucleotide-NBD1 and 
      NBD2 interactions by C42 would determine the stability of the nucleotide
      dependent dimer and thus, the physiological and pharmacological properties of
      K(ATP) channels.

PMID- 15978902
TI  - Function and distribution of the SUR isoforms and splice variants.
AB  - Alternative splicing allows multiple mRNAs to be generated from a single gene,
      which in turn can be translated into a group of diverse proteins with different
      roles and structures. The outcome of alternative splicing leads to the co
      existence of multiple splice variants of a gene at different concentrations in
      different tissues. The pore-forming subunit of the K(ATP) channel (K(IR)6.x) and
      the regulatory sulfonylurea receptor (SUR(x)) subunits exist in a 4:4
      stoichiometry to form hetero-octameric ATP-sensitive potassium channel (K(ATP))
      channels, which are widely distributed in various types of tissues at either the
      plasma membrane (cellK(ATP)) or mitochondrial inner membrane (the mitochondrial
      form of K(ATP) channel, mitoK(ATP)). They perform important physiological
      functions in regulating insulin secretion in pancreatic beta-cells, providing
      ischemic protection in heart and brain, and regulating vascular tone in smooth
      muscles. Two separate genes, the regulatory subunit protein I (SUR1) and the
      regulatory subunit protein II (SUR2) encode the high- and low-affinity SUR,
      respectively. This review summarizes the current studies on the function and
      distribution of the SUR isoforms and alternative splice variants, and to a lesser
      extent the K(IR)6.x subunits. The different isoforms and splice variants allow
      for many K(ATP) channel combinations, and therefore, increases the channel
      diversity and the possibility of complexity in function.

PMID- 15978903
TI  - Sarcolemmal K(ATP) channels: what do we really know?
AB  - K(ATP) channels are present at an extremely high density in the heart, and we
      know from in vitro studies that channel activation causes dramatic action
      potential shortening and contractile failure. But, if and when this happens in
      vivo is still a matter of debate. Twenty one years of intense study have led to a
      well-developed understanding of the molecular basis of K(ATP) channel activity.
      Structure-function studies, together with cellular experiments probing regulatory
      molecules have told us much about the way the K(ATP) channel can activate, and
      gene-targeting and proteomic tools have further elucidated determinants of in
      vivo function. However, the true physiological determinants of sarcolemmal K(ATP)
      activity remain elusive, we still await full illumination of the role of the
      channel in the intact heart.

PMID- 15978901
TI  - Mitochondrial K(ATP) channels in cell survival and death.
AB  - Since the discovery of the mitochondrial ATP-sensitive potassium channel
      (mitoK(ATP)) more than 13 years ago, it has been implicated in the processes of
      ischemic preconditioning (IPC), apoptosis and mitochondrial matrix swelling.
      Different approaches have been employed to characterize the pharmacological
      profile of the channel, and these studies strongly suggest that cellular
      protection well correlates with the opening of mitoK(ATP). However, there are
      many questions regarding mitoK(ATP) that remain to be answered. These include the
      very existence of mitoK(ATP) itself, its degree of importance in the process of
      IPC, its response to different pharmacological agents, and how its activation
      leads to the process of IPC and protection against cell death. Recent findings
      suggest that mitoK(ATP) may be a complex of multiple mitochondrial proteins,
      including some which have been suggested to be components of the mitochondrial
      permeability transition pore. However, the identity of the pore-forming unit of
      the channel and the details of the interactions between these proteins remain
      unclear. In this review, we attempt to highlight the recent advances in the
      physiological role of mitoK(ATP) and discuss the controversies and unanswered
      questions.

PMID- 15978904
TI  - Regulation of the ATP-sensitive K channel Kir6.2 by ATP and PIP(2).
AB  - ATP-sensitive K (K(ATP)) channels are blocked by ATP and activated by PIP(2).
      Both negatively-charged ligands are presumed to bind to positively-charged
      residues on the N-and C-termini of the channel's cytoplasmic domain. Evidence
      summarized here suggests that the channel's interaction with ATP and PIP(2) is
      regulated by separate groups of residues, involving both direct charge-charge
      interactions and allosteric effects. ATP interaction is regulated by R50 in the N
      terminus and by K185, R192 and R201 in the C-terminus. R192 and R201 mutations
      decrease channel sensitivity to ATP, ADP and AMP to a similar extent, implying
      that they regulate interaction with either the alpha phosphate group, common to
      all three adenine nucleotides, or the adenosine moiety. K185 mutations, and to a
      lesser extent R50 mutations, decrease ATP and ADP sensitivity without markedly
      affecting AMP sensitivity, implying that they regulate interaction with the beta
      phosphate of ATP and ADP. In addition, when open probability decreases due to
      rundown, ATP sensitivity increases in R50, K185 and R192, but not in R201
      mutants. Combining these observations with recent structural data, we hypothesize
      the following scenario: 1) the ATP binding site is located at the outside of the
      channel's cytoplasmic domain away from the pore. 2) When the channel is open, R50
      and K185 interact directly with the beta phosphate of ATP, whereas R192, which
      appears to be removed from the ATP binding site, modulates the initial
      interaction with ATP allosterically. 3) When the channel closes, R201 is in
      position to interact with the alpha phosphate of ATP to stabilize the closed
      state. 4) PIP(2) also interacts with the channel's cytoplasmic domain, but at
      distinct positively-charged residues located above the ATP binding site and near
      to the plasma membrane. These residues include R54 in the N-terminus and R176,
      R177 and R206 in the C-terminus. Thus, the binding domains of ATP and PIP(2) in
      the N- and C-termini do not appear to overlap.

PMID- 15978905
TI  - K(ATP) channels "vingt ans apres": ATG to PDB to Mechanism.
AB  - A multidisciplinary effort over twenty years has provided deep insight into the
      nature of K(ATP) channels. First discovered in cardiomyocytes and pancreatic beta
      cells, as ubiquitous sensors of the ADP/ATP ratio they are implicated in multiple
      disorders characterized by the uncoupling of excitation from metabolism. Composed
      of two disparate subunits these large octameric channels present a formidable
      challenge to scientists interested in understanding mechanism in physical,
      chemical, and structural terms. Post-cloning studies have defined the domains and
      interactions, within and between the nucleotide-inhibited K(IR) pore and
      nucleotide-stimulated, drug-binding core of the ATP-Binding Cassette (ABC)
      regulatory subunits, that control channel assembly and gating. Determination of
      the three-dimensional structures of the bacterial prototypes of the channel
      subunits allowed homology modeling and has provided increasingly detailed
      mechanistic understanding. Here I review the early electrophysiology and
      molecular biology of K(ATP) channels, cover biophysical principles governing
      their single channel kinetics, integrate this with current efforts to understand
      ligand-recognition and gating within the pore and SUR core, and propose a
      mechanism of coupling based on recent identification of a SUR gatekeeper module
      and first composite models of (SUR/K(IR) 6.0)(4) complexes. This mechanism, based
      on interactions between inter-K(IR) subunit ATP-binding pockets and a unique bi
      directional regulatory apparatus comprised of elements from the gatekeeper and
      K(IR) amino terminus, provides a molecular perspective for understanding the
      biophysical basis underlying the polar effects of pathogenic mutations in K(ATP)
      channel subunits.

PMID- 15978906
TI  - Child survival: countdown to 2015.

PMID- 15978907
TI  - Saving the lives of vulnerable children.

PMID- 15978908
TI  - Endovascular aneurysm repair: important mid-term results.

PMID- 15978909
TI  - Paternal postnatal depression: fathers emerge from the wings.

PMID- 15978910
TI  - Stroke epidemiology in the developing world.

PMID- 15978911
TI  - Hodgkin's disease: are you the type?

PMID- 15978912
TI  - Upper gastrointestinal alarms: the 2-week rule.

PMID- 15978914
TI  - What is the Royal Society for?

PMID- 15978915
TI  - What is the Royal Society for?

PMID- 15978916
TI  - What is the Royal Society for?

PMID- 15978917
TI  - Neonatal screening for inborn errors of metabolism.

PMID- 15978918
TI  - Indigenous rabies in the UK.

PMID- 15978919
TI  - Neonatal screening for inborn errors of metabolism.

PMID- 15978920
TI  - Transmission of infections during commercial air travel.

PMID- 15978921
TI  - Local luck.

PMID- 15978922
TI  - Dilemma over forced treatment.

PMID- 15978923
TI  - Nutcracker.

PMID- 15978924
TI  - Treatments for paediatric femoral fractures.

PMID- 15978925
TI  - Endovascular aneurysm repair versus open repair in patients with abdominal aortic
      aneurysm (EVAR trial 1): randomised controlled trial.
AB  - BACKGROUND: Although endovascular aneurysm repair (EVAR) has a lower 30-day
      operative mortality than open repair, the long-term results of EVAR are
      uncertain. We instigated EVAR trial 1 to compare these two treatments in terms of
      mortality, durability, health-related quality of life (HRQL), and costs for
      patients with large abdominal aortic aneurysm (AAA). METHODS: We did a randomised
      controlled trial of 1082 patients aged 60 years or older who had aneurysms of at
      least 5.5 cm in diameter and who had been referred to one of 34 hospitals
      proficient in the EVAR technique. We assigned patients who were anatomically
      suitable for EVAR and fit for an open repair to EVAR (n=543) or open repair
      (n=539). Our primary endpoint was all-cause mortality, with secondary endpoints
      of aneurysm related mortality, HRQL, postoperative complications, and hospital
      costs. Analyses were by intention to treat. FINDINGS: 94% (1017 of 1082) of
      patients complied with their allocated treatment and 209 died by the end of
      follow-up on Dec 31, 2004 (53 of aneurysm-related causes). 4 years after
      randomisation, all-cause mortality was similar in the two groups (about 28%;
      hazard ratio 0.90, 95% CI 0.69-1.18, p=0.46), although there was a persistent
      reduction in aneurysm-related deaths in the EVAR group (4%vs 7%; 0.55, 0.31-0.96,
      p=0.04). The proportion of patients with postoperative complications within 4
      years of randomisation was 41% in the EVAR group and 9% in the open repair group
      (4.9, 3.5-6.8, p<0.0001). After 12 months there was negligible difference in HRQL
      between the two groups. The mean hospital costs per patient up to 4 years were UK
      pound sterling 13,257 for the EVAR group versus pound sterling 9946 for the open
      repair group (mean difference pound sterling 3311, SE 690). INTERPRETATION:
      Compared with open repair, EVAR offers no advantage with respect to all-cause
      mortality and HRQL, is more expensive, and leads to a greater number of
      complications and reinterventions. However, it does result in a 3% better
      aneurysm-related survival. The continuing need for interventions mandates ongoing
      surveillance and longer follow-up of EVAR for detailed cost-effectiveness
      assessment.

PMID- 15978926
TI  - Endovascular aneurysm repair and outcome in patients unfit for open repair of
      abdominal aortic aneurysm (EVAR trial 2): randomised controlled trial.
AB  - BACKGROUND: Endovascular aneurysm repair (EVAR) to exclude abdominal aortic
      aneurysm (AAA) was introduced for patients of poor health status considered unfit
      for major surgery. We instigated EVAR trial 2 to identify whether EVAR improves
      survival compared with no intervention in patients unfit for open repair of
      aortic aneurysm. METHODS: We did a randomised controlled trial of 338 patients
      aged 60 years or older who had aneurysms of at least 5.5 cm in diameter and who
      had been referred to one of 31 hospitals in the UK. We assigned patients to
      receive either EVAR (n=166) or no intervention (n=172). Our primary endpoint was
      all-cause mortality, with secondary endpoints of aneurysm-related mortality,
      health-related quality of life (HRQL), postoperative complications, and hospital
      costs. Analyses were by intention to treat. FINDINGS: 197 patients underwent
      aneurysm repair (47 assigned no intervention) and 80% of patients adhered to
      protocol. The 30-day operative mortality in the EVAR group was 9% (13 of 150, 95%
      CI 5-15) and the no intervention group had a rupture rate of 9.0 per 100 person
      years (95% CI 6.0-13.5). By end of follow up 142 patients had died, 42 of
      aneurysm-related factors; overall mortality after 4 years was 64%. There was no
      significant difference between the EVAR group and the no intervention group for
      all-cause mortality (hazard ratio 1.21, 95% CI 0.87-1.69, p=0.25). There was no
      difference in aneurysm-related mortality. The mean hospital costs per patient
      over 4 years were UK pound sterling 13,632 in the EVAR group and pound sterling
      4983 in the no intervention group (mean difference pound sterling 8649, SE 1248),
      with no difference in HRQL scores. INTERPRETATION: EVAR had a considerable 30-day
      operative mortality in patients already unfit for open repair of their aneurysm.
      EVAR did not improve survival over no intervention and was associated with a need
      for continued surveillance and reinterventions, at substantially increased cost.
      Ongoing follow-up and improved fitness of these patients is a priority.

PMID- 15978927
TI  - Can the world afford to save the lives of 6 million children each year?
AB  - BACKGROUND: In July, 2003, the Bellagio Study Group on Child Survival estimated
      that the lives of 6 million children could be saved each year if 23 proven
      interventions were universally available in the 42 countries responsible for 90%
      of child deaths in 2000. Here we assess the cost of delivering these
      interventions, and discuss whether the achievement of the Millennium Development
      Goal (MDG) for child survival falls within the financial capacities of donors and
      developing countries. METHODS: All child survival interventions shown to reduce
      mortality from the major causes of death in children younger than 5 years were
      incorporated into a delivery timetable comprised of 18 contacts between a child
      or mother and a health-care provider in the period from before birth until the
      child reaches 5 years. The running costs of delivering the interventions at
      universal coverage levels were calculated as the sum of unit costs for drugs and
      materials, delivery costs, and programme management and support costs, including
      supervision. We estimated the cost of providing interventions at coverage levels
      reported for 2000 and the additional costs of providing services at universal
      coverage levels. FINDINGS: USD 5.1 billion in new resources is needed annually to
      save 6 million child lives in the 42 countries responsible for 90% of child
      deaths in 2000. This cost represents 1.23 dollars per head in these countries, or
      an average cost per child life saved of 887 dollars. Sensitivity analyses for
      salary levels for community delivery agents, drug costs, and coverage rates for
      2000 were used to develop uncertainty estimates around the USD 5.1 billion annual
      price tag that range from about 3.1 billion dollars to 8.0 billion dollars.
      INTERPRETATION: Achieving the MDG for child survival is affordable for donors and
      developing countries. Scaling up health delivery is the challenge, and, along
      with the lack of funds, will be the limiting factor in reducing child mortality
      by two-thirds by 2015.

PMID- 15978928
TI  - Paternal depression in the postnatal period and child development: a prospective
      population study.
AB  - BACKGROUND: Depression is common and frequently affects mothers and fathers of
      young children. Postnatal depression in mothers affects the quality of maternal
      care, and can lead to disturbances in their children's social, behavioural,
      cognitive, and physical development. However, the effect of depression in fathers
      during the early years of a child's life has received little attention. METHODS:
      As part of a large, population-based study of childhood, we assessed the presence
      of depressive symptoms in mothers (n=13,351) and fathers (n=12,884) 8 weeks after
      the birth of their child with the Edinburgh postnatal depression scale (EPDS).
      Fathers were reassessed at 21 months. We identified any subsequent development of
      behavioural and emotional problems in their children (n=10,024) at age 3.5 years
      with maternal reports on the Rutter revised preschool scales. FINDINGS:
      Information was available for 8431 fathers, 11,833 mothers, and 10,024 children.
      Depression in fathers during the postnatal period was associated with adverse
      emotional and behavioural outcomes in children aged 3.5 years (adjusted odds
      ratio 2.09, 95% CI 1.42-3.08), and an increased risk of conduct problems in boys
      (2.66, 1.67-4.25). These effects remained even after controlling for maternal
      postnatal depression and later paternal depression. INTERPRETATION: Our findings
      indicate that paternal depression has a specific and persisting detrimental
      effect on their children's early behavioural and emotional development.

PMID- 15978929
TI  - Incidence, 30-day case-fatality rate, and prognosis of stroke in Iquique, Chile:
      a 2-year community-based prospective study (PISCIS project).
AB  - BACKGROUND: The epidemiology of stroke in Latin-American populations and
      variation of subtypes between communities are unclear. Our aim was to ascertain
      prospectively the incidence of first-ever stroke in the predominantly Hispanic
      Mestizo population of Iquique, a city in the northern desert region of Chile.
      METHODS: We prospectively identified all possible cases of stroke and transient
      ischaemic attacks between July 1, 2000, and June 30, 2002, from several
      overlapping sources. Patients were rapidly assessed by two field neurologists.
      Standard definitions for incident cases, stroke, transient ischaemic attack,
      pathological type, and infarction subtype were used. All cases identified were
      adjudicated by at least two stroke neurologists and followed up at 6 months.
      Incidence rates of first-ever strokes were calculated from the population of
      Iquique (214 526) according to the national census of 2002. FINDINGS: Of 380
      cases of stroke identified, 292 were incident. CT scans were done in 267 (91%)
      patients and the mean time to scan was 2.2 days. The hospital admission rate was
      71% (207/292). The overall age-adjusted incidence rate of first-ever stroke was
      140.1 per 100,000 (95% CI 124.0-156.2). The incidence rates per 100,000 according
      to pathological type were: infarcts 87.3, intracerebral haemorrhage 27.6, and
      subarachnoid haemorrhage 6.2. The 30 day and 6-month case-fatality rates were
      23.3% and 33.0%, respectively. INTERPRETATION: Our results show incidence rates
      of stroke similar to those reported in other community studies. Although the
      proportion of intracerebral haemorrhages was higher than reported in previous
      studies, the overall incidence was not, which could indicate a slightly lower
      incidence of ischaemic strokes in this population than in other countries. The
      prognosis was similar to that found in other population-based studies.

PMID- 15978930
TI  - Association with HLA class I in Epstein-Barr-virus-positive and with HLA class
      III in Epstein-Barr-virus-negative Hodgkin's lymphoma.
AB  - BACKGROUND: Associations of Hodgkin's lymphoma with HLA have been reported for
      many years. In 20-40% of patients with this disorder, Epstein-Barr virus (EBV) is
      present in the neoplastic cells. Because presentation of EBV antigenic peptides
      can elicit vigorous immune responses, we investigated associations of the HLA
      region with EBV-positive and EBV-negative Hodgkin's lymphoma. METHODS: In a
      retrospective, population-based study, patients with Hodgkin's lymphoma were
      reclassified according to the WHO classification, and EBV status was assessed by
      in-situ hybridisation of EBV-encoded small RNAs. Germline DNA was isolated from
      200 patients diagnosed between 1987 and 2000 and from their first-degree
      relatives. Genotyping was done with 33 microsatellite markers spanning the entire
      HLA region and two single-nucleotide polymorphisms in the genes for tumour
      necrosis factor alpha and beta. Classic association analysis and the haplotype
      sharing statistic were used to compare patients with controls. FINDINGS: Classic
      association analysis (but not the haplotype sharing statistic) showed an
      association of consecutive markers D6S265 and D6S510 (p=0.0002 and 0.0003),
      located in the HLA class I region, with EBV-positive lymphomas. The haplotype
      sharing statistic (but not classic association analysis) showed a significant
      difference in mean haplotype sharing between patients and controls surrounding
      marker D6S273 (p=0.00003), located in HLA class III. INTERPRETATION: Areas within
      the HLA class I and class III regions are associated with susceptibility to
      Hodgkin's lymphoma, the association with class I being specific for EBV-positive
      disease. This finding strongly suggests that antigenic presentation of EBV
      derived peptides is involved in the pathogenesis of EBV-involved Hodgkin's
      lymphoma. RELEVANCE TO PRACTICE: Polymorphisms in the HLA region could explain
      ethnic variation in the incidence of Hodgkin's lymphoma. The association of EBV
      positive Hodgkin's lymphoma with HLA class I suggests that this polymorphism
      might affect the proper presentation of EBV antigens to cytotoxic T lymphocytes.

PMID- 15978931
TI  - Alpha1-antitrypsin deficiency.
AB  - Alpha1-antitrypsin deficiency is a genetic disorder that affects about one in
      2000-5000 individuals. It is clinically characterised by liver disease and early
      onset emphysema. Although alpha1 antitrypsin is mainly produced in the liver, its
      main function is to protect the lung against proteolytic damage from neutrophil
      elastase. The most frequent mutation that causes severe alpha1-antitrypsin
      deficiency arises in the SERPINA 1 gene and gives rise to the Z allele. This
      mutation reduces concentrations in serum of alpha1 antitrypsin by retaining
      polymerised molecules within hepatocytes: an amount below the serum protective
      threshold of 11 micromol/L increases risk for emphysema. In addition to the usual
      treatments for emphysema, infusion of purified alpha1 antitrypsin from pooled
      human plasma represents a specific treatment and raises the concentrations in
      serum and epithelial-lining fluid above the protective threshold. Evidence
      suggests that this approach is safe, slows the decline of lung function, could
      reduce infection rates, and might enhance survival. However, uncertainty about
      the cost-effectiveness of this expensive treatment remains.

PMID- 15978932
TI  - Calcimimetics and calcilytics--fooling the calcium receptor.
AB  - CONTEXT: Just a decade after the the calcium-sensing receptor (CaR) was
      identified, pharmacological manipulation of the CaR is about to enter routine
      practice. For hyperparathyroid states, calcimimetics, which increase activation
      of the CaR, have been licensed in Europe and the USA. Calcilytics, which decrease
      CaR function and increase secretion of parathyroid hormone (PTH), might allow the
      anabolic effects of PTH on bone to be harnessed for the prevention and treatment
      of osteoporosis. STARTING POINT: In a multicentre randomised double-blind placebo
      controlled study, Munro Peacock and colleagues recently confirmed the efficacy of
      the oral calcimimetic cinacalcet for achieving long-term reductions in serum
      calcium and PTH concentrations in primary hyperparathyroidism (J Clin Endocrinol
      Metab 2005; 90: 135-41). The arrival of a non-surgical option for this common
      disorder is important. WHAT NEXT? Study in primary and uraemic secondary
      hyperparathyroidism will indicate whether the efficacy of calcimimetic agents
      extends into the longer term. The extracellular relation between the CaR and its
      ligands and the intracellular signalling cascades that modify PTH gene
      transcription and secretion need further study. Drugs acting on the CaR might
      treat other disorders of bone remodelling, including osteoporosis. CaR expression
      in tissues beyond those involved in mineral ion homoeostasis should remain an
      important focus of research.

PMID- 15978933
TI  - Guiltless resignation.

PMID- 15978934
TI  - Tension pneumothoraces.

PMID- 15978935
TI  - Blinded by pressure and pain.

PMID- 15978937
TI  - Signal transduction of phorbol 12-myristate 13-acetate (PMA)-induced growth
      inhibition of human monocytic leukemia THP-1 cells is reactive oxygen dependent.
AB  - Human monocytic THP-1 cells can be induced to differentiate to macrophages when
      treated with phorbol 12-myristate 13-acetate (PMA). It is understood that before
      initiating cell differentiation, PMA treatment must first induce an inhibition of
      cell growth. Since the initial biochemical and molecular events that are
      associated with this growth inhibition have not been characterized, the present
      study was carried out to elucidate the molecular mechanisms associated with the
      PMA-induced growth arrest of THP-1 cells. Our results indicate that PMA inhibits
      THP-1 cells at G1-phase of the cell cycle, via a complex mechanism associated
      with the modulation of the expression of several cell cycle regulators, initiated
      by the cellular generation of reactive oxygen species (ROS). Both p21WAF1/CIP1
      mRNA and protein were upregulated 24 h post PMA treatment as demonstrated by
      ribonuclease protection assay and Western blotting, respectively. Because these
      cells lack functional p53, this effect was independent of p53 activity.
      Electrophoretic mobility shift assay showed that the PMA-induced activation of
      the p21WAF1/CIP1 promoter was driven by the specific protein 1 (Sp1)
      transcription factor through Sp1-binding sites. Additionally, our study
      demonstrates that PMA-induces the upregulation of p21 through a protein kinase C
      (PKC)-mediated ROS-dependent signaling mechanism involving MAP kinase activation.

PMID- 15978938
TI  - Aberrant DNA methylation of a cell cycle regulatory pathway composed of P73, P15
      and P57KIP2 is a rare event in children with acute lymphocytic leukemia.
AB  - Aberrant DNA methylation of multiple promoter associated CpG islands is a
      frequent phenomenon in acute lymphocytic leukemia (ALL). Recently, methylation of
      a cell cycle control pathway composed of P73, P15 and P57KIP2 has been shown to
      confer poor prognosis to adult patients with ALL. Using bisulfite PCR methods, we
      have explored the prevalence of methylation of this pathway in a cohort of
      children with ALL (N=20), and compared these results with those observed in a
      group of adult patients (N=53). P73 was methylated in 4 (20%) pediatric patients,
      P15 in 3 (15%), and P57KIP2 in 2 (10%). These compared to 14 (26%), p=0.5, 16
      (30%), p=0.04 and 20 (37%), p=0.04, respectively in adult patients. Methylation
      of two or more genes was not observed in any pediatric patient, but in 15 (28%)
      adult patients (p=0.003). Poor survival of adult patients was associated with
      methylation of > or =2 genes (p=0.003). These results indicate that differences
      in DNA methylation of specific molecular pathways may contribute to the
      prognostic differences known to occur between pediatric and adult patients with
      ALL.

PMID- 15978939
TI  - Induction of apoptosis in K562 human leukemia cells by 2',4'-dihydroxy-6'-methoxy
      3',5'-dimethylchalcone.
AB  - 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), isolated from the buds
      of Cleistocalyx operculatus, was investigated in its cytotoxicity and anti
      proliferation on K562 cell line. Our results revealed that the IC50 was equal to
      14.2+/-0.45 microM and the EC50 was 3.3+/-0.14 microM. Staining with Hoechst
      33258 showed fragmentation and condensation of chromatin in the cells treated
      with 8 microM DMC for 48 h. Flow cytometric analysis was performed to determine
      hypodiploid cells. The results of flow cytometry assay indicated that the
      percentage of hypodiploid K562 cells was 76.15+/-3.22% after 48 h treatment with
      16.0 microM DMC. The treatment resulted in the appearance of a hypodiploid peak
      (A0 region), probably due to the presence of apoptosing cells and/or apoptotic
      bodies with DNA content less than 2n. Western blot results illustrated that in
      the same dosage and incubation time, DMC could down-regulate the level of Bcl-2
      protein and did not influence the expression of Bax protein. The resulting net
      effect could thus lead to a lower ratio of Bcl-2/Bax, which might be responsible
      for the DMC-induced apoptosis in K562 cells.

PMID- 15978940
TI  - Over-expression of Flt3 induces NF-kappaB pathway and increases the expression of
      IL-6.
AB  - Activating mutations or over-expression of the Flt3 is prevalent in acute
      myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and
      other signaling pathways. In this study, we addressed the role of Flt3 in the
      activation of nuclear factor-kappa B (NF-kappaB), which is a target molecule of
      these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-kappaB
      responsive reporter was upregulated and its target gene, IL-6, was increased by
      the involvement of Flt3-ERK/MAPK-NF-kappaB pathway. Furthermore, we found a
      modest positive correlation (r=0.35, p=0.096) between Flt3 and IL-6 mRNA
      expression in 24 AML specimens. These results suggest a role of Flt3 over
      expression in NF-kappaB pathway.

PMID- 15978941
TI  - Nuclear topography and expression of the BCR/ABL fusion gene and its protein
      level influenced by cell differentiation and RNA interference.
AB  - Nuclear topography, expression of the BCR/ABL fusion gene and its protein
      level/cellular pattern were studied in CML cell line K562 stimulated to
      differentiation, apoptosis and influenced by ABL-RNA interference (ABL-RNAi).
      Phorbol ester-induced maturation of K562 cells was accompanied by repositioning
      of down-regulated BCR/ABL genes closer to the nuclear membrane. This nuclear
      rearrangement could be connected with differentiation-related
      heterochromatinization of the amplified BCR-ABL locus, as demonstrated by
      increased histone H3(K9) dimethylation and decreased H3(K9) acetylation of B3A2
      breakpoint. Topography of BCR/ABL in differentiated K562 cells was compared with
      other leukemic cell types: PMA-maturation of HL60 cells did not influence the
      nuclear positioning of individual BCR and ABL genes. Moreover, BCR and ABL genes
      in non-stimulated HL60 as well as in the bone marrow cells of CML patients, i.e.
      also BCR/ABL fusion genes, were positioned more interiorly in comparison with
      BCR/ABL multiple loci of K562 cells. Decreased expression of BCR/ABL gene was
      also found after cell stimulation by selectively pro-apoptotic agent etoposide
      and by ABL-RNAi leading to apoptosis. In order to compare the efficiency of
      selected experimental strategies, levels of Bcr/Abl and c-Abl proteins were
      determined and in all cases tested were reduced. In K562 cells the Bcr/Abl and c
      Abl proteins were distributed homogeneously in both the cell nucleus and
      cytoplasm, while differentiation of K562 cells was characterized by a distinct
      pattern of Bcr/Abl and c-Abl proteins that were focally distributed rather in the
      cytoplasm while apoptotic population was completely absent of Bcr/Abl and c-Abl
      signals.

PMID- 15978942
TI  - Targeting cannabinoid receptors to treat leukemia: role of cross-talk between
      extrinsic and intrinsic pathways in Delta9-tetrahydrocannabinol (THC)-induced
      apoptosis of Jurkat cells.
AB  - Targeting cannabinoid receptors has recently been shown to trigger apoptosis and
      offers a novel treatment modality against malignancies of the immune system.
      However, the precise mechanism of apoptosis in such cancers has not been
      previously addressed. In this study, we used human Jurkat leukemia cell lines
      with defects in intrinsic and extrinsic signaling pathways to elucidate the
      mechanism of apoptosis induced by Delta9-tetrahydrocannabinol (THC). We observed
      that Jurkat cells deficient in FADD or caspase-8 were partially resistant to
      apoptosis, while dominant-negative caspase-9 mutant cells were completely
      resistant to apoptosis. Use of caspase inhibitors confirmed these results.
      Furthermore, overexpression of Bcl-2 rendered the cells resistant to THC at early
      time points but not upon prolonged exposure. THC treatment led to loss of
      Deltapsi(m), in both wild-type and FADD-deficient Jurkat cells thereby suggesting
      that THC-induced intrinsic pathway was independent of FADD. THC treatment of wild
      type Jurkat cells caused cytochrome c release, and cleavage of caspase-8, -9, -2,
      -10, and Bid. Caspase-2 inhibitor blocked THC-induced caspase-3 in wild-type
      Jurkat cells but not loss of Deltapsi(m). Together, these data suggest that the
      intrinsic pathway plays a more critical role in THC-induced apoptosis while the
      extrinsic pathway may facilitate apoptosis via cross-talk with the intrinsic
      pathway.

PMID- 15978943
TI  - JAK-STAT signaling involved in phorbol 12-myristate 13-acetate- and dimethyl
      sulfoxide-induced 2'-5' oligoadenylate synthetase expression in human HL-60
      leukemia cells.
AB  - The JAK-STAT signal transduction cascade participates in various cellular
      processes, including immune response, cell replication, differentiation and
      oncogenesis. Here, we report that this cascade is induced in two human myeloid HL
      60 leukemia cell variants by the granulocyte differentiation inducer dimethyl
      sulfoxide (DMSO) and macrophage differentiation inducer phorbol 12-myristate 13
      acetate (PMA). DMSO and PMA also induced the expression and catalytic activity of
      2'-5' oligoadenylate synthetase (2-5A synthetase), a known interferon (IFN)
      inducible enzyme. The HL-60 cell variants included HL-205, which is susceptible
      to DMSO- and PMA-induced differentiation, and HL-525, which is susceptible to
      DMSO- but not to PMA-induced differentiation. Treatment of HL-205 and HL-525
      cells with DMSO and HL-205 cells with PMA-induced JAK1 phosphorylation,
      JAK1/STAT1 association, formation of STAT1-STAT2 heterodimers, and the binding of
      the active IFN stimulating growth factor 3 (ISGF3) to the IFN-stimulated response
      element (ISRE) fragment isolated from the 2-5A synthetase promoter. These events
      were either reduced or absent in the resistant HL-525 cells treated with PMA.
      Taken together, our data implicate the above signaling cascade in DMSO- and PMA
      induced 2-5A synthetase expression and catalytic activity in the HL-60 cell
      system.

PMID- 15978944
TI  - Resistance against Friend leukemia virus-induced leukemogenesis in DNA-dependent
      protein kinase (DNA-PK)-deficient scid mice associated with defective viral
      integration at the Spi-1 and Fli-1 site.
AB  - Retroviral DNA integration is mediated by the viral protein integrase. However,
      elements of the host DNA repair machinery such as the phosphatidylinositol 3
      kinase (PI-3K)-related protein kinase family system would play a role in the
      integration of viral DNA into the host DNA. Here, we show that a host PI-3K
      related protein kinase, DNA-dependent protein kinase (DNA-PK), plays a role in
      the specific integration of retroviral DNA and induction of retroviral diseases
      in vivo. DNA-PK-deficient scid mice inoculated with Friend leukemia virus (FLV)
      exhibited a random integration into their genomic DNA and expressed the viral
      envelope protein gp70. However, the specific integration of FLV at Spi-1 or Fli-1
      sites did not occur in association with the significant resistance of scid mice
      to FLV-induced leukemogenesis. In contrast, the knockout of another member of the
      PI-3K-related protein kinase family, encoded by the ataxia telangiectasia mutated
      (ATM) gene, resulted in mice as sensitive to FLV-induced leukemogenesis as the
      wild type mice. FLV was specifically integrated into the DNA at Spi-1 and Fli-1
      sites with significant expression of these transcription factors. These findings
      indicated that DNA-PK would be essential for controlling the in vivo integration
      of FLV at specific sites as well as the susceptibility to FLV-induced
      leukemogenesis.

PMID- 15978945
TI  - Retroviral expression screening of oncogenes in natural killer cell leukemia.
AB  - Aggressive natural killer cell leukemia (ANKL) is an intractable malignancy that
      is characterized by the outgrowth of NK cells. To identify transforming genes in
      ANKL, we constructed a retroviral cDNA expression library from an ANKL cell line
      KHYG-1. Infection of 3T3 cells with recombinant retroviruses yielded 33
      transformed foci. Nucleotide sequencing of the DNA inserts recovered from these
      foci revealed that 31 of them encoded KRAS2 with a glycine-to-alanine mutation at
      codon 12. Mutation-specific PCR analysis indicated that the KRAS mutation was
      present only in KHYG-1 cells, not in another ANKL cell line or in clinical
      specimens (n=8).

PMID- 15978946
TI  - Suppressive effect of human herpesvirus-8/Kaposi sarcoma-associated herpesvirus
      on in vitro colony formation of hematopoietic progenitor cells.

PMID- 15978947
TI  - Uptake of high density lipoprotein (HDL) cholesteryl esters by human acute
      leukemia cells.
AB  - Hypocholesterolemia is a common finding in patients with acute leukemia (AL). The
      aim of this study is to investigate if blast myeloid and lynfoid cells take up
      more high density lipoprotein (HDL) cholesteryl esters than normal cells of the
      same origin. The HDL-cholesteryl ester uptake followed a kinetic saturation
      process. Higher maximal velocity rates were found in lymphoblasts and myeloblasts
      compared to normal cells (Vmax=3.51+/-0.30/3.61+/-0.16 and 2.54+/-0.12/2.28+/
      0.12 microg/mg, respectively). High density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C) and total cholesterol were significantly
      lower in AL patients (p<0.05); no differences were observed in triglyceride or
      VLDL-C levels. In conclusion, low HDL-C levels observed in AL may be related to
      an overexpression of a selective HDL-cholesteryl ester putative site.

PMID- 15978948
TI  - Prognostic role of minimal residual disease in multiple myeloma patients after
      non-myeloablative allogeneic transplantation.
AB  - This study evaluates the prognostic value of molecular monitoring of minimal
      residual disease (MRD) in 20 patients with multiple myeloma (MM) following
      autologous (peripheral blood stem cell transplantation, PBSCT) and non
      myeloablative allogeneic (NMT) transplant. All patients completed their program,
      with a treatment-related mortality (TRM) of 20% and a 2-year progression-free
      survival (PFS) of 51%. After PBSCT, only 3 patients (15%) achieved PCR
      negativity, versus 12 (60%) after NMT. The eradication of MRD had a favorable
      impact on 2-year OS. In fact, 76% of patients with no detectable MRD was still
      alive versus 34% of persistently IgH-positive cases (p=0.03). PCR status did not
      correlate with chimerism percentage: Seventy-five percent of patients achieved
      full donor chimerism, which was more frequently observed in cases presenting
      cGHVD (p=0.01). These data sustain the relevant role of molecular monitoring in
      MM patients undergoing NMT. MRD monitoring would assist physicians in making
      additional therapeutic decisions to better control this hematological malignancy.

PMID- 15978949
TI  - Hairy cell leukemia (HCL) with extensive myelofibrosis responds to thalidomide.
AB  - We present a 75-year-old man who was admitted to our hospital because of
      splenomegaly, transfusion-dependent anemia and thrombocytopenia. The diagnosis of
      idiopathic myelofibrosis was suggested by the bone marrow trephine biopsy, which
      was hypocellular with myelofibrosis. Thalidomide was started at a daily dose of
      100 mg/d and increased to 400 mg/d. Within 12 weeks, thrombocytes increased to
      100.000/microl, hemoglobin normalized, lasting for about 11 months. Then,
      thalidomide had to be discontinued because of mild polyneuropathy. A second bone
      marrow biopsy showed fibrosis as well as a diffuse infiltration of the bone
      marrow (80%) by lymphocytes with expression of CD11c, CD19, CD20, CD103. Tartrate
      resistant acid phosphatase test (TRAP) was also positive. Hairy cell leukemia was
      diagnosed and he was administered 2-chlorodeoxyadenosine (2-CDA) achieving a
      complete remission.

PMID- 15978950
TI  - Pregnancy under treatment of imatinib and successful labor in a patient with
      chronic myelogenous leukemia (CML). Outcome of discontinuation of imatinib
      therapy after achieving a molecular remission.
AB  - Because of the teratogenicity data in rats, it is recommended that women treated
      with imatinib should be aware of the potential teratogenicity of imatinib and
      effective contraception should be used during imatinib therapy to prevent
      pregnancy. We describe successful pregnancy and delivery, without any congenital
      anomaly, in a patient with CML under treatment of imatinib. The fetus had been
      exposed to imatinib for 8 weeks. The patient remained off treatment during
      gestation and cytogenetic relapse of CML (5 months after discontinuation of
      imatinib therapy) developed at seventh month of gestation.

PMID- 15978952
TI  - CD5 negative and CD5 positive splenic marginal B-cell lymphomas have differential
      cytogenetic patterns.

PMID- 15978951
TI  - Idiopathic hypereosinophilic syndrome: a case evolving in B-lymphoblastic
      lymphoma.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a rare disease characterized by
      tissue involvement and organ dysfunction due to abnormal eosinophil
      proliferation. Evolution of HES into myeloid or T-cell malignancies has been
      frequently reported. Here, we describe a case of HES that preceded the occurrence
      of a high-grade B-lymphoblastic lymphoma in which clonal evolution has been
      demonstrated at the molecular level.

PMID- 15978953
TI  - Mapping the binding site for gossypol-like inhibitors of Plasmodium falciparum
      lactate dehydrogenase.
AB  - Gossypol is a di-sesquiterpene natural-product in the form of a functionalised
      binaphthyl and is isolated from cotton plants. The compound has long been known
      to exhibit anti-malarial and other biological activities. Previous studies have
      indicated that compounds of this type target Plasmodium falciparum lactate
      dehydrogenase (pfLDH), an essential enzyme for energy generation within the
      parasite. In this study, we report that simple naphthalene-based compounds, the
      core of the gossypol structure, exhibit weak inhibition of the parasite lactate
      dehydrogenase. Crystal structures of the complexes formed by binding of these
      naphthalene-based compounds to their target enzyme have been used to delineate
      the molecular features likely to form the gossypol binding site. Two modes of
      binding are observed: one overlapping the pyruvate but not the co-factor site,
      the other bridging the binding sites for the co-factor nicontinamide group and
      pyruvate substrate. This latter site encompasses molecular features unique to
      Plasmodium forms of LDH and is likely to represent the mode of binding for
      gossypol derivatives that show selectivity for the parasite enzymes. We also
      report a substrate analogue that unexpectedly binds within the adenine pocket of
      the co-factor groove. Although these core pharmacophore-like molecules only
      exhibit low levels of inhibitory activity, these molecular snapshots provide a
      rational basis for renewed structure-based development of naphthalene-based
      compounds as anti-malarial agents.

PMID- 15978954
TI  - Amino acid sequence constraint and gene expression pattern across the life
      history in the malaria parasite Plasmodium falciparum.
AB  - The relationship between gene expression across the life cycle and protein
      conservation in Plasmodium falciparum was examined by comparing gene expression
      data for six life-history stages with the number of nonsynonymous substitutions
      per site dN between 901 orthologous gene pairs of P. falciparum and Plasmodium
      yoelii. A high level of expression across the life history was associated with
      decreased dN and thus with protein conservation. By contrast, differential
      expression in the sporozoite and merozoite stages was associated with increased
      dN. At least some sporozoite- and merozoite-expressed genes with high dN have
      probably been subject to positive selection arising from parasite-host
      coevolution. A high level of expression across the life history was associated
      with higher than average G+C content at the first and second codon positions,
      whereas a high level of expression in the sporozoite and merozoite was associated
      with reduced G+C content at the first and second codon positions, the latter
      pattern evidently reflecting the relaxation of constraint on the amino acid
      sequence.

PMID- 15978955
TI  - Adhesion of Plasmodium falciparum-infected red blood cells to CD36 under flow is
      enhanced by the cerebral malaria-protective trait South-East Asian ovalocytosis.

PMID- 15978956
TI  - Health systems factors influencing maternal health services: a four-country
      comparison.
AB  - It is widely understood that maternal health care relies on the entire health
      system. However, little empirical, country-specific, research has been done to
      trace out the ways in which health system elements can shape maternal health
      outcomes. This study seeks to redress this situation, by providing an example of
      how a health systems approach can benefit the understanding of maternal health
      services. A comparative analysis was conducted based on extensive case studies of
      maternal health and health systems in Bangladesh, Russia, South Africa, and
      Uganda. A number of cross-cutting health system characteristics affecting
      maternal health were identified by comparing these diverse settings. The most
      important common systems issues underlying maternal health care were found to be
      the human resource structures, the public-private mix of service provision, and
      the changes involved with health sector reforms. Specific country contexts can
      further determine many factors influencing maternal health outcomes and service
      performance. Systems issues were found to influence the access to and utilization
      of services, quality of care provided, and ultimately maternal health outcomes.
      This paper provides a first step in tracing out how such broad systems issues
      actually work to influence maternal health.

PMID- 15978957
TI  - Evaluating the health benefits and cost-effectiveness of the radon remediation
      programme in domestic properties in Northamptonshire, UK.
AB  - Although previous analysis of health benefits and cost-effectiveness of radon
      remediation in a series of houses in Northamptonshire suggested that testing and
      remediation was justified, recent results indicate fewer predicted affected
      houses than previously assumed. Despite numerous awareness campaigns, limited
      numbers of householders have tested their homes, only a minority of affected
      householders have remediated, and those most at risk generally fail to remediate.
      Moreover, a recent survey shows a wide range of public perception of radon risk,
      not significantly influenced by public health campaigns. These observations
      impact our previous analysis, which has been reviewed in the light of these
      observations. Following the declaration of Northamptonshire, UK, as a radon
      Affected Area in 1992, a series of public awareness campaigns encouraged
      householders to assess domestic radon levels and, if appropriate, to take action
      to reduce them. Despite these awareness campaigns, however, only moderate numbers
      of householders have taken remediatory action. The costs of such remedial work in
      a series of domestic properties in Northamptonshire, the radon level reduction
      achieved, and the resultant heath benefit to the residents, have been the subject
      of study by our group for some years. Previous analysis, based on estimates of
      the total number of affected houses derived from the National Radiological
      Protection Board (NRPB) test data for the area, suggested that a programme of
      testing and remediation in Northamptonshire could be justified. The NRPB has
      continued to initiate and to collate radon testing, and published further results
      in 2003. These results include revised predictions of the numbers of affected
      houses, now considered to be less than the numbers previously assumed. More
      recently, the availability of the European Community Radon Software (ECRS) has
      permitted calculation of individual, rather than population-average, risk,
      demonstrating that those most at risk are generally those who do not take action.
      In addition, a recent survey of risk perception shows an extremely wide range of
      public perception of radon risk, a perception that has not been significantly
      altered by public health campaigns. These predictions have profound effects, both
      on our previous analysis, particularly since only limited numbers of householders
      test their homes and even fewer remediate if they discover raised levels, and
      also on the public health strategies for this risk.

PMID- 15978958
TI  - Partnership for the heart. German-Estonian health project for the treatment of
      congenital heart defects in Estonia.
AB  - Congenital heart defects (CHD) occur in 8 per 1000 live births. If they remain
      untreated, 70-80% of these patients die in early childhood. With modern
      diagnostic and treatment procedures, 90% of these patients reach adulthood.
      Within 8 years following reunification of Germany, it was possible to improve
      treatment for CHD in former East Germany to West German standards. Based on the
      experience gained in this process, a plan for improvement of care of Estonian
      patients with CHD was developed and implemented in the German-Estonian project,
      "Partnership for the Heart". The main elements of the project were (1) the
      training of Estonian physicians in Germany, (2) training courses conducted by
      German and Estonian specialists in Estonia and (3) use of telemedicine for
      consultation on a continuous basis. During the project 15 Estonian patients
      underwent cardiac surgery and/or catheter interventions performed by a joint team
      of German and Estonian specialists. The infant mortality due to CHD in Estonia
      fell by 28% during the project period. Key techniques of cardiac surgery are now
      being employed in Estonia without outside support, indicating the success of the
      training program and the long-term improvements to cardiac health care in
      Estonia. The total project costs were 314,252 Euro (euro), which is 50% lower
      than the estimated cost of treating the 15 patients abroad in Western Europe. The
      structure of "Partnership for the Heart" and the modified self-sufficiency model
      of medical care have not only produced results for Estonia but can be taken as a
      template for future bilateral health projects with other transition countries and
      for other fields of medical specialisation, and thus might aid a European health
      policy.

PMID- 15978959
TI  - Payment mechanisms and prescriptions in four Thai hospitals.
AB  - This paper examines the effect of payment mechanisms on prescription patterns in
      four district hospitals in provincial Thailand. Outpatients aged 60 or over at
      the four hospitals belong either to an insurance scheme that funds hospitals on a
      fee-for-service basis, or to a scheme using capitation. Hospitals have a
      financial incentive to differentiate between patients belonging to different
      schemes; however, doctors, who are paid salaries, face different pressures. The
      paper has two objectives: (i) to describe financial and non-financial influences
      on doctors' prescribing decisions; (ii) to test for differences between the cost
      of prescriptions received by fee-for-service and those received by capitated
      patients. The analysis uses data from treatment records, surveys, and interviews.
      We find that prescription costs for fee-for-service patients are significantly
      higher than those for capitated patients, controlling for age, sex, diagnosis and
      (to a limited extent) socio-economic status. The cost differences are
      attributable entirely to differences in the probability of receiving expensive
      drugs, and owe nothing to differences in quantities prescribed.

PMID- 15978960
TI  - Caring externalities in health economic evaluation: how are they related to
      severity of illness?
AB  - In health economic evaluations, altruistic preferences in the form of caring
      externalities, i.e. that people care about others' health, is usually not taken
      into account. In this study we examined how people value their own and others'
      health. This pilot study was carried out by letting people answer willingness to
      pay (WTP) questionnaires where internal WTP (own health) and altruistic WTP
      (others' health) were isolated and examined. A common method used in health
      economic evaluations is cost-utility analysis, which is based on the maximisation
      of QALYs. QALY maximisation may be appropriate if altruistic preferences are non
      existent or if they are linear in relation to internal preferences (QALYs
      gained). We found evidence for the existence of altruistic preferences and that
      these preferences were relatively higher for severe health states (and lower for
      mild states of health) compared to internal preferences, i.e. when severity of
      illness increased, the relative increase in caring was higher concerning others
      than oneself. The difference was statistically significant (P<0.001). Our results
      indicate that more attention and resources should be directed to severe health
      states, as compared to mild health states, than advocated by internal preferences
      in order to obtain more efficient resource allocation in the health care sector.

PMID- 15978961
TI  - Health care resource allocation and individuals' health care needs: examining the
      degree of fit.
AB  - Previous studies examine associations between health system resources and an
      individual's use of health services, yet the importance of these resources in
      meeting an individual's health care needs is unclear. This paper examines the
      relationship between health care system characteristics, other social and
      economic characteristics of counties in a mid-western U.S. state and an
      individual's ability to meet health care needs over a 12-month period. We
      conclude that policy interventions are needed that look beyond health resource
      allocation to address problems in health care access that contribute to
      inequities in health.

PMID- 15978962
TI  - Use of cervical cancer screening among insured women: the extent of missed
      opportunities.
AB  - The objective of the study is to identify opportunities to improve cervical
      cancer screening among privately insured women. From MedStat's Marketscan
      database, we identified 735,181 women aged 21-64 years who remained in the same
      insurance plan during the entire period of 2000-2002. We obtained the percentages
      of women who had a Papanicolaou (Pap)-test reimbursement claim and any health
      related claim during the 3-year period. For women without a Pap-test claim, we
      obtained information about the frequency of insurance claims, type of health-care
      provider, and type of insurance plan in which the women were enrolled. The
      multivariate logistic regression model was used to identify factors independently
      associated with not having a Pap test. Of the total sample, in the 3-year period,
      96% had at least one health insurance reimbursement claim and 69% had at least
      one claim for a Pap test. Approximately, 87% of the women who had no Pap-test
      claim had a health claim; 44% of such claims were from primary care providers. In
      the multiple logistic regression model, factors that were independently
      associated with having no Pap test were old age, being dependents of employees,
      and enrollment in comprehensive insurance plans. Efforts to increase the use of
      cervical cancer screening service should consider additional risk factors besides
      lack of insurance coverage. Concerted efforts by insurance and health-care
      providers are needed to improve adherence to the recommended cervical cancer
      screening guidelines, both by consumers and service providers.

PMID- 15978963
TI  - Hospital cost of ischemic stroke and intracerebral hemorrhage in Japanese stroke
      centers.
AB  - BACKGROUND: In Japan, the healthcare expenditure has increased to 8.0% of the
      gross domestic products in 2001. Stroke care is costly. OBJECTIVE: To examine
      hospital costs and clinical outcomes of ischemic stroke (IS) and intracerebral
      hemorrhage (ICH) in Japanese stroke centers. DESIGN: A prospective non
      interventional multi-center study. SETTING: Ten Japanese stroke centers. STUDY
      PERIOD: Fourteen months between October 2000 and December 2001. PATIENTS:
      Patients were those who were consecutively hospitalized with acute IS or ICH
      within 72 h of onset, excluding subarachnoid hemorrhage. Stroke was defined as
      focal neurological deficits lasting more than 24 h and the relevant lesions were
      to be confirmed by brain CT and/or MRI. METHODS: We examined demography, in
      hospital cares, length of hospital stay, clinical outcomes at discharge, and
      direct hospital medical costs including physician's fees. The hospital medical
      cost data were collected from official hospital medical cost charts for
      reimbursement to the healthcare insurance systems. RESULTS: There were a total of
      1113 patients with a mean age of 70 years, of whom 913 (82%) patients had an IS
      and 200 (18%) patients had an ICH. The 317 patients (28%) experienced a recurrent
      stroke. Patients with ICH had the higher baseline stroke severity, resulting in
      longer hospitalization (39 days for IS and 46 days for ICH; P<0.001), lower
      independence rate at discharge (55 and 40%; P<0.001), higher mortality rate (5
      and 10%; P=0.03), and higher medical costs (US dollar 8662 and US dollar 10,260;
      P<0.001) than those with IS. Patients with recurrent stroke had significantly
      older age, higher stroke severity, and lower independence rate at discharge than
      those with first-ever stroke. The length of stay, in-hospital mortality, and
      hospital medical costs were similar among first-ever and recurrent strokes. In
      subtype of IS, patients with cardioembolic stroke had the worst neurological
      deficits, poorest outcomes, and highest medical costs. The hospital costs had a
      greatest association with length of stay. CONCLUSIONS: Stroke care is costly in
      Japan. ICH is more likely to impose substantial physical and economic burden than
      IS. Because the cares of both first-ever and recurrent stroke were costly,
      primary and secondary prevention of stroke is important on the healthcare
      aspects.

PMID- 15978964
TI  - Decentralisation and TB control in Nepal: understanding the views of TB control
      staff.
AB  - Experience shows that planners need to consider the effect of the process of
      decentralisation on national health programmes. The aim of this article is to
      explore the relationship between decentralisation and a national disease control
      programme by seeking to understand the views and attitudes of staff working in a
      national TB control programme on the process of change and their involvement in
      that change. The study to which this paper refers was performed in Nepal, where,
      in common with several low- and middle-income countries, a Local Self Governance
      Act has been passed and decentralisation is in the process of being introduced in
      the health sector. The aim of the study was to develop a process of initial
      dialogue among programme staff with a view to exemplifying those enabling and
      disabling factors which could influence the process and content of health systems
      development and its impact on health and health care. The study used individual
      interviews and group discussions to increase our understanding of the experience
      of different stakeholders at both national and district levels. Important
      problems identified include: confused lines of authority, difficulties of
      integrated supervision, poor career paths and promotion possibilities, unclear
      performance management, lack of priority to be given to health and TB control,
      lack of local accountability, lack of capacity and the risk to the drug supply.
      The study highlights the need to (a) develop consensus techniques, achieve a
      balanced appreciation and include all stakeholders in the process of change and
      (b) define central and local responsibilities, limiting political bias,
      maintaining quality control, organising different lines of authority, maintaining
      priorities and programme integration.

PMID- 15978965
TI  - Evaluating daily nursing use and needs in the intensive care unit: a method to
      assess the rate and appropriateness of ICU resource use.
AB  - BACKGROUND: We designed a tool to measure the rate and appropriateness of
      intensive care unit (ICU) nursing coverage as a proxy for the use of resources.
      METHODS: We tested the tool in 32 Italian ICUs during a cross-sectional study (4
      days/week, October 2001 and April 2002). The level of care was classified as high
      or low. The appropriate patient-to-nurse ratio for both levels (2/1 and 3/1 in
      this ICU mix) was defined. The provided and theoretical nurse assistance was
      computed, the difference between the two quantifying the ICU use of personnel: a
      positive difference means over-utilization, a negative one under-utilization. We
      calculated the maximum number of high-level and low-level care days available for
      ICU and the relative utilization rates. These two rates quantify the
      appropriateness of resource use in relation to the planned use. RESULTS:
      Analysing 5783 treatment-days, the tool identified units using almost all
      available resources (five), overcrowded (14: too small units) or empty (16: too
      big). Units were overcrowded on account of the high-level of care required (five:
      utilization rate >100%) or reallocated too much of their residual high-care
      nursing capacity to low-level care (six). In empty units both utilization rates
      were lower than expected. CONCLUSIONS: The method quantifies the rate and
      appropriateness of resource usage and suggests the best management in units with
      fixed human resources or a fixed number of beds.

PMID- 15978966
TI  - Women's attitude and perceptions towards menopause in different cultures. Cross
      cultural and intra-cultural comparison of pre-menopausal and post-menopausal
      women in Germany and in Papua New Guinea.
AB  - OBJECTIVE: To study cross-cultural and intra-cultural differences between the
      perception and the experience of menopause in pre-menopausal and post-menopausal
      German and Papua New Guineas women. DESIGN: Concepts concerning menopause and the
      experience of the menopause were assessed by the symptom categories (i.e. hot
      flashes, cardiac or sleeping disorders, depression, irritability, lack of drive,
      vaginal dryness, painful joints or muscles) according to the Menopause Rating
      Scale (MRS). In addition to the translated English version, a questionnaire in
      Pidgin-English was offered. Questions about positive and negative expectations of
      menopause and the acceptance of hormonal replacement therapy were included.
      Statistical analysis was performed using Chi-square test and the Mann-Whitney U
      test as indicated. RESULTS: One hundred and one pre-menopausal and 40 post
      menopausal women in Germany as well as 36 pre-menopausal and 41 post-menopausal
      women in Papua New Guinea were questioned. The expectations regarding the
      menopause differed significantly in favor of a higher trait intensity concerning
      the item of hot flashes in Germany and a significantly higher trait intensity in
      the items cardiac trouble, lack of drive, urological symptoms, vaginal dryness,
      joint and muscle symptoms in Papua New Guinea. In the menopause experience,
      significant differences between the cultures are confirmed in favor of a higher
      trait intensity in Papua New Guinea concerning experienced depression, drop in
      performance, sexual disturbances and vaginal dryness. The intra-cultural
      comparison between the concepts concerning menopause and the menopause experience
      in Germany shows a significantly higher trait intensity with regard to the
      expected disturbance from hot flashes, depression, agitation, lack of drive and
      sexual problems as compared to the experienced disturbances. In Papua New Guinea,
      the survey showed a difference in expected and experienced vaginal dryness.
      CONCLUSIONS: Perception and concepts concerning illness and health are based on
      culturally produced patterns.

PMID- 15978967
TI  - Measuring climacteric symptoms in an Ecuadorian population with the Greene
      Climacteric Scale.
AB  - OBJECTIVE: Measure climacteric symptoms in a low socio-economic Ecuadorian
      population with the Greene Climacteric Scale and determine factors involved with
      higher scorings. METHODS: Women aged 40--65, non hormone therapy (HT) users, with
      intact uterus and ovaries, attending the Gynecologic Outpatient Service of the
      Enrique C. Sotomayor Obstetrics and Gynecology Hospital Guayaquil-Ecuador, were
      selected and asked to fill out the Greene Climacteric Scale. RESULTS: During the
      study period, 385 women met inclusion criteria and filled out the climacteric
      scale. Mean age of this sample was 47.6 +/- 5.5 years and 36.6% were aged >or=50
      years. Women were classified as: premenopausal 38.9%, perimenopausal 28.8% and
      postmenopausal 32.3%. The total Greene Climacteric score for postmenopausal was
      found to be higher than premenopausal total score (18.78 +/- 8.11 versus 16.31 +/
      7.62, p < 0.05). Total, clusters and subclusters scorings maintained an
      increasing trend from one menopausal status to the next. The most frequently and
      intensive presenting symptoms of the 21 symptoms composing the scale were:
      difficulty in concentrating, feeling unhappy or distressed, headaches, and hot
      flashes (n=385: 87, 82, 83.9 and 82%, anxiety and depression subclusters, and
      somatic and vasomotor clusters, respectively). Univariate analysis determined
      that age >or=47 years, parity >or=4 and schooling <12 years were associated to
      the risk for having a total Greene scoring of >or=18 (OR: [95% CI], 2.5[1.6-3.8];
      1.8[1.1-3]; 1.6[1-2.7], respectively, p < 0.05). Age >or=47 years was associated
      to increased rates of higher scorings in all clusters except for loss of sexual
      interest, which was contrarily increased together with vasomotor scoring in women
      with higher parity (p < 0.05). Women with educational level <12 years were
      related to higher somatic scorings. Logistic regression analysis confirmed all
      these associations except for parity, which was excluded as a risk factor for
      higher vasomotor scorings. CONCLUSION: In this specific population, climacteric
      symptoms presenting in all menopausal groups, as measured with the Greene
      Climacteric Scale, resulted to be higher than previously reported standards and
      age, parity and educational level were independent risk factors.

PMID- 15978968
TI  - The effect of calcitonin on biochemical markers and zinc excretion in
      postmenopausal osteoporosis.
AB  - OBJECTIVES: A double-blind, randomized, placebo-controlled trial was conducted in
      women with postmenopausal osteoporosis to evaluate effects on biochemical markers
      and urinary excretion of zinc (Zn) of calcitonin therapy. METHODS: Patients were
      required to have a bone mineral density (BMD) of 2.5 S.D. or more below the young
      adult mean either at the postero-anterior lumbar spine or at the femoral neck.
      Subjects were eligible for our study if they were 50 years or older, with at
      least 5 years of menopause, and in good general health as determined by medical
      history and a routine clinical blood analysis. The patients were randomly
      assigned to receive intranasal salmon calcitonin (200 IU/day; 50 patients) or
      placebo (50 patients). All patients received supplemental calcium (1000 mg/day).
      Additionally, 40 age-matched, demographically similar, healthy postmenopausal
      women were also selected as controls. Measurements of cross-linked N-telopeptides
      of type I collagen (uNTx), osteocalcin (sOC), and urinary zinc concentration were
      done. All parameters were measured before therapy and again after 1, 3 and 6
      months. RESULTS: After 3 and 6 months of treatment, a higher decrease of most
      indices was observed in the calcitonin group. A statistically significant
      decrease occurred in the levels of sOC, uNTx and uZn after 3 and 6 months in
      patients receiving calcitonin therapy (P<0.05). Levels of sOC and uNTx in
      calcitonin group were significantly different after 3 and 6 months from both
      placebo and baseline values of calcitonin group (P<0.05). Levels of sOC, uNTx and
      uZn decreased about 40, 46 and 37%, respectively, in calcitonin group at 6 months
      after the start of treatment. CONCLUSIONS: Our study suggests that values of
      uNTx, uZn and sOC were significantly lower in the patient group than those in
      control group and in postmenopausal women with osteopororsis, calcitonin reduces
      the concentrations of uNTx, uZn and sOC.

PMID- 15978969
TI  - Age-related cognitive decline in the menopause: effects of hormone replacement
      therapy on cognitive event-related potentials.
AB  - OBJECTIVE: Although epidemiological and clinical studies suggest that hormone
      replacement therapy (HRT) may protect against cognitive disorders and
      neurodegenerative diseases, the relation between estrogen and cognition in
      postmenopausal women remains controversial. METHODS: In a double-blind placebo
      controlled, parallel group design study the effects of HRT with the estrogen
      progestogen combination Presomen 1.25 compositum((R)) (1.25mg equine conjugated
      estrogens administered for 21 days plus the progestogen 5mg medrogeston given for
      11 days) on event-related potentials (ERPs) in postmenopausal patients with age
      related cognitive decline (DSM-IV code 780.9, ICD-10 code R 41.8) were
      investigated. After a pre-drug comparison with age-matched normal postmenopausal
      controls, 48 psychotropic drug-free patients aged 60 +/- 6 years were randomized
      to receive either placebo or verum for 4 months. ERPs were recorded before as
      well as on the 91-92 days of the study, which thus fell into the estrogen phase
      of the treatment during the fourth cycle. RESULTS: At baseline, patients showed a
      lengthening of P300 latency and an attenuation of P300 amplitudes as compared
      with normal controls. After HRT with Presomen, a significant shortening of P300
      latency as compared with placebo was observed. CONCLUSIONS: The baseline P300
      differences suggest that in the patient group the aging process was advanced,
      while after HRT with Presomen a significant improvement and normalization of
      information processing as indexed by P300 was observed.

PMID- 15978970
TI  - Association of the osteoprotegerin gene polymorphisms with bone mineral density
      in postmenopausal women.
AB  - OBJECTIVES: Osteoprotegerin (OPG) is a recently discovered member of the tumour
      necrosis factor receptor superfamily. It plays a crucial role in the control of
      bone resorption and its gene could therefore be a good candidate gene for
      osteoporosis. The aim of our work was to find polymorphisms in the OPG gene and
      to investigate their possible contribution to the genetic susceptibility to
      osteoporosis by testing for their association with bone mineral density (BMD).
      METHODS: The whole OPG gene coding region was screened for the presence of
      polymorphisms in a group of 60 osteoporotic women by single-strand conformation
      polymorphism analysis (SSCP) approach. Association of the discovered
      polymorphisms with bone mineral density was investigated in 136 Slovenian
      postmenopausal women. RESULTS: We detected eight OPG gene polymorphisms that were
      confirmed by direct DNA sequencing, deletion 4752_4753delCT and nucleotide
      substitutions 1181G>C, 1217C>T, 1284G>A, 4501C>T, 6893A>G, 6950A>C and 8738T>A.
      Nucleotide substitutions 1284G>A and 8738T>A have not been previously described.
      Polymorphisms 4752_4753delCT, 6893A>G and 6950A>C were in complete linkage and
      the same was true for 1217C>T and 4501C>T. The association with BMD was found
      only for polymorphism 1181G>C. Subjects with genotype 1181GG had significantly
      lower lumbar spine BMD than subjects displaying 1181GC. CONCLUSIONS: By our
      approach we detected eight polymorphisms in the OPG gene. According to our
      analysis polymorphism 1181G>C is associated with BMD and could therefore be
      considered as an element of genetic susceptibility to osteoporosis.

PMID- 15978971
TI  - Assessment of DNA damage in postmenopausal women under hormone replacement
      therapy.
AB  - OBJECTIVE: To evaluate the possible DNA damage in peripheral blood leukocytes of
      postmenopausal women under different hormone replacement therapies (HRT), comet
      assay, a standard method for assessing genotoxicity has been used. METHOD: 46
      women were categorized in three groups-Group A: 15 surgical menopausal women who
      underwent surgery for benign conditions, receiving conjugated equine estrogen,
      0.625 mg/day (CEE) for 2.3 +/- 1.5 years, Group B: 16 spontaneous menopausal
      women receiving conjugated equine estrogen, 0.625 mg/day plus medroxyprogesteron
      acetate, 5mg/day (CEE + MPA) for 2.4 +/- 1.0 years and Group C: 15 spontaneous
      menopausal women receiving tibolone, 2.5mg/day for 2.4 +/- 1.3 years. Control
      group consisted of 15 spontaneous menopausal women who never had HRT. RESULTS:
      Significant differences in terms of DNA damage were observed between Group A and
      B with controls as mean total comet scores 23.93 +/- 5.84, 19.44 +/- 6.19 and
      10.07 +/- 2.40, but no significance (P > 0.05) were detected between Group C and
      controls as mean total comet scores 12.07 +/- 3.65 and 10.07 +/- 2.40,
      respectively. CONCLUSION: Reduced DNA damage were observed with tibolone compared
      to CEE or CEE + MPA therapy. Studies of this approach are needed.

PMID- 15978972
TI  - Comparison of effects of the rise in serum testosterone by raloxifene and oral
      testosterone on serum insulin-like growth factor-1 and insulin-like growth factor
      binding protein-3.
AB  - OBJECTIVE: In aging men serum levels of testosterone and insulin-like growth
      factor-1 (IGF-1) decline, potential factors in the reduced muscle strength,
      abdominal obesity, sexual dysfunction and impaired general well being of aging.
      The partial oestrogen agonist and antagonist raloxifene increase serum
      testosterone levels in aging men, but the effect of raloxifene on serum IGF-1
      levels in men is unknown. In this study the effects of raloxifene on IGF-1 levels
      and the associated increase in serum testosterone were compared to the effects of
      oral testosterone supplementation. DESIGN AND PATIENTS: Thirty healthy elderly
      men between 60 and 70 years received raloxifene 120 mg/day or placebo in a
      randomised double blind fashion for 3 months. Secondly, seven female to male (F
      to M) transsexuals undergoing hormonal sex reassignment received testosterone
      undecanoate 160 mg/day. MEASUREMENT: At baseline and after three months serum
      levels of testosterone, IGF-1 and its most important binding protein, IFGBP-3 was
      measured. In the group transsexuals also serum gonadotrophins and 17beta
      oestradiol was measured. RESULTS: Compared to placebo raloxifene increased serum
      testosterone by 20% but it decreased serum IGF-1 levels by 24.5% (95% confidence
      interval (CI): -13.0 to -36.1%). No significant change in serum IGFBP-3 levels
      was found. The effect of raloxifene on serum IGF-1 has been observed with other
      oral oestrogens, and, therefore, is likely to be ascribed to the partial
      oestrogen agonist activity of raloxifene. In the F to M transsexuals, serum
      testosterone levels increased from median <1.0 nmol/l to 6.2 nmol/l, without
      significant changes in serum gonadotrophins and 17beta-oestradiol levels. Serum
      IGF-1 levels increased by 12.1% (95% CI: 1.9-22.3%) versus baseline. No effect
      was observed on serum IGFBP-3 levels. CONCLUSION: Both raloxifene and oral
      testosterone increased serum testosterone, but raloxifene significantly decreased
      serum IGF-1 levels without affecting IGFBP-3. By contrast, oral testosterone
      supplementation in F to M transsexuals increased IGF-1 levels. In both treatment
      groups no significant change in serum IGFBP-3 was found.

PMID- 15978973
TI  - Post-menopausal recurrent vaginal candidiasis: effect of hysterectomy on response
      to treatment, type of colonization and recurrence rates post-treatment.
AB  - INTRODUCTION: Post-menopausal patients are still susceptible to be colonized by
      fungal organisms despite being estrogen-deprived. Symptomatic vulvovaginal
      candidiasis, although a rare occurrence in post-menopausal patients, can be
      diagnosed in about one third of the patients. The purpose of our study was to
      investigate in post-menopausal patients with recurrent vulvovaginal candidiasis
      the effect of hysterectomy on response to treatment, the type of colonization and
      the recurrence rates after treatment. MATERIALS: Forty-seven menopausal patients
      with symptomatic recurrent vulvovaginal colonization were evaluated between
      January 1995 and August 2002. The study was a retrospective cohort chart review
      and included complete history and physical examination, basic metabolic blood
      panel, colposcopy, wet mount, bacterial and fungal cultures. Twenty-three
      patients had hysterectomy and 24 were not hysterectomized. All the patients
      received daily fluconazole therapy for 30 days. They were then re-evaluated at 1,
      3 and 6 months and retreated if symptomatic and culture positive. RESULTS: The 2
      groups of patients were comparable regarding age, number of years of recurrent
      colonization, number of previous antifungal treatments and previous, current use
      of hormone replacement therapy. None used vaginal douching. The 2 groups of
      patients showed statistical differences regarding: colonization by Candida
      albicans (P<0.01), colonization by Candida glabrata (P<0.05), colonization by
      Candida stelloidea (P<0.01), recurrence after 3 months (P<0.05) and 6 months
      (P<0.05), response to one course of therapy (P<0.02) and need for multiple
      treatments (P<0.03). CONCLUSIONS: Hysterectomized post-menopausal patients with
      recurrent vulvovaginal fungal colonization seems to be more propense to harbor
      more aggressive and resistant fungi. Post-menopausal recurrent vaginal
      candidiasis: effect of hysterectomy on response to treatment, type of
      colonization and recurrence rates post-treatment.

PMID- 15978974
TI  - Differential expression of factors involved in fat metabolism with age and the
      menopause transition.
AB  - OBJECTIVES: Changes in the hormonal milieu at the menopause are associated with
      an increase in total adiposity and a more android pattern of fat distribution,
      with the latter associated with an increased risk of the metabolic syndrome. The
      aim of this study was to explore potential mechanisms that might contribute to
      the changes in body composition associated with the menopause transition.
      METHODS: Using real-time PCR analysis, we have compared the expression of various
      factors involved in fat metabolism in subcutaneous abdominal and gluteal fat in
      premenopausal (Group 1; n=11), postmenopausal (Group 2; n=10) and postmenopausal
      women taking estrogen therapy (Group 3; n=10). RESULTS: All subjects were of
      normal body mass index, euglycemic and normolipemic. The postmenopausal women
      were older (Group 1, 43.1+5.0 versus Groups 2 and 3, 57.9+/-7.4 years, P<0.001
      and 56.1+/-4.5 years, P<0.001, respectively). Expression analysis revealed that
      levels of transcripts encoding adiponectin, peroxisome proliferator-activated
      receptor gamma and fatty acid transporter, each associated with insulin
      sensitivity, were significantly greater in gluteal fat from estrogen deplete
      postmenopausal women than in fat from the other two groups (P<0.05). In contrast,
      levels of transcripts for acetyl CoA carboxylase alpha, long chain acyl CoA
      dehydrogenase and hormone sensitive lipase were significantly greater in
      abdominal fat from premenopausal women than either postmenopausal groups
      (P<0.05). CONCLUSIONS: These findings indicate both aging and the menopause
      transition are associated with changes in fat metabolism, which may contribute to
      the accumulation of body fat after menopause.

PMID- 15978975
TI  - Does body mass index reflect adequately the body fat content in perimenopausal
      women?
AB  - OBJECTIVE: To test whether BMI cut-off points for obesity, reflect adequately the
      actual obesity status, in a sample of perimenopausal women. For study's purposes,
      a new bioelectrical impedance analysis (BIA) equation was estimated. METHODS: 115
      Greek, middle-aged women were tested. Body composition was estimated by dual X
      ray absorptiometry and BIA method. Waist (WC) and hip circumference (HC) and
      skinfolds were also measured. RESULTS: The BIA equation predicted fat free mass
      (FFM) from height, weight, age and resistance (R(2)=0.88, S.E.E.=1.89 kg). The
      bias was not significant and the limits of agreement +/-3.6 kg. BMI, FFM, body
      fat percentage (BF%), waist-to-hip ratio (WHR), WC and HC did not differ between
      pre (N=37) and postmenopausal (N=48) women (at p=0.05). Both BF% and BMI
      correlated with WHR and WC (r(BF%-WHR)=0.287, p=0.009; r(BMI-WHR)=0.355, p=0.001
      and r(BF%-WC)=0.72, p<0.0001; r(BMI-WC)=0.81, p<0.0001). The mean values for BF%,
      WC and WHR for women with normal BMI were 36.15% (+/-4.19), 72.53 cm (+/-3.64)
      and 0.749 (+/-0.05), whereas values for overweight women were 41.42% (+/-3.16),
      83.06 cm (+/-7.55) and 0.787 (+/-0.05) and for obese these were 47.40% (+/-3.67),
      95.10 cm (+/-8.52) and 0.814 (+/-0.05), respectively. CONCLUSION: The body
      composition analysis of the study sample revealed undesirably high BF%, even in
      subjects with BMI below 25, in whom BMI did not reflect the body fat content.
      However, BF was mainly distributed at the lower part of the body. Whether BMI or
      BF% is a more sensitive index for obesity related diseases, in perimenopausal
      period, remains to be defined.

PMID- 15978976
TI  - Construction of two instruments for the presumptive detection of post-menopausal
      women with low spinal bone mass by means of clinical risk factors.
AB  - The objective of this investigation was the design of two instruments based on
      clinical risk factors for the presumptive detection of post-menopausal women with
      spinal BMD<2.5 S.D. below average (LBMD). We investigated the association of 20
      risk factors (RF) with LBMD in a series of 131 women. According to current
      densitometric criteria, subjects were classified as normals (N=33); osteopenics
      (N=53) and osteoporotics (N=45). Normals and osteopenics were taken as a single
      group because only 'nulliparity' and 'personal fractures' exhibited significant
      differences between these groups. A logistic regression attempting to identify
      which factors were associated with osteopenia showed a poor fit (pseudo
      R(2)=0.289). Univariate unconditional logistic regression analysis was used to
      calculate odd ratios (ORs) and their 95% CI for all RF. Those with associated P
      values <0.100 were included in a multivariate logistic regression analysis to
      obtain the odds ratios (OR) adjusted by the effects of the others. The variables
      with not significant beta coefficients were eliminated, producing a reduced
      model. BMI (<25 kg/m(2)), calcium intake (<1.2g/day), menopause (>10 years), and
      the simultaneous occurrence of kyphosis and personal fractures showed significant
      association with low bone mass at the lumbar spine and their effect was additive.
      Fitting of the data to the model was assessed with the Hosmer-Lemeshow test
      (P=0.926) The area under the ROC curve is 0.833 (95% CI=0.757-0.909). The
      following equation calculates the probability of having low spinal bone mass: The
      sensitivity, specificity and area under the ROC curve were defined. The point of
      maximum specificity and sensitivity derived from the ROC curve, has a probability
      of 0.409. With such a cut-off point, the equation has a sensitivity of 73%,
      specificity 79%, positive predictive value 65% and negative predictive value 85%.
      The second instrument associates very low lumbar bone mass with the number of
      risk factors accumulated per patient. At baseline, all subjects had four RFs:
      they were, women, white, post-menopausal, and with no previous exposure to
      estrogens. With six additional RFs the presumptive diagnosis of LBMD has a
      specificity of 99%, positive predicting value 94% and false positives 6.5%. The
      area under the curve in a ROC graph was 0.826 (95% CI=0.747-0.914). Comparing
      present instruments with others in the literature, it is concluded that each
      population require its own algorithm for the presumptive detection of subjects
      with low bone mass. The algorithm should be reassessed periodically if the
      characteristics of the population or its social-economic conditions change.

PMID- 15978984
TI  - Effect of processing time on enteric bacteria survival and on temperature and
      chemical composition of broiler poultry litter processed by two methods.
AB  - This study was conducted to evaluate the effects of deepstack processing broiler
      poultry litter with or without aeration on enteric bacteria survival (Trial 1),
      and to determine the optimum aeration period (Trial 2) and aeration frequency
      (Trial 3) to control excessive heating of litter during the deepstacking process.
      The effects of deepstacked litter temperature on bacteria survival and on
      chemical compositions of the litter were monitored. In Trial 1, E. coli,
      Salmonella enteriticis and Shigella sonnei were intentionally inoculated into the
      litter and their survival was monitored with time of litter processing. In Trial
      2, litter was deepstacked and aerated once a day from the initial day or from the
      day when maximum stack temperature was reached and started to decrease to the end
      of processing period. In Trial 3, litter was deepstacked and aerated once or
      twice a day from the day after maximum stack temperature was attained until
      constant temperature was attained. During the deepstacking process of litter
      pathogenic bacteria were eliminated between the 2nd and 4th day of deepstacking.
      This phenomenon occurred apparently not only by high heat generated, but also by
      other potential factors, such as ammonia and microbial competition. Aeration
      resulted in the heat dissipation and early temperature reduction of deepstacked
      litter. The optimum aeration procedure to avoid excessive heating of deepstacked
      litter was to aerate once a day after the stack temperature reached its maximum
      at the early stage of deepstacking and for 3 days or until the stack temperature
      dropped off and reached constancy. This aerating frequency and duration did not
      negatively affect the chemical composition of deepstacked litter. These results
      suggest that poultry litter properly deepstacked, with or without aeration, to
      ensure the elimination of enteric bacterial pathogens may be fed at least 10 days
      earlier than the 21-day deepstacking period previously recommended.

PMID- 15978985
TI  - Improving acidogenic performance in anaerobic degradation of solid organic waste
      using a rotational drum fermentation system.
AB  - The effects of leachate from a methanogenic process on acidogenic performance of
      a solid recycle (SR) process by a rotational drum fermentation (RDF) system were
      evaluated under mesophilic condition and a hydraulic retention time (HRT) of 20
      days. Two SR process configurations, SR1 and SR2, were evaluated, using fresh
      soybean meal or Okara as substrates. An apparent first-order hydrolysis rate
      constant of 5.0 x 10(-3)/d for SR1 at pH values of 4.4 and 14.4 x 10(-3)/d for
      SR2 at pH of 5.0, were obtained. The apparent volatile solids (VS) degradation
      ratio ranged from 9.6% to 19.4% and total volatile acid (as acetic acid) from
      10.8 to 14.9 g/L. Occupying ratios for ionized volatile acid (VA) increased from
      30.6% to 63.4% after recycling the leachate to process. However, occupying ratios
      of acetic acid decreased from 93.3% to 42.0% whereas propionic acid and butyric
      acid ratios increased in SR2. Integrating the VA production with the hydrolysis
      rate constants, it is clear that the recirculation of leachate considerably
      enhanced acidogenic performance of solid recycle process.

PMID- 15978986
TI  - Recovery of phosphorous from swine wastewater through crystallization.
AB  - All the phosphate rock Japan needs must be presently imported from abroad because
      the country has no subterranean phosphorous resources. Therefore, there is a need
      to accelerate the development of and establish the technologies for phosphorous
      recovery from waste and wastewater. Swine wastewater has a high potential for
      phosphorous recovery in Japan. A reactor for removing and recovering phosphorous
      from swine wastewater was designed with dual functions, crystallization through
      aeration and separation of formed struvite by settling. However, a dehydration,
      composting and characterization process was first needed before using sediment
      sludge, including struvite, on farmland, since the struvite will settle along
      with huge amounts of other suspended solids (organic matter). For the recovery of
      pure struvite, an accumulation device was designed and its efficiency examined.
      The device has a struvite-accumulation face made of stainless steel wire mesh (1
      mm in diameter, 1 cm(2) square) to reduce its total weight. During submergence in
      the aeration column of the demonstration reactor, struvite cross-bridged and
      accumulated on the face of the device. The struvite could be scraped off easily
      with only a light brushing, and was found to be approximately 95% pure. Because
      this device is a very simple structure, it is thought to be acceptable to swine
      farmers.

PMID- 15978987
TI  - A diffusion model for drying of a heat sensitive solid under multiple heat input
      modes.
AB  - To obtain optimal drying kinetics as well as quality of the dried product in a
      batch dryer, the energy required may be supplied by combining different modes of
      heat transfer. In this work, using potato slice as a model heat sensitive drying
      object, experimental studies were conducted using a batch heat pump dryer
      designed to permit simultaneous application of conduction and radiation heat.
      Four heat input schemes were compared: pure convection, radiation-coupled
      convection, conduction-coupled convection and radiation-conduction-coupled
      convection. A two-dimensional drying model was developed assuming the drying rate
      to be controlled by liquid water diffusion. Both drying rates and temperatures
      within the slab during drying under all these four heat input schemes showed good
      accord with measurements. Radiation-coupled convection is the recommended heat
      transfer scheme from the viewpoint of high drying rate and low energy
      consumption.

PMID- 15978988
TI  - Sorghum straw for xylanase hyper-production by Thermomyces lanuginosus (D2W3)
      under solid-state fermentation.
AB  - This paper reports the production of very high levels of cellulase free xylanase
      and associated hemicellulases by an indigenous thermophilic isolate of
      Thermomyces lanuginosus (D(2)W(3)) using solid-state fermentation. Sorghum straw,
      an inexpensive and abundant source of carbon supported maximal xylanase activity
      (11,855 units/g dry substrate). Culturing T. lanuginosus D(2)W(3) on sorghum
      straw and optimizing other culture conditions (media types, particle size of
      carbon source, inoculum level, inoculum age and additives), yielded increased
      levels of xylanase (39,726 units/g dry substrate). Further optimization of enzyme
      production was carried out using Box-Behnken design of experiments with three
      independent variables (inoculum level, glycerol and ammonium sulphate
      concentrations) which resulted in very high levels of xylanase, 48,000+/-1774
      units/g dry substrate, and 2.6+/-0.2, 13.4+/-0.56, 68+/-1.7, 1.4+/-0.08, 1.2+/
      0.05 (units/g dry substrate) of beta-xylosidase, alpha-galactosidase, pectinase,
      beta-mannosidase and alpha-L-arabinofuranosidase, respectively.

PMID- 15978989
TI  - Volatilisation of alkali and alkaline earth metallic species during the pyrolysis
      of biomass: differences between sugar cane bagasse and cane trash.
AB  - Sugar cane bagasse and cane trash were pyrolysed in a novel quartz fluidised
      bed/fixed-bed reactor. Quantification of the Na, K, Mg and Ca in chars revealed
      that pyrolysis temperature, heating rate, valence and biomass type were important
      factors influencing the volatilisation of these alkali and alkaline earth
      metallic (AAEM) species. Pyrolysis at a slow heating rate (approximately 10 K
      min(-1)) led to minimal (often <20%) volatilisation of AAEM species from these
      biomass samples. Fast heating rates (>1000 K s(-1)), encouraging volatile-char
      interactions with the current reactor configuration, resulted in the
      volatilisation of around 80% of Na, K, Mg and Ca from bagasse during pyrolysis at
      900 degrees C. Similar behaviour was observed for monovalent Na and K with cane
      trash, but the volatilisation of Mg and Ca from cane trash was always restricted.
      The difference in Cl content between bagasse and cane trash was not sufficient to
      fully explain the difference in the volatilisation of Mg and Ca.

PMID- 15978990
TI  - Adsorption characteristics of malachite green on activated carbon derived from
      rice husks produced by chemical-thermal process.
AB  - Phosphoric acid (H(3)PO(4)) and sodium hydroxide (NaOH) treated rice husks,
      followed by carbonization in a flowing nitrogen were used to study the adsorption
      of malachite green (MG) in aqueous solution. The effect of adsorption on contact
      time, concentration of MG and adsorbent dosage of the samples treated or
      carbonized at different temperatures were investigated. The results reveal that
      the optimum carbonization temperature is 500 degrees C in order to obtain
      adsorption capacity that is comparable to the commercial activated carbon for the
      husks treated by H(3)PO(4). It is interesting to note that MG adsorbed preferably
      on carbon-rich than on silica rich-sites. It is found that the behaviour of
      H(3)PO(4) treated absorbent followed both the Langmuir and Freundlich models
      while NaOH treated best fitted to only the Langmuir model.

PMID- 15978991
TI  - Chemical and biological changes during composting of different organic wastes and
      assessment of compost maturity.
AB  - Changes in organic C, total N, C:N ratio, activities of cellulase, xylanase and
      protease, and microbial population were determined during composting of different
      organic wastes such as mixture of sugarcane trash and cattle dung, press mud,
      poultry waste and water hyacinth biomass. There were losses of N in poultry waste
      and water hyacinth with the effect an initial increase in C:N ratio was observed
      which decreased later on due to decomposition. The activities of cellulase,
      xylanase and protease were maximum between 30 and 60 days of composting in
      various wastes. Similar trend was observed with respect to mesophilic bacterial
      and fungal population. Various quality parameters like C:N ratio, water soluble C
      (WSC), CO(2) evolution and level of humic substances were compared after 90 day
      composting. There was statistically significant correlation between C:N ratio and
      CO(2) evolution, WSC and humic substances. Significant correlation between CO(2)
      evolved and level of humic substances was also observed. The study shows that no
      single parameter can be taken as an index of compost maturity. However, C:N ratio
      and CO(2) evolved from finished compost can be taken as the most reliable indices
      of compost maturity.

PMID- 15978992
TI  - Isolation and characterization of enteric bacteria from the hindgut of Formosan
      termite.
AB  - The Formosan subterranean termite, Coptotermes formosanus Shiraki, is an
      aggressive, invasive termite species that has caused billions of dollars of
      damage across the United States for the past 50 years. Termites depend on
      intestinal microorganisms for cellulose digestion. Symbiotic microorganisms in
      the termite gut play key physiological functions such as cellulose and
      hemicellulose digestion, acetogenesis, hydrogenesis, methanogenesis, sulfate
      reduction, and nitrogen fixation. Additionally, intestinal microbes create
      suitable conditions for symbiotic protozoans through the production of nutrients
      and the maintenance of the pH and the anaerobic conditions in the gut. Although
      extensive research has been done on the symbiotic relationship of these termites
      and the microbes found in its gut, there is little information available on the
      role of facultative anaerobes in the gut. We isolated four enteric bacteria from
      the hindgut of Formosan subterranean termite, C. formosanus. All isolates were
      facultative anaerobes and G-. The isolates were identified as Serratia
      marcescens, Enterobacter aerogens, Enterobacter cloacae, and Citrobacter farmeri
      by using BIOLOG assay and fatty acid methyl ester analysis (FAME). Each isolate
      was characterized using sodium dodecyl sulfate (SDS) polyacrylamide gel
      electrophoresis and biochemical study. This is the first report on the presence
      of facultative microbes in termite gut. Results of this first study on
      facultative microbes in the termite gut indicate that the role of facultative
      organisms in the Formosan termite gut may be to scavenge oxygen and create
      anaerobic conditions for the anaerobic microorganisms, which are essential for
      digestion of cellulose consumed by the termite.

PMID- 15978993
TI  - Dilute acid pretreatment of rye straw and bermudagrass for ethanol production.
AB  - Ethanol production from lignocellulosic materials provides an alternative energy
      production system. Rye and bermudagrass that are used in hog farms for nutrient
      uptake from swine wastewater have the potential for fuel ethanol production
      because they have a relative high cellulose and hemicellulose content. Dilute
      sulfuric acid pretreatment of rye straw and bermudagrass before enzymatic
      hydrolysis of cellulose was investigated in this study. The biomass at a solid
      loading rate of 10% was pretreated at 121 degrees C with different sulfuric acid
      concentrations (0.6, 0.9, 1.2 and 1.5%, w/w) and residence times (30, 60, and 90
      min). Total reducing sugars, arabinose, galactose, glucose, and xylose in the
      prehydrolyzate were analyzed. In addition, the solid residues were hydrolyzed by
      cellulases to investigate the enzymatic digestibility. With the increasing acid
      concentration and residence time, the amount of arabinose and galactose in the
      filtrates increased. The glucose concentration in the prehydrolyzate of rye straw
      was not significantly influenced by the sulfuric acid concentration and residence
      time, but it increased in the prehydrolyzate of bermudagrass with the increase of
      pretreatment severity. The xylose concentration in the filtrates increased with
      the increase of sulfuric acid concentration and residence time. Most of the
      arabinan, galactan and xylan in the biomass were hydrolyzed during the acid
      pretreatment. Cellulose remaining in the pretreated feedstock was highly
      digestible by cellulases from Trichoderma reesei.

PMID- 15978994
TI  - Anaerobic digestion of animal waste: effect of mixing.
AB  - Six laboratory scale biogas mixed anaerobic digesters were operated to study the
      effect of biogas recycling rates and draft tube height on their performance. The
      digesters produced methane at 0.40-0.45 L per liter of digester volume per day. A
      higher methane production rate was observed in unmixed digesters, while increased
      biogas circulation rate reduced methane production. However, different draft tube
      heights caused no difference in the methane production rate. Air infiltration (up
      to 15% oxygen in the biogas) was observed in the digesters mixed by biogas
      recirculation. Slight air permeability of tubing or leakage on the vacuum side of
      the air pump may have caused the observed air infiltration. The similar
      performance of the mixed and unmixed digesters might be the result of the low
      solids concentration (50 g dry solids per liter of slurry) in the fed animal
      slurry, which could be sufficiently mixed by the naturally produced biogas.

PMID- 15978995
TI  - Antioxidant activities of enzymatic extracts from brown seaweeds.
AB  - Potential antioxidative activities of enzymatic extracts from seven species of
      brown seaweeds were evaluated using four different reactive oxygen species (ROS)
      scavenging assays containing DPPH (1,1-diphenyl-2-pricrylhydrazyl) free radical,
      superoxide anion, hydroxyl radical and hydrogen peroxide scavenging assay. The
      brown seaweeds were enzymatically hydrolyzed to prepare water-soluble extracts by
      using five carbohydrate degrading enzymes (Viscozyme, Celluclast, AMG, Termamyl
      and Ultraflo) and five proteases (Protamex, Kojizyme, Neutrase, Flavourzyme and
      Alcalase) of commercial and inexpensive enzymes obtained from Novozyme Co.
      (Novozyme Nordisk, Bagsvaerd, Denmark). The enzymatic extracts exhibited more
      prominent effects in hydrogen peroxide scavenging activity (approximately 90%)
      compared to the other scavenging activities and the activity of enzymatic
      extracts was even higher than that of the commercial antioxidants. In particular,
      Ultraflo and Alcalase extracts of S. horneri were dose-dependent and thermally
      stable. Moreover the two enzymatic extracts strongly inhibited DNA damage
      (approximately 50%). Those extracts showed significantly (p<0.05) remarkable
      scavenging effects in DPPH free radical scavenging assay and the activity
      indicated a marked correlation with phenolic contents. From the results,
      enzymatic extracts of the brown seaweeds might be valuable antioxidative sources.

PMID- 15978996
TI  - Angiotensin I converting enzyme (ACE) inhibitory peptide derived from the sauce
      of fermented blue mussel, Mytilus edulis.
AB  - The angiotensin I converting enzyme (ACE) inhibitory activity of fermented blue
      mussel sauce (FBMS) was investigated. Blue mussels were fermented with 25% NaCl
      (w/w) at 20 degrees C for 6 months and the resultant mixture was passed through a
      40-mesh sieve, desalted using an electrodialyzer and then lyophilized. The IC(50)
      value of FBMS for ACE activity was 1.01 mg/ml. An ACE inhibitory peptide was
      purified from FBMS using Sephadex G-75 gel chromatography, SP-Sephadex C-25 ion
      exchange chromatography and reversed-phase high-performance liquid chromatography
      on a C(18) column. The IC(50) value of purified ACE inhibitory peptide was 19.34
      microg/ml, and 10 amino acid residues of the N-terminal sequence was EVMAGNLYPG.
      The purified peptide was evaluated for antihypertensive effect in spontaneously
      hypertensive rats (SHR) following oral administration. Blood pressure
      significantly decreased after peptide ingestion. This result suggested that FBMS
      may have beneficial effects on hypertension.

PMID- 15978997
TI  - Identification and characterization of a novel peritrophic matrix protein, Ae
      Aper50, and the microvillar membrane protein, AEG12, from the mosquito, Aedes
      aegypti.
AB  - Immuno-screening of an adult Aedes aegypti midgut cDNA expression library with
      anti-peritrophic matrix antibodies identified cDNAs encoding a novel peritrophic
      matrix protein, termed Ae. aegypti Adult Peritrophin 50 (Ae-Aper50), and the
      epithelial cell-surface membrane protein, AEG12. Both genes are expressed
      exclusively in the midguts of adult female mosquitoes and their expression is
      strongly induced by blood feeding. Ae-Aper50 has a predicted secretory signal
      peptide and five chitin-binding domains with intervening mucin-like domains.
      Localization of Ae-Aper50 to the peritrophic matrix was demonstrated by immuno
      electron microscopy. Recombinant Ae-Aper50 expressed in baculovirus-infected
      insect cells binds chitin in vitro. Site-directed mutagenesis was used to study
      the role that cysteine residues from a single chitin-binding domain play in the
      binding to a chitin substrate. Most of the cysteine residues proved to be
      critical for binding. AEG12 has a putative secretory signal peptide at the amino
      terminus and a putative glycosyl-phosphatidylinositol (GPI) anchor signal at its
      carboxyl-terminus and the protein was localized by immuno-electron microscopy to
      the midgut epithelial cell microvilli.

PMID- 15978998
TI  - Antennal expressed genes of the yellow fever mosquito (Aedes aegypti L.);
      characterization of odorant-binding protein 10 and takeout.
AB  - A small cDNA library was constructed from antennae of 100 adult male Aedes
      aegypti yellow fever mosquitoes. Sequencing of 80 clones identified 49 unique
      gene products, including a member of the Odorant Binding Protein family (Aaeg
      OBP10), a homologue of Takeout (Aaeg-TO), and transposable elements of the LINE,
      SINE and MITE classes. Aaeg-OBP10 encodes a 140 amino acid protein including a
      predicted 25 amino acid signal peptide. Aaeg-OBP10 expression was adult male
      enriched, increased with adult age, and greatest in antennae and wings but also
      present in maxillary palps, proboscis and leg. Aaeg-OBP10 is a likely orthologue
      of Agam-OBP10 of the malaria mosquito Anopheles gambiae and shares significant
      similarity with members of the OBP56 gene cluster of Drosophila melanogaster.
      These OBP genes may represent a unified class of OBPs with unique roles in
      chemodetection; the expression pattern of Aaeg-OBP10 suggests it may play a role
      in adult male chemosensory behavior. Aaeg-TO encodes a 248 amino acid protein
      including a predicted 22 amino acid signal peptide. Aaeg-TO is homologous with
      the circadian/feeding regulated D. melanogaster Takeout protein (Dmel-TO) and a
      subclass of Juvenile Hormone Binding Proteins (JHBP) characterized by Moling from
      Manduca sexta; both Dmel-TO and Moling are sensitive to feeding, suggesting Aaeg
      TO might regulate the antennal response to food, host or pheromonal odors in a JH
      sensitive manner. Aaeg-TO was used to identify 25 D. melanogaster and 13 A.
      gambiae homologues by Blast analysis suggesting these may comprise a relatively
      large class of protein involved in the hormonal regulation of behavior.

PMID- 15978999
TI  - Differential expression of two cytochrome P450 genes in compatible and
      incompatible Hessian fly/wheat interactions.
AB  - We have recovered two Hessian fly cytochrome P450 cDNAs from an ongoing midgut
      EST project. CYP6AZ1 and CYP6BA1 represent two new subfamilies within the CYP6
      family. The deduced amino acid sequences for CYP6AZ1 and CYP6BA1 show conserved
      structural and functional domains of insect P450s. Expression analysis with
      reverse transcription-polymerase chain reaction (RT-PCR) indicated that CYP6AZ1
      is midgut specific and induced during active larval feeding, whereas CYP6BA1 was
      expressed in all tissues and developmental stages examined. Further expression
      analysis of CYP6AZ1 with RT-PCR in compatible and incompatible Hessian fly/wheat
      interactions suggested that CYP6AZ1 may be required for larval feeding in
      compatible interactions. These results should lead to a better understanding of
      the Hessian fly/wheat interaction with emphasis on the larval midgut as a
      critical interface with its host plant.

PMID- 15979000
TI  - Molecular cloning and comparative analysis of fibrinogen-related proteins from
      the soft tick Ornithodoros moubata and the hard tick Ixodes ricinus.
AB  - Among disease-vectors, the evolution of the tick innate immune system is still
      lagging when compared to insects. Such an investigation, which was initiated, by
      first cloning and sequencing lectins associated in the innate immunity of
      invertebrates and having fibrinogen related domains, helped in the sequencing of
      cDNA encoding for OMFREP from the soft tick, Ornithodoros moubata. Also obtained
      were Ixoderin A and Ixoderin B cDNA sequences from the hard tick Ixodes ricinus.
      Tissue-specific expression of OMFREP showed that it was present primarily in the
      hemocytes and salivary glands. Ixoderin A besides sharing a similar expression
      profile was also expressed in the midgut. Both showed significantly high homology
      to the lectin Dorin M, from O. moubata. Further, phylogenetic comparisons between
      these molecules of the soft and hard ticks showed their relatedness to
      Tachylectins 5A and 5B, involved in the innate immunity of Tachypleus tridentatus
      and ficolins from both vertebrates and invertebrates. Ixoderin B showing tissue
      specific expression only in the salivary glands and the sequence displaying
      certain motif differences in homology point towards a possible function different
      from the other two molecules. This is the first report of lectin-like sequences,
      with a fibrinogen-domain, from the hard tick I. ricinus and a preliminary
      phylogenetic study of these tick sequences with related fibrinogen-domain
      containing sequences highlights a possible role for them in the innate immunity
      of the ticks.

PMID- 15979001
TI  - Diversity of trypsins in the Mediterranean corn borer Sesamia nonagrioides
      (Lepidoptera: Noctuidae), revealed by nucleic acid sequences and enzyme
      purification.
AB  - The existence of a diverse trypsin gene family with a main role in the
      proteolytic digestion process has been proved in vertebrate and invertebrate
      organisms. In lepidopteran insects, a diversity of trypsin-like genes expressed
      in midgut has also been identified. Genomic DNA and cDNA trypsin-like sequences
      expressed in the Mediterranean corn Borer (MCB), Sesamia nonagrioides, midgut are
      reported in this paper. A phylogenetic analysis revealed that at least three
      types of trypsin-like enzymes putatively involved in digestion are conserved in
      MCB and other lepidopteran species. As expected, a diversity of sequences has
      been found, including four type-I (two subtypes), four type-II (two subtypes) and
      one type-III. In parallel, four different trypsins have been purified from midgut
      lumen of late instar MCB larvae. N-terminal sequencing and mass spectrometric
      analyses of purified trypsins have been performed in order to identify cDNAs
      coding for major trypsins among the diversity of trypsin-like sequences obtained.
      Thus, it is revealed that the four purified trypsins in MCB belong to the three
      well-defined phylogenetic groups of trypsin-like sequences detected in
      Lepidoptera. Major active trypsins present in late instar MCB lumen guts are
      trypsin-I (type-I), trypsin-IIA and trypsin-IIB (type-II), and trypsin-III (type
      III). Trypsin-I, trypsin-IIA and trypsin-III showed preference for Arg over Lys,
      but responded differently to proteinaceous or synthetic inhibitors. As full
      length cDNA clones coding for the purified trypsins were available, three
      dimensional protein models were built in order to study the implication of
      specific residues on their response to inhibitors. Thus, it is predicted that
      Arg73, conserved in type-I lepidopteran trypsins, may favour reversible
      inhibition by the E-64. Indeed, the substitution of Val213Cys, unique for type-II
      lepidopteran trypsins, may be responsible for their specific inhibition by HgCl2.
      The implication of these results on the optimisation of the use of protease
      inhibitors for pest control, and on the identification of endoprotease-mediated
      resistance to Bacillus thuringiensis Cry-toxins is discussed.

PMID- 15979002
TI  - The fate of topically applied fatty acids in the sex pheromone gland of the moth
      Heliothis virescens.
AB  - Deuterium-labeled hexadecanoic acid (D4-16:COOH), a sex pheromone biosynthetic
      intermediate, and heptadecanoic acid (D3-17:COOH), an acid that cannot be
      converted to sex pheromone, were topically applied to the pheromone gland of
      female Heliothis virescens, and the fate of the label determined. Both acids were
      incorporated similarly into the glycerolipids, with by far the greatest amount
      found in the triacylglycerols (TGs), and relatively small amounts found in other
      neutral and polar classes. For D4-16:COOH, the labeled pheromone precursor, (Z)
      11-hexadecenoate, was also found predominantly in the TGs but relatively
      (compared to labeled hexadecanoate) high amounts were also found in the
      phospholipids. Within the TGs, both acids, as well as the pheromone precursor,
      were found almost exclusively on the sn-3 position of the glycerol backbone. This
      demonstrates that the major fate, in the glycerolipids, of free fatty acids is
      addition to 1,2-diacylglycerols. A relatively large amount of the applied acid
      was also found in the gland in the form of the acyl-CoA thioester. In a 24-h time
      course study, this form remained at a relatively high level for the duration of
      the assay, and decreased at a rate comparable to the titer of this acid in the
      TGs, suggesting that titers of fatty acids in the glycerolipids and acyl-CoA
      thioesters may be in equilibrium. A time-course assay with D4-16:COOH
      demonstrated that peak pheromone titer after application was reached before peak
      titers of both total hexadecanoate and hexadecanoyl-CoA. Combined with a dose
      response experiment, which showed that labeled pheromone titer did not increase
      above an applied concentration of 20 mg/ml, these data suggest that the final
      step in pheromone biosynthesis, reduction of Z11-16:Acyl-CoA, may be inhibited by
      increased acyl-CoA titers in the gland. Overall, our data are consistent with the
      glycerolipids modulating acyl-CoA concentrations in the pheromone gland.

PMID- 15979003
TI  - Comparative effects of a non-steroidal ecdysone agonist RH-5992 and 20
      hydroxyecdysone in a lepidopteran cell line (IAL-PID2).
AB  - The non-steroidal ecdysone agonist, RH-5992, exhibits ecdysteroid activities in
      vivo as well as in vitro more effectively than 20-hydroxyecdysone (20E). Using
      the IAL-PID2 cells derived from imaginal wing discs of last larval instar of
      Plodia interpunctella, we investigated the action of RH-5992 in the control of
      cell growth. Its effects on the proliferative activity of IAL-PID2 cells, the
      induction level in G2/M arrest and on the expression rate of Plodia B cyclin
      (PcycB), ecdysone B1-isoform (PIEcR-B1) and Ultraspiracle-2 isoform (PIUSP-2)
      were examined. From these cellular and molecular assays, our results brought
      evidence that RH-5992, like 20E, induced an inhibition on cell proliferation by
      blocking IAL-PID2 cells in G2/M phase. Moreover, this G2/M arrest was preceded by
      a decrease in the expression level of PcycB and a high induction of PIEcR-B1,
      PIUSP-2 mRNAs. Dose-response experiments revealed that RH-5992 was even more
      potent than 20E. On these parameters, we therefore suggest that the differential
      observed in the expression level of USP and EcR by RH-5992 and 20E could
      contribute to the difference observed for the biological potency of these two
      compounds.

PMID- 15979004
TI  - The enzymatic component of Drosophila melanogaster chorion is the Pxd peroxidase.
AB  - In the present study, we demonstrate the isolation and characterization of the
      Pxd cDNA clone, which codes for the Drosophila melanogaster chorion peroxidase.
      This specific peroxidase is involved in the chorion hardening process, through
      protein crosslinking mediated by the formation of di- and tri-tyrosine bonds. The
      Pxd gene product has been identified in crude protein extracts from adult flies
      as three immunoreacting, with the anti-rAePO polyclonal antibody, bands of 77, 67
      and 55 kDa, while in larvae and purified chorions as a unique 55 kDa band.
      Moreover, the mature form of the Pxd recombinant protein was specifically
      recognized by the anti-rAePO antibody as a 77 kDa band, while in the presence of
      H2O2 was able to convert tyrosine residues to di-tyrosine moieties. Northern
      blotting analysis of total RNA preparations revealed distinct molecular weight
      patterns of the Pxd RNA transcripts among adult flies, ovaries and larvae. The in
      situ hybridization clearly shows that the Pxd mRNA is specifically expressed in
      follicle cells during the late stages of oogenesis 11-14, while the reverse
      transcription reactions dictate the stage-specific developmental regulation of
      the Pxd gene. The immunolocalization approach, using the anti-rAePO polyclonal
      antibody, has revealed that the Pxd peroxidase is selectively localized in the
      chorion structures and particularly in the endochorion and innermost chorionic
      layer (ICL).

PMID- 15979005
TI  - Fates and targets of male accessory gland proteins in mated female Drosophila
      melanogaster.
AB  - Male accessory gland proteins (Acps) in Drosophila are components of the seminal
      fluid and are transferred to females during copulation. In mated females, Acps
      enhance egg production, augment sperm storage, induce refractory mating
      behaviors, and affect the female's longevity. To address the functions of eight
      previously uncharacterized Acps and further analyze five others, we determined
      the tissues to which they target after transfer to females. Each Acp has multiple
      targets and is unique in its pattern of localization. Within the reproductive
      tract, Acps target to the uterus, oviduct, sperm storage organs, ovary and
      oocytes. Some Acps also leave the reproductive tract, to enter the hemolymph.
      Some Acps are detected on the surface of eggs laid by mated females but were not
      detectable within those eggs. Our results can help to identify the likely
      functions of these Acps as well as to create models for the mechanism of action
      of Acps.

PMID- 15979006
TI  - Coxibs and NSAIDs--clearing the air.

PMID- 15979007
TI  - Characterisation of human knee meniscus cell phenotype.
AB  - OBJECTIVE: Studies on the biology of the human meniscus cell are scarce. The
      objective of our studies was to assess survival/proliferation of human meniscus
      cells in different culture conditions and to characterize the extracellular
      matrix (ECM) produced by these cells in these artificial environments. The
      composition of this ECM offers a variable to define the distinct meniscus cell
      phenotype. MATERIALS AND METHODS: Human meniscus cells were isolated
      enzymatically from visually intact lateral and medial knee menisci. Cells were
      cultured in monolayer conditions or in alginate gel. The composition of the cell
      associated matrix (CAM) accumulated by the isolated cells during culture was
      investigated and compared to the CAM of articular chondrocytes cultured in
      alginate using flow cytometry with fluorescein isothiocyanate-conjugated
      monoclonal antibodies against type I collagen, type II collagen and aggrecan.
      Additional cell membrane markers analysis was performed to further identify the
      different meniscus cell populations in the alginate culture conditions and
      meniscus tissue sections. Proliferation was analyzed using the Hoechst 33258 dye
      method. In some experiments, the effect of TGFbeta1 on some of these variables
      was investigated. RESULTS: The CAM of monolayer cultured meniscus cells is
      composed of high amounts of type I and II collagen and low amounts of aggrecan. A
      major population of alginate cultured meniscus cells on the other hand
      synthesized a CAM containing high amounts of type I collagen, low amounts of type
      II collagen and high amounts of aggrecan. This population is CD44+CD105+CD34-CD31
      . In contrast, a minor cell population in the alginate culture did not accumulate
      ECM and was mainly CD34+. The CAM of alginate cultured articular chondrocytes is
      composed of low amounts of type I collagen, high amounts of type II collagen and
      aggrecan. The expression of aggrecan and of type II collagen was increased by the
      addition of TGFbeta1 to the culture medium. The proliferation of meniscus cells
      is increased in the monolayer culture conditions. Cell numbers decrease slightly
      in the alginate culture, but can be increased after the addition of TGFbeta1.
      CONCLUSION: These results demonstrate that the human meniscus is populated by
      different cell types which can be identified by a distinct CAM composition and
      membrane marker expression. Unlike the monolayer culture conditions, the alginate
      culture conditions appear to favor a more fibrochondrocyte-like cell accumulating
      a CAM resembling the native tissue composition. This CAM composition is
      distinctly different from the CAM composition of phenotypically stable articular
      cartilage chondrocytes cultured in the same alginate matrix.

PMID- 15979008
TI  - Ultrasonographic findings in knee osteoarthritis: a comparative study with
      clinical and radiographic assessment.
AB  - OBJECTIVE: To compare ultrasonographic (US) findings with clinical and
      radiographic assessment in knee osteoarthritis (OA). METHODS: Fifty patients with
      primary knee OA were studied. Clinical assessment of both knees was performed by
      the same rheumatologist who recorded a visual analogue scale (VAS) for pain
      (VASP). All patients underwent a US examination of their knees by a second
      blinded rheumatologist. Weight-bearing anteroposterior and lateral knee
      radiographs were read by a third blinded rheumatologist who assessed the Kellgren
      and Lawrence (K-L) grade, the femorotibial (FT) space width and the presence of
      patello-femoral degenerative signs. RESULTS: Forty patients had bilateral
      symptomatic knee OA and 10 unilateral symptomatic OA. All knees showed
      radiographic FT degenerative signs. US findings in symptomatic knees were
      effusion (47%), protrusion of the medial meniscus (MMP) with displacement of the
      medial collateral ligament (MCLD) (61%) and Baker's cyst (22%). US effusion, MMP
      and MCLD were associated with a significantly higher VAS score for pain (P<0.05).
      MMP was associated with medial FT space width (P<0.05). Patients who had a
      difference between VAS score for pain in each knee greater than 30 (28 patients)
      showed significantly more unilateral effusion, MMP, MCLD and worse K-L grade in
      the more symptomatic knee than those with a difference lesser than 30 (22
      patients). CONCLUSION: Knee effusion and MMP with MCLD are associated with pain
      in knee OA. In addition, MMP may contribute to the radiographic medial FT space
      narrowing. We propose US for assessing periarticular and intraarticular
      abnormalities involved in the pathophysiology of knee OA.

PMID- 15979009
TI  - Treatment of knee osteoarthritis with pulsed electromagnetic fields: a
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: The investigation aimed at determining the effectiveness of pulsed
      electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee
      by conducting a randomized, double-blind, placebo-controlled clinical trial.
      DESIGN: The trial consisted of 2h daily treatment 5 days per week for 6 weeks in
      83 patients with knee OA. Patient evaluations were done at baseline and after 2
      and 6 weeks of treatment. A follow-up evaluation was done 6 weeks after
      treatment. Activities of daily living (ADL), pain and stiffness were evaluated
      using the Western Ontario and McMaster Universities (WOMAC) questionnaire.
      RESULTS: Within group analysis revealed a significant improvement in ADL,
      stiffness and pain in the PEMF-treated group at all evaluations. In the control
      group there was no effect on ADL after 2 weeks and a weak significance was seen
      after 6 and 12 weeks. Significant effects were seen on pain at all evaluations
      and on stiffness after 6 and 12 weeks. Between group analysis did not reveal
      significant improvements over time. Analysis of ADL score for the PEMF-treated
      group revealed a significant correlation between less improvement and increasing
      age. Analysis of patients <65 years using between group analysis revealed a
      significant improvement for stiffness on treated knee after 2 weeks, but this
      effect was not observed for ADL and pain. CONCLUSIONS: Applying between group
      analysis we were unable to demonstrate a beneficial symptomatic effect of PEMF in
      the treatment of knee OA in all patients. However, in patients <65 years of age
      there is significant and beneficial effect of treatment related to stiffness.

PMID- 15979010
TI  - Prolonged clinical benefit from joint distraction in the treatment of ankle
      osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is a degenerative disabling joint disease
      affecting more than 10% of the adult population. No validated disease-modifying
      treatment is available. Joint distraction is a relatively new approach to the
      treatment of severe ankle OA. Short-term (3 years) clinical benefit has been
      proven, but long-term effects remain to be evaluated. METHODS: Patients with
      severe OA of the tibio-talar joint, who had been treated with Ilizarov joint
      distraction more than 7 years previously, were included. Pre-treatment data were
      obtained by retrospective analysis using questionnaires and patients' charts.
      Post-treatment assessments were undertaken using the same questionnaires and by
      physical examination. Three approaches were used and results were compared: the
      van Valburg score, the Ankle Osteoarthritis Scale (AOS), and a patient
      satisfaction questionnaire. Retrospectively and prospectively obtained data were
      available from eight patients for comparison. RESULTS: Twenty-five out of 27
      patients with severe ankle OA treated with Ilizarov joint distraction could be
      traced. Appropriate retrospective data could not be obtained from three patients.
      Six out of the 22 patients (27%) were failures. In 16 patients (73%), significant
      improvement in all clinical parameters was observed using each of the three
      approaches. Good correlations were found between the results of the three methods
      of assessment and retrospectively obtained pre-treatment values were very similar
      to the prospective data. CONCLUSIONS: In 73% of the patients, significant
      clinical benefit from joint distraction of severe OA ankles was maintained for at
      least 7 years. There is, however, a need for further research to try and predict
      which patients will not respond to this unconventional form of major surgical
      intervention.

PMID- 15979011
TI  - Autologous chondrocyte implantation (ACI) for aged patients: development of the
      proper cell expansion conditions for possible therapeutic applications.
AB  - OBJECTIVE: Proliferation and chondrogenic commitment of cultured articular
      chondrocytes are impaired when cells derive from aged donors. In those subjects
      the feasibility of cell-based therapies for articular surface repair is reduced.
      Moreover, the use of serum as medium supplement elicits non-physiological
      responses in cultured chondrocytes. This study was therefore undertaken to
      identify the expansion culture conditions needed to sustain growth and
      chondrogenic commitment of chondrocytes harvested from aged human subjects.
      DESIGN: Articular cartilage was obtained from aged (69-75 years) and from young
      adult subjects (27-35 years). Chondrocytes were isolated and cultured in serum
      free (SF) or in serum-supplemented [fetal calf serum (FCS)] conditions.
      Chondrocytes were expanded in monolayer for five duplications and processed for
      RNA extraction and reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis. The differentiation potential was assessed by micromass pellet cultures
      before and after expansion in either culture medium, or after a prolonged
      exposure to serum followed by a period in SF condition. RESULTS: Only SF-cultured
      chondrocytes reached five duplications within 25-35 days, maintaining the
      expression of some chondrogenic markers and without altering the levels of active
      matrix metalloproteinase 3 (MMP-3). Only the pellets derived from SF-expanded
      cultures positively stained for cartilage matrix deposition. On the contrary,
      exposure to serum diminished the proliferation capacities, abolished the
      differentiation potential in the same cells and elicited transcription of the MMP
      3 gene. Shifting culture conditions from FCS to SF resumed growth rates but
      proper extracellular matrix deposition was only partially restored. CONCLUSIONS:
      The SF conditions have proven valuable to prime cell proliferation and to sustain
      proper commitment in chondrocytes from aged patients. This culturing approach may
      represent a therapeutic chance extendable to a range of patients normally
      excluded from clinical protocols based on autologous chondrocyte implantation
      (ACI).

PMID- 15979012
TI  - The detached osteochondral fragment as a source of cells for autologous
      chondrocyte implantation (ACI) in the ankle joint.
AB  - OBJECTIVE: Autologous chondrocyte implantation (ACI) has been successfully used
      for the treatment of osteochondral lesions of the talus. One of the main problems
      of this surgical strategy is related to the harvesting of the cartilage slice
      from a healthy knee. The aim of this study was to examine the capacity of
      chondrocytes harvested from a detached osteochondral fragment to proliferate and
      to serve as a source of viable cells for ACI in the repair of ankle cartilage
      defects. METHODS: Detached osteochondral fragments harvested from the ankle joint
      of 20 patients with osteochondral lesions of the talus served as the source of
      human articular cartilage specimens. All of the osteochondral lesions were
      chronic and of traumatic origin. In all cases, the fragments were utilized to
      evaluate the viability and proliferation of the cells, the histological
      appearance of the cartilage tissue and the expression of specific cartilage
      markers by real-time polymerase chain reaction (PCR). In the 16 patients
      scheduled for ACI, the expanded chondrocytes were used for chondrocyte
      implantation. In the other 4 patients, with lesion size <1.5cm(2), microfractures
      were created during the initial arthroscopic step. As a control group, 7 patients
      with comparable osteochondral lesions underwent the same surgery, but received
      chondrocytes harvested from the ipsilateral knee. RESULTS: According to the
      American Orthopaedic Foot and Ankle Scoring (AOFAS) system, patients in the
      experimental group had a preoperative score of 54.2+/-16 points and a
      postoperative one of 89+/-9.6 points after a minimum follow-up time of 12 months
      (P<0.0005). The control group of patients had a preoperative score of 54.6+/-11.7
      points and a postoperative one of 90.2+/-9.7 points at a minimum follow-up time
      of 12 months (P<0.0005). The clinical results of the two groups did not differ
      significantly from each other. Chondrocytes isolated from the detached fragments
      were highly viable, phenotypically stable, proliferated in culture and
      redifferentiated when grown within the three-dimensional scaffold used for ACI.
      The morphological and molecular characteristics of the cartilage samples obtained
      from the detached osteochondral fragments were similar to those of healthy
      hyaline articular cartilage. CONCLUSIONS: The good results achieved with this
      strategy indicate that cells derived from the lesioned area may be useful in the
      treatment of osteochondral defects of the talus.

PMID- 15979013
TI  - Haplotypes of the low-density lipoprotein receptor-related protein 5 (LRP5) gene:
      are they a risk factor in osteoarthritis?
AB  - OBJECTIVE: Several genome-wide scans have revealed an osteoarthritis (OA)
      susceptibility locus on chromosome 11q in close proximity to the low-density
      lipoprotein receptor-related protein 5 (LRP5) gene. The regulation of bone mass
      is under the control of LRP5 and since increased bone mass is thought to play a
      role in the pathology of OA we examined LRP5 polymorphisms and haplotypes to
      determine if variants of this locus may predispose to OA. METHODS: A UK control
      population of 187 individuals was examined for five commonly occurring
      polymorphisms against a cohort of 158 DNAs from patients with knee OA. An
      additional UK cohort was also examined to confirm the findings of the first
      study; this second group consisted of 110 knee OA patients. Haplotype analysis
      was also performed on patient and control DNAs. RESULTS: A study of individual
      polymorphisms revealed no association with disease. However, haplotype analysis
      of the initial two populations revealed a common haplotype (C-G-C-C-A) that
      provided a 1.6-fold increased risk of OA (P(c)=0.021). The data obtained from the
      second cohort confirmed the initial findings, with a 1.6-fold increased risk
      observed within this cohort for the risk haplotype (P=0.012). CONCLUSIONS: A
      closer investigation of LRP5 and associated Wnt signalling molecules in OA will
      help determine disease aetiology and the development of novel treatment
      strategies that specifically target the bone compartment.

PMID- 15979014
TI  - Vulnerability to ROS-induced cell death in ageing articular cartilage: the role
      of antioxidant enzyme activity.
AB  - OBJECTIVES: To test the hypothesis that age-related loss of chondrocytes in
      cartilage is associated with impaired reactive oxygen species (ROS) homeostasis
      resulting from reduced antioxidant defence. METHODS: Cell numbers: The total
      number of chondrocytes in the articular cartilage of the femoral head of young,
      mature and old rats was estimated using an unbiased stereological method. ROS
      quantification: Fluorescence intensity in chondrocytes was quantified using the
      oxygen free radical sensing probe dihydrorhodamine 123 (DHR 123), confocal laser
      scanning microscopy and densitometric image analysis. In order to delineate the
      reactive species, explants were pre-treated with N-acetylcysteine (NAC) or N(G)
      nitro-l-arginine methyl ester (l-NAME) prior to ROS quantification. Induction of
      intracellular ROS: Explants were incubated in the redox-cycling drug menadione
      after which they underwent ROS quantification and cell-viability assay.
      Antioxidant enzyme activity: The activity of catalase, superoxide dismutase (SOD)
      and glutathione peroxidase (GPX) was measured. RESULTS: Chondrocyte numbers: A
      significant and progressive loss of chondrocytes was observed with ageing.
      Cellular ROS levels: A significant age-related increase in cellular ROS-induced
      fluorescence was demonstrated. NAC significantly reduced ROS levels in old
      chondrocytes only. Induction of intracellular ROS: Menadione increased cellular
      ROS levels dose-dependently in young and old chondrocytes, with a greater effect
      in the latter. Old chondrocytes were more vulnerable to menadione-induced
      cytotoxicity. Antioxidant enzymes: Catalase activity declined significantly in
      aged cartilage whilst SOD and GPX activities were unaltered. CONCLUSIONS:
      Substantial loss of chondrocytes occurs in rat articular cartilage which may
      result from increased vulnerability to elevated intracellular ROS levels,
      consequent upon a decline in antioxidant defence.

PMID- 15979015
TI  - Do psychological factors increase the risk for back pain in the general
      population in both a cross-sectional and prospective analysis?
AB  - This study aimed to conduct a comprehensive evaluation of background, individual
      and workplace psychological risk factors to investigated their relationship with
      spinal pain. Because there is some doubt as to whether the results of cross
      sectional findings hold in longitudinal studies, a prospective study was
      superimposed upon a cross-sectional design of the effects of psychological
      variables on back pain and function to determine, whether similar results are
      obtained. Participants were workers randomly selected from the general
      population, where 372 had not experienced pain during the past year, and 209 had
      experienced considerable pain problems. A cross-sectional comparison of these
      groups using multivariate statistics indicated that the most potent risk factors
      were psychological distress (odds ratio=13.2) and poor function (odds ratio=6.4).
      Much smaller levels of risk were found for perceived workload, gender and foreign
      birth. Those participants with no pain were followed for one year to determine
      development of a spinal pain problem. Although few participants developed a
      significant pain problem, the prospective analyses showed that psychological
      distress (odds ratio=2.2), catastrophizing (odds ratio=3.0), and workload (odds
      ratio=2.3) produced the highest odds ratios. Taken together these results
      underscore the need for a multidimensional view of the development of pain
      disability. Moreover, individual psychological factors such as distress and
      catastrophizing as well as work place factors like work load were found to be
      highly related to the development of back pain in a sample of workers from the
      general population. The cross-sectional and prospective results were similar in
      character and demonstrate that cross-sectional studies may provide valuable
      information. Because psychological variables were relevant very early on, these
      factors may be important targets for pain prevention programs.

PMID- 15979016
TI  - Spinal cord stimulation in sympathetically maintained complex regional pain
      syndrome type I with severe disability. A prospective clinical study.
AB  - BACKGROUND AND PURPOSE: In this prospective trial we assessed the long-term
      effect of spinal cord stimulation (SCS) on the improvement of functional status
      in complex regional pain syndrome type I (CRPS I). METHODS: A prerequisite for
      eligibility to SCS treatment was the responsiveness of patients to sympathetic
      nerve block. In 29 patients with chronic sympathetically maintained CRPS I, the
      efficacy of SCS on deep pain, allodynia and functional disability was determined.
      Pain intensity was estimated during SCS free intervals of 45 min (inactivation
      test) every 3 months and compared with that under SCS treatment. RESULTS: On SCS
      treatment, both deep pain and allodynia could be permanently reduced from 10 to 0
      2 on a 10 cm visual analogue scale (VAS) (p<0.01). During the inactivation tests,
      reoccurrence of pain up to 8 VAS (quartiles 6-8) was measured. Considerable
      impairments in daily living activities, objectified by the pain disability index,
      were also restored (p<0.01). After a follow-up period of 35.6+/-21 months, 12 of
      16 patients with affected upper limb showed significant increase of the fist grip
      strength from 0 to 0.35 (quartiles 0.1-0.5) kg compared with 0.9 (quartiles 0.7
      1.1) kg on the unaffected side (p<0.01). Eight of ten patients with lower limb
      disability resumed walking without crutches. Previous pain medication could be
      significantly reduced (p<0.01). CONCLUSIONS: As a result of permanent pain relief
      under long-term SCS combined with physiotherapy, the functional status and the
      quality of life could be significantly improved in sympathetically maintained
      CRPS I.

PMID- 15979017
TI  - The influence of non-specific low back pain on pressure pain thresholds and
      disability.
AB  - The purpose of this study was to investigate the pressure pain thresholds (PPTs)
      with respect to the Erector spinae and the hip muscles in 87 patients with
      subacute non-specific low back pain (LBP) and to evaluate the relationship
      between the PPTs and disability. In order to establish reference values, 64
      healthy subjects were examined with respect to PPTs and used as a control group
      against the group of LBP patients. The mean PPT values of the Erector spinae and
      the hip at all examined points of the LBP group were significantly lower
      (p<0.001) in comparison to the PPT values of the healthy group. An exceptionally
      high difference (2.7 kg/cm2) was found at the L3 Erector spinae level. The
      correlation between having LBP or not in the whole group (n=151) and PPT, was
      highest at the L3 level of the Erector spinae (r=-0.710, p<0.001). When the group
      of patients with LBP was divided into two subgroups in terms of having an
      Oswestry disability index (ODI) lower than 40 ("moderate LBP disability") or an
      ODI higher than 40 ("severe LBP disability") it was surprising to notice that
      there was no significant difference between the PPTs of the Erector spinae and
      the hip musculature. This study has shown the possibility of the existence of
      muscular disorder in the lumbar part of the Erector spinae in patients with non
      specific low back pain, but also reveals the strong inter-individual differences
      in muscular fibrosis sensitivity and pain behaviour related to gender.

PMID- 15979018
TI  - Cough headache: frequency, characteristics and the relationship with the
      characteristics of cough.
AB  - Cough headache (CH) is a relatively rare, but an important complication of cough.
      The aim of this cross-sectional clinical study was to evaluate the frequency,
      characteristics and etiology of CH among the patients referred to our Outpatient
      Department with the complaint of cough, and to investigate the relationship
      between their cough and headache characteristics. We evaluated 96 females and 69
      males, a total of 165 patients with cough. Among those, 57 patients (34.5%) had
      one or more cough complications and 32 patients (19.3%) were diagnosed as CH.
      Although it was known that most of the patients with CH had benign headache
      characteristics, the ratio of the symptomatic CH was not low (37.5% of the CH
      patients and 7% of patients with cough). Also, there was a significant
      correlation between the frequency of cough and the severity of headache. Logistic
      regression analysis showed that the incidence of CH was increased 0.4-fold, when
      frequency of cough increased. Age, sex, tobacco use ad the duration of cough were
      not found to be predictive factors for CH. Logistic regression analysis showed
      that the rate of cough complications increased 2.08-fold, when the duration of
      cough was longer than eight weeks (p=0.03) and 0.4-fold when the frequency of
      cough increased (p=0.02). In conclusion, CH is a relatively rare, but an
      important complication of cough and it commonly has an effective treatment
      available. Radiological work-up was crucial in ruling out other causes of
      headache and to confirm that the CH was truly benign.

PMID- 15979019
TI  - Beliefs about appropriate pain behavior: cross-cultural and sex differences
      between Japanese and Euro-Americans.
AB  - The Appropriate Pain Behavior Questionnaire (APBQ) was employed to examine the
      effects of the participants' sex and culture on their beliefs regarding gender
      appropriate pain behavior. The APBQ examines beliefs about the social
      acceptability to male and female participants of the behavioral and verbal
      expressions of pain by men and women (referents) in the presence of others
      [Nayak, S., 2000. Cross Cult Research 34, 135-151]. The participants were 18 male
      and 14 female Japanese, and 11 male and 21 female Euro-Americans. There was a
      significant effect of sex: female participants considered pain behaviors more
      acceptable than male participants. There was a significant effect of culture:
      compared to both male and female Japanese, Euro-American participants rated pain
      behaviors in both sexes to be more acceptable. There was also a significant
      effect of referent gender: for both sexes in both cultures, pain behaviors in
      women were rated as more acceptable than in men. Furthermore, a significant
      interaction was found between referent gender and sex of the participant: Male
      and female participants of both cultures were equally accepting of pain behaviors
      in women, but male participants were less accepting of pain behaviors in men than
      in women. There also was a significant interaction between referent gender and
      culture of the participant: Japanese participants considered pain behavior in
      both genders to be less acceptable than did Americans. The results are explained
      in terms of cultural traditions and social roles, and have clear implications for
      clinical treatment and diagnosis.

PMID- 15979020
TI  - Pain in pediatric oncology--children's and parents' perspectives.
AB  - There is a lack of valid epidemiological data on malignancy-associated pain in
      modern pediatric oncology. Pediatric oncology patients (self-assessment) and
      their parents from 28 hospitals were questioned using age-adapted, structured
      interviews and validated pain assessment tools. Pain intensity was measured by
      the NRS and Bieri faces scale. We conducted 363 interviews with patients and
      their parents, and 46 with the parents alone (if patients <2.5 years). Pain was
      reported at the time of the interview or within the last 24 h, 7 d, or 4 weeks in
      15%, 28%, 50% and 58% of cases, respectively. The proportion of patients
      suffering severe to maximal pain (NRS>3; Bieri>2) increased significantly
      (p=0.001, chi2 test). The median pain intensity for the most severe pain episode
      within the last 4 weeks was 6.7 (NRS 0-10). Adverse effects of anti-tumor therapy
      were the most frequent cause of pain. Multivariate analyses depicted general
      physical condition either "severely reduced" (ASA status 3) (OR 4.0, 95% CI 1.1
      14.7, p=0.037) or "moderately reduced" (ASA status 2) (OR 1.8, 95% CI 1.1-2.9,
      p=0.018), "in-patient status" (OR 1.8, 95% CI 1.2-2.9, p=0.010), and "co
      morbidity present" (OR 3.5, 95% CI 1.1-10.7, p=0.030) as risk factors for severe
      to maximal pain. General anesthesia was the only factor significantly (OR 0.14,
      95% CI 0.05-0.39, p<0.01) associated with a reduction in the proportion of
      patients suffering severe to maximal pain during bone marrow aspiration. Our data
      emphasize both the importance of in-house acute pain control and the need for
      general anesthesia during painful procedures in pediatric oncology.

PMID- 15979021
TI  - The effect of venlafaxine on ongoing and experimentally induced pain in
      neuropathic pain patients: a double blind, placebo controlled study.
AB  - BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled
      study was to investigate the effectiveness and the safety of venlafaxine XR 75
      and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with
      neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing
      pain intensity (VAS), patient satisfaction, side effects, global efficacy and
      tolerance. Quantitative sensory measurements taken from the affected area before
      and after the drug treatment included pin-prick hyperalgesia, allodynia,
      detection and pain thresholds to electrical and heat stimuli, temporal summation
      of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients
      completed the study. VAS scores decreased significantly compared to the baseline
      measurements in all groups. There was no significant difference between the
      groups regarding pain intensity and escape medication. The areas of allodynia and
      pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to
      the placebo. There was no significant difference between the groups regarding the
      detection thresholds (electrical and heat). The pain threshold and the summation
      threshold to electrical stimuli and the summation threshold to heat stimuli
      increased significantly following treatment in both venlafaxine groups. In
      addition, the degree of the temporal summation to electrical and heat stimuli
      decreased significantly following treatment in both venlafaxine groups compared
      to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in
      the manifestations of hyperalgesia and temporal summation, but not on the ongoing
      pain intensity. Furthermore, the quantitative sensory tests provided
      complementing information to the clinical measures.

PMID- 15979022
TI  - Decline in physical activity, disability and pain-related fear in sub-acute low
      back pain.
AB  - AIM OF INVESTIGATION: To evaluate whether a perceived decline in the level of
      physical activity after the onset of pain (PAD) is more appropriate in the
      explanation of disability as compared to the actual level of physical activity
      (PAL) in patients with sub-acute back pain. METHODS: Patients with 4-7 weeks of
      non-specific low back pain (LBP) participated in this study. Their habitual
      physical activity level before the back pain started (H-PAL), their actual level
      of physical activity (PAL) and their perceived decline in the level of physical
      activity after the onset of pain (PAD) were assessed. The association between
      these physical activity related variables and perceived disability (QBPDS), fear
      of movement/(re)injury (TSK), pain catastrophizing (PCS) and pain intensity (VAS)
      was examined. The role of PAD as a mediator in the association between fear of
      movement/(re)injury and disability was examined by three linear regression
      analyses. RESULTS: 123 patients (66 male and 57 female) with a mean age of 44.1
      years (SD=10.3) participated in this study. PAD was significantly correlated with
      disability, fear of movement/(re)injury, pain catastrophizing and pain intensity.
      PAD and PAL appeared more important in the explanation of disability in the
      subgroup of patients who were physically active before their back pain started.
      Generally, PAD indeed mediated the association between fear of
      movement/(re)injury and disability. CONCLUSIONS: The perceived decline in
      physical activity, rather than the current physical activity itself is important
      in the evaluation of the impact of activity related changes on disability in low
      back pain.

PMID- 15979023
TI  - When sex hurts, anxiety and fear orient attention towards pain.
AB  - Hypervigilance for pain-relevant stimuli has been associated with anxiety, fear
      of pain and anxiety sensitivity. This attentional bias has been primarily
      investigated in heterogeneous pain groups or pain-free controls, but has not been
      examined in pain conditions where anxiety and fear are likely to play a central
      role. Due to the intimate and interpersonal nature of genital pain experienced
      during sexual intercourse, Vulvar Vestibulitis Syndrome (VVS) constitutes an
      ideal sample in which to investigate the role of cognitive and affective factors
      in pain perception and maintenance. Seventeen women suffering from VVS and an
      equal number of age and education matched control women completed an emotional
      Stroop and memory recall task in addition to a series of questionnaires assessing
      pain-hypervigilance, state and trait anxiety, fear of pain, and anxiety
      sensitivity. VVS sufferers reported hypervigilance for coital pain and also
      exhibited a selective attentional bias towards pain stimuli on the emotional
      Stroop task as compared with controls. This effect was predicted by state and
      trait anxiety and fear of pain. According to these data, treament strategies for
      VVS should target anxiety and fear in addition to sensory systems.

PMID- 15979024
TI  - Acupuncture for the relief of cancer-related pain--a systematic review.
AB  - AIMS: This systematic review summarises the existing evidence on acupuncture for
      cancer-related pain. METHODS: Literature searches were conducted in seven
      databases. All clinical studies of acupuncture, electroacupuncture and ear
      acupuncture in cancer patients with the main outcome measure of pain were
      included. Data were extracted according to pre-defined criteria by two
      independent reviewers and methodological quality was assessed using the Jadad
      scale. RESULTS: Of the seven studies included, one high quality randomised
      clinical trial of ear acupuncture showed statistically significant pain relief in
      comparison with placebo ear acupuncture. All the other studies were either non
      blinded (n=2) or uncontrolled clinical trials (n=4). Most investigations suffered
      from methodological flaws such as inadequate study design, poor reporting of
      results, small sample size and overestimation of the results. CONCLUSIONS: The
      notion that acupuncture may be an effective analgesic adjunctive method for
      cancer patients is not supported by the data currently available from the
      majority of rigorous clinical trials. Because of its widespread acceptance,
      appropriately powered RCTs are needed.

PMID- 15979025
TI  - Ultrasound vocalisation by rodents does not correlate with behavioural measures
      of persistent pain.
AB  - Three well-established rodent models of somatic, visceral and neuropathic pain
      were used to test the hypothesis that a stress and anxiety evoked behaviour,
      namely ultrasound vocalisation, correlates with other well-characterised indices
      of pain behaviour, such as limb withdrawal and stereotypical behaviour.
      Persistent pain presents a significant clinical problem for which there remains
      relatively ineffective clinical management and animal models of pain are commonly
      employed to investigate the underlying pathophysiology and for pre-clinical
      evaluation of novel therapies. At present, the assessment of such animal models
      largely relies on the observation of simple reflex responses which may not
      entirely represent the full range of rodent pain behaviour. Therefore, additional
      integrated behavioural indices for the quantification of pain could improve the
      veracity of animal models. In stressful or harmful situations, it is thought that
      rodents produce ultrasound vocalisations to communicate within the social group.
      In this study, the number of ultrasound vocalisations (22 kHz) was measured
      during both evoked and ongoing pain. Ultrasound vocalisation was not associated
      with other pain behaviour in any of the inflammatory, visceral or neuropathic
      pain models examined and is therefore not a useful integrated correlate of pain
      behaviour.

PMID- 15979026
TI  - Neuropsychological assessment of chronic non-malignant pain patients treated in a
      multidisciplinary pain centre.
AB  - The aim of the study was to investigate the influence of pain, sedation, pain
      medications and socio-demographics on cognitive functioning in chronic non
      malignant pain patients. Chronic non-malignant pain patients (N=91) treated in a
      multidisciplinary pain centre were compared with age and sex matched healthy
      volunteers (N=64). Furthermore four subgroups of patients were examined: Group 1
      (N=21) received no pain medications, group 2 (N=19) were in long-term oral opioid
      treatment, group 3 (N=18) were treated with antidepressants and/or
      anticonvulsants and group 4 (N=33) were treated with a combination of long-term
      oral opioids and antidepressants and/or anticonvulsants. Assessments comprised
      pain (PVAS) and sedation (SVAS), Continuous Reaction Time (CRT) testing for
      sustained attention, Finger Tapping Test (FTT) testing for psychomotor speed,
      Paced Auditory Serial Addition Task (PASAT) testing for information processing
      and working memory and Mini Mental State Examination (MMSE). CRT and FTT were
      impaired in the total patient sample. Treatment with opioids was associated with
      poorer performance of PASAT. High scores of PVAS and SVAS were associated with
      poor performance of PASAT and CRT, respectively. MMSE seems to be too insensitive
      for detecting the milder forms of cognitive impairment found in chronic non
      malignant patients.

PMID- 15979027
TI  - Human brain mechanisms of pain perception and regulation in health and disease.
AB  - CONTEXT: The perception of pain due to an acute injury or in clinical pain states
      undergoes substantial processing at supraspinal levels. Supraspinal, brain
      mechanisms are increasingly recognized as playing a major role in the
      representation and modulation of pain experience. These neural mechanisms may
      then contribute to interindividual variations and disabilities associated with
      chronic pain conditions. OBJECTIVE: To systematically review the literature
      regarding how activity in diverse brain regions creates and modulates the
      experience of acute and chronic pain states, emphasizing the contribution of
      various imaging techniques to emerging concepts. DATA SOURCES: MEDLINE and PRE
      MEDLINE searches were performed to identify all English-language articles that
      examine human brain activity during pain, using hemodynamic (PET, fMRI),
      neuroelectrical (EEG, MEG) and neurochemical methods (MRS, receptor binding and
      neurotransmitter modulation), from January 1, 1988 to March 1, 2003. Additional
      studies were identified through bibliographies. STUDY SELECTION: Studies were
      selected based on consensus across all four authors. The criteria included well
      designed experimental procedures, as well as landmark studies that have
      significantly advanced the field. DATA SYNTHESIS: Sixty-eight hemodynamic studies
      of experimental pain in normal subjects, 30 in clinical pain conditions, and 30
      using neuroelectrical methods met selection criteria and were used in a meta
      analysis. Another 24 articles were identified where brain neurochemistry of pain
      was examined. Technical issues that may explain differences between studies
      across laboratories are expounded. The evidence for and the respective incidences
      of brain areas constituting the brain network for acute pain are presented. The
      main components of this network are: primary and secondary somatosensory,
      insular, anterior cingulate, and prefrontal cortices (S1, S2, IC, ACC, PFC) and
      thalamus (Th). Evidence for somatotopic organization, based on 10 studies, and
      psychological modulation, based on 20 studies, is discussed, as well as the
      temporal sequence of the afferent volley to the cortex, based on neuroelectrical
      studies. A meta-analysis highlights important methodological differences in
      identifying the brain network underlying acute pain perception. It also shows
      that the brain network for acute pain perception in normal subjects is at least
      partially distinct from that seen in chronic clinical pain conditions and that
      chronic pain engages brain regions critical for cognitive/emotional assessments,
      implying that this component of pain may be a distinctive feature between chronic
      and acute pain. The neurochemical studies highlight the role of opiate and
      catecholamine transmitters and receptors in pain states, and in the modulation of
      pain with environmental and genetic influences. CONCLUSIONS: The nociceptive
      system is now recognized as a sensory system in its own right, from primary
      afferents to multiple brain areas. Pain experience is strongly modulated by
      interactions of ascending and descending pathways. Understanding these modulatory
      mechanisms in health and in disease is critical for developing fully effective
      therapies for the treatment of clinical pain conditions.

PMID- 15979028
TI  - D-amino acids in the central nervous system in health and disease.
AB  - Recent evidence has shown that d-amino acids are present in animals and humans in
      high concentrations and fulfill specific biological functions. In the central
      nervous system, two d-amino acids, d-serine and d-aspartate, occur in
      considerable concentrations. d-Serine is synthesized and metabolized endogenously
      and the same might account for d-aspartate. d-Serine has been studied most
      extensively and was shown to play a role in excitatory amino acid metabolism,
      being a co-agonist of the N-methyl-d-aspartate (NMDA) receptor. Insight into d
      serine metabolism is relevant for physiological NMDA receptor (NMDAr) activation
      and for all the disorders associated with an altered function of the NMDAr, such
      as schizophrenia, ischemia, epilepsy, and neurodegenerative disorders. d
      Aspartate appears to play a role in development and endocrine function, but the
      precise function of d-aspartate and other d-amino acids in animals and humans
      requires further investigation. As d-amino acids play biological roles,
      alterations in the concentrations of d-amino acids might occur in some disorders
      and relate to the pathogenesis of these disorders. d-Amino acid concentrations
      may then not only help in the diagnostic process, but also provide novel
      therapeutic targets. Consequently, the presence and important roles of d-amino
      acids in higher organisms do not only challenge former theories on mammalian
      physiology, but also contribute to exciting new insights in human disease.

PMID- 15979029
TI  - Short-term, high dose enzyme replacement therapy in sialidosis mice.
AB  - Given the success of enzyme replacement therapy (ERT) in treating the systemic
      manifestations in a number of lysosomal storage disorders (LSDs), we evaluated
      the effect of ERT on the mouse model of sialidosis. This glycoproteinosis, which
      affects primarily the reticuloendothelial (RE) system, is caused by deficiency of
      lysosomal neuraminidase (NEU1) and consequent accumulation of sialylated
      glycoconjugates. NEU1 lacks a functional mannose-6-phosphate recognition marker
      and is not endocytosed by mammalian cells. However, the enzyme produced in insect
      cells has features that allow its effective uptake by RE cells and macrophages
      via the mannose receptor, and therefore represent an alternative method of
      therapy. In this study we tested the therapeutic efficacy of baculovirus (BV)
      expressed mouse neuraminidase (Neu1) in sialidosis mice. Four-week-old Neu1-/-
      mice were first injected intravenously with a single dose of the recombinant
      enzyme for assessment of the half-life of mannosylated Neu1 in vivo. Afterwards,
      a short-term ERT with a total of five enzyme injections over a 2-week period was
      performed for evaluation of phenotype correction. Neu1 infused alone or co
      administered with its associated protein, protective protein/cathepsin A (PPCA)
      was effectively taken up by resident macrophages in many tissues. Restored Neu1
      activity persisted for up to 4 days, depending on the tissue, and resulted in a
      significant reduction of lysosomal storage. However, beyond 2 weeks of treatment,
      ERT mice developed a severe immune response towards the exogenous Neu1 enzyme.
      These results may have important implications for ERT in sialidosis patients.

PMID- 15979030
TI  - Characterization of phytanic acid omega-hydroxylation in human liver microsomes.
AB  - Phytanic acid is a 3-methyl branched-chain fatty acid which originates from
      dietary sources. Since the 3-methyl group blocks regular beta-oxidation, it is
      broken down by peroxisomal alpha-oxidation. Adult Refsum disease patients
      accumulate phytanic acid as a result of an impairment in peroxisomal alpha
      oxidation, caused by the deficient activity of the enzyme phytanoyl-CoA
      hydroxylase in the majority of patients. In this paper, we studied an alternative
      degradation route for phytanic acid, namely omega-oxidation. During omega
      oxidation a fatty acid is hydroxylated at its omega-end by a member of the
      cytochrome P450 multi-enzyme family. Subsequently, an alcohol dehydrogenase
      converts the formed hydroxyl group into an aldehyde, which is then converted into
      a carboxyl-group by an aldehyde dehydrogenase. In case of phytanic acid omega
      hydroxylation would lead to the formation of phytanedioic acid, which can be
      degraded by beta-oxidation from the omega-end. Here, we show that phytanic acid
      indeed undergoes omega- and (omega-1)-hydroxylation in pooled human liver
      microsomes in an NADPH-dependent manner with a ratio of 15:1. Studies with
      imidazole antimycotics indicate that these reactions are catalyzed by one or more
      cytochrome P450 enzymes. Induction of the cytochrome P450 involved in phytanic
      acid omega-hydroxylation may increase the flux through the omega-oxidation
      pathway, causing increased clearance of phytanic acid in ARD patients. Hence,
      this alternative catabolic pathway is of potential therapeutic relevance.

PMID- 15979031
TI  - Non-invasive screening method for Fabry disease by measuring
      globotriaosylceramide in whole urine samples using tandem mass spectrometry.
AB  - Fabry disease is an X-linked sphingolipidosis due to a deficiency of alpha
      galactosidase A, which leads to the accumulation of globotriaosylceramide (GL-3)
      in several organs. When recombinant human alpha-galactosidase A is intravenously
      administered repeatedly before the patient develops permanent tissue damage,
      there is evidence that the accumulation of GL-3 is decreased in some organs and
      that the clinical symptoms are alleviated in some patients. However, Fabry
      disease is rare and many patients are not diagnosed until adulthood after
      irreversible tissue damage has occurred. Our group has developed a simple and non
      invasive screening method for Fabry disease that measures total GL-3 in whole
      urine samples by tandem mass spectrometry. Using this method, we found that the
      concentration of GL-3 in whole urine sample from hemizygous patients, including
      pre-symptomatic young children with classic type Fabry disease, was significantly
      higher than that in controls. The mean concentration of GL-3 in urine from
      heterozygotes with symptoms was significantly higher than control concentrations,
      but GL-3 levels in the urine from 2 out of 8 heterozygotes of classic type Fabry
      disease were within control levels. An asymptomatic 14-year old hemizygote in the
      family of a cardiac variant did not have elevated urinary GL-3. Therefore,
      screening for the classic type and probably renal variant of Fabry disease is
      possible by measuring urinary GL-3, using our method. The early diagnosis of
      cardiac variant hemizygotes and some heterozygotes with all types of Fabry
      disease will not be possible using our method. We propose that this procedure can
      be used as a reliable, non-invasive, simple method for general and high-risk
      population screening for hemizygotic patients with the classic type and probably
      renal variant of Fabry disease.

PMID- 15979032
TI  - Over-expression of human lysosomal alpha-mannosidase in mouse embryonic stem
      cells.
AB  - Alpha-mannosidosis is a lysosomal storage disorder characterised by the lysosomal
      accumulation of mannose-containing oligosaccharides and a range of pathological
      consequences, caused by a deficiency of the lysosomal enzyme alpha-mannosidase.
      One of the major features of alpha-mannosidosis is progressive neurological
      decline, for which there is no safe and effective treatment. Implantation of stem
      cells into the central nervous system has been proposed as a potential therapy
      for these disorders. We report the construction and characterisation of mouse
      embryonic stem cell lines for the sustained over-expression of recombinant human
      lysosomal alpha-mannosidase (rhalphaM). Two vectors (involving recombinant human
      alpha-mannosidase expression driven by either the chicken beta-actin promoter/CMV
      enhancer or by the elongation factor 1-alpha promoter) were constructed and used
      to transfect mouse D3 embryonic stem cells. Selected clonal cell lines were
      isolated and tested to evaluate their expression of recombinant human alpha
      mannosidase. Stem cell clones transfected with the chicken beta-actin
      promoter/CMV enhancer maintained rhalphaM expression levels throughout
      differentiation. This expression was not markedly elevated above background. In
      contrast, the vector incorporating the elongation factor 1-alpha promoter
      facilitated substantial over-expression of alpha-mannosidase when analysed out to
      21 days of differentiation in stably transfected cell lines. The highest
      expressing cell line was found to qualitatively retain a similar differentiation
      potential to untransfected cells, and to secrete alpha-mannosidase that could
      mediate a reduction in the level of oligosaccharides stored by human alpha
      mannosidosis skin fibroblasts. These results suggest potential for the use of
      this cell line for investigation of a stem cell therapy approach to treat alpha
      mannosidosis.

PMID- 15979033
TI  - A G-to-A transition at the fifth position of intron-32 of the dystrophin gene
      inactivates a splice-donor site both in vivo and in vitro.
AB  - The splicing pattern of pre-mRNA is unpredictable in genes harboring a single
      nucleotide change within the consensus sequence of a splice-donor site. In the
      dystrophin gene, a transition from G to A at the fifth position of intron-32
      (4518+5G > A) has been reported as a polymorphism within the consensus sequence
      or a mutation identified in Duchenne muscular dystrophy (DMD). Here, we report
      both in vivo and in vitro evidence that shows inactivation of the splice-donor
      site caused by this mutation. In one Japanese DMD case, two novel dystrophin
      mRNAs were identified in the patient's lymphocytes, one with a 98 bp deletion of
      the 3' end of exon-32 (dys32-98) and the other with a 28 bp intron retained
      between exons 32 and 33 (dys32 + 28). Genomic sequencing disclosed a single
      nucleotide change from G to A at the fifth position of intron-32 (4518+5G > A).
      To demonstrate in vitro the inactivation of this splice-donor site by this
      nucleotide change, mini-dystrophin genes comprising three exons harboring either
      normal or mutant intron-32 sequences were expressed in HeLa cells, and the
      splicing products were analyzed by reverse-transcription PCR amplification. A
      normal transcript consisting of three exons was obtained from the normal
      construct. From the mutant, we obtained one product containing a 98 bp deletion
      at the 3' end of exon-32, indicating complete inactivation of the native splice
      donor site. Thus, both in vivo and in vitro experiments demonstrate that 4518+5G
      > A causes a splicing error leading to transcript termination; it did not behave
      like a silent polymorphism. Our results indicate that the in vitro splicing
      system is a powerful tool for determining the underlying mechanism of a disease
      causing mutation in a splicing consensus sequence.

PMID- 15979034
TI  - Analysis of methionine synthase reductase polymorphisms for neural tube defects
      risk association.
AB  - Methionine synthase reductase (MTRR) regenerates methylated cobalamin levels from
      the oxidised cob(II)alamin form and in so doing plays a crucial role in
      maintaining the active state of methionine synthase (MTR). MTR is an essential
      enzyme catalyzing the conversion of homocysteine to methionine. Single nucleotide
      polymorphisms (SNPs) within the MTRR gene may potentially compromise MTR activity
      leading to elevated homocysteine levels, a known risk factor for neural tube
      defects (NTDs). We studied the MTRR polymorphisms I22M (66A-->G), S175L (524C-
      >T), and K350R (1049A-->G) as potential NTD risk factors in a large homogeneous
      Irish NTD population. Degree of risk was assessed via case/control comparison,
      log-linear analysis, and transmission disequilibrium testing. No association was
      found between NTDs and I22M in mothers (p = 0.16, OR1.14 [0.95-1.38], n = 447) or
      cases (p = 0.13, OR1.15 [0.96-1.38], n = 470) compared to controls (n = 476). A
      dominant I22M paternal effect was found through case/control comparison and log
      linear modelling (p = 0.019) (goodness-of-fit p=0.91, OR 1.46 [1.10-1.93], n =
      423). No significant NTD association was found with S175L or K350R in cases or
      their parents and no interactions were observed between these polymorphisms and
      the D919G variant of MTR or the A222V variant of 5,10-methylenetetrahydrofolate
      reductase (MTHFR). We also compared the frequencies of I22M, S175L, and K350R in
      African-Americans versus American-Caucasians. The frequencies of I22M and K350R
      differed significantly between the two groups (p = 0.0005 and p = 0.0001,
      respectively). Our findings do not support an important role for these MTRR
      variants in NTDs.

PMID- 15979035
TI  - Molecular studies in Portuguese patients with Smith-Lemli-Opitz syndrome and
      report of three new mutations in DHCR7.
AB  - Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterised
      by craniofacial dysmorphism, mental retardation, multiple congenital anomalies,
      and increased levels of 7-dehydrocholesterol (7-DHC) in body tissues and fluids.
      SLO is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol
      reductase, the last enzyme of cholesterol biosynthesis pathway. In our
      investigation, we screened 682 dysmorphic/mentally retarded Portuguese patients
      for abnormal levels of 7-DHC in blood by UV spectrometry. We identified six
      unrelated patients with SLO (0.87% of total). Mutational analysis of the DHCR7
      gene led to the identification of seven distinct mutations, three of which are
      new (F174S, H301R, and Q98X). The common IVS8-1G > C and T93M variants together
      with the H301R accounted for 70% of the all SLO alleles in our population. Our
      findings contribute to the variegate array of pathological changes in the DHCR7
      gene among different European populations.

PMID- 15979036
TI  - An index case for the attenuated end of the mucopolysaccharidosis type VI
      clinical spectrum.
AB  - Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome, McKusick #253200)
      is a lysosomal storage disorder that is caused by a deficiency in the lysosomal
      exohydrolase N-acetylgalactosamine-4-sulphatase (4-sulphatase, EC 3.1.6.1). We
      report a patient with no obvious clinical signs of MPS VI that has 5% of normal 4
      sulphatase catalytic capacity. This patient represents an index case for the
      attenuated end of the MPS VI clinical spectrum.

PMID- 15979037
TI  - A novel mutation in the PYGM gene in a family with pseudo-dominant transmission
      of McArdle disease.
AB  - A Caucasian family appeared to transmit McArdle disease in an autosomal dominant
      manner and was examined for mutations in the myophosphorylase gene. The
      asymptomatic father was heterozygous for the R49X mutation in exon 1. The
      symptomatic mother was a compound heterozygote for R49X and a novel 2 bp deletion
      in exon 1 causing a frameshift at codon 25 (T25fs). Each of three children
      manifested symptoms of McArdle disease and was either a compound heterozygote for
      these two mutations or homozygous for R49X.

PMID- 15979038
TI  - Genome-based identification of diagnostic molecular markers for human lung
      carcinomas by PLS-DA.
AB  - Partial least squares discriminant analysis (PLS-DA) provides a sound statistical
      basis for the selection of a limited number of gene transcripts most effective in
      discriminating different lung tumoral histotypes. The potentialities of the PLS
      DA approach are pointed out by its ability to identify genes which, according to
      current knowledge, are considered molecular markers for colon cancer diagnostics
      and classification. Indeed application of PLS-DA to in vivo data allowed
      identification of a set of genes able to discriminate primary lung tumours from
      colon metastases.

PMID- 15979039
TI  - Integer linear programming as a tool for constructing trees from quartet data.
AB  - The task of the quartet puzzling problem is to find a best-fitting binary X-tree
      for a finite n-set from confidence values for the 3n4 binary trees with exactly
      four leaves from X, its fitness being measured by the sum of the confidence
      values of all "induced" four-leaves subtrees. We describe a method for finding an
      exact solution of this problem by integer linear programming. Similar procedures
      can also be used for finding, e.g. best-fitting "circular" networks. A crucial
      problem in this context is, of course, how to obtain the input confidence values
      for the quartet trees. We propose to use inner products of rate-matrix diagonals
      calculated for pairs of taxa and present the trees resulting from applying our
      approach to two data sets of up to 36 mitochondrial sequences of mammals
      including an outgroup.

PMID- 15979040
TI  - Borrowing information from relevant microarray studies for sample classification
      using weighted partial least squares.
AB  - With an increasing number of publicly available microarray datasets, it becomes
      attractive to borrow information from other relevant studies to have more
      reliable and powerful analysis of a given dataset. We do not assume that subjects
      in the current study and other relevant studies are drawn from the same
      population as assumed by meta-analysis. In particular, the set of parameters in
      the current study may be different from that of the other studies. We consider
      sample classification based on gene expression profiles in this context. We
      propose two new methods, a weighted partial least squares (WPLS) method and a
      weighted penalized partial least squares (WPPLS) method, to build a classifier by
      a combined use of multiple datasets. The methods can weight the individual
      datasets depending on their relevance to the current study. A more standard
      approach is first to build a classifier using each of the individual datasets,
      then to combine the outputs of the multiple classifiers using a weighted voting.
      Using two quite different datasets on human heart failure, we show first that
      WPLS/WPPLS, by borrowing information from the other dataset, can improve the
      performance of PLS/PPLS built on only a single dataset. Second, WPLS/WPPLS
      performs better than the standard approach of combining multiple classifiers.
      Third, WPPLS can improve over WPLS, just as PPLS does over PLS for a single
      dataset.

PMID- 15979041
TI  - Structural analysis of inhibition mechanisms of aurintricarboxylic acid on SARS
      CoV polymerase and other proteins.
AB  - We recently published experimental results that indicated Aurintricarboxylic Acid
      (ATA) could selectively inhibit SARS-CoV replication inside host cells by greater
      than 1000 times. This inhibition suggested that ATA could be developed as potent
      anti-viral drug. Here, to extend our experimental observation, we have
      incorporated protein structural studies (with positive/negative controls) to
      investigate the potential binding modes/sites of ATA onto RNA-dependent RNA
      polymerase (RdRp) from SARS-CoV and other pathogenic positive-strand RNA-viruses,
      as well as other proteins in SARS-CoV based on the fact that ATA binds to Ca2+
      activated neutral protease (m-calpain), the protein tyrosine phosphatase (PTP)
      and HIV integrase which have existing crystal structures. Eight regions with
      homologous 3D-conformation were derived for 10 proteins of interest. One of the
      region, Rbinding (754-766 in SARS-CoV's RdRp), located in the palm sub-domain
      mainly constituted of anti-parallel beta-strand-turn-beta-strand hairpin
      structures that covers two of the three RdRp catalytic sites (Asp 760, Asp761),
      was also predicted by molecular docking method (based on free energy of binding
      DeltaG) to be important binding motif recognized by ATA. The existence of this
      strictly conserved region that incorporated catalytic residues, coupled with the
      homologous ATA binding pockets and their consistent DeltaG values, suggested
      strongly ATA may be involved in an analogous inhibition mechanism of SARS-COV's
      RdRp in concomitant to the case in m-calpain, PTP and HIV integrase.

PMID- 15979042
TI  - Analyzing functional similarity of protein sequences with discrete wavelet
      transform.
AB  - This paper applies discrete wavelet transform (DWT) with various protein
      substitution models to find functional similarity of proteins with low identity.
      A new metric, 'S' function, based on the DWT is proposed to measure the pair-wise
      similarity. We also develop a segmentation technique, combined with DWT, to
      handle long protein sequences. The results are compared with those using the pair
      wise alignment and PSI-BLAST.

PMID- 15979043
TI  - Latent periodicity of serine-threonine and tyrosine protein kinases and other
      protein families.
AB  - We identified latent periodicity in catalytic domains of approximately 85% of
      annotated serine-threonine and tyrosine protein kinases. Similar results were
      obtained for other 22 protein families and domains. We also designed the method
      of noise decomposition, which is aimed to distinguish between different
      periodicity types of the same period length. The method is to be used in
      conjunction with the method of cyclic profile alignment, and this combination is
      able to reveal structure-related or function-related patterns of latent
      periodicity. Possible origins of the periodic structure of protein kinase active
      sites are discussed. Summarizing, we presume that latent periodicity is the
      common property of many catalytic protein domains.

PMID- 15979044
TI  - GAME: a simple and efficient whole genome alignment method using maximal exact
      match filtering.
AB  - In this paper, we present a simple and efficient whole genome alignment method
      using maximal exact match (MEM). The major problem with the use of MEM anchor is
      that the number of hits in non-homologous regions increases exponentially when
      shorter MEM anchors are used to detect more homologous regions. To deal with this
      problem, we have developed a fast and accurate anchor filtering scheme based on
      simple match extension with minimum percent identity and extension length
      criteria. Due to its simplicity and accuracy, all MEM anchors in a pair of
      genomes can be exhaustively tested and filtered. In addition, by incorporating
      the translation technique, the alignment quality and speed of our genome
      alignment algorithm have been further improved. As a result, our genome alignment
      algorithm, GAME (Genome Alignment by Match Extension), performs competitively
      over existing algorithms and can align large whole genomes, e.g., A. thaliana,
      without the requirement of typical large memory and parallel processors. This is
      shown using an experiment which compares the performance of BLAST, BLASTZ,
      PatternHunter, MUMmer and our algorithm in aligning all 45 pairs of 10 microbial
      genomes. The scalability of our algorithm is shown in another experiment where
      all pairs of five chromosomes in A. thaliana were compared.

PMID- 15979045
TI  - A molecular docking model of SARS-CoV S1 protein in complex with its receptor,
      human ACE2.
AB  - The exact residues within severe acute respiratory syndrome coronavirus (SARS
      CoV) S1 protein and its receptor, human ACE2, involved in their interaction still
      remain largely undetermined. Identification of exact amino acid residues that are
      crucial for the interaction of S1 with ACE2 could provide working hypotheses for
      experimental studies and might be helpful for the development of antiviral
      inhibitor. In this paper, a molecular docking model of SARS-CoV S1 protein in
      complex with human ACE2 was constructed. The interacting residue pairs within
      this complex model and their contact types were also identified. Our model,
      supported by significant biochemical evidence, suggested receptor-binding
      residues were concentrated in two segments of S1 protein. In contrast, the
      interfacial residues in ACE2, though close to each other in tertiary structure,
      were found to be widely scattered in the primary sequence. In particular, the S1
      residue ARG453 and ACE2 residue LYS341 might be the key residues in the complex
      formation.

PMID- 15979046
TI  - Serum cytokine changes in Turkish children infected with Giardia lamblia with and
      without allergy: Effect of metronidazole treatment.
AB  - The present report is a case control study aimed to determine the levels of
      cytokines and other parameters in the sera of allergy-complicated and
      uncomplicated giardiasic children before and after metronidazole treatment. The
      study included a total of 126 subjects; 52 giardiasic children, 34 allergy
      complicated giardiasis (36.9%) and 34 healthy controls, as well as six cases of
      giardiasis simultaneously infected with other parasites or bacterial pathogens.
      Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta,
      soluble IL-2 receptor (sIL-2R), IL-6, IL-8, nitric oxide (NO), and C-reactive
      protein (CRP) were determined. TNF-alpha and sIL-2R levels significantly
      increased in giardiasic cases. IL-1beta, IL-6, IL-8, CRP, and NO levels increased
      only in the cases associated with allergy. All increased variables significantly
      decreased following metronidazole treatment and returned to normal levels.
      Metronidazole-treated patients became 100% parasite free. In conclusion,
      increased TNF-alpha and sIL-2R may be involved in pathogenesis of non-allergic
      giardiasis and probably Th1 type immune response seems to be predominant and this
      response may be protective rather than causative of the disease. Activation of
      the immune system takes place in giardiasis. It is broader and more intense in
      allergy-complicated giardiasis than that of uncomplicated cases, most probably
      due to non-invasive character of G. lamblia. Enhanced IgE production pointed to
      Th2-type immune response and confirms its association with allergy.

PMID- 15979047
TI  - Probing the role of tightly bound phosphoenolpyruvate in Escherichia coli 3-deoxy
      d-manno-octulosonate 8-phosphate synthase catalysis using quantitative time
      resolved electrospray ionization mass spectrometry in the millisecond time range.
AB  - Escherichia coli 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase
      catalyzes the condensation of phosphoenolpyruvate (PEP) and D-arabinose 5
      phosphate (A5P) to produce KDO8P and inorganic phosphate. The enzyme is often
      isolated with varying amounts of tightly bound PEP substrate. To better
      understand the role of tightly bound PEP in E. coli KDO8P synthase catalysis, a
      combination of transient kinetic methodologies including rapid chemical quench
      and mass spectrometry techniques such as time-resolved electrospray ionization
      mass spectrometry (ESI-TOF MS) were used to study the enzyme purified both in the
      PEP-bound state and in the unbound state. Pre-steady state burst and single
      turnover experiments using radiolabeled [1-(14)C] and [(32)P]A5P revealed
      significant kinetic differences between these enzyme preparations. The active
      sites concentrations for the bound and unbound states of the enzyme were almost
      the same (approximately 100%) and the product release for both states of the
      enzyme was rate limiting. However, the rate constant of product formation for the
      PEP-bound enzyme (125 s(-1)) was higher than that of the unbound enzyme (46 s(
      1)). This was further confirmed by single-turnover experiments using radiolabeled
      [(32)P]A5P. Interestingly, when PEP was removed from the PEP-bound enzyme and
      external PEP was added before the kinetic experiments, both the pre-steady state
      burst and the single-turnover kinetic parameters were similar to those of the
      enzyme purified in the unbound state. The rate constants of product formation
      were determined as 44 s(-1) (burst experiment) and 48 s(-1) (single-turnover
      experiment). The reaction kinetics of the E. coli KDO8P synthase was also
      followed by time-resolved ESI mass spectrometry. To validate the suitability of
      this technique for conducting enzyme kinetics, the standard reaction of p
      nitrophenyl acetate hydrolysis by chymotrypsin was analyzed by stopped-flow and
      time-resolved ESI-TOF MS. The rate constant of p-nitrophenol formation followed
      by stopped-flow spectrophotometry matched perfectly the rate constant of acetyl
      chymotrypsin intermediate formation followed by time-resolved ESI-TOF MS (0.1 s(
      1)). The catalytic properties of the PEP-bound and unbound states of the E. coli
      KDO8P synthase were then studied on a millisecond time scale. The changes in the
      intensity of E*PEP, E*KDO8P, and E*intermediate complexes as a function of time
      were quantified and the reaction kinetics were modeled using KinTekSim simulation
      software. An analysis of the reaction kinetics established the kinetic competence
      of the intermediate based upon the rate constants for substrate decay and product
      formation. The ability of time-resolved ESI-TOF MS to detect and monitor the
      kinetics for the reaction intermediate constitutes a significant advantage over
      the traditional rapid chemical quench technique. For all three states of the
      enzyme (PEP-bound, unbound, and PEP removed from the PEP-bound state) the rate
      constants obtained by time-resolved ESI-TOF MS matched the pre-steady state rates
      determined by rapid chemical quench. A comparison of reaction time courses for
      each state of the enzyme revealed that, in the case of PEP-bound enzyme, the
      enzymatic reaction reached completion faster than that for the unbound state. In
      summary, these studies led to the conclusion that bound PEP has an important role
      in catalysis, maintaining the enzyme in a conformational state optimal for
      catalytic activity, and established the kinetic competence of the reaction
      intermediate. This technique has broad applicability for the kinetic analysis of
      any enzyme system where the substrates, products, or intermediates are eluding
      the common detection techniques or as a method alternative to the widely used
      radioactivity assays.

PMID- 15979048
TI  - [Anatomical substratum of primary hyperaldosteronism: from the difficulties of
      the diagnosis to the surgical management].

PMID- 15979049
TI  - Endocrine pancreatic tissue plasticity in obese humans is associated with
      cytoplasmic expression of PBX-1 in pancreatic ductal cells.
AB  - In vivo lineage tracing experiments in mice have recently cast doubt on the
      potential islet neogenesis from ductal precursors in adult mammals. We examined,
      in human obesity, a model for pancreatic endocrine tissue plasticity, the gene
      and protein expression of PBX-1-a transcription factor expressed in regenerating
      rat ductules and potentially implicated in the pancreatic development, alone or
      in association with PDX-1. When comparing gene expression, by quantitative real
      time RT-PCR, in pancreatic exocrine tissue from obese non-diabetic subjects with
      increased islet mass, we found that Pbx-1 and Pdx-1 were up-regulated (5.9+/-1.2
      and 2.4+/-0.6 versus non-obese). Immunohistochemistry confirmed PBX-1 over
      expression and its cytoplasmic sequestration in ductal cells of obese subjects,
      associated with pronounced islet neogenesis (cytokeratin 19/chromogranin A double
      labeling). cDNA microarray analysis also showed up-regulation of other genes
      implicated in islet regeneration, including betacellulin, laminin, TGFa, NeuroD1,
      Pax6, substantiating the role of the islet neogenesis pathway in human obesity.

PMID- 15979050
TI  - Induction of apoptosis and endothelin-1 secretion in primary human lung
      endothelial cells by HIV-1 gp120 proteins.
AB  - Pulmonary hypertension associated with human immunodeficiency virus (HIV)
      infection also involves injury to the lung endothelium. However, the pathogenesis
      of HIV-induced pulmonary hypertension is not known; we hypothesized that HIV or
      secreted viral proteins could play a role in vascular injury and the increased
      frequency of pulmonary hypertension observed in HIV-infected patients. Here, we
      report that exposure of HIV-1 gp120 proteins to primary human lung microvascular
      endothelial cells causes apoptosis, as assessed by TUNEL assay, Annexin-V
      staining, and DNA laddering. Using ribonuclease protection assay and Western
      blotting we find that gp120-induced apoptosis of lung endothelial cells involves
      a down-regulation in Bcl-xl mRNA and proteins. In addition, gp120 significantly
      increases secretion of the potent vasoconstrictor endothelin-1 by human lung
      endothelial cells. These data suggest that secreted HIV gp120 proteins induce
      lung endothelial cell injury and could contribute to the development of HIV
      associated pulmonary hypertension.

PMID- 15979051
TI  - Comparison of MukB homodimer versus MukBEF complex molecular architectures by
      electron microscopy reveals a higher-order multimerization.
AB  - The complex of MukF, MukE, and MukB proteins participates in organization of
      sister chromosomes and partitioning into both daughter cells in Escherichia coli.
      We purified the MukB homodimer and the MukBEF complex and analyzed them by
      electron microscopy to compare both structures. A MukB homodimer shows a long rod
      hinge-rod v-shape with small globular domains at both ends. The MukBEF complex
      shows a similar structure having larger globular domains than those of the MukB
      homodimer. These results suggest that MukF and MukE bind to the globular domains
      of a MukB homodimer. The globular domains of the MukBEF complex frequently
      associate with each other in an intramolecular fashion, forming a ring. In
      addition, MukBEF complex molecules tend to form multimers by the end-to-end
      joining with other MukBEF molecules in an intermolecular fashion, resulting in
      fibers and rosette-form structures in the absence of ATP and DNA in vitro.

PMID- 15979052
TI  - The linkage between O-specific caryan and core region in the lipopolysaccharide
      of Burkholderia caryophylli is furnished by a primer monosaccharide.
AB  - From the lipopolysaccharide (LPS) fraction of the plant-pathogenic bacterium
      Burkholderia caryophylli, the linkage between O-specific caryan and core region
      was characterised. The LPS fraction was first treated with 48% aqueous HF at 4
      degrees C and successively with 1% acetic acid at 100 degrees C. A main
      oligosaccharide representing the carbohydrate backbone of the core region and a
      portion of the caryan (three unit of caryose) was isolated by high-performance
      anion-exchange chromatography. Compositional and methylation analyses, matrix
      assisted laser desorption/ionisation mass spectrometry and 2D NMR spectroscopy
      identified the structure: [carbohydrate structure: see text]. The above residues
      are alpha-linked pyranose rings, if not stated otherwise. Hep is L-glycero-D
      manno-heptose, Car is 4,8-cyclo-3,9-dideoxy-L-erythro-D-ido-nonose and Kdo is 3
      deoxy-D-manno-oct-2-ulosonic acid. This finding indicates that QuiNAc residue is
      the primer monosaccharide, which connects the core oligosaccharide to caryan O
      chain.

PMID- 15979053
TI  - Synthesis of 2,3:4,6-di-O-isopropylidene-D-allopyranose from D-glucose.
AB  - 2,3:4,6-Di-O-isopropylidene-d-allopyranose can be conveniently prepared from d
      glucose via a synthetic sequence, which includes Mitsunobu inversion at O-3, di-O
      isopropylidenation of phenyl-1-thio-d-alloside and anomeric deprotection on
      treatment with NBS/CaCO3.

PMID- 15979054
TI  - Preparation and antimicrobial activity of hydroxypropyl chitosan.
AB  - Water-soluble hydroxypropyl chitosan (HPCS) derivatives with different degrees of
      substitution (DS) and weight-average molecular weight (Mw) were synthesized from
      chitosan and propylene epoxide under basic conditions. Their structure was
      characterized by IR spectroscopy, NMR spectroscopy, and elemental analysis, which
      showed that both the OH groups at C-6 and C-3 and the NH2 group of chitosan were
      alkylated. The DS value of HPCS ranged from 1.5 to 3.1 and the Mw was between
      2.1x10(4) and 9.2x10(4). In vitro antimicrobial activities of the HPCS
      derivatives were evaluated by the Kirby-Bauer disc diffusion method and the
      macrotube dilution broth method. The HPCS derivatives exhibited no inhibitory
      effect on two bacterial strains (Escherichia coli and Staphylococcus aureus);
      however, some inhibitory effect was found against four of the six pathogenic
      fruit fungi investigated. Some derivatives (HPCS1, HPCS2, HPCS3, HPCS3-1, and
      HPCS4) were effective against C. diplodiella and F. oxysporum. HPCS3-1 is the
      most effective one with MIC values of 5.0, 0.31, 0.31, and 0.16mg/mL against A.
      mali, C. diplodiella, F. oxysporum, and P. piricola, respectively. Antifungal
      effects were also observed for HPCS2 and HPCS3-1 against A. mali, as well as
      HPCS3 and HPCS3-1 against P. piricola. The results suggest that relatively lower
      DS and higher Mw value enhances the antifungal activity of HPCS derivatives.

PMID- 15979055
TI  - New, emerging roles for cardiac connexins. Mitochondrial Cx43 raises new
      questions.

PMID- 15979056
TI  - Role of the JNK pathway in thrombin-induced ICAM-1 expression in endothelial
      cells.
AB  - OBJECTIVE: Thrombin induces leukocyte adherence to endothelial cells via
      increased expression of intercellular adhesion molecule-1 (ICAM-1). Although ICAM
      1 expression is regulated by NF-kappaB, recent studies have suggested that
      additional signaling mechanisms may also be involved. The goal of this study was
      to determine whether mitogen-activated protein (MAP) kinases, including
      extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase
      (JNK), and p38 MAP kinase (p38), mediate thrombin-induced ICAM-1 expression in
      endothelial cells. METHODS: Western blot analysis using anti-ICAM-1 antibody and
      luciferase assays were performed in cultured endothelial cells after addition of
      signal transduction inhibitors or transfection of various gene constructs. JNK
      kinase activity was determined by a kinase assay using c-Jun as a substrate or by
      Western blot analysis with anti-phospho-JNK antibody. RESULTS: Treatment of
      endothelial cells with the JNK-specific inhibitors, SP600125 or JNK inhibitory
      peptide 1 (JNKI1), resulted in a significant decrease in thrombin-induced ICAM-1
      expression as demonstrated by Western blot analysis (67 +/- 3% and 72 +/- 7%,
      respectively). In contrast, inhibitors of MEK and p38 had only minimal effect.
      The combination of SP600125 and the NF-kappaB inhibitor, BAY11-7082, resulted in
      complete inhibition of thrombin-induced ICAM-1 expression. The Galpha(q)
      inhibitor, YM-254890, inhibited thrombin-induced JNK activation and ICAM-1
      expression. Dominant-negative Ras and Rac1, but not Rho, inhibited thrombin
      induced JNK activation and ICAM-1 promoter activity. Finally, thrombin-induced
      JNK activation and ICAM-1 promoter activity were inhibited by betaARK1ct (a
      Gbetagamma subunit scavenger) and Csk. CONCLUSIONS: These data suggest that, in
      concert with NF-kappaB, JNK regulates thrombin-induced ICAM-1 expression by a
      mechanism that is dependent on Galpha(q), Gbetagamma, Ras, Rac1 and the Src
      kinase family.

PMID- 15979057
TI  - The patient U wave.

PMID- 15979058
TI  - Mesothelial cell transplantation in the infarct scar induces neovascularization
      and improves heart function.
AB  - OBJECTIVES: Cell transplantation and associated neovascularization in vivo may be
      beneficial in ischemic disease. We hypothesized that transplanted mesothelial
      cells (MCs) could improve neovascularization in the post-myocardial infarct scar
      in rats. METHODS: Myocardial infarction was created by left coronary artery
      ligation in Lewis rats. After 3 weeks, surviving rats with left ventricular (LV)
      ejection fraction (EF) <50% were randomized into 2 groups which received, via
      injection into the infarct scar, either syngeneic rat peritoneal MCs
      (transplanted group) or vehicle alone (control group). Rats were followed-up
      echocardiographically for 4 weeks. Before transplantation, cells were transfected
      in vitro or labeled by a fluorescent dye for subsequent tracking in vivo.
      Transplanted cells and neovascularization were assessed histologically in the
      infarct scar by immunostaining or intravenous FITC-dextran injection prior to
      sacrifice, from 1 to 30 days post-transplantation. RESULTS: Among other pro
      angiogenic chemokines, cultured MCs released stromal cell-derived factor (SDF
      1alpha) (15.9 +/- 1.8 microg/mg protein) in vitro. At 1 month, some transplanted
      MCs were visualized (surviving or proliferating) in the LV scar and were
      incorporated in new vessels. The transplanted rats presented an increased
      vascular density in the scar, improved LV-EF (44.0 +/- 8.6% vs. 24.0 +/- 4.5%, p
      < 0.01) with decreased LV end-diastolic diameter (9.6 +/- 0.6 vs. 11.1 +/- 0.6
      mm, p < 0.01) and volume (0.47 +/- 0.1 vs. 0.63+/-0.1 ml, p < 0.01) vs. controls.
      One week post-transplantation, higher levels of SDF-1alpha were extracted from LV
      peri-infarct tissue (32.3 +/- 5.8 vs. 22.6 +/- 3.1 pg/mg protein in controls, p <
      0.01). CONCLUSIONS: Since autologous MCs can be obtained easily and cultured in
      large quantities, MC transplantation may represent a new angiogenic strategy in
      the prevention of ischemic remodeling.

PMID- 15979059
TI  - Quantitative evaluation of SNT in biological material is currently hindered by
      many methodological problems.

PMID- 15979060
TI  - Determination of total and free plasma carnitine concentrations on the Dade
      Behring Dimension RxL: integrated chemistry system.
AB  - BACKGROUND: L-carnitine is a naturally occurring quaternary ammonium compound
      present in all mammalian species. Its major function is to facilitate the passage
      of long-chain fatty acids through the mitochondrial membrane for subsequent beta
      oxidation and ketone synthesis. Clinical interest in carnitine disorders relates
      particularly to possible deficiency states that may result in a phenotypic
      spectrum that includes cardiomyopathy, skeletal myopathy, hypoglycemia and
      hyperammonemia. The objective of this study was to develop a method on the Dade
      Behring Dimension RxL analyzer for measuring free and total carnitine levels in
      plasma. METHODS: Plasma samples were deproteinized by ultrafiltration to remove
      interference by endogenous thiols. Filtrates were measured directly on the RxL
      for free carnitine or after alkaline hydrolysis for total carnitine by an
      endpoint enzymatic assay that uses carnitine acetyltransferase. RESULTS: Within
      run imprecision was <5% at high and low levels for both free and total carnitine
      while between-day imprecision was <15%. Recovery of free carnitine from spiked
      plasma >90%. The method was linear between 5.0 and 150.0 micromol/l and the limit
      of quantification was 5.0 micromol/l. Comparison of our method with another
      automated procedure developed on the Hitachi 917 system using Deming regression
      analysis resulted in the following equations: Dimension=1.034(Hitachi)-7.44 for
      total carnitine (r=0.955) and Dimension=0.805(Hitachi)+1.96 for free carnitine
      (r=0.951), respectively. CONCLUSIONS: Our method is suitable for analyzer
      platforms where the level of imprecision is lower and the throughput is higher
      than manual methods. It also avoids the use of radioisotopes and is appropriate
      in labs where access to reference methods such as tandem mass spectrometry and
      HPLC is limited or unavailable.

PMID- 15979061
TI  - Serum non-transferrin bound iron in hemodialysis patients not receiving
      intravenous iron.
AB  - BACKGROUND: Non-transferrin bound iron (NTBI) has been found to be raised in end
      stage renal disease (ESRD) patients on hemodialysis (HD) receiving intravenous
      (IV) iron. Such NTBI is proposed to cause oxidative damage to biomolecules.
      METHOD: NTBI, both ferrous (Fe(+2)) and ferric (Fe(+3)) forms, serum ferritin,
      protein thiols and lipid hydroperoxides were estimated by spectrophotometric and
      electrochemiluminescence immunoassay methods in patients with chronic renal
      failure (CRF), patients with ESRD on HD not receiving IV iron, and in normal
      controls. RESULTS: NTBI (Fe(+2)) in HD patients not receiving IV iron was higher
      than in normal controls. NTBI (Fe(+3)) was significantly higher in HD patients
      not on IV iron therapy than in CRF and normal controls. There was no significant
      increase in NTBI in CRF patients when compared to normal controls. Serum ferritin
      was higher in HD patients compared to CRF and normal controls. There was a
      significant increase in lipid hydroperoxides and protein thiols in HD patients
      and CRF patients when compared to normal controls. The NTBI did not correlate
      with serum ferritin and oxidative markers. CONCLUSION: The source of NTBI in
      hemodialysis is not only IV iron therapy but also the hemodialysis procedure per
      se. It may be due to microhemolysis during hemodialysis. The NTBI is however
      found to be catalytically inactive.

PMID- 15979062
TI  - Serum alcohol dehydrogenase levels in patients with mental disorders.
AB  - Alcohol dehydrogenase (ADH) was assessed in 81 patients admitted to hospital for
      treatment for alcohol dependence with or without liver cirrhosis, 20 patients
      with bipolar disorder treated with lithium carbonate and 41 patients with various
      mental disorders treated with psychopharmacologic agents. Testing the hypothesis
      of the arithmetic mean showed that in alcohol dependents the arithmetic mean of
      ADH activity (12.19 nkat/l+/-5.61) differs significantly from that in healthy
      subjects (4.45 nkat/l+/-2.31) and in the group with ethanol poisoning (6.24
      nkat/l+/-3.65) there is none. In the group with bipolar disorder, treated with
      lithium (7.39 nkat/l+/-3.11) and, in the group of patients treated with
      psychiatric drugs because of various mental disorders (7.79 nkat/l+/-8.51), the
      differences are statistically significant. In our opinion, assessing ADH activity
      in the sera of alcohol dependents could be an additional marker advantageous to
      the diagnostics, course and monitoring of therapy in such patients. In the groups
      of patients with mental disorders treated with psychotropic drugs, the increased
      ADH activity was found to be a more sensitive marker for the detection of drug
      hepatotoxicity.

PMID- 15979063
TI  - Cholesteryl ester detection in a human urothelial carcinoma.

PMID- 15979064
TI  - Cryoprotectant equilibration in tissues.
AB  - The first step in the cryopreservation of cells or tissues is often the movement
      of a permeating cryoprotectant into the cells or tissues from the solution into
      which they have been placed. The cryoprotectant enters the cells or tissues by
      thermodynamic equilibration with the surroundings. In the reverse case,
      thermodynamic equilibration also drives the removal of permeating cryoprotectants
      by a dilution solution at the end of the preservation process when the cells or
      tissues are being readied for use. There have been reports of tissues having
      equilibrium cryoprotectant concentrations lower than that of the surrounding
      carrier solution. For various tissues, the equilibrium concentration of
      cryoprotectant inside the tissue is either equal to, or lower than the
      cryoprotectant concentration of the surrounding solution. A simple thermodynamic
      treatment of the solution-tissue equilibrium shows that an equilibrium
      concentration difference can exist between a tissue and the surrounding solution
      if a pressure difference can be maintained.

PMID- 15979065
TI  - Src64 is involved in fusome development and karyosome formation during Drosophila
      oogenesis.
AB  - Src family tyrosine kinases respond to a variety of signals by regulating the
      organization of the actin cytoskeleton. Here, we show that during early oogenesis
      Src64 mutations lead to uneven accumulation of cortical actin, defects in fusome
      formation, mislocalization of septins, defective transport of Orb protein into
      the oocyte, and possible defects in cell division. Similar mutant phenotypes
      suggest that Src64, the Tec29 tyrosine kinase, and the actin crosslinking protein
      Kelch act together to regulate actin crosslinking, much as they do later during
      ring canal growth. Condensation of the oocyte chromatin into a compact karyosome
      is also defective in Src64, Tec29, and kelch mutants and in mutants for spire and
      chickadee (profilin), genes that regulate actin polymerization. These data, along
      with changes in G-actin accumulation in the oocyte nucleus, suggest that Src64 is
      involved in a nuclear actin function during karyosome condensation. Our results
      indicate that Src64 regulates actin dynamics at multiple stages of oogenesis.

PMID- 15979066
TI  - Relationship of serum levels of individual PCB, dioxin, and furan congeners and
      DDE with Great Lakes sport-caught fish consumption.
AB  - Great Lakes (GL) sport fish consumption is a potential route of exposure for
      environmentally persistent organochlorine contaminants, which may have human
      health effects. In this report, relationships are explored among individual
      congeners in a large cohort of frequent and infrequent GL sport fish consumers.
      Blood samples were obtained in 1993-1995 and analyzed for 1,1-bis(4-chlorophenyl)
      2,2-dichloroethene (DDE) and for 62 noncoplanar polychlorinated biphenyls (PCBs),
      4 coplanar PCBs, 8 polychlorinated dibenzo-p-dioxin (dioxin), and10 dibenzofuran
      (furan) congeners. All GL fish eaters and referents had detectable levels of DDE,
      total noncoplanar PCBs, total coplanar PCBs, total dioxins, and total furans.
      Noncoplanar PCBs were higher in GL sport fish consumers than in a referent
      population from the same geographic area, were associated with GL sport-caught
      fish (GLSCF) consumption, and varied significantly by Great Lake. DDE, lower
      chlorinated dioxin and furan toxic equivalents (TEQs), and coplanar PCB TEQs were
      positively associated with noncoplanar PCBs but were not associated with GL sport
      fish consumption independent of PCB level. Highly chlorinated dioxin and furan
      congener TEQs were not significantly associated with noncoplanar PCBs or GL sport
      fish consumption, suggesting that participants were acquiring some of these TEQs
      from a source other than GLSCF. In epidemiologic studies, it may be important to
      include populations with higher organochlorine exposures as well as background
      exposures and to consider the effects of individual congeners or mixtures of
      congeners on health outcomes.

PMID- 15979067
TI  - The cell surface protein coxsackie- and adenovirus receptor (CAR) directly
      associates with the Ligand-of-Numb Protein-X2 (LNX2).
AB  - The coxsackievirus and adenovirus receptor (CAR) is a cell surface protein that
      is proposed to be involved in cell-cell adhesion. Based on a yeast two-hybrid
      screen, co-immunoprecipitation and binding experiments, the intracellular tail of
      CAR was found to interact both in vivo and in vitro with the Ligand-of-Numb
      Protein-X2 (LNX2). The interacting domains between the two proteins were
      identified by truncation analyses and affinity chromatography. CAR and LNX2
      protein expression in embryonic mouse tissues was analyzed by
      immunohistochemistry. The results suggest that CAR is a partner in a protein
      complex organized at specific subcellular sites by LNX2.

PMID- 15979068
TI  - Differential effects of amphiregulin and TGF-alpha on the morphology of MDCK
      cells.
AB  - Although both amphiregulin and TGF-alpha are known to exert their effects through
      the EGF receptor, we find that concentrations of recombinant human amphiregulin
      and TGF-alpha that are equipotent in EGF receptor activation and mitogenesis
      exhibit markedly different effects on MDCK cell morphology. Amphiregulin induces
      a spindle-like morphology that is associated with a redistribution of E-cadherin
      from a Triton-insoluble to Triton-soluble pool. TGF-alpha does not affect
      epithelial morphology nor does it affect the distribution of the Triton-soluble
      or -insoluble pool of E-cadherin. The effects of amphiregulin on E-cadherin are
      associated with actin rearrangement. The morphological and biochemical effects of
      amphiregulin are prevented by EGF receptor blockade but require Src-family kinase
      activity and MAPK signaling. These results identify an action of amphiregulin
      that is distinct from TGF-alpha that may contribute to amphiregulin's
      participation in the pathogenesis of inflammatory disorders like psoriasis and
      cancer.

PMID- 15979069
TI  - Externalization and recognition by macrophages of large subunit of eukaryotic
      translation initiation factor 3 in apoptotic cells.
AB  - We previously isolated a monoclonal antibody named PH2 that inhibits
      phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages. We
      report here the identification of the cognate antigen. A protein bound by PH2 in
      Western blotting was identified as the 170-kDa subunit of eukaryotic translation
      initiation factor 3 (eIF3 p170/eIF3a). When eIF3a was expressed in a culture cell
      line as a protein fused to green fluorescence protein, the fusion protein was
      detected at the cell surface only after the induction of apoptosis. The same
      phenomenon was seen when the localization of endogenous eIF3a was determined
      using anti-eIF3a antibody, and eIF3a seemed to be partially degraded during
      apoptosis. Furthermore, bacterially expressed N-terminal half of eIF3a fused to
      glutathione S-transferase bound to the surface of macrophages and inhibited
      phagocytosis of apoptotic cells by macrophages when it was added to phagocytosis
      reactions. These results collectively suggest that eIF3a translocates to the cell
      surface upon apoptosis, probably after partial degradation, and bridges apoptotic
      cells and macrophages to enhance phagocytosis.

PMID- 15979070
TI  - Effect of age on outflow resistance washout during anterior chamber perfusion in
      rhesus and cynomolgus monkeys.
AB  - When aqueous humour outflow resistance is measured by two-level constant pressure
      perfusion in non-human primate eyes, a progressive decrease in outflow
      resistance, known as the 'washout effect' occurs with time. The effect of age on
      total outflow resistance washout (the reciprocal of outflow facility (OF)) was
      determined in rhesus and cynomolgus monkeys. In cynomolgus monkeys, the effect of
      time between exchange of the anterior chamber (AC) contents and post-exchange OF
      measurements on outflow resistance was also examined. Total OF was determined at
      baseline in one eye of 35 rhesus monkeys aged 4-29 yrs, and in 27 cynomolgus
      monkeys, aged 3-17 yrs, at baseline and after 10 min AC exchange with 1 or 2 ml
      Barany's perfusand or in Barany's containing 0.01-1% dimethyl sulfoxide (DMSO) or
      Tris base. Resistance washout did not differ with age at baseline in rhesus or
      cynomolgus monkeys. Similarly, no changes were found when comparing post-exchange
      resistance washout vs. age in cynomolgus monkeys that had undergone AC exchange
      with Barany's perfusand only or Barany's containing 0.01-1% DMSO or Tris base.
      Rate of resistance washout decreased with increased length of time between
      exchange of the AC contents and post-exchange outflow facility readings (
      0.0004+/-0.0092 mmHg min(-1) microl(-1) yr(-1); p = 0.016). Several explanations
      for these findings are plausible.

PMID- 15979071
TI  - Measurement of mouse intraocular pressure with the Tono-Pen.

PMID- 15979072
TI  - The evidence for nitric oxide synthase immunopositivity in the monosynaptic Ia
      motoneuron pathway of the dog.
AB  - In this study, nitric oxide synthase immunohistochemistry supported by
      nicotinamide adenine dinucleotide phosphate diaphorase histochemistry was used to
      demonstrate the nitric oxide synthase immunoreactivity in the monosynaptic Ia
      motoneuron pathway exemplified by structural components of the afferent limb of
      the soleus H-reflex in the dog. A noticeable number of medium-sized intensely
      nitric oxide synthase immunoreactive somata (1000-2000 microm(2) square area) and
      large intraganglionic nitric oxide synthase immunoreactive fibers, presumed to be
      Ia axons, was found in the L7 and S1 dorsal root ganglia. The existence of nitric
      oxide synthase immunoreactive fibers (6-8 microm in diameter, not counting the
      myelin sheath) was confirmed in L7 and S1 dorsal roots and in the medial bundle
      of both dorsal roots before entering the dorsal root entry zone. By virtue of the
      funicular organization of nitric oxide synthase immunoreactive fibers in the
      dorsal funiculus, the largest nitric oxide synthase immunoreactive fibers
      represent stem Ia axons located in the deep portion of the dorsal funiculus close
      to the dorsomedial margin of the dorsal horn. Upon entering the gray matter of L7
      and S1 segments and passing through the medial half of the dorsal horn, tapered
      nitric oxide synthase immunoreactive collaterals of the stem Ia fibers pass
      through the deep layers of the dorsal horn and intermediate zone, and terminate
      in the group of homonymous motoneurons in L7 and S1 segments innervating the
      gastrocnemius-soleus muscles. Terminal fibers issued in the ventral horn
      intensely nitric oxide synthase immunoreactive terminals with long axis ranging
      from 0.7 to >or=15.1 microm presumed to be Ia bNOS-IR boutons. This finding is
      unique in that it focuses directly on nitric oxide synthase immunopositivity in
      the signalling transmitted by proprioceptive Ia fibers. Nitric oxide synthase
      immunoreactive boutons were found in the neuropil of Clarke's column of L4
      segment, varying greatly in size from 0.7 to >or=15.1 microm in length x 0.7 to
      4.8 microm wide. Subsequent to identification of the afferent nitric oxide
      synthase immunoreactive limb of the monosynaptic Ia-motoneuron pathway on control
      sections, intramuscular injections of the retrograde tracer Fluorogold into the
      gastrocnemius-soleus muscles, combined with nitric oxide synthase
      immunohistochemistry of L7 and S1 dorsal root ganglia, confirmed the existence of
      a number of medium-sized nitric oxide synthase immunoreactive somata (1000-2000
      microm(2) square area) in the dorsolateral part of both dorsal root ganglia,
      presumed to be proprioceptive Ia neurons. Concurrently, large nitric oxide
      synthase immunoreactive fibers were detected at the input and output side of both
      dorsal root ganglia. S1 and S2 dorsal rhizotomy caused a marked depletion of
      nitric oxide synthase immunoreactivity in the medial bundle of S1 and S2 dorsal
      roots and in the dorsal funiculus of S1, S2 and lower lumbar segments. In
      addition, anterograde degeneration of large nitric oxide synthase immunoreactive
      Ia fibers in the dorsal funiculus of L7-S2 segments produces direct evidence that
      the afferent limb of the soleus H-reflex is nitric oxide synthase immunoreactive
      and presents new immunohistochemical characteristics of the monosynaptic Ia
      motoneuron pathway, unseparably coupled with the performance of the stretch
      reflex.

PMID- 15979073
TI  - Winning fights elevates testosterone levels in California mice and enhances
      future ability to win fights.
AB  - The 'winner effect' has been studied in a variety of species, but only rarely in
      mammals. We compared effects of winning three, two, one, or zero resident
      intruder encounters on the likelihood of winning a subsequent aggressive
      encounter in the California mouse (Peromyscus californicus). During the training
      phase, we ensured that resident males won all encounters by staging contests with
      mildly sedated, smaller intruders. During the test phase, the resident male
      encountered an unfamiliar, more evenly matched intruder that had experience
      winning an encounter and was larger than the resident. Testosterone (T) plasma
      levels significantly increased after the final test when they had experienced two
      prior winning encounters, and the probability of winning a future encounter
      increased significantly after three prior wins independent of intrinsic fighting
      ability. We hypothesize a 'winner-challenge' effect in which increased T levels
      serve to reinforce the winner effect in male California mice.

PMID- 15979074
TI  - Orthopaedic trauma: establishment of an outcomes registry to evaluate and monitor
      treatment effectiveness.

PMID- 15979075
TI  - The ethics and practical importance of defining, distinguishing and disclosing
      nursing errors: a discussion paper.
AB  - Nurses globally are required and expected to report nursing errors. As is clearly
      demonstrated in the international literature, fulfilling this requirement is not,
      however, without risks. In this discussion paper, the notion of 'nursing error',
      the practical and moral importance of defining, distinguishing and disclosing
      nursing errors and how a distinct definition of 'nursing error' fits with the new
      'system approach' to human-error management in health care are critiqued. Drawing
      on international literature and two key case exemplars from the USA and
      Australia, arguments are advanced to support the view that although it is 'right'
      for nurses to report nursing errors, it will be very difficult for them to do so
      unless a non-punitive approach to nursing-error management is adopted.

PMID- 15979076
TI  - Critical care nurses' beliefs about the discharge planning process: a
      questionnaire survey.
AB  - AIM: To report on the beliefs of critical care nurses with regard to the
      discharge planning process, in Victoria, Australia. METHODS: An exploratory
      descriptive design was used. A total of 502 Victorian critical care nurses were
      approached to take part in the study. A total of 218 eligible participants
      completed the survey, which represented a net response rate of 43.4%. The data
      were analysed using descriptive statistics. RESULTS: The current discharge
      planning processes are ad hoc and influenced by patient acuity. Critical care
      nurses believe that workload issues, unplanned discharges and inadequate
      communication contribute to difficulties implementing the discharge plan.

PMID- 15979077
TI  - Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic
      rabbits.
AB  - A numerous studies suggest that Vitamin E has a preventive role in
      atherosclerosis, although the mechanism of action still remains unclear. CD36, a
      member of the scavenger receptor family is centrally involved in the uptake of
      oxidized low density proteins (oxLDLs) from bloodstream. During the
      atherosclerotic process, the lipid cargo of oxLDL accumulates in macrophages and
      smooth muscle cells, inducing their pathological conversion to foam cells. In the
      present study, we investigate the role of Vitamin E on CD36 expression in an in
      vivo model. Atherosclerosis was induced by a 2% cholesterol containing Vitamin E
      poor diet. Three groups of six rabbits each were studied. The first group
      (control) was fed on Vitamin E poor diet. The second group was fed with Vitamin E
      poor diet containing 2% cholesterol and the rabbits in the third group were fed
      with Vitamin E poor diet containing 2% cholesterol and received injections of 50
      mg/kg of Vitamin E i.m. After 4 weeks, aortas were removed and analysed by light
      microscopy for atherosclerotic lesions. Aortic samples were analysed for CD36
      mRNA expression. The aortas of cholesterol-fed rabbits showed typical
      atherosclerotic lesions, detected by macroscopic and microscopic examination, and
      exhibited an increase in CD36 mRNA expression. Vitamin E fully prevented
      cholesterol induced atherosclerotic lesions and the induction of CD36 mRNA
      expression. The effects observed at the level of CD36 scavenger receptor
      expression in vivo suggest an involvement of reduced foam cell formation in the
      protective effect of Vitamin E against atherosclerosis.

PMID- 15979078
TI  - Simultaneous expression of apolipoprotein B mRNA editing enzyme and scavenger
      receptor BI mediated by a therapeutic gene expression system.
AB  - Cardiovascular diseases are often accompanied by elevated LDL particles and
      endothelial dysfunction. We have examined the possibility of concurrently
      reducing LDL levels and modulating endothelial function using a single helper
      dependent adenovirus vector system to simultaneously express the apolipoprotein B
      mRNA editing enzyme (Apobec1) and the scavenger receptor, class B, type I (SR-BI)
      genes under the control of separate promoters (designated HD-C2). Apobec1 edits
      apoB mRNA at nucleotide C-6666 to produce truncated apoB48 and is normally
      expressed in small intestine only. SR-BI is a receptor for multiple ligands with
      distinct tissue-specific functions. Expression of Apobec1 in HepG2 cells resulted
      in apoB mRNA editing, leading to decreased apoB100 abundance (to 6% of control)
      and the appearance of apoB48. Editing of apoB mRNA in HepG2 cells resulted in
      decline in apoB mRNA levels of 50%. This was probably the result of nonsense
      mediated decay of edited message, since over-expression of Apobec1 increased
      neither Apobec1 complementary factor (ACF) mRNA nor protein abundance. Over
      expression of SR-BI in human endothelial cells activated endothelial nitric oxide
      synthase (eNOS) activity by phosphorylation of eNOS at residue Ser-1177 in the
      presence of HDL, leading to increased production of the anti-atherogenic molecule
      nitric oxide (NO). Taken together, this study demonstrates that using one vector
      delivery system to express two genes in two different cell types results in the
      cell-specific beneficial effects of decreasing apoB100 production and increasing
      eNOS activities. This combined gene expression approach may provide an improved
      therapeutic strategy by targeting multiple sites in the mechanism of
      cardiovascular injury.

PMID- 15979079
TI  - The monocytic lineage specific soluble CD163 is a plasma marker of coronary
      atherosclerosis.
AB  - BACKGROUND: CD163 is a monocyte-macrophage lineage specific scavenger receptor
      that mediates the uptake and clearance of haptoglobin-haemoglobin complexes, and
      soluble CD163 (sCD163) is also present in plasma. As atherosclerosis involves
      infiltration by monocyte-derived macrophages, we investigated whether sCD163 may
      act as a marker of coronary atherosclerosis (CAD). METHODS AND RESULTS: Clinical
      features were identified and plasma was collected from 147 consecutive patients
      presenting for coronary angiography. Patients were classified as having CAD+, or
      being free of CAD- haemodynamically significant (>50% luminal diameter) coronary
      stenoses in one or more major coronary arteries (1, 2 or 3 vessel disease), and
      sCD163 concentration was measured by ELISA. Plasma sCD163 was non-parametrically
      distributed, being significantly higher in CAD+ patients (median 2.47 mg/L, 25th
      75th percentile, 1.79-3.5mg/L) than in CAD- patients (2.09, 1.31-2.72 mg/L)
      (p=0.021, Mann-Whitney U-test). LogsCD163 increased significantly with increasing
      CAD extent (p=0.0036) and was significantly greater in patients with 3 vessel
      disease than in CAD- patients (p<0.001). Whereas logsCD163 correlated with CAD
      extent (Spearman r=0.22, p=0.008), logCRP did not, and sCD163 was only weakly
      correlated with CRP (r=0.19, p=0.039). Importantly, multivariate linear
      regression identified that sCD163 (p=0.0021) was a significant predictor of CAD
      extent and was independent of conventional risk factors age (p<0.0001),
      hypercholesterolemia (p=0.0023), hypertension (p=0.068), and current smoking
      (p=0.066). CONCLUSIONS: The monocyte-specific marker sCD163 is a novel potential
      plasma marker of coronary atherosclerotic burden.

PMID- 15979080
TI  - Endothelial function in conduit and resistance arteries in men with coronary
      disease.
AB  - The aims of this study were to determine whether non-invasive measurement of
      endothelial function in conduit arteries reflects that of subcutaneous resistance
      arteries measured in vitro and to examine whether there is an endothelial
      dysfunction also in resistance arteries in patients with a previous myocardial
      infarction. The brachial artery diameter responses to a hyperemic flow stimulus
      and an in vitro method, pressure myography, to directly evaluate flow-mediated
      responses in arteries obtained from biopsies of subcutaneous fat were measured in
      25 patients with a previous myocardial infarction and in 8 aged matched healthy
      subjects. Flow-mediated dilatation of the brachial artery was more pronounced in
      the healthy group compared with the group with coronary disease, 5.1 +/- 2.5% and
      2.6 +/- 2.1%, respectively (p < 0.05). The flow-mediated dilatation in
      subcutaneous arteries from CHD patients was significantly reduced compared to
      control subjects (e.g. percent change from initial preconstriction at maximum
      flow rate of 204 microl/min: 42 +/- 7% CHD (n = 25) versus 84 +/- 24% control (n
      = 8), ANOVA, p = 0.03). There was a significant correlation between flow-mediated
      dilatation of the brachial artery and maximum flow-mediated dilatation at
      microvascular level, (p < 0.01). In conclusion this study demonstrates
      endothelial dysfunction in both conduit and resistance circulation in patients
      after myocardial infarction compared to an aged-matched healthy control group.
      Furthermore, a significant and independent relationship between endothelial
      function by means of flow-mediated dilatation in large conduit arteries and
      resistance arteries was observed.

PMID- 15979081
TI  - Low serum bilirubin levels are independently and inversely related to impaired
      flow-mediated vasodilation and increased carotid intima-media thickness in both
      men and women.
AB  - BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol and its
      oxidative modification have been described to be involved in the process of
      atherogenesis. Bilirubin, an antioxidant, prevents oxidative modification of LDL
      and therefore may protect from atherosclerosis and coronary heart disease (CHD).
      Impaired brachial artery flow-mediated dilatation (FMD), which means endothelial
      dysfunction (ED) and carotid intima-media thickness (IMT) are predictors for the
      development and progression of atherosclerosis. In the present study, FMD and IMT
      were studied in healthy subjects with lower and higher serum bilirubin
      concentrations in physiological ranges. METHODS: Ninety-one healthy subjects
      between 25 and 45 years of age (47 with lower and 44 with higher serum bilirubin
      concentrations) were included in this study. Carotid IMT and brachial artery flow
      mediated dilatation was measured by means of high-resolution vascular ultrasound.
      FMD was assessed by establishing reactive hyperemia and endothelium-independent
      dilatation (EID) was determined by using sublingual isosorbide dinitrate.
      RESULTS: EDD in subjects with lower serum bilirubin concentrations was
      significantly worse than in those with higher serum bilirubin concentrations
      (11.6+/-4.4% versus 7.2+/-4.7%, respectively, p<0.0001). EID measurements were
      not significantly different between the groups (16+/-5.1% versus 16.8+/-7%,
      respectively). In addition, carotid IMT was significantly greater in subjects
      with lower serum bilirubin concentrations (0.5+/-0.13 mm versus 0.42+/-0.07 mm,
      p<0.0001). Furthermore, FMD in women with lower serum bilirubin concentrations
      was significantly lower than in women with higher serum bilirubin concentrations
      (11.5+/-4.9% and 17.5+/-4.7%, respectively, p<0.001). Accordingly, men with lower
      serum bilirubin concentrations had significantly lower FMD as compared to
      hyperbilirubinemic ones (11.7+/-3.6% versus 16.7+/-4.8%, respectively, p=0.009).
      Conversely, carotid IMT was significantly greater in both women and men with
      lower serum bilirubin concentrations compared to the subjects with elevated serum
      bilirubin concentrations (0.51+/-0.08 versus 0.41+/-0.08, p<0.001; 0.55+/-0.12
      versus 0.40+/-0.07, p=0.002, in women and men, respectively). CONCLUSION: The
      healthy subjects with lower serum bilirubin concentrations show significant ED
      and increased carotid IMT, which are predictors for atherosclerosis.

PMID- 15979082
TI  - The difference in trochlear orientation between the natural knee and current
      prosthetic knee designs; towards a truly physiological prosthetic groove
      orientation.
AB  - The patella groove of total knee replacements has evolved from a groove with a
      neutral orientation to a groove with a lateral (also referred to as valgus)
      orientation. In this study the authors questioned whether femoral components with
      a lateral groove orientation more closely approximate the configuration in the
      natural knee. The groove orientations of an implanted CKS femoral component,
      available in different sizes and with different groove orientations, were
      determined and compared with formerly published measurements of the natural
      trochlear orientation. It was found that the prosthetic groove orientations
      differed considerably from human anatomy, up to a maximum deviation of 6.4
      degrees. The orientations of the prosthetic grooves were all equal within the
      area of the natural trochlea. The area of the natural trochlea guides the patella
      between about 30 degrees and 120 degrees of knee flexion. The orientations of the
      prosthetic grooves were different in the area of the supracondylar pouch/proximal
      anterior flange. This area guides the patella between about 0 degrees and 30
      degrees of knee flexion. As this study showed a considerable deviation between
      natural and prosthetic groove orientation, an optimal prosthetic groove
      orientation, matching the average orientation in the natural knee, was
      mathematically determined.

PMID- 15979083
TI  - Hydrolyzable nonionic surfactants: stability and physicochemical properties of
      surfactants containing carbonate, ester, and amide bonds.
AB  - A linear and a branched nonionic cleavable surfactants containing a carbonate
      bond have been prepared from tetra(ethylene glycol) and an alkylchloroformate.
      The stability of these carbonate surfactants was determined by investigating
      their hydrolysis and biodegradability characteristics. The hydrolysis was
      catalyzed by alkali or enzymes (esterase from porcine liver and lipases from
      Mucor miehei and Candida antarctica B) and was monitored using 1H NMR. It was
      found that the stability toward alkali was higher for a carbonate surfactant than
      for a corresponding surfactant with an ester as weak bond. Biodegradation tests
      resulted in more than 60% degradation after 28 days for both carbonate
      surfactants. Physicochemical properties, such as critical micelle concentration
      (CMC), cloud point, area per molecule, and surface tension at the CMC, were
      determined and compared to those obtained from similar surfactants containing
      ester, amide, or ether bonds. It was found that the carbonate linkage is
      hydrophobic and that the oxycarbonyl part of the carbonate group is equivalent,
      in a formal sense, to an extra methylene group in the alkyl chain of the
      surfactant.

PMID- 15979084
TI  - On the Lagrangian/Eulerian modeling of dispersed droplet inertia: internal
      circulation transition.
AB  - This article addresses a limitation of Lagrangian methods for droplet tracking,
      when approaching the transition point of internal circulation within droplets.
      Laminar multiphase flow with dispersed droplets in a co-flowing airstream is
      considered. Analytical and numerical formulations of droplet motion are developed
      based on a Lagrangian finite difference method of droplet tracking. Cases of both
      high and low relative Reynolds numbers are formulated. The role of interfacial
      drag in cross-phase momentum exchange increases at higher relative Reynolds
      numbers. A new transition criterion is developed to characterize conditions
      leading to shear-driven non-uniformities of velocity within a droplet. This
      criterion entails a momentum Biot number, in analogy with the Biot number
      criterion for conjugate heat transfer problems involving conduction and
      convection. At sufficiently high momentum Biot numbers, appreciable changes of
      velocity within a droplet imply that Lagrangian methods become unsuitable and
      transition to Eulerian volume averaging is needed. Predicted results of
      Lagrangian modeling of droplet motion in a co-flowing airstream are presented and
      discussed.

PMID- 15979085
TI  - The effect of structural variation of alcohols on water solubilization in
      nonionic microemulsions 1. From linear to branched amphiphiles--general
      considerations.
AB  - This article is the first part of a two-part study that exemplifies how to treat
      the solubilization of water in multicomponent surfactant-based systems. In
      particular, it aims at clarifying the role of cosurfactants in water
      solubilization in these systems. The judicious selection of the components in
      such systems to maximize water solubilization is occasionally thought to be
      dictated by the chain length compatibility principle, which may be expressed
      quantitatively by the BSO (Bansal, Shah, O'Connell) equation. Here we demonstrate
      some limitations of the equation. For example, in our best model system,
      C12(EO)8/dodecane+pentanol=1:1 (by weight)/water at 27+/-0.2 degrees C, the BSO
      equation predicts that no alcohol is needed for maximum water solubilization,
      contrary to our experimental findings. We discuss how to optimize the alcohol/oil
      weight ratio needed for stabilizing four-component microemulsions. In our model
      systems C12(EO)8 or C(18:1)(EO)10/pentanol/dodecane/water, this optimal weight
      ratio is 1:1. We also highlight the difference between the effect of normal
      alcohols on water solubilization-which passes via a maximum-and their effect on
      percolation processes and structured changes of proteins, which depends solely
      upon the alcohol hydrophobicity. For the investigation of the effect of branching
      on phase behavior the utilization of an extended form of the geometrical
      branching factor F(b) is suggested. The meaning of this factor is elucidated by
      comparing it with topological indices.

PMID- 15979086
TI  - The peptide PIN changes the timing of transitory burst activation of timer-ATPase
      TIME in accordance with diapause development in eggs of the silkworm, Bombyx
      mori.
AB  - TIME is an ATPase that measures a time interval by exhibiting transitory burst
      activation in eggs of the silkworm, Bombyx mori L. PIN is a peptide that
      regulates the time measurement of TIME. To address the mode of action of PIN,
      interactions between TIME and PIN were investigated. First, TIME was mixed with
      PIN for various periods (days) at 25 degrees C. The longer TIME was mixed with
      PIN, the later the transitory burst activation of TIME ATPase activity occurred,
      while no such delay occurred at 5 degrees C. Second, the capacity of PIN to bind
      with TIME was measured at the two temperatures by fluorescence polarization. The
      binding interaction was much tighter (nearly 1000 times) at 25 degrees C than
      that at 4 degrees C. Because the log EC50 (in nM) at 4 degrees C was about 7, PIN
      must dissociate from TIME at low temperatures at the physiological concentration
      of TIME in eggs. Thus, TIME appears to be restructured into a time-measuring
      conformation by PIN at the high temperatures of summer, whereas the TIME-PIN
      complex would dissociate at the low temperatures of winter. This dissociation
      acts as the preliminary cue for the ATPase activity burst of TIME, which in turn
      causes the completion of diapause development and initiates new developmental
      programs.

PMID- 15979087
TI  - Geographic and developmental variation in expression of the circadian rhythm
      gene, timeless, in the pitcher-plant mosquito, Wyeomyia smithii.
AB  - Expression of the circadian rhythm gene timeless was investigated in the pitcher
      plant mosquito, Wyeomyia smithii (Coq.), and was found to vary with time of day,
      instar of diapause, and latitude of origin. The temporal pattern of timeless
      expression differed between the two diapausing instars and was significantly
      higher in southern (38-40 degrees N) than in northern (50 degrees N) populations,
      when diapausing instar was held constant. Expression of timeless is therefore
      both developmentally and evolutionarily variable. This result provides the first
      example of a latitudinal difference in the expression of timeless, suggesting
      that, along with evidence from other insects, timeless has the potential to
      affect photoperiodic response and its adaptive evolution in temperate seasonal
      environments.

PMID- 15979088
TI  - The HS2 enhancer of the beta-globin locus control region initiates synthesis of
      non-coding, polyadenylated RNAs independent of a cis-linked globin promoter.
AB  - The HS2 enhancer in the beta-globin locus control region (LCR) regulates
      transcription of the globin genes 10-50 kb away. Earlier studies show that a
      transcription mechanism initiated by the HS2 enhancer through the intervening DNA
      in the direction of the cis-linked promoter and gene mediates long-range enhancer
      function. Here, we further analyzed the enhancer-initiated RNAs and their mode of
      transcription from the HS2 enhancer in the endogenous genome of erythroid K562
      cells, in plasmids integrated into K562 cells and in purified DNA used as
      template in in vitro transcription reactions. We found that the HS2 enhancer was
      able to initiate transcription autonomously in the absence of a cis-linked globin
      promoter. The enhancer-initiated, intergenic RNAs were different from the mRNA
      synthesized at the promoter in several aspects. The enhancer RNAs were
      synthesized not from a defined site but from multiple sites both within and as
      far as 1 kb downstream of the enhancer. The enhancer RNAs did not appear to
      contain a normal cap structure at the 5' ends. They were polyadenylated at
      multiple sites within 3 kb downstream of their initiation sites and were
      therefore shorter than 3 kb in lengths. The enhancer RNAs remained in discrete
      spots within the nucleus and were not processed into mRNA or translated into
      proteins. These particular features of enhancer-initiated transcription indicate
      that the transcriptional complex assembled by the enhancer was different from the
      basal transcription complex assembled at the promoter. The results suggest that
      in synthesizing non-coding, intergenic RNAs, the enhancer-assembled transcription
      complex could track through the intervening DNA to reach the basal promoter
      complex and activate efficient mRNA synthesis from the promoter.

PMID- 15979089
TI  - Properties of the interaction of Arf-like protein 2 with PDEdelta.
AB  - Arf-like proteins (Arl) share certain characteristic features with the Arf
      subfamily of Ras superfamily proteins, but their function is unknown. Here, we
      show by a variety of spectroscopic techniques that Arl2, unlike most other Ras
      related proteins, has micromolar rather than picomolar affinity for nucleotides.
      As a consequence of low affinity, nucleotide dissociation rates are rather fast,
      arguing that it is not regulated by guanine nucleotide exchange factors. Arl2 is
      isolated as prey in a yeast double hybrid screen using phosphodiesterase 6delta
      (PDEdelta) as bait. This interaction is dependent on GTP, and the binding of
      PDEdelta substantially stabilizes GTP binding, increasing affinity and decreasing
      dissociation rates by a similar factor. Among all Arl proteins tested, PDEdelta
      only interacted with the closely related proteins Arl2 and Arl3, strongly
      suggesting that Arl2/3 are specific regulators of PDEdelta.

PMID- 15979090
TI  - Crystal structure of Bacillus sp. GL1 xanthan lyase complexed with a substrate:
      insights into the enzyme reaction mechanism.
AB  - Bacillus sp. GL1 xanthan lyase, a member of polysaccharide lyase family 8 (PL-8),
      acts exolytically on the side-chains of pentasaccharide-repeating polysaccharide
      xanthan and cleaves the glycosidic bond between glucuronic acid (GlcUA) and
      pyruvylated mannose (PyrMan) through a beta-elimination reaction. To clarify the
      enzyme reaction mechanism, i.e. its substrate recognition and catalytic reaction,
      we determined crystal structures of a mutant enzyme, N194A, in complexes with the
      product (PyrMan) and a substrate (pentasacharide) and in a ligand-free form at
      1.8, 2.1, and 2.3A resolution. Based on the structures of the mutant in complexes
      with the product and substrate, we found that xanthan lyase recognized the PyrMan
      residue at subsite -1 and the GlcUA residue at +1 on the xanthan side-chain and
      underwent little interaction with the main chain of the polysaccharide. The
      structure of the mutant-substrate complex also showed that the hydroxyl group of
      Tyr255 was close to both the C-5 atom of the GlcUA residue and the oxygen atom of
      the glycosidic bond to be cleaved, suggesting that Tyr255 likely acts as a
      general base that extracts the proton from C-5 of the GlcUA residue and as a
      general acid that donates the proton to the glycosidic bond. A structural
      comparison of catalytic centers of PL-8 lyases indicated that the catalytic
      reaction mechanism is shared by all members of the family PL-8, while the
      substrate recognition mechanism differs.

PMID- 15979091
TI  - Crystal structure of a heat-inducible transcriptional repressor HrcA from
      Thermotoga maritima: structural insight into DNA binding and dimerization.
AB  - All cells have a defense mechanism against a sudden heat-shock stress. Commonly,
      they express a set of proteins that protect cellular proteins from being
      denatured by heat. Among them, GroE and DnaK chaperones are representative
      defending systems, and their transcription is regulated by a heat-shock repressor
      protein HrcA. HrcA repressor controls the transcription of groE and dnaK operons
      by binding the palindromic CIRCE element, presumably as a dimer, and the activity
      of HrcA repressor is modulated by GroE chaperones. Here, we report the first
      crystal structure of a heat-inducible transcriptional repressor, HrcA, from
      Thermotoga maritima at 2.2A resolution. The Tm_HrcA protein crystallizes as a
      dimer. The monomer is composed of three domains: an N-terminal winged helix-turn
      helix domain (WH), a GAF-like domain, and an inserted dimerizing domain (IDD).
      The IDD shows a unique structural fold with an anti-parallel beta-sheet composed
      of three beta-strands sided by four alpha-helices. The Tm_HrcA dimer structure is
      formed through hydrophobic contact between the IDDs and a limited contact that
      involves conserved residues between the GAF-like domains. In the overall dimer
      structure, the two WH domains are exposed, but the conformation of these two
      domains seems to be incompatible with DNA binding. We suggest that our structure
      may represent an inactive form of the HrcA repressor. Structural implication on
      how the inactive form of HrcA may be converted to the active form by GroEL
      binding to a conserved C-terminal sequence region of HrcA is discussed.

PMID- 15979092
TI  - Construction of a cyclic nucleotide-gated KcsA K+ channel.
AB  - The ability of an ion channel to open in response to a defined stimulus is
      central to its function. In ligand-gated channels, pore opening is conferred
      through transduction of a conformational change in a gating domain to the helices
      of the pore. Here, we present the construction of a designed cyclic nucleotide
      gated (CNG) channel, named KcsA-CNG, by addition of a prokaryotic cyclic
      nucleotide-binding domain to a KcsA-derived K+ channel. This channel is
      functional in lipid bilayers at physiological pH and has the combined properties
      of both of its parent-derived components. It conducts K+ and is blocked by the K+
      channel inhibitors Na+ and agitoxin-2. Channel open times are increased by about
      two orders of magnitude compared to wild-type KcsA. The average number of open
      channels increases by approximately 50% upon addition of cAMP. Although the
      absolute open probabilities are somewhat variable from one channel to the next,
      the property of cyclic nucleotide sensitivity is very reproducible. An apparent
      Kd value of approximately 90 nM was estimated. The successful construction of a
      cyclic nucleotide-gated KcsA K+ channel suggests that it should be possible to
      produce channels that will respond to novel ligands.

PMID- 15979093
TI  - Structure of the mediator subunit cyclin C and its implications for CDK8
      function.
AB  - Cyclin C binds the cyclin-dependent kinases CDK8 and CDK3, which regulate mRNA
      transcription and the cell cycle, respectively. The crystal structure of cyclin C
      reveals two canonical five-helix repeats and a specific N-terminal helix. In
      contrast to other cyclins, the N-terminal helix is short, mobile, and in an
      exposed position that allows for interactions with proteins other than the CDKs.
      A model of the CDK8/cyclin C pair reveals two regions in the interface with
      apparently distinct roles. A conserved region explains promiscuous binding of
      cyclin C to CDK8 and CDK3, and a non-conserved region may be responsible for
      discrimination of CDK8 against other CDKs involved in transcription. A conserved
      and cyclin C-specific surface groove may recruit substrates near the CDK8 active
      site. Activation of CDKs generally involves phosphorylation of a loop at a
      threonine residue. In CDK8, this loop is longer and the threonine is absent,
      suggesting an alternative mechanism of activation that we discuss based on a CDK8
      cyclin C model.

PMID- 15979094
TI  - A sharp minimum on the mean number of steps taken in adaptive walks.
AB  - It was recently conjectured by H.A. Orr that from a random initial point on a
      random fitness landscape of alphabetic sequences with one-mutation adjacency,
      chosen from a larger class of landscapes, no adaptive algorithm can arrive at a
      local optimum in fewer than on average e-1 steps. Here, using an example in which
      the mean number of steps to a local optimum equals (A-1)/A, where A is the number
      of distinct "letters" in the "alphabet" from which sequences are constructed, it
      is shown that as originally stated, the conjecture does not hold. It is also
      demonstrated that (A-1)/A is a sharp minimum on the mean number of steps taken in
      adaptive walks on fitness landscapes of alphabetic sequences with one-mutation
      adjacency. As the example that achieves the new lower bound has properties that
      are not often considered as potential attributes for fitness landscapes-non
      identically distributed fitnesses and negative fitness correlations for adjacent
      points-a weaker set of conditions characteristic of more commonly studied fitness
      landscapes is proposed under which the lower bound on the mean length of adaptive
      walks is conjectured to equal e-1.

PMID- 15979095
TI  - Effects of dietary mulberry, Korean red ginseng, and banaba on glucose
      homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions.
AB  - Despite lack of scientific evidences to support its therapeutic efficacy, the use
      of herbal supplements has significantly increased. The purpose of this study was
      to evaluate the effects of traditional anti-diabetic herbs on the progress of
      diabetes in db/db mice, a typical non-insulin-dependent model. Five different
      experimental diets were as follows: control diet, 0.5% mulberry leaf water
      extract diet, 0.5% Korean red ginseng diet, 0.5% banaba leaf water extract diet,
      and 0.5% combination diet (mulberry leaf water extract/Korean red ginseng/banaba
      leaf water extract, 1:1:1). Blood levels of glucose, insulin, HbA1c, and
      triglyceride were measured every 2 weeks. At 12 weeks of age, animals were
      sacrificed, and tissue mRNA levels of PPAR-alpha, PPAR-gamma, and LPL were
      determined. Results indicated that mulberry leaf water extract, Korean red
      ginseng, banaba leaf water extract, and the combination of above herbs
      effectively reduced blood glucose, insulin, TG, and percent HbA1c in study
      animals (p<0.05). We also observed that the increased expressions of liver PPAR
      alpha mRNA and adipose tissue PPAR-gamma mRNA in animals fed diets supplemented
      with test herbs. The expression of liver LPL mRNA was also increased with
      experimental diets containing herbs. The efficacy was highest in animals fed the
      combination diet for all of the markers used. These results suggest that mulberry
      leaf water extract, Korean red ginseng, banaba leaf water extract, and the
      combination of these herbs fed at the level of 0.5% of the diet significantly
      increase insulin sensitivity, and improve hyperglycemia possibly through
      regulating PPAR-mediated lipid metabolism.

PMID- 15979096
TI  - Anandamide transport: a critical review.
AB  - Anandamide (AEA) uptake has been described over the last decade to occur by
      facilitated diffusion, but a protein has yet to be isolated. In some cell types,
      it has recently been suggested that AEA, an uncharged hydrophobic molecule,
      passively diffuses through the plasma membrane in a process that is not protein
      mediated. Since that observation, recent kinetics studies (using varying assay
      conditions) have both supported and denied the presence of an AEA transporter. In
      this review, we analyze the current literature exploring the mechanism of AEA
      uptake and endeavor to explain the reasons for the divergent views. One of the
      main variables among laboratories is the incubation time of the cells with AEA.
      Initial kinetics (at time points <1 min depending upon the cell type) isolate
      events that occur at the plasma membrane and are most useful to study
      saturability of uptake and effects of purported transport inhibitors upon uptake.
      Results with longer incubation times reflect events not only at the plasma
      membrane but also interactions at intracellular sites that may include enzyme(s),
      other proteins, or specialized lipid-binding domains. Furthermore, at long
      incubation times, antagonists to AEA receptors reduce AEA uptake. Another
      complicating factor in AEA transport studies is the nonspecific binding to
      plastic culture dishes. The magnitude of this effect may exceed AEA uptake into
      cells. Likewise, AEA may be released from plastic culture dishes (without cells)
      in such a manner as to mimic efflux from cells. AEA transport protocols using
      BSA, similar to the method used for fatty acid uptake studies, are gaining
      acceptance. This may improve AEA solution stability and minimize binding to
      plastic, although some groups report that BSA interferes with uptake. In response
      to criticisms that many transport inhibitors also inhibit the fatty acid amide
      hydrolase (FAAH), new compounds have recently been synthesized. Following their
      characterization in FAAH+/+ and FAAH-/- cells and transgenic mice, several
      inhibitors have been shown to have physiological activity in FAAH-/- mice. Their
      targets are now being characterized with the possibility that a protein
      transporter for AEA may be characterized.

PMID- 15979097
TI  - Antinociceptive effect of leaf essential oil from Croton sonderianus in mice.
AB  - The leaf essential oil from Croton sonderianus (EOCS) was evaluated for
      antinociceptive activity in mice using chemical and thermal models of
      nociception. Given orally, the essential oil at doses of 50, 100 and 200 mg/kg
      produced significant inhibitions on chemical nociception induced by
      intraperitoneal acetic acid and subplantar formalin or capsaicin injections.
      However, it evidenced no efficacy against thermal nociception in hot-plate test.
      More prominent inhibition of acetic acid-induced writhing and capsaicin-induced
      hind-paw licking responses was observed at 100 and 200 mg/kg of EOCS. At similar
      doses, the paw licking behavior in formalin test was more potently suppressed
      during the late phase (20-25 min, inflammatory) than in early phase (0-5 min,
      neurogenic). The EOCS-induced antinociception in both capsaicin and formalin
      tests was insensitive to naloxone (1 mg/kg, s.c.), but was significantly
      antagonized by glibenclamide (2 mg/kg, i.p.). In mice, the essential oil (100 and
      200 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor
      impaired the motor performance in rota-rod test, indicating that the observed
      antinociception is unlikely due to sedation or motor abnormality. These results
      suggest that EOCS produces antinociception possibly involving glibenclamide
      sensitive KATP+ channels, which merit further studies on its efficacy in more
      specific models of hyperalgesia and neuropathic pain.

PMID- 15979098
TI  - Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds.
AB  - A bioassay guided phytochemical study of the ethyl acetate extract of the seeds
      of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta, 23
      tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known
      triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid (2),
      2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha, 3beta,
      23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta, trihydroxyolean
      12-en-28-oic acid (5), and 2alpha, 3beta, 6beta, 23-tetrahydroxyolean-12-en-28
      oic acid (6). Their structures were established by extensive NMR spectral
      studies. The acetyl derivatives, compounds 7 and 8, were prepared from compounds
      1 and 2, respectively, to aid in their structure elucidation. The inhibition of
      cyclooxygenase-2 (COX-2) enzyme by compounds 1--6 at 100 microg/mL was 38.3%,
      39%, 37%, 49.6%, 25%, and 45.0%, respectively. However, compounds 1--6, at 100
      microg/mL, did not inhibit cyclooxygenase-1 (COX-1) enzyme. Compound 1 is a novel
      triterpenoid and compounds 1--6 are isolated for the first time from the seeds of
      P. kurroa.

PMID- 15979099
TI  - Evaluation of the cytotoxicity, cytostaticity and genotoxicity of argentatins A
      and B from Parthenium argentatum (Gray).
AB  - Argentatins A and B are abundant triterpenes present in Parthenium argentatum.
      Both compounds have shown cytotoxic properties on K562, MCF-7, PC-3, HCT-15 and
      U251 human cancer cell lines. Furthermore the cytotoxic, cytostatic and genotoxic
      effects of the argentatins on proliferating lymphocytes were evaluated using
      cytokinesis-block micronucleus test. Argentatin A had no cytostatic properties,
      but it was cytotoxic for proliferating lymphocytes at a concentration of 25
      microM (P < 0.005). On the other hand, argentatin B showed significant cytostatic
      effects (P < 0.001) at concentrations of 5 to 25 microM and it did not show
      cytotoxic effects at the same concentrations. Neither argentatin showed genotoxic
      effects in terms of micronucleus frequency in human lymphocytes. According to
      these results the argentatins are not able to cause injury on DNA by clastogenic
      or aneugenic mechanisms.

PMID- 15979100
TI  - Identification of MYCBP as a beta-catenin/LEF-1 target using DNA microarray
      analysis.
AB  - Abnormal activation of the beta-catenin signaling pathway can cause various types
      of cancer. Activation of Wnt pathway leads to stabilization of the beta-catenin
      protein, which results in its translocation to the nucleus and the formation of
      complexes with lymphoid enhancer factor-1 (LEF-1) and other T-cell factor (TCF)
      family of transcription factors to affect the transcription of target genes.
      However, the entrapment pattern of beta-catenin in the nucleus of normal
      epithelial cells differs from that in colon carcinoma cells. Normal epithelial
      cells may have different binding partners of beta-catenin and LEF-1 compared to
      tumor cells, which may result in differential expression of target genes. To
      investigate LEF-1-induced gene expression profiles, we used DNA microarrays to
      search the alterations of gene expression in normal epithelia versus cancer
      cells. Here, we reported 10 potential targets genes of beta-catenin/LEF-1. We
      showed that the expression of c-myc binding protein (MYCBP) in colon carcinoma
      cells was consistently upregulated by overexpressed LEF-1, which is confirmed by
      microarray data, RT-PCR and luciferase assay. We suggest that the MYCBP gene can
      be a direct target of beta-catenin/LEF-1 pathway through its LEF-1 binding
      site(s) in the MYCBP promoter, and that MYCBP up-regulation in colon carcinoma
      cell may play a co-activator role of c-MYC.

PMID- 15979102
TI  - Carnitine depletion in rat pups from mothers given mildronate: a model of
      carnitine deficiency in late fetal and neonatal life.
AB  - Mildronate (3-(2,2,2,-trimethylhydrazinium)propionate), is a butyrobetaine
      analogue that is known to inhibit gamma-butyrobetaine hydroxylase, the enzyme
      catalyzing the last step of carnitine biosynthesis. When administered to adult
      rats it determines a systemic carnitine deficiency and may therefore serve as an
      animal model for human carnitine depletion. The aim of this study was to evaluate
      the effect of mildronate administration to pregnant and lactating rats on tissue
      carnitine concentrations in 4- and 13-day-old rat pups. At 14 days of gestation
      female rats began to receive mildronate in the diet (200 mg/kg/d) and this
      continued for entire lactation period. Mildronate treatment determined a large
      reduction of carnitine levels in the milk of lactating dams. Because organ
      carnitine concentrations in neonatal rats are directly related to dietary supply,
      pups from mildronate group had significantly depleted levels of total carnitine
      in serum, heart, liver, muscle, brain and pancreas relative to controls, at 4 and
      13 days of age. Correspondingly, an increase in triglyceride levels was observed
      in liver, heart and muscle of mildronate pups. This is in agreement with a
      reduction of basal rate of oxidation of [U-(14)C]-palmitate to (14)CO(2) and
      (14)C-acid-soluble products observed in liver homogenates from carnitine
      deficient pups. All functional and biochemical modifications were compatible with
      a carnitine deficiency status. In conclusion our results describe a model of
      carnitine depletion in pups, suitable for the investigation of carnitine
      deficiency in fetal-neonatal nutrition, without any concomitant mildronate
      mediated metabolic alterations.

PMID- 15979101
TI  - Susceptibility of DNA to oxidative stressors in young and aging mice.
AB  - The changes that accompany aging may be a result of oxidative damage to DNA that
      accumulates as a result of aging and age-related illnesses. Furthermore, a higher
      susceptibility is thought to be more common among elderly than young individuals.
      In the present study, we examined the severity of DNA damage caused by carbon
      tetrachloride (CCl4) and H2O2 in cells from young (2 month old) and older (14
      month old) mice using both in vivo and in vitro exposures. CCl(4) is known to
      generate radical oxidative species (ROS) throughout its biotransformation in the
      liver. Therefore, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxdGuo) was quantified
      in liver DNA obtained from young and older mice treated with CCl4. In addition,
      DNA single-strand breaks were measured by the Comet assay in primary lung
      fibroblasts cultured from young and older mice and treated in vitro with H2O2.
      Intracellular ROS production and mitochondrial enzyme activity were determined in
      parallel. 8-oxodGuo levels were significantly higher in older mouse liver DNA
      than younger, and increased significantly with CCl4 treatment. When the basal DNA
      damage was subtracted, the net damage was almost equal for both. In addition,
      untreated cells cultured from older mice had significantly greater levels of
      strand breaks than cells derived from young mice. H2O2 increased the level of
      damage in both cell cultures. Our findings indicate that the DNA damage observed
      in older animals probably results from the accumulation of endogenous damage with
      age, perhaps due to insufficient repair, which enhances the injury caused by
      exposure to the toxic agents.

PMID- 15979103
TI  - Co-administration of quercetin and catechin in rats alters their absorption but
      not their metabolism.
AB  - Quercetin and catechin are among the major flavonoids in plant foods and their
      intake has been associated to a risk reduction in several degenerative diseases.
      The aim of the present study was to bring data on the bioavailability of
      quercetin and catechin when administered simultaneously. The study was performed
      on rats adapted to diets containing (i) 0.25% quercetin, or (ii) 0.25% catechin,
      or (iii) 0.25% quercetin+0.25% catechin. Quercetin, catechin and their
      metabolites were determined in plasma, urine and liver by HPLC with UV or
      coulometric detection. When quercetin and catechin were fed in association, their
      respective plasma concentration significantly decreased (-35% and -28%
      respectively), whereas the urinary and hepatic concentrations were only affected
      for quercetin (-36%). These data may be explained by a competitive interaction
      between quercetin and catechin at the digestive level, leading to a reduction of
      the intestinal absorption of quercetin and a possible delaying of catechin
      absorption over time. The simultaneous administration of quercetin and catechin
      had no effect on the formation of their glucurono and sulfo conjugates,
      indicating the absence of competition between quercetin and catechin for the
      corresponding conjugative enzymes.

PMID- 15979104
TI  - New therapies for the treatment of Parkinson's disease: adenosine A2A receptor
      antagonists.
AB  - The development of non-dopaminergic therapies for the treatment of Parkinson's
      disease (PD) has attracted much interest in recent years. Among new different
      classes of drugs, adenosine A2A receptor antagonists have emerged as best
      candidates. The present review will provide an updated summary of the results
      reported in literature concerning the effects of adenosine A2A antagonists in
      rodent and primate models of PD. These results show that A2A receptor antagonists
      improve motor deficits without inducing dyskinesia and counteract parkinsonian
      tremor. In progress clinical trials have shown that a low dose of L-DOPA plus KW
      6002 produced symptomatic relief no different from that produced by an optimal
      dose of L-DOPA alone, whereas dyskinesias were reduced rendering this class of
      compounds particularly attractive.

PMID- 15979105
TI  - Perioperative normothermia depends on intraoperative warming procedure, extent of
      the surgical intervention and age of the experimental animal.
AB  - The maintenance of a physiological body temperature during and early after
      surgical interventions in experimental animals such as rodents is often
      neglected. Therefore the positive influence of an adequate use of warming
      blankets (WB) on the rectal body temperature in rats was investigated during two
      different surgical interventions, with a special focus on possible differences
      between young adult (2.5+/-0.14 months) and adult animals (9.3+/-0.13 months).
      Anesthesia was induced with isoflurane short inhalation and maintained with
      ketamine and domitor intramuscularly. Animals were divided into ten groups
      according to (a) the age of the animals, (b) the temperature of the WB and (c)
      the kind of surgical intervention (either an intravenous [i.v.] cannulation of
      the right external jugular vein or an intra-aortal implantation of a telemetric
      transmitter or both). Results clearly show that the surface temperature of the WB
      has a major impact on the perioperative thermoregulation. The rectal body
      temperature of animals operated on a cooler WB dramatically decreased depending
      on the age of the rat and also on the extent of the surgical intervention. The
      opening of the abdominal cavity in older rats resulted in a severe hypothermia:
      they lost 5.6 degrees C compared to 3.2 degrees C in the young adult rats. The
      implantation of the i.v. catheter had no serious effect on the thermoregulation.
      In conclusion, the results clearly show that an adequate perioperative warming
      system positively influences the postoperative outcome in young adult and most
      notably in adult rats and thus enables early postoperative experiments without
      effects on measured parameters.

PMID- 15979106
TI  - Extracellular inosine modulates ERK 1/2 and p38 phosphorylation in cultured
      Sertoli cells: possible participation in TNF-alpha modulation of ERK 1/2.
AB  - Extracellular ATP and adenosine modulation of MAPKs is well described in
      different cells types, but few studies have addressed the effects of
      extracellular inosine on these kinases. Previous results showed that hydrogen
      peroxide and TNF-alpha increase extracellular inosine concentration in cultured
      Sertoli cells and this nucleoside protects Sertoli cells against hydrogen
      peroxide induced damage and participates in TNF-alpha induced nitric oxide
      production. In view of the fact that MAPKs are key mediators of the cellular
      response to a large variety of stimuli, we investigated the effect of
      extracellular inosine on the phosphorylation of ERK 1/2 and p38 MAPKs in cultured
      Sertoli cells. The involvement of this nucleoside in the activation of ERK 1/2 by
      TNF-alpha was also investigated. Inosine and the selective A1 adenosine receptor
      agonist R-PIA increases the phosphorylation of ERK 1/2 and p38, and this was
      blocked by the selective A1 adenosine receptors antagonists, CPT and DPCPX. These
      antagonists also inhibited TNF-alpha increase in the phosphorylation of ERK 1/2.
      TNF-alpha also rapidly augmented extracellular inosine concentration in cultured
      Sertoli cells. These results show that extracellular inosine modulates ERK 1/2
      and p38 in cultured Sertoli cells, possible trough A1 adenosine receptor
      activation. This nucleoside also participates in TNF-alpha modulation of ERK 1/2.

PMID- 15979107
TI  - Our resilient seas and shores.

PMID- 15979108
TI  - Evaluation of identity-by-descent probabilities for half-sibs on continuous
      genome.
AB  - A new method is provided for exact evaluation of the distribution of the amount
      of genetic material, from a chromosomal segment, shared identical-by-descent by a
      finite number of half-sibs. The interest in such distribution stems from its
      relation to the distribution of genetic material from chromosomal segments of an
      individual surviving to the next generation. The new method is superior to the
      existing one which has recently been suggested by Stefanov [V.T. Stefanov,
      Distribution of the amount of genetic material from a chromosomal segment
      surviving to the following generation. J. Appl. Probab. 41 (2004) 345]. It allows
      both faster computation and a large number of half-sibs. Relevant software codes
      are provided for automated implementation of such evaluations.

PMID- 15979109
TI  - Frontal lobe involvement in spatial span: converging studies of normal and
      impaired function.
AB  - Although monkey lesion studies involving the prefrontal cortex commonly report
      working memory deficits, and neuroimaging studies consistently show prefrontal
      involvement in such tasks, patients with damage to this region commonly fail to
      show any working memory impairment. Such a discrepancy may be due to insensitive
      testing measures for patients, as well as small, yet critical differences between
      working memory tasks in imaging and patient studies. The current study utilised a
      more sensitive measure of spatial working memory spans, based either on
      structured or unstructured spatial arrays. A PET study in normal subjects
      confirmed that both variants did indeed activate prefrontal cortex. The same
      tasks were given to frontal lobe patients and closely matched controls. Patients
      with large frontal lesions were significantly impaired on this task, with those
      patients with damage to the right dorsolateral prefrontal cortex appearing
      particularly impaired. This result demonstrates that prefrontal cortex is
      necessary for normal working memory, even in simple tasks, such as spatial span.
      It is suggested, however, that the patient deficit reflects strategic or goal
      based dysfunction, rather than storage limitations.

PMID- 15979110
TI  - The role of prolactin and testosterone in mediating seasonal differences in the
      self-grooming behavior of male meadow voles, Microtus pennsylvanicus.
AB  - Self-grooming in response to the odors of conspecifics is a form of olfactory
      communication among meadow voles. The amount of time meadow voles spend self
      grooming when they encounter the odors of conspecifics varies seasonally, with
      males targeting the odors of reproductively active females only during the
      breeding season. Other odor related behaviors in male voles such as odor
      preferences for conspecifics and the attractiveness of their odors to
      conspecifics vary seasonally as well. For male meadow voles, these behaviors are
      mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers.
      The objective of this study was to determine whether seasonal differences in the
      amount of time male meadow voles self-groom in response to odors of conspecifics
      are mediated by seasonal rhythms in their circulating T and PRL titers. We tested
      the hypothesis that high titers of both T and PRL are necessary for
      reproductively active (long-photoperiod; LP) males and sufficient for
      reproductively quiescent (short-photoperiod; SP) male voles to spend more time
      self-grooming in response to odors of LP females than to those of other
      conspecifics. Results of this study demonstrate that high titers of PRL and T are
      necessary for LP male meadow vole to self-groom more in response to odors of LP
      females as compared to those of other conspecifics, but were not sufficient to
      induce SP males to preferentially self-groom to odors of LP females. The
      endocrine control of self-grooming by LP males appears to depend upon high titers
      of both PRL and T, which matches the endocrine mediation of other odor related
      behaviors in male voles. In contrast, the endocrine tissues that underlie self
      grooming in SP male meadow voles appear to be refractory to the effects of LP
      equivalent titers of PRL and T.

PMID- 15979111
TI  - Triterpenoids from Sanguisorba officinalis.
AB  - Seven triterpenoids, i.e., 3beta-[(alpha-L-arabinopyranosyl)oxy]-19beta
      hydroxyurs-12,20(30)-dien-28-oic acid (1), 3beta-[(alpha-L-arabinopyranosyl)oxy]
      urs-11,13(18)-dien-28-oic acid beta-D-glucopyranosyl ester (2), 2alpha,3alpha,23
      trihydroxyurs-12-en-24,28-dioic acid 28-beta-D-glucopyranosyl ester (3), 3beta
      [(alpha-L-arabinopyranosyl)oxy]-urs-12,19(20)-dien-28-oic acid (4), 3beta-[(alpha
      L-arabinopyranosyl)oxy]-urs-12,19(29)-dien-28-oic acid (5), 3beta-[(alpha-L
      arabinopyranosyl)oxy]-19alpha-hydroxyolean-12-en-28-oic acid (6), 2alpha,3beta
      dihydroxy-28-norurs-12,17,19(20),21-tetraen-23-oic cid (7), together with three
      known ones (8-10), were isolated from the roots of Sanguisorba officinalis. Their
      structures were determined by spectroscopic and chemical methods. Compounds 7 and
      10 showed marginal inhibition activity against the growth of tumor cell lines.

PMID- 15979112
TI  - Public health in practice: the three domains of public health.
AB  - This paper outlines a conceptual model for public health practice by proposing
      the three domains as a framework to organize and to deliver public health
      programmes. The model builds on the recognition that public health is everybody's
      business and therefore, needs a common definitional base. Different levels of
      skill and a wide range of contributions are needed if public health programmes
      are to make the most impact. The different domains of practice help to construct
      a basis for understanding the necessary elements of the public health system and
      their interactions. Using teenage pregnancy as a case study of a public health
      programme highlights the characteristics of the model. It demonstrates not only
      the importance of the role of directors of public health in taking a population
      based overview, but also the need for multi-sectoral, multidisciplinary working.
      The relevance of the public health approach not only to primary care but also to
      the hospital-based sector becomes apparent, as does its relevance to communities,
      voluntary sector and local government. Integration of the three domains, a common
      definition and the framework for the public health system will support effective
      delivery of health improvement.

PMID- 15979113
TI  - Osteogenic differentiation within intact human embryoid bodies result in a marked
      increase in osteocalcin secretion after 12 days of in vitro culture, and
      formation of morphologically distinct nodule-like structures.
AB  - Osteogenic lineages derived from human embryonic stem cells hold much promise for
      clinical application in bone regeneration, in addition to providing a useful
      research model in developmental biology, and for pharmacological and cytotoxicity
      screening of bone-related biomaterials and drugs in vitro. Previously, osteogenic
      differentiation of human embryonic stem cells was achieved through dissociation
      of embryoid bodies by trypsinization, prior to culture with osteogenesis
      promoting medium. This study therefore attempted a new approach: that is to
      achieve osteogenesis within intact human embryoid bodies. After 22 days of
      culture in osteogenesis-promoting medium comprising a cocktail of ascorbic acid,
      beta-glycerophosphate and dexamethasone, the attached embryoid bodies exhibited
      much cellular outgrowth and migration, and formed morphologically distinct nodule
      like structures. These were somewhat similar to osteogenic nodules formed by
      mesenchymal stem cells, as reported by previous studies. Immunohistochemical
      staining and RT-PCR analysis confirmed the presence of osteogenic cells within
      these nodule-like structures. Additionally, the quantitative assay of osteocalcin
      secretion demonstrated a rapid sharp increase in osteocalcin expression on day 12
      of in vitro culture, which could suggest the appearance of differentiated
      osteoblasts from day 12 onwards. Future work will attempt to investigate whether
      other cytokines, growth factors and chemical compounds could further enhance
      osteogenesis within intact human embryoid bodies.

PMID- 15979114
TI  - Intercellular communications within the rat anterior pituitary XII:
      immunohistochemical and physiological evidences for the gap junctional coupling
      of the folliculo-stellate cells in the rat anterior pituitary.
AB  - Since Farquhar [1957. "Corticotrophs" of the rat adenohypophysis as revealed by
      electron microscopy. Anat. Rec. 127, 291] was the first to report the presence of
      agranular folliculo-stellate cells as corticotrophs in the anterior pituitary
      gland, there were no reports about electro-physiological characteristics of the
      folliculo-stellate cells because of its no hormonal activity and the chaotic
      distribution of the parenchyma cells. Male Wistar rats, aged 7 weeks with
      weighing 250--300 g, were separated into two groups. One group was used for
      immunohistochemical and light microscopical studies to detect S-100 protein and
      connexin 43. The other group was used for the electro-physiological study and
      then for the electron microscopical study to know the fine structural character
      of folliculo-stellate cells after the electro-physiological experiment. Clusters
      of S-100 protein cells (agranulated folliculo-stellate cells) and numerous
      connexin 43 positive sites on S-100 protein cells were clear in the "transitional
      zone" at which the pituitary tissue made the transition from the pars tuberalis
      to the proximal part of the anterior lobe. Penetration of electrodes to the cells
      distributed in the transitional zone showed stable membrane potential ranged
      between--27 and--67mV with no spontaneous activity. Random penetration of
      electrode showed that larger populations of cell ( approximately 80%) had
      membrane potentials with -55.6+/-5.1 mV, and less than 20% of cells had the
      resting membrane potential with -36.0+/-4.4 mV. There were two types of cell
      couplings; one major group for the recordings from cells with similar deep
      resting membrane potentials and the other for the recordings from cells with
      different resting membrane potentials. The former indicated that two cells were
      electrically coupled while the latter no electrical couples were observed.
      Carbenoxolone depolarized the membrane by 12.3+/-5.5 mV and reduced the amplitude
      of electrotonic potentials, and the response recovered by removal of
      carbenoxolone by the superfusate. The transitional zones of the pituitary glands
      examined the electrical coupling were observed by an electron microscopy. Almost
      cytological profiles were observed as intact. The results clearly indicated that
      the folliculo-stellate cell system deeply participated in the regulation of the
      anterior pituitary parallel with the portal vessel system, which was the main
      regulatory system for pituitary hormone secretion.

PMID- 15979115
TI  - Gaining a solid grip on adipogenesis.
AB  - Obesity is presently being combated by fitness regimens, drugs and diet.
      Increasing our understanding of the physiology of adipocytes, by deducing the
      regulatory pathways involved in lipid metabolism and all aspects of adipogenesis,
      will provide alternative strategies to reduce adverse problems of obesity.
      Research has suggested that mature fat cells may dedifferentiate to form
      proliferative-competent fat cell precursors. Knowledge of the dedifferentiation
      process will allow us to gain a solid grip on adipogenesis.

PMID- 15979116
TI  - Appearance of virus-like particles in Tritrichomonas foetus after drug treatment.
AB  - Tritrichomonas foetus is a parasitic protist that infects the urogenital tract of
      cattle causing bovine trichomonosis. Virus-like particles (VLPs) in protozoa have
      been reported in several parasites including Trichomonas vaginalis, a human
      flagellate, but viruses were never described in T. foetus so far. Herein we show
      for the first time the presence of VLPs in T. foetus after several drug
      treatments. They were detected by electron microscopy and were confirmed by
      immunofluorescence microscopy using antibodies anti-virus proteins. These VLPs
      were always observed in clusters of variable size. Their preferential locations
      were at the cell periphery, close to the axostyle, and interestingly in some
      cases, inside the nucleus. Their appearance occurred when the parasites were
      under drug-treatments, such as cytoskeleton-affecting drugs (colchicine,
      vinblastine, taxol, nocodazole, and griseofulvin) or drugs inducing cell death,
      such as lactacystin and H(2)O(2). We propose that cytoskeleton participates in
      trichomonads of the process of virus release or maturation. These virus particles
      were not described previously probably because they were either in low amount or
      in a latent state.

PMID- 15979117
TI  - Biomonitoring of ciguatoxin exposure in mice using blood collection cards.
AB  - Ciguatera is a human food poisoning caused by consumption of tropical and
      subtropical fish that have, through their diet, accumulated ciguatoxins in their
      tissues. This study used laboratory mice to investigate the potential to apply
      blood collection cards to biomonitor ciguatoxin exposure. Quantitation by the
      neuroblastoma cytotoxicity assay of Caribbean ciguatoxin (C-CTX-1) spiked into
      mice blood was made with good precision and recovery. The blood collected from
      mice exposed to a sublethal dose of Caribbean ciguatoxic extract (0.59 ng/g C-CTX
      1 equivalents) was analyzed and found to contain detectable toxin levels at least
      12 h post-exposure. Calculated concentration varied from 0.25 ng/ml at 30 min
      post-exposure to 0.12 ng/ml at 12 h. A dose response mice exposure revealed a
      linear dose-dependent increase of ciguatoxin activity in mice blood, with more
      polar ciguatoxin congeners contributing to 89% of the total toxicity. Finally,
      the toxin measurement in mice blood exposed to toxic extracts from the Indian
      Ocean or from the Pacific Ocean showed that the blood collection card method
      could be extended to each of the three known ciguatoxin families (C-CTX, I-CTX
      and P-CTX). The low matrix effect of extracted dried-blood samples (used at 1:10
      or 1:20 dilution) and the high sensitivity of the neuroblastoma assay (limit of
      detection 0.006 ng/ml C-CTX-1), determined that the blood collection card method
      is suitable to monitor ciguatoxin at sublethal doses in mice and opens the
      potential to be a useful procedure for fish screening, environmental risk
      assessment or clinical diagnosis of ciguatera fish poisoning in humans or marine
      mammals.

PMID- 15979118
TI  - Sludge based Bacillus thuringiensis biopesticides: viscosity impacts.
AB  - Viscosity studies were performed on raw, pre-treated (sterilised and thermal
      alkaline hydrolysed or both types of treatment) and Bacillus thuringiensis (Bt)
      fermented sludges at different solids concentration (10-40 g/L) for production of
      biopesticides. Correlations were established among rheological parameter
      (viscosity), solids (total and dissolved) concentration and entomotoxicity (Tx)
      of Bt fermented sludges. Exponential and power laws were preferentially followed
      by hydrolysed fermented compared to raw fermented sludge. Soluble chemical oxygen
      demand variation corroborated with increase in dissolved solids concentration on
      pre-treatments, contributing to changes in viscosity. Moreover, Tx was higher for
      hydrolysed fermented sludge in comparison to raw fermented sludge owing to
      increased availability of nutrients and lower viscosity that improved oxygen
      transfer. The shake flask results were reproducible in fermenter. This study will
      have major impact on selecting fermentation, harvesting and formulation
      techniques of Bt fermented sludges for biopesticide production.

PMID- 15979120
TI  - Recovery of thermophilic campylobacters from pond water and sediment and the
      problem of interference by background bacteria in enrichment culture.
AB  - The aim of this study was to address problems in the determination of
      thermophilic campylobacters in turbid pond water and sediment. Thirty sets of
      three samples of pond water (volumes 10, 100, 1000 ml) or sediment (0.1, 1.0, 5.0
      ml) were examined for the presence of thermophilic campylobacters. The different
      volumes of pond water were processed by membrane filtration followed by selective
      enrichment. The samples of sediment were subjected directly to selective
      enrichment. Presumptive isolates were confirmed by Gram stain, cell morphology,
      presence of oxidase and catalase, growth under microaerobic but not aerobic
      conditions, and PCR. Confirmed Campylobacter species were recovered only from 10
      and 100 ml samples of water and from 0.1 and 1.0 ml samples of sediments. The
      1000 ml samples of water and 5.0 ml samples of sediment never gave positive
      isolates. PCR indicated that the confirmed isolates were all either Campylobacter
      jejuni or C. coli. Enrichment cultures from 1000 ml filtrations contained the
      highest number of background bacteria. It is suggested that the processing of
      large volumes of turbid environmental water samples or of sediment is
      counterproductive and may not yield positive Campylobacter cultures. This is
      probably due to antagonistic effects of large numbers of background bacteria out
      competing campylobacters during the enrichment stage. Pilot studies to establish
      appropriate volumes of pond water or sediment samples should be undertaken before
      routine determination of campylobacters is begun.

PMID- 15979119
TI  - Mechanism of aerobic biological destabilisation of wool scour effluent emulsions.
AB  - Wool scouring effluent is a highly polluted industrial wastewater in which the
      main pollutant, wool wax, is held in a stable oil-in-water emulsion by non-ionic
      detergent. The use of microbial action to cause emulsion destabilisation has been
      proposed as a new treatment strategy for this effluent stream. This strategy aims
      at improving aerobic treatment performance by physically removing the high-COD,
      slowly bio-degradable wool wax from the system without bio-degradation. The
      mechanism by which an aerobic-mixed culture destabilises the wool scouring
      effluent emulsion was investigated. Our results show that destabilisation is due
      to partial bio-degradation of both the scouring detergent and the wool wax.
      Cleavage of the wool wax esters was the first stage in wax degradation, when 40
      50% of wax was de-emulsified. Over the same period, detergent degradation was
      low, at 7-21%. With further incubation, detergent degradation increased, aiding
      further breakdown of the emulsion. The degradation of the detergent, a
      nonylphenol ethoxylate, resulted in both a reduction in molar concentration (of
      up to 82%) and a shortening of the ethoxylate chain length. The latter reduced
      the hydrophile-lipophile balance (HLB) from 12 to approximately 7, thereby
      reducing the ability of the residual detergent to stabilise the emulsion.
      Analysis of the emulsified and de-emulsified wax fractions could not identify a
      group of compounds that were preferentially de-emulsified based on molecular
      weight or polarity. These findings will assist in using a de-emulsification
      strategy in both existing and new treatment systems in order to save on aeration
      costs and treatment times for biological treatment of this highly polluted
      wastewater.

PMID- 15979121
TI  - Treatment of oily waters using vermiculite.
AB  - The main objective of this study was to examine the removal of oil from water by
      expanded and hydrophobized vermiculite. A pH of 9 showed a higher removal
      efficiency of oil by vermiculite. Oil removal efficiencies at pH 9 were found to
      be 79%, 93%, 90%, 57% for standard mineral oil (SMO), Canola oil (CO), Kutwell
      oil (KUT45), refinery effluent (RE), respectively, in the case of expanded
      vermiculite, and 56%, 58%, 47%, 43% for SMO, CO, KUT45 and RE, respectively, for
      hydrophobized vermiculite. Kinetic data satisfied both the Lagergren and Ho
      models. Equilibrium studies showed that the Langmuir isotherm was the best-fit
      isotherm for oil removal by both expanded and hydrophobized vermiculite. The data
      showed a higher adsorptive capacity by the expanded vermiculite compared to the
      hydrophobized vermiculite. Desorption studies showed that the expanded
      vermiculite did not desorb oil to the same extent compared to hydrophobized
      vermiculite. The Freundlich isotherm was the best-fit model for desorption.
      Expanded vermiculite showed better retention than hydrophobic vermiculite. The
      results showed that the expanded vermiculite had a greater affinity for oil than
      hydrophobized vermiculite.

PMID- 15979122
TI  - Comparative study of electrochemical degradation and ozonation of nonylphenol.
AB  - Treatment of solutions of nonylphenol (NP), Triton X-100 (TrX) and phenol in a
      flow-through undivided EC reactor equipped with a Co(2+)-promoted PbO(2) anode
      and a stainless steel cathode was accompanied by consistent changes of
      absorbance, fluorescence and mass spectra of the effluents, and formation of
      aldehydes ranging from formaldehyde to decyl aldehyde. Deconvolution of the
      absorbance spectra of EC-treated NP, TrX and phenol and examination of their
      fluorescence indicated that the compounds are rapidly degraded in the reactor.
      For NP, the degradation of the target proceeded via the generation (at current
      densities <25mA/cm(2)) of benzoquinone intermediates that yielded peaks with m/z
      ratios 223, 227, 235, and 241D in the mass spectra. Their breakdown at current
      densities >10mA/cm(2) was accompanied by the release of aldehydes that were
      predominated by acetaldehyde and formaldehyde. The total yield of aldehydes
      increased with the current density, but their speciation showed little
      sensitivity to it. Deconvolution of the absorbance spectra of NP solutions
      subjected to ozonation, and analysis for reaction by-products formed in these
      conditions showed the reaction pathway in the latter case was likely to be
      similar to that observed for the EC treatment.

PMID- 15979123
TI  - Electrochemical oxidation of phenolic wastes with boron-doped diamond anodes.
AB  - The electrochemical oxidation of several phenolic aqueous wastes has been studied
      using a bench-scale plant with a single-compartment electrochemical flow cell.
      Boron-doped diamond materials were used as the anode. Complete mineralization of
      the waste was obtained in the treatment of phenols not substituted with chlorine
      or nitrogen. Chlorinated phenolic compounds were transformed into carbon dioxide;
      volatile organochlorinated compounds and nitro-substituted phenols deal with the
      formation of polymeric materials. These polymeric materials behave as final
      products or treatment intermediates depending on the nature of the initial
      pollutant. The removal of nitro- or the chloro-group from the phenolic molecule
      seems to be one of the first stages in the treatment. Non-nitrogenated or
      chlorinated carboxylic acids have been found to be the main intermediates in the
      electrochemical oxidation of all the phenolic compounds tested. The efficiencies
      of the process depend strongly on the concentration of organic pollutants and on
      their nature, and not on the current density, at least in the operation range
      studied.

PMID- 15979124
TI  - Pathways and metabolites of microbial degradation of selected acidic
      pharmaceutical and their occurrence in municipal wastewater treated by a membrane
      bioreactor.
AB  - Laboratory degradation tests with five acidic pharmaceuticals using activated
      sludge as inocculum under aerobic conditions were performed and microbial
      metabolites were analysed by liquid chromatography-mass spectrometry (LC-MS).
      Ketoprofen was partly mineralized as a sole source of carbon and energy and the
      metabolites determined by LC-MS suggest microbial ketoprofen degradation to
      proceed along the pathway known for biphenyls and related compounds. Bezafibrate,
      naproxen and ibuprofen were degraded only cometabolically whereas no
      transformation was obtained for diclofenac. Some biodegradation intermediates in
      these batch tests could be tentatively identified by means of LC-MS. The first
      step in microbial bezafibrate degradation appears to be the hydrolytic cleavage
      of the amide bond, generating well degradable 4-chlorobenzoic acid as one of the
      hydrolysis products. As previously found for mammals, ether cleavage and
      formation of desmethylnaproxen was the initial step in microbial degradation of
      naproxen. Two isomers of hydroxy-ibuprofen were detected as intermediates in the
      mineralization of ibuprofen. Laboratory studies suggest that naproxen and
      ibuprofen can be fully mineralized whereas more stable metabolites occur in
      microbial ketoprofen and bezafibrate transformation, that may deserve further
      attention. A LC-MS method for the trace analysis of these metabolites in water
      was developed and applied to municipal wastewater. Municipal wastewater treatment
      by a membrane bioreactor may gradually improve the removal of these
      pharmaceuticals.

PMID- 15979125
TI  - A study on arsenic adsorption on polymetallic sea nodule in aqueous medium.
AB  - A detailed study on As(III) and As(V) adsorption on polymetallic sea nodule in
      aqueous medium has been reported. Elemental composition of sea nodule comprises
      primarily, iron, manganese and silicon with trace quantities of aluminium,
      copper, cobalt and nickel. As(V) adsorption on sea nodule is dependent on pH
      while As(III) is insensitive to it. Adsorption data broadly follow Langmuir
      isotherm. Kinetic data follow a pseudo-second-order model for both As(III) and
      As(V). Arsenic loading on sea nodule is dependent on initial arsenic
      concentration. Optimum As(III) loading is 0.74 mg/g at 0.34 mg/L and for As(V) it
      is 0.74 mg/g at 0.78mg/L. As(III) adsorption is broadly independent of ionic
      environment. Except for PO(4)(3-), As(III) adsorption is not influenced by anions
      but cations influence it significantly. As(V) adsorption, on the other hand, is
      influenced by anions and not by cations. Experimental evidence indicates an inner
      sphere complex for As(III) and partial inner and partial outer sphere complex for
      As(V). Both As(III) and As(V) adsorptions are marked with very little desorption
      in the pH range of 2-10. Sea nodule can speciate As(III) and As(V) in groundwater
      at or above pH 6. Sea nodule was successfully tested as an adsorbent for the
      removal of arsenic from six contaminated groundwater samples of West Bengal,
      India, containing arsenic in the range 0.04-0.18mg/L.

PMID- 15979126
TI  - The Watcombe housing study: the short-term effect of improving housing conditions
      on the indoor environment.
AB  - A three-year study (1999-2001) was initiated in the UK to assess the effect of
      improving housing conditions in 3-4 bedroom, single-family unit, social rented
      sector houses on the health of the occupants. The houses were randomised into two
      groups. Phase I houses received extensive upgrading including wet central
      heating, on demand ventilation, double-glazed doors, cavity wall and roof/loft
      insulation. An identical intervention for Phase II houses was delayed for one
      year. As part of this randomised waiting list study, discrete measurements were
      made of indoor environmental variables in each house, to assess the short-term
      effects of improving housing conditions on the indoor environment. Variables
      representative of indoor environmental conditions were measured in the living
      room, bedroom and outdoors in each of the three years of the study. In 2000,
      there was a significant difference between the changes from 1999 to 2000 between
      Phase I (upgraded) and II (not then upgraded) houses for bedroom temperatures
      (p=0.002). Changes in wall surface dampness and wall dampness in Phase I houses
      were also significantly different to the change in Phase II houses in 2000
      (p=0.001), but by 2001 the Phase I houses had reverted to the same dampness
      levels they had before upgrading. The housing upgrades increased bedroom
      temperatures in all houses. Other indoor environmental variables were not
      affected.

PMID- 15979127
TI  - Voltage-dependent calcium channels and cardiac pacemaker activity: from ionic
      currents to genes.
AB  - The spontaneous activity of pacemaker cells in the sino-atrial node controls the
      heart rhythm and rate under physiological conditions. Compared to working
      myocardial cells, pacemaker cells express a specific array of ionic channels. The
      functional importance of different ionic channels in the generation and
      regulation of cardiac automaticity is currently subject of an extensive research
      effort and has long been controversial. Among families of ionic channels, Ca(2+)
      channels have been proposed to substantially contribute to pacemaking. Indeed,
      Ca(2+) channels are robustly expressed in pacemaker cells, and influence the cell
      beating rate. Furthermore, they are regulated by the activity of the autonomic
      nervous system in both a positive and negative way. In this manuscript, we will
      first discuss how the concept of the involvement of Ca(2+) channels in cardiac
      pacemaking has been proposed and then subsequently developed by the recent advent
      in the domain of cardiac physiology of gene-targeting techniques. Secondly, we
      will indicate how the specific profile of Ca(2+) channels expression in pacemaker
      tissue can help design drugs which selectively regulate the heart rhythm in the
      absence of concomitant negative inotropism. Finally, we will indicate how the new
      possibility to assign a specific gene activity to a given ionic channel involved
      in cardiac pacemaking could implement the current postgenomic research effort in
      the construction of the cardiac Physiome.

PMID- 15979128
TI  - Endogenous channels in HEK cells and potential roles in HCN ionic current
      measurements.
AB  - A transformed line of human embryonic kidney epithelial cells (HEK 293) is
      commonly used as an expression system for exogenous ion channel genes.
      Previously, it has been shown that these cells contain mRNAs for a variety of ion
      channels. Expression of some of these genes has been confirmed at the protein
      level. Patch-clamp electrophysiology experiments confirm the presence of multiple
      ion channels and molecular data agree with pharmacological profiles of identified
      channels. In this work, we show that endogenous voltage-gated potassium channels
      in HEK cells are a significant source of outward current at positive potentials.
      We show that both non-transfected HEK cells and HEK cells transfected with
      hyperpolarization-activated cyclic-nucleotide gated (HCN) channels have a
      significant amount of voltage-gated potassium (K(V)) current when certain tail
      current voltage-clamp protocols are used to assay HCN current activation.
      Specifically, tail current protocols that use a depolarized holding potential of 
      40 mV followed by hyperpolarizing pulses (-80 to -140 mV) and then a tail pulse
      potential of +20 mV indicate K(V) channels undergo closed-state inactivation at
      the more depolarized holding potential of -40 mV, followed by recovery from
      inactivation (but no activation) at hyperpolarizing potentials and high amount of
      activation at the positive tail potential. Our results indicate that pulse
      protocols with positive tail pulses are inaccurate assays for HCN current in
      certain HEK cells. Surprisingly, HEK-293 cells were found to contain mRNA for
      HCN2 and HCN3 although we have not detected a significant and consistent
      endogenous I(f)-like current in these cells.

PMID- 15979129
TI  - Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and
      progesterone (PR), p53, ki67, and neu protein in endometrial cancer.
AB  - OBJECTIVE: We aimed at investigating by immunohistochemistry the relationship
      between cyclooxygenase-2 (COX-2) and estrogen (ER), and progesterone (PR)
      receptors in a single institution series of 90 primary untreated endometrial
      cancer patients. The simultaneous assessment of p53 protein, ki67, and neu
      protein has been carried out. METHODS: Immunohistochemistry was performed on
      paraffin-embedded sections by using rabbit polyclonal antiserum against human COX
      2, anti-ER (clone 1D5), and anti-PR (clone 1A6) monoclonal antibodies, anti ki67
      (clone MIB-1) and p53 (clone DO-7), and polyclonal antibody anti human c
      erbB2/neu. RESULTS: There was no difference in the distribution of COX-2, p53,
      and neu positive cases according to ER or PR positivity, while the percentage of
      ki67 positive endometrial tumors was significantly higher in ER negative versus
      ER positive tumors (54.5% versus 31.6%, P value = 0.044). ER and PR positive
      tumors showed a statistically significant association with clinicopathological
      parameters of better clinical outcome. There was no clear association between COX
      2 positivity and any of the clinicopathological features. The percentage of ki67,
      p53, and neu positive tumors was found to be strictly related to more aggressive
      features. Only advanced stage of disease was found to be a predictor of poor
      prognosis (P value = 0.034). None of the biological parameters examined was shown
      to be associated with patient outcome. CONCLUSIONS: We showed that COX-2
      expression is not correlated with ER, PR, p53, and neu, thus suggesting that COX
      2-mediated activities may follow independent pathways. Our findings provide the
      rationale to design trials based on the combination of antihormones with
      inhibitors of COX-2 and neu in recurrent/metastatic endometrial cancer.

PMID- 15979130
TI  - Progression of conservatively treated endometrial carcinoma after full term
      pregnancy: a case report.
AB  - INTRODUCTION: We describe a case of conservatively treated endometrial
      endometrioid (EE) adenocarcinoma which showed an aggressive clinical outcome
      after pregnancy. CASE: A 30-year-old woman with a well differentiated EE
      adenocarcinoma decided to attempt a conservative approach and underwent progestin
      treatment with subsequent negative ultrasound and hysteroscopic controls. After 3
      months, she conceived and at 36 weeks of gestation, a cesarean section was
      performed with multiple negative biopsies. Eight 8 months after delivery, an
      exploratory laparotomy documented disseminated poorly differentiated EE
      adenocarcinoma. Staging work up revealed diffuse metastatic disease. Despite
      chemotherapy, the patient experienced progression of disease with fatal acute
      respiratory syndrome due to massive neoplastic pulmonary lymphangitis.
      CONCLUSION: Conservative medical management of endometrial cancer in young women
      willing to preserve their reproductive potential, carries on potential risks.
      Careful selection of cases, informed consent, and strict follow up procedures are
      mandatory.

PMID- 15979131
TI  - Primitive neuroectodermal tumor of the cervix uteri: a case report -- changing
      concepts in therapy.
AB  - BACKGROUND: Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri
      is extremely rare. Between 1987 and 2002, there have been eight cases described
      in the English literature. The treatment policies in these eight cases differed
      considerably, partly due to the rarity of the disease and to differing time
      periods of diagnosis and treatment. CASE: At the end of 2002, a 21-year-old woman
      presented with a PNET of the cervix uteri at our institute, the Erasmus Medical
      Center. For the appropriate treatment in this case, we reviewed the literature
      and decided that the treatment should be different from the local surgical
      treatment followed by additional treatments as most of the earlier reports
      describe. CONCLUSION: In view of the current knowledge of PNET belonging to the
      family of Ewing's sarcoma, and the improvement of treatment outcome in these
      tumors due to dose-intensive neo-adjuvant chemotherapy, patients with PNET of the
      cervix should be treated in accordance to the protocol for bony Ewing's sarcoma
      with multimodality therapy by means of induction chemotherapy, surgery, and
      consolidation chemotherapy.

PMID- 15979132
TI  - Abdominal carcinomatosis in women with a history of breast cancer.
AB  - OBJECTIVES: The goals of this study were to: (1) characterize the etiology of
      abdominal carcinomatosis, (2) identify clinical features predictive of primary
      ovarian/peritoneal cancer, and (3) evaluate the survival impact of cytoreductive
      surgery among patients with advanced ovarian/peritoneal cancer and a history of
      breast cancer. METHODS: Patients with a history of prior breast cancer undergoing
      surgical exploration for abdominal carcinomatosis between 1/1/88 and 12/31/02
      were retrospectively identified from tumor registry databases. Logistic
      regression analysis was used to explore clinical characteristics predictive of
      primary ovarian/peritoneal cancer versus recurrent breast cancer. Survival
      analyses and comparisons were performed using the Kaplan-Meier and Cox
      proportional hazard models. RESULTS: Seventy-nine patients underwent surgery for
      abdominal carcinomatosis a median of 5.39 years after initial breast cancer
      diagnosis. Abdominal carcinomatosis was due to primary ovarian/primary peritoneal
      cancer in 74.7% of cases. A history of Stage I breast cancer [OR = 10.73, 95%CI =
      2.6-43.7, P < 0.001] and the lack of a prior breast cancer recurrence [OR =
      10.60, 95%CI = 2.5-45.2, P < 0.001] were independently predictive of primary
      ovarian/peritoneal cancer. Among patients with primary ovarian/peritoneal cancer,
      optimal (< or =1 cm) cytoreductive surgery was associated with a median survival
      of 44.0 months compared to 18.0 months for patients with suboptimal residual
      disease [HR = 6.81, 95%CI = 3.37-13.77, P < 0.0001]. Recurrent breast cancer was
      associated with a median survival time of 6.4 months. CONCLUSIONS: Among patients
      with prior breast cancer presenting with abdominal carcinomatosis, early-stage
      disease and the absence of a prior recurrence were predictive of primary
      ovarian/peritoneal cancer. Optimal cytoreductive surgery was associated with a
      significant survival advantage for patients with primary ovarian/peritoneal
      cancer.

PMID- 15979133
TI  - Cognitive effects of dopaminergic and glutamatergic blockade in nucleus accumbens
      in pigeons.
AB  - In earlier studies it was found that glutamatergic transmission within the
      nucleus accumbens septi is involved in the performance of a learned visual shape
      discrimination in pigeons. This study examines what effects several kinds of
      glutamate and dopamine antagonists have on the same task. Pigeons were trained
      with the relevant discrimination, bilaterally implanted with cannulas into the
      nucleus accumbens and tested after various transmission blockers had been
      administered intracerebrally. SCH-23390, a D1 dopamine antagonist, at the dose
      used, had no effect, and Spiperone, a D2-dopamine and 5HT2a-serotonine
      antagonist, significantly decreased the error repeat trials. CNQX, a non-NMDA
      glutamate receptor antagonist, and Cycloleucine, an antagonist of the glycine
      allosteric site of NMDA receptors, had no effect. CGS-19755, a selective
      competitive NMDA antagonist, significantly impaired performance by significantly
      decreasing the percent correct trials and increasing the error repeat trials.
      CPPG, a II/III metabotropic glutamate antagonist, remarkably improved
      performance. MMPG, a III/II metabotropic glutamate antagonist, at the dose used,
      did not have any significant effect. The preparation employed may be a useful
      animal model of perceptual disturbances in schizophrenia.

PMID- 15979135
TI  - Monitoring ovarian cycles and pregnancy in brown brocket deer (Mazama
      gouazoubira) by measurement of fecal progesterone metabolites.
AB  - In the present study, pregnancy and the estrous cycle were monitored in captive
      brown brocket deer (Mazama gouazoubira) by measuring fecal progestagens with a
      commercial enzyme immunoassay (EIA), along with behavioral data. Fecal samples
      were collected twice a week during pregnancy and daily during the estrous cycle
      and post-partum period. It was possible to distinguish between inter-luteal and
      luteal phases of the estrous cycle. Behavioral estrus corresponded with low
      concentrations of fecal progestagens. Samples from two consecutive cycles were
      available from five hinds, and the mean estrous cycle (n=10) was 26.9+/-1.7 d
      (mean+/-S.E.M.). However, when two extreme cycles (34 and 37 d) were deleted, the
      mean estrous cycle was 24.7+/-1.2 d. Three animals became pregnant (gestation
      ranged from 208 to 215 d). After fertile breeding, progestagen concentration in
      these hinds remained among luteal phase concentrations throughout pregnancy, with
      the exception of a few peaks. Within 4 d post-partum, two hinds reached
      interluteal phase values, while one hind maintained luteal concentrations for at
      least 1 week.

PMID- 15979134
TI  - Production of a cloned calf using zona-free serial nuclear transfer.
AB  - The efficiency of generating cloned animals following somatic cell nuclear
      transfer appears to have reached a plateau, despite ongoing research to improve
      developmental outcomes. A major limitation appears in the restricted nature of
      the adult/donor cell to de-differentiate to form a totipotent nucleus. Serial
      nuclear transfer, a modified cloning technique, has increased the developmental
      competence of amphibian, murine and porcine cloned embryos. This procedure
      involves a second nuclear transfer step; pronuclear-like cloned nuclei are
      transferred into pronuclear stage zygotic cytoplasts. The present study reports
      on the development of a serial nuclear transfer technique in the bovine, based on
      a zona-free method (hand-made cloning), resulting in the birth of a cloned calf.
      Comparisons were made between embryos produced by hand-made cloning and serial
      nuclear transfer. There were no differences between in vitro development or
      differential cell counts in the blastocysts produced. Transfer of 16 serial hand
      made cloned blastocysts resulted in the production of one healthy calf (6%),
      whereas hand-made cloning resulted in the birth of 1 calf from 23 transferred
      blastocysts (4%). One serial nuclear transfer pre-term fetus had renal and
      hepatic abnormalities (previously observed in clones from this cell line).
      Although it may not be as beneficial in the bovine as in other species, normal
      placentation (size, placentomes and umbilicus) was encouraging. Refinement of
      this technique may help to identify species-specific differences in zygotic
      competence that affect reprogramming of donor cell nuclei and that may improve
      efficiency.

PMID- 15979136
TI  - Factors affecting duration of the expulsive stage of parturition and piglet birth
      intervals in sows with uncomplicated, spontaneous farrowings.
AB  - Modern pig farming is still confronted with high perinatal piglet losses which
      are mainly contributed to factors associated with the progress of piglet
      expulsion. Therefore the aim of this study was to identify sow- and piglet
      factors affecting the duration of the expulsive stage of farrowing and piglet
      birth intervals in spontaneous farrowing sows originating from five different
      breeds. In total 211 litters were investigated. Breed affected duration of the
      expulsive stage significantly: the shortest duration was found in Large White x
      Meishan F2 crossbred litters and the longest duration in Dutch Landrace litters.
      No effect of parity on the duration of the expulsive stage was found. An increase
      in littersize (P<0.01), an increase in number of stillborn piglets per litter
      (P<0.05) and a decrease of gestation length (P<0.05, independently of littersize)
      all resulted in an increased duration of the expulsive stage of farrowing. A
      curvilinear relationship between birth interval and rank (relative position in
      the birth order) of the piglets was found. Besides that, piglet birth intervals
      increased with an increasing birth weight (P<0.001). Stillborn (P<0.01) and
      posteriorly presented (P<0.05) piglets were delivered after significantly longer
      birth intervals than liveborn and anteriorly presented piglets. The results on
      sow- and piglet factors affecting duration of the expulsive stage and piglet
      birth intervals obtained in this study contribute to an increased insight into
      (patho) physiological aspects of perinatal mortality in pigs.

PMID- 15979137
TI  - Relationships among negative and positive behaviours in adolescence.
AB  - The authors calculated binary indicators of seven positive and 23 negative
      behaviours for 22,898 8th and 15,828 11th grade students who participated in the
      Oregon Healthy Teens Survey across two school years. Relationships among these
      variables, using both the Jaccard measure of co-occurrence and the relative risk
      for each member of each variable pair, given exposure to the other, showed strong
      inter-relationships within, but not between, the sets of behaviours. The
      likelihood of negative behaviours given negative behaviours was much stronger
      than the likelihood of positive behaviours given positive behaviours. Positive
      behaviours provided little protection against the likelihood of negative
      behaviors.

PMID- 15979138
TI  - Factors affecting the free radical scavenging behavior of chitosan sulfate.
AB  - Scavenging activity of hydroxyethyl chitosan sulfate (HCS) against 2,2-diphenyl-1
      picrylhydrazyl (DPPH), hydroxyl and carbon-centered radical species were studied
      using electron spin resonance (ESR) spectroscopy. In addition, its antioxidant
      activity to retard lipid peroxidation was also evaluated in a linoleic acid model
      system. HCS could scavenge DPPH (33.78%, 2.5 mg/mL) and carbon-centered radicals
      (67.74%, 0.25 mg/mL) effectively. However, chitosan sulfate did not exhibit any
      scavenging activity against hydroxyl radicals, but increased its generation. This
      was different from the published literature and was presumed due to the loss of
      chelating ability on Fe2+. This assumption could further confirm from the results
      obtained for Fe2+-ferrozine method that upon sulfation chitooligosaccharides lost
      its chelation properties. Therefore, HCS can be identified as antioxidant that
      effectively scavenges carbon centered radicals to retard lipid peroxidation.

PMID- 15979139
TI  - Engineering of a vascularized scaffold for artificial tissue and organ
      generation.
AB  - Tissue engineering is an emerging field in regenerative medicine to overcome the
      problem of end-stage organ failure. However, complex tissues and organs need a
      vascular supply to guaranty graft survival and render bioartificial organ
      function. Here we developed methods to decellularize porcine small bowl segments
      and repopulate the remaining venous and arterial tubular structures within these
      matrices with allogeneic porcine endothelial progenitor cells. Cellular adherence
      and vitality was characterized by quantitative 2-[18F]-fluoro-2'-desoxy-glucose
      (FDG) positron emission tomography (PET) and subsequent immunohistological work
      up. The generated matrices showed insulin-dependent FDG uptake predominantly in
      the region of the former vascular structures. Stain for vitality and the specific
      endothelial markers CD31, VE-Cadherin and Flk-1 matched this functional finding.
      Providing evidence for vitality up to 3 weeks post reconstitution and typical
      endothelial differentiation, these results indicate that our generated matrix
      allows the generation of complex bioartificial tissues and organs for
      experimental and future clinical application.

PMID- 15979140
TI  - A chemically defined surface for the co-culture of melanocytes and keratinocytes.
AB  - Patients with stable vitiligo can be helped surgically using transplantation of
      autologous cultured melanocytes, but there is a need for a culture methodology
      that is free from xenobiotic agents and for a simple way of delivering cultured
      melanocytes to the patient to achieve pigmentation with good wound healing. The
      aim of this study was to develop a chemically defined surface, suitable for the
      co-culture of melanocytes and keratinocytes which could be used in the future for
      the treatment vitiligo patients to achieve both restoration of pigmentation and
      good wound healing. Two keratinocyte growth media and two melanocyte growth media
      were compared; two of these were serum free. Cells were seeded on a range of
      chemically defined substrates (produced by plasma polymerisation of acrylic acid,
      allylamine or a mixture of these monomers) either as mono- or co-cultures.
      Melanocytes and keratinocytes attached and proliferated on both acid and amine
      substrates (without significant preferences), and co-cultures of cells
      proliferated more successfully than individual cultures. One media, M2, which is
      serum free, supported expansion of melanocytes and to a lesser extent
      keratinocytes on several plasma polymer substrates. In conclusion, these data
      indicate that a combination of a chemically defined substrate with M2 media
      allows serum-free co-culture of melanocytes and keratinocytes.

PMID- 15979141
TI  - Electric block current induced detachment from surgical stainless steel and
      decreased viability of Staphylococcus epidermidis.
AB  - In vitro studies investigating the influence of electric DC current on bacterial
      detachment have demonstrated that continuous currents of only 25-125 microA
      stimulated staphylococcal strains to detach from surgical stainless steel.
      However, DC currents produce more power that has to be dissipated by the skin as
      compared to alternating currents. Also, an excess of ions on the steel can cause
      negative osteogenesis and fixation results. Therefore, it is the aim of this
      paper to examine whether detachment of Staphylococcus epidermidis from stainless
      steel surfaces in a parallel plate flow chamber can also be stimulated using
      electric block currents. Block currents of 15, 60 and 100 microA with different
      frequencies (0.1-2 Hz) and duty cycles (5-50%) were applied to induce bacterial
      detachment. Block currents of 100 microA cause detachment of about 76% of
      adhering staphylococci from stainless steel, whereas in addition the remaining
      bacteria are less viable, as determined by culturing the remaining bacteria on
      agar plates. Therewith, block current-induced detachment of adhering bacteria
      from stainless steel appears to be an equally promising method to prevent
      infection of orthopaedic fixation pins and screws than application of DC
      currents.

PMID- 15979142
TI  - Brain-behaviour relationships in latent inhibition: a computational model.
AB  - In a series of studies, we applied a neural network to study the neural bases of
      latent inhibition. We first designed a model able to handle behavioral data and
      then we investigated whether structures and neural elements in the brain were
      able to carry out the operations described by network. We demonstrated that the
      network was able to describe many of the behavioral properties of LI, and
      elucidate the effects of several manipulations of the dopaminergic system, the
      hippocampus, and the nucleus accumbens on LI, as well as some of the positive
      symptoms of schizophrenia. The results support the idea that a 'conceptual
      nervous system' can be successfully used to relate brain and behavior.

PMID- 15979143
TI  - Effects of earthworm activity on fertility and heavy metal bioavailability in
      sewage sludge.
AB  - The potential for using earthworms (Eisenia fetida) to improve fertility and
      reduce copper and cadmium availability in sewage sludge was tested by laboratory
      incubation experiments. Results comparing sewage sludge with and without
      earthworm treatment showed that earthworm activity decreased the contents of
      organic matter, total nitrogen, but increased the contents of available nitrogen
      and phosphorus and had no significant effect on the contents of total phosphorus,
      total potassium and available potassium. After incubation of the sewage sludge
      with earthworms for 60 days, the contents of Cu and Cd in the earthworms
      increased with the increase of additional Cu up to 250 mg kg(-1) and Cd up to 10
      mg kg(-1). Bioconcentration factors (BCF) were higher than 1 only for Cd when the
      addition rate was lower than 5 mg kg(-1), which indicates that the earthworms can
      only accumulate Cd when the concentration of Cd is low in sewage sludge.
      Bioavailability of Cd and Cu was evaluated by applying sewage sludge with and
      without earthworm treatment to soil and then growing cabbage plants. The results
      showed that earthworm treatment increased the biomass of cabbage and decreased
      the bioaccumulation of Cd and Cu in the cabbage plants.

PMID- 15979144
TI  - Exposure to metal mixtures and human health impacts in a contaminated area in
      Nanning, China.
AB  - Cadmium and lead have been identified as very toxic metals, which are widely
      present in the environment due to natural and anthropogenic emissions. Many
      studies have shown that the food chain is the main pathway of cadmium and lead
      transfer from the environment to humans. It is well documented that many factors
      will affect their transfer through food chains. Previous investigations on heavy
      metals were mostly concentrated on one contaminant in isolation. However, in real
      environments, exposure to mixtures of metals is ubiquitous such that cadmium
      pollution is invariably being associated with lead and zinc, etc. This study
      focuses on the contamination and health effects of the metal mixtures. For this
      purpose, a dietary survey was taken for 3 groups in Nanning in October 2002.
      Samples of soils, plants (vegetables), urine and blood of humans were measured
      for Cd, Fe, Cu, Zn, Ca and Pb, in addition, the urinary indicators of renal
      dysfunction Albumin (ALB), N-acetyl-beta-D-glucosaminidase (NAG), Beta-2
      microglobulin (beta2-MG) and Retinol-binding protein (RBP) in urine were also
      measured. Results showed that soil contamination with metal mixtures had caused
      significant renal dysfunction of the local residents living in the contaminated
      area, and the dose-response curve was somewhat altered by the mixed contamination
      of Cd and Pb as well as the intake of other minerals. The importance of mixtures
      of metal contamination and human health are also discussed in this paper.

PMID- 15979145
TI  - Special issue preface.

PMID- 15979146
TI  - Impacts of sewage irrigation on heavy metal distribution and contamination in
      Beijing, China.
AB  - A potential hazard to Beijing was revealed due to the accumulation trend of heavy
      metals in agricultural soils with sewage irrigation, which results in metal
      contamination and human exposure risk. Samples including soils and plants were
      collected to assess the impacts of sewage irrigation on the irrigated farming
      area of Beijing. Concentrations of the five elements Cd, Cr, Cu, Zn, and Pb were
      determined in samples to calculate the accumulation factor and to establish a
      basis for environmental protection and the suitability of sewage irrigation for
      particular land use in the urban-rural interaction area of Beijing. Using
      reference values provided by the Beijing Background Research Cooperative Group in
      the 1970s, the pollution load index (PLI), enrichment factor (EF), and
      contamination factor (CF) of these metals were calculated. The pollution load
      indices (sewage irrigation land 3.49) of soils indicated that metal contamination
      occurred in these sites. The metal enrichment (EF of Cd 1.8, Cr 1.7, Cu 2.3, Zn
      2.0, Pb 1.9) and the metal contamination (CF of Cd 2.6, Cr 1.5, Cu 2.0, Zn 1.7,
      Pb 1.6) showed that the accumulation trend of the five toxic metals increased
      during the sewage irrigation as compared with the lower reference values than
      other region in China and world average, and that pollution with Cd, Cu, Zn, and
      Pb was exacerbated in soils. The distributions of these metals were homogeneous
      in the irrigation area, but small-scale heterogeneous spatial distribution was
      observed. Irrigation sources were found to affect heavy metal distributions in
      soils. It was suggested that heavy metal transfer from soils to plants was a key
      pathway to human health exposure to metal contamination. However, with the
      expansion of urban areas in Beijing, soil inhalation and ingestion may become
      important pathways of human exposure to metal contamination.

PMID- 15979147
TI  - Objectives and structure of the DRAIN project: an extensive study of the delivery
      from the drainage basin of the Venice Lagoon (Italy).
AB  - The Venice Lagoon and its drainage basin form a vast system, where historical and
      recent cities, large and medium-small industrial districts and intensive
      agricultural activities coexist within a peculiar environment. The drainage basin
      constituted of an ensemble of tributary sub-basins with contrasting
      characteristics and freshwater fluxes; the hydraulic pathways are generally
      complex and not univocally established. With the main objectives to measure the
      annual freshwater discharge into the Venice Lagoon and to estimate the related
      load of pollutants, an intense field activity was carried out in the ambit of the
      DRAIN project. The 12 main tributaries of the drainage basin were monitored for
      more than 2 years (1998-2000), obtaining a relevant data set of hydrodynamic,
      physico-chemical and chemical data. Integrative investigations were also
      developed in a multidisciplinary approach, covering the existing knowledge gaps
      on the hydrology and behaviour of such a complex system. The paper describes the
      characteristics of the system, the selected approach to investigate it, and the
      main project outcomes.

PMID- 15979148
TI  - Metabolism and functions of phosphatidylserine.
AB  - Phosphatidylserine (PS) is a quantitatively minor membrane phospholipid that is
      synthesized by prokaryotic and eukaryotic cells. In this review we focus on genes
      and enzymes that are involved in PS biosynthesis in bacteria, yeast, plants and
      mammalian cells and discuss the available information on the regulation of PS
      biosynthesis in these organisms. The enzymes that synthesize PS are restricted to
      endoplasmic reticulum membranes in yeast and mammalian cells, yet PS is widely
      distributed throughout other organelle membranes. Thus, mechanisms of inter
      organelle movement of PS, particularly the transport of PS from its site of
      synthesis to the site of PS decarboxylation in mitochondria, are considered. PS
      is normally asymmetrically distributed across the membrane bilayer, thus the
      mechanisms of transbilayer translocation of PS, particularly across the plasma
      membrane, are also discussed. The exposure of PS on the outside surface of cells
      is widely believed to play a key role in the removal of apoptotic cells and in
      initiation of the blood clotting cascade. PS is also the precursor of
      phosphatidylethanolamine that is made by PS decarboxylase in bacteria, yeast and
      mammalian cells. Furthermore, PS is required as a cofactor for several important
      enzymes, such as protein kinase C and Raf-1 kinase, that are involved in
      signaling pathways.

PMID- 15979149
TI  - Stressful life events and onset of mood disorders in children of bipolar parents
      during 14-month follow-up.
AB  - BACKGROUND: Although multiple studies have examined the association between
      stressful life events (SLEs) and the development of mood disorders, the exact
      nature of the association and the degree to which it is independent from familial
      loading (FL) and gender-specific are still not fully elucidated. AIMS: To study
      the association between person-independent and -dependent SLEs and first onset or
      recurrence of a DSM-IV mood disorder episode (MDE) in offspring of bipolar
      parents. To examine interaction effects of SLEs with familial loading and gender.
      METHOD: Offspring of bipolar parents (N=132) were assessed with the K-LEDS, the
      FHRDC and the K-SADS. Logistic regression analysis was used to examine main and
      interaction effects of various operationalizations of SLEs, familial loading and
      gender. RESULTS: Dependent SLEs were more likely to occur before onset among the
      13 offspring who had a MDE onset during the 14-month follow-up (39%) than in a
      comparable period among the 67 controls without any lifetime diagnosis (10%).
      Associations were slightly stronger for first onsets than for recurrences. The
      association between SLEs and MDE onset/recurrence was independent of socio
      demographic characteristics and familial loading, but disappeared when adjusted
      for baseline anxious/depressive symptoms. Gender and familial loading did not
      modify the influence of any SLE measure on the development of mood disorders.
      CONCLUSIONS: In this sample of bipolar offspring dependent stressful SLEs
      triggered the onset of MDEs, but this association disappeared after adjustment of
      prior anxious/depressive symptoms, indicating that the association between SLEs
      and MDE is probably a spurious association. No interaction was found between SLE
      and FL and gender. Prior anxious/depressive symptoms seem to increase the risk
      for both occurrence of dependent SLEs and MDE onset or recurrence. LIMITATIONS:
      Limited statistical power due to small number of MDE onsets.

PMID- 15979150
TI  - Risk factors associated with the development of postpartum mood disorders.
AB  - BACKGROUND: Various factors have been reported to be associated with the
      development of postpartum mood disorders. The relationship between postpartum
      mood disorders and putatively hormone-related phenomena such as premenstrual
      dysphoric disorder (PMDD) is unclear. This study attempts to determine whether
      such mood phenomena are risk factors for postpartum mood disorders. METHODS:
      Postpartum women (n=1800) were assessed for risk factors for postpartum mood
      disorders during the first 2-4 days after parturition. Of these, 133 were defined
      as "high risk" and 109 as "low risk" according to fixed criteria. A structured
      phone diagnostic interview was performed at 6-8 weeks postpartum to assess for
      the presence of postpartum depression or the blues. RESULTS: Premenstrual
      dysphoric disorder (PMDD), mood symptoms during the first 2-4 days postpartum, a
      past history of depression and mood symptoms during past oral contraceptive use,
      were found to be significant risk factors for postpartum mood disorders. Women at
      high risk for postpartum mood disorders had a 9.3-, 1.5-, 1.6- and 2.6-fold
      increase in risk for major depression, minor depression, the blues and adjustment
      disorder respectively compared to women at low risk. LIMITATIONS: While the study
      design is prospective, it is limited by the retrospective assessment of risk
      factors. CONCLUSIONS: This study provides preliminary evidence that putatively
      hormone-related phenomena such as PMDD are related to the occurrence of
      postpartum mood disorders. The results go some way to support the hypothesis that
      the etiology for postpartum mood disorders may be related to differential
      hormonal sensitivity. Such risk factors should be included in any assessment of
      the risk for these disorders.

PMID- 15979151
TI  - Efficacy, predictors of therapy response, and safety of sertraline in routine
      clinical practice: prospective, open-label, non-interventional postmarketing
      surveillance study in 1878 patients.
AB  - BACKGROUND: It is well established that subjects participating in controlled
      clinical trials may not be representative of patients seen in actual practice.
      Given that efficacy and safety of sertraline have been investigated almost
      exclusively in controlled clinical trials, the aim of this study was to
      investigate efficacy, safety, and predictors of treatment response to sertraline
      in routine clinical practice. METHODS: A total of 1878 depressed outpatients
      (69.5% female; mean age, 50.3 years) participated in this prospective, open
      label, non-interventional, postmarketing surveillance study of sertraline. The
      primary study outcome was change in depression severity as assessed independently
      with the Patient Health Questionnaire (PHQ-9) depression scale and Clinical
      Global Impression (CGI) scales after 12 weeks of treatment. Stepwise logistic
      regression analyses were used to identify independent predictors of treatment
      response. RESULTS: Using standard criteria to define clinical improvement,
      responder rates were 87.7% (PHQ-9) and 87.2% (CGI), respectively. Remission, i.e.
      a PHQ-9 score of 5 or below, occurred in 56.9% of patients. Independent baseline
      predictors of CGI treatment response were: non-chronic course of depression
      (OR=2.8, p < 0.001), non-psychiatric treatment setting (OR=2.5, p < 0.001),
      absence of comorbid physical disease (OR=1.9, p < 0.001), depression-related work
      disability (OR=1.9, p < 0.001), and no previous antidepressant medication
      (OR=1.5, p=0.03). Adverse events were reported by 4.8% of patients. LIMITATIONS:
      Lack of a control group limits the conclusions that can be drawn from this study.
      CONCLUSIONS: For treatment of depressive disorders in routine outpatient
      settings, sertraline is safe and efficacious. Patients without prior episodes of
      depression, without medical comorbidity, and those with higher levels of
      depression-related functional limitations are most likely to respond to
      sertraline treatment.

PMID- 15979152
TI  - Prevalence of respiratory disorders in first-degree relatives of panic disorder
      patients.
AB  - BACKGROUND: Panic Disorder (PD) patients often report a history of respiratory
      pathology, such as asthma. It is known that both PD and respiratory disorders,
      like asthma, run in families. A common diathesis for PD and some respiratory
      disorders may be present both in PD patients and their first-degree relatives. We
      examined whether the lifetime prevalence of respiratory disorders is higher in
      first-degree relatives of PD patients than in first-degree relatives of patients
      with other anxiety disorders. METHODS: The lifetime history of respiratory
      pathology was assessed in 379 first-degree relatives of patients with an anxiety
      disorder by means of a questionnaire. RESULTS: We found the first-degree
      relatives of PD patients to report more chronic obstructive pulmonary diseases
      (COPD) in general (24.8%) and asthma (10.5%) in particular than the comparison
      group (13.2% and 3.3%, respectively). LIMITATIONS: Our data rely on retrospective
      self-reports. CONCLUSIONS: Our findings are consistent with and extend previous
      studies suggesting a specific association between COPD, asthma in particular, and
      PD.

PMID- 15979153
TI  - First incidence depression in the Lundby Study: a comparison of the two time
      periods 1947-1972 and 1972-1997.
AB  - BACKGROUND: The Lundby Study is a prospective, longitudinal study on a total
      population consisting of 3563 subjects during 50 years. This study compares first
      incidence rates of depression and cumulative probabilities for developing a
      depression over the two time periods 1947-1972 and 1972-1997. METHOD: The Lundby
      Study started in 1947. Follow-ups were carried out in 1957 and in 1972. In 1997
      the surviving subjects (N=1797) were interviewed by psychiatrists with a semi
      structured interview. Best-estimate consensus diagnoses were used and ICD-10 and
      DSM-IV diagnoses were added. Further, 1030 subjects who had died during the last
      follow-up period 1972-1997 were investigated. RESULTS: Women had higher incidence
      rates than men in both periods. The average annual incidence rate was lower for
      women and tended to be lower for men 1972-1997 as compared with 1947-1972. The
      cumulative probability for developing a depression was 22.5% for men and 30.7%
      for women 1972-1997. In 1947-1972 the corresponding figures were 22.8% in men and
      35.7% in women. LIMITATIONS: The recall period is of considerable length,
      probably introducing recall bias. The inter-rater reliability over 50 years is
      fairly acceptable concerning depression. CONCLUSION: Lower annual standardised
      incidence rates were seen in 1972-1997 compared with 1947-1972. These findings
      suggest that the trend of increasing rates of depression in the Lundby cohort has
      terminated. Incidence rates and cumulative probabilities to develop a depression
      were higher for women than for men, indicating that gender differences continue
      to play a role.

PMID- 15979154
TI  - Reduced specificity of autobiographical memory: a mediator between rumination and
      ineffective social problem-solving in major depression?
AB  - BACKGROUND: Depressed individuals display a deficit in effectively solving social
      problem situations (e.g., []). Recent research suggests that rumination may
      interfere with such effective problem-solving (e.g., []). However, little is
      known, as yet, about the mechanisms that are underlying this relation between
      rumination and poor problem-solving. The present study investigated the role of
      reduced specificity of autobiographical memories as a mediator of this
      relationship. METHODS: 24 depressed patients (15 women) completed the
      Autobiographical Memory Test (AMT), the Means-Ends Problem-Solving Task (MEPS),
      the Ruminative Response Scale (RRS) and the Rumination on Sadness Scale (RSS).
      RESULTS: Consistent with previous studies, rumination, ineffective problem
      solving and reduced memory specificity were significantly associated. Regression
      analyses further extended these findings by showing that reduced memory
      specificity mediated the association between rumination and problem-solving
      effectiveness. LIMITATIONS: The correlational nature of this study limits to some
      extent the conclusions that can be drawn on the directionality of the observed
      relationships. CONCLUSIONS: Results offer support for the idea that lack of
      autobiographical memory specificity mediates the known relationship between
      rumination and poor problem-solving.

PMID- 15979155
TI  - Cognitive, physiological, and personality correlates of recurrence of depression.
AB  - BACKGROUND: The risk of recurrence in depressive disorder is high and increases
      with the number of episodes. We investigated whether individuals with a history
      of recurrent depression deviate from individuals with a single episode, as
      regards risk-related variables in 3 different domains of depression research.
      METHODS: Participants were 102 outpatients with major depressive disorder
      remitted from an episode (60 recurrent, 42 nonrecurrent). We assessed the
      perception of emotions from vocal stimuli, 24-h urinary free cortisol, and
      neuroticism. RESULTS: The recurrent group had higher cortisol levels than the
      nonrecurrent group, and recurrent women also had a more negative perception than
      nonrecurrent women. These results were independent of each other, and could also
      not be accounted for by neuroticism or residual symptoms. Gender differences were
      found in all 3 domains. LIMITATIONS: The cross-sectional design limits the
      possibility to draw conclusions on the causality of the observed effects.
      CONCLUSIONS: Remitted outpatients with recurrent depression deviate from remitted
      outpatients with single episode depression as regards physiology and social
      cognition, in a way that may increase their risk of the development of subsequent
      episodes. The results may have implications for prophylactic treatment
      strategies.

PMID- 15979156
TI  - Characterization of cDNA and the genomic sequence encoding canine neural-cell
      adhesion molecule, CD56/N-CAM.
AB  - The neural-cell adhesion molecule, CD56/N-CAM is a member of the immunoglobulin
      superfamily expressed by various tissues and cells, including natural killer (NK)
      cells. Despite the importance of CD56 as a marker for identifying NK cells in
      circulating blood, canine CD56 has not been identified. In the present study, we
      identified the canine counterparts of the 140-kDa (CD56-140) and 120-kDa (CD56
      120) isoforms of human DC56. Both of amino acid sequences encoded by the canine
      CD56-140 and -120 cDNA showed high homology with those of human (both 96%
      homology), having well-conserved domains (five immunoglobulin, two fibronectin
      type III, and transmembrane and intracellular or glycosylphosphatidylinositol
      linked domain) among various species (human, mouse, and feline). We revealed that
      the transcripts of canine CD56-140 and -120 arise from alternative mRNA splicing
      from a single gene located on canine chromosome 5. Moreover, the mRNA encoding
      canine CD56-140 was expressed at high levels constitutively by nervous system and
      endocrine tissues as has shown in other animals.

PMID- 15979157
TI  - Immune mechanisms of pathogenetic synergy in concurrent bovine pulmonary
      infection with Haemophilus somnus and bovine respiratory syncytial virus.
AB  - Bovine respiratory syncytial virus (BRSV) and Haemophilus somnus are two bovine
      respiratory pathogens that cause disease singly or as part of a polymicrobial
      infection. BRSV infection is often associated with a predisposition towards
      production of a T helper type 2 (Th2) response and IgE production. In contrast,
      an IgG2 response to H. somnus has been shown to be most important for recovery.
      An experiment was performed to evaluate the hypothesis that infection with H.
      somnus on day 6 of experimental BRSV infection would result in disease
      enhancement and potentially an altered immune response when compared with single
      infection. Three groups of calves were either dually infected or singly infected
      with H. somnus or BRSV. Serum and bronchoalveolar lavage fluid (BALF) pathogen
      specific IgG1, IgG2, IgE, and IgA responses were evaluated by ELISA. TaqMan RT
      PCR was used to examine cytokine gene expression by PBMC and BAL cells. Clinical
      signs were evaluated for 28 days after BRSV infection, followed by necropsy and
      histological examination of the lungs. In dually infected calves, disease was
      significantly more severe, H. somnus was isolated from the lungs at necropsy, and
      high IgE and IgG responses were detected to H. somnus antigens. Cytokine profiles
      on day 27 were elevated in dually infected calves, but did not reflect a skewed
      profile. These results contrasted with singly infected calves that were
      essentially normal by day 10 of infection and lacked both lung pathology and the
      presence of H. somnus in the lung at necropsy. The increase in IgE antibodies
      specific for antigens of H. somnus presents a possible mechanism for pathogenesis
      of the disease enhancement.

PMID- 15979158
TI  - The uptake and degradation of DNA is impaired in macrophages and dendritic cells
      from NZB/W F(1) mice.
AB  - DNA/anti-DNA Ab immune complexes seem to play the critical roles in the
      development of systemic lupus erythematosus (SLE). However, little is known about
      the removal of DNA by MPhi and DC. We found that elicited peritoneal MPhis and BM
      derived DCs from a lupus-prone strain of New Zealand Black/White F(1) (NZB/W)
      mice showed impaired DNA uptake and degradation compared with those from control
      ICR mice. The impairment was mainly observed as the reduced degradation of DNA
      probably in endosomal compartment and this impaired DNA degradation might, at
      least in part, result from the reduced DNA uptake in these phagocytic cells. In
      addition, these impairments was not related to the disease progression since the
      cells from diseased, 6-month-old NZB/W mice as well as the cells from
      prediseased, 5-week-old NZB/W mice also exhibited the similar impairment. We also
      found that the MPhis and DCs of diseased NZB/W mice showed reduced DNA binding at
      4 degrees C. However, this reduced DNA binding could be restored to the control
      level by pretreatment with DNase. Interestingly, this pretreatment had little
      effect on the DNA uptake in MPhis and DCs of diseased NZB/W mice at 37 degrees C.
      Hence, the present results imply an impaired function of lupus MPhis and DCs of
      NZB/W mice to cause retained DNA clearance.

PMID- 15979159
TI  - E-selectin A561C and G98T polymorphisms influence susceptibility and course of
      multiple sclerosis.
AB  - Three hundred seven patients with MS and 300 controls were genotyped for G98T and
      A561C SNPs in the E-selectin gene, and genetic data were correlated with the
      course of the disease. The frequency of the T/T genotype of the G98T SNP was
      significantly increased in RR-MS patients compared with controls, while was
      absent in PP-MS. The frequency of the A561C SNP was significantly decreased in SP
      MS compared with benign RR-MS. The T/T genotype of the G98T SNP is likely to
      confer an increased risk to develop MS. The A561C polymorphism seems to act as
      protective factor towards the progression to SP-MS.

PMID- 15979160
TI  - Detection of herpesvirus type 8 (HHV8) in children's tonsils and adenoids by
      immunohistochemistry and in situ hybridization.
AB  - OBJECTIVE: Human herpesvirus 8 (HHV8) has been associated with multicentric
      Castleman's disease, Kaposi's sarcoma and effusion non-Hodgkin's lymphoma.
      Epidemiological studies have shown seropositivity in variable proportions of
      populations. It seems to be sexually transmitted among adults and through oral
      contact among children. The virus has been demonstrated in desquamating oral
      epithelial cells, but there is no report on its presence in the Waldeyer's ring.
      The purpose of the present study is to detect HHV8 in tonsils and adenoids from
      children up to 20 years of age in which these organs had been surgically removed
      due to hypertrophy, using immunohistochemistry and in situ hybridization.
      METHODS: Paraffin wax-embedded sections consisting of 181 tonsils and 162
      adenoids from 293 patients were analyzed. HHV8 was detected by
      immunohistochemistry (IHC) using the anti-LNA1 antibody (Novocastra) and the
      LSAB+ detection system (Dako). For the in situ hybridization (ISH), the T1-1
      probe for the viral mRNA and the detection system used were provided by
      Novocastra. RESULTS: In 20 cases (6.83%), HHV8 was detected in cells
      morphologically characterized as lymphoid. In three of them epithelial cells were
      also positive. In 19 cases, the virus was detected in tonsils and in just 1 case
      in an adenoid. In all 20 cases detection was possible by ISH, whereas in only 2
      of them there was a concomitant positivity by IHC. CONCLUSION: Our data support
      the oral route of contamination by HHV8 in children, in whom tonsils and adenoids
      may harbor the virus. It is found especially in tonsils and only rarely in
      adenoids. In these organs, ISH is the method of choice to detect this virus,
      probably due to the small amount of viral proteins.

PMID- 15979161
TI  - Day-case adenoidectomy: outcomes are improved using suction coagulation and
      prophylactic anti-emetic treatment.
AB  - In 2004, the Department of Health published 10 High Impact Changes across the
      NHS. Of these, the first was treating day surgery as the norm for elective
      operations, releasing up to half a million in-patient beds each year.
      Adenoidectomy is an operation commonly performed in children for upper
      respiratory tract obstruction and as part of the surgical management of otitis
      media with effusion. Many surgeons consider the traditional curettage
      adenoidectomy as an unsatisfactory operation because it is performed blind, and
      is associated with varying reported levels of post-operative bleeding. Concern
      about the risk of bleeding and the frequent occurrence of post-operative nausea
      and vomiting have discouraged many surgeons from adopting adenoidectomy as a day
      case procedure. We have audited the management and discharge of a cohort of 72
      children undergoing traditional curettage adenoidectomy. Based on the results, we
      have completed the audit loop, by managing a second cohort of 77 children by
      suction coagulation adenoidectomy. An anaesthetic protocol has been designed to
      reduce post-operative nausea and vomiting, and facilitate same day discharge from
      hospital. The rate of post-operative nausea and vomiting fell from 21 to 1.3%,
      and the post-operative bleeding from 9.7% to nil. Discharge on the day of
      operation rose from 40.3 to 100%. Our audit confirms that these measures permit
      safe, day-case adenoidectomy.

PMID- 15979162
TI  - Beneficial effects of Ebselen on corrosive esophageal burns of rats.
AB  - AIM: This study was evaluated to investigate the efficacy of Ebselen, which is an
      organoselenium compound and glutathione peroxidase mimic, on the prevention of
      stricture development after esophageal caustic injuries in the rat. METHODS:
      Thirty healthy male Wistar albino rats were utilized in this study. The rats were
      randomly allotted into one of three experimental groups: group A (sham) animals
      were uninjured. Caustic esophageal burn was created by applying 1 ml of 37.5%
      NaOH to the distal esophagus. Group B rats were injured but untreated. Group C
      rats were injured and received Ebselen (10 mg/kg/day) via the oral route. Blood
      and tissue samples for the biochemical and histopathological analysis were taken
      all rats at the end (28th day) of the experiment. Oxidative stress is believed to
      play a role in the pathogenesis of corrosive esophageal burns. To assess changes
      in the cellular antioxidant defense system, we measured the activities of
      antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase
      (SOD), and catalase (CAT)) in esophagus homogenates. We also measured esophageal
      tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine
      whether there is an imbalance between oxidant and antioxidant status. Efficacy of
      the treatment was assessed by measuring the stenosis index and histopathologic
      damage score and biochemically by determining tissue hydroxyproline content,
      lipid peroxidation and antioxidant enzyme levels. RESULTS: The stenosis index in
      group B was significantly increased compared with group A and C (P<0.05). The
      hydroxyproline level was significantly increased in group B compared with group A
      and C (P<0.05). In group B, the histopathologic damage score was significantly
      higher than in group C (P<0.05). Treatment with Ebselen decreased tissue
      hydroxyproline levels, histological damage, and the stenosis index. Caustic
      esophageal burn increased the lipid peroxidation and also decreased the
      antioxidant enzyme levels in group B. Ebselen treatments for 28 days decreased
      the elevated lipid peroxidation and also increased the reduced antioxidant enzyme
      levels. Live weights of the rats was significantly decreased in group B compared
      with group A and C (P<0.05). CONCLUSION: It is concluded that Ebselen has a
      preventive effect in the development of fibrosis and decrease the lipid
      peroxidation, and increase the antioxidant defense system activity in an
      experimental model of corrosive esophagitis in rats.

PMID- 15979163
TI  - Infantile congenital petrosal cholesteatoma: a case report and literature review.
AB  - Congenital cholesteatoma of the middle ear is frequently seen in younger children
      including infant. By contrast, that of the petrous bone is rarely seen in younger
      children. We report an exceptional case occurring in 23-month-old infant who
      presented with unilateral facial nerve paralysis at about 18-month-old. Computed
      tomography and magnetic resonance imaging revealed congenital cholesteatoma
      measuring approximately 2 cm in the area of the right geniculate ganglion. The
      mass was completely eradicated via the middle fossa approach, which allowed for
      preservation of hearing. The facial nerve maintained intact during surgery and
      paralysis showed partial recovery after the operation. To our knowledge, the
      present case seems to be the youngest case of congenital petrosal cholesteatoma
      reported, and also demonstrates congenital petrosal cholesteatoma could exhibit
      facial nerve paralysis in early childhood.

PMID- 15979164
TI  - Memory consolidation and reconsolidation: what is the role of sleep?
AB  - Memory consolidation and reconsolidation reflect molecular, cellular and systems
      level processes that convert labile memory representations into more permanent
      ones, available for continued reactivation and recall over extended periods of
      time. Here, we discuss the complexities of consolidation and reconsolidation, and
      suggest they should be viewed not as all-or-none phenomena, but as a continuing
      series of biological adjustments that enhance both the efficiency and the utility
      of stored memories over time and in response to changing needs of the organism.
      As such, consolidation and reconsolidation might be better thought of as memory
      organization and reorganization. A rapidly growing body of evidence suggests that
      many of these processes are optimally engaged during sleep.

PMID- 15979165
TI  - Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins.
AB  - Botulinum neurotoxins are the most potent toxins designed by nature. They are
      produced by Clostridium bacteria to cause long-lasting paralysis and death.
      However, in the past century one member of the botulinum family--botulinum
      neurotoxin type A--has been put to good use, and is now widely employed in
      clinical neurology and, even more often, in beauty clinics. This article will
      critically assess the value of individual members of the botulinum family for
      experimental neuroscience and medicine. The seven botulinum neurotoxins all act
      by targeting the same vesicle fusion machinery, and yet they cause paralysis of
      different durations. The distinct behaviors of botulinum neurotoxins will be
      discussed, with the aim of highlighting advantages and limitations for their
      future exploitation.

PMID- 15979166
TI  - For K+ channels, Na+ is the new Ca2+.
AB  - Although K+ channels activated by Ca2+ have long been known to shape neuronal
      excitability, evidence is accumulating that K+ channels sensitive to
      intracellular Na+, termed K(Na) channels, have an equally significant role. K(Na)
      channels contribute to adaptation of firing rate and to slow
      afterhyperpolarizations that follow repetitive firing. In certain neurons, they
      also appear to be activated by Na+ influx accompanying a single spike. Two genes
      encoding these channels, Slick and Slack, are expressed throughout the brain. The
      spatial localization of K(Na) channels along axons, dendrites and somata appears
      to be highly cell-type specific. Their molecular properties also suggest that
      these channels contribute to the response of neurons to hypoxia.

PMID- 15979167
TI  - The many roles of starburst amacrine cells.
AB  - Starburst amacrine cells release two classical neurotransmitters, ACh and GABA.
      In a tour de force of paired-cell recording, Zheng et al. now show that the
      starburst cells are mutually excitatory during early development but mutually
      inhibitory in adult animals. The change occurs by remodeling of both the
      cholinergic and the GABAergic synapses between starburst cells. The finding gives
      a precise mechanistic basis for the developmental waves of activity in the
      retina.

PMID- 15979168
TI  - Choosing the correct functional assay: a comprehensive assessment of functional
      tests in the rat.
AB  - While there are several ways to quantify peripheral nerve regeneration; the true
      measure of successful outcome is functional recovery. Functional tests are
      relatively easily conducted in human subjects; however it is more difficult in a
      laboratory animal. The laboratory rat is an excellent animal model of peripheral
      nerve injury and has been used extensively in the field of peripheral nerve
      research. Due to the intense interest in the rat as an experimental model,
      functional assays have been reported. In an effort to provide a resource to which
      investigators can refer when considering the most appropriate functional assay
      for a given experiment, the authors have compiled and tabulated the available
      functional tests applicable to various models of rat nerve injury.

PMID- 15979169
TI  - The kappa-opioid receptor is involved in the stimulating effect of nicotine on
      adrenocortical activity but not in nicotine induced anxiety.
AB  - The kappa (kappa) opioid system appears to interact with nicotine in the
      modulation of locomotion and addiction related processes. In this study we have
      investigated the possible implication of the kappa-opioid system in the effects
      of nicotine on anxiety and adrenocortical activity. In two different experiments,
      we analysed the possible interaction between nicotine (0.5 mg/kg i.p.) and either
      the kappa-opioid receptor antagonist nor-binaltorphimine (5 mg/kg i.p.) or the
      kappa-opioid receptor agonist U50,488H (1 mg/kg s.c.). Behavioural and endocrine
      experiments were performed in different groups of animals. Animals were exposed
      to the holeboard immediately followed by the plus-maze. Serum corticosterone
      levels were determined by radioimmunoassay. Nicotine induced an anxiogenic-like
      effect in the plus-maze and a significant decrease of holeboard activity. The
      anxiogenic-like effect in the plus-maze was not modified by any of the kappa
      opioid receptor ligands. Nicotine also induced a significant increase in the
      corticosterone levels, and the kappa antagonist, which did not exert any effect
      per se, antagonised this effect. The kappa-agonist U50,488H induced a significant
      increase in corticosterone concentration when administered alone. We provide the
      first evidence for the involvement of the kappa-opioid receptor in the
      stimulatory effect of nicotine on adrenocortical activity.

PMID- 15979170
TI  - Maize cystatins respond to developmental cues, cold stress and drought.
AB  - Comprehensive searches of maize EST data allowed us to identify 8 novel Corn
      Cystatin (CC) genes in addition to the previously known genes CCI and CCII. The
      deduced amino acid sequences of all 10 genes contain the typical cystatin family
      signature. In addition, they show an extended overall similarity with cystatins
      from other species that belong to several different phyto-cystatin subfamilies.
      To gain further insight into their respective roles in the maize plant, gene
      specific expression profiles were established by semi-quantitative RT-PCR. While
      7 CC genes were expressed in two or more tissues varying from gene to gene, CCI
      was preferentially expressed in immature tassels and CC8 and CC10 in developing
      kernels. As shown by in situ hybridisation of maize kernels, CC8 was specifically
      expressed in the basal region of the endosperm and CC10 both in the starchy
      endosperm and the scutellum of the embryo. The remaining, not kernel-specific
      genes, all had distinct expression kinetics during kernel development, generally
      with peaks during the early stages. In addition to developmental regulation, the
      effect of cold stress and water starvation were tested on cystatin expression.
      Two genes (CC8 and CC9) were induced by cold stress and 5 genes (CCII, CC3, CC4,
      CC5 and CC9) were down-regulated in response to water starvation. Taken together
      our data suggest distinct functions for CC genes in the maize plant.

PMID- 15979171
TI  - Prognostic impact of autonomic information flow in multiple organ dysfunction
      syndrome patients.
AB  - BACKGROUND: Multiple organ dysfunction syndrome (MODS) is the sequential failure
      of several organ systems after a trigger event, like cardiogenic shock or
      decompensated heart failure. Mortality is high, up to 70%. Autonomic dysfunction
      (AD) may substantially contribute to the development of MODS. In cardiology, it
      has recently been shown that nonlinear parameters could predict mortality. Our
      study aimed at 1. characterising the complex characteristics of AD of critically
      ill MODS patients by the nonlinear parameters of autonomic information flow
      (AIF), 2. comparing AIF with autonomic function of healthy controls, and 3.
      characterising the accuracy of this parameter in predicting mortality in MODS.
      METHODS: We enrolled 43 score-defined MODS patients who were consecutively
      admitted to a twelve-bed medical intensive care unit in a university centre into
      this prospective outcome study. Additionally, we assigned 50 healthy controls to
      the study. AIF was assessed as a complexity function of AD using 24-h ECG.
      Measures of AIF were introduced according to the standard HRV concept. The
      patients were followed up for 28-day mortality. RESULTS: MODS causes a
      disorganisation of short term AIF in favour of an enhanced (rigid) long term AIF.
      Concerning prognosis increased short term AIF was associated with survival. Short
      term AIF discriminated between MODS survivors and non-survivors at the level of
      APACHE II score. CONCLUSIONS: This is the first study providing evidence that
      complex AD of MODS patients is specifically assessed by AIF time scales and that
      AIF has significant prognostic impact.

PMID- 15979172
TI  - Discrimination between physiologic and pathologic left ventricular dilatation.
AB  - The identification of certain cardiovascular disease in athletes may constitute
      the basis for disqualification from competition in an effort to minimize the risk
      of sudden cardiac death. The aim of this study was to assess diastolic and
      systolic parameters measured by tissue Doppler imaging in endurance veteran
      athletes who had prominent cardiac dilatation and patients with idiopathic
      dilated cardiomyopathy in order to determine whether these variables might
      differentiate each other.

PMID- 15979173
TI  - Investigations of cattle herd breakdowns with bovine tuberculosis in four
      counties of England and Wales using VETNET data.
AB  - Cattle herd breakdown (HBR) with bovine tuberculosis (BTB) was investigated for
      farms in four counties of England and Wales outside southwest England from 1986
      to early 2000. Data from the national database of TB testing history (VETNET)
      were used. Factors that influenced HBR included calendar time, herd size, number
      of cattle tested, the test type, the inter-test interval and spatial grouping of
      farms. Herd tests other than routine herd tests had an increased risk of HBR in
      all four counties. In all counties, the risk of HBR increased with calendar time
      and in Shropshire a test interval of 3 years was associated with an increased
      risk of HBR compared with a 1-year test interval. In Staffordshire and Sussex, a
      4-year test interval was associated with a lower risk of HBR compared with a 1
      year test interval. There was no evidence of spatial clustering of HBR in West
      Glamorgan (equal spatial risk in a 15-30 km radius) and weak evidence of spatial
      clustering in Shropshire (7-15 km) and Sussex (5-10 km). In Staffordshire, there
      was evidence of spatial (2-4 km) and time (3-4 years) clustering of HBR. The
      locally increased rate of testing following a confirmed HBR increased the
      detection of infected herds but did not prevent local spread in two of the four
      counties (Shropshire and Staffordshire) since the rate of HBR increased linearly
      from 1988 to 2000. The main conclusion is that there were both local and distant
      components of spread.

PMID- 15979174
TI  - Enhancement of protein synthesis by an inorganic polyphosphate in an E. coli cell
      free system.
AB  - In an E. coli cell-free protein synthesis system, the addition of an inorganic
      polyphosphate [poly(P)] with polyphosphate:AMP phosphotransferase (PAP), which
      regenerates AMP to ADP, increased the amount of protein synthesis. The maximum
      yield of the translation product (green fluorescent protein) in the E. coli cell
      free system provided by Roche Diagnostics (RTS-100) was 1.16 mg/ml under the
      optimum reaction condition, which corresponded to a 5.7-fold of that obtained
      under the standard reaction condition described in the manufacturer's protocol.
      Interestingly, poly(P) alone enhanced protein synthesis to some extent. When we
      added poly(P) to the reaction mixture, ATP was consumed at a faster rate, leading
      to a rapid accumulation of AMP. By adding both poly(P) and PAP to the reaction
      mixture, an efficient ATP regeneration reaction derived from AMP occurred and the
      ATP level was recovered. Since the protein synthesis enhancement by poly(P) was
      also observed when mRNA was added as the template in the reaction, poly(P)
      accelerated the translation reaction by directly affecting the translation
      machinery. This also occurred when we used the Pure-system Classic Mini kit (Post
      Genome Institute) that contained the minimum requirements (pure enzymes and
      chemicals) for translation and transcription. We also observed that poly(P)
      extended the half-life of the mRNA template.

PMID- 15979175
TI  - FISH and chips: marine bacterial communities analyzed by flow cytometry based on
      microfluidics.
AB  - To unveil the structure of natural marine pelagic bacterial communities, PCR
      based techniques as well as fluorescence in situ hybridizations (FISH) were
      successfully performed in the past. Using fluorescence microscopes or confocal
      laser scanning microscopes (CLSM) for the analysis of FISH experiments, it was
      possible to differentiate bacterial communities, but most attempts to combine
      flow cytometry and FISH for this purpose have failed till now. Here we present a
      successful analysis of FISH experiments of natural marine pelagic bacterial
      communities using a flow cytometer based on microfluidics (Agilent 2100
      bioanalyzer). Marine water samples were enriched on polycarbonate filters and
      hybridized with Cy5 labeled gene probes of different phylogenetic depth. Bacteria
      were detached from the filters and subsequently analyzed in the Cell Chip of the
      Agilent 2100 Bioanalyzer. Samples were counter-stained using SYTOX. In all
      samples the EUB338 positive signals could be clearly differentiated from those of
      the NON probe. Furthermore a dominance of alpha-protebacteria (as indicated by
      the probes ALF968 and G rB) could be observed. Microfluidics based flow cytometry
      is a promising technique for the analysis of natural bacterial communities from
      the marine environment.

PMID- 15979176
TI  - Use of the modified robbins device and fluorescent staining to screen plant
      extracts for the inhibition of S. mutans biofilm formation.
AB  - Streptococcus mutans plays an important role in the formation of dental plaque.
      To study biofilm growth on hydroxyapatite (HA) in vitro, a flow system based on a
      Modified Robbins Device (MRD) and a method for the quantification of the biomass
      using fluorescent staining with SYTO(R) 9 were developed. The combined approach
      was used to assess the inhibitory effect of plant extracts on biofilm formation
      in concentrations below their minimal inhibitory concentrations.

PMID- 15979177
TI  - PA 20, a semi-selective medium for isolation and enumeration of Pantoea ananatis.
AB  - A semi-selective medium, PA 20, was developed for the isolation and enumeration
      of Pantoea ananatis from plant material, specifically from onion seed. The medium
      has a pH of 8.0 and contains NH4H2PO4, K2HPO4, magnesium sulphate, NaCl, d (+)
      arabitol, crystal violet, bromothymol blue and thallium nitrate. All P. ananatis
      strains from a variety of hosts produced characteristic yellow colonies in 6-7
      days at 25 degrees C. Plating efficiencies on PA 20 in comparison to nutrient
      agar ranged from 92 to 112%. Recovery from naturally infested and artificially
      contaminated onion seed was high, with an almost total reduction of saprophytes.

PMID- 15979178
TI  - Effects of biotechnology on biodiversity: herbicide-tolerant and insect-resistant
      GM crops.
AB  - Biodiversity is threatened by agriculture as a whole, and particularly also by
      traditional methods of agriculture. Knowledge-based agriculture, including GM
      crops, can reduce this threat in the future. The introduction of no-tillage
      practices, which are beneficial for soil fertility, has been encouraged by the
      rapid spread of herbicide-tolerant soybeans in the USA. The replacement of
      pesticides through Bt crops is advantageous for the non-target insect fauna in
      test-fields. The results of the British Farm Scale experiment are discussed.
      Biodiversity differences can mainly be referred to as differences in herbicide
      application management.

PMID- 15979179
TI  - The best control for the specificity of RNAi.
AB  - RNA interference (RNAi) is revolutionizing functional genomics. However, there
      are several reasons to be concerned about the specificity and off-target effects
      of this technique. A recent paper by Kittler et al. describes a straightforward
      way to validate RNAi specificity, which exploits the increasing availability of
      bacterial artificial chromosome (BAC) clone resources. Genetic rescue of the RNAi
      phenotype by BAC transgenesis is the best control yet described for specificity,
      and has further implications for reverse genetics.

PMID- 15979180
TI  - Prediction of pathogen growth on iceberg lettuce under real temperature history
      during distribution from farm to table.
AB  - The growth of pathogenic bacteria Escherichia coli O157:H7, Salmonella spp., and
      Listeria monocytogenes on iceberg lettuce under constant and fluctuating
      temperatures was modelled in order to estimate the microbial safety of this
      vegetable during distribution from the farm to the table. Firstly, we examined
      pathogen growth on lettuce at constant temperatures, ranging from 5 to 25 degrees
      C, and then we obtained the growth kinetic parameters (lag time, maximum growth
      rate (micro(max)), and maximum population density (MPD)) using the Baranyi
      primary growth model. The parameters were similar to those predicted by the
      pathogen modelling program (PMP), with the exception of MPD. The MPD of each
      pathogen on lettuce was 2-4 log(10) CFU/g lower than that predicted by PMP.
      Furthermore, the MPD of pathogens decreased with decreasing temperature. The
      relationship between mu(max) and temperature was linear in accordance with
      Ratkowsky secondary model as was the relationship between the MPD and
      temperature. Predictions of pathogen growth under fluctuating temperature used
      the Baranyi primary microbial growth model along with the Ratkowsky secondary
      model and MPD equation. The fluctuating temperature profile used in this study
      was the real temperature history measured during distribution from the field at
      harvesting to the retail store. Overall predictions for each pathogen agreed well
      with observed viable counts in most cases. The bias and root mean square error
      (RMSE) of the prediction were small. The prediction in which mu(max) was based on
      PMP showed a trend of overestimation relative to prediction based on lettuce.
      However, the prediction concerning E. coli O157:H7 and Salmonella spp. on lettuce
      greatly overestimated growth in the case of a temperature history starting
      relatively high, such as 25 degrees C for 5 h. In contrast, the overall
      prediction of L. monocytogenes under the same circumstances agreed with the
      observed data.

PMID- 15979181
TI  - An outbreak of food-borne listeriosis due to cheese in Japan, during 2001.
AB  - Food-borne outbreaks caused by Listeria monocytogenes have been recognized in US
      and European countries. Only sporadic cases, of neonatal listeriosis, have been
      reported in Japan. Since L. monocytogenes has been often isolated from foods in
      Japan, food-borne outbreaks potentially could have occurred. In February 2001, L.
      monocytogenes serotype 1/2b was isolated from a washed-type cheese during routine
      Listeria monitoring of 123 domestic cheeses. Further samples from products and
      the environments at the plant that produced the contaminated cheese were examined
      for L. monocytogenes. L. monocytogenes serotype 1/2b was detected in 15 cheese
      samples, at most probable number that ranged from <30 to 4.6 x 10(9)/100 g, and
      in environmental samples. Studies with people who had consumed cheese from the
      plant revealed 86 persons who had been infected with L. monocytogenes. Thirty
      eight of those people had developed clinical symptoms of gastroenteritis or the
      common cold type after the consumption of cheese. Isolates from those patients
      exhibited the same serotype, pathogenicity for mice and HeLa cells, DNA
      fingerprinting patterns and PCR amplification patterns. From the epidemiological
      and genetic evidence, it appeared that the outbreak was caused by cheese. This is
      the first documented incidence of food-borne listeriosis in Japan.

PMID- 15979182
TI  - Influence of temperature and pH on Saccharomyces bayanus var. uvarum growth;
      impact of a wine yeast interspecific hybridization on these parameters.
AB  - The species Saccharomyces bayanus var. uvarum possesses interesting enological
      characteristics but produces high concentration of volatile fermentative
      compounds not desirable in Sauvignon blanc wines. Interspecific hybrids between
      Saccharomyces cerevisiae and S. bayanus var. uvarum were made in order to join
      the main parental advantages. Two hybrids were selected on the basis of their
      fermentation characteristics and their karyotypes, i.e. they have a different
      mitochondrial DNA. In order to produce these hybrids as active dry yeast to be
      used as starter in wine-making, their optimal environmental conditions for
      growth, i.e. temperature and pH, were determined as the objective of our work.
      Using a two-level factorial design it was found that the two parental strains
      have different optimal temperature but for the two strains, pH does not have a
      significant influence on growth. The influence of temperature on biomass
      productivity for hybrid strains were strictly identical, so we suppose that the
      main genes coding for temperature sensitivity were not contained in mitochondrial
      DNA, but in nuclear DNA. Moreover the reactions of hybrid strains to the
      temperature variations were similar to the one of S. bayanus var. uvarum. This
      latter strain could have a majority of genes responsible of temperature
      sensitivity dominant in comparison with those of the strain S. cerevisiae.

PMID- 15979183
TI  - Characterization of Lactobacillus strains and monitoring by RAPD-PCR in
      controlled fermentations of "Almagro" eggplants.
AB  - The characterization of 23 Lactobacillus strains was performed. The strains were
      assayed for biogenic amine-forming capacity, hydrogen peroxide production, pectin
      esterase, cellulase and polygalacturonase production, growth rate, acidifying
      capacity and salt tolerance. Three strains were selected which belonged to the
      species, Lactobacillus brevis, Lactobacillus plantarum and Lactobacillus
      fermentum. Different starter cultures prepared as combinations of these three
      strains were assayed in pilot scale fermentations and Randomly Amplified
      Polymorphic DNA (RAPD) analysis, using a previously selected random primer, was
      applied for monitoring the inoculated strains. The course of fermentations was
      similar in all batches but sensorial analysis of eggplants fermented using a
      mixed culture of the three strains displayed the best results, and no differences
      were obtained when compared with commercial eggplants.

PMID- 15979184
TI  - Dietary exposure to aflatoxin from maize and groundnut in young children from
      Benin and Togo, West Africa.
AB  - Aflatoxins are a family of fungal toxins that are carcinogenic to man and cause
      immunosuppression, cancer and growth reduction in animals. We conducted a cross
      sectional study among 480 children (age 9 months to 5 years) across 4 agro
      ecological zones (SS, NGS, SGS and CS) in Benin and Togo to identify the effect
      of aflatoxin exposure on child growth and assess the pattern of exposure. Prior
      reports on this study [Gong, Y.Y.,Cardwell, K., Hounsa, A., Egal, S., Turner,
      Hall, A.J., Wild, C.P., 2002. Dietary aflatoxin exposure and impaired growth in
      young children from Benin and Togo: cross sectional study. British Medical
      Journal 325, 20-21, Gong, Y.Y., Egal, S., Hounsa, A., Turner, P.C., Hall, A.J.,
      Cardwell, K., Wild, C.P., 2003. Determinants of aflatoxin exposure in young
      children from Benin and Togo, West Africa: the critical role of weaning and
      weaning foods. International Journal of Epidemiology, 32, 556-562] showed that
      aflatoxin exposure among these children is widespread (99%) and that growth
      faltering is associated with high blood aflatoxin-albumin adducts (AF-alb
      adducts), a measure of recent past exposure. The present report demonstrates that
      consumption of maize is an important source of aflatoxin exposure for the survey
      population. Higher AF-alb adducts were correlated with higher A. flavus (CFU)
      infestation of maize (p=0.006), higher aflatoxin contamination (ppb) of maize
      (p<0.0001) and higher consumption frequencies of maize (p=0.053). The likelihood
      of aflatoxin exposure from maize was particularly high in agro-ecological zones
      where the frequency of maize consumption (SGS and CS), the presence of aflatoxin
      in maize (SGS) or the presence of A. flavus on maize (NGS and SGS) was relatively
      high. Socio-economic background did not affect the presence of A. flavus and
      aflatoxin in maize, but better maternal education was associated with lower
      frequencies of maize consumption among children from the northernmost agro
      ecological zone (SS) (p=0.001). The impact of groundnut consumption on aflatoxin
      exposure was limited in this population. High AF-alb adduct levels were
      correlated with high prevalence of A. flavus and aflatoxin in groundnut, but
      significance was weak after adjustment for weaning status, agro-ecological zone
      and maternal socio-economic status (resp. p=0.091 and p=0.083). Ingestion of A.
      flavus and aflatoxin was high in certain agro-ecological zones (SS and SGS) and
      among the higher socio-economic strata due to higher frequencies of groundnut
      consumption. Contamination of groundnuts was similar across socio-economic and
      agro-ecological boundaries. In conclusion, dietary exposure to aflatoxin from
      groundnut was less than from maize in young children from Benin and Togo.
      Intervention strategies that aim to reduce dietary exposure in this population
      need to focus on maize consumption in particular, but they should not ignore
      consumption of groundnuts.

PMID- 15979185
TI  - Growth of lactic acid bacteria and Rhizopus oligosporus during barley tempeh
      fermentation.
AB  - The zygomycete Rhizopus oligosporus is traditionally used to ferment soybean
      tempeh, but it is also possible to ferment other legumes and cereals to tempeh.
      The traditional soybean tempeh harbours a multitude of microorganisms with
      potentially beneficial or detrimental effects on quality. Lactic acid bacteria
      (LAB) have positive effects on the safety of soybean tempeh, but the effects of
      LAB on R. oligosporus growth have not been investigated. We have developed a
      cereal grain tempeh by fermenting pearled barley with R. oligosporus ATCC 64063.
      Four LAB species, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus
      reuteri and Lactococcus lactis were assessed for their growth abilities and their
      effects on R. oligosporus growth during barley tempeh fermentation. Growth of LAB
      was assayed as colony forming units (cfu), while growth of R. oligosporus was
      measured as ergosterol content and hyphal length. The two fungal measurements
      highly correlated (r=0.83, P<0.001, n=90). The ergosterol content of fungal
      mycelia ranged from 11.7 to 30.1 mg/g fungal dry matter. L. plantarum multiplied
      from 4.8 to 7.4 log cfu/g dry tempeh and L. fermentum increased from 4.4 to 6.8
      log cfu/g during 24 h incubation at 35 degrees C. L. reuteri and L. lactis had
      significantly slower growth, with increases from 4.8 to 5.6 log cfu/g and 5.0 to
      5.4 log cfu/g, respectively. The growth of R. oligosporus and the final pH (4.9)
      in barley tempeh were not significantly influenced by any of the LAB
      investigated.

PMID- 15979186
TI  - Coral red fluorescence protein as genetic modified baculovirus tracer.
AB  - Genetic modified baculovirus (GMBV) are among the most promising alternatives to
      chemical insecticides. One of the deterrents to the GMBV development is the lack
      of simple and cost-effective methods for monitoring their efficacy and ecology in
      fields. Here, we demonstrate the DsRed gene from coral can serve as a convenient
      GMBV tracer. Insect larvae, including Trichoplusia ni, Spodoptera exigua, and
      Spodoptera litura, infected the GMBV containing the DsRed gene can emit red
      fluorescence under sun light without any prosthetic apparatus.

PMID- 15979187
TI  - Cisplatin delivery from poly(acrylic acid-co-methyl methacrylate) microparticles.
AB  - To develop a platform for tumor chemotherapy, poly(acrylic acid-co-methyl
      methacrylate) microparticles have been synthesized. Carboxylate containing
      monomers were included to complex therapeutic agents, specifically cisplatin.
      Microparticles were prepared by free radical emulsion polymerization in aqueous
      media. Particle diameter, zeta-potential, in vitro cytotoxicity, and in vivo
      acute toxicity were characterized for both cisplatin-loaded microparticles and
      unloaded microparticles. In vitro cytotoxicity and FT-IR were used to
      characterize cisplatin released from cisplatin-loaded microparticles. Acrylic
      acid feed mole fraction determined several key microparticle properties,
      including particle size, zeta-potential, and yield. A burst release of cisplatin
      (40%) in the first day was followed by a zero-order release phase. The
      interaction between cisplatin and microparticles allowed approximately 20%
      additional cisplatin release in the next five days. Cisplatin-loaded and unloaded
      microparticles are non-toxic (LC50>15 mM) to the cell line used in in vitro
      tests. Cisplatin released from cisplatin-loaded microparticles retained activity,
      but that activity was slightly lower than freshly prepared cisplatin. Other than
      a slight reduction in cisplatin activity, microparticles exhibited low in vivo
      acute toxicity (LD50>170 mg/kg), which suggests that this hydrogel particulate
      system and the hydrogel complexation mechanism should further be studied for drug
      delivery.

PMID- 15979189
TI  - Development and in vitro evaluation of a liposomal vaginal delivery system for
      acyclovir.
AB  - Design of a liposome delivery system for vaginal administration of acyclovir,
      able to provide sustained release and improved bioavailability of the
      encapsulated drug for the local treatment of genital herpes was investigated.
      Acyclovir was encapsulated in liposomes prepared by the polyol dilution method,
      whereby various phospholipid compositions were used: egg phosphatidylcholin
      (PC)/egg phosphatidylglycerol (PG) 9:1, egg phosphatidylcholine (PC) and egg
      phosphatidycholine (PC)/stearylamine (SA) 9:3. All liposome preparations were
      characterized and compared for particle size, polydispersity, encapsulation
      efficiency and tested for in vitro stability in different media chosen to
      simulate human vaginal conditions: buffer, pH 4.5 (corresponding to normal human
      vaginal pH), vaginal fluid simulant (medium developed so as to mimic the fluid
      produced in the vagina) with or without mucin. To be closer to in vivo
      application of liposomes and to achieve further improvement of their stability,
      liposomes were incorporated in a vehicle suitable for vaginal self
      administration. Bioadhesive hydrogel made from Carbopol 974P NF resin with
      adequate pH value and desirable viscosity was chosen as a vehicle for liposomes
      containing acyclovir. In vitro release studies of liposomes incorporated in the
      hydrogel proved their applicability as a novel vaginal delivery system with
      localized and sustained release of encapsulated acyclovir. Even after 24 h of
      incubation in vaginal fluid simulant more than 35% of the originally encapsulated
      drug was retained in the hydrogel.

PMID- 15979188
TI  - Multilayered polyelectrolyte films promote the direct and localized delivery of
      DNA to cells.
AB  - Multilayered polyelectrolyte films fabricated from plasmid DNA and a
      hydrolytically degradable synthetic polycation can be used to direct the
      localized transfection of cells without the aid of a secondary transfection
      agent. Multilayered assemblies 100 nm thick consisting of alternating layers of
      synthetic polymer and plasmid DNA encoding for enhanced green fluorescent protein
      (EGFP) were deposited on quartz substrates using a layer-by-layer fabrication
      procedure. The placement of film-coated slides in contact with COS-7 cells
      growing in serum-containing culture medium resulted in gene expression in cells
      localized under the film-coated portion of the slides. The average percentage of
      cells expressing EGFP relative to the total number of cells ranged from 4.6% to
      37.9%, with an average of 18.6%+/-8.2%, as determined by fluorescence microscopy.
      In addition to providing a mechanism for the immobilization of DNA at the
      cell/surface interface, a preliminary analysis of film topography by atomic force
      microscopy (AFM) demonstrated that polymer /DNA films undergo significant
      structural rearrangements upon incubation to present surface bound condensed
      plasmid DNA nanoparticles. These data suggest that the presence of the cationic
      polymer in these materials may also contribute to the internalization and
      expression of plasmid. The materials and design principles reported here present
      an attractive framework for the local or non-invasive delivery of DNA from the
      surfaces of implantable materials or biomedical devices.

PMID- 15979190
TI  - Cytosolic delivery of macromolecules 4. Head group-dependent membrane
      permeabilization by pH-sensitive detergents.
AB  - Three tertiary amine-based detergents with zero, one, or two hydroxyl groups at
      various positions in their head group were characterized for their ability to
      promote the cytosolic delivery of macromolecules. Critical micellar
      concentrations (CMC) and membrane-bound pKa values of the lipid constructs
      increased with increasing head group polarity, ranging from 1-5 microM and 5.9 to
      6.3, respectively. Fluorescence resonance energy transfer (FRET) and calcein
      leakage experiments revealed that when the amine group is protonated introduction
      of -OH moieties to detergent head groups enhanced their ability to interact with
      and permeabilize anionic, endosome-mimicking vesicles. Different formulations of
      a diethanolamine-based lipid (DEL) were further evaluated for pH-dependent
      hemolytic activity and ability to promote cytosolic delivery of macromolecules in
      vitro. Intact liposomes containing DEL at its maximum limit of incorporation were
      less efficient than DEL-containing micelles in promoting hemoglobin leakage from
      human erythrocytes at acidic pH. In HeLa cells, DEL-containing detergent micelles
      facilitated efficient cytosolic release of endocytosed macromolecules such as
      fluorescein-labeled dextran of MW 10 kDa. This observation was further
      corroborated by a functional assay based on antisense-mediated up-regulation of
      enhanced green fluorescent protein (EGFP). Taken together, our findings emphasize
      the key role of polar head groups and micellar architecture of pH-sensitive
      detergents in mediating endosomal permeabilization and the efficient cytosolic
      delivery of macromolecules.

PMID- 15979191
TI  - Transporting silence: design of carriers for siRNA to angiogenic endothelium.
AB  - The recently developed siRNA oligonucleotides are an attractive alternative to
      antisense as a therapeutic modality because of their robust, gene selective
      silencing of drug target protein expression. To achieve therapeutic success,
      however, several hurdles must be overcome including rapid clearance, nuclease
      degradation, and inefficient intracellular localization. In this presentation, we
      discuss design strategies for development of self-assembling nanoscale carriers
      for neovasculature targeted delivery of siRNA inhibiting tumor or ocular
      angiogenesis.

PMID- 15979192
TI  - [A comparative study of fibromyalgia treatment: ultrasonography and physiotherapy
      versus sertraline treatment].
AB  - OBJECTIVE: To compare the efficacy of sertraline versus physical therapy
      (ultrasonography and physical therapy) in fibromyalgia. DESIGN: A 6-month
      comparative, prospective, randomised study of 70 female patients, aged 42 to 52,
      with fibromyalgia according to the criteria of the American College of
      Rheumatology. One group (N=36) underwent 6-month treatment with sertraline, 50
      mg/24 h. The other group (N=34) received 15 sessions of 1 W/cm2 ultrasonography
      on the cervical trigger points plus physical therapy. Variables analyzed on a
      visual 10-point scale were pain and morning stiffness and sleep disorders by use
      of the sleep questionnaire of the Medical Outcome Study (MOS). Measurements were
      taken at the beginning of the study and at 3-month and 6-month follow-up.
      RESULTS: Pain significantly diminished in the sertraline group during the entire
      study (visual numeric scale: 7.2+/-1.1 initially, 5.3+/-?? at 3 months and 3+/
      0.7 at 6 months, P<0.05). Morning stiffness and sleep disorder scores were
      positive only for the sertraline group during the entire 6 months (P<0.05).
      Results from the MOS questionnaire showed improvement only for the sertraline
      group. Of the Sertraline group, 83% evaluated the treatment as good or very good,
      as compared with only 6% of the ultrasonography group. No patient withdrew from
      the study. CONCLUSION: Patients treated with sertraline had a better outcome in
      terms of pain, morning stiffness and sleep disorders, than the group treated with
      ultrasonography and physical therapy.

PMID- 15979193
TI  - Household health-seeking behaviour in Khartoum, Sudan: the willingness to pay for
      public health services if these services are of good quality.
AB  - In this paper, we analyse the extent of willingness to pay for good quality
      public health services in relation to the demographic and socio-economic
      characteristics of respondents. The analysis was carried out by way of a
      household survey conducted in Khartoum, Sudan in 2001. We studied willingness to
      pay by means of a contingent valuation method. A logistic regression model was
      used for the statistical analysis. The results show that the overall percentage
      of people who are willing to pay for good quality public health services is
      either 80% or 75% depending on whether respondents already pay for these services
      (group 1) or not (group 2). They show that although the two groups are willing to
      pay for good quality public health services, the demographic characteristics that
      affect the willingness to pay differ between the two groups. The results of the
      logistic regression analysis for each group are remarkably similar. We conclude
      that if the quality of services is improved, reasonable fees could be set. This
      supports the continuity of the policy to recover costs because virtually the
      majority of the households would be willing to pay reasonable fees.

PMID- 15979195
TI  - Striking nucleotide frequency pattern at the borders of highly conserved
      vertebrate non-coding sequences.
AB  - In a recent study, 1373 highly conserved non-coding elements (CNEs) were detected
      by aligning the human and Takifugu rubripes (Fugu) genomes. The remarkable degree
      of sequence conservation in CNEs compared with their surroundings suggested
      comparing the base composition within CNEs with their 5' and 3' flanking regions.
      The analysis reveals a novel, sharp and distinct signal of nucleotide frequency
      bias precisely at the border between CNEs and flanking regions.

PMID- 15979194
TI  - RNA interference and heterochromatin in the fission yeast Schizosaccharomyces
      pombe.
AB  - Fission yeast is a useful model for RNA interference because it has single-copy
      genes for components of the RNAi pathway such as argonaute, dicer and RNA
      dependent RNA polymerase (RdRP). Functions for RNAi revealed in S. pombe, such as
      heterochromatic silencing and chromosome segregation, are likely to be ancient
      because they are shared with some other eukaryotes. The underlying mechanisms are
      being rapidly unraveled.

PMID- 15979196
TI  - Issues in the analysis of oligonucleotide tiling microarrays for transcript
      mapping.
AB  - Traditional microarrays use probes complementary to known genes to quantitate the
      differential gene expression between two or more conditions. Genomic tiling
      microarray experiments differ in that probes that span a genomic region at
      regular intervals are used to detect the presence or absence of transcription.
      This difference means the same sets of biases and the methods for addressing them
      are unlikely to be relevant to both types of experiment. We introduce the
      informatics challenges arising in the analysis of tiling microarray experiments
      as open problems to the scientific community and present initial approaches for
      the analysis of this nascent technology.

PMID- 15979197
TI  - Distribution kinetics of 18F-DOPA in weaver mutant mice.
AB  - Distribution kinetics of 18F-fluoro-dihydroxy phenylalanine (18F-DOPA) were
      studied with high-resolution micro-positron emission tomography (microPET)
      imaging and conventional methods in control wild-type mice, heterozygous weaver
      mutant mice, and homozygous weaver mutant mice. 18F-DOPA uptake was significantly
      increased in the CNS within 60 min in all the genotypes examined. Homozygous
      weaver mutant mice exhibited significantly reduced 18F-DOPA uptake in the region
      of interest (striatum) as compared to heterozygous weaver mutant mice and control
      wild-type mice. 18F-DOPA was de-localized in the kidneys of homozygous weaver
      mutant mice. The radioactivity was localized primarily in the liver and kidneys
      within 2 h and in the urinary bladder within 4 h. After 8 h, it could be detected
      neither by conventional nor by microPET imaging. Distribution kinetics of 18F
      DOPA with microPET imaging correlated and confirmed the conventional
      observations. These data are interpreted to suggest that microPET imaging may
      provide an efficient, noninvasive, cost-effective procedure to study distribution
      kinetics of PET radiopharmaceuticals in rare genetically altered animals.
      Furthermore, this unique and noninvasive approach may expedite quality control
      and drug development for human applications.

PMID- 15979198
TI  - Transcriptional regulation of ceruloplasmin by an IL-6 response element pathway.
AB  - Cp is an acute phase reactant protein that also acts as a ferroxidase, and thus
      indirectly decreases the production of the reactive oxygen species hydroxyl
      radical. Ceruloplasmin (Cp) expression is induced by a variety of central nervous
      system injuries, but the mechanism by which this occurs is unclear. Based on the
      fact that peripheral nerve injury induces interleukin-6 (IL-6) expression and
      that there are three IL-6 response elements in the upstream region of the Cp
      gene, we studied their role in transcriptional regulation of Cp in astrocytic C6
      glioma cells, using transfection of a rat Cp-luciferase construct, followed by
      sequential and simultaneous mutation of the IL-6 response elements. We found that
      0.8 kb of sequence upstream to the rat ceruloplasmin start site was sufficient to
      drive luciferase expression in C6 glioma cells. Cells transfected with Cp-luc and
      treated with 100 ng/ml rat IL-6 induced 216.8% +/- 4.6% of control activity.
      Mutagenesis of the IL-6 response elements decreased luciferase activity, with the
      maximal decline (9.7 +/- 0.7% of wild-type) after mutation of the second site.
      Mutagenesis of multiple sites decreased activity beyond mutagenesis of single
      sites with mutation of all three sites decreasing activity to 5.3 +/- 0.4% of
      wild-type. Gel shift and supershift assays indicated that activation of Cp in
      these cells was not via STAT-3. These results are consistent with a signaling
      process via IL-6 response elements for Cp upregulation.

PMID- 15979199
TI  - Natural expression of immature Ucn antisense RNA in the rat brain. Evidence
      favoring bidirectional transcription of the Ucn gene locus.
AB  - Recently, it has been shown the endogenous expression of an antisense urocortin
      (Ucn) transcript in the rat brain and other tissues. In the present work, by
      means of two complementary techniques, specific-strand RT-PCR and in situ
      hybridization, we showed the natural expression of a second novel antisense Ucn
      RNA of higher size. Specific-strand RT-PCR of total RNA, cloning and sequence
      analysis together with the different subcellular localization observed for both
      antisense Ucn RNAs indicated that this novel antisense Ucn transcript
      corresponded to the immature form of the previously described antisense Ucn RNA.
      Sequence analysis indicated that this immature antisense Ucn transcript uses non
      consensus CT-AC splice sites, exactly complementary to its sense counterpart. The
      mature antisense Ucn transcript was also amplified after specific-strand RT-PCR
      of poly(A)-RNA, suggesting that the mature antisense Ucn transcript is
      polyadenylated. We also proved that the region complementary to the promoter of
      sense Ucn RNA, including the TATA box, is part of the antisense Ucn RNA. Finally,
      we showed that the region complementary to the 3'-end of Ucn mRNA behaves as a
      functional promoter for the transcription of antisense Ucn RNA. Thus, the results
      indicate that the 3'-ends of both sense and antisense Ucn RNAs are the only non
      complementary sequences between them. In conclusion, the present findings suggest
      that the Ucn gene locus naturally undergoes bidirectional transcription yielding
      a sense and an antisense RNA expanding the spectrum of antisense RNAs originated
      from the same genomic loci to antisense transcripts that are spliced using these
      non-consensus CT-AC splice sites.

PMID- 15979200
TI  - Tissue expression of alternatively spliced GFRalpha1, NCAM and RET isoforms and
      the distinct functional consequence of ligand-induced activation of GFRalpha1
      isoforms.
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) exerts its effect through a
      multi-component receptor system consisting of GFRalpha1, RET and NCAM. Two highly
      homologous alternatively spliced GFRalpha1 isoforms (GFRalpha1a and GFRalpha1b)
      have previously been identified. In this study, isoform specific real-time PCR
      assays were used to quantify the expression levels of GFRalpha1, RET and NCAM
      isoforms in murine embryonic and adult tissues. The expression levels of
      GFRalpha1b were found to be comparable to that of GFRalpha1a in peripheral
      tissues. However, GFRalpha1a was the predominant isoform expressed in the whole
      brain. The co-expressions of GFRalpha1 and the co-receptors were developmentally
      regulated and differentially expressed in some tissues. Microarray analyses of
      GFRalpha1 isoforms transfected cells stimulated with NTN showed distinct and non
      overlapping gene profiles. These observations are consistent with the emerging
      view that the combinatorial interactions of the spliced isoforms of GFRalpha, RET
      and NCAM may contribute to the pleiotropic biological responses.

PMID- 15979201
TI  - Disputing taste: foods pleasure as an achievement in interaction.
AB  - While identity has been a dominant topic in research on food choice, literature
      on identity in consumers' everyday life is scarce. In this article we draw on
      insights from discursive psychology to demonstrate how members of an online forum
      on food pleasure handle the hedonic appreciation of food in everyday interaction.
      We examined 40 discussions consisting of 1715 e-mails related to culinary topics.
      The analysis focuses on the way in which the participants of this forum work up
      and establish their identities as 'gourmets'. A dominant tool in performing this
      identity work is the discursive construction of independent access to knowledge
      of and experience with food items, so as to compete with or resist the epistemic
      superiority of a preceding evaluation. Data are presented with nine examples of
      the 73 manifestations of the construction of independent access. Contrary to
      sensory approaches to food choice, this study depicts the enjoyment of food as an
      interactional achievement rather than a pure physiological sensation. Wider
      implications of this study for the relation between food, identity and taste are
      discussed.

PMID- 15979202
TI  - Worldwide polymorphism at the MC1R locus and normal pigmentation variation in
      humans.
AB  - While there have been many advances in our understanding of the genetics of
      pathological skin pigmentation in humans, our knowledge about what determines
      variation in normal skin color is still incomplete. Variation in one gene,
      melanocortin 1 receptor (MC1R), has been associated with red hair and fair skin
      in Europeans. However, this gene might also play an important role in shaping
      pigmentation of other human populations, where it experiences different selective
      pressures. Below we review what is currently known about polymorphism and
      selection at the MC1R coding and promoter regions in human populations, the
      pattern of MC1R evolution in nonhuman primates, and the interaction of MC1R with
      other genes.

PMID- 15979204
TI  - Involvement of melanocortin-4 receptor in anxiety and depression.
AB  - The melanocortins, which are derived from proopiomelanocortin, have a variety of
      physiological functions mediated membrane surface receptors. To date, five
      subtypes have been cloned. With the cloning of melanocortin receptors, studies
      with genetic models, and development of selective compounds, the physiological
      roles of the five melanocortin receptors have begun to be understood. The
      melanocortin-4 receptor (MC4R), which is predominantly expressed in the central
      nervous system, has in particular become the focus of much attention in recent
      years because of the critical roles it plays in a wide range of functions,
      including feeding, sexual behavior, and stress. Recent development of selective
      antagonists for the MC4R has provided pharmacological evidence that blockade of
      MC4R could be a useful way of alleviating numerous conditions such as
      anxiety/depression, pain, and addiction to drugs of abuse.

PMID- 15979203
TI  - Histatin and lactoferrin derived peptides: antimicrobial properties and effects
      on mammalian cells.
AB  - In order to analyze the clinical potential of two antimicrobial peptides, human
      lactoferrin 1-11 (hLF1-11) and synthetic histatin analogue Dhvar-5, we measured
      the killing effect on bacteria, and the potential toxicity on erythrocytes and
      bone cells. The antimicrobial activity was determined in a killing assay on six
      strains, including methicillin resistant Staphylococcus Aureus. The effect on
      human erythrocytes and MC3T3 mouse bone cells was measured with a hemolysis assay
      and a viability assay, respectively. Both hLF1-11 and Dhvar-5 dose-dependently
      killed all bacterial strains, starting at concentrations of 6 microg/mL. hLF1-11
      had no effect on mammalian cells at concentrations up to 400 microg/mL, but Dhvar
      5 induced significant hemolysis (37% at 200 microg/mL) and bone cell death (70%
      at 400 microg/mL). This indicates that both peptides are able to kill various
      resistant and non-resistant bacteria, but Dhvar-5 may exert a cytotoxic effect on
      host cells at higher concentrations.

PMID- 15979205
TI  - Gene polymorphisms and their effects in the melanocortin system.
AB  - In addition to its role in human pigmentation, components of the melanocortin
      system regulate appetite, energy homeostasis and hormone production. Recent
      studies have suggested possible roles of this system in immunity, transmission of
      pain signals, and reproductive potential. A number of polymorphisms have been
      identified in genes of the melanocortin system and are associated with
      pigmentation in humans, as well as being causative of disorders of adrenal
      hormone production and obesity. This review gives an outline of these
      polymorphisms, their functional significance and possible application to or
      impact on diagnosis and pharmacotherapy based on melanocortin pathways.

PMID- 15979206
TI  - High fat diet induced hepatic insulin resistance is not related to changes in
      hypothalamic mRNA expression of NPY, AgRP, POMC and CART in mice.
AB  - The hypothalamic circuitry, apart from its impact on food intake, modulates
      insulin sensitivity to adapt metabolic conditions in the face of environmental
      fluctuations in nutrient availability. The purpose of the present study was to
      investigate the effects of 2 weeks high fat feeding in wildtype mice on (1)
      insulin sensitivity and triglyceride accumulation in liver and muscle in relation
      to (2) mRNA expression levels of Neuropeptide Y (NPY), Agouti-related protein
      (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated
      transcript (CART) in the hypothalamus. Two weeks of high fat feeding induced
      hepatic insulin resistance in the presence of increased hepatic triglyceride
      accumulation. In muscle, however, 2 weeks of high fat feeding did not result in
      changes in insulin sensitivity or in triglyceride content. mRNA expression levels
      of NPY, AgRP, POMC, and CART in the hypothalamus were not different between the
      groups. This study shows that 2 weeks of high fat feeding in mice does not affect
      mRNA expression levels of NPY, AgRP, POMC or CART, in the whole hypothalamus,
      despite induction of hepatic, but not peripheral, insulin resistance. Therefore,
      a major physiological role of these neuroendocrine factors in the induction of
      hepatic insulin resistance during a high fat diet seems less likely.

PMID- 15979207
TI  - Sensing the fat: fatty acid metabolism in the hypothalamus and the melanocortin
      system.
AB  - Recent evidence has demonstrated that circulating long chain fatty acids act as
      nutrient abundance signals in the hypothalamus. Moreover, pharmacological
      inhibition of fatty acid synthase (FAS) results in profound decrease in food
      intake and body weight in rodents. These anorectic actions are mediated by the
      modulation of hypothalamic neuropeptide systems, such as melanocortins. In this
      review, we summarize what is known about lipid sensing and fatty acid metabolism
      in the hypothalamus. Understanding these molecular mechanisms could provide new
      pharmacological targets for the treatment of obesity and appetite disorders, as
      well as novel concepts in the nutritional design.

PMID- 15979208
TI  - Rhythms of glycerophospholipid synthesis in retinal inner nuclear layer cells.
AB  - The present study demonstrates that the biosynthesis of phospholipids in the
      inner nuclear layer cells of the chicken retina displays daily rhythms under
      constant illumination conditions. The vertebrate retina contains circadian
      oscillators and photoreceptors (PRCs) that temporally regulate its own physiology
      and synchronize the whole organism to the daily environmental changes. We have
      previously reported that chicken photoreceptors and retinal ganglion cells (RGCs)
      present significant daily variations in their phospholipid biosynthesis under
      constant illumination conditions. Herein, we demonstrate that cell preparations
      highly enriched in inner nuclear layer cells also exhibit a circadian-regulated
      phospholipid labeling after the in vivo administration of [(32)P]phosphate or
      [(3)H]glycerol both in animals maintained under constant darkness or light for at
      least 48h. In constant darkness, there was a significant incorporation of both
      precursors into phospholipids with the highest levels of labeling around midday
      and dusk. In constant light, the labeling of (32)P-phospholipids was also
      significantly higher during the day and early night whereas the incorporation of
      [(3)H]glycerol into phospholipids, that indicates de novo biosynthesis, was
      greater during the day but probably reflecting a higher precursor availability at
      those phases. We also measured the in vitro activity of phosphatidate
      phosphohydrolase and diacylglycerol lipase in preparations obtained from the dark
      condition. The two enzymes exhibited the highest activity levels late in the day.
      When we assessed the in vitro incorporation of [(14)C]oleate into different
      lysophospholipids from samples collected at different phases in constant
      darkness, reaction catalyzed by lysophospholipid acyltransferases II, labeling
      showed a complex pattern of daily activity. Taken together, these results
      demonstrate that the biosynthesis of phospholipids in cells of the chicken
      retinal inner nuclear layer exhibits a daily rhythmicity under constant
      illumination conditions, which is controlled by a circadian clock.

PMID- 15979209
TI  - Differences in the in vivo dynamics of neurotransmitter release and serotonin
      uptake after acute para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine
      revealed by chronoamperometry.
AB  - Illicit use of p-methoxyamphetamine (PMA) is rapidly increasing. However, little
      is known about the acute effects of PMA on neurotransmission in vivo. High-speed
      chronoamperometry was used to monitor neurotransmitter release and clearance in
      anesthetized rats after local application of PMA or 3,4
      methylenedioxymethamphetamine (MDMA). In striatum, PMA caused less
      neurotransmitter release than MDMA. PMA-evoked release could be partially blocked
      by pre-treatment with a serotonin (5-HT) reuptake inhibitor, suggesting that
      evoked 5-HT release contributed to the electrochemical signal and was mediated by
      the 5-HT transporter (SERT). MDMA-evoked release was not blocked by a SERT
      inhibitor, suggesting that primarily DA was released. To study the effect of
      these amphetamines on clearance of 5-HT mediated specifically by the SERT,
      clearance of exogenously applied 5-HT was measured in the CA3 region of the
      hippocampus. In contrast to the striatum where 5-HT is cleared by both the SERT
      and the dopamine transporter (DAT), 5-HT is cleared primarily by the SERT in the
      CA3 region. This is also a region where neither PMA nor MDMA evoked release of
      neurotransmitter. The maximal inhibition of 5-HT clearance was greater after PMA
      than MDMA. These data demonstrate in vivo (1) brain region variability in the
      ability of PMA and MDMA to evoke release of neurotransmitter; (2) that clearance
      of 5-HT in the striatum is mediated by both the SERT and the DAT; (3) distinct
      differences in the amount and nature of neurotransmitter released in the striatum
      after local application of PMA and MDMA and (4) that PMA is a more efficacious
      inhibitor of 5-HT clearance in the hippocampus than MDMA. These fundamental
      differences may account for the more severe adverse reactions seen clinically
      after PMA, compared to MDMA.

PMID- 15979210
TI  - Premorbid effects of APOE on synaptic proteins in human temporal neocortex.
AB  - APOE affects the risk of Alzheimer's disease (AD) and course of several other
      neurologic diseases. Experimental studies suggest that APOE influences
      synaptogenesis. We measured the concentration of two presynaptic proteins,
      synaptophysin and syntaxin 1, and also postsynaptic density-95 (PSD95), in
      superior temporal cortex from 42 AD and 160 normal brains, and determined the
      APOE genotypes. The concentration of both presynaptic proteins was approximately
      two-thirds lower in AD than normal brains and that of PSD95 one-third lower. No
      effect of APOE on synaptic proteins was found in advanced AD. However, in normal
      brain, epsilon4 was associated with lower concentrations of all three synaptic
      proteins and epsilon2 with significantly elevated PSD95 (p=0.03). A combined
      measure of synaptic proteins showed a significant linear decrease from epsilon2
      through epsilon3 to varepsilon4 (p=0.01). APOE influences the concentration of
      synaptic proteins in normal superior temporal cortex and may thereby affect the
      response to injury, and the risk and outcome of a range of neurologic diseases.

PMID- 15979211
TI  - Isolation of neural precursor cells from Alzheimer's disease and aged control
      postmortem brain.
AB  - Recent studies demonstrate that isolated neural precursor cells are capable of
      generating neurons, astrocytes, and oligodendrocytes from neurogenic regions of
      adult brain. Because these studies use surgically resected or fresh postmortem
      specimens from young subjects, it is not clear whether neural precursor cells
      remain in the brain of normal aged subjects or subjects with Alzheimer's disease
      (AD). The purpose of this study was to determine if viable precursor cells remain
      in aged control and AD brain. AD subjects have significantly fewer viable
      precursor cells in the hippocampus compared with age-matched normal control
      subjects. Musashi-1 and Ki-67-positive precursor cells from AD self renew, but
      reach senescence earlier than cells isolated from normal aged control subjects.
      Precursor cells from AD and aged normal control specimens can differentiate into
      tubulin- and Tuj-1-positive neurons and GFAP-positive astrocytes. This study
      demonstrates that viable precursor cells remain in AD and aged normal control
      brain specimens and can be induced to differentiate. These results raise the
      possibility of stimulation of inherent precursor cells of aged individuals or AD
      patients to replace neurons lost in aging and/or neurodegeneration.

PMID- 15979212
TI  - Mitochondrial alterations of retinal pigment epithelium in age-related macular
      degeneration.
AB  - Mitochondrial dysfunctions have been implicated in the pathophysiology of several
      age-related diseases including age-related macular degeneration (AMD), a
      progressive neurodegenerative disease affecting primarily the retinal pigment
      epithelium (RPE). The aims of our electron microscopic and morphometric studies
      were to reveal qualitative and quantitative alterations of mitochondria in human
      RPE from AMD and from age- and sex-matched controls. With increasing age a
      significant decrease in number and area of mitochondria, as well as loss of
      cristae and matrix density were found in both AMD and control specimens. These
      decreases were significantly greater in AMD than in normal aging. Alterations of
      mitochondria were accompanied by proliferation of peroxisomes and lipofuscin
      granules in both AMD and control specimens, although the difference between
      groups was significant only for peroxisomes. Unexpectedly, morphometric data
      showed that the RPE alterations seen in AMD may also develop in normal aging, 10
      15 years after appearing in AMD patients. These findings suggest that (i) the
      severity of mitochondrial and peroxisomal alterations are different between AMD
      and normal aging, and (ii) the timing of damage to RPE may be critical for the
      development of AMD. We conclude that besides the well-documented age-related
      changes in mitochondrial DNA, alterations of mitochondrial membranes may also
      play a role in the pathogenesis of AMD. These membranes could be a new target for
      treatment of AMD and other age-related diseases.

PMID- 15979213
TI  - Quantitative proteomics analysis of differential protein expression and oxidative
      modification of specific proteins in the brains of old mice.
AB  - The brain is susceptible to oxidative stress, which is associated with age
      related brain dysfunction, because of its high content of peroxidizable
      unsaturated fatty acids, high oxygen consumption per unit weight, high content of
      key components for oxidative damage, and the relative scarcity of antioxidant
      defense systems. Protein oxidation, which results in functional disruption, is
      not random but appears to be associated with increased oxidation in specific
      proteins. By using a proteomics approach, we have compared the protein levels and
      specific protein carbonyl levels, an index of oxidative damage in the brains of
      old mice, to these parameters in the brains of young mice and have identified
      specific proteins that are altered as a function of aging. We show here that the
      expression levels of dihydropyrimidinase-like 2 (DRP2), alpha-enolase (ENO1),
      dynamin-1 (DNM1), and lactate dehydrogenase 2 (LDH2) were significantly increased
      in the brains of old versus young mice; the expression levels of three
      unidentified proteins were significantly decreased. The specific carbonyl levels
      of beta-actin (ACTB), glutamine synthase (GS), and neurofilament 66 (NF-66) as
      well as a novel protein were significantly increased, indicating protein
      oxidation, in the brains of old versus young mice. These results were validated
      by immunochemistry. In addition, enzyme activity assays demonstrated that
      oxidation was associated with decreased GS activity, while the activity of
      lactate dehydrogenase was unchanged in spite of an up-regulation of LDH2 levels.
      Several of the up-regulated and oxidized proteins in the brains of old mice
      identified in this report are known to be oxidized in neurodegenerative diseases
      as well, suggesting that these proteins may be particularly susceptible to
      processes associated with neurodegeneration. Our results establish an initial
      basis for understanding protein alterations that may lead to age-related cellular
      dysfunction in the brain.

PMID- 15979215
TI  - Weather-dependent change of cesium, strontium, barium and tellurium contamination
      deposited as aerosols on various cultures.
AB  - Various types of plants (wheat, bean, lettuce, radish and grass) were
      contaminated by dry deposition of radioactive aerosols ((137)Cs, (85)Sr, (133)Ba
      and (123 m)Te) in order to supplement the radio-ecological data necessary for
      operational post-accidental codes. A few days after deposition, rainfalls were
      applied to these cultures to evaluate the influence of some characteristics of
      the rain on the contamination of the culture over time. On the other hand, for
      wheat and bean, the influence of the humidity condition of the foliage at the
      contamination time was considered. For a given plant species at a given
      vegetative stage, the four radionuclides were intercepted in an identical way.
      The interception varied from 30% for bean (young sprout) to 80% for lettuce (near
      maturity). The global transfer factor values were dependent on both the
      radionuclides and the plant species; nevertheless, a higher value was obtained
      for cesium, regardless of the plant and the rainfall (from 0.006 m(2)kg(fresh)(
      1) for wheat-grains - contaminated at the shooting stage - or for bean-pods -
      contaminated at the pre-flowering stage - to 0.1m(2)kg(fresh)(-1) for a whole
      lettuce). The analysis of the results allowed us on the one hand, to extract
      parameter values of the foliar transfer directly usable in operational codes, in
      particular those relating to barium and tellurium, unknown until then, and on the
      other hand, to lay the foundations of a future, more mechanistic model, taking
      into account the foliar processes in a finer way.

PMID- 15979214
TI  - Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory
      neurons of aged mice.
AB  - Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene
      expression that correlate with reduced sensory perception. In this study we
      compared young and aged mice to identify proteins that might contribute to this
      loss of sensation. We first show using behavioral testing that thermal
      sensitivity in aged male and female mice is reduced. Expression of sodium channel
      (Nav1.8 and Nav1.9) and transient receptor potential vanilloid (TRPV) channels in
      DRG and peripheral nerves of young and old male mice was then examined.
      Immunoblotting and RT-PCR assays showed reduced Nav1.8 levels in aged mice. No
      change was measured in TRPV1 mRNA levels in DRG though TRPV1 protein appeared
      reduced in the DRG and peripheral nerves. The GFRalpha3 receptor, which binds the
      growth factor artemin and is expressed by TRPV1-positive neurons, was also
      decreased in the DRG of aged animals. These findings indicate that loss of
      thermal sensitivity in aging animals may result from a decreased level of TRPV1
      and Nav1.8 and decreased trophic support that inhibits efficient transport of
      channel proteins to peripheral afferents.

PMID- 15979217
TI  - Ectopic nail formation in the hand.
AB  - This paper reports an unusual case of ectopic nail formation, reviews the
      literature and proposes a simple classification of this anomaly.

PMID- 15979218
TI  - Effect of age on detecting a loss of balance in a seated whole-body balancing
      task.
AB  - BACKGROUND: Most falls are attributed to a loss of balance without a quantitative
      definition of the term. It has been proposed that a loss of balance is detectable
      as an unusually large (anomalous) value of the system control error. The
      hypotheses were tested that age will not affect the detection of control error
      anomaly, or prediction of the associated compensatory response, in a challenging
      balancing task. METHODS: Twenty healthy older adults were asked to sit and
      balance a chair over its rear legs for as long as possible. The dominant foot's
      ground reaction force and the chair's sagittal-plane acceleration represented the
      system input and output, respectively. Control error was the difference between
      actual and expected acceleration output from a self-identified forward internal
      model of the system. A control error anomaly was detected once the error crossed
      a threshold set at three standard deviations (3-Sigma) above the mean of baseline
      data. Results from five trials were compared to published results in 20 healthy
      young adults. FINDINGs. A control error anomaly was successfully detected in 91%
      of 91 older adult trials, statistically similar to the 92% success rate obtained
      previously in young adults. A response was predicted in 57% of the 77 older adult
      trials with responses, significantly less than the 92% obtained in the young
      adult trials (age effect significant: P<0.005). INTERPRETATION: The condition
      leading to uncontrolled backward acceleration of the chair was reliably detected
      in both groups. While the young waited to respond to this condition, older
      subjects responded prematurely.

PMID- 15979219
TI  - Cognitive-behavioral treatment for childhood sleep disorders.
AB  - Sleep problems are very prevalent during childhood and may have adverse
      developmental impact. The efficacy of a number of cognitive-behavioral
      interventions for the most prevalent problems such as difficulty falling asleep
      and night-wakings has been repeatedly demonstrated with relatively rapid outcomes
      and high success rates. Preventive interventions in infancy have shown some
      promise in lowering the rates of sleep problems in infants of trained parents.
      Cognitive-behavioral interventions have also been proposed for childhood
      parasomnias (sleepwalking, night terrors, nightmares, and rhythmic behaviors),
      however, very limited research has been conducted to assess the efficacy of these
      interventions. Specific methodological issues, limitations and needs have been
      identified in the clinical literatures. These issues include: (a) integrating
      objective sleep assessment methods in clinical research; (b) identifying the
      specific curative factors of various effective interventions; (c) the absence of
      long-term follow-up studies for assessing relapse problems; (d) assessing the
      role of mode of delivery (i.e., professional consultation versus written
      information) in treatment efficacy; and (e) the need to expand the research on
      clinical interventions for the parasomnias.

PMID- 15979220
TI  - Consistency of memory for emotionally arousing events: a review of prospective
      and experimental studies.
AB  - Although emotionally arousing events are more memorable than ordinary daily life
      events, the nature of memories for emotionally arousing events is widely debated.
      On the one hand, researchers consider memories for highly emotional events as
      malleable and subject to distortion, while on the other hand these memories are
      perceived as both indelible and consistent over the lifetime. Up till now, a
      systematic comparison of research findings on consistency of memory for emotional
      events is lacking. This paper is the first effort to summarize available studies
      on consistency of memory for emotionally arousing events and to address
      methodological limitations and suggestions for future research as well. In
      general, findings show that quality of the selected studies is sufficient to
      good, with studies with victims of assault and studies on war-exposure reaching
      higher quality scores than studies on flashbulb memories and experimental memory
      studies. Victims of assault or war-exposure tend to amplify their memories for
      the event, while results from flashbulb memory research and experimental research
      suggest that memory for emotional events is either stable or diminishes over
      time.

PMID- 15979222
TI  - The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and
      definition(s).
AB  - The no-observed-adverse-effect-level (NOAEL) is an important part of the non
      clinical risk assessment. It is a professional opinion based on the design of the
      study, indication of the drug, expected pharmacology, and spectrum of off-target
      effects. There is no consistent standard definition of NOAEL. This is based, in
      part, on the varied definitions of what constitutes an adverse effect.
      Toxicologists, either investigating or reviewing, have not been consistent in
      defining an effect as either adverse or acceptable. The common definition of
      NOAEL, "the highest experimental point that is without adverse effect," serves us
      well in general discussions. It does not, however, address the interpretation of
      risk based on toxicologically relevant effects, nor does it consider the
      progression of effect with respect to duration and/or dose. This paper will
      discuss the issues and application of a functional definition of the NOAEL in
      toxicology evaluations.

PMID- 15979221
TI  - Human pharmaceuticals in US surface waters: a human health risk assessment.
AB  - The detection of low levels of pharmaceuticals in rivers and streams, drinking
      water, and groundwater has raised questions as to whether these levels may affect
      human health. This report presents human health risk assessments for 26 active
      pharmaceutical ingredients (APIs) and/or their metabolites, representing 14
      different drug classes, for which environmental monitoring data are available for
      the United States. Acceptable daily intakes (ADIs) are derived using the
      considerable data that are available for APIs. The resulting ADIs are designed to
      protect potentially exposed populations, including sensitive sub-populations. The
      ADIs are then used to estimate predicted no effect concentrations (PNECs) for two
      sources of potential human exposure: drinking water and fish ingestion. The PNECs
      are compared to measured environmental concentrations (MECs) from the published
      literature and to maximum predicted environmental concentrations (PECs) generated
      using the PhATE model. The PhATE model predictions are made under conservative
      assumptions of low river flow and no depletion (i.e., no metabolism, no removal
      during wastewater or drinking water treatment, and no instream depletion). Ratios
      of MECs to PNECs are typically very low and consistent with PEC to PNEC ratios.
      For all 26 compounds, these low ratios indicate that no appreciable human health
      risk exists from the presence of trace concentrations of these APIs in surface
      water and drinking water.

PMID- 15979223
TI  - The usefulness of single nucleotide polymorphisms (SNPs) for genetic
      epidemiological investigation of complex psychiatric diseases.
AB  - The genetic epidemiology of complex psychiatric diseases has become a much
      studied and very prospering field. It is widely believed that many genetic
      factors contribute to the various phenotypes and diseases, with overall
      contributions of a single factor being comparatively minor. The study of choice
      in such settings is the investigation of allelic association, which may be
      performed in a variety of ways. Here single nucleotide polymorphisms are an
      indispensable tool.

PMID- 15979224
TI  - A comprehensive evaluation of the testicular toxicity of dichlorvos in Wistar
      rats.
AB  - Assessments of the reproductive toxicity of organophosphorus insecticides are
      important public health issues. This study aimed at defining the testicular
      toxicity of dichlorvos (DDVP) since this toxicity was suspected by our previous
      survey on pesticide sprayers and in some earlier publications during the 1970s.
      Ten-week-old Wistar rats were divided into four groups (n=8 or 9) and were
      injected subcutaneously with DDVP (0, 1, 2 or 4 mg/kg) 6 days a week for 9 weeks.
      After that period, erythrocyte cholinesterase (ChE) activities decreased dose
      dependently, showing 44-55% inhibition among the treated groups. No significant
      difference was observed in the reproductive organ weights in any treated groups
      compared with the control group. Sperm motility decreased slightly but
      significantly in the 1 and 4 mg/kg groups, and significant regressions were
      observed between sperm motility and both blood ChE activity and urinary
      concentration of dimethyl phosphate (DMP), a urine metabolite of DDVP. However,
      sperm counts and sperm morphology in the cauda epididymidis, plasma testosterone
      concentrations, and histopathology in the testes in all the treated groups were
      not significantly different from those of the control group. Since only the sperm
      motility deteriorated by DDVP exposure at doses inducing marked inhibition of
      cholinesterase activities in the rats, it was suggested that the risk of
      testicular dysfunction posed to occupationally exposed humans would be small in
      terms of the effect of DDVP exposure alone. This conclusion was also supported by
      an estimate of the decrease in human sperm motility based on the urinary DMP
      concentrations observed in actual occupational settings.

PMID- 15979226
TI  - Bond strength of a mild self-etch adhesive with and without prior acid-etching.
AB  - The self-etch approach provides dentists with a generation of user-friendly and
      less technique-sensitive adhesives. Nevertheless, some concern has been raised
      regarding their bonding effectiveness to enamel, in particular when so-called
      'mild' self-etch adhesives are employed. OBJECTIVES: The purpose of this study
      was to test the hypothesis that the two-step self-etch adhesive Clearfil SE Bond
      (C-SE; Kuraray, Osaka, Japan) bonds equally effective to enamel/dentin either
      with or without prior etching with phosphoric acid. METHODS: Bur-cut
      enamel/dentin surfaces prepared from human molars were partially split in two
      halves by cutting a shallow groove. One half was first etched with 40% phosphoric
      acid (K-etchant), while protecting the other half by holding a razor blade in the
      groove. Next, C-SE was applied strictly following the manufacturer's
      instructions, after which the surface was built up using Z100 (3M Espe). After 24
      h water storage, micro-specimens were prepared with the interface circularly
      constricted using a Micro-Specimen Former, prior to micro-tensile bond strength
      (MPa) measurement. In addition, interfaces of C-SE with enamel/dentin prepared
      with and without beforehand acid etching were examined by Feg-SEM and TEM.
      RESULTS: Beforehand etching significantly increased the bonding effectiveness of
      C-SE to enamel. A clearly more micro-retentive surface was revealed by TEM and
      Feg-SEM when enamel was etched. Phosphoric-acid etching prior to C-SE application
      on dentin significantly decreased the muTBS to dentin. TEM provided indications
      of a low-quality hybrid layer after beforehand phosphoric-acid etching.
      CONCLUSION: Using C-SE, additional etching with phosphoric acid to improve
      bonding effectiveness should be limited to enamel.

PMID- 15979225
TI  - Oral exposure to culture material extract containing fumonisins predisposes swine
      to the development of pneumonitis caused by Pasteurellamultocida.
AB  - Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticillioides and F.
      proliferatum that commonly occurs in maize. In swine, consumption of contaminated
      feed induces liver damage and pulmonary edema. Pasteurella multocida is a
      secondary pathogen, which can generate a respiratory disorder in predisposed
      pigs. In this study, we examined the effect of oral exposure to fumonisin
      containing culture material on lung inflammation caused by P. multocida. Piglets
      received by gavage a crude extract of fumonisin, 0.5mg FB(1)/kg body weight/day,
      for 7 days. One day later, the animals were instilled intratracheally with a non
      toxin producing type A strain of P. multocida and followed up for 13 additional
      days. Pig weight and cough frequency were measured throughout the experiment.
      Lung lesions, bronchoalveolar lavage fluid (BALF) cell composition and the
      expression of inflammatory cytokines were evaluated at the autopsy. Ingestion of
      fumonisin culture material or infection with P. multocida did not affect weight
      gain, induced no clinical sign or lung lesion, and only had minimal effect on
      BALF cell composition. Ingestion of mycotoxin extract increased the expression of
      IL-8, IL-18 and IFN-gamma mRNA compared with P. multocida infection that
      increased the expression of TNF-alpha. The combined treatment with fumonisin
      culture material and P. multocida delayed growth, induced cough, and increased
      BALF total cells, macrophages and lymphocytes. Lung lesions were significantly
      enhanced in these animals and consisted of subacute interstitial pneumonia. TNF
      alpha, IFN-gamma and IL-18 mRNA expression was also increased. Taken together,
      our data showed that fumonisin culture material is a predisposing factor to lung
      inflammation. These results may have implications for humans and animals
      consuming FB(1) contaminated food or feed.

PMID- 15979227
TI  - 13C NMR analysis of the etching efficacy of acidic monomers in self-etching
      primers.
AB  - It is well understood that the application of a self-etching primer enhances the
      bonding of the resin to the tooth. In this study, the demineralisation aspects by
      the Mega Bond Primer (MB) or the UniFil Bond Primer (UB) on the tooth were
      investigated by using liquid-state and solid-state 13C NMR techniques. The
      addition of hydroxyapatite or dentine to MB and the addition of dentine to UB
      resulted in the decrease in the peak intensity of the 13C NMR peaks attributed to
      the methacryloxy decyl phosphoric acid, MDP in the MB or 4-methacryloyloxy ethoxy
      carbonylphthalic acid, 4-MET in the UB. This decrease was because the MDP or 4
      MET demineralised the tooth and the calcium salts produced from the MDP or 4-MET
      were precipitated from the MB or UB solution. The NMR technique is very powerful
      in evaluating the demineralisation aspects of the tooth by a self-etching primer.
      However, the calcium salts produced by the MDP or 4-MET on the tooth surface
      would not facilitate retention in bonding, since these calcium salts were merely
      deposited on to the surface of the tooth.

PMID- 15979228
TI  - Single-bottle adhesives behave as permeable membranes after polymerisation. II.
      Differential permeability reduction with an oxalate desensitiser.
AB  - OBJECTIVES: This study examined the changes in hydraulic conductance and
      ultrastructure of dentine bonded with simplified etch-and-rinse adhesives to
      oxalate desensitiser pre-treated acid-etched dentine. METHODS: Human dentine
      disks were acid-etched, treated with an oxalate desensitiser (BisBlock, Bisco),
      and bonded with One-Step (OS), Single Bond (SB), OptiBond Solo Plus (OB) or Prime
      and Bond NT (PB). Similar disks from each group were acid-etched, and bonded
      without oxalate pre-treatment. Hydraulic conductance of the specimens was
      measured at 20 cm of water pressure and analysed with nonparametric statistical
      methods. Epoxy resin replicas of the smear layer-covered dentine and bonded
      dentine were examined with SEM for the extent of fluid transudation. Specimens
      bonded under perfusion were examined with TEM after tracer immersion. RESULTS: OB
      and PB exhibited a highly significant reversal of the reduced hydraulic
      conductance obtained with BisBlock on unbonded acid-etched dentine. Profuse water
      transudation across the bonded dentine was observed from the replicas. Adhesive
      interfaces were covered with spherical globules that interfered with dentine
      hybridization. Conversely, no significant difference in hydraulic conductance was
      observed in SB, between Bisblock pre-treated, unbonded and bonded acid-etched
      dentine. Significantly lower hydraulic conductance was shown on application of OS
      to Bisblock-treated acid-etched dentine. Water transudation was sparse,
      interfering surface globular structures were absent, and only angular subsurface
      crystals were seen in the dentinal tubules. CONCLUSIONS: Convective water fluxes
      through dentine may be reduced by applying Bisblock to acid-etched dentine before
      bonding with One-Step or Single Bond. However, reducing adhesive permeability
      with the use of oxalate desensitiser is not applicable to low acidity adhesives
      such as OptiBond Solo Plus and Prime and Bond NT.

PMID- 15979229
TI  - Two sequential phosphates 3' adjacent to the 8-oxoguanosine are crucial for
      lesion excision by E. coli Fpg protein and human 8-oxoguanine-DNA glycosylase.
AB  - Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) and human 8-oxoguanine
      DNA glycosylase (hOGG1) are base excision repair enzymes involved in the 8
      oxoguanine (oxoG) repair pathway. Specific contacts between these enzymes and DNA
      phosphate groups play a significant role in DNA-protein interactions. To reveal
      the phosphates crucial for lesion excision by Fpg and hOGG1, modified DNA
      duplexes containing pyrophosphate and OEt-substituted pyrophosphate
      internucleotide (SPI) groups near the oxoG were tested as substrate analogues for
      both proteins. We have shown that Fpg and hOGG1 recognize and specifically bind
      the DNA duplexes tested. We have found that both enzymes were not able to excise
      the oxoG residue from DNA containing modified phosphates immediately 3' to the 8
      oxoguanosine (oxodG) and one nucleotide 3' away from it. In contrast, they
      efficiently incised DNA duplexes bearing the same phosphate modifications 5' to
      the oxodG and two nucleotides 3' away from the lesion. The effect of these
      phosphate modifications on the substrate properties of oxoG-containing DNA
      duplexes is discussed. Non-cleavable oxoG-containing DNA duplexes bearing
      pyrophosphate or SPI groups immediately 3' to the oxodG or one nucleotide 3' away
      from it are specific inhibitors for both 8-oxoguanine-DNA glycosylases and can be
      used for structural studies of complexes comprising a wild-type enzymes bound to
      oxoG-containing DNA.

PMID- 15979230
TI  - Efficient adenoviral transduction of 3T3-F442A preadipocytes without affecting
      adipocyte differentiation.
AB  - The preadipocyte cell lines 3T3-L1 and 3T3-F442A are widely used to study the
      cellular mechanisms of preadipocyte differentiation and mature adipocyte
      functions. However, transfection with naked DNA is inefficient in these cell
      lines. Adenoviral gene transfer is a powerful technique to induce high levels of
      transgene expression. After failing to obtain 3T3-F442A stable transfectants, we
      studied different techniques designed to enhance the efficiency of adenoviral
      transduction in fat cells. First, we compared the effects of two agents known to
      significantly enhance adenoviral transgene transduction, namely the cationic
      lipid lipofectamine and the cationic polymer polylysine. We show here that
      lipofectamine-assisted adenoviral transduction was more efficient in 3T3-F442A
      than in 3T3-L1 preadipocytes at all tested multiplicity of infection.
      Lipofectamine, and more efficiently polylysine, yielded high and sustained levels
      of adenoviral transgene expression in 3T3-F442A preadipocytes. Adenoviral
      transgene expression was maintained throughout the differentiation process.
      Furthermore, the two agents also efficiently enhanced adenoviral transduction in
      mature 3T3-F442A adipocytes. Interestingly, neither protocol affected the
      differentiation process, morphological features or protein expression of mature
      adipocytes. These approaches could be of interest to study fat cell
      differentiation and the functions of mature adipocytes.

PMID- 15979231
TI  - Biochemical and functional characterization of ORF138, a mitochondrial protein
      responsible for Ogura cytoplasmic male sterility in Brassiceae.
AB  - In cytoplasmic male sterility (CMS), original mitochondrial genes contribute to
      sex determinism by provoking pollen abortion. The function of the encoded
      proteins remains unclear. We studied the ORF138 protein, responsible for the
      'Ogura' CMS, which is both used in hybrid seed production and present in natural
      populations. We analyzed the biochemical and structural properties of this
      protein in male-sterile plants and in E. coli. We showed that this protein
      spontaneously forms dimers in vitro. Truncated variants of the protein,
      containing either the hydrophobic or the hydrophilic moiety, also spontaneously
      dimerize. By fractionating mitochondria, we showed that ORF138 was strongly
      associated with the inner mitochondrial membrane of male-sterile plants. Our
      results also strongly suggest that ORF138 forms oligomers in male-sterile plant
      mitochondria. In E. coli, ORF138 was associated with the plasma membrane, as
      shown by membrane fractionation, and formed oligomers. The production of this
      protein strongly inhibited bacterial growth, but not by inhibiting respiration.
      The observed toxic effects required both the hydrophilic and hydrophobic moieties
      of the protein.

PMID- 15979232
TI  - The effect of acute aerobic exercise on stress related blood pressure responses:
      a systematic review and meta-analysis.
AB  - The beneficial impact of regular exercise on cardiovascular health is partly
      mediated by psychobiological mechanisms. However, the effect of acute exercise on
      psychobiological responses is unclear. Thus, we performed a systematic review of
      randomised controlled trials (RCTs) that examined the effect of acute aerobic
      exercise on blood pressure (BP) responses (the change from baseline to stress) to
      psychosocial laboratory tasks. Fifteen RCTs met inclusion criteria of which ten
      demonstrated significant reductions in post-exercise stress related BP responses
      compared with control (mean effect sizes for systolic and diastolic BP, 0.38 and
      0.40). Studies involving greater exercise doses tended to show larger effects,
      with the minimum dose to show a significant effect being 30 min at 50% VO2max. No
      other moderators emerged from the examination of participant characteristics,
      research designs and stressor characteristics. In conclusion, an acute bout of
      aerobic exercise appears to have a significant impact on the BP response to a
      psychosocial stressor.

PMID- 15979233
TI  - DNA databases.
AB  - This paper presents DNA algorithms for five relational algebra database
      operations, selection, projection, union, set difference, and Cartesian product
      on so-called DNA databases. A DNA database is a database where data records are
      encoded as DNA strands. The five operations mentioned before are fundamental in
      the field of databases and perform most of the data retrieval operations on
      current databases.

PMID- 15979234
TI  - Deoxy-adenosine-monophosphate (dAMP) di-n-butylester induces apoptosis by
      increasing the dATP level in HL-60 cells.
AB  - Deoxy-ATP is a potent inducer of apoptosis. We intended to synthesize a
      lipophilic dAMP derivative which, according to our working hypothesis penetrates
      into the cell, is converted to dAMP by intracellular esterases and to dATP by
      nucleotide kinases. We synthesized dAMP-di-n-butylester (DAB) and tested it. We
      found that it fulfills the above-described expectations. DAB treatment decreases
      the viability of HL-60 cells, increases the dATP concentration and induces
      apoptogenic cytochrome c release from mitochondria with concomitant elevation of
      caspase-9 activity. Our results indicate that use of dAMP derivatives with masked
      phosphate may be a feasible approach for pharmacological elevation of
      intracellular dATP and induction of apoptosis.

PMID- 15979235
TI  - Anti-proliferative activity of essential oil extracted from Thai medicinal plants
      on KB and P388 cell lines.
AB  - Anti-proliferative activity of essential oil from 17 Thai medicinal plants on
      human mouth epidermal carcinoma (KB) and murine leukemia (P388) cell lines using
      MTT assay were investigated. An amount of 1 x 10(4)cells/well of KB cell line and
      1 x 10(5) cells/well of P388 cell line were treated with the oil samples at
      different concentrations ranging from 0.019 to 4.962 mg/ml. In KB cell line,
      Guava (Psidium guajava L.) leaf oil showed the highest anti-proliferative
      activity with the IC(50) value of 0.0379 mg/ml (4.37 times more potent than
      vincristine) whereas Sweet Basil (Ocimum basilicum L.) oil gave the highest anti
      proliferative activity with the IC(50) value of 0.0362 mg/ml (12.7 times less
      potent than 5-FU) in P388 cell line. The results demonstrated the potential of
      essential oil from Thai medicinal plants for cancer treatment.

PMID- 15979236
TI  - PPAR-gamma ligands and amino acid deprivation promote apoptosis of melanoma,
      prostate, and breast cancer cells.
AB  - The PPAR-gamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) and ciglitazone,
      and the PPAR-alpha ligand, WY-14643, were examined for their effects on
      proliferation and apoptosis of A375 melanoma, DU145 and PC3 prostate cancer, and
      MB-MDA-231 breast cancer. While 15-deoxy-Delta(12,14)-prostaglandin J(2)
      inhibited proliferation of A375 melanoma, ciglitazone was inactive against this
      and the other cell lines. Restriction of specific amino acids known to inhibit
      proliferation and induce apoptosis sensitized all cell lines to ciglitazone, and
      the combined effects were greater than the individual effects of either
      treatment. WY-14643 alone or in combination with amino acid deprivation was
      inactive. Normal fibroblasts were resistant to the treatments.

PMID- 15979237
TI  - Effects of vegetation and fertilization on weathered particles of coal gob in
      Shanxi mining areas, China.
AB  - Combined application of sewage sludge and chemical fertilizer in weathered
      particles of coal gob (WPCG) was studied by pot-scale trials. The accumulation of
      available nutrients and weathering process of coal gob piles were also
      investigated by field trial. It was showed that combined application of sewage
      sludge and chemical fertilizer increased yields of tall fescue, improved WPCG
      fertility especially its biological fertility. After application of sewage
      sludge, the microbial biomass carbon, urease activity and total microorganism
      population were, respectively, increased by 0.3-2.4, 1.8-2.8 and 34-150 times.
      Heavy metals did not accumulate in tall fescue after application of sewage sludge
      in WPCG. Available nutrients were accumulated in topsoil eight years after
      reclamation in the field trial. Moreover, the effects of biological weathering
      exceeded that of natural weathering in coal gob piles. The percentage of coal gob
      particle diameter smaller than 3mm in the reclamation sites was increased by 85
      203%, but 30% in the un-reclaimed sites. While that of greater than 10 mm in the
      un-reclaimed sites was decreased by 19%, however, 62-74% in the reclamation
      sites. It was concluded that combined application of sewage sludge and chemical
      fertilizer could help quickly establishing a self-maintaining vegetation system
      in the primary process of reclamation.

PMID- 15979238
TI  - Factors affecting the biodegradation of PCP by Pseudomonas mendocina NSYSU.
AB  - A pentachlorophenol (PCP) degrading bacterium was isolated from PCP-contaminated
      soils and identified as Pseudomonas mendocina NSYSU (P. mendocina NSYSU). The
      main objectives of this study were to (1) clarify the factors affecting the
      ability and efficiency of PCP biodegradation by P. mendocina NSYSU, and (2)
      optimize the use of this bacterium in bioremediation of PCP. Microcosm
      experiments were conducted to fulfill the objectives. In batch cultures, P.
      mendocina NSYSU used PCP as its sole source of carbon and energy and was capable
      of completely degrading this compound. This was confirmed by the stoichiometric
      release of chloride ion. Moreover, P. mendocina NSYSU was able to mineralize a
      high concentration of PCP (150 mg/L). Results from the oxygen concentration
      experiment reveal that the growth of P. mendocina NSYSU was inhibited under low
      oxygen and anaerobic conditions. Results indicate that the optimal growth
      conditions for P. mendocina NSYSU include the following: slightly acidic
      (6<pH<7), aerobic, and relatively moderate ambient temperature (20 degrees
      C<temperature<30 degrees C) conditions. Addition of extra carbon sources (sodium
      acetate and glucose) could not enhance the PCP biodegradation. No PCP byproducts
      were detected after eight days of incubation in this study. This suggests that P.
      mendocina NSYSU is able to effectively biodegrade PCP and its biodegradation
      byproducts without the accumulation of inhibitory toxic compounds. Results from
      this study could be used to assist the optimization of its use in bioremediation
      of PCP.

PMID- 15979239
TI  - Early nuclear translocation of endonuclease G and subsequent DNA fragmentation
      after transient focal cerebral ischemia in mice.
AB  - We investigated whether the endonuclease G (endoG) translocated from mitochondria
      to nucleus after transient focal cerebral ischemia (tFCI), thereby contributed to
      subsequent DNA fragmentation. Adult male mice were subjected to 60min of focal
      cerebral ischemia by intraluminal suture blockade of the middle cerebral artery.
      Western blot analysis for endoG was performed at various time points of tFCI.
      Nuclear endoG was detected as early as 4h after tFCI in the ischemic brain, and
      correspondingly mitochondrial endoG showed a significant reduction at 4h after
      reperfusion (p<0.01). Immunohistochemistry of endoG confirmed that the nuclear
      translocation of endoG was detected as early as 4h after tFCI in the middle
      cerebral artery (MCA) territory of the ischemic brain. Double immunofluorescent
      staining with endoG and AIF showed that endoG was predominantly colocalized with
      AIF at 24h after tFCI. Double staining with endoG immunohistochemistry and TdT
      mediated dUTP-biotin nick end labeling showed a spatial relationship between
      endoG expression and DNA fragmentation at 24h after tFCI. These data suggest that
      the early nuclear translocation of endoG occurs and could induce DNA
      fragmentation in the ischemic brain after tFCI.

PMID- 15979240
TI  - Analysis of the strongylid nematodes (Nematoda: Strongylidae) community after
      deworming of brood horses in Ukraine.
AB  - Communities of intestinal helminths in horses are commonly studied post mortem.
      The study objectives were here to examine the species composition of the
      strongylid community in brood horses in Ukraine after deworming with an
      aversectin drug Univerm. The site distribution of the strongylid species was
      analysed according to dynamics of their expulsion in faeces. Forty-four horses of
      different ages from Poltavska oblast (22 horses), Kyivska oblast (17 horses) and
      Sumska oblast (5 horses) of Ukraine were included in the study. Horses were
      treated with Univerm anthelmintic (0.2% aversectin) at a dose rate of 0.5mg
      aversectin preparation per kg body weight. Faecal sampling (200 g each) was
      performed at 24, 36, 48 and 60 h post treatment, and all nematodes expelled were
      collected and identified. The largest numbers of strongylids were expelled at 24-
      36 h after treatment. Twenty-five nematode species from the subfamilies
      Strongylinae and Cyathostominae were identified. The number of strongylid species
      found per horse ranged from 7 to 20, on an average 11+/-3.6 (S.D.). The number of
      cyathostomin species found per horse ranged from 7 to 16, on an average 10+/-2.3
      (S.D.). Cylicocyclus nassatus and Cyathostomum catinatum were the most dominant
      species were found in 100% of horses, amounting to 36.3% and 17.6% of the total
      number of strongylids collected, respectively. C. longibursatus, C. ashworthi,
      Cylicostephanus calicatus, C. leptostomus and C. minutus were identified in more
      than 80% horses and represented 39.9% of the total number of strongylids
      collected. The dynamics of the different strongylid species expelled was
      irregular. Correlation between the time of cyathostomin species expulsion in
      faeces and their predicted localisation inside the horse intestine was found.
      Species mainly localised in the caecum were found in faeces later than those
      species localised in the dorsal and ventral colons. Larvae and adult Parascaris
      equorum, Oxyuris equi and botfly larvae from the genus Gasterophilus were also
      found in horse faeces. This investigation shows that is possible to study the
      horse strongylid community after deworming with aid of an aversectin drug. The
      results obtained here correspond to those recorded in previous autopsy surveys in
      other countries.

PMID- 15979241
TI  - Spectral integration in primary auditory cortex: laminar processing of afferent
      input, in vivo and in vitro.
AB  - Auditory cortex neurons integrate information over a broad range of sound
      frequencies, yet it is not known how such integration is accomplished at the
      cellular or systems levels. Whereas information about frequencies near a neuron's
      characteristic frequency is likely to be relayed to the neuron by lemniscal
      thalamocortical inputs from the ventral division of the medial geniculate
      nucleus, we recently proposed that information about frequencies spectrally
      distant from characteristic frequency is mainly relayed to the neuron via
      "horizontal" intracortical projections from neurons with spectrally-distant
      characteristic frequencies [J Neurophysiol 91 (2004) 2551]. Here we test this
      hypothesis by using current source density analysis to determine if
      characteristic frequency and spectrally-distant non-characteristic frequency
      stimuli preferentially activate thalamocortical and horizontal pathways,
      respectively, in rat auditory cortex. Characteristic frequency stimuli produced
      current source density profiles with prominent initial current sinks in layers 3
      and 4--the termination zone of lemniscal inputs from medial geniculate nucleus.
      In contrast, stimuli three octaves below characteristic frequency produced
      initial current sinks mainly in the infragranular layers. Differences between
      current source density profiles were only apparent for initial current sinks;
      profiles for longer-latency current sinks evoked by characteristic frequency and
      non-characteristic frequency stimuli overlapped to a greater degree, likely due
      to shared mechanisms of intracortical processing or to longer-latency
      thalamocortical contributions (lemniscal and nonlemniscal). To identify current
      source density profiles produced by activation of lemniscal thalamocortical
      inputs alone, we utilized the mouse auditory thalamocortical slice preparation.
      Electrical stimulation of the medial geniculate nucleus in vitro produced major
      current sinks in cortical layers 3/4, and excitation spread horizontally from
      this point throughout primary auditory cortex to produce current sinks in
      multiple cortical layers. These data support the hypothesis that relay of
      thalamocortical information throughout auditory cortex via horizontal
      intracortical projections may be the basis of broad spectral integration in vivo.

PMID- 15979243
TI  - Influence of photoperiod and sex on locomotor behavior of meadow voles (Microtus
      pennsylvanicus) in an automated light-dark 'anxiety' test.
AB  - This study examined the influence of photoperiod on affective behavior (anxiety)
      of adult male and female meadow voles (Microtus pennsylvanicus), maintained in
      either a long or short day photoperiod, when tested in an automated (VersaMax)
      light-dark test. The light-dark test is based on an innate aversion of rodents to
      novel, brightly illuminated spaces and has been used with laboratory raised
      species, such as mice, to assess anxiety and/or fear related behaviors. Male and
      female meadow voles, housed either in a long day (LD: 16 h light) or short day
      (SD: 8 h light) photoperiod, were tested in the light-dark apparatus for 30 min
      on 3 consecutive days. All animals spent significantly (p < 0.001) less time in
      the brightly lit chamber (900 lux) than in the dark chamber. LD voles, especially
      females, spent significantly less time in the brightly lit area than did SD
      voles. Both horizontal and vertical movements occurred less frequently per unit
      time in the dark area relative to the light, but only in the LD voles. LD female
      voles were the least active group in the dark area on the first test day but the
      most active group in the light area, despite spending the least amount of time in
      this area on the second and third test days. The present results show that LD
      voles exhibit more anxiety related behaviors in this test situation than do SD
      voles. LD females avoided the brightly lit area the most, particularly when the
      apparatus was novel. Thus, both photoperiod and sex influence situation-based
      anxiety in this species. These findings suggest that meadow voles are an
      excellent animal model in which to examine the role of gonadal hormones, and
      their modulation of defence related neural systems, in the induction of anxiety.

PMID- 15979242
TI  - Delayed inhibition of Nogo-A does not alter injury-induced axonal sprouting but
      enhances recovery of cognitive function following experimental traumatic brain
      injury in rats.
AB  - Traumatic brain injury causes long-term neurological motor and cognitive
      deficits, often with limited recovery. The inability of CNS axons to regenerate
      following traumatic brain injury may be due, in part, to inhibitory molecules
      associated with myelin. One of these myelin-associated proteins, Nogo-A, inhibits
      neurite outgrowth in vitro, and inhibition of Nogo-A in vivo enhances axonal
      outgrowth and sprouting and improves outcome following experimental CNS insults.
      However, the involvement of Nogo-A in the neurobehavioral deficits observed in
      experimental traumatic brain injury remains unknown and was evaluated in the
      present study using the 11C7 monoclonal antibody against Nogo-A. Anesthetized,
      male Sprague-Dawley rats were subjected to either lateral fluid percussion brain
      injury of moderate severity (2.5-2.6 atm) or sham injury. Beginning 24 h post
      injury, monoclonal antibody 11C7 (n=17 injured, n=6 shams included) or control Ab
      (IgG) (n=16 injured, n=5 shams included) was infused at a rate of 5 microl/h over
      14 days into the ipsilateral ventricle using osmotic minipumps connected to an
      implanted cannula. Rats were assessed up to 4 weeks post-injury using tests for
      neurological motor function (composite neuroscore, and sensorimotor test of
      adhesive paper removal) and, at 4 weeks, cognition was assessed using the Morris
      water maze. Hippocampal CA3 pyramidal neuron damage and corticospinal tract
      sprouting, using an anterograde tracer (biotinylated dextran amine), were also
      evaluated. Brain injury significantly increased sprouting from the uninjured
      corticospinal tract but treatment with monoclonal antibody 11C7 did not further
      increase the extent of sprouting nor did it alter the extent of CA3 cell damage.
      Animals treated with 11C7 showed no improvement in neurologic motor deficits but
      did show significantly improved cognitive function at 4 weeks post-injury when
      compared with brain-injured, IgG-treated animals. To our knowledge, the present
      findings are the first to suggest that (1) traumatic brain injury induces axonal
      sprouting in the corticospinal tract and this sprouting may be independent of
      myelin-associated inhibitory factors and (2) that post-traumatic inhibition of
      Nogo-A may promote cognitive recovery unrelated to sprouting in the corticospinal
      tract or neuroprotective effects on hippocampal cell loss following experimental
      traumatic brain injury.

PMID- 15979244
TI  - Pretreatment and during treatment risk factors for dropout among patients with
      substance use disorders.
AB  - OBJECTIVE: The aim of this study was to use pretreatment and treatment factors to
      predict dropout from residential substance use disorder program and to examine
      how the treatment environment modifies the risk for dropout. METHOD: This study
      assessed 3649 male patients at entry to residential substance use disorder
      treatment and obtained information about their perceptions of the treatment
      environment. RESULTS: Baseline factors that predicted dropout included younger
      age, greater cognitive dysfunction, more drug use, and lower severity of alcohol
      dependence. Patients in treatment environments appraised as low in support or
      high in control also were more likely to drop out. Further, patients at high risk
      of dropout were especially likely to dropout when treated in a highly controlling
      treatment environment. CONCLUSION: Better screening of risk factors for dropout
      and efforts to create a less controlling treatment environment may result in
      increased retention in substance use disorder treatment.

PMID- 15979245
TI  - National Youth Anti-Drug Media Campaign and school-based drug prevention:
      Evidence for a synergistic effect in ALERT Plus.
AB  - This analysis examined the possible synergistic effect of exposure to the
      National Youth Anti-Drug Media Campaign and a classroom-based drug prevention
      curriculum among 9th grade students participating in a randomized trial of ALERT
      Plus. A total of 45 South Dakota high schools and their middle-school feeder(s)
      were randomly assigned to an ALERT condition (basic prevention curriculum
      delivered in 7th and 8th grades), an ALERT Plus condition (basic curriculum with
      booster lessons added for 9th and 10th grades), or a control condition. Marijuana
      use in the past month was significantly less likely among ALERT Plus students
      reporting at least weekly exposure to anti-drug media messages. The National
      Youth Anti-Drug Media Campaign may have led to reductions in marijuana use among
      youth who simultaneously received school-based drug prevention.

PMID- 15979246
TI  - Factors associated with lifetime history of drug treatment among substance
      dependent women.
AB  - There is extensive research on factors related to substance use treatment
      retention and completion but less is known about factors related to treatment
      initiation, particularly for women. This paper examines factors associated with a
      lifetime history of substance abuse treatment among women with drug abuse or
      dependence. Baseline interview data, using the Addiction Severity Index (ASI)
      that obtained during a randomized clinical trial was analyzed comparing women
      with no history of drug treatment with women with a history at least one drug
      treatment episode. Of the 153 women, 47.4% had a lifetime history of drug
      treatment compared to 52.6% who have never enrolled in drug treatment. After
      multiple logistic regression, craving drugs at least 15 days in the past month,
      using cocaine at least 15 days in the past month, ASI alcohol composite score,
      perceived seriousness of legal problems, history of at least 3 pregnancies, and
      history of physical abuse by a known person, were independently associated with
      drug treatment.

PMID- 15979247
TI  - College student drinking: perception of the norm and behavioral intentions.
AB  - Social norm campaigns assume that college students desire to increase their
      drinking, and may eventually do so, to match inflated perceptions of peer
      drinking. We assessed 171 college students on self-reported drinking, desired
      drinking and perception of peer drinking at baseline, and assessed 139 of those
      students one month later. Participants who believed their peers drank more than
      they were hypothesized to desire to increase their alcohol consumption to match
      the perceived norm. This hypothesis was not supported; however, 91% of
      participants believed their peers drank more than themselves. It was also
      hypothesized that participants who wished to drink more would drink more in the
      future. Participants who desired to increase their drinking did not report a
      significant change in drinking behavior one month later, but participants who
      initially desired to maintain or decrease their drinking reported significant
      decreases across the following month. College student overestimation of peer
      drinking and the college environment are discussed. Social norm campaigns should
      consider behavioral intentions, and the underlying assumptions of these campaigns
      should be further tested.

PMID- 15979248
TI  - Psychometric characteristics of a Spanish version of the DAST-10 and the RAGS.
AB  - Although Hispanics/Latinos constitute the largest ethnic minority group in the
      United States, there are few culturally and linguistically valid Spanish language
      clinical assessment instruments. This shortage is even more critical in the
      addictions field. This article presents the psychometric characteristics of two
      drug abuse screening instruments; the Drug Abuse Screening Test (DAST-10), and
      the Reduce Annoyed Guilty Start (RAGS) test that were translated into Spanish.
      Participants included 60 drug abusers, 35 alcohol abusers, and 127 individuals
      with no alcohol and/or drug problem. Results indicated that the Spanish versions
      of the two drug abuse screening instruments were reliable and unidimensional and
      differentiated drug abusers from non-substance abusers and from alcohol abusers.

PMID- 15979249
TI  - Constituents of Agave americana and Agave barbadensis.
AB  - An investigation of Agave americana and Agave barbadensis resulted in the
      isolation of a new homoisoflavanoid, 7-hydroxy-3-(4-methoxybenzyl)-chroman (3),
      together with known compounds 7-hydroxy-3-(4-methoxybenzyl)-chroman-4-one (1),
      5,7-dihydroxy-3-(4-methoxybenzyl)-chroman-4-one (2), cantalasaponin-1 (4), and 2
      hydroxy-butanedioic acid-1-methyl ester (5).

PMID- 15979250
TI  - Hepatic and extrahepatic expression of vitellogenin genes in the zebrafish, Danio
      rerio.
AB  - Vitellogenins (Vtgs) are yolk precursor proteins in oviparous species and are
      cleaved into three portions-lipovitellin I (LVI), phosvitin (PV), and
      lipovitellin II (LVII)-in oocytes in vertebrates. In the present study, we found
      that the zebrafish genome contains at least seven vtg genes (vtg1-7) encoding
      heterogeneous vitellogenins with three distinct types of Vtgs: type I (Vtg1, 4-7)
      contains all the three major portions but lacks the C-terminal half of LVII; type
      II (Vtg2) is the only one including intact three portions; type III (Vtg3) lacks
      both PV and the LVII C-terminal half. The seven vtgs were located in two
      different chromosomes: one (vtg3) in LG11 and the rest closely linked in LG22,
      probably arisen from local gene duplication events. All of the seven vtgs are
      predominantly expressed in female liver and can be induced in male liver by
      17beta-estradiol (E2). The level of vtg1 mRNA was about 100x and 1000x higher
      than those of vtg2 and vtg3 mRNAs. We also found vtg mRNAs in several non-liver
      tissues, but the expression level is generally <10% of that in the liver. In situ
      hybridization experiments confirmed that the extrahepatic expression was actually
      in adipocytes associated with several organs such as the intestine, ovary, and E2
      induced testis.

PMID- 15979252
TI  - Chloroplast membrane transport: interplay of prokaryotic and eukaryotic traits.
AB  - Chloroplasts are specific plant organelles of prokaryotic origin. They are
      separated from the surrounding cell by a double membrane, which represents an
      effective barrier for the transport of metabolites and proteins. Specific
      transporters in the inner envelope membrane have been described, which facilitate
      the exchange of metabolites. In contrast, the outer envelope has been viewed for
      a long time as a molecular sieve that offers a mere size constriction to the
      passage of molecules. This view has been challenged lately, and a number of
      specific and regulated pore proteins of the outer envelope (OEPs) have been
      identified. These pores seem to have originated by adaptation of outer membrane
      proteins of the cyanobacterial ancestor of the chloroplast. In a similar fashion,
      the transport of proteins across the two envelope membranes is achieved by two
      hetero-oligomeric protein complexes called Toc (translocon in the outer envelope
      of chloroplasts) and Tic (translocon in the inner envelope of chloroplasts). The
      phylogenetic provenance of the translocon components is less clear, but at least
      the channel protein of the Toc translocon is of cyanobacterial origin.
      Characteristic of cyanobacteria and chloroplasts is furthermore a specialized
      internal membrane system, the thylakoids, on which the components of the
      photosynthetic machinery are located. Despite the importance of this membrane,
      very little is known about its phylogenetic origin or the manner of its
      synthesis. Vipp1 appears to be a ubiquitous component of thylakoid formation,
      while in chloroplasts of land plants, additionally a vesicle transport system of
      eukaryotic origin might be involved in this process.

PMID- 15979251
TI  - Mitochondrial signal peptidases of yeast: the rhomboid peptidase Pcp1 and its
      substrate cytochrome C peroxidase.
AB  - The rhomboid peptidase Pcp1 of yeast is the first mitochondrial enzyme of this
      new class of serine peptidases. Pcp1 is an integral part of the inner membrane
      and was identified by its signal peptidase activity responsible for processing of
      the intermediate of cytochrome c peroxidase (iCcp1) to the mature enzyme. Here we
      describe studies on the expression of the PCP1 gene. Proteolytic processing of
      Pcp1 itself was found. The precursor and the intermediate of Ccp1 were localized
      to the inner membrane. The results confirm our previous report on a two-step
      processing pathway of cytochrome c peroxidase and the identification of the
      signal peptidases involved.

PMID- 15979253
TI  - Mitochondrial movement and inheritance in budding yeast.
AB  - Mitochondria are essential organelles that perform fundamental cellular functions
      including aerobic energy mobilization, fatty acid oxidation, amino acid
      metabolism, heme biosynthesis and apoptosis. Mitochondria cannot be synthesized
      de novo. Therefore, the inheritance of this organelle is an essential part of the
      cell cycle; that is, daughter cells that do not inherit mitochondria will not
      survive. The budding yeast, Saccharomyces cerevisiae, is a facultative aerobe
      that can tolerate mitochondrial mutations that would be lethal in other
      organisms. Therefore, yeast has been used extensively to study inheritance and
      segregation of mitochondria. As a result, much of what we know regarding
      mitochondrial inheritance has been uncovered using yeast as a model system. Here,
      we describe the latest developments in mitochondrial motility and inheritance.

PMID- 15979254
TI  - Why are many mRNAs translated to the vicinity of mitochondria: a role in protein
      complex assembly?
AB  - The longstanding question of the presence of mitochondria-bound polysomes has
      been recently revisited using new approaches. Genome-wide analyses provided
      evidence that many genes are actually translated on mitochondria-bound polysomes
      and GFP-labeling techniques have shown that, in vivo, the 3'UTR sequence of these
      genes contains signals which can target hybrid RNA molecules to the proximity of
      mitochondria. Evolutionary conservation of some of these signals will be
      presented. Interestingly, class I mRNA which are translated on free polysomes and
      class II mRNA which are translated on mitochondria-bound polysomes have, mostly,
      eukaryotic and prokaryotic origins respectively. Using ATP2, a typical
      prokaryotic-derived gene, as a model for class II mRNA, we showed that its 3'UTR
      sequence is essential both for a correct addressing of mRNA to mitochondria
      proximity and to a proper production of functional ATP synthases. These different
      observations suggest that prokaryotic-derived genes are, like the contemporary
      mitochondrial genes, translated near mitochondrial membranes. In both cases this
      locus specific translation process might be connected to a correct complex
      assembly program and the cases of ATP synthase and cytochrome c oxidase complexes
      will be considered in this respect.

PMID- 15979255
TI  - Spef1, a conserved novel testis protein found in mouse sperm flagella.
AB  - We describe the cloning and characterisation of Spef1, a novel testis-specific
      gene. Spef1 has evolutionary orthologues in a wide range of species including
      mammals, other vertebrates, Drosophila, and protozoans with motile cilia or
      flagella. A second homologue of the gene, Spef2, is also present in several
      species, suggesting that these genes form part of a novel gene family. The Spef1
      protein has two conserved domains, one of which is more strongly conserved in
      both homologues of the gene. Expression analysis of Spef1 in mice shows that it
      is expressed predominantly in adult testis, suggesting a role in spermatogenesis.
      Using an antibody generated to recombinant Spef1, we demonstrate a specific
      pattern of Spef1 localisation in the seminiferous epithelium of adult mouse
      testis. Further immunohistochemical analysis using electron microscopy shows
      Spef1 to be present in the tails of developing and epididymal sperm, internal to
      the fibrous sheath and around the outer dense fibres of the sperm flagellum.

PMID- 15979256
TI  - Basal colon crypt cells are more sensitive than surface cells toward hydrogen
      peroxide, a factor of oxidative stress.
AB  - Products of oxidative stress are possibly important risk factors for colon
      cancer. It is necessary to assess their toxicity in tumour target cells, which
      include the stem cells and dividing daughter cells located in the bottom of the
      colon crypts. Here, we investigated the sensitivity of crypt cells towards
      hydrogen peroxide (H(2)O(2)), a key genotoxin associated with oxidative stress.
      Primary rat colonocytes, were isolated from different regions of the crypts by
      fractionated digestion. Differentiation was determined by measuring the alkaline
      phosphatase activity. Deoxyribonucleic acid (DNA) damage and oxidised DNA bases
      were determined using the modified version Comet assay with endonuclease III.
      Major findings were that rat colonocytes had high levels of endogenous DNA single
      strand breaks, with no significant difference from basal crypt cells to surface
      cells. However, cells of the basal crypt had more oxidised DNA pyrimidines, which
      were probably a reflection of preceding in vivo exposure. An in vitro treatment
      with H(2)O(2) significantly increased DNA strand breaks in all fractions of rat
      colonocytes, but again cells of the basal crypt were more sensitive than cells of
      the surface epithelium. We conclude that cells from lower crypt sections are more
      sensitive towards H(2)O(2) than differentiated cells at the surface of the crypt.

PMID- 15979257
TI  - Vinclozolin, a widely used fungizide, enhanced BaP-induced micronucleus formation
      in human derived hepatoma cells by increasing CYP1A1 expression.
AB  - Vinclozolin, a widely used fungicide, can be identified as a residue in numerous
      vegetable and fruit samples. To get insight in its genetic toxicity, we
      investigated the genotoxic effect of vinclozolin in the human derived hepatoma
      cell line HepG2 using the micronucleus (MN) assay. Additionally, to evaluate the
      co- or anti-mutagenic potency of vinclozolin, we treated HepG2 cells with
      different concentrations of vinclozolin for 24 h. Subsequently, the cells were
      exposed to benzo[a]pyrene (BaP) for 1h. Exposure of HepG2 cells to 50-400 microM
      vinclozolin alone did not cause any induction of micronuclei. However, a
      pronounced co-mutagenic effect was observed. MN frequencies caused by BaP
      increased by 30.6%, 52.8% and 65.3% after pretreatment of the cell cultures with
      50, 100 and 200 microM vinclozolin, respectively. The highest concentration (400
      microM) of vinclozolin tested caused cytotoxicity. Therefore, micronuclei were
      not considered for that concentration. To clarify the mechanism of
      cogenotoxicity, we assayed cytochrome P450 1A1 (CYP1A1), which plays a pivotal
      role in activation of BaP. Cells exposed to vinclozolin led to significant
      increase of CYP1A1 expression in Western blot. The result suggested that
      induction of CYP1A1 by vinclozolin account for its enhancing effect on
      genotoxicity caused by BaP.

PMID- 15979258
TI  - Protective effect of plant extract from Onobrychis ebenoides on ovariectomy
      induced bone loss in rats.
AB  - OBJECTIVE: Certain plant extracts have been the object of recent studies due to
      their mild estrogenic action and their possible potential role in osteoporosis
      prevention and/or treatment. The present study was undertaken to investigate the
      possible protective effect of the aqueous solution of the plant Onobrychis
      ebenoides, with proven in vitro mild estrogenic action, on bone mass loss of the
      ovariectomized (Ovx) rat experimental model of osteoporosis. METHODS: Forty
      intact female mature (10-month-old) Wistar rats were separated into three groups:
      Ovx, Ovx plus plant extract (Ph) and sham-operated (control). Ph administration
      in the drinking water at a dose of 300 mg/kg body weight/day commenced
      immediately after Ovx. Bone mineral density (BMD) values, percentage change from
      the baseline measurement and histomorphometry of the tibia, as well as body and
      uterine weight, were examined and compared between groups. RESULTS: Comparison of
      BMD absolute values of the whole tibia of Ovx + Ph and Ovx animals at both 3 and
      6 months post-Ovx were highly significant (p < 0.0005), showing a protective
      effect on treated animals. The extract did not appear to have such a beneficial
      effect on BMD of the proximal tibia of the treated animals compared to the Ovx
      animals after 3 months; however, a significant protective effect was observed at
      6 months post-Ovx in treated animals compared to the Ovx (p = 0.015). When the %
      changes from baseline measurement of the whole tibia of Ovx + Ph and controls
      were compared, there was no significant difference at 3 or 6 months,
      demonstrating a highly protective effect; the respective comparisons of proximal
      tibia % changes did not display such protection. Body and uterine weight
      comparisons showed no significant difference between Ovx and treated rats,
      whereas, the level of significance for each group compared to controls was p <
      0.0005. CONCLUSIONS: The Ph studied showed a highly significant protective effect
      on BMD of the whole tibia of Ovx rats after 3 and 6 months of treatment, compared
      to the non-treated animals. Its effect on the proximal tibia was less pronounced,
      but also statistically significant compared to non-treated rats after 6 months.
      The lack of significant effect on body and uterine weight is in favor of its
      selective estrogen receptor modulator-like activity, and merits further studies.

PMID- 15979259
TI  - In vitro percutaneous absorption studies and in vivo evaluation of anti
      inflammatory activity of essential fatty acids (EFA) from fish oil extracts.
AB  - The aim of the present study was to evaluate the in vitro percutaneous absorption
      and the in vivo anti-inflammatory activity of EPA and DHA fatty acids from three
      oily extracts, obtained by acetonic extractions from the entrails of different
      varieties of Mediterranean fishes such as mackerel (Scomber scombrus), sardine
      (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus). In the first
      part of our research, we focused our attention on the characterization of the
      oily extracts to determine their omega-3 polyunsaturated fatty acid content,
      then, we evaluated the in vitro percutaneous absorption through excised human
      skin (stratum corneum/epidermis membranes; SCE) of EPA and DHA contained in the
      extracts. In the second part, the fish oil which guaranteed the best in vitro
      permeation profile of these omega-3 fatty acids was studied in order to evaluate
      its inhibiting ability towards the in vivo UVB-induced skin erythema. From the
      results obtained, all the fish oils tested in this study presented significant
      amounts of omega-3 fatty acids EPA and DHA, and particularly sardine oil extract
      showed higher concentrations of these substances compared to the other two fish
      oils. The in vitro experiments revealed interesting fluxes of these compounds
      from sardine extract through the stratum corneum/epidermis membranes and an
      appreciable anti-inflammatory activity against UVB-induced erythema in human
      volunteers was also observed.

PMID- 15979260
TI  - Enzymatic characterization of lipid-based drug delivery systems.
AB  - The present work introduces a simple and robust in vitro method for enzymatic
      characterisation of surface properties of lipid dispersions in aqueous media. The
      initial lipolysis rate in biorelevant media, using pancreatic lipase and a self
      microemulsifying formulation (SMEDDS) containing digestible lipids as substrate,
      was determined. The impact of incorporating two sparingly water soluble model
      drugs, probucol and halofantrine, into the SMEDDS was studied. It was found that
      both model drugs reduced the initial rate of lipolysis compared with the vehicle,
      probucol having a larger effect than halofantrine. The reduction of initial
      lipolysis rate indicates that probucol and halofantrine are bound in the
      water/emulsion interface limiting the substrate availability.

PMID- 15979261
TI  - Self-association properties of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2
      [tetrazole-5-yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS
      088), an antiglaucoma ophthalmic agent.
AB  - Self-association properties of CS-088, an antiglaucoma ophthalmic agent, were
      investigated. Various analytical methods, such as surface tension measurement,
      demonstrated that CS-088 is a self-associating compound with critical micellar
      concentration (CMC) of approximately 10 mg/mL. Light scattering analysis revealed
      that the micellar molecular weight (MMW) of CS-088 aggregates well above the CMC
      was approximately 2260, corresponding to a pentamer. In addition, the MMW
      corresponding to a dimer was detected by NMR spectroscopy, indicating that self
      association of monomers to pentamers is via the formation of dimers. According to
      the Stokes-Einstein equation, hydrodynamic radii of the dimer and pentamer were
      calculated to be 0.87 and 1.16 nm, respectively. The concentration-dependent
      change in the NMR chemical shift indicated that hydrophobic interaction between
      biphenyl groups is an important factor in the self-association of CS-088
      molecules. Furthermore, measurement of particle size distribution using a Nicomp
      Submicron Particle-Sizer revealed that the addition of either n-propanol or urea
      to CS-088 solution led to monomerization of the dimers and pentamers, suggesting
      that not only hydrophobic interaction but also hydrogen bonding is involved in
      stabilizing CS-088 aggregates. No bigger aggregate than a pentamer was formed in
      the absence of NaCl, whereas further aggregation was observed with increasing
      concentrations of NaCl.

PMID- 15979262
TI  - Application of on-line Raman spectroscopy for characterizing relationships
      between drug hydration state and tablet physical stability.
AB  - Experiments were conducted to elucidate the relationship between risedronate
      sodium (RS) hydration state and the physical stability of tablets containing RS.
      The RS crystal lattice contains channels occupied by water, which is removed by
      drying processes at temperatures below the boiling point of water, causing a
      reversible contraction of the crystal lattice. In this study, risedronate sodium
      was wet granulated followed by fluid bed drying to final granulation moisture
      contents between 1 and 7%, and then compressed into tablets. During drying, the
      RS solid-state form was continuously monitored using on-line Raman spectroscopy.
      Raman spectra acquired in these experiments enabled direct monitoring of changes
      in the RS crystal lattice, due to dehydration, which provided key information
      relating RS solid-state form characteristics to final granulation moisture
      content. Final granulation moisture was found to have a significant effect on the
      change in RS hydration state measured by Raman spectroscopy. As the final
      granulation moisture decreased, the amount of RS dehydrated form increased. The
      largest Raman spectral changes were in the CH stretching region and the region
      including the 3-picoline ring and PO2- stretches. These changes are indicative of
      substantial changes in the RS solid-state structure. Final granulation moisture
      also had a significant effect on the change in tablet thickness over time. Lower
      final granulation moisture caused a greater increase in tablet thickness as the
      RS rehydrated. In addition, the change in RS hydration state during fluid bed
      drying, measured by on-line Raman, was correlated to the increase in tablet
      thickness and subsequent loss of tablet integrity. Raman spectroscopy allowed
      direct RS hydration state monitoring, rather than inference from a bulk moisture
      measurement. Development of a Process Analytical Technology (PAT), specifically
      Raman, to monitor RS solid-state during drying enabled establishment of
      relationships between fundamental hydration dynamics associated with RS and final
      product performance attributes.

PMID- 15979263
TI  - Release of DNA from dendriplexes encapsulated in PLGA nanoparticles.
AB  - Biodegradable PLGA particles of less than 1 microm can encapsulate DNA and DNA
      dendron complexes (dendriplexes) providing sustained DNA release for transfecting
      cells in gene delivery. Two polylysine-based dendrons prepared by solid state
      peptide synthesis were used to condense pRedN-1 DNA (7.5 kbp), a fluorescent
      protein vector. The dendrons had 16 free surface amino groups attached to seven
      lysine groups, bound to a lipid core, one containing three C18 chains and the
      other a single C10 chain. Increased lipophilicity and molar charge ratios are key
      factors in producing compact and reproducible dendriplexes, shown by the
      hydrodynamic diameter which is of the order of 800 nm (p.d.>0.5) at a 2:1 molar
      charge ratio, a value which decreases to around 200 nm at a 5:1 charge ratio. At
      lower charge ratios the dendriplexes are negative and have a zeta potential in
      order of -18 mV. As the ratio increases (5:1, 10:1) the complexes bear a positive
      potential (13+/-2 mV). This suggests that at the 2:1 ratio the DNA is not fully
      condensed. The DNA was radiolabelled with 35S dCTP (deoxycytidinetriphosphate)
      with the removal of the un-incorporated radiolabelled nucleotides. The
      encapsulation efficiency of dendriplexes in PLGA particles is higher than that
      for uncomplexed DNA. When the results are normalised for DNA content and particle
      surface area, complexation of the DNA was found to decrease release rate.

PMID- 15979264
TI  - Excipient effects on gastrointestinal transit and drug absorption in beagle dogs.
AB  - Previous work has shown that polyethylene glycol 400 (PEG 400) has an
      accelerating effect on gastrointestinal transit and a modulating influence on
      drug absorption in humans. The aim of this study was to assess the impact of
      various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene
      glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug
      absorption in four beagle dogs using scintigraphy. Each dog received, on five
      separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG
      400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and
      administered in the form of two capsules. The model drugs ampicillin (200mg) and
      antipyrine (100mg) were co-administered in the capsules. The capsule solutions
      were radiolabelled with technetium-99m to follow their transit using a dual
      headed gamma camera, and blood samples were collected to determine drug
      pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and
      given intravenously. The capsules rapidly disintegrated in the stomach liberating
      their liquid contents. The mean small intestinal transit times for the different
      treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183,
      179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral
      bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74,
      85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data
      for the excipient treatments were not significantly different from the control.
      In summary, these excipients, at the doses administered, have limited influence
      on gastrointestinal transit and drug in beagle dogs.

PMID- 15979265
TI  - Planned complex suicide: report of three cases.
AB  - This article presents three planned complex suicide cases. The first case was a
      46-year-old man, who had taken some antidepressant and antipsychotic drugs before
      cutting his right wrist and ingesting a large amount of concentrated hydrochloric
      acid. In the second case, a 34-year-old man was found dead in his home, hanging
      by his neck, with a suicidal stab wound on the left side of the chest. In the
      third case, a 22-year-old woman was found dead, hanging by her neck from a
      ceiling beam of her grandmother's a storage room, after taking of a solid
      rodenticide. The histories revealed psychiatric problems in all cases. The
      investigation of scene, the method employed, the autopsy findings and the
      interview with their relatives altogether pointed toward a suicidal etiology.

PMID- 15979266
TI  - Methamphetamine in hair and interpretation of forensic findings in a fatal case.
AB  - Hair analysis for drugs has been developing and is considered a significant tool
      for distinguishing between recent and long-term drug abuse in forensic and
      clinical toxicology. Chronic consumption of drugs can gradually induce certain
      harmful effects on the human organism and can exacerbate some pre-existing
      diseases. Analysis for drugs in blood or urine in isolation does not provide
      sufficient information about the history of drug-use by a person and their
      results cannot be correlated directly with the toxic effects displayed. The
      chronic abuse of methamphetamine is known to be associated with cardiovascular
      diseases. During or after autopsy certain types of morphologic alterations are
      found in the hearts of stimulant addicts. The rapid increase in blood pressure
      after an intravenous methamphetamine dose can be risky for addicts with
      arteriosclerosis. However, the anamnestic data about a deceased person may not
      always be available to explain the pathological findings and to classify the
      cause of death correctly. The aim of this study was to demonstrate the value of
      hair analysis for drugs in the context of explaining pathological cardiovascular
      alterations observed during the autopsy in a case where methamphetamine
      consumption was involved. In this case, only methamphetamine and metabolites were
      detected with traces of ephedrine. Ephedrine is the precursor chemical in the
      illicit synthesis of methamphetamine (known in the Czech Republic as "Pervitin").
      The femoral blood level of methamphetamine was 1500 ng/ml. It was documented by a
      witness that the 31-year-old man died within 1h after an intravenous injection of
      the drug. The cause of death was established as cerebral edema due to cerebellar
      bleeding shortly after an intravenous dose of methamphetamine. Findings of
      methamphetamine in the first three 2-cm hair segments (numbered from the roots)
      were nearly equal (132+/-9 ng/mg). In the fourth 2-cm segment, it was
      approximately one-half of previous values. In the remaining, distal 7-cm hair
      segment sample, the value of methamphetamine was higher and comparable to the
      third segment. These results provide clear evidence that the man had been a
      chronic methamphetamine abuser for more than 8 months. This information can help
      to explain the pathology, the consequence of which could be the bleeding into the
      cerebellum after the last single methamphetamine dose.

PMID- 15979267
TI  - Postnatal cerebellar defects in mice deficient in methylenetetrahydrofolate
      reductase.
AB  - Patients with severe deficiency of methylenetetrahydrofolate reductase (MTHFR)
      suffer from a wide variety of neurological problems, which can begin in the
      neonatal period. MTHFR is a critical enzyme in folate metabolism; the product of
      the MTHFR reaction, 5-methyltetrahydrofolate, is required for homocysteine
      remethylation to methionine and synthesis of S-adenosylmethionine (SAM). To
      understand the mechanisms by which MTHFR deficiency leads to significant
      neuropathology, we examined early postnatal brain development in mice with a
      homozygous knockout of the Mthfr gene. These mice displayed a dramatically
      reduced size of the cerebellum and cerebral cortex, with enlarged lateral
      ventricles. Mthfr deficiency affected granule cell maturation, but not
      neurogenesis. Depletion of external granule cells and disorganization of Purkinje
      cells were mainly confined to the anterior lobules of mutant cerebella. Decreased
      cellular proliferation and increased cell death contributed to the granule cell
      loss. Reduced expression of Engrailed-2 (En2), Reelin (Reln) and inositol 1,4,5
      triphosphate receptor type 1 (Itpr1) genes was observed in the cerebellum.
      Supplementation of Mthfr(+/-) dams with an alternate methyl donor, betaine,
      reduced cerebellar abnormalities in the Mthfr(-/-) pups. Our findings suggest
      that MTHFR plays a role in cerebellar patterning, possibly through effects on
      proliferation or apoptosis.

PMID- 15979268
TI  - Chemotherapy for colorectal cancer--an overview of current management for
      surgeons.
AB  - BACKGROUND: The role of systemic chemotherapy in the management of colorectal
      cancer has been re-evaluated with the advent of newer agents. The results of
      published trials are reviewed in this article and the protocols of some of the
      major ongoing trials outlined. METHODS: A medline based literature search was
      performed for articles relating to clinical trials using systemic chemotherapy in
      the management of colorectal cancer in the advanced and adjuvant setting.
      Additional original papers were obtained from citations in those identified by
      the initial search. RESULTS: The combination of irinotecan or oxaliplatin with 5
      fluorouracil (5-FU) based chemotherapy regimens for advanced cancer demonstrates
      better response rates when compared with 5-FU and folinic acid (FA). Although
      this translates into a modest survival benefit, it may increase resectability
      rates in patients with hepatic metastasis. Adjuvant chemotherapy in stage III
      cancer has been established to improve long-term survival although it is benefit
      for patients with stage II disease remains less clear. CONCLUSION: Evaluation of
      the various combinations of chemotherapeutic agents that are most effective and
      the clinical situations for which they are best suited is ongoing and will
      improve the current outlook for those with colorectal cancer.

PMID- 15979269
TI  - Improved survival in cancer of the colon and rectum in Sweden.
AB  - AIMS: To analyse time-trends in survival of patients with colon and rectal cancer
      in Sweden. PATIENTS AND METHODS: Data including all patients diagnosed with
      adenocarcinoma of the colon and rectum between 1960 and 1999, from the Swedish
      Cancer Registry, were analysed. The observed and relative survival rates were
      calculated according to the Hakulinen cohort method. RESULTS: Five-year relative
      survival rate for cancer of the colon improved significantly from 39.6% in 1960-
      1964 to 57.2% in 1995--1999 and for rectal cancer from 36.1 to 57.6%,
      respectively. Corresponding observed survival improved from 31.2 to 44.3% for
      colon cancer and from 28.4 to 45.4% for rectal cancer. The largest improvement of
      survival were seen during the later part of the period observed. CONCLUSION: The
      survival of patients with colon and rectal cancer in Sweden continues to improve,
      especially in rectal cancer, which now has a 5-year observed and relative
      survival rate comparable to that for colon cancer. The survival improvement in
      rectal cancer is probably a result of the implementation of total mesorectal
      excision and pre-operative radiotherapy.

PMID- 15979270
TI  - Evaluation of a breast cancer nomogram for prediction of non-sentinel lymph node
      positivity.
AB  - AIMS: This study evaluates the breast cancer nomogram (BCN), an online tool
      developed by Memorial Sloan-Kettering Cancer Center to determine the rate of non
      SLN positivity, in an independent cohort of SLN positive patients. MATERIAL AND
      METHODS: Available data between 02/2000 and 06/2004 in two prospective databases,
      749 cases had successful SLN biopsy including 149 axillary-SLN metastases study
      cases. These cases had accurately graded tumours up to 9 cm in size and CAD with
      a minimum total 10 nodes removed. Histopathological assessment of nodes included
      hematoxylin and eosin staining and/or immunohistochemistry. Computerized BCN was
      used to estimate probability of non-SLN positivity and compared with actual
      probability after grouping into deciles. RESULTS: The trend of actual probability
      in various decile groups was comparable to the predicted probability. An area
      under the receiver operating characteristic curve was 0.75 as compared to 0.76 in
      the original study. CONCLUSION: Although this study is small, the results are
      encouraging and suggest the nomogram is a useful tool to estimate the likelihood
      of positive axillary non-SLN. However, variations in pathological assessment
      between centres are the major impediment to widespread application of BCN. If SLN
      positive patients decline the standard recommendation of CAD or entry into
      clinical trials evaluating the significance of CAD then the BCN could help in
      decision making.

PMID- 15979271
TI  - Outcome after the introduction of a multimodality treatment program for locally
      advanced rectal cancer.
AB  - AIM: This prospective study reports the results of a multimodality treatment
      protocol in patients with locally advanced rectal cancer and assesses outcome
      after curative vs non-curative surgery and in relation to primary advanced vs
      locally recurrent cancer. METHODS: Between 1991 and 2002, 122 patients completed
      the protocol. Fifty-eight had primary advanced and sixty-four had locally
      recurrent rectal cancer. Median follow up was 82 months (5-143). RESULTS: A
      potentially curative resection was achieved in 59% of the patients with primary
      advanced and in 34% of patients with locally recurrent cancer. After curative
      resection, 53 and 59%, respectively, were free from recurrence during the
      observation time (median 82 months) and the overall 5-year survival was 34 and
      40%. Overall 5-year survival in all patients with primary advanced cancer was 29
      and 16% in all patients with locally recurrent rectal cancer. CONCLUSION:
      Multimodality treatment may cure at least a third of patients with locally
      advanced rectal cancer provided a radical resection is performed. As the post
      operative morbidity is high, an optimised patient selection for neo-adjuvant
      treatment and surgery is essential. However, palliative surgery may benefit the
      patient if local control is achieved. Future studies should focus on the problem
      of distant metastasis.

PMID- 15979272
TI  - Coordinate stabilization of growth-regulatory transcripts in T cell malignancies.
AB  - We used microarray technology to compare mRNA decay rates of approximately 7000
      transcripts in normal purified human T lymphocytes or the malignant T cell lines
      Jurkat and H9 following transcriptional arrest with actinomycin D. We found that
      over 2000 transcripts were expressed at abnormal levels in malignant T cells,
      including approximately 100 transcripts that were overexpressed and exhibited
      abnormally stable mRNA. Seventeen transcripts that encoded components of the
      ubiquitin-proteasome system were coordinately overexpressed and stabilized in
      both malignant cell lines. This pathway plays an important role in regulating
      cell growth and the development of malignancy. Numerous additional transcripts
      that encode proteins involved in growth regulation, damage repair and stress
      responses, posttranscriptional gene expression, and mitochondrial metabolism were
      also coordinately up-regulated and stabilized. Overall, our results suggest that
      abnormal mRNA stabilization in malignancy can lead to the overexpression of
      growth-regulatory genes and contribute to the malignant phenotype.

PMID- 15979273
TI  - Distribution of genes encoding the microbial non-oxidative reversible
      hydroxyarylic acid decarboxylases/phenol carboxylases.
AB  - Bacterial non-oxidative, reversible multi subunit hydroxyarylic acid
      decarboxylases/phenol carboxylases are encoded by the three clustered genes, B,
      C, and D, of approximately 0.6, 1.4, and 0.2 kb, respectively. There are more
      than 160 homologues in the database with significant similarity to gene B
      (homology to ubiX) and C (ubiD) distributed in all three microbial domains,
      however, homologues to gene D, are not numerous ( approximately 15). The
      occurrence of the entire BCD gene cluster encoding for either identified or
      presumptive hydroxyarylic acid decarboxylase to date has been revealed in
      Sedimentibacter hydroxybenzoicus (unique genes arrangement CDB), Streptomyces sp.
      D7, Bacillus subtilis, B. licheniformis, E. coli O157:H7, Klebsiella pneumoniae,
      Enterobacter cloacae, Shigella dysenteriae, Salmonella enterica, S. paratyphi, S.
      typhimurium, S. bongori, and S. diarizonae. The corresponding genes from S.
      hydroxybenzoicus, B. subtilis, Streptomyces sp. D7, E. coli O157:H7, K.
      pneumoniae, and S. typhimurium were cloned and expressed in E. coli DH5alpha
      (void of analogous genes), and shown to code for proteins exhibiting non
      oxidative hydroxyarylic acid decarboxylase activity.

PMID- 15979274
TI  - Chickenpox in pregnancy: revisited.
AB  - Varicella infection during the first and second trimester of pregnancy may
      increase the risk for congenital varicella syndrome 0.5-1.5% above the baseline
      risk for major malformation. Third trimester infection may lead to maternal
      pneumonia which can be life threatening if not treated appropriately. Varicella
      zoster immune globulin (VZIG) should be administered as soon as possible
      preferably within 96 h from exposure to prevent maternal infection or subsequent
      complications. Later than 96 h, the effectiveness of VZIG has not been evaluated.
      Neonatal varicella is more severe if maternal rash appears 5 days prior to or 2
      days after delivery. The newborn should be given VZIG immediately. Intravenous
      acyclovir is recommended for maternal pneumonia and severely affected neonate. No
      controlled study has yet evaluated the effectiveness of acyclovir or valacyclovir
      for postexposure prophylaxis to pregnant women or neonates. Unlike primary
      varicella infection in pregnancy, herpes zoster has not been documented to cause
      complications unless in the disseminated form. The advent of advanced imaging
      techniques and molecular biotechniques has improved prenatal diagnosis. With
      increase use of vaccination, the incidence of chickenpox in pregnancy is expected
      to decline in the future.

PMID- 15979275
TI  - Genetic diversity of Flavobacterium columnare examined by restriction fragment
      length polymorphism and sequencing of the 16S ribosomal RNA gene and the 16S-23S
      rDNA spacer.
AB  - Genetic variability among strains of Flavobacterium columnare, isolated in the
      United States, was characterized by restriction fragment length polymorphism
      (RFLP) and phylogenetic analysis based on the sequence of the 16S rRNA gene.
      Twenty-seven isolates of F. columnare were differentiated into three genotypes.
      The isolates within the genotypes were further grouped based on RFLP of the 16S
      23S rDNA spacer. The first genotype had five strains that were further divided
      into group A (4 strains) and B (1 strain) while the second genotype had 10
      strains that were also further divided into group A (4 strains) and B (6 stains).
      The third genotype had 12 isolates with no differences in the RFLP patterns of
      the 16S-23S rDNA spacers. The 16S rRNA gene sequences representing the three
      identified genotypes were compared to the different published sequences by
      phylogenetic analysis and the results showed the American genotypes 1, 2 and 3
      corresponding to genomovar 1, 2, and 3, respectively, reported by Triyanto and
      Wakabayashi [Triyanto, Wakabayashi H. Genotyping of strains of Flavobacterium
      columnare from diseased fishes. Fish Pathol 1999; 34: 65-71]. The study
      demonstrates a method for RFLP and sequencing of the 16S rRNA gene and the 16-23S
      rDNA spacer as a useful tool in epidemiological studies of F. columnare.

PMID- 15979276
TI  - Localization and altered expression of AKR1C family members in human ovarian
      tissues.
AB  - Relative expression of AKR1C family members and 5alphaR1 were determined using
      gene specific quantitative real-time PCR method. Both ARK1C1 and AKR1C2 were
      found significantly reduced in ovarian tumor tissues compared to ovarian normal
      tissues. In contrast, AKR1C3 and 5alphaR1 were kept the same transcriptional
      levels between ovarian tumor tissues and ovarian normal tissues.
      Immunohistochemical staining indicates that AKR1C1 shares the same localization
      with AKR1C3. Loss of ARK1C1 and AKR1C2 in ovarian cancerous tissues may enhance
      progesterone signaling in ovary itself by decreasing the ability of progesterone
      metabolism.

PMID- 15979277
TI  - Fundamental frequency histograms measured by electroglottography during speech: a
      pilot study for standardization.
AB  - This study was designed to develop a database for the electroglottographic
      measurement of fundamental frequency (Fo) in normal subjects in running speech,
      for reference in the diagnosis and follow-up of dysphonic patients. A prospective
      pilot study included 20 healthy male volunteers without laryngeal disorder.
      Electroglottographic recordings of speaking Fo during connected speech (French)
      were obtained from two texts with different prosodic content. Fo histograms were
      sensitive to the variation of speaking Fo between both texts. Graphic
      representation of the range and distribution of the Fo of the speaker were
      designed as normalized Fo histograms with plot lines at 5th and 95th percentiles.
      Less than 5% variability of Fo histograms was recorded when recording more than
      15 subjects. This pilot study designed a graphic display of standardized
      electroglottographic Fo measurements during the physiological condition of
      connected speech. As the degree of Fo variability depends on the phonetic
      contents of the text and on the language spoken, a separate histogram for normal
      subjects needs to be developed in each country or at least for each voice
      laboratory, with a standard, previously chosen text.

PMID- 15979278
TI  - Autonomous detection of pulmonary nodules on CT images with a neural network
      based fuzzy system.
AB  - In this paper, a novel extension of neural network-based fuzzy model has been
      proposed to detect lung nodules. The proposed model can automatically identify a
      set of appropriate fuzzy inference rules, and refine the membership functions
      through the steepest gradient descent-learning algorithm. Twenty-nine clinical
      cases involving 583 thick section CT images were tested in this study. Receiver
      operating characteristic (ROC) analysis was used to evaluate the proposed
      autonomous pulmonary nodules detection system and yielded an area under the ROC
      curve of Azs=0.963. The overall detection sensitivity of the proposed method was
      89.3% (with p-value less than 0.001), and the false positive was as low as 0.2
      per image. This result demonstrates that the proposed neural network-based fuzzy
      system resolves the most suitable fuzzy rules, improves the detection rate, and
      reduces false positives compared to other approaches. The proposed system is
      fully automated with fast processing speed. The studies have shown a high
      potential for implementation of this system in clinical practice as a CAD tool.

PMID- 15979279
TI  - Activation of muscarinic M4 receptor augments NGF-induced pro-survival Akt
      signaling in PC12 cells.
AB  - Survival or death of neurons during development is mediated by the integration of
      a diverse array of signal transduction cascades that are controlled by the
      availability and acquisition of neurotrophic factors and agonists acting at G
      protein-coupled receptors (GPCRs). Recent studies have demonstrated that GPCRs
      can modulate signals elicited by receptor tyrosine kinases (RTK) and vice versa.
      Here, we examined the activity of pro-survival Akt kinase, in response to
      stimulation by muscarinic acetylcholine receptors (mAChRs) and co-activation with
      the nerve growth factor (NGF) receptor in PC12 cells endogenously expressing Gi
      coupled M4 mAChR and Gq-coupled M1 and M5 mAChRs. Western blotting analysis using
      a phosphospecific anti-Akt antibody revealed a dose- and time-dependent increase
      in Akt phosphorylation in cells stimulated with mAChR specific agonist carbachol
      (CCh). Co-stimulation with CCh and NGF resulted in augmentation of Akt activity
      in a pertussis toxin (PTX)-sensitive manner, suggesting that M4 mAChR, but not M1
      and M5 mAChRs, was associated with this synergistic Akt activation. The use of
      transducin as a Gbetagamma scavenger indicated that Gbetagamma subunits rather
      than Galphai/o acted as the signal transducer. Additional experiments showed that
      CCh treatment augmented NGF-induced phosphorylation and degradation of the Akt
      regulated translation regulator tuberin. This augmentation was also inhibited by
      PTX pre-treatment or overexpression of transducin. Finally, co-stimulation of
      PC12 cells with CCh and NGF resulted in enhancement of cell survival. This is the
      first study that demonstrates the augmentation effect between M4 mAChR and NGF
      receptor, and the regulatory role of mAChR on tuberin.

PMID- 15979280
TI  - Physiological levels of PTEN control the size of the cellular Ins(1,3,4,5,6)P(5)
      pool.
AB  - To understand how a signaling molecule's activities are regulated, we need
      insight into the processes controlling the dynamic balance between its synthesis
      and degradation. For the Ins(1,3,4,5,6)P5 signal, this information is woefully
      inadequate. For example, the only known cytosolic enzyme with the capacity to
      degrade Ins(1,3,4,5,6)P5 is the tumour-suppressor PTEN [J.J. Caffrey, T. Darden,
      M.R. Wenk, S.B. Shears, FEBS Lett. 499 (2001) 6 ], but the biological relevance
      has been questioned by others [E.A. Orchiston, D. Bennett, N.R. Leslie, R.G.
      Clarke, L. Winward, C.P. Downes, S.T. Safrany, J. Biol. Chem. 279 (2004) 1116 ].
      The current study emphasizes the role of physiological levels of PTEN in
      Ins(1,3,4,5,6)P5 homeostasis. We employed two cell models. First, we used a human
      U87MG glioblastoma PTEN-null cell line that hosts an ecdysone-inducible PTEN
      expression system. Second, the human H1299 bronchial cell line, in which PTEN is
      hypomorphic due to promoter methylation, has been stably transfected with
      physiologically relevant levels of PTEN. In both models, a novel consequence of
      PTEN expression was to increase Ins(1,3,4,5,6)P5 pool size by 30-40% (p<0.01);
      this response was wortmannin-insensitive and, therefore, independent of the
      PtdIns 3-kinase pathway. In U87MG cells, induction of the G129R catalytically
      inactive PTEN mutant did not affect Ins(1,3,4,5,6)P(5) levels. PTEN induction did
      not alter the expression of enzymes participating in Ins(1,3,4,5,6)P5 synthesis.
      Another effect of PTEN expression in U87MG cells was to decrease InsP6 levels by
      13% (p<0.02). The InsP6-phosphatase, MIPP, may be responsible for the latter
      effect; we show that recombinant human MIPP dephosphorylates InsP6 to D/L
      Ins(1,2,4,5,6)P5, levels of which increased 60% (p<0.05) following PTEN
      expression in U87MG cells. Overall, our data add higher inositol phosphates to
      the list of important cellular regulators [Y. Huang, R.P. Wernyj, D.D. Norton, P.
      Precht, M.C. Seminario, R.L. Wange, Oncogene, 24 (2005) 3819 ] the levels of
      which are modulated by expression of the highly pleiotropic PTEN protein.

PMID- 15979281
TI  - Measurement of net acid excretion by use of paper strips.
AB  - OBJECTIVE: Net endogenous acid production, reflected in the steady state as net
      acid excretion (NAE), is implicated in bone loss because it is positively
      associated with urinary calcium loss. Protein is one of the main sources of
      dietary acid load, whereas fruit and vegetables provide alkaline potassium salts
      that counteract the dietary acid load. This study investigated whether a pH paper
      strip measurement of overnight (i.e., first void) urine would reflect 24-h NAE,
      measured as excretion rates of titratable acid minus bicarbonate plus ammonium.
      METHODS: Twenty-three subjects collected 24-h urine in two parts: day
      (approximately 7 am to 11 pm) and overnight (approximately 11 pm to 7 am). At
      first void, subjects recorded pH using paper strips. Subjects recorded intake and
      20 subjects provided fasting urine collected from 7 to 9 am. RESULTS: The pH
      paper strip measurements of first void urine was significantly correlated with 24
      h titratable acid minus bicarbonate (r = -0.466, P < 0.025) but not with 24-h
      NAE. We examined the association of dietary protein, potassium, protein:potassium
      ratio, and sodium with NAE, with fasting morning urinary calcium excretion, an
      indirect measurement of bone loss, and with urinary cross-links, a direct
      measurement of bone resorption. Of these, only sodium intake (measured as 24-h
      urine excretion) and urine potassium:sodium ratio showed a significant relation
      (with fasting calcium excretion). CONCLUSIONS: We did not find that the first
      void urine pH by paper strip measurement provided an index of daily net
      endogenous acid production as reflected in 24-h NAE. In our sample of young
      adults, daily sodium intake positively correlated with bone resorption, as
      reflected in fasting urine calcium, whereas daily NAE did not.

PMID- 15979282
TI  - Melatonin in walnuts: influence on levels of melatonin and total antioxidant
      capacity of blood.
AB  - OBJECTIVE: We investigated whether melatonin is present in walnuts (Juglans regia
      L.) and, if so, tested whether eating walnuts influences melatonin levels and the
      total antioxidant status of the blood. METHODS: Melatonin was extracted from
      walnuts and quantified by high-performance liquid chromatography. After feeding
      walnuts to rats, serum melatonin concentrations were measured using a
      radioimmunoassay and the "total antioxidant power" of the serum was estimated by
      using the trolox equivalent antioxidant capacity and ferric-reducing ability of
      serum methods. RESULTS: Mean +/- standard error melatonin concentrations were 3.5
      +/- 1.0 ng/g of walnut. After food restriction of rats and then feeding them
      regular chow or walnuts, blood melatonin concentrations in the animals that ate
      walnuts were increased over those in the rats fed the control diet. Increases in
      blood melatonin were also accompanied by increases in trolox equivalent
      antioxidant capacity and ferric-reducing ability of serum values. CONCLUSIONS:
      Melatonin is present in walnuts and, when eaten, increase blood melatonin
      concentrations. The increase in blood melatonin levels correlates with an
      increased antioxidative capacity of this fluid as reflected by augmentation of
      trolox equivalent antioxidant capacity and ferric-reducing ability of serum
      values.

PMID- 15979283
TI  - Patients with severe bowel malabsorption do not have changes in iodine status.
AB  - OBJECTIVE: We evaluated the influence of intestinal malabsorption on iodine
      status in patients who had short gut syndrome and received total parenteral
      nutrition (group I) compared with control subjects who had eutrophia (group II)
      and patients who had other illnesses but normal digestive tracts (group III).
      METHODS: Twenty-seven subjects were studied. Iodine intake was determined by the
      measurement of iodine in ingested food and in parenteral nutrition solutions.
      Urinary iodine excretion was measured by the Sandell-Kalthoff reaction. Urinary
      creatinine, anthropometric, and thyroid hormone functions were also determined.
      RESULTS: Daily iodine intakes were 658 +/- 125 (mean +/- standard deviation), 573
      +/- 204, and 629 +/- 208 microg for groups I, II, and III, respectively. Daily
      urinary iodine excretion levels were 399 +/- 308, 439 +/- 192, and 370 +/- 268
      microg and ratios of urinary iodine (micrograms) to creatinine (grams) were 614
      +/- 349, 354 +/- 142, and 483 +/- 292, respectively. There were no statistically
      significant differences across groups. CONCLUSION: In Brazil the iodine provided
      by food, including iodized salt, has been sufficient to maintain iodine status in
      patients with short gut syndrome.

PMID- 15979284
TI  - Thiamine deficiency and beriberi features in a patient with hyperemesis
      gravidarum.
AB  - Wernicke's encephalopathy has been sporadically reported in patients with severe
      hyperemesis gravidarum. We report a new case of Wernicke's encephalopathy in a
      patient who had hyperemesis gravidarum associated with signs and symptoms of dry
      and wet beriberi. The case was managed with very large doses of thiamine. The
      conclusion was that, in long-lasting hyperemesis gravidarum, recognizing signs of
      beriberi may help prevent the onset of Wernicke's encephalopathy, thanks to
      timely therapy with thiamine supplements. A thiamine therapy similar to the one
      reported in this article could prove useful in long-lasting hyperemesis
      gravidarum complicated by Wernicke's encephalopathy.

PMID- 15979285
TI  - Head and neck manifestations of myeloma in Nigerians.
AB  - A study on the clinicopathologic features of myeloma as it manifests in the head
      and neck region was conducted over a 15-year period. A total of six patients were
      seen and they constituted 20% of all myeloma cases. The mean age was 41.5 years,
      three were males and three were females. Clinical presentation was varied and
      included swelling, epistaxis and gingival bleeding. The duration of symptom
      ranged from 3 months to 6 years. Definitive diagnosis was extramedullary
      myelomatosis in three patients, multiple myeloma in two patients while one
      patient had solitary plasmacytoma of bone. Chemotherapy alone was the treatment
      modality in two patients, one had surgery combined with chemotherapy and one
      patient had only supportive therapy. Two patients did not receive treatment, as
      they requested for discharge against medical advice. One patient followed up for
      a period of 1 year recovered with residual neurological deficits. This study
      confirms the rarity of myeloma in the head and neck region and where it occurs;
      it is most likely multiple myeloma or extramedullary myelomatosis. In this part
      of the world, mortality rate is aggravated by late presentation and inability to
      afford chemotherapy.

PMID- 15979286
TI  - Sequential changes of nitric oxide levels in the temporal lobes of kainic acid
      treated mice following application of nitric oxide synthase inhibitors and
      phenobarbital.
AB  - Although studies have indicated a close relationship between nitric oxide (NO)
      and kainic acid (KA)-induced seizures, the role of NO in seizures is not fully
      understood. Here, we quantified NO levels in the brain of KA-treated mice using
      EPR spectrometry to elucidate the role of NO in KA-induced seizures. KA was
      administered to mice with or without pretreatment with one of the following: N(G)
      nitro-l-arginine methyl ester (l-NAME), an NO synthase (NOS) inhibitor that acts
      on both endothelial NOS (eNOS) and neuronal NOS (nNOS); 7-nitroindazole (7-NI),
      which acts more selectively on nNOS in vivo; or the anti-epileptic drug,
      phenobarbital. To accurately assess NO production during seizure activity, we
      directly measured KA-induced NO levels in the temporal lobe using an electron
      paramagnetic resonance NO trapping technique. Our results revealed that the both
      dose- and time-dependent changes of NO levels in the temporal lobe of KA-treated
      mice were closely related to the development of seizure activity. l-NAME mediated
      suppression of the KA-induced NO generation led to enhanced severity of KA
      induced seizures. In contrast, 7-NI induced only about 50% suppression and had
      little effect on seizure severity; while phenobarbital markedly reduced both NO
      production and seizure severity. These results show that KA-induced
      neuroexcitation leads to profound increases in NO release to the temporal lobe of
      KA-treated mice and that NO generation from eNOS exerts an anti-convulsant
      effect.

PMID- 15979287
TI  - Review of longitudinal functional neuroimaging studies of drug treatments in
      patients with schizophrenia.
AB  - We systematically reviewed twenty-one functional neuroimaging studies that used
      longitudinal designs to investigate the effects of medication treatments on brain
      functioning among patients with schizophrenia. The studies reviewed were
      comprised of functional magnetic resonance imaging and positron emission
      tomography research using a baseline and at least one follow-up. The present
      review summarizes the different effects of medication and disease status on brain
      function, with attention to functional normalization, specific drug effects, and
      comparisons of typical versus atypical antipsychotics. Particular emphasis is
      given to methodological limitations in the existing literature, including lack of
      reliability data, clinical heterogeneity among studies, and inadequate study
      designs and statistics. Suggestions are made for improving future longitudinal
      neuroimaging studies of treatment effects in schizophrenia.

PMID- 15979288
TI  - The accumulation of phytoalexin in cucumber plant after stress.
AB  - During the course of pathogens penetrating the plant cell, besides of chemical
      secretion, the pathogens may cause mechanical signal by the physical pressure on
      the plant cell. In the current study, we use the pressure as the stress signal to
      study the induction in plant resistance and the effect of accumulation of
      phytoalexin. We found that stress can induce the resistance in cucumber seeding
      significantly. Peptides contained RGD motif can specific block the adhesion
      between plant cell wall and plasma membrane. When breaking the plant cell wall
      and plasma membrane by using RGD peptides, the stress induction effect is almost
      absolutely eliminated. The results of assay with TLC and HPLC showed that stress
      stimulation could increase the accumulation of cucumber seeding phytoalexin. So,
      we can conclude that the accumulation of phytoalexin is one possible reason of
      improve the stress induced resistance. When block the adhesion between plant cell
      wall and plasma membrane by RGD, there are only part of accumulation of
      phytoalexin. The results suggest that stress induced resistance and accumulation
      of phytoalexin of plant is required for the adhesion of plant cell wall-plasma
      membrane.

PMID- 15979289
TI  - Effect of poly(ethylene oxide) on the release behaviors of poly(epsilon
      caprolactone) microcapsules containing erythromycin.
AB  - The biodegradable poly(epsilon-caprolactone) (PCL)/poly(ethylene oxide) (PEO)
      microcapsules and the analyzing of form and features for the manufacturing
      conditions were investigated in a prospective drug delivery systems (DDS) through
      drug release. The effects of emulsifier, emulsifier concentration, and stirring
      rate on the diameter and form of the microcapsules were examined using image
      analyzer (IA) and scanning electron microscope (SEM). The role of interfacial
      adhesion between PCL/PEO and drug was determined by contact angle measurements,
      and the drug release rate of the microcapsules was characterized by UV-vis
      spectroscopy. As a result, the microcapsules were made in spherical forms with a
      mean particle size of 170 nm approximately 68 microm. And the work of adhesion
      between water and PCL/PEO was increased with increasing the PEO content, which is
      due to higher hydrophilicity of PEO. The drug release rate of the microcapsules
      was significantly increased as the PEO content increased, which could be
      attributed to the increasing of the hydrophilic groups or the degree of adhesion
      at the interfaces.

PMID- 15979290
TI  - [Prevention of neonatal tetanus in Congo Brazzaville].

PMID- 15979291
TI  - Machine recognition and representation of neonatal facial displays of acute pain.
AB  - OBJECTIVE: It has been reported in medical literature that health care
      professionals have difficulty distinguishing a newborn's facial expressions of
      pain from facial reactions to other stimuli. Although a number of pain
      instruments have been developed to assist health professionals, studies
      demonstrate that health professionals are not entirely impartial in their
      assessment of pain and fail to capitalize on all the information exhibited in a
      newborn's facial displays. This study tackles these problems by applying three
      different state-of-the-art face classification techniques to the task of
      distinguishing a newborn's facial expressions of pain. METHODS: The facial
      expressions of 26 neonates between the ages of 18 h and 3 days old were
      photographed experiencing the pain of a heel lance and a variety of stressors,
      including transport from one crib to another (a disturbance that can provoke
      crying that is not in response to pain), an air stimulus on the nose, and
      friction on the external lateral surface of the heel. Three face classification
      techniques, principal component analysis (PCA), linear discriminant analysis
      (LDA), and support vector machine (SVM), were used to classify the faces.
      RESULTS: In our experiments, the best recognition rates of pain versus nonpain
      (88.00%), pain versus rest (94.62%), pain versus cry (80.00%), pain versus air
      puff (83.33%), and pain versus friction (93.00%) were obtained from an SVM with a
      polynomial kernel of degree 3. The SVM outperformed two commonly used methods in
      face classification: PCA and LDA, each using the L1 distance metric. CONCLUSION:
      The results of this study indicate that the application of face classification
      techniques in pain assessment and management is a promising area of
      investigation.

PMID- 15979292
TI  - Increased osteoblastogenesis and decreased bone resorption protect against
      ovariectomy-induced bone loss in thrombospondin-2-null mice.
AB  - Although bone is composed primarily of extracellular matrix (ECM), the dynamic
      role that the ECM plays in regulating bone remodeling secondary to estrogen loss
      is relatively unexplored. Previous studies have shown that mice deficient in the
      matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone;
      thus, we postulated that enhanced bone formation in TSP2-null mice could protect
      against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a
      significant loss of both midfemoral endocortical and proximal tibial trabecular
      bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed
      an increase in bone formation, as indicated by a 70% increase in serum
      osteocalcin two weeks post OVX and a two-fold increase in bone formation rate
      (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals
      showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR
      at five weeks. This increase in bone formation in TSP2-null OVX mice was
      accompanied by a three-fold increase in osteoprogenitor number. Although these
      results provide a partial explanation for the maintenance of bone geometry post
      OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level
      of bone resorption than OVX WT mice, as determined by serum levels of the amino
      terminal telopeptide of type I collagen (NTx). We conclude that the absence of
      TSP2 protects against OVX-induced bone loss by two complementary processes:
      increased formation and decreased resorption.

PMID- 15979293
TI  - Lipoxin analogs and lipoxin formation in vivo.
AB  - The definition of lipoxin bioactions in vivo and of lipoxin levels in humans,
      under physiological and pathological conditions, represents a main task toward
      the clinical use of lipoxins. The introduction of lipoxin stable analogs and of
      new methodology for immunological measurements of lipoxin A4 in human fluids is
      significantly contributing to fulfill this task. This chapter reviews the current
      literature on the use of lipoxin analogs, in vivo, and on measurements of lipoxin
      A4 in health and disease.

PMID- 15979294
TI  - Lipid mediator networks and leukocyte transmigration.
AB  - In intact tissues, vascular endothelial cells lie anatomically positioned as the
      central coordinator of inflammation. Endothelia communicate with underlying cells
      (e.g. smooth muscle, fibroblasts, epithelia) in ways that both coordinate
      leukocyte trafficking, and control the composition of the inflammatory
      microenvironment. Such coordination occurs through both direct communication
      (e.g. cell adhesion) as well as via soluble mediators liberated at sites of
      inflammation (e.g. chemokines, cytokines, lipids). Locally generated mediators
      bind to surface receptors, and mediate both physiologic and pathophysiologic
      functional responses. Important in this regard, both endothelial and
      subendothelial cell populations express enzymes capable of utilizing arachidonic
      acid substrates to generate bioactive lipid mediators (e.g. lipoxygenases,
      cyclooxygenases). Such lipid mediators can signal via autocrine or paracrine
      pathways and, depending on the tissue microenvironment, can convey a pro- or anti
      inflammatory message. This review will highlight recent studies characterizing
      inflammatory responses to lipid mediators liberated at sites of inflammation,
      with a particular emphasis on neutrophil (polymorphonuclear leukocyte or PMN)
      trafficking.

PMID- 15979295
TI  - Lipoxins in the eye and their role in wound healing.
AB  - The eye must contain highly evolved programs to limit inflammation and promote
      wound healing as an errant response can lead to blindness. However, pathways that
      protect the delicate visual axis and account for its atypical inflammatory
      responses remain to be clearly defined. Hence, research efforts have been
      initiated to elucidate the role of the anti-inflammatory LXA4 circuits in the
      eye. LXA4 is formed in healthy and injured corneas and both its receptor and
      12/15-lipoxygenase are predominantly expressed in epithelial cells. An essential
      role for LXA4 in preserving ocular function is supported by 12/15-LOX deficient
      mice that exhibit a phenotype of impaired wound healing and LXA4 formation. A
      novel epithelial bioaction role for LXA4 has been uncovered in the cornea as
      topical LXA4 promotes wound healing and limits the sequelae of injury. These
      emerging studies indicate that the LXA4 circuit may hold a fundamental role in
      maintaining an ocular environment that actively restricts inflammation while
      promoting wound healing.

PMID- 15979297
TI  - Heavy metal release from different ashes during serial batch tests using water
      and acid.
AB  - Most ashes contain a significant amount of heavy metals and when released from
      disposed or used ash materials, they can form a major environmental concern for
      underground waters. The use of water extracts to assess the easily mobilisable
      content of heavy metals may not provide an appropriate measure. This study
      describes the patterns of heavy metal release from ash materials in context with
      results from the German standard extraction method DIN-S4 (DIN 38 414 S4).
      Samples of four different ashes (municipal solid waste incineration ash, wood
      ash, brown coal ash and hard coal ash) were subjected to a number of serial batch
      tests with liquid renewal, some of which involved the addition of acid to
      neutralize carbonates and oxides. Release of heavy metals showed different
      patterns depending on the element, the type of material, the method of extraction
      and the type of the extractant used. Only a small fraction of the total heavy
      metal contents occurred as water soluble salts; of special significance was the
      amount of Cr released from the wood ash. The reaction time (1, 24 or 72 h between
      each extraction step with water) had only a small effect on the release of heavy
      metals. However, the release of most of the heavy metals was governed by the
      dissolution processes following proton inputs, indicating that pH-dependent tests
      such as CEN TC 292 or others are required to estimate long-term effects of heavy
      metal releases from ashes. Based on the chemical characteristics of ash materials
      in terms of their form and solubility of heavy metals, recommendations were made
      on the disposal or use of the four ash materials.

PMID- 15979298
TI  - Characterization and possible uses of ashes from wastewater treatment plants.
AB  - This work, on the ashes from the wastewater treatment plant of Galindo (Vizcaya,
      Spain), has been outlined with the purpose of finding their physico-chemical
      properties and suggesting possible applications. Ashes contain important
      quantities of iron, calcium, silica, alumina and phosphates. X-Ray diffraction
      data make it possible to estimate the mineralogical compositions of the original
      ashes and also, after thermal treatment at 1200 and 1300 degrees C, the main
      reactions occurring in thermal treatment. Particle size analysis makes it
      possible to classify ashes as a very fine powdered material. The thermal
      treatment leads to a densification of the material and provokes losses of weight
      mainly due to the elimination of water, carbon dioxide and sulphur trioxide.
      Application tests show that ashes are not suitable for landfill and similar
      applications, because of their plastic properties. Testing for pozzolanic
      character, after the ashes had been heated at 1200 degrees C, did not lead to a
      strong material probably due to low contents in silica and alumina or to
      requiring a higher heating temperature. Thermal treatment leads to densification
      of the material with a considerable increase of compressive strength of the
      probes. The use of additives (clays and powdered glass) to improve ceramic
      properties of ashes will be the aim of a future work.

PMID- 15979299
TI  - Molecularly imprinted thin film self-assembled on piezoelectric quartz crystal
      surface by the sol-gel process for protein recognition.
AB  - A novel method of combining sol-gel and self-assembly technology to prepare a
      human serum albumin (HSA)-imprinted film on the surface of piezoelectric quartz
      crystal (PQC) Au-electrode modified with thioglycolic acid was described in this
      paper. The imprinting process was characterized by using the piezoelectric quartz
      crystal impedance (PQCI) technique and electrochemical impedance technique.
      Scanning electron microscope (SEM) was employed to characterize the surface
      morphology of the resultant imprinted film. The piezoelectric technique and
      electrochemical impedance technique were also employed to investigate the binding
      performance of the sol-gel-imprinted film with the template protein. The results
      showed that the imprinted PQC film can give selective recognition to the template
      protein. The effects of salts and solvents on the binding capacity of the
      imprinted film with protein were discussed in detail. Other influencing factors
      (temperature and pH) have also been investigated. This self-assembly sol-gel
      imprinting technique was proved to be an alternative method for the preparation
      of biomacromolecule-imprinted thin film.

PMID- 15979300
TI  - Parallels between the proximal-distal development of vertebrate and arthropod
      appendages: homology without an ancestor?
AB  - Evolutionary studies suggest that the limbs of vertebrates and the appendages of
      arthropods do not share a common origin. However, recent genetic studies show new
      similarities in their developmental programmes. These similarities might be
      caused by the independent recruitment of homologous genes for similar functions
      or by the conservation of an ancestral proximal-distal development programme.
      This basic programme might have arisen in an ancestral outgrowth and been
      independently co-opted in vertebrate and arthropod appendages. It has
      subsequently diverged in both phyla to fine-pattern the limb and to control
      phylum-specific cellular events. We suggest that although vertebrate limbs and
      arthropod appendages are not strictly homologous structures they retain remnants
      of a common ancestral developmental programme.

PMID- 15979301
TI  - Globalisation reaches gene regulation: the case for vertebrate limb development.
AB  - Analysis of key regulators of vertebrate limb development has revealed that the
      cis-regulatory regions controlling their expression are often located several
      hundred kilobases upstream of the transcription units. These far up- or down
      stream cis-regulatory regions tend to reside within rather large, functionally
      and structurally unrelated genes. Molecular analysis is beginning to reveal the
      complexity of these large genomic landscapes, which control the co-expression of
      clusters of diverse genes by this novel type of long-range and globally acting
      cis-regulatory region. An increasing number of spontaneous mutations in
      vertebrates, including humans, are being discovered inactivating or altering such
      global control regions. Thereby, the functions of a seemingly distant but
      essential gene are disrupted rather than the closest.

PMID- 15979302
TI  - Pattern formation and developmental mechanisms: good mileage from comparative
      studies in cell biology, gene regulation, development and evolution.

PMID- 15979303
TI  - MicroRNAs in vertebrate development.
AB  - The vertebrate genome contains hundreds of small non-coding 'microRNAs' that have
      been implicated in controlling the expression of potentially thousands of target
      genes. Presently, only a handful of these targets have been characterized. Recent
      reports of microRNA 'sensors', microRNA microarrays and the creation of
      vertebrates that lack all microRNA activity will aid in determining the roles
      played by microRNAs, and the genes that they regulate, during vertebrate
      development.

PMID- 15979304
TI  - Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer.
AB  - Insulin and insulin-like growth factors (IGFs) have critical functions in growth
      regulatory signalling pathways. They are part of a tightly controlled network of
      ligands, receptors, binding proteins and their proteases. However, the system
      becomes uncontrolled in neoplasia. The insulin-like growth factor binding protein
      3 (IGFBP-3) and the insulin-like growth factor binding protein-related protein 1
      (IGFBP-rP1) have unique properties among the sixteen known members of the IGFBP
      superfamily. IGFBP-3 has very high affinity for IGFs (k(d) approximately 10(-10)
      M), it transports >75% of serum IGF-I and -II, whereas it's affinity for insulin
      is very low. On the other hand, IGFBP-rP1 binds insulin with very high affinity
      (500-fold higher compared to other IGFBPs), but has low affinity for IGF-I and 
      II proteins (k(d) = 3 x 10(-8) M). In this review, we have examined the roles of
      IGFBP-3 and IGFBP-rP1 in breast cancer, and discuss the potential impact of these
      two proteins in mammary carcinoma risk assessment and the development of
      treatments for breast cancer.

PMID- 15979305
TI  - Strategies to improve outcomes of children with cancer in low-income countries.

PMID- 15979306
TI  - Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and
      sex steroid receptors in the rat vagina.
AB  - To assess the specific estrogenic and/or androgenic effects of a potential novel
      hormone replacement therapy, we have examined the morphology of the rat vagina 9
      months after ovariectomy (OVX) and treatment of OVX animals with
      dehydroepiandrosterone (DHEA), conjugated estrogens Premarin and the selective
      estrogen receptor modulator Acolbifene. OVX led to atrophy and inflammatory
      changes while Acolbifene reduced the inflammation incidence and induced
      mucification of the vaginal epithelium. Premarin induced a typical keratinized
      stratified squamous epithelium while DHEA induced stimulation of the vaginal
      epithelium, with mucous cells typical of an androgenic effect, combined with
      increased collagen fiber compactness of the lamina propria. On the other hand,
      after OVX, the vaginal muscle layer decreased by 46%, an effect which was 41 and
      100% reversed by DHEA and Premarin, respectively. The present data show
      particularly interesting effects of DHEA on the three layers of the vaginal wall,
      namely a highly mucified epithelium, an increased muscularis thickness and
      increased collagen fiber compactness in the lamina propria. DHEA exerts both
      androgenic and estrogenic effects on the vaginal mucosa, thus providing a more
      physiological replacement therapy.

PMID- 15979307
TI  - Comparison of phytase production on wheat bran and oilcakes in solid-state
      fermentation by Mucor racemosus.
AB  - Comparisons were made for phytase production using wheat bran (WB) and oilcakes
      as substrates in solid-state fermentation (SSF) by Mucor racemosus NRRL 1994. WB
      was also used as mixed substrate with oil cakes. Sesame oil cake (SOC) served as
      the best carbon source for phytase synthesis by the fungal strain as it gave the
      highest enzyme titres (30.6 U/gds). Groundnut oil cake (GOC) also produced a
      reasonably good quantity of enzyme (24.3 U/gds). Enzyme production on WB was
      surprisingly much less (almost 3.5 times less in comparison to SOC). Mixing WB
      with SOC (1:1 ratio) resulted in better phytase activity (32.2 U/gds).
      Optimization of various process parameters such as incubation time, initial
      moisture content and inoculum concentration was carried out using the single
      variable mode optimization technique. Under optimized conditions, the production
      of phytase reached 44.5 U/gds, which was almost 1.5-fold higher than the highest
      yield obtained with any individual substrate used in this study and was more than
      4-fold higher than that obtained from WB.

PMID- 15979308
TI  - Reduction of indicator and pathogenic microorganisms by psychrophilic anaerobic
      digestion in swine slurries.
AB  - The objective of this study was to evaluate the efficiency of a low temperature
      anaerobic treatment to reduce viable populations of indicator microorganisms
      (total coliforms, Escherichia coli) and the presence of selected pathogens
      (Salmonella, Yersinia enterocolitica, Cryptosporidium and Giardia) in swine
      slurries from different sources. Experiments were carried out in 40 l Sequencing
      Batch Reactors (SBRs). Experimental results indicated that anaerobic digestion of
      swine manure slurry at 20 degrees C for 20 days in an intermittently fed SBR: (1)
      reduced indigenous populations of total coliforms by 97.94-100%; (2) reduced
      indigenous populations of E. coli by 99.67-100%; (3) resulted in undetectable
      levels of indigenous strains of Salmonella, Cryptosporidium, and Giardia. It can
      be considered as a promising method for reducing indigenous indicator and
      pathogenic microorganisms populations in liquid swine manure slurries.

PMID- 15979309
TI  - Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles.
AB  - 1-Glycosyl-4-phenyl triazoles have been prepared via a copper-mediated [3+2]
      cycloaddition of glycosyl azides with phenylacetylene. These triazoles have been
      evaluated for their ability to inhibit the enzymatic activity of glycosidases.

PMID- 15979311
TI  - Differential suppression of seizures via Y2 and Y5 neuropeptide Y receptors.
AB  - Neuropeptide Y (NPY) prominently inhibits epileptic seizures in different animal
      models. The NPY receptors mediating this effect remain controversial partially
      due to lack of highly selective agonists and antagonists. To circumvent this
      problem, we used various NPY receptor knockout mice with the same genetic
      background and explored anti-epileptic action of NPY in vitro and in vivo. In Y2
      (Y2-/-) and Y5 (Y5-/-) receptor knockouts, NPY partially inhibited 0 Mg2+-induced
      epileptiform activity in hippocampal slices. In contrast, in double knockouts
      (Y2Y5-/-), NPY had no effect, suggesting that in the hippocampus in vitro both
      receptors mediate anti-epileptiform action of NPY in an additive manner. Systemic
      kainate induced more severe seizures in Y5-/- and Y2Y5-/-, but not in Y2-/- mice,
      as compared to wild-type mice. Moreover, kainate seizures were aggravated by
      administration of the Y5 antagonist L-152,804 in wild-type mice. In Y5-/- mice,
      hippocampal kindling progressed faster, and afterdischarge durations were longer
      in amygdala, but not in hippocampus, as compared to wild-type controls. Taken
      together, these data suggest that, in mice, both Y2 and Y5 receptors regulate
      hippocampal seizures in vitro, while activation of Y5 receptors in extra
      hippocampal regions reduces generalized seizures in vivo.

PMID- 15979312
TI  - Apolipoprotein E4 enhances brain inflammation by modulation of the NF-kappaB
      signaling cascade.
AB  - Apolipoprotein E4 (apoE4), the major genetic risk factor of Alzheimer's disease
      (AD), is associated with enhanced brain inflammation. Genome-wide gene expression
      profiling was employed to study the effects of apoE genotype on hippocampal gene
      expression in LPS-treated mice, transgenic for either apoE4 or the AD benign
      allele, apoE3. This revealed that the expression of inflammation-related genes
      following intracerebroventricular injection of LPS was significantly higher and
      more prolonged in apoE4 than in apoE3 transgenic mice. Clustering analysis
      revealed gene clusters which responded differently in apoE4 and apoE3 mice and
      were significantly enriched in NF-kappaB response elements. Direct measurement of
      NF-kappaB-regulated genes revealed that their extent of activation was greater in
      the apoE4 mice. Immunohistochemistry experiments revealed that microglial and NF
      kappaB activation were more pronounced in apoE4 than in apoE3 mice. These
      findings suggest that the increased brain inflammation in apoE4 mice is related
      to disregulation of NF-kappaB signaling pathway.

PMID- 15979313
TI  - Reducing properties, energy efficiency and carbohydrate metabolism in hyperhydric
      and normal carnation shoots cultured in vitro: a hypoxia stress?
AB  - Hyperhydricity is considered as a physiological disorder that can be induced by
      different stressing conditions. In the present work we have studied the metabolic
      and energetic states of hyperhydric carnation shoots. We have evaluated the
      hypothesis that hypoxia stress is the main factor affecting the metabolism of
      hyperhydric leaves. Our results indicate a low level of ATP in hyperhydric
      tissues, but only slight modifications in pyridine nucleotide contents.
      Concurrently, the glucose-6-phosphate dehydrogenase (G-6-PDH; EC 1.1.1.49)
      activity in hyperhydric leaves was increased but glucokinase (GK; EC 2.7.1.2)
      activity was unchanged. We have observed that the metabolism of pyruvate was
      altered in hyperhydric tissues by the induction of pyruvate synthesis via NADP
      dependent malic enzyme (EC 1.1.1.40). The enzymes of the fermentative metabolism
      pyruvate decarboxylase (PDC; EC 4.1.1.1) and alcohol dehydrogenase (ADH; EC
      1.1.1.1) were highly increased in hyperhydric leaves. Sucrose metabolism was
      modified in hyperhydric leaves with a high increase in the activity of both
      synthesis and catabolic enzymes. The analysis of the sucrose, glucose and
      fructose contents indicated that all of these sugars were accumulated in
      hyperhydric leaves. However, the pinitol content was drastically decreased in
      hyperhydric leaves. We consider that these results suggest that hyperhydric
      leaves of carnation have adapted to hypoxia stress conditions by the induction of
      the oxidative pentose phosphate and fermentative pathways.

PMID- 15979314
TI  - Developmental expression of stress response genes in Theobroma cacao leaves and
      their response to Nep1 treatment and a compatible infection by Phytophthora
      megakarya.
AB  - Developmental expression of stress response genes in Theobroma cacao leaves and
      their response to Nep1 and a compatible infection by Phytophthora megakarya were
      studied. Ten genes were selected to represent genes involved in defense (TcCaf-1,
      TcGlu1,3, TcChiB, TcCou-1, and TcPer-1), gene regulation (TcWRKY-1 and TcORFX-1),
      cell wall development (TcCou-1, TcPer-1, and TcGlu-1), or energy production
      (TcLhca-1 and TcrbcS). Leaf development was separated into unexpanded (UE), young
      red (YR), immature green (IG), and mature green (MG). Our data indicates that the
      constitutive defense mechanisms used by cacao leaves differ between different
      developmental stages. TcWRKY-1 and TcChiB were highly expressed in MG leaves, and
      TcPer-1, TcGlu-1, and TcCou-1 were highly expressed in YR leaves. TcGlu1,3 was
      highly expressed in UE and YR leaves, TcCaf-1 was highly expressed in UE leaves,
      and TcLhca-1 and TcrbcS were highly expressed in IG and MG leaves. NEP1 encodes
      the necrosis inducing protein Nep1 produced by Fusarium oxysporum and has
      orthologs in Phytophthora species. Nep1 caused cellular necrosis on MG leaves and
      young pods within 24 h of application. Necrosis was observed on YR leaves 10 days
      after treatment. Expression of TcWRKY-1, TcORFX-1, TcPer-1, and TcGlu-1 was
      enhanced and TcLhca-1 and TcrbcS were repressed in MG leaves after Nep1
      treatment. Expression of TcWRKY-1 and TcORFX-1 was enhanced in YR leaves after
      Nep1 treatment. Infection of MG leaf disks by P. megakarya zoospores enhanced
      expression of TcGlu-1, TcWRKY-1, and TcPer-1 and repressed expression of TcChiB,
      TcLhca-1 and TcrbcS. Five of the six genes that were responsive to Nep1 were
      responsive to infection by P. megakarya. Susceptibility of T. cacao to P.
      megakarya includes altered plant gene expression and phytotoxic molecules like
      Nep1 may contribute to susceptibility.

PMID- 15979315
TI  - Identification and quantification of hypericin and pseudohypericin in different
      Hypericum perforatum L. in vitro cultures.
AB  - Investigations have been made to develop an efficient protocol for
      micropropagation allowing to improve hypericin and pseudohypericin productions in
      Hypericum perforatum L. in vitro cultures. The role of growth regulator
      treatments has been particularly studied. Three in vitro culture lines with
      different morphological characteristics were obtained during H. perforatum
      micropropagation and referred to shoots, calli and plantlets according to their
      appearance. Multiplication and callogenesis from apical segments from sterile
      germinated seedlings were obtained on solid MS/B5 culture medium in the presence
      of N6-benzyladenine (BA) (0.1-5.0 mg/l BA). Regenerative potential of shoots was
      assessed on medium supplemented with auxins (0.05-1.0 mg/l), indole-3-acetic acid
      (IAA) or indole-3-butyric acid (IBA). The main goal of the research was to
      summarize the influence of plant growth regulators on hypericin and
      pseudohypericin productions in in vitro cultures of Hypericum. A rapid method for
      naphtodianthrone quantification was developed. The use of a reversed-phase high
      performance liquid chromatography (HPLC) method with fluorescence detection was
      used. Identification of the compounds was confirmed by electrospray ionization
      mass spectrometry (ESI-MS) with electrospray in negative ion mode [M-H] . Calli,
      shoots and plantlets of H. perforatum produced hypericin and pseudohypericin. The
      concentration range of BA from 0.1 to 2.0 mg/l improved the production of
      hypericin (25-50 microg/g dry mass (DM)) and pseudohypericin (170-350 microg/g
      DM) in shoots. In callus cultures, BA (4.0-5.0 mg/l) did not changed hypericin
      contents (15-20 microg/g DM) but influenced pseudohypericin productions (120-180
      microg/g DM). In the presence of auxins (IAA and IBA), Hypericum plantlets
      produced hypericin (30-100 microg/g DM) and pseudohypericin (120-400 microg/g
      DM). The presence of IAA did not influence naphtodianthrone productions in
      plantlets, but IBA decreased hypericin and pseudohypericin amounts in plantlets.
      The specific accumulation of the naphtodianthrones in in vitro cultures was
      influenced by phytohormonal supplementation of the medium. Results indicated that
      the production of hypericin and pseudohypericin could be increased by carefully
      adapted in vitro cultures. Hypericum in vitro cultures represent promising
      systems for hypericin and pseudohypericin productions.

PMID- 15979316
TI  - Peripheral osteoma of the mandible: case report and review of the literature.
AB  - BACKGROUND: Osteoma is a benign often asymptomatic neoplasm, consisting of well
      differentiated mature bone. This paper reports a case of peripheral osteoma
      located in the anterior mandibular region and provides a review of the literature
      about this lesion in the jaws. PATIENT AND METHODS: A 43-year-old white woman
      presented with a swelling in the left mandible of 7 years duration. The English
      literature was reviewed over the past 76 years and data about location,
      histopathology and number of the peripheral osteomas, sex, and age of the
      patients were evaluated. RESULTS: Data analysis showed 69 well-documented cases
      of peripheral osteoma. Peripheral osteomas are more frequent in the mandible than
      the maxilla and the cancellous type was most frequent; males and females are
      equally affected in the mandible; the age range was 9-85 years. CONCLUSION: The
      peripheral type of osteoma is most common in the lower jaws, occurs at the
      surface of the cortical bone and is sessile or pedicled.

PMID- 15979317
TI  - Immunohistochemical study of vascular endothelial growth factor (VEGF) and bone
      morphogenetic protein-2, -4 (BMP-2, -4) on lengthened rat femurs.
AB  - BACKGROUND: With a hypothesis that "angiogenesis occurs before osteogenesis," an
      experimental study using a rat model was carried out. Histological and
      immunohistochemical examinations of vascular endothelial growth factor (VEGF) and
      bone morphogenetic protein-2, -4 (BMP-2, -4) were performed at the margins of
      bone formation after femoral bone lengthening. MATERIAL AND METHODS: Thirty-five
      Wistar rats weighing 380-400 g (11-week-old males) were used. An external fixator
      was applied on the femur, and an osteotomy performed under general anaesthesia.
      Five days after the operation, femoral lengthening was initiated at a rate of 0.8
      mm/day for 8 days. The rats were sacrificed just after distraction was completed,
      and at 1, 3, 5, 7, 9 and 14 days after distraction. The specimens from these rats
      were stained with haematoxylin-eosin, VEGF, and BMP-2, -4 immunohistochemical
      staining, and were investigated. RESULTS: Expression of VEGF was observed in the
      woven bone at the osteogenetic front and near to osteoblasts around the newly
      formed bone. On the other hand, expressions of BMP-2, -4 were seen in the
      hypertrophic chondrocytes. In the same specimen, the VEGF area was further away
      from the bone stump than the BMP-2, -4 areas. CONCLUSION: These results confirm
      the hypothesis that angiogenesis is induced before osteogenesis.

PMID- 15979318
TI  - Vertebral erosion and paraplegia due to expanding thoracic aneurysm.

PMID- 15979319
TI  - Mitral valve repair for commissural prolapse: surgical techniques and long term
      results.
AB  - OBJECTIVE: The aim of this study was to describe the pattern of lesions
      responsible for commissural prolapse, the techniques of valve repair and their
      long-term results. METHODS: Between 1992 and 2004, 128 mitral valve repairs were
      consecutively performed for commissural prolapse. There were 86 males and 42
      females, the median age was 57.5 years (range 14-84 years). Forty-six percent of
      patients were in NYHA III or IV, mean ejection fraction was 61+/-9.4%. The
      diagnosis of commissural prolapse was recognized by preoperative echocardiography
      in 32% of the patients and was revealed by intraoperative inspection of the valve
      in the other cases. The site of the prolapse was the posteriomedial commissure
      (n=94), the anterior commissure (n=30) or both (n=4). The aetiologies were:
      infective endocarditis (n=56), degenerative (n=46), ischemic (n=25), congenital
      mitral regurgitation (n=1). The commissural prolapse was associated with another
      mitral valvular lesion requiring a specific treatment in 61 cases (47.7%). An
      associated procedure was carried out in 45 patients. RESULTS: The operative
      treatment of the commissural prolapse included: commissural closure 65 (50.8%),
      leaflet resection 31 (24.2%), transposition or shortening of chordae 19 (14.8%),
      reimplantation or shortening of papillary muscles 3 (2.3%), and replacement of
      the commissural area by a partial mitral homograft 10 (8%). In-hospital mortality
      included three deaths (2.3%) and four patients (3.1%) were reoperated: three
      pericardial drainages for hemopericardium and one for mediastinitis. During the
      follow-up, one patient died (0.8%) from myocardial infarction and eight patients
      (6.3%) were reoperated including six (4.7%) for recurrent mitral regurgitation.
      After a median follow-up time of 76.9 months (range from 15 days to 160 months),
      116 patients (90.1%) were in NYHA I. Echocardiographs showed no or minimal
      insufficiency in 112 patients (87.5%) and mild or moderate insufficiency in 10
      patients (7.8%). CONCLUSIONS: The diagnosis of commissural prolapse is difficult
      by preoperative echocardiography. The aetiology of the mitral disease is variable
      (endocarditis, degenerative or ischemic mitral regurgitation). Using a variety of
      techniques, commissural prolapse can be repaired with excellent clinical and
      echographic long-term results.

PMID- 15979320
TI  - Post-transplant lymphoproliferative disorders (PTLD) after solid organ
      transplantation.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a well-recognised and
      potentially fatal complication after solid organ transplantation. They include a
      spectrum of disorders ranging from benign hyperplasia to invasive malignant
      lymphoma. The majority of cases are associated with Epstein Barr virus (EBV)
      driven tumour formation in B cells and are a consequence of the detrimental
      effect of immunosuppressive agents on the immune-control of EBV. This review
      provides an update on the pathogenesis and clinical features of PTLD after solid
      organ transplantation and discusses recent progress in management. Reduction in
      immunosuppressive therapy remains a key component of therapy for EBV-positive
      PTLD and may lead to remission in early disease. Chemotherapy is used when
      reduced immunosuppression fails to control early disease and as initial therapy
      for many cases of late disease. Unfortunately, the mortality for PTLD that fails
      to respond to a reduction in immunosuppression remains high. Newer treatments
      include manipulation of the cytokine environment, B lymphocyte depleting
      antibodies and adoptive T cell immunotherapy using allogeneic or autologous EBV
      specific cytotoxic T lymphocytes. Although early results appear promising, well
      designed clinical trials are needed to assess the efficacy of these novel
      approaches. EBV vaccination may in the future prove an effective prophylaxis
      against EBV-driven PTLD but until then, avoiding excessive immunosuppressive
      therapy may help minimise the risk of PTLD.

PMID- 15979321
TI  - Management of patients with higher risk myelodysplastic syndromes.
AB  - Higher risk myelodysplastic syndromes (MDS) include patients in the Intermediate
      2 and high-risk categories of the International Prognostic Scoring System, as
      well as patients with MDS secondary to radiation or chemical exposure. Ideally,
      the goal of therapy is to alter the natural history of disease in these patients
      to achieve cure or durable remission. High-intensity chemotherapy can achieve
      moderate rates of complete remission, however, durability of remission and
      overall survival tend to be short. Hematopoietic stem cell transplantation (HSCT)
      offers the possibility of cure, with long-term disease-free survival inversely
      related to age. Patients who are elderly or have poor functional status are
      candidates for reduced intensity HSCT, although this is still an experimental
      modality. Azacitidine is a hypomethylating agent that is a reasonable option for
      many patients ineligible for high-intensity therapies. Other therapies, such as
      immunomodulatory agents, arsenic trioxide, and farnesyl transferase inhibitors
      have thus far shown limited usefulness in higher risk MDS. This paper reviews the
      various therapeutic options for higher risk MDS, providing rationale for specific
      management approaches for these patients.

PMID- 15979323
TI  - The risk of lymphoma in the treatment of inflammatory bowel disease with
      immunosuppressive agents.
AB  - Immunosuppressive agents have become an established part of the therapeutic
      armamentarium for inflammatory bowel disease (IBD). However, when used in
      transplant recipients or for other indications, agents that suppress or modulate
      the immune system (immunomodulators) have been associated with an increased risk
      of lymphoma. Fortunately, in part because of the lower doses used in IBD
      patients, the risk of lymphoma in IBD patients appears to be significantly less
      than that associated with renal and hepatic transplant-related immunosuppression.
      Whether the risk of azathioprine or 6-mercaptopurine associated lymphoma in IBD
      is real or relates to the underlying disease remains unclear. The results of
      several recent large well designed population-based studies suggest that the
      lymphoma risk associated with azathioprine and 6-mercaptopurine therapy is likely
      to be of minimal clinical significance compared to the established and more
      frequent risks of myelosuppression and infection, and is far outweighed by the
      clinical benefit of immunomodulator therapy in IBD. While the issue of lymphoma
      risk is likely to become more relevant with the growing number of biologic and
      immunomodulators being tested in clinical trials for IBD, early post-marketing
      surveillance data on infliximab suggests that the lymphoma risk may not be any
      greater than that associated with azathioprine and 6-mercaptopurine.

PMID- 15979322
TI  - Incidence of cancer after immunosuppressive treatment for heart transplantation.
AB  - Prolonged or intensive immunosuppressive therapy used after organ transplantation
      is complicated by an increased incidence of cancer. Striking differences in
      incidence are observed in heart and heart-lung transplant recipients when
      compared with renal transplant patients. The most significant increase was in the
      incidence of lymphomas in cardiac versus renal patients. Moreover, a two-fold
      greater increase of all neoplasms was found in cardiac recipients, with nearly a
      six-fold increase in visceral tumors. Several factors may account for these
      differences. In cardiac allograft recipients, intensive immunosuppression is
      frequently used to reverse acute rejection and the highest number of cardiac
      transplants was performed in the era of polypharmacy, usually consisting of
      triple therapy.

PMID- 15979324
TI  - Immunosuppressive agents are also carcinogens.

PMID- 15979325
TI  - Secondary malignancies after hematopoietic stem cell transplantation.
AB  - Advances in the field of hematopoietic stem cell transplantation have led to an
      increasing number of cures of malignant and non-malignant diseases with this
      therapeutic approach. Long-term survivorship may, however, be associated with
      secondary malignancies, the result of a complex interaction of treatment-,
      recipient- and immunosuppression-related factors. Furthermore, the increasing use
      of donors other than human leukocyte antigen-identical siblings is associated
      with more intense immunosuppression, delayed immune recovery and higher incidence
      of B-cell post-transplantation lymphoproliferative disorders. Here, we review the
      incidence and the risk factors associated with these complications of
      hematopoietic stem cell transplants.

PMID- 15979326
TI  - Ion-ion and ion-molecule reactions at the surface of proteins produced by
      nanospray. Information on the number of acidic residues and control of the number
      of ionized acidic and basic residues.
AB  - Mass Spectra of charge states of folded proteins were obtained with nanospray and
      aqueous solution containing 20 microM the protein (ubiquitin, cytochrome c,
      lysozyme) and one of the NaA salts NaCl, NaI, NaAc (acetate) (1-10 mM). At very
      low collision activated decomposition (CAD), the mass spectra of a protein with
      charge z exhibited a replacement of zH+ with zNa+ and also multiple adducts of
      NaA. Higher CAD converts the NaA adduct peaks to Na minus H peaks. These must be
      due to loss of HA where the H was provided by the protein. The degree of HA loss
      with increasing CAD followed the order I < Cl < Ac. Significantly, the intensity
      of the ions with n (Na minus H) adducts showed a downward break past an n(MAX)
      which is equal to the number of acidic residues of the protein plus the charge of
      the protein. All the observations could be rationalized within the framework of
      the electrospray mechanism and the charge residue model, which predict that due
      to extensive evaporation of solvent, the solutes will reach very high
      concentrations in the final charged droplets. At such high concentrations,
      positive ions such as Na+, NH4+ form ion pairs with ionized acidic residues and
      the negative A- form ion pairs with ionized basic residues of the protein.
      Adducts of Na+, and NaA to backbone amide groups occur also. This reaction
      mechanism fits all the experimental observations and provides predictions that
      the number of acidic and basic groups at the surface of the gaseous protein that
      remain ionized can be controlled by the absence or presence of additives to the
      solution.

PMID- 15979327
TI  - Quantitative analysis of the low molecular weight serum proteome using 18O stable
      isotope labeling in a lung tumor xenograft mouse model.
AB  - With advancements in the analytical technologies and methodologies in proteomics,
      there is great interest in biomarker discovery in biofluids such as serum and
      plasma. Current hypotheses suggest that the low molecular weight (LMW) serum
      proteome possesses an archive of clipped and cleaved protein fragments that may
      provide insight into disease development. Though these biofluids represent
      attractive samples from which new and more accurate disease biomarkers may be
      found, the intrinsic person-to-person variability in these samples complicates
      their discovery. Mice are one of the most extensively used animal models for
      studying human disease because they represent a highly controllable experimental
      model system. In this study, the LMW serum proteome was compared between
      xenografted tumor-bearing mice and control mice by differential labeling
      utilizing trypsin-mediated incorporation of the stable isotope of oxygen, 18O.
      The digestates were combined, fractionated by strong cation exchange
      chromatography, and analyzed by nanoflow reversed-phase liquid chromatography
      coupled online with tandem mass spectrometry, resulting in the identification of
      6003 proteins identified by at least a single, fully tryptic peptide. Almost 1650
      proteins were identified and quantitated by two or more fully tryptic peptides.
      The methodology adopted in this work provides the means for future quantitative
      measurements in comparative animal models of disease and in human disease
      cohorts.

PMID- 15979330
TI  - Pathways of peptide ion fragmentation induced by vacuum ultraviolet light.
AB  - One Hundred Fifty-Seven nm photodissociation of singly protonated peptides
      generates unusual distributions of fragment ions. When the charge is localized at
      the C-terminus of the peptide, spectra are dominated by x-, v-, and w-type
      fragments. When it is sequestered at the N-terminus, a- and d-type ions are
      overwhelmingly abundant. Evidence is presented suggesting that the fragmentation
      occurs via photolytic radical cleavage of the peptide backbone at the bond
      between the alpha- and carbonyl-carbons followed by radical elimination to form
      the observed daughter ions.

PMID- 15979332
TI  - MS2Grouper: group assessment and synthetic replacement of duplicate proteomic
      tandem mass spectra.
AB  - Shotgun proteomics experiments require the collection of thousands of tandem mass
      spectra; these sets of data will continue to grow as new instruments become
      available that can scan at even higher rates. Such data contain substantial
      amounts of redundancy with spectra from a particular peptide being acquired many
      times during a single LC-MS/MS experiment. In this article, we present
      MS2Grouper, an algorithm that detects spectral duplication, assesses groups of
      related spectra, and replaces these groups with synthetic representative spectra.
      Errors in detecting spectral similarity are corrected using a paraclique
      criterion-spectra are only assessed as groups if they are part of a clique of at
      least three completely interrelated spectra or are subsequently added to such
      cliques by being similar to all but one of the clique members. A greedy algorithm
      constructs a representative spectrum for each group by iteratively removing the
      tallest peaks from the spectral collection and matching to peaks in the other
      spectra. This strategy is shown to be effective in reducing spectral counts by up
      to 20% in LC-MS/MS datasets from protein standard mixtures and proteomes,
      reducing database search times without a concomitant reduction in identified
      peptides.

PMID- 15979333
TI  - The utility of accurate mass and LC elution time information in the analysis of
      complex proteomes.
AB  - The combination of mass and normalized elution time (NET) of a peptide identified
      by liquid chromatography-mass spectrometry (LC-MS) measurements can serve as a
      unique signature for that peptide. However, the specificity of an LC-MS
      measurement depends upon the complexity of the proteome (i.e., the number of
      possible peptides) and the accuracy of the LC-MS measurements. In this work,
      theoretical tryptic digests of all predicted proteins from the genomes of three
      organisms of varying complexity were evaluated for specificity. Accuracy of the
      LC-MS measurement of mass-NET pairs (on a 0 to 1.0 NET scale) was described by
      bivariate normal sampling distributions centered on the peptide signatures.
      Measurement accuracy (i.e., mass and NET standard deviations of +/-0.1, 1, 5, and
      10 ppm, and +/-0.01 and 0.05, respectively) was varied to evaluate improvements
      in process quality. The spatially localized confidence score, a conditional
      probability of peptide uniqueness, formed the basis for the peptide
      identification. Application of this approach to organisms with comparatively
      small proteomes, such as Deinococcus radiodurans, shows that modest mass and
      elution time accuracies are generally adequate for confidently identifying most
      peptides. For more complex proteomes, more accurate measurements are required.
      However, the study suggests that the majority of proteins for even the human
      proteome should be identifiable with reasonable confidence by using LC-MS
      measurements with mass accuracies within +/-1 ppm and high efficiency separations
      having elution time measurements within +/-0.01 NET.

PMID- 15979336
TI  - Intriguing mass spectrometric behavior of guanosine under low energy collision
      induced dissociation: H2O adduct formation and gas-phase reactions in the
      collision cell.
AB  - An in-depth study of the fragmentation pathway of guanosine was conducted by
      using an in-source collision-induced dissociation high-mass accuracy tandem mass
      spectrometry experiment. The equivalent of MS4 data, a level of information
      normally achieved on ion trap instruments, was obtained on a Q-TOF mass
      spectrometer. The combination of the features of high-resolution, accuracy, and
      in-source CID permitted the unambiguous elucidation of the different
      fragmentation pathways. Furthermore the elemental compositions of the product
      ions generated were assigned and their mutual genealogical relationships
      established. Formerly proposed dissociation pathways of guanosine were revisited
      and elaborated on more deeply. Furthermore, the presence of H2O in the collision
      cell of several tandem MS instruments was demonstrated and its effect on the
      product ion spectra investigated. The neutral gain of H2O by particular fragments
      of guanosine was experimentally proven by using argon, saturated with H2(18)O, as
      the collision gas. Data indicating the occurrence of more complex reactions in
      the collision cell as a result of the presence of H2O were produced, specifically
      relating to neutral gain/neutral loss sequences. In silico calculations supported
      the experimental observation of neutral gain by guanosine fragments and predicted
      a similar behavior for adenosine. The latter was subsequently experimentally
      confirmed.

PMID- 15979337
TI  - Electrospray ionization mass spectrometry studies of noncovalent myosin VI
      complexes reveal a new specific calmodulin binding site.
AB  - Among the myosin superfamily, myosin VI differs from all others by a reverse
      directionality and a particular motility. Little structural information is
      available for myosin VI. It is known that it binds one calmodulin (CaM) by means
      of a single "IQ motif" and that myosin VI contains a specific insert located at
      the junction between the motor domain (MD) and the lever arm, likely to play a
      critical role for the unusual motility previously observed. Electrospray
      ionization mass spectrometry (MS) was used to determine the CaM and Ca2+
      stoichiometries in several myosin VI constructs. In particular, the experimental
      conditions required for the observation of multiprotein/Ca2+ noncovalent
      assemblies are detailed for two truncated MD constructs (less than 20 kDa) and
      for three full MD constructs (more than 90 KDa). The specificity of the detected
      stoichiometries is discussed for each construct and the resolving power of Time
      of Flight mass spectrometry is stressed, in particular for the detection of metal
      ions binding to high molecular weight complexes. MS reveals a new CaM binding
      site for myosin VI and highlights a different behavior for the five myosin VI
      constructs versus Ca2+ binding. In addition to these stoichiometry based
      experiments, gas-phase dissociation analyses on intact complexes are described.
      They reveal that Ca2+ transfer between protein partners occurs during the
      dissociation process for one construct with a full MD. Charge-transfer and
      dissociation behavior has allowed to draw structural assumptions for the
      interaction of the MD with the CaM N-terminal lobe.

PMID- 15979338
TI  - Multidimensional protein identification technology (MudPIT): technical overview
      of a profiling method optimized for the comprehensive proteomic investigation of
      normal and diseased heart tissue.
AB  - An optimized analytical expression profiling strategy based on gel-free
      multidimensional protein identification technology (MudPIT) is reported for the
      systematic investigation of biochemical (mal)-adaptations associated with healthy
      and diseased heart tissue. Enhanced shotgun proteomic detection coverage and
      improved biological inference is achieved by pre-fractionation of excised mouse
      cardiac muscle into subcellular components, with each organellar fraction
      investigated exhaustively using multiple repeat MudPIT analyses. Functional
      enrichment, high-confidence identification, and relative quantification of
      hundreds of organelle- and tissue-specific proteins are achieved readily,
      including detection of low abundance transcriptional regulators, signaling
      factors, and proteins linked to cardiac disease. Important technical issues
      relating to data validation, including minimization of artifacts stemming from
      biased under-sampling and spurious false discovery, together with suggestions for
      further fine-tuning of sample preparation, are discussed. A framework for follow
      up bioinformatic examination, pattern recognition, and data mining is also
      presented in the context of a stringent application of MudPIT for probing
      fundamental aspects of heart muscle physiology as well as the discovery of
      perturbations associated with heart failure.

PMID- 15979340
TI  - The screening of expression and purification conditions for replicative DNA
      polymerase associated B-subunits, assignment of the exonuclease activity to the C
      terminus of archaeal pol D DP1 subunit.
AB  - The B-subunits of replicative DNA polymerases belong to the superfamily of
      calcineurin-like phosphoesterases and are conserved from Archaea to humans.
      Recently we and others have shown that the B-subunit (DP1) of the archaeal family
      D DNA polymerase is responsible for proofreading 3'-5' exonuclease activity. The
      similarity of B-subunit sequences implies a common fold, but since the key
      catalytic and metal binding residues of the phosphoesterase domain are disrupted
      in the eukaryotic B-subunits, their common function has not been identified. To
      study the structure and activities of B-subunits in more detail, we expressed 13
      different recombinant B-subunits in Escherichia coli. We found that the
      solubility of a protein could be predicted from the calculated GRAVY score. These
      scores were useful for the selection of proteins for successful expression. We
      optimized the expression and purification of Methanocaldococcus (Methanococcus)
      jannaschii DP1 of DNA polymerase D (MjaDP1) and show that the protein co-purifies
      with a thermostable nuclease activity. Truncation of the protein indicates that
      the N-terminus (aa 1-134) is not needed for catalysis. The C-terminal part of the
      protein containing both the calcineurin-like phosphoesterase domain and the OB
      fold is sufficient for the nuclease activity.

PMID- 15979341
TI  - Using voxel-based morphometry to map the structural changes associated with rapid
      conversion in MCI: a longitudinal MRI study.
AB  - Capturing the dynamics of gray matter (GM) atrophy in relation to the conversion
      from mild cognitive impairment (MCI) to clinically probable Alzheimer's disease
      (AD) would be of considerable interest. In this prospective study we have used a
      novel longitudinal voxel-based method to map the progression of GM loss in MCI
      patients over time and compared converters to non-converters. Eighteen amnestic
      MCI patients were followed-up for a predefined fixed period of 18 months and
      conversion was judged according to NINCDS-ADRDA criteria for probable AD. Each
      patient underwent a high-resolution T1-weighted volume MRI scan both at entry in
      the study and 18 months later. We used an optimal VBM protocol to compare
      baseline imaging data of converters to those of non-converters. Moreover, to map
      GM loss from baseline to follow-up assessment, we used a modified voxel-based
      morphometry (VBM) procedure specially designed for longitudinal studies. At the
      end of the follow-up period, seven patients had converted to probable AD. Areas
      of lower baseline GM value in converters mainly included the hippocampus,
      parahippocampal cortex, and lingual and fusiform gyri. Regions of significant GM
      loss over the 18-month follow-up period common to both converters and non
      converters included the temporal neocortex, parahippocampal cortex, orbitofrontal
      and inferior parietal areas, and the left thalamus. However, there was
      significantly greater GM loss in converters relative to non-converters in the
      hippocampal area, inferior and middle temporal gyrus, posterior cingulate, and
      precuneus. This accelerated atrophy may result from both neurofibrillary tangles
      accumulation and parallel pathological processes such as functional alteration in
      the posterior cingulate. The ability to longitudinally assess GM changes in MCI
      offers new perspectives to better understand the pathological processes
      underlying AD and to monitor the effects of treatment on brain structure.

PMID- 15979342
TI  - Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the
      human brain.
AB  - High b value diffusion-weighted images sampled at high angular resolution were
      analyzed using a composite hindered and restricted model of diffusion (CHARMED).
      Measurements and simulations of diffusion in white matter using CHARMED provide
      an unbiased estimate of fiber orientation with consistently smaller angular
      uncertainty than when calculated using a DTI model or with a dual tensor model
      for any given signal-to-noise level. Images based on the population fraction of
      the restricted compartment provide a new contrast mechanism that enhances white
      matter like DTI. Nevertheless, it is assumed that these images might be more
      sensitive than DTI to white matter disorders. We also provide here an
      experimental design and analysis framework to implement CHARMED MRI that is
      feasible on human clinical scanners.

PMID- 15979343
TI  - Cerebral correlates of delta waves during non-REM sleep revisited.
AB  - We aimed at characterizing the neural correlates of delta activity during Non
      Rapid Eye Movement (NREM) sleep in non-sleep-deprived normal young adults, based
      on the statistical analysis of a positron emission tomography (PET) sleep data
      set. One hundred fifteen PET scans were obtained using H(2)(15)O under continuous
      polygraphic monitoring during stages 2-4 of NREM sleep. Correlations between
      regional cerebral blood flow (rCBF) and delta power (1.5-4 Hz) spectral density
      were analyzed using statistical parametric mapping (SPM2). Delta power values
      obtained at central scalp locations negatively correlated during NREM sleep with
      rCBF in the ventromedial prefrontal cortex, the basal forebrain, the striatum,
      the anterior insula, and the precuneus. These regions embrace the set of brain
      areas in which rCBF decreases during slow wave sleep (SWS) as compared to Rapid
      Eye Movement (REM) sleep and wakefulness (Maquet, P., Degueldre, C., Delfiore,
      G., Aerts, J., Peters, J.M., Luxen, A., Franck, G., 1997. Functional neuroanatomy
      of human slow wave sleep. J. Neurosci. 17, 2807-S2812), supporting the notion
      that delta activity is a valuable prominent feature of NREM sleep. A strong
      association was observed between rCBF in the ventromedial prefrontal regions and
      delta power, in agreement with electrophysiological studies. In contrast to the
      results of a previous PET study investigating the brain correlates of delta
      activity (Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A.C.,
      Jones, B.E., 1997. Regional cerebral blood flow changes as a function of delta
      and spindle activity during slow wave sleep in humans. J. Neurosci. 17, 4800
      4808), in which waking scans were mixed with NREM sleep scans, no correlation was
      found with thalamus activity. This latter result stresses the importance of an
      extra-thalamic delta rhythm among the synchronous NREM sleep oscillations.
      Consequently, this rCBF distribution might preferentially reflect a particular
      modulation of the cellular processes involved in the generation of cortical delta
      waves during NREM sleep.

PMID- 15979344
TI  - A parietal-frontal network studied by somatosensory oddball MEG responses, and
      its cross-modal consistency.
AB  - Previous studies using functional magnetic resonance imaging (fMRI) and event
      related potentials (ERPs) of the brain have found that a distributed parietal
      frontal neuronal network is activated in normals during both auditory and visual
      oddball tasks. The common cortical regions in this network are inferior parietal
      lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and
      dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network
      is activated by oddball tasks during somatosensory stimulation. The present study
      addressed this question by testing healthy adults as they performed a novel
      median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An
      automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal
      (MSST) algorithm, localized multiple neuronal generators, and identified their
      time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median
      nerve oddball responses, with IPL/SMG activation significantly preceding ACC and
      DLPFC activation. Thus, the same parietal-frontal neuronal network that shows
      activation during auditory and visual oddball tests is activated in a median
      nerve oddball paradigm. Regions uniquely related to somatosensory oddball
      responses (e.g., primary and secondary somatosensory, dorsal premotor, primary
      motor, and supplementary motor areas) were also localized. Since the parietal
      frontal network supports attentional allocation during performance of the task,
      this study may provide a novel method, as well as normative baseline data, for
      examining attention-related deficits in the somatosensory system of patients with
      neurological or psychiatric disorders.

PMID- 15979345
TI  - A positron emission tomography (PET) investigation of the role of striatal
      dopamine (D2) receptor availability in spatial cognition.
AB  - The functional significance of age-related changes in regional brain dopamine
      (DA) function is poorly understood in health. Two recent studies have reported
      positive linear associations between measures of striatal DA (D2) receptor
      availability (binding potential) and specific aspects of motor and cognitive
      performance, after controlling for the effects of age [(Volkow, N.D., Gur, R.C.,
      Wang, G.-J., Fowler, J.S., Moberg, P.J., Ding, Y.-S., Hitzemann, R., Smith, G.,
      Logan, J., 1998. Association between decline in brain dopamine activity with age
      and cognitive and motor impairment in healthy individuals. Am. J. Psychiatry 155
      (3), 344-349; Backman, L., Ginovart, N., Dixon, R.A., Wahlin, T.-B.R., Wahlin,
      A., Halldin, C., Farde, L., 2000. Age-related cognitive deficits mediated by
      changes in the striatal dopamine system. Am. J. Psychiatry 157 (4), 635-637)]. We
      investigated the relationship between measures of striatal DA (D2) receptor
      availability and visuo-spatial cognitive performance in thirty healthy post
      menopausal women aged 58-90 years. [(11)C] Raclopride (RAC) positron emission
      tomography (PET) was used to assess dopamine (D2) receptor availability. The
      CANTAB neuropsychological test battery was used to assess spatial span, spatial
      working memory (SWM) and planning ability. Age showed significant linear
      correlations with several of the CANTAB performance measures. After controlling
      for age effects, DA (D2) receptor measures in left-sided striatal regions
      (caudate and putamen) were significantly and positively correlated with 'perfect
      solution' scores--the measure of performance accuracy--on the Tower of London
      (TOL) test of spatial planning. When this relationship was examined in relation
      to task difficulty, only perfect scores for the most 'difficult' (4-move)
      problems were significantly correlated with BP measures in all striatal regions,
      most notably the right and left caudate nuclei. Paradoxically, individuals with
      higher DA (D2) receptor measures in the right caudate performed less accurately
      on the SWM task, exhibiting a higher number of errors within each search
      sequence. The relative contribution of striatal DA (D2) receptor availability to
      specific aspects of cognitive performance needs to be evaluated in larger mixed
      sex samples to facilitate the meaningful investigation of the potential
      therapeutic benefits of DA (D2) agonists in later life.

PMID- 15979346
TI  - Spatial registration of multichannel multi-subject fNIRS data to MNI space
      without MRI.
AB  - The registration of functional brain data to the common brain space offers great
      advantages for inter-modal data integration and sharing. However, this is
      difficult to achieve in functional near-infrared spectroscopy (fNIRS) because
      fNIRS data are primary obtained from the head surface and lack structural
      information of the measured brain. Therefore, in our previous articles, we
      presented a method for probabilistic registration of fNIRS data to the standard
      Montreal Neurological Institute (MNI) template through international 10-20 system
      without using the subject's magnetic resonance image (MRI). In the current study,
      we demonstrate our method with a new statistical model to facilitate group
      studies and provide information on different components of variability. We adopt
      an analysis similar to the single-factor one-way classification analysis of
      variance based on random effects model to examine the variability involved in our
      improvised method of probabilistic registration of fNIRS data. We tested this
      method by registering head surface data of twelve subjects to seventeen reference
      MRI data sets and found that the standard deviation in probabilistic registration
      thus performed for given head surface points is approximately within the range of
      4.7 to 7.0 mm. This means that, if the spatial registration error is within an
      acceptable tolerance limit, it is possible to perform multi-subject fNIRS
      analysis to make inference at the population level and to provide information on
      positional variability in the population, even when subjects' MRIs are not
      available. In essence, the current method enables the multi-subject fNIRS data to
      be presented in the MNI space with clear description of associated positional
      variability. Such data presentation on a common platform, will not only
      strengthen the validity of the population analysis of fNIRS studies, but will
      also facilitate both intra- and inter-modal data sharing among the neuroimaging
      community.

PMID- 15979347
TI  - Molecular phylogeny and stripe pattern evolution in the cardinalfish genus
      Apogon.
AB  - Cardinalfishes of the genus Apogon (Apogonidae) are one of the most speciose
      (>200 species) and numerically dominant fishes in coral reefs. Although the genus
      is divided into 10 subgenera, more than 70% of the species are included in the
      subgenus Ostorhinchus, most having either horizontal or vertical lines on the
      body. The phylogenetic relationship among 32 species of subgenus Ostorhinchus and
      11 species of four other subgenera of Apogon, based on mitochondrially encoded
      12S and 16S ribosomal genes and intervening tRNA(Val) gene, were investigated,
      using two species of the apogonid genus Fowleria as outgroups. The analyses
      demonstrated that Ostorhinchus (the most speciose subgenus) was polyphyletic,
      comprising at least three lineages, Ostorhinchus I, II, and III. Ostorhinchus I
      included two species, A. (O.) amboinensis and A. (O.) sangiensis, being a sister
      group to subgenus Zoramia. Ostorhinchus II and III included species with
      horizontal and vertical lines on the body, respectively. The respective
      monophylies of the latter two groups, together with a molecular clock
      calibration, indicated that in the evolutionary history of the genus, basic
      stripe patterns evolved first (more than 20 million years BP), with subsequent
      pattern diversification and modification.

PMID- 15979348
TI  - A novel simultaneous modeling approach to estimate linearity of pharmacokinetic
      parameters, including saturation of intestinal efflux, in the rat.
AB  - INTRODUCTION: Various independent methods exist for the estimation of linearity
      of pharmacokinetic parameters in vivo. A novel simultaneous modeling approach has
      been developed in the rat that in combination allows estimation of the rate and
      extent of duodenal absorption, hepatic first pass extraction and saturation of
      potential dose-dependent duodenal bioavailability (saturation of intestinal
      efflux). METHODS: Simultaneous modeling of plasma concentrations of a Pfizer
      compound in the rat were conducted using NONMEM after (1) accelerated
      intravenous, intraduodenal, and intraportal infusions over 5 h and (2) 5-min
      intravenous infusions of 0.28 and 1.4 mg doses. RESULTS: The data was best
      described by a two-compartment linear pharmacokinetic model with good agreement
      between observed and model predicted plasma concentrations following the various
      routes of administration. Clearance was estimated to be linear up to plasma
      concentrations of 1200 ng/ml. The estimated rate constants (+/-asymptotic errors)
      for intraduodenal absorption (KA), movement of drug from plasma to tissue (K23)
      and movement of drug from tissue to plasma (K32) were 0.645+/-0.107, 18.0+/-2.98,
      and 2.02+/-0.209 h(-1), respectively. The rate constants for drug elimination
      from the central compartment (K20) after 5-min intravenous infusion or
      accelerated infusion were 3.24+/-0.6 or 6.26+/-1.64 h(-1). The estimated maximal
      extent of first pass extraction was 17%. The model (including increasing duodenal
      bioavailability as the amount in the duodenum increases, from a minimum of 5% to
      a maximum estimated intraportal bioavailability value-83%) indicated a saturable
      intestinal efflux process. DISCUSSION: This novel study design and the proposed
      method for data analysis provides a robust and efficient means for assessing the
      linearity of multiple pharmacokinetic processes while accounting for the multi
      compartmental distribution characteristics of the test compound.

PMID- 15979349
TI  - Non-drug-related electrocardiographic features in animal models in safety
      pharmacology.
AB  - No study of a test article is complete without attempting to determine its risk
      for production of toxicity to all important components of cardiovascular function
      (e.g., electrophysiological, mechanical, biochemical, baroreceptor).
      Electrocardiography is extremely useful for interrogating important
      electrophysiological properties: chronotropy (heart rate), dromotropy (conduction
      through the atria and ventricles, and through atrioventricular conduction), and
      predilection to produce arrhythmia, in particular, torsade de pointes. However,
      there are many factors that make electrocardiography less than optimal for
      detecting potential toxicological effects in studies of safety pharmacology. This
      paper will present examples of common difficulties in recording or in
      interpreting electrocardiograms, specifically due to artifacts in ECGs produced
      by the methods of electrocardiography, and by the "unusual" electrophysiology of
      the species/subject. One of the most contentious issues in electrocardiology is
      correction of QT for heart rate (Mark, M. (2001) Problems of heart rate
      correction in assessment of drug-induced QT interval prolongation. Journal of
      Cardiovascular Electrophysiology, 12, 411-420). This will not be discussed.

PMID- 15979350
TI  - Articular chondrocyte passage number: influence on adhesion, migration,
      cytoskeletal organisation and phenotype in response to nano- and micro-metric
      topography.
AB  - The isolation and culture of articular chondrocytes is a prerequisite of their
      use in tissue engineering, but prolonged culture and passaging is associated with
      de-differentiation. In this paper we studied the influence of nanometric and
      micrometric grooves (85 nm to 8 microm in depth and 2 microm to 20 microm in
      width) on 1st and 2nd passage ovine chondrocytes since our earlier findings
      indicate that primary cells are not affected by such features. 1st and 2nd
      passage chondrocytes cultured on grooved substrata showed a polarisation of cell
      shape parallel to the groove long axis and F-actin condensations were evident at
      groove ridge boundaries. An increase in cell migration with increasing groove
      depth was observed. Both passages of chondrocytes maintained type II collagen
      expression, but to a lesser degree in 2nd. This study demonstrates that passage
      number alters the response of chondrocytes to micrometric and nanometric
      topography, and could be important in ex vivo cartilage engineering.

PMID- 15979351
TI  - Circadian changes in uterine artery and ovarian stromal blood flow after
      pituitary down-regulation.
AB  - OBJECTIVE: To investigate changes in the uterine artery and ovarian stromal blood
      flow in relation to the time of the day after pituitary down-regulation during in
      vitro fertilization treatment. METHODS: Thirteen women were recruited. The
      uterine artery blood flow was studied using pulsed color Doppler ultrasonography
      and the ovarian stromal blood flow was measured using three-dimensional power
      Doppler ultrasonography. Ultrasound scan examinations and blood pressure
      measurements were performed in the morning and evening. RESULTS: The diastolic
      and the mean arterial pressures were significantly higher in the evening. An
      increase in the uterine artery pulsatility index and resistance index in the
      evening was observed. The ovarian vascularization index, vascularization flow
      index, and right ovarian flow index were significantly lower in the evening.
      CONCLUSIONS: Despite the small sample size, we have demonstrated the presence of
      a diurnal change in uterine artery and ovarian stromal blood flow after pituitary
      down-regulation. Such changes may be related to the systemic change in the
      sympathetic system and hence vascular resistance. Future study regarding ovarian
      stromal blood flow should take into account the effect of the time of the day on
      the readings in order to avoid misleading interpretation of data.

PMID- 15979352
TI  - Large-conductance Ca2+-dependent K+ channels regulate basal uteroplacental blood
      flow in ovine pregnancy.
AB  - OBJECTIVES: The mechanisms regulating basal uteroplacental blood flow (UBF) and
      the greater than 30-fold increase observed in normal pregnancy remain unclear.
      Although vascular growth contributes in early gestation, vasodilation accounts
      for the exponential rise seen in the last third of pregnancy. Large conductance
      potassium channels (BK(Ca)) are expressed in uterine vascular smooth muscle
      (VSM), but the extent of their role in regulating UBF in pregnancy is unclear.
      Therefore, we determined if BK(Ca) regulate basal UBF during ovine pregnancy.
      METHODS: Studies were performed at 113 to 127 days and 135 to 150 days of
      gestation in eight pregnant ewes instrumented with uterine artery flow probes and
      uterine arterial and venous catheters. Tetraethylammonium chloride (TEA), a
      BK(Ca)-specific inhibitor at less than 1.0 mM, was infused intra-arterially into
      the pregnant uterine horn over 60 minutes to achieve levels of 0.001-0.35 mM
      while continuously monitoring UBF, arterial pressure (MAP), and heart rate (HR).
      Uterine arterial and venous blood was collected simultaneously to measure uterine
      cyclic guanosine monophosphate (cGMP) synthesis. RESULTS: Intra-arterial TEA dose
      dependently decreased basal UBF in the early (R = 0.81, n = 36, P <.001) and late
      (R = 0.72, n = 31, P <.001) study periods without altering contralateral UBF,
      MAP, and HR. The IC(50) was 0.2 mM and basal UBF decreased >or=80% at 0.35 mM in
      both periods. Although UBF fell greater than 40% at estimated plasma TEA levels
      of 0.3 mM, uterine arterial cGMP was unchanged, uterine venous cGMP rose, and
      uterine cGMP synthesis was unchanged; therefore, upstream events associated with
      BK(Ca) activation were unaffected by blockade. CONCLUSIONS: These are the first
      data demonstrating that BK(Ca) are essential in the maintenance of basal UBF in
      the last third of ovine pregnancy.

PMID- 15979353
TI  - Developmental changes in adrenocorticotrophin (ACTH)-induced expression of ACTH
      receptor and steroid acute regulatory protein mRNA in ovine fetal adrenal cells.
AB  - OBJECTIVES: Adrenocorticotrophin (ACTH) plays an important role in mediating the
      increase in cortisol output in the late gestation sheep fetus. At the adrenal
      itself, heightened expression of ACTH receptor (ACTH-R) and steroid acute
      regulatory protein (StAR) appear to be important parallel changes. This study
      examined how ACTH affects ACTH-R and StAR mRNA expression, and cortisol
      production in adrenocortical cells isolated from fetuses of varying gestational
      age (dGA). We hypothesized that the ability of ACTH to stimulate its receptor and
      StAR mRNA expression would be greater close to term than earlier in development.
      METHODS: Adrenals were obtained from fetuses (100-105, 120, or 135-139 dGA), and
      the cortical cells were dispersed. After 3 days of culture, cells were stimulated
      with ACTH(1-24), and the cells and medium were collected at different time points
      (0, 3, 6, 9, 12, and 24 hours) for measurement of cortisol and ACTH-R and StAR
      mRNA. RESULTS: Cortisol secretion was increased after ACTH treatment in all three
      age cohorts. Cells from the 135-139 dGA group secreted the most cortisol,
      followed by the 100-105 and then the 120 dGA groups (P <.05). ACTH-R mRNA levels
      before and after ACTH were higher in the late compared to both earlier groups.
      StAR mRNA levels before and after ACTH were higher in the 100-105 and 135 than in
      the 120 dGA group. The time to peak ACTH-R mRNA response was age-dependent, with
      the 100-105 dGA cells taking longer to attain maximum levels. Maximal StAR mRNA
      levels were not age-related. CONCLUSION: The data suggest that ACTH-R and StAR
      are indeed key mediators of fetal adrenocortical responsiveness, and that ACTH is
      able to up-regulate responsiveness, and hence cortisol production, by increasing
      their expression.

PMID- 15979355
TI  - Adiponectin concentrations in maternal serum: elevated in preeclampsia but
      unrelated to insulin sensitivity.
AB  - OBJECTIVE: Adiponectin is an adipocyte-derived protein with profound insulin
      sensitizing, anti-inflammatory, and antiatherogenic effects. Surprisingly, recent
      evidence suggests that adiponectin concentrations are increased during
      preeclampsia, which is characterized by insulin resistance. We studied whether
      serum adiponectin is related to insulin sensitivity in preeclamptic and
      normotensive pregnant women. METHODS: We measured serum adiponectin
      concentrations and insulin sensitivity (intravenous glucose tolerance
      test/minimal model) in 22 women with preeclampsia and 15 normotensive controls
      with similar pre-pregnancy body mass index (BMI) (range 18-29 kg/m(2)) between 29
      and 39 weeks of gestation. Fourteen cases and 10 controls were also studied 6-22
      weeks after delivery. No subject had gestational diabetes. RESULTS: During
      pregnancy, the mean adiponectin concentration in preeclamptic women was 10.3 (SD
      4.2) mug/mL as compared to 7.9 (SD 2.9) microg/mL in normotensive controls (95%
      confidence interval [CI] for difference 0.1-5.3 microg/mL; P = .04). Adiponectin
      concentrations were unrelated to insulin sensitivity both in preeclamptic and
      normotensive subjects; insulin sensitivity was decreased in preeclampsia (P =
      .01). After delivery, mean adiponectin concentration was lower than during
      pregnancy: 7.4 (SD 3.0) microg/mL in preeclamptic subjects (P = .001) and 7.1 (SD
      1.6) microg/mL in normotensive controls (P = .06) and similar in cases and
      controls (95% CI for difference -1.7-2.3 microg/mL, P = .7). CONCLUSIONS: Despite
      their reduced insulin sensitivity, preeclamptic women have higher adiponectin
      concentrations than normotensive pregnant women. These concentrations are
      unrelated to insulin sensitivity. After pregnancy, the difference in adiponectin
      concentrations is no longer present between the two groups. These findings are
      consistent with a role of adiponectin in the pathophysiology of preeclampsia.

PMID- 15979354
TI  - Expression of steroid receptor coactivators in cultured cells from paired
      myometrial and fibroid tissues.
AB  - OBJECTIVES: Fibroid tumor growth in the myometrium appears to be regulated by
      estrogens but the role of estrogen receptor (ER) coregulators, such as the
      steroid receptor coactivator (SRC) family members, in fibroid growth is currently
      unknown. The aims of this study were to compare the expression of the SRC-1, SRC
      2, and SRC-3 coactivators between fibroids and normal myometrium in pure
      populations of cultured smooth muscle cells (SMC) and microvascular endothelial
      cells (MEC), and also between both cell types, and to identify any relationship
      between the SRC expression profiles and the known ER status of the SMC and MEC
      samples examined in this study. METHODS: Reverse transcriptase-polymerase chain
      reaction (RT-PCR) coupled with Southern blot analysis was used to derive a
      semiquantitative estimate of the relative levels of SRC-1, SRC-2, and SRC-3
      expression in pure populations of SMC (>98% alpha-smooth muscle actin [SMA](+))
      and MEC (>99% CD31(+)) isolated and cultured from eight samples of paired human
      myometrial and fibroid tissue. RESULTS: The mean levels of SRC-1, SRC-2, and SRC
      3 were each similar in normal myometrium compared to fibroids for SMC and also
      for MEC. However, SRC-1, SRC-2, and SRC-3 levels were each significantly higher
      in SMC compared to MEC from both myometrial and fibroid samples, although for SRC
      3 there was a trend for higher levels in myometrial samples that did not reach
      significance. While all SMC samples expressed ERalpha and high coactivator
      levels, there does not appear to be a relationship between coactivator expression
      levels and the presence or absence of ERalpha in MEC samples. CONCLUSION:
      Coactivators may be more important in ERalpha-mediated growth of SMC than for
      MEC. Although the SRC family members are likely to play a role in the response of
      fibroid SMC to estrogen, via ERalpha, changes in their levels do not appear to
      contribute to the increased sensitivity of fibroid SMC to estrogen.

PMID- 15979356
TI  - Hypocretins (orexins): clinical impact of the discovery of a neurotransmitter.
AB  - Hypothalamic excitatory hypocretin (orexin) neurons have been discovered in 1998
      and found to have widespread projections to basal forebrain, monoaminergic and
      cholinergic brainstem, and spinal cord regions. The hypocretin system is
      influenced both neuronally (e.g. suprachiasmatic nucleus, GABAergic, cholinergic
      and aminergic brainstem nuclei) as well as metabolically (e.g. glucose, ghrelin,
      and leptin). Physiologically the hypocretin system has been implicated in the
      regulation of behaviours that are associated with wakefulness, locomotion, and
      feeding. A role in REM sleep, neuroendocrine, autonomic and metabolic functions
      has also been suggested. Pathophysiologically a deficient hypocretin
      neurotransmission has been found in human narcolepsy and (engineered) animal
      models of the disorder. Different mechanisms are involved including (1)
      degeneration of hypocretin neurons (mice), (2) hypocretin ligand deficiency
      (humans, mice, dogs), (3) hypocretin receptor deficiency (mice, dogs). Reports of
      low hypocretin-1 cerebrospinal fluid levels in neurologic conditions (e.g.
      Guillain-Barre syndrome, traumatic brain injury, hypothalamic lesions) with and
      without sleep-wake disturbances and, on the other hand, observations of normal
      levels in about 11% of narcoleptics raise questions about the exact nature and
      pathophysiological base of the link between hypocretin deficiency and clinical
      manifestations in human narcolepsy.

PMID- 15979357
TI  - Partial nicotinic receptor blockade unmasks a modulatory role of nitric oxide on
      urethral striated neuromuscular transmission.
AB  - The objective of this study was to investigate the possible modulatory role of
      endogenous nitric oxide (NO) production on the urethral striated muscle (USM)
      function in the sheep urethra. Significant NO synthase (NOS) activity was
      measured in both the particulate and cytosolic fractions of USM homogenates. NOS
      activity was calcium-dependent and showed greater inhibition by NOS inhibitors
      selective of the neural NOS isoform (nNOS). nNOS immunoreactivity was present in
      intramural nerves as well as in the sarcolemma of some striated fibers, being
      denser at the neuromuscular junction (NMJ). Double immunolabeling showed co
      localization of nNOS with both alpha-bungarotoxin and choline acetyltransferase,
      at the USM endplates. For the first time, functional data support a role of NO on
      the USM contractility "in vitro," which became evident following partial
      nicotinic receptor inactivation with low concentrations of D-tubocurarine. Only
      under D-tubocurarine (0.25 microM) treatment, different NOS inhibitors, specially
      N(G)-propyl-L-arginine, as well as the guanylate cyclase inhibitor ODQ, all
      showed a significant enhancing effect on contractions induced by electrical field
      stimulation of intrinsic somatic nerves. These data suggest that local production
      of NO at the urethral NMJ may modulate release and/or action of acetylcholine on
      motor endplates by cyclic GMP-mediated effects. This modulatory action could be
      especially relevant when neuromuscular transmission at the USM is impaired.

PMID- 15979358
TI  - Acute demyelinating encephalomyelitis (ADEM), cryptococcal reactivation and
      disseminated Herpes simplex in an HIV infected child following HAART.
AB  - Highly active antiretroviral treatment (HAART) is increasingly becoming available
      for HIV infected children in South Africa. We describe a 7-year-old HIV infected
      child (CD4=10, viral load =180,669copies/ml) who develops a cryptococcal
      meningitis, with raised intracranial pressure, complicated by ADEM and
      disseminated Herpes simplex infection following commencement of HAART.

PMID- 15979359
TI  - Genetic influence on the clinical characteristics and outcome of febrile seizures
      -a retrospective study.
AB  - PURPOSE: To assess the influence of the family history (FH) of epilepsy or
      febrile seizures (FSs) on the clinical presentation of FSs and on their outcome.
      METHODS: We reviewed the charts of 482 children admitted to the Ste-Justine
      Hospital with FSs between 3 months and 6 years of age and followed for at least 5
      years. RESULTS: Children with a positive FH of epilepsy (n=67) showed
      significantly more focal and recurrent FSs than those without such a FH. The risk
      of developing partial epilepsy (n=17) or generalized epilepsy (n=19) was
      significantly greater in children with focal or recurrent FSs, respectively. In
      children with focal FSs, only two out of 30 (6.7%) children with a negative FH of
      epilepsy developed partial epilepsy compared with four out of nine (44.4%)
      children with a positive FH. In children with recurrent FSs, as much as seven out
      of 34 (20.6%) children with a positive FH of epilepsy developed generalized
      epilepsy compared to only eight out of 161 (0.05%) of those with a negative FH.
      Nevertheless, when not taking into account the clinical presentation of FSs, the
      positive FH of epilepsy constituted a risk factor for developing generalized but
      not partial epilepsy. Finally, children with a positive FH of FSs (n=120)
      exhibited significantly more recurrent FSs than those without such a FH, but this
      did not modify the risk of epilepsy. CONCLUSION: The FH of FSs and/or epilepsy
      should be taken into account when evaluating the risk of FSs recurrence and of
      epilepsy.

PMID- 15979360
TI  - Treatment of peripheral neuropathic pain: a simulation model.
AB  - OBJECTIVE: To describe the use of a generalizable stochastic-simulation model of
      the treatment of neuropathic pain associated with peripheral neuropathies.
      METHODS: We developed a model to simulate treatment outcomes in a hypothetical
      cohort of patients with peripheral neuropathies. Each patient was randomly
      assigned an average pretreatment daily pain score (on a 0-10 scale), based on an
      assumed distribution of mean pretreatment pain scores in the cohort. Patients
      were randomly assigned daily pain scores, based on their pretreatment average and
      an assumed distribution of daily pain scores around this mean. Treatment outcomes
      were then simulated using the expected mean change (vs. baseline) in pain scores.
      Model outcomes include the expected increase in days with no or mild pain (score
      < or = 3), days with > or = 30% and > or = 50% reductions in pain intensity, and
      days with 2- and 3-point absolute reductions in pain intensity. To illustrate its
      use, the model was estimated over a 12-week period using data from a recent
      clinical trial of a new antiepileptic (pregabalin). RESULTS: Treatment over 12
      weeks (84 days) was projected to result in 26 (+/-0.4) (mean [+/-SE]) additional
      (vs. no treatment) days with no or mild pain, 33 (+/-0.5) days with a > or = 30%
      reduction in pain intensity, 28 (+/-0.4) days with > or = 50% reduction in pain
      intensity, and 34 (+/-0.5) and 30 (+/-0.5) days with > or = 2-point and > or = 3
      point absolute reductions in pain intensity. CONCLUSIONS: When combined with data
      on health-state utilities and treatment costs, this new analytical tool can
      provide a foundation for formal cost-effectiveness evaluations of interventions
      for painful peripheral neuropathies.

PMID- 15979361
TI  - A novel high temperature 1H NMR imaging probe for combustion studies: the
      behaviour of both a lit and unlit methane gas jet.
AB  - The design of a NMR probe suitable for very high temperature samples is
      described. The loop gap resonator is water cooled and tuned to 100 MHz for use in
      a 2.4 T horizontal bore magnet. The probe has been specifically designed for
      imaging of the combustion process. An experiment is described in this paper which
      shows the behaviour of a methane gas jet when both lit and unlit. The jet of gas
      may be observed in its unlit state flowing at up to 2 ms(-1) from a 1 mm diameter
      orifice using a Single Point Imaging technique. Images of the lit gas show loss
      of nuclear polarisation within 3 mm of the orifice. A residual amount of un
      decomposed gas is visible in the first few millimetres of the flame neck. A
      computational fluid dynamics model is used to verify the distribution of
      molecular methane, as well as the temperature of the flame.

PMID- 15979362
TI  - On-resonance low B1 pulses for imaging of the effects of PARACEST agents.
AB  - Application of the exchange-sensitive, low-power RF pulses positioned on the bulk
      water resonance for imaging of the effects of PARACEST agents is proposed as an
      alternative to the standard CW off-resonance irradiation. Specifically, we
      applied a low-power WALTZ-16 RF train, with the 90 degrees pulse unit replaced by
      a pulse of the fixed length (WALTZ-16*). Using this sequence, the bulk water
      signal was found to be sensitive to exchange lifetimes with PARACEST complex
      bound protons, the transverse relaxation time of bulk water, and longitudinal
      relaxation time of bound protons. In this report, the concept of using WALTZ-16*
      to "activate" a PARACEST effect is introduced and some of the salient features of
      this technique with respect to experimental conditions and performance levels are
      discussed. Computational predictions are verified and explored by comparison with
      experimental spectroscopic and imaging data. It is shown that WALTZ-16* can be
      used to detect PARACEST agents with an RF intensity as low as 200 Hz for
      concentrations as low as a few tens of microM for lanthanide chelates having
      appropriate water-exchange rates (Tm,Dy).

PMID- 15979363
TI  - Tackling the EGFR in pathological tissue remodelling.
AB  - Tissue remodelling is an adaptive physiological event initiated by physical
      and/or hormonal stimuli and characterised by extracellular matrix modifications,
      inflammation, cellular hypertrophy, proliferation and/or apoptosis. Although its
      initial effects may be beneficial for the maintenance of organ function, it is
      evident that sustained remodelling processes can lead to pathological outcomes,
      such as fibrosis in asthma, and cardiac hypertrophy in heart failure. Our
      research is focussed upon cardiac hypertrophy and the significant contribution of
      the molecular pathway, termed 'the triple membrane-passing signalling' paradigm
      (TMPS), to this phenomenon. Cardiac hypertrophy describes the enlargement, but
      not proliferation, of cardiomyocytes in response to mechanical or hormonal
      factors to normalise cardiac output and accompanies other features of cardiac
      remodelling. As a major independent risk factor for heart failure, it is
      imperative that the molecular mechanisms that govern this phenotype are
      determined to identify possible therapeutic targets. This review will focus on
      the importance of matrix metalloproteases and epidermal growth factor receptors
      in the TMPS pathway and their potential as pharmacological targets for heart
      failure therapy. The evidence provided may have implications for pathological
      tissue remodelling in other organs.

PMID- 15979364
TI  - Role of nitric oxide in larval and juvenile fish.
AB  - Fish are known to express the three isoforms of nitric oxide synthase (NOS), the
      constitutive forms endothelial or eNOS, neuronal or nNOS and the inducible form
      iNOS. Most studies in fish have focussed on possible roles for NO in
      cardiovascular physiology although there has been recent attention on the role of
      nNOS in embryonic development. However compared to mammalian studies there have
      been relatively few studies on effects of nitric oxide (NO) on fish. Studies on
      heart and blood vessel preparations from various fish species appear to show
      results specific to the species or to the particular preparation. Possible roles
      of NO in the in vivo biology of adult fish or larval fish have received little
      attention. This article reviews effects of nitric oxide on cardiovascular
      physiology in fish with special emphasis on larval fish. It introduces some
      experimental work on possible signaling pathways in larval fish and introduces
      the possibility that NO could be an important environmental influence for some
      aquatic organisms. In higher vertebrates LPS (lipopolysaccharide) is known to
      activate the cytokine signaling system and stimulate increased expression of iNOS
      and increased production of NO, but this remains less investigated in fish. The
      effects of LPS on cardiovascular and osmoregulatory physiology of larval and
      juvenile salmonids are discussed and a possible role of NO in stress-induced
      drinking is suggested.

PMID- 15979365
TI  - Nitric oxide in marine invertebrates: a comparative perspective.
AB  - Since the discovery of the biological effects of nitric oxide (NO) more than two
      decades ago, NO has been identified as an important physiological modulator and a
      messenger molecule in mammals. Parallel to these studies, evidence that has
      accumulated in recent years has revealed that the NO signalling pathway is spread
      throughout the entire phylogenetic scale, being increasingly found in lower
      organisms, ranging from Chordata to Mollusca. The present review attempts to
      provide a survey of current knowledge of the genesis and possible roles of NO and
      the related signalling pathway in marine invertebrates, with special emphasis on
      Sepia, a choice dictated by the increasing appreciation of cephalopods as most
      valuable model systems for studies of NO biology and the present expectation for
      new exciting insights into as yet little explored segments of NO biology.

PMID- 15979366
TI  - ICV CRF and isolation stress differentially enhance plasma corticosterone
      concentrations in layer- and meat-type neonatal chicks.
AB  - The present study compared the plasma corticosterone concentrations between meat-
      and layer-type neonatal chicks (Gallus gallus) (1) exposed to isolation-induced
      stress or (2) injected intracerebroventricularly (ICV) with corticotropin
      releasing factor (CRF). Both types of neonatal chicks housed in groups were
      individually introduced to an open field arena and locomotion and distress
      induced vocalizations were monitored for 10 min. The responses of the two strains
      were remarkably different, with meat-type chicks being less active than layer
      type chicks. Distress-induced vocalizations were drastically decreased over time
      in meat-type chicks while they remained high in layer-type chicks throughout the
      test. Plasma corticosterone concentrations measured at the end of the test were
      significantly higher in layer-type chicks than in meat-type ones. Plasma
      corticosterone concentrations measured 10 min after the ICV injection of CRF were
      significantly higher in layer- than meat-type chicks. These results indicate that
      meat-type chicks have either a greater capability to acclimatize to novel
      environments, or a blunted HPA axis compared with layer-type chicks.

PMID- 15979367
TI  - Adenosine/nitric oxide crosstalk in the branchial circulation of Squalus
      acanthias and Anguilla anguilla.
AB  - The potent vasomodulator adenosine (AD), thanks to the interaction with by A(1)
      and A(2) receptors, dilates systemic, coronary and cerebral vasculatures but
      exert a constrictor action in several vessels of respiratory organs. Recent
      investigations suggest that nitric oxide (NO) contributes to AD effects. In fish,
      both NO and AD induce atypical effects compared to mammals. Since there is very
      little information on the role of NO and its involvement in mediating the actions
      of AD in fish, we have analysed this question in the branchial vasculature of the
      elasmobranch Squalus acanthias and the teleost Anguilla anguilla using an
      isolated perfused head and a branchial basket preparation, respectively. In both
      dogfish and eel, AD dose-response curves showed a biphasic effect:
      vasoconstriction (pico to nanomolar range) and vasodilation (micromolar range).
      Both effects were abolished by the classic xanthine inhibitor theophylline (Theo)
      and also by specific antagonists of A(1) and A(2) receptor subtypes. To analyse
      the involvement of the NO/cGMP system in the AD responses, we tested a NOS
      inhibitor, l-NIO, and a specific soluble guanylate cyclase (sGC) blocker, ODQ. In
      both dogfish and eel preparations l-NIO abrogated all vasomotor effects of AD,
      whereas ODQ blocked the AD-mediated vasoconstriction without affecting the
      vasorelaxant response. This indicates that only AD-induced vasoconstriction is
      mediated by a NO-cGMP-dependent mechanism. By using the NO donor SIN-1, we showed
      a dose-dependent vasoconstrictory effect which was completely blocked by ODQ.
      These results provide compelling evidence that the vasoactive role of AD in the
      branchial circulation of S. acanthias and A. anguilla involves a NO signalling.

PMID- 15979368
TI  - Role of nitric oxide in the control of coronary resistance in teleosts.
AB  - In mammals, the in vivo coronary blood flow and myocardial oxygen consumption are
      closely related via changes in coronary resistance in response to the metabolic
      demands of the myocardium. A fine neurohumoral regulation of coronary resistance
      holds true also in fish, and particularly in teleosts, where several
      vasoconstrictive and vasodilative mechanisms have been described, with numerous
      putative effectors, including prostanoids, acetylcholine, adrenaline, serotonin,
      adenosine, steroid hormones. Here, a resume is reported of the available evidence
      on the involvement of nitric oxide (NO) in the control of coronary resistance in
      teleosts and particularly in salmonids. Most of the evidence reported is from a
      comprehensive study performed on a Langedorff-type preparation of the isolated
      trout heart. Using a physio-pharmacological approach, the experiments performed
      on this preparation have demonstrated that trout coronary resistance is reduced
      by l-arginine (NOS substrate), nitroprusside and SNAP (NO donors) and is
      increased by the NOS inhibitors l-NNA and l-NAME. The vasodilation induced by
      nitroprusside is blocked by the guanylate cyclase inhibitor methylene blue. l
      arginine increases NO release in the perfusate, while l-NNA reduces the release.
      NO release is inversely related with the coronary resistance. l-NNA inhibits the
      vasodilatory effects of acetylcholine, serotonin and adenosine. The vasodilation
      induced by adenosine is accompanied by NO release and involves stretch receptors.
      Hypoxia induces vasodilation and both adenosine and NO release in the
      preparation; the NO release under hypoxia is blocked by theophylline. On the
      whole these data indicate that NO plays a central role in the control of coronary
      resistance in trout. In particular, a main role for NO as an amplifier of the
      adenosine-mediated vasodilation under hypoxia can be hypothesized.

PMID- 15979369
TI  - Variations in gastric acid secretion during periods of fasting between two
      species of shark.
AB  - Vertebrates differ in their regulation of gastric acid secretion during periods
      of fasting, yet it is unknown why these differences occur. Elasmobranch fishes
      are the earliest known vertebrates to develop an acid secreting stomach and as
      such may make a good comparative model for determining the causative factors
      behind these differences. We measured gastric pH and temperature continuously
      during periods of fasting in captive free-swimming nurse sharks (Ginglymostoma
      cirratum) using autonomous pH/temperature data-loggers. All nurse sharks secreted
      strong gastric acids (minimum pH 0.4) after feeding; however, for most of the
      sharks, pH increased to 8.2-8.7, 2-3 days after feeding. Half of the sharks also
      exhibited periodic oscillations in pH when the stomach was empty that ranged from
      1.1 to 8.7 (acid secretion ceased for 11.3 +/- 4.3 h day(-1)). This is in
      contrast to the gastric pH changes observed from leopard sharks (Triakis
      semifasciata) in a previous study, where the stomach remains acidic during
      fasting. The leopard shark is a relatively active, more frequently feeding
      predator, and continuous acid secretion may increase digestive efficiency. In
      contrast, the nurse shark is less active and is thought to feed less frequently.
      Periodic cessation of acid secretion may be an energy conserving mechanism used
      by animals that feed infrequently and experience extended periods of fasting.

PMID- 15979370
TI  - AMP-deaminase in elasmobranch fish: a comparative histochemical and enzymatic
      study.
AB  - AMP-deaminase activity was measured in white muscle from a wide range of fish,
      including one cyclostome, 13 chondrosteans, and one teleost to elucidate the
      pattern of the AMP-deaminase activity in white muscle of fish. Compared to a
      mammalian (rat) muscle extract, low enzyme activities are found in the cyclostome
      and two elasmobranchs from two families (Scyliorhinidae, Hexanchidae). In
      contrast, higher AMP-deaminase activities, similar to mammals, are expressed in
      Squalidae, all families of skates, Chimaeridae and in the teleostean fish. We
      then compared AMP-deaminase activities in red and white muscles from two
      representative elasmobranch fish, the dogfish (Scyliorhinus canicula) and the
      thornback ray (Raja clavata). The fibre type composition and distribution of the
      locomotory musculature were determined in these two elasmobranchs to establish a
      relationship between the morphology, the type of fibres of the locomotion
      implicated muscles and the AMP-deaminase activity. Experimental data are
      discussed with respect to the layout of fibres in the myotome. In both species,
      three fibre types were identified. In the two fish myotomes, most of the axial
      muscles are white fibres while red fibres constitute a thin sheet. Some
      differences were observed between the two species in the distribution of
      intermediate fibres: in dogfish, these are located between the red and white
      fibres; in thornback ray, some are dispersed within the white fibre region, while
      others form an intermediary layer like in dogfish. These results suggest that in
      the course of evolution, an amplification of the AMP-deaminase activity in muscle
      was coupled with increase of complexity of the muscular structure.

PMID- 15979371
TI  - Development and application of a brain-specific cDNA microarray for effect
      evaluation of neuro-active pharmaceuticals in zebrafish (Danio rerio).
AB  - The environmental fate and ecotoxicological effect of pharmaceuticals are poorly
      understood, and standardized tests to detect and evaluate their potential effects
      in the environment are not available. We developed a zebrafish brain-specific
      microarray containing 682 neurologically relevant cDNA-fragments. To investigate
      the applicability of this microarray for studying neurotoxic modes-of-action and
      impact assessment of neuro-active pharmaceuticals in zebrafish, chlorpromazine
      was used as a model compound. After exposure to chlorpromazine (75 microg/L) for
      2, 4, 14 and 28 days or control treatment RNA was extracted from brains of males
      and females. Fluorescently labeled cDNA was prepared and hybridized to the custom
      microarray. In total, 56 genes were differentially expressed in brains of male
      and/or female zebrafish, of which most genes were down-regulated. A clear
      difference in response to chlorpromazine exposure between males and females was
      observed with exposure time as well as in functional classes of affected genes.
      The presented study is one of the first reports on molecular effects of human
      neuro-active pharmaceuticals in aquatic non-target organisms. This new genomic
      tool successfully detected gene expression effects of exposure to chlorpromazine
      in the brain of zebrafish. Reported gene expression effects are found to be
      consistent with literature data for other laboratory animals.

PMID- 15979372
TI  - The Caenorhabditis elegans FancD2 ortholog is required for survival following DNA
      damage.
AB  - Fanconi anemia (FA) is an autosomal recessive disease characterized by bone
      marrow failure, congenital abnormalities, and cancer susceptibility. There are 11
      FA complementation groups in human where 8 genes have been identified. We found
      that FancD2 is conserved in evolution and present in the genome of the nematode
      Caenorhabditis elegans. The gene Y41E3.9 (CeFancD2) encodes a structural ortholog
      of human FANCD2 and is composed of 10 predicted exons. Our analysis showed that
      exons 6 and 7 were absent from a CeFancD2 EST suggesting the presence of a splice
      variant. In an attempt to characterize its role in DNA damage, we depleted worms
      of CeFANCD2 using RNAi. When the CeFANCD2(RNAi) worms were treated with a
      crosslinking agent, a significant drop in the progeny survival was noted. These
      worms were also sensitive, although to a lesser extent, to ionizing radiation
      (IR). Therefore, these data support an important role for CeFANCD2 in DNA damage
      response as for its human counterpart. The data also support the usefulness of C.
      elegans to study the Fanconi anemia pathway, and emphasize the biological
      importance of FANCD2 in DNA damage response throughout evolution.

PMID- 15979373
TI  - Intermittent monoarthritis from sarcoidosis.

PMID- 15979374
TI  - Dimerization of chemokine receptors and its functional consequences.
AB  - It became clear over the recent years that most, if not all, G protein-coupled
      receptors (GPCR) are able to form dimers or higher order oligomers. Chemokine
      receptors make no exception to this new rule and both homo- and
      heterodimerization were demonstrated for CC and CXC receptors. Functional
      analyses demonstrated negative binding cooperativity between the two subunits of
      a dimer. The consequence is that only one chemokine can bind with high affinity
      onto a receptor dimer. In the context of receptor activation, this implies that
      the motions of helical domains triggered by the binding of agonists induce
      correlated changes in the other protomer. The impact of the chemokine
      dimerization process in terms of co-receptor function and drug development is
      discussed.

PMID- 15979375
TI  - Medical image registration with partial data.
AB  - We have developed a general-purpose registration algorithm for medical images and
      volumes. The transformation between images is modeled as locally affine but
      globally smooth, and explicitly accounts for local and global variations in image
      intensities. An explicit model of missing data is also incorporated, allowing us
      to simultaneously segment and register images with partial or missing data. The
      algorithm is built upon a differential multiscale framework and incorporates the
      expectation maximization algorithm. We show that this approach is highly
      effective in registering a range of synthetic and clinical medical images.

PMID- 15979377
TI  - Simulation and systematic errors in prediction.

PMID- 15979378
TI  - Focused metabolomic profiling in the drug development process: advances from
      lipid profiling.
AB  - The highly parallel analytical technologies comprising 'omics promised to
      dramatically improve drug development efficiency by increasing knowledge and
      improving decision-making capabilities. On this point, the 'omics have largely
      been a disappointment. The major reason genomics, transcriptomics and proteomics
      fail to improve decision making capabilities is that they produce so many false
      positive results that it is difficult to be sure that findings are valid.
      Metabolomics is not immune to this problem but, when practiced effectively, the
      technology can reliably produce knowledge to aid in decision making. In
      particular, focused metabolomics platforms - those that restrict their target
      analytes to those measured well by the technology - can produce data with
      properties that maximize sensitivity and minimize the false discovery problem.
      The most developed focused metabolomics area is lipid profiling.

PMID- 15979379
TI  - Intrabodies as drug discovery tools and therapeutics.
AB  - Within the biomedical and pharmaceutical communities there is an ongoing need to
      find new technologies that can be used to elucidate disease mechanisms and
      provide novel therapeutics. Antibodies are arguably the most powerful tools in
      biomedical research, and antibodies specific for extracellular or cell-surface
      targets are currently the fastest growing class of new therapeutic molecules.
      However, the majority of potential therapeutic targets are intracellular, and
      antibodies cannot readily be leveraged against such molecules, in the context of
      a viable cell or organism, because of the inability of most antibodies to form
      stable structures in an intracellular environment. Advances in recent years, in
      particular the development of intracellular screening protocols and the
      definition of antibody structures that retain their antigen-binding function in
      an intracellular context, have allowed the robust isolation of a subset of
      antibodies that can function in an intracellular environment. These antibodies,
      generally referred to as intrabodies, have immense potential in the process of
      drug development and may ultimately become therapeutic entities in their own
      right.

PMID- 15979380
TI  - Analysis of amelogenin gene (AMGX, AMGY) expression in ameloblastoma.
AB  - Although the amelogenin gene is expressed in ameloblastoma, the precise
      expression pattern of X and Y amelogenin genes (AMGX, AMGY) in this tumor has not
      yet been identified. In this study, we analyzed amelogenin gene expression in 19
      samples (9 male, 10 female) of oral ameloblastomas by RT-PCR and detect the
      chromosomal origin of amelogenin mRNA by restriction enzyme digestion of the RT
      PCR product. All tumor samples expressed amelogenin mRNA. We could detect
      increased level of AMGY expression in all male samples, higher than that of AMEX.
      It is an interesting finding as in normal male tooth development, the expression
      of AMGY is very much lower than that of AMGX. We postulate that epigenetic change
      of sex chromosomes may have some correlations with tumorigenesis of
      ameloblastoma. We also discuss the other possible mechanisms and points for
      future studies on this change in expression pattern.

PMID- 15979381
TI  - Elective and therapeutic selective neck dissection.
AB  - Selective neck dissection is a modification of the more comprehensive modified
      radical or radical neck dissection that is designed to remove only those nodal
      levels considered to be at risk for harboring nodal metastases. The role of
      selective neck dissection continues to evolve: while initially designed as a
      staging and diagnostic procedure for patients without clinical evidence of nodal
      disease, a growing body of literature suggests that selective neck dissection has
      a therapeutic role in patients with clinical and histologic evidence of nodal
      metastases. The rationale behind selective neck dissection, its application in
      the clinically negative but histologically node-positive neck and the extended
      application of selective neck dissection in patients with clinical evidence of
      nodal disease are discussed.

PMID- 15979382
TI  - Smokeless tobacco (khaini) extracts modulate gene expression in epithelial cell
      culture from an oral hyperplasia.
AB  - Smokeless tobacco (ST) usage is a growing public health problem worldwide.
      Exposure to smokeless tobacco is carcinogenic to humans. The molecular
      mechanism(s) underlying ST associated oral carcinogenesis remain largely unknown.
      The major challenge is to identify the key factor(s) involved in malignant
      transformation of oral lesions. Knowledge of these factors will provide candidate
      diagnostic biomarkers and targets for early intervention. To identify the
      molecular targets in ST associated oral lesions, we established and purified
      cultures of epithelial cells (AMOL-III) from an oral leukoplakia with
      histological evidence of hyperplasia with hyperkeratosis from gingivo-buccal
      sulcus of a smokeless tobacco (khaini) consumer. Cell cultures were characterized
      and modulation of gene expression in response to smokeless tobacco extract (STE)
      was investigated using confocal microscopy and immunoblotting. AMOL-III cells
      showed altered expression of cell cycle regulators namely p53, p21waf1/cip1,
      hdm2, proliferation marker Ki67 and transcription factor Ets-1. These cells did
      not harbor HPV 16/18. No mutation was detected in H-Ras codon 12/13 or in p53
      exons 5-9 in AMOL-III cells. STE treatment of these cells resulted in loss of
      pRb, RARbeta, p21 waf1/cip1 and O6-methyl guanine-DNA methyl transferase (MGMT)
      while the expression of cyclin D1 was increased. To our knowledge this is the
      first report to demonstrate that khaini modulates expression of multiple cellular
      targets including proteins involved in cell cycle regulation and DNA methylation,
      which may lead the oral epithelial cells down the carcinogenic pathway. This in
      vitro model system assumes importance in unraveling the cellular and molecular
      mechanisms implicated in smokeless tobacco associated early oral cancer
      progression.

PMID- 15979383
TI  - Nitric oxide induces oral squamous cell carcinoma cells apoptosis with p53
      accumulation.
AB  - Nitric oxide has been reported to have cytotoxic effects in several tumor cells.
      The objective of this study was to investigate the effects of exogenous nitric
      oxide on apopotosis in oral squamous cell carcinoma cells and to reveal its
      possible mechanism. Tca8113 cells were cultured with various concentrations of
      nitric oxide that were released from sodium nitroprusside (SNP). Nitrite/nitrate
      levels in the culture supernatant were determined using a commercial available
      nitric oxide kit. Cellular proliferation was determined by MTT assay. Apoptosis
      was detected by flow cytometry. Expression of inducible nitric oxide synthase
      (iNOS) was determined by immunocytochemistry. p53 expression was assessed by
      Western blot. SNP can release nitric oxide into the culture medium in a dose
      dependent manner. Nitric oxide remarkably inhibits proliferation in a dose and
      time-dependent manners and lead to apoptosis of the Tca8113 cell. The p53
      expression was elevated accompanying by the increased apoptotic cells. No
      difference of iNOS was found whether or not the cells were treated with SNP.
      Exogenous nitric oxide had an inhibitory effect on Tca8113 cells proliferation in
      a dose and time-dependent manners and possibly via p53 dependent apoptosis
      pathway. Exogenous nitric oxide had no significant effect on cellular iNOS
      protein.

PMID- 15979384
TI  - Effects of IkappaB kinase alpha on the differentiation of squamous carcinoma
      cells.
AB  - IkappaB kinase (IKK) alpha and beta share the function to phosphorylate IkappaB
      to activate a transcription factor NF-kappaB. Recent reports, however, revealed
      differences in the functions of the two kinases. The present study was designed
      to determine a unique function of IKKalpha on the differentiation of squamous
      cell carcinoma (SCC). Transfection with IKKalpha gene, but neither IKKbeta nor NF
      kappaB gene, inhibited the constitutive expressions as well as extracellular
      calcium-induced expressions of involucrin and filaggrin, epithelial
      differentiation markers, in cultured SCC cells. Morphological changes from
      polygonal to fibroblastic shape were seen in the SCC cells stably expressing
      green-fluorescent protein (GFP)-fused IKKalpha while intracellular localization
      of GFP-IKKalpha differed from that of GFP-IKKbeta. Interestingly, phorbol
      myristate acetate together with IKKalpha gene transfection strongly inhibited the
      expression of involucrin in SCC cells and induced the phosphorylation of serine
      residue in IKKalpha, suggesting that protein kinase C is involved in the effect
      of IKKalpha on the differentiation of SCC cells. In conclusion, high expression
      of IKKalpha may serve as an intracellular signal to halt the epithelial
      differentiation of SCC cells.

PMID- 15979385
TI  - Oral cancer: the association between nation-based alcohol-drinking profiles and
      oral cancer mortality.
AB  - The unclear association between different nation-based alcohol-drinking profiles
      and oral cancer mortality was investigated using, as observational units, 20
      countries from Europe, Northern America, Far Eastern Asia, with cross-nationally
      comparable data. Stepwise multiple regression analyses were run with male age
      standardised, mortality rate (ASMR) as explanatory variable and annual adult
      alcohol consumption, adult smoking prevalence, life expectancy, as explanatory.
      Large between-country differences in ASMR (range, 0.88-6.87 per 100,000) were
      found, but the mean value was similar to the global estimate (3.31 vs. 3.09 per
      100,000). Differences in alcohol consumption (2.06-21.03 annual litres per
      capita) and in distribution between beverages were reported. Wine was the most
      prevalent alcoholic beverage in 45% of cases. Significant increases in ASMR for
      every litre of pure ethanol (0.15 per 100,000; 95 CI, 0.01-0.29) and spirits
      (0.26 per 100,000; 95 CI, 0.03-0.49), non-significant effects for beer and wine
      were estimated. The impact of alcohol on oral cancer deaths would be higher than
      expected and the drinking profile could affect cancer mortality, probably because
      of the different drinking pattern of spirit drinkers, usually consuming huge
      alcohol quantities on single occasions, and the different concentrations of
      ethanol and cancer-preventing compounds such as polyphenols, in the various
      beverages.

PMID- 15979386
TI  - The epigenetic control of antigenic variation in Plasmodium falciparum.
AB  - Much of what is known about antigenic variation in the human malaria parasite
      Plasmodium falciparum has been established by the study of phenotypic changes at
      the surface of parasitized red blood cells. Although this has contributed to our
      fundamental understanding of immune escape, nothing conclusive has been
      elucidated about the molecular mechanisms that determine activation and silencing
      of members of the antigenic variation var gene family. Recent findings indicate
      that reversible chromatin modifications and perinuclear gene movement are
      epigenetic factors that define the silent and active states of telomere-adjacent
      var genes.

PMID- 15979387
TI  - The viriosphere, diversity, and genetic exchange within phage communities.
AB  - Natural phage communities are reservoirs of the greatest uncharacterized genetic
      diversity on Earth. Yet, identical phage sequences can be found in extremely
      different environments, which implies that there is wide circulation of viral
      genes among distantly related host populations. Further evidence of genetic
      exchange among phage and host communities is the presence in phage of genes
      coding for proteins that are essential for photosynthesis. These observations
      support the idea that a primary role of host populations in phage ecology and
      evolution is to serve as vectors for genetic exchange.

PMID- 15979388
TI  - Phage abortive infection in lactococci: variations on a theme.
AB  - Abortive infection (Abi) systems, also called phage exclusion, block phage
      multiplication and cause premature bacterial cell death upon phage infection.
      This decreases the number of progeny particles and limits their spread to other
      cells allowing the bacterial population to survive. Twenty Abi systems have been
      isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation
      processes, where phage attacks are of economical importance. Recent insights in
      their expression and mode of action indicate that, behind diverse phenotypic and
      molecular effects, lactococcal Abis share common traits with the well-studied
      Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent
      analysis indicates that Abis might have additional roles other than conferring
      phage resistance.

PMID- 15979389
TI  - Phage regulatory circuits and virulence gene expression.
AB  - In many pathogenic bacteria, genes that encode virulence factors are located in
      the genomes of prophages. Clearly bacteriophages are important vectors for
      disseminating virulence genes, but, in addition, do phage regulatory circuits
      contribute to expression of these genes? Phages of the lambda family that have
      genes encoding Shiga toxin are found in certain pathogenic Escherichia coli
      (known as Shiga toxin producing E. coli) and the filamentous phage CTXphi, that
      carries genes encoding cholera toxin (CTX), is found in Vibrio cholerae. Both the
      lambda and CTXphi phages have repressor systems that maintain their respective
      prophages in a quiescent state, and in both types of prophages this repressed
      state is abolished when the host cell SOS response is activated. In the lambda
      type of prophages, only binding of the phage-encoded repressor is involved in
      repression and this repressor ultimately controls Shiga toxin production and/or
      release. In the CTXphi prophage, binding of LexA, the bacterial regulator of SOS,
      in addition to binding of the repressor is involved in repression; the repressor
      has only limited control over CTX production and has no influence on its release.

PMID- 15979390
TI  - Bacteriophage endolysins--current state of research and applications.
AB  - Endolysins are phage-encoded enzymes that break down bacterial peptidoglycan at
      the terminal stage of the phage reproduction cycle. Their action is tightly
      regulated by holins, by membrane arrest, and by conversion from their inactive to
      active state. Recent research has not only revealed the unexpected diversity of
      these highly specific hydrolases but has also yielded insights into their modular
      organization and their three-dimensional structures. Their N-terminal catalytic
      domains are able to target almost every possible bond in the peptidoglycan
      network, and their corresponding C-terminal cell wall binding domains target the
      enzymes to their substrate. Owing to their specificity and high activity,
      endolysins have been employed for various in vitro and in vivo aims, in food
      science, in microbial diagnostics, and for treatment of experimental infections.
      Clearly, phage endolysins represent great tools for use in molecular biology,
      biotechnology and in medicine, and we are just beginning to tap this potential.

PMID- 15979391
TI  - War is peace--dispatches from the bacterial and phage killing fields.
AB  - Large-scale sequence analyses of phage and bacteria have provided new insights
      into the diverse and multifaceted interactions of these genomes. Such
      interactions are important because they determine the partitioning of a large
      fraction of global biomass. Furthermore, the struggle between phage and bacteria
      has had a significant impact on the evolution of the biosphere. This competition
      for resources has created an enormous pool of genetic diversity. Eons of
      horizontal genetic transfer have permitted the entire biosphere to directly
      benefit from a bargain-basement source of evolutionary innovation.

PMID- 15979392
TI  - Evaluation of the ability of a battery of three in vitro genotoxicity tests to
      discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity
      and relative predictivity.
AB  - The performance of a battery of three of the most commonly used in vitro
      genotoxicity tests--Ames+mouse lymphoma assay (MLA)+in vitro micronucleus (MN) or
      chromosomal aberrations (CA) test--has been evaluated for its ability to
      discriminate rodent carcinogens and non-carcinogens, from a large database of
      over 700 chemicals compiled from the CPDB ("Gold"), NTP, IARC and other
      publications. We re-evaluated many (113 MLA and 30 CA) previously published
      genotoxicity results in order to categorise the performance of these assays using
      the response categories we established. The sensitivity of the three-test battery
      was high. Of the 553 carcinogens for which there were valid genotoxicity data,
      93% of the rodent carcinogens evaluated in at least one assay gave positive
      results in at least one of the three tests. Combinations of two and three test
      systems had greater sensitivity than individual tests resulting in sensitivities
      of around 90% or more, depending on test combination. Only 19 carcinogens (out of
      206 tested in all three tests, considering CA and MN as alternatives) gave
      consistently negative results in a full three-test battery. Most were either
      carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome
      proliferators, hormonal carcinogens) considered not necessarily relevant for
      humans, or were extremely weak (presumed) genotoxic carcinogens (e.g. N
      nitrosodiphenylamine). Two carcinogens (5-chloro-o-toluidine, 1,1,2,2
      tetrachloroethane) may have a genotoxic element to their carcinogenicity and may
      have been expected to produce positive results somewhere in the battery. We
      identified 183 chemicals that were non-carcinogenic after testing in both male
      and female rats and mice. There were genotoxicity data on 177 of these. The
      specificity of the Ames test was reasonable (73.9%), but all mammalian cell tests
      had very low specificity (i.e. below 45%), and this declined to extremely low
      levels in combinations of two and three test systems. When all three tests were
      performed, 75-95% of non-carcinogens gave positive (i.e. false positive) results
      in at least one test in the battery. The extremely low specificity highlights the
      importance of understanding the mechanism by which genotoxicity may be induced
      (whether it is relevant for the whole animal or human) and using weight of
      evidence approaches to assess the carcinogenic risk from a positive genotoxicity
      signal. It also highlights deficiencies in the current prediction from and
      understanding of such in vitro results for the in vivo situation. It may even
      signal the need for either a reassessment of the conditions and criteria for
      positive results (cytotoxicity, solubility, etc.) or the development and use of a
      completely new set of in vitro tests (e.g. mutation in transgenic cell lines,
      systems with inherent metabolic activity avoiding the use of S9, measurement of
      genetic changes in more cancer-relevant genes or hotspots of genes, etc.). It was
      very difficult to assess the performance of the in vitro MN test, particularly in
      combination with other assays, because the published database for this assay is
      relatively small at this time. The specificity values for the in vitro MN assay
      may improve if data from a larger proportion of the known non-carcinogens becomes
      available, and a larger published database of results with the MN assay is
      urgently needed if this test is to be appreciated for regulatory use. However,
      specificity levels of <50% will still be unacceptable. Despite these issues, by
      adopting a relative predictivity (RP) measure (ratio of real:false results), it
      was possible to establish that positive results in all three tests indicate the
      chemical is greater than three times more likely to be a rodent carcinogen than a
      non-carcinogen. Likewise, negative results in all three tests indicate the
      chemical is greater than two times more likely to be a rodent non-carcinogen than
      a carcinogen. This RP measure is considered a useful tool for industry to assess
      the likelihood of a chemical possessing carcinogenic potential from batteries of
      positive or negative results.

PMID- 15979393
TI  - Yb3+ as an origin of the strong anti-Stokes luminescence in NIR FT-Raman spectra
      of some lanthanide sesquioxides.
AB  - Strong anti-Stokes bands observed in FT-Raman spectra of Y2O3, Gd2O3 and Lu2O3
      are explained by NIR luminescence of Yb3+ impurities present in sesquioxides
      after the excitation with the 1064 nm line of an Nd:YAG laser. Samples of
      Y2O3:Yb, Ga2O3:Yb, CeO2:Yb, Gd2O3:Yb and Lu2O3:Yb were prepared by solution
      combustion synthesis procedure using urea. All materials were investigated by FT
      Raman and FT-NIR spectroscopy and characterized by X-ray powder diffraction.

PMID- 15979394
TI  - The vibrational spectrum of the stable free radical 1,1,3,3-tetramethylisoindolin
      2-yloxyl.
AB  - Solid and solution IR and Raman spectra of a stable nitroxide radical, 1,1,3,3
      tetramethylisoindolin-2-yloxyl (TMIO), are reported and compared to ab initio
      density functional theory calculations of the vibrational frequencies to obtain
      unequivocal band assignments, in particular of the NO stretching frequency,
      nu(NO). The band position was found to be at 1431 cm(-1) for the solid, which is
      well outside the previously published range of 1310-1380 cm(-1) for nitroxide
      radicals. This apparently anomalous peak position was confirmed by undertaking
      isotopic substitution studies through the preparation and recording of
      vibrational spectra of tetrakis(trideuteriomethyl)isoindolin-2-yloxyl ([2H12]
      TMIO) and [2H12,15N]-TMIO analogues. Solution spectra of TMIO in methanol and
      CCl4 are assessed for possible solvent-dependent spin density distribution
      effects in the NO bond.

PMID- 15979395
TI  - X-ray diffraction and Raman studies of the CuGeO3(III)-(IV) transformation under
      high pressures.
AB  - Both X-ray diffraction and Raman spectroscopy measurement were carried out on the
      same powder sample of CuGeO(3)(III) in a diamond anvil cell to high pressures at
      room temperature. The phase transformation of (III)-(IV) phase was observed at
      about 7GPa with both methods and the results were also in accord with previous
      powder diffraction and Raman measurements, respectively. However, the powder
      diffraction data were strikingly different from those reported in a recent single
      crystal study on the phase (III). It is, therefore, evident that the phase
      transformations in CuGeO(3)(III) would be as complicated as those in CuGeO(3)(I)
      and that the monoclinic phase obtained from single-crystal phase (III) at
      approximately 7GPa is not the phase (IV) previously observed but rather a new
      phase (IVa) in CuGeO(3).

PMID- 15979396
TI  - Spectral and thermal studies of divalent transition metal complexes with indole-2
      carboxylic acid and 4-substituted hydrazinethiocarbamide.
AB  - Ternary complexes of Co(II), Ni(II) and Cu(II) with indole-2-carboxylic acid (A)
      and 4-substituted hydrazinethiocarbamide (L) [4-phenylhydrazinethiocarbamide
      (L1), 4-benzylhydrazinethiocarbamide (L2) and 4-(2
      propenyl)hydrazinethiocarbamide (L3)] were prepared. The structures of the
      complexes were proposed by molar conductance, electronic, IR, 1H NMR, mass
      spectra as well as thermogravimetric (TG) studies. An octahedral structure is
      suggested for Co(II), Ni(II) and Cu(II) ternary complexes.

PMID- 15979397
TI  - Fluorescence properties of Eu3+ ions doped borate and fluoroborate glasses
      containing lithium, zinc and lead.
AB  - The influence of glass composition on the fluorescence properties of Eu3+ ions
      doped borate and fluoroborate glasses modified with Li+, Zn2+ and Pb2+ cations
      have been investigated. The magnitude of splittings of 7F1 levels are analyzed
      using crystal-field (CF) analysis. The relative intensities of 5D0 --> 7F2 to 5D0
      --> 7F1 transitions, crystal-field strength parameters and decay times of the 5D0
      level have been determined and are found to be lower for Pb based glasses than
      those of Zn/Li based glasses. The lifetimes of 5D0 level are found to increase
      when borate glasses are modified with pure fluorides than with oxides and
      oxyfluorides. The fluorescence decay of 5D0 level fits perfect single exponential
      in the Eu3+:glass systems studied which indicates the absence of energy transfer
      between Eu3+ ions in these glasses.

PMID- 15979398
TI  - Characterization of spectroscopic of Pr(DBM)3(TPPO)2 containing poly(methyl
      methacrylate).
AB  - The absorption and fluorescence spectra of Pr(DBM)3(TPPO)2 (DBM:
      dibenzoylmethane, TPPO: triphenylphosphine oxide) containing poly(methyl
      methacrylate) (PMMA) were measured. The energy levels are assigned and analyzed
      in terms of the free-ion Hamiltonian model. From the data available in the
      absorption spectrum, various spectroscopic parameters such as the spherically
      symmetric part of the free-ion Hamiltonian (E(AVG)), Slater-Condon (F2, F4, F6),
      spin-orbit interaction (zeta), Judd-Ofelt (omega2, omega4, omega6) parameters and
      the reduced matrix elements are derived. The radiative properties of
      Pr(DBM)3(TPPO)2 containing PMMA were also predicted according to the Judd-Ofelt
      theory. The values of the fluorescence branching ratio and the emission cross
      section of 3P0 --> 3F2 fluorescence transition revealed that Pr(DBM)3(TPPO)2
      containing PMMA is an efficient luminescent material.

PMID- 15979399
TI  - Activation of phospholipase A(2) and MAP kinases by oxidized low-density
      lipoproteins in immortalized GP8.39 endothelial cells.
AB  - In immortalized rat brain endothelial cells (GP8.39), we have previously shown
      that oxidized LDL (oxLDL), after 24-h treatment, stimulates arachidonic acid
      release and phosphatidylcholine hydrolysis by activation of cytosolic
      phospholipase A(2) (cPLA(2)). A putative role for MAPKs in this process has
      emerged. Here, we studied the contribution of Ca(2+)-independent phospholipase
      A(2) (iPLA(2)), and the role of the MAP kinase family as well as both cPLA(2) and
      iPLA(2) mRNA expression by RT-PCR in oxLDL toxicity to GP8.39 cells in vitro. The
      activation of extracellular signal-regulated kinases ERK1/2, p38 and c-Jun NH(2)
      terminal kinase (JNK) was assessed with Western blotting and kinase activity
      assays. iPLA(2) activity, which was found as a membrane-associated enzyme, was
      more stimulated by oxLDL compared with native LDL. The phosphorylation of ERK1/2,
      p38 and JNKs was also significantly enhanced in a dose-dependent manner. PD98059,
      an ERK inhibitor, SB203580, a p38 inhibitor, and SP600125, an JNK inhibitor,
      abolished the stimulation of all three members of the MAPK family by oxLDL.
      Confocal microscopy analysis and subcellular fractionation confirmed either an
      increase in phosphorylated form of ERKs, p38 and JNKs, or their nuclear
      translocation upon activation. A strong inhibition of MAPK activation was also
      observed when endothelial cells were treated with GF109203X, a PKC inhibitor,
      indicating the important role of both PKC and all three MAPKs in mediating the
      maximal oxLDL response. Finally, compared with samples untreated or treated with
      native LDL, treatment with oxLDL (100 muM hydroperoxides) for 24 h significantly
      increased the levels of constitutively expressed iPLA(2) protein (by 5.1-fold)
      and mRNA (by 3.1-fold), as well as cPLA(2) protein (by 4.4-fold) and mRNA (by 1.5
      fold). Together, these data link the stimulation of PKC-ERK-p38-JNK pathways and
      PLA(2) activity by oxLDL to the prooxidant mechanism of the lipoprotein complex,
      which may initially stimulate the endothelial cell reaction against noxious
      stimuli as well as metabolic repair, such as during inflammation and
      atherosclerosis.

PMID- 15979400
TI  - Reliability of elbow stretch reflex assessment in chronic post-stroke
      hemiparesis.
AB  - OBJECTIVE: To establish reliability of quantitative measures of elbow joint
      spastic hypertonia in post-stroke hemiparesis. METHODS: Nine subjects with post
      stroke hemiparesis (mn duration: 42 months) were tested on three separate days.
      Biceps brachii and brachioradialis EMG were recorded during passive ramp-and-hold
      extensions applied at seven speeds between 30 and 210 degrees /s. EMG burst
      duration, onset position threshold, and burst intensity were used to evaluate
      reflex activity. Torque at 40 degrees of elbow flexion was used as a mechanical
      indicator of spastic hypertonia. RESULTS: Across speeds ICCs were consistent,
      means ranged between 0.63 and 0.85. Thus, relative reliability was fair to
      excellent for all parameters. Absolute reliability, determined using standard
      error of measurement expressed as a percentage of the mean score (%SEM), improved
      at higher speeds (> or = 120 degrees/s). CONCLUSIONS: These results establish
      reliability of reflex and mechanical measures of elbow spastic hypertonia post
      stroke. The data demonstrate greater reflex detection at high speeds, indicating
      greater potential to document meaningful changes in these distinct aspects of
      spastic hypertonia following intervention. SIGNIFICANCE: Based on findings of
      this study, reliability was demonstrated using four parameters of reflex EMG and
      torque indicating measurement consistency across sessions. These observations
      motivate determination of requisite effect sizes for clinical trials that
      evaluate treatment outcome.

PMID- 15979401
TI  - Lateralization of event-related beta desynchronization in the EEG during pre-cued
      reaction time tasks.
AB  - OBJECTIVE: Here, we investigate whether the event-related desynchronization (ERD)
      of spectral components of the cortical EEG in the beta (13-30 Hz) frequency range
      may, in part, index motor selection processes. Specifically, we sought evidence
      for a contralaterally dominant component of the beta ERD that is limited to
      trials in which motor selection is possible prior to any imperative cue to move,
      with attendant behavioural advantage. METHODS: We measured reaction time and
      assessed the lateralization of beta ERD in 12 healthy volunteers as they
      performed pre-cued choice reaction time tasks, in which warning S1 cues were
      either fully predictive about the laterality of a subsequent imperative S2 signal
      or provided no laterality information. We calculated 'lateralized ERD index'
      (LERDI), a parallel measure to the lateralized readiness potential in the time
      domain. RESULTS: Trials with 100% S1-S2 congruency produced significantly shorter
      reaction times than trials with 50% S1-S2 congruency, where laterality
      information was unreliable. Beta LERDI indicated significantly greater
      lateralisation of the ERD in the warning-go interval and of event-related
      synchronization (ERS) following movement in the 100% condition than in the 50%
      condition. The lateralization of the beta ERD with respect to hand persisted,
      even when subjects were instructed to make movements of opposite laterality to
      those prompted. CONCLUSIONS: Lateralized EEG changes occur in the beta band in
      the S1-S2 interval prior to movement, but only when informative warning cues
      allow early motor selection, as suggested by the shortening of reaction time.
      Furthermore, the enhanced contralateral ERS with 100% S1-S2 congruency suggests
      that this phenomenon is at least partly independent of afferent feedback, as the
      same movement was made in the 100 and 50% conditions. SIGNIFICANCE: Lateralized
      suppression of beta power prior to externally generated movements is associated
      with motor selection.

PMID- 15979402
TI  - The ipsilateral silent period in boys with attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: Characterize maturation of transcallosal inhibition (ipsilateral
      silent period [iSP]) in attention deficit/hyperactivity disorder (ADHD) using
      transcranial magnetic stimulation (TMS). BACKGROUND: Maturation of the iSP is
      related to acquisition of fine motor skills in typically developing children
      suggesting that dexterous fine motor skills depend upon mature interhemispheric
      interactions. Since neuromotor maturation is abnormal in boys with ADHD we
      hypothesized that iSP maturation in these children would be abnormal. We studied
      iSP maturation in 12 boys with ADHD and 12 age-matched, typically developing
      boys, 7-13 years of age. METHODS: Surface electromyographic activity was recorded
      from right first dorsal interosseus (FDI). During background activation, focal
      TMS was delivered at maximal stimulator output over the ipsilateral motor cortex.
      RESULTS: Maturation of finger speed in boys with ADHD was significantly slower
      than that in the control group. The iSP latency decreased with age in the control
      group but not in the ADHD group. CONCLUSIONS: These findings suggest the presence
      of a complex relationship between abnormalities of certain interhemispheric
      interactions (as represented by iSP latency) and delayed maturation of neuromotor
      skills in boys with ADHD. SIGNIFICANCE: These data provide preliminary
      physiologic evidence supporting delayed or abnormal development of
      interhemispheric interactions in boys with ADHD.

PMID- 15979403
TI  - Analysis of regularity in the EEG background activity of Alzheimer's disease
      patients with Approximate Entropy.
AB  - OBJECTIVE: The aim of this study was to analyse the regularity of the EEG
      background activity of Alzheimer's disease (AD) patients to test the hypothesis
      that the irregularity of the AD patients' EEG is lower than that of age-matched
      controls. METHODS: We recorded the EEG from 19 scalp electrodes in 10 AD patients
      and 8 age-matched controls and estimated the Approximate Entropy (ApEn). ApEn is
      a non-linear statistic that can be used to quantify the irregularity of a time
      series. Larger values correspond to more complexity or irregularity. A spectral
      analysis was also performed. RESULTS: ApEn was significantly lower in the AD
      patients at electrodes P3 and P4 (P < 0.01), indicating a decrease of
      irregularity. We obtained 70% sensitivity and 100% specificity at P3, and 80%
      sensitivity and 75% specificity at P4. Results seemed to be complementary to
      spectral analysis. CONCLUSIONS: The decreased irregularity found in the EEG of AD
      patients in the parietal region leads us to think that EEG analysis with ApEn
      could be a useful tool to increase our insight into brain dysfunction in AD.
      However, caution should be applied due to the small sample size. SIGNIFICANCE:
      This article represents a first step in demonstrating the feasibility of ApEn for
      recognition of EEG changes in AD.

PMID- 15979404
TI  - Scalp position and efficacy of transcranial magnetic stimulation.
AB  - OBJECTIVE: To assess the impact of the scalp site on the biological effects of
      TMS. METHODS: We performed high-resolution, three-dimensional whole head magnetic
      resonance imaging (MRI) in a healthy subject, systematically measured the scalp
      to-cortex distance across the head and calculated the resulting electric field in
      the superficial cortex. RESULTS: The variability in scalp-to-cortex distance led
      to differences in calculated cortical electric field strengths of a factor of
      two. A major portion of this variability was explained by a lateral to medial
      gradient with scalp-to-cortex distances being greatest close to the midline and
      smallest towards the temporal coordinates. CONCLUSIONS: Because of the medio
      lateral gradient in scalp-to-cortex distance interventions tailored on the basis
      of effects of TMS in the motor system will systematically induce stronger than
      expected electric currents when performed laterally to the motor spot.
      SIGNIFICANCE: The biological effects of TMS outside the motor spot may be
      markedly different from those observed in the motor system and this should be
      taken into account to optimize TMS for the evaluation or treatment of
      neuropsychiatric disorders.

PMID- 15979405
TI  - The origin of spontaneous discharges in acquired neuromyotonia. A Macro EMG
      study.
AB  - OBJECTIVE: To study the generator sites of spontaneous discharges in patients
      with immune-mediated neuromyotonia. METHODS: Macro EMGs triggered by both
      spontaneously and voluntarily activated single action potentials were recorded
      and the mean peak-to-peak amplitude and area of the macro motor unit potentials
      were compared in two patients with typical acquired neuromyotonia having positive
      antibodies against voltage-gated potassium channels. RESULTS: Mean peak-to-peak
      amplitude and area of Macro EMG motor unit potentials (macro MUPs) triggered by
      spontaneous discharges were significantly smaller than those triggered by
      voluntary activation in both patients. However, a few macro MUPs triggered by
      spontaneous discharges resembled those triggered by voluntary activation.
      CONCLUSIONS: Spontaneous discharges in two patients with immune-mediated
      neuromyotonia seem to be mostly generated at sites distal to the terminal axon
      branching points. SIGNIFICANCE: This finding may provide a new insight in the
      understanding of spontaneous discharges in immune-mediated neuromyotonia.

PMID- 15979406
TI  - The role of HIF-1alpha in myeloid cell inflammation.
AB  - Myeloid cells are key effectors of the innate immune response, and as such are
      often required to migrate to, and function within, sites that are markedly
      hypoxic. To adapt to such oxygen deplete environments they have developed
      functional and survival responses that are regulated by the hypoxia-inducible
      factor (HIF) oxygen-sensing pathway. In this review, we describe three key
      aspects of HIF-dependent regulation of myeloid cell function: (i) the maintenance
      of ATP pools and the subsequent regulation of proinflammatory responses, (ii) the
      HIF-dependent inhibition of neutrophil apoptosis and (iii) the HIF-mediated
      regulation beta2 integrin expression.

PMID- 15979407
TI  - Hematopoietic stem cells and their niche.
AB  - Recent evidence indicates that osteoblasts are crucial components of the
      particular microenvironments, or niches, for hematopoietic stem cells (HSCs) in
      adult bone marrow (BM). Stem cells persist in an immature state within the BM.
      The quiescence of HSCs is controlled dynamically by the signaling of receptors
      ligands and cell-adhesion molecules. In this review, the characteristics of HSCs
      in the niche are discussed. The understanding of the relationship between normal
      and cancer stem cells and their niches should lead to the development of new
      strategies directed toward regeneration medicine and cancer therapeutics.

PMID- 15979408
TI  - Viral evasion of NK-cell activation.
AB  - Viruses, such as human cytomegalovirus (HCMV), have developed mechanisms to evade
      recognition by, and activation of, natural killer (NK) cells, which are cells
      that provide crucial innate immune defense. Such mechanisms help viruses persist
      in the human host and attain a state of chronic infection. A recent report
      documents an antagonistic effect of the main HCMV tegument protein, pp65, on
      NKp30, a natural cytotoxicity-inducing receptor expressed uniquely on NK cells.

PMID- 15979409
TI  - Interfacing T-cell effector and regulatory function through CD137 (4-1BB) co
      stimulation.
AB  - Historically, co-stimulation has been regarded as a prerequisite for T-cell
      activation. A lack of co-stimulation results in peripheral T-cell tolerance,
      which manifests as unresponsiveness or death through apoptosis. Recent findings,
      however, suggest that eliciting co-stimulation can also induce tolerance.
      Reconciling these diametrically opposed results is certainly of academic
      importance but more importantly transcends basic immunology and impacts present
      and future clinical trials that are centered on modulating T-cell co-stimulation.
      This review will focus on CD137 (4-1BB) and propose a mechanism of action in
      which CD137-primed CD8 T cells express effector function and also inhibit CD4 T
      cell activation. This model suggests that the same CD8 T cells possess antitumor
      effector function interfaced with regulatory capacity, which ultimately leads to
      concomitant inhibition of tumorigenesis and autoimmune disease.

PMID- 15979410
TI  - Recognition and rejection of self in plant self-incompatibility: comparisons to
      animal histocompatibility.
AB  - In many flowering plants, intraspecific barriers to self-fertilization ensure
      outbreeding by interrupting the path of pollen tube growth before egg-sperm
      interaction. These self-sterility or self-incompatibility (SI) systems are unique
      among recognition systems, in that they are based on the recognition and
      rejection of self, rather than non-self. Consistent with multiple evolutionary
      origins of SI, different plant families use distinct mechanisms for pollen
      recognition and inhibition. These mechanisms range from the arrest of pollen tube
      emergence by specific interactions between surface receptors and ligands and
      activation of intracellular signaling cascades, to the destruction of pollen
      tubes by the cytotoxic activity of RNases or by induction of a programmed cell
      death pathway. These mechanistic differences notwithstanding, all plant SI
      systems analyzed to date share a high degree of recognition specificity, effected
      by a large number of highly diverged, genetically linked and co-evolving genes,
      with immunity and other systems that discriminate between self and non-self.

PMID- 15979411
TI  - Mining the malaria transcriptome.
AB  - Malaria remains the most devastating parasitic disease worldwide, and is
      responsible each year for >500 million infections and between one million and two
      million deaths of children under five years of age. Plasmodium falciparum is the
      most prevalent and deadly malaria parasite of humans, and a huge amount of data
      about it is now publicly available following completion of its genome sequence,
      the complete transcriptome of its asexual blood stages and proteomic analyses of
      its different life stages. Thus, new computational approaches are needed to
      analyze these data to yield biologically meaningful results that can be validated
      experimentally and, hopefully, lead to alternative control strategies. In this
      article, we highlight the importance of new computational approaches in mining
      the malaria transcriptome of the intraerythrocytic developmental cycle of P.
      falciparum.

PMID- 15979412
TI  - A chimeric T cell antigen receptor that augments cytokine release and supports
      clonal expansion of primary human T cells.
AB  - The transduction of primary T cells to express chimeric T cell receptors (cTCR)
      for redirected targeting of tumor cells is an attractive strategy for generating
      tumor-specific T cells for adoptive therapy. However, tumor cells rarely provide
      costimulatory signals and hence cTCRs that transmit just a CD3zeta signal can
      only initiate target cell killing and interferon-gamma release and fail to induce
      full activation. Although incorporation of a CD28 component results in IL-2
      release and limited proliferation, T cell activation remains incomplete. OX40
      transmits a potent and prolonged T cell activation signal and is crucial for
      maintaining an immunological response. We hypothesize that the CD28-OX40-CD3zeta
      tripartite cytoplasmic domain will provide a full complement of activation,
      proliferation, and survival signals for enhanced anti-tumor activity.

PMID- 15979413
TI  - Localized gene expression following administration of adeno-associated viral
      vectors via pancreatic ducts.
AB  - Gene transfer into pancreatic cells in vivo could be of immense therapeutic
      benefit in cases of type 1 diabetes (T1D) through the production of molecules
      capable of interrupting the progression of autoimmunity or promoting regeneration
      of insulin-secreting beta cells. We adapted a clinically relevant surgical
      technique (endoscopic retrograde cholangiopancreatography) to deliver rAAV
      encoding human alpha1-antitrypsin (approved gene symbol SERPINA1) to the pancreas
      of 3-week-old Fisher 344 rats and C57BL/6 mice. We compared natural as well as
      bioengineered serotypes of rAAV (rAAV1, rAAV2/Apo, rAAV8) as well as different
      promoters (chicken beta-actin, human insulin) for their expression in vivo. Rats
      injected with rAAV1 showed the highest hAAT expression (week 2, rAAV1/CB-AT, 579
      +/- 457 ng/ml). In mice, rAAV8 vector delivered the highest serum concentration
      of hAAT (week 2, rAAV8/CB-AT, 19 +/- 6 microg/ml). The chicken beta-actin
      promoter provided the highest expression in both rodent experiments.
      Immunohistochemical staining indicated transduction primarily of pancreatic
      acinar cells with either the rAAV1/CB-AT vector in the rat or the rAAV8/CB-AT
      vector in the mouse. This study demonstrates that rAAV vectors can be designed to
      deliver therapeutic genes efficiently to the pancreas and achieve high levels of
      gene expression and may be useful in treating pancreatic disorders, including
      T1D.

PMID- 15979414
TI  - Characterization of a galactose binding serum lectin from the Indian catfish,
      Clarias batrachus: possible involvement of fish lectins in differential
      recognition of pathogens.
AB  - A lectin with molecular mass around 200 kDa was isolated from the serum of the
      Indian catfish Clarias batrachus. The bioactivity of this serum lectin was Ca2+
      and pH dependent. The lectin appeared to be specific for alpha-methyl galactose
      and sialoglycoproteins like porcine and bovine submaxillary mucin and could
      agglutinate human, rabbit, mice, rat and chicken erythrocytes. This fish lectin
      was able to specifically agglutinate different gram negative bacteria. When it
      was checked against different strains of the fish pathogen Aeromonas sp., it
      significantly altered the viability and pathogenicity of the bacteria. Binding of
      the lectin to Aeromonas sp., resulted in a dose dependent increase in the
      bactericidal activity of fish macrophages. However, when the lectin was checked
      against different gram positive bacteria it could not agglutinate or affect the
      viability of those strains and also failed to bring about any significant change
      in the bactericidal potential of fish macrophages. The lectin was able to induce
      the proliferation of head kidney lymphocytes of Clarias and helped in the release
      of 'IL-1' like cytokines from head kidney macrophages.

PMID- 15979415
TI  - Survey for potentially necrotizing spider venoms, with special emphasis on
      Cheiracanthium mildei.
AB  - It has proven difficult to identify those spiders which cause necrotic lesions.
      In an effort to design a simple, inexpensive screening method for identifying
      spiders with necrotizing venoms, we have examined the venom gland homogenates of
      a variety of spider species for their ability to cause red blood cell lysis.
      Those venoms which were positive were further examined for the presence of
      sphingomyelinase D, and their ability to evoke necrotic lesions in the skin of
      rabbits. Sphingomyelinase D is known to be the causative agent of necrosis and
      red blood cell lysis in the venom of the brown recluse spider (Loxosceles
      reclusa), and our assumption was that this would be the same agent in other
      spider venoms as well. This did not prove to be the case. Of 45 species examined,
      only the venom of L. reclusa and Cheiracanthium mildei lysed sheep red blood
      cells. Unlike L. reclusa venom, however, C. mildei venom did not possess
      sphingomyelinase D nor did it cause necrotic lesions in the skin of rabbits. We
      present evidence suggesting that a phospholipase A2 is the hemolytic agent in C.
      mildei venom.

PMID- 15979416
TI  - Molecular cloning and expression of a novel CYP26 gene (cyp26d1) during zebrafish
      early development.
AB  - Proper restriction of retinoid signaling by Cyp26s is essential for development
      of vertebrate embryos while inappropriate retinoid signaling can cause
      teratogenesis. Here, we report cloning and expression analysis of a novel cyp26
      gene (cyp26d1) isolated from zebrafish. The predicted protein encoded by cyp26d1
      consists of 554 amino acids. It exhibits 54% amino acid identity with human
      Cyp26C1, 50% with zebrafish Cyp26B1 and 38% with zebrafish Cyp26A1. Whole-mount
      in situ hybridization shows that cyp26d1 is first expressed in sphere stage, then
      disappears at 50% epiboly and resumes its expression at 75% epiboly. During
      segmentation period, cyp26d1 message is found at presumptive hindbrain. Double in
      situ hybridization with krox20 and cyp26d1 reveals that cyp26d1 is expressed in
      presumptive rhombomere 2-4 (r2-r4) at 2-somite stage. At 3-somite stage, cyp26d1
      gene is expressed in r6 and pharyngeal arch (pa) one in addition to its
      expression at r2 and r4. At 6-somite stage, cyp26d1 message is present in
      continuous bands at r2-r6 and in pa1. This expression pattern is maintained from
      10-somite stage through 21-somite stage except that the expression level is
      greatly reduced at r2 and r4. At 21-somite stage, cyp26d1 is also found in a
      group of cells in telencephalon and diencephalons. At 25-31h post-fertilization
      (hpf), the zebrafish cyp26d1 expression domain is extended to eyes, otic vesicles
      and midbrain in addition to its expression in hindbrain, telencephalon,
      diencephalons, and pharyngeal arches. At 35-48hpf, the expression of cyp26d1 is
      mainly restricted to otic vesicles, pharyngeal arches and pectoral fins and the
      expression level is greatly reduced.

PMID- 15979417
TI  - Identification of Dll1 (Delta1) target genes during mouse embryogenesis using
      differential expression profiling.
AB  - The Notch signaling pathway has pleiotropic functions during mammalian
      embryogenesis. It is required for the patterning and differentiation of the
      presomitic and somitic paraxial mesoderm and of the neural tube. We used DNA-chip
      expression profiling and 2D-gel electrophoresis combined with peptide mass
      fingerprinting to identify genes and proteins differentially regulated in E10.5
      Dll1 (delta-like 1, Delta1) mutant embryos. The differential expression profiling
      approach identified 47 regulated transcripts and 40 differentially expressed
      proteins. The majority of these genes has until now not been associated with
      Notch signaling. Subsequent whole-mount in situ hybridization confirmed that a
      subset of the identified transcripts has restricted and distinct patterns of
      expression in E10.5 mouse embryos. For most genes these expression patterns were
      affected in the presomitic mesoderm, in differentiating somites of Dll1 mutant
      embryos and in the neural tube and cells differentiating from it. Similar effects
      were observed in embryos homozygous for the Headturner (Htu) and pudgy (pu)
      mutations, which are alleles of the Notch ligands Jag1 and Dll3. The regulated
      expression of a subset of the proteins was validated by immunoblots. Remarkably
      six of the proteins down-regulated in Dll1 mutant embryos are proteasome
      subunits. The large set of regulated genes identified in this differential
      expression profiling approach is an important resource for further functional
      studies.

PMID- 15979418
TI  - Airway closure in microgravity.
AB  - Recent single breath washout (SBW) studies in microgravity and on the ground have
      suggested an important effect of airway closure on gas mixing in the human lung,
      reflected particularly in the phase III slope of vital capacity SBW and bolus
      tests. In order to explore this effect, we designed a SBW in which subjects
      inspired 2-l from residual volume (RV) starting with a 150 ml bolus of He and
      SF6. In an attempt to vary the pattern of airways closure configuration before
      the test, the experiments were conducted in 1G and in microgravity during
      parabolic flight allowing the pre-test expiration to RV to be either in
      microgravity or at 1.8 G, with the actual test gas inhalation performed entirely
      in microgravity. Contrary to our expectations, the measured phase III slope and
      phase IV height and volume obtained from seven subjects in microgravity were
      essentially identical irrespective of the gravity level during the pre-test
      expiration to RV. The results suggest that airway closure configuration at RV
      before the test inspiration has no apparent impact on phases III and IV
      generation.

PMID- 15979419
TI  - Effects of pure n-alkanes and crude oil on bacterial phospholipid classes and
      molecular species determined by electrospray ionization mass spectrometry.
AB  - Phospholipids are major components of bacterial membrane. Furthermore, the growth
      in vitro on xenobiotics such as n-alkanes, aromatic compounds or alkanols bring
      about to a bacterial membrane adaptive response. Concerning this work, we studied
      the membrane lipid composition of a hydrocarbon-degrading gram-positive bacterium
      (Corynebacterium sp.) on a soluble substrate and we detected four different
      phospholipid classes: phosphatidylglycerol, phosphatidylinositol, cardiolipin and
      acyl phosphatidylglycerol. In addition, a study of the lipid composition was
      performed after an in vitro culture on either pure n-alkane or crude oil. The
      growths on such hydrophobic substrates showed major qualitative and quantitative
      modifications. In the case of a growth on either heneicosane or crude oil, an
      increase of odd-numbered fatty acids was observed. Furthermore, the phospholipid
      polar head group composition was highly influenced by the crude oil addition.
      These modifications were, respectively, interpreted as the consequence of
      hydrocarbon assimilation and membrane fluidity adaptation. Finally,
      Corynebacterium sp. was taken back on the initial ammonium acetate substrate in
      order to determine its restoration abilities after a petroleum contamination.

PMID- 15979420
TI  - Advanced MR techniques in the term-born neonate with perinatal brain injury.
AB  - Magnetic resonance imaging (MRI) has become an essential tool for assessing the
      neonatal brain. Conventional imaging can detect patterns of injury that relate to
      the aetiology and timing of an insult and provide valuable information about
      prognosis. Sequences must always be adapted for the immature brain. Diffusion
      techniques improve the detection of ischaemic tissue and allow more accurate
      timing of an insult. Diffusion tensor imaging allows the assessment of tissue
      microstructure changes with normal development as well as in response to tissue
      injury. Diffusion tractography will further our understanding of the long-term
      effects of perinatal injuries on brain development, and when used in combination
      with clinical and functional imaging studies will allow the plasticity of the
      immature brain to be studied. MR angiography and venography are important
      adjuncts to the clinical examination, and when combined with perfusion studies
      can provide valuable information about vessel development following injury.
      Detailed vascular studies may detect inherent susceptibilities, which give rise
      to lesions in some babies but not others. The future for neonatal imaging is
      exciting; however, detailed and serial imaging of carefully chosen cohorts of
      infants coupled with long-term clinical follow-up are essential to ensure the
      clinical significance of any new findings.

PMID- 15979422
TI  - Usefulness of positron emission tomography in predicting long-term outcome in
      patients with diabetes mellitus and ischemic left ventricular dysfunction.
AB  - We assessed the value of positron emission tomography to predict long-term
      outcome in patients with diabetes and ischemic left ventricular (LV) dysfunction.
      Circumferential profiles of nitrogen-13 ammonia (NH3) and fluorine-18
      fluorodeoxyglucose uptakes were obtained in 61 patients who had diabetes and
      ischemic LV dysfunction. Patient profiles were compared with those from a normal
      database. NH3 and fluorine-18 fluorodeoxyglucose defect sizes and extent of
      perfusion-metabolism mismatch (percentage of myocardium with fluorine-18
      fluorodeoxyglucose uptake minus NH3 uptake >2 SD above the normal difference)
      were determined. Patients were followed every 6 months. Over a mean follow-up of
      4.3 years, cardiac death occurred in 52% of patients who underwent
      revascularization and 61% of those who underwent medical therapy (p = 0.69). No
      clinical or imaging variables predicted cardiac death in patients who underwent
      revascularization. In those who received medical therapy, mismatch in > or =3% of
      the left ventricle (risk ratio 4.0, p = 0.01) was the only multivariate predictor
      of cardiac death. Revascularization improved survival of patients who had
      mismatch of > or =3% at 4 years (p = 0.003) and at 8 years (p = 0.012) of follow
      up. Patients who had mismatch > or =3% and ejection fraction <30% had the
      greatest improvement in survival with revascularization compared with medical
      therapy (p <0.0001). Revascularization also improved 4-year survival of patients
      who had NH3 perfusion defects of > or =25% of the left ventricle (p = 0.02). In
      conclusion, mismatch identifies medically treated patients who have diabetes and
      LV dysfunction, who are at high risk for cardiac death. Intermediate- and long
      term survival of patients who have diabetes and mismatch may be improved with
      revascularization, and those who have significant mismatch and severe LV
      dysfunction have the greatest benefit.

PMID- 15979423
TI  - Prognostic value of exercise echocardiography in patients with diabetes mellitus
      and known or suspected coronary artery disease.
AB  - To assess the prognostic value of exercise echocardiography in subjects who had
      diabetes, we studied 214 patients who had 28 hard cardiac events (cardiac death
      in 15, myocardial infarction in 13) during a follow-up of 44 +/- 16 months.
      Independent risk factors for predicting cardiac events were insulin therapy (odds
      ratio 2.313), peak left ventricular ejection fraction (odds ratio 0.973), and
      ischemia detected by exercise echocardiography (odds ratio 2.513).

PMID- 15979424
TI  - Comparison of prognostic value of negative dobutamine stress echocardiography
      versus single-photon emission computed tomography after acute myocardial
      infarction.
AB  - We enrolled 196 patients who had myocardial infarction and no ischemia on
      dobutamine stress echocardiography (DSE) and/or single-photon emission computed
      tomography (SPECT). Negative studies were observed in 125 patients on DSE and in
      159 on SPECT. Patients were followed for 43 +/- 14 months. Cardiac events
      occurred in 14% of patients who did not have ischemia on DSE and in 9% of
      patients who did not have ischemia on SPECT. Event-free survival rate was higher
      in the presence of negative findings on SPECT compared with DSE (p <0.05). The
      lack of residual myocardial ischemia on SPECT identifies patients at low risk of
      events, and a negative finding on stress SPECT is superior to a negative finding
      on DSE.

PMID- 15979425
TI  - Usefulness of real-time intravenous myocardial contrast echocardiography in
      predicting left ventricular dilation after successfully reperfused acute
      myocardial infarction.
AB  - The ability of real-time intravenous myocardial contrast echocardiography to
      predict left ventricular remodeling after reperfused acute myocardial infarction
      was assessed in 47 patients. Intravenous myocardial contrast echocardiography was
      an independent predictor of left ventricular dilation after acute myocardial
      infarction. In particular, normal contrast opacification within dyssynergic
      segments indicated a very low risk of remodeling.

PMID- 15979426
TI  - Effect of intracoronary aqueous oxygen on left ventricular remodeling after
      anterior wall ST-elevation acute myocardial infarction.
AB  - The present report describes outcomes of randomized selective intracoronary
      aqueous oxygen versus standard care in patients who had acute anterior wall
      myocardial infarction within 6 hours of onset (n = 50). Left ventricular (LV)
      dimensions and function were assessed by contrast echocardiography at baseline
      and 1 month. It is demonstrated that aqueous oxygen prevents LV remodeling and
      preserves LV ejection fraction.

PMID- 15979427
TI  - Usefulness of four echocardiographic risk assessments in predicting 30-day
      outcome in acute myocardial infarction.
AB  - One thousand fifty-one consecutive patients who had acute myocardial infarction
      were classified into 3 risk groups by 4 echocardiographic risk assessments: left
      ventricular ejection fraction, left ventricular filling pattern, estimated
      systolic pulmonary artery pressure, and mitral regurgitation, with 30-day
      mortality rates of 13.7%, 3.8%, and 1%, respectively (p <0.001). Independent
      echocardiographic and clinical predictors of 30-day mortality included age (10
      years, hazard ratio [HR] 1.30, 95% confidence interval [CI] 0.91 to 1.89), female
      gender (HR 2.12, 95% CI 0.94 to 4.74), Killip's class > or =II on admission (HR
      3.09, 95% CI 1.38 to 7.11), group 2 (moderate) risk (HR 2.89, 95% CI 1.07 to
      8.56), and group 1 (high) risk (HR 8.16, 95% CI 2.95 to 25.23).

PMID- 15979428
TI  - N-terminal pro-B-type natriuretic peptide and matrix metalloproteinases in early
      and late left ventricular remodeling after acute myocardial infarction.
AB  - N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a predictor of left
      ventricular remodeling. Matrix metalloproteinases (MMPs) contribute to collagen
      breakdown that is associated with ventricular remodeling after acute myocardial
      infarction (AMI). We assessed the association between circulating levels of NT
      pro-BNP, MMP-2, and MMP-9 and their inhibitor (tissue inhibitor of
      metalloproteinase-1) early (24 and 72 hours) and late (7 and 30 days) after AMI
      in 108 patients who had ST-elevation AMI (90 men; mean age 60 years). Serum MMP-2
      levels measured 24 and 72 hours after AMI were inversely associated with NT-pro
      BNP levels, whereas MMP-9 serum levels were positively related. During late-stage
      remodeling after AMI, circulating concentrations of tissue inhibitor of
      metalloproteinase-1 were independently associated with NT-pro-BNP levels 7 and 30
      days after AMI. This study shows that, in patients who have ST-elevation AMI,
      circulating levels of NT-pro-BNP are associated with MMPs in a species-specific
      and time-dependent manner.

PMID- 15979429
TI  - Mortality after emergent percutaneous coronary intervention in cardiogenic shock
      secondary to acute myocardial infarction and usefulness of a mortality prediction
      model.
AB  - Although percutaneous coronary intervention (PCI) in the setting of cardiogenic
      shock has a high in-hospital mortality rate, it has been shown to decrease the
      mortality rate in certain subgroups. The identity and relative importance of
      variables that are predictive of in-hospital mortality rate after PCI for
      cardiogenic shock are uncertain. Accordingly, we examined data of >300,000
      patients in the American College of Cardiology-National Cardiovascular Data
      Registry (ACC-NCDR) that were collected from 1998 to 2002 and evaluated the
      outcomes in 483 consecutive patients who underwent emergency PCI for cardiogenic
      shock. Patients' mean age was 65 +/- 13 years, with men predominating (61%). All
      underwent emergency/salvage PCI in the setting of cardiogenic shock after acute
      myocardial infarction. Mean left ventricular ejection fraction was 30 +/- 16%.
      Stents were placed in 64% of patients, and thrombolytic agents were administered
      in 26%. Although PCI was angiographically successful in 79% of patients, the in
      hospital mortality rate was 59.4%. Length of stay after PCI was 7.2 +/- 8 days.
      Logistic regression using all available variables identified 6 multivariate
      predictors of death: age (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.68
      to 3.28, p <0.001) for each 10-year increment, female gender (OR 1.55, 95% CI
      1.00 to 2.41, p <0.001), baseline renal insufficiency (creatinine >2.0 mg/dl; OR
      4.69, 95% CI 1.96 to 11.23, p <0.001), total occlusion in the left anterior
      descending artery (OR 1.99, 95% confidence interval 1.28 to 3.09, p <0.01), no
      stent used (OR 2.55, 95% CI 1.63 to 3.96, p <0.01), and no glycoprotein IIb/IIIa
      inhibitor used during PCI (OR 1.96, 95% CI 1.30 to 2.98, p <0.01). In a second
      analysis using only variables known to the clinician at the time of initial
      presentation, gender, age, renal insufficiency, and total occlusion of the left
      anterior descending coronary artery were significant. In conclusion, analysis of
      patients from the ACC-NCDR who underwent emergency PCI for acute myocardial
      infarction in the presence of cardiogenic shock shows an in-hospital mortality
      rate of approximately 60% when PCI is attempted.

PMID- 15979430
TI  - Relation of T-wave inversion in Q-wave acute myocardial infarction to myocardial
      viability on resting rubidium-82 and 18-fluoro-deoxyglucose positron emission
      tomography imaging.
AB  - T-wave inversion in areas of Q-wave myocardial infarction has been advocated as a
      predictor of myocardial viability. However, the predictive value of this
      electrocardiographic finding in distinguishing viable from nonviable muscle is
      not fully defined. Thus, we correlated electrocardiographic Q waves and a measure
      of T-wave inversion with the results of rubidium-82 (Rb-82) and 18-fluoro
      deoxyglucose-positron emission tomography (FDG-PET) imaging at rest. We analyzed
      35 Q-wave myocardial infarct regions in 25 patients. Nineteen of the 35 (54%)
      were judged viable by Rb-82/FDG-PET. Using the Novacode T-wave score, T-wave
      inversion was present in 11 of 19 regions (58%) with viability and 5 of 16
      regions (31%) without viability. Thus, neither Q waves nor T-wave inversion can
      accurately predict myocardial viability in patients with Q-wave myocardial
      infarction.

PMID- 15979431
TI  - Relation of atmospheric pressure changes and the occurrences of acute myocardial
      infarction and stroke.
AB  - Previous studies have demonstrated variation in vascular events with respect to
      season and time of day. Changes in barometric pressure display daily and seasonal
      variations and could modulate the occurrence of vascular events. The objective of
      this study was to determine whether a relation exists between changes in
      barometric pressure and occurrence of stroke or acute myocardial infarction
      (AMI). A retrospective analysis of hospital admissions for AMI and stroke from
      1993 to 1996 in central Texas was related to changes in atmospheric pressure that
      were obtained from the National Climatic Data Center. Patients who had AMI (n =
      1,327) or stroke (n = 839) were identified from a computerized hospital database.
      Mean atmospheric pressure, greatest change in pressure, and rate of change in
      pressure per 24-hour period were computed. One-, 2-, and 3-day and seasonal
      groupings of cardiovascular events were related to corresponding changes in
      barometric pressure. The fall and winter seasons had the highest variability in
      atmospheric pressure readings. There was a significant correlation (p = 0.0083)
      between a decrease in atmospheric pressure and the occurrence of AMI the day
      after a pressure decrease, especially during the fall and winter seasons. No
      relation between stroke and atmospheric pressure was demonstrated. In conclusion,
      we conclude that rapid decreases in barometric pressure are associated with the
      occurrence of AMI but not of stroke.

PMID- 15979432
TI  - Family-based association studies of lipid gene polymorphisms in coronary artery
      disease.
AB  - Dysfunction of lipid-metabolizing proteins is implicated in the pathogenesis of
      coronary artery disease. Single nucleotide polymorphisms in genes that encode
      sterol regulatory binding protein-1a, adenosine triphosphate binding cassette-A1,
      hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein were
      assessed as potential markers of disease susceptibility in a family-based study
      of 1,012 patients from 386 families. Association between single nucleotide
      polymorphisms and coronary artery disease was tested by the combined transmission
      disequilibrium test/sib transmission disequilibrium test and pedigree
      disequilibrium test. After Bonferroni's correction, the pedigree disequilibrium
      test demonstrated significant excess transmission (p <0.0083) to affected
      patients of the hepatic lipase -514 T allele, which suggests that this may
      constitute a novel disease-susceptibility locus.

PMID- 15979433
TI  - Relation of number of complex coronary lesions to serum C-reactive protein levels
      and major adverse cardiovascular events at one year.
AB  - This study investigated the relation among serum C-reactive protein (CRP), number
      of complex coronary lesions, and adverse cardiovascular events at 1 year.
      Univariate and multivariate analyses were performed. Of 283 patients who had
      acute coronary syndrome, a single complex lesion was present in 32%, multiple
      complex lesions were identified in 23%, and no complex lesion was documented in
      45%. On multivariate analysis, CRP was independently associated with the presence
      of multiple complex coronary lesions (p <0.0001); there was a striking
      association between increments in CRP titers and number of complex lesions (CRP
      levels of 0.22 mg/dl in patients who had 0 lesion, 0.53 mg/dl in patients who had
      1 lesion, and 1.85 mg/dl in patients who had multiple complex lesions, p
      <0.0001), and high serum CRP levels independently predicted adverse outcome (p =
      0.03). In conclusion, the presence of multiple complex plaques was the most
      powerful predictor of adverse outcome (hazard ratio 2.88, p = 0.0007),
      predominantly in those who had high CRP levels (p = 0.004).

PMID- 15979434
TI  - Relation between coronary artery calcium and incident chest pain in a community
      dwelling screening population.
AB  - Incident chest pain occurred in 30.3% of 1,743 asymptomatic healthy men and women
      who were followed for up to 4 years. Proportions of patients who had coronary
      artery calcium were similar among those who had no chest pain, noncardiac pain,
      atypical pain, or cardiac chest pain. Incident chest pain is common and should be
      examined according to a patient's pretest probability of developing coronary
      artery disease, without excessive influence of the presence of coronary artery
      calcium.

PMID- 15979435
TI  - Hostility, age, and mortality in a sample of cardiac patients.
AB  - This study examined hostility as a predictor of survival in a sample of 1,328
      patients who had documented coronary artery disease. After controlling for
      disease severity, there was a significant interaction between age and hostility.
      Hostility was significantly associated with poorer survival but only in younger
      (<61.2 years) patients.

PMID- 15979436
TI  - Bivalirudin versus heparin as an antithrombotic agent in patients who undergo
      percutaneous saphenous vein graft intervention with a distal protection device.
AB  - Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a
      variety of percutaneous coronary interventions, and data on its usage in
      saphenous vein graft interventions are limited. This retrospective, observational
      study evaluated the efficacy and safety of bivalirudin compared with heparin as
      an antithrombotic regimen in patients who underwent saphenous vein graft
      intervention with distal protection devices. We found that bivalirudin use is
      clinically safe and feasible, with fewer vascular and ischemic complications
      compared with heparin.

PMID- 15979437
TI  - Usefulness of preprocedural platelet aggregation to predict restenosis after
      percutaneous coronary intervention.
AB  - We investigated whether the assessment of small platelet aggregates before
      percutaneous coronary intervention (PCI) could predict restenosis after PCI. This
      was a prospective cohort study that enrolled 189 consecutive patients who had
      coronary artery disease. In multiple logistic regression analysis, higher levels
      of preprocedural small platelet aggregates were independently associated with
      restenosis after PCI. Measurement of small platelet aggregates may serve as a
      useful clinical variable for stratifying patients who present for PCI.

PMID- 15979438
TI  - Intravascular ultrasonic assessment of stent diameters derived from
      manufacturer's compliance charts.
AB  - We used intravascular ultrasound (IVUS) to assess the accuracy of manufacturers'
      stent balloon compliance charts. Many interventional cardiologists rely on
      manufacturers' compliance charts to select stent size and optimize stent
      diameters according to inflation pressures during percutaneous procedures. We
      randomly selected 212 patients who had de novo coronary lesions that had been
      treated with a single, bare metal, > or =3.0-mm stent (Bx velocity, NIR,
      TETRA/PENTA, S660/S670/S7) under IVUS guidance. Cases of stent overlap and
      postdilatation with another balloon were excluded. Predicted stent diameters were
      derived from each manufacturer's compliance charts, and stent size and final
      maximal deployment pressures were derived from each physician's report. IVUS
      measured minimum stent diameters (range 1.4 to 4.0 mm, mean 2.79 +/- 0.48) were
      smaller than predicted diameters (range 3.1 to 4.57 mm, mean 3.79 +/- 0.44). The
      ratio of IVUS to predicted diameters ranged from 44% to 97% (mean 74 +/- 10%).
      This finding was common to all 3 stent sizes: 74 +/- 12% for 3.0 mm, 73 +/- 9%
      for 3.5 mm, and 74 +/- 9% for 4.0-mm stents (p = 0.9). This finding was also
      common to all 4 stent manufacturers, 72 +/- 8% for Boston Scientific, 76 +/- 11%
      for Guidant, 73 +/- 9% for Cordis, and 74 +/- 11% for Medtronic (p = 0.13), and
      to different stent lengths. Only 3.8% of the stents achieved 90% of the predicted
      minimum stent diameters, and only 24.6% achieved 80% of the predicted minimum
      stent diameters. In conclusion, in human coronary arteries, minimal stent
      diameter measured by IVUS is significantly smaller than that predicted by in
      vitro compliance charts. These differences are independent of stent manufacturer,
      length, diameter, and deployment pressure.

PMID- 15979439
TI  - Two-year-plus follow-up of a paclitaxel-eluting stent in de novo coronary
      narrowings (TAXUS I).
AB  - Early results with polymer-based paclitaxel-eluting stents have shown significant
      improvements in the clinical and angiographic parameters of restenosis, as well
      as excellent safety outcomes. However, the duration of these beneficial effects
      is unknown. Therefore, the clinical outcomes of the TAXUS I study population were
      evaluated at 2- and 3-year follow-up. In TAXUS I, 61 patients with single, focal
      coronary lesions were randomly assigned to receive either a paclitaxel-eluting
      TAXUS stent (n = 31) or a bare metal control stent (n = 30). Low rates of
      composite major adverse cardiac events (MACEs) reported at 1-year follow-up (3.2%
      TAXUS vs 10.0% control) were maintained at 2 and 3 years, with no additional
      MACEs in either treatment group 1 year after implantation. The single target
      vessel revascularization in the TAXUS group was remote from the target lesion in
      contrast to 3 target lesion revascularizations in the control group.

PMID- 15979440
TI  - Association between consumption of beer, wine, and liquor and plasma
      concentration of high-sensitivity C-reactive protein in women aged 39 to 89
      years.
AB  - Although cross-sectional studies have shown an inverse or U-shaped relation
      between alcohol consumption and plasma concentration of high-sensitivity C
      reactive protein (hs-CRP), the associations between specific types of alcoholic
      beverages--beer, wine, and liquor--and hs-CRP concentrations are less clear.
      Plasma concentrations of hs-CRP were measured in 11,815 participants in the
      Women's Health Study who had never used postmenopausal hormones. Alcohol intake
      was measured using a semiquantitative food-frequency questionnaire. Alcohol
      consumption had an inverse association with geometric mean hs-CRP concentrations
      (nondrinkers 1.43 mg/L, 0.1 to 6 g alcohol/day 1.37 mg/L, 6.1 to 12 g alcohol/day
      1.29 mg/L, >12 g alcohol/day 1.28 mg/L, p for trend = 0.003). In age-adjusted
      analyses, beverage preference was a significant predictor of geometric mean hs
      CRP concentration. However, after adjustment for body mass index (BMI), beer
      drinkers who consumed 6.1 to 12 g alcohol/day had a geometric mean hs-CRP
      concentration of 1.03 mg/L, wine drinkers 1.09 mg/L, liquor drinkers 1.28 mg/L,
      and combination drinkers 1.09 mg/L (p = 0.43). The association between alcohol
      and hs-CRP concentration appears to be mediated primarily by ethanol and was
      independent of the type of alcoholic beverage consumed once BMI was taken into
      account.

PMID- 15979441
TI  - Acute effect of atorvastatin on coronary circulation measured by transthoracic
      Doppler echocardiography in patients without coronary artery disease by
      angiography.
AB  - Thirty-two patients were randomly assigned to treatment with placebo or
      atorvastatin. The time-averaged peak diastolic velocity (APDV) of the left
      anterior descending artery without stenosis was measured by transthoracic Doppler
      echocardiography at rest and under hyperemic conditions before and 1 hour after
      treatment. APDV increased significantly in the atorvastatin group, at rest and
      under hyperemic conditions, and coronary flow velocity reserve also increased in
      the atorvastatin group compared with patients given placebo. Atorvastatin
      improved the blood flow velocity of the normal coronary artery <1 hour after
      administration in patients without coronary artery disease by angiography.

PMID- 15979442
TI  - Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis
      factor-alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and
      cholesterol and triglyceride levels in healthy postmenopausal women.
AB  - The associations of inflammatory markers (high-sensitivity C-reactive protein [hs
      CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha, and fibrinogen) with
      anthropometric and metabolic variables were examined in a sample of 112
      postmenopausal women not receiving hormone therapy. Body fat distribution was
      measured by computed tomography, and insulin sensitivity was determined by an
      euglycemic-hyperinsulinemic clamp. hs-CRP (0.10 < or = r(2) < or =0.37) and IL-6
      (0.06 < or = r(2) < or =0.31) were significantly associated with anthropometric
      and metabolic variables, including visceral and subcutaneous adipose tissue,
      systolic and diastolic blood pressure, triglycerides, high-density lipoprotein
      (HDL) cholesterol, and insulin sensitivity (p <0.05). Women with greater hs-CRP
      concentrations showed deterioration in their metabolic risk profiles, including
      abdominal obesity, greater triglyceride and lower HDL cholesterol concentrations,
      and lower insulin sensitivity compared with women with lower hs-CRP levels. Fifty
      nine percent of women with high hs-CRP concentrations had the metabolic syndrome
      as recently defined by the Third Report of the National Cholesterol Education
      Program Expert Panel on Detection, Evaluation, and Treatment of High Blood
      Cholesterol in Adults. After adjustment for visceral adipose tissue, most of the
      differences in the plasma lipid-lipoprotein profile were eliminated between women
      with high hs-CRP levels and women with low hs-CRP levels, whereas some
      differences in blood pressure variables, insulin sensitivity, and inflammatory
      markers (IL-6 and fibrinogen) remained significant. In conclusion, these results
      suggest that increased visceral adipose tissue levels appear to be a determinant
      covariable of the association between high hs-CRP concentrations and alteration
      in the metabolic profile.

PMID- 15979443
TI  - Effect of leisure time exercise on high-density lipoprotein cholesterol, its
      subclasses, and size in Asian Indians.
AB  - Asian Indians have a greater prevalence and incidence of coronary artery disease
      than other ethnic groups, despite similar routine lipid profiles. High-density
      lipoprotein (HDL) cholesterol, particularly the large subclass, is predominantly
      associated with coronary artery disease protection. Exercise reduces coronary
      artery disease risk by improving HDL cholesterol levels. The effect of exercise
      on HDL cholesterol concentrations, subclasses, and size, measured by nuclear
      magnetic resonance spectroscopy, was assessed in 388 healthy Asian Indians.
      Exercise was associated with significantly greater concentrations of total HDL
      cholesterol, entirely due to significant increases in the cardioprotective large
      HDL subclass and larger HDL cholesterol particle sizes.

PMID- 15979444
TI  - Association of deranged adrenal steroid metabolism with anemia in chronic heart
      failure.
AB  - The relation between adrenal steroid hormone imbalance, as quantified by the
      cortisol/dehydroepiandrosterone (DHEA) ratio, and hemoglobin concentrations was
      appraised in 92 men with stable chronic heart failure (CHF). The cortisol/DHEA
      ratio was independently and inversely associated with hemoglobin concentrations,
      suggesting that alterations of the steroid milieu may play a role in the
      pathogenesis of anemia in CHF.

PMID- 15979445
TI  - B-type natriuretic peptide and tissue Doppler study findings in elderly patients
      hospitalized for acute diastolic heart failure.
AB  - The imbalance of Starling's forces was investigated in 25 elderly patients
      hospitalized for acute diastolic heart failure. Tissue Doppler evidence of
      elevated left ventricular filling pressures was present on admission in 17
      patients with high B-type natriuretic peptide (BNP) levels. Serum proteins
      concentrations and colloid osmotic pressure, related to malnutrition and severe
      sepsis, were significantly less in the 8 patients without tissue Doppler evidence
      of elevated filling pressures, and a high level of BNP was consistent with
      paroxysmal elevation in filling pressures in this setting.

PMID- 15979446
TI  - Comparison of effectiveness of cardiac resynchronization therapy in patients with
      versus without diabetes mellitus.
AB  - The effect of long-term cardiac resynchronization therapy (CRT) was evaluated in
      32 patients with heart failure (HF) and diabetes mellitus (DM) compared with 65
      patients with HF and no DM. Clinical parameters were obtained before and after 6
      months of CRT. Long-term follow-up was performed <2 years after implantation.

PMID- 15979447
TI  - Utility of echocardiographic radial strain imaging to quantify left ventricular
      dyssynchrony and predict acute response to cardiac resynchronization therapy.
AB  - Echocardiographic strain imaging was used to quantify radial mechanical
      dyssynchrony in 38 patients who underwent cardiac resynchronization therapy.
      Dyssynchrony, defined as the time difference of peak radial strain in the septum
      versus the posterior wall, was significantly greater in patients with acute
      hemodynamic responses, and changes in radial dyssynchrony correlated with changes
      in stroke volume. A > or =130-ms difference in septal versus posterior wall peak
      strain when combined with a favorable left ventricular lead position was strongly
      predictive of immediate improvement in stroke volume with resynchronization
      therapy (95% sensitivity, 88% specificity), regardless of electrocardiographic
      QRS duration.

PMID- 15979448
TI  - Effect of enalapril on left ventricular diameters and exercise capacity in
      asymptomatic or mildly symptomatic patients with regurgitation secondary to
      mitral valve prolapse or rheumatic heart disease.
AB  - The effects of 12 months of therapy were evaluated in 47 mildly symptomatic
      patients with moderate to severe mitral valve regurgitation; 26 patients received
      enalapril and 21 received a placebo. Enalapril was associated with a significant
      reduction in left ventricular diameter and mitral regurgitation volume, with no
      evidence of change in systolic function indexes. However, enalapril did not
      hinder progressive aerobic impairment to effort.

PMID- 15979449
TI  - Electrocardiographic findings over time in arrhythmogenic right ventricular
      dysplasia/cardiomyopathy.
AB  - Thirty-five patients with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy underwent serial electrocardiographic (ECG) testing and
      were evaluated for evidence of ECG progression. Over a median of 43 months, 89%
      of the patients had evidence of progression, with S-wave prolongation being the
      most prevalent marker of ECG progression.

PMID- 15979450
TI  - Percutaneous interventional closure of large pulmonary arteriovenous fistulas
      with the amplatzer duct occluder.
AB  - Large pulmonary arteriovenous fistulas (PAVFs) are difficult for transcatheter
      treatment. This report presents 5 patients aged 3 to 73 years with large PAVFs
      who underwent successful transcatheter closure with the Amplatzer duct occluder
      (ADO), designed for the occlusion of patent duct arteriosus. The procedures were
      performed without complications and provided sustained improvement in arterial
      oxygen saturation and exercise tolerance on follow-up examination in all
      patients. The transcatheter closure of large PAVFs with the ADO is effective and
      can eliminate the need for surgical intervention. The newly designed Amplatzer
      vascular plug is undergoing clinical trials.

PMID- 15979451
TI  - A medical strategy to reduce persistent chest tube drainage after the fontan
      operation.
AB  - A standardized medical regimen aimed at reducing pleural effusions after the
      Fontan operation was compared with a randomly selected retrospective cohort. The
      duration of chest tube drainage, hospital stay, and the need for pleural
      sclerosis were significantly reduced, indicating that postoperative management
      plays an important role in reducing this morbidity.

PMID- 15979452
TI  - Fetal echocardiography and its evolving impact 1992 to 2002.
AB  - The change in frequency over a 10-year time span of establishing a prenatal
      cardiac diagnosis was studied in infants requiring cardiac surgery in the newborn
      period. The frequency of prenatal diagnosis increased from 8% to 57%, resulting
      in earlier postnatal diagnosis and a shift toward delivery in a tertiary care
      center; the most commonly prenatally diagnosed lesions were either ductal
      dependent or single ventricular in nature.

PMID- 15979453
TI  - Effect of mental stress on coronary flow velocity reserve in healthy men.
AB  - The effect of mental stress on coronary flow velocity reserve (CFVR) was examined
      in healthy men using transthoracic Doppler echocardiography. In the mental stress
      group (n = 31), CFVR was significantly reduced at 15 (to 3.3 +/- 0.8, p <0.001)
      and 30 (to 3.7 +/- 0.8, p <0.01) minutes after mental stress testing, compared
      with before mental stress (4.3 +/- 0.9), whereas it did not change in each of 3
      measurements in control subjects (n = 10). Mental stress impaired coronary
      circulation even after a certain interval after the stress.

PMID- 15979454
TI  - Usefulness of angle corrected tissue Doppler to assess segmental left ventricular
      function during dobutamine stress echocardiography in patients with and without
      coronary artery disease.
AB  - The application of angle correction to tissue Doppler (TD) during dobutamine
      stress echocardiography (DSE) extends the application of TD to all left
      ventricular segments, improves the differentiation of abnormal from normal
      segmental responses to stress, and has promise to improve its clinical utility
      for objectively evaluating wall motion during DSE.

PMID- 15979455
TI  - Effect of transdermal hormone replacement therapy on the monocyte chemoattractant
      protein-1 concentrations and other vascular inflammatory markers and on
      endothelial function in postmenopausal women.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is related to the progression of
      atherosclerosis. However, little is known about the effects of transdermal
      hormone replacement therapy (HRT) on circulating MCP-1, vascular inflammatory
      marker concentrations, and endothelial function in postmenopausal women. The
      effects of transdermal HRT on circulating MCP-1, vascular inflammatory marker
      concentrations, and endothelium-dependent vasodilation were investigated in
      postmenopausal women. Thirty-three women received transdermal HRT (continuous 17
      beta estradiol patch 36 microg/day plus cyclic oral medroxyprogesterone acetate
      2.5 mg/day for 12 days/month) for 12 months, and 27 control patients did not.
      Brachial artery flow-mediated vasodilation (FMD), assessed by ultrasound, and
      circulating MCP-1 and vascular inflammatory marker (C-reactive protein,
      intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1
      [VCAM-1], and E-selectin) concentrations were measured before and after 12 months
      of treatment. In the HRT group, MCP-1 concentrations decreased significantly (p
      <0.001), and ICAM-1, VCAM-1, and E-selectin concentrations decreased
      significantly (p <0.01 for all), but C-reactive protein concentrations did not
      change. MCP-1 and other marker concentrations did not change in the control
      group. FMD increased significantly in the HRT group (p <0.001) but did not change
      in the control group. Nitroglycerin-induced vasodilation did not change in either
      group. In conclusion, transdermal HRT decreased MCP-1 and cell adhesion molecule
      concentrations and improved endothelial function in postmenopausal women.
      Transdermal HRT may exert an antiatherosclerotic effect by improving MCP-1 and
      cell adhesion molecule expression and endothelial function.

PMID- 15979456
TI  - Franz H. Messerli, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 15979457
TI  - The ideal diet is the one indicated by evolution.

PMID- 15979458
TI  - Tumstatin, the NC1 domain of alpha3 chain of type IV collagen, is an endogenous
      inhibitor of pathological angiogenesis and suppresses tumor growth.
AB  - Angiogenesis, the formation of new blood vessels, is required for physiological
      development of vertebrates and repair of damaged tissue, but in the pathological
      setting contributes to progression of cancer. During tumor growth, angiogenesis
      is supported by up-regulation of angiogenic stimulators (pro-angiogenic) and down
      regulation of angiogenic inhibitors (anti-angiogenic). The switch to the
      angiogenic phenotype (angiogenic switch) allows the tumors to grow and facilitate
      metastasis. The bioactive NC1 domain of type IV collagen alpha3 chain, called
      tumstatin, imparts anti-tumor activity by inducing apoptosis of proliferating
      endothelial cells. Tumstatin binds to alphaVbeta3 integrin via a mechanism
      independent of the RGD-sequence recognition and inhibits cap-dependent protein
      synthesis in the proliferating endothelial cells. The physiological level of
      tumstatin is controlled by matrix metalloproteinase-9, which most effectively
      cleaves it from the basement membrane and its physiological concentration in the
      circulation keeps pathological angiogenesis and tumor growth in check. These
      findings suggest that tumstatin functions as an endogenous inhibitor of
      pathological angiogenesis and functions as a novel suppressor of proliferating
      endothelial cells and growth of tumors.

PMID- 15979459
TI  - The glycosphingolipid receptor for Vibrio trachuri in the red sea bream intestine
      is a GM4 ganglioside which contains 2-hydroxy fatty acids.
AB  - Three major glycosphingolipids (tentatively designated IGL-1, 2, and 3) were
      isolated from the intestine of red sea bream (Pagrus major) and were subjected to
      a TLC-overlay assay with (35)S-labeled Vibrio trachuri which causes vibriosis of
      fish. The bacteria adhered to IGL-2, which was determined to be a GM4 ganglioside
      (NeuAcalpha2-3Galbeta1-ceramide). The fatty acid portion of IGL-2 was composed of
      2-hydroxy C22:0, C24:0, and C24:1, in addition to the non-hydroxy C16:0 and
      C18:0, while the sphingoid base was composed exclusively of sphingenine (d18:1).
      Among glycosphingolipids tested, V. trachuri adhered to GM4 the most strongly
      followed by adherence to GM3 and GalCer, but the bacteria did not adhere to GM1a,
      GM2, LacCer, or GlcCer. V. trachuri was found to aggregate with the erythrocytes
      coated with GM4, but not with those coated with GM1a or GM2, thus indicating that
      specific adhesion occurs on intact cells. Interestingly, the dynamics for
      adhesion of V. trachuri to glycosphingolipids was defined by the structure of not
      only the sugar moiety but also the ceramide moiety, since the bacteria adhered to
      GM4 which contained 2-hydroxy fatty acids much more strongly than to that which
      contained non-hydroxy fatty acids.

PMID- 15979460
TI  - Midkine, a newly discovered regulator of the renin-angiotensin pathway in mouse
      aorta: significance of the pleiotrophin/midkine developmental gene family in
      angiotensin II signaling.
AB  - We previously demonstrated that pleiotrophin (PTN the protein, Ptn the gene)
      highly regulates the levels of expression of the genes encoding the proteins of
      the renin-angiotensin pathway in mouse aorta. We now demonstrate that the levels
      of expression of these same genes are significantly regulated in mouse aorta by
      the PTN family member midkine (MK the protein, Mk the gene); a 3-fold increase in
      expression of renin, an 82-fold increase in angiotensinogen, a 6-fold decrease in
      the angiotensin converting enzyme, and a 6.5-fold increase in the angiotensin II
      type 1 and a 9-fold increase in the angiotensin II type 2 receptor mRNAs were
      found in Mk-/- mouse aorta in comparison with the wild type (WT, +/+). The
      results in Mk-/- mice are remarkably similar to those previously reported in Ptn
      /- mouse aorta, with the single exception of that the levels of the
      angiotensinogen gene expression in Ptn-/- mice are equal to those in WT+/+ mouse
      aorta, and thus, in contrast to Mk gene expression unaffected by levels of Ptn
      gene expression. The data indicate that MK and PTN share striking but not
      complete functional redundancy. These data support potentially high levels
      importance of MK and the MK/PTN developmental gene family in downstream signals
      initiated by angiotensin II either in development or in the many pathological
      conditions in which MK expression levels are increased, such as atherosclerosis
      and many human neoplasms that acquire constitutive endogenous Mk gene expression
      by mutation during tumor progression and potentially provide a target through the
      renin-angiotensin pathway to treat advanced malignancies.

PMID- 15979461
TI  - Analysis of functional domains of rat mitochondrial Fis1, the mitochondrial
      fission-stimulating protein.
AB  - In yeast, mitochondrial-fission is regulated by the cytosolic dynamin-like GTPase
      (Dnm1p) in conjunction with a peripheral protein, Mdv1p, and a C-tail-anchored
      outer membrane protein, Fis1p. In mammals, a dynamin-related protein (Drp1) and
      Fis1 are involved in the mitochondrial-fission reaction as Dnm1 and Fis1
      orthologues, respectively. The involvement of other component(s), such as the
      Mdv1 homologue, and the mechanisms regulating mitochondrial-fission remain
      unclear. Here, we identified rat Fis1 (rFis1) and analyzed its structure-function
      relationship. Blue-native-polyacrylamide gel electrophoresis revealed that rFis1
      formed a approximately 200-kDa complex in the outer mitochondrial membrane. Its
      expression in HeLa cells promoted extensive mitochondrial fragmentation, and gene
      knock-down by RNAi induced extension of the mitochondrial networks. Taking
      advantage of these properties, we analyzed functional domains of rFis1. These
      experiments revealed that the N-terminal and C-terminal segments are both
      essential for oligomeric rFis1 interaction, and the middle TPR-like domains
      regulate proper oligomer assembly. Any mutations that disturb the proper
      oligomeric assembly compromise mitochondrial division-stimulating activity of
      rFis1.

PMID- 15979462
TI  - Refractive index distribution and optical properties of the isolated human lens
      measured using magnetic resonance imaging (MRI).
AB  - Using a non-invasive MRI technique for measuring the refractive index
      distribution through the crystalline lens, refractive index maps were obtained
      through 20 intact isolated human lenses (7-82years). Focal length measurements,
      obtained by simulated light ray propagation through each index map were found to
      be in agreement with direct measurements performed on a scanning laser apparatus.
      With increasing age, the refractive index profiles became flatter in the central
      region, accompanied by steepening of the profile in the periphery. This appears
      to be an important mechanism underlying the observed changes in power and
      longitudinal aberration of the human lens.

PMID- 15979463
TI  - Estimating chromatic contrast thresholds from the transient visual evoked
      potential.
AB  - Chromatic contrast thresholds may be estimated from transient VEPs by measuring
      the peak-to-peak amplitude at a range of stimulus levels followed by
      extrapolation to zero amplitude. However, there have been reports of failure of
      this technique when applied to the transient chromatic VEP due to variability of
      amplitude, difficulties with component identification and poor correlation of
      amplitude with stimulus level. The aim of our study was to compare methods of
      transient VEP chromatic contrast threshold estimation in terms of success rate
      and comparison with psychophysical threshold. We found each of the methods we
      investigated to have a high success rate, and in most cases VEP and
      psychophysical thresholds did not differ significantly.

PMID- 15979464
TI  - Attention modulates psychophysical and electrophysiological response to visual
      texture segmentation in humans.
AB  - To investigate whether processing underlying texture segmentation is limited when
      texture is not attended, we measured orientation discrimination accuracy and
      visual evoked potentials (VEPs) while a texture bar was cyclically alternated
      with a uniform texture, either attended or not. Orientation discrimination was
      maximum when the bar was explicitly attended, above threshold when implicitly
      attended, and fell to just chance when unattended, suggesting that orientation
      discrimination based on grouping of elements along texture boundary requires
      explicit attention. We analyzed tsVEPs (variations in VEP amplitude obtained by
      algebraic subtraction of uniform-texture from segmented-texture VEPs) elicited by
      the texture boundary orientation discrimination task. When texture was
      unattended, tsVEPs still reflected local texture segregation. We found larger
      amplitudes of early tsVEP components (N75, P100, N150, N200) when texture
      boundary was parallel to texture elements, indicating a saliency effect, perhaps
      at V1 level. This effect was modulated by attention, disappearing when the
      texture was not attended, a result indicating that attention facilitates grouping
      by collinearity in the direction of the texture boundary.

PMID- 15979465
TI  - Non-monotonic changes in performance with eccentricity modeled by multiple
      eccentricity-dependent limitations.
AB  - Eccentricity-dependent resolution losses are sometimes compensated for in
      psychophysical experiments by magnifying (scaling) stimuli at each eccentricity.
      The use of either pre-selected scaling factors or unscaled stimuli sometimes
      leads to non-monotonic changes in performance as a function of eccentricity. We
      argue that such non-monotonic changes arise when performance is limited by more
      than one type of constraint at each eccentricity. Building on current methods
      developed to investigate peripheral perception [e.g., Watson, A. B. (1987).
      Estimation of local spatial scale. Journal of the Optical Society of America A, 4
      (8), 1579-1582; Poirier, F. J. A. M., & Gurnsey, R. (2002). Two eccentricity
      dependent limitations on subjective contour discrimination. Vision Research, 42,
      227-238; Strasburger, H., Rentschler, I., & Harvey Jr., L. O. (1994). Cortical
      magnification theory fails to predict visual recognition. European Journal of
      Neuroscience, 6, 1583-1588], we show how measured scaling can deviate from a
      linear function of eccentricity in a grating acuity task [Thibos, L. N., Still,
      D. L., & Bradley, A. (1996). Characterization of spatial aliasing and contrast
      sensitivity in peripheral vision. Vision Research, 36(2), 249-258]. This
      framework can also explain the central performance drop [Kehrer, L. (1989).
      Central performance drop on perceptual segregation tasks. Spatial Vision, 4, 45
      62] and a case of "reverse scaling" of the integration window in symmetry [Tyler,
      C. W. (1999). Human symmetry detection exhibits reverse eccentricity scaling.
      Visual Neuroscience, 16, 919-922]. These cases of non-monotonic performance are
      shown to be consistent with multiple sources of resolution loss, each of which
      increases linearly with eccentricity. We conclude that most eccentricity
      research, including "oddities", can be explained by multiple-scaling theory as
      extended here, where the receptive field properties of all underlying mechanisms
      in a task increase in size with eccentricity, but not necessarily at the same
      rate.

PMID- 15979466
TI  - Detection, discrimination and integration of second-order orientation information
      in strabismic and anisometropic amblyopia.
AB  - To better understand the nature of the cortical deficit in amblyopia we undertook
      a systematic investigation of second-order processing in 8 amblyopic and 8 normal
      observers. We investigated local detection, discrimination and global
      integration. Our local stimulus consisted of a Gaussian patch of fractal noise
      multiplied by a 1-d sinusoidal modulator. Our global stimulus consisted of an
      array of such elements. We revealed second-order detection deficits for stimuli
      with equi-visible carriers. Orientation discrimination for an isolated second
      order patch was comparable in normal and amblyopic eyes. We showed that pure
      integration of second-order patterns can be normal in amblyopia.

PMID- 15979467
TI  - Glass-pattern detection is tuned for stereo-depth.
AB  - We investigated the role of disparity information in the detection of global
      form. Glass patterns, which allow insight into processing at both local and
      global stages of form analysis, were used as stimuli. We determined how detection
      of concentric Glass patterns is affected by a disparity difference introduced
      between partner dots forming local dipoles (Experiment 1), and how detection is
      affected by the addition of randomly oriented dot-pairs (noise dots) at crossed
      and uncrossed disparities (Experiment 2). The first experiment showed that
      detection thresholds increased when partner dots were separated in depth at
      disparities greater than approximately 17 min arc; the second experiment showed
      that noise dots disrupted the detection of form if they were presented at
      disparities of between approximately +/-20 min arc from the Glass pattern's
      presentation depth plane. Our findings suggest that disparity information plays a
      role in the recovery of the image structure and, importantly, local and global
      form mechanisms were found to be selective for a small range of stereo-depths. We
      discuss the findings of our study in the light of current evidence indicating
      that a common neural substrate is responsible for the analysis of form and
      binocular disparity.

PMID- 15979469
TI  - Microsurgical laryngotracheal reconstruction.
AB  - Laryngotracheal reconstruction using free-tissue transfer represents one of the
      new challenges for the head and neck reconstructive surgeon. This article reviews
      the anatomy and physiology of the larynx and trachea and discusses the clinical
      context of laryngotracheal reconstruction, particularly with regard to malignant
      tumors involving the larynx and cervical trachea. It reviews the free-tissue
      reconstructive options, including the free forearm flap, the temporoparietal
      flap, and the two-staged procedure described by Delaere.

PMID- 15979470
TI  - Double free flaps in head and neck reconstruction.
AB  - This article discusses the indications for and the advantages and principles of
      flap combinations and the selection of two pairs of recipient vessels for double
      free-flap transfers in reconstruction of extensive composite head and neck
      defects.

PMID- 15979471
TI  - Paranasal sinus and midfacial reconstruction.
AB  - Midface defects pose the most difficult of the facial reconstruction problems.
      Current reconstruction relies heavily on microsurgical techniques, among which
      there are numerous possibilities. Although midface defects frequently extend to
      the upper and lower face, often an awareness of the midface subunits most
      involved can be of critical importance. This article presents an approach that
      will help the surgeon to identify the defect-related problems, prioritize the
      reconstructive goals, and select the best surgical option in the total patient
      context.

PMID- 15979472
TI  - Through and through defects of the lower face.
AB  - This article considers the particular demands of reconstruction of this complex
      region of the head and neck in terms of its functional and aesthetic
      requirements. It presents a classification system that may assist in the
      selection of the appropriate reconstruction. Finally, the authors discuss some of
      the more common techniques and flaps that should be considered when planning
      microsurgical management, and they review the outcomes they have seen in terms of
      speech, diet tolerance, oral continence, and survival.

PMID- 15979473
TI  - Pharyngo-cervical esophageal reconstruction.
AB  - Patients with advanced-stage hypopharyngeal or cervical esophageal carcinoma have
      a poor prognosis and may require a pharyngolaryngo-cervical esophagectomy. This
      treatment is usually palliative. In the past, the localized defect after
      resection has been reconstructed using many techniques. Currently, microsurgical
      techniques have become most common, both for full and partial circumferential
      defects. The jejunal free flap is the most frequently used, with free skin flaps
      as an alternative. The surgical complication rate is acceptable. Insufficient
      quantitative data exist to document postoperative swallowing function. Speech
      rehabilitation is often done with a tracheo-esophageal puncture technique, but
      studies documenting how the various methods of surgical reconstruction affect
      speech are lacking.

PMID- 15979474
TI  - Methodologic issues in the comparison of microsurgical flaps/techniques in head
      and neck reconstruction.
AB  - This article informs head and neck microsurgeons, investigators, and readers of
      the head and neck microsurgical literature about key methodologic issues when
      comparing techniques/flaps in head and neck reconstruction. The following is
      discussed: (1) the principles of evidence-based microsurgery, (2) the hierarchy
      of the strength of evidence for treatment decisions in microsurgery, (3) types of
      questions asked (background and foreground questions) to identify the best
      available evidence, (4) strategies for searching the head and neck microsurgical
      literature, (5) issues regarding study outcomes (types, perspective, and time
      horizon) in microsurgery, (6) the relevance of incorporating economic analyses
      into head and neck microsurgical trials, and (7) the interpretation and
      applicability of published study results to an individual microsurgeon's clinical
      practice.

PMID- 15979475
TI  - Oromandibular reconstruction after cancer resection.
AB  - The goals of this article are (1) to summarize the epidemiology of oromandibular
      cancer, (2) to describe the classification of defects after cancer extirpation,
      and (3) to discuss the principles of and state of the art in reconstruction of
      the oromandibular defect. The four commonly used flaps (fibula flap, radial
      forearm flap, scapula flap, and the iliac crest) and their key characteristics
      are summarized. Finally, some future speculations are entertained.

PMID- 15979476
TI  - Scalp and forehead reconstruction.
AB  - The reconstruction of defects that involve the scalp and forehead presents unique
      aesthetic and functional challenges. This article reviews the surgical anatomy of
      these regions and presents an algorithm for decision making in reconstructive
      surgery. Nonmicrosurgical techniques are briefly reviewed. The microsurgical
      reconstruction of scalp and forehead defects differs from the more common
      oropharyngeal reconstructions in several ways, including flap choices, choices
      for recipient vessels, and the opportunity to use conventional and microsurgical
      techniques simultaneously to improve outcomes. Each of these considerations is
      reviewed and the authors' preferred techniques presented.

PMID- 15979477
TI  - Reconstruction of skull base defects.
AB  - Skull base defects are classified into three regions based on the anatomic
      location and growth pattern of the tumors. The goals of reconstruction are based
      on the necessity of obtaining a watertight seal between the cranial contents and
      the aerodigestive tract, thereby avoiding any communication, which could result
      in ascending meningitis. Pedicled flap options have largely been replaced by free
      tissue transfers, with the exception of small Zone I defects that can still be
      safely reconstructed with local pedicle flaps. The rectus abdominis free muscle
      flap has become the workhorse of skull base reconstruction, resulting in a
      decrease in the complication rate following these procedures. Various other
      factors have significantly improved the prognosis of patients who require tumor
      ablation involving the skull base.

PMID- 15979478
TI  - Allotransplantation of the face: how close are we?
AB  - Reconstruction of patients with severe facial disfigurements due to burns,
      trauma, or cancer is a challenging task for plastic surgeons. Currently,
      available reconstructive options rarely result in satisfactory functional and
      aesthetic outcomes. In this article the authors present the rationale and
      experimental basis for the introduction of composite facial allograft
      transplantation in humans. They outline the ethical, social, and media-related
      issues in facial allograft transplantation.

PMID- 15979479
TI  - Reconstruction for total and near-total glossectomy defects.
AB  - Reconstruction of total or near-total glossectomy defects has been challenging
      and the functional outcomes are often disappointing. In this article, the 10-year
      experience of total or near-total tongue reconstruction at the University of
      Texas M.D. Anderson Cancer Center is reviewed. The trends of surgical and
      functional outcomes, length of hospital stay, and choices of flaps and recipient
      vessels are identified. In addition, the investigators' experience, as well as a
      literature review, of sensory and motor reinnervation for tongue reconstruction
      is presented.

PMID- 15979480
TI  - Microsurgical workhorse flaps in head and neck reconstruction.
AB  - The aim of reconstruction after resection of head and neck tumors is to achieve
      acceptable functional and esthetic results with minimal donor site morbidity.
      Although many flaps have been developed for bone and soft tissue reconstructions,
      our experience in the past years has identified the anterolateral thigh flap
      (cutaneous or myocutaneous), the radial forearm flap, and the osteoseptocutaneous
      fibula flap as the most useful flaps for head and neck reconstruction. These
      three flaps can be used for reconstruction of almost all kinds of defects, either
      as a single flap or in combination. The harvest of these flaps is relatively
      simple and straightforward. All flaps have adequate pedicle vessel length and
      caliber. Donor site morbidity is negligible. As most reconstructive microsurgeons
      do not have enough patient volume to master many different kinds of flaps in
      their professional life, we recommend focusing on these three flaps as workhorse
      flaps instead of hunting for many other flaps for head and neck reconstruction.

PMID- 15979481
TI  - Lip and perioral reconstruction.
AB  - For defects up to approximately 80% of either upper or lower lip, reconstructions
      that use remaining lip and cheek can function and look reasonably well. Free
      tissue transfers, such as the free radial forearm flap, are useful for larger
      defects as they import additional tissue in one step and reduce microstomia,
      which is more likely to result from local tissue repairs. At best, free flaps
      provide a static dam or curtain that functions as a lip; at worst, they deliver a
      large amount of composite tissue to allow for primary healing. Satisfactory
      outcomes after free flap reconstructions for lip are best achieved when the
      transferred tissue is integrated with the native tissues by suspending free flaps
      appropriately, resurfacing with the flaps with vermilion substitutes, and
      judicious interposition of remaining lip segments.

PMID- 15979483
TI  - Histoplasma endocarditis: clinical and mycologic features and outcomes.
AB  - OBJECTIVES: To define the salient clinical and microbiologic characteristics and
      outcome of infective endocarditis caused by Histoplasma capsulatum. METHODS: Case
      report and review of 43 literature cases. RESULTS: Infection involved both native
      (36 cases) and prosthetic (7) heart valves, had a high rate of systemic
      embolization (58%), and a more delayed diagnosis than bacterial endocarditis.
      Cardiac involvement generally occurred on mitral and/or aortic valves, and almost
      always in the setting of disseminated disease. Antemortem diagnosis was best made
      by serology (serum antibody titers or urinary antigen) or culture of blood
      (positive in <20% of cases), bone marrow, excised valves, and other non-blood
      specimens. Other diagnostic methods included histopathology and immunofluorescent
      staining of tissue samples. Untreated infection was uniformly fatal. Prolonged
      antifungal therapy with amphotericin B, without surgical intervention, appeared
      more effective than for Candida endocarditis. CONCLUSIONS: Histoplasma
      endocarditis is an infrequent but important cause of left-sided, blood culture
      negative endocarditis. Its true prevalence may be underestimated because of the
      relative difficulty in making a precise microbiologic diagnosis. Amphotericin B
      therapy appears more effective than for Candida endocarditis, while the role for
      azole treatment and secondary prophylaxis remains uncertain. Indications for
      surgical valve replacement are similar to those for bacterial endocarditis.

PMID- 15979484
TI  - Comparative analysis of pathogenicity of Cryptococcus neoformans serotypes A, D
      and AD in murine cryptococcosis.
AB  - OBJECTIVES: To characterize the pathogenicity of 15 strains of Cryptococcus
      neoformans belonging to several serotype/mating type allele patterns (Dalpha, Da,
      A(alpha), A(a), A(alpha)/D(a) and D(alpha)/A(a)) in experimental models of murine
      cryptococcosis. METHODS: CD1-infected mice were examined for survival and fungal
      loads in either brain or lung during the course of infection. RESULTS: All
      strains, with the exception of one Da strain, produced melanin in vitro.
      Similarly, all strains were encapsulated and produced phospholipase. When CD1
      mice were challenged intravenously (i.v.) with 5x10(5)CFU/mouse and observed for
      60 days post-infection, a significant variation of mortality rate was observed
      among mice infected with different strains. A(alpha) and A(alpha)/D(a) strains
      all produced 100% mortality within the study period with mean survivals
      significantly shorter than those of mice infected with strains belonging to any
      other allele type (P<0.0001). A wide range of pathogenicity was shown by haploid
      and diploid strains presenting D(alpha) allele. This finding was confirmed by an
      intranasal model of challenge. To investigate the progression of infection, the
      mice were challenged i.v. with 5x10(4)CFU/mouse and tissue burden experiments
      (brain and lung) were performed on days 6 and 12 post-infection. Only the mice
      infected with A(alpha) and A(alpha)/D(a) strains showed a >1 log(10) increase of
      CFU/g in both tissues throughout the study period. CONCLUSIONS: Our results
      suggest that the presence of the A(alpha) mating type allele in either haploid or
      diploid strains is correlated with virulence, while the presence of the A(a) or
      D(a) allele in haploid strains is associated with moderate or no virulence.
      Finally, either haploid or diploid strains presenting D(alpha) allele vary in
      virulence.

PMID- 15979485
TI  - Candida spondylodiscitis and epidural abscess: management with shorter courses of
      anti-fungal therapy in combination with surgical debridement.
AB  - Epidural abscess associated with candidal spondylodiscitis is rarely seen,
      particularly when it involves the cervical and thoracic spine. We report two such
      cases that were successfully managed with early surgical debridement, as well as
      medical therapy with intravenous amphotericin followed by oral fluconazole. The
      literature related to candidal spinal infection is reviewed, and a rational
      approach to the management of this uncommon condition is proposed. A good outcome
      may generally be expected with early diagnosis as well as appropriate surgical
      and pharmacological treatment. Oral fluconazole appears to be useful in the
      management of candida spondylodiscitis complicated by epidural abscess formation.
      Treatment until a normal ESR is attained is ideal, and this may be as short as 3
      months when surgical drainage has been adequately performed.

PMID- 15979486
TI  - Low rate of occult hepatitis B virus infection among anti-HBc positive blood
      donors living in a low prevalence region in Brazil.
AB  - OBJECTIVE: The aim of this study was to determine the rate of occult hepatitis B
      virus (HBV) infection among blood donors living in a geographic region of low
      (5.6%) anti-HBc prevalence. SUBJECTS AND METHODS: Sera from 150 candidate blood
      donors whose blood was rejected due to total anti-HBc reactivity (despite absence
      of HBsAg) were tested for anti-HBs and IgM anti-HBc antibodies, as well as for
      HBeAg/anti-HBe. Serum HBV DNA was sought by using a PCR assay able to amplify
      part of the surface gene. Viral load was measured in the PCR positive samples.
      RESULTS: The pattern 'anti-HBc alone' (without HBsAg and anti-HBs antibodies) was
      found in 64 (42.7%) subjects. IgM anti-HBc and anti-HBe antibodies were detected
      in 2 (1.3%) and 80 (53.3%) samples, respectively. No sample was HBeAg-reactive.
      HBV DNA was repeatedly found in five (3.3%) samples, three of which were anti-HBs
      positive and two anti-HBs negative. All five HBV DNA positive samples showed a
      low viral load (<1000copies/ml). CONCLUSIONS: The data indicated a low rate of
      occult infection among anti-HBc positive, HBsAg negative blood donors living in a
      region of low prevalence of infection. Viral load was very low in all HBV
      infected subjects.

PMID- 15979487
TI  - The prevalence of SEN virus infection in blood donors in Taiwan.
AB  - OBJECTIVES: To determine the prevalence of SENV infections among blood donors in
      central Taiwan and to clarify the relationship between these infections and
      elevated alanine aminotransaminase (ALT) values. METHODS: DNA was extracted from
      plasma of 200 blood donors and amplified by seminested PCR. RESULTS: For all
      donors, the prevalence of SENV-D was 32%, and of SENV-H was 30.5%. Prevalence of
      mixed SENV-D/H infection was 11.5% and of SENV-D and/or SENV-H (SENV-D/H) was
      51%. Infections were not associated with age, gender, or raised ALT values.
      CONCLUSIONS: SENV-D and SENV-H infections are common among blood donors in
      central Taiwan but are unlikely to contribute to abnormal ALT values.

PMID- 15979488
TI  - Serum copper and zinc concentrations in patients with chronic hepatitis C.
AB  - The aim of this study was to measure the alterations in serum trace elements,
      including zinc and copper in patients with chronic hepatitis C and to compare
      them with the results of healthy individuals. Seventeen patients with chronic
      hepatitis C and 17 healthy individuals were included in this study. Serum zinc
      and cooper concentrations were measured by using atomic absorption
      spectrophotometer of patients with chronic hepatitis C and the results were
      statistically compared with those of healthy individuals. Serum zinc
      concentrations were 105.6+/-22.8 microg/dl in patients with chronic hepatitis C
      and 94.41+/-19 microg/dl in healthy controls, respectively. Serum copper
      concentrations were 103.17+/-20.8 microg/dl in patients with chronic hepatitis C
      and 90.8+/-14.3 microg/dl in healthy subjects, respectively. Serum zinc and
      copper concentrations were not found statistically different in patients with
      chronic hepatitis C compared with those of healthy individuals (p>0.05). In
      conclusion, serum trace element concentrations did not show statistical
      alterations in patients with chronic hepatitis C compared to healthy subjects.

PMID- 15979489
TI  - Serum copper and zinc concentrations in patients with chronic hepatitis B.
AB  - The aim of this study was to measure the alterations in serum trace elements,
      including zinc and copper in patients with chronic hepatitis and to compare with
      the results of healthy individuals. The serum zinc and copper concentrations were
      measured by using atomic absorption spectrophotometer in sera of patients with
      chronic hepatitis and statistically compared with those of healthy individuals.
      One hundred and five subjects, 71 patients with chronic hepatitis B (46
      asymptomatic carriers, 25 chronic active hepatitis B) and 34 healthy individuals
      were included in this study. Sera of patients with chronic hepatitis and
      statistically compared with those of healthy individuals. Serum zinc
      concentrations were 104+/-24.98 microg/dl in asymptomatic carriers, 97+/-16.03
      microg/dl in chronic active hepatitis and 108+/-21.07 in healthy controls,
      respectively. Serum copper concentrations were 88+/-17.8 microg/dl in
      asymptomatic carriers, 86+/-20.02 microg/dl in patients with chronic active
      hepatitis B and 88+/-13.59 microg/dl in healthy controls, respectively. Serum
      zinc and copper concentrations were not statistically different in patients with
      chronic hepatitis B compared with those of healthy individuals (p>0.05). Serum
      trace element concentrations did not show statistical alterations in patients
      with chronic hepatitis B compared with healthy subjects.

PMID- 15979490
TI  - Validity of existing CD4+ classification in north Indians, in predicting immune
      status.
AB  - BACKGROUND: The CD4 lymphocyte count had ethnic variability as observed in many
      studies. In populations with CD4 counts inherently lower than in the West, the
      Center for Disease Control and Prevention (CDC) classification system of HIV
      infected individuals may not be appropriate. As there is no such criterion
      currently available for ethnic north Indians HIV-patients, we undertook this
      study to assess the applicability of the western case definition in north Indian
      HIV patients. METHODS: The CD4 counts of 40 normal and 376 HIV-infected north
      Indian adults attending to ID clinic, SS hospital, Varanasi were estimated by
      flowcytometry. The mean CD4 counts were estimated and compared between CDC groups
      A, B and C and controls. Receiver operator characteristic (ROC) curves were
      generated to determine the cut-off that correlated best with clinical staging for
      this population. RESULTS: For CDC groups A, B and C, the mean CD4 counts/mul
      (upper limits of the 95% CI) were 380.3, 249.2 and 120.9, while the mean CD4
      levels in healthy volunteers was 818.4. CONCLUSION: The mean CD4 count among
      normal north Indians is significantly lower than that in the western population
      and parallels that of the Chinese. When categorized based on the Center for
      Disease Control and Prevention (CDC) classification system, the mean CD4 counts
      in HIV-infected individuals was lower. Categories of CD4 counts >280, 120-280 and
      < or =120 cells/microl correlate better with disease progression among HIV
      infected individuals. A longitudinal study is required before guidelines for the
      India population can be devised.

PMID- 15979491
TI  - Role of nitric oxide (NO) in interferon-alpha therapy for hepatitis C.
AB  - BACKGROUND AND AIM: The role of nitric oxide in infectious disease is gaining
      increased attention because antiviral effects of nitric oxide. In addition, there
      is evidence that nitric oxide synthase-2 expression was noted in chronic
      hepatitis C found within mononuclear cells. METHODS: We studied serum levels of
      nitrite and nitrate before and during interferon alpha therapy in 66 patients
      with chronic hepatitis C. RESULTS: There was no significant difference of their
      levels between the healthy control subjects and the patients before the treatment
      with interferon (55.9+/-21.8 microM vs. 60.9+/-30.0 microM). Their levels were
      determined at 2 weeks after the initiation of treatment with interferon and
      compared with those before the treatment in the patients with chronic hepatitis
      C. In the total patients treated, there was no significant difference between
      their levels before and at 2 weeks after the treatment (60.9+/-30.0 microM vs.
      65.5+/-30.0 microM, P=0.14). However, when the levels were compared between
      sustained responders, in whom hepatitis C virus was eradicated, and non
      responders, in whom the virus was not eradicated, the former had significantly
      higher levels of nitrite and nitrate than the latter at 2 weeks after the
      initiation of treatment (83.7+/-40.9 microM vs. 57.6+/-19.5 microM, P<0.01). The
      multivariate logistic regression analysis showed that the rise of nitrite and
      nitrate was an independent predictive factor for efficacy of interferon
      treatment. CONCLUSIONS: Nitric oxide may be an important factor for antiviral
      therapy by interferon treatment for chronic hepatitis C, which suggests an
      additional therapeutic pathway for further study.

PMID- 15979492
TI  - Mycoplasma hominis and Ureaplasma urealyticum in patients with sterile pyuria.
AB  - OBJECTIVES: Mycoplasma hominis and Ureaplasma urealyticum are associated with
      various diseases of the urogenital tract, but they are usually not detected by
      routine microbiological diagnosis. The aim of this study was to asses the
      prevalence of these organisms in patients with sterile pyuria. METHODS: From
      December 2000 to June 2001 all urine samples sent in to microbiological
      diagnosis, which yielded > or =500 leucocytes/ml and <10(4) bacteria/ml, were
      collected for this study. Thirty-three samples from 30 patients (female: 21,
      male: nine; median age: 60 years, range: 23-91 years) met these criteria and were
      subjected to PCR for detection of M. hominis and U. urealyticum, respectively.
      RESULTS: M. hominis and U. urealyticum were detected in 2 (7%) and 6 samples
      (20%), respectively. With regard to the underlying diseases of the patients,
      glomerulonephritis was significantly associated with the detection of urogenital
      mycoplasmas (p=0.02). CONCLUSION: The prevalence of M. hominis and U. urealyticum
      found in this study corresponds to the expected prevalence in the general
      population. This finding does not indicate an association of sterile pyuria with
      urogenital mycoplasma infection/colonization.

PMID- 15979493
TI  - Effect of confounding in the association between circumcision status and urinary
      tract infection.
AB  - OBJECTIVES: To estimate the impact of confounding in the association between
      circumcision status and urinary tract infection from epidemiological factors,
      sample collection, and health-seeking behaviors in the first year of life.
      METHODS: Beginning with the assumption that true urinary tract infection occurred
      equally regardless of circumcision status, a Markov model incorporating the
      differences in the rates of prematurity, of urine collection, of false positive
      urine specimens, and of health-seeking behaviors in infant boys based on
      circumcision status was developed. Using this model, the rates of false-positive
      urine cultures, asymptomatic bacteriuria, and true urinary tract infection
      detected in the first year of life were estimated and contrasted. Error of the
      model was estimated using Monte Carlo simulations. RESULTS: Keeping the incidence
      of true urinary tract infection constant between groups, the factors included in
      the model could account for urinary tract infection being diagnosed 4.27 times
      more frequently in non-circumcised males under a year of age. CONCLUSIONS:
      Previously reported differences in the rate of urinary tract infection by
      circumcision status could be entirely due to sampling and selection bias. Until
      clinical studies adequately control for sources of bias, circumcision should not
      be recommended as a preventive for urinary tract infection.

PMID- 15979494
TI  - Community-acquired bacteraemic pneumococcal pneumonia in adults: effect of
      diminished penicillin susceptibility on clinical outcome.
AB  - Pneumococcal pneumonia remains a common disease with a high mortality rate.
      Between 1995 and 2000, we prospectively analyzed 95 consecutive adult cases of
      community-acquired bacteraemic pneumococcal pneumonia treated in a single centre.
      The incidence of pneumococcal resistance to penicillin increased from 19 to 50%
      during the study period. Multivariate analysis showed that only age and recent
      hospitalization were independently associated with fatal outcome. The proportion
      of penicillin-resistant strains was slightly but not significantly higher among
      patients who died before the fourth hospital day than among those who died later.
      Patients who died before D4 were more likely to have a recent history of
      hospitalization, cancer and/or chemotherapy. It thus appears that infection by a
      resistant pneumococcal strain is not in itself a gravity factor in this setting,
      but that their acquisition is associated with pejorative clinical features.

PMID- 15979495
TI  - Successful medical treatment of intracranial abscess caused by Brucella spp.
AB  - An unusual presentation of unilateral cerebellar abscesses due to
      neurobrucellosis observed in a patient is reported. He gave a history of fever,
      headache, vomiting and had unilateral cerebellar signs. The abscess was detected
      on magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid revealed
      neurobrucellosis. Patient treated by only antibiotics therapy, evolving to
      complete clinical and radiological resolution, without neurosurgical
      intervention. We are presenting a case of cerebellar abscess due to
      neurobrucellosis diagnosed by MRI, treated medically, and had both radiologic and
      clinical follow-up. We also made a review of the literature concerning the
      cerebellar abscess due to neurobrucellosis.

PMID- 15979496
TI  - Bacteraemia due to Pseudomonas putida and other Pseudomonas non-aeruginosa in
      children.

PMID- 15979497
TI  - Herod the Great and his worms.

PMID- 15979498
TI  - Self-administering cannabinoids.
AB  - Endocannabinoids, which are typically released by principal cells in response to
      prolonged depolarization, act as retrograde messengers to inhibit synaptic
      transmission. A recent study shows that in a specific subtype of cortical
      interneuron, endocannabinoids released under similar circumstances can also act
      cell-autonomously. Here, endocannabinoids endow these neurons with a memory of
      their own activity in the form of a long-term change in excitability.

PMID- 15979499
TI  - Why doesn't nicotinic ACh receptor immunoreactivity knock out?
AB  - Immunochemical analyses of protein expression and localization rely on the
      specificity of primary immunoreagents. A recent report, using transgenic mice,
      casts doubt on the specificity of three antibodies commonly used to
      immunolocalize alpha7 nicotinic ACh receptors. These data highlight the conundrum
      facing histologists--how 'real' is the labelling they see?

PMID- 15979500
TI  - Response to Alberini: right answer, wrong question.

PMID- 15979501
TI  - Desensitization of nicotinic ACh receptors: shaping cholinergic signaling.
AB  - Nicotinic ACh receptors (nAChRs) can undergo desensitization, a reversible
      reduction in response during sustained agonist application. Although the
      mechanism of desensitization remains incompletely understood, recent
      investigations have elucidated new properties underlying desensitization,
      indicating that it might be important to control synaptic efficacy, responses to
      cholinergic agents, and certain nAChR-related disease states. Thus, studying how
      different nAChR subunits contribute to desensitization might help to explain
      variations in responsiveness to drugs, and might thus improve their therapeutic
      applications. Agonist-specific desensitization, desensitization arising from
      resting receptors, natural mutations dramatically altering desensitization, and
      the possibility that recovery from desensitization is an important process for
      modulating receptor function, together provide a new framework for considering
      desensitization as a target to shape cholinergic signaling.

PMID- 15979503
TI  - COPII and exit from the endoplasmic reticulum.
AB  - First discovered by genetic analysis of yeast secretion mutants, the
      evolutionarily conserved vesicular coat protein II (COPII) complex is responsible
      for membrane transport from the endoplasmic reticulum (ER) to the Golgi
      apparatus. In recent years, extensive efforts in structural, morphological,
      genetic and molecular analysis have greatly enhanced our understanding of the
      structural and molecular basis of COPII subunit assembly and selective cargo
      packaging during ER export. Very recent data have also indicated that a more
      "classical" picture of vesicle formation from ER exit sites (ERES) followed by
      their transport to the Golgi is far from accurate. Proteins modulating the
      function of COPII have also emerged in recent analysis. They either affect COPII
      based cargo selection, the formation of vesicle/transport carrier, or subsequent
      targeting of the transport carrier. Together, elucidation of COPII-mediated ER
      export has painted a fascinating picture of molecular complexity for an essential
      process in all eukaryotic cells.

PMID- 15979504
TI  - ER-to-Golgi transport: form and formation of vesicular and tubular carriers.
AB  - The transport of proteins and lipids between the endoplasmic reticulum and Golgi
      apparatus is initiated by the collection of secretory cargo from within the lumen
      of the endoplasmic reticulum. Subsequently, transport carriers are formed that
      bud from this membrane and are transported to, and subsequently merge with, the
      Golgi. The principle driving force behind the budding process is the multi
      subunit coat protein complex, COPII. A considerable amount of information is now
      available regarding the molecular mechanisms by which COPII components operate
      together to drive cargo selection and transport carrier formation. In contrast,
      the precise nature of the transport carriers formed is still a matter of
      considerable debate. Vesicular and tubular carriers have been characterized that
      are, or in other cases are not, coated with the COPII complex. Here, we seek to
      integrate much of the data surrounding this topic and try to understand the
      mechanisms by which vesicular and/or tubular carriers might be generated.

PMID- 15979505
TI  - Golgi tethering factors.
AB  - Transport of cargo to, through and from the Golgi complex is mediated by
      vesicular carriers and transient tubular connections. In this review, we describe
      vesicle tethering events with the understanding that similar events occur during
      transport via larger structures. Tethering factors can be generally divided into
      a group of coiled-coil proteins and a group of multi-subunit complexes. Current
      evidence suggests that these factors function in a variety of membrane-membrane
      tethering events at the Golgi complex, interact with SNARE molecules, and are
      regulated by small GTPases of the Rab and Arl families.

PMID- 15979506
TI  - Intra-Golgi transport: a way to a new paradigm?
AB  - The morpho-functional principles of intra-Golgi transport are, surprisingly,
      still not clear, which is in marked contrast to our advanced knowledge of the
      underlying molecular machineries. Recently, the conceptual and technological
      hindrances that had delayed progress in this area have been disappearing, and a
      cluster of powerful morphological techniques has been revealing new glimpses of
      the organization of traffic in intact cells. Here, we discuss the new concepts
      around the present models of intra-Golgi transport.

PMID- 15979507
TI  - Multiple activities for Arf1 at the Golgi complex.
AB  - The Arf family of GTPases regulates membrane traffic and organelle structure. At
      the Golgi complex, Arf proteins facilitate membrane recruitment of many
      cytoplasmic coat proteins to allow sorting of membrane proteins for transport,
      stimulate the activity of enzymes that modulate the lipid composition of the
      Golgi, and assemble a cytoskeletal scaffold on the Golgi. Arf1 is the Arf family
      member most closely studied for its function at the Golgi complex. A number of
      regulators that activate and inactivate Arf1 on the Golgi have been described
      that localize to different regions of the organelle. This spatial distribution of
      Arf regulators may facilitate the recruitment of the coat proteins and other Arf
      effectors to different regions of the Golgi complex.

PMID- 15979508
TI  - Golgins and GTPases, giving identity and structure to the Golgi apparatus.
AB  - In this review we will focus on the recent advances in how coiled-coil proteins
      of the golgin family give identity and structure to the Golgi apparatus in animal
      cells. A number of recent studies reveal a common theme for the targeting of
      golgins containing the ARL-binding GRIP domain, and the related ARF-binding GRAB
      domain. Similarly, other golgins such as the vesicle tethering factor p115 and
      Bicaudal-D are targeted by the Rab GTPases, Rab1 and Rab6, respectively. Together
      golgins and their regulatory GTPases form a complex network, commonly known as
      the Golgi matrix, which organizes Golgi membranes and regulates membrane
      trafficking.

PMID- 15979509
TI  - The role of the phosphoinositides at the Golgi complex.
AB  - The phosphorylated derivatives of phosphatidylinositol (PtdIns), known as the
      polyphosphoinositides (PIs), represent key membrane-localized signals in the
      regulation of fundamental cell processes, such as membrane traffic and
      cytoskeleton remodelling. The reversible production of the PIs is catalyzed
      through the combined activities of a number of specific phosphoinositide
      phosphatases and kinases that can either act separately or in concert on all the
      possible combinations of the 3, 4, and 5 positions of the inositol ring. So far,
      seven distinct PI species have been identified in mammalian cells and named
      according to their site(s) of phosphorylation: PtdIns 3-phosphate (PI3P); PtdIns
      4-phosphate (PI4P); PtdIns 5-phosphate (PI5P); PtdIns 3,4-bisphosphate (PI3,4P2);
      PtdIns 4,5-bisphosphate (PI4,5P2); PtdIns 3,5-bisphosphate (PI3,5P2); and PtdIns
      3,4,5-trisphosphate (PI3,4,5P3). Over the last decade, accumulating evidence has
      indicated that the different PIs serve not only as intermediates in the synthesis
      of the higher phosphorylated phosphoinositides, but also as regulators of
      different protein targets in their own right. These regulatory actions are
      mediated through the direct binding of their protein targets. In this way, the
      PIs can control the subcellular localization and activation of their various
      effectors, and thus execute a variety of cellular responses. To exert these
      functions, the metabolism of the PIs has to be finely regulated both in time and
      space, and this is achieved by controlling the subcellular distribution,
      regulation, and activation states of the enzymes involved in their synthesis and
      removal (kinases and phosphatases). These exist in many different isoforms, each
      of which appears to have a distinctive intracellular localization and regulation.
      As a consequence of this subcompartimentalized PI metabolism, a sort of "PI
      fingerprint" of each cell membrane compartment is generated. When combined with
      the targeted recruitment of their protein effectors and the different
      intracellular distributions of other lipids and regulatory proteins (such as
      small GTPases), these factors can maintain and determine the identity of the cell
      organelles despite the extensive membrane flux []. Here, we provide an overview
      of the regulation and roles of different phosphoinositide kinases and
      phosphatases and their lipid products at the Golgi complex.

PMID- 15979510
TI  - Golgi structure in stress sensing and apoptosis.
AB  - The Golgi complex in mammalian cells is composed of polarized stacks of flattened
      cisternal membranes. Stacks are connected by tubules forming a reticular network
      of membranes closely associated with the microtubule-organizing center. While the
      Golgi structure is important for the efficient processing of secretory cargo, the
      organization of the mammalian Golgi complex may indicate potential functions in
      addition to the processing and sorting of cargo. Similar to the endoplasmic
      reticulum stress response pathway, the Golgi complex may initiate signaling
      pathways to alleviate stress, and if irreparable, trigger apoptosis. Here, we
      review recent experimental evidence suggesting that the elaborate structure of
      the Golgi complex in mammalian cells may have evolved to sense and transduce
      stress signals.

PMID- 15979512
TI  - Oral anatomy of the dog and cat in veterinary dentistry practice.
AB  - The study of anatomy is important to accomplish any kind of surgical and medical
      procedure and to understand the physiology and diseases of animals. It is no
      different in veterinary dentistry. The study of oral anatomy helps the
      veterinarian to accomplish any kind of surgical procedure more quickly and with
      less damage to tissues, especially in cases of major oral surgery. In fact, under
      standing the anatomy is easier when this knowledge is acquired directly, with
      surgical application. This article describes the essentials of the oral anatomy
      of the dog and cat, correlating this knowledge with the dental procedures to be
      used by veterinarians as a guide.

PMID- 15979513
TI  - The gold standard of veterinary oral health care.
AB  - Veterinary dentistry has evolved to the point that consumers now demand and
      expect the best oral health care possible for their pets. The gold standard is an
      attainable goal for all veterinary practices that provide oral health care. If
      the practice chooses to improve its delivery system, the changes should be
      rewarding.

PMID- 15979514
TI  - Juvenile veterinary dentistry.
AB  - The good news is that most dogs and cats live through their first year of life
      with no dental or oral problems requiring attention. For the others, being aware
      of the potential problems, recognizing them early, and instituting appropriate
      care in a timely manner can improve the quality of life immediately and avoid
      more serious problems in the long term.

PMID- 15979515
TI  - Management of periodontal disease: understanding the options.
AB  - Periodontal disease is the most common disease occurring in domestic dogs and
      cats, and local severity and the impact on the rest of the body are reasons why
      all companion animal patients should receive an oral examination every time they
      are seen. This article provides the background information on how an effective
      periodontal management program can be tailored for each patient.

PMID- 15979516
TI  - Fundamentals of endodontics.
AB  - Endodontic disease is a highly prevalent (>10% of all dogs) and insidiously
      painful process that can have significant local and systemic effects. The root
      canal system is a delicate organ and is prone to inflammation, infection, and
      partial and complete necrosis. Vital pulp therapy must be performed quickly,
      gently, and meticulously if it is to be effective. The relatively high rate of
      failure in direct pulp capping makes regular follow-up radiographs of critical
      importance to ensure patient health. Once a tooth is dead, there are often no
      obvious clinical signs; therefore, clinicians must be educated in the diagnosis
      of the disease processes. Once properly educated, the practitioner must remain
      vigilant for subtle signs of the disease process. Standard root canal therapy is
      an effective method of removing the inflammation, infection, and associated
      discomfort of the endodontically diseased tooth while maintaining its function.
      Endodontic failure most likely remains hidden unless dental radiology is used.
      Follow-up radiographs at regular intervals throughout the patient's life are
      critical for ensuring the long-term success of any endodontic therapy.

PMID- 15979517
TI  - Fundamentals of small animal orthodontics.
AB  - The basic principles and concepts that govern the discipline of orthodontics are
      explored. The movement of teeth is mediated primarily through the periodontal
      ligament. When the periodontal ligament is stretched, bone apposition occurs.
      Conversely, in areas of compression, bone resorption occurs. The subject tooth
      moves in the direction of the force. The orthodontist must be cognizant of the
      prevailing ethical guidelines and the functional needs of the patient.

PMID- 15979518
TI  - Gingivostomatitis.
AB  - Gingivostomatitis (GS) with various patterns of disease may require antiviral
      therapy, steroids, laser fulguration, immunomodulation drugs, or nonsteroidal
      anti-inflammatory drugs. The use of cyclosporine as an immunomodulation drug has
      long-term benefits in reduction of the immunologic events that contribute to GS.
      Whole-mouth extraction or partial extraction (premolars and molars), with
      radiographic conformation that all root remnants have been removed, may be the
      most viable option in nonresponsive and or intractably painful stomatitis in
      noncompliant cats or dogs. Oral inflammation subsided after extraction without
      the need for further medication in approximately 70% of the cats from two studies
      with previous chronic unrelenting oral disease. The combination of
      immunomodulation with cyclosporine together with laser resection of proliferative
      tissue should be recommended if extraction of teeth is not desired. Removal of
      proliferative oral tissues by lasing (carbon dioxide laser) removes the tissue
      that maybe producing tissue antigens and the area where bacteria are sequestered.
      The use of anti-inflammatory medications is recommended in the management of GS.
      Therapeutic success is achieved when there is elimination of proliferative tissue
      and inflammation.

PMID- 15979519
TI  - Update on the etiology of tooth resorption in domestic cats.
AB  - Based on recent findings of increased vitamin D activity in cats with feline
      odontoclastic resorptive lesions (FORL), the present article provides further
      clues on the possible etiology of FORL. Microscopic features of FORL and other
      peculiarities of feline permanent teeth are compared with pathologic findings
      obtained from experimental studies in other species. Administration of excess
      vitamin D or vitamin D metabolites in laboratory animals caused changes to dental
      and periodontal tissues that resemble histopathologic features of teeth from cats
      with FORL. Chronic excess dietary vitamin D may be the long-sought cause of
      multiple tooth resorption in domestic cats. It may also provide a basis for
      future research on idiopathic hypercalcemia and renal disease in the same
      species.

PMID- 15979520
TI  - Radiographic evaluation and treatment of feline dental resorptive lesions.
AB  - Many feline resorptive lesions are easily diagnosed by clinical oral examination,
      whereas others require dental radiographs. Radiographs can reveal the presence of
      resorption, and often the nature of the resorptive process as well. Removal of
      affected teeth when they cause discomfort, or of the portion of the tooth causing
      the discomfort, remains the only treatment that provides long-term resolution.
      Until we understand the etiology of the inciting causes and of the factors
      contributing to the progression of resorptive lesions, reliable prevention cannot
      be offered.

PMID- 15979521
TI  - Simple and surgical exodontia.
AB  - Preemptive and postoperative pain management is part of patient care when
      performing extractions. Simple extractions can become complicated when tooth
      roots are fractured. Adequate lighting,magnification, and surgical techniques are
      important when per-forming surgical (complicated) extractions. Radiographs should
      be taken before extractions and also during the procedure to assist with
      difficult extractions. Adequate flap design and bone removal are necessary when
      performing surgical extractions. Complications, including ocular trauma, jaw
      fracture, and soft tissue trauma, are avoided or minimized with proper patient
      selection and technique.

PMID- 15979522
TI  - Maxillofacial fracture repairs.
AB  - Oral trauma remains a common presentation in a small animal practice. Most
      fractures are the result of vehicular accidents. Among other causes are falls,
      kicks, gunshots wounds, and encounters with various hard objects ranging from
      baseball bats and golf clubs to horse hooves and car doors. Next in popularity
      are dog fights, especially when a large dog and a small dog are involved, and
      fights with other animals. With cats, falls from various heights are responsible
      for a large percentage of presentations.

PMID- 15979523
TI  - Mandibulectomy and maxillectomy.
AB  - In an animal presented for evaluation of an oral tumor, the extent of the disease
      is based on the systematic evaluation of the tumor, including diagnostic imaging,
      and the assessment of regional lymph node involvement and distant metastases. The
      nature of the disease is determined by an incisional biopsy and histopathologic
      examination. The choice of treatment and expected outcome are based on the stage
      and expected biologic behavior, which is well known for many oral tumor types.
      The various mandibulectomy and maxillectomy techniques have been shown to give
      good functional and cosmetic results.

PMID- 15979524
TI  - Regional anesthesia and analgesia for oral and dental procedures.
AB  - Regional anesthesia and analgesia benefit the client, the patient, and the
      practitioner, and their use is becoming the standard for care. Familiarity with
      the processes involved in the generation of pain aids in understanding the
      benefits of preemptive and multimodal analgesia. Local anesthetic blocks should
      be a key component of a treatment plan, along with opioids, nonsteroidal anti
      inflammatory drugs, N-methyl-D-aspartate receptor antagonists, and other
      therapies. Nerve blocks commonly used for dentistry and oral surgery include the
      infraorbital, maxillary, mental,and mandibular blocks.

PMID- 15979527
TI  - Addressing intimate partner violence in substance-abuse treatment.
AB  - As the use of partner-involved therapies for alcoholism and drug abuse become
      more common in substance-abuse treatment programs, providers are more frequently
      encountering one of the most challenging and politically charged public health
      issues of our time: intimate partner violence (IPV). Recent investigations reveal
      40-60% of married or cohabiting substance-abusing patients report episodes of
      partner aggression in the year preceding entry into treatment. In this article,
      the interrelationship between substance use and IPV is examined, with an emphasis
      on clinical implications and options for substance-abuse treatment providers who
      are often called upon to address IPV during the course of working with their
      patients. We also describe different intervention options for IPV, offer
      recommendations for substance-abuse treatment providers who work with partner
      violent couples, and outline future research directions.

PMID- 15979528
TI  - Involving significant others in the care of opioid-dependent patients receiving
      methadone.
AB  - Positive, abstinence-oriented, social support is associated with good substance
      abuse treatment outcome but few interventions are designed to help patients
      improve their social supports. This article reports on a behavioral intervention
      designed to encourage opioid-dependent patients receiving methadone to include
      drug-free family members or friends in treatment and to use these individuals to
      facilitate development of a supportive, non-drug-using social network. This
      report uses data from a quality assurance program review of the treatment
      response of 59 opioid-dependent outpatients who identified a drug-free
      significant other to participate in their treatment. Fifty-five (93.2%) brought a
      significant other (most often the patient's mother, 29%) to both the initial
      evaluation session and at least one joint session. Social support activities were
      family- (33%), church- (28%), and self-help group-related (30%). Approximately
      78% of patients who participated in the social support intervention achieved at
      least four consecutive weeks of abstinence. Women responded better than men. We
      conclude that methadone-maintained patients can and will include non-drug-using
      family members and friends in treatment, and these individuals can be mobilized
      to help patients improve their recovery.

PMID- 15979529
TI  - Alcohol dependence and posttraumatic stress disorder: differences in clinical
      presentation and response to cognitive-behavioral therapy by order of onset.
AB  - Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) frequently co
      occur. However, little systematic study has examined the importance of their
      temporal order of onset. In this study, differences in clinical presentation and
      response to cognitive-behavioral substance-use therapy by order of onset were
      examined among 94 (51 men and 43 women) individuals with AD and PTSD. The
      findings revealed that women with primary AD and men with primary PTSD presented
      as more distressed and/or depressed than their counterparts at treatment entry. A
      relationship between increased alcohol intake and higher PTSD symptom levels was
      observed during treatment. In general, the primary PTSD group derived greater
      overall benefit (e.g., in physical health, alcohol use, social functioning) as
      compared with the primary AD group. Finally, women with primary AD appeared
      particularly vulnerable to continued psychiatric distress and depression at the
      end of treatment. These findings increase awareness of the importance of
      considering the order of onset and may ultimately lead to treatment improvements
      for this population.

PMID- 15979530
TI  - Adolescents in private chemical dependency programs: who are most at risk for
      HIV?
AB  - Consecutive intakes (N = 419) between ages 13 and 18 years to chemical dependency
      (CD) programs in a large private health plan were interviewed. The prevalence of
      six HIV risk behaviors was measured and categorized into zero, one, and multiple
      risk groups. The relationships between both demographic characteristics and
      substance use with HIV risk behaviors were examined. Approximately half the
      sample reported at least one risk behavior, with 17% reporting multiple risk
      behaviors. Those most likely to report multiple risk behaviors were heavy
      drinking boys, as well as girls who reported using narcotic analgesics.
      Implications of these findings for pediatricians and CD clinicians are discussed.

PMID- 15979531
TI  - Knowledge of hepatitis among active drug injectors at a syringe exchange program.
AB  - Injecting drug users (IDUs) are at high risk for contracting and spreading viral
      hepatitis through nonsterile injection practices, unprotected sexual contact, and
      unsanitary living conditions. We sought to characterize hepatitis knowledge,
      prior testing, and vaccination history among IDUs at a New York City syringe
      exchange program (SEP). IDU subjects generally had a poor understanding of viral
      hepatitis transmission and prevention. We also found low vaccination rates: only
      8% reported receiving hepatitis A vaccine and 11%, hepatitis B vaccine. Educating
      IDUs about risky behaviors and medical preventive interventions, such as vaccines
      for hepatitis A and B and treatment for hepatitis C, may help prevent disease and
      reduce transmission. Stronger linkages between health-care centers and SEPs, drug
      treatment programs, and other service delivery centers where IDUs are encountered
      may promote hepatitis education and vaccination.

PMID- 15979532
TI  - Addiction counseling self-efficacy scale (ACSES): development and initial
      validation.
AB  - This article reports on the development of the Addiction Counseling Self-Efficacy
      Scale (ACSES) through two studies. Exploratory factor analysis yielded a five
      factor solution that accounted for 65% of the variance. The five factors obtained
      assess various aspects of addiction counselors' perceived self-efficacy for
      working with clients in the areas of (a) specific addiction counseling skills,
      (b) assessment, treatment planning, and referral skills, (c) co-occurring
      disorders skills, (c) group counseling skills, and (d) basic counseling skills.
      Reliability estimates suggest that the ACSES is internally reliable. Initial
      criterion validity is supported through comparisons of certified/licensed and
      noncertified/licensed addiction counselors on ACSES scores and among level of
      expertise in the addiction field, specific work activities, and ACSES scores.
      Preliminary evidence indicates that the ACSES is a reliable and valid instrument
      to use when assessing addiction counselors' self-efficacy for working with
      clients. The next steps in the development of ACSES are also discussed.

PMID- 15979533
TI  - Involvement of Alcoholics Anonymous and other self-help groups in professional
      treatment of substance abusers: an Indian perspective.

PMID- 15979534
TI  - The pharmacokinetics of pulmonary insulin in the in vitro isolated perfused rat
      lung: implications of metabolism and regional deposition.
AB  - The pharmacokinetics of several lung disposition pathways for pulmonary insulin
      were studied and modeled in the isolated perfused rat lung (IPRL). Insulin
      solution was administered by forced instillation into the airways of the IPRL as
      0.1 or 0.02 ml doses of coarse spray, with or without bacitracin (BAC), N
      ethylmaleimide (NEM) and atrial natriuretic peptide (ANP). Each insulin
      absorption profile was fitted to a kinetic model that incorporated the
      distribution fraction of the dose reaching the lobar region (DF) and the rate
      constants for absorption into perfusate (k(a)) and non-absorptive loss (k(nal));
      k(nal) was shown to be due to the sum of mucociliary clearance and metabolism.
      Insulin absorption occurred largely by passive diffusion with values for k(a) =
      0.39-0.50 h(-1). With DF = 0.91 following 0.1 ml doses, 11.9 +/- 3.4% of
      bioavailabilities were observed in 1h. In contrast, derived values for k(nal) =
      2.34-3.45 h(-1) were significantly larger than the rate constant for mucociliary
      clearance determined previously in this IPRL (0.96-1.74 h(-1)) due to lung
      metabolism. Indeed, BAC, but neither NEM nor ANP, was found to decrease the value
      of k(nal), which suggested that BAC-inhibitable lung ectopeptidases, and not
      insulin degrading enzyme (IDE), were responsible for this pulmonary metabolism.
      Shallower lung distribution with DF = 0.73 following 0.02 ml doses resulted in
      reduced values for k(a) = 0.27 h(-1) and k(nal) = 2.79 h(-1), indicating that
      these kinetic processes may be lung-region dependent, even within this model and
      emphasizing the likely importance of reliable lung deposition in vivo.

PMID- 15979535
TI  - Can protonated beta-blockers interact with biomembranes stronger than neutral
      isolipophilic compounds? A chromatographic study on three different phospholipid
      stationary phases (IAM-HPLC).
AB  - The chromatographic capacity factors (k') of 10 beta-adrenoceptor antagonists
      ("beta-blockers") were measured on three different immobilized artificial
      membrane-phosphatidylcholine (IAM-PC) HPLC stationary phases, namely IAM-PC-MG,
      IAM-PC-DD2, and IAM-PC-DD. The two former phases are made of phosphatidylcholine
      as found in biomembranes and differ each other in end-capping of free propylamino
      residues whereas the latter is made of single-chain phosphatidylcholine
      analogues. On IAM-PC-DD2 we found that structurally unrelated neutral compounds
      give a single correlation between logk' values and the respective octanol/water
      partition coefficients (logP), as previously observed on IAM-PC-MG phase. This
      was not observed on the IAM-PC-DD phase. IAM chromatography was performed at a pH
      of the aqueous eluent (7.0) close to the physiological pH 7.4. Retention on all
      IAM phases showed a biphasic pattern, being proportional to logP(N)
      (lipophilicity of neutral forms) for more lipophilic congeners (logP(N)>1.90),
      and quite constant for the others. The comparison of beta-blocker retention with
      that of neutral compounds on IAM-PC-MG and IAM-PC-DD2 suggests that they can
      interact with phospholipids as strongly or more strongly than neutral
      isolipophilic compounds, despite their being more than 98% in their ionized form.
      Therefore, we hypothesize that electrostatic interactions play a pivotal role in
      the interactions between beta-blockers and membrane phospholipids.

PMID- 15979536
TI  - A modification of the Hammett equation for predicting ionisation constants of p
      vinyl phenols.
AB  - Currently there are several compounds used as drugs or studied as new chemical
      entities, which have an electron withdrawing group connected to a vinylic double
      bond in a phenolic or catecholic core structure. These compounds share a common
      feature--current computational methods utilizing the Hammett type equation for
      the prediction of ionisation constants fail to give accurate prediction of
      pK(a)'s for compounds containing the vinylic moiety. The hypothesis was that the
      effect of electron-withdrawing substituents on the pK(a) of p-vinyl phenols is
      due to the delocalized electronic structure of these compounds. Thus, this effect
      should be additive for multiple substituents attached to the vinylic double bond
      and quantifiable by LFER-based methods. The aim of this study was to produce an
      improved equation with a reduced tendency to underestimate the effect of the
      double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19
      para-substituted vinyl phenols was used. The ionisation constants were measured
      potentiometrically, and a training set of 10 compounds was selected to build a
      regression model (r2 = 0.987 and S.E. = 0.09). The average error with an external
      test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0.
      Thus, we have been able to significantly improve the existing model for
      prediction of the ionisation constants of substituted p-vinyl phenols.

PMID- 15979538
TI  - Gestational-dependent changes in the expression of signal transduction and
      contractile filament-associated proteins in mouse myometrium.
AB  - OBJECTIVES: The timely onset of powerful uterine contractions during parturition
      involves the integration of many signaling pathways, the protein components of
      which may be translationaly regulated throughout gestation. We have utilized the
      pregnant mouse model to examine gestational-dependent changes in the expression
      of several proteins implicated in the coordination of myometrial excitation
      contraction coupling: caveolins 1-3, rho-associated kinases (ROKalpha and beta),
      alpha-actin, MLC(20), and h-caldesmon. METHODS: Protein expression was examined
      by Western blotting of myometrial homogenates from nonpregnant mice (NP) and
      compared to that from pregnant mice on gestational days 12, 15, 17, and 19 (term
      = day 19). RESULTS: All protein expressions were unchanged during the estrous
      cycle. alpha-Actin was found to be invariant throughout pregnancy. The
      expressions of caveolin-1, -2 and -3, when compared to alpha-actin expression,
      also did not change significantly with mid- to late pregnancy. h-caldesmon: alpha
      actin, ROKalpha:alpha-actin, and ROKbeta:alpha-actin ratios were, however,
      significantly elevated on day 19, whereas MLC(20):alpha-actin was significantly
      down-regulated on day 12 to day 19. Consistent with elevated ROK expression at
      term, the ROK inhibitor Y27632 gave a greater reduction of thromboxane-stimulated
      contractions in myometrium from day 19 mice compared to NP mice. CONCLUSIONS:
      These data suggest that in mouse myometrium there is a dynamic regulation of the
      expression of several proteins implicated in contractile signal integration. This
      may be important for regulating (1) relative uterine quiescence to ensure
      pregnancy progression and (2) priming the tissue for requisite contractile effort
      at term.

PMID- 15979539
TI  - Antidepressant drug use in pregnancy.

PMID- 15979540
TI  - Placental and fetal membrane Nephrin and Neph1 gene expression: response to
      inflammation.
AB  - OBJECTIVE: Fetal and amniotic fluid (AF) proteins (eg, alpha fetoprotein [AFP])
      are measurable in the maternal circulation. Elevated maternal serum AFP levels
      indicate a risk for fetal anomalies or for obstetrical complications that are
      often associated with inflammation (eg, preterm labor). However, little is known
      of the mechanism of protein exchange between the fetus, AF, and maternal
      circulation. Nephrin and Neph1 are cell membrane proteins that restrict
      glomerular protein filtration and which are differentially expressed with renal
      inflammation. We sought to investigate whether nephrin and Neph1 were expressed
      in placenta and fetal membranes, and whether inflammation modified the
      expression. METHODS: Pregnant rats at 18 days' gestation were injected with
      lipopolysacchride (LPS) or control saline intraperitoneally (IP) and killed at 1,
      6, and 12 hours after injection. Placenta and fetal membranes were obtained and
      real-time polymerase chain reaction (PCR) performed for determination of nephrin
      and Neph1 levels. RESULTS: Nephrin and Neph1 were expressed in both placenta and
      fetal membranes. Following maternal LPS administration, nephrin mRNA
      significantly increased in the membranes (0.22 +/- 0.02 to 0.51 +/- 0.050, P
      <.05), while Neph1 expression significantly declined in the placenta (0.19 +/-
      0.05 to 0.10 +/- 0.01, P <.05). CONCLUSION: Fetal membranes and placenta of the
      rat express mRNA for the protein barriers nephrin and Neph 1, suggesting a role
      in the regulation of protein transfer from the fetus to mother. Under basal
      conditions, AF AFP transfer across fetal membranes may account for maternal serum
      AFP levels, whereas gestational inflammatory conditions (eg, preterm labor,
      threatened abortion) may augment AFP transfer across the placenta.

PMID- 15979541
TI  - Effect of pro-inflammatory cytokines on expression and activity of 11beta
      hydroxysteroid dehydrogenase type 2 in cultured human term placental trophoblast
      and human choriocarcinoma JEG-3 cells.
AB  - OBJECTIVE: 11Beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is thought to
      act as a placental barrier protecting the fetus from high levels of maternal
      cortisol. On the other hand, intrauterine infection is one of the main causes of
      preterm birth and adverse fetal outcome, and pro-inflammatory cytokines may
      contribute to these adverse effects. However, the effect of pro-inflammatory
      cytokines on 11beta-HSD2 is still not clear. Therefore, we have evaluated the
      effect of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) on 11beta-HSD2 in cultured human placental trophoblast and in human
      choriocarcinoma JEG-3 cells. METHODS: Placental trophoblast cells were isolated
      from human term placenta. Placental trophoblast cells and JEG-3 cells were
      treated with TNF-alpha (0.1-10 ng/mL) or IL-1beta (0.1-10 ng/mL). Real-time
      reverse transcription polymerase chain reaction and Western blot were used to
      study the regulation of 11beta-HSD2 expression. 11beta-HSD2 activity was
      determined by measuring the rate of cortisol to cortisone conversion in the
      culture medium using thin-layer chromatography (TLC). RESULTS: In placental
      trophoblast, TNF-alpha and IL-1beta down-regulated 11beta-HSD2 mRNA expression
      and activity (both P <.05). The protein level was decreased only with IL-1beta (P
      <.05). In JEG-3 cells, 11beta-HSD2 mRNA was decreased by TNF-alpha but up
      regulated by IL-1beta, with no significant change in protein expression and
      activity. CONCLUSION: Our results suggest caution in interpreting data using JEG
      3 cells. However, our studies with primary trophoblast suggest that TNF-alpha and
      IL-1beta may increase the amount of cortisol crossing to the placenta and fetal
      circulation by attenuating 11beta-HSD2 activity, potentially contributing to
      preterm labor and altered fetal outcome in uterine infection.

PMID- 15979542
TI  - Hypoxia up-regulated angiogenin and down-regulated vascular cell adhesion
      molecule-1 expression and secretion in human placental trophoblasts.
AB  - OBJECTIVE: Many processes that are involved in cellular invasion, including
      blastocyst implantation, placental development, and rapidly growing tumors, occur
      in reduced oxygen environments. It has been surmised that oxygen tension could
      regulate the cytotrophoblast ability to differentiate and, as a consequence, to
      express proteins that are critical for placentation. The objective of the current
      investigation was therefore to test the hypothesis that placental tissues and
      trophoblast cells in culture, under low oxygen tension, release angiogenic
      factors that could affect vascular behavior and invasive potential, thus
      providing a link between abnormal placentation and maternal vascular abnormality.
      METHODS: Functionally active term placental explant culture and trophoblast
      cultures were used to demonstrate the secretion profiles of angiogenin and
      vascular cell adhesion molecule-1 (VCAM-1), and the real-time quantitative
      reverse transcriptase polymerase chain reaction (RT-PCR) technique was employed
      to demonstrate the mRNA expression under both normoxic and hypoxic conditions.
      RESULTS: A significant increase in the secretion (P <.01) and mRNA expression (P
      <.01) of angiogenin and a significant decrease in the secretion (P <.04) and mRNA
      expression (P <.03) of VCAM-1 from both term placental explants and trophoblast
      cultures subjected to hypoxia in vitro were observed. CONCLUSION: Because the
      primary defect in uteroplacental insufficiency is placental maldevelopment
      probably associated with hypoxia in situ, this study provides molecular evidence
      to indicate that the differential expression and secretion of angiogenic factors
      may play an important role in these pathologic conditions.

PMID- 15979543
TI  - Human placental peroxisome proliferator-activated receptor delta and gamma
      expression in healthy pregnancy and in preeclampsia and intrauterine growth
      restriction.
AB  - OBJECTIVES: Human and animal studies have demonstrated that peroxisome
      proliferator-activated receptors (PPARs) are important in placental development
      and play key roles in metabolism and inflammation. We studied placental
      PPARdelta, PPARgamma, and retinoid X receptor alpha (RXRalpha) expression in
      healthy pregnancy and in preeclampsia (PET) and intrauterine growth restriction
      (IUGR). METHODS AND RESULTS: Using immunocytochemistry, PPARdelta, PPARgamma, and
      RXRalpha were localized to the cyto- and syncytiotrophoblast and invading
      trophoblast columns in first and second trimester placentas. Third trimester
      placentas from healthy pregnancy, and in PET and IUGR, demonstrated PPARdelta,
      PPARgamma, and RXRalpha staining within the syncytium, and localization within
      isolated cells in the stroma. In uncomplicated pregnancies, PPARdelta mRNA
      expression (PPARdelta:18s ratio, third trimester median 0.43 [interquartile (IQ)
      range 0.26-0.52] vs first trimester 0.20 [0.00-0.26], P = .03) and PPARdelta
      protein expression (third trimester 3.94 [2.45-4.68] vs first trimester 1.29
      [0.78-2.29] optical densitometry [OD] mm(2), P = .04) were higher in the third
      trimester than in the first trimester. There were no consistent differences in
      PPARdelta, PPARgamma, or RXRalpha mRNA and protein expression among PET or IUGR
      placentas and controls. CONCLUSION: PPARdelta expression is up-regulated between
      the first and third trimester, indicating a role for this nuclear receptor in
      placental function. We found no evidence that placental PPARdelta, PPARgamma, and
      RXRalpha expression is changed in PET or IUGR. This suggests that changes in
      total placental PPAR expression are not involved in the pathophysiology of these
      conditions.

PMID- 15979544
TI  - Adipokine profile and C-reactive protein in pregnancy: effects of glucose
      challenge response versus body mass index.
AB  - OBJECTIVE: To test the hypothesis that gravidas who have an abnormal response to
      glucose loading have dysfunctional adipose tissue cells that produce more insulin
      resistance-inducing and proinflammatory adipokines but less insulin-sensitizing
      adipokines. METHODS: We performed a nested case-control study within a larger
      sample of gravidas who had a glucose challenge test (GCT) at 24-29 weeks; we
      compared 73 cases with an abnormal GCT (>8.3 mM) and 146 controls with a strictly
      normal GCT (<7.2 mM) matched for body mass index (BMI) and height (mean
      difference between cases and controls: 0.1 kg/m(2) and 1 cm, respectively). We
      measured plasma insulin, adipokines (leptin, adiponectin, resistin, tumor
      necrosis factor [TNF]-alpha, interleukin [IL]-6), soluble leptin receptor (sOb
      R), the main leptin-binding protein, and C-reactive protein (CRP). RESULTS: The
      cases showed a 48% increase in insulin concentrations and a 27% increase in TNF
      alpha concentrations compared to the controls (both P < .0001), but leptin, sOb
      R, IL-6, and adiponectin, as well as CRP, concentrations were comparable between
      cases and controls. In the whole group (n = 219), BMI was correlated with
      insulin, leptin, IL-6, and CRP, and inversely with sOb-R and adiponectin
      concentrations (all P < .0003). CONCLUSIONS: Plasma leptin, sOb-R, IL-6, and
      adiponectin, as well as CRP, are strongly related to BMI in gravidas at 24-29
      weeks gestational age but not to the glucose loading response. However, TNF-alpha
      is higher in women with an abnormal GCT. Further studies should disclose the
      source of increased TNF-alpha in these women, and to assess whether TNF-alpha is
      causally related to glucose intolerance during pregnancy.

PMID- 15979545
TI  - The predominant Th1 cytokine profile in maternal plasma of preeclamptic women is
      not reflected in the choriodecidual and fetal compartments.
AB  - OBJECTIVE: Human pregnancy disorders such as preeclampsia are thought to involve
      variations in cytokine levels. It has been proposed that, in preeclamptic women,
      a balance favoring the Th1-type over the Th2-type cytokine profile determines
      local or systemic immunologic responses to pregnancy and that this may cause
      defective placental implantation and placental ischemia, which activate systemic
      endothelial cells. The purpose of this study was to determine whether cytokine
      expression differs in the maternal, choriodecidual, and fetal compartments, and
      between women with or without preeclampsia. METHODS: Plasma concentrations of
      interferon gamma (IFNgamma), interleukin (IL)-2, IL-4, and IL-10 were measured by
      enzyme-linked immunosorbent assay (ELISA) in samples obtained from maternal
      peripheral blood (MPB), choriodecidual (CD), and fetal cord (FC) blood
      compartments of 17 women with preeclampsia and in 15 normotensive women.
      Intracellular concentrations of IFNgamma and IL-2 in T lymphocytes were assessed
      by flow cytometry. RESULTS: Plasma IFNgamma concentrations in both MPB and CD
      compartments were significantly higher in preeclamptic than in normotensive
      women. Maternal plasma IL-4 concentration was significantly lower in preeclamptic
      than in normotensive women. Intracellular IFNgamma and IL-2 concentrations did
      not differ significantly between preeclamptic and normotensive women.
      CONCLUSIONS: The dominant Th1-type over Th2-type cytokine profile is evident in
      MPB, but not in the CD and FC blood compartments. This might reflect the complex
      cytokine networks in the fetal-placental interface and might involve trophoblasts
      or decidual and endothelial cells, which could account for the increased plasma
      IFNgamma concentration and T-helper cell number.

PMID- 15979546
TI  - Feto-maternal bone remodeling in normal pregnancy and preeclampsia.
AB  - OBJECTIVES: To investigate feto-maternal bone turnover in normal pregnancy and
      preeclampsia and to test the hypothesis whether the reported low bone mass at
      birth in small-for-gestational age infants is associated with decreased bone
      formation or increased bone resorption. METHODS: Thirty-two patients with
      preeclampsia (17 mild and 15 severe) and 20 normotensive women (controls) with
      singleton gestations in the third trimester participated in this study.
      Furthermore, 25 nonpregnant healthy women were chosen as nonpregnant controls.
      Maternal 24-hour urine specimens and venous blood samples were collected. In
      addition, fetal cord blood and the first voided neonatal urine were also
      collected. The freshly separated sera were assayed for osteocalcin (OC) and
      carboxy-terminal propeptide of type 1 collagen (PICP) by radioimmunoassay. Urine
      samples were assayed for N-telopeptide of type 1 collagen (NTx) by enzyme-linked
      immunosorbent assay. RESULTS: Maternal and cord serum OC and PICP levels were
      significantly decreased in severe preeclampsia, whereas maternal and first-voided
      neonatal urinary NTx level were significantly increased compared to the
      corresponding levels of controls. In both mother and fetus, the coupling index of
      markers of bone turnover in normal pregnancy or mild preeclampsia was in favor of
      bone formation, whereas in severe preeclampsia the markers suggested marked bone
      resorption. CONCLUSION: Increased bone resorption and decreased bone formation
      occur in preeclampsia in both mother and fetus, being more pronounced in the
      latter. The increased osteoclastic activity in preeclampsia may be attributed to
      increased RANKL induced by increased interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), and transforming growth factor beta2 (TGF-beta2) production.

PMID- 15979547
TI  - The effect of maternal asthma on placental and cord blood protein profiles.
AB  - OBJECTIVE: We conducted a comparative proteomic analysis of placental and
      umbilical cord blood proteins using surface-enhanced laser desorption ionization
      time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among
      asthma, fetal gender, and protein profiles. METHODS: Placental tissue and
      umbilical vein plasma were collected from 10 healthy and 20 asthmatic women.
      Placental proteins were extracted using phosphate-buffered saline containing
      protease inhibitors. Samples were applied to the surfaces of strong anion
      exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity
      capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using a Ciphergen
      Protein Biology System IIc (Freemont, CA), and differences in individual peak
      intensities between groups were determined. RESULTS: Fourteen placental peaks
      were significantly different between asthmatic and non-asthmatic women (seven
      more highly expressed and seven less highly expressed). Ten umbilical cord blood
      peak differences were identified, with four peaks more highly expressed and six
      peaks less highly expressed in asthmatics. Four placental and three umbilical
      cord blood proteins differed significantly between male and female fetuses. Two
      placental and five umbilical cord blood peaks were specifically increased in a
      subgroup of samples collected from asthmatic women who did not use inhaled
      glucocorticoids and were pregnant with a female fetus, a group previously found
      to have altered placental function. CONCLUSIONS: This study demonstrates the
      abilities of the SELDI technique as a tool for protein profiling in tissue or
      plasma. Further work to positively identify the candidate peptides found in this
      study may provide a greater understanding of the placental mechanisms leading to
      alterations in fetal growth in patients with bronchial asthma.

PMID- 15979548
TI  - Maternal fluoxetine infusion does not alter fetal endocrine and biophysical
      circadian rhythms in pregnant sheep.
AB  - OBJECTIVE: Depression during pregnancy is frequently treated with the selective
      serotonin reuptake inhibitor (SSRI), fluoxetine (FX), commonly known as Prozac
      (Eli Lilly & Co, Indianapolis, IN). FX potentiates serotoninergic
      neurotransmission and serotonin has been implicated in the regulation of
      circadian rhythms. We have therefore investigated the effect of chronic
      administration of FX on maternal and fetal circadian rhythms in sheep. METHODS:
      Following an initial bolus dose of 70 mg FX, an 8-day continuous infusion of FX
      (n = 11, 98.5 microg/kg x d) was performed. Controls (n = 13) were treated with
      sterile water vehicle only. Maternal and fetal plasma melatonin and prolactin
      concentrations were determined every 3 hours for 24 hours and then every 6 hours
      for 24 hours beginning on the fourth day of infusion. RESULTS: FX treatment did
      not alter either the basal or circadian rhythms of either maternal or fetal
      plasma melatonin and prolactin concentrations. Fetal cardiovascular and
      behavioral state parameters were measured continuously. While the incidence of
      low-voltage (LV) electrocortical (ECOG) activity was significantly reduced in
      fetuses in the FX group, there was no effect of FX on the diurnal rhythms in
      fetal arterial pressure, heart rate, breathing movements, or behavioral state.
      CONCLUSION: These results show that maternal FX treatment does not result in
      significant alterations in maternal and fetal hormonal and behavioral circadian
      rhythms.

PMID- 15979549
TI  - The interleukin-6 -174G/C promoter polymorphism is not associated with
      endometriosis in South Indian women.
AB  - OBJECTIVE: To investigate the association of the -174 G/C promoter polymorphism
      of the interleukin-6 (IL-6) gene with endometriosis in South Indian women.
      METHODS: The genotype frequencies of the common IL-6 -174 G/C polymorphism were
      compared in infertility patients with (n = 232) and without (n = 210)
      endometriosis using polymerase chain reaction (PCR) and sequencing analysis.
      RESULTS: The genotype frequencies among the cases and controls were G/G 62.9% and
      71.9%, G/C 34.1% and 25.2%, and C/C 3.0% and 2.9%. The G and C allele frequencies
      were 80% and 84.6%, and 20% and 15.4%, respectively. There were no statistically
      significant differences in the genotype distributions or allele frequencies
      between the cases and controls (P = .12). CONCLUSIONS: The present study
      demonstrates no significant association between the IL-6 -174 G/C promoter
      polymorphism and endometriosis in South Indian women.

PMID- 15979550
TI  - Effects of phorbol dibutyrate on cell proliferation, apoptosis, and tumor
      necrosis factor-alpha expression in human endometrial adenocarcinoma cells.
AB  - OBJECTIVES: Recent evidence suggested that protein kinase C (PKC), a major cell
      cycle regulator in endometrial models, mimics progesterone withdrawal by inducing
      downstream signals. In the current study we examined the hypothesis that the PKC
      activator phorbol 12,13 dibutyrate (PDB) would inhibit cell proliferation and
      induce apoptosis in two endometrial adenocarcinoma cell (EAC) lines, HEC-1B and
      Ishikawa cells. We further examined whether the induction of tumor necrosis
      factor-alpha (TNF-alpha) might mediate these effects. METHODS: EAC lines were
      cultured under standard and serum-free conditions to study the effects of PDB on
      cell kinetics. Cell proliferation was determined by cell count using a
      hemacytometer and by incorporation of (3)H thymidine into 10% trichloracetic acid
      precipitable DNA. Apoptosis was determined by measuring cytoplasmic histone
      associated DNA fragments. Conditioned media concentrations of TNF-alpha were
      measured by a commercially available enzyme-linked immunosorbent assay (ELISA).
      EACs were transfected with a -125-bp TNF-alpha promoter luciferase construct and
      treated with PDB to evaluate transcriptional activation. RESULTS: Activation of
      the PKC system with PDB (10 nM) decreased cell proliferation and mitogenesis in
      EACs. PDB induced apoptosis in both EAC lines. EACs exhibit basal TNF-alpha gene
      expression and protein secretion and these were increased potently by PDB.
      However, neutralization of TNF-alpha by addition of anti-TNF-alpha antibodies did
      not prevent the suppression of mitogenesis, induction of apoptosis, or activation
      of TNF-alpha gene expression by PDB. CONCLUSION: Activation of the PKC system
      leads to inhibition of cell proliferation, induction of apoptosis, and TNF-alpha
      expression in EACs. However, apoptosis in this setting does not appear to require
      TNF-alpha action. EACs provide an informative model to investigate aspects of
      endometrial epithelial remodeling that may occur under physiologic conditions of
      progesterone withdrawal.

PMID- 15979551
TI  - Recurrent biparental hydatidiform mole: additional evidence for a 1.1-Mb locus in
      19q13.4 and candidate gene analysis.
AB  - OBJECTIVES: A maternal autosomal recessive mutation causing recurrent
      biparentally inherited complete hydatidiform moles (BiCHM) in affected women was
      previously mapped to a 12.4-cM interval in 19q13.4, which was recently further
      narrowed to a smaller 1.1-Mb region at the centromeric end. It is believed that
      the mutant gene in this condition is a major contributor to the regulation of
      imprinting in the maternal germline. To confirm and possibly narrow the critical
      interval we studied additional rare familial and recurrent cases. METHODS: Using
      polymorphic marker analysis, we first confirmed biparental inheritance on the
      studied molar tissues. We then performed targeted homozygosity mapping with
      markers in 19q13.4 on DNA from affected women of a new large consanguineous
      pedigree, an additional potentially familial case, and three cases with sporadic
      recurrent CHM. Direct sequencing of coding exons and Southern analysis with a
      coding-region probe for one candidate gene (NALP5) was also performed. RESULTS:
      Biparental inheritance was confirmed for those molar tissues available for
      analysis. All women, except for one of the isolated cases, were homozygous for
      markers in the identified 1.1-Mb region in 19q13.4. No mutations or large genomic
      rearrangements were found in NALP5 (MATER), a gene with oocyte-specific
      expression. Heterozygosity for a single-nucleotide polymorphism in exon 13 of
      NALP5 in one patient may refine the candidate region to 1.0 Mb. CONCLUSIONS: The
      reported candidate region for BiCHM in 19q13.4 was confirmed in additional
      families, further establishing it as the major locus that harbors a gene mutated
      in this condition.

PMID- 15979552
TI  - An analysis of fishing vessel accidents.
AB  - In this paper, accident data collected from the Marine Accident Investigation
      Branch are presented and an analysis is carried out to determine the most common
      causes of accidents on fishing vessels. Discussions on fishing vessel-safety
      assessment and data problems are given.

PMID- 15979553
TI  - Time-resolved Forster resonance energy transfer assays for the binding of
      nucleotide and protein substrates to p38alpha protein kinase.
AB  - We have developed assays for the binding of nucleotide and protein substrates to
      p38alpha protein kinase based on time-resolved Forster resonance energy transfer.
      p38alpha was biotinylated by addition of a sequence that targets biotin to a
      single lysine when coexpressed with biotin ligase in Escherichia coli, allowing
      formation of a complex between a streptavidin "LANCE" europium chelate conjugate
      and p38alpha. When this reagent was combined with M39AF, a p38 inhibitor
      containing a fluorescent moiety whose excitation wavelengths match the emission
      wavelengths of the europium chelate, a change in ratio of light emitted at 665
      nm/615 nm is detected. Less than 100pM complex was detected with a
      signal/background ratio of >30-fold. The complex exhibits slow, tight binding
      kinetics where the apparent K(d) decreases with a relaxation time of 21 min at
      125 pM biotin-p38alpha. Preincubating inhibitors or ATP with biotin-p38alpha and
      adding M39AF as a competitor yielded IC(50)s consistent with those measured by
      enzyme assay for the activated form of biotin-p38alpha. The same technique was
      also used to measure affinity of inhibitors for the unphosphorylated and
      catalytically inactive form of biotin-p38alpha. To measure affinity of p38alpha
      for its protein substrate MK2, we incubated biotin-p38alpha with a glutathione S
      transferase MK2 fusion protein. Detection of the complex after incubation with
      streptavidin-allophycocyanin and a LANCE-conjugated anti-GST allowed measurement
      of affinity of MK2 for biotin-p38alpha and detection of 0.5 nM p38alpha.MK2
      complex with signal/background ratio >5-fold. Competition with unbiotinylated
      p38alpha yielded an IC(50) value of 5 nM. Activation of either p38alpha or MK2
      had no effect on the measured K(d). M39AF was found to bind in a ternary complex
      with p38alpha.MK2 with lower affinity than that observed in the binary complex
      with p38alpha alone.

PMID- 15979554
TI  - An agarose-acrylamide composite native gel system suitable for separating ultra
      large protein complexes.
AB  - An agarose-acrylamide composite native gel (CNG) system has been developed for
      separating protein complexes of ultra-large molecular sizes (over 500kDa) and for
      analyzing protein-protein interactions in their native states. Various native gel
      conditions were explored and techniques were improved to facilitate the formation
      and performance of the CNG system. We demonstrate here that the CNG technique is
      capable of resolving a complex of RNA polymerase II and an associated factor from
      the free components, which had not been previously achieved with other methods.
      Furthermore, this CNG electrophoresis can be conveniently coupled to second
      dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis for
      identification of protein components within discrete complexes separated during
      the CNG run. The CNG technique is particularly suitable for capturing dynamic
      protein-protein interactions as exemplified here by the formation and
      demonstration of RNA polymerase II-Fcp1 complex.

PMID- 15979555
TI  - Chloroform phase partitioning for purification of plant-expressed proteins.

PMID- 15979556
TI  - Separation and quantitation of phospholipid hydroperoxide families using high
      performance liquid chromatography with mercury cathode electrochemical detection.
AB  - High-performance liquid chromatography with mercury cathode electrochemical
      detection (HPLC-EC(Hg)) was used to separate and quantify various phospholipid
      hydroperoxide (PLOOH) families. Under the conditions used, baseline separation of
      four major biologically relevant PLOOH classes was achieved. Responsiveness was
      linear up to at least 1 nmol of PLOOH with a detection limit in the subpicomolar
      range (0.1-0.5 pmol). Applying this method to photodynamically stressed murine
      leukemia cells and mitochondria isolated from these cells, we identified and
      quantified PLOOHs derived from phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylserine, and cardiolipin. In terms of high sensitivity, specificity,
      and reliability, HPLC-EC(Hg) has a clear advantage over all other existing
      techniques for determining PLOOHs in complex biological systems.

PMID- 15979557
TI  - Quartz crystal microbalance biosensor study of endothelial cells and their
      extracellular matrix following cell removal: Evidence for transient cellular
      stress and viscoelastic changes during detachment and the elastic behavior of the
      pure matrix.
AB  - A quartz crystal microbalance (QCM) cell biosensor utilizing living endothelial
      cells (ECs) or human breast cancer cells (MCF-7) adhering to the gold QCM surface
      was used to study the relative contributions of the cells and their underlying
      extracellular matrix (ECM) to the measured QCM Deltaf and DeltaR shifts. The ECM
      represents a natural biomaterial that is synthesized by the cells to enable their
      attachment to surfaces. We followed the detachment of the ECs or MCF-7 cells from
      their ECM using a nonproteolytic method and were able to apportion the total
      frequency, Deltaf, decrease of the biosensor into contributions from cell
      attachment and from the intact underlying ECM. We also demonstrated that the
      Deltaf shift remaining after EC removal corresponds to ECM as determined by light
      microscopic visualization of the stained protein. During the process of cell
      detachment, we observed a novel transient increase in viscoelastic behavior
      expressed as a transient increase in the motional resistance, DeltaR, parameter.
      Then we showed via a simulation experiment using ECs stained with fluorescent
      rhodamine-labeled phalloidin, an actin stain, that the transient viscoelastic
      increase correlated with cellular stress exhibited by the cells during removal
      with ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'- tetraacetic acid. Prior
      to cells lifting from their ECM, the attached ECs rearrange their actin
      microfilaments first into peripheral stress fibers and second into internal
      aggregates, to maintain cell-cell connectivity, retain their spread morphology,
      and attempt to adhere more tightly to their underlying ECM. The decrease in
      DeltaR following its transient rise corresponds to cells finally losing their
      attachment focal points and lifting from the ECM. We also characterized the
      normalized f shifts, -Delta(Deltaf)(ECM)/attached cell and 
      Delta(Deltaf)(cells)/attached cell, as a function of varying the number of
      adherent cells. Finally, we demonstrate that the underlying native ECM
      biomaterial, from which all cells have been removed, does not exhibit any
      significant level of energy dissipation, in contrast to the cells when they are
      attached to the ECM.

PMID- 15979558
TI  - Polyethylene glycol-mediated enhancement of the hybridization rate on cDNA
      microarrays.

PMID- 15979559
TI  - High expression with Corynebacterium glutamicum for nuclear magnetic resonance
      sample preparation.

PMID- 15979560
TI  - Mangiferin, a natural occurring glucosyl xanthone, increases susceptibility of
      rat liver mitochondria to calcium-induced permeability transition.
AB  - Mitochondrial permeability transition (MPT) is a Ca(2+)-dependent, cyclosporine A
      sensitive, non-selective inner membrane permeabilization induced by a wide range
      of agents or conditions, which has often been associated with necrotic or
      apoptotic cell death. When mitochondria isolated from livers of rats treated with
      the natural occurring glucosyl xanthone mangiferin (40 mg/kg body weight) were
      exposed in vitro to Ca(2+), they underwent CsA, NEM, and ADP-sensitive high
      amplitude swelling and associated membrane potential dissipation, release of pre
      accumulated Ca(2+), oxidation of thiol groups, and depletion of GSH, without
      changes in the NAD(P)H redox state. The same treatment reduced the
      phosphorylation rate of mitochondria and the resting respiration by around 4 and
      11%, respectively, as well as generation of reactive oxygen species (ROS) by
      organelle. The in vitro exposure of untreated mitochondria to mangiferin plus
      Ca(2+) also resulted in oxidation of thiol groups, in the same way that the
      compound inhibited the Ca(2+)-induced peroxidation of mitochondrial membrane
      lipids. The spectrum of mangiferin during its oxidation by the H(2)O(2)/HRP
      system showed a characteristic absorption peak at 380 nm, which decreased
      immediately after reaction was started; two isosbestic points at around 336 and
      412 nm, with a blue shift in the position of the maxima absorption of mangiferin
      were observed, suggesting their conversion into one oxidation product.
      Glutathione abolished this decrease of absorbance, suggesting that the oxidation
      product of mangiferin forms adducts with GSH. We propose that Ca(2+) increases
      levels of mitochondria-generated ROS, which reacts with mangiferin producing
      quinoid derivatives, which in turn react with the most accessible mitochondrial
      thiol groups, thus triggering MPT. It seems probable that the free radical
      scavenging activity of mangiferin shifts its anti-oxidant protection to the thiol
      arylation. An interesting proposition is that accumulation of mangiferin quinoid
      products would take place in cells exposed to an overproduction of ROS, such as
      cancer cells, where the occurrence of MPT-mediated apoptosis may be a cellular
      defence mechanism against excessive ROS formation.

PMID- 15979561
TI  - Comparative kinetic analysis reveals that inducer-specific ion release precedes
      the mitochondrial permeability transition.
AB  - Relationships among the multiple events that precede the mitochondrial membrane
      permeability transition (MPT) are not yet clearly understood. A combination of
      newly developed instrumental and computational approaches to this problem is
      described. The instrumental innovation is a high-resolution digital apparatus for
      the simultaneous, real-time measurement of four mitochondrial parameters as
      indicators of the respiration rate, membrane potential, calcium ion transport,
      and mitochondrial swelling. A computational approach is introduced that tracks
      the fraction of mitochondria that has undergone pore opening. This approach
      allows multiple comparisons on a single time scale. The validity of the
      computational approach for studying complex mitochondrial phenomena was evaluated
      with mitochondria undergoing an MPT induced by Ca(2+), phenylarsine oxide or
      alamethicin. Selective ion leaks were observed that precede the permeability
      transition and that are inducer specific. These results illustrate the occurrence
      of inducer-specific sequential changes associated with the induction of the
      permeability transition. Analysis of the temporal relationship among the multiple
      mitochondrial parameters of isolated mitochondria should provide insights into
      the mechanisms underlying these responses.

PMID- 15979562
TI  - Observation of the main phase transition of dinervonoylphosphocholine giant
      liposomes by fluorescence microscopy.
AB  - The phase heterogeneity of giant unilamellar dinervonoylphosphocholine (DNPC)
      vesicles in the course of the main phase transition was investigated by confocal
      fluorescence microscopy observing the fluorescence from the membrane incorporated
      lipid analog, 1-palmitoyl-2-(N-4-nitrobenz-2-oxa-1,3-diazol)aminocaproyl-sn
      glycero-3-phosphocholine (NBDPC). These data were supplemented by differential
      scanning calorimetry (DSC) of DNPC large unilamellar vesicles (LUV, diameter
      approximately 0.1 and 0.2 microm) and multilamellar vesicles (MLV). The present
      data collected upon cooling reveal a lack of micron-scale gel and fluid phase
      coexistence in DNPC GUVs above the temperature of 20.5 degrees C, this
      temperature corresponding closely to the heat capacity maxima (T(em)) of DNPC
      MLVs and LUVs (T(em) approximately 21 degrees C), measured upon DSC cooling
      scans. This is in keeping with the model for phospholipid main transition
      inferred from our previous fluorescence spectroscopy data for DMPC, DPPC, and
      DNPC LUVs. More specifically, the current experiments provide further support for
      the phospholipid main transition involving a first-order process, with the
      characteristic two-phase coexistence converting into an intermediate phase in the
      proximity of T(em). This at least macroscopically homogenous intermediate phase
      would then transform into the liquid crystalline state by a second-order process,
      with further increase in acyl chain trans-->gauche isomerization.

PMID- 15979563
TI  - The influence of a visuospatial grounding task on intrusive images of a traumatic
      film.
AB  - Nonclinical participants watched a trauma film under two processing conditions.
      During part of the film participants carried out a concurrent visuospatial
      grounding task consisting of the construction of shapes out of plasticine
      (modelling clay), while the rest of the film constituted a control, no task
      condition. The visuospatial task was predicted to selectively compete for
      processing resources required for intrusive image formation. As predicted,
      spontaneous intrusive images during the succeeding week were significantly less
      common from those parts of the film that coincided with the concurrent task. The
      task had no effect on levels of distress or peritraumatic dissociation,
      consistent with the hypothesis that intrusions were reduced because the task
      competed for resources necessary for encoding into an image-based memory system.

PMID- 15979564
TI  - Identification of a novel calpain inhibitor using phage display.
AB  - Calpains are calcium- and thiol-dependent proteases that cleave a variety of
      intracellular substrates. Overactivation of the calpains has been implicated in a
      number of diseases and conditions such as ischemic stroke indicating a need for
      the development of calpain inhibitors. A major problem with current calpain
      inhibitors has been specific targeting to calpain. To identify highly specific
      calpain interacting peptides, we developed a peptide-phage library screening
      method based on the calcium-dependent conformation change associated with calpain
      activation. A phage-peptide library representing greater than 2 billion expressed
      12-mers was incubated with calpain I in the presence of calcium. The calcium
      dependent bound phage was then eluted by addition of EGTA. After four rounds of
      selection we found a conserved 5-mer sequence represented by LSEAL. Synthetic
      LSEAL inhibited tau-calpain interaction and in vitro proteolysis of tau- and
      alpha-synuclein by calpains. Deletion of the portion of the tau protein
      containing a homologous sequence to LSEAL resulted in decreased calpain-mediated
      tau degradation. These data suggest that these peptides may represent novel
      calpastatin mimetics.

PMID- 15979565
TI  - Use of green fluorescent fusion protein to track activation of the transcription
      factor osterix during early osteoblast differentiation.
AB  - Osterix (Osx) is a transcription factor required for the differentiation of
      preosteoblasts into fully functioning osteoblasts. However, the pattern of Osx
      activation during preosteoblast differentiation and maturation has not been
      clearly defined. Our aim was to study Osx activation during these processes in
      osteoblasts differentiating from murine and human embryonic stem cells (ESC). To
      do this, we constructed an Osx-GFP fusion protein reporter system to track Osx
      translocation within the cells. The distribution of Osx-GFP at representative
      stages of differentiation was also investigated by screening primary osteoblasts,
      mesenchymal stem cells, synoviocytes, and pre-adipocytes. Our experiments
      revealed that Osx-GFP protein was detectable in the cytoplasm of cultured,
      differentiated ESC 4 days after plating of enzymatically dispersed embryoid
      bodies. Osterix-GFP protein became translocated into the nucleus on day 7
      following transfer of differentiated ESC to osteogenic medium. After 14 days of
      differentiation, cells showing nuclear translocation of Osx-GFP formed
      rudimentary bone nodules that continued to increase in number over the following
      weeks (through day 21). We also found that Osx translocated into the nuclei of
      mesenchymal stem cells (C3H10T1/2) and pre-osteoblasts (MC3T3-E1) and showed
      partial activation in pre-adipocytes (MC3T3-L1). These data suggest that Osx
      activation occurs at a very early point in the differentiation of the mesenchymal
      osteoblastic lineage.

PMID- 15979567
TI  - Evidence that the tertiary structure of 20(S)-ginsenoside Rg(3) with tight
      hydrophobic packing near the chiral center is important for Na(+) channel
      regulation.
AB  - Ginsenosides are the active ingredients of Panax ginseng. Ginsenoside Rg(3)
      exists as two stereoisomers of carbon-20: 20-S-protopanaxatriol-3-[O-beta-d
      glucopyranosyl (1-->2)-beta-glucopyranoside] (20(S)-Rg(3)) and 20-R
      protopanaxatriol-3-[O-beta-d-glucopyranosyl (1-->2)-beta-glucopyranoside] (20(R)
      Rg(3)). Recently, we reported that 20(S)-Rg(3) regulates voltage-dependent Ca(2+)
      channel activity and several types of ligand-gated ion channels, whereas 20(R)
      Rg(3) does not have this activity. In this study, we investigated the structure
      activity relationship of these two stereoisomers by NMR spectroscopy and by
      measurement of the current in Xenopus oocytes expressing the mouse cardiac
      voltage-dependent Na(+) channel (Na(v)1.5). We found that 20(S)-Rg(3) but not
      20(R)-Rg(3) inhibited Na(+) channel current in a dose- and voltage-dependent
      manner. The difference between Rg(3) epimers in voltage-dependent ion channel
      regulation indicates that the structure of 20(S)-Rg(3) may be geometrically
      better aligned than that of 20(R)-Rg(3) for interaction with receptor regions in
      Na(+) channels. The (1)H and (13)C NMR chemical shifts, including all hydroxyl
      protons of 20(S)-Rg(3) and 20(R)-Rg(3), were completely assigned, and their
      tertiary structures were determined. 20(S)-Rg(3) has more tight hydrophobic
      packing near the chiral center than 20(R)-Rg(3). Tertiary structures and
      activities of 20(S)-Rg(3) and 20(R)-Rg(3) indicate that 20(S)-Rg(3) may have
      stronger interactions with the receptor region in ion channels than 20(R)-Rg(3).
      This may result in different stereoselectivity of Rg(3) stereoisomers in the
      regulation of voltage-dependent Na(+) channel activity. This is the first
      structural approach to ginsenoside action on ion channel.

PMID- 15979566
TI  - Connexin43 with a cytoplasmic loop deletion inhibits the function of several
      connexins.
AB  - Connexins (Cx) form gap junction channels mediating direct intercellular
      communication. To study the role of amino acids within the cytoplasmic loop, we
      produced a recombinant adenovirus containing Cx43 with a deletion of amino acids
      130-136 (Cx43del(130-136)). Cx43del(130-136) expressed alone in HeLa cells
      localized within the cytoplasm and did not allow transfer of ions, neurobiotin or
      Lucifer yellow. When co-expressed with wild type Cx43, Cx43del(130-136) blocked
      electrical coupling and transfer of neurobiotin or Lucifer yellow. Cx43del(130
      136) and Cx43 co-localized by immunofluorescence and were co-purified from Triton
      X-100-solubilized cell extracts. Intercellular transfer mediated by Cx37 and Cx45
      (but not Cx26 or Cx40) was inhibited when co-expressed with Cx43del(130-136).
      Cx43del(130-136) co-localized with Cx37, Cx40, or Cx45, but not Cx26. These data
      suggest that Cx43del(130-136) produces connexin-specific inhibition of
      intercellular communication through formation of heteromeric connexons that are
      non-functional and/or retained in the cytoplasm.

PMID- 15979568
TI  - Mechanism of arsenite-mediated decreases in CYP3A23 in rat hepatocytes.
AB  - In primary cultures of rat hepatocytes, exposure to arsenite causes a major
      decrease in dexamethasone (DEX)-mediated induction of CYP3A23 hemoprotein, with a
      minor decrease in CYP3A23 mRNA. Here we show that addition of heme did not
      prevent the arsenite-mediated decreases in CYP3A23 protein, and arsenite did not
      decrease intracellular glutathione levels, indicating that heme and glutathione
      were not limiting for formation of holoCYP3A23. We also investigated whether
      arsenite decreases CYP3A23 protein by increasing CYP3A23 degradation by the
      calpain pathway. The calpain inhibitor, calpeptin, caused greater than a 90%
      inhibition of calpain-mediated proteolysis, but had no effect on DEX-mediated
      induction of CYP3A23 protein following 24h treatments. However, calpeptin
      enhanced the effect of arsenite to decrease induction of CYP3A23 protein. In
      addition, in short-term studies, calpeptin appeared to be a suicidal inhibitor of
      CYP3A-catalyzed enzyme activity. Our findings suggest that CYP3A23 protein is not
      degraded by calpain-mediated proteolysis, even in the presence of arsenite.

PMID- 15979569
TI  - Autodisplay of the protease inhibitor aprotinin in Escherichia coli.
AB  - The Kunitz type protease inhibitor aprotinin, containing three intramolecular
      disulfide bonds, was expressed on the surface of Escherichia coli by Autodisplay.
      For this purpose, the aprotinin gene was fused in-frame to the transporter domain
      encoding DNA region of the AIDA-I autotransporter protein. Culture of cells
      supplied with the artificial gene at reducing conditions resulted in the
      translocation of aprotinin to the cell surface. Correct folding of aprotinin was
      shown by high affinity to its target enzyme HLE. No surface translocation was
      detectable under non-reducing conditions, indicating the degradation of aprotinin
      in the periplasm. By the use of periplasmic-protease defective E. coli strains
      PW147, PW151, and PW152, under non-reducing conditions, significant amounts of
      aprotinin appeared in the periplasm but not at the surface. Our results indicate
      that aprotinin molecules, reaching stable conformation before transport across
      the outer membrane, are degraded in the periplasm due to proteolysis. In case
      folding can be prevented, i.e., by blocking disulfide bond formation in the
      periplasm, aprotinin is translocated and can adopt its active conformation at the
      cell surface.

PMID- 15979570
TI  - Odorant binding initially occurring at the central pocket in bovine odorant
      binding protein.
AB  - Why bovine odorant-binding protein (OBPb), among OBP family, assumes a dimeric
      structure has been unclear. Here we clarified, by measuring the fluorescence of
      intrinsic tryptophan and tyrosine residues of intact OBPb and OBPb whose C
      terminal 10 amino acids were deleted, that odorant enters the central pocket
      formed by the dimerization when OBPb first encounters odorant, and odorant with
      high affinity with OBPb subsequently enters the internal cavity (suggested
      binding site), releasing the pre-bound odorant. The internal cavity-bound odorant
      can be released by the binding of other odorants at another internal cavity or at
      the central pocket, depending on the binding odorants. Due to this mechanism
      enabled by the dimerization, OBPb is more reactive than other monomeric OBPs.

PMID- 15979571
TI  - Methoxychlor-induced inducible nitric oxide synthase and proinflammatory
      cytokines expression in macrophages via NF-kappaB, ERK, and p38 mitogen-activated
      protein kinases.
AB  - Methoxychlor (MXC) is a pesticide that was developed as a replacement for
      dichlorodiphenyltrichloroethane. The influence of MXC on cytokine production or
      the functions of macrophages is unclear. This study examined the effects of MXC
      on the production of nitric oxide (NO) and the proinflammatory cytokines (IL
      1beta, IL-6, and TNF-alpha), and analyzed the molecular mechanism in mouse
      macrophages. The addition of MXC to macrophages induced the production of NO and
      proinflammatory cytokines and expression levels of these genes in a dose
      dependent manner. The NF-kappaB sites were identified in the promoter of the iNOS
      and proinflammatory cytokines genes. The transient expression and electrophoretic
      mobility shift assays revealed that the NF-kappaB transcription factor mediated
      the MXC-induced increase in the iNOS and proinflammatory cytokines expression
      levels. In addition, MXC induced the rapid phosphorylation of the ERK1/2 and p38
      MAPK. This demonstrates that MXC stimulates the production of NO and
      proinflammatory cytokines and can up-regulate the expression levels of these
      genes via NF-kappaB transactivation and ERK1/2 and p38 MAPK phosphorylation.
      Overall, this study provides evidence showing that MXC has inflammatory potential
      that is previously unrecognized immunomodulating activity.

PMID- 15979572
TI  - Interference with activity-dependent transcriptional activation of BDNF gene
      depending upon the expanded polyglutamines in neurons.
AB  - Expanded polyglutamines (polyQ) have been demonstrated to impair the CREB
      dependent transcription in established cell lines. Since activity-dependent
      transcription in neurons, which plays an important role in forming neuronal
      plasticity, is largely controlled by CREB, it is important to study whether polyQ
      interferes with the activity-dependent transcriptional activation of genes in
      neurons. In cultured rat cortical neurons, over-expression of truncated
      dentatorubral-pallidoluysian atrophy proteins containing expanded polyQ, which
      form aggregation bodies in nucleus, reduced the calcium (Ca(2+)) signal-mediated
      transcriptional activation of brain-derived neurotrophic factor, c-fos, and
      pituitary adenylate cyclase-activating polypeptide gene promoters in a dose
      dependent manner. The interference with the transcriptional activation was
      dependent upon the presence of polyQ, the strength of which was increased as the
      length of polyQ stretches was expanded. Thus, polyQ interferes with the activity
      dependent transcription in a polyQ-length-dependent manner, which may correspond
      to the severity of polyglutamine diseases.

PMID- 15979573
TI  - Cloning of the hamster p16 gene 5' upstream region and its aberrant methylation
      patterns in pancreatic cancer.
AB  - The hamster model of pancreatic carcinogenesis is useful for understanding the
      development of human pancreatic cancer. However, there is only a small amount of
      hamster genetic information available for analyzing the gene alterations in
      hamster pancreatic cancers. Here, we determined the nucleotide sequence of the 5'
      upstream region of the hamster p16 gene using a suppression polymerase chain
      reaction method combined with gene-specific primers. Based on this sequence, we
      analyzed the methylation status of the 5' region by bisulfite sequencing in three
      normal pancreatic tissues and five pancreatic duct adenocarcinomas (PDAs). All
      five PDAs were highly methylated in the 5' upstream region and showed reduced
      expressions of the p16 gene, while the three normal samples were demethylated.
      The method described in this study is a highly effective and rapid technique for
      determining the 5' upstream region, and is applicable to epigenetic studies of
      the methylation status of this region.

PMID- 15979574
TI  - Upregulation of MUC6 mucin gene expression by NFkappaB and Sp factors.
AB  - To clarify the mechanism underlying regulation of MUC6 expression, we isolated
      the 5' flanking region of the MUC6 gene (5'-MUC6). We determined the
      transcription start site of the MUC6 gene, and found a TATA box at -35 to -29bp,
      a putative NFkappaB consensus sequence at -173 to -164bp, and putative Sp family
      binding sites at -530 to -521 and -847 to -838bp. The luciferase activity of 5'
      MUC6 gradually decreased with deletion of these sites. NFkappaB inhibitory factor
      IkappaB decreased the luciferase activity, and forced expression of NFkappaB
      induced MUC6 transcription. An inhibitor of Sp family binding, mithramycin A,
      suppressed MUC6 transcripts, and Sp1 and Sp3 overexpression up-regulated them.
      Binding of Sp family members to their putative sites was confirmed by
      electrophoretic mobility shift assays. Our results suggest that MUC6
      transcription is regulated by NFkappaB and Sp family members.

PMID- 15979575
TI  - Cloning an artificial gene encoding angiostatic anginex: From designed peptide to
      functional recombinant protein.
AB  - Anginex, a designed peptide 33-mer, is a potent angiogenesis inhibitor and anti
      tumor agent in vivo. Anginex functions by inhibiting endothelial cell (EC)
      proliferation and migration leading to detachment and apoptosis of activated
      EC's. To better understand tumor endothelium targeting properties of anginex and
      enable its use in gene therapy, we constructed an artificial gene encoding the
      biologically exogenous peptide and produced the protein recombinantly in Pichia
      pastoris. Mass spectrometry shows recombinant anginex to be a dimer and circular
      dichroism shows the recombinant protein folds with beta-strand structure like the
      synthetic peptide. Moreover, like parent anginex, the recombinant protein is
      active at inhibiting EC growth and migration, as well as inhibiting angiogenesis
      in vivo in the chorioallantoic membrane of the chick embryo. This study
      demonstrated that it is possible to produce a functionally active protein version
      of a rationally designed peptide, using an artificial gene and the recombinant
      protein approach.

PMID- 15979576
TI  - Interaction between integrin alpha(5) and fibronectin is required for metastasis
      of B16F10 melanoma cells.
AB  - In this study, we report the role of integrin alpha(5) in promoting melanoma
      metastasis. The alpha(5) expression was remarkably elevated in highly metastatic
      B16F10 melanoma cells compared to lowly metastatic B16F1 cells, whereas no
      significant changes were detected in those of integrin alpha(4), alpha(v), and
      beta(1) subunits. Neutralization of alpha(5) with anti-alpha(5) antibody
      significantly suppressed the potential of B16F10 cells for pulmonary metastasis
      in mice and inhibited cell adhesion or spreading to fibronectin in vitro.
      Furthermore, loss of the interaction between alpha(5) and fibronectin diminished
      cell survival and induced apoptosis in B16F10 cells. Above results provide clear
      evidence that integrin alpha(5) is positively correlated with melanoma metastasis
      and might be an anti-melanoma target.

PMID- 15979577
TI  - Detection of Rotavirus from stool samples using a standardized immuno-PCR
      ("Imperacer") method with end-point and real-time detection.
AB  - Immuno-PCR (IPCR) has been studied to increase the detection sensitivity of
      current enzyme-linked immuno-sorbent assays (ELISA) as a novel approach for the
      early detection of Rotavirus infection, a major source for serious diarrhoea for
      susceptible risk groups. IPCR utilizes specific antibody-DNA conjugates with
      subsequent amplification of the marker-DNA. An antibody-DNA conjugate specific
      for Rotavirus antigen VP6 was synthesized and used in combination with a
      commercially available Rotavirus-ELISA kit. IPCR was carried out using reagents
      and protocols of the standardized Imperacer system. Real-time PCR monitoring of
      the marker-DNA amplification was compared to endpoint quantification of amplified
      haptene-labeled PCR products, using a microtiterplate-based PCR-ELISA. In spiked
      calibration samples, as few as 100 virus particles/ml could be clearly detected
      using the IPCR method and either real-time or end-point quantification compared
      to about 100,000 virus particles/ml in ELISA. Rotavirus positive and negative
      stool samples were correctly identified by IPCR with a clear separation even of a
      10,000-fold dilution of the positive stool samples from the negative control.

PMID- 15979578
TI  - Opiate regulation of IL-1beta and TNF-alpha in cultured human articular
      chondrocytes.
AB  - In order to investigate if beta-endorphins anti-inflammatory effect in cartilage
      damaging states is mediated via tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 beta (IL-1 beta), we examined its influence on these two cytokines
      in vitro. Human articular chondrocytes were obtained from patients undergoing
      total knee arthroplasty and stimulated with beta-endorphin (60-6000 ng/ml).
      Protein levels of TNF-alpha and IL-1 beta were measured by ELISA in supernatants
      from articular chondrocyte cultures. beta-Endorphin significantly increased the
      levels of IL-1 beta for all concentrations used after 15 min incubation, and when
      stimulated with 600 and 6000 ng/ml after 24 h incubation. The opioid-induced
      increase in IL-1 beta was blocked by naltrexone in the group tested. TNF-alpha
      expression was also significantly stimulated by 60 and 600 ng/ml beta-endorphin
      after 15 min, an effect blocked by naltrexone in the group tested. These findings
      indicate that the mechanism of beta-endorphins anti-inflammatory influence in
      cartilage-damaging states is not apparently mediated via these two cytokines
      modulation.

PMID- 15979579
TI  - The canonical Wnt signaling pathway promotes chondrocyte differentiation in a
      Sox9-dependent manner.
AB  - To better understand the role of the canonical Wnt signaling pathway in cartilage
      development, we adenovirally expressed a constitutively active (ca) or a dominant
      negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear
      effector of the pathway, in undifferentiated mesenchymal cells, chondrogenic
      cells, and primary chondrocytes, and examined the expression of markers for
      chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of
      the canonical pathway, promoted both chondrogenic differentiation and
      hypertrophy, whereas dnLEF-1 and the gene silencing of beta-catenin suppressed
      LiCl-promoted effects. To investigate whether these effects were dependent on
      Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient
      ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic
      differentiation and hypertrophy in wild-type, but not in Sox9-deficient, cells.
      The response of Sox9-deficient cells was restored by the adenoviral expression of
      Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte
      differentiation in a Sox9-dependent manner.

PMID- 15979580
TI  - GPI-alkaline phosphatase insertion into phosphatidylcholine monolayers: phase
      behavior and morphology changes.
AB  - GPI-anchored proteins are localized on the outer layer of plasma membranes and
      clustered in microdomains generally called lipid rafts. To study the interactions
      between the lipidic GPI-anchor of the protein and phospholipids, we used
      phosphatidylcholine monolayers at the air-water interface as a biomimetic
      membrane system and GPI-alkaline phosphatase prepared from bovine intestinal
      mucosa (GPI-BIAP) as an GPI-anchored protein model. The monolayer technique
      allowed us to define GPI-BIAP interaction with DPPC and POPC, lipids differing
      only by the presence of one unsaturation in their acyl chains. Meanwhile the
      exclusion pressures were similar for the two phospholipids, the comparison of the
      Langmuir isotherms (i.e., pressure/area diagrams) indicates that GPI-BIAP
      interacted differently with DPPC and POPC monolayers. BAM images, acquired in
      order to visualize the interface organization induced by GPI-BIAP incorporation,
      confirm these differences.

PMID- 15979581
TI  - Sites on phospholipase D2 phosphorylated by PKCalpha.
AB  - The phosphorylation sites in phospholipase D2 (PLD2) induced by activation of
      protein kinase Calpha (PKCalpha) in COS 7 cells were analyzed by mass
      spectrometry. Ser134, 146, and 243, and Thr72, 99/100, and 252 were identified.
      These sites were mutated to Ala and the double mutation of Ser243 and Thr252
      eliminated the phosphorylation. However, the PLD2 activity, and the binding
      between PKCalpha and PLD2 were unaffected by the mutations. We conclude that
      phosphorylation of these residues is not required for PLD2 activation by
      PKCalpha, and that protein-protein interaction between PLD2 and PKCalpha is
      sufficient to activate PLD2.

PMID- 15979582
TI  - Hemoglobin is expressed in alveolar epithelial type II cells.
AB  - Hemoglobin is the main oxygen carrying heme protein in erythrocytes. In an effort
      to study the differential gene expression of alveolar epithelial type I and type
      II cells using DNA microarray technique, we found that the mRNAs of hemoglobin
      alpha- and beta-chains were expressed in type II cells, but not in type I cells.
      The microarray data were confirmed by RT-PCR. The mRNA expression of both chains
      decreased when type II cells trans-differentiated into type I-like cells.
      Immunocyto/histochemistry revealed that hemoglobin protein was specifically
      localized in type II cells of a lung cell mixture and rat lung tissue. The
      endogenous synthesis of hemoglobin in alveolar epithelial cells suggests that
      hemoglobin may have unidentified functions other than oxygen transport in the
      lung.

PMID- 15979583
TI  - Evolutionary conservation of nuclear and nucleolar targeting sequences in yeast
      ribosomal protein S6A.
AB  - Over 1 billion years ago, the animal kingdom diverged from the fungi.
      Nevertheless, a high sequence homology of 62% exists between human ribosomal
      protein S6 and S6A of Saccharomyces cerevisiae. To investigate whether this
      similarity in primary structure is mirrored in corresponding functional protein
      domains, the nuclear and nucleolar targeting signals were delineated in yeast S6A
      and compared to the known human S6 signals. The complete sequence of S6A and cDNA
      fragments was fused to the 5'-end of the LacZ gene, the constructs were
      transiently expressed in COS cells, and the subcellular localization of the
      fusion proteins was detected by indirect immunofluorescence. One bipartite and
      two monopartite nuclear localization signals as well as two nucleolar binding
      domains were identified in yeast S6A, which are located at homologous regions in
      human S6 protein. Remarkably, the number, nature, and position of these targeting
      signals have been conserved, albeit their amino acid sequences have presumably
      undergone a process of co-evolution with their corresponding rRNAs.

PMID- 15979584
TI  - A fast, simple method for screening radiation susceptibility genes by RNA
      interference.
AB  - Radiotherapy can cause unacceptable levels of damage to normal tissues in some
      cancer patients. To understand the molecular mechanisms underlying radiation
      induced physiological responses, and to be able to predict the radiation
      susceptibility of normal tissues in individual patients, it is important to
      identify a comprehensive set of genes responsible for radiation susceptibility.
      We have developed a simple and rapid 96-well screening protocol using cell
      proliferation assays and RNA interference to identify genes associated with
      radiation susceptibility. We evaluated the performance of alamarBlue-, BrdU-, and
      sulforhodamine B-based cell proliferation assays using the 96-well format. Each
      proliferation assay detected the known radiation susceptibility gene, PRKDC. In a
      trial screen using 28 shRNA vectors, another known gene, CDKN1A, and one new
      radiation susceptibility gene, ATP5G3, were identified. Our results indicate that
      this method may be useful for large-scale screens designed to identify novel
      radiation susceptibility genes.

PMID- 15979585
TI  - Evidence against adenosine analogues being agonists at the growth hormone
      secretagogue receptor.
AB  - Adenosine and adenosine analogues have been reported to act as agonists or
      partial agonists at the growth hormone secretagogue receptor 1a (GHSR1a). We have
      re-examined this question. A concentration-dependent increase in intracellular
      calcium concentration ([Ca(2+)](i)) was observed in GHSR1a transfected HEK 293
      EBNA cells stimulated with adenosine (EC50: 0.2 microM) or 2-chloroadenosine
      (EC50: 1.1 microM) but also in untransfected HEK 293-EBNA cells stimulated with 2
      chloroadenosine (EC50: 0.67 microM) or 5'-N-ethylcarboxamidoadenosine (NECA)
      (EC50: 0.045 microM). These findings support endogenous expression of adenosine
      receptors, presumably A(2B) receptors in HEK 293-EBNA cells. In GHSR1a
      transfected CHO cells, lacking adenosine receptors, the GHSR1a agonist hGhrelin
      (EC50: 2.4 nM) increased [Ca(2+)](i), but no effects of adenosine, 2
      chloroadenosine or NECA were detected. An inverse agonist of GHSR1a, [d-Arg-1, d
      Phe-5, d-Trp-7, 9, Leu-11] substance P, reduced hGhrelin effects but adenosine, 2
      chloroadenosine or 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) did not. NECA
      increased the [Ca(2+)](i) in co-transfected (GHSR1a and A(2B) receptor) CHO cells
      (EC50: 0.053 microM), but no additive or synergistic effects on [Ca(2+)](i) or
      cAMP formation were observed after stimulation with NECA in the absence or in the
      presence of hGhrelin. In binding studies on GHSR1a transfected CHO cell
      membranes, [(125)I]-hGhrelin binding could be displaced by the GHSR1a agonist MK
      0677 (IC50: 0.34 nM), hGhrelin (IC50: 1.5 nM), and the substance P analogue
      (IC50: 0.64 microM) but not by adenosine or 2-chloroadenosine. We conclude that
      adenosine and analogues do not act as agonists or partial agonists at the GHSR1a
      and that cross-talk between the GHSR1a and A(2B) receptors is limited.

PMID- 15979586
TI  - Structure activity relationships and quantitative structure activity
      relationships for the flavonoid-mediated inhibition of breast cancer resistance
      protein.
AB  - Breast cancer resistance protein (BCRP) is a newly identified ABC transporter,
      which plays an important role in drug disposition and represents an additional
      mechanism for the development of MDR. Flavonoids, a major class of natural
      compounds widely present in foods and herbal products, have been shown to be BCRP
      inhibitors. The objective of the present study was to elucidate the SAR and
      derive a QSAR model for flavonoid-BCRP interaction. The EC(50) values for
      increasing mitoxantrone accumulation in MCF-7 MX100 cells for 25 flavonoids, from
      five flavonoid subclasses, were determined in this study or obtained from our
      previous publication [Zhang S, Yang X, Morris ME. Combined effects of multiple
      flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm
      Res 2004;21(7):1263-73], and ranged from 0.07+/-0.02 microM to 183+/-21.7 microM.
      We found that the presence of a 2,3-double bond in ring C, ring B attached at
      position 2, hydroxylation at position 5, lack of hydroxylation at position 3 and
      hydrophobic substitution at positions 6, 7, 8 or 4', are important structural
      properties important for potent flavonoid-BCRP interaction. These structural
      requirements are similar but not identical to those for potent flavonoid-NBD2 (P
      glycoprotein) interaction, indicating that inhibition of BCRP by flavonoids may
      involve, in part, the binding of flavonoids with the NBD of BCRP. In addition, a
      QSAR model consisting three structural descriptors was constructed, and both
      internally and externally validated, suggesting the model could be used to
      quantitatively predict BCRP inhibition activity of flavonoids. These findings
      should be useful for predicting BCRP inhibition activity of other untested
      flavonoids and for guiding the synthesis of potent BCRP inhibitors for potential
      clinical application.

PMID- 15979587
TI  - Gonadotropin-inhibiting hormone stimulates feeding behavior in chicks.
AB  - Neuropeptides containing a C-terminal Arg-Phe-NH2 motif (RFamide peptides) are
      suggested to be involved in the control of feeding behavior in both invertebrates
      and vertebrates. Gonadotropin-inhibitory hormone (GnIH) is the first identified
      avian RFamide peptide that inhibits gonadotropin release from the pituitary. The
      GnIH precursor encodes one GnIH and its related peptides (GnIH-RP-1 and -RP-2)
      that shared the same C-terminal motif, Leu-Pro-Xaa-Arg-Phe-NH2 (Xaa = Leu or Gln)
      (LPXRFamide). GnIH neurons are localized in the paraventricular nucleus, with
      their fibers visible in multiple brain locations including the median eminence
      and brainstem. In this study, we therefore investigated the action of GnIH and
      its related peptides on feeding behavior. Intracerebroventricular (ICV) injection
      of GnIH, GnIH-RP-1 and GnIH-RP-2 significantly stimulated food intake in chicks.
      The chicken pentapeptide LPLRFamide, a degraded C-terminus of GnIH and GnIH-RP-1,
      did not stimulate feeding thereby demonstrating the importance of the N-terminus
      of GnIH and its related peptides for the orexigenic effect. Anti-GnIH antiserum
      suppressed appetite induced by fasting, but did not modify feeding under ad
      libitum conditions. The present study suggests that GnIH and its related peptides
      act as endogenous orexigenic factors in the brain of chicks.

PMID- 15979588
TI  - Trigeminal pain transmission requires reactive oxygen species production.
AB  - Three experiments were conducted in order to investigate the possible involvement
      of the reactive oxygen species in the nociception within the subnucleus caudalis
      of the spinal trigeminal nucleus (Vc). In the first experiment the extracellular
      level of hydrogen peroxide was evaluated by microdialysis in the Vc of two groups
      of six rats before and after a formalin (group 1) or saline solution (group 2)
      injection into the upper lip. In the second experiment the formalin test was
      conducted in three groups of 6 rats after a microinjection of 2-methoxyestradiol
      (2-ME, a superoxide-dismutase inhibitor; group 1) or N-acetylcysteine (NAC, an
      oxygen intermediate scavenger; group 2) or saline solution (group 3) into the Vc.
      In the third experiment an histochemical assay for superoxide dismutase activity
      was performed on two groups of 4 rats each 2 h after a formalin (group 1) or
      saline solution (group 2) injection into the upper lip. The results showed that
      (1) the level of hydrogen peroxide increases into the Vc during facial pain (134%
      of baseline); (2) the inhibition of superoxide dismutase or the removal of oxygen
      intermediate within the Vc decreases the sensibility to facial pain stimuli; and
      (3) persistent facial pain stimuli decrease the superoxide activity into the Vc
      (90% of counter-lateral). These data indicate that reactive oxygen species are
      produced in the Vc during persistent facial pain and are necessary for the
      transmission of pain.

PMID- 15979589
TI  - Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity
      in primary cultured retinal ganglion cells.
AB  - Erythropoietin receptor (EpoR) is expressed in the central nervous system (CNS),
      however, no clear consensus has been obtained whether Epo acts as a prosurvival
      factor in neurons. Because retinal ganglion cell (RGC) death is a common cause of
      reduced visual function in several ocular diseases, we explored whether Epo might
      potentially be beneficial in protecting RGCs from glutamate and nitric oxide (NO)
      induced cytotoxicity, using isolated RGCs by a two-step panning method. Brain
      derived neurotrophic factor (BDNF) was used as a positive control. EpoR mRNA was
      expressed in isolated RGCs, and EpoR protein was expressed on the RGCs in the
      normal and ischemic retinas. Epo had less potential to improve the survival of
      primary RGCs in serum-free medium than BDNF. In these cells, BDNF, but not Epo,
      downregulated the expression of Bim, a proapoptotic Bcl-2 family member that
      plays a key role in cytokine-mediated cell survival, suggesting a possible
      mechanism for this difference. When RGCs were cultured with glutamate or an NO
      generating reagent, the survival of RGCs was compromised, and Bcl-2 expression
      was decreased in these cells. Both Epo and BDNF significantly reduced RGC death
      induced by glutamate and NO. In agreement with this, these factors reversed the
      Bcl-2 expression. These findings suggest that Epo may be a potent neuroprotective
      therapeutic agent for the treatment of ocular diseases that are characterized by
      RGC death.

PMID- 15979590
TI  - Cyclooxygenase-2 expression is induced in rat brain after kainate-induced
      seizures and promotes neuronal death in CA3 hippocampus.
AB  - Cyclooxygenase-2 (COX-2) is the predominant isoform of cyclooxygenase in brain.
      COX-2 activity produces oxidative stress and results in the production of
      prostaglandins that have many injurious effects. COX-2 transcription is induced
      by synaptic activity; therefore, COX-2 activity could contribute to epileptic
      neuronal injury. To address this hypothesis, COX-2 protein expression and PGE2
      production were determined after kainate-induced limbic seizures in rats. The
      effects of a specific COX-2 inhibitor, SC58125, on neuronal survival and PGE2
      concentration in the hippocampus were also determined. COX-2 protein expression
      was increased in CA3, dentate gyrus, and cortex at 18-24 h after seizures.
      Hippocampal PGE2 levels were increased at 24 h following seizures, and treatment
      with the selective COX-2 inhibitor SC58125, 3 mg/kg p.o., attenuated the increase
      in PGE2 concentration. The survival of CA3 neurons at 7 days after seizures was
      increased in rats treated with SC58125 compared to vehicle controls. There was no
      effect of drug treatment on body or brain temperature, nor on the duration or
      rate of Type IV EEG activity. These results suggest that COX-2 activity can
      contribute to epileptic neuronal injury and that selective COX-2 inhibitors are
      neuroprotective.

PMID- 15979591
TI  - Prepulse inhibition and fear-potentiated startle are altered in tissue inhibitor
      of metalloproteinase-2 (TIMP-2) knockout mice.
AB  - The ability to discriminate between potential dangers and recall those stimuli is
      essential for survival. This emotional learning requires the involvement of
      higher brain structures, including the amygdala, hippocampus and related cortical
      structures. Long-term changes in synaptic transmission and structure are
      important for the establishment and consolidation of fear memory. The structural
      changes associated with this synaptic plasticity likely require alterations in
      the composition of the extracellular matrix (ECM). ECM integrity is maintained by
      the opposing action of matrix metalloproteinases (MMPs) and their specific
      inhibitors, tissue inhibitors of metalloproteinases (TIMPs). To date, no studies
      have examined the role of MMPs or TIMPs in conditioned fear. Here, we show that
      neither male nor female mice deficient in TIMP-2 (knockout) exhibit prepulse
      inhibition of the startle reflex, suggesting deficits in pre-attentional
      sensorimotor gating. In addition, knockout mice and mice expressing a mutant
      truncated TIMP-2 (knock-down) show deficits in fear-potentiated startle. This is
      the first report of a phenotype for the TIMP-2(-/-) mice and suggests that TIMP-2
      may play a role in the synaptic plasticity underlying learning and memory.

PMID- 15979592
TI  - Hindlimb loading determines stepping quantity and quality following spinal cord
      transection.
AB  - We compared the bipedal hindlimb stepping ability of untrained and trained (step
      trained 6 min/day) spinal rats (mid-thoracic spinal cord transection at post
      natal day 5) at different levels of body weight support on a treadmill over a 40
      day period, starting at 69 days of age. A robotic device provided precise levels
      of body weight support and recorded hindlimb movement. We assessed stepping
      ability using: (1) step quantity determined from the measured hindlimb movement,
      (2) ordinal scales of paw placement, weight-bearing, and limb flexion, and (3)
      the lowest level of body weight support at which stepping was maintained.
      Stepping quantity and quality depended strongly on the level of support provided.
      Stepping ability improved with time, but only at the higher levels of weight
      bearing, and independently of training. Increasing limb loading by gradually
      decreasing body weight support altered the spatiotemporal properties of the
      steps, resulting in an increase in step length and stance duration and a decrease
      in swing and step cycle duration. The rats progressively improved their ability
      to support more load before collapsing from a maximum of about 42 g (
      approximately 25% of body weight) at Day 1 to 73 g ( approximately 35% of body
      weight) at Day 40. We conclude that the level of hindlimb loading provided to a
      spinally transected rat strongly influences the quantity and quality of stepping.
      Furthermore, the relationship between stepping ability and loading conditions
      changes with time after spinal cord transection and is unaltered by small amounts
      of step training. Finally, load-bearing failure point can be a quantitative
      measure of locomotor recovery following spinal cord injury, especially for
      severely impaired animals that cannot step unassisted.

PMID- 15979593
TI  - Proteolysis of neuronal cytoskeletal proteins by calpain contributes to rat
      retinal cell death induced by hypoxia.
AB  - Our previous studies in retina on the mechanism for hypoxia-induced cell death
      suggested activation of a class of calcium-activated proteases known as calpains.
      This conclusion was based on data showing proteolysis of a calpain substrate
      alpha-spectrin, autolysis of activated calpain, and reduction of cell damage by
      calpain inhibitor SJA6017. Less is known about changes in downstream pathways
      after calpain activation. Thus, the purpose of the present investigation was to
      measure proteolysis of neuronal cytoskeletal proteins and apoptotic cell
      signaling factors during hypoxia-induced retinal cell death. Rat retinas were
      incubated in RPMI medium with glucose and 95% O2/5% CO2 to supply sufficient
      oxygen for retinal cell survival. Hypoxia was induced with 95% N2/5% CO2 without
      glucose. Immunoblotting was used to detect activation of calpain and proteolysis
      of substrates. Amounts of mRNA for calpain 1 and 2 were determined by
      quantitative PCR. Twelve times more calpain 2 mRNA than calpain 1 was present in
      retinas. Activation of calpain 2 and production of a calpain-specific alpha
      spectrin breakdown product at 150 kDa were confirmed in hypoxic retinas. Further,
      pro-caspase-3 at 32 kDa was proteolyzed to a fragment at 30 kDa, tau protein was
      lost, and p35 was proteolyzed to p25 suggesting prolonged activation of cdk5.
      SJA6017 partially inhibited the production of these fragments. During hypoxia in
      rat retinas, calpains may be major proteases causing breakdown of neuronal
      proteins involved in apoptotic cell death. Calpain inhibitor SJA6017 may have
      potential for testing as a therapeutic agent against retinal pathologies such
      those caused by glaucoma, although future studies such as testing in in vivo
      animal models are required.

PMID- 15979594
TI  - Enhanced hippocampal acetylcholine release in nociceptin-receptor knockout mice.
AB  - Nociceptin (NOC), an endogenous ligand of the opioid receptor-like 1 receptor, is
      thought to be involved in learning and memory processes. Since acetylcholine
      (ACh) is involved in hippocampal function, and the hippocampus plays a critical
      role on the learning and memory function, hippocampal ACh release in NOC-receptor
      knockout mice was examined using an in vivo microdialysis method. The release of
      hippocampal ACh was largely increased in the knockout mice. Furthermore, in the
      knockout mice, an enhanced hippocampal theta rhythm, which is known to be linked
      to hippocampal memory function, was also observed. Immunohistochemically, in
      septum, co-existence of NOC receptor with cholinergic, but not with GABAergic
      neurons, was verified. The findings demonstrate that the NOC receptor is involved
      in hippocampal cholinergic function.

PMID- 15979595
TI  - Orexin A in the nucleus accumbens stimulates feeding and locomotor activity.
AB  - Due to the nature of processing within the accumbens shell (AccSh) and the
      presence of orexin receptors and varicosities within the AccSh, we hypothesized
      that orexin A may partly regulate feeding behavior and locomotor activity via
      signaling in this site. To test this hypothesis, male Sprague-Dawley rats were
      implanted with guide cannulae directed to the medial portion of the AccSh. Orexin
      A (0, 100, 500, and 1000 pmol, in 0.5 microl artificial cerebrospinal fluid) was
      infused into the AccSh and feeding behavior and locomotor activity were
      monitored. The effect of pretreatment with an orexin 1 receptor antagonist
      (SB334867A) on orexin A-induced feeding and locomotor activity was assessed.
      Orexin A augmented feeding in the 0-1 h and 1-2 h post-infusion interval (P =
      0.0058 and P = 0.025, respectively) and stimulated locomotor activity in the 30
      60 min, 60-90 min, and 90-120 min post-infusion intervals (P <or= 0.0001, P =
      0.0056 and P = 0.046, respectively). Orexin A-induced feeding was significantly
      attenuated by preadministration of SB334867A in the 0-1 h post-infusion time
      interval (P = 0.03). Orexin A-induced locomotor activity was not affected by
      SB334867A. These data support the hypothesis that the AccSh is a site of orexin A
      modulation of feeding behavior and locomotor activity.

PMID- 15979596
TI  - Structure of the O-polysaccharide of Proteus mirabilis OC (CCUG 10702) from a new
      proposed Proteus serogroup O75.
AB  - A neutral O-polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of Proteus mirabilis OC (CCUG 10702) and studied by sugar and
      methylation analyses and (1)H and (13)C NMR spectroscopy. The following structure
      of the tetrasaccharide repeating unit of the polysaccharide was established:
      [structure: see text]. Based on the unique structure of the O-polysaccharide and
      serological data, we propose classifying P. mirabilis OC (CCUG 10702) into a new
      separate Proteus serogroup O75. A weak cross-reaction of O-antiserum against P.
      mirabilis OC with the lipopolysaccharide of P. mirabilis O49 was accounted for by
      a similarity in the O-polysaccharide structures.

PMID- 15979597
TI  - Structure-immunomodulating activity relationships of a pectic arabinogalactan
      from Vernonia kotschyana Sch. Bip. ex Walp.
AB  - Structure and immunological characteristics of the pectic arabinogalactan Vk2a
      (previously reported as Vk100A2a) from the roots of Vernonia kotschyana Sch. Bip.
      ex Walp. were investigated after enzymatic digestion of the galacturonan moiety
      and the side chains of the rhamnogalacturonan structure of Vk2a. endo-alpha-D-(1-
      >4)-Polygalacturonase digestion released the high molecular weight 'hairy region'
      (Vk2a-HR) and oligogalacturonides. Vk2a-HR consisted of GalA (4-linked) and Rha
      (2- or 2,4-linked) in a 1:1 ratio, with 60% of Rha branched at C-4. The Rha
      located in the rhamnogalacturonan core was branched randomly by Gal units. Vk2a
      HR was rich in neutral sugars such as Araf 5- (12.2%) and 3,5-substituted (12.8%)
      and terminally- (14.1%) linked and Gal 4- (13.0%), 3- (0.9%), 6- (2.2%) and 3,6-
      (1.1%) substituted. Arabinans with chain lengths up to 11 units were identified.
      Araf residues were attached to C-3 of alpha-L-(1-->5)-Araf chains and to C-4 of
      Gal residues. Single Gal units and chains of beta-D-(1-->6)-linked galacto di- to
      penta-saccharides were attached to a beta-D-(1-->3)-galactan core. All the enzyme
      resistant fractions expressed potent complement fixation and induction of B-cell
      mitogenic activity, and the present study indicates that there may be several and
      possibly structurally different active sites involved in the bioactivity of Vk2a.
      The bioactive sites may be located both in the more peripheral parts of the
      molecule but also in the inner core of the 'hairy region' or in larger enzyme
      resistant chains.

PMID- 15979598
TI  - N-Alkyl derivatives of 2-amino-2-deoxy-D-glucose.
AB  - Mono- and di-N-alkylated derivatives of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy
      beta-D-glucose (alkyl=methyl, ethyl, propyl, butyl, pentyl, hexyl, benzyl) were
      synthesised by the reductive alkylation of per-O-acetyl-d-glucosamine. (N-ethyl,
      N-propyl, N-butyl, N-pentyl and N-hexyl)-1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy
      beta-D-glucoses were deacetylated in order to attempt an enzymatic
      phosphorylation. All products were characterised by means of IR, NMR and MS
      spectra. N-Ethyl- and N-pentyl-d-glucosamines were found to exhibit weak
      antifungal activity.

PMID- 15979599
TI  - The long QT syndrome: therapeutic implications of a genetic diagnosis.
AB  - The congenital long QT syndrome (LQTS) is a hereditary disorder characterized by
      a prolonged QT interval and a polymorphic ventricular tachycardia, known as
      torsade de pointes (TdP), leading to severe cardiac events such as syncope and/or
      sudden cardiac death. Molecular genetic studies have revealed a total of eight
      forms of congenital LQTS caused by mutations in genes of the potassium, sodium
      and calcium channels or membrane adapter located on chromosomes 3, 4, 7, 11, 12,
      17 and 21. Genotype-phenotype correlation in clinical and experimental studies
      has been investigated in detail in the LQT1, LQT2 and LQT3 syndromes which
      constitute more than 90% of genotyped patients with LQTS, enabling us to stratify
      risk and to effectively treat genotyped patients.

PMID- 15979600
TI  - The hills and valleys of an impact factor.

PMID- 15979601
TI  - Reassessing the increased glycation of hemoglobin in nondiabetic chronic renal
      failure patients: a hypothesis on the role of lipid peroxides.
AB  - BACKGROUND: Glycated hemoglobin (HbA(1C)) is considered clinically useful for
      assessing long-term integrated control of blood glucose in diabetes. However, an
      increased HbA(1C) concentration has been documented in chronic renal failure
      (CRF) patients without any history of diabetes. Collective evidences reveal that
      lipid peroxidation (MDA) can modulate protein glycation. We evaluated the
      relationship between glycated hemoglobin (HbA(1C)) and lipid peroxidation in non
      diabetic CRF patients. METHODS: Twenty-eight nondiabetic CRF and 23 age- and sex
      matched healthy subjects were enrolled for this study. Plasma urea, creatinine,
      lipid peroxides, fasting glucose and HbA(1C) were analyzed in both the groups.
      The in-vitro effect of MDA on glycation of hemoglobin was studied by incubating
      healthy erythrocytes with either 5 or 50 mmol/l glucose concentration. RESULTS:
      The percentage of HbA(1C) concentrations and plasma malondialdehyde (MDA) were
      significantly increased in CRF patients compared to control subjects. When the
      effects of uremia and blood glucose on the concentration of HbA(1C) was refuted
      by partial correlation analysis, MDA was found to be a significant determinant of
      HbA(1C) (r=0.41, p=0.04) in patients with renal failure. In-vitro incubation of
      RBC with glucose along with MDA was found to enhance the process of hemoglobin
      glycation. CONCLUSION: Our results suggest that lipid peroxidation per se can
      contribute to glycation of hemoglobin, warranting extra-precaution in
      interpreting HbA(1C) as a measure of glycemic control in CRF.

PMID- 15979602
TI  - Pathophysiology of fetal microchimeric cells.
AB  - Microchimerism has been defined by the presence of a low number of circulating
      cells transferred from one individual to another. The transfer of microchimeric
      cells naturally takes place during pregnancy and occurs bi-directionally between
      the mother and fetus. Further, microchimerism can also be a result of blood
      transfusions and organ transplants. Microchimeric cells have been implicated in
      health and disease. Fetal microchimerism has been correlated with the
      hyporesponsiveness of the maternal immune system towards a fetal allograft and
      with the longevity of organ transplants. However, microchimeric cells have been
      implicated in the pathogenesis of autoimmune diseases including systemic
      sclerosis. In contrast, microchimeric cells were found to contribute to tissue
      repair. Much controversy exists around the role of microchimeric cells in the
      pathogenesis of certain diseases, and these cells in tissues may be a consequence
      rather than the cause of disease.

PMID- 15979603
TI  - Stochastic model for outcome prediction in acute illness.
AB  - The aims were to apply a stochastic model to predict outcome early in acute
      emergencies and to evaluate the effectiveness of various therapies in a
      consecutively monitored series of severely injured patients with noninvasive
      hemodynamic monitoring. The survival probabilities were calculated beginning
      shortly after admission to the emergency department (ED) and at subsequent
      intervals during their hospitalization. Cardiac function was evaluated by cardiac
      output (CI), heart rate (HR), and mean arterial blood pressure (MAP), pulmonary
      function by pulse oximetry (SapO(2)), and tissue perfusion function by
      transcutaneous oxygen indexed to FiO(2),(PtcO(2)/FiO(2)), and carbon dioxide
      (PtcCO(2)) tension. The survival probability (SP) of survivors averaged 81.5+/
      1.1% (SEM) and for nonsurvivors 57.7+/-2.3% (p<0.001) in the first 24-hour period
      of resuscitation and subsequent management. The CI, SapO(2),PtcO(2)/FiO(2) and
      MAP were significantly higher in survivors than in nonsurvivors during the
      initial resuscitation, while HR and PtcCO(2) tensions were higher in the
      nonsurvivors. Predictions made during the initial resuscitation period in the
      first 24-hours after admission were compared with the actual outcome at hospital
      discharge, which were usually several weeks later; misclassifications were 9.6%
      (16/167). The therapeutic decision support system objectively evaluated the
      responses of alternative therapies based on responses of patients with similar
      clinical-hemodynamic states.

PMID- 15979604
TI  - Novel genes controlling ventral cord asymmetry and navigation of pioneer axons in
      C. elegans.
AB  - The ventral cord in C. elegans is the major longitudinal axon tract containing
      essential components of the motor circuit. In genetic screens using transgenic
      animals expressing neuron specific GFP reporters, we identified twelve genes
      required for the correct outgrowth of interneuron axons of the motor circuit. In
      mutant animals, axons fail to navigate correctly towards the ventral cord or fail
      to fasciculate correctly within the ventral cord. Several of those mutants define
      previously uncharacterized genes. Two of the genes, ast-4 and ast-7, are involved
      in the generation of left-right asymmetry of the two ventral cord axon tracts.
      Three other genes specifically affect pioneer-follower relationships between
      early and late outgrowing axons, controlling either differentiation of a pioneer
      neuron (lin-11) or the ability of axons to follow a pioneer (ast-2, unc-130).
      Navigation of the ventral cord pioneer neuron AVG itself is defective in ast-4,
      ast-6 and unc-130 mutants. Correlation of these defects with navigation defects
      in different classes of follower axons revealed a true pioneer role for AVG in
      the guidance of interneurons in the ventral cord. Taken together, these genes
      provide a basis to address different aspects of axon navigation within the
      ventral cord of C. elegans.

PMID- 15979605
TI  - Molecular interactions coordinating the development of the forebrain and face.
AB  - From an architectural point of view, the forebrain acts as a framework upon which
      the middle and upper face develops and grows. In addition to serving a structural
      role, we present evidence that the forebrain is a source of signals that shape
      the facial skeleton. In this study, we inhibited Sonic hedgehog (Shh) signaling
      from the neuroectoderm then examined the molecular changes and the skeletal
      alterations resulting from the treatment. One of the first changes we noted was
      that the dorsoventral polarity of the forebrain was disturbed, which manifested
      as a loss of Shh in the ventral telencephalon, a reduction in expression of the
      ventral markers Nkx2.1 and Dlx2, and a concomitant expansion of the dorsal marker
      Pax6. In addition to changes in the forebrain neuroectoderm, we observed altered
      gene expression patterns in the facial ectoderm. For example, Shh was not induced
      in the frontonasal ectoderm, and Ptc and Gli1 were reduced in both the ectoderm
      and adjacent mesenchyme. As a consequence, a signaling center in the frontonasal
      prominence was disrupted and the prominence failed to undergo proximodistal and
      mediolateral expansion. After 15 days of development, the upper beaks of the
      treated embryos were truncated, and the skeletal elements were located in more
      medial and proximal locations in relation to the skeletal elements of the lower
      jaw elements. These data indicate that a role of Shh in the forebrain is to
      regulate Shh expression in the face, and that together, these Shh domains mediate
      patterning within the frontonasal prominence and proximodistal outgrowth of the
      middle and upper face.

PMID- 15979606
TI  - Genetic redundancy in endoderm specification within the genus Caenorhabditis.
AB  - Specification of the endoderm precursor, the E cell, in Caenorhabditis elegans
      requires a genomic region called the Endoderm Determining Region (EDR). We showed
      previously that end-1, a gene within the EDR encoding a GATA-type transcription
      factor, restores endoderm specification to embryos deleted for the EDR and
      obtained evidence for genetic redundancy in this process. Here, we report
      molecular identification of end-3, a nearby paralog of end-1 in the EDR, and show
      that end-1 and end-3 together define the endoderm-specifying properties of the
      EDR. Both genes are expressed in the early E lineage and each is individually
      sufficient to specify endodermal fate in the E cell and in non-endodermal
      precursors when ectopically expressed. The loss of function of both end genes,
      but not either one alone, eliminates endoderm in nearly all embryos and results
      in conversion of E into a C-like mesectodermal precursor, similar to deletions of
      the EDR. While two putative end-1 null mutants display no overt phenotype, a
      missense mutation that alters a residue in the zinc finger domain of END-3
      results in misspecification of E in approximately 9% of mutant embryos. We report
      that the EDR in C. briggsae, which is estimated to have diverged from C. elegans
      approximately 50--120 myr ago, contains three end-like genes, resulting from both
      the ancient duplication that produced end-1 and end-3 in C. elegans, and a more
      recent duplication of end-3 in the lineage specific to C. briggsae. Transgenes
      containing the C. briggsae end homologs show E lineage-specific expression and
      function in C. elegans, demonstrating their functional conservation. Moreover,
      RNAi experiments indicate that the C. briggsae end genes also function
      redundantly to specify endoderm. We propose that duplicated end genes have been
      maintained over long periods of evolution, owing in part to their synergistic
      function.

PMID- 15979607
TI  - C. elegans HAM-1 positions the cleavage plane and regulates apoptosis in
      asymmetric neuroblast divisions.
AB  - Asymmetric cell division occurs when a mother cell divides to generate two
      distinct daughter cells, a process that promotes the generation of cellular
      diversity in metazoans. During Caenorhabditis elegans development, the asymmetric
      divisions of neural progenitors generate neurons, neural support cells and
      apoptotic cells. C. elegans HAM-1 is an asymmetrically distributed cortical
      protein that regulates several of these asymmetric neuroblast divisions. Here, we
      show that HAM-1 is a novel protein and define residues important for HAM-1
      function and distribution to the cell cortex. Our phenotypic analysis of ham-1
      mutant embryos suggests that HAM-1 controls only neuroblast divisions that
      produce apoptotic cells. Moreover, ham-1 mutant embryos contain many unusually
      large cell-death corpses. An investigation of this corpse phenotype revealed that
      it results from a reversal of neuroblast polarity. A misplacement of the
      neuroblast cleavage plane generates daughter cells of abnormal size, with the
      apoptotic daughters larger than normal. Thus, HAM-1 regulates the position of the
      cleavage plane, apoptosis and mitotic potential in C. elegans asymmetric cell
      divisions.

PMID- 15979608
TI  - Insulin induces internalization of the 5-HT2A receptor expressed in HEK293 cells.
AB  - To visualize the 5-hydroxytryptamine2A (5-HT2A) receptor, we developed a 5-HT2A
      receptor fused with yellow fluorescent protein (5-HT2A-YFP) and expressed this
      receptor in HEK293 cells. In 5-HT2A-YFP-expressing cells, but not in YFP
      expressing or non-expressing cells, 5-HT induced a transient increase in the
      intracellular Ca(2+) concentration (Ca(2+) transient) in the Fluo 3 assay,
      suggesting that 5-HT2A-YFP possesses a function similar to the wild-type 5-HT2A
      receptor. Interestingly, not only 5-HT but also insulin induced the
      internalization of 5-HT2A-YFP. Insulin also inhibited the 5-HT-induced Ca(2+)
      transient. Genistein, an inhibitor of tyrosine kinase, blocked these insulin
      effects. Our results provide the first evidence that insulin receptor signaling
      via tyrosine kinase activation induces internalization of the plasma membrane 5
      HT2A receptor, and demonstrate crosstalk between the 5-HT2A receptor and the
      insulin receptor.

PMID- 15979609
TI  - Adiponectin receptor 2 expression in liver and insulin resistance in db/db mice
      given a beta3-adrenoceptor agonist.
AB  - Our aim was to determine the effect of a beta3-adrenoceptor agonist on plasma
      adiponectin levels and on the level of expression of mRNA for adiponectin,
      adiponectin receptor 1, and adiponectin receptor 2 in db/db mice. Two weeks' oral
      administration of CL-316,243 led to decreased plasma levels of hemoglobin A1c,
      glucose, insulin, triglyceride and free fatty acid, and to an increased plasma
      adiponectin levels. It also improved insulin resistance in the oral glucose
      tolerance test. Adiponectin mRNA expression was significantly higher in the CL
      316,243-treatment group than in the control group in epididymal white adipose
      tissue but not in brown adipose tissue, soleus muscle or liver. Adiponectin
      receptor 2 mRNA expression was significantly lower only in the liver of the CL
      316,243-treatment group (versus the control group). These results suggest that
      the increased plasma adiponectin levels seen in db/db mice treated with this
      beta3-adrenoceptor agonist induce a down-regulation of adiponectin receptor 2
      mRNA expression specifically in the liver.

PMID- 15979610
TI  - Both apoptosis and complement membrane attack complex deposition are major
      features of murine acute graft-vs.-host disease.
AB  - The parent-into-F1 mouse model (P-->F1) of acute graft-vs.-host disease (GVHD) is
      a useful model of human acute GVHD because it allows the study of the T cell
      contribution to pathology without the complicating effects of conditioning
      regimens. To determine the similarity of this model to human GVHD, we assessed
      injury in organs typically involved in human acute GVHD (skin, liver) and less
      typically involved organs (spleen, kidney, lung). Mice were assessed
      histologically at early (2 weeks), intermediate (3 months) and late (6 month)
      time points. Based on the emerging roles of Fas ligand killing and complement
      deposition in allograft rejection, we correlated the amount of tissue specific
      TUNEL positive apoptosis and deposition of complement (C5b-9) with
      histopathologic changes. Our results indicate a striking similarity
      histologically between acute GVHD occurring in this model and in humans following
      bone marrow transplant. Moreover, C5b-9 deposition and apoptotic cell
      accumulation were found to parallel tissue injury in major organs of acute GVHD
      mice, although not all organs exhibited the same kinetic pattern. These results
      indicate a role for both adaptive immunity and innate immunity in this model of
      GVHD and support its use in modeling human acute GVHD in the nonmyeloablative
      setting.

PMID- 15979611
TI  - Immunolocalization of CYP1B1 in normal, human, fetal and adult eyes.
AB  - CYP1B1 is a cytochrome P450 enzyme implicated in autosomal recessive primary
      congenital glaucoma (PCG). The mechanism and function of CYP1B1 in the
      development of the PCG phenotype is unknown. Previously, investigators have
      reported detection of Cyp1b1 mRNA in the ciliary body and epithelium and
      neuroepithelium in the developing mouse eye, employing in situ hybridization
      techniques. Similarly, additional investigators have detected CYP1B1 mRNA in the
      iris, ciliary body, non-pigmented ciliary epithelial line, cornea, retinal
      pigment epithelium, and retina in the human adult eye, using Northern blotting.
      This study was designed to immunolocalize CYP1B1 protein in the various ocular
      structures of normal, human fetal and adult eyes. Normal fetal and adult eyes
      were immunolabeled with a polyclonal antibody against human CYP1B1 using indirect
      immunofluorescence, and then compared with appropriate controls. The intensity of
      immunolabeling of the various ocular structures was assessed by qualitative and
      semi-quantitative techniques. In the anterior segment anti-CYP1B1
      immunoreactivity (IR) was detected early in fetal development in the primitive
      ciliary epithelium. As well, the most intense CYP1B1 IR was in the non-pigmented
      ciliary epithelium. In addition, CYP1B1 IR was also present in the corneal
      epithelium and keratocytes, both layers of the iris pigmented epithelium, and
      retina. However, CYP1B1 IR was absent in the trabecular meshwork in all of the
      samples. In general, CYP1B1 immunolabeling in the human fetal eyes was more
      intense when compared to adult eyes. CYP1B1 IR was primarily immunolocalized to
      the non-pigmented ciliary epithelium and early in fetal development. In addition,
      CYP1B1 IR was not detected in the trabecular meshwork. These findings suggest
      that the abnormalities in the development of the trabecular meshwork in PCG may
      result from diminished or absent metabolism of important endogenous substrates in
      the ciliary epithelium due to non-functional CYP1B1 enzyme.

PMID- 15979612
TI  - Oxidative stress-induced retinal damage up-regulates DNA polymerase gamma and 8
      oxoguanine-DNA-glycosylase in photoreceptor synaptic mitochondria.
AB  - Bright light triggers biphasic photoreceptor nuclear DNA fragmentation,
      suggesting a DNA-repair response (Invest Ophthalmol Vis Sci 43:3511; 2002; Adv
      Med Biol 533:229-240; Mol Neurobiol 28:111-122). Here, we demonstrate a
      remarkable increase in expression of the mitochondrial DNA-repair enzymes, DNA
      polymerase gamma and 8-oxoguanine-DNA-glycosylase, following bright light
      treatment in rats. DNA polymerase gamma and 8-oxoguanine, the product of guanine
      oxidation, were selectively localized in photoreceptor synaptic terminals only
      within the superior central retinal region, where most light damage occurred. All
      induced DNA polymerase gamma was localized in photoreceptor synaptic terminals
      after 5 hr of light exposure, despite the fact that most photoreceptor cell
      mitochondria are confined to the inner segments. The neuroprotective platelet
      activating factor-receptor antagonist LAU-0901 decreased mitochondrial DNA
      polymerase gamma up-regulation, suggesting that its neuroprotective effect is
      exerted upstream from this event. During aging, the ability to repair damaged
      photoreceptor DNA greatly declines. Thus, DNA-repair enzymes such as polymerase
      gamma and 8-oxoguanine-DNA-glycosylase may provide novel pharmacologic targets to
      promote DNA repair and rescue photoreceptors in retinal degenerative diseases.

PMID- 15979613
TI  - Influence of sex on gene expression in the mouse lacrimal gland.
AB  - Significant, sex-associated differences exist in the physiology and
      pathophysiology of the lacrimal gland. We hypothesize that many of these
      differences are due to fundamental variations in gene expression. The purpose of
      this study was to determine the extent to which sex-related differences in gene
      expression are present in the lacrimal gland. Lacrimal glands were obtained from
      adult male and female BALB/c mice (n=5-10mice/sex/experiment), pooled according
      to sex and processed for the isolation of RNA. Samples were analyzed for
      differentially expressed mRNAs by using Atlas Mouse cDNA Expression Arrays, cDNA
      amplification techniques, GEM 1 and 2 gene chips, CodeLink bioarrays and
      quantitative real-time PCR (qPCR) procedures. Quantitative evaluation of Atlas
      Array gene expression was performed with an image analysis system developed in
      our laboratory, whereas gene chip data were analyzed with Rosetta Resolver and
      GeneSifter.Net software. Statistical significance was determined by using
      Student's t-test. Our results with CodeLink bioarrays show that sex has a
      significant influence on the expression of over 490 genes in the mouse lacrimal
      gland. These genes are involved in a wide range of biological processes,
      molecular functions and cellular components, including such activities as
      development, growth, transcription, metabolism, signal transduction, transport,
      receptor activity and protein and nucleic acid binding. The expression of
      selected genes was confirmed by the use of GEM gene chips and qPCR. Our findings
      also demonstrate that certain methodological approaches are less useful in
      attempting to assess the magnitude of sex-associated differences in the lacrimal
      gland. These results support our hypothesis that sex-related differences in gene
      expression play a role in the sexual dimorphism of the lacrimal gland.

PMID- 15979614
TI  - Setaria digitata: identification and characterization of a hypodermally expressed
      SXP/RAL2 protein.
AB  - SXP-1, an immunodominant filarial protein identified from Wuchereria bancrofti
      from our centre and previously exploited for diagnosis of human lymphatic
      filariasis, has been shown to be well conserved across several filarial species.
      In the present study, we describe the identification of SXP protein from the
      cattle filarid Setaria digitata using antiserum raised against recombinant WbSXP
      1, and were able to detect 34 and 66kDa proteins from the crude protein extracts
      of S. digitata. These reactive proteins were found to be sheath proteins
      localized to the hypodermal region of the parasite.

PMID- 15979615
TI  - Influence of synthesis and processing conditions on the release behavior and
      stability of sol-gel derived silica xerogels embedded with bioactive compounds.
AB  - The influence of processing parameters and synthetic strategies in the properties
      of sol-gel derived silica matrices intended for the release of bioactive
      compounds was investigated. The time-evolution of the matrix properties during
      its aging at room temperature in the dry and wet forms was investigated by
      measuring some of its physical and drug retaining properties. The results
      indicate that long term gel aging in the wet form is fundamental for the
      obtainment of dry matrices that are stable upon storage, a fundamental
      requirement for any practical application. In the case of hybrid matrices
      obtained by replacing part of the tetraethoxysilane precursor with mono-methyl
      trimethoxysilane, the order of addition of the reaction component is also
      important in determining the properties of the final dry gel, probably by
      influencing the polymer structural properties. This parameter acts
      synergistically with the matrix composition in determining the release properties
      of xerogels embedded with bioactive compounds.

PMID- 15979616
TI  - Effects of tank color on melanin-concentrating hormone levels in the brain,
      pituitary gland, and plasma of the barfin flounder as revealed by a newly
      developed time-resolved fluoroimmunoassay.
AB  - A pleuronectiform fish, the barfin flounder Verasper moseri, reared in a white
      tank had a smaller ratio of pigmented area of the skin on non-eyed side, grew
      faster, and had greater melanin-concentrating hormone (MCH)-immunoreactive cell
      bodies and MCH gene expression in the brain than in the black tank, indicating
      that synthesis and release of MCH are higher in fish from a white tank. In the
      present study, a time-resolved fluoroimmunoassay for MCH was developed. MCH
      levels were assessed in the brain, pituitary gland, and plasma of barfin
      flounders reared in a white or black tank. A competitive assay using two
      antibodies was performed among secondary antibodies in the solid phase, MCH
      antibodies, samples, and europium-labeled MCH. Displacement curves of serially
      diluted extracts (brain, pituitary gland, and plasma) of the barfin flounder
      paralleled that of the MCH standard. MCH levels in the brain and plasma were
      higher in fish reared in the white tank for 5 months than in the black tank.
      These results suggest that synthesis and secretion of MCH are enhanced with the
      white background and that MCH is involved in both somatic growth and the skin
      pigmentation in the barfin flounder.

PMID- 15979617
TI  - Structures for the proopiomelanocortin family genes proopiocortin and
      proopiomelanotropin in the sea lamprey Petromyzon marinus.
AB  - Gnathostomes express a common proopiomelanocortin (POMC) gene in the pars
      distalis (PD) and the pars intermedia (PI) of the pituitary gland. In contrast,
      the sea lamprey Petromyzon marinus expresses one distinct gene in each lobe;
      proopiocortin (POC) encoding adrenocorticotropic hormone (ACTH) and beta
      endorphin (END) is expressed in the PD and proopiomelanotropin (POM) encoding
      melanophore-stimulating hormone (MSH), and a different beta-END is expressed in
      the PI. We characterized the genomic structure of the sea lamprey POC and POM
      genes including their 5'-flanking regions. Both genes have two introns at
      positions similar to those of gnathostomes. Each exon encodes genetic information
      seen in the gnathostome POMC gene: exon 1 encodes an untranslated nucleotide
      sequence, exon 2 encodes a signal peptide and the N-terminal short part of POC or
      POM, and exon 3 encodes all other parts including ACTH, MSHs or beta-END. Intron
      A of POM (2289 bp) is six times longer than that of POC (379 bp). The POM intron
      A has three transposon-like sequences (TnL-1, -2, -3), the total length of which
      is 1781 bp, suggesting that it has expanded via the insertion of TnLs. The 5'
      flanking region of the POC gene contains two TATA boxes, a CCAAT box, eight E
      boxes, STAT, RAIE, and one binding site each for Ptx1, Pit-1, and Tpit. The POM
      gene contains four TATA boxes, eight E boxes, three STATs, two RAIEs, two CRE
      like elements, and one binding site for Pit1. However, there is virtually no
      similarity between the two genes in the distribution of the elements. The
      transcriptional regulation of POC and POM may have diverged with the functional
      differentiation of the two genes.

PMID- 15979618
TI  - Short term suppression of follicular recruitment and spontaneous ovulation in the
      cat using levonorgestrel versus a GnRH antagonist.
AB  - Suppression and subsequent rebound of ovarian activity using a progestin
      (levonorgestrel; Norplant) versus a GnRH antagonist (antide) was assessed in the
      domestic cat via fecal estradiol and progesterone metabolite analyses. Following
      an initial dose-response trial, queens were assigned to one of four treatments:
      (1) antide, two 6 mg/kg injections 15 days apart (n = 8 cats); (2)
      levonorgestrel, six silastic rods (36 mg levonorgestrel/rod) implanted for 30
      days (n = 8); (3) control injections (n = 5); and (4) control implants (n = 5).
      Steroid metabolites were quantified from daily fecal samples for 90 days before,
      30 days during, and 90 days after treatment. Antide and levonorgestrel inhibited
      estrous cyclicity in contrast to continued cyclicity in controls. Cats already at
      estradiol baseline in antide (n = 7) and levonorgestrel (n = 4) groups remained
      inhibited during treatment. In females with elevated estradiol levels at
      treatment onset (Day 0), a normal estradiol surge was completed before
      concentrations declined to baseline (approximately Days 5-7) and remained
      suppressed throughout the remaining treatment period. Additionally, 56% of
      treatment animals exhibited at least one spontaneous ovulation during the pre
      treatment period, but no female ovulated during treatment with levonorgestrel or
      antide. Antide-treated cats exhibited lower (P < 0.05) baseline estradiol
      concentrations during treatment compared to pre- and post-treatment. In contrast,
      levonorgestrel induced elevations in baseline estradiol following treatment
      compared to pre- and during treatment intervals. Control females showed no change
      (P > 0.05) in baseline estradiol throughout the study period. All levonorgestrel
      and antide cats returned to estrus after treatment withdrawal. Results
      demonstrate that: (1) both antide and levonorgestrel are effective for inducing
      short-term suppression of follicular recruitment and ovulation in the cat; (2)
      inhibition is reversible; and (3) GnRH antagonists and progestins differentially
      regulate basal estradiol secretion. This study also confirmed a relatively high
      incidence of spontaneous ovulation in the cat, a species generally considered to
      be an induced ovulator.

PMID- 15979619
TI  - Sequence, circulating levels, and expression of C-type natriuretic peptide in a
      euryhaline elasmobranch, Carcharhinus leucas.
AB  - The present study has examined expression and circulating levels of C-type
      natriuretic peptide (CNP) in the euryhaline bull shark, Carcharhinus leucas.
      Complementary DNA and deduced amino acid sequence for CNP in C. leucas were
      determined by RACE methods. Homology of CNP amino acid sequence in C. leucas was
      high both for proCNP and for mature CNP when compared with previously identified
      elasmobranch CNPs. Mature CNP sequence in C. leucas was identical to that in
      Triakis scyllia and Scyliorhinus canicula. Levels of expression of CNP mRNA were
      significantly decreased in the atrium but did not change in either the brain or
      ventricle following acclimation to a SW environment. However, circulating levels
      of CNP significantly increased from 86.0+/-7.9 fmol ml(-1) in FW to 144.9+/-19.5
      fmol ml(-1) in SW. The results presented demonstrate that changes in
      environmental salinity influences both synthesis of CNP from the heart and also
      circulating levels in C. leucas. Potential stimulus for release and modes of
      action are discussed.

PMID- 15979620
TI  - Commitment to relationships and preferences for femininity and apparent health in
      faces are strongest on days of the menstrual cycle when progesterone level is
      high.
AB  - Previous studies of changes in women's behavior during the menstrual cycle have
      offered insight into the motivations underpinning women's preferences for social
      cues associated with possible direct benefits (e.g., investment, low risk of
      infection) and indirect benefits (e.g., offspring viability). Here we sought to
      extend this work by testing for systematic variation in women's preferences for
      male and female faces and in their attitudes to their romantic relationship
      during the menstrual cycle. In Study 1, we found partnered women's reported
      commitment to their romantic relationship and preferences for femininity in male
      and female faces were strongest on days of the menstrual cycle when progesterone
      levels are increased (and fertility is low). Happiness in relationships did not
      change across the cycle. In Study 2, we found that the effect of cycle phase on
      women's preference for feminine faces was independent of increased attraction to
      apparent health in faces during the luteal phase. Collectively, these findings
      are further evidence that women's preferences for social cues associated with
      possible direct benefits and commitment to relationships are strongest during
      conditions characterized by raised progesterone level, while attraction to men
      displaying cues associated with possible indirect benefits is strongest when
      women are most fertile.

PMID- 15979621
TI  - Surgical and psychosocial outcomes in the rural injured--a follow-up study of the
      2001 earthquake victims.
AB  - INTRODUCTION: After a major disaster in a developing country, the graphic media
      coverage of the dead and injured invariably leads to an influx of volunteering
      healthcare personnel to the disaster zone. Very few studies document the outcomes
      of the treatment rendered in this field setting, under compromised conditions. We
      revisited the rural victims of the 2001 Gujarat earthquake in an attempt to
      analyse their surgical outcome and the status of their physical/psychosocial
      rehabilitation, 2 years after the disaster. METHOD: We traced displaced victims
      treated for earthquake-related injuries to their new homes. A community health
      worker interviewed patients with an oral questionnaire in the local language
      about injuries, the examining physician and first aid, orthopaedic implants,
      amputations, wounds, disability, deformity, residual pain, occupational and
      economic rehabilitation, post traumatic stress disorder (PTSD) and perceptions of
      healthcare rendered. RESULTS: We located 133 of the 179 non-urban victims, from
      11 villages. There were 10% missed injuries, 19% infection rate, restricted range
      of motion in 12%, non-union rate in 23% and reoperations in 30.5% patients. Fifty
      one percent had resumed their previous occupation, but only 30% had recovered
      economically. Of 98% who had destroyed homes, 89% had their homes rebuilt.
      Residual sadness was the only significant PTSD symptom. CONCLUSION: This trauma
      outcome study highlights the shortcomings of surgeons for disaster-related work.
      One-tenth of the injuries were missed, suggesting that field examination at the
      site of disaster was more difficult than in the comfort of the hospital emergency
      room. Further there were inappropriately timed, aggressive implant operations,
      short time commitments, a lack of follow-up and a high rate of reoperations
      contributing to subsequent morbidity. These pointed to a need for training in
      disaster medicine within the curriculum of surgical residency. On the brighter
      side, despite poor sterility, prolonged transport times and no prehospital care,
      the postoperative infection rate was lower than expected. This perhaps was due to
      use of potent antibiotics in a previously unexposed rural population. Good
      physiotherapy given in the temporary shelters, by the informal carers within the
      family and by voluntary groups, kept up a good range of motion and reduced the
      final disability. PTSD was marked 3-6 months after the event, but was minimal 2
      years postquake. Sadness about the event was the only residual PTSD symptom.
      While there were varying perceptions of satisfactory outcome, we found good
      coping mechanisms in place. The simple village folks were largely happy to be
      alive and accepted the residual deformities and cosmetic blemishes as a "small
      price to pay".

PMID- 15979622
TI  - Fixation of a complex comminuted proximal femoral fracture in the presence of a
      Birmingham hip resurfacing prosthesis.

PMID- 15979623
TI  - Bilateral occipital condyle fractures leading to retropharyngeal haematoma and
      acute respiratory distress.

PMID- 15979624
TI  - Outcome of routine bone scintigraphy in suspected scaphoid fractures.
AB  - Undisplaced scaphoid fractures are easily missed on conventional scaphoid
      radiographs, but these occult fractures may seriously impair hand function.
      Routine bone scintigraphy (BS) is often advocated if there are clinical signs of
      a scaphoid fracture without radiological evidence. However, the results require
      careful therapeutic management. OBJECTIVE: To determine the diagnostic value of
      BS in daily practice for clinically suspected scaphoid fractures. METHODS: We
      evaluated our protocol of routine BS in suspected scaphoid fractures. SUBJECTS:
      In a retrospective study, we analysed 111 consecutive cases with signs of a
      scaphoid fracture on physical examination. Radiographs revealed 55 fractures, the
      remaining 56 patients all underwent BS. MAIN RESULTS: On average, the BS was
      performed after 4 days. It showed a fracture in 38/56 of the patients. The
      distribution of fractures was: scaphoid bone 15, distal radius 11, other carpal
      bones 9 and metacarpal bones 3. CONCLUSION: If there is a strong clinical
      suspicion of a scaphoid fracture, which cannot be confirmed by conventional
      radiology, BS is a valuable diagnostic tool.

PMID- 15979625
TI  - Transitional fractures of the distal tibia.
AB  - INTRODUCTION: The purpose of the study was to determine the outcome after
      treatment of transitional fractures of the distal tibia, including growth
      disturbances, osteoarthritis, and/or restriction of the ability to take part in
      sports. PATIENTS AND METHODS: In a retrospective multicentre study of 72
      patients, 50 were evaluated by clinical and 46 by radiographic examination, an
      average of 7.4 years (standard deviation 5.9) after treatment. Of these 50
      patients, initially 20 were treated non-operatively and 30 were treated
      operatively. The mechanism was mainly supination trauma. RESULTS: There were four
      revision operations, including two for fracture displacement after earlier non
      operative treatment. No patients reported impairment of sports activities. In no
      case was the range of movement in the upper ankle joint decreased by >10 degrees
      . Radiographic examination revealed small osteophytes in one case and narrowing
      of the joint space in two; there was no axial deviation or clinical problems in
      any of these cases. There were no significant differences between the group
      treated non-operatively and the group that underwent surgery. The intermediate-
      to long-term outcome presented was good or very good in both the surgically and
      conservatively treated patients. Only two of the initially nondisplaced fractures
      later became displaced. This finding emphasises that operative treatment is not
      indicated for all nondisplaced fractures. Axial deviations may not occur, because
      of the little growth potential of the partially closed physis.

PMID- 15979626
TI  - The increasing burden of pelvic fractures in older people, New South Wales,
      Australia.
AB  - Despite their significant health burden, epidemiological information regarding
      pelvic fractures is scarce. In this study, we examine trends in admission for
      pelvic fractures to acute hospitals in New South Wales, Australia, between July
      1988 and June 2000, using routinely collected hospital separations statistics.
      Over this period, the number of admissions for pelvic fractures among those aged
      50 years and over increased by 58.4% in men and 110.8% in women. Age-specific
      rates of admissions per 100,000 population for pelvic fracture also rose
      significantly, particularly for those aged at least 75 years. The number and
      proportion of transport related pelvic fractures fell significantly for both men
      (chi(2)=23.82, d.f.=1, p<0.001) and women (chi(2)=49.26, d.f.=1, p<0.001) while
      those resulting from falls increased significantly over the 12-year-period. Falls
      are increasingly becoming the single most important cause of pelvic injuries in
      older people, suggesting that preventive measures aimed at reducing the risk of
      falls need to be pursued. Factors contributing to the rise of fall-related pelvic
      fractures need to be investigated to inform strategies aimed at reversing the
      observed increase in the number and age-specific rates of pelvic fractures in
      older people.

PMID- 15979627
TI  - 'Making it better': self-perceived roles of family caregivers of older people
      living in care homes: a qualitative study.
AB  - BACKGROUND: With growing numbers of frail older people making the move to a care
      home, family carers are increasingly finding themselves in the position of
      assisting with this transition and establishing a new caring role within this
      context. However, the nature of the family caregiving role within the care home
      setting is poorly understood. AIMS AND OBJECTIVES: This paper draws on data from
      a study, which sought to better understand the experience of nursing home
      placement from the viewpoint of relatives. The focus here is on the self
      perceived contribution of family carers to life within the home. METHODS: A
      constructivist methodology was used. Data were collected in 37 semi-structured
      interviews involving 48 people who had assisted a close relative to move into a
      care home. FINDINGS: Data analysis revealed three phases to the transition from
      the relatives' perspective. This paper reports on the findings which relate to
      the final phase: 'making it better', which documents experiences of establishing
      a new caregiving role within the care home. Relatives described three main
      aspects to their role: maintaining continuity, which involves helping the older
      person to maintain their sense of identity through the continuation of loving
      family relationships and through helping staff to get to know the resident as an
      individual; keeping an eye, by monitoring the care received, providing feedback
      to staff and filling any gaps, and contributing to community through interacting
      with other residents, relatives and staff, taking part in social events and
      generally providing a link with the outside world. RELEVANCE TO CLINICAL
      PRACTICE: Findings suggest that the potential contribution of relatives to
      promoting the well-being of both residents and staff is under-developed. Staff in
      care homes should seek to identify the role that relatives would like to perform
      and support them to achieve this.

PMID- 15979628
TI  - Fatal experimental transplacental Babesia gibsoni infections in dogs.
AB  - A Babesia gibsoni infected bitch was mated with an uninfected dog in order to
      determine whether this parasite could be vertically transmitted. The bitch
      delivered a litter of four live and one stillborn pup. The four pups died from
      congenital babesiosis between 14 and 39 days post-birth. Babesia gibsoni DNA was
      detected in tissue from all five pups. These results show that vertical
      transmission occurred by the uterine route and not via the transmammary route.
      This is the first confirmed report of transplacental Babesia infection in any
      animal species.

PMID- 15979630
TI  - The effect of the physical and chemical characteristics of activated carbons on
      the adsorption energy and affinity coefficient of Dubinin equation.
AB  - The dependency of adsorption energy (E) and affinity coefficient (beta) of
      Dubinin equations (Dubinin-Radushkevich (DR) or Dubinin-Astakhov (DA)) on surface
      chemistry and porosity of activated carbons was investigated by analyzing
      adsorption of nitrogen, benzene, trichloroethylene (TCE), and water vapor by
      several surface-modified activated carbons and carbon fibers. For all studied
      nonpolar adsorbates, carbons with smaller average micropores showed higher
      adsorption energies independent of their surface chemistry. For water vapor,
      carbons with higher surface polarities showed higher adsorption energies due to
      specific adsorbate-adsorbent interactions. Adsorption energies increased with
      decreasing average micropore widths. betaN2,DR for different carbons were
      observed to vary in the 0.292-0.539 range. Carbons with higher degrees of
      mesoporosity had higher betaN2,DR values, while no dependency was observed
      between betaN2,DR and surface chemistry. A comparison of DR and DA cases
      indicates that: (1) the average value of betaN2,DA is considerably above the
      classical value of this parameter; and (2) the range of betaN2,DA values were
      smaller compared to betaN2,DR, despite a wide range of mesoporosity of carbons
      examined. Obtained beta(TCE,DR) values varied in the 0.952-1.243 range, with an
      average value of 1.085+/-0.083, independent of surface chemistry or porosity of
      activated carbons. A similar result was observed for beta(TCE,DA). betaH2O,DR
      values of different granular and fibrous activated carbons changed in the range
      of 0.081-0.271. They depended more on the carbon surface chemistry and less on
      the porosity. A similar result was obtained when DA equation was considered.

PMID- 15979629
TI  - Role of the macrophage very-low-density lipoprotein receptor in atherosclerotic
      lesion development.
AB  - OBJECTIVES: The very-low-density lipoprotein receptor (VLDLr) is highly expressed
      in macrophage-rich areas of atherosclerotic lesions. The exact role of the
      macrophage VLDLr in atherosclerotic lesion development, however, is presently
      unclear. METHODS AND RESULTS: To assess the role of the macrophage VLDLr in
      atherosclerotic lesion development in vivo, we used the technique of bone marrow
      transplantation to selectively disrupt or reconstitute the VLDLr in macrophages
      in VLDLr+/+ and VLDLr-/- mice, respectively. After 10 weeks high-cholesterol diet
      feeding, the lesion area in control transplanted wild-type mice was 17+/-4 x
      10(3)+/-microm(2). Disruption of the macrophage VLDLr by transplanting bone
      marrow from VLDLr-/- mice to wild-type VLDLr+/+ littermates resulted in a
      tendency to a slight reduction in lesion size to 12+/-3 x 10 microm. The mean
      atherosclerotic lesion area, measured in control transplanted VLDLr-/- mice,
      lacking the VLDLr in all tissues was 12+/-3 x 10(3)microm(2). Interestingly,
      reconstitution of the macrophage VLDLr in VLDLr-deficient recipients resulted in
      a 2.7-fold increase (P<0.05) in the mean atherosclerotic lesion area to 32+/-3 x
      10(3)microm(2). CONCLUSIONS: The macrophage VLDLr facilitates atherosclerotic
      lesion development, probably by mediating the accumulation of atherogenic
      lipoproteins.

PMID- 15979631
TI  - A thermodynamic approach for determining the contact angle hysteresis for
      superhydrophobic surfaces.
AB  - Contact angle hysteresis (CAH) is critical to superhydrophobicity of a surface.
      This study proposes a free energy thermodynamic analysis (of a 2-D model surface)
      that significantly simplifies calculations of free energy barrier associated with
      CAH phenomena. A microtextured surface with pillar structure, typical of one used
      in experimental studies, is used as an example. We demonstrate that the predicted
      CAH and equilibrium contact angles are consistent with experimental observations
      and predictions of Wenzel's and Cassie's equations, respectively. We also
      establish a criterion for transition between noncomposite and composite wetting
      states. The results and methodology presented can potentially be used for
      designing superhydrophobic surfaces.

PMID- 15979632
TI  - Solubility of sodium soaps in aqueous salt solutions.
AB  - The solubility of sodium soaps in dilute aqueous salt solutions has been
      systematically investigated by direct visual phase behavior observations. The
      added electrolytes, including simple inorganic salts and bulky organic salts,
      influence the solubility of sodium soaps in water, as represented by the varied
      soap Krafft point. Two inorganic salts, sodium chloride and sodium perchlorate,
      demonstrate a "salting-out" property. On the other hand, tetraalkylammonium
      bromides show an excellent ability to depress the soap Krafft point and enhance
      the soap solubility in water. With increasing the tetraalkylammonium ionic size,
      the degree of "salting-in" of soaps in water increases. However, solubility of
      pure tetraalkylammonium bromide in water decreases as the length of the alkyl
      chains increases. Furthermore, in the ternary water-tetrapentylammonium bromide
      (TPeAB)-sodium myristate (NaMy) system, we observed an upper cloud point
      phenomenon, which greatly shrinks the 1-phase micellar solution region in the
      phase diagram. This miscibility gap, together with the organic salt solubility
      limitation, restricts the use of tetraalkylammonium bromides with alkyl chains
      longer than 4 carbon atoms as effective soap solubility enhancement electrolytes.
      We also found that for sodium soap with a longer hydrocarbon chain, more
      tetrabutylammonium salt is required to reduce the soap Krafft point to room
      temperature.

PMID- 15979633
TI  - Effect of sodium dodecylbenzene sulfonate on the motion of three-phase contact
      lines on the Wilhelmy plate surface.
AB  - The combined approach of the molecular-kinetic and hydrodynamic theories for
      description of the motion of three-phase gas-liquid-solid contact lines has been
      examined using the Wilhelmy plate method. The whole dynamic meniscus has been
      divided into molecular, hydrodynamic, and static-like regions. The Young-Laplace
      equation and the molecular-kinetic and hydrodynamic dewetting theories have been
      applied to describe the meniscus profiles and contact angle. The dissipative
      forces accompanying the dynamic dewetting have also been investigated. The
      experiments with a Wilhelmy plate made from an acrylic polymer sheet were carried
      out using a computerized apparatus for contact angle analysis (OCA 20,
      DataPhysics, Germany). The extrapolated dynamic contact angle versus velocity of
      the three-phase contact line for Milli-Q water and 5x10(-4) M SDBS solution was
      experimentally obtained and compared with the combined MHD models with low and
      moderate Reynolds numbers. The models predict similar results for the
      extrapolated contact angle. SDBS decreases the equilibrium contact angle and
      increases the molecular jumping length but does not affect the molecular
      frequency significantly. The hydrodynamic deformation of the meniscus, viscous
      dissipation, and friction were also influenced by the SDBS surfactant.

PMID- 15979634
TI  - Lead biosorption study with Rhizopus arrhizus using a metal-based titration
      technique.
AB  - Acid-base and metal-based potentiometric titration methods were used to analyze
      sorption mechanisms of lead by Rhizopus arrhizus fungal biomass. Biosorption was
      not considered globally but as the result of successive sorption reactions on
      various binding sites with different selectivities. Precipitation occurred
      rapidly when lead concentration increased. Lead was sorbed essentially by
      carboxylic groups and by phosphates and sulfonates (less abundant) of the organic
      matter. The lead affinity to carboxylic, sulfonate and phosphate binding sites
      depended on the association coefficient with proton or counter-ion and on the
      spatial distribution of the surface sites promoting the formation of mono- or bi
      dentate complexes. Chemical bonds and binding sites were confirmed using
      microscopic and spectroscopic techniques (IR, MET-EDAX). It appeared that
      although the total organic acidity was reached, number of ionized and free
      carboxylic groups were not involved in lead sorption reactions. In spite of lead
      speciation in the solution, surface micro-precipitation was observed and the two
      processes, surface adsorption and micro-precipitation, are sequential and
      possibly overlapping. At low concentrations (<10(-6) M) adsorption is the
      dominant phenomenon and beyond (>10(-5) M) surface clusters appeared before the
      predicted solution precipitation phenomenon.

PMID- 15979635
TI  - Clinical management of a child with Prader-Willi Syndrome from maternal
      uniparental disomy (UPD) genetic inheritance.
AB  - Prader-Willi Syndrome (PWS) is reported in 1 in 10,000-15,000 individuals.
      Unfortunately, many cases are missed due to clinicians' lack of familiarity with
      the syndrome as well as clinical and laboratory diagnostic criteria. Although
      common clinical characteristics are reported, variety exists in the nature and
      severity of dysfunction associated with PWS. Case studies can provide information
      to understand relationships between phenotypic characteristics and genetic
      inheritance, which can in turn lead to effective clinical management. The purpose
      of this case study was to describe the characteristics of a child with PWS due to
      maternal uniparental disomy inheritance pattern and to describe clinical
      management and treatment outcomes. LEARNING OUTCOMES: The reader will obtain
      information about: (1) the genetic inheritance patterns and clinical
      characteristics of Prader-Willi Syndrome, (2) genotypic/phenotypic relationships
      specific to Prader-Willi Syndrome, and (3) clinical implications, management, and
      outcomes in a case description of a child with PWS due to maternal uniparental
      disomy inheritance pattern.

PMID- 15979636
TI  - Development of detection methods for ruminant interleukin (IL)-4.
AB  - Recombinant bovine IL-4 (rbo IL-4) was transiently expressed in COS-7 cells. Mice
      were immunised with a plasmid encoding rbo IL-4 and boosted with rbo IL-4. A
      number of monoclonal antibodies (mAb) were generated that reacted with rbo IL-4
      in an ELISA and these cloned hybridomas were termed CC311, CC312, CC313 and
      CC314. A pair of mAb (CC313 and CC314) was identified that together could be used
      to detect both recombinant and native bovine IL-4 by ELISA and a luminometric
      detection method was applied to the ELISA. Using this method native bovine IL-4
      was detected in supernatants of PBMC stimulated with mitogens. In addition, high
      level secretion of IL-4 by Fasciola hepatica specific Th2 clones, but not by a
      Babesia bovis specific Th1 clone, was confirmed. The ELISA was also able to
      detect recombinant ovine IL-4. The pair of mAb used for ELISA could also be used
      for the detection of IL-4 spot forming cells by ELISPOT. In addition
      intracytoplasmic expression of IL-4 could be detected. The ability to detect
      ruminant IL-4 by three methods: ELISA, ELISPOT and by flow cytometric analysis of
      intracytoplasmic expression will permit studies of the role of this important
      cytokine in the immunology and pathogenesis of animal diseases.

PMID- 15979637
TI  - Comparison of electrochemiluminescence assay and ELISA for the detection of
      Clostridium botulinum type B neurotoxin.
AB  - We compared the ELISA and electrochemiluminescence (ECL) immunoassay technologies
      for the detection of botulinum type B neurotoxin (BotNT B), which requires highly
      sensitive techniques due to its potent biological activity. BotNT B complexes are
      the naturally secreted form of the toxin, approximately a third of which consists
      of the neurotoxin itself; they were aliquoted and frozen for this study. Results
      of both techniques were interpreted with the same standard statistical tests
      (ANOVA and Tukey). We first compared two commercial assays for BotNT B: the
      detection limit of the colorimetric ELISA was 1.56 ng/ml BotNT B complexes versus
      0.39-0.78 ng/ml in the ECL test. We then used the same monoclonal antibody and
      the same polyclonal antibody, respectively purified by protein A and protein G
      chromatography, to optimize an in-house ELISA test and an in-house ECL test,
      making it possible to directly compare the two technologies without interference
      due to the properties of the antibodies used in the two tests. The colorimetric
      in-house ELISA had a detection threshold of 3.12 ng/ml versus the in-house ECL
      test whose detection threshold was 0.78-1.56 ng/ml. Thus, in both cases, the ECL
      assay was two to four times more sensitive than the colorimetric ELISA. The ECL
      assay was also more rapid (2.5 h for the in-house ECL versus 5 h for in-house
      ELISA with precoated wells). Overall, these elements can be used to compare the
      qualities of the two technologies, at least for the detection of protein antigens
      such as toxins.

PMID- 15979638
TI  - A multiplexed and miniaturized serological tuberculosis assay identifies antigens
      that discriminate maximally between TB and non-TB sera.
AB  - We have developed a multiplexed and miniaturized TB serological assay with the
      aim of identifying (combinations of) antigens that maximally discriminate between
      TB and non-TB patients. It features a microarray accommodating 54 TB antigens,
      less than 1 microl serum consumption and an indirect immunofluorescence detection
      protocol. With a panel of 20 TB and 80 non-TB sera we ranked combinations of TB
      antigens with respect to sensitivity and specificity of TB detection by means of
      logistic step-forward regression analysis. The highest-ranking TB antigen
      combination had an area-under-the-curve of the receiver-operator-characteristics
      (ROC) of 0.95. We also identified an antigen that on its own provided good
      specificity and sensitivity of TB detection (Ara6-BSA; area-under-the-ROC curve:
      0.90). These area-under-the-ROC curve values are exceptionally high for a
      serological TB assay. We conclude that TB antigen microarrays permit rapid
      identification of TB antigens that, either alone or in combination, discriminate
      maximally between TB and non-TB patients and that such identification provides an
      excellent starting point for developing point-of-care diagnostic assays.

PMID- 15979639
TI  - Diapause and biological clocks: introduction.

PMID- 15979640
TI  - Two groups of entomopathogenic bacteria, Photorhabdus and Xenorhabdus, share an
      inhibitory action against phospholipase A2 to induce host immunodepression.
AB  - Photorhabdus and Xenorhabdus are two genera of entomopathogenic bacteria having a
      mutualistic relationship with their respective nematode hosts, Heterorhabditis
      and Steinernema. One of the pathogenic mechanisms of these bacteria includes host
      immunodepression, which leads to lethal septicemia. It has been known that X.
      nematophila inhibits phospholipase A2 (PLA2) to induce host immunodepression.
      Here, we tested the hypothesis of PLA2 inhibition using another bacterial species
      involved in other genera. P. temperata subsp. temperata is the intestinal
      symbiont of an entomopathogenic nematode, H. megidis. The bacteria caused potent
      pathogenicity in a dose-dependent manner against the fifth instar larvae of a
      test target insect, Spodoptera exigua, as early as 24 h after the intra
      hemocoelic injection. In response to the live bacterial injection, hemocyte
      nodulation (a cellular immune response) and prophenoloxidase (pPO) activation
      were inhibited, while the injection of heat-killed bacteria significantly induced
      both immune reactions. The immunodepression induced by the live bacteria was
      reversed by the addition of arachidonic acid, the catalytic product of
      phospholipase A2. In contrast, the addition of dexamethasone, a specific PLA2
      inhibitor to the heat-killed bacterial treatment, inhibited both immune
      capacities. In addition to a previously known PLA2 inhibitory action of X.
      nematophila, the inhibition of P. temperata temperata on PLA2 suggests that
      bacteria symbiotic to entomopathogenic nematodes share a common pathogenic target
      to result in an immunodepressive state of the infected insects. To prove this
      generalized hypothesis, we used other bacterial species (X. bovienni, X.
      poinarii, and P. luminescens) involved in these two genera. All our experiments
      clearly showed that these other bacteria also share their inhibitory action
      against PLA2 to induce host immunodepression.

PMID- 15979641
TI  - The response regulator OmpR oligomerizes via beta-sheets to form head-to-head
      dimers.
AB  - In Escherichia coli, the EnvZ/OmpR two-component regulatory system regulates
      expression of the porin genes ompF and ompC in response to changes in osmolarity.
      It has recently become apparent that OmpR functions as a global regulator, by
      regulating the expression of many genes in addition to the porin genes. OmpR
      consists of two domains; phosphorylation of the N-terminal receiver domain
      increases DNA binding affinity of the C-terminal domain and vice versa. Many
      response regulators including PhoB and FixJ dimerize upon phosphorylation. Here,
      we demonstrate that OmpR dimerization is stimulated by phosphorylation or by DNA
      binding. The dimerization interface revealed here was unanticipated and had
      previously not been predicted. Using the accepted head-to-tail tandem-binding
      model as a guide, we set out to examine the intermolecular interactions between
      OmpR dimers bound to DNA by protein-protein cross-linking methods. Surprisingly,
      amino acid positions that we expected to form cross-linked dimers did not.
      Conversely, positions predicted not to form dimers did. Because of these results,
      we designed a series of 23 cysteine-substituted OmpR mutants that were used to
      investigate dimer interfaces formed via the beta-sheet region. This four-stranded
      beta-sheet is a unique feature of the OmpR group of winged helix-turn-helix
      proteins. Many of the cysteine-substituted mutants are dominant to wild-type
      OmpR, are phosphorylated by acetyl phosphate as well as the cognate kinase EnvZ,
      and the cross-linked proteins are capable of binding to DNA. Our results are
      consistent with a model in which OmpR binds to DNA in a head-to-head orientation,
      in contrast to the previously proposed asymmetric head-to-tail model. They also
      raise the possibility that OmpR may be capable of adopting more than one
      orientation as it binds to a vast array of genes to activate or repress
      transcription.

PMID- 15979642
TI  - Repetitive pulling catalyzes co-translocational unfolding of barnase during
      import through a mitochondrial pore.
AB  - We present a computational study of barnase unfolding during import into
      mitochondria through a model translocon. In contrast to thermal (or chemical)
      unfolding, the major intermediates of co-translocational unfolding are mainly
      mediated by non-native interactions accompanying the protein configurations
      induced by pulling forces. These energy contributions, combined with backbone
      topological constraints imposed by the model pore, result in milestones along the
      unfolding pathways which are significantly different not only from those
      experienced during thermal (or chemical) denaturation, but also from those
      observed in single-molecule pulling by both ends without pore constraints. Two on
      pathway major translocation intermediates trapped in long-lived states by
      significantly high unfolding barriers are identified. A fraction of these
      pathways can, however, skip such local kinetic traps and result in extremely fast
      translocations, leading to a dramatic kinetic partitioning spanning approximately
      four orders of magnitude. The fraction of fast translocation events is shown to
      increase upon switching the pull off and on, when compared to pulling at constant
      force. This suggests a "catalytic" mechanism by which the mitochondrial import
      machinery regulates this partitioning by repetitively pulling in cycles. A number
      of mutation sites that alter the kinetic "flow" of the unfolding trajectories are
      suggested and tested.

PMID- 15979643
TI  - Validation of an IVRS version of the MADRS.
AB  - Interest in self-reported measures of depression in clinical trials has grown in
      recent years. This study compared the reliability and validity of the clinician
      administered Montgomery-Asberg Depression Rating Scale (MADRS) to a computer
      administered version administered over the telephone using Interactive Voice
      Response (IVR) technology. Sixty subjects were administered both the clinician-
      and computer-administered versions of the MADRS in a counter-balanced order. A
      subsample of 20 patients was reassessed 24h later by both methods. Mean score
      differences between IVR and clinician were not statistically significant (<1
      point) and a high correlation was found between forms (r=.815, p<.001).
      Reliability measures (Cronbach's Alpha and 24-h test-retest) were comparable.
      Clinicians rated the severity of subjects' sadness and pessimistic thoughts lower
      than subjects self-report. The data obtained in this pilot study provide support
      for the equivalence between the clinician and IVR versions of the MADRS.

PMID- 15979644
TI  - The relationship between eye movement and brain structural abnormalities in
      patients with schizophrenia and their unaffected relatives.
AB  - Schizophrenia is associated with subtle eye movement and brain structural
      abnormalities, but the extent to which these abnormalities occur in the same
      individuals is unclear. The relationship between quantitative measures of eye
      movement task performance (smooth pursuit and antisaccade) and MRI volumetric
      measurements (whole brain volume, prefrontal region, lateral ventricles, third
      ventricle, hippocampus, and cerebellum) was assessed in 70 patients with
      schizophrenia or schizoaffective disorder, 105 of their unaffected first-degree
      relatives and 68 controls. There was a lack of correlation between eye movement
      and morphometric abnormalities suggesting largely separable neurobiological
      pathways underlying the morphological and the eye movement deviations that have
      previously been identified in these patients. However, in the total sample,
      smaller prefrontal lobe volume was significantly associated with longer latency
      of correct antisaccades (partial correlation r=-0.22, p=0.01) in line with
      previous studies demonstrating the importance of frontal lobe structures in
      performance of the antisaccade task. Also larger third ventricular volume was
      associated with larger mean amplitude of intrusive saccades during smooth pursuit
      (r=0.28, p=0.01). There were no significant between-group differences in the
      relationship between measures of eye movement and morphometry.

PMID- 15979646
TI  - Ischemic symptoms induced by occlusion of the unilateral vertebral artery with
      head rotation together with contralateral vertebral artery dissection--case
      report.
AB  - We report a 45-year-old woman whose unilateral vertebral artery (VA) was
      potentially occluded with head rotation at the C1-C2 level and her ischemic
      symptoms suddenly appeared because of contralateral VA dissection. She noticed
      first pain around the posterior part of her neck on the right side, and then
      dizziness when turning the head to the right side. The dizziness disappeared
      immediately after her head returned to the natural position. Digital subtraction
      angiography (DSA) showed a string sign of the right VA. DSA and computed
      tomography angiography (CTA) showed high grade extrinsic compression of the left
      VA at the C1-C2 level with head rotation more than 90 degrees to the right. Three
      dimensional (3D) CTA also showed clearly kinking of the left VA at the C2
      neuroforamina. Her symptoms disappeared completely with conservative therapy, and
      recanalization of the right VA was also confirmed by 3D-CTA. 3D-CTA was thought
      to be valuable to diagnose and manage the rotational compression of the artery.
      VA dissection must be remembered to differentially diagnose the etiology of
      transient attacks of posterior circulation ischemia due to rotational
      contralateral VA occlusion.

PMID- 15979648
TI  - Spinocerebellar ataxia type 6 in Mainland China: molecular and clinical features
      in four families.
AB  - The hereditary spinocerebellar ataxias (SCAs) are a clinically and genetically
      heterogeneous group of neurodegenerative disorders. The genes causing 11 of these
      diseases have been identified. To date, there is no report of SCA type 6 (SCA6)
      in Mainland Chinese. Using a molecular approach, we investigated SCA6 as well as
      other SCA subtype in 120 Mainland Chinese families with dominantly inherited
      ataxias and in 60 Mainland Chinese patients with sporadic ataxias. Clinical and
      molecular features of SCA6 were further characterized in 13 patients from 4
      families. We found that SCA3/MJD was the most common type of autosomal dominant
      SCA in Mainland Chinese, accounting for 83 patients from 59 families (49.2%),
      followed by SCA2 (8 [6.7%]), SCA1 (7 [5.8%]), SCA6 (4 [3.3%]), SCA7 (1 [0.8%]),
      SCA8 (0%), SCA10 (0%), SCA12 (1 [0.8%]), SCA14 (0%), SCA17 (0%) and DRPLA (0%).
      The genes responsible for 40 (33.3%) of dominantly inherited SCA families remain
      to be determined. Among the 60 patients with sporadic ataxias in the present
      series, 3 (5.0%) were found to harbor SCA3 mutations, whereas none were found to
      harbor SCA6 mutations. In the 4 families with SCA6, we found significant
      anticipation in the absence of genetic instability on transmission. This is the
      first report of geographic cluster of families with SCA6 subtype in Mainland
      China.

PMID- 15979649
TI  - Dynamical and cellular electrophysiological mechanisms of ECG changes during
      ischaemia.
AB  - The interpretation of normal and pathological electrocardiographic (ECG) patterns
      in terms of the underlying cellular and tissue electrophysiology is rudimentary,
      as the existing theories rely on geometrical aspects. We relate effects of sub
      endocardial ischaemia on the ST-segment depression in ECG to patterns of
      transmural action potential propagation in a one-dimensional virtual ventricular
      wall. Our computational study exposes two electrophysiological mechanisms of ST
      depression: dynamic-predominantly positive spatial gradients in the membrane
      potential during abnormal repolarization of the wall, produced by action
      potential duration changes in the ischaemic region; and static-a negative spatial
      gradient of the resting membrane potential between the normal and ischaemic
      regions. Hyperkalaemia is the major contributor to both these mechanisms at the
      cellular level. These results complement simulations of the effects of cardiac
      geometry on the ECG, and dissect spatio-temporal and cellular
      electrophysiological mechanisms of ST depression seen in sub-endocardial
      ischaemia.

PMID- 15979650
TI  - A model of the dynamics of insect cell infection at low multiplicity of
      infection.
AB  - In the present paper, we offer a preliminary mathematical model that describes
      the dynamic process of cell infection with baculovirus at low multiplicity of
      infection (MOI). The model accounts for the chain of events that follow the
      infection of insect cells, namely the eclipse period, the budding of viral
      particles from those cells, their attachment to non-infected cells and the
      initiation of a new infection cycle. These cycles appear as fluctuations in the
      viral concentration of actual cell culture media. The potential of the present
      approach in simulating the in vitro production of biological insecticides is
      demonstrated. The influence of the shape of the virus-budding function is shown,
      and parameter sensitivity analysis is carried out. The model provides a
      quantitative tool for the analysis of this complex dynamic system.

PMID- 15979645
TI  - Functional brain imaging of tobacco use and dependence.
AB  - While most cigarette smokers endorse a desire to quit smoking, only about 14% to
      49% will achieve abstinence after 6 months or more of treatment. A greater
      understanding of the effects of smoking on brain function may (in conjunction
      with other lines of research) result in improved pharmacological (and behavioral)
      interventions. Many research groups have examined the effects of acute and
      chronic nicotine/cigarette exposure on brain activity using functional imaging;
      the purpose of this paper is to synthesize findings from such studies and present
      a coherent model of brain function in smokers. Responses to acute administration
      of nicotine/smoking include: a reduction in global brain activity; activation of
      the prefrontal cortex, thalamus, and visual system; activation of the thalamus
      and visual cortex during visual cognitive tasks; and increased dopamine (DA)
      concentration in the ventral striatum/nucleus accumbens. Responses to chronic
      nicotine/cigarette exposure include decreased monoamine oxidase (MAO) A and B
      activity in the basal ganglia and a reduction in alpha4beta2 nicotinic
      acetylcholine receptor (nAChR) availability in the thalamus and putamen. Taken
      together, these findings indicate that smoking enhances neurotransmission through
      cortico-basal ganglia-thalamic circuits either by direct stimulation of nAChRs,
      indirect stimulation via DA release or MAO inhibition, or a combination of these
      factors. Activation of this circuitry may be responsible for the effects of
      smoking seen in tobacco dependent subjects, such as improvements in attentional
      performance, mood, anxiety, and irritability.

PMID- 15979651
TI  - Mutation in evolutionary games can increase average fitness at equilibrium.
AB  - We study game dynamical interactions between two strategies, A and B, and analyse
      whether the average fitness of the population at equilibrium can be increased by
      adding mutation from A to B. Classifying all two by two games with payoff matrix
      [(a,b),(c,d)], we show that mutation from A to B enhances the average fitness of
      the whole population (i) if both a and d are less than (b + c)/2 and (ii) if c is
      less than b. Furthermore, we study conditions for maximizing the productivity of
      strategy A, and we analyse the effect of mutations in both directions. Depending
      on the biological system, a mutation in an evolutionary game can be interpreted
      as a genetic alteration, a cellular differentiation, a change in gene expression,
      an accidental or deliberate modification in cultural transmission, or a learning
      error. In a cultural context, our results indicate that the equilibrium payoff of
      the population can be increased if players sometimes choose the strategy with
      lower payoff. In a genetic context, we have shown that for frequency-dependent
      selection mutation can enhance the average fitness of the population at
      equilibrium.

PMID- 15979652
TI  - Naltrexone plus benzodiazepine aids abstinence in opioid-dependent patients.
AB  - Naltrexone (NTX) is widely used to prevent relapse of opioid-dependent patients
      but its association with insomnia and "hyperexcitability" can result in treatment
      withdrawal. We evaluated whether NTX combined with the benzodiazepine prazepam
      was more effective than NTX in keeping patients opioid-free. We determined the
      relapse rate over 6 months in 56 opioid-dependent subjects, divided into 4 equal
      groups. All groups received psychological support and underwent urine tests for
      drug metabolites twice weekly. Group 1 did not receive pharmacological treatment
      (controls). Group 2 received NTX alone (one 50-mg tablet daily); group 3 received
      NTX (one 50-mg tablet daily) plus placebo (one tablet twice daily); and group 4
      received NTX (one 50-mg tablet daily) plus prazepam (one 10-mg tablet twice
      daily). Ten patients of group 1 relapsed within 3 months, one after 6 months and
      three remained opioid-free. Six patients of group 2 relapsed within three months,
      two after 6 months, and six remained opioid-free. Seven patients of group 3
      relapsed three months, one after 6 months and six patients remained opioid-free.
      In group 4, one patient relapsed within 3 months and one patient after 6 months;
      12 patients of this group remained opioid-free. At urine tests, a significantly
      higher percent patients of group 4 remained free of Delta(9)-tetrahydrocannabinol
      versus patients of groups 2 and 3. In conclusion, many patients remained opioid
      free on NTX alone or combined with prazepam, with a significant advantage for the
      NTX plus prazepam group.

PMID- 15979653
TI  - Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated
      Kupffer cells.
AB  - Leptin is now recognized as a proinflammatory cytokine and thought to be a
      progressive factor for non-alcoholic steatohepatitis (NASH). Here we showed the
      effects of leptin on the production of TNF-alpha (tumor necrosis factor-alpha) by
      Kupffer cells (KCs) with signal transduction. Leptin enhanced TNF-alpha
      production accompanied by a dose-dependent increase of MAPK activity in
      lipopolysaccharide (LPS)-stimulated KCs. SB203580 and JNK inhibitor I, specific
      inhibitors of P38 and JNK, inhibited TNF-alpha production in KCs but PD98059, an
      inhibitor of the ERK pathway, did not affect TNF-alpha production by KCs.
      Recombinant constitutively active adenovirus (Ad)-MKK6 and-MKK7 increased TNF
      alpha production in KCs with activation of P38 and JNK without any change by Ad
      MEK1 delivery. On the other hand, KCs isolated from the Zucker rat (fa/fa), a
      leptin receptor-deficient rat, showed reduced production of TNF-alpha on
      stimulation with LPS. The delivery of Ad-MKK6 and-MKK7, but not Ad-MEK1,
      increased TNF-alpha production in KCs of Zucker rats with activation of P38 and
      JNK. Addition of leptin to normal rats increased LPS-induced hepatic TNF-alpha
      production in vivo and leptin receptor-deficient Zucker rats showed reduced
      hepatic TNF-alpha production on addition of LPS in vivo. These findings indicate
      that P38 and JNK pathways are involved in the signal transduction of leptin
      enhancement of LPS-induced TNF-alpha production.

PMID- 15979654
TI  - The effect of IL-1beta on the expression of matrix metalloproteinases and tissue
      inhibitors of matrix metalloproteinases in human chondrocytes.
AB  - Interleukin-1 (IL-1) plays key roles in altering cartilage matrix turnover. This
      turnover is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors
      of matrix metalloproteinases (TIMPs). In the present study, we examined the
      effect of IL-1beta on cell proliferation, alkaline phosphatase (ALPase) activity,
      and the expression of MMPs, and TIMPs in chondrocytes derived from normal human
      femoral cartilage. The cells were cultured in Dulbecco's modified Eagle's medium
      containing 15% fetal bovine serum and 0, 1, 10, or 100 U/ml of IL-1beta for up to
      28 days. The level of expression of MMPs and TIMPs was estimated by determining
      mRNA levels using real-time PCR and by determining protein levels using an enzyme
      linked immunosorbent assay. Cell proliferation decreased in the presence of IL
      1beta after day 21 of culture. ALPase activity decreased significantly in the
      presence of IL-1beta after day 10 of culture. The expression of MMP-1, -2, and -3
      increased markedly in the presence of IL-1beta after day 21 of culture. MMP-13
      expression increased markedly in the presence of IL-1beta on day 1 of culture,
      but decreased markedly after day 7. The expression of TIMP-1 increased
      significantly after day 14 of culture. The expression of TIMP-2 decreased
      significantly on day 1, but increased significantly from day 3 to day 14 of
      culture. These results suggest that IL-1beta may stimulate cartilage matrix
      turnover by increasing mainly MMP-13 production by the cells.

PMID- 15979655
TI  - Temporal dissociation of components of cognitive control dysfunction in severe
      TBI: ERPs and the cued-Stroop task.
AB  - Cognitive control comprises two essential interactive component processes: a
      regulative component supporting the activation and implementation of control and
      an evaluative component that monitors the need for regulative control and signals
      when adjustments in control are necessary. Survivors of severe traumatic brain
      injury (TBI) experience cognitive control impairments, but the specific nature of
      these impairments is poorly characterized. Using event-related potentials (ERPs)
      acquired in the context of a trial-by-trial task-switching version of the Stroop
      task we temporally dissociated the regulative and evaluative processes in order
      to shed light on the potential roles of these components in TBI-related cognitive
      control impairment. Behaviorally, TBI patients showed a specific performance
      deficit suggestive of a failure to implement cognitive control in the service of
      processing conflict information. ERP findings showed that TBI patients were
      impaired in both the implementation of control and subsequent detection and
      processing of conflict. TBI patients were also impaired on a measure of working
      memory capacity, a measure that correlated with the ability to implement
      regulative control and overcome conflict. These findings suggest that patients
      with predominantly chronic severe TBI patients are impaired on both regulative
      and evaluative components of cognitive control, and may have implications for the
      design and evaluation of behavioral and pharmacological remediation strategies.

PMID- 15979656
TI  - Time-specific ecological niche modeling predicts spatial dynamics of vector
      insects and human dengue cases.
AB  - Numerous human diseases-malaria, dengue, yellow fever and leishmaniasis, to name
      a few-are transmitted by insect vectors with brief life cycles and biting
      activity that varies in both space and time. Although the general geographic
      distributions of these epidemiologically important species are known, the
      spatiotemporal variation in their emergence and activity remains poorly
      understood. We used ecological niche modeling via a genetic algorithm to produce
      time-specific predictive models of monthly distributions of Aedes aegypti in
      Mexico in 1995. Significant predictions of monthly mosquito activity and
      distributions indicate that predicting spatiotemporal dynamics of disease vector
      species is feasible; significant coincidence with human cases of dengue indicate
      that these dynamics probably translate directly into transmission of dengue virus
      to humans. This approach provides new potential for optimizing use of resources
      for disease prevention and remediation via automated forecasting of disease
      transmission risk.

PMID- 15979657
TI  - Acceptability of azithromycin for the control of trachoma in Northern Tanzania.
AB  - Trachoma causes blindness; the prevention strategy includes mass antibiotic
      treatment. In a community in Northern Tanzania offered mass treatment with
      azithromycin for the control of trachoma, we used focus group discussions,
      individual interviews, questionnaires and direct observation to quantify, explore
      and contextualize reasons for acceptance or refusal of the drug. In the village
      studied, 76% of the population eligible to receive azithromycin were treated.
      Uptake was significantly higher among women (79% treated) than men (72%). Factors
      affecting acceptability included: local prevention norms (such as the belief that
      injections, rather than oral medicine, should be used for prevention);
      perceptions of drugs in general and azithromycin in particular; perceptions of
      the distribution team's expertise; witnessing adverse effects in others; and the
      timing, quality and quantity of information about azithromycin and its
      availability. Familiarity with trachoma as a blinding disease was significantly
      associated with uptake. Individuals who refused treatment seemed to be less
      altruistic than other respondents. Neither socio-economic status nor use of
      traditional healers was related to uptake. Pre-distribution community assessment
      and community education, advance notice of the distribution, standardized
      distribution guidelines and improved distributor training are recommended to
      maximize acceptance of azithromycin in future campaigns.

PMID- 15979658
TI  - Actin, myosin, cytokeratins and spectrin are components of the guinea pig sperm
      nuclear matrix.
AB  - The nuclear matrix (NM) of somatic cells is an internal nuclear framework
      structure, with a structural function and participation in DNA replication and
      transcription. The NM has been described in mouse, hamster and human spermatozoa.
      In this study, an NM structural component of the guinea pig sperm nucleus was
      obtained by removing nuclear proteins and DNA from DTT-CTAB nuclei. Removal was
      achieved with high ionic strength salt and microccocal nuclease treatments
      including a heparin treatment to cause a slight swelling of the nucleus and
      facilitate material extraction. Actin, myosin, cytokeratins and spectrin were
      detected associated to NM by indirect immunofluorescence, immunogold staining and
      Western blotting analysis using specific antibodies. The presence of NM in guinea
      pig sperm nucleus is shown for the first time and some of its components are
      identified. This is also the first report on cytokeratins and myosin presence in
      guinea pig sperm. A retarding effect of nuclear decondensation caused by heparin
      is induced after phalloidin and/or diacetyl-monoxime (a myosin ATPase activity
      inhibitor) treatment, suggesting a role for F-actin and myosin in the maintenance
      of nuclear stability in sperm. The actin role was supported by the decondensing
      effect that citochalasin D and gelsolin had on sperm nuclei.

PMID- 15979659
TI  - Predicting the risk of developmental toxicity from in vitro assays.
AB  - Reproductive toxicity refers to the adverse effects of a substance on any aspect
      of the reproductive cycle, including the impairment of reproductive function, the
      induction of adverse effects in the embryo, such as growth retardation,
      malformations, and death. Due to the complexity of the mammalian reproductive
      cycle, it is impossible to model the whole cycle in a single in vitro system in
      order to detect chemical effects on mammalian reproduction. However, the cycle
      can be broken down in its biological components which may be studied individually
      or in combination. This approach has the advantage that the target tissue/organ
      of a developmental toxicant can be identified. In specific areas of developmental
      toxicity, a number of useful and promising in vitro models are already available.
      The individual tests may be used as building blocks of a tiered testing strategy.
      So far, research has focused on developing and validating tests covering only a
      few components of the reproductive cycle, in particular organogenesis of the
      embryo, reflecting important concerns for teratogenic chemicals. During the last
      three decades, a number of established models and promising new developments have
      emerged that will be discussed, e.g. culture of mammalian embryos and embryonic
      cells and tissues and the use of embryonic stem cells.

PMID- 15979660
TI  - Distance learning and toxicology: new horizons for Paracelsus.
AB  - Distance learning offers many advantages to students and teachers of almost any
      scientific discipline. Toxicology is no exception. For example, should Paracelsus
      be interested in learning more about toxicology at Drexel University, he would
      have the opportunity to take two courses in this subject utilizing the content
      management software, WebCT. The two courses would offer a website from which he
      could view and/or download his notes for each class. He could correspond with the
      instructor as well as fellow students, participate in discussions about timely
      topics, and make presentations to the class, all via electronic communication.
      Moreover, his examinations would also be computerized. Although he might have the
      option of attending traditional "face-to-face" lectures with other students in
      the class, he could also access these lectures at any time from a remote location
      by using the archive of taped lectures on the class website. Overall, Paracelsus
      would have access to many tools to enhance his understanding of toxicology, and
      he probably would never have to worry about parking before class (!). The two
      WebCT modules in toxicology that we have developed at Drexel represent the
      successful migration of two courses from a traditional "face-to-face" model of
      classroom instruction to hybrid models that combine "face-to-face" interaction
      with online instruction. Student and faculty evaluations of these courses have
      been very positive. Future plans include linking the two modules together so that
      students in the advanced class can do "review" or "remedial" work in the basic
      module. Furthermore, a library of video clips is also planned in which
      researchers will be discussing their work on various toxicologic topics. Students
      will be able to access these clips as resources from which to write research
      papers.

PMID- 15979661
TI  - Recent advances using rodent models for predicting human allergenicity.
AB  - The potential allergenicity of newly introduced proteins in genetically
      engineered foods has become an important safety evaluation issue. However, to
      evaluate the potential allergenicity and the potency of new proteins in our food,
      there are still no widely accepted and reliable test systems. The best-known
      allergy assessment proposal for foods derived from genetically engineered plants
      was the careful stepwise process presented in the so-called ILSI/IFBC decision
      tree. A revision of this decision tree strategy was proposed by a FAO/WHO expert
      consultation. As prediction of the sensitizing potential of the novel introduced
      protein based on animal testing was considered to be very important, animal
      models were introduced as one of the new test items, despite the fact that non of
      the currently studied models has been widely accepted and validated yet. In this
      paper, recent results are summarized of promising models developed in rat and
      mouse.

PMID- 15979662
TI  - Role of transporters in placental transfer of drugs.
AB  - Human placenta functions as an important transport organ that mediates the
      exchange of nutrients and metabolites between maternal and fetal circulations.
      This function is made possible because of the expression of a multitude of
      transport proteins in the placental syncytiotrophoblast with differential
      localization in the maternal-facing brush border membrane versus the fetal-facing
      basal membrane. Even though the physiological role of most of these transport
      proteins is to handle nutrients, many of them interact with xenobiotics and
      pharmacological agents. These transport proteins therefore play a critical role
      in the disposition of drugs across the maternal-fetal interface, with some
      transporters facilitating the entry of drugs from maternal circulation into fetal
      circulation whereas others preventing such entry by actively eliminating drugs
      from the placenta back into maternal circulation. The net result as to whether
      the placenta enhances the exposure of the developing fetus to drugs and
      xenobiotics or functions as a barrier to protect the fetus from such agents
      depends on the types of transporters expressed in the brush border membrane and
      basal membrane of the syncytiotrophoblast and on the functional mode of these
      transporters (influx versus efflux).

PMID- 15979663
TI  - Safety assessment of novel foods and strategies to determine their safety in use.
AB  - Safety assessment of novel foods requires a different approach to that
      traditionally used for the assessment of food chemicals. A case-by-case approach
      is needed which must be adapted to take account of the characteristics of the
      individual novel food. A thorough appraisal is required of the origin,
      production, compositional analysis, nutritional characteristics, any previous
      human exposure and the anticipated use of the food. The information should be
      compared with a traditional counterpart of the food if this is available. In some
      cases, a conclusion about the safety of the food may be reached on the basis of
      this information alone, whereas in other cases, it will help to identify any
      nutritional or toxicological testing that may be required to further investigate
      the safety of the food. The importance of nutritional evaluation cannot be over
      emphasised. This is essential for the conduct of toxicological studies in order
      to avoid dietary imbalances, etc., that might lead to interpretation
      difficulties, but also in the context of its use as food and to assess the
      potential impact of the novel food on the human diet. The traditional approach
      used for chemicals, whereby an acceptable daily intake (ADI) is established with
      a large safety margin relative to the expected exposure, cannot be applied to
      foods. The assessment of safety in use should be based upon a thorough knowledge
      of the composition of the food, evidence from nutritional, toxicological and
      human studies, expected use of the food and its expected consumption. Safety
      equates to a reasonable certainty that no harm will result from intended uses
      under the anticipated conditions of consumption.

PMID- 15979664
TI  - Arsenic stimulates release of cytochrome c from isolated mitochondria via
      induction of mitochondrial permeability transition.
AB  - Arsenic trioxide, As(III), is a known environmental toxicant, co-carcinogen, and
      potent chemotherapeutic agent. In model experiments with isolated rat liver
      mitochondria, As(III) stimulated a dose-dependent, cyclosporin A-sensitive
      release of cytochrome c via induction of mitochondrial permeability transition
      and subsequent swelling of mitochondria. Mitochondrial GSH does not seem to be a
      target for As(III) which, however, appears to cause oxidative modification of
      thiol groups of pore forming proteins, notably adenine nucleotide translocase. In
      mouse embryonic fibroblasts, 10 microM As(III) stimulated cytochrome c release
      and apoptosis via a Bax/Bak-dependent mechanism. At high concentrations (125
      microM and higher), cells died by Bax/Bak-independent necrosis; at this
      concentration range As(III) targets mitochondria directly, particularly complex I
      of the mitochondrial respiratory chain. Since pyruvate, a substrate of complex I,
      is a predominant mitochondrial substrate in the cell, inhibition of complex I
      will cause mitochondrial instability and a decrease of Delta psi that facilitates
      permeability transition and necrotic cell death.

PMID- 15979665
TI  - Role of inflammation in cardiopulmonary health effects of PM.
AB  - The relationship between increased exposure to PM and adverse cardiovascular
      effects is well documented in epidemiological studies. Inflammation in the lungs,
      caused by deposited particles, can be seen as a key process that could mediate
      adverse effects on the cardiovascular system. There are at least three potential
      pathways that could lead from pulmonary inflammation to adverse cardiovascular
      effects. Firstly, inflammation in the lung could lead to systemic inflammation,
      which is well known to be linked to sudden death from cardiovascular causes.
      Systemic inflammation can lead to destabilization by activation of inflammatory
      processes in atheromatous plaques. Secondly, inflammation can cause an imbalance
      in coagulation factors that favor propagation of thrombi if thrombosis is
      initiated. Thirdly, inflammation could affect the autonomic nervous system
      activity in ways that could lead to alterations in the control of heart rhythm
      which could culminate in fatal dysrhythmia.

PMID- 15979666
TI  - Comparison of effects of estradiol (E2) with those of octylmethoxycinnamate (OMC)
      and 4-methylbenzylidene camphor (4MBC)--2 filters of UV light - on several
      uterine, vaginal and bone parameters.
AB  - OMC and 4MBC are 2 absorbers of ultraviolet light which are used in unknown
      quantities in sunscreens, cosmetics and plastic products to protect against UV
      light-induced damage of the skin or of fragrances or plastic material. From
      there, they were shown to reach surface water and/or by direct contamination or
      ingestion the human. Under various conditions in mice and rats, both substances
      were shown to be estrogenic. Therefore, we compared in vitro and in vivo the
      effects of chronic application of these compounds at 2 doses with those of E2,
      all administered via food. No signs of toxicity were observed under application
      of 0.6 mg E2, 57.5 or 275 mg of OMC, 57.5 or 250 mg of 4MBC; these amounts were
      ingested with 21 g of control food, 17.8 g E2 food, 20.6 g or 22.3 g OMC food and
      23.7 or 22.8 g 4MBC food. In the uterus, vagina and bone, E2 exerted the expected
      stimulatory effects which were minimally shared by OMC and 4MBC in the uterus and
      vagina as assessed by histology and determination of a variety of estrogen
      regulated genes such as insulin-like growth factor-1, progesterone receptor and
      estrogen receptor beta. In the bone, OMC had no effect, while 4MBC shared the
      antiosteoporotic effects of E2 as measured by quantitative computer tomography in
      the metaphysis of the tibia. The mechanism of action of 4MBC, however, appears to
      be different as E2 reduced serum osteocalcin and the C-terminal breakdown
      products of collagen-1alpha1 which were both increased by 4MBC. Taken together,
      these data indicate a very weak estrogenic effect of OMC and 4MBC in the uterus
      and in the vagina but not in the bone where 4MBC exerted antiosteoporotic effects
      by a different mechanism than E2.

PMID- 15979667
TI  - Gene-particulate matter-health interactions.
AB  - Inter-individual variation in human responses to air pollutants suggests that
      some subpopulations are at increased risk to the detrimental effects of pollutant
      exposure. Extrinsic factors such as previous exposure and nutritional status may
      influence individual susceptibility. Intrinsic (host) factors that determine
      susceptibility include age, gender, and pre-existing disease (e.g., asthma), and
      it is becoming clear that genetic background also contributes to individual
      susceptibility. Environmental exposures to particulates and genetic factors
      associated with disease risk likely interact in a complex fashion that varies
      from one population and one individual to another. The relationships between
      genetic background and disease risk and severity are often evaluated through
      traditional family-based linkage studies and positional cloning techniques.
      However, case-control studies based on association of disease or disease
      subphenotypes with candidate genes have advantages over family pedigree studies
      for complex disease phenotypes. This is based in part on continued development of
      quantitative analysis and the discovery and availability of simple sequence
      repeats and single nucleotide polymorphisms. Linkage analyses with genetically
      standardized animal models also provide a useful tool to identify genetic
      determinants of responses to environmental pollutants. These approaches have
      identified significant susceptibility quantitative trait loci on mouse
      chromosomes 1, 6, 11, and 17. Physical mapping and comparative mapping between
      human and mouse genomes will yield candidate susceptibility genes that may be
      tested by association studies in human subjects. Human studies and mouse modeling
      will provide important insight to understanding genetic factors that contribute
      to differential susceptibility to air pollutants.

PMID- 15979668
TI  - Insights into Parkinson's disease models and neurotoxicity using non-invasive
      imaging.
AB  - Loss of dopamine in the nigrostriatal system causes a severe impairment in motor
      function in patients with Parkinson's disease and in experimental neurotoxic
      models of the disease. We have used non-invasive imaging techniques such as
      positron emission tomography (PET) and functional magnetic resonance imaging
      (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic
      models of Parkinson's disease. In addition to classic neurotransmitter studies,
      in these models, it is also possible to characterize associated and perhaps
      pathogenic factors, such as the contribution of microglia activation and
      inflammatory responses to neuronal damage. Functional imaging techniques are
      instrumental to our understanding and modeling of disease mechanisms, which
      should in turn lead to development of new therapies for Parkinson's disease and
      other neurodegenerative disorders.

PMID- 15979669
TI  - Bystander effects, genomic instability, adaptive response, and cancer risk
      assessment for radiation and chemical exposures.
AB  - There is an increased interest in utilizing mechanistic data in support of the
      cancer risk assessment process for ionizing radiation and environmental chemical
      exposures. In this regard, the use of biologically based dose-response models is
      particularly advocated. The aim is to provide an enhanced basis for describing
      the nature of the dose-response curve for induced tumors at low levels of
      exposure. Cellular responses that might influence the nature of the dose-response
      curve at low exposures are understandably receiving attention. These responses
      (bystander effects, genomic instability, and adaptive responses) have been
      studied most extensively for radiation exposures. The former two could result in
      an enhancement of the tumor response at low doses and the latter could lead to a
      reduced response compared to that predicted by a linear extrapolation from high
      dose responses. Bystander responses, whereby cells other than those directly
      traversed by radiation tracks are damaged, can alter the concept of target cell
      population per unit dose. Similarly, induced genomic instability can alter the
      concept of total response to an exposure. There appears to be a role for
      oxidative damage and cellular signaling in the etiology of these cellular
      responses. The adaptive response appears to be inducible at very low doses of
      radiation or of some chemicals and reduces the cellular response to a larger
      challenge dose. It is currently unclear how these cellular toxic responses might
      be involved in tumor formation, if indeed they are. In addition, it is not known
      how widespread they are as regards inducing agents. Thus, their impact on low
      dose cancer risk remains to be established.

PMID- 15979670
TI  - Toxicovigilance: a new approach for the hazard identification and risk assessment
      of toxicants in human beings.
AB  - The concept of toxicovigilance encompasses the active detection, validation and
      follow-up of clinical adverse events related to toxic exposures in human beings.
      Poison centers are key players in this function as poisoning statistics are
      essential to define the cause, incidence and severity of poisonings occurring in
      the general population. In addition, the systematic search for unexpected shifts
      in the recorded causes of poisonings, e.g., following the introduction of a new
      product, or change in the formulation or recommended use of an old product,
      allows for a rapid detection of potential adverse health consequences and the
      implementation of preventive or corrective measures. However, toxicovigilance is
      genuinely a medical and not only a statistical approach of human toxicity issues.
      In contrast to epidemiology, toxicovigilance is based on the in-depth medical
      assessment of acute or chronic intoxications on an individual basis, which
      requires detailed information that poison centers can rarely obtain via emergency
      telephone calls and that epidemiologists cannot collect or process. Validation of
      this medical information must primarily be based on toxicological expertise to
      help identify causal links between otherwise unexplained pathological conditions
      and documented toxic exposures. Thus, toxicovigilance can contribute to hazard
      identification and risk assessment by providing medically validated data which
      are often overlooked in the process of risk assessment. So far, very few
      structured toxicovigilance systems have been set up and hopefully national and
      international initiatives will bridge this gap in our knowledge of the toxicity
      of many chemicals and commercial products in human beings.

PMID- 15979671
TI  - Non-precautionary aspects of toxicology.
AB  - Empirical studies in toxicology aim at deciphering complex causal relationships,
      especially in regard to human disease etiologies. Several scientific traditions
      limit the usefulness of documentation from current toxicological research, in
      regard to decision-making based on the precautionary principle. Among non
      precautionary aspects of toxicology are the focus on simplified model systems and
      the effects of single hazards, one by one. Thus, less attention is paid to
      sources of variability and uncertainty, including individual susceptibility,
      impacts of mixed and variable exposures, susceptible life-stages, and vulnerable
      communities. In emphasizing the need for confirmatory evidence, toxicology tends
      to penalize false positives more than false negatives. An important source of
      uncertainty is measurement error that results in misclassification, especially in
      regard to exposure assessment. Standard statistical analysis assumes that the
      exposure is measured without error, and imprecisions will usually result in an
      underestimation of the dose-effect relationship. In testing whether an effect
      could be considered a possible result of natural variability, a 5% limit for
      "statistical significance" is usually applied, even though it may rule out many
      findings of causal associations, simply because the study was too small (and thus
      lacked statistical power) or because some imprecision or limited sensitivity of
      the parameters precluded a more definitive observation. These limitations may be
      aggravated when toxicology is influenced by vested interests. Because current
      toxicology overlooks the important goal of achieving a better characterization of
      uncertainties and their implications, research approaches should be revised and
      strengthened to counteract the innate ideological biases, thereby supporting our
      confidence in using toxicology as a main source of documentation and in using the
      precautionary principle as a decision procedure in the public policy arena.

PMID- 15979672
TI  - Use of product databases for risk assessment purposes.
AB  - Product information databases are important prerequisites for providing data to
      poison centers (PC) to give adequate advice in cases of poisonings and for
      preparation of statistics as annual reports. For risk assessment measures, they
      can help for exposure assessments and for priority setting. A product database is
      a set of information of product and substance names, compositions, and uses of
      products. Data are provided due to national regulations as well as to national
      and international agreements between industry, international associations, e.g.
      the European Association of Poison Centres and Clinical Toxicologists (EAPCCT),
      and clinical toxicology institutions. They have different contents, i.e. complete
      formulations, frame formulations, and material safety data sheets. For definite
      identification of products, the product name should be readily taken from the
      labels and must be similar to the names provided by electronic media as
      databases. Products should be classified according to their use. The first system
      that has been prepared for that purpose is the ATC classification for
      pharmaceuticals. For chemicals, several systems e.g. the WHO-IPCS classification
      code, exist; the EU technical guidance document for risk assessment of chemicals
      is mentioning use categories, and they are used on national levels as well. For
      risk assessment purposes, statistics of poisonings and other health hazards are
      important as well as information about exposure. Linking cases of poisonings with
      product data enables risk assessors to perform statistical evaluations about
      health effects due to product use categories which can be compared to product
      compositions. If products are categorized by their use, information about use
      characteristics, such as frequencies and durations, can be derived. Hence,
      product categories can be taken to characterize scenarios and thus help for model
      estimations of exposure and respective doses.

PMID- 15979673
TI  - Augmented hepatic injury followed by impaired regeneration in metallothionein
      I/II knockout mice after treatment with thioacetamide.
AB  - A previous study (Oliver, J.R., Mara, T.W., Cherian, M.G. 2005. Impaired hepatic
      regeneration in metallothionein-I/II knockout mice after partial hepatectomy.
      Exp. Biol. Med. 230, 61-67) has shown an impairment of liver regeneration
      following partial hepatectomy (PH) in metallothionein (MT)-I and MT-II gene
      knockout (MT-null) mice, thus suggesting a requirement for MT in cellular growth.
      The present study was undertaken to investigate whether MT may play a similar
      role in hepatic injury and regeneration after acute treatment with thioacetamide
      (TAA). Hepatotoxicity of TAA is caused by the generation of oxidative stress. TAA
      was injected ip to both wild-type (WT) and MT-null mice. Mice were killed at 6,
      12, 24, 48, 60, and 72 h after injection of TAA (125 mg/kg) or 48 h after
      injection of saline (vehicle control), and different parameters of hepatic injury
      were measured. The levels of hepatic lipid peroxidation were increased at 12 h in
      both types of mice; however, lipid peroxidation was significantly less in WT mice
      than MT-null mice at 48 h after injection of TAA. Analysis of hepatic glutathione
      (GSH) levels after TAA injection showed depletion of GSH at 12 h in WT mice and
      at 6 h in MT-null mice; however, significantly more GSH was depleted early (6-24
      h) in MT-null mice than WT mice. An increase in hepatic iron (Fe) levels was
      observed in both types of mice after injection of TAA, but Fe levels were
      significantly higher in MT-null mice than WT mice at 6-60 h. The levels of
      hepatic copper (Cu) and zinc (Zn) were significantly higher in WT mice than MT
      null mice at 6-60 h for Cu, and at 24 h and 60 h for Zn, respectively.
      Histopathological examination showed hemorrhagic necrosis in the liver of both
      types of mice at 12-72 h, with hepatic injury being more prominent in MT-null
      mice than WT mice. The hepatic MT levels were increased in WT mice after
      injection of TAA, and were highest at 24-72 h. Immunohistochemical staining for
      MT in WT mice indicated the presence of MT in both nucleus and cytoplasm of
      hepatocytes at 24-72 h after TAA injection. Cell proliferation, as assessed by
      immunohistochemical staining for proliferating cell nuclear antigen, was detected
      mainly in the livers of WT mice at 48-72 h after TAA treatment. Hepatic
      proliferation index in MT-null mice was very low as compared to WT mice during
      liver regeneration after injection of TAA. These results show that the liver
      cells of MT-null mice with no functional MT are unable to regenerate after TAA
      induced hepatic injury, demonstrating an important role for MT in cellular
      regeneration.

PMID- 15979674
TI  - Polymorphic variations in the expression of the chemical detoxifying UDP
      glucuronosyltransferases.
AB  - The UDP glucuronosyltransferases (UGT) are expressed predominantly in the liver
      and gastrointestinal tract in humans. Their expression varies widely between
      individuals, due in part to coding region polymorphisms that alter catalytic
      function and in part, to differences in the regulation of UGT genes. The latter
      differences are most likely the result of polymorphisms in the regulatory
      elements of UGT genes and in the transcription factors that bind to these
      elements. Several frequent polymorphisms in the promoters of UGT genes have been
      described; however, few of these fall within critical regulatory elements and
      alter UGT expression. Some rare mutations alter UGT promoter activity in in vitro
      systems but their effect in the clinic is still to be confirmed. Several
      transcription factors that regulate UGT gene expression in cells of hepatic and
      intestinal origin have been identified. These include positive regulators of UGT
      gene expression such as hepatocyte nuclear factor 1 alpha (HNF1 alpha), octamer
      transcription factor-1 (Oct-1) and the intestine-specific transcription factor,
      caudal-related homeodomain protein 2 (Cdx2). Negative regulators include the Pre
      B cell homeobox factor (Pbx2) and its dimerization partner, Pbx regulating
      protein 1 (Prep1). Polymorphisms in these transcription factors may cause
      differences in their interaction and binding to UGT promoters. Current work
      describing the effects of these transcription factor polymorphisms on UGT
      expression will be described. Knowledge of UGT promoter elements and the proteins
      that bind to these elements, as well as knowledge of polymorphisms that alter
      their function, may aid in the prediction of an individual's response to
      chemicals and in the prediction of chemical toxicities.

PMID- 15979675
TI  - Ebselen: a thioredoxin reductase-dependent catalyst for alpha-tocopherol quinone
      reduction.
AB  - The thioredoxin system, composed of thioredoxin (Trx), thioredoxin reductase
      (TrxR), and NADPH, is a powerful protein disulfide reductase system with a broad
      substrate specificity. Recently the selenazol drug ebselen was shown to be a
      substrate for both mammalian TrxR and Trx. We examined if alpha-tocopherol
      quinone (TQ), a product of alpha-tocopherol oxidation, is reduced by ebselen in
      the presence of TrxR, since TQ was not a substrate for the enzyme itself. Ebselen
      reduction of TQ in the presence of TrxR was caused by ebselen selenol, generated
      from fast reduction of ebselen by the enzyme. TQ has no intrinsic antioxidant
      activity, while the product of reduction of TQ, alpha-tocopherolhydroquinone
      (TQH(2)), is a potent antioxidant. The thioredoxin system dependence of ebselen
      to catalyze reduction of other oxidized species, such as hydrogen peroxide,
      dehydroascorbate, and peroxynitrite, is discussed. The ability of ebselen to
      reduce TQ via the thioredoxin system is a novel mechanism to explain the effects
      of the drug as an antioxidant in vivo.

PMID- 15979677
TI  - Possibilities and pitfalls for modern biotechnology in the development of African
      genetic toxicology.
AB  - Developing countries are currently going through a transitional phase facing the
      new challenges of globalization and its potential negative impact. Research
      policy should highlight the need to mobilize resources for human resource
      development, networking, improved research culture, information sharing, and
      pragmatic use of research findings. Advancement in molecular genetics whether at
      the educational or research level should greatly progress in developing countries
      so as to improve diagnosis, treatment, understanding of disease risk factors, and
      prevention. Currently, there is a growing interest to genetic toxicology
      research, the use of different biomarkers, and genetic susceptibility testing,
      which can contribute effectively in risk assessment. Africa has unique
      environmental exposures and public health circumstances, which make it ideal for
      environmental mutagenicity and carcinogenicity research. There are exposures to
      chemical genotoxicants (e.g., automobile exhaust, pesticides, metals, and
      cytotoxic drugs) and to lifestyle factors (e.g., consumption of tobacco products)
      that have been linked to the expression of biological effects and to increased
      risk for cancer. Infections can be associated with cancer development when the
      environmental factors interact with the infection and lead to the enhancement of
      the carcinogenic process. The high prevalence of viral pathogens and the improper
      use of pesticides may endanger biological functions beyond those for which they
      originally manufactured. Biomarkers are used to detect the effects of pesticides
      before adverse clinical health occurs. The scientific community plays a crucial
      role in understanding the environmental causes of human health problems and
      through its collaboration with communities, industries, and government agencies
      can help in resolving health problems.

PMID- 15979676
TI  - The Tokyo subway sarin attack--lessons learned.
AB  - The sarin gas attack in the Tokyo subway system is reviewed from a clinical
      toxicology perspective. Based on the lessons learned from this attack, the
      following areas should be addressed on a global scale. First, an adequate supply
      of protective equipment is required, including level B protective equipment with
      a pressure demand breathing apparatus. In addition, a system should be
      established that enables a possible cause to be determined based on symptoms,
      physical findings, general laboratory tests, and a simple qualitative analysis
      for poisonous substances. If an antidote is needed, the system should enable it
      to be administered to the victims as quickly as possible. Preparation for a large
      scale chemical attack by terrorists requires the prior establishment of a
      detailed decontamination plan that utilizes not only mass decontamination
      facilities but also public facilities in the area. A system should be established
      for summarizing, evaluating, and disseminating information on poisonous
      substances. Finally, a large-scale scientific investigation of the Tokyo sarin
      attack should be conducted to examine its long-term and subclinical effects and
      the effects of exposure to asymptomatic low levels of sarin.

PMID- 15979678
TI  - Global gene mining and the pharmaceutical industry.
AB  - Worldwide efforts are ongoing in optimizing medical treatment by searching for
      the right medicine at the right dose for the individual. Metabolism is regulated
      by polymorphisms, which may be tested by relatively simple SNP analysis, however
      requiring DNA from the test individuals. Target genes for the efficiency of a
      given medicine or predisposition of a given disease are also subject to
      population studies, e.g., in Iceland, Estonia, Sweden, etc. For hypothesis
      testing and generation, several bio-banks with samples from patients and healthy
      persons within the pharmaceutical industry have been established during the past
      10 years. Thus, more than 100,000 samples are stored in the freezers of either
      the pharmaceutical companies or their contractual partners at universities and
      test institutions. Ethical issues related to data protection of the individuals
      providing samples to bio-banks are several: nature and extent of information
      prior to consent, coverage of the consent given by the study person, labeling and
      storage of the sample and data (coded or anonymized). In general, genetic test
      data, once obtained, are permanent and cannot be changed. The test data may imply
      information that is not beneficial to the patient and his/her family (e.g.,
      employment opportunities, insurance, etc.). Furthermore, there may be a long
      latency between the analysis of the genetic test and the clinical expression of
      the disease and wide differences in the disease patterns. Consequently,
      information about some genetic test data may stigmatize patients leading to poor
      quality of life. This has raised the issue of 'genetic exceptionalism' justifying
      specific regulation of use of genetic information. Discussions on how to handle
      sampling and data are ongoing within the industry and the regulatory sphere, the
      European Agency for the Evaluation of Medicinal Products (EMEA) having issued a
      position paper, the Council for International Organizations of Medical Sciences
      (CIOMS) having a working group on this issue, and the European Society of Human
      Genetics preparing background paper on 'Polymorphic sequence variants in
      medicine: Technical, social, legal and ethical issues. Pharmacogenetics as an
      example'. Within the European project Privacy in Research Ethics and Law
      (PRIVIREAL), recommendations for common European guidelines for membership in
      research ethical committees have been discussed, balancing the interests and
      assuring independence and legal competence. Good decision making, assuring
      legality of protocols and assessment of data protection is suggested to be part
      of any evaluation of protocols.

PMID- 15979680
TI  - The virion N protein of infectious bronchitis virus is more phosphorylated than
      the N protein from infected cell lysates.
AB  - Because phosphorylation of the infectious bronchitis virus (IBV) nucleocapsid
      protein (N) may regulate its multiple roles in viral replication, the dynamics of
      N phosphorylation were examined. 32P-orthophosphate labeling and Western blot
      analyses confirmed that N was the only viral protein that was phosphorylated.
      Pulse labeling with 32P-orthophosphate indicated that the IBV N protein was
      phosphorylated in the virion, as well as at all times during infection in either
      chicken embryo kidney cells or Vero cells. Pulse-chase analyses followed by
      immunoprecipitation of IBV N proteins using rabbit anti-IBV N polyclonal antibody
      demonstrated that the phosphate on the N protein was stable for at least 1 h.
      Simultaneous labeling with 32P-orthophosphate and 3H-leucine identified a 3.5
      fold increase in the 32P:3H counts per minute (cpm) ratio of N in the virion as
      compared to the 32P:3H cpm ratio of N in the cell lysates from chicken embryo
      kidney cells, whereas in Vero cells the 32P:3H cpm ratio of N from the virion was
      10.5-fold greater than the 32P:3H cpm ratio of N from the cell lysates. These
      studies are consistent with the phosphorylation of the IBV N playing a role in
      assembly or maturation of the viral particle.

PMID- 15979679
TI  - Early detection of dominant Env-specific and subdominant Gag-specific CD8+
      lymphocytes in equine infectious anemia virus-infected horses using major
      histocompatibility complex class I/peptide tetrameric complexes.
AB  - Cytotoxic T lymphocytes (CTL) are critical for control of lentiviruses, including
      equine infectious anemia virus (EIAV). Measurement of equine CTL responses has
      relied on chromium-release assays, which do not allow accurate quantitation.
      Recently, the equine MHC class I molecule 7-6, associated with the ELA-A1
      haplotype, was shown to present both the Gag-GW12 and Env-RW12 EIAV CTL epitopes.
      In this study, 7-6/Gag-GW12 and 7-6/Env-RW12 MHC class I/peptide tetrameric
      complexes were constructed and used to analyze Gag-GW12- and Env-RW12-specific
      CTL responses in two EIAV-infected horses (A2164 and A2171). Gag-GW12 and Env
      RW12 tetramer-positive CD8+ cells were identified in nonstimulated peripheral
      blood mononuclear cells as early as 14 days post-EIAV inoculation, and
      frequencies of tetramer-positive cells ranged from 0.4% to 6.7% of nonstimulated
      peripheral blood CD8+ cells during the 127-day study period. Although both horses
      terminated the initial viremic peak, only horse A2171 effectively controlled
      viral load. Neutralizing antibody was present during the initial control of viral
      load in both horses, but the ability to maintain control correlated with Gag-GW12
      specific CD8+ cells in A2171. Despite Env-RW12 dominance, Env-RW12 escape viral
      variants were identified in both horses and there was no correlation between Env
      RW12-specific CD8+ cells and control of viral load. Although Gag-GW12 CTL escape
      did not occur, a Gag-GW12 epitope variant arose in A2164 that was recognized less
      efficiently than the original epitope. These data indicate that tetramers are
      useful for identification and quantitation of CTL responses in horses, and
      suggest that the observed control of EIAV replication and clinical disease was
      associated with sustained CTL recognition of Gag-specific epitopes.

PMID- 15979681
TI  - Spatial and temporal aspects of oculomotor inhibition as revealed by saccade
      trajectories.
AB  - The spatial and temporal effect of distractor related inhibition on stimulus
      elicited (reflexive) and goal driven (voluntary) saccades, was examined using
      saccade trajectory deviations as a measure. Subjects made voluntary and reflexive
      saccades to a target location on the vertical midline, while the distance of a
      distractor from the target was systematically manipulated. The trajectory
      curvature of both voluntary and reflexive saccades was found to be subject to
      individual differences. Saccade curvature was found to decrease monotonically
      with increasing distractor distance from target for some subjects while for
      others no reduction in curvature or even an increase was found. These results
      could not be explained by latency differences or landing position effects. The
      different patterns of distractor effects on saccade trajectories suggest the
      additional influence of a non-spatial inhibitory mechanism.

PMID- 15979682
TI  - Precipitation of enzyme-catalyzed phenol oxidative coupling products: background
      ion and pH effects.
AB  - The effects of solution pH and background ion types and concentrations on the
      precipitation of polymeric products generated in the catalytically facilitated
      oxidative coupling of phenol were investigated systematically. The coupling
      reactions mediated by horseradish peroxidase were carried out under a specific
      predetermined experimental condition. Acids, bases, and/or selected salts of ions
      having different valences were then added to the resulting product solutions to
      adjust pH and ionic conditions. Subsequent analyses of product distributions
      between dissolved and precipitated forms revealed that ionic conditions and pH
      significantly impact those distributions, and associated mechanisms are
      discussed. The findings reported will assist feasibility assessments and process
      optimization with respect to engineering applications of catalyzed oxidative
      coupling reactions for wastewater treatment and soil decontamination.

PMID- 15979683
TI  - Chemical coupling of photocatalysis with flocculation and adsorption in the
      removal of organic matter.
AB  - An experimental investigation was made to study the effects of chemical coupling
      of flocculation and adsorption with photocatalysis in treating persistent organic
      pollutants in wastewater. The photocatalysis alone showed initial reverse
      reaction when titanium oxide (TiO(2)) was used in catalysis. The effect of the
      pretreatment of adsorption with powdered activated carbon (PAC) on photocatalysis
      was studied. The results showed that PAC adsorption followed by photocatalysis
      was not effective in alleviating reverse reaction. On the other hand, when PAC
      and TiO(2) were added simultaneously, the reverse reaction was eliminated.
      Further, the organic removal was also improved by simultaneous PAC and TiO(2)
      additions. When flocculation with ferric chloride (FeCl(3)) was used as
      pretreatment, the organic removal efficiency was superior. The initial reverse
      reaction was also eliminated/minimized. However, inadequate doses of FeCl(3)
      (less than 30 mgl(-1)) resulted in initial reverse reaction and inferior DOC
      removal.

PMID- 15979684
TI  - The effects of phosphorus additions on the sedimentation of contaminants in a
      uranium mine pit-lake.
AB  - We investigated the usefulness of phytoplankton for the removal of surface water
      contaminants. Nine large mesocosms (92.2m(3)) were suspended in the flooded DJX
      uranium pit at Cluff Lake (Saskatchewan, Canada), and filled with highly
      contaminated mine water. Each mesocosm was fertilized with a different amount of
      phosphorus throughout the 35 day experiment to stimulate phytoplankton growth,
      and to create a range in phosphorus load (g) to examine how contaminants may be
      affected by different nutrient regimes. Algal growth was rapid in fertilized
      mesocosms (as demonstrated by chlorophyll a profiles). As phosphorus loads
      increased there were significant declines (p<0.05) in the surface water
      concentrations of As, Co, Cu, Mn, Ni, and Zn. This decline was near significant
      for uranium (p=0.065). The surface water concentrations of Ra-226, Mo, and Se
      showed no relationship to phosphorus load. Contaminant concentrations in sediment
      traps suspended at the bottom of each mesocosm generally showed the opposite
      trend to that observed in the surface water, with most contaminants (As, Co, Cu,
      Mn, Ni, Ra-226, U, and Zn) exhibiting a significant positive relationship
      (p<0.05) with phosphorus load. Selenium and Mo did not respond to nutrient
      treatments. Our results suggest that phytoremediation has the potential to lower
      many surface water contaminants through the sedimentation of phytoplankton. Based
      on our results, we estimate that the Saskatchewan Surface Water Quality
      Objectives (SSWQO) for DJX pit would be met in approximately 45 weeks for Co, 65
      weeks for Ni, 15 weeks for U, and 5 weeks for Zn.

PMID- 15979685
TI  - Transport and deposition of sediment-associated Escherichia coli in natural
      streams.
AB  - The association of microorganisms with sediment particles is one of the primary
      complicating factors in assessing microbial fate in aquatic systems. The
      literature indicates that the majority of enteric bacteria in aquatic systems are
      associated with sediments and that these associations influence their survival
      and transport characteristics. Yet, the nature of these associations has not been
      fully characterized. In this study, a combination of field experiments and
      mathematical modeling were used to better understand the processes which control
      the fate and transport of enteric bacteria in alluvial streams. An experimental
      procedure, involving the use of a tracer-bacteria, was developed to simulate the
      transport and deposition of bacteria-laden bed sediments in a small alluvial
      stream during steady flow conditions. The experimental data and mathematical
      model were used to determine dispersion coefficients, deposition rates, and
      partitioning coefficients for sediment-associated bacteria in two natural
      streams. The results provided evidence that bacterial adsorption can be modeled
      as an irreversible process in freshwater environments. Net settling velocities of
      fine sediments and associated bacteria were typically two orders of magnitude
      lower than those predicted from Stokes equation, due to re-entrainment of settled
      particles. The information presented in this study will further the development
      of representative microbial water quality models.

PMID- 15979686
TI  - Arsenate removal from water using sand--red mud columns.
AB  - This study describes experiments in which sorption filters, filled with
      chemically modified red mud (Bauxsol) or activated Bauxsol (AB) coated sand, are
      used to remove As(V) (arsenate) from water. Bauxsol-coated sand (BCS) and AB
      coated sand (ABCS) are prepared by mixing Bauxsol or AB with wet sand and drying.
      Samples of the BCS and ABCS are also used in batch experiments to obtain isotherm
      data. The observed adsorption data fit the Langmuir model well, with adsorption
      maxima of 3.32 and 1.64 mgg(-1) at pH values of 4.5 and 7.1, respectively for
      BCS; and of 2.14 mgg(-1) for ABCS at a pH of 7.1. Test results show that higher
      arsenate adsorption capacities can be achieved for both BCS and ABCS when using
      the columns compared to results for batch experiments; the difference is greater
      for BCS. Additional batch tests, carried out for 21 days using BCS to explain the
      observed discrepancy, show that the equilibrium time previously used in batch
      experiments was too short because adsorption continued for at least 21 days and
      reached 87% after 21 days compared to only 35% obtained after 4h. Fixed bed
      column tests, used to investigate the effects of flow rate and initial arsenate
      concentration indicate that the process is sensitive to both parameters, with
      lower flow rates (longer effective residence times in the columns) and initial
      arsenate concentrations providing better column performance. An examination of
      the combined effect of potential competing anions (i.e. silicate, phosphate,
      sulphate and bicarbonate) on the column performance showed that the presence of
      these anions in tap water slightly decreases arsenate removal. Each breakthrough
      curve is compared to the Thomas model, and it is found that the model may be
      applied to estimate the arsenate sorption capacity in columns filled with BCS and
      ABCS. The data obtained from both batch and column studies indicate that BCS and
      ABCS filtration could be effectively used to remove arsenate from water, with the
      latter being more efficient.

PMID- 15979688
TI  - The influence of organic ligands on the retention of lead in soil.
AB  - Organic acids are commonly produced and exuded by plant roots and soil
      microorganisms. Some of these organic compounds are effective chelating agents
      and have the potential to enhance metal mobility. The effect of citrate and
      salicylate on the leaching of lead in soil was investigated in a laboratory
      experiment. In short-term batch experiments, adsorption of lead to soil was
      slightly enhanced with increasing salicylate concentration (500-5000 microM) but
      decreased significantly in the presence of citrate. These observations suggested
      that citrate may enhance Pb leaching, but this was not observed in the column
      study. Soluble Pb in the presence and absence citrate or salicylate (up to 5000
      microM) was added to soil columns at a moderate flow rate, but no Pb was observed
      to emerge from the soil in any of the soil columns. Rapid biodegradation of
      citrate in soil eliminated potential complexing ability. Breakthrough of Pb from
      soil was noted only when using small columns at high flow rates (>20 pore volumes
      per day). Under these conditions of physical and chemical non-equilibrium,
      citrate was not degraded and significantly enhanced Pb mobility. As in the batch
      adsorption experiments, the presence of salicylate reduced Pb leaching.
      Considering the extreme conditions required to induce Pb leaching, it is likely
      that Pb will remain relatively immobile in soil even in the presence of a strong
      complexing agent such as citrate.

PMID- 15979687
TI  - Analysis of 4-nonylphenols, phthalates, and polychlorinated biphenyls in soils
      and biosolids.
AB  - When sewage sludge is added to agricultural land, organic chemicals contaminants
      are also added. The fate of these chemicals, particularly those shown to have
      oestrogenic potential, has received much research and regulatory interest in
      recent years. A method was developed for the analysis of 4-nonylphenols,
      phthalates, and PCB congeners in soils, mesophilic anaerobially digested
      dewatered (MADD) sewage sludge, and MADD sludge-amended soil. After Soxhlet
      extraction, the 4-nonylphenols and phthalates were separated from the PCBs on an
      isolute cyanopropyl SPE cartridge and analysed by GC-MS directly. The PCBs were
      acid treated on a Bakerbond PCB-A cartridge, then passed through a gel filtration
      column of Biobeads SX-3 resin, before GC-MS analysis. The method was successfully
      validated and then used for routine analysis, where average recoveries of the
      surrogate standards were 83+/-17% (4-n-heptylphenol), 96+/-11% (dimethyl-tere
      phthalate), 101+/-12% (dibenzyl-phthalate), and 79+/-13% (PCBs 6, 54, 104, 155,
      and 198).

PMID- 15979689
TI  - Influences of salinity on the biokinetics of Cd, Se, and Zn in the intertidal
      mudskipper Periophthalmus cantonensis.
AB  - The biokinetics (aqueous uptake, dietary assimilation, and elimination) of Cd,
      Se, and Zn in the intertidal mudskipper, Periophthalmus cantonensis, were
      examined at different acclimated salinities using the radiotracer technique. The
      dietary assimilation efficiency from ingested radiolabeled polychaetes was the
      highest for Se (32-40%), followed by Zn (5-7%) and Cd (2-3%), and was not
      influenced by salinity within a range of 10-30 psu. Uptake from the dissolved
      phase typically exhibited a linear pattern within the first 12 h of exposure,
      followed by a second slower uptake. The highest concentration factor (CF) was
      found for Zn, followed by Cd and Se. Differences in salinity did not
      significantly affect the CF of the three metals within the first 12 h, but the
      CFs were significantly higher at lower salinities (10-20 psu) than at the highest
      salinity (30 psu) by the end of 48 h exposure. Because the degrees to which the
      uptake of Se (a metalloid) and Cd/Zn were affected by salinity were comparable,
      we concluded that metal speciation as a result of salinity change was not
      important in leading to a change in metal CF. Physiological changes may be
      responsible for the increasing uptake at lowered salinity. The elimination rates
      of the three metals (0.01-0.06 d(-1)) were not significantly affected by
      salinity, but Se was eliminated at a faster rate following aqueous uptake than
      following dietary ingestion. There was no consistent influence of exposure routes
      on Cd and Zn elimination. The accumulated Cd was mainly associated with the gut,
      whereas the muscle was the dominant target site for Se and Zn accumulation.

PMID- 15979690
TI  - Effects of co-exposure to extremely low frequency (50 Hz) magnetic fields and
      xenobiotics determined in vitro by the alkaline comet assay.
AB  - In the present study, we used human peripheral blood leukocytes from 4 different
      donors, to investigate in vitro the possible genotoxic and/or co-genotoxic
      activity of extremely low frequency magnetic fields (ELF-MF) at 3 mT intensity.
      Two model mutagens were used to study the possible interaction between ELF-MF and
      xenobiotics: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline N
      oxide (4NQO). Primary DNA damage was evaluated by the alkaline single-cell
      microgel-electrophoresis ("comet") assay. Control cells (leukocytes not exposed
      to ELF-MF, nor treated with genotoxins) from the different blood donors showed a
      comparable level of basal DNA damage, whereas the contribution of individual
      susceptibility toward ELF-MF and the tested genotoxic compounds led to
      differences in the extent of DNA damage observed following exposure to the
      genotoxins, both in the presence and in the absence of an applied ELF-MF. A 3 mT
      ELF-MF alone was unable to cause direct primary DNA damage. In leukocytes exposed
      to ELF-MF and genotoxins, the extent of MNNG-induced DNA damage increased with
      exposure duration compared to sham-exposed cells. The opposite was observed in
      cells treated with 4NQO. In this case the extent of 4NQO-induced DNA damage was
      somewhat reduced in leukocytes exposed to ELF-MF compared to sham-exposed cells.
      Moreover, in cells exposed to ELF-MF an increased concentration of GSH was always
      observed, compared to sham-exposed cells. Since following GSH conjugation the
      genotoxic pattern of MNNG and 4NQO is quite different, an influence of ELF-MF on
      the activity of the enzyme involved in the synthesis of GSH leading to different
      activation/deactivation of the model mutagens used was hypothesized to explain
      the different trends observed in MNNG and 4NQO genotoxic activity in the presence
      of an applied ELF-MF. The possibility that ELF-MF might interfere with the
      genotoxic activity of xenobiotics has important implications, since human
      populations are likely to be exposed to a variety of genotoxic agents
      concomitantly with exposure to this type of physical agent.

PMID- 15979691
TI  - Risk assessment of combined photogenotoxic effects of sunlight and food
      additives.
AB  - The presence of flavored colorants (peach and raspberry), flavors (caramel,
      citric acid and vanilla) and food preservatives (sodium nitrite, sodium nitrate,
      sodium benzoate, benzoic acid, potassium sorbate and sodium chloride) in
      Escherichia coli suspension during exposure to sunlight did not change the extent
      of cell survival. No effect on viability and mutation induction (kanamycin
      resistant) was also seen when cells were kept in contact with any of the
      additives for 80 min in the dark. However, when the relevant additive was present
      in cell suspension during sunlight exposure the number of induced mutations was
      increased to varying extents over that seen with sunlight alone. Raspberry and
      peach increased the number of mutations in a dose dependent manner, while vanilla
      produced mutations in an additive fashion. Nitrite, nitrate, benzoate, sorbate
      and benzoic acid increased mutation somewhat additively over that of sunlight.
      Sodium chloride and citric acid were not effective. The impact of this
      investigation reflects the significance of combination of sunlight and chemical
      food additives as potential risk, which requires special attention and
      necessitates further investigations to evaluate the risk.

PMID- 15979692
TI  - Solid state partitioning of trace metals in suspended particulate matter from a
      river system affected by smelting-waste drainage.
AB  - The partitioning of particulate trace metals was investigated during one year of
      monthly sampling of suspended particulate matter (SPM) at eight sites along the
      Lot-Garonne fluvial system, known for its polymetallic pollution. The chemical
      partitioning in five operationally defined fractions (exchangeable/carbonate,
      Fe/Mn oxides, organic matter/sulfides, acid soluble, residual) was determined
      using a multiple single extraction approach. This approach showed that Cd, Zn, Pb
      and Cu were mainly associated with acid soluble phases (84-95%, 65-88%, 61-82%
      and 55-80% of the respective total metal content), and therefore showed a high
      mean potential of mobilization and bioavailability. In the Riou-Mort River,
      draining the smelting-wastes, Zn, Cd and Mn showed high mobility as they were
      little associated with the residual fraction (1-2%) and mainly bound to the
      'exchangeable' fraction of SPM (60-80%), probably weakly adsorbed on amorphous
      freshly-precipitated sulfide and/or oxide phases. Upstream and downstream of the
      anthropogenic source of metallic pollution, Mn and Cd, and Zn to a lesser extent,
      remained highly reactive. The other trace metals were mainly associated with the
      residual fraction and thus less mobile. However, the multiple single extraction
      scheme revealed that the most reactive transport phases were non-selectively
      extracted by the conventional extractants used here. These selectivity problems
      could not have been observed if sequential extraction was used.

PMID- 15979693
TI  - Recent advances in understanding sex differences in cardiac repolarization.
AB  - A number of gender differences exist in the human electrocardiogram (ECG): the P
      wave and P-R intervals are slightly longer in men than in women, whilst women
      have higher resting heart rates than do men, but a longer rate-corrected QT
      (QT(C)) interval. Women with the LQT1 and LQT2 variants of congenital long-QT
      syndrome (LQTS) are at greater risk of adverse cardiac events. Similarly, many
      drugs associated with acquired LQTS have a greater risk of inducing torsades de
      pointes (TdP) arrhythmia in women than in men. There are also male:female
      differences in Brugada syndrome, early repolarisation syndrome and sudden cardiac
      death. The differences in the ECG between men and women, and in particular those
      relating to the QT interval, have been explored experimentally and provide
      evidence of differences in the processes underlying ventricular repolarization.
      The data available from rabbit, canine, rat, mouse and guinea pig models are
      reviewed and highlight involvement of male:female differences in Ca and K
      currents, although the possible involvement of rapid and persistent Na current
      and Na-Ca exchange currents cannot yet be excluded. The mechanisms underlying
      observed differences remain to be elucidated fully, but are likely to involve the
      influence of gonadal steroids. With respect to the QT interval and risk of TdP, a
      range of evidence implicates a protective role of testosterone in male hearts,
      possibly by both genomic and non-genomic pathways. Evidence regarding oestrogen
      and progesterone is less unequivocal, although the interplay between these two
      hormones may influence both repolarization and pro-arrhythmic risk.

PMID- 15979694
TI  - The Noble cardiac ventricular electrophysiology models in CellML.
AB  - We present a review of the cardiac ventricular cell electrophysiology models
      developed by Prof. Denis Noble and colleagues as an example of how models may be
      published using a web-based CellML publication framework. The models reviewed
      have been marked-up in CellML and then used to compute all results presented
      here. The models are freely available from a website as are the specific
      numerical experiments discussed in this review and the tools used to perform the
      simulations.

PMID- 15979696
TI  - Society of Gynecologic Oncologists Clinical Practice Committee Statement on
      Prophylactic Salpingo-oophorectomy.

PMID- 15979695
TI  - Intraoperative electrical stimulation of the pelvic splanchnic nerves during
      nerve-sparing radical hysterectomy.
AB  - OBJECTIVES: This study sought to determine whether intraoperative electrical
      stimulation (IES) of pelvic splanchnic nerves (PSNs) while monitoring bladder
      contraction was useful to predict postoperative bladder function during
      conventional nerve-sparing radical hysterectomy. METHODS: Seventeen patients with
      stage Ib or IIa cervical cancer underwent conventional radical hysterectomy. IES
      was performed in all cases, stimulating the roots of PSN, the posterior sheath of
      the vesicouterine ligament (PVL) and the dorsal area of the ligament. After
      resection of the uterus, the PSN roots were stimulated again. Bladder function
      was evaluated by urodynamic study (UDS) preoperatively and 3 months after
      surgery. RESULTS: The results of IES were consistent with bladder function
      evaluated by postoperative UDS. In 13 of 17 cases, an increased intravesical
      pressure was observed with IES of the PSN roots after uterus resection. Nine of
      13 cases showed marked detrusor contraction with UDS 3 months after surgery and
      were able to void without using abdominal pressure except in one case. In the
      remaining 4 of 17 cases, no response could be detected to IES on either side.
      Three cases voided using abdominal pressure and one used clean intermittent self
      catheterization without spontaneous voiding. CONCLUSIONS: IES while monitoring
      intravesical pressure during radical hysterectomy represents a technically simple
      and useful procedure for the prediction of postoperative bladder function.

PMID- 15979697
TI  - Body weight and body mass index and ovarian cancer risk: a case-control study in
      China.
AB  - OBJECTIVE: To investigate the association between ovarian cancer risk and body
      height, weight, and BMI. METHODS: A hospital-based case-control study was
      conducted in China from 1999 to 2000. The study sample included 254 cases with
      histologically confirmed epithelial ovarian cancer and 652 controls. Information
      of adult height and weight at diagnosis, at 5 years before diagnosis and at age
      21 years, was collected by face-to-face interview using a structured
      questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained
      using unconditional logistic regression analyses. RESULTS: The ovarian cancer
      risk was significantly increased with higher body weight and BMI at 5 years
      before diagnosis, but not at diagnosis nor at age 21 years. The adjusted ORs were
      1.67 (95% CI = 1.04-2.67) for body weight >60 kg versus < or =50 kg and 1.75 (95%
      CI = 1.13-2.72) for BMI > or = 25.0 versus 18.5-21.9 at 5 years before diagnosis.
      There was no association between body height and ovarian cancer risk. CONCLUSION:
      Pre-morbid body weight and BMI were associated with an increased risk of ovarian
      cancer in Chinese women.

PMID- 15979698
TI  - Embolization for hemorrhage of liver metastases from choriocarcinoma.
AB  - BACKGROUND: Because gestational trophoblastic disease (GTD) is highly sensitive
      to chemotherapy, life-threatening hemorrhage from metastases can occur especially
      early after starting therapy. CASES: Two cases of post-term choriocarcinoma with
      liver metastases complicated by profuse life-threatening hemorrhage are reported.
      Emergency treatment with transcatheter angiographic embolization of the hepatic
      artery was performed to control bleeding. DISCUSSION: Although embolization of
      the iliac vessels for gynecologic malignancies, including GTD, have been
      described, this is the first time that embolization of the hepatic artery to
      control bleeding from liver metastases in GTD is reported. The use and
      indications for embolization are expanding, and also in acute hemorrhagic
      complications in GTD, this intervention should be considered.

PMID- 15979699
TI  - Enrichment of in vitro maturation medium for buffalo (Bubalus bubalis) oocytes
      with thiol compounds: effects of cystine on glutathione synthesis and embryo
      development.
AB  - The purpose of this study was to evaluate whether enriching the oocyte in vitro
      maturation medium with cystine, in the presence of cysteamine, would improve the
      in vitro embryo production efficiency in buffalo by further increasing the GSH
      reservoir created by the oocyte during maturation. Cumulus-oocytes complexes were
      matured in vitro in TCM 199 + 10% FCS, 0.5 microg/ml FSH, 5 microg/ml LH and 1
      microg/ml 17beta-estradiol in the absence or presence of cysteamine (50 microM),
      with or without 0.3mM cystine. In Experiment 1, glutathione content was measured
      by high-performance liquid chromatography and fluorimetric analysis in
      representative samples of oocytes matured in the four different experimental
      conditions. In Experiment 2, oocytes were fixed and stained to assess nuclear
      maturation and normal pronuclear development following IVM and IVF respectively.
      In Experiment 3, mature oocytes were in vitro fertilized and cultured to assess
      development to blastocysts. In all supplemented groups the intracytoplasmic GSH
      concentration was significantly higher than the control, with the highest GSH
      levels in oocytes matured in the presence of both thiol compounds (3.6, 4.7, 5.4
      and 6.9 picomol/oocyte in the control, cysteamine, cystine and cystine+cysteamine
      groups, respectively; P < 0.05). Cystine supplementation of IVM medium, both in
      the presence or absence of cysteamine, significantly increased the proportion of
      oocytes showing two normal synchronous pronuclei following fertilization. In all
      supplemented groups, cleavage rate was significantly improved compared to the
      control (55, 66.1, 73.5 and 78.4% in the control, cysteamine, cystine and
      cystine+cysteamine groups, respectively; P < 0.05). Similarly, blastocyst yield
      was also increased in the three enriched groups compared to the control (17.1,
      23.8, 29.3, 30.9% in the control, cysteamine, cystine and cystine+cysteamine
      groups, respectively; P < 0.05). Overall, the addition of cystine to a cysteamine
      enriched medium resulted in a significant increase of cleavage rate and
      transferable embryo yield compared to the medium supplemented with only
      cysteamine.

PMID- 15979700
TI  - Nanoconstructions based on double-stranded nucleic acids.
AB  - We describe the formation and properties of nanoconstruction that consists of the
      double-stranded DNA molecules located at distance of 35-50 A in the spatial
      structure of particles of their cholesteric liquid-crystalline dispersions and
      cross-linked by artificial nanobridges. The resulting nanostructures possess the
      peculiar spatial and optical properties.

PMID- 15979701
TI  - Direct patterning of mammalian cells onto porous tissue engineering substrates
      using agarose stamps.
AB  - This paper describes simple, inexpensive, and potentially generic methodology for
      generating patterns of mammalian cells on porous scaffolds for tissue engineering
      using replica printing. Circular patterns (diameter: 200, 700, and 1000 microm)
      of human osteoblasts were transferred directly from topographically patterned
      agarose stamps onto porous hydroxyapatite scaffolds or onto fibronectin-coated
      glass slides. The use of hydrogel stamps provided a "wet", biocompatible surface
      and maintained the viability of cells adsorbed on stamps during the patterning
      process. Stamps inked once with suspensions of cells allowed the repeated
      patterning of substrates. Direct stamping of human osteoblasts (and, potentially
      other mammalian cells) can be used to control the size, spacing, and geometry of
      patterns of cells printed on porous tissue engineering substrates. This approach
      may find use in controlling the spatial invasion of scaffolds, promoting the
      hierarchical organization of cells, and in controlling cell-cell interactions as
      a step in preservation of phenotypes of cells.

PMID- 15979702
TI  - The effect of steroid on myeloid leukemic cells: the potential of short-course
      high-dose methylprednisolone treatment in inducing differentiation, apoptosis and
      in stimulating myelopoiesis.
AB  - Several in vitro studies have shown that dexamethasone (Dex) and prednisolone can
      induce differentiation of some mouse and human myeloid leukemic cells to
      macrophages and granulocytes. Based on in vitro experiments, we have shown that
      short-course (3-7 days) high-dose methylprednisolone (HDMP) (20-30 mg/kg/day)
      treatment can induce differentiation of myeloid leukemic cells in vivo in
      children with different subtypes of acute myeloblastic leukemia (AML) (AML-M1, 
      M2, -M3, -M4, -M7). We have also shown that induction of apoptosis of myeloid
      leukemic cells with or without differentiation is possible by short-course HDMP
      treatment. In addition, short-course HDMP treatment has been shown to be
      effective in accelerating leukocyte recovery, possibly stimulating normal CD34
      positive hematopoietic progenitor cells. Addition of HDMP to mild cytotoxic
      chemotherapy (low-dose cytosine arabinoside (LD-Ara-c), weekly mitoxantrone and
      Ara-c or 6-thioguanine) increased the remission rate (87-89%) and improved the
      outcome of AML children. We believe that the results of our 17-year clinical
      experience will provide important benefits to AML patients.

PMID- 15979703
TI  - Functional T-cell anergy in a case of persistent polyclonal B-cell lymphocytosis.
AB  - The T-cell population of a patient with persistent polyclonal B-cell
      lymphocytosis (PPBL) presenting with an intermittent Epstein-Barr virus (EBV)
      associated disease was studied. Unstimulated T-cells did not express CD40 ligand
      (CD40L), whereas activation with IL-2 led to expression of this costimulatory
      molecule. CD40L expression was inhibited upon incubation with the supernatant of
      an EBV-positive B-cell line (SM) which had been grown spontaneously from the
      patient's peripheral blood cells. The supernatant of SM cells effectively
      inhibited cytotoxic T-cells. Elevated levels of IL-10, TNF-alpha and soluble CD40
      were found in the supernatant of SM cells. Additionally, enhanced levels of LMP-1
      protein were detected.

PMID- 15979704
TI  - Complete response in a patient with adult T-cell leukemia (ATL) treated with
      combination of alemtuzumab and pentostatin.
AB  - Treatment of adult T-cell leukemia (ATL) remains difficult. Alemtuzumab with or
      without nucleoside analogs such as pentostatin may provide a role in this
      setting. However, the associated immunosuppression is a concern in patients with
      viral-mediated disease.

PMID- 15979705
TI  - Foster home care is more cost-effective than shelter care: serious questions
      continue to be raised about the utility of group care in child welfare services.

PMID- 15979706
TI  - SAFE Homes: is it worth the cost? An evaluation of a group home permanency
      planning program for children who first enter out-of-home care.
AB  - OBJECTIVE: To evaluate the SAFE Homes (SH) program, a short-term group care
      program for children between 3 and 12 years of age who enter care for the first
      time. The program aims to improve case outcomes by consolidating resources to
      facilitate assessment and treatment planning. METHODS: The 1-year outcomes of 342
      children who received SAFE Home services and 342 matched foster care (FC) control
      children were compared. The 684 subjects used in this report were selected from a
      larger pool of 909 subjects using propensity score matching to control for hidden
      bias in treatment group assignment. We hypothesized that SAFE Homes would result
      in greater continuity of care for children (e.g., fewer placements, more
      placements with siblings and in towns of origin), identification of more
      relatives for substitute care when needed, reduced use of high-cost restrictive
      care settings (e.g., residential, inpatient), and reduced rates of re-abuse
      through earlier detection and provision of services to meet child and family
      treatment needs. RESULTS: Prior to the initiation of the SAFE Homes program, 75%
      of the children who entered care in the State experienced three or more
      placements in the first year. The outcomes of both the SH and FC cases were
      significantly improved over pre-SAFE Home State statistics. The FC group,
      however, had comparable or better outcomes on most variables examined. In
      addition, the total cost for out-of-home care for the children in FC was
      significantly less, despite the fact that the two groups spent similar amounts of
      time in care (average time in care: 7 months). This finding held when the total
      placement cost was calculated using the State reimbursement rate of 206.00 US
      dollars per day for SAFE Home care (SH: 20,851 US dollars +/- 24,231 US dollars;
      FC: 8,441 US dollars +/- 21,126 US dollars, p < .001), and a conservative SAFE
      Home program fee of 85.00 US dollars per day that only considered the child care
      and custodial staffing costs uniquely associated with the program (SH: 13,314 US
      dollars +/- 21,718 US dollars; FC: 8,441 US dollars +/-21,126 US dollars, p <
      .001). CONCLUSION: Improvements in outcomes related to continuity of care can be
      attained through staff training. The SAFE Home model of care is not cost
      effective for first-time placements.

PMID- 15979707
TI  - The relationship between sexual abuse during childhood and parenting outcomes:
      modeling direct and indirect pathways.
AB  - OBJECTIVE: This study examined the association between childhood sexual abuse
      (CSA) and parenting outcomes including parenting stress, feelings of competence
      and discipline strategies. Maternal depression and current partner violence were
      hypothesized to be mediators of the association between CSA and parenting.
      METHOD: This study is based on secondary data analysis of archived data. The
      participants were 263 primiparous mothers (107 with a history of CSA and 156
      comparison mothers recruited from a prenatal clinic prior to the birth of their
      first child. Mothers were interviewed twice: once when they were between 28 and
      32 weeks gestation and again when their child was between 2 and 4 years of age.
      During the first interview, women were asked about childhood experiences of
      sexual abuse. During their second interview, they were asked about current
      symptoms of pathology and experiences with partner violence and parenting beliefs
      and practices. RESULTS: Structural Equation Modeling indicated that the
      relationship between CSA and punitive discipline was mediated by maternal
      depression and current partner violence. CSA was associated with higher maternal
      depression and higher partner violence. CSA, maternal depression, and current
      partner violence were associated with more negative parental perceptions and
      higher punitive discipline. Once maternal depression and current partner violence
      were in the model, the relationship between CSA and parenting outcomes was no
      different from zero. CONCLUSION: These results highlight the risks associated
      with CSA for parenting outcomes and suggest two potential pathways for this
      increased risk.

PMID- 15979708
TI  - Perceptions of parenting versus parent-child interactions among incest survivors.
AB  - OBJECTIVES: Although women with histories of child sexual abuse (CSA) perceive
      themselves as less competent mothers and report greater parenting difficulties
      than nonabused women, few investigators have actually observed the parenting
      behaviors of CSA survivors. The primary aim of this study was to examine whether
      incest history was related to maternal perceptions of parenting efficacy and
      interactional patterns with their children. The secondary aim of this study was
      to explore the constructs of internal working models of relationships and
      maternal psychological adjustment as potential mediators of the relation between
      incest history and parenting. METHODS: A community sample of 17 incest survivors,
      18 nonabused women and their 3-6 year-old children participated. Mothers
      completed self-report measures of parenting efficacy, parental bonding (i.e.,
      internal working models of relationships), and psychological adjustment. In
      addition, mothers interacted with their children in a problem-solving task.
      RESULTS: Although incest survivors reported less parenting self-efficacy than did
      nonabused mothers, their interactional styles with their children were positive
      overall and comparable to those of nonabused mothers. Specifically, survivors
      displayed moderate to high levels of support, assistance, and confidence, and
      their children showed high levels of affection towards their mothers. Incest
      survivors reported less bonding with their own mothers in childhood and poorer
      current psychological adjustment. CONCLUSIONS: Findings suggest that incest
      survivors' perceptions of their parenting abilities may be more negative than
      their actual parenting behaviors.

PMID- 15979709
TI  - The relationships of dissociation and affective family environment with the
      intergenerational cycle of child abuse.
AB  - OBJECTIVE: The purpose was to test a model that may explain how physically abused
      children become physically abusive parents. It was predicted that when the
      family's affective environment is uncohesive, unexpressive, and conflictual, a
      history of abuse experiences would be associated with elevated dissociation. It
      was hypothesized that dissociation would mediate between a childhood history of
      abuse and the current potential to be physically abusive. METHOD: Abuse history,
      affective environment in the family-of-origin, dissociation, and abuse potential
      were assessed in a sample of 76 mothers with elementary school-age children.
      RESULTS: Predictions were supported. Affective Family Environment moderated the
      relation between abuse history and dissociation, with abuse history relating to
      greater dissociation primarily when the family environment was conflictual,
      uncohesive and unexpressive. Further, dissociation significantly mediated the
      relation between abuse history and abuse potential (Z = 2.19, p < .05).
      CONCLUSIONS: Dissociation's strong association with abuse potential may partially
      explain why only some abused children later perpetuate the cycle of abuse, as
      those who are not dissociative into adulthood are likely to have lower abuse
      potential, in contrast to those displaying elevated dissociation. The extent of
      the dissociation may depend on the affective family environment in which the
      abuse took place.

PMID- 15979710
TI  - Build-a-Person Technique: an examination of the validity of human-figure features
      as evidence of childhood sexual abuse.
AB  - OBJECTIVE: This exploratory study examined the discriminant validity of 10 human
      figure features commonly used by many proponents of the draw-a-person (DAP)
      projective technique as evidence of childhood sexual abuse. Two exploratory
      features were also examined. METHOD: Rather than drawing human figures, 64
      children (M = 8 years, 9 months), including 19 sexually abused children, 26
      nonsexually abused but emotionally/behaviourally troubled children, and 19
      nonabused, nonclinical children, were instructed to build male and female figures
      using groups of prefabricated pieces of human-figure body parts. Unbeknownst to
      the children, each group of parts contained a potential sexual abuse feature (or
      features). RESULTS: None of the human-figure features under examination, either
      individually, or in combination, distinguished the sexually abused group from the
      other two groups of children. CONCLUSIONS: In accordance with years worth of DAP
      projective technique research, no support for the validity of the human-figure
      features under examination as evidence of childhood sexual abuse, was found.

PMID- 15979711
TI  - A critical review of available data on sexual abuse of children in Denmark.
AB  - OBJECTIVE: To describe different data sources that may illuminate the incidence
      and character of child sexual abuse (CSA) in Denmark in the late 1990s. METHOD:
      Data concerning alleged sexual abuse of children below 15 years of age in the
      1990s were retrieved from the Danish National Patient Register and the Danish
      National Criminal Register. In addition, all police files concerning reported CSA
      in 1 year (1998), were reviewed. RESULTS: The average annual incidence of CSA was
      .06 per 1,000 children, based on data in the National Patient Register; however,
      it was .5 per 1,000 based on data in the Criminal Register. In the Criminal
      Register, significant annual differences were found in cases of sexual offence
      against children below 12 years. The police reports comprised very comprehensive
      information about the victims and the character of CSA. Based on this information
      the incidence of police reported CSA in 1998 was 1.0 per 1,000 children, and .6
      per 1,000 excluding reported cases of indecent exposure. Half of intra-familial
      CSA resulted in a conviction compared to 40% of extra-familial CSA and 16% of
      indecent exposure. CONCLUSIONS: In Denmark, criminal statistics contain the most
      systematic collection of data on CSA. However, data reflect the reporting
      behavior by parents or other closely related adults, which may be influenced by
      changes in public awareness of the problem. Consequently, register data should be
      supplemented by data obtained from self-reported surveys on CSA.

PMID- 15979712
TI  - A meta-analysis of the relationship of child sexual abuse to HIV risk behavior
      among women.
AB  - OBJECTIVE: This study is a meta-analysis of the literature exploring the
      relationship between child sexual abuse (CSA) and HIV risk behavior among women.
      Four outcome variables were tested: unprotected sex; sex with multiple partners;
      sex trading; and adult sexual revictimization. METHOD: Forty-six studies met the
      inclusion criteria and were included in the analysis, and separate meta-analyses
      were performed for each of the four dependent variables described above. RESULTS:
      Using the correlation coefficient r as an effect size estimate, results indicate
      an average effect size of .05 for the unprotected sex meta-analysis (N = 16
      studies), .13 for the sex with multiple partners meta-analysis (N = 23 studies),
      .12 for the sex trading meta-analysis (N = 23 studies), and .17 for the adult
      sexual revictimization meta-analysis (N = 21 studies). We conducted a test of
      three potential moderator variables (source of sample, definition of CSA based on
      type of contact, and definition of CSA based on maximum age of victim). Results
      did not support the hypothesis that these three variables explain a significant
      amount of variability in effect sizes with one exception: Studies that define CSA
      more broadly to include adolescent victims (e.g., victims up to 17 years of age)
      had larger and more homogenous effect sizes for the sex trading meta-analysis
      than those that defined CSA as having occurred at younger ages. CONCLUSIONS:
      These findings suggest a small positive relationship between CSA and subsequent
      HIV risk behavior among women that varies as a function of how CSA and HIV risk
      behavior are operationalized.

PMID- 15979713
TI  - The use of predatory soil mites in ecological soil classification and assessment
      concepts, with perspectives for oribatid mites.
AB  - Gamasina are the main predators among the soil mesofauna and, therefore, have a
      crucial position in the soil food web and contribute significantly to energy and
      matter turnover. Ecological concepts including predatory mites in soil assessment
      have not yet been established, while standardized sampling, extraction, and
      conservation methods are available. There are reliable keys for Europe that cover
      most families. Few species in low dominance ranks correlate well with soil
      properties like soil texture and pH. Meaningful endpoints for soil assessment are
      community parameters that are based on the life history of the species (e.g.,
      Maturity Index). It has been shown that the predatory mites, as well as the
      oribatids as a second common and widespread group of mites, fit well into a soil
      assessment concept comparable to RIVPACS, which was established for aquatic
      systems. Perspectives for future research are the development of a computer-aided
      identification key and the creation of a database with information on the ecology
      and biogeography of important species.

PMID- 15979714
TI  - Critical analysis of radiochemical methodologies for the assessment of sediment
      pollution and dynamics in the lagoon of Venice (Italy).
AB  - Aquatic sediments are the ultimate sink of wastes dispersed in freshwater and
      soil. They are therefore a useful tool for investigating polluted ecosystems.
      Lagoon environments are very difficult to study due to their unstable morphology.
      Under these circumstances, even an excellent environmental investigation of a
      restricted lagoon area would still be inadequate to appreciate the
      characteristics of the entire system. The Venice lagoon is a very complex
      ecosystem whose morphology is complicated further by extensive anthropic
      intervention. A good environmental representation of the area was obtained with a
      preliminary radiochemical survey of airborne radionuclides, a unique tool in
      evaluating the homogeneity of the entire sedimentary system. It must be stressed,
      however, that the significance of the data depends substantially on the use of
      qualified procedures. Based on this, a detailed study was carried out on selected
      homogeneous areas, reconstructing the inventories and fluxes of pollutants in the
      sediments. In this work the radiochemical approach to the environmental study of
      the Venice lagoon is examined.

PMID- 15979715
TI  - Pollutant loads from the drainage basin to the Venice Lagoon (Italy).
AB  - In order to assess the actual pollutant loads from the drainage basin, the twelve
      major tributaries of the Venice Lagoon were monitored and studied in the period
      1998-2000 in the framework of the DRAIN project. A specific sampling scheme was
      designed to investigate the effects of the different regimes, including floods,
      in the transport of total and dissolved metals, nitrogen and phosphorous species
      as well as organic micropollutants. The loads were calculated from data collected
      during the year of 1999, since this year displayed a value close to the mean in
      terms of the distribution of total rainfall on the drainage basin. The annual
      values for the different pollutants are reported and discussed. A comparison with
      the estimates of previous investigations highlights the significant advancement
      provided by the DRAIN project results in the understanding of the drainage basin
      contribution to the pollution of the lagoon. Finally, the importance of flood
      events on the overall balance of materials and pollutants delivered to the lagoon
      is emphasized.

PMID- 15979716
TI  - Evidence of genetic damage in grass gobies and mussels from the Venice lagoon.
AB  - The presence of genetic damage has been investigated in two native species of the
      Venice lagoon: the common mussel Mytilus galloprovincialis and the grass goby
      Zosterisessor ophiocephalus. Two sampling campaigns were performed in summer 1998
      and 1999. Aromatic-like DNA adducts were analysed in selected tissues of gobies
      and mussels by using the 32P-postlabelling assay. In 1999, micronuclei and other
      nuclear abnormalities were additionally scored on gill cells and haemocytes of
      individual mussels whereas inorganic (As, Cd, Cr, Hg, Ni, Pb, Sn) as well as
      organic contaminants (polycyclic aromatic hydrocarbons, polychlorinated biphenyls
      and other chlorinated compounds) were measured in the total mussel pulp. Compared
      to the lagoon inlet area, gobies and mussels from the industrial district
      (Marghera) showed significant DNA adduct levels and increased frequencies of
      cytogenetic alterations (evidence of genetic damage was absent or inconsistent in
      other sites). The substantial levels of aromatic and chlorinated contaminants
      detected in mussels from Marghera also support the exposure of native organisms
      to genotoxic agents.

PMID- 15979717
TI  - Short and medium chain length chlorinated paraffins in UK human milk fat.
AB  - Chlorinated paraffins (also called polychlorinated n-alkanes -- PCAs) are a class
      of industrial chemicals comprising chlorinated straight chain hydrocarbons. They
      have a wide range of applications and are now found in a range of environmental
      compartments. We analysed a total of 25 human milk-fat samples, donated by 18
      individuals from the urban London and more rural Lancaster areas in the UK, for
      short chain PCAs (C(10)-C(13) sPCAs) and medium chain PCAs (C(14)-C(17) mPCAs),
      using gas chromatography-ECNI high-resolution mass spectrometry. Our study
      confirms that trace quantities of PCAs can reach human milk-fat. sPCAs were
      detected in all but four samples, while mPCAs were detected in all samples. The
      median sPCA concentration was 180 ng/g fat (range of 49 to 820 ng/g fat --
      detected values only) and the median mPCA concentration was 21 ng/g fat (range of
      6.2 to 320 ng/g fat). No differences were noted in ranges of observed values for
      either sPCAs or mPCAs between samples from London and Lancaster. Most samples
      also exhibited similar patterns of sPCAs and mPCAs. One sample exhibited a
      different pattern for sPCAs and mPCAs, an observation that may be related to
      differences in exposure or biological factors for this individual.

PMID- 15979718
TI  - Polychlorinated diphenyl ethers (PCDEs): environmental levels, toxicity and human
      exposure: a review of the published literature.
AB  - This paper reviews the state of the science regarding polychlorinated diphenyl
      ethers (PCDEs), a group of halogenated aromatic compounds, which are structurally
      related to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans
      (PCDFs). Special attention is paid to the environmental levels, toxicity, and
      human exposure. PCDEs have been detected in a number of environmental samples,
      and their widespread occurrence in the environment is mainly the result of their
      presence as impurities in chlorophenol preparations. In humans, PCDE congeners
      have been detected in adipose tissue. As for other persistent organic pollutants
      (POPs), dietary intake is very probably the main route of exposure to PCDEs for
      the general population. However, data concerning PCDE levels in foodstuffs are
      very limited. It is concluded that investigations on experimental toxicity,
      dietary intake, and potential human health effects of PCDEs are clearly
      necessary.

PMID- 15979719
TI  - Air pollution and young children's inhalation exposure to organophosphorus
      pesticide in an agricultural community in Japan.
AB  - Assessment of airborne organophosphorus pesticides in houses of young children (1
      6 years old) and childcare facilities was conducted following pesticide
      applications in an agricultural community in Japan. Trichlorfon and fenitrothion,
      applied in two separate periods, were frequently detected from outdoor and indoor
      air. Dichlorvos, the primary degradation product of trichlorfon, was also
      detected after the application of trichlorfon. Both the outdoors and indoor
      concentration of applied pesticide were shown to increase with decreasing
      distance from the pesticide-applied farm. Indoor concentration of these
      pesticides significantly correlated with outdoor concentration (p=0.001 for
      trichlorfon and p=0.001 for fenitrothion), indicating infiltration of applied
      pesticide inside. Ratio of indoor to outdoor concentration (I/O ratio) of
      fenitrothion was higher for houses with windows open during the application than
      those with closed windows (median value: 0.74 vs. 0.16, p=0.003). However, a
      similar trend was not observed for trichlorfon as well as dichlorvos in the first
      period. Dichlorvos was found to have a higher I/O ratio than trichlorfon during
      the period, and clear correlation between indoor concentrations of dichlorvos and
      those of trichlorfon suggested increased decomposition of trichlorfon in the
      indoor environment. Daily inhalation exposure estimated by using the fixed
      measurement data and time-activity questionnaire ranged from 0 to 35 ng/kg/day
      for trichlorfon, from 0 to 26 ng/kg/day for dichlorvos, and from 0 to 44
      ng/kg/day for fenitrothion. Median inhalation exposure from indoor air accounted
      for 74%, 86.3%, and 45% of the daily inhalation exposure, respectively. For
      kindergarteners or nursery school children, inhalation exposure at childcare
      facilities was comparable with or more than that at home, indicating that
      pollution level at childcare facilities had potential of high impact on
      children's exposure. Estimated daily inhalation exposures were inversely
      correlated to the proximity of their activity location to the pesticide-applied
      farm.

PMID- 15979720
TI  - Soil As contamination and its risk assessment in areas near the industrial
      districts of Chenzhou City, Southern China.
AB  - In order to assess soil As contamination and potential risk for human, soil,
      paddy rice, vegetable and human hair samples from the areas near the industrial
      districts in Chenzhou, southern China were sampled and analyzed. The results
      showed that the anthropogenic industrial activities have caused in local
      agricultural soils to be contaminated with As in a range of 11.0-1217 mg/kg. The
      GIS-based map shows that soil contamination with As occurred on a large scale,
      which probably accounted for up to 30% of the total area investigated. Soil As
      concentration abruptly decreased with an increase in the distance from the
      polluting source. High As concentrations were found in the rice grain that ranged
      from 0.5 to 7.5 mg/kg, most of which exceed the maximal permissible limit of 1.0
      mg/kg dry matter. Arsenic accumulated in significantly different levels between
      leafy vegetables and non-leafy vegetables. Non-leafy vegetables should be
      recommended in As-contaminated soils, as their edible parts were found in
      relatively low As level. Arsenic concentrations in 95% of the total human hair
      samples in the contaminated districts were above the critical value, 1.0 mg/kg,
      set by the World Health Organization. Arsenic could be enriched in human hair to
      very high levels without being affected by As containing water. The results
      revealed that the soils and plants grown on them are major contributors to
      elevate hair As in the industrial population. Therefore, the potential impact on
      human health of ingestion/inhalation of soil As around the industrial districts
      seems to be rather serious. Hence proper treatments for As contaminated soils are
      urgently needed to reduce the contamination.

PMID- 15979722
TI  - Good fish/bad fish: a composite benefit-risk by dose curve.
AB  - Balancing risks and benefits of fish consumption is now a high visibility public
      health topic. Many studies identify health benefits of eating fish, both for
      prenatal development and adult cardiovascular conditions, partly attributed to
      omega-3 (n-3) polyunsaturated fatty acids or PUFAs). Many reports raise concerns
      about methylmercury and polychlorinated biphenyl effects on the developing fetal
      brain (although adults, too, can manifest methylmercury effects). Most reports
      and advisories focus on recreational or subsistence fish, but the vast majority
      of people obtain most or all of their fish from commercial sources. Our analysis
      of the nine most common fish in New Jersey markets, yielded a weighted average
      methylmercury concentration of 0.23 ug/g (ppm wet weight). There are great
      disparities in the amount and distribution of both PUFAs and contaminants) in
      different fish species. Recognizing that both benefits and harm must be related
      to dose, we propose a compound dose-response curve, currently based on limited
      data, to identify a zone of benefit, above the benefit threshold and below the
      harm threshold. The duration of pregnancy and birth weight improve at a benefit
      threshold of about 8-15 g/day maternal fish intake. Meta-analyses reveal adult
      cardiovascular benefits around 7.5-22.5 g/day bracket (assuming an 8 ounce/227 g
      typical meal), yielding a midpoint also at 15 g/day, but this is an artifact of
      the intake stratification. Benefit asymptotes are harder to extract, but are
      above 45 g/day, and in some studies exceed 100g/day. Using the EPA Reference Dose
      of 0.1 ug/kg day as a methylmercury threshold, The fish intake threshold for harm
      converts to 27 g/day (for a selection of common commercial fish averaging 0.23
      ppm MeHg) to 65 g/day for someone choosing fish low in MeHg (0.1 ppm). However,
      these are worst case thresholds since the RfD includes uncertainty factors. Some
      people eat much more than 65 g/day. The shape of the dose-benefit and dose-harm
      curves require better data for estimating thresholds and asymptotes, which will
      impact the composite curve. We propose this approach clarifies the kinds of data
      needed to improve risk communication on "what should I eat". Benefits from fish
      consumption are confounded by socioeconomic class and/or by the avoidance of more
      harmful foods that fish replaces, which may be as important a benefit mechanism
      as the PUFA content. Additional studies with better dose-reconstruction are
      needed and large scale intervention studies are desirable.

PMID- 15979723
TI  - Emerging concepts and therapeutic implications of beta-adrenergic receptor
      subtype signaling.
AB  - The stimulation of beta-adrenergic receptor (betaAR) plays a pivotal role in
      regulating myocardial function and morphology in the normal and failing heart.
      Three genetically and pharmacologically distinct betaAR subtypes, beta1AR,
      beta2AR, and beta3AR, are identified in various types of cells. While both
      beta1AR and beta2AR, the predominant betaAR subtypes expressed in the heart of
      many mammalian species including human, are coupled to the Gs-adenylyl cyclase
      cAMP-PKA pathway, beta2AR dually activates pertussis toxin-sensitive Gi proteins.
      During acute stimulation, beta2AR-Gi coupling partially inhibits the Gs-mediated
      positive contractile and relaxant effects via a Gi-Gbetagamma-phosphoinositide 3
      kinase (PI3K)-dependent mechanism in adult rodent cardiomyocytes. More
      importantly, persistent beta1AR stimulation evokes a multitude of cardiac toxic
      effects, including myocyte apoptosis and hypertrophy, via a calmodulin-dependent
      protein kinase II (CaMKII)-, rather than cAMP-PKA-, dependent mechanism in rodent
      heart in vivo and cultured cardiomyocytes. In contrast, persistent beta2AR
      activation protects myocardium by a cell survival pathway involving Gi, PI3K, and
      Akt. In this review, we attempt to highlight the distinct functionalities and
      signaling mechanisms of these betaAR subtypes and discuss how these subtype
      specific properties of betaARs might affect the pathogenesis of congestive heart
      failure (CHF) and the therapeutic effectiveness of certain beta-blockers in the
      treatment of congestive heart failure.

PMID- 15979724
TI  - MEKC-LIF of gamma-amino butyric acid in microdialysate: systematic optimization
      of the separation conditions by factorial analysis.
AB  - Micellar electrokinetic chromatography allows the efficient separation of
      biogenic amines and amino acids in biological samples. Analytes of interest,
      sample composition, and sample matrix may vary between studies, which
      necessitates optimization of separations to meet the requirements and conditions
      of an experiment. Factorial analysis is an efficient tool to accomplish this type
      of optimization involving multiple interacting factors. The present study
      describes an optimization procedure for separation of the inhibitory
      neurotransmitter GABA utilizing capillary electrophoresis with laser induced
      fluorescence detection. Standards labeled with the flourogenic reagent 3-(2
      furoyl)quinoline-2 carboxaldehyde were separated with varying concentrations of
      borate buffer, beta-cyclodextrin, sodium dodecyl sulfate and pH. The optimized
      separation method had a correlation coefficient between concentration of GABA and
      fluorescent signal of 0.98, and was linear in the desired concentration range of
      25 nM-10 microM. Glutamic acid, aspartic acid and taurine were also quantified
      using this separation. When applied to microdialysate collected from the region
      of the suprachiasmatic nucleus, this separation was able to measure daily
      variations in GABA levels. The factorial design experiment has proven to be a
      useful tool, allowing adjustments in the separation of neurotransmitters based on
      individual requirements.

PMID- 15979725
TI  - Identifying "paradigm failures" contributing to treatment-resistant depression.
AB  - BACKGROUND: "Treatment resistant depression" is likely to emerge from a number of
      factors, including application of the wrong diagnostic and treatment models.
      METHOD: Current paradigms for managing both depression and treatment resistant
      depression are considered. We then examine the prevalence of a set of paradigm
      failures that appeared to contribute to treatment resistant depression in
      outpatients of a tertiary referral Mood Disorders Unit. RESULTS: Six illustrative
      paradigm failures are described and their frequencies within the clinical sample
      reported. Identified paradigm failures were diagnosing and/or managing a non
      melancholic condition as if it were melancholic depression, failure to diagnose
      and manage bipolar disorder, psychotic depression or melancholic depression,
      misdiagnosing secondary depression and failure to identify organic determinants.
      CONCLUSION: We suggest that the identification of such "paradigm failures"--and
      of others that can be assumed to operate--has the potential to enrich the
      assessment and management of depressed patients, and reduce the prevalence of
      treatment resistance.

PMID- 15979726
TI  - Interleukin-6 and dexamethasone modulate in vitro asymmetric antibody synthesis
      and UDP-Glc glycoprotein glycosyltransferase activity.
AB  - The increased production of asymmetric IgG protective antibodies is one of the
      mechanisms proposed to explain a successful semiallogeneic pregnancy. We have
      previously demonstrated that IL-6 was able to enhance the synthesis of these
      antibodies by a murine hybridoma, while the glucocorticoid dexamethasone (DEXA)
      diminished it. In order to investigate the mechanism of asymmetric antibody
      synthesis, we investigate the role of UDP-Glc glycoprotein glucosyltransferase
      (GT), an endoplasmic reticulum enzyme involved in the quality control and folding
      of glycoproteins. Either recombinant murine rmIL-6 (0-10-40-160-320-640 ng/ml) or
      DEXA (0.15 microM) were added to a mouse hybridoma culture and incubated for 24
      and 72 h in the first case, and for 4h in the presence of DEXA. Anti-DNP
      asymmetric antibodies were determined in the culture supernatants by ELISA. After
      harvesting, hybridoma cells were sonicated and GT activity was analysed in
      isolated microsomal fractions by measuring UDP((14)C)-Glc incorporation into urea
      denatured thyroglobulin (urea-Tg). In the present paper, we showed that IL-6,
      mainly at 40 ng/ml and t=24h, was able to upregulate both in vitro GT activity
      (+74%) and asymmetric molecule synthesis (+227%). Lower increases were obtained
      employing 10 and 160 ng/ml. On the other hand, DEXA, at 0.15 microM and t=4h,
      showed a mild inhibition of enzyme activity (-10%) and a diminished proportion of
      asymmetric IgG (-49%). A direct relationship between GT activity and proportion
      of the asymmetric antibody synthesised was found in our hybridoma cells employing
      IL-6 and DEXA in different conditions, as was indicated by a correlation
      analysis. These results suggest that GT might be involved in the synthesis of
      asymmetric antibodies.

PMID- 15979727
TI  - Morphine-induced changes in the activity of proopiomelanocortin and prodynorphin
      systems in zymosan-induced peritonitis in mice.
AB  - We have shown that supplementation of proinflammatory agent with a high dose of
      morphine not only abolishes inflammation-related pain symptoms but also inhibits
      influx of leukocytes to the inflamed peritoneal cavity. Present investigations
      focused on effects of morphine on proopiomelanocortin and prodynorphin systems
      during zymosan-induced peritonitis. Males of SWISS mice were ip injected with
      zymosan (Z, 40 mg/kg) or zymosan with morphine (ZM, 20 mg/kg). At time 0
      (controls) and 4 and 24h after stimulation, peritoneal leukocytes (PTLs) were
      counted, PTL levels of opioid peptides (beta-endorphin and dynorphin) measured by
      radioimmunoassays, while mRNAs coding their respective precursors (POMC and PDYN)
      and receptors (MOR and KOR) determined by QRT-PCR. Influx of inflammatory PTLs,
      mainly PMNs, was significantly delayed by morphine co-injection. Total levels of
      beta-endorphin and dynorphin corresponded with PTL numbers, while levels per cell
      were similar in all groups except of beta-endorphin, decreased in ZM at 4h.
      Levels of both peptides in peritoneal fluid were increased in Z and ZM groups at
      4h, while at 24h only in case of beta-endorphin in Z group. POMC was increased
      only in ZM group at 4h of peritonitis, while PDYN in both Z and ZM groups at the
      same time. MOR mRNA was increased 24h after injection in Z and ZM groups, while
      KOR mRNA was similar in all groups except of decrease in Z at 24h. In conclusion,
      endogenous opioids and their receptors are involved in zymosan-induced
      peritonitis and affected in various ways by morphine co-injection.

PMID- 15979728
TI  - Ontogeny of cortical synaptic depression underlying olfactory sensory gating in
      the rat.
AB  - Sensory gating is the ability to filter irrelevant or redundant sensory input and
      is a critical function of all sensory systems that allows efficient processing of
      important stimuli. The present results demonstrate that a form of activity
      dependent synaptic depression recently found to be involved in both cortical and
      behavioral olfactory sensory gating, is functional by at least the first
      postnatal week in the rat piriform cortex, and shares a common metabotropic
      glutamate receptor mechanism.

PMID- 15979729
TI  - Purinergic receptor modulation of BV-2 microglial cell activity: potential
      involvement of p38 MAP kinase and CREB.
AB  - ATP is abundant in the extracellular fluid following brain injury, and it exerts
      potent modulatory effects on microglia, whose hyperactivation is thought to
      exacerbate neuronal damage. We show here that ATP decreases LPS-stimulated iNOS
      and COX-2 expression and reduces NO release in BV-2 microglia by a mechanism
      involving p38 MAP kinase. Further, we demonstrate that the inhibitory effects of
      ATP on NO production occur within 30 min of exposure and correlate with
      activation of the transcription factor CREB. Together, these data suggest that
      ATP may exert neuroprotective effects in the brain via a mechanism involving
      augmented activation of the p38/CREB pathway.

PMID- 15979730
TI  - Closure of persistent tracheocutaneous fistula following "starplasty"
      tracheostomy in children.
AB  - OBJECTIVE: The "starplasty" technique of pediatric tracheostomy was introduced in
      1990 as an alternative pediatric tracheostomy technique associated with several
      advantages. The only apparent drawback of this technique is the higher incidence
      of persistent tracheocutaneous fistula following decannulation. Several methods
      have been proposed for closure of persistent tracheocutaneous fistula in
      children, including fistulectomy with primary closure and fistulectomy with
      healing by secondary intent. Some authors advocate placement of a drain at the
      time of primary closure. We present our experience with closure of persistent
      tracheocutaneous fistula following starplasty in children over the past 15 years.
      METHODS: Ninety-six starplasty procedures were performed on 96 children from 1990
      to present, all by the senior author or under the guidance of the senior author.
      Twenty-eight of these children have been decannulated. Three fistulas closed
      spontaneously following decannulation. Of the remaining 25 children, 13 have
      undergone surgical closure of the tracheocutaneous fistula by the senior author.
      All tracheocutaneous fistula closures were performed as a fistulectomy with
      primary closure in three layers. Drains were not used in any of the patients.
      RESULTS: There were three minor complications in the postoperative period (wound
      infection and airway granuloma) and no major complications. None of the patients
      have experienced any degree of airway stenosis and there was no need for a repeat
      tracheotomy in any of the tracheocutaneous fistula closure patients. The cosmetic
      results were deemed to be good. CONCLUSIONS: "Starplasty" is a safe, reliable
      pediatric tracheostomy technique that has been shown to decrease the incidence of
      perioperative morbidity and mortality. The only drawback appears to be a high
      incidence of postoperative tracheocutaneous fistula. Our method of persistent
      tracheocutaneous fistula closure following starplasty is safe and effective, with
      no major complications and no incidence of postoperative airway narrowing.

PMID- 15979731
TI  - Tonsillitis index: an objective tool for quantifying the indications for
      tonsillectomy for recurrent acute tonsillitis.
AB  - This report is a preliminary exploration of the concept of a "Tonsillectomy
      Index" (TI) as an objective tool for quantifying the indications for
      tonsillectomy for recurrent acute tonsillitis (AT). The TI is derived by
      multiplying the number of episodes of AT by the number of years during which the
      episodes of AT occurred. Our objective in this study was to investigate whether
      there is a relationship between the natural history of AT, the immunological
      functions of tonsils and our proposed TI. For the natural history of AT, we
      medically followed 11 children with a history of AT for 5 years. When TI was
      equal to or greater than 8 (TI> or =8), the children suffered a significantly
      greater number of episodes of AT. For the immunological portion of our study, we
      enrolled 36 children and 46 adults undergoing tonsillectomy for either AT (study
      group) or tonsillar hypertrophy (control group, CG). We analyzed the co
      stimulatory signals, CD80 and CD86 on tonsillar B-lymphocytes. The expression
      rates of CD80 and CD86 in the AT group with TI> or =8 were significantly
      decreased compared to those with TI was less than 8 (TI<8), as well as with those
      in control (tonsillar hypertrophy) group. Our preliminary findings suggest that
      when the TI> or =8, the tonsils have deteriorated immunologically and spontaneous
      resolution of recurrent AT is less likely to occur, hence tonsillectomy is
      appropriate. TI may be a useful tool for surgical decision making.

PMID- 15979732
TI  - Clinical evaluation is insufficient for diagnosis of pediatric OSAS.

PMID- 15979733
TI  - Arteriovenous malformation of the nasopharynx: a case report.
AB  - Arteriovenous malformation (AVM) of the head and neck is a rare vascular anomaly
      but when present is persistent and progressive in nature and can represent itself
      truly as a lethal benign disease. We present here an unusual case of an AVM with
      the size of 1.5 cm x 0.8 cm at the adenoid tissue found in an 8-year-old boy,
      which is not previously reported in the literature where we treated the patient
      with surgery alone. Although bleeding is a common presentation with vascular
      malformations, we have not seen any bleeding in our case. After the surgery,
      paranasal sinus and neck CT were undertaken. They showed no other AVM.

PMID- 15979734
TI  - A practical classification of otitis media subgroups.

PMID- 15979735
TI  - The effect of preoperative dexamethasone on early oral intake, vomiting and pain
      after tonsillectomy.
AB  - OBJECTIVE: Postoperative morbidity in patients undergoing tonsillectomy with or
      without adenoidectomy includes inadequate oral intake, pain, nausea, vomiting and
      bleeding. The purpose of this study is to evaluate the effect of preoperative 0.5
      mg/kg i.v. dexamethasone on postoperative early oral intake, pain, vomiting in
      patients undergoing adenotonsillectomy while performing standard anesthesia
      technique and sharp dissection tonsillectomy. METHODS: In this prospective,
      double-blinded, placebo-controlled study 62 children, aged 4-12 years, who
      underwent tonsillectomy with or without adenoidectomy were randomly assigned to
      receive single dose of 0.5 mg/kg i.v. dexamethasone preoperatively. Patients
      started to receive 100 ml of clear fluids 2 h postoperatively, then were offered
      every hour. When pain score was 3 or above, paracetamol was given for pain
      control. Tolerating 400 ml of clear fluids, no bleeding and no vomiting were
      accepted as discharge criteria. The discharge time was also recorded. The
      incidence of early vomiting, pain scores, amount of oral intake were recorded
      until the discharge time. RESULTS: Compared with placebo, the patients who
      received preoperative dexamethasone had significantly less pain score during the
      first 6 h postoperatively (p<0.05), adequate amount of oral intake time was
      shorter (p<0.05) and the discharge time was earlier (p<0.05). No difference was
      found in vomiting incidence in both groups. CONCLUSION: Preoperative
      dexamethasone use significantly reduces early posttonsillectomy pain, improves
      oral intake and facilitates meeting the discharge criteria while using standard
      anesthesia technique and sharp dissection tonsillectomy without any significant
      side effects.

PMID- 15979736
TI  - Tag-array based HPV genotyping by competitive hybridization and extension.
AB  - A method is described for HPV genotyping based on multiplex competitive
      hybridization (MUCH) combined with apyrase mediated allele-specific extension
      (AMASE). Two type-specific oligonucleotides were designed for each of the 23
      investigated HPV types and directed towards two highly inter-type heterogeneous
      regions. The type-specific oligonucleotides were allowed to compete in the
      hybridization to an immobilized template resulting in a highly specific
      hybridization process. To increase further the specificity, a second step of type
      discrimination was used in which specific extension of 3'-termini matched
      oligonucleotides was performed. The 46 type-specific oligonucleotides each had a
      unique tag sequence to allow detection via an array of oligonucleotides
      complementary to the tags. To evaluate the genotyping assay, a total of 92 HPV
      positive samples were tested in this study. Twelve had double infections and five
      had three to five coexisting HPV types. The results show that MUCH-AMASE can
      readily detect multiple infections, whereas conventional dideoxy sequencing
      resulted in ambiguous sequence. Four samples with three to five genotypes
      detected were cloned and individual clones were sequenced. The cloning procedure
      verified the MUCH-AMASE results with indications that we can find minor
      infections (<2% relative amounts). We can thus conclude that the developed assay
      is highly sensitive, with improved throughput and with excellent possibility to
      detect multiple infections.

PMID- 15979737
TI  - Gene expression profiles associated with the transition to parasitism in
      Ancylostoma caninum larvae.
AB  - Ancylostoma caninum is a common canine parasite responsible for anemia and death
      in infected dogs. Gene expression profiling was used to investigate molecular
      differences between two different forms of the third larval stage (L3s):
      infective free-living larvae and in vitro serum-stimulated larvae that mimic the
      initial stages of parasitism of a host. We developed an A. caninum cDNA
      microarray consisting of 4191 EST clones, and used it to identify a set of 113
      genes that are differentially regulated between infective and parasitic larval
      stages. Real-time RT-PCR was used to confirm the expression differences of a
      subset of the genes. Of the genes repressed upon serum stimulation, seven encode
      members of the 'Ancylostoma secreted protein' ASP family, while another
      transcript encoding a 24 kDa excretory protein with similarity to ASP was up
      regulated in serum-stimulated L3s. This suggests that different members of a
      protein family that has important implications for the hookworm's parasitic
      lifestyle are regulated in a complementary manner in response to serum
      stimulation. Comparison of two strains of A. caninum from North Carolina and
      Maryland only identified a single gene, one of the members of the ASP family,
      that was differentially repressed upon serum stimulation.

PMID- 15979738
TI  - Chagas disease and anticardiolipin antibodies in older adults.
AB  - Infectious agents have been implicated in the induction of antiphospholipid
      antibodies and the development of antiphospholipid antibody syndrome. The
      objective of this study was to evaluate the association of anticardiolipin
      antibodies with Chagas' disease antibodies. A total of 45 patients, who were
      positive for Chagas' disease (American Trypanosomiasis) antibodies and had
      elevated levels of anticardiolipin antibodies, were investigated in a case
      control study. Twenty-four of the patients were male and 21 female with ages
      ranging from 60 to 81 years and with a mean age of 68.3 years. Twenty-three
      female and 11 male individuals from a senior citizen support group who were
      apparently healthy formed a control group. Their ages varied from 62 to 80 years
      with a mean of 68 years. The measurement of anticardiolipin antibodies was
      performed by means of enzyme-linked immunoabsorbent assay (ELISA) for
      quantitative measurement of IgG and IgM antibodies against cardiolipins in serum
      and evaluation of Chagas' disease was confirmed by the Machado Guerreiro test.
      Statistical analysis was made using Fisher's exact test with a confidence
      interval of 95% and a p-value <0.05. Elevated levels of anticardiolipin
      antibodies were detected in 48.8% of the patients and in 26.4% of the control
      group giving a p-value <0.038 using the Fisher's exact test. Thus, an association
      between Chagas' disease antibodies and anticardiolipin antibodies was evidenced
      in this series of patients.

PMID- 15979739
TI  - Depression, activities of daily living, and quality of life of community-dwelling
      elderly in three Asian countries: Indonesia, Vietnam, and Japan.
AB  - The purpose of this study was to examine the prevalence of screening-based
      depression and the association of depression with activities of daily living
      (ADL) and quality of life (QOL) of community-dwelling elderly in the developing
      and developed countries. A total of 2,695 community-dwelling elderly subjects
      aged 60 years or older living in five rural Asian towns (Indonesia: 411, Vietnam:
      379, Japan: 1,905) participated in this cross-sectional study. Depressive
      symptoms were assessed using a 15-item geriatric depression scale (GDS-15). ADL,
      higher daily activities, and medical and social history were assessed by
      interviews or self-report questionnaires. For the assessment of subjective QOL, a
      100mm visual analogue scale was used. Using a cut-point of 5/6 for the GDS-15,
      782 participants (29.0%) appeared to have depression (Indonesia: 33.8%, Vietnam:
      17.2%, Japan: 30.3%). Subjects with depression had significantly lower scores for
      both ADL and QOL than those without depression in all the three countries. In all
      the three countries, 17.2-33.8% of community-dwelling elderly subjects had
      screening-based depression, which was commonly associated with both lower
      quantitative ADL and lower QOL.

PMID- 15979740
TI  - Occurrence of lung tumor between internal thoracic arterial and saphenous vein
      grafts to coronary arteries demonstrated by multislice computed tomography.

PMID- 15979741
TI  - A case of ST-segment elevation provoked by distended stomach conduit.
AB  - A case of ST-segment elevation provoked by distended stomach conduit is
      presented. An 83-year-old woman was admitted to our hospital with worsening chest
      discomfort. She had a previous history of subtotal esophagectomy, which was
      reconstructed using a stomach conduit in the posterior mediastinum.
      Electrocardiogram showed ST-segment elevation in the inferior leads and a
      prominent negative P wave in lead V1. Echocardiography demonstrated normal left
      ventricular function without regional wall motion abnormality; however, the left
      atrium and ventricle compressed by a substantially distended stomach conduit was
      noted. Subsequent angiocardiography revealed no coronary atherosclerotic stenosis
      and normal contractility of the left ventricle. Chest symptoms resolved soon
      after nasogastric suction, leading to resolution of electrocardiographic changes.
      The stomach conduit diminished on following repeated echocardiography. The
      patient was discharged without any evidence of myocardial infarction. Esophagus
      disease of the reconstructed stomach conduit should be recognized as a rare but
      considerable cause for electrocardiographic changes.

PMID- 15979742
TI  - Can family caregiving substitute for nursing home care?
AB  - Informal care should be a substitute for nursing homes but empirical evidence
      often suggests the opposite. This may be because informal care receipt is
      positively correlated with unobserved negative health characteristics. We exploit
      variation in children's characteristics as instruments for informal care to
      provide Two-Stage Least Squares (TSLS) estimates of nursing home use among a
      sample of 6855 individuals from the 1993-2000 waves of the AHEAD survey. While
      OLS results suggest informal care is associated with greater future nursing home
      risk, TSLS estimates show that receipt of informal care statistically and
      substantially reduces the risk of nursing home entry. This finding has
      implications for Medicaid and private long-term care insurance markets.

PMID- 15979743
TI  - Direct identification of slowly growing Mycobacterium species by analysis of the
      intergenic 16S-23S rDNA spacer region (ISR) using a GelCompar II database
      containing sequence based optimization for restriction fragment site
      polymorphisms (RFLPs) for 12 enzymes.
AB  - To obtain Mycobacterium species identification directly from clinical specimens
      and cultures, the 16S-23S rDNA spacer (ISR) was amplified using previously
      published primers that detect all Mycobacterium species. The restriction enzyme
      that could potentially produce the most restriction fragment length polymorphisms
      (RFLPs) was determined from all available ISR DNA sequences in GenBank to produce
      a novel data set of RFLPs for 31 slowly growing Mycobacterium species.
      Subsequently a GelCompar II database was constructed from RFLPs for 10 enzymes
      that have been used in the literature to differentiate slowly growing
      Mycobacterium species. The combination of Sau96I and HaeIII were the best choice
      of enzymes for differentiating clinically relevant slowly growing Mycobacterium
      species. A total of 392 specimens were studied by PCR with 195 negative and 197
      positive specimens. The ISR-PCR product was digested with HaeIII (previously
      reported) and Sau96I (new to this study) to obtain a Mycobacterium species
      identification based on the ISR-RFLPs. The species identification obtained by ISR
      RFLP was confirmed by DNA sequencing (isolate numbers are shown in parentheses)
      for M. avium (3), M. intracellulare (4), M. avium complex (1), M. gordonae (2)
      and M. tuberculosis (1). The total number of specimens (99) identified were from
      culture (67), Bactectrade mark 12B culture bottles (11), EDTA blood (3), directly
      from smear positive specimens (13), tissue (4) and urine (1). Direct species
      identification was obtained from all 13/13 smear positive specimens. The total
      number of specimens (99) were identified as M. tuberculosis (41), M. avium (7),
      M. avium complex (11), M. intracellulare MIN-A (20), M. flavescens (2), M.
      fortuitum (10), M. gordonae (4), M. shimoidei (1), M. ulcerans (1) and M.
      chelonae (2). This method reduces the time taken for Mycobacterium species
      identification from 8-10 weeks for culture and biochemical identification; to 4-6
      weeks for culture and ISR-RFLP; to 2 days for smear-positive specimens by ISR
      RFLP. The precise 2 day identification obtained may provide significant
      advantages in clinical management.

PMID- 15979744
TI  - Development of a group-specific PCR combined with ARDRA for the identification of
      Bacillus species of environmental significance.
AB  - A group-specific primer pair was designed to amplify the 16S rRNA gene of
      representative reference strains from environmentally sourced, mesophilic aerobic
      spore-forming Bacillus taxa. The PCR generated a 1114 bp amplicon but did not do
      so with DNA extracted from 16 other Eubacterial species. When amplicons were
      digested with restriction enzymes AluI or TaqI, different profiles containing
      between 2 and 5 fragments ranging in size from 76 to 804 base pairs were seen
      with different Bacillus species. This procedure, known otherwise as amplified
      ribosomal DNA restriction analysis or ARDRA, produced unique and distinguishable
      patterns to differentiate between 15 ATCC reference strains (10 Bacillus, 3
      Paenibacillus and 2 Brevibacillus member species) as well as 3 misidentified
      Bacillus probiotic strains in a commercial collection. Our simplified PCR-ARDRA
      protocol provides a facile method for the identification of most environmentally
      important species of Bacillus.

PMID- 15979745
TI  - Use of a spectrophotometric bioassay for determination of microbial sensitivity
      to manuka honey.
AB  - The antimicrobial activity of manuka honey has been well documented (Molan,
      1992a,b,c, 1997) [Molan, P.C., 1992. The antibacterial activity of honey. 1: the
      nature of the antibacterial activity. Bee World 73 (1) 5-28; Molan, P.C., 1992.
      The antibacterial activity of honey. 2: variation in the potency of the
      antibacterial activity. Bee World 73 (2) 59-76; Molan, P.C., 1992. Medicinal uses
      for honey. Beekeepers Quarterly 26; Molan, P.C., 1997. Finding New Zealand honeys
      with outstanding antibacterial and antifungal activity. New Zealand Beekeeper 4
      (10) 20-26]. The current bioassays for determining this antimicrobial effect
      employ a well diffusion (Ahn and Stiles, 1990) [Ahn, C., Stiles, M.E., 1990.
      Antibacterial activity of lactic acid bacteria isolated from vacuum-packed meats.
      Journal of Applied Bacteriology 69, 302-310], (Weston et al., 1999) [Weston,
      R.J., Mitchell, K.R., Allen, K.L., 1999. Antibacterial phenolic components of New
      Zealand manuka honey. J. Food Chem. 64, 295-301] or disc diffusion (Taormina et
      al., 2001) [Taormina, Peter J., Niemira, Brendan A., Beuchat, Larry R., 2001.
      Inhibitory activity of honey against food borne pathogens as influenced by the
      presence of hydrogen peroxide and level of antioxidant power. Int. J. Food
      Microbiol. 69, 217-225] assay using zones of inhibition as indicators of
      bacterial susceptibility. The development of a 24-h spectrophotometric assay
      employing 96-well microtiter plates, that is more sensitive and more amenable to
      statistical analysis than the assays currently employed, was undertaken. This
      simple and rapid assay permits extensive kinetic studies even in the presence of
      low honey concentrations, and is capable of detecting inhibitory levels below
      those recorded for well or disc diffusion assays. In this paper, we compare the
      assay to both well and disc diffusion assays. The results we obtained for the
      spectrophotometric method MIC values show that this method has greater
      sensitivity than the standard well and disc diffusion assays. In addition, inter-
      and intra-assay variance for this method was investigated, demonstrating the
      methods reproducibility and repeatability.

PMID- 15979746
TI  - Automated methods for multiplexed pathogen detection.
AB  - Detection of pathogenic microorganisms in environmental samples is a difficult
      process. Concentration of the organisms of interest also co-concentrates
      inhibitors of many end-point detection methods, notably, nucleic acid methods. In
      addition, sensitive, highly multiplexed pathogen detection continues to be
      problematic. The primary function of the BEADS (Biodetection Enabling Analyte
      Delivery System) platform is the automated concentration and purification of
      target analytes from interfering substances, often present in these samples, via
      a renewable surface column. In one version of BEADS, automated immunomagnetic
      separation (IMS) is used to separate cells from their samples. Captured cells are
      transferred to a flow-through thermal cycler where PCR, using labeled primers, is
      performed. PCR products are then detected by hybridization to a DNA suspension
      array. In another version of BEADS, cell lysis is performed, and community RNA is
      purified and directly labeled. Multiplexed detection is accomplished by direct
      hybridization of the RNA to a planar microarray. The integrated IMS/PCR version
      of BEADS can successfully purify and amplify 10 E. coli O157:H7 cells from river
      water samples. Multiplexed PCR assays for the simultaneous detection of E. coli
      O157:H7, Salmonella, and Shigella on bead suspension arrays was demonstrated for
      the detection of as few as 100 cells for each organism. Results for the RNA
      version of BEADS are also showing promising results. Automation yields highly
      purified RNA, suitable for multiplexed detection on microarrays, with microarray
      detection specificity equivalent to PCR. Both versions of the BEADS platform show
      great promise for automated pathogen detection from environmental samples. Highly
      multiplexed pathogen detection using PCR continues to be problematic, but may be
      required for trace detection in large volume samples. The RNA approach solves the
      issues of highly multiplexed PCR and provides "live vs. dead" capabilities.
      However, sensitivity of the method will need to be improved for RNA analysis to
      replace PCR.

PMID- 15979747
TI  - An improved, real-time PCR assay for the detection of GC-rich and low abundance
      templates of Mycobacterium tuberculosis.
AB  - The detection of low abundance mRNA and/or GC-rich targets is very difficult
      using real-time PCR, often requiring laborious optimization procedures. This work
      shows that formamide is a useful PCR additive, increasing the sensitivity and
      specificity of SYBR Green real-time PCR to detect low abundance mycobacterial RNA
      from infected samples.

PMID- 15979748
TI  - Changes of viability and composition of the Escherichia coli flora in faecal
      samples during long time storage.
AB  - Long-time storage of faecal samples is necessary for investigations of intestinal
      microfloras. The aim of the present study was to evaluate how the viability and
      the composition of the Escherichia coli flora are affected in faecal samples
      during different storage conditions. Four fresh faecal samples (two from calves
      and two from infants) were divided into sub-samples and stored in four different
      ways: with and without addition of glycerol broth at -20 degrees C and at -70
      degrees C. The viability and the phenotypic diversity of the E. coli flora in the
      sub-samples were evaluated after repeated thawings and after storage during 1
      year. The samples stored for 1 year without thawing were also kept at room
      temperature for 5 days and subsequently analysed. According to phenotyping (PhP
      analysis) of 32 isolates per sample on day 0, all four samples contained two
      dominating strains of E. coli each, and between one and eight less common
      strains. Samples that were stored at -70 degrees C in glycerol broth showed equal
      or even higher bacterial numbers as the original samples, even after repeated
      thawings, whereas samples stored at -20 degrees C showed a considerably lower
      survival rate, also with addition of glycerol. Sub-samples containing glycerol
      broth that were kept at room temperature after storage for 1 year showed a clear
      increase in the number of viable cells as well as in diversity. The diversities
      in each sub-sample showed a tendency to decrease after several thawings as well
      as after storage. Generally, the E. coli populations in samples stored at -20
      degrees C were less similar to the population of the original sample than that in
      samples stored at -70 degrees C. Samples that had been mixed with glycerol broth
      had an E. coli flora more similar to that in the original sample than those
      without glycerol broth. Furthermore, the sub-samples that were kept at room
      temperature after storage for 1 year generally were more similar to the original
      samples than if they were processed directly. We conclude that for long time
      storage of faecal samples, storage at -70 degrees C is preferable. If samples
      have to be thawed repeatedly, addition of glycerol is preferable both for samples
      stored at -70 degrees C and for samples stored at -20 degrees C. Our data also
      have indicated that when E. coli isolates from faecal samples are selected for,
      e.g. analysis of virulence factors, it is necessary to pick several isolates per
      sample in order to obtain at least one isolate representing the dominating
      strain(s).

PMID- 15979749
TI  - Effects of varied pH, growth rate and temperature using controlled fermentation
      and batch culture on matrix assisted laser desorption/ionization whole cell
      protein fingerprints.
AB  - Rapid identification of microorganisms using matrix assisted laser
      desorption/ionization (MALDI) is a rapidly growing area of research due to the
      minimal sample preparation, speed of analysis and broad applicability of the
      technique. This approach relies on expressed biochemical markers, often proteins,
      to identify microorganisms. Therefore, variations in culture conditions that
      affect protein expression may limit the ability of MALDI-MS to correctly identify
      an organism. We have expanded our efforts to investigate the effects of culture
      conditions on MALDI-MS signatures to specifically examine the effects of pH,
      growth rate and temperature. Continuous cultures maintained in bioreactors were
      used to maintain specific growth rates and pH for E. coli HB 101. Despite
      measurable morphological differences between growth conditions, the MALDI-MS data
      associated each culture with the appropriate library entry (E. coli HB 101
      generated using batch culture on a LB media), independent of pH or growth rate.
      The lone exception was for a biofilm sample collected from one of the reactors
      which had no appreciable degree of association with the correct library entry.
      Within the data set for planktonic organisms, variations in growth rate created
      the largest variation between fingerprints. The effect of varying growth
      temperature on Y. enterocolitica was also examined. While the anticipated effects
      on phenotype were observed, the MALDI-MS technique provided the proper
      identification.

PMID- 15979750
TI  - Advancing vascular tissue engineering: the role of stem cell technology.
AB  - Atherosclerosis and heart disease are still the leading causes of morbidity and
      mortality worldwide. The lack of suitable autologous grafts has produced a need
      for artificial grafts but the patency of such grafts is limited compared to
      natural materials. Tissue engineering, whereby living tissue replacements can be
      constructed, has emerged as a solution to some of these difficulties. This, in
      turn, is limited by the availability of suitable cells from which to construct
      the vessels. The development of prosthesis using progenitor cells and switching
      these into endothelial cells is an important and exciting advance in the field of
      tissue engineering. Here, we describe recent developments in the use of stem
      cells for the development of replacement vessels. These paradigm shifts in
      vascular engineering now offer a new route for effective clinical therapy.

PMID- 15979751
TI  - The neurophysiology of attention-deficit/hyperactivity disorder.
AB  - Recent reviews of the neurobiology of Attention-Deficit/Hyperactivity Disorder
      (AD/HD) have concluded that there is no single pathophysiological profile
      underlying this disorder. Certainly, dysfunctions in the frontal/subcortical
      pathways that control attention and motor behavior are implicated. However, no
      diagnostic criteria or behavioral/neuroimaging techniques allow a clear
      discrimination among subtypes within this disorder, especially when problems with
      learning are also considered. Two major Quantitative EEG (QEEG) subtypes have
      been found to characterize AD/HD. Here we review the major findings in the
      neurophysiology of AD/HD, focusing on QEEG, and briefly present our previous
      findings using a source localization technique called Variable Resolution
      Electromagnetic Tomography (VARETA). These two techniques represent a possible
      objective method to identify specific patterns corresponding to EEG-defined
      subtypes of AD/HD. We then propose a model representing the distribution of the
      neural generators in these two major AD/HD subtypes, localized within basal
      ganglia and right anterior cortical regions, and hippocampal, para-hippocampal
      and temporal cortical regions, respectively. A comprehensive review of
      neurochemical, genetic, neuroimaging, pharmacological and neuropsychological
      evidence in support of this model is then presented. These results indicate the
      value of the neurophysiological model of AD/HD and support the involvement of
      different neuroanatomical systems, particularly the dopaminergic pathways.

PMID- 15979752
TI  - Control of Alicyclobacillus acidoterrestris in fruit juices by enterocin AS-48.
AB  - Alicyclobacillus acidoterrestris is a spoilage-causing bacterium in fruit juices.
      Control of this bacterium by enterocin AS-48 from Enterococcus faecalis A-48-32
      is described. Enterocin AS-48 was active against one A. acidocaldarius and three
      strains of A. acidoterrestris tested. In natural orange and apple juices
      incubated at 37 degrees C, vegetative cells of A. acidoterrestris DSMZ 2,498 were
      inactivated by enterocin AS-48 (2.5 microg/ml) and no growth was observed in 14
      days. In commercial fruit juices added of AS-48 (2.5 microg/ml) and inoculated
      with vegetative cells or with endospores of strain DSMZ 2,498, no viable cells
      were detected during 90 days of incubation at temperatures of 37 degrees C, 15
      degrees C or 4 degrees C, except for apple, peach and grapefruit juices
      inoculated with vegetative cells and incubated at 37 degrees C which were
      protected efficiently for up to 60 days. Remarkably, in all commercial fruit
      juices tested, no viable cells were detected as early as 15 min after incubation
      with the bacteriocin. Endospores incubated for a very short time (1 min) with
      increasing bacteriocin concentrations were inactivated by 2.5 microg/ml AS-48.
      Electron microscopy examination of vegetative cells and endospores treated with
      enterocin AS-48 revealed substantial cell damage and bacterial lysis as well as
      disorganization of endospore structure.

PMID- 15979753
TI  - Effect of inoculation of Carnobacterium divergens V41, a bio-preservative strain
      against Listeria monocytogenes risk, on the microbiological, chemical and sensory
      quality of cold-smoked salmon.
AB  - The aim of this study was to develop a bio-preservation strategy for cold-smoked
      salmon (CSS) by the use of lactic acid bacteria previously selected for their
      capability to inhibit the growth of Listeria monocytogenes in the product. The
      spoiling potential of three Carnobacterium strains (Carnobacterium divergens V41,
      Carnobacterium piscicola V1 and SF668) was tested in sterile CSS blocks
      inoculated by 10(4-5) CFU g(-)(1) and stored under vacuum for 9 days at 4 degrees
      C followed by 19 days at 8 degrees C. C. divergens V41 grew a little faster than
      the other strains and none of the three carnobacteria showed any adverse effect
      on quality of the product, i.e. no off-odour detected by a trained panel, no
      total volatile basic nitrogen (TVBN) production, no acidification and no biogenic
      amine except a slight production of tyramine. An application on commercial CSS
      was tested by spraying C. divergens V41 (10(4-5) CFU g(-1)) on slices of four
      batches freshly processed in different smoke-houses. Microbial, chemical and
      sensory characteristics were weekly compared to a control during 4 weeks of
      vacuum storage. When the natural microflora was initially weak (two batches<20
      CFU g(-1)), C. divergens V41 quickly reached 10(7-8) CFU g(-1) and a slight
      inhibition of endogenous Enterobacteriaceae, lactobacilli and yeasts was
      observed. The presence of C. divergens V41 was slightly detected (odour and
      flavour) but none of the sample was considered as spoiled by the sensory panel.
      When the natural microflora was initially high (2 batches>10(4-5) CFU g(-1)), no
      effect on the microflora, TVBN and biogenic amine production, nor on the sensory
      characteristics was observed in presence of C. divergens V41. In conclusion, bio
      preservation of CSS using lactic acid bacteria such as C. divergens V41 is a
      promising way to inhibit the growth of pathogenic bacteria such as L.
      monocytogenes with low effect on the quality of the product.

PMID- 15979755
TI  - Specific production rate of VHH antibody fragments by Saccharomyces cerevisiae is
      correlated with growth rate, independent of nutrient limitation.
AB  - Saccharomyces cerevisiae carrying a multicopy integrated expression vector
      containing the gene encoding a Llama antibody fragment, has been cultivated in
      continuous cultures both under carbon and nitrogen limiting conditions with
      galactose as the sole carbon source. VHH-R2 expression was under control of the
      inducible GAL7 promoter. Induction however, was independent of the galactose
      consumption rate and maximal at all growth rates. VHH-R2 was secreted with 70%
      efficiency at all growth rates and under both limitations. The specific
      production rate increased linear with increasing growth rate in a growth
      associated manner. However, when grown under nitrogen limitation at growth rates
      above 0.09 h(-1), the extracellular VHH-R2 was less active or part of the VHH-R2
      was in an inactive form. From our results we conclude that to obtain a maximal
      amount of VHH per kilogram biomass per hour, VHH production should be done in
      carbon limited continuous cultures at high specific growth rates.

PMID- 15979756
TI  - Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes
      containing bile salts.
AB  - PURPOSE: The feasibility of using proliposomes containing salmon calcitonin (sCT)
      and absorption enhancing agents, as an oral delivery system, to improve the
      intestinal absorption of sCT was explored using rats and Caco-2 cell systems.
      METHODS: Seventeen surfactants were examined for their effects with reference to
      accelerating the permeability of sCT (300 microg/ml) across Caco-2 cell
      monolayers, and damage to the intestinal epithelial cells, as measured by the
      change in transepithelial electrical resistance (TEER) across the cell monolayer.
      Proliposomes containing sCT (0.75%, w/w) and sodium taurodeoxycholate (NaTDC,
      2.5%, w/w) (TDC proliposomes) were prepared according to the standard method
      using sorbitol and phosphatidylcholine as core and wall-forming materials,
      respectively, administered intra-duodenally to rats, and plasma concentrations of
      sCT were subsequently determined by LC-MS. RESULTS: Among the surfactants
      examined, some bile salts including NaTDC appeared to be the most advantageous
      when estimated based on the balance between the permeation enhancement (e.g., a
      10.8-fold increase in the permeability of sCT for 0.1% NaTDC) and damage to the
      cells (e.g., a 3.55-fold decrease in the TEER value for 0.1% NaTDC). The
      administration of TDC proliposomes resulted in a 7.1-fold increase in the
      bioavailability (i.e., 0.49%) of sCT, when administered duodenally to rats. The
      size of the reconstituted liposomes in water was significantly smaller (e.g.,
      23.2 nm, number weighted diameter), and the entrapment efficiency (EE) of sCT in
      the reconstituted liposomes was 2.8-fold larger (54.9%), for TDC proliposomes,
      compared to proliposomes prepared without NaTDC (sCT proliposomes). CONCLUSION: A
      7.1-fold increase in the bioavailability of sCT could be achieved from the TDC
      proliposomes. In addition to the intrinsic activity of the bile salt to fluidize
      the membrane, the simultaneous delivery of sCT and NaTDC to the site of
      absorption in the intestine via proliposomes and the subsequent formation of
      lipophilic ion-pair complexes between sCT and NaTDC at the site might have been
      contributing factors in this outstanding absorption enhancement.

PMID- 15979757
TI  - An automated procedure to properly handle digital images in large scale tissue
      microarray experiments.
AB  - Tissue Microarray (TMA) methodology has been recently developed to enable "genome
      scale" molecular pathology studies. To enable high-throughput screening of TMAs
      automation is mandatory, both to speed up the process and to improve data
      quality. In particular, in acquiring digital images of single tissues (core
      sections) a crucial step is the correct recognition of each tissue position in
      the array. In fact, further reliable data analysis is based on the exact
      assignment of each tissue to the corresponding tumor. As most of the times tissue
      alignment in the microarray grid is far from being perfect, simple strategies to
      perform proper acquisition do not fit well. The present paper describes a new
      solution to automatically perform grid location assignment. We developed an ad
      hoc image processing procedure and a robust algorithm for object recognition.
      Algorithm accuracy tests and assessment of working constraints are discussed. Our
      approach speeds up TMA data collection and enables large scale investigation.

PMID- 15979758
TI  - Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles:
      what do point mutations achieve?
AB  - We report long time scale simulations of the 18-residue helical antimicrobial
      peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS
      micelles. The SDS micelle serves as an economical and effective model for a
      cellular membrane. Ovispirin, which is initially placed along a micelle diameter,
      diffuses out to the water-SDS interface and stabilizes to an interface-bound
      steady state in 16.35 ns of simulation. The final conformation, orientation, and
      the structure of ovispirin are in good agreement with the experimentally observed
      properties of the peptide in presence of lipid bilayers. The simulation succeeds
      in capturing subtle differences of the membrane-bound peptide structure as
      predicted by solid state NMR. The novispirins also undergo identical diffusion
      patterns and similar final conformations. Although the final interface-bound
      states are similar, the simulations illuminate the structural and binding
      properties of the mutant peptides which make them less toxic compared to
      ovispirin. Based on previous data and the current simulations, we propose that
      introduction of a bend/hinge at the center of helical antimicrobial peptides
      (containing a specific C-terminal motif), without disrupting the helicity of the
      peptides might attenuate host-cell toxicity as well as improve membrane binding
      properties to bacterial cellular envelopes.

PMID- 15979759
TI  - Regulation of thermogenesis by the central melanocortin system.
AB  - Adaptive thermogenesis represents one of the important homeostatic mechanisms by
      which the body maintains appropriate levels of stored energy and its core
      temperature. Dysregulation of adaptive thermogenesis promotes obesity. The
      central melanocortin system, in particular the melanocortin 4 receptor (MC4R)
      signaling pathway, influences the regulation of every aspect of energy balance,
      including thermogenesis, and plays a critical role in energy homeostasis in both
      rodent and man. This review will outline our current understanding of adaptive
      thermogenesis, focusing on the role of the central melanocortin pathway in the
      regulation of thermogenesis.

PMID- 15979760
TI  - Determination of the site of action of calcitonin gene-related peptide in the
      alteration of intracellular calcium levels in adult and neonatal rodent myocytes.
AB  - The purpose of this study is to elucidate the mechanism of action and site of
      action of calcitonin gene-related peptide (CGRP) and its effects on calcium
      concentrations in two types of cardiomyocytes, neonatal and adult, by employing
      real-time fluorescence imaging. CGRP caused an increase in intramyocytic calcium
      with adult cells, but a decrease with neonates. Treatment of adult myocytes with
      ouabain and ryanodine yielded results suggesting that CGRP action is not at the
      ryanodine receptor (RyR) and does not involve Na+ +K+ ATPase. Furthermore, in
      neonatal cardiomyocytes CGRP caused a reduction in intramyocytic calcium levels,
      and challenges with ryanodine and ouabain gave results supporting the hypothesis
      that CGRP acts at the sarcolemmal L-type calcium channel. Employing real-time
      fluorescence measurements in cultured, dedifferentiated adult cardiomyocytes,
      which are known to express a fetal phenotype and exhibit neonatal-like calcium
      transients, our acquisitions demonstrated a major reduction in intracellular
      calcium levels. Finally, our collaborative studies in human myocardium using
      fluorescence deconvolution microscopy revealed that CGRP localization was found
      in a pattern similar to that of the sarcolemmal L-type calcium channel.

PMID- 15979761
TI  - Recombinant prohormone convertase 1 and 2 cleave purified pro cholecystokinin
      (CCK) and a synthetic peptide containing CCK 8 Gly Arg Arg and the carboxyl
      terminal flanking peptide.
AB  - Purified recombinant prohormone convertase 1 and 2 (PC1 and PC2) cleave a peptide
      containing cholecystokinin (CCK) 8 Gly Arg Arg and the carboxyl-terminal peptide
      liberating CCK 8 Gly Arg Arg. PC1 and PC2 also cleave purified pro CCK,
      liberating the amino terminal pro-peptide while no carboxyl-terminal cleavage was
      detected. Under the conditions of the in vitro cleavage assay, it appears that
      the carboxyl-terminal cleavage site of pro CCK is not accessible to the enzymes
      while this site is readily cleaved in a synthetic peptide. Additional cellular
      proteins that unfold the prohormone may be required to expose the carboxyl
      terminal site for cleavage.

PMID- 15979762
TI  - Discovery of an MIT-like atracotoxin family: spider venom peptides that share
      sequence homology but not pharmacological properties with AVIT family proteins.
AB  - This project identified a novel family of six 66-68 residue peptides from the
      venom of two Australian funnel-web spiders, Hadronyche sp. 20 and H. infensa:
      Orchid Beach (Hexathelidae: Atracinae), that appear to undergo N- and/or C
      terminal post-translational modifications and conform to an ancestral protein
      fold. These peptides all show significant amino acid sequence homology to
      atracotoxin-Hvf17 (ACTX-Hvf17), a non-toxic peptide isolated from the venom of H.
      versuta, and a variety of AVIT family proteins including mamba intestinal toxin 1
      (MIT1) and its mammalian and piscine orthologs prokineticin 1 (PK1) and
      prokineticin 2 (PK2). These AVIT family proteins target prokineticin receptors
      involved in the sensitization of nociceptors and gastrointestinal smooth muscle
      activation. Given their sequence homology to MIT1, we have named these spider
      venom peptides the MIT-like atracotoxin (ACTX) family. Using isolated rat stomach
      fundus or guinea-pig ileum organ bath preparations we have shown that the
      prototypical ACTX-Hvf17, at concentrations up to 1muM, did not stimulate smooth
      muscle contractility, nor did it inhibit contractions induced by human PK1
      (hPK1). The peptide also lacked activity on other isolated smooth muscle
      preparations including rat aorta. Furthermore, a FLIPR Ca2+ flux assay using
      HEK293 cells expressing prokineticin receptors showed that ACTX-Hvf17 fails to
      activate or block hPK1 or hPK2 receptors. Therefore, while the MIT-like ACTX
      family appears to adopt the ancestral disulfide-directed beta-hairpin protein
      fold of MIT1, a motif believed to be shared by other AVIT family peptides,
      variations in the amino acid sequence and surface charge result in a loss of
      activity on prokineticin receptors.

PMID- 15979763
TI  - Evidence for direct actions of melanocortin peptides on bone metabolism.
AB  - Expression of melanocortin-4 receptor (MC4R) mRNA in developing rat limb buds,
      teeth, and skull bone first indicated a possible role for MC4R in bone
      metabolism. We therefore investigated whether MC4R mRNA was expressed in the rat
      osteosarcoma UMR106.06 cell line and in primary rat osteoblast cells. Reverse
      transcriptase-polymerase chain reaction (RT-PCR), Northern blot analysis, and
      ribonuclease protection assay (RPA) were used to demonstrate MC4R mRNA expression
      in UMR106.06 and primary osteoblast cells. MC4R mRNA was found to be localized to
      the periosteum of mouse bone using in situ hybridization. We also used RT-PCR and
      rat specific MC2R and MC5R oligonucleotides to amplify the correct size DNA
      fragments for these melanocortin receptors from rat primary osteoblasts. In
      conclusion, melanocortin receptor expression in mouse periosteum and rat
      osteoblasts suggests a direct role for POMC derived peptides in bone development
      and bone metabolism.

PMID- 15979764
TI  - New transport assay demonstrates vesicular acetylcholine transporter has many
      alternative substrates.
AB  - The acetylcholine-binding site in vesicular acetylcholine transporter faces
      predominantly toward the outside of the vesicle when resting but predominantly
      toward the inside when transporting. Transport-related reorientation is detected
      by an ATP-induced decrease in the ability of saturating substrate to displace
      allosterically bound [(3)H]vesamicol. The assay was used here to determine
      whether structurally diverse compounds are transported by rat VAChT expressed in
      PC12(A123.7) cells. Competition by ethidium, tetraphenylphosphonium and other
      monovalent organic cations with [(3)H]vesamicol is decreased when ATP is added,
      and the effect depends on proton-motive force. The results indicate that many
      organic molecules carrying +1 charge are transported, even though the compounds
      do not resemble acetylcholine in structural details.

PMID- 15979765
TI  - Quantification of oxidized RNAs in Alzheimer's disease.
AB  - Cytoplasmic RNA oxidation is a prominent feature of vulnerable neurons in the
      brains of Alzheimer's disease (AD) patients. We previously demonstrated that
      messenger RNAs (mRNA) are oxidized in AD brains. However, the magnitude of the
      mRNA oxidation is unclear. In the present study, we separated oxidized mRNAs from
      non-oxidized mRNAs by immunoprecipitation and then quantitatively analyzed both
      mRNA fractions. Surprisingly, 30-70% of the mRNAs isolated from AD frontal
      cortices were oxidized while the abundance of oxidized mRNAs was low in age
      matched normal controls. Furthermore, we previously showed that some mRNA species
      are more susceptible to oxidative damage. Here, we quantified the degree of
      oxidation for individual mRNA species that were previously found to be oxidized
      in AD. Quantitative analysis revealed that the relative amounts of oxidized
      transcripts reach 50-70% for some mRNA species. These high abundances implicate
      the potential contribution of mRNA oxidation to the pathogenesis of AD.

PMID- 15979766
TI  - Synthesis and antimalarial activities of some furoxan sulfones and related
      furazans.
AB  - Furoxan derivatives bearing a sulfone moiety at position 3 or 4 were synthesized
      and tested for their antimalarial action on the chloroquine-sensitive D10 and the
      chloroquine-resistant W2 strains of Plasmodium falciparum. The furazan analogues
      were considered for comparison. The most active compounds were the products in
      which the -SO2R groups are at the 3-position of the furoxan system. These latter
      substances displayed an antimalarial activity in the microM range, possibly
      related in part to their ability to release NO.

PMID- 15979767
TI  - Synthesis, characterization and antimicrobial activity of some substituted 1,2,3
      triazoles.
AB  - Two substituted 1,2,3-triazoles 4 and 6 have been synthesized by the 1,3-dipolar
      cycloaddition reaction of 4-azido-8-(trifluoromethyl)quinoline 2 with ethyl
      acetoacetate and acetylacetone, respectively. The reaction of 2 with ethyl
      acetoacetate afforded 1-[8-(trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3
      triazole-4-carboxylic acid 3 and with acetylacetone afforded 1-{1-[8
      (trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazol-4-yl}ethanone 5.
      Compound 3 is converted into its corresponding acid hydrazide and then condensed
      with different aromatic aldehydes to yield Schiff's base, N-[1-arylmethylene]-1
      [8-(trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazole-4-carbohydrazides
      4. Compound 5 is condensed with aromatic aldehydes to obtain [1-aryl-4-{1-[8
      (trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazol-4-yl}prop-2-en-1-ones
      6. The newly prepared 1,2,3-triazole derivatives 4 and 6 have been characterized
      by IR, NMR and mass spectral data. These compounds were screened for their
      antimicrobial activity.

PMID- 15979768
TI  - Effect of "preoperative" oral carbohydrate treatment on insulin action--a
      randomised cross-over unblinded study in healthy subjects.
AB  - BACKGROUND AND AIMS: Preoperative intake of a clear carbohydrate-rich drink
      reduces insulin resistance after surgery. In this study, we evaluated whether
      this could be related to increased insulin sensitivity at the onset of surgery.
      Furthermore, we aimed to establish the optimal dose-regimen. METHODS: Six healthy
      volunteers underwent hyperinsulinaemic (0.8 mU/kg/min), normoglycaemic (4.5
      mmol/l) clamps and indirect calorimetry on four occasions in a crossover
      randomised order; after overnight fasting (CC), after a single evening dose (800
      ml) of the drink (LC), after a single morning dose (400 ml, CL) and after intake
      of the drink in the evening and in the morning before the clamp (LL). Data are
      presented as mean+/-SD. Statistical analysis was performed using the Student's t
      test and ANOVA. RESULTS: Insulin sensitivity was higher in CL and LL (9.2+/-1.5
      and 9.3+/-1.9 mg/kg/min, respectively) compared to CC and LC (6.1+/-1.6 and 6.6+/
      1.9 mg/kg/min, P<0.01 vs. CL and LL). CONCLUSIONS: A carbohydrate-rich drink
      enhances insulin action 3 h later by approximately 50%. Enhanced insulin action
      to normal postprandial day-time level at the time of onset of anaesthesia or
      surgery is likely to, at least partly, explain the effects on postoperative
      insulin resistance.

PMID- 15979769
TI  - Financial requirements of immunisation programmes in developing countries: a 2004
      2014 perspective.
AB  - Vaccines are a key contributor to public health, especially in developing
      countries. Despite numerous demonstrations of the cost-effectiveness of
      immunisation, vaccines spending accounted for only 1.7% of the total
      pharmaceutical market in 2002, when UNICEF estimated that 34 million children
      were not reached by routine immunisation, most of them in developing countries.
      Several international organizations or initiatives, like the Global Alliance for
      Vaccines and Immunisation (GAVI), have defined a long-term goal of universal
      immunisation in developing countries. There is an urgent need to estimate the
      financial resources required to meet this goal. The objective of this study was
      to anticipate the funding needs for childhood immunisation in developing
      countries over the 2004-2014 period. The study scope includes all the 75
      countries eligible for support from GAVI, and covers existing vaccines that are
      considered as a priority for GAVI (DTP (diphtheria, tetanus, pertussis),
      hepatitis B, Haemophilus influenzae type b (as a stand alone presentation or in
      combination with DTP) and yellow fever) as well as future vaccines (meningitis A
      and C, rotavirus, human papilloma virus (HPV), malaria, Streptococcus pneumoniae
      and tuberculosis) likely to be available within the 10-year period. We developed
      a methodology to estimate the number of doses required, based on disease
      prevalence and incidence, target populations, introduction dates of new vaccines,
      coverage dynamics and dosing regimen. The introduction price and price evolution
      of vaccines over time were modelled, taking into account the type of vaccine, the
      expected return on investment from vaccine manufacturers and the competitive
      landscape. Non-vaccine costs (capital costs and non-vaccine recurrent costs) were
      estimated based on the number of people immunised and number of doses dispensed,
      using available case studies as a reference. According to the optimal scenario
      that would consider the provision of all vaccines to all relevant developing
      countries as soon as they are available, funding requirements to cover the
      associated total costs over the 10-year period were estimated to be about US$ 30
      billion. Vaccines-related costs represent the largest share, with estimated costs
      of US$ 21 billion (among which 18 billion for new vaccines), the remaining needs
      being split between capital costs and other recurrent costs. Accounting for the
      main imponderables (such as delay in vaccines launch compared to industry plans)
      as well as probable phasing of vaccine introduction in countries, the total costs
      of immunisation would be reduced to US$ 14-17 billion over the same period.
      Vaccines-related costs represent the largest share (US$ 7.1-9.3 billion, among
      which 4.3-6.5 billion for new vaccines). This study advocates for the
      anticipation of the substantial financial resources needed to (a) purchase and
      introduce these vaccines in the developing countries in order to reduce the time
      lag between availability in industrialised and developing countries; and (b)
      stimulate vaccine researchers and manufacturers to continue research and
      development of much needed vaccines for the developing world.

PMID- 15979770
TI  - Development of recombinant VP2 vaccine for the prevention of infectious bursal
      disease of chickens.
AB  - The objective of the present study was to investigate the feasibility of a
      subunit vaccine and a live bacteria vaccine to protect chickens against
      infectious bursal disease virus (IBDV) infection. The gene for VP2 of a new wild
      type very virulent IBDV (vvIBDV) strain was cloned into an Escherichia coli
      expression system. Following expression, the recombinant VP2 and the induced
      expression bacteria were used to vaccinate chickens against virulent IBDV
      (vIBDV). Three weeks after the vaccination, chickens were inoculated with IBDV
      strain BC 6/85 by intranasal route or eyedrop route, prior to challenge anti-IBDV
      serum antibody was detected by AGP. All chickens vaccinated with recombinant VP2
      could be detected anti-IBDV antibody. The subunit vaccine of recombinant VP2
      conferred protection for 90--100% chickens, live bacteria vaccine of recombinant
      VP2 conferred protection for 85.7% chickens. The results indicate that E. coli BL
      21/pET 28 a-VP2 could be used to develop recombinant VP2 vaccine against
      infectious bursal disease in chickens.

PMID- 15979771
TI  - Cognitive approaches to insomnia.
AB  - Cognition is a broad term that refers to all mental activities and encompasses
      attention, perception, memory, reasoning, beliefs, attributions and expectations.
      The aim of the present paper is to draw together the major research findings
      relating to the importance of cognition in insomnia. Although the research to
      date has tended to focus on the role of unwanted intrusive thought (also known as
      worry or cognitive arousal), there is evidence that a broad range of cognitive
      processes are important for a full understanding of insomnia. These include
      beliefs, attributions, expectations, perception and attention. The treatment
      implications of this evidence are discussed, as are priorities for future
      research.

PMID- 15979772
TI  - An alternative approach for the safety evaluation of new and existing chemicals,
      an exercise in integrated testing.
AB  - Various in vitro and in silico methods without animals were applied to 10
      substances listed on ELINCS with a complete VIIA base-set available at NOTOX. The
      hazard assessment for these substances was performed on basis of available non
      animal data, QSAR, PBBK-modelling and additional, new in vitro testing was
      applied. Based on these data predictions on fish toxicity, acute toxicity, skin-
      and eye-irritation, sensitisation, and toxicity after repeated dosing were made.
      The predictions were compared with the outcome of the in vivo tests. Nine out of
      ten predictions on fish LC(50) proved to be correct. For skin- and eye-irritation
      70% was predicted correctly. Sensitisation was predicted correctly for 7 out of
      10 substances, but three false negatives were found. Acute oral toxicity (LD(50))
      and repeated dose toxicity were less successful (5 out of 10 and 2 out of 10
      correct predictions, respectively); application of the PBBK model proved
      successful. Acute dermal toxicity was predicted correctly in 9 out of 10 cases.
      In general an over-estimation of systemic toxicity was found, which can be
      explained by an over-prediction of cytotoxicity and worst case assumptions on
      absorption and binding to (plasma) proteins. This integrated approach leads to a
      38% reduction of laboratory animals.

PMID- 15979773
TI  - "When the obvious brother is not there": political and cultural contexts of the
      orphan challenge in northern Uganda.
AB  - It is estimated that two million of Uganda's children today are orphaned
      primarily due to AIDS. While recognising the immense impact of HIV/AIDS on the
      present orphan problem, this article calls for a broader historic and cultural
      contextualisation to reach an understanding of the vastness of the orphan
      challenge. The study on which the article is based was carried out among the
      Langi in Lira District, northern Uganda, with a prime focus on the situation of
      orphans within the extended family system. The data were collected through
      ethnographic fieldwork (8 months); in-depth interviews with community leaders
      (21), heads of households (45) and orphans (35); through focus group discussions
      (5) with adult men and women caring for orphans, community leaders and with
      orphans; and also through documentary review. A survey was conducted in 402
      households. The findings reveal a transition over the past 30 years from a
      situation dominated by 'purposeful' voluntary exchange of non-orphaned children
      to one dominated by 'crisis fostering' of orphans. Sixty-three percent of the
      households caring for orphans were found to be no longer headed by resourceful
      paternal kin in a manner deemed culturally appropriate by the patrilineal Langi
      society, but rather by marginalised widows, grandmothers or other single women
      receiving little support from the paternal clan. This transition is partly linked
      to an abrupt discontinuation of the Langi 'widow inheritance' (laku) practice. It
      is argued that the consequential transformations in fostering practices in
      northern Uganda must be historically situated through a focus on the effects of
      armed conflicts and uprooting of the local pastoral and cotton-based economy,
      which have occurred since the late 1970s. These processes jointly produced
      dramatic economic marginalisation with highly disturbing consequences for orphans
      and their caretakers.

PMID- 15979774
TI  - Subchronic 4-month oral toxicity study of dried Smallanthus sonchifolius (yacon)
      roots as a diet supplement in rats.
AB  - Yacon roots are a rich source of fructooligosaccharides (FOS) and have a long use
      tradition as food in the Andean region. However, there are no published reports
      regarding their toxicology and use safety. The aim of this study was to analyze
      the effects of subchronic (4-months) oral consumption of dried yacon root flour
      as a diet supplement using normal Wistar rats. Two daily intake levels were used,
      equivalent to 340 mg and 6800 mgFOS/body weight, respectively. Yacon administered
      as a diet supplement was well tolerated and did not produce any negative
      response, toxicity or adverse nutritional effect at both intake levels used.
      Yacon root consumption showed no hypoglycemic activity in normal rats and
      resulted in significantly reduced post-prandial serum triacylglycerol levels in
      both doses assayed. Conversely, serum cholesterol reduction was not statistically
      significant. Cecal hypertrophy was observed in rats fed only the high dose. Our
      results indicating lack of toxicity and a certain beneficial metabolic activity
      in normal rats warrant further experiments with normal subjects and patients
      suffering metabolic disorders. They should also be considered when establishing
      the regulatory framework of this natural product by national health authorities
      and international trade agencies.

PMID- 15979775
TI  - Developmental toxicity study with diethylene glycol dosed by gavage to CD rats
      and CD-1 mice.
AB  - Diethylene glycol (DEG; CAS Number 111-46-6) is a widely used industrial liquid
      chemical with a potential for human exposure. In view of the established
      teratogenic effects caused by ethylene glycol in laboratory animals, the
      developmental toxicity of DEG was investigated in mice and rats, species known to
      be sensitive to the developmental toxicity of ethylene glycol. Timed-pregnant CD
      1 mice and CD rats were dosed daily by gavage with undiluted DEG over gestational
      days (gd) 6-15. Based on probe studies, mouse dosages were 0 (distilled water),
      559, 2795 and 11,180 mg/kg/day, and those for rats 0, 1118, 4472 and 8944
      mg/kg/day. They were examined daily for clinical signs of toxicity, and body
      weights, food consumption and water consumption measured periodically throughout
      gestation. At necropsy, on gd 18 (mice) or gd 21 (rats), dams were examined for
      gross pathology and body, gravid uterus, liver and kidney weights were measured.
      Maternal rat kidneys were examined histologically. Fetuses were weighed, sex
      determined, and examined for external, visceral and skeletal variations and
      malformations. With mice there was maternal toxicity at 11,180 mg/kg/day
      (mortality, signs, increased water consumption) and at 2795 mg/kg/day (increased
      water consumption). Implantations were comparable across all groups. Fetal body
      weights were significantly reduced at 11,180 mg/kg/day. There were no increases
      in variations or malformations, either total, by category, or individually. With
      rats, maternal toxicity was present at 8944 mg/kg/day (mortality, signs, reduced
      body weight gain, reduced food consumption, increased water consumption,
      increased liver weight, increased kidney weight, and renal histopathology), and
      4472 mg/kg/day (increased water consumption). There were no treatment-related
      effects on corpora lutea or implantations. Fetal body weights were reduced at
      8944 mg/kg/day. There were no significant effects with respect to total or
      individual external or visceral variations. Individual skeletal variations were
      significantly increased at 8944 mg/kg/day (poorly ossified interparietal, poorly
      ossified thoracic centra number 10 and number 13, and bilobed thoracic centrum
      number 10) and 4472 mg/kg/day (split anterior arch of atlas and bilobed thoracic
      centrum number 10). This pattern of delayed ossification is consistent with
      reduced fetal body weight. Malformations, total, by category, or individually,
      were similar between the control and DEG groups. Thus, under the conditions of
      these studies, the no-observed-effect-level (NOEL) for DEG given by gavage over
      gd 6-15 was 559 mg/kg/day with the mouse and 1118 mg/kg/day with the rat for
      maternal toxicity, and 2795 mg/kg/day with mice and 1118 mg/kg/day with rats for
      developmental toxicity (fetotoxicity). There were no indications of
      embryotoxicity or teratogenic effects at any dosage in either species.

PMID- 15979776
TI  - Reactivity of trypsin in reverse micelles: neglected role of aggregate size
      compared to water-pool components.
AB  - The catalytic efficiency of trypsin was estimated in cationic reverse micelles as
      a function of the concentration of water-pool components and aggregate size to
      determine their independent influence on enzyme activity. The variation in the
      aggregate size/water-pool size was achieved by changing both the W0 (mole ratio
      of water to surfactant) and the headgroup area of surfactant through introduction
      of hydroxyethyl groups at the polar head. The local molar concentrations of water
      present inside the water-pool ([H2O]wp) of different cationic reverse micelles
      across varying W0 was estimated using a modified phenyl cation-trapping protocol.
      The [H2O]wp in cationic reverse micelles (surfactant/isooctane/n-hexanol/water)
      increases with W0 and attains the molarity of normal water beyond W0=40
      irrespective of the nature of headgroup. Concurrently, the catalytic activity of
      trypsin compartmentalized within the water-pool increases with the increase in
      [H2O]wp upto an optimal W0=40 in organized solutions of any surfactant. The
      aggregate size (determined by static light scattering) also increases expectedly
      with W0 and noticeably with the area of the surfactant headgroup at similar W0.
      Since the enzyme activity rises both with the increase in water-pool size and
      [H2O]wp, trypsin's efficiency was compared with these two parameters across
      reverse micelles of varying surfactant headgroup size at similar W0 to determine
      their probable independent influence in regulating the enzyme activity.
      Noticeably, the efficiency of trypsin rises two to ninefold in spite of the
      [H2O]wp being distinctly lower in case of hydroxyethyl group substituted
      surfactants compared to cetyltrimethylammonium bromide w/o microemulsions at
      similar W0. Thus, the influence of the aggregate size possibly plays an important
      role alongwith the [H2O]wp in modulating the enzyme activity.

PMID- 15979777
TI  - Jaromir Baron von Mundy--founder of the Vienna ambulance service.

PMID- 15979779
TI  - Thermodynamic calculations in biological systems.
AB  - The ability to compute intra- and inter-molecular interactions provides the
      opportunity to gain a deeper understanding of previously intractable problems in
      biochemistry and biophysics. This review presents three examples in which
      molecular dynamics calculations were used to gain insight into the atomic detail
      underlying important experimental observations. The three examples are the
      following: (1) Entropic contribution to rate acceleration that results from
      conformational constraints imposed on the reactants; (2) Mechanism of force
      unfolding of a small protein molecule by the application of a force that
      separates its N- and C-terminals; and (3) Loss of translational entropy
      experienced by small molecules when they bind to proteins.

PMID- 15979778
TI  - Association between perceived social support and Th1 dominance.
AB  - Social support is supposed to have a positive health effect via alteration of
      immunity. In this study, associations between perceived social support and immune
      systems were examined. Immunological assessments, e.g. T cell count, Natural
      Killer cell count, Interferon-gamma, Interleukin-4, and psychological
      assessments, e.g. Generic Job Stress Questionnaire were conducted on male
      employees. Two-way (social support x job stressor) analyses of covariance
      controlling for age, smoking, alcohol consumption, and exercise revealed that
      there were main effects of perceived social support on NK cell counts, IL-4, and
      Th1/Th2 balance. On the other hand, interaction effects were observed on T cell
      counts and INF-gamma production in vitro. Social support affects immune function
      in a way that is consistent with both the direct and buffering hypotheses
      depending on the sources of support and the immune parameter.

PMID- 15979780
TI  - Comparative analysis of base biases around the stop codons in six eukaryotes.
AB  - Using full-length cDNA sequences, a comparative analysis of sequence patterns
      around the stop codons in six eukaryotes was performed. Here, it was showed that
      the codon immediately before and after the stop codons (defined as -1 codon and
      +1 codon, respectively) were much more biased than other examined positions,
      especially at the second position of -1 codons and the first position of +1
      codons which were rich in As/Us and purines, respectively, for most species. The
      author speculated that strongly biased sequence pattern from position -2 to +4
      might act as an extended translation termination signal. Translation termination
      was catalyzed by release factors that recognized the stop codons. The multiple
      amino acid sequence alignment of eukaryotic release factor 1 (eRF1) of 20 species
      showed that there were 16 residue sites that were strictly conserved, especially
      the invariant amino acids Ile70 and Lys71. Accordingly, it could be inferred that
      those candidate amino acids might involve in the recognition process. Moreover,
      the possible stop signal recognition hypothesis was also discussed herein.

PMID- 15979781
TI  - A p53 polymorphism modifies the risk of hepatocellular carcinoma among non
      carriers but not carriers of chronic hepatitis B virus infection.
AB  - To clarify the modifying effect of the codon 72 p53 polymorphism on
      hepatocellular carcinoma (HCC) stratified by chronic hepatitis B virus (HBV)
      infection status, 111 incident cases of HCC and 424 controls in HBV-negative
      subjects and 135 cases and 125 controls in HBV-positive subjects were identified.
      No correlation between the polymorphism and HCC risk was found when comparing the
      HBV-positive cases to controls. However, in HBV-negative subjects, Arg/Pro and
      Pro/Pro genotypes had a 1.97-fold and a 3.36-fold increased risk for HCC,
      respectively. In subjects with the Pro allele and family history of HCC yielded
      an 11.81-fold increased risk of HCC.

PMID- 15979782
TI  - Transcript quantification of Dresden G protein-coupled receptor (D-GPCR) in
      primary prostate cancer tissue pairs.
AB  - Recently, we identified the novel protein D-GPCR (Dresden G protein-coupled
      receptor) which is selectively overexpressed in human prostate cancer (PCa) and
      belongs to the subfamily of odorant-like orphan GPCRs. Quantification of D-GPCR
      transcripts in paired malignant and non-malignant prostate tissues of 106
      patients with primary PCa by real-time PCR demonstrated a significant up
      regulation of this gene in tumor samples. Furthermore, its expression increases
      with higher tumor stages and grades. The evaluation of D-GPCR expression as a
      potential molecular tumor marker was performed by receiver-operating
      characteristic curve (ROC) analysis resulting in an area under the curve (AUC)
      value of 0.6452. Hence, the evaluation of D-GPCR as possible additive diagnostic
      tool and putative therapy target appears promising.

PMID- 15979783
TI  - The emerging role of CD44 in regulating skeletal micrometastasis.
AB  - The hyaluronan (HA) receptor CD44 has a well documented role in tumour
      metastasis. This review focuses on the potential significance of CD44 expression
      and function in regulating the metastasis of both haematological malignancies and
      solid tumours to the bone. Specifically, the review will discuss the evidence
      that HA-CD44 interactions facilitate the arrest of circulating malignant cells
      upon the bone marrow endothelial cells and discuss data that suggests CD44 may
      orchestrate the ability of tumour cells to regulate the modification of the bone
      matrix and support its colonisation by malignant cells.

PMID- 15979784
TI  - Differential 14-3-3 sigma DNA methylation and expression in c-myc- and activated
      H-ras-transformed cells under r- and K-selection.
AB  - We cloned rat 14-3-3 sigma, a mediator of p53 tumor suppressor, as a target of K
      selection. 14-3-3 sigma expression is suppressed with DNA methylation in breast
      cancers while its overexpression with hypomethylation is frequent in pancreatic
      cancers. These opposite findings were recapitulated through r- and K-selection of
      transformed rat embryo fibroblasts. 14-3-3 sigma expression was suppressed with
      DNA methylation after r-selection and the gene was overexpressed and demethylated
      in K-selected cells. 5-aza-2'-deoxycytidine recovered 14-3-3 sigma expression in
      r-selected cells. The presence of heterogeneous methylation patterns and
      expression levels before selection suggests that different 14-3-3 sigma
      expression levels play a role as a prerequisite for selection and clonal
      evolution.

PMID- 15979785
TI  - The role of the multidrug resistance-associated protein 1 gene in neuroblastoma
      biology and clinical outcome.
AB  - Multidrug resistance is a major obstacle to cancer treatment and leads to poor
      prognosis for the patient. Multidrug resistance-associated protein 1 (MRP1) can
      confer drug resistance in vitro and MRP1 may play a role in the development of
      drug resistance in several cancers including acute myeloid leukaemia, small cell
      lung cancer, T-cell leukaemia and neuroblastoma. The majority of patients with
      neuroblastoma present with widely disseminated disease at diagnosis and despite
      intensive treatment, the prognosis for such patients is dismal. There is
      increasing evidence for the involvement of the MYCN oncogene, and its down-stream
      target, MRP1, in the development of multidrug resistance in neuroblastoma. Given
      the importance of MRP1 overexpression in neuroblastoma, MRP1 inhibition may be a
      clinically relevant approach to improving patient outcome in this disease.

PMID- 15979786
TI  - Establishment of process technology for the manufacture of dinitrogen pentoxide
      and its utility for the synthesis of most powerful explosive of today--CL-20.
AB  - This paper reviews the recent work done on the synthesis as well as
      characterization of dinitrogen pentoxide (DNPO). The physico-chemical
      characteristics of DNPO are also discussed. The review brings out the key aspects
      of N2O5 technology with relevance to realize modern and novel HEMs. The paper
      also includes the aspects related with establishing the synthesis facility of
      dinitrogen pentoxide at HEMRL by gas phase interaction of N2O4 with O3. The
      process parameters for the synthesis of N2O5 at 50 g/batch have been optimized.
      The synthesized dinitrogen pentoxide has been characterized by UV [204, 213, 258
      nm (pi-->pi*) 378 and 384 nm (n-->pi*)] and IR (1428, 1266, 1249, 1206, 1044,
      822, 750, 546 and 454 cm(-1)) spectroscopy. The DSC clearly showed the
      sublimation of N2O5 at 32 degrees C. The nitration studies on 2,6,8,12
      tetraacetylhexaaza tetracyclo[5,5,0,0(3,11)0(5,9)]dodecane (TAIW) proved its
      viability in 2,4,6,8,10,12-hexanitro-2,4,6,8(10,12))-hexaazatetracyclo
      [5,5,0,0(3,11)0(5,9)]dodecane (CL-20) synthesis. The synthesized CL-20 and its
      precursors have also been subjected to hyphenated TG-FTIR studies to understand
      decomposition pattern.

PMID- 15979787
TI  - Degradation of 4-chlorophenol by a microwave assisted photocatalysis method.
AB  - In this work, the degradation of 4-chlorophenol (4CP) under simultaneous
      microwave assisted UV (electrodeless discharge lamp) photocatalysis technique
      (MW/UV/TiO2) was investigated. Several factors affecting the degradation of 4CP
      by MW/UV/TiO2 method, such as the dosage of photocatalysts, the initial pH value
      of the solutions, gas bubbling, light intensity and addition of H2O2 oxidant,
      were studied in detail. The synergistic effects between microwave irradiation and
      TiO2 photocatalysis were also studied. The major intermediates were found to be
      chlorobenzene, phenol, hydroquinone, benzoquinone and 4-chlorocatechol. Based on
      the results, a general reaction pathway for the degradation of 4CP was proposed.

PMID- 15979788
TI  - Particle size distribution of polycyclic aromatic hydrocarbons in motorcycle
      exhaust emissions.
AB  - The size distribution of polycyclic aromatic hydrocarbons (PAHs) in emission of a
      two-stroke carburetor motorcycle was studied. The exhaust gas from the test
      motorcycle was passed to a dilution tunnel and collected using a 10 cascade micro
      orifice uniform deposit impactor (MOUDI) of 0.056-10 microm aerodynamic diameter
      fitted with aluminum substrates. All MOUDI substrates were analyzed for
      particulate mass and for PAHs by GC/MS. Most of the 21 analyzed PAHs have two
      significant modes that peak at <0.1 and 0.18-0.32 microm. For some PAHs, a third
      peak appears around 1.8 microm. MOUDI impactor samples show that 88.9%
      particulate and 89.6% PAH mass distributed smaller than 2.5 microm. Mass median
      diameters of PAHs are about 0.2 microm. Total benzo[a]pyrene toxic equivalency
      emission factor was 440+/-13.8 ng/km for the test motorcycle. An average of 90.3%
      of carcinogenicity is observed in particulate smaller than 1.0 microm. The
      results suggest that submicron particulates predominate in the exhaust from
      motorcycle and exhibit high carcinogenic potency for these particulate.

PMID- 15979789
TI  - The functional COMT polymorphism, Val 158 Met, is associated with logical memory
      and the personality trait intellect/imagination in a cohort of healthy 79 year
      olds.
AB  - A polymorphism (Val 158 Met) in the gene for catechol-O-methyl transferase (COMT)
      was previously associated with differences in cognitive ability and personality.
      Here we examine associations between this polymorphism and cognitive ability,
      cognitive aging, personality and mood in 460 relatively healthy people born in
      1921. All had cognitive ability measured at age 11 in the Scottish Mental Survey
      of 1932, and again at age 79. COMT genotype was not associated with childhood IQ.
      At age 79, COMT genotype was significantly related to differences in verbal
      declarative memory (scores on the Logical Memory test; p=0.028) and to scores on
      the personality trait of intellect/imagination (p=0.023), adjusted for sex and
      childhood IQ. In both cases the Val/Met heterozygotes had higher scores than both
      homozygous groups. There were trends toward the heterozygotes having higher
      scores on the personality traits of agreeableness and conscientiousness. The
      effect of COMT genotype on Logical Memory scores was independent of the effect of
      APOE genotype, and similar in effect size. Therefore, COMT genotype may
      contribute to differences in normal cognitive aging and to differences in some of
      the major personality traits in old age.

PMID- 15979790
TI  - Modulation of pain-induced endothelial dysfunction by hypnotisability.
AB  - Mental stress induces endothelial dysfunction, that is a reduction of the post
      occlusion brachial artery flow-mediated vasodilation (FMD). This does not occur
      in subjects highly susceptible to hypnosis (Highs) in either the waking or
      hypnotic state. The aim of the present experiment was to assess whether
      endothelial dysfunction is also induced by acute nociceptive stimulation and
      whether high hypnotisability and/or the specific instruction of analgesia prevent
      its occurrence in awake highly hypnotizable individuals. Thus, nine Highs and
      nine subjects with low susceptibility to hypnosis (Lows) underwent an
      experimental session including the administration of pressor pain and of pressor
      pain associated with the instruction of analgesia. Heart rate, basal artery
      diameters and brachial artery flow-mediated vasodilation were measured during
      stimulation and rest conditions. Heart rate exhibited slight changes not
      modulated by hypnotisability. During painful stimulation both Highs and Lows
      showed a decrease of FMD, but it was significantly less pronounced in Highs.
      During the administration of painful stimulation together with the instruction of
      analgesia, only Highs reported analgesia and their FMD no longer decreased. This
      study provides the first evidence of pain-related endothelial dysfunction and
      extends previous findings concerning a sort of natural protection of Highs
      against the vascular effects of mental stress to acute pain.

PMID- 15979791
TI  - Lack of sex differences in modulation of experimental intraoral pain by diffuse
      noxious inhibitory controls (DNIC).
AB  - The aims of this study were to investigate possible sex differences in (a)
      intraoral pain evoked by topical application of capsaicin to the gingiva, and (b)
      the modulation of this pain by diffuse noxious inhibitory controls (DNIC). Three
      groups with a total of fifty-four healthy volunteers (20 men, 20 women using oral
      contraceptives (W+OC), 14 women not using (W-OC)) completed the study. In two
      sessions, intraoral pain was evoked by topical application of 30microL 5%
      capsaicin to the gingiva. Conditioning stimuli were applied with three min hand
      immersion in ice water in one session and 30 degrees C water (control) in another
      session. The capsaicin-evoked pain and the water-evoked pain were evaluated by
      the participants on visual analogue scales (VAS). No main effects of group in
      capsaicin-evoked pain (P>0.062) or water-evoked pain (P>0.149) were found. There
      was a significant group x time interaction (P<0.001) with W+OC reporting lower
      capsaicin-evoked pain scores than W-OC in the early phase (2-3min) and lower pain
      scores than men in the later phase (5-11min). The degree of modulation by DNIC
      did not differ between groups (P=0.636). In conclusion, for a superficial type of
      intraoral pain, only minor sex differences were found in pain intensity and no
      differences in the degree of endogenous modulation by DNIC. Female sex and the
      use of OC may not consistently be associated with higher sensitivity to pain.

PMID- 15979792
TI  - Acute pain: individual patient meta-analysis shows the impact of different ways
      of analysing and presenting results.
AB  - Individual patient meta-analysis using information from clinically homogeneous
      acute pain trials with observations over 24h was used to investigate different
      ways trials can be analysed and reported. There were 13 third-molar extraction
      trials, with 1,330 patients using rofecoxib 50mg, 303 using ibuprofen 400mg, and
      570 using placebo. Pain relief scores were available at individual time points,
      plus time to remedication. Many more patients remedicated with placebo than
      ibuprofen 400mg, and more with ibuprofen than rofecoxib 50mg. Median time to
      remedication, the proportion remedicated at various times, or survival curves
      would be useful outcomes. In dealing with missing data points when patients
      remedicated, baseline observation carried forward was more conservative than last
      observation carried forward, resulting in higher (worse) NNTs and lower average
      pain scores after 12 and 24h. Results based on both methods might be sensible for
      trials longer than eight hours. The distribution of pain relief was highly
      skewed, especially at later times, when almost no patient was average. Different
      cut points for pain relief (at least 25, 50 or 75% maxTOTPAR) and longer duration
      changed the NNT for ibuprofen compared with placebo, but less for rofecoxib,
      reflecting longer duration of action of rofecoxib. Reporting for each treatment
      group the percentage of patients with 25, 50 and 75% pain relief at various times
      after dose, and reporting the proportion of patients with good or complete pain
      relief, and inadequate pain relief, at each time point, would improve acute pain
      trial reporting.

PMID- 15979793
TI  - Iatrogenic (para-) spinal abscesses and meningitis following injection therapy
      for low back pain.
AB  - Low back pain is often treated with paraspinal injections of analgesics and
      steroids. Infectious complications of these techniques are rare but they can
      potentially hold high risks for the patients. History and clinical data of all
      patients admitted to a neurological unit suffering from community acquired
      purulent meningitis were prospectively analyzed during an 8 year interval (1992
      and 2000) with special regard to the previous medical history. One hundred and
      twenty eight patients were included in the study. Eight out of 128 patients
      (6.25%) had a history of single or repeated paravertebral (4/8), facet-joint
      (2/8), peridural (1/8) or spinal (1/8) injections 2-21 days before admission to
      the hospital. In six out of eight patients either Staphylococcus aureus (4/8) or
      coagulase-negative staphylococci (2/8) were found in the cerebro spinal fluid
      (CSF), in two patients no causative organism was detected. One patient died,
      three survived with sequel. Repeated paraspinal, peridural or spinal injections
      with analgesic drugs in combination with corticosteroids hold a risk for
      parameningeal inoculation of bacteria resulting in paraspinal, spinal, and
      epidural abscesses or meningitis. The absolute frequency of these complications
      may be rare but they are responsible for a considerable proportion of community
      acquired purulent CNS infections.

PMID- 15979794
TI  - The Fear of Pain Questionnaire (FPQ): further psychometric examination in a non
      clinical sample.
AB  - The present study sought to examine psychometric properties of the Fear of Pain
      Questionnaire (FPQ), a measure of pain-related fear, in a sample of
      undergraduates. Confirmatory factor analysis confirmed the previously reported
      three-factor model of the FPQ (e.g. severe pain, minor pain, medical pain), but
      some items may be redundant. With respect to the reliability of the FPQ, both the
      FPQ and the subscales showed good internal consistency and test-retest stability
      was moderate to good. Convergent and predictive validity of the FPQ (and the
      subscales) were partly supported by moderate correlations with related constructs
      and with self-reported fear associated with three experimental pain tests.
      Discriminant validity of the FPQ (and the subscales) was partly supported by low
      correlations with unrelated self-report measures. Moreover, modest correlation
      coefficients were found between the FPQ and other pain-related measures. Finally,
      the minor pain subscale of the FPQ accounted for pain intensity scores on the
      ischemic pain test and the remaining subscales and the FPQ total scores accounted
      for pain tolerance on the electrical stimulation test and the thermal pain test.
      Results are discussed and directions for future research are provided.

PMID- 15979795
TI  - The relationship between religion/spirituality and physical health, mental
      health, and pain in a chronic pain population.
AB  - This study sought to better understand the relationship between
      religion/spirituality and physical health and mental health in 122 patients with
      chronic musculoskeletal pain. The current study conceptualized
      religion/spirituality as a multidimensional factor, and measured it with a new
      measure of religion/spirituality for research on health outcomes (Brief
      Multidimensional Measure of Religion/Spirituality). Pain patients' religious and
      spiritual beliefs appear different than the general population (e.g. pain
      patients feel less desire to reduce pain in the world and feel more abandoned by
      God). Hierarchical multiple regression analyses revealed significant associations
      between components of religion/spirituality and physical and mental health.
      Private religious practice (e.g. prayer, meditation, consumption of religious
      media) was inversely related to physical health outcomes, indicating that those
      who were experiencing worse physical health were more likely to engage in private
      religious activities, perhaps as a way to cope with their poor health.
      Forgiveness, negative religious coping, daily spiritual experiences, religious
      support, and self-rankings of religious/spiritual intensity significantly
      predicted mental health status. Religion/spirituality was unrelated to pain
      intensity and life interference due to pain. This study establishes relationships
      between religion/spirituality and health in a chronic pain population, and
      emphasizes that religion/spirituality may have both costs and benefits for the
      health of those with chronic pain.

PMID- 15979796
TI  - Towards a new taxonomy of idiopathic orofacial pain.
AB  - There is no current consensus on the taxonomy of the different forms of
      idiopathic orofacial pain (stomatodynia, atypical odontalgia, atypical facial
      pain, facial arthromyalgia), which are sometimes considered as separate entities
      and sometimes grouped together. In the present prospective multicentric study, we
      used a systematic approach to help to place these different painful syndromes in
      the general classification of chronic facial pain. This multicenter study was
      carried out on 245 consecutive patients presenting with chronic facial pain (>4
      months duration). Each patient was seen by two experts who proposed a diagnosis,
      administered a 111-item questionnaire and filled out a standardized 68-item
      examination form. Statistical processing included univariate analysis and several
      forms of multidimensional analysis. Migraines (n=37), tension-type headache
      (n=26), post-traumatic neuralgia (n=20) and trigeminal neuralgia (n=13) tended to
      cluster independently. When signs and symptoms describing topographic features
      were not included in the list of variables, the idiopathic orofacial pain
      patients tended to cluster in a single group. Inside this large cluster, only
      stomatodynia (n=42) emerged as a distinct homogenous subgroup. In contrast,
      facial arthromyalgia (n=46) and an entity formed with atypical facial pain (n=25)
      and atypical odontalgia (n=13) could only be individualised by variables
      reflecting topographical characteristics. These data provide grounds for an
      evidence-based classification of idiopathic facial pain entities and indicate
      that the current sub-classification of these syndromes relies primarily on the
      topography of the symptoms.

PMID- 15979797
TI  - Heritability of symptoms in the neuroma model of neuropathic pain: replication
      and complementation analysis.
AB  - Applying genetic selection pressure to an outbred population of albino rats, we
      have derived lines that show consistently high versus low pain phenotype in the
      neuroma model of neuropathic pain. Trait segregation developed rapidly,
      replicating earlier observations using this methodology. The resulting novel
      selection lines, designated nHA and nLA, share a common genetic background but
      have dramatically contrasting neuropathic pain behavior. In addition to
      confirming that the pain trait selected is heritable (estimated realized
      heritability h(2)=0.31), we have refreshed the availability of this research
      resource, namely animals of uniform genetic background but with contrasting pain
      phenotype. Crossing nHA rats with animals of the high (recessive) line from the
      earlier selection program (HA) yielded offspring almost uniformly high in pain
      phenotype. This complementation analysis indicates that the same gene(s) was
      selected in both selection programs, attesting to its unique salience in
      determining pain phenotype in the neuroma model.

PMID- 15979798
TI  - pain1: a neuropathic pain QTL on mouse chromosome 15 in a C3HxC58 backcross.
AB  - We have produced a backcross (BC) population of 267 mice from the parental
      strains C3H/HeN and C58/J. The mice were phenotyped for neuropathic pain using
      the neuroma model. Subsequently all BC mice were genotyped in a region of
      chromosome 15 that has been previously suggested to contain a quantitative trait
      locus (QTL) for this trait. We have confirmed the linkage of the QTL, named
      pain1, to the central region of chromosome 15. Our finding provides the necessary
      robustness to justify efforts towards identification of the underlying gene.

PMID- 15979799
TI  - Inhibition of ERK phosphorylation decreases nociceptive behaviour in
      monoarthritic rats.
AB  - In this study we investigated the role of the activation of the extracellular
      signal-regulated kinases 1 and 2 (ERK) in chronic inflammatory articular
      nociception. Monoarthritis was induced in the left ankle of Wistar rats by
      injection of complete Freund's adjuvant (CFA). Movement of the inflamed joint
      increased ERK phosphorylation in neurones of the superficial and deep ipislateral
      dorsal horn laminae of L3-L5 spinal cord segments. Spinal immunoreactivity to
      phosphoERK was more intense in animals in which the inflammation lasted longer, 7
      days or more, than in rats with less time of inflammation. PhosphoERK levels were
      transient, since 2h after ankle stimulation spinal immunoreaction had almost
      disappeared. PhosphoERK immunoreactivity was not induced by movement of ankles
      from non-arthritic control animals, neither in monoarthritic rats in which the
      inflamed ankle was not stimulated. Intrathecal administration of PD 98059, an
      inhibitor of ERK phosphorylation, reduced nociceptive behaviour induced by the
      ankle bend test in monoarthritic rats. The anti-nociceptive effect of PD 98059
      was more prominent and in animals with short lasting (4 days) than in animals
      with longer (14 days) monoarthritis. Taken together, these findings suggest that
      ERK phosphorylation in spinal cord neurones plays an important role in chronic
      inflammatory articular pain and that its inhibition may provide significant anti
      nociception.

PMID- 15979800
TI  - Detection of Histomonas meleagridis in turkeys cecal droppings by PCR
      amplification of the small subunit ribosomal DNA sequence.
AB  - Histomonas meleagridis is a protozoan parasite that may cause histomoniasis, a
      disease of gallinaceous fowl characterized by necrotic typhlitis, hepatitis and
      high mortality. Diagnosis of this disease is based on direct identification or on
      cultivation of the parasite. With the aim of developing more sensitive, rapid and
      useful tools for parasite detection, PCR that amplified a DNA target of 209 pb of
      the 18S rRNA gene was designed to detect the genome of H. meleagridis and to
      differentiate it from the genome of Tetratrichomonas gallinarum, another common
      protozoan parasite of fowl. The sensitivity of the test was evaluated using
      serial diluted samples of cultured H. meleagridis and showed positive
      amplification for concentrations comprised between 10 and 10(-1)parasites/ml of
      culture. The sensitivity for cecal droppings samples was assessed using spiked
      material and was comprised between 3 x 10(3) and 3 x 10(5)parasites/ml of stool.
      The reliability of the PCR for the detection of Histomonas infection was also
      evaluated by experimental infection of turkeys. Results of the PCR appeared to be
      in agreement with the development of the clinical signs and of the cecal lesions.
      The PCR developed in this study may be a useful tool in the detection and
      identification of H. meleagridis for rapid, routine screening as a supplement to
      direct identification or cultivation of the parasite.

PMID- 15979801
TI  - Muscle distribution of sylvatic and domestic Trichinella larvae in production
      animals and wildlife.
AB  - Only a few studies have compared the muscle distribution of the different
      Trichinella genotypes. In this study, data were obtained from a series of
      experimental infections in pigs, wild boars, foxes and horses, with the aim of
      evaluating the predilection sites of nine well-defined genotypes of Trichinella.
      Necropsy was performed at 5, 10, 20 and 40 weeks post inoculation. From all host
      species, corresponding muscles/muscle groups were examined by artificial
      digestion. In foxes where all Trichinella species established in high numbers,
      the encapsulating species were found primarily in the tongue, extremities and
      diaphragm, whereas the non-encapsulating species were found primarily in the
      diaphragm. In pigs and wild boars, only Trichinella spiralis, Trichinella
      pseudospiralis and Trichinella nelsoni showed extended persistency of muscle
      larvae (ML), but for all genotypes the tongue and the diaphragm were found to be
      predilection sites. This tendency was most obvious in light infections. In the
      horses, T. spiralis, Trichinella britovi, and T. pseudospiralis all established
      at high levels with predilection sites in the tongue, the masseter and the
      diaphragm. For all host species, high ML burdens appeared to be more evenly
      distributed with less obvious predilection than in light infections; predilection
      site muscles harbored a relatively higher percent of the larval burden in light
      infections than in heavy infections. This probably reflects increasing occupation
      of available muscle fibers as larger numbers of worms accumulate. Predilection
      sites appear to be influenced primarily by host species and secondarily by the
      age and level of infection.

PMID- 15979802
TI  - Endoparasites in calves of beef cattle herds: management systems dependent and
      genetic influences.
AB  - Prevalences and intensities of excretion of faecal stages of Giardia duodenalis,
      Cryptosporidium parvum, Eimeria spp., Strongyloides papillosus and strongyles
      were determined in a German upland area in German Angus (GA) and German Simmental
      (GS) suckler of beef cattle herds covering two winter housing periods and the
      grazing season between them. Influences of the housing systems applied
      (maintenance on deep litter with (DL+) and without run-out (DL--), on slatted
      floor (SF) or by winter run-out yarding (WO)), breed differences and genetic
      influences by the sire were determined by statistical analyses; levels of IgG
      antibodies to E. bovis antigen were measured by ELISA. G. duodenalis was observed
      with a maximum prevalence of 38% in 4 weeks old calves, a cumulative incidence of
      58% 9 weeks after birth and with generally low intensities. C. parvum infections
      were relatively rare with cumulative incidences of 20--25% in week 5 after birth.
      Highest prevalences were associated with housing system DL-- and a long-lasting
      calving period. Cumulative incidence of Eimeria spp. was almost 100%. E. bovis
      predominated by far followed by E. ellipsoidalis/zuernii. Mean maximum intensity
      of 1000 OpG occurred in week 7 after birth. Up to an age of the calves of 7 weeks
      >75% of all oocysts belonged to E. bovis. Prevalences and excretion intensities
      were lowest under the housing conditions SF and WO. Maternal antibodies in calves
      to E. bovis antigen were directly and inversely correlated with mean OpG values
      in GA and GS calves, respectively. S. papillosus was common with a cumulative
      incidence of 53% 9 weeks after birth and occurred independent of the housing
      system. Mean strongyle egg prevalence was 50% with 50--100 EpG by means
      throughout the grazing season. Egg excretion intensity in the early months of
      grazings was correlated with the age of the calves at turnout to pasture. Under
      the conditions of housing system DL-- GA calves could better control S.
      papillosus infections than GS calves whereas the latter were generally more
      effective in controlling the protozoa. Results of ANCOVA suggest significant
      paternal influences on S. papillosus infections in both breeds and on the
      protozoal infections in GA calves. The former could be disclosed independent of
      the housing system whereas environmental factors played an important role in the
      latter cases.

PMID- 15979803
TI  - Re-emergence of trichinellosis in southeastern Europe due to political and
      economic changes.
AB  - The countries of southeastern Europe including the Balkan region and bordering
      countries - Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Greece, Hungary,
      Macedonia, Romania, Serbia and Montenegro, Slovenia, and the European part of
      Turkey - occupy a very important strategic position and represent a land bridge
      between Europe and Asia. In the majority of southeastern European countries,
      cases of trichinellosis among the human and animal populations were described in
      the late 19th or early 20th centuries. Trichinella infections among wildlife were
      also described in the aforementioned countries. Today, the prevalence of
      trichinellosis is different between the Balkans and bordering countries. A high
      prevalence of trichinellosis in domestic animals and humans has been reported in
      Bulgaria, Serbia and Montenegro, Romania and Croatia. A moderate prevalence was
      found in Bosnia and Herzegovina. In Hungary, human trichinellosis has not been
      present for a long period of time. However, sporadic cases were recorded in swine
      over the last 2 years. Trichinellosis has not been found among domestic animals
      and humans in Greece and Macedonia in recent years while in Turkey and Slovenia
      human trichinellosis is sporadic. The re-emergence of trichinellosis is connected
      with the changes in the social and political systems in Bulgaria and Romania. In
      Serbia and Montenegro as well in Croatia, however, a re-emergence of
      trichinellosis was due not only to political and social changes but also to wars
      that took place in these countries during the last years of the 20th century.
      Social, economic and political factors responsible for the re-emergence of
      trichinellosis in southeast European countries are discussed in this
      communication.

PMID- 15979804
TI  - Central nervous system metastases in breast cancer patients administered
      trastuzumab.
AB  - Amplification or over-expression of the HER2/neu receptor is present in 20-30% of
      invasive breast cancers and in 60% of intraductal breast carcinomas. Patients
      with HER2/neu gene aberrations have more aggressive disease, frequent disease
      recurrence and a shorter survival. Trastuzumab (herceptin) is a monoclonal
      antibody selectively directed against the HER2/neu receptor. The addition of
      trastuzumab to chemotherapy in HER2/neu-positive advanced breast cancer patients
      has increased complete and partial response rates, and prolonged time to
      progression and overall survival. However, a relatively common failure site in
      patients administered trastuzumab is the central nervous system (CNS). CNS
      metastases in these patients seem to develop despite responses achieved in
      extracerebral sites. This pattern of failure has mainly been attributed to the
      lack of trastuzumab penetration to the CNS owing to the high molecular weight
      (145 kDa) of this molecule. Additionally, increased risk of CNS relapse may be
      associated with improved systemic control of extracerebral metastases and
      prolonged survival without brain protection (a sanctuary site). Finally, it was
      postulated that HER2/neu over-expression and/or amplification might predispose to
      brain metastases. The aim of this article is to discuss the pathophysiology of
      this phenomenon and its clinical implications.

PMID- 15979805
TI  - Implication of cyclin-dependent kinase 5 in the neuroprotective properties of
      lithium.
AB  - Although numerous studies have demonstrated a neuroprotective and anti-apoptotic
      role of lithium in neuronal cell cultures, the precise mechanism by which this
      occurs, remains to be elucidated. In this study, we evaluated the lithium
      mediated neuroprotection against colchicine-induced apoptosis in cultured
      cerebellar granule neurons. Previously, it has been demonstrated that colchicine
      mediates apoptosis in cerebellar granule neurons through cytoskeletal alteration
      and activation of an intrinsic pro-apoptotic pathway. Recently we also
      demonstrated a potential role of cyclin-dependent kinase 5 (cdk5) in this
      pathway. Here we report that colchicine induces dephosphorylation in Ser-9 and
      phosphorylation in Tyr-216, and thus activation, of glycogen synthase kinase
      3beta in cerebellar granule neurons, and that this modification is inhibited by
      the presence of 5 mM lithium. However, the selective glycogen synthase kinase
      3beta inhibitors SB-415286 and SB-216763 were unable to prevent colchicine
      induced apoptosis in these cells, suggesting that the anti-apoptotic activity of
      lithium is not mediated by glycogen synthase kinase-3beta under these conditions.
      On the other hand, 5 mM lithium prevented the colchicine-induced increase in cdk5
      expression and breakdown of cdk5/p35 to cdk5/p25. In addition, we show that up
      regulation of cdk5/p25 is unrelated to inhibition of the activity of myocyte
      enhancer factor 2, a pro-survival transcription factor. These data suggest a
      previously undescribed neuroprotective mechanism of lithium associated with the
      modulation of cdk5/p35 or cdk5/p25 expression.

PMID- 15979806
TI  - Chemokine receptor 5 antagonist D-Ala-peptide T-amide reduces microglia and
      astrocyte activation within the hippocampus in a neuroinflammatory rat model of
      Alzheimer's disease.
AB  - Chronic neuroinflammation plays a prominent role in the progression of
      Alzheimer's disease. Reactive microglia and astrocytes are observed within the
      hippocampus during the early stages of the disease. Epidemiological findings
      suggest that anti-inflammatory therapies may slow the onset of Alzheimer's
      disease. Chemokine receptor 5 (CCR5) up-regulation may influence the recruitment
      and accumulation of glia near senile plaques; activated microglia express CCR5
      and reactive astrocytes express chemokines. We have previously shown that
      neuroinflammation induced by chronic infusion of lipopolysaccharide into the 4th
      ventricle reproduces many of the behavioral, neurochemical, electrophysiological
      and neuropathological changes associated with Alzheimer's disease. The current
      study investigated the ability of D-Ala-peptide T-amide (DAPTA), a chemokine
      receptor 5 chemokine receptor antagonist of monocyte chemotaxis, to influence the
      consequences of chronic infusion of lipopolysaccharide. DAPTA (0.01 mg/kg, s.c.,
      for 14 days) dramatically reduced the number of activated microglia and
      astrocytes, as compared with lipopolysaccharide-infused rats treated with
      vehicle. DAPTA treatment also reduced the number of immunoreactive cells
      expressing nuclear factor kappa binding protein, a prominent component of the
      proinflammatory cytokine signaling pathway. The present study suggests that DAPTA
      and other CCR5 antagonists may attenuate critical aspects of the
      neuroinflammation associated with Alzheimer's disease.

PMID- 15979807
TI  - Neuronal gap junctions in the mouse main olfactory bulb: morphological analyses
      on transgenic mice.
AB  - In the present study we analyzed the structural features of extraglomerular gap
      junction-forming processes in mouse olfactory bulb electron microscopically. This
      work complements a previous study in which we analyzed the structural features of
      neuronal gap junction-forming processes within the glomerulus itself. Furthermore
      we examined connexin 36 expressing cells in the mouse olfactory bulb by analyzing
      transgenic mice in which the connexin 36 coding sequence was replaced with
      histological reporters. In extraglomerular regions, the mitral/tufted cell
      somata, dendrites and axon hillocks made gap junctions and mixed synapses with
      interneuronal processes. These gap junctions and synapses were associated with
      various types of interneuronal processes, including a particular type of sheet
      like or calyx-like process contacting the somata or large dendrites of
      mitral/tufted cells. In the olfactory bulbs of the transgenic mice, connexin 36
      was expressed in mitral cells, tufted cells, presumed granule cells and
      periglomerular cells. Multiple immunofluorescent labelings further revealed that
      presumed interneurons expressing connexin 36 in the periglomerular region rarely
      expressed calbindin, calretinin or tyrosine hydroxylase and are likely to
      comprise a chemically uncharacterized class of neurons. Similarly, interneurons
      expressing connexin 36 in the granule cell layer were rarely positive for
      calretinin, which was expressed in numerous presumed granule cells in the mouse
      main olfactory bulb. In summary, these findings revealed that mitral/tufted cells
      make gap junctions with diverse types of neurons; in the glomeruli gap junction
      forming interneuronal processes originated from some types of periglomerular
      cells but others from a hitherto uncharacterized neuron type(s), and in the
      extraglomerular region gap-junction forming processes originate mainly from a
      subset of cells within the granule cell layer.

PMID- 15979808
TI  - Specialization in pyramidal cell structure in the sensory-motor cortex of the
      vervet monkey (Cercopethicus pygerythrus).
AB  - Recent studies have revealed systematic differences in the pyramidal cell
      structure between functionally related cortical areas of primates. Trends for a
      parallel in pyramidal cell structure and functional complexity have been reported
      in visual, somatosensory, motor, cingulate and prefrontal cortex in the macaque
      monkey cortex. These specializations in structure have been interpreted as being
      fundamental in determining cellular and systems function, endowing circuits in
      these different cortical areas with different computational power. In the present
      study we extend our initial finding of systematic specialization of pyramidal
      cell structure in sensory-motor cortex in the macaque monkey [Cereb Cortex 12
      (2002) 1071] to the vervet monkey. More specifically, we investigated pyramidal
      cell structure in somatosensory and motor areas 1/2, 5, 7, 4 and 6. Neurones in
      fixed, flat-mounted, cortical slices were injected intracellularly with Lucifer
      Yellow and processed for a light-stable 3,3'-diaminobenzidine reaction product.
      The size of, number of branches in, and spine density of the basal dendritic
      arbors varied systematically such that there was a trend for increasing
      complexity in arbor structure with progression through 1/2, 5 and 7. In addition,
      cells in area 6 were larger, more branched, and more spinous than those in area
      4.

PMID- 15979809
TI  - Spatio-temporal cholinergic modulation in cultured networks of rat cortical
      neurons: evoked activity.
AB  - We studied the effects of carbachol, a cholinergic agonist, on extracellularly
      evoked firing of networks in mature cultures of rat cortical neurons, using multi
      electrode arrays to monitor the activity of large numbers of neurons
      simultaneously. These cultures show evoked burst firing which propagates through
      dense synaptic connections. When a brief voltage pulse was applied to one
      extracellular electrode, spiking electrical responses were evoked in neurons
      throughout the network. The response had two components: an early phase,
      terminating within 30-80 ms, and a late phase which could last several hundreds
      of milliseconds. Action potentials evoked during the early phase were precisely
      timed, with only small jitter. In contrast, the late phase characteristically
      showed clusters of electrical activity with significant spatio-temporal
      fluctuations. The late phase was suppressed by applying a relatively small amount
      of carbachol (5 microM) in the external solution, even though the spontaneous
      firing rate was not significantly changed. Carbachol increased both the spike
      timing precision and the speed of propagation of population spikes, and
      selectively increased the firing coincidence in a subset of neuron pairs in the
      network, while suppressing late variable firing in responses. Hence, the results
      give quantitative support for the idea that cholinergic activation in the cortex
      has a general role of focusing or enhancing significant associative firing of
      neurons.

PMID- 15979810
TI  - The effect of a low dose of alcohol on allopregnanolone serum concentrations
      across the menstrual cycle in women with severe premenstrual syndrome and
      controls.
AB  - BACKGROUND: Neurosteroids have been proposed to play an important role in the
      interaction between alcohol and GABA(A) receptors and for the symptomatology of
      premenstrual dysphoric disorder (PMDD). The primary aim of this study was to
      investigate possible alcohol-induced changes in allopregnanolone serum
      concentrations across different menstrual cycle phases in women with severe
      premenstrual syndrome (PMS) and controls. METHODS: The allopregnanolone and
      cortisol responses to a low-dose of alcohol were evaluated in 14 women with and
      12 women without severe premenstrual syndrome in the follicular and late luteal
      phases. The effect of a 30-min intravenous alcohol infusion (0.2 g/kg) on
      allopregnanolone and cortisol serum concentrations was compared to placebo, and
      compared between cycle phases and groups. Blood samples for measuring
      allopregnanolone were taken at baseline 25, 55, and 75 min after the start of the
      alcohol infusion. RESULTS: In the late luteal phase, the alcohol infusion
      decreased allopregnanolone levels, compared to baseline levels as well as to
      placebo. The difference in allopregnanolone levels between alcohol and placebo
      was evident 25 min (P < 0.01), 55 min (P < 0.01), and 75 min (P < 0.05) after
      start of the infusion. There was no change in allopregnanolone levels during the
      alcohol infusion in the follicular phase. Also, no difference in alcohol-induced
      allopregnanolone response between PMS patients and control subjects was detected.
      Cortisol levels declined during both the placebo and alcohol infusion, but did
      not differ with respect to which infusion had been given. CONCLUSION: During the
      late luteal phase, independent of PMS diagnosis, the low-dose alcohol infusion
      resulted in decreasing peripheral allopregnanolone levels.

PMID- 15979811
TI  - Food hypersensitivity-immunologic (peripheral) or cognitive (central)
      sensitisation?
AB  - Patients with food hypersensitivity suffer poor quality of life and several
      unexplained health complaints, both abdominal and extra-abdominal. Part of the
      suffering is due to healthcare providers' neglect and poor insight, allowing a
      strong position for alternative medicine. Distinguishing food allergy from
      functional and organic disorders can be extremely difficult. We have found
      examination of faecal calprotectin and gut permeability to be useful for
      excluding organic disease, whilst conventional provocation tests for positive
      diagnosis of food hypersensitivity are cumbersome. Our new ultrasound provocation
      test has been promising, but we acknowledge that much work remains to be done
      before its sensitivity and specificity can be finally established. The majority
      of patients with self-reported food hypersensitivity have a non-allergic
      hypersensitivity disorder. We suggest that cognitive-emotional sensitisation at
      the brain level, and not peripheral (immunological) sensitisation, is a major
      pathogenetic mechanism by which the patients' various abdominal and extra
      abdominal health complaints are generated. Extensive activation of cognitive
      networks might be triggered by peripheral sensory mechanisms, often
      misinterpreted as 'food allergy'. Clearly, the approach to patients with food
      hypersensitivity should be interdisciplinary.

PMID- 15979812
TI  - Tobacco chippers report diminished autonomy over smoking.
AB  - We assessed tobacco chippers (n=35) for symptoms of diminished autonomy over
      tobacco use, which begins when symptoms present a barrier to smoking cessation.
      Although they reported each of the symptoms measured by the Hooked on Nicotine
      Checklist, chippers' level of autonomy was generally higher than that of regular
      smokers and their symptom intensity was low. The rank order of symptom prevalence
      in chippers and regular smokers was similar, and 40% of chippers had failed at
      least one cessation attempt. Only 23% of chippers reported full autonomy over
      their smoking. Although chippers may not warrant a dependence diagnosis, they may
      benefit from help with cessation. Autonomy over smoking may be a more useful
      basis than cigarette consumption rates for classifying smokers.

PMID- 15979813
TI  - Recent drinking consequences, motivation to change, and changes in alcohol
      consumption over a three month period.
AB  - Little is known about what type of drinking related consequences may enhance
      motivation to change or may hinder behavior change over time. In order to examine
      this research question, 120 adult participants abusing alcohol were administered
      the Drinker Inventory of Consequences-Recent (DrInC-R), the Brief Readiness to
      Change Questionnaire (BRTC), and the Steady Pattern Chart (SP). Subscale scores
      from the DrInC-R and the BRTC; and alcohol consumption as assessed by the SP at
      baseline and three month follow-up were retained for data analyses. Greater
      intrapersonal DrInC-R consequences scores significantly predicted greater
      contemplation stage scores (R2=.37, p<.001), and lower precontemplation stage
      scores (R2=.32, p<.001), and DrInC-R impulse control and interpersonal
      consequences scores significantly predicted alcohol consumption at three month
      follow-up after controlling for baseline consumption (R2=.50, p<.001). Increased
      awareness of intrapersonal drinking related consequences may motivate change,
      whereas numbers of impulse control and interpersonal consequences may predict
      changes in drinking behavior over the short-term.

PMID- 15979814
TI  - Pretreatment cue reactivity predicts end-of-treatment smoking.
AB  - Although a substantial body of literature has established a relationship between
      cue reactivity and theoretically relevant addiction variables, the association
      with treatment process variables remains largely unexplored. In the current
      investigation, 62 smokers participated in a smoking cue reactivity study, and
      subsequently enrolled in a smoking cessation program. Hierarchical regressions
      revealed mean heart rate during the cue presentation phase of the laboratory
      based assessment predicted final session smoking rate and expired CO level.
      Fagerstrom Tolerance Questionnaire score also predicted final session smoking
      rate. To the extent that rate reduction serves as an index of treatment progress,
      it may be of value in future cue reactivity research.

PMID- 15979816
TI  - Obesity and dose individualization in cancer chemotherapy: the role of body
      surface area and body mass index.
AB  - It is generally accepted that anti-neoplastic chemotherapy dose should be
      calculated according to body surface area (BSA). This approach does not account
      for the presence of obesity. Hence, patients with the same BSA will receive the
      same chemotherapy dose, regardless the presence of obesity. Since this may cause
      of toxicity in some obese patients, practice of limit BSA is usual. Currently,
      the body mass index (BMI) is largely used as a marker of obesity and both BSA and
      BMI include only height (h) and weight(w) in their formula. We put forward the
      hypothesis that the BMI should also be taken in account for calculation of
      chemotherapy dose for obese patients (BMI > 30 kg/m2). In this article, we
      present a correction to BSA (CBSA) based on the BMI to be tested in obese
      patients. Our main result is given by the
      equationCBSA=K(alpha1h(alpha2+2kappa)w(alpha3-kappa)),whereand kappa, alpha1,
      alpha2, alpha3 are constants. We show examples of how to calculate the CBSA. This
      simple strategy may limit drug exposition and maintain greater efficacy than a
      fixed limitation of BSA.

PMID- 15979815
TI  - Do behavioral smoking reduction approaches reach more or different smokers? Two
      studies; similar answers.
AB  - There is a need for innovative approaches capable of reaching smokers who would
      not otherwise participate in efforts to modify their smoking. This paper reports
      on two studies to determine whether a smoking reduction intervention would appeal
      to additional or different types of smokers than do cessation interventions.
      Study 1 attempted to contact 160 HMO smokers scheduled for outpatient surgeries.
      In Study 2, actual pilot reduction and cessation programs were offered to 531
      smokers about to undergo out-patient surgeries or procedures. In Study 1, 39% of
      those eligible elected smoking reduction; and 38% selected cessation. In Study 2
      of those eligible, 22% began participation in the smoking reduction program; 12%
      preferred a cessation approach; and 65% declined. There were few demographic or
      smoking history differences among those who elected smoking reduction, cessation,
      or declined. Among this understudied population, a sizable proportion in both
      studies agreed to participate in smoking reduction. If replicated, this suggests
      that comprehensive programs that include a smoking reduction component could
      substantially increase their reach.

PMID- 15979817
TI  - The contribution of integrated PET/CT to the evolving definition of treatment
      volumes in radiation treatment planning in lung cancer.
AB  - PURPOSE: Positron emission tomography (PET) with the glucose analog [18F]fluro-2
      deoxy-D-glucose (FDG) has been accepted as a valuable tool for the staging of
      lung cancer, but the use of PET/CT in radiation treatment planning is still not
      yet clearly defined. By the use of (PET/computed tomography (CT) images in
      treatment planning, we were able to define a new gross treatment volume using
      anatomic biologic contour (ABC), delineated directly on PET/CT images. We
      prospectively addressed three issues in this study: (1) How to contour treatment
      volumes on PET/CT images, (2) Assessment of the degree of correlation between CT
      based gross tumor volume/planning target volume (GTV/PTV) (GTV-CT and PTV-CT) and
      the corresponding PET/CT-based ABC treatment volumes (GTV-ABC and PTV-ABC), (3)
      Magnitude of interobserver (radiation oncologist planner) variability in the
      delineation of ABC treatment volumes (using our contouring method). METHODS AND
      MATERIALS: Nineteen patients with Stages II-IIIB non-small-cell lung cancer were
      planned for radiation treatments using a fully integrated PET/CT device. Median
      patient age was 74 years (range: 52-82 years), and median Karnofsky performance
      status was 70. Thermoplastic or vacuum-molded immobilization devices required for
      conformal radiation therapy were custom fabricated for the patient before the
      injection of [18]f-FDG. Integrated, coregistered PET/CT images were obtained and
      transferred to the radiation planning workstation (Xeleris). While the PET data
      remained obscured, a CT-based gross tumor volume (GTV-CT) was delineated by two
      independent observers. The PTV was obtained by adding a 1.5-cm margin around the
      GTV. The same volumes were recontoured using PET/CT data and termed GTV-ABC and
      PTV-ABC, correspondingly. RESULTS: We observed a distinct "halo" around areas of
      maximal standardized uptake value (SUV). The halo was identified by its distinct
      color at the periphery of all areas of maximal SUV uptake, independent of PET/CT
      gain ratio; the halo had an SUV of 2 +/- 0.4 and thickness of 2 mm +/- 0.5 mm.
      Whereas the center of our contoured treatment volume expressed the maximum SUV
      level, a steady decline of SUV was noted peripherally until SUV levels of 2 +/-
      0.4 were reached at the peripheral edge of our contoured volume, coinciding with
      the observed halo region. This halo was always included in the contoured GTV-ABC.
      Because of the contribution of PET/CT to treatment planning, a clinically
      significant (> or =25%) treatment volume modification was observed between the
      GTV-CT and GTV-ABC in 10/19 (52%) cases, 5 of which resulted in an increase in
      GTV-ABC volume vs. GTV-CT. The modification of GTV between CT-based and PET/CT
      based treatment planning resulted in an alteration of PTV exceeding 20% in 8 out
      of 19 patients (42%). Interobserver GTV variability decreased from a mean volume
      difference of 28.3 cm3 (in CT-based planning) to 9.12 cm3 (in PET/CT-based
      planning) with a respective decrease in standard deviation (SD) from 20.99 to
      6.47. Interobserver PTV variability also decreased from 69.8 cm3 (SD +/- 82.76)
      in CT-based planning to 23.9 cm3 (SD +/- 15.31) with the use of PET/CT in
      planning. The concordance in treatment planning between observers was increased
      by the use of PET/CT; 16 (84%) had < or =10% difference from mean of GTVs using
      PET/CT compared to 7 cases (37%) using CT alone (p = 0.0035). CONCLUSION:
      Position emission tomography/CT-based radiation treatment planning is a useful
      tool resulting in modification of GTV in 52% and improvement of interobserver
      variability up to 84%. The use of PET/CT-based ABC can potentially replace the
      use of GTV. The anatomic biologic halo can be used for delineation of volumes.

PMID- 15979818
TI  - Identification of genetic markers for Mycobacterium pinnipedii through genome
      analysis.
AB  - Tuberculosis in seals is caused by Mycobacterium pinnipedii, a member of the
      Mycobacterium tuberculosis complex. In this study, we evaluated the extent of
      genetic variability among Mycobacterium bovis and M. pinnipedii by microarray
      based comparative genomics. We identified two deletions that are exclusive to M.
      pinnipedii: PiD1 that removes the orthologues of the M. tuberculosis genes
      Rv3530c and Rv3531c, and PiD2 that encompasses genes Rv1977 and Rv1978.
      Interestingly, a deletion overlapping the previously described RD2 region was
      identified in some isolates of Mycobacterium microti and further characterised.

PMID- 15979819
TI  - Molecular characterization of phytoplasmas in lilies with fasciation in the Czech
      Republic.
AB  - Lilium spp. with symptoms of severe fasciation were observed in Southern and
      central Bohemia during the period 1999-2003. Nucleic acids extracted from
      symptomatic and asymptomatic plants were used in nested-PCR assays with primers
      amplifying 16S-23S rRNA sequences specific for phytoplasmas. The subsequent
      nested-PCR with phytoplasma group-specific primers followed by RFLP analyses and
      the 16S ribosomal gene sequencing, allowed classification of the detected
      phytoplasmas in the aster yellows group, subgroups 16SrI-B and 16SrI-C alone, and
      in mixed infection. Samples infected by 16SrI-C phytoplasmas showed different
      overlapping RFLP profiles after TruI digestion of R16F2/R2 amplicons. Two of
      these amplicons were sequenced, one of them directly and the other after cloning;
      sequence analyses and blast alignment confirmed the presence of two different
      overlapping patterns in samples studied. The sequences obtained were closely
      related, respectively, to operon A and operon B ribosomal sequences of the clover
      phyllody phytoplasma. Direct PCR followed by RFLP analyses of the tuf gene with
      two restriction enzymes showed no differences from reference strain of subgroup
      16SrI-C. Infection with aster yellows phytoplasmas of 16SrI-B subgroup in
      asymptomatic lilies cv. Sunray was also detected.

PMID- 15979820
TI  - Molecular monitoring and characterization of the faecal microbiota of healthy
      dogs during fructan supplementation.
AB  - The large intestine of dogs contains a complex microbial ecosystem with
      predominance of streptococci, bifidobacteria, lactobacilli, Bacteroides and
      Clostridium. Generally, this predominant microbiota in dogs is relatively stable
      in time but much less is known about its taxonomic composition. Moreover, almost
      no studies have been conducted to investigate this stability of the faecal
      microbial population in dogs upon prebiotic administration. The objective of the
      present study was to monitor possible changes in faecal microbiota of seven
      healthy adult dogs related to the administration of two fructans, oligofructose
      and inulin. For this purpose, population fingerprints generated by denaturing
      gradient gel electrophoresis (DGGE) analysis of universal V3 16 S rRNA gene PCR
      amplicons were compared between control (baseline) samples and samples collected
      after prebiotic feeding. From these DGGE gels, marked changes were observed in
      the faecal microbiota between subjects and before and after fructan
      administration. One DGGE band that appeared or intensified after fructan intake
      was further analyzed. Sequence analysis could attribute this band to a member of
      the Streptococcus bovis-equinus group. Following cultivation on MRS medium, a set
      of faecal isolates that most likely represent the stimulated streptococci were
      allocated to the species Streptococcus lutetiensis by (GTG)(5)-PCR fingerprinting
      and partial 16 S rRNA and sodA gene sequencing. The data provided in this study
      demonstrate the ability of fructans to influence the bacterial composition of the
      gut microbiota in healthy dogs. More work is needed to unravel the relevance of
      S. lutetiensis or other autochthonous organisms of the dog gut as target groups
      for prebiotic supplementation.

PMID- 15979821
TI  - Lipolytic activity from Halobacteria: screening and hydrolase production.
AB  - Strains of Halobacteria from an Algerian culture collection were screened for
      their lipolytic activity against p-nitrophenyl butyrate (PNPB) and p-nitrophenyl
      palmitate (PNPP). Most strains were active on both esters and 12% hydrolyzed
      olive oil. A strain identified as Natronococcus sp. was further studied. It grew
      optimally at 3.5 M NaCl, pH 8 and 40 degrees C. An increase in temperature
      shifted the optimum salt concentration range for growth from a wider range of 2-4
      M, obtained at 25-30 degrees C, to a narrower range of 3.5-4 M, obtained at 35-40
      degrees C. At 45 degrees C the optimum salt concentration was 2 M. These results
      show a clear correlation between salt and temperature requirement. The optimum
      conditions for the production of hydrolytic activity during growth were: 3.5 M
      NaCl and pH 8 for PNPB hydrolytic activity and 4 M NaCl and pH 7.5 for PNPP
      hydrolytic activity; both at 40 degrees C. The clear supernatant of cells grown
      at 4 M NaCl showed olive oil hydrolysis activity (in presence of 4 M NaCl)
      demonstrating the occurrence of a lipase activity in this strain. To our
      knowledge, this is the first report of a lipase activity at such high salt
      concentration.

PMID- 15979822
TI  - Characterization of IS1501 mutants of Leptospira interrogans serovar pomona.
AB  - Leptospira interrogans is a diverse species in which individual serovars have
      distinctive restriction fragment length polymorphisms that are useful in strain
      identification. Many of these polymorphisms can be detected using hybridization
      probes derived from insertion sequences; an observation that suggests these IS
      elements are active and can transpose in L. interrogans. Two spontaneous mutants
      of L. interrogans serovar Pomona strain RZ11 were isolated by immune selection
      and characterized. Changes in the size and antigenicity of LPS from these mutants
      were detected. Genetic analysis showed that both mutants have additional copies
      of an IS3-like element, designated IS1501, that are not present in the parental
      strain. One mutant, GT211, has a single additional copy of IS1501, whereas the
      other mutant, GT210 has three additional copies of IS1501 relative to strain
      RZ11. IS1501 transposition generated 3-bp direct repeats from target sequences
      flanking the insertion site. RT-PCR analysis of transcripts at altered loci
      showed IS1501 transcripts extended into adjacent sequences. These data are the
      first to show spontaneous transposition of an endogenous Leptospira insertion
      sequence, and suggest that IS1501 may be capable of gene activation.

PMID- 15979823
TI  - Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene
      cluster of Aspergillus fumigatus.
AB  - Gliotoxin is a secondary metabolite produced by several fungi including the
      opportunistic animal pathogen Aspergillus fumigatus. It is a member of the
      epipolythiodioxopiperazine (ETP) class of toxins characterised by a disulphide
      bridged cyclic dipeptide. A putative cluster of 12 genes involved in gliotoxin
      biosynthesis has been identified in A. fumigatus by a comparative genomics
      approach based on homology to genes from the sirodesmin (another ETP)
      biosynthetic gene cluster of Leptosphaeria maculans. The physical limits of the
      cluster in A. fumigatus have been defined by bioinformatics and by identifying
      the genes that are co-regulated and whose timing of expression correlates with
      the production of gliotoxin in culture.

PMID- 15979824
TI  - Inter-genomic cross talk between mitochondria and the nucleus plays an important
      role in tumorigenesis.
AB  - Mitochondrial dysfunction is a hallmark of cancer cells. Consistent with this
      phenotype mutations in mitochondrial genome have been reported in all cancers
      examined to date. However, it is not clear whether mitochondrial genomic status
      in human cells affects nuclear genome stability and whether proteins involved in
      inter-genomic cross talk are involved in tumorigenesis. Using cell culture model
      and cybrid cell technology, we provide evidence that mitochondrial genetic status
      impacts nuclear genome stability in human cells. In particular our studies
      demonstrate 1) that depletion of mitochondrial genome (rho0) leads to chromosomal
      instability (CIN) reported to be present in variety of human tumors and 2) rho0
      cells show transformed phenotype. Our study also demonstrates that mitochondrial
      genetic status plays a key role in regulation of a multifunctional protein APE1
      (also known as Ref1 or HAP1) involved in transcription and DNA repair in the
      nucleus and the mitochondria. Interestingly we found that altered expression of
      APE1 in rho0 cells and tumorigenic phenotype can be reversed by exogenous
      transfer of wild type mitochondria in rho0 cells. Furthermore, we demonstrate
      that APE1 expression is altered in variety of primary tumors. Taken together,
      these studies suggest that inter-genomic cross talk between mitochondria and the
      nucleus plays an important role in tumorigenesis and that APE1 mediates this
      process.

PMID- 15979825
TI  - Analysis of the very large G-protein coupled receptor gene (Vlgr1/Mass1/USH2C) in
      zebrafish.
AB  - Very Large G-protein coupled Receptor-1 (VLGR1/Mass1/USH2C) is the largest known
      cell surface protein in vertebrates. Mutations in VLGR1 are associated with
      audiogenic epilepsy in mice and Usher syndrome (sensorineural deafness and
      retinitis pigmentosa) in humans. We characterized the zebrafish VLGR1 gene
      (vlgr1). It is 51% identical to human VLGR1 in amino acid sequence, but is 64%
      identical in the 7-transmembrane and cytoplasmic domains. It is 6199 amino acids
      in size and is encoded by a 19.2 kb mRNA. All introns correspond in location and
      phase to those of the human and mouse genes. In situ hybridization studies of
      zebrafish embryos demonstrate vlgr1 expression in the developing central nervous
      system, particularly in the hypothalamus, epiphysis and in the rhombic lips.
      Expression in the eye is associated with the optic nerve. Further studies using
      zebrafish may help ascertain the role of Vlgr1 in neural development.

PMID- 15979826
TI  - Differential expression of non-cytoplasmic Actinobacillus pleuropneumoniae
      proteins induced by addition of bronchoalveolar lavage fluid.
AB  - Actinobacillus (A.) pleuropneumoniae is the causative agent of a porcine
      pleuropneumonia occurring worldwide. In order to identify novel non-cytoplasmic
      putative virulence-associated proteins, we prepared fractions enriched in surface
      associated proteins for differential proteome analysis by two-dimensional (2D)
      gel electrophoresis and quadrupole time-of-flight mass spectrometry (Q-Tof MS).
      Bacteria grown under standard culture conditions were compared to an ex vivo
      model based on the addition of bronchoalveolar lavage fluid (BALF) to the culture
      media. Twelve proteins were found to be upregulated upon induction with BALF,
      among them a superoxide dismutase, a parvulin-like peptidy-prolyl isomerase, a
      polynucleotide phosphorylase and the highly immunogenic lipoprotein OmlA. Four of
      the proteins upregulated by BALF were additionally constitutively expressed by an
      isogenic A. pleuropneumoniae fur deletion mutant and could be identified by Q-Tof
      MS as the heat shock protein GroES, a putative dipeptide transporter, a putative
      metal ion transporter and a conserved protein of unknown function. In silico
      analysis of the putative promoter regions of the encoding genes revealed putative
      Fur boxes upstream of two genes, one of which encodes part of a putative metal
      ion transporter. An isogenic mutant with a deletion in this protein was
      constructed and designated as A. pleuropneumoniae Deltafui. Analysis of the
      mutant in an aerosol infection model revealed symptoms indistinguishable from
      those seen upon infection with wild type A. pleuropneumoniae. This result implies
      that not all proteins upregulated by BALF are directly involved in A.
      pleuropneumoniae virulence.

PMID- 15979827
TI  - Toxic oil syndrome: genetic restriction and immunomodulatory effects due to
      adulterated oils in a model of HLA transgenic mice.
AB  - Toxic oil syndrome (TOS) was described in Spain in 1981, due to the ingestion of
      contaminated rapeseed oil denatured with 2% aniline. More than 20,000 persons
      were affected, causing over 2500 deaths. Immunological findings were:
      eosinophilia, mRNA for Th2 cytokines (IL-4 and IL-5) in lungs, elevated total IgE
      and sIL-2R and increase of DR2 HLA class II phenotypic frequency in patients died
      by TOS. Our objective is to test the genetic restriction found in humans using
      HLA transgenic mice. Results show that mice expressing human DR2 and DQ6 (both in
      linkage disequilibrium), had higher percentage of eosinophils (DQ6) and IgE (DR2)
      than other transgenic mice tested (DR3 and DR4). Also, a Th2 shift was found in
      DR2 transgenic mice when toxic oil was administered with OVA. This has been
      corroborated by the IL-5 mRNA expression in 4 out of 6 lung tissues from TOS oil
      treated BALB/c mice. These data indicate that an immunological response was
      induced as consequence of the toxic administration. These results correlate with
      those found in TOS patients and reinforce the implication of genetic restrictions
      in the acquisition of toxic-mediated disease.

PMID- 15979828
TI  - Pre-treatment effects of trichloroethylene on the dermal absorption of the
      biocide, triazine.
AB  - Triazine is often added to cutting-fluid formulations in the metal-machining
      industry as a preservative. Trichloroethylene (TCE) is a solvent used for
      cleaning the cutting fluid or oil from the metal product. The purpose of this
      study was to examine the effect of TCE on the dermal absorption of triazine in an
      in vitro flow-through diffusion cell system. Skin sections were dosed topically
      with aqueous mixtures containing mineral oil or polyethylene glycol (PEG) spiked
      with (14)C-triazine. Some skin sections were simultaneously exposed to TCE while
      other skin sections were pre-treated with TCE daily for 4 days in vivo and then
      exposed to these mixtures in vitro. TCE pre-treatment almost doubled triazine
      permeability, but this pre-treatment had no effect on triazine diffusivity. The
      pre-treatment effects of TCE on triazine permeability appear to be more important
      in PEG-based mixtures than in the mineral oil-based mixtures. Simultaneous single
      exposure to TCE had little or no effect on triazine absorption. TCE absorption
      was significantly less than triazine absorption; however, cutting fluid additives
      had a more significant effect on TCE absorption than on triazine absorption. In
      summary, this study demonstrated that TCE pre-treatment can significantly alter
      the dermal permeability to triazine, and workers who are chronically exposed to
      this or similar cleansers may be at increased risk of absorbing related skin
      irritants.

PMID- 15979830
TI  - Paediatric formulations--getting to the heart of the problem.
AB  - Many medicines prescribed for children are unlicensed. Solid dosage forms present
      problems as children have difficulty swallowing whole tablets or capsules. When
      medicines are not licensed for children, it is unlikely that there will be a
      suitable, licensed liquid formulation and so extemporaneous liquid preparations
      (prepared at the dispensary or by GMP 'special' manufacturers) are often used.
      This study looked at a list of medicines commonly prescribed for children with
      cardiovascular conditions in an English specialist paediatric hospital and
      classified them according to licensed status and available formulations. As
      expected, most medicines used for children with cardiovascular problems were
      unlicensed and where this was the case, usually only 'special' liquids or
      extemporaneous preparations were available. Problems linked with formulations
      highlighted in this therapeutic category were: problems in dosing accuracy and
      unknown bioavailability of extemporaneous products, the use of potentially toxic
      excipients, and lack of access to modified release preparations for children.
      These problems are likely to extend to other paediatric therapeutic areas. There
      is currently a large, unmet need to improve formulations of commonly used
      paediatric medicines, both through licensing and standardising the production of
      extemporaneous and 'special' formulations. It is expected that the awaited
      European regulation will help to meet some of those needs.

PMID- 15979829
TI  - Developmental rate and ploidy of embryos produced by nuclear transfer with
      different activation treatments in cattle.
AB  - Bovine oocyte activation is one of the essential elements that determine the
      success of nuclear transfer and the subsequent development of cloned embryos.
      Three methods for oocyte activation, including 5 microM ionomycin (5 min, Group
      1) alone, ionomycin+1.9 mM 6-dimethylaminopurine (DMAP, 3h, Group 2), and
      ionomycin+10 microg/ml cycloheximide (CHX, 3h, Group 3) were compared for the
      development of embryos produced by somatic nuclear transfer (SCNT) to parthenotes
      and IVF counterparts. At 19-h post-activation/insemination (hpa/hpi), 27.5% of
      oocytes in Group 2 cleaved and this rate was greater (P<0.05) than other groups
      (Group 1, 2.1%; Group 3, 3.0%). None of the oocytes in the IVF control group
      cleaved at 19-22 hpi. At 24 hpa, the rates of cleavage of oocytes in Group 2
      (52.1%) were greater (P<0.05) than those in Groups 1 and 3 (7 and 38.3%,
      respectively). Only six oocytes (3.3%) in the IVF control group cleaved at 24
      hpi. The overall cleavage rates of oocytes in Group 2 (85.5%) at 48 hpa were
      greater (P<0.05) than other treatments, but it did not show any difference when
      compared with the IVF control group (75.0%). The development rate to two-cell
      stage embryos of Group 2 was consistently greater at all observation points
      followed by Groups 3 and 1. Similar results were obtained in SCNT embryos, but
      the rates of cleavage at 48 hpi and blastocyst development in Group 2 (68.4 and
      16.3%, respectively) did not differ from Group 3 (63.0 and 13.1%, respectively).
      The chromosomal composition in the parthenotes and SCNT embryos differed (P<0.05)
      among treatments. In Groups 1 and 3, greater percentages of haploid parthenotes
      (86 and 71%, respectively) were observed. In contrast, 84% of parthenotes in
      Group 2 had abnormal ploidy (44% polyploid and 40% mixoploid). In the case of
      SCNT embryos, Groups 1 and 3 had greater percentages of diploid chromosomal sets
      (77 and 70%, respectively), whereas 54% in Group 2 were polyploid or mixoploid.
      These results indicate that DMAP treatment after ionomycin greatly increases the
      developmental rates of parthenotes, but did not differ in blastocyst development
      compare with CHX treatment. However, DMAP treatment increased the time-dependent
      cleavage rate to two-cell stage embryos. Further, it greatly enhanced the
      incidence of chromosomal abnormalities in parthenotes and SCNT embryos. Hence, it
      is concluded that CHX combined with ionomycin is more desirable than DMAP for
      oocyte activation during nuclear transfer in cattle.

PMID- 15979831
TI  - New frontiers in proteomics research: a perspective.
AB  - Substantial advances have been made in the fundamental understanding of human
      biology, ranging from DNA structure to identification of diseases associated with
      genetic abnormalities. Genome sequence information is becoming available in
      unprecedented amounts. The absence of a direct functional correlation between
      gene transcripts and their corresponding proteins, however, represents a
      significant roadblock for improving the efficiency of biological discoveries. The
      success of proteomics depends on the ability to identify and analyze protein
      products in a cell or tissue and, this is reliant on the application of several
      key technologies. Proteomics is in its exponential growth phase. Two-dimensional
      electrophoresis complemented with mass spectrometry provides a global view of the
      state of the proteins from the sample. Proteins identification is a requirement
      to understand their functional diversity. Subtle difference in protein structure
      and function can contribute to complexity and diversity of life. This review
      focuses on the progress and the applications of proteomics science with special
      reference to integration of the evolving technologies involved to address
      biological questions.

PMID- 15979832
TI  - Mechanism of permeability-enhancing effect of EDTA and boric acid on the corneal
      penetration of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5
      yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS-088).
AB  - This study was conducted to clarify the penetration properties of 4-[1-hydroxy-1
      methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl]methylimidazole-5
      carboxylic acid monohydrate (CS-088), an ophthalmic agent, and the mechanism of
      the permeability-enhancing effect of EDTA and boric acid (EDTA/boric acid) on the
      corneal penetration of CS-088. In the absence of additives, corneal permeability
      decreased with increasing concentration of CS-088 as CS-088 monomers self
      associate to form dimers. Presence of EDTA/boric acid caused no significant
      changes in the physicochemical properties of CS-088, the apparent partition
      coefficient or the mean particle size of CS-088. EDTA/boric acid induced only a
      slight change in the zeta potential of liposomes used as a model of the
      biological membrane. On the other hand, EDTA/boric acid significantly increased
      membrane fluidity of liposomes, whereas other buffering agents tested did not.
      This effect was synergistic and concentration-dependent for both EDTA and boric
      acid as was observed in in vitro corneal penetration of CS-088. In accordance
      with the result, the rate of CS-088 permeation into the liposomes significantly
      increased by the addition of EDTA/boric acid. Therefore, it was demonstrated that
      EDTA/boric acid promotes corneal penetration of CS-088 through the transcellular
      pathway by increasing membrane fluidity. Conversely, other buffering agents
      decreased corneal permeability of CS-088 by inducing further self-association of
      CS-088 aggregates.

PMID- 15979833
TI  - Clinical parameters, postmortem analysis and estimation of lethal dose in victims
      of a massive intoxication with diethylene glycol.
AB  - This work analyzes a massive intoxication that occurred in 1992 in Argentina as a
      result of the use of propolis syrup as a popular upper respiratory infection
      medicinal agent. The intoxicating agent was diethylene glycol (DEG), which caused
      metabolic acidosis, anuria, renal failure and death in 15 out of the 29 studied
      victims. DEG poisoning cases were classified in three groups according to
      survival time: Group 1-patients that survived up to 3 days; Group 2-patients that
      survived between 4 and 5 days; Group 3-patients that survived between 6 and 21
      days. Patients from Group 1 showed the highest values of anion gap, the lowest
      measures of base excess (BE) and more severe clinical manifestations. Correlation
      between pH and BE was r(2) = 0.68, 0.99 and 0.55 for Groups 1, 2 and 3,
      respectively. A methanolic extraction was performed on the fatal victims' viscera
      and blood, with subsequent concentration and purification. The semi-crystalline
      fraction obtained retained DEG by means of co-dissolution and adsorption as
      demonstrated by thin lay chromatography/flame ionisation detection (TLC/FID). In
      3 out of the 15 fatal cases (from Group 1), DEG was isolated from viscera and
      blood (femoral venous), between 48 and 72 h post ingestion. The concentration
      relation (DEG)viscera/(DEG)blood ranged from 1.45 to 1.55 with a coefficient
      correlation r(2)=0.96 (n=3). In the other victims, DEG could not be detected. The
      reason for this could be the long survival period of the victims after their
      ingestion of the syrup. Additionally, putrefying mechanisms could have been
      operating. Samples of the propolis syrup of each victim were studied by means of
      nuclear magnetic resonance (NMR) and quantified by gas chromatography/flame
      ionisation detection (GC/FID). Results showed that syrup samples contained 65.0%
      (w/v) of diethylene glycol (DEG) and 32.0% (w/v) of propylene glycol (PG). A good
      correlation between the amount of DEG ingested and the anion gap (r(2)=0.63) for
      the 15 victims studied could be observed. The lethal dose for human beings
      estimated in this work ranged from 0.014 to 0.170 mg DEG/kg body weight. This is
      a lower lethal dose than reported in a separate incident in Haiti. These results
      may contribute to the understanding of DEG's metabolic pathway and provides data
      from lethal doses in humans.

PMID- 15979834
TI  - Nonfatal and fatal DOB (2,5-dimethoxy-4-bromoamphetamine) overdose.
AB  - 2,5-Dimethoxy-4-bromoamphetamine (DOB) is a strongly acting hallucinogen with an
      estimated effective dose of 2 mg for an 80 kg man. The case of two men who
      ingested a new "hallucinogen LSD-like" designer drug is reported here. They
      experienced intense hallucinations (onset after 15 min) and vomiting. The men
      became unconscious and fell into deep coma lasting several days. After an unknown
      period of time elapsed they were admitted to a hospital in a comatose state. One
      subject (AX, body mass 113 kg) survived, while the second subject (BX, body mass
      65 kg) experienced convulsions, metabolic acidosis and died 6 days later.
      Gastric, blood, and urine specimens collected on admission into the hospital were
      sent for toxicological examination. Ethanol concentrations in the blood samples
      were less than 0.2 g/kg. CEDIA urine screening indicated the presence of THCOOH
      in both cases, while cocaine and its metabolites were only indicated in the urine
      from AX. Immunoassay for amphetamines was negative in urine specimens collected
      from both subjects. GC-MS analysis for unknown drugs allowed for the discovery of
      the presence of DOB in the gastric and urine samples of both persons. DOB
      targeted analysis for the acetylated analyte confirmed its presence in both
      subjects. Quantitative analysis yielded concentrations in serum of 13 ng/ml (AX)
      and 19 ng/ml (BX). This report on both nonfatal and fatal DOB overdose cases is
      based on clear toxicological evidence, and is the first documentation of DOB
      consumption in the Czech Republic.

PMID- 15979835
TI  - Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma,
      urine and hair. Reference values.
AB  - Four multi-elementary metal and metalloid quantification methods using
      inductively coupled plasma mass spectrometry (ICP-MS) were developed and
      validated in human whole blood, plasma, urine and hair by means of a single
      preparation procedure for each sample. The ICP-MS measurements were performed
      using a Thermo Elemental X7CCT series and PlasmaLab software without a dynamic
      reaction cell. With this procedure 27-32 elements can be simultaneously
      quantified in biological matrices: Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga,
      Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, Pb, Bi, U.
      Whole blood, plasma and urine samples (0.4 ml each) were diluted with purified
      water, acid, triton X100 and butanol. Rhodium was used as internal standard. The
      urine sample results were corrected for enzymatic creatinine determination.
      Twenty-five milligrams hair samples were acid mineralized after a decontamination
      procedure and diluted as previously described for biological fluids. To be
      validated, each element had to show linearity with a correlation coefficient
      higher than 0.99. The intra-assay and inter-assay inaccuracy, measured as the
      variation coefficient, were below 5 and 10% respectively. Global performance was
      assessed by a quality control program. Our laboratory is a registered participant
      of the Institut National de Sante Publique du Quebec (Sainte-Foy, Canada) inter
      laboratory comparison program for whole blood, urine, and beard hair of non
      occupationally exposed individuals spiked with selected elements. In our study
      multi-element metal and metalloid analysis was assessed for 27 elements in whole
      blood, 27 elements in plasma, 30 elements in urine and 32 elements in hair, from
      0 to 25, or 250 to 1000 ng/ml, depending on the element. Quantification limits
      ranged from 0.002 ng/ml (U) to 8.1 ng/ml (Al) for whole blood, from 0.002 ng/ml
      (U) to 7.7 ng/ml (Al) for plasma, from 0.001 ng/ml (U) to 2.2 ng/ml (Se) for
      urine, and from 0.2 pg/mg (Tl) to 0.5 ng/mg (B) for hair. Normal values were
      determined in whole blood (n=100), plasma (n=100), urine (n=100), and hair (n=45)
      of healthy volunteers, leading to approximately 10,000 analyses. All results are
      presented and discussed. Clinical toxicology and forensic toxicology applications
      are also reported. ICP-MS has made significant advances in the field of clinical
      biology, particularly in toxicological analysis. This is due to the use of
      extremely effective equipment that permits better clinical and forensic
      toxicological analysis of metal and metalloid status of each individual patient.

PMID- 15979836
TI  - Electrochemical characteristics of zafirlukast and its determination in
      pharmaceutical formulations by voltammetric methods.
AB  - Simple, rapid, reliable and fully validated voltammetric methods were developed
      for the determination of zafirlukast in pharmaceutical formulations, based on its
      electrochemical reduction at a hanging mercury drop electrode. Its
      electrochemical behavior in borate buffer (pH 8.0) was investigated using cyclic
      voltammetry, linear sweep voltammetry and chronoamperometry. The linear sweep
      voltammetric study of zafirlukast was carried out using glassy carbon electrode.
      A well-defined cathodic peak at -1326 mV without the adsorptive accumulation time
      and at -1312 mV with 20 s of accumulation time versus Ag/AgCl reference electrode
      in square-wave and square-wave adsorptive stripping voltammetric methods,
      respectively, was observed. The experimental and instrumental parameters
      affecting the peak current of zafirlukast were investigated and optimized for the
      zafirlukast determination. The detection limits of square-wave and square-wave
      adsorptive stripping voltammetric methods were 50 and 5 ngmL(-1) with R.S.D. of
      6.79 and 5.72%, respectively. The methods showed good sensitivity, accuracy,
      precision, selectivity, robustness and ruggedness. The proposed methods were
      applied for the determination of zafirlukast in its pharmaceutical formulations.
      The results obtained from developed methods were compared with a
      spectrophotometric method reported in the literature and no significant
      difference was found statistically.

PMID- 15979837
TI  - COX2 expression, angiogenesis, proliferation and survival in Barrett's cancer.
AB  - OBJECTIVES: To examine COX2 expression and its relation to angiogenesis, Ki67 and
      Bcl2 expression in Barrett's cancer. METHODS: Specimens from 48 R0-resected
      Barrett's adenocarcinoma were immunostained for cyclooxygenase 2 (COX2), CD 31
      and alpha-sm actin to discriminate between mature and immature vessels, Mib-1 and
      Bcl2. COX2 staining, angiogenesis, Ki67 expression and Bcl2 expression were also
      measured. RESULTS: COX2 expression was increased in 25 of 48 cases. There was no
      significant correlation between COX2 expression and age, sex and tumor
      differentiation. A significant association was found between lymph node positive
      cases and elevated COX2 expression (p=0.008). The percentage of Ki67 positive
      cancer cells was 43.8% (range 15.4-67.5%) in the low COX2 group and 57.8% (range
      12.0-84.6%) in the high COX2 group. The difference was statistically significant
      (p=0.046). The median neovascularisation coefficient in the low COX2 group was
      11.68 (range 8.22-43.64) and 25.47 (range 8-38.3) in the high COX2 group. The
      difference was statistically significant (p=0.012). A significant difference in
      survival was observed between patients in the COX2 low category when compared
      with the COX2 high category (log-rank test p=0.013). CONCLUSIONS: Elevated COX2
      expression is associated with lymph-node metastases and reduced survival in
      Barrett's cancer. This appears to be related to the induction of angiogenesis and
      proliferation.

PMID- 15979838
TI  - Simple versus complex PTSD: a cluster analytic investigation.
AB  - A cluster analytic investigation was conducted on measures of PTSD associated
      features (e.g., personality pathology, dissociative tendencies) to investigate
      whether empirically-defined clusters correspond to Herman's [1992, Complex PTSD:
      a syndrome in survivors of prolonged and repeated trauma. Journal of Traumatic
      Stress, 5, 377-391; 1997, Trauma and recovery (Rev. ed.). New York: Basic Books]
      distinction between simple and complex PTSD. Results from a sample of 60 PTSD
      patients were broadly consistent with this distinction, although some
      inconsistencies were observed. Treatment outcome generally did not differ between
      the two clusters. Implications for classifying and treating PTSD are discussed.

PMID- 15979839
TI  - Relative efficiency of the linkage disequilibrium mapping approach in detecting
      candidate genes for schizophrenia in different European populations.
AB  - Detection of susceptibility genes in indirect association studies depends not
      only on the degree of linkage disequilibrium between the disease variant and the
      SNP marker but also on the difference in their allele frequencies. Little is
      known about how variations in these parameters may affect the power of indirect
      association studies among related populations. Toward this goal, we genotyped 40
      SNPs at four loci in samples from three European populations, Galician, Greek,
      and Norwegian. We compared the relative efficiency of all pairs of SNPs in
      detecting each other in each one of the populations. Our results show that a low
      percentage of marker SNPs may detect association in some populations but be
      totally ineffective in others. Therefore, these differences have to be an
      additional factor to consider when a replication study fails to confirm initial
      associations, especially if the replication is focused on very few markers.

PMID- 15979840
TI  - Detection of potential GDF6 regulatory elements by multispecies sequence
      comparisons and identification of a skeletal joint enhancer.
AB  - The identification of noncoding functional elements within vertebrate genomes,
      such as those that regulate gene expression, is a major challenge. Comparisons of
      orthologous sequences from multiple species are effective at detecting highly
      conserved regions and can reveal potential regulatory sequences. The GDF6 gene
      controls developmental patterning of skeletal joints and is associated with
      numerous, distant cis-acting regulatory elements. Using sequence data from 14
      vertebrate species, we performed novel multispecies comparative analyses to
      detect highly conserved sequences flanking GDF6. The complementary tools WebMCS
      and ExactPlus identified a series of multispecies conserved sequences (MCSs). Of
      particular interest are MCSs within noncoding regions previously shown to contain
      GDF6 regulatory elements. A previously reported conserved sequence at -64 kb was
      also detected by both WebMCS and ExactPlus. Analysis of LacZ-reporter transgenic
      mice revealed that a 440-bp segment from this region contains an enhancer for
      Gdf6 expression in developing proximal limb joints. Several other MCSs represent
      candidate GDF6 regulatory elements; many of these are not conserved in fish or
      frog, but are strongly conserved in mammals.

PMID- 15979842
TI  - Professional caretakers as attachment figures in day care centers for children
      with intellectual disability and behavior problems.
AB  - Do children with intellectual disabilities (ID) show attachment behavior towards
      their professional caretaker? Five children, varying in chronological age,
      developmental age and DSM-diagnosis, were observed in a day care setting. Their
      attachment behavior was described by means of the Attachment Q-sort. Attachment
      behavior varied within and between children, irrespective of their diagnosis.
      This data indicates that professional caretakers are potential attachment figures
      for children with ID. Attachment introduces certain considerations for day care
      for children with ID, as well as opportunities for prevention and intervention.
      Implications for research and practice are discussed.

PMID- 15979841
TI  - Protective role of lycopene on cisplatin-induced changes in sperm
      characteristics, testicular damage and oxidative stress in rats.
AB  - The aim of this study was to investigate the possible protective role of lycopene
      on cisplatin (CP)-induced spermiotoxicity using quantitative, biochemical and
      histopathological approaches. Adult male Sprague-Dawley rats were randomly
      divided into four groups. The control group received physiological saline;
      animals in cisplatin group received only cisplatin; pre-treatment group received
      a 10-day of lycopene before administration of cisplatin while animals in post
      treatment group received a 5-day of lycopene following administration of
      cisplatin. Cisplatin (7 mg kg(-1)) was intraperitoneally (i.p.) injected as a
      single dose and lycopene (4 mg kg(-1)) was administered by gavage in corn oil.
      Traits of reproductive organs; sperm characteristics, testicular histological
      findings, plasma testosterone levels and the testicular tissue oxidative status
      were determined. Administration of cisplatin to rats decreased sperm
      concentration (p < 0.05) and sperm motility (p < 0.001), increased total abnormal
      sperm rates (p < 0.05) as compared with the control group. While a marked
      normalization was achieved only in sperm concentration with lycopene in pre
      treatment group, significant normalizations were achieved in the sperm
      concentration, sperm motility, total abnormal sperm rates in post-treatment
      group. No significant differences in levels of testosterone were observed among
      all groups. An increase in testes malondialdehyde concentrations (p < 0.05) and
      glutathione peroxidase activities (p < 0.001) were detected while significant
      decreases in glutathione levels (p < 0.001) in cisplatin alone group when
      compared to control group. While pre-treatment with lycopene restoring only
      malondialdehyde concentrations, its post-treatment caused normalization in both
      malondialdehyde and glutathione levels when compared with the cisplatin alone
      group. On the other hand, significant increases were determined in GSH-Px
      activities in all experimental groups when compared with the control group.
      Although the mechanism is not clear, the results from this experimental study
      suggest that the lycopene have a possible protective effect against cisplatin
      induced spermiotoxicity, effect of giving lycopene after cisplatin being superior
      to the giving it before cisplatin.

PMID- 15979843
TI  - Behavioral assessment of joint attention: a methodological report.
AB  - This paper describes a highly structured assessment protocol with objective
      behavioral measures for joint attention responding and initiation. The assessment
      was given to 26 children diagnosed with autism spectrum disorders and 21
      typically developing children, aged two to four years. Interobserver agreement
      was high for all behavioral measures. Children with autism had relatively minor
      deficits in joint attention responding and more severe deficits in joint
      attention initiation, relative to typically developing children. These results
      replicate those reported in previous research. The protocol can be used reliably
      to assess behavior indicative of joint attention responding and initiation in
      typically developing children and children with autism.

PMID- 15979844
TI  - Techniques for efficient, real-time, 3D visualization of multi-modality cardiac
      data using consumer graphics hardware.
AB  - We exploit consumer graphics hardware to perform real-time processing and
      visualization of high-resolution, 4D cardiac data. We have implemented real-time,
      realistic volume rendering, interactive 4D motion segmentation of cardiac data,
      visualization of multi-modality cardiac data and 3D display of multiple series
      cardiac MRI. We show that an ATI Radeon 9700 Pro can render a 512x512x128 cardiac
      Computed Tomography (CT) study at 0.9 to 60 frames per second (fps) depending on
      rendering parameters and that 4D motion based segmentation can be performed in
      real-time. We conclude that real-time rendering and processing of cardiac data
      can be implemented on consumer graphics cards.

PMID- 15979845
TI  - Cooperation of H2O2-mediated ERK activation with Smad pathway in TGF-beta1
      induction of p21WAF1/Cip1.
AB  - Although it has been demonstrated that p21WAF1/Cip1 could be induced by
      transforming growth factor-beta1 (TGF-beta1) in a Smad-dependent manner, the
      cross-talk of Smad signaling pathway with other signaling pathways still remains
      poorly understood. In this study, we investigated a possible role of hydrogen
      peroxide (H2O2)-ERK pathway in TGF-beta1 induction of p21WAF1/Cip1 in human
      keratinocytes HaCaT cells. Using pharmacological inhibitors specific for MAP
      kinase family members, we found that ERK, but not JNK or p38, is required for TGF
      beta1 induction of p21WAF1/Cip1. ERK activation by TGF-beta1 was significantly
      attenuated by treatment with N-acetyl-l-cysteine or catalase, indicating that
      reactive oxygen species (ROS) generated by TGF-beta1, mainly H2O2, stimulates ERK
      signaling pathway to induce the p21WAF1/Cip1 expression. In support of this, TGF
      beta1 stimulation caused an increase in intracellular ROS level, which was
      completely abolished by pretreatment with catalase. ERK activation does not
      appear to be associated with nuclear translocation of Smad-3, because ERK
      inhibition did not affect nuclear translocation of Smads by TGF-beta1, and H2O2
      treatment alone did not cause nuclear translocation of Smad-3. On the other hand,
      ERK inhibition ablated the phosphorylation of Sp1 by TGF-beta1, which was
      accompanied with the disruption of interaction between Smad-3 and Sp1 as well as
      of the recruitment of Sp1 to the p21WAF1/Cip1 promoter induced by TGF-beta1,
      indicating that ERK signaling pathway might be necessary for their interaction.
      Taken together, these results suggest that activation of H2O2-mediated ERK
      signaling pathway is required for p21WAF1/Cip1 expression by TGF-beta1 and led us
      to propose a cooperative model whereby TGF-beta1-induced receptor activation
      stimulates not only a Smad pathway but also a parallel H2O2-mediated ERK pathway
      that acts as a key determinant for association between Smads and Sp1
      transcription factor.

PMID- 15979846
TI  - Prostacyclin receptor induces STAT1 and STAT3 phosphorylations in human
      erythroleukemia cells: a mechanism requiring PTX-insensitive G proteins, ERK and
      JNK.
AB  - The ability of the human prostacyclin receptor (hIP) to regulate the activities
      of signal transducers and activators of transcription (STATs) has not yet been
      documented. In the present study, we have delineated the mechanism by which hIP
      induces STAT3 phosphorylations in human erythroleukemia (HEL) cells. Stimulation
      of endogenous hIP by its specific agonist, cicaprost, resulted in STAT3 Tyr705
      and Ser727 phosphorylations in a time- and concentration-dependent manner.
      Cicaprost-induced STAT3 Tyr705 and Ser727 phosphorylations were resistant to
      pertussis toxin (PTX) treatment, suggesting that these responses were mediated
      through PTX-insensitive G proteins. In addition, extracellular signal-regulated
      kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 MAPK, were shown to
      be phosphorylated by cicaprost in a time- and concentration-dependent manner via
      PTX-insensitive G proteins. The levels of the interaction between STAT3, ERK and
      JNK were enhanced by cicaprost treatment. The involvement of Raf-1, MEK1/2 and
      JNK in cicaprost-induced phosphorylations of STAT3 was illustrated by the use of
      their selective inhibitors. In contrast, p38 MAPK did not appear to be required.
      Similar observations were obtained with STAT1 upon stimulation by cicaprost.
      Taken together, these results demonstrate for the first time that hIP activation
      by cicaprost can lead to STAT1 and STAT3 phosphorylations via signaling pathways
      involving PTX-insensitive G proteins, ERK and JNK.

PMID- 15979849
TI  - Tooth transplantations: a descriptive retrospective study.
AB  - The aim of the present study was to perform a retrospective study of
      autogeneously transplanted teeth in order to examine the influence of clinical
      criteria such as the type of the donor tooth, the root length at the time of
      transplantation, donor eruption stage and others on the overall success rate of
      the transplantation. The material of this study consisted of 194 patients in whom
      273 teeth were transplanted. The mean age at the time of autotransplantation was
      18.1 years with a standard deviation of 7.5 years. Transplantations were
      performed in two hospitals. The follow-up period varied from 15 days to 11 years,
      and the mean follow-up time was 3.8 years. 58/273 teeth showed one or other form
      of resorption, 37/273 teeth showed ankylosis, 30/273 showed no important changes
      in pulp chamber size, 104/273 showed major discoloration after transplantation,
      92/273 teeth showed positive results for cold test after transplantation and
      26/273 teeth showed clinically unacceptable pocket depth. Clinical and
      radiological evaluations were performed. An association was found between
      successful transplantation and donor tooth type (P<0.01), root length at the time
      of transplantation (P<0.0001) and recipient tooth site (P=0.03). There was a
      borderline association between successful transplantation and donor eruption
      stage (P=0.05). In conclusion, autotransplantation of teeth performed with a
      careful surgical procedure at the stage of 1/2-3/4 of their intended or expected
      root length can render a very useful service to patients.

PMID- 15979848
TI  - Essential role of the LIM domain in the formation of the PKCepsilon-ENH-N-type
      Ca2+ channel complex.
AB  - A LIM domain is a specialized double-zinc finger motif found in a variety of
      proteins. LIM domains are thought to function as molecular modules, mediating
      specific protein-protein interactions in cellular signaling. In a recent study,
      we have demonstrated that ENH, which has three consecutive LIM domains, acts as
      an adaptor protein for the formation of a functional PKCepsilon-ENH-N-type Ca2+
      channel complex in neurons. Formation of this complex selectively recruits
      PKCepsilon to its specific substrate, N-type Ca2+ channels, and is critical for
      rapid and efficient potentiation of the Ca2+ channel activity by PKC in neurons.
      However, it is not clear whether changes in the local Ca2+ concentrations near
      the channel mouth may affect the formation of the triprotein complex.
      Furthermore, the molecular determinants for the interactions among these three
      proteins remain unknown. Biochemical studies were performed to address these
      questions. Within the physiological Ca2+ concentration range (0-300 microM),
      binding of ENH to the channel C-terminus was significantly increased by Ca2+,
      whereas increased Ca2+ levels led to dissociation of PKCepsilon from ENH.
      Mutagenesis studies revealed that the second LIM domain in ENH was primarily
      responsible for Ca2+-dependent binding of ENH to both the Ca2+ channel C-terminus
      and PKCepsilon. ENH existed as a dimer in vivo. PKCepsilon translocation
      inhibition peptide, which blocks the translocation of PKCepsilon from the cytosol
      to the membrane, inhibited the interaction between PKCepsilon and ENH. These
      results provide a molecular mechanism for how the PKCepsilon-ENH-N-type Ca2+
      channel complex is formed and regulated, as well as potential drug targets to
      selectively disrupt the PKC signaling complex.

PMID- 15979847
TI  - Mitogen-activated protein kinase (MAPK)-docking sites in MAPK kinases function as
      tethers that are crucial for MAPK regulation in vivo.
AB  - Docking sites on targets of mitogen-activated protein kinases (MAPKs) facilitate
      accurate and efficient substrate phosphorylation. MAPK/ERK kinases (MEKs, or
      MKKs), the upstream regulators of MAPKs, also contain N-terminal MAPK-docking
      sites, or 'D-sites'; however, the in vivo functions of MEK D-sites are
      incompletely understood. Here we found that the ability of constitutively-active
      human MEK1 and MEK2 to stimulate ERK phosphorylation and to induce the neoplastic
      transformation of NIH 3T3 cells required the integrity of the D-site. In
      addition, D-site mutants of otherwise wild-type MEK1/2 were unable to anchor
      unphosphorylated ERK2 in the cytoplasm. ERK activation, cytoplasmic anchoring and
      release were completely retained in 'swap' mutants in which MEK2's D-site was
      replaced with the D-site of MEK1 or yeast Ste7. Furthermore, these abilities were
      significantly retained when MEK2's D-site was moved to its C-terminus, or
      replaced by an unrelated MAPK-binding domain taken from the Ets-1 transcription
      factor. We conclude that the D-sites in MEKs are crucial for the activation of
      their cognate MAPKs in vivo, and that their primary function is to tether their
      cognate MAPKs near the MEK's kinase domain. This proximity effect is sufficient
      to explain the contribution that the D-site interaction makes to several
      biologically important signaling events.

PMID- 15979850
TI  - Healing following tooth extraction in cyclosporine-fed rats.
AB  - Healing after tooth extraction was studied in rats treated with cyclosporine-A
      (CSA) for four weeks. Sixty male Sprague-Dawley rats were assigned to one of
      three groups of 20 rats each. The maxillary right molars were extracted from two
      groups; the third group served as a non-extraction control. The non-extraction
      group and one extraction group (vehicle control) received the solvent mineral oil
      daily, and the other extraction group received 15 mg/kg CSA in mineral oil. Five
      rats from each group were killed 5, 10, 14 and 28 days after extraction and
      samples analyzed histologically. On days 5 and 10, bone volume was significantly
      lower and marrow volume significantly higher in both extraction groups than in
      the non-extraction group. The fractional-formation surfaces were significantly
      lower in the extraction groups than in the non-extraction group on day 5 only.
      Osteoid volume was significantly higher in the extraction vehicle control group
      than in the other two groups on days 10 and 14; however, the osteoid volume was
      higher in the CSA group than in the other two groups on day 28. On days 14 and
      28, bone volume was lower and marrow volume higher in the CSA group than in the
      extraction vehicle control and non-extraction groups. On day 28, bony surface
      areas were significantly greater in the CSA group than in the extraction vehicle
      control and non-extraction groups. Soft-tissue evaluation showed significantly
      greater epithelial areas, connective tissue areas and total tissue areas in the
      CSA group than in the extraction vehicle control group on day 28, but not on day
      14. These data suggest that CSA may influence healing of both the gingival tissue
      and the alveolar bony sockets in the tooth-extraction wound. Further detailed
      study is needed to identify the mechanisms responsible.

PMID- 15979852
TI  - Magnetic resonance arthrography applied to the diagnosis of intraarticular
      adhesions of the temporomandibular joint.
AB  - The purpose of this study is to investigate the diagnostic accuracy of magnetic
      resonance arthrography (MRAr) on the diagnosis of intraarticular adhesions of the
      temporomandibular joint (TMJ). Twenty-four patients (31 joints) diagnosed as
      internal disorders of TMJ were examined to establish the presence, suspicion or
      absence of intraarticular adhesions through MRAr according to the MRAr
      radiographic criteria in a blind fashion, subsequent arthroscopy were performed
      on all 31 joints. The findings were compared to MRAr with those of arthroscopy.
      The comparison data were assessed by generating receiver operating characteristic
      curve (ROC curve) and analyzing the area (Az) under the curve with SPSS11.0
      software. The area under the ROC curve was 0.91 (0.86, 0.95), P<0.05. MRAr proves
      to be an excellent modality to diagnose intraarticular adhesions of TMJ.

PMID- 15979851
TI  - Prospective evaluation of a pragmatic treatment rationale: open reduction and
      internal fixation of displaced and dislocated condyle and condylar head fractures
      and closed reduction of non-displaced, non-dislocated fractures. Part I: condyle
      and subcondylar fractures.
AB  - This prospective study evaluated outcomes of closed reduction (CR) in non
      displaced, non-dislocated condyle and subcondylar fractures (Class I) and open
      reduction and internal fixation (ORIF) of displaced (Class II) and dislocated
      (Class IV) fractures. Forty-five patients with 51 fractures (six (13%) with
      bilateral fractures), 11 (25%) CR and 34 (75%) ORIF, were enrolled in a 1-year
      follow up that 20 patients with 25 fractures completed. Condylar translation in
      Class I fractures recovered to 12mm for vertical opening, 9mm for protrusion, 8mm
      for mediotrusion; in Class II, respectively, 10, 7 and 9mm; and Class IV,
      respectively, 8, 7 and 7mm. Incisal movements recovered to 46, 8 and 9mm in Class
      I; 44, 7 and 9mm in Class II; and 43, 5 and 7mm in Class IV. Vertical and angular
      fragment reduction versus the non-fractured condyle was +0.3 to -1.9mm, +1.1
      degrees to +1.8 degrees in Class I; -2.2 to -1.9mm, +0.6 degrees to -1.2 degrees
      in Class II; +2.9 to -1.1mm, +18.4 degrees to +6 degrees in Class IV.
      Malocclusion and joint locking were unreliable determinants for a treatment
      decision, being forged by concomitant fractures. All complications subsided after
      6 months; translation and incisal movements returned to within the normal range
      in proportion to the severity of displacement and dislocation. Vertical opening
      translation in Class IV fractures remained short-to-normal and was compensated by
      rotation. Unacceptable clinical function according to predefined standards was
      not found after 1 year. Angular reposition was better than vertical reduction.
      This study documents successful evidence-based treatment according to predefined
      criteria.

PMID- 15979853
TI  - Biodegradable polydioxanone and poly(l/d)lactide implants: an experimental study
      on peri-implant tissue response.
AB  - Several implants for orbital wall fracture treatment are available at the
      present, but they have drawbacks: resorption, risk for migration and foreign body
      reaction. Alloplastic resorbable implants would be advantageous: no removal
      operation and no donor side morbidity. The purpose of this study was to evaluate
      the foreign body reaction, capsule formation and mechanical properties of two
      bioresorbable implants. PDS and SR-P(L/DL)LA mesh sheet (70/30) with solid frame
      (96/4) implants (SR-P(L/DL)LA 70,96) were placed into subcutaneous tissue of 24
      rats. Immunohistochemistry was used to evaluate reactivity for Tn-C, alpha-actin,
      type I and III collagens and two mononuclear cells: T-cells and monocyte/
      macrophage. GPC, DSC and SEM were performed. Student's t-test or nonparametric
      Kruskall-Wallis test were used for statistical analysis. Histology of peri
      implant capsule exhibited an inner cell-rich zone and an outer connective tissue
      zone around both materials. Tn-C reactivity was high in the inner and alpha-actin
      in the outer zone. At the end of the study, the difference of type I collagen
      versus type III collagen reactivity in inner zone was statistically significant
      (P<0.0001) as was the difference of type I collagen versus type III collagen
      reactivity in outer zone (P<0.0001). Immunohistochemistry did not reveal any
      statistical differences of T-cell and monocyte/macrophage reactivity around PDS
      versus SR-P(L/DL)LA 70,96 implants, nor any differences as a function of time.
      PDS were deformed totally after 2 months. SR-P(L/DL)LA 70,96 implants were only
      slightly deformed during the follow up of 7 months. PDS degraded rapidly in SEM
      observation. Particles were detaching from surface. SEM observation revealed that
      polylactide implant was degrading from the surface and the inner porous core
      became visible. The degradation came visible at 7 months. There were cracks in
      perpendicular direction towards to the long axis of the filaments. M(w) of PDS
      decreased fast compared to the polylactide implant. Foreign body reaction was
      minimal to both materials but continued throughout the whole observation period.
      Mechanically PDS was poor, it looses its shape totally within 2 months. It cannot
      be recommended for orbital wall reconstruction. New mesh sheet-frame structure
      (SR-P(L/DL)LA 70,96) approved to be mechanically adequate for orbital wall
      reconstruction. It seems not to possess intrinsic memory and retains its shape.
      The resorption time is significantly longer compared to PDS and is comparable to
      other studied P(L/DL)LA copolymers. Thus, the new polylactide copolymer implant
      may support the orbital contents long enough to give way to bone growth over the
      wall defect.

PMID- 15979854
TI  - Effects of ryanodine receptor activation on neurotransmitter release and neuronal
      cell death following kainic acid-induced status epilepticus.
AB  - Dynamic changes in intracellular free Ca(2+) concentration play a crucial role in
      various neural functions. The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)
      and the ryanodine (Ry) receptor (RyR) are involved in Ca(2+)-induced Ca(2+)
      release (CICR). Recent studies have shown that type 3 IP3R is highly expressed in
      rat hippocampal neurons after kainic acid (KA)-induced seizures and that
      dantrolene, a RyR antagonist, reduces KA-induced neuronal cell death. We
      investigated the RyR-associated effects of CICR agents on basal and K(+)-evoked
      releases of GABA and glutamate in rat hippocampus and the changes in expression
      of mRNA for RyRs in mouse brain after KA-induced seizures. The stimulatory effect
      of Ry on releases of GABA and glutamate was concentration-dependent in a biphasic
      manner. The inflection point in concentration-response curves for Ry on GABA
      release was lower than that for glutamate in both basal and K(+)-evoked
      conditions, suggesting that hyperactivation of RyR-associated CICR produces the
      imbalance between GABAergic and glutamatergic transmission. Following KA-induced
      seizures, transient up-regulation of brain-type RyR mRNA was observed in the
      hippocampal CA3 region and striatum, and signals for c-Fos mRNA increased
      transiently in the hippocampus, dentate gyrus and deeper layers of the neocortex.
      Thereafter, some dead neurons with single-stranded DNA (ssDNA) immunoreactive
      fragmented nuclei appeared in these areas. These findings suggest that
      intracellular Ca(2+) release via the RyR might be one of the mechanisms involved
      in KA-induced neuronal cell death.

PMID- 15979855
TI  - Mechanisms contributing to the exacerbated epileptiform activity in hippocampal
      slices expressing a C-terminal truncated GABA(B2) receptor subunit.
AB  - GABAergic synaptic transmission plays an important role in the patterning of
      epileptiform activity. We have previously shown that global loss of GABA(B)
      receptor function due to transgenic deletion of the GABA(B1) receptor subunit
      exacerbates epileptiform activity induced by pharmacological manipulations in
      hippocampal slices. Here we show that a similar hyperexcitable phenotype is
      observed in hippocampal slices prepared from a transgenic mouse expressing a
      GABA(B2) receptor subunit lacking its C terminal tail (the DeltaGB2-Ct mouse); a
      molecular manipulation that also produces complete loss of GABA(B) receptor
      function. Thus, epileptiform bursts that are sensitive to NMDA receptor
      antagonists (induced by either the GABA(A) receptor antagonist bicuculline
      (10muM) or removal of extracellular Mg(2+)) were significantly longer in duration
      in DeltaGB2-Ct slices relative to WT slices. We now extend these observations to
      demonstrate that a stimulus train induced bursting (STIB) protocol also evokes
      significantly longer bicuculline sensitive bursts of activity in DeltaGB2-Ct
      slices compared to WT. Furthermore, synchronous GABA(A) receptor-mediated
      potentials recorded in the presence of the potassium channel blocker 4
      aminopyridine (4-AP, 100muM) and the ionotropic glutamate receptor antagonists
      NBQX (20muM) and D-AP5 (50muM) were significantly prolonged in duration in
      DeltaGB2-Ct versus WT slices. These data suggest that the loss of GABA(B)
      receptor function in DeltaGB2-Ct hippocampal slices promotes depolarising GABA(A)
      receptor-mediated events, which in turn, leads to the generation of ictal-like
      events, which may contribute to the epilepsy phenotype observed in vivo.

PMID- 15979856
TI  - Relationship between constitutive nuclear factor-kappaB (NF-kappaB) and inhibitor
      kappaB-alpha (IkappaB-alpha) in an interferon-alpha-sensitive human Burkitt
      lymphoma cell line.
AB  - The human Burkitt lymphoma Daudi cell line expresses constitutively active
      nuclear factor kappaB (NF-kappaB) in the nucleus in spite of high levels of
      inhibitor kappaB-alpha (IkappaB-alpha) in the cytoplasm. The antiproliferative
      response of these cells to interferon-alpha (IFN-alpha) correlated with the
      inhibition of the constitutive NF-kappaB activity by the cytokine. The present
      study shows that IFN-alpha caused an increase in p53 level, inhibited cell
      proliferation by [(3)H]thymidine incorporation, and stimulated cytotoxicity and
      apoptosis by PARP-cleavage in the Daudi cells. In order to study the relationship
      between the constitutively active NF-kappaB and IkappaB-alpha, a dominant
      negative mutant IkappaB-alpha (IkappaB-alphaDN), lacking the N-terminal 36 amino
      acids required for the activation of NF-kappaB by tumor necrosis factor-alpha
      (TNF-alpha), was expressed in the Daudi cells. The expression of IkappaB-alphaDN
      protein did not inhibit the constitutive NF-kappaB activity, but it inhibited
      cell proliferation, antiproliferative response to IFN-alpha, and phosphorylated
      mitogen activated protein kinase (p-MAPK) level. Thus, our results suggest that
      constitutive NF-kappaB activity in the human Burkitt lymphoma Daudi cells is
      maintained by a mechanism independent of IkappaB-alpha degradation, and that the
      IkappaB-alpha is involved in the proliferation of these cells, possibly through
      the MAP kinase pathway. Therefore, in addition to IFN-alpha treatment, both NF
      kappaB and IkappaB-alpha may be used as drug targets for inhibiting cell
      proliferation in the lymphomas.

PMID- 15979857
TI  - Effects of glucose and mannose on the flocculation behavior of Saccharomyces
      cerevisiae at different life stages.
AB  - The temporal flocculation behavior of Saccharomyces cerevisiae at different life
      stages is investigated using glucose and mannose as the different carbon sources,
      and the temporal variations of cell size, zeta potential and stability ratio of
      cell suspension are measured. It is found that the largest cell size and the
      lowest stability ratio of cell suspension occurred at the middle period of the
      exponential growth phase independent of carbon sources. The colloidal aspect was
      analyzed by using the DLVO theory, and indicated that the gravitational force
      plays a major role in determining the flocculation behavior of yeast cells.

PMID- 15979858
TI  - New protocols for preparing dipalmitoylphosphatidylcholine dispersions and
      controlling surface tension and competitive adsorption with albumin at the
      air/aqueous interface.
AB  - The adsorption behavior of dipalmitoylphosphatidylcholine (DPPC), which is the
      major component of lung surfactant, at the air/aqueous interface and the
      competitive adsorption with bovine serum albumin (BSA) were studied with
      tensiometry, infrared reflection absorption spectroscopy (IRRAS), and
      ellipsometry. Dynamic surface tensions lower than 1 mN/m were observed for DPPC
      dispersions, with mostly vesicles, prepared with new protocols, involving
      extensive sonication above 50 degrees C. The lipid adsorbs faster and more
      extensively for DPPC dispersions with vesicles than with liposomes. For DPPC
      dispersions by a certain preparation procedure at T>T(c), when lipid particles
      were observed on the surface, dynamic surface tensions as low as 1 mN/m were
      measured. Moreover, IRRAS intensities and ellipsometric deltaDelta values were
      found to be much higher than the values for other DPPC dispersions or spread DPPC
      monolayers, suggesting that a larger amount of liposomes or vesicles adsorb on
      the surface. For DPPC/BSA mixtures, the tension behavior is controlled primarily
      by BSA, which prevents the formation of a dense DPPC monolayer. When BSA is
      injected into the subphase with a spread DPPC monolayer or into a DPPC dispersion
      with preadsorbed layers, little or no BSA adsorbs and the DPPC layer remains on
      the surface. When a DPPC monolayer is spread on a BSA solution at 0.1 wt% at 25
      degrees C, then DPPC lipid can displace the adsorbed BSA molecules. The lack of
      BSA adsorption, and the expulsion of BSA by DPPC monolayer is probably due to the
      strong hydrophilicity of the lipid polar headgroup. When a DPPC dispersion is
      introduced with Trurnit's method or when dispersion drops are sprayed onto the
      surface of a DPPC/BSA mixture, the surface tension becomes lower and is
      controlled by DPPC, which can prevent the adsorption of BSA. The results may be
      important in understanding inhibition of lung surfactants by serum proteins and
      in designing efficient protocols of surfactant preparation and administration.

PMID- 15979859
TI  - Protoplast isolation of callus in Echinacea augustifolia.
AB  - Preparations from Echinacea are among the most widely used herbal medicines. Most
      uses of Echinacea are based on the reported immunological properties. In this
      paper, we used callus of Echinacea augustifolia for isolation and researched the
      factors influencing the process of protoplasts preparation, the result indicated
      it was easy to isolate protoplast from buff-green Callus in E. augustifolia which
      was looked like granule with symmetrical character. The result showed that the
      best enzyme solution concentration is composed of cellulase 2.0% (w/v),
      pectinase1.0% (w/v), hemicellulase 0.5% (w/v), 0.7 mol/L mannitol and 50.0 x
      10(4) gFW(-1) protoplasts were obtained after 8 h later. The yield of protoplasts
      was significantly influenced by cellulase concentration and incubation time.
      Finally, we summarized an integrated approach including callus induction, callus
      culture, isolation, purification, identification and calculation of protoplasts.

PMID- 15979860
TI  - [Phimosis: medical treatment or circumcision?].
AB  - Phimosis remains a major question for mothers and induces a high number of
      consultations. However, large epidemiologic series have shown that congenital
      phimosis may disappear spontaneously in around 80% of cases with development and
      should'nt need any treatment before the age of five or six years old. Theses
      elements go against sociocultural habits which induce many circumcisions before
      the age of six. Corticoid treatment of phimosis seems to be very efficient to
      facilitate the disparition of phimosis. The aim of this literature review is to
      evaluate medical, socioeconomical and therapeutics aspects of phimosis. Based on
      these data, we recommend never to treat phimosis before the age of one year old,
      to wait as long as possible for spontaneous evolution of phimosis until the age
      of five years old, and, in case of non evolution of congenital phimosis or
      pathologic phimosis to use as first step treatment corticoid topics rather than
      surgical treatment.

PMID- 15979861
TI  - [Food avoidance emotional disorder in 3 to 10-year-old children: a clinical
      reality].
AB  - We underline the clinical importance of a specific eating disorder in 3 to 10
      years old children, when the majority of the works about the prepubertal eating
      disorders focus either on the period just preceding adolescence (often between 10
      and 13 years), or on the second half of the first year of the baby. Within the
      eating disorders described in the literature, we compare the clinical
      presentation of most of these 3 to 10 years old children with the food avoidance
      emotional disorder described during adolescence. These problems of eating
      behaviour (various selective eating with or without provoked vomiting) are
      ignored for a long time in these young children because of quite a satisfactory
      growth, but these children are often seen in emergency rooms because of a
      brutally complete eating refusal. Therapeutic consultations allow these children
      to express their fears about diseases, poisoning and death, for themselves or for
      their close relations, in particular the mother, without endangering their body.
      The early recognition and care of these difficulties of conciliation between the
      body and the thoughts impose a narrow collaboration between paediatric and
      psychiatric staffs.

PMID- 15979862
TI  - [The << king-child >>: a modern pathology? Sociopsychological thoughts and
      therapeutic proposals about a society symptom].
AB  - The symptom of << king-child >> can, in some circumstances, damage the familial
      relationships. It leads the childhood professionals to think about the concepts
      this behaviour highlights, as well on the parents'as on the child's side: what is
      authority today? How can we combine familiar relationships and educational
      structure? Do we have to set limits to the child? This article suggests to
      consider the evolution of mentalities within the society and to develop, based on
      the foundations of the main psychoaffective marks of child development, the
      intentions of therapeutic support. Different lines of help and care get
      integrated into the familial therapy being as we think, the main element in the
      treatment of this symptom.

PMID- 15979863
TI  - [Finger trauma in children: errors to be avoided].
AB  - Two types of digital trauma are often met: in the young child, it is generally
      about a fingertip crushing by a door. In the event a of nail bed wound, the child
      will have to be addressed for a surgical treatment, the absence of a correct
      treatment being able to be responsible for after-effect. In the older child, the
      trauma is generally indirect during a sports activity or a game. Radiography
      often shows a fracture of phalanx epiphysal plate. The treatment is generally
      orthopaedic: simple immobilization if the fracture is not displaced, reduction
      and immobilization in the event of displaced fracture.

PMID- 15979864
TI  - A simplified laminin nomenclature.
AB  - A simplification of the laminin nomenclature is presented. Laminins are
      multidomain heterotrimers composed of alpha, beta and gamma chains. Previously,
      laminin trimers were numbered with Arabic numerals in the order discovered, that
      is laminins-1 to -5. We introduce a new identification system for a trimer using
      three Arabic numerals, based on the alpha, beta and gamma chain numbers. For
      example, the laminin with the chain composition alpha5beta1gamma1 is termed
      laminin-511, and not laminin-10. The current practice is also to mix two
      overlapping domain and module nomenclatures. Instead of the older Roman numeral
      nomenclature and mixed nomenclature, all modules are now called domains. Some
      domains are renamed or renumbered. Laminin epidermal growth factor-like (LE)
      domains are renumbered starting at the N-termini, to be consistent with general
      protein nomenclature. Domain IVb of alpha chains is named laminin 4a (L4a),
      domain IVa of alpha chains is named L4b, domain IV of gamma chains is named L4,
      and domain IV of beta chains is named laminin four (LF). The two coiled-coil
      domains I and II are now considered one laminin coiled-coil domain (LCC). The
      interruption in the coiled-coil of beta chains is named laminin beta-knob (Lbeta)
      domain. The chain origin of a domain is specified by the chain nomenclature, such
      as alpha1L4a. The abbreviation LM is suggested for laminin. Otherwise, the
      nomenclature remains unaltered.

PMID- 15979865
TI  - Lipoxins and aspirin-triggered lipoxins in neutrophil adhesion and signal
      transduction.
AB  - Lipoxin A4 (LXA4) and aspirin-triggered 15-epi-LXA4 (ATL) are emerging as
      endogenous braking signals for neutrophil-mediated tissue injury. LXA4 and ATL
      and their metabolically stable analogues display potent inhibitory actions in
      human isolated cells and blood, including attenuation of expression of adhesion
      molecules on leukocytes and endothelial cells, neutrophil adhesion to endothelial
      cells and platelets under shear, and IL-8 production, key events of the acute
      inflammatory response. The underlying molecular mechanisms include interference
      with MAPK signaling pathways, modulation of the oxidative chemistry of
      superoxide, NO and ONOO-, inhibition of activation of NF-kappaB and AP-1, and
      consequently the expression of interleukin-8 and likely other pro-inflammatory
      genes. Collectively, these results add to the profile of LXA4/ATL rapid actions
      that contribute to "stop signaling" involved in regulating neutrophil functions
      during acute inflammation and suggest that aspirin inhibits neutrophil
      accumulation through triggering the synthesis of 15-epi-LXA4.

PMID- 15979866
TI  - Cystic fibrosis and lipoxins.
AB  - Dysregulated neutrophilic inflammation and chronic infection lead to progressive
      destruction of the airways in cystic fibrosis (CF). Despite considerable recent
      progress in therapy, the median survival of patients with CF remains around 30
      years. The lipoxins are endogenous anti-inflammatory lipid mediators that are
      important regulators of neutrophilic inflammation. Recent data indicate that
      there is a pathophysiologically important defect in lipoxin-mediated anti
      inflammatory activity in the CF airway, suggesting novel approaches to
      pathogenesis and therapy in this lethal genetic disease.

PMID- 15979867
TI  - Lipoxin signaling in neutrophils and their role in periodontal disease.
AB  - Endogenous molecules involved in counterregulation of inflammatory responses
      provide an opportunity to explore new therapeutic approaches based on
      manipulation of new pathways that may reduce the possibility of unwanted toxic
      side effects. Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that
      are generated within the vascular lumen during cell-cell interactions or at
      mucosa through leukocyte-epithelial cell interactions. Transcellular biosynthetic
      pathways are the major lipoxin biosynthetic routes where LX are formed in vivo
      during inflammation and serve as "stop signals" that regulate key steps in
      leukocyte trafficking. In this review, recent findings in lipoxin generation,
      impact on the resolution of acute inflammation, and organ protection from
      neutrophil-mediated injury are presented. Periodontitis, specifically localized
      aggressive periodontitis, which is recognized as an example of neutrophil
      mediated tissue injury, is discussed as a disease model where LX and other
      endogenous pro-resolution pathway mediators could have potential value.

PMID- 15979868
TI  - Study of drying systems for the utilization of biodegradable municipal solid
      wastes as animal feed.
AB  - The effectiveness of different drying systems used for the dehydration of certain
      fractions of biodegradable municipal solid wastes with a high moisture content
      (fruit and vegetable remains) was analyzed. Some tests using small amounts of the
      material were carried out in natural and forced convection ovens. For larger
      quantities of wastes, a discontinuous cabinet dryer and a continuous rotary dryer
      were used. With these dryers, the moisture content was reduced from 800 to 100 g
      kg(-1). It was verified that the continuous rotary dryer was the most efficient
      type of equipment studied, since it allowed a dried waste to be obtained with
      better nutritional and microbiological qualities and in accordance to the
      specifications of the products for animal feeding.

PMID- 15979869
TI  - Removal of batteries from solid waste using trommel separation.
AB  - This paper describes the design and testing of a trommel for separation of
      batteries from solid waste. A trommel is a cylindrical separation device that
      rotates and performs size separation. It has also been used in areas such as
      municipal solid waste (MSW) processing, classifying construction and demolition
      debris, screening mass-burn incinerator ash and compost processing. A trommel has
      been designed based on size separation to separate household batteries from solid
      waste, which can then be used as feedstock for alternative applications of solid
      waste combustion, particularly where the metal content of the product is also a
      critical parameter, such as the Co-Co process for integrated cement and power
      production. This trommel has been tested with batches of university office and
      restaurant wastes against various factors. The recovery efficiency of batteries
      increases with decreasing inclination angle of the trommel and decreasing
      rotational speed. A physical characterization of the university solid waste has
      been performed with a 20-kg sample of the tested waste. It was found that there
      is a trend of decreasing recovery of batteries with increasing paper composition,
      and a trend of increasing recovery of batteries with increasing organic materials
      composition.

PMID- 15979870
TI  - Assisting Hox proteins in controlling body form: are there new lessons from flies
      (and mammals)?
AB  - Hox proteins regulate specific sets of target genes to give rise to morphological
      distinctions along the anterior-posterior body axis of metazoans. Though they
      have high developmental specificity, Hox proteins have low DNA binding
      specificity, so how they select the appropriate target genes has remained
      enigmatic. There is general agreement that cofactors provide additional
      specificity, but a comprehensive model of Hox control of gene expression has not
      emerged. There is now evidence that a global network of zinc finger transcription
      factors contributes to patterning of the Drosophila embryo. These zinc finger
      proteins appear to establish fields in which certain Hox proteins can function.
      Though the nature of these fields is uncertain at this time, it is possible that
      these zinc finger proteins are Hox cofactors, providing additional specificity
      during Hox target-gene selection. Furthermore, these zinc finger proteins are
      conserved, as are aspects of their anterior-posterior expression, suggesting that
      their roles might be conserved, as well. Perhaps this layer in the genetic
      control of body patterning will help bridge some of the chasms that remain in our
      understanding of the genetic control of pattern formation.

PMID- 15979871
TI  - Differential regulation of the human MRP2 and MRP3 gene expression by
      glucocorticoids.
AB  - Multidrug resistance proteins, which catalyse the detoxification of xenobiotics
      and excretion of metabolites, are very often controlled at the transcriptional
      level by interaction of exogenous compounds or hormones with nuclear receptors.
      Since synthetic glucocorticoids have found extensive use as anti-inflammatory
      drugs, also in the inhaled form in the treatment of asthma, lung cancer is
      potentially highly prone to transcriptional induction of multidrug resistance
      proteins by these steroids. MRP3 and MRP2 are major active anionic conjugate
      transporters in human cells and play a significant role in clinical multidrug
      resistance in cancer. A549 cells (non-small-cell lung cancer cell line) were
      challenged with glucocorticoids (dexamethasone, hydrocortisone and prednisone) at
      physiologically and therapeutically relevant concentrations for 24h and changes
      in MRP2 and MRP3 expression were followed on four levels: promoter regulation
      (luciferase reporter constructs), mRNA level (semi-quantitative real-time PCR),
      protein level (Western blotting) and activity (drug resistance and cellular
      transport of the model substrate calcein). DEX and HCT in the submicromolar
      concentration range caused a 2-fold induction of transcriptional activity at the
      MRP3 promoter construct, while MRP2 expression was not activated. All
      investigated glucocorticoids caused a modest stimulation of organic anion
      transport activity. We conclude that glucocorticoids used in clinical practice
      have the ability to transcriptionally upregulate human MRP3 gene expression in
      lung-derived cells where this protein is a major component of the organic anion
      extrusion system. This phenomenon has to be taken into account when designing
      treatments for lung cancer, especially for patients treated simultaneously with
      glucocorticoids against inflammatory symptoms.

PMID- 15979872
TI  - Bioconversion of waste office paper to gluconic acid in a turbine blade reactor
      by the filamentous fungus Aspergillus niger.
AB  - Gluconic acid production was investigated using an enzymatic hydrolysate of waste
      office automation paper in a culture of Aspergillus niger. In repeated batch
      cultures using flasks, saccharified solution medium (SM) did not show any
      inhibitory effects on gluconic acid production compared to glucose medium (GM).
      The average gluconic acid yields were 92% (SM) and 80% (GM). In repeated batch
      cultures using SM in a turbine blade reactor (TBR), the gluconic acid yields were
      60% (SM) and 67% (GM) with 80-100 g/l of gluconic acid. When pure oxygen was
      supplied the production rate increased to four times higher than when supplying
      air. Remarkable differences in the morphology of A. niger and dry cell weight
      between SM and GM were observed. The difference in morphology may have caused a
      reduction of oxygen transfer, resulting in a decrease in gluconic acid production
      rate in SM.

PMID- 15979873
TI  - Influences of vermicomposts on field strawberries: part 2. Effects on soil
      microbiological and chemical properties.
AB  - The effects of applications of food waste and paper waste vermicomposts on some
      soil chemical and biological properties were evaluated in field plots planted
      with strawberries. Six-week old strawberries (Fragaria ananasa, var. Chandler)
      were transplanted into 4.5 m(2) raised beds under a plastic tunnel structure
      measuring 9.14 x 14.6 x 3.6 m. Vermicompost were applied at rates of 5 or 10 t
      ha(-1) supplemented with inorganic fertilizers to balance fertilizer
      recommendations for strawberries of 85-155-125 kg NPK ha(-1). Effects of
      vermicomposts on strawberry growth and yields have been reported previously
      [Arancon, N.Q., Edwards C.A., Bierman P., Welch, C., Metzger, J.D., 2004. The
      influence of vermicompost applications to strawberries: Part 1. Effects on growth
      and yield. Bioresource Technology 93:145-153]. Total extractable N, NH(4)-N,
      NO(3)-N and orthophosphates did not differ significantly between treatments,
      except on the last sampling date (harvest date) in which significantly greater
      amounts of NH(4)-N, NO(3)-N and orthophosphates (P <or= 0.05) were recorded in
      vermicompost-treated soils than in the controls. Two major results of
      vermicompost applications to soils were increases in dehydrogenase activity and
      microbial biomass-N which were not dose-dependent. Increased dehydrogenase
      activity and microbial biomass-N was correlated positively with the increased
      amounts of NH(4)-N, NO(3)-N and orthophosphates in the vermicompost-treated plots
      than in the controls. Increases in microbial populations and activities are key
      factors influencing rates of nutrient cycling, production of plant growth
      regulating materials, and the build-up of plant resistance or tolerance to crop
      pathogen and nematode attacks.

PMID- 15979874
TI  - Discodermolide analogues as the chemical component of combination bacteriolytic
      therapy.
AB  - The marine natural product (+)-discodermolide (1) and several simplified
      analogues of this microtubule-stabilizing agent have proven to be potent in vitro
      cell growth inhibitory agents in several human cancer cell lines. Here, we
      demonstrate the in vivo efficacy of discodermolide and several simplified
      congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3
      anhydrodiscodermolide (3), as a chemical component of the combination
      bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically
      modified Clostridium novyi-NT spores caused rapid and complete regressions of
      tumors in mice bearing HCT116 colorectal cancer xenografts.

PMID- 15979875
TI  - Comparison of gait kinematics in patients receiving minimally invasive and
      traditional hip replacement surgery: a prospective blinded study.
AB  - Minimally invasive (MI) total hip replacement (THR) supposedly provides improved
      ambulation in the immediate post-operative period. This study used a prospective
      blinded design to analyse early post-operative walking ability using gait
      analysis. Seventeen patients were available for full analysis with nine having
      had the MI technique and eight having the standard incision (SI) technique.
      Patients were blinded as to the incision used, as were all physiotherapists and
      assessors. Differences in temporal-spatial variables and joint kinematics
      measured 1 day pre-operatively, 2 days post-operatively and 42 days (6 weeks)
      post-operatively were compared between groups. There was no significant
      difference in velocity, step length of the affected or unaffected leg, stride
      length or stance phase duration between the MI and SI groups between any of the
      timepoints tested. There was no significant improvement in the gait kinematics of
      the MI group compared to the SI group either 2 days post-operatively or 6 weeks
      post-operatively. Contrary to previous studies, there was no improvement in early
      post-operative gait for those patients who received THR using the minimally
      invasive technique.

PMID- 15979876
TI  - Eversion or subluxation of patella in soft tissue balancing of total knee
      arthroplasty? Results of a cadaver experiment.
AB  - Correct postoperative leg alignment and stability of total knee prosthesis over
      the full range of movement are critical factors for successful TKA. This is
      achieved by correct implantation of prosthesis and soft tissue handling. However,
      the surgical approach and how to displace the patella are still controversial. We
      have carried out a cadaver study looking at the effect of patella eversion or
      subluxation on limb axis alignment during balancing of the knee in three
      different standard surgical approaches; subvastus, midvastus, or medial
      parapatellar. For each approach, five knees were studied. Leg alignment was
      visualised by the Ci CT-free DePuy/BrainLAB navigation system. Using a navigation
      system alignment was determined in the AP axis in both extension and 90 flexion,
      with the patella everted as well as subluxated. Eversion of the patella gave a
      more valgus axis reading than subluxation in both extension 0.58 (SD: 0.03, range
      0.54 -0.60 ) and 90 flexion 0.48 (SD: 0.11, range 0.38 -0.60 ). The effect was
      greatest using the medial paraptellar approach. Surgeons should be aware that
      everting the patella influences the AP alignment when soft tissue balancing in
      total knee replacement.

PMID- 15979877
TI  - Accuracy of implantation of components in the Oxford knee using the minimally
      invasive approach.
AB  - Screened postoperative X-rays of 224 Oxford knees implanted through the minimally
      invasive approach were analysed using 16 criteria. The technique was as
      recommended by the Oxford Group except that the femoral intramedullary rod was
      used only as a guide to flexion/extension of the femoral component. All femoral
      components were within the recommended range for varus/valgus and mediolateral
      position. Eighteen femoral components were either too flexed or extended, but by
      a maximum of only 10 degrees . Tibial components were inserted in slight varus
      (mean 1.8 degrees , S.D. 8.8, range 10 to -10). All were within the range for
      posterior slope in spite of difficulty in establishing objective landmarks.
      Tibial coverage was imprecise with the phase 3 implants which were short and
      broad relative to the cut surface. In 36% of knees the tibial tray was implanted
      too anterior resulting in posterior under hang. There have been no clinical signs
      to indicate tipping of the meniscus in deep flexion. The depth of cement
      penetration under the keel was excessive in three cases, resulting from porotic
      bone rather than technical error in the depth of the cut. There has been one case
      of femoral component loosening following a fall and no tibial loosening in spite
      of imprecise alignment of some components.

PMID- 15979878
TI  - ESR studies on DNA cleavage induced by enediyne C-1027 chromophore.
AB  - C-1027 belongs to the family of chromoprotein antitumor antibiotics, which
      contain a carrier apoprotein and a highly unstable enediyne chromophore. The
      enediyne spontaneously aromatizes to generate p-benzyne biradical, and
      subsequently abstracts hydrogens from the DNA sugar backbone, resulting in
      cleavage of the double strand. Using spin-trapping methods, we obtained direct
      proof of radical intermediates during an DNA cleavage, and found intriguing
      difference in behavior between the trapping agents 2-methyl-2-nitrosopropane
      (MNP) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO): MNP added to the sugar
      radicals of the DNA, whereas DMPO directly trapped a phenyl radical or p-benzyne
      biradical derived from the C-1027 chromophore.

PMID- 15979879
TI  - The HYDAD-D antipersonnel landmine detector.
AB  - HYDAD (HYdrogen Density Anomaly Detection) systems have been developed to detect
      small (>200 g) antipersonnel landmines (APM) of plastic construction. The HYDAD-D
      detector is based on the earlier HYDAD designs HYDAD-H and HYDAD-VM. It consists
      of a neutron source and two identical slow neutron detectors. The difference
      between the responses of the two detectors is monitored as a function of position
      in the minefield and APM detection is based on an analysis of this difference.
      Laboratory tests and Monte Carlo simulations demonstrate that HYDAD-D is capable
      of detecting the IAEA standard dummy landmine DLM2 at burial depths up to 23 cm
      in dry sand and at burial depths up to 7 cm in damp sand containing 12% (by mass)
      water.

PMID- 15979880
TI  - Proteomic analysis of glial fibrillary acidic protein in Alzheimer's disease and
      aging brain.
AB  - Chronic inflammation is known to play an important role in the heterogeneous
      pathogenesis of Alzheimer's disease (AD). Activated astrocytes expressing glial
      fibrillary acidic protein (GFAP) are closely associated with AD pathology, such
      as tangles, neuritic plaques and amyloid depositions. Altogether, 46 soluble
      isoforms of GFAP were separated and most of them quantified by two-dimensional
      immunoblotting in frontal cortices of AD patients and age-matched controls. A 60%
      increase in the amount of more acidic isoforms of GFAP was observed in AD and
      these isoforms were both phosphorylated and N-glycosylated, while more basic
      isoforms were O-glycosylated and exhibited no quantitative differences between
      post-mortem AD and control brains. These data highlight the importance of
      exploring isoform-specific levels of proteins in pathophysiological conditions
      since modifications of proteins determine their activity state, localization,
      turnover and interaction with other molecules. Mechanisms, structures and
      functional consequences of modification of GFAP isoforms remain to be clarified.

PMID- 15979881
TI  - A defect in glyoxysomal fatty acid beta-oxidation reduces jasmonic acid
      accumulation in Arabidopsis.
AB  - The final steps of jasmonic acid (JA) biosynthesis are thought to involve
      peroxisomal beta-oxidation, but this has not been directly demonstrated. The last
      and key step in fatty acid beta-oxidation is catalyzed by 3-ketoacyl-CoA thiolase
      (KAT) (EC 2.3.1.16). A mutant of Arabidopsis thaliana ecotype Landsberg erecta,
      which lacks a functional KAT protein and is defective in glyoxysomal fatty acid
      beta-oxidation has been reported. In this study, the mutant was found to
      accumulate reduced level of JA in both its wounded cotyledons and leaves, while
      only the cotyledons accumulate 3-oxo-2-(pent-2'-enyl)-cyclopentane-1-octanoic
      acid (OPC-8:0). This indicates that a defect in one of the thiolase isoenzymes
      impairs beta-oxidation of OPC-8:0 to JA. The mutant had sufficient thiolase
      activity for the synthesis of JA in the unwounded but not in the wounded tissues.
      Activities of the enzymes in the JA pathway that catalyze the steps, which
      precede beta-oxidation were not altered by the mutation in a thiolase protein.
      Thus, reduced levels of JA in the wounded tissues of the mutant were attributed
      to the defect in a thiolase protein.

PMID- 15979882
TI  - Multivariate analysis of predictors of late stroke after total aortic arch
      repair.
AB  - OBJECTIVE: The number of aortic surgeries has recently increased, with
      improvement of outcome due to the development of various novel operative
      techniques and adjuncts. Although the postoperative incidence of stroke, the most
      severe complication of aortic surgery, is still a matter of concern and has been
      described well previously, late stroke after aortic arch repair has not been
      described well. We assessed the incidence and predictors of late stroke after
      total aortic arch repair. METHODS: From January 1993 to December 2003, 470
      patients underwent total aortic arch repair in our institution. All patients,
      whether undergoing elective, urgent, or emergent aortic arch repair, were
      included. Emergent operation was required for 115 patients because of rupture or
      acute type A dissection. For brain protection, retrograde cerebral perfusion was
      used in 27% (125) and selective cerebral perfusion in 75% (353) of cases. The
      follow-up period was 32.5+/-31.5 months. Late stroke was defined as stroke
      occurring more than 30 days postoperatively. RESULTS: The incidence of early
      postoperative stroke was 4.9% (23/470), while that of late postoperative stroke
      was 6.0% (28/470). On univariate analysis, postoperative atrial fibrillation
      (P=0.014), preoperative prevalence of craniocervical lesions (P=0.0001), and
      advanced age (P=0.046) were each significantly related to late stroke. A Cox
      proportional hazards model detected postoperative atrial fibrillation (P=0.013,
      OR=3.02, 95% CI: 1.26-7.24) and preoperative prevalence of craniocervical lesions
      (P=0.0001, OR=5.37, 95% CI: 2.30-12.52) as predictors of late stroke.
      CONCLUSIONS: Postoperative atrial fibrillation and preoperative prevalence of
      craniocervical lesions were found to be risk factors for late stroke after total
      aortic arch repair.

PMID- 15979883
TI  - OPCAB: time to call off the search for the Holy Grail!

PMID- 15979884
TI  - Does Hypericum perforatum L. extract show any specificity as photosensitizer for
      HL-60 leukemic cells and cord blood hemopoietic progenitors during photodynamic
      therapy?
AB  - Autologous bone marrow transplantation is a therapeutic modality that increases
      the survival rates for children with malignancies with poor prognosis but relapse
      rates are high and attributed partially to the existence of residual malignant
      cells. Photodynamic treatment (PDT) has been developed among purging strategies.
      We investigated the effect of the methanolic extract (ME) and its polar
      methanolic fraction (PMF) of Hypericum perforatum L., as a new photosensitizer
      for the leukemic cell line HL-60 and cord blood (CB) hemopoietic progenitors as
      well as the subcellular localization of the photosensitizer. METHODS: ME and PMF
      were prepared after extraction of the dry herb with methanol (ME), followed by
      liquid-liquid extraction with petroleum ether (PMF). Cells were incubated with
      the extracts before irradiation with Nd-Yvo Laser. Various concentrations of PMF
      or ME as well as irradiation doses were tested. Following irradiation, cell
      viability was determined by trypan blue in continuous liquid cultures for HL-60
      cells and in clonogenic assays for CB cells. The subcellular localization of the
      photosensitizer was determined by confocal microscopy. RESULTS: Laser
      photoirradiation in the presence of both PMF and ME induces the killing of HL-60
      cells. This effect is dose dependent. No CFU-GM and BFU-E growth was observed
      from CB mononuclear cells under the tested experimental conditions. Confocal
      microscopy revealed that the extracts localize mainly in the cytoplasm of the
      cells. CONCLUSIONS: PDT with both PMF and ME induces the killing of HL-60
      leukemic cells and the optimal conditions of treatment were determined. This
      effect of PDT/PMF was also exerted on CB progenitor cells indicative of the non
      selective uptake of the photosensitizer by malignant cells. Though this suggests
      that PDT/PMF cannot be helpful in autologous bone marrow purging, these novel
      extracts can however be beneficial in the PDT treatment of tumors given their
      photostability, low toxicity and low cost.

PMID- 15979885
TI  - Interaction of pyrene-end-capped poly(ethylene oxide) with bovine serum albumin
      and human serum albumin in aqueous buffer medium: a fluorometric study.
AB  - The photophysical behavior of a hydrophobically tailored water-soluble polymer,
      pyrene-end-capped poly(ethylene oxide) (PYPY), has been studied in aqueous
      buffered bovine serum albumin (BSA) and human serum albumin (HSA) media. In
      buffered aqueous solution the polymer shows dual emission corresponding to the
      monomer and the excimer of pyrene moiety. The relative intensity of the monomer
      to the excimer emission shows interesting variation with the addition of BSA and
      HSA and is indicative of significant interaction of these albumin proteins with
      the polymer. The binding interaction has been shown to have a prominent role on
      the steady state fluorescence anisotropy of the two emission bands. Attempt has
      been made to determine the micropolarities of the protein microenvironments from
      a comparison of the variation of the monomer to excimer relative fluorescence
      intensities of the probe in water-dioxane mixtures with varying composition.

PMID- 15979886
TI  - Age, cancer and the risk of venous thromboembolism.
AB  - Cancer increases the risk for venous thromboembolism (VTE) and patients
      presenting with a seemingly idiopathic VTE often have an occult cancer. Aging
      also is a risk factor for VTE. Therefore, old patients with cancer are supposed
      to be at very high risk for VTE, but inherent data are sporadic and contrasting.
      We reviewed the literature about the relation between cancer and VTE, with
      particular attention to findings concerning elderly patients. While aging and
      postmenopausal status enhance the risk of chemotherapy-induced VTE in women with
      breast cancer, the rate of a cancer diagnosis in the first year after VTE seems
      to be even lower in elderly compared to young subjects. Thus, further studies are
      needed to understand whether or not aging and cancer have additive thrombogenic
      effects. Finally, we discuss prophylactic and therapeutic strategies.

PMID- 15979887
TI  - Adjuvant chemo- and radiotherapy for poor prognosis head and neck squamous cell
      carcinomas.
AB  - The treatment of squamous cell carcinomas of the head and neck is
      multidisciplinary, especially when the disease is diagnosed at an intermediate or
      advanced stage. Very often the clinician chooses between surgery, chemo- and
      radiotherapy options on the basis of the most recent data from the literature,
      prior experience in head and neck oncology and patient preferences. Nevertheless,
      for operable tumors, primary surgery, combined in poor-risk patients with
      radiation, is traditionally considered as the approach offering the best
      opportunity of cure. Randomized controlled trials and meta-analyses conducted in
      the 1990s have demonstrated major improvements not only in loco-regional tumor
      control, but also in terms of survival when chemotherapy is added to radiotherapy
      in the post-operative setting. The therapeutic index yielded by the co
      administration of cytotoxic agents and ionizing radiation following primary
      surgery as compared with radiotherapy alone has nevertheless been at the center
      of many debates recently. Notwithstanding the fact that two randomized trials
      have recently provided new evidence that adjuvant chemo-radiation in poor-risk
      patients improves loco-regional control and disease-free survival, a number of
      questions regarding the optimization of the post-operative approaches remain
      unanswered. There is remaining need for further research efforts that would
      enable scientists and clinicians to improve, in the next decade, the management
      of this complex entity of diseases.

PMID- 15979888
TI  - Novel treatments for metastatic renal cell carcinoma.
AB  - The mainstay of any curative treatment in renal cell carcinoma (RCC) is surgery.
      In case of metastatic disease at presentation a radical nephrectomy is
      recommended to good performance status patients prior to start of interferon-alfa
      treatment. Interferon-alpha (IFN-alpha) offers in a small but significant
      percentage of patients advantage in overall survival; interleukin-2 (IL-2) based
      therapy gives similar survival rates. To date hormonal and chemotherapy do not
      have a proven impact on survival. The recent new insights in the molecular
      biology of clear RCC has revealed a key-role for vascular endothelial growth
      factor (VEGF) in the stimulation of angiogenesis in this highly vascularized
      tumour. This opens interesting new treatment strategies including: blockage of
      VEGF with the monoclonal antibody bevacizumab and inhibition of VEGF receptor
      tyrosine kinases (with small oral molecules such as SU11248 or PTK787). Likewise,
      inhibition of the Raf kinase pathway (with oral Bay 43-9006) or inhibition of the
      mTOR pathway (with i.v. CCI-779) are under investigation. Preliminary clinical
      results with all these compounds are interesting and the results of ongoing phase
      III studies will become available in the next years.

PMID- 15979889
TI  - Incidence and risk factors for cancer after liver transplantation.
AB  - De novo tumors (DNT) are a serious complication after orthotopic liver
      transplantation (OLT), showing a higher overall incidence ranging from 4.7% to
      15.7% in non-selected series. Skin cancer (SC) is the most frequent malignancy
      observed, ranging from 6% to 70% of the tumors observed, followed by post
      transplant lymphoproliferative disorders (PTLD) (4.3-30%). Different
      immunosuppressive protocols do not seem to influence DNT appearance. Colon and
      upper aerodigestive cancer after OLT seems to be more prone to develop when there
      are associated risk factors, such as primary sclerosing cholangitis (PSC) and
      alcoholic liver cirrhosis (ALC). Some risk factors, such as age, smoking, alcohol
      and others seem to play a role in higher risk for malignancy, but the presence of
      a long-term immunosuppressive state, more than the specific regimen used, is the
      basis for this higher incidence. Ethnic and demographic factors are also
      important variables influencing the heterogeneity of the results, especially
      influencing Kaposi's sarcoma and skin tumors.

PMID- 15979890
TI  - Prognostic impact of increasing age and co-morbidity in cancer patients: a
      population-based approach.
AB  - This large population-based study focuses on the prognostic role of increasing
      age and co-morbidity in cancer patients diagnosed in the southern Netherlands.
      Data of patients diagnosed between 1995 and 2002 and recorded in the population
      based Eindhoven Cancer Registry were used. Older patients (with serious co
      morbidity) with non-small cell lung cancer or prostate cancer underwent surgery
      less often than younger patients. Elderly with stage III colon cancer, small cell
      lung cancer, FIGO II or III ovarian cancer or non-Hodgkin's lymphoma (NHL)
      received (adjuvant) chemotherapy less often, probably because of the higher rate
      of haematological complications. Administration of adjuvant radiotherapy
      decreased with age and co-morbidity in patients with rectal cancer, limited small
      cell lung cancer or breast cancer. In general, elderly did not suffer from more
      complications than younger patients, except for cardiac complications (colorectal
      cancer and NHL) and postoperative death (non-small cell lung cancer). For most
      tumours relative survival was lower for the elderly, except for patients with
      colon cancer, prostate cancer or indolent NHL. Co-morbidity had an independent
      prognostic effect, except for tumours with a very poor prognosis. Future
      prospective studies should investigate whether the guidelines for cancer
      treatment should be adjusted for elderly with serious co-morbidity.

PMID- 15979891
TI  - Lymphocyte subsets and cytokines in women with gestational diabetes mellitus and
      their newborn.
AB  - This study aimed to identify potential immunological markers for predicting type
      1 diabetes in patients with gestational diabetes mellitus (GDM) and any
      immunological impairment in their newborn. In 62 GDM patients and 74 women with
      normal glucose tolerance (NGT), and their babies, we assessed total lymphocytes,
      T lymphocyte subsets CD3 and CD8 expressing T cell receptor (TCR) alpha/beta or
      gamma/delta, CD16 and CD19, pancreatic autoantibodies and cytokines (IL-5, IL-2,
      soluble receptor IL-2). At delivery, umbilical cord blood samples were taken for
      lymphocyte subpopulations and cytokine measurements. GDM mothers had higher
      levels of total lymphocytes, CD8 expressing TCR gamma/delta, and lower levels of
      CD3 expressing TCR alpha/beta than NGT controls. Insulin-treated GDM mothers had
      lower CD4 and CD4/CD8 ratios, and higher CD8 and IL-5 than diet-treated GDM or
      controls. Five women were positive for pancreatic autoantibodies, with lower CD4
      (p<0.01) and CD4/CD8 ratios (p<0.05), and higher CD8 (p<0.03) and CD19 than GDM
      and control mothers negative for autoantibodies. GDM newborn had higher CD8
      gamma/delta and lower CD16 than NGT babies. There were no significant differences
      in TNF-alpha concentrations in the cord blood obtained from the GDM and NGT
      newborn. In conclusion, GDM women and their newborn have lymphocyte subset
      impairments, which are more important in patients positive for autoantibodies
      and/or treated with insulin.

PMID- 15979892
TI  - HPLC analysis of raloxifene hydrochloride and its application to drug quality
      control studies.
AB  - Raloxifene hydrochloride is a selective estrogen receptor modulator and is
      currently being used for prevention of osteoporosis in postmenopausal women. In
      this article, a high performance liquid chromatography (HPLC) method for
      detection of raloxifene hydrochloride was developed and validated using an
      ultraviolet (UV) and coulometric detectors. Limit of quantification (LOQ) was
      0.336 and 0.610 mg L(-1) for coulometric and ultraviolet detectors, respectively.
      Acceptable accuracy (93.1-100.3%) as well as intra- and inter-day precision
      (CV<or=2.38% and CV<or=7.93%, respectively) was demonstrated in the range of 0.5
      10 mg L(-1) for both detectors. The presented method was applied without any
      interference of excipients to the determination of raloxifene hydrochloride
      content in tablets and to the in vitro dissolution studies. The proposed method
      could be used for routine quality control. Moreover, due to its low LOQ,
      excellent accuracy, precision and selectivity, the coulometric detection could be
      applied to in vitro metabolism experiments such as microsome or hepatocyte
      preparations and for studies of transport of raloxifene hydrochloride across
      biological membranes.

PMID- 15979893
TI  - Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model
      for type 2 diabetes and pharmacological screening.
AB  - The objective of the present study was to develop a rat model that replicates the
      natural history and metabolic characteristics of human type 2 diabetes and is
      also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g)
      were divided into two groups and fed with commercially available normal pellet
      diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58%
      calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats
      exhibited significant increase in body weight, basal plasma glucose (PGL),
      insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared
      to NPD-fed control rats. Besides, the HFD rats showed significant reduction in
      glucose disappearance rate (K-value) on intravenous insulin glucose tolerance
      test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate
      (K-value) suggested that the feeding of HFD-induced insulin resistance in rats.
      After 2 weeks of dietary manipulation, a subset of the rats from both groups was
      injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)).
      Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection
      that, however, caused only mild elevation in PGL in NPD-fed rats. Though there
      was significant reduction in PI level after STZ injection in HFD rats, the
      reduction observed was only to a level that was comparable with NPD-fed control
      rats. In addition, the levels of PTG and PTC were further accentuated after STZ
      treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to
      significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat
      fed/STZ-treated rats simulate natural disease progression and metabolic
      characteristics typical of individuals at increased risk of developing type 2
      diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ
      treated rats were found to be sensitive for glucose lowering effects of insulin
      sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides,
      the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and
      PTC) was shown in these diabetic rats. The present study represents that the
      combination of HFD-fed and low-dose STZ-treated rat serves as an alternative
      animal model for type 2 diabetes simulating the human syndrome that is also
      suitable for testing anti-diabetic agents for the treatment of type 2 diabetes.

PMID- 15979894
TI  - Arsenic trioxide overcomes apoptosis inhibition in K562/ADM cells by regulating
      vital components in apoptotic pathway.
AB  - Extensive researches have revealed that arsenical can exert anti-tumor efficacy
      against several kinds of cancers including leukemia. Though, little is known
      about the effects of arsenical on leukemia resistant to chemotherapy, emerging as
      a serious clinical problem. In this study, we tested arsenic trioxide (As(2)O(3))
      induced apoptosis in K562/ADM multidrug-resistant leukemic cells and investigated
      its possible mechanisms. Using microscopy, flow cytometry (FCM) and DNA
      electrophoresis, we found that As(2)O(3) could induce the cells to undergo G2/M
      phase arrest and apoptosis. Further, it was shown that the levels of FAS and P53
      proteins increased and P-glycoprotein (P-gp) decreased upon drug action by
      employing FCM. Reverse transcription polymerase chain reaction (RT-PCR) detected
      increased mRNA product of FAS and caspase-3 genes and reduced MDR1 mRNA. CASPASE
      3 activity was also enhanced after As(2)O(3) treatment. However, the expression
      of BCL-2 protein was not affected by the drug. Taken together, As(2)O(3) is able
      to reverse the apoptosis resistance in drug-resistant K562/ADM cells by
      modulating expression or activity of key factors associated with apoptosis
      induction.

PMID- 15979895
TI  - Linking age-related defects in B lymphopoiesis to the aging of hematopoietic stem
      cells.
AB  - B cell genesis declines with age, but at what stage and why remains unclear.
      Previous studies attribute the decline in B cell production in aged mice to both
      environmental and cell-intrinsic defects that impact mid-to-late stream B cell
      precursors. However, mounting evidence suggests that the aging process may also
      negatively affect the earliest phases of B cell development. We review past
      studies on the B cells and aging question, discuss recent data suggesting that
      age-associated defects in B cell development reflect deficiencies in
      hematopoietic stem cell-proximal progenitor pools, and provide an integrative
      model that will hopefully facilitate further studies into this complex problem.

PMID- 15979896
TI  - Use of Ssp dnaB derived mini-intein as a fusion partner for production of
      recombinant human brain natriuretic peptide in Escherichia coli.
AB  - To prevent in vivo degradation, small peptides are usually expressed in fusion
      proteins from which target peptides can be released by proteolytic or chemical
      reagents. In this report, a modified Ssp dnaB mini-intein linked with a chitin
      binding domain tag was used as a fusion partner for production of human brain
      natriuretic peptide (hBNP), a hormone for the treatment of congestive heart
      failure. The fusion protein was expressed as an inclusion body in Escherichia
      coli. After refolding, the fusion protein was purified with a chitin affinity
      column, and dnaB mini-intein mediated peptide-bond hydrolysis was triggered by
      shifting the pH in the chitin column to 7.0 at 25 degrees C for 16 h, which led
      to the release and separation of hBNP from its fusion partner. The hBNP sample
      was further purified with reverse phase HPLC and its biological activity was
      assayed in vitro. It was found that hBNP had a potent vasodilatory effect on
      rabbit aortic strips with an EC(50) of (1.24+/-0.32)x10(-6)mg/ml, which was
      similar to that of the synthetic BNP standard. The expression strategy described
      here promises to produce small peptides without use of proteolytic or chemical
      reagents.

PMID- 15979897
TI  - A public software for energy filtering transmission electron tomography (EFTET
      J): application to the study of granular inclusions in bacteria from Riftia
      pachyptila.
AB  - Energy-filtering transmission electron microscopy (EFTEM) allows the
      determination of elemental distributions out of a sequence of energy filtered
      images. Combined with electron tomography, EFTEM is a powerful tool to obtain
      three-dimensional chemical maps from sub-cellular structures. However, there is
      no existing software in the public-domain for the computation and analysis of 3D
      chemical maps. Here, we present a Java-based program to compute 3D-elemental
      distribution. This program is available as a set of plug-ins for the public
      domain Java image processing program Image J inspired by NIH Image. Its
      implemented algorithms have been successfully applied to the three-dimensional
      localization of iron granules in semi thin (200 nm) epon sections from the vent
      worm Riftia pachyptalia.

PMID- 15979898
TI  - Phenoloxidase activity in three commercial bivalve species. Changes due to
      natural infestation with Perkinsus atlanticus.
AB  - The phenoloxidase (PO) activity of the haemolymph and haemocytes from three clam
      species of commercial interest (Ruditapes philippinarum, Chamelea gallina and
      Tapes decussatus) has been compared. The activity was assayed
      spectrophotometrically by recording the formation of dopachrome from L-DOPA using
      sodium dodecyl sulphate, laminarin, trypsin or lipopolysaccharide as elicitors.
      Fewer PO units were observed in the haemolymph from T. decussatus than in the
      haemolymph from R. philippinarum, while the highest values were found in C.
      gallina. In all cases the activity was only significantly increased when sodium
      dodecyl sulphate was used as elicitor. PO activity in the haemocytes of all three
      clam species showed a very similar pattern to that found in the haemolymph from
      the same species. Furthermore, T. decussatus naturally parasitized by Perkinsus
      atlanticus (Protozoa, Apicomplexa) was used to study the influence of such
      infestation on PO activity, which was found to increase significantly in both
      haemolymph and haemocytes compared with non-infected (control) samples. PO
      activity in the haemocytes and in the haemolymph was higher when the level of
      parasitization was low or medium, respectively, and SDS was used as elicitor. No
      statistically significant differences were observed when the parasitization level
      was high. The present work constitutes the first report on the influence of this
      parasite on PO activity in haemolymph and haemocytes from T. decussatus.

PMID- 15979899
TI  - Task constraints modulate activation in right ventral lateral prefrontal cortex.
AB  - Lesion data suggest that right prefrontal cortex (PFC) plays a critical role in
      open-ended problem solving. To test this hypothesis, we scanned fifteen normal
      subjects with fMRI as they completed three types of anagram problems varying in
      the level of constraints placed on the search space. On unconstrained trials,
      they rearranged letters to generate solutions (e.g., Can you make a "Word with
      ZJAZ?"). On semantically constrained trials, they rearranged letters to generate
      solutions within particular semantic categories (e.g., Can you make a type of
      "Music with ZJAZ?"). On baseline trials, they rearranged letters to make specific
      words (e.g., Can you make the word "JAZZ with ZJAZ?"). As predicted, the critical
      comparison of unconstrained vs. semantically constrained trials revealed
      significant activation in right ventral lateral PFC, as well as left superior
      frontal gyrus, frontopolar cortex, right superior parietal lobe, right post
      central gyrus, and the occipital-parietal sulcus. Furthermore, activation in
      right ventral lateral PFC (BA 47) increased as the constraints placed on the
      anagram search space were reduced. We argue that the activation in right ventral
      lateral PFC is related to hypothesis generation in unconstrained settings,
      whereas activation in other structures is related to additional processes linked
      to anagram problems such as semantic retrieval, semantic categorization, and
      cognitive monitoring. These results extend the lesion data and imaging studies by
      demonstrating that a relative absence of constraints on the solution space is
      sufficient to engage right ventral lateral PFC in hypothesis generation tasks.

PMID- 15979900
TI  - The C50m response: conditioned magnetocerebral activity recorded from the human
      brain.
AB  - Recent advances in neuroimaging technology now permit a precise determination of
      the dynamics of specific neural activity underlying human associative learning.
      We used magnetoencephalography (MEG) to characterize the dynamics of conditioned
      responses (CRs) within auditory cortex during habituation, delay and trace
      conditioning training, and delay conditioning extinction. Conditioned stimuli
      (CS) were visually presented geometric figures, and unconditioned stimuli (US)
      were aversive noise bursts. CS+ stimuli were paired with the US on 50% of
      presentations: CS- stimuli were never paired with the US. Auditory cortex was
      activated following the paired CS+ at an average of 49-62 ms following US onset.
      Our data support the presence of a differential conditioned response (C50m) in
      auditory cortex following the unpaired CS+ at an average of 30-61 ms after US
      omission. The current source strength of the auditory C50m was subsequently
      quantified for the unpaired CS+ and CS- during training, the unpaired CS+ during
      extinction, and habituation. During delay and trace training, the C50m was
      stronger for the unpaired CS+ than for the CS-, and was also stronger for the
      unpaired CS+ during training compared to both habituation and extinction. This is
      the first description of magnetocerebral conditioning in normal human auditory
      cortex. The C50m activity in auditory cortex elicited by visual stimuli
      constitutes a direct observation of associative neural plasticity within the
      human auditory cortex.

PMID- 15979901
TI  - How to achieve chronic intravenous drug self-administration in mice.
AB  - INTRODUCTION: Self-administration, the best animal model of drug addiction,
      requires implantation of indwelling jugular catheters. Surgical procedures in
      mice, the most common species for transgenic modeling, are difficult owing to
      size and scale. The goal of this paper was to describe how to achieve successful
      intravenous drug self-administration in mice. METHOD: The surgical and self
      administration training procedures developed for rats and other species have been
      adopted for mice and described in a step-by-step manner with reference to sources
      for equipment, materials, and parts. RESULTS: The method can be used for studying
      self-administration behavior in freely moving mice up to 4 weeks. The relatively
      quick loss of catheter patency was due to growth of neointima tissue. DISCUSSION:
      Drug self-administration is achievable in mice, and the model is limited only by
      eventual loss of catheter patency, a process probably triggered by mechanical
      damage of the endothelium, by the effect of drug injections, or a combination of
      these factors.

PMID- 15979902
TI  - Identification and expression of the amphioxus Cks1 gene.
AB  - A full-length Cks1 homologue gene, AmphiCks1, was identified in amphioxus,
      Branchiostoma belcheri tsingtauense. Sequence characteristics, phylogeny and
      patterns of expression during embryonic and larval development were established.
      The protein predicted from AmphiCks1 showed high sequence identity with
      vertebrate and invertebrate homologues. Protein structural studies and
      phylogenetic analysis suggested that Cks homologues are evolutionarily conserved.
      The AmphiCks1 transcript was detected in most early developmental stages by
      northern blotting and whole-mount in situ hybridization, suggesting a role for
      the gene in cell division.

PMID- 15979904
TI  - Osteocalcin is angiogenic in vivo.
AB  - The exact function of osteocalcin (OC), a protein synthesized by osteoblasts
      during the matrix mineralization phase, is still unknown. In this study we
      investigated the capacity of OC to promote vasoproliferation in chick embryo
      chorioallantoic membrane (CAM), a well established in vivo assay for angiogenesis
      and anti-angiogenesis. The results showed that OC stimulates angiogenesis and
      that the response is similar to that obtained with FGF-2, a well-known angiogenic
      cytokine. It has previously been demonstrated that OC is involved in bone repair,
      so the angiogenic activity reported here might also play a crucial role in bone
      formation.

PMID- 15979905
TI  - Oligomycin strengthens the effect of cyclosporin A on mitochondrial permeability
      transition by inducing phosphate uptake.
AB  - The purpose of this work was to assess the effect of oligomycin on the
      mitochondrial membrane permeability transition. The antibiotic was found to
      strengthen cyclosporin A (CSA)-induced protection of non-specific permeability,
      which is triggered by a matrix Ca2+ load in the absence of ADP. Oligomycin also
      reinforced the protective effect of CSA on carboxyatractyloside-induced pore
      opening in the absence of ADP, but failed to do so in mitochondria incubated
      under anaerobic conditions or after addition of CCCP. Analyzing the efflux of
      matrix Ca2+, we found that mitochondrial swelling and the collapse of the
      transmembrane electric gradient coincided with membrane leakage. The effects of
      the antibiotic were observed in phosphate-containing media but not in the
      presence of acetate. Furthermore, N-ethylmaleimide hindered the protective effect
      of oligomycin-CSA. In addition, the matrix phosphate concentration increased
      concurrently with a diminution in the matrix-free fraction of Ca2+. We concluded
      that oligomycin increases phosphate uptake by stimulating the phosphate-/OH-
      exchange reaction.

PMID- 15979906
TI  - Adhesiveness of beta5 integrin variant lacking FNK767-769 is similar to that of
      the prototype containing FNKFNK764-769.
AB  - Little is known about the functions of two different beta5 integrins: repeated
      FNK (FNKFNK764-769) and single-FNK (FNK764-766) amino acid sequences in the
      cytoplasmic domain. We examined whether they occurred as germ line mutations or
      somatic mutations associated with neoplastic transformation, and whether there
      were functional alterations. Out of six cultured cell lines, only KATO-III cells
      had the single-FNK beta5 sequence. The single-FNK beta5 was found in 9 out of 79
      patients with colon carcinoma, but no somatic mutations were detected in
      cancerous tissues. CHO cells were transformed with expression vectors containing
      single-FNK or repeated-FNK beta5 cDNA, which were derived from KATO-III cells.
      CHO cells transfected with single-FNK and repeated-FNK showed similar
      adhesiveness to, and proliferative activity on, vitronectin substrates.

PMID- 15979907
TI  - The sperm mitochondria-specific translocator has a key role in maternal
      mitochondrial inheritance.
AB  - The mechanism of maternal mitochondrial inheritance in animals involves the
      selective elimination of sperm mitochondria by the elimination factor of the egg
      and the sperm mitochondria-specific factor. In vitro fertilization using sperm
      from isogenic mice incorporating heterospecific mitochondrial DNA (mtDNA) showed
      that the number of PCR positives of sperm mtDNA in two-cell embryos was
      significantly increased following sperm incubation with anti-tetratricopeptide
      repeat-containing protein involved in spermatogenesis (tpis) protein, anti
      translocator of mitochondrial outer membrane (Tom) 22 and anti-Tom40 antibodies.
      The treatment of fertilized eggs with EGTA and other endonuclease inhibitors
      increased the sperm mtDNA levels. We conclude that the elimination factor, which
      is probably an endonuclease, is selectively received by the tpis protein of the
      sperm mitochondrial outer membrane within the egg. It is then transported into
      the sperm mitochondria by Tom22 and Tom40, where it destroys the sperm mtDNA,
      establishing the maternal inheritance of mtDNA.

PMID- 15979908
TI  - Characterization of ATP and ADP hydrolysis activity in rat gastric mucosa.
AB  - The degradation of nucleotides is catalyzed by the family of enzymes called
      nucleoside triphosphate diphosphohydrolases (NTPDases). The aim of this work was
      to demonstrate the presence of NTPDase in the rat gastric mucosa. The enzyme was
      found to hydrolyze ATP and ADP at an optimum pH of 8.0 in the presence of Mg2+
      and Ca2+. The inhibitors ouabain (0.01-1 mM), N-ethylmaleimide (0.01-4 mM),
      levamisole (0.10-0.2 mM) and Ap5A (0.03 mM) had no effect on NTPDase 1 activity.
      Sodium azide (0.03-30 mM), at high concentrations (>0.1 mM), caused a parallel
      hydrolysis inhibition of ATP and ADP. Suramin (50-300 microM) inhibited ATP and
      ADP hydrolysis at all concentrations tested. Orthovanadate slightly inhibited
      (15%) Mg2+ and Ca2+ ATP/ADPase at 100 microM. Lanthanum decreased Mg2+ and Ca2+
      ATP/ADPase activities. The presence of NTPDase as ecto-enzyme in the gastric
      mucosa may have an important role in the extracellular metabolism of nucleotides,
      suggesting that this enzyme plays a role in the control of acid and pepsin
      secretion, mucus production, and contractility of the stomach.

PMID- 15979909
TI  - Purmorphamine enhances osteogenic activity of human osteoblasts derived from bone
      marrow mesenchymal cells.
AB  - Purmorphamine is a novel small molecule with osteogenesis-inducing activity in
      multipotent mesenchymal progenitor cells, but there has been no evaluation of its
      effect on human cells to date. The aim of this study was to investigate the
      induction of osteogenic activity by purmorphamine in human osteoblasts
      differentiated from bone marrow mesenchymal cells. Cells were cultured in 24-well
      plates at a density of 2x10(4)/well in medium containing 1, 2 or 3 microM
      purmorphamine, or vehicle. At 7, 14 and 21 days, cell proliferation, viability,
      and alkaline phosphatase (ALP) activity were evaluated. Bone-like nodule
      formation was evaluated at 21 days. Purmorphamine did not affect cell
      proliferation or viability, but increased ALP activity and bone-like nodule
      formation. These results indicate that events related to osteoblast
      differentiation, including increased ALP activity and bone-like nodule formation,
      are enhanced by purmorphamine.

PMID- 15979910
TI  - Intracellular signal transduction pathways induced by leptin in C2C12 cells.
AB  - As experimental evidence suggests that leptin may have direct effects on
      peripheral tissues, we investigated some of the transductional molecules induced
      by leptin in C2C12 cells. In immunoprecipitation experiments using anti-p85
      antibodies (a regulatory subunit of phosphatidylinositol-3-kinase; PI3K), we
      observed a significant increase in PI3K activity. Immunoblot analyses showed that
      Akt, GSK3, ERK1, ERK2, and p38 mitogen-activated protein kinase (p38 MAPK)
      phosphorylation significantly increased after leptin treatment. Protein kinase C
      (PKC)-zeta was also activated by leptin, as documented by an immunocomplex kinase
      assay and immunoblotting experiments. The treatment of C2C12 cells with
      Wortmannin before leptin administration inhibited induction of the
      phosphorylation of ERKs (extracellular signal-regulated kinases) but not that of
      p38 MAPK, whereas pre-treatment with a PKC-zeta inhibitor partially decreased ERK
      phosphorylation. Taken together, our in vitro results further support the
      hypothesis that leptin acts acutely on skeletal muscle tissue through some of the
      components of insulin signalling, including PKC-zeta.

PMID- 15979912
TI  - Computed tomography guided lumbar sympathetic block for complex regional pain
      syndrome in a child: a case report and review.
AB  - The aim of this paper is to describe the first reported use of computed
      tomography (CT) guided lumbar sympathetic block as treatment of a case of complex
      regional pain syndrome (CRPS) in a child. The potential aetiology of CRPS is
      discussed in relation to the mechanism of action of local anaesthetics used in
      the block. Based on the successful treatment of this child and the documented
      success of its use in adults, we conclude that despite the minimal dose of
      radiation given, CT guided lumbar sympathetic block is an important treatment
      option in CRPS in children.

PMID- 15979913
TI  - Expression patterns of three heat shock protein 70 genes among developmental
      stages of the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae).
AB  - Three genes were identified encoding heat shock protein 70's in Tribolium
      castaneum (Herbst) and they were tentatively named as tchsp70 I, tchsc70 II, and
      tchsp70 III. Comparison of deduced amino acid sequences of tchsp70 I and tchsc70
      II showed 99% identity. However, the amino acid sequence of tchsp70 III was only
      58.5% identical to those of tchsp70 I and tchsc70 II. Stage-specific expression
      patterns of the tchsp70 were investigated in young larvae, old larvae, pupae, and
      adults of T. castaneum exposed for 1 h to 23 degrees C (control) or 40 degrees C
      (heat-shock). Northern blot and real-time quantitative PCR analyses were carried
      out to determine mRNA levels in each life stage. Transcripts of all three genes
      were detected by Northern blotting, and the sizes were 2.4- 2.2-, and 2.3-kb for
      tchsp70 I, tchsc70 II, and tchsp70 III, respectively. A 1.1- to 2.0-fold
      increased expression of tchsp70 I mRNA was found in heat-shocked developmental
      stages compared with the control. The expression of tchsc70 II mRNA among
      developmental stages was similar between heat-shocked and control insects, and
      the expression of tchsp70 III mRNA varied among developmental stages. Results
      suggest that the expression of tchsp70 I gene is heat-inducible, tchsc70 II is
      constitutive, and tchsp70 III is developmentally regulated in T. castaneum.

PMID- 15979914
TI  - Serotonergic immunoreactivity in the pedal ganglia of the pulmonate snail
      Megalobulimus abbreviatus after thermal stimulus: A semi-quantitative analysis.
AB  - Using an immunohistochemical procedure and optical densitometry, the distribution
      of neurons containing serotonin (5-HT) was investigated in the pedal ganglia of
      Megalobulimus abbreviatus after thermal "non-functional stimulus" (22 degrees C)
      and stressful thermal conditions (50 degrees C). The animals were sacrificed at
      different times (3 h, 6 h and 24 h) following these stimuli. In control animals,
      the results showed the location of these serotonergic immunoreactive elements
      (5HT-ir) in this ganglion to be similar to those shown in other studies, where
      the anterior region of ventral sections showed the largest number of 5HT-ir
      neurons. In the anterior neurons, significant differences (p < 0.01) were
      observed between the groups of animals stimulated at 50 degrees C and 22 degrees
      C and sacrificed after 6 h. In the medial neurons, significant differences (p <
      0.05) were observed between the control group and the groups of animals
      stimulated at 50 degrees C and sacrificed after 6 and 24 h. Neuropilar area 1
      showed differences (p < 0.01) in 5HT-ir between the control group and the groups
      of animals stimulated at 50 degrees C and sacrificed after 3 and 24 h. Neuropilar
      area 2 showed a significant difference (p < 0.05) between the groups of animals
      stimulated at 22 degrees C and sacrificed after 3 and 24 h. These results suggest
      the involvement of 5-HT in the nociceptive circuit of M. abbreviatus, mainly that
      of the medial neurons and neuropilar area 1, which showed increases in 5HT-ir
      after thermal aversive stimuli. These results could be helpful in drawing
      cellular homologies with other gastropods.

PMID- 15979915
TI  - The total length of myocytes and capillaries, and total number of myocyte nuclei
      in the rat heart are time-dependently increased by growth hormone.
AB  - Growth hormone (GH) can increase size and dimensions of rat hearts. The aim was
      to study how GH administration influences the growth of cardiac myocytes and
      capillaries in relation to time. Three-month-old female rats were divided into 10
      groups (n=3), and injected with either GH (5mg/kg/day) or vehicle for 5, 10, 20,
      40, or 80 days. From the left ventricle (LV) histological sections were made and
      stereological methods applied. Linear regression showed that GH time-dependently
      increased: LV volume (r=0.96, P<0.001), total volume of myocytes (r=0.96,
      P<0.001) and capillaries (r=0.64, P<0.05), total length of myocytes (r=0.90,
      P<0.001) and capillaries (r=0.78, P<0.001), and total number of myocyte nuclei
      (r=0.85, P<0.001). In conclusion, during 80 days of GH treatment the total volume
      and length of myocytes and capillaries, and total number of myocyte nuclei
      increased in a linear way. The results indicate that GH is a potent mediator of
      myocardial growth.

PMID- 15979917
TI  - Lysine and glutamate production by Corynebacterium glutamicum on glucose,
      fructose and sucrose: roles of malic enzyme and fructose-1,6-bisphosphatase.
AB  - In the biotechnological production of L-lysine and L-glutamate by Corynebacterium
      glutamicum media based on glucose, fructose or sucrose are typically used.
      Glutamate production by C. glutamicum was very similar on glucose, fructose,
      glucose plus fructose and sucrose. In contrast, lysine production of genetically
      defined C. glutamicum strains was significantly higher on glucose than on the
      other carbon sources. To test whether malic enzyme or fructose-1,6-bisphosphatase
      might limit growth and lysine on fructose, glucose plus fructose or sucrose,
      strains overexpressing either malE which encodes the NADPH-dependent malic enzyme
      or the fructose-1,6-bisphosphatase gene fbp were generated. Overexpression of
      malE did not improve lysine production on any of the tested carbon sources. Upon
      overexpression of fbp lysine yields on glucose and/or fructose were unchanged,
      but the lysine yield on sucrose increased twofold. Thus, fructose-1,6
      bisphosphatase was identified as a limiting factor for lysine production by C.
      glutamicum with sucrose as the carbon source.

PMID- 15979916
TI  - Effects of recombinant mouse growth hormone treatment on growth and body
      composition in GHRH knock out mice.
AB  - OBJECTIVE: GH deficiency (GHD) causes growth failure and alterations in body
      composition both in humans and mice. Mouse models of GHD are used to study the
      effect of GH replacement therapy on these parameters. As the administration of
      human GH to mice causes development of antibodies and progressive reduction of
      its effectiveness, the use of species-specific GH is recommended. To determine
      the optimal GH replacement schedule in GHD mice, and to study its effect on body
      composition, we treated mice with targeted ablation of the GHRH gene (GHRH knock
      out-GHRHKO) with recombinant mouse GH (rmGH). DESIGN: One week-old GHRHKO male
      animals received either placebo or one of two different regimens of escalating
      doses of rmGH: R1: 30 microg/daily (1st week), 50 microg/daily (2nd week), 70
      microg/daily (3rd-4th week); R2: 15 microg/twice a day (1st week), 25
      microg/twice a day (2nd week), 35 microg/twice a day (3rd-4th week). Sex- and age
      matched wild-type (WT) animals served as controls. At the end of the study we
      measured body length and weight, tibia and femur length, and body composition.
      RESULTS: While R1 normalized all growth parameters (TBW, N-A, femur, tibia
      length), R2 mice achieved significantly higher TBW, N-A and femur length when
      compared to WT. Body composition abnormalities (increased subcutaneous fat and
      reduced lean mass) were completely reverted by both treatment schedules. None of
      the GH-induced parameter modification described above was reflected in parallel
      changes in circulating serum IGF-1 and liver IGF-1 mRNA. CONCLUSIONS: Our
      findings indicate that in GHD mice body composition changes are reverted by rmGH
      and that twice/daily is more effective than daily administration.

PMID- 15979918
TI  - Cardiac manifestations in the mouse model of mucopolysaccharidosis I.
AB  - Mucopolysaccharidosis I (MPS I, alpha-l-iduronidase deficiency disease) is a
      heritable lysosomal storage disorder involving multiple organs, including the
      heart. Malfunction of the heart is also a major manifestation in the mouse model
      of MPS I, progressing in severity from 6 to 10 months (of a 1 year life span). In
      comparisons of MPS I with wild-type mice, the heart was found enlarged, with
      thickened septal and posterior walls, primarily because of infiltration of the
      muscle by storage-laden cells. Heart valves were enlarged and misshapen, and
      contained large numbers of highly vacuolated interstitial cells. The thickened
      aortic wall contained vacuolated smooth muscle cells and interrupted elastic
      fibers. Hemodynamic measurements and echocardiography revealed reduced left
      ventricular function as well as mitral and aortic regurgitation. But despite
      these abnormalities, free-roaming MPS I mice implanted with radio telemetry
      devices showed surprisingly normal heart rate and blood pressure, though their
      electrocardiograms were abnormal. An incidental finding of the telemetry studies
      was a disturbed circadian rhythm in the MPS I mice. Restoration of enzyme
      activity in the heart of one mouse, by transplantation of retrovirally modified
      bone marrow, resulted in normalization of left ventricular function as well as
      loss of storage vacuoles in myocytes and endothelial cells, though not in
      valvular interstitial cells. This study demonstrates the usefulness of the mouse
      model for in-depth studies of the cardiovascular component of MPS I.

PMID- 15979919
TI  - Mutation analysis of the PLOD1 gene: an efficient multistep approach to the
      molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS
      VIA).
AB  - The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) is an inheritable
      connective tissue disorder characterized by a deficiency of lysyl hydroxylase due
      to mutations in PLOD1. We describe a mutation analysis strategy for the PLOD1
      gene using either cDNA or gDNA or a combination thereof, which allows for
      reliable, time-effective and efficient mutation detection in patients with EDS
      VIA. We report the results obtained in 9 index patients from 12 unrelated
      families: three patients were homozygous for three novel mutations
      (p.Ile454IlefsX2, p.Ala667Thr, and p.His706Arg), four patients were homozygous
      for the common duplication of exons 10-16, one patient was compound heterozygous
      for the common duplication and p.Ile454IlefsX2, and one patient was homozygous
      for p.Arg319X.

PMID- 15979920
TI  - [Chordomas of the base of the skull and upper cervical spine. 100 patients
      irradiated by a 3D conformal technique combining photon and proton beams].
AB  - OBJECTIVE: To define prognostic factors for local control and survival in 100
      consecutive patients treated by fractionated photon and proton radiation for
      chordoma of the skull base and upper cervical spine. PATIENTS AND METHODS:
      Between December 1995 and August 2002, 100 patients (median age: 53 years, range:
      8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons
      and protons. The proton component was delivered by the 201 MeV proton beam of the
      Centre de Protontherapie d'Orsay (CPO). The median total dose delivered to the
      gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A
      complete surgery, incomplete surgery or a biopsy was performed before the
      radiotherapy in 16, 75 and 9 cases, respectively. RESULTS: With a median follow
      up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local
      control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According
      to multivariate analysis, less than 95% of the tumour volume encompassed by the
      95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less
      than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic
      factors of local control. Ten patients died. The 2 and 5-year overall survival
      rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate
      analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely
      independent favourable prognostic factor for overall survival. CONCLUSION: In
      chordomas of the skull base and upper cervical spine treated by surgical
      resection followed by high-dose photon and proton irradiation, local control is
      mainly dependent on the quality of radiation, especially dose-uniformity within
      the gross tumour volume. Special attention must be paid to minimise underdosed
      areas due to the close proximity of critical structures and possibly escalate
      dose-constraints to tumour targets in future studies, in view of the low toxicity
      observed to date.

PMID- 15979921
TI  - Effects of different inter-implant distances on the stress distribution around
      endosseous implants in posterior mandible: a 3D finite element analysis.
AB  - PURPOSE: The aim of this study was to evaluate the effects of different inter
      implant distances on stress distribution in the bone around the endosseous
      titanium implants under vertical, oblique and horizontal loads in the posterior
      mandibular edentulousim by finite element analysis (3D FEA). MATERIALS AND
      METHODS: 3D FEA models representing mandible and ITI implant (Straumann,
      Waldenburg, Switzerland) were simulated. The distances in-between the units were
      set at 0.5, 1.0 and 2.0 cm. Vertical (V) 70 degrees N, 60 degrees oblique (BL) 35
      degrees N in buccolingual direction and horizontal (MD) 14 degrees N in
      mesiodistal direction loads were applied to each of these designs. The principal
      stresses (tensile and compressive stress) on each model were calculated using MSC
      MARC finite element analyze solver software. RESULTS: The tensile stress (P(max))
      values have been evaluated that they rose at the cervical region of buccal side
      when the inter-implant distances increased under V and BL loads and they
      diminished while the inter-implant distances decreased. In short inter-implant
      distances the compressive stress (P(min)) has been presented with increased
      values and found at the lingual surface of the cervical region. DISCUSSION: The
      results of this study indicated that the magnitude of the stress was influenced
      by complex factors such as the direction of loads and the distance between
      adjacent fixtures. The stress occurring around fixtures differs significantly
      with various types of inter-implant distance. CONCLUSION: The evaluation of
      tensile and compressive stresses for cortical and cancellous bone under V, MD and
      BL loading conditions in aspect of inter-implant distance shows; the 1.0 cm of
      inter-implant distance is the optimum distance for two fixture implantation.

PMID- 15979922
TI  - Oncostatin M induces proliferation of human adipose tissue-derived mesenchymal
      stem cells.
AB  - Interleukin-6 (IL-6) subfamily of cytokines, including oncostatin M (OSM),
      leukemia inhibitory factor (LIF), and IL-6, has been implicated in a variety of
      physiological responses, such as cell growth, differentiation, and inflammation.
      In the present study, we demonstrated that both OSM and LIF stimulated the
      proliferation of human adipose tissue-derived mesenchymal stem cells (hATSCs),
      however, IL-6 had no effect on cell proliferation. OSM treatment induced
      phosphorylation of ERK, and pretreatment with U0126, a MEK inhibitor, prevented
      the OSM-stimulated proliferation of hATSCs, suggesting that the MEK/ERK pathway
      is involved in the OSM-induced proliferation. Treatment with OSM also induced
      phosphorylation of JAK2 and JAK3, and pretreatment of the cells with WHI-P131, a
      JAK3 inhibitor, but not with AG490, a JAK2 inhibitor, attenuated the OSM-induced
      proliferation of hATSCs. Furthermore, OSM treatment elicited phosphorylation of
      STAT1 and STAT3, and pretreatment with WHI-P131 specifically prevented the OSM
      induced phosphorylation of STAT1, without affecting the OSM-induced
      phosphorylation of ERK and STAT3. These results suggest that two separate
      signaling pathways, such as MEK/ERK and JAK3/STAT1, are independently involved in
      the OSM-stimulated proliferation of hATSCs.

PMID- 15979923
TI  - Alterations in the intestinal glycocalyx and bacterial flora in response to oral
      indomethacin.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), used extensively in clinical
      medicine, tend to cause adverse effects in the gastrointestinal tract. Earlier
      work has shown that oral administration of indomethacin produced oxidative damage
      in the small intestine and attenuation of the glycocalyx layer of the mucosa. The
      present study assessed, in greater detail, the alterations produced in the
      glycocalyx of rat small intestinal mucosa in response to indomethacin, with
      specific reference to surfactant-like particles (SLP) and brush border membranes
      (BBM). Changes in gut flora in response to the drug were also studied, as it has
      been shown that luminal bacteria play a role in the pathogenesis of NSAID-induced
      intestinal damage. The levels of sugars such as sialic acid, fucose, hexose and
      hexosamine were increased in SLP and decreased in the BBM following indomethacin
      treatment, with the effects being maximal 24h after the administration of the
      drug. The composition of lipids in the SLP was also found to be altered. There
      was a significant increase in the number of bacteria in the luminal contents of
      the small intestine and caecum in these animals, as compared with controls. The
      number of bacteria adherent to the intestinal mucosa was also significantly
      higher in the drug-treated group. In vitro studies revealed that there was an
      increased tendency for bacteria to adhere to SLP isolated from indomethacin
      treated rats. These results suggest that alterations in glycosylation of SLP and
      BBM in response to indomethacin, along with qualitative and quantitative changes
      in the luminal bacterial flora, may facilitate translocation of bacteria into the
      mucosa. These changes may contribute to the enteropathy observed as a result of
      NSAID treatment.

PMID- 15979924
TI  - Smads and chromatin modulation.
AB  - Smad proteins are critical intracellular effector proteins and regulators of
      transforming growth factor type beta (TGFbeta) modulated gene transcription. They
      directly convey signals that initiate at ligand-bound receptor complexes and end
      in the nucleus with changes in programs of gene expression. Activated Smad
      proteins seem to recruit chromatin modifying proteins to target genes besides
      cooperating with DNA-bound transcription factors. We survey here the current and
      still emerging knowledge on Smad-binding factors, and their different mechanisms
      of chromatin modification in particular, in Smad-dependent TGFbeta signaling.

PMID- 15979925
TI  - A role for axon guidance receptors and ligands in blood vessel development and
      tumor angiogenesis.
AB  - Nerves and blood vessels resemble each other in their ability to form branching
      networks. They are in close proximity suggesting possible molecular interactions.
      The patterning of nerves and blood vessels are not random but are regulated by
      attractive and repulsive cues. Four major neuronal guidance factors that are
      sensed by growth cones have been identified, Semaphorin, Ephrin, Slit and Netrin,
      and their cognate receptors, neuropilin, Eph, roundabouts (Robo) and
      uncoordinated-5 (UNC5). Unexpectedly, these ligand/receptor pairs also regulate
      developmental and tumor angiogenesis. Together, there is strong evidence that
      development of the nervous and vascular systems are regulated by common cues.

PMID- 15979926
TI  - Radiation caries--radiogenic destruction of dental collagen.
AB  - Radiogenic dental damage is thought to be the result of reduced salivary flow as
      well as possible direct radiogenic damage. The exact nature of the latter is
      still to be elucidated. We set out to assess whether there was measurable direct
      and immediate radiogenic damage to the collagen component of dental hard and soft
      tissues. A total dose of 31.5 Gy was applied to 40 human third molar teeth in
      vitro (cobalt 60, 6.3 Gy/day for 5 days) (group 1), 40 further third molar non
      irradiated human teeth served as controls (group 2). Collagen fragments (split
      collagen) of mineralized tissue (a) and pulpal tissue (b) of groups 1 and 2 were
      isolated by ultrafiltration and pooled separately for each experimental group.
      Measurement of the mature collagen cross-links hydroxylysylpyridinoline (HP) and
      lysylpyridinoline (LP) by high performance liquid chromatography (HPLC) was used
      to determine the ratio of the amount of collagen fragments from irradiated as
      opposed to non-irradiated teeth and assessing mineralized from pulpal tissue
      separately. No significant difference was found between the concentration of
      collagen cross-links in probes of mineralized tissue between groups 1 and 2. The
      concentration of HP and LP in probes of irradiated dental pulp however was
      significantly increased (ratio: 3.4 and 3.4 times) as compared to pooled probes
      from non-irradiated pulp. Irradiation does not measurably affect the collagen
      component in mineralized dental tissue, which may be due to the relatively low
      concentration of this protein in dentin and enamel. In contrast, direct and
      instant radiogenic damage of (extracellular matrix) pulpal tissue collagen could
      be demonstrated.

PMID- 15979927
TI  - Treatment of Gorham's disease with zoledronic acid.
AB  - Gorham's disease (GD) is a rare disorder characterized by spontaneous and
      progressive osteolysis of one or more bones and thought to belong to
      lymphangiomatoses spectrum of diseases. Surgical, radiation and medical therapies
      have been performed with variable and often discouraging outcomes and currently
      there is no recognized effective treatment. In this paper we describe a 24-year
      old girl with GD localized to mandible who was effectively managed with
      zoledronic acid, a nitrogen-containing high-potency bisphosphonate.

PMID- 15979928
TI  - Expression of TIMP-1 and -2 in different growth patterns of adenoid cystic
      carcinoma.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are special inhibitors of matrix
      metalloproteinases. To evaluate their roles in adenoid cystic carcinoma (ACC), we
      compared TIMP-1 and -2 mRNA and protein expression in different histological
      pattern of ACC. We obtained carcinoma cells from each of cribriform and tubular
      pattern of ACCs using by laser microdissection (LM), to determine the mRNAs
      expression of TIMP-1 and -2 using by real-time quantitative reverse transcription
      polymerase chain reaction (RT-PCR), and to confirm expression of them by
      immunohistochemical staining. Our results showed that mRNA expression of TIMP-1
      tended to be decreased in cribriform pattern compared with tubular pattern in
      four cases, and TIMP-1 significantly decreased in three cases. TIMP-2 also
      significantly decreased in cribriform than in tubular pattern in three of four
      cases. Protein expression of TIMP-1 and -2 decreased in the cribriform pattern
      compared to tubular pattern. These results indicate that there is close
      relationship between TIMPs and growth patterns of ACC, and TIMP-1 and -2 may play
      important roles in morphogenesis and biological character of adenoid cystic
      carcinoma.

PMID- 15979929
TI  - Incidence of oral, pharyngeal, and laryngeal squamous cell carcinomas among 1515
      patients after liver transplantation.
AB  - The purpose of this study was to evaluate the incidence and basic characteristics
      of oral, pharyngeal, and laryngeal squamous cell carcinomas (OPLC) in a single
      centre series of liver transplantations (LT). The medical records of 1515 LT
      cases with a median follow-up of 6 years were analysed retrospectively for
      incident cases of OPLC. Incidence rates for the oral cavity and pharynx (ICD-9:
      141-149), and larynx (ICD-9: 161) were assessed separately. OPLC cases and non
      cases were evaluated with regard to end-stage alcoholic liver disease (ALD) as LT
      indication, smoking, and immunosuppression. The cumulative incidence of 13 cases
      with OPLC was 0.86% in total (n=1515). For 11 cases of OPLC in 307 patients with
      LT for ALD, it was 3.58%. The estimates for the annual incidence of OPLC (ICD-9:
      141-149) were 121.79 for females and 111.65 for males (/100.000 patient-years).
      For OPLC (ICD-9: 161), the estimate was 37.21 for males, respectively (no female
      cases). ALD (84.6%) and pre-LT smoking (92.3%) were significantly overrepresented
      in OPLC cases (p<0.001). Age and gender distribution were comparable to non
      cases. The 5-year survival rate after OPLC was 41.5%. OPLC were demonstrated as a
      late-onset complication of LT with poor prognosis. The impact of pre-, post-LT
      smoking, and, in particular, ALD as a confounder of OPLC deserves further
      investigation.

PMID- 15979930
TI  - Clinicopathological and immunohistochemical study of 39 cases of Adenomatoid
      Odontogenic Tumour: a multicentric study.
AB  - Adenomatoid Odontogenic Tumour (AOT) is a relatively uncommon odontogenic lesion
      and few studies describing its cytokeratin profile have been reported in the
      English-language literature. Thirty-nine cases of AOT from three Oral Diagnosis
      services (Brazil, Mexico and Guatemala) were studied, considering their clinical,
      radiographic, and histological features and immunohistochemical expression of
      cytokeratins (AE1/AE3, 34betaE12, CK1, CK5, CK6, CK7, CK8, CK10, CK13, CK14,
      CK16, CK18, and CK19), vimentin and Ki-67. Sixty five percent of cases affected
      women, anterior maxilla was the preferred site and radiographically most cases
      showed unilocular radiolucency with well defined sclerotic borders. Calcifying
      epithelial odontogenic tumour (CEOT)-like areas were found in 36 out of 39 cases,
      and 10 cases showed positivity for Congo red in polarized light. All cases were
      positive for AE1/AE3, 34betaE12, CK5, CK14 and CK19. CEOT-like areas were
      negative for CK 19. Vimentin was also expressed in 27 cases and this profile may
      indicate the existence of a variable phenotype in certain areas of the tumour.
      There were no recurrences after surgical treatment, and this can be related to
      the low proliferative activity observed in all cases with Ki-67 marker.

PMID- 15979931
TI  - Management of the N0 neck--reference or preference.
AB  - For patients with squamous cell carcinoma of the upper aerodigestive tract,
      appropriate management of the regional lymph nodes is an important and often
      controversial issue that has significant influence on survival. Over the years
      radical treatment either by surgery or radiotherapy contributed to improvement in
      prognosis. Recently, a more conservative approach has achieved a similar level of
      cancer control with less morbidity. This review considers the issues of selection
      of patients for treatment of the neck, choice of modality and extent of therapy,
      treatment of the contralateral neck, management of recurrence and influence of
      the site and status of the primary lesion.

PMID- 15979932
TI  - The biology of restriction and anti-restriction.
AB  - The phenomena of prokaryotic restriction and modification, as well as anti
      restriction, were first discovered five decades ago but have yielded only
      gradually to rigorous analysis. Work presented at the 5th New England Biolabs
      Meeting on Restriction-Modification (available on REBASE, http://www.rebase.com)
      and several recently published genetic, biochemical and biophysical analyses
      indicate that these fields continue to contribute significantly to basic science.
      Recently, there have been several studies that have shed light on the still
      developing field of restriction-modification and on the newly re-emerging field
      of anti-restriction.

PMID- 15979933
TI  - Morphometric analysis of four species of Eubothrium (Cestoda: Pseudophyllidea)
      parasites of salmonid fish: an interspecific and intraspecific comparison.
AB  - Four species of the genus Eubothrium (E. crassum, E. fragile, E. rugosum and E.
      salvelini) were subjected to morphometric comparison. Discriminant analysis was
      conducted utilising 17 characters measured on the scolex and strobila of 101
      specimens. Univariate statistics were first used to detect features that were
      useful for separating individual Eubothrium species and two different host
      populations of E. salvelini. Subsequent multivariate discriminant analysis,
      combining all the measured variables, made it possible to separate all four
      species. A comparison of the four taxa revealed that (1) E. fragile is the most
      distinct species, possessing a much smaller scolex than the other congeners, and
      its similarity with the other marine species E. crassum is not proven; (2) the
      two freshwater taxa, E. rugosum and E. salvelini are the most similar; (3) the
      characters most suitable for species differentiation are the length of the
      scolex, the width of the apical disc, the width of the neck and its area, the
      width of eggs and the number of testes; (4) the width of the apical disc was
      confirmed to be the most stable character at the intraspecific level (within E.
      salvelini host populations) and is therefore considered to be a trait of the
      highest discriminative power in the subset of four Eubothrium species.

PMID- 15979934
TI  - Reanalysis of the protocol for in vitro synchronization of mammalian astrocytic
      cultures by serum deprivation.
AB  - Serum starvation of astrocytes for a period of time followed by refeeding has
      been proposed as a method to produce synchronized astrocytes. Here, it is
      proposed that the method neither synchronizes cells nor satisfies rigorous
      criteria for cell synchronization. The proposed non-selective, whole-culture
      synchronization protocol cannot, in theory, synchronize cells. The cells produced
      by the proposed serum starvation/refeeding protocol do not reflect the properties
      of any particular cell during the cell cycle. Cells produced by the published
      protocol will have a wide distribution of cell sizes, and therefore, the cells
      produced by starvation/refeeding will not model cells of any specific age during
      the division cycle. Thus, the proposed protocol will not produce a synchronized
      culture.

PMID- 15979935
TI  - Spectral studies of coordination compounds of cobalt(II) with thiosemicarbazone
      of heterocyclic ketone.
AB  - The paper presents the spectral analysis of cobalt(II) complexes with indoxyl
      thiosemicarbazone (ITSC) of general composition [CoL2X2] (where L=ITSC, X=Cl-,
      NO3-, (1/2)SO4(2-), NCS-). The geometry of the complexes have been characterized
      by elemental analysis, molar conductance, magnetic susceptibility measurements
      and spectral (electronic, IR, EPR, 1H NMR, mass) studies. The various physico
      chemical techniques suggested a coordination number of six (octahedral) for
      chloro, nitrato and thiocyanato complexes. Whereas sulfato complex was found to
      have five coordinate trigonal-bipyramidal geometry. All the complexes are of high
      spin type showing magnetic moment corresponding to three unpaired electrons.

PMID- 15979936
TI  - The relationship between acidic activation and microstructural changes in
      montmorillonite from Heping, China.
AB  - The montmorillonite sample from Heping, China had been studied by chemical
      analysis, XRD, IR, AFM and MAS NMR. The results showed that acid concentration
      had much influence on surface structure of montmorillonite. When the acid
      concentration reached 2M, the Q3Si structure in silica-oxygen tetrahedron
      recombined, some Q3Si structure in montmorillonite transformed to distortion Q3Si
      structure and Q4Si structure. However, the structure of Al had no changes,
      according with the observation results of atomic force microscope. The Bronsted
      acid site of montmorillonite increases with the accretion of the concentration of
      acid activation, while oversize concentration of acid activation will decrease
      the surface site of montmorillonite.

PMID- 15979937
TI  - Evaluation of existing district health management information systems a case
      study of the district health systems in Kenya.
AB  - INTRODUCTION: This paper discusses some of the issues and challenges of
      implementing appropriate and coordinated District Health Management Information
      System (DHMIS) in environments dependent on external support especially when
      insufficient attention has been given to the sustainability of systems. It also
      discusses fundamental issues which affect the usability of DHMIS to support
      District Health System (DHS), including meeting user needs and user education in
      the use of information for management; and the need for integration of data from
      all health-providing and related organizations in the district. METHODS: This
      descriptive cross-sectional study was carried out in three DHSs in Kenya. Data
      was collected through use of questionnaires, focus group discussions and review
      of relevant literature, reports and operational manuals of the studied DHMISs.
      RESULTS: Key personnel at the DHS level were not involved in the development and
      implementation of the established systems. The DHMISs were fragmented to the
      extent that their information products were bypassing the very levels they were
      created to serve. None of the DHMISs was computerized. Key resources for DHMIS
      operation were inadequate. The adequacy of personnel was 47%, working space 40%,
      storage space 34%, stationery 20%, 73% of DHMIS staff were not trained,
      management support was 13%. Information produced was 30% accurate, 19% complete,
      26% timely, 72% relevant; the level of confidentiality and use of information at
      the point of collection stood at 32% and 22% respectively and information
      security at 48%. Basic DHMIS equipment for information processing was not
      available. This inhibited effective and efficient provision of information
      services. CONCLUSIONS: An effective DHMIS is essential for DHS planning,
      implementation, monitoring and evaluation activities. Without accurate, timely,
      relevant and complete information the existing information systems are not
      capable of facilitating the DHS managers in their day-today operational
      management. The existing DHMISs were found not supportive of the DHS managers'
      strategic and operational management functions. Consequently DHMISs were found to
      be plagued by numerous designs, operational, resources and managerial problems.
      There is an urgent need to explore the possibilities of computerizing the
      existing manual systems to take advantage of the potential uses of microcomputers
      for DHMIS operations within the DHS. Information system designers must also
      address issues of cooperative partnership in information activities, systems
      compatibility and sustainability.

PMID- 15979938
TI  - Occipital intermittent rhythmic delta activity only following eye closure in
      atypical CNS Salmonellosis.
AB  - OBJECTIVE: A statement recently published on the base of a large retrospective
      analysis, report that the occipital intermittent rhythmic delta activity (OIRDA)
      "is associated with epilepsy but not acute encephalopathy" [Gullapalli and
      Fountain. J Clin Neurophysiol 2003;20:35-41]. Our aim is to report, the exception
      from a child with an intermittent fever, in which the finding of an occipital
      intermittent rhythmic delta activity (OIRDA) following the eye closure in the EEG
      recording was the first clinical sign addressing to a CNS involvement. METHODS:
      To review the record from a five-year-old girl with a normal basal
      electroencephalogram and OIRDA that only appeared following eye closure. RESULTS:
      We found OIRDA associated with atypical CNS Salmonellosis. Brain MRI and CSF
      examination confirmed an acute encephalopathy, which was due to Salmonella
      infection. The only symptoms of the infection were episodes of nightly fever that
      had lasted for four weeks, sometimes associated with headache and vomiting. Both
      OIRDA only induced by eye closing and other symptoms disappeared after starting
      antimicrobial therapy. CONCLUSIONS: OIRDA only following eye closure is a non
      specific abnormality and the present findings, based on a single case, merely
      indicate that intracranial infection is among the possible causes. SIGNIFICANCE:
      The new clinical association is certainly worth recording, as the presence of
      this electrophysiological sign may provoke clinicians to then delve further into
      a diagnostic work up.

PMID- 15979939
TI  - Vestibular-evoked extraocular potentials produced by stimulation with bone
      conducted sound.
AB  - OBJECTIVE: To investigate the origin, whether ocular or extraocular, of the short
      latency frontal potential (N15) reported by following vestibular stimulation.
      METHODS: Fourteen subjects with low VEMP thresholds (V(T)) and 9 patients with
      vestibular or ocular disorders were stimulated at the mastoid with bone-conducted
      tone bursts (500 Hz, 8 ms) above vestibular threshold, using a B71 bone vibrator.
      Surface potentials were recorded from Fpz and around the eyes and referred to
      linked earlobes. RESULTS: The N15 was present at Fpz, but was largest around the
      eyes (mean amplitude 2.6 microV, peak latency 13.4 ms, with stimulation at +18 dB
      above threshold) and was generally in phase above and below the eyes. The
      response was vestibular-dependent and modulated by alteration of gaze direction.
      The potentials were delayed in a patient with Miller Fisher syndrome and were
      larger in patients with superior canal dehiscence than in controls. CONCLUSIONS:
      We report a new vestibular-evoked extraocular potential. Its properties are not
      consistent with an eye movement. It is likely to be produced, mainly or
      exclusively, by synchronous activity in extraocular muscles (i.e. a myogenic
      potential). SIGNIFICANCE: Vestibular-evoked extraocular potentials extend the
      range of vestibular pathways that can be assessed electrophysiologically, and may
      be a useful additional test of vestibular function.

PMID- 15979940
TI  - Learning to react: anticipatory mechanisms in children and adults during a
      visuospatial attention task.
AB  - OBJECTIVE: To investigate the mechanisms underlying age-related improvement in
      response times during forewarned motor tasks, using reaction times (RTs) and
      event-related potentials (ERPs) during a variant of the Posner paradigm. METHODS:
      Children and adults reacted to visual targets preceded by a spatial cue. RESULTS:
      As expected, adults responded faster than children whatever the cue-target
      combination, but this advantage could not be explained by differences in
      attentional orienting to, or detection of, target stimuli. ERP differences
      between children and adults corresponded almost exclusively to the period
      preceding target stimuli, where adults, but not children, exhibited a slow
      negative wave that extended from the delivery of the cue to slightly beyond the
      presentation of the target. CONCLUSIONS AND SIGNIFICANCE: The timing, morphology
      and topography of this slow negativity corresponded to those of 'Contingent
      Negative Variation' and 'Readiness Potential' processes. We argue that the
      relative slowness of motor reactions in children during this task was not due to
      a deficit in spatial orienting or target evaluation, but rather to a failure in
      developing anticipatory and preparatory reactions in response to cues, i.e. a
      deficit in executive functions.

PMID- 15979941
TI  - Taking the Myc is bad for Theileria.
AB  - It is commonly acknowledged that intracellular parasites manipulate the survival
      pathways of the host cells to their own ends. Theileria are masters of this
      because they invade bovine leukocytes and immortalize them. Host-cell survival
      depends on the presence of live parasites, and parasite death results in the
      leukocyte undergoing programmed cell death. The parasite, therefore, activates
      several anti-apoptotic pathways in host cells to ensure its own survival. In B
      cells that are infected by Theileria parva, one of the main mechanisms involves
      the induction of c-Myc and the subsequent activation of the anti-apoptotic
      protein Mcl-1. Activation of Myc might occur in other types of leukocyte that are
      infected by Theileria and in other host cells that are infected with different
      parasites.

PMID- 15979942
TI  - Antigen-specific CD8+ T lymphocytes generated from a DNA vaccine control tumors
      through the Fas-FasL pathway.
AB  - Human papillomavirus, particularly type 16, and its oncogenic proteins, E6 and
      E7, are consistently expressed in most cervical cancers. One of the major issues
      facing cancer immunotherapy is that many human cancers evade the immune system by
      downregulating the expression of Fas molecules. An E7-expressing murine tumor
      model with a downregulated Fas expression--TC-1 P3(A15) tumors--was created. A
      DNA vaccine encoding calreticulin linked to E7 (CRT/E7) was able to generate
      protective and therapeutic antitumor effects against TC-1 P3(A15) tumors. In
      vitro Ab depletion and in vivo adoptive experiments showed that the antitumor
      effect of E7-specific CD8+ T lymphocytes against the TC-1 P3(A15) tumor cells was
      through the Fas-FasL-dependent CTL effector mechanism, and the TC-1 P3(A15) tumor
      cells needed higher numbers of antigen-specific CD8+ T lymphocytes for in vivo
      elimination. Our results demonstrated that chimeric CRT/E7 DNA vaccine resulted
      in control of tumors with downregulated Fas expression, highlighting the
      importance of the Fas-FasL pathway in the potent antitumor effect of antigen
      specific CD8+ cytotoxic T lymphocytes and the role of Fas as part of in vivo
      tumor evasion.

PMID- 15979943
TI  - AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a neurodegenerative disorder
      caused by mutations in the gene encoding the lysosomal enzyme palmitoyl protein
      thioesterase-1 (PPT1). The earliest clinical sign in INCL is blindness, followed
      by seizures, cognitive deficits, and early death. Little is known about the
      progression of the visual deficits in INCL. Here we characterize the progressive
      retinal dysfunction and examine the efficacy of AAV2-mediated ocular gene therapy
      in the murine model of INCL. Significant decreases in both mixed rod/cone and
      pure cone electroretinographic amplitudes were observed at as early as 2 months
      of age. Intravitreal injection of AAV2-PPT1 increased enzyme levels in the eye to
      greater than normal levels. The increased PPT1 activity correlated with
      improvements in the histological abnormalities as well as both mixed rod/cone and
      pure cone functions. We also demonstrated that palmitoyl protein thioesterase-1
      activity was detected in the brain following intravitreal injection. The brain
      activity is likely due to anterograde axonal transport along the optic tracts.
      Interestingly, the degree of neurodegeneration throughout the visual pathways of
      the brain was greatly reduced in AAV-treated INCL mice. Therefore, intravitreal
      AAV-mediated gene therapy has direct benefits to the eye and to distal sites in
      the brain along the visual pathways.

PMID- 15979944
TI  - Psychiatric morbidity, quality of life, and disability in mesial temporal lobe
      epilepsy patients before and after anterior temporal lobectomy.
AB  - Considerable interest has been focused on the psychiatric complications of
      medically refractory temporal lobe epilepsy (TLE) before and after epilepsy
      surgery. The aim of the present study was to evaluate the psychiatric status,
      quality of life, and level of disability in medically refractory mesial temporal
      lobe epilepsy (MTLE) patients, a homogenous subgroup of patients with TLE, before
      and after anterior temporal lobectomy (ATL). The study population consisted of 22
      patients with medically refractory MTLE who were candidates for ATL. Patients
      were examined before surgery as well as in the third and sixth months of the
      postoperative period. Psychiatric diagnosis was determined by using SCID-I. To
      rate the severity of psychiatric disorders, BPRS, HDRS, and HARS were employed on
      each visit. WHO-DAS-II and WHOQOL-BREF were used to determine the level of
      disability and quality of life. Preoperatively, six patients had a psychiatric
      diagnosis. Three months after surgery, six of the patients had psychiatric
      diagnoses. Five of these six patients had not been previously diagnosed. There
      was no significant difference between preoperative and postoperative follow-up
      evaluations in terms of HDRS, HARS, and BPRS ratings. With respect to the total
      scores and domains of WHO-DAS-II, the change in pre- and postoperative
      evaluations was statistically significant only for the social life attendance
      domain. There was no significant difference in the mean scores on the WHOQOL-BREF
      domains or on the first question about general evaluation of quality of life. For
      the second question on the level of satisfaction with health, the difference
      between the three ratings was statistically significant. Preoperative and
      postoperative rates of psychiatric disorders in our sample were low. While social
      phobia was frequently seen preoperatively, the postoperative period was
      spearheaded by major depressive disorder. The decrease in disability in
      attendance to social life and improvement in the quality of health were in
      concordance with the literature, indicating the positive results of surgical
      treatment of epilepsy on quality of life. This study suggests that surgical
      intervention might be one of the causes of postoperative psychiatric disorders in
      patients with MTLE.

PMID- 15979945
TI  - The relationship between the pharmacology of antiepileptic drugs and human gene
      variation: an overview.
AB  - Individual differences in clinical responsiveness to antiepileptic drugs are due
      to a complex interaction between environmental factors and genetic variation.
      Considerable interest has arisen in exploiting advances in molecular genetics to
      improve drug therapy for epilepsy and many other diseases; however, practical
      application of pharmacogenetics has been difficult to realize. Attempts to define
      gene variants that are associated with therapeutic (or adverse) effects of
      antiepileptic drugs rely currently on the prior identification of candidate genes
      and the subsequent evaluation of the distribution of allelic variants between
      individuals who have a "good" versus a "poor" clinical response. Many factors can
      adversely affect interpretation of such data, and careful consideration must be
      given to the design of genetic association studies involving candidate genes.
      Candidate genes may be identified in a number of ways; however, for studies of
      drugs, application of knowledge derived from basic pharmacology can suggest
      focused and testable hypotheses that are based on the fundamental principles of
      drug action. Thus, studies of genetic variation as they relate to proteins
      involved in antiepileptic drug kinetics and dynamics will identify key
      polymorphisms in endogenous molecules that determine degrees of drug efficacy and
      toxicity. Delineation of these effects in the coming years will promote enhanced
      success in the treatment of epilepsy.

PMID- 15979946
TI  - Components of the cytochrome P450-dependent monooxygenase system and 'NADPH
      independent benzo[a]pyrene hydroxylase' activity in a wide range of marine
      invertebrate species.
AB  - Levels of components of the cytochrome P450 (CYP)-dependent monooxygenase system
      were characterised in microsomes of major biotransformation tissues, or whole
      bodies, of 33 species from six phyla of aquatic invertebrates. The phylogenetic
      distribution of benzo[a]pyrene hydroxylase (BPH) activity in the absence of added
      NADPH (so-called 'NADPH-independent BPH activity') and presence of NADPH was also
      examined. Microsomal protein yield was higher in individual tissues than whole
      tissues. The main components (total CYP and cytochrome b5; NADPH-dependent
      cytochrome c (CYP) reductase, NADH-dependent cytochrome c reductase and NADH
      dependent ferricyanide (b5) reductase activities) were found in most species of
      the Porifera, Cnidaria, Mollusca, Polychaeta, Crustacea and Echinodermata
      examined. The so-called '418-peak' of the carbon-monoxide difference spectrum of
      reduced microsomes was found in all species, indicating the wide distribution of
      this protein. Total CYP levels (pmol mg(-1) protein; mean+/-SEM) were similar in
      molluscs (50+/-7), crustaceans (61+/-11) and echinoderms (56+/-9), with the
      exception of high levels (223-266) in two crustacean species. NADPH-dependent BPH
      activity (pmol min(-1) mg(-1) protein) was found in 32 species, being lowest in
      Porifera and Cnidaria (3-4), intermediate in Mollusca (7.8+/-1.3), and highest in
      Crustacea (25+/-4) and Echinodermata (15+/-4). NADPH-independent BPH activity was
      evident in 13 out of 15 molluscan species examined, with the addition of NADPH
      either stimulating (8 species) or inhibiting (5 species) the activity. NADPH
      independent BPH activity was also seen in two poriferan species and indicated in
      three crustacean species, suggesting that the phenomenon is not solely restricted
      to the Mollusca.

PMID- 15979947
TI  - Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in
      rats lacking CCK-A receptor.
AB  - Peripheral administration of cholecystokinin (CCK)-8 selectively activates
      oxytocin (OXT)-secreting neurons in the supraoptic (SON) and the paraventricular
      nuclei (PVN) with the elevation of plasma OXT level in rats. We examined the
      effects of intravenous (iv) administration of CCK-8 on the neuronal activity of
      hypothalamic OXT-secreting neurons and plasma OXT level in Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of
      the CCK-A receptor gene. In situ hybridization histochemistry (ISH) for c-fos
      mRNA revealed that the expression of the c-fos gene was not induced in the SON,
      the PVN, the nucleus of the tractus solitarius (NTS) and the area postrema (AP)
      30 min after iv administration of CCK-8 (20 and 40 microg/kg) in OLETF rats. In
      Long-Evans Tokushima Otsuka (LETO) rats (controls), c-fos mRNA was detected
      abundantly in those nuclei 30 min after iv administration of CCK-8 (20
      microg/kg). Immunohistochemistry for c-fos protein (Fos) showed that the
      distributions of Fos-like immunoreactivity (LI) were identical to the results
      obtained from ISH. Dual immunostaining for OXT and Fos revealed that Fos-LI was
      mainly observed in OXT-secreting neurons in the SON and the PVN of LETO rats 90
      min after iv administration of CCK-8 (20 microg/kg). Radioimmunoassay for OXT and
      arginine vasopressin (AVP) showed that iv administration of CCK-8 did not cause
      significant change in the plasma OXT and AVP levels in OLETF rats, while iv
      administration of CCK-8 caused a significant elevation of plasma OXT level
      without changing the plasma AVP level in LETO rats. These results suggest that
      peripheral administration of CCK-8 may selectively activate the hypothalamic OXT
      secreting neurons and brainstem neurons through CCK-A receptor in rats.

PMID- 15979948
TI  - Pax2 expression patterns in the developing chick inner ear.
AB  - The fate specification of the developing vertebrate inner ear could be determined
      by complex regulatory genetic pathways involving the Pax2/5/8 genes. Pax2
      expression has been reported in the otic placode and vesicle of all vertebrates
      that have been studied. Loss-of-function experiments suggest that the Pax2 gene
      plays a key role in the development of the cochlear duct and acoustic ganglion.
      Despite all these data, the role of Pax2 gene in the specification of the otic
      epithelium is still only poorly defined. In the present work, we report a
      detailed study of the spatial and temporal Pax2 expression patterns during the
      development of the chick inner ear. In the period analysed, Pax2 is expressed
      only in some presumptive sensory patches, but not all, even though all sensory
      patches show the scattered Pax2 expression pattern later on. We also show that
      Pax2 is also expressed in several non-sensory structures.

PMID- 15979949
TI  - Ku: a multifunctional protein involved in telomere maintenance.
AB  - The DNA-binding protein Ku plays a critical role in a variety of cellular
      processes, including the repair of double-stranded DNA breaks and V(D)J
      recombination. Paradoxically, while Ku is required for double-stranded break
      repair by non-homologous end-joining, in many organisms, Ku is also associated
      with telomeres. Although telomeres are naturally occurring double-stranded DNA
      breaks, one of their first identified functions is to protect chromosomes from
      end-to-end fusions, a process that is promoted by non-homologous end-joining.
      While located at telomeres, Ku appears to play several important roles,
      including: (1) regulating telomere addition, (2) protecting telomeres from
      recombination and nucleolytic degradation, (3) promoting transcriptional
      silencing of telomere-proximal genes and (4) nuclear positioning of telomeres.
      Here, we review the role of Ku at telomeres in the model organism, Saccharomyces
      cerevisiae and compare and contrast it to the roles of Ku at telomeres in other
      organisms.

PMID- 15979950
TI  - The involvement of key DNA repair pathways in the formation of chromosome
      rearrangements in embryonic stem cells.
AB  - It is vital that embryonic stem (ES) cells, which give rise to the diverse
      tissues of the mature organism, maintain genetic stability. To understand
      mechanisms for the prevention and causation of chromosomal instability, we have
      used spectral karyotyping (SKY) to analyse ES cells from wild-type and repair
      gene knockout mice. We chose cells deficient in Ku70 (DNA end joining), Xrcc2
      (gene conversion), Ercc1 (single-strand annealing) and Csb (transcription-coupled
      repair) to represent potentially-important DNA repair pathways, plus an Xpc
      deficient line to examine loss of global nucleotide excision repair (NER).
      Spontaneous and radiation (X-ray or alpha-particle)-induced chromosome changes
      were assessed to measure the influence of different levels of damage severity on
      response. We show that most repair pathways (except for global NER) protect
      against chromosome changes induced by ionizing radiations, while only homology
      dependent pathways protect against spontaneous chromosomal change in ES cells.
      However, for a given level of damage, the prevalence of different types of
      changes alters in the different repair-deficient lines. Thus, loss of Ercc1, Csb
      or Ku70 leads to increased fragment formation, but loss of Xrcc2 promotes
      exchanges between chromosomes. Strikingly, we found that loss of the Csb gene
      function specifically protects ES cells from complex exchanges, suggesting a role
      for transcription-associated events in complex exchange formation.

PMID- 15979951
TI  - Functional assessment of vascular reactivity after chronic intermittent hypoxia
      in the rat.
AB  - We recently developed a model of chronic intermittent hypoxia (CIH) (FiO2 5%, 8
      h/day, 35 days) in the rat that was associated with an increased infarction in
      isolated heart. The aim of the present study was to characterize its functional
      consequences on vasoreactivity. Aorta and carotid artery were studied using organ
      bath technique while mesenteric vascular bed was perfused. In the three vascular
      beds, relaxation to acetylcholine was similar in CIH and control normoxic (NX)
      rats. Contractions to noradrenaline and angiotensin II were similar between CIH
      and NX rats. In contrast, contraction to endothelin-1 was increased by 17% (P <
      0.05) in carotid artery from CIH rats. Indomethacin pre-treatment reduced by 24%
      (P < 0.001) contraction to endothelin-1 in carotid artery from CIH rats only.
      These data suggested that 35-day CIH-exposure induced no change in endothelial
      function of aorta, carotid artery and mesenteric bed. In contrast, CIH-exposure
      induced an increased contractile response to endothelin-1 in carotid artery,
      presumably owing to the release of constrictor cyclooxygenase-derived products.

PMID- 15979952
TI  - In vivo measurements of human oral cavity heat and water vapor transport.
AB  - Oral heat and water vapor transport may play a significant role in maintaining
      airway health. This study intended to develop a technique for measuring heat and
      mass transfer coefficients in the human oral cavity as a function of flow rate. A
      multi-thermocouple probe was developed which simultaneously measures dry and wet
      bulb temperatures at two airstream sites while also measuring three buccal wall
      temperatures. Oral temperature data (airstream and buccal surface) were acquired
      from eight subjects (two females and six males) breathing at varying flow rates
      to calculate transport coefficients. Techniques used to validate probe accuracy
      included correlating experimentally measured heat transfer in a smooth pipe with
      theoretical plug flow in a circular conduit. Experimental results suggest that
      modeling the oral cavity as a circular conduit is problematic because Nu measured
      in a heated pipe differs so greatly from Nu measured in the oral cavity.

PMID- 15979953
TI  - Capillary electrophoresis of glutathione to monitor oxidative stress and response
      to antioxidant treatments in an animal model.
AB  - Glutathione plays a central role in metabolism and antioxidant defence. Several
      factors can influence the analytical efficiency and rapidity of the quantitative
      determination of glutathione. Procedures in sample pre-treatment have been
      compared in order to minimize analytical errors. Capillary electrophoresis has
      been chosen as a more adequate technique for obtaining a rapid and simple method
      for glutathione and glutathione disulfide determination in the blood and liver of
      the rat. The methods, once optimised, have been validated and applied for
      monitoring the oxidative stress in an animal model, such as the rat made diabetic
      by streptozotocin injection, when the animals are treated with antioxidants and
      compared with the corresponding controls.

PMID- 15979954
TI  - Comparison of functional properties of mammalian DNA polymerase lambda and DNA
      polymerase beta in reactions of DNA synthesis related to DNA repair.
AB  - DNA polymerase lambda (Pol lambda) is a novel enzyme of the family X of DNA
      polymerases. Pol lambda has some properties in common with DNA polymerase beta
      (Pol beta). The substrate properties of Pol lambda were compared to Pol beta
      using DNAs mimicking short-patch (SP) and long-patch (LP) base excision repair
      (BER) intermediates as well as recessed template primers. In the present work,
      the influence of several BER proteins such as flap-endonuclease-1 (FEN1), PCNA,
      and apurinic/apyrimidinic endonuclease-1 (APE1) on the activity of Pol lambda was
      investigated. Pol lambda is unable to catalyze strand displacement synthesis
      using nicked DNA, although this enzyme efficiently incorporates a dNMP into a one
      nucleotide gap. FEN1 and PCNA stimulate the strand displacement activity of Pol
      lambda. FEN1 processes nicked DNA, thus removing a barrier to Pol lambda DNA
      synthesis. It results in a one-nucleotide gapped DNA molecule that is a favorite
      substrate of Pol lambda. Photocrosslinking and functional assay show that Pol
      lambda is less efficient than Pol beta in binding to nicked DNA. APE1 has no
      influence on the strand displacement activity of Pol lambda though it stimulates
      strand displacement synthesis catalyzed with Pol beta. It is suggested that Pol
      lambda plays a role in the SP BER rather than contributes to the LP BER pathway.

PMID- 15979955
TI  - TNFalpha, IFNgamma and IL-10 gene polymorphisms in a sample of Sicilian patients
      with coeliac disease.
AB  - BACKGROUND: Coeliac disease is associated with DQ2 and DQ8 alleles, but other
      genes also confer an additional genetic risk. AIMS: Defining whether the genetic
      profiles of interleukin-10, tumour necrosis factor alpha and interferon gamma are
      associated with an increased coeliac disease risk. PATIENTS AND METHODS: The
      functionally gene polymorphisms of tumour necrosis factor alpha (-308G/A),
      interferon gamma (+874T/A) and interleukin-10 (-1082G/A) were typed using
      sequence specific primer-polymerase chain reaction in 110 Sicilian coeliac
      disease patients and in 220 Sicilian healthy controls. RESULTS: No differences in
      genotype frequencies of interleukin-10 polymorphisms were found between coeliac
      disease patients and healthy controls. A significant increase of -308A (p<0.033;
      OR: 1.72; CI: 1.27-2.33) and of +874T (p: 0.0045; OR: 3.02; CI: 1.47-6.21) allele
      frequencies, both in hetero- and homozygosis, was observed in coeliac patients in
      comparison with healthy controls. In addition, simultaneous significant higher
      percentages of -308A and +874T alleles (p: 0.0066; OR: 2.33; CI: 1.42-3.82) as
      well as simultaneous significant lower percentages of -308A and +874T alleles (p:
      0.003; OR: 0.23; CI: 0.10-0.60) were observed in coeliac patients compared with
      healthy controls. CONCLUSIONS: Genetically determined higher frequencies of -308A
      tumour necrosis factor alpha and +874T interferon gamma alleles, both in hetero
      and in homozygosis and mostly whether simultaneous, may play a role in
      predisposing to gluten intolerance. Subjects positive for -308A tumour necrosis
      factor alpha and +874T interferon gamma alleles have an increased risk for
      coeliac disease.

PMID- 15979956
TI  - [Clinical research of genetic counseling].
AB  - To supply reliable materials for the assessment of recurrence risk,prenatal
      diagnosis and the supervision of high risk persons,we analyzed 10811 patients
      with the methods of cytogenetics,fluorescent in situ hybridization and molecular
      genetic PCR methods. The result of cytogenetics:there were 555 abnormal
      karyotypes of peripheral blood on 5390 cases (10.30%);In 2171 patients who asked
      for prenatal diagnosis,145 abnormal karyotypes were found (6.68%);We also
      karyotyped chorionic villous cells of 62 patients with spontaneous abortion and
      found 28 abnormal karyotypes (45.16%). The PCR results of 23 patients with Down's
      syndrome were all positive while the results of 155 normal persons were all
      negative. The method of cytogenetics is very important for diagnosis of abnormal
      karyotypes;Molecular genetic methods by PCR and FISH are quick,convenient and
      applicable way.

PMID- 15979957
TI  - [Genetic polymorphism of 9 STR loci in Chaoxian National Minority of China].
AB  - In order to enrich the Chinese genetic database,nine polymorphic loci of STR,such
      as D3S1358,vWA,FGA,TH01,TPOX,CSF1PO,D5S818,D13S317 and D7S820 were studied. Based
      on STR gene scan marked by fluorescence,91 unrelated Chinese Chaoxian individuals
      were observed.81 alleles and 196 genotypes were found. The corresponding gene
      frequency and genotype frequency were 0.0055-0.4615 and 0.0110-0.9890
      respectively. The genogypes frequency of nine STR loci was good with the Hardy
      Weinberg equilibrium (P approximately 0.05). The statistical analysis of nine STR
      loci showed the following: PIC (polymorphic information content) >or=0.6863, H
      (heterozygosity) >or=0.6919, DP (discrimination power) >or=0.8301, EPP
      (probability of paternity exclusion) >or=0.8590. The data studied can be used in
      Chinese population genetic studies and forensic medicine applications.

PMID- 15979958
TI  - [Genetic polymorphisms of human short tandem repeat vWA].
AB  - We researched the genetic polymorphisms of vWA in Henan population and its
      usefulness in forensic science.DNA extracted from non-relative persons in Henan
      population with Chelex was amplified by polymerase chain reaction and was typed
      by nondenaturing polyacrylamide gel electrophoresis silver staining.A total of 8
      alleles and 19 genotypes were found in Henan population,its heterozygosity is
      high and the locus can be used in forensic genetics. We obtained the allelic
      frequency of the locus vWA in Henan population. The results of amniotic
      fluid,villus,blood stain indicate vWA is a good locus for forensic study.

PMID- 15979960
TI  - [Genetical investigation on a rare genealogy of congenital camptodactyly].
AB  - Introduced a rare genealogy of autosomal dominant inheritance disease, which
      cardinal signs were congenital camptodactyly and functional disturbance of the
      proximal interphalangeal joints of the II, III, IV, V fingers. Part cases had
      congenital high myopia.

PMID- 15979959
TI  - [Establishment and preservation of immortal lymphoblastoid cell lines of the 10
      ethnic groups in China].
AB  - The immortal lymphoblastoid cell lines were established by EBV transformation of
      B cells and addition of cyclosporin A to inhibit the activity of T cells. In the
      present study,549 immortal cell lines of different ethnic groups of Hazak,
      Manchu, Korea, Hozhe, Mongolia, Sibe, Hui, Puyi, Han in Fujian and Han in Sichuan
      were established. Through our research,we found it is harmful for B lymphocytes
      to transform if excessful leucocytes are inoculated.And it is crisis that
      cyclosporine A shoud be added the last. Our work is an important part of the
      research of human genome diversity for the exploration of the origin and
      evolution of different ethnic groups,and it also provides enough research
      materials for further studies.Moreover,we have sent 50 cell lines of Hozhe,
      Mongolia, Sibe, Daur, Oroqen to CEPH. Thus it is possible for us to utilize the
      genetic resources of CEPH freely.

PMID- 15979961
TI  - [Study on the single nucleotide polymorphisms of the porcine LHbeta gene].
AB  - SSCP analysis was commanded on the whole sequence of porcine LHbeta gene except
      the upstream control region. No polymorphic site was found in the 3 exons and 3'
      control region. But there were 2 polymorphic sites in the 1367 site of intron 1
      and 1823 site of intron 2. The gene frequencies of the 2 sites in the
      Erhualian,Yorkshire and Landrace populations were analyzed.

PMID- 15979962
TI  - [Optimization of parameters of exogene transfection of bovine fetal fibroblasts
      in vitro mediated by liposome].
AB  - pEGFP-C1 eucaryon expression vector was successfully transfected by liposome into
      bovine fetal fibroblasts. We investigated the effect of parameter such as the
      dose of DNA and liposome,number of cell transfected and exposure time of the cell
      to the DNA-liposome complexes. It was indicated that GFP (green fluorescent
      protein) expression was enhanced as the dose of DNA and liposome increased and on
      decline as the exposure time was prolonged. The improvement of transfection
      efficiency depent on the suitable cell number.

PMID- 15979963
TI  - [Experimental results on enterotoxigenic E.coli F18 receptor genotypes].
AB  - A total of 158 pigs of Yorkshire, Landrace and Duroc were selected from some
      swine breeding farms in Hunan province. The genotypes of enterotoxigenic E.coli
      F18 receptor were tested by PCR-RFLP. The results showed that the frequency of
      resistant genotype AA was 0.11,the frequencies of susceptibility genotype AG and
      GG were 0.35 and 0.54 respectively.

PMID- 15979964
TI  - [Inheritance of head and neck color and black hoof of Boer goat].
AB  - The inheritance of head and neck color and black hoof of Boer goats and their
      offspring were analyzed by observing,breeding data and statistic test in the
      Crossbreeding and Improving Research Center of Boer goat in Qinhuangdao city. The
      results indicated that the color of head and neck and black hoof of Boer goat
      were all controlled respectively by two linked recessive genes on one autosome.
      The rate of crossing-over between the genes of head and neck color and black hoof
      was 7.5 genetic units.

PMID- 15979965
TI  - [Studies of effects of lipid on rat fetal neural stem cells].
AB  - Rat fetal neural stem cells (rFNSCs) was separated from embryo about 14.5-16.5
      days, and cultured in DMEM/F12 media with additives and epidermal growth factor
      (EGF) and basic fibroblast growth factor (bFGF). Effects of lipid on growth and
      proliferation of rFNSCs was examined by counting the number of neurospheres and
      incorporation of 3H. The data show that chemical defined lipid improved rFNSCs'
      growth and cell division. Lipid will be another neural stem cell's culture
      media's additive.

PMID- 15979966
TI  - [Screening of the genes in controlling heart development of Drosophila].
AB  - It is becoming increasingly evident that remarkable similaries of heart
      development are revealed in Drosophila and vertebrate, therefore Drosophila can
      be used as a prototype to explore the vertebrate. This can in accelerate to
      revealing of the machanisms of human heart development. In order to screen and
      clone new genes that control the heart development,we have established the
      balanced-lethal lines by chemical mutagen and performed the heart-specific
      antibody. Ten of lines showed mutant phenotype,of which 6 were determined the
      smaller genetic sites for gene location.

PMID- 15979967
TI  - [Studies of the phenotypic character and consanguinity of isozymes in species and
      population].
AB  - Using discontinuous polyacrylamide gel electrophoresis and histochemistry
      methods, lactate and esterase isozyme of three species and five popalation of
      Lacertiformes were analysed. The interspecific zymogramatic differences are
      obvious. Each species possesses its specific zymogram. According to the
      zymogramatic similarity among these species calculated with the method of polar
      ordination,they can be grouped into 2 categories. Gekko chinensis and the two
      population of Gekko subpalmatus fall into one category. The second category
      contains the two population of Hemidactylus bowringii. The congsanguinity of the
      species and popalation has been drawn from the results.

PMID- 15979968
TI  - [Expression and purification of telomerase resever transcriptase motifs in
      E.coli].
AB  - Our project is designed to clone a 1.3kb gene fragment of telomerase catalytic
      subunit gene which contains seven reverse transcriptase motifs and specific
      region with conserved sequence termed "T motif". The gene fragment was amplified
      by PCR and was inserted into expression vector pET28-b. The recombinant plasmid
      was induced by IPTG for 4h and a 52KD recombinant protein was produced. Amount of
      hTRT recombinant protein expression was 20% of total bacterial protein in the
      form of inclusion. Inclusion was dissolved in 8 mol/L urea and 10 mmol/L DTT and
      carried out affinity purification under denaturing condition. The purified hTRT
      recombinant protein was conformed by Western-blot successfully.

PMID- 15979969
TI  - [Construction and expression of recombinant human thymosin alpha1 fusion gene in
      Pichia pastoris].
AB  - The human Thymosin alpha1 (hTalpha1) gene was synthesized according to the
      optimal codons of Pichia pastoris and was fused in 5' terminal of ribosomal
      protein (RP) gene using over lapping polymerase chain reaction. The fusion gene
      was inserted into expression vector of pPIC3. 5K and was transformed into HIS4
      mutant strain GS115 by electroporation. Both SDS-PAGE and Western blot indicated
      that this fusion protein was expressed. The expression level was about 25mg/L.

PMID- 15979970
TI  - [REP-PCR analysis of Helicobacter pylori clinical strains].
AB  - Helicobacter pylori strains isolated from 20 gastritis patients and 20 peptic
      ulcer patients was genotyped by REP-PCR and was clustered with SAS software.
      These strains are divided into two categories according to their genotype. But
      the rate of the two sources of strain in the two categories shows no apparent
      difference(P approximately 0.1), indicating that there is no significant close
      relationship between the genotype and the pathogenicity.

PMID- 15979971
TI  - [Discussion of learning and instructional strategies on genetics teaching].
AB  - This paper attempts to explore learning and teaching strategies, such as,
      attention, classification, organization, provoke-thinking,problem-solving,and
      learning-based task analysis and programmed teaching strategies in genetics
      teaching on the basis of the concept of lifelong education and struggle for
      existence. It aims at teaching students how to study and at the same time improve
      teaching efficiency.

PMID- 15979972
TI  - [The double helix model of DNA structure--the physical nature of the gene].
AB  - In 1953, Watson and Crick set forth their hypothesis for the double-helical
      nature of DNA. The Watson-Crick model had an immediate effect on the emerging
      discipline of molecular biology. It was a remarkable feat and highly significant
      in the history of genetics and biology.

PMID- 15979973
TI  - [Progress in researches on neural tube defects related the genes].
AB  - Neural tube defects are common birth defects which are ascribed to the
      combination of genetic and environmental factors. The genetic factors include
      cell growth factors,transformation factors and key enzymic genes involved in
      folate metabolism. This paper reviews the genes as focus of current investigation
      and the relationship between the genetic polymorphism on the specific sites and
      neural tube defects based on animal model and population epidemiological study.
      It indicates that the multifactors play an important role in the etiology of
      neural tube defects.

PMID- 15979974
TI  - [The fast TnT isoforms specifically expressed in avian adult pectoral muscles of
      Galliforms and physiological significance].
AB  - Three homologous genes have evolved to encode the cardiac,slow and fast skeletal
      muscle troponin Ts(TnTs) in the vertebrate. Multiple isoforms in each type of TnT
      are generated through alternative mRNA splicing during the development and the
      modality of the fast skeletal TnT isoforms is the most complex. The TnT isoforms
      specifically expressed in avian adult fast skeletal muscle (especially in the
      adult pectoral muscle) of Galliforms have been characterized as follows: 1. There
      exist a cluster of transition metal ion binding sites [generally 4-7 repeats of a
      sequence motif His-(Glu/Ala)- Glu-Ala-His, designated as Tx] in the NH2-terminal
      variable region. 2. Compared with mammalian TnT and the neonatal or young avian
      TnT, these avian pectoral muscle TnTs prefer to express exon 16 in the COOH
      terminal variable region. Furthermore,possible effects of the pectoral fTnT
      isoforms on the physiological activity are discussed in this article.

PMID- 15979975
TI  - [Progress on gene targeting].
AB  - Gene targeting is a rising technology in molecular biology,which is defined as
      the introduction of exogeneous DNA to specific site in genome by homologous
      recombination,and consequently change the hereditary character of the cell. This
      technology provides a new and powerful means for research in developmental
      biology,molecular genetics,immunology and medicine. Progresses have been made in
      exploring gene structure and function,gene expression and regulation,transgene
      and gene therapy with the application of gene targeting. But there are some
      problems in gene targeting,especially for the low efficiency. This article just
      provided a review of the principle and program of gene targeting,and discussed
      the possible approaches to increase the efficiency of gene targeting.

PMID- 15979976
TI  - [MHC and its application in the population and conservation genetics].
AB  - The major histocompatibility complex (MHC),with the highest genetic
      polymorphism,is a cluster of genes involved in immune response regulation in the
      vertebrates.MHC can provide information such as population genetic
      diversity,evolutionary history and population dynamics,and population genetic
      structure etc. It can also be applied in the captive breeding programme for
      endangered vertebrate species.

PMID- 15979977
TI  - [Advances on the plant disease resistant beta-glucanase gene].
AB  - Study of beta-1,3-glucanase is one of the hot points in plant genetic engineering
      of disease resistance,big progress has been made in the past few years. This
      paper briefly reviewed the main biological characters and mechanism involved in
      the disease resistance,the classification,structure,function and the
      transformation of beta-1,3-glucanase genes.

PMID- 15979978
TI  - [A novel approach to study pathogenesis of pathogens in vivo--signature-tagged
      mutagenesis].
AB  - Signature-tagged mutagenesis (STM) is a novel approach to study pathogenesis of
      pathogens and to screen virulence genes with high throughput in vivo,which is
      based on whole genome of pathogen in question. In recent years, more than ten
      species of microbial pathogens have been screened with this technology. There are
      also unknown virulence factors being identified with exception of known virulence
      genes identified in all these screens. This article reviews the principle,
      advantages and current limitations,the requirements, modifications of STM, and to
      date virulence genes identified by this technology.

PMID- 15979979
TI  - [Microsatellite markers and applications in the barley genome].
AB  - Microsatellites, also called simple sequence repeats (SSR), are simple, tandemly
      repeated DNA sequences with a repeat length of a few base pairs,and are very
      ideally used as molecular markers because of their abundance, high level of
      polymorphism, co-dominance and ease of assay with the polymerase chain reaction
      (PCR) by selecting primers as the conserved DNA sequences flanking the SSRs,as
      well as better stability. The experiments showed that SSRs are randomly
      distributed throughout the barley genome,and there are 3-18 alleles at a single
      SSR locus,up to 37 alleles/locus. SSR markers have being widely applied in the
      construction of molecular genetic map, the study of genetic diversity,the
      identification of germplasm, gene mapping for important traits and molecular
      marker-assisted selection. Meanwhile,most of markers are strongly clustered
      around the centromeric regions of all seven linkage groups. As a result of the
      clustering,genome coverage with SSRs remains incomplete with an obvious lack of
      markers on the long arms of chromosomes 1H and 5H and short arm of chromosome 6H.
      Therefore,it is very potential and necessary to further develop SSR markers in
      barley.

PMID- 15979980
TI  - [The meaning of epigenetics].
AB  - Epigenetics, the term was introduced by Conrad H.Waddington, in 1942,he said that
      to compare genetics with epigenetics, the study of the processes by which
      genotype gives rise to phenotype. In 1987, Robin Holliday redefined epigenetic as
      "Nuclear inheritance which is not based on differences in DNA sequence". The
      author of this paper introduced that in Science,10 August 2001,there was a
      special collection of review articles focused on the topic of epigenetics. The
      new "histone code" hypothesis states that the highly modifiable amino termini
      could carry their own combinatorial codes to help control phenotype,and that part
      of this code is heritable. And in light of this hypothesis,researchers are
      approaching further possibilities in human biology and types of cancer and other
      diseases.

PMID- 15979981
TI  - Comparison of label-free methods for quantifying human proteins by shotgun
      proteomics.
AB  - Measurements of mass spectral peak intensities and spectral counts are promising
      methods for quantifying protein abundance changes in shotgun proteomic analyses.
      We describe Serac, software developed to evaluate the ability of each method to
      quantify relative changes in protein abundance. Dynamic range and linearity using
      a three-dimensional ion trap were tested using standard proteins spiked into a
      complex sample. Linearity and good agreement between observed versus expected
      protein ratios were obtained after normalization and background subtraction of
      peak area intensity measurements and correction of spectral counts to eliminate
      discontinuity in ratio estimates. Peak intensity values useful for protein
      quantitation ranged from 10(7) to 10(11) counts with no obvious saturation
      effect, and proteins in replicate samples showed variations of less than 2-fold
      within the 95% range (+/-2sigma) when >or=3 peptides/protein were shared between
      samples. Protein ratios were determined with high confidence from spectral counts
      when maximum spectral counts were >or=4 spectra/protein, and replicates showed
      equivalent measurements well within 95% confidence limits. In further tests,
      complex samples were separated by gel exclusion chromatography, quantifying
      changes in protein abundance between different fractions. Linear behavior of peak
      area intensity measurements was obtained for peptides from proteins in different
      fractions. Protein ratios determined by spectral counting agreed well with those
      determined from peak area intensity measurements, and both agreed with
      independent measurements based on gel staining intensities. Overall spectral
      counting proved to be a more sensitive method for detecting proteins that undergo
      changes in abundance, whereas peak area intensity measurements yielded more
      accurate estimates of protein ratios. Finally these methods were used to analyze
      differential changes in protein expression in human erythroleukemia K562 cells
      stimulated under conditions that promote cell differentiation by mitogen
      activated protein kinase pathway activation. Protein changes identified with
      p<0.1 showed good correlations with parallel measurements of changes in mRNA
      expression.

PMID- 15979982
TI  - Regulation of photosystem I reaction center genes in Synechocystis sp. strain PCC
      6803 during Light acclimation.
AB  - Cyanobacteria acclimate to changes in incident light by adjusting photosystem
      stoichiometry through regulation of PSI accumulation. To gain a deeper insight
      into this control mechanism in Synechocystis sp. strain PCC 6803, we studied the
      expression and regulation of the psaAB operon, encoding the reaction center
      proteins of PSI, during the initial stage of acclimation to changes in the
      intensity and quality of light. The psaAB operon was transcribed as a dicistronic
      transcript, which was processed into smaller, putatively monocistronic psaA and
      psaB transcript species. Dark treatment of the cells inhibited the psaAB
      transcription, whereas re-illumination of dark-adapted cells reactivated the
      transcription slowly in a process requiring de novo protein synthesis. Transfer
      of cells from white to orange light, favoring excitation of PSII, stimulated the
      psaAB transcription, whereas far-red light, primarily exciting PSI, down
      regulated the transcription of the psaAB operon. These results, together with
      down-regulation of psaAB transcription upon the addition of electron transport
      inhibitors under constant white light illumination, suggested that the
      photosynthetic redox poise affects the psaAB transcription activity in the light.
      Pulse-labeling experiments demonstrated that light-induced modulations in the
      translation rate of the PsaA protein closely parallel the transcription rate of
      the psaAB operon, indicating that transcriptional regulation plays the major role
      in determining the content of PSI reaction center proteins and, thereby, PSI
      complexes, during light acclimation. The scantiness of PsaA translation in
      darkness despite the abundance of psaA transcripts demonstrated that the
      comprehensive regulation of PSI accumulation also involves regulation at the
      level of translation.

PMID- 15979983
TI  - Dissection of the phosphorylation of rice DELLA protein, SLENDER RICE1.
AB  - DELLA proteins are repressors of gibberellin signaling in plants. Our previous
      studies have indicated that gibberellin signaling is derepressed by SCF(GID2)
      mediated proteolysis of the DELLA protein, SLENDER RICE1 (SLR1), in rice. In
      addition, the gibberellin-dependent increase of phosphorylated SLR1 in the loss
      of-function gid2 mutant suggests that the SCF(GID2)-mediated degradation of SLR1
      might be initiated by gibberellin-dependent phosphorylation. To confirm the role
      of phosphorylation of SLR1 in its gibberellin-dependent degradation, we revealed
      that SLR1 is phosphorylated on an N-terminal serine residue(s) within the
      DELLA/TVHYNP and polyS/T/V domain. However, gibberellin-induced phosphorylation
      in these regions was not observed in the gid2 mutant following the constitutive
      expression of SLR1 under the control of the rice actin1 promoter. Treatment with
      gibberellin induced both the phosphorylated and non-phosphorylated forms of SLR1
      with similar induction kinetics in gid2 mutant cells. Both the phosphorylated and
      non-phosphorylated SLR1 proteins were degraded by gibberellin treatment with a
      similar half-life in the rice callus cells, and both proteins interacted with
      recombinant glutathione S-transferase (GST)-GID2. These results demonstrate that
      the phosphorylation of SLR1 is independent of its degradation and is dispensable
      for the interaction of SLR1 with the GID2/F-box protein.

PMID- 15979985
TI  - On the European Union's new eastern border: health promotion, HIV and Ukraine.
AB  - HIV control in Ukraine is a pressing public health challenge and national efforts
      to control the epidemic have been hindered by a lack of capacity and resources.
      One component of control is the need to raise awareness. Implementing a health
      promotion strategy through the education system and through multi-sector network
      with early stakeholder ownership resulted in a limited budget being spent
      principally on production costs rather than purchasing media time and space with
      considerable savings. Early involvement of powerful corporate stakeholders in
      multi-disciplinary teams has the potential to enhance the effectiveness and
      efficiency of health promotion measures in a post-Soviet transitional economy.

PMID- 15979984
TI  - Diagnostic value of C reactive protein in infections of the lower respiratory
      tract: systematic review.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of C reactive protein in
      detecting radiologically proved pneumonia and to evaluate how well it can
      discriminate between bacterial and viral infections of the lower respiratory
      tract. DATA SOURCES: Medline and Embase (January 1966 to April 2004), with
      reference checking. STUDY SELECTION: We included articles comparing C reactive
      protein with a chest radiograph or with microbiological work-up as a reference
      test. Two authors independently assessed methodological items. RESULTS: None of
      the studies met all validity criteria. Six studies used an infiltrate on chest
      radiograph as reference test. Sensitivities ranged from 10% to 98%, specificities
      from 44% to 99%. For adults, the relation of C reactive protein with an
      infiltrate (in a subgroup analysis of five studies) showed an area under the
      curve of 0.80 (95% confidence interval 0.75 to 0.85). In 12 studies, the relation
      of C reactive protein with a bacterial aetiology of infection of the lower
      respiratory tract was studied. Sensitivities ranged from 8% to 99%, specificities
      from 27% to 95%. These data were epidemiologically and statistically
      heterogeneous, so overall outcomes could not be calculated. CONCLUSION: Testing
      for C reactive protein is neither sufficiently sensitive to rule out nor
      sufficiently specific to rule in an infiltrate on chest radiograph and bacterial
      aetiology of lower respiratory tract infection. The methodological quality of the
      diagnostic studies is generally poor. The evidence not consistently and
      sufficiently supports a wide introduction of C reactive protein as a rapid test
      to guide antibiotics prescription.

PMID- 15979986
TI  - Sex ratio at birth and war in Croatia (1991-1995).
AB  - BACKGROUND: We have investigated sex ratio at birth (expressed as the proportion
      of males) in Croatia before, during and after the war (1991-1995). METHODS: Data
      for each of 21 counties in Croatia (861 516 births) were collected and pooled
      into two groups: the first, consisting of the counties unaffected by the war, and
      the second, comprising the counties affected by war events. Odds ratios of being
      born as a male were calculated, with being born in a county exposed to war
      defined as the risk factor. RESULTS: No significant deviations from the expected
      ratio of 0.514 were found in pre-war, wartime or post-war period at the national
      level. The ratio was 0.515 during the pre-war and wartime periods, and 0.514 in
      the post-war period. Comparison of the ratios in the three periods in both
      affected and unaffected counties revealed no significant increase in the sex
      ratio. The only significant increase in the sex ratio was registered in two
      counties unaffected by the warfare. CONCLUSIONS: This study indicates that
      warfare did not cause a detectable increase of the sex ratio at birth in Croatia,
      in contrast to what might have been predicted based on earlier reports in the
      literature.

PMID- 15979987
TI  - Ovarian stromal blood flow in the prediction of ovarian response during in vitro
      fertilization treatment.
AB  - BACKGROUND: This study evaluated the role of ovarian stromal blood flow in the
      prediction of the ovarian response of infertile women by comparing age of women,
      body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and
      ovarian stromal blood flow indices measured by power Doppler in two-dimensional
      ultrasound. Patients were aged <40 years with basal FSH <10 IU/l on recruitment
      for IVF treatment. METHODS: All received a standard regimen of ovarian
      stimulation in their first IVF cycle. AFC, pulsatility index, resistance index
      and peak systolic blood flow velocity of ovarian stromal vessels were determined
      on the second day of the treatment cycle prior to ovarian stimulation. Ovarian
      response was represented by the number of oocytes, serum oestradiol, and the
      duration and dosage of gonadotrophins. RESULTS: A total of 136 women were
      included in the analysis. Basal FSH concentration achieved the best predictive
      value in relation to the number of oocytes obtained, followed by AFC and BMI. AFC
      was the only predictive factor of serum oestradiol concentration on the day of
      HCG while BMI was predictive of the gonadotrophin dosage. CONCLUSION: Ovarian
      stromal blood flow indices measured by power Doppler ultrasound had no predictive
      value for the ovarian response.

PMID- 15979988
TI  - Expectant, medical or surgical treatment for spontaneous abortion in first
      trimester of pregnancy: a cost analysis.
AB  - BACKGROUND: Misoprostol and expectant care have been shown to be acceptable
      alternatives to routine surgical evacuation for treatment of spontaneous abortion
      in the first trimester of pregnancy. The objective of this study was to analyse
      the cost of expectant care, misoprostol therapy and surgical evacuation. METHODS:
      A decision tree was designed to simulate the clinical outcome and health care
      resource utilization of surgical evacuation, misoprostol and expectant care for
      patients presenting with uncomplicated spontaneous abortion in the first
      trimester of pregnancy. Clinical inputs were estimated from literature and the
      cost analysis was conducted from the perspective of a public health care provider
      in Hong Kong. RESULTS: The base-case analysis showed that the misoprostol group
      (1000 US dollars per patient) was the least costly alternative, followed by the
      expectant care (1172 US dollars per patient) and surgical evacuation (2007 US
      dollars per patient). Rates of complete abortion using misoprostol and expectant
      care were identified as influential factors. Monte Carlo simulation (10000
      cohorts) showed that the misoprostol and the expectant care groups were less
      costly than the surgical evacuation group 100 and 88% of the time. The
      misoprostol group was less costly than the expectant group 100% of the time.
      CONCLUSIONS: Misoprostol therapy appears to be the least costly approach for
      treatment of uncomplicated spontaneous abortion.

PMID- 15979989
TI  - Gene expression and immunolocalization of heparin-binding epidermal growth factor
      like growth factor and human epidermal growth factor receptors in human corpus
      luteum.
AB  - BACKGROUND: The objective of this study was to elucidate gene expression and
      immunolocalization of heparin-binding epidermal growth factor-like growth factor
      (HB-EGF) and human epidermal growth factor receptor (HER) family in the human
      ovary during luteal growth and regression. METHODS: Ovaries obtained from pre
      menopausal women were used for immunohistochemistry and semiquantitative RT-PCR
      analysis. RESULTS: Immunoreactive HB-EGF was not detected in follicles or oocyte,
      while HB-EGF became apparent in granulosa luteal cells in the early luteal phase,
      and most abundant in the mid-luteal phase, but less abundant in the late luteal
      phase. Immunostaining for HER1 was very weak in granulosa luteal cells in the
      early and mid-luteal phases, and was not detected in the late luteal phase.
      Immunoreactive HER4 was abundant in the early luteal phase and became less
      abundant in the mid-luteal phase, whereas it was negative in the late luteal
      phase. Semiquantitative RT-PCR analysis revealed that HB-EGF and HER1 mRNA levels
      were high in the mid-luteal phase, whereas HER4 mRNA expression was high in the
      early luteal phase. CONCLUSIONS: HB-EGF may play a vital role in regulating
      luteal growth in a juxtacrine manner and through activating HER4 signalling.

PMID- 15979990
TI  - Increased cyclooxygenase-2 expression is associated with better clinical outcome
      in patients submitted to complete ablation for severe endometriosis.
AB  - BACKGROUND: Recent studies have demonstrated the overexpression of cyclooxygenase
      2 (COX-2) in endometriosis. The aim of this study was to investigate the
      correlation between COX-2 expression and the clinical outcome rate in a
      homogeneous series of patients undergoing fertility-sparing complete laparoscopic
      ablation for severe endometriosis. METHODS: COX-2 expression was analysed by
      immunohistochemistry in 103 samples, 71 endometriomas (group 1) and 32 peritoneal
      implants and or recto-vaginal nodules (group 2) of endometriotic tissue from 85
      patients submitted to complete laparoscopic ablation of severe endometriosis.
      RESULTS: At median follow-up of 54 months, a recurrence rate of 24.7% (n = 21)
      was observed. Patients with COX-2-positive endometriotic cysts showed a lower
      relapse rate than COX-2-negative cases (16.7 versus 41.2%; P = 0.036). Patients
      with COX-2-positive peritoneal implant and or recto-vaginal nodule showed a
      similar trend. Taking the two groups of patients together, we found a
      significantly lower relapse rate in COX-2-positive patients in comparison to COX
      2-negative patients (16.4 versus 40%; P = 0.0152). Moreover, COX-2-positive
      patients showed a longer relapse-free survival in comparison to COX-2-negative
      patients (P = 0.016). CONCLUSIONS: In patients with severe endometriosis who
      underwent fertility-sparing complete ablation, COX-2 overexpression characterizes
      a subgroup of patients with lower risk of relapse and longer relapse-free
      survival.

PMID- 15979991
TI  - Investigation of the infertile couple: a basic fertility work-up performed within
      12 months of trying to conceive generates costs and complications for no
      particular benefit.
AB  - The current approach of the basic fertility work-up has been questioned recently
      in this journal. Based on new data on human fecundity, the authors advocated
      starting the fertility work-up after just 6 months of trying to conceive instead
      of the usual 12 months. In women younger than 39 years and with a regular cycle,
      there are several arguments why the basic fertility work-up should not be done
      earlier than after 12 months of child wish. Firstly, 50% of couples who have
      tried to conceive for 6 months without success will conceive in the next 6 months
      without any treatment. Secondly, the prevalence of fertility diseases is lower in
      couples who have been trying to conceive for 6 months as compared with those who
      have been trying for 12 months. Performance of a fertility work-up at this stage
      will lead to an increase in false-positive diagnoses compared with performing
      them at 12 months of subfertility. Thirdly, fertility treatment will have fewer
      additional effects in couples with good spontaneous conception prospects (6-12
      months child wish), compared with subfertile couples who have poor prospects. At
      present, none of the available fertility treatments have success rates comparable
      with no intervention in these women, and postponement of treatment in such
      couples will prevent complications such as ovarian hyperstimulation syndrome and
      multiple pregnancies. We argue that the fertility work-up should not be offered
      to couples with a duration of child wish of <12 months, except for women with
      ovulation disorders and women of 39 years and older.

PMID- 15979992
TI  - Expression of interleukin-8 and monocyte chemotactic protein-1 in adenomyosis.
AB  - BACKGROUND: To clarify the inflammatory nature of adenomyosis, we aimed to
      investigate the expression of interleukin-8 (IL-8) and monocyte chemotactic
      protein-1 (MCP-1) by immunohistochemistry to determine their putative role in
      pathophysiology of adenomyosis. METHODS: Adenomyosis samples, with their eutopic
      endometrium, were collected from 30 women undergoing hysterectomy. Endometrium
      from 27 women without adenomyosis were also collected as a control group. Samples
      were grouped according to the menstrual cycle phase and examined by
      immunohistochemistry for IL-8 and MCP-1. RESULTS: In normal endometrium,
      secretory phase samples expressed higher levels of epithelial IL-8 than in
      proliferative phase samples (P = 0.01), and we observed a trend for an increased
      epithelial MCP-1 expression in the secretory phase samples compared with the
      proliferative phase samples (P = 0.07). Endometrial samples of women with
      adenomyosis did not show the same cyclic variation. In the secretory phase,
      eutopic endometrium of women with adenomyosis expressed lower levels of
      epithelial IL-8 and MCP-1 compared with normal endometrium (P < 0.05). The
      expression of epithelial IL-8 and MCP-1 was higher in the adenomyosis foci than
      the eutopic endometrium (P < 0.05). CONCLUSIONS: These findings may indicate that
      an intrinsic abnormality of inflammatory response may be present in eutopic
      endometrium of women with adenomyosis, and IL-8 and MCP-1 may contribute to the
      pathophysiology of adenomyosis.

PMID- 15979993
TI  - Sexuality after laparoscopic Davydov in patients affected by congenital complete
      vaginal agenesis associated with uterine agenesis or hypoplasia.
AB  - BACKGROUND: Several surgical techniques have been described for the treatment of
      patients with vaginal agenesis. The simplest intervention that gives good sexual
      results should be the surgical technique of choice. METHODS: We report anatomic
      and functional outcome in 28 women after vaginoplasty using laparoscopic Davydov
      operation. This surgery includes three steps: two laparoscopic and one perineal.
      The patient then has to use a mould or a vaginal dilatator for 1 month. The
      functional outcome was assessed by a brief and valid self-report questionnaire
      evaluating female sexual life (Female Sexual Function Index, FSFI). A control
      group was recruited to compare the results. RESULTS: Two intra-operative bladder
      and ureteric injuries were repaired without sequels. Two post-operative
      complications were observed: one abdominal migration of the mould, which was
      treated successfully with the laparoscope, and one vesico-vaginal fistula. No
      patient was lost to follow-up. The anatomical result was judged to be
      satisfactory (>6 cm) in 26 of the 28 patients: the mean vaginal length was 7.2 +/
      1.5 cm. Among the 28 operated women, 19 had a good or very good result. No
      statistical difference was found between our operated patients and French
      controls in all six domains of the FSFI. CONCLUSIONS: Laparoscopic Davydov may be
      considered a good option for the surgical treatment of women presenting vaginal
      agenesis. This technique offers advantages such as: short operating time and
      hospital stay, no particular instrumentation required and no external scars.
      Sexuality approaches so-called 'normal sexuality'.

PMID- 15979994
TI  - A lower ongoing pregnancy rate can be expected when GnRH agonist is used for
      triggering final oocyte maturation instead of HCG in patients undergoing IVF with
      GnRH antagonists.
AB  - BACKGROUND: Eliciting an endogenous LH surge by GnRH-agonist for the induction of
      final oocyte maturation may be more physiological compared with the
      administration of HCG. However, the efficacy of this intervention in patients
      treated for IVF with GnRH antagonists remains to be assessed. METHODS: 106
      patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg
      Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF
      was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was
      started on stimulation day 6. Luteal phase was supported with micronized vaginal
      progesterone and oral estradiol. The study was monitored continuously for safety
      and stopping rules were established. RESULTS: No significant differences were
      present in the number of cumulus-oocyte complexes retrieved, in the proportion of
      metaphase II oocytes, in fertilization rates or in the number and quality of the
      embryos transferred between the two groups. However, a significantly lower
      probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation
      of the trial, according to the stopping rules established (odds ratio 0.11; 95%
      confidence interval 0.02-0.52). CONCLUSIONS: Lower probability of ongoing
      pregnancy can be expected when GnRH agonist is used for triggering final oocyte
      maturation instead of HCG in patients undergoing ovarian stimulation for IVF with
      GnRH antagonists.

PMID- 15979995
TI  - Presence of membrane and soluble forms of Fas ligand and of matrilysin (MMP-7)
      activity in normal and abnormal human semen.
AB  - BACKGROUND: The aim of this study is to shed some light on the role of the Fas
      system in human semen, by investigating whether there is an association between
      the expression of the molecules regulating the Fas system [membrane-bound Fas
      ligand (mFasL), soluble Fas ligand (sFasL) and matrilysin, the metalloprotease
      cleaving mFasL to sFasL] and sperm parameters. METHODS: We investigated, by flow
      cytometric analysis, the presence of FasL on spermatozoa from normozoospermic and
      teratozoospermic subjects and, by western blot, the presence of sFasL and
      matrilysin in the seminal plasma of the same samples as well as on samples from
      azoospermic subjects. The enzymatic activity of matrilysin was examined by gel
      zymography. RESULTS: We observed that sperm cells expressed mFasL in 22% of
      normozoospermic men, whereas it was absent from spermatozoa from teratozoospermic
      patients. Higher levels of sFasL and augmented enzymatic activity of matrilysin
      were found in azoospermic samples. CONCLUSIONS: The presence of mFasL on sperm
      from normozoospermic men and its absence in pathological samples emphasize the
      role of the Fas system in human semen. Moreover, the presence of both sFasL and
      matrilysin in seminal plasma implies a fine regulation of the function of the Fas
      system and, consequently, of the apoptotic process in the human genital tract.

PMID- 15979996
TI  - ESHRE Task Force on Ethics and Law 10: surrogacy.
AB  - This 10th statement of the Task Force on Ethics and Law considers ethical
      questions specific to varied surrogacy arrangements. Surrogacy is especially
      complex as the interests of the intended parents, the surrogate, and the future
      child may differ. It is concluded that surrogacy is an acceptable method of
      assisted reproductive technology of the last resort for specific medical
      indications, for which only reimbursement of reasonable expenses is allowed.

PMID- 15979997
TI  - Vascular endothelial growth factor gene +405 C/G polymorphism is associated with
      susceptibility to advanced stage endometriosis.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is known to play a pivotal
      role in the development of endometriosis. This study was performed to investigate
      whether the VEGF gene 5'-untranslated region polymorphism is associated with
      susceptibility to advanced stage endometriosis. METHODS: This study comprised 215
      women with advanced stage endometriosis, 219 control women without endometriosis,
      and 70 fertile women. Following extraction of genomic DNA, genotyping of the -460
      C/T and +405 C/G polymorphisms of the VEGF gene were performed by polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP)
      analysis. RESULTS: The distribution of genotypes and allele frequencies of the 
      460 C/T polymorphism in the endometriosis group did not differ from those in the
      control group and the fertile women group. However, genotype distribution of the
      +405 C/G polymorphism was significantly different between patients with and
      without endometriosis (P = 0.01) and between patients with endometriosis and the
      fertile women (P = 0.02). Patients with endometriosis showed a higher incidence
      of the +405 CC genotype compared with the controls and the fertile women (P =
      0.007 and 0.016 respectively). CONCLUSIONS: These findings suggest that the VEGF
      +405 C/G polymorphism may be associated with the risk of advanced stage
      endometriosis in the Korean population.

PMID- 15979998
TI  - Consequences of vanishing twins in IVF/ICSI pregnancies.
AB  - BACKGROUND: Spontaneous reductions are a possible cause of the increased
      morbidity in IVF singletons. The aim of this study was to assess incidence rates
      of spontaneous reductions in IVF/ICSI twin pregnancies and to compare short- and
      long-term morbidity in survivors of a vanishing co-twin with singletons and born
      twins. METHODS: We identified 642 survivors of a vanishing co-twin, 5237
      singletons from single gestations and 3678 twins from twin gestations. All
      children originated from pregnancies detected by transvaginal sonography in
      gestational week 8. By cross-linkage with the national registries the main
      endpoints were prematurity, birth weight, neurological sequelae and mortality.
      RESULTS: Of all IVF singletons born, 10.4% originated from a twin gestation in
      early pregnancy. Multiple logistic regression analyses adjusted for maternal age,
      parity and ICSI treatment showed for birth weight <2500 g an odds ratio (OR) of
      1.7 [95% confidence interval (CI) 1.2-2.2] and for birth weight <1500 g OR 2.1
      (95% CI 1.3-3.6) in singleton survivors of a vanishing twin versus singletons
      from single gestations; corresponding figures were seen for preterm birth. This
      increased risk was almost entirely due to reductions that occurred at >8 weeks
      gestation. We found no excess risk of neurological sequelae in survivors of a
      vanishing co-twin versus the singleton cohort; however, OR of cerebral palsy was
      1.9 (95% CI 0.7-5.2). Furthermore, we observed a correlation between onset of
      spontaneous reduction, i.e. the later in pregnancy the higher the risk of
      neurological sequelae (r = -0.09; P = 0.02). Adjusted OR of child death within
      the follow-up period was 3.6 (95% CI 1.7-7.6) in the survivor versus the
      singleton cohort. CONCLUSIONS: One in 10 IVF singletons originates from a twin
      gestation. Spontaneous reductions that occur at >8 weeks gestation are one of the
      causes for the higher risk of adverse obstetric outcome in IVF singletons.

PMID- 15979999
TI  - Chemokine expression is dysregulated in the endometrium of women using progestin
      only contraceptives and correlates to elevated recruitment of distinct leukocyte
      populations.
AB  - BACKGROUND: Breakthrough bleeding (BTB) is the most common reason for
      discontinuation of progestin-only (p-only) contraceptives, yet the causes are
      unknown. Use of p-only contraceptives is associated with elevated influx of
      endometrial leukocytes, similar to that observed perimenstrually or within
      decidualized endometrium. We hypothesized that chemokine expression is altered in
      women using p-only contraceptives, leading to abnormal leukocyte recruitment and
      BTB. METHODS: Expression of eight highly abundant endometrial chemokines was
      examined using immunohistochemistry and real-time PCR, in endometria from women
      using subdermal and intrauterine levonorgestrel and correlated to leukocyte
      subpopulations. RESULTS: Macrophage-derived chemokine (MDC), hemofiltrate CC
      chemokine-1 (HCC-1), monocyte chemoattractant protein-3 (MCP-3), interleukin-8
      (IL-8) and eotaxin were strongly produced by epithelial glands, comparable to
      levels in premenstrual phase endometrium. Stromal cells were negative for
      chemokines in atrophic/shedding endometria, but intensely positive in highly
      decidualized tissues for MDC, MCP-3, HCC-1 and 6Ckine. Macrophage inflammatory
      protein-1beta (MIP-1b) and HCC-4 were suppressed in all p-exposed endometria.
      CONCLUSIONS: These data demonstrate that chemokine expression is dysregulated in
      p-exposed endometria, consistent with the morphological appearance of the
      endometrium and the leukocyte subsets present. This reinforces a potential role
      for chemokines in the elevated leukocyte recruitment that contributes to
      endometrial fragility and BTB.

PMID- 15980000
TI  - Single embryo transfer is an option in frozen embryo transfer.
AB  - BACKGROUND: A good strategy to decrease multiple pregnancy rate in assisted
      reproduction technology (ART) is the use of single embryo transfer (SET).
      METHODS: This retrospective study analysed 1647 frozen embryo transfers carried
      out during 1998-2003 in Helsinki University Central Hospital; of these, 872 were
      double embryo transfers (DETs) and 775 SETs. The SET group included 140 (18.1%)
      elective SETs (eSETs). RESULTS: The yearly rate of SETs in frozen cycles
      increased from 28 to 66%. Overall, the clinical pregnancy rate per frozen embryo
      transfer was 30.7% and the delivery rate 22.6%. The delivery rate was
      significantly higher in DET cryocycles than in SET cryocycles (25.7 versus 19.2%,
      respectively; P < 0.01). In DET cryocycles, the multiple delivery rate was 21.9%,
      10 times higher than that observed in cryocycles with SET (2.0%) (P < 0.0001).
      When eSET was applied, no difference in delivery rate was observed when compared
      with cryocycles with DET (28.6 and 25.7%, respectively). CONCLUSIONS: SET can be
      used in frozen cycles to reduce multiple delivery rates.

PMID- 15980001
TI  - Associate editor's commentary: mathematical modelling and clinical prediction.

PMID- 15980002
TI  - A new quality-of-life measure for men experiencing involuntary childlessness.
AB  - BACKGROUND: Infertility may considerably reduce quality-of-life. Many of the
      existing generic quality-of-life measures, which often focus on physical
      impairments, do not represent the specific complaints of infertile patients. In
      this article, we report on the development and validation of the TLMK (Tubinger
      Lebensqualitatsfragebogen fur Manner mit Kinderwunsch), an instrument for
      measuring quality-of-life in male patients with involuntary childlessness.
      METHODS: The first version of the questionnaire, which consisted of 91 items, was
      administered to 275 men who attended andrology and gynaecology clinics for
      fertility evaluations. After the questionnaires were scored, item analysis and
      reduction, principal component analysis and internal consistency analyses were
      conducted. RESULTS: The final version of the TLMK consists of 35 items in four
      scales and provides an internally consistent quality-of-life profile for men
      experiencing involuntary childlessness. Convergent and discriminant validity was
      supported through the correlation of the TLMK scales with established
      questionnaires on life satisfaction (FLZ) and partnership (PFB). CONCLUSION: The
      TLMK provides information about the quality-of-life in men experiencing
      involuntary childlessness and was found to be easy to administer and acceptable
      to patients. It may be used to assess patients' baseline and ongoing quality-of
      life during fertility treatment and as an outcome variable in the evaluation of
      integrated psychological counselling.

PMID- 15980003
TI  - Gene deletions in an infertile man with sperm fibrous sheath dysplasia.
AB  - BACKGROUND: Asthenozoospermia may sometimes be related to genetic structural
      defects of the sperm tail detectable by transmission electron microscopy.
      Dysplasia of the fibrous sheath (DFS) is a genetic sperm defect, characterized by
      dysplastic development of the axonemal and periaxonemal cytoskeleton. We report
      the case of an infertile man with normal sperm count and total sperm immotility
      in which dysplasia of the fibrous sheath, Akap3, Akap4 gene deletions, meiotic
      segregation of chromosomes 18, X and Y and Y microdeletions were investigated.
      METHODS: A 32-year-old man with a 3-year history of primary infertility presented
      at our Regional Referral Center for Male Infertility. Family medical history,
      lymphocyte karyotype, PCR analysis, physical examination, hormone assays and
      semen analysis were performed. RESULTS: Ultrastructural sperm evaluation showed
      dysplasia of the fibrous sheath. Immunostaining of AKAP4 protein was negative in
      sperm tails. PCR analysis revealed intragenic deletions of the Akap3 and Akap4
      genes. Fluorescence in situ hybridization on sperm showed a high frequency of XY
      disomy. CONCLUSION: In this infertile patient, our results suggest a possible
      relationship between dysplasia of the fibrous sheath, partial deletions in the
      Akap3 and Akap4 genes and absence of AKAP4 protein in the fibrous sheath. These
      findings, however, were not detected in another four patients with dysplasia of
      the fibrous sheath. Our results require future confirmatory molecular analyses.

PMID- 15980004
TI  - Short-term ischaemic storage of human uterine myometrium--basic studies towards
      uterine transplantation.
AB  - BACKGROUND: Transplantation of the uterus has been suggested as a possible future
      treatment of absolute uterine infertility. The tolerability of human uterine
      tissue to cold ischaemic storage was tested in the present study. METHODS: Small
      tissue samples of human uteri were subjected to cold (4 degrees C) ischaemia (6
      and 24 h) in Ringer acetate (RIN), the intracellular-like University of Wisconsin
      solution (UW) or the extracellular-like Perfadex solution (PER). The ability of
      myometrial strips to contract, histology by light and electron microscopy as well
      as tissue concentrations of glutathione, ATP and protein were used as parameters
      to detect cold ischaemic injuries. RESULTS: Contractile ability and response to
      prostaglandin F(2alpha) (PGF(2alpha)) was better preserved after 6 h cold
      ischaemia in UW and PER in comparison with the other groups. Histological
      examination did not reveal any major changes after 6 and 24 h cold ischaemic
      storage in UW and PER solutions, while specimens stored in RIN for 24 h displayed
      degenerative changes on the electron microscopy level. UW and PER preserved ATP
      concentrations significantly better than RIN. Myometrium stored in UW contained
      more total glutathione but also a larger proportion of oxidized glutathione than
      specimens stored in RIN and PER. Protein concentrations did not change with
      storage time in any of the solutions. CONCLUSIONS: The results show that human
      uterine myometrial tissue is resistant towards cold ischaemia for at least 6 h if
      stored in UW and PER solutions.

PMID- 15980005
TI  - Further evidence on the role of heparan sulfate as protamine acceptor during the
      decondensation of human spermatozoa.
AB  - BACKGROUND: Human spermatozoa decondense in vitro upon exposure to heparin and
      glutathione. Glutathione is also the disulfide bond reducer in vivo, and heparan
      sulfate, a functional analogue of heparin, has been proposed as the protamine
      acceptor. The aim of this study was to evaluate the decondensing ability of
      chemically modified heparins and different glycosaminoglycans (GAGs) on isolated
      sperm nuclei in vitro, and to analyse the possible role of different GAGs as
      protamine acceptors. METHODS: Capacitated spermatozoa and isolated sperm nuclei
      from normospermic semen samples were decondensed in the presence of heparin (or
      its equivalent) and glutathione. After fixation with glutaraldehyde, the
      percentage of decondensed spermatozoa and nuclei was determined under phase
      contrast. Proteins were extracted from sperm nuclei previously incubated in the
      presence of gluhathione and different GAGs by incubation with urea-beta
      meracptoethanol-NaCl, and analysed by acid polyacrylamide gel electrophoresis.
      RESULTS: The ability of desulfated heparins and other GAGs to decondense isolated
      nuclei mirrored exactly the decondensation of capacitated spermatozoa, the only
      difference being the level of maximum decondensation achieved. Heparan sulfate
      and heparin, but not other GAGs, were able to release protamines from sperm
      chromatin. CONCLUSIONS: Heparan sulfate could be functioning as protamine
      acceptor in vivo during human sperm nuclear decondensation.

PMID- 15980006
TI  - Episodic air pollution is associated with increased DNA fragmentation in human
      sperm without other changes in semen quality.
AB  - BACKGROUND: This study examined potential associations between exposure to
      episodes of air pollution and alterations in semen quality. The air pollution,
      resulting from combustion of coal for industry and home heating in the Teplice
      district of the Czech Republic, was much higher during the winter than at other
      times of year with peaks exceeding US air quality standards. METHODS: Young men
      from Teplice were sampled up to seven times over 2 years allowing evaluation of
      semen quality after periods of exposure to both low and high air pollution.
      Routine semen analysis (sperm concentration, motility and morphology) and tests
      for sperm aneuploidy and chromatin integrity were performed, comparing
      measurements within each subject. Exposure was classified as high or low based on
      data from ambient air pollution monitoring. RESULTS: Using repeated measures
      analysis, a significant association was found between exposure to periods of high
      air pollution (at or above the upper limit of US air quality standards) and the
      percentage of sperm with DNA fragmentation according to sperm chromatin structure
      assay (SCSA). Other semen measures were not associated with air pollution.
      CONCLUSION: Exposure to intermittent air pollution may result in sperm DNA damage
      and thereby increase the rates of male-mediated infertility, miscarriage, and
      other adverse reproductive outcomes.

PMID- 15980007
TI  - Outcome of ICSI in HIV-1-infected women.
AB  - BACKGROUND: Since 2001, French law has permitted the use of assisted reproductive
      technology in human immunodeficiency virus (HIV)-1 infected women under strict
      conditions. This report describes a preliminary series of seropositive women who
      underwent assisted reproduction treatment at our facility. To minimize
      contamination of culture media, equipment, and therefore of male gametes and
      embryos, we chose to perform ICSI in all cases. The outcome of ICSI was compared
      with the outcome in an age-matched group of non-HIV-1-infected women. Since
      several previous reports have indicated that HIV infection may be associated with
      a decrease in spontaneous fertility, our goal was also to assess the fertility
      status of the HIV-1-infected women entering our ICSI programme. METHODS: The
      French law governing the use of assisted reproduction protocols in HIV-1-infected
      women was strictly applied. The inclusion criteria were absence of ongoing
      disease, CD4((+)) count >200 cells/mm(3), and stable HIV-1 RNA level. Since mean
      age at the time of ICSI was higher in HIV-1-infected women than in the overall
      group of non-HIV-infected women, we compared outcome data in HIV-1-infected women
      (group I) to a group of non-HIV-1-infected women matched with regard to age and
      follicle retrieval period (group II) as well as to the overall group of women who
      underwent ICSI at our institution (group III). RESULTS: A total of 66 ovarian
      stimulations was performed in 29 HIV-1-infected-infected women. The percentage of
      cancelled cycles was higher in infected women than in matched controls (15.2
      versus 4.9%, P < 0.05). The duration of ovarian stimulation (13.3 versus 11.7
      days, P < 0.05) and amount of recombinant FSH injected (2898 versus 2429 IU, P <
      0.001) were also higher in infected women. The number of retrieved oocytes,
      mature oocytes, and embryos obtained as well as embryo quality was similar in all
      groups. The fertilization rate was higher in infected women than in matched
      controls (67 versus 60%, P < 0.01). The pregnancy rate was not significantly
      different between groups I and II (16.1 versus 19.6%) in spite of the fact that
      the number of embryos transferred was purposefully restricted in the HIV-1
      infected group to minimize multiple pregnancy (2.0 versus 2.4, not significant).
      CONCLUSION: The results of this preliminary series of ICSI cycles in HIV-1
      infected women indicate that optimal ovarian stimulation is slightly more
      difficult to achieve than in matched seronegative women. However, when criteria
      for oocyte retrieval were fulfilled, ICSI results were similar to those of age
      matched controls.

PMID- 15980008
TI  - The combined contraceptive vaginal ring and bone mineral density in healthy pre
      menopausal women.
AB  - BACKGROUND: Hormonal contraceptives have been associated with various effects on
      the bone mineral density (BMD) of pre-menopausal women. The aim of this study was
      to assess the effects of a vaginal contraceptive ring on BMD in pre-menopausal
      women and compare them with those of non-hormonal contraceptive use. METHODS:
      This open-label, multicentre study used dual-energy X-ray absorptiometry to
      measure BMD in the lumbar spine (L(2)-L(4)) and femoral neck regions. Subjects
      were assigned 3:1 to receive a contraceptive ring (n = 105) or a non-hormonal
      contraceptive control (n = 39) and were assessed after 13 and 26 cycles of
      contraceptive ring treatment or 12 and 24 months of control treatment. RESULTS:
      No change from baseline in BMD (Z-scores) was seen in contraceptive ring users (n
      = 73) at either time-point. In the control group (n = 30), BMD increased slightly
      from baseline resulting in significant differences (P < 0.0001) between the two
      groups at cycle 26/month 24. These differences are not clinically relevant,
      although some degree of acquisition of peak bone mass might have been prevented
      in the contraceptive ring group. The contraceptive ring was generally well
      tolerated; a higher incidence of treatment-related adverse events was observed in
      the contraceptive ring group compared with the non-hormonal contraceptive control
      group. CONCLUSIONS: In healthy pre-menopausal women, 2 years of contraceptive
      ring use produced no changes in BMD.

PMID- 15980009
TI  - ICSI outcome in patients with transient azoospermia with initially motile or
      immotile sperm in the ejaculate.
AB  - BACKGROUND: In patients with transient azoospermia, few sperm may be found in the
      ejaculate. We investigated the outcome of ICSI in patients with transient
      azoospermia. METHODS: Records of patients with transient azoospermia referred
      during a 42 month period were reviewed. If only immotile sperm were found, the
      sample was incubated with 30% human serum albumin (HSA) before motility re
      assessment. If still immotile, mechanical assessment of sperm viability was
      utilized. Study groups were: (A) motile sperm; (B) motility achieved by HSA; (C)
      no motility, but viability assessed by a mechanical technique; and (D) control
      group with sperm counts from 1 to 5 x 10(6)/ml. There were 57 couples (cycles) in
      the study group and 43 couples (cycles) in the control group. RESULTS: Age, days
      of stimulation and endometrial thickness were comparable among groups. In 29.8%
      of the cycles, only immotile sperm were found. Fertilization and cleavage rates
      were higher in groups A and D than in groups B and C. Clinical pregnancy
      rate/cycle and live birth rate/cycle were not different among groups. No
      congenital malformations were found in newborns. CONCLUSION: Fertilization and
      cleavage rates were lower in patients with initially immotile sperm compared with
      those with initially motile sperm and oligoasthenoteratozoospermia patients.
      Clinical pregnancy and viable pregnancy rates were not statistically different
      among groups, although when only immotile sperm were present both clinical
      pregnancy and live birth rate were lower in comparison with cycles with motile
      sperm.

PMID- 15980010
TI  - Gynaecological health care utilization and use of sex hormones--the study of
      Health in Pomerania.
AB  - BACKGROUND: In Germany, there is a lack of population-based data related to the
      use of gynaecological health care services. The objectives of our analyses
      utilizing a population-based cross-sectional survey conducted in one
      geographically defined area [Study of Health in Pomerania (SHIP)] are to assess
      the prevalences of: (i) attendance of gynaecological outpatient facilities and of
      (cervical) cancer screening; (ii) gynaecological and breast surgery; (iii) use of
      oral contraceptives (OC) and menopausal hormone therapy (MHT). METHODS: We
      analysed socio-demographic factors, reproductive history, gynaecological service
      utilization, and use of sex hormones in 2186 women aged 20-79 years. We used
      standard statistics and sex- and age group-specific weighting factors to reflect
      characteristics of the population of Western Pomerania. RESULTS: Approximately
      43% of women reported surgical procedures. Participation in cancer screening at
      least once was reported by 78% of women (lifetime prevalence). Two-thirds of
      women stated ever use of OC, 28% (aged >40 years) ever use of MHT. CONCLUSIONS:
      Women in Western Pomerania reported a high life-time use of both OC and MHT. The
      use of cervical cancer screening exceeded the national average. Women had an
      almost 50% risk of undergoing gynaecological, breast or obstetric surgery. The
      high use of MHT and surgical procedures calls for efforts regarding continuing
      medical education and health care policy actions.

PMID- 15980011
TI  - Reassessing the role of progesterone in fertilization--compartmentalized calcium
      signalling in human spermatozoa?
AB  - Progesterone is present at micromolar concentrations in the vicinity of the
      oocyte. Human spermatozoa generate a biphasic rise in intracellular calcium
      concentration ([Ca(2+)](i)) and undergo the acrosome reaction upon progesterone
      stimulation, suggesting that the hormone acts as a secondary inducer or 'primer'
      of the acrosome reaction in association with the zona pellucida. However, the
      sensitivity of human spermatozoa to progesterone is such that many cells may
      undergo the acrosome reaction prematurely, compromising their ability to
      fertilize. We have shown that exposing human spermatozoa to a progesterone
      gradient, simulating the stimulus encountered as sperm approach the oocyte,
      results in a novel response. A slow rise in [Ca(2+)](i) occurs, upon which, in
      many cells, [Ca(2+)](i) oscillations are superimposed. Cells showing this pattern
      of response do not undergo the acrosome reaction, but instead show an alternating
      pattern of flagellar activity associated with peaks and troughs of [Ca(2+)](i). A
      Ca(2+) store in the rear of the sperm head apparently generates this complex
      signal, functioning as an '[Ca(2+)](i) oscillator'. We propose that: (i) the
      acrosome reaction and flagellar beat are regulated by separate Ca(2+) stores;
      (ii) these stores are mobilized through different mechanisms by different
      agonists; and (iii) progesterone in vivo acts as a switch for the oscillator
      which regulates the flagellar beat mode.

PMID- 15980012
TI  - Normal gestations and live births after orthotopic autograft of vitrified-warmed
      hemi-ovaries into ewes.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term outcome of
      autotransplantation of vitrified warmed hemi-ovaries into ewes. METHODS: Six hemi
      ovaries from six ewes aged 6 to 12 months were vitrified. After dissection of the
      medulla, the hemi-ovarian cortex was stored at -196 degrees C in liquid nitrogen.
      Four to six weeks after the first laparotomy, the left ovary was removed and the
      vitrified-warmed hemi-ovary was sutured. RESULTS: Plasma progesterone
      concentration increased in a regular manner in all ewes. Three pregnancies
      occurred, from which four lambs were born. The first delivery of a normal lamb
      occurred in February 2003. The second delivery of two normal lambs occurred in
      March 2003 (a 2.5 kg male and a 2.8 kg female). The last lamb had a normal
      delivery but had a malformation of the left leg and the oesophagus. This lamb
      died two months after delivery from pneumariae. Histological examination of the
      grafted vitrified ovaries showed few primordial and antral follicles.
      CONCLUSIONS: These three pregnancies in a ewe model may indicate that ovarian
      vitrification gives results as good as those from a slow cooling protocol in
      autograft. It is impossible to establish a link between the vitrification
      procedure and the malformation of the last lamb, and further studies are needed
      to evaluate the feasibility of ovarian vitrification.

PMID- 15980014
TI  - ESHRE guideline for the diagnosis and treatment of endometriosis.
AB  - The objective was to develop recommendations for the diagnosis and treatment of
      endometriosis and its associated symptoms. A working group was convened comprised
      of practising gynaecologists and experts in evidence-based medicine from Europe,
      as well as an endometriosis self-help group representative. After reviewing
      existing evidence-based guidelines and systematic reviews, the expert panel met
      on three occasions for a day during which the guideline was developed and
      refined. Recommendations based solely on the clinical experience of the panel
      were avoided as much as possible. The entire ESHRE Special Interest Group for
      Endometriosis and Endometrium was given the opportunity to comment on the draft
      guideline, after which it was available for comment on the ESHRE website for 3
      months. The working group then ratified the guideline by unanimous or near
      unanimous voting; finally, it was approved by the ESHRE Executive Committee. The
      guideline will be updated regularly, and will be made available at
      http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting
      evidence, and the relevant references and abstracts. For women presenting with
      symptoms suggestive of endometriosis, a definitive diagnosis of most forms of
      endometriosis requires visual inspection of the pelvis at laparoscopy as the
      'gold standard' investigation. However, pain symptoms suggestive of the disease
      can be treated without a definitive diagnosis using a therapeutic trial of a
      hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed
      disease, suppression of ovarian function for 6 months reduces endometriosis
      associated pain; all hormonal drugs studied are equally effective although their
      side-effects and cost profiles differ. Ablation of endometriotic lesions reduces
      endometriosis-associated pain and the smallest effect is seen in patients with
      minimal disease; there is no evidence that also performing laparoscopic uterine
      nerve ablation (LUNA) is necessary. In minimal-mild endometriosis, suppression of
      ovarian function to improve fertility is not effective, but ablation of
      endometriotic lesions plus adhesiolysis is effective compared to diagnostic
      laparoscopy alone. There is insufficient evidence available to determine whether
      surgical excision of moderate-severe endometriosis enhances pregnancy rates. IVF
      is appropriate treatment especially if there are coexisting causes of infertility
      and/or other treatments have failed, but IVF pregnancy rates are lower in women
      with endometriosis than in those with tubal infertility. The management of
      severe/deeply infiltrating endometriosis is complex and referral to a centre with
      the necessary expertise is strongly recommended. Patient self-help groups can
      provide invaluable counselling, support and advice.

PMID- 15980013
TI  - Chronic chromium exposure-induced changes in testicular histoarchitecture are
      associated with oxidative stress: study in a non-human primate (Macaca radiata
      Geoffroy).
AB  - BACKGROUND: Reproductive toxicity of chromium is in dispute despite positive
      findings in rodents. Recently we reported epididymal toxicity of hexavalent
      chromium (CrVI) in bonnet monkeys and in this paper we report its testicular
      toxicity. METHODS: Adult monkeys (Macaca radiata) were given drinking water
      containing CrVI (100, 200, 400 p.p.m.) for 6 months and testes were removed for
      ultrastructural and biochemical analyses. RESULTS: CrVI treatment disrupted
      spermatogenesis, leading to accumulation of prematurely released spermatocytes,
      spermatids and uni- and multinucleate giant cells in the lumen of seminiferous
      tubules. Transmission electron microscopy revealed granulation of chromatin and
      vacuolation between acrosomal cap and manchette microtubules of elongated
      spermatids and in the Golgi area of round spermatids. Pachytene spermatocytes had
      fragmented chromatin and swollen mitochondria with collapsed cristae.
      Spermatocytes and spermatogonia in the basal compartment were unaffected.
      Macrophages containing phagocytosed sperm and dense inclusions in Sertoli cells
      were seen. Specific activities of the antioxidant enzymes superoxide dismutase,
      catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate
      dehydrogenase and concentrations of the non-enzymatic antioxidants glutathione,
      vitamins A, C and E decreased, while concentrations of H(2)O(2) and hydroxyl
      radicals increased in the testis of chromium-treated monkeys. Withdrawal of
      chromium treatment for 6 months normalized spermatogenesis and the status of pro-
      and antioxidants in the testis. CONCLUSIONS: CrVI disrupts spermatogenesis by
      inducing free radical toxicity, and supplementation of antioxidant vitamins may
      be beneficial to the affected subjects.

PMID- 15980015
TI  - Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast
      growth factor and ribonuclease-1.
AB  - Human pancreatic ribonuclease-1 (RNase1) does not exhibit its cytotoxicity unless
      it is artificially internalized into the cytosol. Furthermore, once it encounters
      the cytosolic RNase inhibitor (RI), the activity of RNase1 is seriously reduced.
      To achieve the cellular targeting of RNase1 and the blocking of RI binding
      simultaneously, the basic fibroblast growth factor (bFGF) sequence was inserted
      into RNase1 at the RI binding site using a gene fusion technique. The effect of
      this fusion protein, CL-RFN89, on the angiogenesis, which was accelerated by FGF
      FGF receptor interaction, was investigated. It was shown by using fluorescein
      labeled CL-RFN89, that the binding to human umbilical vein endothelial cells
      (HUVECs) was dependent on the existence of the FGF receptors. In addition, CL
      RFN89 inhibited the cellular growth of HUVECs in vitro and also inhibited the
      tube formation, using a three-dimensional tube formation assay. Furthermore, this
      fusion protein was shown to prevent in vivo tumor cell-induced angiogenesis,
      using the mouse dorsal air sac assay. These results demonstrated that CL-RFN89
      inhibits angiogenesis in vitro and in vivo and that it can be expected to be a
      potent antiangiogenic agent.

PMID- 15980016
TI  - Epitope mapping using mRNA display and a unidirectional nested deletion library.
AB  - In vitro selection targeting an anti-polyhistidine monoclonal antibody was
      performed using mRNA display with a random, unconstrained 27-mer peptide library.
      After six rounds of selection, epitope-like peptides were identified that contain
      two to five consecutive, internal histidines and are biased for arginine
      residues, without any other identifiable consensus. The epitope was further
      refined by constructing a high-complexity, unidirectional fragment library from
      the final selection pool. Selection by mRNA display minimized the dominant
      peptide from the original selection to a 15-residue functional sequence (peptide
      Cmin: RHDAGDHHHHHGVRQ; K(D) = 38 nM). Other peptides recovered from the fragment
      library selection revealed a separate consensus motif (ARRXA) C-terminal to the
      histidine track. Kinetics measurements made by surface plasmon resonance, using
      purified Fab (antigen-binding fragment) to prevent avidity effects, demonstrate
      that the selected peptides bind with 10- to 75-fold higher affinities than a
      hexahistidine peptide. The highest affinity peptides (K(D) approximately 10 nM)
      encode both a short histidine track and the ARRXA motif, suggesting that the
      motif and other flanking residues make important contacts adjacent to the core
      polyhistidine-binding site and can contribute >2.5 kcal/mol of binding free
      energy. The fragment library construction methodology described here is
      applicable to the development of high-complexity protein or cDNA expression
      libraries for the identification of protein-protein interaction domains.

PMID- 15980017
TI  - CTKPred: an SVM-based method for the prediction and classification of the
      cytokine superfamily.
AB  - Cell proliferation, differentiation and death are controlled by a multitude of
      cell-cell signals and loss of this control has devastating consequences.
      Prominent among these regulatory signals is the cytokine superfamily, which has
      crucial functions in the development, differentiation and regulation of immune
      cells. In this study, a support vector machine (SVM)-based method was developed
      for predicting families and subfamilies of cytokines using dipeptide composition.
      The taxonomy of the cytokine superfamily with which our method complies was
      described in the Cytokine Family cDNA Database (dbCFC) and the dataset used in
      this study for training and testing was obtained from the dbCFC and Structural
      Classification of Proteins (SCOP). The method classified cytokines and non
      cytokines with an accuracy of 92.5% by 7-fold cross-validation. The method is
      further able to predict seven major classes of cytokine with an overall accuracy
      of 94.7%. A server for recognition and classification of cytokines based on multi
      class SVMs has been set up at http://bioinfo.tsinghua.edu.cn/~huangni/CTKPred/.

PMID- 15980018
TI  - Computational modeling of type I collagen fibers to determine the extracellular
      matrix structure of connective tissues.
AB  - A method is presented for generating computer models of biological tissues. The
      method uses properties of extracellular matrix proteins to predict the structure
      and physical chemistry of the elements that make up the tissue. The method begins
      with Protein Data Bank coordinate positions of amino acids as input into
      TissueLab software. From the amino acid sequence, a type I collagen-like triple
      helix backbone was computationally constructed and boundary spheres were added
      based on known chemical and physical properties of the amino acids. Boundary
      spheres determined the contact surface characteristics of the collagen molecules
      and intermolecular interactions were then determined by considering the
      relationships of the contact surfaces and by resolving the energy-minimum state
      using feasible sequential quadratic programming. From this, the software created
      fibrils that corresponded exactly to known collagen parameters and were further
      confirmed by finite element modeling. Computationally derived fibrils were then
      used to create collagen fibers and three-dimensional collagen matrices. By
      resolving the energy-minimum state, large complex components of the extracellular
      space as well as other structures can be determined to provide three-dimensional
      structure of molecules, molecular interactions and the tissues that they form.

PMID- 15980019
TI  - Anemia and thrombocytopenia in children with Plasmodium vivax malaria.
AB  - Clinico-epidemiological features of pediatric patients with malaria due
      Plasmodium vivax that developed anemia and thrombocytopenia requiring
      hospitalization are herein reported. Over a 3-year period, 78 children with P.
      vivax infection were admitted to our Hospital in Sucre, Venezuela. Clinical
      manifestations at admission were 93.59 per cent fever, 41.03 per cent chills and
      14.10 per cent headache, among others. On paraclinical evaluations 94.87 percent
      presented with anemia (10.26 per cent severe), 25.64 percent with malnutrition,
      and 10.26 percent had intestinal parasitosis. The mean hemoglobin levels on
      admission were 8.09 g/dl and mean platelet counts 127 402 cells/mm3. Among these
      patients 58.97 per cent developed thrombocytopenia (24.36 per cent severe)
      requiring transfusion in 25.64 per cent of patients. After antimalarial treatment
      with chloroquine and primaquine and supportive care all patients were
      successfully discharged. No deaths or further complications were seen, except for
      persistent mild thrombocytopenia in 17.95 per cent of the patients.

PMID- 15980020
TI  - The evaluation and cluster analysis of parapneumonic effusion in childhood.
AB  - We studied 80 children with parapneumonic effusion (PPE) with respect to the
      clinical manifestations and treatment alternatives as well as prospective follow
      up for 1 year. Out of the 80 patients, 59 per cent were male. The mean age of the
      patients was 4.0 +/- 3.1 years. Mild effusion was successfully treated by
      antibiotic alone in 33 per cent of the patients. Tube thoracostomy (TT) was
      utilized in 63 per cent of the patients. In this group, 11 healed completely, 13
      patients required surgical treatment, and 25 required fibrinolytic therapy (FT).
      FT was successful in 18, and no complication due to FT was observed. Six patients
      who received FT required surgical therapy later in the course of treatment.
      Cluster analysis revealed a group of patients with rapid progression and a short
      history of symptoms (4-6 days) that showed significantly higher rate of
      complicated prognosis (p<0.05). Successful FT prevented surgical operation in 22
      per cent of the patients who were candidates for surgical treatment. The follow
      up for one year revealed sequelae on chest X-ray in 28 per cent of the patients
      most of whom had an operation for necrotizing pneumonia. Pulmonary function tests
      performed over seven years of age were abnormal in 57 per cent of the patients.

PMID- 15980021
TI  - Henoch-Schonlein purpura in a child following varicella.
AB  - Henoch-Schonlein purpura (HSP) is one of the most common vasculitis of childhood.
      It is characterized by nonthrombocytopenic palpable purpura, arthritis, renal and
      gastrointestinal system (GIS) involvement. HSP is usually triggered by an
      antigenic stimulus including infectious agents, drugs, cold, insect bite or food.
      HSP is rarely triggered by Varicella zoster infection. We herein presented a case
      with HSP following varicella.

PMID- 15980023
TI  - Study of substance P, renin and aldosterone in chronic liver disease in Egyptian
      children.
AB  - Substance P is the most powerful endogenous vasodilator peptide produced by the
      enteric nervous system and partly cleared by the liver. Failure of the diseased
      liver to metabolize a vasodilator substance may be responsible for the rebound
      increased plasma level of vasoconstrictor intestinal peptide. AIM: To investigate
      the plasma level of Substance P and to study its relationship to aldosterone and
      plasma renin activity changes occurring in pediatric patients with chronic liver
      disease. METHODS: Forty patients with chronic liver disease and 10 healthy
      children were tested for AST, ALT, total and direct bilirubin, creatinine,
      aldosterone, plasma renin activity and plasma level of Substance P. RESULTS: The
      plasma level of Substance P was increased in all patients with chronic liver
      disease (119.5+/-68.2 pg/ml) compared to controls (16.2+/-4.6 pg/ml). The
      aldosterone concentration and plasma renin activity were significantly higher in
      patients [(84.1+/-38.3 ng/dl) and (11.1+/-7.3 ng/ml/h)] than controls [(8.2+/-3.9
      ng/dl) and (2.0+/-1.1 ng/ml/h)]. The highest level of Substance P and aldosterone
      were observed in glycogen storage disease patients. CONCLUSION: Substance P was
      found to be increased in chronic liver disease patients; this increase was
      accompanied by an increase of aldosterone and plasma rennin activity. This
      correlation raises its potential use as a prognostic marker in chronic liver
      diseases.

PMID- 15980024
TI  - Maternal anthropometry as predictors of low birth weight.
AB  - The usefulness of maternal anthropometric parameters i.e. maternal weight (MWt),
      maternal height (MHt), maternal mid-arm circumference (MMAC) and maternal body
      mass index (MBMI) as predictors of low birth weight (LBW) was studied in 395
      singleton pregnancies. The maternal anthropometric parameters were measured in
      the first trimester of pregnancy and were plotted against the birth weight of the
      newborns. Significant positive correlations were observed among MWt and birth
      weight (r=0.38), MHt and birth weight (r=0.25), MMAC and birth weight (r=0.30)
      and MBMI and birth weight (r=0.30). The most sensitive being MWt (t=7.796),
      followed by MMAC (t=5.759), MHt (t=4.706) and MBMI (t=5.89). For prediction of
      LBW, the critical limits of MWt, MHt, MMAC and MBMI were 45 kg, 152 cm, 22.5 cm,
      20 kg/m2 respectively. From these observations, the use of colour-coded weighing
      machines, height rods and tapes may be devised for use by peripheral health
      workers and traditional birth attendants for detection of mothers at risk of
      delivering low birth weight babies (Table 5). Mothers who have anthropometric
      parameters in the 'red zone' are at risk of delivery LBW infants.

PMID- 15980025
TI  - Adverse drug reactions in a department of pediatric surgery.

PMID- 15980026
TI  - Antibiotic treatment of community acquired pneumonia in well-nourished young
      Nigerian children.

PMID- 15980027
TI  - Age related clinical manifestations of HIV infection in Indian children.
AB  - AIM: To determine the various clinical manifestations of HIV infection in
      children as per the age. SETTING: Pediatric and Perinatal HIV clinic in a
      tertiary pediatric hospital over a period of 7 years. STUDY DESIGN: Retrospective
      and prospective analysis. METHODS AND MATERIALS: Clinical manifestations of 317
      HIV infected children were noted and commonest clinical symptoms were determined.
      The various clinical manifestations as per age were analysed. RESULTS: The mean
      age of presentation of HIV infection was 4.5+/-2.9 years. Predominant mode of
      transmission was vertical (83 per cent). Most of the children (75 per cent) were
      in Class B or C on presentation. There was no significant difference in the
      clinical symptoms and mode of transmission of HIV. The predominant clinical
      features seen were hepato-splenomegaly (51.1 per cent), lymphadenopathy (48.6 per
      cent) and tuberculosis (43.4 per cent). Patients with vertical transmission
      presented at an early mean age of 4.1+/-2.7 years as compared to those who
      acquired it by other means, which was statistically significant. PCP pneumonia
      was the earliest manifestation in toddlers and hepatosplenomegaly,
      lymphadenopathy, chronic diarrhea was seen in pre-schoolers. Systemic organ
      dysfunction due to HIV was seen in older children. CONCLUSIONS:
      Hepatosplenomegaly, lymphadenopathy and opportunistic infections together in a
      child may be suggestive of HIV infection. High suspicion and early diagnosis will
      lead to early management and decrease in the incidence of HIV related morbidity.

PMID- 15980028
TI  - Plasmodium falciparum malaria in Nigerian children during high and low
      transmission seasons: gametocyte carriage and response to oral chloroquine.
AB  - Plasmodium falciparum malaria during high and low transmission seasons was
      evaluated in 1031 children treated with different antimalarial drug in a
      hyperendemic area of southwestern Nigeria. Seventy-three (10.5%) of 693 and forty
      (11.8%) of 338 children were gametocyte carriers in the high transmission seasons
      (HTS) and low transmission seasons (LTS), respectively. In a multiple regression
      model, two factors were found to be independent risk factors for the presence of
      gametocytemia at enrolment in the HTS: duration of illness >3 d, and asexual
      parasite densities less than 10,000/microl. Similarly male gender, duration of
      illness >4 d and parasite density less than 5000/mul were found independent risk
      factors for presence of gametocytemia during LTS. The presenting parasitemia,
      parasite clearance times, intensity of gametocytemia and proportion carrying
      gametocytes post treatment differ significantly in the 333 (32.3%) of these
      children that were treated with chloroquine in the two seasons. These findings
      may be important in our understanding of P. falciparum transmission sustenance,
      response to chloroquine therapy and contribution of chloroquine to gametocyte
      carriage as seasonal changes occur.

PMID- 15980029
TI  - Mycoplasma pneumoniae infection in children with acute respiratory infection.
AB  - A prospective study was performed on 93 children admitted to Kasturba Medical
      College Hospital, Manipal and TMA Pai Rotary Hospital of Udupi and Karkala. Blood
      samples from 93 children admitted to the ward with no respiratory illness were
      taken as age-matched controls for the inpatients, IgM antibody against Mycoplasma
      pneumoniae was detected using a commercial kit (Virion-Serion ELISA, Germany)
      following the manufacturer's instructions. 23.96% of the inpatients with
      respiratory tract symptoms had IgM antibodies against Mycoplasma pneumoniae. The
      highest infection rate was found to be in the 2-5 and 5-10 year age group. The
      most common mode of presentation was an upper respiratory focus of infection with
      cervical lymphadenopathy. Bronchial breathing signifying pneumonic consolidation
      was significantly less in the Mycoplasma positive group (p = 0.006). There was no
      statistically significant difference in the radiological findings in the
      Mycoplasma positive and Mycoplasma negative groups.

PMID- 15980030
TI  - Prevalence of congenital malaria in Ile-ife, Nigeria.
AB  - The study was designed to determine the prevalence of congenital malaria, cord
      blood and placental malaria parasitaemia and the prevalence of clinical
      manifestations of congenital malaria. Ile-Ife is a holoendemic area for malaria.
      Placental, cord and peripheral blood smears of 120 newborn babies were examined
      for malaria parasites. They consisted of 104 (86.7 per cent) full term babies and
      16 (13.3 per cent) preterm babies. Positive parasitaemia was found in 56 (46.7
      per cent) of peripheral blood smears, 68 (56.7 per cent) and 65 (54.2 per cent)
      of the placental and cord blood smears respectively. There were strong
      associations between placental malaria and cord malaria parasitaemia and
      congenital malaria (p < 0.001). Congenital malaria has a high prevalence in Ile
      Ife. There is a paucity of its clinical manifestations in the newborn. Only two
      babies had fever within 48 hours of birth.

PMID- 15980031
TI  - Vitamin A deficiency and child mortality in Cameroon: the challenge ahead.

PMID- 15980032
TI  - The importance of the gastrointestinal system in the pathogenesis of heart
      failure.
AB  - Chronic heart failure (CHF) is a multi-organ disease with increasing evidence for
      the involvement of the gastrointestinal (GI) system in this syndrome. In recent
      research, the gut has received very little attention from cardiologists as its
      role in the pathogenesis of cardiovascular disease is poorly understood.
      Intestinal ischaemia may play an important role in bacterial translocation by
      increasing bowel permeability. Decreased cardiac function can reduce bowel
      perfusion and so clearly impairs the function of the intestinal barrier. There is
      an increasing evidence to suggest that a 'leaky' bowel wall may lead to
      translocation of bacteria and/or endotoxin, which may be an important stimulus
      for inflammatory cytokine activation in CHF. Impaired functioning of the GI
      system may also contribute to malnutrition and cachexia in CHF. It is hoped that
      by improving our understanding of the role of the gut in cardiac disease will
      lead to the development of novel therapeutic strategies in the future.

PMID- 15980033
TI  - Familial recurrence of congenital heart disease in patients with ostium secundum
      atrial septal defect.
AB  - AIMS: Ostium secundum atrial septal defect (osASD) is one of the most common
      cardiac malformations. Few data are available on the familial recurrence of
      congenital heart disease (CHD), in particular, in a large group of patients with
      isolated osASD. The aim is to investigate the familial recurrence of CHD in up to
      third-degree relatives from a large sample of consecutively enrolled patients
      with osASD, taking into account the influence of degree of relatedness (as number
      of relatives). METHODS AND RESULTS: From January 1998 to December 2002, we
      enrolled 583 patients with osASD and 408 healthy subjects, referred to our
      tertiary centre. We hypothesized that a positive family history required at least
      one relative with CHD to constitute a risk factor. In this model of analysis, the
      null hypothesis is a similar familial history between cases and controls. Among
      583 patients with osASD, 109 (19%) had at least one relative with CHD. Among the
      408 healthy subjects studied, only 23 (6%) had a family history of CHD. A
      familial recurrence of CHD was demonstrated in 72 of 312 (23%) patients with
      isolated osASD and in 37 of 271 (13.6%) patients with non-isolated osASD.
      Familial recurrence of isolated osASD was demonstrated in 22 of 312 patients (7%)
      with an isolated osASD and only in six of 271 patients (2.2%) with non-isolated
      osASD. The familial recurrence risk of isolated osASD in patients with isolated
      osASD was higher in sibs, especially in sisters (33.3%). CONCLUSION: This study
      underscores the role of genetic factors in the determination of CHD, particularly
      osASD. Our results could represent the basis for further studies to calculate a
      'value of family history' to adapt the familial recurrence to the real size of
      each family group. In this way, we could select families with a 'tendency' to
      develop CHD, particularly osASD. In these families, we could analyse the genetic
      pattern to establish abnormalities and the bases of CHD.

PMID- 15980034
TI  - Diabetes, glucose level, and risk of sudden cardiac death.
AB  - AIMS: The prevalence of diabetes mellitus in industrialized countries is rapidly
      increasing, and diabetes is suspected to carry a particular high risk for sudden
      cardiac death (SCD). METHODS AND RESULTS: We conducted a population-based case
      control study at Group Health Cooperative. Cases (n=2040) experienced out-of
      hospital cardiac arrest due to heart disease between 1980 and 1994. Controls
      (n=3800) were a stratified random sample of enrollees. Diabetes status was
      classified into four exclusive groups: (i) no diabetes, (ii) borderline, (iii)
      diabetes without microvascular disease (retinopathy or proteinuria), and (iv)
      diabetes with microvascular disease. When compared with no diabetes, we observed
      progressively higher risk of SCD associated with borderline diabetes [Odds ratio
      (OR)=1.24 (0.98-1.57)], diabetes without microvascular disease [OR=1.73 (1.28
      2.34)], and diabetes with microvascular disease [OR=2.66 (1.84-3.85)], after
      adjustment for potential confounders (P-value for trend <0.001). Higher glucose
      levels were also associated with the risk of SCD both in the absence and in the
      presence of microvascular disease. However, subjects with microvascular
      complications but with glucose level <7.7 mmol/L were not at significant
      increased risk of SCD. CONCLUSION: These results emphasize the role of diabetes
      as a strong risk factor for SCD and outline the importance of glucose level at
      every stage of diabetes severity.

PMID- 15980035
TI  - p38 and EGF receptor kinase-mediated activation of the phosphatidylinositol 3
      kinase/Akt pathway is required for Zn2+-induced cyclooxygenase-2 expression.
AB  - Cyclooxygenase 2 (COX-2) expression is induced by physiological and inflammatory
      stimuli. Regulation of COX-2 expression is stimulus and cell type specific.
      Exposure to Zn2+ has been associated with activation of multiple intracellular
      signaling pathways as well as the induction of COX-2 expression. This study aims
      to elucidate the role of intracellular signaling pathways in Zn2+-induced COX-2
      expression in human bronchial epithelial cells. Inhibitors of the
      phosphatidylinositol 3-kinase (PI3K) potently block Zn2+-induced COX-2 mRNA and
      protein expression. Overexpression of adenoviral constructs encoding dominant
      negative Akt kinase downstream of PI3K or wild-type phosphatase and tensin
      homolog deleted on chromosome 10, an important PI3K phosphatase, suppresses COX-2
      mRNA expression induced by Zn2+. Zn2+ exposure induces phosphorylation of the
      tyrosine kinases, including Src and EGF receptor (EGFR), and the p38 mitogen
      activated protein kinase. Blockage of these kinases results in inhibition of Zn2+
      induced Akt phosphorylation as well as COX-2 protein expression. Overexpression
      of dominant negative p38 constructs suppresses Zn2+-induced increase in COX-2
      promoter activity. In contrast, the c-Jun NH2-terminal kinase and the
      extracellular signal-regulated kinases have minimal effect on Akt phosphorylation
      and COX-2 expression. Inhibition of p38, Src, and EGFR kinases with
      pharmacological inhibitors markedly reduces Akt phosphorylation induced by Zn2+.
      However, the PI3K inhibitors do not show inhibitory effects on p38, Src, and
      EGFR. These data suggest that p38 and EGFR kinase-mediated Akt activation is
      required for Zn2+-induced COX-2 expression and that the PI3K/Akt signaling
      pathway plays a central role in this event.

PMID- 15980036
TI  - Molecular imaging of lung glucose uptake after endotoxin in mice.
AB  - Positron emission tomographic imaging after administration of the glucose analog
      fluorine-18 fluorodeoxyglucose ([18F]FDG) may be useful to study neutrophilic
      inflammation of the lungs. In this study, we sought to determine the specificity
      of the increase in lung [18F]FDG uptake after intraperitoneal endotoxin (Etx) for
      neutrophil influx into mouse lungs and to determine the regulation of glucose
      uptake after Etx by Toll-like receptors (TLRs) and TNF-alpha. Lung tissue
      radioactivity measurements by imaging were validated against counts in a gamma
      well counter. Glucose uptake was quantified as the [18F]FDG tissue-to-blood
      radioactivity ratio (TBR) after validating this measure against the "gold
      standard" measure of glucose uptake, the "net influx rate constant." TBR
      measurements were made in a control group (no intervention), a group administered
      Etx, and a group administered Etx plus an additional agent (e.g., vinblastine) or
      Etx administered to a mutant mouse strain. The glucose uptake measurements were
      compared with measurements of myeloperoxidase. Increases in TBR after Etx were
      significantly but not completely eliminated by neutrophil depletion with
      vinblastine. Increases in TBR after Etx were consistent with signaling via either
      TLR-4 or TLR-2 (the latter probably secondary to peptidoglycan contaminants in
      Etx preparation) and were decreased by drug inhibition of TLR-4 but not by
      inhibition of TNF-alpha. Thus molecular imaging can be used to noninvasively
      monitor biological effects of Etx on lungs in mice, and changes in lung glucose
      uptake can be used to monitor effects of anti-inflammatory agents. Such imaging
      capacity provides a powerful new paradigm for translational "mouse-to-human"
      pulmonary research.

PMID- 15980037
TI  - Surfactant protein D decreases pollen-induced IgE-dependent mast cell
      degranulation.
AB  - Mast cells play a key role in allergy and asthma. They reside at the host
      environment interface and are among the first cells to make contact with inhaled
      microorganisms and particulate antigens. Pulmonary surfactant proteins A and D
      (SP-A and SP-D) function in lung host defense by enhancing microbe phagocytosis
      and mediating other immune cell functions, but little is known about their
      effects on mast cells. We hypothesized that SP-A and/or SP-D modulate IgE
      dependent mast cell functions. Pollen starch granules (PSG) extracted from
      Dactylis glomerata and coated with trinitrophenol (TNP) were used as a model of
      an inhaled organic particulate allergen. Our data revealed that SP-D inhibited by
      50% the release of beta-hexosaminidase by peritoneal mast cells sensitized with
      IgE anti-TNP and stimulated with TNP-PSG. In contrast, SP-A had no effect.
      Furthermore, SP-D aggregated PSG in a dose-dependent manner, and this aggregation
      was mediated by SP-D's carbohydrate recognition domain. A single arm SP-D mutant
      (RrSP-Dser15,20) neither aggregated PSG nor inhibited degranulation, suggesting
      that multimerization of SP-D is required for maximal PSG aggregation and
      inhibition of PSG-induced mast cell degranulation. This study is the first to
      demonstrate that SP-D modulates IgE-mediated mast cell functions, which are
      important in asthma and allergic inflammation.

PMID- 15980038
TI  - Fas-associated death-domain protein inhibits TNF-alpha mediated NF-kappaB
      activation in cardiomyocytes.
AB  - Fas-associated death-domain protein (FADD) is an adaptor molecule that links
      death receptors to caspase-8 in many cell types including cardiomyocytes (CMs).
      Although FADD has previously been reported to play an important role in CM
      apoptosis, the effect of FADD on CM NF-kappaB signaling, which is a
      proinflammatory pathway, has not been delineated. To investigate the role of FADD
      in CM NF-kappaB activation, we utilized adenoviral gene transfer of wild-type
      FADD and a truncation mutant that lacks the death-effector domain (FADD-DED) in
      rat CMs in vitro TNF-alpha activated NF-kappaB in CMs as demonstrated by
      phosphorylation and degradation of inhibitory-kappaB (IkappaB)-alpha-enhanced
      nuclear p65 and NF-kappaB DNA-binding activity as well as increased mRNA for the
      NF-kappaB-dependent adhesion molecule VCAM-1 (19 +/- 4.1-fold) as measured by
      quantitative RT-PCR. Gene transfer of FADD inhibited TNF-alpha-induced IkappaB
      alpha phosphorylation, decreased p65 nuclear translocation and NF-kappaB DNA
      binding activity, and reduced VCAM-1 transcript levels by 53-65%. Interestingly,
      FADD-DED exhibited a similar but weaker inhibitory effect on NF-kappaB
      activation. The effects of FADD on NF-kappaB were cell-type specific. FADD
      expression also inhibited TNF-alpha-mediated NF-kappaB activation in human
      endothelial cells but not in rat pulmonary artery smooth muscle cells. In
      contrast, FADD expression actually activated NF-kappaB in human embryonic kidney
      (HEK)-293 cells. In CMs, FADD inhibited NF-kappaB activation as well as
      phosphorylation of IkappaB-alpha and IkappaB kinase (IKK)-beta in response to
      cytokine stimulation or expression of the upstream kinases NF-kappaB-inducing
      kinase and IKK-beta. These data demonstrate that FADD inhibits NF-kappaB
      activation in CMs, and this inhibition likely occurs at the level of
      phosphorylation and activation of IKK-beta.

PMID- 15980039
TI  - Relative contribution of Rho kinase and protein kinase C to myogenic tone in rat
      cerebral arteries in hypertension.
AB  - Arterial smooth muscle constriction in response to pressure, i.e., myogenic tone,
      may involve calcium-dependent and calcium-sensitization mechanisms. Calcium
      sensitization in vascular smooth muscle is regulated by kinases such as PKC and
      Rho kinase, and activity of these kinases is known to be altered in
      cardiovascular disorders. In the present study, we evaluated the relative
      contribution of PKC and Rho kinase to myogenic tone in cerebral arteries in
      hypertension. Myogenic tone and arterial wall calcium in Wistar-Kyoto (WKY) rats
      and spontaneously hypertensive rats (SHR) were measured simultaneously, and the
      effect of PKC and Rho kinase inhibitors on myogenic tone was evaluated. SHR
      arteries showed significantly greater myogenic tone than WKY arteries.
      Pressure/wall tension-arterial wall calcium curves showed a hyperbolic relation
      in WKY rats, but the curves for SHR arteries were parabolic. Myogenic tone was
      decreased by the Rho kinase inhibitors Y-27632 and HA-1077, with a significantly
      greater effect in SHR than in WKY arteries. Reduction in myogenic tone produced
      by the PKC inhibitor bisindolylmaleimide I in WKY and SHR arteries was
      significantly less than that produced by Rho kinase inhibition. The pressure
      dependent increase in myogenic tone was significantly decreased by Y-27632, and
      the decrease was markedly greater than that produced by bisindolylmaleimide I in
      SHR arteries. In WKY arteries, the pressure-dependent increase in myogenic tone
      was decreased to a similar extent by Y-27632 and bisindolylmaleimide I. These
      results suggest greater myogenic tone with increased calcium sensitization in SHR
      arteries, largely because of Rho kinase activation, with a minor contribution of
      PKC activation.

PMID- 15980040
TI  - Inhibitor-kappaB kinase-beta regulates LPS-induced TNF-alpha production in
      cardiac myocytes through modulation of NF-kappaB p65 subunit phosphorylation.
AB  - TNF-alpha is recognized as a significant contributor to myocardial dysfunction.
      Although several studies suggest that members of the NF-kappaB family of
      transcription factors are essential regulators of myocardial TNF-alpha gene
      expression, recent developments in our understanding of the modulation of NF
      kappaB activity through posttranslational modification of NF-kappaB subunits
      suggest that the present view of NF-kappaB-dependent cytokine expression in heart
      is incomplete. Therefore, the goal of the present study was to examine the role
      of p65 subunit phosphorylation in the regulation of TNF-alpha production in
      cultured neonatal ventricular myocytes. Bacterial LPS-induced TNF-alpha
      production is accompanied by a 12-fold increase in phosphorylation of p65 at
      Ser536, a modification associated with enhancement of p65 transactivation
      potential. Pharmacological inhibition of IKK-beta reduced LPS-induced TNF-alpha
      production 38-fold, TNF-alpha mRNA levels 6-fold, and IkappaB-alpha
      phosphorylation 5-fold and degraded IkappaB-alpha 2-fold and p65 phosphorylation
      6-fold. Overexpression of dominant-negative p65 reduced TNF-alpha production 3.5
      fold, whereas overexpression of dominant-negative IKK-beta reduced LPS-induced
      TNF-alpha production 2-fold and p65 phosphorylation 2-fold. Overexpression of
      dominant-negative IKK-alpha had no effect on p65 phosphorylation or TNF-alpha
      production, revealing that IKK-beta, not IKK-alpha, plays a central role in
      regulation of p65 phosphorylation at Ser536 and TNF-alpha production in heart.
      Finally, we demonstrated, using a chromatin immunoprecipitation assay, that LPS
      stimulates recruitment of Ser536-phosphorylated p65 to the TNF-alpha gene
      promoter in cardiac myocytes. Taken together, these data provide compelling
      evidence for the role of NF-kappaB signaling in TNF-alpha gene expression in
      heart and highlight the importance of this proinflammatory gene-regulatory
      pathway as a potential therapeutic target in the management of cytokine-induced
      myocardial dysfunction.

PMID- 15980041
TI  - Prevention of latex sensitization in guinea pigs by a bacterial and viral filter
      used in anaesthesia.
AB  - BACKGROUND: Preventing anaphylactic reactions as a result of natural rubber latex
      (NRL) proteins is an important concern in anaesthesia. The clinical relevance of
      a bacterial/viral filter (Pall BB25) in preventing sensitization to NRL by
      inhalation was tested in guinea pigs. METHODS: Guinea pigs (n=8-10 in each group)
      were exposed to aerosolized NRL-contaminated cornstarch powder or to NRL in
      saline for 1 h every day for 2 weeks. The experiments were repeated with a Pall
      BB25 filter placed over the aerosol system. Control groups were exposed to non
      contaminated cornstarch or to saline alone. Three weeks after the last exposure,
      specific bronchial challenge was performed and thromboxane (Tx) B2 levels in
      bronchoalveolar lavage fluid were measured. RESULTS: After bronchial challenge,
      the animals exposed to NRL or NRL-contaminated cornstarch with the BB25 filter in
      place showed a level of bronchoconstriction (i.e. the variation of pulmonary
      insufflation pressure) not different from controls. Conversely, those exposed to
      NRL or NRL-contaminated cornstarch without the filter showed a higher level of
      bronchoconstriction (respectively, P<0.02 and P<0.001) than control. Elevated
      TxB2 levels were found in the lungs of the guinea pigs, which inhaled NRL or NRL
      contaminated cornstarch in the absence of a filter. Animals treated with the
      filter showed comparable TxB2 levels with those of control. CONCLUSION: The Pall
      BB25 filter efficiently protected the guinea pigs from sensitization to NRL. This
      filter can be used as a complementary measure for avoidance of NRL contact during
      surgical procedures particularly if the mechanical ventilator apparatus contain
      NRL devices.

PMID- 15980042
TI  - The effects of halothane and isoflurane on cardiovascular function in laterally
      recumbent horses.
AB  - BACKGROUND: Experimental studies in adult horses have shown that general
      anaesthesia maintained with isoflurane is associated with less depression of
      cardiovascular function compared with halothane anaesthesia. Adverse effects of
      intermittent positive-pressure ventilation (IPPV) have also been demonstrated.
      Nevertheless, the haemodynamic effects of these agents and the effects of
      differing modes of ventilation have not been assessed during clinical anaesthesia
      in horses undergoing surgery. METHODS: The haemodynamic effects of isoflurane or
      halothane anaesthesia during spontaneous or IPPV were studied non-invasively in
      32 laterally recumbent horses undergoing elective surgery. Indices of cardiac
      function and measurements of femoral arterial blood flow and resistance were
      recorded using transoesophageal and transcutaneous Doppler echocardiography,
      respectively. Arterial pressure was measured directly using a facial artery
      catheter. RESULTS: Cardiac index (CI) was significantly higher during isoflurane
      anaesthesia than during halothane anaesthesia and was also higher during
      spontaneous ventilation with isoflurane. CI decreased significantly over time and
      an inverse relationship was observed between CI and mean arterial pressure (MAP).
      Horses with higher MAP had a significantly lower CI. During isoflurane
      anaesthesia, femoral arterial blood flow was significantly higher in both pelvic
      limbs compared with halothane anaesthesia, and flow in the lower limb was
      significantly higher during spontaneous ventilation than during IPPV. No
      significant change in femoral blood flow was observed over time. CONCLUSION: The
      effects of anaesthetics and mode of ventilation on cardiovascular function
      recorded under surgical conditions in horses are similar to those reported under
      experimental conditions. However, in contrast with previous experimental studies,
      CI progressively decreased over time regardless of agent used or mode of
      ventilation employed.

PMID- 15980043
TI  - Development of acute tolerance to the EEG effect of propofol in rats.
AB  - BACKGROUND: A previous study in rats with propofol suggested the development of
      acute tolerance to the EEG effect. The aim of this study was to evaluate acute
      tolerance by means of EEG-controlled closed-loop anaesthesia as this approach
      allows precise determination of drug requirement to maintain a defined drug
      effect. METHODS: Ten male Sprague-Dawley rats [weight 402 (40) g, mean (SD)] were
      included in the study. The EEG was recorded with occipito-occipital needle
      electrodes and a modified median frequency (mMEF) of the EEG power spectrum was
      used as a pharmacodynamic control parameter. The propofol infusion rate was
      controlled by a model-based adaptive algorithm to maintain a set point of mMEF=3
      (0.5) Hz for 90 min. The performance of the closed-loop system was characterized
      by the prediction error PE=(mMEF-set point)/set point. Plasma propofol
      concentrations were determined from arterial samples by HPLC. RESULTS: The chosen
      set point was successfully maintained in all rats. The median (SE) and absolute
      median values of PE were -5.0 (0.3) and 11.3 (0.2)% respectively. Propofol
      concentration increased significantly from 2.9 (2.2) microg ml(-1) at the
      beginning to 5.8 (3.8) microg ml(-1) at 90 min [mean (SD), P<0.05]. The
      cumulative dose increased linearly, with a mean infusion rate of 0.60 (0.16) mg
      kg(-1) min(-1). The minimum value of the mean arterial pressure during closed
      loop administration of propofol was 130 (24) mm Hg, compared with a baseline
      value of 141 (12) mm Hg. CONCLUSIONS: The increase in propofol concentration at
      constant EEG effect indicates development of acute tolerance to the hypnotic
      effect of propofol.

PMID- 15980044
TI  - Effects of PEEP on oxygenation and respiratory mechanics during one-lung
      ventilation.
AB  - BACKGROUND: One-lung ventilation-related hypoxaemia (OLV-RH) can occur in
      patients with healthy lungs. In this case, PEEP frequently improves oxygenation.
      The aim of this study was to determine, in a healthy lung model of OLV, whether
      the increase in PEEP improved oxygenation and whether the mechanisms involved
      include both inspiratory lung recruitment and an end-expiratory lung volume
      increase. Since inhaled nitric oxide (iNO) may have a synergistic effect on
      oxygenation in the case of PEEP-induced recruitment, their association was also
      tested. METHODS: Twenty pigs were studied during open-chest, left OLV. Arterial
      blood gases and haemodynamic variables were measured at different levels of PEEP
      (0, 5, 10 and 15 cm H(2)O) applied in random order with or without iNO 4 p.p.m.
      Pressure-volume curves were measured at each level of PEEP. RESULTS: PEEP(5) and
      PEEP(10) improved Pa(O(2))/FI(O(2)) ratio (P<0.005) and shunt (P<0.005)
      regardless of the presence of iNO. PEEP(15) improved oxygenation and shunt only
      when it was associated with iNO (P<0.001). Whereas PEEP(5), PEEP(10) and PEEP(15)
      were associated with a significant increase in end-expiratory volume (P<0.001),
      only PEEP(5) and PEEP(10) were associated with continuous lung volume recruitment
      (P<0.01). Moreover, PEEP(15) induced a significant decrease in linear compliance
      (P<0.001). CONCLUSIONS: In a healthy porcine lung model of OLV-RH, moderate PEEP
      can improve oxygenation. This effect implies both expiratory and inspiratory
      pulmonary recruitment. Co-administration of 4 p.p.m. iNO was ineffective.

PMID- 15980045
TI  - The dependence of measured alveolar deadspace on anatomical deadspace volume.
AB  - BACKGROUND: Changes in pulmonary deadspace are indicators of disease status (e.g.
      pulmonary embolus, acute respiratory distress syndrome) and they have prognostic
      usefulness in the intensive care unit. The components of pulmonary deadspace, the
      alveolar and anatomical deadspaces (VDalv and VDanat), are commonly considered to
      be independent (i.e. the addition of airway equipment should not alter the
      measured VDalv). However, VDanat has been shown to affect VDalv in the absence of
      changes in alveolar ventilation or perfusion. We sought to quantify the
      variability in measured VDalv induced by changes in VDanat using a
      cardiorespiratory computational model. METHODS: Using the Nottingham Physiology
      Simulator, we examined three simulated ventilated patients with small, moderate
      and large ventilation-perfusion (VQ) defects. Each patient received 12.5 bpm x
      500 ml. We varied VDanat between 50 and 250 ml, keeping the VQ ratio of each
      alveolus constant. We calculated VDalv by subtracting VDanat (measured using
      Fowler's technique) from the physiological deadspace (measured using the Bohr
      Enghoff equation). We calculated fresh-gas tidal volume (VTfresh) by subtracting
      VDanat from the exhaled tidal volume and calculated VDalv/VTfresh. In the
      simulated patient with the large VQ defect, we performed the same protocol with
      tidal volumes of 750 and 1000 ml. RESULTS: When VDanat increased from 50 to 250
      ml (500 ml tidal volume) VDalv decreased by 48.3% (mean value across the three VQ
      defects) and VDalv/VTfresh decreased by 15.1%. These relationships were similar
      at each tidal volume studied. CONCLUSIONS: Measured VDalv is altered by changes
      in VDanat despite constant VQ ratios in each alveolus. This has implications for
      the interpretation of deadspace measured in the clinical setting. The variability
      is less for the ratio VDalv/VTfresh.

PMID- 15980046
TI  - Concurrent recording of AEP, SSEP and EEG parameters during anaesthesia: a factor
      analysis.
AB  - BACKGROUND: Spontaneous EEG, mid-latency auditory evoked potentials (AEP) and
      somatosensory evoked potentials (SSEP) have been used to monitor anaesthesia.
      This poses the question as to whether or not EEG, AEP and SSEP vary in parallel
      with varying conditions during surgical anaesthesia. METHODS: A total of 81
      variables (31 EEG, 22 SSEP, 28 AEP) were simultaneously recorded in 48 surgical
      patients during anaesthesia. A total of 307 cases of the 81 variables in stable
      anaesthetic states were recorded. A factor analysis was performed for this data
      set. RESULTS: Sixteen variables were excluded because of multicollinearity. We
      extracted 13 factors with eigenvalues >1, representing 78.3% of the total
      variance, from the remaining 65 x 307 matrix. The first three factors represented
      12%, 11% and 10% of the total variance. Factor 1 had only significant loadings
      from EEG variables, factor 2 only significant loadings from AEP variables and
      factor 3 only significant loadings from SSEP variables. CONCLUSION: EEG, AEP and
      SSEP measure different aspects of neural processing during anaesthesia. This
      gives rise to the hypothesis that simultaneous monitoring of these quantities may
      give additional information compared with the monitoring of each quantity alone.

PMID- 15980047
TI  - Culturally competent scholarship in nursing research.
AB  - PURPOSE: To determine the degree to which research reports published in major
      nursing research journals reflected Meleis's eight criteria for culturally
      competent scholarship. DESIGN: Analytic review of 167 studies dealing with race,
      ethnicity, or culture from four nursing research journals, 1992-2000. METHOD:
      Four reviewers selected, abstracted, and scored research articles independently,
      in pairs, and as a group. FINDINGS: The mean and median Meleis scores were 2.92
      and 3.00 on an 8-point scale. All scores were assigned at least once.
      Contextuality, relevance, and communication style were most frequently present;
      disclosure, empowerment, and time were least frequently present. IMPLICATIONS:
      Assignment of Meleis scores is feasible and useful for evaluating cultural
      competence of research reports.

PMID- 15980048
TI  - Disclosing concerns of Latinas living with HIV/AIDS.
AB  - This study described the disclosing experiences of Latinas with HIV/AIDS in the
      San Francisco Bay Area. Limited information is available on the disclosing
      processes, situations and consequences. The design was a descriptive study with
      19 Latinas. Content analysis was used to analyze the data. Deciding to disclose
      was identified as the core category. Four major categories emerged from the data.
      Deciding to disclose has social, psychological and economical issues. Nurses need
      to be aware of the disclosing issues when caring for Latinas with HIV/AIDS.

PMID- 15980049
TI  - Tenerlos en la Casa: the material world and craft of family caregiving for
      relatives with dementia.
AB  - The environment has been found to be critical to the well-being of patients with
      dementia. The purpose of this study was to describe strategies Colombian
      caregivers used in the home to manage the care of relatives with dementia.
      Grounded theory techniques were used. Interviews were conducted in Medellin,
      Colombia, with 18 primary caregivers and 2 health care professionals. Participant
      observations were conducted in caregivers' support groups and homes. Family
      caregivers rebuilt the environment as the disease progressed to accommodate
      caregiving and preserve family life. Caring for a relative with dementia is a
      craft that transforms the material world in which patient and caregiver live. The
      findings show the value of place-sensitive approaches to the study and practice
      of caregiving.

PMID- 15980050
TI  - The nutritional patterns of recently immigrated Honduran women.
AB  - This descriptive, exploratory study on nutritional patterns of newly immigrated
      Honduran women allows a better understanding of health-related nutrition issues
      in this Hispanic subgroup. Five focus group discussions were conducted in Spanish
      with 23 Honduran women, ages 25 to 60 years, living in New Orleans, who had
      immigrated to the United States within the past 10 years. Positive health-related
      changes included an increase in fruit and vegetable intake, food preparation
      using less grease, and baking rather than frying. Negative changes included
      skipping meals and eating high-fat fast foods. The Hondurans' traditional diet
      and positive dietary changes should be supported.

PMID- 15980051
TI  - An ethnonursing research study: adults residing in a midwestern Christian
      philosophy urban homeless shelter.
AB  - The ethnonursing study's purpose was to explore the subculture of homeless adults
      residing in one shelter, with discovery of their meanings and experiences of
      care, or lack of care. Leininger's theory of culture care was used to identify,
      analyze, and discuss the cultural care patterns. The findings included themes
      that were identified in two categories: two themes before shelter residence (no
      caring practices in their lives) and two themes during shelter residence
      (acceptance and hope). Ethnonursing discovery contributes to nurses' knowledge
      about who the homeless people are and why they are homeless and develops
      culturally congruent care practices.

PMID- 15980052
TI  - Perceptions of lung cancer and smoking among college students in Jordan.
AB  - A descriptive, cross-sectional design was adopted to identify college students'
      knowledge and perceptions of lung cancer and smoking. A random sample of 400
      students at the Jordan University of Science and Technology in northern Jordan
      was subjected to the Lung Cancer and Smoking Survey, which is based on the Health
      Belief Model. The results show that the prevalence of current smoking is 16.5%
      and that the prevalence of former smoking is 10.0%. Most (75.3%) of the
      respondents were aware of the prevalence of lung cancer. Almost all (90.3%) were
      aware of the cancer risk from air pollution, but fewer (57.5%) were concerned
      about the risk caused by side-stream smoke. Most disagreed that lung cancer could
      be easily cured. Former smokers were more knowledgeable than current smokers
      about the health hazards of smoking, and those who never smoked were more
      knowledgeable than both. Engineering students were more likely to agree with the
      benefits of quitting smoking than were medical or science students. Addiction and
      friends were the reasons most frequently given for not quitting smoking.

PMID- 15980053
TI  - Caregiving to patients who are culturally diverse by Swedish last-year nursing
      students.
AB  - With Leininger's theory of cultural care diversity and universality as a
      framework, the aim of this study was to describe Swedish last-year nursing
      students' experiences of caregiving to patients who are culturally diverse. The
      students participated voluntarily, 107 by completing a questionnaire with open
      ended questions and 15 by participating in in-depth semistructured interviews.
      Three categories of experience were identified by use of qualitative method,
      namely, cultural awareness, cultural insufficiency, and cultural curiosity. The
      students were found to be on the level of Leininger's first phase of
      transcultural knowledge. It is concluded that cultural sensitivity should be
      promoted by integrating transcultural concepts into the curricula on all levels
      of nursing education and by offering special courses on transcultural nursing to
      nursing students and health care providers.

PMID- 15980054
TI  - Literature review: issues surrounding education of English-as-a-Second Language
      (ESL) nursing students.
AB  - Examined in this article are the challenges faced by English-as-a-Second Language
      (ESL) nursing students. Nursing faculties need to address these challenges to
      meet the increasing diversity of the health care system. A key concern is the
      ability of ESL nursing students to communicate effectively in English. The
      Cummins model for English language acquisition provides a template for ESL
      nursing students to bridge this communication barrier. The literature suggests
      some particular needs of ESL nursing students can be met through modification of
      nursing programs. Further research into factors affecting the quality of nursing
      education for ESL students is warranted. A quantitative analysis is required to
      see if there exists a positive correlation between improved English language
      acquisition and academic success by ESL nursing students.

PMID- 15980055
TI  - Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator
      activated receptor gamma contributes to the antifibrotic activity of FXR ligands
      in rodent models of liver cirrhosis.
AB  - The nuclear receptors farnesoid X receptor (FXR) and peroxisome proliferator
      activated receptor (PPAR)gamma exert counter-regulatory effects on hepatic
      stellate cells (HSCs) and protect against liver fibrosis development in rodents.
      Here, we investigated whether FXR ligands regulate PPARgamma expression in HSCs
      and models of liver fibrosis induced in rats by porcine serum and carbon
      tetrachloride administration and bile duct ligation. Our results demonstrate that
      HSCs trans-differentiation associated with suppression of PPARgamma mRNA
      expression, whereas FXR mRNA was unchanged. Exposure of cells to natural and
      synthetic ligands of FXR, including 6-ethyl chenodeoxycholic acid (6-ECDCA), a
      synthetic derivative of chenodeoxycholic acid, reversed this effect and increased
      PPARgamma mRNA by approximately 40-fold. Submaximally effective concentrations of
      FXR and PPARgamma ligands were additive in inhibiting alpha1(I) collagen mRNA
      accumulation induced by transforming growth factor (TGF)beta1. Administration of
      6-ECDCA in rats rendered cirrhotic by porcine serum and carbon tetrachloride
      administration or bile duct ligation reverted down-regulation of PPARgamma mRNA
      expression in HSCs. Cotreatment with 6-ECDCA potentiates the antifibrotic
      activity of rosiglitazone, a PPARgamma ligand, in the porcine serum model as
      measured by morphometric analysis of liver collagen content, hydroxyproline, and
      liver expression of alpha1(I) collagen mRNA, alpha-smooth muscle actin,
      fibronectin, TGFbeta1, and tissue inhibitor of metalloprotease 1 and 2, whereas
      it enhanced the expression of PPARgamma and uncoupling protein 2, a PPARgamma
      regulated gene, by 2-fold. In conclusion, by using an in vitro and in vivo
      approach, we demonstrated that FXR ligands up-regulate PPARgamma mRNA in HSCs and
      in rodent models of liver fibrosis. A FXR-PPARgamma cascade exerts counter
      regulatory effects in HSCs activation.

PMID- 15980056
TI  - Mechanisms underlying the effects of the pyrethroid tefluthrin on action
      potential duration in isolated rat ventricular myocytes.
AB  - Due to increased global use, acute exposures to pyrethroid insecticides in humans
      are of clinical concern. Pyrethroids have a primary mode of action that involves
      interference with the inactivation of Na+ currents (I(Na)) in excitable cells,
      which may include cardiac myocytes. To investigate the possible cardiac toxicity
      of these agents, we have examined the effects of a type-1 pyrethroid, tefluthrin,
      on isolated rat ventricular myocytes. Under whole-cell current-clamp, tefluthrin
      prolonged the mean action potential duration at 90% repolarization (APD90) by 216
      +/- 34% in 19 myocytes isolated from 14 hearts. About one-third of this
      prolongation was apparently due to persistent I(Na), with the balance associated
      with spontaneous cytosolic Ca2+ waves, and Na+-Ca2+ exchange. In some action
      potentials, tefluthrin also activated early after-depolarizations (EADs). Using a
      selected EAD-containing action potential clamp, we observed that EADs could evoke
      a Cd2+-sensitive membrane current (I(EAD)) that triggered secondary sarcoplasmic
      reticulum (SR) Ca2+ release. The notion that EADs could stimulate Ca2+ current
      was strengthened by the persistence of I(EAD) in myocytes exposed to
      extracellular Li+ and Sr2+ ions, used to minimize Na+-Ca2+ exchange and SR Ca2+
      release, respectively. Tefluthrin inhibited I(EAD) by approximately 10%.
      Together, our results support an arrhythmogenic model whereby tefluthrin exposure
      stimulated Na+ influx, provoking cellular Ca2+ overload by reverse Na+-Ca2+
      exchange. During Ca2+ waves, forward Na+-Ca2+ exchange prolonged the action
      potential markedly and kindled EADs by permitting the reactivation of Ca2+
      current. Similar mechanisms may be involved in pyrethroid toxicity in vivo, and
      also in type 3 long QT syndrome, wherein Na+ channel mutations prolong I(Na).

PMID- 15980057
TI  - Nanoparticles enhance therapeutic efficiency by selectively increased local drug
      dose in experimental colitis in rats.
AB  - Nanoparticles (NP) are proposed for targeted drug delivery to the inflammation
      site in severe cases of inflammatory bowel disease where state-of-the-art
      delivery devices fail. FK506 (tacrolimus) entrapped into NP was administered
      either orally or rectally to male Wistar rats suffering from a preexisting
      experimental colitis. Clinical activity score, colon/body weight index, and
      myeloperoxidase activity were determined to assess the inflammation. Tissue
      penetration experiments elucidated the processes involved in the proposed new
      therapeutic approach. The therapeutic effects of FK506 solutions as well as FK506
      NP by oral route were minor. The myeloperoxidase activity and colon/body weight
      ratio decreased significantly (P < 0.05) only after the rectal administration of
      FK506-NP, whereas treatment by free drug was not different from colitis control
      in both 2,4,6-trinitrobenzenesulfonic acid and oxazolone colitis model. NP allows
      an enhanced and selective drug penetration into the inflammation site as opposed
      to surrounding healthy tissue (healthy: FK506, 109 +/- 18 nmol/cm2; FK506-NP, 51
      +/- 13 nmol/cm2; colitis: FK506, 79 +/- 28 nmol/cm2; FK506-NP, 105 +/- 24
      nmol/cm2), presumably by protecting the encapsulated drug against influences from
      efflux systems and mucosal metabolism. The relative drug penetration into the
      inflamed tissue is about 3-fold higher compared with healthy tissue when using NP
      as drug carriers. The use of drug-loaded NP offers several advantages compared
      with standard therapeutic strategies such as a higher selectivity in adhesion to
      and enhanced drug penetration into the inflamed tissue.

PMID- 15980058
TI  - The effects of a selective dopamine D2 receptor agonist on behavioral and
      pathological outcome in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated
      squirrel monkeys.
AB  - In this study, we investigated antiparkinsonian activity of the novel, highly
      selective dopamine D(2) receptor agonist sumanirole compared with two clinically
      effective dopaminergic therapies in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) primate model of Parkinson's disease. Squirrel monkeys
      were rendered parkinsonian by chronic administration of MPTP and subsequently
      dosed with vehicle, L-DOPA plus carbidopa (L-DOPA), ropinirole, or sumanirole
      over a duration of 8 weeks. Antiparkinsonian effects measured with a parkinsonian
      primate rating scale (PPRS) showed that sumanirole elicited improved functional
      outcome compared with vehicle. The dopamine D2/D3 agonist ropinirole improved
      behavioral outcome similar to sumanirole, whereas L-DOPA treatment yielded the
      most significant symptomatic improvement. The relative rank of therapies that
      elicited normalization of PPRS was L-DOPA > sumanirole; ropinirole did not
      normalize PPRS in any of the treated monkeys. Dyskinesias were present with L
      DOPA treatment but were not observed in sumanirole-, ropinirole-, or placebo
      treated primates. Pathologically, all MPTP-treated animals displayed
      neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta
      and reactive astrocytosis. Neurons immunoreactive with antibodies to the nuclear
      transcription factor DeltaFosB were most significantly increased in the striatum
      of L-DOPA-treated monkeys. These results suggest that sumanirole can exert
      antiparkinsonian effects similar to L-DOPA without the behavioral and
      morphological consequences of the latter.

PMID- 15980059
TI  - Acetoacetate induces CYP2E1 protein and suppresses CYP2E1 mRNA in primary
      cultured rat hepatocytes.
AB  - The ketone body acetoacetate (AA) in the absence of insulin or in the presence of
      diabetic insulin levels decreases CYP2E1 mRNA expression in a concentration- and
      time-dependent manner in primary cultured rat hepatocytes. AA activates p70
      ribosomal S6 kinase (p70S6K) and protein kinase C (PKC) by approximately 2- to
      2.5-fold, respectively, following 6-h treatment. The AA-mediated activation of
      p70S6K, but not PKC, was abolished by inhibition of PI 3-K with LY294002 [2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or wortmannin, in agreement with
      p70S6K being downstream of phosphatidylinositol 3-kinase (PI 3-K). Inhibition of
      PI 3-K, mTOR with rapamycin, or PKC with bisindolylmaleimide ameliorated the AA
      mediated down-regulation of CYP2E1 mRNA expression. Neither the mitogen-activated
      protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) nor the p38
      mitogen-activated protein kinase inhibitor SB203580 [4-(4-fluorophenyl)-2-(4
      methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] ameliorated the AA-mediated
      suppression of CYP2E1 mRNA expression. Heterogeneous nuclear RNA analysis
      revealed that AA suppressed CYP2E1 gene transcription by approximately 50% and
      that inhibition of PI 3-K and PKC diminished this AA-mediated effect on
      transcription. CYP2E1 mRNA half-life slightly increased from approximately 24 h
      in untreated hepatocytes to approximately 32 h in AA-treated cells.
      Interestingly, AA increased CYP2E1 protein levels by approximately 2- and 2.5
      fold at 24 and 48 h, respectively. DL-beta-hydroxybutyrate was without effect.
      Polysomal distribution studies revealed that AA increased the proportion of RNA
      associated with the actively translated polysomal fractions versus the 40S to 60S
      untranslated fractions by approximately 40%. CYP2E1 protein half-life increased
      from approximately 8 h in untreated hepatocytes to approximately 24 in AA-treated
      cells. These data show that AA decreases CYP2E1 mRNA expression through
      inhibition of gene transcription while simultaneously elevating CYP2E1 protein
      levels through increased translation and decreased protein degradation.

PMID- 15980060
TI  - Sumanirole, a highly dopamine D2-selective receptor agonist: in vitro and in vivo
      pharmacological characterization and efficacy in animal models of Parkinson's
      disease.
AB  - The purpose of this study is to demonstrate that sumanirole is a novel dopamine
      receptor agonist with high in vitro and in vivo selectivity for the D(2) receptor
      subtype. Sumanirole, (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin
      2(1H)-one (Z)-2-butenedioate (1:1), is unique; it has greater than 200-fold
      selectivity for the D(2) receptor subtype versus the other dopamine receptor
      subtypes in radioligand binding assays. In cell-based assays, sumanirole is a
      fully efficacious agonist, with EC(50) values between 17 and 75 nM. In animals,
      sumanirole elicits many physiological responses attributed to D(2)-like receptor
      function. In rats, sumanirole is a full agonist for elevation of striatal
      acetylcholine levels (ED(50) = 12.1 micromol/kg i.p.). Sumanirole s.c. dose
      dependently decreased plasma prolactin levels and depressed dopamine neuron
      firing rates in the substantia nigra pars compacta with an ED(50) of 2.3
      micromol/kg i.v. This high selectivity for D(2) receptors translates into
      excellent locomotor stimulant activity in animal models of Parkinson's disease.
      In reserpinized, alpha-methyl-para-tyrosine-treated rats, sumanirole caused a
      significant and sustained increase in horizontal activity at doses > or =12.5
      micromol/kg s.c. In unilateral 6-hydroxydopamine-lesioned rats, sumanirole caused
      profound, sustained rotational behavior and was substantially more efficacious
      than any other agonist tested. Sumanirole-stimulated rotational behavior was
      blocked by the dopamine receptor antagonist haloperidol. Sumanirole dose
      dependently improved disability scores and locomotor activities of two of three 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In summary,
      sumanirole is the first published selective D(2) receptor agonist. The compound
      has activity in animal models of dopamine hypofunction and has a high level of
      efficacy in animal models of Parkinson's disease.

PMID- 15980061
TI  - Trends in mortality after hospital admission for liver cirrhosis in an English
      population from 1968 to 1999.
AB  - BACKGROUND: Population based mortality rates from liver cirrhosis, and alcohol
      consumption, have increased sharply in Britain in the past 35 years. Little is
      known about the long term trends over time in mortality rates after hospital
      admission for liver cirrhosis. AIMS: To analyse time trends in mortality in the
      year after admission for liver cirrhosis from 1968 to 1999. SUBJECTS: A total of
      8192 people who were admitted to hospital in a defined population of Southern
      England. METHODS: Analysis of hospital discharge statistics linked to death
      certificate data. The main outcome measures were case fatality rates (CFRs) and
      standardised mortality ratios (SMRs). RESULTS: At 30 days after admission, CFR
      was 15.9% and the SMR was 93 (86 in men and 102 in women, compared with 1 in the
      general population). At one year, the overall CFR was 33.6% and SMR was 16.3.
      There was no improvement from 1968 to 1999 in mortality rates. SMRs were highest
      for alcoholic cirrhosis of the liver (27.4 at one year) but lower for biliary
      cirrhosis (11.4) and chronic hepatitis (10.0). Mortality from most of the main
      causes of death, including accidents and suicides, was increased. CONCLUSIONS:
      The high mortality rates after hospital admission, and the fact that they have
      not fallen in the past 30 years, show that liver cirrhosis remains a disease with
      a very poor prognosis. Increased mortality from accidents, suicides, and mental
      disorders, particularly among those with alcoholic cirrhoses, indicates that
      prognosis is influenced by behavioural as well as by physical pathology.

PMID- 15980062
TI  - Regulation of the PIS1-encoded phosphatidylinositol synthase in Saccharomyces
      cerevisiae by zinc.
AB  - In the yeast Saccharomyces cerevisiae, the mineral zinc is essential for growth
      and metabolism. Depletion of zinc from the growth medium of wild type cells
      results in changes in phospholipid metabolism, including an increase in
      phosphatidylinositol content (Iwanyshyn, W. M., Han, G.-S., and Carman, G. M.
      (2004) J. Biol. Chem. 279, 21976-21983). We examined the effects of zinc
      depletion on the regulation of the PIS1-encoded phosphatidylinositol synthase,
      the enzyme that catalyzes the formation of phosphatidylinositol from CDP
      diacylglycerol and inositol. Phosphatidylinositol synthase activity increased
      when zinc was depleted from the growth medium. Analysis of a zrt1Delta zrt2Delta
      mutant defective in plasma membrane zinc transport indicated that the cytoplasmic
      levels of zinc were responsible for the regulation of phosphatidylinositol
      synthase. PIS1 mRNA, its encoded protein Pis1p, and the beta-galactosidase
      activity driven by the P(PIS1)-lacZ reporter gene were elevated in zinc-depleted
      cells. This indicated that the increase in phosphatidylinositol synthase activity
      was the result of a transcriptional mechanism. The zinc-mediated induction of the
      P(PIS1)-lacZ reporter gene, Pis1p, and phosphatidylinositol synthase activity was
      lost in zap1Delta mutant cells. These data indicated that the regulation of PIS1
      gene expression by zinc depletion was mediated by the zinc-regulated
      transcription factor Zap1p. Direct interaction between glutathione S-transferase
      (GST)-Zap1p(687-880) and a putative upstream activating sequence (UAS) zinc
      responsive element in the PIS1 promoter was demonstrated by electrophoretic
      mobility shift assays. Mutations in the UAS zinc-responsive element in the PIS1
      promoter abolished the GST-Zap1p(687-880)-DNA interaction in vitro and abolished
      the zinc-mediated regulation of the PIS1 gene in vivo. This work advances
      understanding of phospholipid synthesis regulation by zinc and the transcription
      control of the PIS1 gene.

PMID- 15980063
TI  - Domain swapping between Enterococcus faecalis FabN and FabZ proteins localizes
      the structural determinants for isomerase activity.
AB  - Anaerobic unsaturated fatty acid synthesis in bacteria occurs through the
      introduction of a double bond into the growing acyl chain. In the Escherichia
      coli model system, FabA catalyzes both the dehydration of beta-hydroxydecanoyl
      ACP and the isomerization of trans-2-decenoyl-ACP to cis-3-decenoyl-ACP as the
      essential step. A second dehydratase, FabZ, functions in acyl chain elongation
      but cannot carry out the isomerization reaction. Enterococcus faecalis has two
      highly related FabZ homologs. One of these, termed EfFabN, carries out the
      isomerization reaction in vivo, whereas the other, EfFabZ, does not (Wang, H.,
      and Cronan, J. E. (2004) J. Biol. Chem. 279, 34489-34495). We carried out a
      series of domain swapping and mutagenesis experiments coupled with in vitro
      biochemical analyses to define the structural feature(s) that specify the
      catalytic properties of these two enzymes. Substitution of the beta3 and beta4
      strands of EfFabZ with the corresponding strands from EfFabN was necessary and
      sufficient to convert EfFabZ into an isomerase. These data are consistent with
      the hypothesis that the isomerase potential of beta-hydroxyacyl-ACP dehydratases
      is determined by the properties of the beta-sheets that dictate the orientation
      of the central alpha-helix and thus the shape of the substrate binding tunnel
      rather than the catalytic machinery at the active site.

PMID- 15980064
TI  - The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein
      kinase kinases.
AB  - The AMP-activated protein kinase (AMPK) is an important regulator of cellular
      metabolism in response to metabolic stress and to other regulatory signals. AMPK
      activity is absolutely dependent upon phosphorylation of AMPKalphaThr-172 in its
      activation loop by one or more AMPK kinases (AMPKKs). The tumor suppressor
      kinase, LKB1, is a major AMPKK present in a variety of tissues and cells, but
      several lines of evidence point to the existence of other AMPKKs. We have
      employed three cell lines deficient in LKB1 to study AMPK regulation and
      phosphorylation, HeLa, A549, and murine embryo fibroblasts derived from LKB(-/-)
      mice. In HeLa and A549 cells, mannitol, 2-deoxyglucose, and ionomycin, but not 5
      aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), treatment activates
      AMPK by alphaThr-172 phosphorylation. These responses, as well as the downstream
      effects of AMPK on the phosphorylation of acetyl-CoA carboxylase, are largely
      inhibited by the Ca(2+)/ calmodulin-dependent protein kinase kinase (CaMKK)
      inhibitor, STO-609. AMPKK activity in HeLa cell lysates measured in vitro is
      totally inhibited by STO-609 with an IC50 comparable with that of the known CaMKK
      isoforms, CaMKKalpha and CaMKKbeta. Furthermore, 2-deoxyglucose- and ionomycin
      stimulated AMPK activity, alphaThr-172 phosphorylation, and acetyl-CoA
      carboxylase phosphorylation are substantially reduced in HeLa cells transfected
      with small interfering RNAs specific for CaMKKalpha and CaMKKbeta. Lastly, the
      activation of AMPK in response to ionomycin and 2-deoxyglucose is not impaired in
      LKB1(-/-) murine embryo fibroblasts. These data indicate that the CaMKKs function
      in intact cells as AMPKKs, predicting wider roles for these kinases in regulating
      AMPK activity in vivo.

PMID- 15980065
TI  - Membrane fusion induced by neuronal SNAREs transits through hemifusion.
AB  - Synaptic transmission requires the controlled release of neurotransmitter from
      synaptic vesicles by membrane fusion with the presynaptic plasma membrane. SNAREs
      are the core constituents of the protein machinery responsible for synaptic
      membrane fusion. The mechanism by which SNAREs drive membrane fusion is thought
      to involve a hemifusion intermediate, a condition in which the outer leaflets of
      two bilayers are combined and the inner leaflets remain intact; however,
      hemifusion has been observed only as an end point rather than as an intermediate.
      Here, we examined the kinetics of membrane fusion of liposomes mediated by
      recombinant neuronal SNAREs using fluorescence assays that monitor both total
      lipid mixing and inner leaflet mixing. Our results demonstrate that hemifusion is
      dominant at the early stage of the fusion reaction. Over time, hemifusion
      transitioned to complete fusion, showing that hemifusion is a true intermediate.
      We also show that hemifusion intermediates can be trapped, likely as unproductive
      outcomes, by modulating the surface concentration of the SNARE proteins.

PMID- 15980066
TI  - Ser-557-phosphorylated mCRY2 is degraded upon synergistic phosphorylation by
      glycogen synthase kinase-3 beta.
AB  - Cryptochrome 1 and 2 act as essential components of the central and peripheral
      circadian clocks for generation of circadian rhythms in mammals. Here we show
      that mouse cryptochrome 2 (mCRY2) is phosphorylated at Ser-557 in the liver, a
      well characterized peripheral clock tissue. The Ser-557-phosphorylated form
      accumulates in the liver during the night in parallel with mCRY2 protein, and the
      phosphorylated form reaches its maximal level at late night, preceding the peak
      time of the protein abundance by approximately 4 h in both light-dark cycle and
      constant dark conditions. The Ser-557-phosphorylated form of mCRY2 is localized
      in the nucleus, whereas mCRY2 protein is located in both the cytoplasm and
      nucleus. Importantly, phosphorylation of mCRY2 at Ser-557 allows subsequent
      phosphorylation at Ser-553 by glycogen synthase kinase-3beta (GSK-3beta),
      resulting in efficient degradation of mCRY2 by a proteasome pathway. As assessed
      by phosphorylation of GSK-3beta at Ser-9, which negatively regulates the kinase
      activity, GSK-3beta exhibits a circadian rhythm in its activity with a peak from
      late night to early morning when Ser-557 of mCRY2 is highly phosphorylated.
      Altogether, the present study demonstrates an important role of sequential
      phosphorylation at Ser-557/Ser-553 for destabilization of mCRY2 and illustrates a
      model that the circadian regulation of mCRY2 phosphorylation contributes to
      rhythmic degradation of mCRY2 protein.

PMID- 15980067
TI  - The YoeB toxin is a folded protein that forms a physical complex with the
      unfolded YefM antitoxin. Implications for a structural-based differential
      stability of toxin-antitoxin systems.
AB  - The chromosomal YoeB-YefM toxin-antitoxin module common to numerous strains of
      bacteria is presumed to have a significant role in survival under stringent
      conditions. Recently we showed that the purified YefM antitoxin is a natively
      unfolded protein, as we previously reported for the Phd antitoxin in the P1 phage
      Doc-Phd toxin-antitoxin system. Here we report the purification and structural
      properties of the YoeB toxin and present physical evidence for the existence of a
      tight YoeB. YefM polypeptide complex in solution. YoeB and YefM proteins co
      eluted as single peaks in sequential Ni-affinity FPLC and Q-Sepharose ion
      exchange chromatography implying the formation of a YoeB. YefM complex. The
      unstable antitoxin was removed from the mixture by natural proteolysis, and the
      residual YoeB protein was purified using ion exchange chromatography.
      Fluorescence anisotropy studies of the purified YoeB and YefM proteins showed a
      2:1 stoichiometry of the complex, providing direct evidence for a physical
      complex between the proteins. Near- and far-UV circular dichroism spectroscopy of
      the purified toxin revealed that, similar to the Doc toxin, YoeB is a well-folded
      protein. Thermal denaturation experiments confirmed the conformational stability
      of the YoeB toxin, which underwent reversible thermal unfolding at temperatures
      up to 56 degrees C. The thermodynamic features of the toxin-antitoxin complex
      were similar. Taken together, our results support the notion of a correlation
      between differential physiological and structural stability in toxin-antitoxin
      modules.

PMID- 15980068
TI  - Hepatitis C virus NS2/3 processing is required for NS3 stability and viral RNA
      replication.
AB  - The hepatitis C virus NS2/3 protease is responsible for cleavage of the viral
      polyprotein between nonstructural proteins NS2 and NS3. We show here that
      mutation of three highly conserved residues in NS2 (His(952), Glu(972), and
      Cys(993)) abrogates NS2/3 protease activity and that introduction of any of these
      mutations into subgenomic NS2-5B replicons results in complete inactivation of
      NS2/3 processing and RNA replication in both stable and transient replication
      assays. The effect of uncleaved NS2 on the various activities of NS3 was
      therefore explored. Unprocessed NS2 had no significant effect on the in vitro
      ATPase and helicase activities of NS3, whereas immunoprecipitation experiments
      demonstrated a decreased affinity of NS4A for uncleaved NS2/3 as compared with
      NS3. This subsequently resulted in reduced kinetics in an in vitro NS3 protease
      assay with the unprocessed NS2/3 protein. Interestingly, NS3 was still capable of
      efficient processing of the polyprotein expressed from a subgenomic replicon in
      Huh-7 cells in the presence of uncleaved NS2. Notably, we show that fusion with
      NS2 leads to the rapid degradation of NS3, whose activity is essential for RNA
      replication. Finally, we demonstrate that uncleaved NS2/3 degradation can be
      prevented by the addition of a proteasome inhibitor. We therefore propose that
      NS2/3 processing is a critical step in the viral life cycle and is required to
      permit the accumulation of sufficient NS3 for RNA replication to occur. The
      regulation of NS2/3 cleavage could constitute a novel mechanism of switching
      between viral RNA replication and other processes of the hepatitis C virus life
      cycle.

PMID- 15980070
TI  - A proteoglycan undergoes different modifications en route to the apical and
      basolateral surfaces of Madin-Darby canine kidney cells.
AB  - We have grown polarized epithelial Madin-Darby canine kidney II (MDCK II) cells
      on filters in the presence of [(35)S]sulfate, [(3)H]glucosamine, or
      [(35)S]cysteine/[(35)S]methionine to study proteoglycan (PG) synthesis, sorting,
      and secretion to the apical and basolateral media. Whereas most of the
      [(35)S]sulfate label was recovered in basolateral PGs, the [(3)H]glucosamine
      label was predominantly incorporated into the glycosaminoglycan chains of apical
      PGs, indicating that basolateral PGs are more intensely sulfated than their
      apical counterparts. Expression of the PG serglycin with a green fluorescent
      protein tag (SG-GFP) in MDCK II cells produced a protein core secreted 85%
      apically, which was largely modified by chondroitin sulfate chains. Surprisingly,
      the 15% of secreted SG-GFP molecules recovered basolaterally were more heavily
      sulfated and displayed a different sulfation pattern than the apical counterpart.
      More detailed studies of the differential modification of apically and
      basolaterally secreted SG-GFP indicate that the protein cores have been
      designated to apical and basolateral transport platforms before pathway-specific,
      post-translational modifications have been completed.

PMID- 15980069
TI  - The C-terminal domain of the nucleotide-binding domain protein Wzt determines
      substrate specificity in the ATP-binding cassette transporter for the
      lipopolysaccharide O-antigens in Escherichia coli serotypes O8 and O9a.
AB  - The polymannan O-antigenic polysaccharides (O-PSs) of Escherichia coli O8 and O9a
      are synthesized via an ATP-binding cassette (ABC) transporter-dependent pathway.
      The group 2 capsular polysaccharides of E. coli serve as prototypes for
      polysaccharide synthesis and export via this pathway. Here, we show that there
      are some fundamental differences between the ABC transporter-dependent pathway
      for O-PS biosynthesis and the capsular polysaccharide paradigm. In the capsule
      system, mutants lacking the ABC transporter are viable, and membranes isolated
      from these strains are no longer able to synthesize polymer using an endogenous
      acceptor. In contrast, E. coli strains carrying mutations in the membrane
      component (Wzm) and/or the nucleotide-binding component (Wzt) of the O8 and O9a
      polymannan transporters are nonviable under conditions permissive to O-PS
      biosynthesis and take on an aberrant elongated cell morphology. Whereas the ABC
      transporters for capsular polysaccharides with different structures are
      functionally interchangeable, the O8 and O9a exporters are specific for their
      cognate polymannan substrates. The E. coli O8 and O9a Wzt proteins contain a C
      terminal domain not present in the corresponding nucleotide-binding protein
      (KpsT) from the capsule exporter. Whereas the Wzm components are functionally
      interchangeable, albeit with reduced efficiency, the Wzt components are not,
      indicating a specific role for Wzt in substrate specificity. Chimeric Wzt
      proteins were constructed in order to localize the region involved in substrate
      specificity to the C-terminal domain.

PMID- 15980071
TI  - Differential regulation of dentin sialophosphoprotein expression by Runx2 during
      odontoblast cytodifferentiation.
AB  - Dentin sialophosphoprotein (DSPP) consists of dentin sialoprotein (DSP) and
      dentin phosphoprotein (DPP). The spatial-temporal expression of DSPP is largely
      restricted during differentiational stages of dental cells. DSPP plays a vital
      role in tooth development. It is known that an osteoblast-specific transcription
      factor, Runx2, is essential for osteoblast differentiation. However, effects of
      Runx2 on DSPP transcription remain unknown. Here, we studied different roles of
      Runx2 in controlling DSPP expression in mouse preodontoblast (MD10-F2) and
      odontoblast (MO6-G3) cells. Two Runx2 isoforms were expressed in preodontoblast
      and odontoblast cells, and in situ hybridization assay showed that DSPP
      expression increased, whereas Runx2 was down-regulated during odontoblast
      differentiation and maturation. Three potential Runx2 sites are present in
      promoters of mouse and rat DSPP genes. Runx2 binds to these sites as demonstrated
      by electrophoretic mobility shift assay and supershift experiments. Mutations of
      Runx2 sites in mouse DSPP promoter resulted in a decline of promoter activity in
      MD10-F2 cells compared with an increase of its activity in MO6-G3 cells. Multiple
      Runx2 sites were more active than a single site in regulating the DSPP promoter.
      Furthermore, forced overexpression of Runx2 isoforms induced increases of
      endogenous DSPP protein levels in MD10-F2 cells but reduced its expression in MO6
      G3 cells consistent with the DSPP promoter analysis. Thus, our results suggest
      that differential positive and negative regulation of DSPP by Runx2 is dependent
      on use of cytodifferentiation of dental ectomesenchymal-derived cells that may
      contribute to the spatial-temporal expression of DSPP during tooth development.

PMID- 15980072
TI  - Fibrillin-1 interactions with heparin. Implications for microfibril and elastic
      fiber assembly.
AB  - Fibrillin-1 assembly into microfibrils and elastic fiber formation involves
      interactions with glycosaminoglycans. We have used BIAcore technology to
      investigate fibrillin-1 interactions with heparin and with heparin saccharides
      that are analogous to S-domains of heparan sulfate. We have identified four high
      affinity heparin-binding sites on fibrillin-1, localized three of these sites,
      and defined their binding kinetics. Heparin binding to the fibrillin-1 N terminus
      has particularly rapid kinetics. Hyaluronan and chondroitin sulfate did not
      interact significantly with fibrillin-1. Heparin saccharides with more than 12
      monosaccharide units bound strongly to all four fibrillin-1 sites. Heparin did
      not inhibit fibrillin-1 N- and C-terminal interactions or RGD-dependent cell
      attachment, but heparin and MAGP-1 competed for binding to the fibrillin-1 N
      terminus, and heparin and tropoelastin competed for binding to a central
      fibrillin-1 sequence. By regulating these key interactions, heparin can
      profoundly influence microfibril and elastic fiber assembly.

PMID- 15980073
TI  - The Small GTPase RalA controls exocytosis of large dense core secretory granules
      by interacting with ARF6-dependent phospholipase D1.
AB  - RalA and RalB constitute a family of highly similar Ras-related GTPases widely
      distributed in different tissues. Recently, active forms of Ral proteins have
      been shown to bind to the exocyst complex, implicating them in the regulation of
      cellular secretion. Since RalA is present on the plasma membrane in
      neuroendocrine chromaffin and PC12 cells, we investigated the potential role of
      RalA in calcium-regulated exocytotic secretion. We show here that endogenous RalA
      is activated during exocytosis. Expression of the constitutively active RalA
      (G23V) mutant enhances secretagogue-evoked secretion from PC12 cells. Conversely,
      expression of the constitutively inactive GDP-bound RalA (G26A) or silencing of
      the RalA gene by RNA interference led to a strong impairment of the exocytotic
      response. RalA was found to co-localize with phospholipase D1 (PLD1) at the
      plasma membrane in PC12 cells. We demonstrate that cell stimulation triggers a
      direct interaction between RalA and ARF6-activated PLD1. Moreover, reduction of
      endogenous RalA expression level interfered with the activation of PLD1 observed
      in secretagogue-stimulated cells. Finally, using various RalA mutants selectively
      impaired in their ability to activate downstream effectors, we show that PLD1
      activation is essential for the activation of secretion by GTP-loaded RalA.
      Together, these results provide evidence that RalA is a positive regulator of
      calcium-evoked exocytosis of large dense core secretory granules and suggest that
      stimulation of PLD1 and consequent changes in plasma membrane phospholipid
      composition is the major function RalA undertakes in calcium-regulated
      exocytosis.

PMID- 15980075
TI  - Predicting older adults' maintenance in exercise participation using an
      integrated social psychological model.
AB  - Little is known about the predictors of maintenance in organized exercise
      programmes. The aim of this study was to investigate the behavioral predictors of
      maintenance of exercise participation in older adults, using an integrated social
      psychological model. To this end, we carried out a prospective cohort study (n =
      1,725; age 50 years or older) involving 10 different types of exercise
      programmes, with measurements at baseline and after 6 months. Predictors of
      intention to continue participating and the actual maintenance of exercise
      participation in the exercise programme were assessed using a step-wise logistic
      regression model. Significant odds ratios (ORs) predicting the intention to
      continue with the exercise programme were found for female sex, younger age,
      being married, being a non-smoker, being in paid employment, having a positive
      attitude towards exercise and having a high self-efficacy at baseline.
      Significant ORs predicting actual maintenance of exercise participation were
      short lapses, absence of lapses, high intention at baseline, high perceived
      quality of the programme, positive attitude at baseline and few risk situations
      at baseline. In order to promote maintenance of exercise participation for older
      adults, effort should be taken to prevent lapses, to help people cope with risk
      situations for lapses, to improve the attitude towards exercise participation and
      to improve the quality of the programme.

PMID- 15980076
TI  - Redesigning clinical education: a major challenge for academic health centers.

PMID- 15980077
TI  - Negotiating end-of-life decision making: a comparison of Japanese and U.S.
      residents' approaches.
AB  - PURPOSE: To compare Japanese and U.S. resident physicians' attitudes, clinical
      experiences, and emotional responses regarding making disclosures to patients
      facing incurable illnesses. METHOD: From September 2003 to June 2004, the authors
      used a ten-item self-administered anonymous questionnaire in a cross-sectional
      survey of 103 internal medicine residents at two U.S. sites in Los Angeles,
      California, and 244 general medical practice residents at five Japanese sites in
      Central Honshu, Kyushu, Okinawa, Japan. RESULTS: The Japanese residents were more
      likely to favor including the family in disclosing diagnosis (95% versus 45%,
      p<.001) and prognosis (95% versus 51%, p<.001) of metastatic gastric cancer. Of
      residents who favored diagnostic or prognostic disclosure to both the patient and
      family, Japanese residents were more likely to prefer discussion with the family
      first. Trainees in Japan expressed greater uncertainty about ethical practices
      related to disclosure of diagnosis or prognosis. Many Japanese and U.S. residents
      indicated that they had deceived a patient at the request of a family (76% versus
      18 %, p<.001), or provided nonbeneficial care (56% versus 72%, p<.05), and many
      expressed guilt about these behaviors. CONCLUSIONS: The residents' approaches to
      end-of-life decision making reflect known cultural preferences related to the
      role of patients and their families. Although Japanese trainees were more likely
      to endorse the role of the family, they expressed greater uncertainty about their
      approach. Difficulty and uncertainty in end-of-life decision making were common
      among both the Japanese and U.S. residents. Both groups would benefit from
      ethical training to negotiate diverse, changing norms regarding end-of-life
      decision making.

PMID- 15980078
TI  - Residents' end-of-life decision making with adult hospitalized patients: a review
      of the literature.
AB  - PURPOSE: The authors performed a structured literature review to understand
      residents' experiences with end-of-life (EOL) decision making with adult
      hospitalized patients, specifically regarding decisions to withhold or withdraw
      advanced life-support measures. METHOD: An Ovid-based strategy was used to search
      Medline, ERIC, PsychINFO, and CINHAL databases for articles published between
      1966 and February 2005, combining the domains of "resuscitation orders,"
      "decision making," and "internship and residency." All quantitative and
      qualitative studies examining residents' EOL decision making with adult
      hospitalized patients were included. The authors developed and applied a scoring
      system for relevance and quality, performed data abstraction and quality
      assessment independently and in duplicate, then met to collate findings and
      identify factors in residents' EOL decision making. RESULTS: The searches yielded
      884 articles, of which 26 were included. Variable methodologies precluded meta
      analysis. In these studies, residents felt unprepared to handle patient EOL
      decision making, although exposure to EOL discussions helped them gain
      confidence. Residents' attitudes, skills, and knowledge were key determinants of
      whether EOL decisions were addressed. Many misinterpreted the terms "DNR" and
      "futility." Residents' understanding of the patient EOL decision-making process
      could be extremely variable, and their do-not-resuscitate discussions suboptimal.
      Residents' lived practice experience of the patient EOL decision-making process
      was often at odds with what they were taught in formal curricula. CONCLUSIONS:
      Educational strategies aimed at changing residents' knowledge, skills and
      attitude should address the hidden curriculum for the patient EOL decision-making
      process that is part of the experienced culture of every day practice. Future
      studies of this experienced culture would inform specific educational
      interventions.

PMID- 15980079
TI  - "This is just too awful; I just can't believe I experienced that...": medical
      students' reactions to their "most memorable" patient death.
AB  - PURPOSE: To examine medical students' emotional reactions to their "most
      memorable" patient death and the support they receive. METHOD: In 2000-01, 65
      third-year medical students at two Northeastern U.S. medical schools were
      randomly selected to participate in 60-90-minute interviews of open-ended and
      structured questions and a written questionnaire (using a ten-point scale) about
      their "most memorable" patient death. Independent reviewers coded each interview
      to identify the analytical categories. Descriptive data were generated from the
      written questionnaire. RESULTS: A total of 32 interviews were used in the
      analysis. Twelve (38%) students were in contact with the patient for less than 24
      hours and 23 (73%) were not at all or minimally close to the patient (0-3 on ten
      point scale). Sixteen of 28 students (57%) rated the impact of the death as
      highly emotionally powerful (7-10 on ten-point scale). The finality of deaths,
      particularly sudden deaths, evoked strong emotions. Four of 16 (25%) students who
      found the death highly emotionally powerful rated the amount of support from
      supervisors as extremely inadequate (0-3 on ten-point scale). There was no
      discussion of the death in 17 (63%) of the 27 cases in which the patient was
      cared for by the student's team. Students perceived from supervising physicians
      that death and emotions are negative aspects of medicine. CONCLUSIONS: Medical
      students experienced patient deaths as emotionally powerful even when they were
      not close to the patients. Debriefing sessions with students were rare, and many
      students felt inadequately supported. Thus, a unique opportunity to teach about
      death, emotions and coping with stress is often lost.

PMID- 15980080
TI  - Third-year medical students' experiences with dying patients during the internal
      medicine clerkship: a qualitative study of the informal curriculum.
AB  - PURPOSE: To explore third-year medical students' experiences with death and dying
      patients during the first internal medicine clerkship. METHOD: In August 2002,
      through purposeful sampling, the authors targeted for open-ended interviews 32
      third-year medical students at the University of California, San Francisco in the
      first core internal medicine clerkship. Interviews averaged 45 minutes in length
      and were audiotaped, transcribed, and analyzed using a grounded theory approach.
      RESULTS: Twenty-eight (87.5%) students participated in interviews. All students
      encountered death or dying patients, and most cared directly for at least one
      dying patient. Students' relationships with patients were characterized by
      attachment, empathy, and advocacy. Students valued preparation by preclinical end
      of-life (EOL) courses, but assigned greater value to patient care experiences
      guided by teams that acknowledged deaths, role-modeled EOL care, and respected
      students' participation in patient care. Clerkship experiences in EOL care
      affected students' developing professional identities by affording opportunities
      to manage strong emotions, understand the challenges of transitioning to
      residency, and gain a sense of self-efficacy as future physicians providing EOL
      care. CONCLUSIONS: Third-year medical students' experiences with dying patients
      affect their skills and attitudes in EOL care, as well as the emergence of their
      professional identities. The behaviors and attitudes modeled by residents and
      attendings during the clerkships can strongly influence students' perceptions of
      and self-efficacy in EOL care. Further research and interventions into how
      residents and attendings model responses to death in the clinical clerkship may
      suggest strategies not only for EOL training, but also for mentoring professional
      development.

PMID- 15980081
TI  - "It was haunting...": physicians' descriptions of emotionally powerful patient
      deaths.
AB  - PURPOSE: To understand the emotional experiences of physicians who care for dying
      patients and to identify educational opportunities for improving patient care and
      physician well-being. METHOD: Between 1999-2001, physicians at two quaternary
      care medical centers in Boston, Massachusetts, and Pittsburgh, Pennsylvania,
      participated in 90-minute, semistructured personal interviews on their most
      emotionally powerful patient death. Quantitative data was obtained through face
      to-face surveys rated on ten-point scales that asked physicians about emotional
      characteristics of and emotional responses to the death. In the qualitative
      portion of the survey, physicians were asked to describe the details of the most
      emotionally powerful patient death, the types and sequence of their emotional
      reactions, their methods of coping, and subsequent changes in behavior. RESULTS:
      Physicians had powerful experiences with death during all stages of their
      careers. Experiences with patient death generally fit into one of three types:
      "good," "overtreated," or "shocking/unexpected." Housestaff often described
      coping in isolation with the disturbing emotions generated in the care of dying
      patients. Physicians learned how to care for and cope with dying patients from
      their experiences with patients whose deaths were most emotionally powerful and
      reported changes in their clinical behavior and career paths as a result.
      CONCLUSIONS: Physicians' emotional reactions to patient death can affect patient
      care and the personal lives of physicians. Supervising physicians have an
      opportunity to improve both the care of dying patients and house-staff coping
      with these deaths by using the "teachable moments" that are present for trainees
      as they care for the dying.

PMID- 15980082
TI  - Teaching and learning end-of-life care: evaluation of a faculty development
      program in palliative care.
AB  - PURPOSE: To evaluate the effectiveness of the Program in Palliative Care
      Education and Practice (PCEP), an intensive faculty development program at
      Harvard Medical School. METHOD: PCEP is a two-week program offered annually with
      two on-site sessions in Boston, MA, and an interim period distance-learning
      component. Training integrates palliative care clinical skill development,
      learning theory and teaching methods, and leadership and organizational change.
      Longitudinal surveys (preprogram, retrospective preprogram, and postprogram) of
      participants from 2000-03 assessed self-reported preparation in providing and
      teaching palliative care; teaching and patient care practices; and satisfaction
      with program. RESULTS: The response rate was 96% (n=149) for Session I and 72%
      for both Session I and II (n=113). Questionnaire responses demonstrated
      statistically significant improvements with large effect sizes (range 0.7-1.8) on
      nearly all measures. Preparation increased from 3.0+/-1.1 to 4.2+/-0.7 for
      providing end-of-life care (1=not well prepared, 5=very well prepared), and from
      2.6+/-1.0 to 4.3+/-0.7 for teaching this topic. Respondents reported behavioral
      changes in patient care and teaching; e.g., after the program, 63% noted that,
      specifically as a result of attending the course, they encouraged learners to
      reflect on their emotional responses to dying patients, and 57% conducted
      experiential exercises (e.g., role-play). Eighty-two percent rated the experience
      as "transformative," and many responses to open-ended items described powerful
      learning experiences. Participants rated the program highly (4.9+/-0.1, 1=lowest,
      5=highest rating). CONCLUSIONS: Integrating clinical content with learning about
      educational methods is an efficient and effective approach to enhancing clinical
      faculty's capacity to model and teach clinical care. This program offers an
      educational model that engages practitioners, stimulates changes in practice, and
      offers opportunities for reflection and professional revitalization.

PMID- 15980083
TI  - The palliative care clinical evaluation exercise (CEX): an experience-based
      intervention for teaching end-of-life communication skills.
AB  - PURPOSE: To pilot test the "Palliative Care Clinical Evaluation Exercise (CEX),"
      a new experience-based intervention to teach communication skills in giving bad
      news and discussing code status. The intervention allows faculty to observe,
      evaluate, and give feedback to housestaff in their discussions with patients and
      families. METHOD: In 2002-03, the intervention was piloted among 60 first-year
      residents in the categorical Internal Medicine Residency Programs at the
      University of Pittsburgh. The authors collected feasibility measurements at the
      time of intervention, and interns' attitudes were measured before and one week
      after intervention and at the end of the intern year. RESULTS: Forty-four
      residents (73%) completed the intervention. Discussions averaged a total of 49.5
      minutes (SD 24.1), divided among 12.7 minutes (SD 7.5) for prediscussion
      counseling between the resident and faculty observer, 25.6 minutes (SD 16.1) for
      the resident-patient discussion, and 12.1 minutes (SD 5.7) for postdiscussion
      feedback. Residents rated the Palliative Care CEX favorably (>3 on a five-point
      scale) on ease of arranging the exercise, educational value, quality of the
      experience, effect on their comfort with discussions, importance to their
      education, and value of preceptor feedback. Self-ratings of communication
      competence showed improvement one week after the intervention. CONCLUSIONS: The
      Palliative Care CEX is feasible and positively valued by residents. The findings
      from this initial pilot study support the value of further efforts to refine the
      intervention, to confirm its feasibility in other settings, and to validate its
      use as an educational and assessment tool.

PMID- 15980084
TI  - Blindness.

PMID- 15980086
TI  - How can physicians' learning styles drive educational planning?
AB  - As changes in health care delivery systems and in the global burden of disease
      call for a reassessment of how tomorrow's physicians should be educated--indeed,
      for a reconsideration of the diversity of roles the physician should play--there
      is an immediate need to produce continuing medical education (CME) programs with
      real impact. Curriculum planners are questioning both the content of medical
      education and the methods of instruction and training. The product, or content,
      and the mechanism for its delivery have been defined and discussed, but a
      significant body of literature has shown that new knowledge does not necessarily
      lead to new behavior. Ample evidence exists in the CME literature to support the
      implementation of more active and self-directed learning strategies to promote
      the desired change in behaviors. The question, then, that is the focus of this
      article is how educational planning might be better guided by an understanding of
      how physicians learn within the continuing medical education domain. Revisiting
      the principles of David Kolb's Learning Styles Inventory, the authors propose
      applying his experiential learning model to overall curriculum design work. The
      authors argue that promoting the application of all learning styles in sequence
      in an educational encounter is a most desirable approach, and that this approach
      to learning could extend far beyond individual learners to influence how every
      component of medical education is designed, from the individual lecture or class
      activity to entire courses or programs.

PMID- 15980087
TI  - Teaching evidence-based medicine: should we be teaching information management
      instead?
AB  - To encourage high-quality patient care guided by the best evidence, many medical
      schools and residencies are teaching techniques for critically evaluating the
      medical literature. While a large step forward, these skills of evidence-based
      medicine are necessary but not sufficient for the practice of contemporary
      medicine. Incorporating the best evidence into the real world of busy clinical
      practice requires the applied science of information management. Clinicians must
      learn the techniques and skills to focus on finding, evaluating, and using
      information at the point of care. This information must be both relevant to
      themselves and their patients as well as being valid. The authors discuss the
      need to teach the applied science of information management along with, or
      perhaps even instead of, teaching the basic science of evidence-based medicine.
      All students, residents, and practicing physicians need three skills to practice
      the best medicine: the ability to select foraging--"keeping up"--tools that
      filter information for relevance and validity, the skill to select and use a
      hunting--"just in time"--information tool that presents prefiltered information
      easily and in a quickly accessible form at the point of care, and the ability to
      make decisions by combining the best patient-oriented evidence with patient
      centered care, placing the evidence in perspective with the needs and desires of
      the patient. This teaching of information management skills will prepare students
      and residents for a practice of medicine that requires lifelong learning.

PMID- 15980088
TI  - Responsibly managing the medical school--teaching hospital power relationship.
AB  - The relationship between medical schools and their teaching hospitals involves a
      complex and variable mixture of monopoly and monopsony power, which has not been
      previously been ethically analyzed. As a consequence, there is currently no
      ethical framework to guide leaders of both institutions in the responsible
      management of this complex power relationship. The authors define these two forms
      of power and, using economic concepts, analyze the nature of such power in the
      medical school-teaching hospital relationship, emphasizing the potential for
      exploitation. Using concepts from both business ethics and medical ethics, the
      authors analyze the nature of transparency and co-fiduciary responsibility in
      this relationship. On the basis of both rational self-interest, drawn from
      business ethics, and co-fiduciary responsibility, drawn from medical ethics, they
      argue for the centrality of transparency in the medical school-teaching hospital
      relationship. Understanding the ethics of monopoly and monopsony power is
      essential for the responsible management of the complex relationship between
      medical schools and their teaching hospitals and can assist the leadership of
      academic health centers in carrying out one of their major responsibilities: to
      prevent the exploitation of monopoly power and monopsony power in this
      relationship.

PMID- 15980089
TI  - Self-reflection in multicultural training: be careful what you ask for.
AB  - Self-reflection in multicultural education is an important means to develop self
      awareness and ultimately to change professional behavior in favor of more
      equitable health care to diverse populations. As conceptualized by scholars in
      the field of psychology, racial identity theory is critical to understanding and
      planning for the potentially wide range of predictable reactions to provocative
      activities, including those negative reactions that do not necessarily herald a
      flaw in programming. Careful consideration of racial identity developmental
      phases can also assist program planners to optimally meet the needs of individual
      physician trainees in their ongoing constructive professional and personal
      development, and in strategically mobilizing and having ready the type of
      institutional leadership that supports trainees' change processes. The authors
      focus on white physician trainees, the largest racial group of U.S. physicians
      and medical students. They first explain what they mean by the terms white and
      nonwhite. Racial identity theory is then applied, with true case examples, to
      explore such issues as where the self-proclaimed "color-blind" trainee fits into
      this theoretical schema, and how medical educators can best serve trainees who
      are resistant or indifferent to discussions of racism in medicine and equity in
      health care delivery. Ultimately, the authors' goal is to demonstrate that
      engendering genuine self-reflection can substantively improve the delivery of
      health care to the nation's diverse population. To help achieve that goal, they
      emphasize what to anticipate in effecting optimal trainee education and how to
      create an institutional climate supportive of individual change.

PMID- 15980090
TI  - The irony of osteopathic medicine and primary care.
AB  - Osteopathic medicine is strongly identified with primary care. In the past 20
      years, several factors have influenced this relationship, resulting in
      significant changes in the postdoctoral training of doctors of osteopathic
      medicine (DOs). Growth in colleges of osteopathic medicine spilled over into
      postdoctoral programs of the Accreditation Council for Graduate Medical Education
      (ACGME), creating a number of consequences. More than ever, osteopathic
      physicians are filling voids in ACGME primary care residency positions left
      vacant by U.S. medical graduates. Many allopathic primary care residencies have
      created parallel-accredited (American Osteopathic Association/ACGME) programs in
      hopes of tapping into this supply of DOs. In turn, osteopathic training
      institutions have shifted their educational emphasis in support of nonprimary
      care residencies. As a result of these changes, there is a strong element of
      irony in the underlying reasons for osteopathic medicine's link to primary care,
      why osteopathic training institutions are emphasizing specialty residencies, and
      the new responsibility of allopathic programs in training the next generation of
      primary care DOs.

PMID- 15980091
TI  - Resident teaching: a tale of two places in time.

PMID- 15980092
TI  - Considering the culture of disability in cultural competence education.
AB  - Cultural competence extends beyond understanding those values, beliefs, and needs
      that are associated with patients' age or gender or with their racial, ethnic, or
      religious backgrounds. People hold many simultaneous cultural associations, and
      each have implications for the care process. The "culture of disability" is a pan
      ethnic culture for which a set of physician competencies are required to ensure
      appropriate, culturally sensitive care to persons with congenital or acquired
      disabilities. Such competencies include communicating with patients who have
      deficits in verbal communication and avoidance of infantilizing speech;
      understanding the values and needs of persons with disabilities; the ability to
      encourage self-advocacy skills of patients and families; acknowledging the core
      values of disability culture including the emphasis on interdependence rather
      than independence; and feeling comfortable with patients with complex
      disabilities. Medical schools have developed programs to increase students'
      exposure to persons with disabilities and it is suggested that such programs are
      most effective when they are the result of collaboration with community-based
      facilities or organizations that serve persons with disabilities in the natural
      environment. Combining lecture-based instruction and structured experiences with
      the opportunity for students to interact with patients in their natural
      environments may facilitate development of competencies with respect to patients
      with disabilities. The culture of disability should be included as one of the
      many cultures addressed in cultural competence initiatives in medical school and
      residency curricula.

PMID- 15980093
TI  - Colicins prevent colonization of urinary catheters.
AB  - OBJECTIVES: Natural microbial defence systems, such as bacteriocins, may be a
      novel means to prevent catheter-associated urinary tract infection. We
      investigated in vitro whether a colicin-expressing strain of Escherichia coli
      could prevent urinary catheter colonization by a colicin-susceptible,
      uropathgenic strain of E. coli. METHODS: Segments of urinary catheter were
      inoculated with colicin-producing E. coli K-12 and then exposed to either colicin
      susceptible E. coli (a uropathogenic clinical isolate) or colicin-resistant E.
      coli (derived from the susceptible clinical isolate). Catheters were then
      incubated overnight, rinsed and sonicated. RESULTS: The presence of colicin
      producing E. coli K-12 on the catheter surface completely prevented catheter
      colonization by colicin-susceptible E. coli but not by resistant E. coli. The
      colicin-susceptible strain but not the colicin-resistant strain also disappeared
      from broth cultures in the presence of colicin-producing E. coli K-12.
      CONCLUSIONS: The observed inhibition of catheter colonization by the
      uropathogenic clinical isolate of E. coli can be attributed to the presence of a
      colicin-producing strain of E. coli on the catheter surface. Bacteriocin
      production by a non-pathogenic organism may have clinical applicability as a
      means to prevent catheter-associated urinary tract infection.

PMID- 15980095
TI  - Duration of antibiotic treatment: are even numbers odd?

PMID- 15980096
TI  - Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs.
AB  - It is imperative to continue efforts to identify novel effective therapies that
      can assist in containing the spread of HIV. Recently acquired knowledge about the
      HIV entry process points to new strategies to block viral entry. For most HIV
      strains, the successful infection of their target cells is mainly dependent on
      the presence of the CD4 surface molecule, which serves as the primary virus
      receptor. The attachment of the viral envelope to this cellular CD4 receptor can
      be considered as an ideal target with multiple windows of opportunity for
      therapeutic intervention. Therefore, drugs that interfere with the CD4 receptor,
      and thus inhibit viral entry, may be promising agents for the treatment of AIDS.
      The CD4-targeted HIV entry inhibitors cyclotriazadisulfonamides represent a novel
      class of small molecule antiviral agents with a unique mode of action. The lead
      compound, CADA, specifically interacts with the cellular CD4 receptor and is
      active against a wide variety of HIV strains at submicromolar levels when
      evaluated in different cell-types such as T cells, monocytes and dendritic cells.
      Moreover, a strict correlation has been demonstrated between anti-HIV activity
      and CD4 interaction of about 20 different CADA analogues. In addition, CADA acted
      synergistically in combination with all other FDA-approved anti-HIV drugs as well
      as with compounds that target the main HIV co-receptors. In this article, the
      characteristics of cyclotriazadisulfonamide compounds are presented and the
      possible application of CADA as a microbicide is also discussed.

PMID- 15980094
TI  - Comparative assessment of antibiotic susceptibility of coagulase-negative
      staphylococci in biofilm versus planktonic culture as assessed by bacterial
      enumeration or rapid XTT colorimetry.
AB  - OBJECTIVES: To quantitatively compare the antibiotic susceptibility of biofilms
      formed by the coagulase-negative staphylococci (CoNS) Staphylococcus epidermidis
      and Staphylococcus haemolyticus with the susceptibility of planktonic cultures.
      METHODS: Several CoNS strains were grown planktonically or as biofilms to
      determine the effect of the mode of growth on the level of susceptibility to
      antibiotics with different mechanisms of action. The utility of a new, rapid
      colorimetric method that is based on the reduction of a tetrazolium salt (XTT) to
      measure cell viability was tested by comparison with standard bacterial
      enumeration techniques. A 6 h kinetic study was performed using dicloxacillin,
      cefazolin, vancomycin, tetracycline and rifampicin at the peak serum
      concentration of each antibiotic. RESULTS: In planktonic cells, inhibitors of
      cell wall synthesis were highly effective over a 3 h period. Biofilms were much
      less susceptible than planktonic cultures to all antibiotics tested, particularly
      inhibitors of cell wall synthesis. The susceptibility to inhibitors of protein
      and RNA synthesis was affected by the biofilm phenotype to a lesser degree.
      Standard bacterial enumeration techniques and the XTT method produced equivalent
      results both in biofilms and planktonic assays. CONCLUSIONS: This study provides
      a more accurate comparison between the antibiotic susceptibilities of planktonic
      versus biofilm populations, because the cell densities in the two populations
      were similar and because we measured the concentration required to inhibit
      bacterial metabolism rather than to eradicate the entire bacterial population.
      While the biofilm phenotype is highly resistant to antibiotics that target cell
      wall synthesis, it is fairly susceptible to antibiotics that target RNA and
      protein synthesis.

PMID- 15980097
TI  - Staphylococcal tetracycline-MLSB resistance plasmid pSTE2 is the product of an
      RSA-mediated in vivo recombination.
AB  - OBJECTIVES: The complete nucleotide sequence of the 6913 bp plasmid pSTE2 from
      Staphylococcus lentus, which mediates inducible resistance to tetracyclines,
      macrolides and lincosamides, was determined. The plasmid was analysed for
      potential reading frames and structural features to gain insight into its
      development from potential ancestor plasmids. METHODS: Plasmid pSTE2 was
      transformed into Staphylococcus aureus RN4220. Suitable restriction fragments
      were cloned into E. coli plasmid vectors and sequenced. In vitro susceptibility
      testing was performed to confirm the resistance phenotype mediated by this
      plasmid. RESULTS: Plasmid pSTE2 consisted of two parts, each of which
      corresponded closely to previously identified staphylococcal plasmids. The
      initial 4439 bp represented a pT181-analogous tet(K)-carrying tetracycline
      resistance plasmid, whereas the remaining 2474 bp represented a pPV141-related
      erm(C)-carrying macrolide-lincosamide-streptogramin B resistance plasmid. Both
      putative parental plasmids harboured the staphylococcal recombination site A
      (RSA) and the pT181-like plasmid also carried the recombinase gene pre whose
      product acts at RSA. Analysis of the junctions of the pT181-like and the pPV141
      like homologous parts in pSTE2 suggested that plasmid pSTE2 developed from pT181-
      and pPV141-like ancestor plasmids by cointegrate formation at RSA. CONCLUSION:
      Plasmid pSTE2 is the first completely sequenced plasmid from S. lentus and
      represents the product of an in vivo derived RSA-mediated recombination between
      two compatible plasmids.

PMID- 15980098
TI  - Global analysis of IL-2 target genes: identification of chromosomal clusters of
      expressed genes.
AB  - T lymphocytes play a central role in controlling adaptive immune responses. IL-2
      critically regulates both T cell growth and death and is involved in maintaining
      peripheral tolerance, but the molecules involved in these and other IL-2 actions
      are only partially known. We now provide a comprehensive compendium of the genes
      expressed in T cells and of those regulated by IL-2 based on a combination of DNA
      microarrays and serial analysis of gene expression (SAGE). The newly identified
      IL-2 target genes include many genes previously linked to apoptosis in other
      cellular systems that may contribute to IL-2-dependent survival functions. We
      also studied the mRNA expression of known regulators of signaling pathways for
      their induction in response to IL-2 in order to identify potential novel positive
      and/or negative feedback regulators of IL-2 signaling. We show that IL-2
      regulates only a limited number of these genes. These include suppressors of
      cytokine signaling (SOCS) 1, SOCS2, dual-specificity phosphatase (DUSP) 5, DUSP6
      and non-receptor type phosphatase-7 (PTPN7). Additionally, we provide evidence
      that many genes expressed in T cells locate in chromosomal clusters, and that
      select IL-2-regulated genes are located in at least two clusters, one at 5q31, a
      known cytokine gene cluster, and the other at 6p21.3, a region that contains
      genes encoding the tumor necrosis factor (TNF) superfamily members TNF, LT-alpha
      and LT-beta.

PMID- 15980099
TI  - Metabolism of the one-ring open metabolites of the cardioprotective drug
      dexrazoxane to its active metal-chelating form in the rat.
AB  - Dexrazoxane (ICRF-187) is clinically used as a doxorubicin cardioprotective agent
      and may act by preventing iron-based oxygen free radical damage through the iron
      chelating ability of its fully hydrolyzed metabolite ADR-925 (N,N'-[(1S)-1-methyl
      1,2-ethanediyl]-bis[(N-(2-amino-2-oxoethyl)]glycine). Dexrazoxane undergoes
      initial metabolism to its two one-ring open intermediates and is then further
      metabolized to its active metal ion-binding form ADR-925. The metabolism of these
      intermediates to the ring-opened metal-chelating product ADR-925 has been
      determined in a rat model to identify the mechanism by which dexrazoxane is
      activated. The plasma concentrations of both intermediates rapidly decreased
      after their i.v. administration to rats. A maximum concentration of ADR-925 was
      detected 2 min after i.v. bolus administration, indicating that these
      intermediates were both rapidly metabolized in vivo to ADR-925. The kinetics of
      the initial appearance of ADR-925 was consistent with formation rate-limited
      metabolism of the intermediates. After administration of dexrazoxane or its two
      intermediates, ADR-925 was detected in significant levels in both heart and liver
      tissue but was undetectable in brain tissue. The rapid rate of metabolism of the
      intermediates was consistent with their hydrolysis by tissue dihydroorotase. The
      rapid appearance of ADR-925 in plasma may make ADR-925 available to be taken up
      by heart tissue and bind free iron. These studies showed that the two one-ring
      open metabolites of dexrazoxane were rapidly metabolized in the rat to ADR-925,
      and thus, these results provide a mechanism by which dexrazoxane is activated to
      its active metal-binding form.

PMID- 15980100
TI  - Bimolecular fluorescence complementation analysis of cytochrome p450 2c2, 2e1,
      and NADPH-cytochrome p450 reductase molecular interactions in living cells.
AB  - Interactions between cytochromes P450 (P450s) and P450 reductase are required for
      enzymatic activity, and homo- or heterooligomerization of P450s may also be
      functionally important. Bimolecular fluorescence complementation (BiFC) was used
      to examine P450 interactions in a natural membrane context within living cells.
      BiFC detects protein interactions in living cells by reconstitution of a
      fluorescent protein from two fragments that are fused to the two interacting
      proteins. Nonspecific protein-protein interactions were detected if proteins were
      expressed at high levels. At low protein expression levels, homo-oligomerization
      of P450 2C2, but not P450 2E1, and interactions of these P450s with P450
      reductase were detected by BiFC, consistent with interactions detected previously
      by fluorescence resonance emission transfer. Weak interaction of P450 2C2 with
      P450 2E1 and homooligomerization of P450 reductase was also detected by BiFC.
      Homo-oligomerization of the N-terminal P450 2C1 signal anchor sequence and
      interactions between the signal anchor and full-length P450 2C2 were detected,
      suggesting that homo-oligomerization of P450 2C2 is mediated by the signal
      anchor. However, interactions between the signal anchor and either P450 2E1 or
      P450 reductase were not detected by BiFC. Although high concentrations of the
      substrate lauric acid increased BiFC for both P450 2E1 and P450 2C2 with P450
      reductase, the concentration dependence did not correlate with reported K(m)
      values. These results demonstrate that BiFC is an effective method to study the
      complex protein interactions that occur within the microsomal P450 system in
      living cells.

PMID- 15980101
TI  - Udp-glucuronosyltransferase 2b7 is the major enzyme responsible for gemcabene
      glucuronidation in human liver microsomes.
AB  - The predominant metabolic pathway of gemcabene in humans is glucuronidation. The
      principal human UDP-glucuronosyltransferases (UGTs) involved in the
      glucuronidation of gemcabene were determined in this study. Glucuronidation of
      gemcabene was catalyzed by recombinant UGT1A3, recombinant UGT2B7, and
      recombinant UGT2B17, as well as by human liver microsomes (HLM). Gemcabene
      glucuronidation in recombinant UGTs and HLM followed non-Michaelis-Menten
      kinetics consistent with homotropic activation, but pharmacokinetics in humans
      were linear over the dose range tested (total plasma C(max), 0.06-0.88 mM).
      Gemcabene showed similar affinity (S(50)) for recombinant UGTs (0.92-1.45 mM) and
      HLM (1.37 mM). S-Flurbiprofen was identified as a more selective inhibitor of
      recombinant UGT2B7-catalyzed gemcabene glucuronidation (>23-fold lower IC(50))
      when compared with recombinant UGT1A3- or recombinant UGT2B17-catalyzed gemcabene
      glucuronidation. The IC(50) for S-flurbiprofen inhibition of gemcabene
      glucuronidation was similar in HLM (60.6 microM) compared with recombinant UGT2B7
      (27.4 microM), consistent with a major role for UGT2B7 in gemcabene
      glucuronidation in HLM. In addition, 5,6,7,3',4',5'-hexamethoxyflavone inhibited
      recombinant UGT1A3 and recombinant UGT2B17-catalyzed gemcabene glucuronidation
      (with 4-fold greater potency for recombinant UGT1A3) but did not inhibit
      gemcabene glucuronidation in HLM, suggesting that UGT1A3 and UGT2B17 do not
      contribute significantly to gemcabene glucuronidation. Reaction rates for
      gemcabene glucuronidation from a human liver bank correlated well (r(2)=0.722,
      P<0.0001; n=24) with rates of glucuronidation of the UGT2B7 probe substrate 3'
      azido-3'-deoxythymidine. In conclusion, using the three independent experimental
      approaches typically used for cytochrome P450 reaction phenotyping, UGT2B7 is the
      major enzyme contributing to gemcabene glucuronidation in human liver microsomes.

PMID- 15980102
TI  - Metabolism and disposition of a potent group II metabotropic glutamate receptor
      agonist, in rats, dogs, and monkeys.
AB  - Metabolism and disposition of MGS0028 [(1R,2S,5S,6S)-2-amino-6-fluoro-4
      oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid monohydrate], a potent group II
      metabotropic glutamate receptor agonist, were examined in three preclinical
      species (Sprague-Dawley rats, beagle dogs, and rhesus monkeys). In rats, MGS0028
      was widely distributed and primarily excreted in urine as parent and as a single
      reductive metabolite, identified as the 4R-isomer MGS0034 [(1R,2S,4R,5S,6S)-2
      amino-6-fluoro-4-hydroxybicyclo[3.1.0]-hexane-2,6-dicarboxylic acid]. MGS0028 had
      a low brain to plasma ratio at efficacious doses in rats and was eliminated more
      slowly in rat brain than in plasma. Exposure increased proportionally (1--10
      mg/kg p.o.) in rats, with bioavailability>60% at all doses. However,
      bioavailability was only approximately 20% in monkeys, and MGS0034 was found in
      relatively high abundance in plasma. In dogs, oral bioavailability was >60%, and
      the metabolite was not detected. In vitro metabolism was examined in liver
      subcellular fractions (microsomes and cytosol) from rat, dog, monkey, and human.
      Reductive metabolism was observed in rat, monkey, and human liver cytosol
      incubations, but not in dog liver cytosol incubations. No metabolism of MGS0028
      was detected in incubations with liver microsomes from any species. Similar to in
      vivo results, MGS0028 was reduced in cytosol stereospecifically to MGS0034. The
      rank order of in vitro metabolite formation (monkey >> rat approximately human >>
      dog) was in agreement with in vivo observations in rats, dogs, and monkeys. Based
      on the observation of species difference in reductive metabolism, rat and monkey
      were recommended to be the preclinical species for further characterization prior
      to testing in humans. Finally, allometric scaling predicts that human
      pharmacokinetic parameters would be acceptable for further development.

PMID- 15980103
TI  - Isoform-specific expression and induction of udp-glucuronosyltransferase in
      immunoactivated peritoneal macrophages of the rat.
AB  - Phase I drug-metabolizing enzymes such as cytochrome P450 in immunocytes are
      known to play a role in metabolic activation of toxic and immunosuppressive
      compounds such as polycyclic aromatic hydrocarbon (PAH). UDP
      glucuronosyltransferase (UGT), a drug-metabolizing phase II enzyme, accelerates
      elimination of these compounds; however, there is little information on the
      expression and function of UGT in immunocytes. In this study, we investigated the
      expressions of UGT isoforms in rat peritoneal macrophages and the role of UGT in
      macrophage functions. Expressions of UGT1A1, 1A6, and 1A7 were observed in
      macrophages by immunohistochemical staining and reverse transcriptase-polymerase
      chain reaction. When macrophage cells cultured in plates were exposed to 1
      naphthol and 3-hydroxybenzo-[a]pyrene (3-OH-B[a]P), these glucuronides increased
      in the medium, indicating that macrophages glucuronidated the chemicals. The
      production of the glucuronides of 1-naphthol and 3-OH-B[a]P was induced by
      lipopolysaccharide (LPS) treatment of the cultured macrophage cells. Northern
      blot analysis revealed that UGT1A7 mRNA was induced by LPS treatment. This result
      is the first evidence that a drug-metabolizing enzyme is induced by
      immunoactivation. The results indicated that macrophages can detoxify various
      toxic and immunosuppressive compounds with UGT, and that ability is enhanced by
      immunoactivation. We propose that macrophages contribute to protection against
      not only macromolecules as immunocytes but also small molecules such as the
      immunosuppressive agents PAHs in peripheral blood and interstitial tissues.

PMID- 15980104
TI  - Cyp2a6 is a principal enzyme involved in hydroxylation of 1,7-dimethylxanthine, a
      main caffeine metabolite, in humans.
AB  - In a caffeine test previously performed with healthy Japanese volunteers, we
      found that the CYP1A2 index defined as urinary {5-acetylamino-6-amine-3
      methyluracil (AAMU)+1-methylxanthine (1X)+1-methyluric acid (1 U)}/1,7
      dimethyluric acid (17 U) was affected by the whole deleted allele of CYP2A6
      (CYP2A6*4). Since the high value of the CYP1A2 index could be caused by a low
      urinary concentration of 17 U, we postulated that CYP2A6 was responsible for the
      1,7-dimethylxanthine (17 X) metabolism to generate 17 U (17 X 8-hydroxylation).
      Thus, the role of CYP2A6 in the 17 X 8-hydroxylation was fully examined in the
      present study. Among 10 isoforms of human cytochrome P450 (CYP1A2, CYP2A6,
      CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, or CYP3A5) expressed in
      Escherichia coli cells, CYP2A6 and CYP1A2 showed high catalytic activities for
      the 17 X 8-hydroxylation. The 17 X 8-hydroxylase activities significantly
      associated with coumarin 7-hydroxylase activities (r=0.67, p<0.01) in liver
      microsomes from 17 individuals, but not with ethoxyresorufin O-deethylase
      activities. Tranylcypromine, an inhibitor of CYP2A6, reduced the 17 X 8
      hydroxylase activities of human liver microsomes. The 17 X 8-hydroxylase
      activities of CYP2A6.7, CYP2A6.10, and CYP2A6.11 expressed in E. coli cells were
      12, 13, and 22% of that of CYP2A6.1, respectively. The 17 X 8-hydroxylase
      activities were found to be low in liver microsomes from individuals possessing
      the deletion or mutations in the CYP2A6 gene. Based on these data, we conclude
      that CYP2A6 is a main 17 X 8-hydroxylase and that the catalytic activities for
      the 17 X 8-hydroxylation are reduced by the genetic polymorphisms of the CYP2A6
      gene.

PMID- 15980105
TI  - Atrial overdrive pacing for sleep apnea: a door now closed?

PMID- 15980107
TI  - The sound of one hand clapping: tuberculosis and antiretroviral therapy in
      Africa.

PMID- 15980108
TI  - Can studies of the early bactericidal activity of rifapentine tell us how to
      prevent acquired rifamycin-resistant relapse?

PMID- 15980109
TI  - And the beat goes on.

PMID- 15980112
TI  - Should we start considering surfactant for atelectasis?

PMID- 15980113
TI  - Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS)
      due to a novel mutation in the MCT8 thyroid hormone transporter.
AB  - We report a novel 1 bp deletion (c.1834delC) in the MCT8 gene in a large
      Brazilian family with Allan-Herndon-Dudley syndrome (AHDS), an X linked condition
      characterised by severe mental retardation and neurological dysfunction. The
      c.1834delC segregates with the disease in this family and it was not present in
      100 control chromosomes, further confirming its pathogenicity. This mutation
      causes a frameshift and the inclusion of 64 additional amino acids in the C
      terminal region of the protein. Pathogenic mutations in the MCT8 gene, which
      encodes a thyroid hormone transporter, results in elevated serum triiodothyronine
      (T3) levels, which were confirmed in four affected males of this family, while
      normal levels were found among obligate carriers. Through in vitro functional
      assays, we showed that this mutation decreases cellular T3 uptake and
      intracellular T3 metabolism. Therefore, the severe neurological defects present
      in the patients are due not only to deficiency of intracellular T3, but also to
      altered metabolism of T3 in central neurones. In addition, the severe muscle
      hypoplasia observed in most AHDS patients may be a consequence of high serum T3
      levels.

PMID- 15980114
TI  - Age associated increase in the prevalence of chromosome 22q loss of
      heterozygosity in histological subsets of benign meningioma.
AB  - Chromosome 22q loss of heterozygosity (LOH) is the most common allelic loss in
      benign meningioma and is thought to be the earliest initiating event in
      meningioma formation. We used published data and logistic regression to evaluate
      the association of 22q LOH with age at diagnosis in 318 transitional,
      fibroblastic, and meningothelial meningiomas. After adjustment for anatomical
      location, the odds ratio of 22q LOH per year of age was >1 in each histological
      type of meningioma, and was significantly >1 in transitional and fibroblastic
      meningioma. This finding is compatible with involvement of the neurofibromatosis
      2 tumour suppressor gene, NF2, on chromosome 22q in the high incidence of benign
      meningioma in the elderly.

PMID- 15980115
TI  - Breakpoints around the HOXD cluster result in various limb malformations.
AB  - BACKGROUND: Characterisation of disease associated balanced chromosome
      rearrangements is a promising starting point in the search for candidate genes
      and regulatory elements. METHODS: We have identified and investigated three
      patients with limb abnormalities and breakpoints involving chromosome 2q31.
      Patient 1 with severe brachydactyly and syndactyly, mental retardation,
      hypoplasia of the cerebellum, scoliosis, and ectopic anus, carries a balanced
      t(2;10)(q31.1;q26.3) translocation. Patient 2, with translocation
      t(2;10)(q31.1;q23.33), has aplasia of the ulna, shortening of the radius, finger
      anomalies, and scoliosis. Patient 3 carries a pericentric inversion of chromosome
      2, inv(2)(p15q31). Her phenotype is characterised by bilateral aplasia of the
      fibula and the radius, bilateral hypoplasia of the ulna, unossified carpal bones,
      and hypoplasia and dislocation of both tibiae. RESULTS: By fluorescence in situ
      hybridisation, we have mapped the breakpoints to intervals of approximately 170
      kb or less. None of the three 2q31 breakpoints, which all mapped close to the
      HOXD cluster, disrupted any known genes. CONCLUSIONS: Hoxd gene expression in the
      mouse is regulated by cis-acting DNA elements acting over distances of several
      hundred kilobases. Moreover, Hoxd genes play an established role in bone
      development. It is therefore very likely that the three rearrangements disturb
      normal HOXD gene regulation by position effects.

PMID- 15980116
TI  - Array-CGH detection of micro rearrangements in mentally retarded individuals:
      clinical significance of imbalances present both in affected children and normal
      parents.
AB  - BACKGROUND: The underlying causes of mental retardation remain unknown in about
      half the cases. Recent array-CGH studies demonstrated cryptic imbalances in about
      25% of patients previously thought to be chromosomally normal. OBJECTIVE AND
      METHODS: Array-CGH with approximately 3500 large insert clones spaced at
      approximately 1 Mb intervals was used to investigate DNA copy number changes in
      81 mentally impaired individuals. RESULTS: Imbalances never observed in control
      chromosomes were detected in 20 patients (25%): seven were de novo, nine were
      inherited, and four could not have their origin determined. Six other alterations
      detected by array were disregarded because they were shown by FISH either to
      hybridise to both homologues similarly in a presumptive deletion (one case) or to
      involve clones that hybridised to multiple sites (five cases). All de novo
      imbalances were assumed to be causally related to the abnormal phenotypes. Among
      the others, a causal relation between the rearrangements and an aberrant
      phenotype could be inferred in six cases, including two imbalances of the X
      chromosome, where the associated clinical features segregated as X linked
      recessive traits. CONCLUSIONS: In all, 13 of 81 patients (16%) were found to have
      chromosomal imbalances probably related to their clinical features. The clinical
      significance of the seven remaining imbalances remains unclear. The limited
      ability to differentiate between inherited copy number variations which cause
      abnormal phenotypes and rare variants unrelated to clinical alterations currently
      constitutes a limitation in the use of CGH-microarray for guiding genetic
      counselling.

PMID- 15980119
TI  - Histological analysis of fetal dopamine cell suspension grafts in two patients
      with Parkinson's disease gives promising results.

PMID- 15980131
TI  - BVA AWF: considering the impact of the draft Animal Welfare Bill.

PMID- 15980132
TI  - Improving education for undergraduates.

PMID- 15980134
TI  - Financial incentive to control paratuberculosis (Johne's disease) on dairy farms
      in the United Kingdom.
AB  - This paper estimates the financial incentive to control paratuberculosis on dairy
      farms by establishing the level of expenditure that would minimise the total cost
      of the disease (output losses plus control expenditure). Given the late onset of
      the clinical signs and the lack of treatments, control was focused on minimising
      the financial impact of paratuberculosis by adjusting the dairy cow replacement
      policy. The optimum replacement policies for disease-free herds and infected
      herds were compared by using dynamic programming. At the standard settings, the
      disease justified adjusting the culling policy; under constant bioeconomic
      assumptions, it reduced the expected annuity from milk production under the
      optimal replacement policy by about 10 per cent (27 pounds sterling per cow
      annually), a considerably lower figure than for other major endemic diseases that
      affect dairy cows in the uk. The effect was even less at lower milk prices,
      suggesting that there is at present little incentive for dairy farmers to put
      more resources into controlling the disease. However, the incentive could be
      increased if more information were available about how best to manage the disease
      under specific farm circumstances. Any effect that paratuberculosis may have on
      the future demand for milk and hence on milk prices would also be an important
      consideration.

PMID- 15980135
TI  - Influence of the calcium content of the diet offered to leopard tortoises
      (Geochelone pardalis).
AB  - Twenty-four juvenile leopard tortoises were divided into four groups of six; one
      group was fed a basic low-calcium feed for six months, and the other three groups
      were fed the same basic diet supplemented with one, three and nine times the
      amount of calcium recommended as a supplement to the diet of reptiles. The
      animals' bone mineral content and bone mineral density were estimated by dual
      energy x-ray absorptiometry, and blood samples were taken at the start and at the
      conclusion of the study. One tortoise from each group was examined postmortem.
      There was a clear depletion of calcium in the body of the tortoises receiving no
      calcium supplement, and the shell of the tortoises receiving the recommended
      calcium supplement did not calcify to the extent expected. The tortoises that
      received three times the recommended calcium supplementation had the highest
      growth rate and were thriving. However, metastatic calcifications were observed
      postmortem in the two groups that were given the highest doses of calcium.

PMID- 15980136
TI  - Control of endoparasites in horses with a gel containing moxidectin and
      praziquantel.
AB  - A gel formulation containing moxidectin (20 g/kg) and praziquantel (125 g/kg)
      reduced the geometric mean faecal strongyle egg count in horses to below 100 eggs
      per gram of faeces (epg) for at least 12 weeks despite their being exposed
      continuously to reinfection from pasture grazed by treated and untreated horses.
      The geometric mean egg count of horses treated with a proprietary paste
      containing abamectin (3.7 g/kg) and praziquantel (46.2 g/kg) increased steadily
      from six weeks after the treatment, peaking at over 820 epg after 12 weeks.
      Relative to the efficacy of the abamectin/praziquantel treatment, the reduction
      in mean faecal egg count compared with the pretreatment counts was significantly
      (P<0.05) better in the horses treated with moxidectin and praziquantel from eight
      weeks after the treatment. Both products eliminated tapeworms from horses in a
      non-invasive modified critical trial.

PMID- 15980137
TI  - Plasma thrombin-antithrombin complex concentrations in dogs with malignant
      tumours.

PMID- 15980138
TI  - Canine distemper in local dogs in Nsukka, Nigeria.

PMID- 15980139
TI  - Extraskeletal myxoid chondrosarcoma in a cow.

PMID- 15980140
TI  - Cystic dilation of the teat sinuses in doe goats.

PMID- 15980141
TI  - Diagnosis of preclinical scrapie in samples of rectal mucosa.

PMID- 15980144
TI  - FMD and the contiguous cull.

PMID- 15980146
TI  - Symptoms or signs?

PMID- 15980147
TI  - A database analysis method identifies an endogenous trans-acting short
      interfering RNA that targets the Arabidopsis ARF2, ARF3, and ARF4 genes.
AB  - Two classes of small RNAs, microRNAs and short-interfering RNA (siRNAs), have
      been extensively studied in plants and animals. In Arabidopsis, the capacity to
      uncover previously uncharacterized small RNAs by means of conventional strategies
      seems to be reaching its limits. To discover new plant small RNAs, we developed a
      protocol to mine an Arabidopsis nonannotated, noncoding EST database. Using this
      approach, we identified an endogenous small RNA, trans-acting short-interfering
      RNA-auxin response factor (tasiR-ARF), that shares a 21- and 22-nt region of
      sequence similarity with members of the ARF gene family. tasiR-ARF has
      characteristics of both short-interfering RNA and microRNA, recently defined as
      tasiRNA. Accumulation of trans-acting siRNA depends on DICER-LIKE1 and RNA
      DEPENDENT RNA POLYMERASE6 but not RNA-DEPENDENT RNA POLYMERASE2. We demonstrate
      that tasiR-ARF targets three ARF genes, ARF2, ARF3/ETT, and ARF4, and that both
      the tasiR-ARF precursor and its target genes are evolutionarily conserved. The
      identification of tasiRNA-ARF as a low-abundance, previously uncharacterized
      small RNA species proves our method to be a useful tool to uncover additional
      small regulatory RNAs.

PMID- 15980148
TI  - Increasing the power of functional maps of the medial temporal lobe by using
      large deformation diffeomorphic metric mapping.
AB  - The functional magnetic resonance imagery responses of declarative memory tasks
      in the medial temporal lobe (MTL) are examined by using large deformation
      diffeomorphic metric mapping (LDDMM) to remove anatomical variations across
      subjects. LDDMM is used to map the structures of the MTL in multiple subjects
      into extrinsic atlas coordinates; these same diffeomorphic mappings are used to
      transfer the corresponding functional data activation to the same extrinsic
      coordinates. The statistical power in the averaged LDDMM mapped signals is
      significantly increased over conventional Talairach-Tournoux averaging.
      Activation patterns are highly localized within the MTL. Whereas the present
      demonstration has been aimed at enhancing alignment within the MTL, this
      technique is general and can be applied throughout the brain.

PMID- 15980149
TI  - Central memory self/tumor-reactive CD8+ T cells confer superior antitumor
      immunity compared with effector memory T cells.
AB  - Central memory CD8+ T cells (T(CM)) and effector memory CD8+ T cells (T(EM)) are
      found in humans and mice; however, their relative contributions to host immunity
      have only recently been examined in vivo. Further, the ability of T(CM) to treat
      an established tumor or infection has yet to be evaluated. To address the
      therapeutic potential of different tumor-reactive CD8+ T cell memory subsets, we
      used an established model for the in vitro generation of T(CM) and T(EM) by using
      IL-15 and IL-2, respectively. Adoptively transferred T(CM) exhibited a potent in
      vivo recall response when combined with tumor-antigen vaccination and exogenous
      IL-2, leading to the eradication of large established tumors. By contrast, T(EM)
      were far less effective on a per-cell basis. Microarray analysis revealed that
      the signature of highly in vivo effective antitumor T cells included the
      overexpression of genes responsible for trafficking to secondary lymphoid
      tissues. This gene expression profile correctly predicted the in vitro and in
      vivo lymphoid-homing attributes of tumor-reactive T cells. Furthermore, we found
      that homing to secondary lymphoid tissue is required for optimal tumor treatment.
      Our findings indicated that highly in vivo effective antitumor T cells were those
      that initially targeted secondary lymphoid tissue, rather than tumor sites, as
      had previously been postulated. Thus, tumor-reactive CD8+ T cell populations with
      the phenotypic and functional attributes of T(CM) may be superior to
      T(EM)/effector T cells for adoptive immunotherapies using concomitant tumor
      antigen vaccination.

PMID- 15980152
TI  - Scaling and memory in volatility return intervals in financial markets.
AB  - For both stock and currency markets, we study the return intervals tau between
      the daily volatilities of the price changes that are above a certain threshold q.
      We find that the distribution function Pq(tau) scales with the mean return
      interval tau as Pq(tau)=tau(-1)f(tau/tau). The scaling function fx is similar in
      form for all seven stocks and for all seven currency databases analyzed, and fx
      is consistent with a power-law form, fx approximately x(-gamma) with gamma
      approximately 2. We also quantify how the conditional distribution Pq(tau/tau0)
      depends on the previous return interval tau0 and find that small (or large)
      return intervals are more likely to be followed by small (or large) return
      intervals. This "clustering" of the volatility return intervals is a previously
      unrecognized phenomenon that we relate to the long-term correlations known to be
      present in the volatility.

PMID- 15980150
TI  - Ras activity regulates cyclin E degradation by the Fbw7 pathway.
AB  - The Skp1-Cullin1 F-box protein-Fbw7 ubiquitin ligase regulates phosphorylation
      dependent cyclin E degradation, and disruption of this pathway is associated with
      genetic instability and tumorigenesis. Fbw7 is a human tumor suppressor that is
      targeted for mutation in primary cancers. However, mechanisms other than mutation
      of Fbw7 may also disrupt cyclin E proteolysis in cancers. We show that oncogenic
      Ha-Ras activity regulates cyclin E degradation by the Fbw7 pathway. Activated Ras
      impairs Fbw7-driven cyclin E degradation, and, conversely, inhibition of normal
      Ras activity decreases cyclin E abundance. Moreover, activation of the mitogen
      activated protein kinase pathway is the essential Ras function that inhibits
      cyclin E turnover, and activated Ha-Ras expression inhibits both the binding of
      cyclin E to Fbw7 and cyclin E ubiquitination. Last, we found that oncogenic Ras
      activity potentiates cyclin E-induced genetic instability but only when cyclin E
      is susceptible to degradation by Fbw7. Thus, we conclude that Ras activity
      regulates Fbw7-mediated cyclin E proteolysis and suggest that impaired cyclin E
      proteolysis is a mechanism through which Ras mutations promote tumorigenesis.

PMID- 15980151
TI  - Gut mucosal T cell responses and gene expression correlate with protection
      against disease in long-term HIV-1-infected nonprogressors.
AB  - Limited information is available on the molecular mechanisms by which long-term
      HIV-1-infected nonprogressors suppress HIV-1 infection and maintain immune
      functions. The intestinal mucosal immune system is an early target for HIV-1
      infection and severe CD4+ T cell depletion. We evaluated mucosal T lymphocyte
      subsets, virus-specific cellular responses, gene expression profiles, and viral
      loads in intestinal mucosal biopsies of long-term nonprogressor (LTNP) patients
      as compared to chronically HIV-1-infected patients with high viral loads (HVLs)
      and CD4+ T cell loss, as well as HIV-seronegative healthy individuals. This study
      aims to identify the mucosal correlates of HIV disease progression and to
      determine the molecular changes associated with immune and intestinal
      dysfunction. LTNP patients had undetectable viral loads, normal CD4+ T cell
      levels, and virus-specific cellular responses in peripheral blood and mucosal
      compartments. Microarray analysis revealed a significant increase in gene
      expression regulating immune activation, cell trafficking, and inflammatory
      response in intestinal mucosa of HVL patients as compared to LTNP patients. Genes
      associated with cell cycle regulation, lipid metabolism, and epithelial cell
      barrier and digestive functions were down-regulated in both HVL and LTNP
      patients. This may adversely influence nutrient adsorption and digestive
      functions, with the potential to impact the efficacy of antiretroviral therapy.
      We demonstrate that the maintenance of mucosal T cells, virus-specific responses,
      and distinct gene expression profiles correlate with clinical outcome in LTNP
      patients. However, the intestinal mucosal immune system remains an important
      target of HIV-1 infection in LTNP, and these effects may ultimately contribute
      toward disease progression.

PMID- 15980153
TI  - Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA
      in control of the NFAT signaling pathway in gastric epithelial cells.
AB  - Chronic infection with cagA-positive Helicobacter pylori is associated with the
      development of atrophic gastritis, peptic ulcers, and gastric adenocarcinoma. The
      cagA gene product CagA is injected into gastric epithelial cells, where it
      undergoes tyrosine phosphorylation by Src family kinases. Translocated CagA
      disturbs cellular functions by physically interacting with and deregulating
      intracellular signaling transducers through both tyrosine phosphorylation
      dependent and -independent mechanisms. To gain further insights into the
      pathophysiological activities of CagA in gastric epithelial cells, we executed a
      genome-wide screening of CagA-responsive genes by using DNA microarray and
      identified nuclear factor of activated T cells (NFAT) transcription factors whose
      binding sites were overrepresented in the promoter regions of CagA-activated
      genes. Results of reporter assays confirmed that CagA was capable of activating
      NFAT in a manner independent of CagA phosphorylation. Expression of CagA in
      gastric epithelial cells provoked translocation of NFATc3, a member of the NFAT
      family, from the cytoplasm to the nucleus and activated an NFAT-regulated gene,
      p21WAF1/Cip1. CagA-mediated NFAT activation was abolished by inhibiting
      calcineurin or phospholipase Cgamma activity. Furthermore, treatment of cells
      with H. pylori VacA (vacuolating toxin), which inhibits NFAT activity in T
      lymphocytes, counteracted the ability of CagA to activate NFAT in gastric
      epithelial cells. These findings indicate that the two major H. pylori virulence
      factors inversely control NFAT activity. Considering the pleiotropic roles of
      NFAT in cell growth and differentiation, deregulation of NFAT, either positively
      or negatively, depending on the relative exposure of cells to CagA and VacA, may
      contribute to the various disease outcomes caused by H. pylori infection.

PMID- 15980154
TI  - Drug resistance in cancer: principles of emergence and prevention.
AB  - Although targeted therapy is yielding promising results in the treatment of
      specific cancers, drug resistance poses a problem. We develop a mathematical
      framework that can be used to study the principles underlying the emergence and
      prevention of resistance in cancers treated with targeted small-molecule drugs.
      We consider a stochastic dynamical system based on measurable parameters, such as
      the turnover rate of tumor cells and the rate at which resistant mutants are
      generated. We find that resistance arises mainly before the start of treatment
      and, for cancers with high turnover rates, combination therapy is less likely to
      yield an advantage over single-drug therapy. We apply the mathematical framework
      to chronic myeloid leukemia. Early-stage chronic myeloid leukemia was the first
      case to be treated successfully with a targeted drug, imatinib (Novartis, Basel).
      This drug specifically inhibits the BCR-ABL oncogene, which is required for
      progression. Although drug resistance prevents successful treatment at later
      stages of the disease, our calculations suggest that, within the model
      assumptions, a combination of three targeted drugs with different specificities
      might overcome the problem of resistance.

PMID- 15980156
TI  - Can a GDP-liganded G-protein be active?
AB  - The replacement of GDP bound to the alpha-subunit of a G-protein by GTP is
      generally considered a crucial step in the activation of effectors by a G
      protein. New data by Ugur et al. (2005) (p. 720) raise the possibility that for
      the heterotrimeric G-protein Gs, GDP-liganded Gs is able to activate the effector
      adenylyl cyclase as potently and effectively as when Gs is in its GTP bound form.
      We summarize here the evidence that GTP is necessary for effector activation by G
      proteins and discuss potential implications and limitations of data to the
      contrary.

PMID- 15980155
TI  - The application of statistical physics to evolutionary biology.
AB  - A number of fundamental mathematical models of the evolutionary process exhibit
      dynamics that can be difficult to understand analytically. Here we show that a
      precise mathematical analogy can be drawn between certain evolutionary and
      thermodynamic systems, allowing application of the powerful machinery of
      statistical physics to analysis of a family of evolutionary models. Analytical
      results that follow directly from this approach include the steady-state
      distribution of fixed genotypes and the load in finite populations. The analogy
      with statistical physics also reveals that, contrary to a basic tenet of the
      nearly neutral theory of molecular evolution, the frequencies of adaptive and
      deleterious substitutions at steady state are equal. Finally, just as the free
      energy function quantitatively characterizes the balance between energy and
      entropy, a free fitness function provides an analytical expression for the
      balance between natural selection and stochastic drift.

PMID- 15980157
TI  - Novel targeted therapies in the treatment of gastric and esophageal cancer.
AB  - Esophageal cancer (EC) and gastric cancer (GC) constitute a major cause of cancer
      deaths worldwide. Recent improvements in both surgical techniques and
      adjuvant/neoadjuvant radiotherapy and chemotherapy approaches have increased the
      survival of patients with loco-regional disease. However, most of the patients
      with GC or EC have advanced disease either at diagnosis or at follow-up. Despite
      recent advances in the treatment of advanced disease, these patients still do
      poorly. An emerging understanding of the molecular pathways that characterize
      cell growth, cell cycle, apoptosis, angiogenesis and invasion has provided novel
      targets in cancer therapy. In this review we describe the current status of
      targeted therapies in the treatment of EC and GC. These therapeutic strategies
      include EGFR inhibitors, antiangiogenic agents, cell cycle inhibitors, apoptosis
      promoters and matrix metalloproteinases inhibitors. The emerging data from the
      clinical development of these compounds has provided novel opportunities in the
      treatment of EC and GC that will probably translate into efficacy advantage in
      the treatment of these common malignancies.

PMID- 15980159
TI  - Should women be advised to take prophylactic endocrine treatment outside of a
      clinical trial setting?
AB  - Epidemiological, experimental and clinical data strongly support the possibility
      that breast cancer can be prevented by using anti-estrogenic interventions in
      healthy women. Four trials involving over 25,000 women have so far been reported
      using tamoxifen 20 mg/day or placebo in healthy women to chemoprevent breast
      cancer, and several trials utilizing raloxifene or aromatase inhibitors are
      underway. Interim analyses of the Royal Marsden tamoxifen trial and the Italian
      national trial showed no effect on the early incidence of breast cancer. The
      NSABP-P1 showed a 49% reduction in early incidence of breast cancer. This was
      associated with a reduction in osteoporotic fractures but increases in the risks
      of endometrial cancer, cataract and thromboembolism. The IBIS trial showed a 32%
      reduction with a two-fold increase in endometrial cancer and in thromboembolic
      events. Mortality rates of breast cancer in women receiving tamoxifen
      prophylactically should be monitored and further follow-up of these trials is
      needed to determine whether tamoxifen provides an overall health benefit or
      increase specific or overall survival of breast cancer. High-risk women should
      not be advised to take anti-estrogens outside of a clinical trial setting.

PMID- 15980158
TI  - Proliferative markers as prognostic and predictive tools in early breast cancer:
      where are we now?
AB  - In the last few decades, proliferative markers have been broadly evaluated as
      prognostic and predictive factors for early stage breast cancer patients. Several
      papers evaluating one or more markers have been published, often with
      contradictory results. As a consequence, there is still uncertainty about the
      role of these proliferative markers. The present paper critically reviews the
      current knowledge about the following markers: thymidine labeling index, S phase
      fraction/flow cytometry, Ki 67, thymidine kinase (TK), cyclins E, cyclin D, the
      cyclin inhibitors p27 and p21, and topoisomerase IIalpha. For each marker, the
      prognostic and predictive role was separately analyzed. Only papers published in
      English in peer-reviewed journals before June 2004 that include at least 100
      evaluable patients were selected. In addition, the prognostic and predictive role
      of the proliferative markers had to be assessed through multivariate analyses.
      One hundred and thirty-two papers fulfilled these criteria and 159 516 patients
      were analyzed. Unfortunately, several methodological problems in the research to
      date prevent us from including any one of these proliferative markers among the
      standard prognostic and predictive factors. Early incorporation of translational
      research and new technologies with clinical trials are needed to prospectively
      validate biological markers and allow their use in clinical practice.

PMID- 15980160
TI  - Epidermal growth factor receptor (EGFR) status in primary colorectal tumors
      correlates with EGFR expression in related metastatic sites: biological and
      clinical implications.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) plays an important role in
      the pathogenesis of colorectal cancer (CRC). There are several potential
      strategies to target EGFR. However, monoclonal antibodies and low molecular
      weight tyrosine kinase inhibitors are the most advanced in clinical development.
      The majority of studies so far have merely required EGFRs to be expressed by CRC
      cells. The detection of EGFR expression is usually performed by
      immunohistochemistry (IHC) in the primary tumor. There are few data regarding the
      EGFR status in the corresponding distant metastases. PATIENTS AND METHODS: EGFR
      status was analyzed by IHC in 80 patients (31 male, 49 female) with CRC (70
      colon, 10 rectum) and at least one distant metastatic lesion. Metastatic sites
      analyzed (n=80) were liver (79 patients) and lung (one patient). RESULTS: EGFR
      reactivity was similar in the primary tumor and the related metastases. Among the
      80 paired primary/metastatic tumors, only five (6.3%) showed discordance in EGFR
      status: two cases with EGFR expression in the primary tumor but not in the
      metastasis, and three samples with EGFR expression in the metastasis but not in
      the primary tumor. CONCLUSIONS: Between the paired primary tumors and distant
      metastatic lesions, 94% of samples had concordant EGFR status when analyzed by
      IHC.

PMID- 15980161
TI  - FDG-PET after two to three cycles of chemotherapy predicts progression-free and
      overall survival in high-grade non-Hodgkin lymphoma.
AB  - BACKGROUND: Less than 50% of all high-grade non-Hodgkin lymphoma (NHL) patients
      experience lasting disease-free survival. Risk-adapted treatment strategies
      require better tools for prediction of outcome. This investigation aimed to
      assess the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D
      glucose (FDG-PET) after two to three cycles of chemotherapy for prediction of
      progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS:
      One hundred and twenty-one patients with high-grade NHL underwent FDG-PET. The
      therapy response on FDG-PET was correlated to PFS and OS using Kaplan-Meier
      survival analysis. Cox regression analyses were employed to test for independence
      of known pretreatment prognostic factors. RESULTS: Fifty FDG-PET scans were
      negative, 19 scans showed minimal residual uptake (MRU), and 52 scans were
      positive. The estimated 5 year PFS was 88.8% for the PET-negative group, 59.3%
      for the MRU group, and 16.2% for the PET-positive group. Kaplan-Meier analyses
      showed strong associations between FDG-PET results and PFS (P <0.0001) and OS (P
      <0.01). Early interim FDG-PET was independent of the other prognostic factors.
      CONCLUSIONS: Early interim FDG-PET is an accurate and independent predictor of
      PFS and OS. An early assessment of chemotherapy response with FDG-PET could
      provide the basis for selection of patients for alternative therapeutic
      strategies.

PMID- 15980162
TI  - Modeling analytical ultracentrifugation experiments with an adaptive space-time
      finite element solution of the Lamm equation.
AB  - Analytical ultracentrifugation experiments can be accurately modeled with the
      Lamm equation to obtain sedimentation and diffusion coefficients of the solute.
      Existing finite element methods for such models can cause artifactual
      oscillations in the solution close to the endpoints of the concentration
      gradient, or fail altogether, especially for cases where somega(2)/D is large.
      Such failures can currently only be overcome by an increase in the density of the
      grid points throughout the solution at the expense of increased computational
      costs. In this article, we present a robust, highly accurate and computationally
      efficient solution of the Lamm equation based on an adaptive space-time finite
      element method (ASTFEM). Compared to the widely used finite element method by
      Claverie and the moving hat method by Schuck, our ASTFEM method is not only more
      accurate but also free from the oscillation around the cell bottom for any
      somega(2)/D without any increase in computational effort. This method is
      especially superior for cases where large molecules are sedimented at faster
      rotor speeds, during which sedimentation resolution is highest. We describe the
      derivation and grid generation for the ASTFEM method, and present a quantitative
      comparison between this method and the existing solutions.

PMID- 15980163
TI  - A model for intracellular trafficking of adenoviral vectors.
AB  - Here we develop an integrative computational framework to model biophysical
      processes involved in viral gene delivery. The model combines reaction-diffusion
      advection equations that describe intracellular trafficking with kinetic
      equations that describe transcription and translation of the exogenous DNA. It
      relates molecular-level trafficking events to whole-cell distribution of viruses.
      The approach makes use of the current understanding of cellular processes and
      data from single-particle single-cell imaging experiments. The model reveals two
      important parameters that characterize viral transport at the population level,
      namely, the effective velocity, V(eff), and the effective diffusion coefficient,
      D(eff). V(eff) measures virus's net movement rate and D(eff) represents the total
      dispersion rate. We employ the model to study the influence of microtubule
      mediated movements on nuclear targeting and gene expression of adenoviruses of
      type 2 and type 5 in HeLa and A549 cells. Effects of microtubule organization and
      the presence of microtubule-destabilizing drugs on viral transport were analyzed
      and quantified. Model predictions agree well with experimental data available in
      literature. The paper serves as a guide for future theoretical and experimental
      efforts to understand viral gene delivery.

PMID- 15980164
TI  - Amino acid substitutions in the pore of the Ca(V)1.2 calcium channel reduce
      barium currents without affecting calcium currents.
AB  - Ba(2+) currents through Ca(V)1.2 Ca(2+) channels are typically twice as large as
      Ca(2+) currents. Replacing Phe-1144 in the pore-loop of domain III with glycine
      and lysine, and Tyr-1152 with lysine, reduces whole-cell G(Ba)/G(Ca) from 2.2
      (wild-type) to 0.95, 1.21, and 0.90, respectively. Whole-cell and single-channel
      measurements indicate that reductions in G(Ba)/G(Ca) result specifically from a
      decrease in Ba(2+) conductance and not changes in V(h) or P(O). Half-maximal
      block of I(Li) is increased by 3.2-, 3.8-, and 1.6-fold in Ca(2+), and 3.8-, 4.2
      , and 1.8-fold in Ba(2+) for F1144G, Y1152K, and F1144K, respectively. High
      affinity interactions of individual divalent cations to the pore are not
      important for determining G(Ba)/G(Ca), because the fold increases in IC(50)
      values for Ba(2+) and Ca(2+) are similar. On the contrary, conductance
      concentration curves indicate that G(Ba)/G(Ca) is reduced because the
      interactions of multiple Ba(2+) ions in the mutant pores are altered. The
      complexity of these interactions is exemplified by the anomalous mole fraction
      effect, which is flattened for F1144G and FY/GK but accentuated for F1144K. In
      summary, the physicochemical properties of the amino acid residues at positions
      1144 and 1152 are crucial to the pore's ability to distinguish between multiple
      Ba(2+) ions and Ca(2+) ions.

PMID- 15980165
TI  - Behavior of Tn3 resolvase in solution and its interaction with res.
AB  - The solution properties of Tn3 resolvase (Tn3R) were studied by sedimentation
      equilibrium, sedimentation velocity analytical ultracentrifugation, and small
      angle neutron scattering. Tn3R was found to be in a monomer-dimer self
      association equilibrium, with a dissociation constant of K(D)(1-2)=50 microM.
      Sedimentation velocity and small-angle neutron scattering data are consistent
      with a solution structure of dimeric Tn3R similar to that of gammadelta resolvase
      in a co-crystal structure, but with the DNA-binding domains in a more extended
      conformation. The solution conformations of sites I, II, and III were studied
      with small angle x-ray scattering and modeled using rigid-body and ab initio
      techniques. The structures of these sites do not show any distortion, at low
      resolution, from B-DNA. The equilibrium binding properties of Tn3R to the
      individual binding sites in res were investigated by employing fluorescence
      anisotropy measurements. It was found that site II and site III have the highest
      affinity for Tn3R, followed by site I. Finally, the affinity of Tn3R for
      nonspecific DNA was assayed by competition experiments.

PMID- 15980166
TI  - Direct measurement of osmotic pressure of glycosaminoglycan solutions by membrane
      osmometry at room temperature.
AB  - Articular cartilage is a hydrated soft tissue composed of negatively charged
      proteoglycans fixed within a collagen matrix. This charge gradient causes the
      tissue to imbibe water and swell, creating a net osmotic pressure that enhances
      the tissue's ability to bear load. In this study we designed and utilized an
      apparatus for directly measuring the osmotic pressure of chondroitin sulfate, the
      primary glycosaminoglycan found in articular cartilage, in solution with varying
      bathing ionic strength (0.015 M, 0.15 M, 0.5 M, 1 M, and 2 M NaCl) at room
      temperature. The osmotic pressure (pi) was found to increase nonlinearly with
      increasing chondroitin sulfate concentration and decreasing NaCl ionic bath
      environment. Above 1 M NaCl, pi changes negligibly with further increases in salt
      concentration, suggesting that Donnan osmotic pressure is negligible above this
      threshold, and the resulting pressure is attributed to configurational entropy.
      Results of the current study were also used to estimate the contribution of
      osmotic pressure to the stiffness of cartilage based on theoretical and
      experimental considerations. Our findings indicate that the osmotic pressure
      resulting from configurational entropy is much smaller in cartilage (based on an
      earlier study on bovine articular cartilage) than in free solution. The rate of
      change of osmotic pressure with compressive strain is found to contribute
      approximately one-third of the compressive modulus (H(A)(eff)) of cartilage (Pi
      approximately H(A)(eff)/3), with the balance contributed by the intrinsic
      structural modulus of the solid matrix (i.e., H(A) approximately 2H(A)(eff)/3). A
      strong dependence of this intrinsic modulus on salt concentration was found;
      therefore, it appears that proteoglycans contribute structurally to the magnitude
      of H(A), in a manner independent of osmotic pressure.

PMID- 15980167
TI  - Hydrogen bonding dynamics during protein folding of reduced cytochrome c:
      temperature and denaturant concentration dependence.
AB  - Folding dynamics of reduced cytochrome c triggered by the laser-induced reduction
      method is investigated from a viewpoint of the intermolecular interaction change.
      Change of the diffusion coefficient of cytochrome c during the refolding process
      is traced in the time domain from the unfolded value to the native value
      continuously at various denaturant (guanidine hydrochloride (GdnHCl))
      concentrations and temperatures. In the temperature range of 288 K-308 K and
      GdnHCl concentration range of 2.5 M-4.25 M, the diffusion change can be analyzed
      well by the two-state model consistently. It was found that the m(double dagger)
      value and the activation energy of the transition state from the unfolded state
      for the hydrogen bonding network change are surprisingly similar to that for the
      local structural change around the heme group monitored by the fluorescence
      quenching experiment. This agreement suggests the existence of common or similar
      fundamental dynamics including water molecular movement to control the refolding
      dynamics. The nature of the transition state is discussed.

PMID- 15980168
TI  - Carboxy-terminal truncations modify the outer pore vestibule of muscle chloride
      channels.
AB  - Mammalian ClC-type chloride channels have large cytoplasmic carboxy-terminal
      domains whose function is still insufficiently understood. We investigated the
      role of the distal part of the carboxy-terminus of the muscle isoform ClC-1 by
      constructing and functionally evaluating two truncation mutants, R894X and K875X.
      Truncated channels exhibit normal unitary conductances and anion selectivities
      but altered apparent anion binding affinities in the open and in the closed
      state. Since voltage-dependent gating is strictly coupled to ion permeation in
      ClC-1 channels, the changed pore properties result in different fast and slow
      gating. Full length and truncated channels also differed in methanethiosulphonate
      (MTS) modification rate constants of an engineered cysteine at position 231 near
      the selectivity filter. Our data demonstrate that the carboxy-terminus of ClC
      channels modifies the conformation of the outer pore vestibule.

PMID- 15980169
TI  - Effects of urea and trimethylamine-N-oxide (TMAO) on the interactions of lysozyme
      in solution.
AB  - The effect of two physiological cosolutes (urea and trimethylamine-N-oxide) and
      of KCl on the intermolecular interactions in concentrated lysozyme solutions were
      studied by synchrotron radiation small angle x-ray scattering. The evolution of
      the structure factors as a function of cosolute and/or salt concentration was
      modeled using pair potentials following an approach recently described in the
      literature. It was found that the structure factors for salt and/or cosolute
      concentration series at a fixed protein concentration can best be described using
      a variable depth attractive potential and a constant effective charge rather than
      a constant attractive potential and a variable effective charge as done in
      previous work.

PMID- 15980170
TI  - Molecular dynamics simulations reveal multiple pathways of ligand dissociation
      from thyroid hormone receptors.
AB  - Nuclear receptor (NR) ligands occupy a pocket that lies within the core of the NR
      ligand-binding domain (LBD), and most NR LBDs lack obvious entry/exit routes upon
      the protein surface. Thus, significant NR conformational rearrangements must
      accompany ligand binding and release. The precise nature of these processes,
      however, remains poorly understood. Here, we utilize locally enhanced sampling
      (LES) molecular dynamics computer simulations to predict molecular motions of x
      ray structures of thyroid hormone receptor (TR) LBDs and determine events that
      permit ligand escape. We find that the natural ligand 3,5,3'-triiodo-L-thyronine
      (T(3)) dissociates from the TRalpha1 LBD along three competing pathways generated
      through i), opening of helix (H) 12; ii), separation of H8 and H11 and the Omega
      loop between H2 and H3; and iii), opening of H2 and H3, and the intervening beta
      strand. Similar pathways are involved in dissociation of T(3) and the TRbeta
      selective ligand GC24 from TRbeta; the TR agonist IH5 from the alpha- and beta-TR
      forms; and Triac from two natural human TRbeta mutants, A317T and A234T, but are
      detected with different frequencies in simulations performed with the different
      structures. Path I was previously suggested to represent a major pathway for NR
      ligand dissociation. We propose here that Paths II and III are also likely ligand
      escape routes for TRs and other NRs. We also propose that different escape paths
      are preferred in different situations, implying that it will be possible to
      design NR ligands that only associate stably with their cognate receptors in
      specific cellular contexts.

PMID- 15980171
TI  - Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2
      channels.
AB  - This work demonstrates cell swelling as a new regulatory mechanism for the cloned
      hyperpolarization-activated, cyclic nucleotide-gated channel 2 (HCN2). HCN2
      channels were coexpressed with aquaporin1 in Xenopus laevis oocytes and currents
      were monitored using a two-electrode voltage-clamp. HCN2 channels were activated
      by hyperpolarization to -100 mV and the currents were measured before and during
      hypoosmotic cell swelling. Cell swelling increased HCN2 currents by 30% without
      changing the kinetics of the currents. Injection of 50 nl intracellular solution
      resulted in a current increase of 20%, indicating that an increase in cell volume
      also under isoosmotic conditions may lead to activation of HCN2. In the absence
      of aquaporin1 only negligible changes in oocyte cell volume occur during exposure
      to hypoosmotic media and no significant change in HCN2 channel activity was
      observed during perfusion with hypoosmotic media. This indicates that cell
      swelling and not a change in ionic strength of the media, caused the observed
      swelling-induced increase in current. The increase in HCN2 current induced by
      cell swelling could be abolished by cytochalasin D treatment, indicating that an
      intact F-actin cytoskeleton is a prerequisite for the swelling-induced current.

PMID- 15980172
TI  - The approach to the Michaelis complex in lactate dehydrogenase: the substrate
      binding pathway.
AB  - We examine here the dynamics of forming the Michaelis complex of the enzyme
      lactate dehydrogenase by characterizing the binding kinetics and thermodynamics
      of oxamate (a substrate mimic) to the binary lactate dehydrogenase/NADH complex
      over multiple timescales, from nanoseconds to tens of milliseconds. To access
      such a wide time range, we employ standard stopped-flow kinetic approaches
      (slower than 1 ms) and laser-induced temperature-jump relaxation spectroscopy (10
      ns-10 ms). The emission from the nicotinamide ring of NADH is used as a marker of
      structural transformations. The results are well explained by a kinetic model
      that has binding taking place via a sequence of steps: the formation of an
      encounter complex in a bimolecular step followed by two unimolecular
      transformations on the microsecond/millisecond timescales. All steps are well
      described by single exponential kinetics. It appears that the various key
      components of the catalytically competent architecture are brought together as
      separate events, with the formation of strong hydrogen bonding between active
      site His(195) and substrate early in binding and the closure of the catalytically
      necessary protein surface loop over the bound substrate as the final event of the
      binding process. This loop remains closed during the entire period that chemistry
      takes place for native substrates; however, motions of other key molecular groups
      bringing the complex in and out of catalytic competence appear to occur on faster
      timescales. The on-enzyme K(d) values (the ratios of the microscopic rate
      constants for each unimolecular step) are not far from one. Either substantial,
      approximately 10-15%, transient melting of the protein or rearrangements of
      hydrogen bonding and solvent interactions of a number of water molecules or both
      appear to take place to permit substrate access to the protein binding site. The
      nature of activating the various steps in the binding process seems to be one
      overall involving substantial entropic changes.

PMID- 15980173
TI  - Effect of packing density on rhodopsin stability and function in polyunsaturated
      membranes.
AB  - Rod outer segment disk membranes are densely packed with rhodopsin. The recent
      notion of raft or microdomain structures in disk membranes suggests that the
      local density of rhodopsin in disk membranes could be much higher than the
      average density corresponding to the lipid/protein ratio. Little is known about
      the effect of high packing density of rhodopsin on the structure and function of
      rhodopsin and lipid membranes. Here we examined the role of rhodopsin packing
      density on membrane dynamic properties, membrane acyl chain packing, and the
      structural stability and function of rhodopsin using a combination of biophysical
      and biochemical techniques. We reconstituted rhodopsin into large unilamellar
      vesicles consisting of polyunsaturated 18:0,22:6n3PC, which approximates the
      polyunsaturated nature of phospholipids in disk membranes, with rhodopsin/lipid
      ratios ranging from 1:422 to 1:40. Our results showed that increased rhodopsin
      packing density led to reduced membrane dynamics revealed by the fluorescent
      probe 1,6-diphenyl-1,3,5-hexatriene, increased phospholipid acyl chain packing,
      and reduced rhodopsin activation, yet it had minimal impact on the structural
      stability of rhodopsin. These observations imply that densely packed rhodopsin
      may impede the diffusion and conformational changes of rhodopsin, which could
      reduce the speed of visual transduction.

PMID- 15980174
TI  - CD8 kinetically promotes ligand binding to the T-cell antigen receptor.
AB  - The mechanism of CD8 cooperation with the TCR in antigen recognition was studied
      on live T cells. Fluorescence correlation measurements yielded evidence of the
      presence of two TCR and CD8 subpopulations with different lateral diffusion rate
      constants. Independently, evidence for two subpopulations was derived from the
      experimentally observed two distinct association phases of cognate peptide bound
      to class I MHC (pMHC) tetramers and the T cells. The fast phase rate constant
      ((1.7 +/- 0.2) x 10(5) M(-1) s(-1)) was independent of examined cell type or MHC
      bound peptides' structure. Its value was much faster than that of the association
      of soluble pMHC and TCR ((7.0 +/- 0.3) x 10(3) M(-1) s(-1)), and close to that of
      the association of soluble pMHC with CD8 ((1-2) x 10(5) M(-1) s(-1)). The fast
      binding phase disappeared when CD8-pMHC interaction was blocked by a CD8-specific
      mAb. The latter rate constant was slowed down approximately 10-fold after cells
      treatment with methyl-beta-cyclodextrin. These results suggest that the most
      efficient pMHC-cell association route corresponds to a fast tetramer binding to a
      colocalized CD8-TCR subpopulation, which apparently resides within membrane
      rafts: the reaction starts by pMHC association with the CD8. This markedly faster
      step significantly increases the probability of pMHC-TCR encounters and thereby
      promotes pMHC association with CD8-proximal TCR. The slow binding phase is
      assigned to pMHC association with a noncolocalized CD8-TCR subpopulation. Taken
      together with results of cytotoxicity assays, our data suggest that the
      colocalized, raft-associated CD8-TCR subpopulation is the one capable of inducing
      T-cell activation.

PMID- 15980175
TI  - Visualization of synaptic vesicle movement in intact synaptic boutons using
      fluorescence fluctuation spectroscopy.
AB  - Not much is known about the mobility of synaptic vesicles inside small synapses
      of the central nervous system, reflecting a lack of methods for visualizing these
      dynamics. We adapted confocal spot detection with fluctuation analysis to monitor
      the mobility of fluorescently labeled synaptic vesicles inside individual boutons
      of cultured hippocampal neurons. Using Monte Carlo simulations we were able to
      propose a simple quantitative model that can describe vesicle mobility in small
      hippocampal boutons under resting conditions and different pharmacological
      treatments. We find that vesicle mobility in a time window of 20 s can be well
      described by caged diffusion (D approximately 5 x 10(-5) microm(2)/s, cage sizes
      of approximately 50 nm). Mobility can be upregulated by phosphatase blockage and
      increased further by actin disruption in a dose-dependent manner. Inhibition of
      the myosin light chain kinase slows down vesicle mobility 10-fold, whereas other
      kinases like protein kinase C (PKC), A (PKA), and calmodulin kinase II (caMKII)
      do not affect mobility in unstimulated boutons.

PMID- 15980177
TI  - The nature of the gecko lizard adhesive force.
AB  - The extraordinary climbing skills of gecko lizards have been under investigation
      for a long time. Here we report results of direct measurement of single spatula
      forces in air with varying relative humidities and in water, by the force
      distance method using an atomic force microscope. We have found that the presence
      of water strongly affects the adhesion force and from analysis of our results, we
      have demonstrated that the dominant force involved is the capillary force.

PMID- 15980176
TI  - Bacterial shape and ActA distribution affect initiation of Listeria monocytogenes
      actin-based motility.
AB  - We have examined the process by which the intracellular bacterial pathogen
      Listeria monocytogenes initiates actin-based motility and determined the
      contribution of the variable surface distribution of the ActA protein to
      initiation and steady-state movement. To directly correlate ActA distributions to
      actin dynamics and motility of live bacteria, ActA was fused to a monomeric red
      fluorescent protein (mRFP1). Actin comet tail formation and steady-state
      bacterial movement rates both depended on ActA distribution, which in turn was
      tightly coupled to the bacterial cell cycle. Motility initiation was found to be
      a highly complex, multistep process for bacteria, in contrast to the simple
      symmetry breaking previously observed for ActA-coated spherical beads. F-actin
      initially accumulated along the sides of the bacterium and then slowly migrated
      to the bacterial pole expressing the highest density of ActA as a tail formed.
      Early movement was highly unstable with extreme changes in speed and frequent
      stops. Over time, saltatory motility and sensitivity to the immediate environment
      decreased as bacterial movement became robust at a constant steady-state speed.

PMID- 15980178
TI  - Incomplete ion dissociation underlies the weakened attraction between DNA helices
      at high spermidine concentrations.
AB  - We have investigated the salt sensitivity of the hexagonal-to-cholesteric phase
      transition of spermidine-condensed DNA. This transition precedes the
      resolubilization of precipitated DNA that occurs at high spermidine
      concentration. The sensitivity of the critical spermidine concentration at the
      transition point to the anion species and the NaCl concentration indicates that
      ion pairing of this trivalent ion underlies this unusual transition. Osmotic
      pressure measurements of spermidine salt solutions are consistent with this
      interpretation. Spermidine salts are not fully dissociated at higher
      concentrations. The competition for DNA binding among the fully charged trivalent
      ion and the lesser charged complex species at higher concentrations significantly
      weakens attraction between DNA helices in the condensed state. This is contrary
      to the suggestion that the binding of spermidine at higher concentrations causes
      DNA overcharging and consequent electrostatic repulsion.

PMID- 15980179
TI  - Caveolin-3 is adjacent to a group of extradyadic ryanodine receptors.
AB  - Caveolae are present in almost all cells and concentrate a wide variety of
      signaling molecules, receptors, transporters, and ion pumps. We have investigated
      the distribution of the ryanodine receptor, the Na(+)/Ca(2+) exchanger, the
      predominant Na(+) channel isoform rH1, and the L-type calcium channel, Ca(v)1.2,
      relative to the muscle-specific caveolin isoform, caveolin-3, in adult rat
      ventricular myocytes. Three-dimensional immunofluorescence images were
      deconvolved and analyzed. Caveolin-3 colocalizes with all of these molecules at
      the surface of the cell, but there is no significant colocalization between
      caveolin-3 and either the Na(+)/Ca(2+) exchanger or the Na(+) channel in the cell
      interior. The distribution of the surface colocalization indicates that the
      caveolae that colocalize with each molecule form distinct populations. This
      organization indicates that there are multiple populations of caveolae separable
      by location and occupants. In the interior of the cell, caveolin-3 shows a marked
      colocalization with a population of ryanodine receptors that are separate from
      those within the dyad. Because of their location, the signaling molecules
      contained within these caveolae may have preferred access to the neighboring
      nondyadic ryanodine receptors.

PMID- 15980180
TI  - Effect of ion-binding and chemical phospholipid structure on the nanomechanics of
      lipid bilayers studied by force spectroscopy.
AB  - The nanomechanical response of supported lipid bilayers has been studied by force
      spectroscopy with atomic force microscopy. We have experimentally proved that the
      amount of ions present in the measuring system has a strong effect on the force
      needed to puncture a 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer with an
      atomic force microscope tip, thus highlighting the role that monovalent cations
      (so far underestimated, e.g., Na(+)) play upon membrane stability. The increase
      in the yield threshold force has been related to the increase in lateral
      interactions (higher phospholipid-phospholipid interaction, decrease in area per
      lipid) promoted by ions bound into the membrane. The same tendency has also been
      observed for other phosphatidylcholine bilayers, namely, 2-dilauroyl-sn-glycero-3
      phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1,2-dioleoyl-sn
      3-phosphocholine, and also for phosphatidylethanolamine bilayers such as 1
      palmitoyl-2-oleoyl-sn-3-phosphoethanolamine. Finally, this effect has been also
      tested on a natural lipid bilayer (Escherichia coli lipid extract), showing the
      same overall tendency. The kinetics of the process has also been studied,
      together with the role of water upon membrane stability and its effect on
      membrane nanomechanics. Finally, the effect of the chemical structure of the
      phospholipid molecule on the nanomechanical response of the membrane has also
      been discussed.

PMID- 15980181
TI  - Pressure perturbation and differential scanning calorimetric studies of bipolar
      tetraether liposomes derived from the thermoacidophilic archaeon Sulfolobus
      acidocaldarius.
AB  - Differential scanning calorimetry (DSC) and pressure perturbation calorimetry
      (PPC) were used to characterize thermal phase transitions, membrane packing, and
      volumetric properties in multilamellar vesicles (MLVs) composed of the polar
      lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon Sulfolobus
      acidocaldarius grown at different temperatures. For PLFE MLVs derived from cells
      grown at 78 degrees C, the first DSC heating scan exhibits an endothermic
      transition at 46.7 degrees C, a small hump near 60 degrees C, and a broad
      exothermic transition at 78.5 degrees C, whereas the PPC scan reveals two
      transitions at approximately 45 degrees C and 60 degrees C. The endothermic peak
      at 46.7 degrees C is attributed to a lamellar-to-lamellar phase transition and
      has an unusually low DeltaH (3.5 kJ/mol) and DeltaV/V (0.1%) value, as compared
      to those for the main phase transitions of saturated diacyl monopolar diester
      lipids. This result may arise from the restricted trans-gauche conformational
      changes in the dibiphytanyl chain due to the presence of cyclopentane rings and
      branched methyl groups and due to the spanning of the lipid molecules over the
      whole membrane. The exothermic peak at 78.5 degrees C probably corresponds to a
      lamellar-to-cubic phase transition and exhibits a large and negative DeltaH value
      (-23.2 kJ/mol), which is uncommon for normal lamellar-to-cubic phospholipid phase
      transformations. This exothermic transition disappears in the subsequent heating
      scans and thus may involve a metastable phase, which is irreversible at the scan
      rate used. Further, there is no distinct peak in the plot of the thermal
      expansion coefficient alpha versus temperature near 78.5 degrees C, indicating
      that this lamellar-to-cubic phase transition is not accompanied by any
      significant volume change. For PLFE MLVs derived from cells grown at 65 degrees
      C, similar DSC and PPC profiles and thermal history responses were obtained.
      However, the lower growth temperature yields a higher DeltaV/V ( approximately
      0.25%) and DeltaH (14 kJ/mol) value for the lamellar-to-lamellar phase transition
      measured at the same pH (2.1). A lower growth temperature also generates a less
      negative temperature dependence of alpha. The changes in DeltaV/V, DeltaH, and
      the temperature dependence of alpha can be attributed to the decrease in the
      number of cyclopentane rings in PLFE at the lower growth temperature. The
      relatively low DeltaV/V and small DeltaH involved in the phase transitions help
      to explain why PLFE liposomes are remarkably thermally stable and also echo the
      proposal that PLFE liposomes are generally rigid and tightly packed. These
      results help us to understand why, despite the occurrence of thermal-induced
      phase transitions, PLFE liposomes exhibit a remarkably low temperature
      sensitivity of proton permeation and dye leakage.

PMID- 15980182
TI  - Light-scattering studies of protein solutions: role of hydration in weak protein
      protein interactions.
AB  - We model the hydration contribution to short-range electrostatic/dispersion
      protein interactions embodied in the osmotic second virial coefficient, B(2), by
      adopting a quasi-chemical description in which water molecules associated with
      the protein are identified through explicit molecular dynamics simulations. These
      water molecules reduce the surface complementarity of highly favorable short
      range interactions, and therefore can play an important role in mediating protein
      protein interactions. Here we examine this quasi-chemical view of hydration by
      predicting the interaction part of B(2) and comparing our results with those
      derived from light-scattering measurements of B(2) for staphylococcal nuclease,
      lysozyme, and chymotrypsinogen at 25 degrees C as a function of solution pH and
      ionic strength. We find that short-range protein interactions are influenced by
      water molecules strongly associated with a relatively small fraction of the
      protein surface. However, the effect of these strongly associated water molecules
      on the surface complementarity of short-range protein interactions is
      significant, and must be taken into account for an accurate description of B(2).
      We also observe remarkably similar hydration behavior for these proteins despite
      substantial differences in their three-dimensional structures and spatial charge
      distributions, suggesting a general characterization of protein hydration.

PMID- 15980183
TI  - Pathways and timescales of primary charge separation in the photosystem II
      reaction center as revealed by a simultaneous fit of time-resolved fluorescence
      and transient absorption.
AB  - We model the dynamics of energy transfer and primary charge separation in
      isolated photosystem II (PSII) reaction centers. Different exciton models with
      specific site energies of the six core pigments and two peripheral chlorophylls
      (Chls) in combination with different charge transfer schemes have been compared
      using a simultaneous fit of the absorption, linear dichroism, circular dichroism,
      steady-state fluorescence, transient absorption upon different excitation
      wavelengths, and time-resolved fluorescence. To obtain a quantitative fit of the
      data we use the modified Redfield theory, with the experimental spectral density
      including coupling to low-frequency phonons and 48 high-frequency vibrations. The
      best fit has been obtained with a model implying that the final charge separation
      occurs via an intermediate state with charge separation within the special pair
      (RP(1)). This state is weakly dipole-allowed, due to mixing with the exciton
      states, and can be populated directly or via 100-fs energy transfer from the core
      pigments. The RP(1) and next two radical pairs with the electron transfer to the
      accessory Chl (RP(2)) and to the pheophytin (RP(3)) are characterized by
      increased electron-phonon coupling and energetic disorder. In the RP(3) state,
      the hole is delocalized within the special pair, with a predominant localization
      at the inactive-branch Chl. The intrinsic time constants of electron transfer
      between the three radical pairs vary from subpicoseconds to several picoseconds
      (depending on the realization of the disorder). The equilibration between RP(1)
      and RP(2) is reached within 5 ps at room temperature. During the 5-100-ps period
      the equilibrated core pigments and radical pairs RP(1) and RP(2) are slowly
      populated from peripheral chlorophylls and depopulated due to the formation of
      the third radical pair, RP(3). The effective time constant of the RP(3) formation
      is 7.5 ps. The calculated dynamics of the pheophytin absorption at 545 nm
      displays an instantaneous bleach (30% of the total amplitude) followed by a slow
      increase of the bleaching amplitude with time constants of 15 and 12 ps for blue
      (662 nm) and red (695 nm) excitation, respectively.

PMID- 15980184
TI  - A combined experimental and quantum chemical study on the putative protonophoric
      activity of thiocyanate.
AB  - Inhibition of gastric acid secretion by thiocyanate is explained by a
      protonophoric mechanism assuming that thiocyanate induces a H(+) back flux from
      the acidic gastric lumen into the parietal cells of gastric mucosa. Protonophoric
      activity of thiocyanate was examined by swelling measurements using rat liver
      mitochondria and theoretically by quantum chemical methods. Mitochondria
      suspended in K-thiocyanate medium plus nigericin (an H/K-exchanger) swelled when
      the medium pH was acidic, indicating that SCN(-) initiates a transfer of H(+)
      across the inner membrane. To rationalize the protonophoric activity of
      thiocyanate, we considered the dehydration of SCN(-) to be critical for
      transmembranal H(+) transfer. For modeling this process, various hydrate clusters
      of SCN(-) and Cl(-) were generated and optimized by density functional theory
      (DFT) at the B3-LYP/6-311++G(d,p) level. The cluster hydration energy was lower
      for SCN(-) than for Cl(-). The total Gibbs free energies of hydration of the ions
      were estimated by a hybrid supermolecule-continuum approach based on DFT. The
      calculated hydration energies also led to the conclusion that SCN(-) is less
      efficiently solvated than Cl(-). Due to the easier removal of the hydration shell
      of SCN(-) relative to Cl(-), SCN(-) is favored in going across the membrane,
      giving rise to the protonophoric activity.

PMID- 15980185
TI  - CORKSCREW1 defines a novel mechanism of domain specification in the maize shoot.
AB  - In higher plants, determinate leaf primordia arise in regular patterns on the
      flanks of the indeterminate shoot apical meristem (SAM). The acquisition of leaf
      form is then a gradual process, involving the specification and growth of
      distinct domains within the three leaf axes. The recessive corkscrew1 (cks1)
      mutation of maize (Zea mays) disrupts both leaf initiation patterns in the SAM
      and domain specification within the mediolateral and proximodistal leaf axes.
      Specifically, cks1 mutant leaves exhibit multiple midribs and leaf sheath tissue
      differentiates in the blade domain. Such perturbations are a common feature of
      maize mutants that ectopically accumulate KNOTTED1-like homeobox (KNOX) proteins
      in leaf tissue. Consistent with this observation, at least two knox genes are
      ectopically expressed in cks1 mutant leaves. However, ectopic KNOX proteins
      cannot be detected. We therefore propose that CKS1 primarily functions within the
      SAM to establish boundaries between meristematic and leaf zones. Loss of gene
      function disrupts boundary formation, impacts phyllotactic patterns, and leads to
      aspects of indeterminate growth within leaf primordia. Because these
      perturbations arise independently of ectopic KNOX activity, the cks1 mutation
      defines a novel component of the developmental machinery that facilitates leaf
      versus-shoot development in maize.

PMID- 15980186
TI  - Functional analysis of Arabidopsis ethylene-responsive element binding protein
      conferring resistance to Bax and abiotic stress-induced plant cell death.
AB  - Arabidopsis (Arabidopsis thaliana) ethylene-responsive element binding protein
      (AtEBP) gene was isolated as a suppressor of Bax-induced cell death by functional
      screening in yeast (Saccharomyces cerevisiae). To further examine the cell death
      suppressive action of AtEBP in plant cells, we established transgenic tobacco
      (Nicotiana tabacum) plants overexpressing AtEBP as well as transgenic tobacco
      plants ectopically expressing mouse Bax protein under a dexamethasone-inducible
      promoter. We prepared the crosses of the selective lines of each transgenic
      plant, which were evaluated in terms of cell death suppression activity. Results
      indicate that AtEBP suppressed Bax-induced cell death in tobacco plants, an
      action also associated with a lowered level of ion leakage. Furthermore, tobacco
      Bright Yellow-2 cells overexpressing AtEBP conferred resistance to hydrogen
      peroxide (H(2)O(2)) and heat treatments. AtEBP protein localized in the nucleus
      and functioned as an in vivo transcription activator as confirmed in transient
      assays and experiments using stable transgenic system. Up-regulation of defense
      genes was observed in transgenic Arabidopsis plants overexpressing AtEBP. Based
      on the analysis of mRNA accumulation in ethylene-related mutants, the position of
      AtEBP in signaling pathway is presented.

PMID- 15980187
TI  - Characterization of heterologous multigene operons in transgenic chloroplasts:
      transcription, processing, and translation.
AB  - The first characterization of transcriptional, posttranscriptional, and
      translational processes of heterologous operons expressed via the tobacco
      (Nicotiana tabacum) chloroplast genome is reported here. Northern-blot analyses
      performed on chloroplast transgenic lines harboring seven different heterologous
      operons revealed that polycistronic mRNA was the predominant transcript produced.
      Despite the lack of processing of such polycistrons, large amounts of foreign
      protein accumulation was observed in these transgenic lines, indicating abundant
      translation of polycistrons. This is supported by polysome fractionation assays,
      which allowed detection of polycistronic RNA in lower fractions of the sucrose
      gradients. These results show that the chloroplast posttranscriptional machinery
      can indeed detect and translate multigenic sequences that are not of chloroplast
      origin. In contrast to native transcripts, processed and unprocessed heterologous
      polycistrons were stable, even in the absence of 3' untranslated regions (UTRs).
      Unlike native 5'UTRs, heterologous secondary structures or 5'UTRs showed
      efficient translational enhancement independent of cellular control. Abundant
      read-through transcripts were observed in the presence of chloroplast 3'UTRs but
      they were efficiently processed at introns present within the native operon.
      Heterologous genes regulated by the psbA (the photosystem II polypeptide D1)
      promoter, 5' and 3'UTRs have greater abundance of transcripts than the endogenous
      psbA gene because transgenes were integrated into the inverted repeat region.
      Addressing questions about polycistrons, and the sequences required for their
      processing and transcript stability, are essential in chloroplast metabolic
      engineering. Knowledge of such factors would enable engineering of foreign
      pathways independent of the chloroplast complex posttranscriptional regulatory
      machinery.

PMID- 15980188
TI  - Molecular characterization of maize acetylcholinesterase: a novel enzyme family
      in the plant kingdom.
AB  - Acetylcholinesterase (AChE) has been increasingly recognized in plants by
      indirect evidence of its activity. Here, we report purification and cloning of
      AChE from maize (Zea mays), thus providing to our knowledge the first direct
      evidence of the AChE molecule in plants. AChE was identified as a mixture of
      disulfide- and noncovalently linked 88-kD homodimers consisting of 42- to 44-kD
      polypeptides. The AChE hydrolyzed acetylthiocholine and propyonylthiocholine, but
      not S-butyrylthiocholine, and the AChE-specific inhibitor neostigmine bromide
      competitively inhibited its activity, implying that maize AChE functions in a
      similar manner as the animal enzyme. However, kinetic analyses indicated that
      maize AChE showed a lower affinity to substrates and inhibitors than animal AChE.
      The full-length cDNA of maize AChE gene is 1,471 nucleotides, which encode a
      protein having 394 residues, including a signal peptide. The deduced amino acid
      sequence exhibited no apparent similarity with that of the animal enzyme,
      although the catalytic triad was the same as in the animal AChE. In silico
      screening indicated that maize AChE homologs are widely distributed in plants but
      not in animals. These findings lead us to propose that the AChE family, as found
      here, comprises a novel family of the enzymes that is specifically distributed in
      the plant kingdom.

PMID- 15980189
TI  - A gibberellin-regulated calcineurin B in rice localizes to the tonoplast and is
      implicated in vacuole function.
AB  - Many developmental and environmental signals are transduced through changes in
      intracellular calcium concentrations, yet only a few calcium-binding proteins
      have been identified in plants. Calcineurin B-like (CBL) proteins are calcium
      binding proteins that are thought to function as plant signal transduction
      elements. RNA profiling using a rice (Oryza sativa cv Nipponbare) oligonucleotide
      microarray was used to monitor gene expression in de-embryonated rice grains.
      This analysis showed that a putative rice CBL gene responded to gibberellic acid,
      but not abscisic acid, treatment. The CBL gene family in rice contains at least
      10 genes and these have extensive similarity to the CBLs of Arabidopsis
      (Arabidopsis thaliana). In yeast (Saccharomyces cerevisiae) two-hybrid assays,
      rice CBLs interact with the kinase partners of Arabidopsis CBLs. Only one rice
      CBL gene, OsCBL2, is up-regulated by GA in the aleurone layer. A homolog with 91%
      sequence identity to OsCBL2 was cloned from barley (Hordeum vulgare cv Himalaya),
      and designated HvCBL2. We examined the localization and function of OsCBL2 and
      HvCBL2 in rice and barley aleurone because changes in cytosolic calcium have been
      implicated in the response of the aleurone cell to GA. Green fluorescent protein
      translational fusions of OsCBL2 and OsCBL3 were localized to the tonoplast of
      aleurone cell protein storage vacuoles and OsCBL4-green fluorescent protein was
      localized to the plasma membrane. Data from experiments using antisense
      expression of OsCBL2 and HvCBL2 are consistent with a role for OsCBL2 in
      promoting vacuolation of barley aleurone cells following treatment with GA.

PMID- 15980190
TI  - Molecular cloning of a {beta}-galactosidase from radish that specifically
      hydrolyzes {beta}-(1->3)- and {beta}-(1->6)-galactosyl residues of
      Arabinogalactan protein.
AB  - A basic beta-galactosidase with high specificity toward beta-(1-->3)- and beta-(1
      ->6)-galactosyl residues was cloned from radish (Raphanus sativus) plants by
      reverse transcription-PCR. The gene, designated RsBGAL1, contained an open
      reading frame consisting of 2,532 bp (851 amino acids). It is expressed in
      hypocotyls and young leaves. RsBGAL1 was highly similar to beta-galactosidases
      having exo-beta-(1-->4)-galactanase activity found in higher plants and belongs
      to family 35 of the glycosyl hydrolases. Recombinant RsBGAL1 was expressed in
      Pichia pastoris and purified to homogeneity. The recombinant enzyme specifically
      hydrolyzed beta-(1-->3)- and beta-(1-->6)-galactooligosaccharides, the same
      substrates as the native enzyme isolated from radish seeds (Sekimata et al.,
      1989). It split off about 90% of the carbohydrate moieties of an arabinogalactan
      protein extracted from radish roots in concerted action with microbial alpha-l
      arabinofuranosidase and beta-glucuronidase. These results suggest that RsBGAL1 is
      a new kind of beta-galactosidase with different substrate specificity than other
      beta-galactosidases that exhibit exo-beta-(1-->4)-galactanase activity. The C
      terminal region (9.6 kD) of RsBGAL1 is significantly similar to the Gal lectin
      like domain, but this region is not retained in the native enzyme. Assuming
      posttranslational processing of RsBGAL1 with elimination of the Gal lectin-like
      domain results in a protein consisting of two subunits with molecular masses of
      46 and 34 kD (calculated from the RsBGAL1 gene sequence). This is in good
      agreement with the SDS-PAGE and matrix-assisted laser desorption/ionization-time
      of flight mass spectrometry measurements for subunits of the native enzyme (45
      and 34 kD) and may thus partially explain the formation process of the native
      enzyme.

PMID- 15980191
TI  - Flowering of the grass Lolium perenne: effects of vernalization and long days on
      gibberellin biosynthesis and signaling.
AB  - Almost 50 years ago, it was shown that gibberellin (GA) applications caused
      flowering in species normally responding to cold (vernalization) and long day
      (LD). The implication that GAs are involved with vernalization and LD responses
      is examined here with the grass Lolium perenne. This species has an obligatory
      requirement for exposure to both vernalization and LD for its flowering
      (inflorescence initiation). Specific effects of vernalization or LD on GA
      synthesis, content, and action have been documented using four treatment pairs:
      nonvernalized or vernalized plants exposed to short days (SDs) or LDs.
      Irrespective of vernalization status, exposure to two LDs increased expression of
      L. perenne GA 20-oxidase-1 (LpGA20ox1), a critical GA biosynthetic gene, with
      endogenous GAs increasing by up to 5-fold in leaf and shoot. In parallel, LD led
      to degradation of a DELLA protein, SLENDER (within 48 h of LD or within 2 h of GA
      application). There was no effect on GA catabolism or abscisic acid content. Loss
      of SLENDER, which is a repressor of GA signaling, confirms the physiological
      relevance of increased GA content in LD. For flowering, applied GA replaced the
      need for LD but not that for vernalization. Thus, GAs may be an LD, leaf-sourced
      hormonal signal for flowering of L. perenne. By contrast, vernalization had
      little impact on GA or SLENDER levels or on SLENDER degradation following GA
      application. Thus, although vernalization and GA are both required for flowering
      of L. perenne, GA signaling is independent of vernalization that apparently
      impacts on unrelated processes.

PMID- 15980192
TI  - The roothairless1 gene of maize encodes a homolog of sec3, which is involved in
      polar exocytosis.
AB  - The roothairless1 (rth1) mutant is impaired in root hair elongation and exhibits
      other growth abnormalities. Unicellular root hairs elongate via localized tip
      growth, a process mediated by polar exocytosis of secretory vesicles. We report
      here the cloning of the rth1 gene that encodes a sec3 homolog. In yeast
      (Saccharomyces cerevisiae) and mammals, sec3 is a subunit of the exocyst complex,
      which tethers exocytotic vesicles prior to their fusion. The cloning of the rth1
      gene associates the homologs of exocyst subunits to an exocytotic process in
      plant development and supports the hypothesis that exocyst-like proteins are
      involved in plant exocytosis. Proteomic analyses identified four proteins that
      accumulate to different levels in wild-type and rth1 primary roots. The
      preferential accumulation in the rth1 mutant proteome of a negative regulator of
      the cell cycle (a prohibitin) may at least partially explain the delayed
      development and flowering of the rth1 mutant.

PMID- 15980193
TI  - In vivo respiratory metabolism of illuminated leaves.
AB  - Day respiration of illuminated C(3) leaves is not well understood and
      particularly, the metabolic origin of the day respiratory CO(2) production is
      poorly known. This issue was addressed in leaves of French bean (Phaseolus
      vulgaris) using (12)C/(13)C stable isotope techniques on illuminated leaves fed
      with (13)C-enriched glucose or pyruvate. The (13)CO(2) production in light was
      measured using the deviation of the photosynthetic carbon isotope discrimination
      induced by the decarboxylation of the (13)C-enriched compounds. Using different
      positional (13)C-enrichments, it is shown that the Krebs cycle is reduced by 95%
      in the light and that the pyruvate dehydrogenase reaction is much less reduced,
      by 27% or less. Glucose molecules are scarcely metabolized to liberate CO(2) in
      the light, simply suggesting that they can rarely enter glycolysis. Nuclear
      magnetic resonance analysis confirmed this view; when leaves are fed with (13)C
      glucose, leaf sucrose and glucose represent nearly 90% of the leaf (13)C content,
      demonstrating that glucose is mainly directed to sucrose synthesis. Taken
      together, these data indicate that several metabolic down-regulations
      (glycolysis, Krebs cycle) accompany the light/dark transition and emphasize the
      decrease of the Krebs cycle decarboxylations as a metabolic basis of the light
      dependent inhibition of mitochondrial respiration.

PMID- 15980194
TI  - Water uptake and distribution in germinating tobacco seeds investigated in vivo
      by nuclear magnetic resonance imaging.
AB  - The regulation of water uptake of germinating tobacco (Nicotiana tabacum) seeds
      was studied spatially and temporally by in vivo (1)H-nuclear magnetic resonance
      (NMR) microimaging and (1)H-magic angle spinning NMR spectroscopy. These
      nondestructive state-of-the-art methods showed that water distribution in the
      water uptake phases II and III is inhomogeneous. The micropylar seed end is the
      major entry point of water. The micropylar endosperm and the radicle show the
      highest hydration. Germination of tobacco follows a distinct pattern of events:
      rupture of the testa is followed by rupture of the endosperm. Abscisic acid (ABA)
      specifically inhibits endosperm rupture and phase III water uptake, but does not
      alter the spatial and temporal pattern of phase I and II water uptake. Testa
      rupture was associated with an increase in water uptake due to initial embryo
      elongation, which was not inhibited by ABA. Overexpression of beta-1,3-glucanase
      in the seed-covering layers of transgenic tobacco seeds did not alter the
      moisture sorption isotherms or the spatial pattern of water uptake during
      imbibition, but partially reverted the ABA inhibition of phase III water uptake
      and of endosperm rupture. In vivo (13)C-magic angle spinning NMR spectroscopy
      showed that seed oil mobilization is not inhibited by ABA. ABA therefore does not
      inhibit germination by preventing oil mobilization or by decreasing the water
      holding capacity of the micropylar endosperm and the radicle. Our results support
      the proposal that different seed tissues and organs hydrate at different extents
      and that the micropylar endosperm region of tobacco acts as a water reservoir for
      the embryo.

PMID- 15980195
TI  - FesM, a membrane iron-sulfur protein, is required for cyclic electron flow around
      photosystem I and photoheterotrophic growth of the cyanobacterium Synechococcus
      sp. PCC 7002.
AB  - While it is known that cyclic electron flow around photosystem I is an important
      pathway of photosynthetic electron transfer for converting light energy to
      chemical energy, some components of cyclic electron flow remain to be revealed.
      Here, we show that fesM, encoding a novel membrane iron-sulfur protein, is
      essential to cyclic electron flow in the cyanobacterium Synechococcus sp. PCC
      7002. The FesM protein is predicted to have a cAMP-binding domain, an NtrC-like
      domain, a redox sensor motif, and an iron-sulfur (4Fe-4S) motif. Deletion of fesM
      (fesM-D) led to an inability for Synechococcus cells to grow in the presences of
      glycerol and 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Photoheterotrophic growth
      was restored by a complete fesM gene present on a replicable plasmid. A mutant
      fesM gene encoding a truncated FesM protein lacking the cAMP domain failed to
      restore the phenotype, suggesting this domain is important to the function of
      FesM. Measurements of reduction of P700(+) and the redox state of
      interphotosystem electron carriers showed that cells had a slower rate of
      respiratory electron donation to the interphotosystem electron transport chain,
      and cyclic electron flow around photosystem I in fesM-D was impaired, suggesting
      that FesM is a critical protein for respiratory and cyclic electron flow.
      Phosphatase fusion analysis showed that FesM contains nine membrane-spanning
      helices, and all functional domains of FesM are located on the cytoplasmic face
      of the thylakoid membranes.

PMID- 15980196
TI  - A Second Kazal-like protease inhibitor from Phytophthora infestans inhibits and
      interacts with the apoplastic pathogenesis-related protease P69B of tomato.
AB  - The plant apoplast forms a protease-rich environment in which proteases are
      integral components of the plant defense response. Plant pathogenic oomycetes,
      such as the potato (Solanum tuberosum) and tomato (Lycopersicon esculentum)
      pathogen Phytophthora infestans, secrete a diverse family of serine protease
      inhibitors of the Kazal family. Among these, the two-domain EPI1 protein was
      shown to inhibit and interact with the pathogenesis-related protein P69B
      subtilase of tomato and was implicated in counter-defense. Here, we describe and
      functionally characterize a second extracellular protease inhibitor, EPI10, from
      P. infestans. EPI10 contains three Kazal-like domains, one of which was predicted
      to be an efficient inhibitor of subtilisin A by an additivity-based sequence to
      reactivity algorithm (Laskowski algorithm). The epi10 gene was up-regulated
      during infection of tomato, suggesting a potential role during pathogenesis.
      Recombinant EPI10 specifically inhibited subtilisin A among the major serine
      proteases, and inhibited and interacted with P69B subtilase of tomato. The
      finding that P. infestans evolved two distinct and structurally divergent
      protease inhibitors to target the same plant protease suggests that inhibition of
      P69B could be an important infection mechanism for this pathogen.

PMID- 15980197
TI  - Dissecting defense-related and developmental transcriptional responses of maize
      during Ustilago maydis infection and subsequent tumor formation.
AB  - Infection of maize (Zea mays) plants with the smut fungus Ustilago maydis
      triggers the formation of tumors on aerial parts in which the fungal life cycle
      is completed. A differential display screen was performed to gain insight into
      transcriptional changes of the host response. Some of the genes strongly up
      regulated in tumors showed a pronounced developmental expression pattern with
      decreasing transcript levels from basal to apical shoot segments, suggesting that
      U. maydis has the capacity to extend the undifferentiated state of maize plants.
      Differentially expressed genes implicated in secondary metabolism were Bx1,
      involved in biosynthesis of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H
      1,4-benzoxazin-3-one, and a novel putative sesquiterpene cyclase gene U. maydis
      induced (Umi)2. Together with the up-regulation of Umi11 encoding a cyclotide
      like protein this suggests a nonconventional induction of plant defenses.
      Explicitly, U. maydis was resistant to 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin
      3-one but susceptible to its benzoxazolinone derivative 6-methoxy-2
      benzoxazolinone. Infection studies of isolated leaves with U. maydis and
      Colletotrichum graminicola provided evidence for coregulation of Umi2 and PR-1
      gene expression, with mRNA levels strongly determined by the extent of fungal
      colonization within tissue. However, in contrast to Umi2, transcript levels of PR
      1 remained low in plants infected with wild-type U. maydis but were 8-fold
      elevated upon infection with an U. maydis mutant strongly attenuated in
      pathogenic development. This suggests that U. maydis colonization in planta
      suppresses a classical defense response. Furthermore, comparative expression
      analysis uncovered distinct transcriptional programs operating in the host in
      response to fungal infection and subsequent tumor formation.

PMID- 15980198
TI  - Specificity in ecological interactions: attack from the same lepidopteran
      herbivore results in species-specific transcriptional responses in two
      solanaceous host plants.
AB  - Model systems have proven enormously useful in elucidating the biochemical
      function of plant genes. However their ecological function, having been sculpted
      by evolutionary forces specific to a species, may be less conserved across taxa.
      Responses to wounding and herbivore attack differ among plant families and are
      known to be mediated by oxylipin, ethylene, and systemin-signaling networks. We
      analyzed transcriptional responses of two native Solanaceous species to the
      attack of an herbivore whose elicitors are known not to be influenced by diet.
      With The Institute for Genomic Research 10k-cDNA potato (Solanum tuberosum)
      microarray, we compared the transcriptional responses of Nicotiana attenuata with
      those of black nightshade (Solanum nigrum) when both were attacked by the
      Solanaceous generalist herbivore, Manduca sexta. Based on an NADH dehydrogenase
      subunit F phylogeny, S. nigrum is more closely related to potato than N.
      attenuata but responded significantly less to M. sexta attack. Apart from
      transcriptional differences anticipated from their differences in secondary
      metabolism, both species showed distinct transcriptional patterns (with only 10%
      overlap in significantly regulated genes), which point to fundamental differences
      in the signaling cascades and downstream genes mediating herbivore resistance.
      The lackluster transcriptional response of S. nigrum could not be attributed to
      its inability to respond to elicitation, because methyl jasmonate elicitation of
      S. nigrum resulted in a strong transcriptional response. Given that attack from
      the same herbivore elicits profoundly different responses in two Solanaceaous
      taxa, we conclude that blueprints for commonly regulated responses to plant
      herbivore interactions appear unlikely.

PMID- 15980199
TI  - Interacting proteins and differences in nuclear transport reveal specific
      functions for the NAP1 family proteins in plants.
AB  - Nucleosome assembly protein 1 (NAP1) is conserved from yeast to human and
      facilitates the in vitro assembly of nucleosomes as a histone chaperone.
      Inconsistent with their proposed function in the nucleus, however, many NAP1
      proteins had been reported to localize in the cytoplasm. We investigated the
      subcellular localization of tobacco (Nicotiana tabacum) and rice (Oryza sativa)
      NAP1 family proteins first by identification of interacting partners and by
      direct examination of the localization of green fluorescent protein-tagged
      proteins. Through treatment of tobacco cells with leptomycin B and mutagenesis of
      nuclear export signal, we demonstrated that Nicta;NAP1;1 and Orysa;NAP1;1 shuttle
      between the cytoplasm and the nucleus. Together with the demonstration that
      tobacco NAP1 proteins bind histone H2A and H2B, our results support the current
      model and provide additional evidence that function of NAP1 as histone chaperones
      appears to be conserved in plants. In addition, we show that tobacco NAP1
      proteins interact with tubulin and the mitotic cyclin Nicta;CYCB1;1, suggesting a
      role for NAP1 in microtubule dynamics. Interestingly, in spite of their high
      homology with the above NAP1 proteins, the other three tobacco proteins and
      Orysa;NAP1;2 did not show nucleocytoplasmic shuttling and were localized only in
      the cytoplasm. Moreover, Orysa;NAP1;3 that lacks a typical nuclear localization
      signal sequence was localized in both the cytoplasm and the nucleus. Finally, we
      show that only Orysa;NAP1;3 could be phosphorylated by casein kinase 2alpha in
      vitro. However, this phosphorylation was not responsible for nuclear import of
      Orysa;NAP1;3 as being demonstrated through mutagenesis studies. Together, our
      results provide an important step toward elucidating the molecular mechanism of
      function of the NAP1 family proteins in plants.

PMID- 15980200
TI  - Fatty acid hydroperoxides and H2O2 in the execution of hypersensitive cell death
      in tobacco leaves.
AB  - We initially compared lipid peroxidation profiles in tobacco (Nicotiana tabacum)
      leaves during different cell death events. An upstream oxylipin assay was used to
      discriminate reactive oxygen species (ROS)-mediated lipid peroxidation from 9-
      and 13-lipoxygenase (LOX)-dependent lipid peroxidation. Free radical-mediated
      membrane peroxidation was measured during H(2)O(2)-dependent cell death in leaves
      of catalase-deficient plants. Taking advantage of these transgenic plants, we
      demonstrate that, under light conditions, H(2)O(2) plays an essential role in the
      execution of cell death triggered by an elicitor, cryptogein, which provokes a
      similar ROS-mediated lipid peroxidation. Under dark conditions, however, cell
      death induction by cryptogein was independent of H(2)O(2) and accompanied by
      products of the 9-LOX pathway. In the hypersensitive response induced by the
      avirulent pathogen Pseudomonas syringae pv syringae, both 9-LOX and oxidative
      processes operated concurrently, with ROS-mediated lipid peroxidation prevailing
      in the light. Our results demonstrate, therefore, the tight interplay between
      H(2)O(2) and lipid hydroperoxides and underscore the importance of light during
      the hypersensitive response.

PMID- 15980202
TI  - Thermodynamic battle for photosynthate acquisition between sieve tubes and
      adjoining parenchyma in transport phloem.
AB  - In transport phloem, photoassimilates escaping from the sieve tubes are released
      into the apoplasmic space between sieve element (SE)/companion cell (CC)
      complexes (SE/CCs) and phloem parenchyma cells (PPCs). For uptake respective
      retrieval, PPCs and SE/CCs make use of plasma membrane translocators energized by
      the proton motive force (PMF). Their mutual competitiveness, which essentially
      determines the amount of photoassimilates translocated through the sieve tubes,
      therefore depends on the respective PMFs. We measured the components of the PMF,
      membrane potential and DeltapH, of SE/CCs and PPCs in transport phloem. Membrane
      potentials of SE/CCs and PPCs in tissue slices as well as in intact plants fell
      into two categories. In the first group including apoplasmically phloem-loading
      species (e.g. Vicia, Solanum), the membrane potentials of the SEs are more
      negative than those of the PPCs. In the second group including symplasmically
      phloem-loading species (e.g. Cucurbita, Ocimum), membrane potentials of SEs are
      equal to or slightly more positive than those of PPCs. Pure sieve tube sap
      collected from cut aphid stylets was measured with H(+)-selective
      microelectrodes. Under our experimental conditions, pH of the sieve tube saps was
      around 7.5, which is comparable to the pH of cytoplasmic compartments in
      parenchymatous cells. In conclusion, only the membrane potential appears to be
      relevant for the PMF-determined competition between SE/CCs and PPCs. The findings
      may imply that the axial sinks along the pathway withdraw more photoassimilates
      from the sieve tubes in symplasmically loading species than in apoplasmically
      loading species.

PMID- 15980201
TI  - Vitamin B1 functions as an activator of plant disease resistance.
AB  - Vitamin B(1) (thiamine) is an essential nutrient for humans. Vitamin B(1)
      deficiency causes beriberi, which disturbs the central nervous and circulatory
      systems. In countries in which rice (Oryza sativa) is a major food, thiamine
      deficiency is prevalent because polishing of rice removes most of the thiamine in
      the grain. We demonstrate here that thiamine, in addition to its nutritional
      value, induces systemic acquired resistance (SAR) in plants. Thiamine-treated
      rice, Arabidopsis (Arabidopsis thaliana), and vegetable crop plants showed
      resistance to fungal, bacterial, and viral infections. Thiamine treatment induces
      the transient expression of pathogenesis-related (PR) genes in rice and other
      plants. In addition, thiamine treatment potentiates stronger and more rapid PR
      gene expression and the up-regulation of protein kinase C activity. The effects
      of thiamine on disease resistance and defense-related gene expression mobilize
      systemically throughout the plant and last for more than 15 d after treatment.
      Treatment of Arabidopsis ecotype Columbia-0 plants with thiamine resulted in the
      activation of PR-1 but not PDF1.2. Furthermore, thiamine prevented bacterial
      infection in Arabidopsis mutants insensitive to jasmonic acid or ethylene but not
      in mutants impaired in the SAR transduction pathway. These results clearly
      demonstrate that thiamine induces SAR in plants through the salicylic acid and
      Ca(2+)-related signaling pathways. The findings provide a novel paradigm for
      developing alternative strategies for the control of plant diseases.

PMID- 15980203
TI  - Differences in cell death induction by Phytophthora Elicitins are determined by
      signal components downstream of MAP kinase kinase in different species of
      Nicotiana and cultivars of Brassica rapa and Raphanus sativus.
AB  - Elicitins are small, secreted proteins produced by species of the plant
      pathogenic oomycete Phytophthora. They induce hypersensitive cell death in most
      Nicotiana species and in some cultivars of Brassica rapa and Raphanus sativus. In
      this study, two true-breeding Fast Cycling B. rapa lines were established that
      showed severe necrosis (line 7-R) or no visible response (line 18-NR) after
      treatment with elicitin. Unexpectedly, microscopic examination revealed localized
      cell death in line 18-NR plants, and expression levels of various defense-marker
      genes were comparable in both lines. These results suggested that both
      "responsive" and "nonresponsive" plants responded to elicitin but differed in the
      extent of the cell death response. Expression of a constitutively active form of
      Arabidopsis (Arabidopsis thaliana) MAP kinase kinase 4 (AtMEK4(DD)) also induced
      rapid development of confluent cell death in line 7-R, whereas line 18-NR showed
      no visible cell death. Similarly, elicitin-responsive Nicotiana species and R.
      sativus cultivars showed significantly stronger cell death responses following
      expression of AtMEK4(DD) compared with nonresponsive species/cultivars. Line 7-R
      also showed higher sensitivity to toxin-containing culture filtrates produced by
      Alternaria brassicicola, and toxin sensitivity cosegregated with elicitin
      responsiveness, suggesting that the downstream responses induced by elicitin and
      Alternaria toxin share factors that control the extent of cell death.
      Interestingly, elicitin responsiveness was shown to correlate with greater
      susceptibility to A. brassicicola (a necrotroph) in B. rapa but less
      susceptibility to Phytophthora nicotianae (a hemibiotroph) in Nicotiana,
      suggesting a more extensive cell death response could cause opposite effects on
      the outcomes of biotrophic versus necrotrophic plant-pathogen interactions.

PMID- 15980204
TI  - Isolation of a protein interacting with Vfphot1a in guard cells of Vicia faba.
AB  - A recent study has demonstrated that phototropins act as blue light receptors in
      stomatal guard cells. However, the downstream components responsible for
      phototropin signaling are largely unknown. In this study, using a yeast two
      hybrid system, we isolated a Vicia faba protein that has a high similarity to
      dynein light chain in the C terminus, which interacts with Vicia faba phototropin
      1a (Vfphot1a). Protein-blot and two-hybrid analyses revealed that Vfphot1a
      interacting protein (VfPIP) bound to the N-terminal [corrected] region of
      Vfphot1a but did not bind to Vfphot1b. The interaction between VfPIP and Vfphot
      was indicated by a pull-down assay. Northern analysis revealed that the
      transcription level of VfPIP gene was more abundant in guard cells than in other
      tissues or cell types. The transiently expressed fusion protein of VfPIP-green
      fluorescent protein was localized on cortical microtubules in Vicia guard cells.
      Microtubule-depolymerizing herbicides partially inhibited both blue light
      dependent H(+) pumping in Vicia guard cell protoplasts and stomatal opening in
      the Vicia epidermis. From these results, we conclude that VfPIP may act as a
      downstream component of phototropin (Vfphot1a) in blue light signaling in guard
      cells. The possible role of VfPIP in blue light signaling of guard cells is
      discussed.

PMID- 15980205
TI  - Quantitation of hemodynamic function during developmental vascular regression in
      the mouse eye.
AB  - PURPOSE: Ultrasound biomicroscopy (UBM) utilizes frequencies higher than
      conventional diagnostic ultrasound and can noninvasively provide anatomic and
      functional information about mouse ocular structures in vivo at high resolution.
      Vascular development can also be assessed with high-frequency Doppler imaging,
      which permits detection and characterization of ocular blood flow not detectable
      at lower, conventional Doppler frequencies. METHODS: The eyes of CD-1 mice were
      examined daily from the day of birth to postnatal day (P)16. Hyaloid vascular
      system anatomy was imaged with UBM and microcomputed tomography (microCT). Blood
      flow velocity was also measured with Doppler UBM imaging in the hyaloid artery,
      vasa hyaloidea propria, tunica vasculosa lentis, and retina. RESULTS: In the
      mouse, the hyaloid vasculature degenerated from a well-defined structure at birth
      by progressive loss of branches. Hyaloid regression coincided with a progressive
      decrease in blood velocity detected in the hyaloid vascular structures, which is
      thought to be one of the major triggering factors of the regression in these
      vessels. At P13, no further blood flow was detected in the CD-1 mouse hyaloid
      vasculature. An inverse relationship was also shown between peak blood velocity
      in the lens and retina. CONCLUSIONS: UBM imaging provides a valuable means of
      rapidly and noninvasively characterizing ocular development in vivo. MicroCT
      scans have also provided intralumenal images of hyaloid vascular structure. This
      is the first study of vascular structure and function during the dynamic process
      of hyaloid vascular regression during mouse neonatal eye development and the
      first three-dimensional images of the complex hyaloid vascular structure.

PMID- 15980206
TI  - In a matter of minutes, the eye can know which way to grow.
AB  - PURPOSE: The fitting of chick eyes with positive or negative lenses causes eye
      growth to decelerate or accelerate, respectively, thereby minimizing the imposed
      blur. This study was conducted to determine whether the eye can initially assess
      the correct direction of growth or whether it relies on trial and error,
      reversing its direction if the magnitude of blur increases. The rapid changes in
      choroidal thickness in response to brief periods of defocus were measured.
      METHODS: After their eyes were measured by ultrasound biometry, chicks wore
      either a +10-D lens over one eye for 10 minutes while restrained in the center of
      a 60-cm drum (to ensure myopic blur), or a negative lens (-7 or -8.6 D) over one
      eye for 10 minutes or 1 hour in a normal cage environment. They were then kept in
      darkness until they were remeasured 2 hours, 1 day, or 2 days after the first
      measurement. Other chicks wore +10 or -8.6-D lenses briefly and were measured
      several times over the next 7 hours in darkness. RESULTS: Wearing positive or
      negative lenses for only 10 minutes produced significantly different effects on
      choroidal thickness measured 2 hours later. Wearing positive lenses for 10
      minutes caused an increase in choroidal thickness (in 28 of 32 eyes) and a
      concomitant decrease in vitreous chamber depth, relative to the amount of change
      in the untreated fellow eye over the same period. Wearing negative lenses for 1
      hour caused significant changes in the opposite direction. Wearing lenses for 2
      hours resulted in choroidal changes that persisted in darkness for up to 6 hours
      after positive lens wear, but returned to normal after negative lens wear.
      Finally, 1 hour of positive lens wear caused significant inhibition of ocular
      elongation over the next 2 days. CONCLUSIONS: The eyes of chicks require only a
      brief period of lens wear to initiate compensation in the appropriate direction.
      Because the refractive status changes little during the period of lens wear, the
      authors conclude that eyes can rapidly determine the sign of the imposed blur
      without resorting to a trial-and-error method.

PMID- 15980207
TI  - Stimulus requirements for the decoding of myopic and hyperopic defocus under
      single and competing defocus conditions in the chicken.
AB  - PURPOSE: The bidirectional nature of emmetropization, as observed in young
      chicks, implies that eyes are able to distinguish between myopic and hyperopic
      focusing errors. In the current study the spatial frequency and contrast
      dependence of this process were investigated in an experimental paradigm that
      allowed strict control over both parameters of the retinal image. Also
      investigated was the influence of accommodation. METHODS: Defocusing stimuli were
      presented through lens-cone devices with attached targets. These devices were
      monocularly applied to 5-day-old chickens for 4 days. Defocus conditions
      included: (1) 7 D of myopic defocus, (2) 7 D of hyperopic defocus, and (3) a
      combination of the two. Two high contrast target designs, a spatially rich,
      striped Maltese cross (target 1) and a standard Maltese cross (target 2) were
      used, except in some experiments where target contrast or spatial frequency
      content was further manipulated. To test the role of accommodation, the treated
      eye of some chicks underwent ciliary nerve section before attachment of the
      device. Refractive error (RE) was measured by retinoscopy and axial ocular
      dimensions measured by A-scan ultrasonography, both in chicks under anesthesia.
      RESULTS: With imposed myopic defocus and high contrast, target 1 elicited
      significantly better compensation than did target 2. With imposed hyperopic
      defocus, both targets elicited near normal compensatory responses. Reducing image
      contrast to 32% for target 2 and to 16% for target 1 precluded compensation for
      myopic defocus, inducing myopia instead. The low-pass-filtered target also
      induced myopia, irrespective of the sign of imposed defocus. With competing
      defocus and intact accommodation, target 1 induced a transient hyperopic growth
      response, whereas myopia was consistently observed with target 2. When
      accommodation was rendered inactive, both targets induced myopia under these
      competitive conditions. CONCLUSIONS: Compensation to myopic defocus is critically
      dependent on the inclusion of middle to high spatial frequencies in the stimulus
      and has a spatial frequency-dependent threshold contrast requirement. With
      competing myopic and hyperopic defocus, the former transiently dominates the
      latter as a determinant of ocular growth, provided that the stimulus conditions
      include sufficient middle to high spatial frequency information and that
      accommodation cues are available.

PMID- 15980208
TI  - Concurrent loss of chromosome arm 1p and chromosome 3 predicts a decreased
      disease-free survival in uveal melanoma patients.
AB  - PURPOSE: Uveal melanoma is a highly malignant disease with a mortality rate of
      50% at 10 to 15 years. Previous studies have shown that chromosomal changes are
      associated with decreased survival of the patient. However, in these studies the
      small number of tumors analyzed did not allow robust statistical analysis. In the
      present study, the independent numerical changes in chromosomes 1, 3, 6, and 8 on
      disease-free survival (DFS) was assessed in a large series of patients with uveal
      melanoma. METHODS: One hundred twenty tumors from patients with uveal melanoma
      were analyzed for numerical changes in chromosomes 1, 3, 6, and 8, with
      cytogenetic analysis, fluorescent in situ hybridization, and/or comparative
      genomic hybridization. Data were correlated with disease outcome in univariate
      and multivariate analyses, by Kaplan-Meier and Cox regression analyses. RESULTS:
      At a mean follow-up time of 45 months, 42 patients had died or had metastatic
      disease. In the univariate analysis, loss of chromosome 3, gain of 8q, largest
      tumor diameter, or the presence of epithelioid cells was associated with a
      decreased DFS. In the multivariate analysis, the effect of monosomy 3 on survival
      was largely modified by changes in 1p36. Regarding all chromosomal changes, only
      the concurrent loss of the short arm of chromosome 1 and all of chromosome 3 was
      an independent prognostic parameter for disease-free survival (P < 0.001).
      CONCLUSIONS: In uveal melanoma, concurrent loss of the short arm of chromosome 1
      and all of chromosome 3 is an independent predictor of decreased DFS.

PMID- 15980209
TI  - The anatomy of the muscle insertion (scleromuscular junction) of the lateral and
      medial rectus muscle in humans.
AB  - PURPOSE: To analyze the histologic features of the insertion of the medial and
      the lateral rectus muscles in humans. METHODS: Postmortem study performed on 49
      extraocular muscles from 21 subjects without known ocular disease. All muscles
      were obtained no longer than 8 hours after death, after consent for autopsy.
      Thirty-seven lateral recti muscles and 12 medial recti muscles were studied with
      light microscopy (hematoxylin-eosin and Goldner stains) as well as with enzyme
      histochemistry and immunohistochemistry, with monoclonal-human tenascin C
      antibody. RESULTS: Light microscopic studies of muscle insertions of the lateral
      and the medial rectus muscle demonstrated muscle tissue connecting directly to
      the sclera without a tendon. These findings were confirmed immunohistochemically
      with tenascin C-antibody staining. CONCLUSIONS: Based on the results of this
      postmortem study in humans the term "muscle tendon" should be used with caution
      for the insertional area (scleromuscular junction) of the lateral and medial
      extraocular muscles. Light microscopy, histochemistry, and immunohistochemistry
      demonstrate that the tissue at the scleromuscular junction contains striated
      muscle with minimal connective (tendinous) tissue connecting to the sclera. To
      the best of the authors' knowledge, this is the first study in which enzyme
      histochemistry and immunohistochemistry have been used to investigate the anatomy
      of the insertional area (muscle-tendon-sclera junction) of the extraocular
      muscles in humans.

PMID- 15980210
TI  - Autosomal recessive retinitis pigmentosa is associated with mutations in RP1 in
      three consanguineous Pakistani families.
AB  - PURPOSE: To localize and identify the gene and mutations causing autosomal
      recessive retinitis pigmentosa in three consanguineous Pakistani families.
      METHODS: Blood samples were collected and DNA was extracted. A genome-wide scan
      was performed by using 382 polymorphic microsatellite markers on genomic DNA from
      affected and unaffected family members, and lod scores were calculated. RESULTS:
      A genome-wide scan of 25 families gave an hlod = 4.53 with D8S260. Retinitis
      pigmentosa in all three families mapped to a 14.21-cM (21.19-Mb) region on
      chromosome 8 at q11, flanked by D8S532 and D8S260. This region harbors RP1, which
      is known to cause autosomal dominant retinitis pigmentosa. Sequencing of the
      coding exons of RP1 showed mutations in all three families: two single-base
      deletions, c.4703delA and c.5400delA, resulting in a frame shift, and a 4-bp
      insertion, c.1606insTGAA, all causing premature termination of the protein. All
      affected individuals in these families are homozygous for the mutations. Parents
      and siblings heterozygous for the mutant allele did not show any signs or
      symptoms of RP. CONCLUSIONS: These results provide strong evidence that mutations
      in RP1 can result in recessive as well as dominant retinitis pigmentosa. The
      findings suggest that truncation of RP1 before the BIF motif or within the
      terminal portion results in a simple loss of RP1 function, producing a recessive
      inheritance pattern. In contrast, disruption of RP1 within or immediately after
      the BIF domain may result in a protein with a deleterious effect and hence a
      dominant inheritance pattern.

PMID- 15980211
TI  - Photoreceptor mitochondrial tyrosine nitration in experimental uveitis.
AB  - PURPOSE: In experimental autoimmune uveitis (EAU), phagocytes are thought to be
      the primary cells in the initiation and maintenance of pathologic tissue damage
      through the release of cytotoxic agents. Recently, the presence of nitric oxide
      synthase has been shown in mammalian mitochondria. In this study, the effect of
      mitochondrial peroxynitrite on the modification of cellular proteins was
      evaluated in the early phase of uveitis, before the infiltration of leukocytes.
      METHODS: Tyrosine nitration in proteins was detected by UV/Vis (visible)
      absorption and Western blot analysis. The identity of the nitrated protein was
      obtained by liquid chromatography-tandem mass spectrometry. The release of
      cytochrome c was assessed in whole retinal extract and in isolated mitochondria.
      The protein nitration in the inflamed retina was also localized by
      immunohistochemistry. RESULTS: Before the leukocyte infiltration in the early
      phase of EAU, the mitochondria-originated peroxynitrite initiated the
      inflammatory insult by specifically nitrating three mitochondrial proteins. In
      vitro nitration of the control retina by peroxynitrite donor resulted in
      nonspecific nitration of all major retinal proteins. After nitration, cytochrome
      c was displaced from its original binding site in the respiratory chain. Further,
      the nitration appeared to commence in the early phase of inflammation, on
      postimmunization day 5, long before the peak of inflammation on day 14.
      Immunohistochemically, tyrosine-nitrated proteins were localized exclusively in
      the photoreceptor inner segments, which are known to be densely populated with
      mitochondria. CONCLUSIONS: These data indicate that mitochondrial proteins are
      the prime targets of inactivation by the mitochondrial peroxynitrite and that
      photoreceptor mitochondria initiate the subsequent irreversible retinal damage in
      experimental uveitis.

PMID- 15980212
TI  - Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of
      function and impaired cellular trafficking of the cone CNG channel.
AB  - PURPOSE: Achromatopsia 2, an inherited retinal disorder resulting in attenuation
      or loss of cone function, is caused by mutations in the alpha subunit of the cone
      cyclic nucleotide-gated (CNG) channel gene CNGA3. Examination of mutations that
      cluster in the first transmembrane segment of the protein may provide insight
      into its role in CNG channel structure, function, biogenesis, and
      pathophysiology. METHODS: The human CNGA3 gene was tagged at the C terminus with
      green fluorescent protein. Four mutations, Y181C, N182Y, L186F, and C191Y, were
      expressed in human embryonic kidney cells. Protein expression was evaluated with
      immunoblot analysis and cellular localization was determined by
      immunocytochemistry. Channel function was evaluated by patch-clamp
      electrophysiology. RESULTS: All the mutations result in loss of channel function,
      as determined by the failure of cGMP to activate wild-type currents in excised
      patches. Full-length mutant proteins were synthesized but retained in the
      endoplasmic reticulum. Glycerol treatment did not rescue channel function nor did
      coexpression with CNGB3, a subunit of native hetero-tetrameric cone channels. A
      control mutant, C191S, exhibited cGMP current activation with significantly
      reduced cooperativity, suggesting that mutations in the first transmembrane
      domain alter in inter- or intrasubunit communication. CONCLUSIONS: The results
      implicate the first transmembrane segment in both maturation and function of CNG
      channels. The defects are not reversed with glycerol, a chemical chaperone that
      rescues channel function in some channelopathies. Molecular analysis of
      achromatopsia 2 mutations may be useful in evaluating potential therapeutic
      approaches for treatment of this channelopathy.

PMID- 15980213
TI  - Mouse retina has oligonucleotide-induced gene repair activity.
AB  - PURPOSE: To test the ability of murine retinal nuclear extracts to support in
      vitro oligonucleotide-mediated gene repair (OMGR)-a prerequisite to repairing
      endogenous gene lesions underlying inherited diseases of the neurosensory retina.
      METHODS: An in vitro reaction assayed whether retinal extract and
      oligonucleotides could correct a mutation in an antibiotic (tetracycline)
      resistance gene in a plasmid. The in vitro gene repair reaction combined plasmid,
      repair oligonucleotide, and nuclear extract. Site-specific repair of the
      tetracycline gene point mutation was revealed in a bacterial readout system in
      which plasmid from the in vitro reaction was recovered and electroporated into
      Escherichia coli. Colony growth on tetracycline indicated repair of the point
      mutation. To confirm site-specific nucleotide repair, plasmids were sequenced or
      subjected to restriction fragment length polymorphism (RFLP) analysis. RESULTS:
      To quantify repair incidence, tetracycline-resistant colonies were normalized to
      ampicillin-resistant colonies. A repair oligonucleotide composed of RNA and DNA
      that contains one mismatched base relative to the target DNA induced an estimated
      1 in 10(4) plasmids to be converted to wild type. If the extract was eliminated
      or boiled before reaction, no tetracycline-resistant colonies grew. Repair
      incidence increased with the concentration of retinal nuclear extract and
      oligonucleotide. Creating single-strand breaks in the plasmid caused a twofold
      increase in repair incidence. CONCLUSIONS: These in vitro assay data suggest that
      murine retina nuclei contain all the DNA repair factors necessary for OMGR, a
      finding that is prerequisite to attempting endogenous gene repair in mouse
      retina.

PMID- 15980214
TI  - Identification of a novel locus on 2q for autosomal dominant high-grade myopia.
AB  - PURPOSE: Myopia, or nearsightedness, is a visual disorder of high and growing
      prevalence in the United States and in other countries. Pathologic high myopia,
      or myopia of </=-6.00 D, predisposes individuals to retinal detachment, macular
      degeneration, cataracts, and glaucoma. Autosomal dominant (AD) nonsyndromic high
      grade myopia has been mapped to loci on 18p11.31, 12q21-q23, 17q21-q23, and 7q36.
      This is the report of significant linkage to a novel locus on the long arm of
      chromosome 2 in a large, multigenerational family with AD high-grade myopia.
      METHODS: The family contains 31 participating members (14 affected). The average
      spherical refractive error for affected individuals was -14.46 D (range, -7.25 to
      -27.00). Before a genome screening was undertaken, linkage to intragenic or
      flanking markers for the myopic genetic syndromes of Stickler syndrome types I,
      II, and III; Marfan syndrome; and juvenile glaucoma were ruled out. In addition,
      no linkage was found to the known AD high-grade myopia loci listed above. A full
      genome screen of the family was performed with 382 microsatellite markers with an
      average intermarker distance of 10 cM. SimWalk2 software was used for multipoint
      linkage analysis based on an AD model with a penetrance of 90% and a disease
      allele frequency of 0.01. RESULTS: Fine-point mapping with an additional nine
      custom-made and five commercial markers yielded a maximum two-point lod score of
      5.67 at marker D2S2348. Results of multipoint analysis indicate that the 1-unit
      support intervals for this new locus spans approximately 9.1 cM from (238.7 to
      247.8 cM) on the chromosome 2 genetic map at q37.1. CONCLUSIONS: A novel locus
      for AD high-grade myopia has been determined, providing further evidence of
      genetic heterogeneity for this disorder.

PMID- 15980215
TI  - Relationship between vision impairment and eye disease to vision-specific quality
      of life and function in rural India: the Aravind Comprehensive Eye Survey.
AB  - PURPOSE: To determine the impact of vision impairment and eye diseases on vision
      specific quality of life and visual function in an older population of rural
      southern India. METHODS: Presenting and best-corrected visual acuity and burden
      of eye diseases were determined in a population aged 40 years and older,
      identified through a random cluster sampling strategy from 50 villages of rural
      south India. A questionnaire validated previously for use in this population was
      used to ascertain quality of life and visual function. Visual acuity measurements
      were obtained with illiterate E Early Treatment Diabetic Retinopathy Study
      (ETDRS) charts. Cataract was graded and defined based on the Lens Opacities
      Classification System (LOCS) III. Macular degeneration was defined based on the
      classification system proposed by the International ARM Epidemiologic Study
      Group. Glaucoma was defined based on results of clinical examinations including
      optic disc and visual fields. Analyses were performed to explore the relationship
      of overall and subscale quality-of-life and visual function scores with
      presenting acuity in the better-seeing eye, specific eye diseases, and
      demographic variables. RESULTS: Information on quality of life and visual
      function were available for 5119 (99.4%) of 5150 study subjects. The mean
      presenting visual acuity in the better eye was 0.76 +/- 0.53 logMAR (logarithm of
      the minimum angle of resolution) units. Age, education, occupation, presenting
      acuity in the better eye, and presence of a cataract, glaucoma, or refractive
      error were independently associated with overall quality-of-life and vision
      function scores. After adjustment for demographic variables and ocular disease,
      persons with vision impairment or bilateral blindness based on presenting visual
      acuity had lower scores across all domains of quality of life and vision
      function. Scores for subscales of quality-of-life and vision function domains
      were significantly lower among those with age-related cataract and glaucoma
      compared with persons without those eye diseases. CONCLUSIONS: Presenting vision
      in the better eye was associated with quality of life and vision function in this
      older population of rural south India. Subjects with glaucoma and age-related
      cataract had an associated decrease in quality of life and vision function,
      independent of presenting visual acuity in the better eye.

PMID- 15980216
TI  - Overnight thickness variation in diabetic macular edema.
AB  - PURPOSE: To study the evening-to-morning variation in retinal thickness in
      patients with fovea-involving diabetic macular edema. METHODS: Twelve eyes in 12
      patients aged 39 to 78 years (mean, 57) with fovea-involving diabetic macular
      edema and 14 eyes in 7 healthy volunteers aged 30 to 70 years (mean, 57) were
      examined by optical coherence tomography, in the evening and in the morning after
      > or =6 hours of sleep in the recumbent position in darkness followed by 0.5 hour
      wakefulness in the same position in room light with both eyes open. RESULTS: In
      patients with diabetic macular edema, macular thickness increased overnight, from
      316 +/- 72 microm in the evening to 336 +/- 81 microm in the morning (P = 0.003).
      Visual acuity decreased from a mean of 41 ETDRS letters (Early Treatment of
      Diabetic Retinopathy Study; range, 4-61) in the evening, to a mean of 36 letters
      (range, 2-60) in the morning (P = 0.03). No overall change was found in mean
      arterial blood pressure (MABP; P = 0.48), blood glucose (P = 0.25), or corneal
      thickness (P = 0.26). The overnight change in macular thickness correlated
      directly with the change in MABP (r = 0.65, P = 0.03) but not with baseline MABP
      or blood glucose. The overnight increase in retinal thickness remained
      significant after statistical adjustment for the effect of arterial blood
      pressure (P = 0.002). Healthy subjects demonstrated no significant change in any
      parameter. CONCLUSIONS: In fovea-involving diabetic macular edema, a reduction in
      visual acuity accompanies overnight retinal thickening, the magnitude being
      related to the nocturnal change in blood pressure. The results indicate that
      deficient regulation of retinal capillary filling pressure promotes edema, but
      the bulk of the overnight increase in macular edema is caused by other
      mechanisms, of which postural variation in venous blood pressure and increased
      retinal metabolism in the dark merit further study.

PMID- 15980217
TI  - Comparison of ocular component growth curves among refractive error groups in
      children.
AB  - PURPOSE: To compare ocular component growth curves among four refractive error
      groups in children. methods Cycloplegic refractive error was categorized into
      four groups: persistent emmetropia between -0.25 and +1.00 D (exclusive) in both
      the vertical and horizontal meridians on all study visits (n = 194); myopia of at
      least -0.75 D in both meridians on at least one visit (n = 247); persistent
      hyperopia of at least +1.00 D in both meridians on all visits (n = 43); and
      emmetropizing hyperopia of at least +1.00 D in both meridians on at least the
      first but not at all visits (n = 253). Subjects were seen for three visits or
      more between the ages of 6 and 14 years. Growth curves were modeled for the
      persistent emmetropes to describe the relation between age and the ocular
      components and were applied to the other three refractive error groups to
      determine significant differences. results At baseline, eyes of myopes and
      persistent emmetropes differed in vitreous chamber depth, anterior chamber depth,
      axial length, and corneal power and produced growth curves that showed
      differences in the same ocular components. Persistent hyperopes were
      significantly different from persistent emmetropes in most components at
      baseline, whereas growth curve shapes were not significantly different, with the
      exception of anterior chamber depth (slower growth in persistent hyperopes
      compared with emmetropes) and axial length (lesser annual growth per year in
      persistent hyperopes compared with emmetropes). The growth curve shape for
      corneal power was different between the emmetropizing hyperopes and persistent
      emmetropes (increasing corneal power compared with decreasing power in
      emmetropes). conclusions Comparisons of growth curves between persistent
      emmetropes and three other refractive error groups showed that there are many
      similarities in the growth patterns for both the emmetropizing and persistent
      hyperopes, whereas the differences in growth lie mainly between the emmetropes
      and myopes.

PMID- 15980218
TI  - Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural
      Epidemiology Study (CURES) eye study, I.
AB  - PURPOSE: To assess the prevalence of diabetic retinopathy (DR) in type 2 diabetic
      subjects in urban India using four-field stereo color photography. METHODS: The
      Chennai Urban Rural Epidemiology Study (CURES) is a population-based study
      conducted on a representative population of Chennai (formerly Madras) city in
      South India. Individuals > or =20 years in age (n = 26,001) were screened for
      diabetes. Of the 1529 known diabetic subjects, 1382 (90.4%) participated in the
      study. Subjects with newly detected diabetes (n = 354) by the oral glucose
      tolerance test (OGTT) also consented to participate in the study. All the
      subjects underwent four-field stereo color photography, and retinopathy was
      graded in the color fundus photographs according to Early Treatment Diabetic
      Retinopathy Study (ETDRS) criteria. RESULTS: The overall prevalence of DR in the
      population was 17.6% (95% confidence interval [CI]: 15.8-19.5), which included
      20.8% (95% CI: 18.7-23.1) in known diabetic subjects and 5.1% (95% CI: 3.1-8.0)
      in subjects with newly detected diabetes. The prevalence of DR was significantly
      higher in men than in women (21.3% vs. 14.6%; P < 0.0001) and among subjects with
      proteinuria (P = 0.002). Logistic regression analysis showed that for every 5
      year increase in the duration of diabetes, the risk for DR increased 1.89-fold
      (95% CI: 1.679-2.135; P < 0.0001). For every 2% elevation of glycated hemoglobin
      (HbA1c), the risk for DR increased by a factor of 1.7 (95% CI: 1.545-1.980; P <
      0.0001). CONCLUSIONS: This study shows that the prevalence of diabetic
      retinopathy is lower in urban South Indians than in other ethnic groups. However,
      due to the large number of diabetic subjects, DR is likely to pose a public
      health burden in India; hence, routine retinal examination is mandatory to detect
      DR in the early stages.

PMID- 15980219
TI  - Overnight orthokeratology lens wear can inhibit the central stromal edema
      response.
AB  - PURPOSE: To investigate the overnight corneal edema response during overnight
      orthokeratology (OK). METHODS: Eighteen young adult myopic subjects wore reverse
      geometry lenses in Boston XO material (nominal Dk/t 46 x 10(-9) cm.mL
      O2/s.mL.mmHg) on an overnight wearing schedule for 1 month. Another 10 subjects
      wore conventional rigid gas-permeable (GP) lenses of similar Dk/t in one eye
      only, on an identical schedule. Corneal stromal thicknesses in the center,
      midperiphery, and periphery were measured by optical pachometry in the morning
      after lens removal, after 1, 4, 10, and 30 nights of wear. Changes from baseline
      for OK, GP and no-lens eyes were compared by repeated-measures ANOVA and
      protected post hoc t-tests. RESULTS: The central stroma swelled significantly
      less in OK than in GP eyes (P < 0.001, ANOVA), and less than with no lens wear (P
      < 0.001, ANOVA) throughout the study. Overnight edema levels consistent with Dk/t
      were found on day 1 in the midperiphery (3.5 mm from apex) and periphery (5.0 mm)
      with both OK and GP lenses. The overnight edema response decreased significantly
      through the study with both lens types. Recovery to baseline stromal thickness
      during the day was demonstrated for GP eyes and for OK eyes in the central and
      peripheral cornea. CONCLUSIONS: Overnight wear of reverse-geometry OK lenses
      inhibited the central stromal edema response. Overnight edema levels consistent
      with Dk/t were found in the corneal midperiphery and periphery. Adaptation of the
      edema response occurred with continuing overnight lens wear. The results suggest
      that central pressure exerted by the flat-fitting base curve of the OK lens acts
      locally as a "clamp" to inhibit overnight central corneal swelling.

PMID- 15980220
TI  - Decreased corneal sensitivity in patients with dry eye.
AB  - PURPOSE: To explore changes in corneal sensitivity that develop in patients with
      dry eye and the relationship between sensibility and severity of the dry eye
      disease. METHODS: Experiments were performed in 44 patients with dry eye and 42
      healthy individuals. Corneal sensitivity was measured with the Belmonte
      noncontact gas esthesiometer. Mechanical (air jets at flow rates from 0 to 200
      mL/min, reaching the corneal surface at 34 degrees C), thermal (cold or warm air
      at subthreshold flow rates changing corneal basal temperature +/-1 degrees C),
      and chemical stimuli (air containing 0% to 50% CO2 at subthreshold flow rate and
      temperature at the cornea of 34 degrees C) were applied to the center of the
      cornea to determine the sensitivity threshold for each stimulus modality. The
      clinical state of the ocular surface was also explored, measuring the fluorescein
      tear break-up time, the degree of corneal staining with fluorescein and Lissamine
      green, and tear production with the Schirmer test. RESULTS: Both in control
      subjects and patients with dry eye, the corneal thresholds for mechanical,
      chemical, and thermal stimulation increased with age. Moreover, the thresholds
      for the three modalities of stimuli were significantly higher in patients with
      dry eye than in control subjects. In both groups, individual mechanical,
      chemical, and thermal thresholds correlated significantly. Also, high thresholds
      in patients with dry eye correlated with the intensity of fluorescein and
      Lissamine green corneal staining but not with the results of the Schirmer test.
      CONCLUSIONS: Patients with dry eye exhibit corneal hypoesthesia after mechanical,
      thermal, and chemical stimulation that appears to be related to damage to the
      corneal sensory innervation.

PMID- 15980221
TI  - Inhibitory effect of triptolide on chemokine expression induced by
      proinflammatory cytokines in human corneal fibroblasts.
AB  - PURPOSE: Synthesis of various chemokines, including interleukin (IL)-8 and
      monocyte chemotactic protein (MCP)-1, as well as the surface expression of
      intercellular adhesion molecule (ICAM)-1 in corneal fibroblasts contribute to
      corneal inflammation. The effects of triptolide, the major constituent of
      extracts of the herb Tripterygium wilfordii hook f, on the expression of these
      proteins in human corneal fibroblasts were examined in comparison with those of
      dexamethasone. METHODS: The release of IL-8 and MCP-1 from and the surface
      expression of ICAM-1 on cultured corneal fibroblasts were measured with enzyme
      linked immunosorbent assays. The cellular abundance of the mRNAs for these
      proteins was determined by reverse transcription and real-time polymerase chain
      reaction analysis. The activities of the transcription factors NF-kappaB and AP-1
      were assessed by cell transfection with secretory alkaline phosphatase reporter
      genes. RESULTS: Both triptolide and dexamethasone inhibited in a dose-dependent
      manner the expression of IL-8 and MCP-1 in corneal fibroblasts induced by the
      proinflammatory cytokines IL-1beta or tumor necrosis factor (TNF)-alpha. These
      inhibitory effects were apparent at both the mRNA and protein levels. Both
      compounds also had a lesser inhibitory effect on cytokine-induced ICAM-1
      expression. The activation of NF-kappaB by IL-1beta was markedly inhibited by
      both triptolide and dexamethasone, whereas the activity of AP-1 was not affected
      by either agent. CONCLUSIONS: Like dexamethasone, triptolide inhibited IL-8 and
      MCP-1 expression in cultured human corneal fibroblasts exposed to proinflammatory
      cytokines, an action most likely mediated by inhibition of NF-kappaB activation.
      Similar effects of triptolide in vivo may be expected to limit the infiltration
      of neutrophils and monocytes into the cornea.

PMID- 15980222
TI  - Thinning rate of the precorneal and prelens tear films.
AB  - PURPOSE: To apply interferometry as an in vivo measure of tear film thinning
      between blinks. METHODS: Wavelength-dependent interference was used to measure
      the tear film thinning rates in 20 normal contact lens wearers, and spectra were
      captured at a rate of 4.5 per second for 20 seconds. Four recordings of
      precorneal tear film (PCTF) thinning were made, followed by 1 hour of hydrogel
      lens wear and then four recordings of prelens tear film (PLTF) thinning. Subjects
      were asked to blink 1 second after the beginning of the recording and then hold
      their eyes open for an additional 19 seconds, followed by 2 minutes of rest
      between recordings. RESULTS: The average thinning rate of the PLTF was greater
      than that of the PCTF and average initial tear film thickness of the PLTF was
      less than that of the PCTF. For both these reasons, the "tear thinning time"
      (time to reach 0 thickness) was typically shorter for the PLTF than for the PCTF.
      Histograms of PCTF and PLTF thinning rates showed a narrow peak corresponding to
      slow thinning of approximately 1 microm/min, but also many examples of rapid
      thinning of approximately 10 microm/min, with greater variability. Both the
      initial thickness and thinning rate of the PLTF correlated with corresponding
      values for the PCTF, although many more rapidly changing values were associated
      with the PLTF. Plots of rapid thinning of PCTF and PLTF were both linear and were
      not accompanied by any significant increase in thickness of corneal epithelium or
      contact lens, respectively. CONCLUSIONS: Tear film thinning can be analyzed in
      terms of flow in three spatial directions: (1) outward (evaporation), (2) inward
      (into the epithelium or contact lens), and (3) parallel to the tear film surface.
      The results indicate that the second mechanism may be unimportant. Studies have
      shown a range of tear film evaporation rates from 0.24 to 1.45 microm/min,
      whereas, when the lipid layer is washed away from the tear film, the thinning
      rate, due to evaporation, would be approximately 7 microm/min. Thus, slow
      thinning rates may be due to tear film evaporation, whereas rapid rates (which
      are often greater than 7 microm/min) presumably include other mechanisms such as
      dewetting, Marangoni flow (i.e., surface tension gradients), and pressure
      gradient flow.

PMID- 15980223
TI  - Effect of wound type on Smad 2 and 4 translocation.
AB  - PURPOSE: In a prior study, it was reported that both TGF-beta receptors type-I
      and -II are upregulated after wounding, suggesting that TGF-beta signaling may
      play a role in corneal epithelial repair. The Smad proteins, which translocate
      into the nucleus after activation of the TGF-beta receptors, are key factors in
      the major TGF-beta signaling pathway. The present study was undertaken to examine
      whether Smads 2 and 4 translocate into the nucleus during wound repair and
      whether the wound type affects the extent of translocation. METHODS: Either a 3
      mm superficial keratectomy or epithelial debridement was performed on adult
      Sprague-Dawley rats. The eyes were allowed to heal from 4 hours to 2 weeks.
      Indirect immunofluorescence was performed with anti-Smads 2 and 4, anti-laminin,
      a marker of basement membrane, and anti-alphavbeta6 integrin, which has been
      implicated in TGF-beta activation. In addition, the effect of the p38MAPK
      inhibitor SB202190 on healing rates of debridement and keratectomy wounds was
      determined in organ culture. RESULTS: In unwounded tissue, Smad 2 was
      cytoplasmic. By 4 hours after keratectomy, nuclear localization was visible in a
      few epithelial basal cells at the leading edge of the wound. The number of basal
      cells expressing nuclear Smad 2 in the wound area increased with time, peaking at
      48 hours (95%). However, in the debridement model, Smad 2 localization remained
      primarily cytoplasmic. Smad 4 showed similar localization. In both wound models,
      p38MAPK inhibitor slowed epithelial migration, and alphavbeta6 integrin appeared
      to be upregulated with localization primarily observed in the basal cells
      migrating over the wound area. CONCLUSIONS: The presence of the basement membrane
      appears to have an effect on the extent and duration of translocation of the Smad
      2 and 4 proteins during corneal epithelial wound repair. The Smad pathway does
      not appear to be essential for migration; rather, it may play a role in
      resynthesis of the basement membrane.

PMID- 15980224
TI  - Corneal keratocytes: phenotypic and species differences in abundant protein
      expression and in vitro light-scattering.
AB  - PURPOSE: Previous studies suggest that corneal haze after injury involves changes
      in the light-scattering properties of keratocytes that are possibly linked to the
      abundant expression of water-soluble proteins. The purpose of this study was to
      determine the protein expression pattern of keratocytes from different species
      and different cultured rabbit keratocyte phenotypes and to assess differences in
      light-scattering in vitro. METHODS: Water-soluble proteins were isolated from
      corneal epithelial cells and keratocytes of several species, including human
      (Hu), mouse (Mo), rabbit (Ra), chicken (Ch), and pig (P) and different cultured
      rabbit keratocyte phenotypes. Proteins were then characterized by SDS-PAGE,
      tryptic peptide sequence analysis, and Western blot analysis. Light-scattering
      and actin organization from cultured cells were determined with confocal
      reflectance and fluorescence microscopy, respectively. RESULTS: Protein
      expression patterns varied substantially between species and cell types, with
      five new abundantly expressed proteins identified including, LDH (Ra, Ch), G3PDH
      (Hu, Ch), pyruvate kinase (Ch), Annexin II (Ch), and protein disulfide isomerase
      (Ch). Different rabbit keratocyte phenotypes also showed different levels of
      expression of ALDH1A1 and TKT, with myofibroblasts showing the greatest
      reduction. Myofibroblasts showed significantly greater (P < 0.05) light
      scattering but also showed the greatest organization of actin filaments.
      CONCLUSIONS: Abundant protein expression is a characteristic feature of corneal
      keratocytes that is lost when cells are phenotypically modulated in culture.
      Greater light-scattering by myofibroblasts also provides support for a link
      between cellular transparency and haze after injury that is possibly related to
      loss of protein expression or development of prominent actin filament bundles.

PMID- 15980225
TI  - D-beta-hydroxybutyrate protects against corneal epithelial disorders in a rat dry
      eye model with jogging board.
AB  - PURPOSE: The purpose of this study was to establish a rat dry eye model of
      corneal epithelial disorders by inducing improper tear dynamics and change in
      blink frequency. The protective effect of d-beta-hydroxybutyrate (HBA) on the
      corneal epithelia was also investigated. METHODS: A series of treatments were
      performed under continuous exposure to low-humidity airflow. Rats were placed on
      a jogging board (JB) made of a plastic pipe for 7.5 h/d, and, for 16.5 hours,
      they were placed in individual cages without JB treatment. The resultant changes
      in tear dynamics and corneal epithelial structure were then analyzed. Five days
      after the rats were exposed to the treatment, eyes that showed corneal
      fluorescein staining were examined, to investigate the effect of HBA, by
      administration of eye drops containing 80 mM HBA four times daily during JB
      treatment for 5 days. RESULTS: Significant reductions in blink frequency,
      Schirmer score, and tear clearance were recorded during JB treatment in eyes that
      showed persistent punctate staining of almost one half of the corneal surface.
      The application of HBA-containing eye drops significantly reduced the punctate
      staining compared with the initial or phosphate-buffered saline-treated eyes.
      CONCLUSIONS: This rat dry eye model, established by repeated JB treatment in
      desiccating conditions, induced abnormal tear dynamics and superficial punctate
      keratopathy similar to that in humans. These findings suggest the potential
      clinical application of HBA in corneal surface epithelial disorders in patients
      with moderate to mild dry eye.

PMID- 15980226
TI  - Thymosin-beta4 modulates corneal matrix metalloproteinase levels and
      polymorphonuclear cell infiltration after alkali injury.
AB  - PURPOSE: Corneal alkali injury is highly caustic, and present clinical therapies
      are limited. The purpose of this study was to investigate the ability of thymosin
      beta4 (Taubeta4) to promote healing in an alkali injury model and the mechanisms
      involved in that process. METHODS: Corneas of BALB/c mice were injured with NaOH,
      irrigated copiously with PBS, and treated topically with either Tbeta4 or PBS
      twice daily. At various time points after injury (PI), corneas from the Tbeta4-
      versus the PBS-treated group were examined for polymorphonuclear leukocyte (PMN)
      infiltration, chemokine, and matrix metalloproteinase (MMP)/tissue inhibitor of
      metalloproteinase (TIMP) expression. RESULTS: Tbeta4-treated corneas demonstrated
      improved corneal clarity at day 7 PI. Whereas Tbeta4 decreased corneal MMP-2 and 
      9 and MT6-MMP levels after alkali injury, no change in TIMP-1 and -2 expression
      was detected. Tbeta4 treatment also decreased corneal KC (CXCL1) and macrophage
      inflammatory protein (MIP)-2 chemokine expression and PMN infiltration.
      Immunohistochemistry studies demonstrated MMP-9 expression at the leading edge of
      the epithelial wound, in the the limbus (containing stem cells), and in stromal
      PMNs. CONCLUSIONS: Tbeta4 treatment decreases corneal inflammation and modulates
      the MMP/TIMP balance and thereby promotes corneal wound repair and clarity after
      alkali injury. These results suggest that Tbeta4 may be useful clinically to
      treat severe inflammation-mediated corneal injuries.

PMID- 15980227
TI  - Regulation of 1-cys peroxiredoxin expression in the process of stromal wound
      healing after photorefractive keratectomy.
AB  - PURPOSE: To investigate 1-cys peroxiredoxin (1-cysPrx) expression during the
      corneal wound-healing process after PRK and the effect of growth factors on 1
      cysPrx expression in cultured bovine keratocytes (BKs). METHODS: Rat corneas were
      excised at 4 hours, 12 hours, 1 day, 3 days, and 7 days after PRK. Expression of
      1-cysPrx in the corneas was examined by immunohistochemical, Northern blot, and
      immunoblot analyses. Keratocytes were isolated from bovine corneas and
      subcultured to study the effects of TGF-beta1, keratinocyte growth factor (KGF),
      hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), and H2O2
      on 1-cysPrx expression at different concentrations and time intervals. Generation
      and proliferation of intracellular reactive oxygen species (ROS) in cultured BKs
      stimulated by these growth factors were measured by the DCF (2',7'
      dichlorofluorescein) assay, the CCK-8 assay, and immunoblot analysis with a
      polyclonal proliferating cell nuclear antigen (PCNA) antibody, respectively.
      RESULTS: Intense staining of 1-cysPrx was observed in the epithelia and the
      anterior stromas of wounded corneas 4 hours after PRK and had extended to the
      entire stroma by day 3. By day 7, the expression almost returned to nonsurgical
      control level in epithelia, although notable expression was still detectable in
      the stroma. Concomitant augmentation of 1-cysPrx mRNA and protein was seen in the
      corneas at 12 hours to 7 days. Growth factor treatment in cultured BKs resulted
      in 1-cysPrx induction in a dose- and time-dependent manner. Growth factor
      stimulated cells showed strong DCF fluorescence and increased proliferation
      during a 24-hour incubation, during which an upregulation of 1-cysPrx occurred.
      CONCLUSIONS: These observations provide new information for the regulation of 1
      cysPrx expression during the corneal wound-healing process.

PMID- 15980228
TI  - Molecular cloning and expression profiling of optineurin in the rhesus monkey.
AB  - PURPOSE: It has been shown that mutations in the optineurin (OPTN) gene are
      involved in the etiology of adult-onset primary open-angle glaucoma (POAG). In
      view of close similarities between human and nonhuman primate ocular development
      and function, the rhesus monkey is considered a suitable model for human visual
      system research. Therefore, this study was conducted to clone the orthologue of
      the human OPTN gene in the rhesus monkey (Rh-OPTN) and to determine its genomic
      organization. A further purpose was to establish Rh-OPTN protein expression
      profiles and tissue distribution in the rhesus anterior segment, retina, and
      optic nerve. METHODS: The Rh-OPTN gene was cloned and its genomic structure
      determined. The mRNA expression pattern was examined by Northern blot analysis.
      The protein's cellular localization, ocular expression, and tissue distribution
      were established by immunolabeling. RESULTS: The Rh-OPTN gene has 13 exons and
      encodes for a 571-amino-acid protein. Both cDNA and amino acid sequences are 96%
      identical with the human OPTN. Northern blot analysis revealed prominent
      expression of two different transcripts in heart, brain, kidney, lung, spleen,
      skeletal muscle, and small intestine. Cellular and tissue distribution of Rh-OPTN
      protein were highly similar to its human and mouse homologous proteins.
      CONCLUSIONS: The optineurin gene and protein are evolutionary conserved between
      humans and the rhesus monkey. High similarity of ocular expression and tissue
      distribution between the two optineurin proteins suggests that this nonhuman
      primate is a suitable model for the pathophysiology and treatment of human
      glaucomatous optic neuropathy.

PMID- 15980229
TI  - The pattern electroretinogram in glaucoma patients with confirmed visual field
      deficits.
AB  - PURPOSE: To better understand the relationship between the amplitude of the
      pattern electroretinogram (PERG) and visual loss, measured with static automated
      perimetry. METHODS: Transient PERGs were recorded in 15 patients (31-77 years)
      and 16 normal individuals (26-65 years). An eye was considered to have
      glaucomatous damage only if there was an abnormal disc, an abnormal 24-2 Humphrey
      visual field result (pattern stand deviation, glaucoma hemifield test, and
      cluster) and an abnormal multifocal visual evoked potential. All the worse (more
      affected) eyes of the patients and six of the better eyes met these criteria. The
      N95 amplitude of the PERG was measured from the positive peak (P50) at
      approximately 50 ms to the trough at approximately 95 ms. The ratio of N95 to P50
      the N95 amplitude divided by the P50 amplitude-was also measured. RESULTS: First,
      the PERG was within normal limits for 4 (26.7%) of the worse eyes. Overall, 6
      (28.6%) of the 21 eyes that met the criteria for glaucomatous damage had normal
      PERGs on both PERG measures. Because the normal individuals were younger than the
      patients, an even larger number of normal PERGs might be expected with an age
      appropriate control group. Second, the N95 amplitude was nonlinearly related to
      visual field sensitivity when sensitivity was plotted on a linear plot. Small
      field losses were associated with disproportionately large losses in PERG
      amplitude. Third, the PERG from both eyes of a patient were very similar, even
      when the visual fields suggested very different levels of damage. CONCLUSIONS:
      These results are consistent with the view that very early damage can affect the
      PERG, even before the visual field shows a loss. At the same time, it is clear
      that patients with clear glaucomatous damage can have normal-appearing PERGs. An
      explanation is proposed to account for these findings.

PMID- 15980230
TI  - Accuracy of intraocular pressure measurements in new zealand white rabbits.
AB  - PURPOSE: Rabbits are commonly used for the evaluation of drugs and surgery to
      lower intraocular pressure (IOP). The accuracy of intraocular pressure
      measurement is therefore critical in the analysis of data and subsequent
      extrapolation to humans. The purpose of this study was to establish the most
      reliable technique, from several currently available methods, of measuring IOP in
      New Zealand White rabbits. METHODS: The IOPs of 11 healthy New Zealand White
      rabbits were measured with a fluid-filled pressure transducer system that was
      connected to the anterior chamber of each animal so that the IOP could be varied
      by altering the height of a bottle of balanced salt solution. Intraocular
      pressures were recorded over a range of 50 to 0 mm Hg by the transducer system,
      and comparative measurements at the same pressures were performed with the
      Tonopen XL (Mentor, Norwell, MA), the Perkins handheld applanation tonometer
      (Clement Clarke, Harlow, UK), and the Ocular Blood Flow (OBF) pneumatonometer
      (OBF Laboratories, Wiltshire, UK). RESULTS: All three tonometers underestimated
      the true IOP, especially at higher pressures. Although the mean difference in
      actual and tonometric IOP was least in the Tonopen XL, there was a high degree of
      variability through the entire range of IOPs measured. The Perkins tonometer,
      although slightly less accurate than the Tonopen XL, was more consistent in
      measurement. The OBF pneumatonometer was the least-reliable estimate of IOP.
      CONCLUSIONS: All tonometers underestimate IOP, with increasing inaccuracy at
      higher pressures. The Perkins applanation tonometer was the most reliable for
      measuring IOP in the range of 0 to 50 mm Hg in New Zealand White rabbits.

PMID- 15980231
TI  - Effects of cholesterol-lowering statins on the aqueous humor outflow pathway.
AB  - PURPOSE: To investigate the effects of cholesterol-lowering statin drugs on
      trabecular meshwork cellular properties and aqueous humor outflow. METHODS:
      Primary cell cultures of porcine trabecular meshwork (PTM) and ciliary body (PCB)
      were treated with either lovastatin or compactin, to determine the effects of
      statins on cell shape, actin cytoskeletal organization, and cell-extracellular
      matrix interactions (focal adhesions) by immunofluorescence staining. Changes in
      myosin light-chain (MLC) phosphorylation were evaluated by Western blot analysis.
      Changes in Rho GTPase content of membrane fractions from lovastatin-treated PTM
      cells were assessed by Western blot analysis. A constant-flow, organ-culture
      perfusion system was used to measure the effects of statins on aqueous humor
      outflow facility in the anterior segments of porcine eyes. RESULTS: PTM and PCB
      cells treated with lovastatin or compactin exhibited dramatic changes in cell
      shape and cytoskeletal organization within 24 hours, consisting of cell rounding,
      actin depolymerization, and decreased focal adhesions. These effects were found
      to be reversible on supplementation with geranylgeranyl pyrophosphate. Both
      lovastatin and compactin decreased MLC phosphorylation in PTM and PCB cells. PTM
      cells treated with lovastatin exhibited marked decreases in membrane-bound Rho
      GTPase. In addition, perfusion of organ-cultured porcine eye anterior segments
      with 100 microM lovastatin for 96 hours caused a significant increase in aqueous
      humor outflow facility (110%) compared with control eyes, in a reversible manner.
      CONCLUSIONS: This study demonstrates that the statin drugs lovastatin and
      compactin induce changes in cell shape and actin cytoskeletal organization and
      decrease MLC phosphorylation in PTM and PCB cells, all of which are events that
      are likely to lead to cellular and tissue relaxation. In addition, these effects
      of the statins appear to be mediated by inhibition of isoprenylation of the small
      GTP-binding proteins such as Rho GTPase. An important finding is that statins
      exert an ocular hypotensive response in an organ-culture perfusion model,
      indicating the potential for this class of drugs in glaucoma therapy.

PMID- 15980232
TI  - Relationship of SITA and full-threshold standard perimetry to frequency-doubling
      technology perimetry in glaucoma.
AB  - PURPOSE: To compare full-threshold (FT) and SITA algorithms for standard
      automated perimetry (SAP) with frequency-doubling technology perimetry (FDT) in
      glaucoma, to help clinicians to relate results in patients who have had two or
      more of these tests during follow-up. METHODS: This study was a retrospective
      analysis of data from a longitudinal prospective study at the University of
      California, San Diego. One hundred four eyes of 104 patients with glaucomatous
      optic neuropathy detected by optic disc stereophotographs were included. All
      patients had standard perimetry (SITA and FT) and FDT within 3 months of each
      other. Global indices, abnormality and severity using two threshold algorithms of
      standard perimetry were compared with FDT. RESULTS: More eyes had normal visual
      fields by SAP-FT (57 eyes) than by either SAP-SITA (42 eyes) or FDT (45 eyes),
      although SAP-FT agreed more closely with FDT (kappa = 0.54 +/- 0.08) on the
      presence of a visual field defect than did SAP-SITA (kappa = 0.34 +/- 0.08).
      Correlations of FDT to standard perimetry global indices were similar regardless
      of the threshold strategy used for standard perimetry, yielding r2= 0.38-0.57 for
      SAP-FT with FDT, 0.36-0.54 for SAP-SITA with FDT. CONCLUSIONS: Despite many
      similarities of SAP-SITA and SAP-FT, switching the standard of comparison from
      SAP-FT to SAP-SITA changes the relationship to FDT with regard to visual field
      abnormality, but not correlations of global indices. FDT detected abnormal fields
      in more eyes than SAP-FT. SAP-FT tended to detect a subset of eyes found abnormal
      by FDT. Visual field defects may be detected more often by FDT and SAP-SITA in
      eyes with early visual field loss, but these two tests may not agree on which
      eyes show field loss in patients who undergo both tests at follow-up.

PMID- 15980233
TI  - Reproducibility of retinal nerve fiber thickness measurements using the stratus
      OCT in normal and glaucomatous eyes.
AB  - PURPOSE: To determine the reproducibility of Stratus Optical Coherence Tomography
      (OCT) retinal nerve fiber layer (RNFL) measurements around the optic nerve in
      normal and glaucomatous eyes. METHODS: One eye was chosen at random from 88
      normal subjects and 59 glaucomatous subjects distributed among mild, moderate,
      and severe glaucoma, determined by visual field testing. Subjects underwent six
      RNFL thickness measurements performed by a single operator over a 30-minute
      period with a brief rest between sessions. Three scans were taken with the high
      density Standard RNFL protocol, and three were taken with the Fast RNFL protocol,
      alternating between scan protocols. RESULTS: Reliability, as measured by
      intraclass correlation coefficient (ICC), was calculated for the overall mean
      RNFL thickness and for each quadrant. The ICC for the mean Standard RNFL
      thickness (and lower 95% confidence interval [CI]) in normal and glaucomatous
      eyes was 0.97 (0.96 CI) and 0.98 (0.97 CI), respectively. The ICC for the mean
      Fast RNFL thickness in normal and glaucomatous eyes was 0.95 (0.93 CI) and 0.97
      (0.95 CI), respectively. Quadrant ICCs ranged between 0.79 and 0.97, with the
      nasal quadrant being the least reproducible of all four quadrants, using either
      the Standard or Fast RNFL program. The test-retest variability ranged from 3.5
      microm for the average RNFL thickness measurements in normal eyes to 13.8 microm
      for the nasal quadrant measurements in glaucomatous eyes, which appeared to be
      the most variable. CONCLUSIONS: Reproducibility of RNFL measurements using the
      Stratus OCT is excellent in normal and glaucomatous eyes. The nasal quadrant
      appears to be the most variable measurement. Standard RNFL and Fast RNFL scans
      are equally reproducible and yield comparable measurements. These findings have
      implications for the diagnosis of glaucoma and glaucomatous progression.

PMID- 15980234
TI  - In vitro study of inflammatory potential and toxicity profile of latanoprost,
      travoprost, and bimatoprost in conjunctiva-derived epithelial cells.
AB  - PURPOSE: Conjunctiva-derived epithelial cells were used to investigate, in vitro,
      the expression of various inflammation-associated markers known to be
      overexpressed in patients with glaucoma after contact with the three major
      commercially available eye drops containing prostaglandin analogues. The impact
      on cellular viability and apoptosis in the same cell line was evaluated, to
      address the possible proinflammatory and/or toxic origin of the most frequent
      clinical impairments induced by prostanoids (i.e., conjunctival hyperemia).
      METHODS: Conjunctiva-derived cells were treated in vitro with the commercial
      solutions of latanoprost, travoprost, bimatoprost, prostaglandin (PG)F2alpha,
      tumor necrosis factor (TNF)-alpha, and different concentrations of benzalkonium
      chloride (BAC). Expressions of three inflammation- and immune-related markers,
      intercellular adhesion molecule (ICAM)-1, platelet-endothelial cell adhesion
      molecule (PECAM)-1 and HLA DR, were evaluated with flow cytometry after 24 to 72
      hours of contact at low, subtoxic concentrations. Toxicological tests were also
      performed with cold-light cytofluorometry, in which cellular viability and
      apoptosis were evaluated with the neutral red and Hoechst/propidium iodide tests,
      respectively. RESULTS: TNFalpha induced or stimulated expression of the three
      inflammatory markers, whereas the PGF2alpha, latanoprost, travoprost, and
      bimatoprost solutions did not induce an increase in these markers and even
      produced a marked reduction of ICAM-1 and PECAM-1 expression in those solutions
      most concentrated in BAC, thus suggesting a toxic phenomenon in cellular
      membranes induced by the preservative rather than the medication itself.
      Cytotoxic assays confirmed this hypothesis and showed significant toxicity with
      prostaglandin analogues after prolonged contact, proportional to the
      concentration of BAC in the solution and similar to that of the corresponding
      concentration of BAC alone, bimatoprost having both the least concentration of
      BAC and the least cytotoxic in these experimental conditions. CONCLUSIONS: The
      comparison of latanoprost, travoprost, and bimatoprost, in their commercial
      formulations, showed that none of them appeared to induce direct stimulation of
      the inflammatory pathways involving adhesion molecules or class II antigens,
      although these markers have been found ex vivo in conjunctival specimens from
      patients treated with prostaglandins. In fact, their toxicity was mild and seemed
      to be primarily related to the concentration of BAC, their common preservative,
      which may be the major factor responsible for long-term ocular surface reactions
      in patients receiving topical prostaglandins, but most likely is not a factor in
      early and transient conjunctival hyperemia.

PMID- 15980235
TI  - Threshold and variability properties of matrix frequency-doubling technology and
      standard automated perimetry in glaucoma.
AB  - PURPOSE: To compare test results from second-generation Frequency-Doubling
      Technology perimetry (FDT2, Humphrey Matrix; Carl-Zeiss Meditec, Dublin, CA) and
      standard automated perimetry (SAP) in patients with glaucoma. Specifically, to
      examine the relationship between visual field sensitivity and test-retest
      variability and to compare total and pattern deviation probability maps between
      both techniques. METHODS: Fifteen patients with glaucoma who had early to
      moderately advanced visual field loss with SAP (mean MD, -4.0 dB; range, +0.2 to 
      16.1) were enrolled in the study. Patients attended three sessions. During each
      session, one eye was examined twice with FDT2 (24-2 threshold test) and twice
      with SAP (Swedish Interactive Threshold Algorithm [SITA] Standard 24-2 test), in
      random order. We compared threshold values between FDT2 and SAP at test locations
      with similar visual field coordinates. Test-retest variability, established in
      terms of test-retest intervals and standard deviations (SDs), was investigated as
      a function of visual field sensitivity (estimated by baseline threshold and mean
      threshold, respectively). The magnitude of visual field defects apparent in total
      and pattern deviation probability maps were compared between both techniques by
      ordinal scoring. RESULTS: The global visual field indices mean deviation (MD) and
      pattern standard deviation (PSD) of FDT2 and SAP correlated highly (r > 0.8; P <
      0.001). At test locations with high sensitivity (>25 dB with SAP), threshold
      estimates from FDT2 and SAP exhibited a close, linear relationship, with a slope
      of approximately 2.0. However, at test locations with lower sensitivity, the
      relationship was much weaker and ceased to be linear. In comparison with FDT2,
      SAP showed a slightly larger proportion of test locations with absolute defects
      (3.0% vs. 2.2% with SAP and FDT2, respectively, P < 0.001). Whereas SAP showed a
      significant increase in test-retest variability at test locations with lower
      sensitivity (P < 0.001), there was no relationship between variability and
      sensitivity with FDT2 (P = 0.46). In comparison with SAP, FDT2 exhibited narrower
      test-retest intervals at test locations with lower sensitivity (SAP thresholds
      <25 dB). A comparison of the total and pattern deviation maps between both
      techniques showed that the total deviation analyses of FDT2 may slightly
      underestimate the visual field loss apparent with SAP. However, the pattern
      deviation maps of both instruments agreed well with each other. CONCLUSIONS: The
      test-retest variability of FDT2 is uniform over the measurement range of the
      instrument. These properties may provide advantages for the monitoring of
      patients with glaucoma that should be investigated in longitudinal studies.

PMID- 15980236
TI  - Down-regulation of IFN-gamma-producing CD56+ T cells after combined low-dose
      cyclosporine/prednisone treatment in patients with Behcet's uveitis.
AB  - PURPOSE: To investigate the effects of combined low-dose cyclosporine and
      prednisone (Cs/Pd) treatment on circulating CD56+ T cells in patients with
      Behcet's uveitis. METHODS: Ten patients with Behcet's uveitis and 10 healthy
      control subjects were prospectively recruited. The patients were treated with
      Cs/Pd for 2 months. Phenotypic and functional changes in circulating CD56+ T
      cells were assayed before and after treatment. CD56+ T-cell subsets were
      determined by flow cytometric analysis with monoclonal antibodies for CD3, CD4,
      CD8, CD56, pan gammadelta TCR, and Valpha24. The absolute numbers of cells in the
      lymphocyte subsets were calculated. Cytokine (IFN-gamma, IL-4, and IL-10)
      expressions were measured by ELISA and by intracellular cytokine staining.
      RESULTS: The proportions of CD56+ T cells, specifically CD8highCD56+ and
      CD56+gammadelta T-cell subsets, were significantly higher in active Behcet's
      uveitis but normalized after treatment, whereas the total T-lymphocyte count and
      the absolute numbers of CD56- T cells were unaffected by treatment. The levels of
      IFN-gamma and IL-4 were elevated in aqueous humor and serum in Behcet's uveitis
      (P < 0.001), whereas IL-10 was not detected. After treatment, serum IL-4 levels
      markedly increased (P < 0.001), and IFN-gamma production by circulating CD56+ T
      cells was then suppressed. IL-4 and -10 production by CD56+ T cells was increased
      by treatment, but in contrast, minimal changes were found in CD56- T cells.
      CONCLUSIONS: The results imply that Cs/Pd treatment for Behcet's uveitis
      selectively affects the population of and the cytokine expression in CD56+ T
      cells, but without significant changes in CD56- T cells, and that IFN-gamma
      producing CD56+ T cells are the central pathogenic immune cells in Behcet's
      uveitis.

PMID- 15980237
TI  - T-cell recognition and cytokine profile induced by melanocyte epitopes in
      patients with HLA-DRB1*0405-positive and -negative Vogt-Koyanagi-Harada uveitis.
AB  - PURPOSE: Vogt-Koyanagi-Harada disease (VKH), an autoimmune disease targeted
      against melanocytes, is associated with HLA-DRB1*0405. This study was undertaken
      to analyze T-cell recognition and the cytokine expression profile induced by
      melanocyte epitopes in HLA-DRB1*0405-positive and -negative patients with VKH
      uveitis. METHODS: Peripheral blood mononuclear cells (PBMC) proliferation and Th1
      (IFN-gamma) and Th2 (IL-4 and IL-5) cytokine production were analyzed in HLA
      DRB1*0405-positive (n = 12) and -negative (n = 22) patients with VKH and HLA
      DRB1*0405-positive (n = 9) and -negative (n = 8) control subjects in response to
      human melanoma cell line lysate (HMCLL) and 28 synthetic peptides derived from
      the human melanocyte differentiation proteins TYR, TRP1, TRP2, and Pmel17. The
      peptides were selected using the TEPITOPE algorithm, based on their predicted
      binding to HLA-DRB1*0405 and to the non-disease-related HLA-DRB1*15. RESULTS:
      HMCLL was recognized exclusively by the patients' PBMC (44%) but not by those of
      the control subjects (P < 0.01). PBMC from patients with VKH recognized an
      increased breadth of melanocyte-derived peptides at lower peptide concentrations
      than in the control subjects (68% vs. 25%; P < 0.01, at 1 microM) and did not
      produce the Th2 cytokine IL-4 in response to disease-specific peptides (0% vs.
      50%, P < 0.001). Five peptides were exclusively recognized in patients bearing
      HLA-DRB1*0405. Furthermore, HLA-DRB1*0405-bearing patients, but not those with
      HLA-DRB1*15, recognized an increased breadth of melanocyte epitopes in comparison
      to HLA-matched control subjects (60% vs. 28%; P < 0.05). CONCLUSIONS: These data
      indicate that patients with VKH are sensitized to melanocyte epitopes and display
      a peptide-specific Th1 cytokine response. In addition, the data indicate that
      patients bearing HLA-DRB1*0405 recognize a broader melanocyte-derived peptide
      repertoire, reinforcing the importance of this allele in susceptibility to the
      development of VKH disease.

PMID- 15980238
TI  - Failure of Acanthamoeba castellanii to produce intraocular infections.
AB  - PURPOSE: This study examined possible mechanisms to explain why Acanthamoeba
      castellanii remains restricted to the cornea and rarely produces intraocular
      infections. The first hypothesis proposed that trophozoites cannot penetrate
      Descemet's membrane and the corneal endothelium to enter the anterior chamber
      (AC). The second hypothesis proposed that the trophozoites can enter the AC;
      however, the aqueous humor (AH) contains factors that either induce encystment or
      kill the amoebae. METHODS: Descemet's membrane was isolated from pig corneas and
      was used to determine whether Acanthamoeba trophozoites could penetrate this
      membrane in vitro. In addition, the capacity of trophozoites to survive in AH was
      determined in vitro. Trophozoites (10(6)) were injected into the AC of hamster
      eyes, and the number of amoebae in the AC was determined by histopathology 1 to
      15 days later. RESULTS: The amoebae penetrated Descemet's membrane within 24
      hours of in vitro culture. Penetration was prevented by addition of serine
      protease inhibitors or a chicken monoclonal antibody against the Acanthamoeba
      serine protease MIP-133. Although AH induced encystment of the amoebae, cysts
      remained viable. Injection of amoebae into the AC induced a robust neutrophil
      infiltrate, which was associated with complete clearance by day 15 after AC
      injection. CONCLUSIONS: The findings suggest that A. castellanii is capable of
      penetrating Descemet's membrane and entering the AC. However, a robust neutrophil
      response is associated with the disappearance of intraocular trophozoites and
      suggests that cells of the innate immune apparatus are important in preventing
      Acanthamoeba keratitis from progressing to become an intraocular infection.

PMID- 15980239
TI  - Fas ligand but not complement is critical for control of experimental
      Staphylococcus aureus Endophthalmitis.
AB  - PURPOSE: To determine the role of complement and Fas Ligand (FasL) in the host
      defense against Staphylococcus aureus endophthalmitis. METHODS: C3-/-, FasL
      defective gld, and C57/BL6 (wild-type [WT]) mice were infected intravitreally
      with 500 and 5000 CFU S. aureus, and the course of infection was followed by
      determining the intraocular bacteria counts, retinal function by ERG, and
      morphologic damage and inflammation by histopathology and flow cytometry.
      RESULTS: In WT eyes injected with 500 CFU, S. aureus grew to 1 x 10(7) CFU/mL by
      24 hours, but was cleared by 96 hours. In the WT eyes injected with 5000 CFU, S.
      aureus grew to 2 x 10(9) CFU/mL by 72 hours, resulting in corneal perforation. C3
      /- eyes injected with 500 CFU reached transiently higher levels than their WT
      counterparts (P < 0.001), but eventually followed a similar course. Bacterial
      counts in gld eyes infected with 500 CFU were similar to those in WT eyes
      infected with 5000 CFU. In WT and C3-/- eyes injected with 500 CFU, retinal
      function decreased only transiently and recovered to 66% in 72 hours. In WT eyes
      injected with 5000 CFU and gld eyes infected with 500 CFU, retinal function was
      completely lost by 24 hours. By 24 hours, WT and C3-/- eyes injected with 500 CFU
      were infiltrated with a similar number of granulocytes, but recruitment was
      significantly impaired in gld eyes (P < 0.005). Cell counts in WT and C3-/- eyes
      decreased thereafter without overt retinal disease. In eyes injected with 5000
      CFU and gld eyes infected with 500 CFU, inflammatory cells completely filled the
      intraocular space by 48 hours. Retinal and uveal tissue was destroyed by that
      time. CONCLUSIONS: The tipping point for a good versus a bad outcome in this
      murine model of endophthalmitis lies between 500 and 5000 CFU S. aureus. This
      point is identical in animals deficient in complement activation, suggesting that
      complement does not play a significant role in the ocular defense against
      intraocular bacteria. In contrast, FasL was found to be critical for clearance,
      since animals deficient in FasL signaling were unable to control infection with
      500 CFU.

PMID- 15980240
TI  - Leukocyte diapedesis in vivo induces transient loss of tight junction protein at
      the blood-retina barrier.
AB  - PURPOSE: Although much is now understood about the molecular structure of tight
      junctions (TJs), little is known about the regulation of their function during
      neural inflammatory disease processes in vivo. The mechanisms by which leukocytes
      transmigrate the blood-retina barrier (BRB) without affecting endothelial
      permeability are controversial. METHODS: Confocal immunofluorescence microscopy
      of ex vivo retinal wholemounts was used to study BRB integrity during leukocyte
      adhesion and migration during experimental autoimmune uveoretinitis (EAU).
      Western blot analysis was used to measure levels of TJ proteins in EAU retina and
      RPE and in normal retina or RPE cultured with cytokines or chemokines. RESULTS:
      No evidence for discontinuity or other weakness of the endothelial or epithelial
      barrier at tricellular corners was observed, and maximum disruption of TJ protein
      expression was focused in retinal venules correlating with sites of leukocyte
      extravasation. Areas of maximum TJ protein loss in vivo also correlated with
      redistribution or loss of ensheathing astrocyte processes on venules but not
      adjacent capillaries or arterioles. Exposure of normal choroidal and retinal
      explants ex vivo to cytokines and chemokines alone did not downregulate total
      occludin-1 or claudin-3 TJ protein expression. CONCLUSIONS: The data presented
      herein support an active role for leukocytes in TJ disruption and blood-retina
      barrier (BRB) breakdown during retinal inflammation and further implicate venule
      microenvironment as a key factor in leukocyte recruitment to retinal tissue in
      vivo.

PMID- 15980241
TI  - A novel treatment for ocular tumors using membrane FasL vesicles to activate
      innate immunity and terminate immune privilege.
AB  - PURPOSE: Ocular immune privilege promotes tumor growth by hindering the
      development of innate and adaptive immunity. A prior study showed that ocular
      tumors expressing the membrane-only form of Fas ligand (FasL) terminate immune
      privilege, induce vigorous inflammation, undergo rejection, and induce systemic
      protective immunity. In these previous experiments the tumor cells used were
      genetically engineered to express membrane FasL. As an initial step toward
      developing an immunotherapy for intraocular tumors, the present study was
      conducted to examine whether injection of microvesicles expressing membrane FasL
      into ocular tumors (that are FasL negative) would have a similar effect. METHODS:
      Microvesicles expressing either no FasL or membrane-only Fas ligand were
      coinjected with L5178Y-R lymphoma cells into the anterior chambers (AC) of DBA/2
      mice. RESULTS: Tumor cells coinjected with control vesicles grew progressively in
      the AC, and all mice died of metastatic disease by day 15. By contrast, a single
      injection of membrane FasL vesicles induced a potent inflammatory response
      characterized by GR1+ neutrophils and F4/80+ macrophages and significantly
      improved survival from 0% in untreated mice to 58% in mFasL-treated mice. Among
      the surviving mice, the ocular tumor was eliminated in 55%, and the mice
      exhibited systemic protection from a second tumor challenge. In the remaining
      45%, the ocular tumor was not eliminated, but the mice were protected from liver
      metastases. CONCLUSIONS: Bioactive membrane FasL microvesicles coinjected with
      tumor cells induce a potent inflammatory response that terminates immune
      privilege, eliminates ocular tumors, and prevents metastatic disease.

PMID- 15980242
TI  - hTERT extends proliferative lifespan and prevents oxidative stress-induced
      apoptosis in human lens epithelial cells.
AB  - PURPOSE: Telomerase is a specialized polymerase that catalyzes synthesis of
      telomeres in most eukaryotes. When introduced into somatic cells, it extends the
      proliferative lifespan and prevents replicative senescence. Whether it has
      similar functions in lens epithelial cells, especially in human lens epithelial
      cells (HLECs) remains to be determined. In this study, the human telomerase
      reverse transcriptase (hTERT) catalytic subunit was introduced into HLECs. A
      stable cell line expressing hTERT was established and the functions of hTERT were
      studied. METHODS: The telomeric repeat amplification protocol (TRAP) assay was
      used to analyze the telomerase activity. Western blot analysis was used to
      examine hTERT expression. Southern blot analysis was used to detect telomere
      length. HLECs isolated from intact lenses were cultured in DMEM and transfected
      with hTERT cDNA. The expression of the exogenous hTERT was examined with RT-PCR,
      Western blot analysis, and TRAP assay. The functions of hTERT were examined with
      various techniques. RESULTS: Among the human, bovine, and rabbit lenses examined,
      only the central epithelium from the 6-month rabbit lens displayed telomerase
      activity. In both transparent and cataractous human lenses, hTERT activity and
      expression were not detected. However, the template RNA was present in both types
      of human lenses. The telomeres in transparent lenses were approximately 1 kb
      longer than those in cataractous lenses. The primary cultures and later passages
      of HLECs also displayed no detectable telomerase activity. Introduction of
      hTERTcDNA into HLECs followed by G418 selection yielded a stable line of HLECs
      expressing hTERT. In this line, hTERT has supported normal growth after 48
      population doublings (PDs) to date and also enhanced antiapoptotic activity
      against oxidative stress. CONCLUSIONS: Telomere lengths may be associated with
      cataractogenesis. hTERT introduced into HLECs prevents replicative senescence
      through telomere synthesis. Furthermore, hTERT displays functions beyond telomere
      synthesis in normal HLECs.

PMID- 15980243
TI  - Effect of oxidized betaB3-crystallin peptide on lens betaL-crystallin:
      interaction with betaB2-crystallin.
AB  - PURPOSE: To investigate the interaction of oxidized betaB3-crystallin peptide
      (residues 152-166) with betaL-crystallin and to identify peptide-interaction
      sites. METHODS: Peptides were oxidized by using CuSO4 and H2O2. Aggregation and
      light-scattering assays of bovine betaL-crystallin were conducted at 55 degrees C
      and 37 degrees C, respectively. Assays were performed in the presence of oxidized
      and nonoxidized betaB3-crystallin peptides and in the presence of alpha
      crystallin. Peptide-induced change in hydrophobicity was determined by bis-ANS
      (4,4'-dianilino-1,1' binaphthyl-5,5' disulfonic acid) binding study. Oxidized
      betaB3-peptide binding sites were identified by sulfo-SBED (sulfosuccinimidyl-2
      [6-(biotinamido)-2-{p-azidobenzamido}-hexanoamido] ethyl-1-3 dithiopropionate)
      labeling and mass spectrometric analysis. RESULTS: Aggregation and relative light
      scattering of betaL-crystallin was higher in the presence of oxidized betaB3
      crystallin peptide than with betaL-crystallin, without oxidized peptide and with
      nonoxidized peptide. Enhanced aggregation was observed despite the presence of
      alpha-crystallin in the assay. Furthermore, a significant increase in aggregation
      and light-scattering was observed in the presence of oxidized betaB3-peptide at
      37 degrees C. Bis-ANS binding to betaL-crystallin treated with oxidized betaB3
      peptide was two to three times higher than in the controls at 37 degrees C. The
      oxidized betaB3-peptide preferentially interacted with betaB2-crystallin. The
      data were confirmed by mass spectrometric analysis. CONCLUSIONS: Oxidized betaB3
      peptide interacts with betaB2-crystallin and enhances its aggregation and
      precipitation. Peptide-induced aggregation and increased hydrophobicity of the
      lens crystallin at 37 degrees C are relevant to crystallin aggregation in the
      aging lenses.

PMID- 15980244
TI  - L-type amino acid transporter 1-mediated L-leucine transport at the inner blood
      retinal barrier.
AB  - PURPOSE: L-type amino acid transporters (LATs) prefer branched-chain and aromatic
      amino acids, including neurotransmitter precursors. The objective of this study
      was to clarify the expression and function of LAT at the inner blood-retinal
      barrier (BRB). METHODS: [3H]L-Leucine transport at the inner BRB was
      characterized by using in vivo integration plot analysis and a conditionally
      immortalized rat retinal capillary endothelial cell line (TR-iBRB2). The
      expression of the LAT1 was demonstrated by quantitative real-time RT-PCR,
      immunoblot, and immunohistochemical analyses. RESULTS: The apparent influx
      permeability clearance of [3H]L-leucine in the rat retina was found to be 203
      microL/(min.g retina), supporting a carrier-mediated influx transport of L
      leucine at the BRB. [3H]L-Leucine uptake by TR-iBRB2 cells was an Na+-independent
      and concentration-dependent process with a Km of 14.1 microM. This process was
      more potently cis inhibited by substrates of LAT1, D-leucine, D-phenylalanine,
      and D-methionine, than those of LAT2, L-alanine, and L-glutamine. [3H]L-Leucine
      efflux from TR-iBRB2 cells was trans-stimulated by substrates of LAT1. The
      expression of LAT1 mRNA was 100- and 15-fold greater than that of LAT2 in TR
      iBRB2 and magnetically isolated rat retinal vascular endothelial cells,
      respectively. The expression of LAT1 protein was observed in TR-iBRB2 and primary
      cultured human retinal endothelial cells and immunostaining of LAT1 was observed
      along the rat retinal capillaries. CONCLUSIONS: LAT1 is expressed at the inner
      BRB and mediates blood-to-retina L-leucine transport. This transport system plays
      a key role in maintaining large neutral amino acids as well as neurotransmitters
      in the neural retina.

PMID- 15980245
TI  - Chemical toxicity of indocyanine green damages retinal pigment epithelium.
AB  - PURPOSE: To investigate the chemical toxicity of indocyanine green (ICG).
      METHODS: Surface active and precipitating effects of ICG were quantitatively
      analyzed by determining bovine serum albumin dissolved or precipitated in the
      presence or absence of salt solutions. The effects of precipitation on serum and
      cytotoxicity were evaluated by measuring the viability of retinal pigment
      epithelium (RPE) in vitro. RESULTS: ICG functioned as a surfactant without salts,
      but with nearly physiological concentrations of balanced salts, it functioned as
      a unique precipitating factor. This rendered the soluble molecules in serum that
      are indispensable in the culture of RPE cells insoluble during a 12-hour
      exposure, resulting in poor cell survival in vitro. Cytotoxicity in serum-free
      medium was also shown during brief exposures. CONCLUSIONS: Commonly used dosages
      of ICG directly applied into the vitreous cavity, which not only contact the
      retina but also invade the space between the retina and RPE through a macular
      hole, may be sufficient to induce retinal disorders after the damaging chemical
      property of ICG has disturbed the microenvironment.

PMID- 15980247
TI  - Grafting of ARPE-19 and Schwann cells to the subretinal space in RCS rats.
AB  - PURPOSE: To study the distribution of the human retinal pigment epithelium (hRPE)
      cell line ARPE-19 and human Schwann (hSC) cells grafted to the subretinal space
      of the Royal College of Surgeon (RCS) rat and the relation of graft cell
      distribution to photoreceptor rescue. METHODS: Cell suspensions of both donor
      types were injected into the subretinal space of 3-week-old dystrophic RCS rats
      through a transscleral approach, human fibroblast and medium were used as control
      grafts. All animals were maintained on oral cyclosporine. At 1, 2, 4, 6, 15, 28,
      and 36 weeks after grafting, animals were killed. Human cell-specific markers
      were used to localize donor cells. RESULTS: Both donor cell types, as revealed by
      antibodies survived for a substantial time. Their distribution was very
      different: hRPE cells formed a large clump early on and, with time, spread along
      the host RPE in a layer one to two cells deep, whereas hSCs formed many smaller
      clumps, mainly in the subretinal space. Both cells rescued photoreceptors beyond
      the area of donor cell distribution. The number of surviving cells declined with
      time. CONCLUSIONS: Both hRPE and hSC grafts can survive and rescue photoreceptors
      for a substantial time after grafting. The number of both donor cell types
      declined with time, which could be an immune-related problem and/or due to other
      factors intrinsic to the host RCS retina. The fact that rescue occurred beyond
      the area of donor cell distribution suggests that diffusible factors are
      involved, raising the possibility that the two cell types function in a similar
      manner to rescue photoreceptors.

PMID- 15980248
TI  - Thrombin inhibitor reduces leukocyte-endothelial cell interactions and vascular
      leakage after scatter laser photocoagulation.
AB  - PURPOSE: Macular edema is one of the most serious adverse effects after retinal
      scatter laser photocoagulation. It has been suggested that the inflammatory
      reaction after photocoagulation may be involved in the pathogenesis of macular
      edema. This study was designed to evaluate quantitatively the inhibitory effects
      of argatroban, a direct thrombin inhibitor, on leukocyte-endothelial cell
      interactions and vascular permeability after scatter laser photocoagulation.
      METHODS: Argon laser photocoagulation was performed in one half of the retina in
      pigmented male rats (n = 114). Argatroban was administered just before scatter
      laser photocoagulation. In the other half of the retina, AO leukocyte
      fluorography was used to evaluate in vivo leukocyte rolling along the retinal
      vein and accumulation in the retinal capillary bed. The expressions of P-selectin
      and intercellular adhesion molecule (ICAM)-1 were evaluated by reverse
      transcription-polymerase chain reaction. Retinal vessel permeability was
      quantified by using fluorescein isothiocyanate (FITC)-conjugated dextran.
      RESULTS: Scatter laser photocoagulation caused significant inflammatory leukocyte
      endothelial cell interactions in the nonphotocoagulated half of the retina.
      Treatment with argatroban suppressed leukocyte-endothelial cell interactions. The
      maximum number of rolling and accumulating leukocytes was reduced by 46.6% (P <
      0.01) and 51.4% (P < 0.01), respectively. The expression of P-selectin and ICAM-1
      mRNA was suppressed significantly in the argatroban-treated retinas (P < 0.05).
      Retinal vascular permeability was also suppressed significantly (P < 0.05).
      CONCLUSIONS: Argatroban suppressed leukocyte-endothelial cell interactions and
      blood-retinal barrier breakdown after scatter laser photocoagulation, suggesting
      that argatroban prevents postlaser macular edema.

PMID- 15980246
TI  - Loss of circadian photoentrainment and abnormal retinal electrophysiology in
      Math5 mutant mice.
AB  - PURPOSE: To determine how the absence of retinal ganglion cells (RGCs) in Math5
      (Atoh7) mutant mice affects circadian behavior and retinal function. METHODS: The
      wheel-running behavior of wild-type and Math5 mutant mice was measured under
      various light-dark cycle conditions. To evaluate retinal input to the
      suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were
      labeled in vivo. To assess changes in retinal function, corneal flash
      electroretinograms (ERGs) from mutant and wild-type mice were compared under dark
      and light-adapted conditions. Alterations in retinal neuron populations were
      evaluated quantitatively and with cell-type-specific markers. RESULTS: The Math5
      null mice did not entrain to light and exhibited free-running circadian behavior
      with a mean period (23.6 +/- 0.15 hours) that was indistinguishable from that of
      wild-type mice (23.4 +/- 0.19 hours). The SCN showed no anterograde labeling with
      a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs
      recorded from mutant mice had diminished scotopic a- and b-wave and photopic b
      wave amplitudes. The scotopic b-wave was more severely affected than the a-wave.
      The oscillatory potentials (OPs) and scotopic threshold response (STR) were also
      reduced. Consistent with these ERG findings, a pan-specific reduction in the
      number of bipolar cells and a smaller relative decrease in the number of rods in
      mutant mice were observed. CONCLUSIONS: Math5-null mice are clock-blind and have
      no RGC projections to the SCN. RGCs are thus essential for photoentrainment in
      mice, but are not necessary for the development or intrinsic function of the SCN
      clock. RGCs are not required to generate any of the major ERG waveforms in mice,
      including the STR, which is produced by ganglion cells in some other species. The
      diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most
      likely caused by the decreased abundance of retinal interneurons.

PMID- 15980249
TI  - Antitumoral action of the neurokinin-1-receptor antagonist L-733,060 and
      mitogenic action of substance P on human retinoblastoma cell lines.
AB  - PURPOSE: Activation of the neurokinin-1 receptor is known to induce proliferation
      in tumor cells, but it is as yet unknown whether this applies to retinoblastoma.
      This was an in vitro study of the growth inhibitory capacity of the potent and
      long-acting neurokinin-1 receptor antagonist L-733,060, at concentrations ranging
      from 7.5 to 20 microM, against the human retinoblastoma line WERI-Rb-1 and from
      10 to 25 microM against the human retinoblastoma line Y-79. The ability of
      substance P (an neurokinin-1 stimulator) to activate the cell growth of these
      retinoblastoma cell lines was also determined. METHODS: A cell counter was used
      to determine the number of viable cells, followed by application of the
      tetrazolium compound WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4 nitrophenyl))-5-(2,4
      disulfophenyl)-2H-tetrazolium, monosodium salt, colorimetric method to evaluate
      cell viability in this cytotoxicity assay. RESULTS: Nanomolar concentrations of
      substance P increased the growth of both cell lines and micromolar concentrations
      of L-733,060 inhibited the growth of the two cell lines studied, with and without
      previous administration of substance P. L-733,060 inhibited the growth of the
      WERI-Rb-1 and Y-79 cell lines in a dose-dependent manner. IC50 was 12.15 microM
      for 49 hours for WERI-Rb1 and 17.38 microM for 40 hours for Y-79. CONCLUSIONS:
      The findings demonstrate that substance P is a mitogen and also indicate that the
      neurokinin-1 receptor antagonist L-733,060 acts on both human retinoblastoma cell
      lines as an antitumoral agent.

PMID- 15980250
TI  - Dietary ganglioside and long-chain polyunsaturated fatty acids increase
      ganglioside GD3 content and alter the phospholipid profile in neonatal rat
      retina.
AB  - PURPOSE: During early development, the ganglioside composition of the retina
      changes significantly, in that GD3 becomes the primary ganglioside in the
      mammalian retina. Because gangliosides play an important role in neuronal cell
      differentiation and proliferation, this change in ganglioside profile may
      indicate retinal maturation. Dietary long-chain polyunsaturated fatty acids
      (LCPs) such as 20:4n-6 and 22:6n-3 improve visual acuity in infants. Dietary LCPs
      stimulate neonatal retinal development by altering membrane phospholipids, which
      in turn affect cell signaling pathways. It is unknown whether dietary ganglioside
      and LCPs affect the metabolism of phospholipids and gangliosides during retinal
      development. METHODS: Male Sprague-Dawley rats (18 days old) were fed
      semipurified diets consisting of 20% fat (control diet) for 2 weeks containing
      either 0.1% ganglioside enriched in GD3 (GG diet) or 1% 20:4n-6 and 0.5% 22:6n-3
      (LCP diet) in the control diet. The profile of ganglioside and phospholipid was
      measured. RESULTS: The GG diet increased the ganglioside content by 39% in the
      retina, with a relative increase in GD3 (by 13%). Dietary LCPs significantly
      increased the relative levels of GD3 (by 19%, P < 0.01). Total phospholipid was
      decreased by the LCP-supplemented diet (by 28%). Phosphatidylcholine and
      phosphatidylserine increased with concomitant decreases in phosphatidylinositol
      and lyso-phosphatidylethanolamine when animals were fed either the LCP or the GG
      diet. CONCLUSIONS: Animals fed dietary ganglioside increased in total retinal
      ganglioside and GD3 content during retinal development, with a concomitant
      alteration of phospholipid metabolism. Feeding animals dietary LCPs also affected
      ganglioside metabolism in the developing retina, suggesting a new mechanism by
      which these dietary lipids may promote maturation of photoreceptor cells.

PMID- 15980251
TI  - Lipoprotein-like particles and cholesteryl esters in human Bruch's membrane:
      initial characterization.
AB  - PURPOSE: To isolate and characterize cholesteryl ester-containing, lipoprotein
      like particles (LLPs) from normal aged human Bruch's membrane (BrM)/choroid (Ch).
      METHODS: From BrM/Ch of 20 eyes of 10 donors aged >60 years, LLPs were released
      by high-salt buffer, fractionated by density gradient ultracentrifugation, and
      characterized by determining cholesterol, triglyceride, and phospholipid
      concentration (by enzymatic colorimetry and fluorometry); cholesteryl ester
      composition (by electrospray ionization mass spectrometry, ESI/MS); and particle
      morphology (by negative stain electron microscopy). Apolipoprotein (apo) gene
      expression was determined with RT-PCR, Western blot analysis, and
      immunofluorescence of retinal-choroidal cryosections. In paraformaldehyde
      preserved eyes (20 eyes of 20 donors), cholesteryl ester composition of BrM/Ch,
      cornea, and sclera was determined by ESI/MS. RESULTS: A pooled fraction of LLP
      released from BrM/Ch (concentrated total LLP, density [d] < 1.24 g/mL fraction)
      was fractionated into two peaks. A large Peak 1 (with plasma LDL-HDL density
      range), containing predominantly phospholipid and unesterified cholesterol, was
      morphologically heterogeneous. A small Peak 2 (with plasma VLDL density range),
      enriched with esterified cholesterol, contained approximately 100 nm diameter
      round electron-lucent particles. Both peaks contained apoB and apoA-I, RPE and
      retina contained apoA-I mRNA transcripts, and BrM and drusen contained apoA-I
      immunoreactivity. Peaks 1 and 2, native RPE, and fresh BrM/Ch were cholesteryl
      linoleate enriched and contained little cholesteryl docosahexaenoate. Preserved
      BrM/Ch was cholesteryl oleate-enriched, unlike sclera and cornea. CONCLUSIONS:
      BrM/Ch LLP do not resemble plasma lipoproteins in density profile, cholesterol
      distribution, or morphology. Peak 2 contains EC-rich LLP resembling BrM particles
      in situ. BrM/Ch cholesteryl esters respond to long-term storage differently than
      esters of plasma lipoprotein origin accumulated in other ocular tissues. Evidence
      of intraocular apoB and apoA-I expression supports an emerging hypothesis that
      the RPE assembles and secretes a large, possibly novel, lipoprotein particle.

PMID- 15980252
TI  - Laser induces apoptosis and ceramide production in human retinal pigment
      epithelial cells.
AB  - PURPOSE: To investigate the cellular mechanisms involved in the cell death of
      human retinal pigment epithelial (hRPE) cells after their exposure to laser
      injury. METHODS: Cultured human hRPE cells were irradiated for different lengths
      of time and at different levels of energy using diode laser photocoagulation
      coupled with an intraocular laser probe. Apoptosis was determined by TUNEL
      staining and annexin-V labeling of phosphatidylserine exposure. Ceramide levels
      were quantified by the diacylglycerol kinase assay using thin-layer
      chromatography. RESULTS: Laser irradiation caused areas of apoptosis in the hRPE
      cells. These areas were detected around the ablated and necrotic laser scar and
      developed several hours after the laser irradiation. Laser irradiation
      concomitantly induced an increase in the intracellular production of ceramide, a
      lipid second messenger. CONCLUSIONS: The results demonstrate that laser
      irradiation induces apoptosis in hRPE cells and suggest that the underlying
      signaling mechanism involves ceramide generation.

PMID- 15980253
TI  - Ischemia-reperfusion causes exudative detachment of the rabbit retina.
AB  - PURPOSE: To characterize the activation of macroglial (Muller) and microglial
      cells, as well as neuronal cell degeneration, during ischemia-reperfusion in
      rabbit retina and to test the possible effect of triamcinolone acetonide on
      gliosis. METHODS: Transient retinal ischemia was produced by increasing
      intraocular pressure for 60 minutes. Triamcinolone (8 mg) was intravitreally
      applied immediately after the cessation of ischemia. At 3 and 8 days after
      reperfusion, the K+ currents of acutely isolated Muller cells were recorded, and
      the Ca2+ responses of Muller cells on stimulation of P2Y receptors were recorded
      fluorometrically in retinal wholemounts. Microglial/immune cells in the nerve
      fiber layer of retinal wholemounts were labeled with isolectin. To evaluate
      neuronal and Muller cell loss, the numbers of cells were counted in retinal
      slices. RESULTS: Transient ischemia caused exudative detachment of the central
      retina that was characterized by disruption of the pigment epithelial monolayer,
      the presence of scattered pigment epithelial and immune cells in the expanded
      subretinal space, and retinal folds. A significant loss of photoreceptor cells
      was observed at 8 days after reperfusion. At 3 and 8 days after reperfusion,
      Muller cell gliosis was apparent, as indicated by cellular hypertrophy,
      downregulation of K+ channel expression, and an increased number of cells that
      displayed P2Y receptor-mediated Ca2+ responses. The number of microglial/immune
      cells increased strongly after reperfusion. Intravitreal triamcinolone did not
      affect the parameters of Muller cell gliosis but decreased the number of
      microglial/immune cells. CONCLUSIONS: Ischemia-reperfusion of the rabbit retina
      causes exudative retinal detachment that is characterized by a loss of
      photoreceptor cells, whereas the inner retina remains largely preserved. Micro-
      and macroglial cells are activated early during reperfusion, even before dropout
      of the photoreceptor cells. Intravitreal triamcinolone may decrease the degree of
      microglial/immune cell activation.

PMID- 15980255
TI  - Differential behavior of simple and complex cells in visual cortex during a brief
      IOP elevation.
AB  - PURPOSE: To study and compare responses of different types of cortical neurons in
      the primary visual cortex in cats to grating stimuli before and during brief
      elevation of intraocular pressure (IOP). METHODS: Single-unit
      electrophysiological recordings were performed in anesthetized and paralyzed
      cats. The IOP was elevated by injecting saline into the anterior chamber of the
      cat's eyes through a syringe needle. The IOP was elevated to a level at which the
      retinal perfusion pressure (arterial pressure minus IOP) was maintained at
      approximately 30 mmHg for a period of 4 minutes. The responses of simple and
      complex cells in the primary visual cortex to visually drifting sinusoidal
      gratings were measured before and during the elevation of IOP. RESULTS: The
      response amplitude of all the cortical cells in the primary visual cortex
      declined during a brief elevation of IOP. The decrease in the response of simple
      cells was always more significant than that of complex cells. The differential
      decrease between the two major types of cells was independent of the cell's
      receptive field location and cortical depth. There was a mild tendency for cells
      with higher preferred spatial frequencies to be more sensitive than those with
      lower frequencies. The preferred orientation and direction of most cortical cells
      remained roughly unchanged though their orientation and direction biases
      decreased. An increase in the animal's blood pressure, which returned the retinal
      perfusion pressure to a normal level, compensated for the decreased response
      induced by the elevation of IOP. CONCLUSIONS: The differential effects of a brief
      elevation of IOP on the response of simple and complex cells in the visual cortex
      are general and may originate from the retina through the lateral geniculate
      nucleus (LGN), where different effects of elevation of IOP are exerted on X- and
      Y-type retinal ganglion cells. The results may suggest differential behavior of
      neurons tin the parvo and magno pathways of the primate.

PMID- 15980254
TI  - Leukemia inhibitory factor blocks expression of Crx and Nrl transcription factors
      to inhibit photoreceptor differentiation.
AB  - PURPOSE: Activating ligands of gp130, including leukemia inhibitory factor (LIF),
      can block differentiation and function of retinal neurons. This study focused on
      determining whether LIF inhibits differentiation of photoreceptors by altering
      cell fate or by blocking the expression of essential transcription factors in
      vivo. METHODS: Transgenic mice were generated that had lens-specific expression
      of the secreted human LIF protein. Retinal differentiation was assessed by
      histology and by gene expression analysis, with in situ hybridization,
      immunohistochemistry, and real-time qRT-PCR. Electroretinograms were used to
      assess retinal function. RESULTS: LIF did not prevent or alter the timing of
      outer and inner nuclear layer separation, but it inhibited phototransduction gene
      expression in both rods and cones, thereby blocking functional maturation of
      photoreceptors. LIF also reduced the expression of Crx, Nrl, and Nr2e3, and
      upregulated the expression of transcription inhibitors Baf and Fiz1. CONCLUSIONS:
      LIF expression did not appear to alter photoreceptor cell fate specification, but
      it inhibited subsequent differentiation. These results suggest that gp130 ligands
      can inhibit photoreceptor functional differentiation by reducing Crx- and Nrl
      dependent transcription.

PMID- 15980256
TI  - The multifocal ERG in diabetic patients without retinopathy during euglycemic
      clamping.
AB  - PURPOSE: Prolonged multifocal electroretinogram (mfERG) implicit times have been
      observed in diabetes, although the acute response to hyperglycemia is an
      acceleration of the ERG. The hypothesis for the current investigation was that
      this discrepancy is caused by a protracted adaptational response of the retina to
      hyperglycemia. METHODS: Fourteen patients with type 1 diabetes without
      retinopathy were blood glucose clamped at 5 mM for 75 minutes before the
      recording of the mfERG. The results were compared with those found in 14 age
      matched healthy subjects. RESULTS: During acute normoglycemia, patients with type
      1 diabetes without retinopathy demonstrated an overall 1.36-ms delay of the P1
      first-order implicit times (P = 0.0013) and a 0.72-ms delay of the second-order
      P1 (P = 0.0049) compared with healthy subjects at 4.9 +/- 0.28 mM blood glucose.
      During acute hyperglycemia, the P1 first-order delay was only 0.81 ms (P = 0.02),
      and the P1 second-order implicit time was comparable to that of healthy subjects
      (P > 0.05). The magnitude of the diabetes-associated implicit time delay, at both
      levels of glycemia, was proportional to the level of chronic hyperglycemia at
      study entry, as expressed by the patients' HbA1c. CONCLUSIONS: During acute
      normoglycemia, patients with type 1 diabetes without retinopathy demonstrated a
      delayed mfERG response compared with the healthy subjects. The delay was more
      pronounced during euglycemia than during hyperglycemia, and at both levels of
      glycemia, the delay was proportional to the patients' habitual hyperglycemia. The
      results show that chronic hyperglycemia induces an adaptational response that
      tends to normalize retinal implicit times at a higher level of habitual glycemia.

PMID- 15980257
TI  - The ciliary corona: physical model and simulation of the fine needles radiating
      from point light sources.
AB  - PURPOSE: Most people see, around bright lights against dark backgrounds, a
      radiating pattern of numerous fine, slightly colored needles of light-the so
      called ciliary corona. The purpose of this study was to try to explain this
      phenomenon. METHODS: Recently, it has been shown that light-scattering in the
      eye, measured psychophysically and on human donor lenses, can be explained
      assuming the presence of specific distributions of small particles in the eye.
      Light entering the eye is diffracted by these particles. Each such particle
      causes a circular diffraction pattern on the retina of tens of degrees, much like
      the well-known Airy pattern. The optics of combining many such diffraction
      patterns was modeled and the resultant pattern simulated graphically. The
      simulations were compared with observations on the ciliary corona, as seen by the
      natural eye. RESULTS: The diffraction discs originating from all the particles
      coherently superimposed on the retina. Because of phase differences this resulted
      in breaking the Airy-like discs into a fine spotted pattern when monochromatic
      light was used. For white (polychromatic) light, the spots line up to form the
      very fine-line pattern seen in the ciliary corona. Details such as the width and
      color of the needles follow from the theoretical treatment and were demonstrated
      by simulations. CONCLUSIONS: The details of the ciliary corona can be understood
      on the basis of polychromatic light-scattering by the particles predicted to be
      present in human eye lenses on the basis of light-scattering studies of donor
      lenses.

PMID- 15980258
TI  - Factors influencing reaction time during automated kinetic perimetry on the
      Tubingen computer campimeter.
AB  - PURPOSE: To determine the effect of age, examination, location, luminance,
      subject, and vigilance on reaction time (RT) in automated kinetic perimetry.
      METHODS: Thirty-six normal volunteers (20-70 years old) underwent kinetic
      campimetric examinations, during which RTs (time from appearance of a stimulus to
      response) were recorded. Stimuli with a diameter of 26 minutes of arc (Goldmann
      III) were presented on horizontal vectors with an angular velocity of 2 deg/s.
      Thirty-two positions in the 30 degrees radius visual field were tested six times,
      at luminance levels of 41.62 and 110 cd/m2 (background 10 cd/m2). An analysis of
      RT variance (ANCOVA) was performed. RESULTS: Median RT increased with age from
      370 ms (20-30-year-old subjects) to 440 ms (60-70-year-old subjects). There was a
      strong dependency of RT from the individual subjects examined (means range, 313
      411 ms), from the course of one examination period, from the examination and
      stimulus luminance, and from the location in the visual field. CONCLUSIONS:
      Reaction time during automated kinetic perimetry varies considerably. This study
      shows that the factors of age, the subject examined, his or her daily condition,
      the course within one examination period, and the stimulus location and luminance
      are of relevance. For a much more reliable prediction of individual RTs and thus
      a precise assessment of local kinetic thresholds, application of some additional
      kinetic stimuli (RT time vectors) within the intact visual field areas is
      necessary.

PMID- 15980259
TI  - D-GLYCERATE 3-KINASE, the last unknown enzyme in the photorespiratory cycle in
      Arabidopsis, belongs to a novel kinase family.
AB  - D-GLYCERATE 3-KINASE (GLYK; EC 2.7.1.31) catalyzes the concluding reaction of the
      photorespiratory C2 cycle, an indispensable ancillary metabolic pathway to the
      photosynthetic C3 cycle that enables land plants to grow in an oxygen-containing
      atmosphere. Except for GLYK, all other enzymes that contribute to the C2 cycle
      are known by their primary structures, and the encoding genes have been
      identified. We have purified and partially sequenced this yet missing enzyme from
      Arabidopsis thaliana and identified it as a putative kinase-annotated single-copy
      gene At1g80380. The exclusive catalytic properties of the gene product were
      confirmed after heterologous expression in Escherichia coli. Arabidopsis T-DNA
      insertional knockout mutants show no GLYK activity and are not viable in normal
      air; however, they grow under elevated CO2, providing direct evidence of the
      obligatory nature of the ultimate step of the C2 cycle. The newly identified GLYK
      is both structurally and phylogenetically distinct from known glycerate kinases
      from bacteria and animals. Orthologous enzymes are present in other plants,
      fungi, and some cyanobacteria. The metabolic context of GLYK activity in fungi
      and cyanobacteria remains to be investigated.

PMID- 15980260
TI  - SLOW WALKER1, essential for gametogenesis in Arabidopsis, encodes a WD40 protein
      involved in 18S ribosomal RNA biogenesis.
AB  - The progression of mitotic division cycles and synchronous development between
      and within the male and female reproductive organs are essential for plant sexual
      reproduction. Little is known about the genetic control of the progression of
      mitotic cycles of the haploid genome during gametogenesis in higher plants. Here,
      we report the phenotypic and molecular characterization of an Arabidopsis
      thaliana mutant, slow walker1 (swa1), in which the progression of the mitotic
      division cycles of the female gametophyte was disrupted. Confocal microscopy
      revealed that megagametophyte development was asynchronous in swa1, causing
      embryo sacs to arrest at two-, four-, or eight-nucleate stages within the same
      pistil. A delayed pollination experiment showed that a small fraction of the swa1
      embryo sacs were able to develop into functional female gametophytes. The swa1
      mutation also showed a slight reduction in penetrance through the male
      gametophyte, although the pollen grains were morphologically normal. Molecular
      analysis indicates that SWA1 encodes a protein with six WD40 repeats that is
      localized in the nucleolus in interphase cells. The SWA1 gene is expressed in
      cells undergoing active cell divisions, including functional megaspores and the
      female gametophytic cells. RNA interference results indicated that knockout of
      SWA1 inhibited root growth significantly and led to the accumulation of
      unprocessed 18S pre-rRNA. These data suggest that SWA1 most likely plays a role
      in rRNA biogenesis that is essential for the progression of the mitotic division
      cycles during gametogenesis in plants.

PMID- 15980261
TI  - A Link between ethylene and auxin uncovered by the characterization of two root
      specific ethylene-insensitive mutants in Arabidopsis.
AB  - The plant hormone ethylene participates in the regulation of a variety of
      developmental processes and serves as a key mediator of plant responses to biotic
      and abiotic stress factors. The diversity of ethylene functions is achieved, at
      least in part, by combinatorial interactions with other hormonal signals. Here,
      we show that ethylene-triggered inhibition of root growth, one of the classical
      effects of ethylene in Arabidopsis thaliana seedlings, is mediated by the action
      of the WEAK ETHYLENE INSENSITIVE2/ANTHRANILATE SYNTHASE alpha1 (WEI2/ASA1) and
      WEI7/ANTHRANILATE SYNTHASE beta1 (ASB1) genes that encode alpha- and beta
      subunits of a rate-limiting enzyme of Trp biosynthesis, anthranilate synthase.
      Upregulation of WEI2/ASA1 and WEI7/ASB1 by ethylene results in the accumulation
      of auxin in the tip of primary root, whereas loss-of-function mutations in these
      genes prevent the ethylene-mediated auxin increase. Furthermore, wei2 and wei7
      suppress the high-auxin phenotypes of superroot1 (sur1) and sur2, two auxin
      overproducing mutants, suggesting that the roles of WEI2 and WEI7 in the
      regulation of auxin biosynthesis are not restricted to the ethylene response.
      Together, these findings reveal that ASA1 and ASB1 are key elements in the
      regulation of auxin production and an unexpected node of interaction between
      ethylene responses and auxin biosynthesis in Arabidopsis. This study provides a
      mechanistic explanation for the root-specific ethylene insensitivity of wei2 and
      wei7, illustrating how interactions between hormones can be used to achieve
      response specificity.

PMID- 15980262
TI  - Seven Lotus japonicus genes required for transcriptional reprogramming of the
      root during fungal and bacterial symbiosis.
AB  - A combined genetic and transcriptome analysis was performed to study the
      molecular basis of the arbuscular mycorrhiza (AM) symbiosis. By testing the AM
      phenotype of nodulation-impaired mutants and complementation analysis, we defined
      seven Lotus japonicus common symbiosis genes (SYMRK, CASTOR, POLLUX, SYM3, SYM6,
      SYM15, and SYM24) that are required for both fungal and bacterial entry into root
      epidermal or cortical cells. To describe the phenotype of these mutants at the
      molecular level, we screened for differentiating transcriptional responses of
      mutant and wild-type roots by large-scale gene expression profiling using cDNA
      amplified fragment length polymorphism. Two percent of root transcripts was found
      to increase in abundance during AM development, from which a set of AM-regulated
      marker genes was established. A Ser-protease (SbtS) and a Cys-protease (CysS)
      were also activated during root nodule development. AM-induced transcriptional
      activation was abolished in roots carrying mutations in common symbiosis genes,
      suggesting a central position of these genes in a pathway leading to the
      transcriptional activation of downstream genes. By contrast, AM fungus-induced
      gene repression appeared to be unaffected in mutant backgrounds, which indicates
      the presence of additional independent signaling pathways.

PMID- 15980263
TI  - Regulation of WUSCHEL transcription in the stem cell niche of the Arabidopsis
      shoot meristem.
AB  - Pluripotent stem cells are localized in specialized microenvironments, called
      stem cell niches, where signals from surrounding cells maintain their
      undifferentiated status. In the Arabidopsis thaliana shoot meristem, the homeobox
      gene WUSCHEL (WUS) is expressed in the organizing center underneath the stem
      cells and integrates regulatory information from several pathways to define the
      boundaries of the stem cell niche. To investigate how these boundaries are
      precisely maintained within the proliferating cellular context of the shoot
      meristem, we analyzed the transcriptional control of the WUS gene. Our results
      show that the WUS promoter contains distinct regulatory regions that control
      tissue specificity and levels of transcription in a combinatorial manner.
      However, a 57-bp regulatory region is all that is required to control the
      boundaries of WUS transcription in the shoot meristem stem cell niche, and this
      activity can be further assigned to two adjacent short sequence motifs within
      this region. Our results indicate that the diverse regulatory pathways that
      control the stem cells in the shoot meristem converge at these two short sequence
      elements of the WUS promoter, suggesting that the integration of regulatory
      signals takes place at the level of a central transactivating complex.

PMID- 15980264
TI  - Identification of novel genes in Arabidopsis involved in secondary cell wall
      formation using expression profiling and reverse genetics.
AB  - Forward genetic screens have led to the isolation of several genes involved in
      secondary cell wall formation. A variety of evidence, however, suggests that the
      list of genes identified is not exhaustive. To address this problem, microarray
      data have been generated from tissue undergoing secondary cell wall formation and
      used to identify genes that exhibit a similar expression pattern to the secondary
      cell wall-specific cellulose synthase genes IRREGULAR XYLEM1 (IRX1) and IRX3.
      Cross-referencing this analysis with publicly available microarray data resulted
      in the selection of 16 genes for reverse genetic analysis. Lines containing an
      insertion in seven of these genes exhibited a clear irx phenotype characteristic
      of a secondary cell wall defect. Only one line, containing an insertion in a
      member of the COBRA gene family, exhibited a large decrease in cellulose content.
      Five of the genes identified as being essential for secondary cell wall
      biosynthesis have not been previously characterized. These genes are likely to
      define entirely novel processes in secondary cell wall formation and illustrate
      the success of combining expression data with reverse genetics to address gene
      function.

PMID- 15980265
TI  - Nonalcoholic fatty liver disease and atherosclerosis.

PMID- 15980266
TI  - Cardioprotective effects of high-density lipoproteins: the evidence strengthens.

PMID- 15980267
TI  - Return to ectopia: stem cells in the artery wall.

PMID- 15980268
TI  - Down but not out: new insights into the role of alphaVbeta3 integrins in vascular
      healing.

PMID- 15980269
TI  - Simvastatin given for 3 days can inhibit thrombin generation and activation of
      factor V and enhance factor Va inactivation in hypercholesterolemic patients.

PMID- 15980271
TI  - Proceedings from the workshop: Use of Nutrition in the Management and Treatment
      of Inflammatory Bowel Disease. October 28-29, 2004, Lausanne, Switzerland.

PMID- 15980270
TI  - Chi: a little sequence controls a big enzyme.

PMID- 15980272
TI  - Enteral nutrition in the management of Crohn's disease.
AB  - Exclusive feeding of defined formula diets has been used successfully as an
      alternative to corticosteroid treatment of active Crohn's disease, but the
      mechanism of efficacy remains conjectural. Recognition that polymorphisms in the
      NOD2/CARD15 gene confer susceptibility to Crohn's disease has increased
      appreciation of the interactions between the innate immune system and enteric
      bacteria, which lead to chronic intestinal inflammation. The 2 major goals of
      this workshop are: first, in light of current understanding of pathogenesis, to
      examine possible mechanisms of action of enteral nutrition as primary therapy;
      and second, to make evidence-based recommendations concerning its use in the new
      era of biologic therapies, when mucosal healing has become a realistic goal.
      Factors influencing efficacy, including duration, location of intestinal
      inflammation, and formula composition require consideration.

PMID- 15980273
TI  - Immunopathogenesis of Crohn's disease.
AB  - This review highlights the huge advances made in the understanding of Crohn's
      disease in the last 15 years. The pathogenic immune response in the gut wall is a
      highly polarised T helper cell type 1 response, probably directed against
      antigens of the commensal flora. There is marked over-expression of pro
      inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and increased
      production of matrix degrading enzymes by fibroblasts and macrophages, which are
      probably responsible for ulceration and fistula formation. Crohn's disease runs
      in families and the susceptibility genes identified so far are associated with
      innate recognition of microbial products (Nod2) or epithelial barrier function
      (OCTN cation transporter genes and DLG5). Endogenous healing pathways mediated by
      transforming growth factor (TGF)-beta1 are inhibited because mucosal inflammatory
      cells express Smad7, the endogenous intracellular inhibitor of TGF-beta
      signalling. This makes it unlikely that enteral feeds containing TFG-beta are
      therapeutic by means of direct anti-inflammatory effects, however TGF-beta may
      still be involved because it is a well known epithelial motogen and may promote
      mucosal healing, in synergy with changes in mucosal bacterial populations as a
      result of the change in the diet.

PMID- 15980274
TI  - Control of systemic and local inflammation with transforming growth factor beta
      containing formulas.
AB  - Enteral nutrition therapy with liquid diet has been shown to be effective in
      achieving clinical remission in intestinal Crohn's disease. The mechanism of
      action of this therapy, however, is still poorly understood. As part of our
      assessment of the action of 3 related polymeric enteral therapies, we have used a
      variety of techniques to document the histological and cytokine responses, in the
      mucosa and, systemically, to these treatments. The feeds studied (AL110, Modulen
      IBD and ACD004 [Nestle, Vevey, Switzerland]) all have casein as the protein
      source, are lactose free and are rich in transforming growth factor beta (TGF
      beta). They have all been shown to induce clinical remission associated with
      mucosal healing. In the case of Modulen IBD, as well as mucosal macroscopic and
      histological healing there was a fall in mucosal proinflammatory cytokines:
      interleukin-1 mRNA in colonic and ileal, interleukin-8 mRNA in the colon and
      interferon gamma mRNA in the ileum, but a rise in the regulatory cytokine TGF
      beta mRNA in the ileum. These results indicate that these formulas are
      influencing the disease process itself, and thus suggest that the clinical
      remission achieved is a result of a reduction in inflammation, rather than a
      consequence of some other nutrition effect.

PMID- 15980275
TI  - The anti-inflammatory effects of enteral nutrition.
AB  - Enteral nutrition has a positive effect on growth in children with active Crohn's
      disease. The question arises: is this is due only to improved nutrition? Enteral
      formulas may also directly reduce inflammation, lowering the expression of
      cytokines like interleukin (IL)-6 that inhibit growth. Four lines of evidence
      support the hypothesis that enteral formulas directly lessen inflammation:
      enteral nutrition directly affects the inflamed intestine; changes in
      inflammatory markers precede repletion of nutrition status; molecular pathways
      exist linking changes in luminal contents to the expression of class II MHC genes
      in intestinal epithelium in animal studies; and enteral formulas have a direct
      effect on cytokine expression by intestinal epithelial cells.

PMID- 15980276
TI  - Milk casein-based diet containing TGF-beta controls the inflammatory reaction in
      the HLA-B27 transgenic rat model.
AB  - BACKGROUND: A casein-based formula containing TGF-beta has been successfully used
      in adolescents during acute episodes of Crohn's disease. The role played by this
      molecule requires confirmation. We have examined the capacity of a TGF-beta
      containing diet to control the intestinal inflammation in HLA-B27 transgenic
      rats, and compared its effects with a similar diet devoid of TGF-beta. METHODS:
      Three groups of rats were studied. HLA-B27/hbeta2M transgenic rats were fed with
      a casein-based rat-adapted diet containing TGF-beta or a control casein-based
      diet without TGF-beta. Fischer control animals were fed the latter. Body weight,
      dietary intake, tissue weights, fecal samples, leukocyte counts, and acute phase
      response were analyzed. Intestinal inflammation was assessed by histology,
      myeloperoxidase, and mRNA expression of cytokines. MUC2 protein expression was
      assessed by immunohistochemistry. Breakdown of muscle protein was examined.
      RESULTS: The test diet improved diarrhea increasing the fecal dry matter and the
      colonic inflammation as shown by a lower inflammatory score (2.43 +/- 1.13 vs
      4.42 +/- 0.53, p < .05), lower mucosal thickness (431.25 +/- 72.29 vs 508.57 +/-
      81.32 microm, p = .08) and decreased IFNgamma mRNA expression. MUC2 protein
      expression was increased in HLA rats fed the TGF-beta diet compared with HLA rats
      fed the control diet, but restitution to normal pattern was not observed. The
      test diet also decreased leukocytosis and the acute phase response and improved
      the muscle catabolic response. CONCLUSION: The TGF-beta containing diet has a
      beneficial effect in an animal model of intestinal inflammation. Our observations
      support a potential role for dietary TGF-beta in the restoration of immune
      homeostasis.

PMID- 15980277
TI  - Enteral nutrition as primary therapy in childhood Crohn's disease: control of
      intestinal inflammation and anabolic response.
AB  - Crohn's disease in childhood is a chronic relapsing and remitting condition that
      can significantly impact normal growth and development. This influences choice of
      both initial and ongoing management. The goal of therapy is to induce and
      maintain remission with minimal side effects. Enteral nutrition is effective in
      active disease and will induce disease remission in most cases avoiding
      corticosteroid use. The high frequency of relapse means additional
      immunosuppressive therapies are usually required but nutrition remains a key
      priority as part of the subsequent management strategy.

PMID- 15980278
TI  - Synergy between immunosuppressive therapy and enteral nutrition in the management
      of childhood Crohn's disease.
AB  - Induction of a remission in children with Crohn's disease is increasingly
      successful. However this success is dependent on what measure we use to define
      "remission." Achieving a clinical remission is possible in >70% of children with
      Crohn's disease at diagnosis, while a mucosal or even immunological remission may
      occur in <50%. The importance of what ;degree of remission' should be achieved
      during maintenance therapy is discussed. Does early aggressive management with
      immunomodulators or biological agents indeed alter the natural history of the
      disease, and is it possible to give a prognosis based on either a snap-shot of
      endoscopic appearance, or a mucosal cytokine profile? The potential benefits of
      using a 6-8 week course of exclusive enteral nutrition as an induction therapy in
      combination with azathioprine/6-mercaptopurine are discussed. Whole protein
      formulae are safe and effective at achieving a clinical remission, however they
      are not a long-term maintenance strategy. Given the relative safety of these
      immunosuppressants and their efficacy in children treated at diagnosis, it is now
      more important than ever to predict which individuals will benefit from use of
      immunomodulators very early in the disease process. There is brief mention of
      enteral nutrition as maintenance therapy. Given the very limited data available,
      it is still not possible to recommend long-term nutrition supplementation as a
      maintenance therapy in all children. However, some children may respond to
      repeated shorter cycles of exclusive enteral nutrition in the absence of other
      therapeutic options.

PMID- 15980279
TI  - The use of enteral nutrition in the management of Crohn's disease in adults.
AB  - Crohn's disease is a chronic, relapsing disease and none of the treatments
      developed so far can cure it. Artificial nutrition is effective to both treat
      malnutrition when present and induce remission. However, striking advances in
      anti-inflammatory and immunomodulating therapies (including infliximab) and low
      compliance to treatment in the first trials have limited its place in the
      management of adults to drug-resistant patients. Randomized controlled trials
      show that artificial nutrition is effective in >50% of the cases in this selected
      population. Significant progress has recently been made to improve the
      palatability (and thus acceptability) of some enteral solutions, which can be
      consumed by the oral route and as pharmaconutrition. We reviewed the literature
      on enteral nutrition in adults with Crohn's disease. We present herein the
      results of the studies performed with antioxidants, glutamine, short-chain fatty
      acids, prebiotics, probiotics, low microparticle diets, and a TGFbeta2 enriched
      formulation.

PMID- 15980280
TI  - Enteral nutrition and microflora in pediatric Crohn's disease.
AB  - BACKGROUND: Exclusive enteral nutrition (EN) is an established primary therapy
      for pediatric Crohn's disease (CD). The mechanism of action of such treatment is
      still conjectural. The aim of the present study was to investigate if EN-induced
      remission is associated with modification of the fecal microflora in CD. METHODS:
      Stool samples were collected from 5 healthy children and adolescents over a
      period of 3 months, and from 9 children and adolescents with active CD. To induce
      disease remission, children with CD received a course of exclusive EN for 8 weeks
      with a polymeric formula (Modulen IBD, Nestle). At the end of the course of
      exclusive EN, children returned to a free diet but continued to take 40% of the
      daily caloric intake as polymeric formula. Fecal microflora was analyzed by 16S
      ribosomal DNA polymerase chain reaction and temperature gradient gel
      electrophoresis (TGGE) with direct visual comparison of band profiles of PCR
      products. RESULTS: In 8 of 9 children, the exclusive EN alone induced disease
      remission. In 1 child, it was necessary to add steroids to the exclusive EN
      course to achieve remission. In all children with CD, analysis of gel band
      distribution revealed profound modification of the fecal microflora after
      exclusive EN. Variations of band distribution corresponding to different
      bacterial species were observed also in children on partial EN and required time
      to achieve stability of the band profile. In contrast, control healthy children
      showed a host-specific and stable TGGE profile over time. CONCLUSION: These data
      suggest that a possible mechanism of action of EN in inducing disease remission
      in CD is the capacity of modification of gut microflora. Possible explanations of
      such capacity are both low residue and prebiotic properties of the polymeric
      liquid formula.

PMID- 15980281
TI  - Macronutrients and bioactive molecules: is there a specific role in the
      management of inflammatory bowel disease?
AB  - The effect of bioactive nutrient molecules on inflammatory response has an
      archetype in Inflammatory Bowel Disease. The exacerbated inflammatory response in
      such conditions can be nutritionally modified by 2 ways: changing the response of
      the host, or changing the composition of the intestinal ecosystem. Host response
      can be modified by changing the cell structure and function which is nutrient
      dependent. Nutrient deprivation will lead to a situation where there is not
      enough building material for cell replacement and the synthesis of mediators
      (enzymes, hormones, etc). However, this may occur even in a situation where there
      is no quantitative nutrient deprivation but only qualitative changes. In
      Inflammatory Bowel Disease, changes in the sources of some nutrients such as
      lipids or carbohydrates (CHO) can modify the inflammatory response. Lipids, by
      changing cell membrane composition, may modify the pattern of eicosanoid
      synthesis, intracellular signal transmission and activation of nuclear
      transcription factors, which modify the expression of some genes-that is,
      changing the host response. On the other hand, certain sources of carbohydrates,
      by undergoing anaerobic bacterial fermentation, drop the pH in the intestinal
      lumen favoring the growth of certain strains of bacteria which act favorably in
      maintaining tolerance in the bowel. In addition, as a consequence of CHO
      fermentation, short-chain fatty acids are produced which, especially butyrate,
      may act in 2 ways: by providing energy to the epithelial cells, but also as anti
      inflammatory substrate-that is, modifying at least 1 of the mechanisms triggering
      the inflammatory response enhancement. However, it should not be forgotten that
      the cellular response to dietary modifications will depend on the individual
      genome, as has been recently observed. This may explain why some individuals do
      and others do not show a similar response to dietary interventions.

PMID- 15980283
TI  - Ethnic variation in the impact of emotion and emotion regulation on health: a
      replication and extension.
AB  - Although emotions and patterns of emotion regulation are central to models
      linking personality and health, the generalizability of these models to diverse
      populations of older adults remains untested. In this study, 1,364 community
      dwelling women (aged 50-70 years) from six ethnic groups completed self-report
      measures of trait anger, inhibition, defensiveness, and health. As expected,
      reports of trait anger and emotion inhibition predicted poorer health (and
      defensiveness better health), even when demographics and health behaviors were
      controlled. However, these characteristics related to outcome differently across
      ethnic groups; greater anger was related to better health in all groups other
      than U.S-born European Americans, and increased emotion inhibition was associated
      with better health among immigrant Eastern European women. Results are discussed
      within a contextualistic model of emotions and health, and directions for future
      research are given.

PMID- 15980284
TI  - Aging and longitudinal change in perceptual-motor skill acquisition in healthy
      adults.
AB  - Knowledge about aging of perceptual-motor skills is based almost exclusively on
      cross-sectional studies. We examined age-related changes in the retention of
      mirror-tracing skills in healthy adults who practiced for 3 separate days at
      baseline and retrained 5 years later at follow-up. Overall, the speed and
      accuracy of an acquired skill were partially retained after a 5-year interim,
      although the same asymptote was reached. Analyses with individual learning curves
      indicated that the effects of age on mirror-tracing speed were greater at
      longitudinal follow-up than at baseline, with older adults requiring more
      training to reach asymptote. Thus, although the long-term retention of acquired
      skills declines with age, older adults still retain the ability to learn the
      skill. Moreover, those who maintained a processing speed comparable with that of
      the younger participants evidenced no age-related performance decrements on the
      mirror-drawing task.

PMID- 15980285
TI  - Sleep complaints, subjective and objective sleep patterns, health, psychological
      adjustment, and daytime functioning in community-dwelling older adults.
AB  - We examined sleep complaints, subjective and objective sleep patterns, health,
      psychological adjustment, and daytime functioning in 103 community-dwelling older
      adults to identify factors associated with sleep complaints. We collected 2 weeks
      of sleep diaries and actigraphy. Only health distinguished complaining from
      noncomplaining sleepers. Noncomplaining good sleepers had poorer objective sleep
      quantity than complaining poor sleepers. Actigraphy distinguished noncomplaining
      good and complaining poor sleepers only. Subjective and objective sleep
      quantities were related for noncomplainers only; this relationship was stronger
      for women. Implications include a need for research exploring: 1. sleep
      complaints, sleep perceptions, and health; 2. interventions focusing on older
      individuals with insomnia secondary to/comorbid with poor health; 3. gender
      differences in subjective sleep estimates and in "single-shot" versus
      longitudinal sleep measures.

PMID- 15980286
TI  - From caregiving to bereavement: trajectories of depressive symptoms among wife
      and daughter caregivers.
AB  - This study examined the trajectory of depressive symptoms for wife and daughter
      caregivers during the transition from caregiving to bereavement, and it
      investigated whether the trajectory varies by caregivers' caregiving stress,
      social support, and background characteristics. Hierarchical linear modeling was
      used to analyze four-wave longitudinal data collected from 157 wife and daughter
      caregivers who lost elderly relatives to death. Results show that, on average,
      caregivers experience increasing depressive symptoms as their care recipients
      approach death, and they experience decreasing symptoms after. Care recipients'
      problematic behavior and caregivers' kinship, income, and feelings of overload
      moderate the change in depressive symptoms during the transition. Services to
      support caregivers should target specific groups of caregivers, based on
      caregiving experience and background characteristics, at times when they are most
      in need.

PMID- 15980287
TI  - The interplay between life stressors and depressive symptoms among older adults.
AB  - This study examined mutual predictive associations between life stressors and
      depressive symptoms in later life. A sample of late-middle-aged and older adults
      (N = 1,291) was surveyed at baseline and 1 year, 4 years, and 10 years later. At
      each contact point, participants completed an inventory that assessed chronic and
      acute life stressors and depressive symptoms. Over the 10-year interval, there
      was evidence of both social causation and social selection processes: More life
      stressors were associated with subsequent increases in depressive symptoms
      (social causation), and more depressive symptoms were associated with subsequent
      increases in stressors (social selection or stress generation). These findings
      reflect a mutual influence process in which life stressors and depressive
      symptoms can alter each other.

PMID- 15980288
TI  - Does religiousness buffer against the fear of death and dying in late adulthood?
      Findings from a longitudinal study.
AB  - We used longitudinal data (N = 155) to investigate the relation between
      religiousness and fear of death and dying in late adulthood. We found no linear
      relations between religiousness and fear of death and dying. Individuals who were
      moderately religious feared death more than individuals who scored high or low on
      religiousness. Fear of death also characterized participants who lacked
      congruence between belief in an afterlife and religious practices. We replicated
      the curvilinear relation between fear of death and religiousness in late
      adulthood with religiousness in middle adulthood, controlling for
      sociodemographic variables, life satisfaction, social support, and stressors.
      Older participants (in their mid-70s) who experienced more bereavement and
      illness feared the dying process less than younger participants (in their late
      60s). The findings support the hypothesis that firmness and consistency of
      beliefs and practices, rather than religiousness per se, buffers against death
      anxiety in old age.

PMID- 15980289
TI  - Framing effects in younger and older adults.
AB  - A growing literature on decision making in older adults suggests that they are
      more likely to use heuristic processing than are younger adults. We assessed this
      tendency in the context of a framing effect, a decision-making phenomenon whereby
      the language used to describe options greatly influences the decision maker's
      choice. We compared decision making under a standard ("heuristic") condition and
      also under a "justification" condition known to reduce reliance on heuristics. In
      the standard condition, older adults were more susceptible than younger adults to
      framing but the two groups did not differ when participants were asked to provide
      a justification. Thus, although older adults may spontaneously rely more on
      heuristic processing than younger adults, they can be induced to take a more
      systematic approach to decision making.

PMID- 15980290
TI  - Exploring the connections: theory and research.

PMID- 15980291
TI  - Linking the two ends of life: what gerontology can learn from childhood studies.
AB  - This paper extends provocative ideas from the emerging interdisciplinary field of
      childhood studies to the field of gerontology. These ideas constitute a framework
      for building new kinds of theories and research on old people and old age
      gathered around rights and responsibilities of and for old people; focused on
      their agency and social participation; concerned with the social problems of old
      people, as well as how old people are constructed to be social problems; anchored
      in their perspectives and voices; dedicated to describing and explaining both
      commonness and difference in their experiences and statuses; devoted to
      understanding old people as beings and becomings; and attentive to the
      interdependence of generations within families and societies. These commitments
      will require gerontology to strengthen its treatment of sociocultural phenomena,
      prompt more genuinely interdisciplinary scholarship, and advocate a wider range
      of research methods and data. A "new social studies of old people and old age,"
      nurtured around these ideas, will also raise the visibility of old people and old
      age in science, public policy, and social life.

PMID- 15980292
TI  - Racial disparities in self-rated health at older ages: what difference does the
      neighborhood make?
AB  - OBJECTIVES: Racial differences in self-rated health at older ages are well
      documented. African Americans consistently report poorer health, even when
      education, income, and other health status indicators are controlled. The extent
      to which neighborhood-level characteristics mediate this association remains
      largely unexplored. We ask whether neighborhood social and economic resources
      help to explain the self-reported health differential between African Americans
      and Whites. METHODS: Using the 1990 Decennial Census, the 1994-1995 Project on
      Human Development in Chicago Neighborhoods-Community Survey, and selected years
      of the 1991-2000 Metropolitan Chicago Information Center-Metro Survey, we examine
      the impact of neighborhood structure and social organization on self-rated health
      for a sample of Chicago residents aged 55 and older (N = 636). We use multilevel
      modeling techniques to examine both individual and neighborhood-level covariates.
      RESULTS: Findings indicate that affluence, a neighborhood structural resource,
      contributes positively to self-rated health and attenuates the association
      between race and self-rated health. When the level of affluence in a community is
      low, residential stability is negatively related to health. Collective efficacy,
      a measure of neighborhood social resources, is not associated with health for
      this older population. DISCUSSION: Analyses incorporating individual and
      neighborhood-level contextual indicators may further our understanding of the
      complex association between sociodemographic factors and health.

PMID- 15980293
TI  - Invited commentary: subjective health and the dangers of absent individual
      effects and crude contextual proxies of causal mechanisms.

PMID- 15980295
TI  - How good is assisted living? Findings and implications from an outcomes study.
AB  - OBJECTIVES: The objective of this work was to determine 1-year medical outcomes,
      nursing home transfer, and functional change of assisted living (AL) residents
      and their relationship to care. METHODS: On-site interviews and observations
      regarding the status and care of 2,078 residents in 193 facilities across four
      states were conducted; follow-up was by telephone interview with care providers.
      RESULTS: Annual mortality and transfer rates were 14.4 and 21.3 per 100
      residents. The probability of hospitalization and new/worsening morbidities over
      a standardized quarter per 100 residents was 12.7 and 22.7. Standardized change
      in function was notable among those who were transferred or died and small among
      others. Facility characteristics did not generally relate to medical outcomes and
      transfer, and those that related to functional change were small and occurred
      across multiple functions. Facilities that are affiliated with another level of
      care were more likely to transfer; nurse staffing was favorable for
      hospitalization but not transfer; and aide turnover was protective for mortality.
      DISCUSSION: No single component defines "good" AL care. Predictors and outcomes
      are inconsistent, and effect sizes are small. Therefore, practice and policy
      should not focus narrowly on any one area or restrict the type of care-this being
      welcome news that supports diversity to accommodate individual preferences.

PMID- 15980296
TI  - Living quarters and unmet need for personal care assistance among adults with
      disabilities.
AB  - OBJECTIVES: This study used a person-environment (P-E) framework to examine
      individual capabilities and social and physical environmental attributes for
      their association with unmet assistance needs in activities of daily living
      (ADLs). Analyses were replicated among five ADLs (bathing, dressing,
      transferring, toileting, eating) and test the relative risk of apartment dwellers
      compared to those living in houses. METHODS: Data were obtained from the National
      Health Interview Survey, Supplement on Disability Followback Survey. Analyses
      consisted of a nationally representative sample of aged and nonaged adults with
      one or more ADL limitations. RESULTS: Slightly less than 1 in 5 subjects with a
      specific ADL limitation had unmet needs for that ADL. This was true across all
      ADLs. The likelihood of unmet ADL assistance increased with the number of ADL
      limitations and other health status indicators. It was at least 50% higher among
      those living in apartments than in houses and higher among Hispanics. There were
      no differences by age or gender. DISCUSSION: The P-E framework postulates that
      individuals seek settings matched to their capabilities, but findings suggest
      that many are at risk for adaptation at any one time. Specific risk factors are
      identified. Selection factors like preferences, expectations, and adaptation
      options available have not been directly measured.

PMID- 15980297
TI  - Resilience in the face of serious illness among chronically ill African Americans
      in later life.
AB  - OBJECTIVES: The purpose of this work was to examine older African Americans'
      philosophies about their chronic illnesses and how those philosophies affected
      chronic illness management. METHODS: Three to five in-depth interviews were
      conducted over the course of several years with 38 respondents between the ages
      of 65 and 91. Both open-ended and semistructured questions were asked. RESULTS:
      Respondents demonstrated determination, perseverance, and tenacity no matter how
      serious their illnesses were. Racism was instrumental in shaping the responses of
      these African Americans to their illnesses through cultural values that
      emphasized independence, spirituality, and survival. Respondents demonstrated a
      resilient philosophy as they faced disabling illness. DISCUSSION: This research
      attests to the importance of examining racism in the analysis of how older ethnic
      minorities live with chronic illness, as it provides the context for
      understanding the development of culturally specific philosophies about illness.
      Resilience, as a culturally specific philosophy, is an important adjunct to
      chronic illness management in later life, and more needs to be understood about
      the dimensions that shape it by cultural group.

PMID- 15980300
TI  - Henry Kandrup's ideas about relaxation of stellar systems.
AB  - Henry Kandrup wrote prolifically on the problem of relaxation of stellar systems.
      His picture of relaxation was significantly more refined than the standard
      description in terms of phase mixing and violent relaxation. In this article, I
      summarize Henry's work in this and related areas.

PMID- 15980298
TI  - How does self-assessed health change with age? A study of older adults in Japan.
AB  - OBJECTIVE: This research examines how the trajectories of self-rated health
      evolve among elderly Japanese individuals and how socioeconomic status (SES),
      social relations, and baseline health differentiate these trajectories. METHODS:
      Data came from a five-wave panel study of a national sample of 2,200 Japanese old
      adults between 1987 and 1999. Hierarchical linear models and cluster analysis
      were employed to depict major patterns of temporal changes in self-rated health.
      RESULT: Overall perceived health becomes worse, but only slightly, between ages
      60 and 85, whereas it appears to improve a little bit after age 85. Underlying
      the observed age norm are four subtrajectories including constant good health,
      early onset of perceived health decline, late onset of perceived health decline,
      and a course of recovery from poor self-assessed health. DISCUSSION: Diverse
      subjective health trajectories exist in old age, extending well into the 90s.
      Prior observations of the effects of SES, social relations, and baseline health
      on health states and transitions can now be extended to trajectories of
      subjective health. Our analysis of Japanese data provides important benchmarks
      for comparisons with observations made in other developed nations.

PMID- 15980301
TI  - Chaotic collisionless evolution in galaxies and charged-particle beams.
AB  - Both galaxies and charged particle beams can exhibit collisionless evolution on
      surprisingly short time scales. This can be attributed to the dynamics of chaotic
      orbits. The chaos is often triggered by resonance caused by time dependence in
      the bulk potential, which acts almost identically for attractive gravitational
      forces and repulsive electrostatic forces. The similarity suggests that many
      physical processes at work in galaxies, although inaccessible to direct
      controlled experiments, can be tested indirectly via controlled experiments with
      charged particle beams, such as those envisioned for the University of Maryland
      electron ring currently nearing completion.

PMID- 15980302
TI  - Chaotic dynamics in charged-particle beams: possible analogs of galactic
      evolution.
AB  - During the last couple of years of his life, Henry Kandrup became intensely
      interested in using charged-particle beams as a tool for exploring the dynamics
      of evolving galaxies. He and I recognized that both galaxies and charged-particle
      beams can exhibit collisionless relaxation on surprisingly short time scales, and
      that this circumstance can be attributed to phase mixing of chaotic orbits. The
      chaos is often triggered by resonances caused by time dependence in the bulk
      potential, which acts almost identically for attractive gravitational forces as
      for repulsive electrostatic forces superposed on external focusing forces.
      Together we published several papers concerning evolving beams and galaxies,
      papers that relate to diverse topics such as the physics of chaotic mixing, the
      applicability of the Vlasov-Poisson formalism, and the production of diffuse
      halos. We also teamed with people from the University of Maryland to begin
      designing controlled experiments to be done at the University of Maryland
      electron ring. This paper highlights our collaborative findings as well as plans
      for future investigations that the findings have motivated.

PMID- 15980303
TI  - The University of Maryland electron ring: a platform for study of galactic
      dynamics on a laboratory scale.
AB  - The University of Maryland electron ring (UMER) is a novel experimental storage
      ring designed to investigate the dynamics of large systems of collisionless
      particles that nevertheless interact via collective mechanisms. Heavily diagnosed
      and designed to circulate a 100 mA electron beam at 10 keV for several turns,
      UMER allows us to follow the evolution of the beam over a large number of
      dynamical periods. Given the similarity of dynamics between the Coulomb forces
      and gravitational forces, it is possible to design beam experiments that will
      simulate such astrophysical events as galactic merger, for instance. The cross
      comparison of beam experiments with accelerator simulation codes provides
      invaluable benchmarks of transient processes akin to, for example, violent
      relaxation in stellar systems that are otherwise impossible to obtain.

PMID- 15980304
TI  - Wavelet-based Poisson solver for use in particle-in-cell simulations.
AB  - We report on a successful implementation of a wavelet-based Poisson solver for
      use in three-dimensional particle-in-cell simulations. Our method harnesses
      advantages afforded by the wavelet formulation, such as sparsity of operators and
      data sets, existence of effective preconditioners, and the ability simultaneously
      to remove numerical noise and additional compression of relevant data sets. We
      present and discuss preliminary results relating to the application of the new
      solver to test problems in accelerator physics and astrophysics.

PMID- 15980305
TI  - Energy trapping in loaded string models with long- and short-range couplings.
AB  - This paper illustrates the possibility, in simple loaded string models, of
      trapping most of the system energy in a single degree of freedom for very long
      times, demonstrating in particular that the robustness of the trapping is
      enhanced by increasing the connectance of the system, that is, the extent to
      which many degrees of freedom are coupled directly by the interaction Hamiltonian
      and/or the strength of the couplings.

PMID- 15980306
TI  - Characterization of chaos: a new, fast, and effective measure.
AB  - A new technique for characterization of the regular or chaotic nature of
      dynamical orbits has been discovered. It takes advantage of morphological and
      dynamical properties of orbits, and is very effective, at least for time
      independent systems with two degrees of freedom. The new technique was initially
      designed with time-dependent and N-body systems in mind. For this reason one of
      its main goals is to provide straightforward information about the transient
      chaos associated with such regimes. Equally important is the distinction it can
      provide between sticky and wildly chaotic epochs during the evolution of chaotic
      orbits. The most important advantage over the existing methods is that it can
      characterize an orbit using a very small number of orbital periods. For these
      reasons the new method is extremely promising to be useful and effective in a
      broad spectrum of disciplines.

PMID- 15980307
TI  - Hard sphere dynamics for normal and granular fluids.
AB  - A fluid of N smooth, hard spheres is considered as a model for normal (elastic
      collision) and granular (inelastic collision) fluids. The potential energy is
      discontinuous for hard spheres so that the pairwise forces are singular and the
      usual forms of Newtonian and Hamiltonian mechanics do not apply. Nevertheless,
      particle trajectories in the N particle phase space are well defined and the
      generators for these trajectories can be identified. The first part of this
      presentation is a review of the generators for the dynamics of observables and
      probability densities. The new results presented in the second part refer to
      applications of these generators to the Liouville dynamics for granular fluids. A
      set of eigenvalues and eigenfunctions of the generator for this Liouville
      dynamics system is identified in a special stationary representation. This
      provides a class of exact solutions to the Liouville equation that are closely
      related to hydrodynamics for granular fluids.

PMID- 15980308
TI  - Nonlinear stability of Newtonian galaxies and stars from a mathematical
      perspective.
AB  - The stability of equilibrium configurations of galaxies or stars are time honored
      problems in astrophysics. We present mathematical results on these problems that
      have recently been obtained by Yan Guo and the author in the context of the
      Vlasov-Poisson and the Euler-Poisson models. Based on a careful analysis of the
      minimization properties of conserved quantities--the total energy and so called
      Casimir functionals--nonlinear stability results are obtained for a wide class of
      equilibria.

PMID- 15980309
TI  - Chaos in orbits due to disk crossings.
AB  - We study orbits of halo stars in simple models of galaxies with disks and halos
      to see if the cumulative effects of the sudden changes in acceleration that occur
      at disk crossings can induce chaos. We find that they can, although not in all
      orbits and not in all potentials. Most of the orbits that become chaotic stay
      relatively close to the disk and range widely in the radial direction. Heavier
      disks and increased halo flattening both enhance the extent of the chaos. A
      limited range of experiments with a three-component model of the Milky Way with
      an added central bulge finds that many chaotic disk-crossing orbits can be
      expected in the central regions, and that prolateness of the halo is much more
      effective than oblateness in generating chaos.

PMID- 15980310
TI  - Systems with escapes.
AB  - There are two types of escapes in conservative dynamical systems with two degrees
      of freedom: escapes to infinity and escapes to certain singular points at a
      finite distance. In both cases the areas on a surface of section are not
      preserved. We consider the basins of escape to infinity in simple Hamiltonian
      systems. The initial conditions of orbits escaping after 1, 2, ... intersections
      with a surface of section form in general spiral fractal sets. Then we consider
      the sets of escapes into two fixed black holes for various values of the energy.
      The forms of these sets depend on the unstable periodic orbits and their
      asymptotic curves. We find the characteristics of the simple periodic orbits and
      their changes for various values of the energy.

PMID- 15980311
TI  - On bars and haloes: their interaction and their orbital structure.
AB  - A live halo plays an active role in the formation and evolution of bars by
      participating in the angular momentum redistribution that drives the dynamical
      evolution. Angular momentum is emitted mainly by near-resonant material in the
      bar region and is absorbed mainly by near-resonant material in the halo and in
      the outer disc. This exchange determines the strength of the bar, the decrease in
      its pattern speed, as well as its morphology. Thus, contrary to previous beliefs,
      a halo can help the bar grow, so that bars growing in galaxies with responsive
      massive haloes can become stronger than bars growing in disc dominated galaxies.
      During the evolution the halo does not stay axisymmetric. It forms a bar that is
      shorter and fatter than the disc bar and stays so throughout the simulation,
      although its length grows considerably with time. I discuss the orbital structure
      in the disc and the halo and compare it with periodic orbits in analytical barred
      galaxy potentials. A central mass concentration (e.g., a central black hole or a
      central disc) weakens a bar and increases its pattern speed. The effect of the
      central mass concentration depends strongly on the model, being less strong in
      models with a massive concentrated halo and a strong bar.

PMID- 15980312
TI  - The basic dynamical mechanism in spiral galaxies.
AB  - This paper explicates the most fundamental mechanism that rules spiral galaxies.
      Although spiral galaxies are complex systems for which we do not yet have a
      complete understanding, the dark matter being the most severe unknown, it is
      possible to pinpoint the few physical factors that determine their most important
      properties, such as bars and spiral arms. Dynamics linked to the dissipative
      nature of gas and its transformation into stars provides clues that spiral
      galaxies are driven by dissipation close to a state of marginal stability with
      respect to the dynamics in the galaxy plane. Here, we present numerical evidence
      suggesting that warps play a similar role but in the transverse direction. N-body
      simulations show that typical galactic disks are also marginally stable with
      respect to a bending instability, leading to typical observed warps. The frequent
      occurrence of warps and asymmetries in the outer galactic disks, like bars in the
      inner disks, give new constraints on the dark matter, but this time in the outer
      disks.

PMID- 15980313
TI  - The two pattern speeds of NGC 3359.
AB  - Using both observations and theoretical techniques, we show that the barred
      spiral galaxy NGC 3359 contains two pattern speeds. The faster pattern speed for
      the bar is obtained from isophotal analysis and stellar orbit theory. To explain
      the spiral arms and the observed velocity field of the disk, a slower pattern
      speed is required. Nonlinear resonance coupling is the supporting theory for the
      existence of two pattern speeds for the galaxy. The best match of our models with
      the observed data indicates a pattern speed for the bar of 39.17 km.sec(-1)
      approximately kpc(-1) and a value between 10 and 16 km.sec(-1).kpc(-1) for the
      spiral.

PMID- 15980314
TI  - Evolution of binary supermassive black holes via chain regularization.
AB  - A chain regularization method is combined with special purpose computer hardware
      to study the evolution of massive black hole binaries at the centers of galaxies.
      Preliminary results with up to N = 0.26 x 10(6) particles are presented. The
      decay rate of the binary is shown to decrease with increasing N, as expected on
      the basis of theoretical arguments. The eccentricity of the binary remains small.

PMID- 15980315
TI  - Gravitomagnetic field and Penrose scattering processes.
AB  - In this paper we present theoretical model calculations involving Monte Carlo
      computer simulations of Compton scattering and electron-positron (e-e+) pair
      production processes in the ergosphere of a supermassive rotating black hole.
      Particles from an accretion disk surrounding the rotating black hole fall into
      the ergosphere and are scattered by particles that are confined in equatorial and
      nonequatorial orbits. The energy-momentum vectors are calculated for the
      scattered escaping particles. Particles escape with energies of about 3 GeV or
      greater. Importantly, these model calculations show that the Lense-Thirring
      effect, that is, the dragging of local inertial frames into rotation, inside the
      ergosphere, caused by the angular momentum of the rotating black hole, results in
      a gravitomagnetic force being exerted on the scattered escaping particles.
      Effects of this force on the Penrose scattered particles are analyzed and
      discussed.

PMID- 15980316
TI  - Self-gravity driven instabilities at accelerated interfaces.
AB  - Nonlinear hydrodynamic flows are ubiquitous in the interstellar medium (ISM).
      Such flows play an important role in shaping atomic and molecular clouds and
      determining the initial conditions for star formation. One mechanism by which
      nonlinear flows arise is the onset and growth of interfacial instabilities. Any
      interface of discontinuous density is subject to a host of instabilities,
      including Rayleigh-Taylor, Kelvin-Helmholtz, and Richtmyer-Meshkov. As part of an
      ongoing study of structure formation in the ISM, Hunter, Whitaker, and Lovelace
      discovered an additional density interface instability. This instability is
      driven by self-gravity and termed the self-gravity interfacial instability (SGI).
      The SGI causes any displacement of the interface to grow on roughly a free-fall
      time scale, even when the perturbation wavelength is much less than the Jeans
      length. Numerical simulations have confirmed the expectations of linear theory,
      including the near scale invariance of the growth rate. Here, we build upon
      previous work by considering an initial condition in which the acceleration due
      to self-gravity is non-zero at the interface.

PMID- 15980317
TI  - Dynamics of intracluster gas and bulk motions in clusters.
AB  - In this paper I briefly discuss progress in recent lines of research on the
      internal dynamics of clusters of galaxies that have been made possible thanks to
      improvements in current X-ray spectrometers that enable them to perform detailed
      spatially resolved spectroscopy. In particular, I focus on the study of bulk
      motion in intracluster gas and the nature of features called cold fronts.

PMID- 15980318
TI  - Resonance bands and binary-star formation.
AB  - Numerical computations on the evolution of realistically stratified, asymmetric,
      self-gravitating masses reveal the onset of an instability that is suggestive of,
      but not decisive for, the formation of a binary star. On the other hand, analysis
      of the evolution and stability of idealized models consisting of uniform-density
      ellipsoids has been qualitatively accurate in predicting certain features of the
      behavior of the more realistically stratified figures. This idealized theory is,
      therefore, reconsidered in an attempt to isolate additional qualitative features
      that may be common both to the idealized and to realistic figures, and therefore,
      serve not only as a guide in formulating issues to be addressed in numerical
      computations but also as a means of interpreting the outcomes of such
      calculations. Several such features are isolated in this paper, the most striking
      of which is the existence and importance of resonance bands of instability
      encountered by the evolutionary trajectories.

PMID- 15980319
TI  - The symplectic group and classical mechanics.
AB  - The symplectic group is the underlying symmetry group for Hamiltonian dynamics.
      Yet relatively little is commonly known about its properties including its Lie
      structure and representations. This paper describes and summarizes some of these
      properties; and, as a first application of symplectic group theory, provides a
      symplectic classification of all first-order differential equations in an even
      number of variables.

PMID- 15980320
TI  - Chaos and quantum mechanics.
AB  - The relationship between chaos and quantum mechanics has been somewhat uneasy-
      even stormy, in the minds of some people. However, much of the confusion may stem
      from inappropriate comparisons using formal analyses. In contrast, our starting
      point here is that a complete dynamical description requires a full understanding
      of the evolution of measured systems, necessary to explain actual experimental
      results. This is of course true, both classically and quantum mechanically.
      Because the evolution of the physical state is now conditioned on measurement
      results, the dynamics of such systems is intrinsically nonlinear even at the
      level of distribution functions. Due to this feature, the physically more
      complete treatment reveals the existence of dynamical regimes--such as chaos-
      that have no direct counterpart in the linear (unobserved) case. Moreover, this
      treatment allows for understanding how an effective classical behavior can result
      from the dynamics of an observed quantum system, both at the level of
      trajectories as well as distribution functions. Finally, we have the striking
      prediction that time-series from measured quantum systems can be chaotic far from
      the classical regime, with Lyapunov exponents differing from their classical
      values. These predictions can be tested in next-generation experiments.

PMID- 15980322
TI  - Insertions in the human immunodeficiency virus type 1 protease and reverse
      transcriptase genes: clinical impact and molecular mechanisms.

PMID- 15980323
TI  - Different anti-Candida activities of two human lactoferrin-derived peptides,
      Lfpep and kaliocin-1.
AB  - The synthetic peptides Lfpep and kaliocin-1 include the sequences from positions
      18 to 40 and 153 to 183 of human lactoferrin, respectively. Lfpep is a cationic
      peptide with bactericidal and giardicidal effects, whereas kaliocin-1 is a novel
      bactericidal peptide that corresponds to a highly homologous sequence present in
      the transferrin family of proteins. Both peptides presented fungicidal activity
      against Candida spp., including fluconazole- and amphotericin B-resistant
      clinical isolates. Lfpep exhibited higher antifungal activity (8- to 30-fold) and
      salt resistance than kaliocin-1. The killing activity of Lfpep was mediated by
      its permeabilizing activity on Candida albicans cells, whereas kaliocin-1 was
      unable to disrupt the cytoplasmic membrane, as indicated by its inability to
      allow permeation of propidium iodide and the small amount of K+ released. The
      amino acid sequence of kaliocin-1 includes the "multidimensional antimicrobial
      signature" conserved in disulfide-containing antimicrobial peptides and a
      striking similarity to brevinin-1Sa, an antimicrobial peptide from frog skin
      secretions, exhibiting a "Rana box"-like sequence. These features may be of
      interest in the design of new antifungals.

PMID- 15980324
TI  - Pharmacology and pharmacokinetics of the antiviral agent beta-D-2',3'-dideoxy-3'
      oxa-5-fluorocytidine in cells and rhesus monkeys.
AB  - Beta-D-2',3'-dideoxy-3'-oxa-5-fluorocytidine (D-FDOC) is an effective inhibitor
      of human immunodeficiency virus 1 (HIV-1) and HIV-2, simian immunodeficiency
      virus, and hepatitis B virus (HBV) in vitro. The purpose of this study was to
      evaluate the intracellular metabolism of d-FDOC in human hepatoma (HepG2), human
      T-cell lymphoma (CEM), and primary human peripheral blood mononuclear (PBM) cells
      by using tritiated compound. By 24 h, the levels of D-FDOC-triphosphate (D-FDOC
      TP) were 2.8 +/- 0.4, 6.7 +/- 2.3, and 2.0 +/- 0.1 pmol/10(6) cells in HepG2,
      CEM, and primary human PBM cells, respectively. Intracellular D-FDOC-TP
      concentrations remained greater than the 50% inhibitory concentration for HIV-1
      reverse transcriptase for up to 24 h after removal of the drug from cell
      cultures. In addition to d-FDOC-monophosphate (D-FDOC-MP), -diphosphate (D-FDOC
      DP), and -TP, D-FDOC-DP-ethanolamine and d-FDOC-DP-choline were detected in all
      cell extracts as major intracellular metabolites. D-FDOC was not a substrate for
      Escherichia coli thymidine phosphorylase. No toxicity was observed in mice given
      D-FDOC intraperitoneally for 6 days up to a dose of 100 mg/kg per day.
      Pharmacokinetic studies in rhesus monkeys indicated that D-FDOC has a t(1/2) of
      2.1 h in plasma and an oral bioavailability of 38%. The nucleoside was excreted
      unchanged primary in the urine, and no metabolites were detected in plasma or
      urine. These results suggest that further safety and pharmacological studies are
      warranted to assess the potential of this nucleoside for the treatment of HIV-
      and HBV-infected individuals.

PMID- 15980325
TI  - Proteus mirabilis bloodstream infections: risk factors and treatment outcome
      related to the expression of extended-spectrum beta-lactamases.
AB  - Bloodstream infection (BSI) due to Proteus mirabilis strains is a relatively
      uncommon clinical entity, and its significance has received little attention.
      This study was initiated to evaluate risk factors and treatment outcome of BSI
      episodes due to P. mirabilis producing extended-spectrum beta-lactamases (ESBLs).
      Twenty-five BSI episodes caused by P. mirabilis occurred at our hospital
      (Ospedale di Circolo e Fondazione Macchi, Varese, Italy) over a 7.5-year period.
      Phenotypic and molecular methods were used to assess ESBL production. Clinical
      records of BSI patients were examined retrospectively. Demographic data,
      underlying diseases (according to McCabe and Jackson classification and Charlson
      weighted index), risk factors, and treatment outcome were investigated by
      comparing cases due to ESBL-positive strains to cases due to ESBL-negative
      strains. Eleven isolates were found to express ESBLs (TEM-52 or TEM-92). The
      remaining 14 isolates were ESBL negative and were uniformly susceptible to
      extended-spectrum cephalosporins and monobactams. Comparison of the two groups
      showed that previous hospitalization in a nursing home (P = 0.04) and use of
      bladder catheter (P = 0.01) were significant risk factors for infections due to
      ESBL-positive strains. In addition, cases due to ESBL-positive strains showed a
      significantly higher mortality attributable to BSI (P = 0.04). BSI cases due to
      ESBL-negative isolates uniformly responded to therapy, whereas 5/11 cases due to
      ESBL-positive isolates failed to respond (P < 0.01). Use of carbapenems was
      associated with complete response independently of ESBL production. Therapeutic
      failure and mortality may occur in BSI episodes caused by ESBL-positive P.
      mirabilis isolates. Thus, recognition of ESBL-positive strains appears to be
      critical for the clinical management of patients with systemic P. mirabilis
      infections.

PMID- 15980326
TI  - Sequential actions of the two component peptides of the lantibiotic lacticin 3147
      explain its antimicrobial activity at nanomolar concentrations.
AB  - Lacticin 3147 is a two-peptide (LtnA1 and LtnA2) lantibiotic produced by
      Lactococcus lactis subsp. lactis DPC3147 and has inhibitory activity against all
      gram-positive microorganisms tested. In this study the specific activities of the
      component peptides (alone or in combination) were determined by using L. lactis
      subsp. cremoris HP as the target strain. Lacticin 3147 exhibited an MIC50 of 7 nM
      for each component peptide (in combination), suggesting a peptide stoichiometry
      of 1:1. Interestingly, the LtnA1 peptide demonstrated independent inhibitory
      activity, with an MIC50 of 200 nM against L. lactis HP. In parallel studies, the
      single peptide bacteriocin nisin exhibited an MIC50 of 50 nM against the same
      target strain. Sequential peptide addition (with an intermediate washing step)
      demonstrated that LtnA1 must be added before LtnA2 rather than vice versa to
      observe inhibitory activity. The nanomolar activity of the lacticin peptides
      suggests the involvement of a docking molecule, speculated to be lipid II. Taken
      together with the recently determined structure of lacticin 3147 (N. I. Martin,
      T. Sprules, M. R. Carpenter, P. D. Cotter, C. Hill, R. P. Ross, and J. C.
      Vederas, Biochemistry, 43:3049-3056, 2004), these data support the hypothesis
      that the mode of action for lacticin 3147 involves a lipid II binding step (by
      the mersacidin-like LtnA1 peptide, which would explain its independent inhibitory
      activity), followed by insertion of the more linear LtnA2 peptide into the target
      membrane, resulting in pore formation and ultimate cell death.

PMID- 15980327
TI  - Microplate Alamar blue assay for Staphylococcus epidermidis biofilm
      susceptibility testing.
AB  - Biofilms are at the root of many infections largely because they are much more
      antibiotic resistant than their planktonic counterparts. Antibiotics that target
      the biofilm phenotype are desperately needed, but there is still no standard
      method to assess biofilm drug susceptibility. Staphylococcus epidermidis ATCC
      35984 biofilms treated with eight different approved antibiotics and five
      different experimental compounds were exposed to the oxidation reduction
      indicator Alamar blue for 60 min, and reduction relative to untreated controls
      was determined visually and spectrophotometrically. The minimum biofilm
      inhibitory concentration was defined as < or = 50% reduction and a purplish well
      60 min after the addition of Alamar blue. All of the approved antibiotics had
      biofilm MICs (MBICs) of >512 microg/ml (most >4,096 microg/ml), and four of the
      experimental compounds had MBICs of < or = 128 microg/ml. The experimental
      aaptamine derivative hystatin 3 was used to correlate Alamar blue reduction with
      2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)
      reduction and viable counts (CFU/ml) for S. epidermidis ATCC 35984, ATCC 12228,
      and two clinical isolates. For all four strains, Alamar blue results correlated
      well with XTT (r = 0.83 to 0.97) and with CFU/ml results (r = 0.85 to 0.94).
      Alamar blue's stability and lack of toxicity allowed CFU/ml to be determined from
      the same wells as Alamar blue absorbances. If the described method of microplate
      Alamar blue biofilm susceptibility testing, which is simple, reproducible, cost
      effective, nontoxic, and amenable to high throughput, is applicable to other
      important biofilm forming species, it should greatly facilitate the discovery of
      biofilm specific agents.

PMID- 15980328
TI  - Emergence of a novel mutation in the FLLA region of hepatitis B virus during
      lamivudine therapy.
AB  - The emergence of resistance to lamivudine has been one of the major stumbling
      blocks to successful treatment and control of hepatitis B virus (HBV) infections.
      The major mechanism of resistance has been attributed to the alteration in the
      YMDD motif of the HBV polymerase due to an amino acid change of rtM204 to V/I and
      an accompanying rtL180M conversion. A novel mutation pattern in a patient having
      clinical breakthrough under lamivudine therapy was discovered. The mutant had a
      rtL180C/M204I genotype and was detected after 2 years of therapy with lamivudine.
      To characterize this novel variant, site-directed mutagenesis was performed using
      a vector construct containing the HBV genome. Transient transfection studies in
      human hepatoma cells with HBV carrying the new mutant demonstrated that the
      rtL180C/M204I mutant was resistant to lamivudine up to 10 microM. The resistance
      profile was comparable to that of the previously reported rtL180 M/M204I
      containing virus. These observations were further confirmed by generation of
      stable cultures transfected with the mutant virus.

PMID- 15980329
TI  - Putative VanRS-like two-component regulatory system associated with the inducible
      glycopeptide resistance cluster of Paenibacillus popilliae.
AB  - Paenibacillus popilliae contains vanF encoding a putative D-Ala:D-lactate (D-Lac)
      ligase, VanF, as part of the vanY(F)Z(F)H(F)FX(F) cluster that is similar in
      structure to the enterococcal vanA and vanB clusters. Using growth curves, we
      demonstrated that vancomycin resistance in P. popilliae is inducible. Using
      degenerate oligonucleotides targeted at bacterial cell wall ligases, we
      identified a second ligase gene with features of a D-Ala:D-Ala ligase in both P.
      popilliae and the related, vancomycin-susceptible, Paenibacillus lentimorbus. The
      3,380-bp region upstream of vanY(F)Z(F)H(F)FX(F) in P. popilliae ATCC 14706 was
      sequenced and found to contain genes encoding a putative two-component regulator,
      VanR(F)S(F), similar to VanRS but more closely related to a family of two
      component regulators linked to VanY-like carboxypeptidases in several
      glycopeptide-susceptible Bacillus species. This upstream region also included a
      transposase similar to a transposase found in Bacillus halodurans and, in some
      strains, a 99-bp insertion of unknown function with 95% nucleotide identity to a
      portion of the Tn1546 transposase gene. Analysis of glycopeptide resistance
      associated clusters from soil and/or insect-dwelling organisms may provide
      important clues to the molecular evolution of acquired glycopeptide resistance
      elements in human pathogens.

PMID- 15980330
TI  - Biological activity of an intravenous preparation of human vaccinia immune
      globulin in mouse models of vaccinia virus infection.
AB  - The biological activity of a new intravenous (i.v.) preparation of human vaccinia
      immune globulin (VIGIV) was evaluated in two mouse models of vaccinia virus (VV)
      infection. In a mouse tail lesion model, female CD-1 mice were inoculated i.v.
      with 7 x 10(4) PFU of VV to produce >10 lesions per tail 8 days later. In a mouse
      lethality model, female severe combined immunodeficient (SCID) mice were
      inoculated i.v. with 3 x 10(4) PFU of VV to produce 100% mortality within 45
      days. The ability of VIGIV to reduce tail lesion formation in CD-1 mice and
      mortality in SCID mice was determined by (i) pretreatment of a lethal VV dose
      with VIGIV prior to i.v. inoculation into SCID mice and (ii) i.v. administration
      of VIGIV to CD-1 and SCID mice the day before and up to 8 days after VV
      infection. VIGIV reduced the proportion of CD-1 mice with >10 tail lesions in a
      dose-related manner when VIGIV was given 1 day before and up to 1 day after VV
      inoculation. The pretreatment of VV with VIGIV prolonged survival and decreased
      mortality. VIGIV (100 and 400 mg/kg) prolonged survival when given up to 4 days
      after VV inoculation, and the 400-mg/kg dose reduced the mortality rate by 80%
      when given the day before or immediately after VV inoculation. The biological
      activity of VIGIV was demonstrated in both the immunocompetent and
      immunocompromised murine models. The timing of treatment relative to VV
      inoculation appeared to be important for the demonstration of VIGIV's biological
      activity.

PMID- 15980331
TI  - Antistaphylococcal effect related to the area under the curve/MIC ratio in an in
      vitro dynamic model: predicted breakpoints versus clinically achievable values
      for seven fluoroquinolones.
AB  - Prediction of the relative efficacies of different fluoroquinolones is often
      based on the ratios of the clinically achievable area under the concentration
      time curve (AUC) to the MIC, usually with incorporation of the MIC50 or the MIC90
      and with the assumption of antibiotic-independent patterns of the AUC/MIC
      response relationships. To ascertain whether this assumption is correct, the
      pharmacodynamics of seven pharmacokinetically different quinolones against two
      clinical isolates of Staphylococcus aureus were studied by using an in vitro
      model. Two differentially susceptible clinical isolates of S. aureus were exposed
      to two 12-h doses of ciprofloxacin (CIP) and one dose of gatifloxacin (GAT),
      gemifloxacin (GEM), grepafloxacin (GRX), levofloxacin (LVX), moxifloxacin (MXF),
      and trovafloxacin (TVA) over similar AUC/MIC ranges from 58 to 932 h. A specific
      bacterial strain-independent AUC/MIC relationship with the antimicrobial effect
      (I(E)) was associated with each quinolone. Based on the I(E)-log AUC/MIC
      relationships, breakpoints (BPs) that are equivalent to a CIP AUC/MIC ratio of
      125 h were predicted for GRX, MXF, and TVA (75 to 78 h), GAT and GEM (95 to 103
      h) and LVX (115 h). With GRX and LVX, the predicted BPs were close to those
      established in clinical settings (no clinical data on other quinolones are
      available in the literature). To determine if the predicted AUC/MIC BPs are
      achievable at clinical doses, i.e., at the therapeutic AUCs (AUC(ther)s), the
      AUC(ther)/MIC50 ratios were studied. These ratios exceeded the BPs for GAT, GEM,
      GRX, MXF, TVA, and LVX (750 mg) but not for CIP and LVX (500 mg). AUC/MIC ratios
      above the BPs can be considered of therapeutic potential for the quinolones. The
      highest ratios of AUC(ther)/MIC50 to BP were achieved with TVA, MXF, and GEM (2.5
      to 3.0); intermediate ratios (1.5 to 1.6) were achieved with GAT and GRX; and
      minimal ratios (0.3 to 1.2) were achieved with CIP and LVX.

PMID- 15980332
TI  - The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase
      counteracts enhanced excision of zidovudine monophosphate associated with
      thymidine analog resistance mutations.
AB  - Thymidine analog mutations (TAMs) in human immunodeficiency virus type 1 (HIV-1)
      reverse transcriptase (RT) confer resistance to zidovudine (AZT) by increasing
      the rate of ATP-dependent phosphorolysis of the terminal nucleotide monophosphate
      (primer unblocking). By contrast, the L74V mutation, which confers resistance to
      didanosine, sensitizes HIV-1 to AZT and partially restores AZT susceptibility
      when present together with one or more TAMs. To compare rates of primer
      unblocking in RTs carrying different clusters of TAMs and to explore the
      biochemical mechanism by which L74V affects AZT susceptibility, ATP-mediated
      rescue of AZT-blocked DNA synthesis was assayed using a series of purified
      recombinant RTs. Rates of primer unblocking were higher in the 67N/70R/219Q RT
      than in the 41L/210W/215Y enzyme and were similar to rates observed with an RT
      carrying six TAMs (41L/67N/70R/210W/215Y/219Q). The presence of 74V in an
      otherwise wild-type RT reduced the rate of primer unblocking to a degree similar
      to that observed with the M184V mutation for lamivudine resistance, which also
      sensitizes HIV-1 to AZT. Introduction of 74V into RTs carrying TAMs partially
      counteracted the effect of TAMs on the rate of primer unblocking. The effect of
      74V was less marked than that of the 184V mutation in the 67N/70R/219Q and
      41L/210W/215Y RTs but similar in the RT carrying six TAMs. These results
      demonstrate that L74V enhances AZT susceptibility by reducing the extent of its
      removal by ATP-dependent phosphorolysis and provides further evidence for a
      common mechanism by which mutations conferring resistance to didanosine and
      lamivudine sensitize HIV-1 to AZT.

PMID- 15980333
TI  - Impaired rescue of chain-terminated DNA synthesis associated with the L74V
      mutation in human immunodeficiency virus type 1 reverse transcriptase.
AB  - The L74V and M184V mutations in the reverse transcriptase (RT) gene of human
      immunodeficiency virus type 1 (HIV-1) are frequently associated with resistance
      to the nucleoside reverse transcriptase inhibitors abacavir, didanosine, and
      lamivudine. Yet viruses containing any of these mutations often display
      hypersusceptibility to zidovudine (ZDV). Two distinct mechanisms have been
      described to explain HIV-1 drug resistance. One of these involves diminished
      rates of incorporation of the nucleotide analogue by mutated RT, while the other
      mechanism involves increased rates of phosphorolytic excision of the drug
      terminated primer. To understand the biochemical mechanisms responsible for the
      hypersensitization of L74V-containing viruses to ZDV, we studied the efficiency
      of excision of ZDV-monophosphate (ZDV-MP)-terminated primers by recombinant wild
      type and mutated HIV-1 RTs in cell-free assays. We observed that the L74V
      mutation in RT caused reductions in ATP-dependent removal of ZDV-MP from newly
      synthesized viral DNA. In addition, we determined that the L74V and M184V
      mutations did not affect the ratio between the populations of RT-DNA/DNA
      complexes found at pre- and posttranslocational stages; however, they might have
      affected proper alignment between incorporated chain terminator and pyrophosphate
      donor, substrate orientation, affinity for ATP, and/or primer-template substrate.
      Finally, we confirmed previous findings that L74V-containing viruses display
      diminished replication capacity and that this is associated with reduced levels
      of synthesis of early reverse-transcribed viral DNA molecules.

PMID- 15980334
TI  - Antimicrobial activity of novel dendrimeric peptides obtained by phage display
      selection and rational modification.
AB  - A large 10-mer phage peptide library was panned against whole Escherichia coli
      cells, and an antimicrobial peptide (QEKIRVRLSA) was selected. The peptide was
      synthesized in monomeric and dendrimeric tetrabranched form (multiple antigen
      peptide [MAP]), which generally allows a dramatic increase of peptide stability
      to peptidases and proteases. The antibacterial activity of the dendrimeric
      peptide against E. coli was much higher than that of the monomeric form.
      Modification of the original sequence, by residue substitution or sequence
      shortening, produced three different MAPs, M4 (QAKIRVRLSA), M5 (KIRVRLSA), and M6
      (QKKIRVRLSA) with enhanced stability to natural degradation and antimicrobial
      activity against a large panel of gram-negative bacteria. The MICs of the most
      potent peptide, M6, were as low as 4 to 8 microg/ml against recent clinical
      isolates of multidrug-resistant Pseudomonas aeruginosa and members of the
      Enterobacteriaceae. The same dendrimeric peptides showed high stability to blood
      proteases, low hemolytic activity, and low cytotoxic effects on eukaryotic cells,
      making them promising candidates for the development of new antibacterial drugs.

PMID- 15980335
TI  - Correlation between ratio of serum doxycycline concentration to MIC and rapid
      decline of antibody levels during treatment of Q fever endocarditis.
AB  - Endocarditis is the major clinical manifestation of chronic Q fever. Although
      doxycycline along with hydroxychloroquine remains the mainstay of medical therapy
      for Q fever endocarditis, there are wide variations in the rapidity of the
      patient's decline of antibody levels during such therapy. We undertook a
      retrospective examination of whether there was any correlation between the ratio
      of serum concentration to MIC of doxycycline and response to treatment in
      patients with Q fever endocarditis. Included herein are 16 patients from whom
      Coxiella burnetii was isolated from cardiac valve materials. Serology and
      measurement of doxycycline and hydroxychloroquine serum levels were performed and
      recorded after 1 year of treatment. The MIC of doxycycline for C. burnetii
      isolates was determined using the shell vial assay in a real-time quantitative
      PCR assay. At the completion of a year-long therapy with doxycycline
      hydroxychloroquine, all those that showed a low decline of antibody levels (n =
      6) (i.e., <2-fold decrease in antibody titer to phase I C. burnetii antigen) had
      a ratio of serum doxycycline concentration to MIC between 0.5 and 1. In contrast,
      those having a ratio of > or =1 showed a rapid decline of phase I antibody levels
      (n = 9; P < 0.05). The only patient who died had a serum doxycycline-to-MIC ratio
      of <0.5, and the isolate of C. burnetii cultured from this patient was resistant
      to doxycycline (MIC = 8 microg/ml). The ratio of serum doxycycline concentration
      to MIC should be monitored during the course of therapy in patients with Q fever
      endocarditis.

PMID- 15980336
TI  - Alteration of fatty acid and sterol metabolism in miltefosine-resistant
      Leishmania donovani promastigotes and consequences for drug-membrane
      interactions.
AB  - Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active drug
      approved for the treatment of visceral leishmaniasis. In order to investigate the
      biochemical modifications occurring in HePC-resistant (HePC-R) Leishmania
      donovani promastigotes, taking into account the lipid nature of HePC, we
      investigated their fatty acid and sterol metabolisms. We found that the content
      of unsaturated phospholipid alkyl chains was lower in HePC-R parasite plasma
      membranes than in those of the wild type, suggesting a lower fluidity of HePC-R
      parasite membranes. We also demonstrated that HePC insertion within an external
      monolayer was more difficult when the proportion of unsaturated phospholipids
      decreased, rendering the HePC interaction with the external monolayer of HePC-R
      parasites more difficult. Furthermore, HePC-R parasite membranes displayed a
      higher content of short alkyl chain fatty acids, suggesting a partial
      inactivation of the fatty acid elongation enzyme system in HePC-R parasites.
      Sterol biosynthesis was found to be modified in HePC-R parasites, since the 24
      alkylated sterol content was halved in HePC-R parasites; however, this
      modification was not related to HePC sensitivity. In conclusion, HePC resistance
      affects three lipid biochemical pathways: fatty acid elongation, the desaturase
      system responsible for fatty acid alkyl chain unsaturation, and the C-24
      alkylation of sterols.

PMID- 15980337
TI  - Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet
      microbicidal protein correlates with defective autolysis and loss of accessory
      gene regulator (agr) function.
AB  - Loss of agr function, vancomycin exposure, and abnormal autolysis have been
      linked with both development of the GISA phenotype and low-level resistance in
      vitro to thrombin-induced platelet microbicidal proteins (tPMPs). We examined the
      potential in vitro interrelationships among these parameters in well
      characterized, isogenic laboratory-derived and clinical Staphylococcus aureus
      isolates. The laboratory-derived S. aureus strains included RN6607 (agrII
      positive parent) and RN6607V (vancomycin-passaged variant; hetero-GISA), RN9120
      (RN6607 agr::tetM; agr II knockout parent), RN9120V (vancomycin-passaged
      variant), and RN9120-GISA (vancomycin passaged, GISA). Two serial isolates from a
      vancomycin-treated patient with recalcitrant, methicillin-resistant S. aureus
      (MRSA) endocarditis were also studied: A5937 (agrII-positive initial isolate) and
      A5940 (agrII-defective/hetero-GISA isolate obtained after prolonged vancomycin
      administration). In vitro tPMP susceptibility phenotypes were assessed after
      exposure of strains to either 1 or 2 mug/ml. Triton X-100- and vancomycin-induced
      lysis profiles were determined spectrophotometrically. For agrII-intact strain
      RN6607, vancomycin exposure in vitro was associated with modest increases in
      vancomycin MICs and reduced killing by tPMP, but no change in lysis profiles. In
      contrast, vancomycin exposure of agrII-negative RN9120 yielded a hetero-GISA
      phenotype and was associated with defects in lysis and reduced in vitro killing
      by tPMP. In the clinical isolates, loss of agrII function during prolonged
      vancomycin therapy was accompanied by emergence of the hetero-GISA phenotype and
      reduced tPMP killing, with no significant change in lysis profiles. An
      association was identified between loss of agrII function and the emergence of
      hetero-GISA phenotype during either in vitro or in vivo vancomycin exposure. In
      vitro, these events were associated with defective lysis and reduced
      susceptibility to tPMP. The precise mechanism(s) underlying these findings is the
      subject of current investigations.

PMID- 15980338
TI  - Population structure of Enterococcus faecium causing bacteremia in a Spanish
      university hospital: setting the scene for a future increase in vancomycin
      resistance?
AB  - Over an 8-year period (1995 to 2002), 86 Enterococcus faecium blood isolates from
      84 patients, of which 54 were ampicillin resistant (AREF) and 32 were ampicillin
      susceptible (ASEF), were studied in a university hospital (1,200 beds; serving a
      population of 600,000) in Spain, a country characterized by a near-absence of
      resistance to vancomycin and very high rates of ampicillin resistance among
      enterococci. Clonal relatedness by pulsed-field gel electrophoresis (PFGE),
      antibiotic susceptibility, presence of the virulence/epidemicity genes esp(Efm)
      and hyl(Efm), and identification of purK alleles were studied. A group of
      isolates was also analyzed by amplified fragment length polymorphism (AFLP) and
      multilocus sequence typing. Medical charts (30 variables collected) were reviewed
      for 60/84 patients. ASEF showed high clonal diversity (32 PFGE types, 11 purK
      alleles, 4 AFLP genogroups), did not harbor putative virulence genes, and had no
      specific association with hospital acquisition. AREF isolates belonged to a
      clonal complex (CC) of genetically related strains (purK-1, AFLP genogroup C),
      occasionally harboring putative virulence traits, and were from patients with
      particular risk factors. Within this CC, previously associated with vancomycin
      resistant E. faecium isolates causing outbreaks worldwide (W. L. Homan et al., J.
      Clin. Microbiol. 40:1963-1971, 2002), a great genetic diversity of antibiotic
      resistance and virulence/epidemicity profiles was found. Associations between esp
      and a >7-day hospital stay and between purK-1, hospital location, and nosocomial
      acquisition were noted (P < 0.001). These findings reflect the importance of
      local environmental differences in the evolution of this CC, suggesting that the
      emergence of vancomycin resistance among AREF strains in Spain may be a question
      of time.

PMID- 15980339
TI  - Differential gene expression in benznidazole-resistant Trypanosoma cruzi
      parasites.
AB  - We analyzed the differential gene expression among representative Trypanosoma
      cruzi stocks in relation to benznidazole exposures using a random differentially
      expressed sequences (RADES) technique. Studies were carried out with drug
      pressure both at the natural susceptibility level of the wild-type parasite (50%
      inhibitory concentration for the wild type) and at different resistance levels.
      The pattern of differential gene expression performed with resistant stocks was
      compared to the population structure of this parasite, established by random
      amplified polymorphic DNA analysis and multilocus enzyme electrophoresis. A RADES
      band polymorphism was observed, and over- or underexpression was linked to the
      resistance level of the stock. The analysis of RADES bands suggested that
      different products may be involved in benznidazole resistance mechanisms. No
      significant association was found between phylogenetic clustering and
      benznidazole susceptibility. Benznidazole resistance may involve several
      mechanisms, depending on the level of drug exposure.

PMID- 15980340
TI  - Phenotyping of cytomegalovirus drug resistance mutations by using recombinant
      viruses incorporating a reporter gene.
AB  - A new recombinant phenotyping method was developed for the analysis of drug
      resistance mutations in human cytomegalovirus (CMV). CMV strain T2211 was derived
      from strain AD169 by inserting unique restriction sites and a secreted alkaline
      phosphatase (SEAP) reporter gene for rapid viral quantitation. Specific viral
      UL97 and pol gene mutations were transferred by recombination into T2211, and
      their drug resistance phenotypes (for ganciclovir, foscarnet, or cidofovir) were
      determined by the drug concentrations required to reduce supernatant SEAP
      activity by 50% (IC50). Changes in the IC50 conferred by the mutations tested
      (UL97 M460V, C592G, A594V, and L595S and pol del981-2) were similar to those
      previously reported in marker transfer and conventional plaque reduction assays.
      The combination of UL97 C592G and pol del981-2 conferred much higher ganciclovir
      resistance than either mutation alone. The UL97 polymorphism D605E had no
      measurable effect on ganciclovir susceptibility, alone or in combination with
      common UL97 resistance mutations. Transfer into strain T2211 facilitates the
      phenotyping of newly observed mutations, combinations of mutations, and clinical
      CMV sequences without an accompanying viral isolate.

PMID- 15980341
TI  - New lnu(C) gene conferring resistance to lincomycin by nucleotidylation in
      Streptococcus agalactiae UCN36.
AB  - Streptococcus agalactiae UCN36 was resistant to lincomycin (MIC = 16 microg/ml)
      but susceptible to clindamycin (MIC = 0.12 microg/ml) and erythromycin (MIC =
      0.06 microg/ml). A 4-kb HindIII fragment was cloned from S. agalactiae UCN36
      total DNA on plasmid pUC18 and introduced into Escherichia coli AG100A, where it
      conferred resistance to lincomycin. The sequence analysis of the fragment showed
      the presence of a 1,724-bp element delineated by imperfect inverted repeats (22
      of 25 bp) and inserted in the operon for capsular synthesis of S. agalactiae
      UCN36. This element carried two open reading frames (ORF). The deduced amino acid
      sequence of the upstream ORF displayed similarity with transposases from
      anaerobes and IS1. The downstream ORF, lnu(C), encoded a 164-amino-acid protein
      with 26% to 27% identity with the LnuA(N2), LnuA, and LnuA' lincosamide
      nucleotidyltransferases reported for Bacteroides and Staphylococcus,
      respectively. Crude lysates of E. coli AG100A containing the cloned lnu(C) gene
      inactivated lincomycin and clindamycin in the presence of ATP and MgCl2. Mass
      spectrometry experiments demonstrated that the LnuC enzyme catalyzed
      adenylylation of lincomycin.

PMID- 15980343
TI  - Antibacterial properties of some cyclic organobismuth(III) compounds.
AB  - Bismuth compounds are known for their low levels of toxicity in mammals, and
      various types of bismuth salts have been used to treat medical disorders. As part
      of our program to probe this aspect of bismuth chemistry, cyclic organobismuth
      compounds 1 to 8 bearing a nitrogen or sulfur atom as an additional ring member
      have been synthesized, and their antimicrobial activities against five standard
      strains of gram-negative and gram-positive bacteria were assessed. The eight
      membered-ring compounds, compounds 1 to 3, exhibited MICs of less than 0.5
      microg/ml against Staphylococcus aureus and were more active than the six
      membered ones, compounds 5 to 8 (MICs, 4.0 to 16 microg/ml). The gram-positive
      bacteria (Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis)
      were more susceptible to both types of ring compounds than the gram-negative ones
      (Escherichia coli and Pseudomonas aeruginosa). Treatment with polymyxin B
      nonapeptide increased the susceptibility of E. coli to cyclic organobismuth
      compounds, indicating the low permeability of the outer membrane of gram-negative
      bacteria to the compounds. Compound 1 also had activity against methicillin
      resistant S. aureus, which had an MIC for 90% of the hospital stock strains of
      1.25 microg/ml. The killing curves for S. aureus treated with compound 1 or 3
      revealed a static effect at a low dose (2x the MIC). However, when S. aureus was
      treated with 10x the MIC of compound 1 or 3, there was an approximately 3-log
      reduction in the viable cell number after 48 h of treatment. Electron microscopic
      inspection demonstrated a considerable increase in the size of S. aureus and the
      proportion of cells undergoing cell division after treatment with compound 1 at
      0.5x the MIC.

PMID- 15980342
TI  - Antiviral effect of oral administration of tenofovir disoproxil fumarate in
      woodchucks with chronic woodchuck hepatitis virus infection.
AB  - Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue approved for
      treatment of human immunodeficiency virus (HIV) infection. TDF also has been
      shown in vitro to inhibit replication of wild-type hepatitis B virus (HBV) and
      lamivudine-resistant HBV mutants and to inhibit lamivudine-resistant HBV in
      patients and HBV in patients coinfected with the HIV. Data on the in vivo
      efficacy of TDF against wild-type virus in non-HIV-coinfected or lamivudine-naive
      chronic HBV-infected patients are lacking in the published literature. The
      antiviral effect of oral administration of TDF against chronic woodchuck
      hepatitis virus (WHV) infection, an established and predictive animal model for
      antiviral therapy, was evaluated in a placebo-controlled, dose-ranging study
      (doses, 0.5 to 15.0 mg/kg of body weight/day). Four weeks of once-daily treatment
      with TDF doses of 0.5, 1.5, or 5.0 mg/kg/day reduced serum WHV viremia
      significantly (0.2 to 1.5 log reduction from pretreatment level). No effects on
      the levels of anti-WHV core and anti-WHV surface antibodies in serum or on the
      concentrations of WHV RNA or WHV antigens in the liver of treated woodchucks were
      observed. Individual TDF-treated woodchucks demonstrated transient declines in
      WHV surface antigen serum antigenemia and, characteristically, these woodchucks
      also had transient declines in serum WHV viremia, intrahepatic WHV replication,
      and hepatic expression of WHV antigens. No evidence of toxicity was observed in
      any of the TDF-treated woodchucks. Following drug withdrawal there was prompt
      recrudescence of WHV viremia to pretreatment levels. It was concluded that oral
      administration of TDF for 4 weeks was safe and effective in the woodchuck model
      of chronic HBV infection.

PMID- 15980344
TI  - Short-course gentamicin in combination with daptomycin or vancomycin against
      Staphylococcus aureus in an in vitro pharmacodynamic model with simulated
      endocardial vegetations.
AB  - The ability to maximize bactericidal activity while minimizing toxicity is a
      therapeutic goal in the treatment of infective endocarditis. We evaluated the
      impact of administering short-course regimens of gentamicin in combination with
      daptomycin or vancomycin against one methicillin-susceptible (MSSA 1199) and one
      methicillin-resistant (MRSA 494) Staphylococcus aureus isolate using an in vitro
      pharmacodynamic model with simulated endocardial vegetations over 96 h. Human
      therapeutic dosing regimens for daptomycin (6 and 8 mg/kg of body weight),
      vancomycin, and gentamicin were simulated. Short-course combination regimens
      involving gentamicin were administered either as a single 5-mg/kg dose or three 1
      mg/kg doses for only the first 24 h and compared to the regimens administered for
      the full 96-h duration. For all experiments, physiologic conditions of albumin,
      calcium, and pH were simulated. Both regimens of daptomycin achieved 99.9% kill
      by 32 h and maintained bactericidal activity against both isolates, which was
      significantly different from vancomycin, which displayed bacteriostatic activity
      (P < 0.05). The effects of all short-course regimens of gentamicin were equal to
      those of the full-duration regimens in combination with daptomycin. Adding three
      doses of gentamicin (1 mg/kg) to daptomycin resulted in enhancement and
      bactericidal activity at 24 h against both MRSA and MSSA. The addition of a
      single dose of gentamicin (5 mg/kg) enhanced or improved the activity of
      daptomycin and resulted in early bactericidal activity at 4 h against both
      isolates. The addition of three doses of gentamicin (1 mg/kg) did not improve the
      activity of vancomycin. However, the addition of a single 5-mg/kg dose of
      gentamicin to vancomycin resulted in early enhancement at 4 h and 99.9% kill at
      32 h for MRSA. These results suggest that a single high dose of gentamicin in
      combination with daptomycin or vancomycin may be of utility to maximize
      synergistic and bactericidal activity and minimize toxicity. Further
      investigation is warranted.

PMID- 15980345
TI  - Constitutive soxR mutations contribute to multiple-antibiotic resistance in
      clinical Escherichia coli isolates.
AB  - The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox
      cycling compounds or nitric oxide and provides resistance to superoxide
      generating agents, macrophage-generated nitric oxide, antibiotics, and organic
      solvents. We have previously shown that constitutive expression of soxRS can
      contribute to quinolone resistance in clinically relevant S. enterica. In this
      work, we have carried out an analysis of the mechanism of constitutive soxS
      expression and its role in antibiotic resistance in E. coli clinical isolates. We
      show that constitutive soxS expression in three out of six strains was caused by
      single point mutations in the soxR gene. The mutant SoxR proteins contributed to
      the multiple-antibiotic resistance phenotypes of the clinical strains and were
      sufficient to confer multiple-antibiotic resistance in a fresh genetic
      background. In the other three clinical isolates, we observed, for the first
      time, that elevated soxS expression was not due to mutations in soxR. The
      mechanism of such increased soxS expression remains unclear. The same E. coli
      clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for
      the first time.

PMID- 15980346
TI  - Macrolide resistance in Campylobacter jejuni and Campylobacter coli: molecular
      mechanism and stability of the resistance phenotype.
AB  - A collection of 23 macrolide-resistant Campylobacter isolates from different
      geographic areas was investigated to determine the mechanism and stability of
      macrolide resistance. The isolates were identified as Campylobacter jejuni or
      Campylobacter coli based on the results of the hippurate biochemical test in
      addition to five PCR-based genotypic methods. Three point mutations at two
      positions within the peptidyl transferase region in domain V of the 23S rRNA gene
      were identified. About 78% of the resistant isolates exhibited an A-->G
      transition at Escherichia coli equivalent base 2059 of the 23S rRNA gene. The
      isolates possessing this mutation showed a wide range of erythromycin and
      clarithromycin MICs. Thus, this mutation may incur a greater probability of
      treatment failure in populations infected by resistant Campylobacter isolates.
      Another macrolide-associated mutation (A-->C transversion), at E. coli equivalent
      base 2058, was detected in about 13% of the isolates. An A-->G transition at a
      position cognate with E. coli 23S rRNA base 2058, which is homologous to the
      A2142G mutation commonly described in Helicobacter pylori, was also identified in
      one of the C. jejuni isolates examined. In the majority of C. jejuni isolates,
      the mutations in the 23S rRNA gene were homozygous except in two cases where the
      mutation was found in two of the three copies of the target gene. Natural
      transformation demonstrated the transfer of the macrolide resistance phenotype
      from a resistant Campylobacter isolate to a susceptible Campylobacter isolate.
      Growth rates of the resulting transformants containing A-2058-->C or A-2059-->G
      mutations were similar to that of the parental isolate. The erythromycin
      resistance of six of seven representative isolates was found to be stable after
      successive subculturing in the absence of erythromycin selection pressure
      regardless of the resistance level, the position of the mutation, or the number
      of the mutated copies of the target gene. One C. jejuni isolate showing an A-2058
      ->G mutation, however, reverted to erythromycin and clarithromycin susceptibility
      after 55 subcultures on erythromycin-free medium. Investigation of ribosomal
      proteins L4 and L22 by sequence analysis in five representative isolates of C.
      jejuni and C. coli demonstrated no significant macrolide resistance-associated
      alterations in either the L4 or the L22 protein that might explain either
      macrolide resistance or enhancement of the resistance level.

PMID- 15980347
TI  - Population pharmacokinetics of cefepime in the neonate.
AB  - Newborn infants cared for in neonatal intensive care units may develop nosocomial
      infections. Cefepime, a "fourth-generation" cephalosporin (i.e., with activity
      against virtually all of the chromosomal-beta-lactamase-producing and many
      extended-spectrum-beta-lactamase-producing organisms), provides excellent
      activity against many gram-negative pathogens resistant to expanded-spectrum
      cephalosporins currently used to treat neonatal infections. The purpose of this
      study was to determine the pharmacokinetics of cefepime in this population to
      optimize dosing and minimize potential adverse events. Premature and term infants
      <4 months of age hospitalized in two neonatal intensive care units were studied.
      Limited pharmacokinetic (PK) sampling occurred following a dose of cefepime at 50
      mg/kg of body weight infused over 30 min. Population pharmacokinetic parameters
      were determined using the program NONMEM. Fifty-five infants were enrolled. Their
      average (+/- standard deviation) gestational age at birth was 30.5 +/- 5.3 weeks,
      and their average postnatal age at PK evaluation was 14.5 +/- 14.7 days. In the
      final PK model, cefepime clearance (CL) was strongly associated with serum
      creatinine (SCr) (CL [ml/min/kg] = 0.26 + 0.59/SCr). The volume of distribution
      for infants with a postconceptional age of <30 weeks was larger than that for
      infants with a postconceptional age of >30 weeks (0.51 versus 0.39 liter/kg,
      respectively). The Bayesian analysis-predicted cefepime trough concentration at a
      dose of 50 mg/kg every 12 h for infants < or = 14 days of age was 29.9 +/- 16.6
      microg/ml. Cefepime, dosed at 30 mg/kg/dose every 12 h for infants less than 14
      days of age, regardless of gestational age, should provide antibiotic exposure
      equivalent to or greater than 50 mg/kg every 8 h in older infants and children.

PMID- 15980348
TI  - Novel approach to mapping of resistance mutations in whole genomes by using
      restriction enzyme modulation of transformation efficiency.
AB  - Restriction enzyme modulation of transformation efficiencies (REMOTE) is a method
      that makes use of genome restriction maps and experimentally observed differences
      in transformation efficiencies of genomic DNA restriction digests to discover the
      location of mutations in genomes. The frequency with which digested genomic DNA
      from a resistant strain transforms a susceptible strain to resistance is
      primarily determined by the size of the fragment containing the resistance
      mutation and the distance of the mutation to the end of the fragment. The
      positions of restriction enzyme cleavage sites immediately flanking the
      resistance mutation define these parameters. The mapping procedure involves a
      process of elimination in which digests that transform with high frequency
      indicate that the restriction enzyme cleavage sites are relatively far away from
      the mutation, while digests that transform with low frequency indicate that the
      sites are close to the mutation. The transformation data are compared
      computationally to the genome restriction map to identify the regions that best
      fit the data. Transformations with PCR amplicons encompassing candidate regions
      identify the resistance locus and enable identification of the mutation. REMOTE
      was developed using Haemophilus influenzae strains with mutations in gyrA, gyrB,
      and rpsE that confer resistance to ciprofloxacin, novobiocin, and spectinomycin,
      respectively. We applied REMOTE to identify mutations that confer resistance to
      two novel antibacterial compounds. The resistance mutations were found in genes
      that can decrease the intracellular concentration of compounds: acrB, which
      encodes a subunit of the AcrAB-TolC efflux pump; and fadL, which encodes a long
      chain fatty acid transporter.

PMID- 15980349
TI  - Structure-based phylogeny of the metallo-beta-lactamases.
AB  - The metallo-beta-lactamases fall into two groups: Ambler class B subgroups B1 and
      B2 and Ambler class B subgroup B3. The two groups are so distantly related that
      there is no detectable sequence homology between members of the two different
      groups, but homology is clearly detectable at the protein structure level. The
      multiple structure alignment program MAPS has been used to align the structures
      of eight metallo-beta-lactamases and five structurally homologous proteins from
      the metallo-beta-lactamase superfamily, and that alignment has been used to
      construct a phylogenetic tree of the metallo-beta-lactamases. The presence of
      genes from Eubacteria, Archaebacteria, and Eukaryota on that tree is consistent
      with a very ancient origin of the metallo-beta-lactamase family.

PMID- 15980350
TI  - Drug-induced regulation of the MDR1 promoter in Candida albicans.
AB  - Resistance of Candida albicans to azole antifungal drugs is mediated by two types
      of efflux pumps, encoded by the MDR1 gene and the CDR gene family. MDR1 mRNA
      levels in a susceptible clinical isolate are induced by benomyl (BEN) but not by
      other drugs previously shown to induce MDR1. To monitor MDR1 expression under
      several conditions, the MDR1 promoter was fused to the Renilla reniformis
      luciferase reporter gene (RLUC). The promoter was monitored for its responses to
      four oxidizing agents, five toxic hydrophobic compounds, and an alkylating agent,
      all shown to induce major facilitator pumps in other organisms. Deletion
      constructs of the MDR1 promoter were used to analyze the basal transcription of
      the promoter and its responses to the toxic compound BEN and the oxidizing agent
      tert-butyl hydrogen peroxide (T-BHP). The cis-acting elements in the MDR1
      promoter responsible for induction by BEN were localized between -399 and -299
      upstream of the start codon. The cis-acting elements responsible for MDR1
      induction by T-BHP were localized between -601 and -500 upstream of the start
      codon. The T-BHP induction region contains a sequence that resembles the YAP1
      responsive element (YRE) in Saccharomyces cerevisiae. This Candida YRE was placed
      upstream of a noninducible promoter in the luciferase construct, resulting in an
      inducible promoter. Inversion or mutation of the 7-bp YRE eliminated induction.
      Many of the drugs used in this analysis induce the MDR1 promoter at
      concentrations that inhibit cell growth. These analyses define cis-acting
      elements responsible for drug induction of the MDR1 promoter.

PMID- 15980351
TI  - Multiple-antibiotic resistance in Salmonella enterica serotype Paratyphi B
      isolates collected in France between 2000 and 2003 is due mainly to strains
      harboring Salmonella genomic islands 1, 1-B, and 1-C.
AB  - This study was conducted to investigate the occurrence of multiple-antibiotic
      resistance among 261 clinical isolates of Salmonella enterica serotype Paratyphi
      B strains collected between 2000 and 2003 through the network of the French
      National Reference Center for Salmonella. The 47 multidrug-resistant (MDR)
      isolates identified (18%), were characterized on the basis of the presence of
      several resistance genes (bla(TEM), bla(PSE-1), bla(CTX-M), floR, aadA2,
      qacEdelta1, and sul1), the presence of Salmonella genomic island 1 (SGI1) by PCR
      mapping and hybridization, and the clonality of these isolates by several
      molecular (ribotyping, IS200 profiling, and pulsed-field gel electrophoresis
      [PFGE]) and phage typing methods. The results of PCR and Southern blot
      experiments indicated that 39 (83%) of the 47 S. enterica serotype Paratyphi B
      biotype Java MDR isolates possessed the SGI1 cluster (MDR/SGI1). Among these 39
      MDR/SGI1 isolates, only 3 contained variations in SGI1, SGI1-B (n = 1) and SGI1-C
      (n = 2). The 39 MDR/SGI1 isolates showed the same specific PstI-IS200 profile 1,
      which contained seven copies from 2.6 to 18 kb. Two PstI ribotypes were found in
      MDR/SGI1 isolates, RP1 (n = 38) and RP6 (n = 1). Ribotype RP1 was also found in
      two susceptible strains. Analysis by PFGE using XbaI revealed that all the
      MDR/SGI1 isolates were grouped in two related clusters, with a similarity
      percentage of 82%. Isolation of MDR/SGI1 isolates in France was observed mainly
      between the second quarter of 2001 and the end of 2002. The source of the
      contamination has not been identified to date. A single isolate possessing the
      extended-spectrum beta-lactamase bla(CTX-M-15) gene was also identified during
      the study.

PMID- 15980352
TI  - Pharmacokinetics and short-term safety of 873140, a novel CCR5 antagonist, in
      healthy adult subjects.
AB  - 873140 is a novel CCR5 antagonist with potent in vitro anti-human
      immunodeficiency virus (HIV) activity. This study was a double-blind, randomized,
      placebo-controlled, single- and repeat-dose escalation investigation of the
      safety, pharmacokinetics, and food effect of 873140 in 70 adult subjects. During
      single-dose escalation, three cohorts (each composed of 10 subjects, with 8
      subjects receiving the active drug and 2 subjects receiving the placebo [8 active
      and 2 placebo]) received doses of 50, 200, 400, 800, and 1,200 mg after an
      overnight fast, or 400 mg plus a standard high-fat breakfast in an alternating
      panel design. During repeat-dose escalation, four cohorts (each with 8 active and
      2 placebo) received doses of 200, 400, 600, or 800 mg every 12 h (BID) for 8
      days. Laboratory safety tests, vital signs, and electrocardiograms (ECGs) were
      performed at regular intervals, and blood samples were obtained for
      pharmacokinetics. Single and repeat doses of 50 mg to 800 mg were well tolerated,
      with no serious adverse events and no grade 3 or 4 adverse events. The mild-to
      moderate side effects were primarily gastrointestinal and included abdominal
      cramping, nausea, and diarrhea. No specific trends in laboratory parameters or
      clinically significant ECG changes were noted. Plasma 873140 concentrations
      increased rapidly; the median time to maximum concentration of drug in serum was
      1.75 to 5 h. The median area under the plasma concentration-time profile (AUC)
      and the maximum concentration of drug in serum (C(max)) ranged from 127 ng.h/ml
      and 24 ng/ml at 200 mg BID to 329 ng.h/ml and 100 ng/ml at 800 mg BID,
      respectively. Food consumption increased the AUC and C(max) by a mean of 1.7- and
      2.2-fold, respectively. The pharmacokinetic and safety profile supports the
      continued investigation of 873140 with HIV-infected subjects.

PMID- 15980353
TI  - Sixteen homologs of the mex-type multidrug resistance efflux pump in Bacteroides
      fragilis.
AB  - Sixteen homologs of multidrug resistance efflux pump operons of the resistance
      nodulation-cell division (RND) family were found in the Bacteroides fragilis
      genome sequence by homology searches. Disruption mutants were made to the mexB
      homologs of the four genes most similar to Pseudomonas aeruginosa mexB. Reverse
      transcription-PCR was conducted and indicated that the genes were transcribed in
      a polycistronic fashion and that the promoter was upstream of bmeA (the mexA
      homolog). One of these disruption mutants (in bmeB, the mexB homolog) was more
      susceptible than the parental strain to certain cephems, polypeptide antibiotics,
      fusidic acid, novobiocin, and puromycin. The gene for this homolog and the
      adjacent upstream gene, bmeA, were cloned in a hypersensitive Escherichia coli
      host. The resultant transformants carrying B. fragilis bmeAB were more resistant
      to certain agents; these agents also had lower MICs for the B. fragilis bmeB
      disruption mutants than for the parental strain. The putative efflux pump operon
      is composed of bmeA, bmeB, and bmeC (a putative outer membrane channel protein
      homologous with OprM). Addition of the efflux pump inhibitors, carbonyl cyanide m
      chlorophenylhydrazone (a proton conductor that eliminates the energy source) and
      Phe-Arg beta-naphthylamide (MC-207,110) (the first specific inhibitor described
      for RND pumps in P. aeruginosa), resulted in lowered MICs in the parental strain
      but not in the bmeB disruption mutant, indicating that the bmeB pump is affected
      by these inhibitors. This is the first description of RND type pumps in the genus
      Bacteroides.

PMID- 15980354
TI  - Imipenem for treatment of tuberculosis in mice and humans.
AB  - Chemotherapy of tuberculosis caused by multiple-drug-resistant (MDR) strains is
      problematic because of choices limited to relatively inefficacious and toxic
      drugs. Some beta-lactam antibiotics are active against Mycobacterium tuberculosis
      in vitro. We investigated the efficacy of imipenem in a mouse model of
      tuberculosis and in humans with MDR tuberculosis. Mice infected with M.
      tuberculosis strain H37Rv were treated with isoniazid or imipenem. Residual
      organisms in lung and spleen and survival of imipenem-treated mice were compared
      to those of untreated or isoniazid-treated mice. Ten patients with MDR
      tuberculosis also were treated with imipenem in combination with other first- or
      second-line agents; elimination of M. tuberculosis from sputum samples was
      measured by quantitative culture. Although it was less effective than isoniazid,
      imipenem significantly reduced the numbers of M. tuberculosis organisms in lungs
      and spleens and improved survival of mice. Eight of 10 patients with numerous
      risk factors for poor outcomes responded to imipenem combination therapy with
      conversion of cultures to negative. Seven remained culture-negative off of
      therapy. There were two deaths, one of which was due to active tuberculosis.
      Organisms were eliminated from the sputa of responders at a rate of 0.35 log10
      CFU/ml/week. Relapse upon withdrawal of imipenem and development of resistance to
      imipenem in a nonresponder suggest that imipenem exerts antimycobacterial
      activity in humans infected with M. tuberculosis. Imipenem had antimycobacterial
      activity both in a mouse model and in humans at high risk for failure of
      treatment for MDR tuberculosis.

PMID- 15980355
TI  - Helicobacter pylori accumulates photoactive porphyrins and is killed by visible
      light.
AB  - Helicobacter pylori colonizes the mucus layer of the human stomach and duodenum,
      causes chronic gastritis, gastric ulcer, and is a risk factor for gastric
      adenocarcinoma. There is a 20% failure rate in antibiotic therapy, which is
      increasingly due to antibiotic resistance and necessitates the search for
      alternative antimicrobial methods. We have discovered that H. pylori when
      cultured in liquid medium, accumulates significant quantities of coproporphyrin
      and protoporphyrin IX, both in the cells and secreted into the medium. These
      photoactive porphyrins lead to cell death (up to 5 logs) by photodynamic action
      upon illumination with low doses of visible light, with blue/violet light being
      most efficient. The degree of killing increases with the age of the culture and
      is greater than that found with Propionibacterium acnes (another bacterium known
      to be photosensitive due to porphyrin accumulation). Both virulent and drug
      resistant strains are killed. The data suggest that phototherapy might be used to
      treat H. pylori infection in the human stomach.

PMID- 15980356
TI  - Safety, pharmacokinetics, and efficacy of (+/-)-beta-2',3'-dideoxy-5-fluoro-3'
      thiacytidine with efavirenz and stavudine in antiretroviral-naive human
      immunodeficiency virus-infected patients.
AB  - Racivir [RCV; (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine], a 50:50 racemic
      mixture of the two beta nucleoside enantiomers, is currently in development for
      the treatment of human immunodeficiency virus type 1 (HIV-1) infections. RCV was
      administered once a day orally for 14 days at doses of 200, 400, or 600 mg in
      combination with stavudine and efavirenz to HIV-1-infected treatment-naive male
      volunteers in a phase Ib/IIa study. Six volunteers at each dose were monitored
      for a total of 35 days for tolerance, pharmacokinetics, and plasma HIV RNA
      levels. RCV in combination with stavudine and efavirenz was well tolerated at all
      doses tested. Pharmacokinetic parameters were dose proportional, and the maximum
      concentration of drug in serum at all doses exceeded the 90% effective
      concentration for wild-type HIV-1. Viral loads dropped as expected in all dosage
      groups, with mean reductions from 1.13 to 1.42 log10 by day 4 and 2.02 to 2.43
      log10 by day 14. HIV RNA levels remained suppressed for more than 2 weeks in the
      absence of any additional therapy, with mean viral loads ranging from 2.1 to 2.6
      log10 below baseline through day 28. By day 35, HIV RNA levels began to increase
      but still remained >1 log10 below baseline levels.

PMID- 15980357
TI  - Genetic approach to study the relationship between penicillin-binding protein 3
      mutations and Haemophilus influenzae beta-lactam resistance by using site
      directed mutagenesis and gene recombinants.
AB  - To clarify the relationship between mutations commonly found for penicillin
      binding protein 3 (PBP 3) of beta-lactamase-nonproducing ampicillin-resistant
      (BLNAR) Haemophilus influenzae isolates and beta-lactam resistance, single and
      multiple amino acid mutations at positions 377, 385, 389, 517, and 526 were
      introduced into PBP 3 of a beta-lactam-susceptible Rd strain by site-directed
      mutagenesis. Twelve isogenic recombinant strains were challenged with nine beta
      lactam antibiotics. Replacement of the asparagine at position 526 with lysine
      (N526K) increased the resistance to imipenem eightfold and increased the
      resistance to various cephalosporins two- to eightfold. Substitution of threonine
      for serine at position 385 (S385T) and/or substitution of phenylalanine for
      leucine at position 389 (L389F), in addition to the N526K mutation, led to two-
      to fourfold additional increases in cephalosporin resistance. An isoleucine-to
      methionine substitution at position 377 did not change the antibiotic sensitivity
      of any of the recombinant strains also carrying other PBP 3 mutations tested.
      Thirty-six clinical isolates carrying a PBP 3 gene (ftsI) with the S385T, L389F,
      R517H, and/or N526K mutation were chosen from among 279 clinical isolates
      collected in Japan, and the isolates were grouped into six classes on the basis
      of the patterns of the four mutations in PBP 3. Rd recombinants were made with
      each of the ftsI genes. The levels of resistance to beta-lactams varied between
      recombinants of different classes but were comparable for those of the same
      class. The levels of resistance to cephalosporins of these recombinants were
      similar to those of the parent clinical isolates, while those to ampicillin and
      carbapenems were lower. These results indicate that resistance to beta-lactams,
      at least to cephalosporins, depends in large part on the PBP 3 mutations R517H,
      N526K, S385T, and L389F.

PMID- 15980358
TI  - Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with
      resistance to terbinafine.
AB  - There has only been one clinically confirmed case of terbinafine resistance in
      dermatophytes, where six sequential Trichophyton rubrum isolates from the same
      patient were found to be resistant to terbinafine and cross-resistant to other
      squalene epoxidase (SE) inhibitors. Microsomal SE activity from these resistant
      isolates was insensitive to terbinafine, suggesting a target-based mechanism of
      resistance (B. Favre, M. Ghannoum, and N. S. Ryder, Med. Mycol. 42:525-529,
      2004). In this study, we have characterized at the molecular level the cause of
      the resistant phenotype of these clinical isolates. Cloning and sequencing of the
      SE gene and cDNA from T. rubrum revealed the presence of an intron in the gene
      and an open reading frame encoding a protein of 489 residues, with an equivalent
      similarity (57%) to both yeast and mammalian SEs. The nucleotide sequences of SE
      from two terbinafine-susceptible strains were identical whereas those of
      terbinafine-resistant strains, serially isolated from the same patient, each
      contained the same single missense introducing the amino acid substitution L393F.
      Introduction of the corresponding substitution in the Candida albicans SE gene
      (L398F) and expression of this gene in Saccharomyces cerevisiae conferred a
      resistant phenotype to the transformants when compared to those expressing the
      wild-type sequence. Terbinafine resistance in these T. rubrum clinical isolates
      appears to be due to a single amino acid substitution in SE.

PMID- 15980359
TI  - Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization,
      cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37.
AB  - Antimicrobial peptides have been evaluated in vitro and in vivo as alternatives
      to conventional antibiotics. Apart from being antimicrobial, the native human
      cathelicidin-derived peptide LL-37 (amino acids [aa] 104 to 140 of the human
      cathelicidin antimicrobial peptide) also binds and neutralizes bacterial
      lipopolysaccharide (LPS) and might therefore have beneficial effects in the
      treatment of septic shock. However, clinical trials have been hampered by
      indications of toxic effects of LL-37 on mammalian cells and evidence that its
      antimicrobial effects are inhibited by serum. For the present study, LL-37 was
      compared to two less hydrophobic fragments obtained by N-terminal truncation,
      named 106 (aa 106 to 140) and 110 (aa 110 to 140), and to a previously described
      more hydrophobic variant, the 18-mer LLKKK, concerning antimicrobial properties,
      lipopolysaccharide neutralization, toxicity against human erythrocytes and
      cultured vascular smooth muscle cells, chemotactic activity, and inhibition by
      serum. LL-37, fragments 106 and 110, and the 18-mer LLKKK inhibited the growth of
      Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida
      albicans in a radial diffusion assay, inhibited lipopolysaccharide-induced
      vascular nitric oxide production, and attracted neutrophil granulocytes
      similarly. While fragments 106 and 110 caused less hemolysis and DNA
      fragmentation in cultured cells than did LL-37, the 18-mer LLKKK induced severe
      hemolysis. The antibacterial effect of fragments 106 and 110 was not affected by
      serum, while the effect of LL-37 was reduced. We concluded that the removal of N
      terminal hydrophobic amino acids from LL-37 decreases its cytotoxicity as well as
      its inhibition by serum without negatively affecting its antimicrobial or LPS
      neutralizing action. Such LL-37-derived peptides may thus be beneficial for the
      treatment of patients with sepsis.

PMID- 15980360
TI  - Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase
      activity is sensitive to echinocandins.
AB  - (1,3)Beta-D-glucan synthase (EC 2.4.1.34. UDP-glucose: 1,3-beta-D-glucan 3-beta
      glucosyltransferase) uses UDP-glucose as substrate and catalyzes the
      polymerization of glucose ([1,3]-beta-linkages) to form the major carbohydrate
      component of the fungal cell wall. We have optimized in vitro assay conditions
      for (1,3)beta-glucan synthase activity from Cryptococcus neoformans. Cells lysed
      in 50 mM Tris, pH 7.75, containing 20% glycerol, 2 mM NaF, 1 mM dithiothreitol,
      0.1 mM phenylmethylsulfonyl fluoride, 5 mM MgCl(2), 0.1% protease and phosphatase
      inhibitor cocktails, and 60 microM GTPgammaS produced maximum specific activity
      in vitro. We tested in vitro C. neoformans (1,3)beta-glucan synthase activity
      against the (1,3)beta-glucan synthase inhibitors, caspofungin and cilofungin, and
      have determined that (1,3)beta-glucan synthase activity is very sensitive
      (apparent K(i) of 0.17 +/- 0.02 microM and 22 +/- 5.7 microM, respectively) to
      these echinocandins. Taken together with high MICs for C. neoformans (caspofungin
      MIC, 16 microg/ml; cilofungin MIC, 64 microg/ml), our results indicate that C.
      neoformans is resistant to caspofungin and cilofungin by a mechanism(s) unrelated
      to (1,3)beta-glucan synthase resistance.

PMID- 15980361
TI  - 3-Aminooxy-1-aminopropane and derivatives have an antiproliferative effect on
      cultured Plasmodium falciparum by decreasing intracellular polyamine
      concentrations.
AB  - The intraerythrocytic development of Plasmodium falciparum correlates with
      increasing levels of the polyamines putrescine, spermidine, and spermine in the
      infected red blood cells; and compartmental analyses revealed that the majority
      is associated with the parasite. Since depletion of cellular polyamines is a
      promising strategy for inhibition of parasite proliferation, new inhibitors of
      polyamine biosynthesis were tested for their antimalarial activities. The
      ornithine decarboxylase (ODC) inhibitor 3-aminooxy-1-aminopropane (APA) and its
      derivatives CGP 52622A and CGP 54169A as well as the S-adenosylmethionine
      decarboxlyase (AdoMetDC) inhibitors CGP 40215A and CGP 48664A potently affected
      the bifunctional P. falciparum ODC-AdoMetDC, with K(i) values in the low
      nanomolar and low micromolar ranges, respectively. Furthermore, the agents were
      examined for their in vitro plasmodicidal activities in 48-h incubation assays.
      APA, CGP 52622A, CGP 54169A, and CGP 40215A were the most effective, with 50%
      inhibitory concentrations below 3 microM. While the effects of the ODC inhibitors
      were completely abolished by the addition of putrescine, growth inhibition by the
      AdoMetDC inhibitor CGP 40215A could not be antagonized by putrescine or
      spermidine. Moreover, CGP 40215A did not affect the cellular polyamine levels,
      indicating a mechanism of action against P. falciparum independent of polyamine
      synthesis. In contrast, the ODC inhibitors led to decreased cellular putrescine
      and spermidine levels in P. falciparum, supporting the fact that they exert their
      antimalarial activities by inhibition of the bifunctional ODC-AdoMetDC.

PMID- 15980363
TI  - Human volunteers receiving Escherichia coli phage T4 orally: a safety test of
      phage therapy.
AB  - Fifteen healthy adult volunteers received in their drinking water a lower
      Escherichia coli phage T4 dose (10(3) PFU/ml), a higher phage dose (10(5)
      PFU/ml), and placebo. Fecal coliphage was detected in a dose-dependent way in
      volunteers orally exposed to phage. All volunteers receiving the higher phage
      dose showed fecal phage 1 day after exposure; this prevalence was only 50% in
      subjects receiving the lower phage dose. No fecal phage was detectable a week
      after a 2-day course of oral phage application. Oral phage application did not
      cause a decrease in total fecal E. coli counts. In addition, no substantial phage
      T4 replication on the commensal E. coli population was observed. No adverse
      events related to phage application were reported. Serum transaminase levels
      remained in the normal range, and neither T4 phage nor T4-specific antibodies
      were observed in the serum of the subjects at the end of the study. This is, to
      our knowledge, the first safety test in the recent English literature which has
      measured the bioavailability of oral phage in humans and is thus a first step to
      the rational evaluation of phage therapy for diarrheal diseases.

PMID- 15980362
TI  - Frequency of spontaneous mutations that confer antibiotic resistance in Chlamydia
      spp.
AB  - Mutations in rRNA genes (rrn) that confer resistance to ribosomal inhibitors are
      typically recessive or weakly codominant and have been mostly reported for
      clinical strains of pathogens possessing only one or two rrn operons, such as
      Helicobacter pylori and Mycobacterium spp. An analysis of the genome sequences of
      several members of the Chlamydiaceae revealed that these obligate intracellular
      bacteria harbor only one or two sets of rRNA genes. To study the contribution of
      rRNA mutations to the emergence of drug resistance in the Chlamydiaceae, we used
      the sensitivities of Chlamydia trachomatis L2 (two rrn operons) and Chlamydophila
      psittaci 6BC (one rrn operon) to the aminoglycoside spectinomycin as a model.
      Confluent cell monolayers were infected in a plaque assay with about 10(8) wild
      type infectious particles and then treated with the antibiotic. After a 2-week
      incubation time, plaques formed by spontaneous spectinomycin-resistant (Spc(r))
      mutants appeared with a frequency of 5 x 10(-5) for C. psittaci 6BC. No Spc(r)
      mutants were isolated for C. trachomatis L2, although the frequencies of rifampin
      resistance were in the same range for both strains (i.e., 10(-7)). The risk of
      emergence of Chlamydia strains resistant to tetracyclines and macrolides, the
      ribosomal drugs currently used to treat chlamydial infections, is discussed.

PMID- 15980364
TI  - Colonization and resistance dynamics of gram-negative bacteria in patients during
      and after hospitalization.
AB  - The colonization and resistance dynamics of aerobic gram-negative bacteria in the
      intestinal and oropharyngeal microfloras of patients admitted to intensive care
      units (ICU) and general wards were investigated during and after hospitalization.
      A total of 3,316 specimens were obtained from patients upon admission, once
      weekly during hospitalization, at discharge from the ICU, at discharge from the
      hospital, and 1 and 3 months after discharge from the hospital. Five colonies per
      specimen were selected for identification and susceptibility testing. In both
      patient populations, the gram-negative colonization rates in oropharyngeal
      specimens increased during hospitalization and did not decrease in the 3 months
      after discharge. In rectal specimens, colonization rates decreased during
      hospitalization and increased after discharge. There was a change in species
      distribution among the dominant microfloras during hospitalization. Klebsiella
      spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa were
      isolated more often, whereas the frequency of Escherichia coli declined. The
      percentage of ICU patients colonized with ampicillin- and/or cephalothin
      resistant fecal E. coli was significantly increased at discharge from the
      hospital and did not change in the 3 months after discharge. The emergence of
      multidrug resistance was observed for E. coli during patient stays in the ICU.
      Resistance frequencies in E. coli significantly increased with the length of stay
      in the ICU. For the general ward population, no significant changes in resistance
      frequencies were found during hospitalization. From a population perspective, the
      risk of dissemination of resistant gram-negative bacteria into the community
      through hospitalized patients appears to be low for general ward patients but is
      noticeably higher among ICU patients.

PMID- 15980365
TI  - Efficacy of the antiadhesin octyl O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl)
      (1-4)-2-O-propyl-beta-D-galactopyranoside (Fimbrigal-P) in a rat oral candidiasis
      model.
AB  - Adherence of Candida albicans to buccal epithelial cells via its fimbrial subunit
      requires the minimal disaccharide sequence beta-GalNAc(1-4)-beta-galactosidase in
      host cell receptors asialo-GM1 or asialo-GM2. This and other disaccharides and
      some of its synthetic derivatives have been shown to inhibit purified fimbrial or
      pathogen binding in vitro. This study evaluates the in vivo efficacy of the
      propyl derivative of this disaccharide, octyl O-(2-acetamido-2-deoxy-beta-D
      galactopyranosyl)-(1-4)-2-O-propyl-beta-D-galactopyranoside, or Fimbrigal-P,
      incorporated into a mucoadhesive polymer formulation in a rat oral candidiasis
      model. Colony counts of microcurette samples from the oral cavity and tongue
      homogenates were used to estimate the effectiveness of four treatment modalities
      to reduce oral fungal burden. All treatment modalities (preventative, premixing
      with the Candida inoculant, drinking water, and treatment) significantly reduced
      fungal burden compared to untreated control animals by day 9; however, the
      preventative and pre-mixing approaches provided a faster rate of fungal
      clearance. The low toxicity and immunogenicity of this synthetic carbohydrate and
      its stability in saliva, as demonstrated by high-performance liquid
      chromatography, make it a promising candidate for the prevention and treatment of
      microbial infections in which the pathogen relies on the beta-GalNAc(1-4)-beta
      galactosidase disaccharide to establish adherence.

PMID- 15980366
TI  - Identical penicillin-binding domains in penicillin-binding proteins of
      Streptococcus pneumoniae clinical isolates with different levels of beta-lactam
      resistance.
AB  - We have sequenced the penicillin-binding domains of the complete repertoire of
      penicillin-binding proteins and MurM from 22 clinical isolates of Streptococcus
      pneumoniae that span a wide range of beta-lactam resistance levels. Evidence of
      mosaicism was found in the genes encoding PBP 1a, PBP 2b, PBP 2x, MurM, and,
      possibly, PBP 2a. Five isolates were found to have identical PBP and MurM
      sequences, even though the MICs for penicillin G ranged from 0.25 to 2.0
      mg/liter. When the sequences encoding PBP 1a, PBP 2b, and PBP 2x from one of
      these isolates were used to transform laboratory strain R6, the resulting strain
      had a resistance level higher than that of the less resistant isolates carrying
      that PBP set but lower than that of the most resistant isolates carrying that PBP
      set. This result demonstrates that if the R6 strain is arbitrarily defined as the
      standard genotype, some wild genetic backgrounds can either increase or decrease
      the PBP-based resistance phenotype.

PMID- 15980367
TI  - Antimicrobial susceptibility of Streptococcus pneumoniae in eight European
      countries from 2001 to 2003.
AB  - Susceptibility testing results for Streptococcus pneumoniae isolates (n = 2,279)
      from eight European countries, examined in the PneumoWorld Study from 2001 to
      2003, are presented. Overall, 24.6% of S. pneumoniae isolates were nonsusceptible
      to penicillin G and 28.0% were resistant to macrolides. The prevalence of
      resistance varied widely between European countries, with the highest rates of
      penicillin G and macrolide resistance reported from Spain and France. Serotype 14
      was the leading serotype among penicillin G- and macrolide-resistant S.
      pneumoniae isolates. One strain (PW 158) showed a combination of an efflux type
      of resistance with a 23S rRNA mutation (A2061G, pneumococcal numbering; A2059G,
      Escherichia coli numbering). Six strains which showed negative results for mef(A)
      and erm(B) in repeated PCR assays had mutations in 23S rRNA or alterations in the
      L4 ribosomal protein (two strains). Fluoroquinolone resistance rates
      (levofloxacin MIC > or = 4 microg/ml) were low (Austria, 0%; Belgium, 0.7%;
      France, 0.9%; Germany, 0.4%; Italy, 1.3%; Portugal, 1.2%; Spain, 1.0%; and
      Switzerland, 0%). Analysis of quinolone resistance-determining regions showed
      eight strains with a Ser81 alteration in gyrA; 13 of 18 strains showed a Ser79
      alteration in parC. The clonal profile, as analyzed by multilocus sequence typing
      (MLST), showed that the 18 fluoroquinolone-resistant strains were genetically
      heterogeneous. Seven of the 18 strains belonged to new sequence types not
      hitherto described in the MLST database. Europe-wide surveillance for monitoring
      of the further spread of these antibiotic-resistant S. pneumoniae clones is
      warranted.

PMID- 15980368
TI  - Antifolate activity of epigallocatechin gallate against Stenotrophomonas
      maltophilia.
AB  - The catechin epigallocatechin gallate, one of the main constituents of green tea,
      showed strong antibiotic activity against 18 isolates of Stenotrophomonas
      maltophilia (MIC range, 4 to 256 microg/ml). In elucidating its mechanism of
      action, we have shown that epigallocatechin gallate is an efficient inhibitor of
      S. maltophilia dihydrofolate reductase, a strategic enzyme that is considered an
      attractive target for the development of antibacterial agents. The inhibition of
      S. maltophilia dihydrofolate reductase by this tea compound was studied and
      compared with the mechanism of a nonclassical antifolate compound, trimethoprim.
      Investigation of dihydrofolate reductase was undertaken with both a trimethoprim
      susceptible S. maltophilia isolate and an isolate with a high level of
      resistance. The enzymes were purified using ammonium sulfate precipitation, gel
      filtration, and methotrexate affinity chromatography. The two isolates showed
      similar levels of dihydrofolate reductase expression and similar substrate
      kinetics. However, the dihydrofolate reductase from the trimethoprim-resistant
      isolate demonstrated decreased susceptibility to inhibition by trimethoprim and
      epigallocatechin gallate. As with other antifolates, the action of
      epigallocatechin gallate was synergistic with that of sulfamethoxazole, a drug
      that blocks folic acid metabolism in bacteria, and the inhibition of bacterial
      growth was attenuated by including leucovorin in the growth medium. We conclude
      that the mechanism of action of epigallocatechin gallate on S. maltophilia is
      related to its antifolate activity.

PMID- 15980369
TI  - Antimicrobial peptide therapeutics for cystic fibrosis.
AB  - Greater than 90% of lung infections in cystic fibrosis (CF) patients are caused
      by Pseudomonas aeruginosa, and the majority of these patients subsequently die
      from lung damage. Current therapies are either targeted at reducing obstruction,
      reducing inflammation, or reducing infection. To identify potential therapeutic
      agents for the CF lung, 150 antimicrobial peptides consisting of three distinct
      structural classes were screened against mucoid and multidrug-resistant clinical
      isolates of P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter
      xylosoxidans, and Staphylococcus aureus. Five peptides that retained potent
      antimicrobial activities in physiological salt and divalent cation environment
      were further characterized in vivo using a rat chronic lung infection model. All
      animals were inoculated intratracheally with 10(4) P. aeruginosa mucoid PAO1
      cells in agar beads. Three days following inoculation treatment was initiated.
      Animals were treated daily for 3 days with 100 microl of peptide solution (1
      mg/ml) in 10 mM sodium citrate, which was deposited via either intratracheal
      instillation or aerosolization. Control animals received daily exposure to
      vehicle alone. At the end of the treatment the lungs of the animals were removed
      for quantitative culture. Four peptides, HBCM2, HBCM3, HBCPalpha-2, and HB71,
      demonstrated significant reduction in Pseudomonas bioburden in the lung of rats.
      Further in vivo studies provided direct evidence that anti-inflammatory activity
      was associated with three of these peptides. Therefore, small bioactive peptides
      have the potential to attack two of the components responsible for the
      progression of lung damage in the CF disease: infection and inflammation.

PMID- 15980370
TI  - Evaluation of a new line probe assay for rapid identification of gyrA mutations
      in Mycobacterium tuberculosis.
AB  - Resistance of Mycobacterium tuberculosis to fluoroquinolones (FQ) results mostly
      from mutations in the gyrA gene. We developed a reverse hybridization-based line
      probe assay in which oligonucleotide probes carrying the wild-type gyrA sequence,
      a serine-to-threonine (S95T) polymorphism, and gyrA mutations (A90V, A90V-S95T,
      S91P, S91P-S95T, D94A, D94N, D94G-S95T, D94H-S95T) were immobilized on
      nitrocellulose strips and hybridized with digoxigenin-labeled PCR products
      obtained from M. tuberculosis strains. When a mutated PCR product was used,
      hybridization occurred to the corresponding mutated probe but not to the wild
      type probe. A panel of M. tuberculosis complex strains including 19 ofloxacin
      resistant (OFL-R) and 9 ofloxacin-susceptible (OFL-S) M. tuberculosis strains was
      studied for detection and identification of gyrA mutations by the line probe
      assay and nucleotide sequencing, in comparison with testing of in vitro
      susceptibility to FQ. Results were 100% concordant with those of nucleotide
      sequencing. The S95T polymorphism, which is not related to FQ resistance, was
      found in 5 OFL-S and 2 OFL-R strains; the other 17 OFL-R strains harbored single
      mutations associated with serine or threonine at codon 95. No mutations were
      found in the other OFL-S strains. Overall, on the basis of the MICs on solid
      medium, the new line probe assay correctly identified all OFL-S and 17 out of 19
      (89.5%) OFL-R strains. A nested-PCR protocol was also evaluated for the assay to
      amplify PCR products from M. tuberculosis-spiked sputa, with a good specificity
      and a sensitivity of 2 x 10(3) M. tuberculosis CFU per ml of sputum.

PMID- 15980371
TI  - Phage P68 virion-associated protein 17 displays activity against clinical
      isolates of Staphylococcus aureus.
AB  - Phage-encoded murein hydrolases are either part of the lysis cassette or found as
      structural components of the phage virion. Here, we show that Staphylococcus
      aureus bacteriophage P68 contains a virion-associated muralytic enzyme. Protein
      17 has a composite structure. The N-terminal part comprises the muralytic
      activity, whereas the C-terminal part is required for binding to the cell
      surface. A high multiplicity of infection with phage P68 caused rapid lysis, and
      purified protein 17 triggered premature lysis when added to S. aureus cells prior
      to infection with P68, suggesting that it functions to weaken the murein at the
      site of phage DNA entry. Protein 17 displayed activity against clinical S. aureus
      isolates, which are resistant to infection by phage P68, demonstrating that the
      protein targets surface structures distinct from the phage receptor. This broad
      activity spectrum of protein 17 could qualify virion-associated muralytic enzymes
      as attractive antimicrobials.

PMID- 15980372
TI  - Identification of a new allelic variant of the Acinetobacter baumannii
      cephalosporinase, ADC-7 beta-lactamase: defining a unique family of class C
      enzymes.
AB  - Acinetobacter spp. are emerging as opportunistic hospital pathogens that
      demonstrate resistance to many classes of antibiotics. In a metropolitan hospital
      in Cleveland, a clinical isolate of Acinetobacter baumannii that tested resistant
      to cefepime and ceftazidime (MIC = 32 microg/ml) was identified. Herein, we
      sought to determine the molecular basis for the extended-spectrum-cephalosporin
      resistance. Using analytical isoelectric focusing, a beta-lactamase with a pI of
      > or = 9.2 was detected. PCR amplification with specific A. baumannii
      cephalosporinase primers yielded a 1,152-bp product which, when sequenced,
      identified a novel 383-amino-acid class C enzyme. Expressed in Escherichia coli
      DH10B, this beta-lactamase demonstrated greater resistance against ceftazidime
      and cefotaxime than cefepime (4.0 microg/ml versus 0.06 microg/ml). The kinetic
      characteristics of this beta-lactamase were similar to other cephalosporinases
      found in Acinetobacter spp. In addition, this cephalosporinase was inhibited by
      meropenem, imipenem, ertapenem, and sulopenem (K(i) < 40 microM). The amino acid
      compositions of this novel enzyme and other class C beta-lactamases thus far
      described for A. baumannii, Acinetobacter genomic species 3, and Oligella
      urethralis in Europe and South Africa suggest that this cephalosporinase defines
      a unique family of class C enzymes. We propose a uniform designation for this
      family of cephalosporinases (Acinetobacter-derived cephalosporinases [ADC]) found
      in Acinetobacter spp. and identify this enzyme as ADC-7 beta-lactamase. The
      coalescence of Acinetobacter ampC beta-lactamases into a single common ancestor
      and the substantial phylogenetic distance separating them from other ampC genes
      support the logical value of developing a system of nomenclature for these
      Acinetobacter cephalosporinase genes.

PMID- 15980373
TI  - Worldwide disseminated armA aminoglycoside resistance methylase gene is borne by
      composite transposon Tn1548.
AB  - The armA (aminoglycoside resistance methylase) gene, which confers resistance to
      4,6-disubstituted deoxystreptamines and fortimicin, was initially found in
      Klebsiella pneumoniae BM4536 on IncL/M plasmid pIP1204 of ca. 90 kb which also
      encodes the extended-spectrum beta-lactamase CTX-M-3. Thirty-four enterobacteria
      from various countries that were likely to produce a CTX-M enzyme since they were
      more resistant to cefotaxime than to ceftazidime were studied. The armA gene was
      detected in 12 clinical isolates of Citrobacter freundii, Enterobacter cloacae,
      Escherichia coli, K. pneumoniae, Salmonella enterica, and Shigella flexneri, in
      which it was always associated with bla(CTX-M-3) on an IncL/M plasmid.
      Conjugation, analysis of DNA sequences, PCR mapping, and plasmid conduction
      experiments indicated that the armA gene was part of composite transposon Tn1548
      together with genes ant3"9, sul1, and dfrXII, which are responsible for
      resistance to streptomycin-spectinomycin, sulfonamides, and trimethoprim,
      respectively. The 16.6-kb genetic element was flanked by two copies of IS6 and
      migrated by replicative transposition. This observation accounts for the presence
      of armA on self-transferable plasmids of various incompatibility groups and its
      worldwide dissemination. It thus appears that posttranscriptional modification of
      16S rRNA confers high-level resistance to all the clinically available
      aminoglycosides except streptomycin in gram-negative human and animal pathogens.

PMID- 15980374
TI  - Mechanisms of resistance to imipenem and ampicillin in Enterococcus faecalis.
AB  - We found ampicillin- and imipenem-resistant isolates of vanA-possessing
      Enterococcus faecalis with MICs of 8 to 16 microg/ml and 4 to 32 microg/ml,
      respectively. There have been few reports about penicillin- and imipenem
      resistant E. faecalis. Two mechanisms of beta-lactam resistance in E. faecalis,
      the production of beta-lactamase and the overproduction of penicillin-binding
      proteins (PBPs), have been reported. The resistant isolates in the current study
      did not produce any beta-lactamases and analysis of the PBPs showed no
      overproduction. However, the affinities of PBP4 for beta-lactams in the resistant
      strains were lower than those of susceptible strains but the affinities of other
      PBPs for beta-lactams did not change. Accordingly, whole pbp4 fragments from
      these resistant isolates were sequenced. Two amino acid substitutions at
      positions 520 and 605 were observed in the highly resistant strains compared to
      the susceptible ones, Pro520Ser and Tyr605His, and a single Tyr605His amino acid
      substitution was found in the low-resistance strains. These two point mutations
      exist in the region between the active-site-defining motifs SDN and KTG of the
      penicillin-binding domain, the main target of beta-lactams. A strong correlation
      was seen between these substitutions and decreasing affinities of PBP4 to beta
      lactams. In E. faecalis, resistance due to mutations in PBPs has not been
      reported, though it has in Enterococcus faecium. Our results suggest that
      development of high-level resistance to penicillins and imipenem depends on point
      mutations of PBP4 at positions 520 and 605.

PMID- 15980375
TI  - In vitro synergy of ciprofloxacin and gatifloxacin against ciprofloxacin
      resistant Pseudomonas aeruginosa.
AB  - Multidrug-resistant Pseudomonas aeruginosa with combined decreased susceptibility
      to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being
      found as a cause of nosocomial infections. It is important to look for
      combinations of drugs that might be synergistic. Ciprofloxacin resistance by P.
      aeruginosa is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8
      methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in
      vitro study using an Etest synergy method and time-kill assay suggested synergy
      of ciprofloxacin and gatifloxacin against P. aeruginosa. Synergy testing was
      performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA
      distinct, U.S. P. aeruginosa isolates. Etest MICs for ciprofloxacin were 4 to >32
      microg/ml, and for gatifloxacin they were >32 microg/ml. Ciprofloxacin plus
      gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31 P.
      aeruginosa isolates using a summation fractional inhibitory concentration of < or
      = 0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time
      kill assay. No antagonism was detected. The remaining isolates were indifferent
      to the combination. The Etest method and time-kill assay were 65% (20/31)
      concordant. The mechanism of the in vitro synergy may include P. aeruginosa
      ciprofloxacin efflux pump inhibition by gatifloxacin.

PMID- 15980376
TI  - Structural and functional study of the phenicol-specific efflux pump FloR
      belonging to the major facilitator superfamily.
AB  - The florfenicol-chloramphenicol resistance gene floR from Salmonella enterica was
      previously identified and postulated to belong to the major facilitator (MF)
      superfamily of drug exporters. Here, we confirmed a computer-predicted
      transmembrane topological model of FloR, using the phoA gene fusion method, and
      classified this protein in the DHA12 family (containing 12 transmembrane domains)
      of MF efflux transporters. We also showed that FloR is a transporter specific for
      structurally associated phenicol drugs (chloramphenicol, florfenicol,
      thiamphenicol) which utilizes the proton motive force to energize an active
      efflux mechanism. By site-directed mutagenesis of specific charged residues
      belonging to putative transmembrane segments (TMS), two residues essential for
      active efflux function, D23 in TMS1 and R109 in TMS4, were identified. Of these,
      the acidic residue D23 seems to participate directly in the affinity pocket
      involved in phenicol derivative recognition. A third residue, E283 in TMS9, seems
      to be necessary for correct membrane folding of the transporter.

PMID- 15980377
TI  - Peptides selected for binding to a virulent strain of Haemophilus influenzae by
      phage display are bactericidal.
AB  - Nontypeable Haemophilus influenzae (NTHi) is an obligate parasite of the
      oropharynx of humans, in whom it commonly causes mucosal infections such as
      otitis media, sinusitis, and bronchitis. We used a subtractive phage display
      approach to affinity select for peptides binding to the cell surface of a novel
      invasive NTHi strain R2866 (also called Int1). Over half of the selected phage
      peptides tested were bactericidal toward R2866 in a dose-dependent manner. Five
      of the clones encoded the same peptide sequence (KQRTSIRATEGCLPS; clone hi3/17),
      while the remaining four clones encoded unique peptides. All of the bactericidal
      phage peptides but one were cationic and had similar physical-chemical
      properties. Clone hi3/17 possessed a similar level of activity toward a panel of
      clinical NTHi isolates and H. influenzae type b strains but lacked bactericidal
      activity toward gram-positive (Enterococcus faecalis, Staphylococcus aureus) and
      gram-negative (Proteus mirabilis, Pseudomonas aeruginosa, and Salmonella
      enterica) bacteria. These data indicate that peptides binding to bacterial
      surface structures isolated by phage display may prove of value in developing new
      antibiotics.

PMID- 15980378
TI  - Mutagenesis analysis of a conserved region involved in acetyl coenzyme A binding
      in the aminoglycoside 6'-N-acetyltransferase type Ib encoded by plasmid pJHCMW1.
AB  - Alanine scanning of motif A in the pJHCMW1-encoded aminoglycoside 6'-N
      acetyltransferase type Ib identified amino acids important for the ability of the
      enzyme to confer wild-type levels of resistance to kanamycin and amikacin. The
      replacement of two amino acids, D117 or L120, with alanine residues resulted in
      complete loss of the resistance phenotype.

PMID- 15980379
TI  - Antimalarial activity of human immunodeficiency virus type 1 protease inhibitors.
AB  - Aspartic proteases play key roles in the biology of malaria parasites and human
      immunodeficiency virus type 1 (HIV-1). We tested the activity of seven HIV-1
      protease inhibitors against cultured Plasmodium falciparum. All compounds
      inhibited the development of parasites at pharmacologically relevant
      concentrations. The most potent compound, lopinavir, was active against parasites
      (50% inhibitory concentration [IC50], 0.9 to 2.1 microM) at concentrations well
      below those achieved by ritonavir-boosted lopinavir therapy. Lopinavir also
      inhibited the P. falciparum aspartic protease plasmepsin II at a similar
      concentration (IC50, 2.7 microM). These findings suggest that use of HIV-1
      protease inhibitors may offer clinically relevant antimalarial activity.

PMID- 15980380
TI  - The macrolide roxithromycin impairs NADPH oxidase activation and alters
      translocation of its cytosolic components to the neutrophil membrane in vitro.
AB  - We have studied the interference of roxithromycin with NADPH oxidase, the key
      enzymatic system for oxidant production by human neutrophils. Roxithromycin
      alters the reconstitution of an active enzyme and impairs the translocation to
      the outer membrane of the cytosolic components p47-phox and p67-phox.
      Interestingly, in resting cells roxithromycin directly triggers the translocation
      of these factors without stimulating the oxidative burst.

PMID- 15980381
TI  - Association between resistance to erythromycin and the presence of the
      fibronectin binding protein F1 gene, prtF1, in Streptococcus pyogenes isolates
      from German pediatric patients.
AB  - A total of 301 German pediatric group A streptococcus isolates were screened for
      the presence of macrolide resistance and the fibronectin binding protein F1 gene
      (prtF1) encoding an adhesin and cell invasiveness protein. The prtF1 gene was
      present significantly more often among macrolide-resistant isolates. The majority
      of these were not clonally related.

PMID- 15980382
TI  - In vitro interactions of micafungin with other antifungal drugs against clinical
      isolates of four species of Cryptococcus.
AB  - The combination of micafungin (MFG) with amphotericin B (AMB), fluconazole,
      itraconazole, voriconazole, or ravuconazole was evaluated against 37 strains of
      four species of Cryptococcus by the checkerboard method. Antagonism was never
      seen. Synergy was observed for some isolates for each combination and was most
      frequent with MFG-AMB.

PMID- 15980383
TI  - In vitro antimicrobial susceptibility testing of Helicobacter felis, H.
      bizzozeronii, and H. salomonis.
AB  - The susceptibilities of Helicobacter felis (15 strains), H. bizzozeronii (7
      strains), and H. salomonis (3 strains) to 10 antimicrobial agents were
      investigated by determination of the MIC using the agar dilution method. No
      consistent differences were noticed between the different Helicobacter species,
      which were all highly susceptible to ampicillin, clarithromycin, tetracycline,
      tylosin, enrofloxacin, gentamicin, and neomycin, as demonstrated by low MICs.
      Higher MICs were obtained for lincomycin (up to 8 microg/ml) and spectinomycin
      (up to 4 microg/ml). Two H. felis strains showed a MIC of 16 microg/ml for
      metronidazole, suggesting acquired resistance to this antimicrobial agent.

PMID- 15980384
TI  - Broader distribution of plasmid-mediated quinolone resistance in the United
      States.
AB  - The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone
      resistance, facilitating selection of higher-level resistance. Epidemiologic
      surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone
      susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone
      susceptible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71
      ceftazidime-resistant Enterobacter strains from across the United States. One of
      these Enterobacter isolates was quinolone susceptible. Thus, qnrA is present in
      quinolone-resistant and quinolone-susceptible Enterobacter and Klebsiella strains
      in the United States.

PMID- 15980386
TI  - Compound efflux in Helicobacter pylori.
AB  - Susceptibility testing with a variety of structurally unrelated compounds showed
      that hefC in Helicobacter pylori is involved in multidrug efflux. This efflux was
      shown to depend on the proton motive force, as demonstrated by ethidium bromide
      accumulation experiments. Thus, H. pylori contains an active multidrug efflux
      mechanism.

PMID- 15980385
TI  - Production of enterocin P, an antilisterial pediocin-like bacteriocin from
      Enterococcus faecium P13, in Pichia pastoris.
AB  - The gene encoding mature enterocin P (EntP), an antimicrobial peptide from
      Enterococcus faecium P13, was cloned into the pPICZalphaA expression vector to
      generate plasmid pJC31. This plasmid was integrated into the genome of P.
      pastoris X-33, and EntP was heterologously secreted from the recombinant P.
      pastoris X-33t1 derivative at a higher production and antagonistic activity than
      from E. faecium P13.

PMID- 15980387
TI  - Time-kill study of the activity of telithromycin against macrolide-resistant
      Streptococcus pneumoniae Isolates with 23S rRNA mutations and changes in
      ribosomal proteins L4 and L22.
AB  - By use of a time-kill methodology, the antipneumococcal activity of telithromycin
      was determined against macrolide-resistant S. pneumoniae isolates having
      mutations in the 23S rRNA gene and changes in the ribosomal proteins L4 and L22.
      Telithromycin had MICs ranging between 0.03 and 0.25 microg/ml and was
      bactericidal against four of seven strains after 24 h at two times the MIC.

PMID- 15980388
TI  - Transcriptional analysis of the bla(CTX-M-2) gene in Salmonella enterica serovar
      Infantis.
AB  - Transcriptional organization of bla(CTX-M-2) present in a multiresistance plasmid
      of Salmonella enterica serovar Infantis suggests the presence of more than one
      promoter involved in the expression of the beta-lactamase gene. At least two
      bla(CTX-M-2)-specific mRNAs (near to 1 kb and 5 kb) were evidenced. Two +1
      signals were detected at -22 bp and -59 bp of bla(CTX-M-2) defining two putative
      promoters.

PMID- 15980389
TI  - Emergence of KPC-possessing Klebsiella pneumoniae in Brooklyn, New York:
      epidemiology and recommendations for detection.
AB  - Among 257 isolates of Klebsiella pneumoniae collected in Brooklyn, NY, 24% were
      found to possess bla(KPC). Clinical microbiology laboratories that used automated
      broth microdilution systems reported 15% of the KPC-possessing isolates as
      susceptible to imipenem. The imipenem MIC was found to be markedly affected by
      the inoculum. For accurate detection of KPC-possessing K. pneumoniae, particular
      attention should be paid to proper inoculum preparation for broth-based
      susceptibility methods. In addition, using ertapenem or meropenem for class
      reporting of carbapenem susceptibility will improve detection.

PMID- 15980390
TI  - Progressive increase in antimicrobial resistance among invasive isolates of
      Haemophilus influenzae obtained from children admitted to a hospital in Kilifi,
      Kenya, from 1994 to 2002.
AB  - Etest susceptibilities to amoxicillin, chloramphenicol, and trimethoprim
      sulfamethoxazole of 240 invasive isolates of Haemophilus influenzae cultured from
      children in rural Kenya were 66%, 66%, and 38%, respectively. Resistance
      increased markedly over 9 years and was concentrated among serotype b isolates.
      In Africa, the increasing cost of treating resistant infections supports economic
      arguments for prevention through conjugate H. influenzae type b immunization.

PMID- 15980391
TI  - In vitro and in vivo bactericidal activities of vancomycin dispersed in porous
      biodegradable poly(epsilon-caprolactone) microparticles.
AB  - Treatment of methicillin-resistant Staphylococcus aureus osteomyelitis requires a
      prolonged antibiotic therapy with vancomycin. Because of its weak diffusion, the
      in situ implantation of vancomycin could be interesting. The activity of
      vancomycin encapsulated in microparticles was evaluated in vitro and in vivo on
      rabbit osteomyelitis and showed a good activity compared to intravenous
      administration.

PMID- 15980392
TI  - Efficacy of nebulized liposomal amphotericin B in treatment of experimental
      pulmonary aspergillosis.
AB  - The efficacy of therapeutic aerosolized amphotericin B (AMB) was studied in a
      steroid-immunosuppressed murine model of invasive pulmonary aspergillosis.
      Nebulized liposomal AMB can be a valid approach to the treatment of this
      infection, with subjects showing significantly improved survival relative to that
      of subjects given intravenous deoxycholate AMB, as well as lower lung weights and
      pulmonary glucosamine levels.

PMID- 15980393
TI  - Predominance of 23S rRNA mutants among non-erm, non-mef macrolide-resistant
      clinical isolates of Streptococcus pneumoniae collected in the United States in
      1999-2000.
AB  - A total of 322 erythromycin-resistant pneumococci from TRUST 3 and TRUST 4 United
      States surveillance studies (1999-2000) were screened for 23S rRNA, L4, and L22
      gene mutations. Nineteen isolates, two with mefA, had mutations at position 2058
      or 2059 in 23S rRNA. Two had a 69GTG71-to-TPS substitution in L4; one of these
      also contained ermA.

PMID- 15980394
TI  - In vitro activity of an oral streptogramin antimicrobial, XRP2868, against gram
      positive bacteria.
AB  - The comparative in vitro potency of XRP2868, a new oral semisynthetic
      streptogramin antibiotic, was evaluated against gram-positive bacteria. XRP2868
      inhibited all staphylococci at < or = 1 microg/ml and all non-pneumococcal
      streptococci at < or = 0.25 microg/ml and was fourfold more potent than
      quinupristin-dalfopristin against Staphylococcus aureus and Enterococcus faecium.

PMID- 15980395
TI  - In vitro antibacterial activity of DX-619, a novel des-fluoro(6) quinolone.
AB  - The in vitro activities of DX-619, des-fluoro(6) quinolone, against 1,208
      clinical isolates were examined. DX-619 was particularly potent against
      staphylococci, including ciprofloxacin- and methicillin-resistant strains; the
      MIC at which 90% of the strains tested were inhibited was 0.5 microg/ml. In
      addition, DX-619 was also active against gram-negative bacteria.

PMID- 15980396
TI  - Novel spectinomycin/streptomycin resistance gene, aadA14, from Pasteurella
      multocida.
AB  - A novel spectinomycin/streptomycin resistance gene, designated aadA14, was
      detected on the mobilizable 5,198-bp plasmid pCCK647 from Pasteurella multocida.
      The aadA14 gene encodes an aminoglycoside adenylyltransferase of 261 amino acids.
      Sequence comparisons revealed that the AadA14 protein showed less than 60%
      identity to the AadA proteins known so far.

PMID- 15980397
TI  - Interaction of the plasmid-encoded quinolone resistance protein QnrA with
      Escherichia coli topoisomerase IV.
AB  - Purified QnrA blocked ciprofloxacin inhibition of topoisomerase IV, just as QnrA
      was previously found to prevent quinolone inhibition of DNA gyrase. With a gel
      displacement assay, tagged QnrA was shown to bind to topoisomerase IV and its
      subunits in a reaction that did not depend on the presence of DNA, quinolone, or
      ATP.

PMID- 15980398
TI  - Prevention of the cryptic epitope SLAYGLR within osteopontin does not influence
      susceptibility to Candida albicans infection.
AB  - The effect of an antiosteopontin antibody (M5 Ab) reacting with the SLAYGLR
      sequence within osteopontin on the host susceptibility to infection was
      investigated in a murine model of disseminated candidiasis. The treatment with
      anti-tumor necrosis factor alpha antibody enhanced fungal infection, while the
      treatment with M5 Ab did not affect the infection.

PMID- 15980399
TI  - In vitro activities of levofloxacin and comparable agents against middle ear
      fluid, nasopharyngeal, and oropharyngeal pathogens obtained from Costa Rican
      children with recurrent otitis media or failing other antibiotic therapy.
AB  - This study analyzes the in vitro activities of levofloxacin and other commonly
      used antimicrobials against middle ear fluid, nasopharyngeal, and oropharyngeal
      pathogens obtained from children with otitis media at risk of having a resistant
      pathogen. Levofloxacin proved to be very active against these pathogens and had
      intermediate activity against Streptococcus pyogenes.

PMID- 15980400
TI  - Induction of telithromycin resistance by erythromycin in isolates of macrolide
      resistant Staphylococcus spp.
AB  - Staphylococcal isolates were examined for possible macrolide-inducible resistance
      to telithromycin. All macrolide-resistant isolates demonstrated telithromycin D
      shaped zones. This result did not discriminate between resistance due to an
      efflux mechanism (msrA) or a ribosomal target modification (ermA or ermC).
      Inducible telithromycin resistance in staphylococci does not appear to be
      analogous to inducible clindamycin resistance.

PMID- 15980401
TI  - Integron-associated antibiotic resistance and phylogenetic grouping of
      Escherichia coli isolates from healthy subjects free of recent antibiotic
      exposure.
AB  - The study of integrons in 181 Escherichia coli isolates from three groups of
      healthy subjects who lived in communities and had not taken antibiotics for at
      least 1 month showed that the presence of integrons was associated with
      antibiotic resistance and phylogenetic grouping of the bacterial host and
      dependent on a subject's living environment.

PMID- 15980402
TI  - Survey of Enterobacteriaceae producing extended-spectrum beta-lactamases in a
      Slovak hospital: dominance of SHV-2a and characterization of TEM-132.
AB  - Eighty-five extended-spectrum beta-lactamase-producing Enterobacteriaceae from a
      Slovak hospital have been studied. SHV-2a was predominant, but other variants
      have been detected, namely, SHV-5, SHV-12, TEM-12, TEM-15, and TEM-132, which
      differed from TEM-1 by amino acid substitutions R164H, E240K, and I173V and had
      kinetic properties similar to those of TEM-28.

PMID- 15980403
TI  - Differences in the DNA sequences in the upstream attenuator region of erm(A) in
      clinical isolates of Streptococcus pyogenes and their correlation with
      macrolide/lincosamide resistance.
AB  - The regulatory regions of 52 erm(A) [formerly erm(TR)] clinical Streptococcus
      pyogenes isolates were studied. Differences in the upstream regulatory region of
      erm(A) correlated with macrolide/lincosamide resistance patterns. Nine
      macrolide/lincosamide/streptogramin B-resistant isolates had changes in the
      leader sequence of erm(A) including base changes, insertions, or deletions.
      Isolates were also emm typed.

PMID- 15980404
TI  - Molecular characterization of glycopeptide-resistant Enterococcus faecium
      isolates from Portuguese hospitals.
AB  - Fifty-one pulsed-field gel electrophoresis types and 17 Tn1546 variants were
      identified among 101 Enterococcus faecium isolates recovered in three distant
      Portuguese hospitals. Intra- and interhospital dissemination of specific strains
      and Tn1546 types was detected, which might largely contribute to the endemicity
      of vancomycin-resistant E. faecium in Portuguese hospitals, as happened
      previously in other geographical locations.

PMID- 15980405
TI  - Heterogeneity of genotype-phenotype correlation among macrolide-resistant
      Streptococcus agalactiae isolates.
AB  - Seventy-four erythromycin-resistant group B Streptococcus isolates were analyzed
      regarding their phenotype-genotype and phenotype-serotype correlation. Four
      different phenotypes were assessed, one of them for the first time. ermB and
      ermTR were the most frequent genotypes (80%). The most prevalent serotype III
      showed great phenotypic variability while serotype V was strongly associated only
      with two different phenotypes.

PMID- 15980406
TI  - Cooperative uptake of microcin E492 by receptors FepA, Fiu, and Cir and
      inhibition by the siderophore enterochelin and its dimeric and trimeric
      hydrolysis products.
AB  - Microcin E492 uptake by FepA, Fiu, and Cir is cooperative, with FepA being the
      main receptor. No TonB-mediated interaction with the ferric catecholate receptors
      is needed for microcin to exert action at the cytoplasmic membrane. Microcin E492
      uptake by the receptors is inhibited by the dimer and trimer of
      dihydroxybenzoylserine.

PMID- 15980407
TI  - Sublethal concentrations of ciprofloxacin induce bacteriocin synthesis in
      Escherichia coli.
AB  - Antibiotics that interfere with DNA replication, as well as cell wall synthesis,
      induce the SOS response. In this report, we show that ciprofloxacin induces
      synthesis of colicins, narrow-spectrum antibiotics frequently produced by
      Escherichia coli strains, in an SOS-dependent manner.

PMID- 15980408
TI  - Association of plasmid-mediated quinolone resistance with extended-spectrum beta
      lactamase VEB-1.
AB  - Association of the plasmid-mediated quinolone resistance determinant QnrA and the
      bla(VEB-1) gene was identified in a single Enterobacter cloacae isolate from K.
      Bicetre, France, and in 11 out of 23 bla(VEB-1)-positive enterobacterial isolates
      from Bangkok, Thailand. This result may explain in part the association between
      quinolone and extended-spectrum beta-lactam resistance.

PMID- 15980409
TI  - Specific antibodies, levofloxacin, and modulation of capsule-associated virulence
      in Streptococcus pneumoniae.

PMID- 15980410
TI  - One new LEN enzyme and two new OKP enzymes in Klebsiella pneumoniae clinical
      isolates and proposed nomenclature for chromosomal beta-lactamases of this
      species.

PMID- 15980411
TI  - Tet protein hybrids.

PMID- 15980413
TI  - Long chain CoA esters as competitive antagonists of phosphatidylinositol 4,5
      bisphosphate activation in Kir channels.
AB  - Long chain fatty acid esters of coenzyme A (LC-CoA) are potent activators of ATP
      sensitive (K(ATP)) channels, and elevated levels have been implicated in the
      pathophysiology of type 2 diabetes. This stimulatory effect is thought to involve
      a mechanism similar to phosphatidylinositol 4,5-bisphosphate (PIP2), which
      activates all known inwardly rectifying potassium (Kir) channels. However, the
      effect of LC-CoA on other Kir channels has not been well characterized. In this
      study, we show that in contrast to their stimulatory effect on K(ATP) channels,
      LC-CoA (e.g. oleoyl-CoA) potently and reversibly inhibits all other Kir channels
      tested (Kir1.1, Kir2.1, Kir3.4, Kir7.1). We also demonstrate that the inhibitory
      potency of the LC-CoA increases with the chain length of the fatty acid chain,
      while both its activatory and inhibitory effects critically depend on the
      presence of the 3'-ribose phosphate on the CoA group. Biochemical studies also
      demonstrate that PIP2 and LC-CoA bind with similar affinity to the C-terminal
      domains of Kir2.1 and Kir6.2 and that PIP2 binding can be competitively
      antagonized by LC-CoA, suggesting that the mechanism of LC-CoA inhibition
      involves displacement of PIP2. Furthermore, we demonstrate that in contrast to
      its stimulatory effect on K(ATP) channels, phosphatidylinositol 3,4-bisphosphate
      has an inhibitory effect on Kir1.1 and Kir2.1. These results demonstrate a bi
      directional modulation of Kir channel activity by LC-CoA and phosphoinositides
      and suggest that changes in fatty acid metabolism (e.g. LC-CoA production) could
      have profound and widespread effects on cellular electrical activity.

PMID- 15980414
TI  - Identification of two critical amino acid residues of the severe acute
      respiratory syndrome coronavirus spike protein for its variation in zoonotic
      tropism transition via a double substitution strategy.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified
      human coronavirus. The extremely high homology of the viral genomic sequences
      between the viruses isolated from human (huSARS-CoV) and those of palm civet
      origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic
      analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was
      subjected to the strongest positive selection pressure during transmission, and
      there were six amino acid residues within the receptor-binding domain of the S
      protein being potentially important for SARS progression and tropism. Using the
      single-round infection assay, we found that a two-amino acid substitution
      (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its
      infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon
      the infection of mouse ACE2 cells. Although single substitution of these two
      residues had no effects on the infectivity of huSARS-CoV, these recombinant S
      proteins bound to human ACE2 with different levels of reduced affinity, and the
      two-amino acid-substituted S protein showed extremely low affinity. On the
      contrary, substitution of these two amino acid residues of pcSARS-CoV for those
      of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells.
      These results suggest that amino acid residues at position 479 and 487 of the S
      protein are important determinants for SARS-CoV tropism and animal-to-human
      transmission.

PMID- 15980415
TI  - Ubiquitination of p27Kip1 requires physical interaction with cyclin E and
      probable phosphate recognition by SKP2.
AB  - p27Kip1 is an essential cell cycle inhibitor of Cyclin-dependent kinases.
      Ubiquitin-mediated proteolysis of p27Kip1 is an important mechanism for
      activation of Cyclin E-Cdk2 and facilitates G1/S transition. Ubiquitination of
      p27 is primarily catalyzed by a multisubunit E3 ubiquitin ligase, SCF(Skp2), and
      requires an adapter protein Cks1. In addition, phosphorylation of p27 at Thr187
      by Cyclin E and Cdk2 is also essential for triggering substrate ubiquitination.
      Here we investigate the molecular mechanism of p27 ubiquitination. We show that
      Cyclin E-Cdk2 is essential for targeting the p27 substrate to SCF(Skp2). Direct
      physical contact between Cyclin E but not Cdk2 and p27 is required for p27
      recruitment to SCF(Skp2). In a search for positively charged amino acid residues
      that may be involved in recognition of the Thr187 phosphate group, we found that
      Arg306 of Skp2 is required for association and ubiquitination of phosphorylated
      p27 but dispensable for ubiquitination of unphosphorylated p21. Thus, our data
      unravel the molecular organization of the ubiquitination complex that catalyzes
      p27 ubiquitination and provide unique insights into the specificity of substrate
      recognition by SCF(Skp2).

PMID- 15980416
TI  - Doctor of nursing practice--MRI or total body scan?

PMID- 15980418
TI  - Family types in the neurotrauma intensive care unit.

PMID- 15980419
TI  - Understanding treatment-seeking delay in women with acute myocardial infarction:
      descriptions of decision-making patterns.
AB  - BACKGROUND: Women delay seeking treatment for symptoms of acute myocardial
      infarction longer than men delay. Women's delay time has not been thoroughly
      characterized. OBJECTIVES: To qualitatively describe the period between the onset
      of symptoms of myocardial infarction and enactment of the decision to seek care
      (decision time) and to identify common patterns of cognitive, affective, and
      behavioral responses to the symptoms (decision trajectories). METHODS: In this
      qualitative study, 52 women were asked in semistructured interviews to describe
      the symptoms and related thoughts, decisions, and actions from the onset of
      symptoms of myocardial infarction to arrival at the hospital. Narrative analysis
      was used to examine the stories and to identify patterns of decision-making
      behavior. RESULTS: Six common patterns of behavior during the decision time were
      identified: knowing and going, knowing and letting someone take over, knowing and
      going on the patient's own terms, knowing and waiting, managing an alternative
      hypothesis, and minimizing. The patterns were further grouped as knowing or
      managing. Women in the 2 groups (knowing and managing) differed primarily in
      their awareness and interpretations of the symptoms and in their patterns of
      behavior in seeking treatment. CONCLUSIONS: Women's delay in seeking treatment
      for symptoms of myocardial infarction can be categorized into distinct patterns.
      Clinicians can use knowledge of these patterns to detect responses and situations
      that can decrease decision time in future cardiac events and to educate women
      about how to respond to cardiac symptoms.

PMID- 15980420
TI  - Psychosocial issues of patients with implantable cardioverter defibrillators.
AB  - Use of implantable cardioverter defibrillators has become standard therapy for
      patients at high risk for life-threatening ventricular arrhythmias. Although
      acceptance of the device is generally high among patients and their families,
      quality of life and psychosocial issues associated with use of the defibrillators
      deserve greater attention to improve outcomes. Psychosocial issues, their
      ramifications, and theory-and evidence-based approaches to improving outcomes are
      described.

PMID- 15980421
TI  - Hand hygiene behavior in a pediatric emergency department and a pediatric
      intensive care unit: comparison of use of 2 dispenser systems.
AB  - BACKGROUND: Adherence to hand hygiene standards is poor. Approaches and systems
      to improve hand hygiene practices warrant testing. OBJECTIVE: To compare the
      frequency of use of manually operated and touch-free dispensers of sanitizer for
      hand hygiene. METHODS: Manual and touch-free dispensers of alcohol sanitizer were
      placed in the emergency department and an intensive care unit of a large
      pediatric hospital for two 2-month periods for each type of dispenser. Counting
      devices installed in each dispenser and direct observations were used to
      determine actual frequency of and indications for hand hygiene. RESULTS: The
      touch-free dispensers were used significantly more often than were the manual
      dispensers. The means for the number of episodes of hand hygiene per hour were
      4.42 for the touch-free dispensers and 3.33 for the manual dispensers (P=.04);
      the means for the number of episodes per patient per hour were 2.22 and 1.79,
      respectively (P=.004); and the means for the number of uses of the dispenser per
      day were 41.2 and 25.6, respectively (P=.02). However, the overall compliance
      rate was 38.4% (2136 episodes of hand hygiene per 5568 indications for hand
      hygiene). CONCLUSIONS: The type of dispensing system influenced hand hygiene
      behavior. Nevertheless, overall hand hygiene compliance remained low. In order
      for interventions to have a major effect on hand hygiene, multiple factors must
      be considered.

PMID- 15980422
TI  - An acute myocardial infarction?

PMID- 15980423
TI  - Depression, healing, and recovery from coronary artery bypass surgery.
AB  - BACKGROUND: Effects of postoperative depression on recovery from coronary artery
      bypass grafting have not been widely studied. OBJECTIVES: To evaluate emotional
      and physical recovery after bypass surgery and investigate associations between
      depressive symptoms and infections and impaired wound healing in patients with
      high and low levels of depressive symptoms. METHODS: A nonrandomized,
      comparative, longitudinal design was used to study 72 bypass surgery patients
      without serious noncardiac comorbidities who were available for follow-up after
      discharge. Patients completed questionnaires to assess depressive symptoms,
      emotional recovery, and physical recovery within 48 hours after extubation, at
      discharge from the hospital, and 6 weeks later and performed 6-minute walk tests
      at the last 2 times. Infections and impaired wound healing (as indicated by
      positive cultures, antibiotic treatment, or extra treatments, such as
      debridements or incisions and drainage) were identified by chart audit. RESULTS:
      At discharge, patients with higher depressive symptom scores (indicating more
      symptoms) reported poorer emotional recovery (P<.001) and poorer physical
      recovery (P=.007) and achieved shorter walking distances (P<.001) than did
      patients with lower scores (indicating fewer symptoms). Six weeks after
      discharge, emotional and physical recovery remained lower in patients with more
      depressive symptoms (P<.001). Infections and impaired wound healing were more
      common among patients with higher depressive symptom scores (46%) than among
      patients with lower scores (19%, P=.03). CONCLUSIONS: After bypass surgery,
      depressive symptoms are associated with infections, impaired wound healing, and
      poor emotional and physical recovery.

PMID- 15980424
TI  - Effect of backrest elevation on the development of ventilator-associated
      pneumonia.
AB  - BACKGROUND: Ventilator-associated pneumonia is a common complication of
      mechanical ventilation. Backrest position and time spent supine are critical risk
      factors for aspiration, increasing the risk for pneumonia. Empirical evidence of
      the effect of backrest positions on the incidence of ventilator-associated
      pneumonia, especially during mechanical ventilation over time, is limited.
      OBJECTIVE: To describe the relationship between backrest elevation and
      development of ventilator-associated pneumonia. METHODS: A nonexperimental,
      longitudinal, descriptive design was used. The Clinical Pulmonary Infection Score
      was used to determine ventilator-associated pneumonia. Backrest elevation was
      measured continuously with a transducer system. Data were obtained from
      laboratory results and medical records from the start of mechanical ventilation
      up to 7 days. RESULTS: Sixty-six subjects were monitored (276 patient days). Mean
      backrest elevation for the entire study period was 21.7 degrees . Backrest
      elevations were less than 30 degrees 72% of the time and less than 10 degrees 39%
      of the time. The mean Clinical Pulmonary Infection Score increased but not
      significantly, and backrest elevation had no direct effect on mean scores. A
      model for predicting the Clinical Pulmonary Infection Score at day 4 included
      baseline score, percentage of time spent at less than 30 degrees on study day 1,
      and score on the Acute Physiology and Chronic Health Evaluation II, explaining
      81% of the variability (F=7.31, P=.003). CONCLUSIONS: Subjects spent the majority
      of the time at backrest elevations less than 30 degrees . Only the combination of
      early, low backrest elevation and severity of illness affected the incidence of
      ventilator-associated pneumonia.

PMID- 15980425
TI  - Boundaries of double effect.

PMID- 15980426
TI  - Statin therapy in congestive heart failure.

PMID- 15980427
TI  - ST segment changes in right bundle branch block.

PMID- 15980429
TI  - Myosin V from Drosophila reveals diversity of motor mechanisms within the myosin
      V family.
AB  - Myosin V is the best characterized vesicle transporter in vertebrates, but it has
      been unknown as to whether all members of the myosin V family share a common,
      evolutionarily conserved mechanism of action. Here we show that myosin V from
      Drosophila has a strikingly different motor mechanism from that of vertebrate
      myosin Va, and it is a nonprocessive, ensemble motor. Our steady-state and
      transient kinetic measurements on single-headed constructs reveal that a single
      Drosophila myosin V molecule spends most of its mechanochemical cycle time
      detached from actin, therefore it has to function in processive units that
      comprise several molecules. Accordingly, in in vitro motility assays, double
      headed Drosophila myosin V requires high surface concentrations to exhibit a
      continuous translocation of actin filaments. Our comparison between vertebrate
      and fly myosin V demonstrates that the well preserved function of myosin V motors
      in cytoplasmic transport can be accomplished by markedly different underlying
      mechanisms.

PMID- 15980428
TI  - Connexin 43 interacts with zona occludens-1 and -2 proteins in a cell cycle stage
      specific manner.
AB  - Gap junction channels play an important role in cell growth control, secretion
      and embryonic development. Gap junctional communication and channel assembly can
      be regulated by protein-protein interaction with kinases and phosphatases. We
      have utilized tandem mass spectrometry (MS/MS) sequence analysis as a screen to
      identify proteins from cell lysates that interact with the C-terminal cytoplasmic
      region of connexin 43 (Cx43). MS/MS analysis of tryptic fragments yielded several
      proteins including zona occludens-1 (ZO-1), a structural protein previously
      identified to interact with Cx43, and ZO-2, a potential novel interacting
      partner. We confirmed the interaction of ZO-2 with Cx43 by using a combination of
      fusion protein "pull down," co-immunoprecipitation, and co-localization
      experiments. We show that the C-terminal region of Cx43 is necessary for
      interaction with the PDZ2 domain of ZO-2. Far Western analysis revealed that ZO-2
      can directly bind to Cx43 independent of other interacting partners.
      Immunofluorescence studies indicate that both ZO-1 and ZO-2 can co-localize with
      Cx43 within the plasma membrane at apparent gap junctional structures. We
      examined Cx43 interaction with ZO-1 and ZO-2 at different stages of the cell
      cycle and found that Cx43 had a strong preference for interaction with ZO-1
      during G0, whereas ZO-2 interaction occurred approximately equally during G0 and
      S phases. Since essentially all of the Cx43 in G0 cells is assembled into Triton
      X-100-resistant junctions, Cx43-ZO-1 interaction may contribute to their
      stability.

PMID- 15980430
TI  - Transforming growth factor-beta1-induced expression of smooth muscle marker genes
      involves activation of PKN and p38 MAPK.
AB  - Differentiated vascular smooth muscle cells (SMCs) exhibit a work phenotype
      characterized by expression of several well documented contractile apparatus
      associated proteins. However, SMCs retain the ability to de-differentiate into a
      proliferative phenotype, which is involved in the progression of vascular
      diseases such as atherosclerosis and restenosis. Understanding the mechanisms
      involved in maintaining SMC differentiation is critical for preventing
      proliferation associated with vascular disease. In this study, the molecular
      mechanisms through which transforming growth factor-beta1 (TGF-beta1) induces
      differentiation of SMCs were examined. TGF-beta1 stimulated actin re
      organization, inhibited cell proliferation, and up-regulated SMC marker gene
      expression in PAC-1 SMCs. These effects were blocked by pretreatment of cells
      with either HA1077 or Y-27632, which inhibit the kinases downstream of RhoA.
      Moreover, TGF-beta1 activated RhoA and its downstream target PKN. Overexpression
      of active PKN alone was sufficient to increase the transcriptional activity of
      the promoters that control expression of smooth muscle (SM) alpha-actin, SM
      myosin heavy chain, and SM22alpha. In addition, PKN increased the activities of
      serum-response factor (SRF), GATA, and MEF2-dependent enhancer-reporters. RNA
      interference-mediated inhibition of PKN abolished TGF-beta1-induced activation of
      SMC marker gene promoters. Finally, examination of MAPK signaling demonstrated
      that TGF-beta1 increased the activity of p38 MAPK, which was required for
      activation of the SMC marker gene promoters. Co-expression of dominant negative
      p38 MAPK was sufficient to block PKN-mediated activation of the SMC marker gene
      promoters as well as the serum-response factor, GATA, and MEF2 enhancers. Taken
      together, these results identify components of an important intracellular
      signaling pathway through which TGF-beta1 activates PKN to promote
      differentiation of SMCs.

PMID- 15980431
TI  - Loop 1 of transducer region in mammalian class I myosin, Myo1b, modulates actin
      affinity, ATPase activity, and nucleotide access.
AB  - Loop 1, a flexible surface loop in the myosin motor domain, comprises in part the
      transducer region that lies near the nucleotide-binding site and is proposed from
      structural studies to be responsible for the kinetic tuning of product release
      following ATP hydrolysis (1). Biochemical studies have shown that loop 1 affects
      the affinity of actin-myosin-II for ADP, motility and the V(max) of the actin
      activated Mg2+-ATPase activity, possibly through P(i) release (2-8). To test the
      influence of loop 1 on the mammalian class I myosin, Myo1b, chimeric molecules in
      which (i) loop 1 of a truncated form of Myo1b, Myo1b1IQ, was replaced with either
      loop 1 from other myosins; (ii) loop 1 was replaced with glycine; or (iii) some
      amino acids in the loop were substituted with alanine and were expressed in
      baculovirus, and their interactions with actin and nucleotide were evaluated. The
      steady-state actin-activated ATPase activity; rate of ATP-induced dissociation of
      actin from Myo1b1IQ; rate of ADP release from actin-Myo1b1IQ; and the affinity of
      actin for Myo1b1IQ and Myo1b1IQ.ADP differed in the chimeras versus wild type,
      indicating that loop 1 has a much wider range of effects on the coupling between
      actin and nucleotide binding events than previously thought. In particular, the
      biphasic ATP-induced dissociation of actin from actin-Myo1b1IQ was significantly
      altered in the chimeras. This provided evidence that loop 1 contributes to the
      accessibility of the nucleotide pocket and is involved in the integration of
      information from the actin-, nucleotide-, gamma-P(i)-, and calmodulin-binding
      sites and predicts that loop 1 modulates the load dependence of the motor.

PMID- 15980432
TI  - Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by
      calmodulin and Ca2+-binding protein-1.
AB  - Ca(2+)-binding protein-1 (CaBP1) and calmodulin (CaM) are highly related Ca(2+)
      binding proteins that directly interact with, and yet differentially regulate,
      voltage-gated Ca(2+) channels. Whereas CaM enhances inactivation of Ca(2+)
      currents through Ca(v)1.2 (L-type) Ca(2+) channels, CaBP1 completely prevents
      this process. How CaBP1 and CaM mediate such opposing effects on Ca(v)1.2
      inactivation is unknown. Here, we identified molecular determinants in the
      alpha(1)-subunit of Ca(v)1.2 (alpha(1)1.2) that distinguish the effects of CaBP1
      and CaM on inactivation. Although both proteins bind to a well characterized IQ
      domain in the cytoplasmic C-terminal domain of alpha(1)1.2, mutations of the IQ
      domain that significantly weakened CaM and CaBP1 binding abolished the functional
      effects of CaM, but not CaBP1. Pulldown binding assays revealed Ca(2+)
      independent binding of CaBP1 to the N-terminal domain (NT) of alpha(1)1.2, which
      was in contrast to Ca(2+)-dependent binding of CaM to this region. Deletion of
      the NT abolished the effects of CaBP1 in prolonging Ca(v)1.2 Ca(2+) currents, but
      spared Ca(2+)-dependent inactivation due to CaM. We conclude that the NT and IQ
      domains of alpha(1)1.2 mediate functionally distinct interactions with CaBP1 and
      CaM that promote conformational alterations that either stabilize or inhibit
      inactivation of Ca(v)1.2.

PMID- 15980433
TI  - G alpha12 interaction with alphaSNAP induces VE-cadherin localization at
      endothelial junctions and regulates barrier function.
AB  - The involvement of heterotrimeric G proteins in the regulation of adherens
      junction function is unclear. We identified alphaSNAP as an interactive partner
      of G alpha12 using yeast two-hybrid screening. Glutathione S-transferase pull
      down assays showed the selective interaction of alphaSNAP with G alpha12 in COS-7
      as well as in human umbilical vein endothelial cells. Using domain swapping
      experiments, we demonstrated that the N-terminal region of G alpha12 (1-37 amino
      acids) was necessary and sufficient for its interaction with alphaSNAP. G alpha13
      with its N-terminal extension replaced by that of G alpha12 acquired the ability
      to bind to alphaSNAP, whereas G alpha12 with its N terminus replaced by that of G
      alpha13 lost this ability. Using four point mutants of alphaSNAP, which alter its
      ability to bind to the SNARE complex, we determined that the convex rather than
      the concave surface of alphaSNAP was involved in its interaction with G alpha12.
      Co-transfection of human umbilical vein endothelial cells with G alpha12 and
      alphaSNAP stabilized VE-cadherin at the plasma membrane, whereas down-regulation
      of alphaSNAP with siRNA resulted in the loss of VE-cadherin from the cell surface
      and, when used in conjunction with G alpha12 overexpression, decreased
      endothelial barrier function. Our results demonstrate a direct link between the
      alpha subunit of G12 and alphaSNAP, an essential component of the membrane fusion
      machinery, and implicate a role for this interaction in regulating the membrane
      localization of VE-cadherin and endothelial barrier function.

PMID- 15980434
TI  - Inhibition of vascular permeability factor/vascular endothelial growth factor
      mediated angiogenesis by the Kruppel-like factor KLF2.
AB  - The Kruppel-like factor KLF2 was recently identified as a novel regulator of
      endothelial pro-inflammatory and pro-thrombotic function. Here it is shown that
      overexpression of KLF2 potently inhibits vascular permeability factor/vascular
      endothelial growth factor (VEGF-A)-mediated angiogenesis and tissue edema in the
      nude ear mouse model of angiogenesis. In vitro, KLF2 expression retards VEGF
      mediated calcium flux, proliferation and induction of pro-inflammatory factors in
      endothelial cells. This effect is due to a potent inhibition of VEGFR2/KDR
      expression and promoter activity. These observations identify KLF2 as a regulator
      of VEGFR2/KDR and provide a foundation for novel approaches to regulate
      angiogenesis.

PMID- 15980436
TI  - LOCSVMPSI: a web server for subcellular localization of eukaryotic proteins using
      SVM and profile of PSI-BLAST.
AB  - Subcellular location of a protein is one of the key functional characters as
      proteins must be localized correctly at the subcellular level to have normal
      biological function. In this paper, a novel method named LOCSVMPSI has been
      introduced, which is based on the support vector machine (SVM) and the position
      specific scoring matrix generated from profiles of PSI-BLAST. With a jackknife
      test on the RH2427 data set, LOCSVMPSI achieved a high overall prediction
      accuracy of 90.2%, which is higher than the prediction results by SubLoc and
      ESLpred on this data set. In addition, prediction performance of LOCSVMPSI was
      evaluated with 5-fold cross validation test on the PK7579 data set and the
      prediction results were consistently better than the previous method based on
      several SVMs using composition of both amino acids and amino acid pairs. Further
      test on the SWISSPROT new-unique data set showed that LOCSVMPSI also performed
      better than some widely used prediction methods, such as PSORTII, TargetP and
      LOCnet. All these results indicate that LOCSVMPSI is a powerful tool for the
      prediction of eukaryotic protein subcellular localization. An online web server
      (current version is 1.3) based on this method has been developed and is freely
      available to both academic and commercial users, which can be accessed by at
      http://Bioinformatics.ustc.edu.cn/LOCSVMPSI/LOCSVMPSI.php.

PMID- 15980437
TI  - AS2TS system for protein structure modeling and analysis.
AB  - We present a set of programs and a website designed to facilitate protein
      structure comparison and protein structure modeling efforts. Our protein
      structure analysis and comparison services use the LGA (local-global alignment)
      program to search for regions of local similarity and to evaluate the level of
      structural similarity between compared protein structures. To facilitate the
      homology-based protein structure modeling process, our AL2TS service translates
      given sequence-structure alignment data into the standard Protein Data Bank (PDB)
      atom records (coordinates). For a given sequence of amino acids, the AS2TS (amino
      acid sequence to tertiary structure) system calculates (e.g. using PSI-BLAST PDB
      analysis) a list of the closest proteins from the PDB, and then a set of draft 3D
      models is automatically created. Web services are available at
      http://as2ts.llnl.gov/.

PMID- 15980438
TI  - InterProScan: protein domains identifier.
AB  - InterProScan [E. M. Zdobnov and R. Apweiler (2001) Bioinformatics, 17, 847-848]
      is a tool that combines different protein signature recognition methods from the
      InterPro [N. J. Mulder, R. Apweiler, T. K. Attwood, A. Bairoch, A. Bateman, D.
      Binns, P. Bradley, P. Bork, P. Bucher, L. Cerutti et al. (2005) Nucleic Acids
      Res., 33, D201-D205] consortium member databases into one resource. At the time
      of writing there are 10 distinct publicly available databases in the application.
      Protein as well as DNA sequences can be analysed. A web-based version is
      accessible for academic and commercial organizations from the EBI
      (http://www.ebi.ac.uk/InterProScan/). In addition, a standalone Perl version and
      a SOAP Web Service [J. Snell, D. Tidwell and P. Kulchenko (2001) Programming Web
      Services with SOAP, 1st edn. O'Reilly Publishers, Sebastopol, CA,
      http://www.w3.org/TR/soap/] are also available to the users. Various output
      formats are supported and include text tables, XML documents, as well as various
      graphs to help interpret the results.

PMID- 15980439
TI  - PhyloDome--visualization of taxonomic distributions of domains occurring in
      eukaryote protein sequence sets.
AB  - The analysis of taxonomic distribution and lineage-specific variation of domains
      and domain combinations is an important step in the assessment of their
      functional roles and potential interoperability. In the study of eukaryote
      sequence sets with many multi-domain proteins, it can become laborious to
      evaluate the phylogenetic context of the many occurring domains and their mutual
      relationships. PhyloDome is an answer to that problem. It provides a fast
      overview on the taxonomic spreading and potential interrelation of domains that
      are either given as a list of names and PFAM/SMART accessions or derived from a
      user-defined set of sequences. This taxonomic distribution analysis can be
      helpful in protein function and interaction assignment as the comparative study
      of potential Hedgehog pathway members in C.elegans shows. An implementation of
      PhyloDome is accessible for public use as a WWW-Service at
      http://mendel.imp.univie.ac.at/phylodome/. Software components are available on
      request.

PMID- 15980440
TI  - PRODOC: a resource for the comparison of tethered protein domain architectures
      with in-built information on remotely related domain families.
AB  - PROtein Domain Organization and Comparison (PRODOC) comprises several programs
      that enable convenient comparison of proteins as a sequence of domains. The in
      built dataset currently consists of approximately 698 000 proteins from 192
      organisms with complete genomic data, and all the SWISSPROT proteins obtained
      from the Pfam database. All the entries in PRODOC are represented as a sequence
      of functional domains, assigned using hidden Markov models, instead of as a
      sequence of amino acids. On average 69% of the proteins in the proteomes and 49%
      of the residues are covered by functional domain assignments. Software tools
      allow the user to query the dataset with a sequence of domains and identify
      proteins with the same or a jumbled or circularly permuted arrangement of
      domains. As it is proposed that proteins with jumbled or the same domain
      sequences have similar functions, this search tool is useful in assigning the
      overall function of a multi-domain protein. Unique features of PRODOC include the
      generation of alignments between multi-domain proteins on the basis of the
      sequence of domains and in-built information on distantly related domain families
      forming superfamilies. It is also possible using PRODOC to identify domain
      sharing and gene fusion events across organisms. An exhaustive genome-genome
      comparison tool in PRODOC also enables the detection of successive domain sharing
      and domain fusion events across two organisms. The tool permits the
      identification of gene clusters involved in similar biological processes in two
      closely related organisms. The URL for PRODOC is
      http://hodgkin.mbu.iisc.ernet.in/~prodoc.

PMID- 15980441
TI  - DIAL: a web-based server for the automatic identification of structural domains
      in proteins.
AB  - DIAL is a web server for the automatic identification of structural domains given
      the 3D coordinates of a protein. Delineation of the structural domains and their
      exact boundaries are the starting points for the better realization of distantly
      related members of the domain families, for the rational design of the
      experiments and for clearer understanding of the biological function. The current
      server can examine crystallographic multiple chains and provide structural domain
      solutions that can also describe domain swapping events. The server can be
      accessed from http://www.ncbs.res.in/~faculty/mini/DIAL/home.html. The
      Supplementary data can be accessed from
      http://www.ncbs.res.in/~faculty/mini/DIAL/supplement.html.

PMID- 15980442
TI  - pdbFun: mass selection and fast comparison of annotated PDB residues.
AB  - pdbFun (http://pdbfun.uniroma2.it) is a web server for structural and functional
      analysis of proteins at the residue level. pdbFun gives fast access to the whole
      Protein Data Bank (PDB) organized as a database of annotated residues. The
      available data (features) range from solvent exposure to ligand binding ability,
      location in a protein cavity, secondary structure, residue type, sequence
      functional pattern, protein domain and catalytic activity. Users can select any
      residue subset (even including any number of PDB structures) by combining the
      available features. Selections can be used as probe and target in multiple
      structure comparison searches. For example a search could involve, as a query,
      all solvent-exposed, hydrophylic residues that are not in alpha-helices and are
      involved in nucleotide binding. Possible examples of targets are represented by
      another selection, a single structure or a dataset composed of many structures.
      The output is a list of aligned structural matches offered in tabular and also
      graphical format.

PMID- 15980443
TI  - PEPVAC: a web server for multi-epitope vaccine development based on the
      prediction of supertypic MHC ligands.
AB  - Prediction of peptide binding to major histocompatibility complex (MHC) molecules
      is a basis for anticipating T-cell epitopes, as well as epitope discovery-driven
      vaccine development. In the human, MHC molecules are known as human leukocyte
      antigens (HLAs) and are extremely polymorphic. HLA polymorphism is the basis of
      differential peptide binding, until now limiting the practical use of current
      epitope-prediction tools for vaccine development. Here, we describe a web server,
      PEPVAC (Promiscuous EPitope-based VACcine), optimized for the formulation of
      multi-epitope vaccines with broad population coverage. This optimization is
      accomplished through the prediction of peptides that bind to several HLA
      molecules with similar peptide-binding specificity (supertypes). Specifically, we
      offer the possibility of identifying promiscuous peptide binders to five distinct
      HLA class I supertypes (A2, A3, B7, A24 and B15). We estimated the phenotypic
      population frequency of these supertypes to be 95%, regardless of ethnicity.
      Targeting these supertypes for promiscuous peptide-binding predictions results in
      a limited number of potential epitopes without compromising the population
      coverage required for practical vaccine design considerations. PEPVAC can also
      identify conserved MHC ligands, as well as those with a C-terminus resulting from
      proteasomal cleavage. The combination of these features with the prediction of
      promiscuous HLA class I ligands further limits the number of potential epitopes.
      The PEPVAC server is hosted by the Dana-Farber Cancer Institute at the site
      http://immunax.dfci.harvard.edu/PEPVAC/.

PMID- 15980444
TI  - GPCRsclass: a web tool for the classification of amine type of G-protein-coupled
      receptors.
AB  - The receptors of amine subfamily are specifically major drug targets for therapy
      of nervous disorders and psychiatric diseases. The recognition of novel amine
      type of receptors and their cognate ligands is of paramount interest for
      pharmaceutical companies. In the past, Chou and co-workers have shown that
      different types of amine receptors are correlated with their amino acid
      composition and are predictable on its basis with considerable accuracy [Elrod
      and Chou (2002) Protein Eng., 15, 713-715]. This motivated us to develop a better
      method for the recognition of novel amine receptors and for their further
      classification. The method was developed on the basis of amino acid composition
      and dipeptide composition of proteins using support vector machine. The method
      was trained and tested on 167 proteins of amine subfamily of G-protein-coupled
      receptors (GPCRs). The method discriminated amine subfamily of GPCRs from
      globular proteins with Matthew's correlation coefficient of 0.98 and 0.99 using
      amino acid composition and dipeptide composition, respectively. In classifying
      different types of amine receptors using amino acid composition and dipeptide
      composition, the method achieved an accuracy of 89.8 and 96.4%, respectively. The
      performance of the method was evaluated using 5-fold cross-validation. The
      dipeptide composition based method predicted 67.6% of protein sequences with an
      accuracy of 100% with a reliability index > or =5. A web server GPCRsclass has
      been developed for predicting amine-binding receptors from its amino acid
      sequence [http://www.imtech.res.in/raghava/gpcrsclass/ and
      http://bioinformatics.uams.edu/raghava/gpersclass/ (mirror site)].

PMID- 15980445
TI  - GRIFFIN: a system for predicting GPCR-G-protein coupling selectivity using a
      support vector machine and a hidden Markov model.
AB  - We describe a novel system, GRIFFIN (G-protein and Receptor Interaction Feature
      Finding INstrument), that predicts G-protein coupled receptor (GPCR) and G
      protein coupling selectivity based on a support vector machine (SVM) and a hidden
      Markov model (HMM) with high sensitivity and specificity. Based on our assumption
      that whole structural segments of ligands, GPCRs and G-proteins are essential to
      determine GPCR and G-protein coupling, various quantitative features were
      selected for ligands, GPCRs and G-protein complex structures, and those
      parameters that are the most effective in selecting G-protein type were used as
      feature vectors in the SVM. The main part of GRIFFIN includes a hierarchical SVM
      classifier using the feature vectors, which is useful for Class A GPCRs, the
      major family. For the opsins and olfactory subfamilies of Class A and other minor
      families (Classes B, C, frizzled and smoothened), the binding G-protein is
      predicted with high accuracy using the HMM. Applying this system to known GPCR
      sequences, each binding G-protein is predicted with high sensitivity and
      specificity (>85% on average). GRIFFIN (http://griffin.cbrc.jp/) is freely
      available and allows users to easily execute this reliable prediction of G
      proteins.

PMID- 15980446
TI  - Scooby-domain: prediction of globular domains in protein sequence.
AB  - Scooby-domain (sequence hydrophobicity predicts domains) is a fast and simple
      method to identify globular domains in protein sequence, based on the observed
      lengths and hydrophobicities of domains from proteins with known tertiary
      structure. The prediction method successfully identifies sequence regions that
      will form a globular structure and those that are likely to be unstructured. The
      method does not rely on homology searches and, therefore, can identify previously
      unknown domains for structural elucidation. Scooby-domain is available as a Java
      applet at http://ibivu.cs.vu.nl/programs/scoobywww. It may be used to visualize
      local properties within a protein sequence, such as average hydrophobicity,
      secondary structure propensity and domain boundaries, as well as being a method
      for fast domain assignment of large sequence sets.

PMID- 15980447
TI  - TMBETA-NET: discrimination and prediction of membrane spanning beta-strands in
      outer membrane proteins.
AB  - We have developed a web-server, TMBETA-NET for discriminating outer membrane
      proteins and predicting their membrane spanning beta-strand segments. The amino
      acid compositions of globular and outer membrane proteins have been
      systematically analyzed and a statistical method has been proposed for
      discriminating outer membrane proteins. The prediction of membrane spanning
      segments is mainly based on feed forward neural network and refined with beta
      strand length. Our program takes the amino acid sequence as input and displays
      the type of the protein along with membrane-spanning beta-strand segments as a
      stretch of highlighted amino acid residues. Further, the probability of residues
      to be in transmembrane beta-strand has been provided with a coloring scheme. We
      observed that outer membrane proteins were discriminated with an accuracy of 89%
      and their membrane spanning beta-strand segments at an accuracy of 73% just from
      amino acid sequence information. The prediction server is available at
      http://psfs.cbrc.jp/tmbeta-net/.

PMID- 15980448
TI  - CEP: a conformational epitope prediction server.
AB  - CEP server (http://bioinfo.ernet.in/cep.htm) provides a web interface to the
      conformational epitope prediction algorithm developed in-house. The algorithm,
      apart from predicting conformational epitopes, also predicts antigenic
      determinants and sequential epitopes. The epitopes are predicted using 3D
      structure data of protein antigens, which can be visualized graphically. The
      algorithm employs structure-based Bioinformatics approach and solvent
      accessibility of amino acids in an explicit manner. Accuracy of the algorithm was
      found to be 75% when evaluated using X-ray crystal structures of Ag-Ab complexes
      available in the PDB. This is the first and the only method available for the
      prediction of conformational epitopes, which is an attempt to map probable
      antibody-binding sites of protein antigens.

PMID- 15980449
TI  - MULTIPRED: a computational system for prediction of promiscuous HLA binding
      peptides.
AB  - MULTIPRED is a web-based computational system for the prediction of peptide
      binding to multiple molecules (proteins) belonging to human leukocyte antigens
      (HLA) class I A2, A3 and class II DR supertypes. It uses hidden Markov models and
      artificial neural network methods as predictive engines. A novel data
      representation method enables MULTIPRED to predict peptides that promiscuously
      bind multiple HLA alleles within one HLA supertype. Extensive testing was
      performed for validation of the prediction models. Testing results show that
      MULTIPRED is both sensitive and specific and it has good predictive ability (area
      under the receiver operating characteristic curve A(ROC) > 0.80). MULTIPRED can
      be used for the mapping of promiscuous T-cell epitopes as well as the regions of
      high concentration of these targets--termed T-cell epitope hotspots. MULTIPRED is
      available at http://antigen.i2r.a-star.edu.sg/multipred/.

PMID- 15980450
TI  - PREDBALB/c: a system for the prediction of peptide binding to H2d molecules, a
      haplotype of the BALB/c mouse.
AB  - PRED(BALB/c) is a computational system that predicts peptides binding to the
      major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important
      laboratory model organism. The predictions include the complete set of H2(d)
      class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d))
      molecules. The prediction system utilizes quantitative matrices, which were
      rigorously validated using experimentally determined binders and non-binders and
      also by in vivo studies using viral proteins. The prediction performance of
      PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online
      server for the prediction of peptides binding to a complete set of major
      histocompatibility complex molecules in a model organism (H2(d) haplotype).
      PRED(BALB/c) is available at http://antigen.i2r.a-star.edu.sg/predBalbc/.

PMID- 15980451
TI  - GPS: a comprehensive www server for phosphorylation sites prediction.
AB  - Protein phosphorylation plays a fundamental role in most of the cellular
      regulatory pathways. Experimental identification of protein kinases' (PKs)
      substrates with their phosphorylation sites is labor-intensive and often limited
      by the availability and optimization of enzymatic reactions. Recently, large
      scale analysis of the phosphoproteome by the mass spectrometry (MS) has become a
      popular approach. But experimentally, it is still difficult to distinguish the
      kinase-specific sites on the substrates. In this regard, the in silico prediction
      of phosphorylation sites with their specific kinases using protein's primary
      sequences may provide guidelines for further experimental consideration and
      interpretation of MS phosphoproteomic data. A variety of such tools exists over
      the Internet and provides the predictions for at most 30 PK subfamilies. We
      downloaded the verified phosphorylation sites from the public databases and
      curated the literature extensively for recently found phosphorylation sites. With
      the hypothesis that PKs in the same subfamily share similar consensus
      sequences/motifs/functional patterns on substrates, we clustered the 216 unique
      PKs in 71 PK groups, according to the BLAST results and protein annotations.
      Then, we applied the group-based phosphorylation scoring (GPS) method on the data
      set; here, we present a comprehensive PK-specific prediction server GPS, which
      could predict kinase-specific phosphorylation sites from protein primary
      sequences for 71 different PK groups. GPS has been implemented in PHP and is
      available on a www server at http://973-proteinweb.ustc.edu.cn/gps/gps_web/.

PMID- 15980452
TI  - TMB-Hunt: a web server to screen sequence sets for transmembrane beta-barrel
      proteins.
AB  - TMB-Hunt is a program that uses a modified k-nearest neighbour (k-NN) algorithm
      to classify protein sequences as transmembrane beta-barrel (TMB) or non-TMB on
      the basis of whole sequence amino acid composition. By including differentially
      weighted amino acids, evolutionary information and by calibrating the scoring, a
      discrimination accuracy of 92.5% was achieved, as tested using a rigorous cross
      validation procedure. The TMB-Hunt web server, available at
      www.bioinformatics.leeds.ac.uk/betaBarrel, allows screening of up to 10,000
      sequences in a single query and provides results and key statistics in a simple
      colour coded format.

PMID- 15980453
TI  - Web-based toolkits for topology prediction of transmembrane helical proteins,
      fold recognition, structure and binding scoring, folding-kinetics analysis and
      comparative analysis of domain combinations.
AB  - We have developed the following web servers for protein structural modeling and
      analysis at http://theory.med.buffalo.edu: THUMBUP, UMDHMM(TMHP) and TUPS,
      predictors of transmembrane helical protein topology based on a mean-burial
      propensity scale of amino acid residues (THUMBUP), hidden Markov model
      (UMDHMM(TMHP)) and their combinations (TUPS); SPARKS 2.0 and SP3, two profile
      profile alignment methods, that match input query sequence(s) to structural
      templates by integrating sequence profile with knowledge-based structural score
      (SPARKS 2.0) and structure-derived profile (SP3); DFIRE, a knowledge-based
      potential for scoring free energy of monomers (DMONOMER), loop conformations
      (DLOOP), mutant stability (DMUTANT) and binding affinity of protein
      protein/peptide/DNA complexes (DCOMPLEX & DDNA); TCD, a program for protein
      folding rate and transition-state analysis of small globular proteins; and DOGMA,
      a web-server that allows comparative analysis of domain combinations between
      plant and other 55 organisms. These servers provide tools for prediction and/or
      analysis of proteins on the secondary structure, tertiary structure and
      interaction levels, respectively.

PMID- 15980454
TI  - TRAMPLE: the transmembrane protein labelling environment.
AB  - TRAMPLE (http://gpcr.biocomp.unibo.it/biodec/) is a web application server
      dedicated to the detection and the annotation of transmembrane protein sequences.
      TRAMPLE includes different state-of-the-art algorithms for the prediction of
      signal peptides, transmembrane segments (both beta-strands and alpha-helices),
      secondary structure and fast fold recognition. TRAMPLE also includes a complete
      content management system to manage the results of the predictions. Each user of
      the server has his/her own workplace, where the data can be stored, organized,
      accessed and annotated with documents through a simple web-based interface. In
      this manner, TRAMPLE significantly improves usability with respect to other more
      traditional web servers.

PMID- 15980455
TI  - GraBCas: a bioinformatics tool for score-based prediction of Caspase- and
      Granzyme B-cleavage sites in protein sequences.
AB  - Caspases and granzyme B are proteases that share the primary specificity to
      cleave at the carboxyl terminal of aspartate residues in their substrates. Both,
      caspases and granzyme B are enzymes that are involved in fundamental cellular
      processes and play a central role in apoptotic cell death. Although various
      targets are described, many substrates still await identification and many
      cleavage sites of known substrates are not identified or experimentally verified.
      A more comprehensive knowledge of caspase and granzyme B substrates is essential
      to understand the biological roles of these enzymes in more detail. The
      relatively high variability in cleavage site recognition sequence often
      complicates the identification of cleavage sites. As of yet there is no software
      available that allows identification of caspase and/or granzyme with cleavage
      sites differing from the consensus sequence. Here, we present a bioinformatics
      tool 'GraBCas' that provides score-based prediction of potential cleavage sites
      for the caspases 1-9 and granzyme B including an estimation of the fragment size.
      We tested GraBCas on already known substrates and showed its usefulness for
      protein sequence analysis. GraBCas is available at http://wwwalt.med-rz.uniklinik
      saarland.de/med_fak/humangenetik/software/index.html.

PMID- 15980456
TI  - GlyProt: in silico glycosylation of proteins.
AB  - GlyProt (http://www.glycosciences.de/glyprot/) is a web-based tool that enables
      meaningful N-glycan conformations to be attached to all the spatially accessible
      potential N-glycosylation sites of a known three-dimensional (3D) protein
      structure. The probabilities of physicochemical properties such as mass,
      accessible surface and radius of gyration are calculated. The purpose of this
      service is to provide rapid access to reliable 3D models of glycoproteins, which
      can subsequently be refined by using more elaborate simulations and validated by
      comparing the generated models with experimental data.

PMID- 15980457
TI  - SEARCHGTr: a program for analysis of glycosyltransferases involved in
      glycosylation of secondary metabolites.
AB  - SEARCHGTr is a web-based software for the analysis of glycosyltransferases (GTrs)
      involved in the biosynthesis of a variety of pharmaceutically important compounds
      like adriamycin, erythromycin, vancomycin etc. This software has been developed
      based on a comprehensive analysis of sequence/structural features of 102 GTrs of
      known specificity from 52 natural product biosynthetic gene clusters. SEARCHGTr
      is a powerful tool that correlates sequences of GTrs to the chemical structures
      of their corresponding substrates. This software indicates the donor/acceptor
      specificity and also identifies putative substrate binding residues. In addition,
      it provides interfaces to other public databases like GENBANK, SWISS-PROT, CAZY,
      PDB, PDBSum and PUBMED for extracting various information on GTrs homologous to
      the query sequence. SEARCHGTr would provide new dimension to our previously
      developed bioinformatics tool NRPS-PKS. Together, these tools facilitate
      comprehensive computational analysis of proteins involved in biosynthesis of
      aglycone core and its downstream glycosylations. Apart from presenting
      opportunities for rational design of novel natural products, these tools would
      assist in the identification of biosynthetic products of secondary metabolite
      gene clusters found in newly sequenced genomes. SEARCHGTr can be accessed at
      http://www.nii.res.in/searchgtr.html.

PMID- 15980458
TI  - KinasePhos: a web tool for identifying protein kinase-specific phosphorylation
      sites.
AB  - KinasePhos is a novel web server for computationally identifying catalytic kinase
      specific phosphorylation sites. The known phosphorylation sites from public
      domain data sources are categorized by their annotated protein kinases. Based on
      the profile hidden Markov model, computational models are learned from the kinase
      specific groups of the phosphorylation sites. After evaluating the learned
      models, the model with highest accuracy was selected from each kinase-specific
      group, for use in a web-based prediction tool for identifying protein
      phosphorylation sites. Therefore, this work developed a kinase-specific
      phosphorylation site prediction tool with both high sensitivity and specificity.
      The prediction tool is freely available at http://KinasePhos.mbc.nctu.edu.tw/.

PMID- 15980459
TI  - DiANNA: a web server for disulfide connectivity prediction.
AB  - Correctly predicting the disulfide bond topology in a protein is of crucial
      importance for the understanding of protein function and can be of great help for
      tertiary prediction methods. The web server
      http://clavius.bc.edu/~clotelab/DiANNA/ outputs the disulfide connectivity
      prediction given input of a protein sequence. The following procedure is
      performed. First, PSIPRED is run to predict the protein's secondary structure,
      then PSIBLAST is run against the non-redundant SwissProt to obtain a multiple
      alignment of the input sequence. The predicted secondary structure and the
      profile arising from this alignment are used in the training phase of our neural
      network. Next, cysteine oxidation state is predicted, then each pair of cysteines
      in the protein sequence is assigned a likelihood of forming a disulfide bond-
      this is performed by means of a novel architecture (diresidue neural network).
      Finally, Rothberg's implementation of Gabow's maximum weighted matching algorithm
      is applied to diresidue neural network scores in order to produce the final
      connectivity prediction. Our novel neural network-based approach achieves results
      that are comparable and in some cases better than the current state-of-the-art
      methods.

PMID- 15980460
TI  - REPPER--repeats and their periodicities in fibrous proteins.
AB  - REPPER (REPeats and their PERiodicities) is an integrated server that detects and
      analyzes regions with short gapless repeats in protein sequences or alignments.
      It finds periodicities by Fourier Transform (FTwin) and internal similarity
      analysis (REPwin). FTwin assigns numerical values to amino acids that reflect
      certain properties, for instance hydrophobicity, and gives information on
      corresponding periodicities. REPwin uses self-alignments and displays repeats
      that reveal significant internal similarities. Both programs use a sliding window
      to ensure that different periodic regions within the same protein are detected
      independently. FTwin and REPwin are complemented by secondary structure
      prediction (PSIPRED) and coiled coil prediction (COILS), making the server a
      versatile analysis tool for sequences of fibrous proteins. REPPER is available at
      http://protevo.eb.tuebingen.mpg.de/repper.

PMID- 15980461
TI  - The HHpred interactive server for protein homology detection and structure
      prediction.
AB  - HHpred is a fast server for remote protein homology detection and structure
      prediction and is the first to implement pairwise comparison of profile hidden
      Markov models (HMMs). It allows to search a wide choice of databases, such as the
      PDB, SCOP, Pfam, SMART, COGs and CDD. It accepts a single query sequence or a
      multiple alignment as input. Within only a few minutes it returns the search
      results in a user-friendly format similar to that of PSI-BLAST. Search options
      include local or global alignment and scoring secondary structure similarity.
      HHpred can produce pairwise query-template alignments, multiple alignments of the
      query with a set of templates selected from the search results, as well as 3D
      structural models that are calculated by the MODELLER software from these
      alignments. A detailed help facility is available. As a demonstration, we analyze
      the sequence of SpoVT, a transcriptional regulator from Bacillus subtilis. HHpred
      can be accessed at http://protevo.eb.tuebingen.mpg.de/hhpred.

PMID- 15980462
TI  - Fragnostic: walking through protein structure space.
AB  - The Fragnostic (http://ffas.burnham.org/Fragnostic) web tool implements a novel
      and useful view of protein structure space. We mined a non-redundant subset of
      the PDB for common fragments shared between proteins inhabiting different SCOP
      folds. Subsequently, we formulated an inter-fold similarity measure based on
      fragment sharing. Fold space is described as a graph whose nodes are folds
      between which the edges are drawn depending on the extent of fragment sharing. In
      this fashion, Fragnostic helps discover meaningful relationships between proteins
      belonging to different folds, based on sharing similar fragments in the proteins
      comprising those folds. Distant fold similarity information is supplemented by
      annotations taken from Gene Ontology, SCOP and CATH. Overall, Fragnostic is a
      tool which helps discover structural and functional relationships between
      proteins which are distantly related or seemingly unrelated.

PMID- 15980463
TI  - SOAP-based services provided by the European Bioinformatics Institute.
AB  - SOAP (Simple Object Access Protocol) (http://www.w3.org/TR/soap) based Web
      Services technology (http://www.w3.org/ws) has gained much attention as an open
      standard enabling interoperability among applications across heterogeneous
      architectures and different networks. The European Bioinformatics Institute (EBI)
      is using this technology to provide robust data retrieval and data analysis
      mechanisms to the scientific community and to enhance utilization of the
      biological resources it already provides [N. Harte, V. Silventoinen, E.
      Quevillon, S. Robinson, K. Kallio, X. Fustero, P. Patel, P. Jokinen and R. Lopez
      (2004) Nucleic Acids Res., 32, 3-9]. These services are available free to all
      users from http://www.ebi.ac.uk/Tools/webservices.

PMID- 15980464
TI  - CX, DPX and PRIDE: WWW servers for the analysis and comparison of protein 3D
      structures.
AB  - The WWW servers at http://www.icgeb.org/protein/ are dedicated to the analysis of
      protein 3D structures submitted by the users as the Protein Data Bank (PDB)
      files. CX computes an atomic protrusion index that makes it possible to highlight
      the protruding atoms within a protein 3D structure. DPX calculates a depth index
      for the buried atoms and makes it possible to analyze the distribution of buried
      residues. CX and DPX return PDB files containing the calculated indices that can
      then be visualized using standard programs, such as Swiss-PDBviewer and Rasmol.
      PRIDE compares 3D structures using a fast algorithm based on the distribution of
      inter-atomic distances. The options include pairwise as well as multiple
      comparisons, and fold recognition based on searching the CATH fold database.

PMID- 15980465
TI  - QuasiMotiFinder: protein annotation by searching for evolutionarily conserved
      motif-like patterns.
AB  - Sequence signature databases such as PROSITE, which include amino acid segments
      that are indicative of a protein's function, are useful for protein annotation.
      Lamentably, the annotation is not always accurate. A signature may be falsely
      detected in a protein that does not carry out the associated function (false
      positive prediction, FP) or may be overlooked in a protein that does carry out
      the function (false negative prediction, FN). A new approach has emerged in which
      a signature is replaced with a sequence profile, calculated based on multiple
      sequence alignment (MSA) of homologous proteins that share the same function.
      This approach, which is superior to the simple pattern search, essentially
      searches with the sequence of the query protein against an MSA library. We
      suggest here an alternative approach, implemented in the QuasiMotiFinder web
      server (http://quasimotifinder.tau.ac.il/), which is based on a search with an
      MSA of homologous query proteins against the original PROSITE signatures. The
      explicit use of the average evolutionary conservation of the signature in the
      query proteins significantly reduces the rate of FP prediction compared with the
      simple pattern search. QuasiMotiFinder also has a reduced rate of FN prediction
      compared with simple pattern searches, since the traditional search for precise
      signatures has been replaced by a permissive search for signature-like patterns
      that are physicochemically similar to known signatures. Overall, QuasiMotiFinder
      and the profile search are comparable to each other in terms of performance. They
      are also complementary to each other in that signatures that are falsely detected
      in (or overlooked by) one may be correctly detected by the other.

PMID- 15980466
TI  - PatMatch: a program for finding patterns in peptide and nucleotide sequences.
AB  - Here, we present PatMatch, an efficient, web-based pattern-matching program that
      enables searches for short nucleotide or peptide sequences such as cis-elements
      in nucleotide sequences or small domains and motifs in protein sequences. The
      program can be used to find matches to a user-specified sequence pattern that can
      be described using ambiguous sequence codes and a powerful and flexible pattern
      syntax based on regular expressions. A recent upgrade has improved performance
      and now supports both mismatches and wildcards in a single pattern. This
      enhancement has been achieved by replacing the previous searching algorithm,
      scan_for_matches [D'Souza et al. (1997), Trends in Genetics, 13, 497-498], with
      nondeterministic-reverse grep (NR-grep), a general pattern matching tool that
      allows for approximate string matching [Navarro (2001), Software Practice and
      Experience, 31, 1265-1312]. We have tailored NR-grep to be used for DNA and
      protein searches with PatMatch. The stand-alone version of the software can be
      adapted for use with any sequence dataset and is available for download at The
      Arabidopsis Information Resource (TAIR) at
      ftp://ftp.arabidopsis.org/home/tair/Software/Patmatch/. The PatMatch server is
      available on the web at http://www.arabidopsis.org/cgi-bin/patmatch/nph
      patmatch.pl for searching Arabidopsis thaliana sequences.

PMID- 15980467
TI  - MINER: software for phylogenetic motif identification.
AB  - MINER is web-based software for phylogenetic motif (PM) identification. PMs are
      sequence regions (fragments) that conserve the overall familial phylogeny. PMs
      have been shown to correspond to a wide variety of catalytic regions, substrate
      binding sites and protein interfaces, making them ideal functional site
      predictions. The MINER output provides an intuitive interface for interactive PM
      sequence analysis and structural visualization. The web implementation of MINER
      is freely available at http://www.pmap.csupomona.edu/MINER/. Source code is
      available to the academic community on request.

PMID- 15980468
TI  - SCANMOT: searching for similar sequences using a simultaneous scan of multiple
      sequence motifs.
AB  - Establishment of similarities between proteins is very important for the study of
      the relationship between sequence, structure and function and for the analysis of
      evolutionary relationships. Motif-based search methods play a crucial role in
      establishing the connections between proteins that are particularly useful for
      distant relationships. This paper reports SCANMOT, a web-based server that
      searches for similarities between proteins by simultaneous matching of multiple
      motifs. SCANMOT searches for similar sequences in entire sequence databases using
      multiple conserved regions and utilizes inter-motif spacing as restraints. The
      SCANMOT server is available via
      http://www.ncbs.res.in/~faculty/mini/scanmot/scanmot.html.

PMID- 15980469
TI  - ProTeus: identifying signatures in protein termini.
AB  - ProTeus (PROtein TErminUS) is a web-based tool for the identification of short
      linear signatures in protein termini. It is based on a position-based search
      method for revealing short signatures in termini of all proteins. The initial
      step in ProTeus development was to collect all signature groups (SIGs) based on
      their relative positions at the termini. The initial set of SIGs went through a
      sequential process of inspection and removal of SIGs, which did not meet the
      attributed statistical thresholds. The SIGs that were found significant represent
      protein sets with minimal or no overall sequence similarity besides the
      similarity found at the termini. These SIGs were archived and are presented at
      ProTeus. The SIGs are sorted by their strong correspondence to functional
      annotation from external databases such as GO. ProTeus provides rich search and
      visualization tools for evaluating the quality of different SIGs. A search option
      allows the identification of terminal signatures in new sequences. ProTeus (ver
      1.2) is available at http://www.proteus.cs.huji.ac.il.

PMID- 15980470
TI  - One-Block CYRCA: an automated procedure for identifying multiple-block alignments
      from single block queries.
AB  - One-Block CYRCA is an automated procedure for identifying multiple-block
      alignments from single block queries
      (http://bioinfo.weizmann.ac.il/blocks/OneCYRCA). It is based on the LAMA and
      CYRCA block-to-block alignment methods. The procedure identifies whether the
      query blocks can form new multiple-block alignments (block sets) with blocks from
      a database or join pre-existing database block sets. Using pre-computed LAMA
      block alignments and CYRCA sets from the Blocks database reduces the computation
      time. LAMA and CYRCA are highly sensitive and selective methods that can augment
      many other sequence analysis approaches.

PMID- 15980471
TI  - FFAS03: a server for profile--profile sequence alignments.
AB  - The FFAS03 server provides a web interface to the third generation of the profile
      profile alignment and fold-recognition algorithm of fold and function assignment
      system (FFAS) [L. Rychlewski, L. Jaroszewski, W. Li and A. Godzik (2000), Protein
      Sci., 9, 232-241]. Profile-profile algorithms use information present in
      sequences of homologous proteins to amplify the patterns defining the family. As
      a result, they enable detection of remote homologies beyond the reach of other
      methods. FFAS, initially developed in 2000, is consistently one of the best
      ranked fold prediction methods in the CAFASP and LiveBench competitions. It is
      also used by several fold-recognition consensus methods and meta-servers. The
      FFAS03 server accepts a user supplied protein sequence and automatically
      generates a profile, which is then compared with several sets of sequence
      profiles of proteins from PDB, COG, PFAM and SCOP. The profile databases used by
      the server are automatically updated with the latest structural and sequence
      information. The server provides access to the alignment analysis, multiple
      alignment, and comparative modeling tools. Access to the server is open for both
      academic and commercial researchers. The FFAS03 server is available at
      http://ffas.burnham.org.

PMID- 15980472
TI  - PRALINE: a multiple sequence alignment toolbox that integrates homology-extended
      and secondary structure information.
AB  - PRofile ALIgNEment (PRALINE) is a fully customizable multiple sequence alignment
      application. In addition to a number of available alignment strategies, PRALINE
      can integrate information from database homology searches to generate a homology
      extended multiple alignment. PRALINE also provides a choice of seven different
      secondary structure prediction programs that can be used individually or in
      combination as a consensus for integrating structural information into the
      alignment process. The program can be used through two separate interfaces: one
      has been designed to cater to more advanced needs of researchers in the field,
      and the other for standard construction of high confidence alignments. The web
      based output is designed to facilitate the comprehensive visualization of the
      generated alignments by means of five default colour schemes based on: residue
      type, position conservation, position reliability, residue hydrophobicity and
      secondary structure, depending on the options set. A user can also define a
      custom colour scheme by selecting which colour will represent one or more amino
      acids in the alignment. All generated alignments are also made available in the
      PDF format for easy figure generation for publications. The grouping of
      sequences, on which the alignment is based, can also be visualized as a
      dendrogram. PRALINE is available at http://ibivu.cs.vu.nl/programs/pralinewww/.

PMID- 15980473
TI  - The Diamond STING server.
AB  - Diamond STING is a new version of the STING suite of programs for a comprehensive
      analysis of a relationship between protein sequence, structure, function and
      stability. We have added a number of new functionalities by both providing more
      structure parameters to the STING Database and by improving/expanding the
      interface for enhanced data handling. The integration among the STING components
      has also been improved. A new key feature is the ability of the STING server to
      handle local files containing protein structures (either modeled or not yet
      deposited to the Protein Data Bank) so that they can be used by the principal
      STING components: (Java)Protein Dossier ((J)PD) and STING Report. The current
      capabilities of the new STING version and a couple of biologically relevant
      applications are described here. We have provided an example where Diamond STING
      identifies the active site amino acids and folding essential amino acids (both
      previously determined by experiments) by filtering out all but those residues by
      selecting the numerical values/ranges for a set of corresponding parameters. This
      is the fundamental step toward a more interesting endeavor-the prediction of such
      residues. Diamond STING is freely accessible at http://sms.cbi.cnptia.embrapa.br
      and http://trantor.bioc.columbia.edu/SMS.

PMID- 15980474
TI  - Manipulating multiple sequence alignments via MaM and WebMaM.
AB  - MaM is a software tool that processes and manipulates multiple alignments of
      genomic sequence. MaM computes the exact location of common repeat elements,
      exons and unique regions within aligned genomics sequences using a variety of
      user identified programs, databases and/or tables. The program can extract
      subalignments, corresponding to these various regions of DNA to be analyzed
      independently or in conjunction with other elements of genomic DNA. Graphical
      displays further allow an assessment of sequence variation throughout these
      different regions of the aligned sequence, providing separate displays for their
      repeat, non-repeat and coding portions of genomic DNA. The program should
      facilitate the phylogenetic analysis and processing of different portions of
      genomic sequence as part of large-scale sequencing efforts. MaM source code is
      freely available for non-commercial use at http://compbio.cs.sfu.ca/MAM.htm; and
      the web interface WebMaM is hosted at http://atgc.lirmm.fr/mam.

PMID- 15980475
TI  - ConSurf 2005: the projection of evolutionary conservation scores of residues on
      protein structures.
AB  - Key amino acid positions that are important for maintaining the 3D structure of a
      protein and/or its function(s), e.g. catalytic activity, binding to ligand, DNA
      or other proteins, are often under strong evolutionary constraints. Thus, the
      biological importance of a residue often correlates with its level of
      evolutionary conservation within the protein family. ConSurf
      (http://consurf.tau.ac.il/) is a web-based tool that automatically calculates
      evolutionary conservation scores and maps them on protein structures via a user
      friendly interface. Structurally and functionally important regions in the
      protein typically appear as patches of evolutionarily conserved residues that are
      spatially close to each other. We present here version 3.0 of ConSurf. This new
      version includes an empirical Bayesian method for scoring conservation, which is
      more accurate than the maximum-likelihood method that was used in the earlier
      release. Various additional steps in the calculation can now be controlled by a
      number of advanced options, thus further improving the accuracy of the
      calculation. Moreover, ConSurf version 3.0 also includes a measure of confidence
      for the inferred amino acid conservation scores.

PMID- 15980476
TI  - The Bioinformatics Links Directory: a compilation of molecular biology web
      servers.
AB  - The Bioinformatics Links Directory is an online community resource that contains
      a directory of freely available tools, databases, and resources for
      bioinformatics and molecular biology research. The listing of the servers
      published in this and previous issues of Nucleic Acids Research together with
      other useful tools and websites represents a rich repository of resources that
      are openly provided to the research community using internet technologies. The
      166 servers highlighted in the 2005 90002 are included in the more than 700 links
      to useful online resources that are currently contained within the descriptive
      biological categories of the Bioinformatics Links Directory. This curated listing
      of bioinformatics resources is available online at the Bioinformatics Links
      Directory web site, http://bioinformatics.ubc.ca/resources/links_directory/. A
      complete listing of the 2005 Nucleic Acids Research 90002 servers is available
      online at the Nucleic Acids web site, http://nar.oupjournals.org/, and on the
      Bioinformatics Links Directory web site,
      http://bioinformatics.ubc.ca/resources/links_directory/narweb2005/.

PMID- 15980477
TI  - SRide: a server for identifying stabilizing residues in proteins.
AB  - Residues expected to play key roles in the stabilization of proteins [stabilizing
      residues (SRs)] are selected by combining several methods based mainly on the
      interactions of a given residue with its spatial, rather than its sequential
      neighborhood and by considering the evolutionary conservation of the residues. A
      residue is selected as a stabilizing residue if it has high surrounding
      hydrophobicity, high long-range order, high conservation score and if it belongs
      to a stabilization center. The definition of all these parameters and the
      thresholds used to identify the SRs are discussed in detail. The algorithm for
      identifying SRs was originally developed for TIM-barrel proteins [M. M. Gromiha,
      G. Pujadas, C. Magyar, S. Selvaraj, and I. Simon (2004), Proteins, 55, 316-329]
      and is now generalized for all proteins of known 3D structure. SRs could be
      applied in protein engineering and homology modeling and could also help to
      explain certain folds with significant stability. The SRide server is located at
      http://sride.enzim.hu.

PMID- 15980478
TI  - I-Mutant2.0: predicting stability changes upon mutation from the protein sequence
      or structure.
AB  - I-Mutant2.0 is a support vector machine (SVM)-based tool for the automatic
      prediction of protein stability changes upon single point mutations. I-Mutant2.0
      predictions are performed starting either from the protein structure or, more
      importantly, from the protein sequence. This latter task, to the best of our
      knowledge, is exploited for the first time. The method was trained and tested on
      a data set derived from ProTherm, which is presently the most comprehensive
      available database of thermodynamic experimental data of free energy changes of
      protein stability upon mutation under different conditions. I-Mutant2.0 can be
      used both as a classifier for predicting the sign of the protein stability change
      upon mutation and as a regression estimator for predicting the related
      DeltaDeltaG values. Acting as a classifier, I-Mutant2.0 correctly predicts (with
      a cross-validation procedure) 80% or 77% of the data set, depending on the usage
      of structural or sequence information, respectively. When predicting DeltaDeltaG
      values associated with mutations, the correlation of predicted with
      expected/experimental values is 0.71 (with a standard error of 1.30 kcal/mol) and
      0.62 (with a standard error of 1.45 kcal/mol) when structural or sequence
      information are respectively adopted. Our web interface allows the selection of a
      predictive mode that depends on the availability of the protein structure and/or
      sequence. In this latter case, the web server requires only pasting of a protein
      sequence in a raw format. We therefore introduce I-Mutant2.0 as a unique and
      valuable helper for protein design, even when the protein structure is not yet
      known with atomic resolution. AVAILABILITY:
      http://gpcr.biocomp.unibo.it/cgi/predictors/I-Mutant2.0/I-Mutant2.0.cgi.

PMID- 15980479
TI  - MutDB services: interactive structural analysis of mutation data.
AB  - Non-synonymous single nucleotide polymorphisms (SNPs) and mutations have been
      associated with human phenotypes and disease. As more and more SNPs are mapped to
      phenotypes, understanding how these variations affect the function and expression
      of genes and gene products becomes an important endeavor. We have developed a set
      of tools to aid in the understanding of how amino acid substitutions affect
      protein structures. To do this, we have annotated SNPs in dbSNP and amino acid
      substitutions in Swiss-Prot with protein structural information, if available. We
      then developed a novel web interface to this data that allows for visualization
      of the location of these substitutions. We have also developed a web service
      interface to the dataset and developed interactive plugins for UCSF's Chimera
      structural modeling tool and PyMOL that integrate our annotations with these
      sophisticated structural visualization and modeling tools. The web services
      portal and plugins can be downloaded from http://www.lifescienceweb.org/ and the
      web interface is at http://www.mutdb.org/.

PMID- 15980480
TI  - MAVL/StickWRLD for protein: visualizing protein sequence families to detect non
      consensus features.
AB  - A fundamental problem with applying Consensus, Weight-Matrix or hidden Markov
      models as search tools for biosequences is that there is no way to know, from the
      model, if the modeled sequences display any dependencies between positional
      identities. In some instances, these dependencies are crucial in correctly
      accepting or rejecting other sequences as members of the family. MAVL (multiple
      alignment variation linker) and StickWRLD provide a web-based method to visually
      survey the model-training sequences to discover and characterize possible
      dependencies. Initially introduced for nucleic acid sequences, with
      MAVL/StickWRLD, it is easy to distinguish typical DNA or RNA structural
      dependencies in input families, identify mixed populations of distinct
      subfamilies, or discover novel dependencies that result from binding interactions
      or other selective pressures [W. Ray (2004) Nucleic Acids Res., 32, W59-W63].
      Since the announcement of MAVL/StickWRLD for nucleic acids, one of the most
      requested new features has been the extension of this visualization method to
      support protein alignments. We are pleased to report that this extension has been
      successful, that the basic visualization has been augmented in several ways to
      enhance protein viewing, and that the results with protein alignments are even
      more dramatic than with NA alignments. MAVL/StickWRLD can be accessed at
      http://www.microbial-pathogenesis.org/stickwrld/.

PMID- 15980481
TI  - PPG: online generation of protein pictures and animations.
AB  - The protein picture generator (PPG) is an online service to generate pictures of
      a protein structure. Its design was conceived as an answer to the need expressed
      by a part of the community to have some means to produce simply complex pictures
      to insert in publications or in presentations. PPG can produce static or animated
      pictures. It can be accessed at http://bioserv.rpbs.jussieu.fr/cgi-bin/PPG.

PMID- 15980482
TI  - BIOVERSE: enhancements to the framework for structural, functional and contextual
      modeling of proteins and proteomes.
AB  - We have made a number of enhancements to the previously described Bioverse web
      server and computational biology framework
      (http://bioverse.compbio.washington.edu). In this update, we provide an overview
      of the new features available that include: (i) expansion of the number of
      organisms represented in the Bioverse and addition of new data sources and novel
      prediction techniques not available elsewhere, including network-based
      annotation; (ii) reengineering the database backend and supporting code resulting
      in significant speed, search and ease-of use improvements; and (iii) creation of
      a stateful and dynamic web application frontend to improve interface speed and
      usability. Integrated Java-based applications also allow dynamic visualization of
      real and predicted protein interaction networks.

PMID- 15980483
TI  - Metabolic PathFinding: inferring relevant pathways in biochemical networks.
AB  - Our knowledge of metabolism can be represented as a network comprising several
      thousands of nodes (compounds and reactions). Several groups applied graph theory
      to analyse the topological properties of this network and to infer metabolic
      pathways by path finding. This is, however, not straightforward, with a major
      problem caused by traversing irrelevant shortcuts through highly connected nodes,
      which correspond to pool metabolites and co-factors (e.g. H2O, NADP and H+). In
      this study, we present a web server implementing two simple approaches, which
      circumvent this problem, thereby improving the relevance of the inferred
      pathways. In the simplest approach, the shortest path is computed, while
      filtering out the selection of highly connected compounds. In the second
      approach, the shortest path is computed on the weighted metabolic graph where
      each compound is assigned a weight equal to its connectivity in the network. This
      approach significantly increases the accuracy of the inferred pathways, enabling
      the correct inference of relatively long pathways (e.g. with as many as eight
      intermediate reactions). Available options include the calculation of the k
      shortest paths between two specified seed nodes (either compounds or reactions).
      Multiple requests can be submitted in a queue. Results are returned by email, in
      textual as well as graphical formats (available in
      http://www.scmbb.ulb.ac.be/pathfinding/).

PMID- 15980484
TI  - SiteEngines: recognition and comparison of binding sites and protein-protein
      interfaces.
AB  - Protein surface regions with similar physicochemical properties and shapes may
      perform similar functions and bind similar binding partners. Here we present two
      web servers and software packages for recognition of the similarity of binding
      sites and interfaces. Both methods recognize local geometrical and
      physicochemical similarity, which can be present even in the absence of overall
      sequence or fold similarity. The first method, SiteEngine
      (http:/bioinfo3d.cs.tau.ac.il/SiteEngine), receives as an input two protein
      structures and searches the complete surface of one protein for regions similar
      to the binding site of the other. The second, Interface-to-Interface (I2I)
      SiteEngine (http:/bioinfo3d.cs.tau.ac.il/I2I-SiteEngine), compares protein
      protein interfaces, which are regions of interaction between two protein
      molecules. It receives as an input two structures of protein-protein complexes,
      extracts the interfaces and finds the three-dimensional transformation that
      maximizes the similarity between two pairs of interacting binding sites. The
      output of both servers consists of a superimposition in PDB file format and a
      list of physicochemical properties shared by the compared entities. The methods
      are highly efficient and the freely available software packages are suitable for
      large-scale database searches of the entire PDB.

PMID- 15980485
TI  - POPSCOMP: an automated interaction analysis of biomolecular complexes.
AB  - Large-scale analysis of biomolecular complexes reveals the functional network
      within the cell. Computational methods are required to extract the essential
      information from the available data. The POPSCOMP server is designed to calculate
      the interaction surface between all components of a given complex structure
      consisting of proteins, DNA or RNA molecules. The server returns matrices and
      graphs of surface area burial that can be used to automatically annotate
      components and residues that are involved in complex formation, to pinpoint
      conformational changes and to estimate molecular interaction energies. The
      analysis can be performed on a per-atom level or alternatively on a per-residue
      level for low-resolution structures. Here, we present an analysis of ribosomal
      structures in complex with various antibiotics to exemplify the potential and
      limitations of automated complex analysis. The POPSCOMP server is accessible at
      http://ibivu.cs.vu.nl/programs/popscompwww/.

PMID- 15980486
TI  - EVAcon: a protein contact prediction evaluation service.
AB  - Here we introduce EVAcon, an automated web service that evaluates the performance
      of contact prediction servers. Currently, EVAcon is monitoring nine servers, four
      of which are specialized in contact prediction and five are general structure
      prediction servers. Results are compared for all newly determined experimental
      structures deposited into PDB ( approximately 5-50 per week). EVAcon allows for a
      precise comparison of the results based on a system of common protein subsets and
      the commonly accepted evaluation criteria that are also used in the corresponding
      category of the CASP assessment. EVAcon is a new service added to the
      functionality of the EVA system for the continuous evaluation of protein
      structure prediction servers. The new service is accesible from any of the three
      EVA mirrors: PDG (CNB-CSIC, Madrid)
      (http://www.pdg.cnb.uam.es/eva/con/index.html); CUBIC (Columbia University, NYC)
      (http://cubic.bioc.columbia.edu/eva/con/index.html); and Sali Lab (UCSF, San
      Francisco) (http://eva.compbio.ucsf.edu/~eva/con/index.html).

PMID- 15980487
TI  - VisANT: data-integrating visual framework for biological networks and modules.
AB  - VisANT is a web-based software framework for visualizing and analyzing many types
      of networks of biological interactions and associations. Networks are a useful
      computational tool for representing many types of biological data, such as
      biomolecular interactions, cellular pathways and functional modules. Given user
      defined sets of interactions or groupings between genes or proteins, VisANT
      provides: (i) a visual interface for combining and annotating network data, (ii)
      supporting function and annotation data for different genomes from the Gene
      Ontology and KEGG databases and (iii) the statistical and analytical tools needed
      for extracting topological properties of the user-defined networks. Users can
      customize, modify, save and share network views with other users, and import
      basic network data representations from their own data sources, and from standard
      exchange formats such as PSI-MI and BioPAX. The software framework we employ also
      supports the development of more sophisticated visualization and analysis
      functions through its open API for Java-based plug-ins. VisANT is distributed
      freely via the web at http://visant.bu.edu and can also be downloaded for
      individual use.

PMID- 15980488
TI  - MovieMaker: a web server for rapid rendering of protein motions and interactions.
AB  - MovieMaker is a web server that allows short ( approximately 10 s), downloadable
      movies of protein motions to be generated. It accepts PDB files or PDB accession
      numbers as input and automatically calculates, renders and merges the necessary
      image files to create colourful animations covering a wide range of protein
      motions and other dynamic processes. Users have the option of animating (i)
      simple rotation, (ii) morphing between two end-state conformers, (iii) short
      scale, picosecond vibrations, (iv) ligand docking, (v) protein oligomerization,
      (vi) mid-scale nanosecond (ensemble) motions and (vii) protein folding/unfolding.
      MovieMaker does not perform molecular dynamics calculations. Instead it is an
      animation tool that uses a sophisticated superpositioning algorithm in
      conjunction with Cartesian coordinate interpolation to rapidly and automatically
      calculate the intermediate structures needed for many of its animations. Users
      have extensive control over the rendering style, structure colour, animation
      quality, background and other image features. MovieMaker is intended to be a
      general-purpose server that allows both experts and non-experts to easily
      generate useful, informative protein animations for educational and illustrative
      purposes. MovieMaker is accessible at
      http://wishart.biology.ualberta.ca/moviemaker.

PMID- 15980489
TI  - Protein structure prediction servers at University College London.
AB  - A number of state-of-the-art protein structure prediction servers have been
      developed by researchers working in the Bioinformatics Unit at University College
      London. The popular PSIPRED server allows users to perform secondary structure
      prediction, transmembrane topology prediction and protein fold recognition. More
      recent servers include DISOPRED for the prediction of protein dynamic disorder
      and DomPred for domain boundary prediction. These servers are available from our
      software home page at http://bioinf.cs.ucl.ac.uk/software.html.

PMID- 15980490
TI  - PatchDock and SymmDock: servers for rigid and symmetric docking.
AB  - Here, we describe two freely available web servers for molecular docking. The
      PatchDock method performs structure prediction of protein-protein and protein
      small molecule complexes. The SymmDock method predicts the structure of a
      homomultimer with cyclic symmetry given the structure of the monomeric unit. The
      inputs to the servers are either protein PDB codes or uploaded protein
      structures. The services are available at http://bioinfo3d.cs.tau.ac.il. The
      methods behind the servers are very efficient, allowing large-scale docking
      experiments.

PMID- 15980491
TI  - H++: a server for estimating pKas and adding missing hydrogens to macromolecules.
AB  - The structure and function of macromolecules depend critically on the ionization
      (protonation) states of their acidic and basic groups. A number of existing
      practical methods predict protonation equilibrium pK constants of macromolecules
      based upon their atomic resolution Protein Data Bank (PDB) structures; the
      calculations are often performed within the framework of the continuum
      electrostatics model. Unfortunately, these methodologies are complex, involve
      multiple steps and require considerable investment of effort. Our web server
      http://biophysics.cs.vt.edu/H++ provides access to a tool that automates this
      process, allowing both experts and novices to quickly obtain estimates of pKs as
      well as other related characteristics of biomolecules such as isoelectric points,
      titration curves and energies of protonation microstates. Protons are added to
      the input structure according to the calculated ionization states of its
      titratable groups at the user-specified pH; the output is in the PQR (PDB +
      charges + radii) format. In addition, corresponding coordinate and topology files
      are generated in the format supported by the molecular modeling package AMBER.
      The server is intended for a broad community of biochemists, molecular modelers,
      structural biologists and drug designers; it can also be used as an educational
      tool in biochemistry courses.

PMID- 15980492
TI  - PCE: web tools to compute protein continuum electrostatics.
AB  - PCE (protein continuum electrostatics) is an online service for protein
      electrostatic computations presently based on the MEAD (macroscopic
      electrostatics with atomic detail) package initially developed by D. Bashford
      [(2004) Front Biosci., 9, 1082-1099]. This computer method uses a macroscopic
      electrostatic model for the calculation of protein electrostatic properties, such
      as pK(a) values of titratable groups and electrostatic potentials. The MEAD
      package generates electrostatic energies via finite difference solution to the
      Poisson-Boltzmann equation. Users submit a PDB file and PCE returns potentials
      and pK(a) values as well as color (static or animated) figures displaying
      electrostatic potentials mapped on the molecular surface. This service is
      intended to facilitate electrostatics analyses of proteins and thereby broaden
      the accessibility to continuum electrostatics to the biological community. PCE
      can be accessed at http://bioserv.rpbs.jussieu.fr/PCE.

PMID- 15980493
TI  - DeNovoID: a web-based tool for identifying peptides from sequence and mass tags
      deduced from de novo peptide sequencing by mass spectroscopy.
AB  - One of the core activities of high-throughput proteomics is the identification of
      peptides from mass spectra. Some peptides can be identified using spectral
      matching programs like Sequest or Mascot, but many spectra do not produce high
      quality database matches. De novo peptide sequencing is an approach to determine
      partial peptide sequences for some of the unidentified spectra. A drawback of de
      novo peptide sequencing is that it produces a series of ordered and disordered
      sequence tags and mass tags rather than a complete, non-degenerate peptide amino
      acid sequence. This incomplete data is difficult to use in conventional search
      programs such as BLAST or FASTA. DeNovoID is a program that has been specifically
      designed to use degenerate amino acid sequence and mass data derived from MS
      experiments to search a peptide database. Since the algorithm employed depends on
      the amino acid composition of the peptide and not its sequence, DeNovoID does not
      have to consider all possible sequences, but rather a smaller number of
      compositions consistent with a spectrum. DeNovoID also uses a geometric indexing
      scheme that reduces the number of calculations required to determine the best
      peptide match in the database. DeNovoID is available at
      http://proteomics.mcw.edu/denovoid.

PMID- 15980494
TI  - The FoldX web server: an online force field.
AB  - FoldX is an empirical force field that was developed for the rapid evaluation of
      the effect of mutations on the stability, folding and dynamics of proteins and
      nucleic acids. The core functionality of FoldX, namely the calculation of the
      free energy of a macromolecule based on its high-resolution 3D structure, is now
      publicly available through a web server at http://foldx.embl.de/. The current
      release allows the calculation of the stability of a protein, calculation of the
      positions of the protons and the prediction of water bridges, prediction of metal
      binding sites and the analysis of the free energy of complex formation. Alanine
      scanning, the systematic truncation of side chains to alanine, is also included.
      In addition, some reporting functions have been added, and it is now possible to
      print both the atomic interaction networks that constitute the protein, print the
      structural and energetic details of the interactions per atom or per residue, as
      well as generate a general quality report of the pdb structure. This core
      functionality will be further extended as more FoldX applications are developed.

PMID- 15980495
TI  - enoLOGOS: a versatile web tool for energy normalized sequence logos.
AB  - enoLOGOS is a web-based tool that generates sequence logos from various input
      sources. Sequence logos have become a popular way to graphically represent DNA
      and amino acid sequence patterns from a set of aligned sequences. Each position
      of the alignment is represented by a column of stacked symbols with its total
      height reflecting the information content in this position. Currently, the
      available web servers are able to create logo images from a set of aligned
      sequences, but none of them generates weighted sequence logos directly from
      energy measurements or other sources. With the advent of high-throughput
      technologies for estimating the contact energy of different DNA sequences, tools
      that can create logos directly from binding affinity data are useful to
      researchers. enoLOGOS generates sequence logos from a variety of input data,
      including energy measurements, probability matrices, alignment matrices, count
      matrices and aligned sequences. Furthermore, enoLOGOS can represent the mutual
      information of different positions of the consensus sequence, a unique feature of
      this tool. Another web interface for our software, C2H2-enoLOGOS, generates logos
      for the DNA-binding preferences of the C2H2 zinc-finger transcription factor
      family members. enoLOGOS and C2H2-enoLOGOS are accessible over the web at
      http://biodev.hgen.pitt.edu/enologos/.

PMID- 15980496
TI  - SPACE: a suite of tools for protein structure prediction and analysis based on
      complementarity and environment.
AB  - We describe a suite of SPACE tools for analysis and prediction of structures of
      biomolecules and their complexes. LPC/CSU software provides a common definition
      of inter-atomic contacts and complementarity of contacting surfaces to analyze
      protein structure and complexes. In the current version of LPC/CSU, analyses of
      water molecules and nucleic acids have been added, together with improved and
      expanded visualization options using Chime or Java based Jmol. The SPACE suite
      includes servers and programs for: structural analysis of point mutations
      (MutaProt); side chain modeling based on surface complementarity (SCCOMP);
      building a crystal environment and analysis of crystal contacts (CryCo);
      construction and analysis of protein contact maps (CMA) and molecular docking
      software (LIGIN). The SPACE suite is accessed at
      http://ligin.weizmann.ac.il/space.

PMID- 15980497
TI  - TOUCAN 2: the all-inclusive open source workbench for regulatory sequence
      analysis.
AB  - We present the second and improved release of the TOUCAN workbench for cis
      regulatory sequence analysis. TOUCAN implements and integrates fast state-of-the
      art methods and strategies in gene regulation bioinformatics, including
      algorithms for comparative genomics and for the detection of cis-regulatory
      modules. This second release of TOUCAN has become open source and thereby carries
      the potential to evolve rapidly. The main goal of TOUCAN is to allow a user to
      come to testable hypotheses regarding the regulation of a gene or of a set of co
      regulated genes. TOUCAN can be launched from this location:
      http://www.esat.kuleuven.ac.be/~saerts/software/toucan.php.

PMID- 15980498
TI  - AthaMap web tools for database-assisted identification of combinatorial cis
      regulatory elements and the display of highly conserved transcription factor
      binding sites in Arabidopsis thaliana.
AB  - The AthaMap database generates a map of cis-regulatory elements for the
      Arabidopsis thaliana genome. AthaMap contains more than 7.4 x 10(6) putative
      binding sites for 36 transcription factors (TFs) from 16 different TF families. A
      newly implemented functionality allows the display of subsets of higher conserved
      transcription factor binding sites (TFBSs). Furthermore, a web tool was developed
      that permits a user-defined search for co-localizing cis-regulatory elements. The
      user can specify individually the level of conservation for each TFBS and a
      spacer range between them. This web tool was employed for the identification of
      co-localizing sites of known interacting TFs and TFs containing two DNA-binding
      domains. More than 1.8 x 10(5) combinatorial elements were annotated in the
      AthaMap database. These elements can also be used to identify more complex co
      localizing elements consisting of up to four TFBSs. The AthaMap database and the
      connected web tools are a valuable resource for the analysis and the prediction
      of gene expression regulation at http://www.athamap.de.

PMID- 15980499
TI  - Identifying synonymous regulatory elements in vertebrate genomes.
AB  - Synonymous gene regulation, defined by regulatory elements driving shared
      temporal and/or spatial aspects of gene expression, is most probably predicated
      on genomic elements that contain similar modules of certain transcription factor
      binding sites (TFBS). We have developed a method to scan vertebrate genomes for
      evolutionary conserved modules of TFBS in a predefined configuration, and created
      a tool, named SynoR that identifies synonymous regulatory elements (SREs) in
      vertebrate genomes. SynoR performs de novo identification of SREs utilizing known
      patterns of TFBS in active regulatory elements (REs) as seeds for genome scans.
      Layers of multiple-species conservation allow the use of differential
      phylogenetic sequence conservation filters in search of SREs and the results are
      displayed such as to provide an extensive annotation of the genes containing the
      detected REs. Gene Ontology categories are utilized to further functionally
      classify the identified genes, and integrated GNF Expression Atlas 2 data allow
      the cataloging of tissue-specificities of the predicted SREs. SynoR is publicly
      available at http://synor.dcode.org.

PMID- 15980500
TI  - CisMols Analyzer: identification of compositionally similar cis-element clusters
      in ortholog conserved regions of coordinately expressed genes.
AB  - Combinatorial interactions of sequence-specific trans-acting factors with
      localized genomic cis-element clusters are the principal mechanism for regulating
      tissue-specific and developmental gene expression. With the emergence of
      expanding numbers of genome-wide expression analyses, the identification of the
      cis-elements responsible for specific patterns of transcriptional regulation
      represents a critical area of investigation. Computational methods for the
      identification of functional cis-regulatory modules are difficult to devise,
      principally because of the short length and degenerate nature of individual cis
      element binding sites and the inherent complexity that is generated by
      combinatorial interactions within cis-clusters. Filtering candidate cis-element
      clusters based on phylogenetic conservation is helpful for an individual ortholog
      gene pair, but combining data from cis-conservation and coordinate expression
      across multiple genes is a more difficult problem. To approach this, we have
      extended an ortholog gene-pair database with additional analytical architecture
      to allow for the analysis and identification of maximal numbers of
      compositionally similar and phylogenetically conserved cis-regulatory element
      clusters from a list of user-selected genes. The system has been successfully
      tested with a series of functionally related and microarray profile-based co
      expressed ortholog pairs of promoters and genes using known regulatory regions as
      training sets and co-expressed genes in the olfactory and immunohematologic
      systems as test sets. CisMols Analyzer is accessible via a Web interface at
      http://cismols.cchmc.org/.

PMID- 15980501
TI  - WordSpy: identifying transcription factor binding motifs by building a dictionary
      and learning a grammar.
AB  - Transcription factor (TF) binding sites or motifs (TFBMs) are functional cis
      regulatory DNA sequences that play an essential role in gene transcriptional
      regulation. Although many experimental and computational methods have been
      developed, finding TFBMs remains a challenging problem. We propose and develop a
      novel dictionary based motif finding algorithm, which we call WordSpy. One
      significant feature of WordSpy is the combination of a word counting method and a
      statistical model which consists of a dictionary of motifs and a grammar
      specifying their usage. The algorithm is suitable for genome-wide motif finding;
      it is capable of discovering hundreds of motifs from a large set of promoters in
      a single run. We further enhance WordSpy by applying gene expression information
      to separate true TFBMs from spurious ones, and by incorporating negative
      sequences to identify discriminative motifs. In addition, we also use randomly
      selected promoters from the genome to evaluate the significance of the discovered
      motifs. The output from WordSpy consists of an ordered list of putative motifs
      and a set of regulatory sequences with motif binding sites highlighted. The web
      server of WordSpy is available at http://cic.cs.wustl.edu/wordspy.

PMID- 15980502
TI  - ARGO: a web system for the detection of degenerate motifs and large-scale
      recognition of eukaryotic promoters.
AB  - Reliable recognition of the promoters in eukaryotic genomes remains an open
      issue. This is largely owing to the poor understanding of the features of the
      structural-functional organization of the eukaryotic promoters essential for
      their function and recognition. However, it was demonstrated that detection of
      ensembles of regulatory signals characteristic of specific promoter groups
      increases the accuracy of promoter recognition and prediction of specific
      expression features of the queried genes. The ARGO_Motifs package was developed
      for the detection of sets of region-specific degenerate oligonucleotide motifs in
      the regulatory regions of the eukaryotic genes. The ARGO_Viewer package was
      developed for the recognition of tissue-specific gene promoters based on the
      presence and distribution of oligonucleotide motifs obtained by the ARGO_Motifs
      program. Analysis and recognition of tissue-specific promoters in five gene
      samples demonstrated high quality of promoter recognition. The public version of
      the ARGO system is available at http://wwwmgs2.bionet.nsc.ru/argo/ and http://emj
      pc.ics.uci.edu/argo/.

PMID- 15980503
TI  - PromoterPlot: a graphical display of promoter similarities by pattern
      recognition.
AB  - PromoterPlot (http://promoterplot.fmi.ch) is a web-based tool for simplifying the
      display and processing of transcription factor searches using either the
      commercial or free TransFac distributions. The input sequence is a TransFac
      search (public version) or FASTA/Affymetrix IDs (local install). It uses an
      intuitive pattern recognition algorithm for finding similarities between groups
      of promoters by dividing transcription factor predictions into conserved triplet
      models. To minimize the number of false-positive models, it can optionally
      exclude factors that are known to be unexpressed or inactive in the cells being
      studied based on microarray or proteomic expression data. The program will also
      estimate the likelihood of finding a pattern by chance based on the frequency
      observed in a control set of mammalian promoters we obtained from Genomatix. The
      results are stored as an interactive SVG web page on our server.

PMID- 15980504
TI  - POCO: discovery of regulatory patterns from promoters of oppositely expressed
      gene sets.
AB  - Functionally associated genes tend to be co-expressed, which indicates that they
      could also be co-regulated. Since co-regulation is usually governed by
      transcription factors via their specific binding elements, putative regulators
      can be identified from promoter sets of (co-expressed) genes by screening for
      over-represented nucleotide patterns. Here, we present a program, POCO, which
      discovers such over-represented patterns from either one or two promoter sets.
      Typical microarray experiments yield up- and down-regulated gene sets that may
      represent, for example, distinct defense pathways. Assuming that a functional
      transcription factor cannot simultaneously both up- and down-regulate the gene
      sets, its binding element should respectively be over- and under-represented in
      the corresponding promoter sets. This idea is implemented in POCO, which tests
      the hypothesis that the distributions of a pattern differ among three sets of
      promoters: up-regulated, down-regulated and randomly-chosen. In the program,
      pattern discovery is based on explicit enumeration of all possible patterns on
      the alphabet (A, C, G, T and N). The mean occurrences and SDs of the patterns are
      estimated using bootstrapping and their significance is assessed using ANOVA F
      statistics, Tukey's honestly significantly difference test and P-values. The
      program is freely available at http://ekhidna.biocenter.helsinki.fi/poco.

PMID- 15980505
TI  - P-Match: transcription factor binding site search by combining patterns and
      weight matrices.
AB  - P-Match is a new tool for identifying transcription factor (TF) binding sites in
      DNA sequences. It combines pattern matching and weight matrix approaches thus
      providing higher accuracy of recognition than each of the methods alone. P-Match
      is closely interconnected with the TRANSFAC database. In particular, P-Match uses
      the matrix library as well as sets of aligned known TF-binding sites collected in
      TRANSFAC and therefore provides the possibility to search for a large variety of
      different TF binding sites. Using results of extensive tests of recognition
      accuracy, we selected three sets of optimized cut-off values that minimize either
      false negatives or false positives, or the sum of both errors. Comparison with
      the weight matrix approaches such as Matchtrade mark tool shows that P-Match
      generally provides superior recognition accuracy in the area of low false
      negative errors (high sensitivity). As familiar to the user of Matchtrade mark, P
      Match also allows to save user-specific profiles that include selected subsets of
      matrices with corresponding TF-binding sites or user-defined cut-off values.
      Furthermore, a number of tissue-specific profiles are provided that were compiled
      by the TRANSFAC team. A public version of the P-Match tool is available at
      http://www.gene-regulation.com/cgi-bin/pub/programs/pmatch/bin/p-match.cgi.

PMID- 15980506
TI  - T-Reg Comparator: an analysis tool for the comparison of position weight
      matrices.
AB  - T-Reg Comparator is a novel software tool designed to support research into
      transcriptional regulation. Sequence motifs representing transcription factor
      binding sites are usually encoded as position weight matrices. The user inputs a
      set of such weight matrices or binding site sequences and our program matches
      them against the T-Reg database, which is presently built on data from the
      Transfac [E. Wingender (2004) In Silico Biol., 4, 55-61] and Jaspar [A. Sandelin,
      W. Alkema, P. Engstrom, W. W. Wasserman and B. Lenhard (2004) Nucleic Acids Res.,
      32, D91-D94]. Our tool delivers a detailed report on similarities between user
      supplied motifs and motifs in the database. Apart from simple one-to-one
      relationships, T-Reg Comparator is also able to detect similarities between
      submatrices. In addition, we provide a user interface to a program for sequence
      scanning with weight matrices. Typical areas of application for T-Reg Comparator
      are motif and regulatory module finding and annotation of regulatory genomic
      regions. T-Reg Comparator is available at http://treg.molgen.mpg.de.

PMID- 15980507
TI  - RPBS: a web resource for structural bioinformatics.
AB  - RPBS (Ressource Parisienne en Bioinformatique Structurale) is a resource
      dedicated primarily to structural bioinformatics. It is the result of a joint
      effort by several teams to set up an interface that offers original and powerful
      methods in the field. As an illustration, we focus here on three such methods
      uniquely available at RPBS: AUTOMAT for sequence databank scanning, YAKUSA for
      structure databank scanning and WLOOP for homology loop modelling. The RPBS
      server can be accessed at http://bioserv.rpbs.jussieu.fr/ and the specific
      services at http://bioserv.rpbs.jussieu.fr/SpecificServices.html.

PMID- 15980508
TI  - FOOTER: a web tool for finding mammalian DNA regulatory regions using
      phylogenetic footprinting.
AB  - FOOTER is a newly developed algorithm that analyzes homologous mammalian promoter
      sequences in order to identify transcriptional DNA regulatory 'signals'. FOOTER
      uses prior knowledge about the binding site preferences of the transcription
      factors (TFs) in the form of position-specific scoring matrices (PSSMs). The PSSM
      models are generated from known mammalian binding sites from the TRANSFAC
      database. In a test set of 72 confirmed binding sites (most of them not present
      in TRANSFAC) of 19 TFs, it exhibited 83% sensitivity and 72% specificity. FOOTER
      is accessible over the web at http://biodev.hgen.pitt.edu/Footer/.

PMID- 15980509
TI  - CONREAL web server: identification and visualization of conserved transcription
      factor binding sites.
AB  - The use of orthologous sequences and phylogenetic footprinting approaches have
      become popular for the recognition of conserved and potentially functional
      sequences. Several algorithms have been developed for the identification of
      conserved transcription factor binding sites (TFBSs), which are characterized by
      their relatively short and degenerative recognition sequences. The CONREAL
      (conserved regulatory elements anchored alignment) web server provides a
      versatile interface to CONREAL-, LAGAN-, BLASTZ- and AVID-based predictions of
      conserved TFBSs in orthologous promoters. Comparative analysis using different
      algorithms can be started by keyword without any prior sequence retrieval. The
      interface is available at http://conreal.niob.knaw.nl.

PMID- 15980510
TI  - GeneMark: web software for gene finding in prokaryotes, eukaryotes and viruses.
AB  - The task of gene identification frequently confronting researchers working with
      both novel and well studied genomes can be conveniently and reliably solved with
      the help of the GeneMark web software (http://opal.biology.gatech.edu/GeneMark/).
      The website provides interfaces to the GeneMark family of programs designed and
      tuned for gene prediction in prokaryotic, eukaryotic and viral genomic sequences.
      Currently, the server allows the analysis of nearly 200 prokaryotic and >10
      eukaryotic genomes using species-specific versions of the software and pre
      computed gene models. In addition, genes in prokaryotic sequences from novel
      genomes can be identified using models derived on the spot upon sequence
      submission, either by a relatively simple heuristic approach or by the full
      fledged self-training program GeneMarkS. A database of reannotations of >1000
      viral genomes by the GeneMarkS program is also available from the web site. The
      GeneMark website is frequently updated to provide the latest versions of the
      software and gene models.

PMID- 15980511
TI  - BASys: a web server for automated bacterial genome annotation.
AB  - BASys (Bacterial Annotation System) is a web server that supports automated, in
      depth annotation of bacterial genomic (chromosomal and plasmid) sequences. It
      accepts raw DNA sequence data and an optional list of gene identification
      information and provides extensive textual annotation and hyperlinked image
      output. BASys uses >30 programs to determine approximately 60 annotation
      subfields for each gene, including gene/protein name, GO function, COG function,
      possible paralogues and orthologues, molecular weight, isoelectric point, operon
      structure, subcellular localization, signal peptides, transmembrane regions,
      secondary structure, 3D structure, reactions and pathways. The depth and detail
      of a BASys annotation matches or exceeds that found in a standard SwissProt
      entry. BASys also generates colorful, clickable and fully zoomable maps of each
      query chromosome to permit rapid navigation and detailed visual analysis of all
      resulting gene annotations. The textual annotations and images that are provided
      by BASys can be generated in approximately 24 h for an average bacterial
      chromosome (5 Mb). BASys annotations may be viewed and downloaded anonymously or
      through a password protected access system. The BASys server and databases can
      also be downloaded and run locally. BASys is accessible at
      http://wishart.biology.ualberta.ca/basys.

PMID- 15980512
TI  - BABELOMICS: a suite of web tools for functional annotation and analysis of groups
      of genes in high-throughput experiments.
AB  - We present Babelomics, a complete suite of web tools for the functional analysis
      of groups of genes in high-throughput experiments, which includes the use of
      information on Gene Ontology terms, interpro motifs, KEGG pathways, Swiss-Prot
      keywords, analysis of predicted transcription factor binding sites, chromosomal
      positions and presence in tissues with determined histological characteristics,
      through five integrated modules: FatiGO (fast assignment and transference of
      information), FatiWise, transcription factor association test, GenomeGO and
      tissues mining tool, respectively. Additionally, another module, FatiScan,
      provides a new procedure that integrates biological information in combination
      with experimental results in order to find groups of genes with modest but
      coordinate significant differential behaviour. FatiScan is highly sensitive and
      is capable of finding significant asymmetries in the distribution of genes of
      common function across a list of ordered genes even if these asymmetries were not
      extreme. The strong multiple-testing nature of the contrasts made by the tools is
      taken into account. All the tools are integrated in the gene expression analysis
      package GEPAS. Babelomics is the natural evolution of our tool FatiGO (which
      analysed almost 22,000 experiments during the last year) to include more sources
      on information and new modes of using it. Babelomics can be found at
      http://www.babelomics.org.

PMID- 15980513
TI  - AUGUSTUS: a web server for gene prediction in eukaryotes that allows user-defined
      constraints.
AB  - We present a WWW server for AUGUSTUS, a software for gene prediction in
      eukaryotic genomic sequences that is based on a generalized hidden Markov model,
      a probabilistic model of a sequence and its gene structure. The web server allows
      the user to impose constraints on the predicted gene structure. A constraint can
      specify the position of a splice site, a translation initiation site or a stop
      codon. Furthermore, it is possible to specify the position of known exons and
      intervals that are known to be exonic or intronic sequence. The number of
      constraints is arbitrary and constraints can be combined in order to pin down
      larger parts of the predicted gene structure. The result then is the most likely
      gene structure that complies with all given user constraints, if such a gene
      structure exists. The specification of constraints is useful when part of the
      gene structure is known, e.g. by expressed sequence tag or protein sequence
      alignments, or if the user wants to change the default prediction. The web
      interface and the downloadable stand-alone program are available free of charge
      at http://augustus.gobics.de/submission.

PMID- 15980514
TI  - Integrating protein annotation resources through the Distributed Annotation
      System.
AB  - Using the Distributed Annotation System (DAS) we have created a protein
      annotation resource available at our web page: http://www.cbs.dtu.dk, as a part
      of the BioSapiens Network of Excellence EU FP6 project. The DAS protocol allows
      us to gather layers of annotation data for a given sequence and thereby gain an
      overview of the sequence's features. A user-friendly graphical client has also
      been developed (http://www.cbs.dtu.dk/cgi-bin/das), which demonstrates the
      possibility of integrating DAS annotation data from multiple sources into a
      simple graphical view. The client displays protein feature annotations from the
      Center for Biological Sequence Analysis as well as from the BioSapiens reference
      UniProt server (http://www.ebi.ac.uk/das-srv/uniprot/das) at the European
      Bioinformatics Institute. Other DAS data sources for protein annotation will be
      added as they become available.

PMID- 15980515
TI  - MICheck: a web tool for fast checking of syntactic annotations of bacterial
      genomes.
AB  - The annotation of newly sequenced bacterial genomes begins with running several
      automatic analysis methods, with major emphasis on the identification of protein
      coding genes. DNA sequences are heterogeneous in local nucleotide composition and
      this leads sometimes to sequences being annotated as authentic genes when they
      are not protein-coding genes or are true but uncharacterized protein-coding
      genes. This first annotation step is generally followed by an expert manual
      annotation of the predicted genes. The genomic data (sequence and annotations)
      organized in an appropriate databank file format is subsequently submitted to an
      entry point of the International Nucleotide Sequence Database. These procedures
      are inevitably subject to mistakes, and this can lead to unintentional syntactic
      annotation errors being stored in public databanks. Here, we present a new web
      program, MICheck (MIcrobial genome Checker), that enables rapid verification of
      sets of annotated genes and frameshifts in previously published bacterial
      genomes. The web interface allows one easily to investigate the MICheck results,
      i.e. inaccurate or missed gene annotations: a graphical representation is drawn,
      in which the genomic context of a unique coding DNA sequence annotation or a
      predicted frameshift is given, using information on the coding potential (curves)
      and annotation of the neighbouring genes. We illustrate some capabilities of the
      MICheck site through the analysis of 20 bacterial genomes, 9 of which were
      selected for their 'Reviewed' status in the National Center for Biotechnology
      Information (NCBI) Reference Sequence Project (RefSeq). In the context of the
      numerous re-annotation projects for microbial genomes, this tool can be seen as a
      preliminary step before the functional re-annotation step to check quickly for
      missing or wrongly annotated genes. The MICheck website is accessible at the
      following address: http://www.genoscope.cns.fr/agc/tools/micheck.

PMID- 15980516
TI  - nsSNPAnalyzer: identifying disease-associated nonsynonymous single nucleotide
      polymorphisms.
AB  - Nonsynonymous single nucleotide polymorphisms (nsSNPs) are prevalent in genomes
      and are closely associated with inherited diseases. To facilitate identifying
      disease-associated nsSNPs from a large number of neutral nsSNPs, it is important
      to develop computational tools to predict the nsSNP's phenotypic effect (disease
      associated versus neutral). nsSNPAnalyzer, a web-based software developed for
      this purpose, extracts structural and evolutionary information from a query nsSNP
      and uses a machine learning method called Random Forest to predict the nsSNP's
      phenotypic effect. nsSNPAnalyzer server is available at
      http://snpanalyzer.utmem.edu/.

PMID- 15980517
TI  - SNPAnalyzer: a web-based integrated workbench for single-nucleotide polymorphism
      analysis.
AB  - SNPAnalyzer is a software that performs four essential statistical analyses of
      SNPs in a common computational environment. It is composed of three main modules:
      (i) data manipulation, (ii) analysis and (iii) visualization. The data
      manipulation module is responsible for data input and output, and handles
      genotype, phenotype and genetic distance data. To ensure user convenience, the
      data format is simple. The analysis module performs statistical calculations and
      consists of four subcomponents: (i) Hardy-Weinberg equilibrium, (ii) Haplotype
      Estimation, (iii) linkage disequilibrium (LD) and (iv) quantitative trait locus
      analysis. The main feature of the analysis module is multiple implementations of
      different algorithms and indices for haplotype estimation and for LD analysis.
      This enables users to compare separate results generated by different algorithms,
      which help to avoid biased results acquired by applying a single statistical
      algorithm. The performance of all implemented algorithms has been validated using
      experimentally proven datasets. The visualization module presents most of the
      analyzed results as figures, rather than as simple text, which aids in the
      intuitive understanding of complex data. The SNPAnalyzer has been developed using
      C and C++ and is available at http://www.istech.info/istech/board/login_form.jsp.

PMID- 15980518
TI  - SNP Cutter: a comprehensive tool for SNP PCR-RFLP assay design.
AB  - The Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      is a relatively simple and inexpensive method for genotyping single nucleotide
      polymorphisms (SNPs). It requires minimal investment in instrumentation. Here, we
      describe a web application, 'SNP Cutter,' which designs PCR-RFLP assays on a
      batch of SNPs from the human genome. NCBI dbSNP rs IDs or formatted SNPs are
      submitted into the SNP Cutter which then uses restriction enzymes from a pre
      selected list to perform enzyme selection. The program is capable of designing
      primers for either natural PCR-RFLP or mismatch PCR-RFLP, depending on the SNP
      sequence data. SNP Cutter generates the information needed to evaluate and
      perform genotyping experiments, including a PCR primers list, sizes of original
      amplicons and different allelic fragment after enzyme digestion. Some output data
      is tab-delimited, therefore suitable for database archiving. The SNP Cut-ter is
      available at http://bioinfo.bsd.uchicago.edu/SNP_cutter.htm.

PMID- 15980519
TI  - SNPServer: a real-time SNP discovery tool.
AB  - SNPServer is a real-time flexible tool for the discovery of SNPs (single
      nucleotide polymorphisms) within DNA sequence data. The program uses BLAST, to
      identify related sequences, and CAP3, to cluster and align these sequences. The
      alignments are parsed to the SNP discovery software autoSNP, a program that
      detects SNPs and insertion/deletion polymorphisms (indels). Alternatively, lists
      of related sequences or pre-assembled sequences may be entered for SNP discovery.
      SNPServer and autoSNP use redundancy to differentiate between candidate SNPs and
      sequence errors. For each candidate SNP, two measures of confidence are
      calculated, the redundancy of the polymorphism at a SNP locus and the co
      segregation of the candidate SNP with other SNPs in the alignment. SNPServer is
      available at http://hornbill.cspp.latrobe.edu.au/snpdiscovery.html.

PMID- 15980520
TI  - ARTS: a web-based tool for the set-up of high-throughput genome-wide mapping
      panels for the SNP genotyping of mouse mutants.
AB  - Genome-wide mapping in the identification of novel candidate genes has always
      been the standard method in genetics and genomics to correlate a clinically
      interesting phenotypic trait with a genotype. However, the performance of a
      mapping experiment using classical microsatellite approaches can be very time
      consuming. The high-throughput analysis of single-nucleotide polymorphisms (SNPs)
      has the potential of being the successor of microsatellite analysis routinely
      used for these mapping approaches, where one of the major obstacles is the design
      of the appropriate SNP marker set itself. Here we report on ARTS, an advanced
      retrieval tool for SNPs, which allows researchers to comb freely the public mouse
      dbSNP database for multiple reference and test strains. Several filters can be
      applied in order to improve the sensitivity and the specificity of the search
      results. By employing the panel generator function of this program, it is
      possible to abbreviate the extraction of reliable sequence data for a large
      marker panel including several different mouse strains from days to minutes. The
      concept of ARTS is easily adaptable to other species for which SNP databases are
      available, making it a versatile tool for the use of SNPs as markers for
      genotyping. The web interface is accessible at http://andromeda.gsf.de/arts.

PMID- 15980521
TI  - CAMPO, SCR_FIND and CHC_FIND: a suite of web tools for computational structural
      biology.
AB  - The identification of evolutionarily conserved features of protein structures can
      provide insights into their functional and structural properties. Three methods
      have been developed and implemented as WWW tools, CAMPO, SCR_FIND and CHC_FIND,
      to analyze evolutionarily conserved residues (ECRs), structurally conserved
      regions (SCRs) and conserved hydrophobic contacts (CHCs) in protein families and
      superfamilies, on the basis of their 3D structures and the homologous sequences
      available. The programs identify protein segments that conserve a similar main
      chain conformation, compute residue-to-residue hydrophobic contacts involving
      only apolar atoms common to all the 3D structures analyzed and allow the
      identification of conserved amino-acid sites among protein structures and their
      homologous sequences. The programs also allow the visualization of SCRs, CHCs and
      ECRs directly on the superposed structures and their multiple structural and
      sequence alignments. Tools and tutorials explaining their usage are available at
      http://schubert.bio.uniroma1.it/SCR_FIND,
      http://schubert.bio.uniroma1.it/CHC_FIND and
      http://schubert.bio.uniroma1.it/CAMPO.

PMID- 15980522
TI  - PupasView: a visual tool for selecting suitable SNPs, with putative pathological
      effect in genes, for genotyping purposes.
AB  - We have developed a web tool, PupasView, for the selection of single nucleotide
      polymorphisms (SNPs) with potential phenotypic effect. PupasView constitutes an
      interactive environment in which functional information and population frequency
      data can be used as sequential filters over linkage disequilibrium parameters to
      obtain a final list of SNPs optimal for genotyping purposes. PupasView is the
      first resource that integrates phenotypic effects caused by SNPs at both the
      translational and the transcriptional level. PupasView retrieves SNPs that could
      affect conserved regions that the cellular machinery uses for the correct
      processing of genes (intron/exon boundaries or exonic splicing enhancers),
      predicted transcription factor binding sites and changes in amino acids in the
      proteins for which a putative pathological effect is calculated. The program uses
      the mapping of SNPs in the genome provided by Ensembl. PupasView will be of much
      help in studies of multifactorial disorders, where the use of functional SNPs
      will increase the sensitivity of the identification of the genes responsible for
      the disease. The PupasView web interface is accessible through
      http://pupasview.ochoa.fib.es and through http://www.pupasnp.org.

PMID- 15980523
TI  - AMOD: a morpholino oligonucleotide selection tool.
AB  - AMOD is a web-based program that aids in the functional evaluation of nucleotide
      sequences through sequence characterization and antisense morpholino
      oligonucleotide (target site) selection. Submitted sequences are analyzed by
      translation initiation site prediction algorithms and sequence-to-sequence
      comparisons; results are used to characterize sequence features required for
      morpholino design. Within a defined subsequence, base composition and
      homodimerization values are computed for all putative morpholino
      oligonucleotides. Using these properties, morpholino candidates are selected and
      compared with genomic and transcriptome databases with the goal to identify
      target-specific enriched morpholinos. AMOD has been used at the University of
      Minnesota to design approximately 200 morpholinos for a functional genomics
      screen in zebrafish. The AMOD web server and a tutorial are freely available to
      both academic and commercial users at http://www.secretomes.umn.edu/AMOD/.

PMID- 15980524
TI  - GENSTYLE: exploration and analysis of DNA sequences with genomic signature.
AB  - GENSTYLE (http://Genstyle.imed.jussieu.fr) is a workspace designed for the
      characterization and classification of nucleotide sequences. Based on the genomic
      signature paradigm, GENSTYLE focuses on oligonucleotide frequencies in DNA
      sequences. Users can select sequences of interest in the GENSTYLE companion
      database, where the whole set of GenBank sequences is grouped per species, or
      upload their own sequences to work with. Tools for the exploration and analysis
      of signatures allow (i) identification of the origin of DNA segments (detection
      of rare species or species for which technical problems prevent fast
      characterization, such as micro-organisms with slow growth), (ii) analysis of the
      homogeneity of a genome and isolation of areas with novel functionality
      (horizontal transfers for example)--and (iii) molecular phylogeny and taxonomy.

PMID- 15980525
TI  - PriFi: using a multiple alignment of related sequences to find primers for
      amplification of homologs.
AB  - Using a comparative approach, the web program PriFi (http://cgi
      www.daimi.au.dk/cgi-chili/PriFi/main) designs pairs of primers useful for PCR
      amplification of genomic DNA in species where prior sequence information is not
      available. The program works with an alignment of DNA sequences from
      phylogenetically related species and outputs a list of possibly degenerate primer
      pairs fulfilling a number of criteria, such that the primers have a maximal
      probability of amplifying orthologous sequences in other phylogenetically related
      species. Operating on a genome-wide scale, PriFi automates the first steps of a
      procedure for developing general markers serving as common anchor loci across
      species. To accommodate users with special preferences, configuration settings
      and criteria can be customized.

PMID- 15980526
TI  - Assembly PCR oligo maker: a tool for designing oligodeoxynucleotides for
      constructing long DNA molecules for RNA production.
AB  - We describe a computer program, Assembly PCR Oligo Maker, created to automate the
      design of oligodeoxynucleotides for the PCR-based construction of long DNA
      molecules. This program is freely available at
      http://publish.yorku.ca/~pjohnson/AssemblyPCRoligomaker.html and has been
      specifically designed to aid in the construction of DNA molecules that are to be
      used for the production of RNA molecules by in vitro synthesis with T7 RNA
      polymerase. The input for Assembly PCR Oligo Maker is either the desired DNA
      sequence to be made or an RNA sequence. If RNA is the input, the program first
      determines the DNA sequence necessary to produce the desired RNA molecule. The
      program then determines the sequences of all the oligodeoxynucleotides necessary
      for a two-step assembly PCR-based synthesis of the desired DNA molecule. The
      oligodeoxynucleotide sequences outputted are designed to have a uniform melt
      temperature and are checked for regions of overlap outside of the desired priming
      regions necessary for the PCR reaction. The validity of the program was verified
      experimentally by synthesizing a 191-nt long DNA molecule using the DNA sequences
      suggested by the program.

PMID- 15980527
TI  - JCat: a novel tool to adapt codon usage of a target gene to its potential
      expression host.
AB  - A novel method for the adaptation of target gene codon usage to most sequenced
      prokaryotes and selected eukaryotic gene expression hosts was developed to
      improve heterologous protein production. In contrast to existing tools, JCat
      (Java Codon Adaptation Tool) does not require the manual definition of highly
      expressed genes and is, therefore, a very rapid and easy method. Further options
      of JCat for codon adaptation include the avoidance of unwanted cleavage sites for
      restriction enzymes and Rho-independent transcription terminators. The output of
      JCat is both graphically and as Codon Adaptation Index (CAI) values given for the
      pasted sequence and the newly adapted sequence. Additionally, a list of genes in
      FASTA-format can be uploaded to calculate CAI values. In one example, all genes
      of the genome of Caenorhabditis elegans were adapted to Escherichia coli codon
      usage and further optimized to avoid commonly used restriction sites. In a second
      example, the Pseudomonas aeruginosa exbD gene codon usage was adapted to E.coli
      codon usage with parallel avoidance of the same restriction sites. For both, the
      degree of introduced changes was documented and evaluated. JCat is integrated
      into the PRODORIC database that hosts all required information on the various
      organisms to fulfill the requested calculations. JCat is freely accessible at
      http://www.prodoric.de/JCat.

PMID- 15980528
TI  - Multiple alignment of genomic sequences using CHAOS, DIALIGN and ABC.
AB  - Comparative analysis of genomic sequences is a powerful approach to discover
      functional sites in these sequences. Herein, we present a WWW-based software
      system for multiple alignment of genomic sequences. We use the local alignment
      tool CHAOS to rapidly identify chains of pairwise similarities. These
      similarities are used as anchor points to speed up the DIALIGN multiple-alignment
      program. Finally, the visualization tool ABC is used for interactive graphical
      representation of the resulting multiple alignments. Our software is available at
      Gottingen Bioinformatics Compute Server (GOBICS) at
      http://dialign.gobics.de/chaos-dialign-submission.

PMID- 15980529
TI  - PARALIGN: rapid and sensitive sequence similarity searches powered by parallel
      computing technology.
AB  - PARALIGN is a rapid and sensitive similarity search tool for the identification
      of distantly related sequences in both nucleotide and amino acid sequence
      databases. Two algorithms are implemented, accelerated Smith-Waterman and
      ParAlign. The ParAlign algorithm is similar to Smith-Waterman in sensitivity,
      while as quick as BLAST for protein searches. A form of parallel computing
      technology known as multimedia technology that is available in modern processors,
      but rarely used by other bioinformatics software, has been exploited to achieve
      the high speed. The software is also designed to run efficiently on computer
      clusters using the message-passing interface standard. A public search service
      powered by a large computer cluster has been set-up and is freely available at
      www.paralign.org, where the major public databases can be searched. The software
      can also be downloaded free of charge for academic use.

PMID- 15980530
TI  - YASS: enhancing the sensitivity of DNA similarity search.
AB  - YASS is a DNA local alignment tool based on an efficient and sensitive filtering
      algorithm. It applies transition-constrained seeds to specify the most probable
      conserved motifs between homologous sequences, combined with a flexible hit
      criterion used to identify groups of seeds that are likely to exhibit significant
      alignments. A web interface (http://www.loria.fr/projects/YASS/) is available to
      upload input sequences in fasta format, query the program and visualize the
      results obtained in several forms (dot-plot, tabular output and others). A
      standalone version is available for download from the web page.

PMID- 15980531
TI  - MuPlex: multi-objective multiplex PCR assay design.
AB  - We have developed a web-enabled system called MuPlex that aids researchers in the
      design of multiplex PCR assays. Multiplex PCR is a key technology for an endless
      list of applications, including detecting infectious microorganisms, whole-genome
      sequencing and closure, forensic analysis and for enabling flexible yet low-cost
      genotyping. However, the design of a multiplex PCR assays is computationally
      challenging because it involves tradeoffs among competing objectives, and
      extensive computational analysis is required in order to screen out primer-pair
      cross interactions. With MuPlex, users specify a set of DNA sequences along with
      primer selection criteria, interaction parameters and the target multiplexing
      level. MuPlex designs a set of multiplex PCR assays designed to cover as many of
      the input sequences as possible. MuPlex provides multiple solution alternatives
      that reveal tradeoffs among competing objectives. MuPlex is uniquely designed for
      large-scale multiplex PCR assay design in an automated high-throughput
      environment, where high coverage of potentially thousands of single nucleotide
      polymorphisms is required. The server is available at
      http://genomics14.bu.edu:8080/MuPlex/MuPlex.html.

PMID- 15980532
TI  - SOP3v2: web-based selection of oligonucleotide primer trios for genotyping of
      human and mouse polymorphisms.
AB  - SOP3v2 is a database-driven graphical web-based application for facilitating
      genotyping assay design. SOP3v2 accepts data input in numerous forms, including
      gene names, reference sequence numbers and physical location. For each entry, the
      application presents a set of recommended forward and reverse PCR primers, along
      with a sequencing primer, which is optimized for sequence-based genotyping
      assays. SOP3v2-generated oligonucleotide primer trios enable analysis of single
      nucleotide polymorphisms (SNPs) as well as insertion/deletion polymorphisms found
      in genomic DNA. The application's database was generated by warehousing
      information from the National Center for Biotechnology Information (NCBI) dbSNP
      database, genomic DNA sequences from human and mouse, and LocusLink gene
      attribute information. Query results can be sorted by their biological relevance,
      such as nonsynonymous coding changes or physical location. Human polymorphism
      queries may specify ethnicity, haplotype and validation status. Primers are
      developed using SOP3v2's core algorithm for evaluating primer candidates through
      stability tests and are suitable for use with sequence-based genotyping methods
      requiring locus-specific amplification. The method has undergone laboratory
      validation. Of the SOP3v2-designed primer trios that were tested, a majority
      (>80%) have successfully produced genotyping data. The application may be
      accessed via the web at http://imgen.ccbb.pitt.edu/sop3v2.

PMID- 15980533
TI  - POWER: PhylOgenetic WEb Repeater--an integrated and user-optimized framework for
      biomolecular phylogenetic analysis.
AB  - POWER, the PhylOgenetic WEb Repeater, is a web-based service designed to perform
      user-friendly pipeline phylogenetic analysis. POWER uses an open-source LAMP
      structure and infers genetic distances and phylogenetic relationships using well
      established algorithms (ClustalW and PHYLIP). POWER incorporates a novel tree
      builder based on the GD library to generate a high-quality tree topology
      according to the calculated result. POWER accepts either raw sequences in FASTA
      format or user-uploaded alignment output files. Through a user-friendly web
      interface, users can sketch a tree effortlessly in multiple steps. After a tree
      has been generated, users can freely set and modify parameters, select tree
      building algorithms, refine sequence alignments or edit the tree topology. All
      the information related to input sequences and the processing history is logged
      and downloadable for the user's reference. Furthermore, iterative tree
      construction can be performed by adding sequences to, or removing them from, a
      previously submitted job. POWER is accessible at http://power.nhri.org.tw.

PMID- 15980534
TI  - PHYML Online--a web server for fast maximum likelihood-based phylogenetic
      inference.
AB  - PHYML Online is a web interface to PHYML, a software that implements a fast and
      accurate heuristic for estimating maximum likelihood phylogenies from DNA and
      protein sequences. This tool provides the user with a number of options, e.g.
      nonparametric bootstrap and estimation of various evolutionary parameters, in
      order to perform comprehensive phylogenetic analyses on large datasets in
      reasonable computing time. The server and its documentation are available at
      http://atgc.lirmm.fr/phyml.

PMID- 15980535
TI  - Dcode.org anthology of comparative genomic tools.
AB  - Comparative genomics provides the means to demarcate functional regions in
      anonymous DNA sequences. The successful application of this method to identifying
      novel genes is currently shifting to deciphering the non-coding encryption of
      gene regulation across genomes. To facilitate the practical application of
      comparative sequence analysis to genetics and genomics, we have developed several
      analytical and visualization tools for the analysis of arbitrary sequences and
      whole genomes. These tools include two alignment tools, zPicture and Mulan; a
      phylogenetic shadowing tool, eShadow for identifying lineage- and species
      specific functional elements; two evolutionary conserved transcription factor
      analysis tools, rVista and multiTF; a tool for extracting cis-regulatory modules
      governing the expression of co-regulated genes, Creme 2.0; and a dynamic portal
      to multiple vertebrate and invertebrate genome alignments, the ECR Browser. Here,
      we briefly describe each one of these tools and provide specific examples on
      their practical applications. All the tools are publicly available at the
      http://www.dcode.org/ website.

PMID- 15980536
TI  - Projector 2: contig mapping for efficient gap-closure of prokaryotic genome
      sequence assemblies.
AB  - With genome sequencing efforts increasing exponentially, valuable information
      accumulates on genomic content of the various organisms sequenced. Projector 2
      uses (un)finished genomic sequences of an organism as a template to infer linkage
      information for a genome sequence assembly of a related organism being sequenced.
      The remaining gaps between contigs for which no linkage information is present
      can subsequently be closed with direct PCR strategies. Compared with other
      implementations, Projector 2 has several distinctive features: a user-friendly
      web interface, automatic removal of repetitive elements (repeat-masking) and
      automated primer design for gap-closure purposes. Moreover, when using multiple
      fragments of a template genome, primers for multiplex PCR strategies can also be
      designed. Primer design takes into account that, in many cases, contig ends
      contain unreliable DNA sequences and repetitive sequences. Closing the remaining
      gaps in prokaryotic genome sequence assemblies is thereby made very efficient and
      virtually effortless. We demonstrate that the use of single or multiple fragments
      of a template genome (i.e. unfinished genome sequences) in combination with
      repeat-masking results in mapping success rates close to 100%. The web interface
      is freely accessible at http://molgen.biol.rug.nl/websoftware/projector2.

PMID- 15980537
TI  - FeatureExtract--extraction of sequence annotation made easy.
AB  - Work on a large number of biological problems benefits tremendously from having
      an easy way to access the annotation of DNA sequence features, such as
      intron/exon structure, the contents of promoter regions and the location of other
      genes in upsteam and downstream regions. For example, taking the placement of
      introns within a gene into account can help in a phylogenetic analysis of
      homologous genes. Designing experiments for investigating UTR regions using PCR
      or DNA microarrays require knowledge of known elements in UTR regions and the
      positions and strandness of other genes nearby on the chromosome. A wealth of
      such information is already known and documented in databases such as GenBank and
      the NCBI Human Genome builds. However, it usually requires significant
      bioinformatics skills and intimate knowledge of the data format to access this
      information. Presented here is a highly flexible and easy-to-use tool for
      extracting feature annotation from GenBank entries. The tool is also useful for
      extracting datasets corresponding to a particular feature (e.g. promoters). Most
      importantly, the output data format is highly consistent, easy to handle for the
      user and easy to parse computationally. The FeatureExtract web server is freely
      available for both academic and commercial use at
      http://www.cbs.dtu.dk/services/FeatureExtract/.

PMID- 15980538
TI  - dnaMATE: a consensus melting temperature prediction server for short DNA
      sequences.
AB  - An accurate and robust large-scale melting temperature prediction server for
      short DNA sequences is dispatched. The server calculates a consensus melting
      temperature value using the nearest-neighbor model based on three independent
      thermodynamic data tables. The consensus method gives an accurate prediction of
      melting temperature, as it has been recently demonstrated in a benchmark
      performed using all available experimental data for DNA sequences within the
      length range of 16-30 nt. This constitutes the first web server that has been
      implemented to perform a large-scale calculation of melting temperatures in real
      time (up to 5000 DNA sequences can be submitted in a single run). The expected
      accuracy of calculations carried out by this server in the range of 50-600 mM
      monovalent salt concentration is that 89% of the melting temperature predictions
      will have an error or deviation of <5 degrees C from experimental data. The
      server can be freely accessed at http://dna.bio.puc.cl/tm.html. The standalone
      executable versions of this software for LINUX, Macintosh and Windows platforms
      are also freely available at the same web site. Detailed further information
      supporting this server is available at the same web site referenced above.

PMID- 15980539
TI  - Stitchprofiles.uio.no: analysis of partly melted DNA conformations using stitch
      profiles.
AB  - In this study, we describe a web server that performs computations on DNA
      melting, thus predicting the localized separation of the two strands for
      sequences provided by the users. The output types are stitch profiles, melting
      curves, probability profiles, etc. Stitch profile diagrams visualize the ensemble
      of alternative conformations that DNA can adopt with different probabilities. For
      example, a stitch profile shows the possible loop openings in terms of their
      locations, sizes, probabilities and fluctuations at a given temperature.
      Sequences with lengths up to several tens or hundreds of kilobase pairs can be
      analysed. The tools are freely available at http://stitchprofiles.uio.no.

PMID- 15980540
TI  - DINAMelt web server for nucleic acid melting prediction.
AB  - The DINAMelt web server simulates the melting of one or two single-stranded
      nucleic acids in solution. The goal is to predict not just a melting temperature
      for a hybridized pair of nucleic acids, but entire equilibrium melting profiles
      as a function of temperature. The two molecules are not required to be
      complementary, nor must the two strand concentrations be equal. Competition among
      different molecular species is automatically taken into account. Calculations
      consider not only the heterodimer, but also the two possible homodimers, as well
      as the folding of each single-stranded molecule. For each of these five molecular
      species, free energies are computed by summing Boltzmann factors over every
      possible hybridized or folded state. For temperatures within a user-specified
      range, calculations predict species mole fractions together with the free energy,
      enthalpy, entropy and heat capacity of the ensemble. Ultraviolet (UV) absorbance
      at 260 nm is simulated using published extinction coefficients and computed base
      pair probabilities. All results are available as text files and plots are
      provided for species concentrations, heat capacity and UV absorbance versus
      temperature. This server is connected to an active research program and should
      evolve as new theory and software are developed. The server URL is
      http://www.bioinfo.rpi.edu/applications/hybrid/.

PMID- 15980541
TI  - E-RNAi: a web application to design optimized RNAi constructs.
AB  - RNA interference (RNAi) has become a powerful genetic approach to systematically
      dissect gene function on a genome-wide scale. Owing to the penetrance and
      efficiency of RNAi in invertebrates, model organisms such as Drosophila
      melanogaster and Caenorhabditis elegans have contributed significantly to the
      identification of novel components of diverse biological pathways, ranging from
      early development to fat storage and aging. For the correct assessment of
      phenotypes, a key issue remains the stringent quality control of long double
      stranded RNAs (dsRNA) to calculate potential off-target effects that may obscure
      the phenotypic data. We here describe a web-based tool to evaluate and design
      optimized dsRNA constructs. Moreover, the application also gives access to
      published predesigned dsRNAs. The E-RNAi web application is available at http://e
      rnai.dkfz.de/.

PMID- 15980542
TI  - dsCheck: highly sensitive off-target search software for double-stranded RNA
      mediated RNA interference.
AB  - Off-target effects are one of the most serious problems in RNA interference
      (RNAi). Here, we present dsCheck (http://dsCheck.RNAi.jp/), web-based online
      software for estimating off-target effects caused by the long double-stranded RNA
      (dsRNA) used in RNAi studies. In the biochemical process of RNAi, the long dsRNA
      is cleaved by Dicer into short-interfering RNA (siRNA) cocktails. The software
      simulates this process and investigates individual 19 nt substrings of the long
      dsRNA. Subsequently, the software promptly enumerates a list of potential off
      target gene candidates based on the order of off-target effects using its novel
      algorithm, which significantly improves both the efficiency and the sensitivity
      of the homology search. The website not only provides a rigorous off-target
      search to verify previously designed dsRNA sequences but also presents 'off
      target minimized' dsRNA design, which is essential for reliable experiments in
      RNAi-based functional genomics.

PMID- 15980543
TI  - T-profiler: scoring the activity of predefined groups of genes using gene
      expression data.
AB  - One of the key challenges in the analysis of gene expression data is how to
      relate the expression level of individual genes to the underlying transcriptional
      programs and cellular state. Here we describe T-profiler, a tool that uses the t
      test to score changes in the average activity of predefined groups of genes. The
      gene groups are defined based on Gene Ontology categorization, ChIP-chip
      experiments, upstream matches to a consensus transcription factor binding motif
      or location on the same chromosome. If desired, an iterative procedure can be
      used to select a single, optimal representative from sets of overlapping gene
      groups. T-profiler makes it possible to interpret microarray data in a way that
      is both intuitive and statistically rigorous, without the need to combine
      experiments or choose parameters. Currently, gene expression data from
      Saccharomyces cerevisiae and Candida albicans are supported. Users can upload
      their microarray data for analysis on the web at http://www.t-profiler.org.

PMID- 15980544
TI  - GEMS: a web server for biclustering analysis of expression data.
AB  - The advent of microarray technology has revolutionized the search for genes that
      are differentially expressed across a range of cell types or experimental
      conditions. Traditional clustering methods, such as hierarchical clustering, are
      often difficult to deploy effectively since genes rarely exhibit similar
      expression pattern across a wide range of conditions. Biclustering of gene
      expression data (also called co-clustering or two-way clustering) is a non
      trivial but promising methodology for the identification of gene groups that show
      a coherent expression profile across a subset of conditions. Thus, biclustering
      is a natural methodology as a screen for genes that are functionally related,
      participate in the same pathways, affected by the same drug or pathological
      condition, or genes that form modules that are potentially co-regulated by a
      small group of transcription factors. We have developed a web-enabled service
      called GEMS (Gene Expression Mining Server) for biclustering microarray data.
      Users may upload expression data and specify a set of criteria. GEMS then
      performs bicluster mining based on a Gibbs sampling paradigm. The web server
      provides a flexible and an useful platform for the discovery of co-expressed and
      potentially co-regulated gene modules. GEMS is an open source software and is
      available at http://genomics10.bu.edu/terrence/gems/.

PMID- 15980545
TI  - RNALOSS: a web server for RNA locally optimal secondary structures.
AB  - RNAomics, analogous to proteomics, concerns aspects of the secondary and tertiary
      structure, folding pathway, kinetics, comparison, function and regulation of all
      RNA in a living organism. Given recently discovered roles played by micro RNA,
      small interfering RNA, riboswitches, ribozymes, etc., it is important to gain
      insight into the folding process of RNA sequences. We describe the web server
      RNALOSS, which provides information about the distribution of locally optimal
      secondary structures, that possibly form kinetic traps in the folding process.
      The tool RNALOSS may be useful in designing RNA sequences which not only have low
      folding energy, but whose distribution of locally optimal secondary structures
      would suggest rapid and robust folding. Website:
      http://clavius.bc.edu/~clotelab/RNALOSS/.

PMID- 15980546
TI  - Kinefold web server for RNA/DNA folding path and structure prediction including
      pseudoknots and knots.
AB  - The Kinefold web server provides a web interface for stochastic folding
      simulations of nucleic acids on second to minute molecular time scales.
      Renaturation or co-transcriptional folding paths are simulated at the level of
      helix formation and dissociation in agreement with the seminal experimental
      results. Pseudoknots and topologically 'entangled' helices (i.e. knots) are
      efficiently predicted taking into account simple geometrical and topological
      constraints. To encourage interactivity, simulations launched as immediate jobs
      are automatically stopped after a few seconds and return adapted recommendations.
      Users can then choose to continue incomplete simulations using the batch queuing
      system or go back and modify suggested options in their initial query. Detailed
      output provide (i) a series of low free energy structures, (ii) an online
      animated folding path and (iii) a programmable trajectory plot focusing on a few
      helices of interest to each user. The service can be accessed at
      http://kinefold.curie.fr/.

PMID- 15980547
TI  - OligoWiz 2.0--integrating sequence feature annotation into the design of
      microarray probes.
AB  - OligoWiz 2.0 is a powerful tool for microarray probe design that allows for
      integration of sequence annotation, such as exon/intron structure, untranslated
      regions (UTRs), transcription start site, etc. In addition to probe selection
      according to a series of probe quality parameters, cross-hybridization, T(m),
      position in transcript, probe folding and low-complexity, the program facilitates
      automatic placement of probes relative to the sequence annotation. The program
      also supports automatic placement of multiple probes per transcript. Together
      these facilities make advanced probe design feasible for scientists inexperienced
      in computerized information management. Furthermore, we show that probes designed
      using OligoWiz 2.0 give rise to consistent hybridization results
      (http://www.cbs.dtu.dk/services/OligoWiz2).

PMID- 15980548
TI  - GEPAS, an experiment-oriented pipeline for the analysis of microarray gene
      expression data.
AB  - The Gene Expression Profile Analysis Suite, GEPAS, has been running for more than
      three years. With >76,000 experiments analysed during the last year and a daily
      average of almost 300 analyses, GEPAS can be considered a well-established and
      widely used platform for gene expression microarray data analysis. GEPAS is
      oriented to the analysis of whole series of experiments. Its design and
      development have been driven by the demands of the biomedical community, probably
      the most active collective in the field of microarray users. Although clustering
      methods have obviously been implemented in GEPAS, our interest has focused more
      on methods for finding genes differentially expressed among distinct classes of
      experiments or correlated to diverse clinical outcomes, as well as on building
      predictors. There is also a great interest in CGH-arrays which fostered the
      development of the corresponding tool in GEPAS: InSilicoCGH. Much effort has been
      invested in GEPAS for developing and implementing efficient methods for
      functional annotation of experiments in the proper statistical framework. Thus,
      the popular FatiGO has expanded to a suite of programs for functional annotation
      of experiments, including information on transcription factor binding sites,
      chromosomal location and tissues. The web-based pipeline for microarray gene
      expression data, GEPAS, is available at http://www.gepas.org.

PMID- 15980549
TI  - ArrayXPath II: mapping and visualizing microarray gene-expression data with
      biomedical ontologies and integrated biological pathway resources using Scalable
      Vector Graphics.
AB  - SUMMARY: ArrayXPath (http://www.snubi.org/software/ArrayXPath/) is a web-based
      service for mapping and visualizing microarray gene-expression data with
      integrated biological pathway resources using Scalable Vector Graphics (SVG).
      Deciphering the crosstalk among pathways and integrating biomedical ontologies
      and knowledge bases may help biological interpretation of microarray data.
      ArrayXPath is empowered by integrating gene-pathway, disease-pathway, drug
      pathway and pathway-pathway correlations with integrated Gene Ontology, Medical
      Subject Headings and OMIM Morbid Map-based annotations. We applied Fisher's exact
      test and relative risk to evaluate the statistical significance of the
      correlations. ArrayXPath produces Javascript-enabled SVGs for web-enabled
      interactive visualization of gene-expression profiles integrated with gene
      pathway-disease interactions enriched by biomedical ontologies.

PMID- 15980550
TI  - VAMPIRE microarray suite: a web-based platform for the interpretation of gene
      expression data.
AB  - Microarrays are invaluable high-throughput tools used to snapshot the gene
      expression profiles of cells and tissues. Among the most basic and fundamental
      questions asked of microarray data is whether individual genes are significantly
      activated or repressed by a particular stimulus. We have previously presented two
      Bayesian statistical methods for this level of analysis, collectively known as
      variance-modeled posterior inference with regional exponentials (VAMPIRE). These
      methods each require a sophisticated modeling step followed by integration of a
      posterior probability density. We present here a publicly available, web-based
      platform that allows users to easily load data, associate related samples and
      identify differentially expressed features using the VAMPIRE statistical
      framework. In addition, this suite of tools seamlessly integrates a novel gene
      annotation tool, known as GOby, which identifies statistically overrepresented
      gene groups. Unlike other tools in this genre, GOby can localize enrichment while
      respecting the hierarchical structure of annotation systems like Gene Ontology
      (GO). By identifying statistically significant enrichment of GO terms, Kyoto
      Encyclopedia of Genes and Genomes pathways, and TRANSFAC transcription factor
      binding sites, users can gain substantial insight into the physiological
      significance of sets of differentially expressed genes. The VAMPIRE microarray
      suite can be accessed at http://genome.ucsd.edu/microarray.

PMID- 15980551
TI  - PathwayExplorer: web service for visualizing high-throughput expression data on
      biological pathways.
AB  - While generation of high-throughput expression data is becoming routine, the
      fast, easy, and systematic presentation and analysis of these data in a
      biological context is still an obstacle. To address this need, we have developed
      PathwayExplorer, which maps expression profiles of genes or proteins
      simultaneously onto major, currently available regulatory, metabolic and cellular
      pathways from KEGG, BioCarta and GenMAPP. PathwayExplorer is a platform
      independent web server application with an optional standalone Java application
      using a SOAP (simple object access protocol) interface. Mapped pathways are
      ranked for the easy selection of the pathway of interest, displaying all
      available genes of this pathway with their expression profiles in a selectable
      and intuitive color code. Pathway maps produced can be downloaded as PNG, JPG or
      as high-resolution vector graphics SVG. The web service is freely available at
      https://pathwayexplorer.genome.tugraz.at; the standalone client can be downloaded
      at http://genome.tugraz.at.

PMID- 15980552
TI  - RACE: Remote Analysis Computation for gene Expression data.
AB  - The Remote Analysis Computation for gene Expression data (RACE) suite is a
      collection of bioinformatics web tools designed for the analysis of DNA
      microarray data. RACE performs probe-level data preprocessing, extensive quality
      checks, data visualization and data normalization for Affymetrix GeneChips. In
      addition, it offers differential expression analysis on normalized expression
      levels from any array platform. RACE estimates the false discovery rates of lists
      of potentially regulated genes and provides a Gene Ontology-term analysis tool
      for GeneChip data to support the biological interpretation and annotation of
      results. The analysis is fully automated but can be customized by flexible
      parameter settings. To offer a convenient starting point for subsequent analyses,
      and to provide maximum transparency, the R scripts used to generate the results
      can be downloaded along with the output files. RACE is freely available for use
      at http://race.unil.ch.

PMID- 15980553
TI  - MIDAW: a web tool for statistical analysis of microarray data.
AB  - MIDAW (microarray data analysis web tool) is a web interface integrating a series
      of statistical algorithms that can be used for processing and interpretation of
      microarray data. MIDAW consists of two main sections: data normalization and data
      analysis. In the normalization phase the simultaneous processing of several
      experiments with background correction, global and local mean and variance
      normalization are carried out. The data analysis section allows graphical display
      of expression data for descriptive purposes, estimation of missing values,
      reduction of data dimension, discriminant analysis and identification of marker
      genes. The statistical results are organized in dynamic web pages and tables,
      where the transcript/gene probes contained in a specific microarray platform can
      be linked (according to user choice) to external databases (GenBank, Entrez Gene,
      UniGene). Tutorial files help the user throughout the statistical analysis to
      ensure that the forms are filled out correctly. MIDAW has been developed using
      Perl and PHP and it uses R/Bioconductor languages and routines. MIDAW is GPL
      licensed and freely accessible at http://muscle.cribi.unipd.it/midaw/. Perl and
      PHP source codes are available from the authors upon request.

PMID- 15980554
TI  - PAT: a protein analysis toolkit for integrated biocomputing on the web.
AB  - PAT, for Protein Analysis Toolkit, is an integrated biocomputing server. The main
      goal of its design was to facilitate the combination of different processing
      tools for complex protein analyses and to simplify the automation of repetitive
      tasks. The PAT server provides a standardized web interface to a wide range of
      protein analysis tools. It is designed as a streamlined analysis environment that
      implements many features which strongly simplify studies dealing with protein
      sequences and structures and improve productivity. PAT is able to read and write
      data in many bioinformatics formats and to create any desired pipeline by
      seamlessly sending the output of a tool to the input of another tool. PAT can
      retrieve protein entries from identifier-based queries by using pre-computed
      database indexes. Users can easily formulate complex queries combining different
      analysis tools with few mouse clicks, or via a dedicated macro language, and a
      web session manager provides direct access to any temporary file generated during
      the user session. PAT is freely accessible on the Internet at
      http://pat.cbs.cnrs.fr.

PMID- 15980555
TI  - The FOLDALIGN web server for pairwise structural RNA alignment and mutual motif
      search.
AB  - Foldalign is a Sankoff-based algorithm for making structural alignments of RNA
      sequences. Here, we present a web server for making pairwise alignments between
      two RNA sequences, using the recently updated version of foldalign. The server
      can be used to scan two sequences for a common structural RNA motif of limited
      size, or the entire sequences can be aligned locally or globally. The web server
      offers a graphical interface, which makes it simple to make alignments and
      manually browse the results. The web server can be accessed at
      http://foldalign.kvl.dk.

PMID- 15980556
TI  - T-STAG: resource and web-interface for tissue-specific transcripts and genes.
AB  - T-STAG (tissue-specific transcripts and genes) is a resource and web-interface,
      designated to analyze tissue/tumor-specific expression patterns in human and
      mouse transcriptomes. It integrates our refined prediction of specific expression
      patterns both in genes as well as in individual isoforms with man-mouse orthology
      data. In combination with the features for combining/contrasting the genes
      expressed in different tissues, T-STAG implicates important biological
      applications, such as the detection of differentially expressed genes in tumors,
      the retrieval of orthologs with significant expression in the same tissue etc.
      Additionally, our refined categorization of expressed sequence tags (ESTs)
      according to the normalization of cDNA libraries allows searching for putative
      low-abundant transcripts. The results are tightly linked to our visualization
      tools, GeneNest (expression patterns of genes) and SpliceNest (gene structure and
      alternative splicing). The user-friendly interface of T-STAG offers a platform
      for comprehensive analysis of tissue and/or tumor-specific expression patterns
      revealed by the EST data. T-STAG is freely accessible at
      http://tstag.molgen.mpg.de.

PMID- 15980557
TI  - ASIAN: a web server for inferring a regulatory network framework from gene
      expression profiles.
AB  - The standard workflow in gene expression profile analysis to identify gene
      function is the clustering by various metrics and techniques, and the following
      analyses, such as sequence analyses of upstream regions. A further challenging
      analysis is the inference of a gene regulatory network, and some computational
      methods have been intensively developed to deduce the gene regulatory network.
      Here, we describe our web server for inferring a framework of regulatory networks
      from a large number of gene expression profiles, based on graphical Gaussian
      modeling (GGM) in combination with hierarchical clustering (http://eureka.ims.u
      tokyo.ac.jp/asian). GGM is based on a simple mathematical structure, which is the
      calculation of the inverse of the correlation coefficient matrix between
      variables, and therefore, our server can analyze a wide variety of data within a
      reasonable computational time. The server allows users to input the expression
      profiles, and it outputs the dendrogram of genes by several hierarchical
      clustering techniques, the cluster number estimated by a stopping rule for
      hierarchical clustering and the network between the clusters by GGM, with the
      respective graphical presentations. Thus, the ASIAN (Automatic System for
      Inferring A Network) web server provides an initial basis for inferring
      regulatory relationships, in that the clustering serves as the first step toward
      identifying the gene function.

PMID- 15980558
TI  - AntiHunter 2.0: increased speed and sensitivity in searching BLAST output for EST
      antisense transcripts.
AB  - An increasing number of eukaryotic and prokaryotic genes are being found to have
      natural antisense transcripts (NATs). There is also growing evidence to suggest
      that antisense transcription could play a key role in many human diseases.
      Consequently, there have been several recent attempts to set up computational
      procedures aimed at identifying novel NATs. Our group has developed the
      AntiHunter program for the identification of expressed sequence tag (EST)
      antisense transcripts from BLAST output. In order to perform an analysis, the
      program requires a genomic sequence plus an associated list of transcript names
      and coordinates of the genomic region. After masking the repeated regions, the
      program carries out a BLASTN search of this sequence in the selected EST
      database, reporting via email the EST entries that reveal an antisense transcript
      according to the user-supplied list. Here, we present the newly developed version
      2.0 of the AntiHunter tool. Several improvements have been added to this version
      of the program in order to increase its ability to detect a larger number of
      antisense ESTs. As a result, AntiHunter can now detect, on average, >45% more
      antisense ESTs with little or no increase in the percentage of the false
      positives. We also raised the maximum query size to 3 Mb (previously 1 Mb).
      Moreover, we found that a reasonable trade-off between the program search
      sensitivity and the maximum allowed size of the input-query sequence could be
      obtained by querying the database with the MEGABLAST program, rather than by
      using the BLAST one. We now offer this new opportunity to users, i.e. if choosing
      the MEGABLAST option, users can input a query sequence up to 30 Mb long, thus
      considerably improving the possibility to analyze longer query regions. The
      AntiHunter tool is freely available at http://bioinfo.crs4.it/AH2.0.

PMID- 15980559
TI  - TargetIdentifier: a webserver for identifying full-length cDNAs from EST
      sequences.
AB  - TargetIdentifier is a webserver that identifies full-length cDNA sequences from
      the expressed sequence tag (EST)-derived contig and singleton data. To accomplish
      this TargetIdentifier uses BLASTX alignments as a guide to locate protein coding
      regions and potential start and stop codons. This information is then used to
      determine whether the EST-derived sequences include their translation start
      codons. The algorithm also uses the BLASTX output to assign putative functions to
      the query sequences. The server is available at
      https://fungalgenome.concordia.ca/tools/TargetIdentifier.html.

PMID- 15980560
TI  - GBA server: EST-based digital gene expression profiling.
AB  - Expressed Sequence Tag-based gene expression profiling can be used to discover
      functionally associated genes on a large scale. Currently available web servers
      and tools focus on finding differentially expressed genes in different samples or
      tissues rather than finding co-expressed genes. To fill this gap, we have
      developed a web server that implements the GBA (Guilt-by-Association) co
      expression algorithm, which has been successfully used in finding disease-related
      genes. We have also annotated UniGene clusters with links to several important
      databases such as GO, KEGG, OMIM, Gene, IPI and HomoloGene. The GBA server can be
      accessed and downloaded at http://gba.cbi.pku.edu.cn.

PMID- 15980561
TI  - OrfPredictor: predicting protein-coding regions in EST-derived sequences.
AB  - OrfPredictor is a web server designed for identifying protein-coding regions in
      expressed sequence tag (EST)-derived sequences. For query sequences with a hit in
      BLASTX, the program predicts the coding regions based on the translation reading
      frames identified in BLASTX alignments, otherwise, it predicts the most probable
      coding region based on the intrinsic signals of the query sequences. The output
      is the predicted peptide sequences in the FASTA format, and a definition line
      that includes the query ID, the translation reading frame and the nucleotide
      positions where the coding region begins and ends. OrfPredictor facilitates the
      annotation of EST-derived sequences, particularly, for large-scale EST projects.
      OrfPredictor is available at
      https://fungalgenome.concordia.ca/tools/OrfPredictor.html.

PMID- 15980562
TI  - ASePCR: alternative splicing electronic RT-PCR in multiple tissues and organs.
AB  - RT-PCR is one of the most powerful and direct methods to detect transcript
      variants due to alternative splicing (AS) that increase transcript diversity
      significantly in vertebrates. ASePCR is an efficient web-based application that
      emulates RT-PCR in various tissues. It estimates the amplicon size for a given
      primer pair based on the transcript models identified by the reverse e-PCR
      program of the NCBI. The tissue specificity of each PCR band is deduced from the
      tissue information of expressed sequence tag (EST) sequences compatible with each
      transcript structure. The output page shows PCR bands like a gel electrophoresis
      in various tissues. Each band in the output picture represents a putative isoform
      that could happen in a tissue-specific manner. It also shows the EST alignment
      and tissue information in the genome browser. Furthermore, the user can compare
      the AS patterns of orthologous genes in other species. The ASePCR, available at
      http://genome.ewha.ac.kr/ASePCR/, supports the transcriptome models of the
      RefSeq, Ensembl, ECgene and AceView for human, mouse, rat and chicken genomes. It
      will be a valuable web resource to explore the transcriptome diversity associated
      with different tissues and organs in multiple species.

PMID- 15980563
TI  - The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and
      snoRNAs.
AB  - Transfer RNAs (tRNAs) and small nucleolar RNAs (snoRNAs) are two of the largest
      classes of non-protein-coding RNAs. Conventional gene finders that detect protein
      coding genes do not find tRNA and snoRNA genes because they lack the codon
      structure and statistical signatures of protein-coding genes. Previously, we
      developed tRNAscan-SE, snoscan and snoGPS for the detection of tRNAs, methylation
      guide snoRNAs and pseudouridylation-guide snoRNAs, respectively. tRNAscan-SE is
      routinely applied to completed genomes, resulting in the identification of
      thousands of tRNA genes. Snoscan has successfully detected methylation-guide
      snoRNAs in a variety of eukaryotes and archaea, and snoGPS has identified novel
      pseudouridylation-guide snoRNAs in yeast and mammals. Although these programs
      have been quite successful at RNA gene detection, their use has been limited by
      the need to install and configure the software packages on UNIX workstations.
      Here, we describe online implementations of these RNA detection tools that make
      these programs accessible to a wider range of research biologists. The tRNAscan
      SE, snoscan and snoGPS servers are available at http://lowelab.ucsc.edu/tRNAscan
      SE/, http://lowelab.ucsc.edu/snoscan/ and http://lowelab.ucsc.edu/snoGPS/,
      respectively.

PMID- 15980564
TI  - RibEx: a web server for locating riboswitches and other conserved bacterial
      regulatory elements.
AB  - We present RibEx (riboswitch explorer), a web server capable of searching any
      sequence for known riboswitches as well as other predicted, but highly conserved,
      bacterial regulatory elements. It allows the visual inspection of the identified
      motifs in relation to attenuators and open reading frames (ORFs). Any of the
      ORF's or regulatory elements' sequence can be obtained with a click and submitted
      to NCBI's BLAST. Alternatively, the genome context of all other genes regulated
      by the same element can be explored with our genome context tool (GeConT). RibEx
      is available at http://www.ibt.unam.mx/biocomputo/ribex.html.

PMID- 15980565
TI  - WEBSAGE: a web tool for visual analysis of differentially expressed human SAGE
      tags.
AB  - The serial analysis of gene expression (SAGE) is a powerful method to compare
      gene expression of mRNA populations. To provide quantitative expression levels on
      a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses SAGE. Over 7
      million SAGE tags, from 171 human cell types have been assembled. The growing
      number of laboratories involved in SAGE research necessitates the use of software
      that provides statistical analysis of raw data, allowing the rapid visualization
      and interpretation of results. We have created the first simple tool that
      performs statistical analysis on SAGE data, identifies the tags differentially
      expressed and shows the results in a scatter plot. It is freely available and
      accessible at http://bioserv.rpbs.jussieu.fr/websage/index.php.

PMID- 15980566
TI  - MicroInspector: a web tool for detection of miRNA binding sites in an RNA
      sequence.
AB  - Regulation of post-transcriptional gene expression by microRNAs (miRNA) has so
      far been validated for only a few mRNA targets. Based on the large number of
      miRNA genes and the possibility that one miRNA might influence gene expression of
      several targets simultaneously, the quantity of ribo-regulated genes is expected
      to be much higher. Here, we describe the web tool MicroInspector that will
      analyse a user-defined RNA sequence, which is typically an mRNA or a part of an
      mRNA, for the occurrence of binding sites for known and registered miRNAs. The
      program allows variation of temperature, the setting of energy values as well as
      the selection of different miRNA databases to identify miRNA-binding sites of
      different strength. MicroInspector could spot the correct sites for miRNA
      interaction in known target mRNAs. Using other mRNAs, for which such an
      interaction has not yet been described, we discovered frequently potential miRNA
      binding sites of similar quality, which can now be analysed experimentally. The
      MicroInspector program is easy to use and does not require specific computer
      skills. The service can be accessed via the MicroInspector web server at
      http://www.imbb.forth.gr/microinspector.

PMID- 15980567
TI  - miRU: an automated plant miRNA target prediction server.
AB  - MicroRNAs (miRNAs) play important roles in gene expression regulation in animals
      and plants. Since plant miRNAs recognize their target mRNAs by near-perfect base
      pairing, computational sequence similarity search can be used to identify
      potential targets. A web-based integrated computing system, miRU, has been
      developed for plant miRNA target gene prediction in any plant, if a large number
      of sequences are available. Given a mature miRNA sequence from a plant species,
      the system thoroughly searches for potential complementary target sites with
      mismatches tolerable in miRNA-target recognition. True or false positives are
      estimated based on the number and type of mismatches in the target site, and on
      the evolutionary conservation of target complementarity in another genome which
      can be selected according to miRNA conservation. The output for predicted
      targets, ordered by mismatch scores, includes complementary sequences with
      mismatches highlighted in colors, original gene sequences and associated
      functional annotations. The miRU web server is available at
      http://bioinfo3.noble.org/miRU.htm.

PMID- 15980568
TI  - AISMIG--an interactive server-side molecule image generator.
AB  - Using a web browser without additional software and generating interactive high
      quality and high resolution images of bio-molecules is no longer a problem.
      Interactive visualization of 3D molecule structures by Internet browsers normally
      is not possible without additional software and the disadvantage of browser-based
      structure images (e.g. by a Java applet) is their low resolution. Scientists who
      want to generate 3D molecular images with high quality and high resolution (e.g.
      for publications or to render a molecule for a poster) therefore require
      separately installed software that is often not easy to use. The alternative
      concept is an interactive server-side rendering application that can be
      interfaced with any web browser. Thus it combines the advantage of the web
      application with the high-end rendering of a raytracer. This article addresses
      users who want to generate high quality images from molecular structures and do
      not have software installed locally for structure visualization. Often people do
      not have a structure viewer, such as RasMol or Chime (or even Java) installed
      locally but want to visualize a molecule structure interactively. AISMIG (An
      Interactive Server-side Molecule Image Generator) is a web service that provides
      a visualization of molecule structures in such cases. AISMIG-URL: http://www.dkfz
      heidelberg.de/spec/aismig/.

PMID- 15980569
TI  - BRIGEP--the BRIDGE-based genome-transcriptome-proteome browser.
AB  - The growing amount of information resulting from the increasing number of
      publicly available genomes and experimental results thereof necessitates the
      development of comprehensive systems for data processing and analysis. In this
      paper, we describe the current state and latest developments of our BRIGEP
      bioinformatics software system consisting of three web-based applications: GenDB,
      EMMA and ProDB. These applications facilitate the processing and analysis of
      bacterial genome, transcriptome and proteome data and are actively used by
      numerous international groups. We are currently in the process of extensively
      interconnecting these applications. BRIGEP was developed in the Bioinformatics
      Resource Facility of the Center for Biotechnology at Bielefeld University and is
      freely available. A demo project with sample data and access to all three tools
      is available at https://www.cebitec.uni-bielefeld.de/groups/brf/software/brigep/.
      Code bundles for these and other tools developed in our group are accessible on
      our FTP server at ftp.cebitec.uni-bielefeld.de/pub/software/.

PMID- 15980570
TI  - GFINDer: genetic disease and phenotype location statistical analysis and mining
      of dynamically annotated gene lists.
AB  - Phenotype analysis is commonly recognized to be of great importance for gaining
      insight into genetic interaction underlying inherited diseases. However, few
      computational contributions have been proposed for this purpose, mainly owing to
      lack of controlled clinical information easily accessible and structured for
      computational genome-wise analyses. We developed and made available through
      GFINDer web server an original approach for the analysis of genetic disorder
      related genes by exploiting the information on genetic diseases and their
      clinical phenotypes present in textual form within the Online Mendelian
      Inheritance in Man (OMIM) database. Because several synonyms for the same name
      and different names for overlapping concepts are often used in OMIM, we first
      normalized phenotype location descriptions reducing them to a list of unique
      controlled terms representing phenotype location categories. Then, we
      hierarchically structured them and the correspondent genetic diseases according
      to their topology and granularity of description, respectively. Thus, in GFINDer
      we could implement specific Genetic Disorders modules for the analysis of these
      structured data. Such modules allow to automatically annotate user-classified
      gene lists with updated disease and clinical information, classify them according
      to the genetic syndrome and the phenotypic location categories, and statistically
      identify the most relevant categories in each gene class. GFINDer is available
      for non-profit use at http://www.bioinformatics.polimi.it/GFINDer/.

PMID- 15980571
TI  - SCRATCH: a protein structure and structural feature prediction server.
AB  - SCRATCH is a server for predicting protein tertiary structure and structural
      features. The SCRATCH software suite includes predictors for secondary structure,
      relative solvent accessibility, disordered regions, domains, disulfide bridges,
      single mutation stability, residue contacts versus average, individual residue
      contacts and tertiary structure. The user simply provides an amino acid sequence
      and selects the desired predictions, then submits to the server. Results are
      emailed to the user. The server is available at
      http://www.igb.uci.edu/servers/psss.html.

PMID- 15980572
TI  - Eclair--a web service for unravelling species origin of sequences sampled from
      mixed host interfaces.
AB  - The identification of the genes that participate at the biological interface of
      two species remains critical to our understanding of the mechanisms of disease
      resistance, disease susceptibility and symbiosis. The sequencing of complementary
      DNA (cDNA) libraries prepared from the biological interface between two organisms
      provides an inexpensive way to identify the novel genes that may be expressed as
      a cause or consequence of compatible or incompatible interactions. Sequence
      classification and annotation of species origin typically use an orthology-based
      approach and require access to large portions of either genome, or a close
      relative. Novel species- or clade-specific sequences may have no counterpart
      within existing databases and remain ambiguous features. Here we present a web
      service, Eclair, which utilizes support vector machines for the classification of
      the origin of expressed sequence tags stemming from mixed host cDNA libraries. In
      addition to providing an interface for the classification of sequences, users are
      presented with the opportunity to train a model to suit their preferred species
      pair. Eclair is freely available at http://eclair.btk.fi.

PMID- 15980573
TI  - The multilocus sequence typing network: mlst.net.
AB  - The unambiguous characterization of strains of a pathogen is crucial for
      addressing questions relating to its epidemiology, population and evolutionary
      biology. Multilocus sequence typing (MLST), which defines strains from the
      sequences at seven house-keeping loci, has become the method of choice for
      molecular typing of many bacterial and fungal pathogens (and non-pathogens), and
      MLST schemes and strain databases are available for a growing number of
      prokaryotic and eukaryotic organisms. Sequence data are ideal for strain
      characterization as they are unambiguous, meaning strains can readily be compared
      between laboratories via the Internet. Laboratories undertaking MLST can quickly
      progress from sequencing the seven gene fragments to characterizing their strains
      and relating them to those submitted by others and to the population as a whole.
      We provide the gateway to a number of MLST schemes, each of which contain a set
      of tools for the initial characterization of strains, and methods for relating
      query strains to other strains of the species, including clustering based on
      differences in allelic profiles, phylogenetic trees based on concatenated
      sequences, and a recently developed method (eBURST) for identifying clonal
      complexes within a species and displaying the overall structure of the
      population. This network of MLST websites is available at http://www.mlst.net.

PMID- 15980574
TI  - The bioinformatics resource for oral pathogens.
AB  - Complete genomic sequences of several oral pathogens have been deciphered and
      multiple sources of independently annotated data are available for the same
      genomes. Different gene identification schemes and functional annotation methods
      used in these databases present a challenge for cross-referencing and the
      efficient use of the data. The Bioinformatics Resource for Oral Pathogens (BROP)
      aims to integrate bioinformatics data from multiple sources for easy comparison,
      analysis and data-mining through specially designed software interfaces.
      Currently, databases and tools provided by BROP include: (i) a graphical genome
      viewer (Genome Viewer) that allows side-by-side visual comparison of
      independently annotated datasets for the same genome; (ii) a pipeline of
      automatic data-mining algorithms to keep the genome annotation always up-to-date;
      (iii) comparative genomic tools such as Genome-wide ORF Alignment (GOAL); and
      (iv) the Oral Pathogen Microarray Database. BROP can also handle unfinished
      genomic sequences and provides secure yet flexible control over data access. The
      concept of providing an integrated source of genomic data, as well as the data
      mining model used in BROP can be applied to other organisms. BROP can be publicly
      accessed at http://www.brop.org.

PMID- 15980575
TI  - WebGestalt: an integrated system for exploring gene sets in various biological
      contexts.
AB  - High-throughput technologies have led to the rapid generation of large-scale
      datasets about genes and gene products. These technologies have also shifted our
      research focus from 'single genes' to 'gene sets'. We have developed a web-based
      integrated data mining system, WebGestalt (http://genereg.ornl.gov/webgestalt/),
      to help biologists in exploring large sets of genes. WebGestalt is composed of
      four modules: gene set management, information retrieval,
      organization/visualization, and statistics. The management module uploads, saves,
      retrieves and deletes gene sets, as well as performs Boolean operations to
      generate the unions, intersections or differences between different gene sets.
      The information retrieval module currently retrieves information for up to 20
      attributes for all genes in a gene set. The organization/visualization module
      organizes and visualizes gene sets in various biological contexts, including Gene
      Ontology, tissue expression pattern, chromosome distribution, metabolic and
      signaling pathways, protein domain information and publications. The statistics
      module recommends and performs statistical tests to suggest biological areas that
      are important to a gene set and warrant further investigation. In order to
      demonstrate the use of WebGestalt, we have generated 48 gene sets with genes over
      represented in various human tissue types. Exploration of all the 48 gene sets
      using WebGestalt is available for the public at
      http://genereg.ornl.gov/webgestalt/wg_enrich.php.

PMID- 15980576
TI  - GenePath: from mutations to genetic networks and back.
AB  - GenePath is a web-based application for the analysis of mutant-based experiments
      and synthesis of genetic networks. Here, we introduce GenePath and describe a
      number of new approaches, including conflict resolution, handling cyclic
      pathways, confidence level assignment, what-if analysis and new experiment
      proposal. We illustrate the key concepts using data from a study of adhesion
      genes in Dictyostelium discoideum and show that GenePath discovered genetic
      interactions that were ignored in the original publication. GenePath is available
      at http://www.genepath.org/genepath2.

PMID- 15980577
TI  - Data mining tools for the Saccharomyces cerevisiae morphological database.
AB  - For comprehensive understanding of precise morphological changes resulting from
      loss-of-function mutagenesis, a large collection of 1,899,247 cell images was
      assembled from 91,71 micrographs of 4782 budding yeast disruptants of non-lethal
      genes. All the cell images were processed computationally to measure
      approximately 500 morphological parameters in individual mutants. We have
      recently made this morphological quantitative data available to the public
      through the Saccharomyces cerevisiae Morphological Database (SCMD). Inspecting
      the significance of morphological discrepancies between the wild type and the
      mutants is expected to provide clues to uncover genes that are relevant to the
      biological processes producing a particular morphology. To facilitate such
      intensive data mining, a suite of new software tools for visualizing parameter
      value distributions was developed to present mutants with significant changes in
      easily understandable forms. In addition, for a given group of mutants associated
      with a particular function, the system automatically identifies a combination of
      multiple morphological parameters that discriminates a mutant group from others
      significantly, thereby characterizing the function effectively. These data mining
      functions are available through the World Wide Web at http://scmd.gi.k.u
      tokyo.ac.jp/.

PMID- 15980578
TI  - GeneSeeker: extraction and integration of human disease-related information from
      web-based genetic databases.
AB  - The identification of genes underlying human genetic disorders requires the
      combination of data related to cytogenetic localization, phenotypes and
      expression patterns, to generate a list of candidate genes. In the field of human
      genetics, it is normal to perform this combination analysis by hand. We report on
      GeneSeeker (http://www.cmbi.ru.nl/GeneSeeker/), a web server that gathers and
      combines data from a series of databases. All database searches are performed via
      the web interfaces provided with the original databases, guaranteeing that the
      most recent data are queried, and obviating data warehousing. GeneSeeker makes
      the same selection of candidate genes as the human geneticists would have
      performed, and thus reducing the time-consuming process to a few minutes.
      GeneSeeker is particularly well suited for syndromes in which the disease gene
      displays altered expression patterns in the affected tissue(s).

PMID- 15980579
TI  - Recent additions and improvements to the Onto-Tools.
AB  - The Onto-Tools suite is composed of an annotation database and six seamlessly
      integrated, web-accessible data mining tools: Onto-Express, Onto-Compare, Onto
      Design, Onto-Translate, Onto-Miner and Pathway-Express. The Onto-Tools database
      has been expanded to include various types of data from 12 new databases. Our
      database now integrates different types of genomic data from 19 sequence, gene,
      protein and annotation databases. Additionally, our database is also expanded to
      include complete Gene Ontology (GO) annotations. Using the enhanced database and
      GO annotations, Onto-Express now allows functional profiling for 24 organisms and
      supports 17 different types of input IDs. Onto-Translate is also enhanced to
      fully utilize the capabilities of the new Onto-Tools database with an ultimate
      goal of providing the users with a non-redundant and complete mapping from any
      type of identification system to any other type. Currently, Onto-Translate allows
      arbitrary mappings between 29 types of IDs. Pathway-Express is a new tool that
      helps the users find the most interesting pathways for their input list of genes.
      Onto-Tools are freely available at http://vortex.cs.wayne.edu/Projects.html.

PMID- 15980580
TI  - MRS: a fast and compact retrieval system for biological data.
AB  - The biological data explosion of the 'omics' era requires fast access to many
      data types in rapidly growing data banks. The MRS server allows for very rapid
      queries in a large number of flat-file data banks, such as EMBL, UniProt, OMIM,
      dbEST, PDB, KEGG, etc. This server combines a fast and reliable backend with a
      very user-friendly implementation of all the commonly used information retrieval
      facilities. The MRS server is freely accessible at http://mrs.cmbi.ru.nl/.
      Moreover, the MRS software is freely available at http://mrs.cmbi.ru.nl/download/
      for those interested in making their own data banks available via a web-based
      server.

PMID- 15980581
TI  - PROTINFO: new algorithms for enhanced protein structure predictions.
AB  - We describe new algorithms and modules for protein structure prediction available
      as part of the PROTINFO web server. The modules, comparative and de novo
      modelling, have significantly improved back-end algorithms that were rigorously
      evaluated at the sixth meeting on the Critical Assessment of Protein Structure
      Prediction methods. We were one of four server groups invited to make an oral
      presentation (only the best performing groups are asked to do so). These two
      modules allow a user to submit a protein sequence and return atomic coordinates
      representing the tertiary structure of that protein. The PROTINFO server is
      available at http://protinfo.compbio.washington.edu.

PMID- 15980582
TI  - Current Comparative Table (CCT) automates customized searches of dynamic
      biological databases.
AB  - The Current Comparative Table (CCT) software program enables working biologists
      to automate customized bioinformatics searches, typically of remote sequence or
      HMM (hidden Markov model) databases. CCT currently supports BLAST, hmmpfam and
      other programs useful for gene and ortholog identification. The software is web
      based, has a BioPerl core and can be used remotely via a browser or locally on
      Mac OS X or Linux machines. CCT is particularly useful to scientists who study
      large sets of molecules in today's evolving information landscape because it
      color-codes all result files by age and highlights even tiny changes in sequence
      or annotation. By empowering non-bioinformaticians to automate custom searches
      and examine current results in context at a glance, CCT allows a remote database
      submission in the evening to influence the next morning's bench experiment. A
      demonstration of CCT is available at http://orb.public.stolaf.edu/CCTdemo and the
      open source software is freely available from http://sourceforge.net/projects/orb
      cct.

PMID- 15980583
TI  - PubFinder: a tool for improving retrieval rate of relevant PubMed abstracts.
AB  - Since it is becoming increasingly laborious to manually extract useful
      information embedded in the ever-growing volumes of literature, automated
      intelligent text analysis tools are becoming more and more essential to assist in
      this task. PubFinder (www.glycosciences.de/tools/PubFinder) is a publicly
      available web tool designed to improve the retrieval rate of scientific abstracts
      relevant for a specific scientific topic. Only the selection of a representative
      set of abstracts is required, which are central for a scientific topic. No
      special knowledge concerning the query-syntax is necessary. Based on the selected
      abstracts, a list of discriminating words is automatically calculated, which is
      subsequently used for scoring all defined PubMed abstracts for their probability
      of belonging to the defined scientific topic. This results in a hit-list of
      references in the descending order of their likelihood score. The algorithms and
      procedures implemented in PubFinder facilitate the perpetual task for every
      scientist of staying up-to-date with current publications dealing with a specific
      subject in biomedicine.

PMID- 15980584
TI  - LitMiner and WikiGene: identifying problem-related key players of gene regulation
      using publication abstracts.
AB  - The LitMiner software is a literature data-mining tool that facilitates the
      identification of major gene regulation key players related to a user-defined
      field of interest in PubMed abstracts. The prediction of gene-regulatory
      relationships is based on co-occurrence analysis of key terms within the
      abstracts. LitMiner predicts relationships between key terms from the biomedical
      domain in four categories (genes, chemical compounds, diseases and tissues).
      Owing to the limitations (no direction, unverified automatic prediction) of the
      co-occurrence approach, the primary data in the LitMiner database represent
      postulated basic gene-gene relationships. The usefulness of the LitMiner system
      has been demonstrated recently in a study that reconstructed disease-related
      regulatory networks by promoter modelling that was initiated by a LitMiner
      generated primary gene list. To overcome the limitations and to verify and
      improve the data, we developed WikiGene, a Wiki-based curation tool that allows
      revision of the data by expert users over the Internet. LitMiner
      (http://andromeda.gsf.de/litminer) and WikiGene (http://andromeda.gsf.de/wiki)
      can be used unrestricted with any Internet browser.

PMID- 15980585
TI  - GoPubMed: exploring PubMed with the Gene Ontology.
AB  - The biomedical literature grows at a tremendous rate and PubMed comprises already
      over 15 000 000 abstracts. Finding relevant literature is an important and
      difficult problem. We introduce GoPubMed, a web server which allows users to
      explore PubMed search results with the Gene Ontology (GO), a hierarchically
      structured vocabulary for molecular biology. GoPubMed provides the following
      benefits: first, it gives an overview of the literature abstracts by categorizing
      abstracts according to the GO and thus allowing users to quickly navigate through
      the abstracts by category. Second, it automatically shows general ontology terms
      related to the original query, which often do not even appear directly in the
      abstract. Third, it enables users to verify its classification because GO terms
      are highlighted in the abstracts and as each term is labelled with an accuracy
      percentage. Fourth, exploring PubMed abstracts with GoPubMed is useful as it
      shows definitions of GO terms without the need for further look up. GoPubMed is
      online at www.gopubmed.org. Querying is currently limited to 100 papers per
      query.

PMID- 15980586
TI  - ProTarget: automatic prediction of protein structure novelty.
AB  - ProTarget is a Web-based tool for the automatic prediction of fold novelty. It
      offers the structural genomics community a method for target selection by
      providing an online analysis of any new or pre-existing sequence for its
      relationship to any previously solved three-dimensional structure. ProTarget
      takes as input an amino acid sequence. Regions of this sequence that exhibit high
      similarity to an existing PDB (Protein Data Bank) sequence are removed, leaving
      one or more subsequences. Each of these subsequences is then analyzed against a
      clustering of the protein space to determine the likelihood of its representing a
      new structural superfamily. This likelihood is derived from the distance in the
      clustering between the (sub)sequence and sequences that have known structures.
      The output of ProTarget is a graphical visualization of the protein of interest
      together with the likelihood that a protein sequence represents a novel
      structural superfamily. ProTarget is updated regularly and currently covers over
      160 000 protein sequences from the SwissProt and PDB databases. ProTarget is
      available at http://www.protarget.cs.huji.ac.il.

PMID- 15980587
TI  - Fragment Finder: a web-based software to identify similar three-dimensional
      structural motif.
AB  - FF (Fragment Finder) is a web-based interactive search engine developed to
      retrieve the user-desired similar 3D structural fragments from the selected
      subset of 25 or 90% non-homologous protein chains. The search is based on the
      comparison of the main chain backbone conformational angles (phi and ).
      Additionally, the queried motifs can be superimposed to find out how similar the
      structural fragments are, so that the information can be effectively used in
      molecular modeling. The engine has facilities to view the resultant superposed or
      individual 3D structure(s) on the client machine. The proposed web server is made
      freely accessible at the following URL: http://cluster.physics.iisc.ernet.in/ff/
      or http://144.16.71.148/ff/.

PMID- 15980588
TI  - ProFunc: a server for predicting protein function from 3D structure.
AB  - ProFunc (http://www.ebi.ac.uk/thornton-srv/databases/ProFunc) is a web server for
      predicting the likely function of proteins whose 3D structure is known but whose
      function is not. Users submit the coordinates of their structure to the server in
      PDB format. ProFunc makes use of both existing and novel methods to analyse the
      protein's sequence and structure identifying functional motifs or close
      relationships to functionally characterized proteins. A summary of the analyses
      provides an at-a-glance view of what each of the different methods has found.
      More detailed results are available on separate pages. Often where one method has
      failed to find anything useful another may be more forthcoming. The server is
      likely to be of most use in structural genomics where a large proportion of the
      proteins whose structures are solved are of hypothetical proteins of unknown
      function. However, it may also find use in a comparative analysis of members of
      large protein families. It provides a convenient compendium of sequence and
      structural information that often hold vital functional clues to be followed up
      experimentally.

PMID- 15980589
TI  - PISCES: recent improvements to a PDB sequence culling server.
AB  - PISCES is a database server for producing lists of sequences from the Protein
      Data Bank (PDB) using a number of entry- and chain-specific criteria and mutual
      sequence identity. Our goal in culling the PDB is to provide the longest list
      possible of the highest resolution structures that fulfill the sequence identity
      and structural quality cut-offs. The new PISCES server uses a combination of PSI
      BLAST and structure-based alignments to determine sequence identities. Structure
      alignment produces more complete alignments and therefore more accurate sequence
      identities than PSI-BLAST. PISCES now allows a user to cull the PDB by-entry in
      addition to the standard culling by individual chains. In this scenario, a list
      will contain only entries that do not have a chain that has a sequence identity
      to any chain in any other entry in the list over the sequence identity cut-off.
      PISCES also provides fully annotated sequences including gene name and species.
      The server allows a user to cull an input list of entries or chains, so that
      other criteria, such as function, can be used. Results from a search on the re
      engineered RCSB's site for the PDB can be entered into the PISCES server by a
      single click, combining the powerful searching abilities of the PDB with PISCES's
      utilities for sequence culling. The server's data are updated weekly. The server
      is available at http://dunbrack.fccc.edu/pisces.

PMID- 15980590
TI  - WebProAnalyst: an interactive tool for analysis of quantitative structure
      activity relationships in protein families.
AB  - WebProAnalyst is a web-accessible analysis tool
      (http://wwwmgs.bionet.nsc.ru/mgs/programs/panalyst/) designed for scanning
      quantitative structure-activity relationships in protein families. The tool
      allows users to search correlations between protein activity and physicochemical
      characteristics (i.e. hydrophobicity or alpha-helical amphipathicity) in queried
      sequences. WebProAnalyst uses aligned amino acid sequences and data on protein
      activity (pK, K(m), ED(50), among others). WebProAnalyst implements methods of
      the known ProAnalyst package, including the multiple linear regression analysis
      and the sequence-activity correlation coefficient. In addition, WebProAnalyst
      incorporates a method based on neural networks. The WebProAnalyst reports a list
      of sites in protein family, the regression analysis parameters (including
      correlation values) for the relationships between the amino acid physicochemical
      characteristics in the site and the protein activity values. WebProAnalyst is
      useful in search of the amino acid residues that are important for protein
      function/activity. Furthermore, WebProAnalyst may be helpful in designing the
      protein-engineering experiments.

PMID- 15980591
TI  - Preparation of aggregate-free, low molecular weight amyloid-beta for assembly and
      toxicity assays.
AB  - More than 20 diseases have been identified which are caused by the deposition of
      amyloid. Natural and chemically synthesized amyloidogenic proteins are used
      widely to study the structure, assembly, and physiologic effects of both
      oligomeric and fibrillar forms of these proteins. In many cases, conflicting
      results arise in these studies, in part owing to difficulties in reproducibly
      preparing amyloidogenic proteins in a well-defined assembly state. To avoid these
      problems, several methods have been devised that provide reliable means of
      preparing amyloid-forming proteins for experimental use. Here, we discuss methods
      that have been used successfully to prepare one such protein, the amyloid beta
      protein (Abeta), involved in Alzheimer's disease. Methods for reproducible
      preparation of Abeta in a well-defined assembly state include isolation of low
      molecular weight (LMW) Abeta by size exclusion chromatography, filtration through
      LMW cut-off filters, and solubilization/lyophilization in the presence of
      reagents which facilitate disassembly of Abeta. These reagents include strong
      bases and acids, and fluorinated alcohols. These methods, which were originally
      developed for Abeta, are generally applicable to amyloidogenic peptides and
      proteins. In this chapter, we describe the preparation of LMW Abeta using size
      exclusion chromatography and filtration. The advantages and disadvantages of each
      method are discussed.

PMID- 15980592
TI  - Determination of Peptide oligomerization state using rapid photochemical
      crosslinking.
AB  - The assembly of the amyloid beta-protein (Abeta) into neurotoxic oligomers and
      fibrils is a seminal pathogenic process in Alzheimer's disease (AD).
      Understanding the mechanisms of Abeta assembly could prove useful in the
      identification of therapeutic targets. Owing to the metastable nature of Abeta
      oligomers, it is difficult to obtain interpretable data through application of
      classical methods, such as electrophoresis, chromatography, fluorescence, and
      light scattering. Here, we apply the method Photo-Induced Crosslinking of
      Unmodified Proteins (PICUP) to the study of Abeta oligomerization. This method
      directly produces covalent bonds among unmodified polypeptide chains through in
      situ generation of peptide free radicals. PICUP provides a snapshot of the native
      oligomerization state of proteins and can be used for assembly state analysis of
      a wide variety of peptides and proteins.

PMID- 15980593
TI  - In vitro preparation of prefibrillar intermediates of amyloid-beta and alpha
      synuclein.
AB  - Elucidating the structural properties of early intermediates (protofibrils) on
      the fibril formation pathway of Abeta and alpha-synuclein, the structural
      relationship among the different intermediates and their relationship to the
      structure of the amyloid fibrils is critical for understanding the roles of
      amyloid fibril formation in the pathogenesis of Alzheimer's and Parkinson's
      diseases. In this chapter we discuss several methods, developed by different
      laboratories, that enable the preparation and stabilization of amyloid-beta and
      alpha-synuclein protofibrillar species of defined morphologies for biochemical,
      biophysical and toxicity studies.

PMID- 15980594
TI  - Purification of recombinant tau protein and preparation of Alzheimer-paired
      helical filaments in vitro.
AB  - The tau protein is a neuronal microtubule-associated protein. Apart of its
      physiological function-the binding to and stabilization of microtubules-tau is
      found in Alzheimer's disease brain as insoluble fibers, the so-called "paired
      helical filaments" (PHFs). Investigating the fundamentals of tau polymerization
      is indispensable for identifying inhibitory conditions or compounds preventing
      PHF formation, which may slow down or even stop the degeneration of neurons in
      Alzheimer's disease. In this chapter, we describe the methods necessary for
      studying the characteristics of tau polymerization to PHFs. These include: a
      purification protocol for recombinantly expressed tau; a general method for the
      polyanion induced polymerization of tau to PHFs; the quantitation of PHFs by a
      fluorescence-based assay; the imaging and verification of PHFs by negative stain
      transmission electron microscopy.

PMID- 15980595
TI  - Cyclic amplification of protein misfolding and aggregation.
AB  - Diverse human disorders, including most neurodegenerative diseases, are thought
      to arise from the misfolding and aggregation of an underlying protein. We have
      recently described a novel technology to amplify cyclically the misfolding and
      aggregation process in vitro. This procedure, named protein misfolding cyclic
      amplification (PMCA), conceptually analogous to DNA amplification by PCR, has
      tremendous implications for research and diagnosis. The PMCA concept has been
      proved on the amplification of prions implicated in the pathogenesis of
      transmissible spongiform encephalopathies (TSE). In these diseases, there is a
      tremendous need for early and sensitive biochemical diagnosis to minimize the
      further spreading of the prion infectious agent through the food chain. In this
      chapter, we describe the principles behind the PMCA technology, its application,
      and methodology to detect minute quantities of misfolded prion protein and its
      potential to be used for amplification of misfolding of other proteins implicated
      in diverse diseases.

PMID- 15980596
TI  - X-ray diffraction studies of amyloid structure.
AB  - Elucidation of the underlying core structure of amyloid fibrils is essential for
      understanding the mechanism by which amyloid fibrils are formed and deposited.
      Conventional methods of X-ray crystallography and NMR cannot be used, since the
      fibers are insoluble and heterogeneous. X-ray fiber diffraction is one method
      that has been successfully used to examine the structure of these insoluble
      fibers. The procedure involves the formation of suitable, ordered amyloid fibrils
      and characterization (by electron microscopy), partial alignment of fibers, X-ray
      data collection, data analysis, and finally, model building.

PMID- 15980597
TI  - Molecular electron microscopy approaches to elucidating the mechanisms of protein
      fibrillogenesis.
AB  - Electron microscopy (EM) has played a central role in our current understanding
      of the mechanisms underlying the pathogenesis of several amyloid diseases,
      including Alzheimer's disease, Parkinson's disease, and prion diseases. In this
      chapter, we discuss the application of various EM techniques to monitor and
      characterize quaternary structural changes during amyloid fibril formation in
      vitro and the potential of extending some of these techniques to characterizing
      ex vivo material. In particular, we would like to bring to the attention of the
      reader two very powerful molecular EM techniques that remain under utilized by
      researchers in the amyloid community, namely scanning transmission electron
      microscopy and single particle molecular averaging EM. An overview of the
      strength and limitations of these techniques as tools for elucidating the
      structural basis of amyloid fibril formation will be presented.

PMID- 15980598
TI  - Time-lapse atomic force microscopy in the characterization of amyloid-like fibril
      assembly and oligomeric intermediates.
AB  - The atomic force microscope (AFM) images the topography of biological structures
      adsorbed to surfaces with nanometer to angstrom scale resolution. Amyloid-like
      fibrils and oligomers can be imaged in buffer solutions, allowing the samples to
      retain physiological-like properties while temporal changes in structure are
      monitored, e.g., the elongation of fibrils or the growth of single oligomers.
      These qualities distinguish AFM from conventional imaging techniques of
      comparable resolution, i.e., electron microscopy (EM). However, AFM is limited in
      that the specimen must be firmly attached to a solid support for measurement and
      that time-lapse imaging of individual assemblies can thus only be achieved for
      fibrils and oligomers growing on this support. Nevertheless, AFM has provided
      several insights into the in vitro assembly mechanism and structures of amyloid
      like fibrils. The first section of this chapter provides a methodological
      introduction to AFM, whilst the second details the application of this technique
      to the investigation of amyloidogenic proteins, specifically amylin and amyloid
      beta (Abeta) peptides.

PMID- 15980599
TI  - Fourier transform infrared and circular dichroism spectroscopies for amyloid
      studies.
AB  - Amyloids, found as extracellular protein deposits in a diverse group of human and
      animal disorders, are characterized by a basic scaffold consisting of cross beta
      sheet structure. Both far-UV circular dichroism and Fourier transform infrared
      spectroscopy (FTIR) spectroscopies are the most commonly used techniques for
      determining the secondary structure of proteins and peptides that either have not
      been or cannot be studied by nuclear magnetic resonance or X-ray crystallography.
      Both techniques are complementary and preferentially used depending on the
      physical state of the analyte and the major secondary structure element. Although
      there are special setups for working with films, circular dichroism is best
      suited for diluted solutions of poly-peptides exhibiting alpha-helix as major
      structural element. On the other hand, FTIR works best with concentrated
      solutions, solids, and films and resolves with accuracy the beta-sheet
      composition. Both spectroscopies need a small amount of protein for analysis, are
      non-destructive and can monitor very accurately relative changes owing to the
      influence of environment of the sample, though display interferences with some
      widely used chemicals. Within the amyloid field, conjunction of both
      spectroscopies has provided the first filter step for amyloid detection and has
      contributed to decipher the structural aspects of the amyloid formation
      mechanism.

PMID- 15980600
TI  - Quasielastic light scattering for protein assembly studies.
AB  - Quasielastic light scattering (QLS) spectroscopy is an optical method for the
      determination of diffusion coefficients of particles in solution. In this
      chapter, we discuss the principles and practice of QLS with respect to protein
      assembly reactions. Particles undergoing Brownian motion produce fluctuations in
      scattered light intensity. We describe how the temporal correlation function of
      these fluctuations can be measured and how this correlation function provides
      information about the distribution of diffusion coefficients of the particles in
      solution. We discuss the intricacies of deconvolution of the correlation function
      and the assumptions incorporated into data analysis procedures. We explain how
      the Stokes-Einstein relationship can be used to convert distributions of
      diffusion coefficients into distributions of particle size. Noninvasive
      observation of the temporal evolution of particles sizes provides a powerful tool
      for studying protein aggregation and self-assembly. We use examples from studies
      of Abeta fibrillogenesis to illustrate QLS application for understanding the
      molecular mechanisms of the nucleation and growth of amyloid fibrils.

PMID- 15980601
TI  - Intrinsic fluorescent detection of tau conformation and aggregation.
AB  - The polymerization of the microtubule-associated protein tau into paired helical
      filaments (PHFs) is one of the hallmarks of Alzheimer's disease. Insights into
      the prerequisites and kinetics of the polymerization was obtained by the in vitro
      analysis of this process. In the past, fluorescent dyes were used to stain
      amyloidogenic material in histology and later on similar dyes were used in in
      vitro studies as well. To circumvent the flaws of extragenous dyes, namely the
      alteration of the polymerization kinetic or incompatibility with other chemical
      compounds needed for stability analysis, we applied tryptophan fluorescence to
      the in vitro analysis of PHF formation. Single tryptophans were introduced into
      the hexapeptide PHF6 within the third repeat, which was shown to be involved in
      beta sheet formation and scattered around the whole microtubule binding domain.
      Tryptophan fluorescence was then used to scan the microtubule binding domain for
      accessibility to quenching reagent in the soluble and the aggregated state and
      the fluorescence resonance energy transfer (FRET) between tryptophan and tyrosine
      310. Furthermore, this approach enables the analysis of stability of PHFs in the
      presence of Guanidinium hydrochloride. The examples given here could be applied
      in modified ways to other amyloidogenic proteins.

PMID- 15980602
TI  - Quantitative measurement of fibrillogenesis by mass spectrometry.
AB  - In this chapter, a method for the quantitative determination of amyloid
      conversion by electrospray mass spectrometry is presented. Mass spectrometry is
      typically used for the purpose of measuring the mass of unknowns. However, the
      judicious selection of an internal standard permits the quantitative
      determination of protein concentration. For amyloid formation, this is
      particularly useful in circumstances where either the protein under study is in
      limited abundance, or separation of the precursor from other protein factors is
      impractical or undesirable. For the measurement of amyloid formation, internal
      standards are typically mass distinct variants of the amyloid precursor. In
      addition, the extreme stability of amyloid fibers permits assessment of residual
      precursor concentration with or without separation of fibers from unreacted
      precursor. Lastly, by using internal standards which are not amyloidogenic and do
      not interfere with fiber formation, electrospray mass spectrometry permits
      quantitative measurement of fiber formation in real-time and with small (pmoles)
      quantities of protein.

PMID- 15980603
TI  - Isolation and culturing of human vascular smooth muscle cells.
AB  - Cerebral amyloid angiopathy (CAA) results from amyloid accumulation within
      arteries of the cerebral cortex and leptomeninges. This condition is age-related,
      especially prevalent in Alz-heimer's disease (AD), and the main feature of
      certain hereditary disorders (i.e., HCHWA-I). The vascular smooth muscle cells
      (VSMCs) appear to play a vital role in the development of CAA, which makes them
      well-suited as an experimental model to study the disease and screen for possible
      remedies. We describe two different methods for isolating and culturing human
      VSMCs. First, using the human umbilical cord as an easy source of robust cells,
      and secondly, using brain tissue that provides the proper cerebral VSMCs, but is
      more problematic to work with. Finally the maintenance, preservation, and
      characterization of the isolated VSMCs are described.

PMID- 15980604
TI  - Murine cerebrovascular cells as a cell culture model for cerebral amyloid
      angiopathy: isolation of smooth muscle and endothelial cells from mouse brain.
AB  - The use of murine cerebrovascular cells, that is, endothelial and smooth muscle
      cells, has not been widely employed as a cell culture model for the investigation
      of cellular mechanisms involved in cerebral amyloid angiopathy (CAA).
      Difficulties in isolation and propagation of murine cerebrovascular cells and
      insufficient yields for molecular and cell culture studies have deterred
      investigators from using mice as a source for cerebrovascular cells in culture.
      To date, most of the literature has described isolation of smooth muscle cells or
      endothelial cells from human, canine, rat, guinea pig, or other large animals. In
      recent years, several transgenic mice have been established that show CAA
      pathology; therefore, it is necessary to re-examine the use of mouse
      cerebrovascular cells as an important model for cell culture studies. We have
      optimized the isolation procedure of (1) murine microvessels, (2) smooth muscle
      cells, and (3) endothelial cells to yield a sufficient population of cells for
      experimentation purposes. Comparisons with rat and human isolation procedures are
      also noted. Murine smooth muscle cells isolated using the methodology described
      herein exhibit the classic "hill and valley" morphology and are immunoreactive
      for smooth muscle cell-specific alpha-actin, whereas endothelial cells
      demonstrate a more "cobblestone" appearance and stain for von Willebrand factor
      or factor VIII-related antigen.

PMID- 15980605
TI  - Purification of human wild-type or variant cystatin C from conditioned media of
      transfected cells.
AB  - The characterization of proteins in their native state is essential for the
      understanding of patho-genic isoforms. A variant of the cysteine protease
      inhibitor cystatin C is the major constituent of the amyloid deposited in the
      cerebral vasculature of patients with the Icelandic form of hereditary cerebral
      hemorrhage with amyloidosis (HCHWA-I). In order to study the nature of the bio
      physical changes owing to the Leu68Gln substitution in cystatin C, we have
      developed a purification procedure of human cystatin C in its native state. The
      protein is isolated from media of stably transfected tissue culture cells using
      physiological conditions that preclude protein denaturation. The importance of
      mild purification conditions is underscored by the finding that denaturation of
      the wild-type and variant proteins facilitates a similar folding of both
      molecules, diminishing their differences in structure and biophysical properties.
      Following native purification conditions, variant cystatin C has a distinct
      structure compared to the wild-type protein.

PMID- 15980606
TI  - Prion propagation in cell culture.
AB  - During the past two decades, considerable efforts have been made to set up
      cellular cultures supporting the replication of prions, the infectious agents
      responsible of transmissible spongiform encephalopathies. As a matter of fact,
      prion-infected cell lines are very valuable to investigate the cell biology of
      both the normal and the pathological isoform of the prion protein or to develop
      and screen new therapeutics. In this chapter, we present a detailed protocol for
      the generation of prion-infected cells. We also give step-by-step procedures to
      test the biochemical properties (mainly protease resistance and insolubility) of
      abnormal PrP molecules, which detection represents a biochemical marker of prion
      propagation.

PMID- 15980607
TI  - Preparation and propagation of amyloid-enhancing factor.
AB  - Amyloid-enhancing factor (AEF) is a biological "activity" that is defined in the
      context of inflammation-associated amyloidogenesis (AA). When administered
      intravenously to mice followed by an inflammatory stimulus, such primed mice
      deposit substantial AA amyloid in spleen within 36-48 h. Since experimental
      induction of AEF is dependent on amyloidogenic protocols, and rapid AA amyloid
      induction is dependent on AEF, a strategy for AEF isolation is required to break
      into this circular process. AEF activity may be prepared from a variety of human
      forms of amyloid that include tissue containing any of Abeta, AA, ATTR, and AL
      amyloids. The preparation of an AEF extract from such human tissue is described
      using 4 M glycerol, which then may be used to induce splenic AA amyloid fibrils
      in mice as a source for the propagation of additional AEF and/or for the study of
      amyloidogenesis. The glycerol and AA fibril preparations are stable frozen for
      many years.

PMID- 15980608
TI  - Purification of amyloid protein AA subspecies from amyloid-rich human tissues.
AB  - Protein AA, the major amyloid fibril protein in reactive (secondary) systemic
      amyloidosis is derived from the acute phase reactant liver-produced
      apolipoprotein serum AA (SAA) by proteolytic cleavage, usually in the C-terminal
      half of the 104 amino acid residues long precursor. The cleavage points in SAA
      vary between patients and the deposited protein AA is often quite heterogeneous.
      In this chapter, we describe methods to extract amyloid fibrils and to purify
      protein AA by sequential gel filtration. Further purification of subspecies of
      protein AA is best achieved by the use of differences in charge and
      chromatofocusing is described as the method of choice. Analytic methods include
      sodium dodecylsulfate polyacrylamide gel electrophoresis and analytic isoelectric
      focusing.

PMID- 15980609
TI  - Purification of transthyretin and transthyretin fragments from amyloid-rich human
      tissues.
AB  - Transthyretin is the major amyloid fibril protein in many forms of familial
      systemic amyloidosis where a missense mutation creates an amyloidogenic protein,
      and in senile systemic amyloidosis in which wild-type transthyretin aggregates
      into amyloid fibrils. The amyloid deposits may consist of full-length
      transthyretin but is very often, in senile systemic amyloidosis always, a mixture
      of full-length transthyretin and C-terminal transthyretin fragments. The amyloid
      fibril protein mixture can be purified by extraction of fibrils followed by
      sequential gel filtration after solubilization in a solution of guanidine
      hydrochloride. Since the C-terminal transthyretin fragments lack cysteine
      residues, a method to separate full-length transthyretin from fragments by
      covalent chromatography has been developed.

PMID- 15980610
TI  - Extraction and chemical characterization of tissue-deposited proteins from minute
      diagnostic biopsy specimens.
AB  - The compelling need for early detection and chemical characterization of protein
      deposits in conformational disorders has always relied on immunohistochemical
      techniques performed on diagnostic biopsy specimens. Although the identity of the
      culprit can be assessed, the molecular nature of the defect still requires the
      analysis of the extracted material. The purpose of this chapter is to provide
      investigators with a method to extract and analyze-from minute residual
      diagnostic tissue biopsies-the deposited proteins. If done successfully, the
      technique will allow further investigation by molecular studies, while the
      patient is still being evaluated.

PMID- 15980611
TI  - Tissue processing prior to protein analysis and amyloid-beta quantitation.
AB  - Amyloid-containing tissue, whether from human patients or an animal model of a
      disease, is typically characterized by various biochemical and
      immunohistochemical techniques, many of which are described in detail in this
      volume. In this chapter, we describe a straightforward technique for the
      homogenization of tissue prior to these analyses. The technique is particularly
      well-suited for performing a large number of different biochemical analyses on a
      single mouse brain hemisphere. Starting with this homogenate, multiple
      characterizations can be done, including Western blot analysis and isolation of
      membrane-associated proteins, both of which are described here. Additional
      analyses can readily be performed on the tissue homogenate, including the ELISA
      quantitation of Abeta in the brain of a transgenic mouse model of beta-amyloid
      deposition. The ELISA technique is described in detail in the following chapter.

PMID- 15980612
TI  - ELISA method for measurement of amyloid-beta levels.
AB  - The neuritic plaque in the brain of Alzheimer's disease (AD) patients consists of
      an amyloid composed primarily of Abeta, an approx 4-kDa peptide derived from the
      amyloid precursor protein. Multiple lines of evidence suggest that Abeta plays a
      key role in the pathogenesis of the disease, and potential treatments that target
      Abeta production and/or Abeta accumulation in the brain as beta-amyloid are being
      aggressively pursued. Methods to quantitate the Abeta peptide are, therefore,
      invaluable to most studies aimed at a better understanding of the molecular
      etiology of the disease and in assessing potential therapeutics. Although other
      techniques have been used to measure Abeta in the brains of AD patients and beta
      amyloid-depositing transgenic mice, the enzyme-linked immunosorbent assay (ELISA)
      is one of the most commonly used, reliable, and sensitive methods for
      quantitating the Abeta peptide. Here we describe methods for the recovery of both
      soluble and deposited Abeta from brain tissue and the subsequent quantitation of
      the peptide by sandwich ELISA.

PMID- 15980613
TI  - Histological staining of amyloid-beta in mouse brains.
AB  - The increased availability of transgenic mouse models for studying human diseases
      is shifting the focus of many laboratories from in vitro to in vivo assays. The
      purpose of this chapter is to provide investigators with methods that will allow
      them to obtain well-preserved mouse brain sections to be stained with the
      standard histological dyes for amyloid, Congo red and thio-flavin-S. These
      sections can as well be used for immunohistological procedures that allow
      detection of amyloid-beta plaques as well as pre-amyloid deposits.

PMID- 15980614
TI  - The mouse model for scrapie: inoculation, clinical scoring, and histopathological
      techniques.
AB  - The mouse is a popular and versatile model for the study of scrapie and other
      transmissible spongiform encephalopathies. In this chapter, information is given
      for preparation of infectious material for inoculation and a method of clinical
      scoring that yields accurate and reproducible quantification of the scrapie
      incubation period. With the help of histopathological and immunopathological
      techniques, we can detect brain pathological changes in scrapie-infected animals
      at the cellular and molecular level. We will also describe the histological and
      immunocytochemistry methods we use for scrapie research, outline step-by-step
      procedures, discuss tissue preparation, fixation, and processing of specimens,
      and provide special hints to achieve successful staining. We also include our
      results of PrPSc and GFAP immunostaining in scrapie research. In conclusion,
      immunopathological staining is an important and useful tool in the research of
      scrapie pathology.

PMID- 15980615
TI  - Radiolabeling of amyloid-beta peptides.
AB  - Nowadays, a wide variety of protocols for labeling proteins is available.
      However, radiolabeling remains one of the most powerful, sensitive and accurate
      methods to trace and quantitate proteins. Additionally, radiolabeling techniques
      are steadily gaining importance for diagnosis and treatment in nuclear medicine.
      There is a considerable number of radioisotopes, but only some are commonly used
      for basic biomedical research. Among them, the iodine radioisotopes (gamma
      emitters) have several advantages for the labeling of proteins. This chapter
      focuses on radioiodination protocols for amyloidogenic peptides, using the Abeta
      peptides as a paradigm. The chloramine T, Iodo-Gen, and lactoperoxidase methods
      can be successfully applied to radioiodination of different amyloid peptides as
      long as free tyrosyl (or histidyl) groups are avail-able. However, these methods
      differ in their yield and the degree of oxidative damage conferred to labile
      peptides. When no tyrosines are available, the Bolton-Hunter methodology can be
      used. The labeling by the tyramine-cellobiose ligand trapping method is
      applicable to the study of cellular uptake and catabolism of amyloid peptides.

PMID- 15980616
TI  - In vivo imaging of amyloid-beta deposits in mouse brain with multiphoton
      microscopy.
AB  - With the advent of transgenic mouse models expressing cortical amyloid pathology,
      the potential to study its progression in an intact brain has been realized.
      Multiphoton microscopy provides a non-destructive means of imaging with micron
      resolution up to 500 microm deep into the cortex. We detail a surgical procedure
      and discuss a multiphoton imaging approach that allows for labeling and chronic
      visualization of amyloid-beta deposits through a cranial window. The ability to
      monitor these hallmarks of Alzheimer's disease enables studies aimed at
      evaluating the efficacy of treatment and prevention strategies.

PMID- 15980617
TI  - Magnetic resonance imaging of amyloid plaques in transgenic mice.
AB  - Transgenic mice are used increasingly to model brain amyloidosis, mimicking the
      pathogenic processes involved in Alzheimer's disease (AD). In this chapter, a
      strategy is described that has been successfully used to map amyloid deposits in
      transgenic mouse models of AD with magnetic resonance imaging (MRI), utilizing
      molecular targeting vectors labeled with MRI contrast agents to enhance
      selectively the signal from amyloid plaques. To obtain sufficient spatial
      resolution for effective and sensitive mouse brain imaging, magnetic fields of 7
      Tesla (T) or more are required. These are higher than the 1.5-T field strength
      routinely used for human brain imaging. The higher magnetic fields affect
      contrast agent efficiency, and determine the choice of pulse sequence parameters
      for in vivo MRI, all addressed in this chapter. Ex vivo imaging is also described
      as an important step to test and optimize protocols prior to in vivo studies. The
      experimental setup required for mouse brain imaging is explained in detail,
      including anesthesia, immobilization of the mouse head to reduce motion
      artifacts, and anatomical landmarks to use for the slice alignment procedure to
      improve image co-registration during longitudinal studies, and for subsequent
      matching of MRI with histology.

PMID- 15980618
TI  - FHD: an index to evaluate drug elimination by hemodialysis.
AB  - BACKGROUND: In hemodialyzed patients, physicians have to (1) adjust drug dosage
      for a creatinine clearance lower than 10-15 ml/min and (2) know whether or not
      the drug will be removed by the dialysis session to decide whether it may be
      administered before or after the session on dialysis days. However, of several
      indices being used to evaluate drug removal by dialysis none is appropriate and
      we suggest a novel index named F(HD), which reflects the role of hemodialysis
      clearance of a drug in its overall clearance during the session. METHODS:
      Pharmacokinetic simulations were performed to test the influence of dialysis on
      the pharmacokinetics of some drugs, whether F(HD) was considered or not, to
      determine when to administer the drug. F(HD) was then calculated for several
      drugs and its value compared with other indices. Five hemodialysis patients from
      our department for whom the time of drug administration was determined according
      to F(HD) were included in a small study and their drugs' trough concentrations
      were monitored. RESULTS: F(HD) emphasized that considering hemodialysis clearance
      alone may lead to false interpretations of the potential dialyzability of some
      drugs. In our patients, who received their treatment according to the 'F(HD)
      rule', monitoring of trough levels gave satisfactory results. CONCLUSION: The use
      of the 'F(HD) rule' should be tested on a long-term administration basis to
      confirm our conclusion. F(HD )could be the index of choice to determine when to
      administer a drug, before or after the session, in hemodialysis patients.

PMID- 15980619
TI  - The Prometheus device for extracorporeal support of combined liver and renal
      failure.
AB  - BACKGROUND/AIMS: Prometheus is a newly developed extracorporeal liver support
      system that combines removal of albumin-bound substances (adsorption on resin
      adsorbers) and water-soluble substances (diffusion during high-flux
      hemodialysis). Therefore, it is a promising treatment option for patients with
      hepatorenal syndrome (HRS). METHODS: We studied 10 patients with HRS in a
      prospective clinical study. All patients underwent 2 consecutive Prometheus
      treatments. A variety of clinical and biochemical parameters were assessed.
      RESULTS: Prometheus treatment was uncomplicated and safe. A statistically
      significant improvement of serum creatinine and urea concentrations as well as
      blood pH was observed after Prometheus treatment. Furthermore, liver
      detoxification was supported by a significant decrease of serum levels of
      conjugated bilirubin, bile acids and ammonia. CONCLUSIONS: Prometheus is a safe
      treatment for patients with HRS. Both, albumin-bound and water-soluble substances
      were effectively removed. Controlled studies will evaluate the effect of this new
      treatment option on survival in patients with HRS.

PMID- 15980620
TI  - Benefit of glucose-free dialysis solutions on glucose and lipid metabolism in
      peritoneal dialysis patients.
AB  - BACKGROUND: Glucose absorbed from conventional peritoneal dialysis (PD) solutions
      contributes to unfavorable metabolic effects. Its replacement with a glucose-free
      osmotic agent such as icodextrin (ID) or amino acids (AA) may have some benefit
      on glucose and lipid metabolism. METHODS: Serum lipids, insulin sensitivity and
      substrate oxidation (calorimetry) were measured before and after 8 weeks use of
      ID or AA in 22 patients. Calorimetry and blood tests (HbA1c, lipids) were also
      performed after 8 weeks of simultaneous use of ID and AA in 8 patients. RESULTS:
      Cholesterol declined during the use of AA (4.8 +/- 0.3-4.5 +/- 0.3 mmol/l, p =
      0.045). Triglycerides decreased during the use of both ID (2.2 +/- 0.2-1.9 +/-
      0.1 mmol/l, p = 0.019) and AA (1.9 +/- 0.2-1.6 +/- 0.1 mmol/l, p = 0.024). Free
      fatty acids declined during the use of AA. There were no significant changes in
      insulin sensitivity. Glucose oxidation decreased and lipid oxidation increased
      during the use of ID, the changes in substrate oxidation were accentuated during
      the simultaneous use of ID and AA. CONCLUSION: Replacement of glucose with ID or
      AA had a benefit on glucose and lipid metabolism.

PMID- 15980621
TI  - Ultrapure dialysate reduces plasma levels of beta2-microglobulin and pentosidine
      in hemodialysis patients.
AB  - BACKGROUND: beta2-Microglobulin (beta2MG) and carbonyl stress are reported to
      contribute to the development of dialysis-related amyloidosis. The aim of this
      study was to determine whether the purity of dialysate affects plasma levels of
      beta2MG and pentosidine (a surrogate marker of carbonyl stress) in hemodialysis
      patients. METHODS: Sixteen patients on hemodialysis with a polysulfone membrane
      participated in this study. We switched the dialysate from conventional dialysate
      (endotoxin level 0.055-0.066 endotoxin units (EU)/ml) to ultrapure dialysate
      (endotoxin level <0.001 EU/ml), followed patients for 6 months, and then switched
      back to conventional dialysate once again. Plasma levels of beta2MG, pentosidine,
      CRP and interleukin-6 (IL-6) were determined before the switch to ultrapure
      dialysate, 1 and 6 months after the switch to ultrapure dialysate, and 1 month
      after the switch back to conventional dialysate. RESULTS: The switch from
      conventional to ultrapure dialysate significantly decreased plasma levels of
      beta2MG, from 30.1 +/- 1.4 to 27.1 +/- 1.4 mg/dl (p < 0.05) and pentosidine, from
      1,535.8 +/- 107.5 to 1,267.6 +/- 102.9 nmol/l (p < 0.01) after 1 month of use.
      The change of dialysate also significantly decreased plasma levels of CRP, from
      0.28 +/- 0.09 to 0.14 +/- 0.05 mg/dl (p < 0.05) and IL-6, from 9.4 +/- 2.7 to 3.5
      +/- 0.8 pg/ml (p < 0.01) over the 1-month period. These changes in plasma levels
      of beta2MG, pentosidine, CRP and IL-6 were maintained over 6 months after
      switching to ultrapure dialysate and returned to basal levels by switching back
      to a conventional dialysate. CONCLUSIONS: Ultrapure dialysate decreases plasma
      levels of beta2MG, pentosidine and inflammatory markers in hemodialysis patients.
      The use of ultrapure dialysate might be useful in preventing and/or treating
      complications of dialysis, such as dialysis-related amyloidosis, atherosclerosis
      and malnutrition.

PMID- 15980622
TI  - Non-stenotic ruptured atherosclerotic plaque causing thrombo-embolic stroke.

PMID- 15980623
TI  - 3D-rotational angiographic demonstration of dissection of the anterior cerebral
      artery.

PMID- 15980624
TI  - C2 segmental type of vertebral artery with recurrent embolic strokes.

PMID- 15980625
TI  - Repeated vertebral artery dissections--an autopsy case report.

PMID- 15980626
TI  - Wegener's granulomatosis and vertebro-basilar thrombosis.

PMID- 15980627
TI  - Importance of adequate initial antimicrobial therapy.
AB  - BACKGROUND: It has become an article of faith that appropriate antibiotic therapy
      is needed for best outcomes during a serious infection. Despite this long-held
      view, there is some debate about the role of appropriate outcome in serious
      infections, in particular with nosocomial pneumonia. Therefore, more recent data
      on adequacy of antibiotic therapy and outcomes were reviewed. METHODS: The
      medical literature from 1997 to 2004 was surveyed for articles that directly
      dealt with appropriate therapy. Search terms included 'appropriate and
      inappropriate antibiotic therapy', 'adequate antibiotic therapy', 'resistance and
      antibiotic failures' and 'delayed therapy'. The data were abstracted to obtain
      their essential findings. RESULTS: In bacteremia, data are most persuasive that
      appropriate and timely therapy significantly influences outcomes. Areas where
      this may not be the case are studies where coagulase-negative staphylococci are
      isolated in large numbers or in studies where the incidence of appropriate
      therapy is high. One area where data are not conclusive concerns the treatment of
      enteric bacteria carrying extended spectrum betalactamases, where the only
      cephalosporin of concern is ceftazidime. There is not enough data to compare
      carbapenems with specific cephalosporins to conclude that these are the most
      appropriate agents. The studies in regard to nosocomial pneumonias are not as
      conclusive as those with bacteremias. There appears to be a subset of patients
      that do not respond to therapy or do not survive, which confounds studies of this
      population; however, most studies favor a role of appropriate therapy.
      CONCLUSIONS: Appropriate antibiotic therapy has several dimensions. It improves
      outcomes in most serious diseases. Timing of administration and appropriateness,
      based on susceptibility, are the most important determinants, but dosing
      intervals and dose probably play similarly important roles in outcomes that have
      not been examined exhaustively in humans. Other aspects of appropriate therapy
      that deserve attention include a shift to more 'resistance'-proof antibiotics in
      empiric therapy, which may be accompanied by better outcomes.

PMID- 15980628
TI  - In vitro activity of telithromycin against respiratory tract pathogens in
      comparison with other antimicrobial agents.
AB  - This study was done to evaluate the in vitro activity of a new ketolide
      telithromycin in comparison with clarithromycin, erythromycin, moxifloxacin and
      levofloxacin against Streptococcus pneumoniae (n = 67), Haemophilus influenzae (n
      = 139), and Moraxella catarrhalis (n = 46)collected between January and June 2003
      in Hong Kong. Among the H. influenzae isolates, 25.2% produced beta-lactamase,
      while 97.8% of M. catarrhalis isolates produced beta-lactamase. Half of the S.
      pneumoniae isolates were nonsusceptible to penicillin, and 90.9% of these strains
      were resistant to clarithromycin and erythromycin. One (1.5%) S. pneumoniae
      strain was resistant to levofloxacin (MIC = 8 mg/l) and all isolates were
      sensitive to moxifloxacin and telithromycin with MIC <1 mg/l. H. influenzae
      isolates were sensitive to all fluoroquinolones tested and 2.2% of H. influenzae
      were resistant to clarithromycin. M. catarrhalis isolates were sensitive except 1
      strain which was resistant to levofloxacin (MIC = 4 mg/l) and moxifloxacin (8
      mg/l). All M. catarrhalis strains were sensitive to telithromycin with MIC90 =
      0.5 mg/l. Telithromycin demonstrated high activity and no resistance was found in
      all these major respiratory tract pathogens.

PMID- 15980629
TI  - Efficacy of telithromycin in community-acquired pneumonia caused by pneumococci
      with reduced susceptibility to penicillin and/or erythromycin.
AB  - BACKGROUND: The efficacy of oral telithromycin was assessed in patients with
      community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae with
      reduced susceptibility to penicillin and/or erythromycin. METHODS: Patients with
      CAP who had received telithromycin 800 mg once daily for 5 or 7-10 days (n =
      2,289) in eight phase III clinical trials, or telithromycin 800 mg once daily for
      7 days (n = 50) in a phase II study were included in this pooled analysis.
      Patients with S. pneumoniae as the cause of infection were identified, with
      particular focus on those infected with strains with reduced susceptibility to
      penicillin (intermediate, minimal inhibitory concentration (MIC) 0.12-1.0 mg/l;
      resistant, MIC >or=2.0 mg/l) and/or resistance to erythromycin (MIC >or=1.0
      mg/l). Per-protocol clinical and bacteriological outcomes were assessed 7-14 days
      post-therapy in the phase III studies, and at 7-21 days post-therapy or at the
      end of therapy in the phase II study. RESULTS: Of the 327 telithromycin-treated
      patients with S. pneumoniae infection, 61 (19%) were infected with strains with
      reduced susceptibility to penicillin and/or erythromycin. Clinical cure and
      bacterial eradication rates in these patients were 91.8% (56/61) and 93.4%
      (57/61), respectively. Corresponding clinical cure and bacterial eradication
      rates overall for all isolates of pneumococci were 94.5% (309/327) and 96.0%
      (314/327), respectively. All isolates with reduced susceptibility to penicillin
      and/or erythromycin were susceptible to telithromycin (MIC <or=1.0 mg/l).
      CONCLUSION: These results indicate that telithromycin is an effective oral
      antibacterial for the treatment of CAP caused by pneumococci with reduced
      susceptibility to penicillin and/or erythromycin.

PMID- 15980630
TI  - No genetic association between ATP binding cassette proteins and Japanese
      sporadic Alzheimer's disease.
AB  - The identification of the epsilon4 variant of apolipoprotein E as a genetic risk
      factor for late-onset Alzheimer's disease (AD) suggests that cholesterol may play
      a direct role in the pathogenesis of the disease. Recent studies have suggested
      that the ATP-binding cassette (ABC) protein G5 (ABCG5) may be involved in the
      regulation of intestinal cholesterol absorption. Furthermore, genetic variation
      of this locus may affect blood cholesterol concentrations. We therefore studied
      whether the ABCG5 C1950G (Gln640Glu) polymorphism affects the risk of AD. In
      addition, there was no difference in mean baseline cholesterol concentrations
      between individuals with the C/C genotype and carriers of the G allele. Recent
      studies have shown that genetic regions including the ABCA12 gene might also be
      associated with the risk of AD. The ABCA12 gene, located <1 Mb from the peak
      marker on chromosome 2q34, is also a member of the ABC transporter superfamily.
      In the current study, two common polymorphisms of the ABCA12 gene, rs952718 (T/G)
      and rs956133 (A/G), were analyzed in our subjects. These polymorphisms showed no
      association with the risk of AD. Furthermore, we observed weak linkage
      disequilibrium between these two single nucleotide polymorphisms. These results
      indicate that the common polymorphisms of the ABCG5 and ABCA12 genes investigated
      here are not associated with AD.

PMID- 15980631
TI  - Acquired sociopathy and frontotemporal dementia.
AB  - BACKGROUND: It is not understood why some patients with frontotemporal dementia
      (FTD) manifest sociopathic behavior. OBJECTIVE: To examine the prevalence and
      characteristics of sociopathic behavior in FTD patients as compared to those with
      Alzheimer's disease (AD). METHODS AND PARTICIPANTS: We surveyed a group of FTD
      patients and a group of AD patients for sociopathic behavior, evaluated the
      characteristics surrounding their acts, and compared the groups on
      neuropsychological tests and functional neuroimaging. Twenty-eight outpatients
      with FTD (15 men, 13 women; 61.9+/-7.1 years; Mini-Mental State Examination score
      23.6+/-8.1) were compared with 28 patients with clinically probable AD (13 men,
      15 women; 66.1+/-9.2 years; Mini-Mental State Examination score 21.3 +/- 5.3).
      Main outcome measures included: (a) the prevalence of sociopathic acts; (b) a
      structured interview; (c) neuropsychological tests including the Frontal
      Assessment Battery, and (d) clinically obtained positron emission tomography or
      single photon emission tomography scans. RESULTS: Sixteen (57%) of the FTD
      patients had sociopathic behavior compared to two (7%) of the AD patients
      (chi(2)=13.84, p<0.001). Sociopathic acts among FTD patients included unsolicited
      sexual acts, traffic violations, physical assaults, and other unacceptable
      behaviors. On interview, the FTD patients with sociopathic acts were aware of
      their behavior and knew that it was wrong but could not prevent themselves from
      acting impulsively. They claimed subsequent remorse, but they did not act on it
      or show concern for the consequences. Among FTD patients with sociopathy,
      neuropsychological assessment showed impaired motor inhibition, and functional
      neuroimaging showed right frontotemporal involvement. CONCLUSION: The results
      suggest that sociopathy in FTD results from a combination of diminished emotional
      concern for the consequences of their acts and disinhibition consequent to right
      frontotemporal dysfunction. In many jurisdictions, FTD patients with sociopathy
      would not pass legal criteria for 'not guilty by reason of insanity'.

PMID- 15980632
TI  - Fetal gallstones.
AB  - The significance and natural history of fetal cholelithiasis is not yet well
      defined. We report two cases of echogenic foci detected prenatally by ultrasound.
      The gallstones resolved in both cases by 16 weeks following birth. Both infants
      were treated by ursodeoxycholic acid.

PMID- 15980633
TI  - Perinatal outcomes of twin pregnancies discordant for major fetal anomalies.
AB  - OBJECTIVE: The aim of this study was to determine perinatal outcomes of twin
      pregnancies discordant for a major fetal anomaly and to compare with twins
      without anomaly. METHODS: All twin pregnancies admitted or referred to the
      maternal-fetal unit were prospectively entered into a computer database.
      Chorionicity, fetal anomaly, mean gestational age at delivery, birth weight and
      perinatal survival rate were reviewed. MAIN OUTCOME MEASURES: Mean gestational
      age at delivery, birth weight and perinatal survival rate of twins with and
      without anomaly. RESULTS: There were 48 cases of monochorionic diamniotic (MCDA),
      2 cases of monochorionic monoamniotic (MCMA) and 217 twins with dichorionic (DC)
      placentation. Out of 267 twin pregnancies, there were 17 (6.3%) twins with fetal
      anomaly. Twins discordant for a major fetal anomaly were diagnosed in 13 cases
      (4.8%). We observed 3 cases with MCDA and 10 cases with DC placentation and the
      incidence of discordance for a major fetal anomaly as 4.6% (10/217) in DC and
      6.0% (3/50) in MC twin pregnancies. We identified 8 cases (62%) with
      craniospinal, 2 (15%) with gastrointestinal, 2 (15%) with urinary system, and 1
      case (8%) with both craniospinal and gastrointestinal anomalies. There were
      significant differences between the normal co-twin of the major anomaly group (n
      = 13) and twins without anomaly group (n = 235) in mean gestational age at
      delivery (32 vs. 34 weeks; p = 0.029), mean birth weight (1,640 vs. 2,030 g; p =
      0.022) and perinatal survival rate (69.2 vs. 91.1%; p = 0.018), respectively.
      CONCLUSION: The presence of a fetus with a major anomaly in a twin gestation
      increases the risk of preterm delivery, low birth weight and perinatal mortality
      of the normal co-twin.

PMID- 15980634
TI  - Expression of hepatocyte growth factor/scatter factor receptor in IUGR fetuses'
      placentas: an immunohistochemical analysis.
AB  - OBJECTIVE: We aimed to evaluate the expression sta tus of c-met, receptor for the
      hepatocyte growth factor (HGF), in the placentas of intrauterine growth
      retardation (IUGR) fetuses. MATERIALS AND METHODS: Placentas were obtained during
      delivery from both third trimester normal and IUGR complicated pregnancies.
      Ultrasonographic estimation of fetal birth weight has been done and placentas of
      those under the fifth percentile for their gestational ages were enrolled in the
      study group. Eighteen fetuses with IUGR and 6 uncomplicated pregnancies were
      subjected to the study. Histological sections from placentas were
      immunohistochemically evaluated for the expression status of c-met. RESULTS:
      Seventeen of the eighteen patients (94.4%) in the study group were found to have
      overexpression of the c-met while this figure was only 16.7% (1/6) in the control
      group (p < 0.0001). There was a strong statistically significant difference
      between the two groups regarding degree of c-met expression. CONCLUSION: Our
      present findings suggest that c-met is an important cell membrane receptor in
      human placenta. Deregulation of the interaction between HGF and its receptor c
      met during placentation may be the cause responsible for the growth retardation
      of the fetus due to the impaired placental functions.

PMID- 15980635
TI  - Non-invasive management of fetal goiter during maternal treatment of
      hyperthyroidism in Grave's disease.
AB  - There is an increased risk of fetal goiter in patients who have a history of
      Grave's disease and undergo propylthiouracil (PTU) treatment during pregnancy. In
      this report, we describe a case of a fetal goiter detected by antenatal
      ultrasound at the 26th week of gestation in a mother treated with PTU for Grave's
      disease. A 32 x 38 x 20 mm fetal goiter was detected, each lobe measured 30 x 18
      x 18 mm and estimated volume was 10 cm3. Subsequently, fetal thyroid function was
      assessed by umbilical fetal blood sampling. Cord blood showed elevated serum TSH
      (40.2 mU/l) and normal concentrations of free T4 (9.5 pmol/l) and free T3 (2.6
      pmol/l). There were no other ultrasonographic signs of fetal hypothyroidism.
      Based on the above findings, the mother's PTU dosage was reduced to 50 mg daily
      from a total of 150 mg and weekly ultrasonographic examinations were performed.
      Six weeks after the initial ultrasound, a complete regression of the fetal goiter
      was noted. At the 34th week of gestation, the patient was delivered due to
      intrauterine growth restriction and oligohydramnios and gave birth to a male,
      weighing 1,920 g. The newborn thyroid was not palpable and thyroid
      ultrasonography was normal. Cord blood TSH was normal (8.4 mU/l) and free T4 was
      within lower normal limit (9.03 pmol/l). Ten days later, newborn thyroid function
      was normal and the baby did well afterwards. In conclusion, after the evaluation
      of fetal thyroid status, selected cases with fetal goiter can be initially
      managed without intrauterine treatment.

PMID- 15980636
TI  - Prenatal diagnosis of diastematomyelia in a 15-week-old fetus.
AB  - OBJECTIVE: A case of prenatal diagnosis of diastematomyelia is presented.
      METHODS: A case of fetal diastematomyelia, diagnosed by prenatal sonography,
      demonstrated the typical sonographic features of this condition. In this case it
      was detected at 15 weeks of gestation, and presented with a midline echogenic
      focus in the posterior region of the thoracolumbar spine. RESULTS: The pregnancy
      was terminated by induction of labor. The fetus was female and there was a 1-cm
      long endurated hyperemic lesion at the back of the fetus. We confirmed the
      diagnosis of diastematomyelia after termination of pregnancy by plain chest and
      abdominal X-ray and also MRI scanning. CONCLUSION: Isolated diastematomyelia is a
      rare form of spinal dysraphism characterized by a sagittal cleft in the spinal
      cord, conus medullaris and/or filum terminale with splaying of the posterior
      vertebral elements. Prenatal diagnosis of this anomaly is possible in the early
      mid-trimester by sonography, thus allowing for early surgical intervention and a
      favorable prognosis.

PMID- 15980637
TI  - Fetal extradural hematoma: prenatal diagnosis and postmortem examination.
AB  - We report the 1st confirmed case of an extradural hematoma diagnosed in utero by
      ultrasonography and magnetic resonance imaging at 31 weeks' gestation. No signs
      of intracranial hemorrhage were found. During pregnancy, the expecting mother
      suffered from sustained cough, and a blood sample test revealed acute pertussis.
      The presence of fetal hydrocephaly, brain parenchymal deviation, and other
      abnormalities suggested a poor outcome, and based on these findings pregnancy
      termination was recommended and carried out. Postmortem examination confirmed the
      diagnosis of an extradural hematoma in the posterior fossa.

PMID- 15980638
TI  - Combined prenatal ultrasound and magnetic resonance imaging in an extensive
      congenital fibrosarcoma: a case report and review of the literature.
AB  - OBJECTIVE: Tumors of congenital origin differ in their symptoms and signs,
      predominant location and prognosis from those occurred later in childhood. To
      determine whether the prognosis of congenital (infantile) fibrosarcoma in the
      retroperitoneum, an extremely rare form of soft tissue malignant tumor, can be
      assessed prenatally. METHODS: We describe a case of this condition diagnosed in
      utero, including the assessment of the tumor behavior by ultrasound and magnetic
      resonance imaging. We also review the English language literature in Medline over
      the past 10 years and describe the management options available in such cases.
      RESULTS: Our case had precise prenatal findings revealed unfavorable conditions
      such as bulky tumor mass, spinal metastasis and pulmonary hypoplasia. CONCLUSION:
      Fetal imaging studies could accurately identify the invasion of tumor. The
      outcome is usually poor, especially for those fetuses affected by an axial
      location of the tumor.

PMID- 15980639
TI  - Intrauterine fetal resuscitation following complications of closed fetal surgery.
AB  - BACKGROUND: With advances in prenatal diagnosis and surgical technique more fetal
      interventions are being performed. There are limited data about the etiology,
      incidence, management, or long-term outcomes of complications associated with
      these procedures. CASE: A gravida had a fetus diagnosed with posterior urethral
      valve syndrome. During placement of a peritoneal-amniotic shunt, profound fetal
      bradycardia was noted. Using closed fetal surgical techniques successful
      resuscitation was accomplished. CONCLUSION: Closed fetal surgical interventions
      carry the potential for significant complications of varying etiologies.
      Resuscitation can be accomplished. Preparation for potential complications may
      improve outcome.

PMID- 15980640
TI  - Non-invasive fetal RHD exon 7 and exon 10 genotyping using real-time PCR testing
      of fetal DNA in maternal plasma.
AB  - OBJECTIVE: In this prospective study, we assessed the feasibility of foetal RHD
      genotyping by analysis of DNA extracted from plasma samples of Rhesus (Rh) D
      negative pregnant women using real-time PCR and primers and probes targeted
      toward exon 7 and 10 of RHD gene. METHODS: We analysed 24 RhD-negative pregnant
      woman and 4 patients with weak D phenotypes at a gestational age ranging from
      11th to 38th week of gestation and correlated the results with serological
      analysis of cord blood after the delivery. RESULTS: Non-invasive prenatal foetal
      RHD exon 7 genotyping analyses of maternal plasma samples was in complete
      concordance with the serological analysis of cord blood in all 24 RhD-negative
      pregnant women delivering 12 RhD-positive and 12 RhD-negative newborns. RHD exon
      10-specific PCR amplicons were not detected in 2 out of 12 studied plasma samples
      from women bearing RhD-positive foetus, despite the positive amplification in RHD
      exon 7 region observed in all cases. In 1 case red cell serology of cord blood
      revealed that the mother had D-C-E-c+e+ C(w)- and the infant D+C-E-c+e+ C(w)+
      phenotypes. RhD exon 10 real-time PCR analysis of cord blood was also negative.
      These findings may reflect that DC(w)- paternally inherited haplotype probably
      possesses no RHD exon 10. In another case no cord blood sample has been available
      for additional studies. The specificity of both RHD exon 7 and 10 systems
      approached 100% since no RhD-positive signals were detected in women currently
      pregnant with RhD-negative foetus (n = 8). Using real-time PCR and DNA isolated
      from maternal plasma, we easily differentiated pregnant woman whose RBCs had a
      weak D phenotype (n = 4) from truly RhD-negative patients since the threshold
      cycle (C(T)) for RHD exon 10 or 7 amplicons reached nearly the same value like
      C(T) for control beta-globin gene amplicons detecting the total DNA present in
      maternal plasma. However in these cases foetal RhD status cannot be determined.
      CONCLUSION: Prediction offoetal RhD status from maternal plasma is highly
      accurate and enables implementation into clinical routine. We suggest that safe
      non-invasive prenatal foetal RHD genotyping using maternal plasma should involve
      the amplification of at least two RHD-specific products.

PMID- 15980641
TI  - Mild cerebral ventriculomegaly in fetuses: characteristics and outcome.
AB  - BACKGROUND: A fetal ultrasonographic (US) finding of mild ventriculomegaly (MVM)
      is not uncommon, but its prognostic significance is not clearly defined.
      OBJECTIVE: To evaluate the clinical and US characteristics and outcome of fetuses
      with mild dilatation of the cerebral lateral ventricles. PATIENTS AND METHODS: We
      reviewed the medical records of 34 consecutive fetuses with US evidence of MVM
      (atrial width of the lateral ventricles = 10-15 mm) at 18-35 weeks of gestation.
      RESULTS: Of the 34 fetuses with MVM, 7 underwent karyotype examination and were
      normal. In 4 of the 34 fetuses the pregnancy was terminated (at autopsy: 1 was
      normal, 2 had hydrocephalus and for 1 the parents refused autopsy). Eight fetuses
      that were delivered had congenital malformations; 3 of them died during the early
      neonatal period. In 6 of the 8 fetuses with malformations, karyotypes were
      available and 3 had chromosomal aberrations (trisomy 18, 45XO, and triploidy
      69XXX). Spontaneous in utero resolution of the MVM occurred in 10/30 (33.3%) of
      the cases. Of the 26 infants that remained in follow-up, 16 (61.1%) were normal
      at 1 month and at 2 years of age. CONCLUSIONS: Our data confirm those of previous
      reports as to the characteristics and outcome of MVM. In the setting of mild
      fetal ventriculomegaly with a normal karyotype and an absence of malformations,
      the outcome appears to be favorable.

PMID- 15980642
TI  - Management of delayed-interval delivery in multiple gestations.
AB  - OBJECTIVE: Proving that delayed delivery is possible, debating its modality,
      suggesting a guideline for its managing. METHOD: Six cases of delayed delivery
      were treated at the Maternity Hospital of Nancy, between 1979 and 2001, and the
      results were compared to a literature review of 148 found thanks to Medline
      database. RESULTS: Delayed delivery reduces the risk of neonatal mortality and
      morbidity. The delivery interval is 2-93 (median 7) days in our experience and 2
      153 (median 31) days in the literature. After the first expulsion, cerclage was
      used in 60% of the cases, prophylactic tocolysis and antibiotics in 79% and 71%,
      respectively. CONCLUSION: There is no consensus for its management but it must be
      performed with precise conditions to restrict both maternal and fetal risks. Our
      study is supporting an interventionist attitude with cerclage, prophylactic
      tocolysis and antibiotics.

PMID- 15980643
TI  - Congenital cervical rhabdomyosarcoma arising in one fetus of a twin pregnancy.
AB  - OBJECTIVE: To describe a huge congenital cervical rhabdomyosarcoma. METHODS: We
      were recently confronted with a case of fetal solid neck mass arising in one
      fetus of a twin pregnancy. Prenatally, the cervical tumor was consistent with
      teratoma, but it was diagnosed histologically as a rhabdomyosarcoma. Genetic
      amniocentesis showed a mosaic pattern consisting of
      46,XY/46,XY,t(2;8)(q35;q21.2). RESULTS: EXIT procedure was proposed to the
      parents but declined. The twin with huge cervical tumor died in utero at 35
      weeks' gestation due to hydrops fetalis. CONCLUSION: Fetal cervical
      rhabdomyosarcoma is an extremely rare condition that has not been previously
      reported, but should be considered in the presentation of fetal solid neck mass.

PMID- 15980644
TI  - Prenatal diagnosis of cloverleaf skull: watch the hands!
AB  - Pfeiffer syndrome is an extremely rare autosomal-dominant condition whose
      prenatal diagnosis has only been reported 6 times, mainly on the basis of a fetal
      cloverleaf skull deformity. Three types have been described, each with a
      different prognosis. This case report stresses the need to thoroughly analyze the
      fetus and particularly the fetal hands in case of prenatal observation of a
      cloverleaf skull. The discovery of characteristic hand abnormalities allowed the
      early prenatal detection of type 2 Pfeiffer syndrome in our patient.

PMID- 15980645
TI  - Maxillo-nasal dysplasia (binder syndrome): antenatal discovery and implications.
AB  - Binder syndrome (BS) or maxillo-nasal dysplasia is an uncommon developmental
      anomaly affecting primarily the anterior part of the maxilla and nasal complex.
      The characteristic findings are a failure of development in the premaxillary area
      with associated deformities of the nasal skeleton and the overlying soft tissues.
      Affected individuals typically have an unusually flat, underdeveloped midface
      (midfacial hypoplasia), with an abnormally short nose and flat nasal bridge,
      underdeveloped upper jaw, relatively protruding lower jaw and/or a 'reverse
      overbite' (or class III malocclusion). A case of BS was diagnosed at 24 weeks of
      gestation using two- and three-dimensional ultrasound. The first sign was an
      isolated flattened fetal nose in the mid-sagittal plane. Further ultrasound
      imaging showed the absence of the naso-frontal angle, giving impression of flat
      forehead and small fetal nose. We discuss about this entity.

PMID- 15980646
TI  - Success rate for culture of fetal postmortem tissue is dependent on the method of
      pregnancy termination.
AB  - OBJECTIVE: To determine the effect of different methods of pregnancy termination
      on the culture success rate of postmortem fetal tissue. METHODS: In a randomized
      trial, umbilical cord specimens were collected in a standardized manner and
      culture success rates were compared according to the method of pregnancy
      termination. RESULTS: There was a significantly higher culture success rate in
      the vaginal (90.0%) and oral misoprostol (83.0%) groups compared to the intra
      amniotic injection of prostaglandin group (52.8%). CONCLUSION: The results of our
      study and the very high success rate reported by others from specimens following
      dilatation and evacuation lead us to suggest that exposure to drugs used to
      induce abortion may be a more important factor in culture failure than either
      tissue type or time in transit.

PMID- 15980647
TI  - Antenatal treatment of chylothorax and cystic hygroma with OK-432 in nonimmune
      hydrops fetalis.
AB  - OBJECTIVES: To present our experience of using OK-432 in treating fetal cystic
      hygroma and chylothorax complicated with nonimmune hydrops fetalis. METHODS: OK
      432 (Picibanil) was injected into the fetal pleural cavity or fetal cystic
      hygroma. RESULTS: Patient 1: A 23-year-old, gravida 2, para 1, was found to have
      a recurrent fetal chylothorax at GA 29 weeks. Serial amnioreduction and
      thoracocentesis was performed at GA 31, 32, 33, and 34 weeks. Intrapleural OK-432
      injection was performed twice at GA 33 and 34 weeks. Cyanosis and respiratory
      distress were noted immediately after birth (GA 34 weeks). The baby expired
      despite of aggressive neonatal resuscitation. Patient 2: A 26-year-old, gravida
      2, para 1, was found to have a cystic hygroma of her fetus at GA 17 weeks.
      Karyotype of the cystic fluid and the amniocytes were 46, XY. Fetal ascites
      developed at GA 22 weeks. OK-432 injection into the tumour was performed at GA 23
      weeks. Stabilization of the cystic hygroma was noted throughout the pregnancy
      (about 3.5 cm in diameter). Serial fetal paracentesis and/or amnioreduction were
      performed. Karyotype of the ascites was again 46, XY. Maternal dietary
      modification with medium chain triglyceride was also prescribed. Chylothorax
      developed and the baby was born by cesareans at GA 32 weeks. Resolution of
      pleural effusion, ascites, and regression of cystic hygroma were noted since the
      2nd day after birth. The baby had survived beyond 4 months of age at submission.
      CONCLUSION: Combination of antenatal OK-432 injection, maternal dietary
      modification, serial thoracocentesis plus paracentesis, together with
      amnioreduction and tocolysis, appeared to contribute to the success of antenatal
      treatment. Fetal pulmonary expansion may determine the immediate neonatal
      survival.

PMID- 15980648
TI  - Impact of continuous intraoperative monitoring on outcomes in open fetal surgery.
AB  - OBJECTIVES: There are shifts in fetal hemodynamics during open fetal surgery that
      were not appreciated until the use of intraoperative fetal echocardiography. We
      have developed an intraoperative monitoring strategy to continuously assess fetal
      hemodynamics. We hypothesized that this approach would enhance intraoperative
      management and survival. METHODS: Medical records of open fetal surgery patients
      were reviewed since the implementation of this approach. Intraoperative fetal
      monitoring was accomplished by continuous echocardiography, pulse oximetry,
      establishment of intravenous access, and arterial blood gas and hemoglobin
      measurement. Overall survival was compared to fetal surgeries performed prior
      implementation of this monitoring strategy. RESULTS: Resections of a congenital
      cystic adenomatoid malformation or a sacrococcygeal teratoma in nine hydropic
      fetuses were performed while using this monitoring strategy. Intraoperative
      echocardiography resulted in a change of management in 7 of 9 fetuses. The main
      observations on fetal echocardiography resulting in intraoperative intervention
      were decreased ventricular filling, bradycardia, and decreased ventricular
      contractility. Therapy included administration of volume expanders and/or
      inotropic agents. Overall fetal survival was 78% compared to a survival of 42%
      prior to the implementation of this approach. CONCLUSION: Continuous
      intraoperative fetal monitoring provides real time assessment of fetal
      hemodynamics which results in changes in intraoperative management. The overall
      outcomes in these critically ill fetuses have been improved.

PMID- 15980649
TI  - Age influences the expression of GAP-43 in the rat hippocampus following seizure.
AB  - BACKGROUND: Normal aging is associated with impairments in learning and memory
      and motor function. One viable hypothesis is that these changes reflect an age
      related decrease in brain plasticity. OBJECTIVE: The aim of the present study was
      to identify age-related changes in the time course of expression of the axonal
      growth associated protein 43 (GAP-43) in a rat model of brain plasticity.
      METHODS: We examined by Northern blotting, in situ hybridization, and
      immunohistochemistry the effects of age on the time course of the expression GAP
      43 following pentylenetetrazole-induced seizure in the hippocampus of 3-, 18-,
      and 28-month-old rats. RESULTS: In this model of brain plasticity, young rats
      displayed a decrease in GAP-43 mRNA levels in CA1, CA3, and polymorphic regions,
      lasting from 10 h to 3 days after seizure. This was followed by recovery, with
      peak expression between days 10 and 20. The baseline levels of GAP-43 mRNA
      decreased with age, especially in the CA3 region. Despite lower baseline levels,
      middle-aged rats showed the same pattern of upregulation of GAP-43 mRNA
      expression as the young animals. Old rats showed only minimal upregulation,
      however, and this occurred only in the polymorphic layer. The level GAP-43
      protein itself was higher in old control rats than in the other two control
      groups, a condition that was transiently reversed by seizure activity.
      CONCLUSIONS: Middle-aged rats are still capable of a sustained, though
      diminished, response to seizure activity, while old rats lose this ability.
      Disruption of the temporal and anatomical coordination of expression of GAP-43
      may contribute to the general decline in brain plasticity with age.

PMID- 15980650
TI  - On how insulin may influence ageing and become atherogenic throughout the insulin
      like growth factor-1 receptor pathway: in vitro studies with human vascular
      smooth muscle cells.
AB  - BACKGROUND: It is known that growth factors play a role in ageing and
      atherogenesis, and insulin develops mitogenic activity in vitro. OBJECTIVES: This
      study focuses on the pathway by which insulin induces proliferation and mobility
      in vascular smooth muscle cells (SMCs) compared with that of insulin-like growth
      factor-1 (IGF-1), because they are two basic phenomena for atherogenesis that
      could also help to understand the role of insulin in the ageing process. METHODS:
      Bromodeoxyuridine DNA incorporation, chemotaxis and the appearance of membrane
      ruffles were measured in cultured SMCs after incubation with insulin or IGF-1 in
      the presence of insulin or IGF-1 receptor-blocking antibodies. RESULTS: Insulin
      induced SMC proliferation through the IGF-1 receptors; indeed, the blockade of
      insulin receptors does not inhibit the mitogenic influence of insulin. On the
      contrary, insulin-induced cell migration was inhibited by blocking the insulin
      receptor but not the IGF-1 receptor. Nevertheless, in less differentiated SMCs
      from non-confluent cultures, the migratory response was significantly higher and
      insulin lost its receptor specificity. It was stimulated through receptors both
      for insulin and IGF-1. In these cases the IGF-1 action was similar. Insulin
      induced F-actin rearrangements took place through both types of receptors, but
      IGF-1 was a little more specific through its own receptors. CONCLUSION: The
      pathway activated by insulin to induce SMC proliferation is not different from
      that of IGF-1, whereas the unspecific mechanism inducing mobility in growing
      cells seems to be related to a higher sensitivity response. Cells with the
      highest mitotic activity have the highest mobility in which stimulation of
      receptor specificity is lost for either insulin or IGF-1. Extrapolating these
      results to in vivo, insulin could become relevant for inducing stabilization and
      also side effects in ageing.

PMID- 15980651
TI  - Age-dependent change of uric acid level in the dermis using cutaneous
      microdialysis.
AB  - BACKGROUND: We had proposed the usefulness of cutaneous microdialysis for the
      study of antioxidants in the skin. OBJECTIVE: We designed a study analyzing the
      level of uric acid in the skin, one of the major antioxidants, for an age
      dependent change. METHODS: 16 healthy male volunteers were divided into two
      groups according to age. Eleven subjects were in their 3rd decade, under 30 years
      of age (young group) and the others were their 8th decade (old group), over 70
      years of age. Dialysate samples were analyzed using high-performance liquid
      chromatography analysis. RESULTS: In the young group the mean level of uric acid
      was 31.9+/-16.1 microg/ml, while in old group it was 13.4+/-5.2 microg/ml.
      CONCLUSION: This result demonstrated an in vivo state of antioxidant level in the
      human skin and the age-dependent difference was concordant with other in vitro or
      ex vivo studies; therefore, cutaneous microdialysis could be used in analysis and
      monitoring studies including human antioxidants and anti-aging.

PMID- 15980652
TI  - Clinical features of elderly patients submitted to coronary artery bypass graft.
AB  - OBJECTIVE: To describe the clinical features as well as morbidity and mortality
      of elderly patients submitted to coronary artery bypass graft (CABG). DESIGN:
      Randomized, single-center, observational study. METHODS: A prospective study was
      carried out in a tertiary referral teaching hospital (Heart Institute-Brazil). A
      total of 220 inpatients submitted to elective CABG were evaluated and data
      collected from the pre-, intra- and postoperative periods. INSTRUMENTS: The
      patients were assessed according to the Geriatric Depression Scale. A diagnosis
      of delirium was determined according to DSM-IV criteria. RESULTS: Of these 220
      patients 64.5% were males and 35.5% females. The mean age was 71 years. The most
      important preoperative findings were a higher incidence of comorbidities such as
      hypertension (73%), diabetes mellitus (35%), dyslipidemia (27%), and previous
      myocardial infarction (41%). The majority of patients were found to have three or
      more vessels obstructed at angiography (74%). The major intraoperative findings
      were that a high number of the patients received more than 3 grafts (74%). A
      large proportion (72%) of patients needed a blood transfusion and the overall
      incidence of clinical complications was 33%. The overall postoperative mortality
      rate for this observational study was 5%. A large number of patients presented
      complications (56%) such as hypotension (22%), atrial fibrillation (22%), and
      delirium (34%). CONCLUSIONS: Although elderly patients have a somewhat increased,
      however acceptable, operative mortality rate, we believe that this patient group
      can benefit from CABG.

PMID- 15980653
TI  - Clinical outcome of salmon calcitonin nasal spray treatment in postmenopausal
      women after total hip arthroplasty.
AB  - OBJECTIVE: The increasing rate of hip fractures is giving rise to a number of
      socio-economic problems for the aging community. In addition to being unable to
      resume their previous living habits, many patients fail to achieve full
      functional recovery after the fractures. Total hip arthroplasty (THA) is a
      successful operation for the majority of patients with all forms of hip
      fractures, being performed increasingly often throughout the world. Revision
      rates for THA range up to 20% per year. Aseptic loosening is the reason for 75%
      of the revisions. An additional problem post-THA is the rate of heterotopic soft
      tissue calcification after THA, resulting in severely impaired function, pain,
      and a reduced range of hip movement. SUBJECTS: In an open study, 37 women who had
      undergone cementless THA after accidental hip fractures were treated twice daily
      with 200 IU of salmon calcitonin nasal spray for 12 months. Simultaneously the
      patients received one bag of 1,000 mg calcium plus 880 IU vitamin D daily
      throughout the treatment period of 1 year. A parallel group of 38 women with a
      similar clinical status in terms of hip fractures and cementless THA were treated
      with only one bag of 1,000 mg calcium plus 880 IU vitamin D daily through the
      treatment period. RESULTS: The results of this 12-month clinical trial show that
      200 IU of salmon calcitonin nasal spray per day significantly improves the
      clinical outcome of postmenopausal elderly women following THA. Treatment with a
      salmon calcitonin nasal spray significantly reduces bone turnover, loss of bone
      density, and pain. The functional status of the patients was improved and the
      risk of falling reduced by rehabilitation during the observation period of 12
      months. Additionally, calcitonin promoted the repair of hip fractures and was
      associated with a significantly lesser rate of refractures as well as
      periprosthetic ossifications. CONCLUSION: The increasing revision rate for THA
      during the first year and the patient's problem of resuming their previous living
      habits are the main foci of our study. Calcitonin nasal spray seems to cause few
      side effects. The additive treatment appears to improve the clinical outcome of
      THA in elderly postmenopausal women.

PMID- 15980654
TI  - Biochemical changes in response to intensive resistance exercise training in the
      elderly.
AB  - BACKGROUND: It is assumed that low-grade inflammation, characterized by increased
      circulating IL-6 and TNF-alpha, is related to the development of sarcopenia.
      Physical exercise, especially high intensity resistance training, has been shown
      to be effective in restoring the strength deficit in the elderly. Intensive
      exercise is accompanied by significant release of IL-6 and TNF-alpha into the
      blood circulation, but does not result in muscle wasting. Exercise-induced
      changes in heat-shock protein (Hsp), responsible for cellular protection during
      stressful situations, might interfere with the acute phase reaction and muscle
      adaptation. OBJECTIVE: To investigate if intensive strength training in elderly
      persons induces changes in Hsp70 expression, and if these changes are related to
      changes in the acute phase reaction or muscle adaptation. METHODS: 31 elderly
      persons (aged 68.4+/-5.4 years) performed 6 weeks' intensive strength training.
      At baseline and after 6 weeks, muscle strength, functional performance (physical
      activity profile, 6-min walk, 30- second chair stand, grip strength, chair sit &
      reach and back scratch), linear isokinetic leg extension, circulating IL-6, TNF
      alpha, IL-10 and TGF-beta, and Hsp70 in monocytes (M) and lymphocytes (L)
      immediately after sampling (IAS), after incubation at 37 and 42 degrees C were
      determined. In 12 participants, cytokines were determined in untrained and
      trained conditions before and after a single training session. RESULTS: After 6
      weeks' training, muscle strength and functional performance improved
      significantly, together with decreased Hsp70 IAS and Hsp70 37 degrees C and
      increased Hsp70 42 degrees C (all p<0.05). Strength gains correlated positively
      with baseline Hsp70 37 degrees C and training-induced changes of Hsp70 42 degrees
      C in M and L. In an untrained condition, training induced an increase of IL-6
      (p<0.05) and a tendency of IL-10 to decrease (p=0.06). In a trained condition the
      decrease of IL-10 disappeared. Baseline physical activity and 6-min walk distance
      correlated negatively with circulating IL-6 (p<0.05); except for a negative
      correlation between TGF-beta and Hsp70 37 degrees C L (p<0.05), no significant
      relationships were found between cytokines and Hsp70. After the training program,
      Hsp70 37 degrees C was negatively related to circulating TNF-alpha, IL-10 and TGF
      beta. CONCLUSION: Strength training in the elderly induces changes in Hsp70
      expression, associated to strength gains and circulating cytokines.

PMID- 15980655
TI  - Effects of aging on visual attentional focusing.
AB  - BACKGROUND: Visual attentional performance is affected by aging, but there are
      methodological barriers to the understanding of this phenomenon that are due,
      above all, to the concomitant deterioration of sensory or central factors such as
      visual acuity and information processing speed. OBJECTIVE: The aim of the present
      study was to verify the effects of aging on visual attentional focusing by
      analyzing the space- and object-based components as well as the exogenous and
      endogenous dimensions of the attentional allocation. METHODS: Focusing of visual
      attention was investigated in 14 youngsters, 14 younger adults and 14 older
      adults (age ranges 12-15, 24-38 and 60-75 years, respectively). In two
      discrimination reaction time (RT) experiments, attention was cued by means of
      spatial cues of different size followed by compound stimuli at a shorter (150 ms)
      and a longer (500 ms) stimulus-onset asynchrony (SOA). The compound stimuli
      contained a predefined target letter at a local or global level. RESULTS: Older
      adults showed generally slower RTs and higher rates of delayed responses than
      younger individuals and reduced discrimination speed of local objects at 150-ms
      SOA, particularly when attention was invalidly cued to focus at a larger spatial
      scale. CONCLUSIONS: This pattern of results suggests that aging causes a
      dysfunction of the space-based and the object-based components of the attentional
      'zooming in'. Such information may be of practical relevance for developing
      attentional training programs for older adults.

PMID- 15980656
TI  - Forgetting numbers in old age: strategy and learning speed matter.
AB  - BACKGROUND: Memory intervention research with older adults has primarily focused
      on immediate effects of training. Little is known about whether memory training
      can prevent forgetting of a learned material over time. OBJECTIVE: The main
      purpose of this study was to investigate the effects of memory training on
      forgetting of numerical information in old age. In addition, the effect of speed
      of learning on forgetting rate was examined. METHODS: Two training programs were
      employed contrasting a number-consonant mnemonic strategy with a self-generated
      strategy. A non-practice control group was also included. There were 20
      participants in each group (age range=60-83 years). Following completion of
      training, participants memorized six 4-digit numbers to perfection. Retention was
      tested after 30 min, 24 h, 7 weeks, and 8 months. RESULTS: The three groups
      showed equal rates of forgetting across the first two follow-up assessments. A
      different picture emerged for the last two occasions, with the self-generated
      strategy group remembering more items relative to the two other groups. Moreover,
      participants reaching the criterion in few trials exhibited less forgetting than
      slow learners. CONCLUSIONS: These data indicate that self-generated strategy
      training may have advantages over learning a classical mnemonic for preventing
      long-term forgetting of numeric materials in old age.

PMID- 15980657
TI  - Response to Article by Netz and Coworkers, vol 50, pp 121-126.

PMID- 15980658
TI  - Impact of menopause on the augmentation of arterial stiffness with aging.
AB  - BACKGROUND/AIMS: Aortic stiffness, determined by pulse wave velocity (PWV), is an
      independent marker of cardiovascular risk. PWV is mainly influenced by age
      associated alterations in arterial wall structure and blood pressure. The present
      study was conducted to assess the impact of menopause on the brachial-ankle PWV
      (baPWV) in healthy women. METHODS: Fifty premenopausal women aged 22-54 years and
      40 postmenopausal women aged 40-73 years were recruited for this study. Subjects
      with hypertension, diabetes, and hyperlipidemia were strictly excluded. The
      results of baPWV were analyzed chronologically by 10- or 5-year age intervals.
      RESULTS: There was no significant difference in baPWV between premenopausal and
      postmenopausal women in their 40s and 50s. The baPWV of postmenopausal women aged
      over 60 years was significantly higher than that of postmenopausal women in their
      50s. To clarify the age-dependent elevation in baPWV in detail, women their 50s
      and 60s were divided into subgroups by 5-year age intervals. There was no
      significant difference in baPWV among the 50-54-, 55-59- and 60-64-year
      subgroups. baPWV significantly increased in the 65-69- year subgroup (p< 0.05).
      There was a significant relationship between baPWV and age in premenopausal (r =
      0.452, p = 0.001) and postmenopausal (r = 0.581, p < 0.0001) women. The slope of
      the regression line for baPWV plotted against age was steeper in postmenopausal
      than in premenopausal women. CONCLUSIONS: This study produces suggestive evidence
      that menopause amplifies the age-dependent increase in arterial stiffness.

PMID- 15980659
TI  - Mutations of the SPINK1 gene and their relation to chronic pancreatitis.

PMID- 15980660
TI  - 'Do experiments that will help solve clinical problems'. An interview with
      Professor Seiki Matsuno by Martin E. Fernandez-Zapico.
AB  - In the current interview, Professor Seiki Matsuno shares his experience and
      provides career advice to young investigators initiating in pancreatic research.
      Professor Matsuno is internationally recognized for his contributions to
      different areas of pancreatology, including the clinical characterization and
      treatment of pancreatic diseases.

PMID- 15980662
TI  - Current status of laparoscopic biliary bypass in the management of non-resectable
      peri-ampullary cancer.
AB  - BACKGROUND: In patients with non-resectable peri-ampullary cancer, optimization
      of quality of life is an important goal. Although endoscopic palliation is widely
      used, the proponents of laparoscopic biliary bypass claim that this procedure
      alters management towards surgery. However, the evidence base for selection of
      laparoscopic bypass is limited and the aim of this report is to scrutinize the
      available evidence in order to assess the current role of this procedure.
      METHODS: A computerised literature search was made of the Medline database for
      the period from January 1966 to December 2004. Searches identified 12 reports of
      laparoscopic palliation for peri-ampullary cancer. These reports were retrieved
      and data analysed in the following categories: type of bypass; combination with
      other procedures; complication and outcome. RESULTS: Laparoscopic
      cholecystoenterostomy is the commonest form of laparoscopic biliary bypass
      practiced. Of the 52 reported cases undergoing laparoscopic biliary bypass, 40
      underwent laparoscopic cholecystojejunostomy, 6 laparoscopic
      choledochoduodenostomy and 6 underwent laparoscopic hepaticoje- junostomy.
      CONCLUSION: Current evidence does not justify the incorporation of laparoscopic
      biliary bypass techniques into contemporary evidence-based management algorithms
      for patients with non-resectable periampullary cancer.

PMID- 15980663
TI  - Pathologic alterations detected in acute pancreatitis induced by sodium
      taurocholate in rats and therapeutic effects of curcumin, ciprofloxacin and
      metronidazole combination.
AB  - BACKGROUND AND AIMS: Secondary bacterial infections and free radical injury have
      been known to play an important role in the pathogenesis and clinical outcome of
      acute pancreatitis. Despite the therapy models developed in recent years, the
      mortality rate is still reported to be higher than expected. The objective of
      this study therefore was to investigate the effectiveness of ciprofloxacin and
      metronidazole combination and curcumin together in the treatment of acute
      pancreatitis. METHODS: Acute pancreatitis was induced in rats by sodium
      taurocholate (n = 60). Starting 6 h after the induction of acute pancreatitis,
      groups I and II were injected 200 mg/kg ciprofloxacin and 500 mg/kg metronidazole
      intraperitoneally every 12 h for 6 days. Groups II and III received 100 mg/kg
      curcumin since day 20 prior to the initiation of acute pancreatitis. On day 6,
      animals of all groups were killed. Blood and tissue samples were taken for
      biochemical, pathologic and bacteriologic examination. RESULTS: No statistical
      difference in the treatment groups versus the non-treatment group has been
      detected in the pancreatic tissue on the basis of histopathological scoring
      results. Prevalences of bacterial translocation were significantly lower in the
      treatment groups (groups I-III) than in the non-treatment group (group IV) (p <
      0.001, p < 0.001, p < 0.05, respectively). Serum amylase, lipase, malon
      dialdehyde and nitric oxide (except for nitric oxide level in group I), levels of
      groups I, II and III were significantly lower than those of group IV (p < 0.05).
      CONCLUSIONS: The administration of ciprofloxacin and metronidazole in combination
      and curcumin in acute pancreatitis failed to provide a preventive effect on the
      occurrence of tissue injury, whereas free radical injury and prevalence of
      bacterial translocation were reduced significantly.

PMID- 15980664
TI  - Mutations in the serine protease inhibitor Kazal Type 1 (SPINK1) gene in Japanese
      patients with pancreatitis.
AB  - BACKGROUND/AIMS: Recent studies have shown an association between the N34S
      mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene and chronic
      pancreatitis (CP). We here examined the prevalence of SPINK1 mutations in
      Japanese patients with pancreatitis. METHODS: Genomic DNA was prepared from 80
      Japanese patients with CP, 36 patients with acute pancreatitis (AP), and 165
      healthy controls. All exons and the promotor region of the SPINK1 gene were
      amplified by the polymerase chain reaction, and directly sequenced. RESULTS: We
      found four types of mutation (N34S, IVS1-37T>C, -215G>A, and IVS3 + 2T>C) and two
      types of polymorphism (-253T>C and 272C>T). The N34S mutation cosegregated with
      IVS1-37T>C, and was present in 8 CP and 1 AP patients. The -215G>A mutation was
      in a complete linkage with IVS3 + 2T>C, and was present in 8 CP and 1 AP
      patients. The prevalences of [N34S; IVS1-37T>C] and [-215G>A; IVS3 + 2T>C] were
      significantly higher in patients with familial pancreatitis (38 and 13%,
      respectively) and with idiopathic CP (13 and 16%) than normal subjects (0.6 and
      0%). In addition, the frequency of [N34S; IVS1-37T>C] mutation was higher in
      patients with autoimmune CP (33%). CONCLUSION: The SPINK1 gene mutations were
      associated with pancreatitis also in Japan.

PMID- 15980665
TI  - Cyclooxygenase-2 expression associated with severity of PanIN lesions: a possible
      link between chronic pancreatitis and pancreatic cancer.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is a key modulatory molecule in inflammation
      and neoplasia. Increasing evidence suggests a role for COX-2 in pancreatic cancer
      (PAC). However, expression of COX-2 in pancreatic intraepithelial neoplasia
      (PanIN), the precursor lesion of PAC which is often present in chronic
      pancreatitis (CP), has received little attention. METHOD: COX-2 immunostaining
      was performed on sections of PAC (n = 26), CP (n = 34), PanIN (n = 68) and normal
      pancreas (n = 11). Sections were also stained for macrophages (CD68), activated
      pancreatic stellate cells (alphaSMA), and collagen (Sirius Red) as markers of
      fibrosis. Semiquantitative scoring was based on the extent and intensity of
      immunostaining. RESULTS: COX-2 expression was increased in PAC compared to normal
      (p = 0.02) with 89% of cases exceeding COX-2 immunostaining in normal ducts. In
      PanIN lesions, COX-2 expression increased with escalating severity of the PanIN
      change (p < or = 0.01). COX-2 expression was increased in PanIN-2/3 compared to
      normal pancreas and CP (p < or = 0.001). In ducts of CP, COX-2 expression did not
      differ from that in normal tissue. There was no association between COX-2
      expression and clinicopathological variables. CONCLUSION: The high level of COX-2
      expression in PanIN lesions suggests that this enzyme could be a therapeutic
      target at a non-invasive stage of pancreatic carcinogenesis and feasible for
      chemoprevention in CP.

PMID- 15980666
TI  - Intravenous antioxidant modulation of end-organ damage in L-arginine-induced
      experimental acute pancreatitis.
AB  - BACKGROUND: Oxidative stress mediates acinar injury in experimental acute
      pancreatitis (AP) and antioxidants are depleted in human AP. This study tests the
      hypothesis that exogenous antioxidant supplementation ameliorates experimental
      AP. METHODS: Male Sprague-Dawley rats were randomly allocated to 1 of 4 groups (n
      = 5/group) and sacrificed at 72 h. AP was induced by 250 mg per 100 g body weight
      of 20% L-arginine hydrochloride in 0.15 mol/l sodium chloride. Group allocations
      were: group 1 (control) no intervention; group 2 AP; group 3 early multiple
      antioxidant (MAOX) intervention comprising 15 microg/kg selenium, 30 microg/kg
      ascorbate and 300 mg/kg N-acetylcysteine given at 6 and 30 h and group 4 the MAOX
      combination above given at 24 and 48 h. Endpoints were: serum amylase,
      antioxidant levels, bronchoalveolar lavage (BAL) protein and lung myeloperoxidase
      (MPO) activity and histological assessment of pancreatic injury. RESULTS: L
      arginine induced AP characterised by oedema, neutrophil infiltration, acinar cell
      degranulation and elevated serum amylase. Early MAOX reduced pulmonary MPO and
      BAL protein and reduced acinar swelling, degranulation and pancreatic parenchymal
      infiltration by inflammatory cells. These features were absent when intervention
      was delayed. CONCLUSION: In this model, early but not late antioxidant
      intervention ameliorates pancreatic and pulmonary injury.

PMID- 15980667
TI  - Different capabilities of morphological pattern formation and its association
      with the expression of differentiation markers in a xenograft model of human
      pancreatic cancer cell lines.
AB  - AIMS: New concepts of tumorigenesis favor an unregulated process recapitulating
      different stages of embryogenic development with dysregulation of transition
      states. The aim of our study was to investigate the possibility of
      differentiation pathways of human pancreatic cancer cell lines in vivo. MATERIAL
      AND METHODS: Different human pancreatic cancer cell lines (YAPC, DAN-G, CAPAN-1,
      PANC-1 and MIA PaCa-2) were implanted subcutaneously (3 x 10(6) cells) for 28
      days in nude mice. Xenotransplants were characterized with histochemistry (HE,
      PAS), immunohistochemistry (cytokeratin (CK)7, CK8, CK18, CK19, CK20, vimentin,
      chromogranin A (Chr-A), alpha1-antichymotrypsin (alpha1-chym), beta-catenin,
      laminin-5, pancreatic and duodenal homeobox gene 1 (pdx-1), sonic hedgehog
      protein (shh), Patched (ptc)), Western blotting and real-time PCR (CK7, CK8,
      CK20, Chr-A, pdx-1, shh, ptc). RESULTS: Depending on three major morphologic
      phenotypes of tumor cell xenotransplants (ductal (YAPC), ductal/solid (DAN-G,
      CAPAN-1), solid (PANC-1, MIA PaCa-2)), a decrease of CK7/CK19 was found,
      accompanied by an increase of CK8/18 and vimentin. Predominantly the CK7-positive
      ductal phenotype (YAPC and DAN-G) was associated with pdx-1 expression, whereas
      the CK8-positive solid phenotype was associated with shh/ptc expression on
      protein and mRNA level. Additionally, CK-20 expression was mainly linked to the
      ductal phenotype, co-localized with nuclear beta-catenin. The endocrine-exocrine
      transdifferentiation, as assessed by Chr-A and alpha1-chym, was on a constant low
      to moderate level in all xenotransplants. Finally, an intensive epithelial
      mesenchymal interaction was observed by overexpression of laminin-5 at the
      invasion front. CONCLUSION: The observed patterns of morphology and molecular
      differentiation in human pancreatic cancer xenografts indicate that these cancer
      cell lines have different capabilities of pattern formation in vivo associated
      with molecular differentiation markers, especially of embryonic pancreatic
      development.

PMID- 15980668
TI  - [Nutritional assessment and management in liver cirrhosis].

PMID- 15980669
TI  - [Problems and prospects of stem cells for clinical use in hepatology].

PMID- 15980670
TI  - [Association between CCR5 promoter polymorphisms and hepatitis B virus
      infection].
AB  - BACKGROUND/AIMS: Immunogenetic factors may play a role in determining the
      susceptibility of an individual to viral infection. CCR5 promoter polymorphisms
      are known to be associated with HIV infection. However, there has been no report
      on the association between CCR5 promoter polymorphism and HBV infection.
      Therefore, we investigated the relationship between the CCR5 promoter
      polymorphism and HBV infection. METHODS: A total of 377 patients were classified
      into two groups according to their HBV infection status: (1) the spontaneous
      clearance group (SC); HBsAg (-), anti-HBc (+), anti-HBs (+) (2) the chronic HBsAg
      (+) carrier group (CC); HBsAg (+), anti-HBc (+), anti-HBs (-). CCR5 polymorphisms
      were detected by employing matrix-assisted laser desorption/ionization time of
      flight mass spectrometry (MALDI-TOF MS)- based SNP scoring assay, termed
      Restriction Fragment Mass Polymorphism (RFMP), which exploits the differences in
      molecular masses between the common allele and rare allele bases of interest.
      RESULTS: We found that the genotype frequencies of CCR5 A59029G significantly
      differed between the SC group (n=138) and CC group (n=239) (P<0.05). The CCR5
      59029A allelic genotype was associated with an increased risks of chronic
      infection rather than spontaneous clearance (P=0.002), and the presence of the
      CCR5 59029G allele was significantly associated with the spontaneous clearance of
      HBV (P=0.001). Strong linkage disequilibrium between the CCR5-59029 and the CCR5
      59353 polymorphic variants was identified. None of the 377 subjects had the CCR5
      32 bp deletion mutation. CONCLUSIONS: The CCR5 promoter polymorphisms at position
      59029 might play a role in the clearance of HBV infection. This primary
      experimental evidence needs further studies to clarify the clinical usefulness of
      CCR5 promoter polymorphisms as a target for the screening or treatment of HBV
      infection.

PMID- 15980671
TI  - [Efficacy and safety of adefovir dipivoxil in patients with decompensated liver
      cirrhosis with Lamivudine resistance compared to patients with compensated liver
      disease].
AB  - BACKGROUND/AIMS: Adefovir dipivoxil is effective in patients with lamivudine
      resistant hepatitis B virus (HBV). However, little is known about its role in
      Korean patients with decompensated liver cirrhosis. We retrospectively evaluated
      the efficacy and safety of adefovir dipivoxil in patients with decompensated
      liver cirrhosis with lamivudine resistance, and we compared this to the patients
      having compensated liver disease. METHODS: The patients with lamivudine-resistant
      chronic liver disease were enrolled and they received adefovir dipivoxil 10 mg
      daily. The clinical course and the biochemical and virological response of the
      decompensated cirrhosis group were compared with those of the patients with
      compensated liver disease group. RESULTS: One-hundred and one patients (the
      decompensated cirrhosis group, n=53; the compensated liver disease group, n=48)
      were evaluated. During the following up, 13 patients in the decompensated group
      and 4 patients in the compensated group dropped out of the treatment (P=0.011).
      After adefovir treatment, the proportion of patients with serum HBV DNA below 0.5
      pg/mL in the decompensated group was less than that in the compensated group
      (50.9% vs. 83.3%, P=0.001), but the rates of normalized ALT, HBeAg loss and HBeAg
      seroconversion did not differ. The change of the Child-Pugh score in the
      decompensated group was 9.1 +/- 1.8 to 6.9 +/- 1.6 (P<0.001). The biochemical
      response in decompensated group was slower than that in the compensated group.
      Renal toxicity was not observed in either group. CONCLUSIONS: These results
      suggest that adefovir dipivoxil would be an effective and safe treatment for
      patients with decompensated liver cirrhosis with lamivudine resistance, but its
      effect might be limited and slower for decompensated cirrhosis.

PMID- 15980672
TI  - [Antioxidant status in nonalcoholic steatohepatitis].
AB  - BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is chronic liver disease
      that can potentially progress to end stage liver disease. Oxidative stress to the
      vulnerable fatty liver has been reported as a key mechanism in development of
      NASH. Several antioxidant pathways have been identified, but reports that
      involved quantitative analysis of each antioxidant systems are rare, and these
      reports have shown various results. So, we investigated antioxidant status and
      the degree of oxidative stress by measuring several antioxidant enzymes, the
      total antioxidant status (TAS), and the metabolites of superoxide in NASH
      patients. METHODS: Nineteen NASH patients who were confirmed by liver biopsy and
      fifteen controls were involved in this study. The levels of body mass index
      (BMI), AST, ALT, superoxide dismutase (SOD), glutathione peroxidase (GPx),
      catalase, TAS, hydrogen peroxide (H2O2), and malondialdehyde (MDA) were compared
      between both groups. The relationship between the histologic severity and the
      levels of each antioxidants were analyzed in the NASH group. RESULTS: The
      activities of SOD and catalase were lower in the NASH group. The concentrations
      of TAS and H2O2 were higher in NASH group. The level of GPx and MDA showed no
      significant differences between both groups. There were no significant
      relationships between the above variables and the pathological severity.
      CONCLUSIONS: The disturbed metabolism of superoxide due to the decreased
      activities of SOD and catalase seem to be important in the pathogenesis of NASH.
      Further investigations about the nonenzymatic secondary antioxidant mechanism are
      necessary because the TAS was higher for the NASH group. The lack of difference
      between both groups for the concentration of MDA indicates that mechanisms other
      than lipid peroxidation also may be important in the pathogenesis of NASH.

PMID- 15980673
TI  - [Clinical characteristics of factory workers with asymptomatic liver function
      test abnormalities found on serial health examination].
AB  - BACKGROUND/AIMS: The liver function tests (LFTs), such as aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and gamma
      glutamyltranspeptidase (gamma-GT), have been widely used as screening tests but
      their low positive predictive value can cause many false positive results. To
      evaluate the clinical usefulness of these tests, we analyzed the serial LFT
      results for factory workers, and we compared the risk factors for the groups that
      were divided according to the serial LFT results. METHODS: From June 2001 to
      October 2001, 1223 consecutive healthy workers in a single factory were enrolled
      in our study; a questionnaire, LFT and liver ultrasonography were done for all
      the subjects. The previous LFT results were collected from the Annual health
      examination survey. According to the abnormalities on the serial LFT, the
      participants were classified into three groups (abnormal-in-both, alternating or,
      normal-in-both) and the risk factors were compared among these groups using
      multiple logistic regression analysis. RESULTS: The prevalence of LFT abnormality
      on a single test was 16.8%, but on the serial LFT, only 5% of the study
      participants showed consistent abnormality. The risk factors for the abnormal-in
      both group, compared with the alternating group, were liver ultrasonography
      abnormality such as a fatty liver (odds ratio, 2.2; P=0.026) and a heavy alcohol
      intake (more than 210 g/week) (odds ratio, 7.2; P=0.064). HBsAg was not a
      significant risk factor for any of the three groups. CONCLUSIONS: In factory
      workers having serial LFT abnormalities, alcoholic liver disease could be the
      principal cause of abnormal LFT. Even if the HBsAg were positive in patients with
      abnormal LFT, there is the possibility of another causes for LFT abnormalities
      such as alcoholic liver disease and non-alcoholic steatosis or steatohepatitis.

PMID- 15980674
TI  - [Effect of transjugular intrahepatic portosystemic shunt for variceal bleeding in
      hepatocellular carcinoma patients with portal vein thrombosis].
AB  - BACKGROUND/AIMS: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is commonly
      used in patients with variceal bleeding. However, this procedure is
      contraindicated in hepatocellular carcinoma patients with portal vein thrombosis.
      This study was done to evaluate the effect of TIPS in those patients with
      variceal bleeding. METHODS: Between 1997 and 2004, six hepatocellular carcinoma
      (HCC) patients with portal vein thrombosis were enrolled in this study due to
      their variceal bleeding. All the patients underwent TIPS placement to treat the
      variceal bleeding that had not responded to endoscopic treatment. Effective shunt
      creation was assessed by the decrease of the portal pressure gradient (less than
      12 mmHg) or if good patency and flow were seen on a doppler examination. RESULTS:
      Shunts were successfully created in all the patients and the bleeding was
      immediately controlled in the active bleeding cases. The bleeding was caused by
      esophageal varices in one patient and, by gastric varices in five patients. The
      HCC types were diffuse or massive in five patients, and a single nodule was
      present in one patient. All the patients had portal vein thrombosis. Rebleeding
      was noted in two patients at 10 days and 3 months, respectively, due to the shunt
      occlusion. Hepatic encephalopathy was noted in two patients. The causes of death
      were hepatorenal syndrome after 2 weeks in one patient, bleeding due to portal
      hypertensive gastropathy after 3 weeks in another, and cancer progression after 4
      months in third patient. CONCLUSIONS: For HCC patients with portal vein
      thrombosis, TIPS can be an effective treatment modality if uncontrolled variceal
      bleeding presents when using endoscopic hemostasis or pharmacologic therapy.
      However, further studies are needed.

PMID- 15980675
TI  - [Spontaneous resolution of vanishing bile duct syndrome in Hodgkin's lymphoma].
AB  - Cholestasis in a patient with Hodgkin's disease is uncommon, and the causes of
      cholestasis are mainly direct tumor involvement of the liver, hepatotoxic effects
      of drugs, viral hepatitis, sepsis and opportunistic infections. Vanishing bile
      duct syndrome (VBDS) represents a very rare cause for cholestasis in this
      disease. We report here on a case of a 45-year-old man who developed VBDS during
      the complete remission stage of Hodgkin's lymphoma. There was no history of
      hepatitis or intravenous drug abuse, and the patient had negative results for
      hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, and
      human immunodeficiency virus. The serological studies for antinuclear antibodies,
      anti-mitochondrial antibodies and anti-smooth muscle antibodies were also
      negative. Liver biopsy disclosed the absence of interlobular bile ducts in 9 of
      10 portal tracts without any active lymphocyte infiltration and there were no
      Reed-Sternberg cell in the liver. The patient's cholestasis was in remission and
      the serum bililrubin level was normalized after two months without treatment, but
      tumor recurrence was noted at multiple sites of the abdominal lymph nodes on
      follow-up abdomino-pelvic computed tomogram.

PMID- 15980676
TI  - [Four cases of hepatic fascioliasis mimicking cholangiocarcinoma].
AB  - Human fascioliasis is a zoonosis caused by Fasciola hepatica, and this is a
      trematode that infests cattle and sheep. Humans are accidental hosts in the life
      cycle of this parasite. People are infected by ingestion of the water or the raw
      aquatic vegetables that are contaminated with the metacercaria. This fluke's
      worldwide distribution occurs in areas where sheep, cattle and goats are raised,
      and there is a life-cycle niche for this fluke in lymnaeid snails. However, it is
      a rare disease in Korea. We experienced four human fascioliasis which were
      difficult to differentiate from hepatic malignancy in three patients, and this
      was misdiagnosed as common hepatic duct tumor in one patient. The patients
      manifested only vague abdominal symptoms. Intrahepatic fascioliasis showed
      multiple ill-defined hypoattenuating lesions and filling defects of the lesion
      lumens on radiologic study. A striking eosinophilia from the patients' blood was
      identified and a positive finding of a serum enzyme linked immunosorbent assay
      for the Fasciola hepatica was also noted in three of four patients. The
      therapeutic trial with triclabendazole and praziquantel was not successful.

PMID- 15980677
TI  - [Eosinophilic liver abscess].

PMID- 15980678
TI  - [Hepatocellular carcinoma with unusual metastasis to the gallbladder].

PMID- 15980684
TI  - Induction with abacavir/lamivudine/zidovudine plus efavirenz for 48 weeks
      followed by 48-week maintenance with abacavir/lamivudine/zidovudine alone in
      antiretroviral-naive HIV-1-infected patients.
AB  - BACKGROUND: The ESS40013 study tested 4-drug induction followed by 3-drug
      maintenance as initial antiretroviral therapy (ART) to reduce HIV RNA rapidly and
      then to simplify to an effective yet more convenient and tolerable regimen.
      METHODS: Four hundred forty-eight antiretroviral-naive adults were treated with
      abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) and efavirenz (EFV) for the 48-week
      induction phase. Two hundred eighty-two patients were randomized in a 1:1 ratio
      to continue ABC/3TC/ZDV+EFV or to simplify to ABC/3TC/ZDV for the 48-week
      maintenance phase. RESULTS: The baseline median HIV RNA level and CD4 cell count
      were 5.08 log10 copies/mL (56%>or=100,000 copies/mL) and 210 cells/mm (48% <200
      cells/mm), respectively. No significant differences were noted between
      ABC/3TC/ZDV+EFV and ABC/3TC/ZDV for an HIV RNA level <50 copies/mL (79% vs. 77%
      [intent to treat (ITT), missing=failure]; P=0.697) or time to treatment failure
      (P=0.75) at week 96. Drug-related adverse events were more commonly reported for
      ABC/3TC/ZDV+EFV than for ABC/3TC/ZDV (15% vs. 6%). Improvements in total
      cholesterol, low-density lipoprotein cholesterol, and triglycerides were observed
      in the ABC/3TC/ZDV group. Virologic failure occurred in 22 patients during
      induction and in 24 patients (16 in ABC/3TC/ZDV group and 8 in ABC/3TC/ZDV+EFV
      group; P=0.134) during maintenance. A greater proportion of patients receiving
      ABC/3TC/ZDV than ABC/3TC/ZDV+EFV reported perfect adherence at week 96 (88.8% vs.
      79.6%; P=0.057). CONCLUSIONS: After induction with ABC/3TC/ZDV+EFV,
      simplification to ABC/3TC/ZDV alone maintained virologic control and immunologic
      response, reduced fasting lipids and ART-associated adverse events, and improved
      adherence.

PMID- 15980685
TI  - Expression of chemokine receptors CCR5 and CXCR4 on CD4+ T cells and plasma
      chemokine levels during treatment of active tuberculosis in HIV-1-coinfected
      patients.
AB  - The pathogenesis of persistently elevated plasma HIV viremia in patients
      coinfected with tuberculosis (TB) during anti-TB treatment in Africans remains
      unknown. We examined the expression of chemokine receptors CCR5 and CXCR4 on CD4+
      T cells and plasma chemokine levels of macrophage inflammatory protein (MIP)
      1alpha, MIP-1beta, regulated on activation normal T expressed and secreted
      (RANTES), and stromal cell-derived factor (SDF)-1alpha among TB patients with HIV
      coinfection during the first 2 months of anti-TB treatment. During treatment of
      TB, the plasma HIV-1 load and CD4+ T-cell count remained unchanged. Levels of
      CCR5 and CXCR4 expression on CD4+ T cells as well as plasma levels of chemokines
      remained persistently elevated during anti-TB treatment. Persistently elevated
      plasma HIV viremia also paralleled persistently elevated expressions of activated
      CCR5+ or CXCR4+ CD4+ T cells. These results suggest that increased expression of
      CCR5 and CXCR4 on an activated CD4+ T-cell population coupled with persistently
      elevated chemokines may provide a suitable condition for continuous replication
      of HIV associated with TB coinfection. This, in turn, may contribute, at least in
      part, to the observed persistently elevated plasma HIV viremia in coinfected
      patients despite anti-TB treatment.

PMID- 15980686
TI  - Modeling long-term HIV dynamics and antiretroviral response: effects of drug
      potency, pharmacokinetics, adherence, and drug resistance.
AB  - We propose a long-term HIV-1 dynamic model by considering drug potency, drug
      exposure, and drug susceptibility. Using a Bayesian approach, HIV-1 dynamic
      parameters were estimated by fitting the model to viral load data from a phase
      1/2 randomized clinical study of 2 indinavir (IDV)/ritonavir (RTV)-containing
      highly active antiretroviral (ARV) therapy regimens in HIV-infected subjects who
      had previously failed protease inhibitor-containing ARV therapies. A large
      between-subject variation in estimated viral dynamic parameters was observed,
      even after accounting for variations in drug exposure and drug susceptibility,
      suggesting that characteristics of HIV-1 dynamics are host dependent. Significant
      correlations of baseline factors such as HIV-1 RNA levels and CD4 cell counts
      with viral dynamic parameters were found. These correlations coincide with
      biologic interaction mechanisms between HIV and the host immune system and also
      provide an explanation for the correlations between the baseline viral load and
      phase 1 viral decay rate, for which inconsistent results have been reported in
      the literature. The relations between viral dynamic parameters and virologic
      response were established, and these results suggest that viral dynamic
      parameters may play an important role in determining treatment success or
      failure. In particular, we estimated a drug efficacy threshold for each patient
      that can be used to assess whether an ARV regimen is potent enough to suppress
      HIV viruses in the individual patient. Our findings indicate that it is necessary
      to individualize the ARV regimen to treat HIV-1-infected patients. The proposed
      mathematic models and statistical techniques may provide a framework to simulate
      and predict antiviral response for individual patients.

PMID- 15980687
TI  - Response to highly active antiretroviral therapy at 6 months and long-term
      disease progression in HIV-1 infection.
AB  - OBJECTIVE: To compare the long-term prognostic significance of different
      definitions of immunologic and virologic responses to highly active
      antiretroviral therapy (HAART) at 6 months. METHODS: This was a prospective study
      conducted in 68 French hospitals. HAART was initiated in 2236 protease inhibitor
      naive patients included in the French Hospital Database on HIV. Multivariate Cox
      proportional hazard models measuring time from 6 months after starting HAART were
      used to compare the strength of the association between different definitions of
      immunologic and virologic responses at 6 months and subsequent progression to
      AIDS or death. The Akaike's Information Criteria were used to identify the most
      appropriate model. RESULTS: During a median follow-up of 58 months, 325 patients
      experienced an AIDS-defining event or died. The model that fitted best was the
      model in which the CD4 cell count and plasma HIV-1 RNA values attained at 6
      months were considered. The risk of clinical progression at 5 years ranged from
      7% (95% confidence interval [CI]: 4-10) in patients whose CD4 cell count at 6
      months was >or=350 cells/microL and whose HIV-1 RNA concentration was <3 log10
      copies/mL to 63% (95% CI: 52-75) in patients whose CD4 cell count at 6 months was
      <100 cells/microL and whose HIV-1 RNA concentration was >or=5 log10. CONCLUSIONS:
      Plasma HIV-1 RNA concentration and CD4 cell count should be taken into account
      independently when evaluating early response to treatment. The persistent impact
      of early response on clinical progression at 5 years emphasizes the major
      importance of the success of first-line HAART.

PMID- 15980688
TI  - Survival after cancer diagnosis in persons with AIDS.
AB  - The survival of persons with AIDS (PWA) has recently improved because of better
      antiretroviral therapies. Similarly, the prognosis of cancer has also improved.
      To determine if survival in PWA with cancer has also improved, we compared cancer
      survival in adults with and without AIDS using data from New York City from 1980
      through 2000. Analyses were made for AIDS-related cancers (Kaposi sarcoma, non
      Hodgkin lymphoma [NHL], and cervical cancer) and for 8 non-AIDS-related cancers
      (lung, larynx, colorectum, anus, Hodgkin lymphoma, breast, prostate, and testis).
      Death hazard ratios compared survival in PWA with cancer with that in cancer
      patients without AIDS, adjusted for age, sex, race, and calendar-time of cancer
      occurrence. The 24-month survival rate of PWA with cancer (9015 AIDS cancers and
      929 non-AIDS-related cancers of 8 types) improved significantly for most cancer
      types. By 1996 through 2000, the 24-month survival rate in PWA was 58% for Kaposi
      sarcoma, 41% for peripheral NHL, 29% for central nervous system NHL, and 64% for
      cervical cancer. For non-AIDS-related cancers, survival of PWA was lowest for
      lung cancer (10%) but was >50% for most other cancer types. In 1996 through 2000,
      significant differences in survival between cancer patients with and without AIDS
      still remained for Hodgkin lymphoma and lung, larynx, and prostate cancers. We
      conclude that recent improvements in AIDS and cancer care have greatly narrowed
      the gap in survival between cancer patients with and without AIDS. Clinicians
      should be encouraged by the improving prognosis and be diligent about detecting
      and treating cancer in PWA.

PMID- 15980689
TI  - Efficacy and tolerability of a nucleoside reverse transcriptase inhibitor-sparing
      combination of lopinavir/ritonavir and efavirenz in HIV-1-infected patients.
AB  - BACKGROUND: Recommended antiretroviral regimens include a nucleoside reverse
      transcriptase inhibitor (NRTI) component. Class cross-resistance and
      mitochondrial toxicity are recognized as problems with this class of
      antiretrovirals. METHODS: In a pilot open-label study, 65 antiretroviral-naive
      and 21 experienced but nonnucleoside reverse transcriptase inhibitor-naive HIV-1
      infected adults were given a combination of lopinavir/ritonavir (533.3/133.3 mg
      twice daily) and efavirenz (600 mg once daily) for 48 weeks. RESULTS: At
      baseline, the mean viral load was 4.84 log10 copies/mL and the mean CD4 count was
      311 cells/mm. At week 24, the proportions of patients with a viral load <400
      copies/mL were 78% and 93% using an intent-to-treat and on-treatment analysis,
      respectively. At week 48, proportions were 73% and 97%, respectively. Treatment
      discontinuation occurred in 21 patients during the 48-week period, with 33% of
      those attributable to drug-related adverse effects. A viral load >400 copies/mL
      at week 24 or 48 was associated with nonadherence in 3 patients and virologic
      failure in 1 patient. After an increase during the first 8 weeks, fasting lipid
      levels remained stable up to 48 weeks. CONCLUSION: The lopinavir/ritonavir
      efavirenz combination is associated with a high rate of virologic response and
      should be compared with more classic NRTI-containing regimens in randomized and
      controlled clinical trials.

PMID- 15980690
TI  - Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and
      pravastatin: results of AIDS Clinical Trials Group 5108 Study.
AB  - Efavirenz (EFV) is associated with hyperlipidemia when used in combination with
      other antiretroviral drugs. EFV is a mixed inducer/inhibitor of cytochrome P450
      (CYP) 3A4 isozyme and may interact with hydroxymethylglutaryl coenzyme A (HMG
      CoA) reductase inhibitors that are primarily metabolized via CYP3A4. To assess
      the drug-drug interaction of EFV used in combination with simvastatin (SIM),
      atorvastatin (ATR), or pravastatin (PRA), an open-label trial was conducted in 52
      healthy adult HIV-seronegative subjects across AIDS Clinical Trials Group sites
      in the United States. Subjects received 40 mg of SIM, 10 mg of ATR, or 40 mg of
      PRA daily on days 0 through 3 and days 15 through 18. EFV was administered daily
      at a dose of 600 mg on days 4 through 18. SIM, ATR, and PRA concentrations were
      determined before and after EFV, and EFV concentrations were determined before
      and after statins. EFV reduced SIM acid exposure (area under the curve at 0 to 24
      hours [AUC0-24 h]) by 58% (Wilcoxon signed rank test, P=0.003) and active HMG-CoA
      reductase inhibitory activity by 60% (P<0.001). EFV reduced ATR exposure by 43%
      (P<0.001) and the total active ATR exposure by 34% (P=0.005). EFV administration
      resulted in a 40% decrease in PRA exposure (P=0.005). SIM, ATR, and PRA had no
      effect on non-steady-state EFV concentrations. In conclusion, EFV, when
      administered with SIM, ATR, or PRA, can result in significant induction of statin
      metabolism. The reduced inhibition of HMG-CoA reductase activity during
      coadministration of EFV may result in diminished antilipid efficacy at usual
      doses of SIM, ATR, and PRA.

PMID- 15980692
TI  - An Italian approach to postmarketing monitoring: preliminary results from the
      SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) project on the
      safety of lopinavir/ritonavir.
AB  - The SCOLTA project (Surveillance Cohort Long-term Toxicity Antiretrovirals) is a
      system for online surveying of adverse reactions to recently commercialized
      antiretroviral drugs and a "sentinel" for unexpected and late adverse reactions
      arising during any antiretroviral treatment (available at:
      http://www.cisai.info). To date, 25 Italian departments of infectious diseases
      have participated at the project. The New Drugs Project is a prospective,
      multicenter, observational pharmacovigilance study involving 1 cohort of patients
      for each new drug. All patients who were consecutively started on lopinavir
      (LPV), tenofovir (TDF), peginterferon (IFN), atazanavir (ATZ), enfuvirtide (T
      20), and tipranavir (TPV) were enrolled. All grade III or IV adverse events
      (according to the AIDS Clinical Trials Group definitions) are reported on the web
      site. The Unexpected Events Project identifies unexpected adverse reactions
      during treatment and reports them. This paper presents the preliminary findings
      for the New Drugs Project. Between October 1, 2002, and March 30, 2004, 1184
      patients were enrolled. The lopinavir/ritonavir (LPV/r) cohort comprises 703
      patients, the TDF cohort 585, IFN 35, ATZ 95, T-20 10, and TPV 8. So far 100
      grades III and IV adverse events have been reported, 73 in the LPV/r group. In
      this cohort the rate of adverse events per 100 person-years was 14.2 on the basis
      of all patients treated, 9.8 for treatment-naive patients, and 15 for treatment
      experienced patients. These findings, though preliminary, show that this data
      collection method gives timely real-life information from which to assess the
      impact of short- and long-term toxicity of new antiretroviral drugs.

PMID- 15980691
TI  - Antiretroviral treatment simplification with 3 NRTIs or 2 NRTIs plus nevirapine
      in HIV-1-infected patients treated with successful first-line HAART.
AB  - OBJECTIVES: To assess the virologic noninferiority of an antiretroviral treatment
      simplification with coformulated zidovudine/lamivudine/abacavir (group 1) vs.
      coformulated zidovudine/lamivudine plus nevirapine (group 2) in HIV-1-infected
      patients receiving successful first-line highly active antiretroviral therapy.
      METHODS: This is a prospective, multicenter, open-label, comparative, randomized,
      noninferiority study. A delta of 15% for differences in virologic suppression
      <200 copies/mL between groups was prespecified with a 1-sided 0.025 significance
      level. RESULTS: A total of 134 patients were included into this study: 68 were
      allocated to group 1 and 66 to group 2. By intention-to-treat analysis (switch
      equals failure), the percentage of virologic suppression <200 copies/mL (<50
      copies/mL) at week 48 was 71.0% (65.1%) and 73.0% (63.3%) in groups 1 and 2,
      respectively (estimate for differences [<200 copies/mL]: -2.1, 95% CI: -17.4
      13.1, P=0.783). Thirteen and 14 patients in groups 1 and 2, respectively,
      discontinued therapy due to adverse events. Dyslipidemia improved in both groups,
      with a higher improvement in low-density lipoprotein cholesterol (P=0.049) in
      group 1. CONCLUSIONS: Group 1 is not inferior to group 2 regarding virologic
      suppression <200 copies/mL. Both strategies improve lipid profile.

PMID- 15980693
TI  - Causal pathways of the effects of age and the CCR5-Delta32, CCR2-64I, and SDF-1
      3'A alleles on AIDS development.
AB  - OBJECTIVE: To investigate the causal pathways by which age and the CCR5-Delta32,
      CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS. DESIGN: Analysis
      of follow-up data from 2 cohort studies among homosexual men (n=400), having >10
      years of follow-up. METHODS: The effects of the 4 cofactors on the CD4 and HIV-1
      RNA trajectories after seroconversion were modeled in a random-effects model. A
      proportional hazards model was used to investigate their effect on the risk of
      AIDS after correction for CD4 cell count and RNA level. This approach allows
      investigation as to whether they influence AIDS progression by affecting CD4
      count and RNA level or by other pathways. RESULTS: Persons of younger age or
      having the CCR2-64I or SDF-1 3'A mutation have significantly higher CD4 levels.
      Persons with the CCR5-Delta32 deletion or CCR2-64I mutation have significantly
      lower RNA levels. After correction for both CD4 count and RNA level, only the SDF
      1 3'A mutation significantly increases the AIDS risk. CONCLUSIONS: Age and the
      CCR5-Delta32 deletion and CCR2-64I mutation influence AIDS progression by
      affecting CD4 and HIV-1 RNA. The SDF-1 3'A allele increases the AIDS risk, but
      this effect is countered by its effect on CD4 and HIV-1 RNA level.

PMID- 15980694
TI  - Nonfinancial factors associated with decreased plasma viral load testing in
      Ontario, Canada.
AB  - OBJECTIVE: To examine whether individual characteristics were associated with
      differential use of viral load testing when testing is available without charge
      to all HIV-positive patients with provincial health insurance. METHODS:
      Individuals enrolled in the HIV Ontario Observational Database with complete
      medication records and health insurance numbers for linkage were studied.
      Generalized estimating equation regression models were used to examine the
      relationship between time-varying covariates such as plasma viral load levels,
      CD4 counts, and antiretroviral regimen characteristics and the number of days
      between viral load tests and the occurrence of an interval of >or=6 or 9 months
      between tests. RESULTS: A total of 1032 individuals were included in the analysis
      with a median follow-up of 4.6 years and a median of 18 viral load tests. In
      multivariate analyses, clinically important gaps in viral load testing were more
      likely among injection drug users (odds ratio [OR]=1.86, P<0.0001), in more
      recent years (P<0.01) and for individuals not using antiretrovirals (OR=1.70,
      P<0.0001) and less likely among individuals using >4 antiretrovirals (OR=0.62,
      P<0.0001). Results were similar when the outcome was the number of days between
      tests. CONCLUSIONS: Injection drug users, younger individuals, and residents of
      Toronto used fewer viral load tests than other individuals, even when financial
      barriers to testing were removed.

PMID- 15980695
TI  - The impact of incident and prevalent herpes simplex virus-2 infection on the
      incidence of HIV-1 infection among commercial sex workers in South Africa.
AB  - This study investigated the impact of prevalent and incident HSV-2 infection on
      the incidence of HIV-1 infection in a cohort of female commercial sex workers in
      KwaZulu-Natal, South Africa. Prior to a vaginal microbicide trial, 416 women were
      screened for antibodies to HIV-1 and herpes simplex virus-2 (HSV-2) infections
      and a questionnaire was used to establish behavioral, social, and demographic
      characteristics. A total of 187 HIV-1-seronegative women were followed up at
      monthly intervals when blood was drawn and used to detect HIV-1 and HSV-2
      antibodies. The median duration of follow-up was 2.2 years. At screening 50% of
      the women were HIV-1 seropositive and 84% were HSV-2 seropositive. The hazards of
      HIV-1 among women who were HSV-2 seropositive or seronegative throughout, or
      among those who seroconverted during the study, were not significantly different.
      When HSV-2 seroconversion was analyzed as a time-dependent covariate, the hazard
      ratio for HIV-1 seroconversion was 6.0 (95% CI: 2.6-14.0) times greater among
      women with incident than among women with prevalent HSV-2 infections. Drawing on
      other recent studies these data suggest that incident HSV-2 infection increases
      the risk of HIV-1 infection; the effect wanes with time since infection; and the
      effect is significantly greater for men than it is for women.

PMID- 15980696
TI  - HIV-inducing factor in cervicovaginal secretions is associated with bacterial
      vaginosis in HIV-1-infected women.
AB  - OBJECTIVE: Certain cervicovaginal lavage (CVL) fluid samples obtained from HIV-1
      infected and uninfected women stimulate in vitro HIV-1 replication. This
      activity, HIV-inducing factor (HIF), changes when CVL fluid is heated. We sought
      to confirm a previous observation that HIF was associated with bacterial
      vaginosis (BV). METHODS: HIF was measured in unheated and heated CVL fluid
      obtained from HIV-1-infected women and compared with the presence of BV by Nugent
      scores, other genital tract conditions, and cervicovaginal HIV-1 shedding.
      RESULTS: Among the 295 women studied, 54% of CVL samples had HIF activity and 21%
      showed heat-stable HIF activity. In adjusted logistic regression, heat-stable HIF
      was associated with BV (odds ratio [OR]=51.7, 95% confidence interval [CI]: 5.0,
      530.7) and with intermediate flora (OR=43.3, 95% CI: 3.6, 521.1); heat-labile HIF
      was not associated with BV. Neither heat-stable nor heat-labile HIF was
      associated with other cervicovaginal conditions nor, after controlling for plasma
      viral load, with genital tract HIV-1 shedding. CONCLUSION: We confirmed the
      association of HIF with BV and attribute it to the heat-stable component. Heat
      stable activity is also associated, although less strongly, with intermediate
      vaginal flora. We propose that heat-stable HIF is a result of products of BV
      associated bacteria.

PMID- 15980697
TI  - Safety, acceptability, and potential efficacy of a topical penile microbicide
      wipe.
AB  - Innovative, low-cost, and acceptable measures are needed to reduce sexually
      transmitted infections (STIs) including HIV. Use of a topical microbicide wipe
      for penile cleaning before and after sex might be effective in preventing STIs.
      However, evaluation of this simple method has not been done. Two studies were
      conducted in Malawi to determine the safety, acceptability, and potential
      efficacy of a benzalkonium chloride topical penile microbicide wipe. The first
      study was a phase 1 dose-escalating clinical trial among low-risk circumcised or
      uncircumcised HIV-negative men. The second study was a pilot before-after
      efficacy study among uncircumcised HIV-negative or -positive men. In the first
      study 24 circumcised and 27 uncircumcised men were enrolled. During the entire
      study period, 18 adverse events (AEs) were reported, and 3 AEs were confirmed by
      physical examination. Acceptability concerns did not increase with dose
      escalation, and adherence to use of the wipe ranged from 89%-95%. In the second
      study, 27 men were enrolled. Gram stain and culture tests showed significant
      reductions in frequency of several organisms after use of the wipe, including STI
      associated bacteria. This penile wipe is safe, acceptable, and can decrease the
      frequency of penile colonization with microorganisms. The clinical relevance
      remains to be determined in larger clinical trials.

PMID- 15980699
TI  - Motivations for participating in an HIV vaccine efficacy trial.
AB  - Understanding why people join HIV vaccine efficacy trials is critical for trial
      recruitment and education efforts. We assessed participants' motivations for
      joining the VaxGen VAX004 study, a randomized, double-blind, placebo-controlled,
      phase 3 multicenter trial. Of 5417 participants, 94% were men who have sex with
      men (MSM) and 6% were women at risk for heterosexual transmission of HIV. Most
      participants gave altruistic reasons for trial participation: 99% reported having
      joined to help find an HIV vaccine, and 98% reported having joined to help their
      community. Some gave more personal reasons: 56% joined to reduce risk behavior
      and 46% joined to get protection from HIV. Additional reasons related to
      receiving services or compensation included to obtain information about HIV
      (75%), to receive free HIV testing (34%), and for financial reimbursement (14%).
      Multivariate logistic regression analysis showed that female participants were
      significantly more motivated than male participants to join the trial for
      protection and to receive services or compensation (all P<0.05). Participants
      with 13 or more sex partners in the 6 months before enrollment were more likely
      than those with fewer sex partners to report having joined the trial for
      protection but less likely to have joined to reduce risk behavior (both P<0.05).
      Because many participants reported personal protection from HIV as their reason
      for joining, vaccine trial risk-reduction counseling should continue to emphasize
      the placebo-controlled trial design and unknown efficacy of the test product,
      particularly for women and persons with large numbers of sex partners. Because a
      significant minority of participants reported joining to receive HIV information,
      HIV testing, and financial reimbursement, a need is indicated for provision of
      HIV prevention services outside research trials and for monitoring to ensure that
      participants are not motivated to join trials for financial gain.

PMID- 15980698
TI  - HIV risk perception and prevalence in a program for prevention of mother-to-child
      HIV transmission: comparison of women who accept voluntary counseling and testing
      and those tested anonymously.
AB  - OBJECTIVE: To determine whether data from voluntary counseling and testing
      (VCT)/prevention of mother-to-child transmission (PMTCT) programs can be used for
      HIV surveillance. METHODS: Women attending an antenatal clinic at the district
      hospital in Entebbe, Uganda, from May 2002 to April 2003 were offered counseling
      and HIV testing with same-day results (VCT) and nevirapine for PMTCT was provided
      for HIV-positive women and their babies. Those who declined VCT were tested for
      HIV anonymously. RESULTS: Overall, 2635 women accepted VCT; 883 were tested
      anonymously. HIV prevalence was higher in VCT than in anonymously tested women in
      the first month of the program (20% vs. 11%, P=0.05) and in months with <70% VCT
      uptake (17% vs. 8%, P<0.001) but was similar in months with high uptake. Uptake
      of VCT was higher in women who had risk factors for HIV, especially those who
      believed themselves to have been exposed (84% vs. 73%, P<0.001). CONCLUSION:
      There was a bias to accepting VCT in women with HIV, or risk factors for HIV
      infection, the former most apparent when there was low coverage. Data from
      VCT/PMTCT programs cannot replace anonymous surveillance for monitoring of HIV
      epidemic trends where coverage is incomplete within clinics or communities.

PMID- 15980700
TI  - Methods to estimate the number of orphans as a result of AIDS and other causes in
      Sub-Saharan Africa.
AB  - OBJECTIVE: To derive methods to estimate and project the fraction of children
      orphaned by AIDS and other causes. METHODS: HIV/AIDS affects orphan numbers
      through increased adult and child mortality and reduced fertility of HIV-positive
      women. We extend an epidemiologic and demographic model used previously to
      estimate maternal orphans to paternal orphans. We account for the impact of
      HIV/AIDS on child survival by modeling the HIV status of the partners of men who
      die of AIDS or other causes based on data on the concordance of heterosexual
      partners. Subsequently, the proportion of orphans whose parents have both died is
      predicted by a regression model fitted to orphanhood data from 34 national
      demographic and health surveys (DHSs). The approach is illustrated with an
      application to Tanzania and compared with DHS estimates for the years 1992 and
      1999. RESULTS: Projections of the number and age distribution of orphans using
      these methods agree with survey data for Tanzania. They show the rise in
      orphanhood over the last decade that has resulted from the HIV epidemic.
      CONCLUSIONS: The methods allow estimation of the numbers of children whose
      mother, father, or both parents have died for countries with generalized
      heterosexual HIV epidemics. These methods have been used to produce orphan
      estimates for high-prevalence countries published by Joint United Nations Program
      on HIV/AIDS, World Health Organization, United Nations Children's Fund, and US
      Agency for International Development in 2002 and 2004.

PMID- 15980701
TI  - Epoetin alfa for treatment of anemia in HIV-infected patients.

PMID- 15980703
TI  - Do women with HIV infection have different indications for hysterectomy?

PMID- 15980705
TI  - Evaluation of periapical lesion healing by correction of gray values.

PMID- 15980706
TI  - Exploiting molecular methods to explore endodontic infections: Part 2--Redefining
      the endodontic microbiota.
AB  - The second part of this review discusses the application of molecular methods in
      endodontic microbiology research for a comprehensive characterization of the
      microbiota associated with different types of endodontic infections. Despite
      their recent introduction in endodontic research, molecular methods have already
      given a significant contribution to the understanding of endodontic infections
      and the future holds the perspective of a still better refinement of the
      knowledge about these infections. Molecular methods have revealed a higher
      complexity of the endodontic microbiota than previously reported by cultivation
      approaches. In addition to detecting some cultivable species in increased
      prevalence, molecular methods have also expanded the list of putative endodontic
      pathogens by inclusion of some fastidious bacterial species or even uncultivated
      bacteria that have never been previously found in endodontic infections.

PMID- 15980707
TI  - A prospective, randomized, double-blind comparison of bupivacaine and lidocaine
      for inferior alveolar nerve blocks.
AB  - The purpose of this prospective, randomized, double-blind study was to compare
      the degree of pulpal anesthesia obtained with 0.5% bupivacaine with 1:200,000
      epinephrine and 2% lidocaine with 1:100,000 epinephrine in inferior alveolar
      nerve blocks. Using a crossover design, inferior alveolar nerve blocks were
      randomly administered, in a double-blind manner, using 0.5% bupivacaine with
      1:200,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine, at two
      separate appointments, to 39 subjects. A pulp tester was used to test for
      anesthesia until two consecutive readings of less than 80 were recorded on at
      least three of the five experimental teeth. Anesthesia was considered successful
      when two consecutive 80 readings were obtained within 15 min and the 80 reading
      was continuously sustained for 60 min. Anesthetic success was significantly
      improved for all teeth except the first molar with the lidocaine solution. Pulpal
      anesthesia averaged 4 hr for bupivacaine versus 2 hr and 24 min for lidocaine.

PMID- 15980708
TI  - Pilot study of correlation of pulp stones with cardiovascular disease.
AB  - We propose that calcification of dental pulp may have a similar pathogenesis as
      calcified atheromas and could lead to use of routine dental radiographs as a
      rapid screening method for early identification of potential cardiovascular
      disease (CVD). Fifty-five dental patients ages 20 to 55 were chosen because pulp
      stones in pulpally noninflamed teeth were not expected in this age group. They
      completed a questionnaire regarding their CVD status and that of their parents
      and siblings. Entry criteria included at least one asymptomatic, minimally
      restored, noncarious molar and no history of gout, renal disease, or renal
      lithiasis. Patients' periapical radiographs of record were viewed to determine
      the presence of pulp stones. There was a significant relationship between pre
      existing CVD and pulp stones (odds ratio of 4.4 with a 95% confidence interval of
      1.1, 18.7), but no relationship was found for family history of CVD and pulp
      stones (odds ratio of 1.7 with a 95% confidence interval of 0.5, 5.5). Seventy
      four percent (14/19) of patients with reported CVD had detectable pulp stones
      while only 39% (14/36) of patients without a history of CVD had pulp stones. This
      pilot study demonstrates that patients with CVD have an increased incidence of
      pulp stones in teeth with noninflamed pulps compared to patients with no history
      of CVD. No relationship was found between presence of pulp stones and family
      history of CVD. The findings suggest that dental radiographic determination of
      the presence or absence of pulp stones may have possibilities for use in CVD
      screening.

PMID- 15980709
TI  - An evaluation of root ZX and elements diagnostic apex locators.
AB  - The purpose of this study was to compare the accuracy of the Root ZX and Elements
      Diagnostic electronic apex locators under clinical conditions. Thirty-six teeth
      planned for extraction were used. Each tooth was decoronated, coronally flared
      with Orifice Shapers, and irrigated with 2.6% sodium hypochlorite. Working
      lengths were measured with K-files using both electronic apex locators. The files
      were cemented at the last measured working length and the teeth were extracted.
      The apical 4-mm of each canal were exposed and photographed under 15x and 30x
      magnification. Images of each apex were projected and the distance from the file
      tip to the minor diameter was determined. The mean distances from the file tip to
      the minor diameter were 0.346 mm for the Elements Diagnostic and 0.410-mm for the
      Root ZX beyond the minor constriction. In locating the minor constriction the
      Root ZX was accurate 75% of the time to +/-0.5 mm, 83.3% +/-0.75 mm, and 88.9% to
      +/-1 mm. The Elements Diagnostic was accurate 75% of the time to +/-0.5 mm, 88.9%
      to +/-0.75 mm, and 91.7% to +/-1 mm. There was no statistically significant
      difference between the accuracy of the two electronic apex locators in locating
      the minor diameter (p < 0.05).

PMID- 15980710
TI  - The effect of antibiotics and endodontic antimicrobials on the polymerase chain
      reaction.
AB  - The effectiveness of endodontic antimicrobial treatment could be determined using
      sensitive molecular methods. The purpose of this study was to determine if
      antibiotics or endodontic reagents interfere with the ability of PCR to detect
      Enterococcus faecalis in vitro. Amoxicillin (25 mg/ml), clindamycin (15 mg/ml),
      tetracycline (25 mg/ml), doxycycline (10 mg/ml), calcium hydroxide, 1% buffered
      sodium hypochlorite (NaOCl1), 3% and 6% unbuffered NaOCl (NaOCl3 and NaOCl6), 2%
      chlorhexidine (CHX), 5% tincture iodine (TI), 2% iodine potassium iodide (IKI),
      chloroform (CF), 70% ethyl alcohol, 5% sodium thiosulphate, 5% citric acid or
      saline were added to 10 or 10 cells/ml E. faecalis ATCC 19433 for 1 h (1 wk for
      Ca(OH)2). Using PCR, all specimens were positive except for NaOCl3 and NaOCl6.
      PCR with Ca(OH)2 was positive with 10 cells/ml but negative with 10 cells/ml. The
      following reagents yielded negative culturing results: all antibiotics, Ca(OH)2,
      CHX, IKI, TI, NaOCl3, NaOCl6, and CF. BacLight nuclear staining revealed the
      presence of viable cells in all PCR positive, culture negative combinations,
      except for those with CF. Therefore, in the presence of threshold values of
      bacterial concentrations, all reagents tested except for NaOCl3 and NaOCl6 do not
      interfere with the detection of E. faecalis using PCR.

PMID- 15980711
TI  - Ultrastructural evaluation of the apical seal in roots filled with a
      polycaprolactone-based root canal filling material.
AB  - This in vitro study compared the ultrastructural quality of the apical seal
      achieved with Resilon/Epiphany and gutta-percha/AH Plus. Single-rooted extracted
      human teeth were prepared using a crown-down technique, debrided with NaOCl and
      EDTA, and obturated with either Resilon/Epiphany or gutta-percha/AH Plus. They
      were examined for gaps along canal walls using SEM, and for apical leakage using
      a transmission electron microscopy (TEM). SEM revealed both gap-free regions, and
      gap-containing regions in canals filled with both materials. TEM revealed the
      presence of silver deposits along the sealer-hybrid layer interface in
      Resilon/Epiphany, and between the sealer and gutta-percha in the controls. It is
      concluded that a complete hermetic apical seal cannot be achieved with either
      root filling materials.

PMID- 15980712
TI  - Comparison of the efficiency and effectiveness of various techniques for removal
      of fiber posts.
AB  - A study was conducted to determine the efficiency and effectiveness of several
      techniques for fiber post removal. Four groups of 20 mandibular premolars were
      endodontically treated and obturated. Post spaces were prepared for the following
      post systems: ParaPost XH, ParaPost Fiber White, Luscent Anchors, and Aestheti
      Plus. After cementation, 10 posts of each group were removed with their
      corresponding manufacturer's removal kit and the other 10 removed with diamond
      burs and ultrasonics. Removal times were recorded and the teeth were sectioned
      vertically and microscopically analyzed for removal effectiveness based on a 0 to
      5 point scale. Removal kits removed Luscent Anchors the fastest (mean = 3.9 min)
      and most effectively (mean = 2.6), while Aestheti-Plus posts were removed the
      slowest (mean = 7.3 min) and least effectively (mean = 3.4). Diamonds and
      ultrasonics required an average of 10 additional minutes for each fiber post
      system removal, yet removal effectiveness improved half a point. The results
      suggest recommended removal kits were significantly more efficient, while
      diamonds and ultrasonics were more effective. Removal kits could be enhanced with
      subsequent ultrasonic instrumentation to remove remaining fibers and cement.

PMID- 15980713
TI  - Bending fatigue study of nickel-titanium Gates Glidden drills.
AB  - ProFile nickel-titanium Gates Glidden drills were tested in bending fatigue to
      simulate clinical conditions. Ten samples each in sizes #1 through #6 were placed
      in a device that deflected the drill head 4 mm from the axis. The drill head was
      placed inside a ball bearing fixture, which allowed it to run free at 4000 rpm,
      and the total number of revolutions was recorded until failure. Fracture surfaces
      were examined with a scanning electron microscope to determine the initiation
      site and nature of the failure process. Mean +/- SD for the number of revolutions
      to failure for the drill sizes were: #1: 1826.3 +/- 542.5; #2: 5395.7 +/- 2581.5;
      #3: 694.4 +/- 516.8; #4: 261.0 +/- 138.0; #5: 49.6 +/- 14.9; #6: 195.9 +/- 78.5.
      All drills failed in a ductile mode, and fracture initiation sites appeared to be
      coincident with machining grooves or other flaws, suggesting the need for
      improved manufacturing procedures.

PMID- 15980714
TI  - The effect of thermocycling on a colored glass ionomer intracoronal barrier.
AB  - The purpose of this study was to evaluate the effect of thermocycling on a
      colored glass ionomer intracoronal barrier used for the prevention of
      microleakage. Thirty single canal premolars were decoronated, standardized in
      length, instrumented, obturated, and randomly assigned to three groups. Group 1
      received a 1 mm intracoronal barrier of Triage glass ionomer, group 2 received a
      2 mm Triage barrier, and group 3 received no barrier. After incubation for sealer
      set, teeth were thermocycled. Microleakage was measured using the fluid transport
      model. Groups 1, 2, and 3 demonstrated 1.68 mm, 0.60 mm, and 23.24 mm of
      movement, respectively. Using ANOVA and Student-Neumann-Keuls, group 3 leaked
      significantly more (p < 0.05) than groups 1 and 2, with no difference between
      groups 1 and 2. A 1 or 2 mm intracoronal barrier of Triage significantly reduced
      coronal microleakage in thermocycled endodontically treated teeth.

PMID- 15980715
TI  - Fracture strength of tooth roots following canal preparation by hand and rotary
      instrumentation.
AB  - The study aimed to determine fracture loads in tooth roots after canal
      preparation using different techniques. Mesiobuccal roots of 39 extracted
      mandibular molars were used. Three groups each of 13 roots were prepared by
      stainless steel hand files (K-files), and two rotary nickel-titanium techniques
      (Lightspeed and Greater Taper files). After obturation, a vertical load was
      applied by means of a spreader inserted into the canal until fracture occurred.
      The mean fracture load was 10.2 +/- 4.4 kg for K-files, 15.7 +/- 9.1 kg for
      Lightspeed and 13.2 +/- 6.1 kg for Greater Taper files, but differences were not
      statistically significant (p > 0.05). Most fracture lines were incomplete
      fractures on the buccal surface, followed by proximal and compound fractures.
      Greater apical enlargement (Lightspeed) or increased canal taper (Greater Taper
      files) did not increase fracture susceptibility of tooth roots.

PMID- 15980716
TI  - The effect of disruption of apical constriction on periapical extrusion.
AB  - The aim of this study was to compare the amount of apical extrusion during manual
      instrumentation and engine-driven rotary instrumentation in teeth with disrupted
      apical constriction. Fifty-two teeth were divided into two groups comprising 26
      teeth each. Teeth in each group were further divided into two sub-groups, the
      apices of which were enlarged approximately to a diameter of 0.2 mm and 0.4 mm.
      One group was instrumented using standardized technique with K-files and the
      other with ProFile .04 Taper Series 29, while irrigating with sodium
      hypochlorite. Glass vial model was modified for collection of extruded debris and
      irrigant as well as to integrate an electronic apex locator to the experimental
      assemble. The statistical analysis using Student's t test revealed no significant
      difference between instrumentation with K-files and ProFile .04 taper files (p >
      0.05). There was a tendency with both techniques to extrude apically more
      material as the diameter of the apical patency increased.

PMID- 15980717
TI  - Effects on smear layer and debris removal with varying volumes of 17% REDTA after
      rotary instrumentation.
AB  - The purpose of this study was to quantify the volume of 17% ethylene diamine
      tetra-acetic acid (EDTA) needed to efficiently remove the smear layer after
      rotary instrumentation, and to determine if additional irrigation has any effect
      on debris removal. Forty single canal teeth were instrumented with ProFile GT
      rotary instruments. Experimental groups were irrigated with 1, 3, or 10 ml of 17%
      EDTA for 1 min, followed by a final rinse with 3 ml of 5.25% sodium hypochlorite
      (NaOCl). Samples were scored for debris remaining and examined under SEM to
      determine quality of smear layer removal. There were no significant differences
      among groups when comparing either debris remaining or quality of smear layer
      removal. EDTA irrigation volume greater than 1 ml did not improve debris removal.
      Efficient removal of the smear layer was accomplished with a final rinse of 1 ml
      of 17% EDTA for 1 min, followed by 3 ml of 5.25% NaOCl.

PMID- 15980718
TI  - Root-end filling materials: apical microleakage and marginal adaptation.
AB  - The purpose of this study was to evaluate the root-end sealing ability through
      dye leakage evaluation and the marginal adaptation through scanning electron
      microscopy (SEM) of some root-end filling materials. Thirty human uniradicular
      teeth were used. Teeth were divided into three groups: (1) retrofilled with MTA
      Angelus, (2) with SuperEBA, and (3) with Vitremer. The root surfaces were
      isolated with nail polish and teeth were immersed in silver nitrate. Roots were
      sectioned transversally at each millimeter, in three sections and evaluated at a
      stereomicroscope to observe dye penetration. Using SEM the distance between the
      tested root-end filling materials and the surrounding dentin was measured at four
      points. The statistical analysis showed significant differences among the three
      materials in relation to the sealing ability (p < 0.05). Concerning marginal
      adaptation, MTA-Angelus presented the best results (p < 0.01). Absence of
      correlation between the two methodologies was clearly observed.

PMID- 15980719
TI  - Case difficulty assessment: the doorway to continuing education.

PMID- 15980720
TI  - Patient safety: the hallmark of nursing.

PMID- 15980724
TI  - To resolve or confront, that is the question.
AB  - Learn to address behavioral concerns in an efficient, proactive manner.

PMID- 15980725
TI  - Properly investigate harassment complaints.
AB  - Review the steps for investigating a harassment complaint.

PMID- 15980726
TI  - Monitor inpatient indicators to improve patient safety.
AB  - Revisions to JCAHO's Staffing Effectiveness Standard become effective July 1,
      2005.

PMID- 15980727
TI  - Error reporting as a preventive force.
AB  - IT advances make error reporting an instructive tool for improving patient
      safety. In the absence of national legislation and a national database, many
      states are breaking new ground in the patient safety movement, bolstered by the
      collection, interpretation, and dissemination of meaningful data.

PMID- 15980728
TI  - R&R triumph: 128 new nurses hired in 90 days.
AB  - A large Southeastern public health system developed recruitment strategies that
      reduced agency contract labor cost by millions.

PMID- 15980729
TI  - Best-practice protocols: every second counts.
AB  - The Institute for Healthcare Improvement seeks to partner with hospitals and
      healthcare organizations in a national initiative to implement protocols that
      prevent unnecessary patient deaths.

PMID- 15980731
TI  - Offer "safe passage" to patients.
AB  - Review key points and recommendations from Clarian Health's patient safety
      initiatives.

PMID- 15980732
TI  - Infection control: the fight to care and cure.
AB  - Effective infection control protocols hinge on staff training and certification.

PMID- 15980733
TI  - Profile of an admission nurse.
AB  - The staff of one Pennsylvania hospital revamps the admission by targeting health
      histories and ing a designated admission nurse.

PMID- 15980734
TI  - Smart pump implementation: one hospital's story.
AB  - Follow the process that managers from a South Carolina medical center used to
      select and implement smart infusion pumps.

PMID- 15980735
TI  - Resistant organisms necessitate total compliance.
AB  - A Midwestern academic medical center decreased healthcare-associated infections
      by implementing an aggressive campaign to increase hand hygiene compliance.

PMID- 15980737
TI  - Four steps toward easing disciplinary actions.
AB  - Deal effectively with disciplinary action through a four-step process.

PMID- 15980739
TI  - Tips for top challenges. Get a grip on behavior styles.

PMID- 15980740
TI  - [Targeted biotherapies in digestive oncology: a new era in therapeutic
      management?].

PMID- 15980741
TI  - Telebrix Gastro in the management of adhesive small bowel obstruction.
AB  - BACKGROUND: This study aimed to determine whether an abdominal radiograph 8 hours
      after ingesting oral Telebrix Gastro is a reliable marker for non-operative
      management in patients with adhesive small bowel obstruction. METHODS: During a 5
      year period (January 1, 1995, through December 31, 2000), 97 patients were
      admitted for small bowel occlusion due to adhesion with no indication for
      immediate surgery. All received 100 mL of Telebrix Gastro via gastric tube for
      small bowel obstruction due to adhesion. If the contrast reached the colon within
      8 hours on plain abdominal radiograph, the test was considered to be negative.
      RESULTS: 126 cases of small bowel occlusions were analyzed due to recurring
      episodes for 11 patients. The test was negative in 113 cases (89.7%), and in this
      group, only two patients underwent surgery, the remaining being managed non
      operatively. The 13 cases (10.3%) with a positive test for occlusion underwent
      surgery. The sensitivity, specificity and accuracy of the finding of contrast
      media reaching the colon as an indicator for conservative treatment were 98%,
      100%, and 98%, respectively. CONCLUSIONS: A water-soluble contrast study can be
      of significant help in the clinical management of patients suspected of having
      small bowel obstruction.

PMID- 15980742
TI  - Percutaneous endoscopic gastro-duodenostomy: modified technique.
AB  - OBJECTIVES: Percutaneous endoscopic gastro-jejunostomy is appropriate for
      patients with severe neurologic deficit to avoid repeated tube feeding-related
      aspiration. We describe a modified technique of endoscopic gastro-duodenostomy.
      PATIENTS AND METHODS: This technique was performed in 9 patients with severe
      neurologic deficit. No fluoroscopy was necessary. The gastrostomy button was
      pushed across the pylorus into the bulb; a nasogastric tube was then placed in
      the duodenum under endoscopic control and the button was drawn to the gastric
      wall. When the gastroduodenal tube migrated or was occluded, the button was
      placed in the bulb through the pylorus and maintained in this position for
      alimentation. RESULTS: Placement of the gastro-duodenostomy tube was successful
      without any complication in 100% of patients. The mean duration of the procedure
      was 15 min. The tube had to be removed for migration (N = 4) and occlusion (N =
      5) after a mean period of 5.8 weeks (range: 2-10). During the follow-up period,
      no tube feeding-related aspiration was observed. CONCLUSION: This modified low
      cost technique of endoscopic gastro-duodenostomy is simple and efficient.

PMID- 15980743
TI  - Mortality and morbidity after surgery of mid and low rectal cancer. Results of a
      French prospective multicentric study.
AB  - BACKGROUND: The aim of the study was to assess both mortality and morbidity
      following resection of mid and low rectal cancers in a French prospective
      multicentric study. PATIENTS: From June to September 2002, consecutive patients
      undergoing resection for cancer of the mid- or lower rectum were prospectively
      included in a multicentric study. Both postoperative mortality and morbidity were
      recorded. Multivariate statistical analysis was performed in order to assess risk
      factors predictive of postoperative morbidity. RESULTS: 238 patients with a mean
      age of 66 +/- 13 years (range: 26-88) were included. Neoadjuvant radiotherapy was
      performed in 68% of the patients. Total mesorectal excision was performed in 218
      patients (92%), of whom 151 (63%) had a sphincter saving procedure. Six patients
      died (2.5%). Overall postoperative morbidity rate was 43%, including anastomotic
      leakage (11%) and reoperation (5%). Mean hospital-in-stay was 20 +/- 16 days
      (range: 3191). Four independent risk factors of morbidity were found:
      perioperative fecal contamination (OR = 3.9 [1.1; 13.5]), mean operating time
      longer than 6 hours (OR = 4.5 [1.7; 12.1]), ASA score > 2 (OR = 3.2 [1.6; 7.9]),
      and smocking (OR = 3.3 [1.2; 8.9]). CONCLUSIONS: Resection of cancer involving
      the middle or lower rectum with sphincter saving procedures was possible in two
      thirds of the patients and was associated with 2.5% mortality and 43% morbidity.

PMID- 15980744
TI  - Endoscopic treatment of chronic pancreatitis.
AB  - OBJECTIVES: Endoscopy offers an alternative to surgery for the treatment of
      ductal complications in patients with chronic pancreatitis. The aim of this study
      was to evaluate the efficacy of endoscopic treatment on pain, cholestasis and
      pseudocysts in these patients. PATIENTS AND METHODS: Thirty-nine patients (37 M,
      2 F, mean age 44), were included in the study. All patients had at least one of
      the following criteria demonstrated by imaging tests: dilatation of the main
      pancreatic duct (MPD) with or without stricture (N = 13), bile duct stricture (N
      = 12), or pancreatic pseudocyst (N = 14) with pancreatic duct stricture (N = 11)
      or biliary stricture (N = 3). Pancreatic or biliary sphincterotomy, insertion of
      pancreatic or biliary stent, pseudocyst drainage with stent placement were
      performed according to ductal abnormalities. Patients were evaluated early and
      followed up during the stenting period, and after stent removal. RESULTS:
      Patients underwent a median of 3.5 endoscopic procedures with an interval of 2.2
      months between 2 stenting sessions. A pancreatic or biliary stent was inserted in
      25 patients with ductal abnormalities and in 11 patients with pseudocysts.
      Endoscopic pseudocyst drainage was performed in 6 cases. The mean stenting time
      was 6 months (range: 3-21). Mean follow-up after stent removal was 9.7 (2-48)
      months. Complications of endoscopic treatment were encountered in 7% of patients
      with no deaths. Pain relief was achieved after the first endoscopic procedure and
      during the overall stenting period in all patients. Recurrence of pain was
      observed after stent removal in 5/11 patients, requiring surgery in 4.
      Cholestasis decreased and biochemical values normalized within one month after
      biliary stenting. Recurrence of cholestasis was observed early after stent
      removal in 4/9 patients who required complementary surgical treatment. No
      recurrence of pancreatic pseudocyst was observed after endoscopic drainage and
      stent removal during the follow-up period. CONCLUSIONS: Endoscopic treatment of
      pain from pancreatic pseudocysts or ductal strictures is effective in the short
      term and in the period of ductal stenting. However, the optimal duration of the
      latter remains to be determined.

PMID- 15980745
TI  - [Gastrointestinal and liver disorders in athletes].

PMID- 15980746
TI  - [Recent data on the epidemiology of esophageal cancer].

PMID- 15980747
TI  - [Diagnosis and endoscopic treatments of superficial carcinomas of the esophagus].

PMID- 15980748
TI  - [Surgery of the esophageal cancer: for whom? How?].

PMID- 15980749
TI  - [Chemoradiation: an alternative to surgery for the curative treatment esophageal
      cancer?].

PMID- 15980750
TI  - [Palliative treatment of esophageal carcinoma: chemotherapy and palliative care].

PMID- 15980751
TI  - Treatment of fatigue in hepatogastroenterology: fact or fiction?

PMID- 15980752
TI  - [Non-HFE related hereditary iron overload].

PMID- 15980753
TI  - Gallbladder motility and gut hormone plasma levels in subjects with and without
      gallstones.
AB  - Hormonal control of gallbladder motility is still unclear in patients with
      cholelithiasis. In a case-control study, we determined the characteristics of
      gallbladder emptying evaluated sonographically and the hormone levels of
      somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal
      in 10 gallstone patients compared with 20 healthy subjects. Patients with
      lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a
      lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects.
      During fasting, plasma pancreatic polypeptide concentrations were significantly
      higher in lithiasis patients (P < 0.03). In contrast, no differences between the
      two groups of patients were observed during the post prandial period.
      Somatostatin and gastrin plasma levels were similar in the two groups. Lastly,
      the serum bile salt levels were in the normal range and were not different
      between groups both during fasting and postprandial states. We conclude that
      large basal plasma concentrations of pancreatic polypeptide, a gut peptide
      inducing gallbladder relaxation, may constitute a factor facilitating
      lithogenesis.

PMID- 15980755
TI  - [Indications for liver transplantation. Text of recommendations - long version].

PMID- 15980754
TI  - Usefulness of specific IgG avidity for diagnosis of hepatitis A infection.
AB  - AIM: Diagnosis of acute hepatitis A virus (HAV) infection is classically based on
      the detection of HAV-IgM. Nevertheless, HAV-IgM can be positive for patients with
      polyclonal stimulation of their immune system (i.e. immune reactivation). To
      improve the diagnostic yield, an avidity test for HAV-IgG antibodies was
      developed and tested. METHODS: Avidity tests were performed in 128 sera: 11
      selected samples from patients with past infection, 15 acute hepatitis A, 10
      vaccinated subjects and 4 patients with immune reactivation as well as 84 HAV-IgM
      positive unselected sera, provided by routine laboratories. RESULTS: Patients
      with past infection had avidities over 70%, whereas avidities in patients with
      acute hepatitis A were below 50% during the first month following the onset of
      symptoms. As expected, patients with immune reactivation had avidities over 70%
      consistent with past infection. The results obtained for the 84 unselected sera
      allowed reconsidering the diagnosis of acute hepatitis A for nearly a third of
      patients. CONCLUSION: This test could improve the diagnosis of acute hepatitis A
      infection, particularly in elderly patients.

PMID- 15980756
TI  - [Indications for liver transplantation. Text of recommendations - short version].

PMID- 15980757
TI  - Abnormal appearance of the internal anal sphincter at ultrasound: a specific
      feature of progressive systemic sclerosis?
AB  - Endosonography is now an effective tool for the assessment of anorectal
      pathologies. We present a case of rectal prolapse in a patient with progressive
      systemic sclerosis, with low resting anal pressure, no rectoanal inhibitory
      reflex in manometry, and a thin, heterogeneous, difficult to delineate, internal
      sphincter on endoanal ultrasound. We also provide a review of the literature on
      anorectal involvement in progressive systemic sclerosis.

PMID- 15980758
TI  - Azathioprine induced nodular regenerative hyperplasia in IBD patients.
AB  - Purine analogues are major drugs in the treatment of inflammatory bowel diseases
      (IBD). We present four cases of nodular regenerative hyperplasia of the liver
      (NRH) developed in patients with IBD treated with azathioprine. All patients had
      either abnormal liver tests and/or low platelet count. Although biochemical and
      hematological abnormalities regressed after azathioprine withdrawal, the long
      term evolution of the hepatic lesions (and the risk to develop further
      complications including portal hypertension) remains to be determined. Male
      gender seems to be a major risk factor by providing a predisposing
      pharmacogenetic profile of purine analogue metabolism. Clinicians should be aware
      of this serious complication which may occur with any of the purine analogues
      (azathioprine, 6-mercaptopurine, and 6-thioguanine).

PMID- 15980759
TI  - [Spontaneous rupture of the spleen in chronic calcifying pancreatitis: report of
      three cases].
AB  - Spontaneous rupture of the spleen is a rare complication of chronic calcifying
      pancreatitis. Anemia and hemorrhagic shock may not occur, making diagnosis more
      difficult. Favourable response to conservative treatment does not prevent the
      need for splenectomy, as calcifiying chronic pancreatitis may progress locally.
      We report three cases of spontaneous rupture of the spleen. In two cases, splenic
      rupture revealed calcifying chronic pancreatitis and both patients underwent
      urgent splenectomy. In the third case, the patient was known to have calcifying
      chronic pancreatitis, and splenectomy was performed because of unsuccessful
      conservative treatment. We discuss the role of distal pancreatectomy during
      splenectomy to reduce the rate of postoperative complications and additional
      surgery. We also discuss the role of arterial embolisation and laparoscopy in the
      management of this rare condition.

PMID- 15980760
TI  - [Echoendoscopic ultrasound/fine needle aspiration of an hepatic cystadenoma].
AB  - The diagnosis of hepatic cystadenoma is difficult with the conventional
      radiologic imaging. When these hepatobiliary cystic tumors are located in the
      left liver, Echoendoscopic ultrasound/Fine needle aspiration can help in the
      diagnosis by showing high levels of cystic CEA and CA 19-9 in a mucinous fluid.
      Definitive histological evaluation is assessed by the examination of the
      operative specimen.

PMID- 15980761
TI  - [Prevalence of Helicobacter pylori infection in Corsica].

PMID- 15980762
TI  - [Endoscopic treatment of oesophageal fistulae with glue injections
      (cyanoacrylate, Histoacryl].

PMID- 15980763
TI  - [Poorly differentiated endocrine carcinoma and adenocarcinoma on Barrett's
      esophagus].

PMID- 15980764
TI  - [Quality control in digestive endoscopy].

PMID- 15980765
TI  - [Use of the FISH technique to identify the origin of an endocrine carcinoma in a
      liver graft].

PMID- 15980767
TI  - [Optical coherence computed tomography in gastroenterology].

PMID- 15980766
TI  - [Ischemic anterior optic neuropathy complicating interferon alpha-2a and
      ribavirin treatment for acute hepatitis C].

PMID- 15980768
TI  - [Consensus conference on pregnancy and smoking, 7-8 October 2004, Lille, France].

PMID- 15980770
TI  - Consensus conference on pregnancy and smoking, 7-8 October 2004, Lille, France.
      (text of guidelines, short version).

PMID- 15980771
TI  - [Consensus conference on pregnancy and smoking, 7-8 October 2004, Lille, France.
      (text of guidelines, long version)].

PMID- 15980772
TI  - [Smoking (active or passive) in relation to fertility, medically assisted
      procreation and pregnancy].
AB  - Maternal and paternal smoking are associated with numerous problems of
      reproduction and pregnancy. Among men, active smoking reduces the quality and
      mobility of the spermatozoa which could result in loss of fertility. It also
      increases the risk of impotence. Moreover, active smoking of the father is
      responsible for passive smoking for the mother and her baby. Among women, active
      smoking has a negative impact on fertility and in case of treatments against
      infertility, the chances of success are reduced. It leads to delayed conception
      and increases the risk of ectopic pregnancies and placental complications. It
      reduces the risk of pre-eclampsia but it also worsens its consequences. Passive
      smoking has not been associated with certainty with any clear impact on fertility
      among men and women. By contrast, active and passive smoking can lead to intra
      uterine growth retardation and a lower birth weight.

PMID- 15980773
TI  - [What are the epidemiological data on smoking and co-addictions during
      pregnancy?].
AB  - The goal of this publication is to attempt to better understand how we arrived at
      this medical catastrophe: 28% of the French women who smoke during the pregnancy!
      And that does not take into account other addictions (alcohol, drugs legal or
      illegal) whose figures are poorly specified. From the American epidemiologic
      data, the United States being ahead of us in the stage of the epidemic, and
      European data, can one extract the favoring factors and effective measurements to
      stop this epidemic? What is the epidemiology of the other addictions and is there
      any relationship between the consumption of tobacco and other drugs? According to
      the world statistical data, less than 50% of pregnant women manage to stop
      smoking. In the United States, 44.3% of the women are able to stop the gravidic
      nicotine addiction in comparison with 83.1% who stop alcohol and 68% illegal
      drugs, which places tobacco as the leading hard drug. The best prevention is thus
      to try to convince young people not to start. What is the situation on this
      point?

PMID- 15980774
TI  - [What are the epidemiological data concerning parental smoking and
      breastfeeding?].
AB  - Exclusive breastfeeding for 6 months provides important protection against
      respiratory infections in the newborn's first year of life. But smoking by either
      parent not only creates excess risk of respiratory illness for the baby, it also
      plays an important role both in not breastfeeding or in early weaning, thus
      depriving the infant of the potential protections of receiving mother's milk.
      Considering this information, three main recommendations can be made: promoting
      smoking cessation by the mother and also by the father may be a key to successful
      efforts to encourage breastfeeding; a smoking mother can enhance her chances of
      successful breastfeeding by avoiding smoking at least 2(1/2) hours prior to each
      feeding; a smoking father can enhance breastfeeding by avoiding exposing the
      mother as much as he should avoid exposing the infant to tobacco smoke.

PMID- 15980775
TI  - [Periodontal diseases, tobacco and pregnancy].
AB  - This review summarizes the impact of tobacco on the periodontium of pregnant
      women and the effects of periodontal diseases combined with tobacco on the
      pregnancy. Periodontal diseases (gingivitis and periodontitis) are gram-negative
      anaerobic infections. Smokers are 2-7 times more likely to develop periodontal
      disease than non-smokers. Tobacco, an environmental factor, undermines the host
      response and may facilitate the development and progression of periodontal
      disease. Recent epidemiological studies suggest that maternal periodontal
      diseases would be a risk factor of pre-term deliveries or pre-term low birth
      weight (PLBW). Cigarette smoking during pregnancy leads to peri-natal morbidity
      and mortality and it is associated with reduced birth-weight. Tobacco during
      pregnancy also amplifies the risk of PLBW directly and via periodontal diseases.
      This article highlights the etio-pathogenic interrelations between periodontal
      diseases and tobacco as risk factors of PLBW. The blood dissemination of
      periodontal bacteria and the effects of cytokines like TNF-alpha, Il-1, produced
      during periodontal infections could explain these obstetrical adverse events. The
      concept of diagnosing and treating a periodontal disease in a pregnant woman to
      minimizes the deleterious effects of this infection on systemic conditions
      represents an unprecedented challenge. Moreover, periodontist have the
      opportunity to take part in smoking cessation program for pregnant women.

PMID- 15980776
TI  - [What are the epidemiological data on the consequences of smoking-related
      increased risk in pregnant women? Dermatological consequences].
AB  - Smoking has numerous effects on skin. Some of them are well established, others
      are more debatable. Smoking is a cofactor of skin aging after chronic sun
      exposure, as demonstrated by recent histological, biochemical and cutaneous
      relief studies. Smoking is a well established risk factor of cutaneous, mucous
      membrane cancers, and some gynecologic cancers as well, in some cases increased
      by pregnancy. However, published studies have included small numbers of subjects.
      Some skin affections are worsened by smoking, and others might be improved.
      However scientific data on smoking and skin or pregnancy are both scarce.

PMID- 15980777
TI  - [Maternal and paternal smoking: risk excess to tobacco smoking in pregnant
      women].
AB  - Active and passive smoking is a health risk and its toxicity during pregnancy is
      well known; nevertheless, in France, nearly 30% of pregnant women smoke. The aim
      of this study is to describe the toxic effects of smoking during pregnancy by a
      review of the international literature. At the outcome of this study, it appears
      that besides the well known effects of smoking on pregnancy, foetal development
      and state of health of the mother and child, other effects may be encountered
      such as neuropsychiatric, infections, endocrine, metabolic and cardiorespiratory
      events. While complementary studies are necessary to define the nature of the
      relationship between the observed effects and smoking, this study underlines the
      fact that the reduction of prevalence of smoking in pregnant women is a major
      health issue.

PMID- 15980778
TI  - [Consequences of cigarette smoking on male fertility].
AB  - The different studies conducted over the last fifteen years on the consequences
      of cigarette smoking on male fertility have shown a decrease of sperm quality in
      smokers. In fact, the components of cigarette smoke pass through the blood-testis
      barrier and thus induce an alteration of sperm parameters and nucleus quality of
      the spermatozoa. Beyond this decrease of sperm quality, cigarette smoking also
      appears to have an impact on the smoker's offspring: lower embryo quality,
      increased risks to develop a childhood cancer. The pathophysiologic mechanisms
      are not yet clearly understood, but one of the most likely hypotheses is the
      production of an oxidative stress which is responsible for DNA fragmentation
      compromising the chances of pregnancy. In addition to the spermogram, further
      tests available in specialized laboratories can be prescribed to evaluate
      spermatozoal DNA fragmentation (TUNEL Assay, SCSA...). Antioxidant treatment can
      be administrated to reduce DNA fragmentation and increase the chances of
      pregnancy.

PMID- 15980779
TI  - [Consequences on women's fecundity and on assisted reproductive technology].
AB  - Knowledge of the detrimental role of cigarette smoking on human reproduction is
      constantly improving. In natural fertility, time to pregnancy is longer,
      frequency of infertility is increased and fertility rate declines 10% to 20% with
      a dose-effect relationship. Moreover, women exposed in utero also have lower
      fertility. Cigarette smoking is also a risk factor for menstrual disorders and
      for early menopause. In assisted reproductive technology, where many parameters
      are controlled, the deleterious effects of smoking on fertility have been clearly
      demonstrated: lower estradiol levels, decreased pregnancy and implantation rates,
      and poorer oocyte morphology. The two published meta-analyses have concluded that
      the effects are the same in natural and assisted reproduction. These results are
      in accordance with biological hypotheses on the local and general effect of
      tobacco and other cigarettes components. In conclusion, women should be informed
      about the effect of cigarette smoking on their fertility. Education is very
      important since in many countries, like France, the percentage of smokers is
      increasing among women, especially among young women.

PMID- 15980780
TI  - [Smoking and ectopic pregnancy: is there a causal relationship?].
AB  - Tobacco smoking is often studied as a risk factor in epidemiology. The impact on
      fertility and pregnancy is significant. At conception, maternal smoking may have
      an effect on the occurrence of ectopic pregnancy. Experimental studies on
      hamsters show interactions between tobacco and the oviduct. These interactions
      may explain the role of tobacco in ectopic pregnancy. Eleven case-control studies
      compared smoking in two groups of women: a cases group with ectopic pregnancy,
      and a control group. Ten of them found a relationship between tobacco smoking and
      ectopic pregnancy (increased relative risk). Considering this results, we must
      encourage women to reduce or better to stop smoking.

PMID- 15980781
TI  - [Maternal cigarette smoking during pregnancy and malformations].
AB  - While cigarette smoking continues to increase among women, the influence of
      maternal smoking during pregnancy on the prevalence of malformations has been
      widely investigated over the past 30 years. Although many women discontinue
      smoking during pregnancy, the fetus is still often exposed during first weeks of
      gestation, including embryological development, raising questions about the
      teratogenic effect of smoking. We review the literature on this topic
      highlighting methodological issues. The overall prevalence of malformations does
      not seem to be increased among offspring of women who smoked during pregnancy. A
      mild but significant association was found between several specific malformations
      (oral cleft, gastroschisis and craniosynostosis) and maternal smoking. Though the
      odds ratios were very low for these associations, the change in absolute number,
      especially for facial clefts, is important due to high prevalence of smoking
      during pregnancy. These findings should be taken into account in preconceptional
      counselling.

PMID- 15980782
TI  - [Smoking and pregnancy complications].
AB  - Because of changing trends in feminine behavior concerning smoking and pregnancy,
      we must seriously modify our objectives of prevention. The deleterious risks
      attributable to smoking in pregnant woman are well known. Abruptio placentae is
      one of the most devastating. It is also known that the risk falls rapidly with
      abstinence from smoking. So why so much silence on the topic? Why so little
      interest in motivating our patients to stop smoking while other efforts in
      gynecology-obstetrics have met with success? The objective could be to imitate
      our Swedish colleagues. In 1983, 31% of Swedish women smoked daily in the
      beginning of pregnancy, in 1997 not more than 16%.

PMID- 15980783
TI  - [Consequences of smoking on fetal development and risk of intra-uterine growth
      retardation or in utero fetal death].
AB  - Active and passive smoking constitutes one of the most serious public health
      problems due to the deleterious effect on the expected infant and the mother.
      These effects are dose dependent as illustrated by intra-uterine growth
      retardation, where the effect worsens with duration of smoking during pregnancy,
      and also by other conditions such as abrutio placentae or placenta praevia,
      premature rupture of the membranes and preterm birth, where the risk is
      multiplied by two (or even three)! In utero death is the ultimate sanction.
      Studies on the consequences of maternal smoking on fetal development have
      demonstrated the cardiovascular effect (CO and nicotine) and the respiratory
      effect (CO) which can be aggravated after birth by passive smoking. Teratogenic
      and cancerogenic effects have also been clearly demonstrated. Maternal smoking
      would also affect fetal brain development with negative effects on the major
      neurotransmitter systems (domaminergic, serotinergic, noradrenergic) and on the
      development of key structures such as the prefrontal cortex, certain limbic
      structures including the hippocampus and other structures implicated in motor
      function such as the ventral striatum. These development anomalies of the brain
      could give rise, after birth, to psychological, behavioral, attention and
      cognitive disorders, further arguments in favor of an effective anti-smoking
      policy including appropriate care for smoking pregnant mothers in both hospital
      and outpatient settings.

PMID- 15980784
TI  - [Effect of smoking on mode of delivery and per partum hypoxia and acidosis].
AB  - METHODS: We conducted a PubMed research using the following key words: fetal,
      smoking, distress, hypoxia, acidosis, heart rate, cesarean. RESULTS: The
      different combinations of key works allowed selection of 251 since 1967. Several
      article were addressed directly to the question raised; two for meconial fluid
      alone. One article detailed possible method biases. Several articles detailed the
      Apgar score in newborns of smoking mothers. Three calculated the risk of cesarean
      section in smokers. CONCLUSION: Data in the literature is not sufficient to argue
      in favor of an association between fetal asphyxia during labor and smoking. Only
      one study showed a higher rate of cesarean section in mothers smoking more than
      10 cigarettes per day. Nevertheless, the Apgar score does not appear to be
      modified by moderate maternal smoking. Paradoxically, maternal smoking could have
      a protective effect on meconial aspiration and could have a moderately reducing
      effect on the rate of cesarean section during labor in patients smoking less than
      10 cigarettes per day via lower fetal weight. These findings should be examined
      with caution because they still need to be confirmed and do not take into
      consideration other adverse effects of smoking on the fetus.

PMID- 15980785
TI  - [What are the markers of tobacco smoking?].
AB  - In this updated review of tobacco smoking markers (smokers non-smokers) in
      various biological environments, during varied circumstances of use, we present
      the parameters known to be detectable to date. The focus is placed on:--certain
      bio-markers used in routine practice: plasmatic, urinary or salivary cotinine end
      expired carbon monoxide,--certain minor tobacco alkaloids such as anabasine and
      anatabine, as potential bio-markers, particularly for monitoring abstinence
      during nicotinic substitution therapy,-- use of superficial body growths (hair
      and nails) as a biological environment for measuring nicotine and cotinine to
      monitor exposure to environmental tobacco smoke and fetal exposure.

PMID- 15980786
TI  - [How should markers of smoking be used during pregnancy?].
AB  - Consultation or hospitalization for pregnancy, irrespective of the patient's
      motivation, is always an exceptional opportunity for coupling care for the
      smoking addiction with antenatal surveillance. In studies on markers of smoking
      addiction during pregnancy, the most used markers are expired carbon monoxide
      (CO) and urinary cotinine. Expired CO can be used to estimate the level of active
      or passive smoking and thus enable the mother to realize the risks for her baby
      and appreciate how easy it is to decrease these risks. In the future, the quality
      of perinatal care will depend greatly on improved management of smoking mothers
      with the objective of reducing fetal exposure. An insufficient amount of work has
      been done on evaluating the contribution of markers of smoking during pregnancy
      or feeding. Improvement requires better awareness of perinatal healthcare
      professionals, measurement of expired CO during pregnancy, implementation of
      validated medicinal and/or cognitivobehavioral methods, and clearly stated
      support from political and administrative authorities.

PMID- 15980787
TI  - [What smoking cessation interventions are effective in pregnant women?].
AB  - Tobacco smoking during pregnancy is the single largest modifiable risk for
      pregnancy-related morbidity and mortality. Tobacco smoke contains thousands of
      chemicals, many of which may contribute to reproductive toxicity. Carbon monoxide
      is the most biologically significant toxin for the fetus. The use of nicotine
      replacement therapy is probably not without risk, although the magnitude of risk
      to the mother and fetus is much lower than continuing smoking. Most pregnant
      women are motivated to stop. It is, therefore, a good time to initiate smoking
      cessation as early as possible during pregnancy, and to maintain abstinence
      during post-partum to protect the infant from passive smoking. If behavioral
      intervention fail to produce abstinence, a sign of high dependence, nicotine
      replacement therapy should be initiated promptly. Although bupropion is not
      recommended during pregnancy, this therapy should be considered when
      contraindications are carefully observed. It is recommended that all patients
      treated with nicotine or bupropion be reported to a pregnancy registry that
      collects pregnancy and obstetrical outcome data. This registry would allow health
      professionals to share their experience and should encourage them to use
      pharmacotherapy more frequently and lift psychological barriers concerning its
      use in pregnant women.

PMID- 15980788
TI  - [Cessation of smoking: implementation of effective techniques. Prenatal and
      hospital pregnancy consultations with smoking women and/or smoking couples].
AB  - Smoking during pregnancy is a public health problem. Throughout this period,
      cessation is crucial. Everybody agrees that pregnancy is an appropriate moment to
      try to quit. Continuing smoking is a major risk for both the pregnant woman and
      her baby to come. Tobacco contains numerous toxics which easily pass through the
      placenta. All healthcare teams should be committed to helping pregnant women stop
      smoking and should train themselves to provide advice and support. The healthcare
      structures should implement consensual preventive and curative actions. Many
      diagnostic and curative tools are available for global care of pregnant smoking
      women. Their partners, whether smokers or not, should play a preponderant role.
      In addition to psychological support, it is important to note that nicotinic
      substitutes are indispensable tools for helping dependent pregnant women stop
      smoking.

PMID- 15980789
TI  - [Use of tobacco cessation tools for pregnant women or couples attending pre-birth
      counseling sessions].
AB  - Several tools have been helped to patients cease smoking. Many are poorly known
      and thus used little. In the context of pregnancy, midwives conducting pre-birth
      counseling sessions can help pregnant women and their partners stop smoking. The
      terms used during the sessions offer many occasions.

PMID- 15980790
TI  - [Smoking and breastfeeding: how can we help mothers stop smoking?].
AB  - The study of nicotine metabolism shows that nicotine has a half-life of 60 to 90
      min, and that nicotine concentration in human breast milk is 2.9 times higher
      than in the plasma. Smokers are less likely to choose breastfeeding. The duration
      of breastfeeding is shorter and there is less milk production amongst smokers who
      decide to breastfeed. Breastfeeding diminishes the infant's respiratory problems
      that are linked to smoking. During the breastfeeding period, in addition to
      psychological support, nicotine replacement therapy should be proposed,
      preferring gums or 2 mg tablets with a short half-life taken after feeding. For
      those who continue to smoke, the number of cigarettes should be limited and
      smoking should be done after feeding and outside of living quarters.

PMID- 15980791
TI  - [Neonatal consequences of maternal smoking during pregnancy].
AB  - In utero tobacco consumption is a serious public health problem in France; it is
      very frequent and the long term consequences are not only numerous but also
      misinterpreted by our population. 25 to 29% of women arrive at the end of their
      pregnancy without stopping smoking and 50% of non smoking mothers live in an
      environment polluted by tobacco during pregnancy. The authors would like to
      stress the gravity of this situation. At the maternity hospital in Nimes, 358
      women who gave birth at term and after a normal pregnancy were enrolled in a
      survey and monitored with thiocyanate for their tobacco consumption. Birth
      weight, height, and cranial perimeter of the infants were noted at birth. Results
      confirmed earlier work on this subject: the three variables studied were
      consistently weakened by the mother's addiction to tobacco. The authors recall
      previous medical literature on the pathophysiology and other consequences on the
      brain: such as I.Q. behavior, sudden infant death syndrome, vascular alterations
      with possible long-term complications, as well as pulmonary alterations on which
      there has recently been much research. The question is raised as to why this
      problem is so neglected in our society and what could be done to change this
      state of affairs.

PMID- 15980792
TI  - [Relationship between sudden infant death and in utero exposure to smoking: how
      should smoking parents be informed?].
AB  - Recent campaigns on having infants sleep on their back has decreased the rate of
      sudden infant death. Other risk factors have also been identified, including
      maternal smoking during pregnancy. While many studies have methodological biases,
      most demonstrate a two to three-fold increase in the risk of sudden infant death
      among mothers who smoked during pregnancy. The effect of smoking is basically
      caused by nicotine which is toxic for the brain. This compound has specific
      trophicity for the respiratory centers rich in nicotinic cholinergic receptors.
      Deficiencies which could result could lead to greater vulnerability of the infant
      to episodes of hypoxia. The risk would be dose dependent and more marked in women
      smoking more than nine cigarettes per day. After birth, certain factors would
      increase the risk, including passive smoking and sleeping in the mother's bed.

PMID- 15980793
TI  - [Effects of maternal smoking during pregnancy on fetal brain development].
AB  - Tobacco during pregnancy remains a health priority. It is associated with an
      increased risk of preterm birth and intra-uterine growth retardation which are
      well-known risk factors of diplegia or cognitive sequellae. Several studies
      support the existence of an association between smoking in pregnancy and a less
      optimal cognitive development. However this point has not been confirmed in a few
      recent studies, in particular when confounding factors are taken into account.
      Behavioral disorders are significantly associated with smoking during pregnancy.
      Nicotine was the best studied component of tobacco in animal studies. It was show
      that it interferes directly by stimulation of neurotransmitters or indirectly by
      inducing brain hypoxia.

PMID- 15980794
TI  - [What are the other long-term consequences of maternal smoking during
      pregnancy?].
AB  - Maternal smoking during pregnancy has many consequences on the fetus, and later
      on the child. Excluding the increase in sudden infant death and psychomotor and
      cognitive development disorders, we focus here on other problems. Precocious
      adverse disturbance of lung function favor respiratory tract infections and
      asthma. Growth is impaired, principally an increased risk of obesity. Certain
      endocrine functions (thyroid, gonad and also pancreas) seem to be dysregulated.
      Fears exist about hemodynamic consequences. Maternal smoking during pregnancy is
      a public health problem for the offspring, and the risk is more likely if
      exposure persists after birth.

PMID- 15980795
TI  - [Smoking and anesthesia].
AB  - There is no specific study about consequences of smoking in anesthetized pregnant
      women. General anesthesia is mainly involved in adverse effects of smoking. Among
      smoking patients, there is a significant increase in the incidence of cardiac and
      respiratory complications during and after anaesthesia. Post operative anxiety
      increases in smokers patients. But smoking decreases the incidence of nausea and
      vomiting after surgery. It would be better if smoking cessation took place 2
      months before surgery, it is necessary to stop smoking 12 hours before
      anaesthesia. For general anaesthesia, propofol and sevoflurane provide less
      respiratory complications than other drugs. If possible, regional anaesthesia is
      the best choice for smoking patients.

PMID- 15980796
TI  - [Obstetrical perinatal care in case of maternal prenatal smoking].
AB  - Measurement of CO during the intrapartum period is a good way to help patients
      become aware of the importance of smoking cessation. The objective information
      can be continued in the post partum period. The effect is beneficial for the
      neonate and helps women stop smoking during subsequent pregnancies. To date, no
      study has been conducted during the intrapartum period useful for adapting our
      clinical practice in patients who smoke during pregnancy. Prospective studies,
      specifically designed to measure the impact of smoking on maternal and fetal
      complications during labor are essential.

PMID- 15980797
TI  - [What diagnostic tools can be used to assess antenatal exposure to smoking?
      Pediatric experience].
AB  - In France, one out of four infants is born to a smoking mother. The short-, mid-,
      and long-term effects of antenatal exposure to smoking are only partially known.
      En Europe, it is generally accepted that most smoking mothers are aware of their
      smoking habit. Nevertheless, certain mothers deny their smoking or minimize the
      number of cigarettes smoked. The impact of anti-smoking campaigns on the
      frequency of maternal smoking and its recognition are unknown. The question is
      determine whether an objective marker of smoking in the neonatal period would be
      useful for individual care or epidemiological research. Cotinine and CO are the
      most widely used neonatalagy.

PMID- 15980798
TI  - [What diagnostic tools can be used to assess antenatal exposure to smoking?
      Toxicologist experience].
AB  - Based on a review of the literature and our toxicological experience, we present
      the diagnostic tools available for the clinician to explore and quantify the
      degree of ante-natal exposure to active and passive maternal smoking. Two types
      of tools are used to evaluate this fetal exposure:--Repeated measurement of bio
      markers of tobacco smoking enable and evaluation of the specific degree of
      nicotinic exposure for the pregnant women, the fetus (cord blood), the placenta
      and the newborn. The total fetal exposure during pregnancy can be extrapolated by
      combining these data. --Markers of toxicity related to active and passive
      maternal smoking (cadmium, cytochrome P450 CYP 1A1 activity). In the newborn, two
      biological tissues, meconium and hair, can be used to obtain an objective
      measurement of fetal exposure. Meconium concentrations of cotinine and trans-3'
      hydroxycotinine correctly reflect the nicotinic practices of the mother and
      neonatal hair concentrations of nicotine and cotinine confirm the systemic degree
      of long-term exposure.

PMID- 15980800
TI  - [The image of smoking women in France].
AB  - OBJECTIVES: The purpose of this work was to try to understand why the social
      image of the smoking woman remains positive and cannot be assimilated to that of
      the smoking man. We wanted to describe the typical status and function of smoking
      women in today's social imaginary in France. MATERIALS AND METHODS: We identified
      and interpreted selected images in which female smoking is presented as an
      ideological corpus. RESULTS: The cultural meaning of female and male smoking, as
      well as their pathological effects, are different and should not be apprehended
      symmetrically. The leading feministic culture deeply resists alarming discourses
      about the dangers of tobacco, considering them to have little importance. Female
      smoking is still encouraged and exalted for its emancipating power: tobacco
      liberates woman from an impracticable womanhood. CONCLUSION: There is a need for
      a political approach to female smoking, viewing it as a modern form of mutilation
      meant to compensate for the extension of women's rights. In order to fight
      against this imagery efficiently, it must be put into a critical perspective,
      eliminating taboos about certain feministic misunderstandings and dead-ends. A
      woman must be offered something more than smoking cessation: an improvement in
      her own being, a way to reappropriate her gendered identity.

PMID- 15980801
TI  - [What public health measures could reduce antenatal exposure to tobacco and
      improve the quality of perinatal care: the gynecologist-obstetrician's point of
      view].
AB  - The progression of addiction to smoking among young women is particularly
      alarming. The fatal effects of the nicotine-poisoning on the pregnancy and on the
      child constitute a serious public health issue. For young women, the period of
      maternity plays an essential educational role. Contact with medical care during
      pregnancy offers a special opportunity to establish a sound basis for health.
      Clinicians must strive to help women become fully aware of the fatal effects of
      smoking, providing methods and support for abstinence through a global,
      structured strategy of health care. The "Maternity without tobacco" network was
      developed to achieve these objectives. Expired CO analysis can be an interesting
      tool to search for active or passive addiction to smoking, and more generally
      carbon monoxide poisoning.

PMID- 15980799
TI  - [Neonatal management of a child exposed to tobacco smoke in utero].
AB  - The gravidic toxicity of the nicotinism on the fetus is now established. Certain
      long-term effects related to some substances, including certain unquestionable
      carcinogens, still remain to be evaluated. The risk of preterm birth is increased
      and the incidence of the intra-uterine growth retardation is high. Behavioral and
      physiological disorders, in particular metabolic, cardiac and respiratory
      disorders are observed from the first day of life. The risk of oro-facial
      malformations is not excluded. At mid-term the number of ORL and respiratory
      complications is higher and the risk of sudden infant death is almost doubled.
      The neonatale period should be used to assess the state of the newborn and to
      renew recommendations and advice for prevention. Breast feeding should and
      encouraged. This assessment also gives the mother an additional opportunity to
      reduce, to even cease smoking. A specialized consultation can be proposed if
      needed.

PMID- 15980802
TI  - [Smoking-related biological alterations in women: a way to start talking about
      smoking. The internist's point a view: the clinical biologist's point of view].
AB  - Besides biological markers such as cotinine, CO, and thiocyanate, other
      biological parameters are altered during pregnancy in women who smoke. Smoking
      women generally have a high white cell count which is related in part to
      pregnancy and in part to smoking but independently of other conditions. The mean
      corpuscular volume is increased, even in the absence of folate deficiency
      frequent in smoking pregnant women. The platelet count is higher than in the non
      smoking mothers and the physiological pregnancy-related hyperaggregability is
      increased. The hypercoagulability status during pregnancy does not appear to be
      worsened by smoking but is insufficiently counterbalanced by fibrolysis which is
      less active in the smoking pregnant woman. These factors increase the risk of
      venous thrombosis which remains one of the main factors of pregnancy-related
      mortality. There are also smoking-related lipid metabolism disorders which appear
      independently of the pregnancy-related variations: increased total cholesterol,
      LDL cholesterol, and triglycerides and decreased HDL cholesterol. Combined, these
      factors can have an effect on the arterial walls. Vitamin levels are also lower
      in smoking mothers compared with their non-smoking counterparts. Levels of
      vitamins C, A, B12 and folates are decreased. Finding these anomalies during
      pregnancy in smoking mothers can be a useful mean of inciting them to stop
      smoking.

PMID- 15980803
TI  - [Pregnancy and smoking: the occupational physician's point of view].
AB  - It has become urgent to initiate preventive measures to avoid occupation exposure
      of pregnant women to smoking. Tobacco smoke is a recognized cause of respiratory
      cancer and a large number of workers are exposed to substances classified as
      cancerogenic agents. The occupational physician can provide information on risks,
      measure biological markers (CO in ambient air, serum markers such as CO in
      expired air, carboxyhemoglobin or cotinine), counsel the employer concerning
      elimination of the secondary smoke current or the management of toxic materials,
      and propose modifications of the ventilation system. The current legislation
      (Evin law) should be included in the house rules. In the event a non-smoking
      pregnant woman is exposed to passive smoking, the work post should be adapted or
      changed. Smoking women should be encouraged to stop smoking and provided with the
      necessary support to achieve cessation. The woman's individual maternity book let
      should include information on the risk of smoking and encourage contact with the
      primary care physician, the gynecologist, or the anti-smoking care center. The
      occupational physician should search for addictive or occupational co-exposures.

PMID- 15980804
TI  - [What public health measures could reduce antenatal exposure to smoking and
      improve the quality of perinatal care? The point of view of a public health
      physician].
AB  - From the population standpoint of public health, two domains of intervention,
      healthcare programs and good clinical practices, are concerned by the question of
      smoking cessation. These two domains imply different targets and methodology to
      achieve a common objective. To achieve improvement starting from an analysis of
      the existing situation, it is necessary to elaborate guidelines for good clinical
      practice and also carefully monitor their application in terms of training,
      evaluation and certification. Health promotion programs designed to help young
      women stop or not start smoking necessarily imply the use of recognized criteria
      of efficacy and predictability.

PMID- 15980805
TI  - [What measures can be taken to reduce the number of smoking adolescents and young
      women?].
AB  - A proper understanding of the factors exposing adolescents and young women to the
      risk of smoking dependence is necessary to develop effective preventive measures.
      These measures will be different depending on whether they are designed for
      adolescents and young women in general or for the context of pregnancy. For
      adolescents, efforts should be continued to provide information about smoking and
      the dangers of tobacco as well as about the social manipulation involved. The
      image of a natural, active woman, free of tobacco and capable of making her own
      decisions should be promoted. Health education and communication professionals
      should make use of different media with an audience among the young. Messages
      should be validated with a target population before diffusion. A better coherence
      between the adult and young populations concerning legal obligations and mutual
      respect is significantly useful. Educational structures (schools and
      universities) should participate in long-term community projects implicating peer
      groups and trained professionals. Values which should be reinforced include self
      esteem, affirmation of personal competence and difference, self-respect and
      respect of others. Early identification of factors favoring psychosocial
      vulnerability at this age is indispensable to facilitate referral to professional
      support and care centers, the number of which remains insufficient to date.
      Support when ceasing smoking, based on individual and group assistance, should
      take into account the individual's phase of maturation, and must be proposed and
      operated by trained professionals working in a network. During pregnancy, it is
      crucial to recognize that the woman's specific physical and psychological
      situation is a unique opportunity to propose a new approach to smoking, taking
      into consideration the fragile context during this period of maturation and its
      impact on the woman's general life. Beyond sociopolitical measures and a
      philosophical debate on the position of women, men, and the family in the 21st
      century, propositions can be put forward for actions before, during and after the
      maternity period. It is important to continue the educational aspect without
      creating a guilt feeling. Messages should be elaborated with women. Healthcare
      professionals should be trained about smoking and smoking dependence. They should
      repeat minimal advice and continuously propose stopping smoking, taking into
      consideration the woman's stage of maturation and her motivation. Carbon monoxide
      monitoring should become a routine practice. Prognostic factors and possible
      difficulties should be identified early, if possible before pregnancy or at least
      during pregnancy, in order to propose adapted multidisciplinary support. The
      health booklet for the mother and the infant should be improved. Midwives should
      play an important role in prevention. A multidisciplinary effort will have the
      greatest impact: smoke-free environment in maternities, professional clinics, and
      the real-life territory of the pregnant woman. Individual care and support are
      more appropriate than group support. The partner should be implicated. For very
      dependent women, basically psychological support of smoking cessation should be
      completed with nicotine substitution therapy using protocols which should be
      redefined with more extensive studies. All these measures should be continued for
      six months after birth whether the woman has stopped smoking during pregnancy or
      not.

PMID- 15980806
TI  - [Smoking and pregnancy: the role of the gynecologist-obstetrician and the
      obstetrical team].
AB  - Pregnancy is a particular period of life which changes the woman's smoking
      behavior. One-third of smoking women stop smoking spontaneously during this
      period and a large proportion request help with smoking cessation. Gynecologist
      obstetricians who are concerned by the technical aspects of the pregnancy and
      other classical risk factors (gestational diabetes, hypertension) play an
      indispensable role, but together with the entire obstetrical team they must
      become more involved to fully take into account this toxic disease in their
      everyday practice. We report the experience of a level 1 maternity supported by
      the Lorrain Perinatal Network, the Association for Perinatal Prevention, Research
      and Information, and the work of our midwife anti-smoking team. The first step
      was better awareness. We shared our knowledge about the profile of the smoking
      mother and her expectations and about the usefulness of CO monitoring (prenatal
      consultations, hospital stay, delivery room). We then established a strategy for
      our entire healthcare facility involving minimal training for all categories of
      personnel, definition of screening and prevention modalities, and obstetrical
      care for smoking mothers. We also organized a smoking cessation supportive care
      program. Applied during outpatient consultations and hospital stays and in the
      delivery room, the program also included a smoking-cessation consultation with
      two midwives in the unit in cooperation with a physician and a dietitian working
      with smoking patients. A survey conducted in 24 maternity wards participating in
      the Lorrain Perinatal Network and five Perinatal Care Centers enabled an
      assessment of their participation in the smoking-cessation program and to
      evaluate their needs. Perinatal indicators are not satisfactory in France and it
      will be interesting to observe what changes can be achieved in each maternity
      ward after application of the smoking cessation care and support program.

PMID- 15980807
TI  - [Health Professionals' Interventions for promoting smoking cessation during
      pregnancy: a review of the evidence].
AB  - Active and passive exposure to tobacco smoke during pregnancy is the most serious
      and preventable cause of adverse maternal, fetal, and infant outcomes in France.
      The clinical and economic benefits of cessation have been documented. The
      objective of this article is to review the evidence base addressing smoking
      cessation in pregnant women. The article describes how best to assist the
      pregnant smoker in clinical practice or hospital to quit during pregnancy. The
      following low intensity interventions designed to be integrated into routine
      prenatal care are detailed: expired air CO measures, practice of the evidence
      based 5 A's smoking cessation intervention for pregnant women, use of pregnant
      woman's self-help guide to quit smoking, relapse prevention, health
      professionals' training, participation to community program.

PMID- 15980808
TI  - [The role of the community pharmacist in preventing smoking during pregnancy].
AB  - Being the most accessible health professionals, community pharmacists have a very
      important role in public information and health education. In the field of
      tobacco cessation, pharmacists are in the front line of contact with smokers and
      can propose the measure of expired carbon monoxide in order to help them in their
      decision to quit smoking. The pharmacists' involvement in smoking cessation is of
      particular importance for pregnant women because of the adverse maternal, fetal
      and infant outcomes of cigarette smoking during pregnancy.

PMID- 15980809
TI  - [Should the cost of smoking cessation aids with recognized efficacy be
      reimbursed?].
AB  - Smoking endangers the health of the mother and in the shorter term that of her
      child. As in many countries, smoking is insufficiently taken into account during
      pregnancy in France. However, some methods to quit smoking are proven to be
      effective (cognitive and behavioral techniques, nicotine replacement therapy).
      Financial support would increase the use of these methods. Many international
      recommendations are going in this direction. If there is a time to quit smoking,
      it is during a pregnancy. If there is a time to subsidize the cost of effective
      supports to quit smoking, it is during a pregnancy.

PMID- 15980810
TI  - [What are the epidemiological data on maternal and paternal smoking?].
AB  - A review of the literature published over the last fifteen years shows that
      active smoking (1.54 [95% CI 1.19-2.01]) and passive smoking (1.17 [95% CI1.02
      1.37]) are the cause of a decline in female fertility in the general population.
      This lower fertility is particularly evident for in vitro fecundation where the
      relative risk of infertility measured in one study was 2.41 (95% CI 1.07-5.45)
      and even 4.27 (95% CI 1.53-11.97) if the couple has smoked for five years.
      Paternal smoking at the time of IVF decreases the number of ovocytes by 46% due
      to maternal passive smoking. The risk of not having a live infant is high: 3.76
      (95% CI 1.40-10.03, p < 0.01). In the general population, active smoking
      increases the risk of spontaneous abortion by 60-100%, depending on the intensity
      of smoking. The latest report published in France shows that 37% of women declare
      they smoked before pregnancy. This rate decreased to 17% during the first
      trimester, 15% during the second and 14% during the third then rose again to
      20.5% two years after delivery. About half of the women who stopped smoking
      during pregnancy start again after delivery. The desire to breastfeed is lower
      among smokers, and fewer start breastfeeding which is continued for a shorter
      time. The effect of paternal smoking has not been described for this factor in
      France.

PMID- 15980811
TI  - [What are the consequences of smoking on pregnancy and delivery].
AB  - According to a WHO report of 1997, more than one-third of the world population of
      more than 15 years old smokes. Since the 90s, smoking progressed amongst women
      and teenagers. The noxious roles of smoking addiction to smoking on male and
      female fertility, pregnancy and delivery are often little known or underestimated
      by the public and most healthcare professionals. In France, smoking addiction
      provokes 60,000 deaths every year and is one of the first avoidable perinatal
      causes of mortality and morbidity. The alarming extension of the epidemic of the
      feminine addiction to smoking has increased the number of complications
      (infertilities, ectopic pregnancy, premature abortions, premature delivery, intra
      uterine growth retardation).

PMID- 15980812
TI  - [What is appropriate care for women who smoke during pregnancy?].
AB  - There are few publications on smoking biomarkers in pregnant woman, but nothing
      suggests that their contribution differs during pregnancy. Many publications have
      examined the predictive value of the biomarkers of smoking, but the comparative
      value is not clear. To our knowledge no study has used biomarkers of the smoking
      to monitor smoking cessation during pregnancy. Blood nicotine is not retained as
      a useful biomarker. Most authors retain urinary cotinine as the gold standard.
      There is no consensus on measurement techniques. Cotinine can be measured in
      blood, saliva and in cord blood. Active and passive smoking can be monitored with
      urinary cotinine. Rapid strip tests provide useful results to differentiate
      smokers from non-smokers, but not to quantify nicotinic intoxication. All
      published papers have been supported by the firm marketing the strip. There have
      been few studies in pregnant woman on expired CO rate, but the method is
      validated. Measurement of thiocyanates and other biomarkers does not currently
      provide useful information for routine surveillance of pregnant smoking women.

PMID- 15980813
TI  - [What are the short, mid, and long term consequences of smoking during
      pregnancy?].
AB  - A review of the literature shows that maternal or paternal smoking during
      pregnancy has many effects on the newborn, the infant, and even the adult exposed
      during intrauterine life. In the newborn, measurements at birth are lower than
      those observed in non-exposed newborns and the risk of preterm birth is
      increased. There is also a slightly increased risk of cleft lip or palate.
      Newborns exposed to smoking also suffer from altered vascular and pulmonary
      function and have a different neurological behavior. They react less well to
      stress. The risk of sudden infant death is significantly increased among exposed
      infants, especially if they sleep with their parents. The overall mortality of
      exposed infants is higher. Mid- and long-term consequences are more difficult to
      evaluate due to the very large number of confounding factors. There is however an
      association between maternal smoking during pregnancy and a slightly decreased
      cognitive level in childhood and adulthood. The risks of hyperactivity disorder
      with attentional deficit, behavioral disorders, delinquency, and childhood and
      adolescence smoking are increased as are the risks of obesity, respiratory
      disorders and infection. Conversely, there is no demonstrated link with childhood
      cancer.

PMID- 15980814
TI  - [Obstetrical and anesthetic management of pregnant women who smoke].
AB  - Is the obstetrical and anesthetic management of pregnant women who smoke
      different from that for a pregnant women who does not smoke? This was the
      question the experts were asked during the first "Tobacco and pregnancy"
      Consensus Conference. To address these two questions a Medline and Embase search
      was carried out. The review of the literature confirmed the limited number of
      reported studies directly concerned, from the obstetrical or anesthesia point of
      view, with the problems of the management of women who smoke. Consequently, we
      are not able to suggest detailed recommendations. However, during the perinatal
      period, the correlation between tobacco and some obstetrical or surgical
      complications have been established. On this basis, studies must be undertaken in
      order to propose an optimal attitude for pregnant smokers.

PMID- 15980815
TI  - [Neonatal management of a child exposed to tobacco in utero and postnatal
      biomarkers].
AB  - Does neonatal and postnatal management of a new-born exposed in utero to tobacco
      smoking differ from a non-exposed neonate? Which are the biomarkers for perinatal
      exposition? In order to address these two questions a Medline and Embase search
      was carried out. For the first question, the review of the literature suggests
      that tobacco is one of main factors increasing the rates of preterm birth to a
      significant degree and primarily early prematurity, and intrauterine growth
      restriction. Moreover, maternal smoking during pregnancy increases perinatal
      mortality. Management tends to reduce perinatal morbidity and mortality of these
      new-born, but there is in fact no published research which proposes precise
      recommendations for an accurate management distinct from the non-exposed child.
      Among the biomarkers used for the routine diagnosis of in utero tobacco smoke
      exposure, the umbilical cord cotinine level is probably the most reliable and
      noninvasive for the new-born. However, the maternal curve can be studied and
      measurement of the exhaled carbon monoxide in late pregnancy is a valid
      reflection of neonatal impregnation.

PMID- 15980816
TI  - [Public health measures studied in order to reduce antenatal exposure to tobacco:
      review of literature].
AB  - INTRODUCTION: One of the questions raised by the Consensus conference "Pregnancy
      and Tobacco" conducted in October 2004 in France concerned the public health
      measures which should be studied to reduce antenatal exposure to tobacco.
      METHODS: We conducted a review of the literature on the following topics: smoking
      cessation interventions, smoking cessation biochemical validation, role of health
      professionals in smoking cessation and financial coverage of smoking cessation
      programs for pregnant women. RESULTS: Smoking cessation interventions during
      pregnancy lead to a lower rate of low birth weight, a reduction of preterm births
      and an increase in average birth weight. Biochemical validation of smoking
      cessation is necessary for both scientific and educational purposes. The role of
      health professionals in smoking cessation has been proved to be effective.
      CONCLUSION: Implementation of smoking cessation programs tailored for pregnant
      women is necessary in France, after appropriate training of health professionals.
      A study should be set up to test the efficacy of Nicotine Replacement Therapy
      (NRT) on smoking cessation during pregnancy.

PMID- 15980819
TI  - A win win scenario.

PMID- 15980820
TI  - Missed diagnosis.

PMID- 15980821
TI  - Overseas dentists.

PMID- 15980831
TI  - Anterior dental aesthetics: historical perspective.
AB  - The purpose of this series is to convey the principles governing our aesthetic
      senses. Usually meaning visual perception, aesthetics is not merely limited to
      the ocular apparatus. The concept of aesthetics encompasses both the time - arts
      such as music, theatre, literature and film, as well as space - arts such as
      paintings, sculpture and architecture.

PMID- 15980832
TI  - Paraesthesia of the lip and chin area resolved by endodontic treatment: A case
      report and review of literature.
AB  - Lower lip numbness is a symptom that may be due to entirely benign causes, or it
      may be the first sign of a more sinister problem. It has been reported as being
      the sole symptom of pathological lesions and metastatic tumours in the mandible.

PMID- 15980833
TI  - Unicystic ameloblastoma presenting in Gardner's syndrome: a case report.
AB  - An unusual case of a unicystic Ameloblastoma mimicking a dentigerous cyst in a 14
      year-old patient with Gardner's Syndrome is described. Gardner's Syndrome is
      associated with multiple tumours and dental anomalies.

PMID- 15980834
TI  - Severe tissue damage and neurological deficit following extravasation of sodium
      hypochlorite solution during routine endodontic treatment.
AB  - Endodontic therapy is a routinely practised clinical procedure with few reported
      complications. Sodium hypochlorite is often used as an irrigant during this
      procedure, but severe complications may occur if this solution extravasates
      beyond the root apex. We present a case demonstrating some of the severe sequelae
      that can occur following the misuse of sodium hypochlorite during endodontic
      treatment of an upper lateral incisor, which also resulted in the previously
      unreported complication of isolated facial nerve weakness.

PMID- 15980841
TI  - Dental irrigators.

PMID- 15980842
TI  - Periodontology in the UK.

PMID- 15980843
TI  - Oral & maxillofacial services.

PMID- 15980844
TI  - Endodontics series.

PMID- 15980845
TI  - An outcome audit of the treatment of acute dentoalveolar infection: impact of
      penicillin resistance.
AB  - OBJECTIVES: The aim of this audit was to measure the outcome of treatment of
      acute dentoalveolar infection and to determine if this was influenced by choice
      of antibiotic therapy or the presence of penicillin-resistance. SUBJECTS AND
      METHODS: A total of 112 patients with dentoalveolar infection were included in
      the audit. All patients underwent drainage, either incisional (n=105) or opening
      of the pulp chamber (n=7) supplemented with antibiotic therapy. A pus specimen
      was obtained from each patient for culture and susceptibility. Clinical signs and
      symptoms were recorded at the time of first presentation and re-evaluated after
      48 or 72 h. RESULTS: A total of 104 (99%) of the patients who underwent
      incisional drainage exhibited improvement after 72 h. Signs and symptoms also
      improved in five of the seven patients who underwent drainage by opening of the
      root canal although the degree of improvement was less than that achieved by
      incisional drainage. Penicillin-resistant bacteria were found in 42 (38%) of the
      112 patients in this study. Of the 65 patients who were given penicillin, 28 had
      penicillin-resistant bacteria. There was no statistical difference in the
      clinical outcome with regard to the antibiotic prescribed and the presence of
      penicillin-resistant bacteria. Strains of penicillin-resistant bacteria were
      isolated more frequently in patients who had previously received penicillin
      (p<0.05). CONCLUSION: Incisional drainage appeared to produce a more rapid
      improvement compared to drainage by opening of the root canal. The presence of
      penicillin-resistant bacteria did not adversely affect the outcome of treatment.
      The observations made support surgical drainage as the first principle of
      management and question the value of prescribing penicillin as part of treatment.

PMID- 15980846
TI  - The influence of self-deception and impression management upon self-assessment in
      oral surgery.
AB  - OBJECTIVE: To see if poor self-assessment of surgical performance during removal
      of mandibular third molars is influenced by self-deception (lack of insight) and
      impression management (trying to convey a favourable impression). DESIGN: A
      prospective study of 50 surgeons, surgically removing a lower third molar tooth.
      SETTING: One UK dental school over a two year period. METHODS: The surgeons'
      surgical skills were assessed (by two assessors) and self-assessed using check
      list and global rating scales. Post-operatively, surgeons completed validated
      deception questionnaires which measured both self-deception enhancement (lack of
      insight), and impression management (the tendency to deliberately convey a
      favourable impression). MAIN OUTCOME MEASURES: Reliability between assessors, and
      between assessors' and surgeons' self-assessments were calculated. Discrepancies
      between assessors' and surgeons' scores were correlated with surgeons' deception
      scores. RESULTS: Reliability between assessors was excellent for checklist (0.96)
      and global rating scales (0.89) and better than the reliability between assessors
      and surgeons (0.51 and 0.49). There was a statistically significant correlation
      (r=0.45 p=0.001 checklist, r= 0.48 p<0.001 global) between over/ under-rating of
      their surgical performance by surgeons and their impression management scores. No
      statistically significant correlation was found between this inaccuracy in self
      assessment and surgeons' individual self-deception scores. CONCLUSION: The
      majority of surgeons scored themselves higher than their assessors did for
      surgical skill in removing a single mandibular third molar tooth. Impression
      management (the tendency to deliberately convey a favourable impression) may
      contribute to a surgeon's inaccurate self-reporting of performance. Lack of
      insight appears to be much less important as a contributing factor. The authors
      speculate that pressure to provide evidence of good performance may be
      encouraging surgeons to manage their image and over-score themselves.

PMID- 15980847
TI  - An investigation of the acceptability of undergraduate supervision by Senior
      House Officers and General Professional Trainees.
AB  - AIM: This study assessed whether Senior House Officers (SHO)/General Professional
      Trainees (GPT) are, or would be, comfortable supervising clinical undergraduates,
      whether they find this to be a valuable experience within their training
      programme, and whether undergraduates are or would be comfortable with SHO/GPTs
      supervising them. METHOD: Questionnaires were distributed to fourth and final
      year students at Glasgow and Dundee Dental Schools and fourth year students at
      Newcastle Dental School. Questionnaires were also distributed to SHO/GPTs at
      Glasgow Dental Hospital and School and Edinburgh Dental Institute. RESULTS:
      Seventy-nine per cent of respondent SHO/GPTs were currently not involved in the
      supervision of undergraduates within their present rotation, 65% of whom stated
      that they would value the experience of this within their training. Of those
      involved in supervision, 83% found the experience valuable. Forty-four per cent
      of students were unsure or not comfortable with SHO/GPTs supervising within an
      oral surgery department and approximately the same in other departments. Twenty
      eight per cent of respondents felt that university lecturers should be the main
      trainer. CONCLUSION: SHO/GPTs value supervising undergraduates as part of their
      training experience. More than half of students are comfortable with SHO/GPTs
      supervising them. Both groups suggest that SHO/GPTs should receive some form of
      training in teaching prior to supervising undergraduates.

PMID- 15980860
TI  - A new family of RhoGEFs activates the Rop molecular switch in plants.
AB  - In plants, the small GTP-binding proteins called Rops work as signalling switches
      that control growth, development and plant responses to various environmental
      stimuli. Rop proteins (Rho of plants, Rac-like and AtRac in Arabidopsis thaliana)
      belong to the Rho family of Ras-related GTP-binding proteins that turn on
      signalling pathways by switching from a GDP-bound inactive to a GTP-bound active
      conformation. Activation depends on guanine nucleotide exchange factors (GEFs)
      that catalyse the otherwise slow GDP dissociation for subsequent GTP binding.
      Although numerous RhoGEFs exist in animals and yeasts, no Rop-specific GEFs have
      yet been identified in plants and so Rop activation has remained elusive. Here we
      describe a new family of RhoGEF proteins that are exclusive to plants. We define
      a unique domain within these RopGEFs, termed PRONE (plant-specific Rop nucleotide
      exchanger), which is exclusively active towards members of the Rop subfamily. It
      increases nucleotide dissociation from Rop more than a thousand-fold and forms a
      tight complex with nucleotide-free Rop. RopGEFs may represent the missing link in
      signal transduction from receptor kinases to Rops and their identification has
      implications for the evolution of the Rho molecular switch.

PMID- 15980861
TI  - Complete genome sequence of the plant commensal Pseudomonas fluorescens Pf-5.
AB  - Pseudomonas fluorescens Pf-5 is a plant commensal bacterium that inhabits the
      rhizosphere and produces secondary metabolites that suppress soilborne plant
      pathogens. The complete sequence of the 7.1-Mb Pf-5 genome was determined. We
      analyzed repeat sequences to identify genomic islands that, together with other
      approaches, suggested P. fluorescens Pf-5's recent lateral acquisitions include
      six secondary metabolite gene clusters, seven phage regions and a mobile genomic
      island. We identified various features that contribute to its commensal lifestyle
      on plants, including broad catabolic and transport capabilities for utilizing
      plant-derived compounds, the apparent ability to use a diversity of iron
      siderophores, detoxification systems to protect from oxidative stress, and the
      lack of a type III secretion system and toxins found in related pathogens. In
      addition to six known secondary metabolites produced by P. fluorescens Pf-5,
      three novel secondary metabolite biosynthesis gene clusters were also identified
      that may contribute to the biocontrol properties of P. fluorescens Pf-5.

PMID- 15980862
TI  - Dynein mutations impair autophagic clearance of aggregate-prone proteins.
AB  - Mutations that affect the dynein motor machinery are sufficient to cause motor
      neuron disease. It is not known why there are aggregates or inclusions in
      affected tissues in mice with such mutations and in most forms of human motor
      neuron disease. Here we identify a new mechanism of inclusion formation by
      showing that decreased dynein function impairs autophagic clearance of aggregate
      prone proteins. We show that mutations of the dynein machinery enhanced the
      toxicity of the mutation that causes Huntington disease in fly and mouse models.
      Furthermore, loss of dynein function resulted in premature aggregate formation by
      mutant huntingtin and increased levels of the autophagosome marker LC3-II in both
      cell culture and mouse models, compatible with impaired autophagosome-lysosome
      fusion.

PMID- 15980863
TI  - Nonstimulatory peptides contribute to antigen-induced CD8-T cell receptor
      interaction at the immunological synapse.
AB  - It is unclear if the interaction between CD8 and the T cell receptor (TCR)-CD3
      complex is constitutive or antigen induced. Here, fluorescence resonance energy
      transfer microscopy between fluorescent chimeras of CD3zeta and CD8beta showed
      that this interaction was induced by antigen recognition in the immunological
      synapse. Nonstimulatory endogenous or exogenous peptides presented simultaneously
      with antigenic peptides increased the CD8-TCR interaction. This finding indicates
      that the interaction between the intracellular regions of a TCR-CD3 complex
      recognizing its cognate peptide-major histocompatibility complex (MHC) antigen,
      and CD8 (plus the kinase Lck), is enhanced by a noncognate CD8-MHC interaction.
      Thus, the interaction of CD8 with a nonstimulatory peptide-MHC complex helps
      mediate T cell recognition of antigen, improving the coreceptor function of CD8.

PMID- 15980864
TI  - Genomic instability in laminopathy-based premature aging.
AB  - Premature aging syndromes often result from mutations in nuclear proteins
      involved in the maintenance of genomic integrity. Lamin A is a major component of
      the nuclear lamina and nuclear skeleton. Truncation in lamin A causes Hutchinson
      Gilford progerial syndrome (HGPS), a severe form of early-onset premature aging.
      Lack of functional Zmpste24, a metalloproteinase responsible for the maturation
      of prelamin A, also results in progeroid phenotypes in mice and humans. We found
      that Zmpste24-deficient mouse embryonic fibroblasts (MEFs) show increased DNA
      damage and chromosome aberrations and are more sensitive to DNA-damaging agents.
      Bone marrow cells isolated from Zmpste24-/- mice show increased aneuploidy and
      the mice are more sensitive to DNA-damaging agents. Recruitment of p53 binding
      protein 1 (53BP1) and Rad51 to sites of DNA lesion is impaired in Zmpste24-/-
      MEFs and in HGPS fibroblasts, resulting in delayed checkpoint response and
      defective DNA repair. Wild-type MEFs ectopically expressing unprocessible
      prelamin A show similar defects in checkpoint response and DNA repair. Our
      results indicate that unprocessed prelamin A and truncated lamin A act dominant
      negatively to perturb DNA damage response and repair, resulting in genomic
      instability which might contribute to laminopathy-based premature aging.

PMID- 15980866
TI  - Control of mRNA translation preserves endoplasmic reticulum function in beta
      cells and maintains glucose homeostasis.
AB  - Type 2 diabetes is a disorder of hyperglycemia resulting from failure of beta
      cells to produce adequate insulin to accommodate an increased metabolic demand.
      Here we show that regulation of mRNA translation through phosphorylation of
      eukaryotic initiation factor 2 (eIF2alpha) is essential to preserve the integrity
      of the endoplasmic reticulum (ER) and to increase insulin production to meet the
      demand imposed by a high-fat diet. Accumulation of unfolded proteins in the ER
      activates phosphorylation of eIF2alpha at Ser51 and inhibits translation. To
      elucidate the role of this pathway in beta-cell function we studied glucose
      homeostasis in Eif2s1(tm1Rjk) mutant mice, which have an alanine substitution at
      Ser51. Heterozygous (Eif2s1(+/tm1Rjk)) mice became obese and diabetic on a high
      fat diet. Profound glucose intolerance resulted from reduced insulin secretion
      accompanied by abnormal distension of the ER lumen, defective trafficking of
      proinsulin, and a reduced number of insulin granules in beta cells. We propose
      that translational control couples insulin synthesis with folding capacity to
      maintain ER integrity and that this signal is essential to prevent diet-induced
      type 2 diabetes.

PMID- 15980867
TI  - A single active-site region for a group II intron.
AB  - Despite the biological importance of self-splicing group II introns, little is
      known about their structural organization. Synthetic incorporation of site
      specific photo-cross-linkers within catalytic domains resulted in functional
      distance constraints that, when combined with known tertiary interactions,
      provide a three-dimensional view of the active intron architecture. All
      functionalities important for both steps of splicing are proximal before the
      first step, suggestive of a single active-site region for group II intron
      catalysis.

PMID- 15980865
TI  - Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases.
AB  - The Poxviridae family members vaccinia and variola virus enter mammalian cells,
      replicate outside the nucleus and produce virions that travel to the cell surface
      along microtubules, fuse with the plasma membrane and egress from infected cells
      toward apposing cells on actin-filled membranous protrusions. We show that cell
      associated enveloped virions (CEV) use Abl- and Src-family tyrosine kinases for
      actin motility, and that these kinases act in a redundant fashion, perhaps
      permitting motility in a greater range of cell types. Additionally, release of
      CEV from the cell requires Abl- but not Src-family tyrosine kinases, and is
      blocked by STI-571 (Gleevec), an Abl-family kinase inhibitor used to treat
      chronic myelogenous leukemia in humans. Finally, we show that STI-571 reduces
      viral dissemination by five orders of magnitude and promotes survival in infected
      mice, suggesting possible use for this drug in treating smallpox or complications
      associated with vaccination. This therapeutic approach may prove generally
      efficacious in treating microbial infections that rely on host tyrosine kinases,
      and, because the drug targets host but not viral molecules, this strategy is much
      less likely to engender resistance compared to conventional antimicrobial
      therapies.

PMID- 15980868
TI  - Opioid tolerance in periaqueductal gray neurons isolated from mice chronically
      treated with morphine.
AB  - The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic
      action, and a significant site of cellular adaptations to chronic morphine
      treatment (CMT). We examined mu-opioid receptor (MOP) regulation of voltage-gated
      calcium channel currents (I(Ca)) and G-protein-activated K channel currents
      (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg(-1)
      of morphine base in a slow release emulsion three times over 5 days, or with
      emulsion alone (vehicles). This protocol produced significant tolerance to the
      antinociceptive effects of morphine in a test of thermal nociception. Voltage
      clamp recordings were made of I(Ca) in acutely isolated PAG neurons and GIRK in
      PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin)
      inhibited I(Ca) in neurons from CMT mice (230 nM) with a similar potency to
      vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in
      vehicle neurons, 27% in CMT neurons). Inhibition of I(Ca) by the GABA(B) agonist
      baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded
      in PAG slices were significantly smaller in neurons from CMT mice than vehicles,
      while GIRK currents activated by baclofen were unaltered. These data demonstrate
      that CMT-induced antinociceptive tolerance is accompanied by homologous reduction
      in the effectiveness of MOP agonists to inhibit I(Ca) and activate GIRK. Thus, a
      reduction in MOP number and/or functional coupling to G proteins accompanies the
      characteristic cellular adaptations to CMT previously described in PAG neurons.

PMID- 15980869
TI  - The hypoglycaemic activity of fenugreek seed extract is mediated through the
      stimulation of an insulin signalling pathway.
AB  - The in vivo hypoglycaemic activity of a dialysed fenugreek seed extract (FSE) was
      studied in alloxan (AXN)-induced diabetic mice and found to be comparable to that
      of insulin (1.5 U kg(-1)). FSE also improved intraperitoneal glucose tolerance in
      normal mice. The mechanism by which FSE attenuated hyperglycaemia was
      investigated in vitro. FSE stimulated glucose uptake in CHO-HIRc-mycGLUT4eGFP
      cells in a dose-dependent manner. This effect was shown to be mediated by the
      translocation of glucose transporter 4 (GLUT4) from the intracellular space to
      the plasma membrane. These effects of FSE on GLUT4 translocation and glucose
      uptake were inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI3-K)
      inhibitor, and bisindolylmaleimide 1, a protein kinase C (PKC)-specific
      inhibitor. In vitro phosphorylation analysis revealed that, like insulin, FSE
      also induces tyrosine phosphorylation of a number of proteins including the
      insulin receptor, insulin receptor substrate 1 and p85 subunit of PI3-K, in both
      3T3-L1 adipocytes and human hepatoma cells, HepG2. However, unlike insulin, FSE
      had no effect on protein kinase B (Akt) activation. These results suggest that in
      vivo the hypoglycaemic effect of FSE is mediated, at least in part, by the
      activation of an insulin signalling pathway in adipocytes and liver cells.

PMID- 15980870
TI  - Nonphotic entrainment of the circadian body temperature rhythm by the selective
      ORL1 receptor agonist W-212393 in rats.
AB  - We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2
      {3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo-benzimidazol-1-yl}
      N-methylacetamide (W-212393), and investigated its effect on the circadian body
      temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors in the
      rat cerebral cortex and human ORL1 receptors expressed in HEK293 cells with K(i)
      values of 0.76 and 0.50 nM, respectively. W-212393 concentration-dependently
      stimulated GTPgamma(35)S binding and its efficacy was similar to
      nociceptin/orphanin FQ (N/OFQ), suggesting that W-212393 is a full agonist at
      ORL1 receptors. W-212393 dose-dependently occupied ORL1 receptors following
      intraventricular or intraperitoneal administration, suggesting that W-212393 is a
      brain-penetrating compound. W-212393 (100 nM) and N/OFQ (100 nM) significantly
      suppressed the activity of spontaneously firing rat suprachiasmatic nucleus
      neurons. These suppressive effects were blocked by an ORL1 receptor antagonist, J
      113397 (1 microM). W-212393 (3 mg kg(-1), i.p.) induced a significant phase
      advance at circadian time 6 (CT6) and CT9, but not at other CTs. The magnitude of
      the W-212393 (0.3-3 mg kg(-1), i.p.)-induced phase advance was dose-dependent and
      greater than those produced by 8-hydroxy-2-(di-n-propylamino)tetralin (0.3-3 mg
      kg(-1), i.p.) or melatonin (0.3-3 mg kg(-1), i.p.). The W-212393 (3 mg kg(-1),
      i.p.)-induced phase advance was antagonized by J-113397 (10 mg kg(-1), i.p.).W
      212393 (3 mg kg(-1), i.p.) significantly accelerated the re-entrainment of the
      body temperature rhythm to a 6 h advanced light-dark cycle. These results
      indicate that activation of ORL1 receptors contributes to the circadian
      entrainment and W-212393 may represent an interesting agent for the study of
      circadian rhythms.

PMID- 15980871
TI  - Evaluation of benzyltetrahydroisoquinolines as ligands for neuronal nicotinic
      acetylcholine receptors.
AB  - Effects of derivatives of coclaurine (C), which mimic the 'eastern' or the
      nonquaternary halves of the alkaloids tetrandrine or d-tubocurarine,
      respectively, both of which are inhibitors of nicotinic acetylcholine receptors
      (nACh), were examined on recombinant, human alpha7, alpha4beta2 and alpha4beta4
      nACh receptors expressed in Xenopus oocytes and clonal cell lines using two
      electrode voltage clamping and radioligand binding techniques. In this limited
      series, Cs have higher affinity and are most potent at alpha4 subunit-containing
      nACh receptors and least potent at homomeric alpha7 receptors, and this trend is
      very marked for the N-unsubstituted C and its O,O'-bisbenzyl derivative. 7-O
      Benzyl-N-methylcoclaurine (BBCM) and its 12-O-methyl derivative showed the
      highest affinities and potencies at all three receptor subtypes, and this
      suggests that lipophilicity at C7 and/or C12 increases potency. Laudanosine and
      armepavine (A) were noncompetitive and voltage-dependent inhibitors of alpha7,
      alpha4beta2 or alpha4beta4 receptors, but the bulkier C7-benzylated 7BNMC (7-O
      benzyl-N-methylcoclaurine) and 7B12MNMC (7-O-benzyl-N,12-O-dimethyl coclaurine)
      were voltage-independent, noncompetitive inhibitors of nACh receptors. Voltage
      dependence was also lost on going from A to its N-ethyl analogue. These studies
      suggest that C derivatives may be useful tools for studies characterising the
      antagonist and ion channel sites on human alpha7, alpha4beta2 or alpha4beta4 nACh
      receptors and for revealing structure-function relationships for nACh receptor
      antagonists.

PMID- 15980872
TI  - Sildenafil citrate and sildenafil nitrate (NCX 911) are potent inhibitors of
      superoxide formation and gp91phox expression in porcine pulmonary artery
      endothelial cells.
AB  - Acute respiratory distress syndrome (ARDS) is associated with increased
      superoxide (O(2)(*-)) formation in the pulmonary vasculature and negation of the
      bioavailability of nitric oxide (NO). Since NO inhibits NADPH oxidase expression
      through a cyclic GMP-mediated mechanism, sildenafil, a type V phosphodiesterase
      inhibitor, may be therapeutically effective in ARDS through an augmentation of NO
      mediated inhibition of NADPH oxidase. Therefore, the effect of sildenafil citrate
      and NO-donating sildenafil (NCX 911) on O(2)(*-) formation and gp91(phox) (active
      catalytic subunit of NADPH oxidase) expression was investigated in cultured
      porcine pulmonary artery endothelial cells (PAECs). PAECs were incubated with 10
      nM TXA(2) analogue, 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prostaglandin
      F(2alpha) (U46619) (+/-sildenafil or NCX 911), for 16 h and O(2)(*-) formation
      measured spectrophometrically and gp91(phox) using Western blotting. The role of
      the NO-cGMP axis was studied using morpholinosydnonimine hydrochloride (SIN-1),
      the diethylamine/NO complex (DETA-NONOate), the guanylyl cyclase inhibitor, 1H
      {1,2,4}oxadiazolo{4,3-a}quinoxalin-1-one (ODQ), and the protein kinase G
      inhibitor, 8-bromoguanosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Br
      cGMPS). NO release was studied using a fluorescence assay and O(2)(*-)-NO
      interactions by measuring nitrites. After a 16-h incubation with 10 nM U46619,
      both NCX 911 and sildenafil elicited a concentration-dependent inhibition of
      O(2)(*-) formation and gp91(phox) expression, NCX 911 being more potent (IC(50);
      0.26 nM) than sildenafil citrate (IC(50); 1.85 nM). These inhibitory effects were
      reversed by 1 microM ODQ and 10 microM Rp-8-Br-cGMPS. NCX 911 stimulated the
      formation of cGMP in PAECs and generated NO in a cell-free system to a greater
      degree than sildenafil citrate. The inhibitory effect of sildenafil was augmented
      by 1 muM SIN-1 and blocked partially by the eNOS inhibitor 10 microM N(5)-(1
      iminoethyl)-ornithine (L-NIO). Acutely, sildenafil and NCX 911 also inhibited
      O(2)(*-) formation, again blocked by 1 microM ODQ. NCX 911 reacted with O(2)(*-)
      generated by xanthine oxidase, an effect that was inhibited by superoxide
      dismutase (500 U ml(-1)). Since O(2)(*-) formation plays contributory role in
      ARDS, both sildenafil citrate and NCX 911 may be indicated for treating ARDS
      through suppression of NADPH oxidase expression and therefore of O(2)(*-)
      formation and preservation of NO bioavailability.

PMID- 15980873
TI  - Electrophysiological and haemodynamic effects of endothelin ETA and ETB receptors
      in normal and ischaemic working rabbit hearts.
AB  - The aims of this study were to determine if endothelin-1 (ET-1) under normal and
      ischaemic conditions exhibits a direct arrhythmogenic effect that is independent
      of its ability to cause coronary vasoconstriction, and to determine the
      contribution of the ET(A) and ET(B) receptor subtype. ET(A/B) (with ET-1) and
      ET(A) (ET-1 in the presence of BQ-788) receptor activation resulted in a
      significant reduction in both epi- and endocardial monophasic action potential
      duration (MAPD(90)). ET(A) receptor activation reduced both epi- and endocardial
      effective refractory period (ERP). This MAPD(90) and ERP shortening were
      associated with a reduction in coronary flow, myocardial contractility and
      induction of ventricular fibrillation (VF) during ERP measurement. The ET(B)
      agonist sarafotoxin (S6c) had no marked, or concentration-dependent, effect on
      MAPD(90), ERP, myocardial contractility or induction of arrhythmias. Neither ET-1
      nor S6c, given prior to coronary artery occlusion, significantly changed the
      ischaemia-induced dispersion of MAPD(90), ERP or the % incidence of VF. In
      conclusion, neither ET(A) nor ET(B) receptor stimulation has a direct
      arrhythmogenic effect in isolated rabbit hearts under normal or ischaemic
      conditions. The ET-1-induced arrhythmogenic effect observed in nonischaemic
      hearts is likely to be the result of the associated coronary vasoconstriction
      caused by ET(A) receptor stimulation resulting in myocardial ischaemia.

PMID- 15980874
TI  - Spironolactone and its main metabolite canrenoic acid block hKv1.5, Kv4.3 and
      Kv7.1 + minK channels.
AB  - Both spironolactone (SP) and its main metabolite, canrenoic acid (CA), prolong
      cardiac action potential duration and decrease the Kv11.1 (HERG) current. We
      examined the effects of SP and CA on cardiac hKv1.5, Kv4.3 and Kv7.1+minK
      channels that generate the human I(Kur), I(to1) and I(Ks), which contribute to
      the control of human cardiac action potential duration.hKv1.5 currents were
      recorded in stably transfected mouse fibroblasts and Kv4.3 and Kv7.1 + minK in
      transiently transfected Chinese hamster ovary cells using the whole-cell patch
      clamp. SP (1 microM) and CA (1 nM) inhibited hKv1.5 currents by 23.2 +/- 3.2 and
      18.9 +/- 2.7%, respectively, shifted the midpoint of the activation curve to more
      negative potentials and delayed the time course of tail deactivation.SP (1
      microM) and CA (1 nM) inhibited the total charge crossing the membrane through
      Kv4.3 channels at +50 mV by 27.1 +/- 6.4 and 27.4 +/- 5.7%, respectively, and
      accelerated the time course of current decay. CA, but not SP, shifted the
      inactivation curve to more hyperpolarised potentials (V(h)-37.0 +/- 1.8 vs -40.8
      +/- 1.6 mV, n = 10, P < 0.05).SP (10 microM) and CA (1 nM) also inhibited Kv7.1 +
      minK currents by 38.6 +/- 2.3 and 22.1 +/- 1.4%, respectively, without modifying
      the voltage dependence of channel activation. SP, but not CA, slowed the time
      course of tail current decay.CA (1 nM) inhibited the I(Kur) (29.2 +/- 5.5%) and
      the I(to1) (16.1 +/- 3.9%) recorded in mouse ventricular myocytes and the I(K)
      (21.8 +/- 6.9%) recorded in guinea-pig ventricular myocytes.A mathematical model
      of human atrial action potentials demonstrated that K(+) blocking effects of CA
      resulted in a lengthening of action potential duration, both in normal and atrial
      fibrillation simulated conditions. The results demonstrated that both SP and CA
      directly block hKv1.5, Kv4.3 and Kv7.1 + minK channels, CA being more potent for
      these effects. Since peak free plasma concentrations of CA ranged between 3 and
      16 nM, these results indicated that blockade of these human cardiac K(+) channels
      can be observed after administration of therapeutic doses of SP. Blockade of
      these cardiac K(+) currents, together with the antagonism of the aldosterone
      proarrhythmic effects produced by SP, might be highly desirable for the treatment
      of supraventricular arrhythmias.

PMID- 15980875
TI  - Effects of (2R)-(3-amino-2-fluoropropyl)sulphinic acid (AFPSiA) on transient
      lower oesophageal sphincter relaxation in dogs and mechanism of hypothermic
      effects in mice.
AB  - The effects of the novel GABA analogue (2R)-(3-amino-2-fluoropropyl)sulphinic
      acid (AFPSiA) on transient lower oesophageal sphincter relaxations (TLOSRs) were
      studied in the dog. In addition, the GABA(A)/GABA(B) selectivity was determined
      in vitro and in vivo, and the pharmacokinetics and the metabolism of the compound
      were studied in the dog and rat. TLOSRs were reduced by 55 +/- 8% after
      intragastric administration of AFPSiA at 14 mumol kg(-1) and did not decrease
      further at higher doses. When evaluated 2 and 4 h after administration, the
      effect declined to 37 +/- 6 and 16 +/- 9%, respectively. Spontaneous swallowing
      was only significantly inhibited at 100 micromol kg(-1). The oral availability of
      AFPSiA was 52 +/- 17 and 71 +/- 4% in the dog and rat, respectively. A fraction
      of AFPSiA was oxidised to the corresponding sulphonate, (2R)-(3-amino-2
      fluoropropyl)sulphonic acid (AFPSoA) after oral administration to the rat and
      dog. In rat brain membranes, AFPSiA was found to have ten times higher affinity
      for rat brain GABA(B) (K(i) =47 +/- 4.4 nM) compared to GABA(A) (K(i) = 430 +/-
      46 nM) binding sites. The compound was a full agonist at human recombinant
      GABA(B(1a,2)) receptors (EC(50) = 130 +/- 10 nM). In contrast, the metabolite
      AFPSoA was considerably more selective for binding to rat brain GABA(A) (K(i) =
      37 +/- 3.1 nM) vs GABA(B) (K(i) = 6800 +/- 280 nM) receptors. In the mouse, high
      doses (1-8 mmol kg(-1)) of AFPSiA induced a rapid and mild hypothermia followed
      by a profound and sustained hypothermia at the higher doses tested (6 and 8 mmol
      kg(-1)). This effect was unaffected by the selective GABA(B) receptor antagonist
      CGP62349. AFPSoA (1 and 2 mmol kg(-1)) produced transient and moderate
      hypothermia while the hypothermic response was considerably larger at 4 mmol kg(
      1).It is concluded that AFPSiA inhibits but does not abolish TLOSRs in the dog.
      High doses of the compound induce hypothermia in the mouse, which probably is
      attributable to activation of the GABA(A) receptor. The latter effect may be
      caused both by AFPSiA and its oxidised sulphonic acid metabolite AFPSoA.

PMID- 15980876
TI  - Somatostatin at nanomolar concentration reduces collagen I and III synthesis by,
      but not proliferation of activated rat hepatic stellate cells.
AB  - Previous studies have shown antifibrotic effects of somatostatin. Since hepatic
      stellate cells (HSC) express somatostatin receptors and play a key role in
      hepatic fibrogenesis, we investigated the in vitro antifibrotic effect of
      somatostatin on rat HSC. At day 12 after isolation, cells were exposed to
      different concentrations of somatostatin (10(-6)-10(-9) mol l(-1)). mRNA
      expression of collagen types I and III, and of smooth muscle alpha-actin (alpha
      SMA) was analysed by Northern blotting. At 10(-9) mol l(-1), somatostatin
      significantly reduced mRNA expression of collagen I (72.3 +/- 10.7%; 95%
      confidence interval (95% CI): 45.5-99.0), collagen III (79.0 +/- 4.5%; 95% CI:
      67.6-90.4) and alpha-SMA (65.7 +/- 5.9%; 95% CI: 51.1-80.2), as compared to
      control normalized at 100%. These results were confirmed by quantitative RT-PCR.
      Cycloheximide experiments indicated that somatostatin has no direct
      transcriptional effect.Using immunoprecipitation, we demonstrated that
      somatostatin also decreased de novo synthesis of collagen I (73 +/-10%; 95% CI:
      48-98%), collagen III (65 +/- 13%; 95% CI: 33-97%) and alpha-SMA (47 +/- 9%; 95%
      CI: 25-69%). Remarkably, at higher concentrations, somatostatin did not suppress
      collagen mRNA expression nor de novo protein synthesis. We ascribe this
      observation to desensitization of the cells for somatostatin. Cell proliferation,
      as measured by 5-bromo-2'-deoxyuridine labelling, was not altered by
      somatostatin. No significant effect on the intermediate and actin cytoskeleton
      were detected by immunohistochemistry and Western blotting. Our findings imply
      that in vivo antifibrotic effects of somatostatin could result partially from a
      direct action of somatostatin on HSC, but other, in vivo effects are probably
      also involved.

PMID- 15980877
TI  - Topiramate inhibits trigeminovascular activation: an intravital microscopy study.
AB  - Activation, or the altered perception of activation, of trigeminal nerves that
      innervate the cranial vasculature is considered to be a pivotal component of the
      pathophysiology of acute migraine. Calcitonin gene-related peptide (CGRP) levels
      are increased during migraine and after trigeminal nerve stimulation in the cat.
      Both CGRP and nitric oxide (NO) infusion causes headache and delayed migraine in
      migraineurs. Neurogenic stimulation of a cranial window, CGRP and NO injection
      all cause meningeal artery dilation in the rat when viewed using intravital
      microscopy. Topiramate is an antiepileptic drug with established efficacy as a
      migraine preventive, and has recently been shown to inhibit neurons of the
      trigeminocervical complex after superior sagittal sinus stimulation. In this
      study, we used intravital microscopy with neurogenic dural vasodilation, and CGRP
      and NO-induced dilation to examine whether intravenous topiramate has effects on
      the trigeminovascular system. Topiramate was able to attentuate neurogenic dural
      vasodilation maximally after 15 min by 52% at 30 mg kg(-1) (t(5) = 6.78, n = 6);
      there was no significant inhibition at 10 mg kg(-1). There was also significant
      attenuation of the NO-induced dilation maximally after 15 min, at both 10 and 30
      mg kg(-1) by 21% (t(6) = 6.09, n = 7) and 41% (t(6) = 5.3, n = 7), respectively.
      CGRP-induced dilation was not inhibited at either dose of topiramate. The study
      demonstrates that topiramate is likely to inhibit neurogenic dural vasodilation
      by inhibiting the release of CGRP from prejunctional trigeminal neurons, thus
      attenuating the dural vasodilation. Topiramate is not able to act
      postsynaptically at the blood vessels themselves as the CGRP-induced dilation was
      not attenuated. The data are consistent with an effect of topiramate on
      trigeminovascular activation which may form part of its preventive antimigraine
      mechanisms of action.

PMID- 15980879
TI  - Donor lymphocyte infusions can result in sustained remissions in patients with
      residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem
      cell transplantation.
AB  - We treated 17 patients with refractory (n = 7) or relapsed lymphoid malignancy (n
      = 10) following allogeneic HSCT with donor lymphocyte infusions (DLI). Patients
      with low-grade disease received DLI alone (n = 7) or following radiotherapy (n =
      1). Patients with aggressive disease (n = 9) received prior chemotherapy. Nine
      out of 15 patients receiving DLI from sibling donors responded after one (n = 6),
      two (n = 2) and three (n = 1) infusions. Both MUD recipients achieved CR after
      two and three DLI. In all, 10/17 patients achieved CR including 3/4 patients with
      chronic lymphatic leukaemia (CLL), 4/4 with mantle cell lymphoma (MCL), 3/4 with
      follicular NHL but 0/5 with aggressive NHL/Richters. The median CD3 cell dose to
      achieve CR for siblings was 2 x 10(7)/kg. One patient with CLL had a second
      transplant following DLI-induced aplasia and is in CR at 14 months giving a final
      CR rate of 64%. Grade II-IV acute GVHD developed in 45% and chronic GVHD in 8/9
      evaluable patients. Of the 11 patients finally achieving CR, one patient with MCL
      relapsed at 18 months post-DLI but all others remain in remission with a median
      follow-up of 40 months (range 12-64 months). Low-grade NHL and MCL have a high
      response rate and sustained remissions following DLI. Aggressive disease responds
      poorly however, despite pre-DLI chemotherapy.

PMID- 15980880
TI  - Prognostic analysis of pre-transplant peripheral T-cell levels in patients
      receiving an autologous hematopoietic progenitor-cell transplant.
AB  - The purpose of this study was to evaluate pre-transplant T-cell status in
      autologous hematopoietic progenitor-cell transplantation (HPCT) recipients.
      Between 1999 and 2002 we prospectively enrolled 85 autologous HPCT recipients
      with solid tumors (N = 50) or hematological malignancies (n = 35). Patient
      diagnoses included breast cancer (N = 49), non-Hodgkin's lymphoma (N = 20),
      myeloma (N = 11), Hodgkin's disease (N = 3), germ-cell tumor (N = 1) and
      amyloidosis (N = 1). Levels of CD3, CD4, CD8, memory and naive CD4, and CD8 T
      cell subsets were analyzed before autologous HPCT. Autologous HPCT recipients
      presented with lower pre-transplant counts of CD3, CD4, but not CD8 T cells, as
      compared to healthy controls. Pre-transplant CD4 T-cell levels correlated with
      progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P = 0.05),
      in patients with hematologic malignancies (P = 0.02) and breast cancer (P =
      0.04). Specifically, pre-transplant memory CD4 + CD45RA - CD62L - T-cell levels
      correlated with PFS (P = 0.01). The prognostic effects of pre-transplant CD4 and
      CD4 + CD45RA - CD62L - T cells were independent of tumor diagnosis, tumor stage,
      tumor sensitivity, and, for breast cancer patients, Her2 / neu status. Our
      results suggest that pre-transplant CD4 T-cell status, specifically CD4 + CD45RA 
      CD62L - memory T cells, correlates with the outcome of autologous HPCT
      recipients. These observations suggest the feasibility of prospective
      identification of those patients at higher risk of relapse, based on their immune
      status.

PMID- 15980878
TI  - The Quintiles Prize Lecture 2004. The identification of the adenosine A2B
      receptor as a novel therapeutic target in asthma.
AB  - Adenosine is a powerful bronchoconstrictor of asthmatic, but not normal, airways.
      In vitro studies on isolated human mast cells and basophils revealed that
      adenosine and selective analogues augmented inflammatory mediator release from
      mast cells by stimulating A(2) receptors. Pharmacological blockade of mast cell
      mediator release in vivo also attenuated adenosine-induced bronchoconstriction,
      as did theophylline, by adenosine A(2) receptor antagonism. Further in vitro
      studies revealed that the asthmatic response to adenosine is likely to be
      mediated via the A(2B) subtype which is selectively antagonised by enprofylline.
      Studies in animal models, especially mice, have shown a close synergistic
      interaction between adenosine, Th2 and airway remodelling responses. The recent
      description of A(2B) receptors on human airway smooth muscle cells that mediate
      cytokine and chemokine release and induce differentiation of fibroblasts into
      myofibroblasts strengthens the view that adenosine maybe more than an
      inflammatory mediator in asthma but also participates in airway wall remodelling
      in this disease. These data have provided a firm basis for developing adenosine
      A(2B) receptor antagonists as a new therapeutic approach to this disease.

PMID- 15980882
TI  - Successful mobilization of peripheral blood stem cells using recombinant human
      stem cell factor in heavily pretreated patients who have failed a previous
      attempt with a granulocyte colony-stimulating factor-based regimen.
AB  - To assess the efficacy of recombinant human stem cell factor (rHuSCF), 48
      patients who had failed to mobilize >2.0 x 10(6) CD34+ cells/kg with granulocyte
      colony-stimulating factor (G-CSF) (10 microg/kg twice daily) with, or without,
      concomitant chemotherapy (G-CSF-based regimen), were remobilized with the
      addition of rHuSCF (20 microg/kg/day). In all, 18/48 (38%) achieved a total of
      >2.0 x 10(6) CD34+ cells/kg with the second rHuSCF-based mobilisation alone and
      29/48 (60%) achieved a cumulative total of >2.0 x 10(6) CD34+ cells/kg following
      remobilization. Inclusion of chemotherapy in the mobilization regimen resulted in
      a higher yield of CD34+ cells/kg for both the initial G-CSF-based and subsequent
      rHuSCF-based regimens (0.90 vs 0.54, P < 0.01 and 2.36 vs 1.34, P < 0.01,
      respectively). The total peripheral blood stem cells PBSC collected from the G
      CSF-based regimen, performance status, baseline platelet count and albumin were
      significantly associated with successful remobilization. Patients with multiple
      myeloma were also more likely to successfully remobilize. There was no threshold
      of total collected from the failed G-CSF-based regimen below which successful
      remobilization with the rHuSCF-based regimen was not possible. We therefore
      propose a predictive model [PBSC expected = 0.6+(G-CSF-based total collection)+2
      (rHuSCF-based day 1 collection)] to calculate the cumulative total of PBSC
      expected following a maximum of five leukaphereses. This algorithm may permit the
      early identification of patients who are unlikely to achieve sufficient PBSC for
      transplantation and allow physicians to direct the resources involved in PBSC
      collection in a more appropriate and economical manner.

PMID- 15980881
TI  - Granulocyte colony-stimulating factor for poor graft function after allogeneic
      stem cell transplantation: 3 days of G-CSF identifies long-term responders.
AB  - Poor graft function (PGF) is a frequent cause of morbidity after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). To study the value of
      granulocyte colony-stimulating factor (G-CSF) in PGF, we retrospectively analyzed
      81 episodes of PGF in 66 patients transplanted from 01/94 to 01/99 from an HLA
      identical sibling (n = 45) or an unrelated (n = 21) donor. Median age was 29
      years, 55 patients had malignancies. A total of 11 patients received a CD34+
      selected graft. Viral infections (25%), myelotoxic drug (33%), fungal/bacterial
      infections (14%), and GVHD (31%) were present before PGF diagnosis. Median time
      from allo-HSCT to PGF was 75 (25-474) days. All patients were treated with G-CSF.
      In 77/81 episodes, there was a response that was sustained in 57. A total of 27
      patients presented an increase of white cell count (WBC) >0.1 x 10(9)/l after 3
      days of G-CSF. The 5-year survival was 37% and was significantly better in
      patients with increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (65 vs 18%, P <
      0.0001). In multivariate analysis, increased WBC > 0.1 x 10(9)/l after 3 days of
      G-CSF (P = 0.002) was associated with better survival, while BuCy-based
      conditioning (P = 0.02) and GVHD (P = 0.005) were associated with higher risk of
      death. In conclusion, hematological response after 3 days with G-CSF predicted a
      better survival for patients with PGF after allo-SCT.

PMID- 15980883
TI  - Favourable response to antithymocyte globulin therapy in resistant acute graft
      versus-host disease.

PMID- 15980884
TI  - Cell-mediated immune responses to influenza vaccination in healthy volunteers and
      allogeneic stem cell transplant recipients.
AB  - Influenza is one of the most common respiratory diseases in humans. The response
      to vaccination is frequently poor in immunosuppressed individuals. The aim of the
      present study was to develop an enzyme-linked immunospot (ELISPOT) assay for
      measuring of the specific T-cell response to influenza vaccination. In all, 18
      healthy subjects and six stem cell transplantation (SCT) patients tested before
      and 4 weeks after influenza vaccination were included in the present study.
      Peripheral blood lymphocytes were stimulated with four influenza peptides; three
      based on sequences from the hemagglutinin and one from the M1 protein. The
      ELISPOT assay and the measurement of intracellular IFN-gamma production were used
      to determine the cell-mediated responses after stimulation with the peptides.
      Influenza vaccination elicited strong cell-mediated immune responses in the
      healthy controls to all four peptides with 3.2-6.9-fold increases in the number
      of IFN-gamma producing spots/10(6) cells. By intracellular staining, it was
      suggested that CD4+ cells mediated the responses to the hemagglutinin peptides.
      In contrast, there was no increase in the number of IFN-gamma producing cells
      response after vaccination in the six SCT patients. In conclusion, our results
      suggest that the ELISPOT assay might be used as a complement to serology for
      monitoring of future influenza vaccine studies in SCT patients.

PMID- 15980885
TI  - Involvement of cyclin D3 in liver metastasis of colorectal cancer, revealed by
      genome-wide copy-number analysis.
AB  - The question of whether any genetic differences exist between primary and
      colorectal cancers (CRCs) and their metastatic foci is controversial. To look for
      genetic aberrations involved in metastasis of CRCs to the liver, we performed
      subtractive comparative genomic hybridization (CGH) experiments using paired
      samples from 20 CRC patients with primary tumors and synchronous or metachronous
      liver metastases. Relatively frequent gains in DNA copy number were detected at
      6p, suggesting the presence of one or more metastasis-related genes in the
      region. Analysis of 11 CRC cell lines using array-based CGH (CGH-array) revealed
      one 6p candidate gene, CCND3. Quantitative reverse transcriptase-polymerase chain
      reaction experiments showed that CCND3 was significantly upregulated in liver
      metastatic lesions compared with primary lesions (P<0.0152). In addition,
      immunohistochemical analysis of 120 primary CRC tumors demonstrated that cyclin
      D3 expression in the region of rolled edge was significantly associated with
      total recurrence, especially hematogenous recurrence (P=0.0307). The results
      implied involvement of cyclin D3 in liver metastasis of CRC, and the data may
      contribute to the development of a novel therapy or diagnostic agent for this
      currently intractable disease. Our experiments also confirmed the power of
      subtractive CGH and CGH-array analysis for identifying cancer-related genes.

PMID- 15980886
TI  - Use of tissue recombination to predict phenotypes of transgenic mouse models of
      prostate carcinoma.
AB  - Transgenic mouse models of cancer represent a powerful approach for exploring
      disease processes and testing potential therapeutic interventions. Currently, it
      is difficult to predict if a specific genetic manipulation will result in a
      desirable phenotype. The present study tests the idea that tissue recombinants
      recapitulate the pathologic features of the neoplastic prostate seen in
      transgenic mice, and would thus be suitable predictive models for new mouse
      design. The large probasin-large T-antigen (LPB-Tag) transgenic lines 12T-7f and
      12T-10 were used as a basis for this study. Tissue recombinants of bladder
      epithelium (BlE) and urogenital sinus mesenchyme (UGM) were implanted under the
      renal capsule of athymic mice. Recombinants composed of BlE from 12T-10 LPB-Tag
      and wild-type (wt) UGM faithfully recapitulated the histopathologic and temporal
      features of intact transgenic mice of this line. Tissue recombinants using BlE
      from 12T-7f mice and wt UGM developed epithelial proliferation with atypia that
      lacked the associated hypercellular stroma seen in the intact 12T-7f line.
      Recombinants using 12T-7f UGM demonstrated that the hypercellular stroma results
      from stromal cell expression of the SV40 large T antigen. Corresponding to the
      recombinant phenotypes, stromal Tag immunostaining was observed in prostate
      tissues from intact 12T-7f but not 12T-10 mice. Similar stromal expression of Tag
      was also noted in the hypercellular TRAMP prostatic stroma. Further analysis
      revealed a previously unreported pattern of SV40T expression in the LADY and
      TRAMP models including ductus deferens and seminal vesicle stroma as well as
      region and cell type-specific patterns in the epididymis. The present study
      demonstrates the utility of using tissue recombination to explore organ-specific
      phenotypes. Recombination strategies should enable quick and cost-effective
      screening for likely phenotypes in transgenic animals. This comparison of tissue
      recombination to existing models shows that this approach can elicit new
      information on well-characterized models.

PMID- 15980887
TI  - RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors.
AB  - We analyzed RASSF1A and NORE1A methylation and BRAF mutation in 89 thyroid
      tumors, 42 non-neoplastic thyroid tissues and three thyroid tumor cell lines
      using polymerase chain reaction (PCR), methylation-specific PCR, Western blotting
      and DNA sequencing in order to study thyroid tumor pathogenesis and progression.
      RASSF1A promoter methylation was present in all three thyroid cell lines and in
      27/78 (35%) of benign and malignant thyroid tumors. We showed for the first time
      that there was generally good agreement between RASSF1A methylation status and
      RASSF1A protein expression. We also examined for the first time NORE1A promoter
      region methylation in thyroid cell lines and primary tumors and showed that two
      of three thyroid cell lines were methylated in the NORE1A promoter region, while
      all primary thyroid tumors analyzed (n=51) were unmethylated. BRAF mutation was
      present in 38% of papillary thyroid carcinomas (PTC), including 20% of PTC with a
      follicular variant pattern and 67% of the tall cell variant of PTC. Hyalinizing
      trabecular tumors (n=23), which had nuclear features similar to PTC, did not have
      BRAF mutations, indicating that the presence of BRAF mutations can help to
      separate these two tumor types. Phospho-MEK expression was increased in the NPA
      cell line, which had a BRAF mutation, supporting the importance of the BRAF
      pathway alterations in PTC pathogenesis. These results indicate that RASSF1A
      epigenetic changes are an early event in thyroid tumor pathogenesis and
      progression and that NORE1A methylation is uncommon in primary thyroid tumors.
      BRAF mutation occurs later in thyroid tumor progression and is restricted mainly
      to PTC and anaplastic thyroid carcinoma.

PMID- 15980888
TI  - Cell death pathways in retroviral infection.

PMID- 15980889
TI  - Growth rate and oxygen regulate the interactions of group B Streptococcus with
      polarized respiratory epithelial cells.
AB  - We investigated growth conditions that regulate the ability of group B
      Streptococcus (GBS) to attach to, invade, and translocate through polarized human
      respiratory epithelial cells (RECs). GBS grown in a chemostat at a fast cell mass
      doubling time (t(d) = 1.8 h), invaded RECs from both the apical and basolateral
      surfaces in higher numbers compared with those held at a t(d) = 11 h. With the
      exception of adherence from the basolateral surface, GBS reached peak adherence
      to, invasion of, and translocation through RECs when held at the fast t(d) with
      15% dissolved oxygen compared with 0% dissolved oxygen. Growth rate and oxygen
      level strongly influence the interaction of GBS with polarized RECs and likely
      GBS pathogenicity.

PMID- 15980890
TI  - Effect of environmental characteristics on Pythium and Mesocriconema spp. in golf
      course greens in Alabama.
AB  - The role the environment has on populations of Pythium and Mesocriconema spp. was
      investigated at 5 golf course locations in east central Alabama. Every 4 to 5
      weeks soil samples were collected from 3 golf greens on each of the 5 golf
      courses. Environmental data, including air and soil temperature, pH and relative
      humidity, were also collected. Dilution plating and a combined sieving and sugar
      flotation procedure were conducted to determine the populations of Pythium and
      Mesocriconema spp. for each month. Isolates of Pythium from 4 months were also
      identified. Pythium spp. populations increased as soil temperature and ambient
      air temperature prior to sampling decreased (P < 0.05). Pythium spp. populations
      were highest in the winter and lowest in the spring. At some locations,
      populations of Mesocriconema spp. increased as soil acidity and populations of
      Pythium spp. decreased (P < 0.05) and as ambient air temperature prior to
      sampling increased (P < 0.05). Eight species of Pythium were isolated from 4
      months, with Pythium rostratum being the most commonly isolated. Results suggest
      that Pythium and Mesocriconema spp. prefer different soil environments.

PMID- 15980891
TI  - Comparison of 2 ultrafiltration systems for the concentration of seeded viruses
      from environmental waters.
AB  - The use of ultrafiltration as a concentration method to recover viruses from
      environmental waters was investigated. Two ultrafiltration systems (hollow fiber
      and tangential flow) in a large- (100 L) and small-scale (2 L) configuration were
      able to recover greater than 50% of multiple viruses (bacteriophage PP7 and T1
      and poliovirus type 2) from varying water turbidities (10-157 nephelometric
      turbidity units (NTU)) simultaneously. Mean recoveries (n = 3) in ground and
      surface water by the large-scale hollow fiber ultrafiltration system (100 L) were
      comparable to recoveries observed in the small-scale system (2 L). Recovery of
      seeded viruses in highly turbid waters from small-scale tangential flow (2 L)
      (screen and open channel) and hollow fiber ultrafilters (2 L) (small pilot) were
      greater than 70%. Clogging occurred in the hollow fiber pencil module and when
      particulate concentrations exceeded 1.6 g/L and 5.5 g/L (dry mass) in the screen
      and open channel filters, respectively. The small pilot module was able to filter
      all concentrates without clogging. The small pilot hollow fiber ultrafilter was
      used to test recovery of seeded viruses from surface waters from different
      geographical regions in 10-L volumes. Recoveries >70% were observed from all
      locations.

PMID- 15980892
TI  - Proteinase PI and lactococcin A genes are located on the largest plasmid in
      Lactococcus lactis subsp. lactis bv. diacetylactis S50.
AB  - Lactococcus lactis subsp. lactis bv. diacetylactis S50 produces a lactococcin A
      like bacteriocin named bacteriocin S50, and cell envelope-associated PI-type
      proteinase activity. This strain harbours 3 small size plasmids: pS6 (6.3 kb),
      pS7a (7.31 kb), and pS7b (7.27 kb). Plasmid curing using a combination of
      novobiocin treatment (10 microg.mL-1) and sublethal temperature (40 degrees C)
      resulted in a very low yield (0.17%) of Prt-, Bac-, Bacs derivatives, which
      retained all 3 small size resident plasmids. Pulsed-field gel electrophoresis of
      DNA isolated from the strain S50 and cured derivatives in combination with
      restriction enzyme analysis and DNA-DNA hybridization revealed that S50 contains
      2 additional large plasmids: pS140 (140 kb) and pS80 (80 kb). Conjugation
      experiments using strain S50 as a donor and various lactococcal recipients
      resulted in Prt+, Bac+, Bacr transconjugants. Analysis of these transconjugants
      strongly indicated that plasmid pS140 harbours the prt and bac genes encoding
      proteinase and bacteriocin production, and immunity to bacteriocin, since each
      Prt+, Bac+, Bacr tranconjugant contained pS140. Accordingly, none of the Prt-,Bac
      , Bacs transconjugants contained this plasmid. pS140 was a self-transmissible
      conjugative plasmid regardless of the host lactococcal recipient used in the
      test. Frequency of conjugation of plasmid pS140 did not depend on either the
      donor or recipient strain.

PMID- 15980893
TI  - Underrepresentation of short palindromes in Selenomonas ruminantium DNA: evidence
      for horizontal gene transfer of restriction and modification systems?
AB  - Molecular analysis of isolates of the rumen bacterium Selenomonas ruminantium
      revealed a high variety and frequency of site-specific (restriction)
      endonucleases. While all known S. ruminantium restriction and modification
      systems recognize hexanucleotide sequences only, consistently low counts of both
      6-bp and 4-bp palindromes were found in DNA sequences of S. ruminantium.
      Statistical analysis indicated that there is some correlation between the degree
      of underrepresentation of tetranucleotide words and the number of known
      restriction endonucleases for a given sequence. Control analysis showed the same
      correlation in lambda DNA but not in human adenovirus DNA. Based on the data
      presented, it could be proposed that there is a much higher historical occurrence
      of restriction and modification systems in S. ruminantium and (or) frequent
      horizontal gene transfer of restriction and modification gene complexes.

PMID- 15980894
TI  - Conjugation of tetanus toxoid with Salmonella typhimurium PTCC 1735 O-specific
      polysaccharide and its effects on production of opsonizing antibodies in a mouse
      model.
AB  - Serious enteric and extra-intestinal infections with Salmonella typhimurium are
      very common in many human populations. Phagocytosis is the main defense mechanism
      against this bacterium; however, the unique structure of S. typhimurium
      lipopolysaccharide (LPS) makes it resistant to opsonization by complement
      components. In the present study, the S. typhimurium LPS O-chain was purified and
      conjugated with tetanus toxoid and the effects of the conjugated vaccine (O
      specific polysaccharide tetanus toxoid (O-SP-TT)) on induction of specific
      antibodies were investigated in a mouse model. In vitro assays measuring
      phagocytosis in the presence of opsonizing antibodies were performed. Three
      subcutaneous injections of the O-SP-TT conjugate conferred protection against the
      intraperitoneal challenge with S. typhimurium and the LD50 was greater for
      immunized animals than for controls. The mean number of ingested S. typhimirium /
      mouse peritoneal cell in the presence of sera obtained from immunized mice with
      purified O-chain, O-SP-TT conjugate, heat-killed bacteria, and negative control
      were 6.96, 14.24, 15.96, and 6.67, respectively. In summary, we developed an O-SP
      TT conjugate that induced opsonizing antibodies that increased phagocytosis, as
      determined by in vitro assays. In addition, chemiluminescence results, an
      indicator of oxidative burst, indicated that peritoneal cells respond better to
      live S. typhimurium cells in the presence of sera obtained from O-SP-TT conjugate
      immunized mice.

PMID- 15980895
TI  - Phylogenetic assessment of heterotrophic bacteria from a water distribution
      system using 16S rDNA sequencing.
AB  - Determination of a heterotrophic plate count (HPC) for drinking-water samples
      alone is not enough to assess possible health hazards associated with sudden
      changes in the bacterial count. Speciation is very crucial to determine whether
      the population includes pathogens and (or) opportunistic pathogens. Most of the
      isolates recovered from drinking water samples could not be allocated to a
      specific phylogenetic branch based on the use of conventional diagnostic methods.
      The present study had to use phylogenetic analysis, which was simplified by
      determining and using the first 500-bp sequence of the 16S rDNA, to successfully
      identify the type and species of bacteria found in the samples. Gram-positive
      bacteria alpha-, beta-, and gamma-Proteobacteria were found to be the major
      groups representing the heterotrophic bacteria in drinking water. The study also
      revealed that the presence of sphingomonads in drinking water supplies may be
      much more common than has been reported so far and thus further studies are
      merited. The intermittent mode of supply, mainly characterized by water
      stagnation and flow interruption associated possibly with biofilm detachment,
      raised the possibility that the studied bacterial populations in such systems
      represented organisms coming from 2 different niches, the biofilm and the water
      column.

PMID- 15980896
TI  - Diversity of organophosphorus pesticide-degrading bacteria in a polluted soil and
      conservation of their organophosphorus hydrolase genes.
AB  - Seven methyl parathion-degrading bacteria were isolated from a long-term methyl
      parathion contaminated soil and were found to belong to the genera
      Pseudaminobacter, Achromobacter, Brucella, and Ochrobactrum. Southern blot
      analysis using an mpd gene probe revealed that their hydrolase genes were similar
      to the mpd gene from Plesiomonas sp. strain M6 and were all located on the
      chromosome. Gene libraries were constructed from genomic DNA of each of the 7
      organophosphorus pesticide-degrading bacteria, and their mpd genes were cloned
      and sequenced. Sequence analysis revealed that their hydrolase genes were
      conserved, and that the G+C content of the mpd genes were distinctly different
      from that of the chromosome-located 16S rRNA gene, suggesting that the mpd gene
      could be transferred and expressed among a variety of bacterial hosts.

PMID- 15980897
TI  - Effectiveness of 3 antagonistic bacterial isolates to control Rhizoctonia solani
      Kuhn on lettuce and potato.
AB  - Rhizoctonia solani causes yield losses in numerous economically important
      European crops. To develop a biocontrol strategy, 3 potato-associated ecto- and
      endophytically living bacterial strains Pseudomonas fluorescens B1, Pseudomonas
      fluorescens B2, and Serratia plymuthica B4 were evaluated against R. solani in
      potato and in lettuce. The disease-suppression effect of the 3 biocontrol agents
      (BCAs) was tested in a growth chamber and in the field. In growth chamber
      experiments, all 3 BCAs completely or significantly limited the dry mass (DM)
      losses on lettuce and the disease severity (DS) caused by R. solani on potato
      sprouts. Strain B1 showed the highest suppression effect (52% on average) on
      potato. Under field conditions, the DS on both crops, which were bacterized,
      decreased significantly, and the biomass losses on lettuce decreased
      significantly as well. The greatest disease-suppression effect on potato was
      achieved by strain B1 (37%), followed by B2 (33%) and then B4 (31%), whereas the
      marketable tuber yield increased up to 12% (B1), 6% (B2), and 17% (B4) compared
      with the pathogen control at higher disease pressure. Furthermore, in all
      experiments, B1 proved to be the most effective BCA against R. solani. Therefore,
      this BCA could be a candidate for developing a commercial product against
      Rhizoctonia diseases. To our knowledge, this is the first report on the high
      potential of endophytes to be used as a biological control agent against R.
      solani under field conditions.

PMID- 15980898
TI  - Endometriosis-induced acute small and large bowel obstruction: rare clinical
      entities.
AB  - The extragonadal manifestations of intestinal endometriosis necessitating
      immediate abdominal surgical exploration are, to date, sparsely represented
      within the literature. We present two cases of acute complete small and large
      bowel obstruction secondary to endometriosis, requiring emergent laparotomy; and
      review the pertinent literature.

PMID- 15980899
TI  - Biliary peritonitis due to fistulous tract rupture following a T-tube removal.
AB  - We present a patient with biliary peritonitis following a T-tube removal. The
      patient underwent laparotomy; a rupture of the fistulous tract around the T-tube
      was found. A Nelaton catheter was inserted through this opening and advanced
      toward the biliary tree and secured in place by a suture ligature. Postoperative
      course was uneventful.

PMID- 15980900
TI  - Rectus sheath haematoma (RSH) mimicking acute intra-abdominal pathology.
AB  - AIM: Rectus sheath haematoma (RSH) is a rare cause of acute abdomen. We present a
      case series of patients seen at Wanganui Hospital, North Island, New Zealand.
      METHODS: A retrospective survey of patients developing RSH over a 2-year period
      (from 2002 to 2004) in our hospital was carried out. RESULTS: Seven patients were
      identified with RSH (male:female ratio=6:1, age range=16-80 years). Six of the
      RSH were spontaneous and four out of these six were on anticoagulant therapy post
      acute coronary event. Each presented with acute abdomen and all were missed on
      initial evaluation. Two were diagnosed initially as bowel obstruction, one as
      acute diverticulitis, one as incarcerated hernia, one as an ovarian mass, and
      another as non-specific abdominal pain. One patient had traumatic RSH with
      peritonitis secondary to accompanying jejunal perforation. The ultrasound pick-up
      rate was 50% of but computed tomography (CT) abdomen was 100% diagnostic. Five
      (70%) had a significant fall in haematocrit, requiring blood transfusion. All
      settled on conservative management, with one requiring admission to intensive
      care. CONCLUSION: Clinical diagnosis of RSH is unreliable. CT imaging is the
      procedure of choice and should be promptly carried out especially in those on
      anticoagulant therapy for early diagnosis and proper management.

PMID- 15980901
TI  - PHARMAC responds to the RMI's editorial.

PMID- 15980902
TI  - Benzbromarone therapy in management of refractory gout.
AB  - AIM: To assess the efficacy and safety of benzbromarone in patients with renal
      impairment and severe tophaceous gout (despite receiving optimal conventional
      therapy). METHODS: Six patients with refractory gout (despite optimal therapy)
      were treated with benzbromarone. Uric acid levels and number of gout attacks were
      recorded monthly. Adverse events to medications were also recorded. RESULTS:
      After 1 year of treatment with benzbromarone, average uric acid level reduced
      from 0.61 mmol/L to 0.46 mmol/L. Repeated measures tests on the changes in uric
      acid were clinically significant (p=0.01). The frequency of acute attacks of gout
      was reduced from 16 (8-20) to 7.3 (1-16); p=0.01. None of the patients reported
      adverse events with the medications. There were no acute flares resulting from
      initiation of medications. CONCLUSION: Benzbromarone is effective in lowering
      uric acid levels and in reducing the number of acute attacks of gout in patients
      who have failed optimal treatment. Making this drug more readily available will
      increase our therapeutic choices for urate reduction and help decrease the
      morbidity associated with gout.

PMID- 15980903
TI  - Maxillofacial fractures at Waikato Hospital, New Zealand: 1989 to 2000.
AB  - AIM: To describe the patterns of facial fractures presenting to a tertiary
      referral centre in New Zealand, and to identify risk indicators for maxillofacial
      trauma. METHOD: Clinical records of 2527 patients referred to a tertiary base
      hospital for the treatment of maxillofacial fractures from 1989 to 2000 were
      retrospectively analysed. Age, sex, ethnicity, cause of injury, anatomic location
      of facial fractures, alcohol involvement, and treatment received were recorded.
      RESULTS: The number of facial fractures treated by the Maxillofacial Unit at
      Waikato Hospital annually almost doubled over the 12-year study period (1989 to
      2000). Eighty percent of those presenting with maxillofacial injuries were male,
      and 40% were aged between 15 and 24 years. Interpersonal violence and road
      traffic accidents were the most frequent causes of facial fractures. Alcohol
      consumption was associated with just over one-third of all cases, and was
      strongly associated with interpersonal violence. CONCLUSION: Presentation of
      patients with facial fractures at the Maxillofacial and Oral Surgery Unit at
      Waikato Hospital almost doubled over the 12 years. Risk indicators for
      presentation with a maxillofacial fracture included male gender, alcohol
      consumption, and interpersonal violence. There is an urgent need for appropriate
      health promotion to reduce interpersonal violence.

PMID- 15980904
TI  - Are snowboarders more likely to damage their spines than skiers? Lessons learned
      from a study of spinal injuries from the Otago skifields in New Zealand.
AB  - AIMS: The aim of this study was to determine the incidence, nature, and
      circumstances of spinal injuries caused by skiing and snowboarding at the Otago
      skifields and treated at Dunedin Hospital during the period 1991 to 2002.
      METHODS: Patients were identified from the audit records of the Department of
      Orthopaedic Surgery at Dunedin Hospital. RESULTS: Twenty-five cases were included
      in the study, 18 snowboarders, and 7 skiers. Twenty-two cases had spinal
      fractures, with skiers having a higher proportion of burst fractures and multiple
      fractures. The most frequently fractured vertebrae were T12 and L1, and wedge
      fractures were the most common fracture type. Jump-related activities were the
      most common cause of injury in snowboarders, in contrast to skiers whose injuries
      were more commonly fall-related. CONCLUSIONS: Skier-related spinal injuries were
      rare and sporadic over the study period, whereas snowboarder-related spinal
      injuries were more frequent and more recent in occurrence.

PMID- 15980905
TI  - Non-resident orthopaedic admissions to Dunedin Hospital, New Zealand: 1997 to
      2004.
AB  - AIMS: The purpose of this study is to audit the numbers of non-residents
      requiring orthopaedic admission to our hospital and determine the effect of
      increasing tourist numbers and changes in Accident ACC regulations on healthcare
      resources. METHODS: Details of non-resident orthopaedic admissions for fiscal
      years 1997/8 to 2003/4 were analysed with respect to country of residence,
      mechanism of injury, case weights consumed, and actual costs. RESULTS: There has
      been no change in numbers of admissions or cost, averaging 32 cases (50 case
      weights [CWs]) per year. Most patients came from Asia (59 cases; 26%), then
      Australia (52 cases; 23%) and UK (40 cases; 18%). Snowsports accounted for 40% of
      admissions, Motor vehicle accidents (MVA) for 17%, and falls for 29%. Non
      resident, non-MVA admissions have averaged 21 CWs per year since the changes in
      ACC regulations in 1999. DISCUSSION: Despite increasing tourist numbers, there
      has been no increase in numbers or CW of non-residents requiring orthopaedic
      admission. Although representing only a small proportion of the orthopaedic
      budget, they generate many hidden costs. The 50 CWs annually equates to
      approximately 13 major joint replacements per year. The increase in CWs consumed
      due to the ACC changes have had no corresponding increase in contracted
      orthopaedic volumes.

PMID- 15980906
TI  - Liver transplantation for hepatocellular carcinoma in New Zealand: a prospective
      intent-to-treat analysis.
AB  - Liver transplantation (LT) is potentially curative for early hepatocellular
      carcinoma (HCC) but time spent on the waiting list exposes patients to the risk
      of tumour progression prior to transplantation. AIMS: We prospectively evaluated
      the outcome for New Zealand patients listed for LT with a pre-transplant
      diagnosis of HCC. METHODS: Patients with 1 to 3 tumours, up to 5 cm in diameter,
      and no vascular invasion or extra-hepatic disease on imaging, were considered
      eligible for LT. The results were analysed by intention to treat from the time of
      listing. RESULTS: Fifty-nine patients were listed with a pre-transplant diagnosis
      of HCC between February 1998 and June 2004. Ten (17%) were de-listed before LT
      because of tumour progression, and 9 of 45 (20%) who underwent LT have
      experienced tumour recurrence up to 59 months post-transplant. For patients
      listed with a diagnosis of HCC, 5-year actuarial survival was 56.1% from the time
      of listing. For those listed and transplanted with a diagnosis of HCC, 5-year
      actuarial survival from the time of transplant was 63.5%. This is significantly
      worse than the 89.8% 5-year survival for patients transplanted without HCC over
      the same period (p=0.018) and this difference was entirely due to tumour
      recurrence. CONCLUSIONS: 37% of patients listed according to our criteria were
      either de-listed due to tumour progression or experienced recurrence after LT.
      Based on this experience strategies aimed at preventing waiting list drop out
      have been adopted, however expansion of tumour-related selection criteria cannot
      be recommended without a concomitant increase in donor organ availability.

PMID- 15980907
TI  - Optimal management of chronic gout: attempting to render the (t)issues crystal
      clear.

PMID- 15980908
TI  - Angry young men, interpersonal violence, alcohol, and broken faces.

PMID- 15980909
TI  - Endometriosis: a gynaecological and colorectal disease.

PMID- 15980910
TI  - Quality use of medicines activities: QSUM and PHARMAC.

PMID- 15980912
TI  - Postnatal exercise: the mother's wellbeing is important too.

PMID- 15980913
TI  - Animal and vegetable fats, and Coronary Heart Disease.

PMID- 15980914
TI  - Response to Maubach and Hoek's paper on GP attitudes to DTCA.

PMID- 15980915
TI  - PHARMAC and tobacco control in New Zealand: two licensed funded options are
      already available.

PMID- 15980916
TI  - Prenatal testing for aneuploidy in New Zealand: time for action.

PMID- 15980917
TI  - Medical image. A big sack.

PMID- 15980918
TI  - Adolescent aggression and differentiation of self: guided mindfulness meditation
      in the service of individuation.
AB  - This paper presents adolescent aggression as mediated by the level of
      differentiation of self. No research has directly addressed Bowen's notion that
      level of differentiation impacts child functioning including aggression. Level of
      differentiation is discussed in conjunction with social, gender and cultural
      norms as manifested in aggressive behavior. Female adolescent aggression is
      described as mainly relationship focused and expressed via verbal threats,
      intimidation and manipulation, while male aggression is described mainly as overt
      physical violence involving dominance and competitiveness. Research on
      differentiation focuses mainly on Western cultures that tend to be
      individualistic. Jewish-Israeli society is in transition from collectivistic to
      individualistic cultural values in the midst of ongoing hostilities. These
      processes create conflict regarding togetherness and individuality needs among
      adolescents, who are exposed to contradictory messages regarding separating and
      staying close. External as well as internal expressions of aggression
      (depression, suicide) are presented as coping strategies in the service of a
      wounded self-negotiating with the world. Guided mindfulness meditation is a
      powerful technique for facilitating healing and growth toward autonomy by helping
      adolescents connect to their inner voice. This technique may be especially useful
      in the adolescent search for self-awareness, meaning and life purpose. Bodily,
      cognitive and emotional experiences are treated as informative regarding the
      'self' and facilitate expansion of self-perception and individuality.

PMID- 15980919
TI  - Interaction effect between phosphorus and zinc on their availability in soil in
      relation to their contents in stevia (Stevia rebaudiana).
AB  - A greenhouse experiment was conducted at the Indian Institute of Horticultural
      Research (IIHR), Bangalore to study the interaction effect between phosphorus and
      zinc on their availability in soil in relation to their contents in stevia
      (Stevia rebaudiana). The results show that the amount of available P and Zn
      content in soil has been found to increase initially and, thereafter, the amount
      of the same decreased with the progress of plant growth up to 60 days
      irrespective of treatments. The amount of P and Zn in soils showed an increase
      with their separate applications either as soil or foliar spray while that of the
      same value significantly decreased both in soils and plants due to their combined
      applications, suggesting a mutual antagonistic effect between Zn and P affecting
      each other's availability in soil and content in the stevia plant.

PMID- 15980920
TI  - Development of the Chinese nutrition screen (CNS) for use in institutional
      settings.
AB  - OBJECTIVES: To develop and validate a nutritional screening tool (CNS) for
      elderly Chinese subjects in the institutional setting. DESIGN: Using the MNA as a
      guide, a questionnaire was developed appropriate for the Chinese health care
      system, diet, food customs and culture, using physician assessment for
      comparison. PARTICIPANTS: 200 men and 200 women aged 65 years or older,
      approximately equally distributed by age between two cities in China (Hong Kong
      and Shanghai), were recruited from hospitals and old age homes for the
      reliability study. 340 men and 527 women were recruited for the validity study.
      RESULTS: The CNS compared with physician assessments based on two groups, normal
      or at risk with less than normal nutritional status, had kappa coefficients of
      0.5 overall and were as high as 0.8 in Shanghai. CNS was able to identify about
      90% of all persons with normal nutritional status and had about a 60% chance of
      correctly identifying a person at risk with a less than normal nutritional
      status. CONCLUSION: The CNS can be used in a 2-group classification to identify
      those who have a normal nutritional status (CNS > or = 21). Those who do not fall
      into this group should have their nutritional status evaluated in greater detail
      (CNS score < or = 20). The applicability of screening tools may vary depending on
      the site and the population characteristics.

PMID- 15980921
TI  - Relationship between MNA and SF-36 in a free-living elderly population aged 70 to
      75.
AB  - BACKGROUND: Within a larger study of social network and nutrition, we
      investigated measurements of nutritional status and health related quality of
      life. OBJECTIVE: To relate a well-established questionnaire of nutritional status
      (MNA) to a likewise well-established questionnaire of health related quality of
      life (SF-36) in community dwelling, free-living and, healthy 70-75 years old
      persons. DESIGN: Before an interview, the MNA and SF-36 questionnaires were
      filled in by 128 participants from a sample of 262 subjects. RESULTS: The MNA
      worked well as a measurement in this sample. Many MNA aspects correlated with the
      SF-36 scales. The correlations between MNA total score and the eight SF-36 scales
      varied from .27 to .62. DISCUSSION: This correlation was partly due to the fact
      that MNA has questions of health but also to the fact that there is an empirical
      relation between nutrition and health. CONCLUSION: The MNA measurement is
      applicable to a healthy, free-living elderly population and parts of the MNA can
      be interpreted as measurements of health related quality of life. Low values of
      SF-36 could also be used as predictors of risk of malnutrition, although further
      studies are required to confirm this result.

PMID- 15980922
TI  - Screening for malnutrition in elderly acute medical patients: the usefulness of
      MNA-SF.
AB  - BACKGROUND: Malnutrition is often over-seen in elderly acute medical patients. It
      is a need for a simple and robust screening tool. OBJECTIVE: The aim was to
      evaluate, with regard to validity, the Mini Nutritional Assessment-Short Form
      (MNA-SF) as a screening tool for malnutrition in elderly acute medical patients.
      DESIGN: This is an observational study where a nurse's scoring of MNA-SF is
      compared to comprehensive assessment by a clinical nutritionist (gold standard).
      Sixty-nine patients aged 70 years and older and admitted to a general medical
      department in year 2000 and 2001 were included. RESULTS: The mean MNA-SF score
      was 7.8 (SD +/- 2.88, range 2 to 12). Fifty-one patients (74%) scored positive
      for malnutrition or risk of malnutrition (MNA-SF < 11), whereas only 21 (30%)
      were scored to have malnutrition by the nutritionist. Sensitivity of the MNA-SF
      was 1.0 and specificity 0.38, giving 0.57 correctly classified subjects. Best
      subset logistic regression showed BMI < 23 to be the only item explaining the
      gold standard. When using BMI < 23, 32 (46%) subjects screened positive for
      malnutrition (sensitivity 0.86, specificity 0.71), giving 0.75 correctly
      classified subjects. CONCLUSIONS: When screening elderly acute medical patients
      in general wards for malnutrition or risk of malnutrition, the MNA-SF have a high
      sensitivity and can be useful. The sole use of BMI < 23 may be equally effective,
      but will give no information leading towards an explanation. We recommend that a
      score of BM < 23 should be followed by MNA-SF when the aim is to identify poor
      nutritional status in elderly acute medical patients.

PMID- 15980923
TI  - U.S. Food Guide Pyramid food group intake by Asian Indian immigrants in the U.S.
AB  - This study examined the food group intake and the dietary quality of middle-aged
      and older Gujarati Asian Indian immigrants (45 years or older) living in two
      urban metropolitan areas in the U.S. Participants (90 men, 99 females) completed
      a 24-hour dietary recall, which was used to determine if they met the daily food
      group intake guidelines of the U.S. Food Guide Pyramid. The overall quality of
      their reported dietary intake was determined using the Healthy Eating Index based
      on their nutrient and food group intake. Both men and women met the daily number
      of servings recommendations for the grains (men: 9.3 servings/day; women: 6.9
      servings/day) and vegetables (men: 4.5 servings/day; women: 3.6 servings/day)
      groups, but did not meet the recommendations for fruits, dairy and meats groups.
      The total score on the Healthy Eating Index of the diets of these participants
      was 73, indicative of a dietary intake that does not meet the established U.S.
      dietary guidelines. These immigrants should be educated about appropriate food
      choices (ethnic and non-ethnic) within each of the U.S. Food Guide Pyramid food
      groups to improve the overall quality of their dietary intakes.

PMID- 15980924
TI  - Where to find omega-3 fatty acids and how feeding animals with diet enriched in
      omega-3 fatty acids to increase nutritional value of derived products for human:
      what is actually useful ?
AB  - Omega-3 polyunsaturated fatty acids have two major field of interest. The first
      lies in their quantitative abundance and their role in the development and
      maintenance of the brain. The second is their role in the prevention of different
      pathologies, mainly the cardiovascular diseases, and more lately some psychiatric
      disorders, from stress to depression and dementia. Thus, dietary omega-3 fatty
      acids are very important to ensure brain structure and function, more
      specifically during development and aging. However, concerning essential alpha
      linolenic acid (ALA), most occidental diets contain about 50 % of the recommended
      dietary allowances. The problem is to know which foods are naturally rich in this
      fatty acid, and to determine the true impact of the formulations (enriched in
      omega-3 fatty acids, either ALA or EPA and DHA) in chows used on farms and
      breeding centres on the nutritional value of the products (meat, butter, milk and
      dairy products, cheese, and eggs, etc), and thus their effect on the health of
      consumers, especially to ensure adequate quantities in the diet of the aging
      people. The consequences (qualitative and quantitative) of modifications in the
      composition of animal foods on the value of derived products consumed by humans
      are more marked when single-stomach animals are concerned than multi-stomach
      animals. Because, for example, hydrogenating intestinal bacteria of the latter
      group transform a large proportion of polyunsaturated fatty acids in their food
      into saturated fatty acids, among others, thus depriving them of any biological
      interest. Under the best conditions, by feeding animals with extracts of linseed
      and rapeseed grains for example, the level of ALA acid is increased approximately
      two-fold in beef and six-fold in pork, ten-fold in chicken, and forty-fold in
      eggs. By feeding animals with fish extracts or algae (oils) the level of DHA is
      increased about 2-fold in beef, 7-fold in chicken, 6-fold in eggs, and 20-fold in
      fish (salmon). To obtain such results, it is sufficient to respect only the
      physiological needs of the animal, which was generally the case with traditional
      methods. It is important to stress the role of fish, whose nutritional value for
      humans in terms of lipids (determined by omega-3 fatty acid levels) can vary
      considerably according to the type of fats the animals have been fed. The aim of
      preventing some aspects of cardiovascular disease (and other pathologies) can be
      achieved, or on the contrary frustrated, depending on the nature of fatty acids
      present in fish flesh, the direct consequence of the nature of fats with which
      they have been fed. It is the same for eggs, "omega- 3 eggs" being in fact
      similar to natural eggs, were used in the formulation of certain formula milks
      for infants, whose composition was closest to that of breast milk. In fact, the
      additional cost on the price paid by the consumer is modest compared to the
      considerable gain in nutritional value in terms of omega-3 fatty acids content.
      Interestingly, in aged people, ALA recommendations in France are increased (0.8%
      daily energy intake in adult, 0.9 % in aged) and DHA is multiplied by 2 (0.05 %
      daily energy intake in adult, 0.1 % in aged; as well as in pregnant and lactating
      women).

PMID- 15980925
TI  - Nutritional status in cognitively intact older people receiving home care
      services--a pilot study.
AB  - Older adults are a potentially vulnerable group for malnutrition. This cross
      sectional pilot study aims to assess the nutritional status of elderly patients
      living at home and receiving home health care services. The data were collected
      from patient care plans, the Mini Nutritional Assessment (MNA), and a
      questionnaire on eating problems. In addition, serum nutritional status
      indicators were measured, and an oral examination including quantitative saliva
      measurement was carried out. Out of 71 eligible patients 51 (72%) patients aged
      76-93 years participated. MNA results showed that 47% were at risk of
      malnutrition. Care plans for 26 patients made reference to questions of nutrition
      but provided no detailed forward planning. The mean serum albumin value was 39.1
      +/- 3.8 g/l, seven patients had a value lower than 35 g/l. MNA scores were
      significantly lower for female patients with haemoglobin values lower than 120
      g/l (p = 0.027). The dentist's estimation of dry mouth and subjective problems in
      energy intake were significantly associated with lower MNA scores (p = 0.049 and
      p = 0.015). Subjects with functioning natural dentition had higher body mass
      index (BMI) scores than others (p = 0.0485). The results point at the importance
      of using screening tools such as the MNA for purposes of nutritional assessment,
      the estimation of oral problems such as dry mouth, chewing and swallowing
      problems, and advance planning in nutritional issues within the field of home
      care.

PMID- 15980926
TI  - Survival after percutaneous endoscopic gastrostomy: the role of dementia.
AB  - BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) is a widely used technique
      for enteral feeding in nursing home patients. Several factors including
      malnutrition, hypoalbuminemia, older age, number of co-morbidities and cognitive
      impairment adversely affect survival. OBJECTIVE: This study evaluated the
      relative impact of age, serum albumin, number of co-morbid illnesses and dementia
      on survival in male nursing home patients who had undergone percutaneous
      endoscopic gastrostomy (PEG). DESIGN: In a retrospective study the hospital
      records of all North Chicago Veterans Affair (VA) male nursing home residents
      (n=88) who had PEG placed between 1990 through 2000 were reviewed. Of the 88
      charts reviewed, 17 were eliminated from analysis due to incomplete data.
      Following data was examined: Age, serum albumin, number of co-morbid illnesses,
      presence of dementia, survival in years following PEG placement. RESULTS:
      Advancing age was associated with increasing probability of dementia and
      increased number of co-morbidities. Post PEG survival decreased with increasing
      age, with lower serum albumin, and increased number of co-morbidities. Age and
      serum albumin were strong predictors of survival in PEG recipients without the
      diagnosis of dementia. However, in PEG recipients with a diagnosis of dementia,
      age and serum albumin no longer predicted survival. Dementia appears to attenuate
      the effects of age and serum albumin on survival following PEG placement.
      CONCLUSION: In the presence of dementia, none of the usual predictors of survival
      in PEG recipients remain significant.

PMID- 15980927
TI  - The SOLINUT study: analysis of the interaction between nutrition and loneliness
      in persons aged over 70 years.
AB  - BACKGROUND: Insufficient nutritional status is a frequent problem in the elderly,
      correlated with aging, diseases, but also environmental factors in this growing
      part of the population. Loneliness should be one of these factors. OBJECTIVE AND
      DESIGN: the aim of the SOLINUT study was to determine the relationship between
      loneliness and nutritional status in persons aged over 70 years, in order to
      improve the detection and management of the isolated elderly at high risk of
      malnutrition. It was both an epidemiological and cross-sectional anthropological
      study, based on quantitative and qualitative nutritional and sociological
      investigation, carried out between March 2002 and May 2003 in 150 elderly persons
      (mean age 80.8 years, oldest subject 99 years) living alone at home. RESULTS: a
      large number of subjects had a dietary intake which was inadequate to cover their
      nutritional needs--42.6% less than 25 kcal/kg/day, threshold for undernutrition
      in the elderly--21.3% had established undernutrition, ( average in
      epidemiological studies in non isolated elderly populations: 3-7%)--44% were not
      able to carry a shopping bag weighing 5 kg and so could not buy their own food.
      Lastly, 32% never shared a meal with family or friends, which reveals their
      degree of social isolation. CONCLUSION: It has been demonstrated that greater
      coordination between the various service providers would prevent a large number
      of isolated persons from failing to obtain the various allocations and services
      available to them. We must stress the extreme importance of preemptive
      intervention, by an active screening policy which could simultaneously prevent
      undernutrition and encourage physical activity in isolated persons to avoid their
      becoming "excluded recluses".

PMID- 15980928
TI  - The Middle-East Academy for Medicine of Ageing.
AB  - The first session of the Middle-East Academy for Medicine of Ageing, the MEAMA,
      started with a focus on demographic aspects in the region and the problems the
      participants meet in their own countries related to the services for health
      related problems in older people. Also several medical topics were discussed. The
      MEAMA uses the methods of the EAMA, which have been proven to be attractive for
      participants and speakers. In the discussions the question was raised how to
      start the process to develop and enhance the services. It was suggested to start
      with the organization of national societies and interact with neighbouring
      countries before presenting measures needed at the national level. The MEAMA
      might be an excellent forum for the discussion how to stimulate the development
      of the services for older people in the Middle-East area.

PMID- 15980929
TI  - Risk factors for acute myocardial infarction among Okinawans.
AB  - PURPOSE: Okinawa is well known as the leading area for longevity and people in
      Okinawan islands are known to have the lowest risk of ischemic heart disease
      (IHD). Reasons for this particularly low IHD risk among Okinawans are unclear.
      Since most studies about IHD risk factors have been based on population in
      Western nations and their findings may not apply to Okinawans, a hospital-based
      case-control study was conducted at a community hospital in Okinawa. METHODS: To
      assess the relative importance of risk factors for IHD among the people in
      Okinawa, 205 Okinawan patients who had acute myocardial infarction (AMI) and 205
      age-and-gender matched control were analyzed. RESULTS: The most important risk
      factor of AMI was current cigarette smoking. History of diabetes mellitus and
      hypertension were also independent risk factors. Of lipid profile, lower
      concentrations of serum high density lipoprotein (HDL) cholesterol and higher
      serum triglyceride (TG) were independent risk factors while, in contrary, serum
      low density lipoprotein cholesterol and uric acid were not associated with AMI.
      CONCLUSIONS: To effectively prevent IHD among Okinawans, smoking cessation and
      treatment of hypertension, diabetes, and dyslipidemia (high TG and low HDL) are
      important. However, lowering LDL cholesterol may be not.

PMID- 15980930
TI  - Straining at stool and stool frequency in free-living and institutionalised older
      adults.
AB  - BACKGROUND: The diagnosis of functional constipation according to Rome II
      criteria includes assessment of straining. However the prevalence in older adults
      is unknown. AIMS: To assess the prevalence of straining and its association with
      stool frequency in free-living (FL) and institutionalised (INS) older adults.
      METHODS: 50 FL subjects (mean age 74 years, range (65-97), 42% male) and 42 INS
      subjects (mean age 84 years, range (69-101) 36% male) were recruited. Stool
      frequency and straining to start and to finish were prospectively recorded by
      subjects for 7 consecutive days in a bowel habit diary. Statistical analyses were
      performed using the Chi-square or the Pearson correlation coefficient as
      appropriate. RESULTS: The mean stool frequency (n/week) was significantly higher
      (p <0.001) in the FL group compared with the INS group (11.7 and 4.9
      respectively). The percentage of subjects experiencing straining to start on more
      than 25% of occasions was significantly lower in the FL compared with the INS
      group (34% and 64% respectively, chi2 = 8.4, p = 0.004, df = 1). The percentage
      of subjects experiencing straining to finish on more than 25% of occasions was
      significantly lower in the FL compared with the INS group (16% and 41%
      respectively, chi2 = 6.9, p = 0.009, df = 1). CONCLUSIONS: FL subjects had
      significantly higher stool frequency and had to strain passing a stool (to start
      and to finish) less often than their INS counterparts. Moreover, straining to
      start was experienced more often than straining to finish in both groups.

PMID- 15980931
TI  - The effect of supplementation with an enriched drink on indices of immune
      function in frail elderly.
AB  - Ageing induces a change in immune responses. Besides this, impaired nutritional
      status is considered to have a critical influence on immune function, which may
      be reversed by nutritional supplementation. We evaluated the effect of an
      enriched drink on immune function in the elderly. 33 frail elderly subjects (aged
      > or = 65 years and body mass index < or = 25) received two 125 ml packages of
      either an enriched drink (n=20) or placebo (n=13) daily for 6 months. The
      enriched drink contained macro- and micronutrients. At baseline and after 6
      months blood samples were drawn and PBMC's were isolated. ConA stimulated
      proliferation and IL-2 production of PBMC's were measured. There was a
      significant difference between groups in proliferation over the study period. The
      supplement group remained stable whereas the placebo group showed a reduction in
      proliferation over the 6-month period. There was no significant difference in IL
      2 production between groups. Our study adds to the evidence that nutritional
      supplementation can affect immune function in the elderly.

PMID- 15980932
TI  - Autonomy and appropriate care for older disabled older people: guidelines of the
      Swiss Academy of Medical Sciences: commentary.

PMID- 15980933
TI  - Smaller but energy and protein-enriched meals improve energy and nutrient intakes
      in elderly patients.
AB  - The purpose of the present study was to investigate if smaller but energy and
      protein enriched meals could improve energy and nutrient intakes in elderly
      geriatric patients. Ten patients, between 77 and 87 years of age were included in
      the study, performed at a Geriatric rehabilitation ward. The first week after
      inclusion, the patients were offered a three days' standard hospital menu and the
      second week, a three days' energy and protein-enriched menu. The consumption of
      food and the fluid intake were recorded using a pre-coded food record book during
      both the menus and analysed by the Swedish National Food Administration. The
      patients' energy requirements were calculated according to the Nordic Nutrition
      Recommendation for elderly subjects. When the standard hospital menu was offered,
      six patients had lower energy intake, -67 to -674 kcal/day, than the calculated
      energy requirements. The daily energy intake increased by 37 %, with the energy
      and protein-enriched menu compared with the standard hospital menu. Furthermore,
      the daily intake of protein, fat, carbohydrate, certain vitamins and minerals was
      significantly higher with the energy and protein-enriched menu compared with the
      standard hospital menu. CONCLUSION: This study showed that the intake of energy
      and nutrients increased with the energy and protein-enriched menu in elderly
      patients on a geriatric rehabilitation ward.

PMID- 15980934
TI  - Efficacy of salmon calcitonin in complex regional pain syndrome (type 1) in
      addition to physical therapy.
AB  - The aim of the study was to assess the efficacy of salmon calcitonin, which was
      suggested as effective in the treatment of complex regional pain syndrome type 1
      (CRPS 1). Patients who had suffered trauma to their upper extremities and
      developed CRPS 1 were included into this randomised, controlled single-blind
      study. The diagnosis was made according to the clinical examination and
      scintigraphy. The evaluation parameters were: pain [visual analogue scale (VAS)],
      the angle of dorsiflexion (DF) and palmar flexion (PF) of the wrist, distance
      between the fingertip and distal palmar crease (FT-DPC), allodynia, hyperalgesia
      and trophic changes. One group received paracetamol 1500 m/day and the other
      group salmon calcitonin 200 IU/day for 2 months. All of the patients participated
      in a physical therapy and exercise programme. A total of 35 patients were divided
      into two groups, who were found to be similar for age, body mass index, period of
      trauma, period of rest in a plaster splint or bandage, the duration of symptoms,
      VAS, DF and PF angle, FT-DPC, presence of allodynia, hyperalgesia and trophic
      changes (p>0.05). The control examination showed similar results for allodynia,
      hyperalgesia and trophic changes, whereas remarkable improvement was observed in
      the rest of the parameters within groups. On the other hand, between the two
      groups there was no significant difference in any of the parameters (p>0.05) This
      randomised, single-blind study showed that all of the patients with acute CRPS 1
      in their upper extremities after trauma, who were treated with either paracetamol
      or calcitonin along with physical therapy, recovered in all parameters
      significantly, but without any difference between groups. We can conclude that
      calcitonin does not make any favourable contribution in the treatment of patients
      with acute CRPS 1; physical therapy combined with only a simple analgesic is an
      efficient means of therapy.

PMID- 15980936
TI  - ANCA-associated large vessel compromise.

PMID- 15980935
TI  - Lupus arthropathy: a case series of patients with rhupus.
AB  - Among the clinical manifestations of systemic lupus erythematosus (SLE) is an
      arthropathy, which is usually nonerosive. In many cases the joint involvement is
      mild. A subset of patients have deforming, nonerosive Jaccoud's arthropathy, and
      a minority have an arthropathy with clinical findings similar to rheumatoid
      arthritis (RA) that has been called "rhupus." We report our series of eight
      patients (seven female, one male) with rhupus arthropathy. Patients were between
      the ages of 17 and 38 years (average: 30.3 years) at disease onset. All had
      deforming or Jaccoud's arthropathy, and three had erosive disease. The arthritis
      was typically the first disease manifestation. Other symptoms of lupus including
      vasculitis and glomerulonephritis appeared after an average of 2.8 years. All had
      positive antinuclear antibody and rheumatoid factor. Rhupus arthritis is not a
      combination of RA and SLE, but should be regarded as a variant of the arthropathy
      of lupus.

PMID- 15980937
TI  - A case of Sjogren's syndrome with acute transverse myelitis and polyneuropathy in
      a patient free of sicca symptoms.
AB  - Acute transverse myelitis (ATM) is an inflammatory process involving a restricted
      area of the spinal cord. The usually dramatic presentation with rapidly
      progressive symptoms involving motor, sensory, and autonomic functions makes ATM
      a medical emergency. ATM has been cited as a rare and unusual complication of
      Sjogren's syndrome, but early diagnosis and aggressive treatment might improve
      the prognosis. I report a case of Sjogren's syndrome with ATM and polyneuropathy
      in a patient free of sicca symptoms and having skin lesions and synovitis as the
      initial manifestations.

PMID- 15980938
TI  - Memory after menopause: preliminary considerations of hormone influence on
      cognitive functioning.
AB  - Oestrogen has been shown to have a wide variety of organisational and activating
      effects on brain structure and function. Despite the significant amount of
      research investigating the relation and effects of oestrogen to cognitive
      performance in menopausal women over the past two decades, studies have failed to
      produce consistent findings. This paper reports on evaluations of eighty-one
      community-based postmenopausal Australian women comparing current, past and never
      users of hormone therapy (HT) on a wide range of cognitive measures of general,
      verbal and visual memory, delayed recall, attention, concentration and verbal
      comprehension. Few significant differences were found among the three groups in
      the demographic profile, health status or psychological functioning. Although
      never users had significantly lower scores on verbal memory than past users, the
      differences were not statistically significant when adjustments were made
      controlling for age, education level, verbal comprehension, attention and
      concentration. These findings challenge long-held beliefs regarding the
      usefulness of oestrogen supplements as a protective factor against cognitive
      decline in older women's later years.

PMID- 15980939
TI  - Microbial community in a geothermal aquifer associated with the subsurface of the
      Great Artesian Basin, Australia.
AB  - To investigate the biomass and phylogenetic diversity of the microbial community
      inhabiting the deep aquifer of the Great Artesian Basin (GAB), geothermal
      groundwater gushing out from the aquifer was sampled and analyzed. Microbial
      cells in the groundwater were stained with acridine orange and directly counted
      by epifluorescence microscopy. Microbial cells were present at a density of 10(8)
      10(9) cells per liter of groundwater. Archaeal and bacterial small-subunit rRNA
      genes (rDNAs) were amplified by PCR with Archaea- and Bacteria-specific primer
      sets, and clone libraries were constructed separately. A total of 59 clones were
      analyzed in archaeal and bacterial 16S rDNA libraries, respectively. The archaeal
      16S rDNA clones were divided into nine operated taxonomic units (OTUs) by
      restriction fragment length polymorphism. These OTUs were closely related to the
      methanogenic genera Methanospirillum and Methanosaeta, the heterotrophic genus
      Thermoplasma, or miscellaneous crenarchaeota group. More than one-half of the
      archaeal clones (59% of total 59 clones) were placed beside phylogenetic clusters
      of methanogens. The majority of the methanogen-related clones (83%) was closely
      related to a group of hydrogenotrophic methanogens (genus Methanospirillum). The
      bacterial OTUs branched into seven phylogenetic clusters related to hydrogen
      oxidizing thermophiles in the genera Hydrogenobacter and Hydrogenophilus, a
      sulfate-reducing thermophile in the genus Thermodesulfovibrio, chemoheterotropic
      bacteria in the genera Thermus and Aquaspirillum, or the candidate division OP10.
      Clones closely related to the thermophilic hydrogen-oxidizers in the genera
      Hydrogenobacter and Hydrogenophilus were dominant in the bacterial clone library
      (37% of a total of 59 clones). The dominancy of hydrogen-users strongly suggested
      that H(2) plays an important role as a primary substrate in the microbial
      ecosystem of this deep geothermal aquifer.

PMID- 15980940
TI  - The Mrp system: a giant among monovalent cation/proton antiporters?
AB  - Mrp systems are a novel and broadly distributed type of monovalent cation/proton
      antiporter of bacteria and archaea. Monovalent cation/proton antiporters are
      membrane transport proteins that catalyze efflux of cytoplasmic sodium, potassium
      or lithium ions in exchange for external hydrogen ions (protons). Other known
      monovalent cation antiporters are single gene products, whereas Mrp systems have
      been proposed to function as hetero-oligomers. A mrp operon typically has six or
      seven genes encoding hydrophobic proteins all of which are required for optimal
      Mrp-dependent sodium-resistance. There is little sequence similarity of Mrp
      proteins to other antiporters but three of these proteins have significant
      sequence similarity to membrane embedded subunits of ion-translocating electron
      transport complexes. Mrp antiporters have essential roles in the physiology of
      alkaliphilic and neutralophilic Bacillus species, nitrogen-fixing Sinorhizobium
      meliloti and in the pathogen Staphylococcus aureus, although these bacteria
      contain multiple monovalent cation/proton antiporters. The wide distribution of
      Mrp systems leads to the anticipation of important roles in an even wider variety
      of pathogens, extremophiles and environmentally important organisms. Here, the
      distribution, established physiological roles and catalytic activities of Mrp
      systems are reviewed, hypotheses regarding their complexity are discussed and
      major open questions about their function are highlighted.

PMID- 15980942
TI  - Recapitulation of kidney development paradigms by BMP-7 reverses chronic renal
      injury.

PMID- 15980941
TI  - Renal tubular transport and the genetic basis of hypertensive disease.
AB  - Several monogenic hypertensive disorders are caused by genetic mutations leading
      to the deranged function and/or regulation of renal tubular NaCl transport, such
      as mutations of the renal epithelial Na+ channel (ENaC) in Liddle syndrome, of
      the kinase WNK1 (with no K) in Gordon syndrome, and of the mineralocorticoid
      receptor, or of 11beta-hydroxysteroid dehydrogenase. Moreover, excessive
      formation of aldosterone in glucocorticoid-remediable hypertension leads to
      severe hypertension. Conversely, impaired function of the Na+,K+,2Cl-
      cotransporter (NKCC2), the renal outer medullary K+ channel (ROMK1), and the
      renal epithelial Cl- channel ClCKb/Barttin causes Bartter syndrome and defective
      Na+,Cl+ cotransporter (NCCT) Gitelman syndrome, salt-wasting disorders with
      hypotension. These monogenic disorders are rare, but illustrate the significance
      of renal tubular transport in blood pressure regulation. There is little doubt,
      however, that deranged renal salt reabsorption significantly contributes to
      essential hypertension polymorphisms of several genes participating in the
      regulation of renal Na+ transport have been shown to be associated with blood
      pressure and prevalence of hypertension. Two common genes will be discussed in
      more detail. The first encodes the renal Cl- channel ClCKb. A gain-of-function
      mutation of ClCKb, increasing channel activity by 7- to 20-fold is found in
      approximately 20% of unselected Caucasians and 40% of an unselected African
      population. The second common gene variant (prevalence, 3%-5% in unselected
      Caucasians), to be discussed in more detail, affects the serum and glucocorticoid
      inducible kinase SGK1, a kinase upregulated by mineralocorticoids and enhancing
      the activity of ENaC, ROMK, and Na+/K+ATPase. Both gene variants are associated
      with slightly increased blood pressure. SGK1 further stimulates the glucose
      transporter SGLT1, and the SGK1 gene variant correlates, in addition, with
      increased body mass index.

PMID- 15980944
TI  - Connective tissue growth factor mediates the profibrotic effects of transforming
      growth factor-beta produced by tubular epithelial cells in response to high
      glucose.
AB  - BACKGROUND: It was reported that connective tissue growth factor (CTGF) was
      expressed in the tubular epithelial cells of the diabetic kidney. CTGF has, among
      other factors, been implicated in mediating the downstream, profibrotic effects
      of transforming growth factor-beta (TGF-beta), though is precise role in
      interstitial fibrogenesis in the diabetic kidney has not yet been clarified.
      METHODS: We employed a coculture system involving cultured murine proximal
      tubular epithelial cells (mProx24) and renal fibroblasts (TFB), as a model of the
      subepithelial mesenchyme in the kidney in order to examine the profibrotic
      effects of CTGF derived from mProx24 cells in response to high glucose (30 mM).
      RESULTS: We showed that glucose stimulated CTGF expression in cultured mProx24 in
      both a dose- and a time-dependent manner, and that this effect was mediated by
      increased levels of TGF-beta. We also found that high glucose significantly
      stimulated TFB cells to produce profibrotic molecules, such as type I collagen,
      the EIIIA isoform of fibronectin, and plasminogen activator inhibitor-1. The
      induction of these molecules was both direct and indirect, the latter induction
      being mediated by mProx24 cell-derived CTGF, which, in turn, was induced by TGF
      beta that was produced by the mProx24 cells. CONCLUSIONS: CTGF plays an important
      role in mediating renal interstitial fibrogenesis in response to high glucose
      and, as such, is a reasonable target for anti-fibrotic therapy.

PMID- 15980945
TI  - The Na+-excreting efficacy of indapamide in combination with furosemide in
      massive edema.
AB  - BACKGROUND: Massive systemic edema is often observed in patients with severe
      nephrotic syndrome, including diabetic nephropathy. Although furosemide, a loop
      diuretic, is often administered to these patients, some patients do not respond
      to this treatment, still showing massive edema. METHODS: The efficacy of
      indapamide which has a thiazide-like effect on distal convoluted tubules in
      combination with furosemide, was evaluated in eight patients with massive edema,
      in regard to both Na+ excretion and diuresis. Indapamide 2 mg was administered
      once a day, in the morning, to patients in whom it was considered that furosemide
      treatment of 40-120 mg a day for 1 week was ineffective. RESULTS: Urinary Na+
      excretion was markedly increased, from 83.7 +/- 82.2 mEq/day to 140.7 +/- 33.8
      mEq/day after 1 week of the combination therapy compared with furosemide alone (P
      < 0.01); urine volume was also increased, from 1070 +/- 230 ml to 1359 +/- 296 ml
      after 1 week of the combination therapy (P < 0.05). In this context, body weight
      was significantly decreased, from 57.2 +/- 12.3 kg to 53.4 +/- 12.8 kg, after the
      combination therapy (P = 0.01). Indapamide in combination with furosemide was
      well tolerated, and no significant changes in serum levels of creatinine and
      potassium were observed. CONCLUSIONS: This combination therapy appears to be
      effective in patients with massive edema, as it increased diuresis, and achieved
      potent Na+ excretion.

PMID- 15980943
TI  - Glomerular function reserve and sodium sensitivity.
AB  - In clinical nephrology, the glomerular filtration rate (GFR) has been recognized
      as the golden standard to assess renal function. However, a normal GFR does not
      necessarily mean normal filtration capability of the kidneys, because impaired
      filtration capability can be compensated for by elevating glomerular hydraulic
      pressure. Therefore, an early phase of glomerular dysfunction cannot be detected
      by the baseline GFR alone. On the other hand, glomerular capillary hypertension
      is widely recognized as one of the strong risk factors for the progression of
      nephropathies. Now, it is very important to imagine glomerular hemodynamics in
      each patient with nephropathy for detecting early dysfunction, as well as for
      evaluating risk factors. Here, I would like to summarize the current status of
      how an early phase of renal dysfunction can be detected in clinical practice. I
      truly anticipate that new methods to assess glomerular hemodynamics in humans
      will be developed in the near future.

PMID- 15980946
TI  - Glutathione peroxidase activity in patients with renal disorders.
AB  - BACKGROUND: Glutathione peroxidase (GPx) protects cells from oxidative damage by
      catalyzing the reduction of both organic and hydrogen peroxides, using
      glutathione as a reducing agent. Both plasma GPx (P-GPx) and erythrocyte GPx (E
      GPx) have been identified in human blood. Kidney proximal tubular cells are the
      main source of GPx activity in the plasma. Oxidative damage has been reported to
      participate in the progression and complications of renal diseases. METHODS: The
      activities of both E-GPx and P-GPx were determined, using Randox commercial kits,
      in 12 patients with nephrotic syndrome (NS), 48 patients with renal impairment
      (RI), and 50 patients with chronic renal failure on maintenance hemodialysis (HD;
      before as well as immediately after dialysis), and in 50 healthy volunteers who
      served as controls. RESULTS: Compared to the results in healthy controls, P-GPx
      activity was reduced in the HD group and the RI group, whereas the NS group
      showed no significant difference from the control. The HD group showed a higher
      drop in P-GPx (reduced to 36.6% of the mean control value) than the RI group
      (reduced to 61.8% of the mean control value). Further analysis of the RI group
      showed a highly significant negative correlation between P-GPx activity and serum
      creatinine level (r = -0.691; P < 0.001). Also, a highly significant negative
      correlation was found between P-GPx and blood urea nitrogen (r = -0.792; P <
      0.001). However, E-GPx activity showed no significant correlation with either
      serum creatinine or blood urea nitrogen. E-GPx was reduced to 55.2% and 68.9% of
      the mean control 1 value in the NS group and the RI group respectively, while the
      HD group showed no significant change. Further analysis of the RI group found
      that E-GPx activity showed no significant correlation with either serum
      creatinine or blood urea nitrogen. In HD patients, GPx activity was measured
      before and immediately after hemodialysis. E-GPx activity was similar before and
      after dialysis, without a significant difference (pre-dialysis, 37.7 +/- 13.5 U/g
      hemoglobin [Hb]; post-dialysis, 38.72 +/- 12.31 U/g Hb). However, P-GPx activity
      was significantly increased (pre-dialysis, 254.4 +/- 62.6 U/ml; post-dialysis,
      296.98 +/- 74.04 U/ml; P < 0.001), but it was still significantly lower when
      compared to that in the healthy controls. CONCLUSIONS: P-GPx activity is an
      important test to assess the oxidative damage in patients with kidney diseases.
      The progression of renal disorders is accompanied by a decrease in P-GPx
      activity, but not by a decrease in E-GPx activity. Thus, we conclude that P-GPx
      activity largely depends on physiological renal function, whereas E-GPx activity
      does not.

PMID- 15980947
TI  - Prevalence of human polyoma virus (BK virus and JC virus) infection in patients
      with chronic renal disease.
AB  - BACKGROUND: Polyoma virus infection in renal transplant patients is sometimes
      critical in graft survival. But, to date, polyoma virus infection or reactivation
      has not been checked before renal transplantation. The prevalence of polyoma
      viruses (BK virus and JC virus) was investigated in 45 patients with renal
      disease who were future candidates as renal graft recipients. METHODS: Because
      these viruses are excreted in urine, the urine of these 45 patients was analyzed
      by polymerase chain reaction (PCR). The urine of 37 age-matched normal subjects
      (control group) was also investigated. RESULTS: In the control group, 13.5% of
      the normal subjects were positive for BK virus and 24.3% were positive for JC
      virus. In the patients with renal disease, 33.3% were positive for BK virus and
      33.3% were positive for JC virus; the prevalence of BK virus infection was
      significantly higher than that in the normal subjects. Patients with renal
      disease with corticosteroid therapy revealed an especially high prevalence of BK
      virus infection (55.6%), indicating the possibility of viral reactivation by
      corticosteroid therapy. CONCLUSIONS: More attention should be paid to polyoma
      virus infection in candidates for renal transplantation with a previous
      therapeutic history of corticosteroid administration.

PMID- 15980948
TI  - Cardiovascular complications caused by advanced secondary hyperparathyroidism in
      chronic dialysis patients; special focus on dilated cardiomyopathy.
AB  - BACKGROUND: The frequency and prognosis of dilated cardiomyopathy (DCM) caused by
      secondary hyperparathyroidism (2 degrees HPT) is not known. The purpose of this
      study was to determine the morbidity of DCM caused by 2 degrees HPT and the
      efficacy of parathyroidectomy (PTx) in chronic dialysis patients with advanced 2
      degrees HPT was analyzed prospectively. METHODS: Between November 2000 and
      January 2003, 237 dialysis patients who underwent total PTx with forearm
      autograft at our department were enrolled in this study. Cardiac complications
      that existed before PTx were examined. Ten patients (4%) had DCM without valvular
      disease (VD) or ischemic heart disease (IHD). In these 10 patients with DCM
      before operation, we estimated left ventricular (LV) function at 6 months after
      PTx, according to echocardiography findings and clinical symptoms. RESULTS: Six
      months after PTx, left ventricular ejection fraction (LVEF) in these 10 patients
      was significantly improved, from 31.0 +/- 9.8% before PTx, to 56.8 +/- 13.5% (P =
      0.0003), and left ventricular end-diastolic dimension (LVDd) was reduced, from
      59.8 +/- 9.7 mm to 46.3 +/- 7.0 mm (P = 0.0014). The symptoms due to DCM and the
      fall of blood pressure that had occurred during dialysis were clearly improved
      after PTx. CONCLUSIONS: Advanced 2 degrees HPT can influence LV function, and in
      patients who suffered from DCM, LV function was dramatically improved by PTx. PTx
      should be performed immediately in patients with DCM caused by 2 degrees HPT.

PMID- 15980949
TI  - Pretreatment plasma intact parathyroid hormone and serum calcium levels, but not
      serum phosphate levels, predict the response to maxacalcitol therapy in dialysis
      patients with secondary hyperparathyroidism.
AB  - BACKGROUND: The treatment strategy for secondary hyperparathyroidism is generally
      determined empirically with regards to present parathyroid function and serum
      calcium (Ca) and inorganic phosphate (Pi) levels. More evidence is needed to
      avoid the aimless continuation of active vitamin D therapy. METHODS: Nondiabetic
      dialysis patients whose plasma intact parathyroid hormone (iPTH) levels were
      greater than 300 pg/ml were included in the study. Maxacalcitol was intravenously
      injected three times a week. The treatment was continued for 48 weeks, unless the
      iPTH level was reduced to less than 300 pg/ml or unfavorable events occurred. The
      patients whose plasma iPTH levels were below 300 pg/ml within 48 weeks were
      defined as those who had been successfully treated. RESULTS: Findings for 146
      patients were analyzed, and 96 patients were successfully treated. Serum Pi
      levels did not significantly increase during the therapy. The pretreatment plasma
      iPTH levels and serum Ca levels were lower in the patients who were successfully
      treated with maxacalcitol. A logistic regression study and classifying by stratum
      analyses revealed that the pretreatment serum Ca levels and plasma iPTH levels
      were significantly related to the result of maxacalcitol therapy, while the serum
      Pi levels were not. Analyses using a receiver-operating characteristic curve
      revealed that the areas under curves obtained for iPTH and Ca were significantly
      greater than those obtained for Pi (P < 0.0001). CONCLUSIONS: Serum Ca levels and
      parathyroid function were correlated with the results of maxacalcitol therapy.
      Pretreatment serum Pi levels could not predict the result.

PMID- 15980950
TI  - Risk factors for encapsulating peritoneal sclerosis in patients who have
      experienced peritoneal dialysis treatment.
AB  - BACKGROUND: The present study was conducted to clarify the clinical risk factors
      related to the development of encapsulating peritoneal sclerosis (EPS), which is
      one of the most serious complications in patients undergoing peritoneal dialysis
      (PD). METHODS: The records of 78 patients with a history of PD treatment,
      including 18 with EPS, were retrospectively analyzed (male/female, 51:27; age,
      51.8 +/- 11.0 years; PD treatment, 94.1 +/- 42.7 months). The inclusion criteria
      were: duration of PD more than 24 months; 36-month follow up after
      discontinuation of PD; available data for dialysate-to-plasma creatinine ratio
      (D/P Cr), by fast peritoneal equilibration test within 3 months before PD
      discontinuation; and absence of EPS at PD discontinuation. Analytical parameters
      included age, sex, underlying renal disease, duration of PD, membrane transport
      state (higher transporter or lower transporter: D/P cr ratio more than or less
      than 0.75), number of episodes of peritonitis during PD treatment, performance of
      peritoneal lavage after PD discontinuation, and reasons for PD withdrawal
      (ultrafiltration failure, acute peritonitis, social matters). RESULTS:
      Significant differences were noted regarding the PD duration, D/P cr, higher
      membrane transport state, and number of peritonitis episodes during PD. On
      receiver operating characteristic curves, the cutoff points for EPS were: D/P cr
      ratio, 0.74; number of peritonitis episodes, 2; and PD duration (months), 115.2.
      Multivariate analysis, employing the factors age, PD duration, higher membrane
      transport state, and number of peritonitis episodes, which were selected by
      stepwise analysis, identified the latter two factors as significant for the
      development of EPS (odds ratio [OR], 4.0; P = 0.046 and OR, 12.0; P = 0.049,
      respectively). CONCLUSIONS: A higher transporter membrane state and the number of
      peritonitis episodes are factors contributing to the occurrence of EPS in
      patients who have experienced PD treatment.

PMID- 15980951
TI  - Effects of low dialysate calcium concentration on health-related quality of life
      in hemodialysis patients.
AB  - BACKGROUND: A dialysate calcium concentration of 2.5 meq/l (1.25 mmol/l) is
      currently recommended, but there are not enough studies to examine the effects of
      this calcium concentration on clinical outcomes. We explored the effects of this
      calcium concentration on health-related quality of life (HRQOL) in hemodialysis
      patients. METHODS: The dialysate calcium concentration was lowered from 3.0 meq/l
      to 2.5 meq/l in 78 hemodialysis patients. The Medical Outcomes Study (MOS) Short
      Form 36 (SF-36) norm-based scores, the doses of recombinant human erythropoietin
      (rHuEpo), and the serum levels of corrected calcium, phosphorus, intact
      parathyroid hormone (i-PTH), and hemoglobin were compared at baseline and 8
      months after the change of dialysate calcium concentration. RESULTS: Seventy
      three patients completed the study. Mean changes in SF-36 scores were: physical
      functioning, -2.4; role physical, -3.9; bodily pain, -3.4; general health
      perception, -1.5; vitality, -2.2; social functioning, -1.9; role emotional, -2.0;
      mental health, -2.0. The declines of scores for role physical and bodily pain
      were significant. Serum i-PTH levels increased significantly, from 212 pg/ml to
      278 pg/ml, while the doses of rHuEpo and serum levels of corrected calcium,
      phosphorus, and hemoglobin did not change significantly. CONCLUSIONS: A dialysate
      calcium concentration of 2.5 meq/l was not shown to have positive effects on
      HRQOL.

PMID- 15980952
TI  - High iron storage levels are associated with increased DNA oxidative injury in
      patients on regular hemodialysis.
AB  - BACKGROUND: Accumulating evidence suggests that oxidative stress is enhanced in
      patients on regular hemodialysis (HD). Iron supplementation is essential for the
      treatment of renal anemia, but there is a possibility that it could enhance
      oxidative stress by inducing the Fenton reaction. Here, we report our
      investigation of the relation between iron storage and DNA oxidative injury in HD
      patients. METHODS: The study subjects were 48 patients on regular HD (age, 62.7
      +/- 12.1 years; HD duration, 67.2 +/- 62.5 months; non-diabetic/diabetic; 22:26).
      Patients who were positive for hepatitis C virus antibody (HCV Ab), or hepatitis
      B surface antigen (HBsAg), and those with inflammatory or malignant diseases were
      excluded. The serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) level, a marker of DNA
      oxidative injury, was measured before the first HD session of the week in all
      patients, and factors associated with high serum 8-OHdG were investigated. In 9
      patients with a serum ferritin level of more than 1000 ng/ml at study entry,
      serum 8-OHdG levels were followed up for 6 months in the absence of iron
      supplementation. RESULTS: Multivariate analysis showed that the serum ferritin
      level was a significant and independent determinant of serum 8-OHdG, and serum
      ferritin correlated significantly with the total dose of iron supplementation
      during the 6-month period of the study. In the nine patients, without iron
      supplementation, serum 8-OHdG levels, as well as serum ferritin, decreased
      significantly during follow-up. CONCLUSIONS: Our results suggest that increased
      iron storage may induce DNA oxidative injury in patients on regular HD, and that
      the serum ferritin level is a surrogate marker for this pathological condition.

PMID- 15980953
TI  - Post-transplant diabetes mellitus: risk factors, frequency of transplant
      rejections, and long-term prognosis.
AB  - BACKGROUND: Estimates of the incidence of new-onset diabetes after renal
      transplantation vary between 2% and 54%. It was the aim of the present trial to
      study the prevalence of post-transplant diabetes mellitus (DM), the risk factors,
      the frequency of transplant rejections, and the long-term prognosis. METHODS: We
      studied all consecutive patients with endstage renal disease, but without DM who
      received kidney transplantation at our center since 1992 (n = 253; age, 52.2 +/-
      12.6 years; body mass index, 22.0 +/- 7.9 kg/m2). Follow up was 3.3 +/- 1.6 years
      (range, 0.1-17.7) years. RESULTS: In total, 43/253 patients (17%) developed new
      onset DM after transplantation. Patients with new-onset diabetes were
      significantly older (58.3 +/- 11.4 vs 50.9 +/- 12.5 years; P < 0.01) and had a
      tendency to a higher body mass index (24.0 +/- 8.5 vs 21.6 +/- 7.8 kg/m2; P =
      0.077). There were no differences between the groups in respect of blood pressure
      control (137.7 +/- 19.0/81.8 +/- 14.2 vs 137.1 +/- 21.9/83.9 +/- 13.1 mmHg; P =
      0.89/0.39), glomerular filtration rate (58.0 +/- 28.1 vs 64.1 +/- 22.1 ml/min per
      1.73 m2; P = 0.13), steroid dosage (4.5 +/- 1.2 [n = 21] vs 4.6 +/- 2.2 [n = 135]
      mg/day; P = 0.13), or the frequency and dosage of immunosuppressive drugs such as
      cyclosporine, tacrolimus, and sirolimus during the follow up. However, more
      patients with post-transplant diabetes received steroids (83.7% vs 64.3%; P =
      0.021) and azathioprine (41.9% vs 24.3%; P = 0.030). Patients with new-onset
      diabetes had higher serum creatinine values (163.4 +/- 67.9 vs 138.7 +/- 59.5
      micromol/l; P = 0.017). The mean hemoglobin (Hb)A1c in patients with DM was 6.28
      +/- 1.29% (Tosho HPLC; mean normal, 5.15%). In 18 patients (7.1%) transplant
      rejections occurred (16 patients without DM [7.6%] vs 2 patients with new-onset
      DM [4.7%]; P = 0.39). On performing multivariate analysis, the only parameter
      found to be associated with new-onset DM was the body mass index (R2 = 0.05; beta
      = 0.23; P = 0.02), and the only factor associated with transplant rejection was
      fasting blood glucose (R2 = 0.07; beta = 0.28; P = 0.02). None of the other
      parameters included in the models (age, duration after transplantation, diabetes
      duration, immunosuppressive therapy, HbA1c, HLA mismatches) showed any
      associations. CONCLUSIONS: The prevalence of new-onset DM after renal
      transplantation was 17%. The most important parameter associated with new-onset
      diabetes was a higher body mass index, and the most important parameter
      associated with transplant rejection was an elevated fasting blood glucose level.
      To prevent transplant rejections and to improve patients' outcome, in addition to
      providing optimal immunosuppressive therapy and HLA matching, good blood pressure
      control and HbA1c, but also near normal fasting blood glucose levels, should be
      achieved.

PMID- 15980954
TI  - Asymptomatic renal infarction, due to fibromuscular dysplasia, in a young woman
      with 11 years of follow-up.
AB  - We report a 27-year-old woman with renovascular hypertension, renal infarction,
      and hepatic artery aneurysm due to fibromuscular dysplasia. The patient was first
      noted to have renal artery aneurysm and hepatic artery aneurysm at the age of 17.
      The renal infarction was asymptomatic and was incidentally detected by magnetic
      resonance imaging (MRI) examination. Because of the rather peripheral location of
      the aneurysms, percutaneous transluminal renal artery angioplasty was considered
      inappropriate. This case suggests the need for long-term and periodical follow-up
      of patients with fibromuscular dysplasia.

PMID- 15980955
TI  - ANCA-negative pauci-immune crescentic glomerulonephritis complicated with
      recurrent massive gastrointestinal hemorrhage.
AB  - On April 25, 2003, a 62-year-old Japanese man had been admitted to a hospital
      because of heavy proteinuria and elevated serum creatinine level, and purpura on
      the lower extremities. On May 15, 2003, he was referred to our hospital for
      evaluation and treatment. Serum immunoglobulin and complements were within normal
      ranges. Immune serology was negative for antinuclear antibody, antiglomerular
      basement membrane antibody, and antineutrophil cytoplasmic antibodies.
      Histological examination of a percutaneous renal biopsy specimen revealed that
      all of the glomeruli had severe crescent formation without deposits of
      immunoreactants. A diagnosis of antineutrophil cytoplasmic antibody-negative
      pauci-immune crescentic glomerulonephritis was made. The patient was treated with
      one cycle of steroid pulse therapy (1000 mg methylprednisolone daily, given on 3
      consecutive days), and subsequently with prednisolone (60 mg/day). Despite this
      treatment, renal failure progressed rapidly and hemodialysis was started 1 month
      after the acute presentation. On May 30, 2003, he suddenly developed massive
      hematochezia. A technetium-targeted red-blood-cell scan suggested bleeding in the
      small intestine. On June 11, he presented with massive melena. A bleeding ulcer
      was found in the third part of the duodenum, and was treated successfully with
      endoscopy, using a heater probe. On June 19, he presented with massive
      hematochezia again. Mesenteric angiography revealed active bleeding from the
      iliac branch of the superior mesenteric artery. He was treated with continuous
      intraarterial vasopressin infusion by a catheter seated in the branch artery. The
      majority of patients with pauci-immune crescentic glomerulonephritis, one of the
      most common causes of rapidly progressive glomerulonephritis, have glomerular
      disease as part of a systemic vasculitis. Massive gastrointestinal bleeding,
      although rare, should be considered one of the serious complications in these
      patients.

PMID- 15980956
TI  - Tuberous sclerosis, associated with renal cell carcinoma and angiomyolipoma, in a
      patient who developed endstage renal failure after nephrectomy.
AB  - We report a case of tuberous sclerosis (TSC) associated with renal cell carcinoma
      and angiomyolipoma in a patient, who developed endstage renal failure that
      required hemodialysis after nephrectomy. A 37-year-old woman with TSC was
      admitted for further investigation of bilateral renal masses detected by computed
      tomography (CT). Angiography revealed a tumor stain (4 cm in diameter) in the
      medial portion of the right kidney. Because renal cell carcinoma (RCC) was
      strongly suspected, right nephrectomy was performed. Her serum creatinine level
      was already increased, moderately, at 2.4 mg/dl, before the right nephrectomy.
      Her renal function deteriorated quickly (in 1(1/2) years) after the right
      nephrectomy, and hemodialysis was introduced the next year. The histological
      findings of the resected right kidney revealed marked intimal thickening of the
      intralobular arteries. These findings suggested that the renal function loss was
      not only caused by the nephron mass reduction due to the nephrectomy but was also
      caused by nephrosclerosis. Though most patients with TSC die before developing
      endstage renal failure, this patient is currently receiving maintenance
      hemodialysis and has been followed for 3 years with no recurrence of RCC in the
      left kidney.

PMID- 15980957
TI  - Phylogenetic analysis of eukaryotic thiolases suggests multiple proteobacterial
      origins.
AB  - Eukaryotic thiolases are essential enzymes located in three different
      compartments (peroxisome, mitochondrion, and cytosol) that can display catabolic
      or anabolic functions. They are responsible for the thiolytic cleavage of
      oxidized acyl-CoA (thiolase I; EC 2.3.1.16) and the synthesis or degradation of
      acetoacetyl-CoA (thiolase II; EC 2.3.1.9). Phylogenetic analysis of eukaryotic
      thiolase sequences showed that they form six distinct clusters, one of them
      highly divergent, which are in good correlation with their class and subcellular
      location. When analyzed together with a representative sample of prokaryotic
      thiolases, all eukaryotic thiolase groups emerged close to proteobacterial
      sequences. Metazoan cytosolic thiolase II was related to alpha-proteobacterial
      sequences, suggesting a mitochondrial origin. Unexpectedly, cytosolic thiolases
      from green plants and fungi as well as at least one member of all eukaryotic
      peroxisomal and mitochondrial thiolases had delta-proteobacteria as closest
      relatives. Our analysis suggests that these eukaryotic peroxisomal and
      mitochondrial thiolases may have been acquired from delta-proteobacteria prior to
      the ancestor of all known eukaryotes.

PMID- 15980958
TI  - Considerations on the paper "Morphological convergence in Hippidion and Equus
      (Amerhippus) South American equids elucidated by ancient DNA analysis'', by
      Ludovic Orlando, Vera Eisenmann, Frederic Reynier, Paul Sondaar, Catherine Hanni.

PMID- 15980960
TI  - Decacotyle cairae n. sp. (Monogenea: Monocotylidae) from the gills of Pastinachus
      sp. (Elasmobranchii: Dasyatidae) from the South China Sea off Sarawak, Borneo,
      Malaysia.
AB  - Decacotyle cairae n. sp. (Monogenea: Monocotylidae) is described from the gills
      of an unidentified species of Pastinachus collected in the South China Sea off
      Sematan and Mukah, Sarawak, Borneo, Malaysia. D. cairae can be distinguished from
      the other six members of the genus by the presence of two simple unsclerotised
      accessory structures on the dorsal surface of the haptor in combination with a
      long, narrow, looping male copulatory organ. The host specimens of Pastinachus
      collected in Borneo also appear to be a new species and the monogenean data
      support this conclusion. A key to species of Decacotyle is given and their host
      specificity is discussed.

PMID- 15980959
TI  - Novel repetitive structures, deviant protein-encoding sequences and unidentified
      ORFs in the mitochondrial genome of the brachiopod Lingula anatina.
AB  - Complete sequence determination of the brachiopod Lingula anatina mtDNA (28,818
      bp) revealed an organization that is remarkably atypical for an animal mt-genome.
      In addition to the usual set of 37 animal mitochondrial genes, which make up only
      57% (16,555 bp) of the entire sequence, the genome contains lengthy unassigned
      sequences. All the genes are encoded in the same DNA strand, generally in a
      compact way, whereas the overall gene order is highly divergent in comparison
      with known animal mtDNA. Individual genes are generally longer and deviate
      considerably in sequence from their homologues in other animals. The genome
      contains two major repeat regions, in which 11 units of unassigned sequences and
      six genes (atp8, trnM, trnQ, trnV, and part of cox2 and nad2) are found in
      repetition, in the form of nested direct repeats of unparalleled complexity. One
      of the repeat regions contains unassigned repeat units dispersed among several
      unique sequences, novel repetitive structure for animal mtDNAs. Each of those
      unique sequences contains an open reading frame for a polypeptide between 80 and
      357 amino acids long, potentially encoding a functional molecule, but none of
      them has been identified with known proteins. In both repeat regions, tRNA genes
      or tRNA gene-like sequences flank major repeated units, supporting the view that
      those structures play a role in the mitochondrial gene rearrangements. Although
      the intricate repeated organization of this genome can be explained by recurrent
      tandem duplications and subsequent deletions mediated by replication errors,
      other mechanisms, such as nonhomologous recombinations, appear to explain certain
      structures more easily.

PMID- 15980961
TI  - Redescription of Amblyomma fuscum Neumann, 1907 (Acari: Ixodidae), a rare South
      America tick confirmed in Brazil.
AB  - The species Amblyomma fuscum Neumann, 1907 is a rare tick found on the
      Neotropical Region, but it has not been recorded as a valid taxon in some lists
      proposed by current taxonomists. After a comparison between the Brazilian
      material of A. fuscum deposited in the Acari Collection of the Butantan
      Institute, Sao Paulo, Brazil, and the male type deposited in Leiden Museum of
      Natural History, The Netherlands, we confirm the taxonomic validity of A. fuscum
      and redescribe the adult specimens based on light and scanning electron
      microscope studies.

PMID- 15980962
TI  - Grammatorcynicola n. g. (Bucephalidae: Dolichoenterinae) from Grammatorcynus spp.
      (Scombridae) on the Great Barrier Reef, Australia.
AB  - A new trematode genus, Grammatorcynicola n. g. (Bucephalidae: Dolichoenterinae),
      and two new species, G. brayi n. sp. and G. nolani n. sp. from the intestines of
      the scombrids, Grammatorcynus bicarinatus and Gr. bilineatus respectively, are
      reported from the Great Barrier Reef, Australia. Grammatorcynicola n. g. is
      placed in the Dolichoenterinae, as the pharynx is in the anterior quarter of the
      body, the caecum is tube-like and extends to the posterior quarter of the body,
      the cirrus-sac is small relative to the size of the worm when compared with other
      bucephalids and the pars prostatica is curved. Grammatorcynicola n. g. differs
      from other dolichoenterine genera in having a simple sucker-like rhynchus, the
      ovary anterior to the testes and by not having a particularly thick cirrus-sac
      wall.

PMID- 15980963
TI  - Sanguinicola maritimus n. sp. (Digenea: Sanguinicolidae) from Labridae
      (Teleostei: Perciformes) of southern Australian waters.
AB  - A new species of Sanguinicola Plehn, 1905 is described from the marine teleosts
      Notolabrus parilus (Richardson) and N. tetricus (Richardson) (Perciformes:
      Labridae) from Western Australian and Tasmanian waters. This host distribution is
      strikingly anomalous; however, the present material fulfils the morphological
      criteria of Sanguinicola. S. maritimus n. sp. differs from previously described
      species in having the combination of a body 1,432--1,701 mum long, the oesophagus
      18.3--21.7% of the body length, the testis occupying 42.8--52.3% of the body
      length, an oviducal seminal receptacle and Mehlis' gland present, ovoid eggs, and
      vitelline follicles that extend anteriorly past the nerve commissure, laterally
      past the lateral nerve chords and posteriorly to the anterior margin of the
      cirrus-sac. S. maritimus also lacks a protrusible anterior proboscis. It also
      differs in the combination of host and geographical location, being the first
      Sanguinicola species from a marine teleost and the first from Australian waters.

PMID- 15980964
TI  - Hungactinomyxon, a new actinosporean type and collective group(Myxozoa) from
      Branchiura sowerbyi Beddard (Oligochaeta).
AB  - Actinosporeans are characterised by great morphological diversity. As it has been
      proved that the class Actinosporea is a synonym of the Myxosporea, actinosporean
      genera have only been regarded only as actinosporean collective groups. While
      most actinosporeans are released individually by their oligochaete hosts, members
      of the synactinomyxon, siedleckiella and antonactinomyxon collective groups are
      released as eight connected structural elements. These actinosporean types are
      differentiated by the type of unit and junction of the caudal processes. On the
      basis of these characteristics, a new actinosporean type, constructed from eight
      echinactinomyxon units, is described as hungactinomyxon. Adjacent units are
      joined by two of their three processes and form two interconnected cubes, each
      containing four echinactinomyxons. Molecular biological studies also suggest that
      this new actinosporean type differs from other actinosporean types built up from
      eight structural elements for which 18S rDNA sequences are available in GenBank.

PMID- 15980965
TI  - Morphological and molecular comparison of Myxobolus procerus (Kudo, 1934) and M.
      intramusculi n. sp. (Myxozoa) parasitising muscles of the trout-perch Percopsis
      omiscomaycus.
AB  - Inter- and intracellular cysts from a presumed single species, Myxobolus procerus
      (Kudo, 1934), parasitising the trout-perch Percopsis omiscomaycus were compared
      with respect to their spore morphology and small subunit 18S ribosomal DNA. The
      two cyst types have similar pyriform spores and comparable ranges in spore length
      and width, size of the polar capsules and number of filament coils. However,
      fixed spores of the intracellular cysts are significantly shorter (p<0.05) in
      mean length than those from intercellular cysts, giving them a broader
      appearance. Comparing 991 base pairs of 18S rDNA revealed a 20 bp difference
      between the two cyst types (97.9% similarity), 10 due to base substitutions and
      10 due to the presence or absence of a base. The described morphological
      differences and consistent 2.1% difference in the 18S rDNA reveal that the
      intracellular form is a separate species, which is described herein as Myxobolus
      intramusculi n. sp. M. intramusculi n. sp. and M. procerus may be sister species
      and it is suggested that the two species arose through sympatric speciation
      involving a switch in site specificity within a single host species.

PMID- 15980966
TI  - Taxonomic revision of the cestodes of the family Progynotaeniidae
      (Cyclophyllidea) parasitising stone curlews (Charadriiformes: Burhinidae).
AB  - The type series of Progynotaenia evaginata Fuhrmann, 1909 from Burhinus
      senegalensis in Sudan, P. foetida Meggitt, 1928 from B. oedicnemus in Egypt and
      Angularia australis Maplestone, 1921 from B. grallarius in Australia are
      redescribed. As a comparative material, specimens of P. evaginata from B.
      oedicnemus in Kazakhstan were studied. The type-series of P. evaginata and P.
      foetida were found to be heterogeneous due to the presence of scoleces and
      fragments of cestodes of the genus Stenovaria Spasskii & Borgarenko, 1973
      (Dilepididae). For P. foetida, a lectotype is designated. P. foetida is
      recognised as a synonym of P. evaginata (new synonymy). Angularia australis,
      previously considered a member of the Dilepididae, is transferred to the
      Progynotaeniidae as a synonym of P. evaginata (new synonymy). The synonymy of P.
      indica Johri, 1963 with P. evaginata, proposed by Ryzhikov & Tolkacheva (1981),
      is supported. The host range and the geographical distribution of P. evaginata
      are restricted to birds of the genus Burhinus from the Eastern Hemisphere.

PMID- 15980967
TI  - Corynosoma australe Johnston, 1937 and C. cetaceum Johnston & Best, 1942
      (Acanthocephala: Polymorphidae) from marine mammals and fishes in Argentinian
      waters: allozyme markers and taxonomic status.
AB  - Genetic and morphological studies were carried out on acanthocephalans belonging
      to Corynosoma Luhe, 1904 and referable to the species C. cetaceum Johnston &
      Best, 1942 and C. australe Johnston, 1937, which were recovered from both
      definitive and intermediate hosts in Argentinian waters. The aims were to
      estimate the level of genetic differentiation between the two taxa at any stage
      of their life-cycle, to provide genetic (allozyme) markers for their recognition
      and to analyse the systematic status of both taxa. Acanthocephalans were
      collected from the stomach and intestine of Arctocephalus australis (Zimmerman),
      the intestine of Mirounga leonina (Linnaeus) and the stomach of Pontoporia
      blainvillei Gervais & D'Orbigny (definitive hosts) in Argentinian waters.
      Alternative alleles at all the 13 enzymatic loci studied were observed for C.
      australe and C. cetaceum. The specimens from the stomach of both P. blainvillei
      and A. australis were identified, on the basis of the great number of diagnostic
      loci found, as C. cetaceum; those from intestine of both A. australis and M.
      leonina as C. australe. A high level of genetic differentiation (D(Nei)=infinity:
      I(Nei)=0.00) between the two taxa was found, suggesting a generic distinction
      between the two species. Cystacanths of the two species from the body-cavity of
      the fish Cynoscion guatucupa (Cuvier) collected from the same geographical area
      were identified genetically. Morphological patterns, such as the number of hooks
      and hook rows on the proboscis, the distribution of somatic and genital armature,
      and other morphometric and meristic differences, in addition to ecological data,
      enabled the identification of these two species at cystacanth, juvenile and adult
      stages. However, a number of morphological and morphometric features of the
      Argentinian material were different to those of C. australe and C. cetaceum
      described from other regions of the world.

PMID- 15980968
TI  - Gene expression profile induced by BCNU in human glioma cell lines with
      differential MGMT expression.
AB  - Chemotherapy with the alkylating agent BCNU (1,3-bis (2-chloroethyl)-1
      nitrosourea) is the most commonly used chemotherapeutic agent for gliomas.
      However, the usefulness of this agent is limited because tumor cell resistance to
      BCNU is frequently found in clinical brain tumor therapy. The O6-methylguanine
      DNA methyltransferase protein (MGMT) reverses alkylation at the O6 position of
      guanine and we have reported the role of MGMT in the response of brain tumors to
      alkylating agents. However, the different mechanisms underlying the patterns
      related to MGMT remain unclear. To better understand the molecular mechanism by
      which BCNU exerts its effect in glioma cell lines according MGMT expression, we
      used microarray technology to interrogate 3800 known genes and determine the gene
      expression profiles altered by BCNU treatment. Our results showed that treatment
      with BCNU alters the expression of a diverse group of genes in a time-dependent
      manner. A subset of gene changes was found common in both glioma cell lines and
      other subset is specific of each cell line. After 24 h of BCNU treatment, up
      regulation of transcription factors involved in the nucleation of both RNA
      polymerase II and III transcription initiation complexes was reported.
      Interestingly, BCNU promoted the expression of actin-dependent regulators of
      chromatin. Similar effects were found with higher BCNU doses in MGMT+ cell line
      showing a similar mechanism that in MGMT-deficient cell with standard doses. Our
      data suggest that human glioma cell lines treated with BCNU, independently of
      MGMT expression, show changes in the expression of cell cycle and survival
      related genes interfering the transcription mechanisms and the chromatin
      regulation.

PMID- 15980969
TI  - Meningiomas expressing and responding to cholecystokinin (CCK).
AB  - The effect of cholecystokinin (CCK) on cultured human meningioma derived cells
      was investigated. Exposure of meningioma cells for 6-12 days to CCK-8s (2-200 nM)
      resulted in a dose dependent stimulation of cell growth to a maximum of 1.1-fold
      over basal controls. A time course study showed stimulation of cell growth at day
      3 followed by increase throughout day 6. The stimulatory effect of CCK on
      meningioma cell growth was completely abolished by a CCK-B specific receptor
      antagonist, L-365,260. Reverse-transcription of meningioma-derived RNA into cDNA
      followed by amplification by the polymerase chain reaction using specific primers
      for CCK peptide and its CCK-A and/B receptor revealed 100% presence of CCK
      peptide and CCK-B receptors mRNA whereas CCK-A receptor was expressed in 66% of
      the meningiomas. These results provide evidence that human meningioma cells
      possess CCK peptide and its receptors the activation of which leads to increase
      of cell growth possibly via an autocrine/paracrine mechanism.

PMID- 15980970
TI  - Beta-catenin mutations in craniopharyngiomas and pituitary adenomas.
AB  - Craniopharyngiomas and pituitary adenomas are both tumors of the hypothalamic and
      pituitary region, respectively that are frequently associated with endocrine
      defects either because of direct involvement of hormone producing cells (most
      pituitary tumors) or because of secondary defects due to disturbance of
      hypothalamic function (some pituitary tumors and craniopharyngiomas). Some
      studies suggest that mutant beta-catenin gene cells in craniopharyngiomas and
      pituitary adenomas contribute to their tumorigenesis. DNA was extracted from 73
      cranial tumors and subjected to polymerase chain reaction (PCR) with previously
      described primers encompassing glycogen synthase kinase-3beta phosphorylation
      sites of the beta-catenin gene. Sequenced PCR products for possible beta-catenin
      gene mutations showed a total of 7/43 alterations in adamantinomatous
      craniopharyngioma-derived DNA samples. Two previously described beta-catenin
      mutations in codon 33 TCT(Ser) > TGT(Cys) and codon 37 TCT(Ser) > TTT(Phe),
      whereas three novel mutations in codon 41 ACC(Thr) > ATC(Ile), codon 33 TCT(Ser)
      > TAT(Tyr) and codon 32 GAC(Asp) > AAC(Asn) were observed. None of the 22
      pituitary adenomas and the eight papillary craniopharyngiomas analyzed presented
      any sequence alterations. These findings demonstrate an association between beta
      catenin gene alterations and craniopharyngiomas of the adamantinomatous type.
      Since this gene product is involved with development, these results suggest that
      beta-catenin mutations may contribute to the initiation and subsequent growth of
      congenital craniopharyngiomas.

PMID- 15980971
TI  - Tumoral micro-blood vessels and vascular microenvironment in human astrocytic
      tumors. A transmission electron microscopy study.
AB  - The development of peritumoral edema is thought to be due to extravasation of
      plasma water and macromolecules through a defective blood-brain barrier (BBB),
      but the exact mechanism by which occurs is poorly understood. The aim of this
      study was analyze at submicroscopic level the morphological changes in both micro
      blood vessels and vascular microenvironment of astrocytic tumors in an attempt of
      understanding the pathological aspects that may help in the future researches for
      the design of future therapeutic strategies. Biopsies of 25 patients with
      pathological diagnosis of astrocytic tumors were examined with the transmission
      electron microscope. Both open and close tight junctions were observed in the
      micro-blood vessels, inclusive in a same tumor. Cytoskeletal disorganization
      associated with disintegrated perijunctional actin filaments were seen. The
      paracellular space showed enlargement and commonly occupied by fluid
      proteinaceous, endothelial cells display oncotic and ischemic changes, basal
      lamina reveals enlargement, edema, vacuolization and collagen fibers disposed in
      irregular array. Pericytes exhibited edema and phagocytoced material, astrocytic
      perivascular-feet showed signs of oncosis and necrosis, co-option vessels totally
      surrounding by neoplastic cells also were seen. The ultrastructural abnormalities
      observed in both junctional complexes and vascular microenvironment suggest a
      multi-factorial pathobiology process, probably hypoxia intratumoral, calcium
      overload in endothelial cells, and degradative effects of metalloproteinases over
      the basal membrane appear as determinant factors that leading to structural
      modifications of junctional complexes, therefore, treatment with both HIF-1alpha
      and metalloproteinases inhibitors possibly can contribute with the
      pharmacological handling of the peritumoral edema associated with astrocytic
      tumors.

PMID- 15980972
TI  - High throughput screening of meningioma biomarkers using a tissue microarray.
AB  - Meningiomas are histologically and clinically diverse CNS neoplasms with few
      available immunohistochemical markers of differentiation and progression.
      Therefore, we investigated a panel of potentially useful meningioma-associated
      biomarkers using high throughput tissue microarray immunohistochemistry (TMA-IHC)
      with a TMA that includes 9 hemangiopericytomas (HPCs) and 41 meningiomas spanning
      all grades, as well as two subsets of atypical meningiomas, stratified according
      to clinical behavior. Antibodies utilized were progesterone receptor (PR),
      epithelial membrane antigen (EMA), cathepsin D, E-cadherin, platelet derived
      growth factor (PDGF) receptor beta, PDGF BB ligand, survivin, epithelial growth
      factor receptor (EGFR), and vascular endothelial growth factor (VEGF). In most
      cases, frequencies of tumor positivity were similar to those previously reported
      using whole section IHC. EMA, E-cadherin, and PDGFR-beta staining patterns
      distinguished the anaplastic meningiomas from the HPCs (P < 0.001, P = 0.02, P =
      0.015, respectively). As in prior studies, PR and cathepsin D expression were
      inversely proportional to tumor grade. However, PR and EGFR were also
      differentially expressed between symptomatic, surgically resected benign
      meningiomas and incidental meningiomas found at autopsy. We conclude that (1) TMA
      IHC is an accurate and efficient way to rapidly assess biomarkers in meningeal
      tumors, (2) EMA, E-cadherin, and PDGFR-beta are useful in distinguishing
      anaplastic meningiomas from HPCs, and (3) the expression patterns for incidental
      meningiomas differ slightly from their surgically resected symptomatic
      counterparts.

PMID- 15980973
TI  - Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery
      to tumor--a pharmacokinetic study.
AB  - Solvent facilitated perfusion (SFP) has been proposed as a technique to increase
      the delivery of chemotherapeutic agents to tumors. SFP entails direct injection
      of the agent into the tumor in a water-miscible organic solvent, and because the
      solvent moves easily through both aqueous solutions and cellular membranes it
      drives the penetration of the solubilized anticancer agent throughout the tumor.
      To test this hypothesis, we compared the pharmacokinetics (PK) of 14C-labeled 1,3
      bis-chlorethyl-1-nitrosourea (BCNU) in intra-cerebral 9L rat gliomas after
      intravenous (IV) infusion in 90% saline--10% ethanol or direct intratumoral (IT)
      injection of 14C-BCNU in 100% ethanol (DTI-015). Treatment with DTI-015 yielded a
      peak radioactive count (Cmax) for the 14C label that was 100-1000 fold higher in
      the tumor than in all other tissues in addition to a concentration in the tumor
      that was 100-fold higher than that achieved following IV infusion of 14C-BCNU.
      Pathologic and auto-radiographic analysis of tissue sections following IT
      injection of 14C-BCNU in ethanol into either tumor or normal rat brain revealed
      both an enhanced local volume of distribution and an increased concentration of
      BCNU delivered to tumor compared to non-tumor bearing brain. To investigate the
      mechanism behind the SFP of BCNU to the tumor both dynamic contrast and perfusion
      MRI were performed on 9L tumors before and after treatment and demonstrated a
      decrease in tumor perfusion following IT injection of DTI-015. Finally, initial
      PK of patient blood samples following administration of DTI-015 into relapsed
      high-grade glioma indicated a 20-fold decrease in systemic exposure to BCNU
      compared to IV infusion of BCNU providing further evidence for the enhanced
      therapeutic ratio observed for DTI-015.

PMID- 15980974
TI  - Glioma dissemination along the corticospinal tract.

PMID- 15980975
TI  - Primary malignant rhabdoid tumor of the central nervous system--a comprehensive
      review.
AB  - This paper presents the case of an eight-year-old girl who presented with
      headache and vomiting and was found to harbor a right fronto-temporo-parietal,
      partially cystic and centrally solid tumor that measured 11 x 8 x 7 cm. This
      vascular tumor was gross totally removed. The initial histopathologic diagnosis
      was hemangiopericytoma and the patient received a total dose of 5330 cGy of
      external cranial radiation. Twelve months later, the patient presented with left
      lower quadrant pain and limping and the spinal MR scans showed metastases at T4
      5, T7, T12-L1 and L3 levels. The voluminous lesion at T12-L1 was surgically
      removed. Histopathological examination of both specimens revealed that both
      tumors in fact were malignant rhabdoid tumor (MRT). The patient did not benefit
      from spinal surgery and died 4 months later. A review of the literature has shown
      that since Briner et al'. first report in 1985 [Pediatr Pathol 3: 117-118, 1985],
      100 MRT cases have been published. More than two-thirds of reviewed cases
      presented with local recurrence or subarachnoid spread after a mean period of 6.9
      months after diagnosis and died two months later. Infratentorial and pineal
      location and surgery limited to biopsy were poor prognostic indicators. Twenty
      two cases remained alive at a mean period of 24.5 months. The longest survival
      with an intracranial MRT was 65 months. Of those remaining alive, 15 had no
      evidence of disease (NED). Our case is the first MRT case immunopositive for HMB
      45 and has also shown that the MRT cells grow aggressive over time as
      demonstrated by a four-fold increase in MIB-1 labeling index.

PMID- 15980976
TI  - Molecular genetics alterations and tumor behavior of sporadic vestibular
      schwannoma from the People's Republic of China.
AB  - OBJECTIVES: To analyze the molecular genetic alteration of sporadic vestibular
      schwannomas from the People's Republic of China and to correlate these
      alterations with the tumor behaviors. METHODS: Four highly polymorphic
      microsatellite DNA markers were used to observe the frequency of loss of
      heterozygosity (LOH) in chromosome 22. The NF2 gene mutations were detected by
      Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and
      DNA sequencing. The schwannomin/merlin (S/M) expression was examined using anti
      NF2 (A-19) IgG under immunohistochemistry and western blot. The proliferative
      index (LI) of vestibular schwannoma was evaluated by proliferative cell nuclear
      antigen investigation. RESULTS: Sixteen vestibular schwannomas (44.4%) showed
      allele loss. We found 22 mutations in 36 schwannomas. The LI and the growth rate
      of schwannomas with LOH or mutation were significantly higher than those without
      LOH or mutation. All of these vestibular schwannomas showed no immunoreaction to
      anti-NF2(A-19) IgG by immunohistochemistry. By immunoblotting technique, reduced
      expression of S/M was found in 31 cases (86%). The growth index of schwannomas
      with severely reduced expression of S/M was significantly higher than those with
      moderately reduced or normal expression. CONCLUSION: The molecular genetic
      changes in sporadic vestibular schwannomas from Chinese patients were similar to
      the previous reports. We demonstrate the relationship between tumor behaviors and
      genetic alteration (including LOH and mutation of NF2 gene). We propose that
      inactivation of S/M, may be an important step in tumorigenesis of sporadic
      vestibular schwannoma.

PMID- 15980977
TI  - Temozolomide-induced partial response in a patient with primary diffuse
      leptomeningeal gliomatosis.
AB  - Herein we describe the case of a patient with primary diffuse leptomeningeal
      gliomatosis (PDLG). After surgery and ventriculoperitoneal shunt placement, due
      to poor general conditions, the patient was not eligible for radiotherapy. For
      this reason we decided to start a systemic chemotherapy treatment with
      Temozolomide (150 mg/m2 per day for 5 days every 4 weeks). After three cycles a
      partial response was achieved with a clear improvement of general conditions. In
      our knowledge, this is the first time that PDLG treatment with Temozolomide has
      been described.

PMID- 15980978
TI  - Paraganglioma in sella.
AB  - We report a very rare case of a paraganglioma arising from sellar and suprasellar
      region which has been treated with radiotherapy following multiple surgeries.

PMID- 15980979
TI  - An unusual complication of cancer treatment for acute lymphoblastic leukemia.
AB  - Childhood cancer is a leading cause of mortality in children less than 15 years
      of age, accounting for about 10.4 of total childhood deaths [Robinson LL: In:
      Pizzo PA, Polack DA (eds) Principles and Practice of Pediatric Oncology, 3rd edn.
      Lippincott--Raven, Philadelphia--NewYork, 1997, pp. 1-10.]. As more aggressive
      therapeutic regimens have been adopted and ostensibly cured patients are being
      followed for longer periods of time, it has become increasingly clear that the
      treatment of cancer can have significant late effects on the growing child, one
      of the more troublesome of which is the induction of secondary malignancy. We
      report an 11-year-old child who, as supported by both clinical course and
      neuroimaging studies, developed an unusual complication eight years after
      completing therapy for acute lymphoblastic leukemia, gliomatosis cerebri.

PMID- 15980980
TI  - Treatment of recurrent cerebellar hemangioblastoma with external radiotherapy in
      a patient with von Hippel-Lindau disease: a case report and review of the
      literature.
AB  - Von Hippel-Lindau Disease, a multisystem familial cancer syndrome, is inherited
      as an autosomal-dominant trait. Common manifestations of the disease are retinal,
      cerebellar and medullary hemangioblastomas; renal cysts and carcinomas;
      pancreatic cysts; pheochromocytoma; and papilllary cystadenoma of the epididym.
      We report the case of a 40-year-old man with type I von Hippel-Lindau disease
      treated with external radiotherapy for recurrent cerebellar hemangioblastoma.

PMID- 15980981
TI  - Hemangiopericytoma in pregnancy: a case report.

PMID- 15980982
TI  - Malignant lymphoma of the trigeminal region. Case illustration.

PMID- 15980985
TI  - Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib
      (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by
      the Hellenic Cooperative Oncology Group.
AB  - Paclitaxel (Taxol) and carboplatin are an effective combination regimen for
      treating advanced breast cancer. Gefitinib (IRESSA) is the first epidermal growth
      factor receptor tyrosine kinase inhibitor to be approved for cancer treatment.
      This multicenter phase II trial treated 68 patients with advanced breast cancer
      with paclitaxel (175 mg/m(2) over 3 h) and 3-weekly carboplatin (area under the
      curve of 6) for six cycles, and 250 mg/day gefitinib orally. Median age was 57
      (range 35-77) years, patients had performance status 0 (69.1%), 1 (27.9%) 2
      (2.9%), 82.4% of patients had visceral metastases and 63.2% had received adjuvant
      chemotherapy. Forty-eight (70.6%) patients completed six cycles of chemotherapy
      and 20 (29.4%) patients discontinued treatment (seven [10.3%] due to disease
      progression, seven [10.3%] due to toxicity, five [7.4%] withdrew consent and one
      [1.5%] died after the first cycle). Sixty-three (92.7%) patients were evaluable
      for response; nine (13.2%) had complete responses, 30 (44.1%) had partial
      responses, 21 (30.9%) had stable disease and three (4.4%) had disease
      progression. Grade 3/4 adverse events in > or =5% of patients except of alopecia,
      included neutropenia (17.7%), anemia (10.3%), diarrhea (7.4%), thrombocytopenia
      (5.9%) and peripheral neuropathy (5.9%). Of those tumor biopsies available for
      immunohistochemical analysis (n=60), 5.0% were positive and 35.0% negative for
      expression of all HER-family receptors. Comparable numbers of tumor biopsies were
      nuclear p27(kipl) positive and negative (39.7 and 42.7%, respectively), with the
      majority (72.1%) negative for cytoplasmic p27(kipl). The observed efficacy data
      in this study were similar to those reported for the combination of paclitaxel
      and carboplatin alone.

PMID- 15980986
TI  - Soyfood intake and breast cancer survival: a followup of the Shanghai Breast
      Cancer Study.
AB  - Soy and its constituents have been shown in many in vivo and in vitro studies and
      in some epidemiological studies to have anti-cancer effects. Some soy
      constituents, however, also stimulate cell proliferation, which has raised
      concerns in promoting soy intake among breast cancer survivors. To investigate
      whether soy intake may be associated with breast cancer survival, we evaluated
      data from a cohort of 1459 breast cancer patients who participated in the
      Shanghai Breast Cancer Study between 1996 and 1998. Usual soy food intake was
      assessed using a validated food frequency questionnaire at baseline. The median
      follow-up time for this cohort of women was 5.2 years. We found that soy intake
      prior to cancer diagnosis was unrelated to disease-free breast cancer survival
      (adjusted hazard ratio [HR]=0.99, 95% confidence interval [CI], 0.73-1.33 for the
      highest tertile compared to the lowest tertile). The association between soy
      protein intake and breast cancer survival did not differ according to ER/PR
      status, tumor stage, age at diagnosis, body mass index (BMI), waist to hip ratio
      (WHR), or menopausal status. Additionally, the soy-survival association did not
      appear to vary according to XbaI or PvuII polymorphisms in ER-alpha, or
      C(14206)T, G(25652)A, or A(50766)G polymorphisms in ER-beta. These data suggest
      that soyfoods do not have an adverse effect on breast cancer survival.

PMID- 15980987
TI  - Breast cancer predisposing alleles in Poland.
AB  - Mutant alleles of several genes in the DNA repair pathway have been found to
      predispose women to breast cancer. From a public health perspective, the
      importance of a given allele in a population is determined by the frequency of
      the allele and by the relative risk of breast cancer that it confers. In Poland
      founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an
      increased risk of breast cancer, but the relative contribution of each of these
      alleles to the overall breast cancer burden has not yet been determined. We
      screened 2012 unselected cases of breast cancer and 4000 population controls for
      7 different mutations in these genes. Overall, a mutation was found in 12% of the
      cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in
      approximately equal measure to the burden of breast cancer in Poland. A BRCA1
      mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was
      associated with a higher odds ratio for breast cancer (OR=15) than were either of
      the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In
      contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1)
      than for the missense mutation I157T (OR=1.4). This study suggests that cancer
      risks may be specific for particular alleles of a susceptibility gene and that
      these different risks should be taken into account by genetic counselors.

PMID- 15980988
TI  - The impact of a second breast cancer diagnosis on health related quality of life.
AB  - A growing of research documents the negative impact of recurrent breast cancer on
      quality of life (QOL), however few prospective investigations are available that
      compare QOL outcomes across different types of second cancer events (e.g.,
      local/regional recurrence (LR) versus distant/metastatic recurrence (DR) versus a
      new primary breast cancer (NP)). In addition, although participant attrition is a
      major issue in this group of cancer patients, the potential impact of attrition
      or response bias on QOL outcomes is not typically examined. To address these
      issues, we prospectively examined QOL data obtained from a sample of women
      (n=140) participating in the Women's Healthy Eating and Living (WHEL) Study who
      experienced a second cancer event (LR, DR or NP). Women in our study reported
      significant worsening in most areas of QOL, except for emotional wellbeing, from
      pre- to post-second cancer event. Although the patterns of change to QOL differed
      slightly within each category (LR versus DR versus NP), participants were more
      similar than different in their QOL ratings. However, the perceived health status
      of women with DR was significantly lower than women with LR or NP. We also
      identify important sources of response bias that should be considered when
      interpreting findings. Specifically, women diagnosed with DR (a) were more likely
      to decline to complete the post-recurrence QOL questionnaire (27% refusal rate
      versus 14% LR and 13% NP), and (b) had higher death rates (28% death rate versus
      4% LR and 6% NP) after agreeing to but before completing the post-second
      diagnosis QOL questionnaire.

PMID- 15980989
TI  - Breast self-examination practices among women from six ethnic groups and the
      influence of cancer worry.
AB  - Diverse samples of women (N = 1364) from Brooklyn, New York, were interviewed
      regarding their breast cancer screening practices. Of interest here is the
      relation between cancer worry and adherence to breast self-examination (BSE)
      guidelines among the six ethnic groups identified--European American, African
      American, Haitian, Dominican and English-speaking Caribbean women. There was a
      significant difference in cancer worry by ethnicity. Logistic regression analysis
      indicated that education, cancer worry, and perceived efficacy of BSE
      significantly predicted adherence. Furthermore, there were significant
      differences among women of African descent in BSE adherence and cancer worry.
      These differences reflect the emerging need for researchers to empirically and
      methodically investigate ethnic and cultural factors, as well as emotions and
      affect in preventive health behaviors.

PMID- 15980990
TI  - Long-term dysregulation of circadian and 17-beta estradiol-induced LH, prolactin
      and corticosterone secretion after dimethylbenz (a) anthracene administration in
      the Sprague-Dawley female rat.
AB  - A single intragastric administration of 7,12-dimethylbenz (a) anthracene (DMBA)
      has been shown, when given at 55-60 days of age, to induce mammary tumors in
      young cycling female Sprague-Dawley rats. The appearance of the tumors is
      preceded by a series of neuroendocrine disturbances of the hypothalamo-pituitary
      gonadal (HPG) axis, including attenuation of the preovulatory Luteinizing Hormone
      (LH) and Gonadotropin-Releasing Hormone (GnRH) release and amplification of the
      preovulatory 17beta-Estradiol (E(2)) surge. In this study, we examined the
      hypothesis that a single administration of DMBA could also, in the long range,
      induce disturbances of others neuroendocrine axis, like the Hypothalamic
      Pituitary-Adrenal (HPA) axis and/or the Lactotroph axis. Sprague-Dawley rats, 55
      60 days of age, received, on the day of Estrous of the Estrous cycle, a single
      administration of 15 mg of DMBA delivered by intragastric intubation. Then, they
      were ovariectomized 5 days later. One month later, (1) Two groups of animal were
      sacrificed by decapitation at 09:00 a.m. and 05:00 p.m. to record the circadian
      rhythm of plasma LH, Prolactin (PRL) and corticosterone, (2) Three other groups
      of animal were sacrificed by decapitation at three different times after a
      morning subcutaneous administration of 50 microg/kg of Estradiol Benzoate (EB),
      to induce a negative and positive feed-back of the secretion of LH. Then, plasma
      LH, PRL and corticosterone concentrations were measured. After DMBA
      administration, (1) the negative--but not the positive--LH feed-back was seen,
      (2) the PRL circadian rhythm was blunted and the corticosterone circadian rhythm
      was almost absent, (3) the increase in PRL or Corticosterone plasma concentration
      was significantly reduced. In conclusion, a single administration of DMBA
      provokes a long-term dysregulation of not only the HPG axis but also of the
      lactotroph and HPA axis. These dysregulations, along with the already evidenced
      long-term inhibition of DMBA upon Melatonin secretion from the pineal gland,
      might accelerate the promotion of mammary tumors induced by the mammary
      carcinogen.

PMID- 15980991
TI  - Extracorporeal high intensity focused ultrasound treatment for patients with
      breast cancer.
AB  - PURPOSE: To investigate the safety, efficacy and feasibility of using high
      intensity focused ultrasound (HIFU) as a non-invasive treatment for patients with
      breast cancer. PATIENTS AND METHODS: Twenty-two patients with breast cancer were
      enrolled into this non-randomized prospective trial. Disease TNM stage was
      classified as stage I in 4 patients, stage II(A) in 9 patients, stage II(B) in 8
      patients, and stage IV in 1 patient. Tumor size ranged from 2 to 4.8 cm in
      diameter (mean 3.4 cm). All patients received chemotherapy, radiation and
      tamoxifen, following HIFU for the primary lesions. Outcome measures included
      radiological and pathologic assessment of the treated tumor, cosmesis, and local
      recurrence. A cumulative survival rate is calculated by using the Kaplan-Meier
      method. RESULTS: No severe complications were encountered after HIFU. Post
      operative imaging demonstrated positive response and regression of all treated
      lesions. Follow-up biopsy revealed coagulation necrosis of target tumor and
      subsequent replacement by fibroblastic tissue. After a median follow-up of 54.8
      months, 1 patient died, 1 was lost to follow-up, and 20 were still alive. Two of
      22 patients developed local recurrence. Five-year disease-free survival and
      recurrence-free survival were 95% and 89%, respectively. Cosmetic result was
      judged as good to excellent in 94% of patients. CONCLUSIONS: HIFU treatment is
      safe, effective, and feasible for patients with breast cancer. But, large-scale,
      multiple-center clinical trials will be needed to determine the future role of
      this novel modality.

PMID- 15980992
TI  - Radiological and surgical placement of port devices: a 4-year institutional
      analysis of procedure performance, quality of life and cost in breast cancer
      patients.
AB  - PURPOSE: The present study is designed to evaluate and compare percutaneous
      radiologic arm port (R) and surgical subclavian port (S) devices in two
      homogeneous sets of breast cancer patients in terms of safety, efficacy, quality
      of life (QoL) and cost analysis. MATERIAL AND METHODS: This study involved a
      retrospective review of a prospective databank including 200 consecutive port
      device implantation attempted procedures performed over a 4-year period, in two
      similar groups of 100 breast cancer women who underwent either the surgical
      cephalic vein cutdown approach or the percutaneous basilic vein catheterization
      for intravenous adjuvant chemotherapy. Parameters analyzed included technical
      success, procedure duration, complications, QoL and cost evaluation for both
      techniques. RESULTS: The success rate for port implantation was higher for R than
      for S placement (96% versus 91%). Mean implant duration time was 5.6 and 7.6
      months for R and S, respectively. The overall complication rate was 10 and 16%
      for R and S, respectively. Mean implant duration time, without any complication
      or death, was 6.4 and 7.8 months for R and S, respectively. Six and seven percent
      for R and S, respectively, had to be removed prematurely. Both techniques
      exhibited very good QoL. Direct costs were respectively euro 230.8 and 219.1 for
      R and S, respectively. CONCLUSION: The significant advantages of R over S include
      higher success rate, higher cosmetic results despite a 15% relative overcost for
      R placement. Both are indicated for breast cancer chemotherapy treatment,
      nevertheless R placement is mandatory in anxious patients who fear surgery, in
      case of previous cervico-thoracic irradiation or upper extremity venous
      thrombosis, or in patients at risk of respiratory insufficiency.

PMID- 15980993
TI  - Predictive value of apoptosis, proliferation, HER-2, and topoisomerase IIalpha
      for anthracycline chemotherapy in locally advanced breast cancer.
AB  - PURPOSE: Laboratory evidence indicates that tumor growth depends on the balance
      between cell proliferation and cell death, and many anticancer agents may exert
      their therapeutic effect by decreasing proliferation and increasing apoptosis.
      Additionally, clinical observations indicate that overexpression of HER-2 or
      topoisomerase IIalpha (topo IIalpha) may be predictors of better response to
      anthracyclines in breast cancer. The objective of this study was to determine if
      proliferation (Ki-67), apoptosis (TUNEL), and expression of HER-2 and topo
      IIalpha are affected by anthracycline treatment, and if these molecular markers
      predict anthracycline responsiveness. EXPERIMENTAL DESIGN: Thirty-three women
      with primary breast tumors > or =3 cm received either doxorubicin (75 mg/m(2)) or
      epirubicin (120 mg/m(2)) for 4 cycles before surgery. Clinical response was
      evaluated after 4 cycles of treatment. Changes in molecular markers were assessed
      from core needle taken before treatment (D0), at 24-48 h (Dl) and on day 7 (D7)
      while on treatment, and from the surgical specimen excised on day 84 (D84) after
      the fourth cycle of chemotherapy. RESULTS: The overall response rate was 51% (17
      of 33 patients), with a 12% complete clinical response rate (4 of 33 patients).
      There were trends for tumors with higher apoptosis and topo IIalpha at baseline
      (D0) to be more responsive to anthracyclines, p = 0.1 and p = 0.08, respectively.
      Median apoptosis increased from D0 to Dl (p = 0.06) while median Ki-67 decreased
      (p = 0.07). Overall, expression of HER-2 remained stable throughout the
      chemotherapy administration. By Day 84, topo IIalpha had significantly decreased
      from baseline in responders, while it increased in non-responders, p = 0.03.
      CONCLUSIONS: In human primary breast cancer, anthracycline treatment causes an
      early increase in apoptosis and a decrease in proliferation. In this pilot study,
      higher apoptosis and topo IIalphaa levels in primary tumors were associated with
      greater responsiveness to anthracyclines, and topo IIalpha levels declined in
      responsive tumors.

PMID- 15980994
TI  - The S-phase fraction of the aneuploid cell subpopulation is the biologically
      relevant one in aneuploid breast cancers.
AB  - BACKGROUND: In the case of DNA-aneuploid tumors there are no clear guidelines as
      to which S-phase fraction is the more relevant one: that corresponding to either
      the diploid or the aneuploid population, or rather an average of both. MATERIALS
      AND METHODS: We studied 280 breast cancer specimens from previously untreated
      patients. Histologically, 231 were ductal infiltrating carcinomas, 30 lobular
      infiltrating carcinomas and 19 corresponded to other, less frequent varieties.
      Postsurgically, 164 cases (58.6%) were classified as T1, 87 (31.1%) as T2 and 7
      as T3. The remaining 22 cases were multifocal, diffuse tumors. Flow cytometry was
      performed on fresh tumor tissue, and immunohistochemistry for hormone receptors,
      Ki67, c-erb-B2 and p53 on paraffin-embedded material. RESULTS: In diploid tumors,
      a high S-phase (above the 75th percentile) correlated significantly with Ki67
      expression > or =20% (p<0.0001). In aneuploid tumors, however, this was only the
      case for the aneuploid fraction of tumor cells (p< 0.0001). A high S-phase of
      diploid tumors correlated directly and significantly with a high histologic grade
      (p=0.04), a high nuclear grade (p=0.01), tumor size (p=0.0008), and inversely
      with estrogen (p<0.0001) and progesterone (p<0.0001) receptor expression. In
      aneuploid tumors, the aneuploid tumor fraction showed a direct and significant
      correlation with a high histologic grade (p=0.005), a high nuclear grade
      (p=0.001), mutant p53 expression (p=0.0009), and inversely with estrogen
      (p<0.0001) and progesterone (p=0.0001) receptor expression. A high S-phase of the
      diploid cell fraction of aneuploid tumors, on the other hand, just showed an
      inverse correlation with high nuclear grade of the tumors (p=0.02), and none
      whatsoever with all other tested parameters.

PMID- 15980995
TI  - No adverse effects of adjuvant chemotherapy on hippocampal volume in Japanese
      breast cancer survivors.
AB  - We investigated the adverse effects of adjuvant chemotherapy on the hippocampus
      in Japanese breast cancer survivors with (n=44) and without (n=31) adjuvant
      chemotherapy. There were no significant differences in hippocampal volume
      (magnetic resonance imaging) or additionally in memory function (Wechsler Memory
      Scale-Revised) between the two groups.

PMID- 15980996
TI  - Evaluation of the CD107 cytotoxicity assay for the detection of cytolytic CD8+
      cells recognizing HER2/neu vaccine peptides.
AB  - The recently reported FACS-based CD107 assay has been used in human HIV and CMV
      antigen models as well as in the ex vivo analysis of tumor cytolytic T cells in a
      melanoma model by a single group. The purpose of our study was to validate this
      assay and to use it in previously untested viral and tumor antigen models.
      Specifically, we investigated the use of the novel CD107 cytotoxicity assay in
      the detection of influenza and HER2/neu tumor-specific cytolytic CD8+ T cells.
      CD8+ T cells from HLA-A2+ healthy donors were stimulated with autologous
      dendritic cells pulsed with FluM or the HER2/neu peptides, E75 or GP2. These CD8+
      T cells were then tested in cytotoxicity assays at varying effector:target (E:T)
      ratios against T2 targets. Cytotoxicity was measured by detection of CD107a and b
      on the surface of CD8+ T cells. An E:T of 1:5 was found to optimize the resulting
      percentage of CD8+CD107+ T cells. E75- and GP2-stimulated CD8+ T cells were then
      tested in cytotoxicity assays with MCF-7 (HER2/neu+HLA-A2+) and AU565
      (HER2/neu+HLA-A2-) tumor cells. Cytotoxicity was measured by both the CD107 assay
      and the (51)Cr release assay. Results of cytotoxicity were then correlated
      between these two assays. In representative experiments, the CD107 assay
      identified average specific increases for E75- and GP2-stimulated cells of 4.26
      and 3.57%, respectively. These results correlated favorably with cytotoxicity as
      measured by the traditional (51)Cr assay. These findings confirm preliminary
      reports of the CD107 assay and suggest its usefulness for monitoring cancer
      trials.

PMID- 15980997
TI  - Lamivudine therapy in HBsAg-carrying breast cancer patients undergoing
      chemotherapy: prophylactic or preemptive?

PMID- 15980998
TI  - A prospective randomized study comparing a cervical carbon fiber cage to the
      Smith-Robinson technique with allograft and plating: up to 24 months follow-up.
AB  - INTRODUCTION: Intervertebral carbon fiber cages may reduce graft collapse and
      promote bony fusion. Their safety and efficacy in the cervical spine have been
      investigated; however, no study has compared the outcomes of anterior cervical
      decompression and placement of a carbon fiber cage with placement of allograft
      and plate. METHODS: Forty consecutive patients who met inclusion criteria were
      enrolled and randomized to anterior cervical discectomy with carbon fiber cage
      alone (n=20) or with allograft with plating (n=20). Clinical and radiographic
      evaluations were performed at baseline and at 6 weeks, 3, 6, 12 and 24 months.
      Neck and arm pain as well as neck disability index (NDI) were assessed at every
      visit. The Short Form (SF)-36 was completed prior to operation and at 12-month
      intervals. Cervical radiographs were evaluated pre-op and at every follow-up for
      evidence of fusion and instability. RESULTS: No significant difference was found
      between the two randomized groups with respect to pre-operative age (mean 50
      years), sex, employment status, duration of pain or cervical levels affected. The
      mean follow-up period was 14 months (range, 6-26 months). The clinical pain and
      disability improvements were similar for both treatments. Post-operative donor
      site pain was only present in the cage group, but not of significant long-term
      disability. At up to 24 months, NDI scores were significantly improved in both
      groups when compared with baseline. At 12 and 24 months, all SF-36 questionnaire
      responses were also improved in both the treatment groups. However, there was no
      statistically significant difference in outcomes between the two groups at any
      time. The fusion rate was 100% in both groups by 12 and 24 months, without
      evidence of instability. There were no differences in complications between both
      groups. CONCLUSIONS: The outcomes after cervical decompression and placement of a
      carbon fiber cage appear to be similar to cervical decompression with allograft
      and plating by the Smith-Robinson technique.

PMID- 15980999
TI  - Growth factor expression in degenerated intervertebral disc tissue. An
      immunohistochemical analysis of transforming growth factor beta, fibroblast
      growth factor and platelet-derived growth factor.
AB  - Degenerated intervertebral disc has lost its normal architecture, and there are
      changes both in the nuclear and annular parts of the disc. Changes in cell shape,
      especially in the annulus fibrosus, have been reported. During degeneration the
      cells become more rounded, chondrocyte-like, whereas in the normal condition
      annular cells are more spindle shaped. These chondrocyte-like cells, often
      forming clusters, affect extracellular matrix turnover. In previous studies
      transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth
      factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in
      herniated intervertebral disc tissue. In the present study the same growth
      factors are analysed immunohistochemically in degenerated intervertebral disc
      tissue. Disc material was obtained from 16 discs operated for painful
      degenerative disc disease. Discs were classified according to the Dallas
      Discogram Description. Different disc regions were analysed in parallel. As
      normal control disc tissue material from eight organ donors was used. Polyclonal
      antibodies against different growth factors and TGFbeta receptor type II were
      used, and the immunoreaction was detected by the avidin biotin complex method.
      All studied degenerated discs showed immunoreactivity for TGFbeta receptor type
      II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2,
      respectively, and none showed immunoreaction for PDGF. Immunopositivity was
      located in blood vessels and in disc cells. In the nucleus pulposus the
      immunoreaction was located almost exclusively in chondrocyte-like disc cells,
      whereas in the annular region this reaction was either in chondrocyte-like disc
      cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like
      disc cells were especially prevalent in the posterior disrupted area. In the
      anterior area of the annulus fibrosus the distribution was more even between
      these two cell types. bFGF was expressed in the anterior annulus fibrosus more
      often in chondrocyte-like disc cells than in fibroblast-like disc cells. Control
      discs showed cellular immunopositivity for only TGFbeta-1 and -2 and TGFbeta
      receptor type II . We suggest that growth factors create a cascade in
      intervertebral disc tissue, where they act and participate in cellular
      remodelling from the normal resting stage via disc degeneration to disc
      herniation.

PMID- 15981000
TI  - Cervical cyst of the ligamentum flavum and C7-T1 subluxation: case report.
AB  - A patient with progressive gait disturbance resulting from a cyst of the cervical
      ligamentum flavum associated with C7-T1 listhesis is reported. Surgical removal
      of the cyst improved the patient's myelopathy. Intraspinal degenerative cysts are
      preferentially located in the lumbar region:unusual is the cervical localization.
      Differential diagnosis includes ligamentum flavum cyst, synovial and ganglion
      cysts. Association between degenerative intraspinal cysts and listhesis is
      discussed. To our knowledge, this is the first case of cyst of the ligamentum
      flavum associated with cervical subluxation.

PMID- 15981001
TI  - Insight into the self-association of key enzymes from pathogenic species.
AB  - Self-association of protein monomers to higher-order oligomers plays an important
      role in a plethora of biological phenomena. The classical biophysical technique
      of analytical ultracentrifugation is a key method used to measure protein
      oligomerisation. Recent advances in sedimentation data analysis have enabled the
      effects of diffusion to be deconvoluted from sample heterogeneity, permitting the
      direct identification of oligomeric species in self-associating systems. Two such
      systems are described and reviewed in this study. First, we examine the enzyme
      dihydrodipicolinate synthase (DHDPS), which crystallises as a tetramer. Wild-type
      DHDPS plays a critical role in lysine biosynthesis in microbes and is therefore
      an important antibiotic target. To confirm the state of association of DHDPS in
      solution, we employed sedimentation velocity and sedimentation equilibrium
      studies in an analytical ultracentrifuge to show that DHDPS exists in a slow
      dimer-tetramer equilibrium with a dissociation constant of 76 nM. Second, we
      review works describing the hexamerisation of GDP-mannose pyrophosphorylase (GDP
      MP), an enzyme that plays a critical role in mannose metabolism in Leishmania
      species. Although the structure of the GDP-MP hexamer has not yet been
      determined, we describe a three-dimensional model of the hexamer based largely on
      homology with the uridyltransferase enzyme, Glmu. GDP-MP is a novel drug target
      for the treatment of leishmaniasis, a devastating parasitic disease that infects
      more than 12 million people worldwide. Given that both GDP-MP and DHDPS are only
      active in their oligomeric states, we propose that inhibition of the self
      association of critical enzymes in disease is an emerging paradigm for
      therapeutic intervention.

PMID- 15981002
TI  - Meningioma growth and interferon beta-1b treated multiple sclerosis: coincidence
      or relationship?
AB  - Although the coincidence of multiple sclerosis (MS) and central nervous system
      (CNS) tumors has been reported in over 30 cases in English literature, meningioma
      growth was associated with interferon-beta (INF-b) treated MS only in two of
      them. We report the case of a 19-year-old woman with clinically possible,
      laboratory supported MS, and a concomitant right intraventricular tumor with
      magnetic resonance imaging (MRI) characteristics consistent with meningioma
      (similar signal with grey matter on T1 and T2-weighted images and homogenous,
      intense enhancement). Two years after initiation of INF-b treatment, follow-up
      brain MRI revealed enlargement of the intraventricular mass and relative increase
      in the number of white matter lesions without significant clinical deterioration.
      She underwent almost total resection of the mass and histology confirmed the
      diagnosis of papillary meningioma. Based on the immunohistochemistry results, we
      speculate that INF-b resulted in meningioma growth by enhancing platelet derived
      growth factor (PDGF) receptors or/and down-regulating transforming growth factor
      receptors on the tumor itself.

PMID- 15981003
TI  - Immersion autometallographic tracing of zinc ions in Alzheimer beta-amyloid
      plaques.
AB  - An easy to perform autometallographic technique (AMG) for capturing zinc ions in
      Alzheimer plaques is presented. The possibility of visualizing loosely bound or
      free zinc ions in tissue by immersion autometallography (iZnS(AMG)) is a
      relatively recent development. The iZnS(AMG) staining is caused by zinc-sulphur
      nanocrystals created in 1-2 mm thick brain slices that are immersed in a 0.1%
      sodium sulphide, 3% glutaraldehyde phosphate buffered solution, the NeoTimm
      Solution (NTS), for 3 days. When the zinc-sulphur nanocrystals are subsequently
      silver-enhanced by autometallography, the plaques are readily identified as
      spheres of dark interlacing strands of different sizes, embedded in the pattern
      of zinc-enriched terminals. The zinc specificity of the iZnS(AMG) technique was
      tested by immersion of brain slides in the chelator DEDTC prior to the NTS
      immersion. The iZnS(AMG) detection of zinc ions is easily standardized and can be
      used in the quantification of plaques with stereological methods. This technique
      is the first to detect zinc in plaques in the cerebellum of transgenic PS1/APP
      mice and the first to detect zinc ions in plaques and dystrophic neurites at
      electron microscopical levels.

PMID- 15981004
TI  - Genomics of plant cell wall biogenesis.

PMID- 15981005
TI  - Mixed-ligand complexes of ruthenium(II) containing new photoactive or
      electroactive ligands: synthesis, spectral characterization and DNA interactions.
AB  - Mixed-ligand ruthenium(II) complexes of three photoactive ligands, viz., (E)-1-[2
      (4-methyl-2-pyridyl)-4-pyridyl]-2-(1-naphthyl)-1-ethene (mppne), (E)-1-(9
      anthryl)-2-[2-(4-methyl-2-pyridyl)-4-pyridyl]-1-ethene (mppae) and (E)-1-[2-(4
      methyl-2-pyridyl)-4-pyridyl]-2-(1-pyrenyl)-1-ethene (mpppe), in which a 2,2'
      bipyridyl unit is linked via an ethylinic linkage to either a naphthalene, an
      anthracene or a pyrene chromophore and three electroactive ligands, viz., 4-(4
      pyridyl)-1,2-benzenediol (catpy), 5,6-dihydroxy-1,10-phenanthroline (catphen) and
      1,2-benzenediol (cat), were synthesized in good to moderate yields. Complexes
      [Ru(bpy)(2)(mppne)](2+) (bpy is 2, 2'-bipyridyl), [Ru(bpy)(2)(mppae)](2+),
      [Ru(bpy)(2)(mpppe)](2+), [Ru(bpy)(2)(sq-py)](+), [Ru(bpy)(2)(sq-phen)](+) and
      [Ru(phen)(2)(bsq)](+) (phen is 1,10-phenanthroline) were fully characterized by
      elemental analysis, IR, (1)H NMR, fast-atom bombardment or electron-impact mass,
      UV-vis and cyclic voltammetric methods. In the latter three complexes, the
      ligands catpy, catphen and cat are actually bound to the metal center as the
      corresponding semiquinone species, viz., 4-(4-pyridyl)-1,2-benzenedioleto(+I) (sq
      py), 1,10-phenanthroline-5,6-dioleto(+I) (sq-phen) and 1,2-benzenedioleto(+I)
      (bsq), thus making the overall charge of the complexes formally equal to + 1 in
      each case. These three complexes are electron paramagnetic resonance active and
      exhibit an intense absorption band between 941 and 958 nm owing to metal-to
      ligand charge transfer (MLCT, d (Ru)-->pi*(sq)) transitions. The other three
      ruthenium(II) complexes containing three photoactive ligands, mppne, mppae and
      mpppe, exhibit MLCT (d (Ru)-->pi*(bpy) ) bands in the 454-461-nm region and are
      diamagnetic. These can be characterized by the (1)H NMR method.
      [Ru(bpy)(2)(mppne)](2+), [Ru(bpy)(2)(mppae)](2+) and [Ru(bpy)(2)(mpppe)](2+)
      exhibit redox waves corresponding to the Ru(III)/Ru(II) couple along with the
      expected ligand (bpy and substituted bpy) based ones in their cyclic and
      differential pulse voltammograms (CH(3)CN, 0.1 M tetrabutylammonium
      hexafluorophosphate)-corresponding voltammograms of [Ru(bpy)(2)(sq-py)](+),
      [Ru(bpy)(2)(sq-phen)](+) and [Ru(phen)(2)(bsq)](+) are mainly characterized by
      waves corresponding to the quinone/semiquinone (q/sq) and semiquinone/1,2-diol
      (sq/cat) redox processes. The results of absorption and fluorescence titration as
      well as thermal denaturation studies reveal that [Ru(bpy)(2)(mppne)](2+) and
      [Ru(bpy)(2)(mppae)](2+) are moderate-to-strong binders of calf thymus DNA with
      binding constants ranging from 10(5) to 10(6) M(-1). Under the identical
      conditions of drug and light dose, the DNA (supercoiled pBR 322) photocleavage
      activities of these two complexes follow the
      order:[Ru(bpy)(2)(mppne)](2+)>[Ru(bpy)(2)(mppae)](2+), although the emission
      quantum yields follow the reverse order. The other ruthenium(II) complexes
      containing the semiquinone-based ligands are found to be nonluminescent and
      inefficient photocleavage agents of DNA. However, experiments shows that
      [Ru(bpy)(2)(sq)](+)-based complexes oxidize the sugar unit and could be used as
      mild oxidants for the sugar moiety of DNA. Possible explanations for these
      observations are presented.

PMID- 15981006
TI  - Factors modulating the pH at which calcium and magnesium phosphates precipitate
      from human urine.
AB  - The factors controlling the rate at which crystalline bacterial biofilms develop
      on indwelling bladder catheters are poorly understood. It is known that normally
      the pH of voided urine (pHv) is lower than the pH at which calcium and magnesium
      phosphates come out of urine solution (pHn). In patients who develop infections
      with urease producing bacteria, however, the pHv rises above the pHn and
      precipitation of the phosphates occurs in the urine and the biofilm. The aim of
      this study was to examine ways of manipulating the pHn of urine so that more of
      its calcium and magnesium remain in solution under alkaline conditions. The
      experimental data show that pHn can be elevated by decreasing the calcium,
      magnesium and phosphate concentrations. Increasing the fluid intake of a human
      subject so that the urinary calcium fell from 120 mg/l to 25 mg/l, for example,
      resulted in the pHn increasing from 6.48 to 8.22. The addition of citrate to
      urine also produced a rise in the pHn. The daily consumption of 500 ml of fresh
      orange juice increased urinary citrate concentrations from 0.35 to around 1.21
      mg/ml and the pHn rose from 7.24 to 8.2. The pHn of urine is thus a highly
      variable parameter. It can be manipulated by controlling the urinary
      concentrations of magnesium, calcium, phosphate and citrate ions. We suggest that
      increasing fluid intake with citrate containing drinks would reduce the extent of
      encrustation on catheters in patients infected with urease producing bacteria.

PMID- 15981007
TI  - Redox-iodometry: a new potentiometric method.
AB  - A new iodometric method for quantifying aqueous solutions of iodide-oxidizing and
      iodine-reducing substances, as well as plain iodine/iodide solutions, is
      presented. It is based on the redox potential of said solutions after reaction
      with iodide (or iodine) of known initial concentration. Calibration of the system
      and calculations of unknown concentrations was performed on the basis of
      developed algorithms and simple GWBASIC-programs. The method is distinguished by
      a short analysis time (2-3 min) and a simple instrumentation consisting of pH/mV
      meter, platinum and reference electrodes. In general the feasible concentration
      range encompasses 0.1 to 10(-6) mol/L, although it goes down to 10(-8) mol/L
      (0.001 mg Cl2/L) for oxidants like active chlorine compounds. The calculated
      imprecision and inaccuracy of the method were found to be 0.4-0.9% and 0.3-0.8%,
      respectively, resulting in a total error of 0.5-1.2%. Based on the experiments,
      average imprecisions of 1.0-1.5% at c(Ox)>10(-5) M, 1.5-3% at 10(-5) to 10(-7) M,
      and 4-7% at <10(-7) M were found. Redox-iodometry is a simple, precise, and time
      saving substitute for the more laborious and expensive iodometric titration
      method, which, like other well-established colorimetric procedures, is clearly
      outbalanced at low concentrations; this underlines the practical importance of
      redox-iodometry.

PMID- 15981009
TI  - The crescent sign: dissociation of the polyethylene liner from a modular
      acetabular component in total hip arthroplasty.
AB  - OBJECTIVE: To study whether there was a common pattern of clinical symptoms,
      signs and radiographic features for the dissociation of the polyethylene liner
      from an acetabular component and to postulate reasons for these features. DESIGN
      AND PATIENTS: Retrospective study of notes and radiographs of cases of revision
      hip arthroplasty for polyethylene liner dissociation of the cementless Harris
      Galante I porous-coated acetabular component (Zimmer Inc, Warsaw, IN) at the Avon
      Orthopaedic Centre, Bristol, UK and St. Mary's Hospital, Bristol, UK between 1995
      and 2004. Patients were contacted to confirm preoperative symptoms. RESULTS: Nine
      cases of late polyethylene liner dissociation of this prosthesis have been
      revised in these institutions. All patients presented with a reduction in
      mobility, groin pain and limp. Eight patients reported an audible noise on hip
      movement. In all cases, radiographs showed radiolucency medial to the femoral
      neck in association with an eccentrically placed femoral head showing contact
      with the acetabular metal shell, which we have termed the "crescent sign."
      CONCLUSIONS: There is a typical clinical presentation in this study. The
      diagnosis can be made from a single anteroposterior pelvic radiograph without the
      need for previous films for comparison, or the need for arthrography. Clinicians
      should look specifically for the crescent sign when an eccentrically placed
      femoral head has been noted, in order to differentiate the more unusual diagnosis
      of dissociation from that of polyethylene wear. Early revision surgery can
      prevent damage to the femoral head and metal acetabular shell, thus reducing the
      complexity of revision surgery.

PMID- 15981008
TI  - Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in
      bedridden medical in-patients: a prospective randomised double-blind study.
AB  - BACKGROUND: Hospitalised medical patients are at significant risk of venous
      thromboembolic disease through fatal pulmonary embolism; low-molecular-weight
      heparins have been proved efficient in preventing deep venous thrombosis in
      surgical and medical patients, but their effect on mortality in bedridden medical
      patients remains unknown. METHODS: In a multi-centre, randomised, double-blind,
      placebo-controlled study, 2,474 consecutive patients aged over 40 years admitted
      to internal medicine departments in the last 24 h and unable to move alone were
      randomised to receive 0.3 ml nadroparin (7,500 anti-Xa units) or placebo for up
      to 21 days. The primary end-point was overall mortality at day 21. RESULTS: There
      were no significant differences between the patients' characteristics. Overall
      mortality between the two groups was not statistically different [10.08% (124 of
      1,230) versus 10.29% (128 of 1,244), respectively, in the nadroparin and in the
      placebo groups; relative risk reduction 0.02, CI (-0.27, +0.25), P=0.89]. An
      autopsy was performed in 123 of the 252 patients who died (49%). Pulmonary
      embolism was discovered at autopsy in 10 of 63 patients in the nadroparin group
      and in 17 of 60 in the placebo group [relative risk reduction 0.38, CI (-0.27,
      +0.70), P=0.13]. CONCLUSION: Nadroparin does not have a significant effect on
      mortality in bedridden medical patients, based on the study results. The study
      provides no data suggesting that low-molecular-weight heparins might reduce the
      incidence of thromboembolic in-patients hospitalised for an acute medical
      disease.

PMID- 15981010
TI  - Linkage map construction in allotetraploid creeping bentgrass (Agrostis
      stolonifera L.).
AB  - Creeping bentgrass (Agrostis stolonifera L.) is one of the most adapted bentgrass
      species for use on golf course fairways and putting greens because of its high
      tolerance to low mowing height. It is a highly outcrossing allotetraploid species
      (2n=4x=28, A(2) and A(3) subgenomes). The first linkage map in this species is
      reported herein, and it was constructed based on a population derived from a
      cross between two heterozygous clones using 169 RAPD, 180 AFLP, and 39
      heterologous cereal and 36 homologous bentgrass cDNA RFLP markers. The linkage
      map consists of 424 mapped loci covering 1,110 cM in 14 linkage groups, of which
      seven pairs of homoeologous chromosomes were identified based on duplicated loci.
      The numbering of all seven linkage groups in the bentgrass map was assigned
      according to common markers mapped on syntenous chromosomes of ryegrass and
      wheat. The number of markers linked in coupling and repulsion phase was in a 1:1
      ratio, indicating disomic inheritance. This supports a strict allotetraploid
      inheritance in creeping bentgrass, as suggested by previous work based on
      chromosomal pairing and isozymes. This linkage map will assist in the tagging and
      eventually in marker-assisted breeding of economically important quantitative
      traits like disease resistance to dollar spot (Sclerotinia homoeocarpa F.T.
      Bennett) and brown patch (Rhizoctonia solani Kuhn).

PMID- 15981011
TI  - Learned modification of the nictitating membrane reflex by auditory stimuli in
      the barn owl.
AB  - The barn owl, Tyto alba, extends its nictitating membrane (NM) in response to an
      air puff to the cornea or a mild para-orbital electrodermal shock. The NM
      extension habituated rapidly if the stimulus was repeated. Habituation was
      prevented by pairing the aversive stimulus with a sound. The sound stimulus did
      not, by itself, induce an NM extension. Repeated pairing of sound with the
      aversive stimulus caused the subjects to modify the duration of their NM
      extension, increasing the duration when exposed to longer aversive stimuli and
      decreasing in response to shorter stimuli. No transference of the response was
      seen from the aversive stimulus to the sound. The learned change in duration of
      the NM extension resisted extinction. This modification of the NM extension
      reflex resembles previous descriptions of primer-produced facilitation.

PMID- 15981012
TI  - Pharmacological properties of neuronal TTX-resistant sodium channels and the role
      of a critical serine pore residue.
AB  - Voltage-gated sodium channels can be characterized by their sensitivity to
      inhibitors. Na(v)1.5 is sensitive to block by cadmium and extracellular QX-314,
      but relatively insensitive to tetrodotoxin and saxitoxin. Na(v)1.4 is
      tetrodotoxin- and saxitoxin-sensitive but resistant to cadmium and extracellular
      QX-314. Na(v)1.8 and Na(v)1.9 generate slowly inactivating (I(TTXr-Slow)) and
      persistent (I(TTXr-Per)) currents in sensory neurons that are tetrodotoxin
      resistant. Tetrodotoxin sensitivity is largely determined by the identity of a
      single residue; tyrosine 401 in Na(v)1.4, cysteine 374 in Na(v)1.5 and serine 356
      and 355 in Na(v)1.8 and Na(v)1.9. We asked whether Na(v)1.8 and Na(v)1.9 share
      other pharmacological properties as a result of this serine residue. I(TTXr-Slow)
      and I(TTXr-Per) were saxitoxin-resistant and resistant to internal QX-314. I(TTXr
      Slow) was also resistant to external QX-314 and displayed a approximately
      fourfold higher sensitivity than I(TTXr-Per) to cadmium. The impact of the serine
      residue was investigated by replacing tyrosine 401 in Na(v)1.4 with serine
      (Y401S) or cysteine (Y401C). Both mutants were resistant to tetrodotoxin and
      saxitoxin. Whereas Na(v)1.4-Y401C displayed an increased sensitivity to cadmium
      and extracellular QX-314, the serine substitution did not alter the sensitivity
      of Na(v)1.4 to cadmium or QX-314. Our data indicates that while the serine
      residue determines the sensitivity of I(TTXr-Slow) and I(TTXr-Per) to
      tetrodotoxin and saxitoxin, it does not determine their insensitivity to QX-314
      or their differential sensitivities to cadmium.

PMID- 15981013
TI  - Alzheimer pathology associated with POLG1 mutation, multiple mtDNA deletions, and
      APOE4/4: premature ageing or just coincidence?

PMID- 15981014
TI  - Abundant neuritic inclusions and microvacuolar changes in a case of diffuse Lewy
      body disease with the A53T mutation in the alpha-synuclein gene.
AB  - We report here a case of diffuse Lewy body disease with the A53T mutation in the
      alpha-synuclein gene. The proband presented at the age of 41 years with
      parkinsonism that was poorly responsive to levodopa. She subsequently developed
      cognitive impairment and moderate dementia, and died at the age of 50. Her
      father, paternal grandfather and uncle were all reported to have suffered from
      Parkinson's disease. Staining of tissue sections from the proband's brain with
      hematoxylin-eosin and alpha-synuclein antibodies showed small numbers of Lewy
      bodies in a few brain regions. This contrasted with large numbers of Lewy
      neurites and neuroaxonal spheroids in many brain regions. By electron microscopy,
      Lewy neurites consisted of abnormal filaments and dense granular material.
      Isolated filaments resembled those previously described in idiopathic Parkinson's
      disease and dementia with Lewy bodies. They were decorated by antibodies specific
      for the N and C termini of alpha-synuclein, indicating the presence of the full
      length protein. Nucleus accumbens and the lower layers in limbic areas of the
      cerebral cortex showed prominent vacuolation, with frequent clustering of
      microvacuoles around Lewy neurites. Nerve cell loss was most extensive in dorsal
      motor nucleus of the vagus nerve, substantia nigra and nucleus basalis of
      Meynert. Neurofibrillary tangles and senile plaques were not observed. However,
      in several brain regions, a few widely scattered tau-positive nerve cell bodies
      and neurites were present. By electron microscopy, Alzheimer-type paired helical
      and straight filaments were seen.

PMID- 15981015
TI  - Rhabdoid cystic papillary meningioma with diffuse subarachnoid dissemination.

PMID- 15981016
TI  - Unusual features of mitochondrial degeneration in skeletal muscle of patients
      with nuclear complex I mutation.

PMID- 15981017
TI  - Perceptual evaluation of substitution voices: development and evaluation of the
      (I)INFVo rating scale.
AB  - Substitution voicing cannot be evaluated accurately by the GRBAS perceptual
      rating scale, and there is a need for a valuable alternative. Therefore, we
      developed and tried out a perceptual rating scale, consisting of five new
      parameters: impression, intelligibility, noise, fluency and voicing, each to be
      scored between 0 (very bad score) to 10 (very good score for a substitution
      voice). In analogy to the GRBAS scale, they are then converted to deviance scores
      ranging from 0 (similar to good substitution voicing) to 3 (very deviant from
      good substitution voicing). Inter-individual agreement measured in a set of 24
      semi-professional jury members seemed to be moderate for all parameters. Mean
      figures of 0.52, 0.51, 0.46, 0.53 and 0.46 are obtained for the parameters
      impression, intelligibility, noise, fluency and voicing, respectively. Because a
      high correlation exists between the first two parameters (0.917) and relying on
      the correlation figures between the two "I"s and the other parameters
      (correlation values for "impression" vary from 0.79-0.86; values for
      "intelligibility" range from 0.74-0.83), we suggest to discard the parameter
      impression, which turns the actual IINFVo scale into INFVo. The proposed (I)INFVo
      perceptual rating scale seems promising for the assessment of substitution
      voicing. Eventual improvements and practical proposals are discussed.

PMID- 15981018
TI  - Jaw stretch reflexes in children.
AB  - The substantial morphological transformations that occur during human development
      present the nervous system with a considerable challenge in terms of motor
      control. Variability of skilled motor performance is a hallmark of a developing
      system. In adults, the jaw stretch reflex contributes to the functional stability
      of the jaw. We have investigated the response properties of the jaw stretch
      reflex in two groups of young children and a group of young adults. Response
      latencies increased with development, and all age groups produced stimulus
      magnitude-dependent increases in reflex gain and resulting biting force. Reflex
      gain was largest for the older children (9-10 years), yet net increases in
      resulting biting force were comparable across age groups. These data and earlier
      experiments suggest that oral sensorimotor pathways mature throughout childhood
      in concert with the continued acquisition of complex motor skills.

PMID- 15981020
TI  - Diagnosis of osteoporosis: visual assessment on conventional versus digital
      radiographs.
AB  - In many radiological departments conventional radiography has been replaced by
      digital radiography. Therefore, the purpose of this study was to analyze the
      visual detection of osteopenia/osteoporosis with both digital and conventional
      radiographs. In 286 patients we retrospectively evaluated radiographs of the
      lumbar spine in two planes. One hundred twenty-eight patients had conventional
      and 158 patients had digital radiographs. Patients with pre-existing vertebral
      fractures were excluded. Four experienced musculoskeletal radiologists blinded to
      the values of DXA and to the patients' ages assessed independently from each
      other whether the bone density of the lumbar spines was normal or decreased. The
      results of dual X-ray absorptiometry served as the standard of reference. The
      threshold value for the diagnosis of osteopenia was a T-score less than -1 SD
      according to the WHO classification of osteoporosis. Sensitivity/specificity was
      86%/36% for conventional and 72%/47% for digital radiographs. The overall
      diagnostic accuracy was 68% for conventional and 64% for digital radiographs.
      Eighty percent of the patients with osteopenia and 96% of the patients with
      osteoporosis were correctly assessed as true positive on conventional radiographs
      and 65% (osteopenia) and 82% (osteoporosis) on digital radiographs. Interobserver
      agreement was markedly lower for digital (35%) than for conventional radiographs
      (73%). However, the differences were not statistically significant. There is no
      major difference in diagnostic accuracy in the assessment of
      osteopenia/osteoporosis using digital and conventional radiographs, respectively.
      However, the high interobserver variance on digital radiographs indicates that
      visual assessment of osteoporosis/osteopenia is problematic, which may be due to
      image processing and postprocessing algorithms that manipulate the visual aspect
      of bone density.

PMID- 15981019
TI  - Economic evaluations of interventions for the prevention and treatment of
      osteoporosis: a structured review of the literature.
AB  - Economic evaluations are increasingly being used by decision-makers to estimate
      the cost-effectiveness of interventions. The objective of this study was to
      conduct a structured review of economic evaluations of interventions to prevent
      and treat osteoporosis. Articles were identified independently by two reviewers
      through searches on MEDLINE, the bibliographies of reviews and identified
      economic models, and expert opinion, using predefined inclusion and exclusion
      criteria. Data on country, type and level of interventions, type of fractures,
      interventions, study population and the authors' stated conclusions were
      extracted. Forty-two relevant studies were identified. The majority of studies
      (71%) were conducted in Sweden, the UK and the US. The main interventions
      investigated were hormone replacement therapy (27%), bisphosphonates (17%) and
      combinations of vitamin D and calcium (16%). In 38% of studies, hip fracture was
      the sole fracture outcome. Eighty-eight percent (88%) of studies investigated
      female populations only. A relatively large number of economic evaluations were
      identified in the field of osteoporosis. Major changes have recently occurred in
      the treatment of this disease, following the publication of the results of the
      Women's Health Initiative trial. Methodological developments in economic
      evaluations, such as the use of probabilistic sensitivity analysis and cost
      effectiveness acceptability curves, have also taken place. Such changes are
      reflected in the studies that were reviewed. The development of economic models
      should be an iterative process that incorporates new information, whether
      clinical or methodological, as it becomes available.

PMID- 15981021
TI  - Rationale, objectives and design of the Direct Analysis of Nonvertebral Fracture
      in the Community Experience (DANCE) study.
AB  - The experience in randomized placebo-controlled clinical trials may differ from
      that in community practice. The pivotal teriparatide [rhPTH(1-34)] studies were
      initiated when few therapeutic options for osteoporosis were available. The
      Direct Analysis of Non-Vertebral Fractures in Community Experience (DANCE) study
      is a prospective observational trial designed to examine the occurrence of
      nonvertebral fragility fractures in a large, diverse patient population treated
      with teriparatide. The occurrence of clinical vertebral fractures and back pain
      will also be examined, as will bone mineral density, bone mineral content, bone
      area, safety and tolerability. Subjects will be followed through a course of
      teriparatide therapy for up to 24 months and for an additional 24 months after
      cessation of treatment. Therefore, subjects may participate in this study for up
      to 48 months. DANCE will provide data on the effectiveness and tolerability of
      teriparatide therapy in clinical practice that will complement the results of
      published controlled clinical trials.

PMID- 15981022
TI  - Distinct effects of PPARgamma insufficiency on bone marrow cells, osteoblasts,
      and osteoclastic cells.

PMID- 15981023
TI  - Gene expression of connective tissue growth factor (CTGF/CCN2) in calcifying
      tissues of normal and cbfa1-null mutant mice in late stage of embryonic
      development.
AB  - Connective tissue growth factor (CTGF/CCN2), one of the most recently described
      growth factors, is produced by chondrocytes, vascular endothelial cells, and
      transforming growth factor (TGF)-beta-stimulated fibroblasts. CTGF was isolated
      from a chondrosarcoma-derived chondrocytic cell line, HCS-2/8, and found to be
      normally expressed in cartilage tissues, especially in hypertrophic chondrocytes,
      and also to stimulate both the proliferation and the differentiation of
      chondrocytes in vitro. Therefore, CTGF is thought to be one of the most important
      regulators of endochondral ossification in vivo. Herein we describe the
      expression pattern of the ctgf gene in the calcifying tissues of normal
      developing mouse embryos in comparison with that in core binding factor a1
      (Cbfa1)-targeted mutant (cbfa1-null) mouse embryos, in which impaired development
      and growth were characteristically observed in the skeletal system. After 15 days
      of development (E15), the expression of ctgf was detected in the zone of
      hypertrophy and provisional calcification, in which ossification proceeds toward
      the epiphysis during the skeletal development of the mouse embryo. Furthermore,
      ctgf was expressed in developing molar and incisal tooth germs around the
      perinatal stage. However, no expression of the gene was found in the cbfa1-null
      mouse embryos. These results indicate that CTGF may have certain important roles
      in the development of the calcifying tissues in the mouse embryo.

PMID- 15981024
TI  - How many days per week should rats undergo running exercise to increase BMD?
AB  - The aim of the present study was to examine the effect of different frequencies
      of running exercise on increasing bone mineral density (BMD) and improving bone
      histomorphology at various sites of the skeleton (tibia, femur, and second lumbar
      vertebra) in young rats. Twenty-five female Wistar rats, 8 weeks old, were
      divided into five groups, of 5 animals each according to running load: control
      group, no running (A group); running load (RL), 4 days per week (d/w; B group);
      RL, 5 d/w (C group); RL, 6 d/w (D group); and RL, 7 d/w (E group). Rats ran on a
      treadmill at a speed of 15 m/min for 30 min per day over an 8-week period. The
      results indicated that the BMD of the tibia in the B, C, D, and E groups and that
      of the femur in the B and E groups increased significantly over that of the A
      group. However, the cortical BMD and trabecular BMD of the second lumbar vertebra
      did not change. In regard to bone histomorphometry of the tibia, a parameter of
      bone resorption (eroded surface/bone surface) was significantly lower in the B
      and D groups than in the A group. There were no differences in the parameters of
      bone formation. Tartaric acid-resistant acid phosphatase (TRACP) values were
      significantly lower in the B and C groups than in the A group. There were
      significant increases in body weight in the B group and in muscle weight in the C
      group. From the data obtained in this study, it was concluded that increases in
      BMD were obtained by a moderate running load at frequencies of 4 and 5 days per
      week.

PMID- 15981025
TI  - Incadronate disodium inhibits joint destruction and periarticular bone loss only
      in the early phase of rat adjuvant-induced arthritis.
AB  - Destruction of articular cartilage and subchondral bone loss in the affected
      joints of rat adjuvant arthritis have never been quantified histologically. This
      study aimed to evaluate the effect of incadronate disodium on joint destruction
      and periarticular bone loss, using histomorphometric measurements. Seven-week-old
      female Lewis rats were injected with 0.1 mg of heat-killed Mycobacterium
      butyricum into the tail base. Immediately after sensitization, vehicle, or
      incadronate at 10 or 100 microg/kg per day, was administered subcutaneously,
      three times per week. Hind-paw volume was measured weekly and the animals were
      killed at 2, 4, 6, and 10 weeks after sensitization. After taking X-rays,
      decalcified sagittal sections of the ankle joint were prepared and stained with
      toluidine blue and tartarate-resistant acid phosphatase. Articular cartilage
      destruction and subchondral bone loss were evaluated histomorphometrically. At 2
      weeks after sensitization, no radiographic or histologic changes were observed.
      However, at 4 weeks, severe articular cartilage destruction and subchondral bone
      loss were found in the arthritic control group, while these changes were
      inhibited dose-dependently by incadronate treatment. At 6 and 10 weeks, both the
      destructive changes and the bone loss had further progressed, and they were not
      inhibited by incadronate treatment. Incadronate dose-dependently inhibited
      articular cartilage destruction and subchondral bone loss at 4 weeks after
      sensitization in this adjuvant arthritis model. However, the suppressive effects
      of incadronate did not continue until 6 and 10 weeks.

PMID- 15981026
TI  - Osteogenic potentials with joint-loading modality.
AB  - Osteogenic potentials with a novel joint-loading modality were examined, using
      mouse ulnae as a model system. Load-induced deformation of rigid bone is known to
      generate interstitial fluid flow and stimulate osteogenesis. However, in most of
      the previous studies, loads were applied to cortical bone. In the current study,
      we addressed the question of whether deformation of the epiphysis underneath the
      joint would enhance bone formation in the epiphysis and the diaphysis. In order
      to answer the question, we applied lateral loads to a mouse elbow and conducted a
      bone histomorphometric analysis, as well as measurements of strains and streaming
      potentials. Compared to the no-loading control, the histomorphometric results
      showed that 0.5-N loads, applied to the elbow at 2 Hz for 3 min/day for 3
      consecutive days, increased the mineralizing surface (two- to threefold), the
      rate of mineral apposition (three- to fivefold), and the rate of bone formation
      (six- to eightfold) in the ulna. Strain measurements indicated that strains of
      around 30 microstrain, induced with the joint-loading modality, were under the
      minimum effective strain of around 1000 microstrain, which is considered
      necessary to achieve strain-driven bone formation. To evaluate the induction of
      fluid flow with the joint-loading modality, streaming potentials were measured in
      separate experiments, using mouse femurs ex vivo. We found that the streaming
      potentials correlated to the magnitude of the load applied to the epiphysis (r(2)
      = 0.92), as well as the flow speed in the medullary cavity (r(2) = 0.93). Taken
      together, the findings of the current study support the idea of joint-loading
      driven osteogenesis, through a mechanism that involves the induction of fluid
      flow in cortical bone.

PMID- 15981027
TI  - Vitamin D deficiency and reduced bone mineral density in multiple sclerosis:
      effect of ambulatory status and functional capacity.
AB  - Multiple sclerosis (MS) is a chronic disease and a major cause of disability in
      young adults. The aims of this study were to assess bone mass in patients with MS
      in comparison to healthy age- and sex-matched controls, and to evaluate factors
      influencing bone mineral density (BMD), and the relationship of the pain
      threshold at peripheral and axial sites with BMD in MS. Thirty-one patients with
      MS and 30 matched healthy controls participated in the study. The Kurtzke
      expanded disability status scale (EDSS) and the functional independence measure
      (FIM) were used to scale disability, mobility, and functional status. Serum
      25(OH) vitamin D levels were measured. BMD was measured using dual X-ray
      absorptiometry (DXA). MS patients had significantly lower BMD at the lumbar spine
      (L2-L4) and femur trochanter compared to the matched controls. BMD of the lumbar
      spine was nearly 1 SD lower in MS patients compared with the healthy reference
      population (Z scores). MS patients had significantly lower vitamin D levels (17.3
      ng/ml vs 43.1 ng/ml; P < 0.001) compared to controls, and 19 patients (61%) had a
      serum level of vitamin D that was less than 20 ng/ml. EDSS scores in the patients
      were inversely correlated with proximal femur BMD but not with spinal BMD. There
      was a negative correlation with the cumulative steroid dose and BMD only for
      femur trochanter BMD. Total myalgia scores for paravertebral muscles correlated
      significantly with spinal BMD. In conclusion, BMD is significantly lower in MS
      patients than in healthy controls, vitamin D deficiency is prevalent in MS, and
      ambulatory status is a determinative factor for osteoporosis in MS. Patients
      should be encouraged to have adequate sunlight exposure and to increase their
      mobility. Specific strengthening exercises for hip and back muscles in MS
      patients would have a substantial impact on bone density, osteoporosis, fracture
      risk, and mobility.

PMID- 15981028
TI  - Relationship between bone mineral density and urine level of NTx in rheumatoid
      arthritis.
AB  - We analyzed the relationship between the level of type-I collagen N-telopeptide
      (NTx) in urine (U-NTx) and bone mineral density (BMD) in patients with rheumatoid
      arthritis (RA). The subjects were 62 female patients with RA who had experienced
      the menopause 5 years or more before the study commenced, and who had not been
      treated for osteoporosis. The mean age of the subjects was 61.6 years and the
      mean disease duration was 13.3 years. They were classified for global functional
      status (classes I to IV), and then grouped based on the presence or absence of
      corticosteroid administration. Bone mineral density (BMD) and U-NTx levels were
      measured. In the presence of corticosteroid administration (CS group; n = 40),
      the mean level of U-NTx/creatinine (Cr) was 88.8 nM and the percent young adult
      mean (%YAM) for BMD was 71.2%. In the no corticosteroid (nCS group; n = 22), the
      values were 72.1 nM and 78.2%, respectively. The U-NTx/Cr value and %YAM were not
      significantly different between the CS group and the nCS group. A negative
      correlation was observed between the U-NTx/Cr value and %YAM in both groups (P =
      0.005 and P = 0.0265). No significant difference was observed for the U-NTx/Cr
      value or %YAM between the CS and nCS groups, in any class. In the CS group, a
      positive correlation was observed between the U-NTx/Cr value and the total dose
      of corticosteroid (P = 0.001), and a negative correlation was observed between
      the %YAM and the total dose of corticosteroid (P = 0.003). These results
      suggested that preventive medical treatment for osteoporosis is required for RA
      patients in class III, irrespective of whether they have had corticosteroid
      administration.

PMID- 15981029
TI  - Nail calcium and magnesium content in relation to age and bone mineral density.
AB  - In view of the importance of calcium (Ca) and magnesium (Mg) as major bone
      components and nutrients controlling bone metabolism, and the ready availability
      of nail samples for analysis, clippings of fingernails and toenails were analyzed
      for Ca and Mg. The clippings were dissolved in nitric acid and analysis was done,
      using atomic absorption spectrophotometry, in 169 women and 115 men between 20
      and 80 years of age. Fingernail Ca concentration in men decreased from 927 +/- 50
      ppm (mean +/- SEM) in their twenties to 464 +/- 50 ppm in their eighties, with a
      significant negative correlation with age (r = -0.322; P < 0.0001) and such a
      negative correlation was also shown in the women (r = -0.269; P = 0.0004).
      Toenail Ca concentrations also decreased significantly with age in men (r = 
      0.534; P < 0.0001) and women (r = -0.224; P = 0.0016). Fingernail Mg
      concentration, in contrast, increased significantly with age in both men (r =
      0.209; P = 0.0145) and women (r = 0.280; P < 0.0001), but toenail Mg failed to
      show significant changes with age in either men or women. Multiple stepwise
      regression analysis of age and lumbar bone mineral density (LBMD) on fingernail
      Ca concentration eliminated age before LBMD. In a separate group of 33 women in
      their sixties, a significant positive correlation was noted between fingernail Ca
      and LBMD (r = 0.544; P = 0.0016) and between toenail Ca and LBMD (r = 0.399; P =
      0.0215). A negative correlation was also noted between fingernail Mg
      concentration and LBMD (r = -0.389; P = 0.0252). Nail mineral content may be
      utilized as one of the indicators of bone mineral metabolism.

PMID- 15981030
TI  - Association and linkage analyses of interleukin-6 gene 634C/G polymorphism and
      bone phenotypes in Chinese.
AB  - In this study, we tested the interleukin-6 (IL-6) gene as an important candidate
      gene for its linkage and association with the variation of bone phenotypes (bone
      mineral density [BMD] and bone size) in young Chinese female subjects. We
      genotyped the IL-6 gene at the -634C/G restriction fragment length polymorphism
      (RFLP) site (ID, RS1800796) in 1263 individuals from 402 Chinese nuclear
      families, composed of both parents and at least one healthy daughter (mean age +/
      SD, 31.4 +/- 5.8 years). Using the daughters' bone phenotypes, we tested total
      family association, within-family association (via transmission disequilibrium
      test, [TDT]), and linkage, between the -634C/G marker and bone phenotypes at the
      spine and the hip. No significant association or linkage was found for bone size
      and BMD, although a trend was observed for linkage between the IL-6 gene -634C/G
      marker and L1-4 spinal BMD (adjusted for age, weight, and height). Our results,
      together with the findings from other studies, indicate that the IL-6 gene,
      although important for postmenopausal bone loss, may have a limited impact on
      peak bone mass variation in a Chinese population.

PMID- 15981031
TI  - Heterotopic ossification in bilateral knee and hip joints after long-term
      sedation.

PMID- 15981032
TI  - Low dose of oral alendronate decreases bone turnover in Japanese patients with
      Paget's disease of bone.

PMID- 15981033
TI  - Effects of N-acetylcysteine on lead-exposed PC-12 cells.
AB  - The neurotoxicity of lead has been well established through numerous studies.
      However, the cellular processes of lead neurotoxicity, as well as techniques to
      prevent or reverse cellular damage after lead exposure, remain unknown. If
      oxidative stress plays a primary role in lead-induced neurotoxicity, antioxidants
      should assist in reviving lead-exposed cells. The present study explores N
      acetylcysteine (NAC) as an antioxidant agent in PC-12 cells after lead exposure.
      Selective oxidative stress parameters, including glutathione (GSH), glutathione
      disulfide (GSSG), and malondialdehyde (MDA), were measured in PC-12 cells exposed
      to various concentrations of lead acetate. Administering NAC after lead exposure
      improved cell survival as measured by Trypan Blue exclusion. NAC treatment also
      increased the GSH/GSSG ratio compared to the lead-only group, and reduced MDA to
      near control levels. These results imply that NAC protects cells from lead
      induced oxidative damage by boosting the PC-12 cells' antioxidant defense
      mechanisms.

PMID- 15981035
TI  - Detoxification of cyanide by woody plants.
AB  - Vascular plants possess an enzyme system that detoxifies cyanide by converting it
      to the amino acid asparagine. This paper examines the potential of three woody
      plants from the Salicaceae family to degrade cyanide. Pre-rooted trees were grown
      in carefully designed bioreactors with aqueous solution spiked with potassium
      cyanide at 23.0 +/- 1 degree C for a maximum of 144 h. Cyanide concentrations
      ranged from 0.95 to 1.15 CN mg/L. Cyanide in water and in plant tissues was
      analyzed spectrophotometrically. Results from the investigation indicated that
      significant reduction of aqueous cyanide was found during the presence of plants
      in all treatments. Little amounts of applied cyanide were detected in the tissues
      of plants, mainly in roots and bottom stem. Cyanide remaining in tissues varied
      with the species of plants, despite similar periods of exposure. The data also
      indicated that photolysis, hydrolysis, and microbial degradation were not
      occurring and that volatilization was minimal. In conclusion, transport and
      metabolism of cyanide in plants is most likely.

PMID- 15981034
TI  - Concentrations of cadmium, lead, and zinc in fish from mining-influenced waters
      of northeastern Oklahoma: sampling of blood, carcass, and liver for aquatic
      biomonitoring.
AB  - The Tri-States Mining District (TSMD) of Missouri (MO), Kansas (KS), and Oklahoma
      (OK), USA, was mined for lead (Pb) and zinc (Zn) for more than a century. Mining
      ceased more than 30 years ago, but wastes remain widely distributed in the
      region, and there is evidence of surface- and groundwater contamination in the
      Spring River-Neosho River (SR-NR) system of northeastern OK. In October 2001, we
      collected a total of 74 fish from six locations in the SR-NR system that included
      common carp (Cyprinus carpio), channel- and flathead catfish (Ictalurus punctatus
      and Pylodictis olivaris), largemouth- and spotted bass (Micropterus salmoides and
      Micropterus punctulatus), and white crappie (Pomoxis annularis). We obtained
      additional fish from locations in MO that included three reference sites and one
      site that served as a "positive control" (heavily contaminated by Pb). Blood,
      carcass (headed, eviscerated, and scaled) and liver (carp only) samples were
      analyzed for cadmium (Cd), Pb, and Zn. Our objectives were to assess the degree
      to which fish from the OK portion of the SR-NR system are contaminated by these
      elements and to evaluate fish blood sampling for biomonitoring. Concentrations of
      Cd and Pb in carp and catfish from OK sites were elevated and Pb concentrations
      of some approached those of the highly contaminated site in MO, but
      concentrations in bass and crappie were relatively low. For Zn, correlations were
      weak among concentrations in the three tissues and none of the samples appeared
      to reflect site contamination. Variability was high for Cd in all three tissues
      of carp; differences between sites were statistically significant (p < 0.05) only
      for blood even though mean liver concentrations were at least 100-fold greater
      than those in blood. Blood concentrations of Cd and Pb were positively correlated
      (r2 = 0.49 to 0.84) with the concentration of the same element in carp and
      catfish carcasses or in carp livers, and the corresponding multiple regression
      models were highly significant (p < or = 0.001). Our data indicate that
      potentially nonlethal blood sampling can be useful for monitoring of selected
      metals in carp, catfish, and perhaps other fishes.

PMID- 15981036
TI  - Quantitative ultrastructure of metal-sequestering cells reflects intersite and
      interspecies differences in earthworm metal burdens.
AB  - Morphometric analysis of transmission electron micrographs was used to compare
      the effects of metals on the multifunctional, metal-sequestering, chloragocyte
      cells of two epigeic earthworm species, Dendrodrilus rubidus and Lumbricus
      rubellus, inhabiting three field soils: a clean circumneutral reference soil
      (Dinas Powys); an acidic moderately Pb- and Zn-contaminated soil (Cwmystwyth);
      and a calcareous Cd-, Pb-, and Zn-contaminated soil (Draethen). The main findings
      were: (1) D. rubidus accumulated significantly higher tissue Cd and Pb and lower
      Zn concentrations than L. rubellus, especially at Draethen; (2) the volume
      fraction of chloragosomes was significantly lower and the volume fraction of
      debris vesicles significantly higher in D. rubidus from Draethen compared with L.
      rubellus at all sites and with the other two D. rubidus populations; (3)
      estimated relative toxicity factors, derived from soil metal concentrations and
      published EC50 data, suggested that the subcellular changes in chloragocytes,
      particularly in D. rubidus from Draethen, were caused mainly by Zn and Pb
      exposures; (4) scrutiny of the body burdens of each metal in both worm species
      across the three sites indicated that Cd was a major contributor to the
      structural changes observed in Draethen D. rubidus, and its impact was
      disproportionate to its soil and tissue concentrations in comparison with those
      of Pb and Zn. The apparent greater susceptibility of D. rubidus cells, compared
      with L. rubellus cells, to soil metal contaminants is discussed in light of
      differences in the quality and quantity of the metal body burdens accumulated by
      the two species. Further histopathalogic and morphometric studies on key organs
      and tissue of earthworms are required to provide biomarkers of exposure and to
      underpin linkage of biochemical-level changes and demography.

PMID- 15981037
TI  - Time- and tissue-dependent polychlorinated biphenyl residues in hairless mice
      after exposure to polychlorinated biphenyl-contaminated soil.
AB  - Four groups of 16 age-matched female Crl:SKH1-hrBR hairless mice were exposed to
      either control soil or polychlorinated biphenyl (PCB)-contaminated soil
      (retrieved from an electrical waste landfill in Southern Illinois) for 11 weeks.
      The mice were exposed in a study to determine interactions between environmental
      PCBs and ultraviolet radiation (UVR), but the UVR group did not differ and
      provided a replicate for the residue study. Ear biopsies were performed
      immediately after the termination of soil exposure. The mice were maintained in
      regular bedding for 37 weeks thereafter. The ear-skin, trunk-skin, fat-pad, and
      liver samples were collected and weighed at the end of the study (week 48) and
      analyzed for PCB residues. A total of 141 PCB congeners were target analytes.
      There were significant differences in body weights and food consumption from week
      2 to 28. The liver weights of mice treated with PCB only were significantly
      greater than those of UVR-treated mice. The fat-pad weight did not differ among
      treated groups. PCB residues in the ear biopsies specimens of mice exposed to
      contaminated soil were 342.3 and 317.2 ppm in the PCB- and PCB + UVR-treated
      groups, respectively, and contained both persistent and episodic congeners. After
      37 weeks of isolation from soil, the ear PCB residues decreased to 21.5 ppm (PCB
      group) and 14.5 ppm (PCB + UVR group), and only persistent congeners contributed
      to the total PCB residues. The accumulation of PCB residues was highest in the
      fat pad (fat pad > ear skin > trunk skin > liver) in both PCB +/- UVR groups at
      the end of the study. However, the percentage of individual congeners
      contributing to total PCBs in these different tissues did not differ.

PMID- 15981038
TI  - Preventing and treating parastomal hernia.
AB  - Parastomal hernia represents a major surgical challenge. There is no uniform
      definition of parastomal hernia, and the true rate is therefore difficult to
      establish, although it is probably higher than 30%. Many surgical techniques have
      been tried to prevent and treat parastomal hernia; but despite these efforts,
      herniation continues to be a problem. The only method that has reduced the rate
      of parastomal hernia in a randomized trial is the use of a prophylactic
      prosthetic mesh. A large-pore low-weight mesh with reduced polypropylene content
      and a high proportion of absorbable material placed in a sublay position at the
      primary operation significantly reduces the rate of parastomal hernia. Recurrence
      rates after surgical treatment of parastomal hernia are high unless mesh is used.
      Relocation of the stoma, with prophylactic mesh in a sublay position at the new
      site and sublay mesh repairing the incisional hernia at the primary site, is the
      standard method for treating parastomal hernia in our department.

PMID- 15981039
TI  - Groin hernia repair: anesthesia.
AB  - The choice of anesthesia for groin hernia repair is between general, regional
      (epidural or spinal), and local anesthesia. Existing data from large consecutive
      patient series and randomized studies have shown local anesthesia to be the
      method of choice because it can be performed by the surgeon, does not necessarily
      require an attending anesthesiologist, translates into the shortest recovery
      (bypassing the postanesthesia care unit), has the lowest cost, and has the lowest
      postoperative morbidity regarding risk of urinary retention. Spinal anesthesia
      has no documented benefits for this small operation and should be avoided owing
      to the risk of rare neurologic side effects and the high risk of urinary
      retention. General anesthesia with short-acting agents may be a valid alternative
      when combined with local infiltration anesthesia, although an anesthesiologist is
      required. Despite sufficient scientific data to support the choice of anesthesia,
      large epidemiologic and nationwide information from databases show an undesirable
      high (about 10-20%) use of spinal anesthesia and low (about 10%) use of local
      infiltration anesthesia. Surgeons and anesthesiologists should therefore adjust
      their anesthesia practices to fit the available scientific evidence.

PMID- 15981040
TI  - Groin hernia repair: postherniorrhaphy pain.
AB  - Persistent pain after hernia repair is common, although it is usually mild. In 3%
      of patients it is severe, however, and has significant effects on work and social
      activities. The purpose of this review was to examine factors that affect pain
      after hernia repair. Although the type of anaesthetic used, local or general, and
      the operation type, open or laparoscopic, seems to affect acute pain, chronic
      persistent pain is influenced by the age of the patient and whether the hernia
      was painful preoperatively. Preliminary evidence indicating that use of a
      lightweight mesh may reduce chronic pain requires further research before
      definitive conclusions can be drawn.

PMID- 15981041
TI  - Ill-defined edge on ultrasonographic examination can be a marker of aggressive
      characteristic of papillary thyroid microcarcinoma.
AB  - We have previously demonstrated that, although most papillary thyroid
      microcarcinomas (PMC) do not grow or grow only slowly, cases showing lateral node
      metastasis diagnosed by ultrasonography (US) show an aggressive characteristic
      associated with poor disease-free survival. In this study, we focused on two
      prominent U.S. features: tumor, edge definition and strong echoes. We
      investigated whether these findings reflect aggressive characteristics of PMC in
      a series of 155 cases. Poor edge definition was observed in 21.5% of patients,
      all of who showed worse disease-free survival (p = 0.0477) than those with a well
      defined edge. Furthermore, this finding was directly linked to US-diagnosed
      lateral node metastasis (p = 0.0001). Strong echoes were observed in 63.9% of the
      cases, and fine strong echoes were seen in 25.2%. Cases demonstrating fine strong
      echoes tended to frequently show recurrence (p = 0.0902), and this finding was
      also significantly linked to US-diagnosed lateral node metastasis (p = 0.0494).
      These findings suggest that an ill-defined tumor edge is an important US feature
      of biologically aggressive PMC. We should carefully follow such patients,
      regardless of the therapeutic strategy, observation, or surgical treatment
      chosen.

PMID- 15981042
TI  - A critical comparison of robotic versus conventional laparoscopic splenectomies.
AB  - The benefit of robotic systems for general surgery is a matter of debate. We
      compare our initial series of robotic splenectomies with our first series of
      conventional laparoscopic ones. A retrospective analysis of the first six robotic
      versus the first six conventional laparoscopic splenectomies is presented.
      Patients were matched with regard to age, body-mass index, ASA score, and
      preoperative platelet levels. All procedures were performed by a single surgeon.
      Size and weight of the resected specimens were comparable in both groups. Median
      overall operating time was 154 (range, 115-292) min for the robotic and 127
      (range, 95-174) min for the laparoscopic group. No complications occurred. There
      were no open conversions. The median postoperative hospital stay was 7 (robotic
      group) and 6 (laparoscopic group) days. Median average costs were 6927 dollars
      for the robotic procedure versus $4084 for the conventional laparoscopic
      procedure (p < 0.05). Minimally invasive splenectomies are feasible using either
      conventional laparoscopic techniques or the da Vinci robotic system. In this
      analysis, procedures performed with the da Vinci robotic system resulted in
      prolonged overall operative time and significantly higher procedural costs. The
      use of a robotic system for laparoscopic splenectomy offers, at this stage, no
      relevant benefit and thus is not justified.

PMID- 15981043
TI  - Usefulness of an estimation of physiologic ability and surgical stress (E-PASS)
      scoring system to predict the incidence of postoperative complications in
      gastrointestinal surgery.
AB  - Surgical intervention induces various host responses to maintain homeostasis.
      When postoperative inflammation is intense and persists for a long time,
      postoperative complications may occur, sometimes developing into multiple organ
      failure. Therefore, it is very important to assess surgical stress and predict
      the risk of morbidity and mortality. Using a new scoring system, an estimation of
      physiologic ability and surgical stress (E-PASS) scoring system, surgical stress
      following gastrointestinal surgery was evaluated to assess the feasibility of
      this scoring system. This system comprises a preoperative risk score (PRS), a
      surgical stress score (SSS), and a comprehensive risk score (CRS) that is
      calculated from both the PRS and the SSS. The relationship of the E-PASS score to
      the incidence of morbidity and mortality was examined. The relationship between
      the E-PASS score and a sequential organ failure (SOFA) score was also evaluated.
      The CRS had a significant positive correlation between not only the incidence but
      also the grade of postoperative complications. Total maximum SOFA score in
      patients with a CRS of more than 1 was significantly higher than that in patients
      with a CRS of less than 1. In conclusion, the E-PASS scoring system will be
      useful for predicting and recognizing the risk of postoperative complications.
      This scoring system is brief, simple, and reproducible and can be useful in all
      types of hospitals.

PMID- 15981044
TI  - The impact of the risk factor "age" on the early postoperative results of surgery
      for colorectal carcinoma and its significance for perioperative management.
AB  - The risks and benefits of surgery for colorectal cancer in old patients have not
      been unequivocally defined. The present investigation was carried out in 309
      hospitals as a prospective multicenter study. In the period between 1 January
      2000 and 31 December 2001, a total of 19,080 patients were recruited for the
      study; 16,142 (84.6%) patients were younger than 80 years (<80) and 2932 (15.4%)
      were 80 years and older (> or =80). Significant differences between the age
      groups were observed for general postoperative complications (22.3% for <80
      years; 33.9% for > or =80). Specific postoperative complications were identical
      in both groups. Overall, significantly elevated morbidity and mortality rates
      were found with increasing age (morbidity: 33.9% vs. 43.5%; mortality: 2.6% vs.
      8.0%). The distribution of tumor stages revealed a significantly higher
      percentage of locally advanced tumors in the older age group (stage II: 28.0% vs.
      34.4%). In contrast, no increase in metastasizing tumors was found in the older
      age group (stage IV: 17.4% vs. 14.1%). Logistic regression showed that, in
      concert with a number of other parameters, age is a significant influencing
      factor on postoperative morbidity and mortality. The increase in postoperative
      morbidity and mortality rates associated with aging is a result of the increase
      in general postoperative complications, in particular, pneumonia and
      cardiovascular complications. Age as such does not represent a contraindication
      for surgical treatment. The short-term outcome and quality of life are of
      overriding importance for the geriatric patient.

PMID- 15981045
TI  - Early enteral feeding by nasoenteric tubes in patients with perforation
      peritonitis.
AB  - Malnutrition is well recognized as a potential cause of increased morbidity and
      mortality in surgical patients. Early postoperative enteral nutrition through a
      feeding jejunostomy has been shown to improve results in patients undergoing
      major resections for gastrointestinal malignancies, trauma, and perforation
      peritonitis. We conducted a prospective study to assess the feasibility and short
      term efficacy of early enteral feeding through a nasoenteric tube placed
      intraoperatively in patients with nontraumatic perforation peritonitis with
      malnutrition. One hundred patients with nontraumatic perforation peritonitis with
      malnutrition undergoing exploratory laparotomy were randomly divided into a test
      group (TG) and a control group (CG) of 50 patients each. TG patients had a
      nasoenteric tube placed at the time of surgery and were started on an enteral
      feeding regime 24 hours postoperatively. Patients in CG were allowed to eat
      orally once they passed flatus. The differences between the two groups with
      respect to nutritional intake in terms of energy and protein, changes in
      nutritional status as assessed by anthropometric, biochemical, and hematological
      values, amount of nasogastric aspirate, return of bowel motility, and
      complication rates were analyzed. The nasoenteric feeding was well tolerated.
      Total calorie and protein intake in TG was significantly higher than in CG: 981
      vs. 505 kcal (p < 0.01), protein 24 vs. 0 g on day 3 and 1498 vs. 846 kcal (p <
      0.01), protein 44 vs. 23 g (p < 0.01) on day 7, respectively. There was reduction
      in the amount of nasogastric aspirate in TG compared with that in CG: 431 vs. 545
      ml/24 h on day 2 and 301 vs. 440 ml/24 h on day 3, respectively. There was much
      faster recovery of bowel motility in TG than in CG at 3.34 vs. 4.4 days (p <
      0.01). Complications developed in 39 of 50 patients in TG and in 47 of 50 in CG.
      The major complications occurred in 6 patients in TG and 12 patients in CG (p <
      0.05). Patients with perforation peritonitis with malnutrition are likely to
      develop large energy deficits postoperatively, resulting in higher incidence of
      infective complications. Early enteral feeding through a nasoenteric tube is well
      tolerated by these patients and helps to improve energy and protein intake,
      reduces the amount of nasogastric aspirate, reduces the duration of postoperative
      ileus, and reduces the risk of serious complications.

PMID- 15981046
TI  - Is minimal access surgery for cancer associated with immunologic benefits?
AB  - Minimal-access surgical techniques have been shown to be beneficial to patients
      in terms of shorter convalescence, reduced pain, and improved cosmesis. Although
      systemic immune function is better preserved following laparoscopic procedures
      when compared with their respective open approaches, CO2 pneumoperitoneum may
      significantly affect local (i.e., infra-abdominal) cellular immunity by reducing
      regional macrophage function. Results to date are conflicting with regard to the
      impact of closed and open methods on intraabdominal immunity. Impaired cellular
      immunity after CO2 pneumoperitoneum may have significant undesirable intra
      abdominal effects on tumor surveillance after oncological surgery; however, at
      present, there is no clinical evidence to support this position. The VATS
      techniques avoid the use of CO2 insufflation, which may offer some advantages
      from the immune function perspective over laparoscopic procedures accomplished
      with CO2 pneumoperitoneum. Better preservation of early postoperative cellular
      immune function and attenuated disturbance in the inflammatory mediators are
      likely contributing factors to the clinical benefits that follow laparoscopic
      surgery and VATS. Larger multi-center randomized trials are needed to confirm the
      potential benefits of minimal-access surgery on patient survival after cancer
      surgery. Future research should focus on the effects of minimal-access surgery on
      other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be
      important in tumor cell dissemination, deposition, and propagation in the early
      postoperative period. Furthermore, additional searches for other factors or
      mediators, heretofore unrecognized, should be carried out. Such studies will, we
      hope, increase our knowledge and understanding of the impact of surgery on immune
      and other physiologic functions.

PMID- 15981047
TI  - The evolving role of endoscopic treatment for bleeding esophageal varices.
AB  - The treatment of acute and recurrent variceal bleeding is best accomplished by a
      skilled, knowledgeable, and well-equipped team using a multidisciplinary
      integrated approach. Optimal management should provide the full spectrum of
      treatment options including pharmacologic therapy, endoscopic treatment,
      interventional radiologic procedures, surgical shunts, and liver transplantation.
      Endoscopic therapy with either band ligation or injection sclerotherapy is an
      integral component of the management of acute variceal bleeding and of the long
      term treatment of patients after a variceal bleed. Variceal eradication with
      endoscopic ligation requires fewer endoscopic treatment sessions and causes
      substantially less esophageal complications than does injection sclerotherapy.
      Although the incidence of early gastrointestinal rebleeding is reduced by
      endoscopic ligation in most studies, there is no overall survival benefit
      relative to injection sclerotherapy. Simultaneous combined ligation and
      sclerotherapy confers no advantage over ligation alone. A sequential staged
      approach with initial endoscopic ligation followed by sclerotherapy when varices
      are small may prove to be the optimal method of reducing variceal recurrence.
      Overall, current data demonstrate clear advantages for using ligation in
      preference to sclerotherapy. Ligation should therefore be considered the
      endoscopic treatment of choice in the treatment of esophageal varices.

PMID- 15981053
TI  - Evidence-based guidelines?

PMID- 15981054
TI  - Patterns of surveillance practices after curative surgery for colorectal cancer
      in a French population.
AB  - PURPOSE: Despite controversies, postoperative surveillance of colorectal cancer
      is generally recommended. This registry-based study was designed to assess the
      adherence of surveillance practices to French guidelines and identify three-year
      surveillance patterns and their demographic and clinical determinants. METHODS:
      All patients (N = 409) diagnosed with first colorectal cancer in 1998 and alive
      without recurrence at least six months after curative surgery were identified
      from a population-based registry. Medical charts from multiple sources were
      reviewed to collect exhaustive information on follow-up procedures used during a
      three-year period. Multiple correspondence and cluster analyses were used to
      identify surveillance patterns. RESULTS: The proportion of patients with a lower
      surveillance than that recommended was 35 percent for clinical examination, 65
      percent for abdominal ultrasound, 52 percent for chest x-ray, and 20 percent for
      colonoscopy. Cluster analysis identified three patterns called minimal, moderate,
      and intensive surveillance patterns, which included 47, 24, and 29 percent of the
      patients respectively. The main independent predictors of both moderate and
      intensive surveillance patterns vs. minimal pattern were advanced tumor stage,
      chemotherapy, and radiation therapy. Younger age also was strongly associated
      with the intensive surveillance pattern, and the presence of symptoms with the
      moderate surveillance pattern. CONCLUSIONS: Adherence of surveillance practices
      to French guidelines seems relatively poor. Surveillance patterns are mainly
      explained by patient age, tumor stage, and treatment modalities.

PMID- 15981055
TI  - Mucosal flap excision for treatment of remnant prolapsed hemorrhoids or skin tags
      after stapled hemorrhoidopexy.
AB  - Stapled hemorrhoidopexy may leave residual skin tags or external components
      following its use in large prolapsed piles. Excision of redundant mucosa above
      the dentate line and reconstitution to the staple line reduces these prolapsed
      elements. We describe a novel technique that removes residual skin tags and piles
      while remaining true to the spirit of stapled hemorrhoidopexy.

PMID- 15981056
TI  - Long-term results of Delorme's procedure and Orr-Loygue rectopexy to treat
      complete rectal prolapse.
AB  - PURPOSE: The aim of this study was to assess long-term outcome of Orr-Loygue
      rectopexy and Delorme's procedures in total rectal prolapse management. METHODS:
      Data were collected retrospectively from 1978 to 2001. Statistical analysis was
      performed by chi-squared test and Student's t -test. RESULTS: One hundred nine
      patients underwent either a Orr-Loygue rectopexy (49 patients) or a Delorme's
      procedure (60 patients). Mean follow-up was 88 (range, 1-300) months. In the
      rectopexy group, the overall complication rate and the recurrence rate were 33
      percent and 4 percent, respectively. In patients with preoperative constipation,
      this symptom was improved or completely resolved in 33 percent and worsened in 58
      percent postoperatively. Seventy-three percent of patients with preoperative
      incontinence were continent or had continence improvement postoperatively. In
      Delorme's group, overall complication and recurrence rates were 15 percent and 23
      percent, respectively. Mortality was 7 percent. In patients with preoperative
      constipation, this symptom was improved or completely resolved in 54 percent and
      worsened in 12.5 percent of patients postoperatively. Forty-two percent of
      patients with preoperative incontinence were continent or had continence
      improvement postoperatively. CONCLUSIONS: In this study, Orr-Loygue rectopexy had
      a lower long-term recurrence rate. However, this surgical procedure is associated
      with a higher complication rate. We believe that Delorme's procedure is still a
      valuable option in selected patients with postoperative minimal morbidity but
      higher recurrence rate.

PMID- 15981057
TI  - Impaired proximal colonic motor response to rectal mechanical and chemical
      stimulation in obstructed defecation.
AB  - PURPOSE: Both motor and sensory dysfunction have been implicated in the
      pathogenesis of obstructed defecation. We have found that despite preservation of
      a defecatory urge, patients with obstructed defecation have lost the normal
      predefecatory augmentation in frequency and amplitude of colonic propagating
      pressure waves. This observation might be explainable by either altered rectal
      sensory thresholds or by dysfunction in the colonic motor apparatus. By measuring
      rectal sensory thresholds and proximal colonic motor responses to rectal
      mechanical and chemical stimuli, we tested the hypotheses that central perception
      of rectal stimuli is enhanced and that the proximal colonic motor response to
      rectal stimulation is attenuated. METHODS: In seven patients with obstructed
      defecation and ten healthy volunteers we measured proximal colonic motor
      responses and sensory thresholds in response to both rectal balloon distention
      and rectal instillation of chenodeoxycholic acid. RESULTS: In controls, but not
      in patients, rectal mechanical distention significantly reduced and chemical
      stimulation significantly increased the frequency of proximal colonic propagating
      sequences (P = 0.01). There was no significant difference in rectal sensory
      thresholds between patients and controls. Prior instillation of chenodeoxycholic
      acid significantly reduced (P < 0.03) maximum tolerated balloon volume and
      defecatory urge volume to comparable degree in both patients and controls.
      CONCLUSIONS: In obstructed defecation, 1) the normal rectocolonic pathways
      mediating stimulation-induced proximal colonic propagating pressure waves are
      nonfunctioning, and. 2) central perception of these rectal stimuli is normal.

PMID- 15981058
TI  - Short-pouch and low-anastomosis Duhamel procedure results in better fecal control
      and normal defecation pattern.
AB  - PURPOSE: The purpose of this study was to analyze the long-term outcome of the
      short-pouch and low-anastomosis Duhamel procedure and to evaluate the quality of
      life after pull-through. We also tried to answer the questions: Does the modified
      Duhamel procedure produce fecal continence? Is the quality of life correlated to
      normal bowel function (1-3 per day) without the use of laxatives? MATERIALS AND
      METHODS: Between January 1993 and January 2002, 53 patients, 44 (83 percent)
      males and 9 (17 percent) females, who underwent a Duhamel procedure were assessed
      retrospectively. Of the 53 children, 36 (67.9 percent) underwent a primary
      Duhamel procedure at our institute (Group A). Seventeen (32.1 percent) patients
      had a primary Duhamel pull-through and subsequently a stoma before a redo
      modified Duhamel procedure (Group B). The technical modification was creation of
      a short rectal pouch of 35 mm, achieving a low colorectal anastomosis 0.5 cm from
      or on the dentate line. All 53 patients were assessed prospectively by a disease
      specific questionnaire. The total score provided a single index of the quality of
      life associated with fecal continence. RESULTS: For Group A (n = 36), the mean
      period of follow-up was 71.4 +/- 29 months. Constipation was seen in four (11.1
      percent) patients. In two (5.6 percent) patients there was a mild degree of
      soiling. Sensation and urge to defecate was intact in 34 (94.4 percent) children
      who could wait to go to the toilet until it was socially convenient. For Group B
      (n = 17), the mean period of follow-up was 73.9 +/- 31.2 months. Constipation
      occurred in 17 (100 percent), encopresis in 14 (82.4 percent), and enterocolitis
      in 15 (88.2 percent) after the primary Duhamel procedure. In comparison, there
      was complete absence of constipation (100 percent), encopresis (100 percent), and
      complete resolution of enterocolitis (100 percent) after the redo modified
      Duhamel (P = 0.001). Continence to solid stools after primary Duhamel was seen in
      5 (29.4 percent) vs. 17 (100 percent) after redo modified Duhamel. After the redo
      modified Duhamel all 17 (100 percent) patients have retained the sensation and
      urge to defecate and 15 (88.2 percent) can wait to get to the toilet until it is
      socially convenient. In all 53 patients, the quality of life was good in 86.8
      percent (46/53) and correlated directly with fecal continence (r = 0.977). There
      was no correlation between age of patient and fecal continence (r = 0.597) and
      rate of fecal incontinence did not decrease with age. Direct correlation was seen
      with the presence of constipation and the incidence of late onset enterocolitis
      (r = 0.942). CONCLUSIONS: Short-pouch, low-anastomosis Duhamel pull-through
      procedure results in fecal continence and complete emptying. The above procedure
      has a positive impact on the quality of life in these children.

PMID- 15981059
TI  - Sitz bath: where is the evidence? Scientific basis of a common practice.
AB  - PURPOSE: This study was designed to determine if evidence exists to justify and
      support the recommendation of sitz bath in the management of anorectal disorders.
      METHODS: A Medline search was conducted using the key words "sitz bath" and "hot
      bath." RESULTS: Thirty-six articles were found which highlighted the physiology,
      benefits, risks, complications, and techniques of sitz bath. Most of the studies
      were published in gynecologic or nursing journals. One randomized study comparing
      sitz bath to placebo was found. Two articles speculated that sitz bath induces
      relaxation of the internal sphincter muscle. Cold sitz bath was reported to
      decrease perineal edema more than warm sitz bath, although patients tended to
      prefer the latter. Five articles reported complications of sitz bath, including
      dissemination of herpes, maternal-neonatal Streptococcus outbreak, and skin
      burns. CONCLUSION: A review of the literature demonstrated a lack of scientific
      data to support the use of sitz bath in the treatment of anorectal disorders.
      Additional randomized and controlled clinical studies are needed to investigate
      whether this time consuming recommendation is beneficial to patients.

PMID- 15981060
TI  - A comparison of open vs. laparoscopic abdominal rectopexy for full-thickness
      rectal prolapse: a meta-analysis.
AB  - PURPOSE: Using meta-analytical techniques, this study was designed to compare
      open and laparoscopic abdominal procedures used to treat full-thickness rectal
      prolapse in adults. METHODS: Comparative studies published between 1995 and 2003,
      cited in the literature of open abdominal rectopexy vs. laparoscopic abdominal
      rectopexy, were used. The primary end points were recurrence and morbidity, and
      the secondary end points assessed were operative time and length of hospital
      stay. A random effect model was used to aggregate the studies reporting these
      outcomes, and heterogeneity was assessed. RESULTS: Six studies, consisting of a
      total of 195 patients (98 open and 97 laparoscopic) were included. Analysis of
      the data suggested that there is no significant difference in recurrence and
      morbidity between laparoscopic abdominal rectopexy and open abdominal rectopexy.
      Length of stay was significantly reduced in the laparoscopic group by 3.5 days
      (95 percent confidence interval, 3.1-4; P < 0.01), whereas the operative time was
      significantly longer in this group, by approximately 60 minutes (60.38 minutes;
      95 percent confidence interval, 49-71.8). CONCLUSIONS: Laparoscopic abdominal
      rectopexy is a safe and feasible procedure, which may compare equally with the
      open technique with regards to recurrence and morbidity and favorably with length
      of stay. However large-scale randomized trials, with comparative, sound
      methodology are still needed to ascertain detailed outcome measures accurately.

PMID- 15981061
TI  - Long-term consequences of first vaginal delivery-induced anal sphincter defect.
AB  - PURPOSE: This study was designed to investigate the long-term consequences of
      anal sphincter defects detected after a first vaginal delivery. METHODS: A cohort
      of 197 primiparous females was evaluated for anal continence and anal sphincter
      defects in 1997. In June 2003 (6 years later), a postal questionnaire was sent to
      74 females of this cohort, and answers from 54 (73 percent) were analyzed.
      RESULTS: In 1997, a transanal ultrasound found 66 anal sphincter defects (33.5
      percent). Twenty-one females (10.6 percent) had persistent signs of anal
      incontinence 12 weeks after the index delivery. There was a significant
      correlation between the presence of anal sphincter defect and anal incontinence.
      Six years later, 11 of 54 females reported signs of anal incontinence: 50 percent
      of females with anal sphincter defect and only 8.1 percent of females without (P
      = 0.002). Large defects were more frequently associated with anal incontinence.
      Anal incontinence after the index vaginal delivery also was significantly
      associated with anal incontinence six years later. Multivariate analysis showed
      anal sphincter defect to be the only variable predictive of anal incontinence
      (odds ratio, 10.5; 95 percent confidence interval, 2.1-52.4). CONCLUSIONS: Anal
      sphincter defects detected after the first vaginal delivery appear as the main
      risk factor for anal incontinence six years later.

PMID- 15981062
TI  - Management of rectal prolapse in children.
AB  - PURPOSE: Rectal prolapse in children is not uncommon and usually is a self
      limiting condition in infancy. Most cases respond to conservative management;
      however, surgery is occasionally required in cases that are intractable to
      conservative treatment. This study was designed to analyze the outcomes of rectal
      prolapse in children and to propose a pathway for the management of these cases
      in children. METHODS: A retrospective analysis of all cases of rectal prolapse
      referred to our surgical unit during a period of five years was performed. End
      point was recurrence of prolapse requiring manual reduction under sedation or an
      anesthetic. Results are presented as median (range) and statistical analysis was
      performed using chi-squared test; P < 0.05 was considered significant. RESULTS: A
      total of 49 children (25 males) presented with symptoms of rectal prolapse at a
      median age of 2.6 years (range, 4 months -10.6 years). All children received an
      initial period of conservative treatment with watchful expectancy and/or
      laxatives. Twenty-five patients were managed conservatively without any
      additional procedures (Group A), and 24 patients had one or more interventions,
      such as injection sclerotherapy, Thiersch procedure, anal stretch, banding of
      prolapse, and rectopexy (Group B). Management of rectal prolapse was successful
      with no recurrences in 24 patients (96 percent) in Group A vs. 15 patients (63
      percent) in Group B at a median follow-up period of 14 (range, 2-96) months. An
      underlying condition was found in 84 percent of patients in Group A vs. 54
      percent in Group B (P = 0.024). The age at presentation was younger than four
      years in 88 percent of patients in Group A vs. 58 percent in Group B (P = 0.019).
      CONCLUSIONS: Rectal prolapse in children does respond to conservative management.
      A decision to operate is based on age of patient, duration of conservative
      management, and frequency of recurrent prolapse (>2 episodes requiring manual
      reduction) along with symptoms of pain, rectal bleeding, and perianal excoriation
      because of recurrent prolapse. Those cases presenting younger than four years of
      age and with an associated condition have a better prognosis. The authors propose
      an algorithm for the management of rectal prolapse in children.

PMID- 15981063
TI  - Bowel preparation is associated with spillage of bowel contents in colorectal
      surgery.
AB  - PURPOSE: Infectious complications pose a significant cause of morbidity in colon
      and rectal surgery. This study was designed to assess the effect of bowel
      preparation on spillage of bowel contents into the peritoneal cavity during
      colorectal surgery, and its potential effect on the rate of postoperative
      infectious complications. METHODS: The quality of bowel preparation and the
      incidence of spillage of bowel contents were prospectively assessed in patients
      undergoing elective colon and rectal resection. The patients were followed for 30
      days for postoperative infectious and noninfectious complications. RESULTS: A
      total of 333 patients were included in this study, of which 181 did not receive
      mechanical bowel preparation. Intraoperative spillage of bowel contents occurred
      in 48 patients (14 percent), whereas in 285 patients (86 percent), spillage did
      not occur. There was a trend toward a higher rate of overall surgical infectious
      and noninfectious complications in patients who had spillage of bowel contents
      compared with patients without spillage; however, this difference was not
      statistically significant (18.7 vs. 11 percent, and 29 vs. 19 percent,
      respectively). Preoperative mechanical bowel preparation and colocolonic or
      colorectal anastomosis was associated with a higher rate of bowel contents
      spillage, although this difference did not reach statistical significance. Liquid
      colonic contents caused significantly higher rates of spillage. CONCLUSIONS:
      Spillage of bowel contents into the peritoneal cavity during colon and rectal
      surgery may increase the rate of postoperative infectious complications. In
      addition, inadequate mechanical bowel preparation, leading to liquid bowel
      contents, increases the rate of intraoperative spillage.

PMID- 15981064
TI  - Delayed treatment for rectal cancer.
AB  - PURPOSE: Reports of the relationship between length of delay before diagnosis of
      rectal cancer and stage of the disease have been mixed. The present study
      documented the magnitude and medical ramifications of delay in diagnosing rectal
      cancer. METHODS: One hundred twenty patients who had been recently diagnosed with
      rectal cancer provided information regarding history of symptoms and initial
      perceptions of those symptoms. Patients also estimated the time elapsed from
      onset of symptoms until their first consultation with a physician, as well as
      time elapsed from consultation until the diagnosis of rectal cancer was made.
      Stage information was gathered from patient charts. RESULTS: For 106 of the
      patients, the first sign of rectal cancer was in the form of symptoms, and the
      most common first symptom was rectal bleeding. For the remaining 14 patients,
      their cancer was first discovered through routine examination. Over 75 percent of
      patients with symptoms did not initially believe that they were caused by cancer
      or any other serious problem, and over 50 percent attributed their symptoms to
      hemorrhoids. There was a clear trend, albeit statistically nonsignificant, toward
      worsening disease with longer delays. Median delay times in weeks were Stage I
      (10.0 weeks), Stage II (14.0 weeks), Stage III (18.5 weeks), and Stage IV (26.0
      weeks). CONCLUSIONS: Delayed diagnosis for rectal cancer remains a significant
      problem, with instances of delay attributable to both patient and physician.
      Delayed diagnosis can result in more serious disease and, when attributable to
      the physician, can result in damaged trust and sometimes legal action.

PMID- 15981065
TI  - Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial
      in elective open colon surgery.
AB  - PURPOSE: Mechanical bowel preparation is common practice in elective colon
      surgery. In recent literature the value of this procedure is under discussion. To
      verify the value of mechanical bowel preparation in elective open colon surgery,
      a randomized clinical trial was conducted. METHODS: During a prospective,
      multicenter, randomized study, 250 patients undergoing elective open colon
      surgery were randomized between receiving mechanical bowel preparation with
      polyethylene glycol (PEG group, 125 patients) and having a normal meal
      preoperatively (normal meal preoperatively group, 125 patients). Outcome
      parameters were wound infection with bacterial results of intraoperative swabs
      and anastomotic leak. RESULTS: In the polyethylene glycol group there were a
      total of nine wound infections (7.2 percent) and seven anastomotic leaks (5.6
      percent) compared with seven wound infections (5.6 percent) (P = 0.61) and six
      anastomotic leaks (4.8 percent) (P = 0.78) in the normal meal preoperatively
      group. Bacterial results showed 52 percent sterile subcutis swabs in the PEG
      group and 63 percent sterile subcutis swabs in the normal meal preoperatively
      group (P = 0.11). CONCLUSION: In the present study we could not detect a
      difference in outcome parameters between patients receiving mechanical bowel
      preparation in elective open colon surgery and patients without preoperative
      treatment of the bowel. The present study, although underpowered, did not show a
      difference in the primary outcome of bacterial wound cultures between patients
      receiving preoperative mechanical bowel preparation and patients receiving no
      preoperative bowel treatment. We conclude that there may be no need to continue
      the use of mechanical bowel preparation in elective open colon surgery.

PMID- 15981066
TI  - Gastrointestinal symptoms in spinal cord injury: relationships with level of
      injury and psychologic factors.
AB  - INTRODUCTION: Previous surveys of gastrointestinal symptoms after spinal cord
      injury have not used validated questionnaires and have not focused on the full
      spectrum of such symptoms and their relationship to factors, such as level of
      spinal cord injury and psychologic dysfunction. This study was designed to detail
      the spectrum and prevalence of gastrointestinal symptoms in spinal cord injury
      and to determine clinical and psychologic factors associated with such symptoms.
      METHODS: Established spinal cord injury patients (>12 months) randomly selected
      from a spinal cord injury database completed the following three questionnaires:
      1) Rome II Integrative Questionnaire, 2) Hospital Anxiety and Depression Scale,
      and 3) Burwood Bowel Dysfunction after spinal cord injury. RESULTS: A total of
      110 patients participated. The prevalence of abdominal bloating and constipation
      were 22 and 46 percent, respectively. Bloating was associated with cervical (odds
      ratio = 9.5) and lumbar (odds ratio = 12.1) level but not with thoracic level of
      injury. Constipation was associated with a higher level of injury (cervical odds
      ratio = 5.6 vs. lumbar) but not with psychologic factors. In contrast, abdominal
      pain (33 percent) and fecal incontinence (41 percent) were associated with higher
      levels of anxiety (odds ratio = 6.8, and odds ratio = 2.4) but not with the level
      of injury. CONCLUSIONS: There is a high prevalence and wide spectrum of
      gastrointestinal symptoms in spinal cord injury. Abdominal bloating and
      constipation are primarily related to specific spinal cord levels of injury,
      whereas abdominal pain and fecal incontinence are primarily associated with
      higher levels of anxiety. Based on our findings, further physiologic and
      psychologic research studies in spinal cord injury patients should lead to more
      rational management strategies for the common gastrointestinal symptoms in spinal
      cord injury.

PMID- 15981068
TI  - Tumors of the retrorectal space.
AB  - PURPOSE: Retrorectal tumors are a diverse group of masses derived from a variety
      of embryologic origins. Because of this, some confusion is associated with their
      diagnosis and management. Although rare, a basic understanding of the etiology,
      presentation, work-up, and treatment of retrorectal masses is essential. METHODS:
      The incidence, classification, diagnosis, treatment, and prognosis of these
      masses are presented. A comprehensive review of the literature is included in our
      analysis. RESULTS: Retrorectal lesions can be classified as congenital,
      inflammatory, neurogenic, osseous, or miscellaneous. Benign and malignant lesions
      behave similarly. The most common presentation is an asymptomatic mass discovered
      on routine rectal examination, but certain nonspecific symptoms can be elicited
      by careful history. Biopsy of these lesions should be avoided to prevent tumor
      seeding, fecal fistula, meningitis, and abscess formation. Complete surgical
      resection, usually after appropriate specialized imaging, remains the cornerstone
      of their treatment. Three approaches commonly used for resection are abdominal,
      transsacral, or a combined abdominosacral approach. Prognosis is directly related
      primarily to local control, which often is difficult to achieve for malignant
      lesions. CONCLUSIONS: Retrorectal masses present a challenging surgical problem
      from diagnosis to treatment. A high index of suspicion and resultant early
      diagnosis, followed by thorough preoperative planning, is required for optimal
      management and outcome.

PMID- 15981069
TI  - Integrity of the anal sphincters after pouch-anal anastomosis: evaluation with
      three-dimensional endoanal ultrasonography.
AB  - PURPOSE: The aim of the present study was to assess the integrity of the anal
      sphincters after handsewn pouch-anal anastomosis performed with the help of a
      Scott retractor. For this purpose the anal sphincters were visualized with three
      dimensional endoanal ultrasonography. METHODS: Patients undergoing a colonic
      pouch-anal anastomosis or an ileal pouch-anal anastomosis were included. Before
      and six months after the procedure, the length and volume of both sphincters were
      assessed with three-dimensional endoanal ultrasonography, and anal manometry was
      performed. Continence scores were determined using the Fecal Incontinence
      Severity Index (FISI). RESULTS: Fifteen patients with a colonic pouch and 13
      patients with an ileal pouch were examined. Six months after the procedure, three
      dimensional endoanal ultrasonography showed significant alterations of the
      internal anal sphincter in eight patients with a colonic pouch-anal anastomosis
      (53 percent) and in eight patients with an ileal pouch-anal anastomosis (62
      percent). These alterations were characterized by asymmetry or thinning. No
      defects were seen in the colonic pouch group, but, in two patients with an ileal
      pouch, a small defect in the internal anal sphincter was found. A decrease in
      internal anal sphincter volume was seen only in patients with a colonic pouch
      anal anastomosis (P = 0.009). In both groups the length of the internal anal
      sphincter and the length, thickness, and volume of the external anal sphincter
      remained the same. After the procedure a reduction of maximum anal resting
      pressure was found in both groups (colonic pouch: P < 0.001, ileal pouch: P =
      0.001). Maximum anal squeeze pressure was reduced in only patients with an ileal
      pouch-anal anastomosis (P = 0.006). The observed alterations of the internal anal
      sphincter and the manometric findings showed no correlation with the
      postoperative Fecal Incontinence Severity Index scores. CONCLUSION: Handsewn
      pouch-anal anastomosis, performed with the help of a Scott retractor, only rarely
      leads to internal anal sphincter defects, but three-dimensional endoanal
      ultrasonography shows alterations of the internal anal sphincter in 57 percent of
      the patients. No correlation was observed between these alterations and the
      functional outcome.

PMID- 15981070
TI  - Perspectives on vacuum-assisted closure therapy in pilonidal sinus surgery.

PMID- 15981071
TI  - Is routine cavity drainage necessary in Karydakis flap operation? A prospective,
      randomized trial.
AB  - PURPOSE: Different surgical techniques for pilonidal disease have been described
      in the literature. In this study our aim was to evaluate the influence of routine
      cavity drainage in the Karydakis flap technique. METHODS: Fifty patients with
      pilonidal sinus who underwent the Karydakis flap operation were evaluated
      prospectively. The patients were assigned randomly into two groups-with and
      without suction drainage of the cavity-and the effects of drains were studied in
      terms of wound complications, hospital stay, and recurrence rate. RESULTS: There
      was no significant difference between groups in term of length of hospital stay.
      Complication rate was 20 percent and the complications were caused exclusively by
      fluid collections. Wound infection, dehiscence, or failure was not observed in
      any of the patients. There has been no recurrence in any of the patients during
      the follow-up period. There was a significant increase in the number of fluid
      collections in patents without a suction drain. CONCLUSION: The present study
      indicates that routine cavity drainage reduces the incidence of fluid collection
      after the Karydakis flap operation.

PMID- 15981072
TI  - Age and colorectal cancer with focus on the elderly: trends in relative survival
      and initial treatment from a Danish population-based study.
AB  - PURPOSE: Elderly patients with colorectal cancer undergo surgery with curative
      intent less frequently than younger patients, and survival declines with
      increasing age. We compared relative survival of colorectal cancer among patients
      older than 75 years with that of younger patients in Denmark during the period
      1977 to 1999. We also examined trends in choice of initial treatment. METHODS:
      From the files of the nationwide population-based Danish Cancer Registry, we
      identified all cases of colorectal cancer diagnosed between 1977 and 1999. We
      then linked this data to information on survival obtained from the Danish
      Register of Causes of Death and from the Central Population Register. RESULTS:
      During the entire study period, short-term and long-term relative survival
      improved for patients of all ages, but the improvement was more pronounced among
      elderly patients (>75 years). Radical resection was increasingly chosen as the
      initial treatment for elderly patients; during the 1995 to 1999 period it was
      performed on approximately 50 percent of such patients, almost as frequently as
      among younger patients. CONCLUSIONS: Relative survival of elderly colorectal
      cancer patients (>75 years) improved in Denmark between 1977 and 1999. In the
      most recent period studied, 1995 to 1997, only minor differences in five-year
      relative survival were observed among younger, middle-aged, and elderly patients.
      A simultaneous increase in the rate of radical resection among elderly patients,
      reflecting more effective treatment, may underlie this finding.

PMID- 15981075
TI  - Avoiding overtreatment with day-case hemorrhoidopexy.

PMID- 15981077
TI  - The bioavailability of polyphenols is highly governed by the capacity of the
      intestine and of the liver to secrete conjugated metabolites.
AB  - BACKGROUND: After ingestion of a complex meal containing foods and beverages of
      plant origin, different polyphenols are likely to be simultaneously present in
      the intestine. However, almost nothing is known about their interactions and
      possible consequences on their bioavailability. AIM OF THE STUDY: The present
      study deals with the intestinal absorption and splanchnic metabolism of three
      polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the
      small intestine alone or in combination, at different doses (15 and 120 microM).
      METHODS: The fate of polyphenols in the small intestine was studied using a rat
      in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile
      and plasma by HPLC. RESULTS: Whatever the perfused dose, the efficiency of the
      net transfer towards the enterocyte was similar for the three polyphenols and not
      significantly modified by any association between these molecules. However, FA
      largely differed from the two flavonoids by its low intestinal secretion of
      conjugates. When perfused at 15 microM, the secretion of conjugates back to the
      lumen represented 6.2% of the net transfer into the enterocytes for FA compared
      to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal
      conjugation and secretion of conjugates back to the gut lumen varied with the
      dose of flavonoids: saturation of conjugation was observed for the highest dose
      or when a high dose of a second flavonoid was perfused simultaneously. Intensity
      of the biliary secretion substantially differed among tested polyphenols: 7.7% of
      the net transfer for FA vs 50% for genistein or hesperetin. The extent of the
      enterohepatic cycling of these polyphenols was proportional to the perfused dose
      and unaffected by the simultaneous presence of different compounds in the
      intestine. CONCLUSION: Genistein and hesperetin appeared less available than FA
      for peripheral tissues because of a high intestinal and biliary secretion of
      their conjugates. Moreover, data suggest that a high polyphenol intake may
      improve their bioavailability due to saturation of the intestinal secretion of
      conjugates.

PMID- 15981079
TI  - MRI evaluation of the basal ganglia size and iron content in patients with
      Parkinson's disease.
AB  - OBJECTIVE: To evaluate by MRI the area size and the degree of iron accumulation
      in basal ganglia nuclei that are implicated in the pathogenesis of Parkinson's
      disease (PD). METHODS: 40 patients with idiopathic PD and 40 controls were
      examined on a 1. 5 Tesla MR imager, using a multiecho SE sequence 2000/20, 40,
      60, 80, 100, 120, 140, 160 (TR/TE). The T2 relaxation time (T2) and the area of
      substantia nigra zona compacta (SNc), substantia nigra zona reticulata (SNr),
      putamen (Pu), globus pallidus external (GPe), globus pallidus internal (GPi),
      caudate nucleus (CN), locus coeruleus (LC) and subthalamic nucleus (STN) were
      assessed. RESULTS: The T2 of SNc (76. 8 +/- 6. 0) was lower and of Pu (79.5 +/-
      6.0) and GPe (69.5 +/- 7.0) was higher in patients than in controls (78.6 +/-
      3.8, 77.4 +/- 3.9 and 67.3 +/- 5.7, respectively), p < 0.05. The area of CN
      (125.9 +/- 20.2) and Pu (201.5 +/- 48.7) was higher in patients than in controls
      (110.7 +/- 21.5 and 180.1 +/- 41.1, respectively), p < 0.05. A more pronounced
      decrease in the T2 of SNc (73.6 +/- 8.9) was observed when the more affected side
      of patients was evaluated separately. In patients with disease duration > 5 years
      the T2 of STN (71.5 +/- 6.3) was lower and the area of Pu was higher (215.3 +/-
      54.9) compared with those with disease duration < or = 5 years (75.8 +/- 10.9 and
      190.9 +/- 41.0 respectively), p < 0.05. CONCLUSIONS: These findings suggest that
      dysfunction of the basal ganglia circuitry in PD may affect iron content not only
      in SNc but in STN, Pu and GPe as well. Compensatory sprouting of the remaining
      dopaminergic fibers could account for the increased area of the CN and Pu.

PMID- 15981080
TI  - SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not
      account for intrafamilial variability in siblings.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects
      motor neurons. It is caused by mutations in the survival motor neuron gene 1
      (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present
      in all the patients, is unable to prevent the disease. An SMN2 dosage method was
      applied to 45 patients with the three SMA types (I-III) and to four pairs of
      siblings with chronic SMA (II-III) and different phenotypes. Our results confirm
      that the SMN2 copy number plays a key role in predicting acute or chronic SMA.
      However, siblings with different SMA phenotypes show an identical SMN2 copy
      number and identical markers, indicating that the genetic background around the
      SMA locus is insufficient to account for the intrafamilial variability. In our
      results, age of onset appears to be the most important predictor of disease
      severity in affected members of the same family. Given that SMN2 is regarded as a
      target for potential pharmacological therapies in SMA, the identification of
      genetic factors other than the SMN genes is necessary to better understand the
      pathogenesis of the disease in order to implement additional therapeutic
      approaches.

PMID- 15981081
TI  - Femoral neuropathy induced by a low-grade myofibroblastic sarcoma of the groin.

PMID- 15981082
TI  - Progressive MRI abnormalities in late recurrence of Sydenham's chorea.
AB  - We report four cases of adult recurrence of Sydenham's chorea (SC). The first
      episodes all followed childhood tonsillopharyngitis. Many years later, subsequent
      episodes appeared after the triggering circumstances: throat or cutaneous
      infection, pregnancy, childbirth, contraceptive treatment or stress. Other
      inflammatory diseases were ruled out and streptococcal serology was weakly
      positive. Magnetic Resonance Imaging (MRI) revealed focal areas of T2 hypersignal
      in the caudate nucleus, the pallidum, the putamen and the white matter. One year
      later, repeat MRI variously gave evidence of the persistence, disappearance or
      even new appearance of abnormalities. Specific features of SC recurrence in the
      adult may include: a personal history of chorea after a throat infection during
      childhood; a second episode of isolated chorea with or without slight
      neuropsychological disorders; streptococcal serology weakly positive; focal
      hypersignals involving the basal ganglia; the triggering circumstances. Since SC
      is considered to be an autoimmune disease, the progressive MRI abnormalities
      suggest that certain circumstances may trigger the reactivation of persistent
      immune disorders.

PMID- 15981083
TI  - Association between circulating levels of the novel TNF family members APRIL and
      BAFF and lymphoid organization in primary Sjogren's syndrome.
AB  - B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are
      members of the tumour necrosis factor superfamily. We have examined circulating
      BAFF and APRIL in relation to serological deviations and lymphoid organization in
      the salivary glands of the chronic, autoimmune disorder Sjogren's syndrome.
      Lymphoid organization in the shape of ectopic germinal centers were detected in
      33 of 130 consecutive minor salivary gland biopsies and coincided with increased
      focus score and elevated levels of serum IgG. Follicular dendritic cell networks,
      proliferation of mononuclear cells and altered B/T cell ratio also separated the
      two subgroups. Serum levels of sBAFF and sAPRIL were increased in Sjogren's
      syndrome compared to healthy blood donors, especially in anti-Ro/La+ patients.
      Though the differences could not be related to germinal center formation,
      positive correlations between serum levels of sBAFF and sAPRIL, focus score and
      IgG denotes their possible role in the disease progression of primary Sjogren's
      syndrome.

PMID- 15981084
TI  - Evaluation of a new fluorescent-enzyme immuno-assay for diagnosis and follow-up
      of ANCA-associated vasculitis.
AB  - In this study we have evaluated a new, fully automated fluorescent-enzyme immuno
      assay (FEIA) for detection and quantification of anti-PR3 and anti-MPO ANCA in
      diagnosis and follow-up of ANCA-associated small vessel vasculitis (AAV). PR3-
      and MPO-ANCA were determined by FEIA technology in (1) sera of 87 consecutive
      patients with biopsy-proven, pauci-immune necrotizing crescentic
      glomerulonephritis (NCGN) and 72 controls; (2) 120 sera (60 patients with
      Wegener's granulomatosis and 60 controls) that were previously used in a
      multicentre comparison of direct and capture ELISAs for PR3-ANCA; (3) in samples
      preceding relapse in 23 PR3-AAV patients with and 23 matched PR3-AAV patients
      without relapse for prediction of relapses. PR3- and/or MPO-ANCA detection in
      pauci-immune NCGN by FEIA revealed an overall sensitivity of 82.8%. The FEIA
      specificity was 96% and 100% for PR3- and MPO-ANCA, respectively. The overall
      sensitivity of MPO- and PR3-ANCA could be increased to 88.5% by lowering the cut
      off values without affecting the specificity (ROC-curve analysis), which is
      similar to a multistep ANCA procedure that combines indirect immunofluorescence
      with direct and capture ELISAs. The sensitivity for Wegener's granulomatosis (WG)
      of the PR3-ANCA FEIA (60%) was more comparable to direct ELISAs (64%) than to
      capture ELISAs (74%). A rise of 100% in ANCA level as measured by FEIA appeared
      optimal (ROC-curve) for prediction of relapses and such a rise was observed in 26
      patients. In 18 of these 26 patients the rise was followed by a relapse (PPV
      69%), whereas in 15 of the 20 patients without a rise no relapse was observed
      (NPV 75%). In conclusion, detection of PR3- and MPO-ANCA by FEIA has excellent
      performance in terms of diagnosis of AAV patients. Furthermore, detection of
      rises in PR3-ANCA by FEIA for prediction of relapses gives results comparable to
      other techniques.

PMID- 15981085
TI  - mRNA quantification of T-bet, GATA-3, IFN-gamma, and IL-4 shows a defective Th1
      immune response in the peripheral blood from rheumatoid arthritis patients: link
      with disease activity.
AB  - A T helper (Th)1 cytokine profile is predominant in the inflamed synovium of
      rheumatoid arthritis (RA). Since the situation in the blood is more
      controversial, we studied the Th1/Th2 balance in the peripheral blood of RA
      patients using mRNA markers. Total RNA was isolated directly from whole blood
      from 20 RA patients and 14 healthy controls. T-bet and GATA-3 transcription
      factors associated with Th1 and Th2 responses respectively, and IFNgamma and IL-4
      mRNA levels were measured by real-time PCR. In RA but not in control samples, T
      bet mRNA levels correlated positively with IFNgamma mRNA levels, and negatively
      with CRP levels. Accordingly, RA patients were divided into two groups according
      to CRP levels. In comparison to RA patients with a low CRP (CRP < 40 mg/l),
      patients with a high CRP (CRP>or=40 mg/l) had lower IFNgamma/beta-actin, T
      bet/beta-actin mRNA levels and T-bet/GATA-3 expression ratios. In conclusion, RA
      blood cells showed a decreased Th1 situation as indicated by low IFNgamma and T
      bet mRNA expression. This pattern was found only in patients with the most active
      disease.

PMID- 15981086
TI  - Involvement of c-Jun N-terminal kinase in rF1 mediated activation of murine
      peritoneal macrophages in vitro.
AB  - Fraction 1 (F1) protein forms a capsule on the surface of Yersinia pestis.
      Recently, we reported rF1-induced activation of macrophages. In current
      investigation, we studied the role of JNK MAPK signal transduction pathway in rF1
      induced activation of macrophages in vitro. SP600125, a specific inhibitor of
      JNK, inhibited JNK MAPK phosphorylation, indicating the specificity of the above
      response. Though, the rF1-induced phosphorylation of JNK MAPK was also inhibited
      by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor genestein
      and PI3-K inhibitor wotmannin. Activation of the transcription factor NF-kB
      (phosphorylation of IkB) and c-Jun was observed in response to rF1 treatment. The
      rF1-induced JNK MAPK activity was correlated to the functional activation of
      macrophages by demonstrating the inhibition of NO, TNF-alpha production and
      microtubule polymerization caused by SP600125. Taken together, the data suggests
      the involvement of JNK MAPK/NF-kB pathway in rF1-induced activation of
      macrophages.

PMID- 15981087
TI  - CD4+ T cells downregulate Bcl-2 in germinal centers.
AB  - Germinal centers (GCs) are the main site of T cell-dependent antibody responses.
      Upon antigen challenge, GCs comprise mostly B cells undergoing proliferation,
      somatic hypermutation and antigen-affinity selection. GC B cells down-modulate
      the expression of Bcl-2 protein and are highly sensitive to apoptosis to
      eliminate autoreactive or low-affinity cells. Bcl-2 is still expressed in a few
      GC cells, whose identity remains unclear. To address this issue, we examined by
      confocal microscopy the expression of Bcl-2 by different GC lymphocyte subsets in
      hyperplastic tonsils. We found that the vast majority of Bcl-2(+) GC cells are T
      lymphocytes. Conversely, while in the mantle zone and in the interfollicular
      areas T cells are almost exclusively Bcl-2(+), in the GC, most T lymphocytes are
      Bcl-2(-). In addition, most of the CD4(+) GC T cells are Bcl-2(-), while nearly
      100% of the CD8(+) GC T cells are Bcl-2(+). The Bcl-2 downregulation by both B
      and CD4(+) T GC cells supports the concept that these two subsets may undergo a
      selection process in this microenvironment.

PMID- 15981088
TI  - Complementary function of gamma delta T-lymphocytes and dendritic cells in the
      response to isopentenyl-pyrophosphate and lipopolysaccharide antigens.
AB  - Dendritic cells and gamma delta T-lymphocytes play a crucial role in the early
      response to microbial infections. Since both dendritic cells and gamma delta T
      lymphocytes may be activated by specific microbial products, we analyzed their
      interplay in the presence of such respective ligands: lipopolysaccharide and
      isopentenyl-pyrophosphate. Activated gamma delta T-cells increased the
      maturational state of dendritic cells induced by lipopolysaccharide, increasing
      the expression of co-stimulatory and MHC class I and II molecules. IL-12
      production by dendritic cells was strongly amplified in the presence of activated
      gamma delta T-cells and the Th1 polarization of naive CD4(+) T-lymphocytes was
      significantly increased. On the other hand, dendritic cells enhanced gamma delta
      T-cell functions induced by isopentenyl-pyrophosphate and promote their IL-2
      independent proliferation through CD86 contact. Altogether, dendritic cells and
      gamma delta T-cells exert a complementary function promoting an optimal immune
      response to non peptidic microbial antigens.

PMID- 15981089
TI  - Different proinflammatory cytokine serum pattern in neonate patients undergoing
      open heart surgery. Relevance of IL-8.
AB  - The purpose of this work was to investigate the clinical significance of serum
      levels of proinflammatory cytokines in pediatric patients undergoing
      cardiopulmonary bypass. We divided the patients in two groups: 8 neonates, and 19
      non-newborn children. IL-1beta, IL-6, IL-8, and TNF serum levels were quantified
      before sternotomy, at admission to the PICU (30 min postoperatively), 24 h after
      the onset of surgery and 3 days after the operation. Surgical cardiac stress
      elicits significant increments of IL-6, IL-8 and TNF serum concentrations in both
      neonates and non-neonates, regardless of their preoperative clinical condition.
      However, in newborns the magnitude of the proinflammatory cytokine increments
      was, in particular with IL-8, remarkably greater than in older children.
      Moreover, neonate and non-neonate patients showed clearly disparate patterns of
      serum concentrations over time of both IL-8 and TNF. There was a marked
      relationship between IL-8 levels and postoperative morbidity, evaluated by
      pulmonary dysfunction, days on inotropic support and days of PICU stay in both
      neonates and non-neonates patients. In contrast, we found no relationship between
      serum levels of IL-6 and TNF and postoperative clinical data. Newborn and non
      newborn patients undergoing cardiopulmonary bypass exhibit dissimilar patterns of
      proinflammatory cytokines. IL-8 might be implicated in the multiorganic
      dysfunction related to cardiopulmonary bypass in pediatric patients.

PMID- 15981090
TI  - TH1/TH2 functional imbalance after acute myocardial infarction: coronary arterial
      inflammation or myocardial inflammation.
AB  - OBJECTIVES: The study clarified whether the T-helper (Th)1/Th2 imbalance existed
      only in coronary arterial inflammation or in both coronary arterial inflammation
      and myocardial inflammation and explored the significance of the imbalance of
      Th1/Th2 function after acute myocardial infarction (AMI). BACKGROUND: There are
      two different inflammatory processes in patients with AMI: the coronary arterial
      inflammation that leads to the pathogenesis of AMI and the myocardial
      inflammation after AMI that leads to ventricular remodeling, which are positively
      and negatively regulated by Th1 and Th2 lymphocytes, respectively. METHODS:
      Peripheral blood mononuclear cells from 33 AMI patients, 22 unstable angina (UA)
      patients and splenocytes from 35 AMI Wistar rats were collected. Cytokine
      producing Th cells were ambulatorily monitored by 3-color flow cytometry.
      Interferon (IFN)-gamma and interleukin (IL)-4 mRNA in the rat myocardium and
      chemokine receptors CCR3,CCR5 and CXCR3 mRNA on the surface of rat T-lymphocytes
      after AMI were measured by RT-PCR. RESULTS: IFN-gamma-producing T-cells
      significantly increased in patients with AMI and UA within 24 hours after the
      onset of symptom. The high ratio of IFN-gamma-producing T-cells recovered 1 week
      after the onset in UA patients, while it could be examined 1 week and even 1
      month after the onset in AMI patients. The up-regulation of Th1 cell function is
      consistent with bad heart function. There was no significant difference on the
      frequencies of IL-4-producing T-cells between each group. 1 week, 2 weeks and 1
      month after AMI, IFN-gamma mRNA increased in the myocardium of rats, but there
      was no significant change on global Th cell functions. CONCLUSIONS: Th1/Th2
      functional imbalance exists in both coronary arterial inflammation and myocardial
      inflammation processes. The up-regulation of Th1 cell-functions may participate
      in the immune-mediated ventricular remodeling after AMI.

PMID- 15981092
TI  - Post-natal ontogenesis of the T-cell receptor CD4 and CD8 Vbeta repertoire and
      immune function in children with DiGeorge syndrome.
AB  - DiGeorge syndrome (DGS) is a congenital disorder characterized by typical facial
      features, hypoparatyroidism, conotruncal cardiac defects and thymic hypoplasia.
      Although there are some reports addressing lymphocytes counts and function in DGS
      children over time, few data have been reported on the T-cell receptor V beta
      (TCRBV) repertoire in relation to disease progression. The aim of this study was
      to evaluate the degree and nature of immunodeficiency and to investigate a
      possible correlation to clinical findings. We used third complementary region
      (CDR3) size spectratyping as a tool for monitoring T-cell repertoire diversity in
      7 DGS's children. The rate of thymic output, the phenotype and function of
      peripheral T-cells and the humoral immunity were also investigated. At baseline a
      profound alteration of the TCR repertoire was noted, mainly in the CD8+ T-cells,
      in DGS patients when compared to a control group. Furthermore, analysis of thymic
      output showed a significant decrease in TCR rearrangement excision circles
      (TRECs) levels in the patient group. Immunoglobulin abnormalities were also
      detected. The observed TCR repertoire alterations, although not statistically
      significant, may suggest an increased susceptibility to infections. A parallel
      increase in the TCR repertoire diversity and clinical improvement occurred during
      the follow-up. Our results confirm that the extent of immunodeficiency is highly
      variable and could improve through childhood, and indicate that TCR repertoire
      may be a useful marker to clinically monitor thymic function in this primary
      immunodeficiency.

PMID- 15981091
TI  - Axon reactive B cells clonally expanded in the cerebrospinal fluid of patients
      with multiple sclerosis.
AB  - Demyelination and axonal loss have been described as the histological hallmarks
      of inflammatory lesions of multiple sclerosis (MS) and are the pathological
      correlates of persistent disability. However, the immune mechanisms underlying
      axonal damage in MS remain unknown. Here, we report the use of single chain
      variable domain fragments (scFv) from clonally expanded cerebrospinal fluid (CSF)
      B cells to show the role of an anti-axon immune response in the central nervous
      system (CNS) in MS. The cellular and subcellular distribution of the antigen(s)
      recognized by these CSF-derived clonal scFv antibodies (CSFC-scFv Abs) was
      studied by immunochemical staining of brain tissues obtained at autopsy from
      patients with MS. Immunochemistry showed specific binding of CSFC-scFv Abs to
      axons in acute MS lesions. The stained axons showed three major types of axonal
      pathological changes: 1) linear axons, axonal ovoid formation, and axonal
      transection were seen in the myelinated white matter adjacent to the lesion; 2)
      accumulation of axonal ovoid formations and Wallerian degeneration were seen at
      the border between demyelinated lesions and the adjacent white matter; and 3)
      Wallerian degeneration occurred at the center and edge of acute demyelinated
      lesions. These findings suggest a B cell axonal specific immune response in the
      CNS in MS.

PMID- 15981093
TI  - Vitamin a deficiency in patients with common variable immunodeficiency.
AB  - Vitamin A, a naturally occuring antioxidant micronutrient, has immunomodulating
      effect in patients with immunodeficiency, including an influence on cytokine
      production and lymphocyte growth and functions. Vitamin A deficiency is
      associated with a shift from type 2 cytokines to predominantly type 1 cytokines.
      The aims of this study were to determine Vitamin A status in Common variable
      immunodeficiency (CVID) patients and the relationship between Vitamin A status
      and cytokines production. Serum Vitamin A, neopterin, TNF-alpha, IL-2, IL-4, and
      IL-10 levels were determined in 19 CVID patients and 15 healthy children. Effects
      of 9-cis retinal, Vitamin A derivative, on cytokines (TNF-alpha, IL-2, IL-4 and
      IL-10) production in lymphocytes were tested in vitro condition using lymphocyte
      cultures obtained from CVID patients and healthy children.Serum Vitamin A level
      in CVDI patients was, 21.1+/- 1.5 microg/dL, significantly (p < 0.001) lower than
      the value, 35.7+/- 1.8 microg/dL, observed in healthy children. Serum neopterin
      level in the patients was, 9.8+/- 2.9 nmol/L, higher (p < 0.05) than the value,
      3.9+/- 0.7 nmol/L, observed in control group. Common variable immunodeficiency
      patients, serum IL-4 level was significantly (p < 0.05) lower than the value
      observed for healthy children. Serum TNF-alpha, IL-2 and IL-10 levels were
      similar in the patients and healthy children. Vitamin A derivative, 9-cis
      retinal, increased TNF-alpha and IL-4 production in cultured mononuclear cells
      obtained from control and CVID patients. Vitamin A derivative, also, increased IL
      2 and Il-4 production in cultured mononuclear cells obtained from CVID patients.
      These results show that CVID patients have low serum Vitamin A levels and high
      serum neopterin levels. A supplementation with Vitamin A may have role in
      downregulation of inflammatory responses in CVID patients.

PMID- 15981094
TI  - Characterization of anti-mesangial cell antibodies and their target antigens in
      patients with lupus nephritis.
AB  - The pathogenetic mechanisms of lupus nephritis (LN) remain to be elucidated. In
      our previous study, autoantibodies against human glomerular mesangial cells (HMC)
      were identified in sera of most patients with lupus nephritis. The current study
      is to investigate the binding characteristics of anti-mesangial cell antibodies
      to human mesangial cell membrane. Serum samples were collected from 54 patients
      with renal biopsy proven lupus nephritis, 12 patients with systemic lupus
      erythematosus without clinical renal involvement, and 15 healthy subjects.
      Membrane proteins were obtained from in vitro cultured HMC by sonication and
      sequential centrifugation. DNase I were employed to remove DNA fragments in sera
      and membrane protein preperation and IgG F(ab')2 was obtained by pepsin
      digestion. Western Blot analysis was used to characterize the antibody and
      antigen interaction. In results, 25 of 54 (46.3%) sera from patients with lupus
      nephritis had anti-mesangial cell antibodies targeted at 74 kDa, 63 kDa, 52 kDa
      and 42 kDa protein bands of HMC membrane. Only four of 12 (33.3%) sera from
      patients without renal involovement recognized the protein bands at 74 kDa and 63
      kDa, but not 52 kDa and 42 kDa. DNase treatment of the HMC membrane and the sera
      did not affect the binding. IgG F(ab')2 from sera of 10 patients with positive
      anti-mesangial cell antibodies could still bind the 63 kDa protein. In
      conclusion, anti-mesangial cell antibodies from sera of patients with lupus
      nephritis could bind membrane proteins of HMC directly without a DNA bridge and
      the binding was through antigen-antibody interation. Anti-mesangial cell
      antibodies might play some role in the pathogenesis of lupus nephritis(LN).

PMID- 15981095
TI  - Spontaneous proliferation and type 2 cytokine secretion by CD4+T cells in
      patients with metastatic melanoma vaccinated with antigen-pulsed dendritic cells.
AB  - We observed the induction of spontaneous, i.e., without adding exogenous antigen,
      in vitro proliferation of PBMCs from patients with stage IV melanoma who
      underwent repeated vaccinations with antigen-loaded dendritic cells (DCs) derived
      from CD34(+) hematopoietic progenitors (CD34-DCs). Proliferating cells are
      CD4(+)T cells. Their proliferation is dependent on (1) CD11c(+) myeloid DCs,
      since their depletion from PBMCs abolishes it; and (2) IL-2, as it can be blocked
      by neutralizing anti-IL-2 antibodies. Spontaneous proliferation is associated to
      the secretion of type 2 cytokines. To analyze the frequency of spontaneous
      proliferation induction in the cohort of 18 vaccinated patients, an index of
      spontaneous proliferation was defined as a ratio of PBMCs proliferation from post
      vs pre-DC vaccination blood samples. Ten out of sixteen analyzed patients showed
      an index > 2. The index of spontaneous proliferation correlates with antigen
      specific PBMC proliferation to the vaccine antigen KLH. Furthermore, both
      spontaneous- and antigen-specific proliferation in PBMC cultures are dependent on
      blood myeloid DCs.

PMID- 15981096
TI  - Effect of hepatitis C virus coinfection on humoral immune alterations in naive
      HIV-infected adults on HAART: a three year follow-up study.
AB  - Whether HAART allows complete recovery of humoral immune function in HIV-infected
      individuals is still controversial. Our objective was to study the effect of
      HAART on both B cell repopulation and hypergammaglobulinemia in 72 naive
      patients, including 35 HCV-coinfected individuals, during 156 weeks on HAART. The
      possible role of HCV coinfection on the recovery of the humoral immune system was
      also investigated. At baseline, HCV-coinfected patients had greater circulant IgG
      levels than HIV-only-infected patients, while B cell count and CD21(low) B cell
      subpopulation were similar in both groups. During HAART, HIV-only-infected
      patients reached normal B cell counts and circulant IgG levels, while HCV
      coinfected individuals did not. CD21(low) B cell subpopulation significantly
      decreased in both groups of patients at week 48 after the initiation of HAART
      compared to baseline. Thus, B cells remained continuously stimulated in HCV
      coinfected patients and this stimulation seemed to be through a CD21-independent
      pathway.

PMID- 15981097
TI  - Apoptosis and proliferation: correlation with p53 in astrocytic tumours.
AB  - Apoptosis and cell proliferation occur simultaneously in tumour tissue with
      tumour suppressor gene, p53 being one of the key players in the complex
      relationship between these two key phenomena. We, as well as several other
      groups, have earlier demonstrated the association of p53 immunopositivity with
      increased degree of cell proliferation in astrocytic tumours. Here we have
      studied the extent of apoptosis in 62 primary human astrocytic tumours [25
      Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28 Glioblastoma
      multiforme (GBM)] in relation to tumour grade, proliferative status and p53
      protein expression. Apoptosis was measured by the TUNEL assay while, cell
      proliferation (MIB-1 index) and p53 protein immunoreactivity were evaluated by
      immunohistochemical staining using MIB-1 and DO-1 monoclonal antibodies
      respectively. The apoptotic index (AI) was greater in GBM than in AA or DA, and
      more in tumours with p53 immunopositivity than in those without. The most
      striking observation was the strong correlation between Apoptotic index (AI) and
      proliferation index (PI) in p53 negative GBM (r=0.766, P < 0.005). However this
      was not observed in p53 +ve GBM or in low grade DA either p53 positive or
      negative. Taking p53 negativity in IHC as evidence of a functional gene/protein,
      this extends the link between proliferation and apoptosis, hitherto observed only
      in cultured cells with functional p53, to a subset of solid tumours.

PMID- 15981098
TI  - CIC, a gene involved in cerebellar development and ErbB signaling, is
      significantly expressed in medulloblastomas.
AB  - In children, the majority of brain tumors arise in the cerebellum.
      Medulloblastomas, the most common of these, are believed to originate from the
      granule cell lineage. We have recently identified a mammalian gene, capicua
      (Cic), the ortholog of a Drosophila gene implicated in c-erbB (Egfr) signaling,
      which is predominantly expressed during mouse granule cell development. Its
      expression in medulloblastoma is therefore of particular interest. In the present
      study the expression of human CIC in medulloblastoma was analyzed. In silico SAGE
      analysis demonstrated that medulloblastomas exhibited the highest level of CIC
      expression and expression was most common in tumors of the CNS in general. RT-PCR
      and in situ hybridization verified the expression of CIC in tumor cells, although
      the level of expression varied between different medulloblastoma subtypes. The
      expression of CIC did not correlate with other markers, such as neurofilament,
      GFAP and Mib-1. In postnatally developing cerebellum, in silico analysis and in
      situ hybridization both indicated a strong correlation between Cic expression and
      the maturation profile of cerebellar granule cell precursors. Expression of CIC
      is therefore a feature shared between immature granule cells and the tumors
      derived from them. Cic has been implicated as a mediator of ErbB signaling and
      this pathway has been associated with a poor prognosis for medulloblastomas.
      Therefore, further analysis of the role of Cic is likely to provide valuable
      insight into the biology of these tumors. Additionally, study of genes such as
      CIC should provide objective criteria by which, in combination with other markers
      and clinical data, to categorize these tumors into subgroups that might allow
      better allocation into specific treatment regimes.

PMID- 15981099
TI  - Assessment of tumor cell invasion factors in gliomatosis cerebri.
AB  - Gliomatosis cerebri (GC) is a rare brain tumor characterized by widespread
      infiltration of large parts of the brain and sometimes even the spinal cord. To
      determine the cause of this extraordinary degree of brain invasion, we studied
      immunoexpression of factors associated with brain infiltration in low-grade and
      high-grade tumor samples from nine GC cases. We further determined the allelic
      status of the fibroblastic growth factor receptor 4 (FGFR4) gene at position 388
      (arginine [Arg(388)] or glycine [Gly(388)]) in eighteen GC patients, because the
      presence of at least one Arg(388) allele has been suggested to favor tumor cell
      motility compared to tumor cells homozygeous for the Gly(388) allele.
      Immunohistochemical analyses showed that tumor samples from three GC cases
      expressed Tenascin-C, whereas six cases had CD44 - immunopositive tumor samples.
      Expression of MMP-9 was not observed in any of the nine GC patients. FGFR4
      genotyping revealed the presence of the Arg(388) in 72% of the eighteen GC cases,
      a frequency similar to the one found in 21 common astrocytomas (71%). In tumor
      free control DNA, the Arg(388) phenotype was present in 60%. These data indicate
      that CD44 expression might be related to the tumor infiltration in GC, and that
      patients suffering from GC or other common astrocytomas do not have a
      significantly increased frequency of the tumor cell motility-favoring Arg(388)
      FGFR4 allele.

PMID- 15981100
TI  - Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1
      gene inactivation.
AB  - OBJECT: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate
      through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream
      molecular mechanism remains unclear. We histologically and molecularly reviewed
      our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of
      cyclin D1, a potential molecular target of hSNF5/INI1. METHODS: We analyzed 16
      tumors under three years of age: seven medulloblastomas, three anaplastic
      ependymomas (E IIIs), two each of supratentorial primitive neuroectodermal tumors
      (sPNETs) and choroid plexus carcinomas (CPCs), and one each of neuroblastoma and
      pineoblastoma. Immunohistochemistry for glial fibrillary acidic protein,
      vimentin, epithelial membrane antigen, smooth muscle actin and cyclin D1 was
      performed. Polymerase chain reaction (PCR)-single-strand conformation
      polymorphism analysis with direct sequencing, differential PCR and microsatellite
      analysis were conducted for hSNF5/INI1mutation, homozygous deletion and loss of
      heterozygosity (LOH) on 22q, respectively. Because of the presence of rhabdoid
      cells and the polyimmunophenotypic features, the diagnosis was revised to AT/RT
      in five (31%) tumors, namely, two E IIIs and one each of medulloblastoma, CPC and
      pineoblastoma. Three of them harbored such hSNF5/INI1 aberrations as germline
      single base deletion (492/6 delC) and missense mutation (C157T) together with LOH
      22q or homozygous deletion. Cyclin D1 was overexpressed in those three tumors but
      not in the two that lacked hSNF5/INI1 inactivation. CONCLUSION: AT/RT can be
      misdiagnosed as a variety of tumors, including ependymoma that potentially
      harbors LOH 22q. Our data indicate that cyclin D1 is a target of hSNF5/INI1in
      primary tumors.

PMID- 15981101
TI  - Absence of histological signs of tumor progression in recurrences of completely
      resected meningiomas.
AB  - In meningioma recurrences a tumor progression has been proposed on a molecular
      genetic basis. From the histological point of view the problem has not been
      sufficiently investigated. Recurrences mainly depend on tumor location,
      histology, resection type and on the tumor growth in the adjacent nervous tissue.
      Seventy-six completely resected recurrent meningiomas have been studied. Most
      tumors were convexity or parasagittal meningiomas. The number of recurrences
      studied per tumor varied from 1 to 5. Besides histological methods,
      immunohistochemistry for Ki-67 MIB-1, TUNEL for apoptosis, counts of mitoses and
      molecular genetics for CDKN2A were performed. No variation of the mitotic index
      (MI) or MIB-1 labeling index (LI) was observed in recurrences. Histological
      features, the number of mitoses and the MIB-1 LI showed a great regional
      variability. Loss of heterozygosity (LOH) of CDKN2A was found to be slightly more
      frequent in the first recurrence than in the initial tumor, but it was lower in
      the following recurrences. The nervous tissue adjacent to the tumor could contain
      meningothelial cells and be responsible for recurrences. The number of mitoses
      appeared to be the most important criterion for establishing the tumor grade. The
      histological aspect does not change in recurrences and there is no progression.
      The greater number of recurrences in atypical and anaplastic tumors depends on
      their initial higher proliferation capacity. The occurrence of tumor
      meningothelial cells in the adjacent nervous tissue or in the thickened
      arachnoidal membrane can be responsible for recurrence.

PMID- 15981102
TI  - Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with
      abnormal accumulation of CTNNB1.
AB  - We analyzed mutation of the APC, AXIN1, and GSK3genes in 14 pituitary adenomas
      with abnormal nuclear accumulations of CTNNB1. These tumors did not harbor
      mutation of the CTNNB1 gene. The genes analyzed encode proteins associated with
      ubiquitin-mediated degradation of CTNNB1. Although the regions encoding
      functional domains of these protein products were analyzed, no significant
      genetic alterations were found. Furthermore, the antibody for the C-terminus of
      APC detected normal expression of the APC protein in these pituitary adenomas.
      Our present results imply that an unknown mechanism(s) accelerates the
      accumulation of CTNNB1 that plays an important role in the pathogenesis of human
      pituitary adenomas. However, the possibility that mutation of regions outside of
      our survey or epigenetic mechanism play an important role cannot be excluded.

PMID- 15981103
TI  - Images in neuro-oncology.

PMID- 15981104
TI  - Utility of three-dimensional anisotropy contrast magnetic resonance axonography
      for determining condition of the pyramidal tract in glioblastoma patients with
      hemiparesis.
AB  - BACKGROUND AND PURPOSE: Three-dimensional anisotropy contrast magnetic resonance
      axonography (3DAC) is a technique for diffusion weighted magnetic resonance
      imaging (DWI) that offers reliable visualization of the pyramidal tracts. This
      study evaluated condition of the pyramidal tract using 3DAC in glioblastoma
      patients with hemiparesis. METHODS: In 18 glioblastoma patients before surgery,
      3DAC findings of the pyramidal tract responsible for hemiparesis were compared
      with finding from proton density-weighted imaging (PDWI). To estimate extent of
      pyramidal tract destruction, fractional anisotropy (FA) values using diffusion
      tensor magnetic resonance imaging were examined for both the responsible and non
      pathological pyramidal tracts. RESULTS: In all five patients for whom PDWI
      indicated no hyperintense foci in the responsible pyramidal tract, 3DAC
      demonstrated no change in color. When PDWI revealed hyperintense foci, 3DAC
      showed two types of findings: no color change (five patients); or obscured dark
      area (six patients). When 3DAC showed a dark area, mean FA value in the
      responsible tract was significantly lower than that for the non-pathological
      tract. CONCLUSION: When PDWI indicates hyperintense foci on the pyramidal tract,
      3DAC allows prediction of pyramidal tract condition, such as large tumor
      invasion.

PMID- 15981105
TI  - Advances in surgical management of malignancies of the cranial base: the extended
      transbasal approach.
AB  - The extended transbasal approach combines a bifrontal craniotomy with an orbital
      nasal and potentially a sphenoethmoidal osteotomy to provide excellent access to
      malignancies of the anterior, middle and posterior skull base. The approach
      enables the en bloc resection of tumors within the frontal lobes, orbits,
      paranasal sinuses and sphenoclival corridors without brain retraction and may
      obviate the need for transfacial access. We present our 7-year experience during
      which 29 patients underwent surgery with the extended transbasal exposure. In 25
      patients the extended transbasal approach was used alone; in the remaining four
      it was combined with additional approaches. With exception of two patients, all
      lesions were removed en bloc. Reconstruction was accomplished with the use of
      pericranium and in some instances a temporalis muscle pedicle or a gracilis
      microvascular free flap. There were no mortalities associated with this approach.
      Seven patients experienced infections, four patients experienced cerebral spinal
      fluid (CSF) leakage, two patients who had received adjuvant radiation experienced
      scalp necrosis, three patients experienced pneumocephalus, and 29 patients
      experienced cranial neuropathies, the majority of which were loss of olfaction.
      The average follow-up for our patients was 34 months with a range of 2--62
      months.

PMID- 15981106
TI  - Predictors for patterns of brain relapse and overall survival in patients with
      non-small cell lung cancer.
AB  - Our goal was to investigate prognostic factors for different patterns of brain
      relapse and overall survival so that treatments could be tailored and treatment
      outcomes improved. We studied 292 patients with non-small cell lung cancer
      (NSCLC) who had symptomatic, solitary, or multiple brain metastases (isolated or
      not isolated from extracranial metastases) that had developed early (<or=6
      months) or late (>6 months) from initial diagnosis. Factors affecting patterns of
      relapse and survival were analyzed by univariate and multivariate analyses. Good
      ECOG performance status (PS) at the time of NSCLC diagnosis was the most
      important factor that predicted late (rather than early) relapse and improved
      survival, and was the only factor that predicted isolated brain metastases.
      Patients whose lungs showed a complete response (CR) to treatment had a higher
      rate of late brain relapses than non-responders (NR) did (67.3% vs. 7.8%,
      P<0.001). CR patients also experienced a longer median overall survival than NR
      patients. Patients with late brain relapses showed better median survival times
      (18 months vs. 4 months, P<0.0001) than patients with early relapses, and this
      was an independent factor by Cox regression analysis. Our findings provide a
      justification for enrolling patients with good PS and controlled lung lesions
      into clinical trials for the prevention of early, non-isolated brain relapse.
      More aggressive therapeutic approaches should be applied to patients with late,
      isolated and solitary relapses to improve both quality and quantity of life.

PMID- 15981107
TI  - Surgical treatment of intramedullary spinal cord metastases of systemic cancer:
      functional outcome and prognosis.
AB  - OBJECTIVE: Intramedullary spinal cord metastases (ISCM) of systemic cancer are
      rare. To date, patients with ISCM tend to benefit only to a limited extend from
      surgery and adjuvant therapy. Subject of this investigation is to assess
      predictive factors for surgical outcome and survival and to evaluate the value of
      surgical radicality in the treatment of ISCM. PATIENTS AND METHODS: Between 1990
      and 2004, a series of 146 patients with intramedullary tumors underwent surgical
      treatment in our institution. Among these, 13 patients with intramedullary cancer
      metastases (7 adenocarcinomas, 3 poorly differentiated carcinomas, 3 sarcomas)
      were identified. Standard microsurgical removal of the ISCM was performed.
      Functional outcome was graded according to a standardized scale and factors
      influencing outcome and survival were statistically analyzed. RESULTS: Median
      progression-free survival was 13 weeks and median overall survival was 31 weeks.
      In 5 patients (38) the intramedullary lesion was the initial manifestation of the
      malignant disease. All poorly differentiated carcinomas and all sarcomas were
      resected incompletely. Surgical radicality presented a negative predictive factor
      for functional outcome, increasing radicality leading to functional
      deterioration. Age, sex, tumor localization, surgical radicality and the presence
      of neoplastic meningeosis did not affect survival. CONCLUSION: Surgery of ISCM
      can be performed with an acceptable operative morbidity. Radicality depended on
      tumor histology. However, radical tumor removal did not affect survival and was
      correlated with a poor functional outcome. Therefore, complete surgical removal
      of ISCM should only be intended in patients in whom an unproblematic excision is
      feasible.

PMID- 15981108
TI  - Primary meningeal pheochromocytoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial pheochromocytomas are extremely rare
      tumors. Reported cases include metastatic tumors without known cases of primary
      pheochromocytomas. CLINICAL PRESENTATION: A female patient with a history of a
      surgically treated adrenal pheochromocytoma presented 23 years later with
      headache, nausea and blood hypertension. A head CT scan demonstrated a right
      temporoparietal meningeal heterogeneous lesion with a surrounding hyperdense
      ring. No other lesions were disclosed. INTERVENTION: The lesion developed in the
      inner and outer surface of the dura without brain infiltration and it was totally
      resected. The patient is free of disease 6 years after brain surgery. CONCLUSION:
      To our knowledge this is the first reported case of a primary meningeal
      pheochromocytoma.

PMID- 15981109
TI  - Frame-based stereotactic biopsy remains an important diagnostic tool with
      distinct advantages over frameless stereotactic biopsy.
AB  - OBJECT: As the availability of image-guided surgical navigation systems has
      increased, the application of frame-based biopsy has declined at our institution,
      despite equivalent accuracy and safety. There are several cost issues separating
      the use of surgical navigation systems and stereotactic frames for simple biopsy
      which may have implications in this era of health care cost control. We
      retrospectively reviewed the UCSF experience with stereotactic brain biopsy from
      a 9 year period. METHODS: Data were collected for 213 consecutive stereotactic
      brain biopsies performed at UCSF (139 frame-based and 74 frameless). There were
      no significant differences between the frame-based and frameless biopsy groups
      with regard to patient demographics, overall histopathology, proportion of
      nondiagnostic biopsies, or incidence of complications. General anesthesia was
      used for 9 (6%) and 70 (95%) of the frame-based and frameless biopsy cases,
      respectively. Frame-based biopsies required a mean of 114+/-3 min of operating
      room time, while frameless biopsies required 185+/-6 min (P<0.0001). For patients
      admitted to our neurosurgery service who underwent frame-based (n=110) or
      frameless (n=52) biopsy within 24 h of admission, the mean lengths of hospital
      stay were 1.8+/-0.2 and 3.2+/-0.6 days, respectively (P=0.007). CONCLUSION: Frame
      based and frameless stereotactic biopsy approaches were equally effective at
      providing a tissue diagnosis with minimum morbidity and mortality. The frame
      based approach, however, required significantly less anesthesia resources, less
      operating room time and shorter hospital stays, and thus should still be
      considered a first-line approach for stereotactic brain biopsy.

PMID- 15981110
TI  - Case report: cavernous sinus metastasis of the parotid carcinoma: a very unusual
      case.
AB  - Cavernous sinus is an uncommon site of metastasis for the head and neck tumors,
      and especially for the tumors of parotid gland. The case reported here is the
      second reported case of parotid carcinoma metastatic to the cavernous sinus,
      proven by histopathology. Also it is the first reported parotid gland acinic cell
      carcinoma metastasis to the cavernous sinus.

PMID- 15981111
TI  - Maintenance of fertility following treatment with temozolomide for a high grade
      astrocytoma.

PMID- 15981113
TI  - Safety and efficacy of eversion carotid endarterectomy for the treatment of
      recurrent stenosis: 20-year experience.
AB  - Current options for treating recurrent carotid stenosis (RCS) include standard
      longitudinal arteriotomy and patch angioplasty with or without carotid
      endarterectomy (s-PCEA), carotid-carotid bypass, or carotid angioplasty and stent
      (CAS). Eversion carotid endarterectomy (e-CEA) is an effective procedure for
      treating primary carotid stenosis, yet it has not been reported for treating RCS.
      We evaluated the feasibility and outcome of e-CEA for treating of RCS in
      comparison to s-PCEA. The records of all patients undergoing elective CEA for
      symptomatic and asymptomatic high-grade RCS from January 1981 to July 2002 were
      reviewed. Although during the earlier period s-PCEA was performed preferentially,
      this paradigm changed to e-CEA being the preferred technique for treatment of
      RCS. During the course of postoperative follow-up when duplex sonography
      suggested high-grade RCS, the diagnosis was confirmed via arteriography. Data on
      cranial nerve injury, recurrent stenosis, stroke, and death were prospectively
      collected into a vascular registry database and analyzed retrospectively,
      Students' t-test and chi-square analysis were used to compare the group's
      baseline characteristics and outcomes. Over a 21-year period, 7001 patients
      underwent primary CEA for symptomatic (n = 2405, 34%) or asymptomatic (n = 4596,
      66%) high-grade stenosis via standard (n = 1501, 21%) or eversion (n = 5500, 79%)
      techniques. Fifteen (25%) patients had 70 to 80% stenosis, 30 (51%) had 81 to 90%
      stenosis, and 14 (24%) had 91 to 99% stenosis. During this time period, 59
      patients presented with symptomatic (n = 18, 31%) or asymptomatic (n = 41, 69%)
      high-grade RCS and underwent operative repair via s-PCEA (n = 22, 37%) or
      eversion (n = 37, 63%) techniques. The mean time interval for repeat carotid
      surgery for RCS was 49 months in the s-PCEA group and 48 months in the e-CEA
      group. Permanent cranial nerve injuries, stroke, and recurrent restenosis
      occurred in one (4.5%), one (4.5%), and one (4.5%) of the patients undergoing s
      PCEA, respectively. In the e-CEA group, these events occurred in one (27%), none
      (0%), and one (2.7%) patients, respectively, There were no deaths during the 30
      day postoperative period. Eversion CEA is a feasible option for the treatment of
      many RCSs and can be performed safely with a low rate of cranial nerve injury,
      recurrent stenosis, stroke, and death.

PMID- 15981114
TI  - Managing anomalous splenic artery aneurysm: a review of the literature and report
      of two cases.
AB  - The splenic artery originates from the superior mesenteric artery in
      approximately 1% of cases, which may explain the extreme rarity of aneurysms
      involving this anomalous branch, with only five cases reported in the
      international literature to date. We report our experience of managing two
      patients with aneurysms involving splenic arteries arising from the superior
      mesenteric artery, one treated surgically and the other percutaneously. From a
      diagnostic point of view, the first approach is ultrasound, while computed
      tomographic (CT) scan and angiography enable a better definition of the lesion
      and of the anatomical anomaly; CT angiography is currently the method of choice
      for the preoperative workup. Finding these two anomalies in association is so
      rare that it is impossible to draw any final conclusions as to the best type of
      treatment. In the authors' experience, both surgery and percutaneous treatment
      can prove useful.

PMID- 15981115
TI  - Pancreaticoduodenal artery aneurysms associated with celiac axis occlusion.
AB  - True aneurysms of the pancreaticoduodenal artery associated with celiac axis
      occlusion are very rare; only 38 cases have been reported, according to our
      literature review. We present three consecutive cases with different options of
      surgical treatment.

PMID- 15981116
TI  - Endovascular stent graft treatment of a traumatic aortocaval fistula.
AB  - Aortocaval fistula (ACF) is an infrequently reported sequela of trauma. Most ACF
      have been repaired via an open approach. During the past 10 years, there has been
      one reported case of spontaneous ACF and two cases of traumatic ACF repaired
      using an endovascular technique. We present a third case of traumatic ACF
      repaired with an endovascular stent graft. A 40-year-old male sustained two
      gunshot wounds to the right chest and one to the right upper abdomen. He was
      taken from the emergency department directly to the operating room, where an
      exploratory laparotomy was performed. Through-and-through injuries to the stomach
      and transverse colon were repaired primarily. Subsequently, the patient developed
      abdominal compartment syndrome. An urgent exploratory laparotomy was performed,
      revealing a nonbleeding hematoma on the posterior lateral surface of the right
      lobe of the liver, which was left undisturbed. Open abdominal management was
      instituted with vacuum pack closure. On the nineteenth hospital day, the patient
      again had a significant decrease in hematocrit. An aortogram was performed in
      order to evaluate the patient for intrahepatic arterial bleeding amenable to
      transcatheter embolization. There was no evidence of hepatic arterial bleeding.
      However, a supraceliac ACF was identified. The patient was taken to the operating
      room, and an AneuRx aortic extension cuff was advanced under fluoroscopy and
      deployed to cover the fistula. Completion angiography revealed total obliteration
      of the ACF and appropriate placement of the stent graft. Postoperatively, the
      patient was returned to the intensive care unit, where his hospital course was
      complicated by ventilator-associated pneumonia and sepsis. Repeat computed
      tomographic scanning 6 months and 1 year following this repair demonstrated
      patency of the graft without evidence of graft migration or aortocaval
      communication. Further research and experience are necessary with this technique
      regarding long-term outcome and technical aspects. In particular, the sizing
      problems associated with repair of acute traumatic ACF in emergency situations
      should be addressed. The endovascular approach provides an attractive and
      exciting alternative to traditional methods for repair of ACF.

PMID- 15981117
TI  - Successful coaxial double-vein graft for infrarenal aortic pseudoaneurysm due to
      Salmonella infection associated with hepatic resection for hepatocarcinoma.
AB  - This is a case of aortic pseudoaneurysm due to Salmonella aortitis successfully
      treated by coaxial double-vein graft replacement (femoral vein and internal
      jugular vein) associated with hepatic resection for hepatocarcinoma. The aim of
      the technique is to improve the solidness of the vascular anastomosis and the
      tensile strength of the autologous vein graft, thus preventing long-term
      degeneration. Simultaneous hepatic resection did not affect clinical outcome. At
      5-year follow-up, neither morphological alteration of the double-vein graft nor
      neoplastic relapse of the hepatocellular carcinoma was observed. This surgical
      technique could potentially improve long-term outcome and could therefore be
      considered a useful modification of the classic femoral vein graft for
      substitution of the septic infrarenal aorta when an extension to the iliac or
      femoral artery is not necessary.

PMID- 15981118
TI  - Celiac artery compression syndrome due to acute type B aortic dissection.
AB  - Acute distal aortic dissection sometimes causes one or more visceral vessels to
      be stenosed by the thrombosed false lumen. Although stenosis of the only celiac
      artery (CA) usually does not cause ischemic symptoms because of the extensive
      collateral pathways of the mesenteric circulation, we experienced a rare case of
      CA compression syndrome which was caused by acute type B aortic dissection. The
      principal symptom was severe epigastric pain that was refractory to medicinal
      treatment. The angiogram showed absence of the anatomically well-developed
      collateral pathways between the CA and the superior mesenteric artery. We treated
      the patient with percutaneous transluminal angioplasty in the CA. This report
      indicates that attention should be given to the possibility of CA compression
      syndrome in the case of acute distal aortic dissection and that endovascular
      management can be successfully applied to control symptoms caused by the
      syndrome, which is otherwise extremely difficult to repair directly by surgery.

PMID- 15981119
TI  - Gelatinases [matrix metalloproteinase-2 (MMP-2) and MMP-9] induce carotid plaque
      instability but their systemic levels are not predictive of local events.
AB  - Matrix metalloproteinases (MMPs) appear to play a central role in atherosclerotic
      plaque remodeling; however, the relationship of increased MMP levels in inducing
      carotid plaque instability remains controversial. We investigated whether
      gelatinases (MMP-2 and MMP-9) are implicated in carotid intraplaque hemorrhage
      and whether their serum levels may predict local carotid events. Nineteen carotid
      specimens obtained by endarterectomy of 18 patients were studied. The presence of
      gross intraplaque hemorrhage was recorded before plaque removal and
      quantification of MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP
      1) in extracts from (1) the more stenotic area of the plaque, (2) the periphery
      of the plaque, and (3) serum was performed by enzyme-linked immunosorbent assay.
      MMP-9 levels measured in extracts from the most stenotic area were significantly
      higher in patients with intraplaque hemorrhage (p = 0.007); however, serum levels
      showed no difference, while those taken from the periphery of the lesion were
      also increased but did not reach a statistically significant level (p = 0.06). An
      increase in MMP-2 values was observed in the periphery of the lesion (p = 0.04)
      in patients with intraplaque hemorrhage. TIMP-1 levels showed no difference
      between the two groups regardless of the presence or absence of intraplaque
      hemorrhage. No significant differences in MMP levels were observed between
      symptomatic and asymptomatic patients. Increased levels of MMPs, particularly MMP
      9, have been implicated in carotid intraplaque hemorrhage without their serum
      levels being predictive of local events.

PMID- 15981120
TI  - Correlations of cerebrospinal fluid pressure with hemodynamic parameters during
      thoracoabdominal aortic aneurysm repair.
AB  - Central venous pressure (CVP) has long been thought to correlate with
      cerebrospinal fluid (CSF) pressure during thoracoabdominal aortic aneurysm
      repair. We examined hemodynamic factors during thoracoabdominal aortic aneurysm
      surgery to determine their relationship with CSF pressure and aortic cross
      clamping. Hemodynamic parameters and CSF pressure were measured in 124 patients
      at six different stages during repair of descending thoracic or thoracoabdominal
      aortic aneurysms: skin incision, left lung collapse, pump on, aortic clamp on,
      aortic clamp off, and pump off. Stepwise multiple regression analysis was used
      for statistical analysis. CVP was a weak predictor for CSF pressure at the
      beginning of surgery and when the pump was initiated. At the onset of left lung
      collapse, cardiac output correlated with CSF pressure. There were no predictors
      during aortic cross-clamping. Model r2 values were low, ranging 0.03-0.15. We
      found no hemodynamic predictors of CSF pressure throughout the period of aortic
      cross-clamping during descending thoracic or thoracoabdominal aortic aneurysm
      surgery. Model r2 values were low, indicating generally poor prediction of CSF
      pressure.

PMID- 15981121
TI  - Inhibition of intimal/medial hyperplasia by perindopril in canine vein grafts.
AB  - We used a canine model to assess the efficacy of an angiotensin-converting enzyme
      inhibitor (perindopril) at modulating intimal/medial hyperplasia in vein bypass
      grafts. Fourteen beagle dogs were divided into medicated and control groups and
      underwent bilateral grafting of external jugular veins into the common carotid
      artery. Samples of normal veins were obtained from the control group during vein
      grafting. Vein grafts were harvested 1 week and 4 weeks after surgery in both
      groups. Subsequently, intimal/medial thickness was measured by staining with
      hematoxylin and eosin; antibodies for proliferating cell nuclear antigen were
      employed to determine the degree of cellular proliferation; apoptotic cells were
      detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling method. In the medicated group, the intimal/medial cross-sectional area
      was significantly smaller and increased 8- to 9-fold in comparison to the control
      group, which increased 12- to 20-fold. There was a significantly higher rate of
      cell proliferation in the control group, whereas the medicated group showed a
      significantly higher rate of apoptotic cells. These data support the efficacy of
      perindopril at reducing intimal/medial hyperplasia in arterialized vein grafts
      during a short postoperative period.

PMID- 15981122
TI  - Venous angiomata: treatment with sclerosant foam.
AB  - Venous angiomata, or venous malformations, are often present at birth, although
      they may not be evident until later. They consist of a spongy tangle of veins,
      and these lesions usually vary in size. Treatment of venous angiomata is often
      requested for cosmetic reasons, but painful ulcerations, nerve compression,
      functional disability can command care. This presentation describes management
      using sclerosant foam as the treating agent. During a 30-month period ending
      March 2004, 1,321 patients were investigated for venous disorders at the Vein
      Institute of La Jolla. Fourteen (incidence 1%) were found to have venous
      angiomata (: nine women). The age range was 15-76 years (mean 30.8 +/- 18.6).
      Lesions were classified by the Hamburg system and were primarily venous,
      extratruncular in 12 patients and combined extratruncular and truncular in two
      patients. Eight patients, three males, had manifestations of lower extremity
      Klippel-Trenaunay (syndrome; six had only venous angiomas. Only 10 of the 14
      patients were treated. All patients were studied by Doppler duplex examination.
      Selected lesions were chosen for helical computed tomographic studies. Magnetic
      resonance venography was also used to image the lesions, define the deep
      circulation, note connections with normal circulation, identify vessels for
      therapeutic access, and determine infiltration of the lesion into adjacent soft
      tissue. Foam was produced by the Tessari two syringes one three-way stopcock
      teclinique, with the air to Polidocanol ratio being 4 or 5 to 1. This was used at
      1% or 2% concentration, specific for each patient. The SonoSite 190 plus Duplex
      Doppler was used for ultrasound guidance, whenever deep access was required and
      to monitor progress and effects of treatment. A goal was set for each patient
      before treatment was begun. Ten patients were treated, and four await treatment.
      The mean number of treatments was 3.6 +/- 2.8 (range 1-10). A primary goal of
      pain-free healing was set in patients with nonhealing, painful ulceration or
      symptomatic varicose veins. This was achieved in all treated patients.
      Cosmetically, all of the patients were improved, and symptomatic patients were
      relieved of pain. The single complication was formation of a cutaneous ulcer
      following injection of telangiectasias. Sclerosant foam is a satisfactory tool to
      use in treating venous angiomata including the Klippel-Trenaunay syndrome. Use of
      foam sclerotherapy in this experience has proven the technique to be effective,
      essentially pain-free, and durable in the short term.

PMID- 15981123
TI  - Two-graft repair of very proximal superior mesenteric artery aneurysms: a
      technical note.
AB  - Visceral artery aneurysms are found in only 0.2% of the general population. Among
      these, aneurysms of the superior mesenteric artery (SMA) are very unusual and
      account for only 5.5 % to 8 %. Risk of rupture or embolization is the impetus for
      their definitive treatment and this should be performed in acceptable candidates.
      These aneurysms are typically located distal to the origin of the SMA and this
      situation lends itself to interposition grafting as a means of both aneurysm
      repair and reestablishment of prograde SMA blood flow. However, SMA origin
      aneurysms that arise directly from the abdominal aorta add a degree of complexity
      because the vascular reconstruction must include the diseased visceral aorta as
      well as the SMA. In this article we report successful operative treatment of
      large aneurysms at the origin of the superior mesenteric artery using a two-graft
      technique in two elderly patients.

PMID- 15981124
TI  - Delayed development of a traumatic superior mesenteric arteriovenous fistula
      following multiple gunshot wounds to the abdomen.
AB  - Traumatic visceral arteriovenous fistulae are rare and pose a diagnostic and
      therapeutic challenge. We present the case of a 20-year-old male who sustained
      multiple gunshot wounds to the abdomen, injuring the inferior vena cava,
      duodenum, stomach, and small bowel. The patient was taken emergently to the
      operating room for repair of his injuries, which required primary small bowel
      repair, duodenal repair, and inferior vena cava ligation due to exigent
      hemorrhage. At the initial operation there was a normal pulse in the superior
      mesenteric artery at the base of the small bowel mesentery, with no evidence of
      hematoma or thrill in the small bowel mesentery. The patient was subsequently
      returned to the operating room several times for bowel exploration and abdominal
      wall closure with mesh. Ten days after his initial injury, the patient was noted
      to have an abdominal bruit on physical exam. Arteriography demonstrated a fistula
      between the proximal superior mesenteric artery and vein with significant portal
      hypertension. The patient underwent surgical repair of the superior mesenteric
      artery and vein with closure of the fistula. The patient had no further
      complications and was discharged from the hospital 1 month later, after abdominal
      wall skin grafting, in good condition. The patient remains in good health 12
      months later. Continued vigilance and careful physical examination are important
      in the identification of delayed vascular injuries and allow timely treatment and
      avoidance of untoward long-term sequelae.

PMID- 15981125
TI  - Endovascular treatment of a blunt traumatic abdominal aortic injury with a
      commercially available stent graft.
AB  - Abdominal aortic injuries are rarely encountered in blunt abdominal trauma. The
      traditional treatment of these injuries has been surgical exploration and repair.
      Endografts are commonly used in the repair of abdominal aortic aneurysms. We
      present a case of a blunt abdominal aortic injury treated successfully with a
      commercially available endograft. A 26-year-old male was involved in a rollover
      motor vehicle collision. Evaluation revealed an aortic injury as well as a
      concomitant small bowel injury. No treatment of the aorta was undertaken
      initially; however, on 6-month follow-up, the patient developed bilateral hip and
      buttock claudication. Computed tomography and aortography revealed two areas of
      stenosis with an associated pseudoaneurysm. The patient was treated with three 22
      mm AneuRx (Medtronic, Sunnyvale, CA) aortic extender cuffs. Balloon angioplasty
      of the stenosis was also performed. The patient's symptoms resolved, and he was
      well at 9 months postprocedure. We report the use of aortic extender cuffs to
      treat a blunt abdominal aortic injury. The potential to treat these injuries with
      aortic extender cuffs emergently or electively at any institution represents an
      advance in the management of vascular trauma.

PMID- 15981126
TI  - Endovascular repair of an aortopulmonary fistula via the axillary artery.
AB  - A 62-year-old man presented with several months of progressive hemoptysis. He has
      a history of aortobifemoral bypass and thoracofemoral bypass grafts, which were
      both removed due to infection. Evaluation with multiple imaging modalities
      revealed a descending thoracic aortic pseudoaneurysm around the retained
      Dacrontrade mark graft with bronchiectatic changes and consolidation of the
      adjacent left lower lobe. No evidence of direct arterial communication between
      the aorta and the bronchioles was ever demonstrated, but an aortopulmonary
      fistula was suspected. Endovascular repair with several Excluder aortic cuffs
      stacked in the thoracic aorta was successfully performed via the axillary artery.
      Exclusion of the pseudoaneurysm with no evidence of endoleak was noted on
      computed tomography 2 months postoperatively, at which time the patient reported
      complete resolution of his hemoptysis. To our knowledge, this is the first report
      of endovascular repair of an aortopulmonary fistula via the axillary artery.

PMID- 15981127
TI  - Percutaneous thoracic and abdominal aortic aneurysm repair.

PMID- 15981128
TI  - Vascular dysfunction in ischemia-reperfusion injury.
AB  - Microvascular dysfunction mediates many of the local and systemic consequences of
      ischemic-reperfusion (I/R) injury, with a spectrum of changes specific to
      arterioles, capillaries, and venules. This review discusses the specific changes
      in the endothelium during I/R injury; describes the differential responses of the
      various levels of the vasculature including arterioles, capillaries, and venules;
      and explores mechanisms for remote organ injury. Vascular dysfunction is largely
      a consequence of changes in the endothelial cells themselves, affecting the
      integrity of barrier function, cytokine and adhesion molecule expression, and
      vascular tone. The bioavailability of nitric oxide, an important mediator of
      vasodilation, is profoundly decreased during the reperfusion period, resulting in
      impaired vasodilation of arterioles. Release of inflammatory mediators and
      increased expression of adhesion molecules initiate inflammatory and coagulation
      cascades that culminate in the occlusion of capillaries, known as the "no
      reflow''" phenomenon. In postcapillary venules, the recruitment and
      transmigration of leukocytes further compromise the integrity of the endothelial
      barrier and increase the oxidative burden, resulting in leakage and tissue edema.
      I/R injury can have significant and untoward consequences beyond the affected
      tissue, with such conditions as systemic inflammatory response syndrome. This
      review highlights recent progress in understanding of the varied phenomena of
      vascular dysfunction in I/R injury and some promising advances in the
      understanding and application of ischemic preconditioning and other potential
      therapies.

PMID- 15981129
TI  - Consensus clinical guidelines for the assessment of cognitive and behavioural
      problems in Tuberous Sclerosis.
AB  - Tuberous Sclerosis (TSC) is a genetic disorder characterised by abnormal growths
      in a wide range of organs. In the brain, abnormalities of differentiation,
      proliferation and migration can produce a range of neuropsychiatric features such
      as mental retardation, autism and ADHD. Although these manifestations are not
      diagnostic of the disorder, cognitive and behavioural features are often of
      greatest concern to families yet limited clinical assessment and interventions
      are currently offered. A consensus panel at a TSC Brain/Behaviour workshop
      recommended that the cognitive and behavioural profiles of individuals with TSC
      should be assessed at regular intervals in a planned fashion in accordance with
      the difficulties associated with the disorder. Evaluations should include the use
      of standardised neuropsychological and behavioural tools as appropriate to the
      age and developmental level of the individual assessed. These cognitive and
      behavioural profiles should be incorporated in the overall formulation of the
      needs of the person with TSC to plan educational, social and clinical management
      strategies. Assessments should be documented so that individual longitudinal
      progress can be monitored. The paper outlines the problems associated with TSC,
      the purpose of recommended assessments, developmentally appropriate stages for
      assessment, and identifies specific areas that should be targeted for assessment.

PMID- 15981130
TI  - Conduct disordered adolescents hospitalised 1963-1990. Secular trends in criminal
      activity.
AB  - Secular trends in the criminal activity of conduct disordered adolescents
      admitted as psychiatric in-patients in Norway were examined. A nationwide sample
      of 650 adolescents hospitalised with DSM-IV Conduct Disorder during the years
      1963-1990 was followed up 12-33 years after index hospitalisation by register
      linkage to the National Crime Register. In all, 469 patients, 82% of the males
      and 57% of the females, had a criminal record at follow-up. The study population
      was divided into four consecutive cohorts and gender-specific cohort differences
      in registered criminality were investigated, using survival analysis. There was a
      marked increase and subsequent levelling off in overall registered criminality
      from the first to the most recent cohort of conduct disordered females, in
      contrast to unchanged crime rates in conduct disordered males. Monitoring
      specific types of crime, males' violent crime rates initially increased but
      levelled off in more recent cohorts, whereas female violent crime rates increased
      steadily, with the highest level seen in the most recent cohort. A marked
      increase in drug offences was observed in both genders. Cox regression
      demonstrated numerous strong cohort effects, even when controlling for other
      important factors, including substance use comorbidity. Research into causal
      mechanisms is warranted.

PMID- 15981131
TI  - A comparison of mental health problems in kinship and nonkinship foster care.
AB  - OBJECTIVE: Knowledge of the emotional and behavioural problems of children in
      kinship foster care is scarce. No data on such problems in European countries
      have been published. This study compares child psychiatric problems and placement
      characteristics of children living in kinship and nonkinship foster care.
      METHODS: A total of 214 children in kinship and nonkinship foster care, aged 4
      13, participated in the study. The Child Behavioral Checklist (CBCL) was
      completed by their foster parents and demography and placement information was
      collected. RESULTS: Of the nonkinship group, 51.8 % scored above the borderline
      on the CBCL Total Problem score, as did 35.8% of the kinship group. The kinship
      group had fewer previous placements, were more often fostered within their local
      community and had more contact with their biological parents. Kinship foster
      parents had lower social status, in terms of educational level. Variables
      significantly related to high level of the CBCL Total problems score were male
      gender and location of foster home outside community of birth family. Positive
      outcome was significantly associated with placement within the child's own
      community, which in turn was related to kinship placement. CONCLUSIONS: Placement
      in kinship foster care should be considered as a viable possibility.

PMID- 15981132
TI  - Teacher ratings of mental health among school children in Kinshasa, Democratic
      Republic of Congo.
AB  - AIM: In Africa, little is known about child mental health. This study piloted the
      Strengths and Difficulties Questionnaire (SDQ) in Kinshasa, investigated mental
      health problems and the association between these problems and school
      performance, demographic factors, illness and nutrition. METHODS: An
      epidemiological survey was conducted with 1,187 children, 7-9 years old,
      recruited from randomly selected schools. Mental health problems were assessed
      with the SDQ (a behavioural screening tool) administered to teachers. Stability
      of the factor structure was examined using principal component factor analysis of
      the SDQ items. The reliability was evaluated using measures of internal
      consistency of the SDQ scales. RESULTS: Factor analysis yielded five factors,
      similar to the published SDQ scales. The internal consistency was satisfactory on
      all of the SDQ scales. Using the 90th percentile, the cut-off scores were
      somewhat higher than the published cut-off scores in this younger sample. Poor
      nutrition, low socioeconomic status and illness were found to increase the risk
      for mental health problems and low school performance. CONCLUSION: SDQ may be
      considered useful to describe mental health problems among urban African children
      in Kinshasa. An association between mental health, school performance,
      demographic factors, illness and nutrition was found.

PMID- 15981133
TI  - The development of antisocial behaviour from childhood to adolescence. A
      longitudinal twin study.
AB  - Recent theory proposes that aggressive and nonaggressive antisocial behaviour
      (ASB) represent different pathways toward delinquency. It has also been suggested
      that Aggressive ASB is heritable, whereas nonaggressive ASB is more influenced by
      shared environment. The twin study of child and adolescent development is a
      Swedish population-based study of 1,480 twin pairs. The present study included
      1,226 twin pairs. We used the parental-reported Aggression and Delinquency scales
      from the CBCL measured at age 8-9. Delinquent behaviour was measured through self
      report at age 16-17. We explored how genetic and environmental effects influence
      the relationships between aspects of ASB in childhood and adolescent delinquency
      using structural equations modelling. For girls we found that the relationship
      between Aggressive Behaviour and Self-Reported Delinquency was explained by
      genetic influences. The correlation between Delinquent Behaviour and Self
      Reported Delinquency was due to continuity of genetic influences. For boys, there
      was no significant mediation between Aggressive Behaviour and Self-Reported
      Delinquency, but there were significant shared environmental effects on the
      relationship between Delinquent Behaviour and Self-Reported Delinquency. Our
      results suggest that there are sex differences in the development of ASB. The
      hypothesis that the aggressive pathway is genetically mediated was supported in
      girls, whereas the hypothesis that the nonaggressive pathway is environmentally
      dependent was supported in boys.

PMID- 15981134
TI  - Psychiatric symptoms in low birth weight adolescents, assessed by screening
      questionnaires.
AB  - OBJECTIVE: The aim of this study was to explore psychiatric symptoms in low birth
      weight adolescents, and the usefulness of questionnaires compared with
      psychiatric interview. DESIGN/STUDY GROUPS: A population-based follow-up study of
      56 very low birth weight (VLBW), 60 term small for gestational age (SGA) and 83
      control adolescents at 14 years of age was made. OUTCOME MEASURES: The Achenbach
      System of Empirically Based Assessment (ASEBA) and the Strengths and Difficulties
      Questionnaire (SDQ) were rated by adolescents, parents and teachers. The results
      were compared with diagnostic assessment based on the semi-structured interview,
      Schedule for Affective Disorders and Schizophrenia for School Aged Children (K
      SADS). RESULTS: VLBW adolescents had more psychiatric symptoms than controls,
      especially attention deficit, emotional, behavioural, social and also academic
      problems. Although less consistent, the SGA group had more emotional, conduct and
      attention deficit symptoms than controls. Results remained essentially the same
      when adolescents with low estimated IQ were excluded, and persisted after
      controlling for possible confounders. The sensitivity and specificity of ASEBA
      and SDQ differed between informants and groups. CONCLUSION: VLBW adolescents are
      at risk of developing psychiatric symptoms, and reduced social and academic
      skills by the age of 14. Term SGA adolescents may have discrete emotional,
      behavioural and attention deficit symptoms. ASEBA and SDQ provide a useful
      supplement to psychiatric interview.

PMID- 15981135
TI  - Sleep problems in adolescence. A study of senior high school students in Greece.
AB  - OBJECTIVES: The aim of this study was to evaluate sleep habits and sleep-related
      problems in high school adolescent students in Greece through the Athens Insomnia
      Scale and to assess the relation of these problems to demographic and other
      variables. METHODS: The Athens Insomnia Scale 5-item version (AIS-5) was
      administered to 713 adolescent senior high school students in the Greater Athens
      Area. Data such as age, sex, school records, and time spent per week in school
      related and extracurricular activities were collected. RESULTS: The sample's mean
      sleep duration was 7.5 h, mean bedtime 00.20 a.m. and wake-up time 7.15 a.m.
      Total sleep time was not affected by gender, but was influenced by time spent in
      various activities. Sleep complaints were related to delayed sleep, onset latency
      and insufficient total duration of sleep. Of the respondents, 30% estimated that
      their sleep onset latency was markedly delayed and 30% reported that their total
      sleep time was markedly insufficient. Girls complained more than boys, while
      correlations showed that students with lower academic performance and those in
      second grade were more likely to have higher AIS-5 scores. CONCLUSIONS: The
      results show that the sleep time of high school students is dependent on
      practical matters such as school schedule and other activities, while sleep
      complaints are related to female gender, bad school performance as well as to the
      second grade. The difference between actual sleep time and sleep complaints
      should be considered when studying the sleep of adolescents.

PMID- 15981136
TI  - The adolescent outcome of hyperactive girls. Self-reported interpersonal
      relationships and coping mechanisms.
AB  - The aim of the study was to clarify the developmental risk for interpersonal
      relationship problems and ineffective coping strategies associated with
      hyperactive behaviour in girls in a longitudinal epidemiological design. This was
      investigated in a follow-up study of girls who were identified by parent and
      teacher ratings in a large community survey of 6- and 7-year-olds as showing
      pervasive hyperactivity or conduct problems or the comorbid mixture of both
      problems or neither problem. They were later investigated, at the age of 14-16
      years, in a detailed interview. Childhood hyperactivity was a risk for disrupted
      relationships in adolescence with peers and the opposite sex, but not parents.
      Findings were independent of the existence of conduct problems. Hyperactivity was
      a risk for the use of a wide variety of ineffective coping strategies. On the
      other hand, conduct problem girls reported applying specific coping strategies,
      but rated these to be ineffective. It is concluded that early therapeutic
      interventions targeting the development of social skills and problem-solving
      skills are required in order to help overcome these problems in later life.

PMID- 15981137
TI  - Alcohol abuse in Russian delinquent adolescents. Associations with comorbid
      psychopathology, personality and parenting.
AB  - INTRODUCTION: Adolescent delinquency and alcohol abuse have become a growing
      concern in Russia. Psychopathology, a dysfunctional family and specific
      personality factors have all been linked to addictive and antisocial behavior.
      Since delinquent youth represent a specific risk group, where alcohol misuse
      tends to be more pronounced than in the general population, the objectives of
      this study were: 1) to compare differences in personality and parenting factors,
      and in psychopathology in juvenile delinquents with and without alcohol abuse;
      and 2) to evaluate the associations between alcohol abuse, personality and
      parenting factors, after controlling for comorbid psychopathology. METHODS:
      Psychopathology, including alcohol abuse, was assessed by means of a psychiatric
      interview in 229 Russian incarcerated male juvenile delinquents. In addition,
      alcohol use, personality, and parenting factors were assessed by self-reports.
      RESULTS: Alcohol-abusing delinquents (n=138) scored significantly higher on
      novelty seeking and maternal emotional warmth and reported higher levels of
      psychopathology, as compared to nonalcohol-abusing delinquents (n=91). Logistic
      regression analysis demonstrated that personality and parenting factors were
      significantly related to alcohol abuse, even after controlling for comorbid
      psychopathology. CONCLUSION: Alcohol-abusing delinquents are at risk for a wide
      spectrum of psychiatric disorders. Alcohol abuse is associated with personality
      and parenting factors independently of comorbid psychopathology. Early
      interventions with high-risk youths may help to reduce their psychiatric problems
      and alcohol abuse.

PMID- 15981138
TI  - Group crisis intervention for children during ongoing war conflict.
AB  - The aim of this study was to evaluate the short-term impact of a group crisis
      intervention for children aged 9-15 years from five refugee camps in the Gaza
      Strip during ongoing war conflict. Children were selected if they reported
      moderate to severe posttraumatic stress reactions, and were allocated to group
      intervention (N=47) encouraging expression of experiences and emotions through
      storytelling, drawing, free play and role-play; education about symptoms (N=22);
      or no intervention (N=42). Children completed the CPTSD-RI and the CDI pre- and
      post-intervention. No significant impact of the group intervention was
      established on children's posttraumatic or depressive symptoms. Possible
      explanations of the findings are discussed, including the continuing exposure to
      trauma and the non-active nature of the intervention.

PMID- 15981139
TI  - Cognitive impulsivity in specific learning disabilities.
AB  - Many studies on cognitive impulsivity in learning disabled children have been
      criticized for their methodological limitations, and they have not dealt with the
      different types of learning disability. The aim of this study was to overcome
      these limitations and to assess if there was a significant cognitive impulsivity
      in reading disorder and/or spelling disorder by using the 20-item Matching
      Familiar Figures Test (MFF20). A total of 110 children (second through eighth
      grades) were recruited from a cohort of children assessed for the first time in a
      National Health clinic specialized in the study of specific learning
      disabilities. In all, 30 dyslexic children and 25 children with spelling disorder
      (all children without an ADHD comorbidity) were compared with 55 children of a
      control group on the MMF20 (accuracy and time latency). Results showed that the
      children with reading disorder were less accurate than the children with spelling
      disability (p<0.05). Both these groups performed less accurately than the control
      group. Subjects with dyslexia were faster than both the other groups in response
      time (p<0.05), clearly showing a significantly higher cognitive impulsivity than
      the other groups. Hence, data seem to confirm the idea that, similar to ADHD
      children, dyslexic children have impaired frontal/prefrontal functions. Clinical
      and treatment implications are discussed.

PMID- 15981140
TI  - Psychopathological distress predicts suicidal ideation and self-harm in
      adolescent eating disorder outpatients.
AB  - OBJECTIVE: This study evaluated the differences in suicidal behaviour between
      adolescent anorexia nervosa (AN) and bulimia nervosa (BN), and the association of
      age, menarche timing, duration of eating disorder (ED), depression and general
      psychopathological symptoms (GSI) with suicidal behaviour in adolescent ED.
      METHODS: The study group comprised 57 adolescent outpatients (girls) attending
      for assessment because of eating disorders. Suicidal ideation, deliberate self
      harm and suicidal attempts were assessed in self-report questionnaires. RESULTS:
      In both ED groups, one adolescent had attempted suicide before assessment.
      Suicidal ideation and/or deliberate self-harm were reported in over half of the
      cases. Bulimics had significantly more suicidal ideation and deliberate self-harm
      than anorectics. In multivariate analysis, BN and depression predicted suicidal
      ideation, but only GSI persisted as predicting deliberate self-harm. CONCLUSIONS:
      Suicidal behaviour is common in adolescent ED. Type of ED (BN), depression and
      higher GSI are strongly associated with suicidal ideation and deliberate self
      harm. Our results point to the need to evaluate psychopathological symptoms in
      adolescent ED, especially in BN, in the initial assessment to prevent severe
      suicidal behaviour.

PMID- 15981141
TI  - Differential contextual factors of comorbid conduct and depressive disorders in
      Spanish children.
AB  - OBJECTIVE: The aim of this study was to clarify the validity of the mixed
      conduct/depressive disorder in young people to justify its place in ICD-10 by
      examining a wide range of risk factors, school performance and other contextual
      variables. METHOD: Data on risk factors and other school and family variables
      were compared between 66 referred children with depressive disorders without
      conduct disorder, 135 with conduct or oppositional defiant disorder without
      depressive disorders, and 90 with both. Data were obtained through structured
      diagnostic interviews with parents and children and questionnaires. RESULTS:
      Marked differences emerged between depressive and comorbid groups in rearing
      style, school and friends. Comorbid conduct-depression and pure conduct disorders
      share similar contextual factors; the differences are larger in school, where the
      pure conduct group has more difficulties. CONCLUSIONS: Based on contextual
      factors, pure depression is different from conduct-depressive disorder, but pure
      conduct disorder is similar to the comorbid condition. The results have
      implications for nosology and treatment of these disorders.

PMID- 15981142
TI  - Comorbidity of Asperger syndrome and gender identity disorder.
AB  - The case of a 35-year-old biological woman with Asperger syndrome (AS) and gender
      identity disorder (GID) fulfilling DSM-IV criteria is reported. Against the
      background of recently emerging theories of cognitive male pattern underlying
      autism we present additional psychological assessments in order to discuss any
      possible interaction or discrimination between AS and GID. Whilst we explain GID
      as a secondary feature of AS, we examine the assumption of the necessity of
      treating GID in AS as a primary GID in accordance with international standards.
      We consider the treatment of GID as compelling, particularly because curative
      therapy for AS is lacking and with GID treatment in this vein, the patient gains
      psychosocial improvement.

PMID- 15981144
TI  - [Is there any alteration in bone mineral density in patients with depression?].
AB  - OBJECTIVE: Depression is associated with some alterations in behavior and
      hypothalamic-pituitary-adrenal axis function that may be risk factors for
      decreased bone mineral density (BMD). There is considerable inconsistency as to
      whether depressed patients really have decreased BMD or not. Decreased BMD has
      been reported in patients suffering from major depression in some studies, but
      not in some others. Moreover, few studies have investigated BMD in male depressed
      patients. The aim of this study was to investigate BMD in patients with major
      depression, including male ones. METHOD: BMD was investigated in forty-two
      inpatients that fully met the DSM-IV criteria for major depressive disorder (21
      women, 21 men; mean age+/-SD: 37.57+/-8.70) and compared with that in twenty
      three healthy controls (12 women, 11 men; mean age+/-SD: 33.73+/-7.16). The
      severity of clinical symptomatology was assessed by the Montgomery-Asberg
      Depression Rating Scale (MADRS). BMDs of lumbar vertebrae (L1-L4) and femur neck
      were measured using dual energy X-ray absorptiometry. RESULTS: We found no
      difference in the values of BMDs of lumbar vertebra (L1-L4) and femur neck
      between depressive patients and controls among women or men. However, BMDs of the
      males in the control group were higher than those of the healthy females for both
      regions investigated; this gender difference was not observed in the depressive
      patients. CONCLUSION: Major depression is not associated with any alteration in
      BMD either in women or in men.

PMID- 15981145
TI  - [Teaching empathy in medical education].
AB  - OBJECTIVES: To determine whether there is any difference in empathic tendencies
      and attitudes towards communication in medical practice among the first-year
      students of Adnan Menderes University Medical School, and to determine the effect
      of education and the relation between these two features. METHOD: The Empathic
      Tendency Scale and Attitudes Towards Communication in Medical Practice
      Questionnaire were used to collect data from 36 (55.3 % of the total) students
      (65.7 % female; mean age: 18.3). RESULTS: Students are clustered into two groups
      for both scales using K-means analysis, which was used to see whether the
      students were homogeneous regarding empathy and communication attitudes at the
      beginning of the teaching period. According to the Empathic Tendency Scale
      results 25% of students have a high empathic tendency (HET) and 75% have a low
      empathic tendency (LET) and the results of the Attitudes Towards Communication in
      Medical Practice Questionnaire indicated that 56% have positive and 44% have
      negative attitudes towards communication. However, the difference between the pre
      and post-teaching results of either group seems to show a tendency towards change
      (p< 0.10). The change has a negative and a positive tendency in the HET and LET
      groups, respectively. CONCLUSION: Our results seem to verify the predicted
      differences among the students in their empathic tendencies and attitudes towards
      communication in medical practice. It seems that empathic tendency is more likely
      to be changed by an appropriate teaching technique when change within the groups
      is concerned.

PMID- 15981146
TI  - [Somatic symptoms of depression].
AB  - OBJECTIVE: The somatic component of depression is an important clinical
      phenomenon. The role of somatic amplification, alexithymia, anger and symptom
      attribution has been investigated in the genesis of the somatic symptoms of
      depression. METHOD: The study was carried out with 32 patients attending the
      outpatient psychiatry clinics of Karadeniz Technical University Medical School,
      meeting the diagnosis of depression according to DSM-IV, and 34 healthy subjects.
      The subjects were assessed with the Beck Depression Scale, the Beck Anxiety
      Scale, the Hamilton Depression Scale, the Hamilton Anxiety Scale, the
      Somatosensory Amplification Scale, the 20-item Toronto Alexithymia Scale the
      Spielberger State-Trait Anger Expression Inventory, the Symptom Interpretation
      Questionnaire and a data form for recording sociodemographic characteristics.
      RESULTS: The sociodemographic characteristics of the sample were similar. The
      anxiety, alexithymia, and anger-in scores were significantly higher, while anger
      control scores were significantly lower in the depressive subjects.
      Psychologizing attributes were positively correlated with depression and anxiety.
      Normalizing was negatively correlated with anxiety. Somatizating was correlated
      with the difficulty in identifying feelings subscale of alexithymia. DISCUSSION:
      These findings show that depressive patients are more alexithymic, have more
      difficulty in controlling their anger and introject their anger more compared to
      the healthy controls. Depressed and anxious subjects psychologize, and subjects
      with difficulty in identifying emotions somatize their symptoms.

PMID- 15981147
TI  - [The multidimensional relationship questionnaire: a study of reliability and
      validity].
AB  - PURPOSE: The Multidimensional Relationship Questionnaire (MRQ) was developed to
      measure psychological tendencies associated with intimate relationships by Snell
      Schicke and Arbeiter (2002). The purpose of the present study was to investigate
      the reliability and validity of the Turkish version of the Multidimensional
      Relationship Questionnaire. METHOD: 480 university students from various
      faculties, with a history of involvement in an intimate relationship at present
      or in past (308 female, 172 male) participated in the study. The Relationship
      Assessment Scale (RAS) was used for the criterion validity. RESULTS: In order to
      determine the construct validity of MRQ, factor analysis was conducted using
      principal components analysis with varimax rotation. The factor analysis resulted
      in eight factors;focus on relationship extremely, relational satisfaction, fear
      of relationship/relational anxiety, relational monitoring, relational esteem,
      external relational control, relational assertiveness, and internal relational
      control. The correlation coefficients of the MRQ with RAS were between -.41 and
      .69. The Cronbach's alpha for the MRQ was .81. The computed test-retest
      reliability coefficient was .80. MRQ subscales were found to show significant
      difference, with respect to sex of the participant, only in the subscale of
      "external relational control". CONCLUSION: Analysis demonstrated that MRQ had a
      satisfactory level of reliability and validity in Turkish university students.

PMID- 15981148
TI  - [The effect of day and night shift working on the attention and anxiety levels of
      anesthesia residents].
AB  - OBJECTIVE: To evaluate the attention, learning and memory related cognitive
      functions after 12-hour day versus night shift-work in anaesthesia residents.
      METHOD: Fifteen residents working on the day shift and 18 working on the night
      shift volunteered. All were interviewed with the Rey Auditory Verbal Learning
      Test (AVLT), Visual Aural Digit Span Test (VADST), and State Trait Anxiety
      Inventory (STAI) before and after the shifts. Residents' self-evaluations of
      their fatigue, stress, sleep quality and duration of sleep were sought. RESULTS:
      The two groups were similar regarding age, gender, attention, fatigue, stress,
      affection, sleep quality and duration of sleep. The number of words learned in
      the first trial of the Rey AVLT decreased after the shifts in both groups. Before
      the night shift the word list could be learned more effectively and with fewer
      trials compared to the pre-day shift. The learning deteriorated, and repetitions
      and forgotten words increased after the night shift. The aural oral, aural
      written and visual written subtest scores deteriorated after the night shift.
      State anxiety levels did not differ between the night and day shift groups or
      before and after the shifts. CONCLUSION: The cognitive functions of residents may
      be impaired after the night shift. We think that close supervision of residents
      and provision of more rest for them during night shifts would be beneficial in
      decreasing their errors, which may affect patients.

PMID- 15981149
TI  - [The elderly, nursing homes and life voyages: a psychodrama group study].
AB  - OBJECTIVE: To investigate the applicability of psychodrama orientated group work
      among the elderly living in nursing homes, and effect of this group work on
      coping with psychological and behavioral problems. METHOD: Eleven male volunteers
      were chosen for the group. None of them had any negative features on
      communicating with others or had somatic or serious psychological problems.
      Eighteen psychodrama orientated group work sessions were held. Each was 2.5 to 3
      hours long and took place only once a week. The staff of the nursing home became
      involved in the process after the twelfth session. Therapists registered their
      observations at every meeting. To evaluate the anxiety-depression levels the
      Geriatric Depression Scale and Hamilton Anxiety Rating Scale were used. RESULTS:
      Due to a late warm up among the members in this group, dramatization took place
      in later sessions. During the study, an increase in the members' spontaneity,
      creativity and empathy and consequently an improvement in communicating with and
      helping others, and coping with problems were observed. Articulation of emotions
      and thoughts improved gradually during the study. Somatic and total anxiety
      scores decreased significantly. CONCLUSION: This study shows that psychodrama
      group work can be used with the elderly and it may be helpful for improving
      psychological and behavioral areas, and for discovering the meaning of life.

PMID- 15981150
TI  - [Neuropsychology of attention deficit hyperactivity disorder: relevant theories
      and empirical studies].
AB  - There is a rapidly accumulating body of knowledge related to the neurobiology of
      Attention Deficit Hyperactivity Disorder (ADHD) stemming from multidisciplinary
      neuropsychological and neuroimaging studies. This paper is a review of recent
      knowledge in the context of neuropsychological theory and research in this area.
      The final section of the article introduces animal models on the subject. It has
      been emphasized that the controversy regarding the results of neuropsychological
      studies is semantic rather than substantive. The semantic issue here is believed
      to be that the term "attention" has to be related to more than one anatomical
      network among several brain regions. ADHD, which has many cognitive and
      behavioral dimensions like attention deficit, hyperactivity and impulsivity, has
      a heterogeneous nature reflecting the neurobiological basis related to parallel
      information processing models. Based on clinical and neuropsychological data it
      has been stated that both the orbitofrontal cortex and dorsolateral prefrontal
      cortex are functionally disturbed in ADHD. However, whether these functional
      disturbances are related to the prefrontal cortex or other brain regions
      associated however primarily with this cortex is yet unclear. Dopamine and
      epinephrine as neurochemical factors and the frontal lobe and basal ganglia as
      anatomical factors have been found to be especially responsible. Valid
      endophenotypic features should be determined in order to specify genetic subtypes
      of neuropsychiatric syndromes. A review of the literature leads us to the
      conclusion that tests used to assess attentional components like the executive
      control network and behavioral inhibition could determine valid endophenotypes.

PMID- 15981151
TI  - [A case of diaper fetishism].
AB  - Some people cannot obtain satisfaction from ordinary sexual relationships;
      instead they prefer alternative methods. They are referred to in psychiatric
      terminology as paraphiliacs. Fetishism is a type of paraphilia in which a person
      is sexually attracted to objects and some body parts. Most fetishists do not
      intend to cause harm to other people, but may have problems when others become
      involved in the problem. Underlying personality disorders extending through
      childhood are thought to be the source of the etiology. Perverted people do not
      wish to change their behavior pattern. They never seek treatment from a
      therapist. Psychological issues obviously play a crucial role in determining the
      choice of paraphilia and the underlying meaning of the sexual acts. Psychodynamic
      models (object relations theory, self psychology, drive theory) can shed light on
      the meaning of a perversion. In this case report, a 22- year-old man with diaper
      fetishism is presented. When family dynamics are considered, the mother has been
      described as psychologically distant from her son. The fetish object was
      recognized during childhood at around the age of four. During puberty, the fetish
      object became sexually attractive. Our patient exhibited his first perverted
      behavior when he was six years old. Later, he could control this behavior. At the
      age of twelve, the perverted behavior became sexually arousing. This paper
      emphasizes the diaper fetishism case through the patient's past psychiatric and
      medical history. Diaper fetishism is discussed in the light of forensic,
      cognitive and psychodynamic theories.

PMID- 15981153
TI  - [Influence of nocturnal hypoxemia on the function of the visual tract in the
      course of the obstructive sleep apnea syndrome].
AB  - BACKGROUND AND PURPOSE: In patients with obstructive sleep apnea (OSA) syndrome
      the episodes of upper airway obstruction lead to hypoxemia during sleep. The aim
      of the study was to establish the influence of sleep hypoxemia on the function of
      the visual tract in OSA patients. MATERIAL AND METHODS: The latency and amplitude
      of wave P100 of visual evoked potentials have been studied in 35 patients with
      OSA syndrome (mean apnea index 48+/-19). The diagnosis of OSA was established on
      the basis of continuous recordings of the respiratory function during sleep with
      additional full polysomnography in 17 patients. RESULTS: Mean absolute latency of
      P100 was longer in OSA patients than in healthy controls (117.0+/-8.8 ms vs.
      104.3+/-4.6 ms, p<0.001). The differences in the amplitude of P100 were not
      significant (5.9+/-2.6 mV in OSA patients and 7.62+/-3.04 mV in healthy persons).
      In 60% of patients the latency of P100 exceeded 118 ms; in this group of patients
      the mean SaO2 during sleep apneas was lower than in patients with normal P100
      latency (46+/-15% vs. 69+/-10%, p<0.05). Full polysomnographic studies revealed
      that in patients with prolonged latencies as compared with patients with normal
      P100 latencies there were lower: minimal SaO2 during NREM sleep (63+/-12% vs.
      78+/-8%, p<0.05), as well as mean and minimal SaO2 during REM sleep (53+/-15% vs.
      80+/-5% and 46+/-15% vs. 69+/-10%, p<0.05), without differences in apnea index or
      apnea duration. CONCLUSIONS: In patients with OSA syndrome the
      electrophysiological abnormalities suggesting damage of the optical tract may
      develop probably as a consequence of profound sleep hypoxemia.

PMID- 15981152
TI  - [Influence of estrogens on the impedance of cerebral blood vessels].
AB  - BACKGROUND AND PURPOSE: Recent experimental research has demonstrated the
      neuroprotective effect of estrogen on the ischemic brain. There is, however,
      little data available concerning the effects of estrogen on cerebral circulation
      in humans. In this contribution we studied the influence of endogenous estrogen
      on the flow in the carotid arteries and on the cerebrovascular impedance.
      MATERIALS AND METHODS: The plasma concentration of 17-beta-estradiol was measured
      in 19 healthy, young women over 10 days of the menstrual cycle (days 3, 6, 10, 13
      17, 20 and 24). Ultrasound examination of the carotid arteries was performed on
      the same days using a Toshiba Aplio ultrasound system endowed with a 7.5 MHz
      linear transducer. Impedance indices based on the recorded systolic, mean and end
      diastolic blood flow velocities were calculated for the internal, common and
      external carotid arteries. RESULTS: During the follicular phase of the menstrual
      cycle, blood flow in the internal carotid artery increased considerably in all
      subjects along with increasing plasma concentrations of estrogen. The end
      diastolic blood flow velocity increased most significantly, on average by 16% and
      by up to 24% in individual cases. At the same time, the impedance indices
      (resistance index--RI and pulsatility index--PI) decreased significantly from
      their base values. Blood flow velocity in the common carotid artery, the caliber
      of this vessel, pulse rate and blood pressure remained stable during the entire
      follicular phase of the cycle. Nevertheless, the flow velocity in the external
      carotid artery decreased. This suggests that an increase in the cerebral blood
      flow, promoted by decreasing cerebro-vascular impedance in the follicular phase
      of the cycle, occurs at the expense of blood "stolen" from the external carotid
      artery. CONCLUSION: Estrogen increases blood flow in the internal carotid artery
      by decreasing the impedance of cerebral microcirculation.

PMID- 15981154
TI  - [Occipitocervical fixation in the surgical treatment of pathologies of the
      craniovertebral junction].
AB  - BACKGROUND AND PURPOSE: New surgical approaches to the tumors of the skull base
      necessitate removal of certain bone structures of the base. In the case of the
      transcondylar far-lateral approach, the whole occipital condyle and lateral mass
      of C1 are removed resulting in iatrogenic instability. Consequently, an
      occipitocervical fixation is needed. The aim of the study was to assess the
      usefulness of the CCD cervical system for the occipitocervical fixation in the
      surgery of the tumors of the craniovertebral junction. MATERIAL AND METHODS: The
      authors present the application of the CCD cervical system produced by Medtronic
      Sofamor-Danek in three patients who underwent surgery of tumors of the foramen
      magnum, clivus or craniovertebral junction. The system consists of two titanium
      rods, which adjusted to the curvature of the spine and the occiput, are fixed by
      laminar cervical and occipital hooks, fixed to the trepanation hole edge or the
      edge of the foramen magnum. It is also possible to use screws driven to the
      occipital bone if it is more than 7 mm thick. RESULTS: The system fixation is
      simple and relatively short. Good stabilization was achieved in all patients. No
      complications caused by the implants have been observed. CONCLUSIONS: The CCD
      cervical system can be successfully used for the occipitocervical fixation in a
      lateral transcondylar approach and in the cases of other non-traumatic
      craniocervical instability. It is especially recommended in cases of unusual
      thinning of the occipital bone or in osteoporotic states.

PMID- 15981156
TI  - [Intraoperative assessment of cognitive and executive functions in patients with
      brain tumors].
AB  - BACKGROUND AND PURPOSE: The aim of this paper was to evaluate the usefulness of
      selected methods of intraoperative neuropsychological assessment. In order to
      investigate the influence of the direct cortical stimulation and tumor resection
      on the patients' intraoperative performance, we examined selected areas of
      cerebral cortex involved in cognitive activity in patients undergoing awake
      craniotomy for brain tumors. MATERIAL AND METHODS: The analyzed group consisted
      of 21 patients (11 men, 10 women) with tumors located in eloquent areas of the
      left hemisphere. All patients had intact understanding of speech and relatively
      minor neurological deficits. We applied both experimental methods as well as
      certain standardized tests (WAIS-R, AVLT) for the investigation of verbal and
      nonverbal functions. The tests were performed during direct cortical stimulation
      and tumor resection, and also before and one week after the operation. RESULTS:
      Verbal areas were identified in 10 patients, sensorimotor strip in 3, whereas
      both of them in 3. Even though in 5 out of 21 subjects we were unable to identify
      the eloquent cortex, there was no difference between pre- and postoperative
      assessment in these patients. Similarly, there was no statistically significant
      difference in pre- and postoperative tests among patients with successful
      cortical mapping. CONCLUSIONS: We showed that the presented methods of
      intraoperative assessment of cognitive activity were useful and appropriate for
      the identification of the eloquent areas of the brain.

PMID- 15981157
TI  - [Cognitive and affective disturbances in children after surgical treatment of
      cerebellar tumors].
AB  - BACKGROUND AND PURPOSE: The cerebellum has been associated with motor control,
      but more recent studies have extended its contribution to other functions, such
      as modulation of emotions, behavioral organization or language. The cerebellar
      cognitive affective syndrome was described primarily in adults. In children,
      cerebellar lesions are relatively frequent and some are due to neoplasm. MATERIAL
      AND METHODS: Cognitive and emotional functions were studied in 66 children who
      underwent surgery for cerebellar pilocytic astrocytoma at the Department of
      Neurosurgery of the Children Memorial Health Institute. 36 children were
      psychologically examined and parents of 66 children filled in a questionnaire,
      answering questions about children's linguistic functioning, emotion regulation
      and ability to initiate, organize and efficiently realize various activities.
      RESULTS: The disturbances in the initiation and realization of activities were
      reported most often (77%). Problems in emotional regulation were noticed in 65%
      of children and were characterized by disinhibition, impulsivity and
      irritability. Language difficulties were observed in 42%. No significant
      differences between groups of children with different localization of tumor
      (vermis or cerebellar hemisphere) were observed. CONCLUSIONS: The present study
      confirms the psychological deficits following cerebellar lesion in children,
      similar to the cerebellar cognitive affective syndrome reported in adult
      patients.

PMID- 15981158
TI  - [Change of interleukin-4 and interleukin-12 levels after therapy of multiple
      sclerosis relapse with methylprednisolone].
AB  - BACKGROUND AND PURPOSE: In the pathomechanism of multiple sclerosis (MS), a vital
      role is attributed to autoimmune responses. Higher activity of the disease is
      connected with an increased activity of proinflammatory cytokines while in
      remissions anti-inflammatory cytokines dominate. The aim of the study was to
      evaluate the effects of methylprednisolone treatment on the level of IL-4 and IL
      12 and to determine whether their levels are related to the degree of disability
      and may be prognostic factors in the assessment of relapse sequelae. MATERIAL AND
      METHODS: The study included 32 patients with MS (according to McDonald's
      criteria) with relapses and remissions (17 patients with relapse who received
      methylprednisolone in the dose of 1.0 g i. v. on 5 consecutive days and 15
      patients in remission). The control group consisted of 15 patients with non
      inflammatory diseases of the nervous system. The levels of cytokines were
      determined by ELISA method using the Pharmingen kits. The examinations of
      patients in relapse were conducted before and after steroid therapy; the
      remaining patients were examined only once. RESULTS: In the relapse a visible
      increase in serum IL-12 level (p<0.05) was observed; its level after
      methylprednisolone treatment was found to be significantly decreased (p<0.001).
      The level of IL-4 was not significantly affected by steroid therapy. There was no
      relation between the severity of disability and cytokine levels. CONCLUSIONS: The
      level of IL-12 increases in MS relapses and decreases after methylprednisolone
      therapy. The changes in IL-4 and IL-12 levels are the manifestations of
      inflammatory reactions connected with the relapse; however, they do not directly
      indicate the extent of damage to CNS. They cannot be treated as a prognostic
      factor allowing to anticipate the consequences of the relapse.

PMID- 15981159
TI  - [Prognostic value of computerized rheoencephalography in chronic posttraumatic
      subdural hematoma: a preliminary report].
AB  - BACKGROUND AND PURPOSE: The results of treatment of chronic subdural hematoma
      (CSDH) are still regarded as unsatisfactory. Measurements of cerebral
      hemodynamics are increasingly used to elucidate the pathophysiology of mental
      disturbances and hemiparesis in CSDH. On the other hand the clinical studies of
      cerebrovascular autoregulation in this condition are almost nonexistent. This
      study was therefore conducted to assess the cerebral artery compliance and the
      status of the autoregulatory reserve in CSDH as well as their effect on the
      neurological outcome. MATERIAL AND METHODS: Ten patients with posttraumatic CSDH
      were studied. The status of cerebrovascular autoregulation and compliance of
      arteries were investigated using computerized rheoencephalography (REG). A
      classification of the pulse waveform (REGpw) has been devised according to the
      number of inflection points in the ascending branch. The normal cases have
      corresponded with only one inflection point (category I). The presence of three
      or more inflection points was thought as characteristic for regressive changes of
      the arterial wall (category II). The capacity of autoregulatory reserve was
      estimated by studying the changes in amplitude of REGpw as a response to upper
      body-down tilting. RESULTS: In all patients the REG examination revealed a
      reduction in autoregulatory reserve. In 3 patients with the worst clinical result
      of treatment bilateral impairment of cerebrovascular autoregulation was found.
      The reduction in compliance of arteries was revealed in 6 patients. CONCLUSIONS:
      Our preliminary results indicate that bilateral impairment of the cerebral blood
      flow and the decrease in arterial compliance are of prognostic significance in
      patients with CSDH.

PMID- 15981160
TI  - [Supplementation of cranial defects by an autologous bone flap stored in the
      abdominal wall].
AB  - BACKGROUND AND PURPOSE: The aim of this paper is to present an alternative method
      of cranioplasty with the use of an autologous cranial bone flap stored between
      primary and restorative surgery in the subcutaneous pocket in the lateral
      hypogastric region. MATERIAL AND METHODS: Between January 1999 and April 2002, in
      the Department of Neurosurgery of Medical University of Lodz we performed 36
      procedures of the bone flap implantation into the abdominal subcutaneous fat
      tissue. These procedures followed craniectomy, mainly in cases of acute subdural
      hematomas and ruptured intracranial aneurysms. RESULTS: After storage, the bone
      flap was reimplanted in 28 patients. The mean time between operations was 14 days
      (range 8-53 days). In the cranioplasty group we had only one infection of the
      bone flap. Among patients excluded from the bone flap restoration we observed one
      inflammatory complication in the abdominal wall and one subcutaneous hematoma
      requiring evacuation. CONCLUSIONS: In our opinion, the presented method of the
      cranial defect's supplementation may be competitive to procedures utilizing
      synthetic prostheses in the population of patients for whom reimplantation of the
      bone flap will be expected in 2-3 months after the primary operation. Advantages
      of the procedure are: the autologous bone graft, the excellent cosmetic effect,
      low costs of the procedure and low rate of inflammatory complications.

PMID- 15981162
TI  - [Fragile X-associated tremor/ataxia syndrome].
AB  - Carriers of premutation within the FMR1 gene are typically normal intellectually,
      although a limited number of them have been reported to have either learning
      disabilities or mild dysmorphic features. A neurological condition involving
      intention tremor, ataxia and cognitive decline has recently been identified among
      older males carrying premutation alleles of the FMR1 gene, including grandfathers
      of children affected with fragile X syndrome. Characteristic findings from
      magnetic resonance imaging include cerebral and cerebellar volume loss and
      altered signal intensities of the middle cerebellar peduncles. This syndrome may
      represent one of the more common causes of tremor, ataxia and dementia among
      older males. The diagnosis of FXTAS is straightforward if a family at high
      genetic risk could be identified. Thus genetic counseling should be offered to
      such family.

PMID- 15981163
TI  - [Guillain-Barre Syndrome and its association with infectious factors].
AB  - Guillain-Barre Syndrome (GBS) is an acute polyneuropathy often triggered by
      inflammatory and probably autoimmune mechanisms. Development of GBS is in 2/3 of
      cases preceded by acute infection, typically with gastrointestinal or respiratory
      symptoms. Infectious agents related to GBS include cytomegalovirus, Epstein-Barr
      virus, Campylobacter jejuni, Mycoplasma pneumoniae and Haemophilus influenzae.
      Molecular mimicry seems to be responsible for GBS development after infection,
      through the synthesis of autoantibodies against myelin gangliosides. Autoimmune
      reactions develop only in a small fraction of all exposed individuals, depending
      on still unresolved factors. Different infections lead to forms of GBS differing
      in spectrum of autoantibodies and in frequency with which different clinical
      symptoms appear. This may be of some significance for early prognosis and in
      future possibly for choosing therapeutic options. An increased risk of GBS may be
      also related to vaccination, but with presently used vaccines this increase
      remains below one case of GBS per one million doses.

PMID- 15981164
TI  - [Motor cortex stimulation in the central pain syndrome].
AB  - We present a case of a 45-year-old male, treated with motor cortex stimulation
      (MCS). The procedure was performed in order to decrease symptoms of the central
      pain syndrome (CPS), which developed seven years earlier, after a left-side,
      cerebellum and brainstem ischemic stroke. The syndrome is defined as pain due to
      primary damage or dysfunction of the central nervous system. The pain was not
      sensitive to pharmacological and previous surgical interventions. During four
      months of follow-up after surgery with the use of MCS, 20% reduction of pain
      (Visual Analog Scale), withdrawal of narcotic and decrease of non-narcotic
      medications, ability to introduce rehabilitation and improvement of sleep were
      observed. No side effects were noticed. The procedure of electrode implantation
      to motor cortex is a relatively new treatment option in refractory central and
      neuropathic pain syndromes. The number of described procedures does not exceed
      500 worldwide. The presented case is to our knowledge the first procedure of its
      type in Poland, giving hope to CPS patients, whose symptoms are otherwise
      difficult to treat.

PMID- 15981166
TI  - [Moyamoya disease associated with stenosis of extracranial arteries: a case
      report and review of the literature].
AB  - We report on a 6-year-old boy with a 2.5-year history of recurrent cerebral
      ischemic strokes and moderate systemic hypertension. Brain angio-MR examination
      revealed stenosis of cerebral arteries with a network of collateral vessels that
      are characteristic features for moyamoya disease. However, further examination,
      including angio-CT of abdominal vessels, revealed a significant stenosis of the
      aorta, celiac trunk and bilateral renal arteries. As the literature shows worse
      prognosis for moyamoya hypertensive patients having their blood pressure reduced,
      our patient, though hypertensive, remains disqualified for blood pressure
      reduction.

PMID- 15981167
TI  - [Diagnostic difficulties due to atypical symptoms in normal pressure
      hydrocephalus. A case report].
AB  - This paper presents a case of a female patient with unusual symptoms of diagnosed
      hydrocephalus. Symptoms demonstrated by the patient were initially diagnosed as
      immature personality, after that she was diagnosed with reactive depressive
      disorders. For those reasons she was treated for over 20 years in different
      psychiatric outpatient clinics and psychiatric hospitals. She was treated
      pharmacologically with different medications: antidepressants, neuroleptics etc.
      She also participated periodically in individual and group psychotherapy.
      Computed tomography performed after the loss of consciousness with significant
      motor deficits revealed relevant dilation of the cerebral ventricular system. The
      neuropsychological examination revealed disturbances in emotional-motivation area
      and cognitive deficits. Those disorders caused significant problems in social and
      professional activities. After completing the diagnosing process the patient was
      diagnosed with arrested hydrocephalus. Results of clinical examinations suggested
      that at this stage of the disease there are no indications for shunt
      implantation. Probably earlier diagnosis could bring a chance of successful
      neurosurgical intervention and definitely more efficient therapy.

PMID- 15981168
TI  - [Diagnostic problems in a case of multiple sclerosis with predominance of
      psychiatric symptoms].

PMID- 15981169
TI  - [Regarding the article by W. Berny i wsp. entitled "Expression of PCNA, Ki-67,
      AgNOR and p53 protein in brain glial tumors", published in the Polish Journal of
      Neurology and Neurosurgery no. 6/2004].

PMID- 15981170
TI  - T-cell and chemokine receptor variation in south Amerindian populations.
AB  - The immune response of relatively small, endogamous populations is of special
      interest, because they may differ from those of large, ethnically diverse, urban
      groups. As a contribution to this area of investigation, we tested 99 individuals
      from two Brazilian native populations for two T-cell receptor gene segments
      (TCRBV3S1 and TCRBV18) and 241 subjects from eight tribes of this ethnic group in
      relation to the chemokine receptor CCR5delta32 allele. Differences in TCRBV3S1
      and TCRBV18 prevalences of the Amerindians in relation to European- and African
      derived individuals were not marked. We confirmed the absence of the CCR5delta32
      allele in most groups, its presence in the Mura and Kaingang, probably because of
      European gene introgression.

PMID- 15981171
TI  - Antimicrobial activity and tightness of a DCPD-CaO-based hydraulic calcium
      phosphate cement for root canal filling.
AB  - Calcium hydroxide is currently used in dentistry for endodontic treatments where
      its main advantage is its antibacterial and anti-inflammatory activity. However,
      it also has some drawbacks such as pulp necrosis, slight solubility, slow and
      insufficient hardening, and retraction on drying. In consequence, it is used only
      as temporary material for root canal disinfection. By mixing calcium hydrogen
      phosphate dihydrate (CaHPO4 . 2H2O, also called dicalcium phosphate dihydrate,
      DCPD) and calcium oxide with a sodium phosphate buffer as liquid phase, we
      obtained a CPC with better mechanical properties than calcium hydroxide pastes.
      The setting reaction produced either hydroxyapatite (HA) or a mixture of HA and
      calcium hydroxide depending on the relative masses of DCPD and CaO in the cement
      powder. The presence of calcium hydroxide a priori confers antimicrobial
      properties to this cement which were investigated in agar plates (diffusion
      method) against Streptococcus mutans, Lactobacillus acidophilus, Candida
      albicans, Enterococcus faecalis, Staphylococcus hominis (clinical isolates), and
      a preparation of polymicrobial flora isolated from dental plaque. The cement
      samples tested were prepared at molar calcium-to-phosphate ratios (Ca/P) of 1.67
      to 2.75. A pure calcium hydroxide paste was used as reference material. Clear and
      reproducible bacterial growth inhibition was observed for cement samples with
      Ca/P > or = 2 against all the microorganisms tested. With Ca/P = 2.5, this cement
      alkalinizes dentinal tubules and provides a fluid-tight sealing that well
      compares with sealing obtained using a zinc oxide-eugenol cement without gutta
      percha point. DCPD-CaO-based cement is therefore a potential root canal filler.

PMID- 15981172
TI  - The contradictory effects of pores on fatigue cracking of bone cement.
AB  - The beneficial effect of porosity reduction on the fatigue life of bone cement
      has been demonstrated in numerous experimental studies. Clinically, however, it
      seems that the beneficial effect of porosity reduction of cement around total hip
      replacement components can only be found in large follow-up studies. Little is
      known about the actual mechanical effect of a pore on fatigue crack formation in
      cement mantles. We studied the effect of pores on the crack formation process in
      a finite element model of a transverse slice of a total hip reconstruction. We
      created models with a single large pore and models with multiple pores at levels
      of 2, 4, and 9%. The models were cyclically torque-loaded, causing macrocracks to
      appear in the cement mantle. In all models, we found that pores acted as
      microcrack initiators. However, pores could have both a detrimental and a
      beneficial effect on the macrocrack propagation in the cement mantle. Both
      effects were seen in the models with a single large pore and in the models with
      multiple pores. Pores would either accelerate, deviate, or decelerate the
      macrocrack propagation in the cement mantle. The effect of the pores depended on
      the location of the pores with respect to the stress intensities in the model,
      but was independent of the pore size or the level of porosity. The results may
      explain why the beneficial effect of vacuum mixing is difficult to demonstrate
      clinically. Stress intensities that are present in a cement mantle in an in vivo
      situation may overshadow the detrimental effect of a pore, while the beneficial
      effect may become more pronounced.

PMID- 15981173
TI  - Three-dimensional printing of porous ceramic scaffolds for bone tissue
      engineering.
AB  - This article reports a new process chain for custom-made three-dimensional (3D)
      porous ceramic scaffolds for bone replacement with fully interconnected channel
      network for the repair of osseous defects from trauma or disease. Rapid
      prototyping and especially 3D printing is well suited to generate complex-shaped
      porous ceramic matrices directly from powder materials. Anatomical information
      obtained from a patient can be used to design the implant for a target defect. In
      the 3D printing technique, a box filled with ceramic powder is printed with a
      polymer-based binder solution layer by layer. Powder is bonded in wetted regions.
      Unglued powder can be removed and a ceramic green body remains. We use a modified
      hydroxyapatite (HA) powder for the fabrication of 3D printed scaffolds due to the
      safety of HA as biocompatible implantable material and efficacy for bone
      regeneration. The printed ceramic green bodies are consolidated at a temperature
      of 1250 degrees C in a high temperature furnace in ambient air. The polymeric
      binder is pyrolysed during sintering. The resulting scaffolds can be used in
      tissue engineering of bone implants using patient-derived cells that are seeded
      onto the scaffolds. This article describes the process chain, beginning from data
      preparation to 3D printing tests and finally sintering of the scaffold.
      Prototypes were successfully manufactured and characterized. It was demonstrated
      that it is possible to manufacture parts with inner channels with a dimension
      down to 450 microm and wall structures with a thickness down to 330 microm. The
      mechanical strength of dense test parts is up to 22 MPa.

PMID- 15981174
TI  - The role of graft materials in suture augmentation for tendon repairs and
      reattachment.
AB  - Various biomaterials have been used to augment sutures for the repair and
      reattachment of tendons. This study examined four different graft materials in a
      simple and reproducible model using chicken Achilles tendons to determine the
      strength and mechanism of suture reinforcement of tendon repairs. The graft
      materials tested were Gore-Tex(R) Soft Tissue Patch, Graftjacket, bovine
      pericardium, and an experimental graft material from Xylos Corporation. Testing
      was performed in shear to simulate forces on a torn tendon repair and pull-off to
      simulate those on a tendon reattachment to bone. Compared to unaugmented suture,
      grafts increased suture fixation strength from 10% to 60% in shear and from 0% to
      36% in pull-off with the bovine pericardium graft, providing significant
      improvement in both tests. In no cases (even unaugmented) did the suture pull
      directly through the tendon, but instead sliced along it, demonstrating that the
      interface between the suture and the tendon determines fixation strength. Grafts
      function by increasing the area, friction, and nature of this interface, not by
      acting as a barrier for suture pull-through.

PMID- 15981175
TI  - Three-dimensional tomography of composite fracture surfaces.
AB  - The goal of this project was to image the three-dimensional fracture interface of
      a dental composite with the use of X-ray tomography. With the use of the Advanced
      Photon Source (APS) at Argonne National Laboratory, three-dimensional images were
      obtained of the crack interface of a dental composite material that had been
      subjected to three different treatments: a control, cycled in air, and cycled in
      a 50/50 mixture by volume of ethanol and distilled water. The cycle-loaded
      treatments were for 100,000 cycles at a load between 80 and 100 N at 5 Hz. The
      crack interface extended over 28 slices for the control, 96 for the air-cycled
      specimen, and 83 slices for the 50/50 solution cycle specimen. It would appear
      that the fatiguing of the specimens allowed for an increase in the crack
      interface as demonstrated by the 3D tomographical analysis. This volume increase
      in the crack interface is attributed to a separation of the filler fiber from the
      resin matrix. Three-dimensional tomography provides an excellent method to
      observe crack interfaces of dental composites subjected to different types of
      mechanical and environmental conditions.

PMID- 15981176
TI  - Histology and ultrastructure of a tissue-engineered collagen meniscus before and
      after implantation.
AB  - The collagen meniscus implant (CMI) is a tissue-engineering technique designed to
      stimulate regeneration of meniscus-like tissue in cases of irreparable tears or
      previous meniscectomy. CMI morphology was investigated before and after
      implantation by light microscopy, scanning electron microscopy (SEM), and
      transmission electron microscopy (TEM). In a case series biopsy specimens were
      harvested from four patients who underwent a second arthroscopic look 6 months
      after placement of the CMI. CMI sections appeared composed of parallel connective
      laminae of 10-30 microm, connected by smaller bundles (5-10 microm). This
      connective network formed lacunae with diameters between 40 and 60 microm. At
      greater magnification, the walls of the lacunae demonstrated tightly packed and
      randomly distributed collagen fibrils, with diameters ranging from 73 to 439 nm.
      In the biopsy specimens, the lacunae were filled with connective tissue that
      contained newly formed vessels and fibroblast-like cells, presenting an abundant
      rough endoplasmic reticulum and several mitochondria. In the extracellular
      matrix, the collagen fibrils showed uniform diameters (126 nm +/- 32 nm). The
      original structure of CMI was still recognizable, and no inflammatory cells were
      detected within the implant. The morphological findings of this case series
      demonstrate that CMI provides a three-dimensional scaffold suitable for
      colonization by precursor cells and vessels and leading to the formation of a
      fully functional tissue.

PMID- 15981177
TI  - Climate, racial category, and body proportions in the U.S.
AB  - In 1955, Newman and Munro reported correlations between physical characteristics
      and climate in a white male U.S. Army sample. For example, the body weight-to
      mean annual temperature correlation was -0.460. Because the men descended from
      relatively recent immigrants to North America, physical clines implicitly derived
      from differential lifetime growth rather than from natural selection.
      Consequently, both causation and adaptive function of Bergmann's and Allen's
      biogeographic rules in humans were called into question. Analysis of male and
      female data from the 1988 U.S. Army anthropometric survey offers new insights to
      the 1955 study findings. Using state means of the male subsample identifying
      themselves as white, as did Newman and Munro, no significant correlations were
      found between climatic variables and height, weight, BMI, or other body
      proportions. With individual data rather than state mean values, neither white
      male nor white female samples showed morphology to climate correlations.
      Relationships seen in the earlier white sample have disappeared, possibly due to
      a more uniform growth environment and mobility in the U.S. Black males and
      females showed some body trait to climate correlations but only at r values of
      around 0.10. Using state means from the combined sample (racial identification
      ignored), strong correlations are seen. As examples, mean annual temperature
      correlates to male relative sitting height at r = -0.634 and to female relative
      forearm length at r = 0.645. However, these values are evidently spurious, being
      products of the higher percentages of whites enlisting from colder areas of the
      U.S.

PMID- 15981178
TI  - The association between pubertal status and sleep duration and quality among a
      nationally representative sample of U. S. adolescents.
AB  - Many hormones play important roles in both pubertal development and sleep
      regulation. Because of the possible consequences of impaired sleep, including
      impaired health and cognition, it is important to examine whether an association
      between pubertal stage and sleep exists. The aim of this analysis is to examine
      the association between sleep and adolescent growth and developmental stage in a
      large sample of adolescents ages 12-16 years from a nationally representative
      longitudinal study. This analysis used the public-use data set of the National
      Longitudinal Study of Adolescent Health, an extensive survey of health and
      behavior among adolescents in the United States. The study included two
      interviews approximately 1 year apart. Pubertal development, sleep variables, and
      height are self-reported. Pubertal development scores were calculated by summing
      responses to three questions for each sex. The sleep variables include sleep
      duration, frequent insomnia (once/week or more), frequently waking tired
      (once/week or more), and insufficient sleep. The results indicate a sex
      difference in the association between sleep problems and pubertal development.
      Among females, there was a significant increase in sleep problems with increasing
      pubertal development score, but not among males. The negative association between
      sleep duration and pubertal development score, however, was significant in both
      males and females. There is no association between sleep duration and height
      velocity (inches/year) in this sample. The results, which are based on a large
      sample size, warrant further examination with more objective measures into the
      association between sleep and growth and development among adolescents.

PMID- 15981179
TI  - Use of short tandem repeats loci to study the genetic structure of several
      populations from Zulia State, Venezuela.
AB  - Genetic relationships between populations can be studied by comparing genotypic
      and allelic similarities. This investigation aims to demonstrate that selected
      autosomal microsatellite markers could be used to study the genetic structures of
      different populations living in northwest Venezuela, in Zulia State. Seven
      autosomal systems (CSF1PO, TPOX, TH01, vWA, D7S820, D13S317, and D5S818) were
      tested by PCR in a multiplex format on 688 different chromosomes from unrelated
      individuals living in Maracaibo, "Isla de Toas," and "San Jose de Heras," and
      from two Amerindian populations from the "Sierra de Perija," Bari' and Yukpa.
      Allele frequencies, Hardy-Weinberg equilibria, genetic distances, phylogenetic
      trees, and ethnic admixtures were estimated. The study shows the existence of a
      clear genetic difference among these populations in accordance with their
      historic evolution. The populations of Maracaibo and "Isla de Toas" showed a
      triracial origin, with a large European contribution, followed by an Amerindian
      component and a small African component. The indigenous groups, Bari' and Yukpa,
      showed exclusively an Amerindian component, and "San Jose de Heras" showed only
      an African component. These results indicate that microsatellite markers are
      useful for molecular anthropology in a regional and worldwide context and provide
      important genetic information about contemporary populations of Venezuela.

PMID- 15981180
TI  - Variations of somatotype in elderly Sardinians.
AB  - Somatotyping is an effective technique for the study of anthropometric variations
      and body composition in elderly subjects, even though it has not often been used
      in this field. The present study was conducted on a sample of 280 healthy
      Sardinians (134 men and 146 women) of age 60-89 years, subdivided into three age
      classes (60-69 years; 70-79 years; and 80-89 years). Somatotypes were computed
      according to Carter and Heath (Somatotyping-Development and Applications.
      Cambridge, England: Cambridge University Press; 1990). The results show a
      dominance of the endo- and mesomorphic components in the elderly subjects, with
      less development of ectomorphy than in younger individuals. In a comparison with
      other populations, our sample shows strong development of endomorphy and
      especially of mesomorphy, while ectomorphy values are generally low. Age-related
      variations are significant in both sexes and consist in a progressive reduction
      of the endomorphic component, particularly in the 80-89-year class (endomorphy in
      the three age classes: 6.4, 6.1, and 5.3 in men; 8.1, 7.8, and 6.8 in women). The
      mesomorphic component is characterized by stability (age variations: 6.4, 6.4,
      and 5.9 in men; 6.3, 6.4, and 6.3 in women) and the ectomorphic component by a
      slight increase (age variations: 0.5, 0.6, and 0.8 in men; 0.4, 0.3, and 0.5 in
      women). Sex differences are significant and especially large for the endomorphic
      component, with generally higher values in women. The sexual dimorphism tends to
      decrease with age. The results are discussed with regard to the biology of aging,
      with emphasis on the potential application of somatotype to studies of the
      elderly population.

PMID- 15981181
TI  - Catch-up growth or regression to the mean? Recovery from stunting revisited.
AB  - An important question for policy is the extent to which catch-up growth can ease
      the impact of early stunting. Martorell et al. (1992) showed that stunted
      Guatemalan infants remain stunted into adulthood, whereas Adair (1999) found
      appreciable catch-up growth in Filipino children from 2-12 years. Both groups
      defined catch-up as an inverse correlation between early height and subsequent
      growth, but Martorell based the correlation on height, whereas Adair used height
      z scores. The statistical phenomenon of regression to the mean is much like catch
      up growth, an inverse correlation between initial height and later height gain.
      The objective of this study was to reexamine the relationship between stunting
      and later catch-up growth in the context of regression to the mean. The design
      was a theoretical analysis showing that catch-up growth is more evident based on
      height z scores than on height, validated using data on 495 stunted South African
      children seen at 2 and 5 years of age. The correlation between height at 2 and
      height change from 2 to 5 was small based on height (-0.11) but large and highly
      significant based on height z score (-0.58), providing strong evidence of catch
      up growth. We argue that catch-up growth should be estimated using height z score
      not height and that catch-up is present only when the change in z score exceeds
      that predicted by regression to the mean. This leads to a compact definition of
      catch-up growth: if z1 and z2 are the initial and final (mean) height z scores,
      and r is the correlation between them, then catch-up growth for groups or
      individuals is given by (z2 - rz1).

PMID- 15981182
TI  - Does milk make children grow? Relationships between milk consumption and height
      in NHANES 1999-2002.
AB  - In the United States, milk (usually cow's milk) is widely considered an
      "essential food" to support bone growth among post-weaning age children, as
      evident in government-sponsored nutrition policies that mandate milk for
      children. Milk contains calories, protein, and calcium, among other nutrients,
      and bioactive components such as insulin-like growth factor-I (IGF-I), all of
      which may facilitate bone growth. There is a large literature on milk and/or
      calcium intake and its effects on bone density, but one aspect of bone mass-
      height--is not well studied in relation to milk consumption. Limited experimental
      studies show no consistent relationship across populations. To investigate this
      linkage among American children, analysis of the NHANES 1999-2002 was undertaken.
      NHANES data allow two hypotheses to be tested: (1) reported frequency of
      childhood milk consumption will be positively related to adult height and (2)
      height of children 5-18 years will be predicted by the reported frequency of milk
      consumption and/or milk intake from a 24-h dietary recall. Results indicate that
      adult height was positively associated with milk consumption at ages 5-12 and 13
      17, after controlling for sex, education, and ethnicity. Among contemporary
      children, milk consumption had no effect on the height of 5-11 year olds after
      controlling for age, birthweight, energy intake, and ethnicity. In contrast, milk
      consumption frequency and milk intake (measured as grams of milk, or protein or
      calcium from milk) were significant predictors of the height of 12-18 year olds,
      along with age, sex, household income, and ethnicity. The greatest ethnic
      contrasts were between Mexican Americans and non-Hispanic whites and blacks, and
      milk variables remained significant predictors of height in these comparisons.
      Thus NHANES data show substantial variability in the effects of milk consumption
      on height.

PMID- 15981183
TI  - Birth weight among Tibetans at different altitudes in India: are Tibetans better
      protected from IUGR?
AB  - We report the variation in birth weight among the Tibetans at different altitudes
      in India to test the hypothesis of greater protection from intrauterine growth
      retardation (IUGR) among Tibetan compared with other high-altitude native
      populations. We found that the birth weight of Tibetans at Leh (3521 m, high
      altitude) is quite similar to what has been reported previously for Tibetans at
      similar altitudes and is significantly higher than the low-altitude native
      populations living at similar altitudes. Tibetan birth weights are greater than
      those of other ethnic groups, both at high and low altitudes. Compared with
      Tibetans at high altitude (Leh, India; 3521 m), Tibetans at low altitudes
      (Bylakuppe, India; 800 m and Chandragiri, India; 970 m) have heavier birth
      weights. This finding is similar to what has been observed previously for other
      high-altitude native populations. Greater protection from IUGR is not observed
      for Tibetans compared with other high-altitude native populations as was reported
      previously. Genetic potential for birth weight is seemingly manifested only at
      low altitude.

PMID- 15981184
TI  - Cross-population analysis of the growth of long bones and the os coxae of three
      Early Medieval Austrian populations.
AB  - Inter-population variability in long-bone and pelvic-bone growth during the Early
      Medieval period is examined. The materials comprise four archaeological
      populations: two Slavonic (Gars-Thunau, Zwentendorf, Austria, 10th-century AD),
      one Avar (Zwolfaxing, Austria, 8th-century AD), and one Anglo-Saxon (Raunds,
      England, 10th-century AD). Bone measurements are analyzed against dental age
      estimates in order to assess inter-population differences in growth rates for
      long-bone and os coxae bone dimensions. Growth curves of the upper and lower
      extremities of additional archaeological populations and a modern North-American
      population are also assessed. The expectation was that the greatest differences
      in growth patterns would be found between the Anglo-Saxon and the Austrian
      samples, due to their distinct genetic and biocultural background. Minimal
      differences were expected between the two Slavonic populations, as these were
      approximately contemporaneous, recovered from geographically close locations, and
      shared relatively similar archaeological contexts. Growth curves were estimated
      for each bone dimension by fitting least-squares fourth-order polynomials (which
      allowed testing of population differences by analysis of covariance), and
      iteratively estimating Gompertz growth curves. The results showed differences
      between bones in the extent of inter-population variability, with diaphyseal long
      bone growth showing equivalent patterns across the four populations, but
      significant differences between populations in the growth patterns of distal
      diaphyseal dimensions of the femur and humerus and the dimensions of the ilium.
      Varying growth patterns are therefore associated with inter-population
      differences in absolute dimensions in relation to age as well as variations in
      growth velocities. Inter-population variability in growth curves in the case of
      femoral and humeral dimensions were most pronounced during infancy (0-2 years).
      The most consistent differences in bone growth and related dimensions are between
      Zwolfaxing and the other samples. No significant differences in growth were
      detected between the Anglo-Saxon and the Austrian populations.

PMID- 15981185
TI  - Urinary cortisol and muscle mass in Turkana men.
AB  - To determine the role of cortisol in modulating the effects of energetics on
      muscle mass in a subsistence society, measures of cortisol and body composition
      were obtained from a sample of Turkana men. Subjects were 63 settled and 69
      nomadic men, ages 24 and older. Urinary cortisol was determined along with
      measures of muscle mass. Cortisol/creatinine ratio was higher among nomadic men
      (57.8 +/- 56.8 vs. 34.5 +/- 44.6; P < 0.001). Controlled for age, urinary
      cortisol was inversely related to arm muscle plus bone area (MPBA) among the
      nomadic (beta = -0.28; P = 0.04), but not the settled (beta = -0.04; P = 0.78)
      sample. Urinary cortisol was not related to any other measures of body
      composition. These results suggest that even in chronically undernourished
      populations, cortisol may be elevated primarily under conditions of acute
      nutritional stress. However, the catabolic effects of cortisol on muscle in our
      results may be confounded by other energetic factors, including energy
      availability.

PMID- 15981186
TI  - Heterogeneity of the genome ancestry of individuals classified as White in the
      state of Rio Grande do Sul, Brazil.
AB  - One hundred nineteen individuals classified as White, living in different
      localities of the Brazilian state of Rio Grande do Sul, were studied in relation
      to the HVS-I region of the mitochondrial DNA (mtDNA). The male fraction of the
      sample (N = 74) was also tested for seven Y-chromosome polymorphisms. In a
      specific population (Veranopolis), a city characterized by a large influence of
      the Italian immigration of the 19th century, the results from the maternal and
      paternal sides indicated almost complete European ancestry. However, another
      sample identified as White, from different localities of Rio Grande do Sul,
      presented significant fractions of Native American (36%) and African (16%) mtDNA
      haplogroups. These results indicate that Brazilian populations are remarkably
      heterogeneous; while some present an overwhelming majority of transplanted
      European genomes, with a complete correspondence between physical appearance and
      ancestry, others reflect a history of extensive admixture with dissociation
      between physical appearance and ancestry.

PMID- 15981187
TI  - Age-dependent changes of the normal human spine during adulthood.
AB  - The impact of aging on the morphology of the osseous spine is still debated.
      Clinical studies usually record combined aging effects, as well as age-related
      degenerative changes. The aim of this study was to determine the impact of
      (degeneration-independent) aging on the morphology of the osseous human spine
      during adulthood. Various osseous dimensions of human spinal landmarks at all
      major vertebral levels have been assessed in macroscopically normal Swiss
      skeletons (N = 71), with historically known sex and age at death, as well as in
      larger Central European skeletal samples (N = 277) with anthropologically
      determined individual age and sex. All measurements were correlated with
      individual age (or age group) by linear regression and analyzed separately for
      each sex. Only few osseous spinal dimensions, and only in men, correlate
      significantly with individual age. Generally, the significant dimensions show an
      increase in size during adulthood. Similar tendencies, but with significant
      alterations of spinal measurements in women as well, can be found in the larger
      samples with anthropologically determined sex and age group. Increase of certain
      spinal dimensions found in this study may be a reflection of an increase in the
      robustness of individuals with age. Because of the absence of a significant
      secular alteration of stature within the well-recorded sample, we exclude secular
      change in body dimensions as a major bias.

PMID- 15981188
TI  - Fish consumption (hair mercury) and nutritional status of Amazonian Amer-Indian
      children.
AB  - Fish are abundant and important dietary items for the Amer-Indians, and total
      hair-Hg (HHg) concentration is a reliable marker of fish consumption. We studied
      the impact of fish consumption (HHg) on the nutritional status of Indian children
      of Eastern Amazonia. Weight-for-height Z score (WHZ) was measured, and HHg was
      determined in 203 children younger than 10 years of age in three villages. There
      was significantly higher fish consumption in Kayabi children (16.55 microg Hg/g;
      SD, 11.44) than in children of the Munduruku villages of Missao-Cururu (4.76
      microg Hg/g; SD, 2.09) and Kaburua (2.87 microg Hg/g; SD, 2.13). Anthropometric
      indices showed WHZ means of -0.27, -0.22, and 0.40, respectively, for Kayabi,
      Missao-Cururu and Kaburua villages. Despite a different pattern of fish-protein
      consumption between tribes, there was no significant correlation between WHZ and
      HHg concentrations (r2 = 0.0079; P < 0.2021). Dietary differences among Amazonian
      tribes can be traced and used in measuring health outcomes. Higher fish
      consumption, although important for Kayabis, was compensated by other protein
      sources by the Kaburua villagers.

PMID- 15981189
TI  - The preparation and characteristics of a carbonated hydroxyapatite/collagen
      composite at room temperature.
AB  - Nanocarbonated hydroxyapatite/collagen (nCHAC) composite was prepared at room
      temperature via biomimetic self-assembly method. X-ray diffraction (XRD),
      thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) were
      performed. This composite shows the same inorganic phase of natural bone with
      nanosized level and low degree of crystallinity, and contains 2.8-14.7 wt % of
      carbonated content. TEM results confirm that the microstructure of this composite
      is the mineralized collagen fiber bundle like the hierarchical structure of
      natural bone. The diameter of a single mineralized collagen fiber is about 4 nm.
      Slightly different assembly units of the composite with different carbonates and
      collagen were demonstrated. The carbonated percentage affects the mineral crystal
      size and collagen fibril assembly. Because of the biomimetic component and
      microstructure, the use of nCHAC composite is promising for hard tissue therapy.

PMID- 15981190
TI  - Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during
      lung development?
AB  - Congenital diaphragmatic hernia (CDH) usually occurs sporadically. The prognosis
      remains poor, with a 50% perinatal mortality rate. Most deaths result from
      hypoxemia due to lung hypoplasia and abnormal development of pulmonary
      vasculature that results in persistent pulmonary hypertension. Our current
      understanding of the pathogenesis of CDH is based on an assumption linking
      herniation of abdominal viscera into the thorax with compression of the
      developing lung. Pulmonary hypoplasia, however, can also result from reduced
      distension of the developing lung secondary to impaired fetal breathing
      movements. Moreover, a nitrofen-induced CDH model shows that lung hypoplasia
      precedes the diaphragmatic defect, leading to a "dual-hit hypothesis." Recent
      data reveal the role of a retinoid-signaling pathway disruption in the
      pathogenesis of CDH. We describe the clinical and epidemiological aspects of
      human CDH, the metabolic and molecular aspects of the retinoid-signaling pathway,
      and the implications of retinoids in the development of the diaphragm and the
      lung. Finally, we highlight the existing links between CDH and disruption of the
      retinoid-signaling pathway, which may suggest an eventual use of retinoids in the
      treatment of CDH.

PMID- 15981192
TI  - Effect of PbII on the secondary structure and biological activity of trypsin.
AB  - The effects of Pb(II) on the secondary structure and biological activity of
      trypsin have been examined by monitoring changes in its conductivity and IR and
      circular dichroism (CD) spectra. The results show that Pb(II) reacts with
      trypsin, and that the binding sites might be -OH and -NH groups in pepsin. The CD
      spectra indicate that interaction with Pb(II) significantly affects the secondary
      structure of trypsin, the beta-sheet-structure content being increased by about
      42%, whilst those of alpha-helix and beta-turn structures are decreased by 13%
      and 21%, respectively. The results clearly demonstrate that Pb(II) affects the
      biological activity of trypsin by modifying its secondary structure. Most
      interesting is that Pb(II) up-regulates the activity of trypsin at low
      concentrations while down-regulating it at high concentrations.

PMID- 15981193
TI  - Chemical synthesis of a dual branched malto-decaose: a potential substrate for
      alpha-amylases.
AB  - A convergent block strategy for general use in efficient synthesis of complex
      alpha-(1-->4)- and alpha-(1-->6)-malto-oligosaccharides is demonstrated with the
      first chemical synthesis of a malto-oligosaccharide, the decasaccharide 6,6''''
      bis(alpha-maltosyl)-maltohexaose, with two branch points. Using this chemically
      defined branched oligosaccharide as a substrate, the cleavage pattern of seven
      different alpha-amylases were investigated. Alpha-amylases from human saliva,
      porcine pancreas, barley alpha-amylase 2 and recombinant barley alpha-amylase 1
      all hydrolysed the decasaccharide selectively. This resulted in a branched
      hexasaccharide and a branched tetrasaccharide. Alpha-amylases from Asperagillus
      oryzae, Bacillus licheniformis and Bacillus sp. cleaved the decasaccharide at two
      distinct sites, either producing two branched pentasaccharides, or a branched
      hexasaccharide and a branched tetrasaccharide. In addition, the enzymes were
      tested on the single-branched octasaccharide 6-alpha-maltosyl-maltohexaose, which
      was prepared from 6,6''''-bis(alpha-maltosyl)-maltohexaose by treatment with malt
      limit dextrinase. A similar cleavage pattern to that found for the corresponding
      linear malto-oligosaccharide substrate was observed.

PMID- 15981194
TI  - High-throughput evaluation of antioxidant and pro-oxidant activities of
      polyphenols with thymidine protection assays.
AB  - A recently reported high-throughput screening strategy has been applied to the
      rapid selection of new water-soluble antioxidants that display strong protective
      activities. Based on a competitive immunoassay, a triple-screening procedure was
      used to evaluate the ability of different compounds to protect thymidine under
      different oxidative stresses. The pro-oxidant effect of norbadione A in the
      presence of iron was observed, while some pulvinic acid derivatives proved
      strongly protective during gamma radiolysis, UV irradiation, and Fenton-like
      oxidation.

PMID- 15981196
TI  - Transatrial septal catheterization using a new radiofrequency probe.
AB  - Percutaneous therapeutic techniques requiring transseptal catheterization have
      increased in recent years. The traditional and current method for transseptal
      catheterization involves needle puncture, an effective but complicated technique,
      which is associated with a small but significant incidence of both perforation of
      structures adjacent to the atrial septum and pericardial tamponade. Enhanced
      imaging has reduced but not eliminated the risk of these complications. We have
      used an alternative method for transseptal access to the left atrium, which
      employs a novel radiofrequency catheter system. In this report, we describe the
      system and its use in our initial series of patients.

PMID- 15981197
TI  - Polyphenolic profile characterization of Agrimonia eupatoria L. by HPLC with
      different detection devices.
AB  - Liquid chromatography coupled to diode array and electrospray ionization mass
      spectrometry detection was used to establish the polyphenolic profile of an ethyl
      acetate fraction from Agrimonia eupatoria L. aqueous-alcoholic extract.
      Additionally, an HPLC technique with post-column derivatization by p
      dimethylaminocinnamaldehyde was employed for the selective detection and
      quantification of flavan-3-ols. Important information was obtained by combining
      the data of these two HPLC techniques. Flavan-3-ols (catechin and procyanidins
      B1, B2, B3, B6, B7, C1, C2 and epicatechin-epicatechin-catechin), quercetin 3-O
      glucoside, quercetin 3-O-galactoside, kaempferol 3-O-glucoside, kaempferol 3-O
      (6''-O-p-coumaroyl)-glucoside, apigenin 6-C-glucoside and various phenolic acids
      were identified. Antioxidant activity of the Agrimonia eupatoria L. fraction
      containing these compounds was assessed through the 1,1-diphenyl-2
      picrylhydrazyl, trolox equivalent antioxidant capacity and thiobarbituric acid
      reactive substances methods. Significant activity was observed for this fraction,
      where compounds with recognized antiinflammatory properties such as procyanidins,
      kaempferol 3-O-(6''-O-p-coumaroyl)-glucoside and quercetin glycosides were
      identified for the first time. These results are predictive of the beneficial
      effects of this fraction, or some of its compounds, in human health, as possible
      anti-inflammatory drug.

PMID- 15981198
TI  - Identification of linoleic acid free radicals and other breakdown products using
      spin trapping with liquid chromatography-electrospray tandem mass spectrometry.
AB  - Linoleic acid radical products formed by radical reaction (Fenton conditions)
      were trapped using 5,5-dimethyl-1-pyrrolidine-N-oxide (DMPO) and analysed by
      reversed-phase liquid chromatography coupled to electrospray mass spectrometry
      (LC-MS). The linoleic acid radical species detected as DMPO spin adducts
      comprised oxidized linoleic acid and short-chain radical species that resulted
      from the breakdown of carbon and oxygen centred radicals. Based on the m/z
      values, the short-chain products were identified as alkyl and carboxylic acid
      DMPO radical adducts that exhibited different elution times. The ions identified
      as DMPO radical adducts were studied by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The LC-MS/MS spectra of linoleic acid DMPO radical
      adducts exhibited the fragment ion at m/z 114 and/or the loss of neutral molecule
      of 113 Da (DMPO) or 131 Da (DMPO + H2O), indicated to be DMPO adducts. The short
      chain products identified allowed inference of the radical oxidation along the
      linoleic acid chain by abstraction of hydrogen atoms in carbon atoms ranging from
      C-8 to C-14. Other ions containing the fragment ion at m/z 114 in the LC-MS/MS
      spectra were attributed to DMPO adducts of unsaturated aldehydes, hydroxy
      aldehydes and oxocarboxylic acids. The identification of aldehydic products
      formed by radical oxidation of linoleic acid peroxidation products, as short
      chain product DMPO adducts, is a means of identifying lipid peroxidation
      products.

PMID- 15981199
TI  - Molecular cloning, expression of Sox5 and its down-regulation of Dmrt1
      transcription in zebrafish.
AB  - The doublesex and mab-3-related transcription factor 1 (Dmrt1) is the founding
      member of a family of DM domain genes, involved in gonadogenesis. Here we report
      the cloning of zebrafish Sox5 and use real time PCR to show that its expression
      increases while expression of Dmrt1 decreases during embryogenesis.
      Characterization of the proximal promoter of zebrafish Dmrt1 revealed two
      positive and two negative regulatory regions and a Sox5-binding site. Co
      transfection of dmrt1 (with or without the Sox-binding site), driving an EGFP
      reporter and Sox5 showed further that Sox5 bound the Dmrt1 promoter and inhibited
      Dmrt1 expression. This antagonistic partnership between Dmrt1 and Sox5 suggests a
      potential transcriptional regulatory mechanism for Dmrt1 in early embryogenesis.

PMID- 15981200
TI  - Molecular evidence from ascidians for the evolutionary origin of vertebrate
      cranial sensory placodes.
AB  - Cranial sensory placodes are specialised areas of the head ectoderm of vertebrate
      embryos that contribute to the formation of the cranial sense organs and
      associated ganglia. Placodes are often considered a vertebrate innovation, and
      their evolution has been hypothesised as one key adaptation underlying the
      evolution of active predation by primitive vertebrates. Here, we review recent
      molecular evidence pertinent to understanding the evolutionary origin of
      placodes. The development of vertebrate placodes is regulated by numerous genes,
      including members of the Pax, Six, Eya, Fox, Phox, Neurogenin and Pou gene
      families. In the sea squirt Ciona intestinalis (a basal chordate and close
      relative of the vertebrates), orthologues of these genes are deployed in the
      development of the oral and atrial siphons, structures used for filter feeding by
      the sessile adult. Our interpretation of these findings is that vertebrate
      placodes and sea squirt siphon primordia have evolved from the same patches of
      specialised ectoderm present in the common ancestor of the chordates.

PMID- 15981201
TI  - A novel osteotropic biomaterial OG-PLG: Synthesis and in vitro release.
AB  - Statins (e.g., simvastatin) have shown to induce expression of the bone
      morphogenic protein-2 gene in bone cells, but they are not used clinically
      because of a lack of a suitable delivery device. The overall objective is to
      develop optimized statin delivery devices for bone regeneration. The specific
      objective was to determine the effect of grafting statins to biodegradable
      poly[lactide-co-glycolide] (PLG) on release kinetics. Simvastatin was grafted to
      PLG (OG-PLG) and characterized using contact-angle measurements, attenuated total
      reflectance-Fourier transform infrared, and ultraviolet-visible spectroscopy to
      determine success of the synthesis. An ultraviolet-visible assay for measuring
      release of statins and degraded OG-PLG in media was also developed. In vitro
      release studies using films and scaffolds made with PLG, PLG blended with
      simvastatin (PLG + Sim), and OG-PLG (simvastatin grafted to PLG) blended into PLG
      at different concentrations showed that release rate of OG-PLG from films was
      significantly greater than that of PLG + Sim. However, release rate from
      scaffolds showed PLG + Sim to be significantly higher than that of OG-PLG. The
      diffusion-controlled release kinetics of simvastatin from PLG + Sim seems to be
      more heavily affected by device morphology, whereas the degradation-controlled
      release kinetics seem to be less affected. In short, release kinetics can be
      modulated by grafting statins to PLG.

PMID- 15981202
TI  - Major upper gastrointestinal surgery is associated with an antigen-dependent
      proinflammatory T cell response.
AB  - BACKGROUND: T cells play a central role in the immune response to injury.
      Oesophageal and pancreatic resections are associated with significant risk of
      systemic inflammatory response syndrome and sepsis. This study involved a
      detailed analysis of T cell function in a consecutive cohort of patients
      undergoing such surgery. METHODS: Twenty-five patients undergoing major
      oncological upper gastrointestinal surgery were investigated for T cell
      expression of Fas and the activation markers CD69 and CD25, as well as
      interleukin (IL) 2, IL-10 and interferon (IFN) gamma responses to stimulation
      with staphylococcal enterotoxin B (SEB). T cell activation in healthy volunteer
      peripheral blood mononuclear cells was studied in co-culture with patients'
      serum, either alone or with cytotoxic T lymphocyte-associated antigen (CTLA) 4,
      an inhibitor of antigen presentation. RESULTS: T cells expressed significantly
      raised levels of CD69 and CD25 after surgery, but no change in Fas expression was
      evident. There was a significant increase in the production of IL-2 after surgery
      without a concomitant increase in IFN-gamma or IL-10 in response to SEB.
      Postoperative serum activated healthy volunteer T cells, a response that was
      inhibited (P = 0.053) by co-incubation with CTLA-4. CONCLUSION: Major surgery
      results in pan-T cell activation via a serum-mediated antigenic mechanism that is
      independent of Fas expression. Postoperative T cells are primed for an augmented
      proinflammatory response to superantigen, sustained for at least 1 week,
      implicating the adaptive immune system in the development of the postoperative
      systemic immunoinflammatory state.

PMID- 15981203
TI  - Correlation of DNA damage in epidemic dropsy patients to carcinogenic potential
      of argemone oil and isolated sanguinarine alkaloid in mice.
AB  - In recent times, a higher incidence of gall bladder carcinoma in the Indo
      Gangetic basin has been linked with the consumption of contaminated mustard oil.
      Consumption of mustard oil contaminated with argemone oil (AO) is well known to
      cause clinical manifestation referred to as "epidemic dropsy." Because
      sanguinarine, an active alkaloid of AO, has been shown to intercalate DNA, a
      possible correlation of DNA damage in epidemic dropsy patients to tumorigenic
      potential of AO and isolated sanguinarine alkaloid in mice was investigated in
      the present study. Single topical application of AO (0.15-0.3 ml) or isolated
      sanguinarine (4.5-18 micromol) followed by twice-weekly application of
      tetradecanoylphorbolmyristate acetate (TPA) for 25 weeks resulted in formation of
      tumors. Histopathologically these tumors were of squamous cell carcinoma type and
      similar to those found in the positive control group using dimethylbenzanthracene
      (DMBA)/TPA. The activities of cutaneous gamma-glutamyl transpeptidase (GGT) and
      glutathione-S-transferase P (GST-P), marker enzymes of tumorigenesis, were found
      to exhibit higher expression in AO or isolated sanguinarine/TPA treated groups
      when compared to control. The higher expression of p53 and p21/WAF1 in skin after
      single topical application of AO or isolated sanguinarine further confirms the
      tumorigenic response. Single topical application of AO or isolated sanguinarine
      alkaloid to mice showed significant DNA damage in terms of Olive tail moment (89
      129%), tail length (54%) and tail DNA (153-205%) using Comet assay in skin cells.
      Further, the extent of DNA damage in blood cells of epidemic dropsy patients in
      alkaline Comet assay was found to be significantly higher as compared to normal
      population, indicating the genotoxic response of AO exposure. Although the
      genotoxic lesions may be repaired to some extent on withdrawal of consumption of
      AO contaminated mustard oil and the residual genotoxic effects caused by AO may
      not be expressed as signs of carcinogenesis. Environmental factors or hormonal
      changes during aging process may lead to stimulate/promote the genetically
      altered latent cells to form neoplastic lesions and can act as one of the
      etiological factors responsible for higher incidence of gall bladder carcinoma in
      the population of Indo-Gangetic basin.

PMID- 15981205
TI  - RNASEL germline variants are associated with pancreatic cancer.
AB  - The RNASEL (encoding ribonuclease L) gene Glu265X mutation has been implicated in
      familial prostate cancer, and an association between the RNASEL Arg462Gln variant
      and sporadic and familial prostate cancer, has also been suggested. Because
      prostate cancer occurs in some familial pancreatic cancer families, we evaluated
      the role of the RNASEL gene variants Glu265X and Arg462Gln in the etiology of
      pancreatic cancer. Exon 2 of the RNASEL gene was directly sequenced in the
      germline of 36 familial and 75 sporadic pancreatic cancer patients and in 108
      controls. The Glu265X mutation was identified in one (2.8%) familial and one
      (1.3%) sporadic pancreatic cancer case, but not in any of the controls. Arg462Gln
      variants were identified in 61 (56%) controls and in 55 (73%) sporadic pancreatic
      cancer cases with 8 (7%) and 12 (16%) homozygotes, respectively (p = 0.009). For
      homozygous carriers the increased risk for pancreatic cancer was 3.5 (odds ratio
      [OR] = 3.53, 95% confidence interval [CI] = 1.11-11.46, p = 0.03). The population
      attributable fraction (PAF) was 38.7% (95% CI = 0.08-0.80). In familial
      pancreatic cancer no association between Arg462Gln genotypes and pancreatic
      cancer risk was evident. In sporadic pancreatic cancer there were no significant
      differences between Arg462Gln genotypes regarding clinical characteristics. In
      familial pancreatic cancer, however, patients with Arg462Gln variants had more
      aggressive tumors with more high grade cancers (OR = 15.40, p = 0.009) and more
      distant metastases (OR = 7.00, p = 0.04) than patients with the wild-type
      genotype. Our results suggest that RNASEL variants Glu265X and Arg462Gln may
      contribute to the tumorigenesis of sporadic and familial pancreatic cancer, which
      has to be proven in large scale studies.

PMID- 15981204
TI  - Cisplatin activates Akt in small cell lung cancer cells and attenuates apoptosis
      by survivin upregulation.
AB  - The inhibitor of apoptosis protein (IAP) survivin is overexpressed in many tumors
      but is absent in most normal adult tissues. We report high levels of survivin
      expression in small cell lung cancer (SCLC), and describe the role of the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway in survivin upregulation.
      Moreover, the cytoprotective function of survivin in response to the anti-cancer
      agent cisplatin (CDDP) was investigated. Negative modulation of PI3K/Akt using
      pharmacological inhibitors or dominant negative Akt (DN-Akt) decreased Akt kinase
      activity and resulted in decreased survivin expression and phosphorylation on
      Thr34, whereas transfection of constitutively active Akt (CA-Akt) increased
      survivin expression and phosphorylation. Interestingly, we found that treatment
      of SCLC cells with CDDP further increased survivin expression in a cell cycle
      independent manner by activation of Akt. CA-Akt or lentiviral survivin also
      inhibited apoptosis induced by CDDP, whereas DN-Akt or survivin-specific RNA
      interference sensitized cells to CDDP. We identified survivin as an anti
      apoptotic protein in SCLC cells that is regulated by Akt, and demonstrate that
      treatment with the DNA damaging agent CDDP activates the PI3K/Akt/survivin
      pathway that in part protects cells from drug-induced apoptosis.

PMID- 15981206
TI  - Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are
      downregulated in prostate cancer.
AB  - Inactivation of tumor suppressor genes through deletion, mutation and epigenetic
      silencing has been shown to occur in cancer. In our study, we combined DNA
      demethylation and histone deacetylation inhibition treatments with suppression
      subtraction hybridization (SSH) and cDNA microarrays to identify potentially
      epigenetically downregulated genes in PC-3 prostate cancer cell line. We found 11
      genes whose expression was upregulated after relieving epigenetic regulation.
      Expression of 3 genes [dual-specificity phosphatase 1 (DUSP1),
      serum/glucocorticoid regulated kinase (SGK) and spermidine/spermine N1
      acetyltransferase (SAT)] was subsequently studied in clinical sample material
      using real-time quantitative RT-PCR and immunohistochemistry. The DUSP1 and SGK
      mRNA expression was lower in hormone-refractory prostate carcinomas compared to
      benign prostate hyperplasia (BPH) or untreated prostate carcinomas. BPH, normal
      prostate and high-grade prostate intraepithelial neoplasia (PIN) expressed high
      levels of DUSP1 and SGK proteins. Ninety-two percent and 48% of the prostate
      carcinomas showed almost complete lack of DUSP1 and SGK proteins, respectively,
      indicating common downregulation of these genes. The genomic bisulphite
      sequencing did not reveal dense hypermethylation in the promoter regions of
      either DUSP1 or SGK. In conclusion, the data suggest that downregulation of DUSP1
      and SGK is an early event and could be important in the tumorigenesis of prostate
      cancer.

PMID- 15981207
TI  - Differential MHC class II component expression in HPV-positive cervical cancer
      cells: implication for immune surveillance.
AB  - Effective eradication of human papillomavirus (HPV)-positive tumors may require
      CD8+ and CD4+ T-cell-mediated immune responses. Ectopic expression of MHC class
      II surface molecules has been described in the context of cervical cancer, but
      coexpression with other components of the MHC class II antigen presentation
      pathway has not been addressed. We have evaluated the MHC class II antigen
      presentation pathway in malignant squamous epithelium of HPV+ cervical cancer
      lesions by in situ costaining HLA-DR with CLIP or DMA/DMB. Cervical cancer cells
      exhibit 3 MHC class II phenotypes: (i) DR+/CLIP+ or DM+; (ii) DR+/CLIP- or DM-;
      and (iii) DR-/CLIP+ or DM+. The identical profile has been identified in HPV+
      ME180 cells, which serve as a target for HLA-DR4-restricted and HPV68, E7
      specific CD4+ T cells. IFN-gamma pretreatment of ME180 cells, associated with
      differential trafficking of MHC class II molecules, is necessary for effective T
      cell recognition. Although proinflammatory cytokines may facilitate MHC class II
      restricted antigen recognition in tumor cells, different phenotypes of the MHC
      class II antigen presentation pathway may be associated with evasion from CD4+
      mediated cellular immune responses.

PMID- 15981208
TI  - B7-1 and B7-2 act differentially in the induction of a T cell response: their
      impact for a HLA-matched and HLA-mismatched anti-tumor immunotherapy.
AB  - The efficacy of T cell-based immunotherapy is primarily due to efficient cellular
      activation that requires the engagement of 2 separate signals, i.e., via the T
      cell receptor complex and via co-stimulatory molecules the prototype of which is
      CD28. In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are
      thought to play nearly identical roles in T cell activation. We monitored the T
      cell response upon co-culture with HLA Class I-matched and mismatched renal
      carcinoma cells, respectively, that express different levels of B7-1 and B7-2,
      respectively. In a HLA Class I-mismatched co-culture, T cell proliferation, IFN
      gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor
      cells. In contrast, in a HLA Class I-matched situation, B7-2 is more effective in
      the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules
      induce T cell proliferation equally efficient. B7-2 is more effective than B7-1
      in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and
      mismatched situations. The distinct patterns of cytokine induction by B7-1 and B7
      2 obviously depend on the HLA Class I compatibility. These conclusions have
      substantial implications for the development of B7-based vaccines used for
      immunotherapies.

PMID- 15981209
TI  - Alcohol intake in adolescence and mammographic density.
AB  - Adolescent exposures may be important in the development of breast cancer later
      in life. We examined the association of adolescent alcohol consumption and adult
      mammographic density, a strong risk factor for breast cancer. Women within the
      Minnesota Breast Cancer Family Cohort with detailed mammogram and risk factor
      information (n = 1,893) formed our sample. Breast cancer cases were excluded.
      Adolescent alcohol consumption (before age 18) was solicited through a mailed
      questionnaire. Percent density (PD) was estimated using the computer-assisted
      thresholding program, Cumulus. Statistical analyses were performed using linear
      mixed effect models. Women who reported ever drinking alcohol before age 18 (n =
      390; 21%) had a higher unadjusted PD than women who never drank during
      adolescence (mu(unadj) = 26.5% vs. 22.2%), but this difference disappeared with
      adjustment for risk factors for mammographic density (mu(adj) = 21.0% vs. 21.2%,
      p = 0.94). Adult PD was not associated with age at initiation, amount of alcohol
      consumed at one sitting or frequency of alcohol use before age 18. The lack of
      differences was seen across strata of menopausal status. There was suggestion of
      higher PD among heavy and more frequent drinkers (24.0%, 95% CI 21.1-26.8%)
      compared to lighter (21.3%, 95% CI 20.3-22.3%) and never drinkers (21.4%, 95% CI
      20.9-21.9%) and also among regular adolescent drinkers who were daily or weekly
      adult drinkers (25.0%, 95% CI 23.0-27.0%) compared to less regular drinkers in
      these 2 time periods (23.0-23.4%). However, these associations were not
      statistically significant (p = 0.27 and p = 0.22, respectively). In summary,
      there was no evidence that adolescent alcohol use was associated with large and
      persistent effects on adult PD.

PMID- 15981210
TI  - Clinical significance of CXCR3 and CXCR4 expression in primary melanoma.
AB  - Tumor cell migration involved in metastases is a tightly regulated, nonrandom
      process. Chemokines have been identified as critical molecules guiding cell
      migration. We performed a prospective study to analyze a possible association
      between the expression of chemokine receptors CXCR3 and CXCR4 by primary melanoma
      and clinical outcome. Forty primary melanomas were available for analysis; 57% of
      the tumors expressed CXCR3 and 35% expressed CXCR4 by melanoma cells. At initial
      diagnosis, 5 patients had subclinical lymph node involvement and after a median
      follow-up time of 32 months, 2 additional patients developed regional lymph node
      metastases and 5 patients developed distant metastases. The expression of CXCR4,
      but not CXCR3, by melanoma cells in primary lesions was significantly associated
      with the presence of ulceration, increased tumor thickness, a greater risk of
      developing regional and distant metastases and a higher mortality rate. Our study
      underscores the value of CXCR4 expression as a useful marker for predicting
      outcome in patients with localized melanoma. In addition, our findings support
      that, among chemokine receptors, CXCR4 might be an appropriate therapeutic target
      for adjuvant therapy in patients at risk for metastatic disease.

PMID- 15981211
TI  - Risk assessment of p53 genotypes and haplotypes in tobacco-associated leukoplakia
      and oral cancer patients from eastern Idia.
AB  - The role of 3 p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro
      and intron 6 NciI RFLP at np 13494) as potential markers for indicating cancer
      risk remains inconclusive. In our case-control study consisting of 197
      leukoplakia and 310 oral squamous cell carcinoma (SCC) patients and 348 controls,
      genotype frequencies at these 3 p53 loci were determined by PCR-RFLP method and
      analyzed by multiple logistic regression to determine the risks of the diseases.
      The 2/2 genotype at codon 72 of p53 was at risk for developing leukoplakia (OR =
      1.6, 95% CI 1.1-2.3), whereas the combination of 1/2 and 2/2 genotypes at intron
      3 and 1/1 and 1/2 genotypes at intron 6 conferred a protective effect against
      leukoplakia and oral SCC development, respectively (OR = 0.5, 95% CI 0.4-0.8 and
      OR = 0.6, 95% CI 0.5-0.9, respectively). When subjects were stratified according
      to specific tobacco habit, the risk/protection estimates improved significantly
      in some cases. Specifically, the exclusive smokers with p53 codon 72 2/2 genotype
      showed a higher risk of developing leukoplakia (OR = 2.7, 95% CI 1.2-6.3).
      Furthermore, a particular p53 haplotype 1-2-2 was at risk for both tobacco
      associated leukoplakia and oral SCC (OR = 1.5, 95% CI 1.1-1.9 and OR = 1.3, 95%
      CI 1.1-1.7, respectively). Our results show that both specific p53 genotype and
      haplotype can indicate risk of tobacco-associated leukoplakia, but risk of
      development of tobacco-associated oral SCC can be predicted by specific p53
      haplotype only.

PMID- 15981212
TI  - Hyperforin, a bio-active compound of St. John's Wort, is a new inhibitor of
      angiogenesis targeting several key steps of the process.
AB  - Hyperforin, a phloroglucinol derivative found in St. John's wort related mainly
      to its antidepressant effects, has been reported recently to induce apoptosis in
      tumour cells and to inhibit cancer invasion and metastasis. We show that
      hyperforin inhibits angiogenesis in vitro in bovine aortic endothelial cells and
      in vivo in the chorioallantoic membrane assay. In a variety of experimental
      systems representing the sequential events of the angiogenic process, hyperforin
      treatment of endothelial cells resulted in strong inhibitory effects. Hyperforin
      inhibited the growth of endothelial cells in culture. Capillary tube formation on
      Matrigel was abrogated completely by addition of hypeforin at the low micromolar
      range. Hyperforin also exhibited a clear inhibitory effect on the invasive
      capabilities of endothelial cells. Zymographic assays showed that hyperforin
      treatment produced a complete inhibition of urokinase and a remarkable inhibition
      of matrix metalloproteinase 2. Our data indicates that hyperforin is a compound
      that interferes with key events in angiogenesis, confirming the recent and
      growing evidence about a potential role of this compound in cancer and metastasis
      inhibition and making it a promising drug for further evaluation in the treatment
      of angiogenesis-related pathologies.

PMID- 15981213
TI  - Comparison of Surgical Risk Score, POSSUM and p-POSSUM in higher-risk surgical
      patients.
AB  - BACKGROUND: Much current interest is focused on the use of the Physiological and
      Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM)
      and the Portsmouth predictor equation (p-POSSUM) for risk-adjusted surgical
      audit. The Surgical Risk Score (SRS) has been shown to offer an equivalent
      accuracy, but was validated using a cohort that contained a high proportion of
      low-risk patients. The aim of this study was to compare the accuracy of mortality
      prediction using SRS with that of POSSUM and p-POSSUM in a cohort of higher-risk
      patients. METHODS: Some 949 consecutive patients undergoing inpatient surgical
      procedures in a district general hospital under the care of a single surgeon were
      analysed. RESULTS: The observed 30-day mortality rate was 8.4 per cent. Mean
      mortality rates predicted using SRS, POSSUM and p-POSSUM scores were 5.9, 12.6
      and 7.3 per cent respectively. No significant difference was observed in the area
      under the receiver-operator characteristic curves for the three methods.
      CONCLUSION: The SRS accurately predicted mortality in higher-risk surgical
      patients. The accuracy of prediction equalled that of POSSUM and p-POSSUM.

PMID- 15981214
TI  - Identification of steroid derivatives that function as potent antiandrogens.
AB  - We have hypothesized that some steroid derivatives bind to the androgen receptor
      (AR) with very low androgenic activity and therefore potentially function as
      better AR antagonists than clinically used antiandrogens, such as flutamide.
      Indeed, we previously found such a compound, 3beta-acetoxyandrosta-1,5-diene-17
      one ethylene ketal (ADEK), with some estrogenic activity. Here we report the
      identification of 2 additional steroid derivatives, 3beta-hydroxyandrosta-5,16
      diene (HAD) and androsta-1,4-diene-3,17-dione-17-ethylene ketal (OAK), as new
      potent antiandrogens. Like ADEK, HAD and OAK could interrupt androgen binding to
      the AR and suppress both dihydrotestosterone- and androstenediol-induced
      transactivations of wild-type and mutant ARs in prostate cancer cells. These 2
      compounds also inhibited prostate-specific antigen expression in LNCaP as well as
      growth of different AR-positive prostate cancer cell lines stimulated by
      androgen. Significantly, HAD and OAK had only marginal agonist effects, as
      compared to hydroxyflutamide. More importantly, in contrast to ADEK, OAK was
      shown to possess marginal estrogenic activity. These results strengthen our
      hypothesis and suggest that selective steroid derivatives could be potent
      antiandrogenic drugs with less unfavorable effects for the treatment of prostate
      cancer.

PMID- 15981215
TI  - Antibody response to a non-conserved C-terminal part of human histone deacetylase
      3 in colon cancer patients.
AB  - Antibodies to cancer antigens can often be detected in the sera of patients,
      although the mechanism of the underlying humoral immune response is poorly
      understood. Using immunoscreening of tumor-derived cDNA expression libraries
      (SEREX), we identified human histone deacetylase 3 (HDAC3) as serologically
      defined antigen in colon cancer. Closely related HDAC1 and HDAC2 do not elicit
      humoral response in colon cancer patients. We show that the C-terminal region of
      HDAC3 protein lacking the homology to other Class I HDAC contains at least 3
      distinct B-cell epitopes that are recognized by the serum antibodies. HDAC3 in
      combination with other SEREX antigens may become a useful molecular biomarker
      with diagnostic or prognostic value for a subset of colon cancer patients.

PMID- 15981216
TI  - Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty
      liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is consistently associated with features
      of the metabolic syndrome, a condition carrying a high risk of cardiovascular
      events. We measured the vasodilatory response of the brachial artery in response
      to ischemia (a test of endothelial function) (FMV) as well as cardiovascular risk
      profile in 52 NAFLD cases and 28 age- and sex-matched controls. The 10-year risk
      of coronary events was calculated according to the Framingham equation and the
      scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33% +/-
      5.93% in NAFLD versus 12.22% +/- 5.05% in controls (P < .0001), and higher in
      pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%) (P =
      .010). No differences were observed in flow-independent vasodilation (response to
      sublingual nitroglycerin). Percent FMV was negatively associated with insulin
      resistance (homeostasis model assessment) in the whole population (r = -0.243; P
      = .030). In logistic regression analysis, NAFLD was associated with a percent FMV
      in the lower tertile (OR, 6.7; 95% CI, 1.26-36.1), after adjustment for age, sex,
      body mass index, and insulin resistance. Among NAFLD patients, low FMV was
      associated with nonalcoholic steatohepatitis (adjusted OR, 6.8; 95% CI, 1.2
      40.2). The 10-year probability of cardiovascular events was moderately increased
      in NAFLD, and particularly in nonalcoholic steatohepatitis. In conclusion, our
      study provides evidence of endothelial dysfunction and increased risk of
      cardiovascular events in NAFLD. The risk of advanced liver disease is well
      recognized in NAFLD patients, but the large majority of cases might experience
      cardiovascular disease in the long term, indirectly limiting the burden of liver
      failure.

PMID- 15981217
TI  - Involvement of the immune response in the cure of metastatic murine CT-26 colon
      carcinoma by low electric field-enhanced chemotherapy.
AB  - Low electric field cancer treatment-enhanced chemotherapy (LEFCT-EC) is a new
      treatment modality that combines chemotherapeutic agents and low electric field
      stimulation. LEFCT-EC was found to destroy malignant mouse tumors and cause
      massive death of tumor cells. This may enable the immune system cells to
      efficiently recognize and eliminate tumor cells at the primary tumor site and at
      metastatic foci. Mice with 15 mm diameter intracutaneous colon carcinomas (CT-26)
      were injected with BCNU (35 mg/kg), and 2 min later the tumors were exposed to
      low electric fields (intensity 40 V/cm, pulse duration 180 micros, frequency 500
      Hz) for 12 min (LEFCT-EC). We found that treatment with LEFCT-EC achieved
      complete cure of 93% of the animals. In comparison, electric fields alone (13%
      cure), chemotherapy alone (0%), surgery (15%) or a combination of surgery and bis
      chloroethyl-nitrosurea, carmustine (BCNU; 84%) treatments resulted in lower cure
      rates. After treatment and cure with LEFCT-EC, 50% of the cured mice developed
      resistance to a tumor challenge (surgery + BCNU only 15%). Furthermore,
      splenocytes from cured animals protected naive animals from a tumorigenic dose of
      tumor cells. Separation of spleen cells into lymphocyte subpopulations indicated
      a major role for CD4 and CD8 T cells in this protection. FACS analysis revealed
      restoration of normal splenocyte subpopulation proportions impaired by cytotoxic
      chemotherapy. Our results suggest that LEFCT-EC can directly destroy primary
      tumors and facilitate the destruction of metastatic disease by enforcement of
      antitumor immune responses.

PMID- 15981219
TI  - Relationship between Thy-1 expression and cell-cycle distribution in human bone
      marrow hematopoietic progenitors.
AB  - Analysis of the relationship between Thy-1 expression and cell-cycle distribution
      of hematopoietic stem cells (HSCs) showed that freshly isolated Thy-1+ and Thy-1-
      subsets of the CD34highCD38-flt-3-Lin- population were predominantly in G0/G1
      phase and remained essentially quiescent, whereas after 6 days of cytokine
      stimulation, the Thy-1+ subset of the population entered the cycling state while
      the Thy-1- subset again remained quiescent. Expression of Thy-1 antigen resulted
      in a drastic increase in the percentage of cycling cells in CD34highCD38-flt-3
      Lin-Thy-1+- as well as CD34highCD38-flt-3-Lin- Thy-1(-)-cell-initiated cultures.
      The Thy-1+ subset of the CD34highCD38-flt-3-Lin- population exists in the freshly
      isolated CD34highCD38-flt-3-Lin- Thy-1+ fraction, loses Thy-1 expression during 6
      days, and re-expresses Thy-1 for an additional 2 days. Cell-cycle analysis
      demonstrated that this unique subset contains abundant S/G2M cells. Thus, Thy-1
      expression appears to be an indicator of cell-cycle phase in targeting HSC, which
      might serve in the cell subset best suited for gene transfer.

PMID- 15981220
TI  - Megakaryoblastic leukemia with involvement of the pleural fluid.

PMID- 15981221
TI  - Thalidomide-dexamethasone as primary therapy for advanced multiple myeloma.
AB  - The value of thalidomide-dexamethasone was assessed in 26 consecutive, previously
      untreated patients with multiple myeloma of high tumor mass. All showed Hgb < 8.5
      g/dL, serum calcium > 11.5 mg/dL, or both. The response rate was 73%, frequency
      of early death < 3 months was 5%, projected median survival was 30 months, and
      projected median remission time was 25 months. There were no occurrences of grade
      3 or 4 neutropenia or thrombocytopenia, so that serious infection occurred in
      only 12% of patients. Thalidomide-dexamethasone was useful for these patients
      with advanced disease because of the high response rate and acceptable survival,
      with a low frequency of serious complications.

PMID- 15981222
TI  - Flow-cytometric analysis of peripheral blood neutrophils: a simple, objective,
      independent and potentially clinically useful assay to facilitate the diagnosis
      of myelodysplastic syndromes.
AB  - The diagnosis of myelodysplastic syndromes (MDS) is based upon cytopenias,
      morphologic dysplasia, and cytogenetic abnormalities. Because morphologic
      dyspoiesis may be subtle, and many cases have normal cytogenetics, additional
      objective diagnostic tools are needed. We previously developed a novel peripheral
      blood neutrophil flow-cytometric (FCM) scoring system to identify patients with
      MDS. Here, in an analysis of 25 patients, we demonstrate that FCM abnormalities
      are independent of currently measured parameters in MDS, including cytopenias,
      marrow blast percent, and IPSS score. Importantly, FCM abnormalities were seen in
      9/16 MDS patients with normal cytogenetics, suggesting that this simple, non
      invasive assay could play a central role in the diagnosis of MDS.

PMID- 15981223
TI  - Extrapulmonary tuberculous abscess in chronic lymphocytic leukaemia (CLL) treated
      with fludarabine: case report and review of literature.

PMID- 15981224
TI  - Toxicity of argatroban overdose in a 65-year-old man.

PMID- 15981225
TI  - Fibrocongestive splenomegaly in sickle cell disease: a distinct
      clinicopathological entity in the Eastern province of Saudi Arabia.
AB  - Sickle cell disease displays a unique progression in the Eastern province of
      Saudi Arabia, where splenomegaly with hypersplenism is noted with high frequency
      in the adolescent and adult patients. The late persistence of splenomegaly
      although likely reflects the milder progression of sickle cell disease in this
      region; nevertheless, it predisposes the patients to increased morbidity. The
      present study documents the characteristic clinicopathological features of
      splenomegaly associated with sickle cell disease in the Al-Hassa region of
      Eastern province Saudi Arabia. Forty-four cases of sickle cell disease patients
      in whom splenectomy was performed during 1999-2003 were studied. The
      hemoglobinopathy profiles of the patients (age range 5-42 years) comprised sickle
      cell anemia (8 cases), sickle cell anemia with high fetal hemoglobin (23 cases),
      and sickle cell-beta degrees thalassemia (13 cases). All patients had
      manifestations of hypersplenism and 39 patients experienced episodes of minor
      type sequestration crisis. Splenectomy was effective in ameliorating the
      hematological abnormalities in all cases, without any major complications in the
      follow-up period. The splenectomy specimens showed moderate-to-marked enlargement
      in most cases, with histological features of fibrocongestive splenomegaly and
      prominent Gandy-gamma body formations. Micro-infarcts in 27 cases and gross
      infarctions in 9 cases were evident. The relationship of persistent splenomegaly
      with higher fetal hemoglobin levels and splenic hypofunction is examined along
      with the significance of splenectomy in these cases.

PMID- 15981226
TI  - Mini-BEAM and autologous hematopoietic stem-cell transplant for treatment of post
      transplant lymphoproliferative disorders.
AB  - Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of
      lymphoid proliferative diseases seen as result of immunosuppression in recipients
      of solid organ or hematopoietic stem-cell transplantation. Options of treatment
      include reduction or discontinuation of immunosuppressive agents, antiviral
      drugs, rituximab, chemotherapy, and radiation. We report two unique cases of PTLD
      (CNS and plasmacytoma-like) treated successfully with salvage chemotherapy, mini
      BEAM chemotherapy, and autologous stem-cell transplant. In both cases, patients
      were also treated with sirolimus and prednisone as immunosuppression, and neither
      patient rejected their solid organ transplants. With over 30 months of follow-up,
      both patients remain in complete remission with excellent allograft function.

PMID- 15981227
TI  - Venous thromboembolism prevention in the acutely ill medical patient: a review of
      the literature and focus on special patient populations.
AB  - Although venous thromboembolism (VTE) is a major public health problem, until
      recently, our understanding of the risk of VTE in hospitalized acutely ill
      medical patients has been incomplete. Fortunately, over the past 5 years, there
      has been an increasing body of literature that highlights the risk of VTE in the
      nonsurgical patient, identifies unique patient-risk factors, and defines adequate
      preventative measures. This review highlights the current literature with regard
      to epidemiology of VTE in hospitalized medical patients and the risk
      stratification of these patients and deals with optimal preventative regimens and
      prevention strategies in special patient groups.

PMID- 15981228
TI  - Fluid retention during arsenic trioxide treatment in acute promyelocytic
      leukemia.

PMID- 15981229
TI  - Prevalence of elevated antithyroid antibodies and antinuclear antibodies in
      children with immune thrombocytopenic purpura.
AB  - The prevalence and significance of autoantibodies found at the time of diagnosis
      of childhood ITP were studied to correlate their presence with risk for
      development of chronic ITP. Children presenting with acute or chronic ITP to The
      James Whitcomb Riley Hospital for Children between July 1993 and September 1994
      were tested at study entry and followed for the presence of antithyroid
      antibodies (ATA), antinuclear antibodies (ANA), Coombs' reactivity, and anti
      human immunodeficiency virus (HIV) antibodies. Grouped data were evaluated for
      significance using Fisher's exact t-test. Thirty-one patients were enrolled in
      the study with a median age of 8 years (range 17 months-16 years) and male-to
      female ratio of 1:1.8. Forty-two percent of these children had an acute course of
      ITP, and 58% of children had a chronic course of ITP. Of children with acute ITP,
      three (23%) of the patients had an acute nonplatelet autoantibody detected. Of
      the children with chronic ITP, six (33%) of the children had at least one
      abnormal antibody value. Five children (16%) tested positive for ATA: 2 children
      with acute ITP and 3 with chronic ITP. Five children had positive ANA, and of
      these children, 4 (80%) had chronic ITP. Sixty-seven percent of patients testing
      positive for autoantibodies were female, and 67% of all patients were 12 years of
      age or older. Three patients, 1 with acute ITP and 1 with chronic ITP, had
      insignificant abnormal thyroid function tests (these children had minimally
      elevated T3 with otherwise normal thyroid function, and none of these children
      had autoantibodies). No patients included in the study tested positive for HIV.
      Our results suggest that patients with acute ITP who also have other
      autoantibodies may be more likely to develop chronic ITP than those lacking these
      autoantibodies. Larger studies are needed to determine whether the presence of
      ATA or ANA is predictive of clinically significant autoimmune disease.

PMID- 15981230
TI  - Evaluation of single-tube osmotic fragility as a screening test for thalassemia.
AB  - A single-tube osmotic fragility test has been proposed for thalassemia screening
      with a range of different concentrations of saline having been employed. We have
      compared the sensitivity and specificity of 0.32%, 0.34%, and 0.36% buffered
      saline, and on the basis of our findings, recommend the use of 0.36% saline. This
      gave definitely positive or equivocal results in 81 of 85 patients with beta
      thalassemia trait and in 4 of 4 with alpha(0) thalassemia trait. There were 14%
      false positive results in hematologically normal patients and 81% of the samples
      from patients with various variant hemoglobins gave positive results. The
      sensitivity was 95% and specificity 86%. The single-tube osmotic fragility test
      is potentially useful in under-resourced laboratories although it cannot replace
      automated red cell indices using electronic counters.

PMID- 15981231
TI  - Polymorphisms of drug-metabolizing enzymes and risk of childhood acute
      lymphoblastic leukemia.
AB  - The involvement of phase I and II enzymes is well documented in the metabolism of
      a wide range of drugs and xenobiotics. Single-nucleotide polymorphisms (SNPs) of
      these enzymes are also known to alter their protein expression and function.
      Moreover, genetic susceptibility and environmental exposure have been proposed to
      be an etiology of cancer. We hypothesized that polymorphisms of these enzymes
      might affect the risk of childhood acute lymphoblastic leukemia (ALL). CYP 1A1,
      CYP 3A4*1B, CYP 3A5*3, CYP 3A5*6, GSTM1, and GSTT1 polymorphisms were genotyped
      by using PCR-RFLP in 107 children with ALL and 320 healthy controls. Allele and
      genotype frequencies of each of the SNPs were compared between two groups. It was
      found that the allele frequencies of CYP 1A1*1, *2A, *2B, and *4 were not
      different between cases and controls. CYP 3A4*1B allele frequency was only 0.8%
      and 0.9% in ALL and controls, respectively. CYP 3A5*1/*1, *1/*3, and *3/*3
      genotype frequencies showed no statistically significant difference between
      patients and controls. CYP 3A5*6 was not detected in our population. The GSTM1
      null genotype was significantly increased in children with ALL (OR 1.7; 95% CI,
      1.0, 2.7). In contrast, the GSTT1 null genotype did not show this effect. Our
      data thus demonstrate that the GSTM1 null genotype might increase the risk of
      childhood ALL in a Thai population.

PMID- 15981232
TI  - Successful hematopoietic stem-cell transplantation in multicentric Castleman
      disease complicated by POEMS syndrome.
AB  - A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly,
      and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the
      presence of a monoclonal protein. Histological examination of the spleen
      following splenectomy showed multifocal vascular proliferation and angiovascular
      lesions consistent with multicentric Castleman disease. He was treated with
      steroids and rituximab, but without improvement. The patient was found to have
      portal venous thrombosis and lower extremity arterial thrombosis. He then
      received combination chemotherapy with cyclophosphamide and mitoxantrone but
      developed a severe inflammatory polyneuropathy that left him disabled and
      wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS
      syndrome was made, and he then received high-dose chemotherapy with melphalan
      followed by autologous peripheral blood stem-cell transplantation. Following
      transplantation, his nerve conduction studies improved and his serum protein
      electrophoresis normalized. He is currently ambulatory and does not need
      wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment
      option for patients with multicentric Castleman disease and POEMS syndrome.

PMID- 15981233
TI  - Veno-occlusive disease of the liver associated with chronic myelomonocytic
      leukemia treated with vincristine and standard doses of cytarabine.
AB  - A unique case of a 72-year-old man with chronic myelomonocytic leukemia (CMML)
      who developed hepatic veno-occlusive disease (VOD) after treatment with a single
      dose of vincristine and standard doses of cytarabine is described. Unexpected
      peroneal nerve palsy suggestive of vincristine neurotoxicity occurred
      concurrently and pointed to vincristine as the most likely cause of the VOD. To
      the best of our knowledge, association between vincristine and hepatic VOD has
      not been previously described in chemotherapy-naive patients with CMML.

PMID- 15981234
TI  - von Willebrand's disease and menorrhagia: prevalence, diagnosis, and management.
AB  - The reported prevalence of von Willebrand's disease (vWD) is increased in women
      with menorrhagia, with current estimates ranging from 5% to 20%. The consistent
      results of multiple studies suggest testing should be included in the evaluation
      of patients with menorrhagia, especially in unexplained cases and prior to
      surgical intervention. Although a cyclic variation in von Willebrand's factor
      levels has not been confirmed, several studies suggest lower levels during menses
      and the early follicular phase. Menorrhagia is one of the most common bleeding
      manifestations of von Willebrand's disease, reported by 60-95% of women afflicted
      with this bleeding disorder. Menorrhagia is typically severe, often resulting in
      anemia and interfering with quality of life. Despite the frequency of
      menorrhagia, there is no consensus on optimal management. Although oral
      contraceptives are frequently prescribed, there are no studies confirming their
      efficacy using objective measures of response. Desmopressin was associated with
      an 80-92% response rate in several uncontrolled studies relying on patient
      assessment of efficacy. However, a small, randomized trial found no significant
      reduction in menstrual blood flow compared with placebo. There are anecdotal
      reports of the successful use of antifibrinolytic agents alone and in combination
      with other therapies. There are no studies comparing the relative efficacy and
      safety of the available medical therapies for von Willebrand's disease associated
      menorrhagia. Until these studies are completed, treatment should be
      individualized based on von Willebrand's disease subtype, patient age,
      contraceptive needs, and personal preference.

PMID- 15981235
TI  - A relapse of joining.

PMID- 15981236
TI  - Cytogenetic evaluation of a large series of hepatoblastomas: numerical
      abnormalities with recurring aberrations involving 1q12-q21.
AB  - Hepatoblastoma is a malignant embryonal liver tumor that occurs almost
      exclusively in infants and very young children. Previous cytogenetic studies of
      hepatoblastoma have investigated small series or individual cases. This report is
      on the cytogenetics of a large series of 111 hepatoblastoma specimens, with
      cytogenetic results consecutively karyotyped over a 12-year period. Abnormal
      karyotypes were observed in 55 cases (approximately 50% of the total). Numerical
      aberrations were observed in 41 cases (36% of the total), particularly trisomies
      of chromosomes 2, 8, and 20. Chromosome losses were less common than chromosome
      gains. Structural abnormalities were observed in 43 cases (39% of the total).
      Unbalanced translocations resulting in trisomy 1q and involving breakpoints at
      1q12-21 were the most common structural abnormality, observed in 20 tumors (18%
      of total cases); the corresponding translocated chromosome was highly varied. The
      previously reported t(1;4) was observed in seven cases. Most tumors with
      translocations involving 1q12-21 also displayed numerical chromosome aberrations,
      the most common of which were chromosomal trisomies, whereas tumors with other
      structural rearrangements had fewer numerical abnormalities.

PMID- 15981238
TI  - The critical impact of Frantz Fanon and Henri Collomb: race, gender, and
      personality testing of North and West Africans.
AB  - In 2001, the U.S. Surgeon General declared publicly that culture counts in mental
      health care. This welcome recognition of the role of culture in mental health
      appears somewhat belated. In 1956, Frantz Fanon and Henri Collomb both presented
      culturally sensitive studies of the Thematic Apperception Test at the major
      French-language mental health conference. The contrast between these two studies
      and between the careers of Fanon and Collomb reveals some of the difficulties in
      creating cultural and gender sensitivity in psychiatry or psychology.

PMID- 15981239
TI  - The Sociological Department at the Colorado Fuel and Iron Company, 1901 to 1907:
      scientific paternalism and industrial control.
AB  - The Colorado Fuel and Iron Company's Sociological Department represented an
      industrial welfare plan based on an early understanding of applied sociology. The
      Department was created as a response to the demands of integrating coal and coke
      production with steel manufacturing, and the necessity of combating strikes among
      the immigrant workers. The "settlement house model" used by the Sociological
      Department was intended to foster labor stability by transforming the lifestyles
      and habits of the immigrant workers and their families. It is concluded that the
      industrial welfare programs that were intended to inspire loyalty to the company
      merely added to the workers' grievances with the company.

PMID- 15981241
TI  - Strategic self-marginalization: the case of psychoanalysis.
AB  - Marginality is an important concept in the history of science, though it is often
      used in a manner that presumes marginality to be a static designation. We contend
      that the dynamics of marginality are crucial to the history of psychoanalysis, a
      discipline that has moved between dominant and marginal positions. We address
      psychoanalytic marginality via three specific "cases": the marginalization among
      Freud and his followers when psychoanalysis was an emergent discipline; the
      marginality trope in Erich Fromm's popular psychoanalytic writing when
      psychoanalysis was orthodoxy in American academic psychiatry; and the rhetorical
      marginality of psychoanalysis in Sweden as psychoanalysis entered a decline
      within psychiatry. Our aim is to show that marginalization and self
      marginalization serve interpersonal, social, and professional strategies.

PMID- 15981242
TI  - DSM-III and the revolution in the classification of mental illness.
AB  - A revolution occurred within the psychiatric profession in the early 1980s that
      rapidly transformed the theory and practice of mental health in the United
      States. In a very short period of time, mental illnesses were transformed from
      broad, etiologically defined entities that were continuous with normality to
      symptom-based, categorical diseases. The third edition of the American
      Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders
      (DSM-III) was responsible for this change. The paradigm shift in mental health
      diagnosis in the DSM-III was neither a product of growing scientific knowledge
      nor of increasing medicalization. Instead, its symptom-based diagnoses reflect a
      growing standardization of psychiatric diagnoses. This standardization was the
      product of many factors, including: (1) professional politics within the mental
      health community, (2) increased government involvement in mental health research
      and policymaking, (3) mounting pressure on psychiatrists from health insurers to
      demonstrate the effectiveness of their practices, and (4) the necessity of
      pharmaceutical companies to market their products to treat specific diseases.
      This article endeavors to explain the origins of DSM-III, the political struggles
      that generated it, and its long-term consequences for clinical diagnosis and
      treatment of mental disorders in the United States.

PMID- 15981243
TI  - Identification and analysis of 21 novel disease-causing amino acid substitutions
      in the conserved part of ATP7A.
AB  - ATP7A encodes a copper-translocating ATPase that belongs to the large family of P
      type ATPases. Eight conserved regions define the core of the P-type ATPase
      superfamily. We report here the identification of 21 novel missense mutations in
      the conserved part of ATP7A that encodes the residues p.V842-p.S1404. Using the
      coordinates of X-ray crystal structures of the sarcoplasmic reticulum Ca(2+)
      ATPase, as determined in the presence and absence of Ca(2+), we created
      structural homology models of ATP7A. By mapping the substituted residues onto the
      models, we found that these residues are more clustered three-dimensionally than
      expected from the primary sequence. The location of the substituted residues in
      conserved regions supports the functional similarities between the two types of P
      type ATPases. An immunofluorescence analysis of Menkes fibroblasts suggested that
      the localization of a large number of the mutated ATP7A protein variants was
      correct. In the absence of copper, they were located in perinuclear regions of
      the cells, just like the wild type. However, two of the mutated ATP7A variants
      showed only partly correct localization, and in five cultures no ATP7A protein
      could be detected. These findings suggest that although a disease-causing
      mutation may indicate a functional significance of the affected residue, this is
      not always the case.

PMID- 15981244
TI  - Complexity of the genotype-phenotype correlation in familial exudative
      vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.
AB  - Familial exudative vitreoretinopathy (FEVR) is a hereditary blinding disorder
      that features defects in retinal vascular development. The mutations in the genes
      encoding the Wnt receptor pair, frizzled 4 (FZD4) and low-density-lipoprotein
      receptor-related protein 5 (LRP5), have been shown to cause FEVR. In this study
      we screened 56 unrelated patients with FEVR (31 familial and 25 simplex cases)
      for possible mutations in LRP5 and FZD4. Six novel mutations in either LRP5 or
      FZD4 were identified in six familial cases. Four novel mutations in LRP5 and one
      known mutation in FZD4 were detected in three simplex cases, and two of these
      patients carried compound heterozygous mutations in LRP5. Remarkably, c.1330C>T
      [p.R444C] in LRP5 was found in the family in which c.1250G>A [p.R417Q] in FZD4
      had previously been identified. The phenotype of these patients suggested a
      synergistic effect of the two mutations in the independent FEVR-causing genes. We
      also demonstrated that reduced bone density is a common feature in patients with
      FEVR who harbor LRP5 mutations. The profile of the mutations obtained in the
      current study further illustrates the complexity of the disease and provides a
      better understanding of the spectrum, frequencies, and genotype-phenotype
      correlation.

PMID- 15981245
TI  - Searching for protein-protein interaction sites and docking by the methods of
      molecular dynamics, grid scoring, and the pairwise interaction potential of amino
      acid residues.
AB  - In CAPRI Rounds 1 and 2, we assumed that because there are many ionic charges
      that weaken electrostatic interaction forces in living cells, the hydrophobic
      interaction force might be important entropically. As a result of Rounds 1 and 2,
      the predictions for binding sites and geometric centers were acceptable, but
      those of the binding axes were poor, because only the largest benzene cluster was
      used for generating the initial docking structures. These were generated by
      fitting of benzene clusters formed on the surface of receptor and ligand. In
      CAPRI Rounds 3-5, the grid-scoring sum on the protein-protein interaction surface
      and the pairwise potential of the amino acid residues, which were indicated as
      coming easily into the protein-protein interaction regions, were used as the
      calculation methods, along with the smaller benzene clusters that participated in
      benzene cluster fitting. Good predicted models were obtained for Targets 11 and
      12. When the modeled receptor proteins were superimposed on the experimental
      structures, the smallest ligand root-mean-square deviation (RMSD) values
      corresponding to the RMSD between the model and experimental structures were 6.2
      A and 7.3 A, respectively.

PMID- 15981246
TI  - Progress in computation and amide hydrogen exchange for prediction of protein
      protein complexes.
AB  - The macromolecular docking problem that must be solved for experimental
      biologists is prediction of the structures of complexes for which the components
      are known or reliably modeled in the unbound state, but the structure of the
      complex is unknown. The current state of the art in macromolecular docking is
      such that solving this problem usually requires supplementary experimental
      chemical and/or biological information to evaluate computational predictions.
      Amide (1)H/(2)H exchange measured by mass spectroscopy is a promising approach
      for obtaining such information, because it can reveal interfacial regions of each
      member of the complex and identify regions of conformational flexibility in the
      structure. In a previous article (Anand et al., Proc Natl Acad Sci USA
      2003;100:13264-13269), we used (1)H/(2)H exchange data to predict the structure
      of a complex between regulatory and catalytic subunits of protein kinase A.
      Comparison of the prediction with a recent crystal structure determination (Kim
      et al., Science 2005;307:690-696) showed large conformational change in the
      regulatory subunit on formation of the complex. Analysis of the prediction,
      previous CAPRI results, novel data processing methods for the (1)H/(2)H exchange
      data, and new fragment docking computations give grounds for cautious optimism
      that this method can be useful even in cases of substantial conformational
      change.

PMID- 15981247
TI  - Sailing the route from Gaeta, Italy, to CAPRI.

PMID- 15981248
TI  - Classification of protein complexes based on docking difficulty.
AB  - Based on the results of several groups using different docking methods, the key
      properties that determine the expected success rate in protein-protein docking
      calculations are measures of conformational change, interface area, and
      hydrophobicity. A classification of protein complexes in terms of these measures
      provides a prediction of docking difficulty. This classification is used to study
      the targets of the CAPRI docking experiment. Results show that targets with a
      moderate expected difficulty were indeed predicted well by a number of groups,
      whereas the use of additional a priori information was necessary to obtain good
      results for some very difficult targets. The analysis indicates that CAPRI and
      other relatively large-scale docking studies represent very important steps
      toward understanding the capabilities and limitations of current protein-protein
      docking methods.

PMID- 15981249
TI  - Progress in protein-protein docking: atomic resolution predictions in the CAPRI
      experiment using RosettaDock with an improved treatment of side-chain
      flexibility.
AB  - RosettaDock uses real-space Monte Carlo minimization (MCM) on both rigid-body and
      side-chain degrees of freedom to identify the lowest free energy docked
      arrangement of 2 protein structures. An improved version of the method that uses
      gradient-based minimization for off-rotamer side-chain optimization and includes
      information from unbound structures was used to create predictions for Rounds 4
      and 5 of CAPRI. First, large numbers of independent MCM trajectories were carried
      out and the lowest free energy docked configurations identified. Second, new
      trajectories were started from these lowest energy structures to thoroughly
      sample the surrounding conformation space, and the lowest energy configurations
      were submitted as predictions. For all cases in which there were no significant
      backbone conformational changes, a small number of very low-energy configurations
      were identified in the first, global search and subsequently found to be close to
      the center of the basin of attraction in the free energy landscape in the second,
      local search. Following the release of the experimental coordinates, it was found
      that the centers of these free energy minima were remarkably close to the native
      structures in not only the rigid-body orientation but also the detailed
      conformations of the side-chains. Out of 8 targets, the lowest energy models had
      interface root-mean-square deviations (RMSDs) less than 1.1 A from the correct
      structures for 6 targets, and interface RMSDs less than 0.4 A for 3 targets. The
      predictions were top submissions to CAPRI for Targets 11, 12, 14, 15, and 19. The
      close correspondence of the lowest free energy structures found in our searches
      to the experimental structures suggests that our free energy function is a
      reasonable representation of the physical chemistry, and that the real space
      search with full side-chain flexibility to some extent solves the protein-protein
      docking problem in the absence of significant backbone conformational changes. On
      the other hand, the approach fails when there are significant backbone
      conformational changes as the steric complementarity of the 2 proteins cannot be
      modeled without incorporating backbone flexibility, and this is the major goal of
      our current work.

PMID- 15981250
TI  - Modeling oligomers with Cn or Dn symmetry: application to CAPRI target 10.
AB  - The abundance of oligomeric proteins makes them a frequent target for structure
      prediction. However, homologous proteins sometimes adopt different
      oligomerization states, rendering the prediction of structures of whole oligomers
      beyond the scope of comparative modeling. This obstacle can be overcome by
      combining comparative modeling of the single subunit of an oligomer with docking
      techniques, designed for predicting subunit-subunit interfaces. We present here
      algorithms for predicting the structures of homo-oligomers with C(n) or D(n) (n >
      2) symmetry. The prediction procedure includes a symmetry-restricted docking step
      followed by a C(n) or D(n) oligomer-forming step, in which the dimers from the
      docking step are assembled to oligomers. The procedure is applied to each of the
      crystallographically independent subunits in 8 C(n) and 3 D(n) oligomers,
      producing very accurate predictions. It is further applied to a single monomer of
      the tick-borne encephalitis virus coat protein E (Target 10 of the CAPRI
      experiment). The predicted trimer ranked 30, obtained via rigid-body geometric
      hydrophobic docking followed by C(n) oligomer formation, is very similar to the
      experimentally observed trimer formed by domain II of this protein. Furthermore,
      the predicted trimer formed from the separated domain I is also close to the
      experimental structure.

PMID- 15981251
TI  - Approaching the CAPRI challenge with an efficient geometry-based docking.
AB  - The last 3 rounds (3-5) of CAPRI included a wide range of docking targets.
      Several targets were especially challenging, since they involved large-scale
      movements and symmetric rearrangement, while others were based on homology
      models. We have approached the targets with a variety of geometry-based docking
      algorithms that include rigid docking, symmetric docking, and flexible docking
      with symmetry constraints. For all but 1 docking target, we were able to submit
      at least 1 acceptable quality prediction. Here, we detail for each target the
      prediction methods used and the specific biological data employed, and supply a
      retrospective analysis of the results. We highlight the advantages of our
      techniques, which efficiently exploit the geometric shape complementarity
      properties of the interaction. These enable them to run only few minutes on a
      standard PC even for flexible docking, thus proving their scalability toward
      computational genomic scale experiments. We also outline the major required
      enhancements, such as the introduction of side-chain position refinement and the
      introduction of flexibility for both docking partners.

PMID- 15981252
TI  - Data-driven docking: HADDOCK's adventures in CAPRI.
AB  - We have shown previously that given high-resolution structures of the unbound
      molecules, structure determination of protein complexes is possible by including
      biochemical and/or biophysical data as highly ambiguous distance restraints in a
      docking approach. We applied this method, implemented in the HADDOCK (High
      Ambiguity Driven DOCKing) package (Dominguez et al., J Am Chem Soc 2003;125:1731
      1737), to the targets in the fourth and fifth rounds of CAPRI. Here we describe
      our results and analyze them in detail. Special attention is given to the role of
      flexibility in our docking method and the way in which this improves the docking
      results. We describe extensions to our approach that were developed as a direct
      result of our participation in CAPRI. In addition to experimental information, we
      also included interface residue predictions from PPISP (Protein-Protein
      Interaction Site Predictor; Zhou and Shan, Proteins 2001;44:336-343), a neural
      network method. Using HADDOCK we were able to generate acceptable structures for
      6 of the 8 targets, and to submit at least 1 acceptable structure for 5 of them.
      Of these 5 submissions, 3 were of medium quality (Targets 10, 11, and 15) and 2
      of high quality (Targets 13 and 14). In all cases, predictions were obtained
      containing at least 40% of the correct epitope at the interface for both ligand
      and receptor simultaneously.

PMID- 15981253
TI  - Modeling side-chains using molecular dynamics improve recognition of binding
      region in CAPRI targets.
AB  - The CAPRI-II experiment added an extra level of complexity to the problem of
      predicting protein-protein interactions by including 5 targets for which
      participants had to build or complete the 3-dimensional (3D) structure of either
      the receptor or ligand based on the structure of a close homolog. In this
      article, we describe how modeling key side-chains using molecular dynamics (MD)
      in explicit solvent improved the recognition of the binding region of a free
      energy- based computational docking method. In particular, we show that MD is
      able to predict with relatively high accuracy the rotamer conformation of the
      anchor side-chains important for molecular recognition as suggested by Rajamani
      et al. (Proc Natl Acad Sci USA 2004;101:11287-11292). As expected, the
      conformations are some of the most common rotamers for the given residue, while
      latch side-chains that undergo induced fit upon binding are forced into less
      common conformations. Using these models as starting conformations in conjunction
      with the rigid-body docking server ClusPro and the flexible docking algorithm
      SmoothDock, we produced valuable predictions for 6 of the 9 targets in CAPRI-II,
      missing only the 3 targets that underwent significant structural rearrangements
      upon binding. We also show that our free energy- based scoring function,
      consisting of the sum of van der Waals, Coulombic electrostatic with a distance
      dependent dielectric, and desolvation free energy successfully discriminates the
      nativelike conformation of our submitted predictions. The latter emphasizes the
      critical role that thermodynamics plays on our methodology, and validates the
      generality of the algorithm to predict protein interactions.

PMID- 15981254
TI  - Study of protein-protein interaction using conformational space annealing.
AB  - We apply conformational space annealing (CSA), an efficient global optimization
      method, to the study of protein-protein interaction. The CSA is incorporated into
      the Tinker molecular modeling package along with a B-spline method for CAPRI
      Round 5 experiments. We have used an energy function for the protein-protein
      interaction that consists of electrostatic interaction, van der Waals
      interaction, and solvation energy terms represented by the occupancy desolvation
      method. The parameters of the AMBER94 all-atom empirical force field are used.
      Each energy term is calculated by precalculated grid potentials and B-spline
      method approximation. The ligand protein is placed inside a sphere of 50 A radius
      centered at an appropriate location, and the CSA rigid docking studies are
      carried out to find stable complexes. Up to 10 complexes are selected using the K
      mean clustering method and biological information when available. These complexes
      are energy-minimized for further refinement by considering the flexibility of
      interacting proteins. The results show that the CSA method has a potential for
      the study of protein-protein interaction.

PMID- 15981255
TI  - Docking prediction using biological information, ZDOCK sampling technique, and
      clustering guided by the DFIRE statistical energy function.
AB  - We entered the CAPRI experiment during the middle of Round 4 and have submitted
      predictions for all 6 targets released since then. We used the following
      procedures for docking prediction: (1) the identification of possible binding
      region(s) of a target based on known biological information, (2) rigid-body
      sampling around the binding region(s) by using the docking program ZDOCK, (3)
      ranking of the sampled complex conformations by employing the DFIRE-based
      statistical energy function, (4) clustering based on pairwise root-mean-square
      distance and the DFIRE energy, and (5) manual inspection and relaxation of the
      side-chain conformations of the top-ranked structures by geometric constraint.
      Reasonable predictions were made for 4 of the 6 targets. The best fraction of
      native contacts within the top 10 models are 89.1% for Target 12, 54.3% for
      Target 13, 29.3% for Target 14, and 94.1% for Target 18. The origin of successes
      and failures is discussed. .

PMID- 15981256
TI  - Energetic and topological analyses of the oxidation reaction between Mo(n) (n =
      1, 2) and N2O.
AB  - The interaction between molybdenum, atom, and dimer, with nitrous oxide has been
      investigated using density functional theory. The analysis of the potential
      energy surfaces for both reactions has revealed that a single molybdenum atom can
      activate the N--O bond of N2O requiring a small activation energy. However, the
      presence of several intersystem crossings between three different spin states,
      namely, septet, quintet and triplet states, seems to be the major constraint to
      the Mo + N2O reaction. Contrarily, the low-lying excited states (triplet and
      quintet) do not participate in the reaction between the molybdenum dimer and N2O.
      The latter reaction fully evolves on the singlet spin surface. Three different
      regions have been distinguished along the pathway: formation of an adduct
      complex, formation of an inserted compound, and the N2 detachment. The connection
      between the two first regions has been characterized by the formation of a
      special complex in which the N--O bond is so weakened that it could be considered
      as a first step in the insertion process. It has been shown that the topological
      changes along the pathways provide a clear explanation for the geometrical
      changes that occur along the reaction pathway. In summary, the detachment of the
      N2 molecule is found to be kinetically an effective process for both reactions,
      owing to the high exothermicity and consequently to the high internal energy of
      the insertion intermediates. However, in the case of Mo atom, the reaction should
      be a slow process due to the presence of spin-forbidden transitions. These
      results fully agree with previous experimental works.

PMID- 15981257
TI  - Absolute free energies of binding of peptide analogs to the HIV-1 protease from
      molecular dynamics simulations.
AB  - The constants of binding of five peptide analogs to the active site of the HIV-1
      aspartic-protease are calculated based on a novel sampling scheme that is
      efficient and does not introduce any approximations in addition to the energy
      function used to describe the system. The results agree with experiments. The
      squared correlation coefficient of the calculated vs. the measured values is
      0.79. The sampling scheme consists of a series of molecular dynamics integrations
      with biases. The biases are selected based on an estimate of the probability
      density function of the system in a way to explore the conformational space and
      to reduce the statistical error in the calculated binding constants. The
      molecular dynamics integrations are done with a vacuum potential using a short
      cutoff scheme. To estimate the probability density of the simulated system, the
      results of the molecular dynamics integrations are combined using an extension of
      the weighted histogram analysis method (C. Bartels, Chem. Phys. Letters 331
      (2000) 446-454). The probability density of the solvated ligand-protein system is
      obtained by applying a correction for the use of the short cutoffs in the
      simulations and by taking into account solvation with an electrostatic term and a
      hydrophobic term. The electrostatic part of the solvation is determined by finite
      difference Poisson-Boltzmann calculations; the hydrophobic part of the solvation
      is set proportional to the solvent accessible surface area. Setting the
      hydrophobic surface tension parameter equal to 8 mol(-1) K(-1) A(-2), absolute
      binding constants are in the muM to nM range. This is in agreement with
      experiments. The standard errors determined from eight repeated binding constant
      determinations are a factor of 14 to 411. A single determination of a binding
      constant is done with 499700 steps of molecular dynamics integration and 4500
      finite difference Poisson-Boltzmann calculations. The simulations can be analyzed
      with respect to conformational changes of the active site of the HIV-1 protease
      or the ligands upon binding and provide information that complements experiments
      and can be used in the drug development process.

PMID- 15981258
TI  - Incorporation of flexibility into rigid-body docking: applications in rounds 3-5
      of CAPRI.
AB  - We have submitted models for all 9 targets in Rounds 3-5 of CAPRI and have
      predicted at least 30% of the correct contacts for 4 of the targets and at least
      10% of the correct contacts for another 4 targets. We have employed a variety of
      techniques but have had the greatest success by combining established rigid-body
      docking with a variety of initial conformations generated by molecular dynamics.

PMID- 15981259
TI  - Development and testing of an automated approach to protein docking.
AB  - A new version of GRAMM was applied to Targets 14, 18, and 19 in CAPRI Round 5.
      The predictions were generated without manual intervention. Ten top-ranked
      matches for each target were submitted. The docking was performed by a rigid-body
      procedure with a smoothed potential function to accommodate conformational
      changes. The first stage was a global search on a fine grid with a projection of
      a smoothed Lennard-Jones potential. The top predictions from the first stage were
      subjected to the conjugate gradient minimization with the same smoothed
      potential. The resulting local minima were reranked according to the weighted sum
      of Lennard-Jones potential, pairwise residue-residue statistical preferences,
      cluster occupancy, and the degree of the evolutionary conservation of the
      predicted interface. For Targets 14 and 18, the conformation of the complex was
      predicted with root-mean-square deviation (RMSD) of the ligand interface atoms
      0.68 A and 1.88 A correspondingly. For Target 19, the interface areas on both
      proteins were correctly predicted. The performance of the procedure was also
      analyzed on the benchmark of bound-unbound protein complexes. The results show
      that, on average, conformations of only 3 side-chains need to be optimized during
      docking of unbound structures before the backbone changes become a limiting
      factor. The GRAMM-X docking server is available for public use at
      http://www.bioinformatics.ku.edu.

PMID- 15981260
TI  - Biologically enhanced sampling geometric docking and backbone flexibility
      treatment with multiconformational superposition.
AB  - An efficient biologically enhanced sampling geometric docking method is presented
      based on the FTDock algorithm to predict the protein-protein binding modes. The
      active site data from different sources, such as biochemical and biophysical
      experiments or theoretical analyses of sequence data, can be incorporated in the
      rotation-translation scan. When discretizing a protein onto a 3-dimensional (3D)
      grid, a zero value is given to grid points outside a sphere centered on the
      geometric center of specified residues. In this way, docking solutions are biased
      toward modes where the interface region is inside the sphere. We also adopt a
      multiconformational superposition scheme to represent backbone flexibility in the
      proteins. When these procedures were applied to the targets of CAPRI, a larger
      number of hits and smaller ligand root-mean-square deviations (RMSDs) were
      obtained at the conformational search stage in all cases, and especially Target
      19. With Target 18, only 1 near-native structure was retained by the biologically
      enhanced sampling geometric docking method, but this number increased to 53 and
      the least ligand RMSD decreased from 8.1 A to 2.9 A after performing
      multiconformational superposition. These results were obtained after the CAPRI
      prediction deadlines.

PMID- 15981261
TI  - Assessment of CAPRI predictions in rounds 3-5 shows progress in docking
      procedures.
AB  - The current status of docking procedures for predicting protein-protein
      interactions starting from their three-dimensional (3D) structure is reassessed
      by evaluating blind predictions, performed during 2003-2004 as part of Rounds 3-5
      of the community-wide experiment on Critical Assessment of PRedicted Interactions
      (CAPRI). Ten newly determined structures of protein-protein complexes were used
      as targets for these rounds. They comprised 2 enzyme-inhibitor complexes, 2
      antigen-antibody complexes, 2 complexes involved in cellular signaling, 2 homo
      oligomers, and a complex between 2 components of the bacterial cellulosome. For
      most targets, the predictors were given the experimental structures of 1 unbound
      and 1 bound component, with the latter in a random orientation. For some, the
      structure of the free component was derived from that of a related protein,
      requiring the use of homology modeling. In some of the targets, significant
      differences in conformation were displayed between the bound and unbound
      components, representing a major challenge for the docking procedures. For 1
      target, predictions could not go to completion. In total, 1866 predictions
      submitted by 30 groups were evaluated. Over one-third of these groups applied
      completely novel docking algorithms and scoring functions, with several of them
      specifically addressing the challenge of dealing with side-chain and backbone
      flexibility. The quality of the predicted interactions was evaluated by
      comparison to the experimental structures of the targets, made available for the
      evaluation, using the well-agreed-upon criteria used previously. Twenty-four
      groups, which for the first time included an automatic Web server, produced
      predictions ranking from acceptable to highly accurate for all targets, including
      those where the structures of the bound and unbound forms differed substantially.
      These results and a brief survey of the methods used by participants of CAPRI
      Rounds 3-5 suggest that genuine progress in the performance of docking methods is
      being achieved, with CAPRI acting as the catalyst.

PMID- 15981262
TI  - CAPRI rounds 3-5 reveal promising successes and future challenges for
      RosettaDock.
AB  - CAPRI Rounds 3, 4, and 5 are the first public test of the published RosettaDock
      algorithm. The targets cover a wide range of sizes and shapes. For most targets,
      published biological information indicated the region of the binding site on at
      least one docking partner. The RosettaDock algorithm produced high accuracy
      predictions for three targets, medium-accuracy predictions for two targets, and
      an acceptable prediction for one target. RosettaDock predicted all five targets
      with less than 450 residues to high or medium accuracy, but it predicted only one
      of seven targets with above 450 residues to acceptable accuracy. RosettaDock's
      high-accuracy predictions for small to moderately large targets reveal the
      predictive power and fidelity of the algorithm, especially the high-resolution
      refinement and scoring protocol. In addition, RosettaDock can predict complexes
      from at least one homology-modeled docking partner with comparable accuracy to
      unbound cases of similar size. Larger targets present a more intensive sampling
      problem, and some large targets present repulsive barriers to entering the
      binding site. Ongoing improvements to RosettaDock's low-resolution search may
      alleviate this problem. This first public test suggests that RosettaDock can be
      useful in a significant range of applications in biochemistry and cell biology.

PMID- 15981263
TI  - ZDOCK and RDOCK performance in CAPRI rounds 3, 4, and 5.
AB  - We present an evaluation of the results of our ZDOCK and RDOCK algorithms in
      Rounds 3, 4, and 5 of the protein docking challenge CAPRI. ZDOCK is a Fast
      Fourier Transform (FFT)-based, initial-stage rigid-body docking algorithm, and
      RDOCK is an energy minimization algorithm for refining and reranking ZDOCK
      results. Of the 9 targets for which we submitted predictions, we attained at
      least acceptable accuracy for 7, at least medium accuracy for 6, and high
      accuracy for 3. These results are evidence that ZDOCK in combination with RDOCK
      is capable of making accurate predictions on a diverse set of protein complexes.

PMID- 15981264
TI  - Protein-Protein Docking Benchmark 2.0: an update.
AB  - We present a new version of the Protein-Protein Docking Benchmark, reconstructed
      from the bottom up to include more complexes, particularly focusing on more
      unbound-unbound test cases. SCOP (Structural Classification of Proteins) was used
      to assess redundancy between the complexes in this version. The new benchmark
      consists of 72 unbound-unbound cases, with 52 rigid-body cases, 13 medium
      difficulty cases, and 7 high-difficulty cases with substantial conformational
      change. In addition, we retained 12 antibody-antigen test cases with the antibody
      structure in the bound form. The new benchmark provides a platform for evaluating
      the progress of docking methods on a wide variety of targets. The new version of
      the benchmark is available to the public at http://zlab.bu.edu/benchmark2.

PMID- 15981265
TI  - Performance of the first protein docking server ClusPro in CAPRI rounds 3-5.
AB  - To evaluate the current status of the protein-protein docking field, the CAPRI
      experiment came to life. Researchers are given the receptor and ligand 3
      dimensional (3D) coordinates before the cocrystallized complex is published.
      Human predictions of the complex structure are supposed to be submitted within 3
      weeks, whereas the server ClusPro has only 24 h and does not make use of any
      biochemical information. From the 10 targets analyzed in the second evaluation
      meeting of CAPRI, ClusPro was able to predict meaningful models for 5 targets
      using only empirical free energy estimates. For two of the targets, the server
      predictions were assessed to be among the best in the field. Namely, for Targets
      8 and 12, ClusPro predicted the model with the most accurate binding-site
      interface and the model with the highest percentage of nativelike contacts, among
      180 and 230 submissions, respectively. After CAPRI, the server has been further
      developed to predict oligomeric assemblies, and new tools now allow the user to
      restrict the search for the complex to specific regions on the protein surface,
      significantly enhancing the predictive capabilities of the server. The
      performance of ClusPro in CAPRI Rounds 3-5 suggests that clustering the low free
      energy (i.e., desolvation and electrostatic energy) conformations of a
      homogeneous conformational sampling of the binding interface is a fast and
      reliable procedure to detect protein-protein interactions and eliminate false
      positives. Not including targets that had a significant structural rearrangement
      upon binding, the success rate of ClusPro was found to be around 71%.

PMID- 15981266
TI  - Improving CAPRI predictions: optimized desolvation for rigid-body docking.
AB  - The ICM Docking and Interface Side-Chain Optimization (ICM-DISCO) showed
      promising predictive results during the first CAPRI experiment by successfully
      finding medium- or high-accuracy models in 3 of the 7 targets. A key factor was
      the ability to recognize near-native rigid-body geometries in a relatively low
      number of alternative docking poses, together with the successful refinement of
      the rigid-body docking interfaces. Since then, we have focused on improving the
      scoring function to optimally discriminate the near-native rigid-body
      conformations. For that, we have defined a new desolvation descriptor for rigid
      body docking, based on atomic solvation parameters (ASPs) derived from octanol
      water transfer experiments. This and other new approaches have been gradually
      incorporated into our docking procedure during our participation on the second
      CAPRI experiment. Overall, we produced reasonable models for 8 of the 9 official
      targets. Especially encouraging were those cases in which a homology model of 1
      of the subunits had to be used during the docking simulations. And not less
      gratifying has been the successful prediction of antibody-antigen targets in a
      completely automatic, unrestrained fashion. In summary, our success rate (89%)
      shows a consistent improvement over the previous CAPRI rounds, and suggests that
      a correct desolvation description is key for improved protein-protein docking
      predictions.

PMID- 15981267
TI  - The targets of CAPRI rounds 3-5.
AB  - Ten protein-protein complexes have been offered by X-ray crystallographers as
      targets for structure prediction in Rounds 3-5 of the CAPRI experiment. They
      illustrate molecular recognition in several domains of biology: enzyme
      regulation, antigen-antibody recognition, signal transduction, and oligomer
      assembly. The targets presented various degrees of difficulty to the predictors,
      depending on their status (bound when components were taken from the complex,
      unbound when coming from independent structures of the free proteins), the
      amplitude of conformation changes, and the amount of biological information
      available. Predictors produced high-quality models of 6 of the targets, good
      models of 3 others, and failed only in 1 case, where the conformation change was
      particularly large. This result demonstrates significant progress relative to
      earlier rounds of CAPRI.

PMID- 15981268
TI  - Docking to single-domain and multiple-domain proteins: old and new challenges.
AB  - The diverse selection of targets in the CAPRI experiments provides grounds for
      determining the limits of our rigid-body docking program MolFit, and for
      extending it. We find that the sensitivity of MolFit is high, enabling it to
      produce reasonably accurate docking solutions when the structures undergo
      moderate local conformation changes upon complex formation or when the docked
      molecules are modeled. Yet the ranks of these solutions are sometimes too low to
      meet the requirements of CAPRI assessment. This indicates that the selectivity of
      MolFit, which was optimized for docking of unbound X-ray structures, and which
      relies on the availability of external data from biochemical and bioinformatic
      sources, needs readjustment in order to meet the challenges presented by NMR or
      modeled structures. A different challenge is presented by large global
      conformation changes such as movements of domains. We show that such changes can
      be accommodated within the rigid-body approximation by employing rigid multibody
      multistage docking procedures. We also address the difficulty of ranking results
      from 2-body and multibody docking scans in cases in which there are no external
      data favoring one option over the other.

PMID- 15981269
TI  - Geometry-based flexible and symmetric protein docking.
AB  - We present a set of geometric docking algorithms for rigid, flexible, and cyclic
      symmetry docking. The algorithms are highly efficient and have demonstrated very
      good performance in CAPRI Rounds 3-5. The flexible docking algorithm, FlexDock,
      is unique in its ability to handle any number of hinges in the flexible molecule,
      without degradation in run-time performance, as compared to rigid docking. The
      algorithm for reconstruction of cyclically symmetric complexes successfully
      assembles multimolecular complexes satisfying C(n) symmetry for any n in a matter
      of minutes on a desktop PC. Most of the algorithms presented here are available
      at the Tel Aviv University Structural Bioinformatics Web server
      (http://bioinfo3d.cs.tau.ac.il/).

PMID- 15981270
TI  - ATTRACT: protein-protein docking in CAPRI using a reduced protein model.
AB  - Protein-protein complex structures have been predicted for CAPRI Rounds 3 and 5
      using a reduced protein model. Proteins are represented by up to 3 pseudoatoms
      per amino acid. The docking approach termed ATTRACT is based on energy
      minimization in translational and rotational degrees of freedom of one protein
      with respect to another protein. The reduced protein model allows one to perform
      systematic docking minimization of many thousand start structures in reasonable
      computer time. Flexibility of critical surface side-chains can be accounted for
      by a multiple conformational copy approach. The multicopy approach allows
      simultaneous adjustment of side-chain conformations and optimization of
      translational and rotational degrees of freedom of one protein with respect to
      the partner during docking. For 3 (Targets 8, 14, and 19) out of 5 CAPRI targets,
      the approach resulted in predictions in close agreement with experiment [root
      mean-square deviation (RMSD) of backbone atoms within 10 A of the protein-protein
      interface < 1.8 A]. The comparison of predicted and experimental structures of
      the CAPRI targets indicates that besides local conformational changes (e.g.,
      changes in side-chain conformations), global conformational changes of the
      protein backbone can be critical for complex formation. These conformational
      changes not accounted for during docking are a likely reason for the unrealistic
      predictions in 2 cases (Targets 9 and 18).

PMID- 15981271
TI  - Protein-protein docking using 3D-Dock in rounds 3, 4, and 5 of CAPRI.
AB  - In rounds 3-5 of CAPRI, the community-wide experiment on the comparative
      evaluation of protein-protein docking for structure prediction, we applied the 3D
      Dock software package to predict the atomic structures of nine biophysical
      interactions. This approach starts with an initial grid-based shape
      complementarity search. The product of this is a large number of potential
      interacting conformations that are subsequently ranked by interface residue
      propensities and interaction energies. Refinement through detailed energetics and
      optimization of side-chain positions using a rotamer library is also performed.
      For rounds 3, 4, and 5 of the CAPRI evaluation, where possible, we clustered
      functional residues on the surfaces of the monomers as an indication of binding
      sites, using sequence based evolutionary conservations. In certain targets this
      provided a very useful tool for identifying the areas of interaction. During
      round 5, we also applied the techniques of side-chain trimming and geometrical
      clustering described in the literature. Of the nine target complexes in rounds 3
      5, we predicted conformations that contained at least some correct contact
      residues for seven of these systems. For two of the targets, we submitted
      predictions that were considered as medium-quality. These were a nidogen-laminin
      complex for target 8 (T08) and a serine-threonine phosphatase bound to a
      targeting subunit (T14). For a further three target systems, we produced models
      that were rated as acceptable predictions.

PMID- 15981272
TI  - Docking essential dynamics eigenstructures.
AB  - This article describes our attempts to dock the targets in CAPRI Rounds 3-5 using
      Hex 4.2, and it introduces a novel essential dynamics approach to generate
      multiple feasible conformations for docking. In the blind trial, the basic Hex
      algorithm found 1 high-accuracy solution for CAPRI Target 12, and several further
      medium- and low-accuracy solutions for Targets 11, 12, 13, and 14. Subsequent a
      posteriori docking of the targets using essential dynamics "eigenstructures" was
      found to give consistently better predictions than rigidly docking only the
      unbound or model-built starting structures. Some suggestions to improve this
      promising new approach are presented.

PMID- 15981273
TI  - Scoring docking models with evolutionary information.
AB  - We have developed methods for the extraction of evolutionary information from
      multiple sequence alignments for use in the study of the evolution of protein
      interaction networks and in the prediction of protein interaction. For Rounds 3,
      4, and 5 of the CAPRI experiment, we used scores derived from the analysis of
      multiple sequence alignments to submit predictions for 7 of the 12 targets. Our
      docking models were generated with Hex and GRAMM, but all our predictions were
      selected using methods based on multiple sequence alignments and on the available
      experimental evidence. With this approach, we were able to predict acceptable
      level models for 4 of the targets, and for a fifth target, we located the
      residues involved in the binding surface. Here we detail our successes and
      highlight several of the limitations and problems that we faced while dealing
      with particular docking cases.

PMID- 15981274
TI  - Generating controlled molecular gradients in 3D gels.
AB  - A new method for producing molecular gradients of arbitrary shape in thin three
      dimensional gels is described. Patterns are produced on the surface of the gel by
      printing with a micropump that dispenses small droplets of solution at controlled
      rates. The molecules in the solution rapidly diffuse into the gel and create a
      smooth concentration profile that is independent of depth. The pattern is
      relatively stable for long times, and its evolution can be accurately described
      by finite element modeling of the diffusion equation. As a demonstration of the
      method, direct measurements of protein gradients are performed by quantitative
      fluorescence microscopy. A complementary technique for measuring diffusion
      coefficients is also presented. This rapid, flexible, contactless approach to
      gradient generation is ideally suited for cell culture experiments to investigate
      the role of gradients of diffusible substances in processes such as chemotaxis,
      morphogenesis, and pattern formation, as well as for high-throughput screening of
      system responses to a wide range of chemical concentrations.

PMID- 15981275
TI  - Hydrodynamic study of biogranules obtained from an anaerobic hybrid reactor.
AB  - The bed expansion characteristics of a fluidized bed containing bacterial
      granules have been studied. These biogranules were obtained from an anaerobic
      hybrid reactor, which uses biogranules (without carrier particle) in fluidized
      condition. The settling velocity study of biogranules has shown that the drag
      coefficient of biogranule is greater than that of the rigid particle at the same
      Reynolds number. A new correlation based on this finding has been developed. The
      bed expansion study has demonstrated that a linear relationship exists between
      the natural logarithm of bed porosity and the natural logarithm of upflow
      superficial liquid velocity for the bed containing either a particular fraction
      of biogranule size or biogranules with wide size distribution. For a fluidized
      bed having a particular granule size, the bed porosity, and liquid superficial
      velocity could be related by the classic equation suggested by Richardson and
      Zaki (1954). The characteristic parameter of this correlation, the slope of the
      line n, has been related with Reynolds number. The intercept of the line gave a
      smaller value than the unhindered settling velocity of the particle. For
      fluidized bed having wide size distribution, the characteristic parameter n could
      not be related to Reynolds number. But the correlation suggested for single
      biogranule size has been found to predict n value with an average error of 2.3%.

PMID- 15981276
TI  - Simulation of gentamicin delivery for the local treatment of osteomyelitis.
AB  - In order to understand the effect of antibiotics delivery to bone tissue, by
      biodegradable polymeric drug disc, for the treatment of osteomyelitis, a three
      dimensional simulation model is developed. The simulation investigates the effect
      of pressure-induced convection on drug distribution, by taking into account the
      pressure gradient that exists between capillaries and interstitial space, and
      also as a result of the surgical opening. The clotting process at the surgical
      opening is incorporated into the simulation, and the effect of clotting duration
      is investigated. The clotting duration for the baseline simulation is 2 days and
      it is observed that increasing this duration depresses the mean drug
      concentration in the marrow and cortical bone. The effect of double burst release
      profile is also studied and it is observed that drug concentration drops too
      rapidly after the first burst to provide any therapeutic effect. However, it is
      shown that the drug concentration after the second burst stays above the minimum
      inhibitory concentration of the bacteria for a longer period of time, than would
      have been observed for a mono-burst release. Inserting non-biodegradable
      polymethylmethacrylate (PMMA) beads into bone seems to cause a higher average
      concentration of drug in the marrow. However, this could be brought about by the
      difference in the geometry between the disc and the bead, and the amount of drug
      packed in each bead. Further simulations on the management of dead space shows
      the ineffectiveness of having the void filled up with surgical gel as it becomes
      an additional barrier to drug delivery to the infected tissues.

PMID- 15981277
TI  - Optimization of tetracycline-responsive recombinant protein production and effect
      on cell growth and ER stress in mammalian cells.
AB  - The inducible T-REx system and other inducible expression systems have been
      developed in order to control the expression levels of recombinant protein in
      mammalian cells. In order to study the effects of heterologous protein expression
      on mammalian host behavior, the gene for recombinant Human transferrin (hTf) was
      integrated into HEK-293 cells and expressed under the control of the T-REx
      inducible technology (293-TetR-Hyg-hTf) or using a constitutive promoter (293-CMV
      hTf). A number of inducible clones with variable expression levels were
      identified for the T-REx system with levels of hTf for the high expressing clones
      nearly double those obtained using the constitutive cytomegalovirus (CMV)
      promoter. The level of transferrin produced was found to increase proportionately
      with tetracycline concentration between 0 and 1 mug/mL with no significant
      increases in transferrin production above 1 mug/mL. As a result, the optimal
      induction time and tetracycline concentrations were determined to be the day of
      plating and 1 mug/mL, respectively. Interestingly, the cells induced to express
      transferrin, 293-TetR-Hyg-hTf, exhibited lower viable cell densities and percent
      viabilities than the uninduced cultures for multiple clonal isolates. In
      addition, the induction of transferrin expression was found to cause an increase
      in the expression of the ER-stress gene, BiP, that was not observed in the
      uninduced cells. However, both uninduced and induced cell lines containing the
      hTf gene exhibited longer survival in culture than the control cells, possibly as
      a result of the positive effects of hTf on cell survival. Taken together, these
      results suggest that the high level expression of complex proteins in mammalian
      cells can limit the viable cell densities of cells in culture as a result of
      cellular stresses caused by generating proteins that may be difficult to fold or
      are otherwise toxic to cells. The application of inducible systems such as the T
      REx technology will allow us to optimize protein production while limiting the
      negative effects that result from these cellular stresses.

PMID- 15981278
TI  - Baculoviral polyhedrin-Bacillus thuringiensis toxin fusion protein: a protein
      based bio-insecticide expressed in Escherichia coli.
AB  - Previously, we found that baculoviral polyhedrin (Polh) used as a fusion partner
      for recombinant expression in Escherichia coli showed almost the same
      characteristics (rapid solubilization under alkaline conditions and specific
      degradation by specific alkaline proteases in insect midgut) as the native
      baculoviral Polh, and formed easily isolatable inclusion bodies. Here, Polh
      derived from the Autographa californica nuclear polyhedrosis virus (AcNPV) was
      fused with a Bacillus thuringiensis (Bt) toxin protein (truncated Cry1Ac having
      toxin region as a model Bt toxin) for the novel generation of a new bio
      insecticide. The Polh-Cry1Ac fusion protein (approximately 99 kDa) was highly
      expressed (3.6-fold induction as compared to E. coli-derived single Cry1Ac
      (approximately 68 kDa)) as an insoluble inclusion body fraction in E. coli.
      Trypsin and alpha-chymotrypsin, which have similar properties to the insect
      midgut alkaline proteases, rapidly degraded the Polh portion in vitro, leaving
      only the toxic Cry1Ac protein behind. In vivo, the Polh-Cry1Ac fusion protein
      showed high insecticidal activity against the pest, Plutella xylostella. Because
      this novel bio-insecticide employs E. coli as the host, mass production at a low
      cost should be possible. Also, since this is a protein-based insecticide, living
      modified organism (LMO) issues such as environmental and ecological safety can be
      avoided.

PMID- 15981279
TI  - Arsenite oxidation in batch reactors with alginate-immobilized ULPAs1 strain.
AB  - Arsenic is one of the major groundwater contaminants worldwide. It was previously
      demonstrated that the beta-proteobacterium Cenibacterium arsenoxidans has an
      efficient As[III] oxidation ability. The present study was conducted to evaluate
      the performance of alginate-immobilized ULPAs1 in the oxidation of As[III] to
      As[V] in batch reactors. A two-level full factorial experimental design was
      applied to investigate the influence of main parameters involved in the oxidation
      process, i.e., pH (7-8), temperature (4 degrees C-25 degrees C), kind of nutrient
      media (2%-20% sauerkraut brine), and arsenic concentration (10-100 mg/L). One
      hundred milligram per liter of As[III] was fully oxidized by calcium-alginate
      immobilized cells in 1 h. It was found that the temperature as well as the kind
      of nutrient media used were significant parameters at a 95% confidence interval
      whereas only temperature was a significant parameter at a 99% confidence
      interval. The immobilization of the As[III] oxidizing strain in alginate beads
      offers a promising way to implement new treatment processes in the remediation of
      arsenic contaminated waters.

PMID- 15981280
TI  - Epidermal growth factor receptor expression correlates with poor survival in
      patients who have breast carcinoma treated with doxorubicin-based neoadjuvant
      chemotherapy.
AB  - BACKGROUND: To the authors' knowledge there are few data that correlate the
      expression of the epidermal growth factor receptor (EGFR) with the outcome of
      patients who have breast carcinoma and are treated with anthracycline
      chemotherapy. METHODS: Pretreatment tumor tissue samples were available from 82
      patients who had locally advanced breast carcinoma and were treated on 2
      protocols investigating neoadjuvant 5-fluorouracil, doxorubicin, and
      cyclophosphamide chemotherapy. Immunohistochemical staining for EGFR (diluted
      1:50) was performed, and the staining results were interpreted without knowledge
      of outcome. RESULTS: Fourteen tumors (17%) were EGFR-positive, and 68 tumors
      (83%) were EGFR-negative. EGFR expression did not correlate with clinical stage
      (P = 0.361), HER-2/neu overexpression (P = 0.503), estrogen or progesterone
      receptor status (P = 0.631 and P = 0.838, respectively), nuclear grade (P =
      0.448), or proliferative index (P = 0.769). Patients who had EGFR-positive tumors
      had a worse 5-year disease-free survival (DFS) rate (46% vs. 76%; P = 0.026) and
      overall survival (OS) rate (46% vs. 76%; P = 0.037) compared with patients who
      had EGFR-negative tumors. The pathologic complete response rate did not differ
      between the 2 groups (P = 0.389), although patients with EGFR-positive disease
      more commonly had > or = 4 positive lymph nodes after chemotherapy (64% vs. 29%;
      P = 0.028). EGFR expression continued to show a significant correlation with
      poorer DFS and OS in a Cox regression analysis model that included the presence
      or absence of four or more lymph nodes and EGFR status. CONCLUSIONS: EGFR
      expression may have prognostic significance in patients with locally advanced
      breast carcinoma who are treated with anthracycline chemotherapy. These data
      warrant further studies aimed at correlating EGFR expression and outcome in
      patients who have breast carcinoma treated with doxorubicin-based chemotherapy.

PMID- 15981281
TI  - The prognostic relevance of molecular alterations in glioblastomas for patients
      age < 50 years.
AB  - BACKGROUND: In patients with glioblastoma, age < 50 years was identified as a
      consistent prognostic variable. In addition, the prognosis for these patients may
      be determined by a complex interaction between age and genetic alterations. The
      objective of the current study was the molecular analysis of glioblastomas from
      adult patients age < 50 years ("young adults"). METHODS: The authors analyzed a
      set of 189 glioblastoma specimens. Fluorescence in situ hybridization was
      performed with a set of 10 chromosome probes (1p36, 1q25, centomere probe 7
      [CEP7], 7p12/epidermal growth factor receptor gene (EGFR), CEP9, 9p21/p16, CEP10,
      10q23/phosphatase and tesnin homolog gene (PTEN), 19p13, and 19q13). RESULTS:
      Patient age < 40 years was associated strongly with a favorable prognosis.
      Patients age > or = 40 years frequently showed EGFR amplification, loss of 9p,
      loss of 10q, and gain of chromosome 19. The patients with - 19q were age < 40
      years. The survival was shorter for patients with EGFR amplification, gain of
      chromosome 7, loss of 9p, loss of 10q, and gain of chromosome 19. In contrast,
      the patients who had tumors with gain of chromosome 9 or loss of 19q had more
      favorable outcomes. In a multivariate analysis, gain of chromosome 9 (P = 0.026)
      and loss of 10q23 (P = 0.007) reached the level of independent prognostic value.
      In addition, the prognostic value of molecular alterations in patients age < 40
      years and patients age > 40 years were examined separately. Consequently, EGFR
      amplification, - 9p, and + 9 were significant for both age groups, whereas gain
      of chromosome 7 and loss of 10q showed clinical importance only among patients
      age > 40 years. CONCLUSIONS: Adult patients age < 50 years with glioblastoma had
      molecularly distinct disease, and the age-dependent heterogeneity seen on the
      chromosomal level also applied at the clinical level.

PMID- 15981282
TI  - Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale
      single-institution review.
AB  - BACKGROUND: Sarcomas are a rare complication of radiotherapy for breast carcinoma
      and patients have a poor prognosis. The incidence, histology, and management of
      patients with sarcomas were reviewed in the current study. METHODS: The authors
      reviewed the records of 16,705 patients with breast carcinoma. Of these, 13,472
      (81%) were treated with megavoltage radiotherapy and 3233 were treated without at
      the Institute Curie (Paris, France) between 1981 and 1997. Median doses of 50-55
      grays (Gy) in 25-27 fractions were delivered to the whole breast over a period of
      5-5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when indicated, by a 16-26
      Gy boost to the tumor or tumor bed. Treatment of radiation-induced sarcomas (RIS)
      consisted mostly of radical surgery and chemotherapy. RESULTS: Overall, 35
      patients developed sarcomas. Of these, 27 fulfilled the Cahan criteria. The
      median follow-up was 9.3 years (range, 1-22.4 years). The latency period ranged
      from 3 years to 20.3 years. Thirteen sarcomas were located in the breast, 5- in
      the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula, and 3
      in the axilla. Histologic evaluation identified 13 angiosarcomas, 3
      osteosarcomas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2
      leiomyosarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The
      cumulative RIS incidence was 0.07% (+/- 0.02) at 5 years, 0.27% (+/- 0.05) at 10
      years, and 0.48% (+/- 0.11) at 15 years. Standardized incidence ratios were 10.2
      (95% confidence interval, 9.03-11.59) for irradiated patients and 1.3 (0.3-3.6)
      for nonirradiated patients. Of the 27 patients, 15 died of sarcoma within 1 month
      to 14.5 years (mean, 34.2 +/- 0.7 months). The 5-year actuarial survival rate
      after diagnosis of RIS was 36% (+/- 0.11). CONCLUSIONS: The current study
      confirmed the rarity of RIS. However, it showed that the risk increased with
      time. Therefore, careful, long-term follow-up of patients treated with
      radiotherapy is needed for early detection and efficacious treatment of these
      malignancies.

PMID- 15981283
TI  - Incidence of anaphylactoid reactions to isosulfan blue dye during breast
      carcinoma lymphatic mapping in patients treated with preoperative prophylaxis:
      results of a surgical prospective clinical practice protocol.
AB  - BACKGROUND: Severe anaphylactoid reactions to isosulfan blue dye requiring
      resuscitation are reported to occur in 1.1% of patients with breast carcinoma
      undergoing sentinel lymphadenectomy. In December 2001, the authors began
      administering a prophylactic regimen before dye injection to determine whether
      prophylaxis reduced the incidence of life-threatening reactions. METHODS: All
      patients were mapped with technetium-99m-labeled sulfur colloid. Those also
      receiving isosulfan blue dye were administered a glucocorticoid, diphenhydramine,
      and famotidine intravenously just before or at induction of anesthesia. Adverse
      reactions at the time of surgery were analyzed. RESULTS: Between December 2001
      and July 2003, 1013 consecutive patients underwent sentinel lymphadenectomy for
      breast carcinoma. Six hundred sixty-seven patients (65.8%) received prophylaxis
      and isosulfan blue dye, 33 (3.3%) received prophylaxis but no dye, 12 (1.2%)
      received dye but no prophylaxis, and 301 (29.7%) received no prophylaxis or dye.
      Blue urticaria and facial edema were observed in 3 (0.5%) of 667 patients
      receiving prophylaxis and dye and in 1 (8.3%) of 12 patients receiving dye but no
      prophylaxis. There were no episodes of hypotension, and no patients required
      vasopressors, ventilatory support, or intensive care observation. Adverse
      reactions to agents other than blue dye were observed in 2 (0.3%) of 667 patients
      receiving prophylaxis and dye and in 3 (1.0%) of 301 receiving no prophylaxis and
      no dye (P = 0.1773). CONCLUSIONS: Preoperative prophylaxis was found to reduce
      the severity, but not the overall incidence, of adverse reactions to isosulfan
      blue dye. No life-threatening reactions were noted in patients treated with
      preoperative prophylaxis. Based on these results, the authors now routinely
      recommend administration of prophylaxis to patients receiving isosulfan blue for
      lymphatic mapping and sentinel lymph node biopsy.

PMID- 15981284
TI  - Proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus.
AB  - BACKGROUND: Treatment modalities for patients with hepatocellular carcinoma (HCC)
      who have portal vein tumor thrombus (PVTT) are limited and controversial;
      furthermore, the prognosis for these patients is extremely poor. The authors
      conducted a retrospective review to determine the role of proton beam therapy in
      the treatment of patients who had HCC with PVTT. METHODS: Twelve patients with
      HCC who had tumor thrombus in the main trunk or major branches of the portal vein
      (clinical T3-T4N0M0) were treated with proton beam therapy. At the time they
      received proton beam irradiation, patients ranged in age from 42 years to 80
      years (median, 62 years), and their tumors ranged in size from 40 mm to 110 mm
      (median, 60 mm) in greatest dimension. A total dose of 50-72 gray (Gy) (median,
      55 Gy) in 10-22 fractions was delivered to the tumors, including PVTT. RESULTS:
      All tumors that were treated with proton beam therapy remained controlled at a
      median follow-up of 2.3 years (range, 0.3-7.3 years). Among 12 patients, 10
      patients had new liver tumors outside the irradiated volume 0.1-2.4 years after
      proton beam therapy, and 3 patients also had distant metastases; consequently, 8
      patients died of disease, and 2 patients were salvaged by further therapies. The
      remaining two patients were alive with no evidence of disease 4.3 years and 6.4
      years after proton beam therapy. The progression-free survival rates were 67% at
      2 years and 24% at 5 years. The median progression-free survival was 2.3 years.
      According to the Acute Radiation Morbidity Scoring Criteria (Radiation Therapy
      Oncology Group), therapy-related toxicity > or = Grade 3 was not observed.
      CONCLUSIONS: Proton beam therapy for patients with HCC who had PVTT was feasible
      and effective. It appeared to improve survival and local control significantly
      for these patients.

PMID- 15981285
TI  - Residual dipolar couplings--a valuable NMR parameter for small organic molecules.

PMID- 15981286
TI  - Molecular-weight-tagged glycopeptide library: efficient construction and
      applications.

PMID- 15981287
TI  - Artificial glycosyl phosphorylases.
AB  - alpha- and beta-Cyclodextrin 6(A),6(D)-diacids (1 and 2), beta-cyclodextrin-6
      monoacid (14), beta-cyclodextrin 6(A),6(D)-di-O-sulfate (16) and beta
      cyclodextrin-6-heptasulfate (19) were synthesised. Acids 1, 2 and 14 were made
      from perbenzylated alpha- or beta-cyclodextrin, by diisobutylaluminum hydride
      (DIBAL)-promoted debenzylation, oxidation and deprotection. Addition of molecular
      sieves was found to improve the debenzylation reaction. Sulfates 16 and 19 were
      made by sulfation of the appropriately partially protected derivatives and
      deprotection. Catalysis of 4-nitrophenyl glycoside cleavage by these cyclodextrin
      derivatives was studied. Compounds 1, 2 and 16 were found to catalyse the
      reaction, with the catalysis following Michaelis-Menten kinetics and depending
      first order on the phosphate concentration. In a phosphate buffer (0.5 M, 59
      degrees C, pH 8.0), K(M) varied from 2-10 mM and the k(cat)/k(uncat) ratio from
      80-1000 depending on the stereochemistry of the substrate and the catalyst, with
      2 being the best catalyst and with the sulfated 16 also displaying catalytic
      ability. The monoacid 14 and the heptasulfate 19 were not catalytic.

PMID- 15981288
TI  - Photocatalytic nanodiodes for visible-light photocatalysis.

PMID- 15981289
TI  - Mining the tetraene manifold: total synthesis of complex pyrones from
      Placobranchus ocellatus.

PMID- 15981290
TI  - An anomalous endohedral structure of Eu@c82 metallofullerenes.

PMID- 15981292
TI  - Synthesis of an optically active C1-symmetric Al(salalen) complex and its
      application to the catalytic hydrophosphonylation of aldehydes.

PMID- 15981291
TI  - [2+1] cycloadditions of terminal alkynes to norbornene derivatives catalyzed by
      palladium complexes with phosphinous acid ligands.

PMID- 15981293
TI  - Tweezering the core of a dendrimer: a photophysical and electrochemical study.

PMID- 15981294
TI  - Enantioselective hydrogenation of allylphthalimides: an efficient method for the
      synthesis of beta-methyl chiral amines.

PMID- 15981295
TI  - Individual growth curve models for assessing evidence-based referral criteria in
      growth monitoring.
AB  - The goal of this study is to assess whether a growth curve model approach will
      lead to a more precise detection of Turner sydnrome (TS) than conventional
      referral criteria for growth monitoring. The Jenss-Bayley growth curve model was
      used to describe the process of growth over time. A new screening rule is defined
      on the parameters of this growth curve model, parental height and gestational
      age. The rule is applied to longitudinal growth data of a group of children with
      TS (n=777) and a reference (n=487) group. The outcome measures are sensitivity,
      specificity and median referral age. Growth curve parameters for TS children were
      different from reference children and can therefore be used for screening. The
      Jenss-Bayley growth model, which uses all longitudinal measurements from birth to
      a maximum age of 5 years with at least one measurement after the age of 2,
      together with parental height and gestational age can achieve a sensitivity of
      85.2 per cent with a specificity of 99.5 per cent and a median referral age of
      4.2 (the last measurement between the age of 2 and 5 of each child is considered
      to be the moment of referral). Sensitivity increases by 2 percentage points when
      decreasing the specificity to 99 per cent. The Jenss-Bayley growth model from
      birth to a maximum age of 8 years with at least one measurement after the age of
      2, together with parental height results in a sensitivity of 89.0 per cent with a
      specificity of 99.5 per cent and a median referral age of 6.1. For a specificity
      of 98 per cent, we obtain a sensitivity of 92.3 per cent. In comparison to
      conventional rules applied to the same data, sensitivity is about 11-30
      percentage points higher at the same level of specificity for the Jenss-Bayley
      growth rule. We conclude that from the age of 4, growth curve models can improve
      the screening on TS to conventional screening rules.

PMID- 15981296
TI  - A rejuvenation method for poly(N,N-dimethylacrylamide)-coated glass microfluidic
      chips.
AB  - As microfluidic chips come to integrate the higher levels of functionality
      required for the implementation of advanced bioanalytical protocols, a crucial
      factor is that of cost. Although glass chips provide advantages in multilayer
      integrations, their cost is far higher than that of polymer chips. However, a
      simple and effective rejuvenation protocol for glass microchips may enable higher
      levels of integration and functionality on glass microchips. Here we present a
      method to rejuvenate glass microchips that had been used for capillary
      electrophoresis to the extent that their performance was degraded. This
      degradation was due to one of the two mechanisms: (i) a deterioration of the
      polymer coating on the inner surface of the microchannel or (ii) an aging of the
      glass substrate. Using the method presented here, we have rejuvenated more than
      50 such "aged" microchips. The performance of these microchips was fully restored
      after the rejuvenation and lasted for hundreds of DNA separation runs. Our
      experiments indicate that the loss of resolution in microchip separations was not
      associated with glass aging, but was due to the degradation of the polymer
      coating on the inner surface of microchannels. This suggests that it is possible
      to extend the microchip lifetime "forever" using the rejuvenation protocol and
      that the exploration of higher levels of integration and functionality on glass
      microchips (or of hybrid structures involving materials capable of withstanding
      the reagents and elevated temperatures used) is feasible.

PMID- 15981297
TI  - Pilot study of capillary electrophoresis coupled to mass spectrometry as a tool
      to define potential prostate cancer biomarkers in urine.
AB  - We describe the use of capillary electrophoresis (CE) coupled with mass
      spectrometry (MS) to identify single polypeptides and patterns of polypeptides
      specific for prostate cancer (CaP) in human urine. Using improved sample
      preparation methods that enable enhanced comparability between different samples,
      we examined samples from 47 patients who underwent prostate biopsy. Of this
      group, 21 patients had benign pathology and 26 with CaP, and these were used to
      define potential biomarkers, which allow discrimination between these two states.
      In addition, CE-MS data from these 47 urine samples were compared to that of 41
      young men (control) without known or suspected clinical CaP to further confirm
      the polypeptides indicative for CaP. Upon crossvalidation of the same samples,
      several polypeptides were selected that enabled correct classification of the CaP
      patients with 92% sensitivity and 96% specificity. We then examined an additional
      474 samples from patients with renal disease enrolled in other studies and found
      that 14 (3%) had polypeptides suggestive of CaP possibly indicating that they
      harbor clinical CaP. In conclusion, this early pilot study suggests that CE-MS of
      urine warrants further investigation as a tool that can identify putative
      biomarkers for CaP.

PMID- 15981298
TI  - Proteomic analysis of slow- and fast-twitch skeletal muscles.
AB  - Skeletal muscles are composed of slow- and fast-twitch muscle fibers, which have
      high potential in aerobic and anaerobic ATP production, respectively. To
      investigate the molecular basis of the difference in their functions, we examined
      protein profiles of skeletal muscles using sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and two-dimensional gel electrophoresis with pH 4-7 and 6-11
      isoelectric focusing gels. A comparison between rat soleus and extensol digitorum
      longus (EDL) muscles that are predominantly slow- and fast-twitch fibers,
      respectively, showed that the EDL muscle had higher levels of glycogen
      phosphorylase, most glycolytic enzymes, glycerol 3-phosphate dehydrogenase, and
      creatine kinase; while the soleus muscle had higher levels of myoglobin, TCA
      cycle enzymes, electron transfer flavoprotein, and carbonic anhydrase III. The
      two muscles also expressed different isoforms of contractile proteins including
      myosin heavy and light chains. These protein patterns were further compared with
      those of red and white gastrochnemius as well as red and white quadriceps
      muscles. It was found that metabolic enzymes showed a concerted regulation
      dependent on muscle fiber types. On the other hand, expression of contractile
      proteins seemed to be independent of the metabolic characteristics of muscle
      fibers. These results suggest that metabolic enzymes and contractile proteins
      show different expression patterns in skeletal muscles.

PMID- 15981299
TI  - A novel synthesis and molluscicidal activity of some functionally substituted
      pyridine, pyrido[3,2-c]pyridazine, and pyrido[3,2-c]pyridazino[2',3'
      a]quinazoline derivatives.
AB  - Ethyl benzoylacetate reacts with the malononitrile dimer to afford 4-amino-5
      benzoyl-2-dicyano methyl-6-hydroxypyridine, which undergoes the coupling reaction
      with aromatic diazonium salts to afford azo derivatives. These azo derivatives
      could be cyclized into pyrido[3,2-c]pyridazine and pyrido[3,2-c]pyridazino[2',3'
      a]quinazoline derivatives upon reflux in ethanolic NaOH, presumably via their
      hydrazo tautomers. The molluscicidal activity of these compounds was evaluated.

PMID- 15981300
TI  - Stress and active oxygen species--effect of alpha-tocopherol on stress response.
AB  - Stress is implicated in the pathogenesis of numerous disorders such as
      cardiovascular diseases or neurodegeneration. The extensive overlap between
      diseases attributed to stress and oxidative damage is indicative of their
      potential relationship. We hereby study the influence of alpha-tocopherol (alpha
      toc) on the development of stress biomarkers (morphological and biochemical), on
      specific biomarkers of radical insult (lipid peroxidation, oxidized proteins, or
      glutathione content in brain and liver), as well as on drug metabolism. In our
      experimental protocol two groups of female rats are exposed to stress conditions,
      i.e. cold plus starvation. Before stress and during its application one group is
      treated with alpha-toc for 20 d (0.42 mmol/kg per os, once daily). Our results
      indicate that oxidative damage accompanies the development of stress, while
      treatment with alpha-toc completely prevents stress-induced radical attack and
      reduces stress indices like plasma corticosterone, uropepsinogen, and
      morphological changes. It is found that stress increases the drug metabolic
      potential of the liver (total P450, CYP2E1, or CYP3A1 activity). Administration
      of alpha-toc, in combination with stress, further increases erythro mycin N
      demethylation (CYP3A1) compared to stress control, while 4-nitrophenol
      hydroxylation (CYP2E1) is not affected significantly.

PMID- 15981301
TI  - Evaluation of antimicrobial activities of several mannich bases and their
      derivatives.
AB  - The aim of this study was to evaluate the antimicrobial activities of several
      Mannich bases and their derivatives against pathogenic bacteria and fungi. 3
      Dimethylamino-1-phenyl-1-propanone hydrochloride (Ig1) as mono-Mannich base,
      bis(beta-aroylethyl)methylamine hydrochlorides (B1, B5) as bis-Mannich bases, 3
      aroyl-4-aryl-1-methyl-4-piperidinol hydrochlorides (C1, C5) as piperidinol
      derivatives, which are structural isomers of bis-Mannich bases, N,N'-Bis(3
      dimethylamino-1-phenylpropylidene)hydra zine dihydrochlorides (D1) as azine
      derivative of mono-Mannich base Ig1, and some representative quaternary
      derivatives (Ig4 and C6), which are quaternary derivatives of Ig1 and C1,
      respectively, have been synthesized. Aryl parts were phenyl in B1 and C1, and 2
      thienyl in B5 and C5. Bis-Mannich bases and quaternary Mannich bases were found
      to be effective antifungal derivatives. Quaternary mono-Mannich base Ig4 has
      shown twice the amount of higher antifungal potency against the human pathogenic
      fungus Microsporum canis compared with the reference drug amphotericin-B and it
      had equal potency against many other fungi species pathogenic in humans and
      plants. Ig4 was effective against Staphylococcus aureus among the bacteria
      tested. Preparation of bis-Mannich bases and qua ternization procedure seemed
      suitable chemical modifications to prepare effective antifungal compounds.
      Especially quaternary derivatives Ig4, and to some extent C6, seem to be model
      compounds to develop new antimicrobial agents for further studies.

PMID- 15981303
TI  - Methods in pharmacoepidemiology: an invited series.

PMID- 15981304
TI  - Cephalosporin utilization in the inpatient wards of a teaching hospital in
      Western Nepal.

PMID- 15981305
TI  - The reverse propensity score to detect selection bias and correct for baseline
      imbalances.
AB  - The propensity score has been proposed, and for the most part accepted, as a tool
      to allow for the evaluation of medical interventions in the presence of baseline
      imbalances arising in the context of observational studies. The lack of an
      analogous tool to allow for the evaluation of medical interventions in the
      presence of potentially systematic baseline imbalances in randomized trials has
      required the use of ad hoc methods. This, in turn, leads to challenges to the
      conclusions. For example, much of the controversy surrounding recommendations for
      or against mammography for some age groups stems from the fact that all the
      randomized trials to study mammography had baseline imbalances, to some extent,
      in important prognostic covariates. While some of these trials used cluster
      randomization, baseline imbalances are prevalent also in individually randomized
      trials. We provide a systematic approach for evaluating medical interventions in
      the presence of potentially systematic baseline imbalances in individually
      randomized trials with allocation concealment. Specifically, we define the
      reverse propensity score as the probability, conditional on all previous
      allocations and the allocation procedure (restrictions on the randomization),
      that a given patient will receive a given treatment. We demonstrate how the
      reverse propensity score allows for both detection of and correction for
      selection bias, or systematic baseline imbalances.

PMID- 15981307
TI  - Antidepressants and the placebo response.

PMID- 15981308
TI  - Effects of socio-demographic variables on health-related quality of life
      determined by the quality of life index--German version.
AB  - STUDY OBJECTIVE: The purpose of this study was to determine subjective health
      related quality of life (HRQoL) in a sample of the Austrian population over 14
      years of age in order to evaluate the effect of socio-demographic variables on
      HRQoL. DESIGN/SETTING: HRQoL was determined by means of the quality of life index
      German version (QLI-Ge). The influence of socio-demographic variables on HRQoL
      was assessed by statistical analysis using the Kruskal-Wallis test and an
      analysis of variance. PARTICIPANTS: A random-quota procedure was used to get
      balanced representation from regions and demographic groups of the Austrian
      population. The sample consisted of 1049 participants, 493 men and 556 women.
      MAIN RESULTS: Age was found to influence the QLI-Ge total score (index score) and
      most individual items, with increasing age resulting in a decrease in HRQoL.
      Differences between the sexes were observed in three dimensions: males scored
      higher in 'physical well-being', 'psychological well-being' and 'occupational
      functioning'. Marital status impacted most items with married persons showing
      better values than divorced persons or singles. Profession had only a minor
      effect on HRQoL, the level of education showed no influence at all. CONCLUSIONS:
      The socio-demographic variables age, sex and objective living conditions had a
      major influence on subjectively rated HRQoL, whereas profession and education
      were found to play a minor role in this context. It is recommended that in the
      interpretation of studies assessing HRQoL the above-mentioned objective factors
      be considered. This will be of particular importance when determining the effect
      of a pharmacotherapy on HRQoL in patients.

PMID- 15981310
TI  - The 10 billion dollar battle. Governors also refuse to join Medicaid Commission.

PMID- 15981311
TI  - Fast parallel molecular solutions for DNA-based supercomputing: the subset
      product problem.
AB  - In this paper our main purpose is to give molecular solutions for the subset
      product problem. In order to achieve this, we propose three DNA-based algorithms-
      parallel adder, parallel multiplier and parallel comparator--that formally verify
      our designed molecular solutions for the subset-product problem. We also show
      that Boolean circuits are not needed to perform mathematical operations on a
      molecular computer. Furthermore, this work indicates that the subset-product
      problem is solved and also presents clear evidence of the ability of molecular
      computing to perform complicated mathematical operations.

PMID- 15981312
TI  - Morphine, gabapentin, or their combination for neuropathic pain.

PMID- 15981313
TI  - External defibrillators.

PMID- 15981314
TI  - Blast injuries.

PMID- 15981315
TI  - Blast injuries.

PMID- 15981316
TI  - [Benign monoclonal dysglobulinemias in Shanghai].

PMID- 15981317
TI  - [Semi quantitative determination of blood procalcitonin by the
      immunochromatographic BRAHMS PCT-Q test: false positive result].

PMID- 15981318
TI  - Design and implementation of a mosquito database through an entomological
      ontology.
AB  - There have been constant changes in the biology and behavior of the vector and
      parasite involved in the transmission of malaria. There is limited interest in
      developing new technologies and procedures for controlling the underlying factors
      of this threat, which poses an enormous challenge to health systems. To
      understand the various vector species and their interrelations is of prime
      importance in understanding the transmission mechanisms of malaria in order to
      react efficiently. To attain this objective, we have used an ontological approach
      to produce a database that we consider to be our own contribution in helping to
      control malarial vectors if eradication has been unsuccessful in the previous
      control campaign.

PMID- 15981319
TI  - Aging and immune function. Summary of a workshop held at Trudeau Institute,
      Saranac Lake, NY.

PMID- 15981320
TI  - The radiation sensitivity of Escherichia coli B: a hypothesis relating filament
      formation and prophage induction. 1967.

PMID- 15981321
TI  - Fixing a broken record. Visualizing 'career space' can help you navigate more
      easily between disciplines, sectors and job function.

PMID- 15981322
TI  - Picture this. Buoyed by a range of new technologies.

PMID- 15981323
TI  - SOS replication: a distinct DNA replication mechanism which is induced by DNA
      damaging treatments? 1970.

PMID- 15981324
TI  - The first US-Japan meeting on error-prone DNA synthesis, Maui, Hawaii, December
      20-21, 2004.

PMID- 15981325
TI  - Problems in patenting human genes.

PMID- 15981326
TI  - Influence of transposable elements on the structure and function of the A1 gene
      of Zea mays.
AB  - The structure of the A1 gene of Zea mays was determined by sequencing cDNA and
      genomic clones. The gene is composed of four exons and three short introns. The
      40.1-kd A1 protein is an NADPH-dependent reductase. Germinal derivatives of the
      mutable a1-m1 allele with either recessive or wild-type phenotype have been
      isolated. Sequence analysis of these revertant alleles indicates that frame-shift
      mutations abolish A1 gene function, whereas one additional amino acid within the
      protein sequence still allows wild-type gene expression. The presence of a
      second, promoter-like structure, upstream of the functional A1 gene promoter is
      discussed with respect to its possible involvement in differential expression of
      the A1 gene. The structure of the a1-m2 8004, 3456 and 4412 alleles, featuring
      distinguishable phenotypes in the presence of Spm(En), was also determined. In
      all alleles the 1080-bp-long inhibitor (I) element is located 15 bp upstream of
      the CAAT box of the A1 gene promoter. The unusual response of a1-m2 alleles to
      trans-active signals of the Spm(En) element is discussed with respect to the
      position of the I inserts. Also presented are data on the structure and insertion
      sites of transposable elements determined by cloning and sequencing of the
      mutable a1 alleles a1-mpapu, a1-mr 102 and a1-ml.

PMID- 15981327
TI  - Wound expression of a potato proteinase inhibitor II gene in transgenic tobacco
      plants.
AB  - A potato proteinase inhibitor II gene was transferred into tobacco plants using
      Agrobacterium/Ti-plasmid-mediated gene transfer techniques. Whereas no or little
      expression of the proteinase inhibitor II gene could be detected in non-wounded
      leaves, high levels of proteinase inhibitor II mRNA were detected in leaves of
      several transgenic tobacco plants after mechanical wounding as well as after
      treatment of detached leaves with oligosaccharides. Wounding of a leaf also led
      to a systemic induction in non-wounded leaves as well as non-wounded stem, and
      roots. RNA-protection experiments showed that the transcription of the proteinase
      inhibitor gene in transgenic tobacco plants was initiated at the same nucleotide
      as that of the original gene. These observations demonstrate that although no
      proteinase inhibitor II homologous gene can be detected in tobacco, this plant
      nevertheless has the capacity to regulate the expression of the potato gene in
      the same complex manner as in the case of potato.

PMID- 15981328
TI  - Expression of bacterial chloramphenicol acetyltransferase gene in tobacco plants
      mediated by TMV-RNA.
AB  - We have constructed three tobacco mosaic virus (TMV) cDNA derivatives by
      modification of the full-length cDNA clone from which infectious TMV-RNA can be
      transcribed in vitro. A coatless TMV construct lacks most of the coat protein
      gene and chimeric TMV constructs retain the bacterial chloramphenicol
      acetyltransferase (CAT) gene in place of the coat protein gene. When in vitro
      transcripts from these cDNA derivatives were inoculated on the local lesion
      tobacco plants, TMV-specific lesions were produced. In the case of the TMV-CAT
      chimeras, however, the lesions were small compared to those of wild-type TMV and
      those produced by transcript derived from the coatless construct. Northern blot
      analysis of RNA extracted from the inoculated leaves of the systemic host plants
      revealed replication of the derivative genomic RNAs and production of their own
      subgenomic RNAs corresponding to the coat protein mRNA. The TMV-CAT chimeras
      produced biologically active CAT in the inoculated leaves of the systemic host.
      CAT activity increased at least until 2 weeks post-inoculation and was
      approximately 0.1 units/mg of tissue at 10 days post-inoculation. Thus, TMV-RNA
      may be utilized as a new plant expression vector.

PMID- 15981329
TI  - Maize Adh-1 promoter sequences control anaerobic regulation: addition of upstream
      promoter elements from constitutive genes is necessary for expression in tobacco.
AB  - The promoter region of a maize alcohol dehydrogenase gene (Adh-1) was linked to a
      reporter gene encoding chloramphenicol acetyl transferase (CAT) and transformed
      stably into tobacco cells using T-DNA vectors. No CAT enzyme activity could be
      detected in transgenic tobacco plants unless upstream promoter elements from the
      octopine synthase gene or the cauliflower mosaic virus 35S promoter were supplied
      in addition to the maize promoter region. CAT enzyme activity and transcription
      of the chimaeric gene were then readily detected after anaerobic induction. The
      first 247 bp upstream of the translation initiation codon of the maize Adh-1 gene
      were sufficient to impose anaerobic regulation on the hybrid gene and S1 nuclease
      mapping confirmed mRNA initiation is from the normal maize Adh-1 transcription
      start point.

PMID- 15981330
TI  - Binding of a nuclear factor to a consensus sequence in the 5' flanking region of
      zein genes from maize.
AB  - The genomic organization of the zein structural genes and of regulatory loci
      influencing their expression suggests that control of zein gene expression will
      involve interactions between cis elements in the flanking DNA sequences and
      products from trans-acting genes. The interaction between fragments from the 5'
      flanking region of a zein gene and specific, double-stranded oligonucleotides
      with crude nuclear extracts from maize endosperm have been studied by
      nitrocellulose filter binding, gel retention and DNase I footprinting assays.
      Specific binding of a nuclear factor was observed and the exact position of the
      protein binding site was determined. The 22-nt binding site included 14 bp of a
      15-bp sequence conserved in all zein genes.

PMID- 15981331
TI  - Identification of plant-induced genes of the bacterial pathogen Xanthomonas
      campestris pathovar campestris using a promoter-probe plasmid.
AB  - A promoter-probe plasmid suitable for use in Xanthomonas campestris pathovar
      campestris (causal agent of crucifer black rot) was constructed by ligating a
      broad host range IncQ replicon into the promoter-probe plasmid pKK232-8, which
      contains a promoterless chloramphenicol acetyltransferase gene. Xanthomonas
      chromosomal DNA fragments were 'shotgun' cloned into a restriction site in front
      of this gene, and the resulting library was transferred en masse into
      Xanthomonas. Individual transconjugants possessing DNA insertions with promoter
      activity in plants were identified by virtue of their ability to infect
      chloramphenicol-treated turnip seedlings. Of 19 transconjugants identified in
      this way five were chloramphenicol resistant both in turnip seedlings and on agar
      plates. However the remaining 14 were only chloramphenicol resistant in planta,
      and thus apparently contained plant-inducible promoter fragments. Resistance to
      chloramphenicol was correlated with increased chloramphenicol acetyltransferase
      activity for the transconjugants assayed. The promoter fragments were used to
      isolate genomic clones from a library, and the role of the genes contained in
      these clones in pathogenicity is being investigated.

PMID- 15981333
TI  - The determination of mother cell-specific mating type switching in yeast by a
      specific regulator of HO transcription.
AB  - In haploid homothallic budding yeast, cell division gives rise to a mother cell
      which proceeds to switch its mating type and a daughter cell (the bud) which does
      not. Switching is initiated by a specific double strand cleavage of mating type
      DNA by an endonuclease encoded by the HO gene. Previous data suggest that the
      pattern of HO transcription is responsible for the mother cell specificity of
      switching. HO is transcribed transiently, at START, during the cell cycle of
      mother cells but not at all during the cell cycle of daughter cells. The HO
      promoter is complex. Sequences between -1000 and -1400 (called URS1) are
      essential for transcription, whereas sequences between -150 and -900 (called
      URS2) are necessary for cell cycle control. Moreover, 10 trans-acting gene
      products called SWI1-10 are necessary for maximum expression. In an attempt to
      identify the cis-acting DNA sequences which are responsible for mother cell
      specificity and to identify which SW1 genes are involved, a hybrid GAL/HO
      promoter was constructed in which the upstream activation region putatively
      involved in mother cell-specific activation (URS1) is replaced by the upstream
      activation region of the GAL1-10 promoter. The properties of this hybrid promoter
      show, for the first time, that: (i) the HO promoter is modular since mother cell
      specificity can be replaced by galactose dependence without compromising cell
      cycle control or a/alpha repression; (ii) transcription of HO is indeed the major
      rate-limiting event for switching which is absent in daughter cells; (iii)
      SWI1,2,3, 4,6,7,8.9 and 10 are unlikely to be involved in mother cell specificity
      but SW15 probably is.

PMID- 15981332
TI  - The cytochrome oxidase subunit I and subunit III genes in Oenothera mitochondria
      are transcribed from identical promoter sequences.
AB  - Two loci encoding subunit III of the cytochrome oxidase (COX) in Oenothera
      mitochondria have been identified from a cDNA library of mitochondrial
      transcripts. A 657-bp sequence block upstream from the open reading frame is also
      present in the two copies of the COX subunit I gene and is presumably involved in
      homologous sequence rearrangement. The proximal points of sequence rearrangements
      are located 3 bp upstream from the COX I and 1139 bp upstream from the COX III
      initiation codons. The 5'-termini of both COX I and COX III mRNAs have been
      mapped in this common sequence confining the promoter region for the Oenothera
      mitochondrial COX I and COX III genes to the homologous sequence block.

PMID- 15981334
TI  - Common signal transduction system shared by STE2 and STE3 in haploid cells of
      Saccharomyces cerevisiae: autocrine cell-cycle arrest results from forced
      expression of STE2.
AB  - Induction of STE2 expression using the GAL1 promoter both in a wild-type MATalpha
      strain and in a MATalpha ste3 strain caused transient cell-cycle arrest and
      changes in morphology ('shmoo'-like phenotype) in a manner similar to alpha cells
      responding to alpha-factor. In addition, STE2 expressed in a MATalp[ha ste3
      mutant allowed the cell to conjugate with alpha cells but at an efficiency lower
      than that of wil-type alpha cells. This result indicates that signal(s) generated
      by alpha-factor in alpha cells can be substituted by signal(s) generated by the
      interaction of alpha-factor with the expressed STE2 product. When STE2 or STE3
      was expressed in a matalpha1 strain (insensitive to both alpha- and a-factors),
      the cell became sensitive to alpha- or a-factor, respectively, and resulted in
      morphological changes. These results suggest that STE2 and STE3 are the sole
      determinants for alpha-factor and a-factor sensitivity, respectively, in this
      strain. On the other hand, expression of STE2 in an a/alpha diploid cell did not
      affect the alpha-factor insensitive phenotype. Haploid-specific components may be
      necessary to transduce the alpha-factor signal. These results are consistent with
      the idea that STE2 encodes an alpha-factor receptor and STE3 encodes an a-factor
      receptor, and suggest that both alpha- and a-factors may generate an exchangeable
      signal(s) within haploid cells.

PMID- 15981335
TI  - The halo-opsin gene. I. Identification and isolation.
AB  - Halorhodopsin (HR), the light-driven chloride pump in halobacteria, was purified
      in the denatured as well as in the native state and chemically cleaved into
      peptide fragments. Isolation of peptide and liquid phase sequencing yielded
      approximately 20% of the halo-opsin (HO) structure in non-overlapping peptides.
      Chemically synthesized oligodeoxynucleotides corresponding to a peptide sequence
      obtained from both HR preparations were used to screen a cosmid gene bank of
      Halobacterium halobium strain L-33. A positive clone contained cosmid pAB H47
      which by subcloning and nucleotide sequencing was shown to encode at least part
      of the HO gene.

PMID- 15981336
TI  - The halo-opsin gene. II. Sequence, primary structure of halorhodopsin and
      comparison with bacteriorhodopsin.
AB  - The gene for the protein moiety of the light-driven chloride pump halorhodopsin
      (HR), hop gene, was sequenced and the primary structure of the protein derived
      thereof. The gene has a GC content of 67% and codes for 274 amino acids. A
      promoter structure, resembling that of the halobacterial 16S rRNA genes, is
      present and both a terminating stem and a loop sequence is found downstream of
      the TGA stop codon. A ribosomal binding site is located within the translated
      region. The HR protein moiety is processed at the amino terminus, as well as the
      carboxy terminus, yielding a dominant species of calculated Mr 26 961.

PMID- 15981337
TI  - Identification of silencer binding proteins from yeast: possible roles in SIR
      control and DNA replication.
AB  - The 'silent' yeast mating-type loci (HML and HMR) are repressed by sequences
      (HMLE and HMRE) located over 1 kb from their promoters which have properties
      opposite those of enhancers, and are called 'silencers'. Both silencers contain
      autonomously replicating sequences (ARS). Silencer activity requires four trans
      acting genes called SIR (silent information regulator). We have identified two
      DNA binding factors , SBF-B and SBF-E, which bind to known regulatory elements at
      HMRE. SBF-B binds to a region involved in both the silencer and ARS functions of
      HMRE, but doesn not bind to HMLE. This factor also binds to the unlinked ARS1
      element. SBF-E recognizes a sequence found at both silencers. These results
      suggest that the two silencers may be composed of different combinations of
      regulatory elements at least one of which is common to both. Neither factor
      appears to be a SIR gene product. Hence the SIR proteins may not directly
      interact with the silencer control sites.

PMID- 15981338
TI  - Genes for stable RNA in the extreme thermophile Thermoproteus tenax: introns and
      transcription signals.
AB  - To investigate gene organization and expression signals in extreme thermophilic
      archaebacteria, tRNA genes were cloned from Thermoproteus tenax. Clones for five
      tRNA species were obtained, namely for tRNAAla (TGC), tRNAAla (CGC), tRNALeu
      (CAG), tRNALeu (CAA) and tRNAMet (CAT). Three of the respective genes were
      located singly in the chromosome, the two others (tRNAAla and tRNAMet) were
      clustered but in a head to head position. Four of the genes contained intervening
      sequences, either in the classical position 3' to the anticodon (tRNAMet), or
      within the anticodon sequence (tRNALeuCAG), or in the hitherto unique position 5'
      to the anticodon within the anticodon stem region (tRNAAla). Existence of a
      transcript containing the intervening sequence was demonstrated by nuclease S1
      mapping. All tRNA genes were extremely rich in G-C basepairs of helical regions,
      a feature which may contribute to thermostability of the secondary structure. The
      start site of transcription of the 16S/23S rRNA operon and of two tRNA genes of
      Thermoproteus was determined by nuclease S1 mapping. Transcription of the tRNA
      genes initiates close to or immediately at the 5' end of the structural gene,
      that of the rRNA operon 175 bp upstream of the coding region. About 18 bp
      upstream of the transcription initiation site a conserved AT-rich sequence motif
      occurs within a fairly GC-rich intercistronic spacer. Its putative instability at
      the high growth temperature of Thermoproteus suggests a function as entry site
      for RNA polymerase.

PMID- 15981340
TI  - Is it possible to predict the average surface hydrophobicity of a protein using
      only its amino acid composition?
AB  - Hydrophobicity is one of the most important physicochemical properties of
      proteins. Moreover, it plays a fundamental role in hydrophobic interaction
      chromatography, a separation technique that, at present time, is used in most
      industrial processes for protein purification as well as in laboratory scale
      applications. Although there are many ways of assessing the hydrophobicity value
      of a protein, recently, it has been shown that the average surface hydrophobicity
      (ASH) is an important tool in the area of protein separation and purification
      particularly in protein chromatography. The ASH is calculated based on the
      hydrophobic characteristics of each class of amino acid present on the protein
      surface. The hydrophobic characteristics of the amino acids are determined by a
      scale of aminoacidic hydrophobicity. In this work, the scales of Cowan-Whittaker
      and Berggren were studied. However, to calculate the ASH, it is necessary to have
      the three-dimensional protein structure. Frequently this data does not exist, and
      the only information available is the amino acid sequence. In these cases it
      would be desirable to estimate the ASH based only on properties extracted from
      the protein sequence. It was found that it is possible to predict the ASH from a
      protein to an acceptable level for many practical applications (correlation
      coefficient > 0.8) using only the aminoacidic composition. Two predictive tools
      were built: one based on a simple linear model and the other on a neural network.
      Both tools were constructed starting from the analysis of a set of 1982 non
      redundant proteins. The linear model was able to predict the ASH for an
      independent subset with a correlation coefficient of 0.769 for the case of Cowan
      Whittaker and 0.803 for the case of Berggren. On the other hand, the neural model
      improved the results shown by the linear model obtaining correlation coefficients
      of 0.831 and 0.836, respectively. The neural model was somewhat more robust than
      the linear model particularly as it gave similar correlation coefficients for
      both hydrophobicity scales tested, moreover, the observed variabilities did not
      overcome 6.1% of the mean square error. Finally, we tested our models in a set of
      nine proteins with known retention time in hydrophobic interaction
      chromatography. We found that both models can predict this retention time with
      correlation coefficients only slightly inferior (11.5% and 5.5% for the linear
      and the neural network models, respectively) than models that use the information
      about the three-dimensional structure of proteins.

PMID- 15981339
TI  - The conformations of hirudin in solution: a study using nuclear magnetic
      resonance, distance geometry and restrained molecular dynamics.
AB  - The solution conformations of the protein hirudin have been investigated by the
      combined use of distance geometry and restained molecular dynamics calculations.
      The basis for the structure determination comprised 359 approximate inter-proton
      distance restrains and 10 phi backbone torsion angle restrains derived from
      n.m.r. measurements. It is shown that hirudin is composed of three domains: a
      central core made up of residues 3-30, 37-46 and 56-57; a protruding 'finger'
      (residues 31-36) consisting of the tip of an antiparallel beta sheet, and an
      exposed loop (residues 47-55). The structure of each individual domain is
      relatively well defined with average backbone atomic r.m.s. differences of <2 A
      between the final seven converged restrained dynamic structures and the mean
      structure obtained by averaging their coordinates. The orientation of the two
      minor domains relative to the central core, however, could not be determined as
      no long-range (i-h >5) interdomain proton-proton contacts could be observed in
      the two-dimensional nuclear Overhauser enhancement spectra. From the restrained
      molecular dynamics calculations it appears that the two minor domains exhibit
      large rigid-body motions relative to the central core.

PMID- 15981341
TI  - Stress urinary incontinence: current understanding.
AB  - Many new concepts were introduced in epidemiology, a etiopathology and treatment
      of stress urinary incontinence. This review gives a short account of these
      concepts and compares the results of commonly used treatment options with new
      ones recently introduced.

PMID- 15981342
TI  - Walking at work: a pedometer study assessing the activity levels of doctors.
AB  - BACKGROUND: The World Health Organisation cites a sedentary lifestyle as one of
      the top ten causes of morbidity and mortality worldwide.4 A recent, large-scale
      clinical study showed that brisk walking and vigorous exercise are associated
      with substantial (and similar) reductions in the incidence of coronary heart
      disease. Current guidelines suggest 10,000 steps per day as an appropriate
      activity target for healthy adults. AIMS: This study aims to assess whether
      doctors are meeting this daily walking target during working-hours, and whether
      additional out-of-hours exercise is required. METHODS: 16 doctors from St. John's
      Hospital in Livingston (comprising 4 Medical Consultants, 4 Surgical Consultants,
      4 Medical PRHOs and 4 Surgical PRHOs) each used a belt-worn pedometer to record
      all steps made during 5 consecutive day shifts. Stride length and total daily
      steps were recorded. Steps made out-with working hours were not counted. Total
      steps and hours worked were recorded at the end of each day. RESULTS: Average
      daily steps recorded were 7907 (Medical PRHOs), 5068 (Surgical PRHOs), 4822
      (Surgical Consultants) and 4647 (Medical Consultants). P values of < 0.1 were
      obtained for the variation in steps between the Medical PRHOs and both the
      Consultant Surgeons and Consultant Physicians. Distance walked per shift varied
      from 3.84 (Consultant Physicians) to 6.85 kilometres (Medical PRHOs). CONCLUSION:
      Walking at work does provide a substantial proportion of a doctor's recommended
      daily activity quota. However, it is still necessary to engage in additional, out
      of-hours exercise in order to consistently meet the current recommendations for
      physical exercise.

PMID- 15981343
TI  - Acute hemolytic transfusion reaction secondary to anti-Fy3.
AB  - A hemolytic transfusion reaction due to anti-Fy3 is reported in an African
      American patient with no history of sickle cell disease. This 82-year-old African
      American woman received two units of RBCs for anemia (Hab 7 g/dL) on admission
      for a left hip fracture. On hospital Day 7, the patient underwent left hip
      endoprosthesis surgery; she received two units of RBCs on the second
      postoperative day due to Hb of 6.1 g/dL. Her urine was dark during surgery and
      postoperatively. Her posttransfusion plasma was red. Her Hb dropped from 8.4 to
      6.4 g/dL over 24 hours after the transfusion. Her total bilirubin rose to 4.0
      mg/dL, with and LDH value of 1558 U/L and a haptoglobin of 10.9 mg/dL. Both the
      antibody detection test and the DAT were positive. An anti-Fy3 was identified in
      the serum and in the eluate. To the best of our knowledge, this is the first case
      of acute intravascular hemolysis due to anti-Fy3 in a patient without sickle cell
      disease.

PMID- 15981344
TI  - Interview with the LDA 2005-2006 President, Dr. Timothy R. Perry.

PMID- 15981345
TI  - A national clinical licensing examination--the time has come.

PMID- 15981346
TI  - Louisiana Dental Sealant Initiative plans to give kids a smile.

PMID- 15981347
TI  - Maximize your HSA tax benefits.

PMID- 15981348
TI  - Milk removal from the breast.

PMID- 15981349
TI  - Latch and the fear response: overcoming an obstacle to successful breastfeeding.
AB  - A cringe response, born of fear of anticipated nipple pain, creates behaviours
      that undermine comfortable latch of baby at breast, resulting in the pain th
      women feared. Fear is an important response in human survival but sometimes the
      behaviours resulting from the fear are inappropriate. This case study discusses
      the psychological processes and specific physical responses observed in a woman
      who is experiencing nipple pain during breastfeeding. It describes steps that can
      be taken to assist the mother in identifying what she is doing, educating her
      about the processes involved, and providing her with strategies to override the
      inappropriate response.

PMID- 15981350
TI  - Literature research: aims and design of systematic reviews.

PMID- 15981351
TI  - Manual therapy is more efficient than exercise therapy for osteoarthritis of the
      hip.

PMID- 15981352
TI  - The last frontier: isolation and Aboriginal health.
AB  - Using the evidence of articles on Native and Inuit health in Canadian medical and
      public health periodicals, this paper will show that medical professionals
      defined Aboriginal health in terms of isolation. Notions of isolation influenced
      how Aboriginal bodies were depicted as "primitive" and "susceptible," while
      images of empty, isolated territory inspired a vision for expanded federal
      services. These services were provided in part in the hopes that health programs
      would assist national goals to integrate "isolated" Aboriginal people as
      citizens. Last, a discourse on isolation served to sanctify those medical
      professionals who worked with native and Inuit people.

PMID- 15981353
TI  - Warm-up exercise prevents acute knee and ankle injuries in young handball
      players.

PMID- 15981354
TI  - The changing face of hospital care in the 18th-century Upper Normandy: the
      hospital of Caudebec and the arrival of "paying inmates" (1693-1789).
AB  - This article questions the view that hospitals in early modern France were static
      and inflexible institutions. The small-town hospital of Caudebec in present-day
      Upper Normandy underwent three major transformations during the course of the
      18th century. Founded in 1693 as a "local" hospital, the institution was
      designated as an hopital general in 1724 and began incarcerating beggars and
      vagrants. Later, with the influx of sick and wounded soldiers brought on by the
      Seven Years' War, the hospital took on the functions of a small military
      hospital. On the eve of the French Revolution, the hospital's "civilian"
      population contained a growing number of individuals who offered to pay for the
      cost of their care. The arrival of these groups of "paying inmates" shows that
      the Caudebec hospital was capable of adapting to changing circumstances and was
      able to respond to the new priorities of the State.

PMID- 15981355
TI  - Practical ethics. Guilt by association?

PMID- 15981356
TI  - Quarantine in question: the 1913 investigation at William Head, B.C.
AB  - The Canadian government operated a quarantine station at William Head B.C. from
      1881 to 1958. In the spring of 1913, a ship arriving from the Orient was detained
      because of smallpox. Subsequently, the station's medical inspector, Dr. A. T.
      Watt, became the subject of a Royal Commission of Inquiry established to
      investigate his medical and administrative practices. That summer Watt committed
      suicide, but was posthumously exonerated from all the charges. This paper
      explores the conflicting class and racial questions that arose from this incident
      and the political reactions of those involved including the detainees, the
      government, and the media.

PMID- 15981358
TI  - Artifacts and Archives/Archives et artefacts de la pratique medicale. The origin
      of the Canadian Cancer Society.
AB  - In 1929, when the Saskatchewan Medical Association created a Cancer Committee,
      the major achievement of the Committee was the establishment of the first
      government supported comprehensive provincial cancer control program in Canada.
      The report also proposed the establishment of a voluntary medical-lay Canadian
      Society for the Control of Cancer. As the comprehensive cancer control concept
      spread across Canada within the provinicial medical associations and provinicials
      governments, the Canadian Medical Association (CMA), represented by Dr. John S.
      McEachern, took up the cause of promoting such a voluntary cancer organization.
      Initially the idea developed slowly but, in 1935, gained momentum when the
      Governor General, the Earl of Bessborough, initiated The King George V Silver
      Jubilee Cancer Fund for Canada and financial support for such a project became a
      possibility. The focus of this paper is on McEachern's shepherding of the
      voluntary cancer society idea within the CMA and the convoluted path which led to
      the provision of financial support for the project by the Trustees of the King
      George V Cancer Fund. The Canadian Society of the Control of Cancer, later
      renamed the Canadian Cancer Society, was created by Letters Patent on 28 March
      1938.

PMID- 15981357
TI  - Dropped head: an unusual presentation of dermatomyositis.

PMID- 15981359
TI  - ["Dedi clysterem purgantem" - Haller and the medicine of childhood (1731-1736)].
AB  - Albert Haller practiced medicine in Berne before being appointed Professor of
      Anatomy and Botany at the University of Gottingen. From 1731 to 1736, he kept a
      journal detailing the treatments he prescribed to his approximately 300 patients,
      63 of whom were children and adolescents. The journal noted 580 pediatric
      consultations and detailed the ailments, their progression and applied therapies,
      allowing the reconstruction of case histories, some of which extended for several
      years. Through analysis of this data, we attempt to answer the questions such as:
      What diseases led parents to ask for medical interventions for their children?
      What were the age cohorts of the group of young patients? At one point did Haller
      perceive as serious their statements and symptoms/ How frequent were
      consultations? What were the prescribed therapies? Did he base his conclusions on
      the value of a child's life attributed by physicians and society of the period?

PMID- 15981360
TI  - Hospital computer keyboards and keyboard covers harbor potentially harmful
      bacteria.

PMID- 15981361
TI  - Evaluation of a clinically positive neck after 5000 cGy.

PMID- 15981362
TI  - HIPAA compliance soars, but health information exchanges will present big
      challenges.

PMID- 15981363
TI  - History of 'Spiritist madness' in Brazil.
AB  - Spiritism is widely accepted in Brazil and influences psychiatric practice,
      especially through religious-oriented hospitals. However, during the first half
      of the twentieth century it was considered an important cause of mental illness.
      This paper first reviews opinions on 'Spiritist madness', written by the most
      eminent psychiatrists of the time, and then discusses the epistemological factors
      that have contributed to the conflict between medicine and Spiritism. We
      critically examine the appropriateness of the methods used in the debates, and
      how this has led to inferences about associations and causal relationships.

PMID- 15981364
TI  - Service utilization in 1896 and 1996: morbidity and mortality data from North
      Wales.
AB  - The 1896 and 1996 populations of North-West Wales are similar in number, ethnic
      and social mix and rurality, enabling a study of the comparative prevalence of
      service utilization, as well as the morbidity and mortality associated with
      mental illness in 1894-96 and 1996. The 1996 data reveal a 15 times greater
      prevalence of admissions for all diagnoses, and three times greater prevalence of
      admissions by detention, compared with 1896. Patients now spend more time in a
      service bed than they did 100 years ago. Death as a direct consequence of mental
      illness is commoner now than 100 years ago. There is therefore a major
      disjunction between the rhetoric and the reality of mental health service
      utilization. General factors related to changing health care and expectations and
      specific factors linked to the mental health appear to have led to an increased
      rate of service utilization in the modern period.

PMID- 15981365
TI  - Psychological injury in the two World Wars: changing concepts and terms in German
      psychiatry.
AB  - This paper describes how German psychiatrists in two World Wars treated
      psychologically injured soldiers, and the concepts of related illnesses which
      they developed. The literature is reviewed, and symptomatolgy of patients and
      therapeutic practice in the wars are compared. By 1916 German psychiatrists had
      already established a concept of illness that continued to be used until World
      War II and beyond, albeit with a changing terminology. The vague term 'war
      neurosis' was commonly used, but covered different, partly overlapping concepts.
      Psychiatrists considered the disorder as a psychogenetic reaction based on an
      individual predisposition and denied a causal link between the experience of war
      and subsequent psychopathology. It may be concluded that psychiatrists developed
      theoretical models and practical treatment methods in a manner that met the
      social and military requirements of the time.

PMID- 15981366
TI  - Logics of delusion.
AB  - Delusion represents an exceptional test case for the principal categories of
      common sense and philosophical thought, such as 'reason', 'truth' and 'reality'.
      Via an engagement with the legacy of Freud and the most discussed results of
      twentieth-century psychiatry, my aim will be to analyse its paradoxical forms and
      to shed light on the logics that underlie and orient its specific modalities of
      temporalization, conceptualization and argumentation. Delusion, then, has
      traditionally been presented as synonymous with irrationality (absurdity,
      groundlessness, error, chaos), whereas by contrast its mirror image, reason, has
      been defined in terms of evidence, demonstrability, truth and order. I will
      analyse and contrast their paradoxical definitions.

PMID- 15981367
TI  - Cox's chair: 'a moral and a medical mean in the treatment of maniacs'.
AB  - Two hundred years ago Joseph Cox published his book on the treatment of insanity.
      His novel technique was rotating the body in a specially designed chair.
      Initially modest and later extravagant claims were made for the therapeutic
      benefit of 'Cox's chair'. It was widely adopted in Europe in the first decades of
      the nineteenth century, but lost favour thereafter. Its benefits have proved to
      be scientific rather than medical because it was adopted by students of the
      senses to investigate vertigo; a century later it re-emerged as the Barany chair
      for the clinical assessment of vestibular function. The legacy of Cox's chair,
      and its related treatment of swinging, are to be found in funfairs throughout the
      world.

PMID- 15981368
TI  - A bogus Benjamin Rush quote: contribution to the history of pharmacracy.
AB  - Benjamin Rush (1746-1813), the 'father' of American psychiatry, is perhaps best
      known as the inventor of the 'tranquilizing chair'. In recent decades, political
      and psychiatric activists have attributed a quotation to him in which he
      allegedly warned: 'To restrict the art of healing to one class of men and deny
      equal privileges to others will constitute the Bastille of medical science.' The
      source of this quotation cannot be found, and Rush's remarks about 'medical
      despotism' are inconsistent with the body of his work. Other examples are cited
      to illustrate the thesis that false attributions, used to support and advance
      particular ideological causes, are remarkably resistant to efforts at correction.

PMID- 15981369
TI  - Some traits of Norwegian pre-medical social reactions to madness.
AB  - A three-phase development of institutions for the mad is suggested, mainly on the
      basis of studies in Norwegian legal history archives. The discrepancy between two
      reports of 1812 and 1828 indicates a different watershed in the Norwegian history
      of psychiatry from the mythical royal decree of 1736.

PMID- 15981370
TI  - Lobotomy in Norwegian psychiatry.
AB  - Lobotomy is still a hidden chapter in the history of Norwegian psychiatry. The
      main reasons, which are discussed here, may have been the role of Ornulv Odegard
      at Gaustad Hospital in Oslo and the links between health authorities and the
      power elite in Norwegian psychiatry.

PMID- 15981371
TI  - The cemetary associated with Leyme Mental Hospital.
AB  - A detailed study of a cemetary attached to a provincial psychiatric hospital
      underscores its resemblance to military and Anglo-Saxon burial grounds. It is a
      sad reminder of the isolation and abandonment of many patients in French asylums
      up to the middle of the twentieth century.

PMID- 15981372
TI  - Excerpt from Medicinische Psychologie oder Physiologie der Seele by Dr Rudolph
      Hermann Lotze.
AB  - Hermann Lotze (1817-81) is a neglected figure in the history of psychiatry
      although it has been claimed that his early views were influential, for example,
      on the young Griesinger. Trained as a physician, psychologist and philosopher he
      saw better than many the impending epistemological crisis that was to affect
      disciplines such as psychology and medical psychology as they were being taken
      over by the natural sciences. The problem he endeavoured to resolve was double
      headed. On the one hand, Lotze believed that the mechanisms proposed by
      physiology and other relevant natural sciences were essential to the explanation
      of human behaviour provided that its meaning and context were respected; on the
      other, he wanted to do away with the mysterious (metaphysical) explanations such
      as 'vital force' which in his time were still popular in biology. The solutions
      he eventually offered can understandably be seen as a weak compromise and one
      which statisfied no one. Materialists a outrance such as Vogt, Buchner, Lange and
      Ribot though he was too 'metaphysical'; spiritualist philosophers believed that
      he had surrendered too much to biology. It is likely that Lotze remained, in
      fact, a metaphysician as can be ascertained by studying his concept of Seele
      (soul, mind) into which he packed enough furniture to make many believe that he
      was an idealist thinker. This paper discusses some of these issues and justifies
      the choice of classic text, namely, Lotze's illuminating Introduction to his book
      Medicinische Psychologie oder Physiologie der Seele.

PMID- 15981373
TI  - Medico-historical review of drug Kustha.
AB  - Kustha is well known for its cures since ancient times. Atharvaveda considers
      this as a potent plant next to Soma (a divine plant) in curing several diseases.
      It is also called Takmanashana (which cures fevers) in Atharvaveda. It grows in
      Himalayas and Kasmir. In Ayurveda, root of Kustha is used for fevers, skin
      diseases, headache etc. Almost all Nighantus carry the description of Kustha with
      several synonyms. Some scholars consider two varieties of Kustha i.e. sweetish
      and bitter, but one with bitter taste is the real Kustha. Pushkarmool (Inula
      recemosa Hook.f.) is available in the market as sweet variety of Kustha. Thus its
      medico-historical importance and other details have been presented in this
      article.

PMID- 15981374
TI  - A comparative study of Prameha Roga from the Brihatrayee.
AB  - The study of this Prameha Roga reveals the rich knowledge of the Ayurveda
      developed since the time immemorial. Although descriptions of this disease are
      scattered in different classics of Ayurveda but here importance has been given to
      Brihatrayee. The aim and object of this paper review the well documented concept
      of the Ayurveda about the Prameha Roga as the trend of diabetes is increasing day
      by day in the society and is very difficult to prevent and manage owing to its
      complexity. The Ayurvedic concept of this Roga information on the subject
      regarding classification, characteristics, features etc. has been also made in
      this paper. This article highlights the wisdom of ancient Indian literature and
      some historical view of the disease i.e. Prameha Roga or Diabetes Mellitus.

PMID- 15981375
TI  - Ayurvedic literature in Urdu part-III.
AB  - The present article is the continuation of the second part of the previous work
      published with the same title in the Bulletin of Indian Institute of History of
      medicine, Vol. XXIX. No. 2 in 1999. This work has ben initiated to introduce the
      books written in recent past, the period in which Urdu language had a prominent
      role in preserving the knowledge of old arts and sciences.

PMID- 15981377
TI  - History of the stethoscope an overview.
AB  - The stethoscope represents the physician perhaps more than any other symbol,
      except the shaft of Aesculpaius of Kos Island, Greece (birthplace of Hippocrates)
      - the god of Temple medicine of the Greek antiquity. In early modern ear of the
      19th century, it was spectacular product of developing synthetic chemical
      technology which was progressively used in its making. It was a remarkable
      addition to the clinico-diagnostic armamentarium of doctors. Laennec paved the
      way in 1819, and since then it has been a long march of continuous innovative
      development supplying for the demand of relevant auscultatory bedside tool to
      examine different medical conditions.

PMID- 15981376
TI  - A historical perspective on menopause and menopausal age.
AB  - Earliest known references to menopause have been very scarce. Aristotle referred
      to age at menopause being 40 years. A French physician coined the term menopause
      in 1821. Medical interest in menopause increased considerably in mid 19th
      century. In 1930s people started describing it as a deficiency disease.
      Consequently, various replenishment therapies were advocated eg. testicular
      juice, crushed ovaries of animals. In 1970s medicalization of menopause was
      complete. Menopausal symptoms were ascribed to estrogen deficiency and estrogen
      (hormone) replacement therapy was exhorted as the ultimate liberation of middle
      aged women. Synthetic estrogen was developed in 1938. Medical industry
      (Pharmaceuticals) entered the scenario of menopause in a big way and dominated
      the center stage. In 1970s International Menopause Society was established. First
      International Congress on Menopause was also organized in Paris, France in 1976.
      Various countries have formed national societies on menopause. Symptomatology of
      menopause differs in different ares of the world e.g In West - hot flush, in
      Japan shoulder pain and in India low vision are the hallmarks of menopause. HRT
      use rate is high in West while it is low or negligible in countries like India.
      Age at menopause is also higher in West as compared to the range of 45-47 years
      in developing countries like India. Historically also a lower age at menopause
      was range documented in earlier times. This rose to the range of 50-51 years in
      the present era.Overall, women in western countries view menopause negatively.
      This is contrasted with a positive outlook towards menopause in a developing
      country like India.

PMID- 15981378
TI  - Flora of the Holy Bible part I - fruits.
AB  - Holy Bible described several plants and the authentication of certain Biblical
      flora is still in debate. In this present paper, attempts are being made to
      workout the correct botanical identity of certain plants based on the description
      mentioned in the Bible. Bible is a genuinely documented book everything mentioned
      in the Bible has a great significance. Present study is undertaken with a view to
      evaluate the biblical flora in correlation with the present day knowledge
      especially with the Ayurvedic system of medicine.

PMID- 15981379
TI  - Historical survey of wound healing.
AB  - The response of living tissues to injury forms the foundation of all surgical
      practices. Indeed, from the historical point of view, tissue injury or Vrana or
      wound and its sequelae have participated in cure of most of the general medical
      problems from the days of Susruta till date. The earlier medical literatures
      extensively considered wound care as based on instinctive remedies but on the
      other hand, the present concepts cogitate healing of wound based on visual
      observations. Basic perception of wound healing only in its interpretation, which
      has varied from civilization to civilization. There are various methods for
      treating of wounds and have since been passed over by ancient humans to today's
      modern surgeons. Therefore, it is very essential to know the historical aspects
      of Vrana and its Ropana since the beginning of the tear of medicine as compare to
      wound and it's healing from the modern point of view. On the basis of above said
      facts an attempt has been made to explore the historical background of and
      healing in present paper.

PMID- 15981380
TI  - The medical practice of the sexed body: women, men and disease in Britain , circa
      1600-1740.
AB  - Although it has been widely argued that pre-Enlightenment western medicine
      ascribed to a one-sex (male) model of the body, this theory has never been
      evaluated in terms of medical practice. This article seeks to determine the
      usefulness of such a model for early modern Britain, circa 1600-1740, by
      examining how medical practitioners responded to three common illnesses that
      afflicted both male and female patients: venereal disease, smallpox, and malaria.
      It concludes that, despite a number of similarities, medical treatment of such
      illnesses was marked by important differences which were based upon the sex of
      the patient. Due to its unique physiological functions (vaginal discharge,
      menstruation, pregnancy, and lactation), the female body was considered by
      practitioners to be capable of manifesting, transmitting, and responding to
      disease and treatment in ways that the male body could not. This awareness
      provided practitioners with additional reasons to monitor, and alter, medical
      treatment in their female patients. In fact, the different constitutions of men
      and women meant that the patient body was much more complex than the theory of a
      one-sex model suggests. Furthermore, differences in medical treatment were
      influenced by age, a variable which was inexorably linked to physiological
      changes in the 'sexed' body.

PMID- 15981381
TI  - 'The true assistant to the obstetrician': state regulation and the legal
      protection of midwives in nineteenth-century Prussia.
AB  - In recent years, historians of eighteenth- and nineteenth-century European
      midwifery have drawn attention to the great differences between midwives'
      experiences in England and the United States, where obstetricians succeeded by
      and large in displacing female practitioners, and midwives' experiences on the
      continent, where their fate was far more varied. While some countries witnessed
      the decline of midwives, in many others they were licensed and integrated into a
      government-sanctioned medical hierarchy. Scholars have disagreed, however, on how
      to evaluate the government's role in regulating midwives. Some have been
      critical, portraying midwives as victims of an alliance between the State and
      elite physicians who sought to place all other practitioners under their control.
      Others have cast midwives as beneficiaries of the State's protectionist policies,
      emphasizing their success in withstanding physicians' attempts to eliminate them
      entirely. Whilst these different interpretative models may reflect some regional
      variations, this article suggests that, in many cases, midwives both lost and won
      simultaneously: as State employees they lost much of their independence, but in
      exchange they gained protection not only from elite physicians, but also from
      unlicensed practitioners, who posed every bit as much of a threat.

PMID- 15981382
TI  - Sanitary policing and the local state, 1873-1874: a statistical study of English
      and Welsh towns.
AB  - This article examines local sanitary policing in extra-metropolitan English and
      Welsh towns and cities in the period 1873-4. It combines two parliamentary
      returns, one focusing on the appointments by towns of sanitary officers
      (inspectors of nuisances and medical officers), the other listing the number of
      nuisance cases and modes of resolutions. The article uses these databases to
      examine the identification of nuisances in terms of region, town type, mode of
      government, population, and salary of inspector. It considers also the effects of
      tenure and job security on nuisances identification, the effects of town wealth,
      and differences in the resolution of nuisance allegations by town type and
      region. The article shows a remarkable and perhaps unexpected sanitary activism,
      but also a considerable variability by region, town size, and town type.

PMID- 15981383
TI  - Coming up for air: experts, employers, and workers in campaigns to compensate
      silicosis sufferers in Britain, 1918-1939.
AB  - Government regulation of dangerous trades and the compensation of those injured
      by their work remains a matter of considerable debate among medical historians.
      Trade unions have frequently been criticized for pursuing financial awards for
      their members rather than demanding improvements in health and safety at the
      workplace. This article examines the neglected subject of silicosis injuries in
      Britain from the time when the first legislation was passed for compensation of
      those suffering from the harmful affects of silica dust in 1918 to the outbreak
      of war in 1939, when a major new study was under way which would transform the
      scientific understanding and the legal compensation of those who were diagnosed
      as being ill with pneumoconiosis. It is argued that in framing legislation from
      compensation, politicians and their civil servants sought to retain the legal
      framework created in 1897-1906 and developed a model of industrial insurance
      which depended to a large extent on a co-operative relationship with leading
      employers. Medical scientists identified silica as a uniquely hazardous agent in
      workers' lung disease, which emphasizing the specialist knowledge required for
      its diagnosis. One remarkable feature of the selective compensation schemes
      devised after 1918 was the reliance on geological rather than pathological
      evidence to prove compensation rights as well as strict employment limits on
      those eligible to claim. only the campaigning of labour organizations and
      persistent evidence of lung disease among anthracite coal miners led to a
      significant relaxation of compensation rules in 1934 and the fresh scientific
      investigation which transformed the medical understanding of respiratory illness
      among industrial workers.

PMID- 15981384
TI  - Continuation of benefit payments to certain individuals who are participating in
      a program of vocational rehabilitation services, employment services, or other
      support services. Final rule.
AB  - We are publishing final rules that amend the rules for the continuation of
      disability benefit payments under titles II and XVI of the Social Security Act
      (the Act) to certain individuals who recover medically while participating in an
      appropriate vocational rehabilitation (VR) program with a State vocational
      rehabilitation agency. We are amending these rules to conform with statutory
      amendments that extend eligibility for these continued benefit payments to
      certain individuals who recover medically while participating in an appropriate
      program of services. These include individuals participating in the Ticket to
      Work and Self-Sufficiency Program or another program of vocational rehabilitation
      services, employment services, or other support services approved by the
      Commissioner of Social Security. We are also extending eligibility for these
      continued benefit payments to students age 18 through 21 who recover medically,
      or whose disability is determined to have ended as a result of an age-18
      redetermination, while participating in an individualized education program
      developed under the Individuals with Disabilities Education Act with an
      appropriate provider of services. Providers of services we may approve include a
      public or private organization with expertise in the delivery or coordination of
      vocational rehabilitation services, employment services, or other support
      services; or a public, private or parochial school that provides or coordinates a
      program of vocational rehabilitation services, employment services, or other
      support services carried out under an individualized program or plan.

PMID- 15981385
TI  - The politics of school sex education policy in England and Wales from the 1940s
      to the 1960s.
AB  - This article explores the political history of school sex education policy in
      England and Wales. Focusing on the period from the 1940s to the 1960s, it shows
      how sex education developed as a controversial political issue through an
      analysis of the differing institutional cultures and agendas of health and
      education administrators. The article argues that serious consideration of school
      sex education by central government was first prompted by concern about venereal
      disease during the Second World War. Thereafter, two groups of actors emerged
      with conflicting ideas about the role of government in prescribing school sex
      education. The medical establishment, including the Ministry of Health, was
      broadly supportive of a national policy, whereas the Department of Education,
      which had ultimate responsibility for any such policy in schools, sought to avoid
      decision-making about the issue. The article explores how a public health
      consensus on sex education developed and then explains why the Department of
      Education resisted this consensus.

PMID- 15981386
TI  - The English patient in post-colonial perspective, or practising surgery on the
      poms.
AB  - Drawing on interviews with Australasian surgeons who trained in the 1950s and
      1960s, this article discusses where, and on whom, they practised the manual
      skills involved in surgery, In the twentieth century, elite Australasian surgeons
      emphasized the importance of the science of surgery and the lengthy experience
      needed to acquire surgical judgement, and these concerns are reflected in the
      accreditation procedures adopted by the Royal Australasian College of Surgeons.
      However, trainee surgeons also ha to acquire th manual skills that they needed in
      the operating theatre. The rhetoric of training emphasized the intellectual
      skills needed in surgery, but in reality the manual skills remained important,
      and there was also a fascination with the drama and stress involved in operating.
      In this era, British and Australasian surgical training were closely linked and
      many Australasian surgeons gained significant cutting experience in Britain.

PMID- 15981387
TI  - Etanercept: new indication. For ankylosing spondylitis: another option.
AB  - (1) Nonsteroidal antiinflammatory drugs (NSAIDs) are the standard drug treatments
      in ankylosing spondylitis. Infliximab, a TNF-alpha antagonist immunosuppressant,
      is reserved for severely ill patients for whom standard treatment has failed.
      Infliximab is provided as an infusion and requires close monitoring. (2)
      Etanercept, another TNF-alpha antagonist immunosuppressant, was recently approved
      in Europe for the treatment of ankylosing spondylitis. (3) In three double-blind
      placebo-controlled trials (40 patients treated for 4 months, 277 patients treated
      for 6 months, 84 patients treated for 3 months), between 60% and 80% of patients
      on etanercept "responded" to treatment, with at least a 20% improvement in an
      endpoint combining various symptoms of ankylosing spondylitis. There are no
      direct comparisons to show whether this short-term effect differs tangibly from
      that of infliximab. (4) Etanercept has the same adverse effect profile as
      infliximab. In particular, both immunosuppressants increase the risk of
      tuberculosis and opportunistic infections. Risks associated with long-term
      immunosuppression, such as malignancy, are poorly understood: postmarketing
      follow-up data are only available for 6 years. (5) As of 7 December 2004, no
      detailed results had been published on randomised trials comparing etanercept
      with other recently approved immunosuppressants used to treat ankylosing
      spondylitis. (6) Etanercept is administered subcutaneously twice a week, on an
      outpatient basis, for the treatment of ankylosing spondylitis as well as
      psoriatic rheumatism. In contrast, infliximab is infused every 6 to 8 weeks and
      must be administered in hospital. (7) Etanercept is an alternative to infliximab
      as a treatment option for patients with ankylosing spondylitis who have failed to
      respond to standard treatments.

PMID- 15981388
TI  - [The pendulum and the mortar. Some pharmacist deviners and particularly Gabriel
      Lesourd].
AB  - At the beginning of the 1930s, many French doctors and pharmacists practised
      dowsing. Some adhered to the 'Association des amis de la radiesthesie'. It was in
      particular the case of Gabriel Lesourd (1890-1976), owner of the famous "Tisane
      du Cure de Deuil".

PMID- 15981389
TI  - Bortezomib: new drug. A last resort in myeloma: modest efficacy, major risks.
AB  - (1) First-line treatment of multiple myeloma depends first and foremost on the
      patient's age. There is no standard treatment for relapses and the median
      survival time after the first relapse is only 12 to 15 months. (2) Bortezomib, a
      cytotoxic agent, inhibits the 26S proteasome involved in protein breakdown in
      mammalian cells. It is licensed for use in myeloma after multiple treatment
      failure. (3) Three dose-finding studies showed some effects of 1 mg/m2 and 1.3
      mg/m2 bortezomib administered twice a week for two weeks, with each course
      followed by a 10-day treatment-free period. It is not known whether 1.3 mg/m2 is
      more effective than 1 mg/m2. (4) In a non comparative trial that included 202
      patients with multidrug-resistant myeloma, progression-free survival time
      increased to a median of 6.6 months (compared to 3.3 months after previous
      relapses), and the median overall survival time was 7 months in the 75% of
      patients who did not respond and more than 15 months in the 25% of responders.
      However, given the heterogeneous nature of the study population the evidence from
      this trial is rather weak. (5) An unblinded comparative trial including 54
      patients failed to show whether bortezomib 1.3 mg/m2 was more effective than
      bortezomib 1 mg/m2 in terms of clinical outcome. Another comparative trial
      including 669 patients indicated that bortezomib was more effective than
      dexamethasone in terms of the median time to disease progression (5.7 months
      versus 3.6 months). (6) Animal studies indicate that bortezomib is cardiotoxic
      and neurotoxic, and that the interval between the maximal tolerated dose and the
      fatal dose is very small. Experience with bortezomib use is too limited to know
      the possible clinical repercussions of these experimental findings. (7) Adverse
      effects were frequent and varied in clinical trials. They included fatigue,
      nausea and vomiting, diarrhea, anemia, thrombocytopenia and peripheral
      neuropathies. They affected 30% to 60% of patients overall, and were severe in
      about 10% to 20% of patients. Other adverse effects included hypotension, fever,
      headache, pain and dehydration. (8) Bortezomib is metabolised by cytochrome P 450
      isoenzyme 3A4, and this implies a high risk of drug-drug interactions. (9) Each
      vial of bortezomib contains more of the drug than is needed for one injection.
      This is not only wasteful, but also carries a risk of overdosing, with
      potentially serious consequences, should the entire contents be injected by
      mistake. (10) Bortezomib may be used as a last resort in some patients with
      multiple myeloma, but the individual risk-benefit balance must be carefully
      weighed in each case.

PMID- 15981390
TI  - Depressed? New York screens for people at risk.

PMID- 15981391
TI  - [Charles-Henri Fialon (1846-1933), creator of the Museum of the Faculty of
      Pharmacy of Paris. His family and professional life].
AB  - Henri Fialon was pharmacist in 1871, and worked in the family apothecary, at
      Rueil near Paris. At 46 years, he stopped his pharmaceutical activity, and livre
      quietly, being specially interested by the ancient pharmaceutical pots. He
      realized a very important collection, which he gave to the French Society of
      Pharmaceutical History. A museum was installed at the Faculty of Pharmacy of
      Paris which is presently in the Guillaume Valette Gallery and contains more than
      500 pieces.

PMID- 15981392
TI  - Sponsor of stem cell bill says Senate could override a veto.

PMID- 15981393
TI  - Medical schools found to vary in their drug-testing standards.

PMID- 15981394
TI  - Schiavo autopsy says brain withered, was untreatable; Florida woman's collapse in
      1990 is still a mystery.

PMID- 15981395
TI  - Many seeking one final say on end of life.

PMID- 15981396
TI  - F.D.A. panel approves heart remedy for blacks.

PMID- 15981397
TI  - Deaths and a doctor's past transfix Australians.

PMID- 15981398
TI  - Topical retinoids during pregnancy (continued).
AB  - (1) In 1998 several cases of malformations similar to those induced by oral
      retinoids were reported in children exposed in utero to topical retinoids
      (adapalene and tretinoin). The results of two somewhat flawed epidemiological
      studies were reassuring. (2) New cases of birth defects were subsequently
      reported in children exposed in utero to topical tretinoin. (3) Epidemiological
      data are still scant and unconvincing: they neither confirm this risk nor rule it
      out completely. (4) It is best to avoid using topical retinoids altogether in
      early pregnancy. Women of child-bearing age must be fully informed of the risks
      and the importance of effective contraception. This also applies to patients with
      moderate forms of psoriasis, for which topical tazaroten is indicated.

PMID- 15981399
TI  - Bill allows sales of pill over counter: broader distribution of after-sex pill.

PMID- 15981400
TI  - F.D.A. approves a heart drug for African-Americans.

PMID- 15981401
TI  - [Analysis of frontispieces in seventeenth-century books from the Rouen libraries
      collections].
AB  - In the seventeenth century books the frontispieces generally epitomize in a
      single engraving of the thought of the author. After a short review of the Rouen
      libraries collections on which this study is based, five frontispieces with
      different set of themes are analysed: the ordering of a chemist's shop by Jean de
      Renou, the tribute paid to the Ancients by bauhin, teh Fortune, Time and Wisdom
      allegories represented in the works of Dalechamp, the allegory of the Royal
      pharmacopoeia by Moyse Charas and the Song of Solomon by Clusius. In conclusion,
      we will wonder about the possible understanding of the chemist at the time,
      facing these coded pictures.

PMID- 15981402
TI  - Drugs tested on HIV-positive foster children; Hill investigates ethical questions
      raised by 1990s trials in Maryland, elsewhere.

PMID- 15981403
TI  - Many scientists admit to misconduct: degrees of deception vary in poll;
      researchers say findings could hurt the field.

PMID- 15981404
TI  - Inside stricken mother, a race between life and death; cancer that felled woman
      now threatens fetus.

PMID- 15981405
TI  - [New research on the short affections of professor Heckel (1843-1916) at the
      newly created superior school of pharmacy in Nancy, between 1873 and 1876].
AB  - When the school of pharmacy was transferred from Strasbourg to Nancy in 1872, the
      chair of natural history was unoccupied and it remained initially in this
      position. First, the professor of faculty of medicine was designed to teach, but
      the importance of a pharmacist appeared rapidly. Edouard Marie Heckel, then
      temporary fellow at the school of Montpellier, was chosen and appointed in March
      1873. We do not know for 1874, but he came again in 1875, and became professor.
      But hardly nominated, he went to Grenoble... During these years, he participated
      actively in university and pharmaceutical activities, and he begun with professor
      Schlagdenhauffen a durable and fruitful scientific collaboration. The presence in
      Nancy of professor Heckel shows some of the qualities that explain his splendid
      university career some years later in Marseille, and give an example of the
      difficulties initially encountered by the school of pharmacy of Nancy.

PMID- 15981406
TI  - [The sale of mineral waters by the pharmacists].
AB  - In May, 1605, King Henri IV established the first national regulation of water in
      France. Mineral waters were considered as therapeutic, so pharmacists were
      expected to sell them. In 1823, pharmacists obtained a relative independence to
      sell mineral waters. Some of them became spring operators. In 1964, the
      bottling's licence obliged them to modernize their installations. Some of them
      abandoned. Gradually, mineral waters arrived in supermarkets and disappeared from
      pharmacies. Since 1980, mineral waters are not considered any more as
      therapeutic. They are now only good for the health.

PMID- 15981407
TI  - Human embryonic stem cells: an introduction.

PMID- 15981408
TI  - Cox-2 inhibitors: still no decisive action.
AB  - (1) Evidence that the Cox-2 inhibitors have severe cardiovascular adverse effects
      continues to accumulate, including an increase in overall mortality in several
      trials of rofecoxib. (2) Yet regulatory agencies on both sides of the Atlantic
      have so far only taken half-measures, issuing new contraindications and warnings
      that complicate matters for prescribers (but not for the companies concerned),
      and leave patients exposed to significant dangers.

PMID- 15981409
TI  - Studies on biosynthetic genes and enzymes of isoprenoids produced by
      actinomycetes.
AB  - Most Streptomyces strains are equipped with only the 2-C-methyl-D-erythritol 4
      phosphate (MEP) pathway for the formation of isopentenyl diphosphate, a common
      precursor of isoprenoids. In addition to this pathway, some Streptomyces strains
      possess the mevalonate (MV) pathway via which isoprenoid antibiotics are
      produced. We have recently cloned and analyzed the MV pathway gene clusters and
      their flanking regions from terpentecin, BE-40644, and furaquinocin A producers.
      All these clusters contained genes coding for mevalonate kinase, mevalonate
      diphosphate decarboxylase, phosphomevalonate kinase, type 2 IPP isomerase, HMG
      CoA reductase, and HMG-CoA synthase. The order of each of the open reading frames
      (ORFs) is also the same, and the respective homologous ORFs show more than 70%
      amino acid identity with each other. In contrast to these conservative gene
      organizations, the biosynthetic genes of terpentecin, BE-40644, and furaquinocin
      A were located just upstream and/or downstream of the MV pathway gene cluster.
      These facts suggested that all the actinomycete strains possessing both the MV
      and MEP pathways produce isoprenoid compounds and the biosynthetic genes of one
      of these isoprenoids usually exist adjacent to the MV pathway gene cluster.
      Therefore, when the presence of the MV cluster is detected by molecular genetic
      techniques, isoprenoids may be produced by the cultivation of these actinomycete
      strains. During the course of these studies, we identified diterpene cyclases
      possessing unique primary structures that differ from those of eukaryotes and
      catalyze unique reactions.

PMID- 15981410
TI  - Aurafuron A and B, new bioactive polyketides from Stigmatella aurantiaca and
      Archangium gephyra (Myxobacteria). Fermentation, isolation, physico-chemical
      properties, structure and biological activity.
AB  - New antibiotic polyketides, named aurafuron A (1) and B (2) were isolated from
      culture extracts of myxobacteria of the species Stigmatella aurantiaca and
      Archangium gephyra, strain Ar 10844. By multi-step chromatography 1 and 2 were
      separated from a variety of other non-related co-metabolites, and their
      structures elucidated by spectroscopic methods as new 5-alkenyl-3 3(2H)
      furanones. Aurafurons inhibited the growth of some filamentous fungi and
      additionally, aurafuron B was weakly active against few Gram-positive bacteria.
      Both compounds also showed cytotoxic activity against the mouse fibroblast cell
      line L929.

PMID- 15981411
TI  - Phenatic acids A and B, new potentiators of antifungal miconazole activity
      produced by Streptomyces sp. K03-0132.
AB  - Two new phenols, designated phenatic acids A and B, were isolated along with
      known actiphenol, from the culture of Streptomyces sp. K03-0132 by solvent
      extraction, silica gel column chromatography and HPLC. Their structures were
      elucidated by spectroscopic analyses including mainly various NMR experiments.
      They have a common 1-hydroxy 2, 4-dimethyl benzene ring. These compounds
      potentiate miconazole activity against Candida albicans. Phenatic acid B also
      showed moderate antimicrobial activity against Bacillus subtilis, Staphylococcus
      aureus, Bacteroides fragilis and Acholeplasma laidlawii.

PMID- 15981412
TI  - Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. II. Structure
      elucidation.
AB  - During the screening program for new antibacterial agents produced by
      actinomycetes, GE23077 was isolated from fermentation broths of an Actinomadura
      sp. strain as a complex of factors A1, A2, B1, B2. NMR, MS and GC/MS analysis
      carried out on the isolated components led to the conclusion that GE23077 is a
      novel cyclic heptapeptide consisting of common and unusual amino acids. The
      chemical structures of the complex components were elucidated. Components A and B
      differ in the structure of the acyl group connected to a 2,3-diaminopropanoic
      acid moiety. A alpha-amino-malonic acid residue in the peptidic sequence is the
      origin of an isomerization process between A1 and A2 as well as B1 and B2. The
      chirality of the alpha-amino-malonic acid residue can be inverted easily via keto
      enol tautomerism. Factors A2 and B2 should be considered as epimers of A1 and B1
      respectively. By degradation studies the absolute configuration of some amino
      acids were determined. Chiral GC-MS and Micellar Electrokinetic Capillary
      Chromatography (MEKC) were used to define the absolute stereochemistries of five
      out of ten chiral centers.

PMID- 15981413
TI  - Xylactam, a new nitrogen-containing compound from the fruiting bodies of
      ascomycete Xylaria euglossa.
AB  - A novel nitrogen-containing compound, named xylactam (1), was isolated from the
      fruiting bodies of ascomycete Xylaria euglossa together with two known compounds
      penochalasin B2 and neoechinulin A. Their structures were elucidated on the basis
      of spectral data.

PMID- 15981414
TI  - Fumaquinone, a new prenylated naphthoquinone from Streptomyces fumanus.
AB  - A new prenylated naphthoquinone antibiotic, fumaquinone (5,7-dihydroxy-2-methoxy
      3-methyl-6-(3-methyl-but-2-enyl)[1,4]naphthoquinone) was isolated from cultures
      of Streptomyces fumanus (LL-F42248). Its chemical structure was determined
      primarily by NMR spectroscopy. Preliminary feeding experiments indicated the
      naphthoquinone is of polyketide origin, while the O-methyl and aromatic C-methyl
      groups are derived from methionine.

PMID- 15981415
TI  - Studies on terpenoids produced by actinomycetes. Isolation and structural
      elucidation of antioxidative agents, naphterpins B and C.
AB  - As a result of screening for terpenoids produced by Actinomycetes, naphterpins B
      and C, two new congeners of naphterpin were isolated from Streptomyces sp. CL190
      and their structures were determined by NMR spectral analysis.

PMID- 15981416
TI  - A novel aspochalasin with HIV-1 integrase inhibitory activity from Aspergillus
      flavipes.
AB  - A novel aspochalasin, aspochalasin L (1), was isolated from the fermentation
      broth of a soil-derived fungal culture identified as Aspergillus flavipes
      (Deuteromycota). Structure elucidation of 1 was accomplished by detailed
      spectroscopic data analyses and by comparison with related cytochalasins.
      Aspochalasin L demonstrated activity against HIV integrase with an IC50 of
      71.7microM.

PMID- 15981417
TI  - Spectinomycin resistance in rpsE mutants is recessive in Streptomyces
      roseosporus.
AB  - Eight spontaneous mutants of Streptomyces roseosporus resistant to spectinomycin
      (SpcR) were mapped to distinct transversions or deletions in the rpsE gene. Most
      of the mutations were strongly recessive to the wild type SpcS allele. This
      suggests that some SpcR alleles of rpsE may be useful in a spectinomycin based
      counter-selection system.

PMID- 15981418
TI  - Mechercharmycins A and B, cytotoxic substances from marine-derived
      Thermoactinomyces sp. YM3-251.
AB  - A new cytotoxic substance named mechercharmycin A was isolated from marine
      derived Thermoactinomyces sp. YM3-251. The structure of mechercharmycin A was
      determined by an X-ray crystallographic analysis to be cyclic peptide-like and
      bearing four oxazoles and a thiazole. Mechercharmycin B, a linear congener of
      mechercharmycin A, was also isolated from the same bacterium. Mechercharmycin A
      exhibited relatively strong antitumor activity, whereas mechercharmycin B
      exhibited almost no such activity.

PMID- 15981419
TI  - A novel active analogue of gramicidin S with smaller ring size.
AB  - A novel active gramicidin S analogue with smaller ring size, cyclo[-delta-Orn(
      Val-Pro-D-Phe-H)-Leu-]2, was synthesized and examined the structure-activity
      relationship. Its analogue showed antibiotic activity against all Gram-positive
      microorganisms tested, and its activity was 1/2-1/8 of that of gramicidin S. The
      present results indicated that both structures of cyclo(-delta-Orn-Leu-)2 and H-D
      Phe-Pro-Val sequence play the important role for showing the antibiotic activity.

PMID- 15981420
TI  - [Urinary lithiasis. Present and future].

PMID- 15981421
TI  - [Proceedings in the implantation of a laparoscopic radical prostatectomy
      program].
AB  - OBJECTIVE: To describe our proceedings in the implatation of our laparoscopic
      radical prostatectomy program (LRP). METHODS: Our working agenda and step
      oriented implementation of our LRP program are shown. RESULTS: Four main steps
      were scheduled to acomplish this goal. These were: Preparatory phase, programed
      open conversion, development and analysis. Overlapping of each of these phase
      occured although their major content run on a time-basis. After basic skills
      acquisition and updating of our equipment we moved into the fixed-time open
      conversion we allowed us to progresively improve our performance without putting
      our patients into risks. Operative time of this phase exceeds that of our open
      cases in 63 minutes and no major complications took place. A rapid decrease in
      the operative time was noted after the first 15 cases (197' vs 264'). CONCLUSION:
      Implantation of a program of LRP can be done safely with a pre-planned program
      tailored to the needs and characteristics of each group and institution.

PMID- 15981422
TI  - [Testicular and paratesticular prepuberal tumors: our experience and update on
      the topic].
AB  - OBJECTIVES: To evaluate the importance of testicular and paratesticular
      prepubertal tumors in our center and to make an update on the topic. METHODS AND
      PATIENTS: Data from all patients diagnosed of testicular and paratesticular
      prepubertal tumors and treated in our pediatric oncology unit from January 1st
      1998 to December 31st 2003 have been revised. RESULTS: Seven cases are reported
      among one hundred and ninety patients (represents 3,68 percent of all treated
      tumors): five tumors affecting the testis and two cases of paratesticular tumors.
      Pathology classification was as follows: one yolk sack tumor, one mature
      teratoma, two nongerminomatous testicular tumors (one Sertoli cell tumor and one
      unclassifiable), one Burkitt's lymphoma and two paratesticular rhabdomyosarcomas.
      Primary approach was inguinal radical orchiectomy in all cases except neoadjuvant
      chemotherapy in the case of lymphoma and partial escrotectomy in one patient
      previously managed with transcrotal orchiectomy. Rhabdomyosarcoma cases received
      adjuvant chemotherapy. All patients are alive and well after a follow-up period
      ranging from 17 to 74 months. CONCLUSIONS: Testicular and paratesticular
      prepubertal tumors are rare. Except for one patient affected of lymphoma,
      surgical primary approach have been essential for treatment. The prognoses in
      this series has been excellent.

PMID- 15981423
TI  - [Ileal neobladder with double chimney. Ureterointestinal anastomosis].
AB  - Radical cystoprostatectomy is accepted as the standard treatment for muscle
      invasive bladder cancer. During last years the indications for orthotopic
      neobladders have increased due to their advantages over other kind of diversions.
      Hautmann neobladder is one of the most commonly used. Several modifications have
      been later described. For example, after perform the W-shape pouch ureters can be
      anastomosed to a not-detubularized bowel segment (chimney modification). Here is
      described a modification of the Hautmann neobladder with two chimneys. Each
      ureter is spatulated in a golf club manner and anastomosed to the open end of
      each bowel loop. This kind of anastomosis provides several advantages. It is
      possible to use shorter ureteral segments by increasing the length of bowel used.
      It allows an anastomosis without tension, and less ischemia so the risk of
      stenosis and fistula is decreased. It is not necessary to perform additional
      enterothomies and in case of reintervention it is easier to access each
      anastomosis without damaging the other one.

PMID- 15981424
TI  - [Infection for papillomavirus in the man. Current state].
AB  - The Virus of the Human Papiloma (HPV), classically he/she has been related with
      infections of sexual transmission and processes wicked oncologists of the
      feminine genital apparatus and with less frequency of the masculine one. The new
      technical diagnostics, based on molecular biology (by means of polymerase chain
      reaction), they help to a better epidemic approach, an improvement in the I
      diagnose viral, and a correct therapeutic focus. The object of this work is to
      revise the current state of the HPV from the points of view etiopathogenics,
      epidemic, clinical, diagnosis, therapeutic and preservative.

PMID- 15981425
TI  - [A comparative study of the renal damage produced after the extracorporeal shock
      wave lithotripsy according to the lithiasis location].
AB  - INTRODUCTION: The Extracorporeal shock waves lithotripsy (ESWL) is fundamental in
      the treatment of lithiasis. However, there are evidences that it can produce
      renal damage. The objective of our study is to determine the degree of
      affectation of the glomerular and tubular function after ESWL, and the influence
      of the lithiasis location on the type of renal damage. MATERIAL AND METHODS: A
      prospective longitudinal study was carried out in 14 patients with normal renal
      function subjected to ESWL. We determined the basal level, and the levels at the
      24 hours, at the 4th and the 10th day post ESWL of: microalbuminuria (MA) (that
      values the glomerular function), and N-acetyl glucosamide (NAG) and alanine
      aminopeptidase (AAP), (that value the tubular function). RESULTS: The basal
      levels of of MA, NAG and AAP didn't show significant differences in connection
      with the localization of the stones. A significant increase was observed of the
      three parameters only 24 hours post ESWL. No significant differences were
      observed between the variation of the microalbuminuria levels, AAP and NAG and
      the treatment in relation to the localization of the stones. CONCLUSIONS: It
      exists a glomerular and tubular damage after ESWL. This damage is not related
      with the pelvic or calicial location of the stones. In patient with previous
      normal renal function, the renal damage recovers at the 4th day post ESWL.

PMID- 15981426
TI  - [Nocturia in female with symptoms of urinary incontinence: analysis of associated
      clinical and urodynamic variables].
AB  - BACKGROUND: There is little information about urodynamic characteristics of
      females with symptoms of urinary incontinence (UI) and nocturia. METHOD:
      Descriptive study of 1731 females consecutively referred with symptoms of UI for
      study and treatment. Urogynaecological history, physical examination and
      urodynamic study were carried out. Patients with pelvic organ prolapse greater
      than second degree were excluded. Frequency of nocturia symptom and its
      relationship with urodynamic, personal and clinical variables were analysed.
      RESULTS: 743 patients (43%) of those included presented nocturia. Urodynamic
      diagnoses in patients with nocturia were: stress UI in 262 patients (35.4%);
      detrusor overactivity in 166 (22.3%); and both in 220 (29.6%). The rest (12.7%)
      had other diagnoses. Mean (S.D.) bladder capacity of patients with nocturia was
      less than that of the rest of patients: 459.8 (159.8) vs 530.6 (216.9) ml
      (p<0.001). Of all the variables associated with nocturia, those which showed
      independent association were (ExpB; 95%CI): age >65 years (1.88; 1.34-2.63);
      menopause (2.11; 1.56-2.86); hypertension (1.42; 1.04-1.94) and bladder
      cistometric capacity less than 300 (1.71; 1.01-2.91) and between 300 and 400
      (1.67; 1.17-2.38). The urodynamic diagnosis of Stress UI was associated with the
      absence of nocturia. CONCLUSION: Nocturia is a frequent symptom among females
      complaining of urinary incontinence. Its presence is associated to age over 65
      years, menopause, hypertension and reduced bladder capacity.

PMID- 15981427
TI  - [Use of paroxetine on-demand in premature ejaculation].
AB  - INTRODUCTION: It has been described varied definitions of premature ejaculation
      (PE), which has determined different prevalences and rates of success for the
      different therapies with selective serotonin re-uptake inhibitors. Our goal was
      evaluate the effectiveness of paroxetine like treatment of premature ejaculation
      administered on-demand (4-6 hours previous to intercourse) compared to the scheme
      of daily dose. PATIENTS AND METHOD: A prospective study type crossover was
      designed with 14 patients. Grupo A: 7 patient received paroxetine 20 mg/d by
      three weeks followed by paroxetine 20 mg 4-6 hours before the intercourse by
      three weeks. Group B: the other 7 patients received the same scheme but replacing
      by placebo. Later to three weeks of therapy suspension, crossover was made.
      RESULTS: The intravaginal ejaculatory latency time (IELT) pre-treatment was 0.4
      minutes. In the group A the IELT average was of 4.3 minutes in the treatment with
      daily paroxetine; 5.8 minutes when they received paroxetine on-demanad; 0.9 with
      daily placebo and 0.6 with placebo on-demand (p < 0.001). For group B the IELT
      during the daily placebo was 0.8 minutes and with placebo on-demand it was of
      1.1. When they received daily paroxetine the IELT was 3.3 minutes and during the
      phase of paroxetine on-demand it was increased to 6.1 (p<0.001). CONCLUSIONS: The
      treatment of premature ejaculation with paroxetine in daily dose and scheme on
      demand appears similar like effective options.

PMID- 15981428
TI  - [Recent advances in the comprehension of the effects of cold ischemia in kidney
      graft].
AB  - Cold ischemia is the best known method to preserve kidneys for transplant.
      However, it produces several detrimental effects. First, cellular necrosis.
      Secondarily, during the hypothermic period a mitochondrial injury process
      develops which makes the cell entering a pre-apoptotic state. This apoptosis
      occurs definitively in the reperfusion. Preservation solutions currently
      available are not perfect and are not able to avoid cold-related cell injuries.
      The addition of certain substances to UW solution (desferrioxamine) has shown
      experimentally a reduction in mitochondrial cold-related lesions. Isolated
      hypothermic kidney perfusion reduces initial graft dysfunction about 20% in
      comparison to hypothermic storage. This fact relates to important either
      economical as functional consequences.

PMID- 15981429
TI  - [Bulbourethral sling. The experience of our service].
AB  - OBJECTIVES: The authors present the clinic results obtained with the
      bulbourethral sling application with pubic bone anchorage (Invance) in patients
      with stress urinary incontinence. MATERIAL AND METHODS: From July to December
      2003, 10 slings were implanted in men between the 60's and the 83 years old
      (average 72.6 years), whose incontinence appeared after prostatic surgery (retro
      pubic radical prostatectomy, perineal radical prostatectomy, radical
      cystoprostatectomy with Camey II neobladder, transurethral resection,
      transvesical prostate adenomectomy). RESULTS: After 9 months follow-up (3 to 7
      months), 8 patients (80%) are continent (without need of using any pad) and 2
      (20%) show minimum leakage with effort (need of 1 to 2 daily pads). All are
      satisfied with the surgery result. Two patients referred perineal pain, which was
      solved with Paracetamol. There was no case of perineal haematoma, infection,
      rejection or urethral erosion. CONCLUSION: The bulbourethral sling with bone
      anchorage is a rather invasive procedure, of easy technical execution, with high
      continence rates and associated to low morbidity. Although the presented results
      been an incentive to the technique prolongation, it would be necessary a higher
      tracking: and higher global experience in order that this sling affirm and
      transform itself in an alternative to the artificial sphincter in selected cases.

PMID- 15981430
TI  - [Micropapillary carcinoma of the bladder: case report and review of the
      literature].
AB  - Micropapillary carcinoma is an uncommon pathologic variant of bladder carcinoma
      with aggressive behavior. Its usual presentation is like a high grade and high
      stage carcinoma and associated with other histologic types in different
      proportion. It doesn't differ clinically from normal transitional cell carcinoma
      of the bladder. Studies of molecular markers are still contradictories. Treatment
      should be early and aggresive, based on surgical therapy as radiotherapy and
      chemotherapy have shown limited results. We report a 72 year old man suffering
      from low urinary tract symptoms for years and recently presented gross hematuria.
      He was diagnosed as high stage micropapillary carcinoma. One year after radical
      cystectomy and subsequent chemotherapy based on carboplatin and gemcitabine,
      progression of the disease was shown on CT and the patient died 14 months after
      the diagnosis.

PMID- 15981431
TI  - [Erythrocytosis related with hydronephrosis in a horseshoe kidney].
AB  - We report a case of a man with erythrocytosis secondary to hydronephrosis in a
      right horseshoe kidney. The patient had an advanced hydronephrosis because of
      ureteropelvic junction obstruction occupying the right hemiabdomen. Following
      nephrectomy of the right kidney erythrocyte count returned to normal values.
      Secondary polyglobulia may be due to increased erythropoietine values and has
      been related in some patients with renal diseases such as hydronephrosis, but
      very rarely in association with hydronephrotic horseshoe kidney.

PMID- 15981432
TI  - [Malignant retroperitoneal schwannoma].
AB  - We present an uncommon case of retroperitoneal malignant schwannoma diagnosed
      accidentally. The clinical, diagnostic and therapeutic features are discussed.

PMID- 15981433
TI  - [Primary lymphoepithelioma-like carcinoma urinary bladder].
AB  - OBJECTIVE: To present a new case of a primary lymphoepithelioma-like carcinoma of
      the urinary bladder. MATERIAL AND METHODS: We describe the clinical, diagnosis,
      treatment and development of this kind of tumor. Review of the literature.
      CONCLUSIONS: It is an unusual type of bladder cancer that requires a carefully
      analyse from the pathologist and a confirmation by means of immunohistochemistry
      techniques. The focal form is associated with poor prognosis. Radical cystectomy
      is the gold standard. This kind of tumor has sensibility to chemo and
      radiotherapy, who can be used as adjuvant therapy.

PMID- 15981434
TI  - [Inverted papilloma of the upper urinary tract].
AB  - Inverted papilloma of the upper urinary tract is a rare tumor and generally
      considered to be a benign. We present two cases of benign ureteral inverted
      papilloma. They were discovered after to study a upper urinary infection and a
      gross hematuria respectively. Both cases appear to be associated with
      asynchronous and synchronous bladder carcinoma, so it is very important a strict
      follow-up.

PMID- 15981435
TI  - [Non-Hodgkin's lymphoma and urinary tract. About a case reported].
AB  - We pass to describe a case of non Hodgkin's secondary lymphoma with metachronic
      affectation in bladder and left kidney, in a patient with different extranodals
      locations. Both in bladder and kidney, it was a low grade lymphoma type B with
      centrofolicular cells. We suggest haematogenous dissemination and affinity of
      lymphomatous clone to the urinary tract. We establish some diagnostic
      considerations, such about the therapeutic management in this type of
      pathologies.

PMID- 15981436
TI  - [Laparoscopy in retroperitoneal fibrosis].

PMID- 15981437
TI  - [Severe renal traumatism with conservative treatment].

PMID- 15981438
TI  - Academic medicine and health improvements in India.

PMID- 15981439
TI  - Cardiovascular risk factor prevalence among men in a large industry of northern
      India.
AB  - BACKGROUND: Industrial settings, with their intramural resources and healthcare
      infrastructure, are ideal for initiating preventive activities to increase the
      awareness and control of cardiovascular diseases (CVD). However, there are no
      reliable estimates of CVD and risk factor burden, nor of its awareness and
      treatment status in urban Indian industrial settings. We aimed to evaluate the
      prevalence of CVD and its risk factors, and to assess the status of awareness and
      control of CVD risk factors among a large industrial population of northern
      India. METHODS: We conducted a cross-sectional survey among all employees aged 20
      59 years of a large industry near Delhi (n=2935), to evaluate their
      cardiovascular risk profile--by employing a structured questionnaire and clinical
      and biochemical estimations. The presence of coronary heart disease was
      ascertained by evidence of its treatment, Rose angina questionnaire and Minnesota
      coded electrocardiograms. RESULTS: The results for 2122 men, in whom complete
      information was available, are reported here. The mean age was 42 years and 90%
      of the men were below 50 years of age. The prevalence of major CVD risk factors
      (95% CI) was: hypertension 30% (28%-32%), diabetes 15% (14%-17%), high serum
      total cholesterol/HDL ratio (> or = 4.5) 62% (60%-64%) and current smoking 36%
      (34%-38%). Forty-seven per cent of the respondents had at least two of these risk
      factors. Another 44% (95% CI: 42%-46%) had pre-hypertension (INC VII criteria)
      and 37% (95% CI: 35%-39%) had evidence of either impaired fasting glucose or
      impaired glucose tolerance. Thirty-five per cent (95% CI: 33%-37%) of the
      individuals were overweight (BMI > or = 25 kg/m2) while 43% (95% CI: 40%-45%) had
      central obesity (waist circumference >90 cm). The metabolic syndrome was present
      in 28%-35% of the individuals depending on the diagnostic criteria used. The
      prevalence of several risk factors and the metabolic syndrome was high with
      increasing age, BMI and waist circumference. A third of those who had
      hypertension (31.5%) and diabetes (31%) were aware of their status. Among those
      aware, adequate control of blood pressure and blood glucose was present in only
      38% of those with hypertension and 31% of those with diabetes, respectively.
      Coronary heart disease was present in 7.3% of the individuals while 0.3% had a
      history of stroke. CONCLUSION: This study demonstrates the high prevalence of CVD
      and its risk factors against a background of poor awareness and control among a
      comparatively young male population in a north Indian industrial setting.

PMID- 15981440
TI  - Safety and efficacy of an indigenous recombinant interferon-alpha-2b in patients
      with chronic myelogenous leukaemia: results of a multicentre trial from India.
AB  - BACKGROUND: Compared to hydroxyurea, treatment with interferon-alpha (IFN-alpha)
      is known to prolong survival in patients with chronic phase of chronic
      myelogenous leukaemia (CML) and was considered as first-line therapy till
      recently. We conducted a multicentre trial using an indigenous recombinant IFN
      alpha-2b to evaluate its efficacy and toxicity in chronic phase CML. METHODS:
      Between September 2000 and August 2001, patients with chronic phase CML were
      recruited within 8 weeks of diagnosis at 7 centres in India. The study was
      approved by the Ethics Committee of each participating Institute and Informed,
      written consent was obtained from all patients. All patients were given the study
      drug in a dose of 5 million units daily subcutaneously. Response and survival
      analyses were done with intent-to-treat analysis. RESULTS: One hundred and
      fourteen patients (75 men and 39 women) were included in the study. Their ages
      ranged from 18 to 62 years (median 37 years). Fifty-seven per cent of patients
      had a haematological response; complete response in 31.6% and partial response in
      25.4%. The median time to achieve complete haematological response was 6 months
      (range 3-12 months). Cytogenetic response was seen in 39.4% of patients; complete
      in 1.8%, partial in 28% and minimal in 9.6%. The median time to achieve partial
      and complete cytogenetic response was 6 and 12 months, respectively. Nineteen
      patients had progression (blast crisis n=15, accelerated phase n=4) while on
      treatment. Two patients refused further treatment after the initial 4 weeks due
      to IFN-a toxicity, mainly bone pains and fever. The major toxic effects of
      treatment were fever (78%), fatigue (25.4%) and myalgia (52%). No patient died of
      toxicity. Currently, 95 patients are alive, 91 in the chronic phase and 4 in the
      accelerated phase. Four patients were lost to follow up and all 15 patients with
      blast crisis died of progressive disease at a median Interval of 6.5 months
      (range 1-15 months). The Kaplan-Meier probability of survival at 36 months was
      76%. CONCLUSION: This study confirms the efficacy of the indigenous recombinant
      IFN-alpha-2b in chronic phase CML. The drug has a toxicity profile similar to
      that of other preparations.

PMID- 15981441
TI  - Management of snake-bite in rural Maharashtra: a 10-year experience.
AB  - BACKGROUND: A high incidence of snake-bite envenomation has been reported from
      Marathwada, Maharashtra. This study analysed the pattern of snake-bites and their
      management in a rural area of India over a 10-year period. METHODS: A total of
      633 patients with snake-bite admitted to the Rural Community Centre and Punde
      Hospital in Mukhed taluka, Nanded district (Marathwada) of Maharashtra, between
      1992 and 2001, were analysed retrospectively. The local and systemic
      manifestations of snake-bite, response to antisnake venom, atropine and
      neostigmine, the treatment of complications and the outcome were analysed.
      RESULTS: Of the 633 patients, 427 (67.5%) had been bitten by poisonous snakes and
      206 (32.5%) by non-poisonous snakes. The majority of snake-bites (68.9%) occurred
      between May and November. Those affected were mainly farmers (228 [36%]),
      students (191 [30.2%]) and housewives (175 [27.6%]). Of the 427 envenomed by
      poisonous snakes, 274 (64.2%) were by Echis carinatus (saw-scaled viper), 71
      (16.6%) by cobra, 42 (9.8%) by krait and 40 (9.4%) by Russell viper. The
      requirement of antisnake venom for treating neurotoxic envenomation was 40-320 ml
      and for Echiscarinatus and Russell viper bites it was 20-250 ml. Among those
      envenomed by poisonous snakes, the mortality was 4.7% (n=20). CONCLUSION: Snake
      bite is a common life-threatening emergency in the study area. We observed an
      occupational risk and a seasonal incidence of snake-bite. Knowledge of the varied
      clinical manifestations of snake-bite are important for effective management.
      Ready availability and appropriate use of antisnake venom, close monitoring of
      patients, institution of ventilatory support and early referral to a larger
      hospital when required help in reducing the mortality. Most patients with snake
      bites can be successfully managed even in small rural hospitals with limited
      facilities.

PMID- 15981442
TI  - Massive gastrointestinal bleeding in a patient with AIDS.
AB  - Cytomegalovirus enteritis can lead to gastrointestinal bleeding in patients with
      the acquired immune deficiency syndrome. The commonest site of involvement is the
      colon, followed by the stomach and terminal ileum. Most of these lesions can be
      diagnosed by colonoscopy or gastroscopy. We present our experience of a patient
      with cytomegalovirus infection involving only the proximal jejunum causing
      massive lower gastrointestinal bleeding. Conventional endoscopy and imaging had
      failed to locate the source of bleeding. Enteroscopy performed at the time of
      laparotomy showed an ulcerated lesion in the jejunum. Resection followed by
      histological examination of the resected area confirmed the diagnosis of
      cytomegalovirus infection. In addition to highly active antiretroviral therapy,
      ganciclovir was given for 14 days in a dose of 5 mg/kg twice a day and tapered
      over a period of 3 months. There has been no further episode of gastrointestinal
      bleeding over a follow up of 9 months.

PMID- 15981443
TI  - von Willebrand disease: a laboratory approach.
AB  - von Willebrand disease (VWD) is a common inherited bleeding disorder. Accurate
      diagnosis and classification of VWD is crucial for clinical management. A
      detailed clinical history, including that of bleeding, is required. A family and
      drug history are also important. Genetic factors such as blood group, and
      environmental factors such as stress, trauma, pregnancy and inflammation should
      also be considered. The age, ethnic group and hormonal status could also affect
      the von Willebrand factor (VWF) levels. No single test is robust enough to detect
      all variants of VWD. In view of the heterogeneity of the disease and limitations
      in assays, a battery of tests should be performed before a final diagnosis can be
      reached. These include the screening coagulation tests, factor VIII:C assay, VWF
      antigen assay, assessment of functional VWF which includes VWF ristocetin
      cofactor assays, VWF collagen binding assay, ristocetin-induced platelet
      aggregation and VWF multimer analysis. The newer ELISA techniques based on VWF
      binding with factor VIII glycoprotein (Gp) 1b and cerebrosides have also helped
      in determining certain unusual forms of VWD. The advent of new systems such as
      platelet function analysers (PFA), thromboelastography (TEG) and clot signature
      analysers (CSA), which are designed to assess either the primary platelet
      function or as a global haemostasis screen, have facilitated and simplified the
      diagnosis. However, few centres all over the world can perform all these
      expensive tests to provide a final diagnosis of VWD. We reviewed the laboratory
      investigations required for a diagnosis of VWD. Apart from congenital VWD, the
      possibility of acquired VWD should be considered in those with a negative past
      history of bleeding or in the presence of an underlying disease.

PMID- 15981444
TI  - Proton magnetic resonance (1H MR) spectroscopy in common dementias.

PMID- 15981445
TI  - Renin-angiotensin-aldosterone system antagonists: preventing diabetic
      nephropathy.

PMID- 15981446
TI  - Concurrent alcohol and tobacco use among a middle-aged and elderly population in
      Mumbai.
AB  - BACKGROUND: The concurrent use of alcohol and tobacco and its deleterious effects
      have been reported in the western literature. However, studies on the
      relationship between concurrent alcohol and tobacco use in India are limited.
      This study outlines the association between concurrent alcohol and tobacco use
      among a middle-aged and elderly population in a western Indian cohort after
      controlling for various sociodemographic factors. METHODS: A total of 35 102 men,
      45 years of age and above were interviewed for concurrent alcohol and tobacco
      use. The sample was part of an earlier cohort drawn from the general population.
      The data were analysed after controlling for age, education, religion and mother
      tongue. RESULTS: Among alcohol users, 51.1% smoked tobacco and 35.6% used
      smokeless tobacco. The relative risk of alcohol use was highest among those
      smoking cigarettes or beedis and among those using mishri with betel quid and
      tobacco. The risk of alcohol use increased with the frequency of tobacco use. The
      risk also increased with higher amounts of alcohol consumption, but peaked at
      around 100-150 ml of absolute alcohol use. CONCLUSION: The study highlights the
      association between concurrent alcohol and tobacco use among the Indian
      population. This has important public health implications since concurrent use of
      these is synergistic for increased risk of oropharyngeal cancers.

PMID- 15981447
TI  - Introducing problem-based learning in physiology in the conventional Indian
      medical curriculum.
AB  - BACKGROUND: Problem-based learning (PBL) is a widely acclaimed student-centred
      learning method. However, there are few reports of its use in the traditional
      lecture-practical-tutorial model of learning. We used PBL for teaching one module
      of Physiology to first-year medical undergraduate students who had no prior
      exposure to PBL. METHODS: One hundred first-year medical undergraduates enrolled
      in a medical college, which follows the traditional teaching-learning methods,
      participated in the exercise. The scheduled classes on 'Physiology of the thyroid
      gland' were converted into a PBL block to be covered over a week. An orientation
      of the teachers and students to PBL was done, clinical cases selected and tutor
      guides prepared before the actual PBL week. During the PBL week, students were
      exposed to small group discussions and Interactive resource sessions, and were
      given time for self-study. The PBL week concluded with a review session and
      evaluation of the PBL block using questionnaires. RESULTS: A comparison of the
      pre- and post-PBL questionnaire showed a clear preference for PBL over the
      conventional curriculum for the interactive resource sessions and group
      discussions. Both students and teachers found PBL rewarding. CONCLUSION:
      Implementation of PBL is feasible even in a traditional set-up despite limited
      resources, rigid time schedules and little interaction among various disciplines.
      We hope our experience would encourage other teachers to introduce appropriately
      modified PBL in their ongoing curriculum.

PMID- 15981448
TI  - Reducing vascular disease risk: the undesirable and desirable guidelines.

PMID- 15981449
TI  - Toxicology: an ignored specialty?

PMID- 15981450
TI  - Letter from North America. Gene therapy in 2005.

PMID- 15981451
TI  - Letter from Mumbai.

PMID- 15981452
TI  - The last, but not the least, yet lost, author.

PMID- 15981453
TI  - The fallacy of assessment of Indian vegetarianism.

PMID- 15981454
TI  - Ethical issues in live operative workshops.

PMID- 15981455
TI  - Use of paracetamol as an analgesic in India.

PMID- 15981456
TI  - Bacterial virulence strategies that utilize Rho GTPases.
AB  - The ability to modify central host cellular functions is a major advantage to
      many bacterial pathogens that use such strategies as part of their virulence
      mechanisms. Small GTPases, including Rho GTPases, make particularly attractive
      targets for pathogens because of their central roles in modulating cellular
      functions such as cytoskeletal control. Such modifications of these GTPases can
      include direct chemical modification of the GTPase or interfacing with some of
      the regulatory elements associated with GTPase control. Pathogens use these
      alterations in GTPase functions for a variety of functions, including killing the
      host cell, mediating bacterial uptake into the host cell (invasion),
      reprogramming actin to form a lesion in host cells underlying adherent bacteria,
      to mediate intracellular survival by affecting intracellular trafficking, or to
      provide polymerized actin mechanisms to propel microbes around inside host cells
      and into adjacent cells. Collectively, these examples represent many key
      microbial virulence mechanisms that have led to a much deeper understanding of
      both microbial pathogens and GTPase functions.

PMID- 15981457
TI  - Extracellular bacterial pathogens and small GTPases of the Rho family: an
      unexpected combination.
AB  - Even in the case of extracellular bacterial pathogens, it is becoming
      increasingly clear that successful colonization does not limit itself to passive
      attachment on the surface of human cells; a dialogue takes place between bacteria
      and infected cells. These pathogens modulate cellular functions to their
      advantage, leading to survival and proliferation at the cell surface.
      Furthermore, there is increasing evidence that a variety of extracellular
      pathogens activate small GTPases of the Rho family during adhesion, placing these
      regulators at the center of the interaction between these bacteria and their
      infected host.

PMID- 15981458
TI  - Triggered phagocytosis by Salmonella: bacterial molecular mimicry of RhoGTPase
      activation/deactivation.
AB  - Salmonella Typhimurium uses the type III secretion system encoded in the
      Salmonella pathogenicity island I (SPI-1 TTSS) to inject toxins (effector
      proteins) into host cells. Here, we focus on the functional mechanism of three of
      these toxins: SopE, SopE2, and SptP. All three effector proteins change the
      GTP/GDP loading state of RhoGTPases by transient interactions. SopE and SopE2
      mimic eukaryotic G-nucleotide exchange factors and thereby activate RhoGTPase
      signaling pathways in infected host cells. In contrast, a domain of SptP
      inactivates RhoGTPases by mimicking the activity of eukaryotic GTPase-activating
      proteins. The Salmonella-host cell interaction provides an excellent example for
      the use of molecular mimicry by bacterial pathogens.

PMID- 15981459
TI  - Regulation of phagocytosis by Rho GTPases.
AB  - Phagocytosis is the mechanism of internalization used by specialized cells such
      as macrophages, dendritic cells, and neutrophils to internalize, degrade, and
      eventually present peptides derived from particulate antigens. The phagocytic
      process comprises several sequential and complex events initiated by the
      recognition ofligands on the surface of the particles by specific receptors on
      the surface of the phagocytic cells. Receptor clustering at the attachment site
      generates a phagocytic signal that in turn leads to local polymerization of actin
      filaments and to particle internalization. Depending on the particles and
      receptors involved, it appears that the structures and mechanisms associated with
      particle ingestion are diverse. However, work during the past few years has
      highlighted the importance of small GTP-binding proteins of the Rho family in
      various types of phagocytosis. As reviewed here, Rho family GTPases, their
      activators, and their downstream effectors control the local reorganization of
      the actin cytoskeleton beneath bound particles.

PMID- 15981460
TI  - The immunological synapse and Rho GTPases.
AB  - Rho GTPases are molecular switches controlling a broad range of cellular
      processes including lymphocyte activation. Not surprisingly, Rho GTPases are now
      recognized as pivotal regulators of antigen-specific T cell activation by APCs
      and immunological synapse formation. This review summarizes recent advances in
      our understanding of how Rho GTPase-dependent pathways control T lymphocyte
      motility, polarization and activation.

PMID- 15981461
TI  - Rho GTPases and the control of the oxidative burst in polymorphonuclear
      leukocytes.
AB  - Stimulation of quiescent leukocytes activates the NADPH oxidase, a membrane
      associated enzyme system that generates superoxide and other reactive oxygen
      species (ROS) that are used to kill bacteria within the phagosome. This chapter
      describes this multicomponent NADPH oxidase system, one of the first cellular
      systems shown to be directly regulated by Rac GTPases. We present current models
      of NADPH oxidase regulation by Rac2 and describe how Rac2 activation controls the
      timing of ROS production in adherent neutrophils. The antagonistic role that
      Cdc42 plays as a competitor of Rac2 for binding to the cytochrome component of
      the NADPH oxidase is discussed as a possible mechanism for tonic regulation of
      ROS production during the formation of the phagosome. Finally, we briefly depict
      mechanisms by which invasive bacteria can alter (inhibit) NADPH oxidase function,
      focusing on the effects of invasive bacteria on components and assembly of the
      NADPH oxidase.

PMID- 15981462
TI  - Clostridial Rho-inhibiting protein toxins.
AB  - Rho proteins are master regulators of a large array of cellular functions,
      including control of cell morphology, cell migration and polarity,
      transcriptional activation, and cell cycle progression. They are the eukaryotic
      targets of various bacterial protein toxins and effectors, which activate or
      inactivate the GTPases. Here Rho-inactivating toxins and effectors are reviewed,
      including the families of large clostridial cytotoxins and C3-like transferases,
      which inactivate Rho GTPases by glucosylation and ADP-ribosylation, respectively.

PMID- 15981463
TI  - Modulation of Rho GTPases and the actin cytoskeleton by YopT of Yersinia.
AB  - Pathogenic Yersinia species evade the innate cellular immune response by
      injecting antihost effector proteins (Yersinia outer proteins, Yops) into host
      cells through a type III secretion (TTS) apparatus. One of the six effector Yops,
      YopT, inactivates the small GTPase RhoA by removing the geranylgeranylated C
      terminal cysteine. This cleavage results in release of RhoA from the cell
      membrane and subsequently in blockage of stress fiber formation. Thus YopT
      impairs cellular functions associated with cytoskeleton rearrangements.

PMID- 15981464
TI  - Bacterial toxins activating Rho GTPases.
AB  - The CNF1 toxin is produced by some uropathogenic (UPECs) andmeningitis-causing
      Escherichia coli strains. It belongs to a large family of bacterial virulence
      factors and toxins modifying cellular regulators of the actin cytoskeleton,
      namely the Rho GTPases. CNF1 autonomously enters the host cell cytosol, where it
      catalyzes the constitutive activation of Rho GTPases by deamidation. This
      activation is, however, attenuated because of activated Rho protein ubiquitin
      mediated proteasomal degradation. Both Rho protein activation and deactivation
      confer phagocytic properties on epithelial and endothelial cells, as well as
      epithelial cell motility and cell-cell junction dynamics. Transcriptome analysis
      using DNA microarray revealed that endothelial cells respond to high doses of
      CNF1 by launching a genetic program of host alarm. This host cell reaction to
      CNF1 intoxication also indicates that degradation of activated Rho proteins by
      the proteasome may lead to a lowering of the threshold of the intoxicated cell
      inflammatory response. These results are consistent with growing evidence that
      Rho proteins control the cell inflammatory responses. It is tempting to assume
      that Rho deregulation may participate in various immunological disorders also
      involved in cancer.

PMID- 15981465
TI  - Genetic comparison of the rhabdoviruses from animals and plants.
AB  - There are more than 160 viral species in the Rhabdovidae family, most of which
      can be grouped into one of the six genera including Vesiculovirus, Lyssavirus,
      Ephemerovirus, Novirhabdovirus, Cytorhabdovirus, and Nucleorhabdovirus. These
      viruses are not only morphologically similar but also genetically related.
      Analysis of viral genes shows that rhabdoviruses are more closely related to each
      other than to viruses in other families. With the development of reverse
      genetics, the functions of many cis- and trans-elements important in the process
      of viral transcription and replication have been clearly defined such as the
      leader, trailer, and the intergenic sequences. Furthermore, it has been shown
      that there are two entry sites for the RNA-dependent RNA polymerase: 3' entry for
      leader synthesis and RNA replication, and direct entry at the N gene start
      sequence for transcription of the monocistronic mRNAs.

PMID- 15981466
TI  - Australian bat lyssavirus: a recently discovered new rhabdovirus.
AB  - Australian bat lyssavirus (ABLV), first identified in 1996, has been associated
      with two human fatalities. ABLV is genetically and serologically distinct from,
      but is closely related to, classical rabies. It has a bullet-shaped morphology by
      electron microscopy. There are two strains of ABLV known: one circulates in
      frugivorous bats, sub-order Megachiroptera, and the other circulates in the
      smaller, mainly insectivorous bats, sub-order Microchiroptera. Each strain has
      been associated with one human fatality. Surveillance indicates infected bats are
      widespread at a low frequency on the Australian mainland. It is unclear how long
      ABLV has been present in Australia, although molecular clock studies suggest the
      two strains separated 950 or 1,700 years ago based on synonymous or non
      synonymous nucleotide changes, respectively. Recent serological surveys suggest a
      closely related virus may exist in the Philippines. Due to demonstrated cross
      protection in mice, rabies vaccine is used to prevent infection. Rabies post
      exposure prophylaxis (PEP) protocols have been adopted for when a human is
      scratched or bitten by a suspect bat. A long-term commitment to public health
      programs that test bats that have been involved in scratch or bite incidents,
      followed by PEP if appropriate, will be necessary to minimise further human
      infection.

PMID- 15981467
TI  - Pathogenesis of rabies.
AB  - Rabies is a central nervous system (CNS) disease that is almost invariably fatal.
      The causative agent is rabies virus (RV), a negative-stranded RNA virus of the
      rhabdovirus family. RV pathogenesis, like that of other viruses, is a multigenic
      trait. Recent findings indicate that in addition to the RV G protein viral
      elements that regulate gene expression, especially expression of the L gene, are
      also likely to play a role in RV pathogenesis. In vivo, RV infects almost
      exclusively neurons, and neuroinvasiveness is the major defining characteristic
      of a classical RV infection. A key factor in the neuroinvasion of RV is
      transsynaptic neuronal spread. While the ability of RV to spread from the post
      synaptic site to the pre-synaptic site is mediated by the RV G protein, the RV P
      protein might be an important determinant of retrograde transport of the virus
      within axons. Although the mechanism(s) by which an RV infection cause(s) a
      lethal neurological disease are still not well understood, the most significant
      factor underlying the lethal outcome of an RV infection appears to be the
      neuronal dysfunction due to drastically inhibited synthesis of proteins required
      in maintaining neuronal functions.

PMID- 15981468
TI  - Bovine ephemeral fever in Australia and the world.
AB  - Bovine ephemeral fever (BEF) is a disabling viral disease of cattle and water
      buffaloes. It can cause significant economic impact through reduced milk
      production in dairy herds, loss of condition in beef cattle and loss of draught
      animals at the time of harvest. Available evidence indicates clinical signs of
      BEF, which include bi-phasic fever, anorexia, muscle stiffness, ocular and nasal
      discharge, ruminal stasis and recumbency, are due primarily to a vascular
      inflammatory response. In Australia, between 1936 and 1976, BEF occurred in
      sweeping epizootics that commenced in the tropical far north and spread over vast
      cattle grazing areas of the continent. In the late 1970s, following several
      epizootics in rapid succession, the disease became enzootic in most of northern
      and eastern Australia. In Africa, the Middle East and Asia, BEF occurs as also
      epizootics which originate in enzootic tropical areas and sweep north or south to
      sub-tropical and temperate zones. The causative virus is transmitted by
      haematophagous insects that appear to be borne on the wind, allowing rapid spread
      of the disease. Bovine ephemeral fever virus (BEFV) has been classified as the
      type species of the genus Ephemerovirus in the Rhabdoviridae. It has a complex
      genome organization which includes two glycoprotein genes that appear to have
      arisen by gene duplication. The virion surface glycoprotein (G protein) contains
      four major antigenic sites that are targets for neutralizing antibody. An
      analysis of a large number of BEFV isolates collected in Australia between 1956
      and 1992 has indicated remarkable stability in most neutralization sites.
      However, epitope shifts have occurred in the major conformational site G3 and
      these have been traced to specific mutations in the amino acid sequence. BEFV
      isolates from mainland China and Taiwan are closely related to Australian
      isolates, but some variations have been detected. Natural BEFV infection induces
      a strong neutralizing antibody response and infection usually induces durable
      immunity. Several forms of live-attenuated, inactivated and recombinant vaccines
      have been reported but with variable efficacy and durability of protection. The
      BEFV G protein is a highly effective vaccine antigen, either as a purified
      subunit or expressed from recombinant viral vectors.

PMID- 15981469
TI  - Fish rhabdoviruses: molecular epidemiology and evolution.
AB  - Rhabdoviruses may cause serious diseases in wild and farmed fish. Within the
      Rhabdoviridae six genera have been established: Ephemerovirus, Cytorhabdovirus,
      Nucleorhabdovirus, Lyssavirus, Vesiculovirus, and Novirhabdovirus. Viruses that
      infect fish are official or tentative members of the genera Vesiculovirus and
      Novirhabdovirus, or are listed as unassigned rhabdoviruses. In this report, we
      summarize and discuss published and our own unpublished data on the molecular
      epidemiology and phylogeography of fish rhabdoviruses including intrapopulational
      differences and subgrouping of fish rhabdoviruses, in particular the species
      spring viremia of carp virus (SVCV), infectious hematopoietic necrosis virus
      (IHNV) and viral hemorrhagic septicemia virus (VHSV).

PMID- 15981470
TI  - Reverse genetics on fish rhabdoviruses: tools to study the pathogenesis of fish
      rhabdoviruses.
AB  - Rhabdoviruses, mainly in rainbow trout, are among the most devastating viruses
      for worldwide aquaculture. To date no effective treatments to fight against these
      viruses are available. During the past years, several approaches to develop
      efficient vaccines have been undertaken such as the use of immunogenic
      recombinant viral proteins, naked DNA or inactivated viruses. However, although
      these vaccines have been proven to be very effective on a small scale, they have
      never been used in the field because the vaccines would have to be injected into
      thousands of yearling trouts. The only alternative to injection consists of the
      development of attenuated live vaccines that can be administrated to trouts by
      bath immersion. Reverse genetics on trout rhabdoviruses offer the possibility of
      recovering a series of live recombinant viruses in which the viral genome has
      been irreversibly modified to generate cost-effective live, safe vaccines.

PMID- 15981471
TI  - Plant rhabdoviruses.
AB  - This chapter provides an overview of plant rhabdovirus structure and taxonomy,
      genome structure, protein function, and insect and plant infection. It is focused
      on recent research and unique aspects of rhabdovirus biology. Plant rhabdoviruses
      are transmitted by aphid, leafhopper or planthopper vectors, and the viruses
      replicate in both their insect and plant hosts. The two plant rhabdovirus genera,
      Nucleorhabdovirus and Cytorhabdovirus, can be distinguished on the basis of their
      intracellular site of morphogenesis in plant cells. All plant rhabdoviruses carry
      analogs of the five core genes: the nucleocapsid (N), phosphoprotein (P), matrix
      (M), glycoprotein (G) and large or polymerase (L). However, compared to
      vesiculoviruses that are composed of the five core genes, all plant rhabdoviruses
      encode more than these five genes, at least one of which is inserted between the
      P and M genes in the rhabdoviral genome. Interestingly, while these extra genes
      are not similar among plant rhabdoviruses, two encode proteins with similarity to
      the 30K superfamily of plant virus movement proteins. Analysis of
      nucleorhabdoviral protein sequences revealed nuclear localization signals for the
      N, P, M and L proteins, consistent with virus replication and morphogenesis of
      these viruses in the nucleus. Plant and insect factors that limit virus infection
      and transmission are discussed.

PMID- 15981472
TI  - Recombinant rhabdoviruses: vectors for vaccine development and gene therapy.
AB  - The establishment of methods to recover rhabdoviruses from cDNA, so-called
      reverse genetics systems, has made it possible to genetically engineer
      rhabdoviruses and to study all aspects of the virus life cycle by introducing
      defined mutations into the viral genomes. It has also opened the way to make use
      of the viruses in biomedical applications such as vaccination, gene therapy, or
      oncolytic virotherapy. The typical gene expression mode of rhabdoviruses, a high
      genetic stability, and the propensity to tolerate changes in the virus envelope
      have made rhabdoviruses attractive, targetable gene expression vectors. This
      chapter provides an overview on the possibilities to manipulate biological
      properties of the rhabdoviruses that may be important for further development of
      vaccine vectors and examples of recombinant rhabdoviruses expressing foreign
      genes and antigens.

PMID- 15981473
TI  - Selection of CD4+CD25+ regulatory T cells by self-peptides.
AB  - Regulatory T cells have been shown to prevent the development of autoimmune
      disease, and can modulate immune responses during infections or following tissue
      transplantation. Recently, the processes by which CD4+CD25+ regulatory T cells
      are produced during immune repertoire formation have begun to be elucidated. This
      review focuses on the role of self-peptides in mediating CD4+CD25+ regulatory T
      cell selection in the thymus. How self-peptides continue to have an important
      influence on the accumulation of CD4+CD25+ regulatory T cells in the periphery is
      also discussed.

PMID- 15981474
TI  - The role of TCR specificity in naturally arising CD25+ CD4+ regulatory T cell
      biology.
AB  - CD25+ CD4+ T cells (TR) are a naturally arising subset of regulatory T cells
      important for the preservation of self-tolerance and the prevention of
      autoimmunity. Although there is substantial data that TCR specificity is
      important for TR development and function, relatively little is known about the
      antigen specificity of naturally arising TR. Here, we will review the available
      evidence regarding naturally arising TR TCR specificity in the context of TR
      development, function, and homeostasis.

PMID- 15981475
TI  - Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection
      that isolates repertoires undergoing positive or negative selection.
AB  - The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al.
      1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that
      peripheral tissue-specific tolerance is centrally established in the thymus, by
      epithelial stromal cells (TEC). Subsequent experiments have shown that TEC
      tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are
      generated intrathymically by recognition of antigens expressed on TECs
      (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other
      observations, in 1996 Modigliani and colleagues derived a general model for the
      establishment and maintenance of natural tolerance (MM96) (Modigliani et al.
      1996b), with two central propositions: (1) T cell receptor (TCR)-dependent
      sorting of emergent repertoires generates TEC-specific Treg displaying the
      highest TCR self-affinities below deletion thresholds, thus isolating repertoires
      undergoing positive and negative selection; (2) Treg are intrathymically
      committed (and activated) for a unique differentiative pathway with regulatory
      effector functions. The model explained the embryonic/perinatal time window of
      natural tolerance acquisition, by developmental programs determining (1) TCR
      multireactivity, (2) the cellular composition in the thymic stroma (relative
      abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral
      lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that
      remain recruitable to regulatory functions. We discuss here the MM96 in the light
      of recent results demonstrating the promiscuous expression of tissue-specific
      antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter
      et al. 2004) and indicating that Treg represent a unique differentiative pathway
      (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted
      by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan
      et al. 2001; Apostolou et al. 2002). In the likelihood that autoimmune diseases
      (AID) result from Treg deficits, some of which might have a thymic origin, we
      also speculate on therapeutic strategies aiming at selectively stimulating their
      de novo production or peripheral function, within recent findings on Treg
      responses to inflammation (Caramalho et al. 2003; Lopes-Carvalho et al.,
      submitted, Caramalho et al., submitted). In short, the MM96 argued that natural
      tolerance is dominant, established and maintained by the activity of Treg, which
      are selected upon high-affinity recognition of self-ligands on TECs, and
      committed intrathymically to a unique differentiative pathway geared to anti
      inflammatory and antiproliferative effector functions. By postulating the
      intrathymic deletion of self-reactivities on hemopoietic stromal cells (THC),
      together with the inability of peripheral resident lymphocytes to engage in the
      regulatory pathway, the MM96 simultaneously explained the maintenance of
      responsiveness to non-self in a context of suppression mediating dominant self
      tolerance. The major difficulty of the MM96 is related to the apparent tissue
      specificity of Treg repertoires generated intrathymically. This difficulty has
      now been principally solved by the work of Hanahan, Kyewski and others (Jolicoeur
      et al. 1994; Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004),
      demonstrating the selective expression of a variety of tissue-specific antigens
      by TECs, in topological patterns that are compatible with the MM96, but difficult
      to conciliate with recessive tolerance models (Kappler et al. 1987; Kisielow et
      al. 1988). While the developmentally regulated multireactivity of TCR repertoires
      (Gavin and Bevan 1995), as well as the peripheral recruitment of Treg among RTE
      (Modigliani et al. 1996a) might add to this process, it would seem that the
      establishment of tissue-specific tolerance essentially stems from the
      "promiscuous expression of tissue antigens" by TEC. The findings of AID resulting
      from natural mutations (reviewed in Pitkanen and Peterson 2003) or the targeted
      inactivation (Anderson et al. 2002; Ramsey et al. 2002) of the AIRE transcription
      factor that regulates promiscuous gene expression on TECs support this
      conclusion. The observations on the correlation of natural or forced expression
      of the Foxp3 transcription factor in CD4 T cells with Treg phenotype and function
      (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003) provided support
      for the MM96 contention that Treg represent a unique differentiative pathway that
      is naturally established inside the thymus. Furthermore, Caton and colleagues
      (Jordan et al. 2001), as well as several other groups (Bensinger et al. 2001;
      Apostolou et al. 2002), have provided direct evidence for our postulate that Treg
      are selected among differentiating CD4 T cells with high affinity for ligands
      expressed on TECs (Modigliani et al. 1996b). Finally, the demonstration by
      Caramalho et al. that Treg express innate immunity receptors (Caramalho et al.
      2003) and respond to pro-inflammatory signals and products of inflammation
      (Caramalho et al., submitted) brought about a new understanding on the peripheral
      regulation of Treg function. Together with the observation that Treg also respond
      to ongoing activities of "naive/effector" T cells--possibly through the IL-2
      produced in these conditions--these findings explain the participation of Treg in
      all immune responses (Onizuka et al. 1999; Shimizu et al. 1999; Annacker et al.
      2001; Curotto de Lafaille et al. 2001; Almeida et al. 2002; Shevach 2002; Bach
      and Francois Bach 2003; Wood and Sakaguchi 2003; Mittrucker and Kaufmann 2004;
      Sakaguchi 2004), beyond their fundamental role in ensuring self-tolerance (e.g.,
      Modigliani et al. 1996a; Shevach 2000; Hori et al. 2003; Sakaguchi 2004; Thompson
      and Powrie 2004). Thus, anti-inflammatory and anti-proliferative Treg are
      amplified by signals that promote or mediate inflammation and proliferation,
      accounting for the quality control of responses (Coutinho et al. 2001). In turn,
      such natural regulation of Treg by immune responses to non-self may well explain
      the alarming epidemiology of allergic and AID in wealthy societies (Wills-Karp et
      al. 2001; Bach 2002; Yazdanbakhsh et al. 2002), where a variety of childhood
      infections have become rare or absent. Thus, it is plausible that Treg were
      evolutionarily set by a given density of infectious agents in the environment.
      With hindsight, it is not too surprising that natural Treg performance falls once
      hygiene, vaccination, and antibiotics suddenly (i.e., 100 years) plunged
      infectious density to below some critical physiological threshold. As the immune
      system is not adapted to modern clean conditions of postnatal development,
      clinical immunologists must now deal with frequent Treg deficiencies (allergies
      and AID) for which they have no curative or rational treatments. It is essential,
      therefore, that basic immunologists concentrate on strategies to selectively
      stimulate the production, survival, and activity of this set of lymphocytes that
      is instrumental in preventing immune pathology. We have argued that the culprit
      of this inability of basic research to solve major clinical problems has been the
      self-righteousness of recessive tolerance champions, from Ehrlich to some of our
      contemporaries. It is ironical, however, that none of us--including the heretic
      opponents of horror autotoxicus--had understood that self-tolerance, or its
      robustness at least, is in part determined by the frequency and intensity of the
      responses to non-self. In the evolution of ideas on immunological tolerance, the
      time might be ripe for some kinds of synthesis. First, conventional theory
      reduced self-tolerance to negative selection and microbial defense to positive
      selection, while the MM96 solution was the precise opposite: positive selection
      of autoreactivities for self-tolerance (Treg) and negative selection (of Treg)
      for ridding responses. In contrast, it would now appear that positive and
      negative selection of autoreactive T cells are both necessary to establish either
      self-tolerance or competence to eliminate microbes, two processes that actually
      reinforce each other in the maintenance of self-integrity. Second, V-region
      recognition has generally been held responsible for specific discrimination
      between what should be either tolerated or eliminated from the organism. In
      contrast again, it would now seem that both processes of self-tolerance and
      microbial defense (self/non-self discrimination) also operate on the basis of
      evolutionarily ancient, germ-line-encoded innate, nonspecific receptors
      (Medzhitov and Janeway 2000) capable of a coarse level of self/non-self
      discrimination (Coutinho 1975). It could thus be interesting to revisit notions
      of cooperativity between V-regions and such mitogen receptors, both in single
      cell functions (Coutinho et al. 1974) and in the system's evolution (Coutinho
      1975, 1980) as well. After all, major transitions in evolution were cooperative
      (Maynard-Smith and Szathmary 1995).

PMID- 15981476
TI  - Selection and behavior of CD4+ CD25+ T cells in vivo: lessons from T cell
      receptor transgenic models.
AB  - Despite great interest in CD4+ CD25+ suppressor T cells, many of the fundamental
      properties of these cells remain enigmatic. This is in part due to experimental
      limitations inherent to the study of polyclonal suppressor T cells, and the
      extensive use of in vitro assays. This review article intends to outline recent
      advances in our understanding of the biology of suppressor T cells that have
      emerged from the analysis of T cell receptor (TCR) transgenic models. Several
      laboratories have taken advantage of model systems in which suppressor T cells of
      defined antigen-specificity are naturally selected in order to characterize the
      selection and behavior of these cells in vivo. In addition to providing valuable
      insights into the mechanism of differentiation of suppressor T cells, these
      systems now offer new possibilities for understanding the mode of action of
      suppressor T cells. For example, adoptive transfer of small numbers of ex vivo
      isolated TCR transgenic suppressor T cells allows for the visualization of the
      fate of such cells when confronted with cognate antigen in a quasi-normal,
      nonlymphopenic environment. Characteristic features of the currently available
      TCR transgenic models of suppressor T cells will be highlighted, and particular
      issues pertaining to the differentiation, function, and homeostasis of this T
      cell subset that have emerged from these models will be discussed.

PMID- 15981477
TI  - Migration rules: functional properties of naive and effector/memory-like
      regulatory T cell subsets.
AB  - Suppressor T cells were first described in the early 1970s, but since the
      hypothetical soluble suppressor factor could not be identified on a molecular
      level and since appropriate cellular markers were lacking, the suppressor T cell
      concept vanished for a long time. The discovery by Sakaguchi and co-workers, that
      the adoptive transfer of CD25+CD4+ -depleted T cells induced several organ
      specific autoimmune diseases in immunodeficient recipients, put the suppressor T
      cell model back into the focus of many immunologists. CD25+CD4+ T cells were
      named regulatory T cells (Treg) and since then have been intensively
      characterized by many groups. It has now been well documented in a variety of
      models that CD25+CD4+ Tregs, in addition to cell-intrinsic peripheral tolerance
      mechanisms such as anergy induction and peripheral deletion, play indispensable
      roles in the maintenance of natural self-tolerance, in averting autoimmune
      responses as well as in controlling inflammatory reactions. However, a number of
      fundamental questions concerning their origin, mechanism of action, and the sites
      of suppression remain elusive and are currently a matter of debate. Notably, the
      potential heterogeneity of Tregs with respect to phenotype and function deserves
      attention and is a major issue discussed in this review.

PMID- 15981478
TI  - Peripheral generation and function of CD4+CD25+ regulatory T cells.
AB  - The balance between immunity and tolerance is important to maintain immune
      homeostasis. Several mechanisms are in place to ensure that the immune response
      is controlled, such as T cell anergy, apoptosis and immune ignorance. A fourth
      mechanism of peripheral tolerance is the active suppression by regulatory or
      suppressor T cells. The existence of suppressor T cells was first described in
      the early 1970s, but these cells became discredited in the 1980s. The work of
      Shimon Sakaguchi and others, however, has brought these cells back into the
      limelight and nowadays research into regulatory/suppressor T cells is a very
      active field of immunology. Different types of regulatory T cells have been
      described, including CD4+CD25+ T cells that constitutively express CTLA-4, GITR
      and Foxp3, TGF-beta producing Th3 cells, IL-10 producing Tr1 cells, and CD8+CD28-
      T cells. This review will focus on the generation and function of CD4+CD25+
      regulatory T cells. CD4+CD25+ regulatory cells were originally described as
      thymus-derived anergic/suppressive T cells. Recent papers, however, indicate that
      these cells might also be generated in the periphery. CD4+CD25+ regulatory T
      cells can be activated by self-antigens and non-self-antigens, and once activated
      can suppress T cells in an antigen nonspecific manner. Interestingly, the
      suppressive effects of these cells are not restricted to the adaptive immune
      system (T and B cells) but can also affect the activation and function of innate
      immune cells (monocytes, macrophages, dendritic cells). These features make the
      CD4+CD25+ regulatory T cell subset an interesting target for immunotherapy of
      chronic inflammatory or autoimmune diseases.

PMID- 15981479
TI  - Dendritic cells: key cells for the induction of regulatory T cells?
AB  - Even though dendritic cells (DCs) are well known for their capacity to induce
      immune responses, recent results show that they are also involved in the
      induction of tolerance. These two contrary effects of otherwise homologous DCs on
      a developing immune response maybe explainedby different DC developmental stages,
      i.e., different subsets of DCs may exist and/or different spatial distribution of
      DCs in the body might influence their function. However, independently from the
      subtype(s), it is obvious that the ability of DCs to act in a tolerogenic fashion
      depends on the maturation status, since immature DCs are prone to induce
      regulatory T cells and hence promote tolerance, whereas mature DCs stimulate
      effector T cells, facilitating immunity. The means by which DCs convey tolerance
      are not entirely clear yet, but secretion of suppressive cytokines such as IL-10
      and induction of regulatory lymphocytes are involved. In this review we focus on
      the interaction between DCs and T cells and highlight some mechanisms in the
      decision-making process of whether immunity or tolerance is induced.

PMID- 15981480
TI  - Autoimmune gastritis is a well-defined autoimmune disease model for the study of
      CD4+CD25+ T cell-mediated suppression.
AB  - Autoimmune gastritis (AIG) is an experimental model that closely resembles human
      autoimmune gastritis, the underlying pathology of pernicious anemia. Pathogenic
      CD4+ T cells are reactive to the parietal cell autoantigen, H/K ATPase, and are
      controlled by CD4+CD25+ T cells in an immunosuppressive cytokine-independent
      manner. Comparison of CD4+CD25+ T cell-mediated suppression in other autoimmune
      models shows inconsistencies with respect to requirements of cytokines for
      immunosuppression. More recent data, however, indicate that the evidence for
      requirement of IL-10 and TGF-beta could be due to the complex nature of the T
      cells causing the disease as well as the role of induced regulatory T cell
      populations. AIG provides a well-defined model that may allow for better analysis
      of CD4+CD25+ T cell in vivo biology. Evidence from this model indicates that
      immune responses must be initiated and then CD4+CD25+ T cells are recruited to
      control the quality of the immune response.

PMID- 15981481
TI  - Regulatory T cells in experimental colitis.
AB  - Induction and maintenance of peripheral tolerance are important mechanisms to
      maintain the balance of the immune system. Growing evidence indicates that
      dysregulation of mucosal T cell responses may lead to loss of tolerance to
      commensal flora and to the development of inflammatory bowel diseases (IBD). Many
      studies suggest that active suppression of enteroantigen reactive cells mediated
      by regulatory T cells contributes to the maintenance of natural intestinal immune
      homeostasis. The use of the multiple animal models has not only improved our
      understanding of IBD, but also contributed to new suggestions of treatment
      strategies involving the use of regulatory T cells. The present review summarizes
      our current knowledge of regulatory T cells and their involvement in experimental
      IBD. The well-characterized SCID T cell transfer model and the naturally
      occurring regulatory CD4+CD25+ T cells are highlighted.

PMID- 15981482
TI  - Autoimmune ovarian disease in day 3-thymectomized mice: the neonatal time window,
      antigen specificity of disease suppression, and genetic control.
AB  - Discovery of the CD4+CD25+ T cells has stemmed from investigation of the AOD in
      the d3tx mice. Besides CD4+CD25+ T cell depletion, d3tx disease induction
      requires effector T cell activation prompted by lymphopenia. This is supported by
      other neonatal AOD models in which T cell-mediated injury has been found to be
      triggered by immune complex or Ag immunization. In addition, there is growing
      evidence that support a state of neonatal propensity to autoimmunity, which
      depends on concomitant endogenous antigenic stimulation, concomitant nematode
      infection, resistance to CD4+CD25+ T cell regulation, and participation of the
      neonatal innate system. The suppression of d3tx disease by polyclonal CD4+CD25+ T
      cells appears to be dependent on endogenous Ag and the persistence of regulatory
      T cells. Thus, suppression of AOD occurs in the ovarian LN, and AOD emerges upon
      ablation of the input regulatory T cells; and in AIP, the hormone-induced
      expression of prostate Ag in the CD4+CD25+ T cell donors rapidly enhances the
      capacity to suppress disease over Ag negative donors. Finally, genetic analysis
      of AOD and its component phenotypes has uncovered seven Aod loci. As the general
      themes that emerged, significant epistatic interactions among the loci play a
      role in controlling disease susceptibility, the majority of the Aod loci are
      linked to susceptibility loci of other autoimmune diseases, and the genetic
      intervals encompass candidate genes that are differentially expressed between
      CD4+CD25+ T cells and other T cells. The candidate genes include Pdcd1, TNFR
      superfamily genes, H2, Il2, Tgfb, Nalp5 or Mater, an oocyte autoAg that reacts
      with autoantibody in sera of d3tx mice.

PMID- 15981483
TI  - Regulatory T cells in transplantation tolerance.
AB  - Our ability to harness tolerance mechanisms will have a major impact in organ
      transplantation if it becomes possible to minimize drug maintenance, or even wean
      off immunosuppressive drugs. An improved understanding of the biology of
      regulatory T cells will make it possible to replace current induction regimens
      with those favouring the vaccination and selection of T cells that prevent graft
      rejection. Once tolerance is established, the continuous supply of graft antigens
      should sustain T cell mediated regulation as the dominant mechanism preventing
      graft rejection.

PMID- 15981484
TI  - CD4+CD25+ regulatory T cells in hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (SCT) is a well-established
      treatment modality for malignant and nonmalignant hematologic diseases. High-dose
      radio- and/or chemotherapy eradicate the hematopoietic system of the patient and
      induce sufficient immunosuppression to enable donor stem cell engraftment. The
      replacement of the recipient's immune system with that of the donor significantly
      contributes to the success of this treatment, since donor immune cells facilitate
      stem cell engraftment, provide protection from infections, and eliminate residual
      malignant or nonmalignant host hematopoiesis, thereby protecting from disease
      relapse in patients transplanted for leukemia or lymphoma (graft-versus-leukemia
      effect, GVL). Mediators of these beneficial effects are mature T cells within the
      stem cell graft. However, donor T cells can also attack host tissues and induce a
      life-threatening syndrome called graft-versus-host disease (GVHD). The challenge
      of allogeneic SCT is to find a balance between beneficial and harmful T cell
      effects, which at present is only insufficiently achieved by the use of
      immunosuppressive drugs. In the future, it might be possible to replace or
      support such medications by using the intrinsic regulatory capacity of the
      transplanted immune system, as represented by T cell subpopulations with
      suppressive activity, such as CD4+ CD25+ regulatory T (Treg) cells. In various
      mouse model systems, these cells have been shown to suppress GVHD while
      preserving the GVL effect. As the characterization of their human counterparts is
      rapidly progressing, their application in allogeneic SCT might soon be explored
      in clinical trials.

PMID- 15981485
TI  - Naturally arising CD25+CD4+ regulatory T cells in tumor immunity.
AB  - Naturally arising regulatory T (TR) cells, represented by CD25+CD4+ TR cells,
      play an essential role in maintaining immunological self-tolerance. This T cell
      mediated dominant control of the immune response not only inhibits the
      development of autoimmune disease, but also impedes effective immunosurveillance
      against autologous tumor cells. Attenuation of TR cell-mediated immune
      suppression can therefore evoke effective tumor immunity in otherwise
      nonresponsive animals. This common regulatory mechanism for autoimmunity and
      tumor immunity can be exploited when devising a novel immunotherapy for cancer.

PMID- 15981486
TI  - Phenotypic and functional differences between human CD4+CD25+ and type 1
      regulatory T cells.
AB  - T regulatory (Tr) cells have an essential role in the induction and maintenance
      of tolerance to both and foreign self-antigens. Many types of T cells with
      regulatory activity have been described in mice and humans, and those within the
      CD4+ subset have been extensively characterized. CD4+ Type-1 regulatory T (Tr1)
      cells produce high levels of IL-10 and mediate IL-10-dependent suppression,
      whereas the effects of naturally occurring CD4+CD25+ Tr cells appear to be cell
      contact-dependent. Tr1 cells arise in the periphery upon encountering antigen in
      a tolerogenic environment. In contrast, it appears that CD4+CD25+ Tr cells can
      either arise directly in the thymus or be induced by antigen in the periphery. We
      have been interested in defining the phenotype and function of different subsets
      of CD4+ Tr cells present in human peripheral blood, with the ultimate aim of
      designing therapeutic strategies to harness their immunoregulatory effects. This
      review will discuss the similarities and differences between human Tr1 and
      naturally occurring CD4+CD25+ Tr cells, as well as evidence that indicates that
      they have nonoverlapping, but synergistic roles in immune homeostasis.

PMID- 15981487
TI  - [Changes of physiological intraocular pressure (IOP) in rabbits after
      administration of the amino acid lysine and the antiglaucoma drug latanoprost
      (Xalatan)].
AB  - PURPOSE: To show and underline specific character of influence of the mixture of
      10% L-lysine.2HCl.2H2O in 0.005% latanoprost on physiological levels of IOP.
      METHODS: The mixture of 10% L-lysine.2HCl.2H2O in 0.005 % latanoprost (Xalatan),
      or separately 0.005 % latanoprost and 10% L-lysine.2HCl.2H2O respectively were in
      weekly intervals instilled into the conjunctival sac of the left eye of five
      rabbits (females of "New Zealand white" bred). The IOP levels and the size of the
      pupil were measured in minute 5, 15, 30, 60, 120, 180, and 240 after the
      instillation. The right eye was considered as a control. RESULTS: The amino acid
      L-lysine.2HCl.2H2O by itself did not influence the IOP or the size of the pupil;
      latanoprost until minute 30 lowered the IOP, in minute 55 exceeds the IOP the
      level of the control eye. Since minute 60 until 240, the IOP changed irregularly
      and insignificantly. The mixture of 10% solution of L-lysine.2HCl.2H2O in
      latanoprost 0.005% insignificantly lowered the IOP until min. 30, after rapid
      elevation in min. 50 exceeds the IOP of the control eye, and since min. 60, the
      IOP remains above the control eye's IOP with the same course of levels. SUMMARY:
      The amino acid L-lysine.2HCl.2H2O alone did not change the physiological IOP.
      Latanoprost 0.005% significantly lowered the IOP until min. 30. High level of
      interactive specificity as well as duration of influence of the mixture of
      respective amino acid with respective antiglaucomatic drug was established.

PMID- 15981488
TI  - [Transpupillary thermotherapy in exsudative age-related macular degeneration. Two
      years results and findings on the other eye].
AB  - The purpose of the prospective randomized study was to analyze long-term results
      of transpupillary thermotherapy (TTT) in exsudative age-related macular
      degeneration (ARMD) after 24 months of follow-up and to compare them with
      findings on the other, not treated eye. MATERIAL AND METHODS: Seventy-two
      patients aged 50-93 years (average age 70.6 years) with one eye treated by means
      of TTT and the other considered as control were in the study. Occult choroidal
      neovascularization (CNV) was treated in 33 eyes (45.8%), serous ablation of the
      pigment epithelium (SAPE) in 21 eyes (29.2%), and classical CNV in 18 eyes
      (25.0%). In all patients, the central visual acuity (VA) on EDTRS chart was
      specified, the macular findings were observed by means of indirect binocular
      ophthalmoscope and bio-microscopically with the contact lens on the slit lamp,
      and fluorescence angiography and optical coherence tomography (OCT) examinations
      were performed before and 3, 6, 12, 18, and 24 months after the TTT treatment.
      RESULTS: The final VA improved or remained unchanged in 27 eyes (37.5%), and
      worsened in 45 eyes (62.5%), by 5 or more lines the VA worsened in 19 eyes
      (26.4%). The average VA decreased from initial 0.24 to final 0.13, but the
      decrease in different forms of ARMD varied. In SAPE the highest initial as well
      as final average VA was found, in occult and classical CNV the initial and final
      average VA was almost identical. Exsudative changes observed by means of
      biomicroscopical, fluoroangiographical, and OCT examinations totally disappeared
      in 59.7%, 63.9%, and 59.7% respectively. At the end of the follow-up period we
      observed chorioretinal atrophy of different stage in the macula in all eyes
      (100%) and subretinal fibrosis in 44 eyes (61.7%). Both these findings
      represented final stages of natural course of exsudative ARMD. On the contrary,
      differently pronounced areas of chorioretinal atrophy corresponding with applied
      laser burns represented scars after the coagulation. It developed in 31 eyes
      (43.0 %) and pointed to the possible destructive consequence of the TTT. In 33
      patients (45.8%), late stages of exsudative ARMD, mostly disciform scars with
      chorioretinal atrophy were found on the other not treated eye. In these eyes the
      final average VA was 0.05, e.g. more than one half worse than final average VA in
      treated eyes. CONCLUSIONS: Results of TTT treatment after 24 month of follow-up
      demonstrated full regression of exsudative changes in the macula in 60% of eyes
      and improved or stable VA in 37.5 % of eyes. Results in SAPE and classical CNV
      confirmed the efficacy of TTT treatment in those forms of ARMD. The TTT did not
      prevent the appearance and progress of the chorioretinal atrophy and subretinal
      fibrosis, causing the main obstacle of better functional results. Extremely
      unfavorable course of exsudative ARMD in the other (not treated) eye could
      indirectly confirm the positive influence of the TTT in theARMD treatment.
      Despite all positives are the possibilities of the TTT limited and determined by
      the basis and natural course of exsudative ARMD.

PMID- 15981489
TI  - [The results of radiotherapy 24 months after treatment by patients with age
      related macular degeneration].
AB  - The authors evaluate results of the radiotherapy by age- related macular
      degeneration. 114 patients (123 eyes) were examined. According to the total dose,
      we have divided the patients in 3 groups. Group A (12 Gy) consisted of 68
      patients (74 eyes) and group B consisted of 46 patients (49 eyes), group C was
      designated as a control group, consisting of 21 patients (22 eyes). They have
      been performed in Department of Ophthalmology of Teaching Hospital of Charles
      University in Hradec Kralove from February 1999 to April 2003. All examinations
      were performed before and at 24 months- follow up the radiotherapy. Radiotherapy
      seems to be a very promising and efficient method for treatment of the wet form
      of ARMD.

PMID- 15981490
TI  - [Perforating pars plana sclerotomy in idiopathic uveal effusion syndrome].
AB  - PURPOSE: To evaluate anatomical and functional results of perforating pars plana
      sclerotomy in 2 patients with the idiopathic uveal effusion syndrome (IUES).
      METHODS: In two patients with IUES the perforating pars plana sclerotomy was
      performed. During the surgery samples of the suprachoroidal fluid for biochemical
      analysis of protein fractions were taken. RESULTS: During the follow-up period
      (average 4 years) the retina and the choroid attached, and the central visual
      acuity (VA) improved as well in both patients. CONCLUSION: In IUES, the
      conservative treatment is not effective. Perforating pars plana sclerotomy is
      treatment of choice and it had positive anatomical and functional effect in both
      our patients with IUES.

PMID- 15981491
TI  - [Terson's syndrome, pars plana vitrectomy and anatomical and functional outcome].
AB  - The retrospective case review was aimed to demonstrate anatomical and functional
      results of pars plana vitrectomy (PPV) in patients with Terson's syndrome (TS).
      The most common cause of TS was an acute subarachnoid hemorrhage of ruptured
      intracranial aneurysm (6 eyes). One patient suffered traumatic subdural and
      subarachnoid hemorrhage. PPV was performed in 7 eyes of 6 patients (2 women and 4
      men). The patients ranged in age from 18 to 53 years (average 37.5 year), the
      mean age was 37.5 years. The interval between intracranial hemorrhage and PPV
      varied from 2 to 12 month (average 7.5 months). The visual acuity postoperatively
      improved in all 7 eyes. The mean period of observation was 12.5 month.
      Intraoperative complications included retinal break (1) only. Late complications
      included epiretinal membrane (2), glaucoma (1), cataract (2) and conjunctival
      cyst (1). Pars plana vitrectomy is highly effective and relatively safe method in
      hastening visual rehabilitation of adults with Terson's syndrome.

PMID- 15981492
TI  - [Surgical treatment of late tractional retinal detachment appearing on the basis
      of retinopathy of prematurity].
AB  - Retinopathy of prematurity (ROP) is a proliferative retinopathy affecting
      predominantly immature children and children with low birth weight under 2500 g
      in 5-6%. During 11 years we operated on 15 eyes of 15 patients aged 5-31 years,
      because of late tractional retinal detachment (TRD) appearing on the basis of
      ROP. The average follow-up period was 37.2 months; the minimal follow-up period
      was 1 year. In all patients, the personal medical history revealed the pre-term
      birth at the gestation age of 28-34 weeks. The birth weight was in the range 850
      1600 grams. According to the extend of vitreoretinal traction and type of retinal
      defect we indicated: a) primary cryosurgical procedure (CP) with episcleral
      silicone implants. The operation was indicated in 6 eyes: cerclage, segmental
      perilimbal plombage in the temporal half and puncture of the subretinal fluid; b)
      pars plana vitrectomy (PPV). In total in 9 eyes the PPV was indicated, in 5 eyes
      it was supplemented with relaxing retinotomy, and in 7 eyes with silicone oil
      (SO) implantation. Three eyes were re-operated by means of PPV with SO
      implantation. The final anatomical success of the surgical treatment of the
      prognostic unfavorable TRD, including re-operations was achieved in 12 eyes
      (80%), which we consider as a good one. The visual acuity improved or remained
      the same also in 12 eyes (80%) and visual acuity 6/60 and better (20/200 or 0.1)
      in 8 out of 15 eyes (53%).

PMID- 15981493
TI  - [Comparison of accuracy of refraction measurement in children up to the age of 15
      years using the PowerRef II and by standard techniques].
AB  - OBJECTIVE: To establish whether refraction state in children up to the age of 15
      years measured by photorefraction using PowerRef II device is comparable with
      values measured using common methods like skiascopy and autorefractor.
      Photorefraction is a quick method to determine refractive state from a distance
      without mydriasis and simultaneously in both eyes. It appears, therefore, to be a
      useful tool for measuring refractive errors of infants and older noncooperative
      subjects. However, its accuracy and reliability has been discussed. METHODS: In
      this study the authors assess accuracy of measurement of refractive errors by
      photorefraction in 40 children (19 boys, 21 girls) at the age ranging from 4
      month to 15 years (average 4.8 years), divided according to their cooperation
      into two groups. The values of refraction acquired by photorefraction using
      PowerRef II device were compared with skiascopy in 23 noncooperative infants and
      with values of refraction from common autorefractor Nidek AR 600 in 17
      cooperating children. RESULTS: Comparing results of both groups we have detected
      an average difference 0.41 D between skiascopy and photorefraction for spherical
      equivalents (0.45 for spheres, 0.42 for cylinders), average difference between
      spherical equivalents from autorefractor and photorefractor measurements was
      comparable: 0.52 D (0.51 for spheres, 0.55 for cylinders). CONCLUSION:
      Refractions measured by eccentric photorefraction with PowerRef II were
      comparable to those obtained by common methods of refraction measurement in
      children--i.e. skiascopy and autorefractor. Values of refraction were undervalued
      only in two cases of higher myopia during photorefraction measurement compared to
      autorefractor values. There was no significant shift by photorefraction
      measurement to myopic or hypermetropic values.

PMID- 15981494
TI  - [Effect of refraction procedures (LASIK) on various ocular functions (initial
      results)].
AB  - PURPOSE: to determine effect of laser in situ keratomileusis (LASIK) on visual
      functions: visual acuity (VA) and contrast sensitivity (CS). PATIENTS AND
      METHODS: Prospective study includes results of VA and CS preoperatively and 1, 3
      and 6 months postoperatively in patients with middle and high myopia. 36 eyes of
      18 patients (3 men and 15 women) were divided according to spherical equivalent
      into 2 groups: group A (> -5.0 D, 18 eyes) and group B (< -5.0 D, 18 eyes). Mean
      patient's age was 27 years (range 19-46 years). Visual acuity was measured on
      logMAR charts, contrast sensitivity at 3, 6, 12 and 18 c/deg was tested using CSV
      1000 Contrast sensitivity unit. In both groups, results of preoperative best
      corrected visual acuity (BCVA) were compared to uncorrected visual acuity (UCVA)
      after surgery. RESULTS: Visual acuity preoperatively was significantly decreased
      in comparison to controls in both groups, considerable decrease can be detected
      at 1 month postoperatively and it returns to preoperative values during 6 months
      after surgery. Postoperatively, a significant decrease of CS can be detected,
      above all at intermediate spatial frequencies. During first 6 months, values of
      CS slowly increase in both groups. However, only in group B (< -5D) the
      preoperative values have been reached. CONCLUSIONS: Our study suggests that both
      used methods are very sensitive for evaluation of visual functions after
      refractive surgery. Changes of contrast sensitivity reveal even slightly changed
      optic factors of cornea that can cause subjective complaints of patients.

PMID- 15981496
TI  - [Congenital stationary night blindness (CSNB)--a case report].
AB  - PURPOSE: To document occurrence of the congenital stationary night blindness type
      Schubert-Bornschein in some members of one family, to put together the family
      tree, and to evaluate the examination methods. Among others the electroretinogram
      (ERG) is substantial in the diagnosis of the disease and to distinguish different
      types of CSNB. In the affected family, only in men the disease is expressed,
      females are transmitters. This corresponds to the X-linked inheritance.
      Simultaneously with CSNB, in this family, high myopia occurs not only in men, but
      also in women. CONCLUSION: CSNB is an inherited disease, mostly with X-linked
      inheritance. Affected are predominantly males, females are transmitters. This
      disease is not possible to treat. Despite this, to determine proper diagnosis is
      important and use of ERG is mandatory.

PMID- 15981495
TI  - [Spontaneous late subluxation of capsule, intraocular lens and capsular ring in
      patient with pseudoexfoliation syndrome--a case report].
AB  - The authors present a case of spontaneous late subluxation of capsule,
      intraocular lens and capsular ring in patient with pseudoexfoliation syndrome. A
      78-year old woman was operated (phacoemulsification, implantation of capsular
      tension ring and intraocular lens) in the left eye in June 2001 and the same
      procedure was performed in the right eye in September 2001. No early
      postoperative complicantions were encountered. The patient was referred with
      vision reduction in the left eye in May 2004. Biomicroscopy revealed inferior
      dislocation of the capsular bag, capsular ring, and intraocular lens.
      Explantation of the whole complex and secondary anterior chamber lens was
      provided. The postoperative course was uneventful, and visual functions improved.

PMID- 15981497
TI  - [The first head of the ophthalmology department in Kromerizi, Jaroslav Hulka, and
      his plans for ophthalmology education in Czechoslovakia after World War II].

PMID- 15981498
TI  - Closed-loop experimental validation of the spatially filtered Shack-Hartmann
      concept.
AB  - An experimental validation of the spatially filtered Shack-Hartmann concept (F
      SH) is presented that allows aliasing effects to be decreased. This effect is
      studied by use of an adaptive optical testbed with a focal plane pinhole in front
      of the wave-front sensor. First, the ability to close the loop on turbulence is
      demonstrated. Then the performance gain conferred by the device is quantified and
      compared with end-to-end simulation results. Another property of the F-SH
      concept, i.e., the reduction of the waffle modes, is highlighted.

PMID- 15981499
TI  - Influence of the short-range coordination order of erbium ions on excitation
      migration and upconversion in multicomponent glasses.
AB  - Applying a pair-correlation function of erbium ions that is known from x-ray
      absorption fine structure spectroscopy, we develop a new statistical model of
      migration-assisted upconversion in erbium-doped glasses. The results of modeling
      show that short-range coordination order of erbium ions contributes to the
      upconversion rate for both low and high population inversion. In addition, we
      report the methods of suppression of the short-range order of erbium ions in
      multicomponent glasses.

PMID- 15981500
TI  - Pump-induced nonlinear refractive-index change in erbium- and ytterbium-doped
      fibers: theory and experiment.
AB  - A 980-nm pump-induced nonlinear refractive-index (n2) change in erbium-doped (20
      m) and ytterbium-doped (20-m) fibers has been measured at 1064 nm by time-delayed
      photorefractive beam coupling in a co-propagating and counterpropagating
      geometry. It was found that n2 decreases at the wavelength of the probe beam when
      the pump beam is present. We present a semiclassical theory based on a four-state
      system that accounts for the pump-induced change of n2. Both theoretical and
      experimental results show that a significant index change, of the order of 10%,
      can be obtained for cw pump powers as small as 10 mW.

PMID- 15981501
TI  - Second mode transition in microstructured optical fibers: determination of the
      critical geometrical parameter and study of the matrix refractive index and
      effects of cladding size.
AB  - We carried out a numerical study of the second mode transition in finite-sized,
      microstructured optical fibers (MOFs) for several values of the matrix refractive
      index. We determined a unique critical geometrical parameter for the second mode
      cutoff that is valid for all the matrix refractive indices studied. Finite size
      effects and extrapolated results for infinite structures are described. Using
      scaling laws, we provide a generalized phase diagram for solid-core MOFs that is
      valid for all refractive indices, including those of the promising chalcogenide
      MOFs.

PMID- 15981502
TI  - Use of 1-m Bi2O3 nonlinear fiber for 160-Gbit/s optical time-division
      demultiplexing based on polarization rotation and a wavelength shift induced by
      cross-phase modulation.
AB  - We present, for the first time to our knowledge, experimental results of the use
      of a 1-m-long Bi2O3-based nonlinear fiber (Bi-NLF) with a nonlinear parameter
      gamma of approximately 1100 W(-1) km(-l) within an all-fiber-based 160Gbit/s
      optical time-division multiplexing (OTDM) data demultiplexer. Our demultiplexing
      switch basically uses the principle of the Kerr shutter, and its switching
      performance is further enhanced by the additional use of the wavelength blueshift
      of data pulses, which is induced by cross-phase modulation from the control
      pulse's trailing edge. The OTDM demultiplexer, composed of the 1-m Bi-NLF,
      readily achieves error-free demultiplexing operation of all 16 channels.

PMID- 15981503
TI  - Synthesis of MFI zeolite films on optical fibers for detection of chemical
      vapors.
AB  - We report the development of a novel zeolite-incorporated optical fiber sensor
      and demonstrate its capability for in situ detection of chemical vapors. The
      sensor comprises a polycrystalline silicalite thin film grown upon the cleaved
      end face of a standard single-mode optical fiber. The sensor device operates by
      measuring the optical reflectivity of the zeolite crystals, which changes
      reversibly in response to the amount of chemical vapor adsorbed in its
      crystalline microporous structure. The sensor has been successfully demonstrated
      for measuring the concentration of isopropanol vapor in mixtures with nitrogen
      gas.

PMID- 15981504
TI  - Evanescent field-based optical fiber sensing device for measuring the refractive
      index of liquids in microfluidic channels.
AB  - We report a simple optical sensing device capable of measuring the refractive
      index of liquids propagating in microfluidic channels. The sensor is based on a
      single-mode optical fiber that is tapered to submicrometer dimensions and
      immersed in a transparent curable soft polymer. A channel for liquid analyte is
      created in the immediate vicinity of the taper waist. Light propagating through
      the tapered section of the fiber extends into the channel, making the optical
      loss in the system sensitive to the refractive-index difference between the
      polymer and the liquid. The fabrication process and testing of the prototype
      sensing devices are described. The sensor can operate both as a highly responsive
      on-off device and in the continuous measurement mode, with an estimated accuracy
      of refractive-index measurement of approximately 5 x 10(-4).

PMID- 15981505
TI  - Simultaneous temperature and strain measurement with combined spontaneous Raman
      and Brillouin scattering.
AB  - We report on a novel method for simultaneous distributed measurement of
      temperature and strain based on spatially resolving both spontaneous Raman and
      Brillouin backscattered anti-Stokes signals. The magnitude of the intensity of
      the anti-Stokes Raman signal permits the determination of the temperature. The
      Brillouin frequency shift is dependent on both the temperature and the strain of
      the fiber; once the temperature has been determined from the Raman signal, the
      strain can then be computed from the frequency measurement of the Brillouin
      signal.

PMID- 15981506
TI  - Rewritable densification gratings in boron-doped fibers.
AB  - We show that the strength of long-period gratings recorded in boron-doped fibers
      by CO2 radiation can be significantly enhanced by a uniform pre-exposure by the
      same laser. The resultant gratings could be erased by a similar uniform exposure
      and then recorded again multiple times with no loss of fiber sensitivity. We
      suggest that such gratings are formed by reversible densification of the fiber
      core. These densification gratings have higher thermal stability than gratings
      written with ultraviolet light.

PMID- 15981507
TI  - Multiwavelength Raman-fiber-laser-based long-distance remote sensor for
      simultaneous measurement of strain and temperature.
AB  - We propose a simple and flexible multiwavelength Raman-fiber-laser-based long
      distance remote-sensing scheme for simultaneous measurement of strain and
      temperature by use of fiber Bragg gratings. By combining two uniform fiber Bragg
      gratings with a tunable chirped fiber grating, we readily achieve simultaneous
      two-channel sensing probes with a high extinction ratio of more than
      approximately 50 dB over a 50-km distance. When strain and temperature are
      applied, lasing wavelength separation and shift occur, respectively, since the
      two uniform fiber Bragg gratings have identical material composition and
      different cladding diameters. This allows simultaneous measurement of strain and
      temperature for long-distance sensing applications of more than 50 km.

PMID- 15981508
TI  - High extinction ratio in-fiber polarizers based on 45 degree tilted fiber Bragg
      gratings.
AB  - We report a near-ideal in-fiber polarizer implemented by use of 45 degrees tilted
      fiber Bragg grating structures that are UV inscribed in hydrogenated Ge-doped
      fiber. We demonstrate a polarization-extinction ratio of 33 dB over a 100-nm
      operation range near 1550 nm. We further show an achievement of 99.5% degree of
      polarization for unpolarized light with these gratings. We also theoretically
      investigate tilted grating structures based on the Green's function calculation,
      therein revealing the unique polarization characteristics, which are in excellent
      agreement with experimental data.

PMID- 15981509
TI  - Photon echoes in an amplifying rare-earth-ion-doped crystal.
AB  - We report what we believe is the first experimental demonstration of photon
      echoes in an amplifying rare-earth-ion-doped crystal. Population inversion is
      achieved by optical pumping, which yields high-power photon echoes, with an
      energy gain of as much as a factor of 5. Effects of the pump on the photon echo
      process highlight the advantages of an amplifying crystal. New questions
      concerning the optical dephasing mechanisms in Er3+:YSO have arisen.

PMID- 15981510
TI  - Superhigh numerical aperture (NA > 1.5) micro gradient-index lens based on a dual
      material approach.
AB  - We describe a novel scheme for obtaining a superhigh numerical aperture gradient
      index (SHNA GRIN) lens from multiple thin layers of two or more materials with
      large refractive-index contrast. Design procedures for the lens are described,
      including variation of the layer thickness to achieve focusing and of the
      thickness limit to reduce scattering loss. We use an exact numerical solution by
      the finite-difference time-domain method to evaluate the lens's performance.
      Specific examples of a SHNA GRIN lens with a SiO2-TiO2 material system designed
      for fiber coupling to a nanowaveguide are shown to have focusing FWHM spot sizes
      of 0.53-0.7 microm at lambda =1.55 microm (corresponding to a NA of approximately
      1.6-1.1) with 2.7-2.4% more loss than an ideal continuous index profile GRIN
      lens. With this approach, a SHNA GRIN lens with a NA of > 1.5 and a length of <20
      microm can be achieved with currently available thin-film deposition techniques.

PMID- 15981511
TI  - Chaotic imaging in frequency downconversion.
AB  - We analyze and recover, by means of spatial intensity correlations, the image
      obtained by a seeded frequency-downconversion process in which the seed field is
      chaotic and an intensity modulation is encoded in the pump field. Although the
      field generated is as chaotic as the seed field and does not carry any
      information about the modulation of the pump, one can extract an image of the
      pump by measuring the spatial intensity correlations between the generated field
      and one Fourier component of the seed.

PMID- 15981512
TI  - High-resolution volume holographic profilometry using the Viterbi algorithm.
AB  - We use the Viterbi decoding algorithm to resolve depth features beyond the
      nominal resolution limit of a volume holographic profilometry system. The
      formulation treats the truncated point-spread function as an intersymbol
      interference and uses surface constraints and transition constraints to reduce
      the computational complexity. A factor-of-5 improvement in resolution was
      obtained in our experimental demonstration.

PMID- 15981513
TI  - Nonplanar photolithography with computer-generated holograms.
AB  - We outline a method for accomplishing photolithography on grossly nonplanar
      substrates. First we compute an approximation of the diffraction pattern that
      will produce the desired light-intensity distribution on the substrate to be
      patterned. This pattern is then digitized and converted into a format suitable
      for manufacture by a direct-write method. The resultant computer-generated
      hologram mask is then used in a custom alignment tool to expose the photoresist
      coated substrate. The technique has many potential applications in the packaging
      of microelectronics and microelectromechanical systems.

PMID- 15981514
TI  - Depth-of-focus reduction for digital in-line holography of particle fields.
AB  - Poor axial precision caused, in part, by large depth of focus (tau) has been a
      vexing problem in extraction of particle position from digital in-line holograms.
      A simple method is proposed to combat this depth-of-focus difficulty. The method
      is based on decoupling of size and position information. With d, Delta, and
      lambda being particle diameter, CCD pixel size, and the wavelength, respectively,
      our main theoretical result is the reduction of tau from tau - d2/lambda to tau -
      Delta2/lambda for particles of known size. This result is confirmed in laboratory
      experiments with holograms of calibrated glass spheres.

PMID- 15981515
TI  - Multiple-image encryption by wavelength multiplexing.
AB  - We introduce the technique of wavelength multiplexing into a double random-phase
      encoding system to achieve multiple-image encryption. Each primary image is first
      encrypted by the double phase encoding method and then superposed to yield the
      final enciphered image. We analyze the minimum separation between two adjacent
      multiplexing wavelengths through cross talk and the multiplexing capacity through
      the correlation coefficient. Computer simulations are performed to demonstrate
      the concept. This technique can be used for hiding multiple images as well.

PMID- 15981516
TI  - Self-deconvolution for shift-and-add imaging.
AB  - A shift-and-add (SAA) method is used to restore atmospherically degraded images.
      The operation of the SAA method is simple, but the deconvolution method of SAA
      images remains to be developed, especially for extended objects. We propose to
      deconvolve a SAA image of an extended object by use of a self-deconvolving data
      reconstruction algorithm (SeDDaRA). Computer simulations show the effectiveness
      of the SeDDaRA to SAA images. It is also shown that use of the SAA method after
      each data frame is self-deconvolved leads to a better reconstruction.

PMID- 15981517
TI  - Wave-front spacing in the focal region of high-numerical-aperture systems.
AB  - The wave-front spacing in the focal region of an aplanatic focusing system is
      investigated by use of the vector theory of electromagnetic diffraction for
      monochromatic, linearly polarized incident light. It is shown that, in systems of
      high numerical aperture, the wave-front spacing near the focus is significantly
      larger than the wavelength of the incident light and that the wave-front spacing
      changes significantly within a few wavelengths of the focus and can be less than
      a wavelength.

PMID- 15981518
TI  - Effect of multiple laser irradiations on silica at 1064 and 355 nm.
AB  - We analyze laser damage precursor evolution under multiple irradiations by
      changing test parameters such as shot number, wavelength, shot frequency, and
      test location (bulk or surface). The experimental data exhibit different
      behaviors under repetitive shots regarding the damage precursor densities and
      thresholds. The results provide new information for understanding the laser
      damage initiation process in silica. Furthermore, the data permit us to predict
      the lifetime of optical components under multiple irradiations.

PMID- 15981519
TI  - Measurement of the effective focal shift in an optical trap.
AB  - The focus of an oil-immersion microscope objective is shifted because of the
      refractive-index mismatch between the cover glass and the aqueous sample. We
      present a procedure with which to determine the focal shift by use of an inverted
      microscope equipped with optical tweezers. As the position of the sample chamber
      is scanned vertically, we measure the axial displacement of an optically trapped
      bead; the relative motion of the bead with respect to the surface supplies the
      effective focal shift. Measurements of this quantity deviate from electromagnetic
      calculations of the focal shift, a discrepancy attributable to the depth
      dependent decrease in axial trap stiffness that arises from spherical aberration.

PMID- 15981520
TI  - Diode-laser-based ultraviolet-absorption sensor for high-speed detection of the
      hydroxyl radical.
AB  - A new diode-laser-based UV-absorption sensor for high-speed detection of the
      hydroxyl radical (OH) is described. The sensor is based on sum-frequency
      generation of UV radiation at 313.5 nm by mixing the output of a 763-nm
      distributed-feedback diode laser with that of a 532-nm high-power, diode-pumped,
      frequency-doubled Nd:YVO4 laser in a beta-barium borate crystal. Approximately 25
      microW of UV radiation is generated and used to probe rotational transitions in
      the A2 Sigma+ -X2II (v' = 0, v" = 0) electronic transition of OH. Single-sweep,
      single-pass measurements of temperature and OH concentration in a stoichiometric
      C2H4-air flame are demonstrated at rates up to 20 kHz.

PMID- 15981521
TI  - Highly repeatable all-solid-state polarization-state generator.
AB  - We report an all solid-state polarization-state generator that uses magneto-optic
      polarization rotators. The device can generate either five or six distinctive
      polarization states uniformly across a Poincare sphere with repeatability better
      than 0.1 degrees. It is ideal for polarization analysis, swept-wavelength
      measurement, and monitoring of polarization-related parameters and signal-to
      noise ratios of optical networks.

PMID- 15981522
TI  - Complete single-photon counting and timing module in a microchip.
AB  - A complete module for single-photon counting and timing is demonstrated in a
      single chip. Features comparable with or better than commercially available
      macroscopic modules are obtained by integration of an active-quenching and active
      reset circuit in complementary metal-oxide semiconductor technology together with
      a single-photon avalanche diode (SPAD). The integrated SPAD has a 12-microm
      diameter sensitive area and operates with an overvoltage above breakdown
      adjustable up to 20 V. With a 5-V overvoltage the photon detection efficiency
      peaks above 40% around 500 nm, and the dark-counting rate is lower than 600
      counts/s at room temperature. The overall counting dead time is 33 ns.

PMID- 15981523
TI  - Efficient terahertz coupling lens based on planar photonic crystals on silicon on
      insulator.
AB  - We present a promising coupling device, namely, a terahertz (THz) planar photonic
      crystal (PhC) lens based on the effective refractive-index contrast between the
      PhC and the surrounding unpatterned area. Three-dimensional finite-difference
      time-domain calculations show a 90% power transfer from a 100-microm silicon
      waveguide to a 10-microm waveguide, and 45% coupling efficiency is confirmed
      experimentally. These results demonstrate the utility of the PhC lens as an
      effective approach to coupling into PhC THz circuits.

PMID- 15981524
TI  - Optical waveguides structured with photoaligning polymers.
AB  - We present a novel fast fabrication method for making optical waveguides by using
      a photoaligning and a liquid-crystal polymer. A difference in the refractive
      indices in the core and cladding regions is achieved by use of polarized UV light
      to align the polymer chains differently. A refractive-index difference of Deltan
      = 0.07 was achieved. The propagation loss in a channel waveguide is 4 dB/cm at a
      wavelength of 1.55 microm. The fabrication method has only a few processing steps
      and yields short fabrication times. The waveguide structures offer possibilities
      for generating devices with new applications related to the polarization of the
      guided light.

PMID- 15981525
TI  - Coherence effects in surface roughness induced by vacuum ultraviolet F2 laser
      ablation.
AB  - We analyze statistical fluctuations in the pulse-to-pulse spatial fluence
      distribution of a highly multimode F2 laser beam and the influence that coherence
      effects have on the attainable smoothness of an ablated surface. The magnitude of
      fluctuations is predicted to be a few percent, with associated roughness
      increasing as m1/2, where m is the number of ablation pulses. By use of a white
      light optical interferometer, measurements have been made of roughness induced on
      N-BK7 glass surfaces ablated with a 157-nm laser, and reasonable agreement with
      predictions based on this roughening mechanism has been found.

PMID- 15981526
TI  - Self-organized coherence in fiber laser arrays.
AB  - We report the production of stable, coherent, and same-phase states in arrays of
      fiber lasers. Provided that proper interactions between the lasers are present,
      arrays will spontaneously self-organize into stable coherent same-phase states.
      There is no need for active control. Power scaling, power spectra, spatial
      interference fringes, and temporal data all support this conclusion.

PMID- 15981527
TI  - Spectrally narrowed external-cavity high-power stack of laser diode arrays.
AB  - We describe an effective external cavity for narrowing the spectral linewidth of
      a multiarray stack of laser diode arrays. For a commercially available 279-W free
      running five-array laser diode array operating at 60 A, we narrow the spectral
      linewidth to 0.40 nm at FWHM with 115 W of cw power output. This technique leads
      to the possibility of higher-efficiency, lower-cost production of hyperpolarized
      noble gases for magnetic resonance imaging.

PMID- 15981528
TI  - Laser emission with low quantum defect in Yb: CaGdAlO4.
AB  - It is demonstrated that 2% Yb: CaGdAlO4 (called CAlGO) presents favorable
      thermomechanical properties with a high measured thermal conductivity (Kc = 6.3
      and Kc = 6.9 W m(-1) K(-1). A laser oscillation in this material at 1016 nm is
      demonstrated for the first time to our knowledge while pumping at 979 nm. This
      implies a very small quantum defect (3.5%). A simple new figure of merit that
      takes into account thermomechanical properties and quantum defects is proposed
      here to compare the resistance of materials under high-power laser pumping.
      Consequently, Yb:CAlGO is similar to garnets and sesquioxides in regard to laser
      power resistance.

PMID- 15981529
TI  - Magnetic response of split-ring resonators in the far-infrared frequency regime.
AB  - We report on the fabrication, through photolithography techniques, and the
      detailed characterization, through direct transmission measurements, of a
      periodic system composed of five layers of photolithographically aligned
      micrometer-sized Ag split-ring resonators (SRRs). The measured transmission
      spectra for propagation perpendicular to the SRRs plane show a gap around 6 THz
      for one of the two possible polarizations of the incident electric field; this
      indicates the existence of a magnetic resonance, which is verified by detailed
      theoretical analysis. To our knowledge this is the first time that a system of
      more than one layer of micrometer-sized SRRs has been fabricated. The measured
      optical spectra of the Ag microstructure are in very good agreement with the
      corresponding theoretical calculations.

PMID- 15981530
TI  - Stroboscopic ultrahigh-resolution full-field optical coherence tomography.
AB  - We present a new technique that produces en face tomographic images with a 10
      micros acquisition time per image. The setup consists of an interference
      microscope with stroboscopic illumination provided by a xenon arc flash lamp (10
      micros flashes at 15 Hz). The tomographic images are obtained from two phase
      opposed interferometric images recorded simultaneously by two synchronized CCD
      cameras. Transverse resolution better than 1.0 microm is achieved by use of high
      numerical-aperture microscope objectives. The short coherence length of the
      source yields an axial resolution of 0.9 microm. 3 x 3 pixel binning leads to a
      detection sensitivity of 71 dB. Our system is suitable for various applications,
      particularly in biology for in vivo cellular-level imaging.

PMID- 15981531
TI  - Modulated imaging: quantitative analysis and tomography of turbid media in the
      spatial-frequency domain.
AB  - Experiments performed on turbid phantoms demonstrate that spatially modulated
      illumination facilitates quantitative wide-field optical property mapping and
      tomographic imaging in turbid media.

PMID- 15981532
TI  - Heterodyne detection of multiply scattered monochromatic light with a multipixel
      detector.
AB  - A new technique is presented for measuring the spectral broadening of light that
      has been multiply scattered from scatterers in motion. In our method the
      scattered light is detected by a heterodyne receiver that uses a CCD as a
      multipixel detector. We obtain the frequency spectrum of the scattered light by
      sweeping the heterodyne local oscillator frequency. Our detection scheme combines
      a high optical etendue (product of the surface by the detection solid angle) with
      an optimal detection of the scattered photons (shot noise). Using this technique,
      we measure, in vivo, the frequency spectrum of the light scattered through the
      breast of a female volunteer.

PMID- 15981533
TI  - Pulsed acousto-optic imaging in dynamic scattering media with heterodyne parallel
      speckle detection.
AB  - We present a new detection scheme for acousto-optic tomography based on pulsed
      wave ultrasound and illumination combined with heterodyne parallel speckle
      detection. This setup can perform tomographies inside several-centimeter-thick
      scattering samples. Test experiments confirm the suitability of this method for
      performing tomographies inside various types of optically scattering media,
      including liquids.

PMID- 15981534
TI  - Surface-sensitive polarized Raman spectroscopy of biological tissue.
AB  - In a two-layer diffusing medium, polarized light directly backscattering off the
      superficial layer will partially retain its sense of polarization, whereas deeper
      probing light will be increasingly depolarized by diffusion. This effect has been
      studied in both elastic scattering and fluorescence contexts. We apply this
      method to Raman scattering in two two-layer models with a highly diffusing lower
      layer of glucose powder and an upper layer of either clear plastic or chicken
      skin. We employ detection of orthogonal polarization states to generate a Raman
      spectrum of only the superficial layer by combining the orthogonal signals.

PMID- 15981535
TI  - Femtosecond time-resolved absorption processes in lithium niobate crystals.
AB  - Femtosecond pump pulses are strongly attenuated in lithium niobate owing to two
      photon absorption; the relevant nonlinear coefficient beta(p) ranges from
      approximately 3.5 cm/GW for lambda(p) = 388 nm to approximately 0.1 cm/GW for 514
      nm. In collinear pump-probe experiments the probe transmission at the double pump
      wavelength 2lambda(p) = 776 nm is controlled by two different processes: A direct
      absorption process involving pump and probe photons (beta (r) = 0.9 cm/GW) leads
      to a pronounced short-duration transmission dip, whereas the probe absorption by
      pump-excited charge carriers results in a long-duration plateau. Coherent pump
      probe interactions are of no importance. Hot-carrier relaxation occurs on the
      time scale of < or approximately equal to 0.1 ps.

PMID- 15981536
TI  - Direct four-photon excitation of amplified spontaneous emission in a nonlinear
      organic chromophore.
AB  - We report four-photon pumped amplified spontaneous emission in an organic
      chromophore. The phenomenon is observed when intense infrared laser radiation
      illuminates a nonlinear chromophore solution. As a result of this illumination, a
      strong and highly directional radiation in the visible wavelength range is
      generated in both the forward and the backward directions, with an angular
      divergence similar to that of the pump beam.

PMID- 15981537
TI  - Efficient generation of coherent blue light at 440 nm by intracavity-frequency
      tripling 1319-nm emission from a Nd:YAG laser.
AB  - A new route for efficiently generating coherent blue light has been explored
      based on intracavity effective third-harmonic generation in one partly
      periodically poled KTiOPO4 crystal placed inside the cavity of a diode-pumped
      Nd:YAG laser. To achieve efficient conversion, we use a dual-temperature oven to
      separately control the phase-matching conditions for the two second-order
      nonlinear processes. In addition, a Fabry-Perot cavity at 660 nm is incorporated
      into the crystal to increase the blue power significantly. When the laser is Q
      switched to produce long pulses, an average power of 118 mW is generated at 440
      nm at a pump power of 10 W.

PMID- 15981538
TI  - Temporally stable continuous-wave phase conjugation by stimulated Brillouin
      scattering in optical fiber with cavity feedback.
AB  - Temporally stable high-fidelity optical phase conjugation by stimulated Brillouin
      scattering of cw laser radiation is achieved in multimode silica fiber with
      cavity feedback. A power threshold of approximately 500 mW and a reflectivity of
      70% were obtained in a 340-m-long fiber with a cw Nd:YAG laser.

PMID- 15981539
TI  - Soliton dragging by dynamic optical lattices.
AB  - We report on the phenomenon of controllable soliton dragging by dynamic optical
      lattices induced by three imbalanced interfering plane waves. Because of such an
      imbalance, the transverse momentum of the lattice does not vanish, and thus the
      dynamic lattice can cause soliton dragging. The dragging rate is shown to depend
      on the amplitude and on the angle of incidence of the third plane wave making the
      optical lattice.

PMID- 15981540
TI  - Self-healing generation of spatial solitons in liquid crystals.
AB  - We demonstrate that, in suitably designed cells with undoped nematic liquid
      crystals, extraordinary-wave spatial solitons can be excited at every applied
      voltage without adjustments in the input polarization. Their walk-off, hence
      direction of propagation, is externally controlled over angles as large as 7
      degrees. The results pave the way not only to polarization-forgiving generation
      but also to voltage readdressing of these extraordinary-wave nematicons.

PMID- 15981541
TI  - Transition between different coherent light-matter interaction regimes analyzed
      by phase-resolved pulse propagation.
AB  - We present phase-resolved pulse propagation measurements that allow us to fully
      describe the transition between several light-matter interaction regimes. The
      complete range from linear excitation to the breakdown of the photonic bandgap on
      to self-induced transmission and self-phase modulation is studied on a high
      quality multiple-quantum-well Bragg structure. An improved fast-scanning cross
      correlation frequency-resolved optical gating setup is applied to retrieve the
      pulse phase with an excellent signal-to-noise ratio. Calculations using the
      semiconductor Maxwell-Bloch equations show qualitative agreement with the
      experimental findings.

PMID- 15981542
TI  - Surface-anchoring properties related to the distribution of polyimide chains in a
      twisted nematic liquid-crystal cell.
AB  - On the basis of a general Rapini and Papoular equation and the unified surface
      anchoring energy, surface-anchoring strength is newly defined theoretically as a
      function of the azimuthal deviation angle of the surface liquid-crystal directors
      and the statistical distribution of polyimide chains in a typical twisted nematic
      liquid-crystal cell. Then these are determined experimentally by the surface
      second-harmonic generation method, which is nonlinear optics, and the optical
      phase retardation method. We assume that the anisotropy distribution of polyimide
      chains induced by the rubbing strength is dominated by a Gaussian distribution
      around the rubbing direction.

PMID- 15981543
TI  - Polarization controllable spatial filter based on azo-dye-doped liquid-crystal
      film.
AB  - This investigation establishes the feasibility of exploiting the surface-assisted
      photoalignment effect in dye-doped liquid-crystal (DDLC) films as spatial filters
      with controllable polarization in optical signal processing. The fabrication
      relies on the fact that the various intensities of the diffracted orders are
      responsible for various changes of the polarization state induced by the
      photoaligned DDLC film. Specific spatial orders in Fourier optical signal
      processing can be filtered by use of an analyzer placed behind the sample to
      control the polarization state of the diffracted orders. A simulation was
      performed, and the results agree closely with the experimental data.

PMID- 15981544
TI  - Quantum emission dynamics from a single quantum dot in a planar photonic crystal
      nanocavity.
AB  - A theoretical quantum-optical study of the modified spontaneous emission dynamics
      from a single quantum dot in a photonic crystal nanocavity is presented. By use
      of a photon Green function technique, enhanced single-photon emission and
      pronounced vacuum Rabi flops are demonstrated, in qualitative agreement with
      recent experiments.

PMID- 15981545
TI  - Design of switches and beam splitters by use of chaotic cavities.
AB  - We propose the construction of electromagnetic (or electronic) switches and beam
      splitters by use of chaotic two-dimensional multiport waveguides. A prototype two
      port waveguide is locally deformed to produce a ternary incomplete horseshoe
      characteristic of mixed phase space (chaotic regions surrounding islands of
      stability where motion is regular). Owing to tunneling to the phase-space
      stability islands, quasi-bound states (QBS) appear. Then we attach transversal
      ports to the waveguide in the deformation region in positions where the phase
      space structure is only slightly perturbed. We show how QBS can be guided out of
      the waveguide through the attached transversal ports,giving rise to frequency
      selective switches and beam splitters.

PMID- 15981546
TI  - Manufacture of a 10-km-scale radius-of-curvature surface by use of a thin-film
      coating technique.
AB  - We tried a method of making a 10-km-class large-radius-of-curvature surface that
      would satisfy both low microroughness (0.1 nm rms) and low waviness (lambda/100)
      by forming a spherically curved film with a low-loss coating technique on a flat
      surface produced by mechanical (chemical) polishing. We obtained a SiO2 surface
      with a 10255 +/- 250-m radius of spherical curvature that had less than lambda/30
      waviness and 0.4-nm micro-roughness over a 9-cm-diameter area.

PMID- 15981547
TI  - Study of terahertz radiation generated by optical rectification on thin gold
      films.
AB  - Emission of terahertz (THz) radiation as a result of optical rectification of
      intense femtosecond laser pulses on thin gold films has been studied by time
      domain THz spectroscopy. The THz amplitude was measured as a function of film
      thickness and incidence angle. The experiments reveal that the emitted THz field
      is suppressed for a thickness below 100 nm, which gives evidence of the nonlocal
      character of the response. The variation of incidence angle allows us to estimate
      the components of susceptibility tensor chi2ijk. For thicker films and near
      grazing incidence, the emitted THz field attains a peak value of 4 kV/cm.

PMID- 15981548
TI  - Asynchronous optical sampling for high-speed characterization of integrated
      resonant terahertz sensors.
AB  - Two femtosecond Ti:sapphire lasers with slightly different repetition rates near
      1 GHz are coupled to implement high-speed asynchronous optical sampling. The
      application of this technique is successfully demonstrated in the field of
      terahertz time-domain spectroscopy (TDS). A time delay of 1 ns is scanned at a
      frequency of 5 kHz without moving mechanical parts. Compared with that of
      conventional TDS schemes based on lock-in detection and moving mirrors, the
      readout time of integrated resonant THz sensors is reduced by a factor of 20,
      opening the way for high-throughput THz sensing in marker-free DNA analysis.

PMID- 15981549
TI  - 100-attosecond timing jitter between two-color mode-locked lasers by active
      passive hybrid synchronization.
AB  - We have demonstrated a reduction of the timing jitter between passively
      synchronized Ti:sapphire and Cr:forsterite mode-locked lasers into a 100
      attosecond (as) regime by suppressing slow fluctuations with the use of active
      slow-bandwidth extracavity feedback. This active-passive hybrid synchronization
      scheme permits the achievement of timing jitters of 98 +/- 18 as at a bandwidth
      of 100 kHz and of 126 +/- 20 as at a bandwidth of 1 MHz for as long as 100 s.

PMID- 15981550
TI  - Targets for low-density lipoprotein cholesterol levels in patients with stable
      coronary heart disease: where are we now after the "treating to new targets"
      (TNT) trial?

PMID- 15981551
TI  - Recent advances in the treatment of pulmonary hypertension.

PMID- 15981552
TI  - Current trends in surgical reperfusion of the myocardium.

PMID- 15981553
TI  - The effect of shear stress on the onset and progression of atheromatous disease
      and on restenosis following transluminal therapies.

PMID- 15981554
TI  - Two-stent techniques for the treatment of coronary bifurcations with drug-eluting
      stents.

PMID- 15981556
TI  - Clinical use of Nebivolol in the treatment of chronic heart failure.

PMID- 15981555
TI  - Effects of Nebivolol on left ventricular function and exercise capacity in
      patients with non-ischaemic dilated cardiomyopathy. A randomised placebo
      controlled study.
AB  - INTRODUCTION: This study assessed the effects of Nebivolol on left ventricular
      (LV) function and exercise capacity in patients with non-ischaemic dilated
      cardiomyopathy (NIDC). METHODS: After enrolment in this double-blind trial, 60
      patients, aged 55 +/- 9.5 years, with angiographically proven NIDC, LV ejection
      fraction (EF) < 45%, NYHA class II-III, were randomised to either Nebivolol
      (target dose 5 mg) or placebo and were evaluated using echocardiography and
      exercise tests over 3 months. RESULTS: There were no baseline differences between
      the 2 groups regarding NYHA class, heart rate (HR), blood pressure (BP), LVEF or
      other echocardiographic variables. During follow-up, 4 patients in the Nebivolol
      and 5 in the placebo group discontinued treatment. After 3-months' treatment a
      significant decrease in NYHA class (p = 0.001), resting HR (p = 0.03), systolic
      and diastolic BP (both p < 0.001), left atrial diameter (p = 0.01) and LV end
      systolic volume (p = 0.046), and an increase in LVEF (p = 0.01) were observed in
      the Nebivolol group compared to placebo. The atrial contribution to total LV
      filling (p = 0.007) and the pulmonary venous (PV) systolic wave velocity (p =
      0.007) increased, whereas the atrial PV component decreased (p < 0.001) in the
      Nebivolol patients compared to placebo. Exercise duration decreased at 3 months
      (p = 0.01) compared to placebo, probably as a result of reduced maximal exercise
      HR (p < 0.001). CONCLUSIONS: Nebivolol is a safe and well-tolerated drug that
      improves NYHA class, systolic and diastolic LV function in NIDC patients,
      although it is associated with a lower maximal exercise duration at 3 months.

PMID- 15981558
TI  - Anaemia and heart failure: is its correction a therapeutic target? The role of
      erythropoietin.

PMID- 15981557
TI  - Economic evaluation of treatment strategies for patients suffering acute
      myocardial infarction in Greece.
AB  - INTRODUCTION: Acute myocardial infarction (AMI) is one of the leading causes of
      death in Greece and elsewhere. The objective of this paper was to conduct an
      economic evaluation of three alternative treatment options, alteplase, reteplase,
      and tenecteplase, in different groups of patients. METHODS: A systematic review
      of the literature was undertaken to identify studies evaluating the three
      treatments considered. Data from selected trials were extracted and applied to a
      decision analytic model, which has a time horizon extending to the end of a
      patient's life. The health outcomes included in the analysis contain all major
      health events that may occur after an AMI. Total treatment cost comprises the
      cost of initial treatment, the cost associated with hospitalisations due to AMI
      and events such as stroke, reinfarction, etc., and the lifetime costs of patients
      surviving. The model allows for different patient sub-groups. Simulation was used
      to test the robustness of the findings. RESULTS: For the baseline group, there
      was no major difference between the three treatments, in terms of treatment cost
      and survival. Specifically, lifetime cost per patient was around Euro 18,950
      (range Euro 18,947 - Euro 18,990) and overall survival was around 8.4 years
      (range 8.359 - 8.472). Nonetheless, for patients above the age of 75 and for
      patients starting treatment 4 hours after symptom onset, tenecteplase was more
      cost-effective compared to the other two treatments. Its incremental cost
      effectiveness ratio was Euro 2,205 in the former group and Euro 868 in the latter
      and these results reached high levels of significance. CONCLUSION: Despite its
      higher price, in the setting of the Greek National Health Service tenecteplase is
      a cost-effective treatment for AMI patients, comparable to alteplase and
      reteplase, and it should also be included in the positive drug list along with
      the other two drugs. Simple price comparison of alternative treatments is not the
      best option for supporting decisions on pricing and reimbursement of new
      therapies.

PMID- 15981560
TI  - The role of inflammatory agents in endothelial function and their contribution to
      atherosclerosis.

PMID- 15981559
TI  - Cholesterol levels and the benefit of statins in heart failure.

PMID- 15981561
TI  - Magnetic resonance imaging in the evaluation of Kawasaki disease.

PMID- 15981562
TI  - Severe thrombocytopenia after heparin therapy in a patient with unstable angina
      and recent stent implantation.
AB  - Heparin-induced thrombocytopenia represents a serious side effect of heparin
      therapy. Immune-mediated platelet activation results in thrombocytopenia,
      endothelial thrombin release and development of thrombosis, mainly venous. We
      report the case of a man with a history of coronary artery disease and recent
      stent implantation. This patient developed severe heparin-induced
      thrombocytopenia type II after low molecular weight heparin administration
      because of unstable angina which occurred two months after stent implantation.
      The patient was treated with a new anticoagulant regimen, fondaparinux sodium.
      There were no complications and platelet counts were restored to normal levels.

PMID- 15981563
TI  - The dawn of cardiology at the dawn of the 21st century: have we found the pathway
      to our heart?

PMID- 15981564
TI  - [Chromosomal rearrangements breakpoints clusterization: is the clonal selection
      involved].
AB  - Certain types of cancer are often correlate with certain chromosomal
      rearrangements. The chimaeric genes are formed as a result of this
      rearrangements, and the chimaeric proteins are the products of their expression.
      The breakpoints of such translocation are often clustered in the genome.
      Moreover, such breakpoint clusters often contain specific genomic elements like
      topoisomerase II consensus sites, nuclear matrix attachment regions and DNA
      sequences, which can make up secondary non-canonical structure. In this review we
      discuss whether breakpoints may be induced by chromatin structure. Furthermore,
      we bring up not touched upon literature question about the relation between the
      breakpoint clusters and the domain organization of corresponding proteins. We
      also consider possible mechanisms of chromosomal rearrangements.

PMID- 15981565
TI  - [New mechanism of retrogene formation in mammalian genomes: in vivo recombination
      during RNA reverse transcription].
AB  - L1 LINE retrotransposons play an important role in the shaping and permanent
      evolution of mammalian genomes. In particular, occupying about 20% of genomic
      DNA, they transduce their 3' flanking sequences to new genomic loci and create
      pseudogenes by reverse transcribing different kinds of cellular RNAs. Recently we
      discovered in mammalian genomes several families of chimeric pseudogenes,
      consisting of fused copies of various cellular transcripts. The characteristic
      peculiarities of such chimeric inserts suggest the involvement of L1 enzymatic
      machinery in their formation. The detailed sequence analysis revealed that 5'
      terminal parts of the chimeras are copies of nuclear RNAs, while 3' terminal
      sequences were formed on the templates of transcripts having cytoplasmic
      orientation. These data enabled us to propose the mechanism for the chimeras
      formation, comprising the switch of templates during RNA reverse transcription by
      L1 reverse transcriptase. The further identification of not only "double", but
      also "triple" chimeric retrogenes evidences the possibility of the double
      template switches as well. Some of the found chimeras are transcriptionally
      active, thus allowing to consider the discovered phenomenon as the new mechanism
      of the gene formation by "shuffling" of pre-existing transcribed sequences. Being
      active in mammals now, the mechanism appeared at least 75 million years ago and
      is evolutionary conserved.

PMID- 15981566
TI  - [Expression of the genes encoding RhtB family proteins depends on global
      regulator Lrp].
AB  - In the present work, further study of the genes encoding RhtB family proteins is
      presented. In our previous work the involvement of two family members, RhtB and
      RhtC, in efflux of amino acids was demonstrated. Now we investigated regulation
      of expression of the rhtB, rhtC, yeaS and yahN genes. It is shown that expression
      of these genes is under control of the global regulator Lrp, depends on the
      presence of some amino acids in growth medium, and increases during different
      physiological stresses.

PMID- 15981567
TI  - [Association study of the Ile50Val polymorphism of interleukin-4 receptor gene
      (IL4RA) with chronic viral hepatitis].
AB  - The study was performed to estimate association of the Ile50Val polymorphism in
      IL4RA and clinical characteristics of chronic viral hepatitis including course of
      disease manifestation which is determined by degree of hepatic fibrosis. The
      group under investigation included 61 patient diagnosed with chronic viral
      hepatitis. Control group consisted of 128 randomly selected inhabitants of Tomsk
      city. Genotyping of Ile50Val polymorphism in the groups was performed by RFLP
      (restriction fragment length polymorphism) analysis. There was no significant
      differences in genotypes and alleles frequencies between cases and controls.
      However differences in genotype distribution depend on fibrosis stage were
      detected. Ile/Val heterozygote frequency in subgroup of patients without hepatic
      fibrosis was lower (7.1%) than in controls (51.6%) (p = 0.002) due to increase of
      both homozygote classes. Subgroup of patients without hepatic fibrosis differed
      by genotype frequencies both from patients with moderate and severe disease stage
      (p = 0.035; p = 0.004).

PMID- 15981568
TI  - [Polymorphism of CTG-repeats in the DMPK gene in populations of Yakutia and
      central Asia].
AB  - Allele frequency distribution of CTG-repeat in the 3'-flanking region of DMPK
      gene was analyzed in populations of Yakutia (three ethnogeographical groups of
      Yakuts, Evenks, Evens, Yukaghirs, Dolgans) and Central Asia (Kazakhs, Uzbeks,
      Uighurs). Frequencies of CTG alleles were found to be significantly different in
      two regions. Allele frequency distribution in populations of Yakutia was similar
      to Asian populations, whereas Central Asian populations showed similarity to
      European populations. The features of allele spectrum in Yakut populations were
      discussed in terms of high prevalence of myotonic dystrophy in Yakuts. Our result
      supports the hypothesis of founder effect in spread of myotonic dystrophy in
      Yakuts. The phylogenetic relationships between the investigated populations based
      on polymorphism of CTG-locus of the DMPK gene have been analyzed as well.

PMID- 15981569
TI  - [Isolation of mitochondrial DNA binding proteins which are specific for maize
      cox1 promoter].
AB  - We purified DNA binding proteins which interact with the promoter region of cox1
      gene from maize mitochondria. Presence of poly[dIdC-dIdC] and KCl in
      concentrations up to 500 mM had no influence on binding efficiency demonstrating
      high specificity of complexes formed. Surprisingly, we did not detect DNA binding
      when probes containing promoter regions of other mitochondrial genes (cox3,
      rrn26) were used. Mobility shift competition studies also suggest that the
      protein posseses binding specificity towards cox1 promoter. The core motif AAGTA
      proved to be necessary for DNA binding. Using combination of EMSA and elution of
      proteins from PAG we showed that DNA-protein complex formed contains three
      polypeptides with molecular mass 60, 44 and 22 kD. We suggest that the isolated
      proteins may play an important role in the regulation of plant cox1 gene
      transcription.

PMID- 15981570
TI  - [Biochip development for polymorphism analysis in biotransformation system
      genes].
AB  - Large-scale population researches, diagnostics of genetic predisposition to
      multifactorial diseases, screening of the polymorphic loci associated with
      individual sensitivity to pharmaceutical preparations, require the development of
      effective, exact and rapid methods of analysis for detection of many mutations
      simultaneously. One of the most perspective methods to solve these problems is a
      method of allele-specific hybridization with biochips. Taking the analysis of
      mutations in genes CYP1A1, CYP2D6, GSTM1, GSTT1, NAT2, CYP2C9, CYP2C19 and MTHFR
      as an example we showed the efficiency of using the approach for identification
      of individual genetic polymorphism. We believe that the biochips can be also a
      convenient tool in pharmacogenetics researches.

PMID- 15981571
TI  - [Comparative molecular-genetic analysis of the beta-fructosidases in yeast
      Saccharomyces].
AB  - To infer the molecular evolution of polymeric beta-fructosidase SUC genes of the
      yeast Saccharomyces, we have cloned and sequenced a new SUC gene from S.
      cariocanus and determined the sequence similarity of beta-fructosidases within
      the genus Saccharomyces. The proteins of Saccharomyces cerevisiae and its five
      sibling species (S. bayanus, S. cariocanus, S. kudriavzevii, S. mikatae, S.
      paradoxus) have high degree of identity - 90-97%. The invertase of S. bayanus is
      the most divergent among the proteins studied. The data obtained indicated that
      the yeast invertases are highly conservative. In the coding regions of the SUC
      genes the pyrimidine transitions were the most abundant event due to silent
      changes mainly in the third codon position. There is only one, probably, non
      telomeric SUC gene in each of the Saccharomyces species. In S. cerevisiae, S.
      bayanus, S. kudriavzevii, S. mikatae and S. paradoxus the SUC gene have been
      mapped on chromosome IX, whereas in S. cariocanus this gene is located in
      chromosone XV, in the position of translocation.

PMID- 15981572
TI  - [Latent periodicity of serine-threonine and tyrosine protein kinases and another
      protein families].
AB  - We identified latent periodicity in catalytic domains of approximately 85% of
      serine/threonine and tyrosine protein kinases. Similar results were obtained for
      other 22 protein domains. We also designed the method of noise decomposition,
      which is aimed to distinguish between different periodicity types of the same
      period length. The method is to be used in conjunction with the cyclic profile
      alignment, and this combination is able to reveal structure-related or function
      related patterns of latent periodicity. Possible origins of the periodic
      structure of protein kinase active sites are discussed. Summarizing, we presume
      that latent periodicity is the common property of many catalytic protein domains.

PMID- 15981573
TI  - [Computational search for potential post-translational modification sites in
      human RNA polymerase III subunits].
AB  - The transcription of small stable non-translated RNA genes (class III genes),
      directed by RNA polymerase III, is strictly regulated in accordance to
      physiological state of the cell (growth rate, cell cycle stage, apoptosis, etc.)
      Post-translational modifications of the polymerase may play the important role in
      class III gene transcription regulation. Using computational programs searching
      for potential post-translational modifications sites in proteins (MotifScan,
      NetPhos 2.0, and Yin-Yan 1.2), possible sites of phosphorylation were identified
      in all 17 subunits of human RNA polymerase III, and possible sites of reciprocal
      phosphorylation and glycosilation ("yin-yan" sites) - in 13 subunits. Among the
      identified sites -17 sites of phosphorylation in seven subunits are conservative
      in human, Saccharomyces cerevisiae and Schizosaccharomyces pombe, including two
      "yin-yan" sites in two subunits. The data obtained can be used for experimental
      identification of RNA polymerase III modification sites in vivo in cells being in
      different physiological states.

PMID- 15981574
TI  - [p53 gene expression and activation of p53-dependent transcription in melanoma
      cell lines].
AB  - Malignant melanoma has poor prognosis because of its high metastatic potential
      and resistance to chemotherapy. A possible approach to more effective therapy is
      induction of p53-dependent apoptosis. This approach is promising, since the wild
      type p53 is expressed in most melanomas. An attempt was made to estimate the
      functional activity of p53 in several malignant melanoma cell lines. Most lines
      were characterized by a high protein level and nuclear localization of p53. All
      cell lines expressing the wild-type p53 showed stabilization of p53, its
      translocation into the nucleus, and activation of several target genes in
      response to DNA-damaging agents, suggesting that p53 was functionally active. A
      high-molecular-weight protein localized in the cytoplasm and mimicking a p53
      epitope was found in several cell lines. It was shown that the DO-1 epitope of
      this protein does not derive from p53, ruling out cytoplasmic retention of p53 in
      melanoma cell lines. A mechanism of camptothecin-induced stabilization of p53 by
      decreasing the level of the HDM2 mRNA was described for melanoma cells but not
      for normal melanocytes, which suggested a differential effect of camptothecin on
      tumor-derived and primary cells.

PMID- 15981575
TI  - [Induction of apoptosis of tumor cells by binase].
AB  - An induction of apoptosis by RNase from Bacillus intermedius (binase) and its
      mutants characterized with low catalytic activity (Lys26Ala and His101Glu) in
      human myelogenic erythroleukemia K562 cells, human lung carcinoma A549 cells and
      human peripheral blood mononuclear cells was studied. For the first time
      selective apoptogenic effects of binase toward leukemic blood cells was
      determined. Neither antiproliferative nor apoptotic effects of binase were
      detected in normal human peripheral blood mononuclear cells. Formation of low
      molecular weight oligonucleosomal DNA fragments (less than 50 Kb) which are an
      early marks of apoptosis was registered in solid tumor cells treated by binase.
      Using mutant RNases it was shown that decrease of catalytic activity to 2.5% of
      wild type enzyme activity leads to the loss of apoptogenic properties of enzyme.
      Selective apoptogenicity of binase found towards malignant cells confirmed that
      antitumor agents based on bacterial RNases could be considered as an alternative
      to standard chemotherapeutic drugs.

PMID- 15981576
TI  - [Caffeine sensitivity of the yeast Saccharomyces cerevisiae MCD4 mutant is
      related to alteration of calcium homeostasis and degradation of misfolded
      proteins].
AB  - The MCD4 gene of Saccharomyces cerevisiae encodes a protein involved in
      glycosylphosphatidylinositol (GPI) biosynthesis. However, some mutations in the
      MCD4 gene have pleiotropic effects that may not be related to the defects in GPI
      anchor synthesis. The ssu21 mutation in the MCD4 gene studied here causes
      sensitivity to caffeine. The screen for multicopy suppressors of caffeine
      sensitivity caused by the ssu21 mutation revealed genes involved in
      aminoglycerophospholipid metabolism, unfolded protein response, and protein
      degradation. The suppressor effect of all isolated genes was enhanced by an
      increase in concentration of external calcium, which is consistent with the
      ability of caffeine to block calcium entry into the yeast cell. Obtained results
      indicate that caffeine sensitivity caused by the ssu21 mutation could be due to
      cytoplasmic accumulation of misfolded proteins destined for degradation.

PMID- 15981577
TI  - [Interaction of HIV-1 reverse transcriptase with new minor groove ligands and
      their conjugates with oligonucleotides].
AB  - The influence of new non-natural regular minor groove binders (MGB), containing 2
      4 imidazole, pyrrole or thiazole residues, and their conjugates with
      oligonucleotides, on the polymerization reaction catalyzed by HIV-1 reverse
      transcriptase was analyzed. Various model template-primer complexes: poly(A)
      oligo(U), poly(A)-oligo(dT), poly(dA)-oligo(U), poly(dA)-oligo(dT) and activated
      DNA were used. The concentration of oligopeptides, giving 50% inhibition (I50) of
      the RT-dependent polymerization reaction, was shown to depend strongly on the
      structure of template-primer complexes, number and type of the heterocycle rings
      in the MGBs analyzed. The range of I50 for the most of the compounds studied is
      7.7 x 10(-3)-1.0 x 10(-5) M. The affinity of MGB is minimal for poly(A)-oligo(U).
      However, some of imidazole and pyrrole-containing MGBs demonstrated unusually
      high affinity (I50 = 3 x 10(-9)-4 x 10(-8) M) to the above template-primer in
      complex with RT. The affinity of conjugates of thiazolecarboxamides with
      oligonucleotides complementary or partially complementary to the template, is 1-4
      orders higher compared to free thiazolecarboxamides. The possible reasons of the
      dependence of I50 values upon the structure of the template-primer complexes, the
      structure of MGB, and their conjugates with oligonucleotides are discussed.

PMID- 15981578
TI  - [Computer analysis of conformational and physicochemical percularities of
      sequences cleaved by DNA topoisomerase I].
AB  - After complexation of DNA with enzymes a specific adaptation of DNA structure
      including its partial or nearly complet melting, change of sugar-phosphate
      backbone structure, stretching, compression, bending or kinking, flipping out of
      nucleotides from the DNA helix, etc. take place. The full set of such changes is
      specific for each individual enzyme and is a very important for effective
      adjustment of reacting orbitals of enzyme and specific DNA atoms with accuracy up
      to 10-15 degrees. Efficiency of DNA sequence adaptation in the direction
      providing by enzyme depends on many specific structural characteristics of DNA.
      Maximal adjustment of DNA structure can be achieved only for specific sequences,
      therefore on going from nonspecific to specific DNAs the increase of the
      catalytic rate by 4-8 orders of magnitude takes place. DNA topoisomerase I is a
      sequence-dependent enzyme, but it can cleave with lower efficiency DNA sequences,
      which are significantly different from an optimal one. We have carried out the
      computer analysis of structural characteristics of many DNA sequences utilizing
      by topoisomerase using the method which is based on the analysis of
      conformational and physico-chemical characteristics of DNA helix and gives a
      detailed information about similarities or differences of DNA structural units.
      In addition to such characteristics as base tilt angle, shift of base pair, helix
      steering angle, and helix step for all cleaved sequences the presence of
      sterically disadvantageous contacts in small grove between N3 and NH2 of guanines
      and N3 of adenines were detected which corresponds to the presence Py-Pu
      dinucleotides in the cleavaged site. In addition, for optimal sequences bending
      of DNA helix toward major groove is characterized. The proposed method seems to
      be a very perspective for the analysis of an efficiency of nucleic acids cleavage
      by different DNA- and RNA-dependent enzymes.

PMID- 15981579
TI  - [Carbonic anhydrase B interactions with water and urea].
AB  - Carbonic anhydrase B unfolding with urea (pH 5.7, T = 298 K) was studied by high
      resolution NMR spectroscopy. The effectiveness of spin-diffusion influencing
      compactness of the protein molecule can be described with the rigidity parameter
      G. Parameter G displays sigma-like characteristic behavior when concentration
      increases. The ratio between integral intensities of urea and protein signals in
      spin-diffusion and normal 1D spectra are the same. This suggests that there is no
      predominant urea-protein molecular interaction. The concentration of large
      protein-solvent associates increases rapidly at urea levels of 4.2-6.2 M implying
      that protein molecule shifts to a molten globule state. Protein-solvent
      associates are dissipating with urea concentration increase to above 6.6 M when
      carbonic anhydrase B polypeptide chain is completely unfolded.

PMID- 15981580
TI  - [Comparison of adjuvant activities of glucosaminyl-muramyl dipeptide and of the
      gene coding for granulocyte-macrophage colony-stimulating factor in DNA
      immunization against herpes simplex virus].
AB  - Adjuvant activities of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      and synthetic glucosaminyl-muramyl dipeptide (GMDP) were studied in immunization
      against type 1 herpes simplex virus (HSV1). Gene encoding the gD HSV1 protein
      (pDNAgD) was used as an immunogen. Gene encoding GM-CSF in pDNAGM-CSF plasmid,
      which was developed for eukaryotic expression, and GM-DP were used as immune
      response modulators. GMDP and plasmid DNA with inserted GM-CSF gene enhanced T
      cell immune response to HSV1 after a single injection (pDNAGM-CSF) or 24 h before
      (GMDP) immunization with the gD HSV1 gene. Both adjuvants increased protective
      effect of DNA-immunization by a virus gene with 63 up to 100% after injection of
      two genes and up to 96% after the viral gene was inoculated 24 h after GMDP.
      These high effects indicate that further investigation of anti-HSV1 DNA-based
      vaccines used with genetic and peptide adjuvant is prospective.

PMID- 15981581
TI  - [Human milk lactoferrin hydrolyzes nucleoside-5'-triphosphates].
AB  - Lactoferrin (LF) is a main iron-transfering glycoprotein of human barrier body
      fluids, blood and milk. LF, a protein of the acute phase, is responsible for
      nonspecific cells defense against microbial and viral infection and cancer
      diseases. LF is an important component of the passive immunity of newborns
      system. LF, an extremely polyfunctional protein, is the object of intensive
      investigations. In this work electrophoretically homogeneous LF from human milk
      was prepared. Affinity chromatography of LF on Blue Sepharose separated the
      protein into several distinct isoforms with different affinities to this resin.
      Two of this isoforms possess nucleoside-5'-triphosphate-hydrolyzing activity.
      Using several methods including in-gel ATPase activity assays, we show that ATP
      (and others NTP) hydrolysis is an intrinsic property of LF, and that LF is the
      major ATPase of human milk. It was shown that ATP-hydrolyzing site is located in
      C-lobe of LF.

PMID- 15981582
TI  - Translation and cross-cultural adaptation of assessment instruments used in
      psychological research with children and families.
AB  - With the increased globalization of psychology and related fields, having
      reliable and valid measures that can be used in a number of languages and
      cultures is critical. Few guidelines or standards have been established in
      psychology for the translation and cultural adaptation of instruments. Usually
      little is reported in research publications about the translation and adaptation
      process thus making it difficult for journal readers and reviewers to adequately
      evaluate the equivalency and quality of an instrument. In this study, issues
      related to the translation and adaptation of assessment instruments for use in
      other cultures and/or languages are addressed. Existing literature on translation
      is reviewed and examples from the clinical child and family psychology field are
      given to illustrate relevant issues. Suggestions are made for avoiding common
      translation errors.

PMID- 15981583
TI  - A dogma in need of a reformation.

PMID- 15981584
TI  - Immunolocalization of the proton-coupled oligopeptide transporter PEPT2 in
      developing rat brain.
AB  - This study examined the tissue distribution, cellular localization, and
      developmental expression of the PEPT2 protein in rat brain. Immunoblot and
      immunocytochemistry analyses were performed with specific rat PEPT1 and PEPT2
      antisera developed in our laboratory. Rats were examined from fetus (gestation
      for 17 days) to adult (day 75). On immunoblot analysis, the PEPT2 protein was
      detected in cerebral cortex, olfactory bulb, basal ganglia, cerebellum, and
      hindbrain sections of adult brain, with the strongest signals in cerebral cortex.
      No PEPT1 protein was found in brain. Expression levels of the PEPT2 protein in
      cerebral cortex were maximal in the fetus and declined rapidly with advancing
      age. Adult protein levels were approximately 14% of that observed in fetus. In
      immunofluorescence experiments, the strongest PEPT2 signals were observed in
      epithelial cells of the choroid plexus for both adult and neonate brains. The
      PEPT2 protein was exclusively expressed on the apical membrane (CSF-facing) of
      choroid plexus epithelia. In double labeling experiments, PEPT2 immunoreactivity
      in adult brain colocalized with NeuN, a neuronal marker, but not with GFAP, an
      astrocyte marker. In contrast, in neonatal brain, PEPT2 immunoreactivity
      colocalized with both GFAP and NeuN. These findings demonstrate that the PEPT2
      protein is found throughout the brain. The apical expression of PEPT2 in choroid
      plexus suggests that it is involved in the export of neuropeptides, peptide
      fragments, and peptide-like drugs from cerebrospinal fluid. PEPT2 may also play a
      role in the regulation of neuropeptide concentrations in extracellular fluid,
      especially during early development.

PMID- 15981585
TI  - A novel rhodamine-riboflavin conjugate probe exhibits distinct fluorescence
      resonance energy transfer that enables riboflavin trafficking and subcellular
      localization studies.
AB  - Riboflavin (vitamin B2, RF) is taken up in eukaryotic cells via specialized
      transport mechanisms. Although RF has fluorescence properties, direct microscopic
      visualization of RF uptake and trafficking has been complicated by cellular
      autofluorescence. We describe the synthesis, cellular uptake characteristics, and
      spectroscopic properties of a novel rhodamine-riboflavin conjugate (RD-RF),
      including absorption and emission spectra, two-photon excitation spectra, and
      fluorescence pH dependence. The conjugate has a molar extinction coefficient of
      23 670 M(-1) cm(-1) at 545 nm (excitation wavelength) with a fluorescence quantum
      yield of 0.94. This compound exhibits intramolecular fluorescence resonance
      energy transfer (FRET). Selective quenching of the FRET signal is observed when
      RD-RF is bound with high affinity by the chicken riboflavin carrier protein. In
      addition to the typical rhodamine excitation and emission, FRET provides a
      secondary signal for conjugate localization and an in situ mechanism for
      observing riboflavin binding. Solution and in vitro stability determinations
      indicate that the linkage between riboflavin and rhodamine is stable for the
      duration of typical pulse--chase and cellular trafficking experiments. The
      distinct spectroscopic properties of RD-RF together with a comparable affinity
      for RF-binding proteins render it an excellent tool for the study of RF transport
      and trafficking in living cells.

PMID- 15981586
TI  - Exploratory chemoinformatic analysis of cell type-selective anticancer drug
      targeting.
AB  - In pharmaceutical development, structure-activity relationship studies aim to
      identify characteristics of chemical structures associated with well-defined
      activity end points. While this goal-driven approach is ideally suited for lead
      development purposes, a more exploration-driven approach is needed to discover
      cell type-selective drug targeting mechanisms in complex data sets. Growth
      inhibition profiles across different cancer cell lines are potentially
      informative with respect to molecular mechanisms targeting the activity of
      anticancer agents to specific tumor cells, yet only a small number of mechanistic
      associations between chemical structure and growth inhibition profiles have been
      discovered to date. Here, we have applied an exhaustive statistical analysis
      strategy to more than 10000 compounds in the NCI's anticancer agent database to
      identify molecular substructures associated with specific cytotoxicity signatures
      against a panel of human tumor-derived cancer cell lines (the Developmental
      Therapeutics Program 60-cell line panel). Some of the most significant
      substructures conferring cell type-selective cytotoxic activity include a large
      family of delocalized lipophilic cations; chloropurines, chloropyrimidines, and
      thiazoles; organosulfur chelators and organometallic complexes; and an
      unexpectedly related family of alkyl-lysophospholipids and phosphate prodrugs.
      Information from cell-based assays and gene expression measurements have been
      related to substructures represented in the chemical space covered by the
      library, yielding several candidate targeting mechanisms.

PMID- 15981587
TI  - Regulation of drug transporters by the farnesoid X receptor in mice.
AB  - The farnesoid X receptor (FXR, NR1H4) regulates bile acid and lipid homeostasis
      by acting as an intracellular bile acid-sensing transcription factor, resulting
      in altered expression of enzymes and transporters involved in bile acid synthesis
      and transport. Here, we quantitatively analyzed the alterations in expression
      levels of drug transporters, mainly organic anion-transporting polypeptides
      (oatp), in wild-type and FXR-null mice to evaluate the role of FXR in their
      expression and regulation by cholic acid. Changes in the mRNA amounts in liver,
      kidney, small intestine, and testis in FXR-null mice fed with or without a
      supplement of 0.5% cholic acid in the diet were analyzed by semiquantitative RT
      PCR. In FXR-null mice, the mRNA levels of oatp1, oatp2, oatp3, and octn1 were
      lower than those of wild-type mice in kidney and testis, while there was no
      difference in liver or small intestine. Cholic acid feeding led to significantly
      decreased levels of expression of oatp1 and oct1 and an increased level of
      expression of oatp2 in wild-type mouse liver. In FXR-null mice, oatp1 and other
      transporters were downregulated in liver, kidney, and testis, whereas small
      intestine ASBT, octn2, and pept1 were upregulated. Our results suggested that FXR
      is involved in the transcriptional regulation of oatp and other transporters in a
      tissue-specific manner. Furthermore, the effect of cholic acid treatment
      indicates the involvement of regulatory mechanism(s) other than FXR.

PMID- 15981588
TI  - Circumventing P-glycoprotein-mediated cellular efflux of quinidine by prodrug
      derivatization.
AB  - The objective of this study is to investigate whether transporter-targeted
      prodrug derivatization of quinidine, a model P-glycoprotein (P-gp) substrate, can
      circumvent P-gp-mediated efflux. The L-valine ester of quinidine (val-quinidine)
      was synthesized in our laboratory. Uptake and transport studies were carried out
      using the MDCKII-MDRI cell line at 37 degrees C for 10 min and 3 h, respectively.
      [3H]Ritonavir and cyclosporine were also used as model P-gp substrates to
      delineate the kinetics of translocation of val-quinidine across the MDCKII-MDRI
      cell monolayer. The rate of uptake of [3H]ritonavir by MDCKII-MDRI cells
      exhibited a 2-fold increase in the presence of 75 microM quinidine, but 75 microM
      val-quinidine did not demonstrate any effect on [3H]ritonavir uptake. The rate of
      transport of quinidine from the basolateral to the apical membrane [(18.3 +/-
      1.25) x 10(-6) cm s(-1)] and from the apical to the basolateral membrane [(6.5 +/
      0.66) x 10(-6) cm s(-1)] exhibited a 3-fold difference. However, transport of
      val-quinidine from the apical to the basolateral membrane [(5.13 +/- 0.49) x 10(
      6) cm s(-1)] and from the basolateral to the apical membrane [(6.17 +/- 1.28) x
      10(-6) cm s(-1)] did not demonstrate any statistically significant difference.
      Moreover, cyclosporine, a potent P-gp substrate and/or inhibitor, did not alter
      the transport kinetics of val-quinidine. The rates of uptake of [3H]Gly-Sar and
      various amino acid model substrates were reduced in the presence of 200 microM
      val-quinidine. Results from this study clearly indicate that prodrug
      derivatization of quinidine into val-quinidine can overcome P-gp-mediated efflux.
      Val-quinidine once bound to a peptide or amino acid transporter is probably not
      recognized and cannot be accessed by the P-gp efflux pump. Transporter-targeted
      prodrug derivatization seems to be a viable strategy for overcoming P-gp-mediated
      efflux.

PMID- 15981589
TI  - Effect of diabetes mellitus and insulin on the regulation of the PepT 1 symporter
      in rat jejunum.
AB  - This investigation focused on studying the effects of insulin-dependent diabetes
      mellitus and insulin treatment on absorption of glycylsarcosine (Gly-Sar) across
      the Sprague-Dawley rat jejunum, using in situ perfusion in a physiologic acidic
      microenvironment at pH 6.0. Rats were divided into five groups: normal controls
      in group I, normal colchicine-treated rats in group II, normal cytochalasin
      treated rats in group III, streptozotocin-induced diabetic rats in group IV, and
      insulin-treated diabetic rats in group V. Histologic studies of the five
      different groups showed morphologic changes upon induction of diabetes and
      treatments with colchicine and cytochalasin and several variations in post-1
      month diabetic rats treated with insulin. The rate of uptake of Gly-Sar was
      significantly reduced in the diabetic state. The comparison of colchicine-treated
      and cytochalasin-treated rats to the diabetic group suggests that an intact
      cytoskeleton and tight junctions may play a role in jejunal dipeptide absorption.
      In the diabetic and insulin-treated group, the dipeptide influx rate was
      significantly increased compared to that of the nontreated controls. The
      regulation of the PepT 1 symporter was further assessed by immunostaining and
      Western blot analyses in the normal, diabetic, and diabetic and insulin-treated
      groups. Our results showed that a downregulation of PepT 1 in the diabetics
      seemed to be due in part to the low systemic insulin levels, and not necessarily
      to hyperglycemia. In addition, the results suggest a probable role of systemic
      insulin binding at the vascular site of the jejunal epithelium, and the role that
      this hormone may be playing in the regulation and probably cellular trafficking
      of PepT1.

PMID- 15981590
TI  - Assessment of a modular transfection system based upon cellular localization of
      DNA.
AB  - Delivery of plasmid DNA for protein production in mammalian cells is not an
      efficient process. In this study, the theory that cellular localization of
      plasmid DNA increases transfection efficiency is examined with an emphasis on the
      understanding of the cellular association of the components of a ternary
      transfection complex. Mammalian cells take up transfection reagent-DNA complexes
      primarily from their local environment. Via formation of a ternary complex
      consisting of the DNA-transfection reagent complex and a heavy particle, such as
      silica, the efficiency of transfection is substantially increased. We have
      analyzed cells transfected with the ternary complexes to determine if
      sedimentation alone affects the percentage of cells that contain the complexes or
      specific components of the complex. A significant fraction of cells associate
      with the ternary complexes, including silica nanoparticles. The percentage of
      cells that associate with DNA was not significantly influenced by the use of the
      ternary complex. This result suggests that the silica nanoparticles are more than
      just a sedimentation agent, being also a secondary transfection reagent. These
      data also confirm that cells may contain transfection reagent-DNA complex but do
      not express the protein of interest. This knowledge will be used in further
      research to better design transfection reagents that will increase the efficiency
      of protein production.

PMID- 15981591
TI  - Ultrasound-enhanced tumor targeting of polymeric micellar drug carriers.
AB  - Cancer chemotherapy is often complicated by toxic side effects of anticancer
      drugs. We are developing a new modality of tumor chemotherapy aimed at
      circumventing side effects of treatment via drug targeting to tumors. The
      technique is based on drug encapsulation in polymeric micelles followed by a
      controlled drug release at a target site triggered by ultrasonic irradiation. The
      encouraging in vitro results of previous years warranted animal experiments for
      verification of the in vivo feasibility of the proposed technique. We report here
      on the effect of ultrasound on a biodistribution of a micellar drug carrier
      (fluorescently labeled Pluronic micelles) in ovarian cancer-bearing nu/nu mice.
      The degree of carrier accumulation in the cells of various organs was
      characterized by flow cytometry. Polymeric micelles were formed in either pure
      Pluronic P-105 solutions (unstabilized micelles) or 1:1 (weight) mixtures of
      Pluronic P-105 with PEG-diacylphospholipid (stabilized micelles). Intraperitoneal
      (ip) and intravenous (iv) injections were compared. The data showed that a 30 s
      ultrasonic irradiation by 1 or 3 MHz ultrasound applied locally to the tumor
      significantly enhanced accumulation of Pluronic in the tumor cells, which was
      observed for both ip and iv injections and for unstabilized and stabilized
      micelles. The data indicated targeting of Pluronic micelles to the tumors; the
      degree of targeting was enhanced by a local tumor sonication.

PMID- 15981592
TI  - FTIR spectroscopic imaging of dissolution of a solid dispersion of nifedipine in
      poly(ethylene glycol).
AB  - FTIR imaging was applied to study solid dispersions of a poorly water-soluble
      drug in poly(ethylene glycol) (PEG) and dissolution in water. It has been shown
      that initially amorphous nifedipine crystallizes within PEG-8000 for formulations
      with a drug loading of at least 10 wt%. The formation of a significant amount of
      crystalline drug within the polymer matrix reduces the rate of dissolution of the
      drug. This FTIR spectroscopic imaging in the ATR mode provides novel insight into
      the mechanism of dissolution of nifedipine from solid dispersions in water
      soluble polymers, which is valuable in optimization of manufacturing these
      formulations.

PMID- 15981593
TI  - [Knowledge gaps are dangerous. Safe general practice: 2nd Cologne symposium on
      the topic of nursing rights].

PMID- 15981594
TI  - [Tuberculosis: on the upswing again?].

PMID- 15981595
TI  - [Integration of family with Islamic beliefs: understanding as the path to
      empathy].

PMID- 15981596
TI  - [Nurse in the prison hospital: 2 roles for 1 person].

PMID- 15981597
TI  - [Nursing in the drug rehabilitation center. "Progress in small steps" (interview
      by Hanna Lucassen)].

PMID- 15981598
TI  - [Pregnant drug addicts. The risk of great hopes].

PMID- 15981599
TI  - [Unemployment and health: defective management--sick personnel].

PMID- 15981600
TI  - [Health of illegal immigrants: no asylum--no nursing care?].

PMID- 15981601
TI  - [Special support for expectant parents in Hungary: responsibility needs to be
      learned].

PMID- 15981603
TI  - [Presentation of statistical data in nursing 7--2 concepts and their
      limitations].

PMID- 15981602
TI  - [Evidence-based nursing care for patients with feeding tubes--2: Preventing
      complications].

PMID- 15981604
TI  - [Group homes for patients with dementia: stress is compensated by motivation].

PMID- 15981605
TI  - [Training of new coworkers: the guardian principle].

PMID- 15981606
TI  - [Obligations of nursing insurance: the threat of domestic deterioration does not
      call for intervention].

PMID- 15981607
TI  - [HIV and AIDS in the Ukraine: management of patients is a catastrophic].

PMID- 15981608
TI  - [General practice interventions by a Finnish nursing school: voices of the
      wilderness in South Africa].

PMID- 15981609
TI  - [Spiritual dimensions of nursing--1: The ways of Hinduism].

PMID- 15981610
TI  - [(Not) an illness like any other].

PMID- 15981611
TI  - [Basic academic education in Berlin: Bachelor of Nursing].

PMID- 15981612
TI  - ["Carnival of Cultures": influence of increasing numbers of patients with
      immigration background on nursing competence].

PMID- 15981613
TI  - Providing a secure base: parenting children in long-term foster family care.
AB  - This paper reports on a longitudinal study of children growing up in long-term
      foster family care. It focuses attention on the challenges for foster carers in
      providing a secure base for foster children in middle childhood and early
      adolescence, who have come predominantly from backgrounds of abuse, neglect, and
      psychosocial adversity. Separation and loss in the children's lives, often
      through multiple placements, increase the likelihood of difficulties across a
      range of development. These children tend to be wary, distrustful, and
      controlling when they enter foster placements, but need from their carers many of
      the caregiving qualities most commonly described as providing a secure base in
      infancy. This study describes a model of parenting which uses four caregiving
      dimensions that are consistent with attachment theory and research: promoting
      trust in availability, promoting reflective function, promoting self-esteem, and
      promoting autonomy. A fifth dimension, promoting family membership, is added, as
      it reflects the need for children in long-term foster family care to experience
      the security that comes from a sense of identity and belonging. Qualitative data
      from the study demonstrates the usefulness of this model as a framework for
      analysis, but also suggests the potential use of such a framework for working
      with and supporting foster carers.

PMID- 15981614
TI  - Challenges of foster care.

PMID- 15981615
TI  - Anna's story: a qualitative analysis of an at-risk mother's experience in an
      attachment-based foster care program.
AB  - This study chronicles an at-risk mother's experience in an alternative foster
      care program. Influenced by attachment theory, the Children's Ark reunited
      children with their mothers in a supervised home environment while also providing
      residential support, intensive therapy, and education. After losing custody of
      her infant Kindra, 18-year-old Anna participated in the Ark for 2 years, after
      which she regained custody of Kindra. We assessed Anna and Kindra at multiple
      times using a variety of instruments, including a semi-structured interview, the
      Adult Attachment Interview, and the Strange Situation procedure. Anna moved from
      a profoundly insecure state of mind to a secure one, while Kindra moved from a
      resistant to a secure attachment. Qualitative analyses of Anna's interviews
      documented growth in her capacity to use the important relationships at the Ark
      as secure bases and to welcome rather than fear intimacy with Kindra. The
      qualitative analyses also described growth in Anna's capacities for reflective
      functioning and positive changes in her internal working model. We conclude with
      an analysis of the process of change from the perspective of attachment theory.

PMID- 15981616
TI  - Attachment state of mind and perceptual processing of emotional stimuli.
AB  - This study aimed to investigate the relationship between attachment state of mind
      and perceptual processing of social and non-social, affective, and neutral
      material. A total of 57 young adults completed the Adult Attachment Interview
      (AAI) plus an experimental task in which their perceptual thresholds to different
      types of pictures were assessed. Significant correlations were found between the
      AAI dimensions and perceptual thresholds for social stimuli such as social
      interactions or human faces displaying emotional expressions. As expected, no
      relationships were found between the AAI and perception of neutral stimuli. The
      pattern of correlations was especially clear for the dismissing dimension. The
      results suggest that higher vigilance to social stimuli is related to dismissing
      attachment tendencies and, to a milder degree, to preoccupied tendencies.

PMID- 15981617
TI  - [Investigation on the therapeutic effect of carbamazepine on the mood disorders
      in Japan].
AB  - A history of investigation on the mood stabilizing effect of carbamazepine in
      Japan was described. Following the initial open trials in the early 1970s in
      which the antimanic and prophylactic effects of carbamazepine were demonstrated
      on a large number of patients for the first time in the world, the mood
      stabilizing effect was confirmed by our double-blind study comparing
      carbamazepine vs chlorpromazine in the late 1970s and that comparing
      carbamazepine and lithium in late 1980s which were performed with multi
      institutional cooperation in Japan. The studies on carbamazepine in the early
      1970s in Japan stimulated the study on the mood stabilizing effect of
      antiepileptic drugs in the world and contributed to the establishment of the
      criteria "mood-stabilizers". The similarities and differences of responders for
      carbamazepine and lithium and effect of combination therapy of carbamazepine and
      lithium were also studied by our research group in Tottori University.

PMID- 15981618
TI  - [A clinical trial for developing PICU management scale, a tool reviewing the
      frequency and use of seclusion and restraint in psychiatric acute care].
AB  - OBJECTIVE AND METHODS: Medical management in psychiatric acute care involving
      seclusion and restraint is an intervention of which reasonable use is often
      required. Regarding such measures, guidelines for seclusion and restraint are
      important, and also, psychiatric treatment facilities should engage in a
      continuous quality improvement process that seeks to minimize the use of
      seclusion and restraint. To review and monitor the existing use of seclusion and
      restraint, the authors developed a tool, the "PICU management scale", and
      investigated its usefulness in two functionally different psychiatric wards, a
      psychiatric emergency care unit (emergency ward) and a psychiatric acute care
      unit (acute ward) in the Japanese payment system. The PICU management scale is a
      tool which classifies the status of psychiatric intensive care into six
      categories by four factors; "S: seclusion", "R: restraint", "N: forced nutrition"
      and "Ph: physical care", and we evaluated its usefulness by occurrence of
      variance. In terms of minimizing or optimizing the use of seclusion and
      restraint, we also analyzed characteristics and risk factors of 1) recurrent
      application of seclusion and restraint, 2) high PICU management ranking, and 3)
      prolongation. RESULTS: During the five months of investigation, medical
      management involving seclusion and restraint was applied in 98 cases at the
      emergency ward and 50 at the acute ward. The total number of management days was
      894 and 950, respectively. The mean management duration per case was 9.1 and 19.0
      days, respectively. The variance was 2.5 % and 4.5 %, respectively, and our tool
      covered most of the statuses and conditions observed in psychiatric emergency and
      acute care. Analysis of the variance suggested the existence of a trend which is
      considered to be typical of the status of medical management. Most cases that
      required recurrent application of seclusion and restraint were diagnosed as F0 or
      F2 in ICD -10, and hebephrenic cases with a high grade of disability, refractory
      paranoid schizophrenic, or drug-resistant cases in F2 were remarkable in this
      category. In the high PICU management ranking, most cases were related to
      consciousness disturbance, and the mean duration of intervention was short.
      Reversal of the therapeutic stage was considered to be a risk factor of
      prolongation. CONCLUSION: The "PICU management scale" is considered to be a
      useful tool for minimizing the use of seclusion and restraint, in addition to the
      guidelines for the use of seclusion and restraint. Contributions to team strategy
      and consensus by the addition of objectivity or symbolizing are also expected. To
      verify these findings and make further progress, more clinical trials using this
      tool in various institutions are required.

PMID- 15981620
TI  - [Psychotherapy, from human environment].
AB  - Therapy for Schizophrenia has two stages; it is built on medical model during
      acute phase, and social support model during recovering phase. We are required to
      pay attention to both approaches, and we also need what millieu therapy has once
      excluded from care. Psychotherapy for Schizophrenia is defined as "respects, such
      as reliability during acute phase and care for maintenance of social
      functioning."

PMID- 15981619
TI  - [A questionnaire survey on judgment of criminal responsibility].
AB  - The authors conducted questionnaire surveys utilizing model cases with the aim of
      investigating the current views of psychiatrists regarding criminal
      responsibility judgments in forensic psychiatric evaluations. Six model cases
      injury by a person with acute schizophrenia, indecent assault by a person with
      chronic schizophrenia, attempted murder by a woman with depression, arson by an
      alcohol abuser, burglary by an amphetamine abuser, rape and indecent assault by a
      person with personality disorder-were presented to 345 psychiatrists, who were
      asked about criminal responsibility and appropriate treatment for each of the
      cases. One hundred eighty-five of the psychiatrists responded. In the case of
      acute schizophrenia with hallucination and delusion, the case of severe
      depression, and the personality disorder case, there was a high level of
      agreement between the evaluations of criminal responsibility made by the
      different respondents, but in the case of chronic schizophrenia, the case of
      alcohol-induced psychotic disorder, and the case of amphetamine abuse, there were
      variations in the evaluation of criminal responsibility, with many respondents
      emphasizing the patient's symptoms and condition at the time of the offense, and
      relatively few emphasizing whether the disorder was endogenous. Regarding the
      form of treatment, many of the respondents recommended compulsory hospitalization
      for the case of acute schizophrenia with hallucination and delusion, while at the
      same time recommending treatment in a prison environment for the personality
      disorder case. In contrast, for the case of chronic schizophrenia and the case of
      alcohol-induced psychotic disorder, opinion was divided as to whether the subject
      should be handled with a medical or a judicial approach. Regarding treatment for
      the case of alcohol-induced psychotic disorder and the case of amphetamine abuse,
      there was a tendency to make a judgment based on the subject's condition at the
      point of psychiatric evaluation, which was not necessarily linked to the criminal
      responsibility.

PMID- 15981621
TI  - [Early childhood trauma and stress-related psychiatric disorders: neuroscience
      perspective].
AB  - Morphometric studies using magnetic resonance imaging have reported smaller than
      normal volumes of the hippocampus in stress-related psychiatric disorders such as
      major depression, post-traumatic stress disorders (PTSD) etc... On the other
      hand, epidemiological studies have suggested that early childhood trauma
      including child abuse and sexual abuse is associated with markedly elevated rates
      of major depression and PTSD. Psychoanalysist and child psychiatrists have
      reported that mother-child relationship and fostering environment in early
      childhood strongly affect the later mental development and increase the
      prevalence rate of various psychiatric disorders, but its biological mechanism
      has not been elucidated. Recent progress of neuroscience research has brought a
      possibility to elucidate molecular biological mechanism of this developmental
      psychological issue. The author reviews recent neuroscience researches focused on
      the effect of early childhood trauma on the stress vulnerability and the
      pathogenesis of stress-related psychiatric disorders.

PMID- 15981622
TI  - [Clinical and virologic characteristics and treatment for chronic hepatitis B:
      relation with HBV genotypes].

PMID- 15981623
TI  - [Helicobacter pylori infection and development of gastric cancer].

PMID- 15981624
TI  - [Gene alteration in gastric cancer].

PMID- 15981625
TI  - [A case of primary gastric plasmacytoma].

PMID- 15981626
TI  - [A case of duodenal gastrinoma asymptomatically detected by medical health
      check].

PMID- 15981627
TI  - [An autopsy case of AL amyloidosis with intestinal pseudo-obstruction].

PMID- 15981628
TI  - [A case of pneumatosis cystoides intestinalis and intestinal pseudo-obstruction
      in overlap syndrome manifested by polymyositis and scleroderma].

PMID- 15981629
TI  - [A case of primary hepatic lymphoma associated with chronic hepatitis C and a
      review of Japanese literature].

PMID- 15981630
TI  - [An autopsy case of rapid progressed cholangiolocellular carcinoma].

PMID- 15981631
TI  - [A case of acute hepatitis E who had a history of frequent ingestion of raw meat
      and viscera from wild deer and boars].

PMID- 15981632
TI  - [A case report of upper gastrointestinal bleeding from hemorrhagic pancreatic
      pseudocyst by penetration to the stomach].

PMID- 15981633
TI  - [A case of anaplastic ductal carcinoma (giant cell carcinoma of osteoclastoid
      type) with portal vein and main pancreatic ductal invasion].

PMID- 15981634
TI  - [Introduction: how to examine a patient with cognitive disorders].

PMID- 15981635
TI  - [How to make a differential diagnosis of the aphasic syndromes].

PMID- 15981636
TI  - [Responsible focus of apraxia].

PMID- 15981637
TI  - [Clinical assessment of agnosia].

PMID- 15981638
TI  - [Neuroimaging present and future].

PMID- 15981639
TI  - [Stress and central neuroendocrine networks].

PMID- 15981640
TI  - [Dementia and driving: present status of drivers with dementia and response of
      their family's care in Japan].
AB  - As a result of the growing proportion of drivers aged 65 years and older, it is
      estimated that the number of elderly drivers with dementia is increasing in
      Japan. Since June 2002, if a driver is found to be "demented", his/her driving
      license shall be revoked in Japan. However, there are no consensus guidelines for
      demented drivers. Between September 1995 and September 2001, we evaluated 30
      drivers with dementia (19 males and 11 females, mean age of 69.4 years) in out
      patients clinic of the Kochi Medical School Hospital and related hospitals.
      Clinical Diagnosis was Alzheimer's disease in 20, vascular dementia in 3, mixed
      type dementia in 2, frontotemporal lobar degeneration in 4, other type dementia
      in 1. We analyzed their driving behavior and family's attitude. Seventy-three
      point three percent of 30 drivers with dementia continued to drive after
      diagnosis. In follow-up periods, number of drivers continuing driving was
      decreased to 13 (43.3%), while six drivers (27.3%) had a traffic accident or
      violation. Our study suggests that several important medical and social factors
      should be considered for the management of drivers with dementia. A consensus
      medical guideline for demented drivers has to be established.

PMID- 15981641
TI  - [Japanese CADASIL case with limited dementia who had the Notch 3 R141C mutation].
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by
      recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia
      caused by point mutations of the Notch 3 gene. Here, we report a Japanese CADASIL
      case who displayed limited dementia and had the Notch 3 R141C mutation. The
      relationship between pathogenesis and the mutation site in Notch 3 is discussed
      based on the case presented here.

PMID- 15981642
TI  - [Reversible increased signal intensities in the splenium on diffusion-weighted
      imaging caused by transient hypoglycemia].

PMID- 15981643
TI  - [A case of 51-year-old woman demonstrating akinetic mutism with seven years
      course of Parkinsonism].

PMID- 15981645
TI  - [Bases of the activation of cerebral circulation].

PMID- 15981644
TI  - [Arrhythmias in the elderly population and their management].

PMID- 15981646
TI  - [Biological diagnositic markers for Alzheimer's disease].

PMID- 15981647
TI  - [Mechanism of atherosclerosis].

PMID- 15981648
TI  - [Terminal care of the elderly].
AB  - In 2001, the Japan Geriatrics Society released its position statement regarding
      the terminal care of the elderly. In the statement, it is stated as a technical
      issue that any medical practice implemented in terminal care should warrant its
      profit to the patient (position 6). Standardization of all medical practices and
      methods of care for dying patients is desired, and should be based upon
      scientific evidence regarding the profitability of the practice for the patient.
      The standardization of care should aim to exclude physicians' arbitrariness and
      to endorse patients' autonomy. However, healthcare systems and related scientific
      evidences that warrant patients' autonomy have not been sufficiently established
      in Japan. Under the circumstances, we have been engaging in research into the
      terminal care for older adults from 1997 to date by formulating a research team
      working under the scheme of comprehensive research project for longevity sciences
      funded by the ministry of health, labor and welfare. This article reviews
      findings achieved mainly from the research carried out by the members of the
      research team.

PMID- 15981649
TI  - [Strategy for influenza in the aged].

PMID- 15981650
TI  - [Relationship of the community in National Center for Geriatrics and
      Gerontology].
AB  - Acute hospital has to have a good community relationship because of looking for a
      services and settings after discharge for elderly patients. In particular,
      physicians should have good relations with other physicians, visiting nurses, and
      care managers, because elderly patients had to go to facilities or nursing homes
      instead of their own homes. We must obtain information concerning care services
      and build networks between hospitals and the community in order to provide good
      services. To enable this we established a good discharge support team. We also
      have to educate the staff and care managers to take good care of patients. A
      comprehensive geriatrics and team approach is important for geriatric medicine in
      the community through care conference. So geriatricians must take part in care
      conferences and take a leadership role in networks for people with care needs.
      Finally our national center for geriatrics and gerontology has to take a role of
      the future achievement in geriatric field and provide information related
      research and clinical activity for the elderly.

PMID- 15981651
TI  - [Mass health check-ups for maintenance of functional capacity and for prevention
      of long-term care dependence among the elderly].

PMID- 15981652
TI  - [Collaboration between a local medical community and a university hospital].
AB  - Here we report the current status and problems in collaboration between a local
      medical community and a university hospital. It is important for the university
      hospital to clearly define its role in the local medical community, collaborate
      with local medical and welfare institutes and establish a local medical and care
      network that supports patients and their families. For this purpose, the social
      service department is expected to play a role as a coordinator between the
      university hospital and the local medical community so that the patients can make
      the best use of medical and care resources.

PMID- 15981653
TI  - [Clinical information system and regional cooperative medicine].
AB  - By sharing medical information safely and appropriately with in a region, we
      constracted a system which provides an increase in efficiency of patient service,
      and improvement in the quality and efficiency of medical treatment. Even if a
      patient consults two or more hospitals, medical chart information is unified in
      the center and the continuity of the medical records is ensured. Patients can
      peruse their own charts from home, which is useful for informed consent.

PMID- 15981654
TI  - [Proposal about attempt of regional cooperation on dementia and geriatrics].

PMID- 15981655
TI  - [Present situation and problems of the home care nursing service for elderly
      people].

PMID- 15981656
TI  - [Care management to improve degrees of care needs].

PMID- 15981657
TI  - [Our town].

PMID- 15981658
TI  - [Care management sheet pack for the elderly with dementia: The Center Method ver.
      03].

PMID- 15981660
TI  - [Characteristics and limitation of portable bedside swallowing test in elderly
      with dementia: comparison between the repetitive saliva swallowing test and the
      simple swallowing provocation test].
AB  - Several bedside portable swallowing tests have been advocated for screening for
      dysphagia. However, the clinical usefulness and limitation of these tests have
      not been examined in elderly patients with dementia. We performed the repetitive
      saliva swallowing test (RSST) and the simple swallowing provocation test (SSPT)
      in 37 elderly inpatients (81.8 +/- 1.2 years old). Simultaneously, cognitive and
      verbal communication ability were assessed by the Hasegawa Dementia Scale revised
      version (HDSR) and the Mini-Communication Test (MCT). RSST was completed only in
      22 patients (59%), whereas SSPT was successfully completed in all cases. Scores
      of HDSR and MCT were significantly lower in patients who were unable to cooperate
      with RSST compared to successful examinees (HDSR: 7 +/- 1 vs 15 +/- 3, p < 0.0;
      MCT: 47 +/- 8 vs 81 +/- 5, p < 0.01). Dysphagia was detected in 14 patients (64%)
      by RSST and 5 (14%) by SSPT. Patients with dysphagia showed significantly lower
      cognitive function (p < 0.05) and verbal communication ability (p < 0.05). In
      conclusion, RSST is more sensitive to detect dysphagia in elderly patients;
      however, compliance with RSST is strongly influenced by the patient's cognitive
      function and verbal communication ability. Comprehensive geriatric assessment
      will help to choose an alternative test for dysphagia such as SSPT which is more
      specific test for aspiration pneumonia.

PMID- 15981659
TI  - [The economic and social costs of home care services].

PMID- 15981661
TI  - [Factors affecting subjective satisfaction with verbal communication among the
      disabled elderly and their family caregivers].
AB  - The aims of the present study were to investigate satisfaction with verbal
      communication among the disabled elderly and their family caregivers; and to find
      the significantly influential factors of satisfaction with verbal communication.
      The subjects were 85 disabled elderly and 85 family caregivers. For the disabled
      elderly, satisfaction with verbal communication, demographic, and physical
      factors were examined using an interview survey. For the caregivers, satisfaction
      with verbal communication, demographic factors, and some factors related
      caregiving were examined using a self-administered questionnaire. In the disabled
      elderly, 82.4% were satisfied with their verbal communication while 55.3% of
      family caregivers were satisfied. Satisfaction with verbal communication between
      the disabled elderly and their caregivers showed low agreement (kappa = 0.17).
      Bivariate analysis revealed that satisfaction with verbal communication of the
      disabled elderly was significantly related to ADL (p < 0.01), dysphagia risk (p <
      0.05), and ability of comprehension (p < 0.05) while satisfaction with verbal
      communication of caregivers was significantly related to the gender of the
      disabled elderly and caregivers' burden. Furthermore, multiple regression
      analysis showed that the factor most related to satisfaction with verbal
      communication for the disabled elderly was ability of comprehension (p value =
      0.032, odds ratio = 2.960), and the most related factor for their caregivers was
      the burden evaluated by J-ZBI_8 (p value = 0.004, odds ratio = 0.842). These
      results suggest that satisfaction with verbal communication of the disabled
      elderly disagrees with that of the family caregivers, and that some related
      factors for the disabled elderly are different from those in their family
      caregivers.

PMID- 15981662
TI  - [The influence of a doctor's opinion on notification delay in the long-term care
      insurance system in Japan--a two year study].
AB  - Prompt notification of recognition of the need for nursing is necessary for
      smooth application of Long-term Care Insurance Services. The Long-term Insurance
      Act requires notification of applicants of certification within 30 days. However,
      recognition of the need actually may be delayed for various reasons. To explain
      the influence of investigation for certification and the doctor's opinion for
      notification delay, 38,285 applications were investigated for 2 years in a city
      close to Osaka. The investigation period was divided into two stages, the first
      stage (from July 2000 to June 2001) and the second stage (from July 2001 to June
      2002). The notification rate of the recognition result within 30 days was 42.0%
      in the first stage, and it improved to 46.8% in the second stage. However, the
      approximate number of days required for investigation for certification improved
      from 10.5 to 10.3, and that for the doctor's opinion improved from 20.2 to 19.1.
      Thus the doctor's opinion is a rate-controlling factor for the notification. By
      the standard operating procedures of the city, a two-week period is needed to
      prepare the long-term care requirement certification, thus it is necessary to
      obtain the doctor's opinion within 15 days.

PMID- 15981663
TI  - [Awareness of dementia in older adults attending dementia-prevention programs in
      community healthcare centers].
AB  - Recently, the dementia-prevention program hosted by the Ministry of Health,
      Welfare and Labor has been widely implemented. We administered a questionnaire to
      347 elderly adults (mean age: 71, mean MMSE score: 27.2) who attended programs in
      community healthcare centers. The questionnaire consisted of questions
      concerning: (1) belongings (2) knowledge about dementia (3) opinions about
      revealing the diagnosis of dementia to patients (4) anxiety for own onset of
      dementia. Regarding the knowledge about dementia, 17% of the participants knew
      about drug therapy, and 13% of them knew about legal guardianship. The results
      indicated a limited knowledge about facilities where demented people can be
      placed (home: 39%, hospital: 43%, nursing home: 62%, group-home: 25%). As for
      revealing the diagnosis, 68% of the participants hoped they would be informed of
      the diagnosis if they become demented, while 66% of them felt anxiety about
      having dementia in the future. In terms of difference by age (> or = 70 v.s. < or
      = 69), while the older group had low knowledge about the facilities and felt more
      anxiety about their own onset of dementia (chi2 test p < 0.05, Mann-Whitney U
      test p < 0.05), there were no intergroup difference regarding their expectations
      of being told about the diagnosis of dementia. Overall, the results of the
      questionnaire suggest that appropriate education of dementia to older adults may
      contribute to early diagnosis of the community level, thereby may maximize the
      effect of therapeutic interventions.

PMID- 15981664
TI  - [Development of a portable fall risk index for elderly people living in the
      community].
AB  - AIM: To develop a portable risk index for falls. METHODS: Risk factors were
      chosen from previously established factors then we added several environmental
      factors to the risk index; previous falls in the last 12 month, trippig or
      stumbling, inability to ascend or descend stairs without help, decreased walking
      speed, inability to cross a road within the green signal interval, inability to
      walk 1km without a break, inability to stand on one leg for 5 seconds (eyes
      open), using a cane, inability to wring out a towel, dizziness or faintness,
      stooped or rounded back, knee joint pain, visual disturbance, hearing
      disturbance, cognitive decline, fear of falling, receiving 5 or more prescribed
      drugs, sensation of darkness at home, obstacles inside, barrier on the carpet or
      floor, using steps daily at home, steep slopes around home. SUBJECTS: The
      questionnaire sheet was completed by 2,439 community-dwelling elderly subjects
      (76.3 +/- 7.4 years old). The frequency of each items of fall risk index was
      compared between fallers (history of fall within one year) and non-fallers.
      Multiple regression analysis was performed to identify independent risk factors
      for previous falls. RESULTS: Except barrier, step use and steep slope around
      home, all items in the fall risk index were more frequent in fallers.
      Multivariate analysis revealed that tripping or stumbling, inability to cross a
      road within the green signal interval, dizziness or faintness, obstacles inside,
      inability to wring out a towel, cane use and knee joint pain were independent
      risk factors for previous falls. These 7 selected items were further analyzed as
      predictors. The maximum sum of sensitivity and specificity was reached at the cut
      off point of 2/3 (sensitivity 0.65, specificity 0.72) by receiver operating
      curve. CONCLUSION: Portable fall risk index is useful for clinical settings to
      identify high-risk subjects.

PMID- 15981665
TI  - [An epidemiological study of the relationship between the number of remaining
      teeth and the disabled elderly receiving long-term care].
AB  - This study attempts to clarify the relationship between the long-term care of the
      elderly and the number of remaining teeth by comparing the remaining teeth of the
      healthy with that of the disabled elderly. A survey was conducted in a town,
      Fukuoka Prefecture. The disabled group consisted of 62 persons with level of
      disability of 4-5 according to the Long-term Care Insurance categorization.
      Controls were selected randomly from healthy elderly residents, one for each in
      the disabled group, matching gender and age (less than +/- 1 year old). Public
      health nurses conducted interviews using a questionnaire to determine the cause
      of disease, medical history, lifestyle and period of long-term care, and counted
      the remaining teeth. The mean number of remaining teeth presented a significant
      difference with 3.7 for the disabled group and 9.1 for the control group (p <
      0.01). A logistic regression analysis revealed that the odds ratio for long-term
      care to that of the reference with 20 or more teeth was 7.03 (95% CI: 1.15-42.85)
      for 10 to 19 teeth, 15.61 (2.89-84.26) for 1 to 9 teeth, and 15.11 (2.84-80.48)
      for no teeth. The age group of 65-69 years and 70-79 years in the disabled group
      had significantly smaller mean numbers of remaining teeth than their control
      group counterparts by approximately 14 and 12 respectively, but in the age group
      of 80 years or more, no significant difference was observed between the two
      groups. In conclusion, our results suggested that elderly people with fewer
      remaining teeth have a high risk for long-term care. Especially, the risk was
      thought to be strongly associated with the loss of some teeth in middle age.

PMID- 15981666
TI  - [A case of interval form of carbon monoxide poisoning with a remarkable
      recovery].
AB  - A 69-year-old woman was admitted to our hospital due to an interval form of
      carbon monoxide (CO) poisoning one month after acute CO poisoning. On admission,
      she had disorientation, memory disturbance, apathy, masked face, muscle rigidity,
      bradykinesia and parkisonian gait. An MRI (FLAIR image) revealed high signal
      intensity lesions in the bilateral globus pallidus and the white matter of the
      frontal lobe. Hyperbaric oxygen (HBO) therapy at 2 atmospheres for 60 min was
      given every day, in addition to citicoline, levodopa/DCI and selegiline
      hydrochloride. Cognitive disturbance and parkinsonism gradually decreased, and
      abnormal signals in the bilateral globus pallidus and the cerebral white matter
      were attenuated after the treatment. Neuropsychiatric abnormalities except for a
      slight gait disturbance disappeared one and a half month after starting the
      treatment. In addition to HBO therapy, administration of citicoline, lovodopa and
      selegiline may be useful in the case of the interval form of CO poisoning.

PMID- 15981667
TI  - [A case of sarcoidosis in which sarocoid granulomas were observed only in the
      heart].
AB  - A 64-year-old woman was transferred to the intensive care unit with dyspnea and
      palpitation on effort. Chest x-ray film showed cardiomegaly and pulmonary
      congestion. We carefully examined for sarcoidosis as a differential diagnosis of
      heart failure. Serum lysozyme was mildly high, but human atrial natriuretic
      peptide (HANP) and brain natriuretic peptide (BNP) were strikingly high.
      Angiotensin converting enzyme was within normal limit. Chest roentgenogram did
      not reveal bilateral hilar lymphadenopathy. Atrioventricular conduction block was
      not observed on electrocardiogram. Echocardiographic examination showed left
      ventricular global hypokinesis with septal thinning and enlargement. Mitral valve
      regurgitation was recognized by Doppler evaluation. Coronary arteriography showed
      normal coronary arteries. Endomyocardial biopsy revealed noncaseous epithelioid
      granulomas containing, Langhans type giant cell accompanied by fibrosis and
      lymphocyte infiltration. From these data cardiac sarcoidosis was diagnosed.
      Gallium scintigraphy showed diffuse uptake only in the heart. Treatment with oral
      prednisolone 20 mg/day was started. Her symptoms improved by several weeks after
      the medical treatment. In addition, both the value of HANP and BNP were markedly
      decreased and echocardiogram showed improvement of cardiac systolic function. In
      Japan, there is a higher incidence of cardiac sarcoidosis than in the West. The
      prognosis of this condition associated with cardiac dysfunction is reported to be
      very poor. When progressive heart failure in older patients is seen, cardiac
      sarcoidosis should also be kept in mind. Endomyocardial biopsy play an important
      role as the only accurate technique for the diagnosis of cardiac sarcoidosis.

PMID- 15981668
TI  - PET and cancer screening.
AB  - Various carcinomas are discovered incidentally during FDG PET study. This points
      to the potential use of PET as a cancer screening modality. Our experience using
      three PET scanners showed that PET can be performed in many individuals, and a
      wide variety of carcinomas can be detected at potentially curable stages. PET
      screening targets various organs that conventional organ-specific screening tests
      cannot cover. PET used simultaneously with conventional tests can prevent the
      overlooking of cancer, reduce false-positive results, and assist in the
      interpretation of CT and MR images. Thus, PET can play a supportive role when
      used with conventional screening tests. To reduce false-positive and false
      negative results in PET screening, however, experienced PET oncologists who can
      differentiate between distinct physiological FDG uptake and faint abnormal FDG
      uptake are needed. In Japan, more than half of the PET facilities offer PET
      examinations for cancer screening of asymptomatic persons. Not a few individuals
      pay for sophisticated cancer screenings. Guidelines concerning the use of PET for
      cancer screening were issued by the Japanese Society of Nuclear Medicine in 2004.
      The guidelines provide for maintenance of study quality and warn of overselling
      PET screening. It is unclear how much PET contributes to sophisticated cancer
      screening. Data are lacking as to whether mortality is reduced by PET screening.
      Scientific evidence should be presented demonstrating the value of PET in cancer
      screening.

PMID- 15981669
TI  - Usefulness of whole PTH assay in patients with renal osteodystrophy--correlation
      with bone scintigraphy.
AB  - OBJECTIVE: Intact parathyroid hormone (PTH) assay has recently been reported to
      be effective in evaluating both 1-84 PTH (whole PTH) and inactive 7-84 PTH.
      Inactive 7-84 PTH is considered to be increased in hemodialysis patients and to
      prevent the effects of 1-84 PTH, and intact PTH is considered to overestimate the
      PTH activity in these patients. As such, a whole PTH assay has recently been
      developed. The purpose of this study was to examine the usefulness of a whole PTH
      assay using the bone to soft tissue (B/ST) ratio on bone scintigraphy. METHOD:
      Twenty-five hemodialysis patients were included in our study. In all patients,
      bone scintigraphy and a blood test [whole PTH, intact PTH, alkaline phosphatase
      (ALP), calcium (Ca), and phosphorus (P)] were performed. Regions of interest
      (ROIs) were drawn around the cranium, lumbar vertebrae, left femoral neck, and
      soft tissue of the medial left thigh to obtain the B/ST ratio. RESULTS: The B/ST
      ratio of the cranium and left femoral neck correlated with whole PTH and intact
      PTH. In particular, the B/ST ratio of the cranium correlated most significantly
      with the value of whole PTH. Whole PTH levels correlated with intact PTH levels
      (r = 0.891, p < 0.0001). CONCLUSION: Our data indicate that a whole PTH assay may
      be useful in evaluating PTH activity using the B/ST ratio. The B/ST ratio of the
      cranium may reflect the bone metabolism of hemodialysis patients.

PMID- 15981670
TI  - Dual-radionuclide simultaneous gastric emptying and bile transit study after
      gastric surgery with double-tract reconstruction.
AB  - OBJECTIVE: The physiology of gastrointestinal transfer function after proximal
      gastrectomy with bypass-tract reconstruction is not well understood. We applied a
      simultaneous dual-radionuclide method with a hepatobiliary imaging and gastric
      emptying study to evaluate physiologic alterations occurring after surgery.
      METHODS: Nineteen patients with early gastric cancer, including 9 preoperative
      control patients and 10 who had proximal gastrectomy and double-tract
      reconstruction surgery were examined by dual-radionuclide hepatobiliary and
      gastric emptying studies (99mTc PMT and 111In DTPA). Retention fraction in the
      stomach at 3 minutes (R3) and 60 minutes (R60) and gastric emptying half-time
      (GET) were calculated. Bile reflux and mixture of bile and food were also
      evaluated. RESULTS: The retention fractions of R3 and R60 were significantly
      lower in the double-tract reconstruction group than those in the preoperative
      group. GET differed significantly between the double-tract and preoperative
      groups (20.7 min +/- 7.1 min and 36.2 min +/- 11.0 min, p = 0.0018). The mixture
      of bile and food was not good in the double-tract reconstruction group (p = 0.014
      vs. preoperative). Patients with a large residual stomach showed slower initial
      emptying (p = 0.0068) and a better mixture of bile and food (p = 0.058) compared
      to those with a small residual stomach. The bile reflux was not significantly
      increased after surgery. CONCLUSION: The dual-radionuclide gastrointestinal and
      hepatobiliary imaging was feasible and could demonstrate characteristic transit
      patterns of the foods and bile in the double-tract reconstruction procedure. A
      larger residual stomach, if possible, is desirable to provide better transfer and
      mixing of bile and foods.

PMID- 15981671
TI  - Evaluation of alveolo-capillary permeability in thyrotoxicosis using Tc-99m DTPA
      aerosol scintigraphy.
AB  - Surfactant secreted from type II pneumocytes plays an important role in alveolo
      capillary permeability. In thyrotoxicosis, high levels of T3 receptors detected
      at these cells might affect the alveolo-capillary permeability due to increased
      serum thyroid hormone levels. The results by CO-diffusion capacity measurement in
      thyrotoxicosis are conflicting. Changes in alveolo-capillary membrane
      permeability resulting from thyrotoxicosis are not well established yet. This
      prompted us to investigate the alveolo-capillary permeability in thyrotoxic
      patients in comparison with CO-diffusing capacity. For this aim twenty-two non
      smoking thyrotoxic patients (before treatment) and fifteen healthy voluntary
      controls underwent 99mTc-DTPA aerosol scintigraphy. CO-diffusing and pulmonary
      function tests were performed in all subjects. After ventilation of radiotracer
      through a nebulizer for 15 minutes, 30 dynamic images (1 frame/minute) were taken
      from both lungs. ROI's were drawn over both lung areas, and the time-activity
      curves were generated. Then clearance half time (CT1/2) for radioaerosol was
      obtained. CT1/2 of thyrotoxic patients did not differ from that of the controls:
      77.9 +/- 25.9 min vs. 79.4 +/- 22.3 min; p > 0.05. Similar result was found for
      CO-diffusion parameters. Also there was no significant correlation between CT1/2
      and CO-diffusion parameters. We concluded that in patients with thyrotoxicosis,
      the alveolo-capillary permeability is unaffected. Further experimental research
      is needed to establish the possible effects of thyroid hormones on alveolo
      capillary membrane.

PMID- 15981672
TI  - Radiopharmaceutical model using 99mTc-MIBI to evaluate amifostine protection
      against doxorubicin cardiotoxicity in rats.
AB  - The aim of our study was to use an in vivo radiopharmaceutical model to
      investigate the cytoprotective effect of amifostine against doxorubicin-induced
      cardiotoxicity. Male Wistar rats were randomly divided into four groups (n = 6):
      1) Saline (control); 2) Doxorubicin (DOX; 10 mg/ kg(-l) intraperitoneally); 3)
      Amifostine (AMI; 200 mg/kg(-1) intraperitoneally); 4) Doxorubicin plus amifostine
      (DOX + AMI). Amifostine was injected 30 minutes before doxorubicin in Group 4.
      99mTc-MIBI, 20 MBq/0.2 ml(-1), was injected through the tail vein 72 hours after
      the drug administration. Rats were killed and samples of myocardium were removed
      by dissection 60 minutes after the injection of radiopharmaceutical.
      Radioactivity in each organ sample was counted using a Cd(Te) detector equipped
      with RAD 501 single-channel analyzer. The percent radioactivity was expressed as
      a percentage of the injected dose per gram of tissue (%ID/g(-1)). The %ID/g(-1)
      activity was calculated by dividing the activity in each sample by the total
      activity injected and mass of each organ. 99mTc-MIBI uptake as %ID/g(-1) was
      1.194 +/- 0.502 and 0.980 +/- 0.199 in the control and AMI groups, respectively.
      Doxorubicin administration resulted in a significant increase in %ID/ g(-1)
      (3.285 +/- 0.839) (p < 0.05). Amifostine administration 30 minutes before
      doxorubicin injection resulted a significant decrease in %ID/g(-1) (2.160 +/-
      0.791) (p < 0.05) compared with doxorubicin alone. The results showed that
      amifostine significantly attenuated doxorubicin-induced cardiotoxicity.

PMID- 15981673
TI  - Evaluation of myocardial perfusion in patients with Behcet's disease.
AB  - AIM: To estimate the prevalence of silent myocardial ischemia (SMI) in patients
      with Behcet's disease (BD) and to identify a subgroup of patients at higher risk
      for the presence of SMI. MATERIALS AND METHODS: We evaluated 41 patients (mean
      age 42.8 +/- 12.3 years) with BD and 35 healthy control subjects. Treadmill
      exercise test and thallium-201 myocardial perfusion single photon emission
      computed tomography (SPECT) were performed in all subjects. Coronary angiography
      was performed in all patients with a diagnosis of SMI in Behcet's group. RESULTS:
      All subjects had normal resting electrocardiograms. Eight patients with BD
      (19.5%) had evidence of ischemia on exercise testing and myocardial perfusion
      SPECT. Only one SMI positivity (2.9%) was recorded in the control group.
      Significant coronary stenosis was not found with coronary angiography in the
      patients with a diagnosis of SMI in Becet's group. SMI positivity was recorded in
      2 of 18 female patients (11%) and in 6 of 23 male patients (26.1%) with BD (p =
      0.429). The mean duration of BD was 13.8 +/- 2.6 years in patients with SMI and 7
      +/- 4.1 in patients without it (p < 0.001). Seven of the 8 patients (87.5%) with
      SMI had a duration of BD of greater than 10 years. CONCLUSIONS: The results of
      this study show that the prevalence of SMI is high in patients with BD. Based on
      our findings, screening with myocardial perfusion scintigraphy may be recommended
      for patients with duration of BD greater than 10 years.

PMID- 15981674
TI  - Three-dimensional registration of myocardial perfusion SPECT and CT coronary
      angiography.
AB  - OBJECTIVE: In this study, we describe a new technique for three-dimensional
      registration of CT coronary angiography (CTCA) and gated myocardial perfusion
      SPECT. METHODS: Twelve patients with known or suspected CAD who underwent CTCA
      and gated SPECT were enrolled retrospectively. Coronary arteries and their
      branches were traced using CTCA data manually and reconstructed in three
      dimensions. Gated SPECT data were registered and mapped to a left ventricle
      binary model extracted from CTCA data using manual, rigid and nonrigid
      registration methods. RESULTS: Three-dimensional reconstruction and volume
      visualization of both modalities were successfully achieved for all patients. All
      3 registration methods gave better quality based on visual inspection, and
      nonrigid registration gave significantly better results than the other
      registration methods (p < 0.05). The cost function for three-dimensional
      registration using nonrigid registration (235.3 +/- 13.9) was significantly
      better than those of manual and rigid registration (218.5 +/- 15.3 and 223.7 +/-
      17.0, respectively). Inter-observer reproducibility error was within acceptable
      limits for all methods, and there were no significant difference among the
      methods. CONCLUSION: This technique of image registration may assist the
      integration of information from gated SPECT and CTCA, and may have clinical
      application for the diagnosis of ischemic heart disease.

PMID- 15981675
TI  - Use of iodine-123 metaiodobenzylguanidine scintigraphy for the detection of
      amiodarone induced pulmonary toxicity in a rabbit model: a comparative study with
      technetium-99m diethyltriaminepenta acetic acid radioaerosol scintigraphy.
AB  - The purpose of the study was; (i) to determine whether 123I-MIBG scintigraphy is
      sensitive for detection of amiodarone induced pulmonary toxicity (AIPT) and (ii)
      to compare it with 99mTc-DTPA radioaerosol. Twelve white New Zealand rabbit with
      initial mean body weight 4.24 +/- 0.47 g were divided into two groups. AIPT group
      (n = 7) was administered amiodarone (20 mg/kg BW). The control group (n = 5)
      received the same amount of 0.9% saline. All animals underwent 123I-MIBG and
      99mTc-DTPA radioaerosol scintigraphy at the end of the treatment period. 123I
      MIBG static thorax images were obtained during 10 minutes at 15 minutes and 3
      hours after intravenous injection of the radiopharmaceutical. Lung to heart
      ratios (LHR) and lung to mediastinum ratios (LMR), and retention index (LRI) of
      123I-MIBG were determined. Two days after 123I-MIBG scintigraphy, 99mTc-DTPA
      radioaerosol scintigraphy was performed, and clearance from the lungs was
      measured for 10 min (1 min/frame) following termination of inhalation. 123I-MIBG
      lung retention index (LRI) was significantly higher in the AIPT group than the
      control (61 +/- 4.6 vs. 40 +/- 4.5, p = 0.01). Early LHR and LMR were
      significantly lower in the AIPT group than in the control group (p = 0.04, p =
      0.01, respectively), whereas those of late LHR and LMR were not significantly
      different. T1/2 values of DTPA clearance were significantly increased in AIPT
      group according to the control group (55 +/- 7.2 vs. 86.6 +/- 18.5, p = 0.02).
      123I-MIBG scintigraphy is a valuable tool for detecting AIPT in a rabbit model.
      Additionally, 99mTc-DTPA radioaerosol scintigraphy is an excellent comprehensive
      investigational tool for detecting AIPT with the added advantage of lower cost.

PMID- 15981676
TI  - Metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease also decreases at
      thyroid.
AB  - BACKGROUND: Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported
      in Parkinson's disease and this contributes to the differential diagnosis between
      Parkinson's disease and other forms of parkinsonism such as multiple system
      atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated.
      OBJECTIVE: To compare MIBG uptake of the thyroid among Parkinson's disease,
      multiple system atrophy and controls. METHODS: Twenty-six patients with
      Parkinson's disease, 11 patients with multiple system atrophy and 14 controls
      were examined in this study. Planar images were taken 15 minutes (early images)
      and 3 hours (late images) after intravenous injection of 111 MBq 123I-MIBG.
      RESULTS: MIBG uptake of the thyroid on early images decreased significantly in
      Parkinson's disease compared to controls (p < 0.0001) and multiple system atrophy
      (p = 0.018). MIBG uptake of the thyroid on early images decreased significantly
      also in multiple system atrophy compared to controls (p = 0.027). On late images,
      thyroid uptake differed significantly only between Parkinson's disease and
      controls (p = 0.010). CONCLUSIONS: Our study is the first to demonstrate
      decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous
      denervation of Parkinson's disease occurred not only in the heart but also in the
      thyroid.

PMID- 15981677
TI  - Crossed cerebellar glucose hypermetabolism demonstrated using PET in symptomatic
      epilepsy--case report.
AB  - A 65-year-old male with an old cerebral contusion in the frontal lobes had
      suffered from status complex partial seizures. Ictal positron emission tomography
      with an F-18 fluorodeoxyglucose ([18F]FDG-PET) scan revealed hypermetabolism in
      the frontal, temporal and parietal lobes and the contralateral cerebellar
      hemisphere. The patient underwent a next-day PET scan with the 15O-labeled gas
      inhalation technique, which showed mild hyperperfusion and oxygen hypermetabolism
      in these areas. An interictal [18F]FDG-PET scan 17 days after the initial
      epilepsy demonstrated glucose hypometabolism of the frontal, temporal and
      parietal lobes and the contralateral cerebellar hemisphere. Increased glucose
      metabolism on the interictal PET scan and decreased glucose metabolism on an
      interictal PET scan in the epileptogenic supratentorial zones and the
      contralateral cerebellar hemisphere are interesting observations for
      understanding the pathophysiology in long-standing partial seizures.

PMID- 15981678
TI  - Varices of inferior epigastric veins caused by chronic inferior vena cava
      obstruction: mimicking normal venous flow pattern on radionuclide venography.
AB  - A 21-year-old patient with long-standing inferior vena cava obstruction secondary
      to idiopathic thrombosis extending from the external iliac veins underwent a
      radionuclide venography with Tc-99m pertechnetate labeled erythrocytes. The blood
      pool phase of the study revealed bilaterally distorted inferior epigastric veins
      mimicking normal venous flow pattern. The authors present this case to discuss
      the possible alternative routes and the underlying physiopathologic mechanism of
      this unusual flow pattern in chronic inferior vena cava obstruction.

PMID- 15981679
TI  - Unexpected abnormal extra-cardiac mediastinal accumulation of technetium-99m
      tetrofosmin in patient with acute pericarditis.
AB  - A 58-year old woman had felt some chest pains on effort for several days. She was
      admitted to the emergency room with severe and refractory chest pain after
      exercise. Electrocardiogram showed marked ST-segment elevations in II, III, aVF
      and V1-6 electrodes. Echocardiogram revealed neither wall motion asynergy in the
      left ventricle nor abnormal pericardial effusion. Chest X-ray showed normal
      findings, and mild elevation of C-reactive protein was observed in the blood
      chemistry data. Her chest pain was relieved by nitroglycerin administration.
      Emergent technetium-99m-tetrofosmin myocardial imaging did not show any abnormal
      perfusion in the left ventricle. However, an abnormal extra-cardiac mediastinal
      accumulation was detected in the planar image. Contrast-enhanced chest CT
      scanning also demonstrated an inhomogeneously enhanced tumor in the anterior
      superior mediastinum. The tumor was surgically removed and was finally diagnosed
      as an invasive thymoma. Technetium-99m-tetrofosmin scintigraphy happened to
      provide useful information for diagnosing acute pericarditis with mediastinal
      tumor.

PMID- 15981680
TI  - Dilated cardiomyopathy relieved as a result of beta-blocker therapy: a case
      report--key points in assessment of prognosis based on MIBG myocardial
      scintigraphy and BNP levels.
AB  - A 48-year-old male patient was admitted to our hospital with dyspnea accompanied
      by orthopnea. Chest x-rays showed a cardiothoracic ratio of 68% and pulmonary
      congestion. He was diagnosed with dilated cardiomyopathy. Beta-Blocker
      (carvedilol) therapy was initiated on Day 22 of the disease using a small initial
      dose. He was followed up based on BNP levels and MIBG scintigraphy. The H/M ratio
      and MIBG washout rate were 1.98 and 33.4%, respectively, on Day 20 and 2.15 and
      28.1%, respectively, on Day 72. The patient was discharged on Day 72 when
      congestive heart failure improved. Relatively high BNP levels were observed for 1
      month after starting treatment with a beta-blocker. Plasma BNP levels were still
      as high when his heart failure was improved. BNP is useful as a convenient
      indicator for the severity of cardiac diseases. MIBG scintigraphy may be used
      thereafter to evaluate the severity in greater detail and more precisely
      determine the prognosis.

PMID- 15981681
TI  - Outcome of ablation of thyroid remnants with 100 mCi (3.7 GBq) iodine-131 in
      patients with thyroid cancer.
AB  - A retrospective study was conducted on 186 patients with differentiated thyroid
      cancer without metastases who received an ablative dose of 100 mCi (3.7 GBq)
      iodine-131 after total thyroidectomy. Six months to one year after ablation,
      155/186 patients (83%) had a negative scan. Diagnostic scanning with 5 mCi (185
      MBq) performed 72 h or 3 months before ablation did not interfere with treatment
      success compared to patients not submitted to pre-therapy scanning. Pre-ablation
      cervical uptake values < 2% were associated with a higher ablation efficacy
      (94%), from 2 to 5% showed 80% success and values > 5%, 60% (p < 0.05). There
      were no significant differences between the responsive and no responsive groups
      in terms of age, sex, histological type or size of the primary tumor. 11% of the
      patients with low stimulated Tg (< 2 ng/ml) presented discrete thyroid bed uptake
      on follow-up diagnostic scan (< 0.5%) without definitive residual disease and 89%
      had negative uptake on scan. The patients with Tg > 2 ng/ml presented thyroid bed
      (10/12) or ectopic (2/12) uptake on follow-up diagnostic scan. An ablative dose
      of 100 mCi shows a high rate of efficacy, especially when cervical uptake is <
      2%; no difference was noted between patients assessed by scan within 72 h or 3
      months before treatment and those not scanned; follow-up diagnostic scan can be
      avoided in low risk patients with stimulated Tg < 2 ng/ml.

PMID- 15981682
TI  - Utility (or futility?) of electrodiagnosis in thoracic outlet syndrome.
AB  - The objective diagnosis of thoracic outlet syndrome (TOS) remains a challenge.
      The purpose was to present our experience and discuss the utility of
      electromyography, electroneurography and somatosensory evoked potentials after
      ulnar nerve stimulation in patients with surgically verified neurovascular
      compression at the thoracic outlet. Twenty patients (median age 29.5, 16 women)
      with operatively verified neurovascular compression by a cervical rib or band
      were examined. All complained of pain and paraesthesias in the hand. In 12
      vasomotor disturbances (pallor or lividity, low skin temperature, Raynaud's
      phenomenon) were also observed. Clinical diagnosis was supported by the
      provocative tests (Adson, Wright, costoclavicular) in 14persons. Neurologic signs
      were present in 2 patients in "pseudoulnar" distribution. Anterior scalenectomy
      was performed with success in 15 cases, 4 remained unchanged and 1 worsened.
      Electrodiagnostic tests were normal in all 18 patients without neurologic signs.
      We note a tendency for the digital nerves sensory action potentials in patients
      with TOS to be higher than usual It is concluded that electrodiagnosis is useless
      in confirming the presence of TOS, but it is very useful to exclude other painful
      conditions that require other treatments (carpal and cubital tunnel syndromes,
      cervical radiculopathies etc).

PMID- 15981683
TI  - Correlation between the size of the compound muscle and sensory nerve action
      potentials recorded from the foot in distal axonopathy.
AB  - Nerve conduction study was performed on 71 diabetic patients with distal
      sensorimotor axonopathy. Of 76 lower limbs studied, 46.1% showed no recordable
      sural compound sensory nerve action potential (CSNAP), and 55.3% no superficial
      peroneal CSNAP. Only 2.6% revealed no recordable compound muscle action potential
      (CMAP) from the abductor hallucis (AH) muscle, and 9.2% showed no obtainable CMAP
      from the extensor digitorum brevis (EDB) muscle. There were fairly good positive
      correlations between the amplitudes of the sural CSNAPs and AH CMAPs (r = 0.66),
      and between the superficial peroneal CSNAP and EDB CMAP amplitudes (r = 0.63).
      There were no instances in which a CSNAP could be obtained from the sural or
      superficial peroneal sensory nerve, but a CMAP could not be recorded from the AH
      or EDB muscle. If the CMAP amplitudes of the AH and EDB muscles were reduced to
      less than 0.3 mV, usually a CSNAP could longer be recorded from the sural and
      superficial peroneal sensory nerves. The size of the CSNAP is a more sensitive
      measure compared to the CMAP in revealing the presence of distal sensorimotor
      axonopathy.

PMID- 15981684
TI  - A sensitive new median-ulnar technique for diagnosing mild Carpal Tunnel
      Syndrome.
AB  - Carpal Tunnel Syndrome (CTS) is easily the most common focal peripheral nerve
      compression. The primary diagnostic tool is electrodiagnosis, although 13-27% of
      patients with symptoms and signs of CTS have normal electrodiagnostic results.
      The goal of this study was to create a more sensitive and specific latency
      difference criteria without any additional testing beyond the minimum.
      Statistical theory indicates that this would occur by comparing the latency most
      sensitive to CTS to the least sensitive latency. Data was evaluated from 68
      normal hands, 23 hands of patients with symptoms and signs of CTS but normal
      standard results, and 88 hands of patients with CTS symptoms and signs of CTS
      with the diagnosis confirmed with standard criteria. The Median Sensory latency
      was the most sensitive parameter, while the Ulnar Motor Latency varied least in
      the presence of CTS, making the (Median Sensory-Ulnar Motor) latency difference
      the criteria of choice. Setting a cutoff value of 0.8 msecs for this difference
      correctly classified all normals, and all hands with CTS by standard criteria,
      and classified as abnormal 19/23 (82%) of hands with symptoms and signs of CTS
      but negative results by standard criteria. Overall the (Median Sensory-Ulnar
      Motor) Latency difference is a simple, easy, sensitive and specific test for CTS.

PMID- 15981685
TI  - Peripheral neuropathy in systemic lupus erythematosus in Southern Iran.
AB  - The prevalence of clinically apparent peripheral neuropathy in systemic lupus
      erythematosus (SLE) is reported to be between 2-27%. The purpose of this
      descriptive cross sectional study was to determine the prevalence of peripheral
      neuropathy (PN) using electrodiangostic criteria in SLE in southern Iran.
      Subgroup analysis was performed to determine whether PN correlated with disease
      activity, serum immune markers and duration of disease and clinical findings. The
      right median, ulnar, peroneal, tibial and sural sensory and motor nerve
      conduction studies were conducted in 64 SLE cases. PN in our study was defined as
      any abnormal values in sensory action potential, motor action potential, or
      conduction velocity affecting 2 or more nerves. Of 64 patients studied, PN was
      present in 12 patients (18.7%), of which 4 (6.6%) were symptomatic. There was no
      significant correlation between PN and serum immune markers, and there was a
      trend showing decreased motor and sensory action potential amplitude in our SLE
      group compared to the controls. This observation was also seen in active disease
      group where compared to inactive disease. The amplitude of the action potential
      and then NCV were more often affected than distal latency, and sensory nerves
      were more susceptible than motor nerves and regarding the results
      electrodiognostic study is more sensitive than clinical evidence in detecting PN
      in SLE.

PMID- 15981686
TI  - Sensory and motor evoked potentials findings in patients with thoracic outlet
      syndrome.
AB  - OBJECTIVE: Diagnostic utility of somatosensory and motor evoked potentials in two
      patients with neurogenic and vascular thoracic outlet syndrome (TOS) were
      investigated. MATERIALS AND METHODS: In two female patients with progressive
      weakness and sensory disturbance of the arms, mixed nerve somatosensory evoked
      potentials (SSEP), and motor evoked potentials (MEP) were tested before and after
      dynamic position of the affected arm. RESULTS: The cortical and cervical (C7)
      ulnar SSEPs demonstrated no change in latency of major peaks at rest and after
      abduction of the shoulder. A slight diminishment of cortical amplitude was noted
      in the first patient after the dynamic position of the arm. The MEPs demonstrated
      significant drop in amplitude after dynamic position of the arm in both cases
      signifying neurovascular compression during elevation of the affected arm. No
      change in MEP latency was noted. The MEP amplitude completely returned to normal
      after repositioning the arm. CONCLUSIONS: Evoked potential studies are helpful in
      the diagnosis of neurogenic or vascular TOS. Reduced amplitude of MEP occurs
      after elevation of the arm above the head which improves after normal position of
      the arm.

PMID- 15981687
TI  - Bilateral sacral radiculopathy in a cyclist.
AB  - OBJECTIVE-PURPOSE: The purpose of this case report is to describe a gait disorder
      presenting as a bilateral sacral radiculopathy after vigorous cycling. Also, we
      discuss the pathogenic mechanisms and we revise the bibliography. PATIENT AND
      METHODS: The patient complained of a rapid painless weakness in legs, after
      intense and prolonged cycling 4 months ago. The physical and electromyographical
      examinations revealed important weakness in foot and knee flexors, and signs of
      acute denervation with mixed reinnervation (active and chronic) in myotomal S1
      muscles, respectively. The lumbo-sacral magnetic resonance imaging were normal.
      The follow-up studies demonstrated gradually improvement in clinical and
      neurophysiological parameters. DISCUSSION: We established that our patient
      presented a subacute bilateral S1 radiculopathy and we confirmed the progressive
      clinical and neurophysiological improvement. The radiculopathy are infrequent in
      cyclists, and its common origin is the external compressive aggression. In our
      patient we speculate and discuss that this radicular lesion could present
      different pathogenic mechanisms: the elongation, the compression and the
      secondary vasanervorum ischemia. In our knowledge S1 radiculopathy related to
      compressive lesions in sportsmen has not been previously described.

PMID- 15981688
TI  - Predictors of one-year seizure remission--a clinicoradiological and
      electroencephalographic study.
AB  - BACKGROUND AND AIMS: In epileptic patients, the requirement of number of
      antiepileptic drug (AED) to achieve seizure remission may be different in
      different geographic location and races. This study aims at evaluating the
      requirement of AEDs for one-year seizure remission of Indian epileptic patients
      and their predictors with special reference to ring enhancing lesion. SUBJECTS
      AND METHODS: Consecutive epileptic patients from neurology out patients
      department of a tertiary care center were included who completed one year follow
      up. Children < 12 years of age were excluded. A detailed history, neurological
      examination, CT scan and EEG were carried out. Patients were classified into
      idiopathic, symptomatic and cryptogenic epilepsy. Symptomatic epilepsies were
      further classified into patients with ring lesion and without it. Patients were
      prescribed appropriate AEDs, initially monotherapy then duo and later even more
      than 2 AEDs if seizures were not controlled. The relationship of various
      clinical, radiological and EEG changes with requirement of number of AEDs for
      seizure remission was compared employing Chi square test. RESULTS: There were 120
      patients whose mean age was 26.8 (13-71) years and 34 females. 48(40%) patients
      were classified into idiopathic, 53(44%) symptomatic and 19(15.80%) cryptogenic.
      After commencement of AEDs, 90(75%) patients were seizure free at 1 year; 78(65%)
      on monotherapy, 12(10%) on duotherapy and none on more than 2 drugs. The
      frequency of remission was higher in idiopathic (79%) and symptomatic (79%)
      compared to cryptogenic (52%). The seizure remission and requirement of number of
      AEDs were related to type of epilepsy, seizure frequency, neurological deficit
      and EEG abnormality. Symptomatic patients in non-ring lesion group were younger,
      had more frequent seizure, neurological deficit and EEG abnormality than ring
      lesion. Seizure remission was better in patients with ring lesion (87%) compared
      to without it (44%). CONCLUSION: 75% epileptic patients had one year seizure
      remission; majority achieved on monotherapy, occasionally on duotherapy and none
      on more than 2 AEDs. Symptomatic epilepsy due to ring lesion had higher seizure
      remission rate followed by idiopathic. Cryptogenic epilepsy, frequent seizure,
      neurological deficit and EEG abnormalities were related to poor remission and
      requirement of more number of AEDs.

PMID- 15981689
TI  - Electromyographic fatigue threshold of the biceps brachii muscle during dynamic
      contraction.
AB  - The purpose of this study was to identify the Electromyographic Fatigue Threshold
      (EMGFT) of the biceps brachii muscle bilaterally during the elbow flexion in
      tests performed in different times. 30 second test, 1 minute test and fatiguing
      test, in concentric (CC) and eccentric (EC) phases. Nine healthy young men
      performed the elbow flexion with loads corresponding at 25%, 35% and 45% of the
      one repetition maximum (1-RM) in separate days. The results indicated that the
      test applied for the biceps brachii muscle during elbow flexion induced a
      progressive increment of EMG activity with time indicating muscle fatigue and
      allowed the identification of the EMGFT. The three tests presented no difference
      of EMGFT between CC and EC phases bilaterally.

PMID- 15981690
TI  - Clinical and surface EMG characteristics of valproate induced tremors.
AB  - PURPOSE: To describe the Clinical and Surface EMG characteristics of Valproate
      induced Tremors. Sodium Valproate is known to produce tremors as a side effect.
      We analyzed clinical and surface electromyographic characteristics of tremors in
      epileptic subjects who presented with tremors while on sodium valproate. METHODS:
      Neurological examination and surface electromyographic recordings were performed
      on 20 subjects with sodium valproate induced tremors. Surface electromyographic
      tremerogram was correlated with clinical presentation of tremors. RESULTS: This
      study revealed sodium valproate induced tremors involving primarily upper limbs
      symmetrically. In the present study, all patients presented with action postural
      tremors except two, who had tremors in the resting position as well. None of
      these patients had tremors in goal-directed position. The tremors typically were
      of high frequency (mean 10 Hz), low amplitude, short burst duration and
      synchronous burst pattern (Synchronous EMG activity in the agonist and
      antagonistic muscles). CONCLUSIONS: Frequency, amplitude, burst duration and
      burst pattern of sodium valproate induced tremors resembles benign essential
      tremors on surface electromyographic recordings.

PMID- 15981691
TI  - The effect of the Schwartz-Jampel syndrome on masticatory and facial musculatures
      -an electromyographic analysis.
AB  - This study had the goal to perform an electromyography evaluation of the
      orbicularis oris, orbicularis oculi, masseter, and temporal muscles of two
      siblings with Schwartz-Jampel syndrome (SJS), in different clinical activities,
      comparing them to healthy controls (C). The Schwartz-Jampel syndrome is a rare
      genetic disorder (71 cases reported in worldwide literature), in which myotonia
      may be observed in the facial muscles, determining a standard facie that shows an
      appearance of someone who is sad and weeping For the electromyography (EMG), a
      Myotronics--K61 electromyographer, was used, with superficial and disposable
      silver chloride electrodes. By means of the analysis of the obtained results, we
      observed significant statistical differences for the masseter muscle and for
      orbicularis oculi muscles (p < 0.01) among the studied groups, in which the
      individuals with SJS presented greater muscular activity than the normal ones,
      used as healthy controls. The statistical difference between the two groups was
      not significant for the temporal muscle, as well as for the orbicularis oris
      muscle, although the EMG averages were much greater in patients who were bringers
      of the syndrome. This high muscular activity may be related to the facial osseous
      alterations, evidenced in both patients with SJS, such as the mandibular
      migrognathia, with an atrophy of the mandibular cortex and a consequent
      approximation between the inferior dental root apices and the mandible base, as
      well as the presence of hypoplastic condyles in terms of size and height.

PMID- 15981692
TI  - [Research methods in dentistry 10. Assessment of orthodontic treatment need].
AB  - Approximately one third of the Dutch population has an objective need for
      orthodontic treatment. Yet, patients mostly seek treatment because of aesthetic
      reasons. Recent social developments and the increased attention for aesthetics
      ask for ways to objectively measure treatment need. This is not only important
      because of the risks of orthodontic treatment, but also because of financial
      reasons. In this article indices to verify treatment need, i.e. the Index for
      Orthodontic Treatment Need (IOTN), de Dental Aesthetic Index (DAI) en de Index of
      Complexity, Outcome and Need (ICON), are discussed. All three indices seem to
      lead to a reduction of treatment need, especially in borderline cases. They can
      serve as 'neutral' instruments to discuss treatment need with patients and as
      instruments to allocate financial resources for orthodontic care.

PMID- 15981693
TI  - [Use of bone grafts from the mandibular body in pre-implant surgery].
AB  - Thirteen patients with resorption of the alveolar process in the upper or lower
      jaw were treated with augmentation using autogenous bone from the mandibular
      body. The objective and subjective results were retrospectively assessed. The
      morbidity of the donorsite was considered mild. 3 Patients experienced temporary
      sensory disturbance of the inferior alveolar nerve. In 1 patient spontaneous
      sequestration of a part of the transplant occured. In all patients the bonevolume
      at time of implantation was sufficient to insert the planned amount of implants.
      In total 46 implants were inserted. One implant was lost during follow-up and
      replaced. From this study it is concluded that the mandibular body can be
      considered as a good donor site for autogenous bone for pre-implant
      reconstruction of the alveolar process.

PMID- 15981694
TI  - [The practice guideline 'Treatment of tobacco addiction'].
AB  - The practice guidelines 'Treatment of tobacco dependence' are drawn up by
      collaboration of all medical and paramedical professional associations and aim at
      assisting patients who would like to quit smoking. The dental team has a barrier
      free opportunity to discuss smoking habits. The relation between smoking and oral
      health is quite obvious. Dental practitioners should ask about smoking habits
      regularly and smokers should be advised at least once a year to stop smoking.
      More intensive strategies for treatment of tobacco addiction in dental settings
      will be developed in the near future.

PMID- 15981695
TI  - [Spotlight on light].
AB  - An adequate perception is essential for a dentist because details are often just
      or just not visible. A proper use of light in the oral cavity (mouth of the
      patient), around the mouth and in the rest of the oral surgery, together with the
      use of light colours ought to make possible an optimal perception and colour
      matching. This can also prevent tiring adaptation of the eyes to too strong
      varying levels of light. Principles of a proper use of light and colours are
      described.

PMID- 15981696
TI  - [Trigeminal neuralgia by an acoustic neuroma. The need of imaging].
AB  - In a 43-year old female with neuralgia of the second and third branch of the
      trigeminal nerve, the diagnosis was made on the basis of clinical findings. After
      the patient was treated with 2 x 200 mg of carbamazepine, all initial symptoms
      resolved, which confirmed the diagnosis. To distinguish between idiopathic and
      secondary trigeminal neuralgia, magnetic resonance imaging was scheduled. This
      investigation showed an acoustic neuroma in the cerebellopontine angle. Without
      magnetic resonance imaging this benign tumour would be diagnosed in a much later
      stage and the patient would have suffered unnecessary co-morbidity. Due to the
      relatively high incidence of secondary trigeminal neuralgia, routine magnetic
      resonance imaging in patients with a trigeminal neuralgia is justifiable.

PMID- 15981697
TI  - Susceptibility testing of Pseudomonas aeruginosa by the Vitek 2 system: a
      comparison with Etest results.
AB  - P. aeruginona infections need accurate antimicrobial susceptibility data, as
      treatment mainly relies on antibiotic efficiency in debilitated patients. Vitek
      2, a popular automated susceptibility testing method, was compared with Etest to
      assess its reliability on 150 Belgian P. aeruginonas isolates. Vitek 2 and Etest
      exhibited a high degree of concordance, but some discrepancies in clinical
      category were evident for cefepime (high minor and borderline very major error
      rate) and for piperacillin/tazobactam (high very major error rate). Vitek 2
      appears to yield valuable information to the clinician concerning the
      antimicrobials amikacin, ceftazidime, ciprofloxacin and meropenem, in the setting
      of pseudomonas infection. For cefepime and piperacillin/tazobactam, a
      confirmatory testing by means of disk diffusion is worth considering.

PMID- 15981698
TI  - Bilateral blindness after starting highly active antiretroviral treatment in a
      patient with HIV infection and cryptococcal meningitis.
AB  - A 26-year-old HIV-seropositive Caucasian man with cryptococcal meningitis
      developed permanent bilateral blindness shortly after starting highly active
      antiretroviral treatment. The blindness may have been a consequence of an immune
      reactivation inflammatory syndrome caused by this treatment.

PMID- 15981699
TI  - A typical case of Sezary syndrome mimicking an eczema.
AB  - An 87-year-old woman was admitted with buccal pain that had started a few weeks
      before. She had been treated with topical steroids and antihistamines for an
      undetermined skin disease characterised by generalized erythroderma associated
      with pruritus for years. Her total white cell count was 13,290/mm3 with 19 %
      Sezary cells among the lymphocytes. Skin biopsy showed an infiltrate of
      inflammatory cells forming a dense band below the epidermis characterised by the
      presence of atypical lymphoid cells with large convoluted nuclei, and significant
      epidermotropism. Immunophenotyping studies in peripheral blood identified a large
      increase in CD4+ cells; CD7- T cells. Clonal T- cell receptor gamma gene
      rearrangement was detected on skin biopsy and bone marrow and on the skin biopsy
      with the PCR method. This case illustrates the misleading skin presentation of
      the Sezary syndrome in the elderly.

PMID- 15981700
TI  - Diagnosis and treatment of an unusual cause of sepsis in a diabetic patient: a
      Fournier's gangrene.
AB  - Actually, the Fournier's gangrene is described as a dermohypodermitis of the
      perineal, genital and/or perianal regions which can affect both sexes and a wide
      range of ages. The diagnosis of the disease is essentially made on clinical
      grounds. Imagery can be interesting in case of an intra-abdominal suspected
      source of the infection, uncertain diagnosis and good available trechniques.
      Surgery is the only potential curative therapy and the delay between its
      application and the beginning of the symptoms is the most predictive prognostic
      factor. Adjuvant treatments consist of broad spectrum antibiotherapy, hyperbaric
      oxygenotherapy and topical treatments have been proposed in order to improve the
      prognosis of these patients, which has remained relatively dark and unchanged for
      thirty years. The efficiency of such therapeutics are difficult to assess because
      all available studies do not meet the classical criteria of evidence-based
      medicine.

PMID- 15981701
TI  - Localised plasma-cell type Castleman's disease and AA-amyloidosis cured by
      resection. A case report and review of the literature.
AB  - Castleman's disease (CD) is a rare atypical lymphoproliferative disorder with
      frequent, yet less well known renal involvement. We describe the case of a 58
      year-old woman with localised abdominal plasma-cell type CD complicated by
      nephrotic syndrome due to renal amyloidosis. 18Fluorodeoxyglucose (FDG) positron
      emission tomography (PET) confirmed the unicentric nature. Resection of the mass
      resulted in regression of the signs of inflammation, a negative FDG-PET and
      complete remission of the nephrotic syndrome. A review of the literature of renal
      involvement (incidence, clinical and pathological manifestations, treatment and
      prognosis) in CD is provided.

PMID- 15981702
TI  - A case of multiple amoebic liver abscesses: clinical improvement after
      percutaneous aspiration.
AB  - Amoebic liver abscesses are by far the most common extra-intestinal manifestation
      of invasive amoebiasis. The classical clinical picture consists of fever, right
      upper quadrant pain and hepatomegaly. Ultrasound and serology make an early
      diagnosis possible. Amoebic liver abscesses usually appear singly and are
      normally situated in the right lobe of the liver. This case report refers to a
      white Belgian woman, living in an endemic area for amoebiasis, presenting with 25
      amoebic liver abscesses, who did not improve clinically despite appropriate anti
      amoebic therapy, is described. Only percutaneous drainage of the larger abscesses
      led to clinical recovery. Amoebic abscess aspiration and evacuation under
      ultrasonographic guidance is of limited risk, but in experienced hands may
      enhance clinical recovery, particularly in patients with large abscesses not
      responding to conservative medical treatment. Aspiration of large abscesses (> 5
      cm) is rarely necessary but should be considered if there is no clinical
      improvement after 3 days of nitroimidazole treatment with amoebicides.

PMID- 15981703
TI  - Long-term use of silver containing nose-drops resulting in systemic argyria.
AB  - Generalized argyria is a silver intoxication that results in pigmentation due to
      deposition of silver in the skin and mucous membranes. Compared to several
      decades ago, argyria is now relatively rare. We report a case of generalized
      argyria after continous use of argyrophedrine nosedrops in the last ten years.
      Argyria should be taken into consideration when a patient presents with a blue
      grey discoloration of the skin, particulary in areas exposed to the sun.

PMID- 15981704
TI  - About an unusual systemic disorder: report of a cryptic miliary tuberculosis.
AB  - We report here the case of a young Chinese woman with cryptic miliary
      tuberculosis associated with acute hepatitis, pancytopenia, biological
      disseminated intravascular coagulation (DIC), and hyponatremia. Following the
      introduction of a classic tuberculostatic treatment, her general status quickly
      improved. After an extensive review of the literature, this is, to the best of
      our knowledge, the first case of cryptogenic miliary tuberculosis with all its
      cumulative complications.

PMID- 15981705
TI  - Literacy as a leisure activity: free-time preferences of older children and young
      adolescents.
AB  - PURPOSE: Literacy plays an important role in the development of language in
      school-age children and adolescents. For example, by reading a variety of books,
      magazines, and newspapers, students gain exposure to complex vocabulary, and
      reading becomes a prime opportunity for learning new words. Despite the
      importance of reading for lexical development, little is known about the pleasure
      reading habits of today's youth. The first goal of this investigation was to
      examine the preferences of older children and young adolescents with respect to
      reading as a leisure-time activity and its relationship to other free-time
      options that are likely to compete for their attention. The second goal was to
      examine the amount of time that young people spend reading for pleasure each day
      and the types of materials they most enjoy reading. The third goal was to
      determine if preferences for free-time activities and reading materials would
      evince age- and gender-related differences during the period of development from
      late childhood through early adolescence (ages 11-15 years). The findings could
      serve as a reference point for understanding what is reasonable to expect of
      students during this age range. METHOD: The participants were 100 sixth graders
      (mean age = 11;7 [years; months]) and 100 ninth graders (mean age = 14;8)
      attending public schools in western Oregon. Each group contained an equal number
      of boys and girls, all of whom spoke English as their primary language and were
      considered to be typical achievers. All participants completed a survey
      concerning their preferred free-time activities and reading materials. They also
      reported the average amount of time they spent reading for pleasure each day.
      RESULTS: The most popular free-time activities were listening to music/going to
      concerts, watching television or videos, playing sports, and playing computer or
      video games. Least preferred activities were cooking, running or walking,
      writing, and arts and crafts. Reading was moderately popular. The most popular
      reading materials were magazines, novels, and comics; least popular were plays,
      technical books, and newspapers. Interest in pleasure reading declined during
      this age range (11-15 years), and boys were more likely than girls to report that
      they spent no time reading for pleasure. CLINICAL IMPLICATIONS: Given the
      importance of reading to lexical development in school-age children and
      adolescents, reading should be promoted as a leisure activity during these years.
      School-based speech-language pathologists (SLPs), in their role as language
      consultants, can benefit from understanding the pleasure-reading patterns of
      today's youth. It is especially important for SLPs to monitor these patterns in
      students who have language disorders, as it is common for these young people to
      experience deficits in reading and in lexical development. Fortunately, much can
      be done in school settings to encourage strong literacy habits in all students if
      SLPs work collaboratively with teachers, principals, psychologists, librarians,
      parents, and students. Suggestions are offered for ways to encourage young people
      to spend more time reading for pleasure.

PMID- 15981706
TI  - Diagnostic accuracy of the structured photographic expressive language test:
      third edition (SPELT-3).
AB  - PURPOSE: This study examined the empirical evidence for using the Structured
      Photographic Expressive Language Test: Third Edition (SPELT-3; Dawson, Stout, &
      Eyer, 2003) to diagnose language impairment in preschool children. The SPELT-3 is
      a revision of the SPELT-II (Werner & Kresheck, 1983), which has been proven in
      the past to have high levels of discriminant accuracy in identifying preschoolers
      with language impairment. METHOD: Forty-two 4- and 5-year-old children with a
      specific language impairment (SLI) and 43 children with typically developing (TD)
      language abilities were studied to determine the classification accuracy and
      other aspects of validity for the SPELT-3. RESULTS: Results from both an
      exploratory and a confirmatory sample indicated 90% sensitivity and 100%
      specificity when a cutoff standard score of 95 was applied to the data. In
      addition, use of the SPELT-3 was supported by additional data on convergent and
      divergent aspects of validity. IMPLICATIONS: The data provide empirical support
      for the use of the SPELT-3 for the purpose of differentiating between children
      with normal language and those with impaired language.

PMID- 15981707
TI  - Comprehension of third person singular /s/ in AAE-speaking children.
AB  - PURPOSE: This investigation examined the comprehension of third person singular
      /s/ in 30 African American English (AAE)-speaking children as a subject-number
      agreement marker on a comprehension task. METHOD: A comprehension task was
      presented to 30 typically developing AAE-speaking children between the ages of 4
      and 6. The children were randomly assigned to 1 of 2 groups to hear prerecorded
      counterbalanced stimuli. The comprehension task was designed to mask plurality of
      subject; therefore, the children had to focus on the verb as an indicator of
      subject number. RESULTS: Repeated measure analysis revealed that AAE-speaking
      children in this investigation did not understand third person singular /s/ as a
      number agreement marker. An additional analysis, d' (pronounced "d prime"),
      indicated that the AAE-speaking children are not sensitive to the third person
      singular /s/ as a clue to subject number. CLINICAL IMPLICATIONS: The inclusion of
      comprehension tasks of third person singular /s/ to help diagnose language
      impairment in this population may be problematic.

PMID- 15981708
TI  - Persuasive writing in children, adolescents, and adults: a study of syntactic,
      semantic, and pragmatic development.
AB  - PURPOSE: Persuasive writing is a demanding task that requires the use of complex
      language to analyze, discuss, and resolve controversies in a way that is clear,
      convincing, and considerate of diverse points of view. This investigation
      examined selected aspects of later language development in the context of
      persuasive writing. The purpose of the study was to obtain current information
      that could be used to design collaborative instruction involving speech-language
      pathologists and classroom teachers. In schools today, these professionals often
      work closely together to facilitate students' language development, including
      their ability to write persuasively. METHOD: Persuasive writing was investigated
      in typically developing children, adolescents, and adults (N = 180) whose mean
      ages were 11, 17, and 24 years, respectively. Each participant wrote an essay on
      the controversial topic of animals being trained to perform in circuses.
      Following this, the essays were examined in detail, focusing on selected aspects
      of syntactic, semantic, and pragmatic development. RESULTS: Performance improved
      in each of these domains during the years between childhood and adulthood. Age
      related changes included gradual increases in essay length; mean length of
      utterance; relative clause production; and the use of literate words, including
      adverbial conjuncts (e.g., typically, however, finally), abstract nouns (e.g.,
      longevity, respect, kindness), and metalinguistic and metacognitive verbs (e.g.,
      reflect, argue, disagree). In addition, older writers produced a greater number
      of different reasons in their essays and were more likely to acknowledge diverse
      points of view as compared to younger writers, thereby evidencing greater
      flexibility of thought. CLINICAL IMPLICATIONS: The study offers useful
      implications for speech-language pathologists and classroom teachers working
      together to improve students' persuasive writing skills. Suggestions are offered
      for ways to accomplish this by focusing on key aspects of later language
      development in the areas of syntax, semantics, and pragmatics.

PMID- 15981709
TI  - Preschool teachers' perceptions and reactions to challenging classroom behavior:
      implications for speech-language pathologists.
AB  - Awareness of issues of social competence and challenging behavior related to
      childhood language an communication disorders has been increasing. The purpose of
      this clinical exchange is to provide speech-language pathologists with basic
      information on communication disorders and challenging behaviors, as well as with
      insights into ways to support both students and classroom teachers. To provide
      effective services to children with language impairments and optimally support
      classroom staff, speech-language pathologists need to recognize (a) the
      interdependence of language, communication, social competence, and challenging
      behaviors; (b) the significance that challenging behaviors can have on
      evaluations of academic competency; and (c) how teachers in early childhood
      classrooms perceive and react to challenging behaviors. This clinical exchange
      provides an overview of the relationship between language, communication, and
      social competence, and presents preliminary survey research data investigating
      teachers' perceptions and reactions to challenging behaviors. Clinical
      implications are discussed, including considerations for intervention with
      children who may exhibit challenging behaviors in combination with language
      disabilities, and the speech-language pathologist's instrumental role in
      educating and supporting classroom staff to use communication strategies when
      managing challenging classroom behaviors.

PMID- 15981710
TI  - Clinicians deserve better: observations on a clinical forum titled "what child
      language research may contribute to the understanding and treatment of
      stuttering" (2004).

PMID- 15981711
TI  - Rafts as missing link between multidrug resistance and sphingolipid metabolism.

PMID- 15981713
TI  - A subsequent fit of time series and amplitude histogram of patch-clamp records
      reveals rate constants up to 1 per microsecond.
AB  - Fast gating in time series of patch-clamp current demands powerful tools to
      reveal the rate constants of the adequate Hidden Markov model. Here, two
      approaches are presented to improve the temporal resolution of the direct fit of
      the time series. First, the prediction algorithm is extended to include
      intermediate currents between the nominal levels as caused by the anti-aliasing
      filter. This approach can reveal rate constants that are about 4 times higher
      than the corner frequency of the anti-aliasing filter. However, this approach is
      restricted to time series with very low noise. Second, the direct fit of the time
      series is combined with a beta fit, i.e., a fit of the deviations of the
      amplitude histogram from the Gaussian distribution. Since the "theoretical"
      amplitude histograms for higher-order Bessel filters cannot be calculated by
      analytical tools, they are generated from simulated time series. In a first
      approach, a simultaneous fit of the time series and of the Beta fit is tested.
      This simultaneous fit, however, inherits the drawbacks of both approaches, not
      the benefits. More successful is a subsequent fit: The fit of the time series
      yields a set of rate constants. The subsequent Beta fit uses the slow rate
      constants of the fit of the time series as fixed parameters and the optimization
      algorithm is restricted to the fast ones. The efficiency of this approach is
      illustrated by means of time series obtained from simulation and from the
      dominant K+ channel in Chara. This shows that temporal resolution can reach the
      microsecond range.

PMID- 15981714
TI  - Monitoring Cl- movement in single cells exposed to hypotonic solution.
AB  - Self-referencing ion--selective electrodes (ISEs), made with Chloride Ionophore I
      Cocktail A (Fluka), were positioned 1-3 microm from human embryonic kidney cells
      (tsA201a) and used to record chloride flux during a sustained hyposmotic
      challenge. The ISE response was close to Nernstian when comparing potentials (VN)
      measured in 100 and 10 mM NaCl (deltaVN = 57 +/- 2 mV), but was slightly greater
      than ideal when comparing 1 and 10 mM NaCl (deltaVN = 70 +/- 3 mV). The response
      was also linear in the presence of 1 mM glutamate, gluconate, or acetate, 10
      microM tamoxifen, or 0.1, 1, or 10 mM HEPES at pH 7.0. The ISE was approximately
      3 orders of magnitude more selective for Cl- over glutamate or gluconate but less
      than 2 orders of magnitude move selective for Clover bicarbonate, acetate,
      citrate or thiosulfate. As a result this ISE is best described as an anion
      sensor. The ISE was 'poisoned' by 50 microM 5-nitro-2-(3phenylpropyl-amino)
      benzoic acid (NPPB), but not by tamoxifen. An outward anion efflux was recorded
      from cells challenged with hypotonic (250 +/- 5 mOsm) solution. The increase in
      efflux peaked 7-8 min before decreasing, consistent with regulatory volume
      decreases observed in separate experiments using a similar osmotic protocol. This
      anion efflux was blocked by 10 microM tamoxifen. These results establish the
      feasibility of using the modulation of electrochemical, anion-selective,
      electrodes to monitor anions and, in this case, chloride movement during volume
      regulatory events. The approach provides a real-time measure of anion movement
      during regulated volume decrease at the single-cell level.

PMID- 15981712
TI  - Novel properties of a mouse gamma-aminobutyric acid transporter (GAT4).
AB  - We expressed the mouse gamma-aminobutyric acid (GABA) transporter GAT4
      (homologous to rat/ human GAT-3) in Xenopus laevis oocytes and examined its
      functional and pharmacological properties by using electrophysiological and
      tracer uptake methods. In the coupled mode of transport (Na+/ Cl-/GABA
      cotransport), there was tight coupling between charge flux and GABA flux across
      the plasma membrane (2 charges/GABA). Transport was highly temperature-dependent
      with a temperature coefficient (Q10) of 4.3. The GAT4 turnover rate (1.5 s(-l); 
      50 mV, 21 degrees C) and temperature dependence suggest physiological turnover
      rates of 15-20 s(-1). No uncoupled current was observed in the presence of Na+.
      In the absence of external Na+, GAT4 exhibited two distinct uncoupled currents.
      (i) A Cl- leak current (ICl(leak)) was observed when Na+ was replaced with
      choline or tetraethylammonium. The reversal potential of (ICl(leak)) followed the
      Cl- Nernst potential. (ii) A Li+ leak current (ILi(leak)) was observed when Na+
      was replaced with Li+. Both leak currents were inhibited by Na+, and both were
      temperature-independent (Q10 approximately 1). The two leak modes appeared not to
      coexist, as Li+ inhibited (ICl(leak)). The results suggest the existence of
      cation- and anion-selective channel-like pathways in GAT4. Flufenamic acid
      inhibited GAT4 Na+/Cl-/GABA cotransport, ILi(leak), and ICl(leak), (Ki
      approximately 30 microM), and the voltage-induced presteady-state charge
      movements (Ki approximately 440 microM). Flufenamic acid exhibited little or no
      selectivity for GAT1, GAT2, or GAT3. Sodium and GABA concentration jicroumps
      revealed that slow Na+ binding to the transporter is followed by rapid GABA
      induced translocation of the ligands across the plasma membrane. Thus, Na+
      binding and associated conformational changes constitute the rate-limiting steps
      in the transport cycle.

PMID- 15981715
TI  - Musculoskeletal radiology.

PMID- 15981716
TI  - Colon dissection: a new three-dimensional reconstruction tool for computed
      tomography colonography.
AB  - PURPOSE: To improve the sensitivity of computed tomography (CT) colonography in
      the detection of polyps by comparing the 3D reconstruction tool "colon
      dissection" and endoluminal view (virtual colonoscopy) with axial 2D
      reconstructions. MATERIAL AND METHODS: Forty-eight patients (22 M, 26 F, mean age
      57 +/- 21) were studied after intra-anal air insufflation in the supine and prone
      positions using a 16-slice helical CT (16 x 0.625 mm, pitch 1.7; detector
      rotation time 0.5 s; 160 mAs und 120 kV) and conventional colonoscopy. Two
      radiologists blinded to the results of the conventional colonoscopy analyzed the
      3D reconstruction in virtual-endoscopy mode, in colon-dissection mode, and axial
      2D slices. RESULTS: Conventional colonoscopy revealed a total of 35 polyps in 15
      patients; 33 polyps were disclosed by CT methods. Sensitivity and specificity for
      detecting colon polyps were 94% and 94%, respectively, when using the "colon
      dissection", 89% and 94% when using "virtual endoscopy", and 62% and 100% when
      using axial 2D reconstruction. Sensitivity in relation to the diameter of colon
      polyps with "colon dissection", "virtual colonoscopy", and axial 2D-slices was:
      polyps with a diameter >5.0 mm, 100%, 100%, and 71%, respectively; polyps with a
      diameter of between 3 and 4.9 mm, 92%, 85%, and 46%; and polyps with a diameter <
      3 mm, 89%, 78%, and 56%. The difference between "virtual endoscopy" and "colon
      dissection" in diagnosing polyps up to 4.9 mm in diameter was statistically
      significant. CONCLUSION: 3D reconstruction software "colon dissection" improves
      sensitivity of CT colonography compared with the endoluminal view.

PMID- 15981717
TI  - Morphological imaging in the localization of neuroendocrine
      gastroenteropancreatic tumors found by somatostatin receptor scintigraphy.
AB  - PURPOSE: To evaluate the necessity of morphological images (MI) in reading
      somatostatin receptor scintigraphy (SRS) in patients with suspected
      neuroendocrine gastroenteropancreatic (GEP) tumors. MATERIAL AND METHODS: A
      Japanese multicenter clinical trial of SRS was conducted in 40 patients with
      suspected GEP tumors. Three experienced radiologists interpreted the images in
      three separate sessions in a blinded manner (1: SRS images alone, 2: MI alone, 3:
      SRS and MI analyzed simultaneously), and the reading results of each session were
      compared. In addition, the diagnostic abilities of SRS, MI and SRS alone and
      simultaneous SRS and MI readings were compared for patients where final diagnosis
      was obtained. RESULTS: SRS detected more suspected lesions (positive or
      inconclusive uptake) than morphological images did (51 vs 27 lesions), but
      included many physiological uptakes detected as positive or inconclusive uptakes.
      Combined reading of SRS and morphological images helped to correctly recognize
      these physiological uptakes, and also helped in determining the anatomical
      localization of the abnormal uptakes. Combined reading of SRS and morphological
      images gave the highest diagnostic impact. CONCLUSION: The sensitivity of SRS
      with regard to GEP is high. However the specificity is very low. Morphologic
      imaging is necessary for the exclusion of physiological uptake and correct
      anatomic location of an abnormal tracer uptake. The combined reading of SRS and
      morphologic imaging studies gives the highest diagnostic impact.

PMID- 15981719
TI  - Detection of mild emphysema by computed tomography density measurements.
AB  - PURPOSE: To assess the ability of a conventional density mask method to detect
      mild emphysema by high-resolution computed tomography (HRCT); to analyze factors
      influencing quantification of mild emphysema; and to validate a new algorithm for
      detection of mild emphysema. MATERIAL AND METHODS: Fifty-five healthy male
      smokers and 34 never-smokers, 61-62 years of age, were examined. Emphysema was
      evaluated visually, by the conventional density mask method, and by a new
      algorithm compensating for the effects of gravity and artifacts due to motion and
      the reconstruction algorithm. Effects of the reconstruction algorithm, slice
      thickness, and various threshold levels on the outcome of the density mask area
      were evaluated. RESULTS: Forty-nine percent of the smokers had mild emphysema.
      The density mask area was higher the thinner the slice irrespective of the
      reconstruction algorithm and threshold level. The sharp algorithm resulted in
      increased density mask area. The new reconstruction algorithm could discriminate
      between smokers with and those without mild emphysema, whereas the density mask
      method could not. The diagnostic ability of the new algorithm was dependent on
      lung level. At about 90% specificity, sensitivity was 65-100% in the apical
      levels, but low in the rest of the lung. CONCLUSION: The conventional density
      mask method is inadequate for detecting mild emphysema, while the new algorithm
      improves the diagnostic ability but is nevertheless still imperfect.

PMID- 15981718
TI  - Reappraisal of left-sided gallbladder and its accompanying anomalies: a report of
      two cases and literature review.
AB  - We report two cases of coexistent left-sided gallbladder and right-sided
      ligamentum teres with portal vein anomalies documented by magnetic resonance
      imaging (MRI) and three-dimensional (3D) computed tomography during arterial
      portography (CTAP). Reformatted 3D MR and CTAP images provide an informative
      illustration of the accompanying portal vein anomalies. This important anatomical
      information is useful in preoperative work-up of hepatobiliary surgery.

PMID- 15981720
TI  - Intravascular malignant lymphomatosis: diffusion-weighted magnetic resonance
      imaging characteristics.
AB  - Intravascular malignant lymphomatosis is an unusual condition in which malignant
      lymphoma cells form microscopic masses within the blood vessels of the central
      nervous system. Occlusion of the involved blood vessels can lead to multifocal
      cerebral infarcts. Diffusion-weighted magnetic resonance imaging (MRI) reveals a
      subacute infarction pattern (bright high signal intensity on b = 1000 s/mm2
      images and intermediate apparent diffusion coefficient values) in the cerebral
      deep white matter. We present MRI findings of a 68-year-old woman with
      intravascular malignant lymphomatosis involving the cerebral white matter and the
      thoracic cord.

PMID- 15981721
TI  - Intra-arterial magnetic resonance angiography of the iliac arteries: clinical
      experience using two different protocols.
AB  - PURPOSE: To assess the feasibility of intra-arterial magnetic resonance
      angiography (iaMRA) with two different protocols. MATERIAL AND METHODS: Twenty
      patients were prospectively examined after digital subtraction angiography.
      Contrast-enhanced iaMRA was performed using a 1.5T magnetic resonance imaging
      (MRI) system. Contrast agent (gadodiamide) was injected through a conventional
      angiography catheter placed in the abdominal aorta. The patients were randomized
      into two groups each comprising 10 patients. Group 1 was examined with a FLASH-3D
      (fast low-angle shot) sequence, allowing the center of the k-space to be acquired
      0.5 s after initiation of the measurement. Group 2 was examined with the
      identical sequence, but the center of the k-space was acquired after 8.7 s. The
      increase in the intravascular signal intensity was determined and the diagnostic
      value of the angiograms was independently scored by 4 investigators using a 5
      point scale. RESULTS: Nineteen of 20 MRAs were scored as diagnostic; only 1 was
      scored as non-diagnostic by 2 observers. The diagnostic value of the angiograms
      of group 2 was judged superior to that of group 1 owing to a more homogeneous
      intravascular contrast distribution. CONCLUSION: Intra-arterial MRA is feasible.
      The diagnostic value of angiograms using a flash sequence with center of the k
      space acquisition after 8.7 s ranged from good to excellent. This sequence is
      appropriate for iaMRA of iliac arteries to support MR guided intervention.

PMID- 15981722
TI  - Percutaneous vertebroplasty: indications, contraindications, technique, and
      complications.
AB  - Percutaneous vertebroplasty is emerging as one of the most promising new
      interventional procedures for relieving (or reducing) painful vertebra, with the
      injection of surgical polymethylmethacrylate or cement into vertebral bodies.
      This imaged-guided technique, originally used to treat vertebral hemangioma, has
      recently been extended to the treatment of metastases, osteoporotic compression
      fractures, and vertebral myeloma. It is increasingly being accepted as a main
      treatment of choice in the management of resistant back pain due to vertebral
      compression fractures, especially in the elderly individual who is not a
      candidate for surgery. In this article, we review indications, contraindications,
      technique, and complications of percutaneous vertebroplasty.

PMID- 15981723
TI  - Effect of spinal degenerative changes on volumetric bone mineral density of the
      central skeleton as measured by quantitative computed tomography.
AB  - PURPOSE: To evaluate the impact of degenerative changes due to osteoarthritis
      (OA) at the spine on volumetric bone mineral density (BMD) as measured by
      volumetric quantitative computed tomography (vQCT). MATERIAL AND METHODS: Eighty
      four elderly women (mean age 73 +/- 6 years), comprising 33 with vertebral
      fractures assessed by radiographs and 51 without vertebral fractures, were
      studied. Trabecular, cortical, and integral BMD were examined at the spine and
      hip using a helical CT scanner and were compared to dual X-ray absorptiometry
      (DXA) measurements at the same sites. OA changes visible on the radiographs were
      categorized into two grades according to severity. Differences in BMD measures
      obtained in the two groups of patients defined by OA grade using the described
      radiologic methods were compared using analysis of variance. Standardized
      difference (effect sizes) was also compared between radiologic methods. RESULTS:
      Spinal trabecular BMD did not differ significantly between OA grade 0 and OA
      grade 1. Spinal cortical and integral BMD measures showed statistically
      significant differences, as did the lumbar spine DXA BMD measurement (13%, P =
      0.02). The QCT measurements at the hip were also higher in OA 1 subjects. Femoral
      trabecular BMD was 13-15% higher in OA grade 1 subjects than in OA grade 0
      subjects. The cortical BMD measures in the CT_TOT_FEM and CT_TROCH ROI's were
      also higher in the OA 1 subjects. The integral QCT BMD measures in the hip showed
      difference between grades OA 1 and 0. The DXA measurements in the neck and
      trochanter ROI's showed smaller differences (9 and 11%, respectively). There were
      no statistically significant differences in bone size. CONCLUSION: There is no
      evidence supporting that trabecular BMD measurements by QCT are influenced by OA.
      Instead, degenerative changes have an effect on both cortical and integral QCT,
      and on DXA at the lumbar spine and the hip. For subjects with established OA,
      assessment of BMD by volumetric QCT may be suggested.

PMID- 15981724
TI  - Percutaneous vertebroplasty for compression fracture: analysis of vertebral body
      volume by CT volumetry.
AB  - PURPOSE: To evaluate the relationships between volume of vertebral bodies with
      compression fracture (measured by CT volumetry) before percutaneous
      vertebroplasty, the amount of bone cement injected, and the effect of treatment.
      MATERIAL AND METHODS: We examined 49 consecutive patients, with 104 vertebral
      body compression fractures, who underwent percutaneous injection of bone cement.
      Vertebral body volume was measured by CT volumetry. The patient's pain level was
      assessed using a visual analog scale (VAS) before and after the procedure.
      Improvement in VAS was defined as the decrease in VAS after the procedure.
      Relationships between vertebral body volume, the amount of bone cement, and the
      effect of treatment were evaluated using Pearson's correlation coefficient test.
      RESULTS: Average vertebral body volume was 26.3 +/- 8.1 cm3; average amount of
      bone cement was 3.2 +/- 1.1 ml; and average improvement in VAS was 4.9 +/- 2.7.
      The vertebral body volume was greater if a larger amount of bone cement was
      injected. There was a significant positive correlation between vertebral body
      volume and amount of bone cement (r = 0.44; P < 0.0001). However, there was no
      correlation between vertebral body volume and improvement in VAS, or between
      amount of bone cement and improvement in VAS. CONCLUSION: In percutaneous
      vertebroplasty for vertebral body compression fracture, there is a positive
      correlation between vertebral body volume and amount of bone cement, but
      improvement in VAS does not correlate with vertebral body volume or amount of
      bone cement.

PMID- 15981725
TI  - Extrapedicular approach of percutaneous vertebroplasty in the treatment of upper
      and mid-thoracic vertebral compression fracture.
AB  - PURPOSE: To evaluate the clinical outcome of the extrapedicular approach of
      percutaneous vertebroplasty (PVP) for upper and mid-thoracic vertebral
      compression fractures in patients. MATERIAL AND METHODS: Extrapedicular
      vertebroplasty was performed in painful compression fractures at T4-T8 levels.
      The assessment criteria were changes over time in visual analog scale (VAS) and
      mobility score. We evaluated the volume of cement injected, the size of needle
      required, and complications. RESULTS: Procedures were performed in 27 patients
      with a total of 34 affected vertebral bodies. Early (within a week) and one year
      later, clinical follow-ups showed that pain intensity had decreased by 50% one
      day after operation and later by 70-80%. Mobility scores of all patients were
      improved immediately after the procedure. Average volume of
      polymethylmethacrylate (PMMA) per vertebral body was 3.8 +/- 1.2 ml. Leakage of
      PMMA occurred in one vertebral level (intradiskal space), but did not cause
      clinical complications. CONCLUSION: PVP of upper and mid-thoracic spine with an
      extrapedicular approach is an efficient and safe procedure for treating painful
      thoracic vertebral compression fracture under a cautious patient selection and
      meticulous technical procedure.

PMID- 15981726
TI  - Cartilage metabolism in osteoarthritis and the influence of viscosupplementation
      and steroid: a review.
AB  - Osteoarthritis (O.A.) is the most common type of articular disease. This is an
      idiopathic joint disease characterized by an imbalance between synthesis and
      degradation of articular cartilage and subchondral bone accompanied by capsular
      fibrosis, osteophyte formation and variable grade of inflammation of synovial
      membrane. Joint lubrication is naturally provided by Hyaluronic acid in syovial
      fluid. Hyaluronan is present in abundance in normal young and healthy joints. In
      degenerative O.A. Hyaluronan is smaller in size, molecular weight and diminished
      in concentration. This decrease in joint lubrication and shock absorbing
      mechanism in O.A. can be remedied by intraarticular viscosupplementation.
      Alternatively the pain and secondary inflammation in O.A. can be relieved by
      intraarticular injection of steroids and long acting local anesthetics. Promt and
      effective reduction in local inflammation occurs after intra-articular injection
      of corticosteriod. This article reviews the cartilage metabolism in O.A.,
      discusses the pros and cons of these treatments and provides a literature review
      of the studies which compare benefits and adverse reactions of
      viscosupplementation vs. intraarticular steroids with placebo treatment.

PMID- 15981727
TI  - Posterolateral complex knee injuries: magnetic resonance imaging with surgical
      correlation.
AB  - PURPOSE: To describe the magnetic resonance imaging (MRI) findings of injuries of
      the posterolateral aspect of the knee and to evaluate the diagnostic capabilities
      of MRI in the assessment of these injuries. MATERIAL AND METHODS: The MRI studies
      of 14 patients (mean age 33 years) with trauma to the posterolateral aspect of
      the knee were retrospectively reviewed, and the imaging findings were correlated
      with those of surgery. RESULTS: In all patients, MRI showed an intact iliotibial
      (ITB) band. MRI showed injury to the biceps tendon in 11 (79%), the gastrocnemius
      tendon in 1 (7%)), the popliteus tendon in 5 (36%), and the lateral collateral
      ligament (LCL) in 14 (100%) patients. Tear of the anterior cruciate ligament
      (ACL) was seen in 11 (79%) patients and tear of the posterior cruciate ligament
      (PCL) in 4 (29%) patients. With routine MRI, visualization of the popliteofibular
      or fabellofibular ligaments was incomplete. On MRI, the lateral meniscus and the
      medial meniscus were torn with equal frequency (n = 4; 29%). Osteochondral
      defects were seen in 5 (36%) cases and joint effusion in all 14 (100%) cases on
      MRI. Using surgical findings as the standard for diagnosis, MRI proved 86%
      accurate in the detection of injury to the ITB band, the biceps tendon (93%), the
      gastrocnemius tendon (100%), the popliteus tendon (86%), the LCL (100%), the ACL
      (79%), the PCL (86%), the lateral meniscus (90%), the medial meniscus (82%), and
      the osteochondral structures (79%). Surgical correlation confirmed the MRI
      findings of joint effusion in all cases. CONCLUSION: MRI is well suited for
      demonstrating the presence and extent of injuries of the major structures of the
      posterolateral complex of the knee, allowing characterization of the severity of
      injury.

PMID- 15981728
TI  - High-resolution magnetic resonance imaging of trabecular bone in the wrist at 3
      tesla: initial results.
AB  - PURPOSE: To evaluate the feasibility of high-resolution magnetic resonance
      imaging (MRI) of trabecular bone of the wrist at 3 Tesla (3T) in vivo and to
      assess the potential benefit of the increased resolution for clinical assessment
      of structural changes in spongy bone. MATERIAL AND METHODS: High-resolution MRI
      of the wrist was performed with a whole-body 3T MR scanner using a dedicated
      circularly polarized transmit-receive wrist-coil. Two 3D-FISP sequences with a
      spatial resolution of 300 x 300 x 300 microm3 in a measuring time of TA = 7:51
      min, and 200 x 200 x 200 microm3 in TA = 9:33 min were applied. Seven young
      healthy volunteers and three elderly subjects with suspected osteoporosis were
      examined. The signal-to-noise ratio (SNR) in the optimized setup at 3T was
      compared to measurements at 1.5T. RESULTS: The images at 3T allow microscopic
      analysis of the bone structure at an isotropic spatial resolution of 200 microm
      in examination times of <10 min. Differences in the structure of the spongy bone
      between normal and markedly osteoporotic subjects are well depicted. The SNR at
      3T was found up to 16 times higher than at 1.5T applying unchanged imaging
      parameters. CONCLUSION: The proposed high-resolution MRI technique offers high
      potential in the diagnosis and follow-up of diseases with impaired bone structure
      of hand and/or wrist in clinical applications.

PMID- 15981729
TI  - Giant cavernous angioma of the temporal lobe: a case report and review of the
      literature.
AB  - Cavernous angiomas of the central nervous system are angiographically occult
      vascular lesions and are easily diagnosed by magnetic resonance imaging (MRI).
      Giant cavernous angiomas (GCA) are rare, with only 11 cases reported in the
      literature. Imaging appearance of GCAs has not been reviewed previously. We
      report a GCA of the temporal lobe, and discuss its computed tomography and MRI
      findings in the view of the literature. Imaging appearance of GCAs is variable.
      Some GCAs have features that are similar to those of typical cavernous angiomas,
      whereas some lesions may be purely cystic; and some present with significant
      contrast enhancement and mass effect, mimicking neoplasms. While the presence of
      hemosiderin, blood degradation products, and calcification may be helpful in the
      diagnosis of some cases, the correct diagnosis is not apparent until
      histopathological evaluation of the specimen is made in many instances.

PMID- 15981730
TI  - Prevalence study of proximal vertebral artery stenosis using high-resolution
      contrast-enhanced magnetic resonance angiography.
AB  - PURPOSE: To evaluate the prevalence of proximal vertebral artery stenosis,
      compared wiith those of the distal vertebral/basilar artery and extracranial
      internal carotid artery, in a large population of stroke and non-stroke patients.
      MATERIAL AND METHODS: Nine-hundred-and-thirty-five patients who underwent high
      resolution contrast-enhanced magnetic resonance angiography in a regional general
      hospital were categorized into six groups based on neurological symptoms and
      disease: an asymptomatic group (n = 182), a minor symptom group with headache or
      dizziness (n = 519), a cardiac group with coronary artery steno-occlusive disease
      (n = 15), a hemorrhagic group with old cerebral hemorrhage (n=26), an anterior
      circulation infarct group (n = 121), and posterior circulation infarct group (n =
      72). Prevalence of stenosis of the proximal vertebral artery, distal
      vertebral/basilar artery, and internal carotid artery was analyzed. RESULTS: The
      prevalence of stenosis of the proximal vertebral artery, distal vertebral/
      basilar artery, and internal carotid artery was 12.9%, 5.5%, and 7.2%,
      respectively, in the study population, and rose as the age increased (P < 0.0001
      for all arteries). The prevalence of stenosis of the proximal vertebral artery,
      distal vertebral/basilar artery, and internal carotid artery was 3.3%, 0.5%, and
      1.1%, respectively, in the asymptomatic group; 8.3%, 2.1%, and 3.7%,
      respectively, in the minor symptom group; 13.3%, 6.7% and 6.7%, respectively, in
      the cardiac group; 19.2%, 7.7%, and 7.7%, respectively, in the hemorrhagic group;
      27.3%, 8.3%, and 25.6%, respectively, in the anterior circulation infarct group;
      and 44.4%, 36.1%, and 16.7%, respectively, in the posterior circulation infarct
      group. This increasing tendency of stenosis accordingly was statistically
      significant (P < 0.0001 for all arteries). CONCLUSION: The prevalence of proximal
      vertebral artery stenosis was highest, compared with those of the distal
      vertebral/basilar artery and internal carotid artery, although the clinical
      significance of proximal vertebral artery stenosis should be investigated in
      further studies.

PMID- 15981731
TI  - Magnetic resonance imaging findings in chronic carbon monoxide intoxication.
AB  - PURPOSE: To define the cranial magnetic resonance imaging (MRI) features of the
      chronic stage of carbon monoxide (CO) poisoning in patients with and without
      neuropsychiatric sequelae. MATERIAL AND METHODS: Eight patients who had neither
      symptoms nor neurological sequelae and eight patients with neuropsychiatric
      sequelae were included in the study. Patients aged between 9 to 57 (mean 32.2
      years). All patients had been comatose at initial admittance and awoke after
      normobaric 100% oxygen therapy within 1-7 days. In this study, the patients were
      being examined with routine cranial MRI between 1 and 10 years (mean 3.4 years)
      after exposure to CO. RESULTS: The most common finding was bilateral symmetric
      hyperintensity of the white matter, which was more significant in the centrum
      semiovale, with relative sparing of the temporal lobes and anterior parts of the
      frontal lobes on T2-weighted and FLAIR images in all patients. Cerebral cortical
      atrophy was seen in 10 patients; mild atrophy of cerebellar hemispheres in 8; and
      vermian atrophy in 11. Corpus callosum was atrophic in one patient. Bilateral
      globus pallidus lesions were seen in three patients. The lesions were hypointense
      on T1-weighted images and hyperintense on T2-weighted and FLAIR images.
      CONCLUSION: Patients with severe CO intoxication may develop persistent cerebral
      changes independently of their neuropsychiatric findings in the chronic stage.
      They may present with characteristic MRI findings as described here, even if
      asymptomatic. The history of CO exposure is therefore helpful for recognizing and
      interpreting the MRI findings of chronic stage CO intoxication.

PMID- 15981732
TI  - Magnetic resonance imaging of the feto-placentar unit after fetoscopic laser
      coagulation for twin-to-twin transfusion syndrome.
AB  - Twin-to-twin transfusion syndrome (TTTS) is a severe complication in
      monochorionic twin pregnancies that results from a hemodynamical imbalance of
      placentar vascular anstomoses that connect the circulation of both fetuses. In
      TTTS, a poly/oligohydramnios sequence with high fetal morbidity and mortality
      rates occurs. Fetoscopic laser coagulation of the placentar anastomoses can limit
      or prevent fetal injury. The purpose of this report is to present and discuss
      fetal magnetic resonance imaging as a postoperative imaging tool after fetoscopic
      laser coagulation.

PMID- 15981733
TI  - Annual Review of Cosmetic Ingredient Safety Assessments--2002/2003.

PMID- 15981735
TI  - Distinguished service award, F. Peter Guengerich.

PMID- 15981734
TI  - Final report on the safety assessment of potassium silicate, sodium metasilicate,
      and sodium silicate.
AB  - Potassium Silicate, Sodium Metasilicate, and Sodium Silicate combine metal
      cations with silica to form inorganic salts used as corrosion inhibitors in
      cosmetics. Sodium Metasilicate also functions as a chelating agent and Sodium
      Silicate as a buffering and pH adjuster. Sodium Metasilicate is currently used in
      168 formulations at concentrations ranging from 13% to 18%. Sodium Silicate is
      currently used in 24 formulations at concentrations ranging from 0.3% to 55%.
      Potassium Silicate and Sodium Silicate have been reported as being used in
      industrial cleaners and detergents. Sodium Metasilicate is a GRAS (generally
      regarded as safe) food ingredient. Aqueous solutions of Sodium Silicate species
      are a part of a chemical continuum of silicates based on an equilibrium of
      alkali, water, and silica. pH determines the solubility of silica and, together
      with concentration, determines the degree of polymerization. Sodium Silicate
      administered orally is readily absorbed from the alimentary canal and excreted in
      the urine. The toxicity of these silicates has been related to the molar ratio of
      SiO2/Na2O and the concentration being used. The Sodium Metasilicate acute oral
      LD50 ranged from 847 mg/kg in male rats to 1349.3 mg/kg in female rats and from
      770 mg/kg in female mice to 820 mg/kg in male mice. Gross lesions of variable
      severity were found in the oral cavity, pharynx, esophagus, stomach, larynx,
      lungs, and kidneys of dogs receiving 0.25 g/kg or more of a commercial detergent
      containing Sodium Metasilicate; similar lesions were also seen in pigs
      administered the same detergent and dose. Male rats orally administered 464 mg/kg
      of a 20% solution containing either 2.0 or 2.4 to 1.0 ratio of sodium oxide
      showed no signs of toxicity, whereas doses of 1000 and 2150 mg/kg produced
      gasping, dypsnea, and acute depression. Dogs fed 2.4 g/kg/day of Sodium Silicate
      for 4 weeks had gross renal lesions but no impairment of renal function. Dermal
      irritation of Potassium Silicate, Sodium Metasilicate, and Sodium Silicate ranged
      from negligible to severe, depending on the species tested and the molar ratio
      and concentration tested. Sodium Metasilicate was negative in the local lymph
      node assay (LLNA), but a delayed-type hypersensitivity response was observed in
      mice. Potassium Silicate was nonirritating in two acute eye irritation studies in
      rabbits. Sodium Metasilicate (42.4% H2O) was corrosive to the rabbit eye. Sodium
      Silicate was a severe eye irritant in some eye irritation studies, but was
      irritating or nonirritating in others. A skin freshener containing Sodium
      Silicate was nonirritating. Sodium Metasilicate was nonmutagenic in bacterial
      cells. Rats given Sodium Silicate (600 and 1200 ppm of added silica) in the
      drinking water in reproductive studies produced a reduced number of offspring: to
      67% of controls at 600 ppm and to 80% of controls at 1200 ppm. Three adult rats
      injected intratesticularly and subcutaneously with 0.8 mM/kg of Sodium Silicate
      showed no morphological changes in the testes and no effect on the residual
      spermatozoa in the ductus deferens. Sodium Metasilicate (37% in a detergent)
      mixed with water was a severe skin irritant when tested on intact and abraded
      human skin, but 6%, 7%, and 13% Sodium Silicate were negligible skin irritants to
      intact and abraded human skin. Sodium Silicate (10% of a 40% aqueous solution)
      was negative in a repeat-insult predictive patch test in humans. The same aqueous
      solution of Sodium Silicate was considered a mild irritant under normal use
      conditions in a study of cumulative irritant properties. The Cosmetic Ingredient
      Review (CIR) Expert Panel recognized the irritation potential of these
      ingredients, especially in leave-on products. However, because these ingredients
      have limited dermal absorption and Sodium Metasilicate is a GRAS direct food
      substance, the Panel deemed the ingredients safe for use in cosmetic products in
      the practices of use and concentration described in this safety assessment, when
      formulated to avoid irritation.

PMID- 15981736
TI  - Life and times in biochemical toxicology.
AB  - The biochemical facets of toxicology have always had a major role in providing
      insight into mechanisms. Some of the history of the development of this area is
      summarized, including metabolism, enzymology, and the chemistry of reactive
      intermediates. Knowledge in these fields has had a major impact in the areas of
      drug metabolism and safety assessment, which are both critical steps in the
      development of pharmaceuticals and the rational use of commodity chemicals. The
      science of toxicology has developed considerably with input from other
      disciplines and today is poised to emerge as a predictive science with even more
      dramatic impact. The challenges ahead are considerable but there is renewed
      excitement in the potential of the field. As in the past, further advances in the
      field of toxicology will require the input of knowledge from many disciplines.

PMID- 15981737
TI  - The end of print: digitization and its consequence--revolutionary changes in
      scholarly and social communication and in scientific research.
AB  - The transformation from print to digital media for scientific communication,
      driven in part by the growth of the Internet and the tremendous explosion in the
      amount of information now available to everybody, is creating fundamental changes
      in institutions such as publishers, libraries, and universities that primarily
      exist for the creation, management, and distribution of information and
      knowledge. Scientific, technological, and medical journals are the first
      publications to be completely transformed from print to digital format but
      monographs are beginning to appear in digital format as well and soon all
      communication and publishing of scientific information will be entirely
      electronic. In fact, this change is affecting all components of the scientific
      enterprise, from personal correspondence and laboratory methods to peer reviewing
      and the quality assessment of scientific research. Along with these radical and
      rapid changes in information presentation and distribution are coincident changes
      in the expectations of both the public and other scientists, with both groups
      demanding ever more rapid, open, and global access to scientific information than
      has been available in the past. The consequence of this revolution in the
      mechanics of communications technology is threatening the very existence of a
      number of highly regarded institutions such as intellectual property, commercial
      publishers, scientific societies, and academic libraries and might soon begin to
      threaten even the traditional university.

PMID- 15981738
TI  - Rat tissue and blood partition coefficients for n-alkanes (C8 to C12).
AB  - Rat tissue:air and blood:air partition coefficients (PCs) for octane, nonane,
      decane, undecane, and dodecane (n-C8 to n-C12 n-alkanes) were determined by vial
      equilibration. The blood:air PC values for n-C8 to n-C12 were 3.1, 5.8, 8.1,
      20.4, and 24.6, respectively. The lipid solubility of n-alkanes increases with
      carbon length, suggesting that lipid solubility is an important determinant in
      describing n-alkane blood:air PC values. The muscle:blood, liver: blood,
      brain:blood, and fat:blood PC values were octane (1.0, 1.9, 1.4, and 247), nonane
      (0.8, 1.9, 3.8, and 274), decane (0.9, 2.0, 4.8, and 328), undecane (0.7, 1.5,
      1.7, and 529), and dodecane (1.2, 1.9, 19.8, and 671), respectively. The
      tissue:blood PC values were greatest in fat and the least in muscle. The
      brain:air PC value for undecane was inconsistent with other n-alkane values.
      Using the measured partition coefficient values of these n-alkanes, linear
      regression was used to predict tissue (except brain) and blood:air partition
      coefficient values for larger n-alkanes, tridecane, tetradecane, pentadecane,
      hexadecane, and heptadecane (n-C13 to n-C17). Good agreement between measured and
      predicted tissue:air and blood:air partition coefficient values for n-C8 to n-Cl2
      offer confidence in the partition coefficient predictions for longer chain n
      alkanes.

PMID- 15981739
TI  - Influence of gender on cocaine hepatotoxicity in CF-1 mice.
AB  - Gender is known to play a role in the bioavailability, metabolism, and lethality
      of many toxic substances. This study was conducted to investigate the influence
      of gender on cocaine hepatotoxicity (CH) and lipopolysaccharide (LPS)
      potentiation of CH. Male and female CF-1 mice were orally administered 20 mg/kg
      body weight cocaine hydrochloride once daily for 7 days. Four hours after the
      last cocaine administration, the mice were administered 12 x 10(6) EU LPS (or
      equal volume of sterile saline) intraperitoneally. Plasma alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were evaluated as
      indices of liver injury. Blood and liver glutathione (GSH), glutathione reductase
      (GRx), and catalase (CAT) activities were also determined to investigate the
      extent of oxidative stress induced by the treatments. Serum ALT and AST
      concentrations were elevated in all males receiving cocaine alone or cocaine +
      LPS. Furthermore, blood GSH and CAT were decreased and GRx activity was elevated
      in these same animals. Histological analysis revealed a high degree of hepatic
      focal necrosis in the male cocaine group, and severe hemorrhagic necrosis in the
      male cocaine + LPS group. Unlike males, females showed no damage resulting from
      cocaine or cocaine + LPS exposure, whereas testosterone-supplemented
      ovariectomized females displayed histological and biochemical profiles
      statistically similar to males. The results demonstrate that the extent of CH or
      LPS-potentiated CH is influenced by gender and sex hormones, particularly
      testosterone.

PMID- 15981740
TI  - Effects of 1,3,5-Trinitrobenzene on cytotoxicity and metabolic activity of type I
      astrocytes of rats.
AB  - 1,3,5-Trinitrobenzene (TNB) is a munitions chemical that causes gliovascular
      lesions in the brain stem of rats similar to those produced by thiamine
      deficiency and nitroaromatic compounds, including m-dinitrobenzene. To identify
      neuropathic indices of toxicity, the effects of varying concentrations (0 to 2
      mM) of TNB on cytotoxicity and cellular metabolic activity were examined using
      cultured astrocytes from Fischer-344 rats. The cytotoxicity was assessed by
      lactate dehydrogenase (LDH) leakage into the culture medium. Astrocyte metabolic
      activity was assessed by measuring the conversion of a tetrazolium salt to a
      formazan product. Additionally, the effects of oxidative stress on cellular
      metabolic activity were determined by varying oxygen tension via alteration of
      culture media depth. In vitro, the toxic concentration 50% (TC50) of TNB, which
      induced cell death, was 16 microM following a 24-h exposure. The concentration of
      TNB that reduced cellular metabolic activity by 50% was 29 microM following a 24
      h exposure. Varying the depth of the culture media did not influence the cellular
      metabolic activity in control or TNB-treated astrocytes. These results support
      the hypothesis that TNB induced neurotoxicity could partially be mediated via
      injury to astrocytes, a major component of the blood-brain barrier.

PMID- 15981741
TI  - 90-day repeated inhalation exposure of surfactant Protein-C/tumor necrosis factor
      alpha, (SP-C/TNF-alpha) transgenic mice to air pollutants.
AB  - Tumor necrosis factor (TNF)-alpha, a cytokine present in inflammed lungs, is
      known to mediate some of the adverse effects of ozone and inhaled particles. The
      authors evaluated transgenic mice with constitutive pulmonary expression of TNF
      alpha under transcriptional regulation of the surfactant protein-C promoter as an
      animal model of biological susceptibility to air pollutants. To simulate a
      repeated, episodic exposure to air pollutants, wild-type and TNF mice inhaled air
      or a mixture of ozone (0.4 ppm) and urban particles (EHC-93, 4.8 mg/m3) for 4 h,
      once per week, for 12 consecutive weeks and were sacrificed 20 h after last
      exposure. TNF mice exhibited chronic lung inflammation with septal thickening,
      alveolar enlargement, and elevated protein and cellularity in bronchoalveolar
      lavage fluid (genotype main effect, p < .001). Repeated exposure to pollutants
      did not result in measurable inflammatory changes in wild-type mice and did not
      exacerbate the inflammation in TNF mice. The pollutants decreased recovery of
      alveolar macrophages in tavage fluid of both wild-type and TNF mice (exposure
      main effect, p < .001). Exacerbation of the rate of protein nitration reactions
      specifically in the lungs of TNF mice was revealed by the high ratio of 3
      nitrotyrosine to L-DOPA after exposure to the air pollutants (Genotype x Exposure
      factor interaction, p = .014). Serum creatine kinase-MM isoform increased in TNF
      mice exposed to pollutants (Genotype X Exposure factor interaction, p = .043).
      The marked pollutant-related nitration in the lungs of the TNF mice reveals basic
      differences in free radical generation and scavenging in the inflamed lungs in
      response to pollutants. Furthermore, elevation of circulating creatine kinase-MM
      isoform specifically in TNF mice exposed to pollutants suggests systemic adverse
      impacts from lung inflammatory mediators, possibly on muscles and the
      cardiovascular system.

PMID- 15981742
TI  - Physiological and pathological aspects of GSH metabolism.
AB  - The antioxidant glutathione is found in low levels in diseases in which
      increasing evidence implicate oxidative stress in the development of the disease,
      for example retinopathy of prematurity, necrotizing enterocolitis,
      bronchopulmonary dysplasia, patent ductus arteriosus and asthma. Glutathione is
      metabolized in the gamma-glutamyl cycle, which involves six different enzymes.
      The synthesis of glutathione is a two-step process in which the first step is
      catalysed by gamma-glutamylcysteine synthetase and the second step by glutathione
      synthetase. Glutathione synthetase deficiency is an autosomal recessive disease
      and the most common inborn error of the gamma-glutamyl cycle. Approximately 25%
      of patients with hereditary glutathione synthetase deficiency die during
      childhood. Patients present with a clinical picture ranging from compensated
      haemolytic anaemia to a complex disorder with additional symptoms like 5
      oxoprolinuria, metabolic acidosis and central nervous system impairment. Even
      though the correlation between phenotype and genotype in these patients is
      complex, an indication of the phenotype can be based on the type of mutation
      involved. Also, there is a correlation between the glutathione synthetase
      activity and the level of glutathione in cultured fibroblasts. Inborn errors have
      also been described in three additional steps of the y-glutamyl cycle, namely
      gamma-glutamyl-transpeptidase, 5-oxoprolinase and gamma-glutamylcysteine
      synthetase. CONCLUSION: The range of disorders in patients with inborn errors in
      the metabolism of glutathione illustrates the intricate metabolism of glutathione
      and its involvement in numerous essential processes in the cell. By studying
      these patients, further insight into the functions and metabolism of glutathione
      can be achieved.

PMID- 15981743
TI  - Blood pressure in the neonate.
AB  - The paper by Dannevig et al. in this issue of Acta Paediatrica carefully compares
      the agreement between blood pressure measurements made by three non-invasive
      blood pressure monitors with those made from an indwelling intra-arterial
      catheter. Non-invasive blood pressure monitoring is not particularly accurate for
      making measurements in neonates and generally overestimates the blood pressure as
      observed by others. Clinicians thus should be wary about using non-invasive blood
      pressure techniques as substitutes for monitoring by means of an intra-arterial
      catheter and transducer.

PMID- 15981744
TI  - Views on neonatal care of newborns weighing less than 500 grams.
AB  - The limit of viability is intensely debated. Newborns below 500 g birthweight are
      often small for gestational age with an increased risk of short- and long-term
      mortality and morbidity. The level of given neonatal care must be individualized.
      A long-term follow-up for newborns with extremely low birthweight is urgently
      needed.

PMID- 15981745
TI  - Low soluble Fas (sFas) and sFas ligand (sFasL) content in breast milk after
      preterm as opposed to term delivery.
AB  - AIM: Various mechanisms of innate immunity and gastrointestinal integrity are
      potentially affected by soluble Fas (sFas) and sFas ligand (sFasL). Assuming that
      sFas and sFasL in milk reflect cellular events during lactogenesis, we aimed to
      assess the impact of premature parturition and duration of lactation on the
      concentrations of sFas and sFasL in human milk. PATIENTS AND METHODS: The content
      of the soluble form of the cell surface receptor Fas (sFas) and its natural
      ligand (sFasL) was measured in human breast milk of 44 healthy mothers after
      preterm (<35 wk, n=21) and term (>37 wk, n=23) delivery. Milk was furthermore
      classified as immature breast milk (days 4-7 of lactation) or mature breast milk
      (days 35-45 of lactation). Breast milk (2-3 ml) was sampled 5 min after the start
      of breastfeeding by manual expression or milk pump, and stored at -20 degrees C
      until analysis by an ELISA. RESULTS: sFas and sFasL concentrations were lower in
      immature milk after preterm compared to term delivery (sFas: 1.71; 1.38-2.47
      ng/ml vs 3.03; 2.02-4.30 ng/ml, p < 0.001; sFasL: 0.13; 0.07-0.21 ng/ml vs 0.29;
      0.15-0.60 ng/ml, p < 0.001 [median +/- interquartile range]). Mature milk
      samples, taken 1 mo later from both gestational groups, did not differ in
      sFas/sFasL content. Soluble Fas was positively correlated with sFasL in the same
      sample of immature (p < 0.001) and mature human milk (p < 0.05). A positive
      correlation was found between sFas and sFasL in immature and mature milk samples
      of the same mother (p < 0.01). The body mass index of the mothers and duration of
      pregnancy were positively correlated with the sFas and sFasL content in immature
      milk (p < 0.05 and p < 0.01, respectively) but not in mature milk. CONCLUSION:
      Preterm newborn infants fed with breast milk have a lower intake of sFas and
      sFasL compared to term neonates. Our results demonstrate that preterm delivery
      affects breast milk composition.

PMID- 15981746
TI  - Effects of early intake of fruit or vegetables in relation to later asthma and
      allergic sensitization in school-age children.
AB  - AIM: To assess the associations between nutrition supplements in infancy and
      later asthma and allergy in school-age children, and to explore the impact of
      environmental factors in early life. METHODS: Five hundred and two children
      underwent clinical examination, skin prick test and a second parentally completed
      questionnaire within 2 y of a cross-sectional questionnairebased study, including
      4585 primary school children (6-16 y old) in 1994 from urban Oslo (37%), the
      mountainous area of Hallingdal (42%), and the industrial, coastal area of Odda
      (21%). The children were selected from the 1994 survey on the basis of reported
      diagnosed asthma (n=166), wheeze in the last 12 mo (n=155) and no asthma/no
      wheeze (n=181). Questions were related to nutrition and environmental exposure in
      early life. Possible associations between allergic sensitization or asthma at
      school age and exposures were estimated by logistic regression analysis,
      adjusting for potential confounders. RESULTS: Daily intake of fresh fruit or
      vegetables, but not extra vitamins or cod liver oil supplements, in infancy
      decreased the risk of asthma (adjusted odds ratio (aOR) 0.57 (95% confidence
      interval (CI): 0.37-0.88). Early supplements of cod liver oil and extra vitamins
      were associated with increased allergic sensitization (aOR 1.78 (95% CI: 1.03
      3.07) and 1.71 (95% CI: 1.01-2.88), respectively). A significantly higher
      prevalence of allergic sensitization was found in children living in Hallingdal
      compared to Odda, while the latter children, on the other hand, had the highest
      prevalence of house dust mite allergy (p = 0.001 vs Hallingdal and p = 0.04 vs
      Oslo). CONCLUSION: The present study suggests that the early introduction of
      daily fresh fruit or vegetables may decrease the risk of asthma after 1 y of
      life, whereas allergic sensitization at school age seemed to increase with extra
      vitamin and cod liver oil supplements during infancy. Living area influenced
      allergic sensitization, with differences between coastal and inland areas.

PMID- 15981747
TI  - Is procalcitonin useful in early diagnosis of serious bacterial infections in
      children?
AB  - AIM: To compare diagnostic accuracy of procalcitonin for early diagnosis of
      serious bacterial infection (SBI) in children presenting with fever and no focus
      of infection. METHODS: Prospective, observational study involving 72 children (1
      36 mo) presenting to the paediatric units of two university hospitals. All
      children had blood cultures, urine cultures, white blood cell counts (WBC), chest
      X-ray, C-reactive protein (CRP) and procalcitonin (PCT) done at presentation.
      RESULTS: Eight (11.1%) children had SBI (1 pneumonia, 2 meningitis, 4
      septicaemia/occult bacteraemia, 2 pyelonephritis), 19 (26.4%) had possible
      bacterial infection (received antibiotic treatment, but no organism grown) and 45
      (62.5%) had viral or possible viral infection (virus isolated and/or uneventful
      recovery without antibiotics). PCT (>2 ng/l), CRP (>50 mg/l) and McCarthy's score
      (<9) had sensitivities and specificities of 50%/85.9%, 75%/68.7% and 87.5%/67.2%,
      respectively. Negative and positive likelihood ratios for CRP (>50 mg/l), PCT (>2
      ng/l), white blood cells (>15 x 10(5)/l) and McCarthy's score (<9) were 0.36/2.4,
      0.58/3.5, 0.94/1.1 and 0.19/2.7, respectively. A combination of PCT, CRP and WBC
      generated a positive likelihood ratio of 10.6, changing the post-test probability
      to 54%. CONCLUSION: For early diagnosis of SBI in children presenting with fever
      and no focus of infection, the diagnostic utility of procalcitonin is similar to
      the traditional markers infection and clinical scoring. While a low procalcitonin
      level cannot be used to exclude SBI in this population, a combination of PCT, CRP
      and WBC may be more useful in predicting SBI.

PMID- 15981748
TI  - Respiratory syncytial virus infection in children hospitalized for wheezing:
      virus-specific studies from infancy to preschool years.
AB  - AIM: To evaluate whether the presence of immunoglobulin G (IgG) antibodies
      against respiratory syncytial virus (RSV) in early childhood is associated with
      later asthma, and to evaluate a new diagnostic test for RSV, reverse
      transcription polymerase chain reaction (RT-PCR), comparing it to the antigen and
      antibody assays initially used in RSV diagnostics in the present cohort. METHODS:
      At the start of the study in 1992-1993, RSV was studied by antigen detection
      (using time-resolved fluoroimmunoassay) and complement-fixing antibody assay.
      Advances in methodology allowed us to supplement RSV studies by RT-PCR in frozen
      nasopharyngeal aspirates obtained on admission, and by specific IgG antibodies
      (using enzyme immunoassay) in frozen serum samples obtained during the follow-up.
      RESULTS: On admission, 29 of the 100 children hospitalized for wheezing at <2 y
      of age were RSV positive. When compared with conventional methods, the
      sensitivity of RT-PCR was 83% (100% w.r.t. antigen detection) and its specificity
      was 92% in diagnosing RSV infection. RSV-specific IgG antibody concentrations
      rose with age, but were not predictive of asthma at any age. In the present
      cohort, wheezing without RSV was particularly associated with increased risk for
      later childhood asthma. CONCLUSION: Hospitalization for wheezing in infancy is
      associated with increased risk for later childhood asthma, particularly in
      children without RSV infection on admission, although children with RSV have also
      slightly increased risk for later asthma. However, mere serological evidence of
      RSV infection is not associated with the development of asthma. In addition to
      RSV, more attention should be paid to less virulent agents in order to find those
      wheezing infants who are at particular risk of later childhood asthma.

PMID- 15981749
TI  - Mastitis in early infancy.
AB  - AIM: To evaluate the clinical features and microbiological findings in young
      infants with mastitis. METHODS: Retrospective review of medical records of 18
      infants with breast inflammation during the first 3 mo of life seen in the
      paediatric emergency department between 1992 and 2002. RESULTS: All were full
      term infants with female-male ratio of 3.5:1. The age ranged from 12 to 45 d,
      with a peak in the 4th and 5th weeks of life. Only five patients had systemic
      manifestations, and five were pretreated with oral antibiotics (amoxicillin
      clavulanic acid). The latter as well as seven additional cases required incision
      and drainage due to abscess formation. Bacterial cultures grew Staphylococcus
      aureus in 10 cases including all pretreated infants. In four of these cases, Gram
      stain showed the pathogen. After antimicrobial treatment, no recurrence was
      observed in any of the patients. CONCLUSIONS: These findings suggest that
      mastitis in early infancy should be treated with parenteral antibiotics guided by
      Gram stain when available and informative. Otherwise, beta-lactamase-resistant
      antibiotics are a reasonable empirical initial treatment pending culture results.
      Optimizing the management of infants with mastitis is important especially since
      abscess formation requiring incision may be detrimental for later breast
      development.

PMID- 15981750
TI  - Homeostatic role of IL-7 in HIV-1 infected children on HAART: association with
      immunological and virological parameters.
AB  - AIM: To investigate the role of IL-7 in HIV-infected children on highly active
      antiretroviral therapy (HAART) and its association with laboratory parameters
      related to disease progression. PATIENTS AND METHODS: A cross-sectional study in
      31 vertically HIV-infected children (median age 8.4 y) treated with HAART, and a
      longitudinal study in four of those same children was carried out. In both
      studies, viral load, CD4+ T-cell counts, thymic production of T cells by TCR
      rearrangement excision circles (TRECs), IL-7 plasma levels and viral phenotype
      were determined. RESULTS: IL-7 levels were higher in HIV-infected children than
      in age-matched, uninfected controls. In addition, HIV children with CD4+ T cells
      between 200 and 500 T cells/mm3 had higher IL-7 levels and lower TREC values than
      HIV-infected children with CD4+ T cells >500 T cells/mm3. IL-7 levels were higher
      in children with syncytium-inducing (SI) phenotype than in those with non
      syncytium-inducing (NSI) variants. During the follow-up of four HIV children, the
      decrease in viral load after HAART was always associated with a recovery of CD4+
      T cells and TRECs, which was followed by a decrease in IL-7 returning to the
      levels present prior to the drop in CD4+ T cells. The four HIV-infected children
      had SI/X4 isolates in PBMC before HAART, and the viral phenotype switched to
      NSI/R5 after HAART. CONCLUSION: Our data suggest that IL-7 plays a key role in
      the maintenance of T-cell homeostasis in HIV-infected children on HAART, both
      through peripheral expansion and through a thymus-dependent mechanism.

PMID- 15981751
TI  - Childhood idiopathic thrombocytopenic purpura in the Nordic countries:
      epidemiology and predictors of chronic disease.
AB  - AIM: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in
      the Nordic countries, to define clinical subgroups and to investigate factors
      predicting chronic disease. METHODS: A prospective registration was done from
      1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at
      least one platelet count <30 x 10(9)/l. RESULTS: 506 children were registered and
      423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were
      aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had
      equal representation of the two sexes. There were seasonal variations determined
      by variations in postinfectious cases with sudden onset. The platelet count was
      <10 x 10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%.
      The insidious form (symptoms for more than 2 wk) was more frequent in older
      children and girls, showed little seasonal variation, had milder manifestations
      and ran a chronic course in more than half the cases. Intracranial haemorrhages
      did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%.
      The strongest predictor of chronic disease was insidious onset of symptoms (OR
      5.97). CONCLUSION: In the Nordic countries, ITP mainly affects children aged 0-7
      y, with a winter bulk of postinfectious cases superimposed on a steady occurrence
      of non-infectious cases. Clinically, it may be useful to distinguish between
      children with sudden versus insidious onset of symptoms rather than between
      different age groups.

PMID- 15981752
TI  - Pathophysiology of neonatal brain lesions: lessons from animal models of
      excitotoxicity.
AB  - AIM: The pathophysiology of perinatal brain lesions is probably complex and
      multifactorial. The development and characterization of distinct yet
      complementary animal models should help to unravel the cellular and molecular
      mechanisms underlying perinatal brain lesions. This paper reviews experimental
      data obtained in animal models of neonatal excitotoxic brain lesions that closely
      mimic some of the lesions found in human cerebral palsy. CONCLUSION: Available
      data point to a key role for brain macrophages and oligodendrocytes in neonatal
      rodent excitotoxic brain lesions and underline the impact of cytokines on these
      lesions.

PMID- 15981753
TI  - Blood pressure in the neonate: three non-invasive oscillometric pressure monitors
      compared with invasively measured blood pressure.
AB  - AIM: To compare blood pressure in neonates obtained from three different
      oscillometer blood pressure monitors (Dinamap, Criticare, Hewlett-Packard) with
      arterial blood pressure (Hewlett-Packard' invasive unit). STUDY DESIGN: A total
      of 32 randomized, non-invasive blood pressure series, each consisting of three
      measurements from each monitor, were obtained from 20 neonates (birthweight 531
      4660 g). Each measurement was compared with the invasive pressure. RESULTS: Two
      factors appear to have a systematic effect on the difference between
      oscillometric and invasive pressure (the measurement deviance): the size of the
      infant, e.g., the arm circumference, and the monitor system. For small infants,
      the non-invasively measured value tends to be too high. The deviance is partly
      reversed for larger infants (dependency on size significant for mean and
      diastolic pressure, p < 0.001). The difference between monitor systems is clearly
      significant (p < 0.001). Hewlett-Packard gives the lowest pressure values for all
      pressures. Thus, Criticare and Dinamap tended to show values too high in the
      smallest infants, while Hewlett-Packard tended to give values too low in larger
      infants. Birthweight, present weight and arm circumference affected measurement
      deviance approximately equally strongly, while factors such as the infant's sex,
      need of breath support and umbilical or radial arterial line were non
      significant. CONCLUSIONS: Blood pressure should preferably be measured invasively
      in severely ill neonates and preterm infants, being aware of pitfalls with
      measurements using different oscillometer monitors and the size/arm circumference
      of the infant.

PMID- 15981754
TI  - A randomized trial comparing oxygen delivery on intermittent positive pressure
      with nasal cannulae versus facial mask in neonatal primary resuscitation.
AB  - AIM: To compare, in a prospective clinical trial, oxygen delivery on intermittent
      positive pressure with nasal cannulae versus facial mask in primary resuscitation
      of the newborn with moderate asphyxia. METHODS: 617 neonates with moderate
      asphyxia at birth were randomized: 303 were resuscitated by oxygen on
      intermittent positive pressure with nasal cannuale and 314 neonates by mask.
      Resuscitation followed the Neonatal Resuscitation Program guidelines of the
      American Academy of Pediatrics, 3rd edition. RESULTS: Resuscitation through the
      nasal route less frequently requires chest compressions and intubations (26
      neonates needed chest compression and 20 needed intubation out of 314
      resuscitated by mask; five neonates needed chest compression and two needed
      intubation out of 303 resuscitated by nasal cannulae). Apgar scores, admission
      rates to neonatal intensive care units, air-leak syndromes, birthweight,
      gestational age, use of prenatal steroids and deaths did not differ between
      groups. CONCLUSION: Oxygen delivery on intermittent positive pressure with nasal
      cannulae in primary resuscitation of the newborn with moderate asphyxia is a less
      aggressive and potentially advantageous alternative to the traditional oral
      route.

PMID- 15981755
TI  - VWF-cleaving protease (ADAMTS13) in premature infants.
AB  - BACKGROUND: Patients with thrombotic thrombocytopenic purpura (TTP) are deficient
      in von Willebrand factor (VWF)-cleaving protease, called ADAMTS13, and are prone
      to develop abnormal intravascular platelet aggregation leading to focal cerebral
      ischaemia. We speculated that low levels of ADAMTS13 are present in premature
      infants. This might result in platelet aggregation with subsequent ischaemia,
      vessel rupture and haemorrhage, and thus contribute to intraventricular
      haemorrhage and periventricular leucomalacia (IVH and PVL). PATIENTS AND METHODS:
      Nine preterm infants with gestational ages 23.7 to 30.9 (median 25.7) wk, and 10
      healthy term control infants with gestational ages 36.9 to 39 (median 37.9) wk
      were included. Blood was sampled from the umbilical cord at delivery, and levels
      of ADAMTS13, VWF antigen and VWF collagen binding activity were analysed.
      RESULTS: The mean ADAMTS13 level in preterm infants was lower than in the term
      infants, but the difference between the groups was not statistically significant.
      However, in the preterm group there was a positive correlation between ADAMTS13
      and both gestational age (r = 0.70, p = 0.035) and birthweight (r = 0.83, p =
      0.005). Three preterm infants had ADAMTS13 of 18-20%. One of these developed a
      germinal matrix haemorrhage and PVL, and this infant had the lowest measured
      ADAMTS13 of all. The levels of VWF antigenand VWF collagen bindingactivity were
      higher in the preterm infants. CONCLUSION: This pilot study showed that preterm
      infants have low levels of ADAMTS13. Enzyme substitution may be a therapeutic
      option if an association with IVH or PVL can be confirmed in larger patient
      groups.

PMID- 15981756
TI  - Short-term outcome in infants with a birthweight less than 501 grams.
AB  - AIM: To report survival and morbidity until discharge in preterm infants <501 g
      with life support started immediately after birth. METHODS/STUDY DESIGN: Cohort
      study of all preterm infants with birthweights < 501 g born in three tertiary
      perinatal centres between 1 January 1998 and 31 December 2001 (gestational age
      (GA) 25.2 [21.0-30.7] wk; birthweight 435 [290-500] g; median [range]). RESULTS:
      A total of 107 infants with birthweights <501 g were born. Twenty-nine were
      stillborn. A prenatal decision to initiate life support immediately after birth
      was reached in 9/37 (24%) infants <24.0 wk GA and in 39/42 (93%) infants > or
      =24.0 wk GA. Survival was 3/37 (8%) and 26/41 (63%) in infants <24 wk GA and > or
      =24.0 wk GA, respectively. Twenty-nine of the 48 infants with immediate life
      support (60%) survived (95% CI: 46-75%). Forty-two of these 48 (88%) infants were
      small for gestational age. No infant without immediate life support survived
      (0/30). Twenty-three (79%) survivors developed chronic lung disease (CLD) and
      eight (28%) received photocoagulation for retinopathy of prematurity (ROP).
      CONCLUSION: In this population of extremely low birthweight infants, survival was
      higher than in previous studies when life support was provided immediately after
      birth. Short-term morbidity was similar to other studies. The presented data on
      survival support our concept to offer immediate life support after birth in
      preterm infants with birthweights <501 g. The long-term outcome of these infants
      needs to be assessed urgently.

PMID- 15981757
TI  - Exposure to tobacco smoke and infant crying.
AB  - AIM: To examine the association of excessive infant crying with maternal smoking
      during and after pregnancy, paternal smoking, and smoking by other people in the
      living environment of the infant. METHODS: We collected data on infant crying and
      smoking in a Dutch national sample of 5845 infants aged 0-3 mo (response 62.8%).
      We defined excessive crying as crying over 3 h a day on more than 3 d of the
      preceding week. RESULTS: The prevalence rate of excessive crying was 4.0% (95% CI
      3.5 to 4.5%). Excessive crying occurred more frequently among infants of fathers
      smoking 15 + cigarettes/d (odds ratio (OR) 1.99, 95% CI 1.38 to 2.86) and of
      mothers smoking 10 + cigarettes/d during pregnancy (OR 1.86, 95% CI 1.02 to
      3.42). Infants whose parents were heavy current smokers or whose mothers had been
      so during pregnancy had a 69% higher prevalence of excessive crying than infants
      of non-smoking parents (rates: 6.3% and 3.7%, respectively; odds ratio 1.80; 95%
      CI 1.26 to 2.57). CONCLUSION: Parents stopping smoking may prevent excessive
      infant crying.

PMID- 15981758
TI  - Home-based therapy with ready-to-use therapeutic food is of benefit to
      malnourished, HIV-infected Malawian children.
AB  - AIM: To determine if home-based nutritional therapy will benefit a significant
      fraction of malnourished, HIV-infected Malawian children, and to determine if
      ready-to-use therapeutic food (RUTF) is more effective in home-based nutritional
      therapy than traditional foods. METHODS: 93 HIV-positive children >1 y old
      discharged from the nutrition unit in Blantyre, Malawi were systematically
      allocated to one of three dietary regimens: RUTF, RUTF supplement or blended
      maize/soy flour. RUTF and maize/soy flour provided 730 kJ x kg(-1) x d(-1), while
      the RUTF supplement provided a fixed amount of energy, 2100 kJ/d. These children
      did not receive antiretroviral chemotherapy. Children were followed fortnightly.
      Children completed the study when they reached 100% weight-for-height, relapsed
      or died. Outcomes were compared using regression modeling to account for
      differences in the severity of malnutrition between the dietary groups. RESULTS:
      52/93 (56%) of all children reached 100% weight-for-height. Regression modeling
      found that the children receiving RUTF gained weight more rapidly and were more
      likely to reach 100% weight-for-height than the other two dietary groups (p <
      0.05). CONCLUSION: More than half of malnourished, HIV-infected children not
      receiving antiretroviral chemotherapy benefit from home-based nutritional
      rehabilitation. Home-based therapy RUTF is associated with more rapid weight gain
      and a higher likelihood of reaching 100% weight-for-height.

PMID- 15981759
TI  - A randomized controlled trial of an asthma clinical pathway for children in
      general practice.
AB  - AIMS: To evaluate the effect of the implementation of an asthma clinical pathway
      on asthma in children in general practice. METHODS: A randomized, controlled
      trial involving 270 general practitioners. One group of general practitioners
      implemented the asthma clinical pathway for children (intervention group) and the
      control group continued with their usual asthma medical care management. The main
      outcome measures were admissions to hospital for asthma and attendance at the
      Children's Emergency Department. Compliance with the guidelines was assessed by
      examining asthma drug prescriptions. RESULTS: Admissions to hospital for asthma
      dropped 40% in the intervention group, by 33% in the control group and by 22% in
      general practitioners not participating in the trial. The differences between the
      intervention and control and between the intervention and non-participating
      general practitioners were not statistically significant. The decrease in
      attendance at the Children's Emergency Department decreased by 25%, 30% and 19%,
      respectively, but this was not statistically significant. There was a significant
      decrease in prescriptions for oral relievers, dry powder relievers in the under
      6s, mast cell stabilizers and methylxanthines in both control and intervention
      groups. However, only for oral relievers was there a significant difference
      between the intervention group and control, with the decrease larger in the
      intervention group (p < 0.001). CONCLUSIONS: Admissions to hospital for asthma
      decreased, as did attendance at the Children's Emergency Department.
      Prescriptions for asthma medication changed in the direction anticipated with
      compliance with the asthma clinical pathway. However, we found no evidence within
      the study that implementation of the asthma clinical pathway by general
      practitioners resulted in lower morbidity than those general practitioners who
      did not implement the pathway. Possible explanations are that these general
      practitioners were already providing care according to the recommendations of the
      pathway, or that there was contamination of the control group by the
      intervention, or that the guidelines, although based on currently accepted
      recommendations, are ineffective.

PMID- 15981760
TI  - Recurrent abdominal pain: a five-year follow-up study.
AB  - To explore the long-term prognosis for children referred for recurrent abdominal
      pain (RAP), 44 children investigated for RAP 5 y ago were compared to a group of
      controls (n=88). The former RAP patients reported RAP, headache and school
      absence more frequently than controls. A high proportion of children referred
      with RAP have persistent symptoms, with more headache and school absence than
      controls. The diagnostic subgroup did not predict persistence of abdominal pain.

PMID- 15981761
TI  - What is the yield from asking, at the end of the consultation, if there are any
      further questions? An observational study.
AB  - AIM: I set out to determine how often families, when invited, have further
      questions at the end of a general paediatric consultation and to determine the
      nature of such questions. RESULTS: Over a 2 1/2 -y period, there were 64 further
      questions arising from a total of 477 consultations (13%). CONCLUSIONS: Inviting
      questions is worthwhile; two-thirds of the responses provided evidence that there
      had been suboptimal communication during the consultation.

PMID- 15981762
TI  - Thrombolytic therapy with tissue plasminogen activator for superior vena cava
      thrombosis in an infant with sepsis.
AB  - Superior vena cava syndrome is rare in infants, and rarely responds to
      conservative treatment. We report a 22-mo-old girl with superior vena cava
      syndrome due to the use of a central venous line and/or sepsis. Doppler study and
      computed tomography angiography of the neck showed thrombosis within the superior
      vena cava and jugular veins. She was admitted to a monitored setting and received
      recombinant tissue plasminogen activator for 2 d. The clinical features of
      superior vena cava syndrome disappeared completely 3 d after treatment. No
      complications were observed and radiological investigations showed blood flow
      through the thrombus after treatment. Systemic recombinant tissue plasminogen
      activator may be useful in the treatment of superior vena cava syndrome in
      children.

PMID- 15981763
TI  - Deep venous thrombosis in a child associated with an abnormal inferior vena cava.
AB  - Congenital anomalies of the inferior vena cava (IVC), such as absence or atresia,
      although well documented, are uncommon and result from aberrant development
      during embryogenesis. Absence or atresia of the IVC is usually discovered
      accidentally. Patients are typically asymptomatic of the condition itself. Many
      concurrent cardiovascular-associated abnormalities have been described. We report
      a 10-y-old boy admitted to the emergency room with painful swelling of his right
      lower limb without previous trauma or surgery. After 3 d, swelling also involved
      the left lower limb. A Doppler ultrasound of the lower limbs revealed bilateral
      thrombosis of the vena iliaca communis, vena iliaca externa, femoral vein
      communis and superficial extending to the IVC. Magnetic resonance imaging (MRI)
      of the abdomen was performed. On MRI, we demonstrated a hypoplastic IVC. The
      results of blood coagulation studies, including levels of antiphospholipid
      antibodies, proteins C and S, and antithrombin III, were normal. The patient was
      treated with intravenous heparin for 8 d and discharged with oral warfarin
      therapy, which has been recommended for life. Therapy against deep venous
      thrombosis must be focused on its prevention in the future. An abnormal inferior
      vena cava should be considered in young patients with deep venous thrombosis
      without apparent cause.

PMID- 15981764
TI  - Extensive cervical spinal cord lesion with late foetal presentation.
AB  - Neonatal cervical spinal cord injury occurring in the perinatal period is rare
      but has been described after both traumatic and atraumatic birth. Recently, a
      case of atraumatic, late third trimester, pre-labour presentation has been
      described. We report a second such case, but with important diagnostic
      differences and outcome. This case showed loss of foetal movements late in the
      third trimester. This was secondary to an extensive cervical lesion with no
      history of trauma. This emphasizes the need to consider cervical cord lesions
      when foetal or postnatal movements are reduced, even in the absence of trauma.

PMID- 15981765
TI  - Non-progressive congenital ataxia with cerebellar hypoplasia in three families.
AB  - AIM: Non-progressive ataxias with cerebellar hypoplasia are a rarely seen
      heterogeneous group of hereditary cerebellar ataxias. METHOD: Three sib pairs
      from three different families with this entity have been reviewed, and
      differential diagnosis has been discussed. RESULTS: In two of the families, the
      parents were consanguineous. Walking was delayed in all the children. Truncal and
      extremity ataxia were then noticed. Ataxia was severe in one child, moderate in
      two children, and mild in the remaining three. Neurological examination revealed
      horizontal, horizonto-rotatory and/or vertical nystagmus, variable degrees of
      mental retardation, and pyramidal signs besides truncal and extremity ataxia. In
      all the cases, cerebellar hemisphere and vermis hypoplasia were detected in MRI.
      During the follow-up period, a gradual clinical improvement was achieved in all
      the children. CONCLUSION: Inheritance should be considered as autosomal recessive
      in some of the non-progressive ataxic syndromes. Congenital non-progressive
      ataxias are still being investigated due to the rarity of large pedigrees for
      genetic studies. If further information on the aetiopathogenesis and clinical
      progression of childhood ataxias associated with cerebellar hypoplasia is to be
      acquired, a combined evaluation of metabolic screening, long-term follow-up and
      radiological analyses is essential.

PMID- 15981766
TI  - ARC syndrome.

PMID- 15981767
TI  - Fungal peritonitis in peritoneal dialysis patients.
AB  - Peritonitis is one of the most frequent complications of peritoneal dialysis (PD)
      and 1% - 15% of episodes are caused by fungal infections. The mortality rate of
      fungal peritonitis (FP) varies from 5% to 53%; failure to resume PD occurs in up
      to 40% of patients. The majority of these FP episodes are caused by Candida
      species. Candida albicans has historically been reported to be a more common
      cause than non-albicans Candida species, but in recent reports a shift has been
      observed and non-albicans Candida may now be more common. Unusual, often
      "nonpathogenic," fungi are being increasingly reported as etiologic agents in FP.
      Clinical features of FP are not different from those of bacterial peritonitis.
      Phenotypic identification of fungi in clinical microbiology laboratories is often
      difficult and delayed. New molecular diagnostic techniques (e.g., polymerase
      chain reaction) are being developed and evaluated, and may improve diagnosis and
      so facilitate early treatment of infected patients. Abdominal pain, abdominal
      pain with fever, and catheter left in situ are risk factors for mortality and
      technique failure in FP. In programs with high baseline rates of FP, nystatin
      prophylaxis may be beneficial. Each program must examine its own history of FP to
      decide whether prophylaxis would be beneficial. Catheter removal is indicated
      immediately after fungi are identified by Gram stain or culture in all patients
      with FP. Prolonged treatment with antifungal agents to determine response and
      attempt clearance is not encouraged. Antifungals should be continued for 10 days
      to 2 weeks after catheter removal. Attempts at reinsertion should be made only
      after waiting for 4 - 6 weeks.

PMID- 15981768
TI  - Resolving peritoneal inflammation: flicking the right "switches".

PMID- 15981769
TI  - Can biocompatible dialysis fluids improve outcomes in peritoneal dialysis
      patients?

PMID- 15981770
TI  - Time-integrated CRP level strongly predicts PD patient outcomes--nice to know,
      but what should we do about it?

PMID- 15981771
TI  - Both sides now: disclosure of prognosis on dialysis.

PMID- 15981772
TI  - CD40 ligand expression correlates with resolution of peritonitis and mononuclear
      cell recruitment.
AB  - BACKGROUND: CD40 belongs to the tumor necrosis factor receptor family and its
      ligation is a central event in major inflammatory and immune reactions. We have
      previously demonstrated that CD40 ligation upregulates the secretion of
      mononuclear chemokines from peritoneal mesothelial cells (PMC), and that blocking
      the CD40 ligand (CD154) reduced the mononuclear infiltrate in a model of
      peritonitis. OBJECTIVE: To characterize the kinetics of CD154 expression on
      peritoneal Leukocytes and examine the correlation of this occurrence with the
      mononuclear transition at the resolution phase of peritonitis. METHODS:
      Leukocytes were collected from the effluent of 11 patients during episodes of
      peritonitis while undergoing peritoneal dialysis (PD). The effluent was then
      analyzed by flow cytometry to characterize CD154 expression. RESULTS: CD154
      expression on peritoneal mononuclear cells gradually increased during the
      resolution phase of peritonitis, peaking first on T cells (CD4+ and CD8* cells at
      20-45 hours) and then on macrophages (CD14' at 20-50 hours). The maximal
      expression of CD154 on macrophages, CD4* cells, and CD8* cells during peak hours
      reached values of 33% * 23%, 4%-3%, and 24%-17%, respectively. The increase in
      CD154 expression was in-negative correlation (r= -0.44, p = 0.032) with total
      Leukocyte numbers and in positive correlation (r = 0.52, p = 0.009) with the
      increase of mononuclear cells. Deterioration of peritonitis was associated with a
      decrease in CD154 levels, while recurrence of peritonitis was related to high
      CD154 Levels. CONCLUSION: Our data, which show a positive correlation between
      CD154 Levels and mononuclear dominance, suggest that CD40-CD154 Ligation plays an
      important role in the transition to mononuclear predominance in the late phase of
      peritonitis.

PMID- 15981773
TI  - Superior patient survival for continuous ambulatory peritoneal dialysis patients
      treated with a peritoneal dialysis fluid with neutral pH and low glucose
      degradation product concentration (Balance).
AB  - BACKGROUND: In recent years, laboratory and clinical research has suggested the
      need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the
      conventional PDFs commonly used today. Bioincompatibility of PDF has been
      attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and
      osmolality. PDFs with neutral pH and low GDPs are now available commercially. In
      vitro and early clinical studies suggest that these solutions are indeed more
      biocompatible but, as of now, there is no evidence that their use improves
      patient outcome. METHODS: Using a dedicated database of over 2000 patients
      treated with PD in Korea, we were able to conduct a retrospective observational
      study comparing outcomes for incident continuous ambulatory PD patients treated
      with a standard, conventional, heat-sterilized PDF to the outcomes for patients
      treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment,
      double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In
      an intention-to-treat analysis, patient and technique survival, peritonitis-free
      survival, and peritonitis rates were compared in 611 patients treated with
      Balance for up to 30 months and 551 patients with a standard PDF (stay . safe;
      Fresenius Medical Care) treated in the same era and with equivalent follow-up.
      RESULTS: The patients were well matched for most relevant characteristics except
      older age distribution for the patients treated with the standard PDF. Patients
      treated with Balance had significantly superior survival compared to those
      treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a
      multivariate Cox regression model including age, diabetes, and gender, the
      survival advantage persisted (relative risk of death for Balance 0.75, 95%
      confidence interval 0.56 - 0.99, p = 0.0465). Modality technique survival was
      similarin Kaplan-Meieranalysis for both PDFs. No differences were detected in
      peritonitis-free survival or in peritonitis rates between the two solutions.
      CONCLUSION: This study, for the first time, suggests that treatment with a novel
      biocompatible PDF with low GDP concentration and neutral pH confers a significant
      survival advantage. The exact mechanisms for such a survival advantage cannot be
      determined from this study. The usual criticisms of observational studies apply
      and the results reported here strongly warrant the undertaking of appropriately
      designed, randomized, controlled clinical trials.

PMID- 15981775
TI  - Nephrologists should voluntarily divulge survival data to potential dialysis
      patients: a questionnaire study.
AB  - BACKGROUND: For many dialysis patients, survival is no different than with
      certain cancers. Yet, it appears that most nephrologists do not give detailed
      information about survival prior to obtaining informed consent for chronic
      dialysis. There are no published data on whether patients wish to be so informed.
      OBJECTIVE: To assess whether patients would want voluntary disclosure by their
      physician of their survival should they need dialysis, and if so, why? METHOD: A
      questionnaire was completed by 100 general nephrology patients during their first
      visit to a nephrologist. RESULTS: The vast majority of patients (97%) would want
      to be given life-expectancy information, and for the physician to do so without
      having to be prompted. Furthermore, the majority of patients would want as much
      information as possible, both good and bad. CONCLUSIONS: Virtually all patients
      want, and therefore should receive from their physician, prognostic information
      about dialysis to facilitate informed decision-making. This is in accordance with
      current practice guidelines.

PMID- 15981774
TI  - The time course of serum C-reactive protein is more predictive of mortality than
      its baseline level in peritoneal dialysis patients.
AB  - BACKGROUND: Several recent studies reported that a high baseline serum C-reactive
      protein (CRP) is a powerful predictor of mortality in dialysis patients. However,
      the acute-phase response is intermittent and not a continuous feature in an
      individual patient. The aim of this prospective study was to determine whether
      serial analysis of serum CRP during follow-up allows better prediction of
      mortality and echocardiographic cardiac disease than a single baseline
      measurement in peritoneal dialysis (PD) patients. METHODS: 97 PD patients were
      monitored for 3 years from the beginning of the treatment. We evaluated the
      effect of demographic features, comorbidity, blood pressure, blood biochemistry,
      including CRP, residual renal function, and indices of dialysis adequacy, on
      mortality and left ventricular hypertrophy (LVH). Cox regression analysis using
      both the baseline and the averaged values of the study parameters was carried out
      to determine factors predicting mortality. Logistic regression analysis was
      performed to determine which factors were independently predictive for LVH and
      the type of time course of serum CRP. RESULTS: Baseline serum CRP was elevated in
      29 patients (29.9%). While serum CRP exhibited a stable course (normal or high)
      in 55 patients (56.7%), it varied considerably over time in 42 patients (43.2%).
      In the Cox models, both the averaged serum CRP and the type of variability of CRP
      were predictors of mortality. On the contrary, baseline CRP did not affect
      adjusted survival. The averaged CRP was also an independent factor affecting LVH,
      but baseline CRP was not. Age, comorbidityindex, instilled dialysate glucose
      concentration, and Kt/V urea were independently associated with the type of time
      course of serum CRP. CONCLUSION: The averaged value of serum CRP is more
      predictive of prognosis compared to the baseline value in PD patients.
      Determining serum CRP on a regular basis may be helpful to detect early signs of
      tissue damage or asymptomatic inflammation.

PMID- 15981776
TI  - Peritonitis-related mortality in patients undergoing chronic peritoneal dialysis.
AB  - Peritonitis is a well-known cause of mortality in peritoneal dialysis (PD)
      patients. We carried out a retrospective study to disclose the clinical spectrum
      and risk profile of peritonitis-related mortality. We analyzed 693 episodes of
      infectious peritonitis suffered by 565 patients (follow-up 1149 patient-years).
      Death was the final outcome in 41 cases (5.9% of episodes), peritonitis being
      directly implicated in 15.2% of the global mortality and 68.5% of the infectious
      mortality observed. In 41.5% of patients with peritonitis-related mortality, the
      immediate cause of death was a cardiovascular event. Highest mortality rates
      corresponded to fungal (27.5%), enteric (19.3%), and Staphylococcus aureus
      (15.2%) peritonitis. Multivariate analysis disclosed thatthe baseline risk of
      peritonitis-related mortality was significantly higher in female [relative risk
      (RR) 2.13, 95% confidence interval (CI) 1.24-4.09, p = 0.02], older (RR
      1.10/year, CI 1.06-1.14, p < 0.0005), and malnourished patients (RR 2.51, CI 1.21
      5.23, p = 0.01) with high serum C-reactive protein (s-CRP) levels (RR 4.04, CI
      1.45-11.32, p = 0.008) and a low glomerular filtration rate (RR 0.75 per
      mL/minute, CI 0.64 -0.87, p < 0.0005). Analysis of risk after a single episode of
      peritonitis and/or subanalysis restricted to peritonitis caused by more
      aggressive micro-organisms disclosed that overall comorbidity [odds ratio (OR)
      1.21, CI 1.05-1.71, p = 0.005], depression (OR 2.35, CI 1.14-4.84, p = 0.02), and
      time on PD at the time of the event (OR 1.02/month, CI 1.00-1.03, p = 0.02) were
      other predictors of mortality. In summary, the etiologic agent is a definite
      marker of peritonitis-related mortality but gender, age, residual renal function,
      inflammation (s-CRP), malnutrition, and depression are other significant
      correlates of this outcome. Most of these risk factors are common to
      cardiovascular and peritonitis-related mortality, which may explain the high
      incidence of cardiovascular event as the immediate cause of death in patients
      with peritonitis-related mortality.

PMID- 15981777
TI  - Successful treatment of encapsulating peritoneal sclerosis with azathioprine and
      prednisolone.

PMID- 15981778
TI  - Analysis of medication use in peritoneal dialysis patients in two units.

PMID- 15981779
TI  - Streptococcus oralis: a rare cause of CAPD-related peritonitis.

PMID- 15981780
TI  - The effect of a Tai Chi exercise program on quality of life in patients on
      peritoneal dialysis: a pilot study.

PMID- 15981781
TI  - Prolene hernia system: an innovative method for hernia repair in patients on
      peritoneal dialysis.

PMID- 15981782
TI  - Peritoneal dialysis catheter erosion into bowel: amyloidosis may be a risk
      factor.

PMID- 15981783
TI  - Skin cooling alters the activation patterns of different heads of the quadriceps.
AB  - The purpose of this study was to examine the effect of selective skin cooling
      over m. vastus lateralis (VL) on the activation patterns of quadriceps femoris
      muscle during knee extension exercise (KEE) using muscle function magnetic
      resonance imaging (mfMRI). The isometric force production of the right thigh was
      tested in 7 healthy young men at maximum voluntary contraction (MVC), and the
      transverse relaxation time (T2) value was taken from mfMR images at rest and
      immediately after KEE with 4 sets of 10 repetitions at a load equal to 60% of
      their 10-rep maximum, with and without skin cooling. The cooling was carried out
      by ice pack on the surface of the skin of the VL for 3 min before resting mfMRI
      and MVC tests, and before KEE, during KEE, and during the KEE rest intervals. The
      percent change in T2 of the m. vastus intermedius was significantly increased by
      skin cooling in comparison to the change without skin cooling, p < 0.05. This
      result suggests that skin cooling alters the activation pattern of the different
      heads of the quadriceps.

PMID- 15981784
TI  - Physical fitness and the metabolic syndrome in adults from the Quebec Family
      Study.
AB  - Physically fit individuals have a lower risk of cardiovascular disease and type 2
      diabetes. However, it is unknown whether the associations between physical
      fitness and the metabolic syndrome are independent of total and abdominal
      adiposity. Physical fitness was defined as the physical work capacity on a cycle
      ergometer at heart rate of 150 bpm (PWC 150) in a sample of 158 men and 198 women
      20-60 years of age. PWC 150 was adjusted for fat-free mass prior to the analyses.
      Percent body fat was estimated by hydrostatic weighing. Visceral and subcutaneous
      abdominal fat were measured by computed tomography. The prevalence of the
      metabolic syndrome was based on two definitions. The metabolic syndrome decreased
      with increasing fitness in men (approx. 6 times higher in less fit vs. most fit
      tertile, p < 0.05) and in women (approx. 4 times higher in less fit vs. most fit
      tertile, p < 0.05). Fitness was negatively associated with most individual
      components of the metabolic syndrome, except HDL-cholesterol for which the
      correlation was positive. However, in men and in women, the effects of physical
      fitness on the individual components of the metabolic syndrome were attenuated
      after considering total and abdominal adiposity.

PMID- 15981785
TI  - Achievement of peak VO2 during a 90-s maximal intensity cycle sprint in
      adolescents.
AB  - The aim of this study was to determine whether peak oxygen uptake (PVO2) attained
      in a 90-s maximal intensity cycle sprint is comparable to that from a
      conventional ramp test. Sixteen participants (13 boys and 3 girls, 14.6 +/- 0.4
      yr) volunteered for the study. On Day 1 they completed a PVO2 test to exhaustion
      using a 25 W x min(-1) ramp protocol beginning at 50 W. Peak VO2 was defined as
      the highest VO2 value achieved, and aerobic power (Wmax) as the power output of
      the final 30 s. On Day 2 the participants completed two 90-s maximal sprints (S1
      and S2). A 45-min recovery period separated each sprint. Mean oxygen uptake over
      the last 10 s of each sprint was determined as PVO2, and minimum power (MinP-30
      s) as the mechanical power attained in the final 30 s. A one-way ANOVA was used
      to analyse differences between S1, S2, and the ramp test for PVO2 and MinP-30 s.
      Peak VO2 was not significantly different between the ramp, S1, or S2 (2.64 +/-
      0.5, 2.49 +/- 0.5, and 2.53 +/- 0.5 L x min(-1), respectively, p > 0.68). The S1
      and S2 PVO2 scores represented 91 +/- 10% and 92 +/- 10% of the ramp aerobic
      test. The MinP-30 s for S1 and S2 were significantly lower than the Wmax of the
      ramp test, p < 0.05. Hence, for researchers solely interested in PVO2 values, a
      shorter but more intensive protocol provides an alternative method to the
      traditional ramp aerobic test.

PMID- 15981786
TI  - Protective effects of moderate exercise with dietary vitamin C and E on blood
      antioxidative defense mechanism in rats with streptozotocin-induced diabetes.
AB  - Daily moderate exercise and supplementation of vitamins C and E (VCE) can be
      beneficial in diabetes by ameliorating the effects of free radical production.
      The present study sought to analyze the effect of moderate exercise accompanying
      VCE supplementation on lipid peroxidation (LP) and antioxidative systems in the
      blood of streptozotocin-induced diabetic rats. Forty female Wistar rats were
      randomly divided 4 groups. The 1st and 2nd groups served as the control and
      diabetic groups, respectively. The 3rd group was the diabetic-exercise group. The
      4th group, also diabetic-exercise rats, received VCE-supplemented feed. Animals
      in the exercised groups were moderately exercised on a treadmill 5 days a week
      for 3 weeks. Diabetes was induced on Day 0 of the exercise. Plasma and red blood
      cell (RBC) samples were taken from all animals on Day 20. Glutathione peroxidase,
      catalase, and reduced glutathione levels in plasma and RBCs, and vitamins A, E,
      and beta-carotene in plasma were lower in diabetic rats than in control animals,
      whereas there was a significant increase in platelet counts in both plasma and
      RBC LP levels. The decreased antioxidant enzymes and vitamins, and the increased
      LP levels and WBC counts, did improve through exercise only, although their
      levels were mostly increased by exercise + VCE supplementation. There were no
      significant changes in the hemoglobin and hematocrit values in the 4 groups. In
      conclusion, these data demonstrate an increase in LP in the blood of diabetic
      animals whereas there was a decrease in the antioxidant vitamins and enzymes.
      However, dietary VCE with moderate exercise may strengthen the antioxidant
      defense system by decreasing reactive oxygen species.

PMID- 15981787
TI  - The effects of moderate, strenuous, and overtraining on oxidative stress markers
      and DNA repair in rat liver.
AB  - Physical exercise above a certain load has been suggested as being a cause of
      oxidative stress. We have tested whether training with moderate (MT), strenuous
      (ST), or over (OT) load can cause alterations in the activities of antioxidant
      enzymes, lipid peroxidation, protein oxidation, DNA damage, or activity of 8-oxoG
      DNA glycosylase (OGG1) in rat liver. The levels of corticosterone decreased in
      all exercising groups but the differences were not significant.
      Adrenocorticotrophin hormone (ACTH) levels decreased, not significantly, in MT
      and OT compared to C. Activity levels of antioxidant enzymes did not change
      significantly in the liver. The levels of reactive carbonyl derivative (RCD)
      content decreased in the liver of exercising animals, and the differences reached
      significance between control and moderately trained groups. The changes in the
      levels of lipid peroxidation (LIPOX) were not significant, but were lower in the
      exercised groups. The 8-hydroxydeoxyguanosine (8-OHdG) levels increased in the OT
      group, and the activity of OGG1 measured from crude cell extracts tended to
      increase in MT and ST. The findings of this study imply that overtraining induces
      oxidative damage to nuclear DNA, but not to liver lipids and proteins.

PMID- 15981788
TI  - Immune alterations, lipid peroxidation, and muscle damage following a hill race.
AB  - Hill races usually include large downhill running sections, which can induce
      significant degrees of muscle damage in a field setting. This study examined the
      link between muscle damage, oxidative stress, and immune perturbations following
      a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous
      blood samples were taken from 7 club level runners before, immediately after, and
      48 hrs postrace. Samples were analysed for total and differential leukocyte
      counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase
      proteins (CRP; fibrinogen; alpha-1-ACT). The total antioxidant status (TEAC) and
      plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha were
      also determined. Subjective pain reports, and plasma activities of CK, MDA, and
      circulatory monocytes reached peak values at 48 hrs postrace (p < 0.05). TEAC and
      the cytokine IL-8 increased immediately after the race (p < 0.05). Plasma TNF
      alpha remained unchanged (p > 0.05). Despite the reports of muscle damage and
      soreness, no evidence of an acute phase response was observed (p > 0.05), which
      may be explained by the failure of the race to induce a plasma TNF-alpha
      response. Future studies should examine the link between muscle damage, oxidative
      stress, and the acute phase response following hill races of longer duration with
      larger eccentric components.

PMID- 15981789
TI  - Effects of pregnancy on maternal work tolerance.
AB  - This review summarizes current information on the tolerance of healthy pregnant
      women and their fetuses to acute strenuous exertion. Maximal aerobic power,
      expressed in L x min(-1), is not significantly affected in women who maintain an
      active lifestyle, whereas values expressed in ml x kg(-1) x min(-1) decline with
      advancing gestational age in relation to maternal/fetal weight gain. Efficiency
      during standard exercise testing and the ventilatory anaerobic threshold (Tvent)
      also appear to be unaffected by pregnancy, but the ability to utilize
      carbohydrate and exercise anaerobically during brief strenuous exercise may be
      reduced. Fetal responses to short strenuous exercise are usually moderate and
      revert to baseline values within approximately 30 min postexercise. Future
      studies should examine alveolar gas exchange kinetics at the start of exercise
      and during recovery from both moderate and strenuous exertion. Existing studies
      of the responses of pregnant women to prolonged exercise have focused primarily
      on substrate utilization and glucose homeostasis. Other maternal responses to
      prolonged exercise that should be examined include acid-base regulation,
      temperature regulation, fluid and electrolyte balance, and perception of effort.
      Fetal reactions should also be examined in relation to maternal responses. Until
      evidence-based, occupation-specific guidelines become available, it is
      recommended that pregnant women use the Joint SOGC/CSEP Clinical Practice
      Guideline: Exercise in Pregnancy and the Postpartum Period, published by the
      Society of Obstetricians and Gynaecologists of Canada and the Canadian Society
      for Exercise Physiology (2003).

PMID- 15981790
TI  - Effects of different types of exercise on body composition and fat distribution
      in HIV-infected patients: a brief review.
AB  - HIV infection and its treatment is associated with unfavourable metabolic and
      morphological abnormalities. These metabolic abnormalities, particularly
      alterations in body composition and fat distribution, may increase the risk for
      cardiovascular and metabolic complications, as well as reduce functional
      independence and lower self-esteem. Thus there is an urgent need to develop
      interventions intended to manage secondary side effects of HIV or antiretroviral
      therapy-related complications. In poly-treated patients, nonpharmacological
      interventions are a logical first step. Exercise training in particular may help
      alleviate some of the metabolic adverse effects associated with antiretroviral
      therapy by favourably altering body composition and patterns of body fat
      distribution. Studies have shown that exercise training, particularly aerobic
      training, can help reduce total body and visceral fat, as well as normalizing
      lipid profiles in HIV-infected patients. The results for resistance training,
      however, are less conclusive. Knowledge of the use of resistance and aerobic
      training and its attendant effects on insulin resistance and adipocytokines may
      represent an effective nonpharmacologic means for treating metabolic
      complications of HIV-infected persons who are receiving appropriate
      antiretroviral therapy. In this brief review we examine the effects of aerobic
      and resistance training on body composition, body fat distribution, and selected
      metabolic outcomes.

PMID- 15981791
TI  - Low levels of recall among adult Canadians of the CSEP/Health Canada physical
      activity guidelines.
AB  - In 1998, Canadian guidelines were released to encourage sedentary adults to
      become more active. Representative surveys of over 4,400 Canadian adults found
      that unprompted recall of these guidelines was low (7.4% in 1999 and 5.2% in
      2002), but was higher among educated, affluent, middle-aged, and the physically
      active. Achieving a high level of activity was associated with demographic
      variables and other information sources, but not with guideline recall. Guideline
      promotion has not reached those most in need.

PMID- 15981792
TI  - A comparison of spaced retrieval to other schedules of practice for people with
      dementia.
AB  - Spaced retrieval training uses a schedule of practice trials distributed
      according to a learner's performance. The authors compared spaced retrieval to
      four alternative schedules of practice to determine whether it is more effective
      than other schedules for people with dementia. Participants practiced (a) pill
      names or (b) nonverbal sequences. Spaced retrieval did not produce long-term
      retention more often than other schedules of practice on either task.
      Participants with higher scores on one portion of the Hopkins Verbal Learning
      Test-Revised were more likely to show long-term retention of pill names
      regardless of schedule of practice (Experiment 1).

PMID- 15981793
TI  - Categorical perception of faces and facial expressions: the age factor.
AB  - Effects of normal aging on categorical perception (CP) of facial identities and
      facial emotional expressions were investigated. The stimuli were morphs of three
      identities and of three expressions. In Experiment 1, 38 healthy participants (22
      to 79 years old; three age groups) had to identify morphed identities (three
      continua) and expressions (three continua) varying with respect to their distance
      from the original photographs. This experiment allowed the computation of the
      boundary between categories (expressions and identities). The results showed that
      the locus of this boundary was not affected by age (except for the continuum
      disgust-happiness), but that the rate of intrusions and latencies of responses
      increased with age. In addition, CP was suggested, as latencies increased as a
      function of the distance between the displayed morph and the original, unmorphed
      photograph. CP predicts an easier discrimination of two morphs located on both
      sides of the boundary than discrimination of two morphs located on the same side.
      This was investigated in Experiment 2 (48 new participants; three age groups).
      For expressions, the prediction was verified in all groups for both accuracy and
      correct latency; in addition, an effect of age was observed only for morphs
      located on both sides of the boundary. For identities, the same pattern of
      results emerged, with one exception: for accuracy, the predicted advantage of
      pairs located on both sides of the boundary was not verified in the oldest group.
      Thus, CP of facial identities seems to vanish with normal aging, whereas CP of
      facial expressions appears to be more robust.

PMID- 15981794
TI  - Aging, encoding, and word retrieval: distinguishing phonological and memory
      processes.
AB  - Word retrieval deficits are one of the most common complaints among older adults.
      The Transmission Deficit Hypothesis predicts that phonologically similar names
      would be harder for older adults to encode and retrieve. Results indicated that
      overall older adults encoded and recalled fewer words than younger adults when
      given only one trial and when given multiple trials to criterion. For both
      experiments, proper names were more difficult to retrieve than common nouns, and
      phonologically similar words were more difficult to retrieve than phonologically
      different words for both older and younger adults. Age differences were not
      evident for retrieving phonologically similar items or names but older adults did
      need more trials to encode phonologically similar items and names. Age
      differences for phonologically similar items and names appear related to encoding
      processes with retrieval of these items consistently hard for both older and
      younger adults.

PMID- 15981795
TI  - Phenomenal characteristics of autobiographical memories for emotional and neutral
      events in older and younger adults.
AB  - The authors investigated age-related differences in phenomenal characteristics of
      autobiographical memories for positive, negative, and neutral events. Younger and
      older participants were asked to recall two specific memories of each type and
      then to rate their memories on several sensorial (e.g., visual, taste) and
      contextual (e.g., location, time) characteristics. The authors found that
      emotional (both positive and negative) memories contained more sensorial and
      contextual details than neutral memories in both age groups, whereas positive and
      negative memories did not differ on most dimensions. In addition, negative
      memories were associated with a higher intensity of positive feelings and a
      reduced complexity of storyline in older as compared to younger adults. These
      results suggest that the effect of emotion on phenomenal characteristics of
      autobiographical memories is similar in younger and older adults, but that older
      adults tend to reappraise negative events in a more positive light than younger
      adults.

PMID- 15981796
TI  - Association of balance measures and perception of fall risk on gait speed: a
      multiple regression analysis.
AB  - Gait speed, commonly modified to adapt to the balance and stability challenges of
      aging, is related to measures of balance and mobility. This study investigated
      associations between age, Berg Balance Scale, Activities-Specific Balance
      Confidence (ABC) Scale, One Question Fear of Falling (1QFOF), and gait speed in
      adults using regression analysis. Results suggested an interaction between 1QFOF
      and ABC scores. An expanded five-variable model explained 49% of gait speed
      variance. Age, ABC, and 1QFOF-ABC interactions were significantly associated with
      gait speed. Regression analysis is useful in investigating associations between
      performance variables and function. Continued research needs to identify optimal
      variable combinations and improve prediction of function.

PMID- 15981797
TI  - Intrapersonal and extrapersonal space: performance of older adults on
      ecologically valid orientation tasks.
AB  - This experiment examined performance of 20 older adults (64 to 76 years) and 20
      young adults (18 to 35 years) on two orientation tasks: The Intrapersonal task
      required participants to point to parts of their body corresponding to those on a
      line drawing; and, the Extrapersonal task involved translating a route indicated
      on paper to walking a route on a corresponding floor map. Older adults were found
      to be slower at completing both tasks, although accuracy of performance was
      comparable between age groups. The results were interpreted in terms of a speed
      accuracy tradeoff that increases with age.

PMID- 15981798
TI  - Hopeful thinking in older adults: back to the future.
AB  - In a sample of 100 community-dwelling older adults (mean age of 76), higher hope
      related to greater life satisfaction and better perceived physical health, but
      hope did not relate to number of illnesses or functional disability. The high
      relative to low-hope participants were more confident of reaching their goals,
      and felt that they were further along in their goal pursuits. The implications of
      these findings are discussed.

PMID- 15981799
TI  - Definition, diagnosis, disease types, and classification of asthma.

PMID- 15981800
TI  - Epidemiology of asthma.

PMID- 15981801
TI  - Pharmacologic control of asthma.

PMID- 15981802
TI  - Classifying "recurrent" breast cancer: lost heterozygosity found.

PMID- 15981803
TI  - Polymorphism in the CD5 gene promoter in B-cell chronic lymphocytic leukemia and
      mantle cell lymphoma.
AB  - Despite the low incidence of microsatellite instability (MSI) in lymphoid
      malignant neoplasms, it has been reported that the CD5 promoter MSI was
      relatively frequent among B-cell chronic lymphoproliferative disorders. We
      studied the presence of MSI in the CD5 promoter in 134 cases of B-cell chronic
      lymphocytic leukemia (B-CLL) and 47 of mantle cell lymphoma (MCL) by comparing
      the pattern of microsatellite repeats on autologous germline and tumor DNA
      samples. Microsatellite alterations were not observed in any case. However, the
      allele distribution of this polymorphism showed a higher frequency of the 18 CA
      allele (0.585) in MCL cases (P = .026; odds ratio [OR], 1.75; 95% confidence
      interval [CI], 1.07-2.87) and of the 19 CA allele (0.179) in B-CLL cases (P =
      .005; OR, 2.26; 95% CI, 1.27-4.01) compared with control cases (0.442 and 0.087,
      respectively). This suggests that although MSI seems not to be involved in the
      pathogenesis of these 2 lymphoid malignant neoplasms, the polymorphic CD5
      promoter is associated with increased susceptibility to these disorders.

PMID- 15981804
TI  - Hodgkin lymphoma involving Waldeyer ring: a clinicopathologic study of 22 cases.
AB  - We report 22 cases of Hodgkin lymphoma involving Waldeyer ring seen at our
      institution during a 31-year interval. There were 16 males (73%) and 6 females
      (27%) with a median age of 48 years (range, 5-81 years), and 15 (68%) patients
      had airway obstruction or tonsillar enlargement. For 19 patients, the clinical
      stage was as follows: I, 7 (32%); II, 11 (50%); and III, 1 (5%). The 3 patients
      (14%) whose disease was unstaged had concurrent or a history of non-Hodgkin
      lymphoma. Histologically, the neoplasms were classified as follows: lymphocyte
      rich classical, 8 (36%); nodular sclerosis, 7 (32%); mixed cellularity, 4 (18%);
      unclassified, 2 (9%); and lymphocyte depletion, 1 (5%). Of 7 stage I cases, 4
      (57%) were the lymphocyte-rich classical type. Reed-Sternberg and Hodgkin cells
      were positive for CD15 and CD30 in 20 cases assessed. Epstein-Barr virus latent
      membrane protein type 1 was positive in 12 (67%) of 18 cases assessed. We
      conclude that Hodgkin lymphoma rarely involves Waldeyer ring, with the lymphocyte
      rich classical type being common at this location.

PMID- 15981805
TI  - The detection and diagnosis of hemoglobin A2' by high-performance liquid
      chromatography.
AB  - Hemoglobin (Hb) A2' is a hematologically silent variant of HbA2 that is detected
      easily by high-performance liquid chromatography (HPLC), where it elutes in the S
      window. Our purposes were to define diagnostic criteria for the HbA2' trait using
      the Variant II (Bio-Rad, Hercules, CA) and to determine the prevalence of HbA2'
      in a metropolitan patient population. All Hb screens (N = 5,862) performed during
      a 26-month period were reviewed for new hemoglobinopathies. We identified 57
      cases of HbA2' trait, making it the fourth most prevalent Hb variant detected in
      this population after HbS, HbC, and beta-thalassemia minor For HbA2' trait cases,
      the mean HbA2 level was 1.7% (SD, 0.17%), and the mean HbA2' level was 1.3% (SD,
      0.18%). Six possible HbA2'/beta-thalassemia double heterozygotes were identified,
      for whom the sum of the HbA2 and HbA2' exceeded 4% of total Hb. Hb variants that
      might interfere with detection of HbA2' include HbS, glycosylated HbC, and HbG2.
      Diagnostic criteria proposed for the HbA2' trait by HPLC are HbA2 of 2% or less,
      S window peak of 1% to 2%, no previous diagnosis of HbS, and absence of HbG and
      HbC.

PMID- 15981806
TI  - Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.
AB  - Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic
      neoplasm) is a recently described entity, with the first case reported in 1994.
      It was suggested initially that the disease originates from NK cells. Since 1994,
      single cases and a few small series have been published. In this review, data
      from the literature and a series of 30 cases from the French and Dutch study
      groups on cutaneous lymphomas are discussed. The major clinical, histopathologic,
      and phenotypic aspects of the disease and diagnostic criteria and data suggesting
      a plasmacytoid dendritic cell origin for the tumor cells are provided.

PMID- 15981807
TI  - Molecular clonality determination of ipsilateral recurrence of invasive breast
      carcinomas after breast-conserving therapy: comparison with clinical and biologic
      factors.
AB  - We established clonality relationships between invasive ipsilateral breast
      failures (IBFs; local recurrences) and initial invasive carcinomas using a
      molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26
      patients treated with breast-conserving therapy for invasive carcinoma with no
      distant metastases (DMs) before the IBE LOH was +/- 50% allelic loss. Eighteen
      IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally
      distinct, second primary carcinomas. IBFs and initial invasive carcinomas were
      morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF
      classification and molecular assay results differed in 11 cases (42%). The mean
      intervals to IBF were 4.7 years in related and 8.7 years in different cases (P =
      .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases,
      the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs
      was 18.9% compared with 7.6% in cases unassociated with DMs (P = .004). Molecular
      assays can accurately establish the clonality of most IBFs. Morphologic
      comparison and clinical IBF classification are unreliable methods of determining
      clonality. Clonally related IBFs occurred sooner than clonally different IBFs.
      Patients with clonally related IBFs are the main pool in which DMs occur Not all
      clonally related IBFs have the same DM association; those with large FAL gains
      were associated with DMs. Molecular clonality assays may provide a reliable means
      of identifying patients who might benefit from systemic chemotherapy at the time
      of IBF.

PMID- 15981808
TI  - Progressive deregulation of the cell cycle with higher tumor grade in the stroma
      of breast phyllodes tumors.
AB  - We studied cell cycle-regulating proteins in phyllodes tumor pathogenesis by
      immunohistochemical analysis for Ki-67, cyclin A, cyclin D1, retinoblastoma
      protein (pRb), p53, p16INK4A, bcl-2, and p21waf1 in the epithelium and stroma of
      40 primary (benign, 21; borderline, 8; malignant, 11) and 7 recurrent tumors of
      different grades. In most cases, the epithelium showed no altered expression of
      cell cycle regulators. Stromal overexpression of p16INK4A, p53, cyclin A, pRb,
      and p21waf1 correlated significantly with tumor grade. The number of altered
      proteins in stroma increased with higher grade and was accompanied by increased
      proliferation. Stromal cyclin A expression was the best separating marker between
      tumor grades. Correlations existed between stromal overexpression of p16NK4A and
      p21waf1, p16INK4A and p53, and p53 and pRb. No immunostaining differences were
      detected between primary tumors and recurrences. Four or more altered proteins
      and p53 expression in the stromal component were independent negative
      prognosticators for disease-free survival. The stromal component of mammary
      phyllodes tumors displays an increasing level of cell cycle deregulation with
      higher tumor grade; the epithelial compartment mostly remains inconspicuous.
      Several combinations of aberrantly expressed cell cycle proteins seem important
      in the stromal progression of phyllodes tumors. The number of stromal cell cycle
      aberrations and stromal p53 expression might predict clinical behavior.

PMID- 15981810
TI  - Analysis of lymph nodal metastases in malignant melanoma using the poisson
      probability paradigm and Bayes rule.
AB  - This article deals with and formalizes 2 notions common to the practice of
      pathology. The first is that the number of lymph nodes found positive for
      metastasis relates directly to the total number of lymph nodes examined. The
      second is that for any patient, there is a chance that the absence of lymph node
      metastases is a false-negative result. I introduce the Poisson probability
      density function to deal with the first notion and the Bayes probability rule to
      deal with the second. To illustrate the insight these 2 models provide, I apply
      them to data regarding lymph nodal metastases in malignant melanoma. In this
      preliminary study, the results of these 2 models correlate well with observed
      survival probabilities in patients with stage N0 melanoma and with observed rates
      of false-negative results in sentinel lymph node biopsy technology. With further
      development, the combination of these models should provide a way to estimate the
      probability of nodal metastasis when, in fact, none have been observed. Thus,
      these models might provide useful tools for evaluating patients with stage N0
      malignant neoplasms.

PMID- 15981809
TI  - Histologic and immunohistochemical characteristics of neoplastic and
      nonneoplastic subgroups of atypical squamous lesions of the uterine cervix.
AB  - Atypical squamous lesion (ASL), a histologic diagnosis of unclear significance in
      the uterine cervix, can be divided into neoplastic and nonneoplastic groups. We
      aimed to determine the morphologic characteristics of these 2 groups. Histologic
      and immunohistochemical features were evaluated on the original biopsy specimen
      from 37 ASL cases, and the results were compared between neoplastic (19 cases)
      and nonneoplastic (18 cases) groups, which were determined based on the follow-up
      histopathologic findings. Mitosis, vertical nuclear growth pattern, no
      perinuclear halo, indistinct cytoplasmic border, primitive cells in the upper
      third of the squamous layer, p16+ cells in the upper two thirds of the squamous
      layer, and Ki-67+ cells in the upper two thirds of the squamous layer were
      significant indicators for neoplastic ASLs. Of the 19 neoplastic ASLs, 16 (84%)
      had 5 or more of these 7 indicators. The majority (16/18 [89%]) of the
      nonneoplastic ASLs had 2 or fewer indicators. Determination of the histologic and
      immunohistochemical characteristics is useful for distinguishing neoplastic and
      nonneoplastic ASLs.

PMID- 15981811
TI  - High-throughput cervical cancer screening using intracellular human
      papillomavirus E6 and E7 mRNA quantification by flow cytometry.
AB  - The Papanicolaou (Pap) test, based solely on the morphologic examination of
      exfoliated cells from the cervix, has reduced deaths due to cervical cancer by
      74% in the United States during the past 40 years. During that time, the
      molecular mechanisms of cervical cancer have largely been elucidated. Taken
      together, these observations have identified a need for a high-throughput
      cervical cancer screening assay. We report the development of a high-throughput
      assay consisting of simultaneous immunophenotyping and ultrasensitive in situ
      hybridization for human papillomavirus (HPV) E6 and E7 messenger RNA (mRNA). This
      assay can be performed in less than 3 hours directly from liquid-based cervical
      cytology specimens. Overall, HPV fluorescence in situ hybridization (FISH) for E6
      and E7 mRNA demonstrated 83.3% sensitivity and 91.3% specificity for high-grade
      squamous intraepithelial lesions compared with the Pap test in 231 liquid-based
      cytology samples from 2 cohorts. In a subset of these samples, HPV FISH
      demonstrated higher sensitivity and specificity than Hybrid Capture (Digene,
      Gaithersburg, MD) for high-risk genotypes.

PMID- 15981812
TI  - Malignant peritoneal mesothelioma in women: a study of 75 cases with emphasis on
      their morphologic spectrum and differential diagnosis.
AB  - Seventy-five malignant mesotheliomas of the peritoneum in women were reviewed to
      highlight their morphologic spectrum. The patients ranged from 17 to 92 (mean,
      47.4) years of age. The clinical presentation was usually abdominal or pelvic
      pain, abdominal swelling (sometimes due to ascites), or a pelvic mass. On
      microscopic examination, the majority of the tumors had only an epithelial
      morphology, but 4 were biphasic and 1 was sarcomatoid. The most common epithelial
      patterns were tubular and papillary (which often coexisted), but 5 tumors were
      purely diffuse; 2 had cells with abundant glassy eosinophilic cytoplasm (so
      called deciduoid mesothelioma). The cells in the tubular and papillary patterns
      were generally cuboidal with scant to moderate amounts of eosinophilic cytoplasm.
      Nuclear atypia was usually only mild, although a minority of cases had moderate
      or even, occasionally, severe atypia. Many tumors had foci that, viewed in
      isolation, resembled so-called well-differentiated papillary mesothelioma, and
      accordingly that diagnosis should be made cautiously. Unusual features were
      lymphoid follicles (13 cases), striking myxoid stroma (5 cases), prominent foamy
      histiocytes (5 cases), and a striking vascular proliferation (1 case). The varied
      morphology of peritoneal malignant mesotheliomas may raise a broad differential
      diagnosis, but in most cases the resemblance to other tumors is limited.
      Histochemistry, immunohistochemistry, and electron microscopy may provide
      important aid, particularly when tissue is limited, but should be needed only
      occasionally.

PMID- 15981813
TI  - Clinical significance of unsatisfactory conventional pap smears owing to
      inadequate squamous cellularity defined by the Bethesda 2001 criterion.
AB  - To determine the incidence of clinically significant lesions in long-term follow
      up after a diagnosis of inadequate squamous cellularity using former and new
      criteria, we reviewed conventional Papanicolaou (Pap) smears (January-December
      1998) for adequacy based on the Bethesda System 2001 criterion. Of 23,302 Pap
      smears evaluated in our laboratory, 114 (0.489%) were classified as
      unsatisfactory and 245 (1.051%) as "satisfactory but limited by" based on the 10%
      rule. Follow-up information for 5 years was obtained for 172 patients without a
      concurrent cervical epithelial abnormality: 25 (14.5%) had squamous abnormalities
      (atypical squamous cells, 22; low-grade squamous intraepithelial lesion, 2; and
      high-grade squamous intraepithelial lesion, 1). With the Bethesda System 2001
      criterion, 167 (97.1%) of 172 smears had inadequate squamous cellularity and 5
      (2.9%) were adequate. No differences in the incidence of squamous abnormalities
      detected on follow-up were noted between patients with unsatisfactory Pap smears
      owing to inadequate squamous cellularity and patients with satisfactory and
      negative smears. Our findings raise the question whether patients with
      unsatisfactory Pap smears and a negative history of gynecologic diseases require
      repeated Pap smears within 2 to 4 months as suggested by the American Society for
      Colposcopy and Cervical Pathology guideline.

PMID- 15981814
TI  - Characterization of chromosome 14 abnormalities by interphase in situ
      hybridization and comparative genomic hybridization in 124 meningiomas:
      correlation with clinical, histopathologic, and prognostic features.
AB  - We analyzed quantitative chromosome 14 abnormalities in 124 meningiomas by
      interphase fluorescence in situ hybridization (iFISH) and confirmed the nature of
      abnormalities by comparative genomic hybridization (CGH). We correlated the
      abnormalities with clinical, histopathologic, and prognostic factors. Of 124
      cases, 50 (40.3%) showed loss (14.5%) or gain (25.8%) of the 14q32 chromosome
      region by iFISH. Most corresponded to numeric abnormalities: monosomy (12.9%),
      trisomy (1.6%), or tetrasomy (24.2%); in only 2 cases (1.6%), chromosome 14 loss
      did not involve the whole chromosome and was restricted to the 14q31-q32 region
      (confirmed by CGH). Cases with gain or monosomy corresponded more frequently to
      histologically malignant tumors (P = .009). Patients with monosomy 14/14q-, but
      not those with gain, more often were male (P = .04) and had a greater incidence
      of recurrence (P = .003) and shorter relapse-free survival (P = .03). The 2
      patients with loss limited to 14q31-q32 had histologically benign tumors and no
      relapse after more than 5 years' follow-up. Most meningiomas with chromosome 14
      abnormalities have numeric changes, with interstitial deletions of 14q31-q32
      present in few cases. Of the abnormalities detected, only monosomy 14 showed an
      adverse prognostic impact.

PMID- 15981815
TI  - Multitarget FISH and LOH analyses at chromosome 3p in non-small cell lung cancer
      and adjacent bronchial epithelium.
AB  - Multitarget fluorescence in situ hybridization (FISH; LAVysion, Vysis, Downers
      Grove, IL) targeting chromosomes 6p11-q11, 7p12, 8q24, and 5p15.2 was compared
      with results of microsatellite studies at chromosome 3p to identify molecular
      changes associated with tobacco use and tumor development in non-small cell lung
      cancer (NSCLC). Analyses were performed on 26 NSCLCs and matched benign bronchial
      epithelium; samples from 10 patients without NSCLC served as control samples.
      Significant molecular differences between tumor tissue and corresponding benign
      bronchi were found using FISH (P = .001) and loss of heterozygosity (LOH)
      analysis (P = .031). Bronchial epithelium from patients with NSCLC was
      genetically different from epithelium from patients without NSCLC in FISH
      analysis (P = .025). Receiver operating characteristic curve analysis revealed an
      optimal cutoff value of 5% atypical cells for bronchial epithelium. There was no
      statistical correlation with the patient's smoking history, and LOH analysis of
      bronchi did not differentiate between patients with and without NSCLC. Multicolor
      FISH analysis is able to detect a tumor-associated molecular field effect in
      bronchi adjacent to NSCLC.

PMID- 15981816
TI  - Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) of the lung:
      a clinicopathologic and immunohistochemical study of two cases.
AB  - Two cases of primary angiolymphoid hyperplasia with eosinophilia (epithelioid
      hemangioma) (ALHE/EH) of the lung are described. Both patients are white, a 60
      year-old man and a 27-year-old woman. One patient had a long-standing history of
      asthma, and the other had symptomatology related to the pulmonary mass. Wedge
      resections were performed in both cases, and both lesions shared similar
      histopathologic changes, mainly the presence of a tumor mass with a marked
      presence of eosinophils in the background, lymphoid hyperplasia, and marked
      proliferations of small-caliber vessels. Immunohistochemical studies using
      leukocyte common antigen, L-26, and UCHL-1 nicely stained the lymphoid component
      of the lesion, and CD31 clearly outlined the vascular component of the process.
      Clinical follow-up demonstrated that the woman died of status asthmaticus, and
      the man was alive and well 1 year after surgical resection of the lesion. Both
      cases highlight the ubiquitous distribution of ALHE/EH and underscore the
      importance of keeping these lesions in the differential diagnosis of vascular and
      lymphoid lesions of the lung.

PMID- 15981817
TI  - Comparison of immunohistochemical and fluorescence in situ hybridization
      assessment of HER-2 status in routine practice.
AB  - Because HER-2 expression in invasive carcinoma of the breast has well-documented
      ramifications for treatment and prognosis, accurate assessment of HER-2 status is
      critical. Comparative studies have shown high concordance rates between
      immunohistochemical analysis and fluorescence in situ hybridization (FISH) in
      cases with immunohistochemical scores of 0 or 1+ (negative) and 3+ (strongly
      positive) and low concordance rates among cases with immunohistochemical scores
      of 2+. The present study was performed to determine concordance rates in a
      setting more representative of routine clinical practice, in which multiple
      pathologists submit specimens to a single cytogenetics referral laboratory. We
      found a higher rate of discordance between immunohistochemical analysis and FISH
      (approximately 92%) in the groups with immunohistochemical scores of 2+ than
      reported in other studies. These results strongly support the practice of
      performing FISH in all cases with immunohistochemical scores of 2+, particularly
      in routine practice, in which interobserver variability in immunohistochemical
      scoring among multiple pathologists is likely to be high.

PMID- 15981818
TI  - Platelet dysfunction in primary thrombocythemia using the platelet function
      analyzer, PFA-100.
AB  - We measured platelet function by standard aggregometric tests and by the PFA-100
      (Dade Behring, Newark, DE) in samples from 55 patients with primary
      thrombocythemia (PT) and 26 healthy volunteers. Platelet function was evaluated
      in platelet-rich plasma by aggregation tests. PFA-100 studies (closure time) were
      performed in citrated whole blood using collagen-adenosine diphosphate (ADP) and
      collagen-epinephrine cartridges. Plasma levels of von Willebrand factor (vWF)
      also were measured. The mean +/- SD closure time for patients vs volunteers for
      the collagen-epinephrine cartridge was prolonged (210.8 +/- 62.2 vs 118.1 +/-
      19.6 seconds; P < .001); results were abnormal for 38 patients (69%). Results
      with the collagen-ADP cartridge also were abnormal in patients (134.3 +/- 58.4
      seconds) vs volunteers (87.3 +/- 15.6 seconds; P < .001); closure time was
      prolonged in 23 patients (42%). A decreased response to epinephrine (38.4% +/-
      34.2% vs 82.5% +/- 10.3%; P < .001), the main defect detected by platelet
      aggregation tests, affected 32 patients (58%). Platelet response to collagen also
      was abnormal (52.0% +/- 34.6% vs 86.0% +/- 10.1%; P < .01) but affected only 21
      patients (38%). vWF levels for patients were normal. The results seem to confirm
      that platelet function in patients with PT is abnormal and show that platelet
      function can be assessed by an easy, reproducible, and sensitive method, the PFA
      100. Closure time usually was prolonged; this feature could be applied in the
      diagnosis of PT.

PMID- 15981819
TI  - Protein S assays: an analysis of North American Specialized Coagulation
      Laboratory Association proficiency testing.
AB  - To assess current laboratory practice and the performance of different reagent
      instrument combinations for protein S testing, protein S results from the North
      American Specialized Coagulation Laboratory Association (NASCOLA) proficiency
      testing surveys for 2002 and the first half of 2003 were analyzed. A written
      survey of NASCOLA laboratories also was performed to further assess current
      laboratory practices for protein S testing. The free protein S antigen assays and
      the Diagnostica Stago Staclot protein S assay were extremely accurate in
      detecting a heterozygous type I protein S deficiency. Another functional protein
      S assay and most total protein S assays were less reliable, depending to some
      extent on the instrument. All assays used by NASCOLA laboratories appropriately
      identified normal protein S specimens. NASCOLA laboratories performed at least as
      well as European Concerted Action on Thrombosis laboratories in the proficiency
      tests. The results suggest that the diagnosis of heterozygous protein S
      deficiency may be problematic with some currently available assays. Many total
      protein S antigen assays do not add to the diagnosis and can be unreliable for
      protein S deficiency subtyping. Better standardization of functional and
      antigenic assays is needed.

PMID- 15981820
TI  - It's a small, small world.

PMID- 15981821
TI  - E-cadherin negative primary small cell carcinoma of the breast.

PMID- 15981822
TI  - Monitor demands Ofcom-style single regulator for health.

PMID- 15981823
TI  - Beds and Herts fase tough cuts.

PMID- 15981824
TI  - Reform research. Home truths for the DoH as the service tells it straight.

PMID- 15981825
TI  - On deficit by design.

PMID- 15981826
TI  - Atlantic drift. Interview by Andy Cowper.

PMID- 15981827
TI  - Data briefing. Variation in lengths of stay.

PMID- 15981828
TI  - Primary care. Ringing the changes.
AB  - A 2000 DoH review called for out-of-hours services to be straightforward for
      users to access, and for service planning to involve multi-disciplinary co
      operation from health professionals. Out-of-hours provision has evolved since
      then, but missed targets, insufficient staff numbers and inequalities between
      different providers continue to hamper progress.

PMID- 15981829
TI  - On public health.

PMID- 15981830
TI  - On clinical management. Many medical directors, like harlots, have power without
      responsibility.

PMID- 15981831
TI  - Regulation. Boards on the wards.

PMID- 15981832
TI  - Foundation trusts. Count the cost.

PMID- 15981833
TI  - Child protection. Children first.

PMID- 15981834
TI  - Harassment. Bully for you.

PMID- 15981835
TI  - Purchasing. The gang way.

PMID- 15981836
TI  - Regional focus: Midlands. Move over Rover.

PMID- 15981837
TI  - Training. 20/20 supervision.

PMID- 15981838
TI  - Education. Degree of certainty.

PMID- 15981840
TI  - [Nutritional assessment of the severely ill patient].
AB  - There are different parameters aimed at assessing nutritional status. These
      parameters may be of some help to assess nutritional status prior to patients'
      admission. However, their application in the critically ill patient is
      troublesome since results interpretation is interfered by changes originated by
      the acute disease or treatment measures. This is particularly true in relation to
      anthropometrical variables that are severely affected by changes in water
      distribution in the critical patient. Biochemical markers (creatinine/height
      index, serum albumin, etc.) are also interfered as a result of the metabolic
      changes that modify the synthesis and degradation processes. Short half-life
      proteins (prealbumin, retinol-bound protein) are not indicative of the
      nutritional status although they do inform about an appropriate response to
      nutrients intake and concurrence of new conditions of metabolic stress.
      Functional assessment parameters, such as muscular function test, are also
      difficult to apply in a great number of patients. Subjective global assessment,
      although it requires some degree of expertise, may be an appropriate tool. Some
      theoretically more accurate methods, such as bioelectrical impedance, need
      further investigation in these patients before being recommended.

PMID- 15981839
TI  - [Recommendations for nutritional assessment and specialized nutritional support
      of critically ill patients].
AB  - Due to the characteristics of critically ill patients, elaborating
      recommendations on nutritional support for these patients is difficult. Usually
      the time of onset of nutritional support or its features are not well
      established, so that its application is based on experts' opinion. In the present
      document, recommendations formulated by the Metabolism and Nutrition Working
      Group of the Spanish Society of Intensive and Critical Medicine and Coronary
      Units (SEMICYUC) are presented. Recommendations are based on the literature
      analysis and further discussion by the working group members in order to define,
      consensually, the more relevant issues of metabolic and nutritional support of
      patients in a critical condition. Several clinical situations have been
      considered which are developed in the following articles of this publication. The
      present recommendations aim at providing a guideline for the less experienced
      clinicians when considering the metabolic and nutritional issues of critically
      ill patients.

PMID- 15981841
TI  - [Nutritional support in the critically ill patient: to whom, how, and when?].
AB  - Existing data about indication and time of onset of nutritional support are not
      homogeneous. However, the presence of a deterioration of the nutritional status
      is accompanied by harmful effects so that, broadly speaking, specialized
      nutritional support onset would be advisable if a fasting period longer than 5-7
      days is foreseen. Parenteral nutrition routinely administered to critically ill
      patients may increase their morbidity and mortality. Whenever possible, enteral
      nutrition should be the preferred route of nutrients intake since it has been
      shown to have a favorable effect on infectious complications rates. Enteral
      nutrition should be started early on (within the first 36 hours of admission).
      Although transpyloric nutrients administration may however reduce
      bronchoaspiration and increase the diet effective volume received by patients,
      there are no data for recommending routinary usage of the transpyloric route for
      nutritional support in the critically ill patients.

PMID- 15981842
TI  - [Requeriments of macronutrients and micronutrients].
AB  - Critically ill patients have important modifications in their energetic
      requirements, in which the clinical situation, treatment applied and the time
      course take part. Thus, the most appropriate method to calculate the caloric
      intake is indirect calorimetry. When this test is not available, calculations
      such as Harris-Benedict's may be used, although not using the so high correction
      factors as previously recommended in order to avoid hypercaloric intakes. The
      intake of a fixed caloric amount (comprised between 25-30 KcalKg/min) is adequate
      for most critically ill patients. Carbohydrates intake must be of 5 g/kg/day)
      maximum. Glucose plasma levels must be controlled in order to avoid
      hyperglycemia. With regards to fat intake, the maximum limit should be 1.5
      g/kg/day. The recommended protein intake is 1.0-1.5 g/kg/day, according to the
      clinical situation characteristics. Special care must be taken with
      micronutrients intake, an issue that is many times undervalued. In this sense,
      there are data to consider some micronutrients such as Zn, CU, Mn, Cr, Se, Mo and
      some vitamins (A, B, C, and E) of great importance for patients in a critical
      condition, although specific requirements for each one of them have not been
      established.

PMID- 15981843
TI  - [Artificial nutrition in acute renal failure].
AB  - Nutritional support in critically ill patients that present with acute renal
      failure has been a matter of change in recent years. This is due to the
      increasing and earlier use of extrarenal depuration techniques. Modifications in
      nutritional and metabolic support regimen aimed at preventing renal failure
      progression, classically recommended, would not have an indication in these
      situations but in cases not treated with one of these depurative techniques.
      Thus, protein intake should be appropriate to the clinical situation, and
      formulations compounded exclusively by essential amino acids are no longer
      recommended. Glucose administration should not be different from that recommended
      in other conditions. Lipids infusion should have a maximum limit of 1 g/kg/day.
      Thus, the use of standard diets is not problematic in patients treated with
      depurative techniques. However, the relationship between substrates flow through
      dialysis membranes and its effect on nutrients demands has not been fully
      established yet. It is likely that an increase in nutrients intake may be
      necessary to counteract the obliged loss by depurative techniques. The other way
      around, the role of these techniques as an appropriate way for nutritional
      support in critically ill patients remains to be studied.

PMID- 15981844
TI  - [Artificial nutrition in liver failure].
AB  - Nutritional and metabolic support in patients with liver failure should be able
      to adequately provide the nutritional requirements and, at the same time, to
      contribute in patients' recovery by controlling or reverting the metabolic
      impairments observed. However, in spite of the pathophysiologic basis described
      by some authors considering amino acids unbalance as a triggering and maintaining
      factor for encephalopathy, there are no sufficient data to recommend the use of
      "specific" solutions (branched amino acids-enriched and low on aromatic amino
      acids) as part of the nutritional support of patients with acute liver failure.
      Its routinary use is neither recommended for preventing complications in patients
      submitted to liver transplantation. As with other critically ill patients, the
      nutrients administration route should be the enteral route, whenever possible.
      The use of "liver failure" specific diets is not recommended; on the contrary,
      nutrients composition must be adapted to the metabolic stress condition. In
      patients requiring parenteral nutrition, there is no contraindication to the use
      of lipid infusions. An increase in vitamins and micronutrients intake is
      recommended. In patients submitted to liver transplantation, nutrients intake
      should be started early in the postoperative period through a transpyloric route
      of access.

PMID- 15981845
TI  - [Artificial nutrition in acute pancreatitis].
AB  - Metabolic changes that occur in acute pancreatitis result, as with other
      critically ill patients, in a metabolic stress situation that many times requires
      the application of a specialized nutritional support. Patients presenting the
      highest severity indexes (defined as Ranson's index = 3 or an APACHE II = 10) are
      candidates to receive nutritional support. Enteral nutrition must be the first
      route to consider for nutrients supply and must be maintained except for patients
      that have intolerance or develop pain, ascites, or increased serum amylase
      levels. Transpyloric enteral nutrition, through a naso-jejunal tube or by means
      of a jejunostomy catheter, is a safe access in severe acute pancreatitis, and it
      may even be accompanied by advantages in the patients' clinical course as
      compared with parenteral nutrition. The indication for parenteral nutrition would
      be conditioned by the inability to obtain an appropriate enteral (jejunal)
      approach, intolerance to enteral nutrition, or disease exacerbation after the
      onset of enteral nutrition support. With current data, no recommendations can be
      established in relation to the ideal characteristics that nutrients composition
      received by acute pancreatitis patients should meet.

PMID- 15981846
TI  - [Artificial nutrition in respiratory failure].
AB  - Patients with chronic respiratory failure frequently have nutritional impairments
      that prompt nutritional support. This is more important during acute exacerbation
      episodes since, in this situation, the risk for hyponutrition is increased and
      recovery may be compromised. In order to prevent ventilatory overload,
      nutritional support should be normocaloric or mildly hypocaloric (using indirect
      calorimetry, if possible) with a fat content ratio of around 50% of the caloric
      intake. Micronutrients supply should be considered due to the effects of some of
      them (P, Mg, Se) on respiratory function. The aim of nutritional support in
      patients with acute respiratory failure (ARDS) is the requirements provision
      meanwhile the inflammatory response is modulated and repair mechanisms against
      acute damage are stimulated. Qualitative modification of lipids supply (by
      decreasing the intake of linoleic acid and increasing other eicosanoids-precursor
      lipids with a lesser inflammatory capability) and the use of antioxidants seem to
      be the most important mechanisms in this regard.

PMID- 15981847
TI  - [Artificial nutrition in intestinal failure: short bowel syndrome. Inflammatory
      Bowel Disease].
AB  - Large intestinal resection produces a sufficient number of impairments as to
      require specialized nutritional support. Basic treatment measures, especially
      during the acute phase after intestinal resection or in the presence of severe
      complications in patients with short bowel syndrome, include fluid and
      electrolytes reposition and nutritional support implementation in order to
      prevent hyponutrition. Enteral nutrition is the main stimulating factor for
      adaptation of the remaining bowel. However, its application has some difficulties
      during the acute phase, and thus patients must be frequently treated with
      parenteral nutrition. The presence of hyponutrition may be also important in
      patients with intestinal inflammatory disease. Nutritional support is indicated
      in these cases as the primary treatment modality for the disease, as
      hyponutrition treatment, or as perioperative treatment in patients needing
      surgery. In spite of the digestive pathology, there are data to recommend enteral
      nutrition as the initial method for nutrients provision in patients that need it.

PMID- 15981848
TI  - [Artificial nutrition in hyperglycemia and diabetes mellitus in critically ill
      patients].
AB  - The need to strictly control glucose levels, even in nondiabetic patients, has
      recently emerged following the publication of the results that indicate the
      possibility of reducing the morbidity and mortality in critically ill patients.
      Since hyperglycemia is one of the most frequent metabolic impairments in these
      patients, insulin therapy is a necessity in most of the cases. In order to
      prevent hyperglycemia and its associated complications, nutritional support must
      be adjusted to the patient's requirements, avoiding hyponutrition. Whenever
      possible, nutrients supply should be done through the digestive route. Parenteral
      nutrition is more often accompanied by hyperglycemia and requires an increase in
      insulin dosage to control it. There are two types of enteral diets designed to
      help controlling hyperglycemic conditions: carbohydrates rich diets, and fat rich
      diets. In general terms, carbohydrates rich diets may be recommended in type 1
      diabetic patients who are in a stable condition, and fat rich diets in type 2
      diabetes and in stress hyperglycemia. In both cases, the use of low glycemic
      index carbohydrates is recommended. Protein intake should be adjusted to the
      patients' metabolic stress level. In diabetic patients with acute disease, an
      increase in antioxidants intake is recommended.

PMID- 15981849
TI  - [Nutritional support in the patient with GI malignancy].
AB  - Hyponutrition is a common feature of patients with GI malignancy. When these
      patients reach a critical situation, such as the postoperative period of a tumor
      resection or after a surgery for the presence of complications, nutritional
      status further deteriorates. Nutritional intervention should be part of the
      therapeutic process, starting at the preoperative phase in malnourished patients.
      Enteral nutrition is the route of choice for nutrients supply, although insertion
      of enteral tubes during the surgical procedure may need to be considered many
      times. Enteral nutrition is a safe technique in these patients and may even
      represent some advantages in their clinical course as compared to parenteral
      nutrition. The use of pharmaco-nutrients-enriched diets brings beneficial effects
      (decrease of infectious complications and hospital stay) to patients, although a
      favorable effect on mortality cannot be demonstrated.

PMID- 15981850
TI  - [Nutritional support in aids patients].
AB  - Advances in HIV infected patients' treatment have modified their prognosis,
      making possible to consider their admission to the ICU for acute complications.
      HIV infected patients show nutritional impairments onto which changes due to
      acute disease are added. Thus, they are candidate to receive specialized
      nutritional support. The enteral route should be preferred for nutrients supply
      in case of necessary. With regards to nutritional support characteristics, it
      should be adapted to the metabolic situation, similarly to what is recommended
      for other diseases. It has not been demonstrated that the use of substrates with
      a pharmaco-nutrient capability (glutamine or arginine supplements or
      modifications in the lipidic component quality) will improve the immunological
      condition or the clinical curse of patients with HIV infection/AIDS.

PMID- 15981851
TI  - [Nutritional support in burnt patients].
AB  - Thermal injury leads to a hypermetabolic response which magnitude is among the
      highest that critically ill patients may present. The energetic waste should be
      measured by indirect calorimetry in burnt patients. When this test is lacking,
      published calculations to estimate the energetic waste are useful in these
      patients. Nutritional therapy in burnt patients should be started early and
      through the enteral route whenever possible. Total caloric intake is higher than
      that recommended for other critically ill patients, but should not be higher than
      200% of basal energetic waste. Also recommended is a higher hyperproteic intake
      than that suggested for other situations. With regards to the use of nutrient
      substrates, there are data to recommend the use of pharmaco-nutrients, such as
      arginine and glutamine, in burnt patients. In order to stimulate wound healing,
      it is also recommended to administer vitamin A, vitamin C and zinc supplements.

PMID- 15981852
TI  - [Nutritional support in polytraumatized patients].
AB  - Polytraumatism usually presents in previously healthy patients with a good
      nutritional status. However, metabolic changes derived from the traumatic injury
      put these patients in a nutritional risk situation. Specialized nutritional
      support should be started if it is foreseeable that nutritional requirements will
      not be met p.o. within the 5-10 days period from admission. Enteral nutrition
      should be the first route to consider for nutrients intake. However, the presence
      of head trauma leads to gastrointestinal motility impairments that hinder
      tolerance to enteral nutrition. Patients with abdominal trauma also present
      difficulties for the onset and tolerance of enteral diet. The insertion of
      transpyloric tubes or jejunostomy catheters allows early use of enteral nutrition
      in these patients.

PMID- 15981853
TI  - [Nutritional support in sepsis].
AB  - Although it is considered that metabolic and nutritional support must be part of
      the management of septic patients, it has not been conclusively shown that
      nutritional support will improve survival or complications from sepsis. Specific
      data on this issue are scarce since there are few studies that have investigated
      specialized nutritional support in septic patients. Thus, most of the
      recommendations are based on outcomes obtained in severely ill patients with
      different pathologies. It is assumed that nutritional support should be carried
      out through the enteral route whenever possible, as in other critically ill
      patients. The energetic waste in these patients is highly variable, although in
      general terms the hypermetabolic situation may be classified as moderate. An
      adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation
      to calculate the caloric intake. Septic patients should receive a hyperproteic
      intake. The amount of glucose administered should not exceed 70% of non-protein
      calories, and lipids intake should not exceed 40%. With regards to
      micronutrients, it is recommended to increase the supply of those with
      antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are
      data to consider that the use of diets enriched with pharmaco-nutrients (both
      with parenteral and enteral routes) may be beneficial in septic patients,
      although there is some controversy when interpreting the outcomes.

PMID- 15981854
TI  - [Artificial nutrition in hematopoietic stem cells transplantation].
AB  - Patients submitted to hematopoietic stem cells transplantation (HSCT) have an
      increased risk for having hyponutrition, both in the phase prior to
      transplantation and after this one. The indication of specialized nutritional
      support is common in allogenic HSCT, whereas patients submitted to auto-HSCT need
      it in the presence of complications that compromise an adequate nutrients intake.
      Enteral nutrition through a nasogastric tube has difficulties in these patients;
      the presence of mucositis delays the indication for enteral nutrition, which
      usually is poorly tolerated. Thus, frequently parenteral nutrition needs to be
      used as the route for nutritional support. The use of specific substrates, such
      as glutamine, is a controversial issue.

PMID- 15981855
TI  - Pierre-Francois Olive Rayer: biography.

PMID- 15981856
TI  - The history of albuminous nephritis. 1840.

PMID- 15981857
TI  - Mitral valve function and chordal force distribution using a flexible annulus
      model: an in vitro study.
AB  - Since variations in annular motion/shape and papillary muscle displacement have
      been observed in studies of dilated cardiomyopathy and ischemic mitral
      regurgitation, the objective of this study was to investigate the effects of
      annular motion/flexibility and papillary muscle displacement on chordal force and
      mitral valve function. Six human mitral valves were studied in a left heart
      simulator using a flexible annular model. Mitral flow, trans-mitral pressure and
      chordae tendineae tension were monitored online in normal and pathophysiologic
      papillary muscle positions. The flexible annulus model showed a significant
      increase in mitral regurgitation volume (p < 0.05) when compared to static annuli
      models. Furthermore, there was a significant increase of force on the basal
      chords compared to the force present with the static annuli models. Utilizing the
      flexible annulus model, papillary muscle displacement significantly increased the
      force on the anterior strut, posterior intermediate and commissural chords. (1)
      Papillary muscle displacement increases the tension on the intermediate chords
      inducing tenting of the leaflets and subsequent regurgitation. (2) The tension on
      the intermediate and marginal chords is relatively insensitive to annular motion,
      whereas tension on the basal chords is directly affected by annular motion.

PMID- 15981858
TI  - Fluid-structure coupled CFD simulation of the left ventricular flow during
      filling phase.
AB  - The fluid-structure coupled simulation of the heart, though at its developing
      stage, has shown great prospect in heart function investigations and clinical
      applications. The purpose of this paper is to verify a commercial software based
      fluid-structure interaction scheme for the left ventricular filling. The scheme
      applies the finite volume method to discretize the arbitrary Lagrangian-Eulerian
      formulation of the Navier-Stokes equations for the fluid while using the
      nonlinear finite element method to model the structure. The coupling of the fluid
      and structure is implemented by combining the fluid and structure equations as a
      unified system and solving it simultaneously at every time step. The left
      ventricular filling flow in a three-dimensional ellipsoidal thin-wall model
      geometry of the human heart is simulated, based on a prescribed time-varying
      Young's modulus. The coupling converges smoothly though the deformation is very
      large. The pressure-volume relation of the model ventricle, the spatial and
      temporal distributions of pressure, transient velocity vectors as well as vortex
      patterns are analyzed, and they agree qualitatively and quantitatively well with
      the existing data. This preliminary study has verified the feasibility of the
      scheme and shown the possibility to simulate the left ventricular flow in a more
      realistic way by adding a myocardial constitutive law into the model and using a
      more realistic heart geometry.

PMID- 15981859
TI  - Bistability and correlation with arrhythmogenesis in a model of the right atrium.
AB  - Rapid pacing is an important tool for understanding cardiac arrhythmias. A recent
      experiment involving rapid pacing of sheep atria indicated that the initiation of
      atrial arrhythmias may be related to the 1:1/2:1 bistability. To elucidate the
      mechanism of this relation, this study applied the pacing protocol from the sheep
      study to an idealized model of the right atrium. The model included all major
      anatomical features, the sino-atrial node, and the regional differences in the
      action potential duration (APD). A pacing protocol was applied, in which the
      basic cycle length (BCL) was decreased in steps of 10 ms until the response
      switched to 2:1, then BCL was increased. The 1:1-to-2:1 transitions occurred at
      shorter BCLs than the 2:1-to-1:1 transitions yielding a global bistability window
      of 60ms. As in the sheep study, idiopathic waves were observed at BCLs within or
      near the bistability window. The model was used to quantify the types,
      prevalence, and persistence of idiopatic waves, study their initiation and
      termination, and relate them to the model components. The results demonstrate
      that idiopatic waveforms move with the shift of the bistability window and that
      they disappear when bistability is eliminated. Thus, this modeling study supports
      causal relationship between the 1:1/2:1 bistability and the initiation of
      arrhythmias.

PMID- 15981860
TI  - A finite volume method for modeling discontinuous electrical activation in
      cardiac tissue.
AB  - This paper describes a finite volume method for modeling electrical activation in
      a sample of cardiac tissue using the bidomain equations. Microstructural features
      to the level of cleavage planes between sheets of myocardial fibers in the tissue
      are explicitly represented. The key features of this implementation compared to
      previous modeling are that it represents physical discontinuities without the
      implicit removal of intracellular volume and it generates linear systems of
      equations that are computationally efficient to construct and solve. Results
      obtained using this method highlight how the understanding of discontinuous
      activation in cardiac tissue can form a basis for better understanding
      defibrillation processes and experimental recordings.

PMID- 15981861
TI  - Polarization of a spherical cell in a nonuniform extracellular electric field.
AB  - Polarization of cells by extracellular fields is relevant to neural stimulation,
      cardiac pacing, cardiac defibrillation, and electroporation. The electric field
      generated by an extracellular electrode may be nonuniform, and highly nonuniform
      fields are produced by microelectrodes and near the edges of larger electrodes.
      We solved analytically for the transmembrane voltage (phi(m)) generated in a
      spherical cell by a nonuniform extracellular field, as would arise from a point
      electrode. Phi(m) reached its steady state value with a time constant much
      shorter than the membrane time constant in both uniform and nonuniform fields.
      The magnitude of phi(m) generated in the hemisphere of the cell toward the
      electrode was larger than in the other hemisphere in the nonuniform field, while
      symmetric polarization occurred in the uniform field. The transmembrane potential
      in oocytes stained with the voltage sensitive dye Di-8-ANEPPS was measured in a
      nonuniform field at three different electrode-to-cell distances. Asymmetric
      biphasic polarization and distance-dependent patterns of membrane voltage were
      observed in the measurements, as predicted from the analytical solution. These
      results highlight the differences in cell polarization in uniform and nonuniform
      electric fields, and these differences may impact excitation and poration by
      extracellular fields.

PMID- 15981862
TI  - Contactless bio-impedance monitoring technique for brain cryosurgery in a 3D head
      model.
AB  - A contactless induced-current bio-impedance system for monitoring brain
      cryosurgery procedure was modeled and numerically simulated, where the excitation
      coil was also performing as the measuring, or pick-up coil. A segmented three
      dimensional (3D) MRI database was used for building the volume conductor
      geometry, and the numerical finite-volume method was employed for solving the
      forward problem for calculating the scalar potential distribution and the second
      order voltage change on the pick-up coil. Several coil configurations were
      considered, varying in their relative positioning to the 3D head model. For each
      case, the sensitivity of the measured voltage change on the excitation coil to
      the volume of a frozen lesion was calculated. The highest sensitivity (1.1 x 10(
      5) relative voltage change per mm3 of frozen tissue) was obtained for a coil
      arrangement where its closest segment to the volume conductor is at the maximum
      distance away from the frozen region position. The simulated system signal-to
      carrier ratio was O(10(-8)).

PMID- 15981863
TI  - Heterogeneous airway versus tissue mechanics and their relation to gas exchange
      function during mechanical ventilation.
AB  - We have advanced a commercially available ventilator (NPB840, Puritan
      Bennett/Tyco Healthcare, Pleasanton, CA) to deliver an Enhanced Ventilation
      Waveform (EVW). This EVW delivers a broadband waveform that contains discrete
      frequencies blended to provide a tidal breath, followed by passive exhalation.
      The EVW allows breath-by-breath estimates of frequency dependence of lung and
      total respiratory resistance (R) and elastance (E) from 0.2 to 8 Hz. We
      hypothesized that the EVW approach could provide continuous ventilation
      simultaneously with an advanced evaluation of mechanical heterogeneities under
      heterogeneous airway and tissue disease conditions. We applied the EVW in five
      sheep before and after a bronchial challenge and an oleic acid (OA) acute lung
      injury model. In all sheep, the EVW maintained gas exchange during and after
      bronchoconstriction, as well as during OA injury. Data revealed a range of
      disease conditions from mild to severe with heterogeneities and airway closures.
      Correlations were found between the arterial partial pressure of oxygen (PaO2)
      and the levels and frequency-dependent features of R and E that are indicative of
      mechanical heterogeneity and tissue disease. Lumped parameter models provided
      additional insight on heterogeneous airway and tissue disease. In summary,
      information obtained from EVW analysis can provide enhanced guidance on the
      efficiency of ventilator settings and on patient status during mechanical
      ventilation.

PMID- 15981864
TI  - Improving hollow fiber dialyzer efficiency with a recirculating dialysate system.
      I: Theory and applicability.
AB  - The mathematical theory that underlies a novel non-regenerated recirculating
      dialysate system (RDS) for improving diffusive clearance in hemodialyzers is
      presented. The theory states the conditions that hemodialyzers must meet to be
      suitable in RDS optimization. We have verified the applicability of the RDS for
      several Cuprophan and polysulfone (PS) commercial dialyzers, showing that PS
      (synthetic) membranes achieve the highest increments of diffusive clearance. A
      numerical simulation analysis over more general conditions defined by the
      dimensionless groups of the system demonstrated that the highest diffusive
      clearance improvements are achieved in dialyzers operating with a low value of
      the diffusive mass-transfer area/blood flow rate ratio. This study has provided
      the base for the assessment of the performance of the RDS as compared to several
      high-efficiency systems, presented in Part II of this work [M. Prado, L. M. Roa,
      A. Palma, and J. A. Milan, Ann. Biomed. Eng. (2004) submitted].

PMID- 15981865
TI  - Smelling renal dysfunction via electronic nose.
AB  - The human body odor plays an important role in social communication in various
      situations, like the olfactory identification of partners and relatives as well
      as in parents-child interactions. In patients with renal dysfunction the compound
      of sweat and volatile gases is changed because of the limited ability for
      removing metabolic products from the blood. The regulation of electrolyte
      composition and acid-base balance are also altered so that the body odor of these
      patients may be significantly influenced by these disorders. We show the ability
      of an electronic nose to detect changes in the human body odor in consequence of
      renal dysfunction by reducing multivariate sensor signals with principal
      component analysis to its first and second principal odor component (POC). All
      healthy subjects could clearly be distinguished from patients with renal failure
      using quadratic discriminant analysis, whereas a correct classification of 95.2%
      (98.4% using 1st-3rd POC) of patients between end stage renal failure and chronic
      renal failure was found. This methodology of analyzing human body odor may also
      provide new approaches for investigating symptoms of renal failure and for
      diagnosing other diseases of internal or cutaneous origin.

PMID- 15981866
TI  - Three-dimensional representation of complex muscle architectures and geometries.
AB  - Almost all computer models of the musculoskeletal system represent muscle
      geometry using a series of line segments. This simplification (i) limits the
      ability of models to accurately represent the paths of muscles with complex
      geometry and (ii) assumes that moment arms are equivalent for all fibers within a
      muscle (or muscle compartment). The goal of this work was to develop and evaluate
      a new method for creating three-dimensional (3D) finite-element models that
      represent complex muscle geometry and the variation in moment arms across fibers
      within a muscle. We created 3D models of the psoas, iliacus, gluteus maximus, and
      gluteus medius muscles from magnetic resonance (MR) images. Peak fiber moment
      arms varied substantially among fibers within each muscle (e.g., for the psoas
      the peak fiber hip flexion moment arms varied from 2 to 3 cm, and for the gluteus
      maximus the peak fiber hip extension moment arms varied from 1 to 7 cm). Moment
      arms from the literature were generally within the range of fiber moment arms
      predicted by the 3D models. The models accurately predicted changes in muscle
      surface geometry over a 55 degrees range of hip flexion, as compared to changes
      in shape predicted from MR images (average errors between the model and measured
      surfaces were between 1.7 and 5.2 mm). This new framework for representing muscle
      will enhance the accuracy of computer models of the musculoskeletal system.

PMID- 15981867
TI  - Human movement reconstruction from video shot by a single stationary camera.
AB  - One of the key techniques in the research of human motion analysis is the
      reconstruction of human spatial motion, which utilizes the anatomic points
      positions that can uniquely define the position and orientation of all anatomical
      segments. In this paper, upon the basis of Direct Linear Transform (DLT) and a
      human biomechanical model, the method to reconstruct human motion from an image
      sequence shot by a single stationary camera was described. In this method, the
      Lagrange Multiplier Method was used to minimize the difference between the actual
      and reconstructed length of limbs. This approach here is more comprehensive than
      previous methods that utilized cost functions to select results from feasible
      solutions. To examine this method, a practical human motion measured by a motion
      analysis system was selected and reconstructed. The spatial positions of joints
      were predicted with an average R2 of 0.9722 and mean residual error of 0.0022 m.
      This approach presented here provides a simple way to reconstruct the human
      spatial motion only utilizing a single camera.

PMID- 15981868
TI  - Effects of EGF and bFGF on irradiated parotid glands.
AB  - Radiotherapy is common treatment for head-and-neck cancer, during which the
      salivary glands are often included within the radiation field. The most common
      side effect of this treatment is the development of oral dryness (xerostomia).
      This study considers the administration of epidermal growth factor (EGF) and
      basic fibroblast growth factor (bFGF or FGF2) at physiological concentrations
      before and after irradiation in order to repair radiation-induced damage in
      salivary gland cells. As a preliminary examination of the efficacy of this
      approach we have characterized the effects of EGF and bFGF on the apoptotic
      response of 15-Gy irradiated rat salivary glands in vitro. Also, we have
      developed a controlled-release delivery system to effectively administer the
      growth factor to the gland since local delivery is essential to avoid unwanted
      protection of cancer cells. In vitro administration of bFGF prior to and
      immediately after irradiation partially protected (44%) the rat parotid gland.
      EGF did not show any significant radioprotective effect on parotid glands after a
      single 15-Gy irradiation dose. Encapsulation, storage and release of bFGF from
      biodegradable 50/50 PLGA microspheres did not affect the functionality of the
      growth factor in vitro.

PMID- 15981869
TI  - Coordinated movement of bile canalicular networks reconstructed by rat small
      hepatocytes.
AB  - Hepatocytes in vivo have a potential for liver regeneration, but it has been very
      difficult to reconstruct hepatic organoids in vitro. Recent studies have shown
      that small hepatocytes (SHs) can reconstruct hepatic organoids including
      functional bile canaliculi (BC). In the present study we analyzed the movement of
      BC formed in the hepatic organoids, focusing on the coordination of contraction
      and dilation among cells and the mechanism producing the coordination. Hepatic
      cells, including SHs, were isolated from an adult rat liver and cultured. Time
      lapse images of BC movements were taken and analyzed in cells treated with or
      without cytochalasin B (CB). Time-lapse images revealed that all BC, regardless
      of region contracted in a coordinated manner. Actin filaments were observed along
      the BC even after the BC networks treated with CB dilated markedly.
      Microinjection of dye was also carried out to investigate the flow thorough BC.
      Secreted fluorescein from the injected cell flowed along BC, and gap junctional
      protein connexin 32 was expressed along BC networks, suggesting cell-to-cell
      communication. Thus, groups of hepatocytes in the hepatic organoids act in a
      coordinated manner through intercellular communication.

PMID- 15981870
TI  - An inverse approach to determine solute and solvent permeability parameters in
      artificial tissues.
AB  - This study presents a generic numerical model to simulate the coupled solute and
      solvent transport in tissue sections during addition and removal of chemical
      additives or cryoprotective agents (CPA; dimethylsulfoxide or DMSO). Osmotic
      responses of various tissue cells within the artificial tissue are predicted by
      the numerical model with three model parameters: Permeability of the tissue cell
      membrane to water (Lp), permeability of the tissue cell membrane to the solute or
      CPA (omega), and the diffusion coefficient of the solute or CPA in the
      extracellular space (D). By fitting the model results with published experimental
      data on solute/water concentrations at various locations within an artificial
      tissue, we were able to determine the permeability parameters of artificial
      tissue cells in the presence of 1.538 M DMSO. Lp and omega were determined at
      three different locations within the artificial tissue assuming a constant value
      of solute diffusivity (D = 1.0 x 10(-9) m2/s). The best fit values of Lp ranged
      from 0.59 x 10(-14) to 4.22 x 10(-14) m3/N-s while omega ranged from 0 to 6.6 x
      10(-13) mol/N-s. Based on these values of Lp and omega, the solute reflection
      coefficient, sigma = 1 - omegav(-)CPA/Lp, ranged from 0.9923 to 1.0. The relative
      values of omega and sigma suggest that the artificial tissue cells are relatively
      impermeable to DMSO (or omega approximately 0 and sigma approximately 1.0). This
      observation was used to modify our model to predict the values of Lp and D
      assuming omega = 0 and sigma = 1.0. The best fit values of Lp ranged from 640 x
      10(-14) to 2.1 x 10(-14) m3/N-s while D ranged from 0.63 x 10(-9) to 1.52 x 10(
      9) m2/s. The permeability parameters obtained in the present study represent the
      first such effort for artificial tissues.

PMID- 15981871
TI  - [Effects of different manure on lily quality].
AB  - OBJECTIVE: To determine the best manure scheme of lily (Lilium lancifolium).
      METHODS: Determining lilypolysaccharide and phosphatide contents through phenol
      hydrate-sulfuric acid and molybdenum blue colorimetric method. RESULTS: The
      content of efficacious composition in applying fertilizer on the leaves is higher
      than average and possium fertilizer can increase lilypolysaccharide content.
      CONCLUSION: Possium fertilizer is important in early stage and leaf fertilizer
      can improve lily quality.

PMID- 15981872
TI  - [Study on antioxidant activity of essential oils and its monomer from Pelargonium
      graveolens].
AB  - The antioxidant effects of essential oil and monomer as well as residue and waste
      water after distillation from buds, stems and leaves of Pelargonium graveolens
      were studied by the method of 1,1-diphenyl-2-picryl hydrazyl free redical
      (DPPH*). It showed that each sample in the test had the antioxidant effect. The
      extraction of the leaf collected in noon had the strongest antioxidant effect,
      the residue and waste water had also strong antioxidant effect. It shows that
      some antioxidant chemical abounds in the residue of natural essential industry,
      and it also shows feasibility of integrated use of Pelargonium graveolens.

PMID- 15981873
TI  - [Analysis of Chinese drug beimu and its fake species with clustering analysis and
      FTIR spectra].
AB  - OBJECTIVE: To identify Chinese drug Beimu from its fake species. METHOD: IR
      spectra was obtained by Fourier Transform Infrared Spectroscopy (FTIR) and
      clustering analysis was adopted for authentication. RESULT: There were
      significant differences between Beimu and its fake species. CONCLUSION: The
      established method was quick, sensitive and accurate. It could be used for the
      differentiation of different species of Beimu materials and their fake species.

PMID- 15981874
TI  - [Identification on Herba Hedyotidis by HPLC fingerprint pattern method].
AB  - OBJECTIVE: To establish a new identification and analysis method of Herba
      Hedyotidis. METHOD: HPLC fingerprint pattern method. RESULT: Experiment and
      analysis were carried out on seven samples, the standard HPLC fingerprint pattern
      method and characterisitic diffraction peaks of Herba Hedyotidis were obtained.
      CONCLUSION: This method can be used for the identification of Herba Hedyotidis.

PMID- 15981875
TI  - [Studies on chemical constituents from Elsholtzia bodinieri Vaniot].
AB  - OBJECTIVE: To study the chemical constituents from Elsholtza bodinieri Vaniot.
      METHOD: The chemical constituents were isolated and repeatedly purified on silica
      gel column and the structures were elucidated by the NMR spectra and physico
      chemical properties. RESULTS: Seven compounds were obtained and they are
      identified as 5,7-dihydroxyflavone, 5,7,3',4-tetrahydroxyflavone, 5,3',4'
      trihydroxy-7-O-beta-D-glucoside, acacetin, oleanolic acid, beta-sitosterol,
      daucosterol. CONCLUSION: All the compounds were obtained from Elsholtzia
      bodinieri Vaniot for the first time.

PMID- 15981876
TI  - [Studies on the chemical constituents from Rhodiola dumulosa (I)].
AB  - The rhizoma samples of Rhodiola dumulosa were cut into fragments and extracted by
      95% EtOH. This extract was successively extracted with Et2O, EtOAc, n-BuOH. Six
      compounds were obtained from the Et2O fraction. The structures of six compounds
      were identified. The compounds are beta-sitosterol (I), herbacetin-8-methyl ether
      (II), kaemperol (III), kaemperol-7-O-alpha-L-rhamnoside (IV), beta-sitosterol
      glucoside (V), herbacetin-7-alpha-L-rhamnoside (VI). beta-sitosterol, herbacetin
      8-methyl ether and kaemperol of compounds were obtained from this plant for the
      first time.

PMID- 15981877
TI  - [Studies on the chemical constituents from Fructus Rubi].
AB  - Five compounds have been isolated from Fructus Rubi. On the basis of spectral
      analysis and physicochemical properties, their structures were establised as 4
      hydroxy-3-methoxybenzoic acid (I), p-hydroxybenzoic acid (II), gallic acid (III),
      tiliroside (IV) and ellagic acid (V). I, II and III were found from the plant for
      the first time.

PMID- 15981878
TI  - [Studies on chemical constituents from Salvia roborowskii Maxim].
AB  - OBJECTIVE: To study the chemical constituents from Salvia roborowskii Maxim.
      METHODS: Chromatography and spectroscopic analysis were employed to isolate and
      elucidate the chemical constituents in the plant. RESULTS: Three compounds were
      isolated and elucidated as 1 beta-hydroxy-lupeol (I), quercetin-3-O-beta-D
      glucoside (II), rutin (III). CONCLUSION: I - III were isolated from this plant
      for the first time.

PMID- 15981879
TI  - [Studies on constituents from Ligularia narynensis].
AB  - OBJECTIVE: To study the chemical constituents from Ligularia narynensis. METHOD:
      The constituents were isolated and purified by column chromatography and the
      structures were identified by physicochemical properties and spectral analysis.
      RESULT: Six compounds were obtained as aurantiamide benzoate (1), aurantiamide
      acetate (2), 1-O-octacosanoylgerol (3), beta-sitosterol (4), daucesterol (5),
      ferulic acid (6). CONCLUSION: All these compounds were obtained from this plant
      for the first time. Compounds 1 and 2 were isolated for the first time from this
      genus.

PMID- 15981880
TI  - [Study on the chemical constituents from Rumex japonicus Houtt].
AB  - OBJECTIVE: To study the chemical constituents in dried roots of Rumex japonicus
      Houtt. METHODS: Isolation and purification of chemical constituents from Runmex
      japonicus Houtt. were conducted by solvent extraction and chromatography. Their
      structures were identified by spectrum analysis. RESULTS: Two compounds were
      isolated from the acrtone extract of the roots and identified as emodin and
      rutin. CONCLUSION: Compound II is obtained from this plant for the first time.
      The task provided evidence for the exploitation and utilization of this plant
      resources.

PMID- 15981881
TI  - [Quantitative determination of anethole in the fruit of Illicium verum from
      various places of Guangxi province].
AB  - The quantitative determination of anethole in the fruit of Illicium verum from
      various places of Guangxi province were determined by GC. The average recovery
      rate and the RSD are 102.31%, 1.78% respectively. The content of anethole in the
      fruit of Illicium verum in various places were all more than 4.5%.

PMID- 15981882
TI  - [Chlorogenic acid content comparison of different processed products of Ilex
      hainanensis Merr].
AB  - OBJECTIVE: To control different processed products of Ilex hainanensis Merr
      quality. METHODS: Using HPLC to determine chlorogenic acid of Ilex hainanensis
      Merr. Measure wavelength is 327 nm. RESULTS: The linear range of chlorogenic acid
      was good from 0.84 microg to 5.04 microg (r = 0.9996). The average recovery was
      100.46% (RSD = 1.33%). CONCLUSION: This method is convenient, fast, accurate, can
      be applied to quality control of the different processed products of Ilex
      hainanensis Merr.

PMID- 15981883
TI  - [The study on skin wound healing promoting action of sodium usnic acid].
AB  - OBJECTIVE: To study the effects of sodium usnic acid on proliferation of
      fibroblasts and skin wound healing. METHODS: L929 fibroblasts were incubated in
      culture medium containing sodium usnic acid, the proliferation of fibroblasts
      were measured by MTT. Skin wound healing promoting action of sodium usnic acid
      was determined in rats. RESULTS: Sodium usnic acid does not showed proliferation
      promoting activity for L929 fibroblasts, sodium usnic acid by external
      application accelerated healing of rat backskin wound. The wound-healing rate of
      sodium usnic acid was higher than that of the control group at the 2th - 12th day
      after treatment. CONCLUSION: Sodium usnic acid can accelerate skin wound healing,
      the effects was not by stimulating proliferation of fibroblasts.

PMID- 15981884
TI  - [An experimental study on proliferative effects and apoptotic effects of
      podophyllic acid in K562 cells].
AB  - OBJECTIVE: To study the effects of podophyllic acid on proliferation and
      apoptosis in human leukemia K562 cells. METHODS: The inhibitory effects of
      podophyllic acid on K562 cells were investigated by clony-formation and MTT
      colorimetric assay. The apoptotic effects were observed by FCM. RESULTS:
      Podophylic acid could inhibit the proliferation of K562 cells and there were a
      significant difference between experimental and control groups (P < 0.01). There
      was a marked positive correlation between drug concentration and the inhibitory
      rates. Podophyllic acid could induce apoptosis of K562 cells. When K562 cells
      were treated with 5.0 microg/ml podophyllic acid for 48 hours, apoptosis occurred
      to the largest extent. The apoptosis rate of podophyllic acid was 33.5%.
      CONCLUSIONS: Podophyllic acid has antitumor effect, but the change of structure
      affects the function of derivatives of podophylloxin greatly.

PMID- 15981885
TI  - [Studies of Calotes versicolor on the sexual function amelioration mechanism by
      hypothalamus inhibition in immature male rats].
AB  - OBJECTIVE: To study the amelioration mechanism of Calotes versicolor petroleum
      ether extracts (CVPEE) on hypothalamus inhibition sexual function induced by
      morphine in immature male rats. METHODS: The hypothalamus inhibition induced by
      morphine in immature male rats was used as model of the testis reproductive
      functional disturbance. The rats was given CVPEE for 21 days. The levels of
      testosterone (T) and follicle stimulating hormone (FSH) in serum were determined
      by the radio-immunoassay. The nitrogen monoxide (NO) contents in serum and penis
      tissue were determined by nitrate reductase method. The sexual organ and
      auxiliary sexual organ coefficient were calculated and the histopathological
      changes in the testes and epididymides were observed with microscope. RESULTS:
      CVPEE groups (low and high dosage groups) significantly enhanced the level of
      serum T, compared with model group (P < 0.05); the low dosage group decreased
      obviously the level of FSH. CVPEE had the tendency to increase NO contents in
      serum and penile tissue. The microscopic examination results showed that the
      testis tissue in CVPEE group was damaged more gently than those in model group.
      CONCLUSION: CVPEE can enhance the level of serum T and NO contents in penile
      tissue, improve the sexual functional disturbance in hypothalamus inhibition
      induced by morphine in immature male rats. It indicated that CVPEE had the
      effects by the hypothalamus-hypophysis-gonad axial function.

PMID- 15981886
TI  - [Effect of ginsenoside Rg1 on neprilysin expression induced by LPS in SK-N-SH
      cell line].
AB  - OBJECTIVE: To investigate the effect of ginsenoside Rg1 on the neprilysin (NeP)
      expression induced by LPS in SK-N-SH cell line. METHODS: MTT was used to measure
      the survival rate of SK-N-SH cultured with ginsenoside Rg1 at different
      concentrations (5, 10, 20 micromol/L) and LPS (50 mg/L). The expression of NEP
      was measured by RT-PCR. RESULT: The survival rate of SK-N-SH was obviously
      inhibited by LPS, the expression of NEP was decreased. On the other hand, the
      above alteration induced by LPS was reversed by ginsenoside Rg1. CONCLUSION: This
      study demonstrates that LPS can cause cell damage and the decrease of NEP
      expression. Ginsenoside Rg1 can protect SK-N-SH cells against the injury induced
      by LPS, increase NEP expression.

PMID- 15981887
TI  - [Protective effects of Panax notoginseng saponins against pathological lesion of
      cholinergic neuron in rat model with Alzheimer' s disease].
AB  - OBJECTIVE: To observe the protective effect of Panax notoginseng saponins (PNS)
      against pathological lesion of cholinergic neuron in rat model with Alzheimer' s
      disease (AD). METHODS: The AD rat model was established by intra-peritoneal
      injection of D-galactose combined with excitatory neurotoxin ibotenic acid (IBA)
      injection into bilateral nbM. The activity and content of choline
      acetyltransferase (ChAT), the cell morphology and number of cholinergic neuron in
      brain were determined by immunohistochemistry analysis. RESULTS: PNS could reduce
      the pathological lesion of cholinergic neuron, including the level of ChAT and
      number of cholinergic neuron, as compared with those of model group's rats.
      CONCLUSION: PNS plays a protective role in pathological lesion of cholinergic
      neuron in AD rat model.

PMID- 15981888
TI  - [Effect of phillyrin on the anti-obesity in nutritive obesity mice].
AB  - OBJECTIVE: To study on the anti-obesity effect of phillyrin in nutritive obesity
      mice. METHOD: The alimentary obesity model was established by hyperalimentation.
      The wet weight of fat, fat index, number of fat cells per unit visual field,
      Lee's index, jejunum microvillus area, serum triglyceride and cholesterol were
      selected to observe the anti-obesity effect of phillyrin. RESULT: Phillyrin could
      lower wet weight of fat (P < 0.01), fat index (P < 0.05 or P < 0.01), diameter of
      fat cell and Lee's index (P < 0.05), decrease the jejunum microvillus area, lower
      the level of serum triglyceride and cholesterol. CONCLUSION: Phillyrin has anti
      obesity effect in nutritive obesity mice.

PMID- 15981889
TI  - [The effect of bamboo leaves extract on hemorheology of normal rats].
AB  - Sixty rats were randomly divides into six groups. Blood stasis model was set up
      by sc isoprenaline, and different dose of BLE (15 mg/kg, 30 mg/kg and 60 mg/kg)
      were iv. The effects of BLE on rat's blood viscosity, plasma viscosity, FIB, ESR,
      TK, electrophoresis times and HCT were measured by automatic analysis system.
      Sixty mice were randomly divided into six groups, and the serum cholesterol of
      the high cholesterol's mice was obtained by eyepit vein and measured. The results
      showed that BLE (15 mg/kg, 30 mg/kg and 60 mg/kg) could reduce blood viscosity,
      plasma viscosity, FIB, ESR, TK, HCT and increase the speed of electrophoresis
      time in blood adhesion model, and BLE (22.5 mg/kg, 45 mg/kg, 90 mg/kg) could
      significantly reduce serum cholesterol of the high cholesterol's mice.

PMID- 15981890
TI  - [The study on prescription and preparation of the sustained-released capsule of
      gegen isoflavones].
AB  - OBJECTIVE: To study the preparation of the sustained-released capsule of Gegen
      isoflavones (SRCGI) and choose the best prescription. METHODS: EC and HPMC were
      used as sustained-released excipients. Uniform layout test was employed to design
      the formulation. RESULTS: The best prescription release drug Q0.5h = 50% - 53%,
      to 100% at 12h and its dissolution behavior belongs to Higuchi Kinetics, Q =
      17.19t1/2 +/- 38.75, r = 0.9959. CONCLUSION: SRCGI obtained desirable effect of
      drug release.

PMID- 15981891
TI  - [Effects of packaging on the stability of vitamin E in peach kernels stored at
      high temperature].
AB  - Peach kernels with three different kinds of packaging, including routine, vacuum
      and edible film, were put into an accelerated test in order to study the effects
      of packaging on the stability of vitamin E, gamma-, alpha-, and delta-tocopherol.
      The result indicated that among the three kinds of packaging, the stability of
      vitamin E in the samples with vacuum packaging was the best, and with routine
      packaging was the worst. And for the samples with the same kind of packaging, the
      stabilities of gamma-, alpha- and delta-tocophero decreased one by one.

PMID- 15981892
TI  - [Study on ultrasonic extraction technics of oleanolic acid in Akebia trifoliata].
AB  - OBJECTIVE: To optimize the ultrasonic extraction condition for oleanolic acid
      from Akebia trifoliata. METHOD: According to the orthogonal design L9 (3(4)), the
      optimum ultrasonic extraction technique was sought through experimental
      investigation, and was compared with the routine extraction technics. The
      contents of oleanclic acid were determined by UV-spectrophotometry. RESULT: The
      order of factors to affect the oleanolic acid extraction was extraction time >
      ethanol concentration > ultrasonic power > ration of interval time to ultrasonic
      time. The optimum ultrasonic extractions were A2B3C1D2. CONCLUSION: Compared with
      traditional extraction, ultrasonic method can save time, be easy to operate,
      improve extraction rates and need no heating.

PMID- 15981893
TI  - Essential hypotension is accompanied by deficits in attention and working memory.
AB  - In the present study, the authors investigated the relationship between low blood
      pressure (BP) and attentional performance through the application of a
      multidimensional diagnostic approach. The authors compared 40 subjects with
      essential hypotension (mean systolic BP = 97.6 mmHg) with 40 normotensive
      controls (mean systolic BP = 124.1 mmHg) using 6 computer-based tasks measuring
      tonic and phasic alertness; selective, divided, and sustained attention; and
      working memory. To control for possible confounders, the authors used a test
      battery examining motor performance and a mood questionnaire. BP was monitored
      continuously during the entire experiment. Hypotensives showed prolonged
      execution times in each of the attentional tasks (p < .001). Moderately decreased
      accuracy was found in the tests assessing sustained attention (p = .059) and
      working memory (p = .012). Moreover hypotensives showed smaller elevations in BP
      during the execution of the cognitive tasks. This study is the first to
      demonstrate the relationship between BP and cognitive performance while
      controlling for motor function and mood.

PMID- 15981894
TI  - Weight loss and biomedical health improvement on a very low calorie diet: the
      moderating role of history of weight cycling.
AB  - In this study, the authors examined biomedical consequences of participation in a
      professionally delivered, multifaceted very low calorie diet (VLCD) program and
      whether the degree of benefit associated with treatment was moderated by history
      of weight cycling. The authors monitored body weight and biomedical health
      indicators in 66 severely obese outpatients on a VLCD liquid fast. Participants
      remained on the VLCD for a median of 55 (range 9 to 247) days. Treatment was
      associated with significant pre-to-post improvements on body weight, systolic and
      diastolic blood pressure, triglycerides, and cholesterol. History of weight
      cycling (independent of age) was inversely related to the magnitude of absolute
      pre-to-post treatment changes in systolic and diastolic blood pressure, as well
      as to the rate of weight change. More intensive, longer term, and explicit
      maintenance components, especially aimed at individuals with multiple weight loss
      regain episodes, may be necessary to facilitate weight loss and attain optimal
      health benefits from VLCDs.

PMID- 15981896
TI  - [Cardiac pharmacology reveals multiple sources of error: old heart,
      pharmacologically abused].

PMID- 15981895
TI  - Psychosocial stress and cardiovascular disease. Part 3: Clinical and policy
      implications of research on the transcendental meditation program.
AB  - Cardiovascular disease (CVD) remains the leading cause of death in the United
      States today and a major contributor to total health care costs. Psychosocial
      stress has been implicated in CVD, and psychosocial approaches to primary and
      secondary prevention are gaining research support. This third article in the
      series on psychosocial stress and CVD continues the evaluation of one such
      approach, the Maharishi Transcendental Meditation program, a psychophysiological
      approach from the Vedic tradition that is systematically taught by qualified
      teachers throughout the world. Evidence suggests not only that this program can
      provide benefits in prevention but also that it may reduce CVD-related and other
      health care expenses. On the basis of data from the studies available to date,
      the Transcendental Meditation program may be responsible for reductions of 80% or
      greater in medical insurance claims and payments to physicians. This article
      evaluates the implications of research on the Transcendental Meditation program
      for health care policy and for large-scale clinical implementation of the
      program. The Transcendental Meditation program can be used by individuals of any
      ethnic or cultural background, and compliance with the practice regimen is
      generally high. The main steps necessary for wider adoption appear to be: (1)
      educating health care providers and patients about the nature and expected
      benefits of the program, and (2) adjustments in public policies at the state and
      national levels to allow this program to be included in private and public health
      insurance plans.

PMID- 15981897
TI  - [Cardio-geriatric polypragmatism. Pharmacotherapy in the elderly: "individual
      experiments"].

PMID- 15981898
TI  - [Phototherapy of nasal mucosa: is ultraviolet light modify allergic rhinitis
      (interview by Dr. Judith Neumaier)].

PMID- 15981899
TI  - [No anger when the man snores. He only wants to protect his wife!].

PMID- 15981900
TI  - [Urinary incontinence: new medications and minimally invasive surgical
      techniques. Improved diagnosis, more effective treatment].

PMID- 15981901
TI  - [Female urinary incontinence].
AB  - Several million women suffer from urinary incontinence in Germany. Stress and
      urge incontinence are especially clinically relevant. Training of the pelvic
      floor muscles (vaginal cones, electrical stimulation, biofeedback, and so forth)
      plays a central role in the conservative therapy of stress incontinence. The use
      of devices such as incontinence tampons and urethral pessaries is also common. A
      medication for the therapy of stress incontinence, which improves the closure of
      the urethral sphincter, has been on the market since 2004. In the operative
      area,the insertion of a tension-free vaginal tape (TVT) has gained acceptance in
      recent years. Anticholinergics are the primary medication used in the treatment
      of urge incontinence. Local estrogens, low frequency electrical stimulation,
      phytotherapeutics and the like have supportive effects.

PMID- 15981902
TI  - [Management of urinary incontinence in the aging man].
AB  - The increasing prevalence and incidence of male urinary incontinence in senium
      necessitate a specific as well as symptom and etiologically-oriented therapy. In
      addition to the conservative care with absorbent products, catheterization
      methods are available. Moreover, the problem can be successfully controlled in
      the majority of the patients through very specific drug and surgical therapeutic
      concepts.

PMID- 15981903
TI  - [Blood pressure limits for the initiation and goal of antihypertensive therapy.
      Blood pressure and cardiovascular risk].

PMID- 15981904
TI  - [Mild cognitive impairment: A review of the literature].
AB  - People with MCI suffer from a moderate memory impairment, from deficits in
      attention and cognitive flexibility but do not fulfil the diagnostic criteria of
      dementia. These patients feel forgetful, and sometimes may have problems with
      their jobs and families because of their forgetfulness. In many cases (10-15% per
      year), MCI is leading to Alzheimer's disease. The sooner MCI is diagnosed and
      treated, the better the transition into Alzheimer's disease may perhaps be
      delayed. The diagnostic instruments are the same as for the diagnosis of
      Alzheimer's disease: biomarkers of the cerebrospinal fluid, neuroimaging and
      neuropsychological testing. Neuropsychological testing already shows deficits,
      even when neuroimaging findings still seem to be normal. Therapy of MCI is
      basically like the treatment of Alzheimer's disease: symptomatic treatment with
      cholinesterase-inhibitors or antioxidants, and compensatory psychological
      approaches.

PMID- 15981905
TI  - [Although national health insurance covers general practice outlay, contract
      physicians are responsible for carelessness in clinics].

PMID- 15981906
TI  - [Initial evaluation of disease management. DMP patients are better off].

PMID- 15981907
TI  - [Action of KBV. Join the campaign against bureaucracy!].

PMID- 15981908
TI  - [Lowering LDL cholesterol frequently does not adhere to guidelines. Also regard
      intestinal cholesterol source].

PMID- 15981909
TI  - [For my coronary heart disease patients I strive for a 70 mg/dl LDL level
      (interview by Dr. med. Dirk Einecke)].

PMID- 15981910
TI  - [Effective and 15 years experience. New add-on option in epilepsy therapy]].

PMID- 15981911
TI  - [Control of side effects. Add on therapy demonstrates good tolerance].

PMID- 15981912
TI  - [Acute monarthritis. A really hot knee].

PMID- 15981913
TI  - [The devil exorcised by Beelzebub].

PMID- 15981914
TI  - Evidence-based medicine grows up.
AB  - By strategically addressing the challenges and user requirements of EBM,
      healthcare organizations can implement EBM systems that leverage their existing
      clinical investments and garner fast clinician adoption.

PMID- 15981915
TI  - Physician practice management. What works. A one-two punch.
AB  - Growing multispecialty practice implements a new practice management/EMR system,
      reducing costs and diverting resources to new revenue-generating activities.

PMID- 15981916
TI  - Financial information systems Good problem$.
AB  - An Ohio hospital uses financial software to solve patient satisfaction problems-
      and as an added benefit, slices its A/R days by a third.

PMID- 15981917
TI  - Health plans & technology--case history. The best prescription for savings and
      satisfaction.
AB  - Transparent out-of-pocket drug costs allow consumers to make cost-effective
      prescription choices for themselves and health plans.

PMID- 15981918
TI  - Wireless-case history. Monitoring med mobile.
AB  - A pediatric trauma center leverages its wireless infrastructure to help improve
      patient outcomes with innovations including a point-of-care medication
      administration system.

PMID- 15981919
TI  - Molecular pharmaceutics, a vision for the future.

PMID- 15981920
TI  - HPMA copolymer-bound doxorubicin induces apoptosis in human ovarian carcinoma
      cells by a Fas-independent pathway.
AB  - The mechanism of cell death in A2780 human ovarian carcinoma cells induced by
      free doxorubicin (DOX) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer
      bound DOX [P-(GFLG)-DOX] was investigated. In particular, the involvement of the
      Fas receptor system in drug-induced apoptosis was evaluated. P-(GFLG)-DOX was
      shown to effect apoptosis-induced tumor cell death as manifested by positive
      Annexin V-FITC staining, cleavage of procaspase 3 and its physiological
      substrate, poly(ADP-ribose) polymerase (PARP), and cleavage of procaspase 8.
      Using the fluorochrome-labeled caspase inhibitor assay, it was found that both
      free DOX and P-(GFLG)-DOX activated caspases 3 and 9, but both forms of DOX did
      not have an effect on the activity of caspase 8, when compared to untreated
      cells. It was shown that free DOX and P-(GFLG)-DOX upregulated Fas receptor
      expression at the cell membrane in a time-dependent manner. Triggering the drug
      induced Fas receptor with an exogeneous soluble Fas ligand (sFasL) resulted in an
      increase in the extent of apoptotic cell death, indicating that the Fas signaling
      pathway remained functionally active. Also, antagonistic anti-Fas ZB4 antibody
      blocked the increase in the level of apoptosis following the application of
      sFasL, but did not interfere with drug-induced apoptosis. The study of the
      functional activity of the Fas receptor and of the activation of the most
      proximal effector of the caspase cascade, caspase 8, indicated that the Fas
      receptor pathway was not decisive in the induction of cell death by free DOX and
      P-(GFLG)-DOX in A2780 cells. This study suggests further investigation of the
      involvement of the mitochondrial pathway in A2780 cell apoptotic death, induced
      by free and HPMA copolymer-bound DOX.

PMID- 15981921
TI  - Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates.
AB  - Antitumor activity of linear, beta-cyclodextrin polymer (CDP)-camptothecin (CPT)
      conjugates (HGGG6, LGGG10, HG6, and HGGG10) is investigated in nude mice bearing
      human LS174T colon carcinoma tumors. These conjugates differ in polymer molecular
      mass [97 kDa (H) or 35 kDa (L)], CDP-CPT linker structure [glycine (G) or
      triglycine (GGG)], and CPT loading [ca. 6 wt % (6) or 10 wt % (10)]. Maximum
      tolerable doses (MTDs) of the three conjugates, LGGG10, HG6, and HGGG10, are
      determined to be 36, 9, and 9 mg of CPT/kg, respectively, while the MTD of the
      CDP alone exceeds 240 mg/kg (highest value investigated). The three CDP-CPT
      conjugates with high polymer molecular masses (HGGG6, HG6, and HGGG10)
      demonstrate antitumor activity at their MTDs superior to that of CPT at the same
      amount and to that of irinotecan at its optimal dose. They also show tumor growth
      inhibition that is superior to that of the conjugate containing the low-molecular
      mass polymer (LGGG10) at the same dose of CPT. No significant effects of CPT
      weight loading or linker structure on tumor growth delay are observed. However,
      conjugates containing G appear to be less toxic than these with GGG. These
      antitumor studies demonstrate that the CDP-based conjugates of CPT exhibit tumor
      growth inhibition superior to that of CPT or irinotecan at the conditions
      employed in this study. The striking observation is that a short course of
      treatment with the polymer conjugates gives long-term control of tumor growth
      that does not occur with either CPT or irinotecan. Intracellular CDPs are
      demonstrated by analyzing cells that were cultured in the presence of rhodamine
      labeled CDP (HRhod) containing medium using both confocal microscopy and flow
      cytometry. The long-term therapeutic efficacy of CDP-CPT conjugates observed in
      mice may in part be due to the sustained release of CPT from these conjugates in
      the acidic, intracellular compartments since these conjugates are shown to have
      significantly slower release rates at acidic pH than at physiological pH.

PMID- 15981922
TI  - Nucleobase- and p-glycoprotein-mediated transport of AG337 in a Caco-2 cell
      culture model.
AB  - This study aimed to determine the intestinal transport characteristics of AG337.
      Caco-2 cell monolayers were used for directional transport of AG337. The results
      indicated that the rate of basolateral (BL) to apical (AP) or secretory transport
      of AG337 was always higher than the rate of AP to BL or absorptive transport. The
      BL-AP/AP-BL ratio increased from 7.6 to 17.2 as the concentration increased from
      10 to 75 microM and stabilized afterward. The following results suggest that the
      p-glycoprotein is involved in the AP efflux of AG337. (1) Verapamil completely
      abolished the directional transport. (2) The apparent activation energy for
      secretory transport was high (33 kcal/mol). (3) Secretory transport was inhibited
      by verapamil (63%) and dipyridamole (35%), but not by probenecid. (4) AP to BL
      transport was enhanced by verapamil (232%) and dipyridamole (41%), but was not
      altered by probenecid or an AP pH change. An additional carrier mechanism may be
      involved in the AP uptake of AG337 because (1) absorptive permeabilities
      decreased as the concentration increased even though secretory permeabilities
      remained the same, (2) the absorptive transport rate was 37% lower in a medium
      containing verapamil and dipyridamole than in a medium containing only verapamil,
      and (3) the absorptive transport rate was also lower in a medium containing
      verapamil and a nucleobase mixture (consisting of adenine, hypoxanthine, and
      xanthine at 100 microM each) than in a medium containing verapamil only. Apical
      transport of AG337 in the Caco-2 cells is mediated, at least in part, by p
      glycoprotein (efflux) and a nucleobase transporter that transports (uptake)
      nucleic bases.

PMID- 15981923
TI  - Comparison of human and monkey peptide transporters: PEPT1 and PEPT2.
AB  - Human proton-dependent peptide transporters, PEPT1 and PEPT2, mediate the
      cellular uptake of di- and tripeptides as well as a variety of drug molecules.
      Although PEPT1 and PEPT2 have been cloned from many species, there are no data
      available for monkey, an important pharmacological and preclinical species in
      drug development. In this study, it was first verified that monkey intestine
      transports a model dipeptide, Gly-Sar, in a proton-dependent manner (0.30 +/-
      0.05 pmol cm(-2) s(-1) at pH 6.0 and 0.10 +/- 0.03 pmol cm(-2) s(-1) at pH 7.4)
      in the absorptive direction, presumably by monkey PEPT1. RT-PCR and rapid
      amplification of cDNA ends (RACE) were then used to clone monkey PEPT1 and PEPT2.
      Monkey PEPT1 (2127 bp and 708 amino acids) was found to be >94 and > 92%
      identical to human PEPT1 at the cDNA and amino acid level, respectively. Monkey
      PEPT2 (2190 bp and 729 amino acids) was found to be > 97% identical to human
      PEPT2 at both the cDNA and amino acid levels. Functional comparison of human and
      monkey peptide transporters expressed in HeLa cells suggested that
      functionalities of PEPT1 and PEPT2 were largely conserved in terms of Gly-Sar
      uptake kinetics and inhibitor specificity (for most tested substrates). Finally,
      Northern and RT-PCR analyses revealed some differences in tissue mRNA levels of
      peptide transporters between human and monkey.

PMID- 15981924
TI  - Nanoparticle-mediated wild-type p53 gene delivery results in sustained
      antiproliferative activity in breast cancer cells.
AB  - Gene expression with nonviral vectors is usually transient and lasts for only a
      few days. Therefore, repeated injection of the expression vector is required to
      maintain a therapeutic protein concentration in the target tissue. Biodegradable
      nanoparticles (approximately 200 nm diameter) formulated using a biocompatible
      polymer, poly(D,L-lactide-co-glycolide) (PLGA), have the potential for sustained
      gene delivery. Our hypothesis is that nanoparticle-mediated gene delivery would
      result in sustained gene expression, and hence better efficacy with a therapeutic
      gene. In this study, we have determined the antiproliferative activity of wild
      type (wt) p53 gene-loaded nanoparticles in a breast cancer cell line.
      Nanoparticles containing plasmid DNA were formulated using a multiple-emulsion
      solvent evaporation technique. To understand the mechanism of sustained gene
      expression with nanoparticles, we monitored the intracellular trafficking of both
      the nanoparticles and the nanoparticle-entrapped DNA, and also determined p53
      mRNA levels over a period of time. Cells transfected with wt-p53 DNA-loaded
      nanoparticles demonstrated a sustained and significantly greater
      antiproliferative effect than those with naked wt-p53 DNA or wt-p53 DNA complexed
      with a commercially available transfecting agent (Lipofectamine). Cells
      transfected with wt-p53 DNA-loaded nanoparticles demonstrated sustained p53 mRNA
      levels compared to cells which were transfected with naked wt-p53 DNA or the wt
      p53 DNA-Lipofectamine complex, thus explaining the sustained antiproliferative
      activity of nanoparticles. Studies with fluorescently labeled DNA using confocal
      microscopy and quantitative analyses using a microplate reader demonstrated
      sustained intracellular localization of DNA with nanoparticles, suggesting the
      slow release of DNA from nanoparticles localized inside the cells. Cells which
      were transfected with naked DNA demonstrated transient intracellular DNA
      retention. In conclusion, nanoparticle-mediated wt-p53 gene delivery results in
      sustained antiproliferative activity, which could be therapeutically beneficial
      in cancer treatment.

PMID- 15981925
TI  - An insect antibacterial peptide-based drug delivery system.
AB  - The ability of the short, proline-rich native antibacterial peptides to penetrate
      bacterial and host cells suggests the utility of these transport systems in
      delivering peptidic cargo into cells. We studied the uptake of pyrrhocoricin and
      its most potent dimeric analogue by bacteria as well as human dendritic cells and
      fibroblasts. Native pyrrhocoricin entered the susceptible organism Escherichia
      coli very efficiently and the nonsusceptible bacterium Staphylococcus aureus to a
      significant degree. The antibacterial peptide also penetrated human monocyte
      derived dendritic cells. It failed, however, to enter fibroblasts, whereas the
      designer analogue Pip-pyrr-MeArg dimer penetrated all the cell types that were
      studied. When glucoincretin hormone Glp-1 fragment 7-36 was cosynthesized with
      the dimer, the antibacterial peptide derivative lost its ability to cross the
      bacterial membrane layer. In contrast, a chimera of the Pip-pyrr-MeArg dimer and
      two copies of a shorter (nine residues) class I major histocompatibility complex
      epitope successfully entered bacterial and mammalian cells. While the Pip-pyrr
      MeArg dimer was not immunogenic when inoculated into mice, the chimera elicited a
      strong cytotoxic T-cell response, indicating the maintenance of the antigenic
      integrity of the cargo in the peptide conjugate. The chimera when tested for its
      immunological properties activated human dendritic cells significantly more
      strongly than any of the two independent fragments alone, yet lacked mammalian
      cell toxicity. These results confirm the utility of designed pyrrhocoricin
      analogues for delivery of peptidic cargo across cell membranes in general, and
      their potential as carriers for epitope-based vaccines in particular.

PMID- 15981926
TI  - Micellar aggregation and membrane partitioning of bile salts, fatty acids, sodium
      dodecyl sulfate, and sugar-conjugated fatty acids: correlation with hemolytic
      potency and implications for drug delivery.
AB  - The co-administration of a drug with a penetration enhancer (PE) is one method by
      which the membrane permeability of a drug can be improved. To facilitate PE
      design, it is important that the molecular basis of PE toxicity and efficacy be
      examined, so we investigated the membrane affinity and micellar aggregation of a
      series of synthetic liposaccharide PEs and correlated these properties with
      hemolytic potency. The influence of liposaccharide alkyl chain length (nc) on the
      system was studied, and comparisons were made with conventional PEs such as bile
      salts, fatty acids, and surfactants. The liposaccharides were each synthesized in
      eight steps in good overall yield. Their critical micelle concentrations (CMCs)
      in phosphate-buffered saline ranged from 0.207 to 20.2 mM, and it was found that
      increasing nc by 2 afforded a 1 order of magnitude decrease in the CMC.
      Immobilized artificial membrane (IAM) chromatography was used to determine each
      PE's affinity for biological membranes, and an increase in nc caused a
      significant increase in the extent of membrane binding. A study of hemolytic
      activity revealed that liposaccharides with an nc of < or = 12 are the most
      likely to be biocompatible. The CMC values for all PEs showed a negative
      correlation with hemolytic potency; however, it was PE monomers, not micelles,
      that were responsible for the onset of hemolysis. The affinity of all enhancers
      for the IAM displayed a positive correlation with hemolytic potency, and
      therefore, IAM chromatography can be used to predict PE hemolytic activity. It
      was concluded that the biocompatibility of liposaccharides can be modulated by
      minor alterations in nc.

PMID- 15981928
TI  - [Digitalized imaging pathology: application to quality control in cancer
      diagnosis].
AB  - OBJECTIVES: To test a double histology reading system based on digitalized
      imaging for cancer diagnosis. MATERIAL AND METHODS: Pathology images of cancer
      diagnosis material were produced in real time by a digital imaging system
      integrated into the laboratory data processing system. Over a 30-day period,
      second readings were performed using the digitalized images. Cases with second
      readings were classified according to the aspect on the digitalized images as
      malignant tumor with histological type, malignant tumor with no other precision,
      and doubtful malignancy. RESULTS: During the study period, 204 cases of cancer
      were diagnosed, including 178 with digitalized imaging (87%). Among the
      digitalized cases, 119 (67%) were classified as malignant tumor with histological
      type, 53 (30%) as malignant tumor with no other precision, and 6 (3%) as doubtful
      malignancy. The histology material of these latter cases were reviewed and
      corresponded to malignant tumors. Approximately 2 hours per week were devoted to
      the second readings. CONCLUSION: A integrated digitalized imaging system can
      participate in quality control of cancer diagnosis by allowing rapid efficacious
      second readings.

PMID- 15981927
TI  - [Pathological and clinical correlations in primary cutaneous B-cell lymphomas: a
      series of 44 cases].
AB  - AIMS: histological and clinical relationship study of 44 cases of primary
      cutaneous B cell lymphoma, classified according to WHO classification. MATERIALS
      AND METHODS: histological, immunological and molecular analysis was correlated
      with clinical data. RESULTS: 33 cases (75%) were marginal zone B-cell lymphomas
      (MZL), with head and trunk predominance (median age = 54 years). Relapses in
      other mucosa-related sites occurred in 3 patients. Histological transformation
      implied a more aggressive treatment in 3 cases. A favorable outcome was observed
      in most cases. 9 (20%) diffuse large B-cell lymphomas (DLBCL) appeared as a
      unique nodule, with female predominance (median age = 74 years) and 4 lymphoma
      related deaths which seemed age-related (> 70 years) with only one lower limb
      localization. Histological aggressive features were present in 3 patients with a
      fatal outcome. 2 (5%) WHO grade 3 follicular lymphomas (FL) had an heterogeneous
      phenotype, with head localization, cutaneous relapses and good outcome.
      CONCLUSIONS: MZL, the predominant type, has a good prognosis, although
      transformation can occur, needing a more aggressive treatment. DLBCL, observed in
      older patients, has clinical and histological prognostic factors identical to
      extra-cutaneous lymphomas. FL appears rare and has an heterogeneous phenotype.
      Relationships with its nodal counterpart remains unclear.

PMID- 15981929
TI  - [Diagnostic value of anti-terminal deoxynucleotidyl transferase antibody (TdT) in
      hematologic pathology].
AB  - AIMS: The diagnosis of primitive hematologic malignancies depends on a panel of
      monoclonal antibodies which is growing over time. The distinction between
      immature (lymphoblastic lymphoma/acute lymphoblastic leukaemia) and mature
      lymphoma is sometimes difficult. In this study, we evaluated anti-TdT antibody in
      the diagnosis and classification of these proliferations. MATERIALS AND METHODS:
      13 lesions were examined by immunohistochemistry: 4 B and T lymphoblastic
      lymphomas, 2 Burkitt's lymphomas, 5 B and T acute lymphoblastic leukemias and 2
      acute monoblastic leukemias. RESULTS: TdT expression is specific of immature
      lymphoid proliferations (T or B lymphoblasts). TdT is not expressed by mature B
      or T cell lymphomas such as Burkitt's lymphomas. Significant numbers of cases of
      acute myeloblastic leukemias are TdT positive but could be easily distinguished
      from lymphoblastic proliferations. CONCLUSION: Anti-TdT antibody represents a
      useful marker for differentiating lymphoma/acute lymphoblastic leukemia from
      other lymphomas. This marker, available in routine diagnosis should be
      systematically included in the panel of antibodies used for immunophenotyping
      hematologic malignancies.

PMID- 15981930
TI  - [Which stem cells for adult liver?].
AB  - While hepatocytes can be considered conceptually as unipotent stem cells, the
      presence of true stem or progenitor cells within adult livers has been largely
      debated. It is now accepted that the atypical ductular reaction observed in
      livers with sub-massive hepatitis represents the proliferation of hepatic
      progenitor cells similar to rat oval cells and able to differentiate towards the
      biliary and the hepatocytic lineage through intermediate progeny. In the normal
      liver, the identification of progenitor cells with a panel of markers including c
      kit, CD34, Ov6, CK7, CK19, chromogranine A, CD56 remains difficult because these
      cells are very few and most of the markers are not specific. These progenitor
      cells could be located either within the canals of Hering or in periductular
      situation or both. Mechanisms leading to the activation and the proliferation of
      hepatic progenitor cells are still largely unknown: they involve growth factors
      as the stem cell factor, ligand of c-kit, cytokines, chemokines as SDF1 a and
      vagal or sympathetic innervation. Other potential stem cells for liver could be
      hematopoietic stem cells from bone marrow. First publications have showed that
      hematopoietic stem cells were able to differentiate into hepatocytes and
      cholangiocytes and to yield high level engraftment of injured livers. However it
      appears now that this phenomenon is minimal or even absent in physiological and
      usual pathological conditions. It does occur in extreme experimental conditions
      either by true transdifferentiation or cell fusion. The shared property of stem
      cells and tumor cells to proliferate endlessly, rises the question of the
      potential role of progenitor cells in liver carcinogenesis. In a number of animal
      models of hepatocarcinogenesis, tumors originate from oval cells. The
      identification of progenitor cells close to murine oval cells in the human liver
      raises the hypothesis of a potential role of these cells in the development of
      human liver tumors. Liver progenitor cells have been identified morphologically
      and phenotypically in dysplastic foci of cirrhotic livers and hepatocellular
      adenomas. More generally speaking, typical hepatocellular carcinomas and
      cholangiocarcinomas are at the two ends of a spectrum which includes transitional
      type tumors intermediate between hepatocellular carcinoma and cholangiocarcinoma
      and combined hepato-cellular cholangiocarcinoma; these intermediate and combined
      types can be more easily explained as deriving from progenitor cells. Despite the
      difficulties, the doubts and the potential dangers, new experimental modalities
      to obtain efficient repopulation of the liver from bone marrow stem cells are
      currently under study: exogenous administration of cytokines and chemokines
      involved in cell homing and differentiation or development of selective pressure
      strategies. Other cell types as intra-hepatic progenitor cells, bone marrow
      multipotent adult progenitor cells (MAPCs) or fetal hepatocytes could be
      alternative sources for liver cell therapy. Thus, progressing knowledge about
      stem cells in adult liver would allow to better understand mechanisms of hepatic
      homeostasia and regeneration and would open the way to cell-based therapy for
      liver diseases.

PMID- 15981931
TI  - [Plasmablastic lymphoma in a patient with HIV infection: an unusual case located
      in the skin].
AB  - We report the case of a plasmablastic lymphoma involving the skin in a 45 year
      old HIV-positive patient. Plasmablastic lymphoma was first described in 1997 and
      is considered to be a diffuse large B-cell lymphoma with a unique immunophenotype
      and a predilection for the oral cavity. In this case, the tumor was revealed by
      multiple purple cutaneous nodules predominantly localized on the trunk and
      proximal parts of the limbs. A skin biopsy led to the diagnosis of plasmablastic
      lymphoma in view of the presence of a dense nodular infiltrate invading the
      dermis and subcutaneous fat composed of large cells that expressed neither the
      leucocyte common antigen nor the B- and T-cell antigens CD20 and CD3, but which
      showed a strong immunostaining with plasma cell marker VS38c. Most of the cells
      expressed Kappa light chain of immunoglobulins, they did not express Lambda light
      chain. In situ hybridization with EBER probe revealed detection of Epstein Barr
      virus in about 15 % of tumor cells. The clinical course was aggressive and
      rapidly fatal. Despite one cycle chemotherapy the patient died four months after
      presentation. HIV-associated plasmablastic lymphoma is a poor prognosis
      malignancy that may resist typing due to the lack of expression of commonly used
      lymphoid markers.

PMID- 15981932
TI  - [Multicentric reticulohistiocytosis: report of a case with systemic disease].
AB  - Multicentric reticulohistiocytosis (RHM) is a rare non Langherhans cell
      histiocytosis with skin and joint involvment. Nearly all organs can be involved.
      Association with cancer occurs in about 25% of cases. Association with auto
      immune diseases has also been recorded. Microscopic examination shows a
      histiocytic nodular infiltrate made of giant cells with ground-glass appearance
      and PAS positive cytoplasm. Immunostaining shows cell positivity for CD68 and
      negativity for CD1a and S100 protein. No Birbeck granules are found at
      ultrastructural examination.

PMID- 15981933
TI  - [Superficial angiomyxoma: report of four cases, including two subungueal tumors].
AB  - We report four cases of superficial angiomyxomas, including two cutaneous tumors
      and two subungueal tumors. Histological analysis revealed a recently described
      tumor, so called superficial angiomyxoma. This is a myxoid paucicellular tumor
      lobulated and poorly circumbscribed, containing numerous small blood vessels
      surrounded by a mixed inflammatory cell infiltrate with notable neutrophils.
      Those tumors are positive for CD34. The differential diagnosis includes myxoid
      neurothecoma, myxoid neurofibroma and, for ungueal tumors, superficial acral
      fibromyxoma.

PMID- 15981935
TI  - [An unusual place for hepatocytes!].

PMID- 15981934
TI  - [Angiomyofibroblastoma of the male genital tract. Pathological and
      immunohistochemical study of three cases].
AB  - Angiomyofibroblastoma of the male genital tract is a rare tumor with only 20
      cases reported in the literature to date. We report three cases in males aged
      from 23 to 44 years. They presented with painless inguinal, scrotal and perineal
      masses, ranging from 3 to 8 cm in diameter. On microscopic examination the tumors
      were composed of small spindle cells without atypia in a fibrous and myxoid
      stroma. There were scattered mononuclear inflammatory cells around capillaries.
      Immunohistochemical studies showed positive staining of the tumor cells for
      vimentin, and weak reactivity for CD34, bcl-2, CD99, EMA and CD117. Some tumor
      cells expressed estrogen receptors in all three cases, and progesterone receptors
      in only one case. There was no recurrence with a follow-up ranging form 12 to 21
      months. Angiomyofibroblastoma of the male genital tract is a benign often hormone
      dependent tumor. Its histogenesis is still unclear. It has to be distinguished
      from aggressive angiomyxoma and myxofibrosarcoma.

PMID- 15981936
TI  - [Cancer stem cells: new insights].

PMID- 15981937
TI  - [A calcified subcutaneous tumor].

PMID- 15981938
TI  - [A peculiar case of anal polyp].

PMID- 15981939
TI  - [An unusual tumor of the liver].

PMID- 15981940
TI  - [A breast tumor to recognize].

PMID- 15981941
TI  - Clinical use of pegvisomant for the treatment of acromegaly.
AB  - Understanding the mechanisms by which growth hormone (GH) interacts with its
      receptor has led to the design of compounds that function as GH receptor
      antagonists. One such compound has been conjugated to polyethylene glycol (PEG)
      to produce a drug, pegvisomant, which has been extensively investigated as a
      treatment for acromegaly. It was recently approved for clinical use in the US and
      will shortly be available on prescription in Europe. Studies have shown that the
      drug is able to normalize circulating levels of insulin-like growth factor-1 (IGF
      1), the principal mediator of GH action, in 97% of patients with active
      acromegaly, as well as improve the symptoms and signs associated with GH excess.
      Serum IGF-1 levels have been used as the chief marker of efficacy of treatment
      with pegvisomant. The drug is able to achieve biochemical control in patients
      wholly or partially resistant to somatostatin analogs. Preliminary data suggests
      that pegvisomant may be a particularly suitable choice of medical therapy for
      patients with acromegaly and coexistent diabetes mellitus.

PMID- 15981942
TI  - Childhood overweight: an expanding problem.
AB  - Childhood overweight is a significant and growing health problem in the US and
      other parts of the world. Secular trend data in the US suggest that children have
      become substantially heavier over the last several decades and that their risk
      for a number of health problems is increasing as a result. Defining obesity in
      children has been difficult as assessing body fat is expensive and impractical.
      Body mass index (BMI), derived from weight and height, is used as a surrogate
      indicator in adults. In children, the consensus is to use BMI percentiles
      statistically derived from a reference population. There is evidence that the
      prenatal, early childhood, and adolescent periods are critical in the development
      of obesity but the mechanisms involved are yet to be elucidated. The recent rapid
      increase in childhood overweight and obesity is attributed to the modern
      obesogenic environment. Changes in dietary constituents including higher
      derivation of energy from nutritionally poor and energy dense foods, increased
      sweetened drink consumption, larger portion sizes, and more frequent intake of
      food outside the home have been associated with poorer diets and higher weights.
      Further, physical activity has reduced with decreases in school physical
      education classes and organized sports, fewer opportunities to expend energy for
      daily living activity due to more mechanization, lower frequency of walking and
      biking, and greater use of sedentary activities for leisure. Television watching
      remains the most common activity for children. There are significant health
      outcomes associated with childhood obesity, including the presence of
      cardiovascular risk factors, and greater prevalence of various medical problems
      including insulin resistance, type 2 diabetes mellitus, the metabolic syndrome,
      orthopedic problems, and pseudotumor cerebri. Of further concern is the increased
      risk for obesity in adulthood with its attendant co-morbidities. Interventions
      are imperative but not widely studied. The most effective interventions include
      comprehensive behavioral management, dietary modification, and exercise. Family
      based interventions have been most successful at maintaining long-term weight
      loss. School-based interventions have the potential to significantly impact
      childhood overweight as large numbers of children can be reached. However, such
      programs require long-term follow-up and are expensive. Very low calorie diets,
      pharmacotherapy, and surgery remain experimental options for children. More
      recently, metformin has shown promise in promoting weight loss and improving
      insulin sensitivity among adolescents. Combining multiple approaches for
      treatment, addressing obesity-promoting sociocultural practices and policies, and
      focusing on prevention strategies will be necessary to address this epidemic.

PMID- 15981943
TI  - Current and future strategies for the management of diabetic neuropathy.
AB  - Diabetic neuropathy is common, related to increased morbidity and mortality, and
      has no effective treatment at present. Interventions based on putative pathways
      thought to contribute to damage and repair of nerve fibres have yielded little
      success to date. Pain is a potentially debilitating manifestation of diabetic
      neuropathy and has many potential sites of origin and, hence, modulation. Its
      cause is unclear and it does not respond well to traditional pain therapies,
      proposed to mediate their benefits via multiple peripheral and central
      mechanisms. A better understanding of the mechanisms leading to nerve fibre
      degeneration and regeneration as well as pain has recently resulted in the
      development of a more targeted approach to the treatment of diabetic neuropathy.
      Thus, specific NMDA receptor antagonists and more specific neuronal serotonin and
      norepinephrine (noradrenaline) uptake inhibitors offer promise in the treatment
      of painful diabetic neuropathy. A number of treatments which include the aldose
      reductase inhibitors and neurotrophins have failed to reach the clinical arena.
      However, the antioxidant alpha-lipoic acid, as well as compounds which correct
      vascular dysfunction and hence neuropathy, such as ACE inhibitors and protein
      kinase C-beta inhibitors, have demonstrated more success.

PMID- 15981944
TI  - Pharmacology of the meglitinide analogs: new treatment options for type 2
      diabetes mellitus.
AB  - The expression meglitinide analogs was introduced in 1995 to cover new molecules
      proposed as non-sulfonylurea insulinotropic agents and displaying structural
      analogy with meglitinide, such as repaglinide, nateglinide, and mitiglinide.
      Meglitinide analogs display, as judged by conformation analysis, a U-shaped
      configuration similar to that of antihyperglycemic sulfonylureas such as
      glibenclamide (glyburide) and glimepiride. In rat pancreatic islets incubated in
      the presence of 7.0 mmol/L D-glucose, repaglinide and mitiglinide demonstrate
      comparable concentration-response relationships for stimulation of insulin
      release, with a threshold value < 10 nmol/L and a maximal secretory response at
      about 10 nmol/L. Several findings indicate that meglitinide analogs provoke the
      closing of adenosine triphosphate-sensitive potassium channels, with subsequent
      gating of voltage-sensitive calcium channels. The effects of meglitinide analogs
      upon the binding of [3H]glibenclamide to islet cells membranes reinforces this
      concept. At variance, however, with other meglitinide analogs, the ionic and
      secretory response to repaglinide (10 micromol/L) is not rapidly reversible in
      perifused rat islets. In experiments conducted in vivo in control and diabetic
      rats, repaglinide provokes a greater and more rapid increase in plasma insulin
      concentration and an earlier fall in glycemia than glibenclamide or glimepiride.
      Onset of effect is also more rapid and duration of effect shorter with
      nateglinide versus glibenclamide. In clinical studies, single or repeated daily
      administration of repaglinide increased plasma insulin concentration in a dose
      dependent manner, with an incremental peak reached about 2 hours after
      repaglinide intake. Plasma concentrations of repaglinide are about 5.0 microg/L 2
      2.5 hours after oral intake of the drug. Despite the slow reversibility of
      repaglinide action in vitro, this drug offers advantages over glibenclamide in
      terms of the possible occurrence of hypoglycemia if a meal is missed. In
      volunteers receiving a single oral dose of nateglinide (120mg) 10 minutes before
      a standardized 800 Kcal breakfast, the plasma insulin concentration was higher 5,
      10, and 20 minutes after meal intake than when they received a single dose of
      repaglinide (0.5 or 2.0mg) or placebo 10 minutes before breakfast. Peak plasma
      concentrations of nateglinide were reached within 2 hours in most volunteers.
      Peak plasma concentrations of mitiglinide were reached 30 minutes after a single
      oral dose in a representative volunteer. Mitiglinide significantly suppressed
      meal-induced elevations in blood glucose concentrations in a study of patients
      with type 2 diabetes. In conclusion, two obvious differences among these
      meglitinide analogs should be underlined. First, on a molar basis, nateglinide is
      somewhat less potent than repaglinide or mitiglinide, as an insulinotropic agent.
      The maximal secretory responses evoked by these three meglitinide analogs are,
      however, identical to one another. Secondly, and as already mentioned, the
      functional effects of nateglinide and mitiglinide are more rapidly reversible
      than those of repaglinide, for instance in perifused rat islets. The meglitinide
      analogs offer the advantage over the long-acting antihyperglycemic sulfonylurea
      glibenclamide of minimizing the risk of undesirable hypoglycemia.

PMID- 15981945
TI  - Risedronate once a week.
AB  - Risedronate (risedronic acid), an orally administered pyridinyl bisphosphonate,
      inhibits osteoclast-mediated resorption of bone and modulates bone metabolism in
      women with postmenopausal osteoporosis. The long terminal exponential half-life
      of risedronate (480 hours) has led to the development of a 35mg tablet for once-a
      week administration. The beneficial effects of risedronate 35mg once a week on
      total hip, femoral neck and trochanter bone mineral density (BMD) at 12 months
      were similar to those of risedronate 5mg once daily. Risedronate 35mg once a week
      was as effective as risedronate 5mg once daily in improving lumbar spine BMD in a
      randomized, double-blind, multicenter trial of 1456 women with postmenopausal
      osteoporosis. Mean percentage increases in BMD from baseline at 12 months were
      3.94% and 4.25% in the 35mg and 50mg once-a-week dose groups, compared with 4% in
      the 5mg once-daily dose group. The differences between the once-a-week doses and
      the once-daily dose met the predetermined criterion for non-inferiority. An
      historical analysis suggested that risedronate 35mg once a week reduced the
      incidence of vertebral fracture significantly more than placebo. The tolerability
      profile (including the incidence of upper gastrointestinal adverse events) of
      risedronate 35mg once a week in women with postmenopausal osteoporosis, was
      similar to that of risedronate 5mg once daily.

PMID- 15981946
TI  - Mechanisms underlying endothelial dysfunction in diabetes mellitus: therapeutic
      implications.
AB  - Hyperglycemia is the major causal factor in the development of endothelial
      dysfunction in patients with diabetes mellitus. Although the mechanisms
      underlying this phenomenon are likely to be multifactorial, recent in vivo and in
      vitro studies have indicated a crucial role of the diacylglycerol (DAG)-protein
      kinase C (PKC) pathway in mediating this phenomenon. PKC may have multiple
      adverse effects on vascular function, including the activation of superoxide
      producing enzymes such as the nicotinamide adenine dinicleotide phosphate (NADPH)
      oxidase as well as increased expression of a dysfunctional, superoxide-producing,
      uncoupled endothelial nitric oxide synthase (NOS III). PKC-mediated superoxide
      production may inactivate nitric oxide (NO) derived from endothelial NOS III, but
      also may inhibit the activity and/or expression of the NO downstream target, the
      soluble guanylyl cyclase. Among the different isoforms of PKC, mainly the beta
      isoforms have been shown to be activated. Recent studies with selective (isoform
      specific) and non-selective PKC inhibitors show that they are able to
      beneficially influence glucose-induced endothelial dysfunction in experimental
      animal models as well as in patients, pointing to the therapeutic potential of
      these compounds in the prevention and treatment of vascular complications of
      diabetes.

PMID- 15981947
TI  - Does the addition of luteinizing hormone in ovarian stimulation protocols improve
      the outcome?
AB  - Ovarian stimulation is an integral part of assisted reproductive technologies
      (ART). Under physiologic conditions, both follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH) activity is necessary to guarantee follicle growth and
      maturation. This can be shown in patients with hypogonadotrophic hypogonadism,
      who have no endogenous FSH or LH activity. The use of FSH alone in these patients
      does not result in sufficient follicle growth and oocyte quality. Approximately
      75IU of LH activity per day is necessary to guarantee optimal success. The use of
      gonadotropin-releasing hormone (GnRH) agonists in normogonadotrophic patients may
      result in suppression of LH levels below a certain threshold, resulting in
      suboptimal outcomes. The question under discussion in this article is the
      threshold level of LH below which exogenous LH activity should be added to
      provide optimal ovarian response. Different studies indicate that the endogenous
      LH level should be 0.5-1.5IU in long-term protocol situations. Patients treated
      in ultra-long GnRH agonist protocols, as well as older patients, patients with a
      low response to gonadotropin treatment, and patients treated with a GnRH
      antagonist protocol may benefit from exogenous LH activity. There are three ways
      of adding LH activity in ovarian stimulation cycles. Nowadays, lutropin alfa
      (recombinant LH) may be the optimal choice since it has no chorionic gonadotropin
      activity and allows individual dosage titration. Every menotropin preparation
      currently on the market contains some chorionic gonadotropin activity. However,
      more data are necessary before evidence-based recommendations regarding LH
      supplementation in ovarian stimulation protocols can be given.

PMID- 15981948
TI  - Lifestyle intervention for the prevention of type 2 diabetes mellitus: putting
      theory to practice.
AB  - Type 2 diabetes mellitus is a serious, growing, and costly public health problem.
      The disease is chronic and degenerative, and thus primary prevention is
      desirable. Observational studies have linked type 2 diabetes to specific
      lifestyle behaviors. Several recent major clinical trials confirm that type 2
      diabetes can be delayed or prevented in people at high risk; multicomponent
      lifestyle modification can reduce the incidence of diabetes up to 58%. The
      American Diabetes Association has recently recommended that lifestyle
      interventions to prevent or delay diabetes be delivered to people with
      prediabetes. Delivery of lifestyle interventions in practice is fraught with
      challenges, but there are several tools and practical strategies available for
      the implementation of trial findings.

PMID- 15981949
TI  - Hormonal contraception in women with diabetes mellitus: special considerations.
AB  - Contraception is an important issue for women with diabetes mellitus as unplanned
      pregnancy can present major maternal and perinatal complications. The rising
      incidence of diabetes worldwide means increasing thought needs to be given to
      contraceptive options for these women. This article reviews current evidence and
      recommends best practice for prescribing hormonal contraceptives in women with
      diabetes. Women with diabetes have the same choice of contraceptives as the
      general population, but the potential metabolic effects of hormonal methods need
      to be considered in relation to an individual's diabetic profile and their need
      for effective contraception. Currently, there appear to be wide variations in the
      way that professionals evaluate the risk-benefit equation, and significant
      differences in prescribing practice have been identified. The World Health
      Organization (WHO) has established medical eligibility criteria to assist in
      assessing such risks. Cardiovascular disease is a major concern, and for women
      with diabetes who have macrovascular or microvascular complications, nonhormonal
      methods are recommended. Studies of young women with diabetes and no vascular
      changes who are taking low-dose combined oral contraceptives (COCs) have been
      reassuring, although larger long-term studies are needed. There is little
      evidence that any changes in glycemic control caused by COCs are of clinical
      relevance. While low-dose COCs appear to cause minimal change in the lipid
      profile and may even be beneficial in this respect, there are some concerns in
      relation to progestogen only pills and injectable contraceptives in certain
      women. There is little evidence of best practice for the follow-up of women with
      diabetes prescribed hormonal contraception. It is generally agreed that blood
      pressure, weight, and body mass index measurements should be ascertained, and
      blood glucose levels and baseline lipid profiles assessed as relevant. Research
      on hormonal contraception has been carried out in healthy populations; more
      studies are needed in women with diabetes and women who have increased risks of
      cardiovascular disease.

PMID- 15981950
TI  - Prevention and treatment of postmenopausal osteoporosis.
AB  - Osteoporosis is a systemic disease characterized by low bone mass and
      microarchitectural deterioration of the skeleton leading to enhanced bone
      fragility and an increased risk of fracture. Prior to fracture, diagnosis is
      established by documenting low bone mass. In the first section of this article we
      review the clinical use of bone mass measurements and biochemical markers of bone
      remodeling in selecting patients most in need of preventive therapy at menopause.
      Women with high bone turnover lose bone at menopause more rapidly than those with
      normal bone turnover and are more likely to derive benefit from the several
      preventive therapies available. The second section addresses the available
      technologies used to diagnose osteoporosis and/or establish fragility fracture
      risk using noninvasive bone mass measurement and biochemical markers of bone
      remodeling separately or in combination. In the third section we review the
      several treatment options available for patients with osteoporosis, including
      alendronate (alendronic acid), risendronate (risedronic acid), calcitonin,
      teriparatide, and raloxifene, and the approaches to monitoring the therapeutic
      response. The final section deals with fall protection--an often forgotten aspect
      of management of the patient at risk for sustaining and osteoporotic fragility
      fracture.

PMID- 15981951
TI  - Influence of growth hormone on cardiovascular health and disease.
AB  - Experimental and clinical studies indicate that growth hormone (GH) and insulin
      like growth factor-1 (IGF-1) are involved in heart development. Impaired
      cardiovascular function, as recently demonstrated, could potentially reduce life
      expectancy both in GH deficiency (GHD) and excess. Patients with childhood- or
      adult-onset GHD may have both cardiac structural and functional abnormalities,
      i.e. reduced cardiac mass, reduced diastolic filling, and impaired left
      ventricular response to peak exercise. In addition, GHD patients may present with
      an increase in vascular intima-media thickness and a higher occurrence of
      atheromatous plaques that can further aggravate the hemodynamic conditions and
      contribute to the increased cardiovascular and cerebrovascular risk. However,
      some evidence has been provided to show that cardiovascular abnormalities can be
      partially reversed after somatropin (recombinant GH) therapy in patients with
      GHD. Recently, somatropin administration was shown to induce improvement in
      hemodynamics and clinical status in some patients with heart failure. Although
      these data need to be confirmed in more extensive studies, such promising results
      open new perspectives for somatropin therapy. The role of GH secretagogues in
      heart failure is still unknown.

PMID- 15981952
TI  - Gestational diabetes: a review of the treatment options.
AB  - More than three decades since the original published description of gestational
      diabetes mellitus (GDM), no consensus exists regarding its implications or
      management. Targeting fetal macrosomia as the greatest morbidity, treatment
      strategies for this pregnancy-induced disease of insulin resistance have largely
      been modeled from therapies proven successful in pregnant women with type 2
      diabetes mellitus. Surrounded by a rapidly expanding array of treatment options
      for insulin-resistant diabetes, potentially legitimate concerns about
      teratogenicity and fetal metabolic effects have limited clinical trials of
      insulin analogs and oral antihyperglycemic agents during pregnancy. So far, only
      insulin lispro and glyburide (glibenclamide) have been tested prospectively in
      randomized trials of women with GDM. In limited studies, both of these agents
      have compared favorably with standard insulin regimens, and neither appear to
      cause any fetal or neonatal harm. Although acknowledged by the American Diabetes
      Association (ADA) and the American College of Obstetricians and Gynecologists
      (ACOG), these seminal studies have not yet prompted a recommendation from either
      organization on how to utilize insulin analogs or oral antihyperglycemic agents
      in the treatment of GDM. Although they lack an evidence base for many therapeutic
      strategies for GDM, the current ADA and ACOG guidelines still provide a
      reasonable set of treatment recommendations.

PMID- 15981953
TI  - [Attitude before COX-2 selective inhibitors].

PMID- 15981954
TI  - [Effect of preoperative biliary drainage on surgical outcome after
      pancreatoduodenectomy].
AB  - BACKGROUND/AIM: There are theoretic arguments in favor and against biliary
      drainage before the pancreatoduodenectomy. Most of the studies failed to show any
      beneficial effect of this approach whereas others even reported an increased
      postoperative morbidity related with biliary drainage. Therefore, the role of
      preoperative biliary drainage remains controversial. So, we decided to analyze
      our own results in a series of patients undergoing pancreatoduodenectomy in order
      to determine the association between preoperative biliary drainage and
      postoperative outcome. PATIENTS AND METHODS: We analyzed 109 patients undergoing
      pancreatoduodenectomy between January 1990 and May 2003. Patients were classified
      in 3 groups: Group 1 (n = 64) patients without preoperative biliary drainage,
      Group 2 (n = 27) patients who underwent preoperative biliary drainage with
      sphincterotomy and stent placement, and Group 3 (n = 18) only sphincterotomy.
      Demographic characteristics, surgical risk, comorbility, type of surgery,
      pathology and biochemical parameters were analyzed. We also, stratified patients
      with and without cholestasis (total bilirubin > 3 mg/dL), and divided patients in
      two groups: with biliary drainage and without biliary drainage. Surgical and
      medical complications, the frequency of patients with at least one complication
      (global morbidity) and mortality were compared between groups. Kruskal-Wallis,
      Mann-Whitney U, chi2 and Fisher tests were used for the analysis of categorical
      and dimensional variables. RESULTS: The most frequent postoperative diagnoses
      were biliopancreatic tumors. Global postoperative morbidity and mortality were
      40% (n = 44) and 10% (n = 11), respectively. The frequency of surgery and medical
      complications were no significantly different among the 3 groups. However, when
      only patients with cholestasis were analyzed (n = 65), there was a lower
      frequency of surgical complications and global postoperative morbidity in
      patients with preoperative biliary drainage (p = 0.02, OR 0.14, CI 95% 0.04-0.50
      and p < 0.001, OR 0.18, CI 95% 0.05-0.65, respectively). There were not
      significant differences in the frequency of medical complications (p = 0.09) and
      mortality. CONCLUSIONS: Preoperative biliary drainage should not be considered as
      a routine procedure in candidates undergoing pancreatoduodenectomy; however, this
      maneuver decreased approximately seven times the risk of postoperative global
      morbidity in patients with cholestasis, mainly by reducing surgical complications
      reduction.

PMID- 15981955
TI  - [The subjective visual vertical in vestibular disease].
AB  - OBJECTIVE: To assess and compare the accuracy to perceive visual verticality,
      with and without trunk-head tilt in the frontal plane (30 degrees), in patients
      with peripheral or central vestibular disease. METHODS: Thirty eight patients
      accepted to participate, 23 with peripheral disease and 15 with central disease.
      We also evaluated 40 healthy subjects. Subjects were seated facing a screen with
      an anchored motorized bar (20 cm). They were asked to bring the line to vertical,
      using a joystick, 10 times while seated upright and 10 times while tilted 30
      degrees to each side. An average of the distance from true vertical was
      calculated to determine the tilt of the visual vertical on each posture. RESULTS:
      Always, estimations made by healthy subjects were < 2 degrees from true vertical.
      In patients, in upright posture the largest tilt of the visual vertical was
      observed in patients with peripheral disease and spontaneous nystagmus. However,
      in all patients the accuracy to estimate the true vertical decreased when they
      were evaluated with trunk-head tilt (p < 0.05). In this condition the sensitivity
      of the test increased from 34 to 85% and the efficacy from 68 to 93% (p < 0.05).
      CONCLUSION: Trunk-head tilt in the frontal plane decreases the accuracy of
      patients with vestibular disease to visually perceive verticality. This finding
      shows that head-trunk tilt can improve the sensibility and efficacy of this test
      to assess the vestibular function.

PMID- 15981956
TI  - Applicability of the National Cholesterol Education Program III (NCEP-III)
      guidelines for treatment of dyslipidemia in a non-Caucasian population: a Mexican
      nation-wide survey.
AB  - We assessed the impact of the NCEP-III recommendations in a population-based,
      nation-wide Mexican survey. Information was obtained from 15,607 subjects aged 20
      to 69 years. In this report, only samples obtained after a 9 to 12 hours fast are
      included (2,201 cases). A cardiovascular risk equivalent was found in 10.5% and >
      or = 2 risk factors were present in 41.7% of the population. In 10% of cases, the
      LDL-C concentration was high enough to be an indication for a lipid-lowering drug
      (> 160 mg/dL), independent of the presence of risk factors. A quarter of the
      population was eligible for some form of treatment (lifestyle modifications in
      15.9%, drug therapy in an additional 11.7%). Among cases with > or = 2 risk
      factors, a small percentage (1.8%) were identified as having a 10 year-risk > 20%
      and 86.3% were considered as having a 10 year-risk < 10%. The majority of the
      metabolic syndrome cases (84%) were identified as low-risk subjects. As a result,
      only 17.6% of them qualified for drug-based LDL-C lowering. Our data helps to
      estimate of the magnitude of the burden imposed on the Mexican health system, of
      lowering LDL-C for cardiovascular prevention. If we apply our results to the
      2,000 Mexican population census more than 5.8 million cases nationwide may
      require LDL lowering drug therapy following the NCEP-III criteria.

PMID- 15981957
TI  - [Population pharmacokinetics of carbamazepine in adults with epilepsy].
AB  - The aim of the present study was to determinate the factors affecting
      carbamazepine (CBZ) clearance (CL) in adults with epilepsy using a mixed-effect
      model and sparse data collected during routine clinical care. The patient
      population comprised 104 adults receiving CBZ. A total of 161 CBZ steady state
      serum concentration samples were analyzed. Population CL was calculated by using
      NONMEM with a one compartment model with first-order absorption and elimination.
      The following covariates were tested for their influence on clearance (CL): total
      body weight, age, dose/day, sex, surface area (SA) and comedication with
      primidone (PRIM), ualproic acid or phenytoin (DFH). The final regression model
      for carbamazepine clearance found best to describe the data was: CL = (0.614 SA +
      0.0016 dose/day)(1 + 0.278 DFH)(1 + 0.326 PRIM).

PMID- 15981958
TI  - Sentinel lymph node biopsy in colorectal cancer: a pilot study.
AB  - BACKGROUND: Although sentinel lymph node biopsy technique is the gold standard in
      the management of malignant melanoma and is gradually replacing conventional
      axillary dissection in breast cancer, its use in colorectal cancer is still
      controversial. The objective of this study is to demonstrate the feasibility and
      safety of sentinel node biopsy in the management of colorectal carcinoma.
      METHODS: Consecutive patients with colorectal carcinoma without preoperative
      evidence of nodal or distant metastatic disease were included. Intraoperative
      subserosal injection of 1 mL of isosulfan blue (Lymphazurin) was performed around
      the tumor in cases of colon cancer and ex-vivo infiltration was used for rectal
      cancer after resection was completed. Blue stained nodes were dissected and
      submitted for routine pathology exam. If nodes were deemed negative for neoplasm,
      immunohistochemistry for cytokeratin was performed. The specimen and non-stained
      nodes were resected and processed in the usual fashion. Sensitivity and negative
      predictive value were calculated and adverse effects to the blue dye were
      registered. RESULTS: Ten patients were included with at least one sentinel lymph
      node identified in each. Mean number of sentinel and non-sentinel lymph nodes
      were 2.5 and 15.6 per patient, respectively. The sensitivity and negative
      predictive value of the sentinel node after immunohistochemistry were both 100%.
      There were no adverse effects caused by the dye. CONCLUSIONS: Sentinel lymph node
      biopsy technique in colorectal cancer is feasible, has a high diagnostic accuracy
      and is harmless.

PMID- 15981959
TI  - [Plant lectins and their effects on cancer].
AB  - Recently, there has been increased interest in the potential health benefits of
      plant lectins, particularly due to their anticancer effect. This updated review
      discusses literature data published on the anticancer activities of plant lectins
      and their possible molecular mechanism(s) of action.

PMID- 15981960
TI  - [DRD4 polymorphism and the association with mental disorders].
AB  - The dopamine D4 receptor (DRD4) is the most important gene in psychiatric
      genetics since its involvement in the physiology of behavior, pharmacology
      response and psychopathology. DRD4's sequence gene present some polymorphism such
      as in the exon 3 constituted from 2 to 10 copies of repetitive sequences of 48
      base pair (bp), from class variable number tandem repeats (VNTR). An additional
      genetic variant in the exon 1 presents polymorphisms to 12 bp VNTR, and the
      variation -521 C by T of the promoter region. The -521 T allele can reduce the
      efficiency of the gene expression in comparison with the C allele. The DRD4 gene
      codes a protein transmembranal of 7 domains, distributed in front cortex,
      striatum, hypothalamus and hippocampus. This review discusses the biological
      significance of DRD4 gene and its perspective with emphasis on the impact of
      association studies in some illness mental and behavioral traits. The DRD4
      polymorphism has been studied in association with illnesses like schizophrenia,
      attention deficit hyperactivity disorder (ADHD), obsessive-compulsive with tics,
      bipolar manic-depressive disorder, in addition behavioral traits such as novelty
      seeking. The DRD4 gene is a genetic marker that could play a role in etiology of
      different mental illness, and behavioral traits, and its polymorphism can be used
      in association studies, epigenetic and pharmacogenomic analysis for help to
      understand the genetics basis of both mental disorders and traits.

PMID- 15981961
TI  - [Stomach endocrine neoplasias].

PMID- 15981962
TI  - [Diabetes and tuberculosis: in the labyrinth of the subdevelopment].

PMID- 15981963
TI  - [Evolution of the knowledge on the blood and its movement. Part two. The
      knowledge about its composition. Iatrochemistry of the blood].
AB  - To know the composition of blood and the benefits rendered by its components to
      life has been a question that for centuries stimulated the curiosity of
      researchers. Each of the human knowledge eras has provided its own explanation
      and gradually contributed with a series of discoveries, which by accumulating,
      have allowed to explain the physiological processes of this fluid, considered
      like vital since the most remote times. From being one more of the four humors
      that constitute living matter, according to ancient medicine, blood became,
      during seventeenth century, a mixture of fluids and diverse particles moved
      incessantly by the action of the heart. Once the iatromechanical aspect of blood
      circulation was known, the researchers approached the problem of its composition,
      using the new scientific tools (observation, experimentation and measurement),
      such as the microscope, quantification instruments, stains and chemical reagents,
      that appeared during the Baroque Period and later. During seventeenth century
      erythocytes were discovered as well as the metallic nature of blood when iron
      particles were detected in it. In the eighteenth century, leukocytes were
      discovered and, almost a century later, platelets were added. One of the great
      mysteries to solve, the coagulation of the blood, began to be deciphered in the
      seventeenth century, when fibrin was observed in the structure of the clots.
      Thrombin and tissue factor was discovered during nineteenth century. At the
      beginnings of the twentieth century, the morphology and origin of blood cells
      became known, as well as their variations during some diseases. The bases for the
      clinical laboratory, the hematology clinic and some therapeutic procedures, such
      as blood transfusion, developed. Separation of plasma components, cellular
      identification techniques, inheritance laws, and the talent to construct
      instruments for ever increasing precise analyses gave rise to the numerous
      specialties in science that has studied the blood: Hematology, Immunology,
      Clinical Biochemistry, Clinical Pathology, Hemostasis and Thrombosis,
      Transfusional Medicine, Hematogenetics, Chemotherapy and many others.

PMID- 15981964
TI  - [Antonio Ramos-De la Medina comments made to Uscanga's paper].

PMID- 15981965
TI  - [Aaron Sulkes' comments made to Uscanga's paper].

PMID- 15981966
TI  - [Chinese medicine: a new tradition].

PMID- 15981967
TI  - [Chinese phytotherapy: the power of synergy].
AB  - Chinese pharmacology is ancient and very extensive. In reality, Chinese
      pharmacology is composed of matter having vegetable, animal and mineral origins;
      however, the dominance of vegetable and the exclusive restriction to vegetable
      matter which European legislation obliges us to follow makes the use of the term
      phyto-therapy which means curing via plants, as is reported in another article,
      "Phyto-therapy, a choice based on science and tradition" by Dr. Josep
      AlluPeCreus. (Rev ROL Enf 8(3):179-182).

PMID- 15981968
TI  - [Acupuncture: intense and gentle stimulation].
AB  - As acupuncture does, we should establish a set of techniques through which one's
      metabolism is influenced by stimulating some specific zones from the outside. The
      usual stimulation methods are via puncture--the best known form of acupuncture--,
      pressure, energy concentration with or without the use of instruments, heat,
      electricity and magnetic agents.

PMID- 15981969
TI  - [Auricle therapy].
AB  - Auricle therapy is the method which diagnoses and treats the human body via the
      external ear. The author describes its simple application as its principal
      characteristics and contrasts these with the efficiency of its results.
      Furthermore, the author provides a wide range of therapeutic possibilities.

PMID- 15981970
TI  - [Tui-Na, an oriental massage].
AB  - Tui-Na is an oriental massage whose principles are based on traditional Chinese
      medicine. This medicine conceives a person as one entire entity giving as much
      importance to emotional and physical aspects as to everything that surrounds a
      person, including climate, social relationships, diet. This philosophy believes
      that an individual will achieve his/her ideal health state when he/she has found
      interior harmony and is in balance with all his/her environment. From this
      viewpoint, this philosophy understands pathology as an unbalance or a lack of
      harmony in an organism. Tui-Na massage is one of the techniques which make use of
      traditional Chinese medicine to maintain, or to recuperate, an organism's
      balance.

PMID- 15981971
TI  - [Qi Gong: medicine or enlightenment?].
AB  - According to Dr. Yang Jwing-Ming, the translation for Qi Gong would be "Whatever
      practice or study related with Qi which requires a lot of time and effort". Qi
      Gong is a practice which combines posture exercises, gestures, breathing and a
      mental attitude destined to make Qi circulate in order to preserve one's health,
      cure diseases and prolong life.

PMID- 15981972
TI  - [Floral essences, a fascinating world].
AB  - Floral essences were discovered in the decade of the thirties by the English
      doctor, bacteriologist and homeopath Dr. Edward Bach. He described 38 remedies
      elaborated with flowers and shoots; each one correspondeds to an emotional
      pattern or a typical personality. Furthermore, he describes a remedy developed
      for emergency situations.

PMID- 15981973
TI  - [What is aromatherapy?].
AB  - Aroma therapy is a natural technique based on the use of essential oils extracted
      from fresh plants for a therapeutic purpose. The substances used in aroma therapy
      are not fragrances or aromatic mixtures used in the perfume industry but pure
      essential oils, volatile substances extracted from diverse parts of plants which
      have curative property. Therefore, not everything which emits a pleasant smell is
      necessary an essential oil. Frequently used as a synonym for essential oil is the
      term essence which means a natural aromatic substance which a plant secretes from
      its reproductive organs; on the other hand, an essential oil is an extract
      obtained by distilling an essence.

PMID- 15981974
TI  - [Topical chemotherapy for the treatment of burns].
AB  - A burn is a tissue lesion which provokes different alterations that vary from
      topical erythema to total destruction of the structures affected. A burn always
      produces an alteration in the skin, a lesion in the corneal strata is sufficient
      to cause the skin to lose its capacity to act as a barrier. The objective the
      treatment for a burn has is to produce epithelization as soon as possible in
      order to prevent infection and to reduce functional and esthetic aftereffects.
      Infection is the main cause of death due to burns due to the growth of endogenous
      flora or due to external contamination. The use of topical chemotherapy is
      fundamental to prevent infections when there are deep and superficial burns or
      extensive intermediary burns. Centella asiatica extract has proven to be
      efficient in helping, maintaining and regularizing cicatrisation of skin affected
      by burns. Its usage combined with an antibiotic agent such as neomycin covers the
      bacterial spectrum for gram-positive or -negative microorganisms, guaranteeing an
      anti-infectious efficiency for this extract.

PMID- 15981975
TI  - Did nurses 'stonewall' parents of dead infant?

PMID- 15981976
TI  - Nurse terminated for meds. error: hospital attempts to deny access to records.
      Case on point: Chapman v. Health & Hospital Corporations, 2005 WL 697435--NY.

PMID- 15981977
TI  - MN: Nurse fired for sexual interaction with pt.: unemployment benefits denied.

PMID- 15981978
TI  - Failure to follow dr.'s orders: post-op orthopedic pt. injured. Case on point:
      Redel v. Capital Region Medical Center, 2005 WL 1084105 S.W.3d--MO.

PMID- 15981979
TI  - [60th anniversary of the founding of the 4th Internal Medicine Clinic].

PMID- 15981980
TI  - [Pathophysiology of and clinical significance of polyunsaturated fatty acids n-3
      family].
AB  - Polyunsaturated fatty acids of n-3 family play an important role in the
      prevention of ischemic heart disease, as was shown in many epidemiological as
      well as intervention studies. These fatty acids are essential and human organism
      is fully dependent on their dietary intake from chloroplast of green plants and
      fat of aquatic animals. Cardioprotective action of these acids results from their
      complex effect (antiarrhytmic, antithrombotic, antiinflammatory, hypolipidemic
      etc.). These acids can, with the exception of glucose homeostasis, favourably
      influence individual components of the metabolic syndrome. Beneficial effects of
      n-3 polyunsaturated fatty acids are supposed also in chronic inflammatory and
      autoimmune diseases, psychiatric-neurological diseases and malignant tumours. In
      the case of rheumatoid arthritis, antiinflammatory effects of polyunsaturated
      fatty acids were proven. In general, favourable effects of the optimal income of
      n-3 polyunsaturated fatty acids can be explained by the influencing of cellular
      metabolic functions, incorporation into membrane phospholipids, modulation of
      enzymes and signal molecules as well as by direct impact on gene expression.
      Polyunsaturated fatty acids of n-3 family have high therapeutic potential, which
      results from the combined action on different levels of cell functions. In some
      diseases, their effect is nearly pharmacological - prevention of the sudden death
      and fatal myocardial infarction, treatment of hyper- and dyslipoproteinemias,
      suppression of the inflammatory activity in rheumatoid arthritis. In another
      group of diseases, they have supporting effect (prevention of the arterial
      hypertension in metabolic syndrome) and, finally, in the last one (psychiatric
      neurological diseases and tumours), more data of defined clinical groups are
      necessary for final evaluation.

PMID- 15981981
TI  - [Insulin resistance, metabolic syndrome and cardiovascular diseases].
AB  - The article summarizes the nature and causes of the insulin resistance, its
      relation to the metabolic syndrome, and to the cardiovascular diseases. Insulin
      resistance can be defined as a set of abnormal clinical symptoms accompanied by
      lower tissue sensitivity to insulin. Metabolic syndrome, whose major components
      are impairments of glucose homeostase, obesity, dyslipidemia and arterial
      hypertension, represents an important risk factor for the development of diabetes
      mellitus type 2 and for the development of cardiovascular diseases. Possible
      factors, which can influence those relations, e.g., chronic inflammations,
      endothelial dysfunction and oxidation stress are discussed. The primary aims for
      the positive influencing the metabolic syndrome is the prevention of the
      development of diabetes mellitus type 2 and that of cardiovascular diseases. To
      approach those goals, the use of non-pharmacologic means (diet, appropriate
      physical activity) and pharmacologic (treatment of dyslipidemia, namely by
      statins and fibrates; management of hypertension, specifically by angiotensin
      converging enzyme inhibitors, by angiotensin-receptor blockers, by glitazoe
      administration and by antithrombotic treatment) can be recommended.

PMID- 15981982
TI  - [Value of duplex ultrasound examination of the proximal part of the common
      carotid artery].
AB  - A significant part of patients with carotid artery stenosis is operated on
      without preoperative angiography, to reduce the risks and cost of such
      examination. Duplex ultrasound often cannot reliable visualise the proximal parts
      of the aortic arch vessels. We evaluated the ability of duplex ultrasound to
      identify those types of lesions and ascertain their prevalence. We analysed
      retrospectively carotid duplex scans and carotid angiography in 448 carotid
      arteries. 17 significant proximal lesions (3.89%) were identified on the duplex
      scan and confirmed by angiography. Lesions of the proximal parts of the aortic
      arch vessels are rare and may be reliably detected by duplex ultrasound.

PMID- 15981983
TI  - [Cardiac abnormalities of lyme borreliosis].
AB  - The article summarizes basic characteristics of Lyme borreliosis, its incidence,
      epidemiology, pathogenesis and clinical image. Particular attention is given to
      the review of papers aimed at the cardiac abnormalities--the Lyme carditis.
      Though they are not very frequent, due to the variability of their clinical
      course and due to various forms, which are difficult to diagnose, they can
      represent a specific problem. Major part of the article is given to the authors'
      own experience with the dilated cardiomyopathy of the Borrelia origin and namely
      to the perspective study of the patients after the skin form of the disease
      erythema migrans, who were treated "lege artis" in the early phase of the disease
      with antibiotics. Authors were interested how many of those patients would
      develop later the cardiac abnormalities.

PMID- 15981984
TI  - [How endoscopy has changed in recent 60 years].
AB  - Sixty years ago only semi flexible instruments were used for the endoscopic
      examination of the gastrointestinal tract. They were developed by the German
      physician Rudolf Schindler together with George Wolf, the producer of medical
      instruments in 1932. They construct optical gastroscope with a system of lenses
      in the flexible distal end and with the rigid metallic proximal part. Those
      instruments were used in gastroscopy till the sixties when the era of
      fibroendoscopy with the use of glass fibre optic has started. In 1957 Basil
      Hirschowitz with his co-workers introduced a flexible gastroscope--a fibroscope.
      The next years brought improvement in the size of image, its brilliancy,
      possibility to control the distal end and a bioptic channels was added. Working
      length was elevated and since 1970 the instrument has been used as ezofago-gastro
      duodenoscope. At the end of millennium a new technology was developed-
      videoendoscopy. Experience with the prototype of videoendoscope was published in
      1984 (Sivak a Fleischer, Classen a Phillip). In the nineties of the previous
      century Paul Swain constructed the first prototype of wireless endoscopic
      capsule. A single chip camera with low electricity consumption was presented in
      2000. Endoscopy has developed in recent years considerably and its progress will
      definitely continue.

PMID- 15981985
TI  - [Protective mechanism of the gastric mucosa].
AB  - The gastric mucosa represents a masterpiece in the functional design. As the
      tissue lining the stomach, it secretes aggressive combination of digestive
      fluids, powerful enough to digest any tissue. Nonetheless, the gastric mucosa
      remains undamaged by the effect of its inherent protective mechanisms. The
      possibility of development of gastric erosions and ulcers remains vivid evidence
      that the gastric mucosa is not always resistant to injury.

PMID- 15981986
TI  - [Inflammatory bowel disease: knowledge advancement of the last sixty years].
AB  - Inflammatory bowel diseases, Crohn's disease and ulcerative colitis, were
      discovered in the twentieth century. The etiology and pathogenesis has been
      unsolved until now. At present, three etiological mutually involved factors can
      be considered. The most important turned out to be the genetics component, which
      can lead to the chronic inflammation of the bowel. The significant effects of
      infectious and environmental factors were proven in the pathogenesis of
      inflammatory bowel diseases. Despite many years elapsed, the "The binary
      pathogenesis theory of ulcerative colitis", postulated by Maratka in the sixties,
      can be still accepted.

PMID- 15981987
TI  - [Gluten enteropathy--occurrence, diagnosis, therapy].
AB  - Gluten enteropathy is a chronic all-life disease, characterized by typical
      inflammatory changes of the small bowel mucosa. It is the genetically determined
      autoimmune disease with permanent intolerance to gluten. Its clinical signs are
      very heterogeneous and also the severity of intestinal changes varies
      considerably. It frequently presents with atypical symptoms, as many as 80% of
      adult patients have no gastrointestinal troubles at all. The present estimated
      prevalence is 1:200 - 1:250. The diagnosis is based on criteria of the European
      Society of Paediatric Gastroenterology, Hepatology and Nutrition revised in 1990,
      above all on the detection of serum antibodies to endomysium and tissue
      transglutaminase. The five forms are distinguished: classic, subclinical, latent,
      potential and silent. Coeliac disease and dermatitis herpetiformis are considered
      to be two identical forms of the gluten enteropathy manifestations. Coeliac
      disease is frequently associated with other autoimmune diseases--diabetes
      mellitus, autoimmune thyreoiditis, hepatitis, IgA deficiency. Permanent gluten
      free diet is the cornerstone of the therapy; untreated gluten enteropathy is a
      serious illness, considered to be a significant precancerosis.

PMID- 15981988
TI  - [Hepatitis C viral infection at the beginning of twenty-first century].
AB  - The article reviews basic information on the epidemiology, origin, diagnostics
      and therapy of hepatitis C viral infection. Virus of the hepatitis C was
      identified in 1989. The most frequent transmission pathway till 1992 was the
      reception of blood derivatives, after that year, when transfusion centres started
      to use detection sets to prove anti-HCV antibodies, the incidence of post
      transfusion hepatitis C dropped almost to zero. The most common route of
      transmission at present is the intravenous toxicomany, and significant
      participation represents the medical care. The basic serological marker of HCV
      infection is the presence of anti-HCV antibodies. Those antibodies signify
      markers of the human contact with the virus; they need not automatically mean the
      encounter of infection. More often it is contrariwise--because the C viral
      hepatitis develops the chronic stadium up in 85%, the anti-HVC positivity
      signifies usually the active form of infection. To prove the active form of
      infection it is necessary to identify viral nucleic acids in the serum of the
      examined patient. The standard therapy of the chronic form of the C viral
      hepatitis is at present a combination of pegylated interpherons alpha and
      ribavirin. Such form of therapy can result the permanent elimination of the virus
      in about 60% of cases. In the C viral hepatitis neither the specific pre
      exposition nor post-exposition prophylaxis is available. The only prevention of
      the transmission of infection is the avoidance of any risk factor of
      transmission, namely in the medical care.

PMID- 15981989
TI  - [Cytoprotective effects of bilirubin].
AB  - Bilirubin, a major product of heme catabolism, belongs to compounds with
      pleiotropic biologic effects. For a long time bilirubin was considered as a
      metabolite dangerous for human health, neonatologists know well serious clinical
      complication of neonatal jaundice called bilirubin encephalopathy. Nevertheless,
      recent data has demonstrated that bilirubin exhibits potent antioxidant and even
      anti-inflammatory effects with substantial clinical impacts. The aim of the
      present study was to summarize present knowledge in this rapidly evolving field
      and suggest further possible clinical consequences.

PMID- 15981990
TI  - [Long-term pharmacological treatment of portal hypertension].
AB  - Portal hypertension is an unavoidable complication of liver cirrhosis, which
      usually limits the survival (bleeding from esophageal varices, ascites). Increase
      in portal pressure is not only due to mechanical obstruction of portal
      circulation, but there is also a dynamic component (endothelial dysfunction of
      hepatic microcirculation) and increased blood flow through the splanchnic
      circulation. For the long-term treatment of portal hypertension two groups of
      medicaments are available at present: non-selective betablockers
      (vasoconstriction in splanchnic bed) and nitrates (lowering of intrahepatic
      resistance). Long-term treatment is necessary in these situations: Primary
      prophylaxis of bleeding from esophageal varices (in patients, who never bled, but
      with "risk" varices)--non-selective betablockers; secondary prophylaxis (in
      patients after variceal bleeding)--non-selective betablockers (possibly with
      nitrates) or endoscopic treatment. It is clearly documented, that this treatment
      lowers the risk of the first or repeated bleeding from varices and hence lowers
      the mortality and morbidity due to this complication in patients with liver
      cirrhosis. Another serious complication of liver cirrhosis is the spontaneous
      bacterial peritonitis. All patients after that infection have to receive
      prophylactic treatment with antibiotics. This treatment should be long life, till
      the disappearance of ascites or till the liver transplantation.

PMID- 15981991
TI  - [Risk of malnutrition and the role of artificial nourishment].
AB  - Malnutrition represents a serious risk factor, which can bring about prolongation
      of the hospitalization, higher incidence of complications and higher mortality.
      Such relation is well documented in several epidemiologic studies. The treatment
      of malnutrition, though large progress has been reached in the treatment, forms
      and indications of enteral and parenteral artificial nourishment, is based first
      of all on the elimination of the original cause, i.e. in the treatment of the
      primary disease. Nevertheless the role of artificial nourishment is
      irreplaceable. It serves as a supportive therapy namely to overcome the period
      till the alimentation per os is restituted. In other cases, when the normal
      alimentation route is not possible to restitute in sufficient extent, the
      parenteral or enteral artificial nourishment remain the permanent necessity and
      the life rescuing treatment.

PMID- 15981992
TI  - Abstracts of the 3rd International Symposium on Intensive Care and Emergency
      Medicine for Latin America. Sao Paulo, Brazil. 22-25 June 2005.

PMID- 15981993
TI  - Protein dynamics in living cells.
AB  - A protein's structure is most often used to explain its function, but function
      also depends on dynamics. To date, protein dynamics have been studied only in
      vitro under dilute solution conditions where solute concentrations are typically
      less than 10 g/L, yet proteins function in a crowded environment where the solute
      concentration can exceed 400 g/L. Does the intracellular environment affect
      protein dynamics? The answer will help in assessing the biological significance
      of the NMR-derived dynamics data collected to date. We investigated fast protein
      dynamics inside living Escherichia coli by using in-cell NMR. The backbone
      dynamics of apocytochrome b5 were quantified using {1H}-15N nuclear Overhauser
      effect (nOe) measurements, which characterize motions on the pico- to nanosecond
      time scale. The overall trend of backbone dynamics remains the same in cells.
      Some of the nOe values differ, but most of the differences track the increased
      intracellular viscosity rather than a change in dynamics. Therefore, it appears
      that dilute solution steady-state {1H}-15N nOe measurements provide biologically
      relevant information about pico- to nanosecond backbone motion in proteins.

PMID- 15981994
TI  - Co-crystal structure and inhibition of factor Xa by PD0313052 identifies
      structurally stabilized active site residues of factor Xa and prothrombinase.
AB  - The enzyme complex prothrombinase plays a pivotal role in fibrin clot development
      through the production of thrombin, making this enzyme complex an attractive
      target for therapeutic regulation. This study both functionally and structurally
      characterizes a potent, highly selective, active site directed inhibitor of human
      factor Xa and prothrombinase, PD0313052, and identifies structurally conserved
      residues in factor Xa and prothrombinase. Analyses of the association and
      dissociation of PD0313052 with human factor Xa identified a reversible, slow
      onset mechanism of inhibition and a simple, single-step bimolecular association
      between factor Xa and PD0313052. This interaction was governed by association
      (k(on)) and dissociation (k(off)) rate constants of (1.0 +/- 0.1) x 10(7) M(-1)
      s(-1) and (1.9 +/- 0.5) x 10(-3) s(-1), respectively. The inhibition of human
      factor Xa by PD0313052 displayed significant tight-binding character described by
      a Ki* = 0.29 +/- 0.08 nM. Similar analyses of the inhibition of human
      prothrombinase by PD0313052 also identified a slow-onset mechanism with a Ki* =
      0.17 +/- 0.03 nM and a k(on) and k(off) of (0.7 +/- 0.1) x 10(7) M(-1) s(-1) and
      (1.7 +/- 0.8) x 10(-3) s(-1), respectively. Crystals of factor Xa and PD0313052
      demonstrated hydrogen bonding contacts within the S1-S4 pocket at residues
      Ser195, Asp189, Gly219, and Gly216, as well as interactions with aromatic
      residues within the S4 pocket. Overall, these data demonstrate that the
      inhibition of human factor Xa by PD0313052 occurs via a slow, tight-binding
      mechanism and indicate that active site residues of human factor Xa, including
      the catalytic Ser195, are effectively unaltered following assembly into
      prothrombinase.

PMID- 15981995
TI  - The effect of iodide and chloride on transthyretin structure and stability.
AB  - Transthyretin amyloid formation occurs through a process of tetramer
      destabilization and partial unfolding. Small molecules, including the natural
      ligand thyroxine, stabilize the tetrameric form of the protein, and serve as
      inhibitors of amyloid formation. Crucial for TTR's ligand-binding properties are
      its three halogen-binding sites situated at the hormone-binding channel. In this
      study, we have performed a structural characterization of the binding of two
      halides, iodide and chloride, to TTR. Chlorides are known to shield charge
      repulsions at the tetrameric interface of TTR, which improve tetramer stability
      of the protein. Our study shows that iodides, like chlorides, provide tetramer
      stabilization in a concentration-dependent manner and at concentrations
      approximately 15-fold below that of chlorides. To elucidate binding sites of the
      halides, we took advantage of the anomalous scattering of iodide and used the
      single-wavelength anomalous dispersion (SAD) method to solve the iodide-bound TTR
      structure at 1.8 A resolution. The structure of chloride-bound TTR was determined
      at 1.9 A resolution using difference Fourier techniques. The refined structures
      showed iodides and chlorides bound at two of the three halogen-binding sites
      located at the hydrophobic channel. These sites therefore also function as halide
      binding sites.

PMID- 15981996
TI  - A novel metabolic pathway of melatonin: oxidation by cytochrome C.
AB  - The indoleamine melatonin is ubiquitously distributed, and because of its small
      size and amphiphilic nature, it is able to reach easily all cellular
      compartments. The highest intracellular melatonin concentrations are found in the
      mitochondria, suggestive of local metabolism and/or direct participation in
      organelle function. In mitochondria cytochrome c (cyt c) could represent a
      melatonin target since it has the capability to oxidize organic molecules in the
      presence of H2O2, and mitochondria are the main site of H2O2 production in
      nonphagocytic cells. Therefore, we investigated oxidation of melatonin by cyt
      c/H2O2 couple as a potential pathway for its metabolism in the mitochondria. We
      found melatonin conversion into N(1)-acetyl-N(2)-formyl-5-methoxykynuramine via
      sequential steps that generate the intermediates 2-hydroxymelatonin and 2,3
      dihydroxymelatonin. We experimentally excluded mediation by a Fenton/Haber-Weiss
      type reaction and documented the dependence on oxoferryl heme for melatonin
      oxidation. Given the high mitochondrial concentrations of both melatonin and cyt
      c as well as the continuous generation of H2O2 during respiration, it is entirely
      possible that mitochondrial cyt c-mediated oxidation of melatonin may be a
      plausible pathway of its biotransformation in vivo.

PMID- 15981997
TI  - Mitochondrial and microsomal ferric b5 cytochromes exhibit divergent
      conformational plasticity in the context of a common fold.
AB  - Native-state hydrogen-deuterium exchange (HDX) monitored by NMR spectroscopy has
      been used to compare conformational plasticity in ferric rat liver outer
      mitochondrial membrane cytochrome b5 (rOM b5) and ferric bovine liver microsomal
      cytochrome b5 (bMc b5). Analysis of the data indicated that rOM b5 is the less
      conformationally flexible protein on the time scale probed by the HDX
      experiments. The data also suggest a likely contributor to the much higher
      kinetic barrier for the release of hemin from OM b5s in comparison to Mc b5s, a
      characteristic that may be to a large extent the source of their divergent
      functional properties. Specifically, the data indicate that conformational
      mobility within helices alpha4 and alpha5, which flank the loop harboring axial
      ligand His63, is considerably more restricted in rOM b5 than in bMc b5. The lower
      conformational flexibility of alpha4 and alpha5 in rOM b5 can reasonably be
      attributed to more extensive hydrophobic packing in that region of the protein,
      arising from two conserved side chain packing motifs in OM cytochrome b5s
      [Altuve, A., Wang, L., Benson, D. R., and Rivera, M. (2004) Biochem. Biophys.
      Res. Commun. 314, 602-609].

PMID- 15981998
TI  - Molecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from
      mutational and kinetic studies.
AB  - ADP-ribose pyrophosphatase (ADPRase), a member of the nudix protein family,
      catalyzes the hydrolysis of ADP-ribose to AMP and ribose 5'-phosphate. We have
      determined the crystal structure of ADPRase from Thermus thermophilus HB8
      (TtADPRase). We performed kinetic analysis of mutants of TtADPRase to elucidate
      the substrate recognition and the catalytic mechanism. Our results suggest that
      interactions responsible for the substrate recognition are located at the
      terminal moieties of the substrate. The adenine moiety is recognized by Ile-19
      and the main chain carbonyl group of Glu-29 and/or Gly-104. The terminal ribose
      moiety is recognized by the sum of some weak interactions with multiple residues
      that are close in space. Glu-82 and Glu-86, conserved in the nudix motif, were
      previously shown to be essential for catalysis. Mutation of these residues shows
      that the dependence of kcat on pH is almost the same as that of the wild-type
      enzyme. Results suggest that Glu-82 and Glu-86 are essential for catalysis but
      unlikely to act as a catalytic base. In the crystal structure, each acidic
      residue coordinates with a metal ion. Furthermore, a water molecule coordinates
      between these two metals. Our results suggest a two-metal ion mechanism for the
      catalysis of ADPRase in which a water molecule is activated to act as a
      nucleophile by the cations coordinated by Glu-82 and Glu-86. Arg-54, Glu-70, Arg
      81, and Glu-85 are predicted to support this nucleophilic attack on the alpha
      phosphate of the substrate. Interestingly, ADPRase displays differences in the
      substrate recognition and the catalytic mechanism from the models proposed for
      other nudix proteins. Our results highlight the diversity within the nudix
      protein family in terms of substrate recognition and catalysis.

PMID- 15981999
TI  - Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM
      beta-lactamase.
AB  - Beta-lactamase confers resistance to penicillin-like antibiotics by hydrolyzing
      their beta-lactam bond. To combat these enzymes, inhibitors covalently cross
      linking the hydrolytic Ser70 to Ser130 were introduced. In turn, mutant beta
      lactamases have emerged with decreased susceptibility to these mechanism-based
      inhibitors. Substituting Ser130 with glycine in the inhibitor-resistant TEM (IRT)
      mutant TEM-76 (S130G) prevents the irreversible cross-linking step. Since the
      completely conserved Ser130 is thought to transfer a proton important for
      catalysis, its substitution might be hypothesized to result in a nonfunctional
      enzyme; this is clearly not the case. To investigate how TEM-76 remains active,
      its structure was determined by X-ray crystallography to 1.40 A resolution. A new
      water molecule (Wat1023) is observed in the active site, with two configurations
      located 1.1 and 1.3 A from the missing Ser130 Ogamma; this water molecule likely
      replaces the Ser130 side-chain hydroxyl in substrate hydrolysis. Intriguingly,
      this same water molecule is seen in the IRT TEM-32 (M69I/M182T), where Ser130 has
      moved significantly. TEM-76 shares other structural similarities with various
      IRTs; like TEM-30 (R244S) and TEM-84 (N276D), the water molecule activating
      clavulanate for cross-linking (Wat1614) is disordered (in TEM-30 it is actually
      absent). As expected, TEM-76 has decreased kinetic activity, likely due to the
      replacement of the Ser130 side-chain hydroxyl with a water molecule. In contrast
      to the recently determined structure of the S130G mutant in the related SHV-1
      beta-lactamase, in TEM-76 the key hydrolytic water (Wat1561) is still present.
      The conservation of similar accommodations among IRT mutants suggests that
      resistance arises from common mechanisms, despite the disparate locations of the
      various substitutions.

PMID- 15982000
TI  - Crystal structures of potent thiol-based inhibitors bound to carboxypeptidase B.
AB  - This paper presents the crystal structure of porcine pancreatic carboxypeptidase
      B (pp-CpB) in complex with a variety of thiol-based inhibitors that were
      developed as antagonists of activated thrombin-activatable fibrinolysis inhibitor
      (TAFIa). Recent studies have indicated that a selective inhibitor of TAFIa could
      enhance the efficacy of existing thrombolytic agents for the treatment of acute
      myocardial infarction, one of the most prevalent forms of heart attacks.
      Unfortunately, activated TAFIa rapidly degrades in solution and cannot be used
      for crystallographic studies. In contrast, porcine pancreatic CpB is stable at
      room temperature and is available from commercial sources. Both pancreatic CpB
      and TAFIa are zinc-based exopeptidases, and the proteins share a 47% sequence
      identity. The homology improves considerably in the active site where nearly all
      of the residues are conserved. The inhibitors used in this study were designed to
      mimic a C-terminal arginine residue, one of the natural substrates of TAFIa. The
      X-ray structures show that the thiol group chelates the active site zinc, the
      carboxylic acid forms a salt bridge to Arg145, and the guanidine group forms two
      hydrogen bonds to Asp255. A meta-substituted phenyl was introduced into our
      inhibitors to reduce conformational freedom. This modification vastly improved
      the selectivity of compounds against other exopeptidases that cleave basic
      residues. Comparisons between structures indicate that selectivity derives from
      the interaction between the guanidine group in the inhibitors and an acidic
      active site residue. The location of this acidic residue is not conserved in the
      various carboxypeptidases.

PMID- 15982001
TI  - The procapsid binding domain of phi29 packaging RNA has a modular architecture
      and requires 2'-hydroxyl groups in packaging RNA interaction.
AB  - The phi29 packaging RNA (pRNA) is an essential component in the phi29
      bacteriophage DNA packaging motor, the strongest biomolecular motor known today.
      Utilizing Mg2+-dependent intermolecular base pairing interactions between two 4
      nucleotide loops within the pRNA procapsid binding domain, multiple copies of
      pRNA form a ring-shaped complex that is indispensable for packaging motor
      function. To understand pRNA structural organization and pRNA/pRNA interaction,
      studies were carried out on pRNA closed dimers, the simplest functional pRNA
      complex believed to be the building blocks for assembling the oligomeric ring.
      Tertiary folding and interactions in various pRNA mutants were evaluated based on
      measured closed dimer affinity that is directly linked to the proper positioning
      of the interacting loops. The data revealed that the procapsid binding domain
      contains two autonomous modules that are capable of interacting noncovalently to
      form a fully active species in pRNA/pRNA interaction. Deleting the 2'-hydroxyl
      groups in one of the interacting loops weakens the dimer affinity by 125-fold,
      suggesting potential tertiary interactions involving these 2'-hydroxyl groups.
      The results provide evidence that nonbase functional groups are involved in pRNA
      folding and interaction and lead to a simple model that describes the pRNA
      monomer configuration in terms of three arms spanning a hinge. The functional
      constructs developed here will aid biophysical and biochemical investigations of
      pRNA structure and function, as well as developments of pRNA-based technology for
      nanoscience and gene therapy.

PMID- 15982002
TI  - Ultrafast events in the folding of ferrocytochrome c.
AB  - Laser flash photolysis and stopped-flow methods have been used to study the
      dynamic events in the micro- to millisecond time bin in the refolding of horse
      ferrocytochrome c in the full range of guanidine hydrochloride concentration at
      pH 12.8 (+/-0.1), 22 degrees C. Under the absolute refolding condition, the
      earliest relaxation time of the unfolded protein chain is less than 1 micros. The
      chain then undergoes diffusive dynamics-mediated contraction and expansion, in
      which intrapolypeptide ligands make transient contacts with the heme iron, giving
      rise to two distinct kinetic phases of approximately 0.4 and approximately 3
      micros. Under moderate to absolute refolding conditions, the rates of these
      processes show little dependence on the denaturant concentration, indicating the
      absence of structural element in the incipient or the relaxed state. Chain
      expansion and contraction events continue until the polypeptide finds a stable
      and supportive transition state. The crossing of this transition barrier, which
      rate-limits the folding of alkaline ferrocytochrome c, is characterized by a
      stopped-flow measured time constant of approximately 3 ms in aqueous solvent.
      Observed kinetics thus implicate no submillisecond folding structure. The folding
      kinetics is effectively two state in which the unfolded polypeptide first relaxes
      to an unstructured chain and then crosses over a late rate-limiting barrier to
      achieve the native conformation. The experimentally observed rates as a function
      of guanidine hydrochloride concentration have been simulated by numerically
      calculated microscopic rates of a simple kinetic model that captures the
      essential features of folding.

PMID- 15982003
TI  - Electron spin-lattice relaxation of the S0 state of the oxygen-evolving complex
      in photosystem II and of dinuclear manganese model complexes.
AB  - The temperature dependence of the electron spin-lattice relaxation time T1 was
      measured for the S0 state of the oxygen-evolving complex (OEC) in photosystem II
      and for two dinuclear manganese model complexes by pulse EPR using the inversion
      recovery method. For [Mn(III)Mn(IV)(mu-O)2 bipy4]ClO4, the Raman relaxation
      process dominates at temperatures below 50 K. In contrast, Orbach type relaxation
      was found for [Mn(II)Mn(III)(mu-OH)(mu-piv)2(Me3 tacn)2](ClO4)2 between 4.3 and 9
      K. For the latter complex, an energy separation of 24.7-28.0 cm(-1) between the
      ground and the first excited electronic state was determined. In the S0 state of
      photosystem II, the T1 relaxation times were measured in the range of 4.3-6.5 K.
      A comparison with the relaxation data (rate and pre-exponential factor) of the
      two model complexes and of the S2 state of photosystem II indicates that the
      Orbach relaxation process is dominant for the S0 state and that its first excited
      state lies 21.7 +/- 0.4 cm(-1) above its ground state. The results are discussed
      with respect to the structure of the OEC in photosystem II.

PMID- 15982004
TI  - Inactivation of malonate semialdehyde decarboxylase by 3-halopropiolates:
      evidence for hydratase activity.
AB  - Malonate semialdehyde decarboxylase (MSAD) from Pseudomonas pavonaceae 170
      catalyzes the metal ion-independent decarboxylation of malonate semialdehyde and
      represents one of three known enzymatic activities in the tautomerase
      superfamily. The characterized members of this superfamily are structurally
      homologous proteins that share a beta-alpha-beta fold and a catalytic amino
      terminal proline. Sequence analysis, chemical labeling studies, site-directed
      mutagenesis, and NMR studies of MSAD identified Pro-1 as a key active site
      residue in which the amino group has a pKa value of 9.2. The available evidence
      suggests a mechanism involving polarization of the C-3 carbonyl group of malonate
      semialdehyde by the cationic Pro-1. A second critical active site residue, Arg
      75, could assist in the reaction by placing the substrate's carboxylate group in
      a favorable conformation for decarboxylation. In addition to the decarboxylase
      activity, MSAD has a hydratase activity as demonstrated by the MSAD-catalyzed
      conversion of 2-oxo-3-pentynoate to acetopyruvate. In view of this activity, MSAD
      was incubated with 3-bromo- and 3-chloropropiolate, and the subsequent reactions
      were characterized. Both compounds result in the irreversible inactivation of
      MSAD, making them the first identified inhibitors of MSAD. Inactivation by 3
      chloropropiolate occurs in a time- and concentration-dependent manner and is due
      to the covalent modification of Pro-1. The proposed mechanism for inactivation
      involves the initial hydration of the 3-halopropiolate followed by a
      rearrangement to an alkylating agent, either an acyl halide or a ketene. The
      results provide additional evidence for the hydratase activity of MSAD and
      further support for the hypothesis that MSAD and trans-3-chloroacrylic acid
      dehalogenase, the preceding enzyme in the trans-1,3-dichloropropene catabolic
      pathway, diverged from a common ancestor but conserved the necessary catalytic
      machinery for the conjugate addition of water.

PMID- 15982005
TI  - CTP:phosphocholine cytidylyltransferase binds anionic phospholipid vesicles in a
      cross-bridging mode.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) catalyzes the rate-limiting step in
      phosphatidylcholine (PC) synthesis, and its activity is regulated by reversible
      association with membranes, mediated by an amphipathic helical domain M. Here we
      describe a new feature of the CCTalpha isoform, vesicle tethering. We show, using
      dynamic light scattering and transmission electron microscopy, that dimers of
      CCTalpha can cross-bridge separate vesicles to promote vesicle aggregation. The
      vesicles contained either class I activators (anionic phospholipids) or the less
      potent class II activators, which favor nonlamellar phase formation. CCT
      increased the apparent hydrodynamic radius and polydispersity of anionic
      phospholipid vesicles even at low CCT concentrations corresponding to only one or
      two dimers per vesicle. Electron micrographs of negatively stained
      phosphatidylglycerol (PG) vesicles confirmed CCT-mediated vesicle aggregation.
      CCT conjugated to colloidal gold accumulated on the vesicle surfaces and in areas
      of vesicle-vesicle contact. PG vesicle aggregation required both the membrane
      binding domain and the intact CCT dimer, suggesting binding of CCT to apposed
      membranes via the two M domains situated on opposite sides of the dimerization
      domain. In contrast to the effects on anionic phospholipid vesicles, CCT did not
      induce aggregation of PC vesicles containing the class II lipids, oleic acid,
      diacylglycerol, or phosphatidylethanolamine. The different behavior of the two
      lipid classes reflected differences in measured binding affinity, with only
      strongly binding phospholipid vesicles being susceptible to CCT-induced
      aggregation. Our findings suggest a new model for CCTalpha domain organization
      and membrane interaction, and a potential involvement of the enzyme in cellular
      events that implicate close apposition of membranes.

PMID- 15982007
TI  - Vesicular polydiacetylene sensor for colorimetric signaling of bacterial pore
      forming toxin.
AB  - A vesicle-based polydiacetylene biosensor for colorimetric detection of bacterial
      pore-forming toxin streptolysin O (SLO) is reported. The sensor was constructed
      with three lipid constituents: glycine-terminated diacetylene lipid Gly-PCDA,
      cell membrane-mimicking component PC-DIYNE, and cholesterol (CHO), which serves
      as the bait molecule. UV irradiation led to photopolymerization of the
      diacetylene lipids that gave the material a blue appearance. Incubation of the
      vesicles with SLO from Streptococcus pyrogenes turned the vesicle solution red,
      and the color change was found to be correlated to SLO concentration. The optimal
      sensing performance was found with vesicles consisting of 71% Gly-PCDA, 25% CHO,
      and 4% PC-DIYNE, and a correlation relationship was obtained for 20 HU to 500
      HU/mL, or 100 pM to 6.3 nM of SLO toxin. Transmission electron microscopy and
      dynamic light scattering was used for further characterization of the vesicular
      assemblies. Transmembrane pores (holes) with diameter around 30 nm were observed
      on the vesicle membranes, in particular on the peripheral of the membrane
      structures, suggesting pore formation by SLO toxin provides the driving force for
      the color change of the functional vesicles.

PMID- 15982008
TI  - Improved pattern transfer in nanoimprint lithography at 30 nm half-pitch by
      substrate-surface functionalization.
AB  - Resist detachment from the substrate during mold-substrate separation is one of
      the key challenges for nanoimprint lithography as the pitch of features
      decreases. We analyzed the problem by considering the surface and interfacial
      free energies of the initial state and the possible final states of the mold
      polymer-substrate system and designed the chemistry of the system to provide the
      desired final state. We dramatically improved the resist adhesion to the
      substrate by assembling a monolayer of surface linker molecules on the substrate
      surface. A 37 nanowire pattern at 30 nm half-pitch was imprinted onto the surface
      modified substrate.

PMID- 15982010
TI  - Phase separation in class II organically modified silicate films as probed by
      phase-imaging atomic force microscopy.
AB  - Phase imaging tapping mode atomic force microscopy has been used to examine the
      presence and extent of phase separation in organically modified silicate films. A
      total of seven films were prepared using two different synthetic routes
      (cohydrolysis/condensation and separate hydrolysis/condensation) with three
      different organoalkoxysilanes and tetraethoxysilane. Films made from separately
      hydrolyzed sols were rougher and had larger phase separated domains compared to
      films prepared from cohydrolyzed sols. Likewise, films prepared from sols
      containing organoalkoxysilanes with nonpolar bulky substituents, such as ethyl
      and isobutyl, were significantly rougher and more phase separated relative to
      those prepared from a more miscible nitrile alkoxysilane.

PMID- 15982009
TI  - Small-angle neutron scattering from mixtures of sodium dodecyl sulfate and a
      cationic, bolaform surfactant containing azobenzene.
AB  - This paper reports on the microstructures formed in aqueous solutions containing
      mixtures of sodium dodecyl sulfate (SDS) and a photosensitive, bolaform
      surfactant, bis(trimethylammoniumhexyloxy)azobenzene dibromide (BTHA). By using
      quasi-elastic light scattering and small-angle neutron scattering, we determined
      that aqueous solutions containing SDS and the trans isomer of BTHA (0.1 wt %
      total surfactant, 15 mol % BTHA, 85 mol % SDS) form vesicles with average
      hydrodynamic diameters of 1350 +/- 50 angstroms and bilayer thicknesses of 35 +/-
      2 angstroms. The measured bilayer thickness is consistent with a model of the
      vesicle bilayer in which the trans isomer of BTHA spans the bilayer. Upon
      illumination with UV light, the BTHA underwent photoisomerization to produce a
      cis-rich photostationary state (80% cis isomer). We measured this
      photoisomerization to drive the reorganization of vesicles into cylindrical
      aggregates with cross-sectional radii of 19 +/- 3 angstroms and average
      hydrodynamic diameters of 240 +/- 50 angstroms. Equilibration of the cis-rich
      solution in the dark at 25 degrees C for 12 h or illumination of the solution
      with visible light leads to the recovery of the trans-rich photostationary state
      of the solution and the reformation of vesicles, thus demonstrating the potential
      utility of this system as the basis of a tunable fluid.

PMID- 15982011
TI  - Structural characterization of self-assembled monolayers of neoglycoconjugates
      using atomic force microscopy.
AB  - Thiolated self-assembled monolayers of carbohydrates may serve as useful
      polyvalent tools to mimic the organized presentation of such molecules at the
      cell surface. SAMs presenting the disaccharide maltose as a neoglycoconjugate
      were produced, and the structure was studied by high resolution atomic force
      microscopy. The molecules form highly ordered structures on a gold (111) surface,
      with lattice parameters determined by the linker moiety rather than the
      headgroup.

PMID- 15982012
TI  - Supercritical carbon dioxide processing of fluorinated surfactant templated
      mesoporous silica thin films.
AB  - The effect of processing mesoporous silica thin films with supercritical CO2
      immediately after casting is investigated, with a goal of using the penetration
      of CO2 molecules in the tails of fluorinated surfactant templates to tailor the
      final pore size. Well-ordered films with two-dimensional hexagonal close-packed
      pore structure are synthesized using a cationic fluorinated surfactant, 1
      (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)pyridinium chloride,
      as a templating agent. Hexagonal mesopore structures are obtained for both
      unprocessed films and after processing the cast films in CO2 at constant pressure
      (69-172 bar) and temperature (25-45 degrees C) for 72 h, followed by traditional
      heat treatment steps. X-ray diffraction and transmission electron microscopy
      analysis reveal significant increases in pore size for all CO2-treated thin films
      (final pore diameter up to 4.22 +/- 0.14 nm) relative to the unprocessed sample
      (final pore diameter of 2.21 +/- 0.20 nm) before surfactant extraction. Similar
      pore sizes are obtained with liquid and supercritical fluid treatments over the
      range of conditions tested. These results demonstrate that combining the tunable
      solvent strength of compressed and supercritical CO2 with the "CO2-philic" nature
      of fluorinated tails allows one to use CO2 processing to control the pore size in
      ordered mesoporous silica films.

PMID- 15982013
TI  - Formation of titania nanofibers: a direct sol-gel route in supercritical CO2.
AB  - In this letter, we present a new method to synthesize titania nanofibers with
      nanocrystallites via a sol-gel route in supercritical CO2. The nanofibers were
      formed by the esterification and condensation of titanium alkoxides using acetic
      acid as the polymerization agent in supercritical CO2 from 40 to 70 degrees C and
      2500 to 8000 psia. The TiO2 nanofiber morphology was characterized by means of
      SEM and HRTEM, which indicated that the diameters ranged from 9 to 100 nm. N2
      physisorption, and powder XRD showed that the nanofibers exhibited relatively
      high surface areas up to 400 m2/g and anatase and/or rutile nanocrystallites were
      formed after calcination.

PMID- 15982014
TI  - Novel method for the preparation of anionic surfactant-selective electrodes.
AB  - A simple one-step synthesis is described for the functionalization of poly(vinyl
      chloride) used for the preparation of anionic surfactant-selective membrane
      electrodes. The method is based on the nucleophilic substitution of a fraction of
      the chlorine atoms bound to the poly(vinyl chloride) backbone by trimethylamine.
      The prepared slightly charged polymer gave rise to high-quality surfactant
      selective electrode membranes, which had a Nernstian response, short response
      time, and appropriate stability.

PMID- 15982015
TI  - Effect of density fluctuating supercritical carbon dioxide on polymer interfaces.
AB  - We investigated an effect of CO2 sorption on the compatibility of immiscible
      polystyrene (PS) and polybutadiene (PB) bilayers by using in situ neutron
      reflectivity. By labeling either polymer with deuterium, we found that the excess
      CO2 molecules were adsorbed to both top PS and bottom PB layers when the bilayers
      were exposed to CO2 at the narrow T and P regime near the critical point of pure
      CO2. Furthermore, we clarified that this excess sorption of CO2 molecules
      increased the interfacial width between the layers up to 100 angstroms even near
      room temperature, while the interfacial width without CO2 exposure has been
      reported to be at most 40 A even at the highest temperature (T congruent with 175
      degrees C).

PMID- 15982016
TI  - Selective synthesis of single-crystalline selenium nanobelts and nanowires in
      micellar solutions of nonionic surfactants.
AB  - Single-crystalline nanobelts and nanowires of trigonal selenium (t-Se) have been
      selectively synthesized in micellar solutions of nonionic surfactants. In
      particular, t-Se nanobelts about 30 nm in thickness were obtained in micellar
      solutions of poly(oxyethylene(20)) octadecyl ether (C18EO20), whereas t-Se
      nanowires were obtained in micellar solutions of poly(oxyethylene(10)) dodecyl
      ether (C12EO10). The obtained t-Se nanobelts exhibit a low-energy absorption peak
      that is considerably red shifted from that for t-Se nanowires, which has been
      presumably attributed to the lower degree of crystal perfection for the t-Se
      nanobelts with rectangular cross sections.

PMID- 15982017
TI  - Polysaccharide-induced order-to-order transitions in lyotropic liquid crystals.
AB  - We report on the order-to-order transitions of lyotropic liquid crystals formed
      by self-assembled monogylcerides and water in the presence of polysaccharides of
      various molecular weights. The phase diagram of monoglyceride-water
      polysaccharide systems, their morphology, and the topology of liquid crystalline
      structures were determined by combining optical cross-polarization, oscillatory
      shear rheometry, and small-angle X-ray scattering. The presence of hydrophilic
      mono-, oligo-, and polysaccharides in the water domains of liquid crystalline
      phases resulted in a general decrease of the cubic-to-hexagonal transition
      temperature. Provided that the sugar could fit within the water channels, the
      decrease was observed to be dependent on the polysaccharide concentration but
      independent of its molecular weight. For isotropic bicontinuous cubic phases,
      monomeric sugars such as glucose were reported to shrink the lattice parameter of
      the structure without inducing phase transitions. However, when a polymeric form
      of glucose was used, such as dextran, transitions from the gyroidal Ia3d cubic
      phase to double diamond Pn3m cubic phases were observed at well-defined molecular
      weights of polysaccharide. These results were interpreted in terms of size
      exclusions of polymer sugars by the water domains of the liquid crystal phases as
      well as the different topologies of water channels. Molecular dynamics
      simulations of polysaccharides in the water environment were performed to support
      these findings.

PMID- 15982018
TI  - Micelles and gels of mixed triblock copoly(oxyalkylene)s in aqueous solution.
AB  - The micellization in dilute aqueous solution of a 50/50 wt% mixture of two
      triblock copolymers, E45B14E45 and E62P39E62, and the gelation of concentrated
      micellar solutions have been investigated over a range of temperatures. Here E,
      B, and P denote oxyethylene, oxubutylene, and oxypropylene chain units.
      Comparison is made with aqueous solutions of the individual copolymers. The
      results of light scattering measurements are consistent with effectively separate
      micellization of the two copolymers in the mixture. Hard gel formed when the
      extent of micellization was high for both copolymers. Because of the relatively
      high critical micellization temperatures of copolymer E62P39E62, the low
      temperature boundary of the hard gel was high for this copolymer and for the
      mixture. The minimum concentration for hard-gel formation was higher for the
      mixture than for either of the individual copolymers, as would be expected for
      packing of two distributions of micelles of different average size.

PMID- 15982019
TI  - Cosolvent effects on the stability of catanionic vesicles formed from ion-pair
      amphiphiles.
AB  - Four ion-pair amphiphiles (IPAs), derived from the pairing of
      alkyltrimethylammonium chlorides and sodium alkyl sulfates, were used to form
      catanionic vesicles in water upon the mechanical dispersion method. For the first
      time in the literature, short-chained alcohols (methanol, ethanol, 1-propanol,
      and 1-butanol) were added as cosolvents at a variety of concentrations and
      systematically studied for their effects on the stability of the ensuing
      vesicles. Dynamic light scattering measurements indicated that vesicles formed
      from one of the IPAs (i.e., dodecyltrimethylammonium dodecyl sulfate) could be
      efficiently and successfully stabilized by the addition of appropriate amounts of
      1-propanol and 1-butanol. Maximum lifetimes of more than 1 year and 132 days for
      stable vesicles in 5% 1-butanol and 15% 1-propanol solutions, respectively, were
      observed, and this demonstrates that a novel method for the stabilization of
      catanionic vesicles formed from IPAs becomes available by means of cosolvent
      addition. Furthermore, the stability of catanionic vesicles was found to be
      strongly dependent on cosolvent concentration. In general, the vesicle stability
      increased with increasing the cosolvent concentration, reached a maximum at a
      specific concentration, and thereafter decreased with further increasing the
      concentration. The vesicles finally disintegrated into constituent molecules in
      solutions of high cosolvent concentrations. An explanation of cosolvent effects
      based on the medium dielectric constant was proposed.

PMID- 15982020
TI  - Cosolvent effects on the spontaneous formation of vesicles from 1:1 anionic and
      cationic surfactant mixtures.
AB  - This paper aims to provide a practical catanionic vesicle-boosting method by
      means of cosolvent addition in water and to propose a theoretical explanation
      which can delineate the general trend of cosolvent effects and elucidate the
      possible role of cosolvent in the formation of catanionic vesicles. Effects of
      four homologous cosolvents (methanol, ethanol, 1-propanol, and 1-butanol) on the
      spontaneous formation of vesicles from eight 1:1 anionic-cationic mixed
      surfactant systems, sodium alkyl sulfates-alkyltrimethylammonium bromides
      (C(n)SO4Na-C(m)N(CH3)3Br; n = 12, 14; m = 8, 10, 12, 14), at a total surfactant
      concentration of 10 mM were systematically studied. The experimental results
      revealed that varied changes in vesicle formability of different mixed surfactant
      systems may result from various kinds and amounts of cosolvent. Four types of
      cosolvent effects, however, can be classified. Among them, cosolvent effects type
      2 and type 3 would serve the purpose and were exemplified by C12SO4Na
      C10N(CH3)3Br, C14SO4Na-C10N(CH3)3Br, and C12SO4Na-C12N(CH3)3Br mixed surfactants.
      Furthermore, the effectiveness of vesicle boosting increases in the order 1
      butanol > 1-propanol > ethanol > methanol. An explanation of cosolvent effects
      based on the medium dielectric constant was then proposed.

PMID- 15982021
TI  - Droplet deformation in dc electric fields: the extended leaky dielectric model.
AB  - The leaky dielectric model (LDM) was extended to large droplet distortions in dc
      electric fields. The resulting extended LDM (ELDM) reduces to the LDM for small
      droplet aspect ratios and to the pure dielectric model when the ratio of droplet
      and matrix conductivities equals the inverse ratio of their permittivities. The
      ELDM distinguishes between two types of phenomena possible at high electric
      fields: continuous deformation and hysteresis. For droplets deforming parallel to
      the electric field, the relationship that distinguishes between the two phenomena
      is a function of the droplet and matrix conductivities and viscosities but not of
      their permittivities. For droplets deforming perpendicular to the electric field,
      the relationship is a function of the droplet permittivities and conductivities
      but depends only slightly on the ratio of their viscosities. Some of the
      predictions of the LDM and the ELDM were compared with our own data and with data
      from the literature. For the systems that deformed parallel to the field
      direction, the ELDM not only predicted the data qualitatively but also predicted
      the data quantitatively when the experimental errors in its input parameters were
      taken into account, whereas the older LDM did not even predict the qualitative
      trend of the data. For the systems that deformed perpendicular to the field
      direction, however, the ELDM predicted the observed the aspect ratios in only one
      out of the four systems examined. In the other three systems, the LDM appeared to
      give reasonable predictions when either the ratio of the matrix/droplet
      viscosities was relatively small or the value of total charge relaxation time was
      relatively large. Thus, the applicability of the ELDM, as presently formulated,
      appears to be limited in the case of deformations perpendicular to the electric
      field.

PMID- 15982022
TI  - From decanoate micelles to decanoic acid/dodecylbenzenesulfonate vesicles.
AB  - Different aspects of mixtures of decanoic acid and sodium decanoate were
      investigated in aqueous solution up to a total concentration of 300 mM. Depending
      on the ratio of ionized to nonionized decanoic acid, micelles or vesicles form
      above the critical concentrations of micelle (cmc) or the critical concentration
      for vesicle formation (cvc). The micelles and the vesicles are always present
      together with nonmicellized or nonvesiculized decanoate. The latter was
      determined for different total concentrations. On the basis of titration curves,
      by application of the Gibbs phase rule, and on the basis of differential scanning
      calorimetry measurements and an electron microscopy analysis, the pH region
      within which vesicles exist was identified (pH 6.8-7.8). At pH 7.0, the
      concentration of nonvesiculized decanoate is approximately 20 mM. Decanoic
      acid/decanoate vesicles can be sized down by the extrusion technique to form
      stable and mainly unilamellar vesicles with a mean diameter of less than 100 nm.
      By coaddition of an equimolar amount of sodium dodecylbenzenesulfonate (SDBS) to
      decanoic acid, vesicles also formed below pH 6.8. These mixed vesicles were
      investigated as potential templates for the peroxidase-catalyzed polymerization
      of aniline at pH 4.3. Furthermore, decanaote micelles (at pH 11.0) were applied
      as reaction modifiers for the simultaneous competitive alkaline hydrolysis of p
      nitrophenylacetate and fluorescein diacetate. While the rate of hydrolysis of
      fluorescein diacetate is slowed considerably in the presence of the micelles in
      comparison with the micelle-free system, the rate of hydrolysis of p
      nitrophenylacetate remains almost unaffected.

PMID- 15982023
TI  - Electrokinetics of diffuse soft interfaces. III. Interpretation of data on the
      polyacrylamide/water interface.
AB  - Streaming potential measurements were carried out on a family of polyacrylamide
      co-sodium acrylate gels cross-linked with N,N'-methylenebisacrylamide in a
      homemade electrokinetic cell. Measurements of the ionic conductivity within thin
      films of these gels allowed the equilibrium Donnan potential difference between
      the bulk gel and the bulk electrolyte environments to be estimated at various
      ionic strengths. The resulting Donnan potential data were combined with the
      directly measurable streaming potential data and used to evaluate the diffuse
      soft interface model of electrokinetics (Langmuir 2004, 20, 10324). The model
      introduces the concept of a gradual decay of polymer density and fixed charge
      density within a narrow inter-phase at the gel/solution interface. The nature of
      the decay at the interface has a dramatic effect on the magnitude of the
      streaming potential as predicted by the diffuse soft interface model. In this
      investigation, the gradual decay of polymer density within the inter-phase is
      described with a hyperbolic tangent function. For the gels mentioned, the
      characteristic length scale of the decay, alpha, as calculated from the fit to
      the model, increases significantly with decreasing ionic strength, suggesting an
      osmotically driven swelling of the loosely cross-linked polymer chains at the
      interface. The experimental data and the results of the fitting are discussed in
      terms of the physical picture of the interface and compared to fitting results
      for a model which assumes a simple step function at the gel-solution interface.

PMID- 15982024
TI  - Influence of droplet characteristics on the formation of oil-in-water emulsions
      stabilized by surfactant-chitosan layers.
AB  - The objective of this study was to establish the optimum conditions for preparing
      stable oil-in-water emulsions containing droplets surrounded by surfactant
      chitosan layers. A primary emulsion containing small droplets (d32 approximately
      = 0.3 microm) was prepared by homogenizing 20 wt% corn oil with 80 wt% emulsifier
      solution (20 mM SDS, 100 mM acetate buffer, pH 3) using a high-pressure valve
      homogenizer. The primary emulsion was diluted with chitosan solutions to produce
      secondary emulsions with a range of oil and chitosan concentrations (0.5-10 wt%
      corn oil, 0-1 wt% chitosan, pH 3). The secondary emulsions were sonicated to help
      disrupt any droplet aggregates formed during the mixing process. The electrical
      charge, particle size, and amount of free chitosan in the emulsions were then
      measured. The droplet charge changed from negative to positive as the amount of
      chitosan in the emulsions was increased, reaching a relatively constant value
      (approximately +50 mV) above a critical chitosan concentration (C(Sat)), which
      indicated that saturation of the droplet surfaces with chitosan occurred.
      Extremely large droplet aggregates were formed at chitosan concentrations below
      C(Sat), but stable emulsions could be formed above C(Sat) provided the droplet
      concentration was not high enough for depletion flocculation to occur.
      Interestingly, we found that stable multilayer emulsions could also be formed by
      mixing chitosan with an emulsion stabilized by a nonionic surfactant (Tween 20)
      due to the fact the initial droplets had some negative charge. The information
      obtained from this study is useful for preparing emulsions stabilized by
      multilayer interfacial layers.

PMID- 15982025
TI  - Cholic acid-derived facial amphiphiles with different ionic characteristics.
AB  - A cholate derivative with three epoxide groups was synthesized from cholic acid
      by allylation followed by epoxidation. Ring opening of the epoxides by various
      nucleophiles yielded facial amphiphiles with anionic, cationic, or nonionic
      functional groups. The critical micelle concentrations of these amphiphiles
      largely depend on the number of charged groups on the molecule. A facial
      amphiphile with pH-tunable micellization was prepared. Its aggregation behavior
      changes abruptly at pH = 7.6-6.6 as a result of protonation of its amino groups.

PMID- 15982026
TI  - Rheological behavior and structural interpretation of waxy crude oil gels.
AB  - A waxy crude oil which gels below a threshold temperature has been investigated
      under static and dynamic conditions, using a combination of rheological methods,
      optical microscopy, and DSC. Particular attention is given in this work to the
      influence of the mechanical history on gel strength and to describing the time
      dependent rheological behavior. The gels display a strong dependence of the yield
      stress and moduli on the shear history, cooling rate, and stress loading rate. Of
      particular interest is the partial recovery of the gel structure after
      application of small stress or strain (much smaller than the critical values
      needed for flow onset) during cooling, which can be used to reduce the ultimate
      strength of the crude oil gel formed below the pour point. A second focus of this
      study is to further develop the physical interpretation of the mechanism by which
      wax crystallization produces gelation. Gelation of the waxy crude oil studied is
      suggested to be the result of the association between wax crystals, which
      produces an extended network structure, and it is shown that the system displays
      features common to attractive colloidal gels, for one of which, fumed silica
      (Aerosil 200) in paraffin oil, rheological data are reported. The colloidal gel
      model provides a simple and economical basis for explaining the response of the
      gelled oil to various mechanical perturbations and constitutes a fruitful basis
      from which to develop technologies for controlling the gelation phenomenon, as
      suggested by the rheological results reported.

PMID- 15982027
TI  - Interaction of dipicolinatodioxovanadium(V) with polyatomic cations and surfaces
      in reverse micelles.
AB  - In confined media such as reverse micelles, molecular probes frequently reside at
      and interact strongly with the interface. If the interface is charged, it is
      often difficult to separate effects arising from interactions with the charged
      species from the effect of the interfacial environment. With reverse micelles as
      a model system, the work reported here explores the interaction of the charged
      surfactant headgroups at a self-assembled interface with the
      dipicolinatodioxovanadium(V) coordination complex. The vanadium complex studied
      in these experiments serves as an excellent probe to investigate how charged
      metal complexes interact with lipid interfaces. For comparison, measurements were
      also carried out probing the interaction of the vanadium complex with a model
      cationic headgroup, tetramethylammonium bromide. The impact of the environment is
      gauged by changes in the 51V chemical shift, longitudinal relaxation times, and
      1H NMR pulsed field gradient measurements. These measurements suggest that while
      interface component parts, as modeled by the dispersed systems, interact with the
      vanadium complex, the interfacial environment perturbs the complex substantially
      more strongly than the sum of the components alone. Coulomb attraction dominates
      the interaction in all systems probed and surprisingly orients the hydrophobic
      portion into the bulk water.

PMID- 15982028
TI  - Influence of anionic surfactants on the electric percolation of
      AOT/isooctane/water microemulsions.
AB  - A study was carried out concerning the influence of sodium alkyl sulfonates on
      the electric percolation of AOT/isooctane/water microemulsions ([AOT] = 0.5 M and
      W = [H2O]/[AOT] = 22.2). An important effect was observed with regard to the
      percolation temperature caused by the addition of small quantities of alkyl
      sulfonates (rho = [alkyl sulfonate]/[AOT] = 0.01). The short chain alkyl
      sulfonates (C3-C5) cause an increase in the percolation temperature, which in
      turn is reduced as we increase the chain length of the additive until we obtain a
      percolation temperature which is lower than that which is observed in the absence
      of an additive (C6-C8). For hydrocarbon chains of a greater length we can observe
      a new increase in the percolation temperature (C10-C18). This behavior has been
      explained as a consequence of (i) the incorporation of the additives at the
      interphase of the microemulsion and (ii) the geometric parameters of the
      different surfactants added to the microemulsion.

PMID- 15982029
TI  - Relating foam lamella stability and surface dilational rheology.
AB  - The surface dilational elasticity module E of a soluble cationic surfactant at
      the air-water interface is measured in a frequency range of 1-500 Hz. The data
      are then correlated with the lifetime of a foam lamella formed with the same
      surfactant solution. The surface rheological measurement have been performed with
      an improved design of the oscillating bubble technique that measures precisely
      the real and imaginary part of the complex dilational module E. The imaginary
      part captures a dissipative process which is interpreted as an intrinsic surface
      dilational viscosity kappa. The cationic surfactant 1-dodecyl-4
      dimethylaminopyridinium bromide shows a transition between a surface elastic to a
      viscoelastic behavior with an increase of the bulk concentration. The transition
      corresponds to a striking increase in the lifetime of the foam lamella. The
      lamella lifetime of the viscoelastic system exceeds the one of an elastic system
      by 2 orders of magnitude while the absolute value of the E module remains
      comparable. The results suggest that surface dilational viscosity kappa is
      crucial for the ability of a surfactant system to form a stable foam. A simple
      picture that explains this observation is discussed.

PMID- 15982030
TI  - Spontaneous spreading of nematic liquid crystals.
AB  - The spontaneous spreading of macroscopic drops of nematic liquid crystals on
      hydrophilic substrates has been investigated by interferometric techniques. There
      is a complex interplay between the elastic energy, due to antagonist anchoring at
      the interfaces, and the radial flow in the spreading drop. A relevant parameter
      appears to be the relative humidity of the atmosphere, because it controls the
      amount of water molecules adsorbed on the substrate and, therefore, the strength
      of anchoring defects. The spreading laws differ from the ones of simple wetting
      liquids, and contact line instabilities coupled to short- (anchoring) or large
      scale (disclinations) defects of the nematic film are observed.

PMID- 15982031
TI  - Iron oxide pillared graphite.
AB  - We show that alpha-Fe2O3- and Fe3O4-pillared graphites can be prepared by
      pillaring graphite oxide with trinuclear iron acetato complex ion and calcining
      it in air and in vacuo, respectively. A pillared graphite structure is confirmed
      by transmission electron microscopy observations. The adsorption isotherms of
      water indicate that the mesopores of Fe3O4-pillared graphite constitute a
      hydrophobic nanospace.

PMID- 15982032
TI  - Enthalpy and entropy effects in hydrogen adsorption on carbon nanotubes.
AB  - Interaction energies and entropies associated with hydrogen adsorption on the
      inner and outer surfaces of zigzag single-wall carbon nanotubes (SWCNT) of
      various diameters are analyzed by means of molecular mechanics, density
      functional theory, and ab initio calculations. For a single molecule the
      strongest interaction, which is 3.5 greater than that with the planar graphite
      sheet, is found inside a (8,0) nanotube. Adsorption on the outer surfaces is
      weaker than that on graphite. Due to the steric considerations, both processes
      are accompanied by an extremely strong decline in entropy. Absence of specific
      adsorption sites and weak attractive interaction between hydrogen molecules
      within carbon nanotubes results in their close packing at low temperatures. Using
      the calculated geometric and thermodynamic parameters in Langmuir isotherms we
      predict the adsorption capacity of SWCNTs at room temperature to be smaller than
      1 wt % even at 100 bar.

PMID- 15982033
TI  - Temperature-dependent formation of octadecylsiloxane self-assembled monolayers on
      mica as studied by atomic force microscopy.
AB  - We have investigated the growth of octadecylsiloxane (ODS) self-assembled
      monolayers on mica. Freshly cleaved muscovite mica and octadecyltrichlorosilane
      (OTS) dissolved in toluene (c = 1.0 mmol/L) have been used as substrate and
      precursor, respectively. The water content of the adsorption solution was between
      14.6 and 16.6 mmol/L. Adsorption experiments were carried out in a temperature
      range between 5 and 45 degrees C, and the obtained submonolayer ODS films were
      characterized with atomic force microscopy (AFM). Besides the morphology of the
      films, also information on the surface coverage has been obtained by quantitative
      evaluation of the AFM images. Depending on the temperature, evidence for both
      ordered and disordered expanded ODS phases has been found. The pronounced maximum
      in surface coverage--in contrast to adsorption on silicon substrates--at a
      temperature of about 27 degrees C and the different morphology of the
      submonolayer films as compared to silicon substrates could be explained in terms
      of a deposition, diffusion, and aggregation (DDA) model.

PMID- 15982034
TI  - Phospholipid solubility determined by equilibrium distribution between surface
      and bulk phases.
AB  - A general strategy is proposed for determining the very low aqueous solubility
      limits of bilayer-forming phospholipids. The strategy exploits the inherent
      surface activity of phospholipids and has been termed EDSB, which stands for
      Equilibrium Distribution between Surface and Bulk phases. In this report, EDSB
      has been used to determine the critical bilayer concentration of
      dilauroylphosphatidylycholine (DLPC), a short-chain bilayer-forming phospholipid.
      At room temperature in neutral pH buffer, CBC(DLPC) = 2.5 x 10(-)(8) M. Using a
      mole fraction concentration scale, this corresponds to a standard-state free
      energy change of -12.8 kcal/mol for DLPC bilayer membrane formation.

PMID- 15982035
TI  - Characterization of maleic acid/anhydride copolymer films by low-rate dynamic
      liquid-fluid contact angle measurements using axisymmetric drop shape analysis.
AB  - Thin films of alternating maleic acid/anhydride copolymers (poly(octadecene-alt
      maleic acid/anhydride), POMA; poly(propene-alt-maleic acid/anhydride), PPMA;
      poly(styrene-alt-maleic acid/anhydride), PSMA) were studied to unravel the
      influence of the comonomer characteristics in the backbone on the surface
      energetic properties of the copolymer films in the dry state and in contact with
      aqueous solutions. Water contact angle measurements revealed a graduation of the
      wettability of the dry hydrolyzed and annealed copolymer films that was dependent
      on the comonomer unit. It ranged from moderately hydrophilic (PPMA, annealed
      gamma(sv) = 39.9 mJ/m2) to very hydrophobic (POMA, annealed, gamma(sv) = 18.4
      mJ/m2) surfaces. Liquid-fluid contact angle measurements using captive air
      bubbles were performed in different aqueous media (pure water, phosphate-buffered
      saline, and 10(-)(3) M KCl of two different pH values (pH = 3 and pH = 10) to
      study the copolymer films in their hydrated states relevant for biointerfacial
      phenomena. It was found that the graduation of the wettability of the copolymer
      films in the dry state is overall maintained upon immersion in aqueous solutions.
      The dependence of the wettability on the pH value of the aqueous medium could be
      related to the (de)protonation of the carboxylic groups.

PMID- 15982036
TI  - Impact of surface immobilization and solution ionic strength on the formal
      potential of immobilized cytochrome C.
AB  - Four different self-assembled monolayer (SAM) electrode systems were examined
      electrochemically in order to better understand surface charge effects on the
      redox thermodynamics of immobilized horse heart cytochrome c (cyt c).
      Neutralization of protein surface charge upon adsorption on anionic COOH
      terminated SAMs was found to cause substantial changes in the formal potential,
      as determined by cyclic voltammetry. For cyt c immobilized on negatively charged
      surfaces, the formal potential shifted to more negative values as the ionic
      strength was decreased, which is opposite to the trend displayed by solution cyt
      c. In contrast, immobilization to uncharged interfaces resulted in an ionic
      strength dependence for cyt c that is similar to its solution behavior. The
      results provide insight into the importance of surface charge on the formal
      potential of cyt c.

PMID- 15982037
TI  - Dehydration damage of domain-exhibiting supported bilayers: an AFM study on the
      protective effects of disaccharides and other stabilizing substances.
AB  - Atomic force microscopy (AFM) has been applied to characterize hydrated
      sphingomyelin/dioleoylphosphatidylcholine/cholesterol supported bilayers, after
      dehydration either in the absence or in the presence of several stabilizing
      substances. Such a study provides information about the effect of extreme
      environmental conditions on biological membranes and, in particular, on lipidic
      microdomains. Dehydration stress, indeed, is thought to cause both macroscopical
      damage and alterations of microdomains in biomembranes, leading to deleterious
      effects. These phenomena can be avoided if disaccharides are added during
      dehydration. In this work, we apply AFM imaging to directly visualize damage
      caused to supported lipid bilayers by water removal. We compare the efficiency of
      sucrose, trehalose, dextran, dimethyl sulfoxide, and glucose in preserving the
      structural integrity of domain-exhibiting model membranes. Finally, in addition
      to confirming previous findings, our results provide further insight into damage
      and alteration of microdomains in membranes as a consequence of stressful drying
      conditions.

PMID- 15982038
TI  - Synthesis of luminescent silicon nanopowders redispersible to various solvents.
AB  - Silicon nanopowder with a narrow size distribution was synthesized by a simple
      method, in which amorphous SiO(x) (x < 2) powder as starting material was
      annealed at high temperature and then etched by hydrofluoric acid (HF). Si
      nanoparticles thus obtained exhibited emission in the ultraviolet and visible
      regions under excitation at an energy corresponding to the direct band-gap
      transition. At the same time, they could be redispersed in various organic
      solvents such as octanol, toluene, etc., without surfactants or capping molecules
      on particle surfaces. X-ray diffraction and Fourier transform infrared
      spectroscopy were used to follow the change of components in the sample during
      annealing and HF etching processes, and the size distribution and dispersion
      morphology of the nanoparticles in different solvents were revealed by
      transmission electron microscopy analysis.

PMID- 15982039
TI  - Adsorption of nonionic surfactant mixtures at the hydrophilic solid-solution
      interface.
AB  - The adsorption of the mixed nonionic surfactants, monododecyl triethylene glycol
      (C2EO3) and monododecyl octaethylene glycol (C12EO8), at the hydrophilic silica
      solution interface has been studied by specular neutron reflectivity. The
      adsorption at the solid-solution interface is compared with that previously
      measured at the air-solution interface. The marked differences that are observed
      are explained in terms of the different packing constraints or preferred
      curvature arising from the disparity in the respective headgroup dimensions.

PMID- 15982040
TI  - Reversible covalent patterning of self-assembled monolayers on gold and silicon
      oxide surfaces.
AB  - This paper describes the generation of reversible patterns of self-assembled
      monolayers (SAMs) on gold and silicon oxide surfaces via the formation of
      reversible covalent bonds. The reactions of (patterned) SAMs of 11-amino-1
      undecanethiol (11-AUT) with propanal, pentanal, decanal, or terephthaldialdehyde
      result in dense imine monolayers. The regeneration of these imine monolayers to
      the 11-AUT monolayer is obtained by hydrolysis at pH 3. The (patterned)
      monolayers were characterized by Fourier transform infrared reflection absorption
      spectroscopy, X-ray photoelectron spectroscopy, contact angle and electrochemical
      measurements, and atomic force microscopy. Imines can also be formed by
      microcontact printing of amines on terephthaldialdehyde-terminated substrates.
      Lucifer Yellow ethylenediamine was employed as a fluorescent amine-containing
      marker to visualize the reversible covalent patterning on a terephthaldialdehyde
      terminated glass surface by confocal microscopy. These experiments demonstrate
      that with reversible covalent chemistry it is possible to print and erase
      chemical patterns on surfaces repeatedly.

PMID- 15982041
TI  - Functional monolayers for improved resistance to protein adsorption:
      oligo(ethylene glycol)-modified silicon and diamond surfaces.
AB  - The interaction of proteins with semiconductors such as silicon and diamond is of
      great interest for applications such as electronic biosensing. We have
      investigated the use of covalently bound oligo(ethylene glycol), EG, monolayers
      on diamond and silicon to minimize nonspecific protein adsorption. Protein
      adsorption was monitored by fluorescence scanning as a function of the length of
      the ethylene glycol chain (EG3 through EG6) and the terminal functional group
      (methyl- versus hydroxyl-terminated EG3 monolayer). More quantitative
      measurements were made by eluting adsorbed avidin from the surface and measuring
      the intensity of fluorescence in the solution. The attachment chemistry of the
      tri(ethylene glycol) molecules and monolayer orientation was studied by X-ray
      photoelectron spectroscopy. Improvement in the selectivity of surfaces modified
      with EG functionality was demonstrated in two model biosensing assays. We find
      that high-quality EG monolayers are formed on silicon and diamond and that these
      EG3 monolayers are as effective as EG3 self-assembled monolayers on gold at
      resisting nonspecific avidin adsorption. These results show promise for use of
      silicon and diamond materials in many potential applications such as biosensing
      and medical implants.

PMID- 15982042
TI  - Adsorption of organic matter at mineral/water interfaces. 6. Effect of inner
      sphere versus outer-sphere adsorption on colloidal stability.
AB  - The effects of the adsorption modes of several low molecular weight (LMW) organic
      anions (maleate, oxalate, and citrate) on the colloidal stability of corundum
      water suspensions have been examined using electrokinetic and shear yield stress
      (tau(y)) measurements over a broad range of pH conditions and LMW organic anion
      concentrations. Consistent with previous studies, increasing concentrations of
      maleate, oxalate, and citrate progressively shift the electrokinetic isoelectric
      point and pH of the maximum shear yield stress (tau(y,max)) to more acidic
      conditions. Due to its predominant electrostatic driving force for adsorption,
      outer-spherically adsorbed maleate possesses a very limited ability to charge
      reverse the corundum-water interface or bind to the negatively charged corundum
      surface. By contrast, inner-spherically adsorbed oxalate and citrate can
      significantly charge reverse the corundum-water interface, with the extent of
      charge reversal being related to the relative binding strengths of the oxalate
      and citrate anions. Adsorbed maleate, oxalate, and citrate generate steric
      barriers to interparticle approach, leading to substantial reductions in the
      magnitude of tau(y,max) at low to intermediate concentrations of those LMW
      anions. At the highest anion concentrations investigated, however, increases in
      tau(y,max) are observed, and can be attributed to the formation of bridging
      Al(III)-organic surface precipitates, as suggested by in situ attenuated total
      reflectance Fourier transform infrared spectroscopic measurements of corundum
      oxalate suspensions at high oxalate concentrations. The extent of precipitate
      formation is greatest for the corundum-oxalate system due to the strong
      dissolution-enhancing properties of the inner-spherically adsorbed oxalate anion
      (i.e., its ability to generate enhanced concentrations of dissolved Al(III) which
      can then participate in precipitate formation). The effects of the LMW organic
      anion adsorption modes on both the forms of the measured tau(y) versus pH data,
      and the ability to quantitatively compare tau(y) and zeta potential data measured
      at different corundum concentrations, are also discussed.

PMID- 15982043
TI  - Oxygen plasma-treatment effects on Si transfer.
AB  - Oxygen plasma-treatment is commonly used to increase the hydrophilicity of
      poly(dimethylsiloxane) (PDMS) stamps used for microcontact printing (muCP)
      aqueous-based inks. Review of the literature reveals that a wide range of plasma
      parameters are currently employed to modify stamp surfaces. However, little is
      known about the effect of these parameters (e.g., power, chamber pressure,
      duration) on the undesirable transfer of low-molecular-weight silicon-containing
      fragments from the stamps that commonly occurs during muCP. To study the effect
      of oxygen plasma-treatment on Si transfer, unpatterned PDMS stamps were treated
      with oxygen plasma under various conditions and used to stamp deionized water on
      plasma-activated poly(methyl methacrylate) (PMMA) substrates. Once stamped, the
      PMMA substrates were analyzed with X-ray photoelectron spectroscopy (XPS) to
      quantify and characterize silicon present on the substrate surface. In addition,
      used PDMS stamps were analyzed with scanning electron microscopy (SEM) to observe
      topographical changes that occur during oxygen plasma-treatment. XPS results show
      that all plasma treatments studied significantly reduced the amount of Si
      transfer from the treated stamps during muCP as compared to untreated PDMS stamps
      and that the source of transfer is residual PDMS fragments not removed by oxygen
      plasma. SEM results show that, although the treated stamps undergo a variety of
      topographical changes, no correlation exists between stamp topography and extent
      of Si transfer from the stamps.

PMID- 15982044
TI  - Surface rheology of PEO-PPO-PEO triblock copolymers at the air-water interface:
      comparison of spread and adsorbed layers.
AB  - The dilatational rheological properties of monolayers of poly(ethylene oxide)
      poly(propylene oxide)-poly(ethylene oxide)-type block copolymers at the air-water
      interface have been investigated by employing an oscillating ring trough method.
      The properties of adsorbed monolayers were compared to spread layers over a range
      of surface concentrations. The studied polymers were PEO26-PPO39-PEO26 (P85),
      PEO103-PPO40-PEO103 (F88), and PEO99-PPO65-PEO99 (F127). Thus, two of the
      polymers have similar PPO block size and two of them have similar PEO block size,
      which allows us to draw conclusions about the relationship between molecular
      structure and surface dilatational rheology. The dilatational properties of
      adsorbed monolayers were investigated as a function of time and bulk solution
      concentration. The time dependence was found to be rather complex, reflecting
      structural changes in the layer. When the dilatational modulus measured at
      different concentrations was replotted as a function of surface pressure, one
      unique master curve was obtained for each polymer. It was found that the
      dilatational behavior of spread (Langmuir) and adsorbed (Gibbs) monolayers of the
      same polymer is close to identical up to surface concentrations of approximately
      0.7 mg/m2. At higher coverage, the properties are qualitatively alike with
      respect to dilatational modulus, although some differences are noticeable.
      Relaxation processes take place mainly within the interfacial layers by a
      redistribution of polymer segments. Several conformational transitions were shown
      to occur as the area per molecule decreased. PEO desorbs significantly from the
      interface at segmental areas below 20 A(2), while at higher surface coverage, we
      propose that segments of PPO are forced to leave the interface to form a mixed
      sublayer in the aqueous region.

PMID- 15982045
TI  - Photoinduced electron transfer in self-assembled monolayers of porphyrin
      fullerene dyads on ITO.
AB  - Two porphyrin-fullerene dyads were synthesized to form self-assembled monolayers
      (SAMs) on indium-tin oxide (ITO) electrode, with either ITO-porphyrin-fullerene
      or ITO-fullerene-porphyrin orientations. The dyads contain two linkers for
      connecting the porphyrin and fullerene moieties and enforcing them essentially to
      similar geometries of the donor-acceptor pair, and two linkers to ensure the
      attachment of the dyads to the ITO surface with two desired opposite
      orientations. The transient photovoltage responses (Maxwell displacement charge)
      were measured for the dyad films covered by insulating LB films, thus ensuring
      that the dyads interact only with the ITO electrode. The direction of the
      electron transfer was from the photoexcited dyad to ITO independent of the dyad
      orientation. The response amplitude for the ITO-fullerene-porphyrin structure,
      where the primary intramolecular electron-transfer direction coincides with the
      direction of the final electron transfer from the dyad to ITO, was 25 times
      stronger than that for the opposite ITO-porphyrin-fullerene orientation of the
      dyad. Static photocurrent measurements in a liquid electrochemical cell, however,
      show only a minor orientation effect, indicating that the photocurrent generation
      is controlled by the processes at the SAM-liquid interface.

PMID- 15982046
TI  - Amphiphilic treelike rods at interfaces: layered stems and circular aggregation.
AB  - Amphiphilic dendron-rod molecules with three hydrophilic poly(ethylene oxide)
      (PEO) branches attached to a hydrophobic octa-p-phenylene rod stem were
      investigated for their ability to form two-dimensional micellar structures on a
      solid surface. A treelike shape of the molecules was reported to be a major
      factor in the formation of nonplanar micellar structures in solution and in the
      bulk state (cylindrical and spherical). We observed that in these treelike
      amphiphilic molecules the hydrophilic terminated dendron branches assemble
      themselves in surface monolayers with the formation of two-dimensional layered or
      circular micellar structures. We suggested the formation of the planar ribbon
      like structures with interdigitated layering within the loosely packed monolayers
      and circular, ringlike structures (2D circular aggregates) in the precollapsed
      state.

PMID- 15982047
TI  - Effects of degassing on the long-range attractive force between hydrophobic
      surfaces in water.
AB  - The long-ranged attractions between hydrophobic amorphous fluoropolymer surfaces
      are measured in water with and without dissolved air. An atomic force microscope
      is used to obtain more than 500 measured jump-in distances, which yields
      statistically reliable results. It is found that the range of the attraction and
      its variability is generally significantly decreased in deaerated water as
      compared to normal, aerated water. However, the range and strength of the
      attraction in deaerated water remain significantly greater than the van der Waals
      attraction for this system. The experimental observations are consistent with (1)
      nanobubbles being primarily responsible for the long-ranged attraction in normal
      water, (2) nanobubbles not being present in deaerated water when the surfaces are
      not in contact, and (3) the attraction in the absence of nanobubbles being most
      probably due to the approach to the separation-induced spinodal cavitation of the
      type identified by Berard et al. [J. Chem. Phys. 1993, 98, 7236]. It is argued
      that the measurements in deaerated water reveal the bare or pristine hydrophobic
      attraction unobscured by nanobubbles.

PMID- 15982048
TI  - Second-order nonlinear optical properties of the Ag(111)/electrolyte interface in
      the presence of self-assembled monolayers containing conjugated pi systems. I.
      Alpha-functionalized terthiophene films on Ag(111).
AB  - The nonlinear optical properties of self-assembled monolayers obtained from
      bonding two different alpha-functionalized terthiophenes (alpha-T3) to (111)
      silver electrode surfaces have been investigated using second harmonic generation
      (SHG). The two (alpha-T3) compounds used were functionalized with alkane chains
      of different lengths (C8 and C4), and each was terminated with a thiol anchoring
      group. A nitrile group was attached to the terminal thiophene ring of the (alpha
      T3) compound with the C4 chain. The orientation of the polarization of the
      incident beam was changed systematically and gradually between "p" and "s"
      orientation and the SH signal (isotropic and anisotropic contributions) analyzed
      in both directions ("P" and "S"). The symmetry of the system was reduced by the
      presence of the adlayers from C3v to C3. The dependence on the applied potential
      and the incident wavelength has also been studied. The relative magnitudes and
      phases of the various second-order tensor elements have been estimated and
      compared with the values for a bare surface. A resonance process in the (alpha
      T3) pi moiety has been investigated, and from this, the effective "band-gap"
      energies of the organic semiconductor SAMs (i.e., the energy difference between
      the pi-pi bands) have been estimated.

PMID- 15982049
TI  - Indirect reduction of aryldiazonium salts onto cathodically activated platinum
      surfaces: formation of metal-organic structures.
AB  - Platinum phases of general formula [Pt(n-), M+, MX] can be electrogenerated from
      cathodic polarization in dry dimethylformamide containing a supporting
      electrolyte, MX. The reaction of these electrogenerated Pt phases as reducing
      agent with aryldiazonium salts was investigated for preparing controlled metal
      organic interfaces and characterizing the reactivity of the "reduced platinum
      phases". In a two-step process, the "reduced platinum phase" locally reacts with
      aryldiazonium salts, leading to the attachment of aryl groups onto the metal
      surface in the previously modified areas. Detailed experiments using cyclic
      voltammetry, X-ray photoelectron spectroscopy (XPS), and in situ electrochemical
      atomic force microscopy (EC-AFM) were carried out to follow the reaction in
      solution with the example of NaI as supporting electrolyte (MX = NaI). These
      studies demonstrate the irreversible attachment of aryl groups onto the platinum
      electrode. Comparison between the direct electroreduction of aryldiazonium
      compounds (4-nitrophenyl- and 4-bromophenyldiazonium) on a platinum electrode and
      their reaction with [Pt2-, Na+, NaI] suggests that a similar general mechanism is
      responsible for the grafting. However in the second case, no applied potential is
      required to stimulate the binding thanks to the reductive properties of [Pt2-,
      Na+, NaI]. Competitive reduction of the organic layer and growth of the layer
      were observed and analyzed as a function of the injected charge used to initially
      produce [Pt2-, Na+, NaI]. Similar reactions are highly probable with other MX
      salts owing to the redox properties observed for this type of platinum phase
      ([Pt(n-), M+, MX]).

PMID- 15982050
TI  - Many-particle tracking with nanometer resolution in three dimensions by
      reflection interference contrast microscopy.
AB  - We have developed and characterized a method, based on reflection interference
      contrast microscopy, to simultaneously determine the three-dimensional positions
      of multiple particles in a colloidal monolayer. To evaluate this method, the
      interaction of 6.8 microm (+/-5%) diameter lipid-derivatized silica microspheres
      with an underlying planar borosilicate substrate is studied. Measured colloidal
      height distributions are consistent with expectations for an electrostatically
      levitated colloidal monolayer. The precision of the method is analyzed using
      experimental techniques in addition to computational bootstrapping algorithms. In
      its present implementation, this technique achieves 16 nm lateral and 1 nm
      vertical precision.

PMID- 15982051
TI  - Bacterial printing press that regenerates its ink: contact-printing bacteria
      using hydrogel stamps.
AB  - This paper describes the use of micropatterned agarose stamps prepared by molding
      against PDMS masters to print patterns of bacteria on agar plates.
      Topographically patterned agarose stamps were inked with suspensions of bacteria;
      these stamps generated patterns of bacteria with features as small as 200 microm
      over areas as large as 50 cm2. Stamps with many small features (>200 microm) were
      used to study patterns of bacteria growing on media containing gradients of small
      molecules; stamps with larger features (>750 microm) were used to print different
      strains of bacteria simultaneously. The stamp transfers only a small percentage
      of cells that are on its surface to the agar at a time; it is thus possible to
      replica-pattern hundreds of times with a single inking. The use of soft stamps
      provides other useful functions. Stamps are easily customized to provide a range
      of patterns. When culture media is included in the agarose stamp, cells divide
      and thrive on the surface. The resulting "living stamp" regenerates its "ink" and
      can be used to pattern surfaces repetitively for a month. This method is rapid,
      reproducible, convenient, and can be used to control the pattern, spacing, and
      orientation between colonies of different bacteria.

PMID- 15982052
TI  - Interactions between titanium dioxide and phosphatidyl serine-containing
      liposomes: formation and patterning of supported phospholipid bilayers on the
      surface of a medically relevant material.
AB  - Titanium is widely used in biomedical applications. Its mechanical properties and
      biocompatibility, conferred by a layer of oxide present on its surface, make
      titanium the material of choice for various implants (artificial hip and knee
      joints, dental prosthetics, vascular stents, heart valves). Furthermore, the high
      refractive index of titanium oxide is advantageous in biosensor applications
      based on optical detection methods. In both of the above fields of application,
      novel surface modification strategies leading to biointeractive interfaces (that
      trigger specific responses in biological systems) are continuously sought. In
      this report, we investigate the interactions between TiO2 and phosphatidyl serine
      containing liposomes, present a novel approach for preparing supported
      phospholipid bilayers (SPBs) of various compositions on TiO2, and use the unique
      ability of liposomes to distinguish between different surfaces to create SPB
      corrals on SiO2/TiO2 structured substrates. These results represent an important
      first step toward the design of biointeractive interfaces on titanium oxide
      surfaces that are based on a cell membrane-like environment.

PMID- 15982053
TI  - Orientations of nematic liquid crystals on surfaces presenting controlled
      densities of peptides: amplification of protein-peptide binding events.
AB  - We report a study of the orientations of nematic liquid crystals (LCs) in contact
      with peptide-modified, oligoethylene glycol-containing, self-assembled monolayers
      (SAMs). The SAMs were formed on gold films that were prepared by physical vapor
      deposition at an oblique angle of incidence. Two peptides were investigated: the
      optimized substrate for the Src protein kinase (IYGEFKKKC) and the synthetic
      equivalent of that peptide after kinase modification (IpYGEFKKKC). Polarization
      modulation-infrared reflectance absorbance spectroscopy (PM-IRRAS) was used to
      characterize the relative areal densities and orientations of these peptides at
      the interface. We conclude that the presence/absence of a phosphate group can
      influence the maximum packing density of immobilized peptide. We evaluated the
      orientations of the nematic liquid crystal 5CB in contact with these peptide
      modified surfaces by using polarized microscopy. The time required for the
      nematic phase of 5CB to exhibit long-range orientational ordering (uniform
      alignment) was found to increase with increasing areal densities of immobilized
      peptide. We also found that the specific binding event between anti
      phosphotyrosine IgG and the surface-immobilized phosphopeptide leads to an
      increase in the time required for the liquid crystal to achieve uniform anchoring
      (exceeding the experimentally accessible time scales). These results, when
      combined, suggest that the areal density and size of biomolecules at an interface
      can influence the time required for liquid crystals in contact with
      nanostructured surfaces to exhibit long-range orientational order. Finally, we
      illustrate the potential utility of this system by demonstrating that liquid
      crystals can be used to amplify and report protein binding events occurring on a
      spatially resolved peptide array.

PMID- 15982054
TI  - Relevance of electrokinetic theory for "soft" particles to bacterial cells:
      implications for bacterial adhesion.
AB  - Bacterial cells and other biological particles carry charged macromolecules on
      their surface that form a "soft" ion-permeable layer. In this paper, we test the
      applicability of an electrokinetic theory for soft particles to characterize the
      electrophoretic mobility (EPM) and adhesion kinetics of bacterial cells. The
      theory allows the calculation of two parameters--the electrophoretic softness and
      the fixed charged density--that define the characteristics of the polyelectrolyte
      layer at the soft particle surface. The theory also allows the calculation of an
      outer-surface potential that may better predict the electrostatic interaction of
      soft particles with solid surfaces. To verify its relevance for bacterial cells,
      the theory was applied to EPM measurements of two well-characterized Escherichia
      coli K12 mutants having lipopolysaccharide (LPS) layers of different lengths and
      molecular compositions. Results showed that the obtained softness and fixed
      charge density were not directly related to the known characteristics of the LPS
      of the selected strains. Interaction energy profiles calculated from Derjaguin
      Landau-Verwey-Overbeek (DLVO) theory were used to interpret bacterial deposition
      (adhesion) rates on a pure quartz surface. The outer surface potential failed to
      predict the low attachment efficiencies of the two bacterial strains. The lack of
      success in the application of the theory for soft particles to bacterial cells is
      attributed to chemical and physical heterogeneities of the polyelectrolyte layer
      at the cell surface.

PMID- 15982055
TI  - Immunosensing based on site-directed immobilization of antibody fragments and
      polymers that reduce nonspecific binding.
AB  - Antibody Fab'-fragments can be directly coupled onto gold, and the space between
      the fragments can be filled with protein repellent disulfide bearing polymers.
      Coupling of the antibody Fab'-fragments, and thus both the amount of nonspecific
      binding and antigen binding but also the ability to regenerate the layer, is
      dependent on the immobilization procedure. First, the immobilization has taken
      place by coupling the Fab'-fragments to the surface and thereafter attaching the
      polymer in the remaining space between the antibodies. Second, the Fab'-fragments
      have been added after the surface has been coated by polymer. Third, the Fab'
      fragments and polymer have been added onto the surface from the same solution. Up
      to 80% of the antigen could be removed during regeneration, if proper
      concentrations of polymer and Fab'-fragments were immobilized onto the gold
      surface. Only about 60% of the antigen could be removed, when the fragments were
      coupled directly onto a clean Au surface before the polymer or if low
      concentrations of polymer were attached onto gold before the Fab'-fragments. The
      first immobilization method, however, showed the highest response to antigen.

PMID- 15982056
TI  - Molecular composition and orientation in myelin figures characterized by coherent
      anti-stokes Raman scattering microscopy.
AB  - The molecular organization inside myelin figures of various surfactants are
      studied by laser scanning coherent anti-Stokes Raman scattering (CARS) microscopy
      that permits three-dimension vibrational imaging. The resonant CARS signals from
      CH2 and H2O stretch vibrations are used to probe the surfactant and water
      molecules inside the myelin figures formed of C12E3, lecithin, and Aerosol OT.
      The polarization sensitivity of CARS is used to analyze the orientation of the
      CH2 groups and the H2O molecules. The CARS images suggest that the myelin figure
      is a concentric lamellar structure with alternating surfactant bilayers and
      partially ordered water layers. No sizable water core is observed in the CARS
      images at the lateral resolution of 0.3 microm and the axial resolution of 0.75
      microm. The CARS data are verified by confocal fluorescence microscopy with FITC
      and DOPE-rhodamine labeling the water and bilayers, respectively. The
      relationship between the molecular composition and ordering inside the myelin
      figures and the surfactant structure has been investigated.

PMID- 15982057
TI  - Groove-spanning behavior of lipid membranes on microfabricated silicon
      substrates.
AB  - We report on a spreading behavior of phospholipid membranes that arise from a
      lump of phospholipid (a lipid source) on topographically patterned substrates
      immersed in an aqueous solution. Microgrooves with well-defined shapes were
      prepared on Si111 surfaces by anisotropic etching in an alkaline solution. A
      spreading front that consists of membrane lobes and a single lipid bilayer was
      observed on the patterned silicon substrates by utilizing fluorescence
      interference contrast (FLIC) microscopy. FLIC images indicate that the membrane
      lobes span the microgrooves, while the underlying single lipid bilayer spread
      along the surface of the microgrooves. In fact, fluorescent polystyrene
      nanoparticles could be encapsulated in the microgrooves that were completely
      covered with the membrane lobes. The groove-spanning behavior of membrane lobes
      is discussed in terms of a balance between adhesion and bending energies of lipid
      bilayers.

PMID- 15982058
TI  - DNA compaction onto hydrophobic surfaces by different cationic surfactants.
AB  - DNA compaction by alkyltrimethylammonium surfactants at hydrophobized silica
      surfaces and the effect of the counterion, as well as the hydrocarbon chain
      length, was investigated by in situ null-ellipsometry. In addition, DNA
      compaction in the presence of a gemini surfactant, hexyl-alpha,omega
      bis(dodecyldimethylammonium bromide), was studied. The type of cationic
      amphiphile used was found not to have a pronounced effect on the mixed DNA
      cationic surfactant adsorbed layer thickness, although the surface concentration
      excess for the mixed layers seemed to follow the same trend as that for DNA-free
      surfactant layers. Interestingly, it was also found that the stability of the
      mixed adsorbed layer largely depends on the cationic surfactant used.

PMID- 15982059
TI  - Enantioselective recognition of phenylalanine by a chiral amphiphilic macrocycle
      at the air-water interface: a copper-mediated mechanism.
AB  - The synthesis of a new chiral amphiphilic calix[4]resorcinarene, tetrakis(N
      methylprolyl)tetraundecylcalix[4]resorcinarene (L-RA-Pro), bearing four L-prolyl
      moieties at the macrocyclic upper rim and four undecyl chains at the lower rim is
      described. This synthesis has been carried out via a Mannich-type reaction of L
      proline and formaldehyde. It has been shown by means of Langmuir balance
      technique that L-RA-Pro self-assemble as well-defined monomolecular layers at the
      air-water interface. The effect of various cations on the stability of these
      monolayers has been studied. The experiments reveal that while there is a slight
      stabilization effect of K+, Cd2+, Co2+, Mg2+, and Ni2+, there is a high decrease
      in the collapse pressure in the presence of Cu(II) cation, showing that
      monolayers of L-RA-Pro, formed at the air-water interface, have a certain
      selectivity for copper(II) ions with regard to other cations tested. This
      supramolecular complex exhibits enantioselective recognition properties vs
      phenylalanine; the mechanism of this interaction is discussed.

PMID- 15982060
TI  - Relationship between interfacial forces measured by colloid-probe atomic force
      microscopy and protein resistance of poly(ethylene glycol)-grafted poly(L-lysine)
      adlayers on niobia surfaces.
AB  - Adsorbed layers of "comb-type" copolymers consisting of PEG chains grafted onto a
      poly(l-lysine) (PLL) backbone on niobium oxide substrates were studied by colloid
      probe AFM in order to characterize the interfacial forces associated with
      coatings of varying architectures (PEG/PLL ratios and PEG chain lengths) and
      their relevance to protein resistance. The steric and electrostatic forces
      measured varied substantially with the architecture of the PLL-g-PEG copolymers.
      Varying the ionic strength of the buffer solutions enabled discrimination between
      electrostatic and steric-entropic contributions to the net interfacial force. For
      high PEG grafting densities the steric component was most prominent, but at low
      ionic strengths and high grafting densities, a repulsive electrostatic surface
      force was also observed; its origin was assigned to the niobia charges beneath
      the copolymer, as insufficient protonated amine groups in the PLL backbone were
      available for compensation of the oxide surface charges. For lower grafting
      densities and lower ionic strengths there was a substantial attractive
      electrostatic contribution arising from interaction of the electrical double
      layer arising from the protonated amine groups, with that of the silica probe
      surface (as under low ionic strength conditions, the electrical double layer was
      thicker than the PEG layer). For these PLL-g-PEG coatings the net interfacial
      force can thus be a markedly varying superposition of electrostatic and steric
      entropic contributions, depending on various factors. The force curves correlate
      with protein adsorption data, demonstrating the utility of AFM colloid-probe
      force measurements for quantitative analysis of surface forces and how they
      determine interfacial interactions with proteins. Such characterization of the
      net interfacial forces is essential to elucidate the multiple types of
      interfacial forces relevant to the interactions between PLL-g-PEG coatings and
      proteins and to advance interpretation of protein adsorption or repellence beyond
      the oversimplified steric barrier model; in particular, our data demonstrate the
      importance of an ionic-strength-dependent minimum PEG layer thickness to screen
      the electrostatic interactions of charged interfaces.

PMID- 15982061
TI  - Sum-frequency observation of solvent structure at model chromatographic
      interfaces: acetonitrile-water and methanol-water systems.
AB  - The adsorption of methanol-D2O and acetonitrile-D2O solutions at model
      chromatographic interfaces (octadecylsiloxane and quartz) was studied using sum
      frequency spectroscopy. Methanol did not adsorb at either interface in detectable
      quantities, while acetonitrile adsorbs at the octadecylsiloxane- and quartz
      solution interfaces in a concentration-dependent manner and is well ordered at
      the interface. Adsorption of acetonitrile was decreased by the addition of KCl at
      10 and 100 mM. Acetonitrile adsorption was also observed during simulated
      gradient elution, demonstrating that adsorption of acetonitrile occurs on a time
      scale relevant to actual chromatographic separations. Examination of the OH
      stretch spectra of acetonitrile-H2O and methanol-H2O solutions at the interface
      revealed concentration-dependent changes in the acetonitrile-H2O spectra that are
      consistent with hydrogen bonding between interfacial water and acetonitrile,
      indicating that interfacial water is involved in mediating acetonitrile
      adsorption. The OH stretch spectra of methanol-H2O solutions showed no such
      changes.

PMID- 15982062
TI  - Thin-film transistors based on Langmuir-Blodgett films of heteroleptic
      bis(phthalocyaninato) rare earth complexes.
AB  - An ordered molecular assembly of heteroleptic bis(phthalocyaninato) rare earth
      complexes M(Pc)[Pc(OC8H17)8] [M = Tb, Lu; H2Pc = phthalocyanine; H2Pc(OC8H17)8 =
      2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyanine] has been fabricated by the
      Langmuir-Blodgett (LB) technique and characterized by surface pressure-area
      isotherms, electronic absorption and polarized electronic absorption
      spectroscopy, low-angle X-ray diffraction, and atomic force microscopy. The
      molecular ordering in the LB multilayer film on SiO2 substrate was made into a p
      channel field effect transistor (FET), which was generally operated in the
      enhanced mode. The energy levels of the highest occupied molecular orbital and
      the lowest unoccupied molecular orbital as well as the energy band diagram can be
      deduced from the electrochemical measurement results. The charge mobilities of
      Tb(Pc)[Pc(OC8H17)8] and Lu(Pc)[Pc(OC8H17)8] were calculated to be about 6.4 x 10(
      4) and 1.7 x 10(-3) cm2 V(-1) s(-1), respectively.

PMID- 15982063
TI  - Assessment of 4-(dimethylamino)pyridine as a capping agent for gold
      nanoparticles.
AB  - Gold nanoparticles stabilized with 4-(dimethylamino)pyridine (DMAP) were prepared
      by ligand exchange and phase transfer (toluene/water) of functionalized gold
      nanoparticles. DMAP-protected gold nanoparticles are water-soluble, positively
      charged, and fairly monodisperse (6.2 +/- 0.9 nm). To understand the scope of
      this interesting system, the details of the binding of DMAP to gold nanoparticles
      were investigated. The adsorption of DMAP onto gold surfaces was studied by
      electrochemistry and surface plasmon resonance. It is concluded that of the three
      most likely binding modes, the one involving the pyridine nitrogen binding to the
      gold surface, as suggested previously (Gittins, D. I.; Caruso, F. Angew. Chem.,
      Int. Ed. 2001, 40, 3001), is consistent with experimental data. Other 4
      substituted pyridines were also assessed as capping agents. The solubility in
      toluene and basicity of the incoming ligand, as well as the ability to form
      charged nanoparticles, determine whether ligand exchange and subsequent phase
      transfer of the nanoparticles occur. The solubility and stability of the DMAP
      protected gold nanoparticles were studied as a function of pH using UV-visible
      spectroscopy and transmission electron microscopy (TEM). These nanoparticles are
      soluble and stable over a wide pH range (5.0-12.8). It was found that excess DMAP
      is necessary for both the preparation and the stability of the DMAP-protected
      gold nanoparticles.

PMID- 15982064
TI  - The interaction of boronic acid-substituted viologens with pyranine: the effects
      of quencher charge on fluorescence quenching and glucose response.
AB  - The fluorescence sensing of several monosaccharides using boronic acid
      substituted viologen quenchers in combination with the fluorescent dye pyranine
      (HPTS) is reported. In this two-component sensing system, fluorescence quenching
      by the viologen is modulated by monosaccharides to provide a fluorescence signal.
      A series of viologen quenchers with different charges were prepared and tested
      for their ability both to quench the fluorescence of HPTS and to sense changes in
      glucose concentration in aqueous solution at pH 7.4. Both quenching efficiency
      and sugar sensing were found to be strongly dependent upon viologen charge. The
      molar ratio between HPTS and each of the viologen quenchers was varied in order
      to obtain an optimal ratio that provided a fairly linear fluorescence signal
      across a physiological glucose concentration range. Both the quenching and sugar
      sensing results are explained by electrostatic interaction between dye and
      quencher.

PMID- 15982066
TI  - Core/shell nanocomposite based on the local polarization and its
      electrorheological behavior.
AB  - Aimed at the increase of electrorheological effect, a novel core/shell material
      was prepared by the combination of mechanochemical activity and sol-gel
      technique. The structure analyses X-ray diffraction, Fourier transform infrared
      spectrometry, scanning electron microscopy, and energy-dispersive spectrometry
      showed that a modified kaolinite/titanium oxide nanocomposite consisted of the
      mechanochemically activated kaolinite/NaCl complex coated by titanium oxide. A
      distinct enhancement of the electrorheological activity was found by using such
      particles dispersed in silicone oil than those of kaolinite or titanium oxide
      alone under a direct current electric field. Modified kaolinite/titanium oxide
      electrorheological fluid has a larger dielectric constant enhancement
      deltaepsilon', and a strong interfacial polarization occurs with a clear
      dielectric loss peak around 2 kHz. Doping NaCl into the core (kaolinite) by the
      mechanochemical activation and limiting the transferring of the ions by the shell
      (titanium oxide) may increase the interfacial polarizability of particles and
      induce a high electrorheological effect.

PMID- 15982065
TI  - Tunable magnetic arrangement of iron oxide nanoparticles in situ synthesized on
      the solid substrate from diblock copolymer micelles.
AB  - Hexagonal arrangement of iron oxide nanoparticles was fabricated by utilizing a
      single-layered film of diblock copolymer micelles. The synthesis was directly
      performed on the solid substrate by oxygen plasma with preserving the dimensional
      order of micelles so that separate procedures for synthesis and deposition of
      nanoparticles were not necessary. Since the oxygen plasma treatment also
      eliminated polymers, pure patterns of iron oxide nanoparticles were obtained.
      Moreover, easy control over the size of nanoparticles enabled us to selectively
      create a ferrimagnetic or a superparamagnetic pattern of iron oxide nanoparticles
      without altering the fabrication process.

PMID- 15982067
TI  - Bioelectrochemically functional nanohybrids through co-assembling of proteins and
      surfactants onto carbon nanotubes: facilitated electron transfer of assembled
      proteins with enhanced faradic response.
AB  - Preparation and bioelectrochemical properties of functional nanohybrids through
      co-assembling of hemeproteins (i.e., horseradish peroxidase, hemoglobin,
      myoglobin and cytochrome c) and surfactants onto carbon nanotubes (CNTs) are
      described. The prepared protein-surfactant-CNT nanohybrids are found to possess
      facilitated interfacial electron transfer of the proteins with enhanced faradic
      responses. The enhancements are ascribed for the first time to the properties of
      the surfactants for facilitation of protein electrochemistry and the improved
      portion of electroactive proteins assembled, of which the latter assignment is
      closely associated with the electrochemical and structural properties of the
      nanotubes and the three-dimensional architecture of the CNT film confined onto
      the glassy carbon electrode. It is proposed that the single and/or small bundles
      of the nanotubes in the CNT film electrode can be rationally functionalized with
      surfactants to be functional nanoelectrodes capable of facilitating electron
      transfer of proteins. The three-dimensional confinement of these functional
      nanowires onto the GC electrode essentially increases the portion of
      electroactive proteins assembled in the nanohybrids. These properties of the
      protein-surfactant-CNT nanohybrids, combined with the bioelectrochemical
      catalytic activity, could make them useful for development of bioelectronic
      devices and investigation of protein electrochemistry at functional interfaces.

PMID- 15982068
TI  - Amphiphilic azo polymer spheres, colloidal monolayers, and photoinduced
      chromophore orientation.
AB  - In this work, azobenzene-containing colloidal spheres have been fabricated and
      used to construct photoresponsive monolayers. The colloidal spheres were prepared
      from an amphiphilic azobenzene-containing random copolymer through hydrophobic
      aggregation of the polymer chains, which was induced by adding the selective
      solvent (H2O) into a THF solution of the polymer. The size and size distribution
      of the spheres depended on the initial concentration of the azo polymer in THF
      and the H2O/THF ratio. Adjusting those factors and optimizing other preparation
      conditions, uniform colloidal spheres could be obtained. Monolayers composed of
      hexagonally close-packed colloidal spheres were prepared by the capillary-force
      driven method. The colloidal monolayers showed obvious dichroism after laser
      irradiation due to the photoinduced azo-chromophore orientation occurred in the
      spheres. The orientation order parameter was related to the irradiation time and
      estimated to be 0.09 at the photostationary state. The colloidal spheres and
      their monolayers can potentially be used as building blocks or media for
      reversible optical data storage, photo-switching, sensors, and other photo-driven
      devices.

PMID- 15982069
TI  - Preparation of sub-micrometer silica shells using poly(1-methylpyrrol-2
      ylsquaraine).
AB  - Poly(1-methylpyrrol-2-ylsquaraine) precipitates from reaction solution as
      uniformly spherical particles with a diameter of 1.3 microm. Upon heating, the
      particles reduce in diameter until extinction at approximately 630 degrees C.
      Treatment of the particles with 9:1 tetraethoxysilane:ethanol solution, and
      subsequent hydrolysis in dilute acid, results in a polymer core-silica shell
      structure. Removal of the core, upon heating to 660 degrees C, results in an
      amorphous silica shell with a diameter half that of the initial template sphere.
      It has been found that the silica shells produced by this method are able to
      encapsulate organic dyes upon soaking of the shells in chloroform solutions of
      the dyes, and further washings with fresh chloroform did not remove the dyes. The
      production of crystalline titanium dioxide shells was also achieved through the
      use of the polysquaraine particles as a spherical template.

PMID- 15982070
TI  - Porous polymer films and honeycomb structures based on amphiphilic dendronized
      block copolymers.
AB  - Fabrication of honeycomb patterned films from our synthesized amphiphilic
      dendronized block copolymer by "on-solid surface spreading" method and "on-water
      spreading" method was reported for the first time in this paper. The comparison
      of the two methods indicated honeycomb-patterned films with smaller size, and
      larger surface density of micropores can be fabricated by spreading on water but
      with lower regular arrangement. Furthermore, several influencing factors on the
      formation of the honeycomb structure and the different morphologies, such as the
      concentration of the copolymer solution and the relative humidity in the
      atmosphere and the substrates, were investigated. The results showed that
      comparably high relative humidity from 80% to 95% was needed, and the mica plate
      as a spreading substrate was suitable to form orderly porous films for such a
      copolymer. The best ordered pattern could be formed from the copolymer with
      concentration of 1.00 mg/mL at the relative humidity of 85% using a mica plate.
      Besides, strong periodicity, regularity, and a large, defect-free area were
      notable, which made this structure extremely interesting for applications for
      templated molecular objects formed via intramolecular metal or metal oxide
      synthesis.

PMID- 15982071
TI  - Nonspherical assemblies generated from polystyrene-b-poly(L-lysine)
      polyelectrolyte block copolymers.
AB  - This report describes the aqueous solution self-assembly of a series of
      polystyrene(m)-b-poly(L-lysine)n block copolymers (m = 8-10; n = 10-70). The
      polymers are prepared by ring-opening polymerization of epsilon-benzyloxycarbonyl
      L-lysine N-carboxyanhydride using amine terminated polystyrene macroinitiators,
      followed by removal of the benzyloxycarbonyl side chain protecting groups. The
      critical micelle concentration of the block copolymers determined using the
      pyrene probe technique shows a parabolic dependence on peptide block length
      exhibiting a maximum at n = approximately 20 (m = 8) or n = approximately 60 (m =
      10). The shape and size of the aggregates has been studied by dynamic and static
      light scattering, small-angle neutron scattering (SANS), and analytical
      ultracentrifugation (AUC). Surprisingly, Holtzer and Kratky analysis of the
      static light scattering results indicates the presence of nonspherical,
      presumably cylindrical objects independent of the poly(L-lysine)n block length.
      This is supported by SANS data, which can be fitted well by assuming cylindrical
      scattering objects. AUC analysis allows the molecular weight of the aggregates to
      be estimated as several million g/mol, corresponding to aggregation numbers of
      several 10s to 100s. These aggregation numbers agree with those that can be
      estimated from the length and diameter of the cylinders obtained from the
      scattering results.

PMID- 15982072
TI  - Fabrication of densely packed titania nanosheet films on solid surface by use of
      Langmuir-Blodgett deposition method without amphiphilic additives.
AB  - Densely packed exfoliated nanosheet films such as Ti0.91O2, Ti0.8M0.2O2 (M = Co,
      Ni), Ti0.6Fe0.4O2, and Ca2Nb3O10 on solid substrates were prepared by the LB
      transfer method without any amphiphilic additives at the air-water interface.
      Nanosheet crystallites covered nearly 95% on the solid surface with minimum
      overlapping of nanosheets. The LB transfer method of the Ti0.91O2 nanosheet
      monolayer film is applicable for not only hydrophilic substrates such as quartz,
      silicon, indium-tin oxide (ITO), and glass but also the hydrophobic Au surface.
      On the basis of these points, the LB transfer method has advantages compared to
      the alternating layer-by-layer method, which makes use of oppositely charged
      polyelectrolytes such as poly(ethylenimine) (PEI). Adsorption of hydrophobic
      Ti0.91O2 nanosheets at the air-water interface is responsible for this LB
      transfer deposition method. The addition of tetrabutylammonium bromide into the
      subphase assisted the adsorption, causing an increase in the adsorbed amount of
      Ti0.91O2 nanosheets at the air-water interface.

PMID- 15982073
TI  - Investigations into the mechanism of adsorption of carbon nanotubes onto
      aminopropylsiloxane functionalized surfaces.
AB  - The factors that control carbon nanotube (CNT) adsorption onto aminopropyl
      siloxane (APS)-derivatized surfaces were investigated using two distinct types of
      well-characterized films with significant differences in their detailed
      structures. Both types of APS films showed a marked increase in CNT adsorption
      relative to untreated SiO2 surfaces but differed in the amount of CNTs adsorbed.
      To gain insight into the factors governing adsorption, the surface coverage of
      the CNTs was monitored as a function of the pH during the deposition, the
      surfactant used to suspend the CNTs, and the type and amount of salt added to the
      deposition solution. The adsorption is shown to be governed by electrostatic and
      VDW forces. In the case of complimentarily charged surfaces, the adsorption is
      proposed to occur through an ion exchange mechanism.

PMID- 15982074
TI  - An AC electrokinetic technique for collection and concentration of particles and
      cells on patterned electrodes.
AB  - We report an electrohydrodynamic effect arising from the application of
      alternating electric fields to patterned electrode surfaces. The AC fields were
      applied to dilute suspensions of latex microspheres enclosed between a patterned
      silicon wafer and an ITO-coated glass slide in a small chamber. The latex
      particles became collected in the center of the conductive "corrals" on the
      silicon wafer acting as bottom electrode. The particle collection efficiency and
      speed depended only on the frequency and strength of the field and were
      independent of the material properties of the particles or the electrodes. The
      leading effect in the particle collection process is AC electrohydrodynamics. We
      discuss how the electrohydrodynamic flows emerge from the spatially nonuniform
      field and interpret the experimental results by means of electrostatic and
      hydrodynamic simulations. The technique allows three-dimensional microfluidic
      pumping and transport by the use of two-dimensional patterns. We demonstrate on
      chip collection of latex particles, yeast cells, and microbes.

PMID- 15982075
TI  - Modeling of the hysteresis phenomena in finite-sized slitlike nanopores. Revision
      of the recent results by rigorous numerical analysis.
AB  - The systematic investigation of the hysteresis phenomena in finite-sized slitlike
      nanopores via the Aranovich-Donohue (AD) lattice density functional theory (LDFT)
      is presented. The new reliable quantitative modeling of the adsorption and
      desorption branch of the hysteresis loop, through the formation and movement of
      the curved meniscus, is formulated. As a result, we find that our proposal, which
      closely mimics the experimental findings, can reproduce a rounded shape of the
      desorption branch of the hysteresis loop. On the basis of the exhausted
      commutations, we proved that the hysteresis loop obtained in the considered
      finite-sized slitlike geometry is of the H1 type of the IUPAC classification.
      This fundamental result and the other most important results do not confirm the
      results of the recent studies of Sangwichien et al., whereas they fully agree
      with the recent lattice studies due to Monson et al. We recognize that the nature
      of the hysteresis loops (i.e. position, width, shape, and the multiple steps)
      mainly depends on the value of the energy of both the adsorbate-adsorbate and
      adsorbate-adsorbent interactions; however, the first one is critical for the
      appearance of hysteresis. Thus, for relatively small adsorbate-adsorbate
      interactions, the adsorption-desorption process is fully reversible in the whole
      region of the bulk density. We show that the strong adsorbate-adsorbent
      interactions produce (also observed experimentally) multiple steps within
      hysteresis loops. Contrary to the other studies of the hysteresis phenomena in
      confined geometry via the LDFT formalism, we constructed both ascending and
      descending scanning curves, which are known from the experimental observations.
      Additionally, we consider the problem of the stability of both the obtained
      adsorption and desorption branches of the computed hysteresis loop in finite
      sized slitlike nanopores.

PMID- 15982076
TI  - Spreading dynamics of chain-like monolayers: a molecular dynamics study.
AB  - Using large-scale molecular dynamics simulations, we have shown previously that
      the spreading dynamics of sessile drops on solid surfaces can be described in
      detail using the molecular-kinetic theory of dynamic wetting. Here we present our
      first steps in extending this approach to investigate the spreading dynamics of
      Langmuir-Blodgett monolayers. We make use of a monolayer model originally
      developed by Karaborni and Toxvaerd, but somewhat simplified to facilitate large
      scale simulations. Our preliminary results are in good agreement with recent
      experimental observations and also support a molecular-kinetic interpretation in
      which the driving force for spreading is the lateral pressure in the monolayer.
      Away from equilibrium, initial spreading rates are constant and logarithmically
      dependent on pressure. However, near equilibrium, spreading is pseudo-diffusive
      and follows the square root of time. In both regimes the controlling factor is
      the equilibrium frequency of molecular displacements within the monolayer.

PMID- 15982077
TI  - Molecular dynamics simulation of the structural configuration of binary colloidal
      monolayers.
AB  - Molecular dynamics simulations of binary colloidal monolayers, i.e., monolayers
      consisting of mixtures of two different particle sizes, are presented. In the
      simulations, the colloid particles are located at an oil-water interface and
      interact via an effective dipole-dipole potential. In particular, the influence
      of the particle ratio on the configurations of the binary monolayers is
      investigated for two different relative interaction strengths between the
      particles, and the pair correlation functions corresponding to the binary
      monolayers are calculated. The simulations show that the binary monolayers can
      only form two-dimensional crystals for certain particle ratios, for example, 2:1,
      6:1, etc., while, for example, for a particle ratio of 7:1 the monolayers are
      found to be in a disordered, glassy state. The calculations also reveal that in
      analogy to the Wigner lattice the configurations are very sensitive to the
      relative interaction strength between the particles but not to the absolute
      magnitude of the interaction strength, even when particle size effects are taken
      into account. Consequently, it is argued that a comparison between the calculated
      configurations and actual binary particle monolayer systems could provide useful
      information on the relative interaction strength between large and small
      particles. Possible mechanisms giving rise to disparities in the interaction
      strength between large and small particles are described briefly.

PMID- 15982078
TI  - Measurement of the elastic modulus of single bacterial cellulose fibers using
      atomic force microscopy.
AB  - The ability of the atomic force microscope to measure forces with subnanonewton
      sensitivity at nanometer-scale lateral resolutions has led to its use in the
      mechanical characterization of nanomaterials. Recent studies have shown that the
      atomic force microscope can be used to measure the elastic moduli of suspended
      fibers by performing a nanoscale three-point bending test, in which the center of
      the fiber is deflected by a known force. We extend this technique by modeling the
      deflection measured at several points along a suspended fiber, allowing us to
      obtain more accurate data, as well as to justify the mechanical model used. As a
      demonstration, we have measured a value of 78 +/- 17 GPa for Young's modulus of
      bacterial cellulose fibers with diameters ranging from 35 to 90 nm. This value is
      considerably higher than previous estimates, obtained by less direct means, of
      the mechanical strength of individual cellulose fibers.

PMID- 15982079
TI  - Negative mood, self-focused attention, and the experience of physical symptoms:
      the joint impact hypothesis.
AB  - A joint impact hypothesis on symptom experience is introduced that specifies the
      role of negative mood and self-focus, which have been considered independently in
      previous research. Accordingly, negative affect only promotes symptom experience
      when people simultaneously focus their attention on the self. One correlational
      study and 4 experiments supported this prediction: Only negative mood combined
      with self-focus facilitated the experience (see the self-reports in Studies 1,
      2a, & 2b) and the accessibility (lexical decisions, Stroop task in Studies 3 & 4)
      of physical symptoms, whereas neither positive mood nor negative mood without
      self-focus did. Furthermore, the joint impact of negative mood and self-focused
      attention on momentary symptom experience remained significant after controlling
      for the influence of dispositional symptom reporting and neuroticism.

PMID- 15982080
TI  - Affective reactivity in language: the role of psychophysiological arousal.
AB  - Several studies have found that individuals with schizophrenia and their
      relatives, as well as healthy controls, exhibit greater language disturbance when
      discussing affectively negative as compared to positive or neutral topics. The
      goal of this study was to test the hypothesis that negative emotion impairs
      language production, at least in part by increasing physiological arousal. The
      authors had 35 healthy adults produce speech in response to affectively negative,
      positive, and neutral questions while the authors recorded heart rate and skin
      conductance. Participants displayed greater amounts of reference errors, higher
      heart rates, and a higher frequency of nonspecific skin conductance responses
      when discussing affectively negative as compared to positive or neutral topics.

PMID- 15982081
TI  - Cultures of moderation and expression: emotional experience, behavior, and
      physiology in Chinese Americans and Mexican Americans.
AB  - Ethnographic accounts suggest that emotions are moderated in Chinese cultures and
      expressed openly in Mexican cultures. The authors tested this notion by comparing
      subjective, behavioral, and physiological aspects of emotional responses to 3
      (warned, unwarned, instructed to inhibit responding) aversive acoustic startle
      stimuli in 95 Chinese Americans and 64 Mexican Americans. Subjective reports were
      consistent with ethnographic accounts; Chinese Americans reported experiencing
      significantly less emotion than Mexican Americans across all 3 startle
      conditions. Evidence from a nonemotional task suggested that these differences
      were not artifacts of cultural differences in the use of rating scales. Few
      cultural differences were found in emotional behavior or physiology, suggesting
      that these aspects of emotion are less susceptible to cultural influence.

PMID- 15982082
TI  - Body sensations associated with emotions in Raramuri Indians, rural Javanese, and
      three student samples.
AB  - Cultural variations in the associations of 12 body sensations with 7 emotions
      were studied in 2 rural samples from northern Mexico (n = 61) and Java, Indonesia
      (n = 99), with low exposure to Western influences and in 3 university student
      samples from Belgium (n = 75), Indonesia (n = 85), and Mexico (n = 123). Both
      parametric and nonparametric analyses suggest that findings from previous studies
      with only student samples (K. R. Scherer & H. G. Wallbott, 1994) were
      generalizable to the 2 rural samples. Some notable cultural deviations from
      common profiles were also identified. Implications of the findings for
      explanations of body sensations experienced with emotions and the cross-cultural
      study of emotions are discussed.

PMID- 15982083
TI  - The tie that binds? Coherence among emotion experience, behavior, and physiology.
AB  - Emotion theories commonly postulate that emotions impose coherence across
      multiple response systems. However, empirical support for this coherence
      postulate is surprisingly limited. In the present study, the authors (a) examined
      the within-individual associations among experiential, facial behavioral, and
      peripheral physiological responses during emotional responding and (b) assessed
      whether emotion intensity moderates these associations. Experiential, behavioral,
      and physiological responses were measured second-by-second during a film that
      induced amusement and sadness. Results indicate that experience and behavior were
      highly associated but that physiological responses were only modestly associated
      with experience and behavior. Intensity of amusement experience was associated
      with greater coherence between behavior and physiological responding; intensity
      of sadness experience was not. These findings provide new evidence about response
      system coherence in emotions.

PMID- 15982084
TI  - Enhanced memory for negatively emotionally charged pictures without selective
      rumination.
AB  - Emotionally charged materials have been found to elicit higher levels of recall
      in many studies. However, the use of slow presentations and/or uncontrolled
      retention intervals may have allowed subjects to rehearse emotional materials
      preferentially. The authors presented a series of 5 pictures (1 emotionally
      charged) at a rate of 4 pictures per second, precluding selective rehearsal. In
      Experiment 1, subjects recalled the pictures immediately or after performing an
      arithmetic task for 20 s. In Experiment 2, the pictures were described as to-be
      ignored distractors, and the memory test was unexpected. Stimulus emotionality
      greatly enhanced recall in all conditions. The speed of the presentations and the
      fact that enhancement did not spread to temporally adjacent items argues against
      some widely discussed mechanisms for emotional enhancement.

PMID- 15982085
TI  - Emotion-modulated performance and activity in left dorsolateral prefrontal
      cortex.
AB  - Functional MRI (fMRI) was used to examine the relationship between processing of
      pleasant and unpleasant stimuli and activity in prefrontal cortex. Twenty
      volunteers identified the colors in which pleasant, neutral, and unpleasant words
      were printed. Pleasant words prompted more activity bilaterally in dorsolateral
      prefrontal cortex (DLPFC) than did unpleasant words. In addition, pleasant words
      prompted more activity in left than in right DLPFC. Response speed to pleasant
      words was correlated with DLPFC activity. These data directly link positive
      affect, enhanced performance, and prefrontal activity, providing some of the
      first fMRI evidence supporting models of emotional valence and frontal brain
      asymmetry based on electroencephalography (EEG).

PMID- 15982086
TI  - Emotion as a thermostat: representing emotion regulation using a damped
      oscillator model.
AB  - The authors present in this study a damped oscillator model that provides a
      direct mathematical basis for testing the notion of emotion as a self-regulatory
      thermostat. Parameters from this model reflect individual differences in
      emotional lability and the ability to regulate emotion. The authors discuss
      concepts such as intensity, rate of change, and acceleration in the context of
      emotion, and they illustrate the strengths of this approach in comparison with
      spectral analysis and growth curve models. The utility of this modeling approach
      is illustrated using daily emotion ratings from 179 college students over 52
      consecutive days. Overall, the damped oscillator model provides a meaningful way
      of representing emotion regulation as a dynamic process and helps identify the
      dominant periodicities in individuals' emotions.

PMID- 15982087
TI  - Why we sing the blues: the relation between self-reflective rumination, mood, and
      creativity.
AB  - Past research has shown that creative behavior is associated with a higher risk
      for depression. The authors hypothesized that a 3rd underlying factor, namely,
      self-reflective rumination, may explain the connection. This hypothesis was
      examined in a sample of 99 undergraduate college students, using path analysis.
      The authors found that self-reported past depressive symptomatology was linked to
      increased self-reflective rumination. Rumination, in turn, was related to current
      symptomatology and to self-rated creative interests and objectively measured
      creative fluency, originality, and elaboration. No direct link existed between
      currently depressed mood and either creative interest or creative behavior. These
      results suggest that the association between depression and creativity is solely
      the result of rumination.

PMID- 15982088
TI  - Evaluating the MSCEIT V2.0 via CFA: comment on Mayer et al. (2003).
AB  - This investigation uncovered several substantial errors in the confirmatory
      factor analysis results reported by J. D. Mayer, P. Salovey, D. R. Caruso, and G.
      Sitarenios (see record 2003-02341-015). Specifically, the values associated with
      the close-fit indices (normed fit index, Tucker-Lewis Index, and root-mean-square
      error of approximation) are inaccurate. A reanalysis of the Mayer et al. subscale
      intercorrelation matrix provided accurate values of the close-fit indices, which
      resulted in different evaluations of the models tested by J. D. Mayer et al.
      Contrary to J. D. Mayer et al., the 1-factor model and the 2-factor model did not
      provide good fit. Although the 4-factor model was still considered good fitting,
      the non-constrained 4-factor model yielded a non-positive definite matrix, which
      was interpreted to be due to the fact that two of the branch-level factors
      (Perceiving and Facilitating) were collinear, suggesting that a model with 4
      factors was implausible.

PMID- 15982090
TI  - Emotional intensity of idiographic sad memories in depression predicts symptom
      levels 1 year later.
AB  - When cued with generic happy and sad words, depressed individuals have been found
      to articulate contextually impoverished memories of autobiographical events.
      Although this pattern predicts a worse symptomatic course of disorder in some
      depressed samples, longitudinal findings with the cue-word paradigm are
      inconsistent. To address the etiological significance of autobiographical
      memories outside the cue-word paradigm, the authors used an idiographic interview
      in which depressed participants generated memories of their happiest and saddest
      lifetime events. Each memory was coded for detail and emotional intensity. At a 1
      year follow-up, participants' levels of depressive symptoms were reassessed.
      Lower emotional intensity of saddest memories predicted higher levels of
      depressive symptoms at follow-up. Several implications for understanding sadness
      and emotional disclosure in depression are discussed.

PMID- 15982091
TI  - Visual awareness and the detection of fearful faces.
AB  - A commonly held view is that emotional stimuli are processed independently of
      awareness. Here, the authors parametrically varied the duration of a fearful face
      target stimulus that was backward masked by a neutral face. The authors evaluated
      awareness by characterizing behavioral performance using receiver operating
      characteristic curves from signal detection theory. Their main finding was that
      no universal objective awareness threshold exists for fear perception. Although
      several subjects displayed a behavioral pattern consistent with previous reports
      (i.e., targets masked at 33 ms), a considerable percentage of their subjects
      (64%) were capable of reliably detecting 33-ms targets. Their findings suggest
      that considerable information is available even in briefly presented stimuli
      (possibly as short as 17 ms) to support masked fear detection.

PMID- 15982092
TI  - Reciprocal associations between adolescent sexual activity and quality of youth
      parent interactions.
AB  - The authors examined differences in adolescents' relationships with their parents
      before and after adolescent first sexual activity. Participants were 13,570
      members of the core sample of the National Longitudinal Survey of Adolescent
      Health (Add Health) Waves 1 and 2. Path analyses examined changes in parent
      adolescent closeness, shared activities, and problem-focused interactions
      associated with changes in sexual activity separately for sons and daughters and
      for mothers and fathers. Race, religion, age, urbanicity, and parents' education
      were controls. Results confirm that increased problem-focused interactions and
      decreased parental closeness and shared activities both precede and follow
      adolescent sexual activity. Maintaining positive parental relations after
      adolescent first sexual activity is discussed as a means to reduce risks
      associated with sex.

PMID- 15982093
TI  - Attributions and anger in early marriage: wives are event-dependent and husbands
      are schematic.
AB  - Two types of attribution believed to predict anger in married couples were
      investigated. Wives' anger was expected to be predicted by event-dependent
      attributions, appraisals based on the unique aspects of one's current situation.
      Husbands' anger was expected to be predicted by schematic attributions,
      appraisals based on one's global sentiment in the relationship. Seventy-seven
      recently married couples attended 2 assessment sessions, and each couple
      identified 4 incidents pertaining to unresolved relationship issues. Participants
      rated their event-dependent attributions and their anger prior to a discussion
      for each incident. They also completed questionnaires regarding schematic
      attributions and relationship sentiment. Hierarchical linear modeling was used to
      distinguish between the 2 types of attribution. Strong support was found for the
      expected gender differences. Results suggest that wives are particularly
      attentive to the details of interpersonal interaction.

PMID- 15982094
TI  - Representations of early family relationships predict marital maintenance during
      the transition to parenthood.
AB  - Marital maintenance, which involves engaging in behaviors that maintain closeness
      and is critical to sustaining marital satisfaction, was examined in 234 husbands
      and wives across the transition to parenthood. Prenatal assessments of adults'
      attachment representations and memories of their parents' marriage during
      childhood predicted perceptions of maintenance in their own marriage prenatally
      and 24 months postpartum. Adults who dismiss the importance of early attachment
      and lack believable memories of their parents' marriage reported the lowest
      levels of prenatal maintenance. Adults who are preoccupied with their early
      relationships with parents and have negative memories of their parents' marriage
      reported the sharpest declines in maintenance postpartum. Family interventions
      that can help couples recognize and explore problems that may accompany
      parenthood are discussed.

PMID- 15982095
TI  - Family dynamics in adolescence affect midlife well-being.
AB  - This longitudinal study explores the association between family system
      characteristics measured during adolescence and later midlife well-being. Home
      interviews were held in the 1970s with 99 families with adolescents. Connection
      and individuation in the family system were coded from taped family interactions.
      Twenty-five years later, telephone interviews were conducted with 54 men and 120
      women (representing 82 families) who were adolescents in the 1970s interviews.
      Family experiences during adolescence predicted adult well-being 25 years later.
      In a structural equation model, there was a direct effect of family both on the
      adolescents' later marriage and on well-being at midlife; for men, marriage also
      affected well-being. The results support the importance of connection and
      individuation in the adolescent family for adult well-being.

PMID- 15982096
TI  - Marital adjustment, child-rearing disagreements, and overreactive parenting:
      predicting child behavior problems.
AB  - Using structural equation modeling, the authors evaluated the hypothesis that the
      relation between marital adjustment and children's behavior problems is mediated
      by child-rearing disagreements, whose effects are mediated by parents'
      overreactive discipline. In a community sample, fully or partially mediated
      models of internalizing and externalizing behavior problems of 3- to 7-year-old
      boys (N = 99) and girls (N = 104) were supported for mothers and fathers in 7 of
      8 cases. Child-rearing disagreements always mediated the relation of marital
      adjustment and child behavior problems, and overreactive discipline was a final
      mediator in 3 cases. More variance was accounted for in mothers' than fathers'
      ratings. For mothers' ratings, the most variance was accounted for in boys'
      externalizing and girls' internalizing behavior problems.

PMID- 15982097
TI  - Secondary traumatization in partners and parents of Dutch peacekeeping soldiers.
AB  - This study examines secondary traumatization among 708 partners and 332 parents
      of Dutch peacekeepers (i.e., personnel who participated in military actions
      implemented by international organizations such as the United Nations). Partners
      or parents of peacekeepers with 4 levels of posttraumatic stress symptoms were
      compared on posttraumatic stress, health problems, the quality of the marital
      relationship, and social support. In comparison with partners of peacekeepers
      without posttraumatic stress disorder (PTSD) symptoms, partners of peacekeepers
      with PTSD symptoms reported more sleeping and somatic problems, reported more
      negative social support, and judged the marital relationship as less favorable.
      No significant differences were found for parents. Thus, peacekeepers' stress
      reactions were related to various problems of their partners. A systemic approach
      to the treatment of persons with PTSD appears appropriate.

PMID- 15982098
TI  - Strangers at home: comment on Dirkzwager, Bramsen, Ader, and van der Ploeg
      (2005).
AB  - This comment summarizes the findings of the article by A. J. E. Dirkzwager, I.
      Bramsen, H. Ader, and H. M. van der Ploeg (2005; see record 2005-06518-006) and
      notes that it can serve as a reawakening about the immediate and long-term
      psychosocial consequences of war, not only for those troops who are deployed but
      also for the loved ones who await their return. The lessons learned once again-
      that the mental health of the returning peacekeeper parallels that of his or her
      partner, that partners of traumatized soldiers report more posttraumatic stress
      disorder symptoms, somatic and sleep problems, negative social support, and low
      marital morale than partners of nontraumatized soldiers--are consistent with
      systemic traumatology theory. This comment traces the historical and theoretical
      foundations that underlie the concept of secondary trauma (i.e., compassion
      fatigue) and discusses the implications for family psychology practice in helping
      veterans and their families recover from their ordeals.

PMID- 15982099
TI  - Families at risk: comment on Dirkzwager, Bramsen, Ader, and van der Ploeg (2005).
AB  - New findings from a study by A. J. E. Dirkzwager, I. Bramsen, H. Ader, and H. M.
      van der Ploeg (2005; see record 2005-06518-006) provide important empirical
      information on the adverse psychological and functional adjustment of families of
      former Dutch peacekeepers suffering from posttraumatic stress disorder (PTSD). In
      this comment the authors consider a few methodological limitations and issues for
      future study, including the need for intergenerational studies of the legacy of
      peacekeeping-related PTSD. Attention to considering the treatment needs of
      families of traumatized former peacekeepers is encouraged.

PMID- 15982100
TI  - When family members go to war--a systemic perspective on harm and healing:
      comment on Dirkzwager, Bramsen, Ader, and van der Ploeg (2005).
AB  - The article by A. J. E. Dirkzwager, I. Bramsen, H. Ader, and H. M. van der Ploeg
      (2005; see record 2005-06518-006) provides compelling evidence of trauma
      transmission of posttraumatic stress symptoms (PTSS) from male peacekeepers to
      their female partners. Given the rise in troop deployment throughout the globe
      and increased exposure of soldiers to combat violence, the investigation is
      highly relevant, important and timely, illustrating the broad systemic emotional
      toll on couples when partners go to war. The purpose of this comment is to
      recommend future research directions (a) to reveal the characteristics of those
      individuals, couples, and family members that may be predictive of vulnerability
      and resiliency to PTSS and its sequelae; (b) to understand the interrelationship
      of PTSS and secondary trauma, relationship adjustment, and social support; and
      (c) to develop and test intervention methods that may be effective in reducing
      PTSS and other psychosocial problems among peacekeepers, their partners, and
      other family members.

PMID- 15982101
TI  - Child-related disagreements, verbal aggression, and children's internalizing and
      externalizing behavior problems.
AB  - Dual-income parents (N = 122 couples) with an oldest child 18-60 months of age
      completed the Child-Rearing Disagreements Scale (E. N. Jouriles et al., 1991),
      the Child Behavior Checklist (T. M. Achenbach & L. A. Rescorla, 2000), and the
      Verbal Aggression subscale of the Conflicts and Problem-Solving Scale (P. K.
      Kerig, 1996). Replicating the results of E. N. Jouriles et al. (1991) and
      extending these findings to daughters and fathers, the authors found links
      between child-related disagreements and parental ratings of child behavior
      problems in this low-risk sample. There were no links between fathers' reports of
      verbal aggression and child behavior problems. Among mothers, however, use of
      verbal aggression mediated the link between child-related disagreements and
      ratings of sons' internalizing problems. Verbal aggression did not moderate the
      link between child-related disagreements and child behavior problems for either
      mothers or for fathers.

PMID- 15982102
TI  - Effects of economic pressure on marital conflict in Romania.
AB  - This study examined the interrelationships among economic pressure, maternal
      depression, social support, and marital conflict in a sample of 239 mothers in
      Romania. Data were collected through a school-based survey. Findings indicated
      that higher levels of economic pressure were associated with higher levels of
      marital conflict. Economic pressure was also associated with higher marital
      conflict indirectly through increased maternal depression and lowered social
      support. The present results were similar to those obtained in studies conducted
      among U.S. samples.

PMID- 15982103
TI  - Parent and peer predictors of physical aggression and conflict management in
      romantic relationships in early adulthood.
AB  - Violence between romantic partners is widespread, but developmental precursors of
      perpetration and victimization are little understood. Among participants followed
      from birth to 23 years of age, familial and extrafamilial childhood and
      adolescent relationships were examined in connection with couple violence in
      early adulthood. Predictors included early childhood physical abuse and
      witnessing of parental partner violence, features of parent-child interactions at
      the age of 13 years, and close friendship quality at the age of 16 years.
      Controlling for early familial violence, intrusive or overly familiar behavior in
      videotaped parent-child collaborations at 13 years of age consistently predicted
      violence perpetration and victimization in early adulthood. Friendship quality at
      the age of 16 years contributed over and above familial predictors. Understanding
      the role of both familial and extrafamilial close relationship precursors may
      lead to effective strategies for ameliorating the problem of romantic partner
      violence.

PMID- 15982104
TI  - Religiosity and the socioemotional adjustment of adolescent mothers and their
      children.
AB  - This study assessed the impact of religiosity on the socioemotional and
      behavioral outcomes of 91 adolescent mothers and their offspring over 10 years.
      Religiosity was defined as involvement in church and contact with and dependence
      on church officials and members. Mothers classified as high in religious
      involvement had significantly higher self-esteem and lower depression scores,
      exhibited less child abuse potential, and had higher occupational and educational
      attainment than mothers classified as low in religious involvement; differences
      remained when multiple factors, such as stress and grandmother support, were held
      constant. Children with more religious mothers had fewer internalizing and
      externalizing problems at 10 years of age, with maternal adjustment mediating
      this relationship. Religiosity, through increased social support, served as a
      protective factor for teenaged mothers and their children.

PMID- 15982105
TI  - The taxometrics of marriage: is marital discord categorical?
AB  - This study used taxometric methods to investigate the latent structure of the
      construct of marital adjustment as indexed by the Marital Adjustment Test (MAT;
      H. J. Locke & K. M. Wallace, 1959). That is, the authors examined whether marital
      adjustment is best thought of as a "dimension" of adjustment only or whether
      there also are categorical differences between "discordant" and "nondiscordant"
      couples. Analyses of data provided by 447 couples married for approximately 2
      years provided converging evidence for a latent category of marital discord,
      suggesting that marital discord can be viewed as a qualitatively distinct state
      experienced by approximately 20% of the couples in the current sample.
      Implications for marital assessment are outlined.

PMID- 15982106
TI  - Perceptions of parental involvement and support as predictors of college
      students' persistence in a science curriculum.
AB  - As technological and scientific skills are increasingly needed, finding that
      science students encounter significant problems in their academic program causes
      serious concern. The authors examined how perceived parental involvement and
      support predict college students' persistence in science based on J. P. Connell
      and J. G. Wellborn's (1991) theoretical model: Perceived parental involvement and
      support should foster student persistence by promoting students' competence,
      autonomy, and relatedness. Results suggest that perceived parental autonomy
      supports predicted scientific persistence partly through students' autonomy.
      Perceived parental involvement, although unrelated to persistence, was a
      significant predictor of autonomy and relatedness. Results suggest that perceived
      parental involvement and support have specific roles in predicting student self
      processes and achievement, highlighting the importance of sustaining parents'
      contribution for college students.

PMID- 15982107
TI  - The influence of parent education and family income on child achievement: the
      indirect role of parental expectations and the home environment.
AB  - This study examined the process of how socioeconomic status, specifically
      parents' education and income, indirectly relates to children's academic
      achievement through parents' beliefs and behaviors. Data from a national, cross
      sectional study of children were used for this study. The subjects were 868 8-12
      year-olds, divided approximately equally across gender (436 females, 433 males).
      This sample was 49% non-Hispanic European American and 47% African American.
      Using structural equation modeling techniques, the author found that the
      socioeconomic factors were related indirectly to children's academic achievement
      through parents' beliefs and behaviors but that the process of these relations
      was different by racial group. Parents' years of schooling also was found to be
      an important socioeconomic factor to take into consideration in both policy and
      research when looking at school-age children.

PMID- 15982108
TI  - Longitudinal pathways to psychological adjustment among Black youth living in
      single-parent households.
AB  - A 5-wave model linking family and maternal functioning to youth psychological
      adjustment was tested with 139 single-mother-headed African American families
      with young adolescents (mean age = 11 years at recruitment) living in the rural
      South. Structural equation modeling indicated that an accumulation of family risk
      factors at Wave 1 was linked with maternal psychological functioning at Wave 2,
      which forecast competence-promoting parenting practices at Wave 3. These
      parenting practices indirectly forecast youth externalizing and internalizing
      behaviors 2 years later at Wave 5, through youth self-regulation at Wave 4. The
      hypothesized model was retested, controlling for Wave 1 youth externalizing and
      internalizing behaviors. All paths remained significant, indicating that the
      model accounted for change in youth psychological adjustment across 4 years.

PMID- 15982109
TI  - The interpersonal process model of intimacy in marriage: a daily-diary and
      multilevel modeling approach.
AB  - This study used daily reports of interactions in marriage to examine predictions
      from the conceptualization of intimacy as the outcome of an interpersonal
      process. Both partners of 96 married couples completed daily diaries assessing
      self-disclosure, partner disclosure, perceived partner responsiveness, and
      intimacy on each of 42 consecutive days. Multivariate multilevel modeling
      revealed that self-disclosure and partner disclosure both significantly and
      uniquely contributed to the contemporaneous prediction of intimacy. Perceived
      partner responsiveness partially mediated the effects of self-disclosure and
      partner disclosure on intimacy. Global marital satisfaction, relationship
      intimacy, and demand-withdraw communication were related to daily levels of
      intimacy. Implications for the importance of perceived partner responsiveness in
      the intimacy process for married partners are discussed.

PMID- 15982110
TI  - Siblings in domestically violent families: experiences of interparent conflict
      and adjustment problems.
AB  - This research examines whether siblings in domestically violent families differ
      in experiences of interparent conflict and whether such differences are
      associated with differences in children's adjustment. Participants included 112
      sibling pairs and their mothers temporarily residing in domestic violence
      shelters. Children completed measures of their experiences of interparent
      conflict, and children and mothers reported on children's adjustment problems.
      Cross-sibling correlations for experiences of interparent conflict were low to
      moderate. Sibling differences in threat appraisals of interparent conflict were
      associated with sibling differences in internalizing problems. Differences in
      self-blame appraisals were associated with differences in internalizing and
      externalizing problems. The direction of the relations indicated that the sibling
      who felt more threatened by or more at fault for interparent conflict experienced
      more adjustment problems. These findings suggest the potential utility of
      individually assessing sibling experiences of interparent conflict and tailoring
      interventions individually.

PMID- 15982111
TI  - The perceptual determinants of person construal: reopening the social-cognitive
      toolbox.
AB  - Guided by a heuristic account of social-cognitive functioning, researchers have
      attempted to identify the cognitive benefits that derive from a categorical
      approach to person construal. While revealing, this work has overlooked the fact
      that, prior to the application of categorical thinking as an economizing mental
      tool, perceivers must first extract category-triggering information from
      available stimulus cues. It is possible, therefore, that basic perceptual
      processes may also contribute to people's propensity to view others in a category
      based manner. This possibility was explored in 3 experiments in which the authors
      investigated the ease with which perceivers can extract categorical and identity
      based knowledge from faces under both optimal and suboptimal (i.e., inverted
      faces, blurred faces, rapidly presented faces) processing conditions. The results
      confirmed that categorical knowledge is extracted from faces more efficiently
      than identity-related knowledge, a finding that underscores the importance of
      perceptual operations in the generation of categorical thinking.

PMID- 15982112
TI  - Moral conviction: another contributor to attitude strength or something more?
AB  - Attitudes held with strong moral conviction (moral mandates) were predicted to
      have different interpersonal consequences than strong but nonmoral attitudes.
      After controlling for indices of attitude strength, the authors explored the
      unique effect of moral conviction on the degree that people preferred greater
      social (Studies 1 and 2) and physical (Study 3) distance from attitudinally
      dissimilar others and the effects of moral conviction on group interaction and
      decision making in attitudinally homogeneous versus heterogeneous groups (Study
      4). Results supported the moral mandate hypothesis: Stronger moral conviction led
      to (a) greater preferred social and physical distance from attitudinally
      dissimilar others, (b) intolerance of attitudinally dissimilar others in both
      intimate (e.g., friend) and distant relationships (e.g., owner of a store one
      frequents), (c) lower levels of good will and cooperativeness in attitudinally
      heterogeneous groups, and (d) a greater inability to generate procedural
      solutions to resolve disagreements.

PMID- 15982113
TI  - Changing circumstances, disrupting habits.
AB  - The present research investigated the mechanisms guiding habitual behavior,
      specifically, the stimulus cues that trigger habit performance. When usual
      contexts for performance change, habits cannot be cued by recurring stimuli, and
      performance should be disrupted. Thus, the exercising, newspaper reading, and TV
      watching habits of students transferring to a new university were found to
      survive the transfer only when aspects of the performance context did not change
      (e.g., participants continued to read the paper with others). In some cases, the
      disruption in habits also placed behavior under intentional control so that
      participants acted on their current intentions. Changes in circumstances also
      affected the favorability of intentions, but changes in intentions alone could
      not explain the disruption of habits. Furthermore, regardless of whether contexts
      changed, nonhabitual behavior was guided by intentions.

PMID- 15982114
TI  - Why do interracial interactions impair executive function? A resource depletion
      account.
AB  - Three studies investigated the veracity of a resource depletion account of the
      impairment of inhibitory task performance after interracial contact. White
      individuals engaged in either an interracial or same-race interaction, then
      completed an ostensibly unrelated Stroop color-naming test. In each study, the
      self-regulatory demands of the interaction were either increased (Study 1) or
      decreased (Studies 2 and 3). Results revealed that increasing the self-regulatory
      demands of an interracial interaction led to greater Stroop interference compared
      with control, whereas reducing self-regulatory demands led to less Stroop
      interference. Manipulating self-regulatory demands did not affect Stroop
      performance after same-race interactions. Taken together, the present studies
      point to resource depletion as the likely mechanism underlying the impairment of
      cognitive functioning after interracial dyadic interactions.

PMID- 15982115
TI  - The cultural grounding of personal relationship: enemyship in North American and
      West African worlds.
AB  - Three studies investigated the implicit constructions of reality associated with
      cultural differences in enemyship (personal relationship of hatred, malice, and
      sabotage). Results of interview (Study 1; N = 98) and questionnaire (Study 2; N =
      166) research indicated that enemyship was more prominent among Ghanaian
      participants than among U.S. participants. Additional evidence located a
      potential source of these differences in different constructions of relationship.
      Responses linked the prominence of enemyship to constructions of relationship as
      inherent, enduring connection (interdependent models). Responses linked the sense
      of freedom from enemyship to constructions of relationship as the discretionary
      product of atomistic selves (independent models). An experiment among Ghanaian
      participants (Study 3; N = 48) provided evidence that increasing experience of
      inherent connection can be sufficient to increase accessibility of enemyship.
      Results help to illuminate the cultural grounding of personal relationship and
      other phenomena that are typically invisible in mainstream theory and research.

PMID- 15982116
TI  - Chewing on it can chew you up: effects of rumination on triggered displaced
      aggression.
AB  - Ruminating about a provocation increases the likelihood of displaced aggression
      following a minor annoyance (trigger). In Study 1, provoked participants who
      ruminated for 25 min were more aggressive toward a fumbling confederate than were
      distracted participants. Provocation-induced negative affect was positively
      related to aggression but only among those who ruminated. Study 2 conceptually
      replicated Study 1 and also found that the more negatively people reacted to the
      trigger, the more likely the trigger was to increase displaced aggression. Study
      3 replicated the findings of Studies 1 and 2 by using an 8-hr rumination period.
      All 3 studies suggest that ruminating about a provocation increases the
      likelihood that a minor triggering annoyance will increase displaced aggression.

PMID- 15982117
TI  - Self-enhancement among high-exposure survivors of the September 11th terrorist
      attack: resilience or social maladjustment?
AB  - The authors examined self-enhancing bias as a predictor of adjustment among
      individuals in or near the World Trade Center during the September 11, 2001,
      terrorist attacks. Resilience was defined from categorical and continuous
      analyses of both participant self-report and friend and relative ratings of
      adjustment. Self-enhancement was associated with a resilient outcome, ratings of
      better adjustment prior to September 11th, greater positive affect, and reduced
      perceptions of social constraints. Additional analyses indicated that self
      enhancers' reduced symptom levels were fully mediated by their low perceived
      social constraints. However, consistent with previous evidence suggesting a
      social cost to self-enhancement, at 18 months post-September 11th, self
      enhancers' friends and relatives also rated them as decreasing in social
      adjustment and as being less honest.

PMID- 15982118
TI  - Attachment, self-esteem, worldviews, and terror management: evidence for a
      tripartite security system.
AB  - On the basis of prior work integrating attachment theory and terror management
      theory, the authors propose a model of a tripartite security system consisting of
      dynamically interrelated attachment, self-esteem, and worldview processes. Four
      studies are presented that, combined with existing evidence, support the
      prediction derived from the model that threats to one component of the security
      system result in compensatory defensive activation of other components. Further,
      the authors predicted and found that individual differences in attachment style
      moderate the defenses. In Studies 1 and 2, attachment threats motivated worldview
      defense among anxiously attached participants and motivated self-enhancement
      (especially among avoidant participants), effects similar to those caused by
      mortality salience. In Studies 3 and 4, a worldview threat and a self-esteem
      threat caused attachment-related proximity seeking among fearful participants and
      avoidance of proximity among dismissing participants. The authors' model provides
      an overarching framework within which to study attachment, self-esteem, and
      worldviews.

PMID- 15982119
TI  - Lost in the wilderness: terror management, action orientation, and nature
      evaluation.
AB  - The authors propose that wilderness is intrinsically associated with death, and,
      consequently, terror management concerns may promote more negative evaluations of
      wilderness. Consistent with this, wilderness inspired more thoughts about death
      than either cultivated nature or urban environments (Study 1), and death
      reminders reduced perceived beauty of wilderness (Study 2). The authors further
      suggest that active self-regulation facilitates suppression of the dark side of
      wilderness. Consistent with this, action orientation was positively related to
      perceived beauty of wilderness (Study 3), and after viewing wilderness, action
      oriented individuals were more efficient at suppressing the association between
      wilderness and death than state-oriented individuals (Study 4). Direct death
      reminders overruled the effects of action orientation on nature evaluation (Study
      5), presumably because direct death reminders are difficult to suppress even for
      action-oriented individuals.

PMID- 15982120
TI  - Competition, cooperation, and the effects of others on me.
AB  - Four studies were conducted to test the notion that whether one competes against
      or cooperates with a comparison target can serve as an important determinant of
      the direction (contrast or assimilation) of self-evaluative social comparison
      effects. In Study 1, cooperative-competitive orientation was treated as an
      individual difference variable, and it was shown that social comparison led to
      contrast for individuals with a more competitive orientation, whereas
      assimilation occurred for individuals with a more cooperative orientation. Study
      2 replicated this result, treating cooperative-competitive orientation as a
      contextual variable. In Study 3, it was demonstrated that to obtain this pattern
      of results it is not necessary for perceivers to believe that they will be either
      competing or cooperating with the comparison target. Simply activating the
      relevant concepts is sufficient. The final studies demonstrated that competition
      activates a "difference" focus and cooperation activates a "similarity" focus.

PMID- 15982121
TI  - Timing, sequencing, and executive control in repetitive movement production.
AB  - The authors demonstrate that the timing and sequencing of target durations
      require low-level timing and executive control. Sixteen young (M-sub(age) = 19
      years) and 16 older (M-sub(age) = 70 years) adults participated in 2 experiments.
      In Experiment 1, individual mean-variance functions for low-level timing
      (isochronous tapping) and the sequencing of multiple targets (rhythm production)
      revealed (a) a dissociation of low-level timing and sequencing in both age
      groups, (b) negligible age differences for low-level timing, and (c) large age
      differences for sequencing. Experiment 2 supported the distinction between low
      level timing and executive functions: Selection against a dominant rhythm and
      switching between rhythms impaired performances in both age groups and induced
      pronounced perseveration of the dominant pattern in older adults.

PMID- 15982122
TI  - Self-motion perception during locomotor recalibration: more than meets the eye.
AB  - Do locomotor aftereffects depend specifically on visual feedback? In 7
      experiments, 116 college students were tested, with closed eyes, at stationary
      running or at walking to a previewed target after adaptation, with closed eyes,
      to treadmill locomotion. Subjects showed faster inadvertent drift during
      stationary running and increased distance (overshoot) when walking to a target.
      Overshoot seemed to saturate (i.e., reach a ceiling) at 17% after as little as 1
      min of adaptation. Sidestepping at test reduced overshoot, suggesting motor
      specificity. But inadvertent drift effects were decreased if the eyes were open
      and the treadmill was drawn through the environment during adaptation, indicating
      that these effects involve self-motion perception. Differences in expression of
      inadvertent drift and of overshoot after adaptation to treadmill locomotion may
      have been due to different sets of ancillary cues available for the 2 tasks. Self
      motion perception is multimodal.

PMID- 15982123
TI  - Stimulus selectivity of figural aftereffects for faces.
AB  - Viewing a distorted face induces large aftereffects in the appearance of an
      undistorted face. The authors examined the processes underlying this adaptation
      by comparing how selective the aftereffects are for different dimensions of the
      images including size, spatial frequency content, contrast, and color. Face
      aftereffects had weaker selectivity for changes in the size, contrast, or color
      of the images and stronger selectivity for changes in contrast polarity or
      spatial frequency. This pattern could arise if the adaptation is contingent on
      the perceived similarity of the stimuli as faces. Consistent with this, changing
      contrast polarity or spatial frequency had larger effects on the perceived
      identity of a face, and aftereffects were also selective for different individual
      faces. These results suggest that part of the sensitivity changes underlying the
      adaptation may arise at visual levels closely associated with the representation
      of faces.

PMID- 15982124
TI  - Reduced Stroop interference for opponent colors may be due to input factors:
      evidence from individual differences and a neural network simulation.
AB  - Sensory or input factors can influence the strength of interference in the
      classic Stroop color-word task. Specifically, in a single-trial computerized
      version of the Stroop task, when color-word pairs were incongruent, opponent
      color pairs (e.g., the word BLUE in yellow) showed reduced Stroop interference
      compared with nonopponent color pairs (e.g., BLUE in red). In addition,
      participants' color discrimination ability was measured by standard color vision
      tests (i.e., Farnsworth-Munsell 100-Hue Test and Ishihara plates). Error rates in
      the Farnsworth-Munsell test correlated positively with the amount of Stroop
      interference. Neural network simulations (variants of J. D. Cohen, K. Dunbar, &
      J. L. McClelland's, 1990, model) showed that only a distributed trichromatic
      input layer was able to simulate these findings. Thus, sensory input from the
      color system needs to be incorporated into current accounts of the Stroop effect.

PMID- 15982125
TI  - Dynamic aspects of stimulus-response correspondence: evidence for two mechanisms
      involved in the Simon effect.
AB  - It has been recently proposed that the time course of the Simon effect may vary
      across tasks, which might reflect different types of stimulus-response (S-R)
      transmissions (E. Wascher, U. Schatz, T. Kuder, & R. Verleger, 2001). The authors
      tested this notion in 4 experiments by comparing Simon effects evoked by
      horizontal and vertical S-R arrangements. The temporal properties of the effect,
      as well as lateralized readiness potential-difference waves, indicated a fast and
      transient influence of the horizontal, but a slow and sustained influence of the
      vertical spatial stimulus feature on performance. Additional evidence for this
      temporal dissociation was obtained in experiments that induced a shortening or
      lengthening of the mean response time. Thus, the data strongly indicate that
      there are 2 temporally dissociable mechanisms involved in generating the Simon
      effect for horizontal and vertical S-R relations.

PMID- 15982126
TI  - Action comprehension: deriving spatial and functional relations.
AB  - A perceived action can be understood only when information about the action
      carried out and the objects used are taken into account. It was investigated how
      spatial and functional information contributes to establishing these relations.
      Participants observed static frames showing a hand wielding an instrument and a
      potential target object of the action. The 2 elements could either match or
      mismatch, spatially or functionally. Participants were required to judge only 1
      of the 2 relations while ignoring the other. Both irrelevant spatial and
      functional mismatches affected judgments of the relevant relation. Moreover, the
      functional relation provided a context for the judgment of the spatial relation
      but not vice versa. The results are discussed in respect to recent accounts of
      action understanding.

PMID- 15982127
TI  - Calibration, information, and control strategies for braking to avoid a
      collision.
AB  - This study explored visual control strategies for braking to avoid collision by
      manipulating information about speed of self-motion. Participants watched
      computer-generated displays and used a brake to stop at an object in the path of
      motion. Global optic flow rate and edge rate were manipulated by adjusting eye
      height and ground-texture size. Stopping distance, initiation of braking, and the
      magnitude of brake adjustments were influenced by both optical variables, but
      global optic flow rate had a stronger effect. A new model is introduced according
      to which braking is controlled by keeping the perceived ideal deceleration, based
      in part on global optic flow rate, within a "safe" region between 0 and the
      maximum deceleration of the brake.

PMID- 15982128
TI  - Parafoveal semantic processing of emotional visual scenes.
AB  - The authors investigated whether emotional pictorial stimuli are especially
      likely to be processed in parafoveal vision. Pairs of emotional and neutral
      visual scenes were presented parafoveally (2.1 degrees or 2.5 degrees of visual
      angle from a central fixation point) for 150-3,000 ms, followed by an immediate
      recognition test (500-ms delay). Results indicated that (a) the first fixation
      was more likely to be placed onto the emotional than the neutral scene; (b)
      recognition sensitivity (A') was generally higher for the emotional than for the
      neutral scene when the scenes were paired, but there were no differences when
      presented individually; and (c) the superior sensitivity for emotional scenes
      survived changes in size, color, and spatial orientation, but not in meaning. The
      data suggest that semantic analysis of emotional scenes can begin in parafoveal
      vision in advance of foveal fixation.

PMID- 15982129
TI  - The integration of object levels and their content: a theory of global/local
      processing and related hemispheric differences.
AB  - This article presents and tests the authors' integration hypothesis of
      global/local processing, which proposes that at early stages of processing, the
      identities of global and local units of a hierarchical stimulus are represented
      separately from information about their respective levels and that, therefore,
      identity and level information have to be integrated at later stages. It further
      states that the cerebral hemispheres differ in their capacities for these binding
      processes. Three experiments are reported in which the integration hypothesis was
      tested. Participants had to identify a letter at a prespecified level with the
      viewing duration restricted by a mask. False reporting of the letter at the
      nontarget level was predicted to occur more often when the integration of
      identity and level could fail. This was the case. Moreover, visual-field effects
      occurred, as expected. Finally, a multinomial model was constructed and fitted to
      the data.

PMID- 15982130
TI  - Response selection modulates visual search within and across dimensions.
AB  - In feature search tasks, uncertainty about the dimension on which targets differ
      from the nontargets hampers search performance relative to a situation in which
      this dimension is known in advance. Typically, these cross-dimensional costs are
      associated with less efficient guidance of attention to the target. In the
      present study, participants either had to perform a feature search task or had to
      perform a nonsearch task, that is, respond to a target presented without
      nontargets. The target varied either in one dimension or across dimensions. The
      results showed similar effects both in search and nonsearch conditions:
      Preknowledge of the target dimension gave shorter response times than when the
      dimension was unknown. Similar results were found using a trial-by-trial cueing.
      It is concluded that effects that typically have been attributed to early top
      down modulation of attentional guidance may represent effects that occur later in
      processing.

PMID- 15982131
TI  - 3-d interpolation in object perception: evidence from an objective performance
      paradigm.
AB  - Object perception requires interpolation processes that connect visible regions
      despite spatial gaps. Some research has suggested that interpolation may be a 3-D
      process, but objective performance data and evidence about the conditions leading
      to interpolation are needed. The authors developed an objective performance
      paradigm for testing 3-D interpolation and tested a new theory of 3-D contour
      interpolation, termed 3-D relatability. The theory indicates for a given edge
      which orientations and positions of other edges in space may be connected to it
      by interpolation. Results of 5 experiments showed that processing of orientation
      relations in 3-D relatable displays was superior to processing in 3-D
      nonrelatable displays and that these effects depended on object formation. 3-D
      interpolation and 3-D relatabilty are discussed in terms of their implications
      for computational and neural models of object perception, which have typically
      been based on 2-D-orientation-sensitive units.

PMID- 15982132
TI  - Toward an appropriate baseline for measures of eye movement behavior during
      reading.
AB  - In empirical studies of human eye movement behavior during reading, it is common
      to compute various summary measures from the data, but these measures are
      typically not evaluated with respect to corresponding measures of baseline
      performance. The authors present a method for deriving an appropriate baseline by
      mapping the actual behavior to a random perturbation of the text being read, and
      they find surprising similarities between the baseline and the empirical data.
      The practical message from these findings is that the importance of a particular
      factor in explaining either empirical or simulated eye movement patterns should
      be evaluated using an appropriate baseline. In addition to this methodological
      point, the authors suggest that eye movement behavior in reading may be
      constrained by the properties of an eye-guidance system that has adapted to the
      coarse-grained statistical properties of written language.

PMID- 15982133
TI  - Look here but ignore what you see: effects of distractors at fixation.
AB  - Distractor interference effects were compared between distractors in the
      periphery and those placed at fixation. In 6 experiments, the authors show that
      fixation distractors produce larger interference effects than peripheral
      distractors. However, the fixation distractor effects are modulated by perceptual
      load to the same extent as are peripheral distractor effects (Experiments 1 and
      2). Experiment 3 showed that fixation distractors are harder to filter out than
      peripheral distractors. The larger distractor effects at fixation are not due to
      the cortical magnification of foveal stimuli (Experiments 4 and 5), nor can they
      be attributed to cuing by the fixation point (Experiment 2), the lower
      predictability or greater location certainty of fixation distractors (Experiment
      5), or their being in a central position (Experiment 6). The authors suggest that
      preferential access to attention renders fixation distractors harder to ignore
      than peripheral distractors.

PMID- 15982134
TI  - Speeded classification in a probabilistic category structure: contrasting
      exemplar-retrieval, decision-boundary, and prototype models.
AB  - Speeded perceptual classification experiments were conducted to distinguish among
      the predictions of exemplar-retrieval, decision-boundary, and prototype models.
      The key manipulation was that across conditions, individual stimuli received
      either probabilistic or deterministic category feedback. Regardless of the
      probabilistic feedback, however, an ideal observer would always classify the
      stimuli by using an identical linear decision boundary. Subjects classified the
      probabilistic stimuli with lower accuracy and longer response times than they
      classified the deterministic stimuli. These results are in accord with the
      predictions of the exemplar model and challenge the predictions of the prototype
      and decision-boundary models.

PMID- 15982135
TI  - Optical trajectories and the informational basis of fly ball catching.
AB  - D. M. Shaffer and M. K. McBeath (see record 2002-02027-006) plotted the optical
      trajectories of uncatchable fly balls and concluded that linear optical
      trajectory is the informational basis of the actions taken to catch these balls.
      P. McLeod, N. Reed, and Z. Dienes (see record 2002-11140-016) replotted these
      trajectories in terms of changes in the tangent of optical angle over time and
      concluded that optical acceleration is the informational basis of fielder
      actions. Neither of these conclusions is warranted, however, because the optical
      trajectories of even uncatchable balls confound the information that is the basis
      of fielder action with the effects of those same actions on these trajectories.
      To determine the informational basis of fielder action, it is necessary to do the
      control-theory-based Test for the Controlled Variable, in which the informational
      basis of catching is found by looking for features of optical trajectories that
      are protected from experimentally or naturally applied disturbances.

PMID- 15982136
TI  - Mediators, moderators, and predictors of 1-year outcomes among children treated
      for early-onset conduct problems: a latent growth curve analysis.
AB  - Several child conduct problem interventions have been classified as either
      efficacious or well established. Nevertheless, much remains to be learned about
      predictors of treatment response and mechanisms of behavioral change. In this
      study, the authors combine data from 6 randomized clinical trials and 514
      children, ages 3.0-8.5 years, to evaluate moderators, mediators, and predictors
      of outcome. Among other findings, latent growth curve models of mother-report and
      observational measures of child externalizing behaviors suggested that marital
      adjustment, maternal depression, paternal substance abuse, and child comorbid
      anxiety/depression each moderated treatment response. Moreover, critical, harsh,
      and ineffective parenting both predicted and mediated outcome, with the most
      favorable responses observed when parents scored relatively low on each construct
      at intake yet improved during treatment. Implications for treatment nonresponders
      are discussed.

PMID- 15982137
TI  - Predicting future antisocial personality disorder in males from a clinical
      assessment in childhood.
AB  - It is essential to identify childhood predictors of adult antisocial personality
      disorder (APD) to target early prevention. It has variously been hypothesized
      that APD is predicted by childhood conduct disorder (CD), attention
      deficit/hyperactivity disorder (ADHD), or both disorders. To test these competing
      hypotheses, the authors used data from a single childhood diagnostic assessment
      of 163 clinic-referred boys to predict future APD during early adulthood.
      Childhood Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.;
      American Psychiatric Association, 1987) CD, but not ADHD, significantly predicted
      the boys' subsequent APD. An interaction between socioeconomic status (SES) and
      CD indicated that CD predicted APD only in lower SES families, however. Among
      children who met criteria for CD, their number of covert but not overt CD
      symptoms improved prediction of future APD, controlling for SES.

PMID- 15982138
TI  - Disentangling the underlying dimensions of psychopathy and conduct problems in
      childhood: a community study.
AB  - The psychometric and predictive validity of callous-unemotional (CU) traits as an
      early precursor of conduct disorder and antisocial behavior were assessed. A
      community sample of children (4-9 years of age) were tested 12 months apart with
      the Antisocial Process Screening Device (APSD; P. J. Frick & R. D. Hare, 2002), a
      measure of early signs of psychopathy in children. Factor analysis supported the
      structure of the APSD. Given controversy surrounding construct overlap between
      psychopathy and conduct problems, a factor analysis was conducted on pooled items
      from the Strengths and Difficulties Questionnaire and APSD. A 5-factor solution
      resulted: antisocial, hyperactivity, CU traits, anxiety, and peer problems. CU
      traits added small but significant improvements in the 12-month prediction of
      antisocial behavior for boys and older girls, after controlling for Time 1
      measures. These results indicate that although the dimensions of the APSD overlap
      with dimensions of the disruptive behavior disorders, CU traits have unique
      predictive validity in childhood.

PMID- 15982139
TI  - What aspects of peer relationships are impaired in children with attention
      deficit/hyperactivity disorder?
AB  - Participants included 165 children with attention-deficit/hyperactivity disorder
      (ADHD; 130 boys, 35 girls) and their 1,298 same-sex classmates (1,026 boys, 272
      girls) who served as raters. For each child with ADHD, a child of the same sex
      was randomly selected from the same classroom to serve as a comparison child,
      which yielded 165 dyads. Consistent with predictions, contrasted with the
      comparison children, those with ADHD were lower on social preference, higher on
      social impact, less well liked, and more often in the rejected social status
      category; they also had fewer dyadic friends. When liking ratings that children
      made versus received were examined, children with ADHD had less positive
      imbalance and greater negative imbalance relative to comparison children.
      Analyses that considered the types of peers who chose children with ADHD as
      friends or nonfriends demonstrated that children with ADHD were nominated as
      nonfriends by children of higher social preference and who were better liked by
      others.

PMID- 15982140
TI  - The role of children's ethnicity in the relationship between teacher ratings of
      attention-deficit/hyperactivity disorder and observed classroom behavior.
AB  - Significant ethnic differences have been consistently documented on attention
      deficit/hyperactivity disorder (ADHD) teacher rating scales. Whether these ethnic
      differences result from a teacher rating bias or reflect actual classroom
      behavior patterns is unknown. Ethnic differences between Caucasian and African
      American (AA) elementary schoolchildren on teacher ratings and codings of
      observed classroom behavior were examined with latent variables. In structural
      equation models, correlations between teacher ratings and observed classroom
      behavior suggested nonbiased teacher ratings of AA schoolchildren with diagnosed
      ADHD. Ethnic differences were documented for both teacher ratings of ADHD and
      classroom behavior. Differences in classroom behavior were attenuated when the
      behavior of an average child in the classroom was taken into account. Multiple
      explanations for this pattern of results are discussed.

PMID- 15982141
TI  - Parent and partner violence in families with young children: rates, patterns, and
      connections.
AB  - In this study, the authors assessed men's and women's partner and parent physical
      aggression among 453 representatively sampled families with young children. The
      prevalences of partner aggression and of severe parent aggression were higher
      than previously reported. Substantial rates of co-occurrence were found. Risk
      ratios and regression analyses indicated that connections between (a) husbands'
      and wives' partner aggression and (b) mothers' and fathers' parent aggression
      were especially strong. Patterns of co-occurrence pointed to the probable
      relative importance of family-level, in comparison with individual, predictors of
      aggression. Patterns of co-occurring violence are described in light of the
      theoretical literature. Implications for studying family violence in community
      samples are discussed.

PMID- 15982142
TI  - Long-term follow-up to a randomized clinical trial of multisystemic therapy with
      serious and violent juvenile offenders.
AB  - In this study, the authors examined the long-term criminal activity of 176 youths
      who had participated in either multisystemic therapy (MST) or individual therapy
      (IT) in a randomized clinical trial (C. M. Borduin et al., 1995). Arrest and
      incarceration data were obtained on average 13.7 (range = 10.2-15.9) years later
      when participants were on average 28.8 years old. Results show that MST
      participants had significantly lower recidivism rates at follow-up than did their
      counterparts who participated in IT (50% vs. 81%, respectively). Moreover, MST
      participants had 54% fewer arrests and 57% fewer days of confinement in adult
      detention facilities. This investigation represents the longest follow-up to date
      of a MST clinical trial and suggests that MST is relatively effective in reducing
      criminal activity among serious and violent juvenile offenders.

PMID- 15982143
TI  - Using a five-factor lens to explore the relation between personality traits and
      violence in psychiatric patients.
AB  - Recent work suggests that predictors of violence are similar for individuals with
      and without mental illness. Although psychopathy is among the most potent of such
      predictors, the nature of its relation to violence is unclear. On the basis of a
      sample of 769 civil psychiatric patients, the authors explore the possibility
      that measures of psychopathy provide a glimpse of higher order personality traits
      that predispose individuals toward violence. Results indicate that general traits
      captured by a measure of the 5-factor model, particularly antagonism, were
      relatively strongly associated with violence and shared most of their violence
      relevant variance with a leading measure of psychopathy. Because interpersonal
      and affective features of psychopathy are less important than basic traits of
      antagonism in postdicting violence, it may be appropriate to broaden focus in
      risk assessment to patients' basic personality traits.

PMID- 15982144
TI  - Testing a four-factor model of psychopathy and its association with ethnicity,
      gender, intelligence, and violence.
AB  - Although a 2-factor model has advanced research on the psychopathy construct, a 3
      factor model was recently developed that emphasized pathological personality and
      eliminated antisocial behavior. However, dropping antisocial behavior from the
      psychopathy construct may not be advantageous. Using a large sample of
      psychiatric patients from the MacArthur Risk Assessment Study (J. Monahan & H. J.
      Steadman, 1994), the authors used confirmatory factor analysis to test a 4-factor
      model of psychopathy, which included interpersonal, affective, and behavioral
      impulsivity dimensions and an antisocial behavior dimension. Model fit was good
      for this 4-factor model, even when ethnicity, gender, and intelligence variables
      were included in the model. Structural equation modeling was used to compare the
      3- and 4-factor models in predicting proximal (violence) and distal
      (intelligence) correlates of psychopathy.

PMID- 15982145
TI  - Victimization over the life span: a comparison of lesbian, gay, bisexual, and
      heterosexual siblings.
AB  - Lifetime victimization was examined in a primarily European American sample that
      comprised 557 lesbian/gay, 163 bisexual, and 525 heterosexual adults. Lesbian,
      gay, and bisexual (LGB) participants were recruited via LGB e-mail lists,
      periodicals, and organizations; these participants recruited 1 or more siblings
      for participation in the study (81% heterosexual, 19% LGB). In hierarchical
      linear modeling analyses, sexual orientation was a significant predictor of most
      of the victimization variables. Compared with heterosexual participants, LGB
      participants reported more childhood psychological and physical abuse by parents
      or caretakers, more childhood sexual abuse, more partner psychological and
      physical victimization in adulthood, and more sexual assault experiences in
      adulthood. Sexual orientation differences in sexual victimization were greater
      among men than among women.

PMID- 15982146
TI  - Prevention and early intervention of anxiety disorders in inhibited preschool
      children.
AB  - This article reports results from an early intervention program aimed at
      preventing the development of anxiety in preschool children. Children were
      selected if they exhibited a high number of withdrawn/inhibited behaviors--one of
      the best identified risk factors for later anxiety disorders--and were randomly
      allocated to either a 6-session parent-education program or no intervention. The
      education program was group based and especially brief to allow the potential for
      public health application. Children whose parents were allocated to the education
      condition showed a significantly greater decrease in anxiety diagnoses at 12
      months relative to those whose parents received no intervention. However, there
      were no significant effects demonstrated on measures of inhibition/withdrawal.
      The results demonstrate the value of (even brief) very early intervention for
      anxiety disorders, although these effects do not appear to be mediated through
      alterations of temperament.

PMID- 15982147
TI  - Therapist alliance-building behavior within a cognitive-behavioral treatment for
      anxiety in youth.
AB  - Explored the specific behavior of therapists contributing to a child client's
      perception of a therapeutic alliance with youth (n = 56) who received a
      manualized cognitive-behavioral treatment for anxiety disorders. The first 3
      sessions were coded for 11 therapist behaviors hypothesized to predict ratings of
      alliance. Child, therapist, and observer alliance ratings were gathered after the
      3rd and 7th therapy sessions. "Collaboration" positively predicted early child
      ratings of alliance, and "finding common ground" and "pushing the child to talk"
      negatively predicted early child ratings of alliance. Although no coded therapist
      behaviors predicted early therapist ratings of alliance, "collaboration" and "not
      being overly formal" positively predicted therapist alliance ratings by Session
      7. Child, observer, and therapist ratings of alliance were significantly
      correlated. Results are discussed with regard to the identified behavior of the
      therapist as a step toward the identification of empirically supported strategies
      for building a stronger child-therapist alliance.

PMID- 15982148
TI  - Physical, mental, and social catastrophic cognitions as prognostic factors in
      cognitive-behavioral and pharmacological treatments for panic disorder.
AB  - The authors explored the prognostic value of 3 different types of catastrophic
      cognitions in the treatment of panic disorder with and without mild-to-moderate
      agoraphobia using a sample of 143 participants who received either cognitive
      behavioral therapy (CBT) or imipramine in a randomized controlled trial. Stronger
      fears of social catastrophes both prior to and following treatment with CBT or
      imipramine were associated with a poorer outcome. In contrast, cognitions
      involving physical or mental catastrophes were unrelated to outcome, regardless
      of whether these thoughts were measured prior to or following treatment. These
      findings are consistent with the notion that although the intensity of physical
      catastrophe cognitions may best discriminate between panic disorder and other
      anxiety disorders, it is the intensity of social catastrophe cognitions that is
      most closely tied to success in treating this disorder.

PMID- 15982149
TI  - Randomized trial of cognitive-behavioral therapy for chronic posttraumatic stress
      disorder in adult female survivors of childhood sexual abuse.
AB  - The authors conducted a randomized clinical trial of individual psychotherapy for
      women with posttraumatic stress disorder (PTSD) related to childhood sexual abuse
      (n = 74), comparing cognitive-behavioral therapy (CBT) with a problem-solving
      therapy (present-centered therapy; PCT) and to a wait-list (WL). The authors
      hypothesized that CBT would be more effective than PCT and WL in decreasing PTSD
      and related symptoms. CBT participants were significantly more likely than PCT
      participants to no longer meet criteria for a PTSD diagnosis at follow-up
      assessments. CBT and PCT were superior to WL in decreasing PTSD symptoms and
      secondary measures. CBT had a significantly greater dropout rate than PCT and WL.
      Both CBT and PCT were associated with sustained symptom reduction in this sample.

PMID- 15982150
TI  - Individual behavioral profiles and predictors of treatment effectiveness for
      children with autism.
AB  - Differential responsiveness to intervention programs suggests the inadequacy of a
      single treatment approach for all children with autism. One method for reducing
      outcome variability is to identify participant characteristics associated with
      different outcomes for a specific intervention. In this investigation, an
      analysis of archival data yielded 2 distinct behavioral profiles for responders
      and nonresponders to a widely used behavioral intervention, pivotal response
      training (PRT). In a prospective study, these profiles were used to select 6
      children (3 predicted responders and 3 predicted nonresponders) who received PRT.
      Children with pretreatment responder profiles evidenced positive changes on a
      range of outcome variables. Children with pretreatment nonresponder profiles did
      not exhibit improvements. These results offer promise for the development of
      individualized treatment protocols for children with autism.

PMID- 15982151
TI  - Mental illness and/or mental health? Investigating axioms of the complete state
      model of health.
AB  - A continuous assessment and a categorical diagnosis of the presence (i.e.,
      flourishing) and the absence (i.e., languishing) of mental health were proposed
      and applied to the Midlife in the United States study data, a nationally
      representative sample of adults between the ages of 25 and 74 years (N = 3,032).
      Confirmatory factor analyses supported the hypothesis that measures of mental
      health (i.e., emotional, psychological, and social well-being) and mental illness
      (i.e., major depressive episode, generalized anxiety, panic disorder, and alcohol
      dependence) constitute separate correlated unipolar dimensions. The categorical
      diagnosis yielded an estimate of 18.0% flourishing and, when cross-tabulated with
      the mental disorders, an estimate of 16.6% with complete mental health.
      Completely mentally healthy adults reported the fewest health limitations of
      activities of daily living, the fewest missed days of work, the fewest half-day
      work cutbacks, and the healthiest psychosocial functioning (low helplessness,
      clear life goals, high resilience, and high intimacy).

PMID- 15982152
TI  - Further examination of the exposure model underlying the efficacy of written
      emotional disclosure.
AB  - In the current study, the authors examined the effects of systematically varying
      the writing instructions for the written emotional disclosure procedure. College
      undergraduates with a trauma history and at least moderate posttraumatic stress
      symptoms were asked to write about (a) the same traumatic experience, (b)
      different traumatic experiences, or (c) nontraumatic everyday events across 3
      written disclosure sessions. Results show that participants who wrote about the
      same traumatic experience reported significant reductions in psychological and
      physical symptoms at follow-up assessments compared with other participants.
      These findings suggest that written emotional disclosure may be most effective
      when individuals are instructed to write about the same traumatic or stressful
      event at each writing session, a finding consistent with exposure-based
      treatments.

PMID- 15982153
TI  - Multimodal homesickness prevention in boys spending 2 weeks at a residential
      summer camp.
AB  - Homesickness is the distress or impairment caused by an actual or anticipated
      separation from home. It is characterized by preoccupying thoughts of home and
      attachment objects. In its severe form, homesickness is subjectively distressing
      and has clinically significant cognitive, emotional, and behavioral sequelae.
      This study provided 75 boys who ranged in age from 8 to 16 years and who were 1st
      year campers at an overnight summer camp with an inexpensive, multimodal
      homesickness prevention package. Results suggest that combining environmental
      information, psychoeducation, social support, explicit coping instruction,
      caregiver education, practice time away from home, and surrogate caregiver
      training can reduce homesickness and associated behavior problems. These data
      support the theory that novelty reduction, attitudinal shifts, preseparation
      coping enhancement, and supportive social environments diminish the negative
      emotional intensity of homesickness.

PMID- 15982154
TI  - A longitudinal study of retirement in older male veterans.
AB  - In this study, the authors examined the effect of retirement on psychological and
      physical symptoms in 404 older male veterans who were taking part in an ongoing
      longitudinal study. Hierarchical linear modeling was used to analyze symptom
      trajectories from preretirement, peri-retirement, and postretirement periods in
      veterans with either lifetime full or partial posttraumatic stress disorder
      (PTSD), trauma exposure only, or no traumatic exposure. As expected, the PTSD
      group experienced greater increases in psychological and physical symptoms during
      retirement, relative to the other groups. Retirement due to poor health in the
      PTSD group did not account for the findings regarding physical symptoms. Results
      indicate that clinicians should recognize and address the potential for older
      individuals with PTSD to experience difficulties during retirement.

PMID- 15982156
TI  - Lack of interference in long-term memory for socially learned food preferences in
      rats (Rattus norvegicus).
AB  - Outside the laboratory, rats (Rattus norvegicus) are likely both to interact with
      several conspecifics that have eaten various foods and to eat a variety of foods
      themselves before they encounter any particular food for which they have a
      socially enhanced preference. Here the authors examine the stability of rats'
      socially learned food preferences following 6 days of potentially disruptive
      ingestive experiences. The authors found that 6 days of (a) eating unfamiliar
      foods, (b) interacting with demonstrators that had eaten unfamiliar foods, or (c)
      both eating unfamiliar foods and interacting with demonstrators that had eaten
      those foods had no measurable effect on rats' socially learned food preferences.
      The stability of socially enhanced food preferences over time and despite
      potentially disruptive experiences is consistent with the view that social
      learning about foods is an important determinant of the food choices of free
      living Norway rats.

PMID- 15982157
TI  - Human listeners are able to classify dog (Canis familiaris) barks recorded in
      different situations.
AB  - The authors investigated whether human listeners could categorize played-back dog
      (Canis familiaris) barks recorded in various situations and associate them with
      emotional ratings. Prerecorded barks of a Hungarian herding dog breed (Mudi)
      provided the sample. Human listeners were asked to rate emotionality of the
      vocalization and to categorize the situations on the basis of alternative
      situations provided on a questionnaire. The authors found almost no effect of
      previous experience with the given dog breed or of owning a dog. Listeners were
      able to categorize bark situations high above chance level. Emotionality ratings
      for particular bark samples correlated with peak and fundamental frequency and
      interbark intervals. The authors did not find a significant effect of tonality
      (harmonic-to-noise ratio) on either the emotionality rating or situation
      categorization of the human listeners. Humans' ability to recognize meaning
      suggests that barks could serve as an effective means of communication between
      dog and human.

PMID- 15982158
TI  - All great ape species follow gaze to distant locations and around barriers.
AB  - Following the gaze direction of conspecifics is an adaptive skill that enables
      individuals to obtain useful information about the location of food, predators,
      and group mates. In the current study, the authors compared the gaze-following
      skills of all 4 great ape species. In the 1st experiment, a human either looked
      to the ceiling or looked straight ahead. Individuals from all species reliably
      followed the human's gaze direction and sometimes even checked back when they
      found no target. In a 2nd experiment, the human looked behind some kind of
      barrier. Results showed that individuals from all species reliably put themselves
      in places from which they could see what the experimenter was looking at behind
      the barrier. These results support the hypothesis that great apes do not just
      orient to a target that another is oriented to, but they actually attempt to take
      the visual perspective of the other.

PMID- 15982159
TI  - A comparative analysis of global and local processing of hierarchical visual
      stimuli in young children (Homo sapiens) and monkeys (Cebus apella).
AB  - Results obtained with preschool children (Homo sapiens) were compared with
      results previously obtained from capuchin monkeys (Cebus apella) in matching-to
      sample tasks featuring hierarchical visual stimuli. In Experiment 1, monkeys, in
      contrast with children, showed an advantage in matching the stimuli on the basis
      of their local features. These results were replicated in a 2nd experiment in
      which control trials enabled the authors to rule out that children used spurious
      cues to solve the matching task. In a 3rd experiment featuring conditions in
      which the density of the stimuli was manipulated, monkeys' accuracy in the
      processing of the global shape of the stimuli was negatively affected by the
      separation of the local elements, whereas children's performance was robust
      across testing conditions. Children's response latencies revealed a global
      precedence in the 2nd and 3rd experiments. These results show differences in the
      processing of hierarchical stimuli by humans and monkeys that emerge early during
      childhood.

PMID- 15982160
TI  - Experience and materials affect combinatorial construction in tufted capuchin
      monkeys (Cebus apella).
AB  - Three movement procedures can combine nesting cups into seriated structures.
      Reliance on these procedures changes with age in human children, and the
      putatively most advanced emerges as a predominant procedure at 3 or more years.
      Six monkeys' (Cebus apella) combinatorial procedures and successes at nesting
      seriated cups were evaluated. The current study examined whether the procedures
      used (a) shift toward more efficient procedures after unguided experience, (b)
      are dependent on the type of object being combined, and (c) can be altered by
      specific training history. All factors produced a change in procedure for some
      individuals, suggesting that combinatorial procedure is a product of the dynamic
      influences of preexisting tendencies to act in certain ways, of environmental
      circumstances, and of prior experiences. Some monkeys preferred the putatively
      most cognitively complex procedure.

PMID- 15982161
TI  - A comparative study of the use of visual communicative signals in interactions
      between dogs (Canis familiaris) and humans and cats (Felis catus) and humans.
AB  - Dogs' (Canis familiaris) and cats' (Felis catus) interspecific communicative
      behavior toward humans was investigated. In Experiment 1, the ability of dogs and
      cats to use human pointing gestures in an object-choice task was compared using 4
      types of pointing cues differing in distance between the signaled object and the
      end of the fingertip and in visibility duration of the given signal. Using these
      gestures, both dogs and cats were able to find the hidden food; there was no
      significant difference in their performance. In Experiment 2, the hidden food was
      made inaccessible to the subjects to determine whether they could indicate the
      place of the hidden food to a naive owner. Cats lacked some components of
      attention-getting behavior compared with dogs. The results suggest that
      individual familiarization with pointing gestures ensures high-level performance
      in the presence of such gestures; however, species-specific differences could
      cause differences in signaling toward the human.

PMID- 15982162
TI  - Cache decision making: the effects of competition on cache decisions in Merriam's
      kangaroo rat (Dipodomys merriami).
AB  - Caching food is an economic, decision-making process that requires animals to
      take many factors into account, including the risk of pilferage. However, little
      is known about how food-storing animals determine the risk of pilferage. In this
      study, the authors examined the effect of a dominant competitor species on the
      caching and behavior of Merriam's kangaroo rat (Dipodomys merriami). The authors
      found that, as with conspecific competitors, kangaroo rats did not alter caching
      in response to the mere presence of a heterospecific competitor, but moved caches
      to an unpreferred area when the competitor's presence was paired with pilferage.
      These data suggest that Merriam's kangaroo rat assesses pilfer risk from actual
      pilferage by a competitor and adaptively alters cache strategy to minimize future
      risk.

PMID- 15982163
TI  - Number comprehension by a grey parrot (Psittacus erithacus), including a zero
      like concept.
AB  - A Grey parrot (Psittacus erithacus) that was able to quantify 6 item sets
      (including subsets of heterogeneous groups, e.g., blue blocks within groupings of
      blue and green blocks and balls) using English labels (I. M. Pepperberg, 1994a)
      was tested on comprehension of these labels, which is crucial for numerical
      competence (K. C. Fuson, 1988; see also record 1987-98811-000). He was, without
      training, asked "What color/object [number]?" for collections of various
      simultaneously presented quantities (e.g., subsets of 4, 5, and 6 blocks of 3
      different colors; subsets of 2, 4, and 6 keys, corks, and sticks). Accuracy was
      greater than 80% and was unaffected by array quantity, mass, or contour. His
      results demonstrated numerical comprehension competence comparable to that of
      chimpanzees and very young children. He also demonstrated knowledge of absence of
      quantity, using "none" to designate zero.

PMID- 15982164
TI  - Choosing and using tools: capuchins (Cebus apella) use a different metric than
      tamarins (Saguinus oedipus).
AB  - Cotton-top tamarins (Saguinus oedipus) selected canes positioned so that a
      straight inward pull brought food within reach (M. D. Hauser, 1997; see also
      record 1997-41347-003). Tamarins failed to retrieve food with canes in other
      positions, and they did not reposition these canes. In this study, tufted
      capuchin monkeys (Cebus apella) preferred canes they could pull straight in when
      these were present, but they also repositioned canes in individually variable
      ways, and their success at obtaining food with repositioned canes improved with
      practice. In accord with predictions drawn from ecological psychology, capuchins
      discovered affordances of canes through exploratory actions with these objects,
      whereas tamarins did not. Ecological theory predicts these differences on the
      basis of species-typical manipulative activity, and it provides a useful approach
      for the study of species differences in tool-using behavior.

PMID- 15982165
TI  - Socially meaningful vocal plasticity in adult Campbell's monkeys (Cercopithecus
      campbelli).
AB  - Campbell's monkeys (Cercopithecus campbelli) frequently exchange vocalizations,
      the combined-harmonic calls, with individuals responding to one another's calls.
      Previous work has shown that these calls can be grouped into several structural
      variants. Adult females differ in their variant repertoires, which may change
      during their adult life, particularly after changes in the group composition.
      Playback of females' currently produced variants triggered vocal responses from
      other group members, whereas the same females' former, no longer used variants
      and those of stranger females never did. In contrast, former variants caused long
      term cessation of vocal behavior, whereas stranger variants had no effect. Data
      showed that monkeys were able to distinguish between the different types of
      variants, indicating that these calls form part of a long-term social memory.

PMID- 15982166
TI  - Early experience and postembryonic maturation of body patterns in cuttlefish
      (Sepia officinalis).
AB  - This study investigates effects of the environment on the maturation of body
      patterns in cuttlefish (Sepia officinalis). Cuttlefish were reared either
      individually on a uniform background, which the authors have termed uniform
      solitary conditions (Group A), or grouped on variegated backgrounds, which the
      authors have termed varied-social conditions (Group B). At Days 1, 15, 30, and
      60, juveniles were placed individually in perceptually different testing
      conditions, either on small, variegated stones or on a uniform pale gray
      background. During development in both testing conditions, juveniles from Group B
      concealed themselves differently from those from Group A. Thus, it appears that
      the response to the background is subject to individual experience. Some
      hypotheses are discussed relating to the effect of early experience on the
      maturation of body patterns.

PMID- 15982167
TI  - Sex differences in righting from supine to prone in rats (Rattus norvegicus): a
      masculinized skeletomusculature is not required.
AB  - Previous research has shown that sex differences exist in the composition of
      lateral movements (E. F. Field, I. Q. Whishaw, & S. M. Pellis, 1996, 1997a,
      1997b; see also records 1996-06132-009, 1997-05322-015, and 1997-04722-005). An
      unresolved question is whether sex differences are present in other movements,
      such as rotation around the longitudinal axis, and whether this difference is
      dependent on a feminine or masculine skeletomusculature. Female rats (Rattus
      norvegicus) first rotate their forequarters and then their hindquarters in the
      same direction. Male rats exhibit rotation of the hindquarters counter to the
      direction of forequarter rotation. Males with the testicular feminized mutation,
      who have a feminized skeletomusculature and masculinized central nervous system,
      are similar to male controls. This study provides evidence that sex differences
      in movement integration are not restricted to the lateral plane, are not solely
      due to sex differences in skeletomusculature, and thus are likely mediated by the
      central nervous system.

PMID- 15982168
TI  - Research capacity building: a true action agenda.

PMID- 15982169
TI  - The L test of functional mobility: measurement properties of a modified version
      of the timed "up & go" test designed for people with lower-limb amputations.
AB  - BACKGROUND AND PURPOSE: Walk tests provide essential outcome information when
      assessing ambulation of individuals with lower-limb amputation and a prosthetic
      device. Existing tests have limitations such as ceiling effects or insufficient
      challenge. The objective of this study was to assess the reliability and validity
      of data for a clinical measure of basic mobility, the L Test of Functional
      Mobility (L Test). SUBJECTS: For this methodological study, 93 people with
      unilateral amputations (74% transtibial, 26% transfemoral; 78% male, 22% female;
      mean age=55.9 years) were consecutively recruited from an outpatient clinic.
      Twenty-seven subjects returned for retesting. METHODS: To assess concurrent
      validity, subjects completed the L Test, Timed "Up & Go" Test (TUG), 10-Meter
      Walk Test, and 2-Minute Walk Test, followed by the Activities-specific Balance
      Confidence scale, Frenchay Activities Index (FAI), and mobility subscale of the
      Prosthetic Evaluation Questionnaire (PEQ-MS). Amputation cause and level, walking
      aid use, automatic stepping, and age variables were used to assess discriminant
      validity. RESULTS: Intraclass correlation coefficients were .96 for interrater
      reliability and .97 for intrarater reliability, and minimal bias existed upon
      retesting. The magnitude of concurrent validity correlations (r) was very high
      between the L Test data and data for other walk tests and fair to moderate
      between the L Test data and data for self-report measures. The L Test
      discriminated between all groups as hypothesized. DISCUSSION AND CONCLUSION: The
      L Test is a 20-m test of basic mobility skills that includes 2 transfers and 4
      turns. It demonstrated excellent measurement properties in this study.

PMID- 15982170
TI  - Correlation of 3-dimensional shoulder kinematics to function in subjects with
      idiopathic loss of shoulder range of motion.
AB  - BACKGROUND AND PURPOSE: People with idiopathic loss of shoulder range of motion
      (ROM) have difficulty completing activities of daily living. This investigation
      was performed to determine the association between active glenohumeral ROM and
      function and to develop a multiple regression equation to explain variation in
      function in people with idiopathic loss of shoulder motion. SUBJECTS AND METHODS:
      This was a comparative study of 21 subjects (18 female, 3 male), using
      measurements of shoulder kinematics and administration of the Shoulder Rating
      Questionnaire (SRQ). Electromagnetic tracking sensors monitored the 3-dimensional
      position of the scapula and humerus throughout active shoulder motions.
      Correlations were performed between the active ROMs of interest and various
      demographic factors and the SRQ. A multiple regression equation was generated.
      RESULTS: A multiple regression equation including scapular-plane abduction,
      external rotation at the side, external rotation at 90 degrees of abduction, and
      weight explained 69% of the variation in the SRQ scores. DISCUSSION AND
      CONCLUSION: The results suggest that active ROM can be used to predict function
      in people with idiopathic loss of shoulder ROM.

PMID- 15982171
TI  - Incidence of and risk factors for falls following hip fracture in community
      dwelling older adults.
AB  - BACKGROUND AND PURPOSE: Hip fracture is a major medical problem among older
      adults, leading to impaired balance and gait and loss of functional independence.
      The purpose of this study was to determine the incidence of and risk factors for
      falls 6 months following hospital discharge for a fall-related hip fracture in
      older adults. SUBJECTS: Ninety of 100 community-dwelling older adults (> or =65
      years of age) hospitalized for a fall-related hip fracture provided data for this
      study. METHODS: An observational cohort study used interviews and medical records
      to obtain information on demographics, prefracture health, falls, and functional
      status. Self-report of falls and performance-based measures of balance and
      mobility were completed 6 months after discharge. RESULTS: A total of 53.3% of
      patients (48/90) reported 1 or more falls in the 6 months after hospitalization.
      Older adults who fell following discharge had greater declines in independence in
      activities of daily living and lower performance on balance and mobility
      measures. Prefracture fall history and use of a gait device predicted
      postdischarge falls. DISCUSSION AND CONCLUSION: Falls following hip fracture can
      be predicted by premorbid functional status.

PMID- 15982172
TI  - Navicular drop measurement in people with rheumatoid arthritis: interrater and
      intrarater reliability.
AB  - BACKGROUND AND PURPOSE: Navicular drop (ND) measurement may be a valuable
      examination technique for patients with rheumatoid arthritis (RA). However, no
      data exist on reliability for this technique in patients with RA. The purposes of
      this study were: (1) to determine interrater and intrarater reliability of ND
      measurements in people with RA, (2) to compare ND values of people with RA with
      published normative data, and (3) to investigate ND measurement error associated
      with the use of skin markings. SUBJECTS: Ten women (20 feet) with RA consented to
      participate. METHODS: Patients completed demographic and function questionnaires.
      Navicular height (NH) measurements were taken by 2 physical therapists and 1
      physical therapist student, following four 1-hour training sessions, using
      standardized methods and a digital height gauge. Four different NH measurements
      were taken 3 times on each foot by each of the 3 examiners during a morning
      session and then repeated during an afternoon session on the same day. Navicular
      drop values were calculated, including ND1 (as reported in the literature), ND2
      (compensating for skin error), and ND3 (single-limb stance). Intraclass
      correlation coefficients (ICCs) and standard errors of measurement (SEMs) were
      used to establish reliability. RESULTS: Means (+/-SD) for each ND measure for
      sessions 1 and 2, respectively, were as follows: ND1=8.36+/-5.29 mm and 8.29+/
      5.24 mm, ND2=9.95+/-5.44 mm and 9.57+/-5.37 mm. The ICCs (2,1 and 2,k,
      respectively) for all interrater measurements ranged from .67 to .92 (SEM=2.0-3.3
      mm) and from .85 to .97 (SEM=1.1-2.0 mm). The ICCs (2,1 and 2,k, respectively)
      for intrarater measurements ranged from .73 to .95 (SEM=1.3-2.8 mm) and from .90
      to .98 (SEM=0.7-1.6 mm). Paired t tests showed the means of ND1 and ND2 for each
      examiner and for both sessions were significantly different. DISCUSSION AND
      CONCLUSION: The results suggest that ND measurements for people with RA can be
      taken reliably by clinicians with varied experience. The ND values for our
      subjects were slightly greater than reported normal values of 6 to 8 mm. Error
      associated with skin markings was statistically significant for all sessions and
      examiners.

PMID- 15982173
TI  - Physical therapist management of an adult with osteochondritis dissecans of the
      knee.
AB  - BACKGROUND AND PURPOSE: Osteochondritis dissecans (OCD) primarily occurs between
      10 and 20 years of age. Adult patients (>20 years) tend to respond poorly to
      nonsurgical management. This case report describes the physical therapist
      management of an adult with OCD at the tibiofemoral joint. CASE DESCRIPTION: A 24
      year-old woman had insidious onset of right knee pain. Magnetic resonance imaging
      confirmed the diagnosis of OCD. Interventions included iontophoresis,
      strengthening exercises, and instruction in strategies to minimize loading across
      the knee. OUTCOME: The patient received 5 intervention sessions. At discharge and
      9-month follow-up, she reported 95% function (Single Assessment Numeric
      Evaluation) and no pain while performing full work duties. DISCUSSION: This case
      illustrates the process, including the use of evidence, of making clinical
      decisions about the physical therapist management of an adult with OCD.

PMID- 15982174
TI  - Exercise prescription for a patient 3 months after hip fracture.
AB  - BACKGROUND AND PURPOSE: Most patients with hip fracture do not return to
      prefracture functional status 1 year after surgery. The literature describing
      interventions, however, does not use classic overload and specificity principles.
      The purpose of this case report is to describe the use of resistance training to
      improve functional outcomes in a patient following hip fracture. CASE
      DESCRIPTION: The patient was a 68-year-old woman who had a comminuted
      intertrochanteric fracture of the left hip 3 months previously. She used a cane
      for ambulation, and her walking was limited. The patient received 16 sessions of
      lower-extremity strengthening exercises, aerobic training on a stationary
      bicycle, functional training supervised by a physical therapist, and a home
      stretching program. OUTCOME: The patient's isometric muscle force for involved
      hip extension, hip abduction, and knee extension improved by 86%, 138%, and 33%,
      respectively; walking endurance increased by 22.5%; balance improved by 400%;
      balance confidence increased by 41%; and self-reported ability to perform lower
      extremity functional activities increased by 20%. DISCUSSION: The authors believe
      that some patients can perform comprehensive exercise programs after hip fracture
      and that properly designed programs can affect patient outcomes beyond observed
      impairments.

PMID- 15982175
TI  - Changing with the times.

PMID- 15982176
TI  - Provocation tests in functional gastrointestinal diseases: mechanistic diagnosis
      and therapeutic intervention.

PMID- 15982177
TI  - Has the identification of rectal hypersensitivity any implication in the clinical
      outcome of irritable bowel syndrome?
AB  - BACKGROUND: Sixty percent of patients with irritable bowel disease (IBS) are
      hypersensitive to rectal distension. It is uncertain to what extend the
      identification of this abnormality has an impact in the clinical outcome.
      OBJECTIVE: to evaluate if rectal hypersensitivity is associated with a different
      clinical outcome, prognosis and use of medical resources. MATERIAL AND METHODS:
      Patients with IBS (Rome II criteria) who underwent a rectal distension study at
      least one year before were eligible if they have not been included in any
      research protocol since then. We reviewed how many times in the last year they
      came to emergency room, underwent an endoscopy, and consulted a
      gastroenterologist or other medical physician for any reason. Also, a telephone
      interview was done by a gastroenterology fellow using a structured questionnaire
      to evaluate the frequency and severity of their symptoms in the last year and
      last month. RESULTS: A total of 52 patients were eligible and 38 were included.
      Fourteen were not included because inability to made a phone contact or did not
      consent to phone interview. Twenty six patients were hypersensitive and 12
      normosensitive. Both groups had similar symptoms (frequency and severity) but
      hypersensitive patients visited less to the gastroenterologist (1.2 +/- 0.2 vs.
      2.9 +/- 0.6 times yearly, p < 0.01). CONCLUSION: Identification of rectal
      hypersensitivity to distension is associated to less consultation to
      gastroenterologist, although severity and frequency of symptoms are not modified.
      Finding of an objective explanation of the symptoms seems to help patients to
      understand their disease, leading to a decrease in resources use.

PMID- 15982178
TI  - Eosinophilic esophagitis in adults, an emerging cause of dysphagia. Description
      of 9 cases.
AB  - BACKGROUND: Eosinophilic esophagitis is a rare condition mainly affecting
      children, although the number of cases reported in adults is on the increase. It
      is characterized by intense infiltration of eosinophilic leukocytes in the
      esophageal mucosa, without involvement of other sections of the alimentary canal.
      MATERIAL AND METHODS: Over the past year, following the performance of
      endoscopies and biopsies, our service identified nine patients who were diagnosed
      with suffering from this disorder. Each patient sought medical help for episodes
      of long-term, self-limited dysphagia or food impaction in the alimentary canal.
      RESULTS: Endoscopy revealed esophageal stenosis in the form of simultaneous
      contraction rings or regular stenosis. In six cases, the manometric study showed
      a nonspecific motor disorder of severe intensity affecting the esophageal body,
      and another patient had a disorder characterized by the presence of simultaneous
      waves and secondary peristaltic waves in the three thirds of the organ. These
      disorders are presumably due to eosinophilic infiltration of the muscular layer
      or ganglionar cells of the esophagus, and account for symptoms in these patients.
      Although the etiopathogenesis of this illness is uncertain, it is clearly an
      immunoallergic manifestation. CONCLUSIONS: As the number of diagnosed cases is on
      the increase, eosinophilic esophagitis is in adults a specific entity within the
      differential diagnosis of dysphagia in young males with a history of allergies.
      Eosiniphilic esophagitis responds in a different number of ways to therapies
      used. We successfully used fluticasone propionate, a synthetic corticoid applied
      topically, which proved to be efficient in the treatment of this illness by
      acting on the pathophysiological basis of the process. It does not have any
      adverse effects, thus offering advantages over other therapies such as systematic
      corticoids or endoscopic dilations.

PMID- 15982179
TI  - Effects of all-trans retinoic acid on tumor recurrence and metastasis.
AB  - OBJECTIVE: All-trans-retinoic acid (ATRA) promotes cell differentiation. We have
      studied its effect on the local recurrence and metastatic spreading of an
      experimental rhabdomyosarcoma in rats. DESIGN: syngenic rhabdomyosarcoma cells
      (S4MH) were inoculated s.c. in male WAG/RijCrl rats. After 25 days tumors were
      excised and a 40% hepatectomy was performed for all animals. Ten days later the
      rats were sacrificed and a thorough necropsy was performed. The animals were
      randomly allocated to receive daily doses of ATRA (5 mg/kg, i.p.) or its solvent
      (Clinoleic/ethanol 90/10), starting three days before surgery until the end of
      the experiment. RESULTS: ATRA reduced the incidence of local recurrence from 70
      to 33% (p < 0.05), but the tumor size was not altered (1.8 vs. 2.0 cc). Regarding
      inguinal metastasis, there was a six-fold decrease (0.2 vs. 1.2 cc; p < 0.05) in
      mean tumor volume, although the rate of this proliferation increased sharply (86
      vs. 29%; p < 0.05) for treated animals. The volume of the retroperitoneal tumor
      masses also decreased with ATRA (0.7 vs. 5.1 cc; p < 0.05), but the difference in
      rate was not significant (71 vs. 67%). Lung metastases, which were present in
      100% of control animals, were found in only 33% of treated rats, while the mean
      number of metastatic foci dropped from 26.7 to 5.7 (p < 0.05). CONCLUSION:
      Protocols including retinoid administration prior to and following primary tumor
      excision could help in controlling both recurrence and metastatic progression in
      surgically treated rhabdomyosarcoma.

PMID- 15982180
TI  - Adherence to treatment in inflammatory bowel disease.
AB  - AIM: Adherence to therapy is important to ensure success. We wanted to explore
      this feature in patients with inflammatory bowel disease. PATIENTS AND METHODS:
      We explored adherence to treatment and its modifiers in 40 patients with
      inflammatory bowel disease using a battery of tests. RESULTS: A 67% of patients
      (95% CI: 51-81%) acknowledged a certain degree of involuntary nonadherence, and
      35% (95% CI: 20-51%) of voluntary nonadherence. Overall, 72% (95% CI: 56-85%) of
      patients had some form of nonadherence. An objective correlation of these self
      reported data was assessed by the determination of urine salicylate levels in the
      subset of patients treated with mesalazine or its derivatives (15 cases). Two of
      them (13%) had no detectable urinary drug levels, indicating complete
      nonadherence. Voluntary nonadherence was higher in patients with lower scores in
      the intestinal (p = 0.02) and social areas (p = 0.015) of IBDQ-32, as well as in
      those with less active Crohn s disease (p < 0.005), patients with high depression
      scores and high patient-physician discordance (p = 0.01), patients with long
      standing disease (p = 0.057), patients who considered themselves not to be well
      informed about the treatment they were getting (p = 0.04) or who trusted their
      attending physicians less (p = 0.03). CONCLUSIONS: Intentional nonadherence to
      therapy is prevalent among patients with inflammatory bowel disease. A correction
      of factors associated to poor adherence could lead to higher therapeutic success.

PMID- 15982181
TI  - Clinical evaluation of drug-induced hepatitis.
AB  - OBJECTIVE: To ascertain the epidemiological characteristics, clinical symptoms,
      and evolution of drug-induced hepatitis over the last 22 years. EXPERIMENTAL
      DESIGN AND SUBJECTS: An observational, retrospective study between 1982 and 1993,
      and prospective study between 1994 and 2003. All patients in our department
      diagnosed with having drug-induced hepatitis were studied analyzing
      epidemiological (age, sex, cases per year, hospitalization) and clinical features
      (previous liver disease, hepatic symptoms, laboratory results), and follow-up
      (complete recovery or chronicity). RESULTS: A total of 61 patients were diagnosed
      as having drug-induced hepatitis, 26 men and 35 women (57%), mean age 52.4 years
      +/- 17 years, of which 72.2% were older than 40 years. A total of 43% were
      admitted to hospital. In 87% of cases, two or more drugs were involved, the most
      frequent being antituberculosis (19 cases), psychotropic (26 cases), and non
      steroidal anti-inflammatory drugs (45 cases). Evolution showed that 94% of
      patients recovered after the withdrawal of suspected causal drugs. CONCLUSIONS:
      The incidence of drug-induced hepatitis is higher in patients over 40 years of
      age, it being more common in females. Non-steroidal anti-inflammatory,
      psychotropic, and anti-tuberculosis agents were the main drugs involved. Most
      patients made a complete recovery after withdrawal of the suspected causal drug.

PMID- 15982182
TI  - Non-HFE hemochromatosis.

PMID- 15982183
TI  - Liver metastases from uveal melanoma.

PMID- 15982184
TI  - [Me, the intruder].

PMID- 15982185
TI  - Cardiovascular bubble dynamics.
AB  - Gas bubbles can form in the cardiovascular system as a result of patho
      physiological conditions or can be intentionally introduced for diagnostic or
      therapeutic reasons. The dynamic behavior of these bubbles is caused by a variety
      of mechanisms, such as inertia, pressure, interfacial tension, viscosity, and
      gravity. We review recent advances in the fundamental mechanics and applications
      of cardiovascular bubbles, including air embolism, ultrasound contrast agents,
      targeted microbubbles for drug delivery and molecular imaging, cavitation-induced
      tissue erosion for ultrasonic surgery, microbubble-induced angiogenesis and
      arteriogenesis, and gas embolotherapy.

PMID- 15982186
TI  - Causal influence: advances in neurosignal analysis.
AB  - The analysis of multichannel recordings such as electroencephalography (EEG) and
      magnetoencephalography (MEG) is important both for basic brain research and for
      medical diagnosis and treatment. Multivariate linear regressive analysis such as
      the AutoRegressive (MAR) modeling is an effective means to characterize, with
      high spatial, temporal, and frequency resolution, functional relations within
      multichannel neuronal data. Recent advances in MAR modeling show promise for the
      analysis and visualization of large-scale network interactions, especially in the
      ability to assess their causal relations. This article provides a detailed review
      of the advances in the development and application of causal influence measures
      for analyzing neurosignal within the framework of the MAR spectral analysis.
      First, we outline mathematical formulations of the MAR model and its related
      estimation procedures, with emphasis on the development of causal influence
      measures for analyzing brain circuits. Second, we address the technical issues on
      the practical applications of the causal measures to the neurobiological data. Of
      particular interest is the recent development of adapting the MAR to analyze
      neural spike train data. Third, we present a variety of applications ranging from
      basic neuroscience research to clinical applications as well as functional
      neuroimaging. We finally conclude with a brief summary and discuss future
      research development in this field.

PMID- 15982187
TI  - Agonist-induced regulation of mitochondrial and endoplasmic reticulum motility.
AB  - Using fluorescently tagged markers for organelles in conjunction with confocal
      microscopy, we have studied the effects of agonist-induced Ca2+ signals on the
      motility of mitochondria and the ER (endoplasmic reticulum). We observed that the
      muscarinic agonist carbachol produced a rapid, simultaneous and reversible
      cessation of the movements of both organelles, which was dependent on a rise in
      cytosolic Ca2+. This rise in Ca2+ was shown to cause a fall in cellular ATP
      levels, and the effect of carbachol on organelle movement could be mimicked by
      depleting ATP with metabolic inhibitors in the absence of any such rise in Ca2+.
      However, a Ca2+-sensing process independent of ATP appears also to be involved,
      because we identified conditions where the ATP depletion was blocked (by
      inhibitors of the Ca2+ pumps), but the organelle movements still ceased following
      a rise in cytosolic Ca2+. We conclude that the co-ordinated cessation of
      mitochondria and ER motility is a process regulated by the cytosolic
      concentration of both Ca2+ and ATP, and that these two parameters are likely to
      synergize to regulate the localization of the two organelles, and to facilitate
      the transfer of Ca2+ between them.

PMID- 15982188
TI  - Efficient constitutive expression of Bacillus subtilis xylanase A in Escherichia
      coli DH5alpha under the control of the Bacillus BsXA promoter.
AB  - Xylanase A (XynA) is a class G/11 xylanase secreted by Bacillus subtilis. XynA
      was purified to homogeneity from B. subtilis strain 168 culture supernatants by
      ethanol precipitation and cation-exchange chromatography. The DNA fragment
      encoding the XynA together with the BsXA promoter region was amplified by PCR
      from B. subtilis 168 genomic DNA, and cloned into the plasmid pT7T3 to give the
      plasmid pT7BsXA. After transformation of Escherichia coli DH5alpha with pT7BsXA,
      a 19-fold increase in the levels of the secreted XynA was detected in the
      supernatant as compared with the B. subtilis culture. Correct post-translation
      modification of the recombinant protein was confirmed by N-terminal amino acid
      sequencing and MS analyses. The pH- and temperature-dependences of the native and
      recombinant proteins were identical, indicating that the pT7BsXA may be useful
      for the constitutive expression of heterologous protein in E. coli.

PMID- 15982189
TI  - N-Acetylcysteine ameliorates the late phase of liver ischaemia/reperfusion injury
      in the rabbit with hepatic steatosis.
AB  - Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury
      and, therefore, the aim of the present study was to evaluate the in vivo effect
      of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase
      of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits
      were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar
      liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group
      receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and
      during the 6 h reperfusion period. Systemic and hepatic haemodynamics were
      monitored continuously. ALT (alanine aminotransferase) activity and bile
      production were measured. NMR spectroscopy was used to analyse bile composition.
      Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of
      production of reactive oxygen and nitrogen species. Moderate centrilobular
      hepatic steatosis was demonstrated by histology. The results showed that NAC
      administration significantly improved portal flow, hepatic microcirculation, bile
      composition and bile flow after 5 h of reperfusion. NAC administration was also
      associated with less hepatocellular injury, as indicated by ALT serum activity,
      and decreased the oxidation of DHR to RH. In conclusion, NAC administration
      decreased the extent of I/R injury in the steatotic liver, particularly during
      the late phase of reperfusion.

PMID- 15982190
TI  - BGN16.3, a novel acidic beta-1,6-glucanase from mycoparasitic fungus Trichoderma
      harzianum CECT 2413.
AB  - A new component of the beta-1,6-glucanase (EC 3.2.1.75) multienzymatic complex
      secreted by Trichoderma harzianum has been identified and fully characterized.
      The protein, namely BGN16.3, is the third isozyme displaying endo-beta-1,6
      glucanase activity described up to now in T. harzianum CECT 2413. BGN16.3 is an
      acidic beta-1,6-glucanase that is specifically induced by the presence of fungal
      cell walls in T. harzianum growth media. The protein was purified to
      electrophoretical homogenity using its affinity to beta-1,6-glucan as first
      purification step, followed by chomatofocusing and gel filtration. BGN16.3 has a
      molecular mass of 46 kDa in SDS/PAGE and a pI of 4.5. The enzyme only showed
      activity against substrates with beta-1,6-glycosidic linkages, and it has an
      endohydrolytic mode of action as shown by HPLC analysis of the products of
      pustulan hydrolysis. The expression profile analysis of BGN16.3 showed a carbon
      source control of the accumulation of the enzyme, which is fast and strongly
      induced by fungal cell walls, a condition often regarded as mycoparasitic
      simulation. The likely involvement beta-1,6-glucanases in this process is
      discussed.

PMID- 15982191
TI  - The most effective prevention program.

PMID- 15982192
TI  - Home-based asthma self-management education for inner city children.
AB  - Optimal home self-management in young children with asthma includes accurate
      symptom identification followed by timely and appropriate treatment. The
      objective of this study was to evaluate a home-based asthma educational
      intervention targeting symptom identification for parents of children with
      asthma. Two hundred twenty-one children with asthma were enrolled into an ongoing
      home-based clinical trial and randomized into either a standard asthma education
      (SAE) or a symptom/nebulizer education intervention (SNEI). Data included home
      visit records and parent's self-report on questionnaires. Symptom identification
      and self-management skills significantly improved from preintervention to
      postintervention for parents in both groups with the exception of checking
      medications for expiration dates and the frequency of cleaning nebulizer device
      and equipment. However, significantly more parents of children in the SNEI group
      reported treating cough symptoms as compared with the SAE group (p = 0.05). Of
      concern is that only 38% of all parents reported having an asthma action plan in
      the home. A targeted home-based asthma education intervention can be effective
      for improving symptom identification and appropriate use of medications in
      children with asthma. Home asthma educational programs should address accurate
      symptom identification and a demonstration of asthma medication delivery devices.

PMID- 15982193
TI  - The role of "envisioning the future" in the development of resilience among at
      risk youth.
AB  - The objective was to explore the process by which adolescents develop resilience
      and change their risk behaviors despite multiple stressors in their environment.
      The design was exploratory using grounded theory to understand the process from
      the teens' perspectives. Semistructured interviews were conducted with 32
      individuals-28 adolescents (age range 16-21 years) and 4 adults (age range 32 and
      72)-on two occasions. The participants used the basic social process "envisioning
      the future" to become resilient and stop engaging in risk behaviors. Envisioning
      the future included two processes "feeling competent" and "elevating
      expectations" that were facilitated within the context of a relationship with a
      reliable, caring, and competent adult. Participants in this study became
      resilient despite environmental stressors by setting higher expectations for
      themselves and feeling self-confident. The findings of this study provide
      information regarding the specific behaviors that promote positive outcomes in at
      risk youth and suggest ways in which public health nurses can facilitate these
      behaviors in both the youth and their mentors.

PMID- 15982194
TI  - Health-promoting behaviors and psychosocial well-being of university students in
      Hong Kong.
AB  - The objective of this study was to examine health-promoting behaviors and
      psychosocial well-being of university students in Hong Kong. A cross-sectional
      study was conducted using convenience sample (n = 247) of students recruited at
      various locations on campus. The Chinese version of the Health Promotion
      Lifestyle Profile II (HPLP-II; S. Walker, K. Sechrist, & N. Pender, 1995) was
      given to students as a questionnaire. Relatively few university students had a
      sense of "health responsibility" (6.5-27.1%), engaged in any form of physical
      activity (31.2%), or exercised regularly (13.8%). Less than half ate fruits
      (35.2%) and vegetables (48.9%) every day. Positive personal growth was reported
      by 50.6% of the students; 42.5% used stress-management skills and 74.1% rated
      their interpersonal relationships as meaningful and fulfilling. Students' scores
      on the health responsibility, nutritional habits, spiritual growth, interpersonal
      relations, or stress-management subscales of the HPLP-II did not differ
      significantly by gender, but males scored better than females (p = 0.001) on the
      physical exercise subscale. This study provides information on gender differences
      and specific needs of students which can help university administrators,
      curriculum planners, and community health professionals design guidelines for
      structuring a healthier environment and developing health education programs that
      support healthy choices among university students.

PMID- 15982195
TI  - Korean male smokers' perceptions of tobacco control policies in the United
      States.
AB  - The purpose of this secondary data analysis is to report Korean male smokers'
      perceptions of tobacco control policies in the United States. Descriptive data
      from four focus groups held in New York City in 2003 are presented. Focus group
      interviews were used to collect data, and the two investigators independently
      analyzed all four recorded group sessions. Korean male immigrants living in New
      York City area were recruited, and 22 volunteered to participate. Exclusion
      criteria included immigration to the United States before age 12, no smoking
      history, and use of chemical substance other than tobacco. Korean men differed in
      perceptions of the policies based on smoking status and length of U.S. residency.
      Among current smokers, recent immigrants had difficulty understanding smoking
      restrictions, whereas longtime residents complained of price increases. Both
      groups suggested that policies target the tobacco industry and do not target
      smokers. In contrast, former smokers supported more regulation of public smoking
      and suggested use of more aggressive antismoking campaigns. Public policymakers
      should take into consideration cultural attitudes and beliefs about smoking
      behavior in the design and implementation of tobacco control policies that affect
      ethnic groups whose cultural and value orientations may differ from the
      mainstream.

PMID- 15982196
TI  - Actions and beliefs related to hepatitis B and influenza immunization among
      registered nurses in Texas.
AB  - Studies indicate that roughly half of health care workers are not immunized
      against hepatitis B and influenza. Findings from a survey of 1,000 registered
      nurses (RNs) conducted to analyze their beliefs and actions related to
      immunization recommendations are reported. Only 8% of the responding RNs chose
      not to receive vaccination against hepatitis B. The primary reasons that nurses
      declined hepatitis B vaccination were because they were not working in nursing or
      did not believe they were at risk of exposure. Similarly, 86% of the RNs reported
      they had ever received a flu shot, and 69% reported of being immunized during 2
      of the previous 4 years. Rationale for receiving immunization included belief in
      its effectiveness, belief that they were at risk of exposure, and that it was
      provided free of charge. Reasons for declining included concerns about side
      effects, lack of concern about getting the illness, and doubts about
      effectiveness. The nurses who responded to the survey appear to value
      immunizations and generally adhere to immunization recommendations. Further study
      needs to be conducted on related issues, including follow-up for assessment of
      long-term protection of hepatitis B immunization and adherence to guidelines for
      postexposure prophylaxis. Ongoing monitoring and further study of serious
      complications of hepatitis B immunizations are also needed.

PMID- 15982197
TI  - Self-reported napping and nocturnal sleep in Taiwanese elderly insomniacs.
AB  - Abstract The aim of this study was to investigate the relationships between self
      reported nocturnal sleep quality and napping patterns in elderly persons with
      insomnia and to compare the nocturnal sleep quality between napping and non
      napping groups. Convenience sampling was used to recruit 60 community-dwelling
      elderly residents of Taichung City, Taiwan (age range 60-83 years, mean 67.1
      years) who reported insomnia. All participants scored greater than 5 on the
      Pittsburgh Sleep Quality Index (PSQI) questionnaire. Napping prevalence,
      frequency, and duration were assessed by participant interview. Self-reported
      sleep quality, sleep latency, sleep duration, sleep efficiency, sleep
      disturbance, use of sleep medication, and daytime dysfunction were measured with
      the PSQI. Sixty-four percentage of participants (n = 38) reported napping. There
      were no age, gender, and ethnicity differences on napping patterns. Global sleep
      quality, sleep efficiency, and sleep disturbance were significantly associated
      with prevalence of napping (r = 0.24-0.26, p < 0.05). A significant correlation
      was also found between global sleep quality and nap duration (r = 0.31, p <
      0.05). Elders in the napping group reported better global sleep quality (t = 2.2,
      p < 0.05) and sleep efficiency (t = 2.1, p < 0.05) than those in the non-napping
      group. The findings suggest that there is no need for health care providers to
      restrict elderly insomniacs' daytime napping.

PMID- 15982198
TI  - Emergency preparedness and bioterrorism response: development of an educational
      program for public health personnel.
AB  - Public health departments are under increasing pressure to provide emergency
      preparedness and bioterrorism response education to public health personnel. The
      challenge that health departments face is to provide cost-efficient, timely
      education to a large number of multidisciplinary personnel. This article
      describes an innovative strategy for providing this education to public health
      personnel using the health department's intranet system. The intranet system
      provided confidential information specific to the staff role and allowed for
      concurrent access to the program by multiple individuals at different service
      sites. Knowledge acquisition was tested through short multiple-choice questions
      that followed the specific information modules. The intranet system faced a
      number of challenges during the pilot-testing phase, primarily related to changes
      in the role of the public health nurse and limitations in funding and public
      health staff to maintain and monitor the bioterrorism response program and the
      intranet system. The design of the program may prove useful for other public
      health organizations when a need exists for quick delivery of information to a
      large number of personnel. It may especially be useful in providing basic
      emergency preparedness and bioterrorism education to new personnel in health
      departments.

PMID- 15982199
TI  - Sustained nurse home visiting in early childhood: exploring Australian nursing
      competencies.
AB  - Abstract There is strong evidence that a comprehensive model of sustained nurse
      home visiting (SNHV) in early childhood can improve child and family outcomes for
      vulnerable and at-risk families. There is also evidence that nurse home visitors
      experience challenges in delivering SNHV. This article aims to identify the
      nursing competencies needed for delivering a comprehensive model of SNHV and
      highlight the areas where further competency development is required. Qualitative
      analysis compared the content and language of published registered generalist and
      child and family nursing competency statements for Australian nurses with the
      work experiences of a team of community-based nurses delivering SNHV. Development
      of competencies is needed in the areas of (a) enhanced knowledge of child
      development, social determinants of health, and broader outcomes for individuals
      and populations; (b) advanced skills in fine observation, anticipatory guidance,
      negotiating, modelling and experimentation, holistic case management, and working
      in interdisciplinary teams; and (c) attitudinal competency for working "with" and
      supporting risk taking. The current published competencies for general and child
      and family nurses do not encompass the different and advanced competencies
      required for performing SNHV. Competency development and associated nurse
      training and support are needed for delivery of quality SHNV services.

PMID- 15982200
TI  - Student nurses participate in public health research and practice through a
      school-based screening program.
AB  - Obesity has reached epidemic proportions among children in minority populations,
      placing them at risk for diabetes and hypertension. The importance of educating a
      generation of nurses who have the knowledge, skills, and passion to address this
      public health need is crucial to the profession and to America's health. This
      article describes the use of a Community Partnership Model to frame baccalaureate
      nursing students' (B.S.N.) service learning within the context of a research
      study to screen middle- and high-school students for health risks. The missions
      of education, research, and practice are linked together in the model by three
      processes: evidence-based practice, service learning, and scholarly teaching. The
      aim of the project was early identification of obesity, hypertension, and type 2
      diabetes and their predictors in a high-risk student population, between 12 and
      19 years of age. Early evidence indicates that the model is feasible and
      effective for directing student learning and addressing public health problems in
      the community.

PMID- 15982201
TI  - Changing times, changing needs, changing programs.1952.

PMID- 15982202
TI  - Pharmacological properties and clinical efficacy of a recently licensed systemic
      antifungal, caspofungin.
AB  - Caspofungin, a semisynthetic derivative of the pneumocandin B(0), is the first
      licensed compound of a new class of antifungal agents, the echinocandins. It
      attacks the fungal cell by selective inhibition of the beta-(1,3)-d-glucan
      synthase, which is not present in mammalian cells. In vitro studies have
      indicated a potent fungicidal effect on Candida species, and in vivo studies in
      immunocompromised animals with invasive candidiasis demonstrated a favourable
      outcome. In randomized clinical trials in patients with oropharyngeal/oesophageal
      and invasive candidiasis, caspofungin was at least as effective as amphotericin B
      deoxycholate, yet showed a significantly superior safety profile. Of patients
      with invasive aspergillosis refractory to or intolerant of other antifungal
      agents, 45% showed a partial or complete response to caspofungin given as a
      salvage treatment. Also, it demonstrated comparable clinical efficacy but
      superior tolerability in the empirical antifungal therapy in neutropenic patients
      compared with liposomal amphothericin B. Caspofungin has an excellent
      tolerability and a low potential for drug interactions. Thus, caspofungin
      represents an interesting and clinically valuable new antifungal drug that
      broadens the available therapeutic armamentarium for the treatment of invasive
      fungal infections.

PMID- 15982203
TI  - Primary frontal sinus aspergillosis: an uncommon occurrence.
AB  - Primary frontal sinus aspergillosis is extremely uncommon with only few cases
      reported in the English literature. Isolated frontal sinus aspergillosis is
      usually asymptomatic and produces symptoms due to orbital or intracranial
      involvement. We report two cases of primary frontal sinus aspergillosis,
      presenting as frontoethmoidal mucocele and mimicking a 'Pott's puffy tumor,'
      respectively. Forehead swelling produced by frontal sinus aspergillosis will be
      the first to be reported in the English literature.

PMID- 15982204
TI  - Two cases of cutaneous cryptococcosis.
AB  - We report two cases of cutaneous cryptococcosis in male patients without
      underlying disease. Case 1 had a granulomatous mass on his right neck, gradually
      enlarging for 3 months. After the mass was debrided surgically in a hospital, the
      incision wound gradually developed into a severe ulceration. Mycological
      examination revealed Cryptococcus neoformans infection. It was significant that
      histopathology of both pre-surgery granuloma and post-surgery ulceration revealed
      thick-walled spores with thick capsule. Chest X-ray revealed a shadow in the left
      lower lung. After treatment with amphotec for 21 days, the lesion healed. Case 2
      had an approximately 2 x 2 cm solitary dull nodule on his right thigh, which had
      been present for 8 months. Mycological examination confirmed that the lesion was
      caused by C. neoformans. The patient's ratio of peripheral blood CD4(+) cell was
      slightly reduced. After 14 days of treatment with oral fluconazole, followed by
      oral itraconazole for 2 months, mycological and clinical cure were achieved. The
      two isolates were identified as C. neoformans var. gattii serotype C and C.
      neoformans var. grubii serotype A.

PMID- 15982205
TI  - Identification of Malassezia species from Tunisian patients with pityriasis
      versicolor and normal subjects.
AB  - BACKGROUND: The genus Malassezia (Pityrosporum), recognized as a member of
      microbiological flora of the skin in humans and warm-blooded animals, has been
      recently revised to include 10 Malassezia species. The aim of the study was the
      isolation, identification and analysis of Malassezia species distribution in skin
      of healthy volunteers and lesions of pityriasis versicolor (PV). MATERIAL AND
      METHODS: Specimens were taken from 100 patients with PV and 30 healthy
      volunteers. Cultures were made in modified Dixon agar medium and the isolates
      were identified by morphological and physiological methods: macroscopy,
      microscopy, catalase, beta-glucosidase and lipid assimilation tests. RESULTS:
      Malassezia globosa was the predominant species in lesional skin of PV (65%). It
      was isolated alone in 47% of cases and associated in 18% with M. furfur (13%) or
      M. sympodialis (5%). In healthy skin M. globosa was found alone in 7.77% and
      associated in 15.54%, respectively, with M. furfur (4.44%), M. sympodialis
      (4.44%), M. restricta (3.33%) and M. slooffiae (1.11%). CONCLUSION: From these
      findings it was suggested that M. globosa presents the main species implicated in
      the pathogenicity of PV and M. furfur as the second agent of importance.

PMID- 15982206
TI  - In vitro susceptibility of 15 strains of zygomycetes to nine antifungal agents as
      determined by the NCCLS M38-A microdilution method.
AB  - The in vitro susceptibility of 15 strains of six genera of zygomycetes including
      Rhizopus oryzae (Rhizopus arrhizus), Rhizopus stolonifer, Mucor circinelloides
      (three), Absidia corymbifera (three), Rhizomucor pusillus (three), Cunninghamella
      bertholletiae (two), and Syncephalastrum racemosum (two) to nine antifungal
      agents were determined by the NCCLS M38-A broth microdilution method. Geometric
      means of the minimal inhibitory concentrations (MIC) were: amphotericin B 0.07 mg
      l(-1) (range 0.03-0.5 mg l(-1)), nystatin 0.83 mg l(-1) (range 0.25-4 mg l(-1)),
      itraconazole 0.59 mg l(-1) (range 0.03 to >8 mg l(-1)), voriconazole 6.50 mg l(
      1) (range 2 to >8 mg l(-1)), ciclopiroxolamine 1.59 mg l(-1) (range 0.5-4 mg l(
      1)), and amorolfine 9.19 mg l(-1) (range 1 to >16 mg l(-1)). All strains were
      resistant to 5-flucytosine, fluconazole (MIC >64 mg l(-1)) and caspofungin (MIC
      >16 mg l(-1)).

PMID- 15982207
TI  - Candidaemia in an Irish tertiary referral hospital: epidemiology and prognostic
      factors.
AB  - There were two parts to this study. Part 1 evaluated the epidemiology of Candida
      bloodstream isolates within the Southern Health Board (SHB) of Ireland from 1992
      to 2003 by retrospective surveillance of all such isolates of patients reported
      from SHB hospitals to our laboratory database during that period. Part 2 reviewed
      candidaemia cases occurring in Cork University Hospital (CUH) from 1999 to 2003
      using surveillance of all positive blood culture isolates in CUH microbiology
      laboratory during the 5-year period. In part 1, 250 Candida bloodstream isolates
      were reported in the SHB over 12 years. There was a pattern of decreasing
      percentage of C. albicans with time. Whereas in part 2, 63 cases of candidaemia
      were identified in CUH from 1999 to 2003. Candida albicans constituted 50% of all
      isolates, while C. parapsilosis and C. glabrata accounted for 21.2% and 18.2%
      respectively. Average annual incidence rate was 0.48 episodes/1000 admissions and
      0.70 episodes/10 000 patient-days. Vascular catheters were the commonest source
      of candidaemia (61.9%) followed by the urinary tract (12.7%). Risk factors
      included exposure to multiple antibiotics (75%); central vascular catheterization
      (73%); multiple colonization sites (71%); severe gastrointestinal (GI)
      dysfunction (54%) and acute renal failure (43%). Crude 7-day and 30-day mortality
      rates were 20.6% and 39.7% respectively. Logistic regression multivariate
      analysis identified the following to be independent predictors for mortality: age
      > or =65 years [odds ratio (OR) 7.2, P = 0.013]; severe GI dysfunction (OR 10.6,
      P = 0.01); acute renal failure (OR 7.6, P = 0.022); recent/concurrent bacteraemia
      (OR 5.2, P = 0.042); endotracheal intubation (OR 7.7, P = 0.014); while major
      surgery was associated with a better prognosis (OR 0.05, P = 0.002). Appropriate
      antifungal treatment was also found to be associated with survival (Fisher's
      exact test, P < 0.001). The epidemiology of Candida bloodstream isolates within
      our health board had changed over the years. Incidence and mortality of
      candidaemia were relatively high in our hospital. Dysfunction of major organ
      systems and recent bacteraemia were found to predict mortality.

PMID- 15982208
TI  - Dermatophytoses in forestry workers and farmers.
AB  - To assess the frequency of superficial mycoses in forestry workers and farmers in
      the rural region of Duzce, a total of 467 residents of the rural region were
      examined for dermatomycosis infection. Of these, 349 were forestry workers and
      118 farmers. All specimens collected were analysed by direct microscopy and
      culture. Tinea pedis et manus was found in 23 (19.4%), and onycomycosis in 21
      (17.7%) farmers. Tinea pedis et manus was found in 50 (14.3%), and onycomycosis
      in 28 (8%) forestry workers. One tinea corporis, two tinea inguinalis and two
      erosio interdigitalis cases were determined in the farmer group but no cases of
      tinea corporis, tinea inguinalis, or erosio interdigitalis were found in the
      forestry group. In total, five tinea versicolor cases were found in the two
      groups on clinical examination but no agent positivity was yielded in mycological
      cultures. The most frequently isolated agent in the two groups was Trichophyton
      rubrum. The frequencies of superficial mycosis and onychomycosis were found to be
      higher in the farmer group than in the forestry group, although similar
      aetiological agents were isolated in both groups. The farmers had greater rates
      of contact with pathogenic fungi present in soil as well as from infected farm
      animals than the foresters; furthermore, animal husbandry, and the wearing of
      rubber shoes and nylon socks were more frequent in the farmer group. These
      results suggest that habits such as the wearing of rubber shoes and nylon socks,
      and the practice of animal husbandry may be the most important factors in
      determining the frequency of superficial mycoses and aetiological agents in
      forestry workers and farmers. To our knowledge, there is no previous report about
      dermatophytoses in forestry workers.

PMID- 15982209
TI  - An outbreak of Pichia ohmeri infection in the paediatric intensive care unit:
      case reports and review of the literature.
AB  - Since the first report in 1998, 10 cases of Pichia ohmeri infection have been
      reported in the literature. Here we present two new cases of P. ohmeri infection
      in the paediatric age group. The first case was an 8-month-old male infant, who
      was admitted with fever, convulsions and altered consciousness. Conservative
      therapy was started with a presumptive diagnosis of encephalitis. The patient
      failed to respond to the given treatments and died on the 21st day of
      hospitalisation. The second case was a 10-year-old male with B-cell acute
      lymphoblastic leukaemia. He was hospitalised with neutropenic fever. He was
      discharged after 3 weeks of therapy. In both cases P. ohmeri was identified in
      blood samples. Growing evidence indicates that P. ohmeri should be added to the
      lengthening list of opportunistic fungal pathogens that can cause infection in
      all ages, including infants, and particularly in those who are immunocompromised.

PMID- 15982210
TI  - Disseminated cryptococcosis in a human immunodeficiency virus-negative patient: a
      case report.
AB  - Cryptococcus neoformans is a widely distributed saprophytic fungus that may cause
      opportunistic infections in normal and immunocompromised individuals particularly
      in patients with HIV infection. Disseminated infection in HIV-negative
      individuals is occasionally seen: a 57-year-old HIV-negative Turkish female
      initially presented with enlarged mediastinal lymph nodes and a large pulmonary
      parenchymal nodule, eventually diagnosed with disseminated cryptococcosis and
      tuberculosis.

PMID- 15982211
TI  - Stromal cells in hemangioblastoma: neuroectodermal differentiation and
      morphological similarities to ependymoma.
AB  - The histogenesis of stromal cells in hemangioblastoma is inconclusive despite a
      long-term controversy. An immunohistochemical and ultrastructural study was
      conducted for 17 cases of cerebellar hemangioblastoma. A wide range of
      immunohistological markers, targeting epithelial, mesenchymal, endothelial and
      neuroectodermal tissues, was used. In all cases, the microscopic hallmark
      characterizing hemangioblastomas, that is, lipid-containing stromal cells and a
      fine capillary network, known as a reticular variant, was noted. Stromal cells
      showed a variable immunoreactivity for neuroectodermal markers, such as S-100
      protein, CD56, CD57, CD99, and neuron-specific enolase. This result, in
      conjunction with the absence of immunoreactivity for epithelial, mesenchymal, and
      endothelial markers, likely suggests neuroectodermal differentiation of stromal
      cells. In three cases, another component, known as a cellular variant, where
      epithelioid tumor cells were arranged in nests encircled by capillaries and/or in
      pseudorosette-like structures, was noted. Glial fibrillary acidic protein
      immunoreactivity, which was totally absent in cases only showing the reticular
      pattern, was noted in two of them, suggesting a distinctive sign of glial
      differentiation in a proportion of hemangioblastomas. Ultrastructurally,
      microvilli-like projections in intracytoplasmic vacuoles were demonstrated in
      stromal cells. This result, taken together with the neuroectodermal hypothesis of
      stromal cells, suggests that hemangioblastomas may occasionally exhibit
      morphological similarities to ependymomas.

PMID- 15982212
TI  - Unique expression of MUC3, MUC5AC and cytokeratins in salivary gland carcinomas.
AB  - The differential diagnosis of salivary gland carcinoma is often difficult because
      of the confusing histopathological features of the different types of salivary
      gland carcinomas. The expression of MUC3, MUC5AC, MUC6, cytokeratin (CK)7 and
      CK20 was studied in 20 mucoepidermoid carcinomas (MEC), 20 adenoid cystic
      carcinomas (AdCC), and 11 acinic cell carcinomas (ACC). All the cases (51/51,
      100%) were positive for CK7, but they were not positive for CK20. All the cases
      (100%) of the MEC were positive for MUC5AC, while all MEC (100%) were negative
      for MUC3. Only two cases (10%) were positive for MUC6. All cases (100%) of AdCC
      were negative for MUC3, MUC5AC and MUC6. Eight cases (73%) of ACC were positive
      for MUC3, but all the cases (100%) were negative for MUC5AC and MUC6. It is
      concluded that the positive expression of MUC5AC is very unique to MEC, and that
      the positive expression of MUC3 is very unique to ACC. These findings will be
      very useful for the differential diagnosis of the salivary gland carcinomas.

PMID- 15982213
TI  - Pyogenic granuloma of the oral cavity: comparative study of its
      clinicopathological and immunohistochemical features.
AB  - There are two histological types of pyogenic granuloma (PG) of the oral cavity:
      the lobular capillary hemangioma (LCH) and non-LCH type. The aim of the present
      study was to examine and compare the clinical features, etiological factors,
      diameter of vascular elements and immunohistochemical features of LCH and non-LCH
      histological types of PG to determine whether they are two distinct entities.
      Thirty cases of LCH and 26 cases of non-LCH PG were retrieved and retrospectively
      studied. Clinically, LCH PG occurred more frequently (66.4%) as sessile lesion
      whereas non-LCH PG occurred as pedunculated (77%). Non-LCH PG was associated more
      frequently (86.4%) with etiological factors. The lobular area of the LCH PG
      contained a greater number of blood vessels with small luminal diameter than did
      the central area of non-LCH PG. In the central area of non-LCH PG a significantly
      greater number of vessels with perivascular mesenchymal cells non-reactive for
      alpha-smooth muscle actin and muscle-specific actin was present than in the
      lobular area of LCH PG. The differences found in the present study suggest that
      the two histological types of PG represent distinct entities.

PMID- 15982214
TI  - Helicobacter heilmannii infection: clinical, endoscopic and histopathological
      features in Japanese patients.
AB  - Gastric biopsy materials of 4074 consecutive Japanese patients undergoing
      esophagogastroduodenoscopy were reviewed, along with those of 15 patients with
      Helicobacter heilmannii infection (11, chronic gastritis; four, mucosa-associated
      lymphoid tissue (MALT) lymphoma). In four patients with H. heilmannii infection,
      the materials were examined by transmission electronmicroscopy. Urea breath test
      (three patients) and antibody test (five patients) were performed in patients
      with H. heilmannii infection. In two patients with MALT lymphoma, H. heilmannii
      was eradicated. The prevalence of H. heilmannii was 0.1% in the consecutive
      series. In chronic gastritis, the gastric mucosa was endoscopically normal
      (13.3%), had erythema (33.3%), or had erosions (53.3%); histologically, it showed
      no epithelial change, mild mononuclear cell infiltration, and slight and focal
      neutrophil infiltration; Helicobacter heilmannii was positive with anti-H. pylori
      antibody, and was detected in the mucous gel layer and in foveolae. In MALT
      lymphoma, the gastric mucosa was coarsely granular with enlarged mucosal folds
      without ulcers (two cases), with small ulcers (one case), or with multiple
      erosions (one case). Urea breath test and antibody test were both negative.
      Eradication of H. heilmannii resulted in remission of MALT lymphoma. Helicobacter
      heilmannii infection is therefore uncommon in Japanese adults, but is associated
      with chronic gastritis and gastric MALT lymphoma.

PMID- 15982215
TI  - Distinct clinicopathological entity 'autoimmune pancreatitis-associated
      sclerosing cholangitis'.
AB  - Autoimmune pancreatitis (AIP) is a recently proposed disease entity, in which an
      elevated serum IgG4 is characteristic. This disease is sometimes associated with
      other inflammatory diseases: Sjogren's disease, or sclerosing cholangitis. The
      aim of the present paper was to examine the difference in pathophysiology between
      AIP-associated sclerosing cholangitis (AIP-SC) and primary sclerosing cholangitis
      (PSC). The clinicopathological findings and the immunohistochemical expressions
      of IgG subclasses (IgG1, IgG2, IgG3, and IgG4) were evaluated for the two
      aforementioned diseases (six patients with each disease). Radiologically, the
      extrahepatic bile duct was involved in AIP-SC, whereas both extrahepatic and
      intrahepatic bile ducts were involved in PSC. Clinically, bile duct lesions in
      the former responded well to steroid therapy. Histologically, various degrees of
      mononuclear cell infiltration and fibrosis around bile ducts and portal tracts
      were found in all patients. Immunohistochemically, the IgG4-positive plasma
      cell/mononuclear cell ratio was significantly higher in AIP-SC than in PSC (P <
      0.05). The IgG4-positive plasma cell/mononuclear cell ratio is a useful index to
      help distinguish AIP-SC from PSC. A mechanism similar to that involved in AIP may
      be involved in AIP-SC. The latter is a distinct clinicopathological entity that
      should be distinguished from PSC because it responds well to steroid therapy.

PMID- 15982216
TI  - Reproducible and clinically meaningful differential diagnosis is possible between
      lobular endocervical glandular hyperplasia and 'adenoma malignum' based on common
      histopathological criteria.
AB  - The aim of the present study was to determine if the differential diagnosis
      between lobular endocervical glandular hyperplasia (LEGH) and minimal deviation
      adenocarcinoma (MDA), or 'adenoma malignum', is reproducible when clear criteria
      for these two lesions are given. A total of 44 proliferative endocervical
      glandular lesions were collected, for which differential diagnosis from MDA was
      considered to be necessary. Seven observers independently classified these 44
      lesions into LEGH, LEGH with adenocarcinoma in situ (AIS), MDA, or common
      cervical adenocarcinoma, according to the following criteria: LEGH was non
      invasive proliferation of endocervical glandular cells without any obvious
      adenocarcinoma component. MDA was very well-differentiated endocervical-type
      mucinous adenocarcinoma composed mostly of LEGH-looking glands but containing the
      component of obviously invasive adenocarcinoma. LEGH with AIS was defined as
      continuous coexistence of LEGH and AIS. Among these four diagnostic categories,
      the interobserver agreement level was substantial (kappa = 0.618). The level
      increased to almost perfect (kappa = 0.928) between the group of non-invasive
      lesions consisting of LEGH and LEGH with AIS and the other group of invasive
      lesions comprising MDA and common adenocarcinoma. When the modal diagnosis was
      adopted as the final diagnosis for individual lesions, the 5 year survival rate
      of patients after surgery was 100% for the non-invasive lesions but only 54% for
      the invasive lesions (P < 0.01). It is clearly shown that reproducible
      differential diagnosis is possible between LEGH, LEGH with AIS, and MDA and that
      such a differentiation is clinically meaningful.

PMID- 15982217
TI  - Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary
      pattern.
AB  - Micropapillary differentiation in adenocarcinomas has recently been associated
      with poor prognosis because these tumors are more likely to metastasize. However,
      no clear explanation exists as to why the presence of a micropapillary pattern is
      associated with metastasis. A case of primary lung adenocarcinoma with a
      prominent micropapillary pattern is presented here, with special reference to the
      immunohistochemical expression of the E-cadherin-mediated system and IQGAP1.
      Histologically, the tumor was diagnosed as a moderately differentiated papillary
      adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary
      metastases, pulmonary disseminations, lymphovascular invasions, and lymph node
      metastases. Immunohistochemically, positive staining for the adhesion molecules E
      cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary
      and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary,
      but not in the non-micropapillary, area. The adhesive function of E-cadherin
      depends on the integrity of the entire cadherin-catenin-actin network, and thus
      the expression of IQGAP1 may lead to adherens junction disassembly, and
      consequently, the release of carcinoma cells organizing in a micropapillary
      pattern. This is the first report to suggest correlation between adenocarcinoma
      with a micropapillary pattern and the presence of adhesion molecules, and offers
      an intriguing first glimpse on the role of the micropapillary pattern in the
      process of metastasis.

PMID- 15982218
TI  - Malignant T-cell lymphoma of the thyroid gland associated with Hashimoto's
      thyroiditis.
AB  - Reported herein is a rare case of malignant T-cell lymphoma of the thyroid gland
      that developed in a 71-year-old woman with a past history of chronic thyroiditis.
      The chief complaints were rapidly growing neck mass, weight loss and hoarseness.
      Presence of abnormal lymphoid cells in the peripheral blood, and an increase in
      anti-microsome antibodies and anti-thyroglobulin antibodies were found on
      preoperative laboratory tests. A diagnosis of suspicious malignant lymphoma of
      the thyroid gland accompanied by Hashimoto's thyroiditis was made, and a total
      thyroidectomy was performed. Histological examination revealed diffuse small
      lymphocytic infiltration in the thyroid gland associated with Hashimoto's
      thyroiditis. Immunohistochemical examination showed that the small lymphocytes
      were positive for T-cell markers with CD4 predominance. Southern blot analysis of
      tumor specimens revealed a monoclonal T-cell receptor gene rearrangement.
      Peripheral T-cell lymphoma was diagnosed. No adjuvant therapy was performed
      because of the tumor stage and its subtype. The patient is well with no
      recurrence or metastasis 25 months after the surgical removal of the thyroid. The
      present case suggests that Hashimoto's thyroiditis might play an important role
      in the carcinogenesis of thyroid lymphoma not only of B-cell lineage but also of
      T-cell lineage.

PMID- 15982219
TI  - Cutaneous reactive angiomatosis occurring in erythema ab igne can cause atypia in
      endothelial cells: potential mimic of malignant vascular neoplasm.
AB  - Erythema ab igne (EAI), an old and rare disease, is an erythematous, often
      pigmented, reticular, macular dermatosis that occurs at the site of repeated
      exposure to moderate heat. Reported herein is an unusual case of EAI occurring in
      a 33-year-old woman with a very broad lesion of reticular erythema and
      pigmentation on the lower extremities. The patient frequently put her lower
      extremities close to a heater in the wintertime to alleviate chill. The lesion
      started a decade ago, and it gradually became conspicuous. Microscopic findings
      showed a proliferation of small blood vessels in a thickened papillary dermis,
      not as typical as seen in EAI, but as seen in cutaneous reactive angiomatosis.
      They were arranged as small lobules and associated with hyalinization, edema and
      delicate fibroplasia. Many vessels were lined by plump endothelial cells, some of
      which had enlarged hyperchromatic nuclei. Many of these cells were
      multinucleated. Similar-appearing cells were associated with concentric foci of
      hyalinization without vascular lumina. A few atypical mitoses were observed. The
      lesion became much less conspicuous after the patient started avoiding close
      exposure to a heater, without any other special treatments. The aforementioned
      changes may be confused with malignant vascular neoplasm because of unusual
      cytological atypia and atypical mitoses in the endothelial cells.

PMID- 15982220
TI  - Serous cystadenocarcinoma of the pancreas.
AB  - A case of serous cystadenocarcinoma of the pancreas in an 85-year-old woman is
      reported. The tumor extensively involved the body and tail of the pancreas and
      contiguously invaded the spleen. The histopathology of the tumor was similar to
      that of serous cystadenoma, but mild nuclear hyperchromatism and atypism were
      noted, and the neoplastic invasion of nerve fibers in the stroma was observed. In
      the spleen neoplastic cells forming microcysts were diffusely insinuated in the
      red pulp without the fibrous stroma. The patient is in good health without
      recurrence and metastasis after the operation. The present case is the second
      example of this kind of neoplasm that showed direct splenic invasion. Because
      serous cystadenocarcinoma of the pancreas exhibits bland cytological features,
      diligent search for the invasion of the surrounding tissue or peripheral nerves
      is needed for the differentiation from its benign counterpart.

PMID- 15982221
TI  - Xanthogranulomatous inflammation presenting as a submucosal mass of the sigmoid
      colon.
AB  - Xanthogranulomatous inflammation (XGI) is a well-recognized disease process in
      the kidney and gallbladder. However, involvement of the colon is extremely rare.
      On the other hand, it is important to recognize that clinically and
      radiologically, XGI could be misinterpreted as an infiltrative cancer. Recently
      the authors encountered a 38-year-old woman who presented with a submucosal mass
      like lesion in the sigmoid colon. Radiological imaging had also suggested a
      possibility of sigmoid colon cancer as well as pelvic inflammatory disease or
      actinomycosis. Although XGI may rarely occur in the large bowel, it should be
      considered in patients with a colonic submucosal mass. In addition, it is
      important to make an intraoperative pathological diagnosis in order to avoid any
      excessive operative stress.

PMID- 15982222
TI  - Adenoid basal carcinoma of the uterine cervix: report of two cases with reference
      to adenosquamous carcinoma.
AB  - Adenoid basal carcinoma (ABC) of the uterine cervix is a rare neoplasm with
      excellent prognosis. Differential diagnosis between ABC and an ABC-like lesion of
      adenosquamous cell carcinoma (ASC) of the cervix is important due to their
      contrasting prognosis. Reported herein are two cases of ABC that have been
      compared with seven ASC exhibiting ABC-like lesions from approximately 2600
      resected uterine cervical malignancies diagnosed at Shikoku Cancer Center. The
      two ABC were incidentally found in the uterine cervix of 69-year-old and 59-year
      old Japanese women due to cervical intraepithelial neoplasia grade 3 and to
      squamous cell carcinoma, respectively. The ABC consisted of infiltrating nests of
      basaloid cells with low nuclear atypia. The patients remained alive without
      recurrence for 9 years and 18 months, respectively. An ABC-like lesion was
      defined as basaloid cell nests simulating ABC, but with some features indicating
      malignant potential. However, the differential diagnosis was sometimes difficult
      because two of seven ABC-like lesions were originally diagnosed as ABC.
      Immunohistochemically, cytokeratin 7 was negative for the basaloid cells of two
      ABC, but positive for six of six ABC-like lesions of ASC, while cytokeratin 8 was
      positive for both ABC and ASC. This cytokeratin pattern might provide a good tool
      for distinguishing between ABC and an ABC-like lesion of ASC when the
      histological findings are equivocal.

PMID- 15982223
TI  - Lymphocyte transformation test in patients with allergic contact dermatitis.

PMID- 15982224
TI  - Cross-reactivity between nickel and palladium demonstrated by systemic
      administration of nickel.
AB  - Concomitant patch test reactions to nickel and palladium have frequently been
      reported in patients undergoing investigation because of suspected allergic
      contact dermatitis. Theoretically, these reactions can be explained by multiple,
      concomitant, simultaneous sensitization as well as cross-sensitization. We
      studied whether concomitant reactions to nickel and palladium could represent
      cross-sensitization in females hypersensitive to combinations of nickel,
      palladium and cobalt. Females were patch tested with serial dilutions of nickel
      sulfate, cobalt chloride and palladium chloride on the upper back. 1 month later,
      when the patch test reactions were gone, the patients were randomized into 2
      groups that were challenged orally with either nickel or placebo. 1 day later,
      the areas of previous positive patch test reactions were read in a blind way
      looking for flare-up reactions. Nickel provocation but not placebo yielded flare
      up reactions on sites previously tested with nickel (P = 0.012) and palladium (P
      = 0.006), but were also observed on sites previously tested with cobalt, even
      though this was not statistically significant. Flare-up reactions of previous
      patch test reactions to nickel and palladium after oral challenge with nickel
      speak in favour of a cross-reactivity mechanism.

PMID- 15982225
TI  - Unintended cutaneous reactions to CS spray.
AB  - CS spray (2-chlorobenzylidene malononitrile 5% w/v in methyl isobutyl ketone) has
      been used by the police force in the UK as an incapacitant for nearly a decade.
      It causes a number of well-recognized cutaneous reactions, which are generally
      regarded as short-lived. These include skin burning, erythema and blistering.
      However, a range of unpredictable cutaneous reactions to CS spray may also occur.
      We have found contact allergy, leukoderma, initiation or exacerbation of
      seborrhoeic dermatitis, and aggravation of rosacea following CS spray exposure in
      6 police officers and 1 doorman. These skin reactions have required long-term
      changes in working practice for the affected individuals. Police officers may
      have repeated exposure to CS spray during their training and in their work, and
      designated police officers carry CS spray canisters daily in the line of duty.
      They may therefore be at greater risk of exposure to CS spray and its unintended
      effects than many assailants.

PMID- 15982226
TI  - Chemical exposure and symptoms of hand dermatitis in construction painters.
AB  - Studies on the prevalence of hand dermatitis in construction painting are rare.
      Our aim was to study the painters' chemical exposure and the prevalence of self
      reported skin symptoms on hands and forearms. A cross-sectional questionnaire
      survey was conducted on 1000 Finnish male construction painters and 1000
      carpenters (response rates 60.6% and 60.4%, respectively). We used 2 definitions
      for symptom-based hand dermatitis (liberal > or = 2 symptoms and strict criteria
      > or = 3) and logistic regression analysis, adjusted with age and atopy. Painters
      reported more symptoms of hand dermatitis than carpenters (12-month prevalence
      22.5% and 14.2%, P < 0.05; strict criteria 13.3% and 6.4%, P < 0.05). A dose
      response relationship was found for reporting symptoms and exposure to several
      solvent-based (SB) and water-based (WB) products. When exposure was combined into
      1 variable, daily use of SB epoxy/urethane paints (OR 5.3, 95% CI 2.2-12.9;
      strict criteria 6.8, 2.3-19.9) and WB putties/plasters (1.9, 1.2-3.0; strict
      criteria 2.0, 1.1-3.9) were associated with hand dermatitis, whereas using only
      WB paints was not a risk factor. In conclusion, painters reported significantly
      more symptoms of hand dermatitis than carpenters. Putties/plasters emerged as a
      risk factor for dermatitis in construction painting.

PMID- 15982227
TI  - Extraction of haptens from solid products and their delivery to the skin,
      exemplified by dithiocarbamates from rubber gloves.
AB  - Allergic contact dermatitis is often caused by solid products such as rubber
      gloves. Patch testing with the product as is often gives negative results.
      Extraction of the haptens into an organic solvent is commonly performed to
      achieve a more correct investigation. The technique used for extraction of
      haptens from solid materials is only sporadically described. In this study, we
      investigated and optimized the yields of dithiocarbamates obtained by extraction
      from rubber gloves. The influence of solvent, extraction time and the procedures
      for extraction are evaluated. The delivery of zinc dibutyldithiocarbamate from
      the patch test preparation to the skin is determined.

PMID- 15982228
TI  - Preservatives in registered chemical products.
AB  - Preservatives are common causes of contact allergy and contact dermatitis.
      Exposure to cosmetics, personal care products, consumer products and
      occupationally used products often involve contact with the same range of
      preservatives. The aim of this study is to provide an overview on the occurrence
      of preservatives in registered chemical products. The studied preservatives
      included substances from standard patch test series and other preservatives
      relevant for registered chemical products. Data obtained from the Danish Product
      Register Database (PROBAS) in January 2005 were compared to similar data from
      January 2002. Paints/lacquers, cleaning agents and printing inks were the most
      frequently registered product categories, and the studied preservatives were
      registered in most of the product categories included in the study. For most
      product categories the total number of registered products was stable during the
      study period. Butylated hydroxytoluene, benzoic acid, isothiazolinones, Bronopol
      and formaldehyde showed an increase from 2002 to 2005. Most of these changes
      occurred in the product category paints/lacquers, for which a doubling mainly due
      to a change in registration practice was observed. The frequent registration of
      isothiazolinones (MCI/MI and benzisothiazolinone) in paints/lacquers may be a
      possible explanation for the relative high and stable frequency of positive patch
      test reactions to MCI/MI.

PMID- 15982229
TI  - A temporary henna tattoo causing hair and clothing dye allergy.
AB  - Contact dermatitis following the application of temporary paint-on henna tattoos
      indicates a potentially serious problem of active sensitization. We describe 2
      cases involving sisters who travelled to Bali together and acquired a temporary
      black henna tattoo to the lower back region. Both sisters subsequently developed
      a contact dermatitis at the tattoo site, the dermatitis disseminating in one
      sister. There was persistent hyperpigmentation at the tattoo site in both sisters
      several months after the application. Patch testing revealed a positive reaction
      to para-phenylenediamine (PPD) in both sisters. One sister also showed reactions
      to other hair dyes and to multiple organic dyes. Allergic contact dermatitis to
      PPD contained in temporary henna tattoos is an increasing problem worldwide, with
      cross-reaction to related compounds and permanent skin changes, a frequent
      consequence of sensitization to this significant allergen.

PMID- 15982230
TI  - 10 years' experience of patch testing with a shoe series in 230 patients: which
      allergens are important?
AB  - Over a 10-year period, 230 patients with foot dermatitis were patch tested to a
      shoe series of allergens. About 54 (23%) had relevant allergic positive reactions
      to one or more allergens. The commonest relevant allergens groups were, in order,
      chromate, medicaments, rubber chemicals, dyes and cosmetic constituents, with the
      most frequent individual allergens being chromate (4%), neomycin (3%), rubber
      chemicals (> 3%), paraphenylenediamine (2%) and tixocortyl pivolate (2%). Some
      allergens previously thought to be important, e.g. certain plastic and adhesive
      chemicals, did not show any positives over the period of study. In addition, para
      tertiary butyl phenol formaldehyde resin was a relatively unimportant allergen in
      this series. The main practical points to emerge from this study are that, in
      patients with foot dermatitis, chromate is still the principal allergen, and that
      medicament and cosmetic allergens may be prominent.

PMID- 15982231
TI  - Patch test reactions to cosmetic allergens in 1995-1997 and 2000-2002 in Finland-
      a multicentre study.
AB  - Contact sensitivity to cosmetics is common, but the sensitizing chemicals vary
      between countries and study periods. The present survey aimed at revealing the
      recent trends in patch test sensitivity with cosmetic chemicals in Finland. We
      report a retrospective multicentre survey of patch test reactions focusing on
      cosmetic-related substances and comparing the test results in 1995-97 with those
      in 2000-02. The most striking increases in the frequency of the patch test
      sensitivity were found with balsam of Peru and propolis from 4.0% to 6.2% (P <
      0.001) and from 0.5% to 1.4% (P < 0.001), respectively, whereas the most
      prominent decreases were found with methylchloro/methylisothiazolinone and
      chlorhexidine diglugonate from 2.4% to 1.3% (P < 0.001) and from 1.2% to 0.5% (P
      < 0.001), respectively. The level of patch test sensitivity to methyldibromo
      glutaronitrile increased, although not significantly, from 1.0% to 1.5%. An
      increasing tendency was also found with hair dye chemicals 4-aminophenol and
      toluene-2,5-diamine or toluene-2,5-diamine sulfate from 1.3% to 3.8% and from
      1.4% to 5.2%, respectively, while such a tendency was not found among permanent
      wave chemicals. The sensitivity level of fragrance mix remained the same (6% -
      7%). We conclude that surveys revealing the state of sensitivity to cosmetic
      chemicals should be performed periodically in different countries.

PMID- 15982232
TI  - Allergic contact dermatitis from natural rubber latex in atopic dermatitis and
      the risk of later Type I allergy.
AB  - The aims of the study were to assess whether contact dermatitis in children could
      be due to a delayed hypersensitivity reaction to natural rubber latex (NRL) and
      to define risk factors for later occurrence of Type I hypersensitivity to this
      allergen. Among 1800 children investigated for contact dermatitis, 55 were
      referred on suspicion of rubber allergy and had patch tests to NRL, as well as
      prick tests and blood tests for specific immunoglobulin E (IgE). A 2-year follow
      up was then carried out. Delayed hypersensitivity to NRL was confirmed in 32
      children. Patch testing with NRL proved to be positive, and clinical improvement
      confirmed the diagnosis and relevance of patch tests. 30 of these 32 patients had
      associated atopic dermatitis (AD). Prick tests and blood tests for specific IgE
      to latex were negative at the time of diagnosis. A 2-year follow-up showed that
      10 of 27 patients presenting initially with a positive patch test without
      associated Type I sensitization later developed immediate hypersensitivity.
      Children with AD are at high risk for allergy to NRL protein. Exclusion of this
      allergen should be strongly advised in atopics because of the dual risk of
      dermatitis and later evolution into severe Type I hypersensitivity.

PMID- 15982233
TI  - Contact sensitivity to cigarettes.

PMID- 15982235
TI  - Erythema multiforme induced by acetaminophen: a recurrence at distant sites
      following patch testing.

PMID- 15982234
TI  - Positive lymphocyte transformation test in a patient with allergic contact
      dermatitis of the scalp after short-term use of topical minoxidil solution.
AB  - Topical 2,4-diamino-6-piperidinopyrimidine-3-oxide (minoxidil) solution has been
      widely used for the treatment of androgenetic alopecia for over 15 years now and
      the substance is currently approved for this indication in 2% and 5% formulation.
      Typical side effects of this topical treatment include irritative dermatitis
      going along with pruritus, erythema, scaling and dryness, which occur especially
      at the onset of the therapy. In some cases, allergic contact dermatitis or
      exacerbation of seborrheic dermatitis has been reported. While most of the
      patients with allergic contact dermatitis described in the literature showed a
      positive sensitization to the vehicle substance propylene glycol evaluated by
      patch testing, reactions to the active ingredient minoxidil are rare. Here, we
      report a case of allergic sensitization to minoxidil, which we evaluated and
      differentiated from an irritative reaction by a combination of patch testing and
      lymphocyte transformation test. The differentiation of allergic and irritative
      adverse effects and the identification of the causative allergen are of major
      relevance for the proceeding and adjustment of the therapy. Patients with
      sensitizations against propylene glycol are candidates for preparations with
      alternative solvents but can proceed treatment with minoxidil. In contrast,
      patients with allergies to the active ingredient itself are no longer candidates
      for treatment with minoxidil and should undergo alternative therapeutic options.

PMID- 15982236
TI  - Delayed-type hypersensitivity to protamine as a complication of insulin therapy.

PMID- 15982237
TI  - Phototoxic dermatitis due to Chenopodium album in a mother and son.
AB  - Chenopodium album L. subs. album (Chenopodiaceae) is an annual herb with fibrous
      roots. The plant grows worldwide and frequently in moist areas. Sometimes, the
      young parts of this plant can be cooked and eaten as a vegetable. In this
      article, we report a mother and her adult son, in whom phototoxic reaction
      developed on the sun-exposed body areas after eating this plant of Chenopodiaceae
      family because of rare presentation. We thought that this reaction was probably
      due to furocoumarins constituent within the plant.

PMID- 15982238
TI  - Allergic contact dermatitis caused by 6alpha-methylprednisolone aceponate.

PMID- 15982240
TI  - A series of four cases of allergic contact dermatitis to phthalic
      anhydride/trimellitic anhydride/glycols copolymer in nail varnish.

PMID- 15982241
TI  - Reply to the comments by Coenraads and Tang 'Chloracne due to o-dichlorobenzene
      in a laboratory worker', Contact Dermatitis 2005: 52: 108.

PMID- 15982242
TI  - Measuring quality in clinical education.

PMID- 15982243
TI  - Creating a professional poster presentation: focus on nurse practitioners.

PMID- 15982244
TI  - Atopic dermatitis--more than a simple skin disorder.
AB  - PURPOSE: To describe atopic dermatitis (AD) in relation to a case study, the
      diagnostic criteria, complications, prevalence, future implications, and
      management for the primary care provider. DATA SOURCES: Extensive literature
      review on the condition, supplemented with an actual case study. CONCLUSIONS:
      Although there are many scientific studies done on AD, the exact pathogenesis and
      cure for this condition are still to be discovered. It is usually chronic and has
      some fatal sequelae in those who have been exposed to viral infections. Asthma,
      allergic rhinitis (AR), and AD are considered the atopic triad. Further studies
      that may help improve medical providers' understanding of AD are going on and
      offer hope to those afflicted by this disorder. IMPLICATIONS FOR PRACTICE:
      Children over 5 years old may have outgrown their symptoms, so it is best to
      diagnose this condition at an early age to provide better management outcomes.
      Because it is part of an atopic triad, the nurse practitioner must think beyond
      the presenting skin condition to consider possible respiratory system conditions.
      AD may herald the onset of asthma and AR.

PMID- 15982245
TI  - The nurse practitioner's role in helping patients achieve lipid goals with statin
      therapy.
AB  - PURPOSE: To discuss the merits of statins in achieving lipid goals and the role
      of nurse practitioners (NPs) in improving adherence to medical regimens with the
      goals of improving patient outcomes, reducing cardiovascular disease (CVD) risk
      within the population at large, and enhancing patients' ability to reach their
      individual goals. DATA SOURCES: Original research articles, journal articles,
      professional association practice guidelines. CONCLUSIONS: Despite extensive
      research clearly documenting the relation between lowering low-density
      lipoprotein cholesterol (LDL-C) and decreasing rates of cardiovascular events and
      deaths, lipid-lowering therapy is not being aggressively managed to achieve
      optimal lipid levels and CVDs remain the leading cause of death among adults in
      the United States. Contributing factors include lack of patient adherence with
      prescribed therapy, absence of dose titration when needed, and suboptimal follow
      up. Two pathways to improving compliance are the following: first, use of a
      starting dose of a more efficacious statin to allow more patients to reach their
      LDL-C goal and, second, more effective primary care programs with NPs as team
      leaders who can assess and diagnose patients, then develop individual treatment
      plans and follow-up with patients to ensure that their lipid goals are met.
      IMPLICATIONS FOR PRACTICE: NPs are well suited to manage patients with
      hypercholesterolemia. The NP can bridge all aspects of care for the patient by
      overseeing assessment and treatment of cardiovascular risk factors, including
      elevated levels of LDL-C, initiating pharmacotherapy when needed, and
      establishing for each patient an individualized program that features education,
      support, and follow-up.

PMID- 15982246
TI  - Chronic care management for the elderly: an opportunity for gerontological nurse
      practitioners.
AB  - PURPOSE: To discuss the role that gerontological nurse practitioners (GNPs) may
      play in providing chronic care management for the elderly. DATA SOURCES: Review
      of recent literature on chronic care management, personal experience of the
      authors in caring for older adults under the chronic care management model, and a
      case study. CONCLUSIONS: GNPs are the most appropriate practitioners to provide
      and coordinate chronic care management to the population that needs it most--the
      elderly. IMPLICATIONS FOR PRACTICE: Demographic shifts in the United States have
      increased the number of people with chronic illnesses; however, the nation's
      healthcare delivery system has not significantly evolved to meet the changing
      needs of its population. As a result, many people, especially older adults,
      suffer needlessly, and healthcare costs continue to rise. Chronic care management
      may alleviate older adults' chronic health problems, reduce expenditures for
      their health care, and promote their satisfaction and quality of life.

PMID- 15982247
TI  - Vertebroplasty and kyphoplasty for treatment of painful osteoporotic compression
      fractures.
AB  - PURPOSE: To review the pathophysiology of osteoporosis and describe
      vertebroplasty and kyphoplasty, which are minimally invasive procedures to treat
      the pain associated with vertebral compression fractures (VCFs). DATA SOURCES:
      Extensive literature review of osteoporosis, vertebroplasty, and kyphoplasty
      supplemented by case study and clinical experience in the minimally invasive
      interventional neuroradiology interventions. CONCLUSIONS: Osteoporosis is a
      progressive debilitating process that destroys the cancellous bone, weakening the
      overall integrity and stability of the bone. The loss of bone mass places the
      individual at increased risk for vertebral body, hip, and wrist fractures. In the
      past, there was no treatment option to repair vertebral body deformity or
      instability after osteoporotic VCFs. Management solely relied on the use of
      nonsteroidal anti-inflammatory drugs, narcotics, muscle relaxants, and/or
      orthotic bracing to provide pain relief. VCFs alter the stability of the
      vertebral body and column, and the lack of stabilization can lead to chronic pain
      syndrome, immobility, pulmonary compromise, progression of spinal deformity,
      increase in the risk for additional VCFs, and increase in the risk for
      comorbidities and mortality related to immobility. IMPLICATIONS FOR PRACTICE:
      Vertebroplasty and kyphoplasty are minimally invasive procedures aimed at pain
      control, stabilization of the vertebral body, and with kyphoplasty, the ability
      to provide some correction of deformity with partial restoration of vertebral
      body height. Providing pain control and stabilization of the vertebral column
      improves mobility, thus decreasing the potential risks associated with
      immobility.

PMID- 15982248
TI  - Chronic blood transfusion therapy practices to treat strokes in children with
      sickle cell disease.
AB  - PURPOSE: To identify variations in practices used by nurses for pediatric
      patients with sickle cell disease (SCD) receiving chronic blood transfusion
      therapy for strokes. DATA SOURCES: Descriptive study of a convenience sample of
      11 nurses who care for children with SCD from nine institutions completed a
      closed-ended questionnaire consisting of 37 items. Responses reflected practice
      experience with a total of 189 transfused patients with SCD. CONCLUSIONS: A wide
      range of nursing practices exists for blood transfusion therapy for children with
      SCD and strokes. Manual partial exchange transfusion (66%) was the most commonly
      used method for blood transfusion in children with strokes reported among the
      nurses surveyed. Simple transfusions and erythrocytapheresis account for 21% and
      13% of the practices reported. Opportunities exist to establish evidence-based
      nursing care guidelines to improve the care of children with strokes receiving
      blood transfusion therapy. IMPLICATIONS FOR PRACTICE: A wide range of local
      standard care guidelines for blood transfusion therapy exists. The results of
      this survey indicate that partial manual exchange transfusion is the most
      commonly used method of chronic blood transfusion therapy in children with SCD
      and stroke despite the fact that the magnitude of benefit in comparison with
      simple transfusion has not been established. Factors such as peripheral venous
      access, compliance with current chelation regimen, and the presence of antibodies
      are important considerations in the choice of method.

PMID- 15982249
TI  - Rural health alert: Helicobacter pylori in well water.
AB  - PURPOSE: This exploratory research project is an epidemiological study to
      determine in a specified population of farmworkers in Southeast Georgia the
      following: (a) the prevalence rate of gastritis, (b) related cofactors
      contributing to gastritis with or without a positive diagnosis of Helicobacter
      pylori (HP), (c) relationship of contaminated drinking water to gastritis, and
      (d) relative risk of acquiring gastritis from HP-contaminated drinking water.
      DATA SOURCES: Data were collected from five common water sources for 147
      farmworkers in rural Southeast Georgia. Farmworkers were given a survey to
      identify cofactors related to HP gastritis. Water samples were taken from four
      common well water sources (experimental group) and one control well, analyzed for
      HP, and associated through nonparametric categorical data analysis to the survey
      items to discover possible relationships. CONCLUSIONS: Analysis of data using
      nonparametric regression showed a weak positive relationship (p= 0.07) between
      symptoms of gastritis and the HP-contaminated water. Risk analysis demonstrated
      that farmworkers who drank water contaminated with HP were 2.6 times more likely
      to have symptoms of gastritis. IMPLICATIONS FOR PRACTICE: This research
      established a positive relationship between well water contaminated with HP and
      signs and symptoms of gastritis. Nurse practitioners (NPs) working with
      populations who drink well water and have the signs and symptoms or positive
      diagnosis of HP should have a high degree of suspicion that the well water may be
      a source of HP infection. In addition to treating the patient for HP gastritis,
      NPs may utilize this research to plan other interventions that decrease the
      incidence of HP-related illnesses such as recommending well water treatment.

PMID- 15982251
TI  - MHC immunoevasins: protecting the pathogen reservoir in infection.
AB  - Alteration of antigen recognition by T cells as result of insufficient major
      histocompatibility complex (MHC)-dependent antigen-presenting function has been
      observed in many cases of infections, particularly in in vitro systems. To hide
      themselves from an efficient immune response, pathogens may act on MHC-related
      functions at three levels: (i) by limiting the number of potential antigens that
      can be presented to naive T cells; (ii) by synthesizing proteins which directly
      affect MHC cell-surface expression; and (iii) by altering the normal
      intracellular pathway of peptide loading on MHC. Here, we review examples of
      pathogens' action on each single step of MHC function and we suggest that the
      result of these often synergistic actions is both a limitation of the priming of
      naive T cells and, more importantly, a protection of the pathogen's reservoir
      from the attack of primed T cells. The above mechanisms may also generate a
      skewing effect on immune effector mechanisms, which helps preserving the
      reservoir of infection from sterilization by the immune system.

PMID- 15982252
TI  - Major histocompatibility complex class I polymorphism in Asiatic lions.
AB  - Asiatic lions (Panthera leo persica), whose only natural habitat in the world is
      the Gir forest sanctuary of Gujarat State in India, are highly endangered and are
      considered to be highly inbred with narrow genetic diversity. An objective
      assessment of genetic diversity in their immune loci will help in assessing their
      survivability and may provide vital clues in designing strategies for their
      scientific management and conservation. We analyzed the comparative sequence
      polymorphism at exon 2 and exon 3 of major histocompatibility complex (MHC) class
      I in three groups of lions, i.e. wild Asiatic (from Gir forest), captive-bred
      Asiatic (from zoological parks in India), and Afro-Asiatic hybrid groups (from
      zoological parks in India) through polymorphism chain reaction-assisted sequence
      based typing. The two exons were amplified, cloned, sequenced, and analyzed for
      polymorphism at nucleotide and putative translated product level. The analysis
      revealed extensive sequence polymorphism not only between clones derived from
      different lions but also the clones derived from a single lion. Furthermore, the
      wild Asiatic lions of Gir forest exhibited abundant sequence polymorphism at MHC
      class I comparable with that of Afro-Asiatic hybrid lions and significantly
      higher than that of captive-bred Asiatic lions. We hypothesize that Asiatic lions
      of Gir forest are not highly inbred as thought earlier and they possess abundant
      sequence polymorphism at MHC class I loci. During this study, 52 new sequences of
      the multigene MHC class I family were also identified among Asiatic lions.

PMID- 15982253
TI  - Chimerism analysis by sex determining region Y (SRY) and major histocompatibility
      complex markers in non-human primates using quantitative real-time polymerase
      chain reaction.
AB  - The ability to discriminate and further quantify the proportion of donor and host
      cells is essential in hematopoietic stem cell transplant protocols. In human sex
      mismatched transplants, this can be easily accomplished by the use of
      commercially available fluorescent in situ hybridization (FISH) probes. In many
      animal models, including non-human primates, this methodology is not possible due
      to the lack of commercially available FISH probes. In animal models, donor cell
      detection could be accomplished if there is a known species-specific sex
      determining region Y (SRY) (male) or other unique DNA sequence using either
      semiquantitative or quantitative real-time polymerase chain reaction (PCR). The
      use of real-time quantitative PCR has the obvious advantage of providing detailed
      enumeration of the percentage of donor cells present. We report the development
      of extremely sensitive primer and probe combinations for male (SRY) and major
      histocompatibility complex (MHC)-DQA sequences in the macaque and baboon non
      human primate models. This assay has a sensitivity of a five-log range and can
      detect less than four target cells in the presence of 10(5) background cells
      (approximately 0.001%) and fetal DNA obtained from maternal serum from Macaca
      nemestrina. The SRY (male) primer and probe combination has similar sensitivity
      in Macaca fasicularis, Macaca mulatta, and Papio cynocephalus anubis.

PMID- 15982254
TI  - HLA genes in Portugal inferred from sequence-based typing: in the crossroad
      between Europe and Africa.
AB  - The human leukocyte antigen-A (HLA-A), -B and -DRB1 polymorphism was examined in
      the Portuguese population, discriminating between North, Centre and South
      inhabitants. All data were obtained at high-resolution level, using sequence
      based typing. The most frequent allele at each locus was A* 020101 (26%), B*
      440301 and B* 510101 (12% each) and DRB1* 070101 (15%). The predominant three
      locus haplotype was A*020101-B*440301-DRB1*070101 (3.1%), highly frequent in
      North Portugal (5.4%), lower in Centre (2%) and absent in the South. The present
      study demonstrates that the Portuguese population has been genetically influenced
      by Europeans and North Africans, via several historic immigrations. North
      Portugal seems to concentrate, probably due to the pressure of Arab expansion, an
      ancient genetic pool originated from several North Africans and Europeans,
      influences throughout millenniums. South Portugal shows a North African genetic
      influence, probably of recent origin by means of Berbers accompanying Arab
      expansion. We found that Centre Portugal is the distribution limit of some
      alleles and haplotypes that characterize the North or the South of the country.
      Despite North, Centre and South Portugal not being significantly different in
      allele frequencies, this study shows that HLA allele and haplotype frequencies
      are not homogeneous in the country. North and South Portugal show more similarity
      to North Africans in opposition to Centre which appears closer to Europeans.

PMID- 15982255
TI  - Polymorphism of human leukocyte antigen-DRB1, -DQB1, and -DPB1 genes of Shandong
      Han population in China.
AB  - In the present study, polymerase chain reaction-sequence-based typing (PCR-SBT)
      was used to analyze human leukocyte antigen (HLA)-DRB1, -DQB1, and -DPB1 alleles
      of 98 unrelated healthy Shandong Han individuals. A total of 60 alleles, in which
      28 in DRB1, 15 in DQB1 and 17 in DPB1 were found. Among the 28 detected DRB1
      alleles, DRB1*150101, DRB1*070101, DRB1*090102, DRB1*120201, and DRB1*080302 were
      commonly observed, with frequencies of 16.3%, 11.2%, 10.2%, 8.2%, and 5.6%,
      respectively. The most predominant DQB1 allele was DQB1*030101/0309 with the
      frequency of 20.4%, followed by DQB1*0201/0202 (14.8%), DQB1*0602 (14.3%),
      DQB1*030302 (12.2%), and DQB1*060101/060103 (10.7%). Of the 17 detected DPB1
      alleles, DPB1*0501 was the most frequent allele with the frequency of 37.2%.
      DPB1*020102 (18.4%), DPB1*040101 (11.2%), DPB1*0402 (7.1%), and DPB1*1701 (6.6%)
      were also very frequent alleles. A total of 53 estimated DRB1-DQB1 two-locus
      haplotypes were observed in Shandong Han population, of which DRB1*150101
      DQB1*0602 was the most predominant, followed by DRB1*090102-DQB1*030302,
      DRB1*070101-DQB1*0201/0202 DRB1*120201-DQB1*030101/0309, and DRB1*080302-
      DQB1*060101/060103. The distribution of the HLA class II alleles and haplotypes
      frequencies as well as the dendrogram showed that the Shandong Han population
      belongs to the northern group of Chinese. The data have implications for
      anthropological studies and disease associations.

PMID- 15982256
TI  - Maternal - offspring HLA-DRB1 compatibility in multiple sclerosis.
AB  - Major histocompatibility complex (MHC) compatibility has been reported to
      facilitate the long-term tolerance of fetal or maternally derived stem cells
      exchanged during pregnancy. Furthermore, such compatibility has been suggested to
      play a role in fetal viability. An increase in maternal - fetal human leukocyte
      antigen (HLA) compatibility for class II DR alleles has previously been observed
      in the autoimmune disease scleroderma. Here, we examined the hypothesis that
      increased maternal - fetal MHC class II DR compatibility was associated with
      multiple sclerosis (MS) risk. HLA-DRB1 typing was performed in 2170 affected
      individuals and 2894 unaffected relatives from 1006 families with MS in at least
      two members. We found no evidence for increased HLA compatibility between
      affected individuals and their mothers, compared with unaffected individuals and
      their mothers, nor compared with affected individuals and their fathers. We also
      observed no excess of homozygosity of mothers compared with fathers of
      individuals with MS. In families in which the father shared exactly one allele
      with the mother, we found no excess in transmission of this allele to affected or
      unaffected offspring. These findings do not support a role for an excess maternal
      - fetal HLA-DRB1 compatibility in MS susceptibility.

PMID- 15982257
TI  - HLA-B27 polymorphism in Mumbai, Western India.
AB  - Human leucocyte antigen (HLA)-B27 encompasses an increasing number of subtypes
      that show diverse racial/ethnic prevalence in the world. One thousand-one-hundred
      and seventy unrelated individuals from Mumbai, Maharashtra, Western India were
      typed for HLA-B27 antigen by serological methods. HLA-B27 positivity was
      confirmed by polymerase chain reaction using sequence specific primers. High
      resolution typing using sequence specific primers for HLA-B27 alleles (B*2701 -
      B*2721) was carried out in 70 HLA-B27-positive individuals. The frequency of B27
      ranged between 1.48 and 9.6% among the caste groups studied. HLA-B27 subtyping
      identified B*2702 (1.43%), B*2704 (14.29%), B*2705 (70%), B*2707 (12.86%) and
      B*2718 (1.43%), respectively. The findings illustrate substantial genetic
      variation and heterogeneity within population groups from India. Extensive
      subtyping in other Indian caste groups will be necessary to resolve the
      evolutionary implications of HLA-B27 subtypes and their relationship to disease
      association in the Indian context.

PMID- 15982258
TI  - Four new HLA class I alleles in Cauacasoids.
AB  - Four new HLA classical class I alleles in the three loci are described in
      Caucasian individuals. A*3012 was first suspected by an abnormal serologic
      pattern that would be explained by the single amino acid substitution at the A30
      specific Ser17. B*270505 differs from B*270502 in a silent substitution at an up
      to now constant position in the B locus. B*3541 encodes for a new Cys at position
      118 that has not been encountered in neither human nor primate alleles. Cw*0716
      seems to be originated by a large-scale interallelic recombination event between
      Cw*0701/*0706/*0718 and Cw*020202, giving rise to a new antigen-binding cleft
      conformation.

PMID- 15982259
TI  - Identification of a novel HLA-A allele HLA-A*2451 in a Chinese donor.
AB  - A novel human leucocyte antigen-A (HLA-A) allele, A*2451, has been identified
      during routine sequence-specific oligonucleotide typing and sequence-based typing
      of a sample from a registered donor of the Chinese Marrow Donor Program. The
      A*2451 allele differs from the closest matching allele A*2415 by one nucleotide
      substitution in exon 3, nt 363 G-->A, resulting in an amino acid change from M
      ATG to I ATA at codon 121.

PMID- 15982260
TI  - The variation of the novel allele HLA-B*0739 suggests low alloreactivity when
      mismatched with HLA-B*0702.
AB  - We here report the identification of a new HLA-B*07 allele in a male Caucasian.
      The new allele was initially typed as B*0713 by sequence-specific primed PCR.
      Because of the infrequence of that allele, a sequencing-based typing was
      performed to confirm that result. This yielded the detection of the novel allele.
      It is closest to B*070201, while it differs from B*0713 in 12 positions in exon
      2. Compared to B*070201, the new variant is characterized by a non-synonymous
      nucleotide exchange (C-->T) at nucleotide position 118 of exon 2. Previously,
      this was considered a constant position, suggesting that it is likely to be
      caused by a single-point mutation. It results in the amino acid exchange Ala-
      >Val at position 40 of the mature polypeptide. As this position is located in an
      outer loop of the HLA molecule, it is highly unlikely to affect peptide binding
      or T-cell receptor interaction. Thus, the newly found allele should have a low
      alloreactive potential in case of a mismatch to the most common HLA-B allele
      B*0702.

PMID- 15982261
TI  - Bone marrow donor routine HLA typing identified a novel B*55 allele, B*5517,
      confirmed by allele-specific DNA cycle sequencing.
AB  - In this article, we report the identification of a new human leukocyte antigen-B
      allele in a sample that was tested in our routine typing for volunteer bone
      marrow donors. This novel allele officially designed B*5517 was found in a male
      donor of Bavarian Caucasoid origin (Laboratory code 150113). The search for
      unrelated bone marrow donors was initiated by the Aktion Knochenmarkspende
      Bayern. In comparison with the common B*5501 allele, B*5517 differs at three
      nucleotide positions all located in exon 3, at position 379 (C-->G), 419 (T-->A),
      and 420 (A-->C), resulting in two amino acid substitutions at codons 127 and 140.
      The amino acid 127, leucine, is changed to valine, and the amino acid 140, also a
      leucine, is replaced by tyrosine in B*5517.

PMID- 15982262
TI  - A newly identified HLA-C allele: Cw*1210, and confirmation of HLA-Cw*080102.
AB  - HLA-Cw*1210 and -Cw*080102 were identified in Taiwan populations using reverse
      line SSO typing method. Sequencing showed that HLA-Cw*1210 and -Cw*120201/02 were
      identical at exon 2 but differed at exon 3 with three nucleotide substitutions at
      codons 99 and 105 and an amino acid change from tyrosine to phenylalanine at
      codon 99. Also, allele HLA-Cw*080102 differed from HLA-Cw*080101 in exon 3 by a
      single synonymous nucleotide transition at codon 99. HLA-Cw*080102 was found only
      in the Puyuma indigenous tribe of Taiwan and had a frequency of 5%.
      Interestingly, nucleotide substitutions of HLA-Cw*1210 and -Cw*080102 were
      located in a noticeably heterogeneous region of the 5' end of exon 3, where
      similar substitution motifs are frequently found in other HLA-C alleles,
      therefore suggesting preferential gene conversion in this region.

PMID- 15982263
TI  - Identification of a new allele in a Sicilian individual: HLA-DPB1*0302.
AB  - We report here the identification and characterization of a novel human leucocyte
      antigen (HLA)-DPB1 allele that was subsequently named HLA-DPB1*0302 by the WHO
      Nomenclature Committee. HLA-DPB1*0302 was identified in a single Sicilian
      individual by a combination of sequence-specific primers, reverse line sequence
      specific oligonucleotide probing and DNA sequencing-based typing. The DPB1*0302
      allele is most similar to the DPB1*3101 allele, differing by a single mismatch at
      nucleotide position 301 (T to G).

PMID- 15982264
TI  - Identification of a novel HLA-DRB1 allele (HLA-DRB1*111902*).
AB  - In this paper, we report a new HLA-DRB1 allele identified in a male acute myeloid
      leukaemia Chinese patient. This sample was initially typed as DRB1*11XX using
      commercial polymerase chain reaction-sequence-specific primers kit. When it was
      typed using a chip-based sequence-specific oligonucleotide technique, a novel
      hybridization pattern that does not match any known alleles was observed. Through
      sequencing, we have identified this allele as a new HLA-DRB1 allele, which was
      later named HLA-DRB1*111902 by the WHO Nomenclature Committee. The sequence of
      this new allele differs from DRB1*111901 by one nucleotide (from G to C) at 203nt
      of exon 2 but does not cause any amino acid substitution.

PMID- 15982265
TI  - Identification of a new allele, HLA-DRB1*1366*.
AB  - High-resolution polymerase chain reaction sequence-specific primer typing of the
      human leucocyte antigen (HLA)-DRB1 gene of an Italian patient candidate for bone
      marrow transplantation revealed a new allelic variant of HLA-DRB1*13. The
      sequence was named DRB1*1366, and comparison with previously described DRB1
      alleles demonstrated the two closely related sequences were HLA-DRB1*1330 and HLA
      DRB1*130302.

PMID- 15982268
TI  - The effect of environmental tobacco smoke exposure on allergic sensitization and
      allergic rhinitis in adults.
AB  - BACKGROUND: There is only little and furthermore conflicting knowledge about the
      relationship between passive smoking and allergy in adults. In this work, we
      assess the association between exposure to environmental tobacco smoke (ETS) at
      home or at work, and allergic sensitization and allergic rhinitis in 4093 German
      adults. METHODS: Our study population comes from the German National Health
      Survey 1998 of which we analyzed 4093 adults (17-79 years) being non-smokers and
      having complete information on passive smoking and allergy. The association
      between ETS exposure and allergic sensitization and allergic rhinitis was
      assessed using logistic regression models. RESULTS: The effect of ETS exposure on
      allergic sensitization was biggest at the workplace [adjusted OR = 1.17 (0.97,
      1.41)]; the same could be observed with respect to allergic rhinitis [adjusted OR
      = 1.20 (0.96, 1.51)]. There was no effect of ETS exposure at home on both
      allergic sensitization [adjusted OR = 0.99 (0.76, 1.29)] and allergic rhinitis
      [adjusted OR = 1.05 (0.76, 1.43)] in our analysis. CONCLUSIONS: The findings from
      our study show a statistically non-significant tendency that exposure to ETS at
      the workplace increases allergic sensitization and allergic rhinitis in adults.
      This tendency could not be observed with respect to ETS exposure at home.
      PRACTICAL IMPLICATIONS: Exposure to ETS at the workplace should be minimized in
      order to reduce the risk of allergic sensitization, and allergic rhinitis.

PMID- 15982269
TI  - Mouse and cockroach allergens in the dust and air in northeastern United States
      inner-city public high schools.
AB  - Considering that high school students spend a large proportion of their waking
      hours in the school environment, this could be an important location for exposure
      to indoor allergens. We have investigated the levels of mouse and cockroach
      allergens in the settled dust and air from 11 schools in a major northeastern US
      city. Settled dust samples were vacuumed from 87 classrooms, three times
      throughout the school year. Two separate air samples (flow = 2.5 lpm) were
      collected by 53 students over a 5-day period from both their school and their
      home. Mouse allergen (MUP) in the dust varied greatly between schools with
      geometric means ranging from 0.21 to 133 microg/g. Mouse allergen was detectable
      in 81% of the samples collected. Cockroach allergen (Bla g 2) ranged from below
      limit of detection (<0.003 microg/g) to 1.1 microg/g. Cockroach allergen was
      detected (>0.003 microg/g) in 71% of the dust samples. Bla g 2 was detected in
      22% of airborne samples from the schools. By comparison, mouse allergen was only
      detected in 5%. These results indicate that the school may be an important
      location for exposure to allergens from mice and cockroaches and is an indoor
      environment that should be considered in an overall allergen intervention
      strategy. PRACTICAL IMPLICATIONS: To date, cockroach and mouse allergen
      intervention strategies have been mainly focused on the home environment.
      Considering that children spend a significant amount of time in schools, some
      studies have assessed cockroach allergen levels in schools. This study provides a
      clearer picture of the distribution and variability of not only cockroach
      allergen, but also mouse allergen in the school environment. In addition, this
      study describes limitations of personal air sampling in a student population. Our
      results suggest that although cockroach and mouse allergens are commonly
      recovered in classroom dust samples of inner city schools, cockroach allergens
      are recovered in the personal air samples with a greater frequency relative to
      mouse allergens.

PMID- 15982270
TI  - Evaluation of ionic air purifiers for reducing aerosol exposure in confined
      indoor spaces.
AB  - Numerous techniques have been developed over the years for reducing aerosol
      exposure in indoor air environments. Among indoor air purifiers of different
      types, ionic emitters have gained increasing attention and are presently used for
      removing dust particles, aeroallergens and airborne microorganisms from indoor
      air. In this study, five ionic air purifiers (two wearable and three stationary)
      that produce unipolar air ions were evaluated with respect to their ability to
      reduce aerosol exposure in confined indoor spaces. The concentration decay of
      respirable particles of different properties was monitored in real time inside
      the breathing zone of a human manikin, which was placed in a relatively small
      (2.6 m3) walk-in chamber during the operation of an ionic air purifier in calm
      air and under mixing air condition. The particle removal efficiency as a function
      of particle size was determined using the data collected with a size-selective
      optical particle counter. The removal efficiency of the more powerful of the two
      wearable ionic purifiers reached about 50% after 15 min and almost 100% after 1.5
      h of continuous operation in the chamber under calm air conditions. In the
      absence of external ventilation, air mixing, especially vigorous one (900 CFM),
      enhanced the air cleaning effect. Similar results were obtained when the manikin
      was placed inside a partial enclosure that simulated an aircraft seating
      configuration. All three stationary ionic air purifiers tested in this study were
      found capable of reducing the aerosol concentration in a confined indoor space.
      The most powerful stationary unit demonstrated an extremely high particle removal
      efficiency that increased sharply to almost 90% within 5-6 min, reaching about
      100% within 10-12 min for all particle sizes (0.3-3 microm) tested in the
      chamber. For the units of the same emission rate, the data suggest that the ion
      polarity per se (negative vs. positive) does not affect the performance but the
      ion emission rate does. The effects of particle size (within the tested range)
      and properties (NaCl, PSL, Pseudomonas fluorescens bacteria) as well as the
      effects of the manikin's body temperature and its breathing on the ionic purifier
      performance were either small or insignificant. The data suggest that the
      unipolar ionic air purifiers are particularly efficient in reducing aerosol
      exposure in the breathing zone when used inside confined spaces with a relatively
      high surface-to-volume ratio. PRACTICAL IMPLICATIONS: Ionic air purifiers have
      become increasingly popular for removing dust particles, aeroallergens and
      airborne microorganisms from indoor air in various settings. While the indoor air
      cleaning effect, resulting from unipolar and bipolar ion emission, has been
      tested by several investigators, there are still controversial claims (favorable
      and unfavorable) about the performance of commercially available ionic air
      purifiers. Among the five tested ionic air purifiers (two wearable and three
      stationary) producing unipolar air ions, the units with a higher ion emission
      rate provided higher particle removal efficiency. The ion polarity (negative vs.
      positive), the particle size (0.3-3 microm) and properties (NaCl, PSL,
      Pseudomonas fluorescens bacteria), as well as the body temperature and breathing
      did not considerable affected the ionization-driven particle removal. The data
      suggest that the unipolar ionic air purifiers are particularly efficient in
      reducing aerosol exposure in the breathing zone when they are used inside
      confined spaces with a relatively high surface-to-volume ratio (such as
      automobile cabins, aircraft seating areas, bathrooms, cellular offices, small
      residential rooms, and animal confinements). Based on our experiments, we
      proposed that purifiers with a very high ion emission rate be operated in an
      intermittent mode if used indoors for extended time periods. As the particles
      migrate to and deposit on indoor surfaces during the operation of ionic air
      purifiers, some excessive surface contamination may occur, which introduces the
      need of periodic cleaning these surfaces.

PMID- 15982271
TI  - Reduction potential of urban PM2.5 mortality risk using modern ventilation
      systems in buildings.
AB  - Urban PM2.5 (particulate matter with aerodynamic diameter smaller than 2.5
      microm) is associated with excess mortality and other health effects. Stationary
      sources are regulated and considerable effort is being put into developing low
      pollution vehicles and environment-friendly transportation systems. While waiting
      for technological breakthroughs in emission controls, the current work assesses
      the exposure reductions achievable by a complementary means: efficient filtration
      of supply air in buildings. For this purpose infiltration factors for buildings
      of different ages are quantified using Exposures of Adult Urban Populations in
      Europe Study (EXPOLIS) measurements of indoor and outdoor concentrations in a
      population-based probability sample of residential and occupational buildings in
      Helsinki, Finland. These are entered as inputs into an evaluated simulation model
      to compare exposures in the current scenario with an alternative scenario, where
      the distribution of ambient PM2.5 infiltration factors in all residential and
      occupational buildings are assumed to be similar to the subset of existing
      occupational buildings using supply air filters. In the alternative scenario
      exposures to ambient PM2.5 were reduced by 27%. Compared with source controls, a
      significant additional benefit is that infiltration affects particles from all
      outdoor sources. The large fraction of time spent indoors makes the reduction
      larger than what probably can be achieved by local transport policies or other
      emission controls in the near future. PRACTICAL IMPLICATIONS: It has been
      suggested that indoor concentrations of ambient particles and the associated
      health risks can be reduced by using mechanical ventilation systems with supply
      air filtering in buildings. The current work quantifies the effects of these
      concentration reductions on population exposures using population-based data from
      Helsinki and an exposure model. The estimated exposure reductions suggest that
      correctly defined building codes may reduce annual premature mortality by
      hundreds in Finland and by tens of thousands in the developed world altogether.

PMID- 15982272
TI  - A comparison of airborne ergosterol, glucan and Air-O-Cell data in relation to
      physical assessments of mold damage and some other parameters.
AB  - We report here a comparison of long duration air samples in 110 homes where the
      material collected on open faced filter cassettes was analyzed for beta 1,3-d
      glucan, ergosterol, cholesterol and endotoxin. These data were then compared to
      careful estimates of visible mold and Air-O-Cell data. All the values found
      except cholesterol were of a similar magnitude to values reported in the limited
      number of studies available. Glucan was measured with a factor G based assay of
      the Limulus Amebocyte Lysate followed by size exclusion chromatography. This
      showed that the majority of airborne glucan found in these houses was fungal in
      origin arising from both yeasts and intact spores, as well as hyphal and spore
      fragments. Hyphal and spore fragments together represented 16% of the intact
      spore counts but over a broad range. Correlations between airborne glucan were
      strong for ergosterol and visible mold. However, airborne ergosterol was more
      highly correlated to visible mold than glucan. Endotoxin and Air-O-Cell
      measurements were poorly or not related to the other measures in the study. This
      study provides confidence that long duration air samples of the toxin glucan and
      ergosterol are related to building damage. PRACTICAL IMPLICATIONS: Some studies
      of damp buildings have shown a relationship between extent of water/mold damage
      and symptoms. This study compared long duration air samples for glucan and
      ergosterol to extent of visible mold in houses measuring also the nature of the
      glucans present. Both measures were highly correlated to extent of visible mold
      damage in the houses; ergosterol was somewhat superior. Spore counts or
      prevalence of Asp/Pen in Air-O-Cell samples was not related to extent of visible
      mold damage but the observation of hyphal fragments was more likely when mold
      damage was present. This indicates that rigorous assessment of mold damage is a
      useful measure.

PMID- 15982273
TI  - Indoor air pollution in old people's homes related to some health problems: a
      survey study.
AB  - The present research reports on a survey of 96 subjects between the ages of 60
      and 95 years, living close to Paris in a social collective habitat. The aim was
      to show, using goodness-of-fit statistical tests (P < 0.1), how old people
      lifestyles can subject them to generated chemical or bacteriological indoor
      pollutants. Risk factors due to lifestyles were analyzed in relation to
      complaints and to health condition. There are many ways that old people are
      exposed to pollutants: difficulty in maintaining the residence, preference for
      staying in the kitchens, substantial use of cleaning chemicals. However, the
      principal risk for health problems is arguably inadequate ventilation (unclean
      screens, blocked air vents, etc.), which increases the concentration of indoor
      pollutants. These risks are amplified by ignorance about the hazards of
      inadequate ventilation. PRACTICAL IMPLICATIONS: The present investigation
      suggests that the lifestyle and the behavior of old people could be the cause of
      an interior air pollution of their housing. Measures realized in representative
      dwellings selected in relation to results must confirm that these risks would
      require the installation of an automatic monitoring system of the indoor air near
      these people.

PMID- 15982274
TI  - Association between ventilation rates in 390 Swedish homes and allergic symptoms
      in children.
AB  - The aim of the study was to test the hypothesis that a low-ventilation rate in
      homes is associated with an increased prevalence of asthma and allergic symptoms
      among children. A total of 198 cases (with at least two of three symptoms:
      wheezing, rhinitis, eczema) and 202 healthy controls, living in 390 homes, were
      examined by physicians. Ventilation rates were measured by a passive tracer gas
      method, and inspections were carried out in the homes. About 60% of the multi
      family houses and about 80% of the single-family houses did not fulfill the
      minimum requirement regarding ventilation rate in the Swedish building code (0.5
      air changes per hour, ach). Cases had significantly lower ventilation rates than
      controls and a dose-response relationship was indicated. PRACTICAL IMPLICATIONS:
      A low-ventilation rate of homes may be a risk factor for allergies among
      children. Families with allergic children should be given the advice to have good
      ventilation in the home. In investigations, of associations between environmental
      factors and allergies, the air change rate in homes has to be considered.

PMID- 15982275
TI  - Using large eddy simulation to study particle motions in a room.
AB  - As people spend most of their time in an indoor environment, it is important to
      predict indoor pollutant level in order to assess health risks. As particles are
      an important pollutant indoors, it is of great interest to study the airflow
      pattern and particle dispersion in buildings. This study uses large eddy
      simulation (LES) to predict three-dimensional and transient turbulent flows and a
      Lagrangian model to compute particle trajectories in a room. The motion of three
      different types of solid particles in a decaying homogeneous isotropic turbulent
      airflow is calculated. By comparing the computed results with the experimental
      data from the literature, the computational method used in this investigation is
      found to be successful in predicting the airflow and particle trajectories in
      terms of the second-order statistics, such as the mean-square displacement and
      turbulent intensity. This Lagrangian model is then applied to the study of
      particles' dispersion in a ventilated cavity with a simplified geometry for two
      ventilation scenarios. It is shown that light particles follow the airflow in the
      room and many particles are exhausted, while heavier particles deposit to the
      floor or/and are exhausted. PRACTICAL IMPLICATIONS: The results of this paper can
      be used to study dispersion of infectious diseases in enclosed spaces in which
      virus or bacteria are often attached to particles and transported to different
      rooms in a building through ventilation systems. In most of studies, the virus or
      bacteria have been considered to be gaseous phase so there is no slip between
      virus/bacteria and air. The results in this paper show that heavier particles are
      submitted to gravity and are sensitive to the ventilation strategy.

PMID- 15982276
TI  - Novel insight into VOC removal performance of photocatalytic oxidation reactors.
AB  - A general model has been developed for analyzing the removal of volatile organic
      compounds (VOCs) by photocatalytic oxidation (PCO) reactors, taking into
      consideration of the photocatalytic (surface) reaction and the convective mass
      transfer coefficients including allowance for their spatial dependence. On this
      basis, a novel insight into VOC removal performance of PCO reactors is presented.
      The key parameter for evaluating PCO reactor VOC removal performance is the
      number of the mass transfer unit (NTU(m)), which is shown to be a simple linear
      product of three dimensionless parameters: the ratio of the reaction area to the
      cross-sectional area of the flow channel (A*), the Stanton number of mass
      transfer (St(m)), and the reaction effectiveness (eta). The A* represents the
      geometric and structural characteristic of a PCO reactor. The St(m) shows the
      synergistic degree of alignment between the fluid and mass flow fields, and
      reflects the convective mass transfer rate of the reactor. The eta, describes the
      relative intensity between the PCO reaction rate and the mass transfer rate. By
      using the relationship and the parameters, the influence of various factors on
      the VOC removal performance, the bottleneck for improving the performance and
      design of a PCO reactor can be determined. Three examples are used to illustrate
      the application of our proposed model. It is found that the VOC removal
      bottleneck is the reaction rate for honeycomb type reactor, while mass transfer
      rate for light-in-tube type reactor. With six fins the fractional conversion of a
      light-in-tube reactor increases about 70% relative to the one without any fins.
      PRACTICAL IMPLICATIONS: Indoor air quality problem caused by volatile organic
      compounds (VOCs) have annoyed people for many years. Photocatalytic oxidation
      (PCO) appears to be a promising technique for destroying VOCs in indoor air. With
      the model and the novel insight presented in this paper, the influence of various
      factors on the VOC removal performance can be determined. And the bottleneck for
      improving the performance of a PCO reactor can be easily identified. These are
      helpful for designing high performance PCO reactors and optimizing their
      operative performance.

PMID- 15982279
TI  - Disposable magnetically levitated centrifugal blood pump: design and in vitro
      performance.
AB  - A magnetically levitated (MagLev) centrifugal blood pump (CBP) with a disposable
      pump head has been designed to realize a safe, easy-to-handle, reliable, and low
      cost extracorporeal blood pump system. It consisted of a radial magnetic-coupled
      driver with a magnetic bearing having a two-degree freedom control and a
      disposable pump head unit with a priming volume of 24 mL. The easy on-off
      disposable pump head unit was made into a three-piece system consisting of the
      top and bottom housings, and the impeller-rotor assembly. The size and weight of
      the disposable pump unit were 75 mm x 45 mm and 100 g, respectively. Because the
      structure of the pump head unit is easily attachable and removable, the gap
      between the electromagnets of the stator and the target material in the rotor
      increased to 1.8 mm in comparison to the original integrated bearing system of
      1.0 mm. The pump performance, power requirements, and controllability of the
      magnetic bearing revealed that from 1400 to 2400 rpm, the pump performance
      remained fairly unchanged. The amplitudes of the X- and Y-axis rotor oscillation
      increased to +/- 24 microm. The axial displacement of the rotor, 0.4 mm, toward
      the top housing was also observed at the pump rpm between 1400 and 2400. The
      axial and rotational stiffness of the bearing were 15.9 N/mm and 4.4 Nm/rad,
      respectively. The MagLev power was within 0.7 Watts. This study demonstrated the
      feasibility of a disposable, magnetically suspended CBP as the safe, reliable,
      easy-to-handle, low-cost extracorporeal circulation support device.

PMID- 15982280
TI  - The PediPump: a new ventricular assist device for children.
AB  - Options for mechanical circulatory support for the treatment of end-stage heart
      failure in children are limited. Ventricular assist devices (VADs), which have
      revolutionized cardiac care in adults, remain largely unavailable for pediatric
      applications. The PediPump is a new rotary dynamic VAD designed to provide
      support for the entire range of patient sizes encountered in pediatrics. Despite
      being much smaller than currently available VADs, which makes it suitable for
      even newborn circulatory support, the PediPump demonstrates excellent hemodynamic
      performance.

PMID- 15982281
TI  - A validated computational fluid dynamics model to estimate hemolysis in a rotary
      blood pump.
AB  - A major part of developing rotary blood pumps requires the optimization of
      hemolytic properties of the entire pump. Application of a suited computational
      fluid dynamics (CFD)-based hemolysis model allows approximation of blood damage
      in an early phase of the design process. Thus, a drastic reduction of time- and
      cost- intensive hemolysis experiments can be achieved. For the MicroDiagonal Pump
      (MDP), still under development at Helmholtz-Institute in Aachen, Germany,
      different pump configurations have been analyzed, both numerically and
      experimentally. The CFD model of the pump has been successfully validated based
      on the comparison of the pressure head curves (H-Q curves), as discussed in a
      prior publication. In the present study, the authors focus on the development of
      a semiempiric blood damage model using the CFD and in vitro hemolysis data. On
      the one hand, mean key characteristics (shear stress and exposure time) and other
      characteristics affecting blood damage have been calculated based on numerical
      data. On the other hand, in vitro hemolysis tests have been accomplished in order
      to determine the hemolytic curves of two different pump configurations (with the
      same impeller but different tip clearances). Finally, a new function based on a
      general power law has been defined by means of the mean key characteristics. The
      unknown constants of the function have been determined by multidimensional
      regression analysis using the hemolytic curves. For the final validation of this
      new blood damage model, the calculated and the in vitro obtained hemolysis
      indices at the specific VAD operating point have been compared for all pump
      configurations. The comparison showed an excellent agreement, both qualitatively
      and quantitatively.

PMID- 15982282
TI  - Heparin influences human platelet behavior in cardiac surgery with or without
      cardiopulmonary bypass.
AB  - The objective was to investigate whether the platelet dysfunction in cardiac
      surgery is caused by hemodilution or by shear stress due to cardiopulmonary
      bypass (CPB). Platelet count and function were prospectively analyzed in two
      groups of patients undergoing cardiac surgery either with or without CPB (n =
      40). In the first study (n = 20; 10 patients with and 10 without CPB), platelet
      counts were assessed at seven time points. In the second study (n = 20; 10
      patients with and 10 without CPB), platelet function was studied with platelet
      aggregometry at different points during surgery: (a) after induction of
      anesthesia; (b) after sternotomy; and (c) 1 h after heparin. In the first study,
      the CPB group showed a significant decrease in platelet count starting after
      sternotomy (230 +/- 34 vs. 182 +/- 25, P < 0.05) and a maximum decrease at day 1
      postoperative (96 +/- 34, P < 0.05). A similar observation was made in the non
      CBP group. In the second study, a significant decrease of ADP (54 +/- 13% vs. 38
      +/- 9%, P < 0.05), AA (76 +/- 16% vs. 22 +/- 14%, P < 0.05), and Collagen (66 +/-
      13% vs. 37 +/- 11%, P < 0.05) induced platelet aggregation was observed at MOMENT
      d compared to the beginning of surgery in the CPB group. In the non-CBP group a
      significant decrease was observed in AA-induced platelet aggregation at MOMENT d
      (83% +/- 4 vs. 44% +/- 14, P < 0.05). The reduction in platelet count is similar
      with or without cardiopulmonary bypass and is due to pure hemodilution. Platelet
      function reduces significantly after heparin administration. Hemodilution and
      predominantly heparin are the causes of platelet dysfunction after cardiac
      surgery.

PMID- 15982283
TI  - Measurement of the rotor motion and corresponding hemolysis of a centrifugal
      blood pump with a magnetic and hydrodynamic hybrid bearing.
AB  - This study proposed a centrifugal blood pump with a novel magnetic and
      hydrodynamic hybrid passive bearing, which consisted of a plain journal bearing
      for radial stability and a permanent magnetic bearing for axial and tilting
      stability. We measured the radial motion of the bearing and performed hemolysis
      tests for the different radial clearance sizes. In the results, it appeared that
      the radial motion had two modes: the stable center mode, in which the radius of
      the radial motion rapidly converged to less than 20 microm; and the unstable
      circle mode, in which the rotor suspension linearly increased with the rotation
      speed. It also appeared that the pumps with the radial clearance of 80 microm
      caused more hemolysis than with the smaller clearance sizes in the circle mode.
      The circle mode was avoidable by the higher rotation or the asymmetric pump
      structure, but the mechanism of hemolysis in this mode was still unclear.

PMID- 15982284
TI  - A portable cardiopulmonary bypass/extracorporeal membrane oxygenation system for
      the induction and reversal of profound hypothermia: feasibility study in a Swine
      model of lethal injuries.
AB  - The Cleveland Clinic Foundation's (CCF) cardiopulmonary bypass/extracorporeal
      membrane oxygenation (CPB/ECMO) system capabilities were tested in a hypothermia
      trauma management feasibility study in a porcine animal model at the Uniformed
      Services University of the Health Sciences (USUHS, Bethesda, MD, U.S.A.). In this
      survival series, the CCF system was used in a simulated forward lines combat
      casualty application where lethal uncontrolled hemorrhage from major vascular
      injuries was repaired under a state of profound hypothermic arrest (suspended
      animation), followed by recovery and monitoring in an intensive care unit (ICU)
      setting. The animals were monitored for survival, neurological impact, cognitive
      functions, organ damage, and delayed complications over 3 weeks. A survival rate
      of 83% matched rates previously found using conventional equipment. Neurological
      findings, organ dysfunction, and complication rates also were no different from
      previous studies using standard equipment. Successful survival results
      demonstrated that the CCF CPB/ECMO system could be used to induce a period of
      profound hypothermic arrest for the repair of lethal traumatic injuries. The
      logistical advantages of this system make it an attractive choice for use in
      austere settings and during transport.

PMID- 15982285
TI  - A complete mock circulation loop for the evaluation of left, right, and
      biventricular assist devices.
AB  - A new mock circulation loop was developed to replicate the necessary features of
      the systemic and pulmonic circulatory systems, including pulsatile left and right
      ventricles coupled with vascular compliances and resistances. A brief description
      of the mock loop construction is provided before results are presented confirming
      the recreation of perfusion rates and pressures found in the natural systemic and
      pulmonic vascular trees for a normal and failing heart at rest. This rig provides
      the ability to evaluate the hemodynamic effect of left, right, and biventricular
      assist devices in vitro. The small and compact mock circulation rig has the
      potential to reduce device evaluation costs by simulating the natural circulatory
      system, thus providing valuable device performance feedback prior to expensive in
      vivo animal trials.

PMID- 15982286
TI  - Evaluation of left ventricular assist device performance and hydraulic force in a
      complete mock circulation loop.
AB  - Centrifugal pump performance characteristics are vital in determining the ability
      of a prototype left ventricular assist device (LVAD) to meet the physiological
      circulation requirements of the cardiovascular system. These characteristics
      influence the static hydraulic forces encountered by the pump impeller, which
      determine the required load stiffness of suspension type bearings to minimize
      impeller touchdown. Performance investigations were conducted on an LVAD design
      while characterizing the impeller static hydraulic forces of various
      impeller/volute configurations. The pumps were inserted into a complete systemic
      and pulmonary mock circulation rig configured to provide suitable nonpulsatile or
      simulated pulsatile left heart failure environments. The single volute and closed
      shroud impeller configuration exhibited lowest radial (0.01 N) and axial (3 N)
      force at nonpulsatile design flow conditions, respectively. Normal hemodynamic
      conditions of 5.1 L/min at 94 mm Hg were re-established upon inserting the device
      into the left heart failure environment, where the pump operated along the
      nonpulsatile characteristic curve for 2200 rpm. The operational limits on this
      curve were dictated by the required pressure differential across the pump during
      systolic and diastolic periods. The reduction of left atrial pressure (25 to 8 mm
      Hg) indicated the alleviation of pulmonary congestion. The ability for the LVAD
      to support circulation in a left heart failure environment was successfully
      demonstrated in the mock circulation loop. The impeller hydraulic force
      characteristics attained will aid the bearing designer to select the best volute
      and impeller configuration to minimize impeller touchdown in magnetic,
      hydrodynamic or mechanical type bearing applications.

PMID- 15982287
TI  - Numerical and experimental analysis of an axial flow left ventricular assist
      device: the influence of the diffuser on overall pump performance.
AB  - Thousands of adult cardiac failure patients may benefit from the availability of
      an effective, long-term ventricular assist device (VAD). We have developed a
      fully implantable, axial flow VAD (LEV-VAD) with a magnetically levitated
      impeller as a viable option for these patients. This pump's streamlined and
      unobstructed blood flow path provides its unique design and facilitates
      continuous washing of all surfaces contacting blood. One internal fluid
      contacting region, the diffuser, is extremely important to the pump's ability to
      produce adequate pressure but is challenging to manufacture, depending on the
      complex blade geometries. This study examines the influence of the diffuser on
      the overall LEV-VAD performance. A combination of theoretical analyses,
      computational fluid (CFD) simulations, and experimental testing was performed for
      three different diffuser models: six-bladed, three-bladed, and no-blade
      configuration. The diffuser configurations were computationally and
      experimentally investigated for flow rates of 2-10 L/min at rotational speeds of
      5000-8000 rpm. For these operating conditions, CFD simulations predicted the LEV
      VAD to deliver physiologic pressures with hydraulic efficiencies of 15-32%. These
      numerical performance results generally agreed within 10% of the experimental
      measurements over the entire range of rotational speeds tested. Maximum scalar
      stress levels were estimated to be 450 Pa for 6 L/min at 8000 rpm along the blade
      tip surface of the impeller. Streakline analysis demonstrated maximum fluid
      residence times of 200 ms with a majority of particles exiting the pump in 80 ms.
      Axial fluid forces remained well within counter force generation capabilities of
      the magnetic suspension design. The no-bladed configuration generated an
      unacceptable hydraulic performance. The six-diffuser-blade model produced a flow
      rate of 6 L/min against 100 mm Hg for 6000 rpm rotational speed, while the three
      diffuser-blade model produced the same flow rate and pressure rise for a
      rotational speed of 6500 rpm. The three-bladed diffuser configuration was
      selected over the six-bladed, requiring only an incremental adjustment in
      revolution per minute to compensate for and ease manufacturing constraints. The
      acceptable results of the computational simulations and experimental testing
      encourage final prototype manufacturing for acute and chronic animal studies.

PMID- 15982291
TI  - Do smoking, obesity, and stress cause psoriasis?

PMID- 15982292
TI  - In defense of skin.

PMID- 15982294
TI  - Human papillomaviruses associated with epidermodysplasia verruciformis in non
      melanoma skin cancers: guilty or innocent?

PMID- 15982296
TI  - The role of toll-like receptors in the pathogenesis and treatment of
      dermatological disease.
AB  - Toll-like receptors (TLR) are crucial players in the innate immune response to
      microbial invaders. These receptors are expressed on immune cells, such as
      monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are
      not only expressed by peripheral blood cells, but their expression has been
      demonstrated in airway epithelium and skin, important sites of host-pathogen
      interaction. Host cells expressing TLR are capable of recognizing conserved
      pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA,
      and their activation triggers signaling pathways that result in the expression of
      immune response genes and cytokine production. As TLR are instrumental in both
      launching innate immune responses and influencing adaptive immunity, regulation
      of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may
      be important in the pathophysiology of these diseases. Furthermore, since TLR are
      vital players in infectious and inflammatory diseases, they have been identified
      as potential therapeutic targets. Indeed, synthetic TLR agonists such as
      imiquimod have already established utility in treating viral pathogens and skin
      cancers. In the future, it seems possible there may also be drugs capable of
      blocking TLR activation and thus TLR-dependent inflammatory responses, providing
      new treatment options for inflammatory diseases.

PMID- 15982297
TI  - Cutaneous defense mechanisms by antimicrobial peptides.
AB  - The skin actively contributes to host defense by mounting an innate immune
      response that includes the production of antimicrobial peptides. These peptides,
      which include but are not limited to the cathelicidin and defensin gene families,
      provide rapid, broad-spectrum defense against infection by acting as natural
      antibiotics and by participating in host cell processes involved in immune
      defense. This review discusses the biology and clinical relevance of
      antimicrobial peptides expressed in the skin. The importance of the epithelial
      contribution to host immunity is evident, as alterations in antimicrobial peptide
      expression have been associated with various pathologic processes.

PMID- 15982298
TI  - C1q: its functions within the innate and adaptive immune responses and its role
      in lupus autoimmunity.
AB  - The complement cascade is a multi-faced effector component of the innate immune
      response. C1q is the recognition component of the classical pathway of complement
      activation. In addition, C1q has been recognized to serve a number of other
      biological functions including a modulating role on cellular functions within the
      adaptive immune response. The importance of C1q to normal immune regulation is
      reflected by the fact that greater than 90% of individuals who have complete
      congenital deficiency of C1q have been observed to develop early-onset
      photosensitive systemic lupus erythematosus (SLE). As a number of single
      nucleotide polymorphisms have been identified in three C1q genes, it is possible
      that more subtle variations in C1q expression could be a risk factor for
      cutaneous LE and SLE. Thus, a more comprehensive delineation of complotype could
      be of increasing clinical importance in the future.

PMID- 15982299
TI  - Expression of an olfactomedin-related gene in rat hair follicular papilla cells.
AB  - Follicular papilla (FP) cells, but not their closely related dermal fibroblasts,
      can maintain hair growth suggesting cell type-specific molecular signals. To
      define the molecular differences between these two cell types, we generated a
      subtraction complementary DNA (cDNA) library highly enriched in FP-specific cDNA.
      Differential screening identified FP-1 as the most abundant cDNA sequence in this
      subtraction library. FP-1 message RNA is highly abundant in cultured rat vibrissa
      FP cells, can be detected at very low levels in the stomach and the ovary, and is
      undetectable in cultured dermal fibroblasts and in 16 rat non-follicular tissues.
      The full-length, 2.3 kb FP-1 cDNA encodes a protein of 549 amino acids harboring
      a signal peptide, collagen triple helix repeats, and an olfactomedin-like domain.
      Monospecific rabbit antibodies to FP-1 recognize in cultured FP cells a single
      approximately 72 kDa glycoprotein with a approximately 60 kDa protein core. FP-1
      protein is expressed in vivo in a hair cycle-dependent manner, as it can be
      detected in FP during anagen, but not in catagen and telogen phases of the hair
      cycle. FP-1 is presumably a highly specific extracellular matrix protein
      synthesized by FP cells and may be involved in the organization of FP during
      certain phases of normal or pathological hair growth.

PMID- 15982300
TI  - Peptidylarginine deiminase isoforms are differentially expressed in the anagen
      hair follicles and other human skin appendages.
AB  - Peptidylarginine deiminases (PAD) catalyze the conversion of arginine residues to
      citrullines. Five isoforms are known that present distinct tissue locations. In
      the epidermis, like in the skin, only PAD1, 2, and 3 are expressed. Their pattern
      of expression in skin appendages is not known. Here, confocal microscopy analysis
      using highly specific antibodies demonstrated that PAD1 and 3 are expressed in
      human anagen hair follicles, PAD1 and 2, in arrector pili muscles and sweat
      glands, whereas no PAD were detected in sebaceous glands. PAD1 was detected in
      the cuticle and the Huxley layer of the inner root sheath (IRS), and in the
      companion layer. PAD3 was localized in the medulla, and in the three layers of
      the IRS. Using anti-modified citrulline antibodies, we also showed that
      deiminated proteins appeared in the lower part of the IRS, first in the Henle
      layer, then in the cuticle, and finally in the Huxley layer. Our data demonstrate
      that PAD3 is the enzyme that deiminates trichohyalin in the medulla and the Henle
      layer, indicate that PAD1 and 3 are involved in the hair follicle program of
      differentiation, and suggest a role for PAD1 and 2 in the physiology of sweat
      glands and arrector pili muscles.

PMID- 15982301
TI  - A guide to assessing damage response pathways of the hair follicle: lessons from
      cyclophosphamide-induced alopecia in mice.
AB  - After chemical, biological, or physical damage, growing (i.e. anagen) hair
      follicles develop abnormalities that are collectively called hair follicle
      dystrophy. Comparatively lower follicular damage induces the "dystrophic anagen"
      response pathway (=prolonged, dystrophic anagen, followed by severely retarded
      follicular recovery). More severe follicular damage induces the dystrophic
      catagen pathway (=immediate anagen termination, followed by a dystrophic,
      abnormally shortened telogen and maximally fast follicular recovery). In order to
      recognize these distinct damage response strategies of the hair follicle in a
      clinical or histopathological context, we have used the well-established C57BL/6J
      mouse model of cyclophosphamide-induced alopecia to define pragmatic
      classification criteria for hair follicle dystrophy (e.g., structure and
      pigmentation of the hair shaft, location, and volume of ectopic melanin granules,
      distension of follicular canal, number of TdT-mediated dUTP nick end labeling
      positive keratinocytes in the hair bulb; neural cell-adhesion molecule
      immunoreactivity and alkaline phosphatase activity as markers for the level of
      damage to the follicular papilla). These classification criteria for hair
      follicle dystrophy are useful not only in chemotherapy-induced alopecia models,
      but also in the screening of drug-treated or mutant mice in a highly
      standardized, accurate, sensitive, reproducible, easily applicable, and
      quantifiable manner.

PMID- 15982302
TI  - p63-specific activation of the BPAG-1e promoter.
AB  - p63, a member of the p53 superfamily, is an essential cell fate determinant for
      stratified epithelium. Deficiency of p63 leads to lack of differentiated
      epithelium from the skin and the presence of trace undifferentiated cells left in
      the dermis. We found that transcriptionally active isoforms of p63, TAp63beta and
      TAp63gamma, activated the skin-specific promoter of bullous pemphigoid antigen 1
      (BPAG-1). The p63-response element was localized between bases -177 and -153
      upstream of exon 1 in the BPAG-1e promoter, whereas regions surrounding the
      response element suppressed transcriptional responses to p53 and TAp73beta,
      resulting in p63-specific activation of the promoter. This represents a novel
      molecular mechanism by which target gene induction by p63 is distinguished from
      induction by other p53 family members.

PMID- 15982303
TI  - Cigarette smoking, body mass index, and stressful life events as risk factors for
      psoriasis: results from an Italian case-control study.
AB  - We conducted a case-control study to analyse the association of psoriasis of
      recent onset with smoking habits, body mass index (BMI) and stressful life
      events. Cases (n=560; median age 38) were patients with a first diagnosis of
      psoriasis and a history of skin manifestations of no longer than two years after
      the reported disease onset. Patients with a new diagnosis of skin diseases other
      than psoriasis (n=690; median age 36) were selected as controls. The risk of
      psoriasis was higher in ex- and current smokers than in never-smokers, the
      relative risk estimates (OR) being 1.9 for ex-smokers and 1.7 for smokers.
      Smoking was strongly associated with pustular lesions (32 patients, OR=5.3 for
      smokers). The frequency of psoriasis varied significantly in relation to a family
      history of psoriasis in first degree relatives, BMI (OR=1.6 and 1.9 for over
      weighted, BMI 26-29, and obese, BMI >/= 30, respectively) and stressful life
      event score (compared to the lower index quartile, the OR being 2.2 for index
      values >/=115). Risk estimates, when taking into consideration the combined
      effect of these factors with smoking habits, were consistent with a
      multiplicative model of risk combination with no significant statistical
      interaction.

PMID- 15982304
TI  - Pharmacokinetics of 0.1% tacrolimus ointment after first and repeated application
      to adults with moderate to severe atopic dermatitis.
AB  - The systemic exposure to tacrolimus after first and repeated application of 0.1%
      tacrolimus ointment was investigated in 32 adults with moderate to severe atopic
      dermatitis. Patients were allocated to treatment groups according to the size of
      the affected area to be treated: Group 1</=3000 cm(2) (N=11); Group 2>3000
      cm(2)</=6000 cm(2) (N=12); Group 3>6000 cm(2)</=10,000 cm(2) (N=9). Ointment was
      applied twice daily for 13 d and once daily on Day 14; the size of application
      area remained the same irrespective of healing. Blood samples were collected on
      Days 1 (first application), 4, and 14 (last application) and analyzed by a
      validated HPLC-MS/MS method. Systemic exposure to tacrolimus was generally low
      with 96% of blood samples assayed containing concentrations below 1 ng per mL and
      23% of samples below the lower limit of quantification (0.025 ng per mL). Peak
      concentrations after first ointment application were </=2.8 ng per mL, and the
      mean area under the concentration-time curve between 0 and 12 h using the
      trapezoidal rule (AUC(0-12)) values were 1.1, 1.6, and 4.8 ng h per mL for Groups
      1, 2, and 3, respectively. The corresponding mean values on Day 14 were similar
      indicating negligible systemic accumulation of tacrolimus after repeated ointment
      applications. Both the rate and extent of topical absorption decreased as the
      skin lesions healed.

PMID- 15982305
TI  - Hypertrophic scar cells fail to undergo a form of apoptosis specific to
      contractile collagen-the role of tissue transglutaminase.
AB  - Failure of apoptosis has been postulated to cause the hypercellularity and thus
      excess scar-tissue formation of hypertrophic scars (HTS). Here, we have examined
      the susceptibility of fibroblasts derived from normal or HTS to apoptosis induced
      during collagen-gel contraction, a wound-healing model. Normal scar (NS)
      fibroblasts underwent significant apoptosis (>40% total) in contractile collagen,
      whereas apoptosis was not detected in HTS cells. This inability was specific to
      apoptosis induced by contractile collagen because apoptosis could be induced
      using diverse modalities. Since chronic fibrotic tissue is known to be
      excessively cross-linked, we next examined whether collagen matrix that had been
      conditioned by HTS fibroblasts became refractory to enzymatic breakdown and
      indeed, found that it is resistant to breakdown by both collagenase D and matrix
      metalloproteinase-2. Newly formed extracellular matrix is stabilized by the
      enzyme, tissue transglutaminase, which we demonstrated to be overexpressed by HTS
      fibroblasts in vivo and in vitro. Reducing tissue transglutaminase activity in
      collagen gels containing HTS fibroblasts permitted induction of apoptosis on gel
      contraction, whereas increasing enzymic activity in NS cell-containing gels
      completely abrogated collagen-contraction-induced-apoptosis. Together, these
      observations show that HTS fibroblasts exhibit resistance to a specific form of
      apoptosis elicited by contraction of collagen gels, and that this phenomenon is
      dependent on excess activity of cell surface tissue transglutaminase.

PMID- 15982306
TI  - Clinical heterogeneity of 1649delG mutation in the tail domain of keratin 5: a
      Japanese family with epidermolysis bullosa simplex with mottled pigmentation.
AB  - Twenty-five- and 22-y-old Japanese women, who are cousins, presented with distal
      skin fragility, widespread small, pigmented macules, and toenail deformity.
      Blisters occurred between the epidermis and the dermis with degeneration of the
      basal cells, suggesting epidermolysis bullosa simplex with mottled pigmentation
      (EBS-MP). Electron microscopy of the pigmented spots demonstrated vacuolization
      of basal cells as well as disturbed junctional structures and incontinence of
      pigmentation. Gene analysis resulted in detection of a heterozygous deletion of a
      guanine nucleotide in exon 9 at position 1649. P25L mutation was not detected in
      either case. It is possible that EBS-MP occurs not only based on the P25L
      mutation of the keratin 5 molecule, but also because of other types of mutations
      of epidermal keratin genes.

PMID- 15982307
TI  - Two new XPD patients compound heterozygous for the same mutation demonstrate
      diverse clinical features.
AB  - Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are both rare autosomal
      recessive disorders with defects in DNA repair. They are usually distinct both
      clinically and genetically but in rare cases, patients exhibit the clinical
      characteristics of both diseases concurrently. We report two new phenotypically
      distinct cases of XP with additional features of CS (xeroderma pigmentosum and
      Cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation
      (G47R) in the XPD gene within the N terminus of the protein. Both patients had
      clinical features of XP and CS but only one fulfilled most criteria for
      diagnosing CS. Unusually, patient 1 developed early skin cancer, in contrast to
      patient 2, who never developed any malignancies. Cells from both these patients
      have repair defects typical of xeroderma pigmentosum complementation group D
      (XPD) cells, but also had the phenotype of uncontrolled DNA breakage found
      specifically in XPD/CS cells and similarly reduced levels of TFIIH. Despite these
      similarities between our two patients, their clinical features are quite
      different and the clinical severity correlates with other cellular responses to
      ultraviolet irradiation.

PMID- 15982308
TI  - Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma
      skin cancers.
AB  - Recent studies suggest a role of cutaneous human papillomaviruses (HPV) in non
      melanoma skin cancer (NMSC) development. In this study viral DNA loads of six
      frequent HPV types were determined by quantitative, type-specific real-time-PCR
      (Q-PCR) in actinic keratoses (AK, n=26), NMSC (n=31), perilesional tissue (n=22),
      and metastases of squamous cell carcinomas (SCC) (n=8) which were previously
      shown to be positive for HPV5, 8, 15, 20, 24, or 36. HPV-DNA loads in AK,
      (partially microdissected) NMSC, and perilesional skin ranged between one HPV-DNA
      copy per 0.02 and 14,200 cell equivalents (median: 1 HPV-DNA copy per 344 cell
      equivalents; n=48). In 32 of the 79 HPV-positive skin biopsies and in seven of
      the eight metastases viral loads were even below the detection limit of Q-PCR.
      Low viral loads in NMSC were confirmed by in situ-hybridization showing only a
      few HPV-DNA-positive nuclei per section. Viral loads in SCC, basal cell
      carcinomas, and perilesional tissue were similar. But, viral loads found in AK
      were significantly higher than in SCC (p=0.035). Our data suggest that
      persistence of HPV is not necessary for the maintenance of the malignant
      phenotype of individual NMSC cells. Although a passenger state cannot be
      excluded, the data are compatible with a carcinogenic role of HPV in early steps
      of tumor development.

PMID- 15982309
TI  - Human papillomavirus gene expression in cutaneous squamous cell carcinomas from
      immunosuppressed and immunocompetent individuals.
AB  - Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have
      been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant
      recipients (OTR) and immunocompetent individuals. Their role in skin cancer
      remains unclear, and previous studies have not addressed whether the viruses are
      transcriptionally active. We have used in situ hybridization to investigate the
      transcriptional activity and DNA localization of HPV. EV-HPV gene transcripts
      were demonstrated in four of 11 (36%) OTR SCC, one of two (50%) IC SCC, and one
      of five (20%) OTR warts positive by PCR. Viral DNA co-localized with E2/E4 early
      region gene transcripts in the middle or upper epidermal layers. Non-EV cutaneous
      HPV gene transcripts were demonstrated in one of five (20%) OTR SCC and four of
      10 (40%) OTR warts. In mixed infections transcripts for both types were detected
      in two of six (33%) cases. Our results provide evidence of EV-HPV gene expression
      in SCC; although only a proportion of tumors were positive, the similarly low
      transcriptional activity in warts suggests this is an underestimate. These
      observations, together with emerging epidemiological and functional data, provide
      further reason to focus on the contribution of EV-HPV types to the pathogenesis
      of cutaneous SCC.

PMID- 15982310
TI  - Anti-fungal activity of cathelicidins and their potential role in Candida
      albicans skin infection.
AB  - Cathelicidins have broad anti-microbial capacity and are important for host
      defense against skin infections by some bacterial and viral pathogens. This study
      investigated the activity of cathelicidins against Candida albicans. The human
      cathelicidin LL-37, and mouse cathelicidin mCRAMP, killed C. albicans, but this
      fungicidal activity was dependent on culture conditions. Evaluation of the fungal
      membrane by fluorescent dye penetration after incubation with cathelicidins
      correlated membrane permeabilization and inhibition of fungal growth. Anti-fungal
      assays carried out in an ionic environment that mimicked human sweat and with the
      processed forms of cathelicidin such as are present in sweat found that the
      cleavage of LL-37 to forms such as RK-31 conferred additional activity against C.
      albicans. C. albicans also induced an increase in the expression of cathelicidin
      in mouse skin, but this induction did not confer systemic or subcutaneous
      resistance as mCRAMP-deficient mice were not more susceptible to C. albicans in
      blood-killing assays or in an intradermal infection model. Therefore,
      cathelicidins appear active against C. albicans, but may be most effective as a
      superficial barrier to infection.

PMID- 15982311
TI  - Migratory Langerhans cells in mouse lymph nodes in steady state and inflammation.
AB  - Dendritic cells cells induce immunity or-in the steady state-maintain peripheral
      tolerance. Little is known in that regard about Langerhans cells. Therefore, we
      investigated migrating Langerhans cells in the steady-state versus inflammation.
      Increased numbers of Langerhans cells, as determined by immunostaining for
      Langerin/CD207, appeared in the lymph nodes in response to a contact allergen.
      Whereas a large proportion of Langerhans cells expressed CD86 in the steady
      state, CD40, and CD80 were found on a smaller percentage. During inflammation,
      more CD40(+), CD80(+), CD274/B7-H1/PD-L1(+), and CD273/B7-DC/PD-L2(+) Langerhans
      cells were found in the lymph nodes, and they expressed higher levels of these
      molecules. CD275/inducible T cell co-stimulator (ICOS) ligand was not detected.
      Langerhans cells in the nodes of contact allergen-treated mice produced more IL
      12p40/70. This correlated with more interferon-gamma being produced by activated
      lymph node T cells. Epicutaneous immunization with ovalbumin under inflammatory
      conditions led to a more vigorous proliferation of antigen-specific CD4 T cells
      in vitro and in vivo as compared with immunization in the steady state. The
      latter modality, however did not induce strong CD4 T cell tolerance in this
      model. Thus, the overall phenotype of Langerhans cells is not an indicator for
      their immunogenic or tolerogenic potential.

PMID- 15982312
TI  - Type I interferons inhibit maturation and activation of mouse Langerhans cells.
AB  - Type I interferons (IFN) have an essential role in antiviral defense, and they
      are produced upon viral infection in a variety of cells. IFN-alpha/beta treatment
      of immature dendritic cells (DC) is known to induce their phenotypic and
      functional maturation, but it remains unclear whether stimulation by this
      cytokine family influences the functions and maturation of Langerhans cells (LC).
      We used highly enriched (>95%) LC directly isolated from BALB/c mouse skin and
      addressed this issue, comparing LC with splenic CD11c(+) DC. Type I IFN-treated
      LC exhibited impaired ability to produce IL-12 and inflammatory cytokines, IL-6
      and TNF-alpha, whereas IL-10 production was not augmented. In splenic DC, the
      production of inflammatory cytokines was rather enhanced by type I IFN treatment.
      With regard to chemokines, in both LC and splenic DC, type I IFN upregulated the
      production of inflammatory chemokines, such as CXCL10, CXCL11, CCL3, CCL4, and
      CCL5. Strikingly, IFN-beta treatment reduced the expression of CD40, CD54, CD80,
      and CD86 on LC, whereas IFN-beta-treated splenic DC showed enhanced expression of
      these molecules. Furthermore, IFN-beta-treated LC had impaired costimulatory
      activity for anti-CD3-induced proliferation of T cells. Finally, treatment with
      IFN-alpha/beta reduced the migratory capacity of LC to CCL21. These results
      indicate that type I IFN inhibit maturation and activation of LC in a direct
      manner. Our observations may provide a novel explanation for the reported
      inability of LC to act as potent antigen-presenting cells in cutaneous and
      mucosal viral infection.

PMID- 15982313
TI  - Cell death-induced activation of epidermal growth factor receptor in
      keratinocytes: implications for restricting epidermal damage in dermatitis.
AB  - Recent findings have implicated Fas/Fas ligand (FasL) in mediating the death of
      keratinocytes in spongiotic lesions. We asked whether dying keratinocytes could
      potentially initiate a protective response of the skin to limit the destruction
      of the epidermis in the spongiotic areas. In addition to apoptosis, treatment of
      keratinocyte cultures in vitro with FasL triggers a profound phoshorylation of
      the epidermal growth factor receptor (EGFR) and of its downstream effectors ERK
      and protein kinase B (PKB/Akt). Using a variety of inhibitors and blocking
      antibodies, we demonstrated that: (i) apoptosis is required for the generation of
      the signal(s) leading to the activation of EGFR, ERK, and Akt; (ii) the
      activation of EGFR, ERK, and Akt by FasL is indeed mediated by its bona fide
      receptor Fas; (iii) the activation of EGFR is essential for the subsequent
      activation of ERK and Akt; and (iv) apoptotic keratinocytes secrete soluble EGFR
      ligands (including amphiregulin) that are processed from membrane-bound proligand
      forms by metalloproteinase(s). Our findings demonstrate a potential mechanism for
      the restriction and repair of spongiotic damage in eczemas.

PMID- 15982314
TI  - Retinoic acid and its 4-oxo metabolites are functionally active in human skin
      cells in vitro.
AB  - Retinoic acid exerts a variety of effects on gene transcription that regulate
      growth, differentiation, and inflammation in normal and neoplastic skin cells.
      Because there is a lack of information regarding the influence of metabolic
      transformation of retinoids on their pharmacologic effects in skin, we have
      analyzed the functional activity of all-trans-, 9-cis-, and 13-cis-retinoic acid
      and their 4-oxo-metabolites in normal human epidermal keratinocytes (NHEKs) and
      dermal fibroblasts using gene and protein expression profiling techniques,
      including cDNA microarrays, two-dimensional gel electrophoresis, and MALDI-MS. It
      was previously thought that the 4-oxo-metabolites of RA are inert catabolic end
      products but our results indicate instead that they display strong and isomer
      specific transcriptional regulatory activity in both NHEKs and dermal
      fibroblasts. Microarray and proteomic analyses identified a number of novel
      genes/gene products that are influenced by RA treatment of NHEKs or fibroblasts,
      including genes for enzymes catalyzing biotransformation of retinoids,
      corticosteroids, and antioxidants and structural and transport proteins known to
      be essential for homeostasis. Our results expand current knowledge regarding
      retinoic acid action within skin cells and the target tissue/cell regulatory
      systems that are important for modulating the physiological and pharmacological
      effects of this important class of dermatological drugs.

PMID- 15982315
TI  - Ultrastructural features of trafficking defects are pronounced in melanocytic
      nevus in Hermansky-Pudlak syndrome type 1.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized
      by oculocutaneous albinism, a bleeding disorder, and ceroid lipofuscinosis in the
      lungs and gut. HPS is genetically heterogeneous and the most common variant, HPS
      type 1, is caused by mutations in HPS1 gene. The protein encoded by HPS1 is
      considered to facilitate the trafficking of melanocyte-specific gene products
      into the premelanosome. We report the ultrastructural findings in a melanocytic
      nevus seen in a 17-y-old Japanese female patient with HPS1 who is a compound
      heterozygote of HPS1 mutations, including a novel mutation. Electron microscopy
      of a pinkish papule corresponding to the melanocytic nevus revealed markedly
      aberrant, immature melanosomes, large membranous structures, and giant
      melanosomes in the vicinity of trans-Golgi network, the characteristic
      abnormalities because of protein trafficking defects in HPS1. These
      ultrastructural features were far more clearly demonstrated in the nevus cells
      than in the epidermal melanocytes. Thus, ultrastructural analysis of nevus cells
      may be an additional diagnostic tool for HPS1 and could give us important clues
      to further understanding of the pathomechanisms of HPS.

PMID- 15982317
TI  - Ultraviolet-B recruits mannose-binding lectin into skin from non-cutaneous
      sources.
AB  - Mannose-binding lectin (MBL) is an integral part of the innate immune system and
      functions as an opsonin by binding to pathogens and certain apoptotic cells to
      promote their uptake by phagocytes. We recently identified an association of low
      producing MBL polymorphisms with adult dermatomyositis (DM). Our model is that
      MBL deficiency leads to a defect in the clearance of apoptotic debris in the
      skin, thereby predisposing to photosensitive autoimmune disease. In this study,
      we sought to determine whether MBL binds within the epidermis, and to determine
      its source, and potential function of this binding. We demonstrated that the MBL
      is present in irradiated, but not in non-irradiated skin, and in irradiated skin
      it is bound to apoptotic keratinocytes (KC). We found that MBL is not made by KC,
      showing indirectly that it comes from an exogenous source, despite the fact that
      other complement components are made by KC and upregulated by ultraviolet
      irradiation. Finally, we demonstrated that non-KC-derived MBL bound to apoptotic
      KC in vitro and increased the uptake of these cells by dendritic cells. We
      hypothesize that MBL may facilitate non-inflammatory clearance of apoptotic
      debris in patients with photosensitive forms of DM.

PMID- 15982318
TI  - Diagnostic utility of immunohistochemistry in morphologically difficult prostate
      cancer: review of current literature.
AB  - Varma M & Jasani B (2005) Histopathology47, 1-16 Diagnostic utility of
      immunohistochemistry in morphologically difficult prostate cancer: review of
      current literatureImmunohistochemistry is widely used to distinguish prostate
      cancer from benign mimics and to establish the prostatic origin of poorly
      differentiated carcinoma. We critically review the recent advances in prostate
      cancer immunohistochemistry, including the introduction of newer basal cell
      markers such as p63 and the discovery of the overexpression of alpha-methylacyl
      coenzyme A racemase (AMACR) in prostate cancer. The description of newer
      urothelial markers to aid the distinction of prostate cancer from urothelial
      carcinoma is also presented together with refinements in the quality control of
      PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical
      marker for prostate cancer, it has significant limitations. These limitations are
      discussed and the need for interpreting AMACR immunoreactivity in the appropriate
      morphological context and in conjunction with basal call markers is emphasized.
      We also describe the utility of an immunohistochemical panel composed of PSA,
      PSAP and high molecular weight cytokeratin for distinguishing poorly
      differentiated prostate cancer from high-grade urothelial carcinoma. A
      morphological differential diagnosis based selection of immunohistochemical
      markers is highlighted as a novel approach in the diagnosis of prostate cancer in
      routine surgical pathology practice.

PMID- 15982316
TI  - Bioluminescent imaging of melanoma in live mice.
AB  - Melanoma is highly resistant to conventional chemotherapeutic agents and novel
      therapeutic approaches are needed. Current animal models of melanoma in animals
      are sub-optimal. The most commonly used homograft model is the B16 mouse
      melanoma. Evaluation of potential melanoma therapies with this model is limited
      by the inaccuracy of caliper measurement of subcutaneous tumors, of counting lung
      nodules in metastasis models, and the indirect nature of "survival" curves when
      studying brain metastases. We have developed and characterized an accurate,
      sensitive, and reproducible bioluminescent B16 melanoma model that allows for
      serial, real-time analyses of tumor burden in live mice. We demonstrate that this
      model is applicable to subcutaneous tumors, lung metastases, and intracranial
      tumors and offers a solution to many of the limitations of previous models. As
      proof of principle, we use this model to show the efficacy of a live, Listeria
      monocytogenes vaccine expressing the melanoma antigen tyrosinase-related protein
      2 to protect mice against intravenous B16 melanoma challenge. Additionally, we
      extend our approach to include the human A375 melanoma model and are able to show
      in vivo differences between sub-lines with varying metastatic potential. These
      models represent an accurate and reproducible means for in vivo melanoma
      monitoring in preclinical studies.

PMID- 15982319
TI  - Tumour budding as prognostic factor in stage I/II colorectal carcinoma.
AB  - AIMS: The term tumour 'budding' has been coined for the detachment of tumour
      cells from the neoplastic glands of adenocarcinomas and is presumed to be an
      early step in the metastatic process. A limited number of studies have shown
      budding to be an adverse prognostic factor. METHODS AND RESULTS: All primary
      single, non-metachronous TNM stage I/II colorectal carcinomas without neoadjuvant
      treatment resected in the years 1994-1999 were included (n = 186). Tumour buds
      were counted in pan-cytokeratin immunostains in a 0.785-mm2 field of vision (250
      x). During follow-up 21 patients had distant metastases and 12 patients died of
      their disease. Budding was determined at 14 and 20.46, median and mean,
      respectively (range 0-120). A cut-off of 25 was found to be sensitive (0.76) and
      specific (0.739). Kaplan-Meier survival analysis showed high budding to be a
      strong adverse prognosticator. By Cox regression, high budding together with
      venous angioinvasion were independent prognostic factors. CONCLUSIONS: This study
      confirms the prognostic value of budding in a contemporary series of colorectal
      carcinomas that by TNM were low risk. Technically easy, rapid and robust to
      determine, budding quantified in pan-cytokeratin stains significantly aids in the
      identification of high-risk patients and is recommended for more general use in
      surgical pathology.

PMID- 15982320
TI  - A novel classification of tumour budding in colorectal cancer based on the
      presence of cytoplasmic pseudo-fragments around budding foci.
AB  - AIMS: Tumour budding is an adverse prognostic factor in colorectal cancer (CRC).
      We have investigated the significance of cytoplasmic fragments occurring in the
      immediate vicinity of tumour budding foci. METHODS AND RESULTS: Seventy-three
      CRCs with high-grade budding (> 10 budding foci in a x 20 objective field) were
      classified according to extent of budding (10-19 versus 20+ foci) and by the
      presence or absence of cytoplasmic fragments identified by immunostaining for
      cytokeratin. In serial sections, cytoplasmic fragments were shown to be dendritic
      cell processes in continuity with budding tumour cells and were renamed pseudo
      fragments. Cytoplasmic pseudo-fragments, but not extent of budding, were
      associated with aberrant expression of beta-catenin (P = 0.045) and laminin-5
      gamma2 (P < 0.0001), and with absent peritumoral lymphocytic infiltration (P =
      0.0077). Cytoplasmic pseudo-fragments had a stronger association with
      infiltrating growth pattern (P = 0.0014) than extent of tumour budding (P =
      0.014). There was no association between extent of budding and cytoplasmic pseudo
      fragments (P = 0.12). CONCLUSIONS: Cytoplasmic pseudo-fragments may be a marker
      for an activated budding phenotype that is associated with cell motility and
      increased invasiveness in CRC and is independent of the extent of budding.

PMID- 15982321
TI  - Demographic and pathological characteristics of serrated polyps of colorectum.
AB  - AIMS: To characterize a series of colorectal polyps, focusing on the
      clinicopathological features of serrated adenoma (SA), mixed polyp (MP) and the
      recently recognized sessile serrated adenoma (SSA). METHODS AND RESULTS: Eight
      hundred and ninety-one conventional adenomas (AD), 298 hyperplastic polyps (HP),
      27 SSA, 10 MP and 24 traditional SA were obtained from patients during
      colonoscopic examination. SSA were more likely to be proximally located than
      other polyps. All SA, MP and SSA and a randomly selected subset of HP (n = 61)
      and ADs (n = 93) were assessed for expression of mucin, MLH1, MGMT, and Ki67. SSA
      expressed more MUC5AC than either HP or SA. Loss of MLH1 was not observed in any
      serrated polyps and in only one AD. Loss of MGMT occurred in 13% of AD, and
      showed no correlation with histological type, size or location. Loss of MGMT
      occurred in 24% of SSA, MP and SA (combined), and was more frequent in proximal
      lesions and larger lesions. SSA had a higher proliferative index than HP. In MP,
      the proliferative index of the non-dysplastic component was closer to HP than
      SSA, while the dysplastic component was intermediate between SA and AD.
      CONCLUSIONS: SSA differ from other serrated polyps of colorectum in terms of
      location, morphology and immunophenotype.

PMID- 15982322
TI  - Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate
      treatment: a potential diagnostic pitfall.
AB  - AIMS: The diagnosis of gastrointesinal stromal tumours (GISTs) is widely based on
      morphological features and KIT (CD117) immunoreactivity. Most patients with
      advanced GISTs show a major clinical response after treatment with imatinib
      mesylate. The histopathological features of GISTs in patients on prolonged
      imatinib treatment have, thus far, not been addressed in detail. In this report,
      we present three patients with metastatic GISTs, who received more than 1 year of
      therapy with imatinib, and whose tumours changed their morphological and
      immunohistochemical characteristics during continued treatment with the drug.
      METHODS AND RESULTS: All three primary GISTs from these patients were classical
      spindle-type tumours, showing diffuse, strong CD117, CD34, and focal alpha-smooth
      muscle actin expression. During treatment, two clinically progressive and one
      clinically stable GIST revealed a diffuse epithelioid, or pseudopapillary
      epithelioid growth pattern, characterized by rounded cells with eosinophilic
      cytoplasm and uniform round-to-ovoid nuclei. In addition, GIST specimens from
      patients on therapy showed complete loss of CD117 immunoreactivity. Remarkably,
      two of these tumours also became CD34 immunonegative and in one case the
      progression was accompanied by desmin expression. KIT mutational analysis
      revealed the presence of distinct exon 11 mutant isoforms in all cases examined,
      while the same genotype was sustained in the base line and on-therapy tumour
      specimens, proving the common origin of analysed specimens. CONCLUSIONS: GISTs
      subject to imatinib treatment can undergo striking (immuno)phenotypic changes,
      which are not necessarily corroborated by new genotypic modifications. Because
      these may mimic other tumour types, this feature creates a differential
      diagnostic challenge, of which the pathologist should be aware.

PMID- 15982323
TI  - Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes,
      testicular carcinoma in situ and germ cell tumours.
AB  - AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and
      pluripotency. Our recent genome-wide gene expression profiling study of the
      precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed
      close similarity between ESC and CIS, including high NANOG expression. In the
      present study we analysed the protein expression of NANOG during normal
      development of human testis and in a large series of neoplastic/dysgenetic
      specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS
      and in CIS-derived testicular tumours with marked differences; seminoma and
      embryonal carcinoma were strongly positive, differentiated somatic elements of
      teratoma were negative. We provide evidence for the fetal origin of testicular
      cancer as we detected strong expression of NANOG in fetal gonocytes up to
      gestational week 20, with subsequent down-regulation occurring earlier than for
      OCT-4. We detected no expression at the protein level in normal testis.
      CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and
      the high level of NANOG along with OCT-4 are determinants of the stem cell-like
      pluripotency of the preinvasive CIS cell. Timing of NANOG down-regulation in
      fetal gonocytes suggests that NANOG may act as a regulatory factor up-stream to
      OCT-4.

PMID- 15982324
TI  - Expression of augmenter of liver regeneration (ALR) in human liver cirrhosis and
      carcinoma.
AB  - AIMS: To determine the expression of a protein termed augmenter of liver
      regeneration (ALR), recently found to have a specific and beneficial effect on
      the process of liver regeneration in normal and diseased human liver. METHODS AND
      RESULTS: ALR expression in normal and cirrhotic human livers with various
      underlying diseases as well as in tissue samples of hepatocellular carcinoma
      (HCC) and cholangiocellular carcinoma (CCC) was analysed by immunohistochemistry
      and quantitative reverse transciptase-polymerase chain reaction (RT-PCR).
      Expression analysis of ALR in total liver protein extracts by Western blotting
      showed mainly dimeric ALR protein. Immunohistochemically, cytosolic and
      perinuclear immunosignals were found in hepatocytes and cholangiocytes in normal,
      cirrhotic or cancerous liver tissue and only weak signals in some endothelial
      cells in normal livers. Quantitative mRNA analysis revealed significantly
      increased ALR expression in cirrhosis compared with normal liver tissue. In HCC
      and CCC ALR mRNA expression was also significantly enhanced compared with normal
      liver tissue, but expression levels did not differ from the matching non
      neoplastic tissue in the same patient. CONCLUSIONS: The findings suggest an
      important role for ALR in hepatocellular regeneration in liver cirrhosis as well
      as in hepatocarcinogenesis and therefore its potential value in the clinical
      diagnosis of hepatic cirrhosis and cancer.

PMID- 15982325
TI  - WT1 expression in angiogenic tumours of the skin.
AB  - AIMS: To determine the expression of WT1 in endothelial proliferations and
      tumours. Endothelial cells are derived from angioblasts which differentiate into
      bone marrow stem cells (BMSC). BMSC are characterized by the constitutive
      expression of the WT1 gene and we have postulated that its expression may be
      maintained during the differentiation of angioblasts to endothelial cells.
      METHODS AND RESULTS: The expression of WT1 was studied in human umbilical vein
      derived (HUVEC) and brain microvascular endothelial cells (HBME) as well as in a
      Kaposi sarcoma (KS) cell line in vitro. Forty-two human skin biopsy samples of
      endothelial proliferations and tumours were analysed for the protein expression
      of WT1 using the monoclonal antibodies for wt-WT1 (6F-H2) and its 17AA+ variant
      (2C12). WT1 expression was detectable in HUVEC and KS cells and all WT1 splice
      variants examined (17AA+/- KTS+/-) were detectable in KS cells, while the 17AA+/-
      and KTS- variants were present in HUVEC. Immunohistochemical analysis of the 42
      human skin biopsy samples revealed cytoplasmic WT1 expression using wild-type
      specific antibody (6FH2) in microvessels, which is maintained during
      neoangiogenesis (inflammation, haemorrhage, peritumoral angiogenesis). Around one
      third of haemangiomas (3/10) and non-HIV-Kaposi sarcomas (7/18) expressed the WT1
      protein in the cytoplasm of tumour cells compared with its frequent expression in
      angiosarcomas (7/8) using the same antibody (6FH2). The nuclear 17AA+ isoform of
      WT1 was detectable at protein level in a small proportion of KS cases exclusively
      (3/7). CONCLUSION: Our data suggest that WT1 protein expression is maintained
      during angiogenesis and malignant transformation of endothelial cells and can be
      considered as a new endothelial marker.

PMID- 15982326
TI  - Comparative study of CD34, alpha-SMA and h-caldesmon expression in the stroma of
      gynaecomastia and male breast carcinoma.
AB  - AIMS: To address the fibroblastic/myofibroblastic nature of stroma in
      gynaecomastia and in male breast carcinoma, the expression of CD34, alpha-smooth
      muscle actin (SMA) and h-caldesmon in the stromal cells was investigated by
      immunohistochemistry. METHODS AND RESULTS: Representative archival paraffin
      blocks were collected from male patients with gynaecomastia (32 cases) and
      mammary carcinoma (24 cases) between 1984 and 2004 and CD34, alpha-SMA and h
      caldesmon were assessed immunohistochemically using a streptavidin-biotin method.
      Thirty cases of gynaecomastia showed a CD34+, alpha-SMA- and h-caldesmon-
      immunophenotype with different CD34 staining intensity in the various
      histological subtypes. Positivity for alpha-SMA and negativity for CD34 and h
      caldesmon was found in a case of florid gynaecomastia relating to reactive
      fibrosis due to previous surgical intervention. Acquisition of alpha-SMA
      expression by stromal fibroblasts but absence of CD34 staining was identified in
      22 cases of male breast carcinoma. CONCLUSIONS: The immunophenotype of periductal
      connective tissue stroma in gynaecomastia appears to parallel the phenotype of
      normal breast stroma. In male breast carcinoma the stromal cell immunophenotype
      is similar to that of its female counterpart showing myofibroblastic
      differentiation. However alpha-SMA+ and CD34- are not specific to malignancy
      because such findings are also encountered in reactive fibrosis.

PMID- 15982327
TI  - IL-6, its receptors and its relationship with bcl-2 and bax proteins in
      infiltrating and in situ human breast carcinoma.
AB  - AIMS: To characterize the expression pattern of IL-6 and its receptors (IL
      6R(alpha) and gp130), to relate this pattern to bcl-2 and bax expression and to
      elucidate the effects on the proliferation/apoptosis equilibrium in benign
      conditions and in situ and infiltrating breast cancer. METHODS AND RESULTS: The
      immunoexpression of IL-6 and its receptors (IL-6R(alpha) and gp130), and their
      relationship with bcl-2 and bax proteins, were studied in in situ and
      infiltrating tumours and in benign breast lesions by means of Western blotting
      and immunohistochemistry. The percentages of samples positive for IL-6, bcl-2 and
      bax and their immunoreaction densities were higher in in situ carcinomas and
      infiltrating tumours than in benign lesions; although in in situ lesions were not
      so high as in infiltrating tumours, except for bax, whose immunoexpression was as
      weak as in benign conditions, resulting in a bcl-2/bax ratio higher than in
      infiltrating tumours. CONCLUSIONS: The high expression of IL-6 and its receptors
      in tumours might be related to the enhanced cell proliferation occurring in
      breast cancer. IL-6 could act by increasing bcl-2 expression and thus altering
      the proliferation/apoptosis balance toward neoplastic cell proliferation. The
      increased bax immunoreactivity observed only in infiltrating tumours, which was
      not so high as the increase in bcl-2 immunoreactivity, might be interpreted as an
      attempt to hinder cell proliferation.

PMID- 15982328
TI  - Extrafollicular proliferation of B cells in the absence of follicular
      hyperplasia: a distinct reaction pattern in lymph nodes correlated with primary
      or recall type responses.
AB  - AIMS: Extrafollicular activation of B cells is rarely observed in human lymph
      nodes. The aim of this study was to extensively analyse the expression of surface
      molecules and transcription factors in four such cases, comparing them with
      follicular B cells and medullary cord plasma cells. METHODS AND RESULTS: Various
      combinations of B-cell-related surface markers and transcription factors were
      studied by triple immunofluorescence. While in the germinal centre, reactive
      immunoglobulin production occurred exclusively in non-proliferating cells, in
      extrafollicular activation proliferation of B cells and immunoglobulin production
      coexisted. In two of these cases proliferating cells were mainly IgG+CD27+, i.e.
      derived from class-switched postgerminal centre memory B cells. Some of these
      cells expressed CD30. In the other two cases, immunoglobulin-forming cells were
      non-class-switched IgM+CD27- B cells, representing a primary expansion of naive B
      cells. CONCLUSIONS: Extrafollicular B-cell activation is the morphological
      correlate of rapid B-cell responses that do not involve the germinal centres. It
      is pathogenetically heterogeneous, comprising primary responses that occur prior
      to, or independent of, germinal centre reaction or memory cell activation in
      recall responses.

PMID- 15982329
TI  - Large B-cell lymphoma with Hodgkin's features.
AB  - AIMS: To describe the features of a series of nine cases of diffuse large B-cell
      lymphoma (DLBCL) showing morphological and immunophenotypic features that are
      intermediate with Hodgkin's lymphoma (HL). METHODS AND RESULTS: Most cases (6/9)
      presented as mediastinal tumours affecting young males, while the other three
      cases arose in extramediastinal locations. Histopathologically, tumours showed
      diffuse large cell areas in a polymorphous background, with pleomorphic cytology
      and the common presence of Hodgkin's and Reed-Sternberg cells.
      Immunophenotypically, tumours shared features of DLBCL and classical HL, with
      expression of CD30, CD15 (6/9), and a full B-cell profile including CD45RB, CD20,
      CD79a and OCT2. Epstein-Barr virus-latent membrane protein expression was found
      in 2/9 cases. The majority of tumours had immunohistochemical features consistent
      with activation of the NF-(kappa)B pathway, including nuclear location of the c
      REL/p65 subunit, overexpression of phosphorylated I(kappa)B(alpha), and
      overexpression of NF-(kappa)B targets. Finally, 2/9 cases showed 3q27 (BCL6)
      rearrangement, and 1/9 had p53 gene mutations, both of which are rarely detected
      in classical HL. CONCLUSIONS: These findings suggest that DLBCLs with HL features
      constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth
      and peculiar characteristics could be facilitated by a particular
      microenvironment found in the mediastinum.

PMID- 15982330
TI  - Atypical ductal hyperplasia in male breast tissue with gynaecomastia.

PMID- 15982331
TI  - Primary extragonadal germ cell tumour: unusual localization of a c-kit mutated
      retroperitoneal seminoma in the gastric wall.

PMID- 15982332
TI  - Paraganglion of the prostate gland: an uncommon mimic of prostate cancer in
      needle biopsies.

PMID- 15982333
TI  - Pseudotumour of renal pelvis: Liesegang rings mimicking a solid neoplasm of the
      renal pelvis.

PMID- 15982334
TI  - CD1a immunopositivity could help to address prognosis of intestinal-type
      Barrett's metaplasia.

PMID- 15982335
TI  - Low-grade intraepithelial neoplasia of Brunner's gland.

PMID- 15982336
TI  - Measurement in histopathology.

PMID- 15982337
TI  - Peritoneal haematopoiesis in acute panmyelosis with myelofibrosis.

PMID- 15982338
TI  - Disseminated Penicillium marneffei infection.

PMID- 15982339
TI  - The role of PFA-100 testing in the investigation and management of haemostatic
      defects in children and adults.
AB  - The PFA-100 provides a simple global measure of high shear-dependent platelet
      function, and as such is not diagnostic or specific to any disorder. Prolonged
      closure times must be interpreted in conjunction with a full blood count, von
      Willebrand factor (VWF) screen and other platelet tests. The PFA-100 may also
      give false negative results with relatively common platelet defects. If clinical
      suspicion is high, further detailed platelet function testing and VWF screening
      are required to exclude abnormal platelet function, even if the PFA-100 is
      normal. In more recent studies the PFA-100 has been used for preoperative
      identification and management of surgical patients with haemostatic defects and
      for assessing the clinical effectiveness of platelet transfusion therapy. This
      review highlights the up to date, evidence-based, advantages and disadvantages of
      the PFA-100 test in the investigation and management of haemostatic disorders in
      both children and adults.

PMID- 15982340
TI  - Red cell pyruvate kinase deficiency: molecular and clinical aspects.
AB  - Red cell pyruvate kinase (PK) deficiency is the most frequent enzyme abnormality
      of the glycolytic pathway causing hereditary non-spherocytic haemolytic anaemia.
      The degree of haemolysis varies widely, ranging from very mild or fully
      compensated forms, to life-threatening neonatal anaemia and jaundice
      necessitating exchange transfusions. Erythrocyte PK is synthesized under the
      control of the PK-LR gene located on chromosome 1. To date, more than 150
      different mutations in the PK-LR gene have been associated with PK deficiency.
      First attempts to delineate the biochemical and clinical consequences of the
      molecular defect were mainly based on the observation of the few homozygous
      patients and on the analysis of the three-dimensional structure of the enzyme.
      More recently, the comparison of the recombinant mutants of human red cell PK
      with the wild-type enzyme has enabled the effects of amino acid replacements on
      the enzyme molecular properties to be determined and help to correlate genotype
      to clinical phenotype.

PMID- 15982341
TI  - Prospective gene expression analysis accurately subtypes acute leukaemia in
      children and establishes a commonality between hyperdiploidy and t(12;21) in
      acute lymphoblastic leukaemia.
AB  - We have prospectively analysed and correlated the gene expression profiles of
      children presenting with acute leukaemia to the Royal London and Great Ormond
      Street Hospitals with morphological diagnosis, immunophenotype and karyotype.
      Total RNA extracted from freshly sorted blast cells was obtained from 84
      lymphoblastic [acute lymphoblastic leukaemia (ALL)], 20 myeloid [acute myeloid
      leukaemia (AML)] and three unclassified acute leukaemias and hybridised to the
      high density Affymetrix U133A oligonucleotide array. Analysis of variance and
      significance analysis of microarrays was used to identify discriminatory genes. A
      novel 50-gene set accurately identified all patients with ALL and AML and
      predicted for a diagnosis of AML in three patients with unclassified acute
      leukaemia. A unique gene set was derived for each of eight subtypes of acute
      leukaemia within our data set. A common profile for children with ALL with an
      ETV6-RUNX1 fusion, amplification or deletion of ETV6, amplification of RUNX1 or
      hyperdiploidy with an additional chromosome 21 was identified. This suggests that
      these rearrangements share a commonality in biological pathways that maintains
      the leukaemic state. The gene TERF2 was most highly expressed in this group of
      patients. Our analyses demonstrate that not only is microarray analysis the
      single most effective tool for the diagnosis of acute leukaemias of childhood but
      it has the ability to identify unique biological pathways. To further evaluate
      its prognostic value it needs to be incorporated into the routine diagnostic
      analysis for large-scale clinical trials in childhood acute leukaemias.

PMID- 15982342
TI  - Interphase fluorescence in situ hybridization with an IGH probe is important in
      the evaluation of patients with a clinical diagnosis of chronic lymphocytic
      leukaemia.
AB  - Translocations involving IGH are common in some lymphoid malignancies but are
      believed to be rare in chronic lymphocytic leukaemia (CLL). To study the clinical
      utility of fluorescence in situ hybridization (FISH) for IGH translocations, we
      reviewed 1032 patients with a presumptive diagnosis of CLL. Seventy-six (7%)
      patients had IGH translocations. Pathology and clinical data were available for
      the 24 patients evaluated at the Mayo Clinic. Ten (42%) patients had IGH/cyclin
      D1 fusion and were diagnosed with mantle cell lymphoma (MCL). The immunophenotype
      was typical of MCL in three of these patients and atypical for MCL in seven
      patients. One patient had biclonal disease with typical MCL and CLL with IGH/BCL
      2. Eleven (46%) patients had IGH/BCL-2 fusion including the patient with biclonal
      disease. Two of these patients had leukaemic phase follicular lymphoma and nine
      patients had CLL. The median progression-free survival of patients with CLL and
      IGH/BCL-2 translocation was 20.6 months. The two patients with IGH/BCL-3 fusion
      (one of these also had IGH/BCL-11a) had rapid disease progression. The IGH
      partner gene was not identified in two patients. We conclude that use of an IGH
      probe in FISH analysis of monoclonal B-cell lymphocytosis improves diagnostic
      precision and could have prognostic value in patients with CLL.

PMID- 15982343
TI  - FLT3 inhibition in t(4;11)+ adult acute lymphoid leukaemia.
AB  - The present study was designed to investigate, in t(4;11)+ adult lymphoid
      leukaemia (ALL) blast cells, the pathogenetic role of the FLT3 protein, its level
      of mRNA and protein expression, the degree of constitutive phosphorylation, the
      possible presence of mutations of the sequence, the capacity of signal
      transduction and the potential therapeutic role of specific inhibitors. We
      evaluated nine adult ALL patients carrying this translocation. The increased FLT3
      mRNA levels, determined by oligonucleotide microarray analysis, was in agreement
      with the increased protein expression evaluated by Western blot. The protein was
      constitutively phosphorylated in all cases analysed. Polymerase chain reaction
      detected no internal tandem duplication or point mutations. The signal
      transduction apparatus, after stimulation with the specific ligand, was
      preserved. We then investigated the effect of specific FLT3 inhibition on signal
      transduction and survival. The PKC412 inhibitor specifically inhibited ligand
      induced phosphorylation; the same inhibitor reduced the survival of leukaemic
      cells when compared with untreated cells. These data indicate that the FLT3
      protein might play a role in this subgroup of ALL with a particularly poor
      prognosis. Specific inhibition of the kinase receptor must be hypothesised as an
      innovative therapeutic tool for t(4;11)+ ALL patients.

PMID- 15982344
TI  - Engraftment of NOD/SCID/gammac(null) mice with multilineage neoplastic cells from
      patients with juvenile myelomonocytic leukaemia.
AB  - Several lines of evidence indicate the clonal nature of juvenile myelomonocytic
      leukaemia (JMML), involving myeloid, erythroid, megakaryocyte and B-lymphoid
      lineages. However, it is unclear whether the T-lymphocyte lineage is involved. We
      demonstrated that cells from six patients with JMML repopulated in non-obese
      diabetic/severe combined immunodeficient/gammac(null) mice and differentiated
      into granulocytes, monocytes, erythrocytes, B lymphocytes, T lymphocytes and
      natural killer cells. The percentage of human CD45 antigen-positive cells ranged
      from 41% to 73% in the murine bone marrow 12 weeks after transplantation. To
      examine the involvement of lymphocyte subpopulations, we purified human CD3(+),
      CD19(+) and CD56(+) cells from murine bone marrow cells transplanted from a
      patient with monosomy 7. Fluorescence in situ hybridization (FISH) showed the
      clonal marker in 96-100% of purified CD3(+), CD19(+) and CD56(+) subpopulations.
      These findings support the concept that JMML originates in transplantable
      multilineage haematopoietic stem cells. This novel murine xenotransplant model
      should be useful for investigating the nature of stem cells and testing new
      therapies for patients with JMML.

PMID- 15982345
TI  - Autocrine/paracrine involvement of insulin-like growth factor-I and its receptor
      in chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long
      lived B lymphocytes blocked in G(0/1) by impaired apoptosis. As insulin-like
      growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell
      types, we investigated whether IGF-I and its receptor (IGF-IR) participate in
      autocrine/paracrine loops affecting the survival of CLL cells. IGF-IR protein and
      mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF-IR
      expression in CLL patients was positively correlated with the expression of the
      antiapoptotic protein Bcl-2 and was involved in CLL cell survival in vitro. Serum
      IGF-I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells
      expressed IGF-I mRNA and secreted the growth factor in vitro. Therefore, local
      production of IGF-I can account for the increased levels of serum IGF-I,
      independently of GH, and may be related to autocrine/paracrine control of
      lymphocyte survival acting at IGF-IR. This is the first demonstration of IGF-IR
      expression in a subgroup of CLL patients and of its antiapoptotic effects in
      vitro, highlighting the importance of this growth factor receptor as a possible
      therapeutic target in CLL.

PMID- 15982346
TI  - Outcome after first relapse in childhood acute lymphoblastic leukaemia - lessons
      from the United Kingdom R2 trial.
AB  - A retrospective analysis of children with first relapse of acute lymphoblastic
      leukaemia (ALL), treated on the UKALL R2 protocol at four different hospitals,
      between June 1995 and December 2002 was performed. Of the 150 children 139 (93%)
      achieved a second complete remission. The overall survival (OS) and event-free
      survival (EFS) for the whole group was 56% and 47% respectively. The duration of
      first complete remission and immunophenotype, but not sites of relapse, were
      predictive for survival. Using the Berlin-Frankfurt-Munster risk stratification
      for relapsed ALL, the OS and EFS for standard, intermediate (IR) and high risk
      (HR) groups were 92% and 92%, 64% and 51%, and 14% and 15%, respectively; P <
      0.0001 for both OS and EFS. In the IR group, those with a very early isolated
      central nervous system relapse also had a significantly worse outcome (P =
      0.0001). Given the poor outcome of a second relapse, clear strategies are
      required to identify those in the IR group who will most benefit from stem cell
      transplantation (SCT). A higher proportion (16%) of induction failures in the HR
      group suggest the need for novel agents during this phase of treatment, but SCT
      was associated with a lower relapse rate and better outcome than those treated
      with chemotherapy alone.

PMID- 15982348
TI  - CD34+ cell selection is required to assess HOXA9 expression levels in patients
      with myelodysplastic syndrome.
AB  - Overexpression of HOXA9 is linked to the molecular pathogenesis of acute myeloid
      leukaemia (AML) and myelodysplastic syndrome (MDS), conferring a poor prognosis.
      HOXA9 expression levels were analysed in the diagnostic bone marrow (BM) samples
      of 13 MDS patients. HOXA9 was expressed by CD34(+) BM cells at median levels 3.1
      fold higher than in CD34(-) cells from the same patient and at median levels 4.3
      fold higher than in CD34(+) cells from healthy donors. These results indicate
      that CD34(+) cell selection is required to accurately assess the expression
      levels of HOXA9 and related genes in the multipotential malignant progenitor
      cells of MDS patients.

PMID- 15982347
TI  - Osteosclerosis in advanced chronic idiopathic myelofibrosis is associated with
      endothelial overexpression of osteoprotegerin.
AB  - Advanced chronic idiopathic myelofibrosis (IMF) with osteosclerosis and increase
      and thickening of bone trabeculae is typically contrasted by the absence or
      sparse presence of osteoclasts. Because osteoclast formation can be inhibited by
      osteoprotegerin (OPG) we investigated OPG expression in IMF with severe fibrosis
      and osteosclerosis, which expressed significantly higher (up to 71-fold) OPG mRNA
      levels when compared with prefibrotic cellular IMF and control cases. The
      receptor activator of nuclear factor kappaB ligand (RANKL), a positive regulator
      of osteoclast differentiation and putative antagonist of OPG was overexpressed by
      up to 34-fold exclusively in advanced IMF. Case-specific calculation of the
      RANKL/OPG ratio in advanced IMF showed a wide range without significant
      differences when compared with the prefibrotic IMF and non-neoplastic
      haematopoiesis. Immunohistochemical detection of OPG protein revealed strong
      labelling of endothelial cells within proliferating vessels in fibrotic IMF and
      heterogeneously labelled megakaryocytes, and fibroblasts. Osteosclerosis and
      impaired osteoclast function in IMF appears to be associated with upregulated
      endothelial OPG expression but concomitant reduction of the antagonist RANKL
      could not be demonstrated. We conclude that osteosclerosis in IMF is associated
      with increased endothelial OPG expression without concomitant RANKL
      downregulation.

PMID- 15982349
TI  - Severe and prolonged myeloid haematopoietic toxicity with myelodysplastic
      features following alemtuzumab therapy in patients with peripheral T-cell
      lymphoproliferative disorders.
AB  - Alemtuzumab is effective therapy for B- and T-cell lymphoproliferative disorders
      (LPD) but is associated with prolonged lymphopenia. Myeloid haematological
      toxicities are less well described, especially in T-cell disorders, and are
      usually transient. We report myeloid toxicities in a phase II trial of
      alemtuzumab for T-cell LPD. Five of 11 patients treated developed severe
      neutropenia and thrombocytopenia. Three cases had prolonged cytopenias (32-88+
      weeks), including two with severe marrow hypoplasia. We observed three incidences
      of trilineage morphological myelodysplasia, two with new clonal cytogenetic
      abnormalities. Alemtuzumab can be associated with prolonged severe multilineage
      cytopenias, marrow hypoplasia and myelodysplasia in T-cell LPD.

PMID- 15982350
TI  - Vaccination of patients with haematological malignancies with one or two doses of
      influenza vaccine: a randomised study.
AB  - An open, randomised study was performed to determine whether two doses of
      influenza vaccine were more effective than one to elicit an immune response in 70
      patients with haematological malignancies. The responses were not improved by two
      doses compared with one (influenza A virus serotypes H1/N1 18% vs. 22% and H3/N2
      26% vs. 14%; influenza B 25% vs. 22%). The results were similar in patients with
      ongoing and discontinued therapy. Patients treated with monoclonal antibodies for
      lymphoma had very poor responses. We conclude that two doses of influenza vaccine
      do not improve the antibody response in patients with haematological
      malignancies.

PMID- 15982351
TI  - Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation
      from HLA-matched related donors in patients with Fanconi anaemia.
AB  - Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for
      Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of
      cyclophosphamide (Cy), typically used in aplastic anaemia. We previously
      published results of studies in which Cy doses were gradually reduced from 200 to
      100 mg/kg. Here we update results of the initial studies and report data on 30
      new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n =
      23), given over 4 days before HCT from human leucocyte antigen-matched related
      donors. Methotrexate and cyclosporine were given for graft-versus-host disease
      (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy
      at 60 mg/kg had sustained engraftment, while two patients, both with clonal
      cytogenetics abnormalities, experienced graft failure. Grades 2-3 acute GVHD
      rates were 57% and 14% for patients given the higher and lower Cy doses,
      respectively (P = 0.001). Four patients given Cy at 80 mg/kg and 22 given Cy at
      60 mg/kg were alive at a median of 47 (44-58) months and 16 (3-52) months,
      respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is
      sufficient for engraftment of related grafts in most FA patients.

PMID- 15982352
TI  - Can long-term prophylaxis for severe haemophilia be stopped in adulthood? Results
      from Denmark and the Netherlands.
AB  - Prophylaxis is the treatment of choice for children with severe haemophilia. As
      prophylaxis is especially important during the period of growth, the need for
      continued prophylaxis in adulthood should be considered. The aim of this study
      was to describe the incidence and outcome of stopping prophylaxis in patients
      with severe haemophilia who were offered prophylaxis during childhood. All
      patients with severe haemophilia (factor VIII/IX <0.01 IU/ml), born 1970-80,
      treated in two Danish and one Dutch treatment centre were studied. Data on
      discontinuation of prophylaxis, treatment, joint bleed frequency, clinical scores
      and radiological scores were collected. Eighty patients were studied. Median
      follow-up was 19 years (range 7-29). A total of 35% of patients discontinued
      prophylaxis at a median age of 21.5 years [interquartile range (IQR) 18.4-24.4],
      experiencing only three joint bleeds per year (IQR 1.4-8.7). Median clinical
      scores were similar in patients who discontinued prophylaxis [4 points (IQR 0-6)]
      and those who continued [3 points (IQR 1-6)], as were median Pettersson scores at
      13 (IQR 1-24) vs. 13 points (IQR 5-23) respectively. In conclusion one-third of
      young adults with severe haemophilia on a prophylactic regimen discontinued
      prophylaxis in early adulthood, while maintaining a low joint bleed frequency and
      similar arthropathy after 4 years.

PMID- 15982353
TI  - Impaired bradykinin response to ischaemia and exercise in patients with mild
      congestive heart failure during angiotensin-converting enzyme treatment.
      Relationships with endothelial function, coagulation and inflammation.
AB  - Inflammation and endothelial dysfunction play important roles in the
      pathophysiology of congestive heart failure (CHF), and the peptide bradykinin,
      generated during inflammation, may act as a defence mechanism by inducing
      vasodilation. Plasma bradykinin levels are increased in experimental heart
      failure but low in patients with advanced chronic CHF despite treatment with
      angiotensin-converting enzyme (ACE) inhibitors. It is not currently known how
      bradykinin behaves in less severe phases of CHF controlled by long-term ACE
      inhibitor treatment. We studied 10 male patients with clinically stable chronic
      CHF [New York Heart Association (NYHA) class II] on long-term ACE inhibitor
      treatment and 10 normal sex- and age-matched control subjects. High performance
      liquid chromatography/radioimmunoassay methods were used to evaluate plasma
      levels of bradykinin in relation to an array of parameters of endothelial
      function, coagulation and inflammation before and after stimuli of forearm
      arterial occlusion and physical exercise. CHF patients had higher levels of
      bradykinin (P = 0.008), activated factor XII (P = 0.049), interleukin-6 (P =
      0.050) and tumour necrosis factor receptor II (sTNFRII) (P = 0.026) than
      controls. Arterial occlusion and exercise significantly increased bradykinin and
      von Willebrand factor levels in controls but not in CHF patients. The increase in
      brachial artery diameter after arterial occlusion was less in CHF patients (P =
      0.036) and inversely related to baseline plasma levels of bradykinin (r = -0.855,
      P = 0.002) and sTNFRII (r = -0.780, P = 0.008). NYHA class II CHF patients during
      long-term treatment with ACE inhibitors have increased bradykinin levels and
      signs of inflammation. They are unable to respond adequately to stimuli of
      ischaemia and physical exercise which both require vasodilation.

PMID- 15982354
TI  - Co-operative signalling mechanisms required for erythroid precursor expansion in
      response to erythropoietin and stem cell factor.
AB  - The regeneration of circulating red blood cells in response to anaemia associated
      with blood loss or haemolysis involves an increased rate of erythropoiesis and
      expansion of proerythroblasts, the bone marrow precursor cells that terminally
      differentiate into mature erythrocytes. This study investigated the mechanisms by
      which erythropoietin (Epo) and stem cell factor (Scf) modulate the expansion of
      proerythroblasts. Homogenous populations of primary human proerythroblasts were
      generated in liquid cultures of CD34(+) cells. In serum-free cultures,
      proerythroblasts failed to survive in the presence of Epo or Scf alone, but
      exhibited synergistic proliferation in response to combined Epo and Scf
      treatment, exhibiting one-log expansion in 5 d. Intracellular signal transduction
      in response to Epo and Scf revealed that tyrosine phosphorylation of signal
      transducers and activators of transcription (Stat) 5, a downstream target for the
      non-receptor tyrosine kinase, Janus kinase 2 (Jak2), was mediated by Epo but not
      Scf. The mitogen-activated protein kinases (MAPKs) extracellular regulated kinase
      (Erk) 1-2 were phosphorylated in response to either Epo or Scf. Phosphorylation
      of Akt, a signalling molecule downstream of phosphatidylinositol 3-kinase (PI3K),
      was observed following Scf but not Epo treatment. To determine the contribution
      of specific signalling pathways to synergistic expansion of proerythroblasts in
      response to co-operative effects of Epo and Scf, cells were treated with kinase
      inhibitors targeting Jak2, PI3K and MAPK kinase. There was a significant, dose
      dependent inhibition of proerythroblast expansion in response to all three kinase
      inhibitors. In conclusion, Epo- and Scf-mediated co-operative, synergistic
      expansion of primary erythroid precursors requires selective activation of
      multiple signalling pathways, including the Jak-Stat, PI3K and MAPK pathways.

PMID- 15982355
TI  - A novel human CD32 mAb blocks experimental immune haemolytic anaemia in
      FcgammaRIIA transgenic mice.
AB  - A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc
      gamma receptor IIa (FcgammaRIIa) molecules on CD32 transfectants, peripheral
      blood monocytes, polymorphonuclear cells and platelets. This antibody blocked
      FcgammaRIIa ligand-binding via its F(ab')(2) fragment. Overnight incubation of
      monocytes with F(ab')(2) fragments of MDE-8 leads to a c. 60% decrease in cell
      surface expression of FcgammaRIIa. MDE-8 whole antibody induced a concomitant c.
      30% decrease of FcgammaRI on THP-1 cells and monocytes. In humans FcgammaRIIa
      plays an important role in the clearance of antibody-coated red blood cells in
      vivo. As an equivalent of FcgammaRIIa does not exist in mice, the in vivo effect
      of MDE-8 was studied in an FcgammaRIIa transgenic mouse model. In these mice,
      antibody-induced anaemia could readily be blocked by MDE-8. These data document a
      new human antibody that effectively blocks FcgammaRIIa, induces modulation of
      both FcgammaRIIa and FcgammaRI from phagocytic cells, and ameliorates antibody
      induced anaemia in vivo.

PMID- 15982356
TI  - The measurement of urinary hydroxyurea in sickle cell anaemia.
AB  - Hydroxyurea is increasingly used in the treatment of sickle cell disease (SCD)
      although there is little evidence on how best to monitor treatment and
      compliance. It is also not known why 10-50% patients do not benefit from the drug
      and whether some of this resistance is because of pharmacokinetic factors. We
      have developed an assay using mass spectrometry (MS) to measure urinary
      concentrations of hydroxyurea. We have used this assay to study 12 children and
      six adults with SCD taking hydroxyurea and found that urinary hydroxyurea was
      present for at least 12 h following tablet ingestion. Thirty-five urine samples
      were analysed that were expected to contain hydroxyurea, based on the reported
      timing of the last dose and hydroxyurea was detected in 29 (83%) of these. There
      were also marked differences in urinary hydroxyurea concentrations, suggesting
      pharmacokinetic variability may explain some of the differences in response to
      hydroxyurea. Urine samples were also analysed by MS for penicillin metabolites
      and 43 of the 57 (75%) contained phenoxyacetate, suggesting the ingestion of
      penicillin within the last 12 h. These assays are potentially useful to study
      hydroxyurea metabolism further, develop optimal dosing regimes and monitor
      compliance with treatment.

PMID- 15982357
TI  - Efficacy and inhibitor development in previously treated patients with
      haemophilia A switched to a B domain-deleted recombinant factor VIII -
      clarification of Kogenate inhibitor data.

PMID- 15982359
TI  - The NF-kappaB pathway and the successful application of anti-inflammatory and
      angiostatic therapy in Langerhans' cell histiocytosis.

PMID- 15982360
TI  - Factors predicting development of chronic disease in Nordic children with acute
      onset of idiopathic thrombocytopenic purpura.

PMID- 15982362
TI  - Stand up for evolution.

PMID- 15982363
TI  - Diversification of nubbin expression patterns in arthropods: data from an
      additional spider species, Cupiennius salei.

PMID- 15982364
TI  - Echinoderm rudiments, rudimentary bilaterians, and the origin of the chordate
      CNS.

PMID- 15982365
TI  - Cytokines in the oviparity/viviparity transition: evidence of the interleukin-1
      system in a species with reproductive bimodality, the lizard Lacerta vivipara.
AB  - Placental viviparity is a reproductive strategy usually attributed to mammals.
      However, it is also present in other vertebrate species, e.g. in Squamate
      reptiles. Although the immunological mechanisms that allow the survival of the
      semi-allogenic embryo in maternal tissues are still largely unknown, cytokines
      seem to play an important role in mammalian reproduction. Previous studies in our
      laboratory showed that interleukin-1 (IL-1), a cytokine associated with
      implantation in mice, is also expressed at the materno-fetal interface of
      placental viviparous Squamates. In this study, we used the model of Lacerta
      vivipara, which exhibits reproductive bimodality, that is, the coexistence of
      oviparous and viviparous populations. By means of immunohistochemistry and anti
      human antibodies, we showed that uterine tissues of L. vivipara (seven oviparous
      and six viviparous animals) expressed the two IL-1 isoforms, IL-1alpha and IL
      1beta, and the type I IL-1 receptor (IL-1R tI) both at the pre-ovulatory stage
      and during gestation, with no significant difference between oviparous and
      viviparous females. In L. vivipara, as in most oviparous Squamates, an important
      phase of embryonic development takes place in the mother's oviduct, before egg
      laying. Moreover, although thinner than in oviparous females, an eggshell
      membrane persists throughout gestation in viviparous females also, which develop
      a very simple type of placenta. The data suggest that immunological mechanisms
      that allow the survival of the semi-allogenic embryo in maternal tissues are
      independent of the timing or intimacy of contact between maternal and fetal
      tissues.

PMID- 15982366
TI  - Co-option of an oral-aboral patterning mechanism to control left-right
      differentiation: the direct-developing sea urchin Heliocidaris erythrogramma is
      sinistralized, not ventralized, by NiCl2.
AB  - Larval dorsoventral (DV) and left-right (LR) axial patterning unfold
      progressively in sea urchin development, leading to commitment of the major
      embryonic regions by the gastrula stage. The direct-developing sea urchin
      Heliocidaris erythrogramma has lost oral-aboral differentiation along the DV axis
      but has accelerated vestibular ectoderm development on the left side. NiCl(2)
      radializes indirect-developing sea urchins by shifting cells toward a ventral
      fate (oral ectoderm). We treated embryos of H. erythrogramma and the indirect
      developing H. tuberculata with NiCl(2). H. tuberculata was ventralized exactly
      like other indirect developers, establishing that basic patterning mechanisms are
      conserved in this genus. H. erythrogramma was also radialized; timing, dosage
      response, and some morphological features were similar to those in other sea
      urchins. Ectodermal explant and recombination experiments demonstrate that the
      effect of nickel is autonomous to the ectoderm, another feature in common with
      indirect developers. However, H. erythrogramma is distinctly sinistralized rather
      than ventralized, its cells shifting toward a left-side fate (vestibular
      ectoderm). This geometric contrast in the midst of pervasive functional
      similarity suggests that nickel-sensitive processes in H. erythrogramma axial
      patterning, homologous to those in indirect developers, have been redeployed, and
      hence co-opted, from their ancestral role in DV axis determination to a new role
      in LR axis determination. We discuss DV and LR axial patterning and their
      evolutionary transformation.

PMID- 15982367
TI  - Evolutionary redeployment of a biosynthetic module: expression of eye pigment
      genes vermilion, cinnabar, and white in butterfly wing development.
AB  - Ommochromes are common among insects as visual pigments; however, in some insect
      lineages ommochromes have evolved novel functions such as integument coloration
      and tryptophan secretion. One role of ommochromes, as butterfly wing pigments,
      can apparently be traced to a single origin in the family Nymphalidae. The
      synthesis and storage of ommochrome pigments is a complex process that requires
      the concerted activity of multiple enzyme and transporter molecules. To help
      understand how this subcellular process appeared in a novel context during
      evolution, we explored aspects of ommochrome pigment development in the wings of
      the nymphalid butterfly Vanessa cardui. Using chromatography and radiolabeled
      precursor incorporation studies we identified the ommochrome xanthommatin as a V.
      cardui wing pigment. We cloned fragments of two ommochrome enzyme genes,
      vermilion and cinnabar, and an ommochrome precursor transporter gene, white, and
      found that these genes were transcribed in wing tissue at relatively high levels
      during wing scale development. Unexpectedly, however, the spatial patterns of
      transcription were not associated in a simple way with adult pigment patterns.
      Although our results suggest that the evolution of ommochrome synthesis in
      butterfly wings likely arose in part through novel regulation of vermilion,
      cinnabar, and white transcription, they also point to a complex relationship
      between transcriptional prepatterns and pigment synthesis in V. cardui.

PMID- 15982368
TI  - Growth patterns during segmentation in the two polychaete annelids, Capitella sp.
      I and Hydroides elegans: comparisons at distinct life history stages.
AB  - Many animals generate new body segments sequentially from a posterior growth
      zone, and this is generally thought to be the case for the annelids. Most
      annelids, including polychaetes, have an indirect life cycle and generate their
      earliest segments during larval life. We have characterized the nature of the
      growth zone in two polychaetes, Hydroides elegans and Capitella sp. I, during
      both larval and juvenile stages of segment formation by examining cell division
      patterns with 5-bromo-2'-deoxyuridine incorporation. Cell division patterns show
      commonalities between the two species, even though they have distinct body plans
      and life history characteristics. In both polychaetes, larval segments arise from
      a field of dividing cells located in lateral regions of the body, rather than
      from a localized posterior growth zone. Circumferential expansion of the forming
      segmental tissue is particularly pronounced in Capitella sp. I. Post-metamorphic
      segments, in contrast, originate from a classical posterior growth zone, with the
      exception of four posterior thoracic segments of H. elegans, which appear to
      arise from an area in the middle of the body, indicating plasticity of segment
      generating mechanisms present in different annelid life histories. The distinct
      nature of larval versus juvenile growth zones in H. elegans and Capitella sp. I
      raises the question of the mechanistic relationship between these two growth
      zones. The results of this study increase our understanding of the cellular
      origins of segments in annelids, and serve as a basis for interpretation of
      molecular expression patterns associated with segment formation in polychaetes.

PMID- 15982369
TI  - The inter-specific hybrid Silene latifolia x S. viscosa reveals early events of
      sex chromosome evolution.
AB  - The dioecious plant species Silene latifolia has a sex determination mechanism
      based on an active Y chromosome. Here, we used inter-specific hybrids in the
      genus Silene to study the effects of gene complexes on the Y chromosome. If the
      function of Y-linked genes has been maintained in the same state as in the
      hermaphrodite progenitor species, it should be possible to substitute such genes
      by genes coming from a related hermaphrodite species. In the inter-specific
      hybrid, S. latifolia x S. viscosa, anthers indeed develop far beyond the early
      bilobal stage characteristic of XX S. latifolia female plants. The S. viscosa
      genome can thus replace the key sex determination gene whose absence abolishes
      early stamen development in females (loss of the stamen-promoting function, SPF),
      so that hybrid plants are morphologically hermaphrodite. However, the hybrids
      have two anther development defects, loss of adhesion of the tapetum to the
      endothecium, and precocious endothecium maturation. Both these defects were also
      found in independent Y-chromosome deletion mutants of S. latifolia. The data
      support the hypothesis that the evolution of complete gender dimorphism from
      hermaphroditism involved a major largely recessive male-sterility factor that
      created females, and the appearance of new, dominant genes on the Y chromosome,
      including both the well-documented gynoecium-suppressing factor, and two other Y
      specific genes promoting anther development.

PMID- 15982370
TI  - Molting polychaete jaws--ecdysozoans are not the only molting animals.
AB  - Jaw shedding and replacement of Diopatra aciculata (Onuphidae, Eunicida), by the
      same process as arthropod molting, involving apolysis and ecdysis, is described
      here. These observations suggest that molting has either evolved convergently in
      eunicidan polychaetes and ecdysozoans or it was present in the last
      ecdysozoan/lophotrochozoan common ancestor and thus may not represent a
      synapomorphy of the ecdysozoans.

PMID- 15982371
TI  - Environmental signaling and evolutionary change: can exposure of pregnant mammals
      to environmental estrogens lead to epigenetically induced evolutionary changes in
      embryos?
AB  - DNA methylation is one of the epigenetic and hereditary mechanisms regulating
      genetic expression in mammalian cells. In this review, we propose how certain
      natural agents, through their dietary consumption, could induce changes in
      physiological aspects in mammalian mothers, leading to alterations in DNA
      methylation patterns of the developing fetus and to the emergence of new
      phenotypes and evolutionary change. Nevertheless, we hypothesize that this
      process would require (i) certain key periods in the ontogeny of the organism
      where the environmental stimuli could produce effects, (ii) particular
      environmental agents as such stimuli, and (iii) that a genomic persistent change
      be consequently produced in a population. Depending on the persistence of the
      environmental stimuli and on whether the affected genes are imprinted genes,
      induced changes in DNA methylation patterns could become persistent. Moreover,
      some fragments could be more frequently methylated than others over several
      generations, leading to biased base change and evolutionary consequences.

PMID- 15982372
TI  - The origin of the endothelial cells: an evo-devo approach for the
      invertebrate/vertebrate transition of the circulatory system.
AB  - Circulatory systems of vertebrate and invertebrate metazoans are very different.
      Large vessels of invertebrates are constituted of spaces and lacunae located
      between the basement membranes of endodermal and mesodermal epithelia, and they
      lack an endothelial lining. Myoepithelial differentation of the coelomic cells
      covering hemal spaces is a frequent event, and myoepithelial cells often form
      microvessels in some large invertebrates. There is no phylogenetic theory about
      the origin of the endothelial cells in vertebrates. We herein propose that
      endothelial cells originated from a type of specialized blood cells, called
      amoebocytes, that adhere to the vascular basement membrane. The transition
      between amoebocytes and endothelium involved the acquisition of an epithelial
      phenotype. We suggest that immunological cooperation was the earliest function of
      these protoendothelial cells. Furthermore, their ability to transiently recover
      the migratory, invasive phenotype of amoebocytes (i.e., the angiogenic phenotype)
      allowed for vascular growth from the original visceral areas to the well
      developed somatic areas of vertebrates (especially the tail, head, and neural
      tube). We also hypothesize that pericytes and smooth muscle cells derived from
      myoepithelial cells detached from the coelomic lining. As the origin of blood
      cells in invertebrates is probably coelomic, our hypothesis relates the origin of
      all the elements of the circulatory system with the coelomic wall. We have
      collected from the literature a number of comparative and developmental data
      supporting our hypothesis, for example the localization of the vascular
      endothelial growth factor receptor-2 ortholog in hemocytes of Drosophila or the
      fact that circulating progenitors can differentiate into endothelial cells even
      in adult vertebrates.

PMID- 15982374
TI  - The effect of insomnia definitions, terminology, and classifications on clinical
      practice.
AB  - There is a need for newer, more clinically useful classifications for insomnia.
      Identification of specific subtypes of insomnia helps anchor research, allows for
      prediction of prognosis/course of the condition, and may allow for
      individualization of treatment. Existing classifications differ, and many terms
      remain inadequately defined, which leads to diagnostic confusion. Historically,
      insomnia has been classified according to symptom type, symptom duration, and
      underlying cause, but these classifications have not been based on evidence of
      their utility, and newer research suggests the need for change. Symptoms may
      include difficulty falling asleep, trouble staying asleep, and not feeling
      restored by sleep, although it has not been clear that it is possible to identify
      distinct subtypes of patients by symptom or that distinguishing symptom type
      affects the course of clinical treatment. Classification of insomnia by duration
      most commonly involves three categories: transient (no more than a few days),
      short-term (up to 3 weeks), and long-term (more than 3 weeks). This
      categorization is of uncertain utility and has been primarily based on nonempiric
      concerns about treatment with sedative-hypnotic medications for periods longer
      than several weeks. The subtyping of insomnia in terms of whether there is an
      identifiable underlying cause such as a psychiatric or medical illness was based
      on an unproven assumption that in most instances other disorders caused insomnia.
      Recent studies suggest the need to revisit these classification strategies.
      Evidence that symptom types typically overlap and change over time complicates
      the categorization of subjects by whether they have difficulty falling asleep or
      staying asleep or have nonrestorative sleep. New studies of the treatment of
      chronic insomnia change the perspective on duration of treatment and, as a
      result, classification of duration of disease. Two studies of nightly
      pharmacotherapy for insomnia including more than 800 insomnia patients have not
      identified any increase in the risks after 3 to 4 weeks of treatment. In
      addition, nonpharmacological treatments demonstrate long-lasting efficacy in
      patients with chronic insomnia, and the development of abbreviated cognitive
      behavioral therapies, which are particularly well suited to primary care
      practice, have improved their applicability. Newer studies of the relationships
      between insomnia and associated medical and psychiatric conditions undermine the
      notion that insomnia is always a symptom and caused by an underlying condition.
      They suggest that, although it is important to identify and treat these
      conditions, this may not be sufficient to alleviate the insomnia, which may
      adversely affect the course of the associated disorder. As a result, treatment
      targeted specifically to the insomnia should be considered. All of these
      developments point to an increasing ability to tailor therapy to the particular
      needs of patients and to optimize the clinical management of insomnia.

PMID- 15982375
TI  - Prevalence and comorbidity of insomnia and effect on functioning in elderly
      populations.
AB  - A good night's sleep is often more elusive as we age, because the prevalence of
      insomnia in older people is high. Insufficient sleep can have important effects
      on daytime function by increasing the need to nap, reducing cognitive ability
      including attention and memory, slowing response time, adversely affecting
      relationships with friends and family, and contributing to a general sense of
      being unwell. However, rather than aging per se, circadian rhythm shifts, primary
      sleep disorders, comorbid medical/psychiatric illnesses, and medication use cause
      sleep difficulties in older people, which psychosocial factors may also affect.
      Clinicians should ask elderly patients about satisfaction with sleep. Any sleep
      complaints warrant careful evaluation of contributing factors and appropriate
      treatment.

PMID- 15982376
TI  - Diagnosis and management of insomnia in older people.
AB  - Insomnia is a common but underrecognized problem in elderly patients. Five basic
      steps can help clinicians identify and treat insomnia. The first step is to ask a
      single question about sleep at every new patient visit, which goes a long way
      toward detection of patients with insomnia. The second step is to perform an
      initial evaluation of the problem, including symptoms, contributing factors, and
      effects on daytime function. Step three is to determine whether the patient is in
      crisis. True sleep emergencies are rare, and in most cases, treatment can be
      delayed until another appointment can be made for a full evaluation of the
      problem. A sleep evaluation constitutes the fourth step and focuses mainly on a
      thorough sleep history; blood tests and polysomnography rarely have a role. The
      final step is intervention. Nonpharmacological strategies are a mainstay of
      treatment for chronic insomnia, but hypnotics have a role in treating transient
      insomnia and chronic insomnia that does not improve with nonpharmacological
      treatment or treatment of associated primary conditions. Pharmacological therapy
      usually consists of benzodiazepines with short half-lives or nonbenzodiazepines
      such as zolpidem and zaleplon, although lack of demonstrated efficacy against
      sleep maintenance difficulties, one of the primary symptoms of insomnia among
      older people, limits use of these agents. Emerging nonbenzodiazepine agents such
      as indiplon and eszopiclone may specifically address sleep maintenance problems
      in elderly patients and are pending Food and Drug Administration (FDA) approval.
      (Editor's note: Since preparation of this manuscript, the FDA has approved
      eszopiclone for treatment of insomnia.).

PMID- 15982379
TI  - Profile and competences for the European dentist.
AB  - This paper presents the profile and competences for the European Dentist as
      approved by the General Assembly of the Association for Dental Education in
      Europe at its annual meeting held in Cardiff in September 2004. A task-force
      drafted the document, which was then sent to all European Dental Schools.
      Reactions received were used to amend the document. European dental schools are
      expected to adhere to the profile and the 17 major competences but the supporting
      competences may vary in detail between schools. The document will be reviewed in
      5 years time. This paper will be disseminated to ministries of health, national
      dental associations and dental specialty associations or societies in Europe and
      these organisations will be asked to offer their comments. This information will
      be used in the reviewing process to be started in 2007. It is hoped that the
      availability of this document will assist dental schools in Europe to further
      harmonize and improve the quality of their curricula.

PMID- 15982380
TI  - Self-reported changes in clinical behaviour by undergraduate dental students
      after video-based teaching in paediatric dentistry.
AB  - Four cohorts of undergraduate students (n = 113) were filmed on video tapes
      whilst performing paediatric treatments. Selected parts of these tapes were shown
      the day after. Thus, within one term each student was able to view his
      performance on a videotape as well as those of fellow students. After completion
      of the clinical course in paediatric dentistry students were asked by means of a
      questionnaire about behavioural changes in their clinical work regarding
      different topics. Considerable changes in behaviour were reported for various
      topics. Most of the students emphasised the viable role of the video for changing
      their behaviour. This was especially true for aspects of verbal and non-verbal
      communication where mainly female students benefited. Moreover, video was thought
      to have been useful for improving capacities to deal with patients in fear or
      pain and for ergonomics. About two-thirds of the students (64.6%) thought that
      watching the video had made it easier for them to put theoretical knowledge into
      action. Video does not seem to play an important role for confirmation and
      maintenance of behaviour patterns. In conclusion however, it can be stated that
      video has a high impact on the modification of behaviour patterns of
      undergraduate students for many aspects of clinical work. The use of video can
      thus attribute to dental education in an effective way.

PMID- 15982381
TI  - Perceptions of admission committee members: some aspects on individual admission
      to dental education at Karolinska Institutet.
AB  - The aim of the study was to generate an overall impression of the admission
      committee's (AC) perspective on individualised admission procedures, derived from
      some perceived experience of the individual committee members using semi
      structured interviews. Qualitative research was used and data were collected by
      use of interviews. The results show that the committee members are highly
      committed to the task and try to identify desirable, non-cognitive attributes in
      the applicants, such as motivation, empathy, drive, and tenacity: 'emotional
      intelligence'. The committee members were of the opinion that it was possible to
      identify these attributes in an applicant. The AC further believes that the
      admissions procedure influences academic achievements because students regard
      themselves as specially selected and therefore aspire to higher achievements.

PMID- 15982382
TI  - German dental faculty attitudes towards computer-assisted learning and their
      correlation with personal and professional profiles.
AB  - BACKGROUND: Compared with its potential, computer technology use is still lacking
      in medical/dental education. OBJECTIVES: To investigate the primary advantages of
      computer-assisted learning (CAL) systems in German dental education, as well as
      the reasons for their relatively low degree of use correlated with personal and
      professional profiles of respondents. METHOD: A questionnaire was mailed to heads
      in the departments of conservative dentistry and prosthetic dentistry in all
      dental schools in Germany. Besides investigating the advantages and barriers to
      the use of computer technology, the questionnaire also contained questions
      regarding each respondent's gender, age, academic rank, experience in academia
      and computer skills. RESULTS: The response rate to the questionnaire was 90% (112
      of 125). The results indicated a distinct discrepancy between the desire for and
      actual occurrence of lectures, seminars, etc. to instruct students in ways to
      search for and acquire knowledge, especially using computer technology. The
      highest-ranked advantages of CAL systems in order, as seen by respondents, were
      the possibilities for individual learning, increased motivation, and both
      objective theoretical tests and practical tests. The highest-ranked reasons for
      the low degree of usage of CAL systems in order were the inability to finance,
      followed equally by a lack of studies of CAL and poor cost-advantage ratio, and
      too much effort required to integrate CAL into the curriculum. Moreover, the
      higher the computer skills of the respondents, the more they noted insufficient
      quality of CAL systems (r = 0.200, P = 0.035) and content differences from their
      own dental faculty's expert opinions (r = 0.228, P = 0.016) as reasons for low
      use. CONCLUSION: The correlations of the attitudes towards CAL with the personal
      and professional profiles showed not only statistical significant reinforcements
      of, but also interesting deviations from, the average responses.

PMID- 15982383
TI  - Teaching and learning in dental student clinical practice.
AB  - Clinical learning in restorative dentistry is principally centred around the
      provision of patient care, yet we know very little about the learning processes
      occurring within the clinical environment. A study of undergraduate dental
      student clinical practice used a combination of group interview and questionnaire
      techniques to explore some of the characteristics of student/teacher interaction
      that students finds significant, and which they consider to affect their learning
      of clinical skills. Study data, when analysed, revealed three major categories of
      teacher or student behaviour which appear to be of importance to students. This
      paper focuses on one of these, describing a number of behaviours, grouped
      together under the category of 'teaching/learning behaviours'. The aim of the
      paper is to report these results and to discuss their application to clinical
      teaching of restorative dentistry.

PMID- 15982384
TI  - The Anglo-Italian collaboration: a report of the first steps in implementing the
      Bologna Declaration.
AB  - This report summarises the accomplishments of King's College London and
      Universita degli Studi di Brescia in establishing an Anglo-Italian Collaboration.
      The aim was to develop areas of enterprise in clinical practice, teaching and
      research that reflected the principles of the Bologna Declaration.

PMID- 15982385
TI  - ADEE report.

PMID- 15982386
TI  - Re: "acceptance of sentinel lymph node biopsy of the breast by all general
      surgeons in kentucky," by Conn et al.

PMID- 15982387
TI  - Acceptance of sentinel lymph node biopsy of the breast by all general surgeons in
      kentucky.
AB  - Sentinel lymph node biopsy (SLNB) for breast cancer is now performed routinely in
      many U.S. medical centers. The acceptance of SLNB in the community and in rural
      medical centers, however, has not been accurately defined. The purpose of this
      study was to assess how surgeons in Kentucky, a predominantly rural state, have
      incorporated SLNB into practice. General surgeons in the state of Kentucky were
      identified by registration with the state medical association. All general
      surgeons (n=272) in the state were mailed the questionnaire, with 93% (n=252)
      responding. Overall, 172 defined themselves as rural surgeons. Among the rural
      surgeons, 87% perform breast cancer operations and 54% perform SLNB. In
      comparison, 74% of nonrural surgeons perform breast cancer operations and 80%
      perform SLNB. A majority of nonrural surgeons (73%) have performed SLNB for more
      than 2 years when compared to rural surgeons (73% versus 37%, respectively;
      p<0.0001). Planned backup axillary node dissection was stopped by both rural
      (26%) and community (39%) surgeons after 10 cases (14% rural, 19% nonrural) or 11
      -20 cases (12% rural, 20% nonrural). Surgeons reported using SLNB for the
      following diagnoses: invasive cancer (98%), ductal carcinoma in situ (DCIS)
      (43%), and lobular carcinoma in situ (LCIS) (11%). The majority of surgeons (87%)
      reported a greater than 90% SLN identification rate. SLNB has become widely
      accepted by surgeons in both rural and nonrural medical centers in Kentucky.
      However, there has been considerable variability in the number of training cases
      surgeons have performed prior to abandoning routine axillary dissection. This
      indicates a need for continuing educational efforts aimed at quality assurance.

PMID- 15982388
TI  - Physiologic changes in breast magnetic resonance imaging during the menstrual
      cycle: perfusion imaging, signal enhancement, and influence of the T1 relaxation
      time of breast tissue.
AB  - This study was undertaken to determine the best time during the menstrual cycle
      to perform dynamic breast magnetic resonance imaging (MRI). The contralateral
      "normal" breast of 50 premenopausal women (mean age 40.4 +/- 6.4 years, range 30-
      52 years) were enrolled in a protocol designed to correlate an ipsilateral
      suspicious breast lesion with pathology. The contralateral breast in each patient
      was examined with palpation and mammography prior to MRI on a 1.5 T scanner using
      gradient echo and dynamic contrast-enhanced echo-planar without and following
      gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) injection. Pre-contrast
      T1 relaxation times were measured before calculating extraction flow product
      (EFP) maps using a multicompartmental model. T1, EFP, and enhancement were
      measured in the control breast on four slices centered around the nipple and
      recorded as a function of the phases of the menstrual cycle. Lesions or areas
      with focal enhancement were excluded. Analysis of variance and Fisher's tests
      were performed. The cyclic changes in T1 relaxation time were not significant
      (p>0.2). EFP and enhancement varied significantly during the cycle (p<0.003 and
      p<0.004, respectively), with low values during the first half of the cycle and
      high values during the second half. The lowest values of EFP and enhancement
      (5.5+/-2.9 ml/100 g/min and 26+/-17%) were observed during the proliferative
      phase (days 3--7), and the highest values (17+/-10.2 ml/100 g/min and 104+/-28%)
      were observed during the secretory phase (days 21-27) (p<0.0006 and p<0.0008,
      respectively). Dynamic breast MRI should be performed during first half of the
      menstrual cycle (days 3--14) in order to minimize interpretative difficulties
      related to the uptake of gadolinium in normal breast tissue due to hormonal
      fluctuations during the menstrual cycle.

PMID- 15982389
TI  - Defining negative margins in DCIS patients treated with breast conservation
      therapy: The University of Chicago experience.
AB  - Management of ductal carcinoma in situ (DCIS) has been evolving and the majority
      of women are now being treated with breast-conserving surgery and radiation
      therapy (i.e. breast conservation therapy [BCT]). Controversies still exist
      regarding the histologic features and margin status that are associated with
      local recurrence. The goal of this study was to review our institution's
      experience in patients diagnosed with DCIS and treated with BCT to determine
      pathologic features that can predict local recurrence, with particular emphasis
      on the final surgical margin status. We analyzed 103 consecutive patients with
      DCIS who were treated with BCT between 1986 and 2000. The slides were reviewed to
      determine the final margin status, type of DCIS, size of DCIS, nuclear grade,
      presence of necrosis and calcification, and volume of excised specimen. Margins
      were considered positive when DCIS touched or was transected at an inked margin.
      Negative margins were further categorized as close (less than 1 mm), 1--5 mm, and
      more than 5 mm. The size of the DCIS was determined based on either the maximal
      dimension on a slide or from the number of consecutive slides containing DCIS.
      Morphology and immunohistochemical profiles of the recurrent DCIS cases were
      compared with original DCIS. All patients were treated uniformly with external
      beam radiation therapy to the entire breast (median dose 46 Gy) with a boost to
      the tumor bed (median dose 14 Gy). The median follow-up was 63 months (range 7-
      191 months). The actuarial 5-year local control rate was 89%. The median time to
      local recurrence was 55 months. There were 13 local recurrences, of which 9
      recurred as pure DCIS and 4 as invasive ductal carcinomas. Univariate analysis
      showed a significant association with local recurrence for positive margin
      (p=0.008), high nuclear grade (p=0.02), and young age at diagnosis (p=0.03). If
      margins were negative, the 5-year local control was 93%, as compared to 69% if
      margins were positive. A multivariate analysis showed that early age at
      diagnosis, positive margin status, and high nuclear grade were independently
      associated with local recurrence. The morphology and immunohistochemical stains
      of all nine recurrent DCIS were similar to those of the original DCIS. Breast
      conservation can be achieved with excellent local control by obtaining
      microscopically negative margins as strictly defined by DCIS not touching the
      inked surgical margins, and postoperative radiation that includes boost therapy
      to the tumor bed.

PMID- 15982390
TI  - Ratio of positive to total number of sentinel nodes predicts nonsentinel node
      status in breast cancer patients.
AB  - Selective sentinel lymphadenectomy (SSL) has replaced axillary lymph node
      dissection (ALND) for many patients with early breast cancer and negative
      sentinel lymph nodes (SLNs). Yet many patients with a positive SLN are undergoing
      unnecessary ALND, as no further disease is found in the axilla. The aim of our
      study was to determine factors associated with additional positive lymph nodes in
      the axilla in patients who have a positive SLN. This was a retrospective study of
      patients undergoing SSL with ALND as part of their treatment for breast cancer at
      a single institution from November 1997 to August 2003. Only patients with one or
      more positive SLNs were selected for this study. There were 86 patients who fit
      our study criteria. Of these, 38% had further positive lymph nodes upon ALND.
      More than one positive SLN and a ratio of positive SLNs to total SLNs of greater
      than 0.5 were found to be predictors for additional axillary nodal involvement in
      both univariate and multivariate analyses. The number of positive SLNs and the
      ratio of positive SLNs to total SLNs is an indication of total tumor burden in
      the sentinel nodes and may be a reflection of the propensity of the tumor for
      further lymphatic invasion in the axillary basin.

PMID- 15982391
TI  - How mammillary fistulas should be managed.
AB  - Mammillary fistulas are uncommon, but when they occur they cause prolonged
      morbidity. The etiology and management strategies are less well established. The
      purpose of this study is to evaluate the etiologic factors and assess the results
      of surgical treatment. It is a retrospective study of all patients treated for
      mammillary fistula from 1990 to 2001. The clinical data, including complications
      of surgical treatment, were collected from medical records. Fistulas were
      segregated into simple and complex fistulas before analyzing the results of
      surgical treatment. Thirty-five patients were treated during this period. A
      history of either drainage of a subareolar abscess or spontaneous rupture of an
      inflammatory mass preceded the development of mammillary fistula in the majority
      of patients. Previous Hadfield's procedure for duct ectasia contributed to the
      development of fistula in seven patients. Seventeen patients presented with
      simple fistula. A large proportion of them were treated by total duct excision in
      recent years, with a higher rate of recurrence (4/6). Eighteen patients presented
      with complex fistulas; two of them had recurrences following surgical treatment.
      The overall recurrence rate was 23%. The majority of the patients showed features
      of periductal mastitis on histologic examination. Postoperative wound infection
      was positively associated with fistula recurrence. The best management of
      mammillary fistula remains a problem. Simple fistulas should be treated by
      fistulectomy and primary closure. Total duct excision should be reserved for
      complex fistulas. Postoperative wound infection is also a major factor in fistula
      recurrence. All patients should receive antibiotics. Surgery for duct ectasia has
      caused fistulas in 20% of cases in our study, raising the issue of restricting
      total duct excision to more severe forms of the disease. Mammillary fistulas
      should be treated more appropriately in a specialized breast unit with particular
      interest in benign breast disease.

PMID- 15982392
TI  - Breast implants as a possible etiology of epithelioid hemangioendothelioma and
      successful therapy with interferon-alpha2.
AB  - Epithelioid hemangioendothelioma is a rare vascular tumor with unpredictable
      behavior. It often presents as liver or lung nodules and is refractory to
      conventional chemotherapy. Surgical resection and/or liver transplantation have
      been the mainstay of therapy, but the results are mixed and unsatisfactory.
      Although the etiology of this malignancy is unknown, an increased incidence in
      women has been noted, and an association with exposure to vinyl chloride is
      emerging as a possible risk factor. This review proposes polyurethane/silicone
      breast implants as a potential cause of the condition and highlights the dramatic
      response to interferon (IFN)-alpha in a woman, so exposed, with widespread
      disease in the liver and lungs. The implications for other women who have had
      this type of implant could be significant, and the early use of IFN-alpha may be
      optimal.

PMID- 15982393
TI  - Risk factors for duct ectasia.
AB  - Duct ectasia consists of dilation of the mammary ducts and is clinically
      manifested as nipple discharge, which is more commonly multiductal, bilateral,
      and colored. To identify clinical factors that might be related to duct ectasia.
      A case-control study was carried out on a population of 150 patients divided into
      two groups. Group 1 (the experimental group) comprised 100 patients with
      multiductal, bilateral, and colored nipple discharge, clinically representing the
      nipple secretion of duct ectasia. Group 2 (the control group) was composed of 50
      patients without nipple discharge. The odds ratio of duct ectasia was three times
      higher for current smokers (p=0.04). Likewise, smokers from the duct ectasia
      group had smoked for a longer time (median 25 months) compared to smokers from
      the control group (median 15 months) (p=0.02). Parity, history of abortion or
      termination, breast-feeding, hormonal contraceptive use, and history of breast
      abscess did not increase the risk for duct ectasia. The group of women with duct
      ectasia was associated with current tobacco smoking.

PMID- 15982394
TI  - A case-control study evaluating the association of purposeful physical activity,
      body fat distribution, and steroid hormones on premenopausal breast cancer risk.
AB  - The objective of this case-control study was to investigate the relationship
      between purposeful physical activity, body fat distribution, body mass index, and
      steroid hormones. These factors are known to be implicated in modulating breast
      cancer risk in premenopausal women. A total of 112 newly diagnosed, premenopausal
      breast cancer patients and 106 age-matched premenopausal disease-free controls
      were admitted to the study. Information regarding personal, medical, hormonal,
      and reproductive history, smoking and alcohol use, physical activity history, and
      anthropometric measurements was obtained. Serum samples for steroid hormone
      assays were collected and analyzed. Disease-free premenopausal controls had a
      significantly higher physical activity index (PAI) (p</=0.05), however,
      significantly higher weight (p</=0.05), body mass index (BMI) (p=0.01), waist
      (p</=0.005) and hip (p</=0.05) circumferences, waist:hip ratios (p</=0.05), and
      serum total estradiol levels (p<0.0005) were observed in cancer cases. The final
      model using stepwise logistic regression analysis indicates that the variables
      that significantly predicted breast cancer risk were waist:hip ratio (odds ratio
      [OR]=1.11, p</=0.005) and serum total estradiol levels (OR=1.03, p</=0.0001). Our
      study provides some evidence that purposeful physical activity may reduce upper
      body fat distribution associated with adult weight gain. This may be a result of
      alterations in the steroid hormone pathway, such as reduced estradiol levels.
      This demonstrates the potential mechanism through which increased physical
      activity can reduce the risk for breast cancer in premenopausal women.

PMID- 15982395
TI  - Full-thickness chest wall resection for recurrence of breast malignancy.
AB  - We present outcomes in 13 consecutive patients with solitary, local chest wall
      recurrence subsequent to mastectomy for breast malignancy who were operated on in
      1983--2001. All patients underwent full-thickness chest wall resection (FTCWR)
      and immediate reconstruction. The mean chest wall defect area was 108 cm(2). The
      choice of reconstruction method was individualized. The reconstruction was
      accomplished with the patient's own tissues, in three cases supported by
      artificial mesh. Most commonly we used the contralateral breast or myocutaneous
      flap. We did not observe postoperative complications. The tissues used for the
      reconstruction provided sufficient stiffness of the rib cage. In all specimens
      the surgical margins were negative. The estimated 5-year survival after excision
      of recurrent tumor is 62%. FTCWR with immediate reconstruction with soft tissues
      should be considered in patients with local solitary recurrence after mastectomy
      for breast malignancy. This option offers good long-term results and minimal
      morbidity.

PMID- 15982396
TI  - Correlation of her-2/neu gene amplification with other prognostic and predictive
      factors in female breast carcinoma.
AB  - The purpose of this study was to determine if any relationship exists between Her
      2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR),
      MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen
      female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in
      which assessment of Her-2/neu amplification by fluorescence in-situ hybridization
      (FISH) has been performed, were reviewed retrospectively. Each patient was
      further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square
      analysis was then used to correlate the above observations. Overall gene
      amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%)
      were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive
      cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22
      (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases.
      Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified
      in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of
      49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198
      grade III tumors. Lobular carcinomas were not graded. Amplification was present
      in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%)
      out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified
      in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women
      40 years and younger. Comparison of these frequencies using chi-square test
      revealed statistically significant correlation between Her-2/neu amplification
      and ductal versus lobular carcinoma (p<0.0003), ER (p=0.0001) and PR (p<0.0001)
      negative tumors, over-expression of MIB-1 (p<0.0005) and high tumor grade
      (p=0.0009), while size of the tumor (p=0.08) and age of the patients (p=0.67)
      were not statistically significant. Correlation was found between Her-2/neu
      amplification and tumor type, high histological grade, ER and PR negative tumors,
      and high proliferative MIB-1 index. No correlation was found between size of the
      tumor and age of the patient with Her-2/neu amplification.

PMID- 15982397
TI  - Adult Langerhans cell histiocytosis mimicking Paget's disease of the nipple.

PMID- 15982398
TI  - Lupus mastitis.

PMID- 15982399
TI  - Phyllodes tumor with pseudoangiomatous stroma hyperplasia.

PMID- 15982400
TI  - Glycogen-rich "clear cell" carcinoma of the breast.

PMID- 15982401
TI  - Mastitis granulomatosis.

PMID- 15982402
TI  - Collagen plug metallic marker clip: mammographic and histopathologic appearance.

PMID- 15982403
TI  - Fibromatosis of the male breast.

PMID- 15982404
TI  - Pseudotumor of the breast: an unusual presentation of Wegener's granulomatosis.

PMID- 15982405
TI  - Extramammary recurrence of DCIS after total mastectomy: an iatrogenic
      displacement following needling procedures?

PMID- 15982406
TI  - Breast cancer-related pseudocirrhosis and esophageal varices.

PMID- 15982407
TI  - The 3rd International Symposium on the Molecular Biology of Breast Cancer. Molde,
      Norway, 22-26 June 2005. Abstracts.

PMID- 15982409
TI  - A road map of yeast interactions.

PMID- 15982408
TI  - Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae
      interaction network.
AB  - BACKGROUND: Large-scale studies have revealed networks of various biological
      interaction types, such as protein-protein interaction, genetic interaction,
      transcriptional regulation, sequence homology, and expression correlation.
      Recurring patterns of interconnection, or 'network motifs', have revealed
      biological insights for networks containing either one or two types of
      interaction. RESULTS: To study more complex relationships involving multiple
      biological interaction types, we assembled an integrated Saccharomyces cerevisiae
      network in which nodes represent genes (or their protein products) and
      differently colored links represent the aforementioned five biological
      interaction types. We examined three- and four-node interconnection patterns
      containing multiple interaction types and found many enriched multi-color network
      motifs. Furthermore, we showed that most of the motifs form 'network themes' --
      classes of higher-order recurring interconnection patterns that encompass
      multiple occurrences of network motifs. Network themes can be tied to specific
      biological phenomena and may represent more fundamental network design
      principles. Examples of network themes include a pair of protein complexes with
      many inter-complex genetic interactions -- the 'compensatory complexes' theme.
      Thematic maps -- networks rendered in terms of such themes -- can simplify an
      otherwise confusing tangle of biological relationships. We show this by mapping
      the S. cerevisiae network in terms of two specific network themes. CONCLUSION:
      Significantly enriched motifs in an integrated S. cerevisiae interaction network
      are often signatures of network themes, higher-order network structures that
      correspond to biological phenomena. Representing networks in terms of network
      themes provides a useful simplification of complex biological relationships.

PMID- 15982410
TI  - Untangling the web of functional and physical interactions in yeast.
AB  - An analysis of an integrated network of over 150,000 functional and physical
      interactions in yeast suggests that the network can be hierarchically decomposed
      into themes and thematic maps. This decomposition can be used to explore the
      organizational principles of integrated biological networks within cells.

PMID- 15982411
TI  - Expansion of antibody reactivity in the cerebrospinal fluid of multiple sclerosis
      patients - follow-up and clinical implications.
AB  - BACKGROUND: An intrathecal polyspecific antibody response is a well known finding
      in multiple sclerosis. However, little is known about the evolution of
      intrathecal antibodies over time and their impact on the disease progress.
      Therefore, we focused in this study on the intrathecal polyspecific antibody
      response in multiple sclerosis. METHODS: Here we present a follow-up study of 70
      patients with multiple sclerosis over 1 to 106 months. Serum and cerebrospinal
      fluid sample pairs were obtained from 1 to 5 consecutive lumbar punctures. CSF
      cell count, the IgG index, local IgG synthesis, oligoclonal bands and the
      antibody index for measles, rubella or varicella zoster were calculated. Results
      were analysed with regard to clinical characteristics of the patients. RESULTS:
      Once an intrathecal antibody response was established, it persisted. De novo
      antibody response against measles virus developed in 7% of the patients between
      the first and the second spinal tap. In two of seven patients where 5 consecutive
      CSF samples were available, the intrathecal antibody response expanded from one
      to three antigens. Furthermore, an intrathecal measles antibody production was
      associated with a rapid progression of the disease. CONCLUSION: These data stress
      the importance of activated B cells for the disease process and the clinical
      outcome in multiple sclerosis.

PMID- 15982412
TI  - Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G
      mutation have dysmorphic nuclei and are hypersensitive to heat stress.
AB  - BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare
      sporadic disorder with an incidence of approximately 1 per 8 million live births.
      The phenotypic appearance consists of short stature, sculptured nose, alopecia,
      prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial
      cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene
      that encodes nuclear lamins A and C. The most common mutation in subjects with
      HGPS is a de novo single-base pair substitution, G608G (GGC>GGT), within exon 11
      of LMNA. This creates an abnormal splice donor site, leading to expression of a
      truncated protein. RESULTS: We studied a new case of a 5 year-old girl with HGPS
      and found a heterozygous point mutation, G608G, in LMNA. Complementary DNA
      sequencing of RNA showed that this mutation resulted in the deletion of 50 amino
      acids in the carboxyl-terminal tail domain of prelamin A. We characterized a
      primary dermal fibroblast cell line derived from the subject's skin. These cells
      expressed the mutant protein and exhibited a normal growth rate at early passage
      in primary culture but showed alterations in nuclear morphology. Expression
      levels and overall distributions of nuclear lamins and emerin, an integral
      protein of the inner nuclear membrane, were not dramatically altered.
      Ultrastructural analysis of the nuclear envelope using electron microscopy showed
      that chromatin is in close association to the nuclear lamina, even in areas with
      abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat
      shock, and demonstrated a delayed response to heat stress. CONCLUSION: Dermal
      fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have
      dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat
      stress. This suggests that the mutant protein, even when expressed at low levels,
      causes defective cell stability, which may be responsible for phenotypic
      abnormalities in the disease.

PMID- 15982413
TI  - Executive and motivational processes in adolescents with Attention-Deficit
      Hyperactivity Disorder (ADHD).
AB  - BACKGROUND: The objective of the current study was to examine performance and
      correlates of performance on a decision-making card task involving risky choices
      (Iowa Gambling Task) in adolescents with ADHD and comparison controls. Forty-four
      participants with ADHD and 34 controls were administered measures of estimated
      intellectual ability, working memory, and the card task. Also, behavioural
      ratings were obtained from parents and teachers. RESULTS: Adolescents with ADHD
      scored lower on the measures of intellectual ability, working memory, and made
      less advantageous selections on the card task compared to controls. Performance
      on measures of intellectual ability and working memory were unrelated to card
      task performance in both the ADHD and control samples. Parent ratings of
      hyperactivity/impulsivity were significantly associated with card task
      performance in the adolescents with ADHD, but not in controls. CONCLUSION: These
      findings demonstrate impaired decision-making in adolescents with ADHD, and the
      separability of motivational and executive function processes, supporting current
      dual pathway models of ADHD.

PMID- 15982414
TI  - "Anxiebo", placebo, and postoperative pain.
AB  - BACKGROUND: Surgical treatment and its consequences expose patients to stress,
      and here we investigated the importance of the psychological component of
      postoperative pain based on reports in the clinical literature. DISCUSSION:
      Postoperative pain remains a significant clinical problem. Increased pain
      intensity with increased demand for opioid medication, and/or a relative
      unresponsiveness to pain treatment was reported both when the analgesia was
      administered by means of conventional nurse injection regimes and patient
      controlled analgesia (PCA). Both the quality of the analgesia, and the
      sensitivity of postoperative models for assessing analgesic efficacy could be
      significantly influenced. The findings could be explained by increased
      penetration of an algesic anxiety-related nocebo influence (which we chose to
      call "anxiebo") relative to its analgesic placebo counterpart. To counteract this
      influence, the importance of psychological effects must be acknowledged, and
      doctors and attending nurses should focus on maintaining trustful therapist
      patient relationships throughout the treatment period. The physical mechanism of
      anxiebo should be further explored, and those at risk for anxiebo better
      characterized. In addition, future systemic analgesic therapies should be
      directed towards being prophylactic and continuous to eliminate surgical pain as
      it appears in order to prevent the anxiebo effect. Addressing anxiebo is the key
      to developing reproducible models for measuring pain in the postoperative
      setting, and to improving the accuracy of measurements of the minimum effective
      analgesic concentration. SUMMARY: Anxiebo and placebo act as counterparts
      postoperatively. The anxiebo state may impair clinical analgesia and reduce the
      sensitivity of analgesic trials. Ways to minimize anxiebo are discussed.

PMID- 15982415
TI  - PMD2HD--a web tool aligning a PubMed search results page with the local German
      Cancer Research Centre library collection.
AB  - BACKGROUND: Web-based searching is the accepted contemporary mode of retrieving
      relevant literature, and retrieving as many full text articles as possible is a
      typical prerequisite for research success. In most cases only a proportion of
      references will be directly accessible as digital reprints through displayed
      links. A large number of references, however, have to be verified in library
      catalogues and, depending on their availability, are accessible as print holdings
      or by interlibrary loan request. METHODS: The problem of verifying local print
      holdings from an initial retrieval set of citations can be solved using Z39.50,
      an ANSI protocol for interactively querying library information systems. Numerous
      systems include Z39.50 interfaces and therefore can process Z39.50 interactive
      requests. However, the programmed query interaction command structure is non
      intuitive and inaccessible to the average biomedical researcher. For the typical
      user, it is necessary to implement the protocol within a tool that hides and
      handles Z39.50 syntax, presenting a comfortable user interface. RESULTS: PMD2HD
      is a web tool implementing Z39.50 to provide an appropriately functional and
      usable interface to integrate into the typical workflow that follows an initial
      PubMed literature search, providing users with an immediate asset to assist in
      the most tedious step in literature retrieval, checking for subscription holdings
      against a local online catalogue. CONCLUSION: PMD2HD can facilitate literature
      access considerably with respect to the time and cost of manual comparisons of
      search results with local catalogue holdings. The example presented in this
      article is related to the library system and collections of the German Cancer
      Research Centre. However, the PMD2HD software architecture and use of common
      Z39.50 protocol commands allow for transfer to a broad range of scientific
      libraries using Z39.50-compatible library information systems.

PMID- 15982416
TI  - WWOX protein expression varies among ovarian carcinoma histotypes and correlates
      with less favorable outcome.
AB  - BACKGROUND: The putative tumor suppressor WWOX gene spans the common chromosomal
      fragile site 16D (FRA16D) at chromosome area 16q23.3-24.1. This region is a
      frequent target for loss of heterozygosity and chromosomal rearrangement in
      ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias. The
      goal of these studies was to evaluate WWOX protein expression levels in ovarian
      carcinomas to determine if they correlated with clinico-pathological parameters,
      thus providing additional support for WWOX functioning as a tumor suppressor.
      METHODS: We performed WWOX protein expression analyses by means of immunobloting
      and immunohistochemistry on normal ovaries and specific human ovarian carcinoma
      Tissue Microarrays (n = 444). Univariate analysis of clinical-pathological
      parameters based on WWOX staining was determined by chi2 test with Yates'
      correction. The basic significance level was fixed at p < 0.05. RESULTS:
      Immunoblotting analysis from normal ovarian samples demonstrated consistently
      strong WWOX expression while 37% ovarian carcinomas showed reduced or
      undetectable WWOX protein expression levels. The immunohistochemistry of normal
      human ovarian tissue sections confirmed strong WWOX expression in ovarian surface
      epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444
      ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely
      detectable WWOX expression. The remaining ovarian carcinomas (70%) stained
      moderately to strongly positive for this protein. The two histotypes showing
      significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell
      (42%) types. Reduced WWOX expression demonstrated a significant association with
      clinical Stage IV (FIGO) (p = 0.007), negative Progesterone Receptor (PR) status
      (p = 0.008) and shorter overall survival (p = 0.03). CONCLUSION: These data
      indicate that WWOX protein expression is highly variable among ovarian carcinoma
      histotypes. It was also observed that subsets of ovarian tumors demonstrated loss
      of WWOX expression and is potentially associated with patient outcome.

PMID- 15982417
TI  - Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical
      cancer. Predictive and prognostic significance.
AB  - BACKGROUND: It has been shown that free DNA circulates in serum plasma of
      patients with cancer and that at least part is present in the form of oligo- and
      monucleosomes, a marker of cell death. Preliminary data has shown a good
      correlation between decrease of nucleosomes with response and prognosis. Here, we
      performed pre- and post-chemotherapy determinations of serum nucleosomes with an
      enzyme-linked immunosorbent assay (ELISA) method in a group of patients with
      cervical cancer receiving neoadjuvant chemotherapy. METHODS: From December 2000
      to June 2001, 41 patients with cervical cancer staged as FIGO stages IB2-IIIB
      received three 21-day courses of carboplatin and paclitaxel, both administered at
      day 1; then, patients underwent radical hysterectomy. Nucleosomes were measured
      the day before (baseline), at day seven of the first course and day seven of the
      third course of chemotherapy. Values of nucleosomes were analyzed with regard to
      pathologic response and to time to progression-free and overall survival.
      RESULTS: All patients completed chemotherapy, were evaluable for pathologic
      response, and had nucleosome levels determined. At a mean follow-up of 23 months
      (range, 7-26 months), projected progression time and overall survival were 80.3
      and 80.4%, respectively. Mean differential values of nucleosomes were lower in
      the third course as compared with the first course (p >0.001). The decrease in
      the third course correlated with pathologic response (p = 0.041). Survival
      analysis showed a statistically significant, better progression-free and survival
      time in patients who showed lower levels at the third course (p = 0.0243 and p =
      0.0260, respectively). Cox regression analysis demonstrated that nucleosome
      increase in the third course increased risk of death to 6.86 (95% confidence
      interval [CI 95%], 0.84-56.0). CONCLUSION: Serum nucleosomes may have a
      predictive role for response and prognostic significance in patients with
      cervical cancer patients treated with neoadjuvant chemotherapy.

PMID- 15982418
TI  - Isolated rural general practice as the focus for teaching core clinical rotations
      to pre-registration medical students.
AB  - BACKGROUND: Earlier studies have successfully demonstrated that medical students
      can achieve success in core clinical rotations with long term attachments in
      small groups to rural general / family practices. METHODS: In this study, three
      students from a class of 226 volunteered for this 1-year pilot program, conducted
      by the University of Queensland in 2004, for medical students in the 3rd year of
      a 4-year graduate entry medical course. Each student was based with a private
      solo general practitioner in a different rural town between 170 and 270 km from
      the nearest teaching hospital. Each was in a relatively isolated rural setting,
      rated 5 or 6 on the RRMA scale (Rural, Remote, Metropolitan Classification:
      capital city = 1, other metropolitan = 2, large regional city = 3, most remote
      community = 7). The rural towns had populations respectively of 500, 2000 and
      10,000. One practice also had a General Practice registrar. Only one of the
      locations had doctors in the same town but outside the teaching practice, while
      all had other doctors within the same area. All 3 supervisors had hospital
      admitting rights to a hospital within their town. The core clinical rotations of
      medicine, surgery, mental health, general practice and rural health were
      primarily conducted within these rural communities, with the student based in
      their own consulting room at the general practitioner (GP) supervisor's surgery.
      The primary teacher was the GP supervisor, with additional learning opportunities
      provided by visiting specialists, teleconferences and university websites. At
      times, especially during medicine and surgery terms, each student would return to
      the teaching hospital for additional learning opportunities. RESULTS: All
      students successfully completed the year. There were no statistical differences
      in marks at summative assessment in each of the five core rotations between the
      students in this pilot and their peers at the metropolitan or rural hospital
      based clinical schools. CONCLUSION: The results suggest that isolated rural
      general practice could provide a more substantial role in medical student
      education.

PMID- 15982419
TI  - Differential gene expression profile reveals deregulation of pregnancy specific
      beta1 glycoprotein 9 early during colorectal carcinogenesis.
AB  - BACKGROUND: APC (Adenomatous polyposis coli) plays an important role in the
      pathogenesis of both familial and sporadic colorectal cancer. Patients carrying
      germline APC mutations develop multiple colonic adenomas at younger age and
      higher frequency than non-carrier cases which indicates that silencing of one APC
      allele may be sufficient to initiate the transformation process. METHODS: To
      elucidate the biological dysregulation underlying adenoma formation we examined
      global gene expression profiles of adenomas and corresponding normal mucosa from
      an FAP patient. Differential expression of the most significant gene identified
      in this study was further validated by mRNA in situ hybridization, reverse
      transcriptase PCR and Northern blotting in different sets of adenomas, tumours
      and cancer cell lines. RESULTS: Eighty four genes were differentially expressed
      between all adenomas and corresponding normal mucosa, while only seven genes
      showed differential expression within the adenomas. The first group included
      pregnancy specific beta-1 glycoprotein 9 (PSG9) (p < 0.006). PSG9 is a member of
      the carcinoembryonic antigen (CEA)/PSG family and is produced at high levels
      during pregnancy, mainly by syncytiotrophoblasts. Further analysis of sporadic
      and familial colorectal cancer confirmed that PSG9 is ectopically upregulated in
      vivo by cancer cells. In total, deregulation of PSG9 mRNA was detected in 78%
      (14/18) of FAP adenomas and 75% (45/60) of sporadic colorectal cancer cases
      tested. CONCLUSION: Detection of PSG9 expression in adenomas, and at higher
      levels in FAP cases, indicates that germline APC mutations and defects in Wnt
      signalling modulate PSG9 expression. Since PSG9 is not found in the non-pregnant
      adult except in association with cancer, and it appears to be an early molecular
      event associated with colorectal cancer monitoring of its expression may be
      useful as a biomarker for the early detection of this disease.

PMID- 15982420
TI  - Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young
      adults. I. Antibody concentrations, avidity and functional activity.
AB  - Streptococcus pneumoniae is a serious worldwide pathogen and the focus of
      numerous vaccine development projects. Currently the most widely accepted
      surrogate marker for evaluating the efficacy of a given vaccine is to utilize
      ELISA. Measurement of antibody concentration by ELISA without reduction in cross
      reactive antibodies causes an overestimation of antibody concentration and
      therefore protection, this is most notable in the aged, an at risk group for this
      infection. We compared the immune response to the pneumococcal polysaccharides
      (PPS) 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG
      antibody concentrations and antibody avidity against PPS4 and PPS14 were measured
      using two different enzyme-linked immunosorbant assay (ELISA) absorption
      protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS),
      or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody
      concentrations for serotype 4, but not 14, were significantly lowered with the
      additional absorption with serotype 22F polysaccharide in both age groups. Young
      and elderly demonstrated a significant increase from pre- to post-immunization
      antibody concentration, using either absorption method; and opsonophagocytic
      antibody titers in response to both PPS4 and PPS14. The correlation coefficients
      between ELISA and opsonophagocytic assays were improved by additional absorption
      with serotype 22F in response to serotype 4, but not serotype 14 in all age
      groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of
      age) were significantly lower than the opsonophagocytic antibody concentrations
      in young adults. These results suggest the importance of eliminating cross
      reactive antibodies from ELISA measurements by absorption of serum and an age
      related impairment in the antibody response to pneumococcal polysaccharides.

PMID- 15982421
TI  - A cluster randomized trial to assess the impact of opinion leader endorsed
      evidence summaries on improving quality of prescribing for patients with chronic
      cardiovascular disease: rationale and design [ISRCTN26365328].
AB  - BACKGROUND: Although much has been written about the influence of local opinion
      leaders on clinical practice, there have been few controlled studies of their
      effect, and almost none have attempted to change prescribing in the community for
      chronic conditions such as heart failure (HF) or ischemic heart disease (IHD).
      These two conditions are common and there is very good evidence about how to best
      prevent morbidity and mortality - and good evidence that quality of care is, in
      general, suboptimal. Practice audits have demonstrated that about one-half of
      eligible HF patients are prescribed ACE inhibitors (with fewer still reaching
      appropriate target doses) and less than one-third of patients with established
      IHD are prescribed statins (with many fewer reaching recommended cholesterol
      targets). It is apparent that interventions to improve quality of prescribing are
      urgently needed. We hypothesized that an intervention that consisted of patient
      specific one-page evidence summaries, generated and then endorsed by local
      opinion leaders, would be able to change prescribing practices of community-based
      primary care physicians. METHODS (STUDY DESIGN): A pragmatic single-centre
      cluster randomized controlled trial comparing an opinion leader-based
      intervention to usual care for patients with HF or IHD. Randomization will be
      clustered at the level of the primary care physician; as the design effect is
      anticipated to be negligible, the unit of analysis will be the patient. Patients
      with HF or IHD (not receiving ACE inhibitors or statins, respectively) will be
      recruited from community pharmacies and allocated to intervention or usual care
      based on the randomization status of their primary care physician. The primary
      outcome is improvement in prescription of proven efficacious therapies for HF
      (ACE inhibitors) or IHD (statins) within 6 months of the intervention.
      CONCLUSION: If the methods used in this intervention are found to improve
      prescribing practices, similar interventions could be designed for other chronic
      conditions dealt with in the outpatient setting.

PMID- 15982422
TI  - Modeling Lactococcus lactis using a genome-scale flux model.
AB  - BACKGROUND: Genome-scale flux models are useful tools to represent and analyze
      microbial metabolism. In this work we reconstructed the metabolic network of the
      lactic acid bacteria Lactococcus lactis and developed a genome-scale flux model
      able to simulate and analyze network capabilities and whole-cell function under
      aerobic and anaerobic continuous cultures. Flux balance analysis (FBA) and
      minimization of metabolic adjustment (MOMA) were used as modeling frameworks.
      RESULTS: The metabolic network was reconstructed using the annotated genome
      sequence from L. lactis ssp. lactis IL1403 together with physiological and
      biochemical information. The established network comprised a total of 621
      reactions and 509 metabolites, representing the overall metabolism of L. lactis.
      Experimental data reported in the literature was used to fit the model to
      phenotypic observations. Regulatory constraints had to be included to simulate
      certain metabolic features, such as the shift from homo to heterolactic
      fermentation. A minimal medium for in silico growth was identified, indicating
      the requirement of four amino acids in addition to a sugar. Remarkably, de novo
      biosynthesis of four other amino acids was observed even when all amino acids
      were supplied, which is in good agreement with experimental observations.
      Additionally, enhanced metabolic engineering strategies for improved diacetyl
      producing strains were designed. CONCLUSION: The L. lactis metabolic network can
      now be used for a better understanding of lactococcal metabolic capabilities and
      potential, for the design of enhanced metabolic engineering strategies and for
      integration with other types of 'omic' data, to assist in finding new information
      on cellular organization and function.

PMID- 15982423
TI  - The influence of hydrogen peroxide and histamine on lung permeability and
      translocation of iridium nanoparticles in the isolated perfused rat lung.
AB  - BACKGROUND: Translocation of ultrafine particles (UFP) into the blood that
      returns from the lungs to the heart has been forwarded as a mechanism for
      particle-induced cardiovascular effects. The objective of this study was to
      evaluate the role of the endothelial barrier in the translocation of inhaled UFP
      from the lung into circulation. METHODS: The isolated perfused rat lung (IPRL)
      was used under negative pressure ventilation, and radioactive iridium particles
      (18 nm, CMD, 192Ir-UFP) were inhaled during 60 minutes to achieve a lung burden
      of 100-200 microg. Particle inhalation was done under following treatments: i)
      control perfusion, ii) histamine (1 microM) in perfusate, iii) luminal histamine
      instillation (1 mM), and iv) luminal instillation of H2O2. Particle translocation
      to the perfusate was assessed by the radioactivity of 192Ir isotope. Lung
      permeability by the use of Tc99m-labeled diethylene triamine pentaacetic acid
      (DTPA). In addition to light microscopic morphological evaluation of fixed lungs,
      alkaline phosphatase (AKP) and angiotensin converting enzyme (ACE) in perfusate
      were measured to assess epithelial and endothelial integrity. RESULTS: Particle
      distribution in the lung was homogenous and similar to in vivo conditions. No
      translocation of Ir particles at negative pressure inhalation was detected in
      control IPL, but lungs pretreated with histamine (1 microM) in the perfusate or
      with luminal H2O2 (0.5 mM) showed small amounts of radioactivity (2-3 % dose) in
      the single pass perfusate starting at 60 min of perfusion. Although the kinetics
      of particle translocation were different from permeability for 99mTc-DTPA, the
      pretreatments (H2O2, vascular histamine) caused similar changes in the
      translocation of particles and soluble mediator. Increased translocation through
      epithelium and endothelium with a lag time of one hour occurred in the absence of
      epithelial and endothelial damage. CONCLUSION: Permeability of the lung barrier
      to UFP or nanoparticles is controlled both at the epithelial and endothelial
      level. Conditions that affect this barrier function such as inflammation may
      affect translocation of NP.

PMID- 15982424
TI  - Depression and Obstructive Sleep Apnea (OSA).
AB  - For over two decades clinical studies have been conducted which suggest the
      existence of a relationship between depression and Obstructive Sleep Apnea (OSA).
      Recently, Ohayon underscored the evidence for a link between these two disorders
      in the general population, showing that 800 out of 100,000 individuals had both,
      a breathing-related sleep disorder and a major depressive disorder, with up to
      20% of the subjects presenting with one of these disorders also having the other.
      In some populations, depending on age, gender and other demographic and health
      characteristics, the prevalence of both disorders may be even higher: OSA may
      affect more than 50% of individuals over the age of 65, and significant
      depressive symptoms may be present in as many as 26% of a community-dwelling
      population of older adults. In clinical practice, the presence of depressive
      symptomatology is often considered in patients with OSA, and may be accounted for
      and followed-up when considering treatment approaches and response to treatment.
      On the other hand, sleep problems and specifically OSA are rarely assessed on a
      regular basis in patients with a depressive disorder. However, OSA might not only
      be associated with a depressive syndrome, but its presence may also be
      responsible for failure to respond to appropriate pharmacological treatment.
      Furthermore, an undiagnosed OSA might be exacerbated by adjunct treatments to
      antidepressant medications, such as benzodiazepines. Increased awareness of the
      relationship between depression and OSA might significantly improve diagnostic
      accuracy as well as treatment outcome for both disorders. In this review, we will
      summarize important findings in the current literature regarding the association
      between depression and OSA, and the possible mechanisms by which both disorders
      interact. Implications for clinical practice will be discussed.

PMID- 15982425
TI  - Personal customizing exercise with a wearable measurement and control unit.
AB  - BACKGROUND: Recently, wearable technology has been used in various health-related
      fields to develop advanced monitoring solutions. However, the monitoring function
      alone cannot meet all the requirements of customizing machine-based exercise on
      an individual basis by relying on biosignal-based controls. We propose a new
      wearable unit design equipped with measurement and control functions to support
      the customization process. METHODS: The wearable unit can measure the heart rate
      and electromyogram signals during exercise performance and output workload
      control commands to the exercise machines. The workload is continuously tracked
      with exercise programs set according to personally customized workload patterns
      and estimation results from the measured biosignals by a fuzzy control method.
      Exercise programs are adapted by relying on a computer workstation, which
      communicates with the wearable unit via wireless connections. A prototype of the
      wearable unit was tested together with an Internet-based cycle ergometer system
      to demonstrate that it is possible to customize exercise on an individual basis.
      RESULTS: We tested the wearable unit in nine people to assess its suitability to
      control cycle ergometer exercise. The results confirmed that the unit could
      successfully control the ergometer workload and continuously support gradual
      changes in physical activities. CONCLUSION: The design of wearable units equipped
      with measurement and control functions is an important step towards establishing
      a convenient and continuously supported wellness environment.

PMID- 15982426
TI  - Hyperventilation in severe diabetic ketoacidosis.
AB  - OBJECTIVE: To explore whether the carbon dioxide-bicarbonate (P(CO(2))-HCO(3))
      buffering system in blood and cerebrospinal fluid (CSF) in diabetic ketoacidosis
      should influence the approach to ventilation in patients at risk of cerebral
      edema. DATA SOURCE: Medline search, manual search of references in articles found
      in Medline search, and use of historical literature from 1933 to 1967. DESIGN: A
      clinical vignette is used--a child with severe diabetic ketoacidosis who
      presented with profound hypocapnia and then deteriorated--as a basis for
      discussion of integrative metabolic and vascular physiology. STUDY SELECTION:
      Studies included reports in diabetic ketoacidosis where arterial and CSF acid
      base data have been presented. Studies where simultaneous acid-base, ventilation,
      respiratory quotient, and cerebral blood flow data are available. DATA EXTRACTION
      AND SYNTHESIS: We revisit a hypothesis and, by reassessing data, put forward an
      argument based on the significance of low [HCO(3)](CSF) and rising Pa(CO(2))-
      hyperventilation in diabetic ketoacidosis and the limit in biology of survival;
      repair of severe diabetic ketoacidosis and Pa(CO(2))-and mechanical ventilation.
      CONCLUSION: The review highlights a potential problem with mechanical ventilation
      in severe diabetic ketoacidosis and suggests that the P(CO(2))--HCO(3) hypothesis
      is consistent with data on cerebral edema in diabetic ketoacidosis. It also
      indicates that the recommendation to avoid induced hyperventilation early in the
      course of intensive care may be counter to the logic of adaptive physiology.

PMID- 15982427
TI  - Aggressive management of dengue shock syndrome may decrease mortality rate: a
      suggested protocol.
AB  - OBJECTIVES: Dengue shock syndrome is a leading cause of mortality among Indian
      children. In January 2000, we instituted a protocol for aggressive management of
      children with dengue shock syndrome. The objective of this study was to compare
      outcomes (duration of ventilation, pediatric intensive care unit stay, incidence
      of acute respiratory distress syndrome, and intensive care unit and hospital
      mortality) before and after the protocol. DESIGN: Retrospective chart review.
      SETTING: Pediatric intensive care unit at a tertiary teaching hospital. PATIENTS:
      One hundred and fourteen patients admitted between July 1997 and December 1999
      received standard therapy recommended by the World Health Organization (WHO) and
      were designated as the WHO guidelines group (W), whereas 96 patients admitted
      between January 2000 and December 2001 were treated by our protocol and
      designated as the protocol group (P). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The patients in each group were equally matched in terms of age,
      Pediatric Risk of Mortality, and number with dengue hemorrhage fever grade IV,
      although the platelet counts were higher in the W group compared with the P group
      (geometric mean 42.2, confidence interval 36.9, 48.4 vs. geometric mean 36.7,
      confidence interval 33.3, 40.5, p < .05). Patients in the W group received less
      fluids in the first hour compared with the P group (median and interquartile
      range 20 mL/kg, 15 and 20 vs. 30 mL/kg, 20 and 60). Fluid was actively removed
      less often in the W group than the P group (6 of 111 vs. 45 of 96, p < .05).
      There was no difference in the need for ventilation or incidence of acute
      respiratory distress syndrome between groups, although among dengue hemorrhage
      fever grade IV patients, the number requiring ventilation (17 of 30 vs. 20 of 23,
      p < .05) and the incidence of acute respiratory distress syndrome (9 of 30 vs. 17
      of 23, p < .05) were significantly greater in the W group compared with the P
      group. The duration of ventilation (1.5 +/- 1.7 vs. 4.2 +/- 2.9 days, p < .05)
      and length of intensive care unit stay (3.0 +/- 2.8 vs. 3.4 +/- 2.9 days, p <
      .05) were significantly less in the W group. The pediatric intensive care unit
      mortality (16.6% vs. 6.3%, p < .05) was significantly higher in the W group than
      in the P group. CONCLUSIONS: Patients with dengue shock syndrome are at high risk
      of mortality due to refractory shock and multiple organ failure. Survival was
      better for patients in the P group. Aggressive shock management and possibly the
      use of judicious fluid removal may decrease mortality rates in the severest forms
      of dengue shock syndrome.

PMID- 15982428
TI  - The spiritual needs of parents at the time of their child's death in the
      pediatric intensive care unit and during bereavement: a qualitative study.
AB  - OBJECTIVE: Death is common in pediatric intensive care units. A child's death can
      shatter parents' personal identities, disrupt their relationships, and challenge
      their worldviews. Spirituality is a human characteristic that engenders
      transcendence; seeks meaning, purpose, and connection to others; and helps to
      construct a coherent worldview. Greater attention to spiritual needs may help
      parents cope with their loss. Our objective is to gain a deeper understanding of
      parents' spiritual needs during their child's death and bereavement. DESIGN:
      Prospective, qualitative study. SETTING: University-affiliated children's
      hospital. PARTICIPANTS: Thirty-three parents of 26 children who died in the
      pediatric intensive care unit between January 1, 1999, and August 31, 2000.
      INTERVENTIONS: Semistructured, in-depth, videotaped interviews with parents 2 yrs
      after their child's death. MEASUREMENTS AND MAIN RESULTS: The main spiritual need
      described by parents was that of maintaining connection with their child. Parents
      maintained connection at the time of death by physical presence. Parents
      maintained connection after the death through memories, mementos, memorials, and
      altruistic acts such as organ donation, volunteer work, charitable fund raising,
      support group development, and adoption. Other spiritual needs included the need
      for truth; compassion; prayer, ritual, and sacred texts; connection with others;
      bereavement support; gratitude; meaning and purpose; trust; anger and blame; and
      dignity. CONCLUSIONS: Bereaved parents have intense spiritual needs. Health care
      providers can help to support parents' spiritual needs through words and actions
      that demonstrate a caring presence, impart truth, and foster trust; by providing
      opportunity to stay connected with the child at the time of death; and by
      creating memories that will bring comfort in the future.

PMID- 15982429
TI  - Kinetic therapy improves oxygenation in critically ill pediatric patients.
AB  - OBJECTIVE: To compare changes in oxygenation after manual turning and percussion
      (standard therapy) and after automated rotation and percussion (kinetic therapy).
      DESIGN: Randomized crossover trial. SETTING: General and cardiac pediatric
      intensive care units. PATIENTS: Intubated and mechanically ventilated pediatric
      patients who had an arterial catheter and no contraindications to using a
      PediDyne bed. INTERVENTIONS: Patients were placed on a PediDyne bed (Kinetic
      Concepts) and received 18 hrs blocks of standard and kinetic therapy in an order
      determined by randomization. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases
      were measured every 2 hrs during each phase of therapy. Oxygenation index and
      arterial-alveolar oxygen tension difference [P(A-a)O(2)] were calculated. Indexes
      calculated at baseline and after each 18-hr phase of therapy were analyzed. Fifty
      patients were enrolled. Data from 15 patients were either not collected or not
      used due to reasons that included violation of protocol and inability to tolerate
      the therapies in the study. Indexes of oxygenation were not normally distributed
      and were compared using Wilcoxon signed rank testing. Both therapies led to
      improvements in oxygenation, but only those from kinetic therapy achieved
      statistical significance. In patients receiving kinetic therapy first, median
      oxygenation index decreased from 7.4 to 6.19 (p = .015). The median P(A-a)O(2)
      decreased from 165.2 to 126.4 (p = .023). There were continued improvements in
      oxygenation after the subsequent period of standard therapy, with the median
      oxygenation index decreasing to 5.52 and median P(A-a)O(2) decreasing to 116.0,
      but these changes were not significant (p = .365 and .121, respectively). When
      standard therapy was first, the median oxygenation index decreased from 8.83 to
      8.71 and the median P(a-a)o(2) decreased from 195.4 to 186.6. Neither change was
      significant. Median oxygenation index after the subsequent period of kinetic
      therapy was significantly lower (7.91, p = .044) and median P(A-a)O(2) trended
      lower (143.4, p = .077). CONCLUSIONS: Kinetic therapy is more efficient than
      standard therapy at improving oxygenation and produces improvements in
      oxygenation that are more persistent.

PMID- 15982430
TI  - Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in
      children.
AB  - OBJECTIVE: Children often require sedation for lengthy noninvasive procedures.
      Conventional agents such as chloral hydrate, benzodiazepines, or barbiturates
      have been associated with sedation failure, respiratory depression, and paradoxic
      agitation. Dexmedetomidine is a newer alpha(2)-adrenergic receptor agonist with
      sedative properties and minimal respiratory depression. We hypothesized that it
      would be an effective agent for these procedures. DESIGN: Prospective case
      series. SETTING: Tertiary care children's hospital. PATIENTS: Children undergoing
      noninvasive procedures. INTERVENTIONS: Children were sedated with dexmedetomidine
      given as a bolus of 0.5-1.0 microg/kg over 5-10 mins followed by an infusion of
      0.5-1.0 microg/kg/hr. Vital signs, sedative effectiveness, recovery patterns, and
      complications were prospectively recorded. MEASUREMENTS AND MAIN RESULTS: Forty
      eight patients, aged 6.9 +/- 3.7 yrs, were sedated. Fifteen received
      dexmedetomidine after failing sedation with chloral hydrate and/or midazolam.
      Sedation was induced with 0.92 +/- 0.36 microg/kg over 10.3 +/- 4.7 mins and
      maintained with an infusion of 0.69 +/- 0.32 microg/kg/hr. All procedures were
      completed. Heart rate, blood pressure, and respiratory rate decreased (p < .0001)
      but remained within normal limits for age. End-tidal CO(2) exceeded 50 mm Hg in
      seven of 404 measurements (1.7%). Mean recovery time was 84 +/- 42 mins and was
      significantly longer in the rescue (117 +/- 41 mins) vs. primary (69 +/- 34 mins)
      group (p < .0001). No patient developed agitation during recovery. CONCLUSIONS:
      Dexmedetomidine provided effective sedation in children undergoing noninvasive
      procedures and represents an alternative sedative choice for this population.

PMID- 15982431
TI  - Steroid use before pediatric cardiac operations using cardiopulmonary bypass: an
      international survey of 36 centers.
AB  - OBJECTIVE: Steroid administration before pediatric cardiac operations using
      cardiopulmonary bypass has been shown to modulate the inflammatory response and
      reduce myocardial injury. We hypothesized that current steroid administration
      practices among pediatric cardiac surgical centers are highly variable. DESIGN:
      Questionnaire survey. SETTING: Pediatric intensive care units. SUBJECTS: All
      members of the Pediatric Cardiac Intensive Care Society. INTERVENTIONS: A self
      administered survey was sent to >130 members and 70 institutions participating in
      the Pediatric Cardiac Intensive Care Society. MEASUREMENTS AND MAIN RESULTS:
      Thirty-six questionnaires were returned: 14 international and 22 domestic
      centers. Cumulatively, these centers treat >11,000 pediatric cardiac patients per
      year. Ninety-seven percent (35 of 36) of these centers report the use of steroids
      before cardiopulmonary bypass, yet only 40% (14 of 35) administer steroids with
      every case. Of the 21 centers that selectively use steroids, 12 do so only for
      neonates, five administer steroids based on surgeon preference, and four
      administer steroids for cases anticipated to involve bypass time >2 hrs or deep
      hypothermic circulatory arrest. Of the 35 centers using steroids, 11 deliver a
      single dose in the circuit prime, 18 administer a single dose to the patient, and
      six give multiple doses. The timing of the steroid dose to the patient is
      variable; 12 centers administer a dose on induction of anesthesia; six centers
      administer the dose 2-12 hrs before operation. Regimens in the six centers using
      multiple doses of steroids before cardiopulmonary bypass are as follows:
      administration at induction and in the prime (two centers); 12 hrs preoperatively
      and at induction (one center); prime, induction, and 6 hrs preoperatively (one
      center); prime and midnight preoperatively (one center); and prime plus 2 and 8
      hrs preoperatively (one center). Eight centers continue steroid administration
      following bypass. CONCLUSION: Although nearly all centers surveyed administer
      steroids before cardiopulmonary bypass, the type, dosing, route, and timing of
      administration are highly variable. The inconsistencies in these data and the
      pediatric literature would support the undertaking of a large, multiple-center
      clinical trial to evaluate the risks and benefits of steroid administration
      before pediatric cardiopulmonary bypass.

PMID- 15982432
TI  - Neonates with hypoplastic left heart syndrome have ultrasound evidence of
      abnormal superior mesenteric artery perfusion before and after modified Norwood
      procedure.
AB  - OBJECTIVE: To a) describe superior mesenteric artery resistive index, as an
      estimate of perfusion, before and after modified Norwood; and b) assess incidence
      of diastolic flow reversal in the superior mesenteric artery before and after
      modified Norwood. DESIGN: Prospective observational trial. SETTING: Children's
      hospital pediatric intensive care unit. PATIENTS: Ten newborns with hypoplastic
      left heart syndrome. INTERVENTIONS: Ultrasound documentation of superior
      mesenteric artery diastolic flow direction and measurement of superior mesenteric
      artery resistive index 24-48 hrs before and 24-48 hrs after modified Norwood.
      MEASUREMENTS AND MAIN RESULTS: Seven males and three females were enrolled. There
      was no change between the superior mesenteric artery resistive index pre- vs.
      postoperatively-0.99 (95% confidence interval, 0.85, 1.12) vs. 1.07 (95%
      confidence interval, 1.0, 1.15) (p = .13). Incidence of retrograde diastolic
      blood flow in the superior mesenteric artery was not different pre- vs.
      postoperatively (70% vs. 50%, p = .41). No patients developed necrotizing
      enterocolitis and all survived to hospital discharge. CONCLUSIONS: Ultrasound
      measurements in neonates with hypoplastic left heart syndrome suggest that
      superior mesenteric artery perfusion, as measured by resistive index, is
      impaired. Superior mesenteric artery diastolic flow reversal is common before and
      immediately after modified Norwood.

PMID- 15982433
TI  - Tissue Doppler echocardiographic and color M-mode estimation of left atrial
      pressure in infants.
AB  - OBJECTIVES: Using recorded flow and tissue Doppler, we evaluated the relation of
      peak velocity of early transmitral Doppler filling (E)/early diastolic velocity
      of the lateral mitral annulus (Ea) ratio and of E/flow propagation velocity (Vp)
      ratio to mean left atrial pressure in infants after surgery for congenital heart
      disease. DESIGN: Experimental design. SETTING: Pediatric intensive care unit.
      PATIENTS: Thirty-seven infants aged 4 (3-8) months. INTERVENTIONS: Patients
      underwent postoperative invasive hemodynamic monitoring with simultaneously
      obtained Doppler measurements. MEASUREMENTS AND MAIN RESULTS: Values are
      expressed as median (25th-75th percentiles). Heart rate was 145 (135-157)
      beats/min. Left atrial pressure was 10 (8-12) mm Hg with E/Ea 16 (12-19) and E/Vp
      1.9 (1.3-2.4). E/Ea and E/Vp ratios were higher in patients with left atrial
      pressure >10 mm Hg (n = 18), than in patients with left atrial pressure < or =10
      mm Hg (n = 19) (E/Ea, 16 [15-25] vs. 12 [9-17], p = .01; E/Vp, 2.3 [1.9-2.8] vs.
      1.4 [1-1.9]. respectively, p = .001). At a cutoff point of 15, E/Ea sensitivity
      for left atrial pressure >10 mm Hg was 17 of 18 (94%) with specificity 13 of 18
      (72%). At a cutoff point of 2, E/Vp sensitivity for left atrial pressure >10 mm
      Hg was 15 of 18 (83%) with specificity 16 of 18 (89%). Areas under the receiver
      operating characteristic curves were 0.76 (E/Ea) and 0.83 (E/Vp). CONCLUSIONS:
      Doppler ratios might be considered as promising noninvasive tools for left atrial
      pressure evaluation in infants after cardiac surgery.

PMID- 15982434
TI  - Utility of airway exchange catheters in pediatric patients with a known difficult
      airway.
AB  - OBJECTIVE: To evaluate the utility of the Cook airway exchange catheter (CAEC)
      for extubation/reintubation in pediatric patients with a known difficult airway.
      DESIGN: Prospective, nonrandomized. SETTING: Pediatric intensive care unit;
      single academic institution. PATIENTS: Twenty intubated children </=18 yrs of age
      with a known difficult airway requiring extubation. INTERVENTIONS: The CAEC was
      inserted into the trachea before extubation in children with a known difficult
      airway who were at risk for a difficult reintubation. The CAEC provided a means
      of a "guided" reintubation while maintaining the ability to provide supplemental
      oxygenation directly into the trachea. MEASUREMENTS AND MAIN RESULTS: The
      respiratory rate, oxygen saturation, and amount of oxygen administered were
      measured immediately before extubation and at 5-, 15-, 30-, and 60-min intervals
      thereafter. In addition, the child's ability to tolerate the CAEC was noted and
      rated (0 = tolerable without difficulty, 1 = tolerable with difficulty, 2 =
      intolerable). No sedatives were administered in the presence of the CAEC. The
      duration of the CAEC placement was dependent on the satisfaction of the child's
      airway patency as determined by the unlikely need for reintubation. Five of the
      20 (25%) children who had been extubated were reintubated in the intensive care
      unit with the assistance of the CAEC. Three of the five (60%) children were
      reintubated for upper airway obstruction. The ability to provide supplemental
      oxygen through the CAEC into the trachea during reintubation diminished the
      potential for hypoxia and maintained the ability to reintubate the trachea using
      the CAEC as a guidewire to pass an endotracheal tube. CONCLUSIONS: In children
      with a known difficult airway who are at risk for a difficult reintubation, the
      CAEC is a useful tool for a trial of extubation in the intensive care unit.

PMID- 15982435
TI  - Gram-negative bacilli associated with catheter-associated and non-catheter
      associated bloodstream infections and hand carriage by healthcare workers in
      neonatal intensive care units.
AB  - OBJECTIVE: Bloodstream infections caused by Gram-negative bacilli are a
      substantial cause of morbidity and mortality in infants in neonatal intensive
      care units. This study describes the species of Gram-negative bacilli causing
      bloodstream infections in two neonatal intensive care units, compares
      characteristics of catheter-related and non-catheter-related bloodstream
      infections, and compares species and antibiotic resistance patterns of these
      organisms with those isolated from the hands of nurses working in the same
      neonatal intensive care units. DESIGN: Interventional study. SETTING: Two high
      risk neonatal intensive care units. PATIENTS: Neonates hospitalized for >or =24
      hrs. INTERVENTIONS: Prospective surveillance for bloodstream infections was
      performed in two neonatal intensive care units from March 2001 to January 2003.
      Hand cultures were obtained quarterly from participating nurses immediately after
      they performed hand hygiene. MEASUREMENTS AND MAIN RESULTS: There were 298
      episodes of bloodstream infections among 2,935 admissions (5.75 episodes per
      1,000 patient-days); 77 of 298 (26%) episodes were caused by Gram-negative
      bacilli. Among these, 47 (61.0%) were catheter-related bloodstream infections
      (2.61 episodes per 1,000 catheter-days). Eleven and 24 Gram-negative bacilli
      species were isolated from neonates and nurses, respectively. The most common
      Gram-negative bacilli causing bloodstream infections were Klebsiella pneumoniae
      (38.7%), Escherichia coli (21.2%), Enterobacter cloacae (11.2%), and Serratia
      marcescens (11.2%). In contrast, Acinetobacter lwoffi (18.1%), K. pneumoniae
      (11.7%), E. cloacae (10.6%), K. oxytoca (10.6%), and Pseudomonas spp. (7.4%) were
      most commonly isolated from hands of nurses. E. coli, P. aeruginosa, E. cloacae,
      and E. aerogenes were significantly more likely to cause bloodstream infections
      than to be isolated from nurses' hands (all p < .001). Although 39% of
      bloodstream infections were non-catheter-related, there were no significant
      differences in types of organisms or antimicrobial resistance patterns between
      catheter-related bloodstream infections and non-catheter-related bloodstream
      infections (all p > or = .35). Resistance patterns were similar between Gram
      negative bacilli isolates from neonates and nurses' hands except for a
      significantly higher proportion of resistance to cefotaxime and gentamicin among
      neonatal isolates of K. pneumoniae (p < .05). CONCLUSIONS: Gram-negative bacilli
      species isolated from neonatal bloodstream infections and nurses' hands varied
      significantly. Clean hands of providers are an unlikely source of endemic Gram
      negative bacilli, suggesting that prevention strategies should focus more on
      control of endogenous neonatal flora or environmental sources.

PMID- 15982436
TI  - In vitro evaluation of bronchodilator drug delivery by jet nebulization during
      pediatric mechanical ventilation.
AB  - OBJECTIVE: To determine the influence of jet nebulizer brands and nebulization
      mode on albuterol delivery in a mechanically ventilated pediatric lung model.
      DESIGN: In vitro, laboratory study. SETTING: Research laboratory of a university
      hospital. INTERVENTIONS: Using albuterol as a marker, six jet nebulizers
      (Microneb NA420, Sidestream, Acorn II, Cirrus, Upmist, Micro Mist) were tested in
      four nebulization modes in a bench model mimicking the ventilatory pattern of a
      10-kg infant (Galileo ventilator, Hamilton Medical). The amounts of albuterol
      deposited on the inspiratory filters at the end of the endotracheal tube were
      determined, as well as the pressure, flow profiles, and particle size
      distribution of the jet nebulizers. MEASUREMENTS AND MAIN RESULTS: Pooling the
      data of the six jet nebulizer brands (n = 30) indicated that intermittent
      nebulization during the expiratory phase was more efficient (6.5 +/- 2.5% of the
      initial dose, p < .001) than intermittent nebulization during the inspiratory
      phase (1.9 +/- 1.2%) and continuous nebulization with air from the ventilator
      (4.0 +/- 1.5%) or from an external source (4.2 +/- 1.4%). The particle size
      distribution at 6 L x min(-1) was between 2.81 and 3.30 microm. CONCLUSIONS: In
      our in vitro pediatric lung model, the quantity of inhaled drug was low. Jet
      nebulizer brands and nebulization modes significantly affected drug delivery, and
      in vitro models designed for adults cannot be extrapolated to infants.

PMID- 15982437
TI  - Glucose level and risk of mortality in pediatric septic shock.
AB  - OBJECTIVE: To study the relationship between serum glucose level and mortality in
      children with septic shock. DESIGN: Prospective cohort study. SETTING: Twelve-bed
      pediatric intensive care unit at the Hospital Sao Lucas da PUCRS, Porto Alegre,
      Brazil. PATIENTS: All children admitted with septic shock refractory to fluid
      therapy over a period of 32 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Serum glucose levels were measured in all children during the study
      period, and the highest value was assessed in relation to outcome. Fifty-seven of
      1,053 children admitted to the intensive care unit were enrolled in the study.
      The peak glucose level in those with septic shock was 214 +/- 98 mg/dL (mean +/-
      SD), and the mortality rate was 49.1% (28/57). In nonsurvivors, the peak glucose
      level was 262 +/- 110 mg/dL, which was higher (p < .01) than that found in
      survivors (167.8 +/- 55 mg/dL). The area under the receiver operator curve for
      peak glucose level and mortality rate was 0.754. The best peak glucose level for
      predicting death in children with sepsis was 178 mg/dL (sensitivity, 0.714;
      specificity, 0.724), and the relative risk of death in patients with peak glucose
      levels of > or =178 mg/dL was 2.59 (range, 1.37-4.88). CONCLUSION: In children
      with septic shock, a peak glucose level of >178 mg/dL is associated with an
      increased risk of death.

PMID- 15982438
TI  - Recombinant factor VII for severe bleeding during extracorporeal membrane
      oxygenation following open heart surgery.
AB  - OBJECTIVES: Severe bleeding is a recognized complication during mechanical
      cardiopulmonary support with extracorporeal membrane oxygenation. We present the
      use of recombinant activated factor VII (rFVIIa) for severe, refractory bleeding
      during extracorporeal membrane oxygenation support after open-heart surgery for
      congenital heart disease. DESIGN: Retrospective review of all patients receiving
      rFVIIa on extracorporeal membrane oxygenation. SETTING: A pediatric
      extracorporeal membrane oxygenation center located within the cardiac intensive
      care unit of a tertiary care children's hospital. PATIENTS: Four patients treated
      with rFVIIa for refractory bleeding on extracorporeal membrane oxygenation.
      INTERVENTIONS: The patients received rFVIIa for severe, refractory blood loss
      despite applying clotting products and aprotinin infusion and excluding surgical
      reasons. MEASUREMENTS AND MAIN RESULTS: rFVIIa was given 4-7 hrs after commencing
      extracorporeal membrane oxygenation; a second identical dose was administered 4
      hrs later. Bleeding decreased significantly in all patients within 30 mins after
      the first dose of rFVIIa; no side effects were observed. CONCLUSIONS: rFVIIa is
      effective to achieve control of refractory hemorrhage in patients on
      extracorporeal membrane oxygenation. Now a randomized controlled trial to
      evaluate risks and benefits of rFVIIa on patients undergoing extracorporeal
      membrane oxygenation is required.

PMID- 15982440
TI  - Coma and respiratory failure in a child with severe vitamin B(12) deficiency.
AB  - OBJECTIVE: Psychofunctional follow-up of severe vitamin B(12) deficit. DESIGN:
      Case report. SETTING: Pediatric intensive care unit. PATIENT: Ten-month-old boy.
      INTERVENTION: Follow-up at 3 yrs. MEASUREMENTS AND MAIN RESULTS: A 10-month-old
      boy was admitted to the pediatric intensive care unit with respiratory failure,
      muscular hypotonia, and involuntary movements. Although a central nervous system
      infection was excluded, computed tomography scan showed a diffuse cortical
      subcortical atrophy. Vitamin B(12) deficiency was suspected because of a red-cell
      count of 1,350,000/mm(3) and a hemoglobin value 5.9 g/dL (MCV 116). The baby had
      been exclusively breast-fed, but his mother had been a strict vegan for 10 yrs.
      Chronic dietary vitamin B(12) deprivation was confirmed by blood and urinary
      samples. Treatment with vitamin B(12) led in 2 wks to rapid and complete
      hematological improvement and to partial regression of neurologic symptoms.
      During the following 3 yrs the boy had normal vitamin intake and underwent
      intensive rehabilitative treatment. The brain atrophy regressed, but linguistic
      and psychomotor delay persisted. CONCLUSIONS: Rapid clinical improvement after
      vitamin supply does not correlate with a complete recovery.

PMID- 15982439
TI  - Critical appraisal of Perez et al: Jugular venous oxygen saturation or
      arteriovenous difference of lactate content and outcome in children with severe
      traumatic brain injury.
AB  - OBJECTIVE: To review the findings and discuss the implications of jugular venous
      bulb oxygenation monitoring in children with severe traumatic brain injury.
      DESIGN: A critical appraisal of Perez et al, Jugular venous oxygen saturation or
      arteriovenous difference of lactate content and outcome in children with severe
      traumatic brain injury. FINDINGS: Two episodes of jugular venous bulb
      desaturation and abnormal values of arteriovenous difference in lactate content
      are associated with poor neurologic outcome in children with severe traumatic
      brain injury-risk ratio 6.6 (95% confidence interval, 1.5-29.7) and risk ratio
      17.6 (95% confidence interval, 2.5-122.5), respectively. This confirms the
      findings of previously reported adult studies. CONCLUSIONS: This study is the
      first to demonstrate that jugular venous monitoring may aid in predicting the
      neurologic outcome of children with severe traumatic brain injury. More studies
      need to be performed (particularly on safety) before adopting jugular venous bulb
      oxygenation monitoring as a prediction tool or, ultimately, as a therapeutic
      intervention to help manage and improve outcome for children with severe
      traumatic brain injury.

PMID- 15982441
TI  - Cardiopulmonary resuscitation of a near-drowned child with a combination of
      epinephrine and vasopressin.
AB  - OBJECTIVE: To report a cardiopulmonary resuscitation attempt in a 20-month-old
      child employing a combination of vasopressin and epinephrine. DESIGN: Case
      report. SETTING: Out-of-hospital cardiopulmonary resuscitation. PATIENT: A 20
      month-old child found in cardiac arrest after submersion. INTERVENTIONS AND
      RESULTS: Dispatcher-assisted basic life support was initiated immediately after
      pulling the child out of the water. The emergency medical service crew arrived
      approximately 6 mins later and found a hypothermic, cyanotic child in
      cardiocirculatory arrest. The first electrocardiogram showed sinus bradycardia.
      After intubation and administration of epinephrine and atropine with no effect,
      an intravenous bolus of 0.2 mg of epinephrine and 10 IU of vasopressin resulted
      in restoration of spontaneous circulation. The boy was flown to a hospital and
      was discharged 23 days later to a rehabilitation facility. He returned home 6
      months after the accident, where further rehabilitation efforts are pending.
      CONCLUSION: Bystander cardiopulmonary resuscitation, early and aggressive
      advanced life support, rewarming, and the combination of intravenous epinephrine
      and vasopressin were associated with sustained return of spontaneous circulation
      following hypothermic submersion-associated cardiac arrest.

PMID- 15982442
TI  - Ventilation in pediatric diabetic ketoacidosis--not too much, but not too little.

PMID- 15982443
TI  - Long-term outcome of meningococcal sepsis-associated acute renal failure.
AB  - SETTING: Twenty-one of 209 children admitted to the intensive care unit with
      meningococcal septicemia developed oliguric acute renal failure necessitating
      renal replacement therapy. PATIENTS: Twelve survivors underwent renal assessment
      at a median of 4.2 yrs postpresentation. RESULT: Two had abnormal glomerular
      filtration rate, proteinuria, and hypertension; one had isolated proteinuria; and
      one had an isolated renal parenchymal defect on DMSA scan. CONCLUSION: Long-term
      follow-up of this population is recommended.

PMID- 15982444
TI  - Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive
      compulsive disorder (OCD) and Tourette's syndrome (TS).
AB  - There is evidence that motor and premotor cortex are hyperexcitable in obsessive
      compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low
      frequency repetitive transcranial magnetic stimulation (rTMS) could normalize
      overactive motor cortical regions and thereby improve symptoms. Subjects with OCD
      or TS were treated with active rTMS to the supplementary motor area (SMA) for 10
      daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of
      clinical improvement were apparent as early as the first week of rTMS. At the
      second week of treatment, statistically significant reductions were seen in the
      YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement
      was correlated with a significant increase of the right resting motor threshold
      and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant
      clinical improvement and a normalization of the right hemisphere
      hyperexcitability, thereby restoring hemispheric symmetry in motor threshold.

PMID- 15982445
TI  - Altered gene expression in mice treated with the mood stabilizer sodium
      valproate.
AB  - Valproate is now the most widely prescribed mood-stabilizing drug and is being
      used increasingly in the treatment of bipolar disorder. However, the mechanism of
      action for valproate remains unclear. Microarray analysis was used to identify
      genes and cellular pathways that are affected in the mouse brain after treatment
      with valproate at human therapeutic concentrations. This study has identified 11
      genes that are differentially expressed by >or=2-fold when compared to control
      untreated mice. Altered expression of four of these genes was also validated by
      quantitative PCR analysis. Valproate was found to significantly decrease the
      expression of zinc finger protein of the cerebellum 1 (ZIC1) and increase the
      expression of Scm-related gene containing four mbt domains (SFMBT2), structural
      maintenance of chromosome 4-like 1 (SCM4L1), and prostate apoptosis response-4
      (PAR-4). Many of the genes identified are involved in the development and
      function of the brain. These results indicate that valproate regulates a large
      number of different functional pathways in the brain. Understanding the molecular
      and cellular mechanisms by which valproate achieves its therapeutic action
      represents a valuable step in clarifying the pathophysiology of bipolar disorder.

PMID- 15982446
TI  - Prefrontal grey-matter changes in short-term and long-term abstinent
      methamphetamine abusers.
AB  - Authors explored grey-matter density in 29 methamphetamine abusers and 20 healthy
      comparison subjects using voxel-based morphometry. Grey-matter density changes
      and performances on the Wisconsin Card Sorting test (WCST) were also compared
      between 11 short-term (<6 months) and 18 long-term (>or=6 months) abstinent
      methamphetamine abusers. Methamphetamine abusers had lower grey-matter density in
      the right middle frontal cortex (corrected p<0.05) and more total errors in the
      WCST (p<0.01) relative to healthy comparison subjects. Grey-matter density
      decrease in the right middle frontal cortex correlated with total errors in the
      WCST in methamphetamine abusers (r=-0.45). Long-term abstinent abusers had
      significantly less right middle frontal grey-matter density decrease (p<0.01) and
      total errors in the WCST (p<0.01) than short-term abstinent abusers, but more
      than the healthy comparison subjects. We report that methamphetamine abusers have
      prefrontal grey-matter deficit, which may, in part, recover with long-term
      abstinence.

PMID- 15982447
TI  - Effect of amantadine and imipramine on immunological parameters of rats subjected
      to a forced swimming test.
AB  - The activation of cell-mediated immunity and the hypothalamic-pituitary-adrenal
      axis may play a role in the pathophysiology of depression, especially a treatment
      resistant one, and antidepressant treatments may exert their effect by
      suppressing this activation. In our previous studies we described synergistic,
      antidepressant-like effects of a combination of amantadine (10 mg/kg) and
      imipramine (5 mg/kg) - drugs otherwise ineffective when given separately in such
      doses - in the forced swimming test (FST), an animal model of depression.
      Moreover, preliminary clinical data show that the above-described combination has
      beneficial effects on treatment-resistant patients. However, it is still unknown
      whether these positive effects of combined treatment with amantadine and
      imipramine on behavioural depressive changes are accompanied with normalization
      of immunoendocrine parameters. Therefore, the present study was aimed at
      ascertaining whether the antidepressive effect of a combination of amantadine and
      imipramine was accompanied with a decrease in some immunoendocrine parameters.
      The antidepressant activity was accompanied with a reversal of the stress-induced
      increase in the proliferation of splenocytes in response to concanavalin A
      (ConA). Imipramine, amantadine and a combination of amantadine and imipramine
      enhanced the production of the negative immunoregulator IL-10 in rats subjected
      to the FST. The exposure to the FST produced an increase in plasma corticosterone
      levels, which was significantly attenuated by pretreatment with imipramine or
      amantadine (a combination of imipramine and amantadine causes reduction within
      the margin of error). In summary, the antidepressive efficacy of a combination of
      amantadine and imipramine given in suboptimal doses may be related to their
      negative immunoendocrine effects.

PMID- 15982448
TI  - Positive association of AKT1 haplotype to Japanese methamphetamine use disorder.
AB  - Recent evidence suggests that the AKT1-GSK3beta signalling cascade partially
      mediates dopamine-dependent behaviours. In relation to the pathophysiology of
      schizophrenia or methamphetamine (Meth) use disorder, AKT1 is a good candidate
      gene for such conditions. For schizophrenia, positive associations of SNPs and
      AKT1 haplotypes were reported in US and Japanese samples. To evaluate the
      association between AKT1 and Meth-use disorder, we conducted a case-control study
      of Japanese samples (182 patients and 437 controls). A positive association
      between a SNP and haplotypes was found, and the 'signal' SNP was the same SNP
      found to be associated with US schizophrenia, but not with Japanese
      schizophrenia. Our results indicate that AKT1 may play a possible role in the
      development of Meth-use disorder. Further investigation of these associations,
      together with evidence from previous animal studies, may open the way to
      elucidation of the pathophysiology of this condition.

PMID- 15982449
TI  - Reproduction in vertebrates and man. Symposium in honor of Professor Charles
      Thibault. 18-19 March 2004, Paris, France.

PMID- 15982450
TI  - The zootechnical applications of biotechnology in animal reproduction: current
      methods and perspectives.
AB  - The development of the four generations of Reproductive Biotechnology,
      particularly in cattle and since the last world war, represents one of the best
      examples of the success story of technology transfer. This review will only refer
      to the first three generations and will not deal with nuclear transfer nor
      transgenesis. Based on sound so-called "finalised" research, Artificial
      Insemination first, then in vivo collected embryo transfer and later in vitro
      fertilised embryo transfer have been implemented worldwide. Each of these
      Biotechnologies has many advantages and limitations. In addition to the
      specificity of each of them, one major point is that farmers and breeders may
      choose either collectively or individually, the best technology to be used in
      order to achieve the goals they have set for their industry. It is noteworthy
      that these technologies have been able to match with the economics demands over
      the last decades and yet are in a very good capacity to respond to the
      contemporary demand of sustainable development. In this context, there are
      further advantages such as potentially contributing to maintaining biodiversity
      or allowing preservation ex situ of genes otherwise threatened to extinction.

PMID- 15982451
TI  - Gonadotropin-releasing hormone and the control of gonadotrope function.
AB  - Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile
      release of hypothalamic GnRH that binds high-affinity receptors present at the
      surface of pituitary gonadotrophs thereby triggering the synthesis and release of
      the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical
      heptahelical structure of G protein-coupled receptors with, however, a unique
      feature, the lack of a C-terminal tail. Accordingly, it does not desensitise
      sensu stricto, and internalises very poorly. It is now well established that GnRH
      stimulation induces the activation of a complex network of transduction pathways
      involved in the control of gonadotropin release and subunit gene expression.
      Other authors and ourselves have demonstrated that the GnRH action is associated
      with an increased complexity regarding gene regulation/cell function. Indeed GnRH
      affects the GnRH receptor gene itself and a number of additional genes that
      include some involved in cell signalling and auto-/paracrine regulation. The fact
      that GnRH regulates the expression of its own receptor, together with a host of
      other genes typically involved in its signal transduction cascades implies
      alteration/auto-adaptation in gonadotropic responsiveness. Furthermore, some of
      these genes respond differentially depending on whether the GnRH stimulation is
      intermittent or permanent suggesting specific roles in the dual process of
      activation/desensitisation. Thus, it can be assumed that the importance of
      pulsatility of GnRH action is closely related to, or dependent on, the inability
      of the GnRH receptor to desensitise. Moreover, multiple post-receptor events are
      crucial for both the regulation/plasticity of gonadotropic function and the
      maintenance of cell integrity.

PMID- 15982452
TI  - Involvement of equine chorionic gonadotropin (eCG) carbohydrate side chains in
      its bioactivity; lessons from recombinant hormone expressed in insect cells.
AB  - Natural eCG consists of as much as 45% carbohydrate side chains. The present
      paper deals with the analysis of the roles of the N- and O-linked saccharides of
      this hormone in the different steps of its activity and its possible replacement
      by recombinant eCG expressed in baculovirus-insect cell systems.

PMID- 15982453
TI  - Particularities of reproduction and oogenesis in teleost fish compared to
      mammals.
AB  - Compared to mammals, teleost reproduction presents many original features.
      Reproductive strategies of species are diversified into numerous adaptations to a
      large variety of aquatic environments. This diversity may concern sexuality,
      spawning and parental behaviour, sensitivity to environmental factors, and
      specific features of gametogenesis such as the duration of vitellogenesis, and
      egg morphology. Sexuality presents a variety of natural modalities, from
      gonochorism to hermaphrodism. The absence of definitive arrest of body growth in
      the adult of most species gives a particular interest to the practical control of
      growth-reproduction interactions. Vitellogenesis, which represents an important
      metabolic effort for the maternal organism, involves the synthesis of
      vitellogenin, a specific glycolipo-phosphoprotein produced in the liver under
      estradiol stimulation, and its incorporation into oocytes by a receptor mediated
      process. Both estradiol synthesis in follicle cells and vtg uptake by
      vitellogenic follicles appear to be mainly controlled by FSH. Oocyte maturation
      is directly triggered by a progestin, or MIS (maturation inducing steroid)
      synthesised in follicle cells mainly under LH control, and acting through the non
      genomic activation of a membrane receptor. Practical applications of some of
      these particularities result mainly from the external character of the
      fertilisation process and of embryonic development, which allows manipulating
      respectively egg chromosome stocks and sex differentiation. Moreover, the
      sensitivity of sex differentiation to exogenous factors favours the development
      of practical methods to control the sex of farmed populations. Finally, the
      sensitivity of reproductive mechanisms to xenobiotics has led to various kinds of
      bioassays for putative pollutants.

PMID- 15982454
TI  - The Fallopian tubes in domestic mammals: how vital is their physiological
      activity?
AB  - Set in an historical perspective, this essay examines diverse physiological
      aspects of Fallopian tube function in domestic animals and man. Microsurgical
      experiments are described that established the role of the isthmus in imposing a
      sperm gradient up to the site of fertilisation. Resection of the isthmus followed
      by reanastomosis of the remaining portions of the tube generated a high incidence
      of polyspermy in mated animals. Scanning electron microscopy and surgical studies
      revealed that spermatozoa were arrested and stored in the caudal portion of the
      isthmus before ovulation, the so-called functional sperm reservoir. There were
      specific adhesion contacts between the sperm head and endosalpingeal microvilli
      or cilia. Further experiments indicated that very large numbers of competent
      spermatozoa could be released from pre-ovulatory binding by microinjections of a
      solution of progesterone in oil under the serosal layer of the tube: when
      suitably timed, such treatment led to a high incidence of polyspermic
      fertilisation. Avid sperm binding in the caudal isthmus before ovulation prevents
      myosalpingeal activity leading to abnormal fertilisation, as might occur with
      multiple mating. Temperatures in the reproductive system were assessed and the
      caudal isthmus was found to be cooler than the ampulla during the pre-ovulatory
      phase of sperm storage. Finally, the existence of fluid microenvironments within
      the Fallopian tubes was reported, and the role of suspended cumulus-corona cells
      in amplifying signals from the zygote examined. An impact of Fallopian tube
      fluids on embryonic gene expression was also considered--an influence that may be
      further imposed if such fluids have access to the uterine lumen.

PMID- 15982455
TI  - Charles Thibault and assisted reproduction in France.
AB  - Charles Thibault was liked by French gynaecologists. There was not a year that
      Charles Thibault did not attend clinician gynaecology conferences. He made great
      strides in research on in vitro fertilisation, being the first to perform in
      vitro fertilised (IVF) oocyte transfers in rabbits. Later, in 1978 the first
      human pregnancy following IVF was achieved in the UK when Louise Brown was born.
      In 1980, two French teams,one at the Sevres hospital and the other at the Clamart
      University Teaching Hospital, carried out egg retrievals in patients with natural
      cycles, after determination of the urinary LH peak, under general anaesthesia and
      by laparoscopy. The Clamart team developed LH SIR, which enabled a more accurate
      determination of the ideal time for egg collection. In 1983, the same team
      reported the first ambulatory oocyte retrievals by ultrasound, under local
      anaesthesia. This new technique did not require general anaesthesia. Finally, in
      1983, the rate of births, per transfer, for the Sevres team rose to 5.31%. 1984
      showed considerable improvement: 13.83%. The first step in establishing IVF in
      France was completed with the Carghese symposium, in September 1984, where
      Charles Thibault pleaded for animal experimentation before human clinical trials.
      It was only later that ART developed significantly, necessitating a legislative
      framework and organisations such as GEFF and FIVNAT.

PMID- 15982456
TI  - An astonishing journey into reproductive genetics since the 1950's.
AB  - Training in genetics in Edinburgh in the 1950s led to a PhD on the developmental
      biology of mouse embryos with unusual chromosomal complements. Fundamental
      aspects of reproduction under study included ovulation induction, oocyte
      maturation and embryonic growth to blastocysts. It led to the introduction of
      embryo stem cells, preimplantation genetic diagnosis, the exact timing of human
      oocyte maturation in vitro and studies on fertilising human eggs in vitro to
      alleviate human infertility. My work was helped by studies on sperm capacitation
      and the physiology of fertilization in domestic and laboratory species by
      Thibault, Dauzier, Austin, Chang, Yanagimachi and others. I met Charles Thibault
      at a meeting in Cambridge U.K. where he criticised the work of Moricard, and then
      frequently on lecture circuits. Impressed by his grandeur but not his doubts
      about human IVF, Steptoe and I initiated human embryo transfers and the birth of
      Louise Brown. Details of her pregnancy had to be confidential to reduce the risks
      of abortion associated with the intrusion of numerous newsmen chasing the story.
      I was compelled to withold this information at a meeting in Paris in the late
      1960s when I had to leave early to return to UK. This omission annoyed Thibault
      and led to our celebrated quarrel. I felt he failed to appreciate the complexity,
      the implications of this pregnancy and an astonishing future. So much was at
      stake, including IVF, stem cells and preimplantation diagnosis to help millions
      of patients. Some months later, our dispute was ended even if somewhat formally.
      Nevertheless it is a pleasure to recall how we shared so much in common. I still
      admire him as an inspiration to many colleagues and students, and a father figure
      in French agricultural research.

PMID- 15982457
TI  - From transgression to pragmatism in reproductive medicine.
AB  - It is difficult to harmonise faith and the desire to follow religious teachings
      and obligations on the one hand, and scientific advances and their use for the
      benefit of suffering humanity on the other. This is an especially delicate matter
      for patients and health professionals in reproductive medicine. It deals with the
      conflicting issues of contraception, termination of pregnancy, assisted
      reproduction, cloning, stem cells and embryo research. Beyond the technical
      aspects of these matters, the theoretical, legal, philosophical and religious
      implications must be explored, including the concepts of personality,
      individuality, human dignity, autonomy, beneficence and justice. Most
      importantly, an analysis must be made of the beginnings of a human being, the
      protection it deserves, the concept and time of ensoulment, the need for
      pragmatism and the right of transgression (hence the title of this article).

PMID- 15982458
TI  - Methods in clonal analysis and applications.
AB  - During development, embryonic cells display a large variety of behaviors that
      lead to the formation of embryonic structures that are frequently transient.
      Simultaneously, cells progress towards a specific fate. The current challenge for
      embryologists is to resolve how these two distinct aspects of development co
      exist. As cell behaviors (including elementary cellular operations such as
      motility, adhesiveness, polarization, change in shape, division and death) and
      their control are much less well understood than the genetic aspects of cell fate
      determination, there is currently much interest in the study of cell behaviors.
      This mainly consists of labeling groups of cells or, less frequently, single
      cells and observing their descendants. In this review, we describe a few
      techniques for labeling groups of cells and we discuss prospective and
      retrospective clonal analysis, in particular the LaacZ system, in detail. We
      examine the information generated by these approaches.

PMID- 15982459
TI  - Mechanisms of activation of maternal behaviour in mammals.
AB  - In mammals, the activation of maternal behaviour depends on internal maternal
      factors related with parturition. The nature of these factors may vary between
      species, although oestradiol, foetus expulsion and intracerebral oxytocin are the
      most commonly encountered. They induce a period of specific receptivity to some
      sensory cues provided by the neonate. These cues (tactile, olfactory, auditory,
      ...) also vary between species. The interactions between the mother and her
      progeny during this period, known as the sensitive period, facilitate the
      maintenance of maternal responsiveness beyond the initial phase of activation by
      the factors internal to the mother. The ability of mothers to display a well
      adapted maternal behaviour is also modulated by maternal experience gained at the
      first parturition. Furthermore, this capacity is also influenced by the nature of
      the interactions experienced in infancy with the own mother of the female, which
      can lead to a non-genomic transmission of some individual characteristics of
      maternal behaviour or sensitivity to stress across generations.

PMID- 15982460
TI  - Nuclear transfer: a new tool for reproductive biotechnology in cattle.
AB  - Recent evolutions of somatic cloning by nuclear transfer are reported, especially
      in the bovine species where potential applications are underway for biomedicine
      in association with transgenesis, or for agriculture by improving livestock. The
      overall efficiency of this biotechnology remains low in terms of viable
      offspring, but significant progress has been achieved on the different steps of
      the technique. However, the in vivo development of bovine blastocysts derived
      from somatic nuclear transfer is characterised by some important features that
      lead to the "cloning syndrome". Important losses occur during the peri
      implantation period and further late foetal loss is observed in association with
      the Large Offspring Syndrome. About 60-70% of the cloned calves born survive
      normally to the adult stage and present an apparently normal physiology. Recent
      data already available on bovine somatic clones of both sexes indicate that they
      have a zootechnical performance similar to non cloned animals and they are able
      to reproduce normally without the pathologies associated to cloning thus
      confirming that the deviations observed in clones are of epigenetic origin and
      not transmitted to the progeny.

PMID- 15982461
TI  - Relations between animal transgenesis and reproduction.
AB  - Transgenesis has become an essential tool for the study of gene expression
      mechanisms and functions. Transgenesis is also more and more used for
      biotechnological applications such as the study of human diseases, the adaptation
      of pig organs to humans, the production of pharmaceutical proteins in milk and
      likely in the future for the improvement of animal production. The use of
      transgenesis relies on the efficiency of gene transfer. New tools have been
      recently designed to improve gene transfer. The methods of gene transfer are
      highly dependent on the techniques of animal reproduction. Conversely, the need
      to improve transgenesis urges researchers to study some of the key steps in
      reproduction and to find new techniques for gene transfer. This paper summarises
      the recent data and the perspectives offered by animal transgenesis.

PMID- 15982462
TI  - Foxl2 gene and the development of the ovary: a story about goat, mouse, fish and
      woman.
AB  - In this review, we describe recent results concerning the genetics of sex
      determination in mammals. Particularly, we developed the study of the FOXL2 gene
      and its implication in genetic anomalies in goats (PIS mutation) and humans
      (BPES). We present the expression of FOXL2 in the ovaries of different species.

PMID- 15982463
TI  - Homage to Professor Charles Thibault. Synthesis of the symposium and conclusions.
AB  - "Reflexive biology", using the ambiguities of the term, is altogether a biology
      that plays with the mirrors of the different levels of organisation, which,
      endlessly, go from one place to another, organisms in their real environment to
      the genome via cells in vitro and others, but which is also reflexive because at
      any moment biology reflects the finalities and the worry of what it should serve.

PMID- 15982464
TI  - The effect of a training course in aggression management on mental health nurses'
      perceptions of aggression: a cluster randomised controlled trial.
AB  - Nurses' attitudes towards patient aggression may influence their behaviour
      towards patients. Thus, their enhanced capacity to cope with aggressive patients
      may nurture more positive attitudes and alleviate adverse feelings emanating from
      patient aggression. This cluster randomised controlled trial conducted on six
      psychiatric wards tested the hypotheses that a 5 day training course in
      aggression management would positively influence the following outcome measures:
      Nurses' perception and tolerance towards patient aggression and resultant adverse
      feelings. A repeated measures design was employed to monitor change. No effect
      was found. The short time frame between the training course and the follow up
      measurement or non-responsiveness of the measurement instruments may explain this
      finding.

PMID- 15982465
TI  - Assessing nurse-patient interactions from a caring perspective: report of the
      development and preliminary psychometric testing of the Caring Nurse--Patient
      Interactions Scale.
AB  - While there is a large body of literature regarding caring in nursing and some
      measurement tools addressing the concept have been developed, limitations of
      existing instruments constrain theory-driven research on nurse-patient
      interactions. The purpose of this paper is to describe the development and
      initial psychometric evaluation of the Caring Nurse-Patient Interactions Scale in
      a sample of 332 nurses and nursing students. The tool intended to facilitate
      research on the links between caring and patient outcomes. A content validity
      approach involving 13 expert nurses resulted in a 70-item tool sub-divided into
      10 nursing carative factors. Alpha coefficients between sub-scales varied from
      .73 to .91 and sub-scales inter-correlations ranged from .53 to .89. Pearson
      correlation coefficients ranged from --.02 to .32 between the sub-scales and
      social desirability suggesting low to moderate bias. Results of the contrasted
      group approach partially supported the hypotheses while all differences were in
      the expected direction. Results suggest that the scale has strong potential for
      use in research, clinical and educational settings.

PMID- 15982466
TI  - Assessing role activities of individuals receiving long-term hemodialysis:
      psychometric testing of the revised Inventory of Functional Status-Dialysis (IFS
      Dialysis).
AB  - The purpose of the study was to examine the reliability and validity of the
      revised IFS-Dialysis, a theory-based self-report measure of the extent to which
      individuals receiving long-term hemodialysis are actually performing role
      activities. The IFS-Dialysis was administered to 186 individuals receiving
      hemodialysis. Chronbach's alpha was used to assess internal consistency
      reliability, and structural equation modeling was used to assess the construct
      validity of the revised measure. Alpha reliability for the total instrument was
      0.88, and subscale alpha coefficients ranged from 0.75 to 0.85. Construct
      validity of the IFS-Dialysis was supported by the significant relationship of
      each item to its respective subscale latent variable, and model testing indicated
      a good fit of the measurement model to the data. The IFS-Dialysis can be used to
      obtain clinical assessments of the extent to which individuals receiving long
      term hemodialysis treatments are engaging in role activities. Interventions can
      then be implemented to facilitate an optimal level of activity performance for
      each individual.

PMID- 15982467
TI  - Knowing and doing phenomenology: the implications of the critique of 'nursing
      phenomenology' for a phenomenological inquiry: a discussion paper.
AB  - Phenomenological research in nursing has come under sustained attack in recent
      years with some nurse researchers accused of betraying the fundamental tenets of
      phenomenology and of misconstruing its key concepts. This paper aims to show how
      a study informed by the critique of 'nursing phenomenology' was designed and
      conducted. In particular, the implications of the key phenomenological concepts
      of intentionality and bracketing for data collection, data analysis and the
      presentation of findings are explored in relation to an investigation of the
      concept of the Clinical Placement Coordinator (CPC), an innovative student
      support role in Irish nursing education. The paper shows how an understanding of
      the key phenomenological notions of bracketing and intentionality, and careful
      consideration of their implications for research design and conduct, can enrich
      nursing research by retaining the objectivity and critique central to the
      phenomenological method. The illumination and clarification of contested and
      complex concepts can be achieved by encouraging both researcher and co
      researchers to get 'back to the things themselves' by taking a fresh unprejudiced
      look at the necessary and sufficient elements of phenomena of interest to nursing
      as they appear to those who experience them.

PMID- 15982469
TI  - Parameter characterization of high-overtone bulk acoustic resonators by resonant
      spectrum method.
AB  - Effects of electrode on high-overtone bulk acoustic resonator (HBAR) spectra are
      analyzed by numerical simulation. The figure of merit (FOM), the effective
      electromechanical coupling factor, k(eff)(2)(m), and the quality factor Q(s) of
      the unique mode are discussed based on the resonance spectra of the HBAR. It is
      demonstrated that electrodes with proper acoustic impedance and thickness could
      improve the performance of the HBAR, or degrade the performance if the electrodes
      are not properly chosen.

PMID- 15982468
TI  - Nursing advocacy-a review of the empirical research 1990--2003.
AB  - This paper provides an overview of the empirical research literature on nursing
      advocacy. It offers a description of the contexts, methods and issues of validity
      and reliability used in studies of nursing advocacy, as well as advocacy
      definitions, activities and consequences as results of those studies. The review
      focuses on empirical articles retrieved from the CINAHL and MEDLINE databases
      published between 1990 and 2003. It draws attention to complexity the concept of
      advocacy, difficulties in operationalisation, and concentration on reactive
      advocacy from nurses' perspective. There is a lack of research on patients'
      perspectives of nursing advocacy in general hospital settings.

PMID- 15982470
TI  - Numerical and experimental analysis of strongly nonlinear standing acoustic waves
      in axisymmetric cavities.
AB  - In this paper the behaviour of strongly nonlinear waves in axisymmetric
      resonators is experimentally and numerically studied. Experiments are carried out
      in a cylindrical cavity, which transversal dimension is bigger than the
      longitudinal one, excited by a narrow band transducer. The quality factor and
      displacement amplitudes are experimentally quantified. A finite difference
      numerical model is developed to solve, in the time domain, a proposed set of full
      nonlinear differential equations written in Lagrangian coordinates. Pressure
      field is obtained for complicated modes. Good agreement between numerical and
      experimental results is found. New nonlinear properties of quasi-standing waves
      in axisymmetric resonators are described. Results are compared to linear
      approximation and show the importance of three-dimensional analysis.

PMID- 15982471
TI  - Ultrasonic assessment of tissue hydration status.
AB  - Tissue water content is an important diagnostic parameter that can be used for
      estimation of water loss in muscles such as common dehydration during high
      endurance exercises. It could be also applied for evaluation of the increased
      fluids content in the tissue caused by the variety of pathological conditions or
      edemas. Ultrasonic method for tissue water content monitoring is based on the
      premise that the speed of a bulk or compression sound wave is determined mainly
      by the molecular content of the tissue. Most soft tissues, including muscles that
      consist of about 70-80% water, exhibit shift of the ultrasound velocity
      associated with the change in their water content. In the present paper, we
      tested the feasibility of assessing changes in tissue water content by
      measurements of ultrasound velocity in ex vivo animal muscle tissues. An increase
      in the ultrasound velocity correlated with the volumetric water loss in the
      tissue was observed when other tissue components (proteins, fat) remained
      constant. Possibility to assess muscle dehydration with 1% accuracy was confirmed
      in model dehydration experiments, where ultrasound velocity slope of about 3 m/s
      per 1% of water loss was revealed at measurement error less than 2 m/s. Hence,
      the ultrasonic approach can provide basis for a convenient, lightweight system in
      sports medicine for monitoring total body hydration during long-term endurance
      exercise in hot conditions, as well as for edemas monitoring and other medical
      applications.

PMID- 15982473
TI  - Acoustic radiation force acting on elastic and viscoelastic spherical shells
      placed in a plane standing wave field.
AB  - The theory of the acoustic radiation force acting on elastic spherical shells
      suspended in a plane standing wave field is developed in relation to their
      thickness and the content of their hollow regions. The theory is modified to
      include the effect of a hysteresis type of absorption of compressional and shear
      waves in the material. The fluid-loading effect on the acoustic radiation force
      function Y(st) is analyzed as well. Results of numerical calculations are
      presented for a number of elastic and viscoelastic materials, with the hollow
      region filled with water or air. These results show how the damping due to
      absorption, the change of the interior fluid inside the shells' hollow regions,
      and the exterior fluid surrounding their structures, affect the acoustic
      radiation force.

PMID- 15982472
TI  - Use of multiple acoustic wave modes for assessment of long bones: model study.
AB  - Multiple acoustic wave mode method has been proposed as a new modality in axial
      bone QUS. The new method is based on measurement of ultrasound velocity at
      different ratio of wavelength to the bone thickness, and taking into account both
      bulk and guided waves. It allows assessment of changes in both the material
      properties related to porosity and mineralization as well as the cortical
      thickness influenced by resorption from inner layers, which are equally important
      in diagnostics of osteoporosis and other bone osteopenia. Developed method was
      validated in model studies using a dual-frequency (100 and 500 kHz) ultrasound
      device. Three types of bone phantoms for long bones were developed and tested:
      (1) tubular specimens from polymer materials to model combined changes of
      material stiffness and cortical wall thickness; (2) layered specimens to model
      porosity in compact bone progressing from endosteum towards periosteum; (3)
      animal bone specimens with both cortical and trabecular components. Observed
      changes of the ultrasound velocity of guided waves at 100 kHz followed gradual
      changes in the thickness of the intact cortical layer. On the other hand, the
      bulk velocity at 500 kHz remained nearly constant at the different cortical layer
      thickness but was affected by the material stiffness. Similar trends were
      observed in phantoms and in fragments of animal bones.

PMID- 15982474
TI  - The influence of ultrasonic-vibration on hot upsetting of aluminum alloy.
AB  - The traditional ultrasonic apparatus cannot be operated at high temperature,
      explaining why the effect of ultrasonic-vibration on high temperature metal
      forming has seldom been addressed in literature. This study establishes an
      ultrasonic-vibration hot upsetting system. A cooling mechanism is used to solve
      the problem of high temperature. The effects of temperature and strain rate
      during ultrasonic-vibration on the upsetting of aluminum alloy were explored
      using this new system. Experimental results indicate that ultrasonic-vibration
      can considerably reduces the compressive forces during hot upsetting. The
      reducing effect on compressive forces decreases while the temperature increases.
      The strain rate does not significantly affect the reducing effect on compressive
      forces.

PMID- 15982475
TI  - Mutually induced variations in dissipation and elasticity for oscillations in
      hysteretic materials: non-simplex interaction regimes.
AB  - Self-action and effects mutually induced by oscillations interacting in
      hysteretic media are investigated analytically and numerically. Special attention
      is paid to non-simplex processes for which presence of intermediate extrema
      results in appearance of minor nested loops inside the main hysteretic stress
      strain loop. Non-simplex regimes are typical of interaction of excitations having
      different frequencies and amplitudes, but comparable strain rates. It is found
      that, due to transition between the regimes, frequency and amplitude dependencies
      of the variations in elasticity and dissipation induced by one wave for another
      one may become non-monotonous. Either additional dissipation or induced
      transparency may occur in different regimes. The results obtained are important
      for correct interpretation of experimental data on nonlinear acoustic
      interactions in rocks and many other microstructured (mesoscopic) solids that are
      known to exhibit elastic hysteresis and memory properties.

PMID- 15982476
TI  - Glycan moiety modifications of feline alpha1-acid glycoprotein in retrovirus
      (FIV, FeLV) affected cats.
AB  - alpha1-Acid glycoprotein (AGP) is considered one of the major acute phase
      proteins in cats. In humans, AGP is a heavily glycosylated protein that undergoes
      several modifications of its glycan moiety during acute and chronic inflammatory
      pathologies. In this paper we present the feline AGPs (fAGP) glycan moiety
      modifications in the course of two prevalent feline diseases, the FIV (feline
      immunodeficiency virus) dependent feline acquired viral immunodeficiency and the
      feline leukemia virus (FeLV) associated lymphoma. The glycan moiety of fAGP was
      investigated by means of the binding of its oligosaccharides residues with
      specific lectins. Four lectins were used: Sambucus nigra agglutinin I and Maackia
      amurensis agglutinin lectins were used to detect sialic acid residues, Aleuria
      aurantia lectin was used to detect L-fucose residues and Concanavalin A was used
      to evaluate the degree of branching. It was found that fAGP undergoes several
      post-translational modifications of its glycan pattern: in particular the degree
      of sialylation is increased in FeLV-positive cats diagnosed with lymphoma, while
      FeLV-positive that did not presented any specific clinical signs cats do not
      present any increase of expression of sialic acid on the surface. Furthermore,
      FIV induced a modification of the glycan moiety of fAGP, which however varied
      widely among individuals. In order to determine the number and the position of
      oligosaccharide chains, the cDNA sequence of fAGP was also determined. The
      translation of the mature fAGP coding sequence gave rise to a sequence of 183
      residues, with five potential N-glycosylation sites, but also with seven
      potential phosphorylation sites.

PMID- 15982477
TI  - Production of antibodies to canine IL-1beta and canine TNF to assess the role of
      proinflammatory cytokines.
AB  - IL-1 and TNF are important proinflammatory cytokines implicated in both
      antimicrobial host defense and pathogenesis of diseases with an immune-mediated
      and/or inflammatory component. Respective studies in the dog have been hampered
      by the unavailability of reagents allowing the specific measurement of canine
      cytokine proteins and the effect of canine cytokine neutralization by Ab.
      Starting with recombinant canine (rcan) IL-1beta and rcanTNF, four polyclonal
      antisera and 22 mAb specific for rcanIL-1beta and rcanTNF were generated. Their
      usefulness in neutralization assays was determined. Using cytokine-containing
      supernatants of canine cells in bioassays, polyclonal antisera neutralized either
      canine IL-1beta or TNF. TNF was also neutralized by three antibodies developed in
      this study and one commercial mAb. The usefulness of monoclonal and polyclonal Ab
      in canine cytokine-specific Ab capture ELISA's was assessed. This resulted in the
      identification of a commercial mAb combination and one pair developed in this
      study allowing low levels of TNF to be detected by antibody capture ELISA. The
      detection limit was 141 pg/ml rcanTNF for both combinations. Using rcanIL-1beta
      as an antigen allowed the detection of lower concentrations of rcanIL-1beta (20
      pg/ml, on the average) by a pair of polyclonal antisera than when monoclonals
      were used. By using such IL-1beta-specific and TNF-specific ELISA's, the
      respective cytokines were detected in supernatants of canine PBMC stimulated with
      LPS or heat-killed Listeria monocytogenes and interferon-gamma combined. Thus,
      monoclonal and polyclonal reagents were identified allowing the quantitation of
      canine IL-1beta and TNF production in vitro, and the neutralization of these
      cytokines.

PMID- 15982478
TI  - Production of eosinophil chemoattractant activity by ovine gastrointestinal
      nematodes.
AB  - Eosinophilia is a well documented feature of helminth infections but the precise
      nature of the interaction between parasite and eosinophil remains an enigma. This
      paper describes experiments demonstrating that ruminant gastrointestinal
      trichostrongyles produce potent chemoattractant activity for ovine bone marrow
      derived eosinophils in vitro. This activity was initially identified as a
      constituent of whole worm extracts of third and fourth larval (L3, L4), and adult
      stages of Teladorsagia circumcincta, and adult Haemonchus contortus. Similar
      activity was detected in excretory/secretory (E/S) material derived from live T.
      circumcincta L3. Subsequently, by adapting the assay technique to incorporate
      live worms directly into the system, it was shown that L3 of both T. circumcincta
      and H. contortus produced eosinophil chemoattractant activity. In contrast,
      neither whole worm extracts, or E/S preparations from mixed stages of the free
      living nematode Caenorhabditis elegans contained eosinophil chemoattractant
      activity, and there was no evidence of chemoattractant production by live C.
      elegans. The results described are challenging to the traditional dogma that
      eosinophils are host-protective effector cells, and raise the intriguing
      possibility that ovine nematodes actively encourage recruitment of eosinophils.
      Local eosinophil-mediated mucosal damage, comparable to that seen in the
      asthmatic lung, may then provide a permissive local microenvironment for the
      parasite. Moreover, if they prove important for pathogenicity, nematode
      chemoattractants could offer future potential as novel therapeutic targets.

PMID- 15982479
TI  - Mouse models of osteoarthritis provide new research tools.
AB  - The options for pharmaceutical intervention of osteoarthritis are limited. There
      is therefore a crucial need for animal models of osteoarthritis that can be used
      as research tools for improving our understanding of the disease and for
      discovering and testing new treatments. Recently, a new mouse model of
      osteoarthritis was described in which the mice are unable to produce a bone
      morphogenetic protein (BMP) receptor specifically in joints. A comparison of this
      model to other models with different etiologies is presented. The findings
      suggest that all of the models could be linked molecularly.

PMID- 15982480
TI  - The darker side of Ca2+ signaling by neuronal Ca2+-sensor proteins: from
      Alzheimer's disease to cancer.
AB  - Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF
      hand Ca2+-binding proteins that are expressed mainly in neurons or retinal
      photoreceptor cells. A variety of different neuronal functions have been
      attributed to these proteins. However, important new discoveries indicate that
      these proteins also have key roles in pathological processes of disease. Thus, a
      'darker side' of NCS protein signaling has become evident in some CNS disorders,
      such as Alzheimer's disease and schizophrenia, and in cancer. In this article, I
      will provide an overview of the current, and rapidly expanding, knowledge of how
      this important family of proteins might be involved in various major CNS
      diseases, the proposed role of NCS proteins in pathophysiological signaling and
      the development of pharmacological tools and novel research strategies.

PMID- 15982481
TI  - Improved estimation of GFR by serum cystatin C in patients undergoing cardiac
      catheterization.
AB  - Clinical assessment of glomerular filtration rate (GFR) mainly relies on single
      determinations of serum creatinine (crea) which is commonly insensitive to mild
      renal dysfunction. Serum cystatin C (cysC) has been proposed as an alternative
      endogenous marker of GFR showing higher correlation to standard clearance methods
      such as inulin or iohexol clearance. We compared serum crea and cysC levels in
      n=127 patients undergoing cardiac catheterization. The clearance of the iodinated
      contrast dye iopromide served as reference method for GFR. Serum cysC was
      determined by a particle-enhanced immunonephelometric method. CysC showed higher
      non-parametric correlation (r=0.805) to the iopromide clearance compared to crea
      (r=0.652) and to the estimated GFR according to the Cockcroft-Gault formula
      (r=0.690), which underestimated true GFR systematically. Receiver operating
      curves revealed a greater area-under-the-curve (AUC) for cysC (0.957 vs. 0.801,
      p<0.05). At a cut-off level of >1.3 mg/l cysC exhibited an 88% sensitivity and a
      96% specificity for detecting renal dysfunction which was defined as an iopromide
      clearance less than 80 ml/min/1.73 m2; best values for crea were 63% for
      sensitivity and 80% for specificity at a cut-off of >1.2 mg/dl. In conclusion,
      cysC detected reduced GFR more reliably and at an earlier stage in patients
      undergoing cardiac catheterization allowing a better identification of patients
      with renal dysfunction and those at risk for contrast damage.

PMID- 15982482
TI  - Comparison of angiographic and clinical outcomes between rotational atherectomy
      versus balloon angioplasty followed by radiation therapy with a rhenium-188
      mercaptoacetyltriglycine-filled balloon in the treatment of diffuse in-stent
      restenosis.
AB  - BACKGROUND: The purpose of this study was to compare the efficacy of rotational
      atherectomy (RA) with simple balloon angioplasty, prior to beta-radiation therapy
      with a rhenium-188-mercaptoacetyltriglycine (188Re-MAG3)-filled balloon for
      diffuse in-stent restenosis (ISR). METHODS: After completing 50 cases with RA
      prior to beta-radiation (Group I), we performed optimal balloon angioplasty
      followed by beta-radiation in the next 53 consecutive patients (Group II) for the
      treatment of diffuse ISR. The radiation dose was 15 Gy at a depth of 1.0 mm into
      the vessel wall. RESULTS: The baseline clinical and angiographic characteristics
      were similar between the two groups. The mean length of the lesion was 25.6+/
      12.7 mm in Group I and 22.9+/-8.6 mm in Group II (p=0.26). Radiation was
      successfully delivered to all patients, with a mean irradiation time of 179+/-55
      s. The 6-month angiographic restenosis rate was 10% (5/50) in Group I versus 33%
      (17/51) in Group II (p=0.007). No adverse event including myocardial infarction,
      death, or stent thrombosis occurred during the 1-year follow-up period. The risk
      of a target lesion revascularization or a major adverse cardiac event was
      significantly lower in Group I than in Group II (two patients in Group I vs. nine
      patients in Group II; OR, 0.20; 95% CI, 0.04-0.96; p=0.04). CONCLUSION:
      Concomitant treatment with rotational atherectomy and beta-irradiation using a
      188Re-MAG3-filled balloon for diffuse ISR has a synergistic effect, in terms of 6
      month angiographic restenosis and 1-year cardiac event-free survival.

PMID- 15982483
TI  - Release of endothelin-1 from human endocardium after radiofrequency catheter
      ablation and coronary angioplasty: comparative results.
AB  - BACKGROUND: Plasma levels of endothelin-1 (ET-1) increase after coronary
      angioplasty (PTCA) due to endothelial injury during the procedure. ET-1 has been
      found in human endocardial and myocardial cells. It is not known whether ET-1
      increases after thermal injury induced by radiofrequency catheter ablation (RFA).
      METHODS: We determined plasma ET-1 levels at baseline, immediately after, and at
      2 and 6 h post-procedure in 31 patients undergoing PTCA and 16 patients
      undergoing RFA. Patients subjected to diagnostic coronary angiography (n=15) or
      electrophysiology study (n=13) served as controls. RESULTS: Compared to baseline,
      ET-1 levels increased significantly immediately post-PTCA (55.1+/-20.1 vs. 42.7+/
      14.9 pg/ml, p<0.01) and at 2 h post-RFA (98.0+/-11.7 vs. 53.0+/-17.4 pg/ml,
      p<0.01) and returned to baseline measurements at 2 h post-PTCA and 6 h post-RFA.
      There was no change of ET-1 levels in the control groups. ET-1 kinetics curve was
      significantly higher post-RFA compared to post-PTCA (p<0.001). ET-1 immediately
      post-PTCA correlated with total pressure-time product applied for balloon
      inflation during the procedure (r=0.56, p<0.01). There was no correlation between
      ET-1 levels and the number of RFA applications. No patient developed ischemia
      post-PTCA. There were no complications or arrhythmia recurrences post-RFA.
      CONCLUSION: Endocardial thermal injury incurred during RFA is another mechanism
      of endothelin increase apart from mechanical injury of the coronary endothelium
      during PTCA and represents further evidence for the existence of the peptide in
      human endocardial endothelial and myocardial cells. ET-1 increase is delayed and
      more pronounced post-RFA compared to post-PTCA. Despite that, it does not seem to
      have any clinical impact in the immediate post-RFA period.

PMID- 15982484
TI  - Preliminary experience in the assessment of aortic valve calcification by ECG
      gated multislice spiral computed tomography.
AB  - BACKGROUND: The aim was to correlate the degree of valvular calcification in
      patients with aortic stenosis determined by retrospectively electrocardiogram
      (ECG)-gated multislice spiral computed tomography with stenosis severity assessed
      by cardiac catheterization. METHODS: Prospective study on 41 patients (18 men,
      mean age 71+/-8 years) with aortic stenosis, who underwent four detector row
      multislice spiral computed tomography and cardiac catheterization. Severity of
      aortic stenosis was classified by cardiac catheterization. Aortic valve area,
      peak to peak and mean transvalvular gradients were correlated with the degree of
      calcification determined by multislice spiral computed tomography. Aortic valve
      calcification was assessed using aortic Agatston score, aortic mass score and
      aortic volume score. RESULTS: All measured aortic valve calcification scores were
      significantly higher in patients with severe aortic stenosis (n=29) than in
      patients with moderate (n=7) or mild aortic stenosis (n=5, p<0.001). Aortic valve
      calcification scores correlated significantly with aortic valve area (r=-0.49,
      p=0.001 for aortic mass score) and with peak to peak (r=0.68, p<0.001) and mean
      (r=0.60, p<0.001) transvalvular gradients. CONCLUSIONS: Severity of aortic valve
      calcification assessed by cardiac multislice spiral computed tomography is
      inversely related to aortic valve area and positively correlated with
      transvalvular gradients. Based on this preliminary data larger studies should be
      performed with echocardiography as a reference standard in order to validate this
      new information and its utility in the clinical management of the patient.

PMID- 15982485
TI  - Cumulative incidence of coronary lesions with vulnerable characteristics in
      patients with stable angina pectoris: an intravascular ultrasound and
      angiographic study.
AB  - BACKGROUND: Development of vulnerable lesion may take place simultaneously at
      many sites of coronary vasculature, therefore causing multisite instability. The
      prevalence of the phenomenon in stable angina (SA) patients remains unknown. The
      aim of our study was to assess, in patients with stable angina, the prevalence of
      coronary plaques with vulnerable characteristics and to ascertain whether the
      number of such lesions may accumulate. METHODS: Vulnerable plaques are
      characterised by positive remodelling on intravascular ultrasound (IVUS) and with
      complex appearance on angiography. We performed preprocedural IVUS in target
      lesion of 67 patients with SA (46 males, age 55.9). Remodelling index (RI)
      defined as vessel area at the target lesion divided by that of average reference
      segments > or = 1.05 was assumed as positive remodelling. Plaques of > or = 30%
      stenosis on angiography were classified into complex or smooth groups. RESULTS:
      Positive remodelling was found in 30 (44.8%) and complex plaque in 16 (23.9%) of
      67 target lesions. Multiple complex plaques were present in 21 (31.3%) patients.
      Plaques with positive remodelling more often were complex on angiography (12/30
      vs. 4/37, respectively; p=0.005) and were more often associated by complex
      plaques at other sites (35/30 vs. 23/37; p=0.04) than the remaining lesions.
      Moreover, the presence of positive remodelling predicted multiple complex lesions
      at other sites (OR 5.6; 95% CI 1.7-18.3). CONCLUSION: Multiple coronary plaques
      with vulnerable characteristics are present in nearly one third of patients with
      stable angina. Incidence of vulnerable lesions may have cumulative character,
      i.e. the presence of one vulnerable lesion predicts occurrence of further
      vulnerable plaques.

PMID- 15982486
TI  - Echocardiographic assessment of left ventricular morphology and function in
      patients with Emery-Dreifuss muscular dystrophy.
AB  - BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) characterized by
      musculoskeletal abnormalities is often associated with atrioventricular
      conduction disturbances. Although some EDMD patients were reported to develop
      dilated cardiomyopathy, there are limited data on their left ventricular (LV)
      performance. METHODS: Therefore, we echocardiographically assessed 27 men (23
      cases aged 26.4+/-6.8 years with X-linked, and four cases aged 22.2+/-8.6 years
      with autosomal dominant (AD)) EDMD. Control group included 16 male healthy
      controls aged 24.8+/-6.0 (18-37) years. RESULTS: Although LV end diastolic
      dimension was similar in EDMD and controls (4.9+/-0.6 and 4.99+/-1.1 cm, ns),
      dilated left ventricle was found in three X-linked EDMD subjects. LV ejection
      fraction was significantly reduced in EDMD (62.3+/-1% vs. 71.2+/-2%, p=0.01) and
      was below 50% in six (22.2%) X-linked EDMD patients. Doppler analysis disclosed
      prolonged isovolumetric relaxation time of the left ventricle in the studied
      group. This finding may indicate impaired LV relaxation. CONCLUSION: A
      significant subgroup of X-linked EDMD patients shows pronounced abnormalities of
      left ventricular function. This warrants cardiologic follow up of EDMD patients.

PMID- 15982487
TI  - Weekly electrocardiographic pattern in mice infected with two different
      Trypanosoma cruzi strains.
AB  - BACKGROUND: Chagas' disease, which is caused by Trypanosoma cruzi, affects 20
      million people. The electrocardiographic alterations are usually the first
      evidence of disease progression. In this work, we evaluated if two different T.
      cruzi strains presented electrocardiographic and heart histopathological
      alterations that could be characteristic and only achieved to the parasite
      strain. The moment when the electric alterations began was also studied. METHODS:
      Albino mice (n=100) were inoculated with 50 (n=50) and 500 (n=50) trypomastigotes
      of T. cruzi, for Tulahuen strain and SGO-Z12 isolate, respectively.
      Electrocardiograms were obtained before infection and once a week from 7 to 147
      days post infection (d.p.i). Dipolar and unipolar leads were analyzed. Hearts
      were removed by necropsy on 14, 90 and 147 d.p.i. Each heart was cut horizontally
      into 5-mum sections and they were stained with Hematoxilin-Eosine. RESULTS: At
      147 d.p.i., 30% of Tul-infected mice were found alive, while in the SGO-Z12
      infected group, 75% were alive at the same moment. The Tul-infected group showed
      more intraventricular blockage alterations than the other groups from 49 to 70
      d.p.i, (p<0.01). No structural cardiac alterations were detected in SGO-Z12
      infected mice at 7 d.p.i., while the Tul-infected group showed mononuclear cell
      infiltrates. At 147 d.p.i., fiber disorganization and cell infiltration were
      observed in the SGO-Z12 and Tul-infected groups. CONCLUSIONS: We demonstrated
      that T. cruzi Tulahuen strain and SGO-Z12 isolate determined different
      electrocardiographic alterations which were characteristic for each stage of the
      experimental Chagas' disease. These results highlight the importance of the T.
      cruzi strain in the severity of the cardiopathy.

PMID- 15982488
TI  - Autonomic modulation of the sinus node following electrical cardioversion of
      persistent atrial fibrillation: relation with early recurrence.
AB  - BACKGROUND: The aim of this study was to correlate early atrial fibrillation (AF)
      relapses with heart rate variability (HRV) parameters immediately recorded after
      electrical cardioversion (EC) of persistent AF. METHODS AND RESULTS: We performed
      the spectral analysis of short-term HRV 30 min after EC in 25 patients with
      persistent AF. The numbers of patients who maintained sinus rhythm at 48 h, 7,
      and 30 days were 22, 16, and 14, respectively. A very low low frequency/high
      frequency ratio (0.93+/-0.08 vs. 1.89+/-1.30; p<0.003) significantly identified
      patients with AF recurrence at 48 h in comparison to patients without AF
      recurrence. On the contrary, HRV parameters did not identify patients with AF
      recurrence at 7 or 30 days. CONCLUSIONS: AF relapsed within the first 48 h more
      frequently in patients who presented a predominant vagal tone immediately after
      the restoration of sinus rhythm.

PMID- 15982489
TI  - Usefulness of strain rate imaging in detecting ischemic myocardium during
      dobutamine stress.
AB  - BACKGROUND: Tissue Doppler imaging-derived systolic myocardial velocity can
      detect subtle alterations in contractility during dobutamine stress. However,
      increased cardiac translation and tethering during dobutamine stress may affect
      measurements. METHODS: To examine the hypothesis that regional ischemic
      myocardium can be sensitively detected during dobutamine stress using myocardial
      strain rate, a new indicator of regional myocardial contraction that is
      independent of cardiac translation and tethering, we studied seven closed-chest
      pig confirmed chronic ischemic models produced by placing an ameroid constrictor
      on the left circumflex artery. Left ventricular short-axis tissue Doppler imaging
      was obtained at baseline and during dobutamine stress (10 and 30 microg/kg/min).
      Peak systolic myocardial velocity and peak systolic myocardial strain rate in
      anterior and posterior segments were derived offline at each stage. RESULTS: In
      peak systolic myocardial velocity and peak systolic myocardial strain rate,
      repeated-measures analysis of variance showed significant interaction between
      nonischemic and ischemic segments during dobutamine stress. Statistical
      significance between nonischemic and ischemic segments was reached at baseline,
      10 microg/kg/min dobutamine, and 30 microg/kg/min dobutamine in peak systolic
      myocardial strain rate, and at 30 microg/kg/min dobutamine in peak systolic
      myocardial velocity. By receiver operating characteristic (ROC) analysis for
      predicting ischemic segments at 30 microg/kg/min dobutamine, a cutoff value of
      peak systolic myocardial strain rate was 4.84, with a sensitivity of 100% and a
      specificity of 100%. Peak systolic myocardial velocity was the less
      discriminating parameter (cutoff, 6.46; sensitivity, 86%; specificity, 86%).
      CONCLUSIONS: Myocardial strain rate imaging might represent an accurate parameter
      for clinical recognition of regional ischemic myocardium during dobutamine stress
      echocardiography.

PMID- 15982490
TI  - Gene expression profiling of human atrial myocardium with atrial fibrillation by
      DNA microarray analysis.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered
      arrhythmia in the clinical setting. However, a comprehensive investigation of the
      molecular mechanism of AF has not been performed. The aim of this study was to
      clarify transcriptional profiling of genes modulated in the atrium of AF patients
      using DNA microarray technology. METHODS: We obtained 17 fresh cardiac specimens,
      right atrial appendages, isolated from 10 patients with normal sinus rhythm and
      seven chronic AF patients who underwent cardiac surgery. Affymetrix GeneChip
      (Human Genome U95A) investigating 12,000 human genes was used for each specimen.
      Quantitative analysis of selected genes was performed by the real-time PCR
      method. RESULTS: The left atrial diameter in the AF group was greater than that
      in the sinus rhythm group. We could identify 33 AF-specific genes that were
      significantly activated (>1.5-fold), compared with the sinus rhythm group,
      including an ion channel, an antioxidant, an inflammation, three cell growth/cell
      cycle, three transcription such as nuclear factor-interleukin 6-beta, several
      cell signaling and several protein genes, and seven expressed sequence tags
      (ESTs). In contrast, we found 63 sinus rhythm-specific genes, including several
      cell signaling/communication such as sarcoplasmic reticulum Ca2+-ATPase 2,
      several cellular respiration and energy production and two antiproliferative or
      negative regulator of cell growth genes, and 22 ESTs. CONCLUSIONS: The present
      study demonstrated that about one hundred genes were modulated in the atria of AF
      patients. These findings suggest that these genes may play critical roles in the
      initiation or perpetuation of AF and the pathophysiology of atrial remodeling.

PMID- 15982491
TI  - Risk stratification in a Brazilian hospital-based cohort of 1220 outpatients with
      heart failure: role of Chagas' heart disease.
AB  - BACKGROUND: Few studies evaluated prognostic factors of outpatients with heart
      failure of different etiologies including Chagas' heart disease. METHODS: We
      studied 1220 outpatients with heart failure in functional classes III and IV
      (NYHA) to evaluate prognostic factors. Patients aged 13-72 years (mean 45.5,
      standard deviation 11); 952 men (78%) and 268 women (22%) were followed up for
      25.6+/-26 months from 1991 to 2000. Heart failure was attributed to idiopathic
      dilated cardiomyopathy in 454 (37%) patients. Etiologies were Chagas' heart
      disease in 242 (20%) patients, ischemic cardiomyopathy in 212 (17%), hypertensive
      cardiomyopathy in 170 (14%) and others in 142 (12%). Statistical analyses were
      performed with Kaplan-Meier and Cox proportional hazards methods, following a
      strategy of noninvasive model as well as in an invasive model to identify the
      risk of death. RESULTS: Four hundred fifteen (34%) patients died in the follow-up
      period, 71 (6%) patients underwent heart transplantation and 28 (2%) underwent
      other surgical interventions. In the noninvasive model, Chagas' heart disease
      (relative risk compared with other etiologies 2.26 to 2.97), left ventricular end
      diastolic diameter on echocardiography (relative risk 1.13) and left ventricular
      ejection fraction on radionuclide angiography (relative risk 0.96) were
      associated with higher mortality. In the invasive model, Chagas' heart disease
      (relative risk compared with other etiologies 2.66 to 9.13) was the most
      important determinant of mortality in association with the cardiac index
      (relative risk 0.40). CONCLUSIONS: In this cohort of patients with heart failure
      of different etiologies, Chagas' heart disease was the main prognostic factor for
      mortality.

PMID- 15982492
TI  - Thrombolytic therapy use for acute myocardial infarction and outcome in Qatar.
AB  - OBJECTIVE: Data on the outcome of patients treated with thrombolytic therapy in
      the Arab world is scarce. The main objective of this study is to study the 7-day
      morbidity and mortality rate and the rate of use of thrombolytic therapy in
      patients presenting with acute myocardial infarction treated with thrombolytic
      therapy in the Middle East. METHODS: We conducted a retrospective analysis of
      prospectively collected data for all patients who were admitted to Coronary Care
      Unit in Cardiology Department in Hamad Medical during the period (1991-2001).
      Patients were divided into two groups in relation to ethnicity whether they
      received thrombolysis or not. In each group, the number of patients, age at the
      time of admission, gender, cardiovascular risk profile, therapy and outcome in
      regard of in-hospital complication and 7-day death as primary end point were
      analyzed. RESULTS: Of the total 5388 patients admitted with acute myocardial
      infarction during the 10-year period, 66.3% (3567) with STE MI were found, 61.4%
      (2190) of them received thrombolytic therapy while 38.6% (1377) were not eligible
      for thrombolytic therapy. The remaining 33.7% (1821) were admitted with non-STE
      MI. In consideration of ethnic variation, patients with STE MI eligible for
      thrombolytic therapy, 29.6% (1598) were Qataris and 70.4% (3792) were non
      Qataris. Thrombolytic therapy was administered to 25.9% (414) of Qatari patients
      and 51.3% (1947) of non-Qataris. The mortality rate of Qatari patients who
      received thrombolytic therapy was 9.2% (38) vs. 19.5% (231) who did not receive
      thrombolytic therapy (p<0.001). In non-Qatari patients, the mortality rate was
      5.2% (102) for those who received thrombolytic therapy, while it was 8.6% (159)
      for those with no thrombolytic therapy (p<0.001). When compared to male patients,
      female patients with thrombolytic therapy had higher mortality rates (in both
      Qataris and non-Qataris) (20.5% vs. 6.1%; p value<0.001 and 16.1% vs. 9.4%;
      p<0.001, respectively), there were no significant differences between the ethnic
      groups in regard to in-hospital complications. Patients treated with thrombolytic
      therapy had lower incidence of in-hospital complication regarding acute heart
      failure, post-myocardial angina, heart block and arrhythmia. Thrombolytic therapy
      reduced mortality rate in acute myocardial infarction by 69%. Logistic regression
      analysis had shown that arrhythmia, acute heart failure, heart block, cardiogenic
      shock, diabetes mellitus and stroke were independent predictors of increased
      mortality. Thrombolysis was used in 61.4%, which is still underutilized when
      compared to a few available studies in the Gulf area, and to other studies in the
      developed world. CONCLUSION: In the current study, use of thrombolysis in acute
      myocardial infarction was associated with significant decrease in in-hospital
      mortality and morbidity. Mortality rate was higher in the Qatari nationals when
      compared to non-Qataris. Reperfusion therapy may be underutilized in the
      developing world. Increased use of reperfusion therapy would result in reduced
      mortality rate. Global measures to encourage the use of reperfusion therapy
      including patients' education, and strategies to improve the health care system
      are needed.

PMID- 15982493
TI  - The beneficial effect of insulin, glucose, and dipyridamole on regional left
      ventricular function early after acute myocardial infarction.
AB  - BACKGROUND: High-dose glucose-insulin-potassium (GIK) solution has beneficial
      effects on reducing mortality in acute myocardial infarction. Dipyridamole (DIP)
      is a powerful antioxidant and increases adenosine concentration. Experimentally,
      GIK and DIP have additive protective effects in ischemia-reperfusion injury. AIM:
      This work aims to assess the acute effects of DIP alone, GIK alone, and GIK+DIP
      on left ventricular function in patients evaluated early after an acute
      myocardial infarction. METHODS: Ten male patients (age 63+/-11 years) with
      uncomplicated acute myocardial infarction were evaluated within 3 days after
      admission. All had been treated with systemic thrombolysis and were on full
      therapy (including beta-blockers) at the time of testing. They underwent stress
      echocardiography [2D echo, with wall motion score index (WMSI) evaluated in a 16
      segment model of the left ventricle, with each segment scored from 1=normal to
      4=dyskinetic] during low-dose DIP alone (0.28 mg/kg in 4 min); GIK alone (4-h
      infusion of glucose 30%, 25 insulin units, and 40 mEq of KCl, at an infusion rate
      of 1.5 ml/kg/h); and GIK+DIP. RESULTS: Regional systolic function (baseline
      WMSI=1.69+/-0.2) improved after DIP (1.54+/-0.1), GIK (1.54+/-0.1), and, to a
      greater extent, after GIK+DIP (1.33+/-0.2; p<0.001 vs. baseline; p<0.05 vs. DIP;
      p<0.05 vs. GIK). CONCLUSION: High-dose GIK has an acute beneficial effect on
      regional left ventricular function in patients with acute myocardial infarction.
      This beneficial effect is potentiated by low-dose DIP coadministration.

PMID- 15982494
TI  - Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated
      backscatter.
AB  - BACKGROUND: It is not known whether cardiac markers and cyclic variations of
      integrated backscatter can be used to detect cardiac sarcoidosis. METHODS: We
      studied 62 patients with sarcoidosis affecting the lung, eyes, skin, or heart (27
      patients with cardiac involvement and 35 patients without). The cyclic variation
      of integrated backscatter and wall thickening was evaluated in the left
      ventricular anterior septum and posterior wall. Plasma A-type natriuretic peptide
      (ANP) and B-type natriuretic peptide (BNP) concentrations and serum cardiac
      troponin T were also determined. RESULTS: Plasma natriuretic peptide
      concentrations were higher in the cardiac involvement group (ANP: 15.5
      [interquartile range (IQR) 2.5-34.0] vs. 12.0 [10.0-16.5] pg/ml, P=0.25; BNP:
      28.6 [5.9-141] vs. 10.1 [4.8-15.4] pg/ml, P=0.049). However, cardiac troponin T
      concentration was <0.01 ng/ml in all patients. Receiver-operator characteristic
      (ROC) analysis showed that both ANP and BNP could identify patients with high
      degree atrioventricular block, ventricular tachyarrhythmias, or symptomatic heart
      failure (the areas under the ROC curve were 0.94 and 0.97, respectively). The
      cardiac involvement group could be distinguished from the noninvolvement group by
      combining cutoff values for the magnitude of integrated backscatter cyclic
      variation (5.5 dB) and wall thickening (30%), albeit only for the posterior wall.
      CONCLUSION: Both ANP and BNP are useful markers for identifying patients with
      sarcoidosis and cardiac complication(s). Moreover, evaluation of integrated
      backscatter cyclic variation combined with wall thickening may be of help in
      detecting cardiac involvement in the posterior wall.

PMID- 15982495
TI  - Association between C1019T polymorphism of connexin37 and acute myocardial
      infarction: a study in patients from Sicily.
AB  - During atherogenesis, a critical role is played by intercellular communication
      via gap junctions, cell membrane channels linking the cytoplasmic compartments of
      adjacent cells. The component protein subunits of these channels, called connexin
      (Cx), belong to a multigene family. Cx37 is involved in growth, regeneration
      after injury and ageing of the endothelial cells, suggesting its role in
      atherosclerosis. The C1019 single nucleotide polymorphism (SNP) of Cx37 gene was
      associated with thickening of the carotid intima in Swedish men and was also
      associated with coronary artery disease in a Taiwanese population. On the other
      hand, in two more recent studies performed in male Japanese population, T1019
      Cx37 SNP has shown to be a risk factor for acute myocardial infarction (AMI). In
      the light of these discrepant results, we have studied the frequency of this SNP
      in a very homogeneous cohort of young male people affected by AMI. We analysed 97
      male Sicilian patients (mean age 40, age range 20-46) and 196 healthy male
      controls (mean age 39, age range 20-55) for C1019T of the Cx37. The 1019T SNP was
      significantly increased in the patients compared to the controls (43.8% vs.
      34.4%; p=0.03 by chi2 test with Yates' correction; odds ratio (OR) 1.5, (1.0-2.1)
      95% confidence interval (CI)). The present case control study performed in a
      homogeneous Caucasoid population confirms the Japanese results that T SNP of Cx37
      gene is involved in AMI phenotype, demonstrating the consistency of the
      association across past studies and across different populations. The differences
      between patients and controls are significant but relatively small with an odd
      ratio risk of 1.5. However, as AMI is a multifactorial disease, any single
      mutation will only provide a small or modest contribution to risk, also depending
      on interaction with other genes and/or a particular environment.

PMID- 15982496
TI  - PRKAR1A gene mutation in patients with cardiac myxoma.
AB  - BACKGROUND: PRKAR1A gene encodes the type 1A regulatory subunit of protein kinase
      A. The mutation of this gene causes Carney complex which is an autosomal dominant
      multiple neoplasia syndrome characterized by spotty pigmentations, endocrine
      overactivity and cardiac myxoma. We hypothesized that cardiac myxoma may be
      associated with PRKAR1A gene mutation and determined whether mutation in the
      PRKAR1A gene is the cause of familial and sporadic cardiac myxoma. METHODS: We
      studied seven patients (three males and four females) with cardiac myxoma. Two of
      them had familial cardiac myxoma complicated with Carney complex. The other five
      patients were characterized as sporadic cardiac myxomas. We analyzed the PRKAR1A
      gene of all patients by the polymerase chain reaction (PCR)-single-strand
      conformation method, followed with direct sequence analysis. RESULTS: We
      identified a novel mutation (494delTG) in exon 4A of the PRKAR1A gene in the
      patients with Carney complex. A 16-year-old proband had a left atrial myxoma,
      pituitary adenoma and skin pigmentation. His father also had left atrial myxoma
      and skin pigmentation. In contrast, no mutations in the PRKAR1A gene were
      identified in the other five patients with sporadic cardiac myxomas. CONCLUSIONS:
      These results suggest that mutation of the PRKAR1A gene may be associated with
      familial cardiac myxoma in Carney complex but may not be associated with sporadic
      cardiac myxoma.

PMID- 15982497
TI  - Complementary roles of simple variables, NYHA and N-BNP, in indicating aerobic
      capacity and severity of heart failure.
AB  - AIMS: The extent of exercise intolerance in patients with chronic heart failure
      (CHF) is dependent on and representative of the severity of heart failure.
      However, few primary care physicians have direct access to facilities for formal
      exercise testing. We have therefore explored whether information readily
      obtainable in the community can reliably predict the functional capacity of
      patients. METHODS AND RESULTS: Ninety-six subjects with a wide range of cardiac
      function (10 healthy controls and 86 CHF patients with NYHA classes I-IV, LVEF
      36.9+/-15.2%) were recruited into the study and had resting plasma N-BNP and
      cardiopulmonary exercise testing to measure peak oxygen consumption (VO2).
      Significantly higher N-BNP levels were found in the CHF group (299.3 [704.8]
      fmol/ml, median [IQR]) compared with the healthy control group (7.2 [51.2]
      fmol/ml), p<0.0001. There were significant correlations between peak VO2 and N
      BNP levels (R=0.64, P<0.001), peak VO2 and NYHA class (R=0.76, P=0.001), but no
      significant correlation was seen between peak VO2 and LVEF (R=0.0788, P=0.33).
      Multivariate analysis identified plasma N-BNP (P<0.0001) and NYHA class
      (P<0.0001) as significant independent predictors of peak VO2. Logistic modelling
      with NYHA class and log N-BNP to predict peak VO2<20 ml/kg/min showed that the
      area under the curve of receiver-operating-characteristic (ROC) curve was 0.906
      (95% CI 0.844-0.968). A nomogram based on the data has been constructed to allow
      clinicians to estimate the likelihood of peak VO2 to be <20 ml/kg/min for given
      values of plasma N-BNP and NYHA class. CONCLUSIONS: By combining information from
      a simple objective blood test (N-BNP) and a simple scoring of functional status
      (NYHA), a clinician can deduce the aerobic exercise capacity and indirectly the
      extent of cardiac dysfunction of patients with CHF.

PMID- 15982499
TI  - Congenital heart disease in a population of dizygotic twins: an echocardiographic
      study.
AB  - BACKGROUND: Congenital heart disease (CHD) is the most common malformation in the
      fetal and neonatal period but little is known about its cause. The distribution
      analysis of CHD in dizygotic twins could provide a useful tool to evaluate the
      role of genetic and environmental factors in the development of CHD. Dizygotic
      twins are siblings with different genes, growing together in the same womb. AIM
      OF STUDY: To investigate the occurrence of CHD in a large sample of dizygotic
      twins of nonconsanguineous healthy parents, comparing the data from non-twin
      patients. METHODS: From January 1999 to December 2002, we enrolled 1743 CHD
      patients with, at least 1 sibling, and 66 pairs of dizygotic twins, referred to
      our tertiary center. The diagnosis of CHD was based on clinical and
      echocardiographic evaluation. RESULTS: Considering only the sibling nearest in
      age for each non-twin patient the recurrence was 67/1743 (3.8%). Among these 67
      patients, 35 (52.2%) had a sibling with the same or similar CHD. Conversely,
      considering all 1886 siblings, recurrence of CHD in the non-twin group was
      70/1743 (4%). Of the 70 patients, 36 (36/70, 51.4%) had a sibling with the same
      suspected pathogenic mechanism of CHD. In 9/66 pairs of twins (13.6%), both
      siblings had a CHD. In the nine pairs of twins in whom both siblings had a CHD,
      the percentage of concordance (based on the suspected pathogenic mechanism) for
      CHD was 100% (p<0.05). CONCLUSIONS: Our findings suggest that the higher
      recurrence and concordance of CHD found in dizygotic twins could depend on some
      poorly identified environmental risk during the pregnancy.

PMID- 15982498
TI  - Visualization of pulmonary vein stenosis after radio frequency ablation using
      multi-slice computed tomography: initial clinical experience in 33 patients.
AB  - PURPOSE: Radio frequency ablation (RFA) of the pulmonary veins (PV) is an
      established technique for treatment of atrial fibrillation (AF). However,
      stenoses within the treated areas are well known complications. Thus, a reliable
      non-invasive diagnosis of PV stenosis would be an important step forward in the
      care of these patients (pts). Aim of the present study was the diagnostic
      accuracy of new multi-slice detected computed tomography (MSCT) in visualization
      of PV and in detecting PV stenosis. MATERIAL AND METHODS: A total of 33 pts (17
      male, 16 female, mean age 57+/-10.2 years [40-71]) were included. Retrospectively
      ECG-gated CT angiography (CTA) was performed within 1 day to a maximum of 380
      days after RFA with a MSCT scanner. Interpretation of the scan was performed on
      conventional contrast enhanced axial slices and on 3D volume rendering images
      (maximum intensity projection: MIP, multi-planar reconstruction: MPR). Lesion
      severity was determined on a semi-quantitative scale (mild: <20%, intermediate:
      20-50%, severe >50%) and compared to conventional angiography which had been
      performed at the beginning and at the end of RFA. RESULTS: MSCTA was applied
      without any complications, and all treated pulmonary veins (n=73) could be
      visualized. Diagnostic image quality was obtained in all examinations. A
      significant stenosis was detected by conventional angiography in 26/73 (36%) PV
      (2/73 (3%) severe, 14/73 (19%) intermediate, 10/73 (14%) mild). Using MSCTA, only
      13 stenosis in 73 treated PV could be visualized (1/73 (1%) severe, 6/73 (8%)
      intermediate, 6/73 (8%) mild). CONCLUSIONS: Multi-slice-detector CT is able to
      visualize PV and to detect PV stenoses. However, stenosis severity seems to be
      underestimated and not all lesions could be accurately detected. Larger studies
      have to be performed to further assess the diagnostic accuracy and clinical
      reliability of this new non-invasive method and to focus on the incidence of PV
      stenosis following RFA especially in long-time follow up.

PMID- 15982500
TI  - Familial biventricular myocardial noncompaction associated with Ebstein's
      malformation.
AB  - BACKGROUND: Noncompaction of the ventricular myocardium is a rare congenital
      cardiomyopathy characterized by numerous excessively prominent trabeculations and
      deep intertrabecular recesses. Noncompaction of the ventricular myocardium is
      most often an isolated cardiac malformation presenting as a sporadic disease.
      Associated cardiac anomalies are present in some patients. We report a family
      with three adult males from consecutive generations having a biventricular form
      of noncompaction of the myocardium. Two of the patients have an associated
      Ebstein's malformation of the tricuspid valve. METHODS: Clinical evaluation and
      follow-up, electrocardiography, echocardiography, heart catheterization, coronary
      angiography, contrast cineventriculography, and magnetic resonance imaging.
      RESULTS AND CONCLUSIONS: The association of noncompaction of the ventricular
      myocardium and Ebstein's malformation has not been reported so far. We believe
      that both defects were caused by a developmental arrest of the right ventricular
      myocardium. Echocardiography is the diagnostic modality of choice in patients and
      in the male relatives, irrespective of their clinical status. Thromboembolic
      events, cardiac rhythm disorders and heart failure mandate treatment.
      Anticoagulation treatment and implantation of cardioverter-defibrillator
      pacemaker have to be strongly considered in these patients.

PMID- 15982501
TI  - Bundle branch block patterns, age, renal dysfunction, and heart failure
      mortality.
AB  - BACKGROUND: The determinants of bundle block patterns and their relationship to
      mortality in heart failure patients is not completely understood. METHODS: We
      evaluated 2907 consecutive patients admitted to an intensive care unit with
      decompensated heart failure over 8 years. Clinical and echocardiographic factors
      were analyzed using multivariate techniques. All-cause mortality was available on
      greater than 99.0% of patients at a median of 23 months after discharge. RESULTS:
      Right and left bundle branch blocks occurred in 211 (7.3%) and 386 (13.2%),
      p<0.0001. Older age, decreased left ventricular ejection fraction, and renal
      dysfunction were all found to be independently associated with bundle branch
      block patterns. Mortality rates for the subgroups of QRS<120 ms, right bundle
      branch block and left bundle branch block, over a mean follow-up of 23.4+/-2.6
      months were 46.1%, 56.8% and 57.7%, p<0.0001 for comparison of QRS<120 ms versus
      either bundle pattern. Cox proportional hazards model adjusting for age, sex,
      ejection fraction, and renal function demonstrated graded decrements in survival
      in those with QRS<120 ms, right bundle branch block and left bundle branch block,
      p=0.03. CONCLUSIONS: In patients hospitalized with severe heart failure, age,
      left ventricular dysfunction, and renal dysfunction are associated with bundle
      branch block patterns. When controlling for these factors, bundle branch block
      patterns are independently associated with slightly higher all cause mortality
      after discharge.

PMID- 15982502
TI  - Association of two apolipoprotein A-I gene MspI polymorphisms with lipid and
      blood pressure levels.
AB  - INTRODUCTION: Two MspI polymorphisms in the ApoA-I gene (G-75A and C83T) have
      been shown to be associated with plasma HDL-cholesterol levels. METHODS: We used
      a PCR-based RFLP method to determine the association of these polymorphisms with
      lipid parameters in 271 non-diabetic, normotriglyceridaemic Chinese subjects, of
      whom 104 were patients with hypertension, with 10.2% having hypercholesterolaemia
      and the remainder were controls. RESULTS: As expected, the hypertensive group had
      higher blood pressure and indices of obesity, and a more adverse lipid profile.
      No differences in the ApoA-I G-75A genotype or allele frequency distributions
      between the controls and patients were identified. However, there was a
      significantly lower frequency of the CT genotype (p=0.012) and T allele (p=0.011)
      in the affected subjects with hypercholesterolaemia or hypertension. Similarly,
      blood pressure and triglyceride levels were significantly lower and HDL
      cholesterol levels significantly higher in the subjects with the CT genotype
      compared to those with the CC genotype (p<0.05). However, the G-75A genotypes did
      not appear to influence the lipid or blood pressure levels. The -75A allele
      frequency was higher in our healthy controls than an equivalent Caucasian
      population (31.1% vs. 18.3%, p<0.001), whereas the 83T allele frequency was
      similar between the healthy Chinese and Caucasian groups. CONCLUSION: The 83T
      allele may be associated with a better lipid profile and blood pressure levels in
      this group of Chinese subjects.

PMID- 15982503
TI  - Short-term evolution of vasovagal syncope: influence on the quality of life.
AB  - To evaluate the short-term evolution and changes in the quality of life (QoL) of
      patients suffering from vasovagal syncope (VVS) by the application of the Short
      Form 36 questionnaire (SF-36) that was prospectively administrated to all
      consecutive patients with syncope and abnormal response to head-up tilt test. We
      included 167 patients (55.7% women, median age 42 years old). During a 6-month
      follow-up, recurrence was observed in 33 patients (19.8%). The mean recurrence
      free time was 6.2+/-0.34 months. Among those patients with and without relapses,
      there were only differences in the previous number of syncopes (6 vs. 3,
      p=0.0051). Of them, 19 (11%) only presented 1 syncopal relapse and 14 (8.2%)
      presented more than 1. There were differences in the time until the first relapse
      [4 months (2.3-5.4) vs. 1.6 months (0.8-3.3), p=0.002] and an inverse correlation
      between the time until the appearance of recurrences and their number (r2
      Spearman=-0.54, p=0.002). In just 6 months, those patients who had recurrence had
      a worse QoL than those who did not, in 7 dimensions of the SF-36 questionnaire.
      In the short-term, one in every five patients with VVS had at least 1 relapse,
      and if it is very early, it can recur in up to 8% of them. The QoL of these
      patients is correlated with the appearance of relapses.

PMID- 15982504
TI  - Oral vitamin C administration reduces early recurrence rates after electrical
      cardioversion of persistent atrial fibrillation and attenuates associated
      inflammation.
AB  - BACKGROUND: Inflammation and oxidative stress have been recently implicated in
      the pathophysiology of atrial fibrillation (AF). The aim of this study was to
      examine the potential benefit of vitamin C on the early recurrence rates and on
      inflammatory indices after successful cardioversion of persistent AF, as well as
      to investigate the time course of changes in these indices post-cardioversion.
      METHODS: We prospectively studied 44 consecutive patients after successful
      electrical cardioversion of persistent AF. All patients received standard
      treatment and were randomised in one to one fashion to either oral vitamin C
      administration or no additional therapy. We followed-up the patients for 7 days
      performing successive measurements of white blood cell (WBC) count, C-reactive
      protein (CRP), fibrinogen, and ferritin levels. RESULTS: One week after
      successful cardioversion, AF recurred in 4.5% of patients in the vitamin C group
      and in 36.3% of patients in the control group (p=0.024). Compared to baseline
      values, inflammatory indices decreased after cardioversion in patients receiving
      vitamin C but did not change significantly in the control group. A significant
      variance was found in the serial measurements of WBC counts (F=5.86, p=0.001) and
      of fibrinogen levels (F=4.10, p=0.0084) in the two groups. In the vitamin C group
      CRP levels were lower on the seventh day (p<0.05). CRP and fibrinogen levels were
      higher in patients who relapsed into AF compared to patients who maintained sinus
      rhythm (F=2.77, p=0.044 and F=3.51, p=0.017, respectively). CONCLUSIONS: These
      findings suggest that vitamin C reduces the early recurrence rates after
      cardioversion of persistent AF and attenuates the associated low-level
      inflammation. These effects indicate that therapeutic approaches targeting at
      inflammation and oxidative stress may exert favourable effects on atrial
      electrical remodeling.

PMID- 15982505
TI  - Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C
      goal attainment in hypercholesterolemic patients with coronary heart disease.
AB  - OBJECTIVE: To determine whether co-administering ezetimibe with on-going
      simvastatin treatment was more effective than placebo plus on-going simvastatin
      in achieving an LDL-C treatment target of < or = 2.60 mmol/l (100 mg/dl) in
      hypercholesterolemic patients with coronary heart disease (CHD). METHODS: Men and
      women (age > or = 18 years) with documented CHD and on a stable dose of
      simvastatin 10 mg or 20 mg for at least 6 weeks were recruited for this study.
      After a 4-week simvastatin 10 or 20 mg plus placebo and diet run-in period,
      patients were eligible for randomization if LDL-C > 2.60 and < or = 4.20 mmol/l
      and triglycerides (TG) < or = 4.00 mmol/l. Eligible patients were randomized to a
      double-blind comparative study with ezetimibe 10 mg co-administered with on-going
      simvastatin 10 mg or 20 mg (n=181) versus placebo to match ezetimibe co
      administered with simvastatin 10 mg or 20 mg (n=191) for 6 weeks. RESULTS: At
      baseline, mean LDL-C was comparable between the ezetimibe (3.14 mmol/l) and
      placebo (3.19 mmol/l) groups. With the addition of ezetimibe or placebo to on
      going simvastatin therapy, the percentage of patients achieving the LDL-C goal of
      < or = 2.60 mmol/l after 6 weeks of treatment was significantly (p < or = 0.001)
      greater in the ezetimibe group (74.3%) than in the placebo group (16.7%). The
      addition of ezetimibe to on-going simvastatin treatment also resulted in a
      significantly (p < or = 0.001) larger mean percent reduction in LDL-C from
      baseline (25.2%) compared with placebo (0.9%). Ezetimibe was generally well
      tolerated compared to placebo when added to on-going simvastatin treatment.
      CONCLUSIONS: Co-administering ezetimibe with on-going simvastatin 10 or 20 mg
      treatment allowed more hypercholesterolemic patients with CHD to reach the LDL-C
      treatment target of < or = 2.60 mmol/l.

PMID- 15982506
TI  - Gene expression in giant cell myocarditis: Altered expression of immune response
      genes.
AB  - BACKGROUND: Giant cell myocarditis is a rapidly progressive and often fatal
      condition without a clear etiology or treatment. A better understanding of giant
      cell myocarditis pathogenesis is critical to developing treatments to prevent
      progression and reverse damage. We compared the gene expression of giant cell
      myocarditis with that of nonfailing hearts. METHODS: Left ventricular samples
      from two giant cell myocarditis patients harvested during ventricular assist
      device placement and six unused donor hearts were examined using Affymetrix U133A
      microarrays. Differential gene expression was defined with a Bonferroni-adjusted
      p value < or = 0.05 from a Student's t-test and an absolute fold change > or =
      2.0. Select gene expression was confirmed with quantitative PCR. RESULTS: Of 115
      differentially expressed genes, most were upregulated in giant cell myocarditis
      and involved in immune response, transcriptional regulation, and metabolism. T
      cell activation genes included chemokine receptor 4; chemokine ligands 5, 9, 13,
      and 18; interleukin-10 receptor alpha; and beta-2 integrin. CONCLUSIONS: Gene
      expression analysis of giant cell myocarditis offers novel insights into its
      pathogenesis, namely the role of T-cell activators of the Th1 subset and immune
      response genes previously implicated in heart failure. This forms the basis for
      future work aimed at defining novel therapeutic targets for giant cell
      myocarditis.

PMID- 15982507
TI  - Atherosclerotic double right coronary artery and ectasia of left coronary
      arteries in a patient with presented acute coronary syndrome and ventricular
      tachycardia.

PMID- 15982508
TI  - Iatrogenic left main coronary artery thrombosis during percutaneous coronary
      intervention.
AB  - During diagnostic angiographic procedures or percutaneous coronary angioplasty
      stenting of the other coronary arteries, the overall risk for a complication
      related to the left main coronary artery (LMCA) is low; however, if such
      complications occur, they tend to be life-threatening and contribute to a large
      part of the total catheter-related mortality. We encountered a case of iatrogenic
      significant subtotal left main coronary artery thrombotic stenosis in a patient
      who had undergone prior percutaneous transluminal coronary artery angioplasty
      stenting of the left circumflex artery. In light of the literature, an extremely
      rare clinical presentation of iatrogenic left main coronary artery thrombosis is
      discussed.

PMID- 15982509
TI  - Tetralogy of Fallot with absent thumb and first metacarpal.

PMID- 15982510
TI  - Transient left ventricular apical ballooning: a novel heart syndrome.
AB  - A novel cardiac syndrome of left ventricular apical ballooning (Takotsubo
      cardiomyopathy-ampulla cardiomyopathy) involves reversible left ventricular
      apical ballooning (during systole) of acute onset with chest pain,
      electrocardiographic changes, and minimal elevation of cardiac enzymes resembling
      acute myocardial infarction, but without evidence of myocardial ischemia or
      injury. Patients have no angiographic evidence of coronary artery stenosis and
      there is almost always a complete recovery of left ventricular function in days
      to weeks. The precise etiologic basic of this syndrome is not clear but most
      likely it is a non-ischemic, metabolic syndrome caused by stress-induced
      activation of the cardiac adrenoceptors in absence of ischemia and reperfusion.
      Reported here is a case of stress-induced transient left ventricular apical
      ballooning syndrome in a young woman.

PMID- 15982511
TI  - Ramipril induced polyserositis with pericardial tamponade and pleural effusion.

PMID- 15982512
TI  - Double-stenting of an ostial left main-stem lesion for elastic recoil.

PMID- 15982513
TI  - Evaluation of the diagnostic utility of ECG criteria for left ventricular
      diastolic overload.

PMID- 15982515
TI  - Multiple appropriate and spurious defibrillator shocks in a patient with right
      ventricular cardiomyopathy.
AB  - An implantable cardioverter defibrillator (ICD) has been implanted in a 69-year
      old patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) for
      treatment of syncopal ventricular tachycardia (VT). Two types of ICD-related
      emergencies complicated the clinical course within 15 months. The first
      arrhythmic event occurred 3 months after ICD implantation as electrical storm
      with repetitive fast VT, resulting in 87 consecutive shocks at maximal output.
      Intravenous administration of amiodarone and reprogramming of the device were the
      measures to control VT. A year later, the patient experienced a cluster of 97
      inappropriate shocks. Lead insulation failure produced electrical noise on the
      ventricular sensing channel and was misidentified as ventricular fibrillation
      (VF). The depleted ICD and the dual-coil lead were explanted and replaced by a
      new system. Multiple ICD shocks constitute a medical emergency in ICD patients,
      which requires immediate device interrogation for differentiation of appropriate
      and spurious discharges.

PMID- 15982514
TI  - Use of a novel high-osmolar gadolinium chelate, gadobutrol, for percutaneous
      renal artery stenting in two patients with chronic renal failure.
AB  - Gadolinium chelates have been recently proposed and preliminarily tested as
      contrast agents for diagnostic and interventional angiography in alternative to
      iodinated media. However, in most studies low-osmolarity agents were employed and
      digital subtraction was required for satisfactory images. In this article, we
      report for the first time in the literature two cases of successful percutaneous
      renal artery stenting in which gadobutrol, a high-osmolar (1 mmol/ml) gadolinium
      chelate, was employed as contrast agent because of chronic renal failure and
      substantial risk for iodinated contrast-associated nephrotoxicity. In both
      patients gadobutrol yielded high-quality images without digital subtraction and
      was well tolerated with no ensuing renal dysfunction.

PMID- 15982516
TI  - Serum-free thyroxine and thyrotropin concentrations in euthyroid patients with
      decompensated congestive heart failure.
AB  - We realized a prospective study of 106 consecutive patients hospitalized in an
      Internal Medicine Service with decompensated CHF. Between the 95 patients with
      normal serum-free thyroxine and thyrotropin concentrations, patients older than
      70 years had a significant higher serum free thyroxine concentration (13.1+/-2.6
      vs. 10.1+/-1.5 pmol/l, p=0.006) and a lower, but not significant, serum
      thyrotropin concentration (1.3+/-1.2 vs. 1.7+/-1.1 mU/l, p=0.11). No correlation
      was found between the functional class, the echocardiographic ejection fraction
      or the in-hospital stay and the serum free thyroxine and thyrotropin
      concentrations. The sex, the presence of systolic dysfunction, diastolic
      dysfunction, atrial fibrillation or comorbidity did not determine significant
      differences in the serum-free thyroxine and thyrotropin concentrations.

PMID- 15982517
TI  - WHO's role of registering trials should include acronyms too.

PMID- 15982518
TI  - Microvascular angina due to microvascular coronary vasospasm.

PMID- 15982519
TI  - A "fat" cough.

PMID- 15982520
TI  - Maximum likelihood estimation of structure parameters from high resolution
      electron microscopy images. Part I: a theoretical framework.
AB  - This paper is the first part of a two-part paper on maximum likelihood (ML)
      estimation of structure parameters from electron microscopy images. In principle,
      electron microscopy allows structure determination with a precision that is
      orders of magnitude better than the resolution of the microscope. This requires,
      however, a quantitative, model-based method. In our opinion, the ML method is the
      most appropriate one since it has optimal statistical properties. This paper aims
      to provide microscopists with the necessary tools to apply this method so as to
      determine structure parameters as precisely as possible. It reviews the
      theoretical framework, including model assessment, the derivation of the ML
      estimator of the parameters, the limits to precision and the construction of
      confidence regions and intervals for ML parameter estimates. In a companion paper
      [Van Aert et al., Ultramicroscopy, this issue, 2005], a practical example will be
      worked out.

PMID- 15982521
TI  - Maximum likelihood estimation of structure parameters from high resolution
      electron microscopy images. Part II: a practical example.
AB  - This paper is the second part of a two-part paper on maximum likelihood (ML)
      estimation of structure parameters from electron microscopy images. In order to
      show the practical applicability of the theoretical methods described in the
      first part of this two-part paper, an experimental study of an aluminium crystal
      is presented. In this study, structure parameters, atom column distances in
      particular, are estimated from high-resolution transmission electron microscopy
      (HRTEM) images using the ML method. The necessary steps to be made in the
      application of this method will be worked out one by one, including model
      assessment, the computation of the ML parameter estimates, and the construction
      of confidence intervals for these parameter estimates.

PMID- 15982522
TI  - Modelling imaging based on core-loss spectroscopy in scanning transmission
      electron microscopy.
AB  - Recent experimental realizations of atomic column resolution core-loss
      spectroscopy in the scanning transmission electron microscope have increased the
      importance of routinely modelling core-loss images. We discuss different
      approaches to wave function simulation and how they may be used in conjunction
      with the mixed dynamic form factor model to simulate images resulting from such
      inelastic scattering events. It is shown that, as resolution improves and in
      situations where the degree of thermal scattering is high, detailed quantitative
      comparisons will require the thermal scattering of electrons to be adequately
      modelled. Indeed, for sufficiently strong thermal scattering even qualitative
      interpretation may be affected: we give an example where this leads to a contrast
      reversal. We describe two methods suited to this purpose, the frozen lattice
      model and the scattering factor model, and explain how they may be combined with
      the mixed dynamic form factor approach.

PMID- 15982523
TI  - Effects of ATP-sensitive potassium channel activators diazoxide and BMS-191095 on
      membrane potential and reactive oxygen species production in isolated piglet
      mitochondria.
AB  - Mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel openers protect the
      piglet brain against ischemic stress. Effects of mitoK(ATP) channel agonists on
      isolated mitochondria, however, have not been directly examined. We investigated
      the effects of K(ATP) channel openers and blockers on membrane potential and on
      the production of reactive oxygen species (ROS) in isolated piglet mitochondria.
      Diazoxide and BMS-191095, putative selective openers of mitoK(ATP), decreased the
      mitochondrial membrane potential (delta psi(m)). On a molar basis, diazoxide was
      less effective than BMS-191095. In contrast, diazoxide but not BMS-191095
      increased ROS production by mitochondria. Since diazoxide also inhibits succinate
      dehydrogenase (SDH), we examined the effects of 3-nitropropionic acid (3-NPA), an
      inhibitor of SDH. 3-NPA failed to change the delta psi(m) but increased ROS
      production. Inhibitors of K(ATP) channels did not affect resting delta psi(m) or
      ROS production, but glibenclamide and 5-hydroxydecanoate (5-HD) blocked effects
      of diazoxide and BMS-191095 on delta psi(m) and diazoxide effects on ROS
      production. We conclude that BMS-191095 has selective effects on mitoK(ATP)
      channels while diazoxide also increases ROS production probably via inhibition of
      SDH.

PMID- 15982524
TI  - Motherhood mitigates aging-related decrements in learning and memory and
      positively affects brain aging in the rat.
AB  - The current work examined spatial learning and memory (i.e., latencies to find a
      baited food well) in age-matched nulliparous, primiparous and multiparous (NULL,
      PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We
      tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris
      water maze (Main task), and at 12, 18 and 24 months in the same task in which the
      original location of the baited well was changed (Reversal task). We show that
      PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial
      tasks significantly better and exhibited attenuated memory decline, up to 24
      months of age. Furthermore, at the conclusion of behavioral testing, we
      investigated levels of these animals' hippocampal (CA1 and dentate gyrus)
      immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and
      age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and
      DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a
      reduction in APP compared to NULLs in DG. Further, level of APP was negatively
      correlated with performance in the two tasks (viz., more APP, worse maze
      performance). Reproduction, therefore, with its attendant natural endocrine and
      postpartum sensory experiences, may facilitate lifelong learning and memory, and
      may mitigate markers of neural aging, in the rat. Combining natural hormonal
      exposure with subsequent substantial experience with stimuli from the offspring
      may preserve the aged parous female brain relative to that of NULL females.

PMID- 15982525
TI  - Gene expression profiling reveals the mechanism of action of anticonvulsant drug
      QYS.
AB  - We have examined the gene expression profiling of inferior colliculus from DBA/2J
      mice with high-intensity noise induced audiogenic seizure (AGS). We have also
      tested the effects of Qingyangshenylycosides (QYS), a traditional Chinese
      medicine, on the audiogenic seizure, and examined how the drug affected the gene
      expressions in inferior colliculus. Our results demonstrated that the latency was
      increased and the Tonus% of AGS was decreased in the animals treated with QYS,
      indicating that the drug effectively prevented audiogenic seizure. Gene
      expression analysis using Agilent oligo microarray showed that total of 134 genes
      were either up- or down-regulated during AGS. QYS prevented many of the AGS
      induced gene expression changes. Nevertheless, some of the AGS induced genes were
      further enhanced or reversed by QYS treatment. Our gene expression profiling data
      provided important information regarding the molecular mechanisms of AGS and the
      mechanism of action of QYS. Further analysis of the function of these genes may
      help to identify therapeutic targets for epilepsy.

PMID- 15982526
TI  - Dissociation of synaptic zinc level and zinc transporter 3 expression during
      postnatal development and after sensory deprivation in the barrel cortex of mice.
AB  - In the neocortex, synaptic zinc level is regulated by sensory experience.
      Previously, we found that trimming of mystacial vibrissae resulted in an increase
      of synaptic zinc level in corresponding deprived barrels in the cortex of mice.
      The present study focused on the relationship between synaptic zinc and zinc
      transporter 3 (ZnT3) protein expression in the barrel cortex of mice during
      postnatal development and after sensory deprivation of selected vibrissae. Using
      immunocytochemistry and western blot analysis, we found that ZnT3 expression is
      delayed as compared with the onset of synaptic zinc and presynaptic markers, such
      as synapsin I and synaptophysin. Further, neither long-term deprivation in young
      mice nor short deprivation in adult mice, that resulted in an increase of
      synaptic zinc level, produced alterations in ZnT3, synapsin I or synaptophysin
      expression in deprived barrels. These results suggest that in the barrel cortex
      ZnT3, synapsin I or synaptophysin are not determinant for the activity-dependent
      regulation of the synaptic zinc level.

PMID- 15982527
TI  - Effects of sleep disruption on rat dentate granule cell LTP in vivo.
AB  - Sleep frequently fragmented or disrupted for prolonged periods can result in mood
      changes and impaired mental ability and performance. Sleep deprivation is defined
      as depriving a person or organism of sleep for various periods of fixed
      durations. Sleep disruption (SD) occurs when a person is awakened at any time
      when they would normally be sleeping; sometimes on a schedule but usually
      unexpectedly. It seems as if any disruption of an entrained sleep pattern can
      induce learning and memory impairment; and mood changes including irritability
      and aggression. Because memory is impaired under these conditions several studies
      have been conducted recently to examine changes in long term potentiation (LTP)
      in hippocampal brain slices following various periods of sleep deprivation in
      rats. Results of the present study show clearly that LTP is also decreased
      following SD but to a greater extent than that observed following sleep
      deprivation. The purpose of the present study was to measure dentate granule cell
      LTP in anesthetized rats following 1-, 2-, or 3-day schedules of SD using a
      modified flower pot procedure. Results showed that a single disruption of 3 h
      reduced LTP from a normal 38.7-7.6%; that endured for at least 14 h; and 9 h
      reduced it completely. Easy to handle animals become irritable, hyperactive, and
      aggressive following SD. Results are discussed in terms of stress related effects
      of SD and changes in synaptic plasticity.

PMID- 15982528
TI  - Grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic
      brain injury in neonatal rats.
AB  - Oxygen radicals play a crucial role in brain injury. Grape seed extract is a
      potent anti-oxidant. Does grape seed extract reduce brain injury in the rat pup?
      Seven-day-old rat pups had the right carotid arteries permanently ligated
      followed by 2.5 h of hypoxia (8% oxygen). Grape seed extract, 50 mg/kg, or
      vehicle was administered by i.p. 5 min prior to hypoxia and 4 h after
      reoxygenation and twice daily for 1 day. Brain damage was evaluated by weight
      deficit of the right hemisphere at 22 days following hypoxia and by
      histopathology. Grape seed extract reduced brain weight loss from 20.0+/-4.4%
      S.E.M. in vehicle pups (n=21) to 3.1+/-1.6% in treated pups (n=20, P<0.01). Grape
      seed extract improved the histopathologic brain score in cortex, hippocampus and
      thalamus (P<0.05 versus vehicle). Concentrations of brain 8-isoprostaglandin
      F2alpha and thiobarbituric acid reacting substances significantly increased due
      to hypoxic ischemia. Grape seed extract reduced this increase. Treatment with
      grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic
      brain injury in neonatal rat.

PMID- 15982529
TI  - Rapid and long-term plasticity in the neonatal and adult retinotectal pathways
      following a retinal lesion.
AB  - The uncrossed retinotectal projection restricts its terminal fields to the
      ventral boundary of the visual layers at the rostral tectum during early post
      natal development. During this critical period, temporal retinal lesions in one
      eye induce laminar rearrangements in the uncrossed pathway of the intact eye
      toward the collicular surface previously occupied, almost exclusively, by the
      crossed retinal axon population. We have compared, using anterograde tracing
      techniques, the time course and magnitude of the axonal sprouting resulting from
      retinal lesions in neonates and adults. Early retinal lesions (within the first
      two post natal weeks) induced extensive and rapid plasticity of the ipsilateral
      projection 48 h after the lesions. On the third post natal week, similar retinal
      lesions induced a small reorganization of the intact eye's uncrossed projection
      within a 3-week survival time. Nevertheless, giving the animals a long-term
      survival, resulted in an increased plastic capability, suggesting that even after
      the critical period, intact retinal axons can respond efficiently to injury. The
      results suggest two phases of axonal reorganization within this subcortical
      pathway: a rapid plasticity within the critical period and a slow, but continuous
      plasticity in adulthood.

PMID- 15982530
TI  - Increased fiber outgrowth from xeno-transplanted human embryonic dopaminergic
      neurons with co-implants of polymer-encapsulated genetically modified cells
      releasing glial cell line-derived neurotrophic factor.
AB  - We investigated whether a continuous supply of glial cell line-derived
      neurotrophic factor (GDNF) via encapsulated genetically modified cells can
      promote survival and fiber outgrowth from xenotransplanted human dopaminergic
      neurons. Cells genetically engineered to continuously secrete GDNF were confined
      in hollow fiber-based macrocapsules. Each hemiparkinsonian rat received either a
      single C2C12-hGDNF capsule (n=8) or a C2C12-control capsule (n=8) concomitantly
      with human embryonic ventral mesencephalic cell suspension transplants. Our
      results show that fiber outgrowth in the area between the capsule and the graft
      is more extensive in rats with GDNF-releasing capsules than in rats with control
      capsules. We suggest that continuous and safe delivery of GDNF to the brain could
      be a potential way to optimize neural transplantation as a therapy for
      Parkinson's disease.

PMID- 15982531
TI  - Changes in brain temperature and thermoregulation produced by destruction of
      medial septal neurons in rats.
AB  - Brain temperatures (Tbr) of male Wistar rats were recorded at every 15 min
      interval for 24 h, prior to the destruction of the medial septal (MS) neurons
      with N-methyl-D-aspartic acid, and on the 7th, 14th and 21st days after the
      destruction. The capacity of the rats to regulate their body temperature under
      severe cold and heat was assessed by recording their Tbr when they were exposed
      to 5+/-1 and 37+/-1 degrees C for 2 h, before lesion and on 8th, 9th, 15th, 16th,
      22nd and 23rd days after the lesion. The Tbr was decreased and its circadian
      variation increased after the MS lesion. On exposure to an ambient temperature of
      5+/-1 degrees C the Tbr was decreased on 9th and 16th days after the lesion, when
      compared with the sham lesion group on identical days, though the fall in
      temperature was not significant on the 23rd day. The change in Tbr (compared with
      the sham lesion group) was not significantly different on all days of exposure to
      37+/-1 degrees C. The decrease in Tbr after the MS lesion is in contrast to the
      hyperthermia produced by lesion of the adjoining thermoregulatory areas. The
      present findings suggest that the MS lesions caused an alteration in the set
      point of body temperature, without drastic changes in thermoregulatory ability.

PMID- 15982532
TI  - A low-protein diet alters rat behavior and neurotransmission in normothermic and
      hyperthermic environments.
AB  - Dietary protein contains amino acids used in the brain for synthesis of
      neurotransmitters. Although information on pre- and post-natal exposure to low
      protein diets in rodents is available, little is known about effects of such
      diets on adult animals. Therefore, the behavioral and neurochemical consequences
      of exposure to a brief (11 days), low (4%)-protein diet in animals exposed to
      normothermic and hyperthermic test conditions were examined. In separate groups
      of animals, the Porsolt Swim test and elevated plus maze were administered. These
      tasks are sensitive to nutritional and/or environmental manipulations. In other
      groups of rats exposed to the same dietary and environmental conditions,
      dopamine, norepinephrine, epinephrine, and serotonin in the striatum were
      assessed using microdialysis. In the Porsolt swim test, which assesses coping
      behavior, performance was impaired under normothermic and hyperthermic conditions
      in animals on the low-protein diet. Performance on the plus maze, a measure of
      exploration and anxiety, was altered in the hyperthermic condition by low
      protein, with the diet increasing exploration. Microdialysis detected increased
      norepinephrine in the striatum of hyperthermic animals on the low-protein diet.
      This study demonstrates that changes in stress-related behaviors of adult animals
      occur following brief exposure to low-protein diets.

PMID- 15982533
TI  - Exploratory activity and motor coordination in wild-type SOD1/SOD1 transgenic
      mice.
AB  - SOD1 is one of several overexpressed genes in trisomy 21. In order to dissect
      possible genetic causes of the syndrome, wild-type SOD1/SOD1 transgenic mice were
      compared to FVB/N non-transgenic controls at 5 months of age in tests of
      exploratory activity and motor coordination. Wild-type SOD1/SOD1 transgenic mice
      had fewer stereotyped movements in an open-field and fell sooner from a rotorod
      than controls. In contrast, wild-type SOD1/SOD1 transgenic mice had fewer falls
      on a wire suspension test. There was no intergroup difference for ambulatory
      movements in the open-field, exploration of the elevated plus-maze, emergence
      from a small compartment, and motor coordination on a stationary beam. These
      results indicate that homozygous mice expressing human SOD1 are impaired in their
      ability to adjust their posture in response to a moving surface and make fewer
      small-amplitude movements without any change in general exploratory activity.

PMID- 15982534
TI  - Effects of foreperiod duration on anticipatory postural adjustments:
      determination of an optimal preparation in standing and sitting for a raising arm
      movement.
AB  - The purpose of the present experiment was to examine the motor and postural
      preparation processes evolving during the foreperiod (known to be optimal at 500
      ms in sitting) in a voluntary upper limb movement executed while standing. The
      foreperiod duration (300, 500, 700 and 900 ms) and the postural conditions
      (sitting versus standing) were manipulated using a priming procedure. Two types
      of prime were provided: (1) a prime giving valid information on the side of the
      raising arm movement to execute, and (2) a prime giving non-valid information
      (prime opposite to the required side). In a sitting and standing condition, eight
      normal subjects performed a raising arm movement with a 1 kg load at the level of
      the wrist. Premotor time and acceleration of arm movement were recorded in the
      two postural conditions. In the standing condition, anticipatory postural
      adjustments (APAs) were also quantified using the relative latency of
      electromyographic (EMG) data and the centre of foot pressure (CoP) displacements.
      Results (1) showed that the optimal foreperiod duration (i.e., leading to the
      shortest premotor time) increased as a function of postural conditions (500
      versus 700 ms in the sitting and standing conditions, respectively), and (2)
      emphasized the existence of a temporal modulation in the central organization of
      the postural and focal commands according to the foreperiod duration.

PMID- 15982535
TI  - Intelligence related upper alpha desynchronization in a semantic memory task.
AB  - Recent evidence shows that event-related (upper) alpha desynchronization (ERD) is
      related to cognitive performance. Several studies observed a positive, some a
      negative relationship. The latter finding, interpreted in terms of the neural
      efficiency hypothesis, suggests that good performance is associated with a more
      'efficient', smaller extent of cortical activation. Other studies found that ERD
      increases with semantic processing demands and that this increase is larger for
      good performers. Studies supporting the neural efficiency hypothesis used tasks
      that do not specifically require semantic processing. Thus, we assume that the
      lack of semantic processing demands may at least in part be responsible for the
      reduced ERD. In the present study we measured ERD during a difficult verbal
      semantic task. The findings demonstrate that during semantic processing, more
      intelligent (as compared to less intelligent) subjects exhibited a significantly
      larger upper alpha ERD over the left hemisphere. We conclude that more
      intelligent subjects exhibit a more extensive activation in a semantic processing
      system and suggest that divergent findings regarding the neural efficiency
      hypotheses are due to task specific differences in semantic processing demands.

PMID- 15982537
TI  - Diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes
      characterized by hyperglycemia, ketosis and acidosis. The pathophysiology of DKA
      is reviewed and diagnostic and therapeutic modalities are discussed in the
      context of the currently available evidence. Complications associated with DKA
      are often a result of the treatment itself, and these issues are also discussed.

PMID- 15982538
TI  - Hyperosmolar hyperglycemic state.
AB  - Hyperosmolar hyperglycemic state (HHS) is the most serious acute complication of
      type 2 diabetes mellitus. Emergency department management focuses on prompt
      diagnosis and restoration of hemodynamic stability with appropriate fluid therapy
      while maintaining electrolyte homeostasis. Identification of any precipitating
      illness is essential. The emergence of HHS as a critical presentation of type 2
      diabetes mellitus in adolescents is highlighted.

PMID- 15982539
TI  - Hypothyroidism: mimicker of common complaints.
AB  - Hypothyroidism is a common condition presenting a challenge to emergency
      physicians in diagnosing the underlying etiology of vague complaints. Making the
      diagnosis of a critically ill patient in myxedema coma allows early treatment
      with appropriate thyroid hormone replacement and avoids higher patient mortality.
      To do this, the emergency physician must maintain a high degree of clinical
      suspicion for thyroid disease.

PMID- 15982540
TI  - Hyperthyroidism.
AB  - The clinical spectrum of hyperthyroidism varies from asymptomatic,subclinical
      hyperthyroidism to the life-threatening "thyroid storm". Hyperthyroidism is a
      common form of thyroid disease that mimics many of the common complaints in the
      emergency department. The diagnosis of hyperthyroidism is often challenging due
      to the multitude of physical and even psychiatric complaints. Recognition and
      treatment by emergency physicians of severe hyperthyroidism is critical and can
      be life saving.

PMID- 15982541
TI  - Recognition and management of adrenal emergencies.
AB  - Although clinical conditions associated with dysfunction of the ad-renal gland
      are often subtle, even insidious, in their presentation,and diagnosis and
      treatment usually are confined to outpatient clinics and offices, there are
      several situations that warrant the attention of emergency physicians.
      Recognition of the spectrum of presentations of pheochromocytoma, adrenal
      insufficiency, and pituitary apoplexy, and the sequelae of corticosteroid therapy
      and withdrawal, are critically important areas to emergency medicine. Prompt
      diagnosis with appropriate treatment and referral will reduce morbidity and
      mortality in many patients each year. A related topic pertinent to emergency
      physicians is the management of incidental adrenal masses that are discovered on
      abdominal radio-logic imaging.

PMID- 15982542
TI  - Bone and mineral metabolism.
AB  - Although bones are normally thought of as supporting structures that fracture
      when one falls, bone is actually a very active metabolic organ. It is vital in
      the regulation of calcium and phosphate metabolism, magnesium storage, and in
      buffering metabolic acido-sis. Bone and mineral metabolism and some of their
      disorders are presented in this article.

PMID- 15982543
TI  - Disorders of potassium.
AB  - Potassium disorders are the most common electrolyte abnormality identified in
      clinical practice. Presenting symptoms are similar for both hypo- and
      hyperkalemia, primarily affecting the cardiac, neuromuscular, and
      gastrointestinal systems. Generally, mild hypokalemia is the most common
      potassium disorder seen clinically;however, severe complications can occur.
      Hyperkalemia is less common but more serious, especially if levels are rising
      rapidly. The etiologies and treatments for both hypo- and hyperkalemia are
      discussed, with special emphasis on the role medications play in the etiologies
      of each.

PMID- 15982544
TI  - Disorders of water imbalance.
AB  - Disorders of water imbalance manifest as hyponatremia and hypernatremia. To
      diagnose these disorders, emergency physicians must maintain a high index of
      suspicion, especially in the high-risk patient, because clinical presentations
      may be nonspecific. With severe water imbalance, inappropriate fluid
      resuscitation in the emergency department may have devastating neurological
      consequences. The rate of serum sodium concentration correction should be
      monitored closely to avoid osmotic demyelination syndrome in hyponatremic
      patients and cerebral edema in hypernatremic patients.

PMID- 15982545
TI  - Differential diagnosis of metabolic acidosis.
AB  - Metabolic acidosis is defined as an acidemia created by one of three mechanisms:
      increased production of acids, decreased excretion of acids, or loss of alkali.
      This article addresses the identification and correct diagnosis of metabolic
      acidosis by reviewing important historical factors, pathophysiological
      principles, clinical presentation,and laboratory findings accompanying common
      high and normal anion gap metabolic acidoses in emergency department patients.

PMID- 15982546
TI  - Disorders of fuel metabolism: medical complications associated with starvation,
      eating disorders, dietary fads, and supplements.
AB  - Disorders of fuel metabolism as they relate to abnormal fuel intake,abnormal fuel
      expenditure, and dietary supplements are the focus of this article. The emergency
      physician should be aware of the medical complications that can occur as a result
      of starvation states,eating disorders, fad diets, hypermetabolic states, and
      ergogenic aids. Knowledge and understanding of the complications associated with
      these disorders will facilitate the diagnosis and management of patients who
      present to the emergency department with any of the disorders reviewed.

PMID- 15982547
TI  - Anabolic steroids: what should the emergency physician know?
AB  - Anabolic steroids have not currently made their way into the daily practice of
      emergency physicians. The patients that use and abuse them have. In addition,
      those patients that are suffering from the consequences of illnesses that have
      excess levels of androgens are commonly evaluated in the emergency department.
      Clinicians should familiarize themselves with the practices of anabolic steroid
      users, so they can provide more beneficial council to their patients. As research
      continues, the emergency physician may find uses for androgens within the
      emergency department.

PMID- 15982548
TI  - External causes of metabolic disorders.
AB  - Common medical conditions, such as head trauma, malignancy,and pregnancy may be
      associated with rarely seen metabolic emergencies that require prompt recognition
      and therapy. Although care of the primary disorder is the focus of initial
      management,identification of the associated endocrinopathy is important. These
      clinical syndromes, although uncommon, must be considered when evaluating
      patients, as prompt treatment may minimize the mortality and morbidity of these
      conditions.

PMID- 15982549
TI  - The emergency department approach to newborn and childhood metabolic crisis.
AB  - For most emergency medicine physicians, the phrases "newborn workup" and
      "metabolic disease" are, at best, uncomfortable. This article, however, provides
      a simple approach to the recognition,evaluation, and treatment of infants with
      all manners of metabolic issues, including hypoglycemia, inborn errors of
      metabolism, jaundice, and electrolyte abnormalities. The disorders are grouped
      based on symptomatology, and have simple guidelines for work-up and management,
      with an emergency department practitioner perspective in mind.

PMID- 15982550
TI  - The porphyrias.
AB  - The porphyrias are a group of disorders involving enzymatic defects in heme
      synthesis. The porphyrias classically manifest neuro-visceral or photocutaneous
      symptoms based on which enzyme in the heme metabolic pathway is deficient.
      Although rare, the porphyrias would most likely be encountered in the emergency
      department in patients presenting with chronic unspecified abdominal or
      musculoskeletal pain and those with new onset of psychiatric complaints.

PMID- 15982551
TI  - Altered mental status due to metabolic or endocrine disorders.
AB  - The differential diagnoses for mental status alteration is broad. Endocrine or
      metabolic causes for emergency department patients who present with lethargy,
      anxiety, psychosis, and seizures should be considered. Using the complaint-based
      approach, this article discusses some of the often less obvious etiologies for
      these presentations related to endocrine and metabolic disease states.

PMID- 15982552
TI  - The endocrine response to critical illness: update and implications for emergency
      medicine.
AB  - This review will provide an updated overview of the neuroendocrine response to
      critical illness. Specifically, the current evidence for "stress steroid"
      administration will be examined, as well as interventional glucose control during
      critical illness. The emergency physician will also find relevance in the
      alterations of thyroid hormones that occur in the face of severe illness or
      trauma.

PMID- 15982553
TI  - Transplant immunology--separate issue clinical immunogenetics and cell therapy.

PMID- 15982554
TI  - Features of MHC and NK gene clusters.
AB  - When comparing the immune genome to the genome in general, a higher prevalence
      for association with disease is the only genetic feature significant in immune
      genes as a group. However, some genetic features, such as marked levels of
      polymorphism and gene duplication, are present in subsets of immune genes, namely
      the Major Histocompatibility Complex (MHC) and Natural Killer (NK) cell receptor
      gene complexes. In this review, we discuss features of MHC and NK receptor gene
      clusters, their epistatic interactions, and the impact of both on association to
      disease.

PMID- 15982555
TI  - KIR genes.
AB  - This review updates the on-going investigations into KIR genes and their alleles
      with the main emphasis on what has taken place in this laboratory over the last 3
      years.

PMID- 15982556
TI  - The molecular genetics of blood group polymorphism.
AB  - Nearly 300 blood group specificities on red cells are known, many of which are
      polymorphic. The molecular mechanisms responsible for these polymorphisms are
      diverse, though the majority represent single nucleotide polymorphisms (SNPs)
      encoding amino acid substitutions. Other mechanisms include the following: gene
      deletion; single nucleotide deletion and sequence duplication, which introduce
      reading-frame shifts; nonsense mutation; intergenic recombination between closely
      linked genes, giving rise to hybrid genes and hybrid proteins; and a SNP in the
      promoter region of a blood group gene. Examples of these genetic mechanisms are
      taken from the ABO, Rh, Kell, and Duffy blood group systems. Null phenotypes, in
      which no antigens of a blood group system are expressed, are not generally
      polymorphic, but provide good examples of the effect of inactivating mutations on
      blood group expression. As natural human 'knock-outs' they provide useful clues
      to the functions of blood group antigens. Knowledge of the molecular bases to
      blood group polymorphisms provides a means to predict blood group phenotype from
      genomic DNA with a high degree of accuracy. This currently has two main
      applications in transfusion medicine: for determining fetal blood groups to
      assess whether the fetus is at risk from haemolytic disease; and to determine
      blood group phenotypes in multiply transfused, transfusion-dependent patients,
      where serological tests are precluded by the presence of donor red cells. Other
      applications are being developed for the future.

PMID- 15982557
TI  - Milestones in immunohematology.
AB  - The milestones in immunohematology, as seen by immunogeneticists, are described.

PMID- 15982558
TI  - Is the ABO incompatibility a risk factor in bone marrow transplantation?
AB  - ABO histo-bloodgroups are strong transplantation antigens. In bone marrow
      transplantation, foreign ABO red cell antigens are not ignored by the immune
      system of the host, neither by the immunocompetent cells of the graft. Although
      ABO incompatibility is not considered a contraindication in bone marrow
      transplantation (BMT), its clinical consequences are still a matter of
      investigation. An overview of reports published by different groups is given and
      discussed. They present conflicting data regarding the role of the ABO match
      between patient and donor in the haematopoietic stem cell (HSC) transplantation.
      We report on the clinical outcome of bone marrow transplantation in 223 patients
      who received grafts from MHC identical siblings. Included are 139 ABO identical,
      32 ABO minor mismatched, 34 major mismatched and 13 bi-directionally mismatched
      pairs. The statistical evaluation of standard parameters used to monitor the post
      transplant period gave a proof that in neither group of patients with an ABO
      incompatible donor the recovery and success rate of transplantation, including
      the relapse incidence, risk of graft vs. host disease (GVHD) or overall survival,
      were significantly inferior. However, in all three cohorts of ABO mismatched
      patients, a delayed recovery of neutrophils was recorded as compared to the group
      receiving an ABO compatible graft. These finding leads us to the conclusion that
      the ABO compatibility is not a disadvantage in BMT, whereas the delayed recovery
      of neutrophils in patients having received an ABO mismatched graft is probably
      reflecting a transient humoral process leading to immune tolerance and graft
      accommodation.

PMID- 15982559
TI  - Antigen processing is predictable: From genes to T cell epitopes.
AB  - In order to induce a cellular immune response, antigens have to be processed in
      intracellular compartments, transported, and presented by HLA molecules prior to
      recognition by specific T cells. Many of the events that contribute to antigen
      processing have been thoroughly investigated during the past years and are now
      well understood, which lead to a number of prediction programs. "Reverse
      immunology" has been used for about 10 years in order to identify T cell epitopes
      from pathogens or tumor-associated antigens. The advantages and pitfalls of T
      cell epitope prediction compared to classical experimental procedures such as
      epitope mapping and cloning experiments have been discussed many times. In this
      presentation, a number of internet programs that offer help in T cell epitope
      prediction (or prediction of antigen processing) will be discussed in the light
      of transfusion medicine. Some databases are listing published HLA ligands and T
      cell epitopes, others offer epitope prediction for many HLA class I or class II
      restrictions. In addition, a number of established programs will be demonstrated
      which are freely accessible at no cost in the world wide web for the prediction
      of either HLA-peptide binding, proteasomal processing of antigens, or both.
      Epitope prediction and processing prediction programs will be applied to minor
      histocompatibility antigens (miHAgs) and compared. This reflects the actual
      possibilities and limitations of such computer-aided work not only in cellular
      immunology, but also in transplantation immunology.

PMID- 15982560
TI  - HLA associated genetic predisposition to autoimmune diseases: Genes involved and
      possible mechanisms.
AB  - Autoimmune diseases are the result of an interplay between predisposing genes and
      triggering environmental factors, leading to loss of self-tolerance and an immune
      mediated destruction of autologous cells and/or tissues. Genes in the HLA complex
      are among the strongest predisposing genetic factors. The HLA complex genes
      primarily involved are most often those encoding the peptide-presenting HLA class
      I or II molecules. A probable mechanism is preferential presentation by the
      disease-associated HLA molecules of peptides from autoantigens to T cells. Recent
      studies have shown, however, that other genes in the HLA complex also contribute.
      Taken together, available evidence suggests that the HLA complex harbour both
      disease predisposing genes which are quite specific for some autoimmune diseases
      (e.g. HLA-B27 for ankylosing spondylitis) and others which may be more common for
      several diseases. This will be briefly reviewed in the following.

PMID- 15982561
TI  - Host genetics and the outcome of hepatitis B viral infection.
AB  - Hepatitis B Virus (HBV) infection can result in numerous different clinical
      outcomes. A complex combination of environment, and viral and host genetic
      factors play a critical role in determining both susceptibility to HBV
      persistence and the course of infection. Evidence is presented that suggests that
      host genetic factors play an important role in determining the outcome of HBV
      infection. This data from various groups demonstrates that multiple genes play a
      role in determining hepatitis B viral clearance or persistence. However, to
      identify all the relevant variants that affect the outcome of infection,
      alternative strategies such as genome-wide association studies with large sample
      sizes will be required to define the majority of the relevant polygenes.

PMID- 15982562
TI  - Differential immunogenicity of HLA mismatches in clinical transplantation.
AB  - Although HLA matching is beneficial in clinical transplantation, it is not
      feasible to select a completely HLA matched donor for every potential recipient
      because of the enormous polymorphism of the HLA system. As a consequence, the
      majority of the recipients will be transplanted with a mismatched donor organ or
      hematopoietic stem cell transplant. For this large group of patients it is
      important to take advantage of the differential immunogenicity of HLA mismatches
      and to select for them a donor with HLA mismatches of low immunogenicity, the so
      called acceptable mismatches. The differential immunogenicity of HLA mismatches
      can be determined by either retrospective analysis of graft survival data or by
      in vitro assays measuring T-cell and B-cell alloreactivity. A recently developed
      computer algorithm (HLAMatchmaker) can be instrumental in selecting donors with
      HLA mismatches, which do not lead to alloantibody formation. The theoretical
      background and practical implications of this acceptable mismatch approach are
      discussed.

PMID- 15982563
TI  - Prognostic assays for rejection and tolerance in organ transplantation.
AB  - In this review, I have summarised our understanding of acute rejection of organ
      transplants, and for convenience I have identified three processes, recognition,
      rejection and regulation. In stark contrast to this text-book picture of acute
      rejection, I have drawn attention to some of the clinical realities, where
      processes are altered by powerful immunosuppressive drugs, and where many
      transplant recipients are pre-sensitised to transplantation antigens prior to
      engraftment. The ultimate goal is to encourage the emergence of a utopian
      immunological state, wherein patients tolerate organ transplants for life after
      being weaned from all immunosuppressive drugs. Assays that may be used in the
      future to reliably monitor this process are still at a very exciting stage of
      development.

PMID- 15982564
TI  - The impact of donor natural killer cell alloreactivity on allogeneic
      hematopoietic transplantation.
AB  - Although natural killer (NK) cells are triggered to kill by many activating
      receptors, lysis of autologous cells is blocked by inhibitory receptors (called
      Killer cell Ig-like receptors or KIRs) which recognize epitopes shared by certain
      major histocompatibility complex (MHC) class I allele groups (called KIR
      ligands). As these inhibitory receptors are clonally distributed, they
      constituted a repertoire containing different allospecificities. Thus, the NK
      cells in the repertoire are lytic against allogeneic targets that do not express
      their inhibitory KIR ligands. In hematopoietic human-leukocyte-antigen (HLA)
      haplotype mismatched transplantation, donor-vs-recipient alloreactive NK cells
      improve engraftment, decrease the incidence of leukemia relapse and do not cause
      Graft-vs-Host disease (GvHD). Pre-transplant molecular high-resolution HLA of
      recipient and donor, KIR genotyping of the donor and direct assessment of the
      donor NK repertoire identify donors with the potential for donor-vs-recipient NK
      cell alloreactivity.

PMID- 15982565
TI  - Nonmyeloablative stem cell transplantation and cell therapy for malignant and non
      malignant diseases.
AB  - The conditioning prior to allogeneic stem cell transplantation was originally
      designed as a myeloablative conditioning, designed to eliminate malignant or
      genetically abnormal cells and then use the transplant procedure for rescue of
      the patients or to replace missing bone marrow products. However, allografts can
      induce effective graft vs. malignancy effects and can also eliminate undesirable
      hematopoietic stem cells in patients with genetic disorders and autoimmune
      diseases, thus documenting that alloreactive effects mediated by donor
      lymphocytes post-grafting can play a major role in eliminating hematopoietic cell
      of host origin, as well as provide effective immunotherapy for the treatment of
      disease recurrence. The efficacy of donor lymphocyte infusion (DLI) could be
      improved by activation with rIL-2 or by donor immunization. The cumulative
      experience over the years suggesting that alloreactive donor lymphocytes were
      most effective in eliminating tumor cells of host origin resulted in an attempt
      to reduce the intensity of the conditioning in preparation for the transplant
      procedure used for the treatment of hematological and other malignancies as well
      as life-threatening non-malignant disorders for which allogeneic stem cell
      transplantation may be indicated. Our working hypothesis proposed that the
      myeloablative conditioning which is hazardous and may be associated with early
      and late side effects, may not be required for treatment of patients with any
      indication for allogeneic stem cell transplantation. Instead, nonmyeloablative
      conditioning based on the use of reduced intensive preparatory regimen, also
      known as nonmyeloablative stem cell transplantation, may be sufficient for
      engraftment of donor stem cells while avoiding procedure-related toxicity and
      mortality, followed by elimination of undesirable cells of host origin by post
      transplant effects mediated by alloreactive donor lymphocytes infused along with
      donor stem cells or administered subsequently as DLI. Improvement of the
      immediate outcome of stem cell transplantation using NST due to a significant
      decrease in transplant related mortality has broadened the spectrum of patients
      eligible for allogeneic stem cell transplantation, including elderly patients and
      other patients with less than optimal performance status. Likewise, the safer use
      of stem cell transplantation prompted expanding the scope of potential
      indications for allogeneic stem cell transplantation, such as metastatic solid
      tumors and autoimmune disorders, which now are slowly becoming much more
      acceptable. Current strategies focus on the need to improve the capacity of donor
      lymphocytes to eliminate undesirable malignant and non-malignant hematopoietic
      cells of host origin, replacing abnormal or malignant stem cells or their
      products with normal hematopoietic stem cells of donor origin, while minimizing
      procedure-related toxicity and mortality and improving the quality of life by
      reducing the incidence and severity of hazardous acute and chronic GVHD.

PMID- 15982566
TI  - Adult stem cell therapy beyond haemopoietic stem cell transplantation? An update.
AB  - The lifesaving potential of haemopoietic stem cell transplantation for the
      treatment of haematological malignancies and other life threatening disorders of
      the haemopoietic stem cell is universally accepted. In contrast, the use of adult
      marrow derived stem cells for tissue repair strategies in degenerative disease or
      after tissue damage are only in the early stages of evolution. A range of opinion
      exists within the general public and the scientific community about whether
      research with human embryonic stem cells is ethically acceptable. Further, the
      current paucity of human embryonic stem cell data has lead investigators to
      consider adult marrow as a potential source of stem cells to treat a wide range
      of degenerative disease and damaged tissues. Target disorders include
      osteoarthritis, diabetes mellitus, Parkinson's disease, ischaemic heart disease
      and retinal degeneration. Obvious advantages of this approach, if successful,
      would be fewer ethical hurdles compared with embryonic stem cells. Treatment with
      the patients own marrow stem cells would eliminate the possibility of allogeneic
      rejection.

PMID- 15982567
TI  - Induction of transplantation tolerance-the potential of regulatory T cells.
AB  - Solid organ transplantation is widely accepted as an effective treatment for end
      organ failure. Although the treatment with immunosuppressive drugs has
      undoubtedly greatly improved graft survival, chronic rejection still has
      considerable impact on long term outcome. This, together with the undesirable
      side effects associated with life long treatment with immunosuppressive drugs,
      have significant implications for long term outcomes. In a small number of
      patients, drug non-compliance as well as controlled reduction or removal of
      maintenance immune suppressive drug therapy has led to the uncovering of a
      tolerant state. The challenge of achieving improved monitoring of all transplant
      patients may allow tailoring of immunosupression in a proportion of recipients
      thereby increasing the opportunities for the induction of specific
      unresponsiveness to donor alloantigens in the future. The immune system using
      several mechanisms to both induce and maintain tolerance to alloantigens,
      including the deletion of allo-reactive T cells, the induction of anergy, clonal
      exhaustion, ignorance and active suppression (immunoregulation) of allo
      responses. A minor subpopulation of CD4+ T cells, regulatory or suppressor CD4+ T
      cells that co-express the cell-surface molecule CD25 (IL2 alpha subunit) at a
      high level may play a major role in the maintenance of specific unresponsiveness
      and operational tolerance to donor antigens in vivo. Intensive investigation of
      these cells in recent years has started to uncover the mechanisms of active
      suppression by regulatory T cells in this setting.

PMID- 15982569
TI  - Introduction to statistical analysis of population data in immunogenetics.
AB  - We review the most classical questions addressed by the analysis of population
      data in immunogenetics. Basic genetics' definitions are reminded. Questions
      related to the population data itself (structure, missing values nomenclature,
      sampling) are developed first, and secondly, the population genetics questions
      (relevance of genetic parameters (phenotype, genotype allele and haplotype
      frequencies; genetic distances; linkage disequilibrium measures), methods and
      practical computing) are illustrated by immunogenetics polymorphisms. This
      article gives the essential of population immunogenetics on examples and key
      references. We underline the importance of population dimension in statistical
      analysis: structure of linkage disequilibrium and genetic diversity between
      populations may affect the power of the study or the interpretation of
      correlations between markers, genes and diseases, making population genetics both
      theoretical and very practical.

PMID- 15982568
TI  - In vitro preparation and functional assessment of human monocyte-derived
      dendritic cells-potential antigen-specific modulators of in vivo immune
      responses.
AB  - Dendritic cells (DCs) are highly specialized professional antigen presenting
      cells that have a potent capacity for stimulating naive, memory and effector T
      cells. They are located in lymphoid organs as well as in almost all nonlymphoid
      tissues. Immature DCs, residing in the host microenvironment, respond to danger
      signals with maturation, a differentiation process along which they acquire the
      ability to direct the extent and the type of primary immune responses according
      to the type of danger perceived. In this review we present some of our approaches
      and experiences regarding the isolation of human monocytes from peripheral blood
      and the in vitro preparation of, first, immature and then mature DCs by applying
      several maturation factors: bacterial lipopolysaccharide (LPS), a defined mixture
      of recombinant pro-inflammatory cytokines, monocyte conditioned medium (MCM) and
      TNF-alpha alone. The assessment of DC phenotypes and their functional
      capabilities as well as some of the techniques used for tumour associated antigen
      loading are also presented. The results of such studies represent a basis for
      optimal in vitro preparation of DCs, which could be clinically used to modulate
      immune responses in cancer, autoimmune diseases and in the planned onset of
      tolerance to disparate major histocompatibilty complex (MHC) antigens prior to
      tissue or organ transplantation.

PMID- 15982570
TI  - Strategies in analysis of the genetic component of multifactorial diseases;
      biostatistical aspects.
AB  - Complex polygenic and multifactorial diseases remain a challenge for human
      geneticists. Here we aim to remind basic definitions of multifactorial diseases
      and the genetic related concepts underlying classical methods. Knowledge on
      pathophysiological process and the genetic information available conditions the
      design of study. The choice of methodology, between candidate gene approach and
      genome scan approach, between linkage and association studies, is the most
      important step. Both methods, linkage analysis and association studies are
      usually considered as complementary approaches for a given disease. For this
      reason, in this article, we present the most important classical methodologies in
      genetic epidemiology of complex disorders. References and examples are given to
      illustrate.

PMID- 15982571
TI  - Carbon-11 labeled sigma2 receptor ligands for imaging breast cancer.
AB  - Four conformationally flexible benzamide analogs having a high affinity and
      outstanding selectivity for sigma(2) versus sigma(1) receptors were synthesized
      and radiolabeled with carbon-11 by reaction with [(11)C]methyl iodide. The four
      (11)C-labeled radiotracers were evaluated for their potential to image the
      proliferative status of breast tumors with positron emission tomography (PET). In
      vivo studies in female BALB/C mice bearing EMT-6 breast tumors showed that one
      radiotracer, (2-methoxy-(11)C)-N-(4-(3,4-dihydro-6,7-dimethoxy-isoquinolin-2(1H)
      yl)butyl)-5-methylbenzamide ([(11)C]2), had a high tumor uptake and suitable
      tumor/background ratio for imaging purposes. Blocking studies were consistent
      with the labeling of sigma(2) receptors in vivo. A study comparing the in vivo
      properties of [(11)C]2 and (18)F-3'-fluoro-3'-deoxy-L-thymidine ([(18)F]FLT)
      indicated that [(11)C]2 had either similar (lung, fat) or better (blood, muscle)
      tumor/organ ratios than [(18)F]FLT in the tissues that are important for breast
      tumor imaging. Consequently, [(11)C]2 is a potential radiotracer for imaging the
      proliferative status of breast tumors in vivo with PET.

PMID- 15982572
TI  - In vitro and in vivo evaluation of [123I]-VEGF165 as a potential tumor marker.
AB  - One of the research challenges in oncology is to develop new biochemical methods
      for noninvasive tumor therapy evaluation to determine whether the
      chemotherapeutics is effective. Vascular endothelial growth factor (VEGF) was
      labeled with radioiodine and evaluated in vitro as well as in vivo, using A2058,
      a melanoma cell line overexpressing VEGFR-1 and -2. Saturation binding analysis
      with [(125)I]-VEGF resulted in a K(d) of 0.1 nM. Internalization assays indicate
      the preserved ligand induced internalization and metabolization of the tracer.
      Biodistribution studies with [(123)I]-VEGF in wild type and A2058 tumor-bearing
      athymic mice showed low background activity and a tumor to reference tissue ratio
      of maximum 6.12. These results suggest that [(123)I]-VEGF is a potentially
      suitable tracer for tumor therapy evaluation.

PMID- 15982573
TI  - Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for
      imaging the role of PARP-1 in necrosis.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of
      eukaryotic cells that has been implicated in response to DNA injury. PARP-1
      detects single-strand DNA breaks induced by a variety of genotoxic insults. A
      hyperactivation of PARP-1 is believed to play a critical role in tissues
      undergoing cellular death by necrosis. Therefore, a radiotracer that could image
      PARP-1 levels with PET could provide a useful tool in measuring necrosis in a
      variety of pathological conditions. The phenanthridinone derivative, 2
      (dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a
      high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET
      radiotracer development. The synthesis of [(11)C]PJ34 was accomplished by base
      catalyzed reaction of the corresponding des-methyl precursor, N-(5,6-dihydro-6
      oxophenanthridin-2-yl)-2-(methylamino)acetamide with [(11)C]methyl iodide in DMF.
      The radiolabeling yield was 60% and the specific activity was approximately 2000
      mCi/micromol (decay corrected to E.O.B.). The total radiosynthesis time was
      approximately 50 min. Preliminary in vivo biodistribution studies in a rodent
      model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues
      where PARP-1 is hyperactivated. These data indicate that [(11)C]PJ34 may be a
      useful radiotracer for imaging tissues undergoing cellular death via necrosis.

PMID- 15982574
TI  - FDG-PET in the detection of early pancreatic cancer in a BOP hamster model.
AB  - BACKGROUND: The prognosis of pancreatic cancer (PC) is highly dependent on the
      stage of the disease, and early recognition improves survival. Positron emission
      tomography (PET) using (18)F-fluoro-2-deoxyglucose ([(18)F]FDG) has been
      established as an important clinical tool for PC diagnosis, but it is not known
      whether FDG-PET detects premalignant stages of PC. We speculate that [(18)F]FDG
      uptake precedes the onset of PC in a hamster model. We used the N-nitrosobis(2
      oxopropyl)amine (BOP) model, as these animals consistently develop PC within 20
      weeks after first injection. METHODS: Male Syrian hamsters were injected once a
      week with 10 mg BOP/kg body weight for 10 consecutive weeks. Terminal autopsy
      took place in groups of five hamsters from 4 weeks until 28 weeks after first BOP
      injection. After an 8-h fast, hamsters were injected with [(18)F]FDG and
      sacrificed 1 h after [(18)F]FDG injection. The pancreata were histopathologically
      examined, and the [(18)F]FDG uptake was determined and expressed as percentage of
      the injected dose per gram tissue (%ID/g). RESULTS: Seven of 55 hamsters
      developed macroscopic signs of tumor. Histopathological examination revealed PC
      in 13 hamsters. [(18)F]FDG uptake increased gradually with time and was
      significantly higher in the group with PC compared to the group without PC.
      CONCLUSION: [(18)F]FDG accumulates preferentially in PC, and pancreata exposed to
      BOP showed a gradual increase in [(18)F]FDG accumulation.

PMID- 15982575
TI  - Uptake in melanoma cells of N-(2-diethylaminoethyl)-2-iodobenzamide (BZA2), an
      imaging agent for melanoma staging: relation to pigmentation.
AB  - N-(2-diethylaminoethyl)-2-iodobenzamide (BZA(2)) has been singled out as the most
      efficacious melanoma scintigraphy imaging agent. Our work was designed to assess
      the mechanisms of the specific affinity of the radioiodinated iodobenzamide for
      melanoma tissue. We studied the cellular uptake and retention of [(125)I]-BZA(2)
      on various cell lines. In vitro, cellular [(125)I]-BZA(2) uptake was related to
      the pigmentation status of the cells: higher in pigmented melanoma cell lines (M4
      Beu, IPC 227, B 16) than in a nonpigmented one (M3 Dau) and nonmelanoma cell
      lines (MCF 7 and L 929). Two mechanisms were assessed: binding of the tracer to
      melanin or to sigma receptors of melanoma cells. First, the uptake of [(125)I]
      BZA(2) after melanogenesis stimulation by alpha-melanocyte-stimulating hormone
      and l-tyrosine increased in the B 16 melanoma cell line both in vitro and in vivo
      according to melanin concentration. Moreover, the binding of [(125)I]-BZA(2) to
      synthetic melanin was dependent on melanin concentration and could be saturated.
      Second, no competition was evidenced on M4 Beu cells between [(125)I]-BZA(2) and
      haloperidol, a sigma ligand, at concentrations < or =10(-6) M. We show that the
      specificity and sensibility of BZA(2) as a melanoma scintigraphic imaging agent
      are mostly due to interactions with melanic pigments.

PMID- 15982576
TI  - A human osteosarcoma cell line expressing herpes simplex type-1 thymidine kinase:
      studies with radiolabeled (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine.
AB  - INTRODUCTION: (E)-5-(2-Iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) is a
      pyrimidine nucleoside analogue that accumulates selectively in murine cells
      expressing herpes simplex type-1 thymidine kinase (HSV-1 TK). The uptake of
      [(125)I]IVFRU in human 143B osteosarcoma cells transduced with a retroviral
      vector bearing the HSV-1 TK gene (143B-LTK cells) is now reported. METHODS: HSV-1
      TK gene expression in 143B-LTK cells was confirmed by Western blotting and
      reverse transcriptase (RT)-PCR. Cell and subcellular uptake of [(125)I]IVFRU was
      determined in cell culture, and whole body biodistribution after intravenous
      injection of [(125)I]IVFRU was determined using nude mice bearing implanted 143B
      or 143B-LTK tumors. RESULTS: Although IVFRU was less toxic to the human cell line
      expressing HSV-1 TK (143B-LTK) than ganciclovir, both IVFRU and ganciclovir were
      not toxic to the cell line not expressing HSV-1 TK (143B). When cells were
      exposed to [(125)I]IVFRU in vitro, only the 143B-LTK cells accumulated
      radioactivity. The acid-soluble fraction from 143B-LTK cell lysates contained 8
      fold greater activity than the acid-insoluble fraction after an 8-h exposure to
      [(125)I]IVFRU. Biodistribution of [(125)I]IVFRU in nude mice bearing subcutaneous
      143B and 143B-LTK tumors revealed widespread distribution of the nucleoside in
      vivo but with specific localization in 143B-LTK tumors. CONCLUSION: The
      underlying biochemical process of metabolic entrapment of IVFRU in human
      osteosarcoma cells expressing HSV-1 TK is responsible for selective localization
      in these cells. The differences in subcellular distribution into the nucleic acid
      fraction, and in cytotoxicity, reflect the importance of cell type and lineage as
      determinants of the performance of gene imaging radiopharmaceuticals.

PMID- 15982577
TI  - Correlation between 99mTc-MIBI uptake and angiogenesis in MIBI-positive breast
      lesions.
AB  - This study was undertaken to assess the correlation between the degree of
      accumulation and the washout of 99m technetium methoxyisobutylisonitrile ((99m)Tc
      MIBI) and angiogenesis in MIBI-positive breast lesions. Twenty-eight patients
      (mean age, 51+/-11 years) with 31 breast lesions who underwent scintimammography
      were studied. Anterior, left and right prone lateral images were obtained 20 min
      and 3 h after the injection of 740 MBq (99m)Tc-MIBI. All breast lesions showed
      increased (99m)Tc-MIBI uptake. Early and delayed tumor to background activity
      ratios (T/BG) and washout index (early tumor uptake-delayed tumor uptake divided
      by early tumor uptake) were calculated. Vascular endothelium was
      immunohistochemically labeled using a biotinylated monoclonal antibody directed
      against the factor-VIII-associated antigen using standard biotin-avidin
      technique. Angiogenesis was evaluated by assessing the vascular surface density
      (VSD) and the microvessel number (NVES) within 10 randomly chosen areas. All
      pathological data were compared with early and delayed T/BG activity ratios and
      washout index of (99m)Tc-MIBI. Statistical analysis was performed using Spearman
      correlation test. There was no statistically significant correlation between the
      degree of angiogenesis and early T/BG (r = .287, P > .05 with VSD, r = .351, P >
      .05 with NVES), delayed T/BG (r = .277, P > .05 with VSD, r = .315, P > .05 with
      NVES) and the washout index (r = .268, P > .05 with VSD, r = .285, P > .05 with
      NVES) of (99m)Tc-MIBI in all breast lesions. There was no statistically
      significant correlation between the degree of angiogenesis and early T/BG (r =
      .235, P > .05 with VSD, r = .356, P > .05 with NVES), delayed T/BG (r = .181, P >
      .05 with VSD, r = .285, P > .05 with NVES) and the washout index (r = .158, P >
      .05 with VSD, r = .187, P > .05 with NVES) of (99m)Tc-MIBI in 24 invasive breast
      lesions. No statistically significant correlation was found between the degree of
      angiogenesis and early T/BG (r = -.036, P > .05 with VSD, r = -.107, P > .05 with
      NVES), delayed T/BG (r = -.500, P > .05 with VSD, r = -.429, P > .05 with NVES),
      but there was a high correlation between angiogenesis and the washout index (r =
      .893, P < .05 with VSD, r = .964, P < .05 with NVES) of (99m)Tc-MIBI in seven
      noninvasive breast lesions. Amount of (99m)Tc-MIBI uptake in breast lesions is
      dependent on several factors. Our study indicates that early and delayed (99m)Tc
      MIBI uptakes in MIBI-positive breast lesions are not related to angiogenesis in
      both invasive and noninvasive breast lesions. But washout index of (99m)Tc-MIBI
      in noninvasive breast lesions is highly correlated with angiogenesis. (99m)Tc
      MIBI scintigraphy does not seem to be able to indicate angiogenic property of
      invasive breast lesions.

PMID- 15982578
TI  - Picolylamine-methylphosphonic acid esters as tridentate ligands for the labeling
      of alcohols with the fac-[M(CO)3]+ core (M = 99mTc, Re): synthesis and
      biodistribution of model compounds and of a 99mTc-labeled cobinamide.
AB  - [(Methyl-pyridin-2-ylmethyl-amino)-methyl]-phosphonic acid is a new bifunctional
      chelator for the fac-[(99m)Tc(CO(3))](+) core which can be linked to biomolecules
      via formation of phosphonic acid esters. Its synthesis and the coupling to model
      alcohols and to a bioactive molecule (cobinamide) are described. The rhenium
      complexes [Re(CO)(3)L] of the esters have been prepared and characterized, one of
      them by X-ray crystallography. The model esters could be labeled with
      [(99m)Tc(OH(2))(3)(CO)(3)](+) under mild conditions and relatively low ligand
      concentration with >97% yield and only one isomer formed. The (99m)Tc-labeled
      cobinamide analog was a mixture of four isomers. It bound strongly to
      transcobalamin I (TC I, haptocorrin) but only slightly to transcobalamin II (TC
      II) and intrinsic factor (IF), reflecting the binding abilities of cobinamide.
      Biodistribution studies in mice with B(16) melanoma exhibited fast clearance with
      no specific tissue binding.

PMID- 15982579
TI  - Tumor-targeting properties of 90Y- and 177Lu-labeled alpha-melanocyte stimulating
      hormone peptide analogues in a murine melanoma model.
AB  - The purpose of this study was to compare the tumor-targeting properties of (90)Y
      DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH in a murine melanoma
      mouse model. METHODS: The in vitro properties of cellular internalization and
      retention of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were
      studied in B16/F1 murine melanoma cells. The pharmacokinetics of (90)Y-DOTA
      Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were determined in B16/F1
      melanoma-bearing C57 mice. RESULTS: (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA
      Re(Arg(11))CCMSH exhibited fast cellular internalization and extended cellular
      retention in B16/F1 cells. High receptor-mediated tumor uptake and retention
      coupled with fast whole-body clearance of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu
      DOTA-Re(Arg(11))CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The
      tumor uptakes of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH
      were 25.70 +/- 4.64 and 14.48 +/- 0.85 %ID/g at 2 h, and 14.09 +/- 2.73 and 17.68
      +/- 3.32 %ID/g at 4 h postinjection. There was little activity accumulated in
      normal organs except for kidney. CONCLUSIONS: High tumor-targeting properties of
      (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH highlighted their
      potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma
      in further investigations.

PMID- 15982580
TI  - Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with
      [11C]-labeled fatty acids.
AB  - METHODS: Anesthetized pigs were studied with [(11)C]-labeled fatty acids (FAs)
      with carbon chain length ranging from 8 to 16 carbon atoms, during control
      conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I)
      with oxfenicine. The myocardial uptake of [(11)C]-FAs from blood was measured
      together with the relative distribution of [(11)C]-acyl-CoA between rapid
      mitochondrial oxidation and incorporation into slow turnover lipid pools in the
      heart. RESULTS: During baseline conditions, the fractional oxidative utilization
      of palmitate was almost as high as that of carnitine-independent short-chain FAs,
      unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition
      of CPT I almost completely blocked the oxidative pathway for palmitic acid and
      reduced the fractional oxidative utilization, while the rate of oxidative
      metabolism of acyl-CoA was unaffected. CONCLUSIONS: [(11)C]-Labeled FAs allow
      rapid oxidation to be well separated from esterification into slow turnover lipid
      pools in the heart of anaesthetized pigs. The fractional oxidative utilization of
      [(11)C]-palmitate serves well to characterize, in vivo, the carnitine-dependent
      transfer of long-chain FAs.

PMID- 15982581
TI  - Axonal transport of rubidium and thallium in the olfactory nerve of mice.
AB  - Following intranasal administration of radioactive (86)Rb(+) and (201)Tl(+) in
      mice, we observed this direct transport via the olfactory nerve pathway. The
      (86)RbCl and (201)TlCl solutions were administered to two groups of mice, the
      unilateral intranasal and intravenous administration groups. After sacrifice,
      their heads were divided into the right and left side, which were then subdivided
      into seven parts; the nasal mucosa and brain regions were separated. Following
      the unilateral intranasal administration, uptake after 6 h by the olfactory bulb
      was significantly higher on the ipsilateral side ((86)Rb, 0.7 %dose; (201)Tl, 0.5
      %dose) than on the contralateral side ((86)Rb, 0.08 %dose; (201)Tl, 0.15 %dose).
      Moreover, the (86)Rb and (201)Tl that accumulated in the olfactory bulb were
      gradually transported to other brain regions of the olfactory tract, the
      telencephalon and the diencephalon on the side corresponding to the nostril used
      for administration. Significant differences were observed between the right and
      left side of the brain regions 6 and 12 h after administration. Further, (201)Tl
      autoradiography clearly showed striped patterns of dense accumulation, localized
      in the region around the glomerular layer and granule cell layer of the olfactory
      bulb and around the olfactory cortex. These results provide clear evidence of
      axonal transport via the olfactory nerve pathway, from nasal cavity to the
      olfactory bulb, as well as to the olfactory cortex through the synaptic
      junctions. The olfactory transport of the (86)Rb(+) and (201)Tl(+) is thought to
      represent the behavior of K(+) in the olfactory system.

PMID- 15982582
TI  - Deferoxamine as a chelator for 67Ga in the preparation of antibody conjugates.
AB  - (67)Ga antibodies (Abs) have been shown to be effective agents for single-cell
      killing due to the Auger electrons emitted, but their specific activities have
      not been as high as desired. We therefore evaluated deferoxamine (DFO) as a
      chelator, as opposed to the cyclic chelator NOTA, which was used previously. Use
      of DFO for Ab conjugation to (67)Ga was reported previously by several
      laboratories. DFO was conjugated to Abs by two methods, one using Ablysine
      conjugation and another using mild reduction of Abs to generate thiols in the
      hinge region. Labeling with (67)Ga was efficient, and the specific activities
      obtained under nonoptimized conditions were twice as high as those achieved
      previously. However, analysis of these conjugates revealed two problems that
      appear to prevent their further development. First, the stability was inadequate
      for the 3-day half-life of the nuclide. Second, the labels were poorly retained
      within cells after Ab internalization and catabolism. Also, it was found that
      stability was significantly affected by the incubation buffer used: buffers
      lacking physiological concentrations of divalent cations Ca and Mg resulted in
      much lower stability than buffers including them. In conclusion, DFO does not
      seem to be a suitable chelator for (67)Ga conjugation for our purposes.

PMID- 15982583
TI  - Evidence for reduced arterial plasma input, prolonged lung retention and reduced
      lung monoamine oxidase in smokers.
AB  - We have previously found that smokers have reduced brain monoamine oxidase (MAO)
      A and B using positron emission tomography (PET) and the irreversible mechanism
      based radiotracers [(11)C]-labeled clorgyline (CLG) and deprenyl (DEP) and their
      deuterated analogs (D CLG, D DEP). More recently, we have estimated MAO A and B
      activity in other organs using the deuterium isotope effect to determine binding
      specificity for MAO and a three-compartment model to estimate k(3), the model
      term proportional to MAO A activity. Here, we have investigated the robustness of
      the model term k(3) for estimating lung MAO A and B in light of our unexpected
      finding that lung MAO activity (k(3)) was reduced for smokers relative to
      nonsmokers, although radiotracer uptake in the lungs was similar at peak and
      plateau for the two groups. METHODS: Time-activity data from lung and arterial
      plasma were used from seven nonsmokers and seven smokers scanned previously with
      CLG and D CLG, and five nonsmokers and nine smokers scanned previously with DEP
      and D DEP. The measured time-activity curves for lung and plasma and the
      integrals for the arterial plasma time-activity curves were compared at an early
      time point (2.5 min) and at the end of the study (55 min). A three-compartment
      irreversible model was used to estimate the differences between smokers and
      nonsmokers, and the stability of the parameter (k(3)) while varying model
      assumptions for the relative fractions of lung tissue, blood and air in the PET
      voxel. RESULTS: The peak in the arterial plasma input function and the integral
      of the arterial plasma time-activity curve over the first 2.5 min after
      radiotracer injection were significantly lower for smokers relative to nonsmokers
      for all four tracers. However, although the peak and plateau of the lung time
      activity curves were similar for smokers and nonsmokers, the decline in
      radioactivity from peak to plateau was slower for smokers for all tracers. Using
      a three-compartment irreversible model, we estimated the ratio of MAO subtypes A
      and B in normal lung tissue to be on the order of 3 to 1 (MAO A to B) and that
      smokers have reduced MAO levels for both subtypes as measured by the model
      parameter, k(3). The values of k(3) are insensitive to model assumptions of
      variations in air and tissue fraction in the PET voxel. Most of the effects of
      changes in these fractions are absorbed into the parameter K(1), which governs
      the plasma-to-tissue transfer of tracer and is a function of blood flow. K(1) was
      found to be larger in smokers, although the values depend upon model assumptions
      of air and tissue fractions. k(3) was found to be significantly lower in smokers;
      for CLG, a 50% reduction in MAO A for both CLG and D CLG was observed. For DEP,
      k(3) was also significantly lower in smokers with a reduction of approximately
      80% in lung MAO B, although there was a very large coefficient of variation in
      the smoker's k(3). We also found larger values of lambda (K(1)/k(2)) for smokers
      relative to nonsmokers for all tracers consistent with a longer lung retention of
      the nonenzyme-bound tracer, which explains the slower decline in uptake from peak
      radioactivity for smokers. CONCLUSIONS: The measured arterial input function
      values for smokers and nonsmokers are significantly different for these two
      tracer pairs for nonsmokers and smokers particularly for the first few minutes
      after radiotracer injection. Model estimates of k(3) that indicate that smokers
      have lower lung MAO A and B activity than nonsmokers are robust and insensitive
      to variations in model assumptions for relative fractions of lung tissue, blood
      and air in the PET voxel. Although we have only investigated the behavior of
      [(11)C]clorgyline and [(11)C]l-deprenyl and their deuterium-substituted analogs
      in this report, the extent to which reduced arterial input and longer lung
      retention also hold for other tracers for subjects who smoke merits
      investigation.

PMID- 15982584
TI  - Modeling and analysis of PET studies with norepinephrine transporter ligands: the
      search for a reference region.
AB  - The development of positron emission tomography (PET) ligands for the
      norepinephrine transporter (NET) has been slow compared to the development of
      radiotracers for others systems, such as the dopamine (DAT) or the serotonin
      transporters (SERT). The main reason for this appears to be the high nonspecific
      (non-NET) binding exhibited by many of these tracers, which makes the
      identification of a reference region difficult. With other PET ligands the use of
      a reference region increases the reproducibility of the outcome measure in
      test/retest studies. The focus of this work is to identify a suitable reference
      region or means of normalizing data for the NET ligands investigated. METHODS: We
      have analyzed the results of PET studies in the baboon brain with labeled
      reboxetine derivatives (S,S)-[(11)C]O-methyl reboxetine (SS-MRB), (S,S)
      [(18)F]fluororeboxetine (SS-FRB) as well as O-[(11)C]nisoxetine and N
      [(11)C]nisoxetine (NIS), and, for comparison, the less active (R,R) enantiomers
      (RR-MRB, RR-FRB) in terms of the distribution volume (DV) using measured arterial
      input functions. RESULTS: (1) For a given subject, a large variation in DV for
      successive baseline studies was observed in regions with both high and low NET
      density. (2) The occipital cortex and the basal ganglia were found to be the
      regions with the smallest change between baseline (SS-MRB) and pretreatment with
      cocaine, and were therefore used as a composite reference region for calculation
      of a distribution volume ratio (DVR). (3) The variability [as measured by the
      coefficient of variation (CV) = standard deviation/mean] in the distribution
      volume ratio (DVR) of thalamus (to reference region) was considerably reduced
      over that of the DV using this composite reference region. (4) Pretreatment with
      nisoxetine (1.0 mg/kg 10 min prior to tracer) in one study produced (in
      decreasing order) reductions in thalamus, cerebellum, cingulate and frontal
      cortex consistent with known NET densities. (5) [(11)C]Nisoxetine had a higher
      background non-NET binding (DV) than the other tracers reported here with basal
      ganglia (a non-NET region) higher than thalamus. CONCLUSIONS: The reboxetine
      derivatives show a lot of promise as tracers for human PET studies of the
      norepinephrine system. We have identified a strategy for normalizing DVs to a
      reference region with the understanding that the DVR for these tracers may not be
      related to the binding potential in the same way as, for example, for the
      dopamine tracers, since the non-NET binding may differ between the target and
      nontarget regions. From our baboon studies the average DVR for thalamus (n = 18)
      for SS-MRB is 1.8; however, the lower limit is most likely less than 1 due to
      this difference in non-NET binding.

PMID- 15982585
TI  - Synthesis and initial PET imaging of new potential NK1 receptor radioligands 1-[2
      (3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[11C]methyl-piperazine and
      {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic
      acid [11C]methyl ester.
AB  - The NK(1) receptor radioligands 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl
      ethyl]-4-[(11)C]methyl-piperazine ([(11)C]BMP, [(11)C]) and {4-[2-(3,5-bis
      trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid
      [(11)C]methyl ester ([(11)C]BME, [(11)C]) were synthesized for evaluation as new
      potential PET imaging agents for brain NK(1) receptors. The new tracers
      [(11)C]BMP and [(11)C]BME were prepared by N-[(11)C]methylation and O
      [(11)C]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl
      benzyloxy)-1-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl
      benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid using [(11)C]methyl
      triflate and isolated by solid-phase extraction (SPE) purification procedure with
      40-55% radiochemical yields, decay corrected to end of bombardment, and a
      synthesis time of 15-20 min. The initial PET dynamic studies of the tracers
      [(11)C] and [(11)C] in rats were performed using an animal PET scanner, IndyPET
      II, developed in our laboratory. The results show the tracer [(11)C]BMP had
      better uptake in the animal brain than the tracer [(11)C]BME and gave higher
      quality rat brain images. Blocking studies by intravenous coinjection of hot
      tracer [(11)C]BMP with cold drug BMP had no effect on [(11)C]BMP-PET rat brain
      imaging. Likewise, blocking studies by intravenous coinjection of hot tracer
      [(11)C]BME with cold drug BME also showed no effect on [(11)C]BME-PET rat brain
      imaging. These results suggest that the localization of [(11)C]BMP and [(11)C]BME
      in rat brain is mediated by nonspecific processes, and the visualization of
      [(11)C]BMP-PET and [(11)C]BME-PET on rat brain is related to nonspecific binding.

PMID- 15982586
TI  - Fully automated one-pot synthesis of [18F]fluoromisonidazole.
AB  - A (18)F-labeled fluoromisonidazole (1H-1-(3-[(18)F]fluoro-2-hydroxypropyl)-2
      nitroimidazole, [(18)F]FMISO) was prepared via a one-pot, two-step synthesis
      procedure using a modified commercial Tracerlab FX(F-N) synthesis module.
      Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl)-2
      O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol using no-carrier-added
      [(18)F]fluoride, followed by hydrolysis of the protecting group with 1 mol/L HCl
      and purification with Sep-Paks instead of HPLC, gave [(18)F]FMISO. The overall
      radiochemical yield with no decay correction was greater than 40%, the whole
      synthesis time was less than 40 min and the radiochemical purity was greater than
      95%. The new automated synthesis procedure can be applied to the fully automated
      synthesis of [(18)F]FMISO using a commercial FDG synthesis module.

PMID- 15982587
TI  - Thoracic epidural anesthesia does not improve the incidence of arrhythmias after
      transthoracic esophagectomy.
AB  - OBJECTIVE: The incidence of arrhythmias related to an esophagectomy is high, and
      its clinical significance has been well accepted. Thoracic epidural anesthesia
      (TEA) can modulate the sympathetic tone and neuroendocrine responses associated
      with major operation. This study was aimed to evaluate the effects of TEA on the
      incidence of arrhythmias in transthoracic esophagectomy patients. METHODS: The
      records of 185 patients who underwent the Ivor-Lewis operation between 2001 and
      2004 by the same operator were reviewed. The patients were divided into three
      groups. Group 1 (n = 58) received post-operative intravenous patient-controlled
      analgesia without TEA. Group 2 (n = 55) received postoperative epidural patient
      controlled analgesia using local anesthetics. The patients of group 3 (n = 72)
      were anesthetized intra-operatively by the combination technique of thoracic
      epidural bupivacaine and inhalation agents, and post-operative pain control was
      done in the same way with group 2. RESULTS: Arrhythmias occurred 29.3, 50 and
      29.2% in groups 1, 2 and 3, respectively. There were no statistical differences
      in the incidences of arrhythmias among the three groups. CONCLUSIONS: This result
      shows that TEA was not beneficial to reduce the incidence of arrhythmias in the
      transthoracic esophagectomy patients.

PMID- 15982588
TI  - Homograft reconstruction of the aortic root for endocarditis with periannular
      abscess: a 17-year study.
AB  - OBJECTIVE: The study was conducted to evaluate the long-term results of homograft
      reconstruction of the left ventricular outflow tract with a cryopreserved aortic
      homograft in the presence of aortic root abscess associated with a biofilm
      bacterial infection. METHODS: Between January 1987 and December 2003, 161
      patients with aortic root abscess underwent freehand aortic valve (FAVR, N = 78)
      and aortic root replacement (ARR, N = 83) with an antibiotic treated
      cryopreserved aortic homograft. Their mean age was 53.1+/-15.6 years.
      Endocarditis of the native valve was found in 80 patients and of the prosthetic
      valve in 81; of the prosthetic valves 49 (60.5%) were mechanical and 32 (39%)
      bioprosthetic. Aortic ventricular discontinuity was found in 83 patients. The
      common responsible microorganisms were the biofilm bacteria: Staphylococcus (S.
      epidermidis: 34, S. aureus: 13) in 47 patients followed by Enterococcus in 23 and
      Streptococcus in 39. Surgery was urgent in 80 patients and emergent in 81, of
      whom 44 were in cardiogenic shock. Follow-up totaled 810.8 patient-years (mean:
      5.0+/-4.3 years) and was 100% complete. RESULTS: Operative mortality was 9.3% for
      elective/urgent and 14.3% for emergency surgery. A total of 7.3% patients died
      after hospital discharge during the 17-year follow-up period. The actuarial
      patient survival at 17 years was 70.4+/-3.6%. Early and late residual/recurrent
      infections and paravalvular leaks occurred in 4.3 and 2.5%, respectively.
      Reoperations were carried out in 30 patients, 11 for residual/recurrent infection
      and paravalvular leaks. Twenty-one patients with FAVR and 9 with ARR techniques
      underwent reoperation. Early reoperation rate was 4.3%. The actuarial freedom
      from residual/recurrent infection and paravalvular leaks was 91.6+/-2.4%.
      Actuarial freedom from reoperation at 17 years was 75+/-3.7%. It was 82.9+/-5.5%
      for ARR and 63.5+/-6.7% for AAVR technique. The actuarial freedom from structural
      valve deterioration (SVD) at 17 years was 98.6+/-0.4.% at a rate of %/patient
      year. CONCLUSIONS: Radical debridement of the infected aortic root and homograft
      ARR offer a low recurrent infection rate and an overall low valve-related
      morbidity and mortality for up to 17 years. The antibiotic permeable
      cryopreserved homograft has proven to be resistant to biofilm bacterial
      infection.

PMID- 15982589
TI  - Comparison of bipolar and unipolar radiofrequency ablation in an in vivo
      experimental model.
AB  - OBJECTIVE: Linear atrial radiofrequency lesions have been used effectively for
      the treatment of atrial fibrillation. In most cases an endocardial approach has
      been suggested. A method for epicardial placement of lesions would reduce the
      complexity of these procedures. We compared lesions created in ovine hearts in
      vivo using irrigated bipolar or unipolar handheld radiofrequency ablation
      devices. METHODS: Radiofrequency lesions were produced around a left pulmonary
      vein, around the left atrial appendage and in the free wall of the right
      ventricle in ovine hearts. All lesions were created in the beating heart. A
      bipolar clamping device (n = 7) or a handheld unipolar device (n = 6) was used.
      Measurements of local electrograms and pacing thresholds were performed before
      and after ablation at each site to assess the electrical integrity of lesions.
      Tetrazolium and digital image analysis were used to assess lesion geometry.
      RESULTS: In atrial tissue continuous transmural lesions were achieved more often
      with the bipolar than with the unipolar device (92.3 vs. 33.3%, P < 0.02). In
      atrial tissue the reduction in signal amplitude caused by the lesions was
      significantly larger with the bipolar than the unipolar device (87.6+/-9.4% vs.
      60.6+/-23.7% reduction, P < 0.01). There was a significant relationship between
      loss of pacing capture and lesion transmurality (P < 0.05). The bipolar device
      created narrower lesions than the unipolar device (4.1+/-0.9 mm vs. 5.9+/-2.1 mm,
      P < 0.001). CONCLUSIONS: The bipolar clamping device produces narrower lesions
      which are more likely to be transmural and lead to electrical isolation of
      ablated tissue than those produced by the unipolar device. However, both devices
      failed to consistently produce transmural lesions using the epicardial beating
      heart technique studied, particularly in thicker tissues. High output pacing
      within the ablated tissue partially predicts lesion transmurality and be a guide
      to the need for further ablation. However, endocardial ablation or transmural
      bipolar ablation are likely to remain the techniques of choice for linear
      radiofrequency ablation in the atria until improved techniques are developed.

PMID- 15982591
TI  - Is mitral valve surgery safe in octogenarians?
AB  - OBJECTIVE: To evaluate the outcomes of mitral valve surgery in octogenarians.
      METHODS: Data were collected prospectively from January 1996 to March 2004 at two
      surgical centers. Of 1386 consecutive patients with mitral valve surgery, 58
      (4.2%) were aged > or = 80 years. Survival data were analyzed using Cox
      proportional hazards modeling and Kaplan-Meier actuarial log rank statistics.
      RESULTS: Octogenarians were similar to younger patients for the presence of pre
      operative hypertension, hyperlipidemia, diabetes mellitus, and smoking history.
      Octogenarians had a higher incidence of cerebrovascular disease (19.0 versus
      7.8%, P = 0.003), urgent in-hospital surgery (55.2 versus 28.6%, P < 0.001), and
      presence of ischemic disease requiring combined mitral valve plus
      revascularization surgery (72.4 versus 41.0%, P < 0.001). Mitral valve repair was
      performed in a similar proportion of octogenarians and younger patients (44.8
      versus 45.6%). Thirty-day mortality for octogenarians was significantly higher
      than younger patients (15.5 versus 5.6%, P = 0.002), and actuarial survival of
      octogenarians was significantly decreased (P = 0.009). However, 52.3% of the
      octogenarians were alive at 7-years following surgery. Independent predictors of
      mortality from multivariate risk adjusted modeling of the entire cohort were:
      emergency surgery (hazards ratio [HR] = 2.94, P < 0.001), combined mitral valve
      plus revascularization surgery (HR = 2.27, P < 0.001), mitral valve replacement
      (HR = 1.85, P < 0.01), and age > or = 80 years (HR = 1.80, P = 0.02).
      CONCLUSIONS: Octogenarians undergoing mitral valve surgery have significantly
      greater incidence of urgent surgery, ischemic disease requiring combined
      revascularization surgery, and have decreased rates of survival. While caution is
      required when operating on these higher risk elderly patients, overall 52.3% of
      the octogenarians are alive at 7-years following surgery, which is greater than
      the survival of octogenarians in the community. The greatest survival benefit
      within octogenarians occurred when mitral valve repair was possible over
      replacement. Further study will more clearly define subgroups of octogenarians
      with potentially greater benefit from mitral valve surgery.

PMID- 15982592
TI  - Comparison of neurocognitive results after coronary artery bypass grafting and
      thoracic aortic surgery using retrograde cerebral perfusion.
AB  - OBJECTIVE: Retrograde cerebral perfusion (RCP) is used as an adjunctive method to
      hypothermic circulatory arrest to enhance cerebral protection in patients
      undergoing thoracic aortic surgery. It remains unclear whether RCP provides
      improved neurological and neuropsychological outcome. METHODS: Forty-six patients
      undergoing thoracic aortic surgery using RCP, and 28 undergoing coronary artery
      bypass grafting (CABG; n = 28) with CPB, were enrolled in the study. Patients
      receiving RCP were subdivided into two groups, those with less than 60 min of RCP
      (S-RCP; n = 27) and with 60 min or more (L-RCP; n = 19). The patients'
      neurocognitive state was assessed by the revised Wechsler Adult Intelligence
      Scale a few days before operation, at 2-3 weeks and 4-6 months after operation.
      RESULTS: There were no stroke, seizure, and hospital mortality in either group.
      Significant decline between baseline and early scores were seen in three subtests
      (digit span, arithmetic, and picture completion) for S-RCP and four (digit span,
      arithmetic, picture completion, and picture arrangement) for L-RCP. Significant
      decline between baseline and late scores were seen in one subtest (arithmetic)
      for S-RCP, four (digit span, arithmetic, picture completion, and picture
      arrangement) for L-RCP, and one (object assembly) for CABG. The mean change of
      scores for one late test (digit symbol) was significantly lower in S-RCP than in
      CABG. The mean change of scores for three early tests (digit span, vocabulary,
      and picture arrangement) and four late tests (information, digit span, picture
      completion, and picture arrangement) were significantly lower in L-RCP than in
      CABG. Stepwise logistic regression analysis disclosed that, after considering the
      other variables, significant difference in test score changes were observed
      between CABG and L-RCP for two early tests (picture completion and digit symbol)
      as well as for three late tests (digit span, similarities, and picture
      completion). None of test score changes showed significant difference between
      CABG and S-RCP. CONCLUSIONS: The neurocognitive outcome in patients undergoing
      RCP less than 60 min were comparable with patients undergoing CABG without
      circulatory arrest. Prolonged RCP of 60 min or more in patients undergoing
      surgery of the thoracic aorta was associated with postoperative neurocognitive
      impairment.

PMID- 15982594
TI  - Nonlinear heart rate variability in CABG patients and the preconditioning effect.
AB  - OBJECTIVE: Heart rate variability (HRV) is the most frequently used noninvasive
      diagnostic method in the assessment of cardiac autonomic control. The clinical
      relevance of HRV, especially nonlinear HRV in CPB patients has not been well
      studied. Short brief myocardial ischemia has been reported to influence HRV. We
      therefore hypothesis that the protective mechanism of ischemic preconditioning
      (IP) may involve in cardiac autonomic regulation. METHODS: Eighty-six CABG
      patients were randomized into a control and an IP group. The IP patients received
      two periods of 2-min ischemia followed by 3-min reperfusion by aortic cross
      clamped. Holter data were collected in 86 CABG patients before and after surgery.
      Arrhythmias, linear and nonlinear HRV measures were analyzed. RESULTS: All time
      and frequency domain HRV variables as well as nonlinear indexes of HRV, the short
      term (4-11 beats) scaling exponent alpha1, were suppressed significantly after
      surgery in both study groups. The lower pre- and postoperative exponent alpha1
      predict the higher incidence of postoperative AF and worse postoperative outcome.
      The suppressed exponent alpha1 was attenuated in the IP group as compared to
      controls (P = 0.008). No other differences were observed in the changes in linear
      HRV measures between the groups. IP significantly reduced the incidence of
      postoperative arrhythmias and improved postoperative outcome. CONCLUSIONS: The
      present findings show that cardiac autonomic regulation is impaired after CABG.
      Nonlinear HRV exponent alpha1 is a more sensitive measure to predict the
      postoperative outcome in CABG patients. IP alleviates the extreme autonomic
      reactions after surgery, suggesting that cardiac autonomic regulation is involved
      in the IP protective mechanism.

PMID- 15982595
TI  - The association of elevated creatine kinase-myocardial band on mortality after
      coronary artery bypass grafting surgery is time and magnitude limited.
AB  - OBJECTIVE: The joint European Society of Cardiology and American College of
      Cardiology consensus statement on myocardial necrosis after revascularization
      stated that any amount of myocardial necrosis as detected by cardiac enzymes
      should be labeled a myocardial infarct. However, it also stated that more data
      collection is necessary to better interpret the elevation of cardiac enzymes
      after coronary artery bypass grafting. We sought to determine if a single
      postoperative value of creatine kinase-myocardial band could be used as a risk
      factor to help predict mortality after coronary artery bypass surgery. METHODS: A
      retrospective analysis of prospectively collected data on 1161 patients
      undergoing first-time, isolated coronary artery bypass surgery utilizing
      normothermic cardiopulmonary bypass was conducted. Creatine kinase-myocardial
      band was measured the morning after surgery. Binary logistic regression, Cox
      proportional hazard models, and overlapping quintiles were used to illuminate the
      association between creatine kinase-myocardial band elevation and mortality after
      coronary artery bypass surgery. RESULTS: We found a threshold value of creatine
      kinase-myocardial band, 40 ng/mL, above which elevations were associated with
      increased death rates. This association held after adjustment for other factors
      known to contribute to postoperative mortality. However, after 1 year, there was
      no longer a statistically significant higher mortality associated with elevated
      creatinine kinase-myocardial band > 40 ng/mL. CONCLUSION: Elevation of creatine
      kinase-myocardial band the morning after surgery above a threshold 40 ng/mL is
      associated with an increased risk of mortality.

PMID- 15982596
TI  - Antiphospholipid syndrome in cardiac surgery-an underestimated coagulation
      disorder?
AB  - OBJECTIVE: Antiphospholipid syndrome (APS) is a rare coagulation disorder
      associated with recurrent arterial and venous thrombotic events. We analysed our
      experience with five APS patients who underwent cardiac surgery. In three of them
      the diagnosis of APS had been established before surgery, two patients were
      diagnosed after surgery. METHODS: From March 1999 to March 2004 five patients
      with APS underwent cardiac surgery using cardiopulmonary bypass (CPB). We
      retrospectively reviewed their clinical data, operative and postoperative
      courses, and the long-term results. RESULTS: Procedures performed were heart and
      lung transplantation (patient 1), endoventriculoplasty and CABG (patient 2),
      biventricular resection of endoventricular fibrosis and thrombus (patient 3),
      mitral valve repair repair and coronary artery bypass grafting (CABG, patient 4),
      and mitral valve replacement with closure of a patent foramen ovale (patient 5).
      There were three perioperative deaths (patients 1, 2 and 3), two of three
      patients in whom the diagnosis was known before surgery, survived (patients 4 and
      5). In these patients, only half the dose of protamin (patient 4) and no protamin
      at all (patient 5) was applied to reduce the probability of postoperative
      thromboembolic complications. At 1 year follow up, only patient 4 had survived,
      patient 5 had died of the complications of intestinal thromboembolism.
      CONCLUSIONS: Patients with APS undergoing cardiac surgery belong to a high risk
      subgroup. Thus, though rare, APS can be a critical issue in cardiac surgery. Some
      of the cardiac patients with unexplained perioperative thromboembolic
      complications, such as graft occlusion, may turn out to have an undiagnosed APS.

PMID- 15982597
TI  - Outcome of hearts with cold ischemic time greater than 300 minutes. A case
      matched study.
AB  - OBJECTIVE: Expansion of potential donor pool may be facilitated by using cardiac
      allografts with long ischemic time. Early graft failure and potential relation to
      transplant coronary artery disease remains a concern. We sought to evaluate
      outcomes of heart transplantation in recipients of donor allografts with
      prolonged ischemia time. METHODS: The study group consisted of 46 (mean age, 52
      years) consecutive patients at UCLA from 1994 to 2002 that underwent heart
      transplantation with ischemia time > 300 min. This group was compared to a case
      matched control group of 46 (mean age, 51 years) patients identified from our
      database during this time frame for the following factors: UNOS status,
      congenital heart disease diagnosis, preop inotropes, pretransplantation
      creatinine > 1.5 and recipient age. Primary endpoint was mortality and secondary
      were rejection rate and transplant coronary artery disease. Allografts were
      perfused and stored in cold University of Wisconsin solution. RESULTS: Mean donor
      ages of the study and case-matched control group were 34+/-15 and 34+/-14 years,
      respectively. Mean ischemia times were 388 (range, 301-600 min) and 173 (range,
      96-236 min), respectively. The death incidence rate per 100 transplants per year
      was 9% for the study group and 7.4% for the matched group (P = 0.50). Thirty-day
      mortality for the study and case-matched groups were 4.3 and 2.1%, respectively
      (P = 0.9). Late mortality was 16.5 and 18.5%, respectively (P = 0.9). The risk of
      death after 30 days was 7.5 and 5.8%, respectively (P = 0.5, log-rank). One-year
      incidence of acute cellular rejection in the study and case-matched groups were 2
      and 4.5% (P = 0.36), respectively. One-year incidence of transplant coronary
      artery disease in the study and case-matched groups were 4.3 and 5.4%,
      respectively (P = 0.68). CONCLUSIONS: Donor hearts with ischemia time greater
      than 300 min provide comparable early and intermediate outcomes given judicious
      and careful donor and recipient matching and our current techniques of myocardial
      preservation and modified reperfusion.

PMID- 15982599
TI  - Objective assessment of technical skills in cardiac surgery.
AB  - OBJECTIVE: Reduced training time combined with no rigorous assessment for
      technical skills makes it difficult for trainees to monitor their competence. We
      have developed an objective bench-top assessment of technical skills at a level
      commensurate with a junior registrar in cardiac surgery. METHODS: Forty
      cardiothoracic surgeons were recruited for the study, consisting of 12 junior
      trainees (year 1-3), 15 senior trainees (year 4-6) and 13 consultants. The
      assessment consisted of four key tasks on standardised bench-top models: aortic
      root cannulation, vein-graft to aorta anastomosis, vein-graft to Left Anterior
      Descending (LAD) anastomosis and femoral triangle dissection. An expert surgeon
      was present at each station to provide passive assistance and rate performance on
      a validated global rating scale giving rise to a total possible score of 40.
      Three expert surgeons repeated the ratings retrospectively, using blinded video
      recordings. Data analysis employed non-parametric tests. RESULTS: Both live and
      video scores differentiated significantly between performances of all groups of
      surgeons for all four stations (P < 0.01) (median live and video score for LAD;
      Junior 19,17; Senior 29,22; Consultant 36,28). Correlations between live and
      blinded rating were high (r = 0.67-0.84; P < 0.001) as was inter-rater
      reliability between the three expert video raters (alpha = 0.81). CONCLUSIONS:
      The use of bench-top tasks to differentiate between cardiac surgeons of differing
      technical abilities has been validated for the first time. Furthermore, it is
      unnecessary to perform post-hoc video rating to obtain objective data. These
      measures can provide formative feedback for surgeons-in-training and lead to the
      development of a competency-based technical skills curriculum.

PMID- 15982598
TI  - Pre-treatment of donor with 1-deamino-8-d-arginine vasopressin could alleviate
      early failure of porcine xenograft in a cobra venom factor treated canine
      recipient.
AB  - OBJECTIVE: Unlike cardiac or renal xenotransplants, the depletion of complement
      using cobra venom factor (CVF) does not improve pulmonary xenograft survival.
      Several cases suggest that the swine von Willebrand factor (vWF) may play a major
      role in presenting a different pathogenesis of pulmonary xenograft dysfunction
      from other organs. To evaluate the role of vWF and the complement system in
      mediating hyperacute vascular injury of pulmonary xenografts and elucidate
      pathogenesis of the injury, we performed swine-to-canine orthotropic single lung
      xenotransplantation after pre-treatment of 1-deamino-8-d-arginine vasopressin
      (DDAVP) and CVF. METHODS: We set up three groups for lung xenotransplantation:
      group I served as the control group; group II, recipients pre-treated with CVF;
      group III, donors pre-treated with DDAVP (9 mg/kg, 3 days)/recipients pre-treated
      with CVF (60 u/kg). Hemodynamic data, coagulation and complement system
      parameters, and grafted lung pathologies were examined serially for 3h after
      transplantation. RESULTS: DDAVP infusion reduced the vWF content in swine lung
      tissue in vivo (7.7+/-2.4 AU/mg vs 16.0+/-5.6 AU/mg, P < 0.0001). Infusion of CVF
      24 h prior to transplantation effectively depleted the recipient's serum C3 and
      complement hemolytic activity below the detectable range. Regardless of the use
      of CVF, both groups I and II transplanted with unmodified grafts showed an
      immediate drop in leukocytes and platelet counts after transplantation. However,
      in group III, in recipients transplanted with DDAVP pre-treated swine lung, the
      platelet count did not decrease after transplantation (P = 0.0295). The decrease
      of plasma antithrombin and fibrinogen tended to be attenuated in group III. Light
      microscopic examination revealed extensive vascular thromboses in both capillary
      and larger vessels, as well as early pulmonary parenchymal damage in groups I and
      II, but were rarely observed in group III. CONCLUSIONS: Complement inhibition
      alone was not enough to alleviate intravascular thrombosis, the main pathology in
      pulmonary xenotransplantation. Pre-infusion of DDAVP to the donor animal was
      effective in preventing platelet sequestration and attenuated intravascular
      thrombosis. It is suggested that the strategies targeting vWF would be promising
      for successful pulmonary xenotransplantation.

PMID- 15982600
TI  - Giant saphenous vein graft aneurysm.

PMID- 15982601
TI  - Early experience with robotic aortic valve replacement.
AB  - We report our initial experience with aortic valve replacement using robotic
      assistance. All procedures were performed with peripheral cardiopulmonary bypass,
      transthoracic aortic cross-clamp, and antegrade cold crystalloid cardioplegia.
      One or two ports and a 5-cm intercostal incision in the right chest were used for
      access. All patients had aortic valve replacement performed robotically. Between
      February and September 2004, five patients underwent robotic aortic valve
      replacement. The mean age was 59 years (range 35-82 years). There were no
      incisional conversions, death, stokes, or reoperations for bleeding. Overall mean
      study times were as follows: procedure, 231.2 min (range 180-315 min);
      cardiopulmonary bypass, 121.5 min (range 83-173 min), and cross-clamp, 98.2 min
      (range 67-140 min). One patient developed postoperative pneumonia. Aortic valve
      replacement can be successfully performed with the da Vinci robotic system.

PMID- 15982602
TI  - Use of the Arndt wire-guided endobronchial blocker via nasal for one-lung
      ventilation in patient with anticipated restricted mouth opening for
      esophagectomy.
AB  - Functional separation of the lungs may be accomplished by several methods.
      Patient with restricted mouth opening has limited options for one-lung
      ventilation. We report the use of wire-guided endobronchial blockade, a new tool
      for achieving one-lung ventilation in a patient with restricted mouth opening
      requiring nasotracheal, fiberoptic intubation for esophagectomy and
      reconstruction with gastric tube substitution.

PMID- 15982603
TI  - Postpneumonectomy esophageal compression: an unusual complication.
AB  - We report a case of postpneumonectomy esophageal compression with a complaint of
      dysphagia. In addition to the bronchial compression seen in postpneumonectomy
      syndrome, other anatomic structures, such as the esophagus, can also be affected
      by the extreme mediastinal shifting, and possibly be corrected by placement of
      prosthetic devices into the ipsilateral hemithorax, or with a stent placement.

PMID- 15982604
TI  - Donor infection: an opinion on lung donor utilization.

PMID- 15982605
TI  - Conversion from cyclosporine microemulsion to tacrolimus-based immunoprophylaxis
      improves cholesterol profile in heart transplant recipients with treated but
      persistent dyslipidemia: the Canadian multicentre randomized trial of tacrolimus
      vs cyclosporine microemulsion.
AB  - BACKGROUND: Tacrolimus improves lipid profile in renal and liver transplant
      recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to
      tacrolimus (Prograf) in a large randomized study of stable heart transplant
      recipients with treated but persistent mild dyslipidemia is reported. METHODS:
      One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion
      treated heart transplant recipients with low-density lipoprotein cholesterol >2.5
      mmol/liter and/or a total cholesterol/high-density lipoprotein cholesterol ratio
      >4 were recruited for the study. Complete lipid profile was assessed before
      (baseline) and after 6 months of treatment with either cyclosporine microemulsion
      maintenance (n=64) or tacrolimus conversion (n=65). RESULTS: At 6 months,
      tacrolimus-converted patients exhibited a greater decrease in total cholesterol
      (from 5.51 +/- 0.16 to 4.88 +/- 1.22 mmol/liter [tacrolimus], vs 5.61 +/- 1.36 to
      5.38 +/- 0.87 mmol/liter [cyclosporine]; p = 0.0078). This decrease in
      cholesterol was caused largely by a decrease in low-density lipoprotein
      cholesterol (-0.41 +/- 0.54 [tacrolimus] vs -0.13 +/- 0.55 [cyclosporine];
      p=0.0018). There were no changes in high-density lipoprotein cholesterol and
      triglyceride levels, but apolipoprotein B therapy was reduced in tacrolimus
      converted vs cyclosporine-maintained patients (p=0.0003). By 6 months, 23.7% of
      tacrolimus- vs 6.7% of cyclosporine-treated patients met the target lipid levels
      for high-risk patients (p=0.0094). Conversion from cyclosporine to tacrolimus
      resulted in decreases in blood urea nitrogen, creatinine, and uric acid without
      any changes in glucose, HbA(1C), and insulin levels. CONCLUSIONS: Conversion from
      cyclosporine microemulsion- to tacrolimus-based immunoprophylaxis resulted in
      decreased cholesterol, apolipoprotein B, urea, creatinine, and uric acid without
      any clinically evident perturbation of glucose metabolism in stable heart
      transplant recipients with treated but persistent mild dyslipidemia.

PMID- 15982606
TI  - Special report from the heart transplant candidate registry committee in Japan.
AB  - BACKGROUND: Heart transplantation had been withheld for long time in Japan. In
      October 1997 organ transplant legislation was implemented and the heart
      transplantation program began. In February 1999 the first heart transplantation
      was performed. Since then a total of 17 successful transplantations have been
      done. METHODS: This report describes the profiles of heart transplant applicants
      presented to the Heart Transplant Candidate Registry Committee of the Japanese
      Circulation Society from 1997 to 2003. RESULTS: Two hundred eighty-four
      applications were submitted to the Committee for the evaluation. All applicants
      were <60 years of age (mean 32 years). Ninety-two percent of these applicants had
      chronic severe heart failure with New York Heart Association (NYHA) Class III or
      IV status. Etiology of heart failure was dilated cardiomyopathy in 80% of
      applicants, although only 6% had ischemic heart disease, which is in notable
      contrast to Western countries. Most applicants died while waiting for
      transplantation and thus only 17 patients underwent heart transplantation, with
      an average waiting time of 514 days. Recipient prognosis was satisfactory with a
      survival rate of 100%. CONCLUSION: In Japan, heart transplantation is not yet
      considered a viable treatment option for severe heart failure.

PMID- 15982607
TI  - Stability of right and left ventricular ejection fractions and volumes after
      heart transplantation.
AB  - BACKGROUND: The long-term stability of right ventricular (RV) and left
      ventricular (LV) volume and function after heart transplantation has not been
      well characterized. Accordingly, the objective of this study was to assess time-
      and rejection-dependent changes in RV and LV function and volume after cardiac
      transplantation by means of a recently validated 3-dimensional tomographic
      equilibrium radionuclide ventriculography approach. METHODS: A total of 71
      consecutive patients (age, mean +/- SD, 57 +/- 12 years; 62 men; 9 women) were
      studied 5 +/- 4 years (range 1--16 years) after heart transplantation. The mean
      frequency of >Grade 2 rejection was 1.7 +/- 1.8 episodes (range 0--7 episodes).
      RV and LV ejection fraction (EF) and end-diastolic volume (EDV) in transplant
      patients were compared with data from 34 subjects at low likelihood for coronary
      artery disease. RESULTS: No significant differences in RV or LV EF or EDV
      compared with controls were observed (RV EF=54 +/- 9 vs 53 +/- 9; RV EDV [ml]=109
      +/- 35 vs 120 +/- 32; LV EF=72 +/- 8 vs 73 +/- 9; and LV EDV [ml]=108 +/- 28 vs
      98 +/- 20 for controls and patients with transplants, respectively; p=NS for all
      comparisons). There was no significant effect on RV or LV EF or volumes with
      rejection, or with time after transplantation. CONCLUSIONS: RV as well as LV EF
      and EDV are stable more than 1 year after heart transplantation for up to 16
      years. Thus, changes in EF or EDV in the transplanted heart are abnormal and
      should prompt a clinical evaluation.

PMID- 15982608
TI  - Features of the metabolic syndrome of "hypertriglyceridemic waist" and transplant
      coronary artery disease.
AB  - BACKGROUND: This study evaluated the prevalence of the atherogenic metabolic
      triad and the hypothesis that waist circumference and fasting triglyceride
      concentrations could be used as screening tools for identification of the
      atherogenic metabolic triad in a population of heart transplant men. It also
      evaluated the relationship between the atherogenic metabolic triad and coronary
      artery disease (CAD). METHODS: In the study group of 83 consecutive male heart
      transplant patients having their routine annual coronarography, 23 patients (28%)
      were characterized by the atherogenic metabolic triad defined by the presence of
      elevated fasting insulin and apolipoprotein B concentrations and by small low
      density lipoprotein (LDL) particles. RESULTS: Seventy-seven per cent of patients
      with waist circumference values >/= 90 cm and with elevated triglyceride levels
      (>/=2.0 mmol/liter) were characterized by this atherogenic metabolic triad.
      Patients with the atherogenic metabolic triad were at markedly increased risk of
      CAD (odds ratio of 25.3, 95% CI: 1.11-577.3, p < 0.04) compared to heart
      transplant patients without the atherogenic metabolic triad. CONCLUSIONS: About
      30% of heart transplant patients showed the features of the atherogenic metabolic
      triad. Measurement and interpretation of waist circumference and fasting
      triglycerides could be used among heart transplant patients to early identify men
      characterized by the presence of elevated fasting insulin and apolipoprotein B
      concentrations and small LDL particles. The presence of the atherogenic metabolic
      triad identified patients at high risk of CAD even in the heart transplant
      population.

PMID- 15982609
TI  - Early inhibition of caspase-3 activity lessens the development of graft coronary
      artery disease.
AB  - BACKGROUND: The role of apoptosis in the development of graft coronary artery
      disease (GCAD) is poorly understood. We have previously shown that early
      overexpression of the anti-apoptotic protein Bcl-2 lessens the development of
      GCAD. We hypothesized that early inhibition of apoptosis with a caspase-3
      inhibitor would also lessen the development of GCAD. METHODS: Heterotopic heart
      transplantation was performed in 4 groups of rats. Donor hearts were pretreated
      with 50 microg DEVD-CHO, a cell-permeable caspase-3 inhibitor, or vehicle.
      Recipient animals were pretreated with 1.7 mg/kg intraperitoneal DEVD-CHO or
      vehicle. Animals were treated with 7.5 mg/kg/d cyclosporine for 10 days to
      prevent acute rejection. On post-operative day 90, the animals were sacrificed
      and the transplanted hearts were assessed morphometrically for evidence of GCAD.
      RESULTS: At 90 days, intimal proliferation was significantly higher in vehicle
      treated animals than in inhibitor treated animals. Moreover, the percentage of
      vessels with high-grade occlusion (>50%) was also lower in inhibitor treated
      animals. CONCLUSIONS: Early inhibition of caspase-3 activity with cell-permeable
      DEVD-CHO lessens the development of GCAD. Caspase-3 inhibition may be a useful
      strategy for prevention of GCAD in clinical transplantation.

PMID- 15982610
TI  - Peripheral expansion of circulating T-helper 1 cells predicts coronary
      endothelial dysfunction after cardiac transplantation.
AB  - OBJECTIVE: We sought to assess the importance of Th1 cells for the development of
      cardiac allograft vasculopathy. BACKGROUND: Despite improvements in
      immunosuppressive regimens, chronic rejection still represents one of the leading
      causes of death beyond the first year after heart transplantation. Chronic
      rejection is characterized by the development of transplant vasculopathy. The
      exact mechanisms initiating and promoting this form of arteriosclerosis in the
      human setting remain unclear. METHODS: In order to assess the role of T
      lymphocytes we characterized differentiated T-cell subsets in 32 transplant
      recipients early after transplantation using RT-PCR, flow cytometry and
      immunhistochemistry and matched these findings with endothelial function testing
      as an early clinical indicator of transplant vasculopathy. RESULTS: Allograft
      endothelial dysfunction (ED) was defined as a compromised coronary flow reserve
      to acetylcholine (CFVR<2 in 8 of 32 transplant recipients). In these patients,
      mRNA transcript levels for the T-helper (Th)1 signature cytokines interferon
      (INF)-gamma (p<0.0001) and interleukin (IL)-2 (p<0.005) and STAT4 (Th1
      transcription factor, p<0,05) were significantly higher than in the remaining 24
      patients with normal endothelial function. This correlated with a significant
      increase in circulating CD3(+)/IFN-gamma(+)-T-cells (28.6 +/- 4.4% vs 8.7 +/-
      5.6%; p<0.0001). In contrast, transcript levels for the Th2 signature cytokines
      (IL-4, IL-10) and STAT6 (Th2 transcription factor) did not differ significantly
      between the two groups. CONCLUSIONS: Peripheral expansion of circulating Th1 but
      not Th2 cells predicts coronary ED after cardiac transplantation. Therefore,
      quantification of circulating T cells might be a diagnostic tool to predict
      development of ED in patients after heart transplantation.

PMID- 15982611
TI  - Rejection severity directly correlates with myocyte apoptosis in pig-to-baboon
      cardiac xenotransplantation.
AB  - BACKGROUND: The process by which cardiac myocytes die during xenograft rejection
      is incompletely understood. The presence of cardiac myocyte apoptosis in
      discordant xenotransplant models has been noted, yet no investigators have
      examined whether a relationship between myocyte apoptosis and rejection severity
      exists. Thus, we chose to further investigate this observation. METHODS: Eight
      explanted pig-to-baboon cardiac grafts with varying severities of rejection, as
      determined by hematoxylin and eosin histology, were examined for apoptosis by
      transmission electron microscopy (TEM) and TUNEL (terminal deoxynucleotide
      transferase-mediated digoxigenin-dUTP nick-end labeling) immunohistochemistry. In
      addition, Western blot analysis for the cleavage of the apoptosis regulatory
      proteins pro-caspase 8 and 3 was performed. RESULTS: Transmission electron
      microscopy revealed that a severely rejected graft displayed widespread
      condensation of nuclear chromatin, which is a characteristic morphologic feature
      of apoptosis. TUNEL staining verified this observation and allowed for the
      quantification of myocyte apoptosis in each graft. Subsequent linear regression
      analysis of the extent of myocyte apoptosis and rejection severity revealed a
      direct correlation (R(2)=0.757, p=0.005). In addition, Western blot analysis
      demonstrated that myocyte apoptosis involves the cleavage of pro-caspase 8 and 3.
      CONCLUSIONS: Myocyte death in rejecting pig-to-baboon cardiac xenografts occurs
      through an apoptotic pathway and directly correlates with the severity of graft
      rejection. Further studies aimed at elucidating the apoptotic stimulus are
      therefore warranted. Moreover, our data suggest that antiapoptotic strategies may
      be of benefit in the treatment of xenograft rejection.

PMID- 15982612
TI  - The 6-minute walk test does not reliably detect changes in functional capacity of
      patients awaiting cardiac transplantation.
AB  - BACKGROUND: Peak oxygen consumption (Vo(2)peak) is a strong independent predictor
      of prognosis in patients with severe chronic heart failure (CHF) and is used to
      guide optimal timing of transplantation. However, its assessment is relatively
      expensive and time-consuming and requires sophisticated equipment and highly
      trained personnel. The purpose of this study was to determine whether changes in
      6-minute walk test (6WT) distance, a simple, inexpensive potential alternative
      measure of functional capacity, can predict changes in Vo(2)peak in patients with
      severe CHF. METHODS: Sixteen subjects (ejection fraction 23+/-2%, Vo(2)peak
      16.2+/-1.1 ml kg (-1)min(-1)) underwent repeated 6WT and Vo(2)peak assessments
      that included familiarization and 4 serial measures, 6 weeks apart (baseline and
      at Weeks 6, 12 and 18). Analysis compared baseline performance with each
      subsequent testing occasion. RESULTS: At baseline, mean (+/-SE) VO(2)peak was
      16.3+/-1.1 ml kg(-1) min(-1) and 6WT distance was 458+/-21 m. 6WT and Vo(2)peak
      were strongly correlated at all timepoints (average r=0.82; all p<0.05). However,
      mixed model analysis, assessing the capacity of the changes seen in 6WT to
      predict changes in Vo(2)peak, showed no statistical significance (F=0.11;
      p=0.74). CONCLUSIONS: The 6WT is commonly used to assess functional capacity in
      patients with heart failure. This study demonstrates that, despite a strong cross
      sectional correlation with Vo(2)peak, changes in the 6WT are not a reliable
      predictor of changes in Vo(2)peak within patients. Therefore, the 6WT has limited
      utility as a serial measure to assess changes in the clinical status of patients
      with severe heart failure.

PMID- 15982614
TI  - Equivalence of flow velocities through bilateral pulmonary vein anastomoses in
      bilateral living-donor lobar lung transplantation.
AB  - BACKGROUND: Intraoperative transesophageal echocardiography (TEE) during lung
      transplantation is useful for monitoring cardiac condition and pulmonary vascular
      anastomoses to detect vascular complications, but the parameters for evaluation
      by TEE during lung transplantation have not been established. METHODS: We
      performed intraoperative TEE on 17 patients during living-donor lobar lung
      transplantation (LDLLT) and investigated the usefulness of measurement of peak
      flow velocities through bilateral pulmonary vein (PV) anastomoses and evaluation
      of the equivalence. RESULTS: The peak flow velocities through bilateral PV
      anastomoses were almost equivalent in 14 patients without complications and were
      not equivalent in 3 patients with complications such as vascular stenosis and
      peripheral atelectasis. CONCLUSIONS: The flow velocities through the bilateral PV
      anastomoses are shown to be nearly equivalent during bilateral LDLLT, and the
      equivalence may be one factor for predicting the success of LDLLT.

PMID- 15982613
TI  - Intracellular monocyte cytokine production and CD 14 expression are up-regulated
      in severe vs mild chronic heart failure.
AB  - BACKGROUND: The role of circulating monocytes in the process of low-grade
      inflammation, characteristic of chronic heart failure (CHF), has recently been
      questioned. Lipopolysaccharide (LPS) desensitization has been proposed to mediate
      reduced monocyte cytokine elaboration in patients with severe CHF. METHODS:
      Intracellular monocyte production of interleukin-1 beta (IL-1 beta), interleukin
      6 (IL-6) and tumor necrosis factor (TNF)-alpha, and monocyte CD 14 expression
      were measured flow-cytometrically without and after 8-hour LPS stimulation in 46
      patients with CHF and in a healthy control group. RESULTS: Basal cytokine
      concentrations were similar for the control and the mild CHF groups (New York
      Heart Association [NYHA] Class I or II). After LPS stimulation, IL-6 (p=0.002)
      and TNF-alpha levels (p=0.001) were lower in the latter group, whereas IL-1 beta
      production was comparable. For the moderate-severe CHF patients, unstimulated IL
      1 beta (p=0.04) was higher, whereas IL-6 (p=0.2) and TNF-alpha (p=0.1) levels
      were not different from the controls. Measurement of LPS-stimulated cytokine
      production showed no differences between the control group and patients with
      moderate-severe CHF (all p= 0.5). Upon comparing mild vs moderate-severe CHF
      patients, higher levels of unstimulated cytokine production (IL-1 beta, p=0.002;
      IL-6, p=0.01; TNF-alpha, p=0.003), stimulated IL-1 beta (p=0.002) and IL-6
      (p=0.008) were found in the latter patients. CD 14 expression in the moderate
      severe CHF group was higher than in the mild-CHF group (p = 0.03) and was
      strongly related to stimulated IL-1 beta (r=0.62, p<0.0001), IL-6 (r=0.56,
      p=0.0002) and TNF-alpha (r=0.41, p=0.006) production. CONCLUSIONS: CD 14
      expression and monocyte cytokine production, both unstimulated and after LPS
      stimulation, are increased in moderate-severe CHF when compared with mild CHF.
      These data suggest that circulating monocytes, possibly via increased CD 14
      expression, may play a significant role in the immunologic dysbalance observed in
      advanced CHF.

PMID- 15982615
TI  - Lung transplantation outcome in cystic fibrosis patients with previous
      pneumothorax.
AB  - BACKGROUND: High perioperative mortality that results from hemorrhage from
      pleural adhesions was reported in the early experience of heart-lung
      transplantation. This led to previous pleural procedures becoming a
      relative/absolute contraindication to transplantation in some centers, despite
      the advent of bilateral lung transplantation. Has this lead to a more
      conservative approach to pneumothorax management in patients with cystic fibrosis
      (CF)? And what is the effect of previous pleural procedures on surgical outcome
      of lung transplantation? METHODS: We reviewed 3 groups of patients transplanted
      at this center from 1989 to 2002, matched for year of lung transplantation. Group
      A comprised 16 patients with CF with a history of previous pneumothorax with or
      without pleural procedure. Group B comprised 16 patients with CF with no history
      of pneumothorax. Group C comprised 16 noninflammatory/nonbronchiectatic patients
      with no history of pneumothorax. Measured outcomes included blood products
      provided intraoperatively; operation and cardiopulmonary bypass times;
      postoperative hemorrhage; times to extubation, discharge from the intensive care
      unit and hospital discharge; forced expiratory volume at 1 second at 6 months; 30
      day mortality; pleural adhesions graded descriptively; and previous pneumothorax
      management (Group A only). There were 35 pneumothorax episodes in the 16 patients
      in Group A. Nine episodes were managed with observation alone. Nine patients
      required invasive management, 25 chest drains were placed, 3 patients received
      medical pleurodesis, and 2 underwent thoracic surgical intervention. RESULTS: No
      significant difference was observed between the 3 groups regarding blood products
      intraoperatively or duration of procedure. Pleural adhesions found at operation
      were significantly more in Group A, with dense adhesions found only in Group A
      (p<0.05). Group C was significantly more likely to be free from adhesions, with
      13 patients clear (p<0.01 Group C vs Group A, Group C vs Group B). No
      statistically significant difference was found in the other measured parameters.
      CONCLUSIONS: Pneumothorax is treated conservatively in a potential lung
      transplant population. Patients with CF and previous pneumothorax with or without
      pleural procedures undergoing lung transplantation have dense pleural adhesions;
      however, this does not affect surgical outcome significantly. Patients with
      emphysema, fibrosing alveolitis, or obliterative bronchiolitis were significantly
      more likely to be free of pleural adhesions, suggesting that the
      inflammatory/chronic infective component of CF independently contributes to the
      increased pleural adhesions. Previous pleural procedures for pneumothorax should
      not be considered a contraindication in the assessment of suitability for lung
      transplantation.

PMID- 15982616
TI  - The utility of cytopathology testing in lung transplant recipients.
AB  - BACKGROUND: Lung transplant recipients routinely undergo bronchoscopy, during
      which bronchoalveolar lavage (BAL) fluid and transbronchial biopsies are usually
      obtained. These specimens are typically sent for microbiology, histopathology and
      cytopathology testing. Cytopathology testing is expensive, and its diagnostic
      value is questionable. We hypothesized that cytopathology specimens have no
      additional diagnostic yield beyond that of microbiology and histopathology
      testing in the routine care of our lung transplant patients. METHODS: We reviewed
      all bronchoscopies performed on a cohort of patients who underwent lung
      transplantation between February 1999 and August 2002 at our institution.
      Demographic data, immunosuppressive therapy and the incidence of opportunistic
      infections in this cohort of 65 patients were reviewed. To ascertain the
      diagnostic value of cytopathology testing, microbiology and histopathology
      results from bronchoalveolar lavage and transbronchial biopsy tests were compared
      with cytopathology results. RESULTS: Three hundred sixty-six bronchoscopies were
      reviewed. Microbiologic and histopathology identified 51 cytomegalovirus-, 157
      fungus- and 13 mycobacteria-positive specimens as well as respiratory syncitial
      virus, influenza A and B, enterovirus, actinomyces, Nocardia and mycoplasma.
      Cytopathology of BAL fluid identified only 3 cytomegalovirus- and 13 fungus
      positive specimens. The only unique diagnoses made by cytopathology were 1 case
      of Aspergillus and 1 unidentifiable fungal element. CONCLUSIONS: We conclude that
      routine cytopathology testing has little additive diagnostic value in
      bronchoscopic specimens from lung transplant recipients. Cytopathology results
      did not alter patient management in any of our 366 cases. Centers should consider
      discontinuing routine use of cytopathology testing of BAL fluid for surveillance
      or clinically indicated bronchoscopy, because the yield of this expensive test is
      extremely low in the setting of lung transplantation.

PMID- 15982617
TI  - Interleukin-17--induced interleukin-8 release in human airway smooth muscle
      cells: role for mitogen-activated kinases and nuclear factor-kappaB.
AB  - BACKGROUND: It has recently become clear that interleukin (IL)-8 plays a role in
      chronic neutrophilic inflammatory disorders, such as chronic rejection after lung
      transplantation. We have shown that IL-17--stimulated human airway smooth muscle
      cells (HASMC) are able to produce IL-8. The aim of this study was to determine
      whether p38 mitogen-activated protein kinase (MAPK), c-Jun amino-terminal kinase
      (JNK), p42/p44 extracellular signal-related kinase (ERK) and nuclear factor
      kappaB (NF-kappaB) are involved in IL-17--induced IL-8 production in HASMC in
      vitro. METHODS: We used human airway smooth muscle cells in culture. Western
      blotting was done to obtain data regarding activation of MAPK. Furthermore, we
      used specific inhibitors of MAPK to investigate their involvement in IL-17-
      induced IL-8 release, which was measured by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Western blotting clearly demonstrated that p38 MAPK, JNK and
      p42/p44 ERK were activated by IL-17 in HASMC. Using SB203580, a specific
      inhibitor of p38 MAPK, we detected a concentration-dependent inhibition of IL-17-
      induced IL-8 production with a maximal decrease of 63 +/- 5% (n=8, p<0.01).
      Curcumin, a specific inhibitor of JNK, also concentration-dependently reduced IL
      17--induced IL-8 production, with a maximal decrease of 82+/-4% (n=8, p<0.01).
      U0126, a specific inhibitor of p42/p44 ERK, induced a maximal decrease of 84+/-5%
      (n=8, p<0.001). Pyrrolydine dithiocarbamate (PDTC), an inhibitor of NF-kappaB,
      caused a 70+/-5% (n=8, p<0.01) decrease in IL-17--induced IL-8 production.
      CONCLUSIONS: We found that IL-17 induces activation of p38MAPK, JNK and
      p42/p44ERK in HASMC. We also found that p38MAPK, JNK, p42/p44 ERK and NF-kappaB
      play an important role in IL-17--induced IL-8 production in HASMC in vitro. This
      may open up new opportunities for further treatment of this disease.

PMID- 15982618
TI  - Integrity of airway epithelium is essential against obliterative airway disease
      in transplanted rat tracheas.
AB  - BACKGROUND: The pathogenesis of obliterative bronchiolitis after lung
      transplantation requires further elucidation. In this study we used rat trachea
      transplantation to examine the role of epithelium in the progression of
      obliterative airway disease. METHODS: Normal and denuded (i.e., epithelium
      removed) trachea grafts from Lewis (LEW) and Brown Norway (BN) rats were
      transplanted sub-cutaneously into LEW rats. Viable trachea epithelial cells (to
      recover epithelium) were seeded into the lumen of some of the denuded tracheas.
      Grafts were removed at different time-points between 2 days and 8 weeks after
      transplantation. Histologic analysis was performed to evaluate cellular
      infiltration of inflammatory cells, loss of epithelium, and obliteration of
      trachea lumen. RESULTS: Obliteration was found to occur in trachea transplants
      after loss of epithelium, caused by rejection in allografts or by enzymatic
      denudation in isografts. In these situations, fibroblasts started to proliferate
      and migrate into the lumen in the second week after transplantation. Obliteration
      could be prevented when epithelial integrity was restored by seeding epithelial
      cells; no obliteration occurred when denuded trachea isografts were seeded with
      epithelial cells, whereas non-seeded denuded tracheas were obliterated at Day 6
      after transplantation. CONCLUSIONS: We conclude that integrity of airway
      epithelium is essential for rat trachea transplants to be safeguarded from
      obliterative airway disease. For clinical lung transplantation the results of our
      study suggest that protection of the integrity of airway epithelium may be
      important in preventing the development of obliterative bronchiolitis.

PMID- 15982619
TI  - Blood pressure after cardiac transplantation in childhood.
AB  - BACKGROUND: There has been little formal study of blood pressure in children
      after cardiac transplantation. METHODS: Twenty-four-hour and clinical blood
      pressure (BP) were measured in 28 children (>6 months after transplantation) and
      compared with a large amount of normal data. RESULTS: Conventional (clinical)
      systolic BP (SBP) was elevated in 9 (32.1%) of 28 (95% confidence interval [CI]
      15.8 to 52.3), and conventional diastolic BP (DBP) was elevated in 5 (17.8%) of
      28 (95% CI 6.0 to 36.8). Mean 24-hour BP was >97.5 percentile in 2 (7.7%) of 26
      (95% CI 0.9 to 25.1) for SBP and in 7 (28.0%) of 25 (95% CI 12.1 to 49.4) for
      DBP. In comparison with the control population, mean nighttime SBP was 8.9 mm Hg
      higher in the transplanted group (95% CI 4.8 to 13.1), but daytime and mean 24
      hour SBP were similar. Mean day, night, and 24-hour DBP was significantly higher
      in the transplanted patients. The nighttime decrease in BP was significantly less
      than controls for SBP, but not for DBP. Conventional BP measurement was poorly
      predictive of 24-hour BP. There was a significant association between mean 24
      hour SBP and interventricular septal thickness (r(2)=0.35; p=0.01). DBP was not
      associated with interventricular septal thickness (r(2)=0.07; p=0.20) but was
      significantly correlated with the time since transplantation (r=0.42; p=0.03 for
      conventional DBP and r=0.43; p=0.04 for 24-hour DBP). CONCLUSIONS: The elevation
      of DBP in children after cardiac transplantation is unexplained. The elevation in
      nighttime SBP has possible important therapeutic implications and is not
      predicted by conventional (clinical) BP measurement.

PMID- 15982621
TI  - Paradoxical toxicity of cardioplegic compounds on ischemic cardiomyocyte using
      optimal design strategy.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of major components
      of cardioplegic solutions on myocardial tissue submitted to prolonged cold
      ischemia. METHODS: Our methodology was based on the simultaneous testing in the
      same series of experiments of many compounds (19 in number), which were included
      in the composition of 20 established solutions. All the experiments were
      performed by a matricial-predefined protocol that allows the evaluation of the
      protective or toxic effects of each of these 19 compounds. Pig hearts were
      removed and left ventricular myocardiums were cut into 320 pieces. For each
      solution tested, 8 pieces of myocardial tissue were incubated at 4 degrees C for
      24 hours and 8 other pieces were incubated for 72 hours. At the end of incubation
      period, tissue injury was assessed by measuring the leakage of myocardial
      enzymes(glutamic-oxaloacetic transaminase, lactate dehydrogenase, creatine
      phosphokinase) into the incubation medium. Initially, the effects of each
      solution were evaluated, and then a mathematical analysis was performed and the
      effects of each compound deduced. RESULTS: After the 24-hour incubation period,
      pyruvate (5 mmol/liter), polyethylene glycol (5 mmol/liter), Ala-Gln (20
      mmol/liter), and reduced glutathione (3 mmol/liter) showed toxic effects, whereas
      ethanol (1%) and calcium chloride (2 mmol/liter) seemed to be protective. After
      72 hours' incubation, similar data were obtained; dextran 70 (0.57 mmol/liter)
      was also found to be deleterious. CONCLUSIONS: The results revealed surprising
      myocardial toxicity (enzymatic release) from components included in cardioplegic
      solutions. Some components would induce metabolic activation during prolonged
      hypothermic ischemia, which may be inappropriated and which may perhaps
      exacerbate damages by increasing membrane ruptures. This concept confirms
      eventual discrepant effects of preservative compounds on cardiomyocyte membrane
      during deep hypothermia, according to the metabolic state of the cell.

PMID- 15982620
TI  - Pyruvate-modified perfadex improves lung function after long-term hypothermic
      storage.
AB  - BACKGROUND: Lungs harvested for transplantation are stored while inflated with
      oxygen, which can serve to support oxidative metabolism. However, strategies
      aimed at increasing graft metabolism during storage have received little
      attention. In this study, we added pyruvate to the preservation solution Perfadex
      and measured the effects on oxidative metabolism and reperfusion lung function.
      METHODS: Rat lungs were stored for 6 and 24 hours in low-potassium dextran
      solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U
      (13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or
      both (combined). Oxidation of exogenous substrates was measured as the
      incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic
      resonance spectroscopy. Additional groups of lungs with each substrate
      modification were preserved for 6 or 24 hours and then reperfused. RESULTS:
      Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex
      group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast,
      enrichment was significantly increased in both the pyruvate group (50% and 59%,
      respectively) and combined group (39% and 54%, respectively) compared with the
      Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all
      groups. All lungs stored for 24 hours exhibited inferior lung function, but
      oxygenation, pulmonary artery pressures, and airway pressures in the combined
      group were significantly improved compared with the Perfadex group (p<0.05).
      CONCLUSIONS: Preservation solution substrate composition influences graft
      metabolism during storage. The addition of pyruvate to Perfadex increases
      metabolism during storage and improves reperfusion lung function.

PMID- 15982622
TI  - Effects of crystalloid, blood and Celsior solutions on porcine coronary
      endothelial function after heart transplantation.
AB  - BACKGROUND: Coronary endothelial dysfunction occurs early after heart
      transplantation and predicts the development of cardiac allograft vasculopathy.
      Cardioplegic solutions may cause endothelial injury. The present study aimed to
      assess the effects of cardioplegic solutions (crystalloid, blood and Celsior)
      used at the time of graft harvesting on endothelial function and intimal
      hyperplasia 1 month after heart transplantation. METHODS: A porcine heterotopic
      heart transplantation model was used. Three experimental groups were studied:
      crystalloid, blood and Celsior solutions were used for induction of cardiac
      arrest. Epicardial coronary arteries of native and allograft hearts were studied
      1 month after transplantation in organ chambers. Endothelium-dependent
      relaxations to serotonin, bradykinin and calcium ionophore were assessed.
      Coronary neointimal proliferation was evaluated using histomorphometric studies.
      RESULTS: Endothelium-dependent relaxations to serotonin and to calcium ionophore
      were significantly decreased in all 3 experimental groups vs controls (p<0.05).
      Endothelium-dependent relaxations to bradykinin were significantly reduced in the
      crystalloid group compared with the Celsior and blood groups and controls
      (p<0.05). There was a significantly lower rate of severe intimal hyperplasia in
      the Celsior group compared to the crystalloid and blood groups (p<0.05).
      CONCLUSION: Celsior cardioplegic solution represents the solution of choice in
      terms of preservation of endothelial function and lower incidence of severe
      coronary intimal hyperplasia following transplantation compared with crystalloid
      and blood cardioplegia solutions. These early results could translate into a
      reduction of the long-term incidence of cardiac allograft vasculopathy and
      improve graft survival.

PMID- 15982623
TI  - Stable myocardial function and endocrine dysfunction during experimental brain
      death.
AB  - BACKGROUND: The origin of cardiac impairment during brain death (BD) is
      controversial. Using a pig experimental model we sought to assess hormonal
      changes during the first stage of brain death and how these changes contribute to
      hemodynamic alteration and myocardial dysfunction. METHODS: Twenty-two pigs were
      randomized into 2 groups: a control (C) group and a BD group. BD was induced by
      sub-dural inflation of a balloon catheter. Micromanometers and ultrasonic flow
      probes were placed on the myocardium to measure cardiovascular parameters. Blood
      samples and hemodynamic parameters were analyzed before and after induction of
      BD. RESULTS: A biphasic release of catecholamines was observed, with an initial
      peak occurring 1 minute after BD induction, followed by a second peak at 60
      minutes. Similarly, a biphasic evolution of dP/dt(max) and systolic blood
      pressure (SBP) was observed at BD, in parallel with catecholamine evolution. In
      the BD group, both cortisol and aldosterone decreased progressively over time.
      Circulating triiodothyronine (T3), levothyroxine (T4), prolactin and melatonin
      concentrations were similar to those of the control group. The difference in
      arteriovenous (AV) lactate level in arterial and coronary sinus blood was not
      significantly different between the 2 groups, suggesting an absence of myocardial
      ischemia. Furthermore, myocardial contractility was not altered during the 3
      hours of BD. CONCLUSIONS: During the initial period after induction of brain
      death, cerebral and thyroid hormones remained stable while cortico- and medullo
      surrenal hormones varied significantly. We suggest that suprarenal gland
      impairment is among the first events occurring during brain death. Paradoxically,
      hemodynamic parameters and myocardial function were not found to be altered.

PMID- 15982624
TI  - Impact of donor serum sodium levels on outcome after heart transplantation.
AB  - We investigated the impact of elevated donor serum sodium levels on outcome after
      heart transplantation in 336 consecutive heart transplantations. Mean donor serum
      sodium was 148.2+/-10.2 mmol/liter (range 116 to 180 mmol/liter). Recipients were
      divided into 4 groups with serum sodium levels of 141, 147 and 155 mmol/liter,
      resulting in sodium levels of: 133+/-6.1 mmol/liter for Quartile A; 144+/-4.2
      mmol/liter for Quartile B; 151+/-4.3 mmol/liter for Quartile C; and 162+/-6.6
      mmol/liter for Quartile D, respectively (mean+/- standard deviation). Mean
      occurrence of primary graft failure (PGF) was 3.6% with the following quartile
      breakdown: A, 3.6%; B, 4.8%; C, 3.6%; and D, 2.4% (p=non-significant [NS]). Mean
      5-year survival was 81.32% with: A, 83.51%; B, 76.03%; C, 80.47%; and D, 85.25%
      (p=NS). Coronary allograft vasculopathy (CAV) occurred in 19% of patients with a
      quartile breakdown of: A, 16.5%; B, 21%; C, 20%; and D, 14.5% (p=NS). No impact
      of donor serum sodium levels was seen on early post-operative results or on long
      term outcome, indicating that cardiac allografts from donors with elevated sodium
      levels may be transplanted successfully with favorable results.

PMID- 15982626
TI  - Accident analysis and prevention 37 (2005).

PMID- 15982625
TI  - Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant
      recipient.
AB  - Chronic rejection is the major hurdle to long-term survival after lung
      transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in
      patients with chronic rejection and this may further contribute to deterioration
      of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa
      airways infection in patients with cystic fibrosis. The safety of inhaled
      tobramycin in transplant recipients, however, has not been established. We
      describe the first report of a lung transplant recipient who developed renal
      failure and vestibular injury after receiving inhaled tobramycin. We review the
      literature regarding the safety of inhaled tobramycin and discuss potential
      mechanisms that may promote systemic toxicity in transplant recipients.

PMID- 15982627
TI  - Individual differences in causal learning and decision making.
AB  - In judgment and decision making tasks, people tend to neglect the overall
      frequency of base-rates when they estimate the probability of an event; this is
      known as the base-rate fallacy. In causal learning, despite people's accuracy at
      judging causal strength according to one or other normative model (i.e., Power
      PC, DeltaP), they tend to misperceive base-rate information (e.g., the cause
      density effect). The present study investigates the relationship between causal
      learning and decision making by asking whether people weight base-rate
      information in the same way when estimating causal strength and when making
      judgments or inferences about the likelihood of an event. The results suggest
      that people differ according to the weight they place on base-rate information,
      but the way individuals do this is consistent across causal and decision making
      tasks. We interpret the results as reflecting a tendency to differentially weight
      base-rate information which generalizes to a variety of tasks. Additionally, this
      study provides evidence that causal learning and decision making share some
      component processes.

PMID- 15982628
TI  - The quantification of chondroitin sulfates by rocket electrophoresis.

PMID- 15982629
TI  - [Morbi-mortality after Hartmann procedure for peritonitis complicating sigmoid
      diverticulitis. A retrospective analysis of 85 cases].
AB  - INTRODUCTION: Hartmann's procedure (HP) is a simple operation, which can be
      performed by all the surgeons. However, it remains criticized (high
      morbimortality, low rate of intestinal continuity restoration). The aim of this
      study was to analyse natural history of HP and intestinal continuity restoration
      for sigmoid diverticulitis, and to assess risk factors for mortality, morbidity
      and absence of intestinal continuity restoration. PATIENTS AND METHODS: In three
      centers, from 1992 to 2002, 85 patients underwent HP. A retrospective analysis
      was performed on mortality, early and late morbidity of HP and intestinal
      continuity restoration. RESULTS: 22% of patients (mean age, 68 years) presented
      comorbidity, 17% of them, an altered immunity, and 3 or 4 Hinchey score for 64%.
      ASA score was > or =3 in 49% of the cases. Mean AFC and Mannheim scores were 2
      and 21 respectively. Mortality rate was 14% and in-hospital morbidity, 50%. Main
      complications were: cardiorespiratory (18%), wound abcess (14%) and stomal (6%).
      No rectal stump fistula was noted. Mean hospital stay was 19+/-13 days. Late
      morbidity rate was 29%, mainly due to stomal complications (12%) and small bowel
      obstruction (7%). Intestinal continuity restoration was done in 77% of the cases,
      followed by only 1 fistula. Mortality rate for intestinal continuity restoration
      was 0% and morbidity was 13%. Mean hospital stay was 10+/-3 days. Age >75 years,
      ASA score > or =3 and comorbidity were risk factors for morbidity and mortality
      and for absence of intestinal continuity restoration. CONCLUSIONS: HP is
      associated with a high morbidity and mortality rates. Intestinal continuity
      restoration rate was high in this series. HP is a simple operation in high-risk
      patients with advanced peritonitis. This study allows to precise natural history
      of HP. Knowledge of this history is crucial for choosing the best operation
      (between HP and anastomosis) for patient with peritonitis complications sigmoid
      diverticuitis.

PMID- 15982630
TI  - [Inferior mesenteric arteriovenous fistulas. Report of a case].
AB  - We report a case of postoperative inferior mesenteric arteriovenous fistula.
      Arteriovenous fistula represents a rare disease. Symptoms are due to portal
      hypertension and distal ischemy. Treatment of these fistulas is embolization.
      Surgery is possible by ligature or excision of the fistula because
      vascularisation is obtained by Riolan arcade and hypogastric artery.

PMID- 15982631
TI  - [Fistula between Wirsung and psoas muscle].
AB  - We describe a rare case of fistula between the Wirsung duct and the right psoas
      muscle. The initial clinical presentation was localised in the thigh and
      successful treatment was achieved by exclusive mini-invasive techniques.

PMID- 15982632
TI  - Are simple feedback interventions involving workplace data associated with better
      working environment and health? A cluster randomized controlled study among
      Swedish VDU workers.
AB  - OBJECTIVE: To test whether feedback and discussion of ergonomic and psychosocial
      working environment data during 1 short session with individual, groups, or
      supervisors of VDU workers had effects on (1) the quality of implemented
      modifications in workplace design, working technique, or psychosocial aspects;
      (2) psychological demands, decision latitude, and social support; (3) comfort
      during computer work, emotional stress, and prevalence of musculoskeletal
      symptoms or eye discomfort. METHODS: Thirty-six workgroups from 9 organizations
      were randomized to 3 feedback conditions (individual, workgroup, supervisor) or
      control. Follow-up was 6 months after intervention. Questionnaire data aggregated
      on the workgroup level were used. RESULTS: Effect (positive) on social support
      was indicated from feedback to supervisors. CONCLUSION: Feedback and discussion
      of ergonomic and psychosocial working environment data with supervisors of white
      collar VDU workers may have positive effect on social support measured as a group
      characteristic. Sources of potential bias are discussed.

PMID- 15982633
TI  - API2-MALT1 fusion protein induces transcriptional activation of the API2 gene
      through NF-kappaB binding elements: evidence for a positive feed-back loop
      pathway resulting in unremitting NF-kappaB activation.
AB  - t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal
      translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this
      translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has
      been shown to enforce activation of NF-kappaB signaling, the transcriptional
      target genes of this fusion protein remains to be identified. Our analyses of the
      API2-MALT transfectants suggested that one of the target genes may be the
      apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and
      mutational constructs of the API2 promoter and electrophoretic mobility shift
      assays established that API2-MALT1 induces transcriptional activation of the API2
      gene through two NF-kappaB binding elements. Moreover, supershift experiments
      indicated that these elements are recognized by the NF-kappaB p50/p65
      heterodimer. Taken together, our results strongly indicated that API2-MALT1
      possesses a novel mechanism of self-activation by up-regulating its own
      expression in t(11;18)(q21;q21)-carrying MALT lymphomas, highlighting a positive
      feedback-loop pathway resulting in unremitting NF-kappaB activation.

PMID- 15982634
TI  - EGF receptor-ligand interaction generates extracellular hydrogen peroxide that
      inhibits EGFR-associated protein tyrosine phosphatases.
AB  - Hydrogen peroxide (H(2)O(2)) has been shown to be an important modulator of
      intracellular phosphatase activity involved in cell signaling pathways, including
      signaling by members of the receptor tyrosine kinase family of receptors such as
      the epidermal growth factor receptor (EGFR). Intracellular H(2)O(2) can be
      generated by mitochondria-dependent pathways, whereas we recently showed that
      H(2)O(2) could be generated extracellularly by receptor-ligand interaction. Here,
      we show that H(2)O(2) produced by EGF-EGFR interaction can modulate the activity
      of intracellular protein tyrosine phosphatases (PTPs). Using purified proteins,
      we found that EGFR-ligand interaction generates H(2)O(2) that is capable of
      inhibiting the activity of PTP1B in vitro. Furthermore, the addition of catalase
      rescued phosphatase inhibition consequent to EGF-EGFR interaction. Using cells
      that overexpress EGFR, we found that the addition of extracellular catalase
      prevented EGF-induced inhibition of EGFR-associated phosphatase activity. Our
      findings suggest that extracellular H(2)O(2) generated by EGFR-ligand interaction
      permeates the plasma membrane and inhibits EGFR-associated tyrosine phosphatase
      activity, thereby modulating downstream signal transduction pathways.

PMID- 15982635
TI  - c-Krox down-regulates the expression of UDP-glucose dehydrogenase in
      chondrocytes.
AB  - Chondrocyte glycosaminoglycan (GAG) synthesis is regulated by the availability of
      UDP-glucuronate, the substrate of glucuronosyl transferases which form the GAG
      chains in proteoglycans and hyaluronan. UDP-glucose dehydrogenase (UDPGD) is
      therefore a key enzyme in the synthesis of UDP-glucuronate from glucose. However,
      the mechanisms regulating its expression in chondrocytes are not fully
      understood. We investigated the effect of c-Krox, a zinc-finger transcription
      factor previously shown to modulate several matrix genes, on the synthesis of GAG
      and transcriptional activity of several UDPGD gene promoter constructs, using
      transient transfection and decoy experiments in rabbit articular chondrocytes
      (RACs). We show that overexpression of c-Krox inhibits radiosulfate incorporation
      into neosynthesized GAG and that the effect was mediated by a cis-sequence
      located between +18 and +39bp of the UDPGD gene. Since that sequence can also
      bind Sp1/Sp3 factors, it is likely that c-Krox acts in concert with these
      proteins to modulate the UDPGD gene expression in articular chondrocytes.

PMID- 15982636
TI  - Interaction of Bcr/Abl with C3G, an exchange factor for the small GTPase Rap1,
      through the adapter protein Crkl.
AB  - The Bcr/Abl oncoprotein is directly responsible for the development of chronic
      myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic
      leukemia in humans. The adapter protein Crkl is one of the most prominently
      tyrosine-phosphorylated substrates of Bcr/Abl in cells and tissues isolated from
      such patients. The guanine nucleotide exchange factor for the small GTPase Rap1,
      C3G, binds constitutively to Crkl. Here, we report that Crkl mediates the
      formation of protein complexes that include C3G and Bcr/Abl. These complexes
      contain highly elevated levels of tyrosine-phosphorylated C3G and P130Cas, a
      scaffolding protein. Moreover, the presence of Rap1 further promoted tyrosine
      phosphorylation of C3G and Cas. Co-expression of Crkl and C3G with Bcr/Abl
      generated increased levels of activated Rap1. In addition, lysates from leukemic
      cells of P190 BCR/ABL transgenic mice and of the myelogenous leukemia cell line
      K562 contained tyrosine-phosphorylated C3G and activated Rap1. These data suggest
      a role for C3G-mediated Rap1 activation in Bcr/Abl-induced leukemia development.

PMID- 15982637
TI  - Allelic dosage analysis with genotyping microarrays.
AB  - Genomic alternations, including dosage and allelic imbalance, constitute a major
      basis of neoplastic and other genetic disorders. Using oligonucleotide genotyping
      microarrays, here we report the development and usage of an algorithm, called
      genome imbalance map (GIM) algorithm, for allelic as well as total gene dosage
      analysis. Using the GIM algorithm, global genome imbalance status at over 100,000
      loci was simultaneously analyzed with unprecedented accuracy and allelic
      discrimination.

PMID- 15982638
TI  - RXR agonist enhances the differentiation of cardiomyocytes derived from embryonic
      stem cells in serum-free conditions.
AB  - Signaling from the retinoic acid receptors (RARs) and retinoid X receptors (RXRs)
      is essential for cardiovascular morphogenesis in vivo. RAR and/or RXR signaling
      can also enhance the in vitro induction of cardiomyocytes from murine embryonic
      stem (ES) cells in the presence of serum. The present study examined the effect
      of RXR agonist that was specifically bound to RXRs on the differentiation of
      mouse ES cells into cardiomyocytes in vitro in the absence of serum. The number
      of beating embryoid body-like spheres (EBSs) derived from the ES cells increased
      significantly following treatment with PA024, an RXR agonist. In contrast, when
      EBSs were treated with PA452, which was specifically bound to RXR and worked as
      an antagonist, the number of beating EBSs was decreased in a dose-dependent
      manner. These results suggest that RXR signaling regulates cardiomyocyte numbers
      during the differentiation of ES cells in vitro and probably in normal
      development.

PMID- 15982639
TI  - Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1.
AB  - Mixl1 is a paired-type homeodomain protein that plays a crucial role in
      morphogenesis and endoderm differentiation in the murine embryo. To understand
      how Mixl1 directs embryogenesis, we studied the regulation of Mixl1 expression at
      a transcriptional level. In HepG2 cells, a genomic fragment encompassing the
      Mixl1 promoter conferred strong TGF-beta-induced transcription that was dependent
      on the presence of the DNA-binding protein FoxH1. Further analysis of the Mixl1
      promoter identified a proximal response element (PRE) containing SMAD- and FoxH1
      binding sites required for TGF-beta responsiveness. The PRE was also responsive
      to signalling by Nodal, a TGF-beta ligand required for normal embryonic
      patterning. These results demonstrate for the first time a functional role for
      TGF-beta ligands in regulation of mammalian Mixl1, identify FoxH1 as an essential
      transcriptional co-activator, and implicate Nodal as the embryonic regulator of
      Mixl1 in mesendoderm morphogenesis.

PMID- 15982640
TI  - Mechanism of action of a novel "combi-triazene" engineered to possess a polar
      functional group on the alkylating moiety: evidence for enhancement of potency.
AB  - Previous studies showed that SMA41, a 3-methyltriazene termed "combi-molecules"
      possessing a dual epidermal growth factor receptor (EGFR)/DNA targeting
      properties induced potent antiproliferative activity against alkylating-agent
      resistant cells expressing EGFR in vitro. However, despite its marked potency,
      its antitumour activity in vivo was significantly hampered by its poor
      hydrosolubility and the moderate reactivity of its alkylating moiety. To
      circumvent this problem, we designed the quinazolinotriazene ZRBA1 to contain a
      N,N-dimethylaminoethyl group grafted to the 3-position of the triazene chain
      where it could serve both as a water soluble and a more potent alkylating moiety.
      ZRBA1 exhibited five-fold stronger EGFR tyrosine kinase (TK) inhibitory activity
      (IC(50)=37nM) than SMA41, decomposed into a 6-amino-quinazoline FD105
      (IC(50)=200nM) and preferentially blocked EGF- over platelet-derived growth
      factor (PDGF)-or serum-induced cell growth. ZRBA1 induced DNA damage,
      concomitantly blocked EGF-stimulated EGFR phosphorylation by a partially
      irreversible mechanism in MDA-MB-468 breast cancer cells, and induced partially
      irreversible antiproliferative activity. It also prevented EGFR-mediated MAP
      kinase activation and, in contrast to FD105 and SMA41, induced high levels of
      apoptosis. Furthermore, ZRBA1 showed significantly greater antitumor activity
      (p<0.05) than SMA41 in the human MDA-MB-468 breast cancer xenograft model. The
      results in toto indicate that the appendage of N,N-dimethylaminoethyl to combi
      triazenes may be an alternative to the reduced hydrosolubility and also to the
      lack of potency of monofunctional combi-triazenes against resistant tumours.

PMID- 15982641
TI  - The effect of AZT and chloroquine on the activities of ricin and a saporin
      transferrin chimeric toxin.
AB  - This study deals with the combination of chloroquine (CQ, an anti-malaric drug)
      and 3'-azido-3'-deoxythymidine (AZT, anti-human immuno-deficiency virus (HIV)
      drug) with a chimeric toxin (TS) obtained by chemical linking of saporin (a
      ribosome inactivating protein from the plant Saponaria officinalis) and human
      transferrin, in the intoxication of the human chronic myeloid leukaemia cells
      (K562). Our data demonstrate that AZT, at concentrations comparable to those
      reached in the blood of HIV-infected patients under pharmacological treatment
      with this drug, can increase the toxicity of TS in cooperation with CQ inducing
      an increased effect on protein synthesis in K562 cells ( approximately 50%
      inhibition of protein synthesis for TS alone, and TS with AZT and approximately
      70% with both AZT and CQ). Furthermore, pre-treatment of cells with AZT alone can
      induce an increase of apoptosis in K562 cells intoxicated with TS. By comparing
      data obtained with the model toxin ricin, we get indications that the two toxins
      partially differ in their intracellular routes, also suggesting that chimeric
      constructs containing ricin-like toxins (i.e. immunotoxins) could be coupled with
      the use of common and cheap drugs for the treatment of cancer in HIV-infected
      patients.

PMID- 15982642
TI  - Instantaneous acceleration and amplification of hippocampal theta wave coincident
      with phasic pontine activities during REM sleep.
AB  - Rapid eye movement (REM) sleep is characterized by hippocampal theta waves and
      phasic spike-like waves originating from the pons, termed ponto-geniculo
      occipital (PGO) waves in cats and pontine (P) waves in rats. While the theta wave
      and PGO/P wave have been suggested to participate in higher-order brain
      functions, their generation mechanisms and roles in brain functions have been
      studied independently. Therefore, the present study investigated instantaneous
      aspects of the relationship between theta waves and PGO/P waves in both cats and
      rats. Theta wave was instantaneously accelerated several hundred milliseconds
      before the negative peak of the PGO/P wave in both animals, and was also
      amplified just before PGO/P wave occurrence. Considering the integrated knowledge
      provided by studies of both animals, these results suggest that PGO/P wave
      related activities in the pons are delivered to the theta wave generator. The
      activations of the theta wave coincident with PGO/P wave might facilitate
      cooperative contribution to higher-order brain functions in REM sleep.

PMID- 15982643
TI  - Cholinergic involvement in the cortical and hippocampal Fos expression induced in
      the rat by placement in a novel environment.
AB  - Placing rats into a series of novel environments induced vigorous c-fos
      expression in the infralimbic, anterior cingulate and retrosplenial cortices, and
      in the hippocampus. Pretreatment with the antimuscarinic drugs scopolamine and
      atropine was able to greatly suppress novelty-induced Fos expression at these
      sites. Placement into the novel environments also induced Fos expression in the
      habenula and the paraventricular thalamic nucleus, but the response at these
      sites did not appear to be sensitive to cholinergic blockade. These findings
      suggest that cholinergic mechanisms play an important role in ability of
      behavioral events to influence cortical and hippocampal immediate-early gene
      expression and are consistent with the possibility that some of the effects of
      anticholinergic drugs on placticity and learning may be mediated through
      alterations in the expression of these genes.

PMID- 15982644
TI  - Synaptic localization of receptor-type protein tyrosine phosphatase zeta/beta in
      the cerebral and hippocampal neurons of adult rats.
AB  - Receptor-type protein tyrosine phosphatase (RPTP) zeta/beta is a nervous tissue
      specific chondroitin sulfate proteoglycan. In this study, we investigated the
      immunohistochemical localization of RPTPzeta/beta in adult rat cerebral cortex
      and hippocampus at light and electron microscopic levels. Double labeling
      immunofluorescence microscopy revealed that the immunoreactivity of RPTPzeta/beta
      was observed at MAP2-positive dendrites and PSD-95-positive spines of pyramidal
      neurons in the cerebral cortex and hippocampus. Electron microscopic observation
      demonstrated a strong immunoreactivity of RPTPzeta/beta at the postsynaptic
      membrane of dendritic spines and shafts, and its moderate immunoreactivity at the
      dendritic membrane. In cultured cortical neurons, the immunoreactivity of
      RPTPzeta/beta was observed at some of PSD-95-positive spines. These results
      demonstrate that RPTPzeta/beta is localized mainly at the postsynaptic membrane
      of pyramidal neurons in adult cerebral cortex and hippocampus.

PMID- 15982645
TI  - The effect of experimental muscle pain on the amplitude and velocity sensitivity
      of jaw closing muscle spindle afferents.
AB  - The effect of experimental muscle pain on the amplitude and velocity sensitivity
      of muscle spindle primary afferent neurons in the trigeminal mesencephalic
      nucleus (Vmes) was examined. Extracellular recordings were made from 45 neurons
      designated as spindle primary- or secondary-like on the basis of their response
      to ramp-and-hold jaw movements. Velocity sensitivity was assessed in spindle
      primary-like afferents by calculating the mean dynamic index of each unit in
      response to three different velocities of jaw opening before and after
      intramuscular injection with hypertonic saline (HS, 5%, 100 microl). The
      amplitude sensitivity of all jaw muscle spindle afferents was assessed by
      calculating the mean firing rate of each unit in response to three different
      amplitudes of jaw openings during both the open and hold phases of the movement
      and with best-fit lines obtained, using linear regression analysis, before and
      after HS injection. The variance of the two regression lines obtained for each
      unit before and after the injection was compared using the coincidence test, and
      changes in intercept and slope were determined. Seventy-five percent of the
      primary-like units and 80% of the secondary-like units presented with changes in
      static behavior after HS injection. Thirty-six percent of the primary-like units
      showed changes in dynamic behavior. Injection of isotonic saline (control) did
      not alter the responses of the spindle afferent to jaw opening. Thus, our results
      demonstrate that the predominant effect of noxious stimulation was a shift in the
      amplitude sensitivity of both spindle primary-like and secondary-like afferents
      and, to a lesser extent, the velocity sensitivity of the spindle primary-like
      unit. In accordance with earlier studies in the cat hindlimb and neck muscles,
      these results suggest that the activation of masseter muscle nociceptor alters
      spindle afferent responses to stretch acting primarily through static gamma motor
      neurons.

PMID- 15982646
TI  - Mechanisms of endothelial dysfunction in obesity.
AB  - Obesity is a chronic disease, whose incidence is alarmingly growing, affecting
      not only adults but also children and adolescents. It is associated with severe
      metabolic abnormalities and increased cardiovascular morbidity and mortality.
      Adipose tissue secretes a great number of hormones and cytokines that not only
      regulate substrate metabolism but may deeply and negatively influence endothelial
      physiology, a condition which may lead to the formation of the atherosclerotic
      plaque. In this review, the physiology of the endothelium is summarised and the
      mechanisms by which obesity, through the secretory products of adipose tissue,
      influences endothelial function are explained. A short description of
      methodological approaches to diagnose endothelial dysfunction is presented. The
      possible pathogenetic links between obesity and cardiovascular disease, mediated
      by oxidative stress, inflammation and endothelial dysfunction are described as
      well.

PMID- 15982647
TI  - Asymmetric PCR increases efficiency of melting peak analysis on the LightCycler.
AB  - OBJECTIVES: To systematically analyze the effects of asymmetric PCR on
      LightCycler melting analyses of four different allelic-discrimination systems and
      to reduce an inconsistent non-specific melting peak observed during factor V
      Leiden genotyping. DESIGN AND METHODS: PCR amplifications and melting analyses
      were carried out with various oligonucleotide concentrations and ratios. To
      monitor the efficiency, calculated peak area values were compared after melting
      analyses. RESULTS: Peak area values increased by a mean of 11.2-fold (range: 6 to
      17) in case of an amplification primer ratio of 1:6.7 asymmetric PCR compared to
      symmetric primer conditions in four different SNP-genotyping systems. Using a
      complementary hybridization probe set for factor V Leiden genotyping, a converse
      amplification primer ratio was necessary for similar results. CONCLUSIONS:
      Asymmetric PCR resulting in the formation of higher amounts of target strands
      significantly increases the efficiency of LightCycler allelic-discrimination.

PMID- 15982648
TI  - Computational analysis of EGFR inhibition by Argos.
AB  - Argos, a secreted inhibitor of the Drosophila epidermal growth factor receptor,
      and the only known secreted receptor tyrosine kinase inhibitor, acts by
      sequestering the EGFR ligand Spitz. We use computational modeling to show that
      this biochemically-determined mechanism of Argos action can explain available
      genetic data for EGFR/Spitz/Argos interactions in vivo. We find that efficient
      Spitz sequestration by Argos is key for explaining the existing data and for
      providing a robust feedback loop that modulates the Spitz gradient in embryonic
      ventral ectoderm patterning. Computational analysis of the EGFR/Spitz/Argos
      module in the ventral ectoderm shows that Argos need not be long-ranged to
      account for genetic data, and can actually have very short range. In our models,
      Argos with long or short length scale functions to limit the range and action of
      secreted Spitz. Thus, the spatial range of Argos does not have to be tightly
      regulated or may act at different ranges in distinct developmental contexts.

PMID- 15982650
TI  - Associations between ambient air pollution and daily mortality among persons with
      diabetes and cardiovascular disease.
AB  - BACKGROUND: Recent studies suggest that persons with diabetes and with
      cardiovascular disease may be at higher risk for the short-term effects of air
      pollution. We carried out this mortality time series study in Montreal, Quebec,
      Canada to confirm these observations and to determine whether diabetics who had
      other health conditions were also at higher risk of dying when air pollution
      increases. METHODS AND RESULTS: In one analysis, we related daily deaths from
      diabetes (using the underlying cause) to daily concentrations of particles and
      gaseous pollutants. In another analysis, we created subgroups by identifying
      subjects diagnosed 1 year before death with diabetes and other major health
      conditions from billing and prescription data from the universal Quebec Health
      Insurance Plan. The analysis made use of parametric log-linear Poisson models
      that were adjusted for long-term temporal trends and daily weather conditions. We
      found positive associations between most air pollutants and daily mortality from
      diabetes as well as among subjects diagnosed with diabetes 1 year before death.
      In the latter group of subjects, greater effects were found generally in the warm
      season and especially among subjects who had diabetes and who also had any
      cardiovascular disease, chronic coronary disease, and atherosclerosis. We did not
      find evidence of associations among persons who only had diabetes (i.e., did not
      also have cancer, cardiovascular disease, or lower respiratory disease).
      CONCLUSIONS: These data indicate that individuals with diabetes who also have
      cardiovascular disease may be susceptible to the short-term effects of air
      pollution.

PMID- 15982649
TI  - Mouse SLLP1, a sperm lysozyme-like protein involved in sperm-egg binding and
      fertilization.
AB  - This study demonstrates the retention of mouse sperm lysozyme-like protein
      (mSLLP1) in the equatorial segment of spermatozoa following the acrosome reaction
      and a role for mSLLP1 in sperm-egg binding and fertilization. Treatment of
      cumulus intact oocytes with either recmSLLP1 or its antiserum resulted in a
      significant (P < or = 0.05) inhibition of fertilization. Co-incubation of zona
      free mouse oocytes with capacitated mouse spermatozoa in the presence of varying
      concentrations of anti-recmSLLP1 serum or recmSLLP1 also inhibited sperm-oolemma
      binding. A complete inhibition of binding and fusion of spermatozoa to the oocyte
      occurred at 12.5 muM concentration of recmSLLP1, while conventional chicken and
      human lysozymes did not block sperm-egg binding. mSLLP1 showed receptor sites in
      the perivitelline space as well as on the microvillar region of the egg plasma
      membrane. The retention of mSLLP1 in the equatorial segment of acrosome-reacted
      sperm, the inhibitory effects of both recmSLLP1 and antibodies to SLLP1 on in
      vitro fertilization with both cumulus intact and zona-free eggs, and the
      definition of complementary SLLP1-binding sites on the egg plasma membrane
      together support the hypothesis that a c lysozyme-like protein is involved in the
      binding of spermatozoa to the egg plasma membrane during fertilization.

PMID- 15982651
TI  - The effects of early rearing environment on the hormonal induction of maternal
      behavior in virgin rats.
AB  - The present study investigated the effects of isolation rearing, through the
      artificial rearing paradigm (AR), on the hormonal induction of maternal behavior
      (MB) in female Sprague-Dawley rats. Between postnatal days (PND) 4 and 18, rat
      pups were raised either with their mothers (MR) or artificially, without their
      mothers (AR). As well, some of the AR pups were provided with additional maternal
      like licking stimulation (AR-MAX) while the others were not given any additional
      stimulation (AR-MIN). At PND 60-100, AR (n = 28) and MR (n = 25) animals were
      ovariectomized (OVX). One week after the surgery, rats were either treated with a
      2-week estrogen (E2) and progesterone (P) hormonal regimen or not treated with
      the hormone replacement. Maternal behavior testing with foster pups commenced 24
      h following the removal of P treatment. Results demonstrated that MR animals
      showed increased pup licking and hover-crouching in comparison to AR animals and
      that hormonally primed groups became maternal more quickly than non-primed
      groups, regardless of the rearing history. There was also a significant
      interaction between the rearing condition (MR vs. AR) and hormonal treatment on
      the quality of maternal behavior exhibited. The highest level of licking and
      crouching was shown by the hormone-treated MR group. Mechanisms for these effects
      are discussed.

PMID- 15982652
TI  - Response of circulating immune cells to major gunshot injury, haemorrhage, and
      acute surgery.
AB  - PURPOSE: The purpose of this study was to use an established porcine model to
      investigate the effects on immune function of severe gunshot injury. METHODS:
      Twelve pigs sustained two standardised rounds, one through right femur and one
      through left upper abdomen. First aid treatment and acute surgery was started
      immediately. Blood samples were drawn before shooting and after 75 min.
      Circulating neutrophils were isolated and reactive oxygen species (ROS) measured.
      Serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL
      1beta), IL-6, and IL-10 were determined at 0, 75 min, as well as 2h after
      incubation with 1 microg/ml endotoxin in an ex vivo whole blood model. RESULTS:
      TNF-alpha, IL-1beta, and IL-6 significantly increased at 75 min. ROS in
      circulating granulocytes tended to increase (NS). Incubation with endotoxin led
      to a more than 100-fold increase of TNF-alpha pre-trauma, compared to a three
      fold increase post-trauma (p<0.0001 between groups). A similar pattern was
      obtained for IL-1beta, and IL-6. IL-10 was below detection in all samples. The
      granulocytes maintained their ability to react to the protein kinase C activator
      phorbol myristate acetate (PMA) after trauma. CONCLUSION: Severe gunshot injury
      and peritraumatic stress rapidly activate circulating immune cells, but reduce
      their capacity to react to a subsequent challenge to endotoxin.

PMID- 15982653
TI  - Coronal fractures of the distal femoral condyle: a biomechanical evaluation of
      four internal fixation constructs.
AB  - This study evaluated different fixation methods in posterior femoral condyle
      coronal fractures. A standardised osteotomy was created in synthetic composite
      femurs and fixed with one of four methods (one 3.5 mm diameter screw, two 3.5 mm
      screws, one 6.5 mm screw, two 6.5 mm screws). The stiffness and mean loads to
      specified displacements were measured. The stiffness of two 6.5 mm screws was
      significantly greater than both single 3.5 mm screw (3567 versus 2584N/mm;
      p=0.0075) and double 3.5 mm screws (3567 versus 2080N/mm; p=0.003). There was no
      statistical difference in the stiffness of one 6.5 mm screw compared to either
      the single or double 3.5mm screws. Increasing the screw diameter and using two
      screws increased the load at 1, 2 and 3 mm of displacement. In the fixation of
      posterior femoral condyle fractures, two 6.5 mm screws are more rigid than either
      single or double 3.5 mm screws. The use of a second screw marginally increases
      the rigidity of fixation. If 3.5 mm screws are used in the fixation of posterior
      femoral condyle fractures, at least two screws should be used to approximate the
      biomechanical stability of a single 6.5 mm screw.

PMID- 15982654
TI  - Outcome of tibial plateau fractures managed with calcium phosphate cement Re:
      letter to the editor about an article in Injury 35 (2004) 913-918.

PMID- 15982655
TI  - Diagnostic accuracy of surgeon-performed focused abdominal sonography (FAST) in
      blunt paediatric trauma.
AB  - AIM: To study the diagnostic accuracy and clinical efficacy of surgeon-performed
      focused abdominal sonography (FAST) in paediatric blunt abdominal trauma (BAT).
      MATERIALS AND METHOD: This was a prospective, single blinded study conducted at
      The Children's Hospital at Westmead Sydney (CHW). All patients with BAT that
      justified a trauma call activated on presentation to the Emergency Department
      (ED) had a FAST performed by the Trauma Fellow. The attending surgical team was
      blinded to the result of the FAST. An independent radiologist reviewed the FAST
      pictures, and the findings were compared with computerised tomography (CT),
      ultrasound (US), laparotomy and the clinical outcome of the patient. Sensitivity,
      specificity and predictive values were calculated. RESULTS: A total of 85
      patients (39 M; 26 F) were enrolled in the study between February 2002 and
      January 2003. The age ranged between 4 months and 16 years. The mean Injury
      Severity Score (ISS) was 6 (range 1-38). FAST was performed in a mean time of 3
      min. Inter-rater agreement was 96%. FAST was positive in nine as confirmed by a
      CT scan of the abdomen. Three patients underwent laparotomy, two for bowel
      injuries and one for a Grade III liver laceration. Of the remaining 76, 19 had a
      CT, which showed evidence of intra-abdominal injury in seven patients. There were
      two false negative studies resulting in a sensitivity of 81%, specificity of
      100%, negative predictive value of 97%, positive predictive value of 100% and an
      accuracy of 97%. CONCLUSIONS: Surgeon-performed FAST for BAT was safe and
      accurate with a high specificity. It would seem a potentially valuable tool in
      the evaluation of paediatric blunt trauma victims for free fluid within the
      peritoneal cavity.

PMID- 15982656
TI  - Examination of a novel head-stalk protein family in Giardia lamblia characterised
      by the pairing of ankyrin repeats and coiled-coil domains.
AB  - The intestinal pathogen Giardia lamblia possesses several unusual organelle
      features, including two equivalent nuclei, no mitochondria or peroxisomes, and a
      developmentally regulated rough endoplasmic reticulum and Golgi. Giardia also
      possesses a number of complex and unique cytoskeleton structures that dictate
      cell shape, motility and attachment. Our investigations of cytoskeletal proteins
      have revealed the presence of a new protein family. Proteins in this family
      contain both ankyrin repeats and coiled-coil domains; although these are common
      protein motifs, their pairing is unique, thus establishing a new class of head
      stalk proteins. Examination of the G. lamblia genome shows evidence for at least
      18 genes coding for proteins with a series of ankyrin repeats followed by a
      lengthy coiled-coil domain and at least an additional 14 genes coding for
      proteins with a prominent coiled-coil domain flanked by two series of ankyrin
      repeats. We have examined one of these proteins, Giardia Axoneme Associated
      Protein (GASP-180), in detail. GASP-180 is a 180 kDa protein containing five
      ankyrin repeats in a 200 amino acid N-terminal domain separated by a short spacer
      from an approximately 1375 amino acid coiled-coil domain. Using anti-peptide
      antibodies raised against a unique 20 amino acid sequence found at the C
      terminus, we have determined that GASP-180 is present in cytoskeleton extractions
      of the parasite and localises to the proximal base of the anterior flagellar
      axonemes. The combination of the localisation and the structural and functional
      motifs of GASP-180 make it a strong candidate to participate in control of
      flagellar activity.

PMID- 15982657
TI  - Rho and vascular disease.
AB  - The Rho family GTPases are regulatory molecules that link surface receptors to
      organisation of the actin cytoskeleton and play major roles in fundamental
      cellular processes. In the vasculature Rho signalling pathways are intimately
      involved in the regulation of endothelial barrier function, inflammation and
      transendothelial leukocyte migration, platelet activation, thrombosis and
      oxidative stress, as well as smooth muscle contraction, migration, proliferation
      and differentiation, and are thus implicated in many of the changes associated
      with atherogenesis. Indeed, it is believed that many of the beneficial, non-lipid
      lowering effects of statins occur as a result of their ability to inhibit Rho
      protein activation. Conversely, the Rho proteins can have beneficial effects on
      the vasculature, including the promotion of endothelial repair and the
      maintenance of SMC differentiation. Further identification of the mechanisms by
      which these proteins and their effectors act in the vasculature should lead to
      therapies that specifically target only the adverse effects of Rho signalling.

PMID- 15982658
TI  - The effect of statin therapy on lipoprotein associated phospholipase A2 levels.
AB  - Lipoprotein associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and
      inflammation, has been associated with increased coronary heart disease (CHD)
      risk. To date, data examining the effect of HMG CoA reductase inhibitors on Lp
      PLA2 are few. We evaluated the effect of pravastatin 40 mg daily versus placebo
      on Lp-PLA2 levels among 481 subjects free of cardiovascular disease (pravastatin
      N=246 and placebo N=235) who participated in the Pravastatin Inflammation/CRP
      Study (PRINCE). After 12 weeks, Lp-PLA2 levels decreased by 22.1% among
      pravastatin treated participants and by 7.8% among those randomized to placebo
      (p<0.001). These results were similar in all subgroups evaluated according to
      age, blood pressure, lipid parameters, diabetic status, smoking status, aspirin
      use, body mass index and gender. There were correlations between change in Lp
      PLA2 levels and baseline Lp-PLA2 levels (r=-0.63, p<0.001), total cholesterol
      change (r=-0.26, p<0.001), LDL-C change (r=-0.32, p<0.001) and C-reactive protein
      (CRP) change (r=-0.13, p=0.05). Multivariate linear regression models that
      assessed the relationship between the log difference in Lp-PLA2 at 12 weeks and
      treatment revealed a beta-coefficient of 0.15 for the treatment variable
      (p<0.01). However, adjustment for change in LDL-C substantially attenuated the
      beta-coefficient associated with treatment to 0.07 (P<0.005) and after additional
      control for other potential confounders, the effect of treatment was no longer
      significant. Thus, Lp-PLA2 levels were significantly reduced at 12 weeks by
      pravastatin, an effect that was significantly related to LDL cholesterol
      reduction accounting for about 6% of the variability in this response. Moreover,
      pravastatin induced reduction in Lp-PLA2 was no longer significant after taking
      the latter into account.

PMID- 15982659
TI  - Ankle-arm blood pressure index as a correlate of preclinical carotid
      atherosclerosis in elderly Japanese men.
AB  - Peripheral artery disease correlates with preclinical carotid atherosclerosis in
      Western populations. However, little is known about this correlation in Asian
      populations. In a cross-sectional population-based study, we examined the
      correlation between peripheral arterial disease and carotid intima-media
      thickness (IMT) among 726 Japanese men aged 60-79 years. None of them had a
      history of clinical peripheral arterial disease. The ankle-to-arm systolic blood
      pressure index (AAI) was used as a surrogate estimate of peripheral arterial
      disease. Compared to men with AAI> or =0.90, those with AAI<0.90 were 1-4 years
      older, and had lower mean body mass index and higher prevalence of current
      smokers. The mean AAI correlated inversely and linearly with maximum IMT in the
      common and internal carotid arteries (CCA and ICA), and men with AAI<0.90 had
      higher prevalence of maximum ICA IMT > or =1.5mm than did those with AAI> or
      =0.90. The multivariate odds ratio (95% confidence interval) of maximum ICA IMT >
      or =1.5mm was 2.9 (1.0-8.4), while that of maximum CCA IMT> or =1.1mm was 1.4
      (0.5-3.8) for men with AAI<0.90 versus > or =1.30. The sensitivity was 65% and
      the specificity was 98% for low AAI to detect ICA IMT > or =1.5mm. Low AAI is a
      strong correlate for internal carotid atherosclerosis and the AAI measurement may
      be of use to screen for preclinical peripheral atherosclerosis among Japanese
      elderly men.

PMID- 15982660
TI  - Cathepsin L expression and regulation in human abdominal aortic aneurysm,
      atherosclerosis, and vascular cells.
AB  - The cysteine protease cathepsin L is one of the most potent mammalian elastases
      and collagenases, widely expressed at basal levels in most tested tissues and
      cell types, and regulated by pro-inflammatory stimuli. The inflammatory arterial
      diseases abdominal aortic aneurysm (AAA) and atherosclerosis involve extensive
      vascular remodeling that requires elastolysis and collagenolysis. This study
      examined the hypothesis that cathepsin L is over-expressed in human AAA and
      atherosclerotic lesions and its expression in vascular cell types found in these
      lesions is regulated by pro-inflammatory cytokines. Immunohistochemical and
      tissue extract immunoblot analysis demonstrated increased expression of cathepsin
      L in human AAA and atheromata and localized its expression to lesional smooth
      muscle cells (SMC), endothelial cells (EC), and macrophages. In primary cultured
      human SMC, EC, and monocyte-derived macrophages, pro-inflammatory cytokines or
      growth factors induced the expression of cathepsin L and its activity against
      extracellular collagen and elastin. Patients with coronary artery stenosis (n=65)
      had higher serum cathepsin L levels than those without lesions detectable by
      quantitative coronary angiography (n=30) (1.47+/-0.33 ng/ml versus 0.60+/-0.06
      ng/ml, p<0.02). A strong correlation between the percent of stenosis of left
      anterior descending coronary artery and serum cathepsin L levels in patients with
      stenosis (R=0.542, p<0.0001), also suggests involvement of cathepsin L in these
      vascular diseases.

PMID- 15982662
TI  - Determination of frictional conditions between electrode array and endosteum
      lining for use in cochlear implant models.
AB  - Frictional conditions between the electrode array (in cochlear implants) and the
      endosteum lining covering the walls of the interior scala tympani structure
      strongly influence the sliding behaviour of the electrode array. Friction
      coefficients, determined by a simple but effective method based on the impending
      slippage model of electrode arrays sliding over the endosteum lining are reported
      in this paper. In this study, friction coefficients of the Nucleus standard
      straight and the Contour arrays have been determined with and without lubricants
      applied on the endosteum lining. In the absence of applied lubricants, friction
      coefficients were found to be 0.19 for the Nucleus standard straight array and
      0.12 for the Contour array. Application of lubricants (glycerin and sorbelene)
      has the potential to lower the friction coefficient for Nucleus standard straight
      array (0.12 and 0.15) and for the Contour array (0.04 and 0.08). These results
      are used in finite element models to predict accurately the trajectories of
      electrode arrays and sliding contact pressures on cochlear structures to evaluate
      the likelihood of damage sustained during insertion.

PMID- 15982663
TI  - Quantitative immunohistochemistry of fluorescence labelled probes using low-cost
      software.
AB  - This paper describes simple procedures to process digital images in quantitative
      immunofluorescence microscopy. Monoclonal antibodies directed against the
      sarcoplasmic myosin heavy chain isoforms and against laminin, located on the
      basement membranes, were applied to sections of human skeletal muscle. The
      localisation and staining intensity of a fluorescent secondary antibody were
      recorded using an indirect histochemical method. The digitised images were pre
      processed and the luminosities of appropriate structures were determined using
      existing tools in the widely used image processing software Photoshop from Adobe.
      Procedures to obtain a quantitative measure for the specific fluorescence signal
      (the background corrected fluorescence in the object) were developed. In
      addition, antibody binding to individual cells could be quantified whether these
      cells are well separated or not. The relation between the specific fluorescence
      signal and the dilution factor of the primary antibody could be measured to
      determine a suitable concentration of the antibody for incubation of the
      sections. The potential fading of the fluorescence signal with time and prolonged
      exposure to light from the microscope was explored and analysed. With the tools
      described in the present report it is thus possible also to optimize the topical
      immunohistochemical protocol in order to quantify the fluorescence signal.

PMID- 15982664
TI  - The influence of collagenase treatment on the production of TNF-alpha, IL-6 and
      IL-10 by testicular macrophages.
AB  - Testicular macrophages (TMf) are located in the interstitial tissue of the male
      gonad. Highly purified TMf populations can be prepared either by the mechanical
      shaking of dispersed testicular tissues or by enzymatic digestion with
      collagenase followed by cell adherence, rosetting and gradient centrifugation.
      TMf obtained by the enzymatic procedure produced significantly more cytokines (IL
      6, IL-10 and TNF-alpha) than TMf isolated by the mechanical method and this
      effect is long-lasting. Our results indicate that isolation of tissue macrophages
      by enzymatic digestion may influence their functional activity, and suggest that
      critical evaluation of the method used to obtain these cells should be the
      regular practice.

PMID- 15982665
TI  - The 1.49 A resolution crystal structure of PsbQ from photosystem II of Spinacia
      oleracea reveals a PPII structure in the N-terminal region.
AB  - We report the high-resolution structure of the spinach PsbQ protein, one of the
      main extrinsic proteins of higher plant photosystem II (PSII). The crystal
      structure shows that there are two well-defined regions in PsbQ, the C-terminal
      region (residues 46-149) folded as a four helix up-down bundle and the N-terminal
      region (residues 1-45) that is loosely packed. This structure provides, for the
      first time, insights into the crucial N-terminal region. First, two parallel beta
      strands cross spatially, joining the beginning and the end of the N-terminal
      region of PsbQ. Secondly, the residues Pro9-Pro10-Pro11-Pro12 form a left-handed
      helix (or a polyproline type II (PPII) structure), which is stabilized by
      hydrogen bonds between the Pro peptide carbonyl groups and solvent water
      molecules. Thirdly, residues 14-33 are not visible in the electron density map,
      suggesting that this loop might be very flexible and presumably extended when
      PsbQ is free in solution. On the basis of the essential role of the N-terminal
      region of PsbQ in binding to PSII, we propose that both the PPII structure and
      the missing loop are key secondary structure elements in the recognition of
      specific protein-protein interactions between PsbQ and other oxygen-evolving
      complex extrinsic and/or intrinsic proteins of PSII. In addition, the PsbQ
      crystal coordinates two zinc ions, one of them is proposed to have a
      physiological role in higher plants, on the basis of the full conservation of the
      ligand protein residues in the sequence subfamily.

PMID- 15982666
TI  - Reconstruction of the src-SH3 protein domain transition state ensemble using
      multiscale molecular dynamics simulations.
AB  - We use an integrated computational approach to reconstruct accurately the
      transition state ensemble (TSE) for folding of the src-SH3 protein domain. We
      first identify putative TSE conformations from free energy surfaces generated by
      importance sampling molecular dynamics for a fully atomic, solvated model of the
      src-SH3 protein domain. These putative TSE conformations are then subjected to a
      folding analysis using a coarse-grained representation of the protein and rapid
      discrete molecular dynamics simulations. Those conformations that fold to the
      native conformation with a probability (P(fold)) of approximately 0.5, constitute
      the true transition state. Approximately 20% of the putative TSE structures were
      found to have a P(fold) near 0.5, indicating that, although correct TSE
      conformations are populated at the free energy barrier, there is a critical need
      to refine this ensemble. Our simulations indicate that the true TSE conformations
      are compact, with a well-defined central beta sheet, in good agreement with
      previous experimental and theoretical studies. A structured central beta sheet
      was found to be present in a number of pre-TSE conformations, however, indicating
      that this element, although required in the transition state, does not define it
      uniquely. An additional tight cluster of contacts between highly conserved
      residues belonging to the diverging turn and second beta-sheet of the protein
      emerged as being critical elements of the folding nucleus. A number of commonly
      used order parameters to identify the transition state for folding were
      investigated, with the number of native Cbeta contacts displaying the most
      satisfactory correlation with P(fold) values.

PMID- 15982667
TI  - Kinetic partitioning during folding of the p53 DNA binding domain.
AB  - The DNA-binding domain (DBD) of wild-type p53 loses DNA binding activity
      spontaneously at 37 degrees C in vitro, despite being thermodynamically stable at
      this temperature. We test the hypothesis that this property is due to kinetic
      misfolding of DBD. Interrupted folding experiments and chevron analysis show that
      native molecules are formed via four tracks (a-d) under strongly native
      conditions. Folding half-lives of tracks a-d are 7.8 seconds, 50 seconds, 5.3
      minutes and more than five hours, respectively, in 0.3M urea (10 degrees C).
      Approximately equal fractions of molecules fold through each track in zero
      denaturant, but above 2.0M urea approximately 90% fold via track c. A kinetic
      mechanism consisting of two parallel folding channels (fast and slow) is
      proposed. Each channel populates an on-pathway intermediate that can misfold to
      form an aggregation-prone, dead-end species. Track a represents direct folding
      through the fast channel. Track b proceeds through the fast channel but via the
      off-pathway state. Track c corresponds to folding via the slow channel, primarily
      through the off-pathway state. Track d proceeds by way of an even slower,
      uncharacterized route. We postulate that activity loss is caused by partitioning
      to the slower tracks, and that structural unfolding limits this process. In
      support of this view, tumorigenic hot-spot mutants G245S, R249S and R282Q
      accelerate unfolding rates but have no affect on folding kinetics. We suggest
      that these and other destabilizing mutants facilitate loss of p53 function by
      causing DBD to cycle unusually rapidly between folded and unfolded states. A
      significant fraction of DBD molecules become effectively trapped in a non
      functional state with each unfolding-folding cycle.

PMID- 15982668
TI  - Slow assembly and disassembly of lambda Cro repressor dimers.
AB  - Dimers of Cro are required to recognize operator DNA and repress transcription,
      but dimerization is weak compared to DNA binding. Fluorophore-conjugated, single
      cysteine variants of Cro have been used to investigate the equilibria and
      kinetics of dimer assembly. Equilibrium distributions of mixed dimers, monitored
      by fluorescence resonance energy transfer (FRET), confirm that labeled variants
      have equilibrium dimer dissociation constants in the micromolar concentration
      range. Subunit exchange experiments yield first order rate constants for dimer
      dissociation that range from 0.02 s(-1) to 0.04 s(-1). Association rate constants
      calculated from the ratios of dissociation equilibrium and rate constants range
      from 0.7x10(4) M(-1) s(-1) to 3x10(4) M(-1) s(-1), depending on the site of the
      fluorescent label. At nanomolar concentrations of subunits, assembly can be
      driven by addition of DNA. The bimolecular association rate constants measured
      under these conditions are not dramatically enhanced, ranging from 7x10(4) M(-1)
      s(-1) to 9x10(4) M(-1) s(-1). The association rate is second order in protein but
      independent of DNA concentration between 10 nM and 200 nM. The association of
      subunits under native conditions is more than four orders of magnitude slower
      than the fast assembly phase measured previously in refolding experiments, and is
      unaffected by peptidyl-prolyl isomerases. Stabilization of the folded structure
      of the protein by residue substitution in Cro F58W or reduced temperature
      increases the ratio of dimers to monomers and decreases the rate of subunit
      exchange. These data suggest that native monomers have compact structures with
      substantial barriers to unfolding and that unfolded or partially folded monomers
      are the preferred substrates for dimer assembly. Cro binding in vivo may be under
      kinetic rather than thermodynamic control. The slow assembly of Cro dimers
      demonstrated here provides a new perspective on the lysis/lysogeny switch of
      bacteriophage lambda.

PMID- 15982669
TI  - Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal
      muscle: role of IRS phosphorylation.
AB  - Hyperglycemia, glucose intolerance and elevated insulin levels frequently occur
      in burned patients; however, the mechanism(s) for this insulin resistance has not
      been fully elucidated. One possible mechanism could involve alterations in the
      phosphorylation of serine 307 of the insulin receptor substrate-1 (IRS-1) via
      activation of stress kinase enzymes, including SAPK/JNK. In the present study we
      examined the time course of the effect of burn injury to mice on: levels of IRS-1
      protein, phosphorylation of serine 307 of IRS-1, SAPK/JNK kinase levels and
      activity and Akt kinase activity in hind limb skeletal muscle. Burn injury
      produced a reduction in hind limb muscle mass 24 h after injury, and, which
      persisted for 168 h. At 24 h after injury, there was a dramatic ( approximately 9
      fold) increase in phosphorylation of IRS-1 serine 307 followed by a more moderate
      elevation thereafter. Total IRS-1 protein was slightly elevated at 24 h after
      injury and decreased to levels below sham treated animals at the later times.
      Burn injury did not appear to change total SAPK/JNK protein content, however,
      enzyme activity was increased for 7 days after injury. Akt kinase activity was
      decreased in skeletal muscle following burn injury; providing a biochemical basis
      for burn-induced insulin resistance. These findings are consistent with the
      hypothesis that burn-induced insulin resistance may be related, at least in part,
      to alterations in the phosphorylation of key proteins in the insulin signaling
      cascade, including IRS-1, and that changes in stress kinases, such as SAPK/JNK
      produced by burn injury, may be responsible for these changes in phosphorylation.

PMID- 15982670
TI  - Myricetin inhibits the induction of anti-Fas IgM-, tumor necrosis factor-alpha-
      and interleukin-1beta-mediated apoptosis by Fas pathway inhibition in human
      osteoblastic cell line MG-63.
AB  - The survival of osteoblast cells is one of the determinants of the development of
      osteoporosis in patients with inflamed synovium, such as in rheumatoid arthritis
      (RA). By means of alkaline phosphatase (ALP) activity and osteocalcin ELISA
      assay, I have shown that myricetin exhibits a significant induction of
      differentiation in the human osteoblast-like cell line MG-63. In addition, I also
      assessed whether myricetin affects inflammatory cytokines-mediated apoptosis in
      osteoblast cells. TNF-alpha or IL-1beta enhances apoptotic DNA fragmentation in
      anti-Fas IgM-treated MG-63 cells by increasing Fas receptor expression. However,
      TNF-alpha or IL-1beta treatment alone does not induce apoptosis. Treatment of MG
      63 cells with myricetin not only inhibited anti-Fas IgM-induced apoptosis, but
      also blocked the synergetic effect of anti-Fas IgM with TNF-alpha or IL-1beta on
      cell death. The apoptotic inhibition of myricetin is associated with inhibition
      of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP
      expression, resulting in a decrease of caspase-8 and caspase-3 activation. These
      results indicate a potential use of myricetin in preventing osteoporosis by
      inhibiting inflammatory cytokines-mediated apoptosis in osteoblast cells.

PMID- 15982671
TI  - Cranberries inhibit LDL oxidation and induce LDL receptor expression in
      hepatocytes.
AB  - Cardiovascular disease (CVD) is the leading cause of death in most industrialized
      countries. Cranberries were evaluated for their potential roles in dietary
      prevention of CVD. Cranberry extracts were found to have potent antioxidant
      capacity preventing in vitro LDL oxidation with increasing delay and suppression
      of LDL oxidation in a dose-dependent manner. The antioxidant activity of 100 g
      cranberries against LDL oxidation was equivalent to 1000 mg vitamin C or 3700 mg
      vitamin E. Cranberry extracts also significantly induced expression of hepatic
      LDL receptors and increased intracellular uptake of cholesterol in HepG2 cells in
      vitro in a dose-dependent manner. This suggests that cranberries could enhance
      clearance of excessive plasma cholesterol in circulation. We propose that
      additive or synergistic effects of phytochemicals in cranberries are responsible
      for the inhibition of LDL oxidation, the induced expression of LDL receptors, and
      the increased uptake of cholesterol in hepatocytes.

PMID- 15982672
TI  - Eastern Pacific Ocean source of Northwestern Hawaiian Islands marine debris
      supported by errant fish aggregating device.

PMID- 15982673
TI  - Big science in the seas.

PMID- 15982674
TI  - Controllability of non-linear biochemical systems.
AB  - Mathematical methods of biochemical pathway analysis are rapidly maturing to a
      point where it is possible to provide objective rationale for the natural design
      of metabolic systems and where it is becoming feasible to manipulate these
      systems based on model predictions, for instance, with the goal of optimizing the
      yield of a desired microbial product. So far, theory-based metabolic optimization
      techniques have mostly been applied to steady-state conditions or the
      minimization of transition time, using either linear stoichiometric models or
      fully kinetic models within biochemical systems theory (BST). This article
      addresses the related problem of controllability, where the task is to steer a
      non-linear biochemical system, within a given time period, from an initial state
      to some target state, which may or may not be a steady state. For this purpose,
      BST models in S-system form are transformed into affine non-linear control
      systems, which are subjected to an exact feedback linearization that permits
      controllability through independent variables. The method is exemplified with a
      small glycolytic-glycogenolytic pathway that had been analyzed previously by
      several other authors in different contexts.

PMID- 15982675
TI  - Population dynamics models in plant-insect herbivore-pesticide interactions.
AB  - We consider several population dynamics models in investigating data from
      controlled experiments with aphids in broccoli patches surrounded by different
      margin types (bare or weedy ground) and three levels of insecticide spray (no,
      light, or heavy spray). We carry out parameter estimation computations along with
      statistical analysis to compare autonomous versus non-autonomous model dynamics.
      We conclude with a brief discussion of some not-so-subtle pitfalls that can arise
      when using quantitative measures of model fit-to-data to make biological
      inferences as well as offer a positive example of how one might combine a priori
      biological hypothesis and intuition with rather sophisticated (from a field
      biology viewpoint) mathematical methodologies to suggest synergisms.

PMID- 15982676
TI  - The utility of genetically altered mouse models for cancer research.

PMID- 15982677
TI  - Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: evidence
      consistent with a glycidamide-mediated effect.
AB  - Acrylamide, an animal carcinogen and germ cell mutagen present at low (ppm)
      levels in heated carbohydrate-containing foodstuffs, is oxidized by cytochrome
      P4502E1 (CYP2E1) to the epoxide glycidamide, which is believed to be responsible
      for the mutagenic and carcinogenic activity of acrylamide. We recently reported a
      comparison of the effects of acrylamide on the genetic integrity of germ cells of
      male wild-type and CYP2E1-null mice [B.I. Ghanayem, K.L. Witt, L. El-Hadri, U.
      Hoffler, G.E. Kissling, M.D. Shelby, J.B. Bishop, Comparison of germ-cell
      mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide:
      evidence supporting a glycidamide-mediated effect, Biol. Reprod. 72 (2005) 157
      163]. In those experiments, dose-related increases in dominant lethal mutations
      were detected in uterine contents of female mice mated to acrylamide-treated wild
      type males but not CYP2E1-null males, clearly implicating CYP2E1-mediated
      formation of glycidamide in the induction of genetic damage in male germ cells.
      We hypothesized that acrylamide-induced somatic cell damage is also caused by
      glycidamide. Therefore, to examine this hypothesis, female wild-type and CYP2E1
      null mice were administered acrylamide (0, 25, 50mg/kg) by intraperitoneal
      injection once daily for 5 consecutive days. Twenty-four hours after the final
      treatment, blood and tissue samples were collected. Erythrocyte micronucleus
      frequencies were determined using flow cytometry and DNA damage was assessed in
      leukocytes, liver, and lung using the alkaline (pH>13) single cell gel
      electrophoresis (Comet) assay. Results were consistent with the earlier
      observations in male germ cells: significant dose-related increases in
      micronucleated erythrocytes and DNA damage in somatic cells were induced in
      acrylamide-treated wild-type but not in the CYP2E1-null mice. These results
      support the hypothesis that genetic damage in somatic and germ cells of mice
      treated with acrylamide is dependent upon metabolism of the parent compound by
      CYP2E1. This dependency on metabolism has implications for the assessment of
      human risks resulting from occupational or dietary exposure to acrylamide. CYP2E1
      polymorphisms and variability in CYP2E1 activity associated with, for example,
      diabetes, obesity, starvation, and alcohol consumption, may result in altered
      metabolic efficiencies leading to differential susceptibilities to acrylamide
      toxicities in humans.

PMID- 15982678
TI  - Vocal amusia in a professional tango singer due to a right superior temporal
      cortex infarction.
AB  - We describe the psychophysical features of vocal amusia in a professional tango
      singer caused by an infarction mainly involving the superior temporal cortex of
      the right hemisphere. The lesion also extended to the supramarginal gyrus, the
      posterior aspect of the postcentral gyrus and the posterior insula. She presented
      with impairment of musical perception that was especially pronounced in
      discriminating timbre and loudness but also in discriminating pitch, and a
      severely impaired ability to reproduce the pitch just presented. In contrast,
      language and motor disturbances were almost entirely absent. By comparing her pre
      and post-stroke singing, we were able to show that her singing after the stroke
      lacked the fine control of the subtle stress and pitch changes that characterized
      her pre-stroke singing. Such impairment could not be explained by the impairment
      of pitch perception. The findings suggest that damage to the right
      temporoparietal cortex is enough to produce both perceptive and expressive
      deficits in music.

PMID- 15982679
TI  - Systematics and health effects of chemically distinct tannins in medicinal
      plants.
AB  - The research began with an investigation of tannins from traditional medicinal
      plants and resulted in isolation and structure determination of hundreds of
      ellagitannins and dehydroellagitannins, as well as their oligomers and oxidized
      derivatives with various structures specific to each plant species. These
      polyphenols have been classified according to the stage of oxidative structural
      transformation and oligomerization, into types I-IV and I+ to IV+, etc. Parallels
      were found between their oxidative transformations and plant evolution. They were
      also classified by the linkage units between the monomers, into DOG, GOD, GOG and
      DOGOD types (D=Diphenoyl, G=Galloyl, O=Oxygen), etc. Besides their fundamental
      activities, e.g., reduction and anti-peroxidation properties, remarkable
      biological and pharmacological activities of various potencies have also been
      found, including, amongst others, inhibition of lipid-peroxidation, mutagenicity
      of carcinogens and tumor promotion, host-mediated antitumor effects specific to
      particular tannin structures, antiviral activity and potentiation of
      antibacterial activity.

PMID- 15982680
TI  - Changes in blood and milk lymphocyte sub-populations during acute and chronic
      phases of Staphylococcus aureus induced bovine mastitis.
AB  - Staphylococcus aureus (S. aureus) often causes long-lasting chronic sub-clinical
      udder infections in dairy cows. To investigate if this can be due to a negative
      impact of S. aureus on lymphocytes important for the immune defence, alterations
      in proportions and expression intensity of CD4+, CD8+, WC1+, B and IL-2R+
      lymphocytes was studied in blood and milk, as S. aureus mastitis developed from
      acute clinical to chronic sub-clinical form. Six healthy dairy cows were
      inoculated with S. aureus in one udder quarter per cow, and one quarter per cow
      acted as an uninfected control. Blood samples, and milk samples from infected and
      non-infected quarters were collected before infection and for five weeks after
      infection. All infected quarters developed acute clinical mastitis, of which five
      turned into chronic sub-clinical mastitis. In infected quarters, the proportions
      of all lymphocyte sub-sets, except WC1+ cells, differed in acute phase compared
      to pre-infection, while the dominant finding in the chronic phase was increased
      expression intensities per cell. An impact on blood lymphocytes and milk
      lymphocytes in non-infected quarters also occurred, mainly during the chronic
      phase. The most prominent finding was the increased proportion and expression of
      B-lymphocytes in blood, infected and non-infected quarters during chronic sub
      clinical mastitis. As S. aureus can invade and survive intracellularly, a
      preferential stimulation of B-cells, suggesting development of a humoral
      response, may not be sufficient to eliminate intracellular bacteria, which could
      explain the persistence of the infection.

PMID- 15982682
TI  - The stress response in gametes and embryos after paternal chemical exposures.
AB  - There is increasing concern that paternal exposure to toxic chemicals impacts
      negatively on progeny outcome. Exposure of male rats to a model male-mediated
      developmental toxicant and anticancer alkylating agent, cyclophosphamide,
      resulted in increased pre- and post-implantation loss, as well as in
      malformations. We hypothesize that the stage specificity of the effects of
      paternal cyclophosphamide exposure on progeny depends on the ability of germ
      cells to respond to stress, repair DNA or undergo apoptosis. Acute high dose
      exposure of male rats to cyclophosphamide increased the expression of heat shock
      proteins and DNA repair genes, predominantly in round spermatids. In contrast,
      chronic low dose treatment dramatically decreased the expression of stress
      response genes in pachytene spermatocytes and round spermatids, but not in
      elongated spermatids; this reduced ability to respond to stress may allow damage
      to accumulate, resulting in altered sperm function. Increased DNA damage was
      maximal 3 weeks after drug exposure, during spermiogenesis, a key point in sperm
      chromatin remodelling. Drug exposure for 9 weeks increased the frequency of
      spermatozoa with chromosome 4 disomy and nullisomy. DNA damage found in
      cyclophosphamide-exposed spermatozoa was imparted to the newly fertilized zygote.
      Drug-exposed spermatozoa decondensed more rapidly than control spermatozoa and
      male pronuclear formation was earlier. RNA synthesis was higher in 1-cell embryos
      sired by drug-treated fathers than in controls. Significantly, the profile of
      gene expression was altered in embryos sired by drug-treated males as early as
      the 1-cell stage. Thus, exposure of male rats to cyclophosphamide altered male
      germ cell quality with a consequent temporal and spatial disruption of the
      zygotic genome activation.

PMID- 15982681
TI  - Biomarkers of drug-induced vascular injury.
AB  - In pre-clinical safety studies, drug-induced vascular injury is an issue of
      concern because there are no obvious diagnostic markers for pre-clinical or
      clinical monitoring and there is an intellectual gap in our understanding of the
      pathogenesis of this lesion. While vasodilatation and increased shear stress
      appear to play a role, the exact mechanism(s) of injury to the primary targets,
      smooth muscle and endothelial cells are unknown. However, evaluation of novel
      markers for potential clinical monitoring with a mechanistic underpinning would
      add value in risk assessment and management. This mini review focuses on the
      progress to identify diagnostic markers of drug-induced vascular injury. Von
      Willebrand factor (vWF), released upon perturbation of endothelial cells, is
      transiently increased in plasma prior to morphological evidence of damage in dogs
      or rats treated with vascular toxicants. Therefore, vWF might be a predictive
      biomarker of vascular injury. However, vWF is not an appropriate biomarker of
      lesion progression or severity since levels return to baseline values when there
      is morphological evidence of injury. A potential mechanistically linked biomarker
      of vascular injury is caveolin-1. Expression of this protein, localized primarily
      to smooth muscle and endothelial cells, decreases with the onset of vascular
      damage. Since vascular injury involves multiple mediators and cell types,
      evaluation of a panel rather than a single biomarker may be more useful in
      monitoring early and severe progressive vascular injury.

PMID- 15982683
TI  - Detoxification of organophosphate nerve agents by bacterial phosphotriesterase.
AB  - Organophosphates have been widely used as insecticides and chemical warfare
      agents. The health risks associated with these agents have necessitated the need
      for better detoxification and bioremediation tools. Bacterial enzymes capable of
      hydrolyzing the lethal organophosphate nerve agents are of special interest.
      Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta
      displays a significant rate enhancement and substrate promiscuity for the
      hydrolysis of organophosphate triesters. Directed evolution and rational redesign
      of the active site of PTE have led to the identification of new variants with
      enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of
      organophosphate neurotoxins. PTE has been utilized to protect against
      organophosphate poisoning in vivo. Biotechnological applications of PTE for
      detection and decontamination of insecticides and chemical warfare agents are
      developing into useful tools. In this review, the catalytic properties and
      potential applications of this remarkable enzyme are discussed.

PMID- 15982684
TI  - Alternatives to animal experimentation: the regulatory background.
AB  - The framework, in which alternatives to animal experiments can be developed,
      standardized, respectively formally validated, has to be seen in a global
      context. The ever increasing demand of testing for hazard and risk assessment in
      health and environment, exemplified by the EU REACH program, subsequently
      triggers laboratory animal testing. This holds especially true, if no valid
      alternative methods agreed to by the regulatory authorities and the scientific
      community are available. At least for regulatory toxicity testing, the global
      frame and network are given by institutions such as OECD, ICH, and alike.
      However, due to the necessity of global consent of states, organizations, and
      stakeholders, the time gap between availability of a novel alternative test
      method and its final acceptance by authorities and implementation thereafter is
      widening. The lack of new technologies or opportunities for alternative method
      application such as, for example, the broad use of transgenic animals for
      refinement of existing tests, adds to the problem. The bare existence of certain
      in vivo tests increases also the gap between public demands for testing versus
      availability of alternative tests. Industries operating on a worldwide basis
      support the alternative test development in their respective area of research and
      operational business. However, a more coordinating approach such as that of the
      ecopa-organization (European Consensus Platform on Alternatives) is needed to
      exploit the existing possibilities within the current regulatory framework. This
      will speed up the process of acceptance and challenge the political world to feel
      responsible for the sequels of their demanding more testing, that is, by funding
      alternative method development in academia and industry.

PMID- 15982685
TI  - Drug-induced oxidative stress in rat liver from a toxicogenomics perspective.
AB  - Macrophage activators (MA), peroxisome proliferators (PP), and oxidative
      stressors/reactive metabolites (OS/RM) all produce oxidative stress and
      hepatotoxicity in rats. However, these three classes of hepatotoxicants give
      three distinct gene transcriptional profiles on cDNA microarrays, an indication
      that rat hepatocytes respond/adapt quite differently to these three classes of
      oxidative stressors. The differential gene responses largely reflect differential
      activation of transcription factors: MA activate Stat-3 and NFkB, PP activate
      PPARa, and OS/RM activate Nrf2. We have used gene signature profiles for each of
      these three classes of hepatotoxicants to categorize over 100 paradigm (and 50+
      in-house proprietary) compounds as to their oxidative stress potential in rat
      liver. In addition to a role for microarrays in predictive toxicology, analyses
      of small subsets of these signature profiles, genes within a specific pathway, or
      even single genes often provide important insights into possible mechanisms
      involved in the toxicities of these compounds.

PMID- 15982686
TI  - What determines the acceptability of genetically modified food that can improve
      human nutrition?
AB  - It has been predicted that by 2025 there will be an annual shortfall of cereals
      for feeding the human population of 68.5 million tones. One possible solution is
      the use of genetically modified (GM) crops, which are already grown extensively
      (59 million ha of GM crops were planted in 2002) in the USA, South America,
      Africa and China. Nevertheless, there is considerable disagreement about the
      advisability of using such crops, particularly in Europe. Obviously, the safety
      of the food derived from the GM crops is a primary consideration. Safety
      assessment relies on establishing that the food is substantially equivalent to
      its non-GM counterpart and specific testing for allergenicity of proteins and
      toxicity of metabolites and the whole food. There appears to be international
      agreement on the principles of safety assessment. Safety to the environment is
      equally important, but will not be covered in this presentation. The public's
      perception of the risk of new technology is critical to its acceptance.
      Perception of risk, in turn, depends on the credibility of the source of the
      information and trust in the regulatory process. In many countries, the public
      appears to have lost its trust in the scientists and government dealing with GM
      food, making the acceptability of GM crops uncertain. Of equal importance are the
      socio-economic factors that impinge on the viability of GM produce. These include
      intellectual property protection, trade liberalization (through subsidy and
      tariff barriers in developed countries) and the intensity of bio safety
      regulations. The socio-economic interests of developed and developing countries
      may diverge and may even be contradictory in any one country. Acceptance of GM
      crops will thus depend on detailed issues surrounding particular crops and
      economies.

PMID- 15982687
TI  - Past challenges faced: an overview of current educational activities of IUTOX.
AB  - Over the past decade, educational programmes have been the main focus of the
      activities of the International Union of Toxicology (IUTOX). The IUTOX
      educational programmes are dynamic and have been growing in scope and frequency
      each year. It is envisaged that this growth will continue with guidance from our
      member societies and the continuing support of our sponsors. Presently, IUTOX is
      engaged in the following educational programmes: (1) International congresses
      that provide the opportunity for direct communication of current toxicological
      information. Fellowships are sponsored to facilitate attendance at these
      congresses for toxicologists in need. (2) Workshops that permit interaction on a
      more localised level of topics of more regional interest. Workshops have served
      to help stimulate formation of toxicology societies by bringing together
      sufficient scientists to facilitate these discussions. (3) Continuing educational
      (CE) programmes at member society meetings. Topics are prioritized based on input
      received from the local societies. Programmes often are those from CE courses
      given at meetings, such as conferences of the US Society of Toxicology (US SOT)
      and EUROTOX from the previous year. (4) Biennial Risk Assessment Summer School
      (RASS), an intensive week-long interaction between senior toxicologists who serve
      as faculty with attendees providing individual training. (5) Dissemination of
      donated printed toxicological books from publishers and syllabi from continuing
      education courses to regional locations. (6) Web-based interactive training
      programmes in regions where formal toxicological educational programmes are
      limited or lacking. (7) Preparation and distribution of monographs on selected
      topics of very current interest. Monographs on environmental oestrogens and
      genetically-modified foods have been published. The recent activities in each of
      these programmes are reviewed in this paper.

PMID- 15982688
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP)
      expression and invasion in A2058 melanoma cells.
AB  - There has been a 34% increase in melanoma related mortality in the United States
      from 1973 to 1992. Although few successful treatments for malignant melanoma
      exist, it is known that genetic susceptibility and environmental factors
      contribute to the initiation and progression of melanoma. Excessive UV exposure
      is considered the main etiological factor in melanoma initiation, however,
      epidemiological and experimental evidence suggests that exposure to environmental
      carcinogens contribute to melanoma. We propose that exposure to environmental
      chemicals that activate the aryl hydrocarbon receptor pathway contribute to
      melanoma progression, specifically through stimulation of the expression and
      activity of the matrix metalloproteinases (MMPs). Therefore, we investigated the
      effect of AhR activation on normal human melanocytes and several melanoma cell
      lines. The data presented here demonstrate that normal melanocytes and melanoma
      cells express the AhR and Arnt and are responsive to activation by TCDD.
      Furthermore, activation of this pathway in transformed melanoma cells (A2058)
      results in increased expression and activity of MMP-1, MMP-2 and MMP-9, as well
      as increased invasion using in vitro invasion assays. Furthermore, TCDD-induced
      expression of the MMP-1 promoter in melanoma cells appears to require different
      elements than those required in untransformed cells, indicating that this pathway
      may have multiple mechanisms for activation of MMP expression.

PMID- 15982689
TI  - Recent developments in preclinical toxicological pathology.
AB  - In the late nineteenth century, microscopists developed a quaint method for
      examining the fine structure of biological specimens: paraffin embedding and
      staining with hematoxylin and eosin. This ancient technology is here to stay for
      the foreseeable future, because it can and does reveal the truth about biological
      processes. However, the role of pathology is developing with ever greater world
      wide interaction between pathologists, and better communication and agreeing of
      international standards. Furthermore, recent techniques including
      immunohistochemistry, electron microscopy and image analysis complement the
      traditional tried and tested tools. There is also in toxicologic pathology a
      willingness to use pathology methods and skills in new contexts, drug discovery
      in particular. But even in these days of genetic modification, proteomics and
      high throughput screening, pathologists continue to rely on dyes extracted from a
      Central American logwood used in Mexico before the Spanish invasion in 1520.

PMID- 15982690
TI  - Current status and burning issues in immunotoxicity testing of drugs.
AB  - Besides pathology endpoints, additional immune function endpoints have been
      included in the Note for Guidance on Repeated Dose Toxicity by the European Union
      (July 2001), which concern the analysis of antibody responses to a T-cell
      dependent antigen. Guidance papers of other regulatory authorities are published
      as well. The main issue is the need for functional immunotoxicity testing to
      detect unintended immunosuppression. The International Conference on
      Harmonization (ICH) has surveyed studies from the files of the pharmaceutical
      industry to find the proportion of compounds that can be detected by additional
      immunotoxicity testing. Preliminary analysis shows that 10-15% of the compounds
      in the survey only react positively to the additional tests. More data are
      requested from the pharmaceutical industry. The Expert Working Group of the ICH
      has decided to choose a cause-for-concern approach to immunotoxicity rather than
      a routine-screening approach. The causes for concern are to be defined during ICH
      negotiations.

PMID- 15982691
TI  - Research perspectives for pre-screening alternatives to animal experimentation:
      on the relevance of cytotoxicity measurements, barrier passage determinations and
      high throughput screening in vitro to select potentially hazardous compounds in
      large sets of chemicals.
AB  - The MEIC study revealed a high predictivity of in vitro cytotoxicity data for
      human acute systemic toxicity. The idea, put forward by several authors, that
      compounds that show high cytotoxicity should not need further testing for
      confirmation but could be assumed toxic also in vivo provides a convenient
      concept for the selection of the most relevant compounds for further studies in
      large sets of chemicals, as in the REACH program. The automated techniques
      applied in high throughput screening (HTS) by the pharmaceutical and biotech
      industries to select hits in extensive compound collections represent an
      opportunity to significantly increase the capacity of cytotoxicity testing.
      Furthermore, it has been suggested that a combination of cytotoxicity data and
      some basic biokinetic information would greatly improve the accuracy in the
      extrapolation from in vitro to in vivo and thus make it possible to identify
      additional toxic compounds that might have escaped in the initial screen. Such
      information, which can be obtained in a medium throughput screening mode (MTS),
      includes biotransformation, absorption and some aspects of distribution. The
      measurement of the net flux of a compound over a cellular barrier, as the one
      formed in culture by human Caco-2 cells, gives useful, but limited, information
      on both gut absorption and blood-brain barrier penetration. The test procedures
      discussed here, as well as other supplementary in vitro tests, cannot always
      easily be described in terms of animal-based test replacements. In those
      instances, the necessary test validation cannot be carried out using animal
      reference data, and prediction models may have to be adapted to new ideas.
      Consequently, concepts of prospective validation to supplement the now well
      established retrospective validation have to be developed.

PMID- 15982692
TI  - Distance learning in toxicology: resident and remote; Scotland, IPCS, IUPAC, and
      the world.
AB  - Globally, very few college or university chemistry courses incorporate toxicology
      although public perception of chemicals and the chemical industry as threats to
      health and the environment has had an adverse effect on chemistry and on the use
      of its products. The International Union for Pure and Applied Chemistry (IUPAC)
      through its Commission on Toxicology recognized this and, with the support of the
      Committee on the Teaching of Chemistry has used the IUPAC web site to promote
      distance learning in toxicology for chemists. After preparation of a thoroughly
      refereed consensus Glossary of Terms for Chemists of Terms Used in Toxicology, a
      textbook Fundamental Toxicology for Chemists and a set of educational modules
      entitled Essential Toxicology were compiled and put through the normal thorough
      review procedure of IUPAC before being approved by the organization. There is now
      an additional Glossary of Terms Used in Toxicokinetics. The modules are freely
      downloadable in Adobe PDF format and are designed to be used both by educators
      and by students. Educators are asked to select whatever is appropriate to their
      students and to use the material as they wish, adding content specifically
      relevant to their circumstances. For self-study, the web modules have self
      assessment questions and model answers. Currently the original Glossary for
      Chemists of Terms Used in Toxicology is being revised and it is expected that
      this will lead to further developments. The currently available components of the
      IUPAC programme may be accessed through the IUPAC website at the Subcommittee on
      Toxicology and Risk Assessment page:
      http://www.iupac.org/divisions/VII/VII.C.2/index.html.

PMID- 15982693
TI  - Comprehensive non-clinical respiratory evaluation of promising new drugs.
AB  - The need to evaluate the potential for new drugs to produce adverse effects on
      respiratory function in non-clinical safety assessment is based on the known
      effects of drugs from a variety of pharmacological/therapeutic classes on the
      respiratory system, the life-threatening consequences of respiratory dysfunction,
      and compliance with world-wide regulatory safety guidelines. The objective of
      this article is to provide a brief overview of the functional disorders of the
      respiratory system and to present the strategy and techniques considered to be
      most appropriate for detecting and characterizing drug-induced respiratory
      disorders in non-clinical safety studies.

PMID- 15982694
TI  - Evaluation and interpretation of maternal toxicity in Segment II studies: issues,
      some answers, and data needs.
AB  - Biologically rational regulatory policies with regards to developmental toxicity
      are often based on the extrapolation of standard laboratory rodent bioassay
      results to the human population. Significantly contributing to the difficulty of
      this task is the possibility that general toxic effects on the maternal organism
      may affect the developing conceptus. This review examines maternal factors which
      may bear directly or indirectly upon developmental outcome, with emphasis on
      those of greatest relevance to the hazard assessment process. Standard teratology
      testing protocols call for top dosage levels that induce overt maternal toxicity,
      and the developmental effects of this toxicity (both alone, and with concurrent
      embryo/fetal insult) continue to present regulators with considerable
      interpretive difficulties. In response to these problems, there have been both
      research and literature review efforts dealing with the relationship of maternal
      and developmental toxicity. Maternally mediated developmental toxicity occurs
      with a number of agents, and toxicant-induced alterations in maternal physiology
      may affect the conceptus at dosages not causing overt maternal toxicity. Relevant
      studies are reviewed here, and suggestions for avenues of future research are
      offered including the identification of any syndromes of developmental effects
      occurring at maternally toxic levels irrespective of the causative agent, and
      experimental approaches for the characterization of maternal toxicity.

PMID- 15982695
TI  - Inter-individual susceptibility to environmental toxicants--a current assessment.
AB  - Virtually all diseases have an environmental component. The two most important
      factors affecting your unique risk of an environmental disease (toxicity or
      cancer) are (a) your exposure to the environmental agent and (b) your genes.
      Epidemiologists have found ways to calculate inter-individual risk--if the
      exposure to environmental agents is sufficiently high and can be documented
      (e.g., years of cigarette smoking, taking prescribed drugs, drinking alcohol, or
      exposure to radon or other radioactive material, etc.). If the dose of
      environmental agents is lower and more ambiguous (e.g., exposure to chemicals on
      the job, herbicides sprayed on a golf course, outdoor or indoor air pollution,
      endocrine disruptors in cans of food, living near a toxic waste dump site, etc.),
      however, calculations of inter-individual risk become much more difficult. Highly
      accurate DNA tests for genetic susceptibility to toxicity and cancer have been
      sought in order to identify individuals at increased risk; this type of research
      represents the leading edge of phenotype-genotype association studies and is the
      major goal of most public health and preventive medicine programs. The task,
      however, has turned out to be far more challenging than anticipated. The major
      stumbling block has been the difficulty in determining an unequivocal phenotype
      or an unequivocal genotype. We were quite optimistic 5-10 years ago that this
      would be easy, but now we are beginning to appreciate how difficult it is to
      determine an unequivocal phenotype or genotype with certainty. For many reasons
      set forth in this overview, it appears that DNA testing alone, to predict and
      prevent environmental disease on an individual basis, may be virtually impossible
      with current knowledge and technologies and will require novel insights before
      major practical applications will evolve.

PMID- 15982696
TI  - Latin America's present and future challenges in toxicology education.
AB  - Industrialization that Latin America has experienced during the past 50 years,
      the increase of population and the growth of chemical-related industries has
      generated a variety of environmental problems that must be addressed. After
      assessing these profound changes, greater emphasis should be placed on the study
      of environmental health and toxicology. Latin American countries face many
      problems that are common to other developing nations. Therefore, there is a
      demand for safety assessment and regulatory control of chemicals that create a
      need for increasing numbers of toxicologists. To meet this demand, educational
      programs in toxicology have to be designed. This paper utilizes a consultation
      questionnaire that includes toxicology-network members, scientists and
      educational institutions where toxicology is taught. An analysis of the
      information collected is made, with an emphasis on what we currently lack and on
      future challenges for toxicology professionals. Although the response from the
      study institutions was 65% (13 countries out of 20), the paper aims to assess the
      present situation of toxicology. The convenience for a certification/recognition
      for toxicologists is also evaluated. Action needs to be taken to promote
      scientific development based on regional specific needs that require increasing
      at the number of toxicology programs, and promoting of cooperation between
      academics and researchers. Among the limitations we have are the variability of
      curricula, objectives and priorities. The increasing globalization of markets and
      regulations requires the harmonization of graduate/postgraduate programs to
      ensure that risk assessment and management are dealt with uniformly. Cooperation
      among our countries and international assistance should play a more prominent
      role in the promotion of regional integration and the more efficient utilization
      of international experience in defining educational policies.

PMID- 15982697
TI  - Umbilical cord cell banking--implications for the future.
AB  - The first successful cord cell transplant to a sibling with Fanconi's anaemia
      took place 15 years ago. This proven utility of cord blood led to the
      establishment of cord blood banks both private and public and there are now
      nearly 100 cord blood banks worldwide. It is estimated that over 200,000 cord
      blood units (CBU) are held by the private sector and over 160,000 CBU are
      registered with the largest public cord blood registry. There is a tension
      between private cord blood banks, which store CBU for autologous or family use,
      and public banks, which store CBU for unrelated use and the ethics of private
      cord blood storage has been questioned. But more general ethical questions also
      arise regarding ownership, consent, confidentiality, costs and quality standards
      and patenting. In looking at these ethical issues one also needs to look at
      potential future use of cord blood stem cells. Up until now cord cells have
      principally been used in the treatment of paediatric blood and immune disorders.
      Improvements in cell expansion technology will make CBU more appropriate also for
      treating adults with such disorders. However, it has also been demonstrated that
      cord blood stem cells have the capacity to differentiate into other types of
      cells, neuronal, bone, epithelial and muscle which would have a future role to
      play in cell therapy and regenerative medicine.

PMID- 15982698
TI  - Nonlinearity and thresholds in dose-response relationships for carcinogenicity
      due to sampling variation, logarithmic dose scaling, or small differences in
      individual susceptibility.
AB  - Nonlinear and threshold-like shapes of dose-response curves are often observed in
      tests for carcinogenicity. Here, we present three examples where an apparent
      threshold is spurious and can be misleading for low dose extrapolation and human
      cancer risk assessment. Case #1: For experiments that are not replicated, such as
      rodent bioassays for carcinogenicity, random variation can lead to
      misinterpretation of the result. This situation was simulated by 20 random
      binomial samplings of 50 animals per group, assuming a true linear dose response
      from 5% to 25% tumor incidence at arbitrary dose levels 0, 0.5, 1, 2, and 4.
      Linearity was suggested only by 8 of the 20 simulations. Four simulations did not
      reveal the carcinogenicity at all. Three exhibited thresholds, two showed a
      nonmonotonic behavior with a decrease at low dose, followed by a significant
      increase at high dose ("hormesis"). Case #2: Logarithmic representation of the
      dose axis transforms a straight line into a sublinear (up-bent) curve, which can
      be misinterpreted to indicate a threshold. This is most pronounced if the dose
      scale includes a wide low dose range. Linear regression of net tumor incidences
      and intersection with the dose axis results in an apparent threshold, even with
      an underlying true linear dose-incidence relationship. Case #3: Nonlinear shapes
      of dose-cancer incidence curves are rarely seen with epidemiological data in
      humans. The discrepancy to data in rodents may in part be explained by a wider
      span of individual susceptibilities for tumor induction in humans due to more
      diverse genetic background and modulation by co-carcinogenic lifestyle factors.
      Linear extrapolation of a human cancer risk could therefore be appropriate even
      if animal bioassays show nonlinearity.

PMID- 15982699
TI  - Use of two detection methods to discriminate ciguatoxins from brevetoxins:
      application to great barracuda from Florida Keys.
AB  - In Florida (USA), numerous cases of human ciguatera fish poisoning, as well as
      neurotoxic shellfish poisoning following consumption of local seafood products,
      have been reported. By using in parallel, the sodium channel receptor binding
      assay (RBA), and the ouabain/veratridine-dependent cytotoxicity assay (N2A
      assay), we established criteria to identify, detect, and quantify ciguatoxins in
      fish extracts, with a brevetoxin as internal standard. Results showed that the
      Caribbean ciguatoxin C-CTX-1 exhibited an 8-fold higher potency in the RBA than
      brevetoxins and, a 440 and 2300-fold higher potency in the N2A assay than PbTx-1
      and PbTx-3, respectively. Moreover, a sensitivity comparison between assays
      revealed that the N2A assay was more sensitive (12-fold) for ciguatoxin analysis,
      whereas the RBA was more sensitive (3-24-fold) for brevetoxins analysis. Based on
      the relative potency between toxins and the opposite sensitivity of both assays
      we have used the RBA and the N2A assay to screen great barracuda (Sphyraena
      barracuda) collected from the Florida Keys for ciguatoxins and brevetoxins. Fish
      extract analysis showed a sodium channel-dependent activity consistent with the
      presence of ciguatoxins, and not brevetoxins. Among 40 barracudas analyzed, 60%
      contained ciguatoxin levels in their liver measurable by the N2A assay with the
      most toxic fish containing 2.1ppb C-CTX-1 equivalents.

PMID- 15982700
TI  - New linear polyamine derivatives in spider venoms.
AB  - Linear free polyamines were characterized in the venom of the spiders Agelenopsis
      aperta, Hololena curta, and Paracoelotes birulai by RP-HPLC coupled to mass
      spectrometry. The several linear polyamines found were tetramine, pentamine, and
      hexamine derivatives. Some of these natural products were identified as N
      hydroxylated, guanidylated, or acetylated compounds. In addition, the
      biosynthetical pathway leading to the formation of acylpolyamines in spider
      venoms is discussed.

PMID- 15982701
TI  - Use of formic acid as reducing agent for application in catalytic reduction of
      nitrate in water.
AB  - The reduction of nitrate in nitrogen using bimetallic palladium tin catalysts and
      hydrogen is an interesting process for water treatment. The aim of the present
      study is to use formic acid (FA) as a reducing agent and a pH buffer in order to
      substitute the mixture of hydrogen and carbon dioxide. The catalytic performances
      of a palladium tin catalyst supported on silica were evaluated in the presence of
      FA, as a function of the initial acid concentration and of the gas phase (N(2),
      CO(2), or H(2)). Results were compared to those obtained with hydrogen in the
      presence of carbon dioxide. Similar mechanisms seem to explain the identical
      catalytic performances observed with these two reducing agents.

PMID- 15982702
TI  - Sorption of Cr(VI) from dilute solutions and wastewater by live and pretreated
      biomass of Aspergillus flavus.
AB  - Sorption of Cr(VI) was carried out from dilute solutions using live and
      pretreated biomass in a batch mode. Effects of agitation time, adsorbent dosage
      and pH were examined. The autoclaved biomass that showed maximum adsorption
      capacity (Q(0)=0.335 mg g(-1)) was used as an adsorbent in column studies. The
      optimized flow rate of 2.5 ml min(-1) and bed height 10 cm were used to determine
      the effect of metal ion concentration on removal of Cr(VI). Applying the BDST
      model to calculate the adsorption capacity (N(0)) of column, which showed 4.56 x
      10(-5), 7.28 x 10(-5), 6.89 x 10(-5), 3.07 x 10(-5), 2.80 x 10(-5)mg g(-1) for 4,
      8, 12, 16 and 20 mg dm(-3) of Cr(VI), respectively. Batch sorption proved to be
      more efficient than the column sorption and hence batch sorption was used to
      remove Cr(VI) from a textile dyeing industry wastewater. The phytotoxic effect of
      treated and untreated wastewater was studied against Zea mays. Toxicity was
      reduced by 50% in the treated effluent.

PMID- 15982703
TI  - Influence of plant growth promoting bacteria and Cr6+ on the growth of Indian
      mustard.
AB  - The Cr(6+) resistant plant growth promoting bacteria (PGPB), Pseudomonas sp. PsA4
      and Bacillus sp. Ba32 were isolated from heavy metal contaminated soils and their
      plant growth promoting activity on the Indian mustard (Brassica juncea) were
      assessed with different concentrations of Cr(6+) in soil. Production of
      siderophores and the solubilization of phosphate were observed in both strains,
      PsA4 and Ba32. Production of IAA was only observed in strain PsA4. Inoculation of
      PsA4 or Ba32 promoted the growth of plants at 95.3 and 198.3 microg of Cr(6+)g(
      1) soil. The maximum growth was observed in the plants inoculated with strain
      PsA4. Both strains, PsA4 and Ba32 did not influence the quantity of accumulation
      of chromium in root and shoot system. The present observations showed that the
      strains PsA4 and Ba32 protect the plants against the inhibitory effects of
      chromium, probably due to the production of IAA, siderophores and solubilization
      of phosphate.

PMID- 15982704
TI  - Indoor and outdoor bioaerosol levels at recreation facilities, elementary
      schools, and homes.
AB  - One major deficiency in linking environmental exposure to health effects is the
      current lack of data on environmental exposure. Therefore, to address this issue,
      the present study measured the bacterial and fungal concentrations in the indoor
      and outdoor air from two types of recreation facility (42 bars and 41 Internet
      cafes), 44 classrooms at 11 elementary schools, and 20 homes under uncontrolled
      environmental conditions during both summer and winter. No major environmental
      problems were reported at the four microenvironments being investigated during
      the entire study period. Bacteria and fungi were found in all the air samples,
      and the environmental occurrence of individual fungi was in the order of
      Cladosprium, Penicillium, Aspergillus, and Alternaria. The six parameters
      surveyed in the present study were all found to influence the indoor and outdoor
      bioaerosol levels: microenvironment type, sampling time in elementary school
      classrooms, agar type for measuring the fungal species, seasonal variation,
      facility location, and summer survey periods. The indoor and outdoor air
      concentrations of bacteria and fungi found in this study were comparable to those
      in other reports, with GM values for the total bacteria and total fungi between
      10 and 10(3) colony-forming units per cubic meter of air (CFU m(-3)). The fungal
      concentrations found at most of the indoor environments fell within the specified
      guidelines of the American Conference of Government Industrial Hygienists
      (ACGIH), between 100 and 1000 CFU m(-3) for the total fungi. However, the indoor
      bioaerosol concentrations at most of the surveyed environments exceeded the
      Korean indoor bioaerosol guideline (800 CFU m(-3)). Consequently, the current
      findings suggest the need for reducing strategy for indoor microorganisms at the
      surveyed microenvironments.

PMID- 15982705
TI  - Removal of polycyclic aromatic hydrocarbons from manufactured gas plant
      contaminated soils using sunflower oil: laboratory column experiments.
AB  - Laboratory column experiments were performed to remove PAHs (polycyclic aromatic
      hydrocarbons) from two contaminated soils using sunflower oil. Two liters of
      sunflower oil was added to the top of the columns (33 cm x 21 cm) packed with 1
      kg of PAH-contaminated soil. The sunflower oil was applied sequentially in two
      different ways, i.e. five additions of 400 ml or two additions of 1l. The
      influence of PAH concentration and the volume of sunflower oil on PAH removal
      were examined. A soil respiration experiment was carried out and organic carbon
      contents of the soils were measured to determine degradability of remaining
      sunflower oil in the soils. Results showed that the sunflower oil was effective
      in removing PAHs from the two soils, more PAHs were removed by adding sunflower
      oil in two steps than in five steps, probably because of the slower flow rate in
      the former method. More than 90% of total PAHs was removed from a heavily
      contaminated soil (with a total 13 PAH concentration of 4721 mg kg(-1)) using 4 l
      of sunflower oil. A similar removal efficiency was obtained for another
      contaminated soil (with a total 13 PAH concentration of 724 mg kg(-1)), while
      only 2l was needed to give a similar efficiency. Approximately 4-5% of the
      sunflower oil remained in the soils. Soil respiration curves showed that
      remaining sunflower oil was degraded by allowing air exchange and supplying with
      nutrients. Organic carbon content of the soil was restored to original level
      after 180 d incubation. These results indicated that the sunflower oil had a
      great capacity to remove PAHs from contaminated soils, and sunflower oil
      solubilization can be an alternative technique for remediation of PAH
      contaminated soils.

PMID- 15982706
TI  - Occurrence and accumulation of organochlorine contaminants in swordfish from
      Mediterranean Sea: a case study.
AB  - Polychlorinated biphenyls including coplanar congeners and DDT compounds were
      measured in the liver of a teleost species: namely, Xiphias gladius. PCB
      concentrations (median: 1121 ng/g lipid wt) were comparable with DDT levels
      (median: 1236 ng/g lipid wt). PCBs revealed a profile dominated by hexa-, penta-
      and heptachlorinated congeners. Among DDTs, the compound in the greatest
      concentration was p,p'-DDE, representing 70% of the total DDT burden, followed by
      o,p'-DDT>p,p'-DDT>p,p'-DDD=o,p'-DDD. Mean total 2,3,7,8-TCDD equivalent of five
      coplanar PCBs was 8.83 pg/g lipid weight. The isomers with higher TEQs values
      were non-ortho congeners than mono-ortho ones.

PMID- 15982707
TI  - Evaluation of biochemical effects related to perfluorooctane sulfonic acid
      exposure in organohalogen-contaminated great tit (Parus major) and blue tit
      (Parus caeruleus) nestlings.
AB  - A perfluorooctane sulfonic acid (PFOS) biomonitoring survey was conducted on
      great tit (Parus major) and blue tit (Parus caeruleus) nestlings from
      Blokkersdijk, a bird reserve in the proximity of a fluorochemical plant in
      Antwerp (Belgium) and Fort IV, a control area. PFOS, together with 11
      organochlorine pesticides, 20 polychlorinated biphenyl congeners and 7
      polybrominated diphenyl ethers were measured in liver tissue. The hepatic PFOS
      concentrations at Blokkersdijk (86-2788 and 317-3322 ng/g wet weight (ww) for
      great and blue tit, respectively) were among the highest ever measured and were
      significantly higher than at the control area (17-206 and 69-514 ng/g ww for
      great and blue tit, respectively). The hepatic PFOS concentration was species-
      and sex-independent and correlated significantly and positively with the serum
      alanine aminotransferase activity and negatively with the serum cholesterol and
      triglyceride levels in both species but did not correlate with condition or serum
      protein concentration. In the great tit, a significant positive correlation was
      observed between the liver PFOS concentration and the relative liver weight. In
      the blue tit, the hepatic PFOS concentration correlated positively and
      significantly with hematocrite values. None of the investigated organohalogen
      pollutants except for PFOS were suggested to be involved in the observed
      biological alterations.

PMID- 15982708
TI  - Elemental characterization of PM10, PM2.5 and PM1 in the town of Genoa (Italy).
AB  - The particulate matter (PM) concentration and composition, the PM10, PM2.5, PM1
      fractions, were studied in the urban area of Genoa, a coastal town in the
      northwest of Italy. Two instruments, the continuous monitor TEOM and the
      sequential sampler PARTISOL, were operated almost continuously on the same site
      from July 2001 to September 2004. Samples collected by PARTISOL were weighted to
      obtain PM concentration and then analysed by PIXE (particle induced X-ray
      emission) and by ED-XRF (energy dispersion X-ray fluorescence), obtaining
      concentrations for elements from Na to Pb. Some of the filters used in the TEOM
      microbalance were analysed by ED-XRF to calculate Pb concentration values
      averaged over 7-30 d periods.

PMID- 15982709
TI  - Toxicity of uranium and copper individually, and in combination, to a tropical
      freshwater macrophyte (Lemna aequinoctialis).
AB  - Copper (Cu) and uranium (U) are of potential ecotoxicological concern to tropical
      freshwater biota in northern Australia, as a result of mining activities. Few
      data are available on the toxicity of U, and no data are available on the toxic
      interaction of Cu and U, to freshwater biota. This study determined the toxicity
      of Cu and U individually, and in combination, to a tropical freshwater
      macrophyte, Lemna aequinoctialis (duckweed), in a synthetic soft water (27
      degrees C; pH, 6.5; hardness, 40 mg CaCO3 l-1, alkalinity, 16 mg CaCO3 l-1),
      typical of many fresh surface waters in coastal northern Australia. The growth
      rate of L. aequinoctialis decreased with increasing Cu or U concentrations, with
      the concentration of Cu inhibiting growth by 50% (EC50) being 16+/-1.0 microg l
      1, with a minimum detectable effect concentration (MDEC) of 3.2 microg l-1. The
      concentration of U inhibiting growth by 50% (EC50) was 758+/-35 microg l-1 with a
      MDEC of 112 microg l-1. The EC50 value for the exposure of L. aequinoctialis to
      equitoxic mixtures of Cu and U was significantly (P0.05) higher than one toxic
      unit (1.35; 95% confidence interval, 1.18-1.52), indicating that the combined
      effects of Cu and U are less than additive (antagonistic). Therefore, inhibition
      of the growth rate of L. aequinoctialis was reduced when Cu and U were present in
      equitoxic mixtures, relative to individual metal exposures. Since non-additive
      (e.g. antagonistic) interactions of metal mixtures cannot be predicted using
      current mixture models, these results have important potential implications for
      the protection of freshwater ecosystems through the derivation of national water
      quality guidelines.

PMID- 15982710
TI  - The use of a sequential leaching procedure for heavy metal fractionation in green
      liquor dregs from a causticizing process at a pulp mill.
AB  - A five-stage sequential leaching procedure was used to fractionate heavy metals
      (Cd, Cu, Pb, Cr, Zn, Fe, Mn, Ni, Co, As, V, Ba and Ti) in green liquor dregs into
      the following fractions: (1) water-soluble fraction (H2O), (2) exchangeable
      fraction (CH3COOH), (3) easily reduced fraction (HONH3Cl), (4) oxidizable
      fraction (H2O2 + CH3COONH4), and (5) residual fraction (HF + HNO3 + HCl). The
      green liquor dregs were derived from a causticizing process at a pulp mill at
      Kemi, Northern Finland. According to the leaching studies, the leachability of
      heavy metals in the water-soluble fraction varied between 0.5 and 2 mg kg(-1)
      expressed on a dry weight (d.w.) basis, indicating relatively low bioavailability
      of the metals. However, the concentration of Mn (2065 mg kg(-1); d.w.) showed a
      strong and of Zn (17.6 mg kg(-1); d.w.), Ni (39.7 mg kg(-1); d.w.) and Ba (32.0
      mg kg(-1); d.w.) slightly tendency to be extracted in the exchangeable fraction.
      In addition, Zn, Mn, Ni, Co, V and Ba showed clear leachability in the easily
      reduced fraction, as well as Cd, Cu, Cr, Zn, Mn, As and Ba in the oxidizable
      fraction. For Cd, Cu, Cr, Zn, Mn, Ni, Co, Ba and Ti, the sum of leachable heavy
      metal concentrations in fractions 1-5 agreed relatively well with the "total"
      heavy metal concentrations. Recoveries of the sum of fractions 1-5 were 84-56% of
      those obtained by the US EPA method 3052 (i.e. concentrations obtained after
      microwave oven digestion with a mixture of HF and HNO3).

PMID- 15982711
TI  - Particle size distributions of polycyclic aromatic hydrocarbons in rural and
      urban atmosphere of Tianjin, China.
AB  - The size distributions of 16 polycyclic aromatic hydrocarbons (PAHs) and particle
      mass less than 10 microm in aerodynamic diameter (Dp) were measured using a nine
      stage low-volume cascade impactor at rural and urban sites in Tianjin, China in
      the winter of 2003-2004. The particles exhibited the trimodal distribution with
      the major peaks occurring at 0.43-2.1 and 9.0-10.0 microm for both urban and
      rural sites. The concentrations of the total PAH (sum of 16 PAH compound) at
      rural site were generally less than those of urban site. Mean fraction of 76.5%
      and 63.9% of the total PAH were associated with particles of 0.43-2.1 microm at
      rural and urban sites, respectively. Precipitation, temperature, wind speed and
      direction were the important meteorological factors influencing the concentration
      of PAHs in rural and urban sites. The distributions of PAHs concentration with
      respect to particle size were similar for rural and urban samples. The PAHs
      concentrations at the height of 40 m were higher than both of 20 and 60 m at
      urban site, but the mass median diameter (MMD) of total PAH increased with the
      increasing height. The mid-high molecular weight (278 >or= MW >or= 202) PAHs were
      mainly associated with fine particles (Dp <or= 2.1 microm), whereas low molecular
      weight (128 >or=MW >or=178) PAHs were distributed in both of fine and coarse
      particle. The fraction of PAHs associated with coarse particles (Dp>2.1 microm)
      decreased with increasing molecular weight. The relatively consistent
      distribution of PAHs seemed to indicate the similar combustion source of PAHs at
      both of rural and urban sites. The fine differences of concentration and
      distribution of PAHs at different levels at urban site suggested that the
      different source and transportation path of particulate PAHs.

PMID- 15982712
TI  - Nonequilibrium sorption of phenols onto geosorbents: the impact of pH on
      intraparticle mass transfer.
AB  - While the pH effect on sorption equilibrium of weak acids on natural sorbents was
      investigated in a number of studies, less is known about the pH dependence of
      sorption kinetics. This paper investigates the impact of pH on sorption kinetics
      during the transport of some selected phenols through a sandy aquifer material.
      Breakthrough curves measured in column experiments were analyzed using a mass
      transfer based nonequilibrium model designated as dispersed flow, film and
      particle diffusion model (DF-FPDM). In this model, the rate limiting
      intraparticle diffusion is characterized by the mass transfer coefficient, kSaV,
      which can be determined from breakthrough curves by curve fitting. The
      experimental results indicate that the kSaV is pH-dependent and inversely
      correlated with the pH-dependent distribution coefficient, K(d,app). Regression
      equations are presented that may be used to estimate approximate values of
      intraparticle mass transfer coefficients on the basis of experimentally
      determined or LFER predicted distribution coefficients.

PMID- 15982713
TI  - Modelling PAHs adsorption and sequestration in freshwater and marine sediments.
AB  - Chemical sequestration is a natural process taking place in sediments and soils
      which reduces the availability of hydrophobic compounds such as polycyclic
      aromatic hydrocarbons (PAHs). The rate of sequestration following the release of
      PAHs into the aquatic environment is still unexplored. To measure kinetic
      parameters and investigate governing factors of adsorption and sequestration of
      individual PAHs, natural sediment slurries were spiked with [2H]-PAHs and
      periodically extracted with a high molecular weight surfactant solution to
      determine changes in the available fraction over periods of 7-28 days. Dissolved
      and/or colloidal [2H]-PAHs were first adsorbed on particles within 4-7 days.
      Adsorbed molecules became slowly sequestered into sediment particles and were
      gradually more difficult to extract over a period of 17-20 days. An empirical
      model based on a three-compartment dynamic system was developed to quantify the
      sequestration rate constants of a group of seven selected PAHs. The sequestration
      process was assumed to be a first-order consecutive and irreversible two-stage
      reaction. The model was tested with lowly contaminated marine sediment and
      moderately contaminated freshwater sediment. Adsorption rate constants ranged
      between 0.056 h(-1) and 0.017 h(-1) and were approximately ten times higher than
      sequestration rate constants. Light PAHs were faster to enter into the
      sequestration process whereas colloidal dispersion of heavier less soluble PAHs
      reduced their adsorption rates. Although quite simple, this model was efficient
      to compute kinetic parameters for most PAHs studied and predict that only a small
      proportion of adsorbed PAHs would remain extractable after one month.

PMID- 15982714
TI  - The regeneration and recycle of chromium etching solutions using concentrator
      cell membrane technology.
AB  - The regeneration of chromium (VI) and the recovery of etched copper from chromium
      etching solutions by electrodialysis is improved by the addition of a
      concentrator cell in the catholyte chamber. The concentrator media used are ion
      exchange resins or activated carbon cloth. The maximum percentages for the
      regeneration of chromium and recovery of copper in these systems is however less
      than 80% and 90% respectively because of the competition between the processes of
      oxidation of Cr(III) and electrodeposition of copper. A novel combination of
      electrolysis with electrodialysis and concentrator cell technology is developed
      that achieves 92% chromium regeneration and 90% copper recovery.

PMID- 15982715
TI  - Desorption kinetics studies on PAH-contaminated soil under varying temperatures.
AB  - The purpose of this study was to investigate the effect of temperature on the
      release of polycyclic aromatic hydrocarbons (PAHs) from aged contaminated soil.
      The release of fluorene, phenanthrene, anthracene, fluoranthene and pyrene at 7,
      15, 18 and 23 degrees C was studied using a column leaching method with a
      hydraulic retention time of 0.5 h. As the temperature declined from 23 to 7
      degrees C the concentrations decreased by a factor of 11-12 for all the studied
      compounds except for anthracene, which only decreased by a factor 7. Rate
      constants at maximum release rate at the four studied temperatures were assessed.
      From temperature dependence studies, apparent activation energies of desorption,
      E*(des), were calculated. E*(des)-values appeared to be in the range of 105-137
      kJ mol(-1) for the studied PAHs and increased with the LeBas molar volume of the
      compounds. The increase of E*(des) with increased molecular size indicates
      stronger sorption with increased hydrophobicity of the compounds.

PMID- 15982716
TI  - Removal of SO2 from O2-containing flue gas by activated carbon fiber (ACF)
      impregnated with NH3.
AB  - Adsorption of SO(2) from the O(2)-containing flue gas by granular activated
      carbons (GACs) and activated carbon fibers (ACFs) impregnated with NH(3) was
      studied in this technical note. Experimental results showed that the ACFs were
      high-quality adsorbents due to their unique textural properties. In the presence
      of moisture, the desulphurization efficiency for the ACFs was improved
      significantly due to the formation of sulfuric acid. After NH(3) impregnation of
      ACF samples, nitrogen-containing functional groups (pyridyl C(5)H(4)N- and
      pyrrolyl C(4)H(4)N-) were detected on the sample surface by using an X-ray
      photoelectron spectrometer. These functional groups accounted for the enhanced
      SO(2) adsorption via chemisorption and/or catalytic oxidization.

PMID- 15982717
TI  - Screening 31 endocrine-disrupting pesticides in water and surface sediment
      samples from Beijing Guanting reservoir.
AB  - For screening 31 potential or suspected endocrine-disrupting pesticides in water
      and surface sediments, a multiresidue analysis method based on gas chromatography
      with electron capture detection (GC/ECD) was developed. Solid phase extraction
      (SPE) technology with Oasis HLB cartridge was also applied in sample extraction.
      The relevant mean recoveries were 70-103% and 71-103% for water and sediment,
      respectively. Relative standard deviations (RSD) are 2.0-7.0%, 4.0-8.0% for water
      and sediment, respectively. Thirty one pesticides (alpha-HCH, beta-HCH, gamma
      HCH, delta-HCH, hexachlorobenzene (HCB), aldrin, heptachlor, endosulfan I & II,
      p,p'-DDD, o,p'-DDT, p,p'-DDT, p,p'-DDE, endrin aldehyde, endosulfan sulphate,
      methoxychlor, hepachlor epoxide, alpha-chlordane, gamma-chlordane, dieldrin,
      endrin, dicofol, acetochlor, alachlor, metolachlor, chlorpyriphos, nitrofen,
      trifluralin, cypermethrin, fenvalerate, deltamethrin) in water and surface
      sediment samples from Beijing Guanting reservoir were analyzed. Concentrations of
      pesticides ranged from 7.59 to 36.0 ng g(-1) on a dry wt. basis for sediment
      samples, from 279.3 to 2740 ng l(-1) for pore waters and from 48.8 to 890 ng l(
      1) for water samples, respectively, with a mean concentration of 10.7 ng g(-1) in
      sediment, 735 ng l(-1) in pore water and 295 ng l(-1) in water, respectively. The
      data obtained provides information on the levels and sources of endocrine
      disrupting pesticides in Guanting reservoir. These results underscore the need to
      improved environmental protection measures in order to reduce the exposure of the
      population and aquatic biota to these endocrine-disrupting compounds.

PMID- 15982718
TI  - Study on the fluorescence characteristics of bromadiolone in aqueous and
      organized media and application in analysis.
AB  - The fluorescence spectroscopic behavior of bromadiolone (anticoagulant
      rodenticide), a substituted 4-hydroxycoumarin derivative, was investigated in
      water and in organized media like micelles and cyclodextrins. A detailed study on
      various photophysical parameters like fluorescence intensity (I(F)), quantum
      yield (phi), lifetime (tau) and steady state fluorescence anisotropy (r) of
      bromadiolone in aqueous and in organized media was carried out. Bromadiolone in
      aqueous solution was observed to be in an aggregated state, thereby showing weak
      emission due to self-quenching. Marked enhancement of fluorescence intensity was
      observed in organized media like micelles and beta-cyclodextrin. A preliminary
      investigation has been done to find out whether this enhancement of fluorescence
      can be used to develop a sensitive analytical method for determination of
      bromadialone in aqueous media. A linear relationship between the fluorescence
      intensity and concentration of bromadiolone was observed in the range of 0.15-7.9
      microg ml(-1) in cetyltrimethylammonium bromide (CTAB) and 0.5-26.4 microg ml(-1)
      in beta-cyclodextrin medium. The lower detection limit was found to be 37 ng ml(
      1) in presence of CTAB and 23 ng ml(-1) in beta-cyclodextrin. Comparison with 4
      hydroxycoumarin, an unsubstituted analogue, was made.

PMID- 15982719
TI  - Cadmium phytotoxicity: Quantitative sensitivity relationships between classical
      endpoints and antioxidative enzyme biomarkers.
AB  - In this work, cadmium phytotoxicity and quantitative sensitivity relationships
      between different hierarchical endpoints in plants cultivated in a contaminated
      soil were studied. Thus, germination rate, biomass growth and antioxidative
      enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione
      reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L.
      cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests
      were carried out according to an International Standard Organization method and
      the results were analyzed by ANOVA followed by Williams' test. The concentration
      of Cd2+ that had the smallest observed significant negative effect (LOEC) on
      plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and
      Chinese cabbage, respectively. Activity of all enzymes studied increased
      significantly compared to enzyme activity in plant controls. For lettuce, LOEC
      values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione
      reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged
      from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for
      catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil)
      ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39
      (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical
      (i.e. enzyme activity) endpoints were compared to establish a sensitivity
      ranking, which was: enzyme activity>biomass>germination rate. For cadmium-soil
      contamination, the determination of quantitative sensitivity relationships (QSR)
      between classical and antioxidative enzyme biomarkers showed that the most
      sensitive plant species have, generally, the lowest QSR values.

PMID- 15982720
TI  - Laser ablation ICP-MS analysis of the radial distribution of lead in the femur of
      Alligator mississippiensis.
AB  - A laser ablation ICP-MS technique has been used to examine the radial
      distribution of lead in transverse sections of alligator femur. Annual bone
      growth in the femur results in the deposition of incremental layers of calcified
      tissue at the periphery of existing bone. Patterns of lead concentration within
      these layers provide a record of time-dependent accumulation from which exposure
      history can potentially be deduced. Femur specimens obtained from captive-reared
      alligators exhibited levels of lead accumulation that were entirely consistent
      with previously documented clinical signs of lead intoxication. In contrast,
      femurs obtained from wild alligators contained only minor amounts of lead that
      were likely accumulated as a result of incidental exposure.

PMID- 15982721
TI  - Dilemmas in herbal medicine: the clinician's viewpoint.

PMID- 15982722
TI  - Modelling of calcium handling in airway myocytes.
AB  - Airway myocytes are the primary effectors of airway reactivity which modulates
      airway resistance and hence ventilation. Stimulation of airway myocytes results
      in an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and the
      subsequent activation of the contractile apparatus. Many contractile agonists,
      including acetylcholine, induce [Ca(2+)](i) increase via Ca(2+) release from the
      sarcoplasmic reticulum through InsP(3) receptors. Several models have been
      developed to explain the characteristics of InsP(3)-induced [Ca(2+)](i)
      responses, in particular Ca(2+) oscillations. The article reviews the modelling
      of the major structures implicated in intracellular Ca(2+) handling, i.e.,
      InsP(3) receptors, SERCAs, mitochondria and Ca(2+)-binding cytosolic proteins. We
      developed theoretical models specifically dedicated to the airway myocyte which
      include the major mechanisms responsible for intracellular Ca(2+) handling
      identified in these cells. These biocomputations pointed out the importance of
      the relative proportion of InsP(3) receptor isoforms and the respective role of
      the different mechanisms responsible for cytosolic Ca(2+) clearance in the
      pattern of [Ca(2+)](i) variations. We have developed a theoretical model of
      membrane conductances that predicts the variations in membrane potential and
      extracellular Ca(2+) influx. Stimulation of this model by simulated increase in
      [Ca(2+)](i) predicts membrane depolarisation, but not great enough to trigger a
      significant opening of voltage-dependant Ca(2+) channels. This may explain why
      airway contraction induced by cholinergic stimulation does not greatly depend on
      extracellular calcium. The development of such models of airway myocytes is
      important for the understanding of the cellular mechanisms of airway reactivity
      and their possible modulation by pharmacological agents.

PMID- 15982723
TI  - Clinical implication of laparoscopic pelvic lymphadenectomy in patients with
      vulvar cancer and positive groin nodes.
AB  - OBJECTIVE: At present, no clear guidelines for the treatment of patients with
      vulvar cancer and positive groin nodes exist. In general, the decision for
      additional pelvic radiation is based on findings by imaging techniques and/or the
      number of groin nodes involved. The aim of this case series was to demonstrate
      that histologic result of laparoscopic removed pelvic lymph nodes can be used to
      select patients who should not undergo pelvic irradiation. METHODS: From July
      1997 to October 2004, 12 consecutive patients with primary or recurrent vulvar
      cancer underwent laparoscopic pelvic lymphadenectomy following primary or
      secondary surgical treatment. RESULTS: There were 8 patients with primary cancer
      of the vulva and 4 patients with recurrent disease in the inguinal and/or pelvic
      lymph nodes. The mean age was 61 (26-83) years and the mean body-mass-index was
      27.1 (20.8-36.6). Positive groin nodes were found in five patients on the right
      side and in five patients on the left side; in one patient, positive groin nodes
      were present in both sides. In another patient with a history of vulvar cancer
      and positive groin nodes the CT-scan indicated the presence of positive iliac and
      paraaortic lymph nodes. Only in two patients tumor involved lymph nodes were
      diagnosed by laparoscopic pelvic lymphadenectomy (one left-sided, one right
      sided). The number of harvested pelvic lymph nodes was 13.7 (5-20) in unilateral
      and 27.8 (16-37) in bilateral lymphadenectomy. The histologic examination of
      removed pelvic lymph nodes confirmed pelvic radiation in only 2 out of 12
      patients, whereas 10 patients were spared from whole pelvis irradiation.
      CONCLUSION: With respect to small sample size, laparoscopic lymphadenectomy seems
      to be a good tool to avoid unnecessary pelvic radiation in patients with vulvar
      cancer and confirmed positive groin nodes.

PMID- 15982724
TI  - Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in
      stages I and II endometrial cancer. Operating data, follow up and survival.
AB  - OBJECTIVE: To assess the feasibility of laparoscopy in the treatment of early
      stage endometrial carcinoma and follow up outcomes compared to classic
      laparotomy. METHODS: A retrospective review of 90 consecutive patients with
      endometrial cancer managed between January 1997 and December 2003. Two groups
      were defined whether they had been treated by laparoscopy (N = 38; LPS group) or
      by laparotomy (N = 37; LPM group). Nine patients treated by vaginal hysterectomy
      and 6 cases with stages III-IV were excluded from the study. RESULTS: Both groups
      were comparable in mean age and mean BMI. Mean operating time was longer for LPS
      group, 164.91 +/- 5.60 (77-240) vs. 129.97 +/- 5.08 (60-180) min (P < 0.05).
      Intraoperative complications were seen in 7 patients (18.9%) from LPM and in 5
      cases (13.2%) in the laparoscopic group. Two patients (5.2%) initially evaluated
      by laparoscopy were converted into laparotomy due to an increasing and
      uncontrollable hypercapnia. There were more post-operative complications in
      patients managed by laparotomy (14 cases; 38.8%), than by laparoscopy (7 cases;
      18.4%) (P < 0.05). Blood transfusion was necessary in 4 patients (10.8%) in LPM
      group while none was required in LPS group (P < 0.01). Hospital readmission was
      only recorded in 3 patients treated by laparotomy (6.7%) (P < 0.05). Hospital
      stay was longer in LPM group 7.06 +/- 0.58 (4-21) vs. LPS 5.04 +/- 0.73 (2-17)
      days (P < 0.05). With a median follow up of 53.21 +/- 4.32 months for LPM (5-90)
      and 36.31 +/- 2.75 months for LPS (9-65) there was no significant difference in
      disease recurrence between the two groups. CONCLUSION: Laparoscopic staging
      combined with vaginal hysterectomy appears to be a feasible alternative to
      classical surgical approach in patients with early stage I or II endometrial
      carcinoma.

PMID- 15982725
TI  - The role of cytoreductive surgery in nongenital cancers metastatic to the
      ovaries.
AB  - OBJECTIVE: To investigate the role of cytoreductive surgery in patients with
      nongenital cancers metastatic to the ovaries. PATIENTS AND METHODS: One hundred
      and fifty-four patients with nongenital cancers metastatic to the ovaries treated
      in Hacettepe University Hospital, Gynecologic Oncology Unit between 1982 and 2004
      years were retrospectively evaluated. Data were obtained from patients' records
      and pathology reports. Demographic characteristics, prognostic factors, 5-year
      and median survivals were analyzed in all patients. RESULTS: During study period,
      nongenital cancers metastatic to the ovaries constituted 9% of all malignant
      ovarian neoplasms. Primary cancers were breast (35), stomach (35) and colorectal
      (33) cancers, lymphoma (17), undetermined origin (16), appendix (7), ileum (4),
      pancreas (3), gallbladder cancer (2) and mesothelioma (2). Of patients, 67% were
      premenopausal and 33% were postmenopausal. Although most common presenting
      symptoms were abdominal distension with dyspeptic complaints in 46%, abdominal
      mass in 22%, and pressure symptoms in 8.4%, 15 patients (10%) were asymptomatic
      and were diagnosed in routine control examinations. Total abdominal hysterectomy
      and bilateral salpingo-oophorectomy (TAH + BSO), omentectomy, and bilateral
      pelvic and para-aortic lymphadenectomy (BP-PALND) with cytoreduction were
      performed in 102 patients (66%), TAH + BSO + omentectomy in 21 patients (14%),
      TAH + BSO in 23 patients (15%), minimal surgical effort including BSO or biopsy
      in 8 patients (5%). Eighty-four percent of patients received adjuvant treatment
      according to the primary origins. Mean follow-up was 47.3 +/- 5.9 months.
      Overall, 5-year survival was 36% and median survival was 42 months. Comparison of
      median survival times for the primary sites showed a significant overall
      differences (P = 0.0001) and were as follows: breast 54 months, stomach 18
      months, colorectal 48 months, lymphoma 181 months, unknown primary 16 months,
      appendix 18 months, ileum 40 months, pancreas 3 months, gallbladder 8 months and
      mesothelioma 20 months. Median survival time of patients who underwent
      cytoreductive surgery was 48 months, compared with 26 months for patients with
      suboptimal cytoreductive surgery (P = 0.0039). The 5-year survival rate was 47%
      and 23%, respectively. Multivariate analysis identified age, menopausal status,
      primary site, diffuse peritoneal involvement and type of operation as prognostic
      factors. CONCLUSION: Presence of ovarian metastasis is associated with a poor
      prognosis in nongenital cancers. Surgery is essential for diagnosis of primary
      tumor and necessary for relief of symptoms. Cytoreductive surgery seems to have a
      beneficial effect on survival of selected patients, especially for patients with
      colorectal cancer metastatic to the ovary.

PMID- 15982726
TI  - Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for
      advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II),
      IGF binding protein 3 (IGF-BP3) and VEGF-A [corrected].
AB  - OBJECTIVES: An early non-invasive diagnosis of cervical cancer and its metastasis
      can save lives. We have shown that serum IGF-II levels can be effectively used
      for a specific early diagnosis of cervical cancer. Here, we shall determine if
      serum levels of vascular endothelial growth factors B and C (VEGF-A [corrected]
      VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for
      an early diagnosis of advanced metastatic cervical cancer and compare these
      levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3).
      MATERIAL AND METHODS: (a) Serum levels of IGF-II, IGF-BP3, VEGF-A [corrected]
      (VEGF(165)) and VEGF-C (ELISA kits) were determined in: 82 controls with normal
      Pap smears; 29 women with atypical squamous cells of undetermined significance
      (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial
      neoplasia (CIN) on biopsy; 8 pre-therapy CIN-I; 23 successfully treated CIN-I; 75
      persistent CIN-I; 14 CIN-II/III pre-therapy; 14 successfully treated CIN-II/III;
      70 persistent CIN-II/III; 86 pre-therapy cervical cancer; 26 in early grades of
      cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer
      patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and
      57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5
      women with progressing cervical cancer were also tested. (c) Serum and tissue
      VEGF-C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative
      immunofluorescent antibody assay) samples from controls, early cervical cancer,
      late cervical cancer, ovarian cancer and endometrial cancer patients. Student's t
      test, chi-square analysis and linear regression analysis were used. RESULTS: (a)
      As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on
      biopsy and continued to be elevated in CIN (all grades; pre-therapy and
      persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum
      IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN
      I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers
      (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF-BP3 showed a
      significant decrease with advancing disease. Serum VEGF-A [corrected] levels were
      the highest in pre-therapy, early, advanced and persistent cervical cancer, as
      well as in ovarian and endometrial cancers. Serum VEGF-C levels, on the other
      hand, were the highest in late and persistent cervical cancers, but not in
      ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum
      levels of the growth factors showed similar trends. (c) VEGF-C levels in serum
      and tissue were elevated in cervical cancers especially in advanced grades, while
      they were normal in serum and tissue from the controls and women with ovarian and
      endometrial cancers. There was a highly significant positive correlation between
      VEGF-C and IGF-II and a negative correlation between IGF-BP3 and VEGF-C (P <
      0.0001). CONCLUSION: Serum IGF-II up-regulation is specific to cervical cancer
      and helps in the early diagnosis of malignant proliferation, while serum VEGF-C
      up-regulation appears to be a unique marker for an early diagnosis of cervical
      cancer metastasis. VEGF-C and IGF-II systems appear to be interrelated in
      cervical cancer, contributing to the early malignant cell proliferation and
      lympho-vascular metastasis. Serum IGF-BP3 and VEGF-A [corrected] appear to be
      common markers for all gynecological cancers.

PMID- 15982727
TI  - Rewarding properties of the stereoisomers of 4-methylaminorex: involvement of the
      dopamine system.
AB  - 4-Methylaminorex is a potential psychostimulant drug of abuse that exists as four
      stereoisomers: cis-4R,5S, cis-4S,5R, trans-4S,5S, and trans-4R,5R. The racemic
      mixture of the cis-isomers has been encountered in illicit samples, but previous
      animal studies suggest that also the trans-isomers could have similar stimulant
      like properties. We tested whether the stereoisomers possess rewarding properties
      and compared their potency using the conditioned place preference method in rats.
      Furthermore, the involvement of the brain dopaminergic system in the 4
      methylaminorex reward was tested with the dopamine D1- and D2-receptor
      antagonists SCH 23390 and raclopride administered systemically, or with the
      neurotoxin 6-hydroxydopamine injected into the nucleus accumbens. All the four
      isomers induced place preference, with no apparent differences in their potency.
      SCH 23990 and raclopride attenuated 4-methylaminorex-induced increase in place
      preference, and 6-hydroxydopamine also tended to be efficacious. These findings
      indicate that all the four stereoisomers of 4-methylaminorex possess rewarding
      properties and thus abuse potential; the trans-isomers are at least as potent as
      the cis-isomers. Furthermore, the brain dopaminergic system appears to be
      involved in the 4-methylaminorex-reward.

PMID- 15982728
TI  - Effects of interleukin-1 and endotoxin in the forced swim and tail suspension
      tests in mice.
AB  - Male CD-1 mice were administered interleukin-1beta (IL-1beta) and bacterial
      endotoxin (lipopolysaccharide, LPS) and subsequently tested in the tail
      suspension test (TST), the Porsolt forced swim test (FST), and in the open field.
      IL-1beta (100, 300 and 1000 ng/mouse) injected intraperitoneally (i.p.) 90 min
      before the test induced a dose-dependent increase in the time spent immobile in
      the TST and the time spent floating in the FST. These responses were
      statistically significant only at the higher doses of IL-1beta (300 and 1000 ng).
      Nevertheless, all three doses of IL-1beta significantly decreased line crossings
      and rears in the open field and depressed food intake and body weight. Very
      similar effects were induced by LPS. Doses of 1 and 5 mug i.p. increased
      immobility time in the TST and floating time in the FST, but the same doses
      strongly depressed locomotor activity and body weight. These results indicate
      that both IL-1beta and LPS can induce depression-like effects in the TST and the
      FST. However, the doses necessary to induce these changes reduced feeding and
      activity in an open field, so that the effects observed in the FST and TST could
      be attributed to a general reduction in locomotor activity. Thus the results
      obtained in these two animal tests commonly used to test antidepressant
      properties do not provide strong support for an IL-1 hypothesis of depression.

PMID- 15982729
TI  - Pharmacological evidence for the activation of Ca2+-activated K+ channels by
      meloxicam in the formalin test.
AB  - The possible participation of K+ channels in the antinociceptive action of
      meloxicam was assessed in the 1% formalin test. Local peripheral administration
      of meloxicam produced a dose-dependent antinociception only during the second
      phase of the formalin test. K+ channel blockers alone did not modify formalin
      induced nociceptive behavior. However, local peripheral pretreatment of the paw
      with charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+
      channel inhibitors, respectively), 4-aminopyridine and tetraethylammonium (non
      selective voltage-dependent K+ channel inhibitors), but not glibenclamide or
      tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented
      meloxicam-induced antinociception. It is concluded that meloxicam could open
      large- and small-conductance Ca2+-activated K+ channels, but not ATP-sensitive K+
      channels, in order to produce its peripheral antinociceptive effect in the
      formalin test. The participation of voltage-dependent K+ channels was also
      suggested, but since non-selective inhibitors were used the data await further
      confirmation.

PMID- 15982730
TI  - Successful piglet production by IVF of oocytes matured in vitro using NCSU-37
      supplemented with fetal bovine serum.
AB  - Recently, piglets have been obtained from in vitro-produced blastocysts by using
      in vitro maturation systems in which oocytes have been matured in North Carolina
      State University (NCSU) solution supplemented with porcine follicular fluid
      (PFF). However, PFF is not available commercially. To prepare PFF from the
      ovaries required time and effort and there is substantial variation in quality
      among batches. Furthermore, PFF is considered a potential source of infectious
      agents. We evaluated another commercially available potential protein source,
      fetal bovine serum (FBS), for in vitro maturation, to produce embryos and
      piglets. Cumulus-oocyte complexes were matured in NCSU-37 with PFF or with one of
      four batches of FBS. The proportions of oocytes with expanded cumulus cells were
      lower in all FBS batch groups (P < 0.05, 15-41%) than that in the PFF group
      (74%). The proportions of oocytes that matured were also lower in all FBS batch
      groups (P < 0.05, 26-41%) than in the PFF group (73%), irrespective of cumulus
      expansion. However, the proportions of oocytes that underwent germinal vesicle
      breakdown were almost the same in all groups (76-96%). After in vitro
      fertilization, the rate of sperm penetration into matured oocytes was higher in
      the PFF group (P < 0.05, 63%) than in one batch of FBS (22%) and removal of the
      compacted cumulus cells after maturation did not affect fertilization status
      (21%). Subsequent in vitro embryo culture of the PFF and FBS groups for 6 day
      resulted in similar rates of blastocyst formation (17 and 19%, respectively) and
      similar numbers of cells per blastocyst (43 and 46 cells, respectively). When
      blastocysts obtained from oocytes matured with FBS were transferred into two
      recipients, one became pregnant and farrowed seven piglets. Transfer of
      blastocysts obtained from oocytes matured with PFF into two other recipients
      resulted in one pregnancy and production of four piglets. These data suggested
      that porcine in vitro maturation in NCSU-37 supplemented with FBS reduced the
      maturational ability of oocytes, but once oocytes have matured, they have the
      same ability to develop to term after in vitro fertilization and embryo transfer
      as those matured with PFF.

PMID- 15982731
TI  - Concerted action between Ca2+ and hyperosmolality initiates sperm motility in
      amphioxus Branchiostoma belcheri tsingtauense.
AB  - This study investigated the effects of different environmental conditions on the
      initiation and maintenance of sperm motility in amphioxus Branchiostoma belcheri
      tsingtauense. The findings were that: (1) hyperosmolality in the absence of
      Ca(2+) ions did not initiate amphioxus sperm motility; (2) addition of Ca(2+)
      into EGTA-containing Ca(2+)-free artificial sea water (ASW), in which no sperm
      were motile, restored sperm motility; (3) Ca(2+) failed to induce sperm motility
      under conditions of hypoosmolality; (4) K(+) channel blockers quinine and 4
      aminopiridine did not suppress the initiation of sperm motility; and (5) changes
      in pH did not cause sperm motility in a solution isotonic to seawater without
      Ca(2+). In conclusion, we inferred that a concerted action between Ca(2+) and
      hyperosmolality was essential to initiate motility of amphioxus sperm, whereas
      K(+) and pH were indispensable to maintain motility.

PMID- 15982732
TI  - Non-Hodgkin's lymphoma after kidney transplantation: a single institution study.
AB  - We treated at our institution six patients with kidney transplantation and
      lymphoma. After the end of chemotherapy, re-introduction of therapeutic immune
      suppression was not necessary since, with a significant follow-up (median follow
      up of 26 months, range 12-36), no patient had severe renal function
      deterioration. These preliminary data suggest that, after lymphoma treatment,
      immune suppression can be withhold at least for 2 years. Restoration of a
      functional immune system may contribute to decrease the rate of lymphoma
      recurrence, in line with the absence of lymphoma relapse in our six patients, who
      are all still alive and in complete remission.

PMID- 15982733
TI  - Inhibition of NF-kappaB activity by BAY 11-7082 increases apoptosis in multidrug
      resistant leukemic T-cell lines.
AB  - Multidrug resistance (MDR) is the main reason for failure of cancer therapy with
      resistance to apoptosis being one of the mechanisms involved. Constitutive NF
      kappaB activity has been detected in many tumors contributing to oncogenesis and
      tumor survival whereas inhibition of NF-kappaB activity has proved to enhance
      cell death induced by chemotherapeutic agents. Consequently, the use of BAY 11
      7082, an irreversible inhibitor of IkappaB-alpha phosphorylation, could be
      beneficial in the treatment of certain tumors. Although there are several reports
      which demonstrate a transient activation of NF-kappaB by cytotoxic drugs, little
      is known about the role of NF-kappaB activation in the development of a
      chemoresistant phenotype in leukemic cells. In this study, we analyzed the
      relationship between NF-kappaB and the survival of murine leukemic drug resistant
      cell lines. The modulation of this transcription factor by BAY 11-7082 and the
      chemotherapeutic agents vincristine and doxorubicin was evaluated. The effect of
      BAY 11-7082 on the expression of genes containing NF-kappaB-binding sites was
      also studied. We found that the cell lines LBR-V160 and LBR-D160 (resistant to
      vincristine and doxorubicin, respectively) presented higher constitutive NF
      kappaB activity than the sensitive LBR- and the active complex contained both p50
      and p65 subunits. BAY 11-7082 (3.5 microM) inhibited constitutive NF-kappaB
      activity in the three cell lines whereas the anticancer agents did not. Treatment
      with BAY 11-7082 induced a higher percentage of apoptosis in LBR-V160 and LBR
      D160 than in LBR-. Cells treated with BAY 11-7082 displayed modulation of NF
      kappaB-inducible genes such as IL-10, IL-15, TNF-alpha and TGF-beta. Taken
      together, these data suggest that suppression of constitutive NF-kappaB activity
      by BAY 11-7082 may be a useful treatment for MDR leukemias.

PMID- 15982734
TI  - Anti-angiogenesis effects of meisoindigo on chronic myelogenous leukemia in
      vitro.
AB  - Meisoindigo, an active compound of a Chinese anti-leukemia medicine, has been
      effectively used in the treatment of chronic myelogenous leukemia (CML).
      Increasing evidences have demonstrated that angiogenesis is an important
      pathobiologic feature of CML. The anti-angiogenesis effect of meisoindigo on CML
      is unknown. In this study, we determined the effects of meisoindigo on the
      apoptosis, adherence and differentiation of endothelial cells as well as the
      secretion of vascular endothelial growth factor (VEGF) by CML cells. We found
      that VEGF level, measured by enzyme-linked immunosorbent assay (ELISA), was
      higher in bone marrow plasma from CML patients compared with the healthy controls
      (334.83+/-23.09 ng/L versus 102.36+/-38.76 ng/L, P<0.01). CML cell VEGF
      production was decreased after CML cells were treated with 10 micromol/L
      meisoindigo compared with the controls (212.10+/-46.13 ng/L versus 293.75+/-64.79
      ng/L, P<0.05). Ten micromole per liter of meisoindigo could induce time-dependent
      apoptosis of ECV304 cells determined by annexin-V. Treatment of ECV304 cells with
      meisoindigo for 48 h reduced the number of adherent cells and the expression of
      VCAM-1 compared with the control cells (43.78+/-9.09% versus 73.51+/-3.21%,
      P<0.05). Meisoindigo also inhibited tubule formation of HUVECs in an in vitro
      Matrigel after HUVECs were incubated with meisoindigo for 6 h. Our findings
      suggest that meisoindigo could inhibit angiogeneic process through decreasing the
      VEGF secretion in leukemic cells and also through inhibiting the proliferation,
      adhesion and differentiation of endothelial cells, causing the interruption of a
      reciprocal stimulatory loop between leukemic and endothelial cells. This effect
      may contribute to the anti-leukemic effect of this drug.

PMID- 15982735
TI  - NUP98-LEDGF fusion and t(9;11) in transformed chronic myeloid leukemia.
AB  - The molecular basis for disease progression in chronic myeloid leukaemia (CML) is
      poorly understood, but is believed to be a consequence of additional acquired
      genetic lesions. We describe here a case of CML who presented de novo in
      transformation with a t(9;11)(p21;p15) and NUP98-LEDGF fusion in addition to the
      t(9;22). The t(9;11) was present in only 2/45 (4%) of bone marrow metaphases, but
      17/20 (85%) of metaphases from peripheral blood, suggesting an extramedullary or
      focal origin. This is the first description of NUP98-LEDGF in CML and strengthens
      the association between disease progression in and NUP98 abnormalities.

PMID- 15982736
TI  - Molecular cloning and characterization of cecropin from the housefly (Musca
      domestica), and its expression in Escherichia coli.
AB  - A cDNA encoding housefly (Musca domestica) cecropin transcript was isolated from
      total RNA using RT-PCR, 3'RACE, and lambda gt11 cDNA library screening, and was
      expressed in Escherichia coli. This is the first report of a cecropin nucleotide
      and amino acid sequence in the housefly. The open reading frame of Md-Cec (189bp)
      encodes a precursor of 63 aa, which is comprised of a 23 aa signal peptide and a
      40 aa mature peptide. In terms of amino acid sequence, Md-Cec shares a high
      degree of identity (74-82%) with those of some Diptera insects. Northern blot, RT
      PCR and in situ hybridization analyses revealed that the prececropin was
      temporally expressed 5h after bacteria-challenge in larvae, and was induced in
      the fat body, epithelia of the body wall, and the epidermis of the midgut. The
      DNA fragment encoding mature Md-Cec was then subcloned into the pGEX-4T-1
      expression vector and was highly expressed in E. coli BL21 with IPTG induction.
      The expressed proteins, fused to glutathion S-transferase, were purified by
      glutathion-Sepharose 4B affinity chromatography and cleaved with thrombin,
      followed by gel filtration chromatography. Recombinant Md-Cec exhibited
      antimicrobial activity against E. coli.

PMID- 15982737
TI  - Atmospheric bulk deposition to the Lagoon of Venice Part II. Source apportionment
      analysis near the industrial zone of Porto Marghera, Italy.
AB  - Multivariate statistical analyses were applied to measurements of atmospheric
      deposition of total particulate (TSP), inorganic elements (Al, Ca, Na, K, Mg, Si,
      Mn, Fe, Zn, Ni, Cr, Cu, Pb, Cd, As, Hg, V and S) and organic compounds (PAH, PCB,
      HCB and PCDD/F) collected in four stations, all located in the Lagoon of Venice.
      Aerosols at the scale of the basin (i.e., within a distance of 20 km) were mainly
      characterised by two end-members, one natural (composed of mineral particulate
      and marine spray) and one anthropogenic (with at least two different source
      components), affecting the sites in various ways. Variability at the two distant
      (>20 km) sites (Valle Doga, Valle Figheri) was mainly due to natural components,
      whereas the other two stations (city of Venice, Dogaletto, approximately 5 km)
      were mainly impacted by industrial (and urban) sources. Total annual inputs were
      compared with the limits recently set by law (maximum allowed discharge=MAD). In
      the year of study, MAD values were exceeded for total As, Cd, Hg, Pb, dissolved
      Zn, PAH and PCDD/F. These results indicate that industrial sources gave rise to a
      quasi-permanent compositional (background) effect near the industrial area. The
      risk associated with atmospheric deposition should be quantified within the DSPIR
      framework to avoid future negative consequences in populations living in the
      vicinity of Porto Marghera.

PMID- 15982738
TI  - Yield and arsenate uptake of arbuscular mycorrhizal tomato colonized by Glomus
      mosseae BEG167 in As spiked soil under glasshouse conditions.
AB  - A glasshouse pot experiment was conducted to study the effect of arbuscular
      mycorrhizal (AM) colonization by Glomus mosseae BEG167 on the yield and arsenate
      uptake of tomato plants in soil experimentally contaminated with five As levels
      (0, 25, 50, 75 and 150 mg kg(-1)). Mycorrhizal colonization (50-70% of root
      length) was little affected by As application and declined only in soil amended
      with 150 mg As kg(-1). Mycorrhizal colonization increased plant biomass at As
      application rates of 25, 50 and 75 mg kg(-1). Shoot As concentration increased
      with increasing As addition up to 50 mg kg(-1) but decreased with mycorrhizal
      colonization at As addition rates of 75 and 150 mg kg(-1). Shoot As uptake
      increased with mycorrhizal colonization at most As addition levels studied, but
      tended to decrease with addition of 150 mg As kg(-1). Total P uptake by
      mycorrhizal plants was elevated at As rates of 25, 50 and 75 mg kg(-1), and more
      P was allocated to the roots of mycorrhizal plants. Mycorrhizal plants had higher
      shoot and root P/As ratios at higher As application rates than did non
      mycorrhizal controls. The soil of inoculated treatments had higher available As
      than uninoculated controls, and higher pH values at As addition levels of 25, 50
      and 75 mg kg(-1). Mycorrhizal colonization may have increased plant resistance to
      potential As toxicity at the highest level of As contamination studied.
      Mycorrhizal tomato plants may have potential for phytoextraction of As from
      moderately contaminated soils or phytostabilization of more highly polluted
      sites.

PMID- 15982739
TI  - Pollution historical trends as recorded by sediments at selected sites of the
      Venice Lagoon.
AB  - Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans
      (PCDFs) and hexaclorobenzene (HCB) were determined in three sediment cores of the
      Venice Lagoon: I1, from the San Giuliano Canal that is likely the main source of
      pollutants for the study area; E, representing the lagoon sediment of the zone of
      Campalto; and M3, typical of a salt marsh environment and mostly subject to
      atmospheric inputs. Maximum concentrations were found in core I1: 25-1858 ngI-TE
      kg(-1) (PCDD/Fs), 1.7-13 microg kg(-1) (HCB), and 107-717 microg kg(-1) (PCBs)
      are surficial and peak values, respectively. The lagoon sediment (E), is much
      less contaminated: 24-47 ngI-TE kg(-1) for PCDD/Fs, 2.3-3.6 microg kg(-1) for
      HCB, and 56-203 microg kg(-1) for PCBs, whereas M3 shows the lowest values: 1.6
      6.0 ngI-TE kg(-1) for PCDD/Fs, 0.3-0.6 microg kg(-1) for HCB, and 7.1-39 microg
      kg(-1) for PCBs. In any case, the recent trend is toward a decrease of pollutant
      concentration. The chronology of cores E and M3 is based on both 210Pb and 137Cs
      activity-depth profiles. The maximum concentrations of PCDD/Fs, HCB, and PCBs
      correspond to the years 1949, 1980, and 1968, respectively. The homologue
      profiles of PCDD/Fs confirm that I1 has been subject to an industrial source
      while the other sites also recorded significant contributions, changing over
      time, of octachlorinated dioxin from combustion. A comparison of the pollutant
      inventories, all normalised to 210Pb inventories, suggests that the atmospheric
      contribution to the contamination of the area of Campalto is low: the upper
      limits range from 6% (PCDD/Fs) to 17% (HCB).

PMID- 15982740
TI  - Contamination of persistent organic pollutants (POPs) and relevant management in
      China.
AB  - The status of typical persistent organic pollutant (POP) contamination in many
      media (e.g., farm produce, soil, human milk, water, and sediments) was surveyed
      and China's relevant countermeasures for controlling POPs were analyzed in this
      paper. The results showed that the proportion of organochlorine pesticides (OCPs)
      to all kinds of pesticides has descended significantly since 1983 when the OCPs
      were forbidden from being used. The spatial distribution characteristic of
      pesticide application in the whole country was as follows:
      southeast>central>northwest. The pesticide residues in food with high fat and
      high protein content were more than that in foodstuffs. The residual
      concentration in soil in the whole country was as follows: south>central>north.
      Furthermore, in vegetable fields, the residual concentration was higher than that
      in crop fields. As for human milk, the retained amount tended to decrease. In the
      recent two decades, although the reduction was 81.5%, it was still higher than
      that in some developed European and American countries. The rank of the residual
      concentrations of OCPs in different media was: human milk>animal
      foodstuff>soil>vegetable food>water and sediment. The initial relevant POP
      management in China can be traced back to 1982 when the Ordinance of Pesticide
      Management was enacted. Now, environmental control of POPs in China is close to
      the international level. The legal management system of POPs can be divided into
      four facets, including 3 regulations, 6 ordinances, and 20 standards. However, on
      the whole, most of the existing regulations do not refer to POPs directly. Only
      some clauses mention POPs and lack pertinent, explicit statements on POP
      pollution and control. Legislation is urgently needed for more effective
      environmental management to enhance POP control.

PMID- 15982741
TI  - Monitoring transitional waters using reduced benthic assemblages.
AB  - In this study, the use of reduced assemblages of benthic invertebrate taxa is
      proposed to describe similarity relationships between samples from transitional
      environments. A data set from four different studies, made up of 641 samples for
      a total 203 species, was analysed using permutation randomisation tests in order
      to extract a pool of taxa able to approximate the full set of species. The
      identified "operational set", comprising 19 taxa, was capable of adequately
      reproduce similarity relationships between samples (Rho>0.90, p<0.001). All
      selected taxa were easily extractable from the samples and easy identifiable by
      non-specialised technicians; these characteristics were considered appropriate
      for the development of rapid and cost-effective monitoring procedures based on
      benthic invertebrate assemblages.

PMID- 15982742
TI  - Neuroprotection from soman-induced seizures in the rodent: evaluation with
      diffusion- and T2-weighted magnetic resonance imaging.
AB  - Exposure to the organophosphate nerve agent soman produces seizures that in turn
      lead to neuropathology. This study describes the temporal and spatial evolution
      of brain pathology following soman-induced convulsions and the attenuation of
      these alterations after neuroprotective intervention with magnetic resonance
      imaging (MRI). Neuroimaging 12 h after soman exposure, the hippocampus and
      thalamus exhibited significant decreases (23%) in apparent diffusion coefficients
      (ADC). These acute effects were resolved by 7 days. In addition, T2 measurements
      declined significantly at 12 h (37%) returning to near normal values by 24 h.
      Histopathological analyses confirmed moderate cell loss within the hippocampus
      and piriform cortex. Together these findings suggest that initial cell death was
      resolved through regional cellular remodeling. Pharmacological countermeasures
      were administered in the form of diazepam, a benzodiazepine anticonvulsant, or
      gacyclidine (GK-11), an anti-glutamatergic compound. Diazepam therapy applied
      immediately after soman exposure prevented acute ADC changes. However the
      presence of edema, using T2 measurements, was detected at 3 h within the
      retrosplenial, amygdala and piriform cortices and at 12 h in the thalamus (34%
      below normal). GK-11 therapy appeared to prevent most of these changes. However
      at 7 days after soman, a decrease (17%) in ADC was observed in the piriform
      cortex. Pathology was confined to the piriform cortex suggesting that this region
      is more difficult to protect. This is the first report that provides temporal and
      spatial resolution using MRI with histological correlation of pharmacological
      interventions against soman-mediated seizure-induced neuropathology.

PMID- 15982743
TI  - Why don't we just do what we have to do?

PMID- 15982744
TI  - Human polyomaviruses and brain tumors.
AB  - Polyomaviruses are DNA tumor viruses with small circular genomes. Three
      polyomaviruses have captured attention with regard to their potential role in the
      development of human brain tumors: JC virus (JCV), BK virus (BKV), and simian
      vacuolating virus 40 (SV40). JCV is a neurotropic polyomavirus that is the
      etiologic agent of progressive multifocal leukoencephalopathy (PML), a fatal
      demyelinating disease of the central nervous system occurring mainly in AIDS
      patients. BKV is the causative agent of polyomavirus-associated nephropathy (PVN)
      which occurs after renal transplantation when BKV reactivates from a latent state
      during immunosuppressive therapy to cause allograft failure. SV40, originating in
      rhesus monkeys, gained notoriety when it entered the human population via
      contaminated polio vaccines. All three viruses are highly oncogenic when injected
      into the brain of experimental animals. Reports indicate that these viruses,
      especially JCV, are associated with brain tumors and other cancers in humans as
      evidenced from the analysis of clinical samples for the presence of viral DNA
      sequences and expression of viral proteins. Human polyomaviruses encode three non
      capsid regulatory proteins: large T-antigen, small t-antigen, and agnoprotein.
      These proteins interact with a number of cellular target proteins to exert
      effects that dysregulate pathways involved in the control of various host cell
      functions including the cell cycle, DNA repair, and others. In this review, we
      describe the three polyomaviruses, their abilities to cause brain and other
      tumors in experimental animals, the evidence for an association with human brain
      tumors, and the latest findings on the molecular mechanisms of their actions.

PMID- 15982745
TI  - Detection of neuronal growth inhibitory factor (metallothionein-3) in
      polyacrylamide gels and by Western blot analysis.
AB  - Neuronal growth inhibitory factor (GIF) is a small cysteine-rich metal binding
      protein downregulated in Alzheimer's disease. The protein belongs to the
      superfamily of metallothioneins (MTs) and was classified as MT-3. Although first
      identified as a brain specific protein, several reports now indicate a
      substantially broader expression pattern. However, currently available detection
      methods for MT-3 show low sensitivity in gel electrophoresis and Western blot. We
      have developed a fast and sensitive method for MT-3 detection in SDS-PAGE
      (detection limit approximately 10 ng) and Western blot (detection limit
      approximately 1 ng). The method is based on the chemical modification of cysteine
      residues with the dye monobromobimane and an improved blotting protocol.

PMID- 15982746
TI  - Comorbid depression in obsessive compulsive disorder (OCD): symptomatic
      differences to major depressive disorder.
AB  - In this study, we compared the depressive symptom profile of a group of obsessive
      compulsive disorder (OCD) patients, with comorbid depression, to a group of
      patients with major depressive disorder (MDD). The two groups (n=52 per group)
      were pair-wise matched on severity of depression as measured by the MADRS (mean
      24.3 for each group) and we examined between-group differences on the individual
      MADRS item scores. The OCD group was significantly more symptomatic on items 3
      (inner tension) and 9 (pessimistic thoughts) and significantly less symptomatic
      on items 4 (sleep) and 5 (appetite). We discuss these findings in the context of
      neurobiological bases for the two disorders.

PMID- 15982747
TI  - Treatment of generalized anxiety disorder with escitalopram: pooled results from
      double-blind, placebo-controlled trials.
AB  - BACKGROUND: Escitalopram 10 mg/day is an effective and well-tolerated
      antidepressant. Three randomized controlled trials recently evaluated the safety
      and efficacy of escitalopram in the treatment of generalized anxiety disorder
      (GAD). METHODS: The trial designs were virtually identical, allowing data to be
      pooled across studies. Male and female outpatients, ages 18-80 years, with DSM-IV
      defined GAD were randomized to double-blind treatment with escitalopram or
      placebo for 8 weeks. Escitalopram dose was fixed at 10 mg/day for the first 4
      weeks, after which increases to 20 mg/day were permitted. The primary efficacy
      variable was the mean change from baseline in total Hamilton Anxiety Scale (HAMA)
      score. RESULTS: Approximately 850 patients were randomized to double-blind
      treatment. In each individual study, escitalopram was significantly superior to
      placebo (p<0.05) as measured by change from baseline in HAMA score. By-visit
      analyses of data pooled across studies revealed significantly greater improvement
      (p<0.05) in the escitalopram group beginning at week 1 or 2 and continuing
      through week 8 for all primary and secondary efficacy variables. The mean change
      in HAMA total score from baseline to endpoint also was significantly greater for
      patients maintained at escitalopram 10 mg/day than for those receiving placebo.
      Escitalopram was generally well tolerated. LIMITATIONS: The studies included in
      this analysis were of short-term duration and excluded patients with significant
      medical and psychiatric comorbidities, such as major depressive disorder.
      CONCLUSION: Results from the individual trials and the pooled analysis
      demonstrate that escitalopram is effective and well tolerated for the treatment
      of GAD.

PMID- 15982748
TI  - Gender differences in depression: findings from the STAR*D study.
AB  - BACKGROUND: Epidemiologic research consistently reports gender differences in the
      rates and course of major depressive disorder (MDD). The STAR*D (Sequenced
      Treatment Alternatives to Relieve Depression) multicenter trial provides a unique
      opportunity to explore gender differences in outpatients with nonpsychotic MDD.
      METHODS: This sample included the first 1500 outpatients with MDD who enrolled in
      STAR*D. Nearly two-thirds of the sample (62.8%) were women. Baseline
      sociodemographic factors, comorbidities, and illness characteristics were
      analyzed by gender. RESULTS: Women (62.8% of the sample) had a younger age at
      onset of the first major depressive episode. They commonly reported concurrent
      symptoms consistent with anxiety disorders, somatoform disorder, and bulimia as
      well as atypical symptoms. Alcohol and drug abuses were more common in men.
      LIMITATIONS: This report is a subpopulation of the entire STAR*D sample. These
      exploratory analyses aimed to identify potential gender differences for further
      hypothesis testing. CONCLUSIONS: The gender-specific rate of MDD in this study
      population is proportional to rates found in community samples with a 1.7:1
      prevalence of MDD in women vs. men which argues against increased treatment
      seeking in women.

PMID- 15982749
TI  - Acute feed intake and acute-phase protein responses following a
      lipopolysaccharide challenge in pigs from two dam lines.
AB  - This study was conducted to evaluate the response of two dam lines of pigs to
      acute increases of LPS. Acute-phase proteins were also measured to determine
      their potential use as biological indicators of the immune response. Thirty-six
      pigs (initial body weight = 21.3 +/- 0.48 kg) were allotted by dam line (Lines 1
      and 2) and sex (castrates and gilts) to one of three LPS dose treatments and
      penned individually. Treatments were a single i.m. injection of 0 (LPS-0), 25
      (LPS-25) or 50 microg LPS/kg body weight (BW) (LPS-50). Acute changes in feed
      intake were related to a pre-injection baseline intake. Feeders were weighed
      daily to establish baseline feed intake (average daily feed intake -48 to 0 h
      prior to injection). The acute feed intake response (AFIR) was computed as the
      average daily feed intake 0-48 h after injection divided by baseline intake.
      Serum was harvested at time 0 and 48 h after injection. LPS-0 pigs grew faster
      and consumed more feed than the LPS-25 or LPS-50 pigs (0.79 kg/d versus 0.51 and
      0.50 kg/d; 1.15 kg/d versus 0.96 and 0.89 kg/d, respectively; P<0.001). The AFIR
      of Line 1 castrates and Line 2 gilts was similar for LPS-25 and LPS-50
      treatments, while Line 1 gilts and Line 2 castrates had decreased AFIR with
      increased LPS dose (sex x line x LPS, P<0.05). Three of 18 castrates died but no
      gilts died following the LPS challenge (P<0.10). Castrates had higher haptoglobin
      (Hpt) concentrations than gilts on d 0 (18.1 units of absorption/mg of protein
      versus 13.1 units of absorption/mg of protein; P<0.03). Line 1 pigs had higher C
      reactive protein (CRP) concentrations than Line 2 pigs (P<0.05) on d 0. LPS
      treatment did not change serum concentrations of CRP, Hpt or ceruloplasmin (Cp).
      However, the change in serum amyloid A (SAA) concentration decreased
      quadratically (from 0 to 48 h) with increasing LPS dose (P<0.02). This change in
      SAA was negatively correlated with the AFIR (r= -0.80; P<0.001). In general,
      castrates appear to be more sensitive to endotoxin challenges than gilts. Serum
      amyloid A, but not the other acute-phase proteins evaluated, was a good
      biological indicator of immune system activation following an acute
      lipopolysaccharide challenge when compared to the acute change in feed intake.

PMID- 15982750
TI  - In vitro IFN-gamma production by goat blood cells after stimulation with somatic
      and secreted Corynebacterium pseudotuberculosis antigens.
AB  - Corynebacterium pseudotuberculosis is the causal agent of caseous lymphadenitis,
      a chronic illness that attacks goats and sheep characterized by pyogranulomas
      formation in lymph nodes and organs. Regarding the current knowledge of the
      pathogenesis of the caseous lymphadenitis, there is evidence that besides the
      humoral response the induction of a durable cellular response is fundamental for
      its control. In this sense, research on antigens of C. pseudotuberculosis that
      are capable to inducing cellular immunity is an important step for the
      development of diagnosis tests and more efficient vaccines. In the present study,
      the interferon-gamma production in cultures of whole blood from infected goats
      stimulated with secreted bacterial antigen or somatic antigen were used to
      evaluate the cellular response. The results demonstrated a significant difference
      in the ability of the two antigens to induce a cellular response. That is, IFN
      gamma production was high with cells from infected animals in response to the
      secreted antigen while IFN-gamma production was low when somatic antigen was
      used. The concomitant use of these antigens with PWM also showed differences.
      That is, the secreted antigen increased the IFN-gamma production induced by PWM,
      while the somatic antigen seems not to have altered the response to PWM.

PMID- 15982751
TI  - Developmental differences between cation-independent and cation-dependent mannose
      6-phosphate receptors in rat brain at perinatal stages.
AB  - Mannose-6-phosphate receptors (MPRs) play a role in the selective transport of
      macromolecules bearing mannose-6-phosphate residue to lysosomes. To date, two
      types of MPRs have been described in most of cells and tissues: the cation
      dependent (CD-MPR) and cation-independent mannose-6-phosphate receptor (CI-MPR).
      In order to elucidate their possible role in the central nervous system, the
      expression and binding properties of both MPRs were studied in rat brain along
      perinatal development. It was observed that the expression of CI-MPR decreases
      progressively from fetuses to adults, while the CD-MPR increases around the 10th
      day of birth, and maintains these values up to adulthood. Binding assays showed
      differences in the Bmax and KD values between the ages studied, and they did not
      correlate with the expression levels of both MPRs. Variations in lysosomal enzyme
      activities and expression of phosphomannosylated ligands during development
      correlated more with CD-MPR than with CI-MPR expression. These results suggest
      that both receptors play a different role in rat brain during perinatal
      development, being CD-MPR mostly involved in lysosome maturation.

PMID- 15982752
TI  - Blocking of leukocyte accumulation in the cerebrospinal fluid augments bacteremia
      and increases lethality in experimental pneumococcal meningitis.
AB  - The role of leukocyte accumulation in the cerebrospinal fluid (CSF) in the
      evolution of the pathophysiological changes that occur in bacterial meningitis is
      unclear. Here, we investigate how leukocyte recruitment to the CSF, modulated by
      the leukocyte blocker fucoidin, affects the extent of brain damage and outcome in
      pneumococcal meningitis in rats treated with ceftriaxone from 28 h after
      infection. Rats treated with fucoidin from time of infection had an excess risk
      of a fatal outcome compared to rats not receiving fucoidin (25/63 versus 5/34,
      p=0.012), whereas the risk of cortical damage in surviving animals was comparable
      (16/44 versus 9/29, p=0.8). Pre-treatment with fucoidin attenuated CSF
      pleocytosis 24 h after infection (median 400 versus 800x10(6) cells/l, p=0.01)
      without affecting CSF bacterial counts (2.3x10(5) versus 3.6x10(5) CFU/ml,
      p=0.54). A significant increase in blood bacterial counts was found among rats
      pre-treated with fucoidin (median 9.6x10(2) versus 5.2x10(2) CFU/ml, p=0.03).
      Furthermore, blood bacterial count was found to be an important predictor of
      fatal outcome as shown by multivariate logistical regression analysis (OR 4.43,
      95% CI [1.16-17.0] p=0.03). In summary, blocking leukocyte entry to the central
      nervous system in experimental pneumococcal meningitis compromises the survival
      prognosis but does not affect the risk of brain damage or level of infection in
      this compartment. Conversely, poorer prognosis was associated with an increase in
      bacterial load in blood, suggesting that leukocyte blockage affects the host's
      ability to control systemic infection.

PMID- 15982753
TI  - Subcortical loops through the basal ganglia.
AB  - Parallel, largely segregated, closed-loop projections are an important component
      of cortical-basal ganglia-cortical connectional architecture. Here, we present
      the hypothesis that such loops involving the neocortex are neither novel nor the
      first evolutionary example of closed-loop architecture involving the basal
      ganglia. Specifically, we propose that a phylogenetically older, closed-loop
      series of subcortical connections exists between the basal ganglia and brainstem
      sensorimotor structures, a good example of which is the midbrain superior
      colliculus. Insofar as this organization represents a general feature of brain
      architecture, cortical and subcortical inputs to the basal ganglia might act
      independently, co-operatively or competitively to influence the mechanisms of
      action selection.

PMID- 15982754
TI  - The many faces of CREB.
AB  - The transcription factor CREB is best known for its involvement in learning and
      memory. However, emerging evidence suggests that CREB activity has very different
      roles--sometimes beneficial, sometimes detrimental--depending on the brain region
      involved. Induction of CREB in the hippocampus by antidepressant treatments could
      contribute to their therapeutic efficacy. By contrast, activation of CREB in the
      nucleus accumbens and several other regions by drugs of abuse or stress mediates
      certain aspects of drug addiction, and depressive and anxiety-like behaviors.
      These complexities suggest that strategies that exploit regional differences in
      upstream factors or that target specific CREB-regulated genes, rather than CREB
      itself, could make a promising contribution to the treatment of neuropsychiatric
      conditions.

PMID- 15982755
TI  - Comparison of polychlorinated biphenyl (PCB) induced effects on innate immune
      functions in harbour and grey seals.
AB  - Polychlorinated biphenyls (PCBs) are known to have detrimental effects on the
      innate immune system of several mammalian species. Top predators such as marine
      mammals may be badly affected as PCBs can bioaccumulate in their blubber to high
      concentrations and previous studies have suggested that harbour seals may be
      particularly vulnerable to the immunotoxic effects of such contaminants. To
      investigate the effects of PCBs on innate immune functions in phocid seals, blood
      samples were collected from harbour and grey seals and exposed in vitro to a
      mixture of Aroclors. Separated mononuclear (PBMCs) and polymorphonuclear (PMNCs)
      leukocytes from each species were incubated with Aroclors (at 3 and 30 ngml(-1))
      for 3 and 24 h incubation periods, after which phagocytosis, respiratory burst
      and cytotoxic activity were measured. The phagocytic activity of harbour seal
      PMNCs was decreased at both incubation times and at both Aroclor concentrations
      tested, but there was no effect on the grey seals. Similarly, the respiratory
      burst activity of harbour seals was decreased at both incubation times, but only
      at the higher concentration used. There were no differences in the cytotoxic
      activity of the PBMCs with respect to incubation times or concentrations in
      either species. However, differences were observed in the level of cytotoxic
      activity against YAC-1 target cells, with the grey seal PBMCs showing higher
      levels of activity. The observed differences in phagocytosis, respiratory burst
      and cytotoxic activity of the leukocytes following incubation with PCBs may have
      implications for the previously recorded differences in disease susceptibility
      between grey and harbour seals.

PMID- 15982756
TI  - Dose-response for inhibition by amylin of cholecystokinin-stimulated secretion of
      amylase and lipase in rats.
AB  - BACKGROUND AND AIMS: The neuroendocrine hormone amylin, cosecreted with insulin
      from pancreatic beta-cells in response to nutrient ingestion, has several
      physiologic actions to limit the rate of nutrient uptake, including the slowing
      of gastric emptying. METHODS: To investigate whether amylin might modulate
      digestive enzyme secretion from the exocrine pancreas, anesthetized Sprague
      Dawley rats were cannulated via the pancreatic duct and the secretory response
      (flow, amylase and lipase) to cholecystokinin (1 microg s.c.) was measured in the
      absence and in the presence of 0.1, 0.3 and 1 microg s.c. doses of amylin.
      RESULTS: Amylin alone did not affect pancreatic secretion, but it dose
      dependently inhibited cholecystokinin-stimulated amylase secretion by up to 58%
      and lipase secretion by up to 67%. The ED50's for these responses were 0.21
      microg+/-0.18 log and 0.11 microg+/-0.05 log, respectively, doses that result in
      excursions of plasma amylin concentration that are within the reported
      physiological range. Amylin did not evoke cell signalling in the Ar42j model of
      pancreatic acinar cells, and responses to amylin were not observed in either
      Ar42j cells or isolated pancreatic acini in a microphysiometer indicating that
      the effect of amylin was indirect. CONCLUSIONS: Inhibition of stimulated
      pancreatic enzyme secretion is likely to be a physiological, extrapancreatic,
      action of amylin. Amylinergic mechanisms modulating both gastric emptying and
      pancreatic enzyme secretion may thus match, respectively, the appearance of
      substrate and enzymes in the gut lumen.

PMID- 15982757
TI  - A novel PDIP1-related protein, KCTD10, that interacts with proliferating cell
      nuclear antigen and DNA polymerase delta.
AB  - Rat potassium channel tetramerisation domain-containing 10 (KCTD10) gene was
      cloned and identified as a novel member of polymerase delta-interacting protein 1
      (PDIP1) gene family. Rat KCTD10 is highly expressed in lung and moderately
      expressed in heart and testis. KCTD10 shares significant similarity in amino acid
      sequence to PDIP1 and can interact with the small subunit of DNA polymerase delta
      and PCNA as PDIP1 does. Like PDIP1, the expression of KCTD10 gene can be induced
      by TNF-alpha in NIH3T3 cells.

PMID- 15982758
TI  - Emergency department fall-related presentations do not trigger fall risk
      assessment: a gap in care of high-risk outpatient fallers.
AB  - We wanted to determine whether women aged 70 years and older, who presented to
      the emergency department (ED) with a fall and injury, received guideline care
      within 18 months of presentation. Women aged 70 years and older who presented to
      the ED with a fall were recorded prospectively from August 1, 2001 to May 1, 2002
      (n=226). Structured telephone interviews were performed 18 months after the ED
      fall to obtain details of patient management (n=63). The most frequently reported
      referral was to the family physician (32%) and to physiotherapy (24%). We
      concluded that most older women who presented to the ED with a fall did not
      appear to be receiving current guideline care. We propose that future research
      use a prospective study design to assess whether or not guideline care is being
      delivered by a variety of health care providers after the patients leave the ED.

PMID- 15982759
TI  - New diagnostic technique in multi-slice computed tomography for in-stent
      restenosis: pixel count method.
AB  - OBJECTIVES: A diagnostic technique to objectively determine coronary in-stent
      stenosis was developed with multi(16)-slice computed tomography (MSCT), and it
      was compared with coronary angiography (CAG) in clinical cases. BACKGROUND: MSCT
      is expected to replace coronary angiography as a new non-invasive examination.
      Evaluation of highly calcified or in-stent lesions with CT is generally thought
      to be difficult. METHODS: Twenty lesions among 16 consecutive patients that were
      implanted with coronary stents were examined with both MSCT and CAG at follow-up.
      The minor axis cross sections of the stents were reconstructed at intervals of
      1.5 mm with multiplanar reformation (MPR). The pixel with a higher CT value than
      the lowest CT value in the standard cross section at the proximal site out of
      stent was counted to determine the presence/absence of a stenotic lesion.
      RESULTS: Among 20 lesions, one case was not able to be evaluated with MSCT. MSCT
      correctly detected 3 of 4 cases with in-stent stenosis (sensitivity 75%), and 14
      of 16 cases with no in-stent stenosis (specificity 88%, negative predictive value
      93%, positive predictive value 75%). If analysis was made per-artery, sensitivity
      and specificity were 100% (3 of 3) and 87% (13 of 15), respectively, for
      detection of in-stent stenosis. CONCLUSIONS: This study was performed to examine
      a unique diagnostic technique: pixel count method, for coronary in-stent stenosis
      with MSCT. It showed that the coronary in-stent stenosis could be determined when
      stent struts were clearly imaged. Further examination is required with various
      stents, especially those with a diameter of 3.0 mm or smaller.

PMID- 15982760
TI  - Closure of atrial septal defect in the adult. Cardiac remodeling is an early
      event.
AB  - BACKGROUND: Study aimed to describe the extent and the temporal profile of
      cardiac remodeling after atrial septal defect closure in the adult. METHODS:
      Prospective and longitudinal echocardiographic assessment of right and left heart
      size before and after (1 day-1 week/1/4/12 months) surgical or catheter-based
      atrial septal closure in 39 adults (age 54+/-15 years). RESULTS: Right
      ventricular and atrial sizes were markedly reduced, left ventricular size
      increased and left atrial size remained unchanged after closure. Older age and a
      history of atrial fibrillation reduced the potential to normalize right and left
      atrial size after closure. The greater part of the changes occurred very early,
      in the 1st day/1st week. From then on the speed of change gradually diminished
      and after 4 months no important changes were observed. The mode of closure did
      not influence the degree or the pace of the remodeling. CONCLUSION: Cardiac
      remodeling after atrial septal closure in the adult is a common and early event
      that seems by and large completed within the first half year after closure. The
      ventricles seem to have a higher capacity of remodeling than the atria in this
      setting. The mode of closure does not seem to significantly impact remodeling.

PMID- 15982761
TI  - Covered stent for closure of symptomatic plexus-like coronary fistula.
AB  - Coronary to pulmonary artery fistula are the most frequent congenital anomalies
      of the coronary arteries. When they are symptomatic they have to be treated in
      order to prevent complications such as sudden death or myocardial infarction.
      Surgery is the gold standard for their closure. However an increasing number of
      reports have shown that interventional cardiology could be a safe and efficient
      alternative. Plexus-like fistula are composed of multiples and tortuous branches
      that make them difficult to treat. We report the use of polytetrafluoroethylene
      covered (PTFE) stent to cure a plexus-like coronary to pulmonary artery fistula,
      without associated atherosclerosis, responsible for myocardial ischemia.

PMID- 15982762
TI  - Risk factors for interdigital dermatitis and heel erosion in dairy cows kept in
      cubicle houses in The Netherlands.
AB  - Risk factors concerning both the pasture and housing seasons for interdigital
      dermatitis and heel-horn erosion (IDHE) were studied in dairy cows in a cross
      sectional study in The Netherlands. The study population included 2,326 cows (41
      herds) and 2,751 cows (46 herds) for the pasture and housing seasons,
      respectively. Of these animals, 545 (23%) showed serious lesions of IDHE (stages
      2 and 3) at the end of the pasture season and 1,269 (46%) during housing.
      Logistic regression of the pasture study indicated that increased parity, solid
      concrete floor, restricted grazing time, and herd trimming at long intervals were
      associated with an increased odds of IDHE, while dry cows and lactating cows
      within 30 days after calving as well as cows on a slatted floor with manure
      scraper, and grassland with mixed type of soil were associated with lower odds.
      In the housing study, odds of IDHE increased with parity, administering low- or
      medium-energy roughage, and introduction of dry cows into the lactating herd at
      >2 weeks before calving. The presence of long cubicles, knee-bumpers installed in
      cubicles as well as rearing calves and heifers within the dairy cows'
      accommodation decreased the odds of IDHE.

PMID- 15982763
TI  - 5th International symposium on the interface between analytical chemistry and
      microbiology-April 19th to 21st, 2004. Hosted at Pacific Northwest National
      Laboratory.

PMID- 15982764
TI  - Quenching of microbial samples for increased reliability of microarray data.
AB  - Messenger RNA levels change on a minutes scale due to both degradation and de
      novo transcription. Consequently, alterations in the transcript profiles that are
      not representative for the condition of interest are easily introduced during
      sample harvesting and work-up. In order to avoid these unwanted changes we have
      validated a -45 degrees C methanol-based quenching method for obtaining reliable
      and reproducible 'snapshot' samples of Lactobacillus plantarum cells for
      transcriptome analyses. Transcript profiles of cells harvested with the quenching
      method were compared with transcript profiles of cells that were harvested
      according to two different commonly applied protocols. Significant differences
      between the transcript profiles of cells harvested by the different methods from
      the same steady-state culture were observed. In total, 42 genes or operons were
      identified from which the transcript levels were altered when the cells were not
      immediately quenched upon harvesting. Among these, several have previously been
      associated with cold-shock response. Furthermore, the reproducibility of
      transcript profiles improved, as indicated by the fact that the variation in the
      data sets obtained from the quenched cells was smaller than in the data sets
      obtained from the cells that were harvested under non-quenched conditions.

PMID- 15982765
TI  - Image analysis for quantification of bacterial rock weathering.
AB  - A fast, quantitative image analysis technique was developed to assess potential
      rock weathering by bacteria. The technique is based on reduction in the surface
      area of rock particles and counting the relative increase in the number of small
      particles in ground rock slurries. This was done by recording changes in ground
      rock samples with an electronic image analyzing process. The slurries were
      previously amended with three carbon sources, ground to a uniform particle size
      and incubated with rock weathering bacteria for 28 days. The technique was
      developed and tested, using two rock-weathering bacteria Pseudomonas putida R-20
      and Azospirillum brasilense Cd on marble, granite, apatite, quartz, limestone,
      and volcanic rock as substrates. The image analyzer processed large number of
      particles (10(7)-10(8) per sample), so that the weathering capacity of bacteria
      can be detected.

PMID- 15982766
TI  - Site-directed genome modification: nucleic acid and protein modules for targeted
      integration and gene correction.
AB  - A variety of technological advances in recent years have made permanent genetic
      manipulation of an organism a technical possibility. As the details of natural
      biological processes for genome modification are elucidated, the enzymes
      catalyzing these events (transposases, recombinases, integrases and DNA repair
      enzymes) are being harnessed or modified for the purpose of intentional gene
      modification. Targeted integration and gene repair can be mediated by the DNA
      targeting specificity inherent to a particular enzyme, or rely on user-designed
      specificities. Integration sites can be defined by using DNA base-pairing or
      protein-DNA interaction as a means of targeting. This review will describe recent
      progress in the development of 'user-targetable' systems, particularly
      highlighting the application of custom DNA-binding proteins or nucleic acid
      homology to confer specificity.

PMID- 15982767
TI  - Thalamocortical theta coherence in neurological patients at rest and during a
      working memory task.
AB  - We simultaneously recorded the local field potential (LFP) in the thalamus and
      the electroencephalogram (EEG) on the scalp of 5 patients suffering from
      neurogenic pain, epilepsy and movement disorders. In an earlier study [], we have
      investigated the slowing of EEG and the high thalamocortical coherence in the
      framework of thalamocortical dysrhythmia, the common underlying pathophysiology.
      The current study focuses on the effects of different cognitive conditions. When
      patients rested with eyes closed, a theta peak dominated the EEG spectra. The
      peak height was reduced upon opening the eyes, reminiscent of the classical alpha
      blocking. This peak reduction also appeared in the thalamic LFP recording. When
      patients activated their working memory by counting backwards, the theta peak
      increased in scalp EEG or in the LFP recorded in thalamic nuclei VA/VL. The
      coherence estimates between EEG and LFP ranged between 21% and 76% for different
      patients and cognitive conditions (mean: 50%). The involvement of both cortex and
      thalamus in working memory and the high thalamocortical coherence underline, in
      addition to cortico-cortical interactions, the importance of thalamocortical
      modules in the generation of higher cognitive functions.

PMID- 15982768
TI  - Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels.
AB  - Endogenous polyamines like spermine are known to have four distinct effects on
      recombinant N-methyl-d-aspartate (NMDA) receptor channels: voltage-dependent
      inhibition, glycine-dependent stimulation, glycine-independent stimulation and
      decreased affinity to the agonist (l-glutamate). These effects are highly
      dependent on the constituting epsilon subunits (epsilon1-epsilon4) of the
      recombinant NMDA receptor channels. Agmatine reportedly inhibits native NMDA
      receptor channels in cultured hippocampal neurons. In the present investigation,
      the effects of agmatine on the epsilon/zeta heteromeric NMDA receptor channels
      expressed in Xenopus laevis oocytes were examined using the two-electrode voltage
      clamp method. Agmatine inhibited the four epsilon/zeta (epsilon1/zeta1,
      epsilon2/zeta1, epsilon3/zeta1 and epsilon4/zeta1) channels with similar
      sensitivity (an IC50 value of about 300microM at -70mV). This effect was
      dependent on the membrane potential and was more pronounced at hyperpolarized
      membrane potentials (voltage-dependent inhibition). Agmatine did not exhibit
      other stimulatory (glycine-dependent and -independent effects) or inhibitory
      (decreased affinity to l-glutamate) effects. These properties are similar to the
      pharmacological profile of well-characterized NMDA receptor channel blockers like
      phencyclidine and ketamine. Thus, regarding the effects on the NMDA receptor
      channels, agmatine is not like other endogenous polyamines rather it acts as a
      channel blocker.

PMID- 15982769
TI  - Development and evaluation of a Mycobacterium avium subspecies paratuberculosis
      (MAP) specific multiplex PCR assay.
AB  - There are specificity questions inherent in most of the current PCR systems that
      amplify the MAP IS900 sequence as an indicator for Mycobacterium avium subspecies
      paratuberculosis (MAP) presence due to false positives associated with IS900-like
      sequences that exists in other Mycobacterium species besides MAP. We developed a
      multiplex PCR system designed to enhance specificity for MAP detection in a
      single PCR reaction. This PCR assay co-amplifies the mycobacterium species 16S
      rRNA gene, MAP IS900 and f57 sequences. The assay incorporates an internal PCR
      amplification control (IC) template system enabling PCR amplification conditions
      to be assessed in each reaction. The assay's specificity was confirmed by testing
      10 isolates of MAP and 59 isolates of other bacterial species. In parallel we
      also applied on the same samples, one of the established nested PCR systems that
      targets only the IS900 sequence. The multiplex PCR assay was highly specific for
      MAP, the nested PCR system was also positive with several other mycobacterium
      species. In this context, we report for the first time false positive IS900 PCR
      signals in Mycobacterium chelonae, Mycobacterium terrae and Mycobacterium xenopi
      strains associated with one of the established PCR systems widely used for MAP
      detection. Finally, the potential application of this multiplex PCR system in
      milk analysis is demonstrated through analysis of raw milk samples artificially
      contaminated with MAP.

PMID- 15982770
TI  - Fatty acid composition, cell morphology and responses to challenge by organic
      acid and sodium chloride of heat-shocked Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus 690, a clinical strain, was subjected to heat shock at 42
      degrees C for 45 min. The fatty acid profile and recovery of the heat-shocked
      cells of V. parahaemolyticus on TSA-3.0% NaCl, APS agar (Alkaline peptone salt
      broth supplemented with 1.5% agar) and TCBS (Thiosulfate-citrate-bile salts
      sucrose agar) were compared with those of the nonheat-shocked cells. Furthermore,
      the morphology of V. parahaemolyticus and survival in the presence of various
      organic acids (25 mM acetic acid, lactic acid, citric acid or tartaric acid) and
      NaCl (0.1% and 20.0%) as influenced by heat shock treatment were also
      investigated. It was found that heat shock caused a change in the proportions of
      the unsaturated and saturated fatty acid. The ratio of saturated fatty acids to
      unsaturated fatty acids observed on heat-shocked V. parahaemolyticus cells was
      significantly (p<0.05) higher than that on the control cells. Extensive cell-wall
      pitting and cell disruption, representing cell-surface damage, were also observed
      on the cells which were subjected to heat shock treatment. Recovery of heat
      shocked cells of V. parahaemolyticus was significantly less on TCBS and APS agar
      than on TSA-3.0% NaCl. Heat shock decreased the tolerance of V. parahaemolyticus
      to organic acids. The extent of decreased acid tolerance observed on heat-shocked
      cells varied with the organic acid tested. While heat shock increased the
      survival of V. parahaemolyticus in the presence of 0.1% NaCl and made the test
      organism more susceptible to 20.0% NaCl than the control cells.

PMID- 15982771
TI  - Relevant aspects of Arcobacter spp. as potential foodborne pathogen.
AB  - Arcobacter species are Gram-negative spiral-shaped organisms belonging to the
      family Campylobacteraceae that can grow microaerobically or aerobically. The
      Arcobacter organisms also have the ability to grow at 15 degrees C, which is a
      distinctive feature that differentiates Arcobacter species from Campylobacter
      species. Cultural detection of Arcobacter is generally performed by an enrichment
      step and takes 4 to 5 days. In the last few years, several studies comparing
      different culture-based protocols have been published. Furthermore, DNA-based
      assays have also been established for rapid and specific identification of
      Arcobacter spp. Recent evidence suggests that Arcobacter, especially A. Butzleri,
      may be involved in human enteric diseases. Moreover, A. butzleri has also
      occasionally been found in cases of human extraintestinal diseases. However, up
      to now, little is known about the mechanisms of pathogenicity or potential
      virulence factors of Arcobacter spp. There is evidence that livestock animals may
      be a significant reservoir of Arcobacter spp. and over the last few years, the
      presence of these organisms in raw meat products as well as in surface and ground
      water has received increasing attention. In view of control measures to be used
      to prevent or to eliminate the hazard of Arcobacter spp. in food, several
      treatments have been evaluated for their effectiveness. While the role of
      Arcobacter spp. in human disease awaits further evaluation, a precautionary
      approach is advisable. Measures aimed at reduction or eradication of Arcobacter
      from the human food chain should be encouraged. With this article, we review the
      recent literature on this organism with a special emphasis on the information
      relevant to food safety.

PMID- 15982772
TI  - A continuous thermal lysis procedure for the large-scale preparation of plasmid
      DNA.
AB  - There is an increasing interest and need for the development of scaleable process
      for the preparation of plasmid DNA for vaccines and gene therapy. In this report,
      we describe a streamline modified process of plasmid extraction based on boiling
      lysis in order to simplify the operation and process large volumes of Escherichia
      coli cultures. The bacteria, harvested using a hollow fiber cartridge after
      fermentation, were treated with lysozyme at 37 degrees C prior to passing through
      a heat-exchanger coil. Subsequently, the supernatant was separated from lysed
      bacteria using a 65 microm nylon filter. The employment of a peristaltic pump and
      two heating coils at constant temperature without the use of centrifugation
      enabled the process protocol to be constant and controllable. A relatively low
      lysis temperature of approximately 70-80 degrees C and a buffer modified for the
      high-density cultures were also optimized for the process. Prior to thermal
      lysis, a pre-treatment step with the lysozyme for 20 min at 37 degrees C was one
      of the crucial steps contributing to the high plasmid quantity and quality from
      batch to batch. After harvesting 17 L of E. coli cultures (OD600 = 50), the
      plasmid can be extracted within 45 min with this streamline protocol. The plasmid
      yields are approximately 100mg/L culture, which makes it attractive and promising
      for the large-scale preparation of plasmid.

PMID- 15982773
TI  - Development of a S. cerevisiae whole cell biocatalyst for in vitro sialylation of
      oligosaccharides.
AB  - Absence of sialylation on recombinant glycoproteins compromises their efficacy as
      therapeutic agents, as it results in rapid clearance from the human bloodstream.
      To circumvent this, several strategies are followed, including the implementation
      of a post-secretion glycosylation step. In this paper we describe the engineering
      of yeast cells expressing active surface exposed Trypanosoma cruzi trans
      sialidase (TS) fused to the yeast Aga2 protein, and the use of this yeast in the
      sialylation of synthetic oligosaccharides. In an attempt to improve overall
      protein accessibility on the yeast surface, we abolished hyperglycosylation on
      the yeast cell wall proteins. This was achieved by disrupting the OCH1 gene of
      the TS surface expressing strain, which resulted in increased enzymatic activity.
      Using a fluorescence-based activity assay and DSA-FACE structural analysis, we
      obtained almost complete conversion to a fully sialylated acceptor, whereas in
      the wild type situation this conversion was only partial. Increasing protein
      accessibility on the yeast surface by modifying the glycosylation content thus
      proved to be a valuable approach in increasing the cell wall associated activity
      of an immobilised enzyme, hence resulting in a more effective biocatalyst system.

PMID- 15982775
TI  - Spontaneous tail length variation in a Salmonella myovirus.
AB  - Salmonella phage SPT-1, a member of the Myoviridae family and a relative of phage
      O1, produces abnormally long tails with coordinate variations of sheath and core
      length. The length of abnormal tails varies between 140 and 445 nm.

PMID- 15982776
TI  - Nitric oxide donors can enhance the intestinal transport and absorption of
      insulin and [Asu(1,7)]-eel calcitonin in rats.
AB  - The characteristics of three NO donors, 3-(2-hydroxy-1-(1-methylethyl)-2
      nitrosohydrazino)-1-propanamine (NOC5), N-ethyl-2-(1-ethyl-2-hydroxy-2
      nitrosohydrazino)-ethanamine (NOC12) and S-nitroso-N-acetyl-DL-penicillamine
      (SNAP) as absorption enhancers for peptide drugs were examined in rats using a
      modified Ussing chamber method and an in situ closed loop method. Insulin and
      [Asu(1,7)]-eel calcitonin (ECT) were used as a model drug to investigate the
      effectiveness of the tested enhancers. The NO donors significantly increased the
      in vitro permeability of insulin across all intestinal membranes. In general, the
      absorption enhancement effects of these NO donors were greater in the colon than
      those in the jejunum and ileum. Of these NO donors, SNAP was the most effective
      enhancer. Their effects were concentration-dependent over the range of 0.01 to
      0.1 mM. However, 0.1 mM NO donors had almost the same effects as those at 1 mM
      concentration. The absorption-enhancing effects of the three NO donors were
      inhibited by the co-administration of 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazole-1-oxyl 3-oxide, sodium salt (carboxy-PTIO), an NO scavenger,
      suggesting that NO might be responsible for the efficacy of NO donors. In the in
      situ closed loop experiments, the three enhancers significantly improved the
      pharmacological availability % (PA%) of insulin in the small and large intestine.
      Similar results were also obtained when NO donors were added to ECT solution by
      an in situ closed loop method. These results suggest that NO donors possess
      excellent effectiveness for the use as absorption enhancers of peptide drugs and
      they are very effective at lower concentrations compared to the conventional
      enhancers.

PMID- 15982777
TI  - On the study of BSA-loaded calcium-deficient hydroxyapatite nano-carriers for
      controlled drug delivery.
AB  - Calcium-deficient hydroxyapatite (CDHA) nano-crystals incorporated with bovine
      serum albumin (BSA) to form BSA-loaded nano-carriers were synthesized via both in
      situ and ex-situ processes. Amount of BSA uptake by the CDHA nano-crystals and
      subsequent release behaviors of the BSA-loaded nano-carriers were investigated.
      The amount of BSA uptake by CDHA decreases with increasing pH but a larger amount
      was observed in the ex-situ compared to in-situ process above pH=8.0. The release
      profile showed a bursting behavior for the nano-carrier prepared via the ex-situ
      process, which is probably due to the desorption of BSA molecules. In contrast,
      for the sample synthesized via the in-situ process at a higher pH level, a slower
      release profile without bursting behavior due to the dissolution of the BSA
      incorporated CDHA crystal is seen from high solution TEM that indicates different
      extent of interaction between BSA and CDHA. On the other hand, for the nano
      carriers prepared via the same process at lower pH level, a two-stage release
      profile was detected. An initial bursting release is due to the desorption of BSA
      from the CDHA surface, followed by a slow release as a result of the dissolution
      of the BSA-incorporated nano-crystals along its c-axis direction.

PMID- 15982778
TI  - DNA electrotransfer into the skin using a combination of one high- and one low
      voltage pulse.
AB  - Electroporation is an effective alternative to viral methods to significantly
      improve DNA transfection after intradermal and topical delivery. The aim of the
      study was to check whether a combination of a short high-voltage pulse (HV) to
      permeabilize the skin cells and a long low-voltage pulse (LV) to transfer DNA by
      electrophoresis was more efficient to enhance DNA expression than conventional
      repeated HV or LV pulses alone after intradermal injection of DNA plasmid. GFP
      and luciferase expressions in the skin were enhanced by HV+LV protocol as
      compared to HV or LV pulses alone. The expression lasted for up to 10 days.
      Consistently, HV+LV protocol induced a higher Th2 immune response against
      ovalbumin than HV or LV pulses. Standard methods were used to assess the effect
      of electric pulses on skin: the application of a combination of HV and LV pulses
      on rat skin fold delivered by plate electrodes was well tolerated. These data
      demonstrate that a combination of one HV (700 to 1000 V/cm; 100 micros) followed
      by one LV (140 to 200 V/cm; 400 ms) is an efficient electroporation protocol to
      enhance DNA expression in the skin.

PMID- 15982779
TI  - Providing guidance to the NHS: The Scottish Medicines Consortium and the National
      Institute for Clinical Excellence compared.
AB  - There is wide acceptance that cost-effectiveness is a relevant consideration when
      deciding which treatments to make available in publicly funded health services.
      An unresolved issue concerns the timing and the extent of such evaluations. The
      United Kingdom provides examples of two distinct approaches. The Scottish
      Medicines Consortium (SMC) provides guidance to the NHS in Scotland based on a
      rapid early review of the evidence. The National Institute for Health and
      Clinical Excellence (NICE) provides guidance to the NHS in England and Wales
      based on a later, more extensive review of the evidence. This paper explores how
      the difference in approach affects the role of the pharmaceutical industry,
      clinical experts and other stakeholders. It compares the guidance produced when
      both bodies have evaluated the same medicines. It addresses the general question
      of when to assess the cost-effectiveness of medicines. It concludes that there
      are important differences between the approaches of SMC and NICE, relating
      primarily to the timing of the review of evidence on clinical and cost
      effectiveness. The difference in timing means that the activities of the two
      bodies are to a large extent complementary.

PMID- 15982780
TI  - Different types and aspects of quality systems and their implications. A thematic
      comparison of seven quality systems at a university hospital.
AB  - Policy makers and managers face a difficult challenge in keeping up with the
      changing organisations and methods of health care. Organised systematic quality
      work, that is, quality systems, can make this task easier. The aim here was to
      study different quality systems, identify common characteristics, find types of
      quality systems and discuss the practical implications of the results. The study
      was designed as a qualitative study of seven clinics with quality systems at a
      large university hospital in Sweden. Purposefully selected, 19 managers or
      quality co-ordinators were interviewed. The interviews were audio taped,
      transcribed verbatim and analysed thematically. Six organisational aspects were
      present in the interviews: resources, administration, culture, co-operation, goal
      achievement and development of competence. The aspects were used to categorise
      the clinics' systems into three types: local, centralised and integrated systems.
      The responses indicated that local systems had a decentralised organisation,
      allowing for a high degree of adaptability. Centralised systems were reported to
      be more top-down orientated, allowing for a highly predictable output. Integrated
      systems were reported to have a management style that emphasized co-operation,
      allowing for both good adaptability and predictability. Policy makers and
      managers could use the described aspects and types of quality systems to help
      decide what type of quality system to implement in a specific setting, as a base
      line for evaluation, or as a framework for developing existing quality systems.

PMID- 15982781
TI  - Discovering functional relationships: biochemistry versus genetics.
AB  - Biochemists and geneticists, represented by Doug and Bill in classic essays, have
      long debated the merits of their methods. We revisited this issue using genomic
      data from the budding yeast, Saccharomyces cerevisiae, and found that genetic
      interactions outperformed protein interactions in predicting functional
      relationships between genes. However, when combined, these interaction types
      yielded superior performance, convincing Doug and Bill to call a truce.

PMID- 15982782
TI  - Two cysteine substitutions in the MC1R generate the blue variant of the Arctic
      fox (Alopex lagopus) and prevent expression of the white winter coat.
AB  - We have characterized two mutations in the MC1R gene of the blue variant of the
      arctic fox (Alopex lagopus) that both incorporate a novel cysteine residue into
      the receptor. A family study in farmed arctic foxes verified that the dominant
      expression of the blue color phenotype cosegregates completely with the allele
      harboring these two mutations. Additionally to the altered pigment synthesis, the
      blue fox allele suppresses the seasonal change in coat color found in the native
      arctic fox. Consequently, these findings suggest that the MC1R/agouti regulatory
      system is involved in the seasonal changes of coat color found in arctic fox.

PMID- 15982783
TI  - Expression of the human melanocortin-2 receptor in different eukaryotic cells.
AB  - The human melanocortin-2 receptor (hMC2R) is mainly present in the adrenal cortex
      and has been difficult to express in heterologous cells. The hMC2R fused to the
      EGFP at its C-terminus has been stably transfected in the murine M3 melanoma and
      HEK293 cells. In the M3 cells, the hMC2R-EGFP was well-addressed to the cell
      membrane and functional whereas in the HEK293 cells, the hMC2R-EGFP was retained
      intracellularly. These results suggest that some specific factors, missing in
      cells, which do not express any melanocortin receptor, are involved in the
      correct addressing of the hMC2R to the cell membrane.

PMID- 15982784
TI  - Dose-response effects of ectopic agouti protein on iron overload and age
      associated aspects of the Avy/a obese mouse phenome.
AB  - Isogenic and congenic offspring from matings of inbred black a/a dams by sibling
      (or non-sibling from another inbred strain) yellow agouti Avy/a sires provide an
      animal model of obese yellow agouti Avy/a and isogenic lean pseudoagouti Avy/a
      mice exhibiting two different in vivo concentrations (high, very low) of ectopic
      agouti protein (ASP) with congenic lean black a/a mice as null controls. This
      makes it possible to differentiate between the high and very low dose levels of
      ectopic ASP with respect to interactions with diverse physiological and molecular
      pathways. Assay of differential responses to 12 or 24 months of carbonyl iron
      overload assessed the possible suitability of this animal model for the study of
      hemochromatosis. Agouti A/a B6C3F1 mice were used as non-congenic null controls.
      The age-related waxing and waning of body weight, food consumption, and caloric
      efficiency, as well as associated changes in pancreatic islets and islet cells,
      and formation of liver tumors were assayed. While the hypothesis that these mice
      might serve as a tool for investigating hemochromatosis was not confirmed, the
      data did provide evidence that even the very low levels of ASP in pseudoagouti
      Avy/a mice affect the network of molecular/metabolic/physiological response
      pathways that comprises the yellow agouti obese phenome. We suggest that the
      combination of yellow agouti Avy/a, pseudoagouti Avy/a, and black a/a congenic
      mice provides a practical tool for applying a dose-response systems biology
      approach to understanding the dysregulatory influence of ectopic ASP on the
      molecular-physiological matrix of the organism.

PMID- 15982785
TI  - Mechanisms of enhanced taurine release under Ca2+ depletion.
AB  - The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the
      brain of mammals, as well as a key substance in the regulation of cell volumes.
      The effect of Ca(2+) on extracellular taurine concentrations is of special
      interest in the context of the regulatory mechanisms of taurine release. The aim
      of this study was to characterize the basal release of taurine in Ca(2+)-free
      medium using in vivo microdialysis of the striatum of anesthetized rats.
      Perfusion of Ca(2+)-free medium via a microdialysis probe evoked a sustained
      release of taurine (up to 180 % compared to the basal levels). The Ca(2+)
      chelator EGTA (1mM) potentiated Ca(2+) depletion-evoked taurine release. The
      substitution of CaCl(2) by choline chloride did not alter the observed effect.
      Ca(2+)-free solution did not significantly evoke release of taurine from tissue
      loaded with the competitive inhibitor of taurine transporter
      guanidinoethanesulfonate (1mM), suggesting that in Ca(2+) depletion taurine is
      released by the transporter operating in the outward direction. The volume
      sensitive chloride channel blocker diisothiocyanostilbene-2,2'-disulfonate (1mM)
      did not attenuate the taurine release evoked by Ca(2+) depletion. The non
      specific blocker of voltage-sensitive Ca(2+) channels NiCl(2) (0.65 mM) enhanced
      taurine release in the presence of Ca(2+). CdCl(2) (0.25 mM) had no effect under
      these conditions. However, both CdCl(2) and NiCl(2) attenuated the effect of
      Ca(2+)-free medium on the release of taurine. The data obtained imply the
      involvement of both decreased influx of Ca(2+) and increased non-specific influx
      of Na(+) through voltage-sensitive calcium channels in the regulation of
      transporter-mediated taurine release in Ca(2+) depletion.

PMID- 15982786
TI  - Similarities between CSF-brain extracellular transfer and neurofibrillary tangle
      invasion in Alzheimer's disease.
AB  - Using the in vivo enzyme protection-enzyme inhibition method, we visualized the
      distribution of the intraventricularly and cisternally (cisterna magna) injected
      ambenonium chloride (Am) bound reversibly to the extracellular
      acetylcholinesterase enzyme (AChE) in the rabbit brain in order to describe the
      extracellular flow pathways from the cerebrospinal fluid (CSF). We found that the
      distribution of Am-protected AChE (indicating the Am itself) is similar to
      tracers having no intracerebral binding sites. The topographical distribution
      after both ways of application indicates a preferential penetration of Am into
      the limbic structures of the cerebral hemispheres in a predictable topographic
      sequence starting from the corticoid areas, allo- and periallo cortices followed
      by the mesocortical regions and then, in a limited extent, to the isocortex. The
      lentiform nuclei and the central part of diencephalic halves are inaccessible to
      Am. The hierarchic order in the sequence of diffusion from the CSF into the
      hemispheric subpial regions and the distribution pattern of Am resemble the
      stereotypic topographic expansion pattern and the predominantly limbic
      distribution of neurofibrillary tangles (NFTs) in Alzheimer's disease and related
      conditions.

PMID- 15982787
TI  - Age differences in the neural systems supporting human allocentric spatial
      navigation.
AB  - Age-related declines in spatial navigation are well-known in human and non-human
      species. Studies in non-human species suggest that alteration in hippocampal and
      other neural circuitry may underlie behavioral deficits associated with aging but
      little is known about the neural mechanisms of human age-related decline in
      spatial navigation. The purpose of the present study was to examine age
      differences in functional brain activation during virtual environment navigation.
      Voxel-based analysis of activation patterns in young subjects identified
      activation in the hippocampus and parahippocampal gyrus, retrosplenial cortex,
      right and left lateral parietal cortex, medial parietal lobe and cerebellum. In
      comparison to younger subjects, elderly participants showed reduced activation in
      the hippocampus and parahippocampal gyrus, medial parietal lobe and retrosplenial
      cortex. Relative to younger participants elderly subjects showed increased
      activation in anterior cingulate gyrus and medial frontal lobe. These results
      provide evidence of age specific neural networks supporting spatial navigation
      and identify a putative neural substrate for age-related differences in spatial
      memory and navigational skill.

PMID- 15982788
TI  - An exploration into the most effective way to teach drug calculation skills to
      nursing students.
AB  - Drug calculations are an essential skill for nurses. Nurses need to be able to
      perform them accurately to calculate correct dosages of drugs to administer to
      patients. Incorrect calculations can cause drug errors and potential harm to
      patients (; ). For student nurses therefore learning how to calculate drug
      dosages is an important skill that they need to be taught during their nurse
      training. This paper describes an action research project undertaken to explore
      the most effective way of teaching drug calculations to a group if 2nd year
      diploma and degree pre registration nurses. The evaluation of this project has
      demonstrated that a three stage approach to drug calculation appears to be an
      effective teaching strategy. These stages involve addressing mathematical
      concepts, teaching drug calculation formulae and then practising these skills in
      a clinical setting.

PMID- 15982789
TI  - OSCEs--seven years on the bandwagon: the progress of an objective structured
      clinical evaluation programme.
AB  - The original purpose of Objective Structured Clinical Examination (OSCE), as
      first described in the medical literature [Harden, R.M., Stevenson, M., Downie,
      W.W., Wilson, G.M., 1975. Assessment of clinical competence using objective
      structured examination. British Medical Journal, 1, 447-451], provided a means of
      examining the skills acquisition of medical students. A review of the literature,
      since that time, provides the background to the development of OSCEs into pre
      registration nursing curricula, with the OSCE programme at the University of
      Salford presented here as a case study. The original student sample was a mixture
      of 150-250 adult, child and mental health students in each of seven cohorts over
      a period of four years. Each student undertook a 30-min formative, simulated
      patient, holistic care OSCE in their second year of the programme. Later
      developments included one remote workstation connected to and as part of the
      holistic patient care encounter. In subsequent curricula, the larger cohorts of
      around 250-300 students were accommodated in a formative rotational three
      workstation OSCE, based on clinical skills to be acquired prior to their first
      clinical placement. A summative patient-centred OSCE was undertaken in practice
      at a later date. The educational and practice value of OSCEs regarding their
      clinical content and context in nursing curricula now and in the future are
      explored, along with the practicalities of implementation.

PMID- 15982790
TI  - Analysis of efficacy of CVD 103-HgR live oral cholera vaccine against all-cause
      travellers' diarrhoea in a randomised, double-blind, placebo-controlled study.
AB  - Enterotoxigenic Escherichia coli (ETEC), which produces heat labile toxin (LT)
      and/or heat stable toxin (ST), is considered to be the most common known cause of
      travellers' diarrhoea (TD). Owing to the antigenic similarity between cholera
      toxin and LT, immunization with inactivated oral B-subunit/whole-cell cholera
      vaccine (BS-WC) offers short term (3 months) but significant (>67%) protection
      against TD caused by LT-related ETEC. Since it expresses the cholera toxin B
      (CTB) subunit, the live attenuated oral cholera vaccine strain CVD 103-HgR, may
      induce similar protection. A trial was performed to determine if CVD 103-HgR live
      oral cholera vaccine would provide a protective efficacy of at least 50% against
      TD. In addition, the protective efficacy of the vaccine against TD specifically
      due to LT-ETEC and LT/ST-ETEC was determined. Volunteers (n=134) travelling to
      Indonesia, India, Thailand or West-Africa were randomised to receive either a
      placebo (n=65) or the vaccine (n=69). In the placebo group, 46% reported an
      episode of diarrhoea, compared to 52% in the vaccine group. No significant group
      differences were found with regard to incidence, duration or severity of all
      caused TD or ETEC-associated TD. However, ETEC-associated TD occurred earlier in
      the placebo group (median 5 days), compared to the vaccine group (median 15
      days). In conclusion, CVD 103-HgR live oral cholera vaccine failed to provide a
      50% protection against TD. This study does not exclude that the vaccine may offer
      a short-lived protection against ETEC-associated TD. However, the power of the
      study was limited by the unexpected low incidence of LT-ETEC-associated diarrhoea
      (9% of all TD) compared to ST-associated TD (24% of all TD).

PMID- 15982791
TI  - Investigation of ansB and sspA derived promoters for multi- and single-copy
      antigen expression in attenuated Salmonella enterica var. typhimurium.
AB  - Five candidate promoters were examined to determine their utility in directing
      immunogenic levels of expression of the C fragment from tetanus toxin in
      attenuated S. enterica used as an oral vaccine in mice. Promoters derived from
      the genes encoding the stringent starvation protein (sspA) from E. coli and S.
      enterica, but not ansB derived promoters, expressed immunogenic levels of C
      fragment from multi-copy plasmids in attenuated S. enterica in vivo and,
      following oral immunization, induced high titre specific anti-tetanus toxoid
      serum antibodies. We also demonstrate that not only the choice of promoter,
      replicon and growth conditions but also how expression constructs are assembled
      in the chosen plasmid is critical for the successful development of plasmid-based
      antigen delivery systems using attenuated S. enterica. In addition, the S.
      enterica sspA promoter is able to elicit anti-tetanus toxoid antibodies in mice
      when the psspA-tetC expression cassette is integrated in single copy on the S.
      enterica chromosome.

PMID- 15982792
TI  - Chlamydia pneumoniae genome sequence analysis and identification of HLA-A2
      restricted CD8+ T cell epitopes recognized by infection-primed T cells.
AB  - In the present study, we performed in silico analysis of Chlamydia pneumoniae
      genome sequence to identify human HLA-A2-restricted T cell epitopes. Thirty-one
      Chlamydia-specific protein antigens were selected and peptides were derived
      thereof using an HLA-A2 epitope predictive algorithm. Firstly, we tested binding
      of 55 selected 9mer peptides to HLA-A2 in vitro. Next, infection of HLA-A2
      transgenic mice with C. pneumoniae elementary bodies and assessment of effector
      CD8+ T cells allowed us to identify which of the epitopes binding to HLA-A2 in
      vitro were recognized by C. pneumoniae infection-primed CD8+ T cells. Finally, we
      could confirm that CD8+ T cells in association with HLA-A2 recognized the most
      reactive peptides when the corresponding full-length genes were used to DNA
      immunize HLA-A2 transgenic mice. By using this approach, a novel HLA-A2
      restricted epitope in the outer membrane protein A (OmpA) of C. pneumoniae was
      identified, which proved to mediate specific lysis of peptide-loaded target
      cells.

PMID- 15982793
TI  - The effects of geology and the impact of seasonal correction factors on indoor
      radon levels: a case study approach.
AB  - Geology has been highlighted by a number of authors as a key factor in high
      indoor radon levels. In the light of this, this study examines the application of
      seasonal correction factors to indoor radon concentrations in the UK. This
      practice is based on an extensive database gathered by the National Radiological
      Protection Board over the years (small-scale surveys began in 1976 and continued
      with a larger scale survey in 1988) and reflects well known seasonal variations
      observed in indoor radon levels. However, due to the complexity of underlying
      geology (the UK arguably has the world's most complex solid and surficial geology
      over the shortest distances) and considerable variations in permeability of
      underlying materials it is clear that there are a significant number of
      occurrences where the application of a seasonal correction factor may give rise
      to over-estimated or under-estimated radon levels. Therefore, the practice of
      applying a seasonal correction should be one that is undertaken with caution, or
      not at all. This work is based on case studies taken from the Northamptonshire
      region and comparisons made to other permeable geologies in the UK.

PMID- 15982794
TI  - Very low levels of methylmercury induce cell death of cultured rat cerebellar
      neurons via calpain activation.
AB  - Methylmercury, an environmental neurotoxicant, induces the apoptotic death of
      cerebellar granule cells in vitro at a low concentration. To further understand
      the mechanism of cell death, we used a rat cerebellar granule cell culture system
      to investigate whether the calpain/cyclin-dependent kinase 5 (cdk5)/p35 cascade,
      an important cascade for neuronal apoptosis, is involved in the methylmercury
      induced death. A noteworthy finding was that the cerebellar granular cell death
      was increased at a very low concentration of methylmercury, 30 nM, which is lower
      than that previously reported. The high sensitivity to methylmercury indicates
      that this culture system is useful for studying methylmercury toxicity at very
      low concentrations. Using this system, we here found that the methylmercury
      induced death was inhibited by the calpain inhibitor II. Furthermore, it was
      shown that, in methylmercury-exposed cells, alpha-fodrin and tau, calpain
      substrates, were cleaved to the fragments that disappeared by treatment with the
      calpain inhibitor II. We next assayed and showed that the intracellular Ca(2+)
      concentration in cerebellar granule cells increased after methylmercury exposure
      in a time- and dose-dependent manner, significantly even at 30 nM. These results
      indicated that a very low concentration of methylmercury causes the intracellular
      Ca(2+) concentration to increase, activates calpain in the cells, and then
      induces cell death. We further found that the p35 protein was also processed to
      p25 that forms the cdk5-p25 complex, a hyperactive kinase for tau. However, an
      immunoblot using the anti-phosphorylated tau antibody showed that there was no
      increase of phosphorylated tau in methylmercury-exposed cells. These results
      suggested that methylmercury-induced cell death via calpain activation should not
      involve the stimulation of tau phosphorylation activity.

PMID- 15982795
TI  - The ability of fruit teas to remove the smear layer: an in vitro study of tubule
      patency.
AB  - OBJECTIVES: Fruit teas are know to have an erosive effect on enamel, but the
      effects on dentine are unknown. Lesions of dentine hypersensitivity have numerous
      patent dentinal tubules and the aim of this paper was to examine the ability of
      various fruit teas to remove the smear layer. METHODS: The erosive potential of a
      variety of fruit teas was assessed in the laboratory by measuring their pH and
      neutralisable acidity. Smeared dentine specimens were prepared from extracted
      teeth and the ability of each tea to remove the smear layer was assessed by
      measuring the diameter and area of the opened tubules and counting the number of
      patent tubules seen in a unit area using scanning electron microscopy. A 0.2%
      citric acid solution was used as a positive control. RESULTS: The pH of the fruit
      teas ranged from 2.98 to 3.95 and the neutralisable acidity ranged from 10.63 to
      33.0 ml of 0.1 M NaOH. All the fruit teas tested were able to remove the smear
      layer. The mean diameter of the tubules ranged from 0.61 to 1.14 microm and the
      mean area ranged from 0.31 to 1.03 microm2. The number of patent tubules per
      specimen ranged from 13 to 121. CONCLUSION: All the fruit teas tested were found
      to be highly acidic and able to remove the smear layer.

PMID- 15982796
TI  - Immune, endocrine and cardiovascular responses to controllable and uncontrollable
      acute stress.
AB  - This study, using a triadic-yoked design, clarified the effects of
      controllability of acute stress on responses of immune, cardiovascular (heart
      rate and blood pressure), and cortisol activities. Forty-three women in their
      follicular phase completed a mental arithmetic task as a stressor in which
      controllability was manipulated by correct or yoked-bogus feedback. The task
      decreased proportions of CD3+ T cells, CD4+ T cells, and CD19+ B cells, whereas
      it increased the numbers of white blood cells, lymphocytes, natural killer (NK)
      cells, and NK cell activity (NKCA). Our main hypothesis that greater immune and
      cardiovascular responses to the task would be obtained under the uncontrollable
      condition than under the controllable condition was not supported. However, the
      uncontrollable stress condition, but not the controllable situation, led to
      higher correlations between heart rate or blood pressure, and various immune
      parameters. On the other hand, parameters of heart rate variability reflecting
      sympathetic and parasympathetic activities showed significant correlations only
      with NKCA. These results suggest that immune responses were most directly
      associated with cardiovascular activities under the uncontrollable condition.

PMID- 15982797
TI  - Use of prostate-specific antigen (PSA) isoforms for the detection of prostate
      cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta
      analysis.
AB  - OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) for the detection
      of prostate cancer has poor specificity in men with PSA levels between 2 and 10
      ng/ml. It has been suggested that measurement of the ratio of free to total PSA
      (f/tPSA) or complexed PSA (cPSA) might offer an improvement. We performed a
      systematic review and meta-analysis to evaluate the diagnostic performance of
      these tests among men with PSA levels between 2 and 10 ng/ml. METHODS: Data on
      sensitivity and specificity were extracted from 66 eligible studies. Likelihood
      ratios and summary receiver operating characteristic curves were estimated and
      possible sources of heterogeneity between studies examined. RESULTS: Use of the
      f/tPSA or the cPSA test improved diagnostic performance among men with a total
      PSA (tPSA) of 2-4 or 4-10 ng/ml compared to tPSA alone. The diagnostic
      performance of the f/tPSA test was significantly higher in the tPSA range of 4-10
      ng/ml compared to a tPSA range of 2-4 ng/ml (p < 0.01); at a sensitivity of 95%,
      the specificity was 18% in the 4-10 ng/ml tPSA range and 6% in the 2-4 ng/ml tPSA
      range. Among studies that measured both isoforms, the diagnostic performance of
      the f/tPSA test and the cPSA was equivalent in both PSA ranges. CONCLUSIONS: The
      use of the f/tPSA or cPSA test among men with PSA levels between 2 and 10 ng/ml
      can reduce the number of unnecessary biopsies whilst maintaining a high cancer
      detection rate.

PMID- 15982799
TI  - EAU guidelines for the management of genitourinary tuberculosis.
AB  - Nearly one third of the world's population is estimated to be infected with
      Mycobacterium tuberculosis. Moreover, tuberculosis is the most common
      opportunistic infection in AIDS patients. Genitourinary tuberculosis is not very
      common but it is considered as a severe form of extra-pulmonary tuberculosis The
      diagnosis of genitourinary tuberculosis is made based on culture studies by
      isolation of the causative organism; however, biopsy material on conventional
      solid media may occasionally be required. Drug treatment is the first line
      therapy in genitourinary tuberculosis. Treatment regimens of 6 months are
      effective in most of the patients. Although chemotherapy is the mainstay of
      treatment, surgery in the form of ablation or reconstruction may be unavoidable.
      Both radical and reconstructive surgery should be carried out in the first 2
      months of intensive chemotherapy.

PMID- 15982798
TI  - Liposomal recombinant human superoxide dismutase for the treatment of Peyronie's
      disease: a randomized placebo-controlled double-blind prospective clinical study.
AB  - OBJECTIVE: To demonstrate the efficacy and safety of a topical gel containing
      liposomally encapsulated recombinant human Superoxide Dismutase (lrhSOD) in the
      treatment of painful Peyronie's Disease. The theoretical background is that
      lrhSOD, by scavenging of free oxygen radicals, might interrupt inflammatory
      cascades and thereby limit further disease progression. METHODS: In a placebo
      controlled randomized clinical trial, 39 patients with Peyronie's Disease and
      significant pain symptoms were treated with lrhSOD or placebo for a 4 week
      period. At this time, statistical evaluation of pain resolution was performed as
      primary study endpoint. Patients then were continued in a cross-over study design
      to ensure a total of 8 weeks of lrhSOD therapy for all study participants. Pain,
      plaque and curvature assessment was performed at study entry and every 4 weeks
      until week 12. RESULTS: LrhSOD treatment resulted in a statistically significant
      reduction of pain (p=0.017) compared to placebo already after 4 weeks. At week 12
      pain was significantly reduced in 89% of patients who all had received 8 weeks of
      lrhSOD therapy at that time. Response to other disease parameters was assessed at
      week 12: plaque size was reduced in 47% of patients, as was plaque consistence in
      38%. Penile curvature was improved at 5-30 degrees in 23% of patients. The
      expected spontaneous disease progression rate of up to 40%, as reported by
      several investigators, was significantly reduced to <10% under lrhSOD therapy,
      and patients satisfaction was high, also consequent to the lack of therapy
      related side effects observed in the present study. CONCLUSION: LrhSOD is an
      easily administrable, safe and effective local therapeutic for the painful phase
      of Peyronie's Disease.

PMID- 15982800
TI  - Markov chains: computing limit existence and approximations with DNA.
AB  - We present two algorithms to perform computations over Markov chains. The first
      one determines whether the sequence of powers of the transition matrix of a
      Markov chain converges or not to a limit matrix. If it does converge, the second
      algorithm enables us to estimate this limit. The combination of these algorithms
      allows the computation of a limit using DNA computing. In this sense, we have
      encoded the states and the transition probabilities using strands of DNA for
      generating paths of the Markov chain.

PMID- 15982801
TI  - DNA algorithm for an unbounded fan-in Boolean circuit.
AB  - In this paper, we present a new DNA-based evaluation algorithm for a Boolean
      circuit that employs standard bio-molecular techniques. The algorithm operates on
      an unbounded fan-in Boolean circuit consisting of AND and OR gates. The whole
      simulation of our algorithm is proposed in a single test tube in O(1) time
      complexity and is much easier to implement in the laboratory than previously
      described models. Furthermore, the algorithm allows for evaluating any number of
      Boolean circuits in parallel in a single test tube.

PMID- 15982802
TI  - Effects of patch temperature on spontaneous action potential train due to channel
      fluctuations: coherence resonance.
AB  - Based on the Hodgkin-Huxley (HH) model, the effects of patch temperature as a
      control parameter on the spontaneous action potentials for finite size of
      membrane patch are studied. With increasing patch temperature, it is found that
      the mean open rates of sodium and potassium channels of the HH neuron are
      decreased, and the mean duration of spikes of membrane potential is also
      decreased, which are qualitatively consistent with previous experimental results
      of single ion channel. Under moderate patch size, the mean interspike interval of
      membrane potential first decreases, reaches a minimum, and then increases with
      increasing patch temperature. It is shown that for both low and high
      temperatures, the channels fluctuation-induced spontaneous action potentials
      appear to be rather irregular, while for moderate patch temperature, relatively
      coherent oscillations observed. By defining a measure parameter beta, we show
      that there is a maximal region for the measure beta in the patch temperature and
      patch size parameter plane where the coherence resonance phenomena are very
      remarkable, and the characteristic correlation time of the output also confirm
      our result.

PMID- 15982803
TI  - Computational studies on conditions of the emergence of autopoietic protocells.
AB  - It has been pointed out that the acquisition of self-maintaining protocells was
      one of the most important evolutionary steps in the earliest stage of life.
      However, there remains little evidence to show what the components of the
      protocells were and how they were acquired. A theoretical study to investigate
      the possible process of the emergence of protocells is therefore required. In
      this paper, we present a computational model that demonstrates the emergence and
      evolution of self-maintaining and self-reproducing structures to analyze
      conditions under which precellular autocatalytic molecules could evolve into self
      reproducing protocells. We focused on the supply rates of molecular resources as
      environmental parameters and explored the pathways of evolution from molecular
      replication to cellular reproduction under various conditions. The results showed
      that the spontaneous organization of protocells from a random initial state takes
      place in a parameter region where the metabolism becomes difficult because of an
      insufficient supply of resources, but once cell structures are organized, they
      can survive in a wider range of environments. We investigated the evolution in
      temporally or spatially changing environments and found that the protocells can
      take over the precellular metabolic system after the transition. These results
      suggest a possible scenario for the evolution from precellular to cellular
      reproduction.

PMID- 15982804
TI  - Tissue MMP-2 and MMP-9 [corrected] are better prognostic factors than serum MMP
      2/TIMP-2--complex or TIMP-1 [corrected] in stage [corrected] I-III lung
      carcinoma.
AB  - Matrix metalloproteinases (MMPs) are involved in tumor growth and spreading.
      Here, we investigated the tumor immunoreactive protein of MMP-2, MMP-9 and TIMP-1
      as well as the levels of circulating total TIMP-1 and MMP-2/TIMP-2-complex as
      prognostic factors in lung cancer patients. The material included 59 patients, 30
      with a squamous cell carcinoma, 21 with an adenocarcinoma and eight with other
      histology. Circulating antigens were measured by ELISA assay and the protein
      expression in primary tumors was analyzed by streptavidin-biotin
      immunohistochemical staining using specific monoclonal antibodies. The strong
      positivity for MMP-2 or MMP-9 in tumor predicted poor prognosis. The 5-year
      survival rates were 83 or 85% in patients negative for MMP-2 or MMP-9,
      respectively. Only 17% of the patients with a tumor highly positive for MMP-2 and
      43% of those with a high positivity for MMP-9 survived at that time (Cox
      regression P=0.042 for MMP-2 and log rank P=0.046 for MMP-9). On the contrary,
      strong tissue positivity for TIMP-1 demonstrated a tendency for a favorable
      survival, although the difference did not reach statistical significance. In
      patients with a squamous cell carcinoma Stage I, low serum TIMP-1 (<or=300 ng/ml)
      also predicted unfavorable survival (log rank P=0.033). Further in subgroup of
      patients treated by lobectomy (n=29), the high levels of circulating MMP-2/TIMP-2
      complex (>or=300 ng/ml) associated with an increased survival rate, the 5-year
      survival being 81 versus 34% (log rank P=0.069) in patients with high or low
      serum levels for MMP-2/TIMP-2-complex, respectively. Tissue MMP-2 correlated to
      high expression of MMP-9 immunoreactive protein (P=0.003), but the serum levels
      of MMP-2/TIMP-2-complex or TIMP-1 did not correlate to the immunostaining of the
      corresponding tumors. We conclude that in lung carcinoma the best prognostic
      value is achieved by using immunohistochemistry for MMP-2 and MMP-9. In early
      disease, however, serum TIMP-1 or MMP-2/TIMP-2-complex could offer some further
      prognostic value.

PMID- 15982806
TI  - Effect of arsenic trioxide on multidrug resistant hepatocellular carcinoma cells.
AB  - Our previous study showed that arsenic trioxide (As2O3) was effective in
      inhibiting the growth of human hepatocellular carcinoma (HepG2) cells via
      induction of apoptosis. In the present study, we examined the effect of As2O3 on
      multidrug resistant human hepatocellular carcinoma (R-HepG2) cells which are
      characterized with overexpression of mdr1 gene and P-glycoprotein. The anti
      proliferation of R-HepG2 by As2O3 was examined by MTT assay. For the induction of
      apoptosis, DNA fragmentation and Annexin V-PI staining were performed after
      treatment with arsenic trioxide. To study the effect of arsenic trioxide on P
      glycoprotein, Western analysis probing anti-P-glycoprotein antibody was used to
      monitor the change of its expression. Results showed that As2O3 was effective in
      inhibiting the cell proliferation of R-HepG2 cells in a dose- and time-dependent
      manner via induction of apoptosis without affecting the cell cycle. The
      sensitivity of R-HepG2 cells toward As2O3 was found to be similar to that of the
      parental HepG2 cells. The Western analysis showed that As2O3 was probably not the
      substrate to be bound and extruded by P-glycoprotein in R-HepG2 cells because it
      could not maintain the cellular P-glycoprotein expression.

PMID- 15982805
TI  - A thioredoxin reductase inhibitor induces growth inhibition and apoptosis in five
      cultured human carcinoma cell lines.
AB  - Human thioredoxin reductase (TrxR) system is associated with cancer cell growth
      and anti-apoptosis process. Effects of 1, 2-[bis (1,2-Benzisoselenazolone-3 (2H) 
      ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on A549, HeLa,
      Bel-7402, BGC823 and KB cell lines. After treated with BBSKE, a good linear
      correlation coefficient (r>or=0.989) between TrxR activity and cell viability
      exists in each cell line together with cell growth/proliferation inhibition and
      apoptosis through Bcl-2/Bax and Caspase-3 pathways. These results suggest that
      there exists some relationship between TrxR inactivation and growth/proliferation
      inhibition or apoptosis in the investigated cell lines.

PMID- 15982807
TI  - Permeation of Telone EC through protective gloves.
AB  - Telone is a potent fumigant that is based on the chlorinated unsaturated
      hydrocarbon, 1,3-dichloropropene (1,3-DCP). It is often applied without dilution
      and so poses severe inhalation and air pollution threats. Urinary metabolites of
      1,3-DCP have been detected after Telone skin exposure, so that preventing dermal
      exposure is also important. The objective of the study was to assess if nitrile
      and multi-layer ("laminated") gloves provide adequate protection against Telone
      EC formulation. To accomplish this, disposable (Safeskin) and chemically
      resistant (Sol-Vex) nitrile and laminated (Barrier mark and Silver Shield) glove
      materials were challenged by Telone EC with hexane liquid collection in an ASTM
      type I-PTC-600 permeation cell. Analyses of cis- and trans-1,3-DCP in the
      collection fluid at specified times were performed on a moderately polar
      capillary column by gas chromatography-electron capture detection. Telone EC
      caused microholes in both nitrile materials, though the chemically protective
      material was degraded slower than the disposable nitrile. The laminated gloves
      offered limited protection. Silver Shield protected best because 1.5-2.3 mg 1,3
      DCP permeated by 8 h relative to 2.5-7.6 mg for Barrier, implying about 2.5 times
      more protection for 8 h. Even for Silver Shield, the extent of protection was
      inadequate as illustrated by a risk assessment of the skin exposure situation.
      The normalized breakthrough times for both types of laminated gloves varied
      between 27 and 60 min. It is recommended that Viton gloves still be worn for
      protection.

PMID- 15982808
TI  - Decolorization and mineralization of a phthalocyanine dye C.I. Direct Blue 199
      using UV/H2O2 process.
AB  - In this study, the successful decolorization and mineralization of phthalocyanine
      dye (C.I. Direct Blue 199, DB 199) by an advanced oxidation process (AOP),
      UV/H2O2, were observed while the experimental variables such as hydrogen peroxide
      dosage, UV dosage, initial dye concentration and pH were evaluated. The operating
      conditions for 90% decolorization of C.I. DB 199 and 74% removal of total organic
      carbon (TOC) were obtained for initial dye concentration of 20 mgl(-1), hydrogen
      peroxide dosage of 116.32 mM, UV dosage of 560 W and pH of 8.9 in 30 min. The
      pseudo-first order rate constant is a linear function of reverse of initial dye
      concentration. They linearly increased by incrementing UV dosage, yet were non
      linear enhancement by increasing the hydrogen peroxide concentration. A higher
      pseudo-first order rate constant about 0.15 min(-1) was observed while hydrogen
      peroxide concentration within 5.82-116.32 mM. Moreover, the decolorization of
      C.I. DB 199 was observed to be more difficult than that of an azo dye, C.I. Acid
      Black 1, under the same operating conditions.

PMID- 15982809
TI  - Pretreatment with antiserum against dynorphin, substance P, or cholecystokinin
      enhances the morphine-produced anti-allodynia in the sciatic nerve ligated mice.
AB  - It is generally accepted that neuropathic pain is resistant to amelioration by
      morphine in clinical studies and insensitivity to intrathecal (i.t.) administered
      morphine in experimental models of neuropathic pain has been demonstrated. This
      study is to determine if endogenous dynorphin, substance P or cholecystokinin is
      involved in the lack of anti-allodynia of morphine in a partial sciatic nerve
      ligation (PSL) model of CD-1 mice. Mice exhibited tactile allodynia in the
      ipsilateral hind paw 1 day after PSL, and reached its maximal allodynic effect at
      2 days and remained allodynic for 7 days. Morphine (3.0 nmol) given i.t. did not
      alter the tactile allodynic threshold in ipsilateral paw of mice pretreated i.t.
      with normal rabbit serum 2 days after PSL. However, the same dose of morphine
      (3.0 nmol) given i.t. reduced markedly allodynia in mice pretreated for 2h with
      antiserum against dynorphin A(1-17) (200 microg); the morphine-produced anti
      allodynia developed slowly, reached its peak effect at 30 min and returned to an
      allodynic state in 60 min. Similarly, i.t. injection of morphine reduced the
      allodynia in PSL mice pretreated with antiserum against substance P (10 microg)
      or cholecystokinin (200 microg) for 2h. Intrathecal pretreatment with antiserum
      against dynorphin A(1-17), substance P or cholecystokinin for 2h injected alone
      did not affect the baseline mechanical tactile threshold in ipsilateral paw 2
      days after PSL. The results indicate that endogenous dynorphin A(1-17), substance
      P and cholecystokinin are involved in PSL-induced neuropathic allodynia to
      attenuate the anti-allodynic effect of morphine.

PMID- 15982810
TI  - Dissociation between "where" and "how" judgements of one's own motor performance
      in a video-controlled reaching task.
AB  - The aim of the present study is to show that the sensorimotor system makes a
      differential use of visual and internal (proprioception and efferent copy)
      signals when evaluating either the spatial or the dynamical components of our own
      motor response carried out under a remote visual feedback. Subjects were required
      to monitor target-directed pointings from the images furnished by a video camera
      overhanging the workspace. By rotating the camera, the orientation of the
      movement perceived on the screen was either changed by 45 degrees (visual bias)
      or maintained in conformity with the actual trajectory (0 degrees ). In either
      condition, after completing twenty pointings, participants had to evaluate their
      visuomotor performance in two non visual testing: They were both asked to reach
      the target in a single movement (evaluation of "how to reach the target"), and to
      evaluate the mapping of the spatial layout where they acted (evaluations of
      "where the starting position was and, what movement direction was"). Results
      revealed that though motor performance in the 45 degrees conditions was adapted
      to the visuomotor conflict, participants' evaluation of the spatial aspect of the
      performance was affected by the biased visual information. A different pattern
      was revealed for the evaluation of "how" the target was reached which was not
      affected by the visual bias. Thus, it is suggested that segregated processing of
      visual and kinesthetic information occurs depending upon the dimension of the
      performance that is judged. Visual information prevails when identifying the
      spatial context of a motor act whereas proprioception and/or efferent copy
      related signals are privileged when evaluating the dynamical component of the
      response.

PMID- 15982811
TI  - Primum non nocere--first do no harm.

PMID- 15982812
TI  - Use of a novel thermal operant behavioral assay for characterization of orofacial
      pain sensitivity.
AB  - Orofacial pain has been well-characterized clinically, but evaluation of
      orofacial pain in animals has not kept pace. The objective of this study was to
      describe behavioral responses to facial thermal stimulation and inflammation
      with/without an analgesic using a novel operant paradigm. Animals were trained to
      voluntarily place their face against a stimulus thermode (37.7-57.2 degrees C)
      providing access to positive reinforcement. These contingencies present a
      conflict between positive reward and tolerance for nociceptive stimulation.
      Inflammation was induced and morphine was provided as an analgesic in a subset of
      animals. Six outcome measures were determined: reward intake, reward licking
      contacts, stimulus facial contacts, facial contact duration, ratio of
      reward/stimulus contacts, and ratio of facial contact duration/event. Animals
      displayed aversive behaviors to the higher temperatures, denoted by a significant
      decrease in reward intake, total facial contact duration, and reward licking
      events. The number of facial contacts increased with increasing temperature,
      replacing long drinking bouts with more frequent short drinks, as reflected by a
      low ratio of facial contact duration/event. The number of reward licking/facial
      contact events was significantly decreased as the thermal stimulus intensity
      increased, providing another pain index derived from this operant method. These
      outcomes were significantly affected in the direction of increased nociception
      following inflammation, and these indices of hyperalgesia were reversed with
      morphine administration. These data reflect an orofacial pain behavior profile
      that was based on an animal's responses in an operant escape paradigm. This
      technique allows evaluation of nociceptive processing and modulation throughout
      the neuraxis.

PMID- 15982813
TI  - Dose-dependent effects of morphine on experimentally induced cutaneous pain in
      healthy volunteers.
AB  - This study examines the dose dependent analgesic effects of two doses of morphine
      and a single dose of alfentanil on experimentally induced cutaneous pain. In 16
      healthy volunteers pain was induced by a skin burn injury and by continuous
      electrical skin stimulation. Mechanical pain thresholds (PT, von Frey filament),
      area of secondary hyperalgesia (SH) and 'wind-up like pain' upon repetitive
      stimulation (40-g load, 3Hz, 30s) were assessed. Analgesic effects on these pain
      parameters were tested at steady-state IV infusions of morphine, 50% (plasma
      concentration 15ng/ml) and 100% (plasma concentration 30ng/ml) of maximal
      tolerable dose to be given to healthy volunteers, and with an effective dose of
      alfentanil (plasma concentration 70ng/ml). All effects were compared to active
      placebo, midazolam infusion (20microg/kg for 10min). Alfentanil significantly
      diminished the SH area in the burn injury model as well as in the electrical pain
      model. Additionally, alfentanil increased PT several fold in both models. The
      high dose of morphine showed a similar analgesic response pattern as alfentanil
      even though the effects were only statistically significant in the electrical
      pain model. The low dose of morphine as well as placebo did not affect these pain
      parameters. 'Wind-up like pain' was not influenced by any of the given drugs. In
      conclusion, the present study clearly indicates dose dependent effects of
      morphine on experimentally induced cutaneous pain. The high dose of morphine
      (30ng/ml) was approximately equianalgesic to the administered alfentanil dose
      (70ng/ml).

PMID- 15982814
TI  - Sex differences in musculoskeletal pain in older adults.
AB  - Little is known about sex differences in musculoskeletal pain in older persons.
      There were 682 women and 380 men aged 72 years and older who participated in the
      22nd biennial exam of the Framingham Study (1992-1993). Participants were asked
      to identify pain locations on a homunculus showing all regions of the body. Pain
      was categorized according to number of regions, with the most disseminated pain
      classified as widespread pain (back pain and upper and lower extremity pain with
      bilaterality). Among the women, 63% reported pain in one or more regions,
      compared to 52% of men. Widespread pain was more prevalent among women than men
      (15 versus 5%, respectively). In both men and women, pain was associated with
      fair or poor self-rated health, history of back pain before age 65, and
      disability. Factors associated with pain only in women included body mass index,
      systolic blood pressure, and depressive symptoms. In men but not women, pain was
      associated with polyarticular radiographic osteoarthritis. In conclusion,
      musculoskeletal pain was more prevalent and more widespread in older women than
      older men. Men and women differ in the factors associated with musculoskeletal
      pain in older ages. Further research is needed to understand sex differences in
      musculoskeletal pain the older population.

PMID- 15982815
TI  - Is morphine-3-glucuronide of therapeutic relevance?

PMID- 15982816
TI  - Functional connectivity and pain: how effectively connected is your brain?

PMID- 15982817
TI  - Comparative actions of the opioid analgesics morphine, methadone and codeine in
      rat models of peripheral and central neuropathic pain.
AB  - Controversy persists in relation to the analgesic efficacy of opioids in
      neuropathic pain. In the present study the effects of acute, subcutaneous
      administration of the mu-opioid receptor agonists morphine, methadone and codeine
      were examined in rat models of peripheral and central neuropathic pain. In the
      spared nerve injury (SNI) and chronic constriction injury (CCI) models of
      peripheral neuropathic pain, both morphine (6mg/kg) and methadone (3mg/kg)
      attenuated mechanical allodynia, mechanical hyperalgesia and cold allodynia for
      up to 1.5h post-injection (P<0.05); codeine (30mg/kg) minimally alleviated
      mechanical hypersensitivity in SNI, but not CCI rats. When administered to rats
      with photochemically-induced spinal cord injury (SCI), morphine (2 and 6mg/kg)
      and methadone (0.5-3mg/kg) robustly attenuated mechanical and cold allodynia for
      at least 2h post-injection (P<0.05). Codeine (10 and 30mg/kg) also attenuated
      mechanical and cold allodynia in this model for at least 3h after injection. The
      magnitude of opioid-mediated antinociception was similar between SNI, SCI and non
      injured rats as measured in the tail flick test. At antinociceptive doses, no
      motor impairment as determined by the rotarod test was observed. The therapeutic
      window (based on antiallodynia versus ataxia) obtained for codeine, was vastly
      superior to that obtained with morphine or methadone in SNI and SCI rats.
      Furthermore, the therapeutic window for codeine in SCI rats was 4-fold greater
      than in SNI rats. Our results further support the efficacy of mu-opioid receptor
      agonists in alleviating signs of neuropathic pain in animal models of peripheral
      and especially central nerve injury.

PMID- 15982818
TI  - Evaluation of the infectivity of Trichinella papuae and Trichinella zimbabwensis
      for equatorial freshwater fishes.
AB  - The discovery of Trichinella species infecting poikilotherm vertebrates has
      opened new possibilities in the epidemiology of this parasite group. The aim of
      the present work was to investigate the infectivity of the two non-encapsulated
      species of Trichinella infecting both mammals and reptiles, Trichinella papuae
      and Trichinella zimbabwensis, for equatorial freshwater carnivore fishes. To this
      end, two species of piranhas, four Serrasalmus nattereri and four Serrasalmus
      rhombeus, were each inoculated per os with the two species of Trichinella larvae.
      Six days post infection (p.i.), one fish of each species inoculated with one of
      the two species of Trichinella was sacrificed. The intestines and celomatic
      cavities were searched for worms using dissection microscopy, and the presence of
      muscle larvae was evaluated by artificial digestion. The other 4 inoculated fish
      were sacrificed 60 days p.i. and similarly searched for the presence of worms. No
      larva or adult worms were detected in any organ or tissue at 6 or 60 days p.i.
      The lack of infectivity of T. papuae and T. zimbabwensis for fish suggests that
      the entozoic habitat of this animal does not represent a suitable environment for
      these two Trichinella species. More importantly, these data indicate that
      freshwater fishes, one of the food resources for crocodiles, caimans and
      alligators, are unlikely to play a role in the epidemiology of the known species
      of the genus Trichinella.

PMID- 15982819
TI  - Giardia in shellfish-farming areas: detection in mussels, river water and waste
      waters.
AB  - Giardia cyst contamination of mussels (Mytilus galloprovincialis), raw and
      treated waste waters and water from rivers that flow into four Galician estuaries
      (NW Spain), where bivalve molluscs are cultured for human consumption, was
      studied. The high prevalence of contamination in mussels (41.8%, n=184), raw
      waste water (90.9%, n=11), treated waste water (87.5%, n=16) and in samples of
      river water (85.7%, n=7), with cyst counts of 9.8-1800.0, 7.0-2541.0 and 1.0-29.3
      cysts l(-1), respectively, illustrate the wide distribution of this
      enteropathogen in the environment and the potential risk to public health
      associated with the consumption of raw or undercooking bivalves and use of these
      estuaries for recreational purposes.

PMID- 15982820
TI  - Comparison of two antigens for demonstration of Trichinella spp. antibodies in
      blood and muscle fluid of foxes, pigs and wild boars.
AB  - For the surveillance of trichinellosis, the digestion method is reliable but also
      labour intensive. The serological methods for the detection of Trichinella
      specific antibodies using ELISA offer a sensitive and relatively specific
      alternative. For serological studies, sera or plasma from blood samples are the
      most common source of antibodies, but although the concentration of antibodies is
      approximately 10-fold lower, muscle fluid can be a good alternative particularly
      for testing of wildlife samples. In the present study, an indirect ELISA
      technique was evaluated on both sera and muscle fluids from experimentally
      infected foxes, pigs, and wild boars using both excretory/secretory (E/S)
      antigens and a synthetic glycan antigen, beta-tyvelose. Although the synthetic
      antigen appears to be less sensitive than the E/S antigens, Trichinella-specific
      IgG antibodies were detected in both serum samples and muscle fluid samples from
      pigs, wild boars and foxes infected at levels which would be important for food
      safety or represent a significant reservoir for further transmission.

PMID- 15982821
TI  - Molecular phylogenetic studies on an unnamed bovine Babesia sp. based on small
      subunit ribosomal RNA gene sequences.
AB  - The 18S small subunit ribosomal RNA (18S rRNA) gene of an unnamed Babesia species
      (designated B. U sp.) was sequenced and analyzed in an attempt to distinguish it
      from other Babesia species in China. The target DNA segment was amplified by
      polymerase chain reaction (PCR). The PCR product was ligated to the pGEM-T Easy
      vector for sequencing. It was found that the length of the 18S rRNA gene of all
      B. U sp. Kashi 1 and B. U sp. Kashi 2 was 1699 bp and 1689 bp. Two phylogenetic
      trees were, respectively, inferred based on 18S rRNA sequence of the Chinese
      bovine Babesia isolates and all of Babesia species available in GenBank. The
      first tree showed that B. U sp. was situated in the branch between B. major Yili
      and B. bovis Shannxian, and the second tree revealed that B. U sp. was confined
      to the same group as B. caballi. The percent identity of B. U sp. with other
      Chinese Babesia species was between 74.2 and 91.8, while the percent identity
      between two B. U sp. isolates was 99.7. These results demonstrated that this B. U
      sp. is different from other Babesia species, but that two B. U sp. isolates
      obtained with nymphal and adultal Hyalomma anatolicum anatolicum tick belong to
      the same species.

PMID- 15982822
TI  - Progress in analytical imaging of the cell by dynamic secondary ion mass
      spectrometry (SIMS microscopy).
AB  - This paper reviews the most recent methodological advances in the field of
      biological imaging using dynamic secondary ion mass spectrometry (SIMS). After a
      short reminder of the basic principle of SIMS imaging, the latest high-resolution
      dynamic SIMS equipment is briefly described. This new ion nanoprobe (CAMECA
      NanoSIMS 50) has a lateral resolution of less than 50 nm with primary Cs+ ion,
      the ability to detect simultaneously 5 different ions from the same micro-volume
      and a very good transmission even at high mass resolution (60% at M/DeltaM=5000).
      Basic considerations related to sample preparation, mass resolution and primary
      ion implantation are given. The decisive capability of this new instrument, and
      more generally of high-resolution dynamic SIMS imaging in biology, are
      illustrated with the most recent examples of utilization.

PMID- 15982823
TI  - Real-time and automatic sorting of multi-neuronal activity for sub-millisecond
      interactions in vivo.
AB  - Recent in vitro electrophysiological studies have revealed that neighboring
      interneurons interact with each other in a sub-millisecond time range via gap
      junctions and that individual dendritic compartments generate local excitation
      spikes and back-propagated spikes within a single-neuron. However, most in vivo
      electrophysiological studies using behaving animals only focus on activity rates
      of single-neurons and/or large neuronal populations without considering the
      potential role of such sub-millisecond interactions among neurons. This neglect
      is due to the limitation of ordinary in vivo multi-neuronal recording and spike
      sorting techniques applied to behaving animals. Though independent component
      analysis (ICA) is a powerful method to overcome certain limitations, ICA has a
      serious problem in that the number of single-electrodes (microwires) must be more
      than the number of single-neurons to be recorded. Our recently-developed method
      has solved this limitation of ICA, but a few problems have remained: the
      computational load is heavy, the method can be used only for off-line, not real
      time, processing, and the electrode-neuron drift problem remains unsolved. In
      this paper, solving all these problems, we introduce a novel system consisting of
      automatic and real-time spike sorting with ICA in combination with a newly
      developed multi-electrode, dodecatrode. The system has the potential to answer
      some important neurobiological questions that have not been explored in in vivo
      electrophysiological experiments: how sub-millisecond interactions between
      closely neighboring single-neurons act in freely behaving animals. The system
      promises to be a bridge connecting electrophysiological studies in vitro and in
      vivo.

PMID- 15982824
TI  - Ethnic similarities and differences in reasons for smoking.
AB  - We examined reasons for smoking among Black and White smokers. We hypothesized
      that Blacks would be more likely than Whites to cite tension reduction and less
      likely to cite weight control as a reason for smoking. Black (n = 100) and White
      (n = 100) female smokers completed the Reasons for Smoking Scale and the Smoking
      Situations Questionnaire. Regardless of treatment status, Blacks and Whites
      differed in their reasons for smoking [F(6,191) = 2.24; p < .05]. Blacks, as
      compared to Whites, less strongly endorsed weight concern as a reason for smoking
      [F(1,198) = 6.10; p < .05]. Results failed to reveal differences in tension
      reduction, stimulation, handling, relaxation, addiction, and habit as a function
      of ethnicity. Results suggest that Blacks and Whites exhibit more similarity than
      difference in their reasons for smoking.

PMID- 15982825
TI  - The effect of abstinence on cigarette consumption upon the resumption of smoking.
AB  - To study the impact of abstinence on the number of cigarettes smoked per day upon
      the resumption of smoking, adult current smokers completed retrospective surveys
      in two studies. The consumption rate demonstrated at the resumption of smoking
      fell with progressively longer abstinence periods out to 6 months, showing little
      further reduction even after years of abstinence. Subjects in Study 1 (n=848)
      resumed smoking at 34% of their lifetime peak rate of consumption, accelerating
      to 58% at 2 weeks, to 64% at 1 month, and to 68% at 6 months. Subjects in Study 2
      (n=803) resumed smoking at 48% of their pre-quit peak rate of consumption,
      accelerating to 69% at 1 week, to 78% at 2 weeks, and to 88% at 6 months. The
      trajectory of consumption with the resumption of smoking differs from that in
      novice smokers, suggesting that some impact of nicotine persists during
      abstinence. The shapes of the observed trajectories suggest that more than one
      process may be at work. Prospective studies are needed to confirm these findings.

PMID- 15982826
TI  - Transition to injection and sharing of needles/syringes: potential for HIV
      transmission among heroin users in Chengdu, China.
AB  - This cross-sectional survey interviewed heroin injectors admitted in three
      detoxification centres from August 2003 to June 2004 in Chengdu City, China.
      Logistic regression and survival analysis were performed to identify factors
      associated with sharing of needles/syringes and time from initiation of heroin to
      adoption of injection, respectively. Out of 266 subjects studied, 206 (77.44%)
      were males, 103 (38.72%) never shared injecting materials, 113 (42.48%) were non
      Chengdu residents and 9 (3.38%) belonged to ethnic minorities. Those with short
      history of heroin injection (P<0.05) and those belonged to ethnic minorities
      (P<0.05) were more likely to share injecting materials. Only age, ethnicity and
      duration of heroin use were associated with time to first injection. Median time
      to injection was 6 months for those who used heroin for the duration up to 1 year
      and 21 months for those who used heroin for 2-5 years. The study suggests that
      there is early initiation of injection and sharing of injecting materials is high
      among heroin users, a major risk for HIV transmission. Ethnic minorities have
      been identified to be the most risky group, which needs further attention.

PMID- 15982827
TI  - Alcohol use in New York after the terrorist attacks: a study of the effects of
      psychological trauma on drinking behavior.
AB  - Research has suggested that exposure to psychological trauma is associated with
      increased abuse of psychoactive substances, particularly alcohol. To assess this,
      we analyzed alcohol consumption, binge drinking, and alcohol dependence among a
      random sample of 1681 New York City adults 1 year and 2 years after the September
      11 attacks. In multivariate models controlling for demographic factors, other
      stressor exposures, social psychological resources, and history of anti-social
      behavior, we found that greater exposure to the World Trade Center disaster
      (WTCD) was associated with greater alcohol consumption at 1 year and 2 years
      after this event. In addition, our analyses also indicated that exposure to the
      WTCD was associated with binge drinking at 1 year after but not 2 years after
      this event. Alcohol dependence, assessed as present in either year 1 or year 2,
      also was positively associated with greater WTCD exposures. Posttraumatic stress
      disorder was not associated with alcohol use, once WTCD exposure and other
      covariates were controlled. Our study suggests that exposure to psychological
      trauma may be associated with increases in problem drinking long after exposure
      and deserves further investigation.

PMID- 15982828
TI  - The relationship between impaired decision-making, sensation seeking and
      readiness to change in cigarette smokers.
AB  - OBJECTIVE: The study investigated whether impaired decision-making as measured by
      the Gambling Task and Sensation Seeking, on one hand, and nicotine-dependence and
      readiness to change, on the other hand, show mutual influences in cigarette
      smokers. METHODS: Cigarette smokers were classified as dependent or non-dependent
      smokers. Assessment included stages of change (RCQ), decisional balance (DBS),
      Sensation Seeking Scale Form-V (SSS-V), and performance on the Gambling Task
      (GT). RESULTS: With the exception of a significant higher score in the SSS-V
      subscale Experience Seeking in dependent smokers, correlations between nicotine
      dependence and cognitive features were not significant. The directions of the non
      significant differences were not consistent. No significant relationship was
      found between the SSS-V and the GT, on one hand, and the readiness to change
      smoking behaviour, on the other hand. CONCLUSIONS: The results of the present
      study suggest that impaired performance on the GT and high scores in Sensation
      Seeking do not play an important role in nicotine-dependence and readiness to
      change smoking behaviour or vice versa.

PMID- 15982829
TI  - Smoking in pregnancy: the role of the transtheoretical model and the mother's
      attachment to the fetus.
AB  - This study investigated whether pregnant smokers demonstrated cognitive and
      behavioural patterns hypothesised to underpin the different stages of change
      (SOC) and whether fetal attachment varied according to this process. A cross
      sectional design with women categorised by SOC was used and the sample was
      recruited from hospital maternity services in the U. K at their booking clinics
      with a mean gestation of 14 weeks. Experiential and behavioural processes
      together with self-efficacy and attachment to the fetus were measured in 637
      women. As predicted by the transthoretical model experiential processes were used
      mostly by women in contemplation and preparation; behavioural processes mostly by
      women in preparation and action. However, self-efficacy remained constant between
      pre-contemplation, contemplation and preparation, but women in action showed
      significantly higher levels. Women in preparation were significantly more
      attached to the fetus than women in pre-contemplation and never smokers. The
      relevance of the transtheoretical model with pregnant smokers is supported.
      Foetal attachment may be differentially associated with different SOC in smoking
      cessation and yield potential for the development of new interventions.

PMID- 15982830
TI  - Hypnosis and meditation: similar experiential changes and shared brain
      mechanisms.

PMID- 15982831
TI  - Combining transfusion of stem/progenitor cells into the peripheral circulation
      with localized transplantation in situ at the site of tissue/organ damage: a
      possible strategy to optimize the efficacy of stem cell transplantation therapy.
AB  - Several studies have demonstrated the efficacy of localized in situ
      transplantation of stem/progenitor cells for tissue/organ regeneration. However,
      the possible limitations of such an approach have largely been overlooked. This
      is contrary to the intrinsic physiological process of tissue/organ regeneration
      in vivo, which is thought to involve the mobilization of stem/progenitor cells
      resident within the tissue/organ itself, as well as from ectopic sites, in
      particular the bone marrow. Signaling pathways and other molecular processes
      within stem/progenitor cells transplanted in situ may not be primed to achieve
      optimal tissue/organ regeneration, and may even be confused by the sudden rapid
      transition in the cellular microenvironment encountered during transplantation.
      To overcome these putative limitations, a possible strategy may be to combine
      transfusion of stem/progenitor cells into the peripheral circulation with
      localized transplantation in situ at the site of tissue/organ damage. This could
      better replicate the natural physiological process of tissue/organ repair in
      vivo. Possible synergistic interactions between the transplanted stem/progenitor
      cells in situ with migratory transfused cells from the peripheral circulation may
      further enhance tissue/organ regeneration. The transfused stem/progenitor cells
      may be induced to home in on a damaged tissue/organ, via the controlled release
      of specific cytokines or chemokines (i.e., SDF-1) emanating from that particular
      tissue/organ. There are a number of possible ways to achieve this. For example,
      the transplanted cells may be delivered on tissue-engineered scaffolds that are
      designed for the controlled release of specific homing factors such as SDF-1.
      Another alternative may be to stimulate or genetically modulate the transplanted
      cells to copiously secrete homing factors such as SDF-1, to encourage the
      migration and homing of transfused cells within the peripheral circulation. At
      the same time, it may also be advantageous to pre-stimulate the transfused cells
      to strongly express surface receptors specific to homing factors such as SDF-1,
      in particular CXCR-4. More rigorous investigations should be carried out on the
      possible strategy of combining in situ transplantation of stem/progenitor cells
      with transfusion into the peripheral circulation, together with induced homing of
      the transfused cells to the site of organ/tissue damage. This may possibly result
      in better efficacy for some, but not all models of tissue/organ regeneration.

PMID- 15982832
TI  - Buddlin, a new compound from Buddleja asiatica.
AB  - A new compound, named buddlin (1), was isolated from the whole plant of Buddleja
      asiatica. Its structure was elucidated from spectral evidence.

PMID- 15982833
TI  - Assessment of diagnostics and antimicrobial susceptibility testing of Brachyspira
      species using a ring test.
AB  - There is no ring test for quality assessment available in Europe for diagnostics
      and antimicrobial susceptibility testing of the fastidious, anaerobic bacteria of
      the genus Brachyspira. Therefore, an international ring test for Brachyspira spp.
      was performed once a year during 2002-2004. Two sets of coded samples were
      prepared and distributed on each occasion. One set comprised six swabs dipped in
      pig faeces spiked with Brachyspira spp. intended for diagnostics. The other set
      comprised two pure strains intended only for susceptibility testing. All methods
      used were in-house methods. The species used were Brachyspira hyodysenteriae,
      Brachyspira pilosicoli, Brachyspira innocens, Brachyspira murdochii and
      Brachyspira intermedia. In most cases, the correct Brachyspira spp. were
      detected. However, the results showed that Brachyspira spp. could be difficult to
      identify, especially if two Brachyspira spp. were mixed or if the concentration
      of Brachyspira in faeces was low. Additionally, some laboratories reported
      Brachyspira growth in control samples that were not seeded with any spirochaetes.
      The lowest detection level was 10(2) bacteria/ml faeces for both B.
      hyodysenteriae and B. pilosicoli. The susceptibility tests performed showed that
      disc diffusion was not recommendable for Brachyspira spp. Extended antimicrobial
      dilution series gave most congruent results. The diversity of the results
      highlights the importance of ring tests for a high quality of diagnostics and
      antimicrobial susceptibility tests for Brachyspira spp. This is the first ring
      test described for Brachyspira spp.

PMID- 15982834
TI  - Investigation of the Booroola (FecB) and Inverdale (FecX(I)) mutations in 21
      prolific breeds and strains of sheep sampled in 13 countries.
AB  - Twenty-one of the world's prolific sheep breeds and strains were tested for the
      presence of the FecB mutation of BMPR1B and the FecX(I) mutation of BMP15. The
      breeds studied were Romanov (2 strains), Finn (2 strains), East Friesian,
      Teeswater, Blueface Leicester, Hu, Han, D'Man, Chios, Mountain Sheep (three
      breeds), German Whiteheaded Mutton, Lleyn, Loa, Galician, Barbados Blackbelly
      (pure and crossbred) and St. Croix. The FecB mutation was found in two breeds, Hu
      and Han from China, but not in any of the other breeds. The 12 Hu sheep sampled
      were all homozygous carriers of FecB (FecB(B)/FecB(B)) whereas the sample of 12
      Han sheep included all three genotypes (FecB(B)/FecB(B), FecB(B)/FecB+,
      FecB+/FecB+) at frequencies of 0.33, 0.58 and 0.08, respectively. There was no
      evidence of FecX(I) in any of the breeds sampled.

PMID- 15982835
TI  - GnRH in non-hypothalamic reproductive tissues.
AB  - Gonadotropin releasing hormone (GnRH) is a hypothalamic neuronal secretory
      decapeptide that plays a pivotal role in mammalian reproduction. GnRH and its
      analogues are used extensively in the treatment of hormone dependent diseases and
      assisted reproductive technology. Fourteen structural variants and three
      different forms of GnRH, named as hypothalamic GnRH or GnRH-I, mid brain GnRH or
      GnRH-II and GnRH-III across various species of protochordates and vertebrates
      have been recognised. The hormone acts by binding to cell surface transmembrane G
      protein coupled receptors (GPCRs) and activates Gq/11 subfamily of G proteins.
      Although hypothalamus and pituitary are the principal source and target sites for
      GnRH, several reports have recently suggested extra-hypothalamic GnRH and GnRH
      receptors in various reproductive tissues such as ovaries, placenta, endometrium,
      oviducts, testes, prostrate, and mammary glands. GnRH-II appears to be
      predominantly expressed in extra pituitary reproductive tissues where it produces
      its effect by PLC, PKA2, PLD, and AC cell signalling pathways. In these tissues,
      GnRH is considered to act by autocrine or paracrine manner and regulate ovarian
      steroidogenesis by having stimulatory as well as inhibitory effect on the
      production of steroid hormones and apoptosis in ovarian follicle and corpus
      luteum. In male gonads, GnRH has been shown to cause a direct stimulatory effect
      on basal steroidogenesis and an inhibitory effect on gonadotropin-stimulated
      androgen biosynthesis. Recent studies have shown that GnRH is more abundantly
      present in ovarian, endometrial and prostrate carcinomas. The presence of type-II
      GnRH receptors in reproductive tissues (e.g. gonads, prostrate, endometrium,
      oviduct, placenta, and mammary glands) suggests existence of distinct role(s) for
      type-II GnRH molecule in these tissues. The existence of different GnRH forms
      indicates the presence of distinctive cognate receptors types in vertebrates and
      is a productive area of research and may contribute to the development of new
      generation of GnRH analogues with highly selective and controlled action on
      different reproductive tissues and the target-specific GnRH analogues could be
      developed.

PMID- 15982836
TI  - The pituitary effects of GnRH.
AB  - Advances in our understanding of the complexity of GnRH actions at the pituitary
      and the various mechanisms involved in mediating differential LH and FSH
      biosynthesis and secretion at the gonadotrope, are continually emerging. In this
      review, we summarise recent studies pertaining to GnRH and GnRH receptor
      phylogeny, the divergent signalling and trafficking pathways initiated and
      utilised by GnRH and its receptor, and the pathways that mediate gonadotropin
      secretion from the gonadotrope.

PMID- 15982837
TI  - Hysterectomy prevalence and cardiovascular disease risk factors in American
      Indian women.
AB  - OBJECTIVES: We investigated hysterectomy prevalence and associated demographic
      and reproductive factors among American Indian women. The association between
      hysterectomy and cardiovascular disease (CVD) risk factors was also examined.
      METHODS: Data were from 2689 American Indian women who participated in the first
      examination of the Strong Heart Study from 1989 to 1992. Odds ratios were
      estimated for factors related to hysterectomy adjusting for other covariates. The
      association between hysterectomy and CVD risk factors was examined among 1726
      eligible women using analysis of covariance. RESULTS: Hysterectomy prevalence
      ranged from 24% to 34% across differing age groups and the percent with
      oophorectomy among those with a hysterectomy ranged from 43% to 63%. Geographic
      area, more prior pregnancy losses, more education, and less speaking of the
      native language were associated with increased hysterectomy prevalence. After
      adjustment for age, the women who had a hysterectomy with intact ovaries had
      higher total cholesterol and low-density lipoprotein cholesterol levels than
      those with a natural menopause. CONCLUSIONS: American Indian women have
      comparable hysterectomy prevalence as non-Hispanic white women. Education and
      native language speaking related to hysterectomy in this population. Hysterectomy
      alone may relate to unfavorable changes of lipid profile.

PMID- 15982838
TI  - Liriopis tuber inhibit OVA-induced airway inflammation and bronchial
      hyperresponsiveness in murine model of asthma.
AB  - Liriope platyphylla is one of the well-known herb used in oriental medicine for
      treatment asthma and bronchial and lung inflammation. Anti-asthmatic effects of
      Liriope platyphylla in the development of OVA-induced airway inflammation and
      murine asthma model have not been fully investigated in vivo. Asthma is a chronic
      inflammatory disease of the mucosa and is associated with excess production of
      Th2 cytokines and eosinophil accumulation in lung. To clarify the anti
      inflammatory and anti-asthmatic effects of Liriope platyphylla, we examined the
      influence of liriopis tuber (LRT) on the development of pulmonary eosinophilic
      inflammation in murine model of asthma. Our results have shown that LRT were
      demonstrated on the accumulation of eosinophills into airways, with reduction of
      eosinophil, total lung leukocytes numbers by reduction IL-5, IL-13, IL-4 and IgE
      levels in the BALF and serum. Moreover, LRT decreased eosinophil CCR3 expression
      and CD11b expression in lung cells. These results indicate that LRT has a deep
      inhibitory effects on airway inflammation and hyperresponsiveness in murine model
      of asthma and play an crucial role as a immunomodulator which possess anti
      inflammatory and anti-asthmatic property by modulating the relationship between
      Th1/Th2 cytokine imbalance.

PMID- 15982839
TI  - Non-diagnosed pheochromocytoma as a cause of sudden death in a 49-year-old man: a
      case report with medico-legal implications.
AB  - Pheochromocytomas are known to be rare causes of sudden death. A 49-year-old man
      with a medical history of arterial hypertension and diabetes mellitus complained
      about nausea and malaise in the morning. During the day his condition
      deteriorated. He went to the emergency department, where he was given intravenous
      drugs against nausea and was sent home. On the way back, his condition
      deteriorated dramatically so that his wife drove back to the emergency room,
      where he collapsed and sustained cardiac arrest; resuscitation efforts were
      unsuccessful. Autopsy revealed a large tumour of the left adrenal gland. The
      strong suspicion of pheochromocytoma was confirmed by histology,
      immunohistochemistry and biochemical investigations. An acute hypertensive
      crisis, caused by the hitherto unknown pheochromocytoma was ascertained as the
      cause of death. The morphological findings are presented, the difficulty to
      diagnose pheochromocytoma and the medico-legal implications are discussed.

PMID- 15982840
TI  - Criminal burning.
AB  - We report a study of 40 burnt bodies on which an autopsy was carried out at the
      Institut de Medecine Legale in Lyon (28 men/12 women, average age = 41 years,
      minimum age = 3 years, maximum age = 86 years). Criminal deaths (31%) represented
      the second cause of death after accidents (52%), and before suicide (16%).
      Criminal burning seemed mainly to be means of covering up homicide, whereas
      criminal immolation was rarer. The particular characteristics of each of these
      situations have been highlighted (tying or poisoning in criminal immolation). We
      deemed it essential to make X-rays, to look for injuries due to trauma and to
      carry out systematic toxicological analyses in a victim of burning.

PMID- 15982841
TI  - Development of a heptaplex PCR system to analyse X-chromosome STR loci from five
      Italian population samples. A collaborative study.
AB  - Many X-chromosome short tandem repeats (X-STRs) have been validated for forensic
      use even if further studies are needed on allele frequencies and mutation rates
      to evaluate the extent of polymorphism in different populations and to establish
      reference databases useful for forensic applications and for anthropological
      studies. A single multiplex reaction of seven X-STRs, which includes the DXS6789,
      HUMARA, DXS10011, DXS7423, HPRTB, DXS6807, DXS101 loci, is presented and their
      allele frequency distribution in a large population sample including 556 subjects
      (268 females and 288 males) analysed by five forensic laboratories of Central and
      Northern Italy is shown. Our results demonstrate the feasibility of a single
      amplification/detection reaction involving seven markers of the X chromosome,
      which can be fruitfully used in complex kinship analysis.

PMID- 15982842
TI  - [Bacillus licheniformis: an unusual cause of erysipelosis].
AB  - The authors report a case of a cutaneous infection due to Bacillus licheniformis.
      It occurred after a wound due to a wicker splinter. The bacteriological
      identification was easy thanks to the very typical aspects of culture. First
      intention antibiotherapy given for bacterial dermo-hypodermatitis may be
      ineffective because Bacillus licheniformis secretes a biofilm and is frequently
      resistant to Beta-lactams.

PMID- 15982843
TI  - [A study on antiretroviral treatment compliance in Casablanca (Morocco)].
AB  - OBJECTIVE: Compliance in HIV infection treatment is a major stake to give
      worldwide access to antiretroviral (ARV) treatment and especially in Africa. In
      September 2003, we undertook a study on compliance among HIV positive patients
      under antiretroviral treatment. These patients were included in a therapeutic
      educational program in the infectious diseases department of the Casablanca
      University Hospital (Morocco). The main objective of the study was to assess
      obstacles to compliance and to find possible solutions. DESIGN: A transversal
      investigation was made, based on questionnaires for patients under ARV treatment,
      chosen consecutively. The physician's and the educator's opinion on patient
      compliance was collected. RESULTS: Patients were between 21 and 65 years of age.
      Ninety-two patients were questioned and 89 analyzed. Treatment duration lasted
      from 2 to 67 months. Compliance according to educators was good (>90%) for 78
      patients. The main obstacles for a good compliance were difficulty to respect
      administration schedule and the long distance between home and hospital, or the
      presence of adverse effects and other diseases. CONCLUSIONS: The role of the
      therapeutic educational program in improving compliance was largely highlighted.

PMID- 15982845
TI  - [Shoulder arthritis due to Haemophilus aphrophilus].
AB  - We report a case of shoulder arthritis due to Haemophilus aphrophilus. The
      patient, a 56 year-old woman, was immunocompetent. She presented with a septic
      arthritis of the left shoulder without portal of entry. A synovial fluid sample
      was cultured and positive for a gram-negative bacillus after 8 days. It was
      identified as Haemophilus aphrophilus, in the HACCEK group, by PCR ARN 16S. We
      did not find any associated endocarditis. The patient recovered. As far as we
      know, this is only the 5th reported case of arthritis due to this microorganism.

PMID- 15982846
TI  - [Bacteremia and pneumonia due to Yersinia enterocolitica serotype O:3 in an
      immunocompetent patient].
AB  - The authors report a rare case of Yersinia enterocolitica O:3 pneumonia in an
      immunocompetent 70-year old man. There was no evidence of acute gastrointestinal
      disease. Diagnosis was confirmed by blood cultures. He responded with resolution
      of the infection after 21 days of therapy with a third-generation cephalosporin
      then by cotrimoxazole. Only 15 cases have been reported so far. Most of the
      patients were immunocompromised. This is the first case in France.

PMID- 15982847
TI  - [Reactive arthritis due to Clostridium difficile].
AB  - Extracolonic manifestations of Clostridium difficile infections have rarely been
      reported as a cause of reactive arthritis. We report the case of a monoarticular
      arthritis following pseudomembranous colitis. A 45 year-old man was admitted for
      fever and monoarthritis of the left knee, 8 days after the onset of a C.
      difficile enterocolitis associated with urethritis. Samples obtained from the
      knee, urine, and blood cultures remained sterile. Bone scintigraphy revealed a
      left knee and forefoot hyperfixations. The association of arthritis and
      urethritis led us to the diagnosis of Fiessinger-Leroy-Reiter syndrome.
      Antibiotics for arthritis were ineffective and stopped, but they were continued
      for colitis. NSAIDs were prescribed and clinical manifestations disappeared
      within 24 hours, the patient resumed walking after 48 hours. Four months later
      there was no relapse and no sequela.

PMID- 15982848
TI  - [Treatment of febrile neutropenia episodes in children, with a piperacillin
      tazobactam and netilmicin combination].
AB  - OBJECTIVES: The authors had for aim to assess the effectiveness and toxicity of a
      piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding
      using glycopeptide, in children with febrile neutropenic episodes induced by
      chemotherapy. METHODS: A retrospective study was made, including children treated
      for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by
      a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours
      after the beginning of antibiotic therapy, a glycopeptide could be added. The
      responses to the treatment were defined as follows: 1) total success (no fever or
      documented infection) at 48 hours and at 72 hours following the beginning of
      treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic
      change); 3) failure (persistent infectious signs 48 hours after the introduction
      of glycopeptide). RESULTS: Sixty-nine episodes were assessable, corresponding to
      41 patients, treated for a solid tumour (29), an acute leukaemia in remission
      (11), or a metabolic disease (1). The febrile episodes were divided into fever of
      unknown origin (71%), microbiologically documented fever (12%), and clinically
      documented fever (17%). No death occurred, no toxicity was reported. With this
      antibiotic therapy, total success at 72 hours was observed in 72% in case of
      fever of unknown origin and 45% in case of documented infections. The success
      rate reached 84% when a glycopeptide was added (30% of the cases). CONCLUSION:
      The piperacillin-tazobactam-netilmicin combination is very effective and well
      tolerated in probabilistic treatment of febrile neutropenia induced by
      chemotherapy, but does not allow to decreasing the frequency of glycopeptide
      administration.

PMID- 15982849
TI  - Adaptation and performance of an immuno-PCR assay for the quantification of
      Aviscumine in patient plasma samples.
AB  - An immuno-polymerase chain reaction (IPCR) assay is used to evaluate the kinetic
      behaviour of the novel anti-cancer drug Aviscumine in plasma samples taken from
      41 patients during a 3-year clinical trial. The ultrasensitive IPCR assay
      employed the amplification of a detection-antibody linked marker-DNA and an
      internal competitor DNA for standardization, thus enabling the detection of the
      antigen in concentrations far below the detection limit of conventional enzyme
      linked immuno-sorbent assay (ELISA). The quantification of Aviscumine was carried
      out using external calibration curves obtained from individual patient plasma
      samples, collected previous to the administration of Aviscumine, which were
      spiked with known amounts of the reference substance Aviscumine. Additional
      controls were measured containing standardized human serum spiked with Aviscumine
      to assure the continuous general reproducibility of the assay as well as to
      estimate differences between individual patients. Average recovery was found to
      be 95+/-19% and the average deviation in precision of the assay was determined to
      be 9+/-5%. Data for the quantification of Aviscumine were obtained from all
      patient samples investigated with the exception of a single patient. The
      collected data provided the basis for the valid routine quantification of patient
      samples for the calculation of the pharmacokinetic behaviour of Aviscumine in
      patient plasma.

PMID- 15982850
TI  - Intrauterine growth restriction-etiology and consequences: what do we know about
      the human situation and experimental animal models?
AB  - Embryonic and fetal growth depend on genetic and environmental factors, and the
      process is the result of the interaction between these factors. About 7-9% of
      live-born infants have a birth weight below normal (below the 10th percentile).
      The rate and extent of intrauterine growth restriction (IUGR) varies by ethnicity
      and socio-economic status. Some of the suspected causes of IUGR are as follows.
      (1) Maternal factors such as inadequate or severe malnutrition, chronic maternal
      diseases, birth order, multiple births, and parental genetic factors. (2)
      Placental pathology, mainly placental vascular damage that may lead to placental
      insufficiency. This is often found in maternal diseases such as pre-eclampsia,
      and Thrombophilia. (3) Intrauterine infections and specific fetal syndromes,
      including chromosomal aberrations. (4) Non-classified causes such as adolescent's
      pregnancy, maternal smoking and alcohol drinking, living at high altitudes.
      Several existing animal models for IUGR, including uterine artery ligation or
      gene knock out models, although insightful of potential mechanism(s) underlying
      intrauterine growth restriction, are limited in that they do not reflect human
      causality. As the ultimate goal is prevention, we seem still to be distant from
      achieving this goal.

PMID- 15982851
TI  - Oral misoprostol and uterine rupture in the first trimester of pregnancy: a case
      report.
AB  - We are reporting the case of a woman with 8 weeks of amenorrhea who orally
      received a single dose of misoprostol 400 microg at midnight for ripening of
      cervix before uterine evacuation of an intrauterine gestational sac containing a
      single fetus (6.3 weeks of gestation) without cardiac activity. The patient had
      severe abdominal pain an hour later. Her blood pressure was 70/40 mmHg and her
      abdomen was slightly distended with direct and rebound tenderness. A transvaginal
      ultrasonography showed a 3-cm depth of a free fluid collection in the
      rectouterine pouch. Her hemoglobin and hematocrit levels were of 6.5 g/dL and
      18.4%, respectively. A rupture of 1.5 cm at the left uterine horn with a
      protruding gestational sac was identified by laparoscopy. The gestational sac was
      removed and hemoperitoneal collection were successfully drained. The site of
      uterine rupture was primarily sutured and postoperative course was satisfactory.
      In summary, misoprostol administered in the first trimester of pregnancy may
      produce uterine rupture.

PMID- 15982852
TI  - Reactive oxygen species generated by hematopoietic cytokines play roles in
      activation of receptor-mediated signaling and in cell cycle progression.
AB  - Hematopoietic cytokines, including interleukin (IL)-3 and erythropoietin (Epo),
      regulate hematopoiesis by stimulating their receptors coupled with the Jak2
      tyrosine kinase to induce receptor tyrosine phosphorylation and activate mainly
      the STAT5, PI3K/Akt, and Ras/MEK/ERK signaling pathways. Here we demonstrate that
      IL-3 or Epo induces a rapid and transient (peaking at 30 min) as well as late
      progressive increase in reactive oxygen species (ROS) in a hematopoietic
      progenitor model cell line, 32Dcl3, and its subclone expressing the Epo receptor
      (EpoR), 32D/EpoR-Wt. The cytokine-induced ROS generation was not affected in
      32Dcl3 cells depleted of mitochondrial DNA. The antioxidant N-acetyl-L-cysteine
      (NAC) inhibited IL-3-induced tyrosine phosphorylation of Jak2, IL-3 receptor
      betac subunit (IL-3Rbetac), and STAT5 as well as activation-specific
      phosphorylation of Akt, MEK, and ERK, while treatment of cells with H2O2
      activated these signaling events. NAC also inhibited the EpoR-induced
      transphosphorylation of IL-3Rbetac. Moreover, NAC treatment reduced the
      expression levels of c-Myc, Cyclin D2, and Cyclin E, and induced expression of
      p27, thus inhibiting the G1 to S phase transition of cells cultured with IL-3.
      Further studies have shown that the degradation of c-Myc was facilitated or
      inhibited by treatment of cells with NAC or H2O2, respectively. These data
      indicate that the rapid generation of ROS by cytokine stimulation, which is at
      least partly independent of mitochondria, may play a role in activation of Jak2
      and the STAT5, PI3K/Akt, and Ras/MEK/ERK signaling pathways as well as in
      transactivation of cytokine receptors. The cytokine-induced ROS generation was
      also implicated in G1 to S progression, possibly through stabilization of c-Myc
      and induction of G1 phase Cyclin expression leading to suppression of p27.

PMID- 15982853
TI  - Autocrine, paracrine and juxtacrine signaling by EGFR ligands.
AB  - Receptor and cytoplasmic protein tyrosine kinases play prominent roles in the
      control of a range of cellular processes during embryonic development and in the
      regulation of many metabolic and physiological processes in a variety of tissues
      and organs. The epidermal growth factor receptor (EGFR) is a well-known and
      versatile signal transducer that has been highly conserved during evolution. It
      functions in a wide range of cellular processes, including cell fate
      determination, proliferation, cell migration and apoptosis. The number of ligands
      that can activate the EGF receptor has increased during evolution. These ligands
      are synthesized as membrane-anchored precursor forms that are later shed by
      metalloproteinase-dependent cleavage to generate soluble ligands. In certain
      circumstances the membrane anchored isoforms as well as soluble growth factors
      may also act as biologically active ligands; therefore depending on the
      circumstances these ligands may induce juxtacrine, autocrine, paracrine and/or
      endocrine signaling. In this review, we discuss the different ways that EGFR
      ligands can activate the receptor and the possible biological implications.

PMID- 15982854
TI  - Influence of arthroscopically observed fibrous adhesions before and after joint
      irrigation on clinical outcome in patients with chronic closed lock of the
      temporomandibular joint.
AB  - The aim of this study was to investigate the changes in the state of
      arthroscopically observed fibrous adhesions (FA) after visually guided irrigation
      (VGIR) and the influence of FA on clinical outcome in patients with chronic
      closed lock of the temporomandibular joint (TMJ). Forty-eight TMJs of 48 patients
      with unilateral chronic closed lock were enrolled in this study. All 48 joints
      underwent VGIR twice. After the first VGIR (immediately before the second VGIR),
      clinical outcome was assessed as regards maximal interincisal opening (MIO) and
      self-evaluated TMJ pain (VAS). Thirty patients were symptom-free (good outcome
      group) and the remaining 18 patients had symptoms (poor outcome group). In each
      group, the changes of the MIO, VAS and severity of FA (FA score) after the first
      VGIR were studied. The influence of FA score in the first and second VGIR on
      clinical outcome was analyzed by logistic regression analysis. There was no joint
      with disappearance or reduction of FA after the first VGIR. In both groups, MIO
      and VAS were significantly improved after the first VGIR even though the state of
      FA became significantly worse. The multivariate logistic regression analysis
      showed that the risk of poor outcome for FA scores in the first and second VGIR
      were 0.89-times (95% CI: 0.33-2.40, P=0.82) and 1.76-times (95% CI: 0.54-5.73,
      P=0.35), respectively. The dose-response relationships between FA scores in the
      first or second VGIR were not significant. In conclusion, our results indicate
      that the presence of FA or a postoperative worsening of FA (including
      postoperative new FA formation) seems not to affect the clinical outcome as
      regards MIO and VAS in patients with chronic closed lock of the TMJ.

PMID- 15982855
TI  - A study of osteoclast-related cytokines in mandibular invasion by squamous cell
      carcinoma.
AB  - The purpose of this study was to analyze the mechanism of bone invasion in
      carcinoma of the mandibular gingiva. We investigated 38 specimens of lower
      gingival carcinoma and histopathologically classified them into an invasion group
      (23 cases) and a non-invasion group (15 cases) on the basis of light microscopy
      evidence. These specimens were examined using immunohistochemical techniques
      involving antibodies of parathyroid hormone-related protein (PTHrP), tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, -1beta, -6, -11, -18 and
      transforming growth factor (TGF)-beta. The invasion group showed a high level of
      expression of PTHrP, TNF-alpha, IL-6 and IL-11 positive cells (P<0.01 versus non
      invasion group). The difference in the levels of expression of IL-1alpha, -1beta,
      -18 and TGF-beta positive cells was not significant between these two groups. Our
      results suggest that various cancer-derived cytokines, such as PTHrP, TNF-alpha,
      IL-6 and IL-11, play an important role in the mechanism of bone invasion
      associated with lower gingival squamous cell carcinoma.

PMID- 15982856
TI  - What does the PANSS mean?
AB  - OBJECTIVE: Despite the frequent use of the Positive and Negative Syndrome Scale
      (PANSS) for rating the symptoms of schizophrenia, the clinical meaning of its
      total score and of the cut-offs that are used to define treatment response (e.g.
      at least 20% or 50% reduction of the baseline score) are as yet unclear. We
      therefore compared the PANSS with simultaneous ratings of Clinical Global
      Impressions (CGI). METHOD: PANSS and CGI ratings at baseline (n = 4091), and
      after one, two, four and six weeks of treatment taken from a pooled database of
      seven pivotal, multi-center antipsychotic drug trials on olanzapine or
      amisulpride in patients with exacerbations of schizophrenia were compared using
      equipercentile linking. RESULTS: Being considered "mildly ill" according to the
      CGI approximately corresponded to a PANSS total score of 58, "moderately ill" to
      a PANSS of 75, "markedly ill" to a PANSS of 95 and severely ill to a PANSS of
      116. To be "minimally improved" according to the CGI score was associated with a
      mean percentage PANSS reduction of 19%, 23%, 26% and 28% at weeks 1, 2, 4 and 6,
      respectively. The corresponding figures for a CGI rating "much improved" were
      40%, 45%, 51% and 53%. CONCLUSIONS: The results provide a better framework for
      understanding the clinical meaning of the PANSS total score in drug trials of
      schizophrenia patients with acute exacerbations. Such studies may ideally use at
      least a 50% reduction from baseline cut-off to define response rather than lower
      thresholds. In treatment resistant populations, however, even a small improvement
      can be important, so that a 25% cut-off might be appropriate.

PMID- 15982857
TI  - Effect of several sterilisation techniques on homogeneous self assembled
      monolayers.
AB  - Understanding how cells sense their environment and are able to regulate their
      metabolism is of great importance for the success of biomaterials implantation.
      Self assembled monolayers (SAMs) are in use nowadays to model the surface of such
      materials. They permit the control of different surface parameters (like
      chemistry, surface energy and topography) enabling to get a greater insight in
      cells behaviour when interacting with surfaces and thus, in the future, to
      enhance surface properties of biomaterials. As sterilisation is the compulsory
      step for in vitro and in vivo assays with living biological materials, it is
      important to know how SAMs react under sterilisation techniques in use on
      biomaterials. In this work, the effect of three types of sterilisation
      techniques: gamma-irradiation, mostly used on biomaterials, dry heat and steam
      autoclaving, have been investigated on NH2 and CH3 terminated SAMs. Gamma
      irradiation destructs drastically the NH2 and partially the CH3 monolayers by
      producing oxidative compounds (COOH, C=O, C-OH). The main product induced by
      gamma-irradiation on NH2 monolayers is carboxylic acid, whereas CH3 shows an
      important increase in the amount of alcoholic groups. This difference in
      deterioration is assumed to be due to the higher stability of the CH3 monolayer.
      Steam autoclaving to a lesser extent gives the same results on NH2 monolayers.
      Dry heat seems to be the most reliable technique, which can be used on such
      surfaces as it removes physically adsorbed organic contaminants without affecting
      the integrity of the surface.

PMID- 15982858
TI  - The pharmacokinetics of perindoprilat in normal volunteers and patients:
      influence of age and disease state.
AB  - The purpose of the present report was to develop a pharmacokinetic model for
      perindoprilat based on three phase I studies including administration of oral and
      intravenous perindopril and administration of intravenous perindoprilat. The
      model was further refined using additional data collected from four phase II
      clinical trials including elderly volunteers and patients with hypertension,
      renal failure and heart failure. A two compartment pharmacokinetic model based on
      unbound concentration, in which perindoprilat bound to a single saturable binding
      site was used to analyze the intravenous data, whereas a one compartment model,
      also with saturable binding, was used for the oral data. The kinetics of
      perindoprilat were dose dependent with the apparent volume of distribution (V/F)
      varying from 920 L at a dose of 3.1 mg of perindoprilat to 470 L at a dose of
      12.3 mg, in normal volunteers. Apparent unbound clearance (CLu/F) ranged from 59
      to 110 L h(-1), showing no systematic trend with dose or from single to multiple
      dosing. Unbound clearance was strongly related to creatinine clearance in the
      patient studies and there was also a weak relationship between volume of
      distribution and creatinine clearance. Unbound clearance was also found to
      decrease with age. The binding parameters of the model were consistent with a
      single binding site to a protein having the characteristics of angiotensin
      converting enzyme (ACE).

PMID- 15982859
TI  - Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with
      a pharmacophoric conjugated diene.
AB  - Sesquiterpene acids are natural products that, in contrast with the thoroughly
      studied sesquiterpene lactones, have received little pharmacological attention. A
      good source of this class of compounds is Inula viscosa (Asteraceae), a plant
      with documented anti-inflammatory effects. The present paper gives the results of
      our investigations on the biochemical mechanisms involved in the anti
      inflammatory activity of one such compound, dehydrocostic acid. The most salient
      findings were that in vitro dehydrocostic acid inhibits leukotriene B(4)
      production (IC(50)=22 microM), elastase activity (IC(50)=43 microM) and bee venom
      phospholipase A(2) activity (IC(50)=17 microM). Furthermore, this sesquiterpenoid
      was effective on some models of acute edema induced by PLA(2) and 12-O
      tetradecanoylphorbol 13-acetate (TPA) Comparison of these data with that known
      for ilicic acid firmly suggests that the presence of a semiplanar ring A is
      essential for an improved inhibitory activity on inflammatory mediators.

PMID- 15982860
TI  - [Laparoscopic surgery in children].
AB  - In the last two decades, laparoscopy surgery has been progressively adopted to
      children. Cardiorespiratory changes induced have been understood and controlled.
      Abdominal and urological surgery have widely benefited from this technique.
      Immediate postoperative period is simpler. The risk of small bowel obstruction by
      bands and adhesions is limited. Nevertheless, laparoscopy is not indicated for
      all pathologies. In neonatal surgery, more studies are necessary. Maybe the
      future is robotic surgery.

PMID- 15982861
TI  - Matrix Gla protein C-terminal region binds to vitronectin. Co-localization
      suggests binding occurs during tissue development.
AB  - Matrix Gla protein (MGP) regulates calcification in cartilage and arteries. MGP
      synthesis during embryonic development and its binding and regulation of growth
      factors and morphogens of the TGF-beta/BMP superfamily suggests that it has
      additional functions. Assay by far-western gel overlays and gel filtration shift
      shows MGP binds vitronectin. Binding is saturable and consistent with a single
      class of binding sites. MGP binds to vitronectin but not collagen, fibromodulin,
      heparin, osteocalcin, chondroitin sulfate, laminin, ovalbumin or albumin. We have
      identified a vitronectin binding site within a 17-amino acid peptide 61-77 near
      the carboxyl-terminus that corresponds to a naturally occurring MGP C-terminus.
      MGP and the 61-77 MGP peptide also binds to fibronectin. MGP and vitronectin are
      focally co-localized in embryonic tissues. Co-localization in vivo suggests that
      the MGP and vitronectin interactions may modify cell-matrix interactions.
      Alternatively, vitronectin-bound MGP may have altered function for modulating
      BMP2 or TGF-beta activity. The current study demonstrates that MGP has a novel
      binding activity for vitronectin, an extracellular protein that promotes cell
      matrix interactions and regulates coagulation.

PMID- 15982863
TI  - Anti-inflammatory pathways as a host evasion mechanism for pathogens.
AB  - Lipoxins play a key role in controlling potent pro-inflammatory responses
      triggered by infection with pathogens, such as Toxoplasma gondii and
      Mycobacterium tuberculosis. In order to contain microbial dissemination, infected
      hosts must mount a powerful immune response to prevent mortality. The onset of
      the chronic phase of infection is characterized by continuous cell-mediated
      immunity. Such potent responses are kept under tight control by a class of anti
      inflammatory eicosanoids, the lipoxins. Here, we review such immune-containment
      strategies from the host's perspective, to keep pro-inflammatory responses under
      control during chronic disease, as well as from the perspective of the pathogen,
      which pirates the host's lipoxygenase machinery to its own advantage as a
      probable immune-escape mechanism.

PMID- 15982862
TI  - GATA-4 binds to an upstream element of the human alpha2(I) collagen gene (COL1A2)
      and inhibits transcription in fibroblasts.
AB  - Chromatin analyses have identified two DNase I hypersensitive sites (HS1 and HS2)
      at comparable distances (-130 bp and -2.3 kb) from the transcription start site
      of the human and mouse alpha2I collagen gene. Whereas the DNA region encompassing
      HS1 has been extensively characterized using protein binding and functional
      assays, nothing is yet known about the contribution of the HS2 sequence to
      alpha2I collagen gene transcription. Here we report that the HS2 sequence of the
      human alpha2I collagen (COL1A2) gene is a binding site for a transcriptional
      repressor in fibroblasts. DNase I footprinting identified a single site of
      nuclease protection around HS2, which corresponds to a sequence potentially
      capable of forming a 13 bp long hairpin structure with a 4 bp interruption in the
      middle. Gel mobility shift assays revealed that two GATA consensus sequences
      embedded within the hairpin are specifically bound by GATA-4 in fibroblasts. They
      also showed that formation of the HS2 protein complex requires the integrity of
      the whole hairpin sequence. Transient transfections of luciferase reporter gene
      constructs in fibroblasts correlated the HS2 element with transcriptional
      repression of the -2.3 kb promoter sequence. This last observation was further
      corroborated by showing that forced overexpression of GATA-4 in cultured
      fibroblasts leads to decreased transcription from the co-transfected -2.3 kb
      promoter/reporter construct, as well as reduced expression of the endogenous
      collagen gene. Finally, a chromatin immunoprecipitation assay documented GATA-4
      ability to bind to the HS2 element in vivo. These results are therefore the first
      to implicate GATA-4 in regulating constitutive COL1A2 gene expression in
      fibroblasts.

PMID- 15982864
TI  - Angiogenesis and lipoxins.
AB  - Angiogenesis, the growth of new capillaries from pre-existing ones, occurs
      through dynamic functions of the endothelial cells (EC), including migration,
      proliferation and maturation, which are essential to achieve an organized
      formation of the vessel sprout. Aspirin-triggered lipoxins (ATL), the 15R
      enantiomeric counterparts of native lipoxins, are endogenous lipid mediators
      generated within the vascular lumen during multicellular responses, which display
      potent and well-described immunomodulatory actions. Here we present some of the
      findings regarding the inhibition of EC responses in vitro and in vivo by these
      novel compounds and the modulation of fundamental steps of the angiogenic
      process, identifying previously unappreciated vascular actions of locally
      generated ATL and their longer acting synthetic analogs.

PMID- 15982865
TI  - A twist in anti-inflammation: annexin 1 acts via the lipoxin A4 receptor.
AB  - The inflammatory response is a life-saving protective process mounted by the body
      to overcome pathogen infection and injury; however, in chronic inflammatory
      pathologies this response can become deregulated. The existence of specialized
      anti-inflammatory pathways/mediators that operate in the body to down-regulate
      inflammation have now emerged. Thus, persistence of inflammation leading to
      pathology could be due to malfunctioning of one or more of these counter
      regulatory pathways. Here we focus on one of them, the anti-inflammatory mediator
      annexin 1, and provide an update on its inhibitory effects upon the leukocyte
      trafficking process. In particular, recent evidence that receptors of the formyl
      peptide family, which includes also the lipoxin A4 receptor, could be the annexin
      1 receptor(s) in the context of anti-inflammation might provide new avenues for
      exploiting this pathway for drug discovery.

PMID- 15982866
TI  - Development of a novel, multi-analyte biosensor system for assaying cell
      division: identification of cell proliferation/death precursor events.
AB  - A novel, miniaturized biosensor system was created by combining the
      electrophysiological response of immobilized cells with superoxide-sensing
      technology, optical and fluorescence microscopy. Vero cells were immobilized in a
      calcium alginate matrix (at a density of 1.7 x 10(6) cells ml(-1)). A 0.5 cm x
      0.5 cm piece of cell-containing gel matrix was aseptically adhered on a glass
      microscope slide with a microfabricated gold electrode array, sealed with a cover
      slip and provided with Dulbecco's medium +10% (v/v) fetal calf serum every day by
      means of a capillary feeding tube. During a culture period of 7 days, the
      membrane potential of immobilized cells was continuously monitored, while cell
      division was assayed with an optical microscope. In addition, daily measurements
      of immobilized cell membrane potential, viability, RNA and calcium concentration,
      radical oxygen species (ROS) and glutathione accumulation, were conducted by
      fluorescence microscopy after provision of an appropriate dye. Superoxide
      accumulation was assayed by covering the electrodes with superoxide dismutase
      (SOD). Maximum cell membrane potential values and superoxide production were
      observed upon initiation of cell division. Using the novel biosensor, we were
      able to correlate seven different cell physiological parameters to each other and
      formulate a model for ROS-mediated signaling function on cell division and death.
      In addition, we were able to predict cell proliferation or death by comparing the
      relative response of the electrophysiological and superoxide sensor during the
      culture period.

PMID- 15982867
TI  - The emerging family of hepatoblastoma tumours: from ontogenesis to oncogenesis.
AB  - The identification of distinct types and subtypes of hepatoblastoma has led to a
      successful classification of these lesions. In recent years, and particularly
      within large tumour trials, the spectrum of paediatric epithelial liver tumours
      has increased. This, together with the need for defining clinically relevant risk
      groups, will require a new approach to defining and classifying these cancers.
      Furthermore, an impressive amount of molecular biological information on liver
      ontogenesis and growth regulation of hepatic tumours has recently accumulated,
      which will allow the development of a comprehensive classification system with
      particular emphasis on prognostics. In this review, novel findings relating to
      these issues are discussed.

PMID- 15982868
TI  - Mechanisms of resistance to aromatase inhibitors.
AB  - Aromatase inhibitors are rapidly becoming the first choice for hormonal treatment
      of steroid receptor positive breast cancer in postmenopausal women. An
      understanding of the resistance mechanisms to these agents is, therefore,
      important for the appropriate delivery of treatment to responsive patients and
      the rational development of new agents targeted at the resistance pathways. De
      novo resistance appears to be a quantitative rather than qualitative phenomenon
      with virtually all oestrogen receptor positive tumours showing an anti
      proliferative response to the aromatase inhibitor anastrozole. While the
      expression of type 1 growth factor receptors reduces response to tamoxifen this
      appears to have little detrimental effect on response to aromatase inhibitors.
      Studies of acquired resistance in vitro have indicated that acquisition of
      hypersensitivity to oestrogenic stimulation is a key mechanism that is dependent
      on enhanced cross-talk of growth factor and oestrogen signaling pathways.
      Collection of resistant biopsy tissues from patients is important to determine if
      this mechanism is clinically relevant.

PMID- 15982869
TI  - Androgen receptor down regulation by small interference RNA induces cell growth
      inhibition in androgen sensitive as well as in androgen independent prostate
      cancer cells.
AB  - We investigated the effects of androgen receptor (AR) down regulation with a
      small interference RNA molecule (siRNA_AR(start)) on androgen sensitive LNCaP and
      androgen independent LNCaPabl prostate cancer cells, the latter representing an
      in vitro model for the development of therapy resistance in prostate cancer.
      Although LNCaPabl cells express increased levels of AR in comparison with
      androgen sensitive LNCaP cells, the protein was significantly down regulated in
      response to siRNA_AR(start) treatment. This AR down regulation resulted in a
      marked cell growth inhibition in both cell lines. By contrast, DU-145 prostate
      cancer cells, which lack AR expression, were not inhibited by the
      siRNA_AR(start). In consequence to AR down regulation, both cell lines, LNCaP and
      LNCaPabl, shared a highly similar gene expression profile in terms of major
      changes in cell cycle regulatory genes. The cell cycle inhibitor p21(Waf1/Cip1)
      as well as cyclin D1 were significantly up regulated by siRNA_AR(start)
      treatment, considering a switch in cyclin expression towards cell cycle
      retardation. Control molecules had moderate effects on cell proliferation and
      gene expression, respectively. In summary, we found that AR inhibition with siRNA
      induces cell growth retardation in androgen sensitive as well as in androgen
      independent prostate cancer cells and thus may represent an interesting approach
      to combat hormone-refractory prostate cancer.

PMID- 15982870
TI  - Phytoremediation of ethion by water hyacinth (Eichhornia crassipes) from water.
AB  - The potential of water hyacinth (Eichhornia crassipes) to remove a phosphorus
      pesticide ethion were investigated. The disappearance rate constants of ethion in
      culture solutions were 0.01059, 0.00930, 0.00294, and 0.00201 h-1 for the non
      sterile planted, sterile planted, non-sterile unplanted, and sterile unplanted
      treatment, respectively, which were significantly different and implied that
      plant uptake and phytodegradation contributed 69% and that of microbial
      degradation took up 12% to the removal of the applied ethion. The accumulated
      ethion in live water hyacinth plant decreased by 55-91% in shoots and 74-81% in
      roots after the plant growing 1 week in ethion free culture solutions, suggesting
      that plant uptake and phytodegradation might be the dominant process for ethion
      removal by the plant. This plant might be utilized as an efficient, economical
      and ecological alternative to accelerate the removal and degradation of agro
      industrial wastewater polluted with ethion.

PMID- 15982871
TI  - Synthesis of multitopic neoglycopeptides displaying recognition and detection
      motifs.
AB  - We describe herein the synthesis of cyclic decapeptide template displaying
      clustered carbohydrate recognition motifs and detection agent on spatially
      separated domains. Such multitopic labeled neoglycopeptides represent attractive
      tools for binding assays with carbohydrate binding proteins in glycomic research.

PMID- 15982872
TI  - Investigation of glycine alpha-ketoamide HCV NS3 protease inhibitors: effect of
      carboxylic acid isosteres.
AB  - The design and synthesis of tetrapeptide-based alpha-ketoamides containing prime
      side acid isosteres HCV NS3 protease inhibitors are described. Tetrazole,
      sulfonic acid, and N-sulfonylcarboxamids were demonstrated to be efficient
      carboxylic acid replacements. Further optimization yielded a series of potent HCV
      NS3 protease inhibitors with IC(50) of 0.020-0.060 microM.

PMID- 15982873
TI  - A preliminary study of the metabolic stability of a series of benzoxazinone
      derivatives as potent neuropeptide Y5 antagonists.
AB  - The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5
      antagonists, has been investigated. This study resulted in the identification of
      the structural moieties prone to metabolic transformations and which strongly
      influenced the in vitro half-life. This provides opportunities to optimize the
      structure of this new class of NPY Y5 antagonists.

PMID- 15982874
TI  - Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo-2'
      deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of
      human breast cancer cells.
AB  - One-electron oxidation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) yielded a
      guanidinohydantoin derivative (dGh) and a spiroiminodihydantoin derivative (dSp),
      both putatively mutagenic products that may be formed in vivo. The nucleoside dGh
      was the major product at room temperature, regardless of pH. The results are
      contrary to previously published model studies using 2',3',5'-triacetoxy-8-oxo
      7,8-dihydroguanosine (Luo, W.; Miller, J. G.; Rachlin, E. M.; Burrows, C. J. Org.
      Lett. 2000, 2, 613; Luo, W.; Miller, J.G.; Rachlin, E.M.; Burrows, C.J. Chem.
      Res. Toxicol. 2001, 14, 927), who observed a spiroiminodihydantoin derivative as
      the major product at neutral pH. Clearly, the functional groups attached to the
      ribose moiety of 8-oxodG influence the oxidation chemistry of the nucleobase
      derivative. To explore this chemistry in vivo, (14)C-labeled 8-oxodG was
      synthesized and incubated with growing MCF-7 human breast cancer cells, resulting
      in the incorporation of the compound into cellular DNA as measured by a novel
      accelerator mass spectrometry assay.

PMID- 15982875
TI  - Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1
      dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2
      oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent
      and selective melanocortin subtype-4 receptor agonist.
AB  - A novel isoquinuclidine containing selective melanocortin subtype-4 receptor
      small molecule agonist, 3 (RY764), is reported. Its in vivo characterization
      revealed mechanism-based food intake reduction and erectile activity augmentation
      in rodents.

PMID- 15982876
TI  - A macromolecular prodrug of doxorubicin conjugated to a biodegradable
      cyclotriphosphazene bearing a tetrapeptide.
AB  - A new biodegradable water-soluble phosphazene trimer-doxorubicin conjugate was
      synthesized, in which equimolar hydrophilic methoxy-poly(ethylene glycol) with a
      molecular weight of 350 (MPEG350) and a tumor-specific tetrapeptide (Gly-Phe-Leu
      Gly) were grafted to cyclotriphosphazene. The present conjugate exhibited
      cytotoxicity lower than that of free doxorubicin (IC50=0.10 microM) but a
      reasonably higher in vitro cytotoxicity (IC50=1.1 microM) against the leukemia
      L1210 cell line probably due to its enzymatically controlled release.

PMID- 15982877
TI  - Synthesis and SAR of 2-carboxylic acid indoles as inhibitors of plasminogen
      activator inhibitor-1.
AB  - We synthesized and evaluated a novel series of 2-carboxylic acid indole-based
      inhibitors of plasminogen activator inhibitor-1 (PAI-1). Systematic modification
      of the N-1 position and the 5-position of the indole scaffold resulted in the
      identification of several compounds that showed good potency against PAI-1 in the
      spectrophotometric assay. This potency did not always translate to the antibody
      assay. Solubility and serum protein binding studies on selected analogs revealed
      that protein binding might be a factor in the poor correlation between the two
      assays.

PMID- 15982879
TI  - 3-Thio-1,2,4-triazoles, novel somatostatin sst2/sst5 agonists.
AB  - Novel 3-thio-1,2,4-triazoles have been obtained via a solution-phase parallel
      synthesis strategy, affording potent non-peptidic human somatostatin receptor
      subtypes 2 and 5 agonists.

PMID- 15982878
TI  - Synthesis of 4(5)-phenylimidazole-based analogues of sphingosine-1-phosphate and
      FTY720: discovery of potent S1P1 receptor agonists.
AB  - The novel immunosuppressant FTY720 has been demonstrated to elicit
      immunomodulating effects via interaction with the G-protein coupled receptor
      S1P(1). FTY720 induced agonism at the S1P(3) receptor, however, has been shown to
      result in mild bradycardia, a minor side-effect of initial FTY720 therapy. This
      report describes the synthesis of several potent 4(5)-phenylimidazole-based
      S1P(1) receptor agonists that are accompanied by poor agonist activity at S1P(3).
      For instance, compound 20 displayed an EC(50)=4.7+/-1.3 nM at the S1P(1) receptor
      and EC(50)=780+/-1.3 nM at the S1P(3) receptor using a [gamma-(35)S]GTP-binding
      assay as compared to phospho-FTY720 (S1P(1): EC(50)=1.3+/-1.3nM, S1P(3):
      EC(50)=2.0+/-2.4 nM).

PMID- 15982880
TI  - P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K.
AB  - An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good
      pharmacokinetic properties has been identified. Starting from a potent inhibitor
      endowed with poor drug properties, conformational constraint of the P(2)-P(3)
      linker and modifications to P(1') elements led to an enhancement in potency,
      solubility, clearance, and bioavailability. These optimized inhibitors attenuated
      bone resorption in a rat TPTX hypocalcemic bone resorption model.

PMID- 15982881
TI  - Synthesis and structure-activity relationship of imidazo[1,2-a]benzimidazoles as
      corticotropin-releasing factor 1 receptor antagonists.
AB  - 8-Aryl-1,3a,8-triaza-cyclopenta[a]indenes represent a novel series of high
      binding affinity corticotropin-releasing factor 1 receptor antagonists. Here, we
      report their synthesis, SAR, and pharmacokinetic properties of compound 8e (K(i)
      = 23 nM).

PMID- 15982882
TI  - 2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs as
      adenosine A2A antagonists: the successful reduction of hERG activity. Part 2.
AB  - The structure-activity relationship (SAR) exploration using 2-(2-furanyl)-7
      phenyl[1,2,4]triazolo-[1,5-c]pyrimidin-5-amine (1) as a template led to the
      identification of a novel class of potent and selective adenosine A2A receptor
      (AR) antagonists. However, these compounds were found to be associated with
      significant hERG activity. This report discusses the strategy and outcome of an
      expanded SAR focused on addressing the hERG liability. As a result, compounds 21
      and 24 possess excellent in vitro profiles, highly promising in vivo profiles,
      and acceptable levels of hERG channel inhibition.

PMID- 15982883
TI  - Anxiolytic effects of benzalphthalides.
AB  - Anxiolytic effects induced by benzalphthalides on mice have been evaluated. The
      evaluation was based on the spent time and the number of entries of animals into
      the open arms in the elevated plus maze test. Single administration of
      benzalphthalides 1 and 11 induced significant increments in both parameters, thus
      revealing their potentiality as new leads for the development of non
      benzodiazepinic and non-nitrogenated antianxiety agents.

PMID- 15982884
TI  - Oral delivery of G protein-coupled receptor modulators: an explanation for the
      observed class difference.
AB  - G protein-coupled receptors (GPCRs) represent important targets for drug
      intervention. However, analysis of GPCR modulator drugs exhibits an important
      class difference, with many drugs available against aminergic GPCR targets, but
      relatively few against non-aminergic targets. The reason for this is that
      commonly drugs mimic the physicochemistry of the receptor ligand. Aminergic
      ligands generally exhibit physicochemical properties (molecular weight,
      lipophilicity and hydrogen bonding potential) that are consistent with extensive
      oral absorption. In contrast, non-aminergic ligands generally exhibit
      physicochemical properties that are at odds with oral delivery. Thus, combining
      required potency versus the receptor, with oral delivery potential is a
      significant challenge, and drug discovery becomes a question of finding the
      exceptional compound that lies at the edge of ADME space.

PMID- 15982886
TI  - Screen detected sclerosing lymphocytic lobulitis and amyloid of the breast in the
      same patient--a possible causal link.
AB  - Sclerosing lymphocytic lobulitis (SLL) and amyloidosis of the breast are both
      rare. We report the case of a 59 year old woman who presented with suspicious
      microcalcifications on routine screening mammography. Wire-guided excision biopsy
      showed features typical of SLL but also localised amyloid deposits within the
      specimen. Amyloidosis and SLL may have similar immunological causes. This patient
      represents the first documented association of these two disorders.

PMID- 15982887
TI  - Leukocyte migration: dismantling inhibition.
AB  - A new study demonstrates that the Src-family kinases Fgr and Hck inhibit
      chemokine signaling in polymorphonuclear leukocytes and dendritic cells by
      phosphorylation of PIR-B, an inhibitory receptor expressed on leukocytes. In
      resting cells, PIR-B phosphorylation is constitutive but is decreased transiently
      by addition of chemokines. In Fgr/Hck-deficient cells, constitutive PIR-B
      phosphorylation is markedly decreased. These Src-family kinases have a novel role
      in tonic inhibition of cell activation that must be overcome to allow the
      phenotypic effects of chemokine signaling through G-protein-coupled receptor
      ligands.

PMID- 15982888
TI  - Comparison of tap-evoked and tone-evoked postural reflexes in humans.
AB  - To find an easy clinical test of postural reflexes, we compared tone and tap
      stimuli for eliciting postural reactions in leg muscles in 13 healthy subjects
      during upright stance. Tones (1000 Hz, 90 dB nHl) were presented monaurally via
      headphones; taps were applied with a reflex hammer to the forehead. Surface EMG
      was recorded from the medial gastrocnemius and the sternocleidomastoid muscles,
      and rectified and averaged. Tapping the forehead of a standing subject evoked leg
      muscle reflexes that began 50 ms after the stimulus in all subjects. Tone-evoked
      leg muscle reflexes behaved differently, i.e., they had smaller amplitudes and
      could be recorded in only 5 of 13 subjects. However, this same acoustic stimulus
      elicited reflex activity in the neck muscles of all subjects. There were also
      other differences (amplitudes, dependence on pre-activation) between these two
      reflexes. Tone-evoked leg muscle responses and tone-evoked neck muscle responses
      seem to be mediated by different structures, i.e., the latter by an oligosynaptic
      pathway and the former by polysynaptic neural circuits. We conclude that tap
      evoked leg muscle responses are not or not solely mediated by saccular receptors
      but other receptors (i.e., proprioceptors, semicircular canals) are probably also
      involved.

PMID- 15982889
TI  - New genetic approaches shed light on TB virulence.
AB  - Although tuberculosis has been studied for more than a century, insights into the
      molecular mechanisms by which it causes disease remain fairly limited. The
      current genetic boom in this system promises to reveal new virulence mechanisms,
      making this an exciting time to be studying this disease. Long considered a
      technical "poor relation", tuberculosis research has developed into a source for
      creative techniques and ideas. In the midst of this development, it is important
      to keep in mind the limitations of each new approach that is employed to study
      this organism. This review examines the genetic approaches that are currently
      being used to study tuberculosis, with an emphasis on new developments that
      promise to improve our understanding of the pathogenic mechanisms of
      Mycobacterium tuberculosis.

PMID- 15982890
TI  - CT arteriography for orbital tumors: diagnostic and surgical value.
AB  - The aim of this study is to investigate the efficacy of dynamic computed
      tomography (CT) during selective angiography (CT-arteriography) of orbital tumors
      in the evaluation of intratumoral vascular anatomy, feeding artery territory, and
      histological diagnosis. Among 35 consecutive cases with various orbital lesions,
      those cases showing tumor staining or pooling of the contrast medium on digital
      subtraction angiography (DSA) were evaluated by CT-arteriography (n = 14). The
      information obtained by CT-arteriography was compared with that provided by
      enhanced MRI (n = 31) and dynamic MRI (n = 21), in which the contrast medium was
      injected intravenously. In addition to the visualization of fine vascular
      anatomy, CT-arteriography emphasized areas of nodular enhancement and non
      enhancing cystic/necrotic components as well as the intratumoral feeding
      arteries. Patterns of CT-arteriography were categorized into three subgroups:
      homogeneous enhancement (benign lymphoid lesion), partial enhancement
      (schwannomas and carcinomas), and patchy multinodular enhancement (specific for
      cavernous angiomas). In addition, CT-arteriography with selective arterial
      catheterization clearly delineated the feeding artery territories. CT
      arteriography, with a minimal dose of contrast medium, can offer significant
      advantages over intravenously injected dynamic neuroimaging, and provides
      additional valuable preoperative information about the orbital tumor under
      investigation.

PMID- 15982891
TI  - The stress-inducible displacement detected through RSA in non-migrating UKR.
AB  - Roentgen stereophotogrammetric analysis (RSA) under stress conditions was used to
      investigate possible stress-inducible displacement of the tibial component of
      unicompartmental knee prostheses (UKR) in which the stability was previously
      assessed by radiographic evaluation and standard supine RSA examinations. Sixteen
      patients, implanted with Duracon UNI(R) prosthesis, were selected for this study.
      The RSA protocol included examinations in plain upright standing posture and
      during execution of stress-inducing tasks in weight-bearing stance. The first
      follow-up was performed at an average of 14 months, and the second one at 26
      months. The results showed non-negligible stress-induced rotations of the
      prosthetic tibial component in all the patients in most of the stress tasks
      performed. Rotational stress tasks and squatting turned out to be the stress
      conditions in which induced displacement reached the most significant values
      (p<0.05). These micromotions occurred mainly around the transverse axis of the
      knee joint and in one examination around the sagittal axis. Stress-induced
      translations were negligible in all the examinations. Moreover, we focused our
      attention on two patients suffering from inexplicable pain, and we observed a
      significant difference in the inducible rotation around the x-axis between these
      patients and the remaining fourteen. Stress-inducible displacement is a common
      finding in knee prostheses, but we observed that in patients with inexplicable
      pain, these micromotions reached values greater than the median calculated on
      patients without any pain. This result suggests the introduction of the stress
      inducible displacement as a new parameter to be taken into consideration when
      analyzing the outcome of patients treated by UKR.

PMID- 15982892
TI  - Synthetic studies on oligosaccharides composed of 5-thioglucopyranose units.
AB  - Glycosylation reactions of 5-thioglucopyranosyl trichloroacetimidates bearing
      ethereal protective groups at the 2-O-position 14-15, and 37 proceed smoothly to
      give alpha-glycosides stereoselectively by using a catalytic amount of silyl
      triflate. This methodology allowed us to achieve syntheses of sulfur-substituted
      isomaltotetraoside 2 and maltotetraoside 3. These studies also revealed that
      benzoyl-protected 5-thioglucopyranosyl trichloroacetimidate 12 underwent beta
      selective glycosylation with C6-OH glucopyranosyl acceptors upon activation by
      BF3OEt2. This was applied for preparation of sulfur-substituted gentiobiosides 1
      and 46.

PMID- 15982893
TI  - Synthesis and pharmacological activities of some mononuclear Ru(II) complexes.
AB  - A series of mononuclear Ru(II) complexes of the type [Ru(M)2(U)]2+, where M =
      2,2'-bipyridine/1,10-phenanthroline and U = tpl (Ru1), 4-Cl-tpl (Ru2), 4-CH3-tpl
      (Ru3), 4-CH3O-tpl (Ru4), and 4-NO2-tpl (Ru5), -pai (Ru6), where tpl =
      thiopicolinanilide and pai = 2-phenyl-azo-imidazole, have been prepared and
      characterized by IR, UV-Vis, 1H NMR, 13C-NMR, FAB-Mass spectrophotometer, and
      elemental analysis. The complexes display metal-ligand charge transfer (MLCT)
      transitions in the visible region. The title complexes were subjected to in vivo
      anticancer activity tests against a transplantable murine tumor cell line,
      Ehrlich's ascitic carcinoma (EAC) and in vitro antibacterial activity against
      Gram positive and Gram negative microorganisms. Ru1-Ru6 were found to increase
      the life span of the tumor hosts by 19-52%, and decreased tumor volume and viable
      ascitic cell count. The results of the present study clearly demonstrated the
      tumor inhibitory activity of the ruthenium chelates against transplantable murine
      tumor cell line. The treatment with ruthenium complexes could be secondary to
      tumor regression or due to the action of the compounds itself. The significant
      antibacterial activity was observed for Ru1-Ru4 against microorganisms like
      Vibrio cholera 865, Staphylococcus aureus 6571, and Shigella flexneri as compared
      to that of standard drug chloramphenical. Ru5 showed moderate activity against S.
      aureus 8530. However, all the complexes fail to show significant antibacterial
      activity against V. cholera 14033 and Shigella sonnai.

PMID- 15982894
TI  - Determination of plutonium in environmental samples by AMS and alpha
      spectrometry.
AB  - Environmental samples from nuclear weapons test sites at the atolls of Mururoa
      and Fangataufa (French Polynesia, south Pacific) have been analyzed for their
      content of plutonium isotopes by applying the independent techniques of decay
      counting (Alpha Spectrometry) and accelerator mass spectrometry (AMS). Here, we
      propose the combination of both techniques which results in a maximum of
      information on the isotopic signature of Pu in environmental samples. Plutonium
      was chemically separated from the bulk material by anion exchange. (242)Pu was
      used as an internal standard for both AMS and alpha spectrometry. The samples for
      alpha spectrometry were prepared by micro-precipitation with NdF(3). After alpha
      spectrometry, the samples were reprocessed for AMS. Pu was co-precipitated with
      Fe(OH)(3) and finally, solid samples were prepared. At the VERA (Vienna
      Environmental Research Accelerator) facility, the various Pu isotopes were
      separated by their isotopic masses and quantified by the AMS technique. A good
      agreement of the results obtained from the AMS measurements was found with those
      obtained from Alpha Spectrometry. Overall, the data agree on average within 10%
      of each other. Isotope ratios for (238)Pu, (239)Pu and (240)Pu can be extracted
      from our investigations. Alpha spectrometry delivers data for the (238)Pu and the
      combination of ((239+240))Pu concentrations in those samples. In addition, the
      AMS technique provides information on the individual concentrations of (240)Pu
      and (239)Pu.

PMID- 15982895
TI  - Assessment of actinide mass embedded in large concrete waste packages by photon
      interrogation and photofission.
AB  - This paper describes a method based on photofission developed in our laboratory
      to characterize in depth large waste packages. The method consists in using
      photons of high-energy (Bremsstrahlung radiation) in order to induce reactions of
      photofission on the heavy nuclei present in the wastes. The measurement of the
      delayed neutrons allows quantifying the actinides in the wastes. We present the
      first results of measurement performed with a concrete mock-up of 870l and two
      real waste packages.

PMID- 15982897
TI  - Evaluation of hydrogen ion concentrations in prostates from rats and dogs using
      fluorescent confocal microscopy.
AB  - The knowledge of intracellular spatial distribution of pH in prostates in animal
      models reflective of human prostate may have implications for drug development
      upon pH dependent drug delivery and activity. Freshly dissected prostate tissues
      (in vitro) or the entire prostate gland (in vivo) were loaded with fluorescent
      dyes and viewed using confocal microscopy. Images were initially taken in tissues
      perfused with RPMI-1640 medium. Calibration in situ was performed with high
      potassium buffers of known pH containing nigericin. Acetoxymethyl ester carboxy
      SNARF-1 was visible in epithelial cells (but not stroma) in rat and dog
      prostates. The pH of lysosomes in prostate epithelial cells was 5.2 as determined
      by fluorescence of Lyso Sensor Green DND-189. A method of in situ confirmation of
      tissue viability was developed by a secondary loading and visualization of the
      BCECF fluorescent dye. Besides the direct measurement of the pH in rat and dog
      tissues (pH approximately 7.0), a method of pH measurement in prostate tissue
      (rather than in cell culture) was developed.

PMID- 15982898
TI  - Monitoring fluoropyrimidine metabolism in solid tumors with in vivo (19)F
      magnetic resonance spectroscopy.
AB  - (19)Fluorine magnetic resonance spectroscopy ((19)F MRS) offers unique
      possibilities for monitoring the pharmacokinetics of fluoropyrimidines in vivo in
      tumors and normal tissue in a non-invasive way, both in animals and in patients.
      This method may therefore be useful for predicting response to fluoropyrimidine
      based therapy with or without the effects of modulating agents, and this may be
      of value for the individualization of anticancer therapy and the strategic
      development of new anticancer drugs. (19)F MRS has been very valuable in
      elucidating the basic aspects of fluoropyrimidine metabolism, especially in
      animal studies. Studies in humans have indicated its clinical potential, but
      widespread application has been hampered by the relatively low detection
      sensitivity of the method. The recent introduction of clinical MR scanners with
      magnetic fields above 1.5 T may stimulate increased clinical use of (19)F MRS.

PMID- 15982899
TI  - Three-dimensional co-culture models to study prostate cancer growth, progression,
      and metastasis to bone.
AB  - Cancer-stromal interaction results in the co-evolution of both the cancer cells
      and the surrounding host stromal cells. As a consequence of this interaction,
      cancer cells acquire increased malignant potential and stromal cells become more
      inductive. In this review we suggest that cancer-stromal interaction can best be
      investigated by three-dimensional (3D) co-culture models with the results
      validated by clinical specimens. We showed that 3D culture promoted bone
      formation in vitro, and explored for the first time, with the help of the
      astronauts of the Space Shuttle Columbia, the co-culture of human prostate cancer
      and bone cells to further understand the interactions between these cells.
      Continued exploration of cancer growth under 3D conditions will rapidly lead to
      new discoveries and ultimately to improvements in the treatment of men with
      hormonal refractory prostate cancer.

PMID- 15982900
TI  - Expression and purification of recombinant antigens of Mycobacterium tuberculosis
      for application in serodiagnosis.
AB  - Accurate diagnosis is essential for the treatment, prevention, and control of
      tuberculosis. Poor specificity of the tuberculin skin test in BCG-vaccinated
      populations and constraints to implementation of PCR and CMI-based diagnostic
      assays in developing countries warrant development of easy-to perform robust
      serological tests. Due to great heterogeneity in humoral response in TB patients,
      it will be necessary to include several antigens in any diagnostic assay to
      achieve useful levels of sensitivity and specificity. This needs production of
      recombinants, soluble versions of mycobacterial antigens in high yields. We have
      cloned, expressed, and purified a number of mycobacterial proteins in Escherichia
      coli. This paper describes the expression and purification of four promising sero
      reactive proteins namely, ESAT6, CFP10, MTC28, and 14-kDa antigen of
      Mycobacterium tuberculosis. The protocol involves regulated and slow expression
      of proteins by using a T7 promoter-based expression vector for obtaining soluble
      protein followed by a three-step column chromatography procedure employing media
      with high binding capacity and flow characteristics. The yields of these proteins
      obtained were several folds higher than previously reported. The purified
      proteins were useful in detecting antibodies in sera of TB patients (smear
      positive, smear negative, and extra-pulmonary categories) and in combination with
      other immunodominant antigens will be useful in increasing the sensitivity to
      detect M. tuberculosis specific antibodies.

PMID- 15982901
TI  - Autism and the experience of a perceptual object.
AB  - Sewards and Sewards (2002) argue that while computations necessary for object
      recognition occur throughout the ventral visual stream, object recognition
      awareness involves the anterior temporal lobe and the medial orbital prefrontal
      cortex. The present paper suggests, however, that the medial orbital prefrontal
      cortex has a unique contribution, namely that of producing a basic experience of
      a perceptual object. It is further argued that the mechanisms that produce this
      experience also result in making the object more important than its subparts and
      features. Finally, it is argued that a reduction in this importance may account
      for some perceptual difficulties in high-functioning autism. This view is
      consistent with evidence for early selective abnormalities in other systems
      involving the medial prefrontal cortex in autism.

PMID- 15982902
TI  - The role of precuneus and left inferior frontal cortex during source memory
      episodic retrieval.
AB  - The posterior medial parietal cortex and left prefrontal cortex (PFC) have both
      been implicated in the recollection of past episodes. In a previous study, we
      found the posterior precuneus and left lateral inferior frontal cortex to be
      activated during episodic source memory retrieval. This study further examines
      the role of posterior precuneal and left prefrontal activation during episodic
      source memory retrieval using a similar source memory paradigm but with longer
      latency between encoding and retrieval. Our results suggest that both the
      precuneus and the left inferior PFC are important for regeneration of rich
      episodic contextual associations and that the precuneus activates in tandem with
      the left inferior PFC during correct source retrieval. Further, results suggest
      that the left ventro-lateral frontal region/frontal operculum is involved in
      searching for task-relevant information (BA 47) and subsequent monitoring or
      scrutiny (BA 44/45) while regions in the dorsal inferior frontal cortex are
      important for information selection (BA 45/46).

PMID- 15982903
TI  - Methodology used in safety pharmacology: appraisal of the state-of-the-art, the
      regulatory issues and new directions.
AB  - This is the second focused issue of the Journal of Pharmacological and
      Toxicological Methods that is devoted exclusively to methodology, opinions and
      regulatory issues related to Safety Pharmacology. This issue of the Journal
      highlights a record number of articles and abstracts from the 4th Annual Safety
      Pharmacology Society (SPS) meeting that was held in Covington, Kentucky September
      27-29, 2004. The focus of this issue of the Journal is to present a description
      of currently used fundamental pharmacological methods as outlined in the
      regulatory guidance documents for pre-clinical safety testing of drugs (ICH S7A
      and S7B). This issue features articles that discuss methods related to in vivo
      and in vitro CNS, respiratory and cardiovascular core battery studies.
      Additionally, articles are included that discuss species differences and
      recording issues in EKG measurement; automated (HTS) electrophysiology methods
      for assessing drug-induced hERG blockade (i.e., PatchXpress 7000A and hERG-lite);
      methods that describe and validate the use of the guinea pig as a safety
      pharmacology screening model; methods used to predict QTc prolongation and
      mathematical models that describe beat-to-beat instability of QT duration;
      supplemental studies that assess and discuss emerging renal biomarkers and renal
      function and food effects on gastrointestinal transit time; pro-arrhythmia
      models, cardiac function assessment using 3-D echocardiography and a description
      of a novel open field motor activity system to assess the possible CNS effects of
      drugs. Thus, this issue of the Journal of Pharmacological and Toxicological
      Methods should be a primary resource aid to individuals in academia and industry
      that are interested in understanding Safety Pharmacology methods. It provides a
      comprehensive overview of current and advanced methods used in Safety
      Pharmacology studies today.

PMID- 15982904
TI  - In vitro developmental expression of dystroglycan and laminin-alpha2 in human
      skeletal muscle.
AB  - The alpha-subunit of dystroglycan, a member of the dystrophin associated protein
      complex, binds to extracellular laminin-alpha2, while its beta-subunit interacts
      with cytoskeletal dystrophin. The exact biological role of dystroglycan,
      especially during human skeletal muscle development, has not been fully explored.
      Here, we analysed the distribution and expression characteristics of both
      dystroglycan subunits and laminin-alpha2 in primary human skeletal muscle cells.
      During development, expression levels of all three proteins increased with
      differentiation. The proteins were relocated from the sarcoplasm to the
      sarcolemma. The size of alpha-dystroglycan decreased from 150-220 kDa at the
      proliferation stage to 100-120 kDa at the late developmental stage. Both alpha-
      and beta-dystroglycan were involved in forming a complex with their respective
      partners laminin-alpha2 and dystrophin/utrophin. Our data show that, during
      development, cells may employ tightly regulated post-translational species
      specific modification to produce different isoforms of alpha-dystroglycan to
      participate in appropriate functions.

PMID- 15982905
TI  - A catalogue of abnormalities in the division spindles of higher plants.
AB  - This catalogue collates observations on meiotic division in a large number of
      plant forms with abnormal meiosis, including mutants, wide hybrids, haploids,
      polyploids, aneuploids, and alloplasmics. The process of division spindle
      formation remains relatively unexplored in the "centrosomeless" world of higher
      plant cells. Thus, analysis of abnormal spindles, each of which is a result of an
      aberration of a distinct prometaphase stage, is informative. A catalogue of
      spindle abnormalities is also useful for analysing the morphological phenotype of
      the corresponding mutations, especially insertional ones. It is particularly
      worthwhile for those organisms that are less than ideal for cytological analysis,
      e.g. Arabidopsis. In the catalogue, abnormal spindles are listed in relation to
      the time of the manifestation of aberrations that caused them.

PMID- 15982906
TI  - Gender specificity of programmed plasma hypertonicity and hemoconcentration in
      adult offspring of water-restricted rat dams.
AB  - OBJECTIVE: We studied the impact of maternal water-restriction during rat
      pregnancy on newborn plasma composition, and determined the persistence of plasma
      composition alterations in adult offspring. METHODS: Maternal dams were water
      restricted from 10 days of pregnancy until term (21 days) and throughout
      lactation to increase plasma sodium levels by approximately 6 mEq/L. At 21 days
      of age, offspring were weaned, and subsequently maintained on ad libitum food and
      water until 12 weeks of age. Daily water and food intake was monitored. Blood
      samples and organs were collected from 1-day- and 12-week-old offspring.
      Hematocrit, plasma osmolality, sodium, and arginine vasopressin (AVP) levels were
      analyzed. Because water-restriction led to concomitant reduction in maternal food
      intake (ie, dehydration anorexia), henceforth these dams and their offspring are
      referred to as "water-deprived/food-reduced" rats. RESULTS: Water-deprived/food
      reduced dams had significantly increased plasma sodium levels, reduced food
      intake, and lower body weight gain during pregnancy and lactation as compared to
      control dams. One-day-old newborns of water-deprived/food-reduced dams weighed
      17% less and had increased plasma sodium levels, osmolality, and hematocrit. At
      12 weeks of age, males exhibited 11% and females 19% reduction in body weight
      from controls. Notably, male offspring of water-deprived/food-reduced dams showed
      significantly elevated plasma sodium levels, osmolality, and hematocrit.
      Additionally, males demonstrated reduced adrenal growth and decreased water
      intake. Conversely, the female offspring had similar plasma osmolality with
      decreased sodium levels, though a persistently elevated hematocrit. No
      differences were evident in plasma AVP levels. CONCLUSIONS: Maternal water
      deprivation/food reduction is associated with increased newborn plasma osmolality
      and sodium levels and long-term physiologic changes in the offspring. The gender
      specificity of programmed hyperosmolality, though not hemoconcentration,
      implicates differing pathways/mechanisms for these phenotypic alterations. The
      contributions of pregnancy hypertonicity versus nutrient restriction in the
      mechanism for programmed offspring phenotype remain to be elucidated.

PMID- 15982907
TI  - Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in
      fetal guinea pig hearts.
AB  - OBJECTIVES: The underlying cellular mechanisms mediating hypoxia-induced
      adaptations in the fetus are poorly understood. We tested the hypothesis that
      hypoxia up-regulates endothelial nitric oxide synthase (NOS3, type III) protein
      expression in fetal hearts similar to that observed in adult hearts as a
      cardioprotective adaptation. This study investigates the effect of chronic
      hypoxia on NOS3 protein expression in hearts and carotid arteries of fetal guinea
      pigs exposed to normoxia or intrauterine hypoxia. METHODS: Time-mated pregnant
      guinea pigs (term = 65 days) were housed in either normoxic room air (NMX) or
      exposed to 12% O(2) (hypoxia; HPX) for 14 or 28 days of duration. At near term (
      approximately 60 days of gestation), pregnant mothers were anesthetized and fetal
      guinea pig hearts and carotid arteries were excised from NMX and HPX animals and
      frozen until ready for study. In addition, hearts were also excised from
      anesthetized adult nonpregnant female guinea pigs exposed to either NMX or HPX
      for 14 days. NOS3 protein was extracted from all tissues and quantified using
      Western blot analysis. Fetal heart samples were also prepared for localization of
      NOS3 protein using immunohistochemistry. RESULTS: Chronic hypoxia increased both
      maternal and fetal hematocrit after 28 days of duration. HPX decreased NOS3
      protein levels in fetal guinea pig hearts by 29% after 28 days compared to NMX
      controls. In contrast, HPX increased both NOS3 protein levels in adult hearts by
      62% and fetal carotid arteries by fourfold after 14 days of exposure compared to
      their respective NMX controls. Positive immunostaining of NOS3 protein of fetal
      hearts was localized in both cardiomyocytes and endothelial cells. CONCLUSION:
      Contrary to our hypothesis, the hypoxia-induced decrease in fetal guinea pig
      heart NOS3 protein contrasts to the protein levels measured in either adult
      hearts or fetal carotid arteries. These results suggest that the NOS protein
      expression is altered differently by hypoxia in fetal and adult hearts and in a
      peripheral fetal artery exposed to the same level of hypoxia. Thus, the
      functional role of NO in the fetal heart during hypoxia may differ from that of
      the adult.

PMID- 15982908
TI  - Accumulation of MFG-E8/lactadherin on exosomes from immature dendritic cells.
AB  - Exosomes are vesicles of endocytic origin secreted spontaneously by dendritic
      cells (DCs). We have shown previously that exosomes can transfer antigen or MHC
      peptide complexes between DCs, thus potentially amplifying the immune response.
      We had also identified milk fat globule EGF/factor VIII (MFG-E8), also called
      lactadherin, as one of the major exosomal proteins. MFG-E8 has two domains: an
      Arg-Gly-Asp sequence that binds integrins alphavbeta3 and alphavbeta5 (expressed
      by human DCs and macrophages) and a phosphatidyl-serine (PS) binding sequence
      through which it associates to PS-containing membranes (among which exosomes).
      MFG-E8 is thus a good candidate molecule to address exosomes to DCs. Here, we
      show that MFG-E8 is expressed by immature bone-marrow-derived DCs (BMDCs) and
      secreted in association with exosomes in vitro. We have generated mice expressing
      an inactive form of MFG-E8, fused to beta-galactosidase. Analyzing these mice, we
      demonstrate that MFG-E8 is expressed in vivo in splenic DCs. In a mouse DC
      dependent, antigen-specific, CD4 T cell-stimulation assay, exosomes produced by
      MFG-E8-deficient BMDCs were barely less efficient than exosomes bearing MFG-E8.
      We conclude that MFG-E8 is efficiently targeted to exosomes but is not essential
      to address exosomes to mouse BMDCs. Involvement of MFG-E8/lactadherin in exosome
      targeting to other DC subpopulations, or to human DCs, is still possible.

PMID- 15982909
TI  - Compound heterozygote states for Hb C/Hb Malay and Hb C/Hb E in pregnancy: a
      molecular and hematological analysis.
AB  - Hemoglobin (Hb) C (alpha2beta(2)6Glu-Lys) is a variant Hb found mainly in West
      Africa where individuals carrying both Hb C and Hb S (alpha2beta(2)6Glu-Val)
      usually have a disease similar to sickle cell disease. The Hb C molecule has
      reduced solubility leading to crystal formation and hemolytic anemia. We report a
      hitherto undescribed interaction of Hb C and Hb Malay (alpha2beta(2)19Asn-Ser) in
      a Thai individual. She was a 24-year-old pregnant woman with moderate anemia who
      had the following hematologic data; Hb 8.9 g/dl, Hct 30.0%, MCV 81.0 fl, MCH 24.1
      pg, MCHC 29.7 g/dl, RDW 17.1% and instead of Hb crystal a marked number of target
      cell in peripheral blood was observed. Hb analysis revealed 22.5% Hb Malay, 64.6%
      Hb C and 4.5% Hb A2. Globin gene analyses demonstrated that she carried the betaC
      mutation (beta6: GAG-AAG) in trans to the betaMalay mutation (beta19: AAC-AGC).
      Hematologic data of the patient were compared to those of the compound
      heterozygote for Hb C and Hb E (alpha2beta(2)26Glu-Lys) found in 5 other
      unrelated Thai pregnant women and 11 pregnant women with Hb C heterozygote with
      or without co-inheritance of alpha-thalassemia who had much lower Hb C levels and
      the non-pregnant women with Hb C heterozygote and a compound Hb E/Hb Malay
      syndrome. Different genotype-phenotype correlations observed in these Thai
      patients with Hb C disorders are illustrated.

PMID- 15982910
TI  - Maternal and fetal effects of propofol anaesthesia in the pregnant ewe.
AB  - The objective of this study was to determine the effects of propofol (PRF) on
      maternal and fetal cardiopulmonary function during the last trimester of
      pregnancy. Six pregnant 2-3 year-old Ripollesa sheep, each weighing 78+/-8 kg
      were used in the study and prepared by placing catheters in the maternal jugular
      vein and carotid artery. A catheter was also placed in the fetal femoral artery.
      Twenty-four hours later the sheep were anaesthetized with PRF (6 mg/kg
      intravenous (IV) followed by a continuous infusion at a rate of 0.4 mg/kg/min for
      60 min) and cardiopulmonary data collected. Further data were collected for 105
      min following termination of the infusion. The maternal mean arterial pressure
      (MAP) and diastolic arterial pressure (DAP) were significantly decreased (P<0.05)
      during the first 15 min of the infusion period, while the maternal pH was also
      significantly decreased. Maternal PaCO(2) and PaO(2) were significantly increased
      throughout the total infusion period. It was further observed that the fetal pH
      decreased significantly, throughout the infusion period, whereas the fetal MAP,
      DAP and PaCO(2) were significantly increased during the first 15 min of the
      infusion, after which time all parameters returned to control values. No
      differences in either maternal or fetal parameters were observed between control
      and recovery times.

PMID- 15982911
TI  - Animal breeding and genomics: perspectives for dog breeding.

PMID- 15982912
TI  - NO modulation of myocardial performance in fish hearts.
AB  - In the mammalian heart, intracardiac nitric oxide (NO) regulates in an autocrine
      paracrine manner cardiac function in the beat-to-beat response (Starling's law of
      the heart), short-term response (phasic control, e.g. excitation-contraction
      coupling, responses to neurotransmitters and endocrines) and long-term response
      (tonic control by altering gene expression). This trio of NO temporal-dependent
      actions has a long evolutionary history, as we have documented in the prototypic
      vertebrate heart, the teleost heart. This heart shares a common structural and
      functional scenario with higher vertebrate hearts exhibiting, at the same time,
      differences in myoarchitecture (trabecular vs. compact type), blood supply
      (lacunary vs. vascular) and pumping performance (sensitivity to filling
      pressure), thus providing challenging opportunities for revealing aspects of
      unity and diversity of cardiac NO in vertebrates. Using in vitro working teleost
      heart preparations we have shown that, under basal conditions, NO through a cGMP
      mediated mechanism modulates ventricular performance (negative inotropism) and
      remarkably increases the sensitivity to filling pressure (i.e. the Frank-Starling
      response). NO-cGMP mechanism also influences the short-term response elicited by
      inotropic agents such as acetylcholine and angiotensin II. A role of NO in long
      term cardiac adaptation is illustrated by morphologic evidence (e.g. NOS immuno
      localization in phylogenetically distant species) which emphasizes the importance
      of NO in reshaping the angio-myoarchitecture of the fish heart ventricle (i.e.
      compensation for regional heterogeneity). Finally, by studying the avascular
      hearts of teleosts and amphibians that lack vascular endothelium, a relevant role
      of endocardial endothelium-NO signalling in intracavitary regulation of
      myocardial performance has been firmly established, thus revealing its early
      evolutionary role in non-mammalian vertebrates.

PMID- 15982913
TI  - Neuropeptide Y content in the hypothalamic paraventricular nucleus responds to
      fasting and refeeding in broiler chickens.
AB  - To examine the neural mechanism by which hypothalamic neuropeptide Y (NPY)
      regulates energy homeostasis and feeding behavior in commercial broilers, we
      measured NPY content in several hypothalamic regions of birds that were fasted
      and then refed. After fasting for 48 and 72 h, body weight significantly
      decreased, and food intake significantly increased during the subsequent
      refeeding. The lost body weight was not restored to ad libitum feeding levels
      even after 3 days of refeeding. Plasma glucose concentration and body fat content
      significantly decreased and plasma non-esterified fatty acid (NEFA) concentration
      significantly increased after 48- and 72-h fasting. Refeeding for 24 h restored
      plasma metabolites and body fat content to pre-fasting levels. NPY content in the
      paraventricular nucleus (PVN) and infundibular nucleus significantly increased
      during fasting, and NPY content of the PVN was restored to pre-fasting levels
      after 24-h refeeding. However, there was no significant change in the NPY content
      of the lateral hypothalamic area during fasting or refeeding. The present results
      of changes in the hypothalamic NPY content during fasting and refeeding support
      the hypothesis that NPY plays a central role in regulation of energy homeostasis,
      with especially important effect on feeding behavior and body weight in broiler
      chickens.

PMID- 15982914
TI  - The role of nitric oxide in regulation of the cardiovascular system in reptiles.
AB  - The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles
      are reviewed, with particular emphasis on its effects on central vascular blood
      flows in the systemic and pulmonary circulations. New data is presented that
      describes the effects on hemodynamic variables in varanid lizards of exogenously
      administered NO via the nitric oxide donor sodium nitroprusside (SNP) and
      inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l
      NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic
      variables in the tegu lizard are presented. The findings are compared with
      previously published data from our laboratory on three other species of reptiles:
      pythons (), rattlesnakes () and turtles (). These five species of reptiles
      possess different combinations of division of the heart and structural complexity
      of the lungs. Comparison of their responses to NO donors and NOS inhibitors may
      reveal whether the potential contribution of NO to vascular tone correlates with
      pulmonary complexity and/or with blood pressure. All existing studies on reptiles
      have clearly established a potential role for NO in regulating vascular tone in
      the systemic circulation and NO may be important for maintaining basal systemic
      vascular tone in varanid lizards, pythons and turtles, through a continuous
      release of NO. In contrast, the pulmonary circulation is less responsive to NO
      donors or NOS inhibitors, and it was only in pythons and varanid lizards that the
      lungs responded to SNP. Both species have a functionally separated heart, so it
      is possible that NO may exert a larger role in species with low pulmonary blood
      pressures, irrespective of lung complexity.

PMID- 15982915
TI  - Tendency for oxidation of annelid hemoglobin at alkaline pH and dissociated
      states probed by redox titration.
AB  - The redox titration of extracellular hemoglobin of Glossoscolex paulistus
      (Annelidea) was investigated in different pH conditions and after dissociation
      induced by pressure. Oxidation increased with increasing pH, as shown by the
      reduced amount of ferricyanide necessary for the oxidation of hemoglobin. This
      behavior was the opposite of that of vertebrate hemoglobins. The potential of
      half oxidation (E1/2) changed from -65.3 to +146.8 mV when the pH increased from
      4.50 to 8.75. The functional properties indicated a reduction in the log P50 from
      1.28 to 0.28 in this pH range. The dissociation at alkaline pH or induced by high
      pressure, confirmed by HPLC gel filtration, suggested that disassembly of the
      hemoglobin could be involved in the increased potential for oxidation. These
      results suggest that the high stability and prolonged lifetime common to
      invertebrate hemoglobins is related to their low tendency to oxidize at acidic
      pH, in contrast to vertebrate hemoglobins.

PMID- 15982916
TI  - Soluble organic matrix of two Scleractinian corals: partial and comparative
      analysis.
AB  - This study is a biochemical and molecular analysis of the soluble organic matrix
      (SOM) of two Scleractinian corals differing in their morphological
      characteristics: Stylophora pistillata, a branched robust coral and Pavona
      cactus, a leafy complex coral. Soluble organic matrix of both coral species were
      shown to contain high amounts of potentially acidic amino acids and glycine.
      However, proportions of glycosaminoglycans and SDS-PAGE analyses of soluble
      organic matrix proteins were very different. Three proteins of S. pistillata and
      at least five proteins of P. cactus were detected by silver staining, some of
      them being able to bind calcium. Internal peptide sequences of two matrix
      proteins (one from each species) were obtained. One sequence of S. pistillata is
      unusual because it contains a long poly-aspartate domain, as described in
      proteins belonging to the calsequestrin family and in proteins from molluscan
      species. This domain suggests an essential role for this protein in the control
      of mineralization.

PMID- 15982917
TI  - Lymphocytic joint fluid in tuberculous arthritis. A review of 30 cases.
AB  - Several cases of tuberculous arthritis with lymphocytic joint fluid have been
      reported. This may explain in part the insidious course of tuberculous arthritis.
      We studied the characteristics of lymphocytic fluid from joints affected with
      tuberculosis and we looked for specific clinical, radiological, or laboratory
      test features, comparatively to patients with neutrophilic joint fluid. PATIENTS
      AND METHODS: We retrospectively reviewed the medical records of 30 patients with
      tuberculous arthritis, 20 men and 10 women with a mean age of 47.7+/-21.4 years
      (10-75) and a mean symptom duration at diagnosis of 25.7+/-27.6 months (2-120).
      RESULTS: Mean joint fluid leukocyte count was 15,181+/-15,635 per mm3 (600
      40,000). In joint fluid, neutrophils predominated in 24 patients and lymphocytes
      in six (20%) patients. Blood cell counts showed no predominance of lymphocytes.
      No specific clinical, radiological, or laboratory test features were noted in the
      group with lymphocytic joint fluid. CONCLUSION: We found that a predominance of
      lymphocytes in joint fluid from patients with tuberculous arthritis was uncommon
      and was not associated with specific features.

PMID- 15982918
TI  - Impaired trafficking of mutants of lysosomal glucocerebrosidase in Gaucher's
      disease.
AB  - Gaucher's disease is the most inherited lysosomal storage disorder. Except for a
      few cases, the broad phenotypic heterogeneity of Gaucher's disease can be neither
      predicted from defined mutations nor from differences in residual enzyme
      activity. Here, we analyse the intracellular trafficking of glucocerebrosidase as
      an underlying mechanism for the expression of the clinical phenotype.
      Biosynthetic labeling studies combined with immunofluorescence analyses with
      fibroblasts from patients with the defined mutations N370S, L444P, D409H and
      G202R unequivocally demonstrate a retarded transport of glucocerebrosidase
      carrying the mutation N370S and a transport block in the ER of the enzyme with
      the mutations G202R, L444P and D409H. We asked whether cellular components in the
      patients' fibroblasts other than glucocerebrosidase are implicated in the onset
      of the disease. For this, mutant cDNA's corresponding to the phenotypes N370S,
      G202R and L444P were expressed in the mouse fibroblasts NIH3T3. Essentially
      similar biochemical and cellular features were revealed as compared to the
      patients' fibroblasts strongly suggesting that these mutations are exclusively
      responsible for the characterized phenotypes. Interestingly, the immunoglobulin
      binding protein (BiP) binds wild type and the mutant N370S but not the G202R and
      L444P variants suggesting a discriminatory role played by this chaperone
      associated with the severity of the disease.

PMID- 15982919
TI  - Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle
      and heart.
AB  - Chronic alcohol abuse has the potential to modulate striated muscle physiology
      and function. The skeletal muscle alcoholic myopathy is characterized by muscle
      weakness and difficulties in gait and locomotion, while chronic alcohol
      consumption ultimately leads to a decrease in cardiac contractility and output.
      In both tissues a loss of protein mass results in part from a decreased protein
      synthesis that initially manifests as a defect in translational efficiency. This
      review focuses on recent developments in understanding the cellular and molecular
      mechanisms by which alcohol impairs mRNA translation in skeletal and cardiac
      muscle, including identification of the signaling pathways and biochemical sites
      negatively impacted. Defective signaling potentially results from resistance to
      the normal stimulating effects of anabolic hormones (insulin and insulin-like
      growth factor-I) and nutrients (leucine) as well as increased production of
      several negative regulators of muscle mass. Overall, the biochemical mechanisms
      contributing to the pathogenesis of loss of skeletal and cardiac muscle are
      reviewed.

PMID- 15982920
TI  - Cellular signals activating muscle proteolysis in chronic kidney disease: a two
      stage process.
AB  - Muscle atrophy is a prominent feature of catabolic conditions and in animal
      models of these conditions there is accelerated muscle proteolysis that is
      dependent on the ubiquitin-proteasome system. However, ubiquitin system cannot
      degrade actomyosin or myofibrils even though it rapidly degrades actin or myosin.
      We identified caspase-3 as the initial and potentially rate-limiting proteolytic
      step that cleaves actomyosin/myofibrils. In rodent models of catabolic
      conditions, we find that caspase-3 is activated to cleave muscle proteins and
      actomyosin to fragments that are rapidly degraded by the ubiquitin system. This
      initial proteolytic step in muscle can be recognized because it leaves a
      footprint of a characteristic 14-kDa actin band. Stimulation of caspase-3
      activity depends on activation of phosphatidylinositol 3-kinase. When we
      suppressed this enzyme in muscle cells, protein breakdown increased as did the
      expression of caspase-3. In addition, there was increased expression of E3
      ubiquitin-conjugating enzymes that are involved in muscle proteolysis, atrogin
      1/MAFbx and MuRF1. Thus, when phosphatidylinositol 3-kinase activity is low in
      muscle cells or rat muscle, both caspase-3 and the ubiquitin-proteasome system
      are stimulated to degrade protein. Additional investigations will be needed to
      define the cell signaling processes that activate muscle proteolysis in uremia
      and catabolic conditions.

PMID- 15982921
TI  - RET tyrosine kinase signaling in development and cancer.
AB  - The variety of diseases caused by mutations in RET receptor tyrosine kinase
      provides a classic example of phenotypic heterogeneity. Gain-of-function
      mutations of RET are associated with human cancer. Gene rearrangements
      juxtaposing the tyrosine kinase domain to heterologous gene partners have been
      found in sporadic papillary carcinomas of the thyroid (PTC). These rearrangements
      generate chimeric RET/PTC oncogenes. In the germline, point mutations of RET are
      responsible for multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial
      medullary thyroid carcinoma (FMTC). Both MEN 2 mutations and PTC gene
      rearrangements potentiate the intrinsic tyrosine kinase activity of RET and,
      ultimately, activate the RET downstream targets. Loss-of-function mutations of
      RET cause Hirschsprung's disease (HSCR) or colonic aganglionosis. A deeper
      understanding of the molecular signaling of normal versus abnormal RET activity
      in cancer will enable the development of potential new treatments for patients
      with sporadic and inherited thyroid cancer or MEN 2 syndrome. We now review the
      role and mechanisms of RET signaling in development and carcinogenesis.

PMID- 15982922
TI  - Mediterranean Diplodus annularis (Teleostei: Sparidae) and its brain parasite:
      unforeseen outcome.
AB  - Patterns of parasite load and aggregation of the bird trematode Cardiocephaloides
      longicollis in its main intermediate host in the Mediterranean, the annular sea
      bream, Diplodus annularis, were studied in a large sample collected off Valencia
      (Spain) and are discussed within the context of the parasite induced host
      mortality hypothesis. The metacercariae were located within large composite cysts
      of host origin in the ventricles of the optic lobes of the cerebrum. A weak
      immunological response was detected in older fish, which was significantly
      associated with the total parasite load. Although the mean abundance of C.
      longicollis showed a tendency to increase with host size, the infection levels
      were generally homogeneous with a noticeable plateauing in the intermediate size
      classes. The distribution of the metacercariae was aggregated and agreed with the
      negative binomial distribution. There was a marked decline in parasite
      aggregation in the largest size-class, suggesting parasite-induced host mortality
      in the oldest fish possibly due to predation by large non-host fish predators. On
      the other hand, levelling off of abundance and decrease in heterogeneity of
      parasite distribution within the intermediate age cohort could indicate that
      these sizes are being rapidly and/or constantly removed from the host population
      due to by-catch fishing. The overall high infection levels and the continuous
      recruitment across age cohorts provides evidence that an enhanced parasite
      transmission is taking place in the Gulf of Valencia due to increased spatial
      overlap of the hosts involved in the life cycle. We suggest a human-induced
      facilitation of the digenean life cycle due to the fact that gulls in the area
      feed extensively on discards, thus indicating the possibility of an unforeseen
      effect of fishing practices in a marine littoral system.

PMID- 15982923
TI  - Spectroscopic and theoretical study of Cu(II), Zn(II), Ni(II), Co(II) and Cd(II)
      complexes of glyoxilic acid oxime.
AB  - The paper presents a detailed experimental and theoretical study of five metal
      complexes of glyoxilic acid oxime (gaoH2), Cu(gaoH)2(H2O)2 (1), Zn(gaoH)2(H2O)2
      (2), Co(gaoH)2(H2O)2 (3), Ni(gaoH)2(H2O)2 (4) and [Cd(gaoH)2(H2O)2].H2O (5). The
      electronic and vibrational spectra were measured and discussed as to the most
      sensitive to the M-L binding bands. Two different types of coordination were
      considered for gaoH- ligand: bidentate through the carboxylic oxygen and oxime
      nitrogen in 1-4 and mixed bidentate and bridging through the COO group in 5. It
      is shown that the spectral behavior of the nu(COO) modes can be used to predict
      bridging ligand coordination. DFT(B3LYP/6-31++G(d,p)) calculations on model
      compounds: neutral, anionic and radical forms of gao and Cu(gaoH)2, have been
      carried out to correlate geometries, electronic and vibrational structures. The
      results obtained were used to assist the electronic and vibrational analysis of
      the complexes studied. The effect of the metal-ligand interactions (electrostatic
      and covalent) on the geometry structure of the ligand was investigated.

PMID- 15982925
TI  - Atypical EEG findings in subacute sclerosing panencephalitis.
AB  - OBJECTIVE: To evaluate atypical electroencephalographic features in subacute
      sclerosing panencephalitis (SSPE) and to detect its relation to clinical
      features. METHODS: Twenty-two patients aged 2-17 years (mean 9.4 years) with
      definite diagnosis of SSPE were studied. Their clinical data and EEG records were
      reviewed retrospectively. All EEG records were analysed for features of periodic
      complexes (PCs) in relation to age, age at onset, clinical stage and the rate of
      progression as well as duration of the disease. RESULTS: Classical periodic
      complexes of SSPE were found in EEGs of 13 patients (group I). Atypical patterns
      were observed in EEGs of nine patients (group II). Two new atypical findings were
      identified: prolonged discharges which include sharp waves and slow waves for 4-7
      s followed by suppression for 1-4s; and periodic complexes which consist of four
      or five sharp waves in every 2 s. We observed atypical EEG patterns were more
      frequently in Stage III, acute form, and the disease duration was longer than in
      the typical group. CONCLUSIONS: Atypical EEG patterns in SSPE might be related to
      the progression of the disease, but this theory needs further longitudinal
      studies. SIGNIFICANCE: We suggest atypical EEG patterns might be observed more
      frequently in patients with severe neurologic disability, more rapidly
      progressive disease and longer duration of disease.

PMID- 15982924
TI  - Pulmonary surfactant protein A inhibits the lipid peroxidation stimulated by
      linoleic acid hydroperoxide of rat lung mitochondria and microsomes.
AB  - Reactive oxygen species play an important role in several acute lung injuries.
      The lung tissue contains polyunsaturated fatty acids (PUFAs) that are substrates
      of lipid peroxidation that may lead to loss of the functional integrity of the
      cell membranes. In this study, we compare the in vitro protective effect of
      pulmonary surfactant protein A (SP-A), purified from porcine surfactant, against
      ascorbate-Fe(2+) lipid peroxidation stimulated by linoleic acid hydroperoxide
      (LHP) of the mitochondria and microsomes isolated from rat lung; deprived
      organelles of ascorbate and LHP were utilized as control. The process was
      measured simultaneously by chemiluminescence as well as by PUFA degradation of
      the total lipids isolated from these organelles. The addition of LHP to rat lung
      mitochondria or microsomes produces a marked increase in light emission; the
      highest value of activation was produced in microsomes (total chemiluminescence:
      20.015+/-1.735 x 10(5) cpm). The inhibition of lipid peroxidation (decrease of
      chemiluminescence) was observed with the addition of increasing amounts (2.5 to
      5.0 microg) of SP-A in rat lung mitochondria and 2.5 to 7.5 microg of SP-A in rat
      lung microsomes. The inhibitory effect reaches the highest values in the
      mitochondria, thus, 5.0 microg of SP-A produces a 100% inhibition in this
      membranes whereas 7.5 microg of SP-A produces a 51.25+/-3.48% inhibition in
      microsomes. The major difference in the fatty acid composition of total lipids
      isolated from native and peroxidized membranes was found in the arachidonic acid
      content; this decreased from 9.68+/-1.60% in the native group to 5.72+/-1.64% in
      peroxidized mitochondria and from 7.39+/-1.14% to 3.21+/-0.77% in microsomes.
      These changes were less pronounced in SP-A treated membranes; as an example, in
      the presence of 5.0 microg of SP-A, we observed a total protection of 20:4 n-6
      (9.41+/-3.29%) in mitochondria, whereas 7.5 microg of SP-A produced a 65%
      protection in microsomes (5.95+/-0.73%). Under these experimental conditions, SP
      A produces a smaller inhibitory effect in microsomes than in mitochondria.
      Additional studies of lipid peroxidation of rat lung mitochondria or microsomes
      using equal amounts of albumin and even higher compared to SPA were carried out.
      Our results indicate that under our experimental conditions, BSA was unable to
      inhibit lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung
      mitochondria or microsomes, thus indicating that this effect is specific to SP-A.

PMID- 15982926
TI  - Scalp electrode placement by EC2 adhesive paste in long-term video-EEG
      monitoring.
AB  - OBJECTIVE: To evaluate the usefulness of an adhesive paste named EC2 (Grass
      Telefactor) in comparison with collodion, for scalp electrodes placement in
      patients with drug resistant partial epilepsy monitored by long-term video-EEG.
      METHODS: A total of 40 patients with drug resistant partial epilepsy participated
      in the study. In 20 patients, electrode placement on the scalp was made with
      collodion (group C) whereas in the remaining patients EC2 was used (Group P).
      After the electrode placement (T1) and after 24 h of recording (T2), the
      impedance of the electrodes was measured. Moreover, the time required to apply
      the electrodes and for their daily maintenance was calculated and recorded for
      all patients who entered the study. RESULTS: At each observation, group C showed
      mean values of electrode impedance significantly higher that the group P (T1:
      16.8 k omega; T2: 6.5 k omega vs T1: 2.4 k omega; T2: 4.0 k omega, respectively)
      (P < 1 x 10(-5)). The time required to make the montage and to provide its daily
      maintenance was significantly shorter in group P than in group C [20.8 and 10.5
      min vs 44.3 and 19.7 min, respectively (P < 1 x 10(-5))]. CONCLUSIONS: We found
      that the use of EC2 paste in scalp electrode attachment is less time consuming,
      with better recording quality as a result of lower electrode impedance values,
      than the use of collodion. SIGNIFICANCE: EC2 paste may substitute collodion in
      electrode placement for long-term video-EEG monitoring, with an optimal cost
      benefit ratio in terms of recording performance, time consumption, and safety.

PMID- 15982927
TI  - Mismatch responses related to temporal discrimination of somatosensory
      stimulation.
AB  - OBJECTIVE: To determine the existence of a pre-attentively evoked somatosensory
      mismatch negativity component and to investigate the use of that component in
      objective clinical diagnostics. METHODS: First we determined the temporal
      discrimination threshold (DT) of paired stimuli in each subject, and applied two
      sequential electrical stimuli to the hand with paired stimulus times of (1) DT-10
      ms, (2) DT-30 ms and (3) DT+50 ms. Then, we recorded ERPs using an oddball
      paradigm, frequent (standard) and rare (deviant). We used two stimuli, DT-30 ms
      and DT-10 ms, in the first experiment, and DT-30 ms and DT+50 ms, in the second
      experiment. RESULTS: In each experiment, two specific components, a negative
      component peaking at approximately 60ms (N60) and a large positive component
      peaking around 100-200 ms (P150), were identified, mainly following the deviant
      stimulus, which were considered somatosensory mismatch components. N60 was more
      remarkably identified in the second experiment and P150 in the first.
      CONCLUSIONS: N60 might be generated during tasks which subjects can clearly
      discriminate, but P150, which seems to correspond to auditory mismatch
      negativity, might be generated in tasks which require fine discrimination.
      SIGNIFICANCE: We confirmed that our new method could be used for the objective
      examination of temporal discrimination.

PMID- 15982928
TI  - Atypical shoulder muscle activation in multidirectional instability.
AB  - OBJECTIVE: Surface and intramuscular electromyography was used to investigate
      shoulder muscle activity in subjects with multidirectional instability (MDI).
      METHODS: Subjects (seven MDI, 11 control) performed repetitive shoulder
      abduction/adduction, flexion/extension and internal/external rotation movements
      on an isokinetic dynamometer. The activity of the deltoid, infraspinatus,
      supraspinatus, latissimus dorsi, and pectoralis major muscles were recorded using
      double-differential surface and intramuscular fine-wire electrodes. A repeated
      measures analysis of variance evaluated group differences in the amplitude,
      onset, termination and duration of the muscle activity. RESULTS: Significant
      activation parameter differences for the supraspinatus, infraspinatus, posterior
      deltoid and pectoralis major muscles were found in the subjects with MDI. The
      rotator cuff and posterior deltoid muscles demonstrated abbreviated periods of
      activity when performing internal/external rotation, despite activation
      amplitudes that were similar to the controls. In contrast, the activation of the
      pectoralis major differed from the control group in both the amplitude and time
      domains when performing shoulder extension. CONCLUSIONS: MDI is associated with
      atypical patterns of muscle activity that occur even when highly constrained
      movements are used to elicit the activity. SIGNIFICANCE: In addition to
      glenohumeral hyperlaxity, the results suggest that dysfunctional neuromuscular
      control of the rotator cuff is also a contributing factor to the pathoetiology of
      MDI.

PMID- 15982929
TI  - Giardia and Cryptosporidium in mammalian wildlife--current status and future
      needs.
AB  - Environmental pollution with human and domestic-animal fecal material is
      recognized as a potential pathogen pathway for wildlife infections with
      zooanthropomorphic protozoan parasites such as Giardia and Cryptosporidium. In
      this article, we review current knowledge about the diversity of free-living and
      captive terrestrial and marine mammalian wildlife species infected with Giardia
      and Cryptosporidium. The combination of prevalence studies with modern molecular
      genotyping techniques is providing valuable insights into the host specificity
      and possible transmission routes of these two important parasites.

PMID- 15982930
TI  - Thalidomide inhibits growth of tumors through COX-2 degradation independent of
      antiangiogenesis.
AB  - Thalidomide is an antiangiogenic drug and is clinically useful in a number of
      cancers. However, the molecular mechanism by which thalidomide exerts its
      antitumor effects is poorly understood. This study was designed to clarify the
      relationship between antiangiogenesis and antitumor effects of thalidomide and to
      explore the molecular mechanism for its antitumor activity. We evaluated the
      effects of thalidomide on the growth of human tumor cells expressing (MCF-7 and
      HL-60) or not expressing (HeLa and K562) COX-2 in vitro. We also studied the
      effects of thalidomide on COX-1, COX-2 or bcl-2 expression, TNFalpha, VEGF, GSH
      and cytochrome c in these cells. Thalidomide could inhibit tumor growth in a
      concentration-dependent manner in MCF-7 and HL-60; its IC50s for them were
      18.36+/-2.34 and 22.14+/-2.15 microM, respectively, while this effect was not
      observed in HeLa and K562. Thalidomide reduced COX-2 expression accompanied by a
      decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but
      had no effect on that of COX-1, in MCF-7 and HL-60. Moreover, cells not
      expressing COX-2 were insensitive to the growth-inhibitory and effects on
      cytokines of thalidomide. In our mouse xenograft model of OVCAR-3 and HCT-8, we
      found that thalidomide could decrease intratumoral microvessel density in both
      tumors; it exerted antitumor effects only on OVCAR-3 expressing COX-2 but did not
      on HCT-8 not expressing COX-2. Effect of thalidomide on COX-1 and COX-2 in vivo
      was consistent with that of in vitro. These results demonstrated that thalidomide
      might inhibit growth of tumors through COX-2 degradation independent of
      antiangiogenesis.

PMID- 15982931
TI  - Gradual genome stabilisation by progressive reduction of the Saccharomyces uvarum
      genome in an interspecific hybrid with Saccharomyces cerevisiae.
AB  - Considerable amounts of molecular and genetic data indicate that interspecific
      hybridisation may not be rare among natural strains of Saccharomyces sensu
      stricto. Although a post-zygotic barrier operating during meiosis usually
      prevents the production of viable spores, stable hybrids can arise which can even
      evolve into distinct species. This study was aimed to analyse the genome of a
      fertile Saccharomyces cerevisiae x S. uvarum hybrid and monitor its changes over
      four filial generations of viable spores. The molecular genetic analysis
      demonstrated that the two species did not contribute equally to the formation and
      stabilisation of the hybrid genome. S. cerevisiae provided the mitochondrial DNA
      and the more stable part of the nuclear genome. The S. uvarum part of the hybrid
      nuclear genome became progressively smaller by loosing complete chromosomes and
      genetic markers in the course of successive meiotic divisions. Certain S. uvarum
      chromosomes were eliminated and/or underwent rearrangements in interactions with
      S. cerevisiae chromosomes. Numerous S. uvarum chromosomes acquired S. cerevisiae
      telomere sequences. The gradual elimination of large parts of the S. uvarum
      genome was associated with a progressive increase of sporulation efficiency. We
      hypothesise that this sort of genomic alterations may contribute to speciation in
      Saccharomyces sensu stricto.

PMID- 15982932
TI  - Metabolic aspects of aspirin-induced apoptosis in yeast.
AB  - We have previously shown that aspirin induces apoptosis in manganese superoxide
      dismutase (MnSOD)-deficient Saccharomyces cerevisiae cells cultivated in ethanol
      medium, and that it exhibits a significant antioxidant effect until the onset of
      overt apoptosis. We here report that glucose-6-phosphate dehydrogenase activity
      in these cells is not inhibited by aspirin. However, the reducing power, as
      measured by the NADPH/NADP(+) concentration ratio, is significantly lower than in
      wild-type cells. With aspirin, the levels of NADPH, NADP(+) and catalase in MnSOD
      deficient cells decrease significantly after 72 h of cultivation, without
      significant decrease of the NADPH/NADP(+) ratio. This ratio is higher when the
      cells are grown in glycerol or acetate medium. This seems to prevent loss in
      viability and induction of apoptosis on treatment with aspirin. Additionally, the
      glutathione (GSH) level is maintained, but the level of oxidized glutathione
      (GSSG) increases, leading to a significant decrease in the GSH/GSSG ratio in
      aspirin-treated cells. This decrease in the GSH/GSSG ratio is much less in cells
      grown in glycerol medium, while there is an increase in the GSH/GSSG ratio of
      cells grown in acetate medium. Consequently, the decreased reducing power may be
      linked to apoptotic induction by aspirin. This occurs independently of the level
      of reactive oxygen species which, as shown in our previous studies, do not play a
      primary role in the apoptosis of cells exposed to aspirin. The protective effect
      of MnSOD appears to be related to the cellular reducing power.

PMID- 15982933
TI  - Nitric oxide in cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterized by chronic airway infection and
      inflammation, which accounts for most morbidity and deaths. Exhaled nitric oxide
      (NO), elevated in most inflammatory lung diseases, is decreased in CF, suggesting
      decreased formation, increased metabolism or loss of NO. The nitrogen oxide
      metabolism in CF airways is complex and not yet fully understood. In this article
      we will summarize current understanding of the origin and function of NO in
      (patho)physiological processes in the lung of normal subjects and CF patients,
      possible explanations for and consequences of reduced NO concentrations in CF and
      possible therapetic strategies for treatment of CF patients.

PMID- 15982934
TI  - Mealtime behaviors in families of infants and toddlers with cystic fibrosis.
AB  - BACKGROUND: Parents of infants and toddlers with cystic fibrosis (CF) report
      problematic mealtime behaviors. Controlled studies that examine parent and child
      mealtime behaviors in infants and toddlers with CF using objective, observational
      procedures are needed to augment parent report findings and identify targets for
      effective interventions. We examined four hypotheses: 1) Parents of young
      children with CF would engage in more mealtime management behaviors to encourage
      eating than parents of control children. 2) Infants and toddlers with CF would
      engage in more problematic mealtime behaviors than control children. 3) Infants
      and toddlers with CF and their parents would demonstrate a greater frequency of
      behaviors incompatible with eating in the second half of the meal compared to the
      first half. 4) During slow meals, infants and toddlers would display a higher
      rate of mealtime behavior problems than during fast meals. METHODS: Thirty-four
      infants and toddlers with CF (M age = 18.3 +/- 7.9 months) and a matched
      community sample of same age peers participated. Videotaped mealtimes were coded
      using the Dyadic Interaction Nomenclature for Eating (DINE). RESULTS: Parents of
      children with CF gave a higher rate and frequency of commands to eat than
      controls. All children displayed similar rates and frequencies of mealtime
      behaviors incompatible with eating. As the meal progressed, all children,
      regardless of illness status, displayed a greater frequency of behaviors
      incompatible with eating. CONCLUSION: Direct observation of mealtime behaviors
      indicates that parents of infants and toddlers with CF engage in more mealtime
      management behaviors than parents of controls and that young children exhibit
      more behaviors incompatible with eating as the meal progresses. These findings
      highlight modifiable targets for behavioral and nutrition interventions that can
      be specifically designed for families of infants and toddlers with CF.

PMID- 15982935
TI  - Application of superparamagnetic nanoparticles in purification of plasmid DNA
      from bacterial cells.
AB  - The aim of this study was to develop a simple and rapid method for purification
      of ultrapure supercoiled plasmid DNA with high yields from bacterial cultures.
      Nanosized superparamagnetic nanoparticles (Fe3O4) were prepared by chemical
      precipitation method using Fe2+, Fe3+ salt, and ammonium hydroxide under a
      nitrogen atmosphere. The surface of Fe3O4 nanoparticles was modified by coating
      with the multivalent cationic agent, polyethylenimine (PEI). The nanoparticles
      were characterized by transmission electron microscopy, X-ray diffraction,
      Fourier transformation infrared spectroscopy and superconducting quantum
      interference device magnetometer. The PEI-modified magnetic nanobeads were
      employed to simplify the purification of plasmid DNA from bacterial cells. We
      demonstrated a useful plasmid, pRSETB-EGFP, encoding the green fluorescent
      protein with T7 promoter, was amplified in DE3 strain of Escherichia coli. The
      loaded nanobeads are recovered by magnetically driven separation and regenerated
      by exposure to the elution buffer with optimal ionic strength (1.25 M) and pH
      (9.0). Up to approximately 35 microg of high-purity (A260/A280 ratio=1.87)
      plasmid DNA was isolated from 3ml of overnight bacterial culture. EGFP expression
      was detected by fluorescent microscopy in the transformed E. coli cells,
      indicating the biological activities of DNA fragments were retained after
      purified from magnetic nanobeads. The protocol, starting from the preparation of
      bacterial lysate and ending with purified plasmids takes less than 10 min. Thus,
      the separation and purification qualities of PEI-modified magnetic nanobeads as
      well as its ease of use surpass those of conventional anion-exchange resins.

PMID- 15982946
TI  - Siblings' premarital childbearing and the timing of first sex in three major
      cities of Cote d'Ivoire.
AB  - CONTEXT: The association between youths' sexual and reproductive attitudes and
      behaviors and those of their peers and parents has been documented; however,
      information on siblings' influence is scarce, especially for developing
      countries. METHODS: Data on 1,395 female and 1,242 male survey respondents aged
      15-24 from three cities in Cote d'Ivoire were analyzed. Life-table analysis was
      conducted to examine respondents' probability of remaining sexually inexperienced
      according to siblings' history of premarital childbearing. Cox multivariate
      regressions were used to estimate respondents' relative risks of sexual debut by
      age 17 and by age 24. RESULTS: At any age between 15 and 24 years, the life-table
      probability of remaining sexually inexperienced was typically lower among persons
      who had at least one sibling with a premarital birth than among those who had no
      such sibling. In general, among those with at least one sibling who had had a
      premarital birth, the probability was lower if the sibling or siblings and the
      respondent were of the same gender rather than opposite genders, and the
      probability was lowest among those who had a brother and a sister with a history
      of premarital childbearing. In the multivariate analysis for males, having one or
      more brothers only, or having at least one brother and at least one sister, with
      a history of premarital childbearing was associated with increased relative risks
      of being sexually experienced by ages 17 and 24. No such association was found
      for females. CONCLUSION: Programs that seek to reduce premarital sexual activity
      among young people should develop strategies that take into account the potential
      influence of siblings.

PMID- 15982947
TI  - The potential of comprehensive sex education in China: findings from suburban
      Shanghai.
AB  - CONTEXT: More and more Chinese adolescents are engaging in premarital sexual
      activity. As a result, the numbers of unplanned pregnancies and sexually
      transmitted infections (STIs) among Chinese young adults have increased markedly.
      METHODS: A comprehensive sex education program, including information on
      abstinence, contraception and healthy sexual behaviors, was carried out in a
      suburb of Shanghai. The program used six methods for providing information and
      services to unmarried 15-24-year-olds over a period of 20 months. Sexual behavior
      surveys were conducted among intervention participants and among controls in a
      comparable town, who did not receive a similar intervention; chi-square tests and
      logistic regression were used to compare the results. RESULTS: Participation in
      the intervention was not associated with delayed sexual initiation, but was
      associated with reduced odds that youth coerced a partner into having sex (odds
      ratio, 0.3) and with increased odds of contraceptive use (6.2) and condom use
      (13.3) during the intervention period. The greater the level of participation,
      the larger the protective effects. Furthermore, the proportion of youth reporting
      pregnancy involvement during the intervention period was significantly lower in
      the intervention group than among controls (19% vs. 26%). CONCLUSION:
      Comprehensive, community-based interventions may be effective in reaching large
      numbers of Chinese youth and in promoting sexual negotiation, contraceptive use,
      and pregnancy and STI/HIV prevention.

PMID- 15982949
TI  - Wealth and extramarital sex among men in Zambia.
AB  - CONTEXT: In Zambia, most people know about sexually transmitted infections (STIs)
      and HIV/AIDS, but this knowledge has not translated into safer sexual practices.
      An estimated 16% of adults are HIV-positive, with the majority having acquired
      the infection through heterosexual contact. It is important to know whether
      characteristics such as wealth are correlated with extramarital sex among men,
      because men who have sex outside of marriage are key agents of heterosexual
      transmission of STIs and HIV. METHODS: Data for analysis came from 1,239 married
      men who participated in the 2001-2002 Zambia Demographic and Health Survey.
      Multivariate analyses were performed to identify factors associated with men's
      extramarital sexual behavior, with a focus on wealth. RESULTS: Overall, 19% of
      married men had had extramarital sex in the year prior to the survey; their mean
      number of partners was 1.3. Of the three proxies for wealth included in the
      multivariate analyses--education, occupation and household wealth index--none
      were associated with extramarital sex. Living in Southern and Western Provinces
      of Zambia was associated with significantly increased odds of extramarital sex
      (2.3 and 3.5, respectively); older age (0.4), older age at first sex (0.6-0.7)
      and living in Northern Province (0.4) were associated with significantly
      decreased odds of sex outside of marriage. CONCLUSIONS: Cultural norms specific
      to regions play an important part in sexual behavior. Socially defined sexual
      behavior patterns can shed light on extramarital sex and the spread of STIs,
      including HIV.

PMID- 15982948
TI  - Reproductive tract infections among young married women in Tamil Nadu, India.
AB  - CONTEXT: Women often suffer silently with reproductive tract infections (RTIs).
      Studies of the prevalence of these infections in South Asia have been hindered by
      low participation rates, and little is known about rates among the youngest
      married women. METHODS: A community-based cross-sectional study of RTIs was
      conducted in 1996-1997 among married women 16-22 years of age in Tamil Nadu,
      India. The women were questioned about symptoms, received pelvic and speculum
      examinations and provided samples for laboratory tests. Qualitative and
      quantitative data on treatment-seeking behavior were collected. RESULTS: Fifty
      three percent of women reported gynecologic symptoms, 38% had laboratory findings
      of RTIs and 14% had clinically diagnosed pelvic inflammatory disease or
      cervicitis. According to laboratory diagnoses, 15% had sexually transmitted
      infections and 28% had endogenous infections. Multivariate analysis found that
      women who worked as agricultural laborers had an elevated likelihood of having a
      sexually transmitted infection (odds ratio, 2.4), as did those married five or
      more years (2.1). Two-thirds of symptomatic women had not sought any treatment;
      the reasons cited were absence of a female provider in the nearby health care
      center, lack of privacy, distance from home, cost and a perception that their
      symptoms were normal. CONCLUSIONS: Young married women in this rural Indian
      community have a high prevalence of RTIs but seldom seek treatment. Education and
      outreach are needed to reduce the stigma, embarrassment and lack of knowledge
      related to RTIs. The low social status of women, especially young women, appears
      to be a significant influence on their low rates of treatment for these
      conditions.

PMID- 15982950
TI  - The unfinished agenda for reproductive health: priorities for the next 10 years.

PMID- 15982951
TI  - Introduction to Reference Sources in the Health Sciences: an interview with Jo
      Anne Boorkman, Jeffrey T. Huber and Fred W. Roper. Interview by Elizabeth Connor.
AB  - Few works serve as solid a framework for the field of health sciences
      librarianship or provide as many insights and detailed knowledge as Introduction
      to Reference Sources in the Health Sciences. Now in its fourth edition, the
      book's editors and contributors represent an impressive range of experience,
      expertise, and subject knowledge appreciated by practicing librarians in a
      variety of settings and by students of health sciences librarianship. Jo Anne
      Boorkman, Jeffrey T. Huber, and Fred W. Roper answered a series of questions
      about the latest edition of this seminal work, and offered opinions about
      reference works, services, and librarians.

PMID- 15982952
TI  - Digital chat reference in health science libraries: challenges in initiating a
      new service.
AB  - Digital reference service adds a valuable new dimension to health science
      reference services, but the road to implementation can present questions that
      require carefully considered decisions. This article incorporates suggestions
      from the published literature, provides tips from interviews with practicing
      academic health science librarians, and reports on data from students'
      exploration of academic health science library Web sites' digital reference
      services. The goal of this study is to provide guidelines to plan new services,
      assess user needs, and select software, and to showcase potential benefits of
      collaboration and proactive and user-friendly marketing. In addition, tips for
      successful operation and evaluation of services are discussed.

PMID- 15982953
TI  - HIV/AIDS reference questions in an AIDS service organization special library.
AB  - Librarians in many venues may anticipate a wide range of reference questions
      related to HIV and AIDS. Information on HIV/ AIDS is now available in medical,
      academic, and public libraries and on the Internet, and ranges from the most
      complex science to the most private disclosures about personal behavior. In this
      article, the 913 reference questions asked between May 2002 and August 2004 in a
      special library in a mid-western community-based AIDS service organization are
      described and analyzed.

PMID- 15982954
TI  - A primer for effective organization of professional conferences.
AB  - The challenge of organizing a successful conference is a tremendous commitment
      requiring extensive preparation and teamwork. It is tempting but dangerous to
      underestimate the details needed to coordinate an outstanding event. Conferences
      follow a natural life cycle from proposal, gaining administrative support,
      planning, implementing, and then finally evaluating outcomes. These guidelines
      identify the tasks and areas of responsibilities required including setting
      objectives, budgeting, selecting a venue, publicity, programming, and working
      with vendors.

PMID- 15982955
TI  - AgeLine: free and valuable database from AARP.
AB  - AgeLine is the definitive source for information related to people over the age
      of 50, and for issues concerned with aging. AgeLine is available free from the
      AARP Web site, and it provides an excellent search engine with many search
      options. AgeLine is also available by paid subscription from major database
      vendors.

PMID- 15982956
TI  - Locating grey literature on communication disorders.
AB  - This article provides an overview of selected Web-based resources containing grey
      literature in the area of communication disorders. It is geared to practitioners,
      researchers, students, and consumers seeking reliable, freely available
      scientific information. Grey (or gray) literature has been defined as "that which
      is produced on all levels of government, academics, business, and industry in
      print and electronic formats, but which is not controlled by commercial
      publishers."1 This paper reviews various general reference sources potentially
      containing grey literature on communication disorders. This review includes
      identification of the methods specialists in this field use to obtain this
      valuable, yet often overlooked, literature. Access points and search tools for
      identifying grey literature on communication disorders are recommended.
      Commercial databases containing grey literature are not included. Conclusions
      presented in this article are considered complementary to traditionally published
      information resources on communication disorders, such as scholarly journals,
      online databases, etc.

PMID- 15982957
TI  - Marketing the hospital library.
AB  - Many librarians do not see themselves as marketers, but marketing is an essential
      role for hospital librarians. Library work involves education, and there are
      parallels between marketing and education as described in this article. It is
      incumbent upon hospital librarians actively to pursue ways of reminding their
      customers about library services. This article reinforces the idea that marketing
      is an element in many of the things that librarians already do, and includes a
      list of suggested marketing strategies intended to remind administrators,
      physicians, and other customers that they have libraries in their organizations.

PMID- 15982958
TI  - Continuing education as a catalyst for inter-professional collaboration.
AB  - Do nurses have access to the tools and resources they need for evidence-based
      practice? Are librarians prepared to work with nurses to provide access to
      appropriate resources and services, and teach the needed information literacy
      skills? The authors work with professional library and nursing organizations to
      present interdisciplinary continuing education to improve the information
      literacy of nurses and the ability of librarians to provide resources and
      services that meet nurses' information needs. This article reviews behavioral and
      practice changes reported by nurses and librarian participants in symposia on
      evidence-based nursing in March 2001 and May 2003.

PMID- 15982961
TI  - Physician involvement in community coalitions to prevent substance abuse.

PMID- 15982962
TI  - Alcohol-related expectancies and assaults among injured drinkers in the emergency
      department setting.
AB  - This study examined the extent to which alcohol-related expectancies were
      associated with assaults among 278 injured drinkers in the emergency department
      setting. Results of logistic regression analyses indicated that patients who were
      male, had high blood alcohol levels and who expected alcohol to make them more
      careless were more likely to report being assaulted. Conversely, among males,
      patients who expected to become more powerful and aggressive when drinking were
      less likely to be assaulted. These findings suggest that helping patients
      understand how expectancies surrounding alcohol use shape drinking and its
      behavioral concomitants may circumvent their risk for future assaults.

PMID- 15982963
TI  - Correlation between ancillary community services with adolescent substance use
      disorders treatment outcome.
AB  - OBJECTIVE: This study explores whether participation in ancillary out-of-program
      services predicts outcomes of adolescents treated for substance use disorders.
      METHOD: Eighty-eight consenting adolescents, 13-18 years of age recruited at an
      outpatient program filled the Teen Treatment Services Review (T-TSR) during eight
      weekly sessions, and at 3-and 9-Month post-treatment. Outcome variables included
      urinalysis and three subscales of the Teen-Addiction Severity Index (T-ASI)
      during Treatment (DT) and at follow-ups. The predictor variable was the number of
      reported Out-of-Program service contact Days (OD). RESULTS: While DT OD did not
      correlate with DT urinalysis, high DT OD days showed a trend toward predicting
      negative 3-month (3-M) urinalysis. By contrast, high 3-M OD days-predicted
      positive 3-M urinalyses as well as high use on all three T-ASI subscales. Out-of
      Program services between 3-and 9-M post-treatment were not correlated with 9-M
      objective or subjective outcomes. CONCLUSION: The more therapeutic services
      received during treatment, the better the short-term outcome. The more
      therapeutic services received post-treatment, however, the poorer the shortterm
      outcome. Use of outside services presented a response rather than a cause of
      substance use.

PMID- 15982964
TI  - Identifying United States substance abuse treatment programs: a test in one mid
      sized city.
AB  - An accurate national listing of substance abuse treatment programs is essential
      for reporting data about the nation's treatment system and the clients entering
      that system. The National Survey of Substance Abuse Treatment Services (NSSATS)
      is thought to provide the most comprehensive list of treatment providers.
      Therefore, we report a partial test of the concurrent validity of the NSSATS in a
      single mid-sized city. Using operational definitions of "substance abuse
      treatment" and "substance abuse treatment programs" derived from prior work by
      the Center for Substance Abuse Treatment; and working within the defined
      geographic boundaries of a single, mid-sized city, we compared the NSSATS list
      with an independently developed compilation of programs from 5 sources: (1) the
      Yellow Pages; (2) the Internet Infospace Directory; (3) a State directory of
      licensed substance abuse treatment services; (4) the Office of Applied Studies
      Directory; (5) the National Master Facility Inventory. With all sources,
      including NSSATS, we identified 96 separate listings that met the operational
      definition of adult treatment within the geographic bounds of the city. The
      NSSATS identified 70 of those 96 programs (73%), the 5-source compilation
      identified a sample of 83 (86%). While these findings from a single city cannot
      be considered a full test of the validity of the NSSATS, the data presented offer
      at least one partial but promising indication that the NSSATS may be a valid
      national listing and may serve as satisfactory national frame.

PMID- 15982965
TI  - References to alcohol consumption and alcoholism in medical records of a general
      hospital of Porto Alegre, Brazil--a comparison between samples with a 20 year
      gap.
AB  - Two samples of inpatients (493 and 158 subjects, respectively) of a large
      teaching hospital, collected using the same methodology and with a 20-year time
      frame, were analyzed aiming at finding information about alcohol consumption,
      abuse or dependence in the subjects' medical charts. Items reviewed were: the
      list of medical problems; hospital intake form; daily nursing review; medical
      anamnesis; pre-surgery records, and discharge forms. Only 54% and 50% of each
      sample, respectively, had some type of reference to alcohol consumption; when
      references were present, they were in most part incomplete, possibly reflecting
      distortions in the process of gathering information about alcohol consumption
      that involves the client and the health professionals. The authors discuss
      potential reasons for this, suggesting that lack of training of medical personnel
      in the identification of alcoholism, as well as prejudice towards its recovery,
      may be some of the underlying causes.

PMID- 15982966
TI  - Cigarette smoking among marijuana users in the United States.
AB  - The vast majority of drug users smoke cigarettes. Most use marijuana and no other
      illicit drug. We analyzed adult responses to the 1997 NHSDA (n = 16,661) to
      explore relationships between marijuana use and cigarette smoking. Multivariate
      analyses controlled for other illicit drug use and other potential covariates.
      Nearly three-quarters of current marijuana users (74%) smoked cigarettes.
      Compared to nonusers, the adjusted odds of being a smoker were 5.43 for current
      marijuana users, 3.58 for past year marijuana users, and 2.02 for former
      marijuana users. Odds for cigarette smoking among current poly-drug users,
      compared to nonusers, were 2.3 to 1. Level of cigarette smoking was directly
      associated with frequency of marijuana use. Nationwide, an estimated 7 million
      adults smoke both substances and are at increased risk for respiratory illnesses
      and mortality. Cigarette smoking is a major co-morbidity of marijuana use and
      smoking cessation should be addressed among marijuana users in addition to their
      other illicit drug involvement.

PMID- 15982967
TI  - The effects of acetaldehyde in vitro on proteasome activities and its potential
      involvement after alcoholization of rats by inhalation of ethanol vapours.
AB  - BACKGROUND/AIMS: Some models of chronic ethanol administration resulted in
      decreased proteasome activities. The mechanisms still remain speculative. In the
      present study, we tested another model of alcoholization with high blood alcohol
      levels (BALs) and high acetaldehyde fluxes as well as the in vitro effect of
      acetaldehyde on proteasome. Methods/ RESULTS: Ethanol vapour chronically inhaled
      by adult Wistar rats up to a specific protocol, can reach high BALs (200 mg/dl)
      with significant circulating acetaldehyde levels. After 4 weeks of ethanol
      intoxication, although cytochrome CYP2E1 was increased, liver lipid peroxidation
      remained unchanged when protein carbonyls augmented selectively for high
      molecular weight with a decrease of the proteasome activities in ethanol rats.
      Several aldehydes inhibit proteasome function; we specifically explored the
      effects of acetaldehyde, the first alcohol metabolite. Adduction of acetaldehyde
      in vitro to cytosolic proteins inhibits proteasome in a dose-dependent manner.
      Acetaldehyde adducted to purified proteasome also exhibits a decrease in its
      activities. Furthermore, an acetaldehyde-adducted protein, i.e. bovine serum
      albumin (BSA) is less degraded than a native BSA by purified proteasome. These
      findings suggest that acetaldehyde, if overproduced, can inhibit proteasome
      activities and reduce the proteolysis of acetaldehyde-adducted proteins.
      CONCLUSIONS: Our study, for the first time, provided the evidence that
      acetaldehyde by itself inhibits proteasome activities. As the chronic inhalation
      model used in this study is not associated with an overt lipid peroxidation, one
      can suggest that high BALs and their subsequent high acetaldehyde fluxes
      contribute to impairment of proteasome function and accumulation of carbonylated
      proteins. This early phenomenon may have relevance in experimental alcohol liver
      disease.

PMID- 15982968
TI  - Concentrations of glycolytic enzymes and other cytosolic proteins in the
      diffusible fraction of a vertebrate muscle proteome.
AB  - We used a novel microvolumetric technique based on protein diffusion to
      characterize the subproteome of muscle that consists of diffusible proteins,
      including those involved in cell metabolism. Muscle fiber segments were
      mechanically demembranated under mineral oil and transferred into drops of
      relaxing solution. After the fiber segment was depleted of diffusible proteins,
      the content of each drop and residual segment was analyzed by one-dimensional
      polyacrylamide gel electrophoresis. Proteins were identified through peptide mass
      fingerprinting and quantified using purified protein standards. Ten of the most
      abundant cytosolic proteins, distinguished by their ability to readily diffuse
      out of the skinned fiber, were glycolytic enzymes whose concentrations ranged
      from 2.6+/-1.0 g liter-1 (phosphoglucose isomerase) to 12.8+/-1.1 g liter-1 fiber
      volume (pyruvate kinase). The concentrations of the other five most abundant
      cytosolic proteins were as follows: glycogen phosphorylase, 6.0+/-2.3 g liter-1;
      phosphoglucose mutase, 2.2+/-0.2 g liter-1; adenylate kinase, 1.6+/-1.3 g liter
      1; phosphocreatine kinase, 6.6+/-2.6 g liter-1; and parvalbumin, 0.7+/-0.4 g
      liter-1. Given the molecular weight and subunit number of each enzyme, the
      combined concentration of the 15 most abundant cytosolic proteins was 82.3 g
      liter-1; the volume fraction was 0.093. The large volume fraction of diffusible
      proteins favors nonspecific interactions and associations, particularly if the
      glycolytic enzymes and diffusible phosphocreatine kinase are restricted to the I
      band as previous studies suggest. The relative molar concentration of glycolytic
      enzymes is roughly consistent with a stoichiometry of 1:2 for enzymes catalyzing
      the hexose and triose sugar reactions, respectively, a stoichiometry that may
      favor metabolic channeling of intermediates during glycolysis. Our results
      indicate that subcellular fractionation of muscle proteins, in which cytosolic
      constituents are distinguished by their ability to diffuse readily from
      demembranated cells, is a promising microvolumetric technique that allows
      conclusions to be drawn about native protein-protein interactions based on
      concentration and stoichiometry.

PMID- 15982969
TI  - Made in Manchester.

PMID- 15982970
TI  - Academic occupational medicine: its role and its future.

PMID- 15982971
TI  - 'Working lives' by John Darwell.

PMID- 15982973
TI  - The reported incidence of work-related ill-health in Scotland (2002-2003).
AB  - BACKGROUND: Although incidence data for work-related ill-health in the UK are
      available, more detailed information for smaller geographical areas has hitherto
      been unpublished. AIMS: To estimate the incidence of work-related ill-health
      reported by clinical specialists in Scotland, 2002-2003. METHODS: THOR (The
      Health and Occupation Reporting network) is a UK wide reporting scheme for work
      related ill-health. In 2002-2003, 241 out of 2162 physicians in THOR were based
      in Scotland. We have summarized the reported cases and calculated incidence rates
      for categories of ill-health by age, gender and industry. The UK Labour Force
      Survey (2002) was used to provide denominator data, with comparisons made between
      rates for Scotland and the rest of the UK. RESULTS: In 2002-2003, 4043 estimated
      cases were reported from Scotland. Mental ill-health was most frequently reported
      (41%); followed by musculoskeletal disorders (31%), skin disorders (16%),
      respiratory disease (10%), hearing disorders (2%) and infection (1%). The
      reported average annual incidence rate per 100,000 employees for all work-related
      ill-health in Scotland was 86.0. The highest reported rate for mental ill-health
      was found for employees in public administration and defence (76.7 per 100,000),
      and health and social work (72.3 per 100,000). The construction industry had the
      highest reported rate of musculoskeletal disorders (41.6 per 100,000), while
      hairdressers appeared at most risk of developing occupational contact dermatitis
      (rate=86.4 per 100,000). CONCLUSIONS: Despite its limitations, THOR has indicated
      types of work-related ill-health and related industries for targeted disease
      prevention in Scotland.

PMID- 15982974
TI  - The incidence of work-related illness in the UK health and social work sector:
      The Health and Occupation Reporting network 2002-2003.
AB  - BACKGROUND: In the United Kingdom, The Health and Occupation Reporting network
      (THOR) collects incidence data on work-related illness. THOR data show that the
      health and social work sector generates a high proportion of case reports. This
      study analyses the most recent data for the health and social work sector, from
      2002 to 2003. METHODS: Cases returned to the Occupational Physicians Reporting
      Activity (OPRA) scheme and three other specialist schemes (Surveillance of
      Occupational Stress and Mental Illness, Musculoskeletal Occupational Surveillance
      Scheme and occupational skin surveillance) were analysed. Estimates of incidence
      rates for stress-related illness, musculoskeletal disorders and skin disease were
      calculated using two denominators. RESULTS: In this period, 23% (11,016/47,437)
      of all estimated cases in THOR were in health and social work sector employees.
      In OPRA, in the health and social work sector, annual average incidence rates per
      100,000 calculated using Labour Force Survey (LFS) data as the denominator were
      51.2 for mental illness, 35.9 for musculoskeletal disorders and 10.4 for skin
      disease; using McDonald's data as the denominator the corresponding rates were
      119.5, 83.7 and 24.3. In the specialist THOR schemes, annual average incidence
      rates per 100,000 using LFS data as the denominator were 18.4 (mental illness),
      6.1 (musculoskeletal disorders) and 15.3 (skin disease). CONCLUSIONS: Our results
      highlight the importance of collecting information on incident cases and
      denominators, to allow calculation of occupational disease rates. The higher
      incidence of mental illness (compared with musculoskeletal and skin disorders) in
      this employment sector merits further investigation.

PMID- 15982975
TI  - A study of work-related musculoskeletal case reports to The Health and Occupation
      Reporting network (THOR) from 2002 to 2003.
AB  - BACKGROUND: Occupational musculoskeletal disorders are frequently seen by
      occupational physicians and rheumatologists, and there are well-established UK
      based schemes set-up for reporting these conditions. An apparent fall in case
      reporting for work-related musculoskeletal disorders in Great Britain to The
      Health and Occupation Reporting network (THOR) was observed from 2002 to 2003.
      AIMS: To investigate changes in case reporting for musculoskeletal disorders sent
      by occupational physicians to Occupational Physicians Reporting Activity (OPRA)
      and by rheumatologists to Musculoskeletal Occupational Surveillance Scheme (MOSS)
      between 2002 and 2003. METHODS: Musculoskeletal cases returned by more than 800
      physicians from Great Britain reporting to OPRA and MOSS in 2002-2003 were
      analysed. Changes in reporting are described at individual physician and group
      levels in: numbers of participants, levels of response, and numbers of case
      reports by disease category and major occupational and industrial groups.
      RESULTS: In 2002-2003, musculoskeletal disease was the most frequently reported
      major disease category in OPRA. Between 2002 and 2003, the proportion of
      musculoskeletal case reporting fell by 37% in OPRA, and 7% in MOSS. This fall was
      seen in many disease categories, across a wide range of occupations and
      industries. In OPRA, the greatest fall in reporting (74%) was for the category
      Raynaud's/Hand-Arm Vibration Syndrome/Vibration White Finger. CONCLUSIONS: The
      fall in occupational musculoskeletal case reporting between 2002 and 2003 cannot
      be explained by internal factors within the reporting system. This observation
      highlights the need for systematic investigation of trends in case reporting for
      work-related ill-health.

PMID- 15982976
TI  - Work-related infectious disease reported to the Occupational Disease Intelligence
      Network and The Health and Occupation Reporting network in the UK (2000-2003).
AB  - BACKGROUND: Infectious diseases remain an important cause of self-reported work
      related illness, with socio-economic consequences, including sickness absence.
      Reporting of infectious disease by occupational and specialist physicians is an
      important tool in the investigation of occupationally related infections and is
      relevant in their management. AIMS: To examine the reporting of cases of
      infectious disease by occupational and specialist physicians to schemes
      collecting data on occupational ill-health. METHODS: Cases of infectious disease
      reported by occupational and specialist physicians to the UK based schemes,
      Occupational Disease Intelligence Network (ODIN) and The Health and Occupation
      Reporting network (THOR), from 2000 to 2003 were analysed by reporting patterns,
      diagnosis, single case or outbreak reporting and industry. RESULTS: The total
      number of estimated cases of infectious disease reported to ODIN and THOR from
      2000 to 2003 was 5606; 74.9% cases were diarrhoeal disease, and 11.1% scabies.
      The majority (81.4%) of cases were reported in SIDAW, where the participation
      rate for reporters was 55%. Reporting rates were much higher in OPRA, SWORD and
      EPIDERM (ranging from 86 to 96%). The most frequently reported industrial sectors
      were social care (39.5%) and health (29.4%); while the manufacture of chemical
      products contributed 4.3% overall, but 33.8% to estimated cases in OPRA.
      CONCLUSIONS: Despite limitations related to under reporting, the occupational and
      specialist physician schemes in ODIN and THOR provide data that may be used to
      look at patterns of case reporting for occupational ill-health, including
      infectious disease. The reporting schemes also provide an important means of
      alerting peers about potential novel causes, precipitating factors, or industrial
      sectors associated with occupational disease.

PMID- 15982977
TI  - Paraoxonase polymorphisms and self-reported chronic ill-health in farmers dipping
      sheep.
AB  - BACKGROUND: Serum paraoxonase (PON1) provides protection against organophosphate
      induced toxicity. Recently we reported that the frequency of paraoxonase
      polymorphisms in sheep dippers with self-reported chronic ill-health differed
      from that in dippers with a similar dipping history but no ill-health. As these
      analyses may have included subjects with conditions unrelated to organophosphate
      exposure, the aim of this study was to examine whether the risk associated with
      PON1 polymorphisms varied using a more homogenous case and referent population.
      METHODS: Each subject completed a detailed symptom questionnaire and their
      general practitioner was asked whether there was any history of neurological
      disease that could be confused with the effects of organophosphate poisoning.
      Subjects were then excluded both on clinical grounds and where identified as
      atypical on discriminant analysis. RESULTS: Risk associated with the PON1 192 and
      55 genotypes altered little with these changes in the population. CONCLUSIONS:
      These findings are consistent with the hypothesis that organophosphates
      contribute to the self-reported ill-health of sheep dippers.

PMID- 15982978
TI  - Falls and fractures in women at work.
AB  - BACKGROUND: Older women have been observed to have more serious injury
      particularly fractures after slips, trips or falls at the workplace. It is
      unclear whether this excess reflects a greater likelihood of falling or a greater
      proportion presenting with fractures once the fall has occurred. METHODS: Two
      studies were carried out: Study A, of 130 women who fell at work and matched
      referents, and Study B, of 120 women who fell at work and sustained a major
      fracture and 314 matched referents who fell but for whom no fracture was
      recorded. In Study A, the workplace of the case and referent was observed,
      questionnaires completed and objective health measures carried out. Study B
      relied on information obtained from the subject by postal questionnaire. RESULTS:
      Women who fell were older than referents matched on workplace and occupation, but
      age did not continue to be a significant factor after allowing for bodyweight and
      use of spectacles. Fractures were more common in older women who fell,
      particularly post-menopausal women with low body mass. The risk of fracture
      increased steadily with age without an obvious discontinuity around the likely
      age of menopause. CONCLUSIONS: The observed excess of fractures in older women
      falling at work appeared to be explained by the greater risk of fracture among
      those who fell.

PMID- 15982979
TI  - Physicians' beliefs in the assessment of work attribution when reporting
      musculoskeletal disorders.
AB  - BACKGROUND: There is considerable uncertainty about work-relatedness and
      musculoskeletal disorders in general, and it is also not clear how physicians
      decide whether work has caused a disorder in an individual patient. AIMS: To
      investigate physicians' beliefs about assessment of occupational attribution for
      work-related musculoskeletal disorders. METHODS: A questionnaire survey was sent
      to 526 occupational physicians and 248 rheumatologists on: characteristics of
      cases seen, assessment of work attribution, definition of work-relatedness and
      threshold for case reporting. Continuous variables were analysed by mean,
      standard deviation, an independent two-sample t-test and the Mann-Whitney test.
      Mean and median values were calculated and Spearman's rank test was applied to
      ranked data. RESULTS: Questionnaires were completed by 68% occupational
      physicians and 64% rheumatologists. Both groups of physicians believed that
      'history of onset in relation to workplace changes' and 'symptoms consistent with
      work exposure' were the most important factors suggesting work attribution. They
      considered that the most important objective of a reporting scheme was detection
      of trends in disease incidence and that the most suitable criteria for defining
      work-relatedness was the probability that exposure at work 'more likely than not'
      caused the condition (mean 0.73; SD=0.17), in a perceived likelihood scale (0-1).
      CONCLUSION: There was a strong agreement between occupational physicians and
      rheumatologists on questions about work-relatedness and musculoskeletal
      disorders. The level of probability for concluding work-relatedness has been
      quantified.

PMID- 15982980
TI  - The Occupational Medicine agenda: routes and standards of specialization in
      Occupational Medicine in Europe.
AB  - BACKGROUND: This paper reports on the nature of specialist training in
      occupational medicine (OM) in Europe from a survey of representatives from the
      Occupational Medicine section of the European Union of Medical Specialists/Union
      Europeenne des Medecins Specialistes (UEMS). AIMS: To analyse current differences
      existing in the education and training requirements to become a specialist in OM
      in UEMS countries. METHODS: Cross-sectional survey of representatives from 14
      European countries. RESULTS: While undergraduate training duration varied
      slightly, there is marked variation in postgraduate training for OM in UEMS
      countries. The countries surveyed outlined concerns for the funding of training,
      continuing professional development, research requirements and recruitment to the
      specialty. CONCLUSION: There is a marked variation in postgraduate training in OM
      throughout UEMS countries. The variation between postgraduate training programmes
      is not consistent with UEMS charter requirements and because of national
      regulation purposes presents a barrier to the movement of migrant professionals
      within Europe. This study serves as a focus for further research into training
      routes and standards of specialization in OM in Europe.

PMID- 15982981
TI  - Preference of distance learning methods among post-graduate occupational
      physicians and hygienists.
AB  - BACKGROUND: The Centre for Occupational and Environmental Health at the
      University of Manchester has successfully run distance-learning courses for a
      number of decades. These are based on hundreds of pages of (paper-based) written
      text, specially commissioned, packaged and distributed in eight binders.
      Converting printed text to an online format has the potential to improve learning
      through the benefits of information and communication technology as well as to
      save printing and distribution costs. AIM: To determine which distance learning
      method is preferred by postgraduate occupational health students: paper-based
      text, or online text with embedded interactive questions and separate practical
      exercises. METHODS: From approximately 50 paper-based textual course sub-units,
      one was converted to an online format, incorporating a variety of interactive
      text and supplemental practical exercises. Occupational medicine and hygiene
      students were provided with both the paper-based and online versions and asked,
      via anonymous postal questionnaire, a series of questions, including their
      preference for future course sub-units. RESULTS: Sixty-two replies were received
      from 91 registered students (68% response). Apart from one student who had never
      tried the internet, all others described themselves as 'frequent' or 'occasional'
      internet users, with 78% having access both at home and work. Opinion was
      overwhelmingly positive with regard to ease of navigation, quality of the
      interactive exercises and online photo quality. Students tended to prefer
      multiple-choice questions and photo exercises and disliked interactive functions
      asking for words to complete paragraphs. Regarding preference for future teaching
      sub-units, the majority of students answering this question (67%) expressed a
      desire for mostly paper-based text supplemented with interactive online
      exercises. CONCLUSION: Currently enrolled students prefer core teaching materials
      to remain in the printed medium, with the addition of online practical exercises
      to supplement learning.

PMID- 15982982
TI  - The Distance Learning Courses in Occupational Medicine--20 years and onwards.
AB  - BACKGROUND: The first Distance Learning Course in Occupational Medicine was set
      up in 1984 at the Department of Occupational Health, University of Manchester.
      AIMS: This paper describes the progress of that course and developments within
      distance learning education in occupational health at The University of
      Manchester over the subsequent 20 years. It also looks at the future objectives
      and modes of teaching of occupational health at Manchester via distance learning.
      METHODS: Analysis has been undertaken of student demographics and matching
      between original forecasts and actual outcomes. RESULTS: Original forecasts of
      student uptake have been surpassed. There are indications of increases in the
      number of female and part-time students, and a corresponding decline in the
      number of general practitioners enrolling on the Advanced course. Response to
      developing circumstances has resulted in the Distance Learning Unit setting up
      additional courses. CONCLUSIONS: The farsightedness of those who predicted the
      need for academic training in occupational health by distance learning has been
      proved correct. Further evolution is essential to maintain and improve the value
      and success of the courses.

PMID- 15982983
TI  - The Manchester Department--professorial vignettes.

PMID- 15982984
TI  - Jewel in a murky firmament: the Diamond Jubilee History of Occupational Health at
      the University of Manchester.

PMID- 15982985
TI  - It started as a temp: personal memories of the department.

PMID- 15982986
TI  - Foresight brain science, addiction and drugs project.

PMID- 15982987
TI  - Acute hypercarbic gas exposure reveals functionally distinct subpopulations of
      serotonergic neurons in rats.
AB  - Although increasing evidence suggests that anatomically defined subpopulations of
      serotonergic neurons have unique stress-related functional properties, the
      topographical distribution of the serotonergic neurons involved in responses to
      stress-related stimuli have not been well-defined. Inspiration of air containing
      elevated concentrations of carbon dioxide (CO(2); hypercarbic gas exposure) at
      high concentrations activates both hypothalamic-pituitary-adrenal axis and
      sympathetic responses in rats and humans. In order to determine the effects of
      acute hypercarbic gas exposure on subpopulations of topographically organized
      serotonergic neurons, conscious adult male rats were placed in flow cages and
      exposed to either atmospheric air or increasing environmental CO2 concentrations
      (from baseline concentrations up to 20% CO2) for 5min. The presence of
      immunoreactivity for the protein product of the immediate-early gene c-fos was
      used as a measure, at the single cell level, of functional cellular responses
      within subpopulations of serotonergic, noradrenergic and adrenergic neurons. Rats
      exposed to hypercarbic gas had increased numbers of c-Fos/tryptophan hydroxylase
      immunoreactive (ir) and c-Fos/tyrosine hydroxylase-ir neurons in specific
      topographically organized subdivisions of brainstem nuclei, compared to control
      rats. Within serotonergic cell groups (B1-B9), the most striking effects occurred
      in a subpopulation of large, multipolar serotonergic neurons within the
      ventrolateral periaqueductal grey and ventrolateral part of the dorsal raphe
      nucleus, a region implicated in serotonin-dependent suppression of stress-induced
      sympathetic outflow and serotonin-dependent inhibition of 'fight or flight'
      behaviour. These findings have important implications for understanding the role
      of serotonergic systems in the modulation of stress-related physiology and
      behaviour and stress-related neuropsychiatric disorders.

PMID- 15982989
TI  - Diazepam suppresses the acquisition but not the expression of 'fear-potentiation'
      of the acoustic startle response in man.
AB  - Sudden auditory stimuli elicit a short-latency muscular response (acoustic
      startle response) which is enhanced during presentation of a Pavlovian
      conditioned stimulus (CS) that has previously been paired with an aversive
      unconditioned stimulus (US) ('fear-potentiation'). In rodents, acute treatment
      with benzodiazepines blocks both the acquisition of fear-potentiation and the
      expression of fear-potentiation induced by prior exposure to CS/US pairing. We
      examined the effect of diazepam on the acquisition and expression of fear
      potentiation of the acoustic startle response in man. Forty-six male volunteers
      (18-30 years) participated in two sessions separated by 7 days. In session 1,
      they were exposed to 20 2-s presentations of a light (CS), 50% of which
      terminated with an electric shock to the wrist (1.8 mA, 50 ms: US). Somatosensory
      potentials evoked by the US were recorded from the scalp at Cz, and skin
      conductance responses from electrodes taped to the second and fourth fingers. In
      session 2, the CS was presented 20 times without the US; a random 50% of CS
      presentations terminated with a sound pulse (40-ms 115-dB 1-kHz); an equal number
      of sound pulses was presented without the CS. Electromyographic responses of the
      orbicularis oculi muscle to the acoustic stimuli were recorded from electrodes
      placed on the lower eyelid, late-latency auditory evoked potentials were recorded
      at Cz, and skin conductance responses from electrodes taped to the second and
      fourth fingers. In each session, alertness was measured using visual analogue
      self-rating scales and critical flicker fusion frequency. Subjects received
      placebo or diazepam 10mg in the two sessions in a double-blind protocol: group 1
      (n 12) placebo/placebo; group 2 (n 11) placebo/diazepam; group 3 (n 12)
      diazepam/placebo; group 4 (n 11) diazepam/diazepam. Diazepam reduced alertness as
      measured by visual-analogue self-rating scales and critical flicker fusion
      frequency. In session 1, diazepam reduced the amplitude of the somatosensory
      potentials and skin conductance responses evoked by the CS. In session 2, the
      acoustic startle response, the N1/P2 auditory evoked response and the skin
      conductance response evoked by the sound stimuli were enhanced in the presence of
      the CS. This fear-potentiation was attenuated in subjects who received diazepam
      in session 1, but was not affected by the treatment given in session 2. The
      results indicate that diazepam blocks the acquisition of fear-potentiation of
      startle responses in man, as in animals, but does not prevent the expression of a
      previously learned response.

PMID- 15982988
TI  - Cinnarizine has an atypical antipsychotic profile in animal models of psychosis.
AB  - Cinnarizine, a drug known as a calcium channel blocker, is currently used for the
      treatment of migraine and vertigo. Induction of extrapyramidal signs by
      cinnarizine has been reported in the elderly, which is related to its moderate
      antagonistic properties at dopamine D2 receptors, resembling the mechanism of
      action of most antipsychotic drugs. Despite this effect, cinnarizine has never
      been tested as a putative antipsychotic drug. Here we evaluate the potential
      effect of cinnarizine in two pharmacological models of psychosis, namely
      amphetamine- and MK-801-induced hyperlocomotion, as well as its ability to induce
      catalepsy. Cinnarizine significantly counteracted MK-801 (0.25 mg/kg) and
      amphetamine (5mg/kg) locomotor effects at doses as low as 20mg/kg, having no
      incremental effect at 60 or 180 mg/kg. Regarding side-effects, cinnarizine
      induced no catalepsy in mice at the effective dose of 20 mg/kg, inducing only
      mild catalepsy at the doses of 60 and 180 mg/kg. Based on these results and on
      the antagonist effect of cinnarizine on dopamine D2 receptors, we suggest that it
      has a potential antipsychotic effect with an atypical profile that should be
      evaluated clinically.

PMID- 15982990
TI  - Single doses of Panax ginseng (G115) reduce blood glucose levels and improve
      cognitive performance during sustained mental activity.
AB  - Single doses of the traditional herbal treatment Panax ginseng have recently been
      shown to elicit cognitive improvements in healthy young volunteers. The
      mechanisms by which ginseng improves cognitive performance are not known.
      However, they may be related to the glycaemic properties of some Panax species.
      Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy
      young adults completed a 10 min test battery at baseline, and then six times in
      immediate succession commencing 60 min after the day's treatment (placebo, 200mg
      G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction
      task (2 min); a Serial Sevens task (2 min); a Rapid Visual Information Processing
      task (5 min); then a 'mental fatigue' visual analogue scale. Blood glucose was
      measured prior to each day's treatment, and before, during and after the post
      dose completions of the battery. Both the 200mg and 400mg treatments led to
      significant reductions in blood glucose levels at all three post-treatment
      measurements (p 0.005 in all cases). The most notable behavioural effects were
      associated with 200mg of ginseng and included significantly improved Serial
      Sevens subtraction task performance and significantly reduced subjective mental
      fatigue throughout all (with the exception of one time point in each case) of the
      post-dose completions of the 10 min battery (p 0.05). Overall these data suggest
      that Panax ginseng can improve performance and subjective feelings of mental
      fatigue during sustained mental activity. This effect may be related to the acute
      gluco-regulatory properties of the extract.

PMID- 15982991
TI  - MDMA affects both error-rate dependent and independent aspects of decision-making
      in a two-choice prediction task.
AB  - Decision-making, i.e. selecting an action from a number of alternatives when the
      outcome is uncertain, is a complex process that is important for everyday life.
      3,4-Methylenedioxymethamphetamine (MDMA), also known as 'Ecstasy', is a widely
      used recreational drug that is known to increase serotonin (5-HT) and, to a
      lesser extent, dopamine (DA) in animals. This study examined whether MDMA alters
      decision-making in a way that depends on the degree of success and outcome.Forty
      two normal, healthy volunteers were given placebo or 1.5mg/kg p.o. MDMA in a
      randomized crossover design. Subjects completed the two-choice prediction task
      120min after administration of the drug. Decision-making characteristics were
      obtained at 20% error rate, 50% error rate or 80% error rate.MDMA affected
      decision-making via a process that is dependent on success or failure.
      Administration of MDMA increased the degree to which the previous response
      predicted the current response (mutual information) and the average response
      sequence predictability (average dynamical entropy) at low error rates. MDMA
      increased the degree to which the previous stimulus influenced the selection of
      the current response at 20%, 50% or 80% error rate. MDMA did not significantly
      alter basic response characteristics such as response latency or switching. Self
      assessment of the psychological state induced by MDMA did not predict the MDMA
      induced decision-making patterns. These results support the hypothesis that acute
      administration of MDMA affects success-related response selection during decision
      making.

PMID- 15982992
TI  - Memory function in women with premenstrual complaints and the effect of
      serotonergic stimulation by acute administration of an alpha-lactalbumin protein.
AB  - Serotonergic hypofunction may underlie at least part of the symptoms that are
      experienced by women with premenstrual complaints, including memory deficits. In
      the current study we investigated changes in memory functions in the premenstrual
      phase compared to the early postmenstrual phase in 16 women with premenstrual
      complaints. In addition, the effect of an acute serotonergic stimulation by
      administration of an alpha-lactalbumin protein on premenstrual memory performance
      was assessed using a double-blind placebo-controlled crossover design. It was
      found that both short-term and long-term memory for words (30-word learning task)
      and abstract figures (abstract visual learning task) were mildly impaired in the
      premenstrual phase. Administration of alpha-lactalbumin during the premenstrual
      phase could only partially attenuate the memory performance decrements that are
      seen in the premenstrual phase. Specifically, alphalactalbumin improved long-term
      memory for abstract figures, but not for words. There were no effects of
      menstrual phase or alpha-lactalbumin on planning functions (computerized Tower of
      London). The data suggest that serotonergic hypofunction may play a role in
      premenstrual memory decline, but serotonergic mechanisms cannot fully account for
      observed cognitive changes in the premenstrual phase.

PMID- 15982993
TI  - Heterogeneity of serum tryptophan concentration and availability to the brain in
      patients with the chronic fatigue syndrome.
AB  - We assessed the serotonin status of patients with the chronic fatigue syndrome
      (CFS). Tryptophan (Trp) availability to the brain, expressed as the ratio of
      concentration of serum Trp to the sum of those of its five competitors (CAA), and
      other parameters of Trp disposition were compared in 23 patients with the CFS and
      42 healthy controls. The serum [free Trp]/[CAA] ratio was 43% higher in CFS
      patients, due to a 48% higher [free Trp]. [Total Trp] was also significantly
      higher (by 19%) in CFS patients, and, although the [total Trp]/[CAA] ratio did
      not differ significantly between the control and patient groups, the difference
      became significant when the results were co-varied with age and gender. [CAA] was
      not significantly different between groups, but was significantly lower in
      females, compared to males, of the CFS patient group. We have established normal
      ranges for Trp disposition parameters and propose criteria for defining the
      serotonin-biosynthetic status in humans. We have provisionally identified two
      subgroups of CFS patients, one with normal serotonin and the other with a high
      serotonin status. The relevance of our findings to, and their implications for,
      the pharmacological and other therapies of the chronic fatigue syndrome are
      discussed.

PMID- 15982994
TI  - Augmentation strategy with olanzapine in resistant obsessive compulsive disorder:
      an Italian long-term open-label study.
AB  - The present study reports the results of an open-label trial on the use of the
      combination of olanzapine (an atypical antipsychotic) serotonin reuptake
      inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive
      compulsive disorder (OCD). All patients had been suffering from OCD, according to
      DSM IV criteria, for at least 2 years and had different comorbid disorders; they
      had been treated with an SRI at adequate dosages for at least 6 months, or had
      tried different augmentation strategies with no or poor response. As a result,
      olanzapine was added and continued for 1 year. After 12 weeks of this regimen,
      most of the patients (17) had shown a reduction in OC symptoms, as assessed by a
      decrease in the Yale-Brown Obsessive Compulsive Scale total score, which
      continued throughout subsequent months. Only mild side-effects were recorded and
      no patient halted the treatment. The addition of olanzapine would appear to be a
      useful short- and long-term strategy for augmenting SRI effectiveness in
      resistant OCD patients, especially in those presenting comorbidity with bipolar
      disorders.

PMID- 15982995
TI  - Influence of age and gender on risperidone plasma concentrations.
AB  - There is limited information on gender- and age-specific effects on plasma
      concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone.
      The present study investigated dose- and weight-adjusted plasma concentrations of
      risperidone and its metabolite in three age groups (45 years, 45-60 years, over
      60 years). Gender-specific differences were examined in the whole sample and for
      the premenopausal subgroup. One hundred and twenty-nine patients (18-93 years)
      were included in the study, 52 (40%) male and 77 (60%) female. Concentrations of
      risperidone and 9-hydroxyrisperidone were measured at steady-state by high
      performance liquid chromatography with electrochemical detection (HPLC-ED). When
      total plasma concentrations (risperidone plus 9-hydroxyrisperidone) were adjusted
      for daily maintenance dose (ng/mL/mg C/D ratio), significant differences between
      all age groups were found. We found a mean increase of the C/D ratio by 34.8% per
      decade in patients older than 42 years. No significant sex-related differences in
      the average plasma concentrations were observed for the whole sample and for the
      premenopausal subgroup. This study shows clear evidence of higher risperidone
      total plasma concentrations for patients over 40 years of age. This linear
      increase (over 30% per decade) may then lead to an increased incidence of adverse
      effects in elderly patients.

PMID- 15982996
TI  - A survey of the off-label use of mood stabilizers in a large psychiatric
      hospital.
AB  - The term 'off-label' prescribing refers to the use of a drug outside the terms of
      its Marketing Authorization, including prescribing for an unlicensed indication.
      The aims of the study were to determine the frequency of off-label prescriptions
      for mood stabilizers (lithium and antiepileptics) among inpatients of a large
      psychiatric hospital, the nature of the off-label clinical indications in use and
      whether patients had been informed about the off-label usage.A cross-sectional
      survey of inpatients aged 18-65 years at St Andrew's Hospital, Northampton, UK
      and interviews with consultant psychiatrists about off-label usage of mood
      stabilizers were carried out. Of the 249 patients studied, 75 (30.1%) were
      receiving one or more mood stabilizers, of which 71 (94.7%) were off-label. The
      most frequently cited off-label indications for mood stabilizers were:
      prophylaxis of mood swings (48 cases), treatment of aggression (31), manic
      symptoms (10), antipsychotic augmentation in treatment-resistant schizophrenia
      (7) and post-traumatic stress disorder (6). Lithium was prescribed infrequently.
      The reasons for this are discussed. Although in most instances the psychiatrist
      was aware the drug was being used off-label, in less than one-third of cases had
      the patient been informed of this, partly because of anticipated difficulties in
      their understanding the off-label concept, but also because of concerns that this
      information could adversely affect compliance. The off-label prescription of mood
      stabilizers is very common in psychiatry and such usage benefits patients. When
      prescribing off-label, psychiatrists should consider the evidence that the drug
      is likely to be effective for the unlicensed indication. Where there is limited
      evidence of benefit, a trial of the drug, with clinical monitoring, may be
      indicated. Patients should be fully informed about their medication, and this
      includes information that the prescription is off-label. Pharmacists can assist
      this process. The off-label concept may be difficult for some patients to
      understand.

PMID- 15982997
TI  - The place of partial agonism in psychiatry: recent developments.
AB  - Drugs used to treat psychiatric disorders, although effective, are often
      restricted by adverse events. The use of partial agonists for treating
      hypertension was found to limit some of the side-effects in some patients. This
      led to the investigation of partial agonists as a treatment modality in
      psychiatric disorders. Partial agonists have a lower intrinsic efficacy than full
      agonists leading to reduced maximum response. They can act as antagonists by
      competing for receptor binding with full agonists. The level of activity depends
      on the level of endogenous receptor activity. Buprenorphine, a partial agonist at
      the mu-opioid receptor, is used to treat patients with addiction and decreases
      the symptoms of withdrawal and risks of overdose and intoxication. The anxiolytic
      buspirone shows partial agonism at 5-HT(1A) receptors, and this seems to provide
      anxioselective effects, without inducing extrapyramidal side-effects,
      convulsions, tolerance or withdrawal reactions. In schizophrenia, partial
      dopamine agonism results in antagonistic effects at sites activated by high
      concentrations of dopamine and agonistic effects at sites activated by low
      concentrations of dopamine. This stabilizes the dopamine system to effect
      antipsychotic action without inducing adverse motor or hormonal events.
      Aripiprazole is the first 'dopamine system stabilizer', and the data are
      promising, with efficacy at least equivalent to that with current atypical
      antipsychotics but fewer of the troublesome side-effects. Partial agonists seem
      to provide a way to fine-tune the treatment of psychiatric disorders by
      maximizing the treatment effect while minimizing undesirable adverse events.

PMID- 15982998
TI  - Medicinal plants for insomnia: a review of their pharmacology, efficacy and
      tolerability.
AB  - A number of medicinal plants are traditionally endowed with anxiolytic or
      sedative properties and, in the context of this revue, both indications are
      considered since the former may induce a mood conducive to the latter. For any
      sleep-inducing drug to be effective, a tranquil ambience needs to be established
      a priori. Thus, physical ailments (i.e. pain), factors interfering with sleep
      (i.e. noise), psychological conditions causing stress, psychiatric illnesses
      (i.e. depression) and other drugs that interfere with sleep (i.e. caffeine) need
      to be controlled, if possible. Kava-kava is a well-established hypnotic drug,
      with a rapid onset of effect, adequate duration of action and minimal morning
      after-effects. However, reports of serious hepatotoxicity with this preparation
      have led to it being banned in most countries worldwide. On the other hand, side
      effects with valerian would appear to be bland indeed. However, it's slow onset
      of effect (2-3 weeks) renders it unsuitable for short-term use (i.e. 'jet-lag'),
      but it does have profound beneficial effects on sleep architecture (augments deep
      sleep) that may make it particularly suitable for long-term use and for the
      elderly. In a personal trial (not double-blind) in stress-induced insomnia, both
      kava and valerian improved sleep and the ill-effects of stress, and the
      combination of the two was even more effective for the control of insomnia.
      Aromatherapy (lavender, chamomile, Ylang-Ylang) would appear to improve sleep,
      but how practical a form of treatment this may be remains to be determined. The
      only other plant drug that may have some effect on sleep is melissa, but reports
      are too scanty to form any opinion about this. Based on animal experiments,
      passion flower (passiflora) may have a sedative action, but the sedative action
      of hops has not been investigated in any detail. In conclusion, there is a need
      for longer-term controlled studies with some of these compounds (particularly
      valerian). Aromatherapy constitutes a tantalising possibility. In the
      interpretation of this review, it should be borne in mind that the evidence on
      which it is based is often incomplete or missing, but that is all that is
      available. Consequently some conjecture on the part of the author is inevitable
      and should be appreciated as such.

PMID- 15982999
TI  - Neuroleptic malignant syndrome due to three atypical antipsychotics in a child.
AB  - Neuroleptic Malignant Syndrome (NMS) is a rare, potentially fatal and
      idiosyncratic drug reaction. It is characterized by a sudden loss of body
      temperature control, renal and respiratory failure, muscle rigidity, loss of
      consciousness and impairment of autonomic nervous system. Although NMS was
      previously associated with the use of classical high-potency neuroleptics, cases
      have started to emerge with atypical neuroleptics. This article discusses the
      first case of NMS in a child, induced by the use of risperidone, olanzapine and
      quetiapine.

PMID- 15983000
TI  - Is clonidine useful for treatment of clozapine-induced sialorrhea?
AB  - Clozapine has shown superior efficacy in treatment of refractory schizophrenia,
      but its use is limited by emergent side-effects. Among other adverse effects,
      sialorrhea is a troublesome side-effect, its stigmatizing nature results in poor
      treatment compliance. Several hypotheses have been put forward in the etiology of
      clozapine-induced sialorrhea. 2 adrenergic antagonism is hypothesized to be
      involved in its pathophysiology, based on the response to clonidine and
      lofexidine. Oral clonidine (50 to 100 g/day) was tried on 12 stable outpatients
      of schizophrenia maintained on clozapine. Wet area over the pillow as reported by
      the patients was recorded at baseline and at 4 weeks of treatment along with the
      subjective response after the treatment. Most of the patients reported a decrease
      in sialorrhea without any adverse events. We describe encouraging results in an
      open case series of oral clonidine for clozapine-induced sialorrhea.

PMID- 15983001
TI  - Acute tryptophan or tyrosine depletion test: time for reappraisal?

PMID- 15983003
TI  - Clozapine monotherapy for catatonic schizophrenia: should clozapine be the
      treatment of choice, with catatonia rather than psychosis as the main therapeutic
      index?

PMID- 15983004
TI  - Olanzapine plus venlafaxine in treatment-resistant depression.

PMID- 15983005
TI  - The rising prevalence of treated disease: effects on private health insurance
      spending.
AB  - In this paper we present a new framework for understanding the factors driving
      the growth in private health insurance spending. Our analysis estimates how much
      of the rise in spending is attributable to a rise in treated disease prevalence
      and spending per treated case. Our results reveal that the rise in treated
      disease prevalence, rather than the rise in spending per treated case, was the
      most important determinant of the growth in private insurance spending between
      1987 and 2002. A rise in population risk factors and the introduction of new
      technologies underlie these trends.

PMID- 15983007
TI  - How are leaves plumbed inside a branch? Differences in leaf-to-leaf hydraulic
      sectoriality among six temperate tree species.
AB  - The transport of water, sugar, and nutrients in trees is restricted to specific
      vascular pathways, and thus organs may be relatively isolated from one another
      (i.e. sectored). Strongly sectored leaf-to-leaf pathways have been shown for the
      transport of sugar and signal molecules within a shoot, but not previously for
      water transport. The hydraulic sectoriality of leaf-to-leaf pathways was
      determined for current year shoots of six temperate deciduous tree species (three
      ring-porous: Castanea dentata, Fraxinus americana, and Quercus rubra, and three
      diffuse-porous: Acer saccharum, Betula papyrifera, and Liriodendron tulipifera).
      Hydraulic sectoriality was determined using dye staining and a hydraulic method.
      In the dye method, leaf blades were removed and dye was forced into the most
      proximal petiole. For each petiole the vascular traces that were shared with the
      proximal petiole were counted. For other shoots, measurements were made of the
      leaf-area-specific hydraulic conductivity for the leaf-to-leaf pathways (k(LL)).
      In five out of the six species, patterns of sectoriality reflected phyllotaxy;
      both the sharing of vascular bundles between leaves and k(LL) were higher for
      orthostichous than non-orthostichous leaf pairs. For each species, leaf-to-leaf
      sectoriality was determined as the proportional differences between non
      orthostichous versus orthostichous leaf pairs in their staining of shared
      vascular bundles and in their k(LL); for the six species these two indices of
      sectoriality were strongly correlated (R2=0.94; P <0.002). Species varied 8-fold
      in their k(LL)-based sectoriality, and ring-porous species were more sectored
      than diffuse-porous species. Differential leaf-to-leaf sectoriality has
      implications for species-specific co-ordination of leaf gas exchange and water
      relations within a branch, especially during fluctuations in irradiance and water
      and nutrient availability.

PMID- 15983006
TI  - Generating molecular diversity by homologous recombination in Escherichia coli.
AB  - We explored the use of recE-mediated homologous recombination to generate
      molecular diversity in Escherichia coli. Two homologous genes were placed on
      different phagemid vectors each comprising multiple EcoRI restriction sites and
      overlapping N- and C-terminal portions of beta-lactamase. By co-infection of
      these phage into RecE+ EcoRI+ E.coli, we were able to introduce double-strand
      breaks into these vectors, allowing efficient homologous recombination (in up to
      10% of bacteria) by the recE pathway and selection of the recombinants by
      resistance to ampicillin. Recombination gave single crossovers; these were more
      frequent near the EcoRI sites and the recombination frequency increased with the
      target length and degree of homology. The system was used to create a large
      combinatorial chicken antibody library (10(10)) for display on filamentous phage
      and to isolate several antibody fragments with binding affinities in the 10-100
      nM range.

PMID- 15983008
TI  - A coupled yeast signal sequence trap and transient plant expression strategy to
      identify genes encoding secreted proteins from peach pistils.
AB  - Many developmental processes and induced plant responses have been identified
      that are directly or indirectly influenced by wall-localized, or apoplastic,
      molecular interactions and signalling pathways. The yeast-based signal sequence
      trap (YSST) is a potentially valuable experimental tool to characterize the
      proteome of the wall and apoplast, or 'secretome', although few studies have been
      performed with plants and to date this strategy has not been coupled with a
      subsequent analysis to confirm extracellular localization of candidate proteins
      in planta. This current report describes the use of the YSST, together with
      transient expression of a selection of identified proteins as fusions with the
      reporter GFP, focusing on the complex extracellular interactions between peach
      (Prunus persica) pollen and pistil tissues. The coupled YSST and GFP localization
      assay was also used to confirm the extracellular localization of a recently
      identified pistil-specific basic RNase protein (PA1), as has been observed with S
      RNases that are involved in self-incompatibility. This pilot YSST screen of
      pollinated and unpollinated pistil cDNAs revealed a diverse set of predicted cell
      wall-localized or plasma membrane-bound proteins, several of which have not
      previously been described. Transient GFP-fusion assays and RNA gel blot analyses
      were used to confirm their subcellular localization and to provide further
      insights into their expression or regulation, respectively. These results
      demonstrated that the YSST strategy represents an effective means either to
      confirm the extracellular localization of a specific candidate secreted protein,
      as demonstrated here with PA1, or to conduct a screen for new extracellular
      proteins.

PMID- 15983009
TI  - Tyr152 plays a central role in the catalysis of 1-aminocyclopropane-1-carboxylate
      synthase.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) synthase is a key enzyme in the
      regulation of ethylene biosynthesis in higher plants. To investigate the
      catalytic significances of two conserved tyrosine residues, Tyr151 and Tyr152, of
      a tomato ACC synthase isozyme (LeACS2), five ACC synthase mutants (Y151F, Y151G,
      Y152F, Y152G, and Y151F/Y152F) were constructed and over-expressed in Escherichia
      coli. Subsequent kinetic analysis indicated that these point mutations in mutants
      Y152F, Y152G, and Y151F/Y152F, either reduced the catalytic efficiency more than
      98% or fully inactivated ACC synthase, while Y151F and Y151G mutants reduced the
      enzymatic activities by 27% and 83%, respectively. It is therefore concluded that
      Tyr152, especially its hydroxyl group, plays an essential role in the catalysis
      of ACC synthase. Thus, a revised catalytic model is hereby proposed for
      functional ACC synthase.

PMID- 15983010
TI  - Overexpression of SIPK in tobacco enhances ozone-induced ethylene formation and
      blocks ozone-induced SA accumulation.
AB  - Ozone induces rapid activation of SIPK, a mitogen-activated protein kinase (MAPK)
      in tobacco. Through transgenic manipulation it has previously been shown that
      overexpression of SIPK leads to enhanced ozone-induced lesion formation with
      concomitant accumulation of ROS. In spite of this hypersensitive phenotype, the
      effect of this altered SIPK expression on the levels of various hormones that
      regulate ozone-induced cell death has remained unexplored. The response of both
      salicylate and ethylene, the major phytohormones that modulate ozone-induced cell
      death, have now been analysed in SIPK-OX tobacco plants. Ozone treatment strongly
      induced ethylene formation in the sensitive SIPK-OX plants at ozone
      concentrations that failed to elicit stress ethylene release in WT plants. By
      contrast, SIPK-overexpressing plants displayed no ozone-induced SA accumulation,
      whereas WT plants accumulated SA upon ozone exposure. Epistatic analysis of SIPK
      OX function suggests that the ozone-induced cell death observed in SIPK-OX plants
      is either independent, or upstream, of SA accumulation.

PMID- 15983011
TI  - Involvement of ethylene biosynthesis and perception in the susceptibility of
      citrus fruits to Penicillium digitatum infection and the accumulation of defence
      related mRNAs.
AB  - Citrus fruits infected with the fungus Penicillium digitatum substantially
      increase the production of the plant hormone ethylene. In this study, the
      regulation of ethylene biosynthesis in Citrus sinensis-infected fruits and its
      putative involvement in an active defence response against P. digitatum infection
      is examined. Ethylene production is demonstrated as being the result of the co
      ordinated and differential up-regulation of at least three ethylene biosynthetic
      genes: ACS1, ACS2, and ACO. Blocking ethylene perception by 1-MCP resulted in an
      increased ethylene production and ACS2 expression during infection and mechanical
      wounding, suggesting that this gene is negatively regulated by ethylene. ACO
      expression was induced by ethylene in the absence of wounding or infection,
      although further results indicate that its induction during the course of
      infection may not be primarily mediated by ethylene. Treatment with 1-MCP also
      increased susceptibility to Penicillium decay, showing an involvement of ethylene
      perception in promoting defence responses in citrus fruits. The changes in the
      expression of two defence-related genes up-regulated during infection were also
      studied: the ones coding for phenylalanine ammonia-lyase (PAL) and an acidic
      class II chitinase (ACR311). The onset of PAL expression after mechanical
      wounding or inoculation was not changed in 1-MCP-pretreated fruits, while its
      later increase during the course of infection was abolished. Chitinase gene
      induction was more related to mechanical damage and was partially repressed by
      ethylene. These studies indicate distinct possible regulatory mechanisms of plant
      fruit defence genes in the context of fungal infection and ethylene perception.

PMID- 15983012
TI  - The modulating effect of the perisperm-endosperm envelope on ABA-inhibition of
      seed germination in cucumber.
AB  - Abscisic acid (ABA) markedly reduced the germination of developing seeds at much
      lower concentrations (ABA50=0.1 mM) compared with that of mature seeds (ABA50=1.6
      mM) in cucumber (Cucumis sativus L. cv. Green long). The perisperm-endosperm (PE)
      envelope in developing seeds showed partly differentiated lipid and callose
      layers, considerable ABA biosynthetic activity in endosperm cells, and
      appreciable permeability to applied ABA. The decrease in the sensitivity of seeds
      to applied ABA was coincident with the complete development of lipid and callose
      layers, diminished ABA biosynthetic activity in endosperm cells in imbibed mature
      seeds, and moderate permeability of the PE envelope to applied ABA. Decoated
      seeds pretreated with chloroform showed decreased germination (ABA50=0.4 mM) in
      response to applied ABA and increased ABA permeation through the PE envelope. ABA
      thus allowed to permeate into embryonic tissues substantially reduced the
      pregerminative activity of beta-glucanase in the radicles. The structure and
      biophysical/biochemical properties of the PE envelope seem to modulate the effect
      of ABA on the germination of developing and mature cucumber seeds.

PMID- 15983013
TI  - Impact of deficit irrigation on water use efficiency and carbon isotope
      composition (delta13C) of field-grown grapevines under Mediterranean climate.
AB  - The objective of this study was to evaluate the effect of deficit irrigation on
      intrinsic water use efficiency (A/g(s)) and carbon isotope composition (delta13C)
      of two grapevine cultivars (Moscatel and Castelao), growing in a commercial
      vineyard in SW Portugal. The study was done in two consecutive years (2001 and
      2002). The treatments were full irrigation (FI), corresponding to 100% of crop
      evapotranspiration (ETc), rain-fed (no irrigation, NI), and two types of deficit
      irrigation (50% ETc): (i) by supplying the water either to one side of the root
      system or to the other, which is partial rootzone drying (PRD), or (ii) dividing
      the same amount of water by the two sides of the root system, the normal deficit
      irrigation (DI). The water supplied to the PRD treatment alternated sides
      approximately every 15 d. The values of predawn leaf water potential (Psi(pd))
      and the cumulative integral of Psi(pd) (S(Psi)) during the season were lower in
      2001 than in the 2002 growing season. Whereas differences in Psi(pd) and S(Psi)
      between PRD and DI were not significantly different in 2001, in 2002 (a dryer
      year) both cultivars showed lower values of S(Psi) in the PRD treatment as
      compared with the DI treatment. This suggests that partial rootzone drying may
      have a positive effect on water use under dryer conditions, either as a result of
      better stomatal control and/or reduced vigour. The effects of the water
      treatments on delta13C were more pronounced in whole grape berries and pulp than
      in leaves. The delta13C of pulp showed the best correlation with intrinsic water
      use efficiency (A/g(s)) as well as with S(Psi). In spite of the better water
      status observed in PRD compared with DI in the two cultivars in 2002, no
      statistical differences between the two treatments were observed in A/g(s) and
      delta13C. On the other hand, they showed a higher delta13C compared with FI. In
      conclusion, it is apparent that the response to deficit irrigation varies with
      the environmental conditions of the particular year, the driest conditions
      exacerbating the differences among treatments. The highest values of delta13C
      found in the pulp of NI vines in Castelao compared with Moscatel suggest
      different sensitivities to water deficits in the two cultivars, as was
      empirically observed.

PMID- 15983014
TI  - Physiological characterization of Mg deficiency in Arabidopsis thaliana.
AB  - Although the symptoms of magnesium deficiency are well documented in plants, the
      primary physiological effects of low Mg availability remain largely unknown. This
      paper describes the physiological responses of Mg starvation in Arabidopsis
      thaliana. Growth characteristics, Mg and sugar concentration, and photochemical
      performance were measured at regular intervals during the induction of Mg
      deficiency. These data show that Mg deficiency increased the sugar concentration
      and altered sucrose export from young source leaves before any noticeable effect
      on photosynthetic activity was seen. The decline in photosynthetic activity might
      be elicited by increased leaf sugar concentrations. Transcript levels of Cab2
      (encoding a chlorophyll a/b protein) were lower in Mg-deficient plants before any
      obvious decrease in the chlorophyll concentration. These transcriptional data
      suggest that the reduction of chlorophyll is a response to sugar levels, rather
      than a lack of Mg atoms for chelating chlorophyll.

PMID- 15983015
TI  - The role of ozone flux and antioxidants in the suppression of ozone injury by
      elevated CO2 in soybean.
AB  - The projected rise in atmospheric CO2 concentration is expected to increase
      growth and yield of many agricultural crops. The magnitude of this stimulus will
      partly depend on interactions with other components of the atmosphere such as
      tropospheric O3. Elevated CO2 concentrations often lessen the deleterious effects
      of O3, but the mechanisms responsible for this response have received little
      direct examination. Previous studies have indicated that protection against O3
      injury by elevated CO2 can be attributed to reduced O3 uptake, while other
      studies suggest that CO2 effects on anti-oxidant metabolism might also be
      involved. The aim of this experiment was to test further the roles of O3 flux and
      antioxidant metabolism in the suppression of O3 injury by elevated CO2. In a two
      year experiment, soybean [Glycine max (L.) Merr.] was exposed from emergence to
      maturity to charcoal-filtered air or charcoal-filtered air plus a range of O3
      concentrations in combination with ambient or approximately twice-ambient CO2
      concentrations in open-top field chambers. Experimental manipulation of O3
      concentrations and estimates of plant O3 uptake indicated that equivalent O3
      fluxes that suppressed net photosynthesis, growth, and yield at ambient
      concentrations of CO2 were generally much less detrimental to plants treated
      concurrently with elevated CO2. These responses appeared unrelated to treatment
      effects on superoxide dismutase, glutathione reductase, and peroxidase activities
      and glutathione concentration. Total ascorbic acid concentration increased by 28
      72% in lower canopy leaves in response to elevated CO2 and O3 but not in upper
      canopy leaves. Increasing concentrations of atmospheric CO2 will likely
      ameliorate O3 damage to many crops due to reduced O3 uptake, increased carbon
      assimilation, and possibly as yet undetermined additional factors. The results of
      this study further suggest that elevated CO2 may increase the threshold O3 flux
      for biomass and yield loss in soybean.

PMID- 15983016
TI  - Time-related mapping of quantitative trait loci controlling grain-filling in rice
      (Oryza sativa L.).
AB  - Grain-filling is a crucial process that determines final grain yield in rice
      (Oryza sativa L.). To understand the genetic basis of dynamics of grain-filling,
      quantitative trait locus (QTL) analysis was conducted using time-related
      phenotypic data on grain-filling collected from a population of 155 recombinant
      inbred lines (F12), derived from a cross between Milyang 23 and Akihikari. Two
      QTLs detected on chromosomes 8 and 12 were strongly associated with increased
      filling percentage per panicle. These QTLs were not linked with those controlling
      spikelet numbers per panicle. This result confers the possibility of improving
      grain-filling together with an enlargement of sink size. The QTL for filling
      percentage per panicle on chromosome 8 exactly overlapped that for non-structural
      carbohydrate (NSC) content in the culm and leaf sheaths during grain-filling, and
      the Milyang 23 allele associated with increased grain-filling percentage per
      panicle was associated with decreased NSC content. Therefore, this QTL may be
      directly involved in NSC translocation from the culm and leaf sheaths to panicle.
      In addition, the Milyang 23 alleles of QTLs associated with greater spikelet
      number per panicle on chromosomes 1 and 6 were also related with a reduction in
      NSC content in the culm and leaf sheaths during grain-filling. These results
      indicate that NSC dynamics during grain-filling is partly dependent on sink size.
      NSC accumulation in the culm and leaf sheaths at the heading stage was mainly
      controlled by different genetic regulations from NSC dynamics during grain
      filling. Nitrogen dynamics during grain-filling may also be involved in
      carbohydrate dynamics.

PMID- 15983017
TI  - A mutational analysis of the ABA1 gene of Arabidopsis thaliana highlights the
      involvement of ABA in vegetative development.
AB  - Much of the literature on the phytohormone abscisic acid (ABA) describes it as a
      mediator in triggering plant responses to environmental stimuli, as well as a
      growth inhibitor. ABA-deficient mutants, however, display a stunted phenotype
      even under well-watered conditions and high relative humidity, which suggests
      that growth promotion may also be one of the roles of endogenous ABA. Zeaxanthin
      epoxidase, the product of the ABA1 gene of Arabidopsis thaliana, catalyses the
      epoxidation of zeaxanthin to antheraxanthin and violaxanthin, generating the
      epoxycarotenoid precursor of the ABA biosynthetic pathway. This paper gives a
      description of the molecular and phenotypic characterization of a large series of
      mutant alleles of the ABA1 gene, which cause different degrees of ABA deficiency,
      four of them previously isolated (aba1-1, aba1-3, aba1-4, and aba1-6) and the
      remaining five novel (san1-1, san1-2, san1-3, san1-4, and sre3). Molecular
      analysis of these alleles provides insights into the domains in which they
      compromise zeaxanthin epoxidase function. The size of the leaves, inflorescences,
      and flowers of these mutants is reduced, and their rosettes have lower fresh and
      dry weights than their wild types, as a result of a diminished cell size. Low
      concentrations of exogenous ABA increase the fresh weight of mutant and wild-type
      plants, as well as the dry weight of the mutants. The leaves of aba1 mutants are
      abnormally shaped and fail to develop clearly distinct spongy and palisade
      mesophyll layers. Taken together, these phenotypic traits indicate, as suggested
      by previous authors, that ABA acts as a growth promoter during vegetative
      development. The abnormal shape and internal structure of the leaves of aba1
      mutants suggests, in addition, a role for ABA in organogenesis.

PMID- 15983018
TI  - In situ expression of two storage protein genes in relation to histo
      differentiation at mid-embryogenesis in Medicago truncatula and Pisum sativum
      seeds.
AB  - The seed consists of several layers of specialized cell-types that divide and
      differentiate following a highly regulated programme in time and space. A
      cytological approach was undertaken in order to study the histo-differentiation
      at mid-embryogenesis in Medicago truncatula as a model legume, and in Pisum
      sativum using serial sections of embedded immature seed. Little published
      information is available about seed development in Medicago species. The
      observations from this study revealed a number of distinctive features of
      Medicago seed development and differentiation. Transfer cells, involved in
      nutrient transfer to the embryo, were clearly identified in the thin-walled
      parenchyma of the innermost integument. Histological Schiff-naphthol enabled
      carbohydrate accumulation to be followed in the different seed compartments, and
      revealed the storage protein bodies. Non-radioactive mRNA in situ hybridization,
      was carried out using mRNA probes from two highly expressed genes encoding the
      major vicilin and legumin A storage protein types. The timing of mRNA expression
      was related to that of the corresponding proteins already identified.

PMID- 15983019
TI  - Transcriptional regulation of three EIN3-like genes of carnation (Dianthus
      caryophyllus L. cv. Improved White Sim) during flower development and upon
      wounding, pollination, and ethylene exposure.
AB  - Using a combination of approaches, three EIN3-like (EIL) genes DC-EIL1/2
      (AY728191), DC-EIL3 (AY728192), and DC-EIL4 (AY728193) were isolated from
      carnation (Dianthus caryophyllus) petals. DC-EIL1/2 deduced amino acid sequence
      shares 98% identity with the previously cloned and characterized carnation DC
      EIL1 (AF261654), 62% identity with DC-EIL3, and 60% identity with DC-EIL4. DC
      EIL3 deduced amino acid sequence shares 100% identity with a previously cloned
      carnation gene fragment, Dc106 (CF259543), 61% identity with Dianthus
      caryophyllus DC-EIL1 (AF261654), and 59% identity with DC-EIL4. DC-EIL4 shared
      60% identity with DC-EIL1 (AF261654). Expression analyses performed on vegetative
      and flower tissues (petals, ovaries, and styles) during growth and development
      and senescence (natural and ethylene-induced) indicated that the mRNA
      accumulation of the DC-EIL family of genes in carnation is regulated
      developmentally and by ethylene. DC-EIL3 mRNA showed significant accumulation
      upon ethylene exposure, during flower development, and upon pollination in petals
      and styles. Interestingly, decreasing levels of DC-EIL3 mRNA were found in
      wounded leaves and ovaries of senescing flowers whenever ethylene levels
      increased. Flowers treated with sucrose showed a 2 d delay in the accumulation of
      DC-EIL3 transcripts when compared with control flowers. These observations
      suggest an important role for DC-EIL3 during growth and development. Changes in
      DC-EIL1/2 and DC-EIL4 mRNA levels during flower development, and upon ethylene
      exposure and pollination were very similar. mRNA levels of the DC-EILs in styles
      of pollinated flowers showed a positive correlation with ethylene production
      after pollination. The cloning and characterization of the EIN3-like genes in the
      present study showed their transcriptional regulation not previously observed for
      EILs.

PMID- 15983020
TI  - Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with
      ovarian failure after chemotherapy.

PMID- 15983021
TI  - Racial differences in the incidence of BRCA1 and BRCA2 mutations in a cohort of
      early onset breast cancer patients: African American compared to white women.
AB  - PURPOSE: To evaluate the frequency and distribution of BRCA1 and BRCA2 mutations
      in a cohort of young women with breast cancer and to compare the distribution of
      mutations as a function of race. METHODS: After IRB approved informed consent,
      170 white women and 30 African American women with known breast cancer diagnosed
      at a young age (45 years or less) underwent complete sequencing of the BRCA1 and
      BRCA2 genes. Each cohort represented approximately 40% of women of the same
      ethnic background aged 45 years or younger in a breast cancer database. RESULTS:
      Of the 200 patients tested, 131 (65%) had wild type mutations, 34 (17%) had
      deleterious mutations, and 35 (18%) had variants of uncertain significance. There
      were no significant differences between the white and African American cohorts
      regarding the percentage of deleterious mutations (17% v 17%). However, most
      African American patients had mutations in BRCA2 (4/5, 80%), while most mutations
      in the white cohort were in BRCA1 (20/29, 69%). In addition, 46% of the African
      American women had variants of uncertain significance, compared to only 12% of
      the white cohort. CONCLUSIONS: Young African American women with breast cancer
      have a similar frequency of deleterious mutations as white women, but have a
      significantly higher frequency of variants of uncertain significance. Review of
      these variants revealed that the majority were unlikely to be associated with
      disease risk or were likely to be polymorphisms. The implications for genetic
      testing and counselling in young women with breast cancer are discussed.

PMID- 15983022
TI  - Hyperhomocysteinaemia and aortic calcification are associated with fractures in
      patients on haemodialysis.
AB  - BACKGROUND: Fractures and atherosclerosis are common in patients with renal
      failure; this may be due to hyperhomocysteinemia. AIM: To examine the
      relationships between fractures, vascular calcification and homocysteine levels
      in haemodialysis patients. DESIGN: Cross-sectional survey. METHODS: We enrolled
      37 men and 15 women who had been on haemodialysis for at least 1 year. We
      identified prevalent spine fractures by radiographs. Non-spine fractures were
      identified by self-report and confirmed by review of radiographs or radiology
      reports. We classified the presence and severity of lumbar aortic calcifications
      with lateral lumbar radiographs. We measured serum homocysteine in all subjects
      within 30 days of study entry. RESULTS: After adjusting for age and weight,
      increased levels of homocysteine were associated with an increased risk fracture
      (OR per mmol/l increase in homocysteine 1.6, 95%CI 1.2-2.0), as was the presence
      of aortic calcification (OR 1.6, 95%CI 1.2-2.1). Homocysteine and lumbar aortic
      calcification were highly correlated (r = 0.86). DISCUSSION:
      Hyperhomocysteinaemia may explain the relationship between fractures and
      atherosclerosis in patients with renal failure.

PMID- 15983023
TI  - Control of hypertension in patients at high risk of cardiovascular disease.
AB  - BACKGROUND: Hypertension is a major cardiovascular risk factor, but knowledge
      about the real magnitude of the problem and its determinants is lacking. AIM: To
      assess control of hypertension and evaluate medical resource use, in patients at
      high risk of cardiovascular disease. DESIGN: Multicentric cross-sectional study.
      METHODS: We collected data for 2205 adult patients from 36 centres,
      representative of all regions of Spain. Patients had attended out-patient clinics
      from July 2002 to August 2003, had an absolute cardiovascular risk > or =20% at
      10 years (according to the Framingham guidelines), and had a diagnosis of
      hypertension. Pregnant and terminally ill patients were excluded. RESULTS:
      Hypertension was inadequately controlled in 1384 patients (62.8%). LDL
      cholesterol was higher in patients with uncontrolled hypertension (median 130.2
      vs. 120.0 mg/dl, p < 0.001). Haemoglobin A(1c) in diabetic patients was also
      greater in those with uncontrolled hypertension (median 7.10% vs. 6.90%, p =
      0.010). Uncontrolled hypertension was associated with the following variables, in
      descending strength of association: higher LDL cholesterol, taking
      antihypertensive medication, living in non-metropolitan areas, and higher body
      mass index. DISCUSSION: Hypertension is poorly controlled in most patients with a
      high risk of cardiovascular disease. Uncontrolled hypertension is frequently
      associated with poor control of other risk factors.

PMID- 15983024
TI  - Self-poisoning suicides in England: a multicentre study.
AB  - BACKGROUND: Suicide by self-poisoning is an important cause of death worldwide. A
      substantial proportion of those with a fatal outcome may come into contact with
      medical services before they die. AIM: To estimate the proportion of self
      poisoning suicides who reached hospital alive; to compare those who reached
      hospital alive with those who did not; to describe in detail the clinical
      characteristics and medical management of those dying in hospital. DESIGN:
      Retrospective audit. METHODS: We studied 24 coroners' jurisdictions across
      England, reviewing coroners' files and identifying all suicides by self-poisoning
      (drugs and other ingestible poisons) from 1 January 2001 to 31 December 2001.
      RESULTS: Of the 214 individuals who completed suicide by self-poisoning during
      the study period, 49 (23%) reached hospital alive. Those reaching hospital were
      more likely to be female, more likely to have ingested paracetamol and less
      likely to have ingested co-proxamol. In the hospital sample, the commonest causes
      of death were respiratory (n = 10), hepatic or hepatorenal (n = 8), cardiac (n =
      5), or a result of hypoxic brain injury (n = 5). Only 18% of in-hospital deaths
      occurred within 24 h of the overdose. DISCUSSION: Extrapolating to England as a
      whole, we might expect 300 self-poisoning suicides per year to reach hospital
      alive (6% of all suicides). Improved medical management might produce a small but
      significant reduction in the rate of suicide. Such interventions should not be
      restricted to the emergency care domain. Further research will help to clarify
      the likely contribution of improved medical management to suicide prevention.

PMID- 15983025
TI  - Clearance of moxifloxacin during continuous haemofiltration (CVVHF) in vitro.
AB  - BACKGROUND/AIMS: The clearance of moxifloxacin is reported to be unaltered in the
      presence of renal insufficiency. There is little information about the clearance
      of intravenous moxifloxacin in renal replacement therapies during intensive care.
      The aim of this study was to determine the clearance of moxifloxacin during
      continuous veno-venous haemofiltration (CVVHF) in vitro. METHODS: The elimination
      of moxifloxacin (reservoir with 600 mL of washed human erythrocytes, 100 mL of
      NaHCO3 and various amounts of Ringer solution and human albumin to give a total
      volume of 1000 mL, pH 7.35 +/- 0.5; haematocrit 41 +/- 2) during CVVHF in vitro
      with two filter conditions (during priming, after priming), three protein
      concentrations (human albumin: 0 g/L, 20 g/L, 40 g/L) and two filtration
      velocities [(i) standard condition: blood flow at 100 mL/min and turnover of 2
      L/h; (ii) blood flow at 50 mL/min and turnover of 1 L/h] were investigated.
      RESULTS: A new filter needs 20 min of priming before moxifloxacin reaches a
      steady relative filtration rate. The sieving coefficient with 0 g/L albumin was
      1.07, with 20 g/L 0.90 and with 40 g/L 0.80. Under standard filtration conditions
      (i) the renal clearance was between 26.7 and 35.7 mL/min, and under the altered
      conditions (ii) it was 15.2 mL/min. CONCLUSION: During CVVHF in vitro we found
      filtration clearances of moxifloxacin of the same order as its renal clearance in
      healthy subjects. The high sieving coefficient, nearly independent of blood
      protein concentration, would suggest that moxifloxacin is filtered almost as
      freely as creatinine. These results do not indicate a need for dose adjustment
      under appropriate haemofiltration conditions and normal hepatic function.

PMID- 15983026
TI  - In vitro activity of citropin 1.1 alone and in combination with clinically used
      antimicrobial agents against Rhodococcus equi.
AB  - OBJECTIVES: The aim of this study was to investigate the in vitro activity of
      citropin 1.1, an antimicrobial peptide derived from the Australian tree frog
      Litoria citropa, alone and in combination with ampicillin, ceftriaxone,
      doxycycline, netilmicin, ciprofloxacin, rifampicin, linezolid, vancomycin,
      clarithromycin and imipenem against 12 nosocomial isolates of Rhodococcus equi.
      METHODS: Antimicrobial activity of citropin 1.1 was measured by MIC, MBC, time
      kill studies and chequerboard titration method. RESULTS: All isolates were
      inhibited at concentrations of citropin 1.1 between 2 and 8 mg/L. Combination
      studies demonstrated synergy only when the peptide was combined with
      clarithromycin, doxycycline and rifampicin. CONCLUSIONS: Our findings show that
      citropin 1.1 is active against R. equi and that its activity could be enhanced
      when it is combined with hydrophobic antibiotics.

PMID- 15983027
TI  - Impact of rosiglitazone treatment on the bioavailability of antiretroviral
      compounds in HIV-positive patients.
AB  - OBJECTIVES: The insulin-sensitizer rosiglitazone is under investigation for
      therapy of HIV-associated lipodystrophy syndrome (LDS). Little is known about
      pharmacological interactions with antiretroviral (ARV) drugs. METHODS:
      Therapeutic drug monitoring (TDM) of ARV drugs was performed in a prospective
      study before and at day 28 after start of treatment with 4 mg of rosiglitazone
      for combined LDS. Drug levels were measured in the morning fasting, and 0.5, 1,
      2, 4, 6 and 8 h after standardized drug intake. Values were log-transformed for
      analysis. RESULTS: Twelve males and six females were assessed; mean age was 50.7
      years and mean CD4 cell count was 496 cells/mm(3). All patients had a viral load
      below 50 copies/mL, and backbone ARV therapy consisted of two or three nucleoside
      reverse transcriptase inhibitors in all cases. After administration of
      rosiglitazone, no significant differences in Cmax, Cmin and AUC were found in
      cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean Cmax of
      nevirapine (n = 4) was reduced significantly [-0.44; 95% confidence interval (CI)
      -0.86 to -0.01]. Furthermore, there was a consistent trend to a reduction in the
      geometric mean ratio (GMR) of Cmax, Cmin and AUC (GMR of Cmax 0.95; 95% CI 0.9
      1.0; GMR of Cmin 0.89; 95% CI 0.65-1.13; GMR of AUC 0.96; 95% CI 0.91-1.01).
      CONCLUSIONS: Treatment with 4 mg of rosiglitazone for HIV-associated LDS is
      likely to reduce the bioavailability of nevirapine. Thus, routine TDM is
      recommended for patients treated with rosiglitazone and nevirapine. A therapy
      consisting of efavirenz or lopinavir seems to be without negative impact. Further
      studies on the interaction of rosiglitazone with ARV drugs are necessary.

PMID- 15983028
TI  - Molecular basis of florfenicol-induced increase in adherence of Staphylococcus
      aureus strain Newman.
AB  - OBJECTIVES: The aim of this study was to determine the molecular basis of the
      florfenicol-dependent increased adherence of Staphylococcus aureus strain Newman
      to HEp-2 cells. METHODS AND RESULTS: Northern slot blot analysis showed that mRNA
      expression of fnbA, fnbB, coa, emp and eap, coding for adhesins, was increased in
      the presence of 0.5 x MIC of florfenicol. Under the same conditions expression of
      cap5, coding for type 5 capsular polysaccharides, was distinctly decreased. Since
      global regulatory systems can modulate the expression of adhesins, their role in
      this process was investigated by including three isogenic mutants with
      functionally inactive global regulator systems, agr, sar or sae. Growth in the
      presence of 0.5 x MIC of florfenicol significantly increased the adherence to HEp
      2 cells, fibronectin and fibrinogen of the Deltaagr and Deltasar mutant strains,
      but not that of the Deltasae mutant strain. In contrast to components of the agr
      or sar system, expression of saeRS was increased, suggesting a potential sae
      directed decrease in the expression of cap5 and increase in the expression of
      genes coding for adhesins under the influence of florfenicol. Analysis of RNA
      stability revealed that the increased amount of transcripts of saeRS and
      adherence-associated genes was due to a stabilization of the respective mRNAs by
      florfenicol. CONCLUSIONS: Our data provide evidence that an activation of the
      global regulator sae and a stabilization of mRNA coding for specific adhesins
      seem to act synergically in generating a more adherent phenotype in the presence
      of a high subinhibitory concentration of florfenicol.

PMID- 15983029
TI  - Susceptibility of Streptococcus mutans biofilms to photodynamic therapy: an in
      vitro study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the antimicrobial effect of
      toluidine blue O (TBO), in combination with either a helium/neon (HeNe) laser or
      a light-emitting diode (LED), on the viability and architecture of Streptococcus
      mutans biofilms. METHODS: Biofilms were grown on hydroxyapatite discs in a
      constant depth film fermentor fed with artificial saliva that was supplemented
      with 2% sucrose four times a day, thus producing a typical 'Stephan pH curve'.
      Photodynamic therapy was subsequently carried out on biofilms of various ages
      with light from either the HeNe laser or LED using energy densities of between 49
      and 294 J/cm(2). RESULTS: Significant decreases in the viability of S. mutans
      biofilms were only observed when biofilms were exposed to both TBO and light,
      when reductions in viability of up to 99.99% were observed with both light
      sources. Overall, the results showed that the bactericidal effect was light dose
      dependent and that older biofilms were less susceptible to photodynamic therapy.
      Confocal laser scanning microscopy images suggested that lethal
      photosensitization occurred predominantly in the outermost layers of the
      biofilms. CONCLUSIONS: Photodynamic therapy may be a useful approach in the
      treatment of dental plaque-related diseases.

PMID- 15983030
TI  - Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain
      shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV)
      receptor, angiotensin-converting enzyme-2 (ACE2).
AB  - Angiotensin-converting enzyme-2 (ACE2) is a critical regulator of heart function
      and a cellular receptor for the causative agent of severe-acute respiratory
      syndrome (SARS), SARS-CoV (coronavirus). ACE2 is a type I transmembrane protein,
      with an extracellular N-terminal domain containing the active site and a short
      intracellular C-terminal tail. A soluble form of ACE2, lacking its cytosolic and
      transmembrane domains, has been shown to block binding of the SARS-CoV spike
      protein to its receptor. In this study, we examined the ability of ACE2 to
      undergo proteolytic shedding and investigated the mechanisms responsible for this
      shedding event. We demonstrated that ACE2, heterologously expressed in HEK293
      cells and endogenously expressed in Huh7 cells, undergoes metalloproteinase
      mediated, phorbol ester-inducible ectodomain shedding. By using inhibitors with
      differing potency toward different members of the ADAM (a disintegrin and
      metalloproteinase) family of proteases, we identified ADAM17 as a candidate
      mediator of stimulated ACE2 shedding. Furthermore, ablation of ADAM17 expression
      using specific small interfering RNA duplexes reduced regulated ACE2 shedding,
      whereas overexpression of ADAM17 significantly increased shedding. Taken
      together, these data provided direct evidence for the involvement of ADAM17 in
      the regulated ectodomain shedding of ACE2. The identification of ADAM17 as the
      protease responsible for ACE2 shedding may provide new insight into the
      physiological roles of ACE2.

PMID- 15983031
TI  - p53-dependent caspase-2 activation in mitochondrial release of apoptosis-inducing
      factor and its role in renal tubular epithelial cell injury.
AB  - We demonstrate the role of p53-mediated caspase-2 activation in the mitochondrial
      release of apoptosis-inducing factor (AIF) in cisplatin-treated renal tubular
      epithelial cells. Gene silencing of AIF with its small interfering RNA (siRNA)
      suppressed cisplatin-induced AIF expression and provided a marked protection
      against cell death. Subcellular fractionation and immunofluorescence studies
      revealed cisplatin-induced translocation of AIF from the mitochondria to the
      nuclei. Pancaspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone or
      p53 inhibitor pifithrin-alpha markedly prevented mitochondrial release of AIF,
      suggesting that caspases and p53 are involved in this release. Caspase-2 and -3
      that were predominantly activated in response to cisplatin provided a unique
      model to study the role of these caspases in AIF release. Cisplatin-treated
      caspase-3 (+/+) and caspase-3 (-/-) cells exhibited similar AIF translocation to
      the nuclei, suggesting that caspase-3 does not affect AIF translocation, and
      thus, caspase-2 may be involved in the translocation. Caspase-2 inhibitor
      benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethylketone or down-regulation of
      caspase-2 by its siRNA significantly prevented translocation of AIF. Caspase-2
      activation was a critical response from p53, which was markedly induced and
      phosphorylated in cisplatin-treated cells. Overexpression of p53 not only
      resulted in caspase-2 activation but also mitochondrial release of AIF. The p53
      inhibitor pifithrin-alpha or p53 siRNA prevented both cisplatin-induced caspase-2
      activation and mitochondrial release of AIF. Caspase-2 activation was dependent
      on the p53-responsive gene, PIDD, a death domain-containing protein that was
      induced by cisplatin in a p53-dependent manner. These results suggest that
      caspase-2 activation mediated by p53 is an important pathway involved in the
      mitochondrial release of AIF in response to cisplatin injury.

PMID- 15983032
TI  - BRCA1 interaction with human papillomavirus oncoproteins.
AB  - Previously, we reported that BRCA1 strongly represses the transcriptional
      activity of estrogen receptor-alpha (ER-alpha) in human breast and prostate
      cancer cells but only weakly inhibits ER-alpha in cervical cancer cells. We now
      report that introduction of the human papillomavirus E7 or E6 oncogenes into
      human papillomavirus-negative cells rescues the BRCA1 repression of ER-alpha
      activity and that the E7 and E6 oncoproteins interact directly with BRCA1 in
      vitro and associate with BRCA1 in vivo in cultured cells. This interaction
      involves at least two contact points on BRCA1, one within an N-terminal site
      shown previously to interact with ER-alpha and the other in a C-terminal region
      of BRCA1 containing the first BRCA1 C-terminal domain. Point mutations within the
      zinc finger domains of E7 and E6 inactivated the binding to the N terminus of
      BRCA1 and reduced their ability to rescue BRCA1 inhibition of ER-alpha. E6 and E7
      also antagonized the ability of BRCA1 to inhibit c-Myc E-box-mediated
      transactivation and human telomerase reverse transcriptase promoter activity, in
      a manner dependent upon the zinc finger domains. Finally, the ability of E6 and
      E7 to antagonize BRCA1 did not involve proteolytic degradation of BRCA1. These
      findings suggest functional interactions of BRCA1 with E7 and E6. The potential
      significance of these findings is discussed.

PMID- 15983033
TI  - Mitochondrial respiration and ATP production are significantly impaired in
      striatal cells expressing mutant huntingtin.
AB  - There is significant evidence that energy production impairment and mitochondrial
      dysfunction play a role in the pathogenesis of Huntington disease. Nonetheless,
      the specific mitochondrial defects due to the presence of mutant huntingtin have
      not been fully elucidated. To determine the effects of mutant huntingtin on
      mitochondrial energy production, a thorough analysis of respiration, ATP
      production, and functioning of the respiratory complexes was carried out in
      clonal striatal cells established from Hdh(Q7) (wild-type) and Hdh(Q111) (mutant
      huntingtin knock-in) mouse embryos. Mitochondrial respiration and ATP production
      were significantly reduced in the mutant striatal cells compared with the wild
      type cells when either glutamate/malate or succinate was used as the substrate.
      However, mitochondrial respiration was similar in the two cell lines when the
      artificial electron donor TMPD/ascorbate, which feeds into complex IV, was used
      as the substrate. The attenuation of mitochondrial respiration and ATP production
      when either glutamate/malate or succinate was used as the substrate was not due
      to impairment of the respiratory complexes, because their activities were
      equivalent in both cell lines. Intriguingly, in the striatum of presymptomatic
      and pathological grade 1 Huntington disease cases there is also no impairment of
      mitochondrial complexes I-IV (Guidetti, P., Charles, V., Chen, E. Y., Reddy, P.
      H., Kordower, J. H., Whetsell, W. O., Jr., Schwarcz, R., and Tagle, D. A. (2001)
      Exp. Neurol. 169, 340-350). To our knowledge, this is the first comprehensive
      analysis of the effects of physiological levels of mutant huntingtin on
      mitochondrial respiratory function within an appropriate cellular context. These
      findings demonstrate that the presence of mutant huntingtin impairs mitochondrial
      ATP production through one or more mechanisms that do not directly affect the
      function of the respiration complexes.

PMID- 15983034
TI  - Persistent nicotine treatment potentiates amplification of the dihydrofolate
      reductase gene in rat lung epithelial cells as a consequence of Ras activation.
AB  - Although nicotine has been suggested to promote lung carcinogenesis, the
      mechanism of its action in this process remains unknown. The present
      investigation demonstrates that the treatment of rat lung epithelial cells with
      nicotine for various periods differentially mobilizes multiple intracellular
      pathways. Protein kinase C and phosphoinositide 3-OH-kinase are transiently
      activated after the treatment. Also, Ras and its downstream effector ERK1/2 are
      activated after long term exposure to nicotine. The activation of Ras by nicotine
      treatment is responsible for the subsequent perturbation of the methotrexate
      (MTX)-mediated G1 cell cycle restriction as well as an increase in production of
      reactive oxygen species. When p53 expression is suppressed by introducing E6,
      persistent exposure to nicotine enables dihydrofolate reductase gene
      amplification in the presence of methotrexate (MTX) and the formation of the MTX
      resistant colonies. Altering the activity of phosphoinositide 3-OH-kinase has no
      effect on dihydrofolate reductase amplification. However, the suppression of
      protein kinase C dramatically affects the colony formation in soft agar. Thus,
      our data suggest that persistent exposure to nicotine perturbs the G1 checkpoint
      and causes DNA damage through the increase of the production of reactive oxygen
      species. However, a third element rendered by loss of p53 is required for the
      initiation of the process of gene amplification. Under p53-deficient conditions,
      the establishment of a full oncogenic transformation, in response to long term
      nicotine exposure, is achieved through the cooperation of multiple signaling
      pathways.

PMID- 15983035
TI  - A novel alpha-conotoxin, PeIA, cloned from Conus pergrandis, discriminates
      between rat alpha9alpha10 and alpha7 nicotinic cholinergic receptors.
AB  - The alpha9 and alpha10 nicotinic cholinergic subunits assemble to form the
      receptor believed to mediate synaptic transmission between efferent olivocochlear
      fibers and hair cells of the cochlea, one of the few examples of postsynaptic
      function for a non-muscle nicotinic acetylcholine receptor (nAChR). However, it
      has been suggested that the expression profile of alpha9 and alpha10 overlaps
      with that of alpha7 in the cochlea and in sites such as dorsal root ganglion
      neurons, peripheral blood lymphocytes, developing thymocytes, and skin. We now
      report the cloning, total synthesis, and characterization of a novel toxin alpha
      conotoxin PeIA that discriminates between alpha9alpha10 and alpha7 nAChRs. This
      is the first toxin to be identified from Conus pergrandis, a species found in
      deep waters of the Western Pacific. Alpha-conotoxin PeIA displayed a 260-fold
      higher selectivity for alpha-bungarotoxin-sensitive alpha9alpha10 nAChRs compared
      with alpha-bungarotoxin-sensitive alpha7 receptors. The IC50 of the toxin was 6.9
      +/- 0.5 nM and 4.4 +/- 0.5 nM for recombinant alpha9alpha10 and wild-type hair
      cell nAChRs, respectively. Alpha-conotoxin PeIA bears high resemblance to alpha
      conotoxins MII and GIC isolated from Conus magus and Conus geographus,
      respectively. However, neither alpha-conotoxin MII nor alpha-conotoxin GIC at
      concentrations of 10 microM blocked acetylcholine responses elicited in Xenopus
      oocytes injected with the alpha9 and alpha10 subunits. Among neuronal non-alpha
      bungarotoxin-sensitive receptors, alpha-conotoxin PeIA was also active at
      alpha3beta2 receptors and chimeric alpha6/alpha3beta2beta3 receptors. Alpha
      conotoxin PeIA represents a novel probe to differentiate responses mediated
      either through alpha9alpha10 or alpha7 nAChRs in those tissues where both
      receptors are expressed.

PMID- 15983036
TI  - Mouse and human resistins impair glucose transport in primary mouse
      cardiomyocytes, and oligomerization is required for this biological action.
AB  - The adipocytokine resistin impairs glucose tolerance and insulin sensitivity in
      rodents. Here, we examined the effect of resistin on glucose uptake in isolated
      adult mouse cardiomyocytes. Murine resistin reduced insulin-stimulated glucose
      uptake, establishing the heart as a resistin target tissue. Notably, human
      resistin also impaired insulin action in mouse cardiomyocytes, providing the
      first evidence that human and mouse resistin homologs have similar functions.
      Resistin is a cysteine-rich molecule that circulates as a multimer of a dimeric
      form dependent upon a single intermolecular disulfide bond, which, in the mouse,
      involves Cys26; mutation of this residue to alanine (C26A) produces a monomeric
      molecule that appears to be bioactive in the liver. Remarkably, unlike native
      resistin, monomeric C26A resistin had no effect on basal or insulin-stimulated
      glucose uptake in mouse cardiomyocytes. Resistin impairs glucose uptake in
      cardiomyocytes by mechanisms that involve altered vesicle trafficking. Thus, in
      cardiomyocytes, both mouse and human resistins directly impair glucose transport;
      and in contrast to effects on the liver, these actions of resistin require
      oligomerization.

PMID- 15983037
TI  - Motion of carboxyl terminus of Galpha is restricted upon G protein activation. A
      solution NMR study using semisynthetic Galpha subunits.
AB  - The carboxyl terminus of the G protein alpha subunit plays a key role in
      interactions with G protein-coupled receptors. Previous studies that have
      incorporated covalently attached probes have demonstrated that the carboxyl
      terminus undergoes conformational changes upon G protein activation. To examine
      the conformational changes that occur at the carboxyl terminus of Galpha subunits
      upon G protein activation in a more native system, we generated a semisynthetic
      Galpha subunit, site-specifically labeled in its carboxyl terminus with 13C amino
      acids. Using expressed protein ligation, 9-mer peptides were ligated to
      recombinant Galpha(i1) subunits lacking the corresponding carboxyl-terminal
      residues. In a receptor-G protein reconstitution assay, the truncated Galpha(i1)
      subunit could not be activated by receptor; whereas the semisynthetic protein
      demonstrated functionality that was comparable with recombinant Galpha(i1). To
      study the conformation of the carboxyl terminus of the semisynthetic G protein,
      we applied high resolution solution NMR to Galpha subunits containing 13C labels
      at the corresponding sites in Galpha(i1): Leu-348 (uniform), Gly-352 (alpha
      carbon), and Phe-354 (ring). In the GDP-bound state, the spectra of the ligated
      carboxyl terminus appeared similar to the spectra obtained for 13C-labeled free
      peptide. Upon titration with increasing concentrations of AlF4-, the 13C
      resonances demonstrated a marked loss of signal intensity in the semisynthetic
      Galpha subunit but not in free peptide subjected to the same conditions. Because
      AlF4- complexes with GDP to stabilize an activated state of the Galpha subunit,
      these results suggest that the Galpha carboxyl terminus is highly mobile in its
      GDP-bound state but adopts an ordered conformation upon activation by AlF4-.

PMID- 15983038
TI  - S-adenosylmethionine blocks collagen I production by preventing transforming
      growth factor-beta induction of the COL1A2 promoter.
AB  - To study the anti-fibrogenic mechanisms of S-adenosylmethionine (AdoMet),
      transgenic mice harboring the -17 kb to +54 bp of the collagen alpha2 (I)
      promoter (COL1A2) cloned upstream from the beta-gal reporter gene were injected
      with carbon tetrachloride (CCl4) to induce fibrosis and coadministered either
      AdoMet or saline. Control groups received AdoMet or mineral oil. AdoMet lowered
      the pathology in CCl4-treated mice as shown by transaminase levels, hematoxylin
      and eosin, Masson's trichrome staining, and collagen I expression. beta
      Galactosidase activity indicated activation of the COL1A2 promoter in stellate
      cells from CCl4-treated mice and repression of such activation by AdoMet. Lipid
      peroxidation, transforming growth factor-beta (TGFbeta) expression, and decreases
      in glutathione levels were prevented by AdoMet. Incubation of primary stellate
      cells with AdoMet down-regulated basal and TGFbeta-induced collagen I and alpha
      smooth muscle actin proteins. AdoMet metabolites down-regulated collagen I
      protein and mRNA levels. AdoMet repressed basal and TGFbeta-induced reporter
      activity in stellate cells transfected with COL1A2 promoter deletion constructs.
      AdoMet blocked TGFbeta induction of the -378 bp region of the COL1A2 promoter and
      prevented the phosphorylation of extracellular signal-regulated kinase 1/2 and
      the binding of Sp1 to the TGFbeta-responsive element. These observations unveil a
      novel mechanism by which AdoMet could ameliorate liver fibrosis.

PMID- 15983039
TI  - Glycosylation influences the lectin activities of the macrophage mannose
      receptor.
AB  - The mannose receptor (MR) is a heavily glycosylated endocytic receptor that
      recognizes both mannosylated and sulfated ligands through its C-type lectin
      domains and cysteine-rich (CR) domain, respectively. Differential binding
      properties have been described for MR isolated from different sources, and we
      hypothesized that this could be due to altered glycosylation. Using MR
      transductants and purified MR, we demonstrate that glycosylation differentially
      affects both MR lectin activities. MR transductants generated in glycosylation
      mutant cell lines lacked most mannose internalization activity, but could
      internalize sulfated glycans. Accordingly, purified MR bearing truncated Man5
      GlcNAc2 glycans (Man5 -MR) or non-sialylated complex glycans (SA0-MR) did not
      bind mannosylated glycans, but could recognize SO4-3-Gal in vitro. Additional
      studies showed that, although mannose recognition was largely independent of the
      oligomerization state of the protein, recognition of sulfated carbohydrates was
      mostly mediated by self-associated MR and that, in SA0-MR, there was a higher
      proportion of oligomeric MR. These results suggest that self-association could
      lead to multiple presentation of CR domains and enhanced avidity for sulfated
      sugars and that non-sialylated MR is predisposed to oligomerize. Therefore, the
      glycosylation of MR, terminal sialylation in particular, could influence its
      binding properties at two levels. (i) It is required for mannose recognition; and
      (ii) it modulates the tendency of MR to self-associate, effectively regulating
      the avidity of the CR domain for sulfated sugar ligands.

PMID- 15983040
TI  - NADPH oxidase restrains the matrix metalloproteinase activity of macrophages.
AB  - Matrix metalloproteinases (MMPs) regulate numerous functions in normal and
      disease processes; thus, irreversibly blocking their activity is a key step in
      regulating MMP catalysis. We previously showed in vitro that oxidizing
      intermediates generated by phagocytes inactivate MMPs by modifying specific amino
      acids. To assess whether this mechanism operates in vivo, we focused on MMP-12, a
      macrophage-specific MMP known to mediate emphysema in mouse models. We found that
      mice lacking gp91(phox), a phagocyte-specific component of the NADPH oxidase,
      developed extensive, spontaneous emphysematous destruction of their peripheral
      air spaces, whereas mice deficient in both NADPH oxidase and MMP-12 were
      protected from spontaneous emphysema. Although gp91(phox)-null and wild-type
      macrophages produced equivalent levels of MMP-12 protein, the oxidant-deficient
      cells had greater MMP-12 activity than wild-type macrophages. These findings
      indicate that reactive intermediates provide a physiological mechanism to protect
      tissues from excessive macrophage-mediated damage during inflammation.

PMID- 15983041
TI  - Effects of mutagenesis in the switch I region and conserved arginines of
      Escherichia coli MnmE protein, a GTPase involved in tRNA modification.
AB  - MnmE is an evolutionarily conserved, three domain GTPase involved in tRNA
      modification. In contrast to Ras proteins, MnmE exhibits a high intrinsic GTPase
      activity and requires GTP hydrolysis to be functionally active. Its G domain
      conserves the GTPase activity of the full protein, and thus, it should contain
      the catalytic residues responsible for this activity. In this work, mutational
      analysis of all conserved arginine residues of the MnmE G-domain indicates that
      MnmE, unlike other GTPases, does not use an arginine finger to drive catalysis.
      In addition, we show that residues in the G2 motif (249GTTRD253), which resides
      in the switch I region, are not important for GTP binding but play some role in
      stabilizing the transition state, specially Gly249 and Thr251. On the other hand,
      G2 mutations leading to a minor loss of the GTPase activity result in a non
      functional MnmE protein. This indicates that GTP hydrolysis is a required but non
      sufficient condition so that MnmE can mediate modification of tRNA. The
      conformational change of the switch I region associated with GTP hydrolysis seems
      to be crucial for the function of MnmE, and the invariant threonine (Thr251) of
      the G2 motif would be essential for such a change, because it cannot be
      substituted by serine. MnmE defects result in impaired growth, a condition that
      is exacerbated when defects in other genes involved in the decoding process are
      simultaneously present. This behavior is reminiscent to that found in yeast and
      stresses the importance of tRNA modification for gene expression.

PMID- 15983042
TI  - The association of the antenna system to photosystem I in higher plants.
      Cooperative interactions stabilize the supramolecular complex and enhance red
      shifted spectral forms.
AB  - We report on the association of the antenna system to the reaction center in
      Photosystem I. Biochemical analysis of mutants depleted in antenna polypeptides
      showed that the binding of the antenna moiety is strongly cooperative. The
      minimal building block for the antenna system was shown to be a dimer. Specific
      protein-protein interactions play an important role in antenna association, and
      the gap pigments, bound at the interface between core and antenna, are proposed
      to mediate these interactions Gap pigments have been characterized by comparing
      the spectra of the Photosystem I to those of the isolated antenna and core
      components. CD spectroscopy showed that they are involved in pigment-pigment
      interactions, supporting their relevance in energy transfer from antenna to the
      reaction center. Moreover, gap pigments contribute to the red-shifted emission
      forms of Photosystem I antenna. When compared with Photosystem II, the
      association of peripheral antenna complexes in PSI appears to be more stable, but
      far less flexible and functional implications are discussed.

PMID- 15983043
TI  - Disruption of the coenzyme binding site and dimer interface revealed in the
      crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant.
AB  - Mitochondrial aldehyde dehydrogenase (ALDH2) is the major enzyme that oxidizes
      ethanol-derived acetaldehyde. A nearly inactive form of the enzyme, ALDH2*2, is
      found in about 40% of the East Asian population. This variant enzyme is defined
      by a glutamate to lysine substitution at residue 487 located within the
      oligomerization domain. ALDH2*2 has an increased Km for its coenzyme, NAD+, and a
      decreased kcat, which lead to low activity in vivo. Here we report the 2.1 A
      crystal structure of ALDH2*2. The structure shows a large disordered region
      located at the dimer interface that includes much of the coenzyme binding cleft
      and a loop of residues that form the base of the active site. As a consequence of
      these structural changes, the variant enzyme exhibits rigid body rotations of its
      catalytic and coenzyme-binding domains relative to the oligomerization domain.
      These structural perturbations are the direct result of the inability of lysine
      487 to form important stabilizing hydrogen bonds with arginines 264 and 475.
      Thus, the elevated Km for coenzyme exhibited by this variant probably reflects
      the energetic penalty for reestablishing this site for productive coenzyme
      binding, whereas the structural alterations near the active site are consistent
      with the lowered Vmax.

PMID- 15983044
TI  - Scission of the lactyl ether bond of N-acetylmuramic acid by Escherichia coli
      "etherase".
AB  - The ubiquitous bacterial cell wall sugar N-acetylmuramic acid (MurNAc) carries a
      unique D-lactyl ether substituent at the C3 position. Recently, we proposed an
      etherase capable of cleaving this lactyl ether to be part of the novel bacterial
      MurNAc dissimilation pathway (Dahl, U., Jaeger, T., Nguyen, B. T., Sattler, J.
      M., Mayer, C. (2004) J. Bacteriol. 186, 2385-2392). Here, we report the
      identification of the first known MurNAc etherase. The encoding gene murQ is
      located at 55 min on the Escherichia coli chromosome adjacent to murP, the MurNAc
      specific phosphotransferase system. A murQ deletion mutant could not grow on
      MurNAc as the sole source of carbon and energy but could be complemented by
      expressing murQ from a plasmid. The mutant had no obvious phenotype when grown on
      different carbon sources but accumulated MurNAc 6-phosphate at millimolar
      concentrations from externally supplied MurNAc. Purified MurQ-His6 fusion protein
      and extracts of cells expressing murQ both catalyze the cleavage of MurNAc 6
      phosphate, with GlcNAc 6-phosphate and D-lactate being the primary products. The
      18O label from enriched water is incorporated into the sugar molecule, showing
      that the C3-O bond is cleaved and reformed by the enzyme. Moreover, an
      intermediate was detected and identified as an unsaturated sugar molecule. Based
      on this observation, we suggested a lyase-type mechanism (beta
      elimination/hydration) for the cleavage of the lactyl ether bond of MurNAc 6
      phosphate. Close homologs of murQ were found on the chromosome of several
      bacteria, and amino acid sequence similarity with the N-terminal domain of human
      glucokinase-regulatory protein (GckR or GKRP) was recognized.

PMID- 15983045
TI  - Socs1 deficiency enhances hepatic insulin signaling.
AB  - Suppressor of cytokine signaling 1 (SOCS1) is an intracellular inhibitor of
      cytokine, growth factor, and hormone signaling. Socs1-/- mice die before weaning
      from a multiorgan inflammatory disease. Neonatal Socs1-/- mice display severe
      hypoglycemia and hypoinsulinemia. Concurrent interferon gamma gene deletion (Ifng
      /-) prevented inflammation and corrected the hypoglycemia. In hyperinsulinemic
      clamp studies, however, Socs1-/- Ifng-/- mice had enhanced hepatic insulin
      sensitivity demonstrated by greater suppression of endogenous glucose production
      compared with controls with no difference in glucose disposal. Socs1-/- Ifng-/-
      mice had elevated liver insulin receptor substrate 2 expression (IRS-2) and IRS-2
      tyrosine phosphorylation. This was associated with lower phosphoenolpyruvate
      carboxykinase mRNA expression. These effects were not associated with elevated
      hepatic AMP-activated protein kinase activity. Hepatic insulin sensitivity and
      IRS-2 levels play central roles in the pathogenesis of type 2 diabetes. Socs1
      deficiency increases IRS-2 expression and enhances hepatic insulin sensitivity in
      vivo indicating that inhibition of SOCS1 may be a logical strategy in type 2
      diabetes.

PMID- 15983046
TI  - Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets
      Keap1 for degradation by a proteasome-independent pathway.
AB  - Keap1 is a BTB-Kelch protein that functions as a substrate adaptor protein for a
      Cul3-dependent E3 ubiquitin ligase complex. Keap1 targets its substrate, the Nrf2
      transcription factor, for ubiquitination and subsequent degradation by the 26 S
      proteasome. Inhibition of Keap1-dependent ubiquitination of Nrf2 increases steady
      state levels of Nrf2 and enables activation of cytoprotective Nrf2-dependent
      genes. In this report, we demonstrate that Keap1 and three other BTB-Kelch
      proteins, including GAN1, ENC1, and Sarcosin, are ubiquitinated by a Cul3
      dependent complex. Ubiquitination of Keap1 is markedly increased in cells exposed
      to quinone-induced oxidative stress, occurs in parallel with inhibition of Keap1
      dependent ubiquitination of Nrf2, and results in decreased steady-state levels of
      Keap1, particularly in cells that are unable to synthesize glutathione.
      Degradation of Keap1 is independent of the 26 S proteasome, because inhibitors of
      the 26 S proteasome do not prevent loss of Keap1 following exposure of cells to
      quinone-induced oxidative stress. Our results suggest that a switch from
      substrate to substrate adaptor ubiquitination is a critical regulatory step that
      controls steady-state levels of both BTB-Kelch substrate adaptor proteins and
      their cognate substrates.

PMID- 15983047
TI  - Isolation of TAK-779-resistant HIV-1 from an R5 HIV-1 GP120 V3 loop library.
AB  - The human immunodeficiency virus (HIV-1) envelope glycoprotein (GP) 120 interacts
      with CD4 and the CCR5 coreceptor for viral entry. The V3 loop in GP120 is a
      crucial region for determining coreceptor usage during viral entry, and a variety
      of amino acid substitutions has been observed in clinical isolates. To construct
      an HIV-1 V3 loop library, we chose 10 amino acid positions in the V3 loop and
      incorporated random combinations (27,648 possibilities) of the amino acid
      substitutions derived from 31 R5 viruses into the V3 loop of HIV-1(JR-FL)
      proviral DNA. The constructed HIV-1 library contained 6.6 x 10(6) independent
      clones containing a set of 0-10 amino acid substitutions in the V3 loop. To
      address whether restricted steric alteration in the V3 loop could confer
      resistance to an entry inhibitor, TAK-779, we selected entry inhibitor-resistant
      HIV-1 by increasing the concentration of TAK-779 from 0.10 to 0.30 microM in PM1
      CCR5 cells with high expression of CCR5. The selected viruses at passage 8
      contained five amino acid substitutions in the V3 loop without any other
      mutations in GP120 and showed 15-fold resistance compared with the parental
      virus. These results indicated that a certain structure of the V3 loop containing
      amino acid substitutions derived from 31 R5 viruses can contribute to the
      acquisition of resistance to entry inhibitors binding to CCR5. Taken together,
      this type of HIV-1 V3 loop library is useful for isolating and analyzing the
      specific biological features of HIV-1 with respect to alterations of the V3 loop
      structure.

PMID- 15983048
TI  - Proteasome-mediated degradation of STAT1alpha following infection of macrophages
      with Leishmania donovani.
AB  - Activation of the Janus-activated kinase 2 (JAK2)/STAT1alpha signaling pathway is
      repressed in Leishmania-infected macrophages. This represents an important
      mechanism by which this parasite subverts the microbicidal functions of the cell
      to promote its own survival and propagation. We recently provided evidence that
      the protein tyrosine phosphatase (PTP) SHP-1 was responsible for JAK2
      inactivation. However, STAT1 translocation to the nucleus was not restored in the
      absence of SHP-1. In the present study, we have used B10R macrophages to study
      the mechanism by which this Leishmania-induced STAT1 inactivation occurs.
      STAT1alpha nuclear localization was shown to be rapidly reduced by the infection.
      Western blot analysis revealed that cellular STAT1alpha, but not STAT3, was
      degraded. Using PTP inhibitors and an immortalized bone marrow-derived macrophage
      cell line from SHP-1-deficient mice, we showed that STAT1 inactivation was
      independent of PTP activity. However, inhibition of macrophage proteasome
      activity significantly rescued Leishmania-induced STAT1alpha degradation. We
      further demonstrated that degradation was receptor-mediated and involved protein
      kinase C alpha. All Leishmania species tested (L. major, L. donovani, L.
      mexicana, L. braziliensis), but not the related parasite Trypanosoma cruzi,
      caused STAT1alpha degradation. Collectively, results from this study revealed a
      new mechanism for STAT1 regulation by a microbial pathogen, which favors its
      establishment and propagation within the host.

PMID- 15983051
TI  - Reflections on sexual offender notification laws.

PMID- 15983049
TI  - N1-aminopropylagmatine, a new polyamine produced as a key intermediate in
      polyamine biosynthesis of an extreme thermophile, Thermus thermophilus.
AB  - In the extreme thermophile Thermus thermophilus, a disruption mutant of a gene
      homologous to speB (coding for agmatinase = agmatine ureohydrolase) accumulated
      N1-aminopropylagmatine (N8-amidino-1,8-diamino-4-azaoctane, N8
      amidinospermidine), a new compound, whereas all other polyamines produced by the
      wild-type strain were absent from the cells. Double disruption of speB and speE
      (polyamine aminopropyltransferase) resulted in the disappearance of N1
      aminopropylagmatine and the accumulation of agmatine. These results suggested the
      following. 1) N1-Aminopropylagmatine is produced from agmatine by the action of
      an enzyme coded by speE. 2) N1-Aminopropylagmatine is a metabolic intermediate in
      the biosynthesis of unique polyamines found in the thermophile. 3) N1
      Aminopropylagmatine is a substrate of the SpeB homolog. They further suggest a
      new biosynthetic pathway in T. thermophilus, by which polyamines are formed from
      agmatine via N1-aminopropylagmatine. To confirm our speculation, we purified the
      expression product of the speB homolog and confirmed that the enzyme hydrolyzes
      N1-aminopropylagmatine to spermidine but does not act on agmatine.

PMID- 15983050
TI  - The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor
      protein and inhibits amyloid-beta production.
AB  - Alzheimer disease (AD), the most common senile dementia, is characterized by
      amyloid plaques, vascular amyloid, neurofibrillary tangles, and progressive
      neurodegeneration. Amyloid is mainly composed by amyloid-beta (A(beta)) peptides,
      which are derive from processing of the beta-amyloid precursor protein (APP),
      better named amyloid-beta precursor protein (A(beta)PP), by secretases. The
      A(beta)PP intracellular domain (AID), which is released together with A(beta),
      has signaling function, since it modulates apoptosis and transcription. Despite
      its biological and pathological importance, the mechanisms regulating A(beta)PP
      processing are poorly understood. As cleavage of other gamma-secretase substrates
      is regulated by membrane bound proteins, we have postulated the existence of
      integral membrane proteins that bind A(beta)PP and regulate its processing. Here,
      we show that BRI2, a type II membrane protein, interacts with A(beta)PP.
      Interestingly, 17 amino acids corresponding to the NH2-terminal portion of
      A(beta) are necessary for this interaction. Moreover, BRI2 expression regulates
      A(beta)PP processing resulting in reduced A(beta) and AID levels. Altogether,
      these findings characterize the BRI2-A(beta)PP interaction as a regulatory
      mechanism of A(beta)PP processing that inhibits A(beta) production. Notably, BRI2
      mutations cause familial British (FBD) and Danish dementias (FDD) that are
      clinically and pathologically similar to AD. Finding that BRI2 pathogenic
      mutations alter the regulatory function of BRI2 on A(beta)PP processing would
      define dysregulation of A(beta)PP cleavage as a pathogenic mechanism common to
      AD, FDD, and FBD.

PMID- 15983052
TI  - Reintegrating seriously violent and personality-disordered offenders from a
      supermaximum security institution into the general offender population.
AB  - Offenders who have committed serious violent acts while incarcerated are often
      segregated and housed in supermaximum security facilities. Given the highly
      restricted regime under which they are detained, it is often difficult to decide
      if they are safe enough to be discharged. However, there is a need to reintegrate
      them into the general offender population in a lower security institution for
      humane, correctional, and financial reasons. We propose a transitional strategy
      to facilitate their reintegration by way of a maximum-security step-down
      treatment-oriented facility within which both their security requirements and
      treatment needs could be adequately met. The present study reports the results of
      such an approach. More than 80% of the offenders (n = 31) were reintegrated into
      a lower-security facility without relapsing and being returned to the
      supermaximum institutions within a follow-up period of 20 months. They also have
      lower institutional offense rate postreintegration compared to prereintegration.

PMID- 15983053
TI  - Korean version of the notification policy on sexual offenders: did it enhance
      public awareness of sexual crimes against minors?
AB  - This study reviewed the public notification policy of sexual offenders against
      minors in South Korea as compared to community notification programs in the
      United States. The study then examined the policy's impact on increasing the
      general public's awareness of such sexual crimes. This is based on the assumption
      that heightening public awareness can be a starting point in combating such
      crimes. Results of the data, drawn from a sample of 1,409 Koreans across the
      nation, showed that the notification policy enhanced public awareness. Factors
      related to this increase in awareness were people's concern about or familiarity
      with the policy and people's experience in identifying the existence of known
      sexual offenders in their communities. Based on the results of this study,
      strategies for enhancing public awareness of sexual crimes on minors were
      formulated. The need to develop treatment programs for sexual offenders was
      likewise highlighted.

PMID- 15983054
TI  - Predicting recidivism in a communitarian society: China.
AB  - Research on the prediction of recidivism has largely been an enterprise of
      Western criminology. Therefore, the identification and selection of predictors
      has tended to follow the individualistic traditions of the West. Important
      advances in models and methods have not been extended to non-Western societies
      such as China. This article explores the implications of communitarian features
      of Chinese urban communities for prediction of recidivism. The article applies
      the perspective of social capital to the specification of predictors. Available
      community social-capital measures are included in the prediction model to capture
      the effects of communitarian cultural features. The results indicate that social
      capital variables generally have significant effects.

PMID- 15983055
TI  - Participation in operation starting line, experience of negative emotions, and
      incidence of negative behavior.
AB  - The prison industry in the United States has experienced an unprecedented period
      of growth during the past three decades. Growing dissatisfaction with the
      monetary investment in the criminal justice system, state-level budget
      constraints, and high recidivism rates have led many criminal justice
      professionals to rethink issues of offender resocialization and rehabilitation.
      Faith-based prison programs are increasingly being used as inexpensive methods
      for potentially improving the institutional behavior of inmates and reducing
      their likelihood of postrelease arrest. Unfortunately, however, there is little
      systematic research on this issue. Using data from Mississippi's largest state
      prison, the authors explore the relationship between participation in the faith
      based prison event, Operation Starting Line, and subsequent experience of
      negative emotions and incidence of negative behaviors. Descriptive results
      suggest modest, yet positive, effects of attendance at the event. The article
      concludes with comments about the potential efficacy of faith-based prison
      programs and suggestions for future research.

PMID- 15983056
TI  - Gender, traditionalism, and attitudes toward domestic violence within a closed
      community.
AB  - This research was aimed at examining the attitudes toward domestic violence of
      people living in communal secular and religious kibbutzim. The findings,
      disregarding gender or traditionalism, indicate that most of the kibbutz members
      examined view the kibbutz as almost totally lacking any problem of violence
      toward women by their partners. The belief that the kibbutz home is a secure
      place for women within the family framework appears, surprisingly, at a higher
      frequency among women than among men. There are two possible theoretical
      explanations for this finding. First, the kibbutz lifestyle has indeed brought
      about equal power relationships, which explains why domestic violence is not
      viewed as a social problem, mostly by secular women. Second, women, who play a
      relatively minor role in constructing the public agenda in the kibbutz, have not
      become aware of the existence of this issue in the closed community.

PMID- 15983057
TI  - Evaluating the effects of birth complications on low self-control in a sample of
      twins.
AB  - Gottfredson and Hirschi's general theory has generated an abundance of research
      examining the effects of low self-control on crime and analogous behaviors. Less
      research, however, has focused on the factors that contribute to the development
      of low self-control. Gottfredson and Hirschi maintain that ineffective parents
      are the sole cause for the emergence of low self-control. At the same time, they
      disregard the possibility that low self-control has a biological or genetic
      component. This article extends prior research and examines the effects of birth
      complications and parental involvement on low self-control. Using a sample of
      twin children, the authors find that parental involvement is only weakly and
      inconsistently related to low self-control. On the other hand, although most of
      the birth complications had no appreciable effect on low self-control, anoxia
      (oxygen starvation) emerged as the strongest and most consistent predictor of low
      self-control.

PMID- 15983058
TI  - Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs
      by perturbing the CRM1-dependent mechanism.
AB  - E4orf6 plays an important role in the transportation of cellular and viral mRNAs
      and is known as an oncogene product of adenovirus. Here, we show that E4orf6
      interacts with pp32/leucine-rich acidic nuclear protein (LANP). E4orf6 exports
      pp32/LANP from the nucleus to the cytoplasm with its binding partner, HuR, which
      binds to an AU-rich element (ARE) present within many protooncogene and cytokine
      mRNAs. We found that ARE-mRNAs, such as c-fos, c-myc, and cyclooxygenase-2, were
      also exported to and stabilized in the cytoplasm of E4orf6-expressing cells. The
      oncodomain of E4orf6 was necessary for both binding to pp32/LANP and effect for
      ARE-mRNA. C-fos mRNA was exported together with E4orf6, E1B-55kD, pp32/LANP, and
      HuR proteins. Moreover, inhibition of the CRM1-dependent export pathway failed to
      block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with
      pp32/LANP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export
      pathway.

PMID- 15983059
TI  - TGF-{beta} maintains dormancy of prostatic stem cells in the proximal region of
      ducts.
AB  - We have previously shown that prostatic stem cells are located in the proximal
      region of mouse prostatic ducts. Here, we show that this region responds
      differently to transforming growth factor (TGF)-beta than the distal ductal
      region and that under physiological conditions androgens and TGF-beta are crucial
      overall regulators of prostatic tissue homeostasis. This conclusion is supported
      by the observations showing that high levels of TGF-beta signaling are present in
      the quiescent proximal region of ducts in an androgen-replete animal and that
      cells in this region overexpress Bcl-2, which protects them from apoptosis.
      Moreover, androgen ablation reverses the proximal-distal TGF-beta signaling
      gradient, leading to an increase in TGF-beta signaling in the unprotected distal
      region (low Bcl-2 expression). This reversal of TGF-beta-mediated signaling
      accompanies apoptosis of cells in the distal region and gland involution after
      androgen withdrawal. A physiological TGF-beta signaling gradient (high proximally
      and low distally) and its functional correlates are restored after androgen
      replenishment. In addition to highlighting the regulatory role of androgens and
      TGF-beta, these findings may have important implications for the deregulation of
      the stem cell compartment in the etiology of proliferative prostatic diseases.

PMID- 15983060
TI  - A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes.
AB  - Cells such as fibroblasts and endothelial cells migrate through the coordinated
      responses of discrete integrin-containing focal adhesions and complexes. In
      contrast, little is known about the organization of integrins on the highly
      motile T lymphocyte. We have investigated the distribution, activity, and
      cytoskeletal linkage of the integrin lymphocyte function associated antigen-1
      (LFA-1) on human T lymphocytes migrating on endothelial cells and on ligand
      intercellular adhesion molecule-1 (ICAM-1). The pattern of total LFA-1 varies
      from low expression in the lamellipodia to high expression in the uropod.
      However, high affinity, clustered LFA-1 is restricted to a mid-cell zone that
      remains stable over time and over a range of ICAM-1 densities. Talin is essential
      for the stability and formation of the LFA-1 zone. Disruption of the talin
      integrin link leads to loss of zone integrity and a substantial decrease in speed
      of migration on ICAM-1. This adhesive structure, which differs from the
      previously described integrin-containing attachments displayed by many other cell
      types, we have termed the "focal zone."

PMID- 15983061
TI  - Hypoxia-inducible factor 1{alpha} is a new target of microphthalmia-associated
      transcription factor (MITF) in melanoma cells.
AB  - In melanocytes and melanoma cells alpha-melanocyte stimulating hormone (alpha
      MSH), via the cAMP pathway, elicits a large array of biological responses that
      control melanocyte differentiation and influence melanoma development or
      susceptibility. In this work, we show that cAMP transcriptionally activates Hif1a
      gene in a melanocyte cell-specific manner and increases the expression of a
      functional hypoxia-inducible factor 1alpha (HIF1alpha) protein resulting in a
      stimulation of Vegf expression. Interestingly, we report that the melanocyte
      specific transcription factor, microphthalmia-associated transcription factor
      (MITF), binds to the Hif1a promoter and strongly stimulates its transcriptional
      activity. Further, MITF "silencing" abrogates the cAMP effect on Hif1a
      expression, and overexpression of MITF in human melanoma cells is sufficient to
      stimulate HIF1A mRNA. Our data demonstrate that Hif1a is a new MITF target gene
      and that MITF mediates the cAMP stimulation of Hif1a in melanocytes and melanoma
      cells. Importantly, we provide results demonstrating that HIF1 plays a pro
      survival role in this cell system. We therefore conclude that the alpha-MSH/cAMP
      pathway, using MITF as a signal transducer and HIF1alpha as a target, might
      contribute to melanoma progression.

PMID- 15983062
TI  - Early encounters of a nascent membrane protein: specificity and timing of
      contacts inside and outside the ribosome.
AB  - An unbiased photo-cross-linking approach was used to probe the "molecular path"
      of a growing nascent Escherichia coli inner membrane protein (IMP) from the
      peptidyl transferase center to the surface of the ribosome. The nascent chain was
      initially in proximity to the ribosomal proteins L4 and L22 and subsequently
      contacted L23, which is indicative of progression through the ribosome via the
      main ribosomal tunnel. The signal recognition particle (SRP) started to interact
      with the nascent IMP and to target the ribosome-nascent chain complex to the Sec
      YidC complex in the inner membrane when maximally half of the transmembrane
      domain (TM) was exposed from the ribosomal exit. The combined data suggest a
      flexible tunnel that may accommodate partially folded nascent proteins and parts
      of the SRP and SecY. Intraribosomal contacts of the nascent chain were not
      influenced by the presence of a functional TM in the ribosome.

PMID- 15983063
TI  - Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation
      and transforms the neutrophil granulocyte lineage.
AB  - CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription
      factor that couples lineage commitment to terminal differentiation and cell cycle
      arrest, and is found mutated in 9% of patients who have acute myeloid leukemia
      (AML). We previously showed that mutations which dissociate the ability of C/EBP
      alpha to block cell cycle progression through E2F inhibition from its function as
      a transcriptional activator impair the in vivo development of the neutrophil
      granulocyte and adipose lineages. We now show that such mutations increase the
      capacity of bone marrow (BM) myeloid progenitors to proliferate, and predispose
      mice to a granulocytic myeloproliferative disorder and transformation of the
      myeloid compartment of the BM. Both of these phenotypes were transplantable into
      lethally irradiated recipients. BM transformation was characterized by a block in
      granulocyte differentiation, accumulation of myeloblasts and promyelocytes, and
      expansion of myeloid progenitor populations--all characteristics of AML.
      Circulating myeloblasts and hepatic leukocyte infiltration were observed, but
      thrombocytopenia, anemia, and elevated leukocyte count--normally associated with
      AML-were absent. These results show that disrupting the cell cycle regulatory
      function of C/EBP alpha is sufficient to initiate AML-like transformation of the
      granulocytic lineage, but only partially the peripheral pathology of AML.

PMID- 15983064
TI  - Differential contributions of central and effector memory T cells to recall
      responses.
AB  - Although the absolute number of memory CD8+ T cells established in the spleen
      following antigen encounter remains stable for many years, the relative capacity
      of these cells to mediate recall responses is not known. Here we used a dual
      adoptive transfer approach to demonstrate a progressive increase in the quality
      of memory T cell pools in terms of their ability to proliferate and accumulate at
      effector sites in response to secondary pathogen challenge. This temporal
      increase in efficacy occurred in CD62L lo (effector memory) and CD62L hi (central
      memory) subpopulations, but was most prominent in the CD62L hi subpopulation.
      These data indicate that the contribution of effector memory and central memory T
      cells to the recall response changes substantially over time.

PMID- 15983065
TI  - A multipotent precursor in the thymus maps to the branching point of the T versus
      B lineage decision.
AB  - Hematopoietic precursors continuously colonize the thymus where they give rise
      mainly to T cells, but also to B and dendritic cells. The lineage relationship
      between these three cell types is unclear, and it remains to be determined if
      precursors in the thymus are multipotent, oligopotent, or lineage restricted.
      Resolution of this question necessitates the determination of the clonal
      differentiation potential of the most immature precursors in the thymus. Using a
      CC chemokine receptor 9-enhanced green fluorescent protein knock-in allele like a
      surface marker of unknown function, we identify a multipotent precursor present
      in bone marrow, blood, and thymus. Single cells of this precursor give rise to T,
      B, and dendritic cells. A more differentiated stage of this multipotent precursor
      in the thymus has lost the capacity to generate B but not T, dendritic, and
      myeloid cells. Thus, the newly identified precursor maps to the branching point
      of the T versus B lineage decision in the hematopoietic lineage hierarchy.

PMID- 15983066
TI  - Promiscuous gene expression in thymic epithelial cells is regulated at multiple
      levels.
AB  - The role of central tolerance induction has recently been revised after the
      discovery of promiscuous expression of tissue-restricted self-antigens in the
      thymus. The extent of tissue representation afforded by this mechanism and its
      cellular and molecular regulation are barely defined. Here we show that medullary
      thymic epithelial cells (mTECs) are specialized to express a highly diverse set
      of genes representing essentially all tissues of the body. Most, but not all, of
      these genes are induced in functionally mature CD80(hi) mTECs. Although the
      autoimmune regulator (Aire) is responsible for inducing a large portion of this
      gene pool, numerous tissue-restricted genes are also up-regulated in mature mTECs
      in the absence of Aire. Promiscuously expressed genes tend to colocalize in
      clusters in the genome. Analysis of a particular gene locus revealed expression
      of clustered genes to be contiguous within such a cluster and to encompass both
      Aire-dependent and -independent genes. A role for epigenetic regulation is
      furthermore implied by the selective loss of imprinting of the insulin-like
      growth factor 2 gene in mTECs. Our data document a remarkable cellular and
      molecular specialization of the thymic stroma in order to mimic the transcriptome
      of multiple peripheral tissues and, thus, maximize the scope of central self
      tolerance.

PMID- 15983067
TI  - Contrasting models of promiscuous gene expression by thymic epithelium.
AB  - Medullary thymic epithelial cells (mTECs) express a broad spectrum of tissue-
      restricted self-antigens (TRAs), which are required for the development of
      central tolerance. A new study suggests that TRA expression is a specialized
      property of terminally differentiated mTECs. However, as discussed here, an
      alternative model-whereby TRA expression is regulated by conserved developmental
      programs active in developing mTECs-may be equally plausible.

PMID- 15983068
TI  - Many roads, one destination for T cell progenitors.
AB  - The thymus manufactures new T cells throughout life but contains no self-renewing
      potential. Instead, replenishment depends on recruitment of bone marrow-derived
      progenitors that circulate in the blood. Attempts to identify thymic-homing
      progenitors, and to assess the degree to which they are precommitted to the T
      cell lineage, have led to complex and sometimes conflicting results. As described
      here, this probably reflects the existence of multiple distinct types of T cell
      lineage progenitors as well as differences in individual experimental approaches.

PMID- 15983069
TI  - Use of productivity and financial indicators for monitoring performance in
      academic radiology departments: U.S. nationwide survey.
AB  - PURPOSE: To determine how productivity- and finance-related indicators are used
      by radiology departments to evaluate departmental performance. MATERIALS AND
      METHODS: The study met the criteria to be exempt from institutional review board
      approval. All subjects were informed of the purpose of the study and that their
      questionnaire responses would be kept confidential. For the study, a survey was
      sent to 132 members of the Society of Chairmen of Academic Radiology Departments
      (SCARD) nationwide. The survey was designed to (a) assess organizational
      information about hospital and radiology departments, (b) determine the types and
      mean numbers of productivity and financial indicators used by radiology
      departments, (c) determine how these indicators are used to influence
      departmental productivity, and (d) assess the reference-standard goals with which
      each indicator value was compared. A total of 77 variables were studied. Summary
      statistics, Spearman rank correlation coefficient, and chi2 analyses were
      performed. RESULTS: The response rate was 42% (55 of 132 surveyed SCARD members).
      The mean number of productivity indicators used by radiology departments was 4.55
      +/- 2.56 (standard deviation), while the mean number of financial indicators used
      was 2.89 +/- 1.99. Twenty-two (40%) of the 55 responding departments used
      productivity indicators to monitor and provide feedback to radiologists, hospital
      leaders, and technical staff members for improved productivity, but only 11 (20%)
      departments used these indicators to compare personnel performances against
      specific productivity standards. The most frequent goal (of seven [13%]
      responding departments) of using the indicators was to increase the examination
      volume from the previous year by 5%-10%. CONCLUSION: Academic radiology
      departments across the United States do not use a standardized set of
      productivity and financial indicators to measure departmental performance.
      Examination volume is the most frequently used productivity indicator, whereas
      general expenses are commonly used as indicators of financial status.

PMID- 15983070
TI  - Prostate cancer: precision of integrating functional MR imaging with radiation
      therapy treatment by using fiducial gold markers.
AB  - The use of intensity-modulated radiation therapy for treatment of dominant
      intraprostatic lesions may require integration of functional magnetic resonance
      (MR) imaging with treatment-planning computed tomography (CT). The purpose of
      this study was to compare prospectively the landmark and iterative closest point
      methods for registration of CT and MR images of the prostate gland after
      placement of fiducial markers. The study was approved by the institutional ethics
      review board, and informed consent was obtained. CT and MR images were registered
      by using fiducial gold markers that were inserted into the prostate. Two image
      registration methods--a commonly available landmark method and dedicated
      iterative closest point method--were compared. Precision was assessed for a data
      set of 21 patients by using five operators. Precision of the iterative closest
      point method (1.1 mm) was significantly better (P < .01) than that of the
      landmark method (2.0 mm). Furthermore, a method is described by which multimodal
      MR imaging data are reduced into a single interpreted volume that, after
      registration, can be incorporated into treatment planning.

PMID- 15983071
TI  - Detection of simulated lesions on data-compressed digital mammograms.
AB  - PURPOSE: To evaluate retrospectively the effect of a wavelet-based compression
      method on the detection of simulated masses of various sizes and clustered
      microcalcifications on data-compressed digital mammograms. MATERIALS AND METHODS:
      The images used in this study were acquired with institutional review board
      approval and patient informed consent, both of which allowed subsequent image
      data analysis. Patient identification was removed from images, and the study
      complied with requirements of the Health Insurance Portability and Accountability
      Act. Masses 3, 6, and 8 mm in diameter were analytically simulated and added to
      clinical mammographic backgrounds. In addition, microcalcifications were
      extracted from a clinical mammogram and hybridized with simulated
      microcalcifications for use in this study. Image compression conditions of 1:1,
      15:1, and 30:1 were investigated. Observer responses were recorded with a six
      point rating scale, and receiver operating characteristic (ROC) analysis was
      performed. In addition, two well-established numeric observer models were used to
      study the effect of image compression under the same compression conditions as
      were used with human observers. Analysis of variance was performed after observer
      adjustment to compare the mean values for area under the ROC curve (A(z)) across
      the three compression levels for the masses and microcalcification clusters.
      RESULTS: The results of the study indicated no significant differences in the
      A(z) values for masses with the compression conditions investigated. For images
      of microcalcifications, there were significant differences in A(z) values between
      compression ratios of 1:1 and 30:1 (P = .0005) and of 15:1 and 30:1 (P = .004);
      the difference between compression ratios of 1:1 and 15:1 was nonsignificant (P =
      .053). The observer models and human observers exhibited similar trends in
      detection of the masses investigated in this study. CONCLUSION: Detection of
      simulated masses was not affected by the compression method with the conditions
      used in this study, while the detection of microcalcifications was significantly
      reduced with a compression ratio of more than 15:1.

PMID- 15983072
TI  - Association between compliance with methodological standards of diagnostic
      research and reported test accuracy: meta-analysis of focused assessment of US
      for trauma.
AB  - PURPOSE: To study whether compliance with methodological standards affected the
      reported accuracy of screening ultrasonography (US) for trauma. MATERIALS AND
      METHODS: Meta-analysis was conducted of prospective investigations in which US
      was compared with any diagnostic reference test in patients with suspected
      abdominal injury. Reports were retrieved from electronic databases without
      language restrictions; added information was gained with manual search. Two
      reviewers independently assessed methodological rigor by using 27 items contained
      in the Standards for Reporting of Diagnostic Accuracy (STARD) checklist and the
      Quality Assessment of Studies of Diagnostic Accuracy included in Systematic
      Reviews (QUADAS) instrument. Inconsistencies were resolved by means of consensus.
      Summary receiver operating characteristics and random-effects meta-regression
      were used to model the effect of methodological standards and other study
      features on US accuracy. RESULTS: A total of 62 trials, which included a total of
      18,167 participants, were eligible for meta-analysis. The average proportion of
      men or boys was 71.7%, the mean age was 30.6 years +/- 10.8 (standard deviation),
      and the mean injury severity score was 16.7 +/- 8.3. The prevalence of abdominal
      trauma was 25.1% (95% confidence interval [CI]: 21.1%, 29.1%). Pooled overall
      sensitivity and specificity of US were 78.9% (95% CI: 74.9%, 82.9%) and 99.2%
      (95% CI: 99.0%, 99.4%), respectively. Varying end points (hemoperitoneum or organ
      damage) did not change these results. US accuracy was much lower in children
      (sensitivity, 57.9%; specificity, 94.3%). Strong heterogeneity was observed in
      sensitivity, whereas specificity remained constant across trials. There was
      evidence of publication bias. Initial interobserver agreement with methodological
      standards ranged from poor (kappa = 0.03, independent verification of US
      findings) to perfect (kappa = 1.00, sufficiently short interval between US and
      reference test). By consensus, studies fulfilled a median of 13 methodological
      criteria (range, five to 20 criteria). In investigations that lacked individual
      methodological standards, researchers overestimated pooled sensitivity, with
      predicted differences of 9%-18%. The use of a single reference test,
      specification of the number of excluded patients, and calculation of CIs
      independently contributed to predicted sensitivity in a multivariate model. In 16
      investigations (1309 subjects), a single reference test was used, which provided
      a combined sensitivity of 66.0% (95% CI: 56.2%, 75.8%). CONCLUSION: Bias-adjusted
      sensitivity of screening US for trauma is low. Adherence to methodological
      standards included in appraisal instruments like STARD and QUADAS is crucial to
      obtain valid estimates of test accuracy.

PMID- 15983073
TI  - Idiopathic eosinophilic esophagitis in adults: the ringed esophagus.
AB  - PURPOSE: To retrospectively assess the findings of idiopathic eosinophilic
      esophagitis (IEE) at barium studies and determine the frequency of the ringed
      esophagus in patients with this condition. MATERIALS AND METHODS: The
      institutional review board approved all aspects of this retrospective study and
      did not require informed consent from patients whose records were included in the
      study. The study was compliant with the Health Insurance Portability and
      Accountability Act. A review of the pathology and radiology databases at the
      authors' institution revealed 14 patients (11 men and three women; mean age, 41.3
      years) with IEE (defined as more than 20 eosinophils per high-power field in
      biopsy specimens) who had undergone barium studies and endoscopy. The radiographs
      were reviewed for strictures, esophagitis, or other abnormalities. The endoscopic
      reports, clinical records, and laboratory data were also reviewed and compared
      with the radiographic findings. RESULTS: Seven of the 14 patients (50%) had a
      history of allergies, and two of nine patients with complete blood cell counts
      (22%) had peripheral eosinophilia. Thirteen patients (93%) had dysphagia, six
      (43%) had food impactions, and six (43%) had reflux symptoms. Ten patients (71%)
      had a total of 11 strictures at barium studies (two in the upper part of the
      esophagus, two in the middle part, three in the distal part, one in the middle
      and distal parts, and three at the gastroesophageal junction). The strictures had
      a mean length of 5.1 cm. In seven patients (50%), the strictures contained
      multiple fixed ringlike indentations that produced a ringed esophagus. The
      ringlike indentations appeared as multiple, fixed, closely spaced, concentric
      rings traversing the stricture. Four patients (28%) had esophagitis. Of 13
      patients who underwent recumbent imaging, 10 (77%) had hiatal hernias and nine
      (69%) had reflux. Eight of the 10 patients (80%) with strictures underwent
      endoscopic dilation procedures, which resulted in only temporary relief of
      dysphagia. CONCLUSION: The findings suggest that most patients with IEE have
      esophageal strictures, often with distinctive ringlike indentations that produce
      a ringed esophagus.

PMID- 15983074
TI  - Interpretation of chest radiographs in infants with cough and fever.
AB  - An understanding of the appearance of the infant chest radiograph requires an
      understanding of the anatomy and the physiologic, immunologic, and pathologic
      processes in the infant's chest. The authors describe the features of the infant
      chest that most influence the appearance of the chest radiograph in infants with
      cough and fever. They discuss why confusion sometimes occurs when radiology
      residents and general radiologists familiar with adult chest radiographs first
      evaluate the infant chest radiograph. The radiographic appearance of acute
      inflammation does not look the same in infants as it does in older children and
      adults. The hallmark of inflammatory lung disease in the infant chest is air
      trapping on the chest radiograph.

PMID- 15983078
TI  - Myocardial contusion injury: redefining the diagnostic algorithm.
AB  - Myocardial contusion injury (MCI) is a complication of blunt thoracic trauma,
      which may occur at relatively low velocities. MCI may also occur from chest
      compressions during cardiopulmonary resuscitation. We review the clinical
      pathology, diagnostic tools, and treatment for MCI.

PMID- 15983079
TI  - No frills management of epistaxis.
AB  - Epistaxis is a common, potentially life threatening, emergency but first line
      medical staff are often not adequately trained in its management. This paper
      presents an illustrated step by step guide to the management of epistaxis by
      junior doctors in the emergency department.

PMID- 15983080
TI  - Emergency department management of mild traumatic brain injury in the USA.
AB  - OBJECTIVE: To describe the emergency department (ED) management of isolated mild
      traumatic brain injury (TBI) in the USA and to examine variation in care across
      age and insurance types. METHODS: A secondary analysis of ED visits for isolated
      mild TBI in the National Hospital Ambulatory Medical Care Survey 1998-2000 was
      performed. Mild TBI was defined by International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9) codes for skull fracture, concussion,
      intracranial injury (unspecified), and head injury (unspecified). Available ED
      care variables were analysed by patient age and insurance categories using
      multivariate logistic regression. RESULTS: The incidence of isolated mild TBI
      cases attending ED was 153,296 per year, or 56.4/100,000 people. Of the patients
      with isolated mild TBI, 44.3% underwent computed tomography, 23.9% underwent
      other non-extremity, non-chest x rays, 17.1% received wound care and 14.1%
      received intravenous fluids. However, only 43.8% had an assessment of pain. Of
      those with documented pain, only 45.5% received analgesics in the ED. Nearly 38%
      were discharged without recommendations for specific follow up. Several aspects
      of ED care varied by age but not by insurance type. CONCLUSION: Substantial ED
      resources are devoted to the care of isolated mild TBI. The present study
      identified deficiencies in and variation around several important aspects of ED
      care. The development of guidelines specific for mild TBI could reduce variation
      and improve emergency care for this injury.

PMID- 15983081
TI  - Preoperative management of the amputated limb.
AB  - Little literature exists on storage and preparation of an amputated limb prior to
      transfer to a reconstructive plastic surgical unit for possible
      macroreplantation. This paper describes practical measures used to prolong
      ischaemia time allowing macroreplantation, tissue harvesting, or fashioning of a
      useful stump. A simple protocol is used to summarise these points.

PMID- 15983082
TI  - Prevalence of victims of violence admitted to an emergency department.
AB  - OBJECTIVE: To collect data on the consultation frequency and demographic profile
      of victims of violence attending an emergency department (ED) in Switzerland.
      METHODS: We undertook screening of all admitted adult patients (>16 years) in the
      ED of the CHUV, Lausanne, Switzerland, over a 1 month period, using a modified
      version of the Partner Violence Screen questionnaire. Exclusionary criteria were:
      life threatening injury (National Advisory Committee on Aeronautics score > or
      =4), or inability to understand or speak French, to give oral informed consent,
      or to be questioned without a family member or accompanying person being present.
      Data were collected on history of physical and/or psychological violence during
      the previous 12 months, the type of violence experienced by the patient, and if
      violence was the reason for the current consultation. Sociodemographic data were
      obtained from the registration documents. RESULTS: The final sample consisted of
      1602 patients (participation rate of 77.2%), with a refusal rate of 1.1%.
      Violence during the past 12 months was reported by 11.4% of patients. Of the
      total sample, 25% stated that violence was the reason for the current
      consultation; of these, 95% of patients were confirmed as victims of violence by
      the ED physicians. Patients reporting violence were more likely to be young and
      separated from their partner. Men were more likely to be victims of public
      violence and women more commonly victims of domestic violence. CONCLUSIONS: Based
      on this monthly prevalence rate, we estimate that over 3000 adults affected by
      violence consult our ED per annum. This underlines the importance of the problem
      and the need to address it. Health services organisations should establish
      measures to improve quality of care for victims. Guidelines and educational
      programmes for nurses and physicians should be developed in order to enhance
      providers' skills and basic knowledge of all types of violence, how to recognise
      and interact appropriately with victims, and where to refer these patients for
      follow up care in their local networks.

PMID- 15983083
TI  - Detection of chest pain of non-cardiac origin at the emergency room by a new non
      invasive device avoiding unnecessary admission to hospital.
AB  - Recent advances in the treatment of acute coronary syndromes has raised awareness
      that prompt presentation for chest pain may be life saving. Most patients
      presenting with chest discomfort have a non-ischaemic ECG on presentation, but
      are routinely admitted to hospital because of diagnostic uncertainty for occult
      MI or ischaemia. We tested a new non-invasive device that measures central aortic
      pressure changes (dP/dtejc): an accepted index of myocardial performance that
      could be added to the diagnostic triage of ischaemia in the ER avoiding
      unnecessary admissions. We followed 85 patients presenting at the ER with acute
      chest pain. In 72 patients, negative ECG and myocardial enzyme dynamics ruled out
      coronary origin during the first 24 h after admission. In 8 of the 72 patients,
      coronary catheterisation found normal coronary arteries. In this group, average
      dP/dtejc was 163 (range 92-232). In 35 patients in whom the new non-invasive
      cardiac performance index dP/dtejc was above a threshold of >150, acute MI was
      ruled out. In 13 patients, acute chest pain had coronary origin confirmed by ECG
      and/or positive enzymes. The average dP/dtejc in this group was 117 (range 61
      149). The dP/dtejc values were found to be significantly higher in patients
      without acute MI (p<0.001). Preliminary findings suggest that nearly 40% of
      patients presenting with acute chest pain could be spared the risks and costs of
      unnecessary hospital admission and more invasive cardiac testing by simply adding
      a easy to use, immediately obtained, test to the diagnostic protocol, and using a
      threshold of dP/dtejc>150 to rule out heart attack.

PMID- 15983084
TI  - Continuous end-tidal carbon dioxide monitoring for confirmation of endotracheal
      tube placement is neither widely available nor consistently applied by emergency
      physicians.
AB  - OBJECTIVES: To determine the availability of end-tidal CO2 measurement in
      confirmation of endotracheal tube placement in the non-arrest patient, and to
      assess its use in academic and non-academic emergency departments. METHODS:
      Emergency physicians in the USA were surveyed by mail in the beginning of the
      year 2000 regarding availability at their institution of both
      colorimetric/qualitative and quantitative end-tidal CO2 capnography, frequency of
      use in their own practice, and descriptor of their hospital (academic, community
      teaching, and community non-teaching). Additionally, data were obtained from the
      National Emergency Airway Registry 97 series (NEAR) about how many intubations
      used this method of confirmation. NEAR site coordinators were surveyed as well.
      RESULTS: Of 1000 surveys, 550 were returned (55%). Colorimetric technology
      existed in 77% of respondents' hospitals (n = 421); 25% of respondents (n = 138)
      had continuous monitoring capability. Physicians practising at academic hospitals
      were more likely to have continuous monitoring (36%; n = 196) than community
      teaching institutions (32%; n = 173) and non-teaching centres (18%; n = 100)
      (p<0.001). Among physicians who had this technology available, only 14% (n = 19)
      "always" used it in non-arrest intubations; 57% "rarely" or "never" employed it
      (n = 75). Among NEAR centres (institutions committed to monitoring current airway
      practices) only 12% of 6009 (n = 716) intubations used continuous end-tidal CO2
      measurement. Of these practitioners, only 40% "always" used it (n = 6/15) (83%
      response rate (n = 29/35)). CONCLUSIONS: Despite recommendations from national
      organisations that endorse continuous monitoring of end-tidal CO2 for confirming
      endotracheal tube placement, it is neither widely available nor consistently
      applied.

PMID- 15983086
TI  - Patient self discharge from the emergency department: who is at risk?
AB  - OBJECTIVES: To identify the number of patients who take their own discharge, to
      review how their competence to make the decision to refuse treatment was being
      assessed and managed, and to quantify the medical risk to these patients.
      METHODS: A retrospective review of all case notes coded as "self discharge" for a
      three month period. A second cohort was reviewed following the introduction of a
      new self discharge proforma. RESULTS: Patients who self discharge represented
      0.5% of the total number of attendances, and those who "did not wait" represented
      a further 11%. Fifty percent were under the influence of drugs or alcohol. Sixty
      three percent refused admission, 24% refused treatment, and 13% refused medical
      assessment. In the first audit, assessment of capacity was documented in 0%, 58%
      signed a self discharge form, 25% were reviewed by a doctor prior to leaving, and
      31% left the department without the staff's knowledge. In the second audit,
      capacity was documented in 80%, 80% signed the new self discharge form, 41% were
      reviewed by a doctor prior to leaving, and 0% left the department without being
      reviewed. DISCUSSION: Self discharge may be a significant risk to both the
      patient and the hospital trust. Departments should review their own systems for
      assessing and managing this patient group. Further work looking at the
      consequences of self discharge is required.

PMID- 15983085
TI  - Medical experience of a university hospital in Turkey after the 1999 Marmara
      earthquake.
AB  - OBJECTIVES: This study aimed to provide an overview of morbidity and mortality
      among patients admitted to the Hospital of the Medicine Faculty of Uludag
      University, Bursa, Turkey, after the 1999 Marmara earthquake. METHODS:
      Retrospective analysis of the medical records of 645 earthquake victims.
      Patients' demographic data, diagnosis, dispositions, and prognosis were reviewed.
      RESULTS: A total of 330 patients with earthquake related injuries and illness
      admitted to our hospital were included and divided into three main groups: crush
      syndrome (n = 110), vital organ injuries (n = 57), and non-traumatic but
      earthquake related illness (n = 55). Seventy seven per cent of patients were
      hospitalised during the first three days after the earthquake. The rate of
      mortality associated with the crush syndrome, vital organ injury, and non
      traumatic medical problems was 21% (23/110), 17.5% (10/57), and 9% (5/55),
      respectively. The overall mortality rate was 8% (50/645). CONCLUSIONS: In the
      first 24-48 hours after a major earthquake, hospital emergency departments are
      flooded with large numbers of patients. Among this patient load, those patients
      with crush syndrome or vital organ injuries are particularly at risk. Proper
      triage and prompt treatment of these seriously injured earthquake victims may
      decrease morbidity and mortality. It is hoped that this review of the challenges
      met after the Marmara earthquake and the lessons learned will be of use to
      emergency department physicians as well as hospital emergency planners in
      preparing for future natural disasters.

PMID- 15983087
TI  - Best evidence topic report. Transthoracic ultrasonography to diagnose
      pneumothorax in trauma.
AB  - A short cut review was carried out to establish whether transthoracic ultrasound
      can be used to diagnose pneumothoraces in trauma patients. A total of 46 papers
      were found using the reported search, of which four represented the best evidence
      to answer the clinical question. The author, date and country of publication,
      patient group studied, study type, relevant outcomes, results, and study
      weaknesses of these best papers are tabulated. A clinical bottom line is stated.

PMID- 15983089
TI  - Best evidence topic report. Do we need to give steroids in children with Bell's
      palsy?
AB  - A short cut review was carried out to establish whether steroids are indicated in
      children presenting with Bell's palsy. A total of 60 papers were found using the
      reported search, of which three represented the best evidence to answer the
      clinical question. The author, date and country of publication, patient group
      studied, study type, relevant outcomes, results, and study weaknesses of these
      best papers are tabulated. A clinical bottom line is stated.

PMID- 15983090
TI  - Best evidence topic report. Early mobilisation for volar plate avulsion
      fractures.

PMID- 15983091
TI  - Best evidence topic report. Topical anaesthetic versus lidocaine infiltration to
      allow closure of skin wounds in children.
AB  - A short cut review was carried out to establish whether topical anaesthetics are
      an acceptable alternative to lidocaine infiltration in children. A total of 54
      papers were found using the reported search, of which seven represented the best
      evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results, and
      study weaknesses of these best papers are tabulated. A clinical bottom line is
      stated.

PMID- 15983092
TI  - SOCRATES 9 (synopsis of Cochrane Reviews applicable to emergency services).

PMID- 15983093
TI  - Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A
      randomised controlled trial.
AB  - OBJECTIVE: To investigate whether 10% dextrose given in 5 g (50 ml) aliquots is
      more effective than 50% dextrose given in 5 g (10 ml) aliquots in the treatment
      of out of hospital hypoglycaemia. DESIGN: Randomised controlled trial. SETTING:
      Out of hospital patients attended by paramedics from a large UK ambulance
      service. PARTICIPANTS: 51 unresponsive adult patients with blood glucose levels <
      or = 4 mmol/l. INTERVENTION: 5 g (50 ml) intravenous aliquots of 10% dextrose or
      5 g (10 ml) intravenous aliquots of 50% dextrose to a maximum dose of 25 g. MAIN
      OUTCOME MEASURES: To compare for each dextrose concentration the time to achieve
      a Glasgow Coma Scale (GCS) score of 15, and the dose required to obtain a blood
      glucose level of > or = 4.5 mmol/l. RESULTS: There were no statistically
      significant differences between the groups with regard to age or sex, median
      pretreatment GCS, pretreatment blood glucose level, or proportion of patients
      with insulin dependent diabetes. Following treatment, there were no statistically
      significant differences in median time to recovery (8 minutes), median post
      treatment GCS, or number of subjects experiencing a further hypoglycaemic episode
      within 24 hours (four per group). The median total dose of dextrose administered
      was significantly less with the 10% concentration (10% = 10 g, 50% = 25 g, p <
      0.001) and median post-treatment blood sugar levels were also significantly lower
      (10% = 6.2 mmol/l and 50% = 9.4 mmol/l, p = 0.003). There were no reports of
      extravasation injuries in either group. CONCLUSIONS: Dextrose 10% delivered in 5
      g (50 ml) aliquots is administered in smaller doses than dextrose 50% delivered
      in 5 g/10 ml aliquots, resulting in lower post-treatment blood glucose levels. We
      therefore recommend it as the intravenous treatment of choice for adult
      hypoglycaemia.

PMID- 15983094
TI  - Competence in prehospital care: evolving concepts.
AB  - Competence based training and assessment has become central to education and
      training for healthcare professionals. There continues to be uncertainty about
      the meaning of competence and how the principles underpinning competence based
      training and assessment can be applied to evolving subspecialty and
      multidisciplinary areas such as prehospital care. Considerable development work
      has been undertaken on a national level with the creation of a Competence
      Framework for Emergency Care. This article explores the concepts of competence,
      defines the terminology, and describes the role of a competence framework in
      education and training.

PMID- 15983095
TI  - Spontaneous fulminant gas gangrene.
AB  - Gas gangrene is a rare condition, usually associated with contaminated traumatic
      injuries. It carries a high rate of mortality and morbidity. A number of studies
      have implicated non-traumatic gas gangrene and colonic neoplasia. This paper
      reports a patient who presented spontaneously with Clostridium septicum gas
      gangrene and an occult caecal carcinoma.

PMID- 15983096
TI  - Delayed presentation of traumatic ventricular septal defect and mitral leaflet
      perforation.
AB  - A case of intracardiac stabbing is reported. The victim sustained injuries
      disproportionate to his initial presentation. These included a ventricular septal
      defect and mitral valve leaflet perforation. The need for immediate referral to a
      cardiothoracic unit and the importance of the use of echocardiography is
      stressed. This enables the safest and most appropriate management of potentially
      lethal injuries.

PMID- 15983097
TI  - Rectus sheath haematoma: 'a diagnostic dilemma ?'.

PMID- 15983098
TI  - Accidental human poisoning with a veterinary tranquilliser.

PMID- 15983099
TI  - Unusual abdominal complication of rib fracture: a case report and review of
      literature.

PMID- 15983100
TI  - Coincidental deficiency of the posterior arch of the atlas and thalassaemia
      minor: possible pitfalls in a trauma victim.
AB  - Congenital abnormalities of the cervical spine are rare findings in trauma
      victims. Deficiency of the posterior arch of the atlas and coincidental
      thalassaemia minor are even more unusual. This case report is about a young
      female trauma victim with both abnormalities, a combination that has previously
      not been described in literature. The classification, as proposed by Currarino et
      al in 1994, and the importance of being aware of these abnormalities are
      discussed.

PMID- 15983101
TI  - Primary gradient defect distal renal tubular acidosis presenting as hypokalaemic
      periodic paralysis.
AB  - A 45 year old man presented with recurrent hypokalaemic paralysis. Laboratory
      investigations revealed renal tubular acidosis as the cause of the hypokalaemia,
      and dynamic tubular studies suggested a gradient defect as the underlying cause.
      The patient had associated dextrocardia. To our knowledge, this is the first
      report of this condition.

PMID- 15983102
TI  - Fit for the road?

PMID- 15983103
TI  - Unusual complication of an organophosphate poisoning.

PMID- 15983104
TI  - A load of hot air.

PMID- 15983106
TI  - Variables differentiating singly and multiply victimized youth: results from the
      National Survey of Adolescents and implications for secondary prevention.
AB  - The authors examined variables differentiating singly and multiply victimized
      youth with a national household probability sample of 4,023 adolescents. Youth
      endorsing one episode (i.e., one incident or series of repeat incidents) of
      sexual or physical assault were classified as singly victimized (n = 435).
      Multiply victimized youth were those who endorsed multiple discrete episodes of
      sexual or physical assault and both sexual and physical assault (n = 396). For
      boys, heightened risk of multiple victimization was associated with family
      alcohol problems, Native American race, and earlier age at assault onset. For
      girls, increased multiple victimization risk was associated with family alcohol
      problems, older current age, and several characteristics of the initial assault
      episode-earlier age at onset, acquaintance perpetrator, chronicity, perceived
      life threat, and injury. Findings imply that secondary prevention programs may be
      strengthened by broadening risk-reduction strategies to address a greater range
      of victimization experiences. Additional implications for secondary prevention
      are discussed.

PMID- 15983107
TI  - Police involvement in child protective services investigations: literature review
      and secondary data analysis.
AB  - This article examines the relationship of police and child protective services
      (CPS) coinvolvement to the outcomes of child maltreatment investigations. It
      reviews practice and empirical literature and conducts a secondary analysis of a
      national CPS data set. Most sources argue that coordination of the two agencies
      improves investigations and benefits children and families. Yet, sources also
      report friction between these agencies, interference with each other's job, and
      concerns that police involvement increases child removal. In the CPS case data,
      allegations were more likely to be judged credible when police also investigated
      and families were also more likely to receive various services. For neglect
      cases, multi-disciplinary decision making, but not police involvement per se, was
      linked to child removal. Across studies, police do not appear to hinder CPS
      effectiveness and may actually promote it. Their investigations should be
      coordinated in every community.

PMID- 15983108
TI  - Child maltreatment prevention priorities at the Centers for Disease Control and
      Prevention.
AB  - The Division of Violence Prevention at Centers for Disease Control and
      Prevention's (CDC) National Center for Injury Prevention and Control has had a
      long-standing interest in the prevention of child maltreatment. The nation's
      public health agency, CDC, seeks to focus the public health perspective on the
      problem of child maltreatment and to promote science-based practice in the field.
      Since 1999, CDC has developed research priorities to address the prevention of
      child maltreatment. Described here is a brief rationale for applying a public
      health approach to child maltreatment and a discussion of the priority-setting
      process, priorities in each of four areas of the public health model, and some of
      CDC's current child maltreatment prevention activities.

PMID- 15983109
TI  - Nonforcible Internet-related sex crimes with adolescent victims: prosecution
      issues and outcomes.
AB  - Law enforcement officials and the public are said to hold the stereotype that it
      is difficult to prosecute cases involving nonforcible sex crimes with willing
      adolescent victims. The authors examine prosecution outcomes in nonforcible
      Internet-related sex crimes with adolescent victims and extra-familial adult
      defendants. Data are from a national sample of law enforcement officers and
      prosecutors (N = 77). Most (91%) of the defendants are convicted, usually via a
      guilty plea (77%). Results show that even when victim cooperation is lacking or
      victims willingly engage in sexual activity, defendants are convicted. A small
      group of defendants are not convicted, and certain conditions appear to
      contribute to this, including victims' untruthfulness, defendants giving victims
      illegal drugs or alcohol, and lack of a confession from the defendant. Most
      defendants, however, are sentenced to incarceration and required to register as
      sex offenders. The findings show promise for holding defendants accountable for
      this type of crime.

PMID- 15983110
TI  - Attitudes mediate the association between childhood disciplinary history and
      disciplinary responses.
AB  - According to recent estimates, childhood abuse victims are at 12 times higher
      risk for child abuse perpetration than those without such abusive histories. This
      study focused on delineation of the mechanisms by which intergenerational
      patterns of abuse may occur and, in particular, the role that disciplinary
      attitudes may play in mediating the relation between disciplinary history and
      risk for abusive parenting. Participants (n = 459) completed a series of
      questionnaires to assess childhood history, disciplinary attitudes, and
      disciplinary practices. Structural equation modeling indicated that the
      association between disciplinary history and disciplinary responses was partially
      mediated by attitudes, with more than half of the association between history and
      responses accounted for by attitudes. These findings support the need for
      interventions to focus on attitudinal change when attempting to reduce risk for
      perpetration among those with histories of abuse.

PMID- 15983111
TI  - Corporal punishment and the growth trajectory of children's antisocial behavior.
AB  - Despite considerable research, the relationship between corporal punishment and
      antisocial behavior is unclear. This analysis examined (a) the functional form of
      this relationship, (b) the correlation of initial antisocial behavior and changes
      in antisocial behavior, (c) differences in the relationship of corporal
      punishment and antisocial behavior by race, and (d) whether this relationship
      could be accounted for by unmeasured characteristics of children and their
      families. Data from 6,912 children in the National Longitudinal Survey of Youth
      were analyzed using hierarchical linear models. Findings suggested that corporal
      punishment has a relationship with children's initial antisocial behavior and
      with changes in antisocial behavior. No evidence was found for differences in the
      effect of corporal punishment across racial groups. The relationship between
      corporal punishment and antisocial behavior persists even when accounting for
      unmeasured time invariant characteristics of children and families. The findings
      suggest that corporal punishment is not a preferable technique for disciplining
      children.

PMID- 15983112
TI  - The socialization of emotional understanding: a comparison of neglectful and
      nonneglectful mothers and their children.
AB  - This study investigated the influence of maternal socialization (i.e., maternal
      support, discussion of emotion, negative affect) on children's emotional
      understanding in 24 neglectful mother-child dyads and a matched control group.
      Mothers and children were administered an interaction task. Mothers were also
      assessed for negative emotional experience, and children were assessed for
      emotional understanding and expectations of maternal support. Findings indicated
      that neglectful mothers, compared with nonneglectful mothers, provided less
      support in response to their children's emotional displays, engaged in less
      emotional discussion, and reported more negative emotion. As well, neglected
      children demonstrated lower levels of emotional understanding than nonmaltreated
      children. Further, maternal support mediated the relation between neglect and
      children's emotional understanding. Findings are discussed from the functionalist
      approach to emotional development, emphasizing the importance of social context
      and socialization on children's emotional understanding.

PMID- 15983113
TI  - ATP-sensitive K+-channel subunits on the mitochondria and endoplasmic reticulum
      of rat cardiomyocytes.
AB  - ATP-sensitive K(+) (K(ATP)) channel subunits on the subcellular structures of rat
      cardiomyocytes were studied with antibodies against Kir6.1 and Kir6.2. According
      to the results of Western blot analysis, Kir6.1 was strongly expressed in
      mitochondrial and microsome fractions, and faintly expressed in cell membrane
      fraction, whereas Kir6.2 was mainly expressed in the microsome fraction and
      weakly in cell membrane and mitochondrial fractions. Immunohistochemistry showed
      that Kir6.1 and Kir6.2 were expressed in the endocardium, atrial and ventricular
      myocardium, and in vascular smooth muscles. Immunoelectron microscopy revealed
      that Kir6.1 immunoreactivity was mainly localized in the mitochondria, whereas
      Kir6.2 immunoreactivity was mainly localized in the endoplasmic reticulum and a
      few in the mitochondria. Both Kir6.1 and Kir6.2 are candidates of mitochondrial
      K(ATP) channel subunits. The data obtained in this study will be useful for
      analyzing the composition of K(ATP) channels of cardiomyocytes and help to
      understanding the cardioprotective role of K(ATP) channels during heart ischemia.

PMID- 15983114
TI  - Cell type-specific expression of beta-carotene 9',10'-monooxygenase in human
      tissues.
AB  - The symmetrically cleaving beta-carotene 15,15'-monooxygenase (BCO1) catalyzes
      the first step in the conversion of provitamin A carotenoids to vitamin A in the
      mucosa of the small intestine. This enzyme is also expressed in epithelia in a
      variety of extraintestinal tissues. The newly discovered beta-carotene 9',10'
      monooxygenase (BCO2) catalyzes asymmetric cleavage of carotenoids. To gain some
      insight into the physiological role of BCO2, we determined the expression pattern
      of BCO2 mRNA and protein in human tissues. By immunohistochemical analysis it was
      revealed that BCO2 was detected in cell types that are known to express BCO1,
      such as epithelial cells in the mucosa of small intestine and stomach,
      parenchymal cells in liver, Leydig and Sertoli cells in testis, kidney tubules,
      adrenal gland, exocrine pancreas, and retinal pigment epithelium and ciliary body
      pigment epithelia in the eye. BCO2 was uniquely detected in cardiac and skeletal
      muscle cells, prostate and endometrial connective tissue, and endocrine pancreas.
      The finding that the BCO2 enzyme was expressed in some tissues and cell types
      that are not sensitive to vitamin A deficiency and where no BCO1 has been
      detected suggests that BCO2 may also be involved in biological processes other
      than vitamin A synthesis.

PMID- 15983115
TI  - Expression of versican and ADAMTS1, 4, and 5 during bone development in the rat
      mandible and hind limb.
AB  - Extracellular matrix (ECM) remodeling is achieved by both production and
      degradation of ECM molecules during bone development. ADAMTS (a disintegrin and
      metalloprotease with thrombospondin type 1 motifs) constitutes a family of
      extracellular proteases which are implicated in cleaving the protein versican.
      The present study was designed to investigate the expression of versican and
      ADAMTS1, 4, and 5 mRNA during bone development in rat mandibles and hind limbs by
      RT-PCR and in situ hybridization. Versican was localized by immunohistochemistry.
      The process of bone development from day 14 postcoitum through week 6 postnatum
      was divided into the beginning of osteogenesis, woven bone, and lamellar bone
      stages. Versican protein was abundant in the woven bone matrix, but decreased in
      the lamellar bone matrix. Versican mRNA was prominent in some osteoblasts with
      corresponding localization of the cognate protein. The temporal and spatial mRNA
      expression pattern of ADAMTS1, 4, and 5 was comparable to that of versican. These
      results suggest that woven bone rich in versican alters into lamellar bone
      containing little versican during bone development in both mandibles and hind
      limbs, where some osteoblasts may be involved in production as well as
      degradation of versican by secreting ADAMTS1, 4, and 5.

PMID- 15983116
TI  - Expression of endothelial NO synthase, inducible NO synthase, and estrogen
      receptors alpha and beta in placental tissue of normal, preeclamptic, and
      intrauterine growth-restricted pregnancies.
AB  - In the physiology of placental blood circulation, nitric oxide (NO) synthases
      seem to play important roles, although their expression in pathological placentas
      and their role is still unclear. In addition, NO synthase activation seems to be
      related to estrogen receptor expression. Therefore, the aims of this study were
      to investigate the expression of estrogen receptors alpha (ERalpha), estrogen
      receptor beta (ER and the endothelial NO synthase (eNOS), and inducible NO
      synthase (iNOS) in intrauterine growth-restricted (IUGR) placentas, preeclamptic
      placentas, and in normal healthy control placentas. Slides of paraffin-embedded
      placental tissue were obtained after delivery from patients diagnosed with IUGR,
      preeclampsia, and normal term placentas and analyzed for eNOS, iNOS as well as
      ERalpha and ERbeta expression. Intensity of immunohistochemical reaction was
      analyzed using a semiquantitative score and statistical analysis was performed.
      In addition, Western blot experiments were performed for comparison of staining
      intensities obtained by immunohistochemistry and western blot. Expression of
      eNOS, iNOS, and ERbeta is significantly reduced in trophoblast cells of placentas
      with IUGR. However, preeclamptic placentas demonstrated a significant elevated
      expression intensity of these proteins compared with normal controls. A different
      expression of eNOS, iNOS, ERalpha, and ERbeta by human trophoblast cells seems to
      results in lower NO output and impaired trophoblast invasion. Results obtained in
      our study provide evidence that reduced expression of the investigated proteins
      is related to IUGR.

PMID- 15983117
TI  - Resin tissue microarrays: a universal format for immunohistochemistry.
AB  - Tissue microarray (TMA) technology allows the miniaturization and
      characterization of multiple tissue samples on a single slide and commonly uses
      formalin-fixed paraffin-embedded (FFPE) tissue or acetone-fixed frozen tissue.
      The former provides good morphology but can compromise antigenicity, whereas the
      latter provides compromised morphology with good antigenicity. Here, we report
      the development of TMAs in glycol methacrylate resin, which combine the
      advantages of both methods in one embedding format. Freshly collected tissue
      fixed in -20C acetone or 10% neutral buffered formaldehyde were cored and arrayed
      into an intermediary medium of 2% agarose before infiltration of the agarose
      array with glycol methacrylate resin. Acetone-fixed resin TMA demonstrated
      improved morphology over acetone-fixed frozen TMA, with no loss of antigenicity.
      Staining for extracellular, cell surface, and nuclear antigens could be realized
      with monoclonal and polyclonal antibodies as well as with monomeric single-chain
      Fv preparations. In addition, when compared with FFPE TMA, formalin-fixed tissue
      in a resin TMA gave enhanced morphology and subcellular detail. Therefore, resin
      provides a universal format for the construction of TMAs, providing improved
      tissue morphology while retaining antigenicity, allows thin-section preparation,
      and could be used to replace preparation of frozen and FFPE TMAs for freshly
      collected tissue.

PMID- 15983119
TI  - Stage-specific expression of dynein light chain-1 and its interacting kinase, p21
      activated kinase-1, in rodent testes: implications in spermiogenesis.
AB  - Mammalian spermatogenesis is a complex process involving regulatory interactions
      of many gene products. In this study, we found that dynein light chain-1 (DLC1),
      a component of the dynein motor complex, is highly expressed in mouse and rat
      testes. Immunohistochemically detectable levels of DLC1 are observed specifically
      in spermatids in steps 9-16 in distinct subcellular compartments: in steps 9-11,
      DLC1 is predominantly localized in the nucleus; in steps 12 and 13, it is found
      in both nucleus and cytoplasm; and in step 14-16, it is present exclusively in
      the cytoplasm. In addition, we found p21-activated kinase 1 (Pak1), a protein
      kinase that activates DLC1 by phosphorylating DLC1 at Serine 88, was also
      expressed during these stages of spermatogenesis. Pak1 was also expressed in
      Leydig cells, in preleptotene primary spermatocytes, and in round spermatids. The
      spermiogenic stage-specific expression of DLC1 suggests a role for DLC1 in
      chromatin condensation, spermatid shaping, and the final release of sperm from
      the spermatogenic epithelium. Further, Pak1 may also play a role in
      spermiogenesis by regulating DLC1 phosphorylation and, consequently, its
      function.

PMID- 15983120
TI  - Analysis of green fluorescent protein expression in transgenic rats for tracking
      transplanted neural stem/progenitor cells.
AB  - Green fluorescent protein (GFP) expression was evaluated in tissues of different
      transgenic rodents--Sprague-Dawley (SD) rat strain [SD-Tg(GFP)Bal], W rat strain
      [Wistar-TgN(CAG-GFP)184ys], and M mouse strain [Tg(GFPU)5Nagy/J]--by direct
      fluorescence of native GFP expression and by immunohistochemistry. The
      constitutively expressing GFP transgenic strains showed tissue-specific
      differences in GFP expression, and GFP immunohistochemistry amplified the
      fluorescent signal. The fluorescence of stem/progenitor cells cultured as
      neurospheres from the ependymal region of the adult spinal cord from the GFP SD
      and W rat strains was assessed in vitro. After transplantation of the cells into
      wild-type spinal cord, the ability to track the grafted cells was evaluated in
      vivo. Cultured stem/progenitor cells from the SD strain required GFP
      immunostaining to be visualized. Likewise, after transplantation of SD cells into
      the spinal cord, immunohistochemical amplification of the GFP signal was required
      for detection. In contrast, GFP expression of stem/progenitor cells generated
      from the W strain was readily detected by direct fluorescence both in vitro and
      in vivo without the need for immunohistochemical amplification. The cultured
      stem/progenitor cells transplanted into the spinal cord survived for at least 49
      days after transplantation, and continued to express GFP, demonstrating stable
      expression of the GFP transgene in vivo.

PMID- 15983118
TI  - Despite transcriptional and functional coordination, cyclooxygenase-2 and
      microsomal prostaglandin E synthase-1 largely reside in distinct lipid
      microdomains in WISH epithelial cells.
AB  - Cytokine-induced prostaglandin (PG)E(2) synthesis requires increased expression
      of cyclooxygenase-2 (COX-2) in human WISH epithelial cells. Recently, an
      inducible downstream PGE synthase (microsomal PGE synthase-1, mPGES-1) has been
      implicated in this inflammatory pathway. We evaluated cooperation between COX-2
      and mPGES-1 as a potential mechanism for induced PGE(2) production in WISH cells.
      Cytokine stimulation led to increased expression of both enzymes. Selective
      pharmacological inhibition of these enzymes demonstrated that induced PGE(2)
      release occurred through a dominant COX-2/mPGES-1 pathway. Unexpectedly,
      immunofluorescent microscopy revealed that the expression of these enzymes was
      not tightly coordinated among cells after cytokine challenge. Within cells
      expressing high levels of both mPGES-1 and COX-2, immunolabeling of high
      resolution semithin cryosections revealed that COX-2 and mPGES-1 were largely
      segregated to distinct regions within continuous intracellular membranes. Using
      biochemical means, it was further revealed that the majority of mPGES-1 resided
      within detergent-insoluble membrane fractions, whereas COX-2 was found only in
      detergent-soluble fractions. We conclude that although mPGES-1 and COX-2 show
      transcriptional and functional coordination in cytokine-induced PGE(2) synthesis,
      complementary morphological and biochemical data suggest that a majority of
      intracellular mPGES-1 and COX-2 are segregated to discrete lipid microdomains in
      WISH epithelial cells.

PMID- 15983121
TI  - Myosin heavy chain isoforms in equine gluteus medius muscle: comparison of mRNA
      and protein expression profiles.
AB  - The major structural protein in skeletal muscle, myosin heavy chain (MyHC), is
      primarily transcriptionally controlled. We compared the expression of MyHC
      isoforms on the mRNA and protein level in biopsies from the m. gluteus medius
      from adult untrained horses. In transverse sections, the majority of fibers
      showed qualitatively identical mRNA and protein expression patterns. However,
      coexpression of 2a and 2d/x MyHCs was substantially more common at the protein
      than at the mRNA level, suggesting a fine-tuning of these two genes in normal
      muscle not subjected to any training protocol. Because transverse sections give a
      limited sampling of mRNA expression in the case of uneven distribution of
      transcripts in a muscle fiber, we also analyzed longitudinal sections. We
      present, for the first time, evidence that expression of MyHC mRNA and protein
      was equal along the length of the fiber. Hence, mRNA expression is not regulated
      by differential expression of isoforms by separate myonuclei. It is concluded
      that the number of protein hybrid fibers in equine gluteus medius muscle is
      controlled by alteration of the transcription pattern uniformly along the fiber,
      rather than by simultaneous transcription of genes. The differences with the
      results in muscle of small animals and humans are discussed.

PMID- 15983122
TI  - Springtime in Illinois.

PMID- 15983123
TI  - A modified capsular shift for atraumatic anterior-inferior shoulder instability.
AB  - PURPOSE: To evaluate the long-term outcome of a modified inferior capsular shift
      procedure in patients with atraumatic anterior-inferior shoulder instability by
      analyzing a consecutive series of patients who had undergone a modified inferior
      capsular shift for this specific type of shoulder instability. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Between 1992 and 1997, 38 shoulders of 35
      patients with atraumatic anterior-inferior shoulder instability that were
      unresponsive to nonoperative management were operated on using a modified
      capsular shift procedure with longitudinal incision of the capsule medially and a
      bony fixation of the inferior flap to the glenoid and labrum in the 1 o'clock to
      3 o'clock position. The patient study group consisted of 9 men and 26 women with
      a mean age of 25.4 years (range, 15-55 years) at the time of surgery. The mean
      follow-up was 7.4 years (range, 4.0-11.4 years); 1 patient was lost to follow-up
      directly after surgery. The study group was evaluated according to the Rowe
      score. RESULTS: After 7.4 years, 2 patients experienced a single redislocation or
      resubluxation, 1 patient had recurrent dislocations, and 1 patient had a positive
      apprehension sign, which is an overall redislocation rate of 10.5%. The average
      Rowe score increased to 90.6 (SD = 19.7) points from 36.2 (SD = 13.5) points
      before surgery. Seventy-two percent of the patients participating in sports
      returned to their preoperative level of competition. CONCLUSIONS: Results in this
      series demonstrate the efficacy and durability of a modified capsular shift
      procedure for the treatment of atraumatic anterior-inferior shoulder instability.

PMID- 15983124
TI  - The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene
      is associated with achilles tendon injuries.
AB  - BACKGROUND: Although there is a high incidence of tendon injury as a result of
      participation in physical activity, the mechanisms responsible for such injuries
      are poorly understood. Investigators have suggested that some people may have a
      genetic predisposition to develop tendon injuries; in particular, genes on the
      tip of the long arm of chromosome 9 might, at least in part, be associated with
      this condition. The tenascin-C gene, which has been mapped to chromosome 9q32
      q34, encodes for a structural component of tendons. HYPOTHESIS: The tenascin-C
      gene is associated with Achilles tendon injury. STUDY DESIGN: Case control study;
      Level of evidence, 3. METHODS: A total of 114 physically active white subjects
      with symptoms of Achilles tendon injury and 127 asymptomatic, physically active
      white control subjects were genotyped for the guanine-thymine dinucleotide repeat
      polymorphism within the tenascin-C gene. RESULTS: A significant difference in the
      allele frequencies of this polymorphism existed between the 2 groups of subjects
      (chi(2) = 51.0, P = .001). The frequencies of the alleles containing 12 repeats
      (symptomatic group, 18.9% vs control group, 10.2%) and 14 repeats (symptomatic
      group, 9.2% vs control group, 0.8%) were significantly higher in the symptomatic
      group, while the frequencies of the alleles containing 13 repeats (symptomatic
      group, 8.8% vs control group, 24.0%) and 17 repeats (symptomatic group, 7.5% vs
      control group, 20.1%) were significantly lower in this same group. Subjects who
      were homozygous or heterozygous for the underrepresented alleles (13 and 17
      repeats) but who did not possess an overrepresented allele (12 and 14 repeats)
      may have a lower risk of developing Achilles tendon injuries (odds ratio, 6.2;
      95% confidence interval, 3.5-11.0; P < .001). CONCLUSIONS: The guanine-thymine
      dinucleotide repeat polymorphism within the tenascin-C gene is associated with
      Achilles tendon injury. Alleles containing 12 and 14 guanine-thymine repeats were
      overrepresented in subjects with tendon injuries, while the alleles containing 13
      and 17 repeats were underrepresented. CLINICAL RELEVANCE: Persons who have
      variants of the tenascin-C gene with 12 and 14 guanine-thymine repeats appear to
      have a 6-fold risk of developing Achilles tendon injuries.

PMID- 15983125
TI  - Effect of fatigue on knee kinetics and kinematics in stop-jump tasks.
AB  - BACKGROUND: Altered motor control strategies in landing and jumping maneuvers are
      a potential mechanism of noncontact anterior cruciate ligament injury. There are
      biomechanical differences between male and female athletes in the landing phase
      of stop-jump tasks. Fatigue is a risk factor in musculoskeletal injuries.
      HYPOTHESIS: Lower extremity muscle fatigue alters the knee kinetics and
      kinematics during the landing phase of 3 stop-jump tasks and increases an
      athlete's risk of anterior cruciate ligament injury. STUDY DESIGN: Controlled
      laboratory study. METHODS: Three-dimensional videography and force plate data
      were collected for 20 recreational athletes (10 male and 10 female athletes)
      performing 3 stop-jump tasks before and after completing a fatigue exercise. Knee
      joint angles and resultant forces and moments were calculated. RESULTS: Both male
      and female subjects had significantly increased peak proximal tibial anterior
      shear forces (P = .01), increased valgus moments (P = .03), and decreased knee
      flexion angles (P = .03) during landings of all 3 stop-jump tasks when fatigued.
      Fatigue did not significantly affect the peak knee extension moment for male or
      female athletes. CONCLUSION: Fatigued recreational athletes demonstrate altered
      motor control strategies, which may increase anterior tibial shear force, strain
      on the anterior cruciate ligament, and risk of injury for both female and male
      subjects. CLINIC RELEVANCE: Fatigued athletes may have an increased risk of
      noncontact anterior cruciate ligament injury.

PMID- 15983126
TI  - Sonographic stress measurement of glenohumeral joint laxity in collegiate
      swimmers and age-matched controls.
AB  - BACKGROUND: Glenohumeral laxity that is greater than normal has been implicated
      as a causal factor in the development of shoulder pain and dysfunction in elite
      swimmers; however, quantitative evidence demonstrating greater-than-normal
      glenohumeral joint laxity in swimmers is lacking. OBJECTIVE: To quantify
      glenohumeral joint laxity in elite swimmers and nonswimming controls using stress
      sonography. STUDY DESIGN: Controlled laboratory study. METHODS: Force
      displacement measures were performed bilaterally in 42 National Collegiate
      Athletic Association Division I swimmers and 44 age-matched controls. Of the 42
      swimmers, 27 (64%) reported a history of unilateral or bilateral shoulder pain
      resulting from swimming. Ultrasound imaging was used to measure glenohumeral
      joint displacement under stressed and non-stressed conditions. RESULTS: An
      analysis of variance revealed no significant difference in glenohumeral joint
      displacement between swimmers (anterior, 2.82 +/- 1.7 mm; posterior, 5.30 +/- 2.4
      mm) and age-matched controls (anterior, 2.74 +/- 1.7 mm; posterior, 4.90 +/- 2.7
      mm). No significant difference in glenohumeral joint displacement was found
      between swimmers with a history of shoulder pain (anterior, 2.90 +/- 1.6 mm;
      posterior, 5.42 +/- 2.3 mm) versus swimmers without a history of shoulder pain
      (anterior, 2.74 +/- 1.8 mm; posterior, 5.14 +/- 2.6 mm). Shoulders displayed
      significantly more glenohumeral joint displacement in the posterior direction
      compared to the anterior direction (P < .001). CONCLUSIONS: Our instrumented
      technique was unable to identify significantly greater glenohumeral joint
      displacement in elite swimmers compared to nonswimming controls, and elite
      swimmers with a history of shoulder pain were not found to have significantly
      more glenohumeral joint displacement compared to swimmers without a history of
      shoulder pain. CLINICAL RELEVANCE: Objective assessment of glenohumeral joint
      displacement in athletes participating in overhead-motion sports may be important
      for injury prevention and management.

PMID- 15983127
TI  - A systematic approach to magnetic resonance imaging interpretation of sports
      medicine injuries of the shoulder.
AB  - Magnetic resonance imaging has developed as a useful imaging modality in the
      evaluation of the athlete with shoulder pain. The multiplanar capabilities of
      magnetic resonance imaging make it ideal for detecting the anatomical variations
      of the osseous outlet that may contribute to the clinical syndrome of
      impingement. Its superb soft tissue contrast and spatial resolution allow for
      accurate differentiation between tendinopathy, partial-thickness tear, and full
      thickness tear of the rotator cuff and also allow for detection of the subtle
      lesions of the capsule and labrum that are associated with shoulder instability.
      However, to accurately interpret the numerous images and pulse sequences obtained
      in a standard magnetic resonance examination of the shoulder, it is helpful to
      have a systematic approach to ensure that each of the pertinent anatomical
      structures are evaluated. This article will provide a systematic approach to the
      interpretation of a magnetic resonance examination of the shoulder. The normal
      imaging appearance of each anatomical structure will be described, and the most
      useful pulse sequences and imaging planes for the evaluation of each structure
      will be discussed. Finally, the signs of injury will be described and
      illustrated.

PMID- 15983128
TI  - Aggressive quadriceps loading can induce noncontact anterior cruciate ligament
      injury.

PMID- 15983129
TI  - Understanding domestic violence resource utilization and survivor solutions among
      immigrant and refugee women: introduction to the special issue.

PMID- 15983130
TI  - "Women must endure according to their karma": Cambodian immigrant women talk
      about domestic violence.
AB  - Asian populations living in the United States share similar cultural values that
      influence their experiences with domestic violence. However, it is critical to
      recognize how differential cultural beliefs in the context of immigration and
      adjustment to life in the United States affect attitudes, interpretations, and
      response to domestic violence. This article discusses findings from community
      based participatory action research that explores how Cambodian immigrant women
      talk about domestic violence, what forms of abuse contribute to domestic
      violence, and what strategies they use to cope with and respond to abuse in their
      lives. The richness of this research lies in the stories that immigrant women
      tell about their struggle and their strength in addressing domestic violence.

PMID- 15983131
TI  - "For us it is like living in the dark": Ethiopian women's experiences with
      domestic violence.
AB  - This article discusses the experiences of domestic violence among Ethiopian
      refugees and immigrants in the United States. A subset (n=18) of the larger study
      sample (N=254) participated in three focus groups with Amharic-speaking survivors
      of domestic violence who were currently in or had left abusive relationships. The
      research was conducted through a public health department, University, and
      community agency partnership. Findings show domestic violence as taking place
      within a context of immigration, acculturation, and rapid changes in family and
      social structure. Participants expressed a need for language and culture-specific
      domestic violence support and advocacy as well as education programs regarding
      U.S. laws and resources.

PMID- 15983132
TI  - "No way out": Russian-speaking women's experiences with domestic violence.
AB  - This article explores the experience of domestic violence and utilization of
      domestic violence resources among immigrant women who were Russian speaking.
      Participants, many of whom came to the United States as so-called mail-order
      brides, reported diverse forms of abuse, including isolation and financial
      restrictions, and were reluctant to get outside help because of embarrassment
      about their circumstances. Survivors stressed the importance of language- and
      culture-appropriate outreach and services and urged that women receive
      information about domestic violence services and laws on immigration. Assistance
      with housing, child care, and job searches is integral to safe transitions out of
      abusive relationships.

PMID- 15983133
TI  - "Like a bird in a cage": Vietnamese women survivors talk about domestic violence.
AB  - In recent years, a growing literature has emerged that explores the role of
      culture in domestic violence for ethnic minority populations, including
      immigrants and refugees. This article presents qualitative data collected from
      Vietnamese refugee women through a research project in partnership with the
      Refugee Women's Alliance in Seattle, Washington. Through the women's stories,
      their own self-awareness of domestic violence as Vietnamese women residing in the
      United States is available for reflection and review. Issues of acculturation,
      changing gender roles, examples of strength, and cultural persistence constitute
      the thematic structure within which these women articulate their needs for
      creating and sustaining a life free of abuse for themselves and their children.

PMID- 15983134
TI  - Participatory action research in practice: a case study in addressing domestic
      violence in nine cultural communities.
AB  - Participatory action research (PAR) is increasingly recognized as a viable
      approach to developing relationships with communities and working closely with
      them to address complex public health problems. In the case of domestic violence
      research, where ensuring the safety of women participants who are battered is
      paramount, participatory approaches to research that include advocates and women
      who are battered in research design, implementation, analysis, and dissemination
      are critical to successful and mutually beneficial projects. This article
      presents a case study of a PAR project that conducted formative qualitative
      research on domestic violence in nine ethnic and sexual minority communities. The
      article describes the specific ways in which a PAR approach was operationalized
      and discusses in detail how community participation shaped various stages of the
      research. Furthermore, specific actions that resulted from the research project
      are reported.

PMID- 15983135
TI  - Binding properties and evolution of homodimers in protein-protein interaction
      networks.
AB  - We demonstrate that protein-protein interaction networks in several eukaryotic
      organisms contain significantly more self-interacting proteins than expected if
      such homodimers randomly appeared in the course of the evolution. We also show
      that on average homodimers have twice as many interaction partners than non-self
      interacting proteins. More specifically, the likelihood of a protein to
      physically interact with itself was found to be proportional to the total number
      of its binding partners. These properties of dimers are in agreement with a
      phenomenological model, in which individual proteins differ from each other by
      the degree of their 'stickiness' or general propensity toward interaction with
      other proteins including oneself. A duplication of self-interacting proteins
      creates a pair of paralogous proteins interacting with each other. We show that
      such pairs occur more frequently than could be explained by pure chance alone.
      Similar to homodimers, proteins involved in heterodimers with their paralogs on
      average have twice as many interacting partners than the rest of the network. The
      likelihood of a pair of paralogous proteins to interact with each other was also
      shown to decrease with their sequence similarity. This points to the conclusion
      that most of interactions between paralogs are inherited from ancestral
      homodimeric proteins, rather than established de novo after duplication. We
      finally discuss possible implications of our empirical observations from
      functional and evolutionary standpoints.

PMID- 15983136
TI  - Ribonuclease PH plays a major role in the exonucleolytic maturation of CCA
      containing tRNA precursors in Bacillus subtilis.
AB  - In contrast to Escherichia coli, where all tRNAs have the CCA motif encoded by
      their genes, two classes of tRNA precursors exist in the Gram-positive bacterium
      Bacillus subtilis. Previous evidence had shown that ribonuclease Z (RNase Z) was
      responsible for the endonucleolytic maturation of the 3' end of those tRNAs
      lacking an encoded CCA motif, accounting for about one-third of its tRNAs. This
      suggested that a second pathway of tRNA maturation must exist for those
      precursors with an encoded CCA motif. In this paper, we examine the potential
      role of the four known exoribonucleases of B.subtilis, PNPase, RNase R, RNase PH
      and YhaM, in this alternative pathway. In the absence of RNase PH, precursors of
      CCA-containing tRNAs accumulate that are a few nucleotides longer than the mature
      tRNA species observed in wild-type strains or in the other single exonuclease
      mutants. Thus, RNase PH plays an important role in removing the last few
      nucleotides of the tRNA precursor in vivo. The presence of three or four
      exonuclease mutations in a single strain results in CCA-containing tRNA
      precursors of increasing size, suggesting that, as in E.coli, the exonucleolytic
      pathway consists of multiple redundant enzymes. Assays of purified RNase PH using
      in vitro-synthesized tRNA precursor substrates suggest that RNase PH is sensitive
      to the presence of a CCA motif. The division of labor between the endonucleolytic
      and exonucleolytic pathways observed in vivo can be explained by the inhibition
      of RNase Z by the CCA motif in CCA-containing tRNA precursors and by the
      inhibition of exonucleases by stable secondary structure in the 3' extensions of
      the majority of CCA-less tRNAs.

PMID- 15983137
TI  - Codon usage comparison of novel genes in clinical isolates of Haemophilus
      influenzae.
AB  - A similarity statistic for codon usage was developed and used to compare novel
      gene sequences found in clinical isolates of Haemophilus influenzae with a
      reference set of 80 prokaryotic, eukaryotic and viral genomes. These analyses
      were performed to obtain an indication as to whether individual genes were
      Haemophilus-like in nature, or if they probably had more recently entered the
      H.influenzae gene pool via horizontal gene transfer from other species. The
      average and SD values were calculated for the similarity statistics from a study
      of the set of all genes in the H.influenzae Rd reference genome that encoded
      proteins of 100 amino acids or longer. Approximately 80% of Rd genes gave a
      statistic indicating that they were most like other Rd genes. Genes displaying
      codon usage statistics >1 SD above this range were either considered part of the
      highly expressed group of H.influenzae genes, or were considered of foreign
      origin. An alternative determinant for identifying genes of foreign origin was
      when the similarity statistics produced a value that was much closer to a non
      H.influenzae reference organism than to any of the Haemophilus species contained
      in the reference set. Approximately 65% of the novel sequences identified in the
      H.influenzae clinical isolates displayed codon usages most similar to Haemophilus
      sp. The remaining novel sequences produced similarity statistics closer to one of
      the other reference genomes thereby suggesting that these sequences may have
      entered the H.influenzae gene pool more recently via horizontal transfer.

PMID- 15983138
TI  - Has preoperative testing become a habit?

PMID- 15983139
TI  - The unanticipated difficult airway--evolving strategies for successful salvage.

PMID- 15983140
TI  - The value of screening preoperative chest x-rays: a systematic review.
AB  - PURPOSE: Chest x-ray (CXR) is the most frequently ordered radiological test in
      Canada. Despite published guidelines, variable policies exist amongst different
      hospitals for ordering of preoperative CXRs. The purpose of this study was to
      systematically review the literature on the value of screening CXRs and establish
      evidence to support guidelines for the use of preoperative screening CXRs.
      SOURCE: Medline and Embase were searched under set terms for all English language
      articles published during 1966-2004. All eligible studies were reviewed and data
      were extracted individually by two authors. Of the 513 articles identified, 14
      studies met both inclusion and exclusion criteria. PRINCIPAL FINDINGS: The
      quality of published evidence was modest as only six of the studies were rated as
      fair and eight as poor. Of the reported studies, diagnostic yield increased with
      age. However, most of the abnormalities consisted of chronic disorders such as
      cardiomegaly and chronic obstructive pulmonary disease (up to 65%). The rate of
      subsequent investigations was highly variable (4-47%). When further
      investigations were performed, the proportion of patients who had a change in
      management was low (10% of investigated patients). Postoperative pulmonary
      complications were also similar between patients who had preoperative CXRs
      (12.8%) and patients who did not (16%). CONCLUSION: An association between
      preoperative screening CXRs and decrease in morbidity or mortality could not be
      established. As the prevalence of CXR abnormalities is low in patients under the
      age of 70, there is fair evidence that routine CXRs should not be performed for
      patients in this age group without risk factors. For patients over 70, there is
      insufficient evidence for or against performance of routine CXRs. The current
      recommendation from the Guidelines Association Committee that routine CXRs should
      not be performed for patients over 70 without risk factors is supported by this
      study.

PMID- 15983141
TI  - Selective ordering of preoperative investigations by anesthesiologists reduces
      the number and cost of tests.
AB  - PURPOSE: Preoperative investigations are frequently ordered according to care
      maps or protocols. We hypothesized that selective ordering of investigations by
      anesthesiology staff would reduce the number and cost of testing. METHODS:
      Prospective descriptive double cohort study carried out over 17 weeks in a
      tertiary care preadmission clinic. In Group 1, testing followed usual practice
      (based on standing preoperative orders) while in Group 2 testing was initiated
      only on the order of an attending anesthesiologist or anesthesiology resident.
      Postoperative complications were categorized and confirmed by an internist
      blinded to group assignment. Fisher's exact test, Chi-square and Student's t test
      were used to compare the groups as appropriate. Statistical significance was
      inferred at P < 0.05. RESULTS: Data were obtained from 507 patients in Group 1
      and 431 patients in Group 2. Demographics and ASA risk score were similar in both
      groups. The mean number of tests ordered did not differ between groups. The mean
      cost of investigations was reduced from 124 dollars in Group 1 to 95 dollars in
      Group 2 (P < 0.05). If data for patients assessed by staff anesthesiologists only
      were considered, the mean cost of testing was reduced to 73 dollars. The number
      and cost of tests ordered by anesthesia residents were similar to that in Group
      1. More complications were noted in Group 2, but these did not appear to be
      related to the altered test ordering practice. CONCLUSION: Selective test
      ordering by staff anesthesiologists reduces the number and cost of preoperative
      investigations. Educational efforts should be directed towards improving resident
      and staff preoperative test ordering practices.

PMID- 15983142
TI  - Transfusion rates vary significantly amongst Canadian medical centres.
AB  - PURPOSE: To document variation of transfusion practice following repair of hip
      fracture or cardiac surgery, as well as those requiring intensive care following
      a surgical intervention or multiple trauma (high risk patients). METHODS: We
      documented rates of allogeneic red cell transfusion in 41,568 patients admitted
      to 11 hospitals across Canada between August 1998 and August 2000 as part of a
      retrospective observational cohort study. In the subgroup of 7,552 patients
      receiving red cells, we also compared mean nadir hemoglobin concentrations from
      centre to centre. RESULTS: The overall rate of red cell transfusion was 38.7%,
      and ranged from 23.8% to 51.9% across centres among the 41,568 perioperative and
      critically ill patients. Women were more likely to be transfused (43.7% vs 35.3%,
      P < 0.0001), with higher rates of transfusion in eight of 11 centres. Compared to
      a chosen reference hospital having a crude transfusion rate near the median, the
      adjusted odds of transfusion ranged from 0.44 to 1.53 overall, from 0.42 to 1.22
      in patients undergoing a hip fracture repair, from 0.72 to 3.17 in cardiac
      surgical patients undergoing cardiac surgery, and from 0.27 to 1.11 in critically
      ill and trauma patients. In the 7,552 transfused patients, the mean adjusted
      nadir hemoglobin was 74.0 +/- 4.83 g x L(-1) overall, and ranged from 66.9 +/-
      1.7 g x L(-1) to 84.5 +/- 1.6 g x L(-1) across centres. Similar differences among
      centres were observed amongst hip fracture patients (71.2 +/- 2.9 g x L(-1) to
      82.8 +/- 1.7 g x L(-1)), cardiac surgical patients (65.7 +/- 1.1 g x L(-1) to
      77.3 +/- 1.0 g x L(-1)) and critically ill and trauma patients (66.1 +/- 3.04 g x
      L(-1) to 87.5 +/- 2.5 g x L(-1)). CONCLUSION: We noted significant differences in
      the rates of red cell transfusion and nadir hemoglobin concentrations in various
      surgical and critical care settings.

PMID- 15983143
TI  - Apnea during induction of anesthesia with sevoflurane is related to its mode of
      administration.
AB  - PURPOSE: The incidence and duration of apnea during sevoflurane anesthesia have
      not been fully characterized. We hypothesized that sevoflurane at slowly
      increasing concentrations reduces incidence and shortens the duration of apnea
      compared to administration of a highly concentrated anesthetic mixture. METHODS:
      131 women were randomly assigned to receive 35% oxygen in air and sevoflurane at:
      incremental concentrations of 1%, from 1% to 8% (group 1-8%, n = 42); decremental
      incremental concentrations of 2%, from 8% to 4% and then from 4% to 8% (group 8-4
      8%, n = 36); or fixed concentrations of 8% for induction of anesthesia (group 8%,
      n = 53). A blinded investigator observed whether and for how long patients
      stopped breathing. RESULTS: All groups reached 2.5 minimum alveolar concentration
      of end-tidal sevoflurane. Although apnea was observed in all groups, it was more
      frequent in the 8% group than in 1 to 8% (68% vs 21%, P < 0.05) or 8 to 4 to 8%
      groups (68% vs 20%, P < 0.05). Duration of apnea was also more pronounced in the
      8% group than in 1 to 8% and 8 to 4 to 8% groups ( 58 +/- 25 s vs 32 +/- 18 sec,
      P < 0.05 and vs 35 +/- 16 sec, P < 0.05, respectively). CONCLUSIONS: Sevoflurane
      induces apnea more frequently and for longer duration at a fixed high
      concentration compared to incremental or decremental-incremental concentrations.
      Decremental-incremental concentrations offer the additional advantage of a speed
      of induction similar to that elicited by the 8% concentration.

PMID- 15983144
TI  - Mechanism of injection pain with long and long-medium chain triglyceride emulsive
      propofol.
AB  - PURPOSE: t has been suggested that long-medium chain triglyceride (LCT/MCT)
      emulsive propofol causes less injection pain than long chain triglyceride (LCT)
      emulsive propofol because of the decreased propofol concentration in the aqueous
      phase. Alternatively, LCT propofol generates bradykinin causing the injection
      pain and activates complement, but these effects when using LCT/MCT propofol have
      not been examined. To identify the mechanism for reduced pain with LCT/MCT
      propofol, injection pain, bradykinin generation and complement activation with
      use of both propofol products were compared. METHODS: Two hundred adult patients
      randomly allocated to two groups were given 1.5 mg x kg(-1) iv of either LCT
      propofol or LCT/MCT propofol at a rate of 200 mg x min(-1) in a double-blind
      manner and were asked to grade pain scores. In another study, bradykinin and
      activated complement 3 (C3a) concentrations were measured using blood obtained
      from 13 healthy volunteers mixed with saline, LCT propofol or LCT/MCT propofol.
      RESULTS: There was a significant difference in pain scores between groups,
      showing a lower incidence of injection pain in the LCT/MCT propofol group. The
      bradykinin concentrations in blood mixed with LCT and LCT/MCT propofol were
      significantly higher than in blood mixed with saline. The C3a concentrations
      showed similar results. CONCLUSIONS: LCT/MCT propofol causes less pain on
      injection compared with LCT propofol. Bradykinin generation and complement
      activation are similar with both LCT and LCT/MCT propofol. Thus, the reason for
      less pain on injection with LCT/MCT propofol may be attributed to a decreased
      concentration of propofol in the aqueous phase.

PMID- 15983145
TI  - The treatment of chronic pain in Quebec: a study of hospital-based services
      offered within anesthesia departments.
AB  - PURPOSE: Little or no information exists on the services that are currently
      available for the treatment of chronic pain across the different regions of
      Canada. As a first step, this study documented the hospital-based resources and
      services offered for the management of chronic non-cancer pain within anesthesia
      departments in Quebec. METHODS: In collaboration with the Association of
      Anesthesiologists of Quebec and the Societe quebecoise de la douleur, a
      provincial survey was conducted to assess the availability of services for
      chronic pain management within hospital-based anesthesia departments along with
      the volume of clinical activities, staff composition, treatments offered and
      space facilities. RESULTS: The response rate was 100%. Fifty of the 69
      departments (73%) offered services for the management of chronic non-cancer pain
      but the services were often limited. Twenty-six percent (13/50) of the
      departments provided some form of multidisciplinary assessment and treatment but
      only three had a core team comprised of an anesthesiologist, a nurse, a
      psychologist, and a physical therapist. Examination of patient waiting lists of
      the surveyed departments revealed disturbing results: approximately 4,500
      patients were waiting for their first appointment to see a pain consultant, and
      nearly 3,000 (67%) had been waiting for nine months or more. CONCLUSION: Although
      this survey did not include the services offered in departments other than
      anesthesia, the results show the extent to which the province of Quebec is under
      resourced for the management of chronic pain patients both in terms of access to
      treatment and quality of the services offered.

PMID- 15983146
TI  - Loss of resistance to normal saline is preferred to identify the epidural space:
      a survey of Canadian pediatric anesthesiologists.
AB  - PURPOSE: Several methods have been described to locate the epidural space, but
      the loss-of-resistance (LOR) technique is the most commonly used. Expert opinion
      states that LOR to air is the best medium for neonates and infants. We conducted
      a Canada-wide postal survey to determine the current state of practice for
      placement of epidural catheters in pediatric patients. METHODS: Two hundred and
      nine surveys were distributed to academic pediatric anesthesiologists across
      Canada. The survey was limited to six questions and was anonymous. RESULTS: The
      response rate was 62.2%. LOR was the method of choice for 124/130
      anesthesiologists (95.4%). LOR to normal saline was the medium of choice for all
      age groups, although LOR to air and LOR to air/saline gained in popularity with
      increasing patient age. The majority of anesthesiologists do not change their LOR
      technique for different patient ages or level of epidural insertion. Most
      responders ranked 'training' as the most important determinant of practice,
      whereas 'departmental guidelines' were considered the least important. No
      complication attributable to the LOR technique used was reported. CONCLUSION: LOR
      to normal saline is the preferred method for identification of the epidural space
      in children of all age groups. The suggestion by experts that LOR to air should
      be used in neonates and infants was not supported by the practice of pediatric
      anesthesiologists across Canada.

PMID- 15983147
TI  - Ketorolac analgesia for inguinal hernia repair is not improved by peripheral
      administration.
AB  - PURPOSE: It has been suggested that ketorolac, a non-steroidal anti-inflammatory
      drug (NSAID) available for parenteral use, may result in prolonged (24 hr)
      postoperative analgesia through a peripheral mechanism when added to local
      anesthetic infiltration. Our objective was to assess this effect by controlling
      for systemic absorption of the drug. METHODS: This randomized, double-blind trial
      studied 40 men undergoing elective inguinal hernia repair under spinal
      anesthesia. All patients received 19 mL of lidocaine 1% infiltrated in the
      operative field before incision. Patients were randomized into two groups of 20.
      The surgical site group received ketorolac 30 mg added to the lidocaine
      infiltration. In the control group, ketorolac 30 mg was injected subcutaneously
      in the contralateral abdominal wall. Numeric rating scores (0-10) of pain at rest
      and with movement were recorded at the time of discharge from the recovery room
      and at 24 hr postoperatively. Time to first analgesia, postoperative iv morphine
      use, total time in the recovery room, and total oral analgesic use in the first
      24 hr were also compared. RESULTS: There were no significant differences between
      groups with respect to any of the measured variables. In both groups, pain scores
      were low at rest (1.9 +/- 1.4 vs 2.2 +/- 1.8, surgical site and systemic groups,
      respectively) and moderate with movement (5.3 +/- 2.2, 5.0 +/- 1.8) after
      anesthetic recovery. Pain scores were similar at 24 hr (1.1 +/- 1.3, 1.9 +/- 1.6
      at rest; 5.7 +/- 2.0, 6.2 +/- 2.2 with movement). CONCLUSION: Adding ketorolac to
      lidocaine infiltration for hernia repair does not improve or prolong
      postoperative analgesia compared to systemic administration.

PMID- 15983148
TI  - Subdural placement of an epidural catheter detected by nerve stimulation.
AB  - PURPOSE: Subdural placement of an epidural catheter is rare and difficult to
      detect. Electrical stimulation of the epidural space can be useful to detect such
      an event. The purpose of the present case report is to confirm the efficacy of
      electrical stimulation to detect a subdural placement of an epidural catheter and
      to illustrate this unusual positioning by computed tomography (CT) scan images.
      CLINICAL FEATURES: A 51-yr-old man was scheduled for an aorto-iliac bypass on a
      combined epidural and general anesthesia technique. Electrical epidural
      stimulation was used. A very low threshold of 0.3 mA was observed with diffuse
      response movement at T3 and at T10, without cerebrospinal fluid return on
      catheter aspiration. An injection of 12 mL of 2% lidocaine with epinephrine
      1/200,000 produced signs of iv injection of local anesthetic and an extensive
      block. Subdural placement of the catheter, suspected by the low current threshold
      response to epidural catheter stimulation, was confirmed by CT scan imaging.
      CONCLUSION: The present case report confirms that electrical stimulation of the
      epidural space is useful to detect misplacement of epidural catheter such as a
      subdural placement. CT scan imaging of subdural positioning of an epidural
      catheter is presented.

PMID- 15983149
TI  - Labour analgesia guided by echocardiography in a parturient with primary dilated
      cardiomyopathy.
AB  - PURPOSE: To evaluate the effects of intrathecal analgesics on cardiac function
      during labour analgesia using echocardiography in a parturient with idiopathic
      dilated cardiomyopathy (DCM). CLINICAL FEATURES: Induction of labour was planned
      in a 35-yr-old primiparous woman suffering from DCM. In order to stabilize
      hemodynamics in this patient, we induced continuous spinal analgesia with an
      infusion of fentanyl and epinephrine. Although her analgesia was well maintained
      for three hours during the first stage of labour, the patient complained of pain
      towards the second stage of labour. At this point, we administered bupivacaine
      intrathecally to alleviate her pain. Transthoracic echocardiography showed that
      the left ventricular end-diastolic and systolic dimensions, as well as the
      ejection fraction were not impaired by use of these analgesic medications.
      CONCLUSION: Measurement of left ventricular dimensions by echocardiography
      allowed us to monitor the patient's response to intrathecal analgesic
      medications. In this patient with DCM, analgesia with intrathecal fentanyl and
      bupivacaine was well tolerated.

PMID- 15983150
TI  - Brief report: The declining incidence of cerebral hyperthermia during cardiac
      surgery: a seven-year experience in 6,334 patients.
AB  - PURPOSE: Cerebral hyperthermia during rewarming from hypothermic cardiopulmonary
      bypass (CPB) commonly occurs and has been associated with postoperative
      neurocognitive dysfunction. Increased awareness of this has likely led to changes
      in rewarming strategies, including the reduction of rewarming rates and lowering
      of target rewarming temperatures. As a result, we hypothesized that the maximum
      temperature reached during cardiac surgery has decreased at our institution over
      time. METHODS: We retrospectively reviewed the maximum intraoperative
      nasopharyngeal (NP) temperature in 6,334 patients having undergone cardiac
      surgery utilizing hypothermic CPB from January 1993 to June 2000. The incidence
      of cerebral hyperthermia (defined by a NP temperature > 38 degrees C) was
      examined over time using Chi-square testing and the relationship between maximum
      temperature and date of surgery was studied using linear regression. RESULTS:
      Maximum temperature decreased over time (P < 0.0001; r2 = 0.40) having the
      greatest reduction from January 1993 to December 1996 (0.34 degrees C temperature
      drop per year), while from January 1997 to June 2000, it continued to decrease,
      but at a slower rate (0.10 degrees C per yr; P < 0.0001). The incidence of
      cerebral hyperthermia decreased over time with 83% of the first 10% of patients
      and 3% of the latter 10% of patients during the study period having a maximum
      temperature > 38 degrees C (P < 0.0001). CONCLUSION: The incidence of cerebral
      hyperthermia has decreased at our institution suggesting that a change in
      temperature management has occurred at our institution from January 1993 to June
      2000 thereby outlining a temporal evolution in temperature management during CPB.

PMID- 15983151
TI  - The Proseal LMA is a useful rescue device during failed rapid sequence
      intubation: two additional cases.
AB  - PURPOSE: We report two cases where the ProSeal laryngeal mask airway (PLMA) was
      successfully used as a rescue device, after failed tracheal intubation, during
      rapid sequence induction. CLINICAL FINDINGS: The first case involved a 31-yr-old
      primigravida presenting for emergency Cesarean section for severe fetal distress.
      She had a grade 3 larynx and airway edema was observed during laryngoscopy.
      Attempts with a McCoy blade and gum elastic bougie failed to secure the airway. A
      size 4 PLMA was inserted with good airway control and surgery proceeded
      uneventfully. The second case involved a 51-yr-old man presenting for
      appendectomy. Following failed attempts at intubation, a size 5 PLMA was
      successful in securing his airway and surgery proceeded uneventfully.
      CONCLUSIONS: The correctly placed PLMA has potential advantages over the cLMA for
      airway rescue in the circumstance of failed emergency intubation in a patient
      with a potentially full stomach. In the two cases reported, the PLMA provided
      effective rescue of the airway.

PMID- 15983152
TI  - Airway management after failure to intubate by direct laryngoscopy: outcomes in a
      large teaching hospital.
AB  - PURPOSE: The purpose of this single-centre database review was to establish the
      incidence of failure to intubate by direct laryngoscopy, to measure morbidity and
      mortality associated with this event, and to examine the use and efficacy of
      alternative airway devices. METHODS: Difficult intubation via direct laryngoscopy
      at Mayo Clinic Rochester is recorded in an electronic database using a functional
      classification: 0 = no difficulty; 1 = mild to moderate difficulty; and 2 =
      severe difficulty often requiring a change in intubation technique. Using this
      database, the total number of intubations was determined for a selected review
      period and the incidence of failure to intubate by direct laryngoscopy was
      established. Abstraction of chart data allowed for determination of associated
      morbidity and mortality, success of alternative airway devices, and case
      cancellation rate. RESULTS: During the period from August 1, 2001 through
      December 31, 2002, 37,482 patients underwent general anesthesia with attempted
      direct laryngoscopy. One hundred sixty-one patients (0.43%) could not be
      intubated by direct laryngoscopy alone. Morbidity associated with difficult
      intubation included soft tissue/dental damage (n = 8), intraoperative cardiac
      arrest (n = 1), and possible aspiration (n = 1). Three patients required
      intensive care unit admission. There was no associated mortality. The most
      commonly used alternative airway device was the flexible fibreoptic scope. Five
      case cancellations resulted from failure to intubate with alternative devices.
      CONCLUSION: The rate of unexpected failure to intubate by direct laryngoscopy is
      essentially unchanged from earlier studies. While morbidity was low, continued
      education and early use of alternative difficult airway devices may further limit
      complications associated with this event.

PMID- 15983153
TI  - The LMA Fastrach facilitates fibreoptic intubation in oral cancer patients.
AB  - PURPOSE: To compare ease of endotracheal intubation with the Intubating Laryngeal
      Mask Airway (ILMA) tracheal tube (TT; for LMA-Fastrach) and regular PVC TT
      (Portex) for nasotracheal fibreoptic intubation in oral cancer patients with a
      difficult airway. METHODS: 40 patients of physical status ASA I-II with a history
      of previous oral cancer surgery and/or postoperative radiotherapy scheduled for
      oral cancer surgery were randomly allocated by sealed envelopes to undergo
      tracheal intubation with either the ILMA TT or a standard TT. Ease of nasal
      passage of the TT and ease of tracheal intubation over the fibrescope was
      assessed. Peak airway pressures were assessed intraoperatively and
      postoperatively for 12 hr. RESULTS: The use of the ILMA TT increased the ease of
      nasotracheal intubation by increasing the percentage of successful tube
      placements at the first attempt (80%) in comparison with standard TT (35%); (P <
      0.05). Peak airway pressures were found to remain low with the ILMA TT. None of
      the patients experienced any airway related complications. CONCLUSIONS: Use of a
      soft, flexible, nonkinking ILMA TT with a tapered tip design facilitates passage
      into the trachea over a fibreoptic bronchoscope and allows maintenance of lower
      airway pressures. The ILMA TT may be a useful adjunct for management of the
      difficult airway in oral cancer surgery.

PMID- 15983154
TI  - Use of the Aintree intubation catheter in a patient with an unexpected difficult
      airway.
AB  - PURPOSE: To present a case where the Aintree intubation catheter (AIC) was used
      in conjunction with the Laryngeal Mask Airway (LMA) and a fibreoptic bronchoscope
      (FOB) in a patient with an unexpected difficult airway. CLINICAL FEATURES: A 38
      yr-old 90 kg man scheduled for nasal endoscopy with ethmoidectomy under general
      anesthesia was found, unexpectedly, to be difficult to intubate using both a
      Macintosh laryngoscope (#4 blade) and a GlideScope video laryngoscope despite
      having an airway examination that was unremarkable except for slightly decreased
      mouth opening and a large tongue. Intubation was achieved by inserting a size 5
      disposable LMA into the upper airway, introducing a FOB into an AIC inserting the
      FOB/AIC assembly into the trachea via the LMA, removing the LMA, and then passing
      a regular size (7.5 mm) endotracheal tube into the trachea over the AIC.
      CONCLUSION: In this patient, the AIC provided an effective alternative to other
      methods for intubating through a regular LMA.

PMID- 15983155
TI  - Best evidence in critical care medicine: Stress ulcer prophylaxis in the
      intensive care unit: damned if you do, damned if you don't.

PMID- 15983156
TI  - Another method to assist nasogastric tube insertion.

PMID- 15983157
TI  - Epidural combined with propofol anesthesia does not suppress the hyperglycemic
      response to abdominal surgery.

PMID- 15983158
TI  - Re-expansion pulmonary edema following laparotomy for volvulus.

PMID- 15983159
TI  - Pre-existing otitis media and hearing impairment after interscalene block
      combined with general anesthesia.

PMID- 15983160
TI  - Thyroid cyst puncture during cannulation of the internal jugular vein.

PMID- 15983161
TI  - Antecubital approach for monitoring jugular bulb venous oxygen saturation during
      carotid endarterectomy.

PMID- 15983162
TI  - Use of Shikani Flexible Seeing Stylet for intubation via the Intubating Laryngeal
      Mask Airway.

PMID- 15983163
TI  - Using a Glidescope for intubation with a double lumen endotracheal tube.

PMID- 15983164
TI  - Optimum contents of a portable emergency airway equipment bag: results of an
      institutional survey.

PMID- 15983165
TI  - Medium-/long-chain triglyceride emulsion reduced severity of pain during propofol
      injection.

PMID- 15983166
TI  - Considerations aimed at facilitating the use of the new GlideScope
      videolaryngoscope.

PMID- 15983167
TI  - On the possible use of annual killifishes as models for aging research: a comment
      on Herrera and Jagadeeswaran.

PMID- 15983168
TI  - Genes, phenes, and dreams of immortality: the 2003 Kleemeier Award lecture.
AB  - The 2002 Kleemeier Award from the Gerontological Society of America was awarded
      to Thomas E. Johnson, PhD, of the University of Colorado at Boulder. Dr. Johnson
      was the pioneer who first applied genetic analyses to the study of the aging
      processes in Caenorhabditis elegans and who introduced the nematode as an aging
      model. Longer life span was chosen as a surrogate marker for slowed aging. Here
      Dr. Johnson describes his role(s) in the isolation of age-1, the first longevity
      mutant, which can more than double the life span and which slows the rate of
      aging more than twofold. He also reviews research suggesting conservation of
      function and applicability to intervention by pharmacological targeting of the
      Age-1 pathway. Current work by biotechnology companies targets this and other
      basic discoveries in an attempt to postpone human aging.

PMID- 15983169
TI  - Caloric restriction decreases survival of aged mice in response to primary
      influenza infection.
AB  - Caloric restriction (CR) extends life span of healthy rodents compared to those
      fed ad libitum. Previous studies have shown positive effects of CR on the immune
      response of aged mice after influenza immunization. To extend these studies, a
      mouse model of CR was used to determine if CR could modulate primary responses of
      aged mice to influenza. Although CR delayed the age-related decrease in mitogen
      induced lymphoproliferation of aged mice, in stark contrast, CR decreased
      survival, increased virus titers, and reduced natural killer cell activity in
      lungs of aged mice after primary influenza infection. Thus, CR has differential
      effects on immunity of aged mice, as general indices of immune response are
      maintained, but primary responses to influenza infection are impaired. This
      suggests that, although CR may positively affect many long-term parameters of
      aging, increased susceptibility after primary exposure of aged mice to virus,
      such as influenza, may not be correctable by CR.

PMID- 15983170
TI  - The comet assay approach to senescent human diploid fibroblasts identifies
      different phenotypes and clarifies relationships among nuclear size, DNA content,
      and DNA damage.
AB  - The comet assay methodology was used to monitor nuclear changes occurring in MRC5
      human fibroblasts during transition from young to senescent cultures and to study
      heterogeneity of senescent populations. Nuclear morphology and size, DNA content
      per nucleus, and DNA damage (basal strand break, total damage, and oxidized base
      levels) were evaluated; moreover, visually identified large and small nuclei were
      analyzed separately and arranged in classes of increasing DNA damage. Oxidized
      base levels were definitely lower in young versus senescent fibroblasts of which,
      however, a significant proportion showed negligible DNA damage. Nuclear size
      enlargement accompanying senescence was almost equally influenced by cell ploidy
      increase and also by a chromatin decondensation process involving diploid cells.
      It is noteworthy that DNA damage in senescent fibroblasts correlated
      significantly to nuclear size, but not to DNA content. The comet assay allowed us
      to identify different senescent phenotypes and to investigate changes in nuclear
      features and/or DNA damage irrespective of time elapsed in culture.

PMID- 15983171
TI  - Involvement of nitric oxide-mediated intrinsic pathway signaling in age-related
      increase in germ cell apoptosis in male Brown-Norway rats.
AB  - We examined, using young and old Brown-Norway rats, the involvement of the nitric
      oxide (NO)-mediated intrinsic pathway signaling in age-related activation of male
      germ-cell apoptosis. Increased apoptosis of germ cells was readily observed in
      the normal-looking testes of old rats. Testicular NO synthase (NOS) activity,
      assessed by measuring the synthesis of (3)H-L-citrulline from (3)H-L-arginine,
      and cytokine-inducible NO synthase (iNOS) levels, assessed by western blot assay,
      were increased significantly by 90% and 70%, respectively, in the old rats
      compared to that of young animals. Immunohistochemical analysis of age-related
      changes in the expression of iNOS in testes confirmed our findings based on
      western blot assay. Increased NO and germ-cell apoptosis during aging is further
      associated with cytosolic translocation of mitochondrial cytochrome c and poly
      (ADP) ribose polymerase (PARP) cleavage, thus, suggesting the involvement of NO
      mediated intrinsic pathway signaling in age-related increase in germ-cell
      apoptosis in male Brown-Norway rats.

PMID- 15983172
TI  - Effects of human Na(+)/dicarboxylate cotransporter 3 on the replicative
      senescence of human embryonic lung diploid fibroblasts.
AB  - To investigate the role of human Na(+)/dicarboxylate cotransporter 3 (hNaDC3) in
      the replicative senescence of normal human embryonic lung diploid fibroblasts (WI
      38), a retroviral vector containing hNaDC3 was constructed. hNaDC3 was introduced
      into normal WI-38 cells through infection with the retroviral virus. Monoclones
      were selected with G418. The integration and expression of exotic genes were
      confirmed by Northern blot and Western blot. When compared with the control
      cells, WI-38 cells transfected with hNaDC3 cDNA showed significant suppression of
      growth rate (by 40%), increase of positive rate of SA-beta-gal staining, decrease
      of mitochondrial membrane potential, shortening of telomere length, and increase
      of P16 and P21 expression. The morphology characteristics of senescent
      fibroblasts appeared earlier. Our results have, for the first time, demonstrated
      that high expression of hNaDC3 may be able to, at least partly, promote the
      cellular senescence of human diploid fibroblasts.

PMID- 15983173
TI  - Age-related changes of mitochondrial DNA content and mitochondrial genotypic and
      phenotypic alterations in rat hind-limb skeletal muscles.
AB  - Mitochondrial DNA (mtDNA) content relative to nuclear DNA content as well as
      mitochondrial transcription factor A (TFAM) content was measured in four hind
      limb skeletal muscles, namely soleus (S), tibialis anterior (TA), gastrocnemius
      (G), and extensor digitorum longus (EDL) of adult rats. Content of mtDNA in 6
      month-old rats is in the rank order of S > TA > G > EDL, and TFAM content is
      higher in S than in the other studied muscles. After the rat is 6 months of age,
      the mtDNA content decreases only in S and TA, whereas the TFAM content increases
      only in S. Deletions in mtDNA appear quite early in life in S and later on in the
      other muscles. Fibers defective for mitochondrial respiratory enzymes appear in
      rats at 15 months of age. In the oldest animals, the highest frequencies of
      occurrence of mtDNA deletions as well as of mitochondrial phenotypic alterations
      are found in S according to its highest mtDNA content and oxidative potential.

PMID- 15983174
TI  - Closing in on a killer: anemia in elderly people.

PMID- 15983175
TI  - Impact of anemia and cardiovascular disease on frailty status of community
      dwelling older women: the Women's Health and Aging Studies I and II.
AB  - BACKGROUND: The physiological basis of the geriatric syndrome of frailty, a
      clinical state of increased vulnerability to adverse outcomes such as disability
      and mortality, remains to be better characterized. We examined the cross
      sectional relationship between hemoglobin (Hb) and a recently-validated measure
      of frailty in community-dwelling older women, and whether this relationship was
      modified by cardiovascular disease (CVD) status. METHODS: Data were pooled from
      women 70-80 years old participating in the Women's Health and Aging Studies I and
      II (Baltimore, MD, 1992-1996) with known frailty status and Hb > or = 10 g/dL (n
      = 670). Logistic regression was used to model the relationship between frailty
      and Hb, adjusting for demographics, major chronic diseases, and physiologic and
      functional impairments. RESULTS: Prevalence of frailty was 14%. Frailty risk was
      highest at the lowest Hb levels, and lowest at mid-normal Hb levels (e.g., 13-14
      g/dL). Mildly low and low-normal Hb concentrations were independently associated
      with frailty. Compared to an Hb concentration equal to 13.5 g/dL, the adjusted
      odds of being frail were 1.9 (95% confidence interval: 1.1-3.4) and 1.5 (95%
      confidence interval: 1.0-2.1) times higher for Hb concentrations equal to 11.5
      g/dL and 12 g/dL, respectively. A statistically significant (p <.05)
      multiplicative interaction between Hb level and CVD status with respect to
      frailty risk was observed. CONCLUSION: In community-dwelling older women, mildly
      low and low-normal Hb levels were independently associated with increased frailty
      risk. This risk was synergistically modified by the presence of CVD. These
      results suggest that mild anemia, and even low-normal Hb levels are independent,
      potentially modifiable risk factors for frailty in community-dwelling older
      adults.

PMID- 15983176
TI  - Sex, hormones, and Alzheimer's disease.
AB  - More women than men have Alzheimer's disease (AD). Retrospective studies
      suggested that hormone replacement therapy (HRT) might counteract this disparity
      by reducing the risk of developing dementia. However, a recent, large,
      prospective study revealed the puzzling result that HRT increased dementia risk.
      A review of the literature was conducted to generate hypotheses that might
      explain why more women than men have AD, and how HRT may increase dementia risk.
      Longer life span of women than men may be the largest factor in the preponderance
      of women with AD. Longer duration of disease, less vascular dementia, and less
      testosterone in women than men may also contribute somewhat. HRT might increase
      dementia risk by several mechanisms: greater risk of strokes, leading to
      dementia; use of medroxyprogesterone acetate and estrone, which might have
      somewhat different possible effects on neuronal and cerebrovascular function than
      may progesterone and estradiol; decrease of free testosterone which might protect
      against AD; a dose or delivery method perhaps producing drug levels that might
      lie outside a hypothetical beneficial range; and down-regulation of estrogen
      receptors on cholinergic neurons, possibly reducing cholinergic activity. Further
      study is required to discern by which of several possible mechanisms HRT
      increases dementia risk.

PMID- 15983177
TI  - Do depressive symptoms predict Alzheimer's disease and dementia?
AB  - BACKGROUND: Depressive symptoms are common in seniors and may predict dementia.
      The objective of this study was to evaluate multiple measures of depressive
      symptoms to determine whether they predict subsequent Alzheimer's disease (AD) or
      dementia. METHODS: This population-based cohort study with 5-year follow-up
      included 766 community-dwelling seniors (ages 65+ years) in Manitoba, Canada.
      Measurements considered were the Center for Epidemiologic Studies Depression (CES
      D) scale, participant-reported medical history, and duration of depression.
      RESULTS: Total CES-D score was a significant predictor of AD and dementia when
      categorized as a dichotomous variable according to the cutoff scores of 16 and
      17; a CES-D cutoff of 21 was a significant predictor of AD and a marginally
      significant predictor of dementia. When analyzed as a continuous variable, CES-D
      score was marginally predictive of AD and dementia. Neither participant-reported
      history of depression nor participant-reported duration of depression was
      significant in predicting AD or dementia. CONCLUSION: Because depressive symptoms
      as measured by the CES-D predict the development of AD and dementia over 5 years,
      clinicians should monitor their older patients with these symptoms for signs of
      cognitive impairment.

PMID- 15983178
TI  - Delirium superimposed on dementia in a community-dwelling managed care
      population: a 3-year retrospective study of occurrence, costs, and utilization.
AB  - BACKGROUND: Dementia is a growing public health problem and a well-described risk
      factor for delirium. Yet little is known about delirium superimposed on dementia
      in community-dwelling populations. The purpose of this study was to examine the 3
      year occurrence, healthcare utilization, and costs associated with delirium
      superimposed on dementia in community-dwelling persons. METHODS: We used a 3-year
      cross-sectional, retrospective design with an administrative database from a
      large managed care organization. Four individually matched samples of 699
      individuals each were selected for comparison purposes: delirium superimposed on
      dementia (DSD), dementia alone, delirium alone, and a control group with neither
      delirium nor dementia. The occurrence rate of DSD was calculated by measuring
      those individuals with a dementia diagnosis that were also coded with an
      International Classification of Diseases, Ninth Edition Clinical Modification
      (ICD-9 CM) code for delirium or delirium with dementia. RESULTS: Of the total
      sample of 76,688 persons aged 65 years or older in the managed care organization,
      7347 (10%) were coded as having dementia, and an additional 763 (1%) as having
      delirium alone. Among the 7347 with dementia, 976 (13%) had DSD, representing
      1.3% of the total sample. After log transformation of total costs and adjustment
      for multiple covariates, the adjusted mean total health care costs remained
      significantly higher for the DSD group than for all other groups. CONCLUSIONS:
      This study is the first to report the occurrence rate of DSD in a community
      dwelling population, and to demonstrate the substantial health care costs and
      utilization associated with DSD.

PMID- 15983179
TI  - Vitamin D supplementation in older women.
AB  - BACKGROUND: The purpose of this study was to determine if vitamin D
      supplementation, 400-800 IU daily, could effectively treat vitamin D deficiency
      and insufficiency over 3 months. METHODS: To test this hypothesis, we conducted a
      cross-sectional survey followed by a 3-month, open-label run-in phase prior to a
      randomized clinical trial. We enrolled 573 community-dwelling women age 65 or
      older, 373 of whom completed the run-in phase. All women received a daily
      multivitamin containing 400 IU of vitamin D and one to two calcium supplements
      containing 200 IU of vitamin D. We assessed bone mineral metabolism (including 25
      hydroxyvitamin D and parathyroid hormone), markers of bone turnover, and bone
      mineral density. RESULTS: Of the 553 screened participants who had baseline
      vitamin D levels available, 16% had vitamin D deficiency (serum vitamin D < 10
      ng/ml) and 48% had vitamin D insufficiency (serum vitamin D between 10 and 20
      ng/ml). Only 36% of participants had normal vitamin D levels (serum vitamin D >
      or = 20 ng/ml). Baseline vitamin D intake was negatively associated with serum
      parathyroid hormone (r = -0.29, p <.0001), and not associated with bone mineral
      density or bone resorption. Vitamin D deficiency was associated with decreased
      physical activity and slower gait. Of the 373 women who completed the run-in
      phase and received treatment with a multivitamin and vitamin D-containing calcium
      supplement, vitamin D deficiency decreased from 16% at baseline to 0% at 3
      months, and vitamin D insufficiency decreased from 48% at baseline to 20% at 3
      months (p <.001). CONCLUSIONS: We conclude that vitamin D deficiency and
      insufficiency, which are common among ambulatory, community-dwelling elderly
      women, can be normalized in 80% of patients over 3 months with vitamin D
      supplementation of 400-800 IU/d.

PMID- 15983180
TI  - Association between physical activity, physical performance, and inflammatory
      biomarkers in an elderly population: the InCHIANTI study.
AB  - BACKGROUND: Our aim was to determine the association between physical activity
      and physical performance, and inflammatory biomarkers in elderly persons.
      METHODS: One thousand four persons aged 65 years or more, participants in a cross
      sectional population-based study, were included. Interviewers collected
      information on self-reported physical activity during the previous year.
      Moreover, 841 participants performed a 400-meter walking test to assess physical
      performance. Plasma concentrations of inflammatory biomarkers were determined.
      RESULTS: Compared to sedentary men, men practicing light and moderate-high
      physical activity had a significantly lower erythrocyte sedimentation rate (-0.33
      and -0.40 mm/h; p =.023 and p =.006, respectively), fibrinogen level (-43 and -39
      mg/dL; p =.001 and p =.004, respectively), and logarithm of C-reactive protein
      (CRP) (-0.43 and -0.73 mg/L; p =.025 and p <.001, respectively), whereas only
      those men practicing moderate-high physical activity had a significantly lower
      uric acid level (-0.57 mg/dL; p =.023), log(interleukin 6) levels (-0.33 pg/mL; p
      =.014), and log(tumor necrosis factor-alpha) (-0.31 pg/mL; p =.030). In women,
      those practicing light and moderate-high physical activity had significantly
      lower uric acid (-0.45 and -0.34 mg/dL; p =.001 and p =.039, respectively) and
      log(interleukin 6) levels (-0.18 and -0.30 pg/mL; p =.043 and p =.004,
      respectively); only those women practicing moderate-high physical activity had
      significantly lower log(CRP) (-0.31 mg/L; p =.020). In women, when the analysis
      was adjusted for body mass index, the association between physical activity and
      CRP was no longer significant. Similar findings were observed when we carried
      these analyses according to physical performance. CONCLUSIONS: Current physical
      activity practice and performance are associated with inflammatory biomarkers. A
      significant beneficial association is already observed with light physical
      activity practice and intermediate performance.

PMID- 15983181
TI  - A randomized controlled trial of high versus low intensity weight training versus
      general practitioner care for clinical depression in older adults.
AB  - BACKGROUND: Although exercise has been shown to relieve depression, little is
      known about its mechanism or dose-response characteristics. We hypothesized that
      high intensity progressive resistance training (PRT) would be more effective than
      either low intensity PRT or standard care by a general practitioner (GP) in
      depressed elderly persons, and that high intensity PRT would provide superior
      benefits in quality of life, sleep quality, and self-efficacy. METHODS: Sixty
      community-dwelling adults >60 years with major or minor depression were
      randomized to supervised high intensity PRT (80% maximum load) or low intensity
      PRT (20% maximum load) 3 days per week for 8 weeks, or GP care. RESULTS: A 50%
      reduction in the Hamilton Rating Scale of Depression score was achieved in 61% of
      the high intensity, 29% of the low intensity, and 21% of the GP care group (p
      =.03). Strength gain was directly associated with reduction in depressive
      symptoms (r = 0.40, p =.004), as was baseline social support network type (F =
      3.52, p =.015), whereas personality type, self-efficacy, and locus of control
      were unrelated to the antidepressant effect. Vitality quality-of-life scale
      improved more in the high intensity group than in the others (p =.04). Sleep
      quality improved significantly in all participants (p <.0001), with the greatest
      relative change in high intensity PRT (p =.05). CONCLUSIONS: High intensity PRT
      is more effective than is low intensity PRT or GP care for the treatment of older
      depressed patients.

PMID- 15983182
TI  - Effects of maximal isometric and isokinetic resistance training on strength and
      functional mobility in older adults.
AB  - BACKGROUND: The aim of the present study was to compare the changes in voluntary
      strength (isometric, concentric, and eccentric) and functional mobility in
      response to maximal isokinetic eccentric-only resistance training to those
      elicited by maximal isometric-only or maximal isokinetic concentric-only
      resistance training in older adults. METHODS: Twelve women (73 +/- 7 years) and
      18 men (73 +/- 5 years) completed a 12-week training program (three times per
      week) using a Biodex System 3 dynamometer. Primary outcome measures included peak
      isometric and isokinetic (concentric and eccentric) knee extensor strength,
      concentric work, concentric power, stair ascent and descent, and gait speed.
      Participants were randomly assigned to one of three training groups: isometric
      only, isokinetic concentric-only, or isokinetic eccentric-only. RESULTS: All
      three training groups demonstrated an increase in peak isometric and isokinetic
      concentric and eccentric strength following 12 weeks of training (p <.01). Step
      time was positively influenced (p <.03) by all three training modes; however,
      gait speed was unchanged following 12 weeks of training. All three training
      groups experienced a significant increase in peak concentric work and concentric
      power (p <.01) with the concentric training group demonstrating the largest
      increases in both peak concentric work and concentric power when compared to the
      isometric and eccentric training groups. CONCLUSIONS: It was clear that all three
      resistance training programs (isometric, concentric, and eccentric) in older
      adults were effective in increasing strength, concentric work, and concentric
      power over the 12-week training period. Furthermore, 12 weeks of resistance
      training resulted in improved stair ascent and descent performance.

PMID- 15983183
TI  - Effects of age and fitness on tolerance to lower body negative pressure.
AB  - BACKGROUND: The purpose of this investigation was to determine the effects of age
      and fitness on tolerance to maximal lower body negative pressure (LBNP). METHODS:
      Ten older fit (OF) [73.9 +/- 2 years; 39.0 +/- 2 ml.kg(-1).min(-1) (age and
      estimated VO(2)peak, respectively)], 10 older unfit (OU) (70.9 +/- 1 years; 27.1
      +/- 2 ml.kg(-1).min(-1)), 10 young fit (YF) (22.6 +/- 0.5 years; 57.1 +/- 2
      ml.kg(-1).min(-1)), and 10 young unfit (YU) (23.1 +/- 1 years; 41.1 +/- 2 ml.kg(
      1).min(-1)) participants underwent graded LBNP of -10 mmHg every 4 minutes to
      either presyncope or -100 mmHg. RESULTS: Compared to the other groups, YF had an
      earlier increase in heart rate (-40 mmHg vs the last stage; YF vs OF, OU, and YU,
      respectively) and decline in stroke volume (-20 mmHg vs -40 mmHg; YF vs OF, OU,
      and YU, respectively). OU had a higher resting mean arterial pressure; this
      difference was maintained until the last stage. OF had an earlier decline in
      total peripheral conductance than the other groups (-20 mmHg vs -40 mmHg).
      Tolerance to maximal LBNP did not differ among the groups. CONCLUSIONS: Despite
      differences in the responses to submaximal LBNP, neither age nor cardiovascular
      fitness affect tolerance to maximal LBNP.

PMID- 15983184
TI  - Outcomes of continuous process improvement of nutritional care program among
      geriatric units.
AB  - BACKGROUND: Up to 65% of elderly patients are protein-calorie undernourished at
      admission or acquire nutritional deficits while hospitalized. The aims of this
      project were: (a) to assess the quality of care concerning nutrition among
      Belgian geriatric units, (b) to include more routinely nutritional assessments
      and interventions in comprehensive geriatric assessment, and (c) to assess the
      impact of nutritional recommendations on nutritional status and on the length of
      hospitalization. Method. We studied 1139 patients consecutively admitted to 12
      geriatric units of general hospitals prospectively for 6 months (from January
      through June 2001). All patients underwent a comprehensive geriatric assessment.
      For the first 3 months, the nutritional status of the patients on admission and
      at discharge were assessed without particular recommendations for nutritional
      intervention. A standardized nutritional intervention was proposed for the last 3
      months. RESULTS: Median value of the Mini Nutritional Assessment test score was
      18 points (range 9-29), mean admission's serum prealbumin concentration was 0.185
      +/- 0.076 g/L, and C-reactive protein was 5.3 +/- 7.5 mg/100 ml. Hospitalization
      stay was significantly lower during the interventional period than during the
      observational period. A higher mean serum prealbumin concentration variation was
      observed during the interventional period as compared to the observational
      period. CONCLUSIONS: Nutritional assessment should be part of routine clinical
      practice in elderly hospitalized patients. A comprehensive screening tool for
      assessment of nutritional status is needed that is clinically relevant and cost
      effective to perform. If malnutrition is suggested by such screening tests, then
      a supplemental conventional nutritional assessment should be performed before
      treatment is planned.

PMID- 15983185
TI  - Back pain and decline in lower extremity physical function among community
      dwelling older persons.
AB  - BACKGROUND: Little is known regarding the longitudinal effects of back pain on
      physical function among older persons. We sought to determine whether back pain
      leading to activity restriction (i.e., restricting back pain) is associated with
      decline in lower extremity physical function among community-dwelling older
      persons. METHODS: In this prospective study with an 18-month follow-up period,
      participants (N = 659) were aged 70 years or older and independent in bathing,
      dressing, transferring, and walking at baseline. Restricting back pain, defined
      as staying in bed for at least one-half day or cutting down on one's usual
      activities due to back pain, was ascertained during monthly telephone interviews.
      Lower extremity physical function was assessed using three timed, performance
      based tests (rapid gait, chair stands, and foot taps) at baseline and 18 months.
      Decline in lower extremity physical function was defined as an increase in timed
      scores on these tests between the baseline and 18-month assessments. RESULTS: The
      mean (standard deviation) number of months with restricting back pain was 1.3
      (2.3); 364 (55%) participants reported 0 months, 209 (32%) reported 1-3 months,
      and 86 (13%) reported 4 or more months. After adjustment for baseline performance
      score and other covariates, the number of months with restricting back pain was
      independently associated with worsening rapid gait (p <.001), chair stand (p
      =.030), and foot tap (p <.001) performance. The deleterious effects of the
      "exposure" were limited to participants with 4 months of restricting back pain.
      CONCLUSIONS: Restricting back pain is independently associated with decline in
      lower extremity physical function among community-dwelling older persons.
      Treatment of restricting back pain may help to decrease functional decline in
      this population.

PMID- 15983186
TI  - Geriatric evaluation and management units in the care of the frail elderly cancer
      patient.
AB  - BACKGROUND: Geriatric assessment has been suggested as a possibly useful approach
      in dealing with frail elderly cancer patients. METHODS: This was a secondary
      subset analysis from a randomized 2 x 2 factorial trial in 11 Department of
      Veterans Affairs medical centers. Hospitalized, frail patients at least 65 years
      old, after stabilization of their acute illness, were randomized to receive care
      in a geriatric inpatient unit, a geriatric outpatient clinic, both, or neither.
      The interventions involved core teams that provided geriatric assessment and
      patient management. We identified 99 patients with a diagnosis of cancer by The
      International Classification of Diseases, 9th Revision (ICD-9) codes, excluding
      all nonmelanoma skin cancers. Outcomes collected at discharge, 6 months, and 1
      year after randomization were survival, changes in health-related quality of life
      (using the Medical Outcomes Study 36-Item Short-Form general health survey [SF
      36]), activities of daily living, physical performance, health service
      utilization, and costs. RESULTS: There was no effect on mortality (1-year
      survival 59.6%). The changes in the SF-36 scores from randomization for emotional
      limitation, mental health and bodily pain (also sustained at 1 year) on the SF-36
      were better for geriatric inpatient care cancer patients at discharge. There was
      no difference in SF-36 scores between geriatric outpatient and usual outpatient
      care. Days of hospitalization and overall costs were equivalent for the
      interventions and usual care over the 1-year study. CONCLUSIONS: This study
      suggests that inpatient geriatric assessment and management may be an effective
      approach to the management of pain and psychological status in the elderly cancer
      inpatient at no greater length of hospitalization or extra cost than usual care.

PMID- 15983187
TI  - Stature prediction equations for elderly Hispanics in Latin American countries by
      sex and ethnic background.
AB  - BACKGROUND: We estimate prediction equations of stature from knee height for
      elderly Hispanic Blacks, Mulattos, Mestizos, Mexicans, and Whites. We test the
      predictive power of estimated equations, assess the magnitude of relative errors
      in measures of body mass index (BMI), quantify errors committed when using
      predicted rather that observed height, and evaluate the differences in the
      strength of the relation between BMI and diabetes. METHODS: Using data collected
      in 1999-2000, we split each sex and/or ethnic group into validation and cross
      validation groups, estimate equations from the validation groups, then test them
      on the cross-validation groups. We use robust linear regression to assess the sex
      and/or ethnic-specific relation between knee height and stature. We evaluate the
      accuracy of classifications by obesity and of estimates of risk of diabetes when
      using estimated versus observed height. RESULTS: Our equations are slightly less
      accurate than those obtained from U.S. data ( 4), although ethnic-specific
      parameters are comparable. Classification of subpopulations by obesity has high
      sensitivity and specificity. The estimated measure of BMI strongly attenuates
      estimated effects of obesity on diabetes. Thus, although the predicted heights
      fall within acceptable error bounds, their utilization in modeling relations to
      other health outcomes may give misleading inferences. CONCLUSIONS: Knee height is
      a good surrogate for current height for elderly populations. It is always
      preferable to use ethnic-specific predictions, because the relation differs by
      ethnicity. Great care has to be exercised when classifying populations using
      surrogate measures of height, or in estimating relations between measures that
      are functions of surrogate height and health outcomes.

PMID- 15983188
TI  - Nutritional epigenomics of metabolic syndrome: new perspective against the
      epidemic.
AB  - Human epidemiological studies and appropriately designed dietary interventions in
      animal models have provided considerable evidence to suggest that maternal
      nutritional imbalance and metabolic disturbances, during critical time windows of
      development, may have a persistent effect on the health of the offspring and may
      even be transmitted to the next generation. We now need to explain the mechanisms
      involved in generating such responses. The idea that epigenetic changes
      associated with chromatin remodeling and regulation of gene expression underlie
      the developmental programming of metabolic syndrome is gaining acceptance.
      Epigenetic alterations have been known to be of importance in cancer for
      approximately 2 decades. This has made it possible to decipher epigenetic codes
      and machinery and has led to the development of a new generation of drugs now in
      clinical trials. Although less conspicuous, epigenetic alterations have also been
      progressively shown to be relevant to common diseases such as atherosclerosis and
      type 2 diabetes. Imprinted genes, with their key roles in controlling feto
      placental nutrient supply and demand and their epigenetic lability in response to
      nutrients, may play an important role in adaptation/evolution. The combination of
      these various lines of research on epigenetic programming processes has
      highlighted new possibilities for the prevention and treatment of metabolic
      syndrome.

PMID- 15983189
TI  - Effect of fructose overfeeding and fish oil administration on hepatic de novo
      lipogenesis and insulin sensitivity in healthy men.
AB  - High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes
      hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin
      resistance may be secondary to alterations of lipid metabolism. In contrast, fish
      oil supplementation decreases triglycerides and may improve insulin resistance.
      Therefore, we studied the effect of high-fructose diet and fish oil on DNL and
      VLDL triglycerides and their impact on insulin resistance. Seven normal men were
      studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high
      fructose diet (corresponding to an extra 25% of total calories); fish oil plus
      high-fructose diet; and control conditions. Following each condition, fasting
      fractional DNL and endogenous glucose production (EGP) were evaluated using [1
      13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic
      clamp was performed to assess insulin sensitivity. High-fructose diet
      significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%),
      fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired
      insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but
      had no effect on whole- body insulin-mediated glucose disposal. Fish oil
      significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet
      compared with high-fructose diet without fish oil and tended to reduce DNL but
      had no other significant effect. In conclusion, high-fructose diet induced
      dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed
      dyslipidemia but not insulin resistance.

PMID- 15983190
TI  - Assessing the predictive accuracy of QUICKI as a surrogate index for insulin
      sensitivity using a calibration model.
AB  - The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear
      correlation with the glucose clamp index of insulin sensitivity (SI(Clamp)) that
      is better than that of many other surrogate indexes. However, correlation between
      a surrogate and reference standard may improve as variability between subjects in
      a cohort increases (i.e., with an increased range of values). Correlation may be
      excellent even when prediction of reference values by the surrogate is poor.
      Thus, it is important to evaluate the ability of QUICKI to accurately predict
      insulin sensitivity as determined by the reference glucose clamp method. In the
      present study, we used a calibration model to compare the ability of QUICKI and
      other simple surrogates to predict SI(Clamp). Predictive accuracy was evaluated
      by both root mean squared error of prediction as well as a more robust leave-one
      out cross-validation-type root mean squared error of prediction (CVPE). Based on
      data from 116 glucose clamps obtained from nonobese, obese, type 2 diabetic, and
      hypertensive subjects, we found that QUICKI and log (homeostasis model assessment
      [HOMA]) were both excellent at predicting SI(Clamp) (CVPE = 1.45 and 1.51,
      respectively) and significantly better than HOMA, 1/HOMA, and fasting insulin
      (CVPE = 3.17, P < 0.001; 1.67, P < 0.02; and 2.85, P < 0.001, respectively).
      QUICKI and log(HOMA) also had the narrowest distribution of residuals (measured
      SI(Clamp) - predicted SI(Clamp)). In a subset of subjects (n = 78) who also
      underwent a frequently sampled intravenous glucose tolerance test with minimal
      model analysis, QUICKI was significantly better than the minimal model index of
      insulin sensitivity (SI(MM)) at predicting SI(Clamp) (CVPE = 1.54 vs. 1.98, P =
      0.001). We conclude that QUICKI and log(HOMA) are among the most accurate
      surrogate indexes for determining insulin sensitivity in humans.

PMID- 15983191
TI  - A high-fat diet coordinately downregulates genes required for mitochondrial
      oxidative phosphorylation in skeletal muscle.
AB  - Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and
      reduced mitochondrial mass and function. We hypothesized a HFD may affect
      expression of genes involved in mitochondrial function and biogenesis. To test
      this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days
      with muscle biopsies before and after intervention. Oligonucleotide microarray
      analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni
      adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS)
      decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1,
      and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein
      SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1)
      alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01,
      respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks
      and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately
      90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these
      results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS
      and mitochondrial biogenesis. These changes mimic those observed in diabetes and
      insulin resistance and, if sustained, may result in mitochondrial dysfunction in
      the prediabetic/insulin-resistant state.

PMID- 15983192
TI  - A multicompartmental model of in vivo adipose tissue glycerol kinetics and
      capillary permeability in lean and obese humans.
AB  - Lipolysis of adipose tissue triglycerides releases glycerol. Twenty-four
      volunteers, of whom 6 were obese and 13 were women, received a primed-constant
      infusion of 2H5-glycerol for 120 min during postabsorptive steady-state
      conditions. Arterial, abdominal venous, and interstitial (microdialysis) samples
      were taken, and a four-compartment model was applied to assess subcutaneous
      abdominal adipose tissue glycerol kinetics. Adipose tissue blood flow was
      measured using 133Xe washout. Venous glycerol concentrations (median 230
      micromol/l [interquartile range 210-268]) were consistently greater than those of
      arterial blood (69.1 micromol/l [56.5-85.5]), while glycerol isotopic enrichments
      (tracer-to-tracee ratio) were greater in arterial blood (8.34% [7.44-10.1]) than
      venous blood (2.34% [1.71-2.69], P < 0.01). Microdialysate glycerol enrichment
      was 1.44% (1.11-1.79), indicating incomplete permeability of glycerol between
      capillary blood and interstitium. Calculated interstitial glycerol concentrations
      were between 270 micromol/l (256-350) and 332 micromol/l (281-371) (examining
      different boundary conditions). The calculated capillary diffusion capacity (ps)
      was between 2.21 ml . 100 g tissue(-1) . min(-1) (1.31-3.13) and 3.09 ml . 100 g
      tissue(-1) . min(-1) (1.52-4.90) and correlated inversely with adiposity (Rs< or
      = -0.45, P < 0.05). Our results support previous estimates of interstitial
      glycerol concentration within adipose tissue and reveal capillary diffusion
      capacity is reduced in obesity.

PMID- 15983193
TI  - Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis
      as well as gluconeogenesis.
AB  - To determine whether the hepatic insulin resistance of obesity and type 2
      diabetes is due to impaired insulin-induced suppression of glycogenolysis as well
      as gluconeogenesis, 10 lean nondiabetic, 10 obese nondiabetic, and 11 obese type
      2 diabetic subjects were studied after an overnight fast and during a
      hyperinsulinemic-euglycemic clamp. Gluconeogenesis and glycogenolysis were
      measured using the deuterated water method. Before the clamp, when glucose and
      insulin concentrations differed among the three groups, gluconeogenesis was
      higher in the diabetic than in the obese nondiabetic subjects (P < 0.05) and
      glycogenolysis was higher in the diabetic than in the lean nondiabetic subjects
      (P < 0.05). During the clamp, when glucose and insulin concentrations were
      matched and glucagon concentrations were suppressed, both glycogenolysis and
      gluconeogenesis were higher (P < 0.01) in the diabetic versus the obese and lean
      nondiabetic subjects. Furthermore, glycogenolysis and gluconeogenesis were higher
      (P < 0.01) in the obese than in the lean nondiabetic subjects. Plasma free fatty
      acid concentrations correlated (P < 0.001) with glucose production and
      gluconeogenesis both before and during the clamp and with glycogenolysis during
      the clamp (P < 0.01). We concluded that defects in the regulation of
      glycogenolysis as well as gluconeogenesis cause hepatic insulin resistance in
      obese nondiabetic and type 2 diabetic humans.

PMID- 15983194
TI  - Dual role of phosphofructokinase-2/fructose bisphosphatase-2 in regulating the
      compartmentation and expression of glucokinase in hepatocytes.
AB  - Hepatic glucokinase is regulated by a 68-kDa regulatory protein (GKRP) that is
      both an inhibitor and nuclear receptor for glucokinase. We tested the role of 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2) in regulating
      glucokinase compartmentation in hepatocytes. PFK2 catalyzes formation or
      degradation of the regulator of glycolysis fructose 2,6-bisphosphate (fructose
      2,6-P2), depending on its phosphorylation state (ser-32), and is also a
      glucokinase-binding protein. Incubation of hepatocytes at 25 mmol/l glucose
      causes translocation of glucokinase from the nucleus to the cytoplasm and an
      increase in fructose 2,6-P2. Glucagon caused phosphorylation of PFK2-ser-32,
      lowered the fructose 2,6-P2 concentration, and inhibited glucose-induced
      translocation of glucokinase. These effects of glucagon were reversed by
      expression of a kinase-active PFK2 mutant (S32A/H258A) that overrides the
      suppression of fructose 2,6-P2 but not by overexpression of wild-type PFK2.
      Overexpression of PFK2 potentiated glucokinase expression in hepatocytes
      transduced with an adenoviral vector-encoding glucokinase by a mechanism that
      does not involve stabilization of glucokinase protein from degradation. It is
      concluded that PFK2 has a dual role in regulating glucokinase in hepatocytes: it
      potentiates glucokinase protein expression by posttranscriptional mechanisms and
      favors its cytoplasmic compartmentation. Thus, it acts in a complementary
      mechanism to GKRP, which also regulates glucokinase protein expression and
      compartmentation.

PMID- 15983195
TI  - Impact of the liver-specific expression of SHIP2 (SH2-containing inositol 5'
      phosphatase 2) on insulin signaling and glucose metabolism in mice.
AB  - We investigated the role of hepatic SH2-containing inositol 5'-phosphatase 2
      (SHIP2) in glucose metabolism in mice. Adenoviral vectors encoding wild-type
      SHIP2 (WT-SHIP2) and a dominant-negative SHIP2 (DeltaIP-SHIP2) were injected via
      the tail vein into db/+m and db/db mice, respectively. Four days later, amounts
      of hepatic SHIP2 protein were increased by fivefold. Insulin-induced
      phosphorylation of Akt in liver was impaired in WT-SHIP2-expressing db/+m mice,
      whereas the reduced phosphorylation was restored in DeltaIP-SHIP2-expressing
      db/db mice. The abundance of mRNA for glucose-6-phosphatase (G6Pase) and PEPCK
      was increased, that for glucokinase (GK) was unchanged, and that for sterol
      regulatory element-binding protein 1 (SREBP)-1 was decreased in hepatic WT-SHIP2
      overexpressing db/+m mice. The increased expression of mRNA for G6Pase and PEPCK
      was partly suppressed, that for GK was further enhanced, and that for SREBP1 was
      unaltered by the expression of DeltaIP-SHIP2 in db/db mice. The hepatic
      expression did not affect insulin signaling in skeletal muscle and fat tissue in
      both mice. After oral glucose intake, blood glucose levels and plasma insulin
      concentrations were elevated in WT-SHIP2-expressing db/+m mice, while elevated
      values were decreased by the expression of DeltaIP-SHIP2 in db/db mice. These
      results indicate that hepatic SHIP2 has an impact in vivo on the glucose
      metabolism in both physiological and diabetic states possibly by regulating
      hepatic gene expression.

PMID- 15983196
TI  - The regulation of fatty acid synthase by STAT5A.
AB  - Growth hormone (GH) diminishes adipose tissue mass in vivo and decreases
      expression and activity of fatty acid synthase (FAS) in adipocytes. GH and
      prolactin (PRL) are potent activators of STAT5 and exert adipogenic and
      antiadipogenic effects in adipocytes. In this study, we demonstrate that GH and
      PRL decrease the mRNA and protein levels of FAS in 3T3-L1 adipocytes. We present
      evidence that indicates that FAS is repressed at the level of transcription. In
      addition, PRL responsiveness was shown to exist between -1,594 and -700 of the
      rat FAS promoter. Moreover, responsiveness to PRL was abolished with mutation of
      a site at position -908 to -893, which we have shown to bind STAT5A in a PRL
      dependent manner. Taken together, these data strongly suggest that PRL directly
      represses expression of FAS in adipocytes through STAT5A binding to the -908 to 
      893 site. Furthermore, our results indicate that STAT5A has an antilipogenic
      function in adipocytes and may contribute to the regulation of energy balance.

PMID- 15983197
TI  - Role of upstream stimulatory factors in regulation of renal transforming growth
      factor-beta1.
AB  - We previously identified an E-box to be implicated in high-glucose-induced
      transforming growth factor-beta1 (TGF-beta1) gene stimulation in murine mesangial
      cells. In the present study, we evaluated the role of upstream stimulatory
      factors (USFs) in mediating glucose-induced stimulation of TGF-beta1. Mesangial
      cells cultured in glucose concentrations exceeding 2.7 mmol/l D-glucose exhibited
      increased levels of USF1 and USF2 protein by Western analysis and electrophoretic
      mobility shift assay (EMSA). An E-box element from the murine TGF-beta1 promoter
      revealed USF1 and USF2 binding by EMSA. Chromatin immunoprecipitation assay
      revealed in vivo binding of USF1 to a glucose-responsive region of the TGF-beta1
      promoter. Transient cotransfection studies of 293 cells with USF1 led to a
      twofold increase in TGF-beta1 promoter activity and a 46% increase in secreted
      TGF-beta1 protein levels. Wild-type and USF2 knockout mice exhibited a 2.5-fold
      stimulation of renal TGF-beta1 expression upon fasting and refeeding with a
      carbohydrate-rich diet, whereas USF1 knockout mice exhibited only a minimal
      increase of renal TGF-beta1 upon refeeding. USF1 mRNA levels were increased in
      mouse kidneys with carbohydrate refeeding, and USF1 protein was increased in
      diabetic rat kidneys compared with controls. We conclude that USF1 is stimulated
      by modest increases in glucose concentration in murine mesangial cells, bind to
      the murine TGF-beta1 promoter, contribute to carbohydrate-induced renal TGF-beta1
      expression, and may play a role in diabetes-related gene regulation in the
      kidney.

PMID- 15983198
TI  - Distinct forebrain and caudal brainstem contributions to the neuropeptide Y
      mediation of ghrelin hyperphagia.
AB  - Neuropeptide Y (NPY) has been implicated in the downstream mediation of ghrelin
      hyperphagia, with the site of action for both peptides considered to be intrinsic
      to the hypothalamus. Here, however, we observed robust hyperphagia with caudal
      brainstem (CBS) (fourth intracerebroventricular) ghrelin delivery and, moreover,
      that this response was reversed with coadministration of either of two NPY
      receptor antagonists (1229U91 and D-Tyr27,36, D-Thr32 NPY27-36) with contrasting
      NPY receptor subtype-binding properties. The same results were obtained after
      forebrain (third intracerebroventricular) administration, but the sites for both
      ghrelin and antagonist action were open to question, given the caudal flow of
      cerebrospinal fluid (CSF) through the ventricular system. To control for this, we
      occluded the cerebral aqueduct to restrict CSF flow between the forebrain and CBS
      ventricles and tested all combinations (same and cross ventricle) of ghrelin (150
      pmol/1 microl) and NPY receptor antagonist delivery. With fourth
      intracerebroventricular ghrelin delivery after aqueduct occlusion,
      preadministration of either of the two antagonists through the same cannula
      reversed the hyperphagic response but neither was effective when delivered to the
      third ventricle. With third intracerebroventricular ghrelin administration,
      however, 1229U91 reversed the ingestive response only when delivered to the
      fourth ventricle, whereas D-Tyr27,36) D-Thr32 NPY27-36 was effective only when
      delivered to the forebrain. These results demonstrate distinct mediating pathways
      (due to location and subtypes of relevant NPY receptor) for the hyperphagic
      response driven separately by forebrain and CBS ghrelin administration.

PMID- 15983199
TI  - Long-term efficacy of leptin replacement in patients with generalized
      lipodystrophy.
AB  - Ectopic fat accumulation has been implicated as a contributing factor in the
      abnormal metabolic state of obesity. One human model of ectopic fat deposition is
      generalized lipodystrophy. Generalized lipodystrophy is a rare disorder
      characterized by a profound deficiency of adipose tissue with resultant loss of
      triglyceride storage capacity and reduced adipokines, including leptin. Subjects
      with generalized lipodystrophy and reduced leptin levels often have an increased
      appetite leading to hyperphagia. Excess fuel consumption, coupled with a lack of
      adipose tissue, contributes to the significant ectopic triglyceride accumulation
      in the muscle and liver seen in these subjects. This ectopic fat, along with the
      deficiency in leptin signaling and perhaps other adipokines, likely contributes
      to insulin resistance, diabetes, and hepatic steatosis. We report here the long
      term effects of leptin replacement in a cohort of these subjects. Fifteen
      patients with generalized lipodystrophy were treated with twice-daily recombinant
      methionyl human leptin (r-metHuLeptin) for 12 months. We evaluated metabolic
      parameters at baseline and every 4 months. Antidiabetes medications were
      decreased or discontinued as necessary. Reductions were seen in serum fasting
      glucose (from 205 +/- 19 to 126 +/- 11 mg/dl; P < 0.001), HbA1c (from 9 +/- 0.4
      to 7.1 +/- 0.5%; P < 0.001), triglycerides (from 1,380 +/- 500 to 516 +/- 236
      mg/dl; P < 0.001), LDL (from 139 +/- 16 to 85 +/- 7 mg/dl; P < 0.01), and total
      cholesterol (from 284 +/- 40 to 167 +/- 21 mg/dl; P < 0.01). HDL was unchanged
      (from 31 +/- 3 to 29 +/- 2 mg/dl; P = 0.9). Liver volumes were significantly
      reduced (from 3,663 +/- 326 to 2,190 +/- 159 cm3; P < 0.001), representing loss
      of steatosis. Decreases were seen in total body weight (from 61.8 +/- 3.6 to 57.4
      +/- 3.4 kg; P = 0.02) and resting energy expenditure (from 1,929 +/- 86 to 1,611
      +/- 101 kcal/24 h; P < 0.001). R-metHuLeptin led to significant and sustained
      improvements in glycemia, dyslipidemia, and hepatic steatosis. Leptin represents
      the first novel, effective, long-term treatment for severe forms of
      lipodystrophy.

PMID- 15983200
TI  - Autocrine action of adiponectin on human fat cells prevents the release of
      insulin resistance-inducing factors.
AB  - The adipocyte hormone adiponectin is negatively correlated with obesity and
      insulin resistance and may exert an important antidiabetes function. In this
      study, primary human skeletal muscle cells were cocultured with human fat cells
      or incubated with adipocyte-conditioned medium in the presence or absence of the
      globular domain of adiponectin (gAcrp30) to analyze its capacity to restore
      normal insulin signaling in the muscle cells. Human skeletal muscle cells
      cocultured with adipocytes or treated with adipocyte-conditioned medium showed an
      impaired Akt and glycogen synthase kinase 3 serine phosphorylation in response to
      insulin. Furthermore, insulin-stimulated GLUT4 translocation was reduced by
      adipocyte-conditioned medium. Impaired insulin signaling was normalized upon
      addition of gAcrp30 to the coculture. Further, adipocyte-conditioned medium
      generated in the presence of gAcrp30 was unable to perturb insulin-stimulated Akt
      phosphorylation. Concomitant addition of gAcrp30 and adipocyte-conditioned medium
      to the myocytes failed to restore normal insulin action. Protein array analysis
      of adipocyte-conditioned medium indicated that the secretion of at least eight
      different cytokines was diminished in response to gAcrp30. We therefore suggest
      that adiponectin operates as a key regulator of adipocyte secretory function.
      This autocrine action may prevent the induction of skeletal muscle insulin
      resistance and may partly explain the antidiabetes action of this hormone.

PMID- 15983201
TI  - Role of selective leptin resistance in diet-induced obesity hypertension.
AB  - Leptin is an adipocyte-derived hormone that plays a key role in the regulation of
      body weight through its actions on appetite and metabolism. Leptin also increases
      sympathetic nerve activity (SNA) and blood pressure. We tested the hypothesis
      that diet-induced obesity is associated with resistance to the metabolic actions
      of leptin but preservation of its renal SNA and arterial pressure effects,
      leading to hypertension. Mice were fed a high-fat diet for 10 weeks to induce
      moderate obesity. The decrease in food intake and body weight induced by
      intraperitoneal or intracerebroventricular leptin was significantly attenuated in
      the obese mice. Regional SNA responses to leptin were differentially altered in
      diet-induced obese mice. Renal SNA response to leptin was preserved, whereas
      lumbar and brown adipose tissue SNA responses were attenuated in obese mice.
      Radiotelemetric arterial pressure was approximately 10 mmHg higher in obese mice.
      Furthermore, the increase in arterial pressure in response to long-term (12 days)
      leptin treatment was preserved in obese mice. Thus, mice with diet-induced
      obesity exhibit circulating hyperleptinemia and resistance to the metabolic
      actions of leptin. However, there is preservation of the renal sympathetic and
      arterial pressure responses to leptin, which represent a potential mechanism for
      the adverse cardiovascular consequences of obesity.

PMID- 15983202
TI  - NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity.
AB  - Although it is well established that B-cells are required for the development of
      diabetes in the nonobese diabetic (NOD) mouse, the nature of their role remains
      unknown. Herein, we investigate the hypothesis that B-cells in this autoimmune
      background actively disrupt the tolerant state of those T-cells with which they
      interact. We demonstrate that NOD B-cells express elevated levels of crucial
      molecules involved in antigen presentation (including CD21/35, major
      histocompatibility complex class II, and CD40), alterations that invite the
      possibility of inappropriate T-cell activation. However, when chimeric animals
      are generated in which all B-cells are NOD-derived, a tolerant state is
      maintained. These data demonstrate that although B-cells are required for the
      development of autoimmunity, they are not sufficient to disrupt established
      tolerance. Moreover, non-B-cell antigen-presenting cells may be the critical
      actors in the establishment of the tolerant state; this function may be absent in
      NOD mice as they are characterized by deficient professional antigen-presenting
      cell function.

PMID- 15983203
TI  - Maternal factors in a model of type 1 diabetes differentially affect the
      development of insulitis and overt diabetes in offspring.
AB  - Type 1 diabetes, a multifactorial disease involving genetic and environmental
      factors, results from the destruction of pancreatic beta-cells. The maternal
      environment has been suggested to be important in the development of diabetes. To
      assess the role of maternal factors in the development of insulitis and overt
      diabetes, we transplanted pre-implantation stage embryos of nonobese diabetic
      (NOD) mice, a model of type 1 diabetes, into the uterus of each recipient.
      Recipients were ICR and DBA/2J mice without diabetic genetic predisposition and
      NOD mice not exhibiting overt diabetes during the experiment; offspring were
      designated as NOD/ICR, NOD/DBA, and NOD/NOD, respectively; unmanipulated NOD
      offspring were also examined. NOD/ICR and NOD/DBA offspring developed insulitis
      significantly earlier than NOD/NOD offspring. However, overt diabetes was
      significantly suppressed in NOD/ICR and NOD/DBA offspring in comparison with
      NOD/NOD offspring. Insulin autoantibodies (IAAs) were undetectable in ICR and
      DBA/2J surrogate mothers and in NOD/ICR and NOD/DBA offspring at the onset of
      insulitis, suggesting that maternal factors other than transmitted IAAs induced
      the earlier onset. The present study indicates that altered maternal factors
      modify the immune response to islets, which in turn might affect the pathogenic
      course from insulitis to overt diabetes.

PMID- 15983204
TI  - The influence of the major histocompatibility complex on development of
      autoimmune diabetes in RIP-B7.1 mice.
AB  - The most important genetic susceptibility factor for type 1 diabetes is encoded
      in the major histocompatibility complex (MHC). The nonobese diabetic (NOD) mouse,
      which develops spontaneous diabetes, expresses H-2g7 comprising the MHC class I
      molecules Kd and Db and the MHC class II molecule I-Ag7. However, neither B6.H
      2g7 mice, in which H-2g7 is expressed on the C57BL/6 genetic background, nor the
      nonobese resistant (NOR) mouse, in which H-2g7 is expressed on a genetic
      background that is 88% similar to NOD mice, develop diabetes. Immune tolerance
      can be broken in these diabetes-resistant mice expressing H-2g7 if the
      costimulatory molecule B7.1 is present on the islet beta cells. This does not
      occur if only single MHC class I components of the H-2g7 haplotype are present,
      such as Kd in BALB/c mice or Db in C57BL/6 mice, both of which develop only a low
      level of diabetes when B7.1 is expressed. The presence of I-Ag7 leads to the
      development of an autoimmune T-cell repertoire, and local costimulation of CD8 T
      cells precipitates aggressive diabetes. This implies that a major role of the MHC
      class II molecules in diabetes is the development of an autoreactive T-cell
      repertoire.

PMID- 15983205
TI  - Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the
      development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm
      rat.
AB  - The IDDM (LEW.1AR1/Ztm-iddm) rat is a type 1 diabetic animal model characterized
      by a rapid apoptotic pancreatic beta-cell destruction. Here we have analyzed the
      time course of islet infiltration, changes in the cytokine expression pattern,
      and beta-cell apoptosis in the transition from the pre-diabetic to the diabetic
      state. Transition from normoglycemia to hyperglycemia occurred when beta-cell
      loss exceeded 60-70%. At the early stages of islet infiltration, macrophages were
      the predominant immune cell type in the peripherally infiltrated islets.
      Progression of beta-cell loss was closely linked to a severe infiltration of the
      whole islet by CD8+ T-cells. With progressive islet infiltration, interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were expressed in
      immune cells but not in beta-cells. This proinflammatory cytokine expression
      pattern coincided with the expression of inducible nitric oxide synthase (iNOS)
      and procaspase 3 in beta-cells and a peak apoptosis rate of 6.7%. Islet
      infiltration declined after manifestation of clinical diabetes, yielding end
      stage islets devoid of beta-cells and immune cells without any sign of cytokine
      expression. The observed coincidence of IL-1beta and TNF-alpha expression in the
      immune cells and the induction of iNOS and procaspase 3 mRNA expression in the
      beta-cells depicts a sequence of pathological changes leading to apoptotic beta
      cell death in the IDDM rat. This chain of events provides a mechanistic
      explanation for the development of the diabetic syndrome in this animal model of
      human type 1 diabetes.

PMID- 15983206
TI  - Identification of naturally processed HLA-A2--restricted proinsulin epitopes by
      reverse immunology.
AB  - Type 1 diabetes is thought to result from the destruction of beta-cells by
      autoantigen-specific T-cells. Observations in the NOD mouse model suggest that
      CD8+ cytotoxic T-cells play an essential role in both the initial triggering of
      insulitis and its destructive phase. However, little is known about the epitopes
      derived from human beta-cell autoantigens and presented by HLA class I molecules.
      We used a novel reverse immunology approach to identify HLA-A2-restricted,
      naturally processed epitopes derived from proinsulin, an autoantigen likely to
      play an important role in the pathogenesis of type 1 diabetes. Recombinant human
      proinsulin was digested with purified proteasome complexes to establish an
      inventory of potential COOH-terminals of HLA class I-presented epitopes. Cleavage
      data were then combined with epitope predictions based on the SYFPEITHI and BIMAS
      algorithms to select 10 candidate epitopes; 7 of these, including 3 with a
      sequence identical to murine proinsulin, were immunogenic in HLA-A2 transgenic
      mice. Moreover, six of six tested peptides were processed and presented by
      proinsulin-expressing cells. These results demonstrate the power of reverse
      immunology approaches. Moreover, the novel epitopes may be of significant
      interest in monitoring autoreactive T-cells in type 1 diabetes.

PMID- 15983207
TI  - Five-year follow-up after clinical islet transplantation.
AB  - Islet transplantation can restore endogenous beta-cell function to subjects with
      type 1 diabetes. Sixty-five patients received an islet transplant in Edmonton as
      of 1 November 2004. Their mean age was 42.9 +/- 1.2 years, their mean duration of
      diabetes was 27.1 +/- 1.3 years, and 57% were women. The main indication was
      problematic hypoglycemia. Forty-four patients completed the islet transplant as
      defined by insulin independence, and three further patients received >16,000
      islet equivalents (IE)/kg but remained on insulin and are deemed complete. Those
      who became insulin independent received a total of 799,912 +/- 30,220 IE (11,910
      +/- 469 IE/kg). Five subjects became insulin independent after one transplant.
      Fifty-two patients had two transplants, and 11 subjects had three transplants. In
      the completed patients, 5-year follow-up reveals that the majority (
      approximately 80%) have C-peptide present post-islet transplant, but only a
      minority ( approximately 10%) maintain insulin independence. The median duration
      of insulin independence was 15 months (interquartile range 6.2-25.5). The HbA(1c)
      (A1C) level was well controlled in those off insulin (6.4% [6.1-6.7]) and in
      those back on insulin but C-peptide positive (6.7% [5.9-7.5]) and higher in those
      who lost all graft function (9.0% [6.7-9.3]) (P < 0.05). Those who resumed
      insulin therapy did not appear more insulin resistant compared with those off
      insulin and required half their pretransplant daily dose of insulin but had a
      lower increment of C-peptide to a standard meal challenge (0.44 +/- 0.06 vs. 0.76
      +/- 0.06 nmol/l, P < 0.001). The Hypoglycemic score and lability index both
      improved significantly posttransplant. In the 128 procedures performed, bleeding
      occurred in 15 and branch portal vein thrombosis in 5 subjects. Complications of
      immunosuppressive therapy included mouth ulcers, diarrhea, anemia, and ovarian
      cysts. Of the 47 completed patients, 4 required retinal laser photocoagulation or
      vitrectomy and 5 patients with microalbuminuria developed macroproteinuria. The
      need for multiple antihypertensive medications increased from 6% pretransplant to
      42% posttransplant, while the use of statin therapy increased from 23 to 83%
      posttransplant. There was no change in the neurothesiometer scores pre- versus
      posttransplant. In conclusion, islet transplantation can relieve glucose
      instability and problems with hypoglycemia. C-peptide secretion was maintained in
      the majority of subjects for up to 5 years, although most reverted to using some
      insulin. The results, though promising, still point to the need for further
      progress in the availability of transplantable islets, improving islet
      engraftment, preserving islet function, and reducing toxic immunosuppression.

PMID- 15983208
TI  - Saturated and cis/trans unsaturated acyl CoA esters differentially regulate wild
      type and polymorphic beta-cell ATP-sensitive K+ channels.
AB  - Metabolic regulation of pancreatic beta-cell ATP-sensitive K+ channel (K(ATP)
      channel) function plays a key role in the process of glucose-stimulated insulin
      secretion (GSIS). Modulation of K(ATP) channel activity by long-chain acyl CoAs
      represents an important endogenous regulatory mechanism. Elevated acyl CoA levels
      have been reported in obese and type 2 diabetic individuals and may contribute to
      reduced beta-cell excitability and impaired GSIS. Recent studies suggest that the
      composition of dietary fat may influence the effects of high-fat feeding on
      impaired GSIS. Therefore, we examined the effects of side-chain length and the
      degree of saturation of various acyl CoAs on K(ATP) channel activity. Macroscopic
      currents from either wild-type or polymorphic (Kir6.2[E23K/I337V]) recombinant
      beta-cell K(ATP) channels were measured in inside-out patches by exposing the
      inner surface of the membrane to acyl CoAs at physiological nanomolar
      concentrations. Acyl CoAs increased both wild-type and polymorphic K(ATP) channel
      activity with the following rank order of efficacy: C18:0, C18:1trans
      approximately C18:1cis, C20:4 = C16:0, C16:1, and C18:2. A significant
      correlation exists between activation and acyl CoA hydrophobicity, suggesting
      that both side-chain length and degree of saturation are critical determinants of
      K(ATP) channel activation. Our observations reveal a plausible mechanism behind
      the disparate effects of acyl CoA saturation on K(ATP) channel activation and
      suggest that dietary fat composition may determine the severity of impaired GSIS
      via differential activation of beta-cell K(ATP) channels.

PMID- 15983209
TI  - Role for beta1 integrin and its associated alpha3, alpha5, and alpha6 subunits in
      development of the human fetal pancreas.
AB  - The integrin receptors play a major role in tissue morphogenesis and homeostasis
      by regulating cell interactions with extracellular matrix proteins. We have
      examined the expression pattern of integrin subunits in the human fetal pancreas
      (8-20 weeks fetal age) and the relevance of beta1 integrin function for insulin
      gene expression and islet cell survival. Its subunits alpha3, alpha5, and alpha6
      beta1 integrins are expressed in ductal cells at 8 weeks, before glucagon- and
      insulin-immunoreactive cells bud off; their levels gradually increase in both
      ductal cells and islet clusters up to 20 weeks. Colocalization of alpha3, alpha5
      and alpha6 beta1 integrins with endocrine cell markers was frequently observed in
      8- to 20-week fetal pancreatic cells. When the beta1 integrin receptor was
      functionally blocked in cultured islet-epithelial clusters with a beta1
      immunoneutralizing antibody or following transient beta1 integrin small
      interfering RNA treatment, there was inhibition of cell adhesion to extracellular
      matrices, decreased expression of insulin, and increased cell apoptosis. These
      data offer evidence for dynamic and cell-specific changes in integrin expression
      during human pancreatic islet neogenesis. They also provide an initial insight
      into a molecular basis for cell-matrix interactions during islet development and
      suggest that beta1 integrin plays a vital role in regulating islet cell adhesion,
      gene expression, and survival.

PMID- 15983210
TI  - Targeted inactivation of hepatocyte growth factor receptor c-met in beta-cells
      leads to defective insulin secretion and GLUT-2 downregulation without alteration
      of beta-cell mass.
AB  - Overexpression of hepatocyte growth factor (HGF) in the beta-cell of transgenic
      mice enhances beta-cell proliferation, survival, and function. In the current
      studies, we have used conditional ablation of the c-met gene to uncover the
      physiological role of HGF in beta-cell growth and function. Mice in which c-met
      is inactivated in the beta-cell (MetCKO mice) display normal body weight, blood
      glucose, and plasma insulin compared with control littermates. In contrast,
      MetCKO mice displayed significantly diminished glucose tolerance and reduced
      plasma insulin after a glucose challenge in vivo. This impaired glucose tolerance
      in MetCKO mice was not caused by insulin resistance because sensitivity to
      exogenous insulin was similar in both groups. Importantly, in vitro glucose
      stimulated insulin secretion in MetCKO islets was decreased by approximately 50%
      at high glucose concentrations compared with control islets. Furthermore, whereas
      insulin and glucokinase expression in MetCKO islets were normal, GLUT-2
      expression was decreased by approximately 50%. These changes in beta-cell
      function in MetCKO mice were not accompanied by changes in total beta-cell mass,
      islet morphology, islet cell composition, and beta-cell proliferation.
      Interestingly, however, MetCKO mice display an increased number of small islets,
      mainly single and doublet beta-cells. We conclude that HGF/c-met signaling in the
      beta-cell is not essential for beta-cell growth, but it is essential for normal
      glucose-dependent insulin secretion.

PMID- 15983211
TI  - Peptide-mediated targeting of the islets of Langerhans.
AB  - Strategies for restoring beta-cell function in diabetic patients would be greatly
      aided by the ability to target genes, proteins, or small molecules specifically
      to these cells. Furthermore, the ability to direct imaging agents specifically to
      beta-cells would facilitate diagnosis and monitoring of disease progression. To
      isolate ligands that can home to beta-cells in vivo, we have panned a random
      phage-displayed 20-mer peptide library on freshly isolated rat islets. We have
      isolated two 20-mer peptides that bind to islets ex vivo. One of these peptides
      preferentially homes to the islets of Langerhans in a normal rat with clear
      differentiation between the endocrine and exocrine cells of the pancreas.
      Furthermore, this peptide does not target beta-cells in a type 2 diabetes animal
      model, suggesting that the peptide can discriminate between glucose-stimulated
      insulin secretion-functional and -dysfunctional beta-cells.

PMID- 15983212
TI  - Overexpression of glutathione peroxidase with two isoforms of superoxide
      dismutase protects mouse islets from oxidative injury and improves islet graft
      function.
AB  - Primary nonfunction of transplanted islets results in part from their sensitivity
      to reactive oxygen species (ROS) generated during the isolation and
      transplantation process. Our aim was to examine whether coexpression of
      antioxidant enzymes to detoxify multiple ROS increased the resistance of mouse
      islets to oxidative stress and improved the initial function of islet grafts.
      Islets from transgenic mice expressing combinations of human copper/zinc
      superoxide dismutase (SOD), extracellular SOD, and cellular glutathione
      peroxidase (Gpx-1) were subjected to oxidative stress in vitro. Relative
      viability after hypoxanthine/xanthine oxidase treatment was as follows:
      extracellular SOD + Gpx-1 + Cu/Zn SOD > extracellular SOD + Gpx-1 > extracellular
      SOD > wild type. Expression of all three enzymes was the only combination
      protective against hypoxia/reoxygenation. Islets from transgenic or control wild
      type mice were then transplanted into streptozotocin-induced diabetic recipients
      in a syngeneic marginal islet mass model, and blood glucose levels were monitored
      for 7 days. In contrast to single- and double-transgenic grafts, triple
      transgenic grafts significantly improved control of blood glucose compared with
      wild type. Our results indicate that coexpression of antioxidant enzymes has a
      complementary beneficial effect and may be a useful approach to reduce primary
      nonfunction of islet grafts.

PMID- 15983213
TI  - Aberrant processing of human proislet amyloid polypeptide results in increased
      amyloid formation.
AB  - The amyloid present in the islets of Langerhans in type 2 diabetes is polymerized
      islet amyloid polypeptide (IAPP). The precursor protein proIAPP is
      posttranslationally modified, a process involving the removal of NH2- and COOH
      terminal flanking peptides. This step is performed by the prohormone convertases
      PC2 and PC1/3. PC2 processes proIAPP preferably at the NH2-terminal processing
      site, and PC1/3 processes proIAPP exclusively at the COOH-terminal site. Little
      is known regarding the exact circumstances leading to islet amyloid formation. In
      this study, we have examined the possible significance of aberrant processing of
      proIAPP on amyloid formation in several in vitro cellular systems. In our
      studies, human (h)-proIAPP was transfected into beta-TC-6 cells expressing both
      prohormone convertases and in which proIAPP is processed into IAPP. Additionally,
      h-proIAPP was transfected into three different pituitary-derived cell lines with
      different prohormone convertase profiles: AtT-20 cells (deficient in PC2), GH3
      cells (deficient in PC1/3), and GH4C1 cells (deficient in both convertases). We
      followed the processing of h-proIAPP with antibodies specific for the respective
      cleavage sites and stained the cells with Congo red to verify the accumulation of
      amyloid. Incomplete processing of h-proIAPP that occurs in AtT-20 and GH4C1 cells
      resulted in the formation of intracellular amyloid. No amyloid developed in beta
      TC-6 and GH3 cells lines with full processing of proIAPP. An intracellular
      increase in proIAPP and/or its metabolic products may thus promote intracellular
      amyloid formation, thereby causing cell death. When extracellularly exposed, this
      amyloid might act as template for continuing amyloid formation from processed
      IAPP released from the surrounding beta-cells.

PMID- 15983214
TI  - Inhibition of purinoceptors amplifies glucose-stimulated insulin release with
      removal of its pulsatility.
AB  - External ATP has been proposed to be an autocrine regulator of glucose-stimulated
      insulin secretion and responsible for the synchronization of the Ca2+ rhythmicity
      in the beta-cells required for a pulsatile release of insulin from the pancreas.
      The importance of external ATP for glucose-stimulated insulin release was
      evaluated in rats with the aid of 2-deoxy-N-methyladenosine-3,5-bisphosphate (MRS
      2179), an inhibitor of the purinoceptors known to affect the Ca2+ signaling in
      beta-cells. The concentration of cytoplasmic Ca2+ was measured in single beta
      cells and small aggregates with ratiometric fura-2 technique and the release of
      insulin recorded from isolated islets and the perfused pancreas. Addition of 1
      micromol/l ATP induced premature cytoplasmic Ca2+ concentration ([Ca2+]i)
      oscillations similar to those found in beta-cells exposed to 20 mmol/l glucose.
      In most experiments, the presence of 10 micromol/l MRS 2179 did not remove the
      glucose-induced [Ca2+]i rhythmicity in single beta-cells or the synchronization
      seen in coupled cells. Nevertheless, the same concentration of MRS 2179 promptly
      interrupted the pulsatility (frequency 0.22 +/- 0.01/min) of insulin secretion,
      raising the total amounts released from the pancreas. Prolonged exposure of
      islets to 1 and 10 micromol/l MRS 2179 enhanced insulin secretion at 20 mmol/l
      glucose 33% (P < 0.05) and 63% (P < 0.01), respectively, without affecting the
      release at 3 mmol/l glucose. The results support the idea that neural ATP signals
      entrain the islets into a common rhythm resulting in pulsatile release of insulin
      and that glucose stimulation of the secretory activity is counteracted by
      accumulation of inhibitory ATP around the beta-cells.

PMID- 15983215
TI  - Redox control of exocytosis: regulatory role of NADPH, thioredoxin, and
      glutaredoxin.
AB  - Cellular redox state is an important metabolic variable, influencing many aspects
      of cell function like growth, apoptosis, and reductive biosynthesis. In this
      report, we identify NADPH as a candidate signaling molecule for exocytosis in
      neuroendocrine cells. In pancreatic beta-cells, glucose acutely raised the NADPH
      to-NADP+ ratio and stimulated insulin release in parallel. Furthermore,
      intracellular addition of NADPH directly stimulated exocytosis of insulin
      granules. Effects of NADPH on exocytosis are proposed to be mediated by the redox
      proteins glutaredoxin (GRX) and thioredoxin (TRX) on the basis of the following
      evidence: 1) Expression of GRX mRNA is very high in beta-cells compared with
      other studied tissues, and GRX protein expression is high in islets and in brain;
      2) GRX and TRX are localized in distinct microdomains in the cytosol of beta
      cells; and 3) microinjection of recombinant GRX potentiated effects of NADPH on
      exocytosis, whereas TRX antagonized the NADPH effect. We propose that the
      NADPH/GRX/TRX redox regulation mediates a novel signaling pathway of nutrient
      induced insulin secretion.

PMID- 15983216
TI  - Tissue factor as a link between wounding and tissue repair.
AB  - The initial phase of wound repair involves inflammation, induction of tissue
      factor (TF), formation of a fibrin matrix, and growth of new smooth muscle actin
      (alpha-SMA)-positive vessels. In diabetes, TF induction in response to cutaneous
      wounding, which ordinarily precedes increased expression of vascular endothelial
      growth factor (VEGF) and alpha-SMA transcription, is diminished, though not to a
      degree causing excessive local bleeding. Enhanced TF expression in wounds of
      diabetic mice caused by somatic TF gene transfer increased VEGF transcription and
      translation and, subsequently, enhanced formation of new blood vessels and
      elevated blood flow. Furthermore, increased levels of TF in wounds of diabetic
      mice enhanced wound healing; the time to achieve 50% wound closure was reduced
      from 5.5 days in untreated diabetic mice to 4.1 days in animals undergoing TF
      gene transfer (this was not statistically different from wound closure in
      nondiabetic mice). Thus, cutaneous wounds in diabetic mice display a relative
      deficiency of TF compared with nondiabetic controls, and this contributes to
      delayed wound repair. These data establish TF expression as an important link
      between the early inflammatory response to cutaneous wounding and reparative
      processes.

PMID- 15983217
TI  - Impaired arachidonic acid-mediated activation of large-conductance Ca2+-activated
      K+ channels in coronary arterial smooth muscle cells in Zucker Diabetic Fatty
      rats.
AB  - We studied the arachidonic acid (AA)-mediated modulation of large-conductance
      Ca2+-activated K+ (BK) channels in coronary arterial smooth myocytes from lean
      control and Zucker Diabetic Fatty (ZDF) rats. A total of 1 micromol/l AA enhanced
      BK current by 274% in lean and by 98% in ZDF rats. After incubation with 10
      micromol/l indomethacin, 1 micromol/l AA increased BK currents by 80% in lean and
      by 70% in ZDF rats. Vasoreactivity studies showed that the dilation of small
      coronary arteries produced by 1 micromol/l AA was reduced by 44% in ZDF rats.
      [3H]6-keto-prostagladin F1alpha ([3H]6-keto-PGF1alpha,), the stable metabolite of
      prostacyclin (PGI2), was the major [3H]AA metabolite produced by coronary
      arteries of lean vessels, but ZDF vessels produced only 15% as much [3H]6-keto
      PGF1alpha. BK channel activation and vasorelaxation by iloprost were similar in
      lean and ZDF rats. Immunoblots showed a 73% reduction in PGI2 synthase (PGIS)
      expression in ZDF vessels compared with lean vessels, and there was no change in
      cyclooxygenase (COX) and BK channel expressions. Real-time PCR studies showed
      that mRNA levels of PGIS, COX-1, and COX-2 were similar between lean and ZDF
      vessels. We conclude that PGI2 is the major AA metabolite in lean coronaries, and
      AA-mediated BK channel activation is impaired in ZDF coronaries due to reduced
      PGIS activity.

PMID- 15983218
TI  - The early natural history of nephropathy in Type 1 Diabetes: III. Predictors of 5
      year urinary albumin excretion rate patterns in initially normoalbuminuric
      patients.
AB  - Predictors of albumin excretion rate (AER) abnormalities could provide earlier
      indicators of diabetic nephropathy risk. Data from the Natural History Study, a
      prospective 5-year observation of renal structure and function in young type 1
      diabetic patients, were examined for predictors of AER patterns in
      normoalbuminuric type 1 diabetic patients. Included were 170 patients (96
      females) (aged 16.7 +/- 5.9 years, duration of diabetes 8.0 +/- 4.3 years) with
      normal blood pressure, normoalbuminuria (AER <20 microg/min), and eight or more
      follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were
      determined quarterly and glomerular filtration rate (GFR) annually. Persistent
      microalbuminuria (PMA) was defined as 20-200 microg/min in two of three
      consecutive values within 6-12 months. Four different AER patterns were
      identified. Group 1 (n = 99): all values <20 microg/min. Group 2 (n = 49):
      intermittent levels >20 microg/min but not meeting microalbuminuria criteria.
      Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group
      4 (n = 8): microalbuminuria at study exit. Group 4 (497 +/- 95 nm, P < 0.01) and
      group 3 (464 +/- 113 nm, P = 0.03) patients had greater baseline glomerular
      basement membrane (GBM) width versus group 1 (418 +/- 67 nm). Baseline GFR in
      group 4 (163 +/- 37 ml.min(-1). 1.73 m(-2)) was higher than group 1 (143 +/- 28
      ml.min(-1) . 1.73 m(-2), P = 0.04). A1C was higher in group 2 (9.0 +/- 1.2%) than
      group 1 (8.4 +/- 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR
      were predictors of PMA. Since 64% of the patients that developed microalbuminuria
      reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by
      current microalbuminuria criteria is unclear.

PMID- 15983219
TI  - Heparanase-1 gene expression and regulation by high glucose in renal epithelial
      cells: a potential role in the pathogenesis of proteinuria in diabetic patients.
AB  - The molecular mechanisms of heparan sulfate proteoglycan downregulation in the
      glomerular basement membrane (GBM) of the kidneys with diabetic nephropathy
      remain controversial. In the present study, we showed that the expression of
      heparanase-1 (HPR1), a heparan sulfate-degrading endoglycosidase, was upregulated
      in the renal epithelial cells in the kidney with diabetic nephropathy. Urinary
      HPR1 levels were elevated in patients with diabetic nephropathy. In vitro cell
      culture studies revealed that HPR1 promoter-driven luciferase reporter gene
      expression, HPR1 mRNA, and protein were upregulated in renal epithelial cells
      under high glucose conditions. Induction of HPR1 expression by high glucose led
      to decreased cell surface heparan sulfate expression. HPR1 inhibitors were able
      to restore cell surface heparan sulfate expression. Functional analysis revealed
      that renal epithelial cells grown under high glucose conditions resulted in an
      increase of basement membrane permeability to albumin. Our studies suggest that
      loss of heparan sulfate in the GBM with diabetic nephropathy is attributable to
      accelerated heparan sulfate degradation by increased HPR1 expression.

PMID- 15983220
TI  - Metformin prevents high-glucose-induced endothelial cell death through a
      mitochondrial permeability transition-dependent process.
AB  - Hyperglycemia-induced oxidative stress is detrimental for endothelial cells,
      contributing to the vascular complications of diabetes. The mitochondrial
      permeability transition pore (PTP) is an oxidative stress-sensitive channel
      involved in cell death; therefore, we have examined its potential role in
      endothelial cells exposed to oxidative stress or high glucose level. Metformin,
      an antihyperglycemic agent used in type 2 diabetes, was also investigated because
      it inhibits PTP opening in transformed cell lines. Cyclosporin A (CsA), the
      reference PTP inhibitor, and a therapeutic dose of metformin (100 micromol/l) led
      to PTP inhibition in permeabilized human microvascular endothelial cells (HMEC
      1). Furthermore, exposure of intact HMEC-1 or primary endothelial cells from
      either human umbilical vein or bovine aorta to the oxidizing agent tert
      butylhydroperoxide or to 30 mmol/l glucose triggered PTP opening, cytochrome c
      decompartmentalization, and cell death. CsA or metformin prevented all of these
      effects. The antioxidant N-acetyl-l-cysteine also prevented hyperglycemia-induced
      apoptosis. We conclude that 1) elevated glucose concentration leads to an
      oxidative stress that favors PTP opening and subsequent cell death in several
      endothelial cell types and 2) metformin prevents this PTP opening-related cell
      death. We propose that metformin improves diabetes-associated vascular disease
      both by lowering blood glucose and by its effect on PTP regulation.

PMID- 15983221
TI  - The effect of ruboxistaurin on visual loss in patients with moderately severe to
      very severe nonproliferative diabetic retinopathy: initial results of the Protein
      Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter
      randomized clinical trial.
AB  - The purpose of this study was to evaluate the Safety and efficacy of the orally
      administered protein kinase C (PKC) beta isoform-selective inhibitor
      ruboxistaurin (RBX) in subjects with moderately severe to very severe
      nonproliferative diabetic retinopathy (NPDR). In this multicenter, double-masked,
      randomized, placebo-controlled study, 252 subjects received placebo or RBX (8,
      16, or 32 mg/day) for 36-46 months. Patients had an Early Treatment Diabetic
      Retinopathy Study (ETDRS) retinopathy severity level between 47B and 53E
      inclusive, an ETDRS visual acuity of 20/125 or better, and no history of scatter
      (panretinal) photocoagulation. Efficacy measures included progression of DR,
      moderate visual loss (MVL) (doubling of the visual angle), and sustained MVL
      (SMVL). RBX was well tolerated without significant adverse effects but had no
      significant effect on the progression of DR. Compared with placebo, 32 mg/day RBX
      was associated with a delayed occurrence of MVL (log rank, P = 0.038) and of SMVL
      (P = 0.226). RBX reduction of SMVL was evident only in eyes with definite
      diabetic macular edema at baseline (10% 32 mg/day RBX vs. 25% placebo, P =
      0.017). In multivariable Cox proportional hazard analysis, 32 mg/day RBX
      significantly reduced the risk of MVL compared with placebo (hazard ratio 0.37
      [95% CI 0.17-0.80], P = 0.012). In this clinical trial, RBX was well tolerated
      and reduced the risk of visual loss but did not prevent DR progression.

PMID- 15983222
TI  - Advanced glycation end product precursors impair ABCA1-dependent cholesterol
      removal from cells.
AB  - Abnormal HDL metabolism may contribute to the increased atherosclerosis
      associated with diabetes. The ATP-binding cassette transporter A1 (ABCA1) is an
      atheroprotective cell protein that mediates cholesterol transport from cells to
      apolipoprotein (apo) A-I, the major protein in HDL. Because formation of advanced
      glycation end products (AGEs) is associated with diabetic vascular complications,
      we examined the effects of carbonyls implicated in AGE formation on the ABCA1
      pathway in cultured fibroblasts and macrophages. Treating cells with
      glycolaldehyde (GA) and glyoxal (GO) strongly inhibited ABCA1-dependent transport
      of cholesterol from cells to apoA-I, while methylglyoxal had little effect. This
      occurred under conditions where other lipoprotein receptors or lipid metabolic
      pathways were little affected, indicating that ABCA1 was uniquely sensitive to
      these carbonyls. GA and GO destabilized ABCA1 and nearly abolished its binding of
      apoA-I, indicating that these carbonyls directly modified ABCA1. Immunohistology
      of coronary arteries from hyperlipidemic swine revealed that inducing diabetes
      with streptozotocin increased atherosclerotic lesion area and dramatically
      reduced the fraction of macrophages that expressed detectable ABCA1. These
      results raise the possibility that reactive carbonyl-mediated damage to ABCA1
      promotes accumulation of cholesterol in arterial macrophages and thus contribute
      to the increased cardiovascular disease associated with diabetes, insulin
      resistance, and other inflammatory conditions.

PMID- 15983223
TI  - Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction,
      and microalbuminuria of incipient diabetic nephropathy in patients.
AB  - Microalbuminuria, an early feature of diabetic nephropathy, indicates intrarenal
      endothelial damage. In type 2 diabetes, microalbuminuria is strongly related to
      insulin resistance. We therefore investigated whether rosiglitazone, an insulin
      sensitizing drug that is known to improve endothelial dysfunction, was able to
      improve intrarenal endothelial dysfunction and microalbuminuria. Nineteen type 2
      diabetic patients participated in this double-blind cross-over trial. Nine
      patients with newly diagnosed disease without microalbuminuria were randomized to
      a treatment with rosiglitazone or nateglinide, each for 12 weeks. Ten patients
      with microalbuminuria were randomized to rosiglitazone or placebo, each for 12
      weeks in addition to their previous antidiabetic medication. After each
      treatment, glomerular filtration rate (GFR), renal plasma flow, and filtration
      fraction were measured before and after blockade of nitric oxide (NO) by
      intravenous administration of N-monomethyl-L-arginine-acetate (L-NMMA). Ten
      healthy subjects served as control subjects. Type 2 diabetic patients at baseline
      showed glomerular hyperfiltration compared with healthy control subjects.
      Rosiglitazone reduced elevated GFR and filtration fraction toward control
      primarily in patients with microalbuminuria (GFR: 133.4 +/- 9.8 vs. 119.6 +/- 8.7
      ml/min; filtration fraction: 23.2 +/- 1.7 vs. 20.5 +/- 1.6% before and after
      rosiglitazone, respectively; control subjects: GFR 111.7 +/- 8.6 ml/min,
      filtration fraction 20.4 +/- 1.5%). Rosiglitazone improved intrarenal NO
      bioavailability in type 2 diabetes toward control as shown by infusion of L-NMMA.
      Rosiglitazone reduced albumin excretion in type 2 diabetes with microalbuminuria
      from 116.5 +/- 31 to 40.4 +/- 12 mg/day. Rosiglitazone ameliorated glomerular
      hyperfiltration in early type 2 diabetes, improved NO bioavailability, and
      lessened renal end-organ damage in type 2 diabetes with microalbuminuria.

PMID- 15983224
TI  - Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like
      peptide 1 and unmasks its insulinotropic effect in healthy subjects.
AB  - Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone
      due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1
      also decelerates gastric emptying, it physiologically reduces rather than
      augments postprandial insulin secretory responses. Therefore, we aimed to
      antagonize the deceleration of gastric emptying by GLP-1 to study its effects on
      insulin secretion after a meal. Nine healthy male volunteers (age 25 +/- 4 years,
      BMI 25.0 +/- 4.9 kg/m2) were studied with an infusion of GLP-1 (0.8 pmol.kg(
      1).min(-1) from -30 to 240 min) or placebo. On separate occasions, the prokinetic
      drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at -30
      min per oral), or erythromycin (200 mg intravenously from -30 to -15 min) were
      administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed
      amino acids in 400 ml) was administered at 0 min. Capillary and venous blood
      samples were drawn for the determination of glucose (glucose oxidase), insulin, C
      peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic
      polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol
      red dilution technique. Statistical analyses were performed using repeated
      measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the
      velocity of gastric emptying (P < 0.001). This was completely counterbalanced by
      erythromycin, whereas the other prokinetic drugs used had no effect. Postprandial
      glucose concentrations were lowered by GLP-1 (P < 0.001 vs. placebo), but this
      effect was partially reversed by erythromycin (P < 0.05). Insulin secretory
      responses to the meal were lower during GLP-1 administration (P < 0.05 vs.
      placebo). However, when erythromycin was added to GLP-1, insulin concentrations
      were similar to those in placebo experiments. The suppression of meal-related
      increments in glucagon secretion by GLP-1 was reversed by erythromycin (P <
      0.001). The time course of GIP secretion was delayed during GLP-1 administration
      (P < 0.05), but when erythromycin was added, the pattern was similar to placebo
      experiments. GLP-1 administration led to a reduction in pancreatic polypeptide
      plasma concentrations (P < 0.05). In contrast, pancreatic polypeptide levels were
      markedly increased by erythromycin (P < 0.001). Intravenous erythromycin
      counteracts the deceleration of gastric emptying caused by GLP-1, probably by
      interacting with the parasympathetic nervous system (pancreatic polypeptide
      responses). Despite augmented rises in insulin secretion, the glucose-lowering
      effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is
      antagonized, illustrating the importance of this facet of the multiple
      antidiabetic actions of GLP-1.

PMID- 15983225
TI  - Tempol reduces oxidative stress, improves insulin sensitivity, decreases renal
      dopamine D1 receptor hyperphosphorylation, and restores D1 receptor-G-protein
      coupling and function in obese Zucker rats.
AB  - Oxidative stress plays a pathogenic role in hypertension, particularly the one
      associated with diabetes and obesity. Here, we test the hypothesis that renal
      dopamine D1 receptor dysfunction in obese Zucker rats is caused by oxidative
      stress. One group each from lean and obese Zucker rats received tempol, a
      superoxide dismutase mimetic in drinking water for 2 weeks. Obese animals were
      hypertensive, hyperglycemic, and hyperinsulinemic, exhibited renal oxidative
      stress, and increased protein kinase C activity. Also, there was
      hyperphosphorylation of D1 receptor, defective receptor-G-protein coupling,
      blunted dopamine-induced Na+-K+-ATPase inhibition, and diminished natriuretic
      response to D1 receptor agonist, SKF-38393. However, obese animals had elevated
      levels of plasma nitric oxide and urinary cGMP. In addition, L-N-nitroarginine
      and sodium nitroprusside showed similar effect on blood pressure in lean and
      obese rats. In obese animals, tempol reduced blood pressure, blood glucose,
      insulin, renal oxidative stress, and protein kinase C activity. Tempol also
      decreased D1 receptor phosphorylation and restored receptor G-protein coupling.
      Dopamine inhibited Na+-K+-ATPase activity, and SKF-38393 elicited a natriuretic
      response in tempol-treated obese rats. Thus in obese Zucker rats, tempol
      ameliorates oxidative stress and improves insulin sensitivity. Consequently,
      hyperphosphorylation of D1 receptor is reduced, leading to restoration of
      receptor-G-protein coupling and the natriuretic response to SKF-38393.

PMID- 15983226
TI  - Signaling pathways involved in human vascular smooth muscle cell proliferation
      and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of
      metformin.
AB  - Accumulating evidence suggests that high concentrations of leptin observed in
      obesity and diabetes may contribute to their adverse effects on cardiovascular
      health. Metformin monotherapy is associated with reduced macrovascular
      complications in overweight patients with type 2 diabetes. It is uncertain
      whether such improvement in the cardiovascular outcome is related to specific
      vasculoprotective effects of this drug. In the present study, we determined the
      effect of leptin on human aortic smooth muscle cell (HASMC) proliferation and
      matrix metalloproteinase (MMP)-2 expression, the signaling pathways mediating
      these effects, and the modulatory effect of metformin on these parameters.
      Incubation of HASMCs with leptin enhanced the proliferation and MMP-2 expression
      in these cells and increased the generation of intracellular reactive oxygen
      species (ROS). These effects were abolished by vitamin E. Inhibition of NAD(P)H
      oxidase and protein kinase C (PKC) suppressed the effect of leptin on ROS
      production. In HASMCs, leptin induced PKC, extracellular signal-regulated kinase
      (ERK)1/2, and nuclear factor-kappaB (NF-kappaB) activation and inhibition of
      these signaling pathways abrogated HASMC proliferation and MMP-2 expression
      induced by this hormone. Treatment of HASMCs with metformin decreased leptin
      induced ROS production and activation of PKC, ERK1/2, and NF-kappaB. Metformin
      also inhibited the effect of leptin on HASMC proliferation and MMP-2 expression.
      Overall, these results demonstrate that leptin induced HASMC proliferation and
      MMP-2 expression through a PKC-dependent activation of NAD(P)H oxidase with
      subsequent activation of the ERK1/2/NF-kappaB pathways and that therapeutic
      metformin concentrations effectively inhibit these biological effects. These
      results suggest a new mechanism by which metformin may improve cardiovascular
      outcome in patients with diabetes.

PMID- 15983227
TI  - Long-term treatment with rosiglitazone and metformin reduces the extent of, but
      does not prevent, islet amyloid deposition in mice expressing the gene for human
      islet amyloid polypeptide.
AB  - Islet amyloid deposition in type 2 diabetes is associated with reduced beta-cell
      mass. Therefore, interventions aimed at reducing islet amyloid formation may help
      preserve beta-cell mass in type 2 diabetes. Rosiglitazone and metformin act by
      different mechanisms to improve insulin sensitivity and thereby reduce beta-cell
      secretory demand, resulting in decreased release of insulin and islet amyloid
      polypeptide (IAPP), the unique constituent of islet amyloid deposits. We
      hypothesized that this reduced beta-cell secretory demand would lead to reduced
      islet amyloid formation. Human IAPP (hIAPP) transgenic mice, a model of islet
      amyloid, were treated for 12 months with rosiglitazone (1.5 mg.kg(-1).day(-1), n
      = 19), metformin (1 g.kg(-1).day(-1), n = 18), or control (n = 17). At the end of
      the study, islet amyloid prevalence (percent islets containing amyloid) and
      severity (percent islet area occupied by amyloid), islet mass, beta-cell mass,
      and insulin release were determined. Islet amyloid prevalence (44 +/- 8, 13 +/-
      4, and 11 +/- 3% for control, metformin-, and rosiglitazone-treated mice,
      respectively) and severity (9.2 +/- 3.0, 0.22 +/- 0.11, and 0.10 +/- 0.05% for
      control, metformin-, and rosiglitazone-treated mice, respectively) were markedly
      reduced with both rosiglitazone (P < 0.001 for both measures) and metformin
      treatment (P < 0.001 for both measures). Both treatments were associated with
      reduced insulin release assessed as the acute insulin response to intravenous
      glucose (2,189 +/- 857, 621 +/- 256, and 14 +/- 158 pmol/l for control, metformin
      , and rosiglitazone-treated mice, respectively; P < 0.05 for metformin vs.
      control and P < 0.005 for rosiglitazone vs. control), consistent with reduced
      secretory demand. Similarly, islet mass (33.4 +/- 7.0, 16.6 +/- 3.6, and 12.2 +/-
      2.1 mg for control, metformin-, and rosiglitazone-treated mice, respectively) was
      not different with metformin treatment (P = 0.06 vs. control) but was
      significantly lower with rosiglitazone treatment (P < 0.05 vs. control). When the
      decreased islet mass was accounted for, the islet amyloid-related decrease in
      beta-cell mass (percent beta-cell mass/islet mass) was ameliorated in both
      rosiglitazone- and metformin-treated animals (57.9 +/- 3.1, 64.7 +/- 1.4, and
      66.1 +/- 1.6% for control, metformin-, and rosiglitazone-treated mice,
      respectively; P < 0.05 for metformin or rosiglitazone vs. control). In summary,
      rosiglitazone and metformin protect beta-cells from the deleterious effects of
      islet amyloid, and this effect may contribute to the ability of these treatments
      to alleviate the progressive loss of beta-cell mass and function in type 2
      diabetes.

PMID- 15983228
TI  - Genetic variation in adiponectin receptor 1 and adiponectin receptor 2 is
      associated with type 2 diabetes in the Old Order Amish.
AB  - Adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) are newly
      identified receptors for adiponectin, an adipocytokine with anti-inflammatory and
      insulin-sensitizing properties. We screened for polymorphisms by performing
      sequence analysis on all eight exons, splice junctions, and approximately 2 kb of
      the 5' flanking regions of each receptor. We detected 5 single nucleotide
      polymorphisms (SNPs) in ADIPOR1 and 16 SNPs in ADIPOR2. We genotyped these SNPs
      in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance
      (IGT) (n = 139), and normal glucose tolerance (n = 342) to test for association
      with type 2 diabetes. Three intronic SNPs in ADIPOR1 were significantly
      associated with type 2 diabetes (P = 0.014-0.007; odds ratio [OR] 1.61-1.65) and
      in high linkage disequilibrium (r2 = 0.97-1.0). In ADIPOR2, we found that five
      SNPs delineated one large haplotype block (r2= 0.9-1.0) spanning >98 kb of the
      gene and promoter region, which was strongly associated with the combined type 2
      diabetes/IGT trait (P < or = 0.001; OR 1.64-1.71). To our knowledge, these data
      provide the first evidence for association between variation in the adiponectin
      receptors and type 2 diabetes.

PMID- 15983229
TI  - Hepatic lipase gene variant -514C>T is associated with lipoprotein and insulin
      sensitivity response to regular exercise: the HERITAGE Family Study.
AB  - We investigated the associations between the hepatic lipase gene (LIPC) -514C>T
      polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to
      exercise training. Hepatic lipase and lipoprotein lipase activities, plasma
      lipoprotein levels, and Si were measured in the sedentary state and post-exercise
      training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE)
      Family Study (n=662). The LIPC -514C allele frequency was 0.516 (blacks) and
      0.796 (whites). Baseline and post-exercise training hepatic lipase activities
      were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC
      homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol,
      HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower
      baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained
      low post-exercise training. Baseline Si was not associated with the LIPC
      genotypes. However, training-induced improvements in Si both in blacks and whites
      were greater in CC homozygotes (+1.25 +/- 0.2 and +0.22 +/- 0.2 microU.min(
      1).ml(-1)) than in the TT genotype (+0.27 +/- 0.3 and -0.97 +/- 0.3 microU.min(
      1).ml(-1)) (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was
      associated with higher hepatic lipase activity in sedentary and physically active
      states and better Si responses to regular exercise both in black and white
      individuals. The benefits from an exercise program on Si are likely to be
      substantial in the general population given the high frequency of the LIPC -514C
      allele, particularly in whites.

PMID- 15983230
TI  - Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from
      impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention
      Study.
AB  - Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of
      this study was to investigate whether single nucleotide polymorphisms (SNPs) in
      the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1
      [encoding HNF-1alpha], HNF4A, GIP, and GLP1R) are associated with the conversion
      from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the
      Finnish Diabetes Prevention Study. With the exception of SLC2A2, other genes were
      not associated with the risk of type 2 diabetes. All four SNPs of SLC2A2
      predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk
      of type 2 diabetes in the entire study population by threefold (odds ratio 3.04,
      95% CI 1.34-6.88, P = 0.008). The risk for type 2 diabetes in the AA genotype
      carriers was increased in the control group (5.56 [1.78-17.39], P = 0.003) but
      not in the intervention group. We conclude that the SNPs of SLC2A2 predict the
      conversion to diabetes in obese subjects with IGT.

PMID- 15983231
TI  - Evidence of an association between the Arg72 allele of the peptide YY and
      increased risk of type 2 diabetes.
AB  - We tested the hypothesis that variants in the gene encoding the prepropeptide YY
      (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA
      from 84 patients with obesity and familial type 2 diabetes identified two
      polymorphisms, IVS3 + 68C>T and Arg72Thr, and one rare variant, +151C>A of PYY.
      The common allele of the Arg72Thr variant associated with type 2 diabetes with an
      allele frequency of the Arg allele of 0.667 (95% CI 0.658-0.677) among 4,639
      glucose-tolerant subjects and 0.692 (0.674-0.710) among 1,326 patients with type
      2 diabetes (P = 0.005, odds ratio 1.19 [95% CI 1.05-1.35]). The same polymorphism
      associated with overweight (25 < or = BMI < 30 kg/m2) (P = 0.018, 1.15 [1.02
      1.28]). In quantitative trait analyses of a population-based sample of 6,022
      subjects, the Arg allele was associated with an increased plasma glucose level 2
      h after an oral glucose tolerance test (OGTT) (P = 0.03), an increased area under
      the curve for the post-OGTT plasma glucose level (P = 0.03), and a lower
      insulinogenic index (P = 0.01). In conclusion, the common Arg allele of the PYY
      Arg72Thr variant modestly associates with type 2 diabetes and with type 2
      diabetes-related quantitative traits.

PMID- 15983232
TI  - Delayed transcapillary delivery of insulin to muscle interstitial fluid after
      oral glucose load in obese subjects.

PMID- 15983234
TI  - Obstructive sleep apnea-dependent and -independent adrenergic activation in
      obesity.
AB  - No agreement exists as to the mechanisms responsible for the sympathetic
      hyperactivity characterizing human obesity, which has been ascribed recently to a
      chemoreflex stimulation brought about by obstructive sleep apnea rather than to
      an increase in body weight, per se. In 86 middle-age normotensive subjects
      classified according to body mass index, waist-to-hip ratio, and apnea/hypopnea
      index (overnight polysomnographic evaluation) as lean and obese subjects without
      or with obstructive sleep apnea, we assessed via microneurography muscle
      sympathetic nerve traffic. The 4 groups were matched for age, gender, and blood
      pressure values, the 2 obese groups with and without obstructive sleep apnea
      showing a similar increase in body mass index (32.4 versus 32.0 kg/m2,
      respectively) and waist-to-hip ratio (0.96 versus 0.95, respectively) compared
      with the 2 lean groups with or without obstructive sleep apnea (body mass index
      24.3 versus 23.8 kg/m2 and waist-to-hip ratio 0.77 versus 0.76, respectively;
      P<0.01). Compared with the nonobstructive sleep apnea lean group, muscle
      sympathetic nerve activity showed a similar increase in the obstructive sleep
      apnea lean group and in the nonobstructive sleep apnea obese group (60.4+/-2.3
      and 59.3+/-2.0 versus 40.9+/-1.8 bs/100 hb, respectively; P<0.01), a further
      increase being detected in obstructive sleep apnea subjects (73.1+/-2.5
      bursts/100 heart beats; P<0.01). Our data demonstrate that the sympathetic
      activation of obesity occurs independently in obstructive sleep apnea. They also
      show that this condition exerts sympathostimulating effects independent of body
      weight, and that the obstructive sleep apnea-dependent and -independent
      sympathostimulation contribute to the overall adrenergic activation of the obese
      state.

PMID- 15983235
TI  - Blood pressure in adulthood and life expectancy with cardiovascular disease in
      men and women: life course analysis.
AB  - Limited information exists about the consequences of hypertension during
      adulthood on residual life expectancy with cardiovascular disease. We aimed to
      analyze the life course of people with high blood pressure levels at age 50 in
      terms of total life expectancy and life expectancy with and without
      cardiovascular disease compared with normotensives. We constructed multistate
      life tables for cardiovascular disease, myocardial infarction, and stroke using
      data from 3128 participants of the Framingham Heart Study who had their 50th
      birthday while enrolled in the study. For the life table calculations, we used
      hazard ratios for 3 transitions (healthy to death, healthy to disease, and
      disease to death) by categories of blood pressure level and adjusted by age, sex,
      and confounders. Irrespective of sex, 50-year-old hypertensives compared with
      normotensives had a shorter life expectancy, a shorter life expectancy free of
      cardiovascular disease, myocardial infarction, and stroke, and a longer life
      expectancy lived with these diseases. Normotensive men (22% of men) survived 7.2
      years (95% confidence interval, 5.6 to 9.0) longer without cardiovascular disease
      compared with hypertensives and spent 2.1 (0.9 to 3.4) fewer years of life with
      cardiovascular disease. Similar differences were observed in women. Compared with
      hypertensives, total life expectancy was 5.1 and 4.9 years longer for
      normotensive men and women, respectively. Increased blood pressure in adulthood
      is associated with large reductions in life expectancy and more years lived with
      cardiovascular disease. This effect is larger than estimated previously and
      affects both sexes similarly. Our findings underline the tremendous importance of
      preventing high blood pressure and its consequences in the population.

PMID- 15983236
TI  - Does blood pressure control contribute to a more successful aging?

PMID- 15983237
TI  - Parental longevity and 7-year changes in blood pressures in adult offspring.
AB  - In this report, we examined the cross-sectional and the 7-year longitudinal
      changes in blood pressures in adult offspring according to parental longevity. A
      population of volunteers free of symptomatic cardiovascular diseases who
      participated to the Supplementation en Vitamines et en Mineraux Antioxydants
      (SUVIMAX) Vascular Study (mean age 52.3 years; 48.3% women) were examined at
      baseline and 7 years later. Paternal (n=994) and maternal (n=896) longevity were
      analyzed separately. The prevalence of hypertension at baseline in subjects whose
      father died at <65 years of age, in those whose fathers were alive by age 65 but
      died by 80 years of age, and in those whose fathers were alive by age 80 was
      respectively 34.9%, 28.5%, and 20.2% (P<0.001). The means of systolic blood
      pressure in the 3 groups of paternal longevity were respectively 128.4 (+/-16.0),
      125.3 (+/-14.2), and 123.6 (+/-14.4) mm Hg (P<0.001). During the follow-up, the
      mean systolic blood pressure increases in the 3 groups of paternal longevity were
      respectively 5.3 (+/-17.0), 4.2 (+/-14.0), and 1.6 (+/-13.2) mm Hg (P<0.001). In
      subjects without hypertension at baseline, hypertension occurred during the
      follow-up in 26.6%, 17.7%, and 15.3% (P<0.009), respectively. Multivariate
      analyses adjusted for baseline or changes in cardiovascular risk factors did not
      modify these results. In contrast, there was no relationship between maternal
      longevity and blood pressure measurements in either cross-sectional or
      longitudinal analyses. This study suggests that paternal premature death was
      associated with accelerated progression of systolic blood pressure and higher
      occurrence of hypertension in offspring. These results indicate that there are
      dynamic and continuous processes linking paternal longevity to blood pressure in
      adults.

PMID- 15983239
TI  - Effects of noncardiovascular comorbidities on antihypertensive use in elderly
      hypertensives.
AB  - Although the benefits of antihypertensive drugs have been clearly established,
      they remain underused by vulnerable older populations. We examined whether the
      presence of noncardiovascular comorbidity deters use of antihypertensives in
      elderly with hypertension. We conducted a retrospective cohort study among 51,517
      patients > or =65 years of age in the Pennsylvania Pharmaceutical Assistance
      Contract for the Elderly (PACE) Program during 1999 and 2000. All were
      hypertensive and had diagnoses and used treatments during 1999 to qualify for
      entry into 1 of the following 5 mutually exclusive cohorts: asthma/chronic
      obstructive pulmonary disease (COPD), depression, gastrointestinal (GI)
      disorders, osteoarthritis, or none of the 4 comorbidities. Proportions using
      antihypertensives in 2000 were assessed. Logistic regression analysis was used to
      identify the independent effects on antihypertensive use of the 4 comorbidities
      of interest, sociodemographic characteristics, other cardiovascular and
      noncardiovascular comorbidity, and health care utilization variables. After
      adjustments in multivariable analyses, antihypertensive use was consistently
      lower in patients with asthma/COPD (odds ratio [OR], 0.43; 95% confidence
      interval [CI], 0.40 to 0.47), depression (OR, 0.50; 95% CI, 0.45 to 0.55), GI
      disorders (OR, 0.59; 95% CI, 0.54 to 0.64), and osteoarthritis (OR, 0.63; 95% CI,
      0.59 to 0.67) relative to those without these conditions. Reduced
      antihypertensive use was also associated with older age, female gender, white
      race, more severe other comorbidities, absence of some cardiovascular
      indications, hospitalizations, nursing home care, physician visits, and use of
      fewer other medications. Highly prevalent, noncardiovascular conditions appear to
      deter use of antihypertensives in elderly with hypertension.

PMID- 15983238
TI  - Sex hormones as potential modulators of vascular function in hypertension.
AB  - The greater incidence of hypertension in men and postmenopausal women compared
      with premenopausal women has suggested gender differences in vascular function.
      Vascular effects of the female sex hormones estrogen and progesterone and the
      male hormone testosterone have been described. Sex steroid receptors have been
      identified in vascular endothelium and smooth muscle. Interaction of sex hormones
      with cytosolic/nuclear receptors initiates long-term genomic effects that
      stimulate endothelial cell growth but inhibit smooth muscle proliferation.
      Activation of sex hormone receptors on the plasma membrane triggers nongenomic
      effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP,
      prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause
      endothelium-independent inhibition of vascular smooth muscle contraction,
      [Ca2+]i, and protein kinase C. These vasorelaxant/vasodilator effects suggested
      vascular benefits of hormone replacement therapy (HRT) during natural and
      surgically induced deficiencies of gonadal hormones. Although some clinical
      trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of
      effect should not be generalized because it could be related to the type/dose of
      sex hormone, subjects' age, and other cardiovascular conditions. The prospect of
      HRT relies on continued investigation of the molecular mechanisms underlying the
      vascular effects of sex hormones and identification of compounds that
      specifically target the vascular sex hormone receptors. Naturally occurring
      hormones and phytoestrogens may be more beneficial HRT than synthesized
      compounds. Also, the type/dose, time of initiation, and duration of HRT should be
      customized depending on the subject's age and preexisting cardiovascular
      condition, and thereby enhance the outlook of sex hormones as potential
      modulators of vascular function in hypertension.

PMID- 15983240
TI  - Modest salt reduction reduces blood pressure and urine protein excretion in black
      hypertensives: a randomized control trial.
AB  - High blood pressure and proteinuria are the major risk factors for cardiovascular
      and renal disease. In black individuals, there is an increased risk of
      hypertension, stroke, heart failure, and kidney disease. There are no controlled
      studies of the effects of reducing salt intake on blood pressure and urine
      protein excretion in black individuals. Therefore, the aim of our study was to
      determine the effects of modest salt restriction on blood pressure and urine
      protein excretion in nondiabetic black hypertensive subjects. The study was
      randomized, double blind, and placebo controlled. After run-in periods on their
      usual diet and on reduced salt, participants continued to restrict their salt
      intake and then received either slow sodium tablets, designed to bring their salt
      intake back to normal, or placebo tablets for 4 weeks in a randomized, double
      blind, crossover study. In the 40 who completed the study, urinary sodium
      excretion fell on slow sodium to placebo from 169+/-73 to 89+/-52 mmol per 24
      hours (P<0.001; approximately 10 to 5 g salt per day). Blood pressure fell from
      159/101+/-13/8 to 151/98+/-13/8 mm Hg (P<0.01). Protein excretion fell from 93+/
      48 mg to 75+/-30 mg per 24 hours (P<0.008). Thus, reducing salt intake from
      approximately 10 to 5 g per day reduced blood pressure and urine protein
      excretion in black hypertensives. In light of these findings, we would recommend
      that all black individuals with raised blood pressure reduce their salt intake to
      < or =5 g per day.

PMID- 15983241
TI  - Bcl-xL gene transfer inhibits Bax translocation and prolongs cardiac cold
      preservation time in rats.
AB  - BACKGROUND: Apoptosis is an important cause of early graft loss after heart
      transplantation. Bcl-xL was reported to protect the heart against normothermic
      ischemia and reperfusion injury. In this study, we determined whether
      overexpression of Bcl-xL could inhibit tissue injury resulting from prolonged
      cold preservation followed by warm reperfusion of heart transplants. METHODS AND
      RESULTS: Lewis rat hearts were transduced with an adenovirus vector harboring Bcl
      xL cDNA (AxCAhBclxL) 4 days before collection of tissue. After preservation in
      University of Wisconsin solution at 4 degrees C for 24 hours, the heart was
      either perfused with a Langendorff device ex vivo or used for heterotopic heart
      transplantation in vivo. Bcl-xL gene transfer significantly reduced the infarct
      size (23.0+/-2.6% versus 47.7+/-7.0% in saline control and 48.6+/-6.1% in vector
      control, P<0.01) after 2-hour reperfusion at 37 degrees C with the Langendorff
      device and significantly decreased creatine kinase release (0.82+/-0.27 IU,
      versus 1.57+/-0.33 and 1.50+/-0.37 IU in saline and vector controls,
      respectively; P<0.05). In heart transplantation, overexpression of Bcl-xL
      inhibited Bax translocation from the cytosol to the mitochondria, resulting in
      decreased cytochrome c release from the mitochondria; it also significantly
      decreased cardiac cell apoptosis and improved graft survival rate after long cold
      preservation, followed by warm reperfusion. CONCLUSIONS: Bcl-xL gene transfer
      inhibited the translocation of Bax and prolonged the cold preservation time of
      cardiac transplants. This may be a potential therapeutic method in clinical
      practice.

PMID- 15983242
TI  - Effects of candesartan on the development of a new diagnosis of diabetes mellitus
      in patients with heart failure.
AB  - BACKGROUND: Diabetes is a risk factor for heart failure, and both conditions are
      increasing. Identifying treatments that prevent both conditions will be
      clinically important. We previously reported that candesartan (an angiotensin
      receptor blocker) reduces cardiovascular mortality and heart failure
      hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure
      Assessment of Reduction in Mortality and Morbidity Program). METHODS AND RESULTS:
      We assessed the impact of candesartan versus placebo on the development of
      diabetes, a predefined secondary outcome in a randomized, controlled, double
      blind study involving 5436 of the 7601 patients with heart failure, irrespective
      of ejection fraction, who did not have a diagnosis of diabetes at entry into the
      trial. Patients received candesartan (target of 32 mg once daily) or matching
      placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the
      candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo
      group (hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to
      0.96; P=0.020). The composite end point of death or diabetes occurred in 692
      (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR,
      0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically
      heterogeneous in the various subgroups examined, although the apparent magnitude
      of benefit appeared to be smaller among those treated concomitantly with
      angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65
      to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to
      0.93; P for heterogeneity, 0.28). CONCLUSIONS: The angiotensin receptor blocker
      candesartan appears to prevent diabetes in heart failure patients, suggesting
      that the renin-angiotensin axis is implicated in glucose regulation.

PMID- 15983243
TI  - Adoption of spironolactone therapy for older patients with heart failure and left
      ventricular systolic dysfunction in the United States, 1998-2001.
AB  - BACKGROUND: Concerns have been raised about the appropriateness of spironolactone
      use in some patients with heart failure. We studied the adoption of
      spironolactone therapy after publication of the Randomized Aldactone Evaluation
      Study (RALES) in national cohorts of older patients hospitalized for heart
      failure. METHODS AND RESULTS: This is a study of serial cross-sectional samples
      of Medicare beneficiaries > or =65 years old discharged after hospitalization for
      the primary diagnosis of heart failure and with left ventricular systolic
      dysfunction. The first sample was discharged before (April 1998 to March 1999,
      n=9758) and the second sample after (July 2000 to June 2001, n=9468) publication
      of RALES in September 1999. We assessed spironolactone prescriptions at hospital
      discharge in patient groups defined by enrollment criteria for the trial. Using
      multivariable logistic regression, we identified factors independently associated
      with prescriptions not meeting these criteria. Spironolactone use increased >7
      fold (3.0% to 21.3% P<0.0001) after RALES. Of patients meeting enrollment
      criteria, 24.1% received spironolactone, as compared with 17.4% of those not
      meeting the criteria. Of all prescriptions after RALES, 30.9% were provided to
      patients not meeting enrollment criteria. Spironolactone was prescribed to 22.8%
      of patients with a serum potassium value > or =5.0 mmol/L, to 14.1% with a serum
      creatinine value > or =2.5 mg/dL, and to 17.3% with severe renal dysfunction
      (estimated glomerular filtration rate <30 mL.min(-1).1.73 m(-2)). In
      multivariable analyses, factors associated with prescriptions not meeting
      enrollment criteria included advanced age, noncardiovascular comorbidities,
      discharge to skilled nursing facilities, and care provided by physicians without
      board certification. CONCLUSIONS: Spironolactone prescriptions increased markedly
      after the publication of RALES, and many treated patients were at risk for
      hyperkalemia. Simultaneously, many patients who might have benefited were not
      treated. These findings demonstrate the importance of balancing efforts to
      enhance use among appropriate patients and minimizing use in patients at risk for
      adverse events.

PMID- 15983244
TI  - Augmented cardiac hypertrophy in response to pressure overload in mice lacking
      the prostaglandin I2 receptor.
AB  - BACKGROUND: In the heart, the expressions of several types of prostanoid
      receptors have been reported. However, their roles in cardiac hypertrophy in vivo
      remain unknown. We intended to clarify the roles of these receptors in pressure
      overload-induced cardiac hypertrophy using mice lacking each of their receptors.
      METHODS AND RESULTS: We used a model of pressure overload-induced cardiac
      hypertrophy produced by banding of the transverse aorta in female mice. In wild
      type mice subjected to the banding, cardiac hypertrophy developed during the
      observation period of 8 weeks. In mice lacking the prostaglandin (PG) I2 receptor
      (IP(-/-)), however, cardiac hypertrophy and cardiomyocyte hypertrophy were
      significantly greater than in wild-type mice at 2 and 4 weeks but not at 8 weeks,
      whereas there was no such augmentation in mice lacking the prostanoid receptors
      other than IP. In addition, cardiac fibrosis observed in wild-type hearts was
      augmented in IP(-/-) hearts, which persisted for up to 8 weeks. In IP(-/-)
      hearts, the expression level of mRNA for atrial natriuretic peptide, a
      representative marker of cardiac hypertrophy, was significantly higher than in
      wild-type hearts. In vitro, cicaprost, an IP agonist, reduced platelet-derived
      growth factor-induced proliferation of wild-type noncardiomyocytes, although it
      could not inhibit cardiotrophin-1-induced hypertrophy of cardiomyocytes.
      Accordingly, cicaprost increased cAMP concentration efficiently in
      noncardiomyocytes. CONCLUSIONS: IP plays a suppressive role in the development of
      pressure overload-induced cardiac hypertrophy via the inhibition of both
      cardiomyocyte hypertrophy and cardiac fibrosis. Both effects have been suggested
      as originating from the action on noncardiomyocytes rather than cardiomyocytes.

PMID- 15983245
TI  - Prediction of myocardial infarction by N-terminal-pro-B-type natriuretic peptide,
      C-reactive protein, and renin in subjects with cerebrovascular disease.
AB  - BACKGROUND: B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin
      are elevated in persons at risk for cardiovascular disease. However, data that
      directly compare these markers in the prediction of myocardial infarction (MI)
      are limited. METHODS AND RESULTS: N-terminal-proBNP (NT-proBNP), CRP, and renin
      were measured in baseline blood samples from a nested case-control study of the
      6105 participants of the Perindopril Protection Against Recurrent Stroke Study
      (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure
      lowering regimen among individuals with previous stroke or transient ischemic
      attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during
      a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI
      cases (67%) occurred in subjects without a history of coronary heart disease. NT
      proBNP, CRP, and renin each predicted MI; the odds ratio for subjects in the
      highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6) for NT
      proBNP, 2.2 (95% CI, 1.3 to 3.6) for CRP, and 1.7 (95% CI, 1.1 to 2.8) for renin.
      NT-proBNP and renin, but not CRP, remained predictors of MI after adjustment for
      all other predictors, including LDL and HDL cholesterol levels. Individuals with
      both NT-proBNP and renin in their highest quarters had 4.5 times the risk of MI
      compared with subjects with both biological markers in their lowest quarters.
      CONCLUSIONS: NT-proBNP and renin, but not CRP, are independent predictors of MI
      risk after stroke or transient ischemic attack, providing information additional
      to that provided by classic risk factors, and may enable more effective targeting
      of MI prevention strategies.

PMID- 15983246
TI  - Obesity, insulin resistance, and the metabolic syndrome: determinants of
      endothelial dysfunction in whites and blacks.
AB  - BACKGROUND: Insulin resistance is strongly associated with obesity and other
      components of the metabolic syndrome (MS). The relative importance of these
      components in the determination of endothelial function is unknown. Furthermore,
      there is conflicting evidence about whether ethnic differences exist in the
      relative importance of these components in regard to other cardiovascular
      outcomes. We evaluated the contributions of insulin resistance, obesity, and the
      other components of the MS to impaired endothelial function. METHODS AND RESULTS:
      The relationships of the MS components (as defined according the National
      Cholesterol Education Program) and insulin resistance (estimated using the
      homeostasis model) with endothelium-dependent vasodilation were examined in 42
      white and 55 black subjects. Endothelium-dependent vasodilation was assessed as
      the increment in leg blood flow (measured by thermodilution) after exposure to
      methacholine chloride. Waist circumference, glucose, blood pressure, and insulin
      resistance distributions did not differ between ethnic groups; blacks in our
      sample had higher HDL cholesterol (1.31 versus 1.09 mmol/L; P<0.001) and lower
      triglyceride levels (1.01 versus 1.37 mmol/L; P=0.005) than white subjects. In
      the absence of the MS, black subjects exhibited reduced endothelium-dependent
      vasodilation compared with white subjects (P=0.005), and both groups demonstrated
      significantly worse endothelial function when the MS was present (maximal
      increase in leg blood flow: blacks: 107+/-9% MS absent, 53+/-16% MS present;
      whites: 163+/-16% MS absent, 54+/-18% MS absent; P=0.007, MS absent versus
      present; P=NS for interaction of ethnicity and MS). Multivariable regression
      analysis examining relationships of endothelial function with the 5 MS components
      (analyzed as continuous variables) revealed independent relationships only with
      waist circumference (P=0.01) and systolic blood pressure (P=0.02). Waist
      circumference was no longer independently associated after adding insulin
      resistance to the modeling (P=0.02 for log of homeostasis model index of insulin
      resistance, P=0.02 for systolic blood pressure). Ethnicity still exerted an
      independent effect on endothelial function after accounting for the above
      components (P=0.04 for an additional effect of ethnic status on endothelial
      function), with an ethnic difference in the effect of insulin resistance on
      endothelial function (P=0.046 for interaction of ethnicity and log of homeostasis
      model index of insulin resistance). CONCLUSIONS: These findings suggest that
      insulin resistance and systolic blood pressure are the principal determinants of
      endothelial dysfunction in the MS and that there are ethnic differences in the
      relative importance of these factors. These differences may imply different
      benefits from treatments targeting blood pressure or insulin resistance in
      different ethnic groups.

PMID- 15983247
TI  - Early structural and functional changes of the vasculature in HIV-infected
      children: impact of disease and antiretroviral therapy.
AB  - BACKGROUND: Premature cardiovascular disease is increasingly recognized in HIV
      infected patients, but the mechanisms involved are unclear. The purpose of this
      study was to determine the impact of HIV infection and antiretroviral therapy
      (ART) on markers of early vascular disease in children. METHODS AND RESULTS: We
      studied 83 HIV-infected children (56 had taken ART, of whom 31 received a regimen
      containing protease inhibitors [PIs]; 27 were never treated) and a control group
      of 59 healthy children. Carotid intima-media thickness (IMT) and brachial artery
      flow-mediated dilatation (FMD) were measured. IMT was significantly greater in
      HIV-infected children compared with the control subjects (P<0.001). Among the HIV
      infected children, age and treatment were significantly associated with increased
      IMT. Children exposed to PIs had greater IMT compared with both non-PI-treated
      children and untreated children (P=0.02). FMD was also significantly reduced in
      the HIV-infected children compared with control subjects (P=0.02). Pairwise
      comparisons of different treatment exposure groups revealed that FMD was impaired
      by a mean of 3.6% (95% CI, 1.8 to 5.3; P<0.001) for children exposed to PIs
      compared with untreated children and by a mean of 1.8% (95% CI, 0.01 to 3.5;
      P=0.05) compared with non-PI-treated children. HIV-infected children had lipid
      abnormalities, but they did not account for the observed differences in either
      FMD or IMT. CONCLUSIONS: HIV infection in childhood is associated with adverse
      structural and functional vascular changes that are most pronounced in children
      exposed to PI therapy. Longitudinal studies are required to differentiate the
      relative impact of HIV disease and ART and to assess the potential for
      prevention.

PMID- 15983248
TI  - Periodontal disease and coronary heart disease: a reappraisal of the exposure.
AB  - BACKGROUND: Results from studies relating periodontal disease to cardiovascular
      disease have been mixed. Residual confounding by smoking and use of clinical
      measures of periodontal disease rather than measures of infection have been 2
      major criticisms. The aims of this study were to investigate relationships
      between prevalent coronary heart disease (CHD) and 2 exposures, (1) clinical
      periodontal disease and (2) IgG antibodies to 17 oral organisms, and to evaluate
      the role of smoking in these relationships. METHODS AND RESULTS: Our study is
      based on a subset of participants in the Atherosclerosis Risk in Communities
      (ARIC) Study, who received a complete periodontal examination during visit 4
      (1996-1998). The exposures were periodontal status and serum IgG antibody levels
      against 17 periodontal organisms, and the outcome was prevalent CHD at visit 4.
      Multivariable analyses indicate that periodontal status is not significantly
      associated with CHD in either ever smokers or never smokers. Similar analyses
      evaluating antibodies indicate that high antibodies (above the median) to
      Treponema denticola (odds ratio [OR]=1.7; 95% CI, 1.2 to 2.3), Prevotella
      intermedia (OR=1.5; 95% CI, 1.1 to 2.0), Capnocytophaga ochracea (OR=1.5; 95% CI,
      1.1 to 2.1), and Veillonella parvula (OR=1.7; 95% CI, 1.2 to 2.3) are
      significantly associated with CHD among ever smokers, whereas Prevotella
      nigrescens (OR=1.7; 95% CI, 1.1 to 2.6), Actinobacillus actinomycetemcomitans
      (OR=1.7; 95% CI, 1.2 to 2.7), and Capnocytophaga ochracea (OR=2.0; 95% CI, 1.3 to
      3.0) were associated with CHD among never smokers. CONCLUSIONS: Clinical signs of
      periodontal disease were not associated with CHD, whereas systemic antibody
      response was associated with CHD in ever smokers and never smokers. These
      findings indicate that the quality and quantity of the host response to oral
      bacteria may be an exposure more relevant to systemic atherothrombotic coronary
      events than clinical measures.

PMID- 15983249
TI  - Neuronal nitric oxide synthase mediates statin-induced restoration of vasa
      nervorum and reversal of diabetic neuropathy.
AB  - BACKGROUND: Peripheral neuropathy is a frequent and major complication of
      diabetes. METHODS AND RESULTS: Severe peripheral neuropathy developed in type II
      diabetic mice, characterized by significant slowing of motor and sensory nerve
      conduction velocities. Rosuvastatin restored nerve vascularity, including vessel
      size, and nerve function also recovered to the levels of nondiabetic mice.
      Neuronal nitric oxide synthase expression in sciatic nerves was reduced in
      diabetic mice but was preserved by rosuvastatin. Coadministration of a nitric
      oxide synthase inhibitor with rosuvastatin attenuated the beneficial effects of
      rosuvastatin on nerve function and limited the recovery of vasa nervorum and
      nerve function. In vitro, rosuvastatin inhibited downregulation of neuronal
      nitric oxide synthase expression induced by high-glucose conditions in cultured
      Schwann cells. Furthermore, Akt phosphorylation in Schwann cells, downregulated
      by high-glucose conditions, was also restored by rosuvastatin, consistent with
      the change of neuronal nitric oxide synthase expression. Akt inhibition
      independently reduced neuronal nitric oxide synthase expression in Schwann cells
      in low-glucose cultures. CONCLUSIONS: These data indicate that the HMG-CoA
      reductase inhibitor rosuvastatin has a favorable effect on diabetic neuropathy
      independent of its cholesterol-lowering effect. Our data provide evidence that
      this effect may be mediated in part via neuronal nitric oxide synthase/nitric
      oxide and phosphatidylinositol 3-kinase/Akt-signaling pathways and also suggest
      that restoration or preservation of the microcirculation of the sciatic nerve may
      be involved.

PMID- 15983250
TI  - In vivo cell seeding with anti-CD34 antibodies successfully accelerates
      endothelialization but stimulates intimal hyperplasia in porcine arteriovenous
      expanded polytetrafluoroethylene grafts.
AB  - BACKGROUND: The patency of AV expanded polytetrafluoroethylene (ePTFE) grafts for
      hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract.
      The absence of a functional endothelial monolayer on the prosthetic grafts is an
      important stimulus for IH. In the present study, we evaluated the feasibility of
      capturing endothelial progenitor cells in vivo using anti-CD34 antibodies on
      ePTFE grafts to inhibit IH in porcine AV ePTFE grafts. METHODS AND RESULTS: In 11
      pigs, anti-CD34-coated ePTFE grafts were implanted between the carotid artery and
      internal jugular vein. Bare ePTFE grafts were implanted at the contralateral
      side. After 3 (n=2) or 28 (n=9) days, the pigs were terminated, and the AV grafts
      were excised for histological analysis and SEM. At 3 and 28 days after
      implantation, 95% and 85% of the coated graft surface was covered by endothelial
      cells. In contrast, no cell coverage was observed in the bare graft at 3 days,
      whereas at 28 days, bare grafts were partly covered with endothelial cells (32%;
      P=0.04). Twenty-eight days after implantation, IH at the venous anastomosis was
      strongly increased in anti-CD34-coated grafts (5.96+/-1.9 mm2) compared with bare
      grafts (1.70+/-0.4 mm2; P=0.03). This increase in IH coincided with enhanced
      cellular proliferation at the venous anastomosis. CONCLUSIONS: Autoseeding with
      anti-CD34 antibodies results in rapid endothelialization within 72 hours. Despite
      persistent endothelial graft coverage, IH at the outflow tract is increased
      profoundly at 4 weeks after implantation. Further modifications are required to
      stimulate the protective effects of trapped endothelial cells.

PMID- 15983251
TI  - C-reactive protein and the 10-year incidence of coronary heart disease in older
      men and women: the cardiovascular health study.
AB  - BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary
      heart disease risk. Few long-term data in the elderly are available. METHODS AND
      RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age
      without prior vascular diseases; 26% had elevated concentrations (>3 mg/L). With
      10 years of follow-up, 547 participants developed coronary heart disease (CHD;
      defined as myocardial infarction or coronary death). With elevated CRP, the 10
      year cumulative CHD incidences were 33% in men and 17% in women. The age-,
      ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with
      <1 mg/L was 1.82 (95% CI, 1.46 to 2.28). Adjusting for conventional risk factors
      reduced the relative risk to 1.45 (95% CI, 1.14 to 1.86). The population
      attributable risk of CHD for elevated CRP was 11%. Risk relationships did not
      differ in subgroups defined by baseline risk factors. We assessed whether CRP
      improved prediction by the Framingham Risk Score. Among men with a 10-year
      Framingham-predicted risk of 10% to 20%, the observed CHD incidence was 32% for
      elevated CRP. Among women, CRP discriminated best among those with a 10-year
      predicted risk >20%; the incidences were 31% and 10% for elevated and normal CRP
      levels, respectively. CONCLUSIONS: In older men and women, elevated CRP was
      associated with increased 10-year risk of CHD, regardless of the presence or
      absence of cardiac risk factors. A single CRP measurement provided information
      beyond conventional risk assessment, especially in intermediate-Framingham-risk
      men and high-Framingham-risk women.

PMID- 15983252
TI  - Risk of embolism and death in infective endocarditis: prognostic value of
      echocardiography: a prospective multicenter study.
AB  - BACKGROUND: The incidence of embolic events (EE) and death is still high in
      patients with infective endocarditis (IE), and data about predictors of these 2
      major complications are conflicting. Moreover, the exact role of echocardiography
      in risk stratification is not well defined. METHODS AND RESULTS: In a multicenter
      prospective European study, including 384 consecutive patients (aged 57+/-17
      years) with definite IE according to Duke University criteria, we tested
      clinical, microbiological, and echocardiographic data as potential predictors of
      EE and 1-year mortality. Transesophageal echocardiography was performed in all
      patients. Embolism occurred before or after IE diagnosis (total-EE) in 131
      patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28
      patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently
      associated with total-EE, whereas vegetation length >10 mm and severe vegetation
      mobility were predictors of new-EE, even after adjustment for S aureus and S
      bovis. One-year mortality was 20.6%. In multivariable analysis, independently of
      the other predictors of death (age, female sex, creatinine serum >2 mg/L,
      moderate or severe congestive heart failure, and S aureus) and comorbidity,
      vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative
      risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). CONCLUSIONS: In IE, vegetation length is
      a strong predictor of new-EE and mortality. In combination with clinical and
      microbiological findings, echocardiography may identify high-risk patients who
      will need a more aggressive therapeutic strategy.

PMID- 15983253
TI  - Images in cardiovascular medicine. Ventricular septum rupture after myocardial
      infarction demonstrated by multislice computed tomography.

PMID- 15983254
TI  - Images in cardiovascular medicine. Right ventricular lead perforation presenting
      as left chest wall muscle stimulation.

PMID- 15983255
TI  - Posterior descending artery milking-like effect caused by ventricle
      pseudoaneurysm compression.

PMID- 15983256
TI  - Letter regarding article by Gage et al, "selecting patients with atrial
      fibrillation for anticoagulation: stroke risk stratification in patients taking
      aspirin".

PMID- 15983257
TI  - Letter regarding article by Ferriera et al, "postprandial hypertriglyceridemia
      increases circulating levels of endothelial cell microparticles".

PMID- 15983258
TI  - Defective ryanodine receptor interdomain interactions may contribute to
      intracellular Ca2+ leak: a novel therapeutic target in heart failure.

PMID- 15983259
TI  - Leaving neverland: a randomized trial for coarctation shows pediatric
      interventional cardiology is growing up.

PMID- 15983260
TI  - Interplay between apolipoprotein E and scavenger receptor class B type I controls
      coronary atherosclerosis and lifespan in the mouse.

PMID- 15983261
TI  - Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in
      the Insulin Resistance Atherosclerosis Study.
AB  - BACKGROUND: Subjects with type 2 diabetes have smaller LDL and HDL particles in
      addition to higher levels of triglycerides and lower HDL cholesterol. Elevated
      insulin resistance, blood pressure, and dyslipidemia (including small dense LDL)
      predicted incident diabetes. In the Insulin Resistance Atherosclerosis Study
      (IRAS) we studied nuclear magnetic resonance (NMR) lipoprotein particle measures
      in prediabetic individuals, considering potentially modifying covariates,
      including insulin resistance, as directly measured using a frequently sampled
      intravenous glucose tolerance test. METHODS AND RESULTS: Of 830 subjects who were
      nondiabetic at baseline, 130 (15.7%) developed diabetes after a mean follow-up of
      5.2 years. Various lipoprotein abnormalities were found in prediabetic subjects
      compared with subjects who stayed nondiabetic at follow-up. In logistic
      regression analyses (demographically adjusted), VLDL particles, large VLDL, LDL
      particles, small LDL, large HDL, small HDL, VLDL size, LDL size, and HDL size
      were related to incident diabetes. The relation of VLDL size and small HDL to
      incident diabetes was independent of waist (odds ratio [OR] [95% CI], 1.43 [1.18
      to 1.73] and 1.23 [1.01 to 1.51] for VLDL size and small HDL, respectively) and
      independent of conventionally (chemically) measured triglycerides and HDL
      cholesterol (OR [95% CI], 1.45 [1.18 to 1.78] and 1.30 [1.06 to 1.60],
      respectively). Insulin sensitivity attenuated the relation to incident diabetes
      of VLDL size (OR [95% CI], 1.25 [1.01 to 1.53]) but not of small HDL particles
      (OR [95% CI], 1.25 [1.02 to 1.54]). CONCLUSIONS: We have shown a range of
      lipoprotein abnormalities in prediabetic individuals, including compositional
      changes in HDL and VLDL. These findings extend previous work indicating a
      proatherogenic state in healthy, nondiabetic subjects who subsequently develop
      diabetes.

PMID- 15983262
TI  - Pathophysiology of coronary artery disease.
AB  - During the past decade, our understanding of the pathophysiology of coronary
      artery disease (CAD) has undergone a remarkable evolution. We review here how
      these advances have altered our concepts of and clinical approaches to both the
      chronic and acute phases of CAD. Previously considered a cholesterol storage
      disease, we currently view atherosclerosis as an inflammatory disorder. The
      appreciation of arterial remodeling (compensatory enlargement) has expanded
      attention beyond stenoses evident by angiography to encompass the biology of
      nonstenotic plaques. Revascularization effectively relieves ischemia, but we now
      recognize the need to attend to nonobstructive lesions as well. Aggressive
      management of modifiable risk factors reduces cardiovascular events and should
      accompany appropriate revascularization. We now recognize that disruption of
      plaques that may not produce critical stenoses causes many acute coronary
      syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to
      thrombosis. Alterations in circulating prothrombotic or antifibrinolytic
      mediators in the "fluid phase" of the blood can also predispose toward ACS.
      Recent results have established the multiplicity of "high-risk" plaques and the
      widespread nature of inflammation in patients prone to develop ACS. These
      findings challenge our traditional view of coronary atherosclerosis as a
      segmental or localized disease. Thus, treatment of ACS should involve 2
      overlapping phases: first, addressing the culprit lesion, and second, aiming at
      rapid "stabilization" of other plaques that may produce recurrent events. The
      concept of "interventional cardiology" must expand beyond mechanical
      revascularization to embrace preventive interventions that forestall future
      events.

PMID- 15983263
TI  - Report of the National Heart, Lung, and Blood Institute-National Institute of
      Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular
      Complications of Type 1 Diabetes Mellitus.

PMID- 15983264
TI  - Rebuilding an enduring trust in medicine: a global mandate: presidential address
      American Heart Association Scientific Sessions 2004.

PMID- 15983265
TI  - Linking health to social justice.

PMID- 15983266
TI  - Using the past to step forward: fetal alcohol syndrome in the Western Cape
      Province of South Africa.

PMID- 15983267
TI  - Public health nurses for Virginia's future: a collaborative project to increase
      the number of nursing students choosing a career in public health nursing.
AB  - A shift in the role of public health practice in the United States to population
      focused care, together with demographic shifts increasing the diversity and age
      of the population, has created a need for a public health workforce more highly
      skilled in community and population-based practices. Despite this need, few
      changes have been made in the pattern of field placements for nursing students,
      in part because many public health nurses in population-focused roles are
      unfamiliar with models of successful student fieldwork in their areas. We
      describe the Public Health Nurses for Virginia's Future project, a successful
      project undertaken by nurse educators and public health leaders to increase the
      number of highly qualified graduates working in state and local health
      departments.

PMID- 15983268
TI  - Ethical goals of community consultation in research.
AB  - In response to the traditional emphasis on the rights, interests, and well-being
      of individual research subjects, there has been growing attention focused on the
      importance of involving communities in research development and approval.
      Community consultation is a particularly common method of involving communities.
      However, the fundamental ethical goals of community consultation have not been
      delineated, which makes it difficult for investigators, sponsors, and
      institutional review boards to design and evaluate consultation efforts.
      Community consultation must be tailored to the communities in which it is
      conducted, but the purposes of consultation-the ethical goals it is designed to
      achieve-should be universal. We propose 4 ethical goals that give investigators,
      sponsors, institutional review boards, and communities a framework for evaluating
      community consultation processes.

PMID- 15983269
TI  - Sterilized in the name of public health: race, immigration, and reproductive
      control in modern California.
AB  - In exploring the history of involuntary sterilization in California, I connect
      the approximately 20,000 operations performed on patients in state institutions
      between 1909 and 1979 to the federally funded procedures carried out at a Los
      Angeles County hospital in the early 1970s. Highlighting the confluence of
      factors that facilitated widespread sterilization abuse in the early 1970s, I
      trace prosterilization arguments predicated on the protection of public health.
      This historical overview raises important questions about the legacy of eugenics
      in contemporary California and relates the past to recent developments in health
      care delivery and genetic screening.

PMID- 15983270
TI  - Rural definitions for health policy and research.
AB  - The term "rural" suggests many things to many people, such as agricultural
      landscapes, isolation, small towns, and low population density.However, defining
      "rural" for health policy and research purposes requires researchers and policy
      analysts to specify which aspects of rurality are most relevant to the topic at
      hand and then select an appropriate definition. Rural and urban taxonomies often
      do not discuss important demographic, cultural, and economic differences across
      rural places-differences that have major implications for policy and research.
      Factors such as geographic scale and region also must be considered. Several
      useful rural taxonomies are discussed and compared in this article. Careful
      attention to the definition of "rural" is required for effectively targeting
      policy and research aimed at improving the health of rural Americans.

PMID- 15983271
TI  - Which patients first? Setting priorities for antiretroviral therapy where
      resources are limited.
AB  - The availability of limited funds from international agencies for the purchase of
      antiretroviral (ARV) treatment in developing countries presents challenges,
      especially in prioritizing who should receive therapy. Public input and the
      protection of human rights are crucial in making treatment programs equitable and
      accountable. By examining historical precedents of resource allocation, we aim to
      provoke and inform debate about current ARV programs. Through a critical review
      of the published literature, we evaluate 4 precedents for key lessons: the
      discovery of insulin for diabetes in 1922, the release of penicillin for civilian
      use in 1943, the development of chronic hemodialysis programs in 1961, and
      current allocation of liver transplants. We then describe current rationing
      mechanisms for ARVs.

PMID- 15983272
TI  - Adolescent birth rates, total homicides, and income inequality in rich countries.
AB  - Income inequality has been associated with both homicides and births to
      adolescents in the United States and with homicides internationally. We found
      that adolescent birth rates and general homicide rates were closely correlated
      with each other internationally (r= 0.95) and within the United States (r = 0.74)
      and with inequality internationally and within the United States. These results,
      coupled with no association with absolute income, suggested that violence and
      births to adolescents may reflect gender-differentiated responses to low social
      status and could be reduced by reducing income inequality.

PMID- 15983273
TI  - Injuries at work in the US adult population: contributions to the total injury
      burden.
AB  - OBJECTIVES: We estimated the contribution of nonfatal work-related injuries on
      the injury burden among working-age adults (aged 18-64 years) in the United
      States. METHODS: We used the 1997-1999 National Health Interview Survey (NHIS) to
      estimate injury rates and proportions of work-related vs non-work-related
      injuries. RESULTS: An estimated 19.4 million medically treated injuries occurred
      annually to working-age adults (11.7 episodes per 100 persons; 95% confidence
      interval [CI]=11.3, 12.1); 29%, or 5.5 million (4.5 per 100 persons; 95% CI=4.2,
      4.7), occurred at work and varied by gender, age, and race/ethnicity. Among
      employed persons, 38% of injuries occurred at work, and among employed men aged
      55-64 years, 49% of injuries occurred at work. CONCLUSIONS: Injuries at work
      comprise a substantial part of the injury burden, accounting for nearly half of
      all injuries in some age groups. The NHIS provides an important source of
      population-based data with which to determine the work relatedness of injuries.
      Study estimates of days away from work after injury were 1.8 times higher than
      the Bureau of Labor Statistics (BLS) workplace-based estimates and 1.4 times as
      high as BLS estimates for private industry. The prominence of occupational
      injuries among injuries to working-age adults reinforces the need to examine
      workplace conditions in efforts to reduce the societal impact of injuries.

PMID- 15983274
TI  - Staffing and worker injury in nursing homes.
AB  - OBJECTIVES: We examined the relationship between nursing home staffing levels and
      worker injury rates in 445 nursing homes in 3 states. METHODS: We obtained First
      Reports of Injury and workers' compensation data from 3 states (Ohio, West
      Virginia, and Maryland) for the year 2000. We then linked these data to
      Medicare's Online Survey, Certification and Reporting system to obtain nursing
      home staffing details and organizational descriptors. We used ordinary least
      squares and log-transformed regression models to examine the association between
      worker injury rate and nursing home staffing and organizational characteristics.
      RESULTS: Total nursing hours per resident day were significantly associated with
      worker injury rates in nursing homes after we adjusted for organizational
      characteristics and state dummy variables (P=.0004). CONCLUSIONS: Our findings
      suggest that nursing home staffing levels have an important impact on worker
      health. These findings were supported for multiple facilities across different
      states; therefore, policies and resources that increase staffing levels in
      nursing homes are warranted.

PMID- 15983275
TI  - Occupational injury and absence from work among African American, Hispanic, and
      non-Hispanic White workers in the national longitudinal survey of youth.
AB  - OBJECTIVES: We examined how race and ethnicity influence injury and illness risk
      and number of days of work missed as a result of injury or illness. METHODS: We
      fit logistic regression and negative binomial regression models using generalized
      estimating equations with data from 1988 to 2000 on currently employed African
      American, Hispanic, and non-Hispanic White participants in the National
      Longitudinal Survey of Youth. RESULTS: Occupational factors-having a blue-collar
      occupation, working full-time, having longer tenure, working 1 job versus 2, and
      working the late shift-were associated with increased odds of an occupational
      injury or illness. Although racial/ethnic minority workers were no more likely
      than Whites to report an occupational injury or illness, they reported missing
      more days of work. African American and Hispanic men missed significantly more
      days of work than non-Hispanic White men, and African American women missed
      significantly more days of work than non-Hispanic White women. CONCLUSIONS:
      Factors associated with occupational health are multifaceted and complex. Our
      findings suggest that race/ethnicity influences the duration of work absence
      owing to injury or illness both indirectly (by influencing workers' occupational
      characteristics) and directly (by acting independently of occupational factors).

PMID- 15983276
TI  - Childhood socioeconomic position, educational attainment, and adult
      cardiovascular risk factors: the Aberdeen children of the 1950s cohort study.
AB  - OBJECTIVES: We assessed the associations of childhood socioeconomic position with
      cardiovascular disease risk factors (smoking, binge alcohol drinking, and being
      overweight) and examined the roles of educational attainment and cognitive
      functioning in these associations. METHODS: Data were derived from a cohort study
      involving 7184 individuals who were born in Aberdeen, Scotland, between 1950 and
      1956; had detailed records on perinatal characteristics, childhood anthropometry,
      and cognitive functioning; and responded to a mailed questionnaire when they were
      aged 45 to 52 years. RESULTS: Strong graded associations existed between social
      class at birth and smoking, binge drinking, and being overweight. Adjustment for
      educational attainment completely attenuated these associations. However, after
      control for adult social class, adult income and other potential confounding or
      mediating factors, some association remained. CONCLUSIONS: Educational attainment
      is an important mediating factor in the relation between socioeconomic adversity
      in childhood and smoking, binge drinking, and being overweight in adulthood.

PMID- 15983277
TI  - The health of poor women under welfare reform.
AB  - OBJECTIVES: We compared the health of single mothers affected by welfare reform
      with the health of a nationally representative sample of women to document the
      prevalence of poor health as single mothers experience the effects of welfare
      reform. METHODS: We compared risk factors and measures of health among women
      randomly sampled from the welfare rolls with similar data from a nationally
      representative sample of women. RESULTS: Women in our welfare recipient sample
      had higher rates of elevated glycosylated hemoglobin (> or = 6%; prevalence ratio
      [PR]=4.87; 95% confidence interval [CI]=2.69, 7.04), hypertension (systole > or =
      140 or diastole > or = 90; PR=2.36; 95% CI = 1.47, 3.24), high body mass index (
      > or = 30; PR = 1.78; 95% CI = 1.49, 2.08), and high-density lipoprotein
      cholesterol (< or = 35 mg/dL; PR=1.91; 95% CI=1.17, 2.65); lower peak expiratory
      flow; and less physical functioning. Current smoking rates were higher (PR =
      1.85; 95% CI = 1.50, 2.19) and smoking cessation rates were lower (PR=0.62; 95%
      CI=0.37, 0.86) than in the national sample. CONCLUSIONS: Current and former
      welfare recipients bear a substantial burden of illness. Further studies are
      necessary to interpret our findings of worsened health in the wake of welfare
      reform.

PMID- 15983278
TI  - To house or not to house: the effects of providing housing to homeless substance
      abusers in treatment.
AB  - OBJECTIVES: Housing typically is not provided to homeless persons during drug
      abuse treatment. We examined how treatment outcomes were affected under 3
      different housing provision conditions. METHODS: We studied 196 cocaine-dependent
      participants who received day treatment and no housing (NH), housing contingent
      on drug abstinence (ACH), or housing not contingent on abstinence (NACH). Drug
      use was monitored with urine testing. RESULTS: The ACH group had a higher
      prevalence of drug abstinence than the NACH group (after control for treatment
      attendance), which in turn had a higher prevalence than the NH group. All 3
      groups showed significant improvement in maintaining employment and housing.
      CONCLUSIONS: The results of this and previous trials indicate that providing
      abstinence-contingent housing to homeless substance abusers in treatment is an
      efficacious, effective, and practical intervention. Programs to provide such
      housing should be considered in policy initiatives.

PMID- 15983280
TI  - The annual physical: are physicians and patients telling us something?

PMID- 15983279
TI  - Written parental consent in school-based HIV/AIDS prevention research.
AB  - OBJECTIVES: We examined the process of obtaining "active," written parental
      consent for a school-based HIV/AIDS prevention project in a South African high
      school by investigating (1) parental consent form return rates, (2) parents'
      recall and knowledge of the research, and (3) the extent to which this consent
      procedure represented parents' wishes about their child's involvement in the
      research. METHODS: This cross-sectional descriptive study comprised interviews
      with parents of children in grades eight and nine in a poor, periurban settlement
      in Cape Town. RESULTS: Within 2 weeks, 94% of 258 parents responded to a letter
      requesting written consent and of those, 93% consented, but subsequent interviews
      showed that 65% remembered seeing the consent form. At the end of the interview,
      99% consented to their child's participation. CONCLUSIONS: These findings
      challenge many of the assumptions underlying active written parental consent.
      However, they should not be used to deny adolescents at high risk of HIV
      infection the opportunity to participate in prevention trials. Rather,
      researchers together with the communities in which the research is undertaken
      need to decide on appropriate informed consent strategies.

PMID- 15983282
TI  - Support of evidence-based guidelines for the annual physical examination: a
      survey of primary care providers.
AB  - BACKGROUND: Current evidence does not support an annual screening physical
      examination for asymptomatic adults, but little is known about primary care
      provider (PCP) attitudes and practices regarding an annual physical examination.
      METHODS: We conducted a postal survey (32 items) of attitudes and practices
      regarding the annual physical examination (in asymptomatic patients 18 years or
      older) of a random sample of PCPs (specializing in internal medicine, family
      practice, and obstetrics/gynecology) from 3 geographic areas (Boston, Mass;
      Denver, Colo; and San Diego, Calif). RESULTS: Respondents included 783 (47%) of
      1679 PCPs. Overall, 430 (65%) of 664 agreed that an annual physical examination
      is necessary. Three hundred ninety-three (55%) of 712 disagreed with the
      statement that national organizations do not recommend an annual physical
      examination, and 641 (88%) of 726 perform such examinations. Most PCPs agreed
      that an annual physical examination provides time to counsel patients about
      preventive health services (696/739 [94%]), improves patient-physician
      relationships (693/737 [94%]), and is desired by most patients (572/737 [78%]).
      Most also believe that an annual physical examination improves detection of
      subclinical illness (545/738 [74%]) and is of proven value (461/736 [63%]). Many
      believed that tests should be part of an annual physical examination, including
      mammography (44%), a lipid panel (48%), urinalysis (44%), testing of blood
      glucose level (46%), and complete blood cell count (39%). CONCLUSIONS: Despite
      contrary evidence, most PCPs believe an annual physical examination detects
      subclinical illness, and many report performing unproven screening laboratory
      tests. Primary care providers do not appear to accept recommendations that annual
      physical examinations be abandoned in favor of a more selective approach to
      preventing health problems.

PMID- 15983281
TI  - Systematic review and meta-analysis of short-acting insulin analogues in patients
      with diabetes mellitus.
AB  - BACKGROUND: This article compares the effect of treatment with short-acting
      insulin (SAI) analogues vs regular insulin on glycemic control, hypoglycemic
      episodes, quality of life, and diabetes-specific complications. METHODS:
      Electronic searches (Cochrane Library, MEDLINE, and EMBASE) and additional
      searching (pharmaceutical companies, experts, approval agencies, abstracts of
      diabetology meetings) were performed. Two reviewers independently screened
      randomized controlled trials to determine inclusion. RESULTS: Forty-two
      randomized controlled trials that assessed the effect of SAI analogues vs regular
      insulin in 7933 patients with type 1 diabetes mellitus, type 2 diabetes mellitus,
      and gestational diabetes mellitus were identified. The weighted mean difference
      between hemoglobin A(1c) values obtained using SAI analogues and regular insulin
      was -0.12% (95% confidence interval [CI], -0.17% to -0.07%) for adult patients
      with type 1 diabetes mellitus and -0.02% (95% CI, -0.10% to 0.07%) for patients
      with type 2 diabetes mellitus. The standardized mean difference for overall
      hypoglycemia (episodes per patient per month) was -0.05 (95% CI, -0.22 to 0.11)
      and -0.04 (95% CI, -0.12 to 0.04) comparing SAI analogues with regular insulin in
      adult patients with type 1 and type 2 diabetes mellitus, respectively. No
      differences between treatments were observed in children with type 1 diabetes,
      pregnant women with type 1 diabetes mellitus, and women with gestational
      diabetes. Concerning quality of life, improvement was observed only in open-label
      studies in patients with type 1 diabetes mellitus. No differences were seen in a
      double-blinded study of patients with type 1 or in the studies of patients with
      type 2 diabetes mellitus. CONCLUSION: Our analysis suggests only a minor benefit
      to hemoglobin A(1c) values in adult patients with type 1 diabetes mellitus but no
      benefit in the remaining population with type 2 or gestational diabetes from SAI
      analogue treatment.

PMID- 15983283
TI  - Quality of US outpatient care: temporal changes and racial/ethnic disparities.
AB  - BACKGROUND: The current national measure set for the quality of health care
      underrepresents the spectrum of outpatient care and makes limited use of readily
      available national ambulatory care survey data. METHODS: We examined 23
      outpatient quality indicators in 1992 and again in 2002 to measure overall
      performance and racial/ethnic disparities in outpatient care in the United
      States. The National Ambulatory Medical Care Survey and the National Hospital
      Ambulatory Medical Care Survey yielded information about ambulatory services
      provided in private physician offices and hospital outpatient departments,
      respectively. Quality indicator performance was defined as the percentage of
      applicable visits receiving appropriate care. RESULTS: In 2002, mean performance
      was 50% or more of applicable visits for 12 quality indicators, 7 of which were
      in the areas of appropriate antibiotic use and avoiding unnecessary routine
      screening. The performance of the remaining 11 indicators ranged from 15% to 42%.
      Overall, changes between 1992 and 2002 were modest, with significant improvements
      in 6 indicators: treatment of depression (47% vs 83%), statin use for
      hyperlipidemia (10% vs 37%), inhaled corticosteroid use for asthma in adults (25%
      vs 42%) and children (11% vs 36%), avoiding routine urinalysis during general
      medical examinations (63% vs 73%), and avoiding inappropriate medications in the
      elderly (92% vs 95%). After adjusting for potential confounders, race/ethnicity
      did not seem to affect quality indicator performance, except for greater
      angiotensin-converting enzyme inhibitor use for congestive health failure among
      blacks and less unnecessary antibiotic use for uncomplicated upper respiratory
      tract infections among whites. CONCLUSIONS: Measurable quality deficits and
      modest improvements across time call for greater adherence to evidence-based
      medicine in US ambulatory settings. Although significant racial disparities have
      been described in a variety of settings, we observed that similar, although less
      than optimal, care is being provided on a per-visit basis regardless of patient
      racial/ethnic background.

PMID- 15983284
TI  - Adverse drug event surveillance and drug withdrawals in the United States, 1969
      2002: the importance of reporting suspected reactions.
AB  - BACKGROUND: The Adverse Event Reporting System is the primary surveillance
      database used by the Food and Drug Administration for identifying postmarketing
      drug safety problems. METHODS: We analyzed all reports of suspected adverse drug
      reactions submitted to the Food and Drug Administration from the inception of the
      Adverse Event Reporting System database in 1969 through December 2002. We
      documented drug withdrawals and restricted distribution programs based on safety
      concerns. RESULTS: During the 33-year period from 1969 when adverse drug event
      reporting was initiated through 2002, about 2.3 million case reports of adverse
      events for the cumulative number of approximately 6000 marketed drugs were
      entered in the database. Most reports were for female patients. During this
      period, numerous drug reactions have been identified and added to the product
      labeling as boxed warnings, warnings, precautions, contraindications, and adverse
      reactions. More than 75 drugs/drug products have been removed from the market due
      to safety problems. In addition, 11 drugs have special requirements for
      prescriptions or have restricted distribution programs. Drugs withdrawn or
      restricted represent a small proportion (about 1%) of marketed drugs.
      CONCLUSIONS: The Food and Drug Administration's Adverse Event Reporting System is
      the primary surveillance database used for the identification of safety problems
      of marketed drugs. Despite the limitations of underreporting, differential
      reporting, and uneven quality, submitted reports often allow the identification
      of serious adverse events that are added to the product labeling information. In
      rare instances, additional regulations, up to and including market removal, have
      been required. We encourage physicians, pharmacists, other health care
      professionals, and patients to continue to report serious suspected and known
      adverse drug reactions to manufacturers and the Food and Drug Administration.

PMID- 15983285
TI  - Information and involvement preferences of women in their 40s before their first
      screening mammogram.
AB  - BACKGROUND: Informed decision making regarding screening mammography is
      recommended for women in their 40s; however, what information women want and how
      much involvement in decision making they prefer are not known. METHODS: Surveys
      were mailed to women aged 40 to 44 scheduled for their first screening mammogram.
      Women were members of a large New England health maintenance organization and
      received medical care at a multispecialty practice in the greater Boston area.
      Outcome measures included information needs and decisional control preferences.
      RESULTS: Ninety-six women responded. Of 93 identifying their ethnicity, 62 (67%)
      were white, 18 (19%) were black, 10 (11%) were Asian, 2 (2%) were Hispanic, and 1
      (1%) was other. Most (91% [85/93]) wanted their primary care provider to be the
      source of information regarding screening mammography. Information needs included
      the next steps to take if the mammogram result was abnormal (89%), how the woman
      would be contacted (75%), and how quickly (71%). Women also wanted to know about
      the harms of false-positive (84%) and false-negative (82%) results, benefits of
      screening in prolonging life (73%), and risk of getting breast cancer (69%). Most
      women preferred to make the screening decision after considering their medical
      provider's opinion (38%) or together with their medical provider (46%); fewer
      than 10% preferred that the decision be made by the woman or her provider alone.
      CONCLUSIONS: Women cited specific information needs before initiating screening
      mammography, including screening logistics and potential harms and benefits of
      screening. They also wanted to participate in the decision-making process.
      Effective methods should be developed for communicating desired information
      before screening.

PMID- 15983286
TI  - Impact of inadequate initial antimicrobial therapy on mortality in infections due
      to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by
      site of infection.
AB  - BACKGROUND: Infections due to extended-spectrum beta-lactamase-producing
      Escherichia coli and Klebsiella species (ESBL-EK) have increased markedly in
      recent years. Risk factors for mortality among ESBL-EK infections have not been
      studied. METHODS: This retrospective cohort study was conducted in a 625-bed
      tertiary care medical center and a 344-bed urban community hospital to determine
      whether inadequate initial antimicrobial therapy (IIAT) (>48 hours between the
      time a culture was obtained and initiation of an agent to which the infecting
      organism was susceptible) is associated with mortality in ESBL-EK infections. All
      hospitalized patients with an ESBL-EK infection between June 1, 1997, and
      December 31, 2002, were eligible for inclusion. Subsequently, we conducted a
      nested case-control study to identify risk factors for IIAT. RESULTS: Of 187
      subjects, 32 (17.1%) died while in the hospital. Clinical site of infection was a
      significant effect modifier in the association between IIAT and mortality. The
      presence of IIAT was an independent risk factor for mortality, but only for
      nonurinary ESBL-EK infections (adjusted odds ratio [95% confidence interval],
      10.04 [1.90-52.96]). Independent risk factors for IIAT were (1) infection with a
      multidrug-resistant ESBL-EK (ie, resistant to sulfamethoxazole-trimethoprim,
      aminoglycosides, and quinolones) (14.58 [1.91-111.36]) and (2) health care
      acquired ESBL-EK infection (4.32 [1.49-12.54]). CONCLUSIONS: Inadequate initial
      antimicrobial therapy is an independent risk factor for mortality in ESBL-EK
      infections, but only among nonurinary infections. Multidrug resistance was a
      strong risk factor for IIAT.

PMID- 15983287
TI  - Variations in coronary procedure utilization depending on body mass index.
AB  - BACKGROUND: Increased body mass index (BMI) (calculated as weight in kilograms
      divided by the square of height in meters) is a risk factor for coronary heart
      disease and is associated with lower preventive services utilization. The
      relationship between BMI and utilization of diagnostic or therapeutic procedures
      for coronary heart disease has not been examined. METHODS: We evaluated 109 664
      Medicare patients who were hospitalized for acute myocardial infarction in a
      nongovernmental acute care hospital between 1994 and 1996, were 65 years or
      older, and weighed 159 kg or less. We used logistic regression to examine the
      relationship of BMI with utilization of cardiac catheterization, percutaneous
      coronary intervention, and coronary artery bypass grafting while adjusting for
      patient and hospital characteristics. RESULTS: Participants had a mean age of
      75.8 years; 53% were men and 90% were white. Individuals with a BMI of 25.0 to
      35.0 had the highest rates of coronary procedure utilization. Compared with
      patients with a BMI of 25.0 to 29.9, those with a BMI of 35.0 to 39.9 had a
      reduced adjusted odds ratio (OR) of receiving coronary artery bypass grafting
      (OR, 0.88; 95% confidence interval [CI], 0.79-0.98), whereas patients with a BMI
      of 40.0 or greater had the lowest odds of receiving cardiac catheterization (OR,
      0.82; 95% CI, 0.73-0.92), percutaneous coronary intervention (OR, 0.89; 95% CI,
      0.77-1.03), and coronary artery bypass grafting (OR, 0.68; 95% CI, 0.57-0.82).
      Patients who did not receive coronary revascularization had higher mortality
      rates than those who did. CONCLUSIONS: For patients hospitalized with acute
      myocardial infarction, those with a very high BMI were less likely to receive
      invasive coronary procedures. Future research should investigate reasons for
      these variations in coronary procedure utilization.

PMID- 15983288
TI  - Effect of lowering of homocysteine levels on inflammatory markers: a randomized
      controlled trial.
AB  - BACKGROUND: Elevated concentrations of homocysteine and low concentrations of
      folate may lead to a proinflammatory state that could explain their relation to
      vascular disease risk. We investigated the effect of lowering homocysteine
      concentrations by means of folic acid supplementation on markers of inflammation.
      METHODS: In a double-blind, randomized, placebo-controlled trial among 530 men
      and postmenopausal women with homocysteine concentrations of 1.8 mg/L or higher
      (>/=13 micromol/L) at screening, we investigated the effect of folic acid
      supplementation (0.8 mg/d) vs placebo for 1 year on serum concentrations of C
      reactive protein, soluble intercellular adhesion molecule-1, oxidized low-density
      lipoprotein, and autoantibodies against oxidized low-density lipoprotein.
      RESULTS: After 1 year of supplementation, concentrations of serum folate
      increased by 400% (95% confidence interval [CI], 362%-436%), and those of
      homocysteine decreased by 28% (95% CI, 24%-36%) in the folic acid group compared
      with the placebo group. However, no changes in plasma concentrations of the
      inflammatory markers were observed. CONCLUSIONS: Although homocysteine is
      associated with vascular disease risk in the general population, marked lowering
      of slightly elevated homocysteine concentrations by means of 1-year folic acid
      supplementation does not influence inflammatory responses involving C-reactive
      protein, soluble intercellular adhesion molecule-1, oxidized low-density
      lipoprotein, and autoantibodies against oxidized low-density lipoprotein.

PMID- 15983289
TI  - Fasting triglyceride and the triglyceride-HDL cholesterol ratio are not markers
      of insulin resistance in African Americans.
AB  - BACKGROUND: The "lipid criteria" consist of a triglyceride (TG) level of 130
      mg/dL (1.47 mmol/L) or greater and a ratio of TG to high-density lipoprotein
      cholesterol (HDL-C) of 3 or greater. In Caucasians, the lipid criteria predict
      insulin resistance in individuals with a body mass index (BMI) of 25 kg/m(2) or
      greater. Our goal was to determine whether TG levels or TG-HDL-C ratio predicted
      insulin resistance in African Americans with a BMI of 25 kg/m(2) or more.
      METHODS: Of 125 African Americans, the 98 with a BMI of 25 kg/m(2) or more
      participated. All subjects had frequently sampled intravenous glucose tolerance
      tests with insulin resistance determined by the insulin sensitivity index.
      Subjects were divided into the following tertiles by insulin sensitivity: 12.8 to
      4.3, 4.2 to 2.3, and 2.2 to 0.2 mU/L per minute. Insulin resistance was defined
      as being in the third tertile. Across tertiles, the distribution of variables was
      compared by 1-way analysis of variance. Areas under the receiver operating
      characteristic curve were determined to identify variables that predicted insulin
      resistance. RESULTS: Fasting insulin level, BMI, and waist circumference
      increased across tertiles (all P<.01), but TG levels and TG-HDL-C ratio did not
      (all P>/=.3). The mean +/- SE areas under the curves for fasting insulin, BMI,
      and waist circumference were 0.85 +/- 0.04, 0.72 +/- 0.05, and 0.71 +/- 0.05,
      respectively. For TG level and TG-HDL-C ratio, the areas under the curves were
      0.55 +/- 0.06 and 0.56 +/- 0.06, respectively, meaning that the true-positive
      rate was nearly equal to the false-positive rate. Therefore, they could not be
      used as markers of insulin resistance. Furthermore, 17 subjects met the lipid
      criteria but only 7 were in the insulin-resistant tertile, making the sensitivity
      of these criteria to identify insulin resistance only 17%. CONCLUSION: In African
      Americans, TG levels and TG-HDL-C ratio are not reliable markers of insulin
      resistance.

PMID- 15983290
TI  - Clinical outcomes in antihypertensive treatment of type 2 diabetes, impaired
      fasting glucose concentration, and normoglycemia: Antihypertensive and Lipid
      Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
AB  - BACKGROUND: Optimal first-step antihypertensive drug therapy in type 2 diabetes
      mellitus (DM) or impaired fasting glucose levels (IFG) is uncertain. We wished to
      determine whether treatment with a calcium channel blocker or an angiotensin
      converting enzyme inhibitor decreases clinical complications compared with
      treatment with a thiazide-type diuretic in DM, IFG, and normoglycemia (NG).
      METHODS: Active-controlled trial in 31 512 adults, 55 years or older, with
      hypertension and at least 1 other risk factor for coronary heart disease,
      stratified into DM (n = 13 101), IFG (n = 1399), and NG (n = 17 012) groups on
      the basis of national guidelines. Participants were randomly assigned to double
      blind first-step treatment with chlorthalidone, 12.5 to 25 mg/d, amlodipine
      besylate, 2.5 to 10 mg/d, or lisinopril, 10 to 40 mg/d. We conducted an intention
      to-treat analysis of fatal coronary heart disease or nonfatal myocardial
      infarction (primary outcome), total mortality, and other clinical complications.
      RESULTS: There was no significant difference in relative risk (RR) for the
      primary outcome in DM or NG participants assigned to amlodipine or lisinopril vs
      chlorthalidone or in IFG participants assigned to lisinopril vs chlorthalidone. A
      significantly higher RR (95% confidence interval) was noted for the primary
      outcome in IFG participants assigned to amlodipine vs chlorthalidone (1.73 [1.10
      2.72]). Stroke was more common in NG participants assigned to lisinopril vs
      chlorthalidone (1.31 [1.10-1.57]). Heart failure was more common in DM and NG
      participants assigned to amlodipine (1.39 [1.22-1.59] and 1.30 [1.12-1.51],
      respectively) or lisinopril (1.15 [1.00-1.32] and 1.19 [1.02-1.39], respectively)
      vs chlorthalidone. CONCLUSION: Our results provide no evidence of superiority for
      treatment with calcium channel blockers or angiotensin-converting enzyme
      inhibitors compared with a thiazide-type diuretic during first-step
      antihypertensive therapy in DM, IFG, or NG.

PMID- 15983291
TI  - Effects of different blood pressure-lowering regimens on major cardiovascular
      events in individuals with and without diabetes mellitus: results of
      prospectively designed overviews of randomized trials.
AB  - BACKGROUND: Blood pressure (BP) level is a major determinant of cardiovascular
      morbidity and mortality in individuals with diabetes mellitus. Several guidelines
      recommend lower BP goals and specific drug classes for these patients. The
      overviews reported herein were performed to formally compare the effects on
      cardiovascular events and death of different BP-lowering regimens in individuals
      with and without diabetes. METHODS: Twenty-seven randomized trials (N = 158 709
      participants) that included 33 395 individuals with diabetes and 125 314 without
      diabetes contributed to these analyses. For each outcome and each comparison
      summary, estimates of effect and 95% confidence intervals were calculated for
      patients with and without diabetes using a random-effects model. The constancy of
      the effects of each treatment regimen in participants with and without diabetes
      was examined using chi(2) tests of homogeneity. RESULTS: Total major
      cardiovascular events were reduced to a comparable extent in individuals with and
      without diabetes by regimens based on angiotensin-converting enzyme inhibitors,
      calcium antagonists, angiotensin receptor blockers, and diuretics/beta-blockers
      (P > .19 for all by chi(2) test of homogeneity). There was limited evidence that
      lower BP goals produced larger reductions in total major cardiovascular events in
      individuals with vs without diabetes (P = .03 by chi(2) test of homogeneity).
      CONCLUSIONS: These overviews showed that the short- to-medium-term effects on
      major cardiovascular events of the BP-lowering regimens studied were broadly
      comparable for patients with and without diabetes. Different effects of regimens
      on intermediate renal outcomes not evaluated in these overviews may still provide
      a rationale for using specific drug classes in patients with diabetes.

PMID- 15983292
TI  - Relationships between symptoms and venous disease: the San Diego population
      study.
AB  - BACKGROUND: The associations between symptoms and venous disease of the lower
      extremities are poorly characterized. METHODS: We conducted a cross-sectional
      study to evaluate relationships between symptoms associated with venous disease
      and prevalent disease in 2408 men and women aged 29 to 91 years who were
      employees, retirees, or spouses at a large state university. Index participants
      were randomly selected within strata by age, sex, and ethnicity. A structured
      interview assessed the prevalence of aching, itching, heaviness, tired legs,
      cramping, swelling, and nighttime restless legs. A comprehensive standardized
      examination determined the prevalence of visible disease (normal,
      telangiectasias, varicose veins, and trophic changes) and functional disease
      (normal, superficial, and deep disease). We related symptoms to disease with
      attention to modification by sex, ethnicity, and age. RESULTS: Aching, itching,
      heaviness, tired legs, cramping, and swelling were related to both superficial
      and deep functional disease. The same symptoms were related to varicose veins and
      trophic changes. Swelling and heaviness were related to telangiectatic disease.
      Except for restless legs and trophic changes, the prevalence of symptoms across
      each category was greater in women than men. Aching was the most common symptom
      but was relatively nonspecific. Swelling was the most specific marker for
      prevalent visible and functional disease. Heaviness and itching also helped to
      distinguish prevalent disease. CONCLUSIONS: Venous symptoms were more prevalent
      in study participants with both visible and functional disease and in women.
      Swelling was the most specific predictor; heaviness, itching, and aching also
      helped to distinguish cases.

PMID- 15983293
TI  - Senile systemic amyloidosis presenting with heart failure: a comparison with
      light chain-associated amyloidosis.
AB  - BACKGROUND: Small deposits of amyloid are often found in the hearts of elderly
      patients. However, extensive deposition of transthyretin-derived amyloid fibrils
      in the heart (senile systemic amyloidosis [SSA]) can cause heart failure. The
      clinical features of SSA that involve the heart are ill defined, and the
      condition may be overlooked as a cause of heart failure. We sought to better
      define the clinical, echocardiographic, and electrocardiographic features of
      cardiac involvement in SSA and to compare them with the findings in patients with
      light chain-associated (AL) amyloidosis that affects the heart. METHODS: Eighteen
      consecutive patients with SSA and heart failure evaluated at a tertiary referral
      center for the diagnosis and treatment of amyloidosis were compared with 18
      randomly selected patients with AL amyloidosis that involved the heart. All
      patients underwent a complete clinical and biochemical evaluation.
      Echocardiograms and electrocardiograms were interpreted by blinded investigators.
      RESULTS: Patients with SSA were older than those with AL amyloidosis and were all
      male. Proteinuria (protein output of >1 g per 24 hours) was common in AL
      amyloidosis but was not present in SSA. Left ventricular wall thickness was
      greater in patients with SSA than those with AL amyloidosis, but despite thicker
      walls and older age, the severity of heart failure was less in the SSA group and
      the median survival was much longer (75 vs 11 months; P = .003). CONCLUSIONS:
      Senile systemic amyloidosis is a disorder of elderly men and is characterized by
      amyloidosis clinically limited to the heart. In contrast to the rapid progression
      of heart failure in AL amyloidosis, SSA results in slowly progressive heart
      failure. The difference in survival, despite evidence of more myocardial disease
      in the senile group, suggests that heart failure in AL amyloidosis may have a
      toxic component, possibly related to the circulating monoclonal light chain.

PMID- 15983294
TI  - Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a
      new threat to our antibiotic armamentarium.
AB  - BACKGROUND: Carbapenem antibiotics are used to treat serious infections caused by
      extended-spectrum beta-lactamase-carrying pathogens. Carbapenem resistance has
      been unusual in isolates of Klebsiella pneumoniae. In this study, the prevalence
      and molecular epidemiologic characteristics of carbapenem-resistant K pneumoniae
      are analyzed, and the experience involving 2 hospital outbreaks is described.
      METHODS: A citywide surveillance study was conducted in hospitals in Brooklyn. An
      observational study involving subsequent outbreaks at 2 hospitals was undertaken.
      Isolates were genetically fingerprinted by ribotyping and were examined for the
      presence of KPC-type carbapenem-hydrolyzing beta-lactamases. RESULTS: Of 602
      isolates of K pneumoniae collected during the citywide surveillance study, 45%
      had extended-spectrum beta-lactamases. Of the extended-spectrum beta-lactamase
      producing isolates, 3.3% carried the carbapenem-hydrolyzing beta-lactamase KPC-2.
      Several isolates were reported by the clinical microbiology laboratories as being
      susceptible to imipenem. Although all the isolates were resistant using agar
      diffusion methods, minimal inhibitory concentrations of imipenem were
      substantially lower for several isolates using standard broth microdilution tests
      and were highly dependent on the inoculum used. Two hospitals experienced the
      rapid spread of carbapenem-resistant isolates involving 58 patients. Overall 14
      day mortality for bacteremic patients was 47%. Most isolates belonged to a single
      ribotype. CONCLUSIONS: Carbapenem-resistant K pneumoniae isolates are rapidly
      emerging in New York City. The spread of a strain that possesses a carbapenem
      hydrolyzing beta-lactamase has occurred in regional hospitals. Because these
      isolates are resistant to virtually all commonly used antibiotics, control of
      their spread is crucial. However, automated systems used for susceptibility
      testing may not accurately identify all these isolates, which will severely
      hamper control efforts.

PMID- 15983295
TI  - Comments on a comprehensive strategy to prevent methicillin-resistant
      Staphylococcus aureus infections.

PMID- 15983296
TI  - Talking about death, dying, and bereavement with terminally ill patients and
      their caregivers.

PMID- 15983297
TI  - Diagnostic accuracy in systemic autoimmune diseases.

PMID- 15983298
TI  - Inconsistency in the editorial process in Archives of Internal Medicine?

PMID- 15983299
TI  - A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in
      patients with type 2 diabetes and dyslipidemia.
AB  - OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have
      different effects on lipids in patients with type 2 diabetes. However, these
      previous studies were either retrospective chart reviews or clinical trials not
      rigorously controlled for concomitant glucose- and lipid-lowering therapies. This
      study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.
      RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2
      diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not
      treated with any lipid-lowering agents). After a 4-week placebo washout period,
      subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30
      mg once daily for 12 weeks followed by 45 mg once daily for an additional 12
      weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated
      with 4 mg once daily followed by 4 mg twice daily for the same intervals.
      RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with
      pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P <
      0.001 between treatments). Additionally, the increase in HDL cholesterol was
      greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL
      cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for
      pioglitazone compared with rosiglitazone, respectively. LDL particle
      concentration was reduced with pioglitazone and increased with rosiglitazone (P <
      0.001). LDL particle size increased more with pioglitazone (P = 0.005).
      CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects
      on plasma lipids independent of glycemic control or concomitant lipid-lowering or
      other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is
      associated with significant improvements in triglycerides, HDL cholesterol, LDL
      particle concentration, and LDL particle size.

PMID- 15983300
TI  - Effect of raloxifene on serum triglycerides in women with a history of
      hypertriglyceridemia while on oral estrogen therapy.
AB  - OBJECTIVE: Raloxifene hydrochloride is a selective estrogen receptor modulator
      that to date has not been shown to cause hypertriglyceridemia in normal,
      diabetic, or hypertriglyceridemic women. This study was designed to assess the
      effect of raloxifene on serum triglycerides in postmenopausal women who have a
      history of increased hypertriglyceridemia with oral estrogen therapy. RESEARCH
      DESIGN AND METHODS: This was a single-center, uncontrolled, open-label study
      investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma
      lipids. The study subjects were 12 postmenopausal women, ages 49-73 years, with a
      documented history of oral estrogen-induced hypertriglyceridemia (serum
      triglycerides > or =3.39 mmol/l [> or =300 mg/dl]). RESULTS: At week 2 of the
      study, three (25%) of the subjects withdrew from the trial because they developed
      marked hypertriglyceridemia (>or =11.3 mmol/l [> or =1,000 mg/dl]) during
      raloxifene therapy. These three women had higher baseline triglyceride and
      glucose levels, were not being treated with lipid-lowering agents, and were more
      likely to have diabetes than the other study subjects. The remaining nine
      patients (75%) completed the 8-week trial and experienced a nonsignificant
      increase in mean triglyceride levels from baseline to end point. Raloxifene
      treatment also resulted in a significant 16% decrease in hepatic lipase activity
      and a 26% increase in HDL(2) levels (P = 0.013 and 0.03, respectively).
      CONCLUSIONS: Patients with a previous history of hypertriglyceridemia on oral
      estrogen therapy should have serum triglyceride levels monitored closely after
      beginning raloxifene therapy and may even require fibrate therapy before
      beginning raloxifene.

PMID- 15983301
TI  - The effect of rosiglitazone on overweight subjects with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of rosiglitazone in the
      treatment of overweight subjects with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: A total of 50 adult type 1 diabetic subjects with a baseline BMI > or
      =27 kg/m(2) were randomly assigned in a double-blind fashion to take insulin and
      placebo (n = 25) or insulin and rosiglitazone 4 mg twice daily (n = 25) for a
      period of 8 months. Insulin regimen and dosage were modified in all subjects to
      achieve near-normal glycemic control. RESULTS: Both groups experienced a
      significant reduction in HbA(1c) (A1C) level (rosiglitazone: 7.9 +/- 1.3 to 6.9
      +/- 0.7%, P < 0.0001; placebo: 7.7 +/- 0.8 to 7.0 +/- 0.9%, P = 0.002) and a
      significant increase in weight (rosiglitazone: 97.2 +/- 11.8 to 100.6 +/- 16.0
      kg, P = 0.008; placebo: 96.4 +/- 12.2 to 99.1 +/- 15.0, P = 0.016). Baseline
      measures of BMI (P = 0.001), total daily insulin dose (P = 0.002), total
      cholesterol (P = 0.005), HDL cholesterol (P = 0.001), and LDL cholesterol (P =
      0.02) were predictors of improvement in A1C level only in the group treated with
      rosiglitazone. Total daily insulin dose increased in subjects taking placebo
      (74.0 +/- 33.8 to 82.0 +/- 48.9 units, P < 0.05 baseline vs. week 32), but it
      decreased slightly in subjects taking rosiglitazone (77.5 +/- 28.6 to 75.3 +/-
      33.1 units). Both systolic blood pressure (137.4 +/- 15.6 vs. 128.8 +/- 14.8
      mmHg, baseline vs. week 32, P < 0.02) and diastolic blood pressure (87.2 +/- 9.4
      vs. 79.4 +/- 7.2 mmHg, P < 0.0001) improved in the group treated with
      rosiglitazone. The total incidence of hypoglycemia did not differ between groups.
      CONCLUSIONS: Rosiglitazone in combination with insulin resulted in improved
      glycemic control and blood pressure without an increase in insulin requirements,
      compared with insulin- and placebo-treated subjects, whose improved glycemic
      control required an 11% increase in insulin dose. Weight gain and hypoglycemia
      were similar in both groups at the end of the study. The greatest effect of
      rosiglitazone occurred in subjects with more pronounced markers of insulin
      resistance.

PMID- 15983302
TI  - A clinical trial of continuous subcutaneous insulin infusion versus multiple
      daily injections in older adults with type 2 diabetes.
AB  - OBJECTIVE: To compare the efficacy and safety of continuous subcutaneous insulin
      infusion (CSII) and multiple daily injection (MDI) in older adults with insulin
      treated type 2 diabetes and to assess treatment satisfaction and quality of life.
      RESEARCH DESIGN AND METHODS: Adults (n = 107) > or =60 years of age (mean age 66
      years) with insulin-treated type 2 diabetes (mean duration 16 years, BMI 32
      kg/m(2), and HbA(1C) [A1C] 8.2%) were randomized to CSII (using insulin lispro)
      or MDI (using insulin lispro and insulin glargine) in a two-center, 12-month,
      prospective, randomized, controlled clinical trial. Efficacy was assessed with
      A1C, safety by frequency of hypoglycemia, and treatment satisfaction and quality
      of life with the Diabetes Quality of Life Clinical Trial Questionnaire and the 36
      item short-form health survey, version 2. RESULTS: Forty-eight CSII subjects
      (91%) and 50 MDI subjects (93%) completed the study. Mean A1C fell by 1.7 +/-
      1.0% in the CSII group to 6.6% and by 1.6 +/- 1.2% in the MDI group to 6.4%. The
      difference in A1C between treatment groups was not statistically significant (P =
      0.20). Eighty-one percent of CSII subjects and 90% of MDI subjects experienced at
      least one episode of minor (self-treated) hypoglycemia (P = 0.17), and three CSII
      and six MDI subjects experienced severe hypoglycemia (P = 0.49). Rates of severe
      hypoglycemia were similarly low in the two groups (CSII 0.08 and MDI 0.23 events
      per person-year, P = 0.61). Weight gain did not differ between groups (P = 0.70).
      Treatment satisfaction improved significantly with both CSII and MDI (P <
      0.0001), and the difference between groups was not statistically significant (P =
      0.58). CONCLUSIONS: In older subjects with insulin-treated type 2 diabetes, both
      CSII and MDI achieved excellent glycemic control with good safety and patient
      satisfaction.

PMID- 15983303
TI  - Implementation and evaluation of a low-literacy diabetes education computer
      multimedia application.
AB  - OBJECTIVE: To evaluate a clinic-based multimedia intervention for diabetes
      education targeting individuals with low health literacy levels in a diverse
      population. RESEARCH DESIGN AND METHODS: Five public clinics in Chicago,
      Illinois, participated in the study with computer kiosks installed in waiting
      room areas. Two hundred forty-four subjects with diabetes were randomized to
      receive either supplemental computer multimedia use (intervention) or standard of
      care only (control). The intervention includes audio/video sequences to
      communicate information, provide psychological support, and promote diabetes self
      management skills without extensive text or complex navigation. HbA(1c) (A1C),
      BMI, blood pressure, diabetes knowledge, self-efficacy, self-reported medical
      care, and perceived susceptibility of complications were evaluated at baseline
      and 1 year. Computer usage patterns and implementation barriers were also
      examined. RESULTS: Complete 1-year data were available for 183 subjects (75%).
      Overall, there were no significant differences in change in A1C, weight, blood
      pressure, knowledge, self-efficacy, or self-reported medical care between
      intervention and control groups. However, there was an increase in perceived
      susceptibility to diabetes complications in the intervention group. This effect
      was greatest among subjects with lower health literacy. Within the intervention
      group, time spent on the computer was greater for subjects with higher health
      literacy. CONCLUSIONS: Access to multimedia lessons resulted in an increase in
      perceived susceptibility to diabetes complications, particularly in subjects with
      lower health literacy. Despite measures to improve informational access for
      individuals with lower health literacy, there was relatively less use of the
      computer among these participants.

PMID- 15983304
TI  - Decreased lung function in female but not male subjects with established cystic
      fibrosis-related diabetes.
AB  - OBJECTIVE: Although cystic fibrosis-related diabetes (CFRD) is associated with
      decreased lung function, sex is not known to influence CFRD. However, compared
      with male subjects with cystic fibrosis, female subjects with cystic fibrosis
      have increased morbidity. This study examines the association between female
      subjects with CFRD and poor lung function relative to male subjects using the
      percent predicted forced expiratory volume in 1 s (FEV(1)) as a surrogate measure
      of morbidity. RESEARCH DESIGN AND METHODS: We compared 323 patients with
      established CFRD with 489 cystic fibrosis control subjects with normal glucose
      tolerance (NGT) listed in the U.K. Cystic Fibrosis Database. Patients stratified
      by sex and chronic Pseudomonas aeruginosa infection were compared using binary
      logistic regression, and patients with new CFRD diagnoses were compared
      prospectively for the year 2002. RESULTS: CFRD in female subjects (but not male
      subjects) without chronic P. aeruginosa infection had a 20% lower percent
      predicted FEV(1) compared with control subjects with NGT (95% CI -11.7 to -27.7;
      P < 0.0001). Genotype, age, treatment center, age at diagnosis of cystic
      fibrosis, pregnancy, liver function, or dose of pancreatic enzyme replacement
      therapy did not confound this female disadvantage. Comparison of female subjects
      with newly diagnosed CFRD free of chronic P. aeruginosa infection with matched
      control subjects with NGT showed no FEV(1) disadvantage in the 1st year after
      CFRD diagnosis. CONCLUSIONS: Only female subjects with CFRD have significantly
      decreased lung function compared with sex-matched NGT control subjects. The
      absence of poor lung function in the first 12 months after diagnosis of diabetes
      suggests that an opportunity may exist to intervene and possibly prevent a
      decline in lung function, which can be as much as 20% in female subjects with
      CFRD.

PMID- 15983305
TI  - Should diabetes be considered a coronary heart disease risk equivalent?: results
      from 25 years of follow-up in the Renfrew and Paisley survey.
AB  - OBJECTIVE: The purpose of our study was to confirm or refute the view that
      diabetes be regarded as a coronary heart disease (CHD) risk equivalent and to
      test for sex differences in mortality. RESEARCH DESIGN AND METHODS: This was a
      prospective cohort study of 7,052 men and 8,354 women aged 45-64 years from
      Renfrew and Paisley, Scotland, who were first screened in 1972-1976 and followed
      for 25 years. All-cause mortality was calculated as death per 1,000 person-years.
      A Cox proportional hazards model was used to adjust survival for age, smoking
      habit, blood pressure, serum cholesterol, BMI, and social class. RESULTS: There
      were 192 deaths in 228 subjects with diabetes and 2,016 deaths in 3,076 subjects
      with CHD. The highest mortality was in the group with both diabetes and CHD
      (100.2 deaths/1,000 person-years in men, 93.6 in women) and the lowest in the
      group with neither (29.2 deaths/1,000 person-years in men, 19.4 in women). Men
      and women with diabetes only and CHD only formed an intermediate risk group. The
      adjusted hazard ratio (HR) for CHD mortality in men with diabetes only compared
      with men with CHD only was 1.17 (95% CI 0.78-1.74; P = 0.56). Corresponding HR
      for women was 1.97 (1.27-3.08; P = 0.003). CONCLUSIONS: Diabetes without previous
      CHD carries a lifetime risk of vascular death as high as that for CHD alone.
      Women may be at particular risk. Our data support the view that cardiovascular
      risk factors in diabetes should be treated as aggressively as in people with CHD.

PMID- 15983306
TI  - Is physician gender associated with the quality of diabetes care?
AB  - OBJECTIVE: This study examines the association between physician gender and
      diabetes quality of care. RESEARCH DESIGN AND METHODS: We examined the
      association between the gender of primary care physicians (n = 1,686) and the
      quality of diabetes care they provided to their patients participating in the
      Translating Research Into Action for Diabetes (TRIAD) study. Main outcome
      measures were diabetes processes of care including receipt of dilated retinal
      exams, urine microalbumin/protein testing, foot exams, lipid and HbA(1c) (A1C)
      testing, recommendation to take aspirin, and influenza vaccination over 1 year.
      Intermediate outcomes included blood pressure, A1C, LDL levels, and patient
      satisfaction. Hierarchical regression models accounted for clustering within
      provider groups and health plans and adjusted for patient age, gender, race,
      income, education, diabetes treatment and duration, and health status, along with
      physician age, years of practice, and specialty. RESULTS: Compared with male
      physicians (n = 1,213), female physicians (n = 473) were younger, had more
      recently completed training, and were more often internists. Patients of female
      physicians (n = 4,585) were more often women and younger than patients of male
      physicians (n = 1,783). In adjusted analyses, patients of female physicians were
      slightly more likely to receive lipid measurements (predicted probability 1.09
      [95% CI 1.02-1.15]) and A1C measurements (1.02 [1.00-1.05]) and were slightly
      more likely to have an LDL <130 mg/dl (1.05 [1.00-1.10]). CONCLUSIONS: Patients
      of female physicians received similar quality of care compared with patients of
      male physicians.

PMID- 15983307
TI  - Obesity, inactivity, and the prevalence of diabetes and diabetes-related
      cardiovascular comorbidities in the U.S., 2000-2002.
AB  - OBJECTIVE: Obesity and physical inactivity are established risk factors for type
      2 diabetes and cardiovascular comorbidities. Whether adiposity or fitness level
      is more important to health is controversial. The objective of this research is
      to determine the relative associations of physical activity and BMI with the
      prevalence of diabetes and diabetes-related cardiovascular comorbidities in the
      U.S. RESEARCH DESIGN AND METHODS: The Medical Expenditure Panel Survey (MEPS) is
      a nationally representative survey of the U.S. population. From 2000 to 2002,
      detailed information on sociodemographic characteristics and health conditions
      were collected for 68,500 adults. Normal weight was defined as BMI 18.5 to <25
      kg/m(2), overweight 25 to < or =30 kg/m(2), obese (class I and II) 30 to <40
      kg/m(2), and obese (class III) > or =40 kg/m(2). Physical activity was defined as
      moderate/vigorous activity > or =30 min > or =3 days per week. RESULTS: The
      likelihood of having diabetes and diabetes-related cardiovascular comorbidities
      increased with BMI regardless of physical activity and increased with physical
      inactivity regardless of BMI. Compared with normal-weight active adults, the
      multivariate-adjusted odds ratio (OR) for diabetes was 1.52 (95% CI 1.25-1.86)
      for normal-weight inactive adults and 1.65 (1.40-1.96) for overweight inactive
      adults; the OR for diabetes and comorbid hypertension was 1.71 (1.32-2.19) for
      normal-weight inactive adults and 1.84 (1.47-2.32) for overweight inactive
      adults. CONCLUSIONS: Both physical inactivity and obesity seem to be strongly and
      independently associated with diabetes and diabetes-related comorbidities. These
      results support continued research investigating the independent causal nature of
      these factors.

PMID- 15983308
TI  - Use of multisystemic therapy to improve regimen adherence among adolescents with
      type 1 diabetes in chronic poor metabolic control: a randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to determine whether multisystemic therapy
      (MST), an intensive, home-based psychotherapy, could improve adherence and
      metabolic control and decrease rates of hospital utilization among adolescents
      with chronically poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS:
      A randomized controlled trial was conducted with 127 adolescents with type 1
      diabetes and chronically poor metabolic control (HbA(1c) [A1C] > or =8% for the
      past year) who received their diabetes care in a children's hospital located in a
      major Midwestern city. Participants randomly assigned to MST received treatment
      for approximately 6 months. Data were collected at baseline and at 7 months
      posttest (i.e., treatment termination). Changes in A1C adherence, as measured by
      semistructured interviews and blood glucose meters and hospital admissions and
      emergency department visits, were assessed. RESULTS: In intent-to-treat analyses,
      participation in MST was associated with significant improvements in the
      frequency of blood glucose testing as assessed by blood glucose meter readings
      (F[1,125] = 16.75, P = 0.001) and 24-h recall interviews (F[1,125] = 6.70, P =
      0.011). Participants in MST also had a decreasing number of inpatient admissions,
      whereas the number of inpatient admissions increased for control subjects
      (F[1,125] = 6.25, P = 0.014). Per protocol analyses replicated intent-to-treat
      analyses but also showed a significant improvement in metabolic control for
      adolescents receiving MST compared with control subjects (F[1,114] = 4.03, P =
      0.047). CONCLUSIONS: Intensive, home-based psychotherapy improves the frequency
      of blood glucose testing and metabolic control and decreases inpatient admissions
      among adolescents with chronically poorly controlled type 1 diabetes.

PMID- 15983309
TI  - Hospitalizations, nursing home admissions, and deaths attributable to diabetes.
AB  - OBJECTIVE: To estimate all-cause hospitalizations, nursing home admissions, and
      deaths attributable to diabetes using a new methodology based on longitudinal
      data for a representative sample of older U.S. adults. RESEARCH DESIGN AND
      METHODS: A simulation model, based on data from the National Health and Nutrition
      Examination Survey (NHANES) I Epidemiologic Followup Study, was used to represent
      the natural history of diabetes and control for a variety of baseline risk
      factors. The model was applied to 6,265 NHANES III adults aged 45-74 years. The
      prevalence of risk factors in NHANES III, fielded in 1988-1994, better represents
      today's adults. RESULTS: For all NHANES III adults aged 45-74 years, a diagnosis
      of diabetes accounted for 8.6% of hospitalizations, 12.3% of nursing home
      admissions, and 10.3% of deaths in 1988-1994. For people with diabetes, diabetes
      alone was responsible for 43.4% of hospitalizations, 52.1% of nursing home
      admissions, and 47% of deaths. Adjusting for related cardiovascular conditions,
      which may provide more accurate estimates of attributable risks for people with
      diabetes, increased these estimates to 51.4, 57.1, and 56.8%, respectively.
      CONCLUSIONS: Risks of institutionalization and death attributable to diabetes are
      large. Efforts to translate recent trials of primary prevention into practice and
      continued efforts to prevent complications of diabetes could have a substantial
      impact on hospitalizations, nursing home admissions, and deaths and their
      societal costs.

PMID- 15983310
TI  - Psychosocial and socioeconomic risk factors for premature death in young people
      with type 1 diabetes.
AB  - OBJECTIVE: Mortality from acute diabetes-related events is greatly raised in
      young adults with type 1 diabetes. Psychosocial and socioeconomic risk factors
      are examined for deaths from acute events separately from deaths due to other
      causes. RESEARCH DESIGN AND METHODS: This study had a nested case-control design.
      The cases were patients from the Diabetes UK cohort who died before age 40 years.
      Deaths were categorized as acute events or chronic conditions related to
      diabetes. Where possible, two matched control subjects were selected for each
      case. Data relating to psychosocial and socioeconomic factors and variables
      related to diabetes complications were extracted from the case notes. Risks of
      death were estimated by calculation of odds ratios (ORs). RESULTS: Case notes
      were obtained for 98 case and 137 control subjects. Fifty-one deaths were
      attributed to acute causes, 34 to chronic conditions related to diabetes, and the
      remaining 13 were unrelated to diabetes. Living alone (OR 4.4), past drug abuse
      (5.7), and previous psychiatric referral (4.6) were all significantly associated
      with death from acute events but not death from chronic conditions. There was no
      association between deaths from acute events and nephropathy, hypertension,
      neuropathy, or retinopathy, although all of these were associated with deaths
      from chronic conditions. CONCLUSIONS: The results indicate that psychosocial
      factors are powerful risk factors for mortality from acute events in patients
      with type 1 diabetes, although not for mortality from chronic conditions. The
      data enable the identification of a high-risk group suitable for targeting with
      preventive measures to reduce acute event mortality.

PMID- 15983311
TI  - Web-based care management in patients with poorly controlled diabetes.
AB  - OBJECTIVE: To assess the effects of web-based care management on glucose and
      blood pressure control over 12 months in patients with poorly controlled
      diabetes. RESEARCH DESIGN AND METHODS: For this study, 104 patients with diabetes
      and HbA(1c) (A1C) > or =9.0% who received their care at a Department of Veterans
      Affairs medical center were recruited. All participants completed a diabetes
      education class and were randomized to continue with their usual care (n = 52) or
      receive web-based care management (n = 52). The web-based group received a
      notebook computer, glucose and blood pressure monitoring devices, and access to a
      care management website. The website provided educational modules, accepted
      uploads from monitoring devices, and had an internal messaging system for
      patients to communicate with the care manager. RESULTS: Participants receiving
      web-based care management had lower A1C over 12 months (P < 0.05) when compared
      with education and usual care. Persistent website users had greater improvement
      in A1C when compared with intermittent users (-1.9 vs. -1.2%; P = 0.051) or
      education and usual care (-1.4%; P < 0.05). A larger number of website data
      uploads was associated with a larger decline in A1C (highest tertile -2.1%,
      lowest tertile -1.0%; P < 0.02). Hypertensive participants in the web-based group
      had a greater reduction in systolic blood pressure (P < 0.01). HDL cholesterol
      rose and triglycerides fell in the web-based group (P < 0.05). CONCLUSIONS: Web
      based care management may be a useful adjunct in the care of patients with poorly
      controlled diabetes.

PMID- 15983312
TI  - Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic
      subjects: a 6-month, randomized, comparative trial.
AB  - OBJECTIVE: Despite the demonstrated benefits of glycemic control, patient
      acceptance of basal/bolus insulin therapy for type 1 diabetes has been slow. We
      investigated whether a basal/bolus insulin regimen involving rapid-acting, dry
      powder, inhaled insulin could provide glycemic control comparable with a
      basal/bolus subcutaneous regimen. RESEARCH DESIGN AND METHODS: Patients with type
      1 diabetes (ages 12-65 years) received twice-daily subcutaneous NPH insulin and
      were randomized to premeal inhaled insulin (n = 163) or subcutaneous regular
      insulin (n = 165) for 6 months. RESULTS: Mean glycosylated hemoglobin (A1C)
      decreased comparably from baseline in the inhaled and subcutaneous insulin groups
      (-0.3 and -0.1%, respectively; adjusted difference -0.16% [CI -0.34 to 0.01]),
      with a similar percentage of subjects achieving A1C <7%. Although 2-h
      postprandial glucose reductions were comparable between the groups, fasting
      plasma glucose levels declined more in the inhaled than in the subcutaneous
      insulin group (adjusted difference -39.5 mg/dl [CI -57.5 to -21.6]). Inhaled
      insulin was associated with a lower overall hypoglycemia rate but higher severe
      hypoglycemia rate. The overall hypoglycemia rate (episodes/patient-month) was 9.3
      (inhaled) vs. 9.9 (subcutaneous) (risk ratio [RR] 0.94 [CI 0.91-0.97]), and the
      severe hypoglycemia rate (episodes/100 patient-months) was 6.5 vs. 3.3 (RR 2.00
      [CI 1.28-3.12]). Increased insulin antibody serum binding without associated
      clinical manifestations occurred in the inhaled insulin group. Pulmonary function
      between the groups was comparable, except for a decline in carbon monoxide
      diffusing capacity in the inhaled insulin group without any clinical correlates.
      CONCLUSIONS: Inhaled insulin may provide an alternative for the management of
      type 1 diabetes as part of a basal/bolus strategy in patients who are unwilling
      or unable to use preprandial insulin injections.

PMID- 15983313
TI  - Relationship between testosterone levels, insulin sensitivity, and mitochondrial
      function in men.
AB  - OBJECTIVE: The goal of this study was to examine the relationship between serum
      testosterone levels and insulin sensitivity and mitochondrial function in men.
      RESEARCH DESIGN AND METHODS: A total of 60 men (mean age 60.5 +/- 1.2 years) had
      a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured
      using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by
      measuring maximal aerobic capacity (V(O2max)) and expression of oxidative
      phosphorylation genes in skeletal muscle. RESULTS: A total of 45% of subjects had
      normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2
      diabetes. Testosterone levels were positively correlated with insulin sensitivity
      (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had
      a BMI >25 kg/m(2) and a threefold higher prevalence of the metabolic syndrome
      than their eugonadal counterparts (n = 50); this relationship held true after
      adjusting for age and sex hormone-binding globulin but not BMI. Testosterone
      levels also correlated with V(O2max) (r = 0.43, P < 0.05) and oxidative
      phosphorylation gene expression (r = 0.57, P < 0.0001). CONCLUSIONS: These data
      indicate that low serum testosterone levels are associated with an adverse
      metabolic profile and suggest a novel unifying mechanism for the previously
      independent observations that low testosterone levels and impaired mitochondrial
      function promote insulin resistance in men.

PMID- 15983314
TI  - Determinants of exercise capacity in patients with type 2 diabetes.
AB  - OBJECTIVE: Type 2 diabetes is associated with reduced exercise capacity, but the
      cause of this association is unclear. We sought the associations of impaired
      exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS: Subclinical
      left ventricular (LV) dysfunction was sought from myocardial strain rate and the
      basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2
      diabetes (aged 56 +/- 10 years, 91 men), good quality echocardiographic images,
      and negative exercise echocardiograms. The same measurements were made in 56
      control subjects (aged 53 +/- 10 years, 29 men). Exercise capacity was calculated
      in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart
      rate difference between peak and 1 min after exercise. In subjects with type 2
      diabetes, exercise capacity was correlated with clinical, therapeutic,
      biochemical, and echocardiographic variables, and significant independent
      associations were sought using a multiple linear regression model. RESULTS:
      Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2
      diabetes. Exercise capacity was associated with age (r = -0.37, P < 0.001), male
      sex (r = 0.26, P = 0.001), BMI (r = -0.19, P = 0.012), HbA(1c) (A1C; r = -0.22, P
      = 0.009), Em (r = 0.43, P < 0.001), HRR (r = 0.42, P < 0.001), diabetes duration
      (r = -0.18, P = 0.021), and hypertension history (r = -0.28, P < 0.001). Age (P <
      0.001), male sex (P = 0.007), BMI (P = 0.001), Em (P = 0.032), HRR (P = 0.013),
      and A1C (P = 0.0007) were independent predictors of exercise capacity.
      CONCLUSIONS: Reduced exercise capacity in patients with type 2 diabetes is
      associated with diabetes control, subclinical LV dysfunction, and impaired HRR.

PMID- 15983315
TI  - Impact of overweight on chronic microvascular complications in type 1 diabetic
      patients.
AB  - OBJECTIVE: To investigate a possible association of BMI with retinopathy and
      neuropathy in type 1 diabetes. Retinopathy and neuropathy may not only be related
      to glycemic control and diabetes duration but also to blood pressure and BMI.
      RESEARCH DESIGN AND METHODS: A total of 592 type 1 diabetic patients without
      nephropathy were studied (M/F: 324/268; age: 41 +/- 12 years; duration: 19 +/- 11
      years; HbA(1c) [A1C]: 7.9 +/- 1.1%). Patients were subdivided according to BMI:
      168 men and 146 women with BMI <25 kg/m(2), and 156 men and 122 women with BMI >
      or =25 kg/m(2). Retinopathy was examined by fundoscopy and neuropathy by
      electromyography. RESULTS: Hypertension (>130/85 mmHg) was present in 40%,
      retinopathy in 53%, and neuropathy in 43% of patients. Overweight subjects had
      more retinopathy (63 vs. 45%, P < 0.0001, odds ratio [OR] = 2.1) and neuropathy
      (49 vs. 38%, P = 0.008, OR = 1.6) than normal-weight patients. Patients with
      retinopathy were older (45 +/- 12 vs. 37 +/- 11 years, P < 0.0001) and had a
      longer diabetes duration (25 +/- 10 vs. 12 +/- 8 years, P < 0.0001), a higher A1C
      (8.0 +/- 1.1 vs. 7.7 +/- 1.1%, P = 0.001), and a higher BMI (25.8 +/- 4.1 vs.
      24.7 +/- 4.2 kg/m(2), P = 0.001) than individuals without retinopathy. The same
      results are found in neuropathy. Logistic regression analysis showed that
      diabetes duration (beta = 0.15, P < 0.0001), blood pressure (beta = 0.22, P =
      0.0047), and A1C (beta = 0.24, P = 0.01), but not BMI, lipid levels, sex, or age,
      were independent risk factors for retinopathy. Likewise, duration (beta = 0.05, P
      < 0.0001), age (beta = 0.04, P = 0.0001), A1C (beta = 0.35, P < 0.0001), and sex
      (beta = 0.74, P = 0.0001) but not BMI, lipid levels, or hypertension were
      independently associated with neuropathy. Men had more neuropathy than women (50
      vs. 34%, P < 0.0001, OR = 1.9). Leptin and adiponectin levels did not differ
      between individuals with or without microvascular complications. CONCLUSIONS:
      Retinopathy and neuropathy are more prevalent in overweight (BMI > or =25
      kg/m(2)) type 1 diabetic subjects. However, logistic regression analysis showed
      that diabetes duration and A1C remain the main determinants for retinopathy and
      neuropathy.

PMID- 15983316
TI  - Increased heat generation from atherosclerotic plaques in patients with type 2
      diabetes: an increased local inflammatory activation.
AB  - OBJECTIVE: Patients with coronary artery disease (CAD) and diabetes show
      increased inflammatory activation. Thermography detects local inflammatory
      involvement as heat generation. The aim of this study was to investigate whether
      patients with CAD and diabetes have increased local heat generation compared with
      nondiabetic patients. RESEARCH DESIGN AND METHODS: We enrolled patients
      undergoing percutaneous coronary interventions: 45 diabetic patients and 63
      nondiabetic patients, serving as the control group, matched for age, type of
      clinical syndrome, statin and aspirin intake, and angiographic stenosis (%).
      Coronary thermography was performed, and temperature difference (DeltaT) between
      the atherosclerotic plaque and the proximal vessel wall was measured. RESULTS:
      Patients with diabetes had increased temperature difference compared with
      nondiabetic patients (DeltaT: 0.17 +/- 0.18 degrees C vs. 0.09 +/- 0.02 degrees
      C, P = 0.01). Twenty-one diabetic and 22 nondiabetic patients suffered from acute
      coronary syndromes (ACSs) (P = 0.22). Patients with diabetes and ACSs had
      increased temperature difference compared with nondiabetic patients with ACSs
      (DeltaT: 0.29 +/- 0.31 degrees C vs. 0.15 +/- 0.21 degrees C, P = 0.02), which is
      the same as patients with diabetes and chronic stable angina (DeltaT: 0.09 +/-
      0.08 degrees C vs. 0.05 +/- 0.04 degrees C, P = 0.006). Twenty-three diabetic and
      30 nondiabetic patients were under therapy with statins (P = 0.72). Patients with
      diabetes under statins had lower temperature difference compared with untreated
      patients (DeltaT: 0.11 +/- 0.12 degrees C vs. 0.22 +/- 0.21 degrees C, P = 0.02),
      which is the same as nondiabetic patients under statins (DeltaT: 0.05 +/- 0.04
      degrees C vs. 0.13 +/- 0.18 degrees C, P = 0.01). CONCLUSIONS: Patients with
      diabetes have increased temperature difference compared with nondiabetic
      patients. Patients with diabetes under statins showed decreased temperature
      difference compared with untreated patients, suggesting that statins have a
      favorable effect in patients with diabetes and CAD.

PMID- 15983317
TI  - Noninvasive diagnosis of coronary artery disease in patients with diabetes by
      dobutamine stress real-time myocardial contrast perfusion imaging.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy of real-time
      myocardial contrast perfusion imaging (MCPI) during dobutamine stress in the
      diagnosis and localization of coronary artery disease (CAD) in patients with
      diabetes. Myocardial contrast echocardiography is a new technique that allows
      evaluation of myocardial perfusion. Its utility in diabetic patients has not been
      defined. RESEARCH DESIGN AND METHODS: Dobutamine-atropine stress test was
      performed in conjunction with MCPI using Optison or Definity at rest and at peak
      stress in 128 patients with diabetes and suspected CAD who underwent coronary
      angiography within 1 month. CAD was defined as > or =50% stenosis in one or more
      coronary artery. MCPI was considered diagnostic of CAD in the presence of
      reversible perfusion abnormalities. The normalcy rate of MCPI was additionally
      determined in 18 asymptomatic nondiabetic patients with low probability. RESULTS:
      CAD was detected in 101 (79%) patients by angiography. Reversible perfusion
      abnormalities were detected in 90 patients with and 13 patients without CAD. The
      overall sensitivity of MCPI was 89% (95% CI 83-95), specificity 52% (33-71), and
      accuracy 81% (75-88). Reversible abnormalities were detected in two or more
      vascular distributions in 44 of 56 patients with multivessel CAD and in 8 of 63
      patients without (sensitivity 68%, specificity 87%, positive predictive value
      84%, and accuracy 79%). Regional sensitivity was 75% (65-85) for left anterior
      descending CAD, 71% (60-83) for left circumflex, and 67% (55-78) for right CAD.
      MCPI was normal in 16 of the 18 patients with low clinical probability of CAD
      (normalcy rate 89%). CONCLUSIONS: MCPI is a useful noninvasive technique for the
      diagnosis and localization of CAD in diabetic patients. The extent of perfusion
      abnormalities can identify patients with multivessel CAD with a moderate
      sensitivity and high specificity.

PMID- 15983318
TI  - The effect of statin therapy on endothelial function in type 2 diabetes without
      manifest cardiovascular disease.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the most important cause of mortality
      in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow
      mediated dilation (FMD) is a noninvasive technique for measuring endothelial
      dysfunction. We aimed to determine the effect of long-term statin therapy versus
      placebo on FMD in patients with type 2 diabetes without manifest CVD. RESEARCH
      DESIGN AND METHODS: A randomized, placebo-controlled, double-blind trial was
      performed with 250 type 2 diabetic patients. Patients were given 0.4 mg
      cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn
      from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin,
      without deblinding the study. The primary end point was the change in FMD,
      measured by B-mode ultrasound, after 2 years. RESULTS: Determinants of baseline
      FMD were diabetes duration, common carotid intima-media thickness, and brachial
      artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the
      statin group and did not change significantly after 2 years. CONCLUSIONS: The 2
      year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced
      improvement of cardiovascular risk in patients with type 2 diabetes may be
      mediated through mechanisms other than increased nitric oxide availability.

PMID- 15983319
TI  - No effect of statin therapy on silent myocardial ischemia in patients with type 2
      diabetes without manifest cardiovascular disease.
AB  - OBJECTIVE: Coronary artery disease is the most important cause of mortality in
      patients with type 2 diabetes. We aimed to determine the prevalence of silent
      myocardial ischemia (SMI) and the effect of statin therapy on SMI in type 2
      diabetic patients without manifest cardiovascular disease. RESEARCH DESIGN AND
      METHODS: A randomized, placebo-controlled, double-blind trial was performed in
      250 patients with type 2 diabetes without manifest cardiovascular disease.
      Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001,
      when cerivastatin was withdrawn from the market, cerivastatin 0.4 mg was replaced
      by 20 mg simvastatin without deblinding the study. The primary end point was the
      change in ischemic episodes, duration, and burden as measured by 48-h ambulatory
      electrocardiography (AECG) over 2 years. RESULTS: At baseline, 47 of 233 (20%)
      evaluable ambulatory electrocardiograms showed evidence of ischemia. After 2
      years, there was a trend toward more ischemia in both treatment groups, without
      significant differences between the changes in ischemic parameters (episodes P =
      0.498; duration P = 0.697; burden P = 0.798) in the two treatment groups.
      Cardiovascular events occurred in 12 patients in the placebo group and in two
      patients in the statin group (P = 0.006). There was no relationship between these
      cardiovascular events and the presence of SMI at baseline. CONCLUSIONS: SMI
      occurred in 20% of type 2 diabetes patients without manifest cardiovascular
      disease. There was no effect from 2 years of statin therapy on SMI. In contrast,
      we observed a significantly lower cardiovascular event rate on statin therapy.
      AECG may not be a proper tool for risk stratification in patients with type 2
      diabetes.

PMID- 15983320
TI  - Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial
      infarction: insights from the National Heart Care Project.
AB  - OBJECTIVE: Thiazolidinediones (TZDs) and metformin are insulin-sensitizing
      antihyperglycemic agents with reported benefits on atherosclerosis. Despite
      extensive use in patients with diabetes and cardiovascular disease, there is a
      paucity of outcomes data with metformin and none yet with TZDs. We sought to
      determine the impact of these insulin sensitizers on outcomes in diabetic
      patients after hospitalization with acute myocardial infarction (AMI). RESEARCH
      DESIGN AND METHODS: We conducted a retrospective cohort study of 24,953 Medicare
      beneficiaries with diabetes discharged after hospitalization with AMI between
      April 1998 and March 1999 or July 2000 and June 2001. The independent association
      between discharge prescription for metformin, TZD, or both agents and outcomes at
      1 year was assessed in multivariable Cox proportional hazards models, adjusting
      for patient, physician, and hospital variables. The primary outcome was time to
      death within 1 year of discharge; secondary outcomes were time to first
      rehospitalization within 1 year of discharge for AMI, heart failure, and all
      causes. RESULTS: There were 8,872 patients discharged on an antihyperglycemic
      agent, of which 819 were prescribed a TZD, 1,273 metformin, and 139 both drugs.
      After multivariable analysis, compared with patients prescribed an
      antihyperglycemic regimen that included no insulin sensitizer, mortality rates
      were not significantly different in patients treated with either metformin
      (hazard ratio [HR] 0.92 [95% CI 0.81-1.06]) or a TZD (0.92 [0.80-1.05]) but were
      lower in those prescribed both drugs (0.52 [0.34-0.82]). The results were similar
      among patients with heart failure. The prescription of a TZD was associated with
      a borderline higher risk of all-cause readmission (1.09[1.00-1.20]),
      predominately due to a higher risk for heart failure readmission (1.17 [1.05
      1.30]). CONCLUSIONS: Individually, prescription of insulin-sensitizing drugs is
      not associated with a significantly different risk of death in older diabetic
      patients within 1 year following AMI compared with other antihyperglycemic
      agents. Combined, however, metformin and TZDs may exert benefit. TZD prescription
      is associated with a higher risk of readmission for heart failure after
      myocardial infarction.

PMID- 15983322
TI  - Race-specific differences in antioxidant enzyme activity in patients with type 2
      diabetes: a potential association with the risk of developing nephropathy.
AB  - OBJECTIVE: Lipid hydroperoxide, a marker of oxidative stress, is linked to the
      development of nephropathy and is reportedly higher in patients of African origin
      compared with Caucasians. This may be relevant to race-specific differences in
      susceptibility to nephropathy. We investigated whether alterations in antioxidant
      enzyme activity could account for this biochemical phenotype and examined the
      relationship with conventional markers of renal disease. RESEARCH DESIGN AND
      METHODS: Two hundred seventeen individuals were studied. Patients with type 2
      diabetes (n = 75) of African and Caucasian origin were matched by sex and racial
      origin with healthy control subjects (n = 142). Plasma total superoxide dismutase
      (SOD) and glutathione peroxidase (GPx) activity were spectrophotometrically
      measured, and total cholesterol and triglycerides were measured by enzymatic
      methods. RESULTS: SOD activity was higher and GPx activity lower in patients with
      diabetes than in healthy control subjects (573 +/- 515 vs. 267 +/- 70 units/l, P
      < 0.001 and 150 +/- 93 vs. 178 +/- 90 units/l, P = 0.019, respectively). Patients
      of African origin with diabetes had lower GPx and higher SOD activity compared
      with Caucasian patients (126 +/- 82 vs. 172 +/- 97 units/l, P = 0.03 and 722 +/-
      590 vs. 445 +/- 408 units/l, P = 0.002, respectively). Patients of African origin
      with normal urinary albumin excretion had significantly higher plasma creatinine
      concentrations (100.7 +/- 14.2 vs. 88.1 +/- 14.9 micromol/l, P = 0.007) and lower
      GPx activity (99.0 +/- 72.4 vs. 173.7 +/- 107.4 units/l, P = 0.02) compared with
      those of Caucasian origin. African origin was an independent predictor of
      elevated SOD (P = 0.007) and reduced GPx activity (P = 0.02) in regression
      analysis. CONCLUSIONS: SOD and GPx enzyme activities vary according to race and
      could account for differences in lipid hydroperoxide. In patients of African
      origin, susceptibility to renal disease may be associated with lowered GPx
      activity.

PMID- 15983321
TI  - Effects of irbesartan on intracellular antioxidant enzyme expression and activity
      in adolescents and young adults with early diabetic angiopathy.
AB  - OBJECTIVE: Defective intracellular antioxidant enzyme production (IAP) has been
      demonstrated in adults with diabetic nephropathy. The objective of this study was
      to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on
      IAP in adolescents and young adults with type 1 diabetes and early signs of
      retinopathy and nephropathy. RESEARCH DESIGN AND METHODS: This prospective,
      matched case-control study was conducted between November 2001 and December 2002
      among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21
      years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10
      healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin
      biopsies from the anterior part of the forearm and cultured in Dulbecco's
      modified Eagle's medium. The activity and mRNA expression of CuZn superoxide
      dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and
      glutathione peroxidase (GPX) were measured before and after 6 months of treatment
      with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was
      evaluated at different glucose concentrations (5 and 22 mmol/l). RESULTS: At a
      normal glucose concentration (5 mmol/l), the activity and mRNA expression of
      CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3
      phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07
      mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/-
      0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three
      groups (only values of diabetic subjects with angiopathy are shown). At high
      glucose concentrations, the activity and mRNA expression of CuZnSOD increased
      similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26
      units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only
      control subjects and diabetic subjects without angiopathy (diabetic subjects with
      angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10
      units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any
      group. Treatment with irbesartan in adolescents with diabetic angiopathy was able
      to restore CAT and GPX activity and mRNA expression after exposure to high
      glucose concentrations. Markers of oxidative stress (serum malondialdehyde,
      fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1,
      and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after
      treatment with irbesartan. CONCLUSIONS: Adolescents and young adults with early
      signs of diabetic angiopathy have defective intracellular antioxidant enzyme
      production and activity. Treatment with irbesartan can substantially improve the
      activity and production of these enzymes in skin fibroblasts.

PMID- 15983323
TI  - Effect of hepatic lipase -514C->T polymorphism and its interactions with
      apolipoprotein C3 -482C->T and apolipoprotein E exon 4 polymorphisms on the risk
      of nephropathy in chinese type 2 diabetic patients.
AB  - OBJECTIVE: Triglyceride-rich lipoprotein particles may promote the progression of
      diabetic nephropathy. Patients with diabetic nephropathy have increased plasma
      triglycerides and reduced activity of hepatic lipase (HL), which hydrolyzes
      triglycerides. We hypothesized that the HL -514C-->T polymorphism, which reduces
      HL expression, and its interactions with polymorphisms in apolipoprotein (apo) E
      and apoC3 increase the risk of diabetic nephropathy. RESEARCH DESIGN AND METHODS:
      In a case-control study involving 374 Chinese type 2 diabetic patients with and
      392 without diabetic nephropathy, we genotyped the HL -514C-->T, apoE exon 4, and
      apoC3 -482C-->T polymorphisms. RESULTS: HL -514T-containing genotypes (T+) were
      associated with diabetic nephropathy (OR = 1.7, P = 0.0009). Adjustment by
      multiple logistic regression for hypertension, triglycerides, sex, non-HDL
      cholesterol, BMI, smoking, and alcohol intake did not diminish the association
      (OR = 1.8, P = 0.003). The association between HL T+ genotypes and diabetic
      nephropathy appeared stronger in diabetic patients with apoC3 -482 non-TT
      genotypes (OR = 1.9, P = 0.003) or apoE epsilon2 or epsilon4 alleles (OR = 2.2, P
      = 0.005). Subjects with HL TT exhibited trends toward increased triglyceride and
      non-HDL cholesterol levels compared with CC carriers. CONCLUSIONS: HL T+
      genotypes might increase the risk of developing diabetic nephropathy by slowing
      clearance of triglyceride-rich remnant lipoproteins. In concert with other risk
      factors (e.g., hyperglycemia), lipid abnormalities may damage the kidneys and
      endothelium, where reduced binding sites for lipases may precipitate a vicious
      cycle of dyslipidemia, proteinuria, and nephropathy.

PMID- 15983324
TI  - Peripheral total and differential leukocyte count in diabetic nephropathy: the
      relationship of plasma leptin to leukocytosis.
AB  - OBJECTIVE: Because of increasing evidence that white blood cells (WBCs) play a
      role in the development and progression of diabetes complications, this study
      aimed to investigate the relation of circulating total and differential leukocyte
      counts to nephropathy in patients with type 2 diabetes. Plasma leptin levels were
      also measured to investigate their role in peripheral leukocytosis. RESEARCH
      DESIGN AND METHODS: For this study, 1,480 subjects with type 2 diabetes who were
      enrolled in a disease management program were stratified according to urinary
      microalbumin and serum creatinine measurements. The total and differential
      leukocyte profiles of peripheral blood were measured and plasma leptin was
      examined by enzyme-linked immunosorbent assay. Demographic and potential
      metabolic confounding factors were analyzed with linear and logistic regression
      to calculate the effects of leukocyte count on diabetic nephropathy. RESULTS: The
      peripheral total WBC, monocyte, and neutrophil counts increased in parallel with
      the advancement of diabetic nephropathy. In contrast, the lymphocyte count
      decreased. When WBC counts were analyzed per quartile and as continuous variables
      after adjusting for age, sex, and other known risk factors with multiple
      regression analysis, peripheral total WBC, monocyte, neutrophil, and lymphocyte
      counts were independently and significantly associated with diabetic nephropathy.
      Plasma leptin levels increased in patients with nephropathy and correlated
      significantly with total WBC count (r = 0.194, P = 0.014). CONCLUSIONS: Because
      leukocytes are activated and secrete cytokines in the diabetic state and leptin
      stimulates leukocyte proliferation and differentiation, our results suggest that
      circulating leukocytes contribute to the development and progression of
      nephropathy, partially through the effects of leptin, in patients with type 2
      diabetes.

PMID- 15983325
TI  - Prospective study of lipoprotein(a) as a risk factor for deteriorating renal
      function in type 2 diabetic patients with overt proteinuria.
AB  - OBJECTIVE: The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic
      nephropathy has not been evaluated yet. The aim of this study was to determine
      whether Lp(a) is an independent risk factor for deteriorating renal function in
      type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS: We
      conducted this prospective study in type 2 diabetic patients with overt
      proteinuria. Patients were divided into two groups according to their baseline
      serum Lp(a) level. Group 1 had Lp(a) levels < or =30 mg/dl (n = 40) and group 2
      had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years.
      Progression of diabetic nephropathy was defined as a greater than twofold
      increase of follow-up serum creatinine concentration from the baseline value.
      RESULTS: At baseline and during the follow-up, there was no difference in HbA(1c)
      and lipid profile between groups 1 and 2. However, serum creatinine was
      significantly higher in group 2 than in group 1 after 1 year (148.3 +/- 78.0 vs.
      108.1 +/- 34.9 micromol/l, P = 0.004) and after 2 years (216.9 +/- 144.5 vs.
      131.3 +/- 47.3 micromol/l, P = 0.001), although baseline serum creatinine did not
      differ significantly between groups. In all, 13 of 14 patients with progression
      of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels
      were higher in the progressors than in the nonprogressors (62.9 +/- 26.7 vs. 33.5
      +/- 27.5 mg/dl, P < 0.001). Multiple logistic regression showed that baseline
      Lp(a) level was a significant and independent predictor of the progression of
      diabetic nephropathy. CONCLUSIONS: Our study demonstrated that Lp(a) is an
      independent risk factor for the progression of diabetic nephropathy in type 2
      diabetic patients with overt proteinuria.

PMID- 15983326
TI  - Urinary albumin excretion rate is associated with increased ambulatory blood
      pressure in normoalbuminuric type 2 diabetic patients.
AB  - OBJECTIVE: To evaluate the 24-h blood pressure profile in normoalbuminuric type 2
      diabetic patients. RESEARCH DESIGN AND METHODS: A cross-sectional study was
      conducted in 90 type 2 diabetic patients with a urinary albumin excretion rate
      (UAER) <20 microg/min on two occasions, 6 months apart (immunoturbidimetry).
      Patients underwent clinical and laboratory evaluations. Ambulatory blood pressure
      monitoring and echocardiograms were also performed. RESULTS: UAER was found to
      correlate positively with systolic doctor's office blood pressure measurements (r
      = 0.243, P = 0.021) and ambulatory blood pressure (24 h: r = 0.280, P = 0.008)
      and left ventricular posterior wall thickness (r = 0.359, P = 0.010). Patients
      were divided into four groups according to UAER (<5, > or =5-10, > or =10-15, and
      > or =15-20 microg/min). Systolic blood pressure parameters for the 1st, 2nd,
      3rd, and 4th groups, respectively, were 123.0 +/- 10.6, 132.5 +/- 15.0, 139.0 +/-
      23.4, and 130.7 +/- 8.0 mmHg for 24-h blood pressure (ANOVA P = 0.004) and 48.4
      +/- 6.0, 54.5 +/- 11.2, 58.8 +/- 15.6, and 57.6 +/- 8.0 mmHg for 24-h pulse
      pressure (ANOVA P = 0.003). A progressive increase in the prevalence of diabetic
      retinopathy was observed from the 1st to the 4th UAER group: 27.3, 43.8, 45.5,
      and 66.7% (P = 0.029 for trend). CONCLUSIONS: In type 2 diabetic patients, UAER
      in the normoalbuminuric range is positively associated with systolic ambulatory
      blood pressure indexes, left ventricular posterior wall thickness, and diabetic
      retinopathy, suggesting that intensive blood pressure treatment may prevent
      diabetes complications in these patients.

PMID- 15983327
TI  - Urinary incontinence and diabetes in postmenopausal women.
AB  - OBJECTIVE: This study evaluates diabetes characteristics and other risk factors
      for urinary incontinence among community-dwelling postmenopausal women. RESEARCH
      DESIGN AND METHODS: We performed a cross-sectional analysis of a population-based
      study of 1,017 postmenopausal women (218 with diabetes), aged 55-75 years,
      enrolled from a health maintenance organization. Outcomes included any
      incontinence and severe incontinence in the prior month. RESULTS: Overall, 60% of
      women had any incontinence in the prior month and 8% had severe incontinence.
      Parity and postvoid residual bladder volume were not associated with
      incontinence. Oral estrogen and vaginal estrogen use were positively associated
      with a report of any incontinence but not severe incontinence. A history of
      urinary tract infection (UTI) and measures of general health were associated with
      both outcomes. Women with diabetes reported disproportionately more severe
      incontinence, difficulty controlling urination, mixed (stress and urge)
      incontinence, use of pads, inability to completely empty the bladder, being
      unaware of leakage, and discomfort with urination (P < or = 0.06). Diabetes
      duration, treatment type, peripheral neuropathy, and retinopathy were
      significantly associated with severe incontinence in multiple regression models
      adjusted for age, education, and history of UTI (P = 0.01-0.06); however,
      additional adjustment for BMI diminished the strength of association (P = 0.17
      0.52). CONCLUSIONS: Urinary incontinence is highly prevalent among postmenopausal
      women. Women with diabetes are more likely to experience severe and symptomatic
      urinary incontinence. UTI history is a major risk factor, postvoid residual
      bladder volume plays no demonstrable role, and BMI confounds the relationship
      between diabetes and incontinence among healthy postmenopausal women.

PMID- 15983328
TI  - Clinical, socioeconomic, and lifestyle parameters associated with erectile
      dysfunction among diabetic men.
AB  - OBJECTIVE: Erectile dysfunction is frequently observed in diabetes. The current
      study aims to assess the association of a comprehensive set of clinical,
      socioeconomic, and lifestyle parameters with erectile dysfunction in diabetic
      men. RESEARCH DESIGN AND METHODS: Participants were randomly selected from male
      patients (age >18 years) treated in 26 diabetes clinics in Israel. Participants
      completed a self-reported questionnaire on demographic, socioeconomic, and
      lifestyle characteristics and on erectile function, using the IIEF-15
      (International Index of Erectile Function). Information on diabetes type,
      duration, treatment, and control; microvascular complications and cardiovascular
      disease; drug therapy; blood pressure; and lipid levels was also obtained.
      RESULTS: Information on erectile function was obtained in 1,040 patients. Their
      mean age was 57 years, and their median diabetes duration was 8 years (range <1
      50). Normal erectile function was found in 13.5% of the patients and severe
      erectile dysfunction in 30.1%. The characteristics found to be significantly
      associated with erectile dysfunction [associations presented as adjusted odds
      ratio (95% CI)] were: patient's age (5-year increments): 1.38 (1.29-1.48);
      diabetes duration (5-year increments): 1.16 (1.07-1.26); current HbA(1c) level
      (1% increment): 1.10 (1.01-1.19); any microvascular disease: 1.43 (1.09-1.88);
      cardiovascular disease: 1.78 (1.27-2.48); and diuretic treatment: 1.78 (1.09
      2.91). Leisure time and work-related physical activity and consumption of small
      amounts of alcohol were found to be protective: 0.51 (0.36-0.72) and 0.70 (0.51
      0.97), respectively. CONCLUSIONS: In diabetic men, erectile dysfunction severity
      increases with age and diabetes duration, poor glycemic control, presence of
      microvascular complications, diuretic treatment, and cardiovascular disease.
      Physical activity and alcohol intake may be protective. These findings can guide
      clinicians in taking preventive measures and undertaking early screening and
      treatment in high-risk patients.

PMID- 15983329
TI  - Birth weight and parental BMI predict overweight in children from mothers with
      gestational diabetes.
AB  - OBJECTIVE: To investigate the growth of children from pregnancies with
      gestational diabetes mellitus (GDM) and its association with antenatal maternal,
      fetal, and recent anthropometric parameters of mother and father. RESEARCH DESIGN
      AND METHODS: In 324 pregnancies of Caucasian women with GDM, BMI before
      pregnancy, maternal glycemic values, and measurements of the fetal abdominal
      circumference were recorded. The weight and height of infants were measured at
      birth and at follow-up at 5.4 years (range 2.5-8.5). In addition, somatic data
      from routine examinations at 6, 12, and 24 months and the BMI of parents at
      follow-up were obtained. BMI standard deviation scores (SDSs) were calculated
      based on age-correspondent data. RESULTS: At all time points, BMI was
      significantly above average (+0.82 SDS at birth; +0.56 at 6, +0.35 at 12, and
      +0.32 at 24 months; and +0.66 at follow-up; P < 0.001). BMI at birth was related
      to BMI at follow-up (r = 0.27, P < 0.001). The rate of overweight at follow-up
      was 37% in children with birth BMI > or =90th percentile and 25% in those with
      normal BMI at birth (P < 0.05). Abdominal circumference of third trimester and
      postprandial glucose values were related to BMI at follow-up (r = 0.22 and r =
      0.18, P < 0.01). Recent maternal, paternal, and birth BMI were independent
      predictors of BMI at follow-up (r = 0.42, P < 0.001). Sixty-nine percent of
      children of parents with BMI > or =30 kg/m(2) were overweight at follow-up
      compared with 20% of those with parental BMI <30 kg/m(2) (P < 0.001).
      CONCLUSIONS: Children of mothers with GDM have a high rate of overweight that is
      associated both with intrauterine growth and parental obesity.

PMID- 15983330
TI  - Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in
      hepatocyte nuclear factor-1alpha mutation carriers.
AB  - OBJECTIVE: Patients with diabetes due to hepatocyte nuclear factor (HNF)-1alpha
      mutations have beta-cell deficiency, insulin sensitivity, altered proinsulin
      levels, and a low renal threshold for glucose. It is uncertain how many of these
      features precede the development of diabetes. The aim of our study was to test
      for these characteristics in young nondiabetic HNF-1alpha mutation carriers.
      RESEARCH DESIGN AND METHODS: A total of 47 offspring from 19 extended families
      underwent genetic testing, a standard oral glucose tolerance test, and urine
      testing. RESULTS: HNF-1alpha mutations were found in 20 offspring, 7 with
      diabetes and 13 without diabetes. The 13 nondiabetic mutation carriers were
      compared with 27 family control subjects, who were matched for age, sex, and BMI.
      There was marked beta-cell deficiency with reduced insulinogenic index (53.5
      [31.5-90.9] vs. 226.0 [126.0-407.1], SD [range], P < 0.001) and area under the
      curve for insulin (P < 0.001). Insulin sensitivity was increased in mutation
      carriers (homeostatic model assessment of insulin sensitivity 144.6 [82.7-252.7]
      vs. 100 [66.9-149.4], P = 0.025). A total of 38% of mutation carriers had
      glycosuria at 2 h compared with 0% of control subjects (P = 0.0034). Those with
      glycosuria had peak glucose values that were higher than the mutations carriers
      without glycosuria (range 8.1-11.8 vs. 6.2-8.4 mmol/l, P = 0.002). The seven
      subjects with diabetes all showed glycosuria. CONCLUSIONS: We conclude that
      marked beta-cell deficiency, increased insulin sensitivity, and a low renal
      threshold are present in young nondiabetic HNF-1alpha mutation carriers. The
      presence of glycosuria post-glucose load could be used to screen children of
      mutation carriers as it occurs in all mutation carriers with a peak glucose in
      the oral glucose tolerance test >8.4 mmol/l.

PMID- 15983331
TI  - Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City
      diabetes study.
AB  - OBJECTIVE: To test the hypothesis that enzymes conventionally associated with
      liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma
      glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes.
      RESEARCH DESIGN AND METHODS: From a population-based diabetes survey, we selected
      1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean
      population value, alcohol intake was <250 g/week, and hepatitis B and C virus
      testing was negative. At follow-up (7 years), 94 subjects developed diabetes and
      93 impaired glucose tolerance (IGT). RESULTS: At baseline, all four enzymes were
      related to most of the features of the metabolic syndrome. After controlling for
      sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood
      pressure, higher alanine aminotransferase and GGT values were significantly (P <
      0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was
      associated with diabetes only (P = 0.0004) and aspartate aminotransferase with
      IGT only (P = 0.0001). Raised GGT alone was associated with all the features of
      the metabolic syndrome. Raised GGT was a significant predictor of either IGT or
      diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P
      < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol
      consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose
      plasma glucose concentrations. CONCLUSIONS: Although mild elevations in liver
      enzymes are associated with features of the metabolic syndrome, only raised GGT
      is an independent predictor of deterioration of glucose tolerance to IGT or
      diabetes. As GGT signals oxidative stress, the association with diabetes may
      reflect both hepatic steatosis and enhanced oxidative stress.

PMID- 15983332
TI  - Relation of C-reactive protein to insulin resistance and cardiovascular risk
      factors in youth.
AB  - OBJECTIVE: Insulin resistance and C-reactive protein (CRP) levels are strongly
      correlated in adults. This study explored the relationship in youth. RESEARCH
      DESIGN AND METHODS: Associations between CRP levels, cardiovascular risk, and
      insulin resistance measured by the euglycemic clamp were investigated in 342
      healthy Minneapolis youth. RESULTS: There was no difference in mean CRP levels
      among boys (n = 189, CRP 1.10 +/- 0.46 mg/l) and girls (n = 153, CRP 1.16 +/-
      0.63 mg/l; P = 0.32). There was also no difference between CRP and Tanner stage.
      CRP, adjusted for BMI, was significantly greater in black subjects compared with
      white subjects (P = 0.03). CRP was strongly related to adiposity in both girls
      and boys. CRP levels were related to fasting insulin levels (r = 0.16, P = 0.003)
      but this association was not significant after adjustment for BMI (r = 0.07, P =
      0.21). Similarly, M, the euglycemic clamp measurement of insulin sensitivity, was
      significantly related to CRP levels (r = -0.13, P = 0.02) but not when M was
      normalized to lean body mass (M(lbm)) (r = -0.10, P = 0.09). There was a
      significant inverse correlation between M(lbm) and CRP quartiles, which
      disappeared after adjustment for BMI. There was no significant association
      between CRP levels and lipids, blood pressure, physical activity, or left
      ventricular mass. CONCLUSIONS: In contrast to adult subjects, after adjustment
      for adiposity, CRP levels in children age 10-16 years were not significantly
      associated with insulin resistance or with other factors comprising the metabolic
      syndrome. This is consistent with the concept that insulin resistance may precede
      the development of CRP elevation in the evolution of the metabolic syndrome.

PMID- 15983333
TI  - Risks for all-cause mortality, cardiovascular disease, and diabetes associated
      with the metabolic syndrome: a summary of the evidence.
AB  - OBJECTIVE: In recent years, several major organizations have endorsed the concept
      of the metabolic syndrome and developed working definitions for it. How well
      these definitions predict the risk for adverse events in people with the
      metabolic syndrome is only now being learned. The purpose of this study was to
      summarize the estimates of relative risk for all-cause mortality, cardiovascular
      disease, and diabetes reported from prospective studies in samples from the
      general population using definitions of the metabolic syndrome developed by the
      National Cholesterol Education Program (NCEP) and World Health Organization
      (WHO). RESEARCH DESIGN AND METHODS: The author reviewed prospective studies from
      July 1998 through August 2004. RESULTS: For studies that used the exact NCEP
      definition of the metabolic syndrome, random-effects estimates of combined
      relative risk were 1.27 (95% CI 0.90-1.78) for all-cause mortality, 1.65 (1.38
      1.99) for cardiovascular disease, and 2.99 (1.96-4.57) for diabetes. For studies
      that used the most exact WHO definition of the metabolic syndrome, the fixed
      effects estimates of relative risk were 1.37 (1.09-1.74) for all-cause mortality
      and 1.93 (1.39-2.67) for cardiovascular disease; the fixed-effects estimate was
      2.60 (1.55-4.38) for coronary heart disease. CONCLUSIONS: These estimates suggest
      that the population-attributable fraction for the metabolic syndrome, as it is
      currently conceived, is approximately 6-7% for all-cause mortality, 12-17% for
      cardiovascular disease, and 30-52% for diabetes. Further research is needed to
      establish the use of the metabolic syndrome in predicting risk for death,
      cardiovascular disease, and diabetes in various population subgroups.

PMID- 15983334
TI  - Dietary fat is associated with metabolic syndrome in Japanese Brazilians.
AB  - OBJECTIVE: The aim of this study was to examine the association of nutrient
      intakes with metabolic syndrome in a Japanese descendant population at high risk
      for metabolic abnormalities. RESEARCH DESIGN AND METHODS: In a population-based
      study of Japanese Brazilians aged > or =30 years, 412 men and 465 women were
      studied. The diagnosis of metabolic syndrome was based on the National
      Cholesterol Education Program criteria modified for Asians. Food intake was
      assessed by a validated food frequency questionnaire. RESULTS: Men and women
      showed similar mean ages (55.7 +/- 12.7 and 54.4 +/- 11.9 years) and 49% (95% CI
      44.8-54.6) and 43% (38.4-47.6) had metabolic syndrome, respectively. As expected,
      clinical parameters were less favorable in the subset of subjects with metabolic
      syndrome. Men with metabolic syndrome showed higher cholesterol (233.2 +/- 116.3
      vs. 211.7 +/- 5.8 g/day, P < 0.05) and lower carbohydrate (288.5 +/- 45.8 vs.
      300.1 +/- 39.8 g/day, P < 0.001) intakes than those without metabolic syndrome,
      but no difference was observed among the women. After adjusting for sex, age,
      smoking, education level, generation, physical activity, total energy, and
      dietary fiber intake, a positive association between metabolic syndrome and total
      fat intake was detected. Comparing people in the highest quintile of total fat
      consumption with those in the lowest quintile, odds ratio (OR) of metabolic
      syndrome was 5.0 ([95% CI 1.58-16.00]; P < 0.005). In contrast, linoleic acid
      intake was inversely associated with metabolic syndrome (OR 0.50 [95% CI 0.26
      0.98]; P < 0.05). Considering food groups, after adjustments only fried food
      intake was shown to be associated with increased risk of metabolic syndrome.
      CONCLUSIONS: Despite the limitation of such a study design in investigating cause
      effect relationships, our findings favor the hypothesis that dietary total fat
      may increase whereas linoleic acid intake may reduce the risk of metabolic
      syndrome in Japanese descendants living in Brazil.

PMID- 15983335
TI  - Changing the definition of impaired fasting glucose: impact on the classification
      of individuals and risk definition.
AB  - OBJECTIVE: This study evaluates the impact of lowering the diagnostic threshold
      for impaired fasting glucose (IFG) from 6.1 to 5.6 mmol/l as proposed by the
      American Diabetes Association (ADA) on the prevalence of the condition,
      classification of individuals, and risk definition. RESEARCH DESIGN AND METHODS:
      A total of 1,285 employees of the Italian Telephone Company aged 35-59 years
      without known diabetes underwent an oral glucose tolerance test (OGTT). BMI,
      serum cholesterol, triglycerides, and blood pressure were measured. Medication
      use was recorded. RESULTS: With the new ADA criterion, the proportion of people
      diagnosed with IFG increased from 3.2 to 9.7%. The newly proposed IFG category
      identified 41% of all subjects with impaired glucose tolerance (IGT) compared
      with 16.2% identified with the use of the World Health Organization criterion for
      IFG; the improvement in accuracy has been achieved at the cost of classifying
      more previously "normal" subjects as having IFG (from 2.3 to 7.3%). Both IFG and
      IGT were associated with an unfavorable risk profile for diabetes and
      cardiovascular disease, with a higher estimated risk for IGT than IFG.
      CONCLUSIONS: Even with the revised diagnostic criterion, IFG and IGT identify
      distinct groups that have a different background risk. The cost/benefit of
      preventive measures tested in people with IGT may not apply to the new IFG
      category.

PMID- 15983336
TI  - Repaglinide/bedtime NPH insulin is comparable to twice-daily NPH insulin.

PMID- 15983338
TI  - Identification of patients with diabetes from the text of physician notes in the
      electronic medical record.

PMID- 15983337
TI  - Psychological characteristics of frequent short-notice cancellers of diabetes
      medical and education appointments.

PMID- 15983339
TI  - Non-HDL cholesterol is less informative than the total-to-HDL cholesterol ratio
      in predicting cardiovascular risk in type 2 diabetes.

PMID- 15983340
TI  - Triglyceride-to-HDL cholesterol ratio in the dyslipidemic classification of type
      2 diabetes.

PMID- 15983341
TI  - Day after the night before: influence of evening alcohol on risk of hypoglycemia
      in patients with type 1 diabetes.

PMID- 15983342
TI  - Comparison of clinical and laboratory characteristics between adult-onset type 1
      diabetes and latent autoimmune diabetes in adults.

PMID- 15983343
TI  - Diabetes and colorectal cancer incidence in the cohort of Swedish men.

PMID- 15983344
TI  - Rarer than a blue moon: the use of a diagnostic code for the metabolic syndrome
      in the U.S.

PMID- 15983345
TI  - Changes in the characteristics of metabolic syndrome in Korea over the period
      1998-2001 as determined by Korean National Health and Nutrition Examination
      Surveys.

PMID- 15983346
TI  - Screening for kidney disease in adults with diabetes.

PMID- 15983347
TI  - Is it ethical to assign medically underserved African Americans to a usual-care
      control group in community-based intervention research?

PMID- 15983348
TI  - Second World Congress on the Insulin Resistance Syndrome: mediators, pediatric
      insulin resistance, the polycystic ovary syndrome, and malignancy.

PMID- 15983349
TI  - Metabolic syndrome: underrated or underdiagnosed?

PMID- 15983350
TI  - C-reactive protein for cardiovascular risk assessment.

PMID- 15983351
TI  - Critical evaluation of models to identify individuals with insulin resistance.

PMID- 15983352
TI  - Age and A1C are important clinical predictors of continuous subcutaneous insulin
      infusion efficacy in type 1 diabetic patients.

PMID- 15983353
TI  - Continuous subcutaneous insulin infusion versus multiple daily injections:
      modeling predicted benefits in relationship to baseline A1c.

PMID- 15983354
TI  - The effect of blood sample volume on 11 glucose monitoring systems.

PMID- 15983355
TI  - Anticraving effects of topiramate in a diabetic patient.

PMID- 15983357
TI  - Diabetes is the main factor accounting for the high ferritin levels detected in
      chronic hepatitis C virus infection: response to Lecube et al.

PMID- 15983358
TI  - Glycemic index, glycemic load, and glycemic response are not the same.

PMID- 15983359
TI  - Alpha-glucosidase inhibitors for patients with type 2 diabetes: response to van
      de Laar et al.

PMID- 15983360
TI  - Chromium supplementation does not improve glucose tolerance, insulin sensitivity,
      or lipid profile: a randomized, placebo-controlled, double-blind trial of
      supplementation in subjects with impaired glucose tolerance: response to Gunton
      et al.

PMID- 15983363
TI  - The case for biennial retinopathy screening in children and adolescents: response
      to Maguire et al.

PMID- 15983365
TI  - Downregulation of NANOG induces differentiation of human embryonic stem cells to
      extraembryonic lineages.
AB  - The homeobox transcription factor Nanog has been proposed to play a crucial role
      in the maintenance of the undifferentiated state of murine embryonic stem cells.
      A human counterpart, NANOG, has been identified, but its function and
      localization have not hitherto been described. We have used a combination of RNA
      interference and quantitative real-time polymerase chain reaction to study NANOG
      in human embryonic stem and embryonic carcinoma cells. Transfection of NANOG
      specific small interfering RNAs reduced levels of NANOG transcript and protein
      and induced activation of the extraembryonic endoderm-associated genes GATA4,
      GATA6, LAMININ B1, and AFP as well as upregulation of trophectoderm-associated
      genes CDX2, GATA2, hCG-alpha, and hCG-beta. Immunostaining of preimplantation
      human embryos showed that NANOG was expressed in the inner cell mass of expanded
      blastocysts but not in earlier-stage embryos, consistent with a role in the
      maintenance of pluripotency. Taken together, our findings suggest that NANOG acts
      as a gatekeeper of pluripotency in human embryonic stem and carcinoma cells by
      preventing their differentiation to extraembryonic endoderm and trophectoderm
      lineages.

PMID- 15983366
TI  - Differential induction of IgE-mediated anaphylaxis after soluble vs. cell-bound
      tolerogenic peptide therapy of autoimmune encephalomyelitis.
AB  - The ability of different forms of myelin peptides to induce tolerance for the
      treatment of preestablished murine experimental autoimmune encephalomyelitis
      (EAE), a mouse model of multiple sclerosis, was evaluated. i.v. administration of
      myelin peptide-pulsed, ethylene carbodiimide-fixed syngeneic splenocytes, but not
      soluble myelin peptide monomers or oligomers, proved exceedingly effective at
      treating preestablished EAE, resulting in amelioration of disease progression. In
      addition to the lack of therapeutic efficacy of soluble peptide and peptide
      oligomer, administering them i.v. after the onset of clinical symptoms in many
      but not all peptide-induced EAE models led to a rapid-onset anaphylactic reaction
      characterized by respiratory distress, erythema, decreased body temperature,
      unresponsiveness, and, often, death. By using anti-IgE antibody treatments and
      mice with targeted mutations of the FcgammaRIII alpha-chain or the common gamma
      chain of FcepsilonRI and FcgammaRI/III, we demonstrate that IgE crosslinking of
      FcepsilonRI appears to be necessary and sufficient for myelin peptide-induced
      anaphylaxis. The implications of these findings to myelin peptide/protein
      tolerance strategies for the treatment of multiple sclerosis are discussed.

PMID- 15983367
TI  - Early experience affects the intergenerational transmission of infant abuse in
      rhesus monkeys.
AB  - Maternal abuse of offspring in macaque monkeys shares some similarities with
      child maltreatment in humans, including its transmission across generations. This
      study used a longitudinal design and a cross-fostering experiment to investigate
      whether abusive parenting in rhesus macaques is transmitted from mothers to
      daughters and whether transmission occurs through genetic or experiential
      factors. Nine of 16 females who were abused by their mothers in their first month
      of life, regardless of whether they were reared by their biological mothers or by
      foster mothers, exhibited abusive parenting with their firstborn offspring,
      whereas none of the females reared by nonabusive mothers did. These results
      suggest that the intergenerational transmission of infant abuse in rhesus monkeys
      is the result of early experience and not genetic inheritance. The extent to
      which the effects of early experience on the intergenerational transmission of
      abusive parenting are mediated by social learning or experience-induced
      physiological alterations remains to be established.

PMID- 15983369
TI  - Profile of Bruce D. Smith.

PMID- 15983368
TI  - Cardiac glycosides inhibit TNF-alpha/NF-kappaB signaling by blocking recruitment
      of TNF receptor-associated death domain to the TNF receptor.
AB  - Digitoxin and structurally related cardiac glycoside drugs potently block
      activation of the TNF-alpha/NF-kappaB signaling pathway. We have hypothesized
      that the mechanism might be discovered by searching systematically for selective
      inhibitory action through the entire pathway. We report that the common action of
      these drugs is to block the TNF-alpha-dependent binding of TNF receptor 1 to TNF
      receptor-associated death domain. This drug action can be observed with native
      cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All
      other antiinflammatory effects of digitoxin on NF-kappaB and c-Jun N-terminal
      kinase pathways appear to follow from the blockade of this initial upstream
      signaling event.

PMID- 15983370
TI  - Neuropeptide B-deficient mice demonstrate hyperalgesia in response to
      inflammatory pain.
AB  - Neuropeptide B (NPB) and neuropeptide W (NPW) have been recently identified as
      ligands for the G protein-coupled receptor (GPR) 7 and GPR8. The precise in vivo
      role of this neuropeptide-receptor pathway has not been fully demonstrated. In
      this paper, we report that NPB-deficient mice manifest a mild adult-onset
      obesity, similar to that reported in GPR7-null mice. NPB-deficient mice also
      exhibit hyperalgesia in response to inflammatory pain. Hyperalgesia was not
      observed in response to chemical pain, thermal pain, or electrical stimulation.
      NPB-deficient mice demonstrated intact behavioral responses to pain, and learning
      from the negative reinforcement of electrical stimulation was unaltered. Baseline
      anxiety was also unchanged as measured in both the elevated plus maze and time
      spent immobile in a novel environment. These data support the idea that NPB is a
      factor in the modulation of responses to inflammatory pain and body weight
      homeostasis.

PMID- 15983371
TI  - Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene.
AB  - Neurobiology of speech and language has previously been studied in the KE family,
      in which half of the members have severe impairment in both speech and language.
      The gene responsible for the phenotype was mapped to chromosome 7q31 and
      identified as the FOXP2 gene, coding for a transcription factor containing a
      polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies
      implicating 7q31 in autism, where language impairment is a component of the
      disorder, and in specific language impairment, FOXP2 has also been considered as
      a potential susceptibility locus for the language deficits in autism and/or
      specific language impairment. In this study, we characterized mice with a
      disruption in the murine Foxp2 gene. Disruption of both copies of the Foxp2 gene
      caused severe motor impairment, premature death, and an absence of ultrasonic
      vocalizations that are elicited when pups are removed from their mothers.
      Disruption of a single copy of the gene led to modest developmental delay but a
      significant alteration in ultrasonic vocalization in response to such separation.
      Learning and memory appear normal in the heterozygous animals. Cerebellar
      abnormalities were observed in mice with disruptions in Foxp2, with Purkinje
      cells particularly affected. Our findings support a role for Foxp2 in cerebellar
      development and in a developmental process that subsumes social communication
      functions in diverse organisms.

PMID- 15983372
TI  - Origin of the Eumetazoa: testing ecological predictions of molecular clocks
      against the Proterozoic fossil record.
AB  - Molecular clocks have the potential to shed light on the timing of early metazoan
      divergences, but differing algorithms and calibration points yield conspicuously
      discordant results. We argue here that competing molecular clock hypotheses
      should be testable in the fossil record, on the principle that fundamentally new
      grades of animal organization will have ecosystem-wide impacts. Using a set of
      seven nuclear-encoded protein sequences, we demonstrate the paraphyly of Porifera
      and calculate sponge/eumetazoan and cnidarian/bilaterian divergence times by
      using both distance [minimum evolution (ME)] and maximum likelihood (ML)
      molecular clocks; ME brackets the appearance of Eumetazoa between 634 and 604 Ma,
      whereas ML suggests it was between 867 and 748 Ma. Significantly, the ME, but not
      the ML, estimate is coincident with a major regime change in the Proterozoic
      acritarch record, including: (i) disappearance of low-diversity, evolutionarily
      static, pre-Ediacaran acanthomorphs; (ii) radiation of the high-diversity, short
      lived Doushantuo-Pertatataka microbiota; and (iii) an order-of-magnitude increase
      in evolutionary turnover rate. We interpret this turnover as a consequence of the
      novel ecological challenges accompanying the evolution of the eumetazoan nervous
      system and gut. Thus, the more readily preserved microfossil record provides
      positive evidence for the absence of pre-Ediacaran eumetazoans and strongly
      supports the veracity, and therefore more general application, of the ME
      molecular clock.

PMID- 15983373
TI  - Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary
      factor (TIF) 2 in androgen receptor activity in mice.
AB  - Genetic disruption of the steroid receptor coactivator (SRC)-1 and
      transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive
      mutant phenotypes. To quantify their roles in the function of androgen receptor
      (AR) transcriptional activity in vivo, we generated a unique transgenic AR
      reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to
      the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR
      lacZ mice harbor a recombinant mouse AR gene, AR(GAL4DBD), which is functionally
      coupled with a upstream activation sequence-mediated reporter gene (AR activity
      indicator). After characterization of these mice in terms of AR function, we
      further derived bigenic mice by crossing AR activity indicator mice with the SRC
      1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo
      imaging and luciferase assays showed that testicular AR activity was decreased
      significantly in those with the TIF2+/- mutation but not in the SRC-1+/-
      background, suggesting that TIF2 serves as the preferential coactivator for AR in
      testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse
      testicular Sertoli cell nuclei under normal conditions. Although SRC-1
      concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not
      able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1
      appears to negatively influence AR activity, thereby counterbalancing the TIF2
      stimulated AR activity. Our results provide unique in vivo insights to the
      multidimensional cell-type-specific interactions between AR and coregulators.

PMID- 15983374
TI  - Silencing the expression of multiple Gbeta-subunits eliminates signaling mediated
      by all four families of G proteins.
AB  - The Gbetagamma-subunit complex derived from heterotrimeric G proteins can act to
      regulate the function of a variety of protein targets. We established lentiviral
      based RNA interference in J774A.1 mouse macrophages to characterize the role of
      Gbeta in G protein-coupled receptor signaling. The expression of Gbeta1 and
      Gbeta2, the major subtypes present in J774A.1 cells, was eliminated by sequential
      treatment with small hairpin RNA expressing lentivirus. These betagamma complex
      deficient cells lost the ability to respond to G protein-mediated signals.
      Chemotaxis and the phosphorylation of Akt in response to C5a were both blocked.
      Similarly, C5a-mediated actin polymerization, C5a- and UTP-stimulated
      intracellular calcium mobilization, and the stimulation of cAMP formation by
      isoproterenol were all eliminated in the absence of the Gbeta-subunits. In
      addition, stabilization and membrane localization of several Galpha- and Ggamma
      subunit proteins was strongly effected. Furthermore, in DNA microarray analysis,
      regulation of gene expression stimulated by prostaglandin E2 and UTP was not
      observed in cells lacking Gbeta-subunits. In contrast, phagocytotic activity,
      serum-dependent cell growth and the patterns of gene expression induced by
      stimulating the Toll receptors with LPS were similar in wild-type cells and small
      hairpin RNA-containing cells. Thus, ablation of the Gbeta-subunits destabilized
      Galpha- and Ggamma-subunits and effectively eliminated G protein-mediated
      signaling responses. Unrelated ligand regulated pathways remained intact. These
      cells provide a system that can be used to study signaling in the absence of most
      G protein-mediated functions.

PMID- 15983375
TI  - Isolation and functional expression of an animal geranyl diphosphate synthase and
      its role in bark beetle pheromone biosynthesis.
AB  - Geranyl diphosphate synthase (GPPS) catalyzes the condensation of dimethylallyl
      diphosphate and isopentenyl diphosphate to form geranyl diphosphate. Geranyl
      diphosphate is the precursor of monoterpenes, a large family of natural occurring
      C(10) compounds predominantly found in plants. Similar to plants but unique to
      animals, some bark beetle genera (Coleoptera: Scolytidae) produce monoterpenes
      that function in intraspecific chemical communication as aggregation and
      dispersion pheromones. The release of monoterpene aggregation pheromone mediates
      host colonization and mating. It has been debated whether these monoterpene
      pheromone components are derived de novo through the mevalonate pathway or result
      from simple modifications of dietary precursors. The data reported here provide
      conclusive evidence for de novo biosynthesis of monoterpene pheromone components
      from bark beetles. We describe GPPS in the midgut tissue of pheromone-producing
      male Ips pini. GPPS expression levels are regulated by juvenile hormone III,
      similar to other mevalonate pathway genes involved in pheromone biosynthesis. In
      addition, GPPS transcript is almost exclusively expressed in the anterior midgut
      of male I. pini, the site of aggregation pheromone biosynthesis. The recombinant
      enzyme was functionally expressed and produced geranyl diphosphate as its major
      product. The three-dimensional model structure of GPPS shows that the insect
      enzyme has the sequence structural motifs common to E-isoprenyl diphosphate
      synthases.

PMID- 15983376
TI  - Protein identification using sequential ion/ion reactions and tandem mass
      spectrometry.
AB  - A method for rapid sequencing of intact proteins simultaneously from the N and C
      termini (1-2 s) with online chromatography is described and applied to the
      characterization of histone H3.1 posttranslational modifications and the
      identification of an additional member of the H2A gene family. Proteins are
      converted to gas-phase multiply charged positive ions by electrospray ionization
      and then allowed to react with fluoranthene radical anions. Electron transfer to
      the multiply charged protein promotes random dissociation of the N-Calpha bonds
      of the protein backbone. Multiply charged fragment ions are then deprotonated in
      a second ion/ion reaction with the carboxylate anion of benzoic acid. The m/z
      values for the resulting singly and doubly charged ions are used to read a
      sequence of 15-40 aa at both the N and C termini of the protein. This
      information, with the measured mass of the intact protein, is used to search
      protein or nucleotide databases for possible matches, detect posttranslational
      modifications, and determine possible splice variants.

PMID- 15983377
TI  - Efficient synthetic inhibitors of anthrax lethal factor.
AB  - Inhalation anthrax is a deadly disease for which there is currently no effective
      treatment. Bacillus anthracis lethal factor (LF) metalloproteinase is an integral
      component of the tripartite anthrax lethal toxin that is essential for the onset
      and progression of anthrax. We report here on a fragment-based approach that
      allowed us to develop inhibitors of LF. The small-molecule inhibitors we have
      designed, synthesized, and tested are highly potent and selective against LF in
      both in vitro tests and cell-based assays. These inhibitors do not affect the
      prototype human metalloproteinases that are structurally similar to LF. Initial
      in vivo evaluation of postexposure efficacy of our inhibitors combined with
      antibiotic ciprofloxacin against B. anthracis resulted in significant protection.
      Our data strongly indicate that the scaffold of inhibitors we have identified is
      the foundation for the development of novel, safe, and effective emergency
      therapy of postexposure inhalation anthrax.

PMID- 15983378
TI  - Sampling motifs on phylogenetic trees.
AB  - We present a method to find motifs by simultaneously using the overrepresentation
      property and the evolutionary conservation property of motifs. This method is
      applicable to divergent species where alignment is unreliable, which overcomes a
      major limitation of the current methods. The method has been applied to search
      regulatory motifs in four yeast species based on ChIP-chip data in Saccharomyces
      cerevisiae and obtained 20% higher accuracy than the best current methods. We
      also discovered cis-regulatory elements that govern the tight regulation of
      ribosomal protein genes in two distantly related insects by using this method.
      These results demonstrate that our method will be useful for the extraction of
      regulatory signals in multiple genomes.

PMID- 15983379
TI  - CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals
      in the immunological synapse.
AB  - Adenosine deaminase (ADA), a protein whose deficit leads to severe combined
      immunodeficiency, binds to the cell surface by means of either CD26, A(1)
      adenosine receptors, or A(2B) adenosine receptors. The physiological role of
      these interactions is not well understood. Our results show that by a 3-fold
      reduction in the EC(50) for the antigen, ADA potentiated T cell proliferation in
      autologous cocultures with antigen-pulsed immature or mature dendritic cells.
      Costimulation was not due to the enzymatic activity but to the interaction of ADA
      CD26 complexes in T cells with an ADA-anchoring protein in dendritic cells. From
      colocalization studies, it is deduced that ADA colocalizing with adenosine
      receptors on dendritic cells interact with CD26 expressed on lymphocytes. This
      costimulatory signal in the immunological synapse leads to a marked increase (3-
      to 34-fold) in the production of the T helper 1 and proimmflamatory cytokines IFN
      gamma, TNF-alpha, and IL-6.

PMID- 15983380
TI  - Complex humoral immune response against a benign tumor: frequent antibody
      response against specific antigens as diagnostic targets.
AB  - There are numerous studies on the immune response against malignant human tumors.
      This study was aimed to address the complexity and specificity of humoral immune
      response against a benign human tumor. We assembled a panel of 62 meningioma
      expressed antigens that show reactivity with serum antibodies of meningioma
      patients, including 41 previously uncharacterized antigens by screening of a
      fetal brain expression library. We tested the panel for reactivity with 48 sera,
      including sera of patients with common-type, atypical, and anaplastic meningioma,
      respectively. Meningioma sera detected an average of 14.6 antigens per serum and
      normal sera an average of 7.8 antigens per serum (P = 0.0001). We found a decline
      of seroreactivity with malignancy with a statistical significant difference
      between common-type and anaplastic meningioma (P < 0.05). We detected 17 antigens
      exclusively with patient sera, including 12 sera that were reactive against
      KIAA1344, 9 against natural killer tumor recognition (NKTR), and 7 against SRY
      (sex determining region Y)-box2 (SOX2). More than 80% of meningioma patients had
      antibodies against at least one of the antigens KIAA1344, SC65, SOX2, and
      C6orf153. Our results show a highly complex but specific humoral immune response
      against a benign tumor with a distinct serum reactivity pattern and a decline of
      complexity with malignancy. The frequent antibody response against specific
      antigens offers new diagnostic and therapeutic targets for meningioma. We
      developed a statistical learning method to differentiate sera of meningioma
      patients from sera of healthy donors.

PMID- 15983381
TI  - Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1
      activity and cell death.
AB  - Investigations into the cellular and molecular biology of genes that cause
      inherited forms of Parkinson's disease, as well as the downstream pathways that
      they trigger, shed considerable light on our understanding the fundamental
      determinants of life and death in dopaminergic neurons. Homozygous deletion or
      missense mutation in DJ-1 results in autosomal recessively inherited Parkinson's
      disease, suggesting that wild-type DJ-1 has a favorable role in maintaining these
      neurons. Here, we show that DJ-1 protects against oxidative stress-induced cell
      death, but that its relatively modest ability to quench reactive oxygen species
      is insufficient to account for its more robust cytoprotective effect. To
      elucidate the mechanism of this cell-preserving function, we have screened out
      the death protein Daxx as a DJ-1-interacting partner. We demonstrate that wild
      type DJ-1 sequesters Daxx in the nucleus, prevents it from gaining access to the
      cytoplasm, from binding to and activating its effector kinase apoptosis signal
      regulating kinase 1, and therefore, from triggering the ensuing death pathway.
      All these steps are impaired by the disease-causing L166P mutant isoform of DJ-1.
      These findings suggest that the regulated sequestration of Daxx in the nucleus
      and keeping apoptosis signal-regulating kinase 1 activation in check is a
      critical mechanism by which DJ-1 exerts its cytoprotective function.

PMID- 15983382
TI  - c-Myc induces chromosomal rearrangements through telomere and chromosome
      remodeling in the interphase nucleus.
AB  - In previous work, we showed that telomeres of normal cells are organized within
      the 3D space of the interphase nucleus in a nonoverlapping and cell cycle
      dependent manner. This order is distorted in tumor cell nuclei where telomeres
      are found in close association forming aggregates of various numbers and sizes.
      Here we show that c-Myc overexpression induces telomeric aggregations in the
      interphase nucleus. Directly proportional to the duration of c-Myc deregulation,
      we observe three or five cycles of telomeric aggregate formation in interphase
      nuclei. These cycles reflect the onset and propagation of breakage-bridge-fusion
      cycles that are initiated by end-to-end telomeric fusions of chromosomes.
      Subsequent to initial chromosomal breakages, new fusions follow and the breakage
      bridge-fusion cycles continue. During this time, nonreciprocal translocations are
      generated. c-Myc-dependent remodeling of the organization of telomeres thus
      precedes the onset of genomic instability and subsequently leads to chromosomal
      rearrangements. Our findings reveal that c-Myc possesses the ability to
      structurally modify chromosomes through telomeric fusions, thereby reorganizing
      the genetic information.

PMID- 15983383
TI  - Reversible molecular photoswitches: a key technology for nanoscience and
      fluorescence imaging.

PMID- 15983384
TI  - High-resolution genomic profiles of human lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality worldwide, yet there exists
      a limited view of the genetic lesions driving this disease. In this study, an
      integrated high-resolution survey of regional amplifications and deletions,
      coupled with gene-expression profiling of non-small-cell lung cancer subtypes,
      adenocarcinoma and squamous-cell carcinoma (SCC), identified 93 focal copy-number
      alterations, of which 21 span <0.5 megabases and contain a median of five genes.
      Whereas all known lung cancer genes/loci are contained in the dataset, most of
      these recurrent copy-number alterations are previously uncharacterized and
      include high-amplitude amplifications and homozygous deletions. Notably, despite
      their distinct histopathological phenotypes, adenocarcinoma and SCC genomic
      profiles showed a nearly complete overlap, with only one clear SCC-specific
      amplicon. Among the few genes residing within this amplicon and showing
      consistent overexpression in SCC is p63, a known regulator of squamous-cell
      differentiation. Furthermore, intersection with the published pancreatic cancer
      comparative genomic hybridization dataset yielded, among others, two focal
      amplicons on 8p12 and 20q11 common to both cancer types. Integrated DNA-RNA
      analyses identified WHSC1L1 and TPX2 as two candidates likely targeted for
      amplification in both pancreatic ductal adenocarcinoma and non-small-cell lung
      cancer.

PMID- 15983385
TI  - Graded bidirectional synaptic plasticity is composed of switch-like unitary
      events.
AB  - Biological information storage events are often rapid transitions between
      discrete states. In neural systems, the initiation of bidirectional plasticity by
      all-or-none events may help confer robustness on memory storage. Here, we report
      that at CA3-CA1 hippocampal synapses, individual potentiation and depression
      plasticity events are discrete and heterogeneous in nature. Individual synapses
      began from extreme high and low strength states. Unitary plasticity events were
      all-or-none and drove synaptic strength between extremes in <1 min. Under naive
      conditions, approximately three-fourths of synapses began in a low-strength
      state. The timing of these unitary events can account for the time course of
      macroscopic synaptic plasticity.

PMID- 15983386
TI  - Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal
      regeneration.
AB  - The p63 gene generates transactivating and N-terminally truncated transcripts
      (DeltaNp63) initiated by different promoters. Alternative splicing gives rise to
      three different C termini, designated alpha, beta, and gamma. In the ocular
      epithelium, the corneal stem cells, which are segregated in the basal layer of
      the limbus, contain the alpha isoform but not beta or gamma. Holoclones derived
      from the limbus are rich in alpha, meroclones contain little, and paraclones
      contain none. In normal resting corneal epithelium, p63 of all isoforms is
      absent. Upon corneal wounding, cells originating from the limbus and containing
      alpha migrate progressively through the epithelium of the peripheral and central
      cornea. In the absence of an attached limbus, no alpha isoform appears in the
      corneal epithelium. When migrating cells containing the alpha isoform appear in
      the wounded corneal epithelium, they are confined to the basal layer, but the
      suprabasal cells, not only of the cornea but of the limbus as well, contain mRNA
      encoding beta and gamma. These data support the concept that the alpha isoform of
      p63 is necessary for the maintenance of the proliferative potential of limbal
      stem cells and their ability to migrate over the cornea. The beta and gamma
      isoforms, being suprabasal and virtually absent from the resting limbus, are not
      stem cell markers but are likely to play a role in epithelial differentiation
      specifically during the process of corneal regeneration.

PMID- 15983388
TI  - Intracellular signal transduction pathway proteins as targets for cancer therapy.
AB  - Circulating cytokines, hormones, and growth factors control all aspects of cell
      proliferation, differentiation, angiogenesis, apoptosis, and senescence. These
      chemical signals are propagated from the cell surface to intracellular processes
      via sequential kinase signaling, arranged in modules that exhibit redundancy and
      cross talk. This signal transduction system comprising growth factors,
      transmembrane receptor proteins, and cytoplasmic secondary messengers is often
      exploited to optimize tumor growth and metastasis in malignancies. Thus, it
      represents an attractive target for cancer therapy. This review will summarize
      current knowledge of selected intracellular signaling networks and their role in
      cancer therapy. The focus will be on pathways for which inhibitory agents are
      currently undergoing clinical testing. Original data for inclusion in this review
      were identified through a MEDLINE search of the literature. All papers from 1966
      through March 2005 were identified by the following search terms: "signal
      transduction," "intracellular signaling," "kinases," "proliferation," "growth
      factors," and "cancer therapy." All original research and review papers related
      to the role of intracellular signaling in oncogenesis and therapeutic
      interventions relating to abnormal cell signaling were identified. This search
      was supplemented by a manual search of the Proceedings of the Annual Meetings of
      the American Association for Cancer Research, American Society of Clinical
      Oncology, and the American Association for Cancer Research (AARC)--European
      Organisation for Research and Treatment of Cancer (EORTC)--National Cancer
      Institute (NCI) Symposium on New Anticancer Drugs.

PMID- 15983387
TI  - Frag1, a homolog of alternative replication factor C subunits, links replication
      stress surveillance with apoptosis.
AB  - We report the identification and characterization of a potent regulator of
      genomic integrity, mouse and human FRAG1 gene, a conserved homolog of replication
      factor C large subunit that is homologous to the alternative replication factor C
      subunits Elg1, Ctf18/Chl12, and Rad24 of budding yeast. FRAG1 was identified in a
      search for key caretaker genes involved in the regulation of genomic stability
      under conditions of replicative stress. In response to stress, Atr participates
      in the down-regulation of FRAG1 expression, leading to the induction of apoptosis
      through the release of Rad9 from damaged chromatin during the S phase of the cell
      cycle, allowing Rad9-Bcl2 association and induction of proapoptotic Bax protein.
      We propose that the Frag1 signal pathway, by linking replication stress
      surveillance with apoptosis induction, plays a central role in determining
      whether DNA damage is compatible with cell survival or whether it requires cell
      elimination by apoptosis.

PMID- 15983389
TI  - Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell
      lymphoma.
AB  - PURPOSE: Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in
      overexpression of cyclin D1 messenger RNA. This study tested whether temsirolimus
      (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin
      kinase that regulates cyclin D1 translation, could produce tumor responses in
      patients with MCL. PATIENTS AND METHODS: Patients with relapsed or refractory MCL
      were eligible to receive temsirolimus 250 mg intravenously every week as a single
      agent. Patients with a tumor response after six cycles were eligible to continue
      drug for a total of 12 cycles or two cycles after complete remission, and were
      then observed without maintenance. RESULTS: Thirty-five patients were enrolled
      and were assessable for toxicity; one patient had MCL by histology but was cyclin
      D1 negative and was ineligible for efficacy. The median age was 70 years (range,
      38 to 89 years), 91% were stage 4, and 69% had two or more extranodal sites.
      Patients had received a median of three prior therapies (range, one to 11), and
      54% were refractory to the last treatment. The overall response rate was 38% (13
      of 34 patients; 90% CI, 24% to 54%) with one complete response (3%) and 12
      partial responses (35%). The median time-to-progression in all patients was 6.5
      months (95% CI, 2.9 to 8.3 months), and the duration of response for the 13
      responders was 6.9 months (95% CI, 5.2 to 12.4 months). Hematologic toxicities
      were the most common, with 71% (25 of 35 patients) having grade 3 and 11% (four
      of 35 patients) having grade 4 toxicities observed. Thrombocytopenia was the most
      frequent cause of dose reductions but was of short duration, typically resolving
      within 1 week. CONCLUSIONS: Single-agent temsirolimus has substantial antitumor
      activity in relapsed MCL. This study demonstrates that agents that selectively
      target cellular pathways dysregulated in MCL cells can produce therapeutic
      benefit. Further studies of this agent in MCL and other lymphoid malignancies are
      warranted.

PMID- 15983390
TI  - Effects of exemestane administered for 2 years versus placebo on bone mineral
      density, bone biomarkers, and plasma lipids in patients with surgically resected
      early breast cancer.
AB  - PURPOSE: To evaluate potential detrimental effects of exemestane on bone and
      lipid metabolism. PATIENTS AND METHODS: Postmenopausal women with early breast
      cancer were randomly assigned to exemestane 25 mg daily or placebo for 2 years in
      a double-blind setting. Primary objective was to evaluate the effect of
      exemestane on bone mineral density. Secondary objectives were effects on bone
      biomarkers, plasma lipids, coagulation factors, and homocysteine. Planned size
      was 128 patients. RESULTS: One hundred forty-seven patients were enrolled. All
      patients completed their 24-month visit except for those discontinuing treatment
      at an earlier stage. The mean annual rate of bone mineral density loss was 2.17%
      v 1.84% in the lumbar spine (P = .568) and 2.72% v 1.48% in the femoral neck (P =
      .024) in the exemestane and placebo arm, respectively. The mean change in T-score
      after 2 years was -0.21 for exemestane and -0.11 on placebo in the hip, and -0.30
      and -0.21, respectively, in the lumbar spine. Exemestane significantly increased
      serum level and urinary excretion of bone resorption, but also bone formation
      markers. Except for a modest reduction in high-density lipoprotein cholesterol (P
      < .001) and apolipoprotein A1 (P = .004), exemestane had no major effect on lipid
      profile, homocysteine levels, or coagulation parameters. CONCLUSION: Exemestane
      modestly enhanced bone loss from the femoral neck without significant influence
      on lumbar bone loss. Except for a 6% to 9% drop in plasma high-density
      lipoprotein cholesterol, no major effects on serum lipids, coagulation factors,
      or homocysteine were recorded. Bone mineral density should be assessed according
      to the US Preventive Services Task Force guidelines.

PMID- 15983391
TI  - Predictive value of bone resorption and formation markers in cancer patients with
      bone metastases receiving the bisphosphonate zoledronic acid.
AB  - PURPOSE: Three large, randomized trials of patients with bone metastases recently
      demonstrated that zoledronic acid reduces the risk of skeletal-related events.
      These trials provide an opportunity for investigating the correlation between
      bone metabolism and clinical outcome during bisphosphonate therapy. PATIENTS AND
      METHODS: Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline
      phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462
      with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell
      lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This
      exploratory cohort analysis grouped patients by baseline and most recent levels
      of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol
      creatinine), or high (> or = 100 nmol/mmol creatinine), and BAP as low (< 146
      U/L) or high (> or = 146 U/L). The relative risks for negative clinical outcomes
      were estimated for each group using multiple-event and Cox regression models with
      time-varying covariates. RESULTS: Patients with high and moderate Ntx levels had
      2-fold increases in their risk of skeletal complications and disease progression
      compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in
      each solid tumor category were associated with a 4- to 6-fold increased risk of
      death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared
      with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed
      some correlation with risk of negative clinical outcomes. CONCLUSION: The bone
      resorption marker Ntx provides valuable prognostic information in patients with
      bone metastases receiving bisphosphonates.

PMID- 15983392
TI  - Improved survival of follicular lymphoma patients in the United States.
AB  - PURPOSE: Despite several new treatment options, single- and multi-institution
      analyses have not clarified whether survival patterns in follicular lymphoma (FL)
      patients have changed in recent decades. We undertook a study using a large
      population-based registry to analyze survival patterns among patients with FL.
      PATIENTS AND METHODS: Surveillance, Epidemiology, and End Results morphology
      codes were used to identify 14,564 patients diagnosed with FL between 1978 and
      1999. Observed median survival times, Kaplan-Meier survival curves, proportional
      death hazard ratios, and relative survival rates were calculated. Joinpoint
      regression analysis was used to identify trends in annual adjusted death hazard
      ratios. RESULTS: An improvement in survival of all patients with FL was observed
      between each of three diagnosis eras (1978 to 1985, 1986 to 1992, and 1993 to
      1999) by log-rank tests. Among patients with stage-specific data, the median
      survival time improved from 84 months (95% CI, 81 to 88 months) in the 1983 to
      1989 era to 93 months (95% CI, 89 to 97 months) in the 1993 to 1999 era. Similar
      findings were identified across sex and age groups and for subsets including
      advanced-stage, large-cell FL and the combined subset of small cleaved- and mixed
      cell FL. The inter-era survival advantage observed in white patients was not
      observed for black patients. The relative risk of death decreased by 1.8% per
      year over the 1983 to 1999 observation period. CONCLUSION: The survival of
      patients with FL in the United States has improved over the last 25 years. The
      survival improvement may be a result of the sequential application of effective
      therapies and improved supportive care.

PMID- 15983393
TI  - Improved survival for patients with follicular lymphoma.

PMID- 15983394
TI  - Molecular targeting with cancer vaccines.

PMID- 15983395
TI  - Aromatase inhibitors and bone loss: risks in perspective.

PMID- 15983396
TI  - Immunization with mutant p53- and K-ras-derived peptides in cancer patients:
      immune response and clinical outcome.
AB  - PURPOSE: To determine the ability to induce tumor-specific immunity with
      individual mutant K-ras-or p53-derived peptides and to monitor clinical outcome.
      PATIENTS AND METHODS: Patients in varying stages of disease underwent genetic
      analysis for mutations in K-ras and p53. Thirty-nine patients were enrolled.
      Seventeen-mer peptides were custom synthesized to the corresponding mutation.
      Baseline immunity was assessed for cytotoxic T-lymphocyte (CTL) response and
      interferon gamma (IFN-gamma) release from mutant peptide-primed lymphocytes.
      Patients' peripheral-blood mononuclear cells were pulsed with the corresponding
      peptide, irradiated, and applied intravenously. Patients were observed for CTL,
      IFN-gamma, interleukin (IL) -2, IL-5, and granulocyte-macrophage colony
      stimulating factor responses, for treatment-related toxicity, and for tumor
      response. RESULTS: No toxicity was observed. Ten (26%) of 38 patients had
      detectable CTL against mutant p53 or K-ras, and two patients were positive for
      CTL at baseline. Positive IFN-gamma responses occurred in 16 patients (42%) after
      vaccination, whereas four patients had positive IFN-gamma reaction before
      vaccination. Of 29 patients with evident disease, five experienced a period of
      stable disease. Favorable prognostic markers were detectable CTL activity and a
      positive IFN-gamma reaction but not IL-5 release. Median survival times of 393 v
      98 days for a positive versus negative CTL response (P = .04), respectively, and
      of 470 v 88 days for a positive versus negative IFN-gamma response (P = .02),
      respectively, were detected. CONCLUSION: Custom-made peptide vaccination is
      feasible without any toxicity. CTL and cytokine responses specific to a given
      mutation can be induced or enhanced with peptide vaccines. Cellular immunity to
      mutant p53 and K-ras oncopeptides is associated with longer survival.

PMID- 15983397
TI  - Enrichment designs: efficiency in development of cancer treatments.

PMID- 15983398
TI  - High bone turnover markers predict poor outcome in patients with bone metastasis.

PMID- 15983399
TI  - Evaluation of randomized discontinuation design.
AB  - PURPOSE: Single-arm phase II trials may not be appropriate for testing cytostatic
      agents. We evaluate two kinds of randomized designs for the early development of
      target-based cytostatic agents. METHODS: We compared power of the randomized
      discontinuation and upfront randomization designs under two models for the
      treatment effect of targeted cytostatic agents. RESULTS: The randomized
      discontinuation design is not as efficient as upfront randomization if treatment
      has a fixed effect on tumor growth rate or if treatment benefit is restricted to
      slower-growing tumors. On the other hand, the randomized discontinuation design
      can be advantageous under a model where only a subset of patients, those
      expressing the molecular target, is sensitive to the agent. To achieve
      efficiency, the design parameters must be carefully structured to provide
      adequate enrichment of the randomly assigned patients. CONCLUSION: With careful
      planning, the randomized discontinuation designs can be useful in some settings
      in the early development of targeted agents where a reliable assay to select
      patients expressing the target is not available.

PMID- 15983400
TI  - The Snail genes as inducers of cell movement and survival: implications in
      development and cancer.
AB  - The functions of the Snail family of zinc-finger transcription factors are
      essential during embryonic development. One of their best-known functions is to
      induce epithelial to mesenchymal transitions (EMTs), which convert epithelial
      cells into migratory mesenchymal cells. In recent years, many orthologues of the
      Snail family have been identified throughout the animal kingdom, and their study
      is providing new clues about the EMT-dependent and -independent functions of
      Snail proteins. Here, we discuss these functions and how they influence cell
      behaviour during development and during diseases such as metastatic cancer. From
      these findings, we propose that Snail genes act primarily as survival factors and
      inducers of cell movement, rather than as inducers of EMT or cell fate.

PMID- 15983401
TI  - Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its
      export activity in Caenorhabditis elegans.
AB  - Multidrug resistance-associated proteins (MRPs), when overexpressed, confer drug
      resistance to cancer cells by exporting anti-cancer agents through the cell
      membrane, but their role in animal development has not been elucidated. Here we
      show that an MRP homolog regulates larval development in the nematode
      Caenorhabditis elegans. C. elegans forms a special third-stage larva called a
      dauer larva under conditions inappropriate for growth. By contrast, we found that
      mutants in mrp-1, an MRP homolog gene, form dauer larvae even under conditions
      appropriate for growth, in the background of certain mutations that partially
      block the insulin signaling pathway. A functional mrp-1::GFP gene was shown to be
      expressed in many tissues, and the wild-type mrp-1 gene must be expressed in
      multiple tissues for a wild-type phenotype. Human MRP1 could substitute for C.
      elegans MRP-1 in dauer larva regulation, and an inhibitor of the human MRP1
      transport activity impaired this function, showing that export activity is
      required for normal dauer larva regulation. Epistasis studies revealed that MRP-1
      acts in neither the TGF-beta nor the cGMP signaling pathway. mrp-1 mutations
      enhanced the dauer-constitutive phenotype of mutants in the insulin signaling
      pathway more strongly than that in other pathways. Thus, MRP-1, through its
      export activity, supports the induction of the normal (non-dauer) life cycle by
      the insulin signaling pathway.

PMID- 15983402
TI  - Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation
      and cartilage induction during axolotl tail regeneration.
AB  - Tail regeneration in urodeles requires the coordinated growth and patterning of
      the regenerating tissues types, including the spinal cord, cartilage and muscle.
      The dorsoventral (DV) orientation of the spinal cord at the amputation plane
      determines the DV patterning of the regenerating spinal cord as well as the
      patterning of surrounding tissues such as cartilage. We investigated this
      phenomenon on a molecular level. Both the mature and regenerating axolotl spinal
      cord express molecular markers of DV progenitor cell domains found during
      embryonic neural tube development, including Pax6, Pax7 and Msx1. Furthermore,
      the expression of Sonic hedgehog (Shh) is localized to the ventral floor plate
      domain in both mature and regenerating spinal cord. Patched1 receptor expression
      indicated that hedgehog signaling occurs not only within the spinal cord but is
      also transmitted to the surrounding blastema. Cyclopamine treatment revealed that
      hedgehog signaling is not only required for DV patterning of the regenerating
      spinal cord but also had profound effects on the regeneration of surrounding,
      mesodermal tissues. Proliferation of tail blastema cells was severely impaired,
      resulting in an overall cessation of tail regeneration, and blastema cells no
      longer expressed the early cartilage marker Sox9. Spinal cord removal experiments
      revealed that hedgehog signaling, while required for blastema growth is not
      sufficient for tail regeneration in the absence of the spinal cord. By contrast
      to the cyclopamine effect on tail regeneration, cyclopamine-treated regenerating
      limbs achieve a normal length and contain cartilage. This study represents the
      first molecular localization of DV patterning information in mature tissue that
      controls regeneration. Interestingly, although tail regeneration does not occur
      through the formation of somites, the Shh-dependent pathways that control
      embryonic somite patterning and proliferation may be utilized within the
      blastema, albeit with a different topography to mediate growth and patterning of
      tail tissues during regeneration.

PMID- 15983403
TI  - Zebrafish penner/lethal giant larvae 2 functions in hemidesmosome formation,
      maintenance of cellular morphology and growth regulation in the developing basal
      epidermis.
AB  - Epithelial cells are equipped with junctional complexes that are involved in
      maintaining tissue architecture, providing mechanical integrity and suppressing
      tumour formation as well as invasiveness. A strict spatial segregation of these
      junctional complexes leads to the polarisation of epithelial cells. In vertebrate
      epithelia, basally localised hemidesmosomes mediate stable adhesion between
      epithelial cells and the underlying basement membrane. Although components of
      hemidesmosomes are relatively well known, the molecular machinery involved in
      governing the formation of these robust junctions, remains elusive. Here, we have
      identified the first component of this machinery using a forward genetic approach
      in zebrafish as we show that the function of penner (pen)/lethal giant larvae 2
      (lgl2) is necessary for hemidesmosome formation and maintenance of the tissue
      integrity in the developing basal epidermis. Moreover, in pen/lgl2 mutant, basal
      epidermal cells hyper-proliferate and migrate to ectopic positions. Of the two
      vertebrate orthologues of the Drosophila tumour suppressor gene lethal giant
      larvae, the function of lgl2 in vertebrate development and organogenesis remained
      unclear so far. Here, we have unravelled an essential function of lgl2 during
      development of the epidermis in vertebrates.

PMID- 15983405
TI  - M. Sundaralingam (1931-2004): distinguished nucleic acid researcher.

PMID- 15983404
TI  - Cooperative requirement of the Gli proteins in neurogenesis.
AB  - The Gli proteins are critical components of multiple processes in development,
      homeostasis and disease, including neurogenesis and tumorigenesis. However, it is
      unclear how the Gli code, the sum of their combinatorial positive and negative
      functions, dictates cell fate and behavior. Using an antisense approach to
      knockdown gene function in vivo, we find that each of the three Gli proteins is
      required for the induction of all primary neurons in the amphibian neural plate
      and regulates the bHLH/Notch neurogenic cascade. Analyses of endogenous Gli
      function in Gli-mediated neurogenesis and tumorigenesis, and in animal cap
      assays, reveal specific requirements that are context specific. Nuclear
      colocalization and binding studies suggest the formation of complexes, with the
      first two zinc fingers of the Gli five zinc-finger domain acting as a protein
      protein interaction site. The Gli proteins therefore appear to form a dynamic
      physical network that underlies cooperative function, greatly extending the
      combinatorial possibilities of the Gli code, which may be further fine-tuned in
      cell fate specification by co-factor function.

PMID- 15983406
TI  - A robust bulk-solvent correction and anisotropic scaling procedure.
AB  - A reliable method for the determination of bulk-solvent model parameters and an
      overall anisotropic scale factor is of increasing importance as structure
      determination becomes more automated. Current protocols require the manual
      inspection of refinement results in order to detect errors in the calculation of
      these parameters. Here, a robust method for determining bulk-solvent and
      anisotropic scaling parameters in macromolecular refinement is described. The
      implementation of a maximum-likelihood target function for determining the same
      parameters is also discussed. The formulas and corresponding derivatives of the
      likelihood function with respect to the solvent parameters and the components of
      anisotropic scale matrix are presented. These algorithms are implemented in the
      CCTBX bulk-solvent correction and scaling module.

PMID- 15983407
TI  - Structure of human PNP complexed with ligands.
AB  - Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage
      pathway, which allows cells to utilize preformed bases and nucleosides in order
      to synthesize nucleotides. PNP is specific for purine nucleosides in the beta
      configuration and exhibits a strong preference for purines containing a 6-keto
      group and ribosyl-containing nucleosides relative to the corresponding analogues.
      PNP was crystallized in complex with ligands and data collection was performed
      using synchrotron radiation. This work reports the structure of human PNP in
      complex with guanosine (at 2.80 A resolution), 3'-deoxyguanosine (at 2.86 A
      resolution) and 8-azaguanine (at 2.85 A resolution). These structures were
      compared with the PNP-guanine, PNP-inosine and PNP-immucillin-H complexes solved
      previously.

PMID- 15983408
TI  - Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5
      substituted acyclouridines.
AB  - Uridine phosphorylase (UP) catalyzes the reversible phosphorolysis of uridine to
      uracil and ribose 1-phosphate and is a key enzyme in the pyrimidine-salvage
      pathway. Escherichia coli UP is structurally homologous to E. coli purine
      nucleoside phosphorylase and other members of the type I family of nucleoside
      phosphorylases. The structures of 5-benzylacyclouridine, 5
      phenylthioacyclouridine, 5-phenylselenenylacyclouridine, 5-m-benzyloxybenzyl
      acyclouridine and 5-m-benzyloxybenzyl barbituric acid acyclonucleoside bound to
      the active site of E. coli UP have been determined, with resolutions ranging from
      1.95 to 2.3 A. For all five complexes the acyclo sugar moiety binds to the active
      site in a conformation that mimics the ribose ring of the natural substrates.
      Surprisingly, the terminal hydroxyl group occupies the position of the
      nonessential 5'-hydroxyl substituent of the substrate rather than the 3'-hydroxyl
      group, which is normally required for catalytic activity. Until recently,
      inhibitors of UP were designed with limited structural knowledge of the active
      site residues. These structures explain the basis of inhibition for this series
      of acyclouridine analogs and suggest possible additional avenues for future drug
      design efforts. Furthermore, the studies can be extended to design inhibitors of
      human UP, for which no X-ray structure is available.

PMID- 15983409
TI  - Evaluation of protein crystallization states based on texture information derived
      from greyscale images.
AB  - In recent years, several projects have advanced research and development related
      to the automation of the protein crystallization process. However, evaluation of
      crystallization states has not yet been completely automated. In the usual
      crystallization process, researchers evaluate the protein crystallization growth
      states based on visual impressions and assign them a score over and over again.
      The method presented here automates this evaluation process. This method attempts
      to categorize the individual crystallization droplet images into five classes.
      The algorithm is comprised of pre-processing, feature extraction from images
      using texture analysis and a categorization process using linear discriminant
      analysis. The performance of this method has been evaluated by comparing the
      results obtained by using this method with the results from a human expert and
      the concordance rate was 90.6%.

PMID- 15983410
TI  - High-pressure cooling of protein crystals without cryoprotectants.
AB  - Flash-cooling of protein crystals is the best known method to effectively
      mitigate radiation damage in macromolecular crystallography. To prevent physical
      damage to crystals upon cooling, suitable cryoprotectants must usually be found,
      a process that is time-consuming and in some cases unsuccessful. A method is
      described to cool protein crystals in high-pressure helium gas without the need
      for penetrative cryoprotectants. The method involves mounting protein crystals
      from the native mother liquor in a cryoloop with a droplet of oil, pressurizing
      the crystal to 200 MPa in He gas, cooling the crystal under pressure and then
      releasing the pressure. The crystal is then removed from the apparatus under
      liquid nitrogen and handled thereafter like a normal cryocooled crystal. Results
      are presented from three representative proteins. Dramatic improvement in
      diffraction quality in terms of resolution and mosaicity was observed in all
      cases. A mechanism for the pressure cooling is proposed involving high-density
      amorphous (HDA) ice which is produced at high pressure and is metastable at room
      pressure and 110 K.

PMID- 15983411
TI  - The temperature of flash-cooling has dramatic effects on the diffraction quality
      of nucleosome crystals.
AB  - Nucleosome core-particle crystals are routinely flash-cooled in liquid propane at
      temperatures of approximately 153 K, followed by transfer into a cold nitrogen
      gas stream (approximately 93 K). Analysis of diffraction data from crystals flash
      cooled at different temperatures shows that the optimal temperature is
      approximately 153 K. The data quality worsens, with a concomitant reduction in
      the diffraction limit, at temperatures both higher and lower than 153 K. With
      some batches of crystals, significant shrinkage of the unit-cell volume is also
      observed at temperatures of 138 K and lower. The lattice shrinkage is always
      restricted to the c axis, concurrent with closer packing of two nucleosomes.
      Direct plunge-cooling of crystals in liquid nitrogen leads to loss of diffraction
      quality and resolution limit. Thus, in cases where flash-cooling into liquid
      nitrogen is detrimental to diffraction, optimizing cooling protocols at higher
      temperatures using liquid propane or other cryogens with similar properties may
      lead to dramatically improved results. In a related study, it is shown that a
      nucleosome crystal transported under 'cryocooled' conditions has higher mosaicity
      and yields inferior data quality in comparison to a crystal cryocooled at the
      synchrotron. For fragile crystals, transport in mother liquor and/or
      cryoprotectant followed by subsequent flash-cooling at the synchrotron may be the
      best procedure.

PMID- 15983412
TI  - Improving experimental phasing: the role of strongest reflections.
AB  - Very strong reflections have a dominant impact on the initial phasing and model
      building stages of structure determination. However, experimental phasing (MIR,
      SAD or MAD) fails on some of the strongest reflections when the heavy-atom
      contribution to scattering is relatively weak or absent. It is shown that when
      just a few (approximately 50-100) of these reflections are assigned low-error
      phases, the entire set of isomorphous replacement phases becomes significantly
      improved after density modification. This improvement is indicated by higher map
      correlation coefficients and reduced mean phase errors of the updated data. The
      problem of phasing the strongest reflections may be solved by the direct
      measurement of triplet phases in a three-beam diffraction experiment. The
      analysis shows that merging isomorphous replacement data with a limited number of
      highly accurate phases from the reference-beam diffraction experiment would
      significantly improve conventional experimental phasing.

PMID- 15983413
TI  - Structure of PEP carboxykinase from the succinate-producing Actinobacillus
      succinogenes: a new conserved active-site motif.
AB  - Actinobacillus succinogenes can produce, via fermentation, high concentrations of
      succinate, an important industrial commodity. A key enzyme in this pathway is
      phosphoenolpyruvate carboxykinase (PCK), which catalyzes the production of
      oxaloacetate from phosphoenolpyruvate and carbon dioxide, with the concomitant
      conversion of adenosine 5'-diphosphate to adenosine 5'-triphosphate. 1.85 and
      1.70 A resolution structures of the native and a pyruvate/Mn(2+)/phosphate
      complex have been solved, respectively. The structure of the complex contains
      sulfhydryl reducing agents covalently bound to three cysteine residues via
      disulfide bonds. One of these cysteine residues (Cys285) is located in the active
      site cleft and may be analogous to the putative reactive cysteine of PCK from
      Trypanosoma cruzi. Cys285 is also part of a previously unreported conserved motif
      comprising residues 280-287 and containing the pattern NXEXGXY(/F)A(/G); this new
      motif appears to have a structural role in stabilizing and positioning side
      chains that bind substrates and metal ions. The first few residues of this motif
      connect the two domains of the enzyme and a fulcrum point appears to be located
      near Asn280. In addition, an active-site Asp residue forms two coordinate bonds
      with the Mn(2+) ion present in the structure of the complex in a symmetrical
      bidentate manner, unlike in other PCK structures that contain a manganese ion.

PMID- 15983414
TI  - Structure of a closed-form uroporphyrinogen-III C-methyltransferase from Thermus
      thermophilus.
AB  - Uroporphyrinogen-III C-methyltransferase from Thermus thermophilus is a
      multifunctional protein responsible for two of the eight S-adenosyl-methionine
      dependent methylations of the corrin ring during vitamin B(12) synthesis. The
      structure of this protein has been solved to 2.0 A resolution in both the apo and
      cofactor-bound form. The monomer consists of two domains, A and B, each
      consisting of a five-stranded beta-sheet and two or three alpha-helices, with the
      cofactor bound at the interface. The biological unit is the dimer found in the
      asymmetric unit. This dimer is related by a non-crystallographic twofold such
      that two B domains combine to form a long ten-stranded beta-sheet. When compared
      with solved related structures, this structure shows clear differences in the
      region involved in cofactor and substrate binding, affirming the role of several
      previously implicated residues and questioning others. The solved related
      structures are characterized by an exposed active site. The T. thermophilus
      structure has this site restricted by the interaction of a flexible loop
      structure with a highly conserved residue, suggesting a mechanistic role. This
      structure represents the ;closed' form of the protein.

PMID- 15983415
TI  - Following directed evolution with crystallography: structural changes observed in
      changing the substrate specificity of dienelactone hydrolase.
AB  - The enzyme dienelactone hydrolase (DLH) has undergone directed evolution to
      produce a series of mutant proteins that have enhanced activity towards the non
      physiological substrates alpha-naphthyl acetate and p-nitrophenyl acetate. In
      terms of steady-state kinetics, the mutations caused a drop in the K(m) for the
      hydrolysis reaction with these two substrates. For the best mutant, there was a
      5.6-fold increase in k(cat)/K(m) for the hydrolysis of alpha-naphthyl acetate and
      a 3.6-fold increase was observed for p-nitrophenyl acetate. For alpha-naphthyl
      acetate the pre-steady-state kinetics revealed that the rate constant for the
      formation of the covalent intermediate had increased. The mutations responsible
      for the rate enhancements map to the active site. The structures of the starting
      and mutated proteins revealed small changes in the protein owing to the
      mutations, while the structures of the same proteins with an inhibitor co
      crystallized in the active site indicated that the mutations caused significant
      changes in the way the mutated proteins recognized the substrates. Within the
      active site of the mutant proteins, the inhibitor was rotated by about 180
      degrees with respect to the orientation found in the starting enzyme. This
      rotation of the inhibitor caused the displacement of a large section of a loop on
      one side of the active site. Residues that could stabilize the transition state
      for the reaction were identified.

PMID- 15983416
TI  - Correction of X-ray intensities from an HslV-HslU co-crystal containing lattice
      translocation defects.
AB  - Because of lattice-translocation defects, two identical but translated lattices
      can coexist as a single coherent mosaic block in a crystal. The observed
      structure in such cases is a weighted sum of two identical but translated
      structures, one from each lattice; the observed structure factors are a weighted
      vector sum of the structure factors with identical unit amplitudes but shifted
      phases. The correction of X-ray intensities from a single crystal containing
      these defects of the hybrid HslV-HslU complex, which consists of Escherichia coli
      HslU and Bacillus subtilis HslV (also known as CodW), is reported. When
      intensities are not corrected, a biologically irrelevant complex (with CodW from
      one lattice and HslU from another) is implied to exist. Only upon correction does
      a biologically functional CodW-HslU complex structure emerge.

PMID- 15983417
TI  - Structure of insect-cell-derived IL-22.
AB  - The crystal structure of interleukin-22 expressed in Drosophila melanogaster S2
      cells (IL-22(Dm)) has been determined at 2.6 A resolution. IL-22(Dm) crystals
      contain six molecules in the asymmetric unit. Comparison of IL-22(Dm) and IL
      22(Ec) (interleukin-22 produced in Escherichia coli) structures reveals that N
      linked glycosylation causes only minor structural changes to the cytokine.
      However, 1-4 A main-chain differences are observed between the six IL-22(Dm)
      monomers at regions corresponding to the IL-22R1 and IL-10R2 binding sites. The
      structure of the carbohydrate and the conformational variation of IL22(Dm)
      provide new insights into IL-22 receptor recognition.

PMID- 15983418
TI  - SGXPro: a parallel workflow engine enabling optimization of program performance
      and automation of structure determination.
AB  - SGXPro consists of four components. (i) A parallel workflow engine that was
      designed to automatically manage communication between the different processes
      and build systematic searches of algorithm/program/parameter space to generate
      the best possible result for a given data set. This is performed by offering the
      user a palette of programs and techniques commonly used in X-ray structure
      determination in an environment that lets the user choose programs in a mix-and
      match manner, without worrying about inter-program communication and file
      formats, during the structure-determination process. The current SGXPro program
      palette includes 3DSCALE, SHELXD, ISAS, SOLVE/RESOLVE, DM, SOLOMON, DMMULTI,
      BLAST, AMoRe, EPMR, XTALVIEW, ARP/wARP and MAID. (ii) A client/server
      architecture that allows the user to utilize the best computing facility
      available. (iii) Plug-in-and-play design, which allows easily integration of new
      programs into the system. (iv) User-friendly interface.

PMID- 15983419
TI  - Away from the edge II: in-house Se-SAS phasing with chromium radiation.
AB  - Recently, the demands of high-throughput macromolecular crystallography have
      driven continuous improvements in phasing methods, data-collection protocols and
      many other technologies. Single-wavelength anomalous scattering (SAS) phasing
      with chromium X-ray radiation opens a new possibility for phasing a protein with
      data collected in-house and has led to several successful examples of de novo
      structure solution using only weak anomalous scatterers such as sulfur. To
      further reduce data-collection time and make SAS phasing more robust, it is
      natural to combine selenomethionine-derivatized protein (SeMet protein) with Cr
      Kalpha radiation to take advantage of the larger anomalous scattering signal from
      selenium (f'' = 2.28 e(-)) compared with sulfur (f'' = 1.14 e(-)). As reported
      herein, the crystal structure of a putative chorismate mutase from Clostridium
      thermocellum was determined using Se-SAS with Cr Kalpha radiation. Each protein
      molecule contains eight selenomethionine residues in 148 amino-acid residues,
      providing a calculated Bijvoet ratio of about 3.5% at the Cr Kalpha wavelength. A
      single data set to 2.2 A resolution with approximately ninefold redundancy was
      collected using an imaging-plate detector coupled with a Cr source. Structure
      solution, refinement and deposition to the Protein Data Bank were performed
      within 9 h of the availability of the scaled diffraction data. The procedure used
      here is applicable to many other proteins and promises to become a routine
      pathway for in-house high-throughput crystallography.

PMID- 15983420
TI  - Pathological crystallography: case studies of several unusual macromolecular
      crystals.
AB  - Although macromolecular crystallography is rapidly becoming largely routine owing
      to advances in methods of data collection, structure solution and refinement,
      difficult cases are still common. To remind structural biologists about the kinds
      of crystallographic difficulties that might be encountered, case studies of
      several successfully completed structure determinations that utilized less than
      perfect crystals are discussed here. The structure of the proteolytic domain of
      Archaeoglobus fulgidus Lon was solved with crystals that contained superimposed
      orthorhombic and monoclinic lattices, a case not previously described for
      proteins. Another hexagonal crystal form of this protein exhibited an unusually
      high degree of non-isomorphism. Crystals of A. fulgidus Rio1 kinase exhibited
      both pseudosymmetry and twinning. Ways of identifying the observed phenomena and
      approaches to solving and refining macromolecular structures when only less than
      perfect crystals are available are discussed here.

PMID- 15983421
TI  - Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
AB  - A novel statistical approach to the phase problem in X-ray crystallography was
      introduced in a recent paper [Xu & Hauptman (2004), Acta Cryst. A60, 153-157]. In
      this approach, a new minimal function based on the statistical distribution of
      structure-invariant values serves as the foundation of an optimization procedure
      called statistical Shake-and-Bake. Favorable application of this procedure to Se
      atom substructure determination depends on the choice of the statistical interval
      over which the function is defined. The effects of interval variation have been
      studied for 19 Se-atom substructures ranging in size from five to 70 Se atoms in
      the asymmetric unit and the results have shown an overall improvement in success
      rate relative to traditional Shake-and-Bake. Statistical Shake-and-Bake is being
      incorporated as the default optimization procedure in newly distributed versions
      of the SnB and BnP computer programs.

PMID- 15983422
TI  - The effects of flash-annealing on glycerol kinase crystals.
AB  - Reflection profiles from glycerol kinase crystals were analyzed to determine the
      effect of flash-cooling on mosaicity (eta) and peak intensity in order to reveal
      changes in mosaic domain structure and composition. The results showed that
      repeated flash-annealing causes a significant decrease in the averaged mosaicity
      along with an increase in the overall peak counts of reflections and an enhanced
      signal-to-noise ratio. Individual reflection-profile analysis revealed a mostly
      dual domain structure, showing the minimization of one domain as a result of
      flash-annealing.

PMID- 15983423
TI  - Ultrahigh-resolution study on Pyrococcus abyssi rubredoxin. I. 0.69 A X-ray
      structure of mutant W4L/R5S.
AB  - The crystal structure of Pyrococcus abyssi rubredoxin mutant W4L/R5S was solved
      by direct methods. The model of the air-oxidized protein was refined by partially
      restrained full-matrix least-squares refinement against intensity data to 0.69 A
      resolution. This first ultrahigh-resolution structure of a rubredoxin provides
      very detailed and precise information about the Fe(SCys)(4) centre and its
      environment, the peptide-backbone stereochemistry, H atoms and hydrogen bonds,
      static and dynamic disorder, the solvent structure and the electron-density
      distribution. P. abyssi rubredoxin W4L/R5S is the first of a series of mutants
      studied by atomic and ultrahigh-resolution X-ray crystallography which are
      expected to contribute to the understanding of structure-function relationships
      in iron-sulfur proteins.

PMID- 15983424
TI  - Effect of alcohols on protein hydration: crystallographic analysis of hen egg
      white lysozyme in the presence of alcohols.
AB  - Organic solvents are known to bring about dehydration of proteins, the molecular
      basis of which has remained uncharacterized. The dehydration effect in many cases
      leads to eventual unfolding of proteins through the macroscopic solvent effect.
      In some cases, the organic solvent molecules also bind to protein surfaces,
      thereby forcing local unfolding. The X-ray structure of hen egg-white lysozyme co
      crystallized in the presence of alcohols with varying hydrophobicities has been
      studied. It was noticed that although the alcohols have very little effect on the
      conformation of the overall protein structure, they profoundly affect protein
      hydration and disorder of the bound waters. Systematic analysis of the water
      structure around the lysozyme molecule suggests that an increasing order of
      hydrophobicity of alcohols is directly proportional to the higher number of
      weakly bound waters in the protein. As anticipated, the water molecules in the
      native structure with high temperature factors (>/=40 A(2)) attain higher
      disorder in the presence of alcohols. It is believed that the disorder induced in
      the water molecules is a direct consequence of alcohol binding.

PMID- 15983425
TI  - The anticancer agent ellipticine unwinds DNA by intercalative binding in an
      orientation parallel to base pairs.
AB  - Ellipticine is a natural plant product that has been found to be a powerful
      anticancer drug. Although still unclear, its mechanism of action is considered to
      be mainly based on DNA intercalation and/or the inhibition of topoisomerase II.
      Many experimental data suggest an intercalation based on stacking interactions
      along the major base-pair axis, but alternative binding modes have been proposed,
      in particular for ellipticine derivatives. The 1.5 A resolution structure of
      ellipticine complexed to a 6 bp oligonucleotide unveils its mode of binding and
      enables a detailed analysis of the distorting effects of the drug on the DNA.

PMID- 15983426
TI  - Initial (latent) polycythemia vera with thrombocytosis mimicking essential
      thrombocythemia.
AB  - Patients have previously been described who showed clinical signs and symptoms
      suggesting essential thrombocythemia (ET), but later transformed to polycythemia
      vera (PV). From a series of 344 patients with a sustained borderline to moderate
      erythrocytosis, 44 failed to conform initially with the diagnostic criteria of
      the WHO for PV, because of their low hemoglobin level. Twenty-three patients of
      this group presented with a thrombocytosis exceeding 600 x 10(9)/l and therefore
      suggested ET, but later developed full-blown PV. For comparison we investigated
      also 164 patients with manifest PV, 90 patients with ET and 22 patients with
      reactive thrombocytosis (Th). The histopathology of initial PV was evaluated by
      stepwise discriminant analysis of 17 standardized features. Quantity and left
      shifting of erythro- and granulopoiesis, giant forms and naked nuclei of
      megakaryocytes, cellularity and reticulin fibers proved to exert a significant
      relevance concerning differentiation from true ET and Th. In conclusion, initial
      PV with thrombocytosis is characterized by a special pattern of BM
      histopathology. Therefore, so-called masked PV in patients with ET or
      simultaneous PVR-1 gene expression and endogeneous erythroid colony growth in ET
      patients are probably in keeping with initial PV mimicking ET.

PMID- 15983427
TI  - Retrospective multicenter study of allogeneic peripheral blood stem cell
      transplantation followed by reduced-intensity conditioning or conventional
      myeloablative regimen.
AB  - This retrospective study compared the results of reduced-intensity conditioning
      stem cell transplantation (RIST) and a conventional myeloablative regimen (CST)
      followed by allogeneic peripheral blood stem cell transplantation. In this
      respect, 63 RISTs and 41 CSTs were performed at 5 transplantation centers in
      Korea between April 1998 and December 2002. The RIST group had more adverse
      pretransplant characteristics. More aggressive diseases, like acute myeloid or
      lymphoblastic leukemia, were included in the CST group, while the RIST group
      included more indolent diseases, like chronic myeloid leukemia or myeloma (p <
      0.001). The incidence of acute graft-versus-host disease (GVHD) grades 2-4 was
      29.1 and 57.9% for the RIST and CST groups, respectively (p = 0.010), yet the
      incidence of chronic GVHD was similar in the two groups (57.4 vs. 71.9%). With a
      median follow-up of 13 months (0.5-61 months, 17 months in 52 survivors), the 3
      year overall (OS) and disease-free survival (DFS) was similar in the RIST and CST
      groups (p = 0.965 for OS, p = 0.545 for DFS). In a multivariate analysis, RIST (p
      = 0.010), good performance status (p = 0.006) and a higher CD34+ cell dose (p =
      0.008) were all identified as independent favorable prognostic factors for OS.
      Accordingly, in the current study, RIST produced equivalent or acceptable results
      compared with CST in terms of OS. Therefore, a prospective randomized trial of
      RIST and CST is warranted.

PMID- 15983428
TI  - Inefficacy of piracetam in the prevention of painful crises in children and
      adolescents with sickle cell disease.
AB  - Analgesia and hydration remain the only safe treatment for painful crises of
      sickle cell disease; hydroxyurea is effective, but the toxicity is still a
      problem. Piracetam is a nootropic drug that has reportedly been effective and non
      toxic in sickle cell patients, but most studies were not placebo-controlled and
      included a small number of patients. The present study evaluated the drug in a
      double-blind crossed placebo-controlled clinical trial in 73 children and
      adolescents suffering from moderate to severe painful crises for 13 months.
      Information regarding frequency and severity of pain was acquired through monthly
      clinical evaluation, visits and house calls, and 4,300 weekly questionnaires
      filled out by the patients in their domiciles. A monthly pain score was
      calculated for each patient. Pain was the most frequent adverse manifestation of
      the disease stressing its significant bio-psycho-social impact. Although nearly
      all patients and relatives reported a better clinical course throughout the whole
      study, the drug was ineffective in the prevention of painful crises. This placebo
      effect may be ascribed to an unplanned and unsystematic 'cognitive-behavioural'
      management of the children. The pain score in the second semester of the study -
      both in the experimental and in the control groups - was significantly smaller
      than that in the first semester. In conclusion, piracetam was found to be
      ineffective in the prevention of painful crises; a powerful placebo effect due to
      adequate patient care was demonstrated.

PMID- 15983429
TI  - Long-term outcome of ph-negative acute lymphoblastic leukaemia in adults: a
      single centre experience.
AB  - BACKGROUND AND OBJECTIVES: In adult acute lymphoblastic leukaemia (ALL), unlike
      in childhood ALL, the percentage of long-term remitters and survivors has not
      improved significantly over the last decades. In the present analysis, we
      describe a series of adult ALL patients consecutively treated with the same
      regimen in order to analyse prognostic factors and treatment outcome as well as
      to define new risk-oriented strategies. DESIGN AND METHODS: From 1990 to 1998,
      102 newly diagnosed ALL patients were referred to our division, 83 of them were
      eligible for the present study. Median age was 31 years (range 13-76); 77.1% had
      B-lineage ALL and 22.9% T-lineage ALL; 36.1% showed associated myeloid markers.
      All patients received an induction phase treatment, consisting of a 4-week cycle
      with vincristine, daunorubicin, L-asparaginase and desametasone; the
      consolidation phase included cyclophosphamide, cytarabine, 6-mercaptopurine and
      central nervous system (CNS) prophylaxis, followed by three of months maintenance
      (methotrexate + 6-mercaptopurine), re-induction (4-week cycle with vincristine,
      adriamicin, desametasone), and 2-year maintenance with methotrexate + 6
      mercaptopurine. RESULTS: Complete remission (CR) was achieved in 66 patients
      (79.5%); 20.5% of patients were resistant. The relapse rate was 60.2%. There were
      10 CNS relapses (accounting for 12% of all patients, 15% of all CRs and 20% of
      all relapses). One patient had an ovarian and 2 had a breast relapse. Eleven
      patients remained in first continuous CR after chemotherapy. Median overall
      survival (OS) and disease-free survival (DFS) were 1.8 and 1.0 years,
      respectively, with a median follow-up of 5.6 years (range 0.3-12.1). Initial
      white blood cell count </=30 x 10(9)/l, age <35 years, and time to complete
      remission </=40 days were the most significant prognostic factors for OS (p <
      0.05). These three characteristics defined a group of patients with a better
      prognosis (5-year OS: 58%). They represented, however, only 18% in this series of
      adult patients. INTERPRETATION AND CONCLUSIONS: In our cohort, we were able to
      define a small subgroup of adult ALL patients with a better outcome. However, the
      majority of patients is at a high risk of failure when treated with standard
      protocols. There is a need for new, more active regimens for these patients.

PMID- 15983430
TI  - Maternal, neonatal and collection factors influencing the haematopoietic content
      of cord blood units.
AB  - BACKGROUND AND OBJECTIVES: Umbilical cord blood (UCB) contains haematopoietic
      stem cells and can be used as an alternative to bone marrow transplantation in
      certain cases. Engraftment was dependent upon the haematopoietic progenitor cell
      content of the cord blood units. This study was designed to investigate the
      influence of obstetric, neonatal and collection factors on the volume and
      haematopoietic content of UCB donations. MATERIAL AND METHODS: A retrospective
      analysis of obstetric and neonatal factors was performed from 300 cord blood
      donations in Valencia Cord Blood Bank. Maternal, neonatal and collection factors
      influencing cord blood quality measured as volume, total nucleated cell count,
      CD34+ cells and colony-forming units (CFU) were analysed. RESULTS: Bigger babies
      produced cord blood units with larger volume, higher cells counts, CFU and CD34
      cell counts. In the multivariate analysis, we found that both placental weight
      and mode of collection were predictor variables for total nucleated cell count,
      CD34 cells and CFU. CONCLUSION: Our study concludes that cord blood units must be
      collected before placental delivery and that birth weight, as an estimation of
      the placental weight, could be added to standard cord blood donors criteria in
      order to improve the bank efficiency.

PMID- 15983431
TI  - High expression of bcl-x(L) in K562 cells and its role in the low sensitivity of
      K562 to realgar-induced apoptosis.
AB  - Arsenic compounds (As(2)O(3 )or()As(4)S(4)) have been used successfully for the
      treatment of acute promyelocytic leukemia (APL) for quite a long time. It has
      been noticed that the sensitivity to apoptosis induced by As(2)O(3 )varies among
      various leukemia cells. It was reported by several groups that As(2)O(3) could
      induce apoptosis in APL-derived NB4 cells at concentrations of 0.5-1 mumol/l,
      whereas in other leukemia cells like K562, As(2)O(3) has no effects at the same
      concentration. K562 cells undergo apoptosis only when the concentration of
      As(2)O(3 )is greater than 2 mumol/l. Another arsenic compound, realgar
      (As(4)S(4)), a traditional Chinese mineral medicine, has been used to treat APL
      effectively and demonstrated to have lower toxicity than As(2)O(3). It would be
      interesting to know whether NB4 and K562 cells will show different sensitivity to
      realgar as well and if there is a difference, what is the cellular mechanism of
      it. In our present study, K562 cells were much less sensitive than NB4 cells to
      apoptosis induced by realgar. We confirm that the expression of bcl-x(L) is
      significantly higher in K562 cells than that in NB4 cells and is not
      downregulated upon realgar treatment. K562 cells become sensitive to realgar at
      clinically acceptable concentrations when bcl-x(L) expression level is
      downregulated by transfecting bcl-x(L) antisense RNA vector into the cells. Our
      results suggest that the increased bcl-x(L) expression in K562 cells contributes
      to its insensitivity to realgar-induced apoptosis.

PMID- 15983432
TI  - Fatal splenic rupture caused by infiltration of adult T cell leukemia cells.
AB  - The spleen is an immunological organ commonly involved in both hematological and
      nonhematological diseases. Pathological rupture of the spleen has been described
      in a variety of diseases affecting the spleen. Infections have been cited in most
      cases involving splenic rupture, but are rare in hematological malignancies
      despite frequent involvement of the spleen. The present report describes a fatal
      case of splenic rupture caused by infiltration of adult T cell leukemia cells and
      reports the mechanism of splenic rupture. The importance of rapid diagnosis and
      surgery is emphasized.

PMID- 15983433
TI  - Primary peripheral B cell lymphoma, Burkitt-like, of the cranial vault.
AB  - We report an autopsy case of malignant lymphoma of the cranial vault. The patient
      was an 85-year-old woman who exhibited a painless subcutaneous scalp lump
      associated with no neurological abnormalities. CT scan and magnetic resonance
      imaging of the head showed an extra-intra cranial isodensity lesion of the
      cranial vault. Autopsy revealed that the tumor was composed of medium-sized cells
      which were immunoreactive with CD45, CD20, CD79a, and CD10, and a diagnosis of
      peripheral B cell lymphoma, Burkitt-like, was made. Non-Hodgkin lymphoma
      originating from the cranial vault is extremely rare; a search of the English
      literature revealed only 16 previously reported cases. Herein, we review this
      singular calvarial lymphoma.

PMID- 15983434
TI  - TNF-alpha promoter gene polymorphism in patients with myelodysplastic syndrome.

PMID- 15983435
TI  - Interleukin-6 and interleukin-8 are elevated in the cerebrospinal fluid of
      infants exposed to chorioamnionitis.
AB  - BACKGROUND: The clinical or histologic diagnosis of chorioamnionitis has been
      associated with an increased risk of neuropathology and adverse neurologic
      outcomes in premature and term infants. Inflammatory cytokines have been
      implicated in the pathogenesis of these processes. The objective of this study
      was to determine whether exposure to chorioamnionitis and fetal inflammatory
      syndrome is associated with elevated concentrations of inflammatory cytokines
      (TNF-alpha, IL-6, and IL-8) in the CSF of term and preterm infants. METHODS:
      Eighty-four mother/infant pairs were studied, 54 infants were premature. Twenty
      eight showed signs of maternal (n = 14), or fetal (n = 14) inflammation based on
      placental pathology; mothers of 24 infants showed signs of clinical
      chorioamnionitis not confirmed by placental pathology and 32 infants were
      considered as 'controls' since they had only transient difficulty adjusting to
      extra-uterine life warranting evaluation for sepsis. The cytokine concentrations
      in the CSF were measured within 24 h of birth. RESULTS: When compared to the
      control group (IL-8 = 341 +/- 170 pg/ml and IL-6 = 7.4 +/- 1.8 pg/ml)
      significantly higher concentrations of IL-8 were detected in the CSF of infants
      exposed to clinical chorioamnionitis (1,854 +/- 878 pg/ml; p = 0.001) and
      maternal/fetal inflammation (1,754 +/- 787 pg/ml; p = 0.001) and of IL-6 in
      infants with maternal/fetal inflammation (47.6 +/- 45.1 pg/ml; p = 0.01).
      CONCLUSIONS: These results indicate that infants exposed to clinical
      chorioamnionitis, or inflammation in utero, experience at least a transient
      elevation in inflammatory cytokines in CSF.

PMID- 15983436
TI  - Rate of admission and long-term prognosis among patients with acute chest pain in
      the 1990s compared with the 1980s.
AB  - We describe the incidence of acute chest pain (requiring admission to the
      emergency department) and the prognosis during two time periods in all patients
      admitted to the emergency department at Sahlgrenska University Hospital in
      Goteborg, Sweden, with acute chest pain 1986 and 1987 (period 1) and 1996 and
      1997 (period 2). The rate of admission for chest pain/100,000 inhabitants was
      4.7/day during period 1 and 5.0/day during period 2. The risk ratio for death
      adjusted for eight risk factors during period 2 in relation to period 1 was 0.88
      (95% CI 0.79-0.97). There was a significant interaction between time period and
      the severity of the final diagnosis (p=0.02), indicating a greater reduction in
      mortality among patients with acute myocardial infarction.

PMID- 15983437
TI  - What can we learn from animal models of Alopecia areata?
AB  - Alopecia areata (AA) is a hair loss disease marked by a focal inflammatory
      infiltrate of dystrophic anagen stage hair follicles by CD4+ and CD8+
      lymphocytes. Although AA is thought to be an autoimmune disorder, definitive
      proof is lacking. Moreover, characterization of the primary pathogenic mechanisms
      by which hair loss is induced in AA is limited. In this context, animal models
      may provide a vital contribution to understanding AA. Recent research using
      animal models of AA has focused on providing evidence in support of a lymphocyte
      mediated pathogenic mechanism consistent with AA as an autoimmune disease. In the
      future, research with both humans and animal models shall likely concentrate on
      identifying the primary antigenic epitopes involved in AA and the genetics of AA
      susceptibility. With a comprehensive understanding of the key elements in AA
      pathogenesis, new avenues for therapeutic research and intervention will be
      defined.

PMID- 15983438
TI  - Trichoscan: what is new?
AB  - The treatment of androgenetic alopecia (AGA) is usually long lasting, and the
      effects of treatment attempts are difficult to measure. Consequently, there was a
      need for a sensitive tool to monitor hair loss and treatment response. Therefore,
      we developed the Trichoscan as a method which combines epiluminescence microscopy
      with automatic digital image analysis for the measurement of human hair. The
      Trichoscan is able to analyze all important parameters of hair growth (density,
      diameter, growth rate, vellus and terminal hair density) with an intraclass
      correlation of approximately 91% within the same Trichoscan operator and an
      intraclass correlation of approximately 97% for different Trichoscan operators.
      The application of the technique was demonstrated by comparison of the hair
      parameters in 9 men with frontal balding which were treated for 6 months with 5%
      minoxidil. Even in this small cohort of patients, we noticed after 3 months of
      treatment compared to baseline a significant increase in hair density (+21.3
      hairs/cm2; p = 0.047) and cumulative hair thickness (+0.61 mm; p = 0.008) and
      after 6 months a significant increase in hair density (+34 hairs/cm2; p = 0.011)
      and cumulative hair thickness (+0.88 mm; p = 0.010). The study shows that the
      Trichoscan has many advantages. It can be used for clinical studies to compare
      placebo versus treatment or to compare the relative potencies of different hair
      growth-promoting substances. It can be used for studying AGA or other forms of
      diffuse hair loss, and it can be adopted to study the effect of drugs or laser
      treatment on hypertrichosis or hirsutism. The drawbacks, however, are that the
      Trichoscan still needs a hair dye for contrast enhancement and the measurement
      area must be clipped before analysis. This mini-review summarizes recent attempts
      to optimize the technique and shows new options such as the calculation of
      follicular units or the 'anagen hair count'.

PMID- 15983439
TI  - Hair shaft abnormalities--clues to diagnosis and treatment.
AB  - Hair dysplasias are congenital or acquired alterations which often involve the
      hair shaft. Hair shaft abnormalities are characterized by changes in color,
      density, length and structure. Hair shaft alterations often result from
      structural changes within the hair fibers and cuticles which may lead to brittle
      and uncombable hair. The hair of patients with hair shaft diseases feels dry and
      looks lusterless. Hair shaft diseases may occur as localized or generalized
      disorders. Genetic predisposition or exogenous factors produce and maintain hair
      shaft abnormalities. Hair shaft diseases are separated into those with and those
      without increased hair fragility. In general, optic microscopy and polarized
      light microscopy of hair shafts provide important clues to the diagnosis of
      isolated hair shaft abnormalities or complex syndromes. To establish an exact
      diagnosis of dysplastic hair shafts, a structured history and physical
      examination of the whole patient are needed which emphasizes other skin
      appendages such as the nails, sweat and sebaceous glands. Profound knowledge on
      hair biology and embryology is necessary to understand the different symptom
      complexes. Therapy of hair shaft disorders should focus on the cause. In
      addition, minimizing traumatic influences to hair shafts, such as drying hair
      with an electric dryer or permanent waves and dyes, is important. A short
      hairstyle is more suitable for patients with hair shaft disorders.

PMID- 15983440
TI  - Is baldness bad for the heart?
AB  - Various skin conditions are considered to be characteristic markers for elevated
      coronary disease risk. Over and above these established signs there are reports
      on other skin signs with possible associations with elevated coronary disease
      risk, i.e. the horizontal earlobe crease, high breast hair density, precocious
      graying and male pattern hair loss. A review of the literature is presented in
      this article, and the relevance of these symptoms is discussed as they are
      related to the possible myocardial disease risk. The available data on this topic
      are impressive, but on close assessment most of the studies are marred by
      methodical errors.

PMID- 15983441
TI  - Growth hormone treatment of short stature: status of the quality of life
      rationale.
AB  - The unlimited availability of biosynthetic human growth hormone (rhGH) has
      contributed to the disassociation of the treatment of short stature from its
      causes. The rationale for treatment has traditionally rested upon the assumption
      that short stature, in the extreme, may constitute a physical disability, and
      otherwise represents a significant psychosocial burden for the individual. This
      review summarizes what is known about the psychosocial aspects of short stature
      and the quality of life benefits of rhGH treatment. Stereotypes and assumptions
      about short stature are evaluated in light of empirical findings. Problems of
      psychosocial adjustment are relatively common in the general population. Because
      of the salience of short stature, and its potential to serve as a lightning rod
      to divert attention from other factors interfering with a healthy psychological
      adaptation, the clinician must be watchful of misattributions for ongoing
      problems, or unrealistic predictions of the benefits of taller stature. For these
      reasons, the clinician should consider incorporating a psychosocial component in
      the diagnostic evaluation to broaden potential treatment recommendations.
      Finally, studies of factors influencing family decisions regarding factors for
      and against rhGH therapy provide important clues to how clinicians might enhance
      the informed consent process.

PMID- 15983442
TI  - Evaluation of nasal mucociliary functions with rhinoscintigraphy in coal workers'
      pneumoconiosis.
AB  - OBJECTIVE: To compare nasal mucociliary clearance (NMC) functions in coal workers
      with pneumoconiosis, coal workers without pneumoconiosis and healthy controls by
      using technetium-99m-labeled macroaggregated albumin rhinoscintigraphy. METHODS:
      Sixty-five of the 86 coal workers were clinically documented as suffering from
      coal workers' pneumoconiosis (CWP group). CWP workers were divided into two
      groups according to smoking status: 44 smokers (CWP-S) and 21 nonsmokers (CWP
      NS). Twenty-one workers without pneumoconiosis (NCWP group) were similarly
      divided into two groups: 12 smokers (NCWP-S) and 9 nonsmokers (NCWP-NS). Thirty
      three healthy male volunteers were selected for the control group [15 smokers
      (control-S), 18 nonsmokers (control-NS)]. The half-time (t1/2) value for the
      clearance of the radiopharmaceutical was calculated for each patient. RESULTS:
      Mean t1/2 values for CWP-S, CWP-NS, NCWP-S, NCWP-NS, control-S and control-NS
      were 25.10 +/- 7.75, 10.97 +/- 3.24, 14.68 +/- 4.98, 9.17 +/- 3.71, 19.15 +/-
      5.04 and 15.08 +/- 5.11, respectively (p < 0.001, Kruskal-Wallis variance
      analysis). Further, mean t1/2 values of smokers versus nonsmokers in CWP, NCWP
      and control groups were compared, and it was found that although smoking
      prolonged nasal transport time in all three groups, the difference was
      significant only in the CWP group (p < 0.001, p < 0.023 and p < 0.027,
      respectively, Bonferroni-adjusted Mann-Whitney test). CONCLUSION: Our findings
      demonstrated a synergistic detrimental effect of smoking with coal dust exposure
      on nasal transport time.

PMID- 15983443
TI  - The characteristics of disseminated tumor cells in pancreatic cancer: a black box
      needs to be explored.
AB  - Despite recent advances in early diagnosis and surgical treatment, the clinical
      outcome of patients with pancreatic cancer has not been improved markedly. One of
      the reasons for the dismal outcome is early dissemination of tumor cells.
      Sensitive immunohistocytochemical and nucleic acid-based assays have detected
      disseminated tumor cells in the lymph nodes, bone marrow, peritoneal cavity or
      peripheral blood. Formation of the metastatic disease depends on the nature of
      the disseminated tumor cells. Standardization of protocols is mandatory to detect
      occult tumor cells in clinical practice. We present an overview of recent studies
      on the incidence, prognostic values and some characteristics of occult tumor
      cells disseminated in the secondary sites of patients with pancreatic cancer.

PMID- 15983444
TI  - Gene expression analysis of pancreatic cell lines reveals genes overexpressed in
      pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is one of the leading causes of cancer-related
      death. Using DNA gene expression analysis based on a custom made Affymetrix
      cancer array, we investigated the expression pattern of both primary and
      established pancreatic carcinoma cell lines. METHODS: We analyzed the gene
      expression of 5 established pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan
      1, Capan-2 and HPAF II) and 5 primary isolates, 1 of them derived from benign
      pancreatic duct cells. RESULTS: Out of 1,540 genes which were expressed in at
      least 3 experiments, we found 122 genes upregulated and 18 downregulated in tumor
      cell lines compared to benign cells with a fold change >3. Several of the
      upregulated genes (like Prefoldin 5, ADAM9 and E-cadherin) have been associated
      with pancreatic cancer before. The other differentially regulated genes, however,
      play a so far unknown role in the course of human pancreatic carcinoma. By means
      of immunohistochemistry we could show that thymosin beta-10 (TMSB10), upregulated
      in tumor cell lines, is expressed in human pancreatic carcinoma, but not in non
      neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis
      of pancreatic carcinoma. CONCLUSION: Using gene expression profiling of
      pancreatic cell lines we were able to identify genes differentially expressed in
      pancreatic adenocarcinoma, which might contribute to pancreatic cancer
      development.

PMID- 15983445
TI  - Pseudomyxoma peritonei accompanied by intraductal papillary mucinous neoplasm of
      the pancreas.
AB  - We describe a case of pseudomyxoma peritonei (PMP) successfully managed with
      intraperitoneal hyperthermic chemoperfusion. This case is unique due to the
      concurrent presence of intraductal papillary mucinous neoplasm (IPMN) of the
      pancreas. The patient presented with abdominal fullness. Abdominal computed
      tomography revealed massive ascites, thickened peritoneum, and a cystic lesion of
      the pancreas. Cytological examination of ascitic fluid sample showed mucin-rich
      atypical cells. Endoscopic retrograde pancreatography revealed a cystic lesion
      with the defect probably due to mural nodule and mucin, communicating with the
      pancreatic duct. At exploratory laparotomy, massive ascites and multiple nodules
      were identified within the peritoneal cavity. No primary tumour, including
      mucinous neoplasm of the appendix, was found. Histopathological examination of
      the omentum showed mucinous adenocarcinoma in pools of mucoid material,
      consistent with PMP. The relation between PMP and IPMN of the pancreas was
      possible, but not conclusive. The patient received intraperitoneal perfusion of
      saline heated to 42 degrees C containing cisplatin, etoposide, and mitomycin C,
      followed by 24 courses of postoperative chemotherapy with gemcitabine. The
      patient remains in good general condition with no signs of progression of PMP for
      2 years, but with a gradual and progressive enlargement of the pancreatic cystic
      lesion.

PMID- 15983446
TI  - From the laboratory to the bedside: searching for an understanding of
      anaphylaxis.

PMID- 15983447
TI  - Incisional sensitivity and pain measurements: dissecting mechanisms for
      postoperative pain.

PMID- 15983448
TI  - What's wrong with this label?

PMID- 15983450
TI  - Inspired oxygen fraction of 0.8 does not attenuate postoperative nausea and
      vomiting after strabismus surgery.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is a distressing problem
      after strabismus surgery. An inspired oxygen fraction has been reported to
      decrease PONV in patients after colon resection and to be more effective than
      ondansetron after gynecologic laparoscopy. Therefore, in a randomized,
      prospective, placebo-controlled study, the authors tested whether an inspired
      oxygen fraction of 0.8 decreases PONV in patients undergoing strabismus surgery
      and whether oxygen is more effective than ondansetron. METHODS: With approval of
      the authors' institutional review board, 210 patients were randomly assigned to
      receive one of three treatments: (1) 30% inspired oxygen in air plus intravenous
      administration of saline, (2) 80% inspired oxygen in air plus intravenous
      administration of saline, or (3) 30% inspired oxygen in air plus 75 microg/kg
      ondansetron intravenously during induction. General anesthesia was standardized
      and included etomidate, alfentanil, and mivacurium for induction and sevoflurane
      for maintenance. PONV was evaluated 6 and 24 h postoperatively by an investigator
      unaware of treatment assignment. RESULTS: Overall postoperative incidence of
      nausea and vomiting was 41% for inspired oxygen fraction of 0.3 plus placebo, 38%
      for inspired oxygen fraction of 0.8 plus placebo, and 28% for inspired oxygen
      fraction of 0.3 plus ondansetron, respectively (P = 0.279). Therefore, there was
      no statistically significant difference of PONV incidence among groups.
      CONCLUSIONS: An inspired oxygen fraction of 0.8 during general anesthesia with
      sevoflurane does not decrease PONV in patients undergoing strabismus repair.
      Ondansetron also did not significantly decrease PONV in our study setting.

PMID- 15983451
TI  - Attenuated brain response to auditory word stimulation with sevoflurane: a
      functional magnetic resonance imaging study in humans.
AB  - BACKGROUND: Functional magnetic resonance imaging offers a compelling, new
      perspective on altered brain function but is sparsely used in studies of
      anesthetic effect. To examine effects on verbal memory encoding, the authors
      imaged human brain response to auditory word stimulation using functional
      magnetic resonance imaging at different concentrations of an agent not previously
      studied, and tested memory after recovery. METHODS: Six male volunteers were
      studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and
      light states, respectively) via laryngeal mask. In each condition, they heard 15
      two-syllable English nouns via closed headphones. Each word was repeated 15 times
      (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain
      activations during blocks of stimulation versus rest were assessed with a 3-T
      Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested
      approximately 1.5 h after recovery with an auditory recognition task (chance
      performance = 33% correct). RESULTS: Scans showed widespread activations (P <
      0.005, uncorrected) in the awake state, including bilateral superior temporal,
      frontal, and parietal cortex, right occipital cortex, bilateral thalamus,
      striatum, hippocampus, and cerebellum; more limited activations in the light
      state (bilateral superior temporal gyrus, right thalamus, bilateral parietal
      cortex, left frontal cortex, and right occipital cortex); and no significant
      auditory-related activation in the deep state. During recognition testing,
      subjects correctly selected 77 +/- 12% of words presented while they were awake
      as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and
      deep stages, respectively. CONCLUSIONS: Sevoflurane induces dose-dependent
      suppression of auditory blood oxygenation level-dependent signals, which likely
      limits the ability of words to be processed during anesthesia and compromises
      memory.

PMID- 15983452
TI  - Sympathetic and hemodynamic effects of moderate and deep sedation with propofol
      in humans.
AB  - BACKGROUND: The objective of this study was to determine the mechanisms involved
      in the hypotension associated with sedative doses of propofol in humans. METHODS:
      Ten healthy volunteers (aged 21-37 yr) participated on two occasions and in
      random order received placebo or propofol infusions. Standard monitoring and
      radial artery blood pressure were combined with measurement of forearm blood flow
      (plethysmography) and derivation of forearm vascular resistance, recording of
      peroneal nerve sympathetic activity, and blood sampling for norepinephrine
      concentrations. A computer-controlled infusion pump delivered placebo or two
      concentrations of propofol, adjusted to achieve moderate and deep sedation based
      on the Observer Assessment of Alertness/Sedation score (responsiveness component)
      of 4 and 3. Level of sedation was quantitated using bispectral analysis of the
      electroencephalogram. Baroreflexes were assessed with a hypotensive challenge via
      administration of sodium nitroprusside. RESULTS: Baseline neurocirculatory and
      respiratory parameters did not differ between sessions. Progressive infusions to
      achieve moderate and deep sedation resulted in average Bispectral Index values of
      70 and 54, respectively. Propofol significantly reduced sympathetic nerve
      activity at both levels of sedation and decreased norepinephrine and forearm
      vascular resistance at deep sedation. These effects resulted in significant
      decreases in mean blood pressure of 9% and 18% at moderate and deep sedation,
      respectively. Propofol also reduced reflex increases in sympathetic nerve
      activity. CONCLUSIONS: These data from healthy subjects indicate that sedation
      doses of propofol, which did not compromise respiratory function, had substantial
      inhibitory effects on sympathetic nerve activity and reflex responses to
      hypotension resulting in vasodilation and significant decreases in mean blood
      pressure.

PMID- 15983453
TI  - Effect of intraoperative fluid management on outcome after intraabdominal
      surgery.
AB  - BACKGROUND: The debate over the correct perioperative fluid management is
      unresolved. METHODS: The impact of two intraoperative fluid regimes on
      postoperative outcome was prospectively evaluated in 152 patients with an
      American Society of Anesthesiologists physical status of I-III who were
      undergoing elective intraabdominal surgery. Patients were randomly assigned to
      receive intraoperatively either liberal (liberal protocol group [LPG], n = 75;
      bolus of 10 ml/kg followed by 12 ml x kg(-1) x h(-1)) or restrictive (restrictive
      protocol group [RPG], n = 77; 4 ml x kg(-1) x h(-1)) amounts of lactated Ringer's
      solution. The primary endpoint was the number of patients who died or experienced
      complications. The secondary endpoints included time to initial passage of flatus
      and feces, duration of hospital stay, and changes in body weight, hematocrit, and
      albumin serum concentration in the first 3 postoperative days. RESULTS: The
      number of patients with complications was lower in the RPG (P = 0.046). Patients
      in the LPG passed flatus and feces significantly later (flatus, median [range]: 4
      [3-7] days in the LPG vs. 3 [2-7] days in the RPG; P < 0.001; feces: 6 [4-9] days
      in the LPG vs. 4 [3-9] days in the RPG; P < 0.001), and their postoperative
      hospital stay was significantly longer (9 [7-24] days in the LPG vs. 8 [6-21]
      days in the RPG; P = 0.01). Significantly larger increases in body weight were
      observed in the LPG compared with the RPG (P < 0.01). In the first 3
      postoperative days, hematocrit and albumin concentrations were significantly
      higher in the RPG compared with the LPG. CONCLUSIONS: In patients undergoing
      elective intraabdominal surgery, intraoperative use of restrictive fluid
      management may be advantageous because it reduces postoperative morbidity and
      shortens hospital stay.

PMID- 15983454
TI  - Management of the difficult airway: a closed claims analysis.
AB  - BACKGROUND: The purpose of this study was to identify the patterns of liability
      associated with malpractice claims arising from management of the difficult
      airway. METHODS: Using the American Society of Anesthesiologists Closed Claims
      database, the authors examined 179 claims for difficult airway management between
      1985 and 1999 where a supplemental data collection tool was used and focused on
      airway management, outcomes, and the role of the 1993 Difficult Airway Guidelines
      in litigation. Chi-square tests and multiple logistic regression analysis
      compared risk factors for death or brain damage (death/BD) from two time periods:
      1985-1992 and 1993-1999. RESULTS: Difficult airway claims arose throughout the
      perioperative period: 67% upon induction, 15% during surgery, 12% at extubation,
      and 5% during recovery. Death/BD with induction of anesthesia decreased in 1993
      1999 (35%) compared with 1985-1992 (62%; P < 0.05; odds ratio, 0.26; 95%
      confidence interval, 0.11-0.63; P = 0.003). In contrast, death/BD associated with
      other phases of anesthesia did not significantly change over the time periods.
      The odds of death/BD were increased by the development of an airway emergency
      (odds ratio, 14.98; 95% confidence interval, 6.37-35.27; P < 0.001). During
      airway emergencies, persistent intubation attempts were associated with death/BD
      (P < 0.05). Since 1993, the Airway Guidelines were used to defend care (8%) and
      criticize care (3%). CONCLUSIONS: Death/BD in claims from difficult airway
      management associated with induction of anesthesia but not other phases of
      anesthesia decreased in 1993-1999 compared with 1985-1992. Development of
      additional management strategies for difficult airways encountered during
      maintenance, emergence, or recovery from anesthesia may improve patient safety.

PMID- 15983455
TI  - Anaphylactic shock: a form of distributive shock without inhibition of oxygen
      consumption.
AB  - BACKGROUND: The pathophysiology of anaphylactic shock during anesthesia is
      incompletely characterized. It is described as distributive by analogy with
      septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values).
      The Ptio2 profile and its metabolic consequences during anaphylaxis are not
      known. METHODS: Ovalbumin-sensitized anaphylactic shock rats (n = 11) were
      compared to nicardipine-induced hypotension rats (n = 12) for systemic
      hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood
      flow, and interstitial lactate and pyruvate concentrations using combined
      microdialysis and polarographic Clark-type oxygen probes. RESULTS: In both
      groups, the time course and the magnitude of arterial hypotension were similar.
      The ovalbumin group but not the nicardipine group displayed decreased skeletal
      muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x
      100 g(-1) x min(-1); P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P <
      0.0001). The ovalbumin group had more intense sympathetic nervous system
      activation with higher plasma epinephrine and interstitial norepinephrine
      concentrations. For the ovalbumin group, there was skeletal muscle anaerobic
      metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/-
      0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased
      from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased
      interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05).
      CONCLUSIONS: This profile suggests decreased skeletal muscle blood flow and
      oxygen delivery. Persistent energy consumption results in decreased Ptio2 and
      substrate depletion through anaerobic glycolysis leading to complete failure of
      cellular energy production. This could explain rapid organ dysfunction and
      resuscitation difficulties.

PMID- 15983456
TI  - Sevoflurane depresses glutamatergic neurotransmission to brainstem inspiratory
      premotor neurons but not postsynaptic receptor function in a decerebrate dog
      model.
AB  - BACKGROUND: Inspiratory bulbospinal neurons in the caudal ventral medulla are
      premotor neurons that drive motoneurons, which innervate pump muscles such as the
      diaphragm and external intercostals. Excitatory drive to these neurons is
      mediated by N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA) receptors and is modulated by an inhibitory
      gamma-aminobutyric acid type A (GABAA)ergic input. The authors investigated the
      effect of sevoflurane on these synaptic mechanisms in decerebrate dogs. METHODS:
      Studies were performed in decerebrate, vagotomized, paralyzed, and mechanically
      ventilated dogs during hypercapnic hyperoxia. The effect of 1 minimum alveolar
      concentration sevoflurane on extracellularly recorded activity of single neurons
      was measured during localized picoejection of the GABAA receptor blocker
      bicuculline and the glutamate agonists AMPA and NMDA. Complete blockade of the
      GABAAergic mechanism by bicuculline allowed differentiation between the effects
      of sevoflurane on overall GABAAergic inhibition and on overall glutamatergic
      excitation. The neuronal responses to exogenous AMPA and NMDA were used to
      estimate the anesthetic effect on postsynaptic glutamatergic neurotransmission.
      RESULTS: One minimum alveolar concentration sevoflurane depressed the spontaneous
      activity of 23 inspiratory premotor neurons by (mean +/- SD) 30.0 +/- 21.0% (P <
      0.001). Overall glutamatergic excitation was depressed 19.2 +/- 18.5% (P <
      0.001), whereas overall GABAAergic inhibition was enhanced by 11.9 +/- 25.1% (P <
      0.05). The postsynaptic responses to exogenous AMPA and NMDA did not change.
      CONCLUSION: One minimum alveolar concentration depressed the activity of
      inspiratory premotor neurons by a reduction of glutamatergic excitation and an
      increase in overall inhibition. The postsynaptic AMPA and NMDA receptor response
      was unchanged. These findings contrast with studies in inspiratory premotor
      neurons where halothane did not change overall inhibition but significantly
      reduced the postsynaptic glutamate receptor response.

PMID- 15983457
TI  - Sevoflurane enhances gamma-aminobutyric acid type A receptor function and overall
      inhibition of inspiratory premotor neurons in a decerebrate dog model.
AB  - BACKGROUND: Inspiratory premotor neurons in the caudal ventral medulla relay
      excitatory drive to phrenic and inspiratory intercostal motoneurons in the spinal
      cord. These neurons are subject to tonic gamma-aminobutyric acid type A
      (GABAA)ergic inhibition. In a previous study, 1 minimum alveolar concentration
      (MAC) sevoflurane depressed overall glutamatergic excitatory drive and enhanced
      overall GABAAergic inhibitory drive to the neurons. This study investigated in
      further detail the effects of sevoflurane on GABAAergic inhibition by examining
      postsynaptic GABAA receptor activity in these neurons. METHODS: Studies were
      performed in decerebrate, vagotomized, paralyzed, and mechanically ventilated
      dogs during hypercapnic hyperoxia. The effect of 1 MAC sevoflurane on
      extracellularly recorded neuronal activity was measured during localized
      picoejection of the GABAA receptor antagonist bicuculline and the GABAA agonist
      muscimol. Complete blockade of GABAAergic inhibition by bicuculline allowed
      estimation of the prevailing overall inhibition of the neuron. The neuronal
      response to muscimol was used to assess the anesthetic effect on the postsynaptic
      GABAA receptor function. RESULTS: One MAC sevoflurane depressed the spontaneous
      activity of 21 inspiratory premotor neurons by (mean +/- SD) 32.6 +/- 20.5% (P <
      0.001). Overall excitatory drive was depressed 17.9 +/- 19.8% (P < 0.01). Overall
      GABAAergic inhibition was enhanced by 18.5 +/- 18.2% (P < 0.001), and the
      postsynaptic GABAA receptor function was increased by 184.4 +/- 121.8% (n = 20; P
      < 0.001). CONCLUSION: One MAC sevoflurane greatly enhanced GABAA receptor
      function on inspiratory premotor neurons and increased overall synaptic
      inhibition but to a smaller extent, indicating that the presynaptic inhibitory
      input was also reduced. Therefore, the anesthetic depression of spontaneous
      inspiratory premotor neuronal activity by 1 MAC sevoflurane in vivo is due to a
      combined effect on the two major ionotropic synaptic neurotransmitter systems
      with a decrease in overall glutamatergic excitation and a strong enhancement of
      postsynaptic GABAA receptor function.

PMID- 15983458
TI  - Pyruvate modulates hepatic mitochondrial functions and reduces apoptosis
      indicators during hemorrhagic shock in rats.
AB  - BACKGROUND: Dysfunctional mitochondria have been widely accepted as one of the
      key targets and a mediator of secondary cell injury and organ failure during
      hemorrhagic shock (HS). The liver is known to be the first organ to display the
      signs of injury during HS. This report describes experiments to determine whether
      modulation of hepatic mitochondrial dysfunctions by pharmacologic agents could
      prevent liver injury in rats subjected to HS. METHODS: In this study, Sprague
      Dawley rats were either treated as controls or subjected to computer-controlled
      arterial hemorrhage (40 mmHg) for 60 min followed by resuscitation with
      hypertonic saline, hypertonic beta-hydroxybutyrate, or hypertonic sodium pyruvate
      for the next 60 min before death. During the course of the experiment, animals
      were continuously monitored for hemodynamic and metabolic parameters. At the end
      of the experiment, the liver was excised and examined for oxidative injury,
      mitochondrial functions, expression of nitric oxide synthase, and indicators of
      apoptosis. RESULTS: In comparison to hypertonic saline and hypertonic beta
      hydroxybutyrate, pyruvate significantly protected the liver from oxidative
      injury, prevented the up-regulation of nitric oxide synthase, inhibited pyruvate
      dehydrogenase deactivation, and improved cellular energy charge and mitochondrial
      functions. In addition, pyruvate also reduced cleavage of poly-adenosine
      diphosphate ribose polymerase by preventing leakage of mitochondrial cytochrome c
      in the liver of HS animals. CONCLUSIONS: These data suggest that modulation of
      mitochondrial metabolic functions is likely to be one of the important mechanisms
      by which pyruvate exerts its protective effects on the liver during HS and
      resuscitation in rats.

PMID- 15983459
TI  - Role of endothelial nitric oxide synthase as a trigger and mediator of isoflurane
      induced delayed preconditioning in rabbit myocardium.
AB  - BACKGROUND: Isoflurane produces delayed preconditioning in vivo. The authors
      tested the hypothesis that endothelial, inducible, or neuronal nitric oxide
      synthase (NOS) is a trigger or mediator of this protective effect. METHODS: In
      the absence or presence of exposure to isoflurane (1.0 minimum alveolar
      concentration) 24 h before experimentation, pentobarbital-anesthetized rabbits (n
      = 128) instrumented for hemodynamic measurement received 0.9% saline (control),
      the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (10 mg/kg), one of
      two of the selective inducible NOS antagonists aminoguanidine (300 mg/kg) or
      1400W (0.5 mg/kg), or the selective neuronal NOS inhibitor 7-nitroindazole (50
      mg/kg) administered before exposure to isoflurane (trigger; day 1) or left
      anterior descending coronary artery occlusion (mediator; day 2). All rabbits
      underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Tissue
      samples for reverse-transcription polymerase chain reaction and
      immunohistochemistry were also obtained in the presence or absence of N-nitro-l
      arginine methyl ester with or without isoflurane pretreatment. RESULTS:
      Isoflurane significantly (P < 0.05) reduced infarct size (23 +/- 5% [mean +/- SD]
      of the left ventricular area at risk; triphenyltetrazolium chloride staining) as
      compared with control (42 +/- 7%). N-nitro-l-arginine methyl ester administered
      before isoflurane or coronary occlusion abolished protection (49 +/- 7 and 43 +/-
      10%, respectively). Aminoguanidine, 1400W, and 7-nitroindazole did not alter
      infarct size or affect isoflurane-induced delayed preconditioning. Isoflurane
      increased endothelial but not inducible NOS messenger RNA transcription and
      protein translation immediately and 24 h after administration of the volatile
      agent. Pretreatment with N-nitro-l-arginine methyl ester attenuated isoflurane
      induced increases in endothelial NOS expression. CONCLUSIONS: The results suggest
      that endothelial NOS but not inducible or neuronal NOS is a trigger and mediator
      of delayed preconditioning by isoflurane in vivo.

PMID- 15983460
TI  - Neuroprotective effect of epidural electrical stimulation against ischemic spinal
      cord injury in rats: electrical preconditioning.
AB  - BACKGROUND: Electroconvulsion therapy is likely to serve as an effective
      preconditioning stimulus for inducing tolerance to ischemic brain injury. The
      current study examines whether electrical stimuli on the spinal cord is also
      capable of inducing tolerance to ischemic spinal cord injury by transient aortic
      occlusion. METHODS: Spinal cord ischemia was induced by occlusion of the
      descending thoracic aorta in combination with maintaining systemic hypotension
      (40 mmHg) during the procedure. Animals implanted with epidural electrodes were
      divided into four groups according to electrical stimulation and sham. Two groups
      consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC
      group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that
      underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion
      24 h after either pretreatment with epidural electrical stimulation (DE group, n
      = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of
      spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or
      sham stimulation. The group P50 represents the duration of spinal cord ischemia
      associated with 50% probability of resultant paraplegia. RESULTS: Pretreatment
      with electrical stimulation in the DE group but not the RE group protected the
      spinal cord against ischemia, and this stimulation prolonged the P50 by
      approximately 15.0% in the DE group compared with the DC group. CONCLUSIONS:
      Although the optimal setting for this electrical preconditioning should be
      determined in future studies, the results suggest that epidural electrical
      stimulation will be a useful approach to provide spinal protection against
      ischemia.

PMID- 15983461
TI  - Differential inhibition of neuronal Na+-Ca2+ exchange versus store-operated Ca2+
      channels by volatile anesthetics in pheochromocytoma (PC12) cells.
AB  - BACKGROUND: Ca2+ influx is a key component of neuronal intracellular Ca2+
      ([Ca2+]i) regulation. The authors hypothesized that volatile anesthetic
      inhibition of neuronal activity is mediated by inhibition of Ca2+ influx via two
      major mechanisms: plasma membrane Na+-Ca2+ exchange (NCX) and the novel mechanism
      of Ca2+ influx triggered by endoplasmic reticulum Ca2+ depletion (store-operated
      Ca2+ channels [SOCCs]). METHODS: Differentiated rat pheochromocytoma cells loaded
      with the Ca2+ indicator fura-2 were Na+-loaded with 0 Ca2+, 145 mm Na+ Tyrode's
      and 5 microm cyclopiazonic acid plus 10 microm ryanodine (functionally isolating
      plasma membrane). Influx-mode NCX was rapidly reactivated by 0 Na+ and 2.5 mm
      Ca2+. The protocol was repeated in the presence of volatile anesthetics (0.5-1.5
      minimum alveolar concentration [MAC] halothane, isoflurane, or sevoflurane) or
      other drugs to characterize NCX. To examine SOCCs, endoplasmic reticulum Ca2+ was
      depleted by cyclopiazonic acid in 0 extracellular Ca2+, and Ca2+ influx was
      triggered by rapid reintroduction of extracellular Ca2+. The protocol was
      repeated in the presence of anesthetics or other drugs to characterize SOCCs.
      RESULTS: Influx via NCX was not inhibited by voltage-gated Ca2+ channel blockers
      but was sensitive to NCX inhibitors. Halothane and isoflurane (0.5-1.5 MAC)
      significantly inhibited NCX (P < 0.05; paired comparisons), whereas sevoflurane
      at less than 1.5 MAC did not inhibit NCX. SOCC-mediated Ca2+ influx was
      insensitive to a variety of Ca2+ channel blockers but was inhibited by Ni2+. Such
      influx was sensitive only to halothane at greater than 1 MAC but not isoflurane
      or sevoflurane. CONCLUSIONS: These data indicate that volatile anesthetics,
      especially halothane and isoflurane, interfere with neuronal [Ca2+]i regulation
      by inhibiting NCX but not SOCC-mediated Ca2+ influx (except high concentrations
      of halothane).

PMID- 15983462
TI  - Local anesthetic interaction with human ether-a-go-go-related gene (HERG)
      channels: role of aromatic amino acids Y652 and F656.
AB  - BACKGROUND: Human ether-a-go-go-related gene (HERG) potassium channels constitute
      a potential target involved in cardiotoxic side effects of amino-amide local
      anesthetics. The molecular interaction site of these low-affinity blockers with
      HERG channels is currently unknown. The aim of this study was to determine the
      effect of the mutations Y652A and F656A in the putative drug binding region of
      HERG on the inhibition by bupivacaine, ropivacaine, and mepivacaine. METHODS: The
      authors examined the inhibition of wild-type and mutant HERG channels,
      transiently expressed in Chinese hamster ovary cells by bupivacaine, ropivacaine,
      and mepivacaine. Whole cell patch clamp recordings were performed at room
      temperature. RESULTS: Inhibition of HERG wild-type and mutant channels by the
      different local anesthetics was concentration dependent, stereoselective, and
      reversible. The sensitivity decreased in the order bupivacaine > ropivacaine >
      mepivacaine for wild-type and mutant channels. The mutant channels were
      approximately 4-30 times less sensitive to the inhibitory action of the different
      local anesthetics than the wild-type channel. The concentration-response data
      were described by Hill functions (bupivacaine: wild-type IC50 = 22 +/- 2 microm,
      n = 38; Y652A IC50 = 95 +/- 5 microm, n = 31). The mutations resulted in a change
      of the stereoselectivity of HERG channel block by ropivacaine. The potency of the
      local anesthetics to inhibit wild-type and mutant channels correlated with the
      lipophilicity of the drug (r > 0.9). CONCLUSIONS: These results indicate that
      local anesthetics specifically but not exclusively interact with the aromatic
      residues Y652 and F656 in S6 of HERG channels.

PMID- 15983463
TI  - Reduction of postincisional allodynia by subcutaneous bupivacaine: findings with
      a new model in the hairy skin of the rat.
AB  - BACKGROUND: An incision of hairy skin of the rat's back provides a new model for
      postincisional pain to determine the importance of cutaneous anesthesia. METHODS:
      Male Sprague-Dawley rats were anesthetized with sevoflurane and given a 0.6-ml
      subcutaneous injection of bupivacaine (0.25%) under the incision site or the
      medial lumbar dorsum or at the nuchal midline, 30 min before a 1.0-cm skin
      incision. Mechanical stimuli (von Frey hairs, 18-250 mN) were applied to measure
      nociception, indicated by twitching of local subcutaneous muscles, the cutaneus
      trunci muscle reflex. A graded response score, averaging the twitches weighted by
      their vigor, or a population response score, measuring the fraction of rats that
      showed any response, was assessed for 3 days before and over 7 days after
      incision. von Frey hairs were applied 0.5 cm from the incision to test primary
      hyperalgesia and 2.0 cm contralateral to the incision for secondary hyperalgesia.
      RESULTS: Incision induced responses to stimuli that had no effect on intact skin
      (allodynia) and also enhanced responses to forces that normally gave less than
      the full reflex (hyperalgesia). Hyperalgesia was present 30 min after surgery,
      peaked at 3-6 h, and persisted through the week; allodynia had a similar onset
      but was briefer. Both changes were transiently reversed by subcutaneous morphine
      (2.5 mg/kg intraperitoneal). Subcutaneous bupivacaine (0.25%), injected
      preoperatively at the incision site and anesthetizing skin for 2-3 h, suppressed
      primary allodynia for 1 week but had no effect on hyperalgesia. Secondary
      allodynia was obliterated, and secondary hyperalgesia attenuated by this
      treatment. Bupivacaine injected subcutaneously at the nuchal midline before
      surgery was also effective in abbreviating primary and secondary allodynia, with
      no signs of sedation, ataxia, or preconvulsive behavior. CONCLUSIONS: Incision of
      rat hairy skin changes pain responses, similar to pain in humans. Preincisional
      subcutaneous bupivacaine selectively suppresses and shortens allodynia for times
      far outlasting its local anesthesia, an effect largely from systemic actions.

PMID- 15983464
TI  - A comparative study of sequential epidural bolus technique and continuous
      epidural infusion.
AB  - BACKGROUND: In this randomized, double-blind study, the authors compared the
      effectiveness of a sequential epidural bolus (SEB) technique versus a standard
      continuous epidural infusion (CEI) technique of local anesthetic delivery. Both
      techniques used the same hourly dose of local anesthetic. METHODS: Sixteen
      gynecologic patients undergoing abdominal surgery received postoperative epidural
      analgesia using 0.75% ropivacaine at a dose of 22.5 mg (3 ml) per hour. Patients
      were randomly assigned to one of two groups. In the SEB group (n = 8), patients
      received one third of the hourly dose every 20 min as a bolus. In the CEI group
      (n = 8), the hourly dose was administered as a continuous infusion. Analgesia was
      assessed by rest pain scored by a visual analog scale and pinprick to determine
      the number of separately blocked spinal segments on each side of the body. Doses
      of rescue medication for pain were also recorded. RESULTS: The median number of
      blocked spinal segments was 19.5 (range, 18-24) in the SEB group and 11.5 (range,
      10-18) in the CEI group (P < 0.001). The median difference in the number of
      blocked segments between the right and left sides was 0 (range, 0-1) in the SEB
      group and 2 (range, 0-6) in the CEI group (P < 0.04). No patients in the SEB
      group but one patient in the CEI group required rescue medication for pain. The
      visual analog scale pain score was 0 in both groups except for one patient in the
      CEI group during the study period. CONCLUSION: The SEB technique with ropivacaine
      provides superior epidural block compared with an identical hourly dose
      administered as a continuous infusion.

PMID- 15983465
TI  - Alfentanil and placebo analgesia: no sex differences detected in models of
      experimental pain.
AB  - BACKGROUND: To assess whether patient sex contributes to the interindividual
      variability in alfentanil analgesic sensitivity, the authors compared male and
      female subjects for pain sensitivity after alfentanil using a pharmacokinetic
      pharmacodynamic modeling approach. METHODS: Healthy volunteers received a 30-min
      alfentanil or placebo infusion on two occasions. Analgesia was measured during
      the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation
      (eight men and eight women) of increasing intensity or using visual analog scale
      scores during treatment with noxious thermal heat (five men and five women).
      Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic
      models were applied to the analgesia and sedation data using NONMEM. For
      electrical pain, the placebo and alfentanil models were combined post hoc.
      RESULTS: Alfentanil and placebo analgesic responses did not differ between sexes.
      The placebo effect was successfully incorporated into the alfentanil
      pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency
      of alfentanil. However, the placebo effect did not contribute to the analgesic
      response variability. The pharmacokinetic-pharmacodynamic analysis of the
      electrical and heat pain data yielded similar values for the potency parameter,
      but the blood-effect site equilibration half-life was significantly longer for
      electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min).
      CONCLUSIONS: In contrast to the ample literature demonstrating sex differences in
      morphine analgesia, neither sex nor subject expectation (i.e., placebo)
      contributes to the large between-subject response variability with alfentanil
      analgesia. The difference in alfentanil analgesia onset and offset between pain
      tests is discussed.

PMID- 15983466
TI  - Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: A double-blind, randomized, placebo-controlled 3-week study evaluated
      the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both
      in treating patients with neuropathic pain. METHODS: Ninety-two patients with
      diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic
      neuropathic pain with allodynia, hyperalgesia, or pinprick hypesthesia were
      randomly assigned to receive one of four creams (placebo, 2% amitriptyline, 1%
      ketamine, or 2% amitriptyline-1% ketamine combined). The primary outcome measure
      was change in average daily pain intensity (baseline week vs. final week) using
      an 11-point numerical pain rating scale. Secondary outcomes included the McGill
      Pain Questionnaire, measures of allodynia and hyperalgesia, and patient
      satisfaction. RESULTS: A reduction in pain scores of 1.1-1.5 units was observed
      in all groups, and there was no difference between groups. Blood concentrations
      revealed no significant systemic absorption. Minimal side effects were
      encountered. CONCLUSION: This randomized, placebo-controlled trial examining
      topical 2% amitriptyline, 1% ketamine, and a combination in the treatment of
      neuropathic pain revealed no difference between groups. Optimization of doses may
      be required, because another study has revealed that higher concentrations of
      these agents combined do produce significant analgesia.

PMID- 15983467
TI  - Remifentanil-induced postoperative hyperalgesia and its prevention with small
      dose ketamine.
AB  - BACKGROUND: Remifentanil-induced secondary hyperalgesia has been documented
      experimentally in both animals and healthy human volunteers, but never
      clinically. This study tested the hypotheses that increased pain sensitivity
      assessed by periincisional allodynia and hyperalgesia can occur after relatively
      large-dose intraoperative remifentanil and that small-dose ketamine prevents this
      hyperalgesia. METHODS: Seventy-five patients undergoing major abdominal surgery
      were randomly assigned to receive (1) intraoperative remifentanil at 0.05 microg
      x kg(-1) x min(-1) (small-dose remifentanil); (2) intraoperative remifentanil at
      0.40 microg x kg(-1) x min(-1) (large-dose remifentanil); or (3) intraoperative
      remifentanil at 0.40 microg x kg(-1) x min(-1) and 0.5 mg/kg ketamine just after
      the induction, followed by an intraoperative infusion of 5 microg x kg(-1) x min(
      1) until skin closure and then 2 microg x kg(-1) x min(-1) for 48 h (large-dose
      remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48
      postoperative hours. Quantitative sensory tests, peak expiratory flow measures,
      and cognitive tests were performed at 24 and 48 h. RESULTS: Hyperalgesia to von
      Frey hair stimulation adjacent to the surgical wound and morphine requirements
      were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P
      < 0.01) in the large-dose remifentanil group compared with the other two groups,
      which were comparable. There were no significant differences in pain, pressure
      pain detection threshold with an algometer, peak flow, cognitive tests, or side
      effects. CONCLUSION: A relatively large dose of intraoperative remifentanil
      triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia
      was prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain
      facilitator process.

PMID- 15983468
TI  - Sex- and age-related differences in morphine requirements for postoperative pain
      relief.
AB  - BACKGROUND: Sex-related differences in the perception of pain and susceptibility
      to opioids remain a matter of debate. Intravenous morphine titration used to
      obtain pain relief in the immediate postoperative period is a unique clinical
      model for assessing the effect of sex on reported pain. Because of the wide
      variation in dose requirements for pain management, the authors conducted a
      prospective study in a large population and also assessed the effect of aging.
      METHODS: Intravenous morphine titration was administered as a bolus of 2 (body
      weight <or= 60 kg) or 3 mg (body weight > 60 kg) during the immediate
      postoperative period. The interval between each bolus was 5 min. The visual
      analog pain scale (VAS) threshold required to administer morphine was 30, and
      pain relief was defined as a VAS score of 30 or less. Data are expressed as mean
      +/- SD. RESULTS: Data from 4,317 patients were analyzed; 54% of the patients were
      male, and 46% were female. The mean morphine dose required to obtain pain relief
      was 11.9 +/- 6.8 mg or 0.173 +/- 0.103 mg/kg. Women had a higher initial VAS
      score (74 +/- 19 vs. 71 +/- 19; P < 0.001) and required a greater dose of
      morphine (0.183 +/- 0.111 vs. 0.165 +/- 0.095 mg/kg; P < 0.001). In contrast, no
      significant difference was noted in elderly (aged > 75 yr) patients (0.163 +/-
      0.083 vs. 0.157 +/- 0.085 mg/kg). CONCLUSION: Women experienced more severe
      postoperative pain and required a greater dose (+11%) of morphine than men in the
      immediate postoperative period. This sex-related difference disappeared in
      elderly patients.

PMID- 15983469
TI  - Financial implications of a hospital's specialization in rare physiologically
      complex surgical procedures.
AB  - BACKGROUND: The authors previously identified a hospital that has a unique role
      in its region for surgical care. In children aged 0-2 yr, the hospital performed
      64% of all physiologically complex procedures statewide (>or= 8 American Society
      of Anesthesiologists Relative Value Guide basic units). For all age groups
      combined, 48% of the physiologically complex procedures performed at that
      hospital were rare, defined as < 1/workday statewide. METHODS: The authors tested
      the hypothesis that financially important differences can result from performing
      relatively large numbers of such specialized procedures. Methods were developed
      to compare contribution margin (revenue from facility and professional fees minus
      variable costs) per operating room hour (CM/OR hour) between patient groups and
      different types of surgical procedures. RESULTS: CM/OR hour was significantly
      larger by a financially important amount (> 250 dollars/OR hour) for pediatric
      versus geriatric patients (P <or= 0.002), primarily because of higher
      professional reimbursements, with no difference in hospital reimbursements.
      Unexpectedly, CM/OR hour was also significantly greater by at least 250 dollars
      when a rare procedure was involved (P < 0.001 for all ages combined), primarily
      because of greater hospital reimbursements. For cases involving implant charges
      of 10,000 dollars or greater, overall CM/OR hour was negative because increased
      revenues did not compensate for the high variable costs. CONCLUSIONS: Other
      hospitals can use these methods to perform a similar analysis of the financial
      impact of those patient populations or surgical procedures that are unique to
      their own roles in their regional healthcare systems, and to identify the sources
      of financial losses and gains experienced by the hospital.

PMID- 15983470
TI  - Primer of postoperative pruritus for anesthesiologists.
AB  - Postoperative itching is an important problem in the postoperative care unit.
      Pruritus after surgery may be drug induced (including intrathecal opioids) or
      secondary to a preexisting systemic disease. Mechanisms of itching are complex
      and not completely understood. The purpose of this review is to highlight new
      discoveries in pathways and mechanisms of pruritus and to summarize up-to-date
      knowledge about treatment of itching after surgery. More basic and clinical
      studies are needed to address the effects of drugs on specific receptors and
      improve the treatment of postoperative pruritus.

PMID- 15983471
TI  - From the FDA: what's in a label? A guide for the anesthesia practitioner.

PMID- 15983472
TI  - Practice advisory for the perioperative management of patients with cardiac
      rhythm management devices: pacemakers and implantable cardioverter
      defibrillators: a report by the American Society of Anesthesiologists Task Force
      on Perioperative Management of Patients with Cardiac Rhythm Management Devices.

PMID- 15983473
TI  - The McGill pain questionnaire: from description to measurement.
AB  - On the language of pain. By Ronald Melzack, Warren S. Torgerson. Anesthesiology
      1971; 34:50-9. Reprinted with permission. The purpose of this study was to
      develop new approaches to the problem of describing and measuring pain in human
      subjects. Words used to describe pain were brought together and categorized, and
      an attempt was made to scale them on a common intensity dimension. The data show
      that: 1) there are many words in the English language to describe the varieties
      of pain experience; 2) there is a high level of agreement that the words fall
      into classes and subclasses that represent particular dimensions or properties of
      pain experience; 3) substantial portions of the words have approximately the same
      relative positions on a common intensity scale for people who have widely
      divergent backgrounds. The word lists provide a basis for a questionnaire to
      study the effects of anesthetic and analgesic agents on the experience of pain.

PMID- 15983474
TI  - Isotonic fluid absorption during hysteroscopy resulting in severe hyperchloremic
      acidosis.

PMID- 15983476
TI  - Sickle cell and anesthesia: do not abandon well-established practices without
      evidence.

PMID- 15983477
TI  - Circadian influences, low-dose isoflurane, and the ventilatory response to
      hypoxia.

PMID- 15983478
TI  - Position of the shoulder for subclavian approach.

PMID- 15983482
TI  - Myocardial performance index and tissue Doppler systolic wave velocity are
      preload dependent.

PMID- 15983483
TI  - Transsacrococcygeal ganglion impar block for postherpetic neuralgia.

PMID- 15983485
TI  - Ganglion impar block in noncancer perineal pain: what drugs, what strategy?

PMID- 15983486
TI  - Valve leaks with new disposable extraglottic airway devices.

PMID- 15983487
TI  - Life-threatening ventilatory obstruction due to a defective tracheal tube during
      spinal surgery in the prone position.

PMID- 15983489
TI  - Fatal thrombosis in an adult after thoracoabdominal aneurysm repair with
      aprotinin and deep hypothermic circulatory arrest.

PMID- 15983493
TI  - ASPSN 2005 Strategic Plan.

PMID- 15983494
TI  - Personalizing my own strategic recruitment plan.

PMID- 15983495
TI  - Vacuum assisted closure therapy: a must in plastic surgery.
AB  - Negative pressure wound therapy, available in the United States through Kinetic
      Concepts, Incorporated, San Antonio, Texas, as Vacuum Assisted Closure (VAC)
      therapy, is a must in plastic surgery. VAC therapy and the VAC dressing change
      procedure are described. Benefits of VAC therapy as well as cost concerns are
      discussed.

PMID- 15983496
TI  - A pediatric civil war burn victim: the patient's and caregivers' stress and
      coping.
AB  - A patient's and the caregivers' threats and reliefs during nursing of a pediatric
      civil war burn victim, treated through a charity grant in a Western hospital, are
      discussed and supported by a literature review.

PMID- 15983497
TI  - Understanding hyperbaric oxygen therapy and its use in the treatment of
      compromised skin grafts and flaps.
AB  - Nonhealing wounds represent a problem involving inadequate oxygenation of the
      tissues that can lead to hypoxic injury. Hyperbaric oxygen therapy can be used as
      an adjunctive therapy for compromised grafts and flaps that have failed to show
      improvement with standard wound therapy and offer additional physiologic benefits
      in the reversal of wound hypoxia and hypoperfusion. A literature review confirms
      the efficacy of hyperbaric oxygen therapy in nonhealing wounds and compromised
      skin grafts and flaps. The purpose of this article is to review the role of
      oxygen and physiological effects of hyperbaric oxygen therapy in wound healing
      and to provide an overview of the hyperbaric oxygen therapy experience including
      indications, types of chambers, patient preparation, complications, and treatment
      protocols. This article is intended to provide nurses working in plastic surgery
      the information necessary to consider the benefits that hyperbaric oxygen therapy
      can offer to improve the healing potential of patients with compromised skin
      grafts and flaps.

PMID- 15983499
TI  - Wound dressing categories.

PMID- 15983500
TI  - Managing controlled substances in the office surgical setting.

PMID- 15983501
TI  - Presurgical screening and informed consent.

PMID- 15983502
TI  - Nursing resumes: a distinctive difference.

PMID- 15983503
TI  - New guidelines in statin therapy.

PMID- 15983504
TI  - Surfing the Internet on nonsurgical rejuvenation: focus on dermal fillers and
      botox cosmetic.

PMID- 15983512
TI  - A job well done.

PMID- 15983513
TI  - Great (but realistic) expectations: what ADA can (and can't) do for you.

PMID- 15983514
TI  - Nutritional recommendations for multiple pregnancy.

PMID- 15983515
TI  - Wine--a drink to your health?

PMID- 15983516
TI  - Foodservice employee recognition programs.

PMID- 15983517
TI  - E-cheating: electronic plagiarism.

PMID- 15983518
TI  - The federal case for quality: implications for dietetics practitioners.

PMID- 15983519
TI  - Sugar intake from combined school lunch and competitive food consumption.

PMID- 15983521
TI  - Recommendations for hypoglycemia.

PMID- 15983522
TI  - Balancing unsaturated fatty acids: what's the evidence for cholesterol lowering?

PMID- 15983523
TI  - A diet rich in high-oleic-acid sunflower oil favorably alters low-density
      lipoprotein cholesterol, triglycerides, and factor VII coagulant activity.
AB  - OBJECTIVE: To compare concentrations of factor VII coagulant activity (factor
      VIIc), fibrinogen, plasminogen activator inhibitor-1, and blood lipids on a
      saturated fat-rich diet with one rich in monounsaturated fat. DESIGN: Subjects
      were randomly allocated to two groups. The study design was an ABB/BAA extra
      period crossover. One group consumed a diet rich in saturated fatty acid (SFA)
      with fat making up 20.8% of total energy, for 5 weeks and then one rich in
      monounsaturated fatty acid (MUFA), with fat making up 20.3% of total energy for
      10 weeks. The other group consumed the MUFA diet for 5 weeks followed by the SFA
      diet for 10 weeks. SUBJECTS/SETTING: Men and women aged 35 to 69 years who were
      nonsmokers with no chronic illness and not on any medication were recruited to
      participate. Eighteen subjects were recruited and 15 (5 men, 10 women) completed
      the community-based study. INTERVENTION: Blood was sampled at the beginning and
      end point of each 5-week diet period for analysis of coagulation and fibrinolysis
      factors and blood lipids. Subjects kept 3-day food diaries twice during each of
      the three diet periods and were weighed on each visit for blood collection.
      Analysis of plasma fatty acids was used to indicate dietary compliance. MAIN
      OUTCOME MEASURES: Differences in fasting factor VIIc, fibrinogen, plasminogen
      activator inhibitor-1, insulin, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B, and plasma
      oleic acid levels while receiving the SFA diet vs MUFA diet. STATISTICAL
      ANALYSIS: A general linear model allowing for the ABB/BAA extra-period crossover,
      was used for each of the outcome measures. RESULTS: Factor VIIc was lower on the
      MUFA diet ( P <.05) but fibrinogen and insulin concentrations and plasminogen
      activator inhibitor-1 activity did not differ between diets. Low-density
      lipoprotein cholesterol ( P <.001) and triglyceride ( P <.01) levels were lower
      on the MUFA diet compared with the SFA diet. A significant increase in both
      plasma phospholipid and neutral lipid oleic acid (P <.0001) occurred on the MUFA
      diet. CONCLUSIONS: Substitution of foods rich in saturated fat with foods rich in
      high-oleic-acid sunflower oil and margarine has favorable outcomes on blood
      lipids and factor VIIc. This oil presents another useful source of MUFA for diets
      aimed at prevention of heart disease.

PMID- 15983524
TI  - Balance of unsaturated fatty acids is important to a cholesterol-lowering diet:
      comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease
      risk factors.
AB  - OBJECTIVE: To evaluate the effects of a trans fat-free monounsaturated fatty acid
      rich vegetable oil (NuSun sunflower oil, National Sunflower Association, Bismark,
      ND) that is a good source of polyunsaturated fatty acids (PUFA) and low in
      saturated fatty acids on lipid and lipoprotein levels and oxidative stress.
      DESIGN: A double-blinded, randomized, three period crossover, controlled feeding
      study. SUBJECTS/SETTING: Thirty-one men (n=12) and women (n=19) with moderate
      hypercholesterolemia who were 25 to 64 years of age. INTERVENTION: Experimental
      diets provided 30% fat (olive oil or NuSun sunflower oil contributed one half of
      the total fat), 8.3% vs 7.9% saturated fatty acid, 17.2% vs 14.2% monounsaturated
      fatty acid, and 4.3% vs. 7.7% PUFA (olive oil and NuSun sunflower oil,
      respectively), and 294 mg cholesterol. The control diet was an average American
      diet (34% fat, 11.2% saturated fatty acid, 14.9% monounsaturated fatty acid, 7.8%
      PUFA). Subjects consumed each diet for 4 weeks with a 2-week compliance break
      before crossing over to another diet. MAIN OUTCOME MEASURES: Lipid and
      lipoprotein levels were measured, and measures of oxidative stress, including lag
      time, rate of oxidation, total dienes, and lipid hydroperoxides, were assessed.
      STATISTICAL ANALYSIS: The mixed model procedure was used to test for main effects
      of diet, feeding period, and order of diets. Tukey-Kramer adjusted P values were
      used to determine diet effects. RESULTS: The NuSun sunflower oil diet decreased
      both total and low-density lipoprotein cholesterol levels compared with the
      average American diet and the olive oil diet. There was no effect of the olive
      oil diet compared with the average American diet. Total cholesterol decreased
      4.7% and low-density lipoprotein cholesterol decreased 5.8% on the NuSun
      sunflower oil diet vs the average American diet. There was no effect of the
      experimental diets on triglyceride levels, rate of oxidation, total dienes, lipid
      hydroperoxides, or alpha-tocopherol. Lag time was the longest following the olive
      oil diet and shortest following the NuSun sunflower oil diet. CONCLUSIONS: The
      higher PUFA content appeared to account for the greater total and low-density
      lipoprotein cholesterol lowering and reduction in lag time of the NuSun sunflower
      oil diet. However, the fact that there were no differences in the resulting
      oxidation products suggests there were no adverse effects on low-density
      lipoprotein oxidation. Since PUFAs are important for cholesterol lowering, foods
      that replace saturated fatty acids should include a balance of unsaturated fatty
      acids.

PMID- 15983525
TI  - Structured dietary advice incorporating walnuts achieves optimal fat and energy
      balance in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: A cardioprotective dietary fat profile is recommended for the
      treatment of type 2 diabetes. The clinical feasibility of advice strategies
      targeting specific fatty acid intakes and the extent to which they can be
      achieved by free-living populations needs to be tested. Walnuts, with high n-3
      polyunsaturated fatty acid (PUFA) content, may help optimize fatty acid intakes,
      but regular consumption might increase total fat and energy intakes. This study
      examined whether advice that refers to a total dietary pattern inclusive of
      walnuts would result in low-fat energy-controlled diets with optimal dietary fat
      proportions for patients with type 2 diabetes mellitus. RESEARCH DESIGN AND
      METHODS: A parallel-design, controlled trial was completed by 55 free-living men
      and women with established type 2 diabetes mellitus. Participants were randomly
      assigned to one of three groups: low-fat (general advice), modified low-fat
      (total diet advice using exchange lists to differentiate PUFA-rich foods), walnut
      specific (modified low fat including 30 g walnuts/day). Dietary intakes and
      clinical outcomes were measured at baseline, and at 3 and 6 months. Dietary goals
      were: less than 10% of energy from saturated fat, 7% to 10% of energy from PUFA,
      adequate n-3 PUFA (>or=2.22 g alpha-linolenic acid, >or=0.65 g eicosapentaenoic
      acid [EPA]+docosahexaenoic acid [DHA]) and n-6 to n-3 ratio less than 10. The
      proportion of subjects achieving dietary goals and major food sources of fat were
      determined. RESULTS: At baseline, dietary intakes were not significantly
      different between groups. No group and few individuals (10%) were consuming
      adequate PUFA, with meat the main source of dietary fat (22% total dietary fat).
      At 3 and 6 months, energy and macronutrient intakes were similar among groups.
      The walnut group, however, was the only group to achieve all fatty acid intake
      targets (P <.01), and had the greatest proportion of subjects achieving targets (
      P <.05). Walnuts were the main source of dietary fat (31%) and n-3 PUFA (50%),
      while 350 g oily fish/day provided a further 17% n-3 PUFA consumed by this group.
      CONCLUSIONS: Specific advice for the regular inclusion of walnuts in the context
      of the total diet helps achieve optimal fat intake proportions without adverse
      effects on total fat or energy intakes in patients with type 2 diabetes mellitus.

PMID- 15983526
TI  - Essential fats in walnuts are good for the heart and diabetes.

PMID- 15983527
TI  - Maternal diet and exercise: effects on long-chain polyunsaturated fatty acid
      concentrations in breast milk.
AB  - BACKGROUND: Long-chain polyunsaturated fatty acids (LC-PUFA) are essential for
      infant growth and development. The amount of long-chain PUFA in breast milk
      depends on maternal diet and body stores. Because exercise increases mobilization
      and utilization of fatty acids, maternal activity may also influence the amount
      of LC-PUFA in breast milk. OBJECTIVE: To investigate the effects of exercise on
      alpha-linolenic acid (LNA), linoleic acid (LA), docosahexaenoic acid (DHA),
      eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations in maternal
      plasma and breast milk and to determine if lactating women consume adequate
      amounts of LC-PUFA to compensate for those used for energy during exercise.
      DESIGN: LC-PUFA in plasma and breast milk were measured at 12 weeks postpartum in
      exercising and sedentary women. Dietary intake was recorded for 3 days. A
      subsample of women participated in exercise and rest sessions to examine the
      acute effects of exercise on breast milk LC-PUFA. RESULTS: There were no
      differences in dietary intake between the two groups. Mean intake (+/-standard
      error of the mean) of LA was 11.05+/-1.39 and 9.34+/-0.97 and LNA was 0.96+/-0.12
      and 0.82+/-0.09 g/day by the sedentary and exercise groups, respectively. These
      amounts are close to the Adequate Intakes of LA and LNA for lactation (13 and 1.3
      g/day, respectively). No differences were found in LC-PUFA in plasma and breast
      milk between groups. After 30 minutes of exercise, there was a trend for an
      increase in LA and LNA concentrations in breast milk, with no change in DHA, EPA,
      and AA concentrations. CONCLUSIONS: These results suggest that women consuming
      adequate amounts of LC-PUFA can exercise moderately without decreasing the LC
      PUFA in their breast milk.

PMID- 15983528
TI  - Increasing maternal docosahexaenoic acid levels.

PMID- 15983530
TI  - Association of dietary supplement use with specific micronutrient intakes among
      middle-aged American men and women: the INTERMAP Study.
AB  - OBJECTIVE: To assess dietary supplement use and its association with
      micronutrient intakes and adequacy among 2,195 US men and women aged 40 to 59
      years from eight diverse population samples surveyed by the International
      Population Study on Macronutrients and Blood Pressure. DESIGN: Four 24-hour
      dietary recalls were collected, including information on dietary supplements. The
      Nutrition Data System (NDS) was used for nutrient analyses. Supplements not in
      NDS were classified separately (non-NDS). Intake of non-NDS supplements was
      documented. Participants were classified as not supplement users and supplement
      users, subclassified-due to concerns about nutritional value-as users of NDS
      supplements only (mostly vitamins and minerals) and users of non-NDS supplements
      (eg, botanicals, animal products, and enzymes). To assess effects of supplement
      use on micronutrient intake and adequacy, mean intakes from supplements, foods,
      and foods plus supplements were compared with Dietary Reference Intakes.
      PARTICIPANTS: Two thousand one hundred ninety-five US participants; 1,136 used
      supplements. STATISTICAL ANALYSES: Chi 2 tests, multivariate logistic regression,
      and means were used to assess differences in and factors related to supplement
      use and to determine dietary adequacy. RESULTS: Supplement use was more common
      among women, older participants, more educated participants, and Asian Americans.
      Body mass index and current cigarette smoking were significantly and inversely
      associated with supplement use; past smoking and education were significantly and
      positively associated with supplement use. Intake from foods plus supplements was
      considerably higher than from foods alone for vitamins A, C, and E; niacin;
      folate; and iron. CONCLUSIONS: Supplement use is common among middle-aged
      Americans and sizably increases daily intakes of several micronutrients. These
      data underscore the importance of dietary supplement assessment.

PMID- 15983531
TI  - Dietary influences on peripheral hormones regulating energy intake: potential
      applications for weight management.
AB  - The significant burden of overweight and obesity on our society necessitates the
      development of lifestyle strategies that facilitate successful long-term body
      weight management. Recently, the discovery of novel cellular modulators of the
      brain-gut axis have generated much interest in possible therapeutic manipulation
      of these and other hormones that regulate energy intake. These modulators include
      the enterohormones ghrelin, peptide YY 3-36, and cholecystokinin, and the
      adipocyte-derived hormone leptin. There is some evidence that dietary
      macronutrient composition can influence concentrations of these hormones, which
      could impact sensations of hunger, satiety, and ultimately energy intake. The
      purpose of this review is to provide background information on these four
      peripheral hormones involved in energy intake regulation, to discuss what is
      currently known about their mechanism of action, and to present research findings
      related to the effect of macronutrient composition on concentrations and efficacy
      of these hormones. Potential applications of this information are also discussed.

PMID- 15983533
TI  - Perceived job importance and job performance satisfaction of selected clinical
      nutrition management responsibilities.
AB  - A nationwide survey of clinical nutrition managers was conducted to assess
      perceived importance of selected job responsibilities and perceived performance
      satisfaction of those job responsibilities. A questionnaire was developed to
      achieve the study objectives, validated by an expert panel, and pilot-tested
      prior to data collection. All members of the American Dietetic Association's
      Clinical Nutrition Management dietetic practice group (N=1,668) were asked to
      rate the importance of selected job responsibilities and their satisfaction with
      those responsibilities using Likert-type scales with descriptions. Results
      revealed that clinical nutrition managers perceived all job responsibilities
      listed in the questionnaire to be important (ie, the mean score of each
      responsibility was >3.0 of a 4.0 scale). Respondents rated regulatory-related job
      responsibilities as most important and were most satisfied with their performance
      of these responsibilities. Following regulatory-related responsibilities,
      clinical nutrition managers perceived patient satisfaction and staff retention to
      be more important than other responsibilities. In general, clinical nutrition
      managers were more satisfied with their job performance for job responsibilities
      that they ranked as more important.

PMID- 15983534
TI  - Soy isoflavone and ascorbic acid supplementation alone or in combination
      minimally affect plasma lipid peroxides in healthy postmenopausal women.
AB  - The objective of this study was to assess synergistic antioxidant properties of
      vitamin C and isoflavones. The design was a placebo-controlled crossover trial:
      500 mg vitamin C, 5 mg/kg body weight isoflavones, 500 mg vitamin C plus 5 mg/kg
      body weight isoflavones, or placebo. Total lipid peroxides, plasma vitamin C, and
      blood pressure were measured. Eight of 10 healthy postmenopausal women completed
      the study. A multiple analysis of variance was performed and least-squares
      difference post-hoc test utilized to determine where differences occurred.
      Significance was defined as P <.05. There was a significant reduction in total
      lipid peroxides between baseline and isoflavone treatments (3.22+/-0.72 vs 2.47+/
      0.82 nmol/mL, P <.05). Mean systolic blood pressure was higher during isoflavone
      intervention than placebo (117+/-14 vs 125+/-15 mm Hg, P= .042). Supplementation
      with vitamin C and isoflavones did not produce a synergistic antioxidant effect.
      A slight but significant increase in systolic blood pressure occurred with
      isoflavone supplementation. A larger study should be conducted to fully explore
      the potential interactions between these antioxidants.

PMID- 15983535
TI  - Elderly herbal supplement users less satisfied with medical care than nonusers.
AB  - The purpose of the study was to examine differences between elderly herbal
      supplement users and nonusers with respect to their perceptions of the safety of
      supplements and their satisfaction with current medical care. The researchers
      interviewed 69 elderly persons from congregate meal sites in four Illinois
      counties to assess herbal supplement use, perceptions of herbal supplement
      safety, medical supervision of herbal supplement use, and satisfaction with
      medical care. Two-sample Kolmogorov-Smirnov tests compared both perceived safety
      of herbal supplements and satisfaction with medical care of supplement users and
      nonusers. Herbal supplement users were more likely to perceive supplements as
      safe and to be less satisfied with conventional medical care than nonusers. Some
      elderly persons do not inform physicians that they are using herbal supplements,
      thus increasing the risk for supplement misuse, toxicity, and drug-supplement
      interactions. It is important that physicians, dietetics professionals, and
      pharmacists inquire about and discuss herbal supplement use with elderly
      patients.

PMID- 15983536
TI  - Esophageal injury by apple cider vinegar tablets and subsequent evaluation of
      products.
AB  - Apple cider vinegar products are advertised in the popular press and over the
      Internet for treatment of a variety of conditions. After an adverse event was
      reported to the authors, eight apple cider vinegar tablet products were tested
      for pH, component acid content, and microbial growth. Considerable variability
      was found between the brands in tablet size, pH, component acid content, and
      label claims. Doubt remains as to whether apple cider vinegar was in fact an
      ingredient in the evaluated products. The inconsistency and inaccuracy in
      labeling, recommended dosages, and unsubstantiated health claims make it easy to
      question the quality of the products.

PMID- 15983538
TI  - Putting the "WOW!" in dietetics.

PMID- 15983537
TI  - Comparison of intakes of US Chinese women based on food frequency and 24-hour
      recall data.
AB  - The objective of this cross-sectional study was to compare dietary reports from a
      food frequency questionnaire (FFQ) for US Chinese women with 24-hour recall
      estimates. The subjects were 56 women recruited through organizations in
      Philadelphia's Chinese community. Spearman correlations were used to describe FFQ
      estimates of food servings per month and nutrient intake per day vs estimates
      from three 24-hour recalls over 1 month. On average, women reported at least
      weekly consumption of 28 of 96 FFQ food items. The three most frequently consumed
      were rice (38 times/month), tea (29 times/month), and dark green, leafy
      vegetables (18 times/month). Comparing reported frequencies of the 28 foods to 24
      hour recall estimates, the median Spearman correlation was 0.36. For nutrient
      estimates, correlations were high (r >0.5) for dietary fiber and calcium;
      moderate ( r =0.25 to 0.5) for energy, saturated fat, cholesterol, carbohydrates,
      protein, folic acid, and iron; but poor (r <0.25) for total fat, vitamin C,
      vitamin A, and carotene. These findings provide some assurance of the FFQ's
      adequacy for describing US Chinese women's intake of commonly consumed foods and
      selected nutrients. They also provide a basis for further improvements to, and
      evaluations of, the FFQ.

PMID- 15983541
TI  - Can dietary intervention play a part in the treatment of attention deficit and
      hyperactivity disorder?

PMID- 15983548
TI  - An assay for human hematopoietic stem cells based on transplantation into
      nonobese diabetic recombination activating gene-null perforin-null mice.
AB  - Abstract Nonobese diabetic recombination activating gene-null perforin-null (NOD-
      Rag1 null Prf1 null ) mice, which totally lack mature T and B cells and natural
      killer cell cytotoxic function, survive longer and are easier to breed than NOD
      severe combined immunodeficiency ( scid ) or NOD- scid /beta 2 -microglobulin
      null mice. We have tested the use of NOD- Rag1 null Prf1 null mice as recipients
      in a long-term xenograft assay for human hematopoietic stem cells (HSCs) by
      adopting Yoder and colleagues' method of conditioned newborn mice, with minor
      modifications. Pregnant NOD- Rag1 null Prf1 null dams were treated with busulfan
      22.5 mg/kg. On the day of delivery, the busulfan-exposed pups underwent
      transplantation with 4 to 5 million T cell--depleted human cord blood mononuclear
      cells via the facial vein. At 2 months after transplantation, all 11 transplanted
      mice showed human hematopoietic engraftment in the peripheral blood. At 6 months
      after transplantation, human cells were detected in 5 mice, which showed higher
      than 0.9% human cell engraftment at 2 months. The mean percentage of human CD45 +
      cells in the bone marrow of engrafted mice was 43.9% +/- 36.5% (range, 2.0%
      79.9%). Next, we tested the usefulness of conditioned newborn NOD- Rag1 null Prf1
      null mice for applications to characterize the dye efflux capability and
      phenotypic features of human HSCs. Given that cord blood HSCs have the ability to
      efflux rhodamine 123 (Rho), we attempted transplantations of sorted cells that
      retained a low level (Rho low ) or high level (Rho high ) of Rho. Six-month
      engraftment was found only with the Rho low cells, which contained high
      percentages of CD34 + CD38 - cells and side population cells with Hoechst 33324
      efflux activity. These observations suggest that Rho low cells are highly
      enriched for primitive hematopoietic cells. Accordingly, conditioned newborn NOD-
      Rag1 null Prf1 null mice provide a desirable model for an assay of long-term
      transplantable human HSCs.

PMID- 15983549
TI  - A phase I/II study of mycophenolate mofetil in combination with cyclosporine for
      prophylaxis of acute graft-versus-host disease after myeloablative conditioning
      and allogeneic hematopoietic cell transplantation.
AB  - Abstract In a phase I/II study, the combination of cyclosporine (CSP) and
      mycophenolate mofetil (MMF) was investigated as graft-versus-host disease (GVHD)
      prophylaxis after myeloablative conditioning and hematopoietic cell
      transplantation from an HLA-matched sibling donor. In phase I, 3 groups, each
      with 10 or 11 patients, received MMF (15 mg/kg) from day 0 to day 27 at
      decreasing dose intervals of every 12, 8, and 6 hours to determine a safe and
      effective total daily dose. At the 45 mg/kg/d dosage level, 4 of 11 patients
      developed only grade II GVHD, and a concentration at steady state of mycophenolic
      acid (the active moiety of MMF) consistent with a therapeutic range described for
      solid-organ transplantation was achieved. There was a suggestion of increased
      toxicity without improved efficacy at the 60 mg/kg/d dosage level. Accordingly,
      the 45 mg/kg/d dosage was therefore selected for phase II, and another 15
      patients were added to this group from the phase I study (n=26). The
      concentrations at steady state for this dosage at days 0, 6, 13, 20, and 27 were
      2.73, 3.02, 3.20, 2.62, and 2.64 microg/mL, respectively. No toxicities were
      attributed to MMF at this dose. The median time to engraftment after
      hematopoietic cell transplantation was 15 days (range, 10-20 days). The incidence
      of acute GVHD was 62%, which was comparable to a group of historical controls
      receiving CSP and methotrexate (MTX) for GVHD prophylaxis. Although a significant
      improvement in the prevention of GVHD was not suggested, compared with CSP and
      MTX, MMF in combination with CSP could be considered in cases in which MTX is
      contraindicated.

PMID- 15983550
TI  - Chest computed tomography of late invasive aspergillosis after allogeneic
      hematopoietic stem cell transplantation.
AB  - Computed tomography (CT) is a powerful diagnostic tool for invasive aspergillosis
      (IA) after allogeneic stem cell transplantation (allo-SCT); however, little
      information is available concerning CT findings of late IA after allo-SCT. To
      characterize CT findings of late IA, we retrospectively examined medical records
      and high-resolution CT findings of 27 allo-SCT recipients with late IA. Either
      acute or chronic GVHD was diagnosed in 24 patients. All 27 patients were given
      corticosteroids at IA diagnosis. High-resolution CT findings included halo
      (n=12), centrilobular nodules (n=12), ill-defined consolidation (n=13), ground
      glass attenuation (n=8), pleural effusion (n=7), pleural-based consolidation
      (n=4), and cavitation (n=4). CT findings showing centrilobular nodules and either
      halo or cavitation were classified into bronchopneumonia type and angioinvasive
      type, respectively. Angioinvasive-type, bronchopneumonia-type, and combination
      type IA were diagnosed in 11, 8, and 4 patients, respectively. CT findings were
      nonspecific in the other 4 patients. One bronchopneumonia-type case and 2
      angioinvasive-type IA cases were subsequently diagnosed as combination type.
      Although there were no significant differences in patient characteristics between
      the 2 types of IA, bronchopneumonia-type IA had a poorer prognosis than
      angioinvasive IA ( P=.022). Halo is a useful diagnostic marker in late IA as well
      as early IA, and late IA frequently manifests as bronchopneumonia.

PMID- 15983551
TI  - A phase Ib clinical trial of PV701, a milk-derived protein extract, for the
      prevention and treatment of oral mucositis in patients undergoing high-dose BEAM
      chemotherapy.
AB  - Despite the best available agents to prevent mucositis, most patients receiving
      high-dose chemoradiotherapy regimens experience severe mucositis, and new
      therapies are needed. In this study, we evaluated the safety and tolerability of
      a milk-derived growth factor extract (PV701 mouthwash) intended to prevent oral
      mucositis (OM) after carmustine, etoposide, cytosine arabinoside, and melphalan
      (BEAM) chemotherapy. PV701 mouthwash (15 mL x 13.5 mg/mL) was administered 6
      times a day for 12 days, from day--6 to day +5, to patients with lymphoma, who
      were given BEAM on day--6 to day--2, with autologous stem cells infused on day 0.
      Dose de-escalation of PV701 was planned if dose-limiting toxicities occurred. The
      severity and duration of OM, the duration of enteral/parenteral feeding, the
      requirement for intravenous opiates, and admission to intensive care were
      recorded. Outcomes were also compared with those of historical control patients.
      Nine patients received PV701 13.5 mg/mL. PV701 was well tolerated, and no dose
      limiting toxicities were observed. Compared with 89 historical controls, the 9
      PV701-treated patients had significantly less frequent grade 2 or 3 OM ( P=.0006)
      and had grade>or=3 OM for an estimated 5 fewer days ( P=.0003). There was a
      reduction in the need for enteral/parenteral feeding ( P=.012), its duration (
      P=.010), and its frequency ( P=.022) and in the duration of intravenous opiates (
      P=.0006). We conclude that PV701 mouthwash is readily administered with minimal
      side effects at a dose of 1215 mg/d, and further investigation of this agent is
      warranted.

PMID- 15983552
TI  - Toxicity and efficacy of daily dapsone as Pneumocystis jiroveci prophylaxis after
      hematopoietic stem cell transplantation: a case-control study.
AB  - The toxicity and efficacy of dapsone given daily as Pneumocystis jiroveci (PCP)
      prophylaxis in hematopoietic stem cell transplant (HSCT) recipients who cannot
      take trimethoprim-sulfamethoxazole (TMP-SMX) have not been fully evaluated. We
      compared 155 HSCT recipients who received daily dapsone as second-line PCP
      prophylaxis with 310 matched control patients who received TMP-SMX throughout the
      posttransplantation course. Among patients who started dapsone before
      transplantation because of TMP-SMX allergy, there was no difference in the
      transfusion requirement after HSCT when compared with controls. Among patients
      who started dapsone after transplantation, increased red blood cell ( P<.0001)
      and platelet transfusion ( P=.003) requirements were noted compared with
      controls. This effect was, however, limited to patients who were receiving
      dapsone for reasons (mostly neutropenia) other than TMP-SMX allergy. Two of 155
      patients developed PCP, compared with 0 of 310 controls ( P=.11); both patients
      survived. In conclusion, the efficacy of daily dapsone in preventing PCP was
      similar to that observed in patients able to remain on TMP-SMX prophylaxis.
      Dapsone did not seem to cause hematologic toxicity among TMP-SMX--allergic
      patients. The observed higher transfusion need in patients who received dapsone
      for reasons other than TMP-SMX allergy seems mostly due to an underlying
      condition of poor marrow reserve. Further studies are required to establish
      whether the drug has an etiologic role in these situations.

PMID- 15983553
TI  - Quantitative detection and differentiation of human herpesvirus 6 subtypes in
      bone marrow transplant patients by using a single real-time polymerase chain
      reaction assay.
AB  - Human herpesvirus (HHV)--6 infections are ubiquitous, but infection or
      reactivation under immunocompromised conditions, such as bone marrow or solid
      organ transplantation, can often result in serious clinical manifestations. Two
      HHV-6 subtypes are known. Most primary HHV-6 infections are caused by subtype 6B,
      but little information is available about the prevalence, distribution, and
      clinical divergence of 6A and 6B. To study this, we have developed a highly
      sensitive and specific real-time polymerase chain reaction (PCR) assay that can
      detect, quantitate, and reliably differentiate HHV-6A and -6B in clinical
      specimens. Exploiting a single-base variation in the DNA polymerase gene of these
      respective subtypes, we used melting curve analysis for subtype discrimination.
      Moreover, this assay's ability to discriminate HHV-6 subtypes was confirmed by
      PCR/restriction fragment length polymorphism analysis of the HHV-6 large tegument
      protein gene and PCR amplicon size-discrimination analysis of the HHV-6 immediate
      early gene. Using this assay, we present our findings about the prevalence and
      distribution of these subtypes in bone marrow transplant patients. Of 803 plasma
      specimens tested from 353 patients, 136 specimens (17%) from 60 patients were
      determined to be HHV-6 positive. We analyzed these HHV-6--positive patients for
      subtype identification by using our newly developed assay and determined that 58
      patients (97%) were HHV-6B positive and 2 patients (3%) were HHV-6A positive. No
      patient was coinfected with both subtypes. This assay can be a sensitive,
      genotype-specific, rapid method to reliably diagnose life-threatening HHV-6
      infections in immunocompromised patients and can be useful in guiding and
      monitoring specific therapy.

PMID- 15983554
TI  - Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell
      transplantation: incidence and effects on survival.
AB  - Engraftment syndrome (ES) encompasses a constellation of symptoms that occur
      during neutrophil recovery after both autologous and allogeneic hematopoietic
      stem cell transplantation (HCT). Although it is well characterized after
      conventional myeloablative procedures, limited data exist on this complication
      after nonmyeloablative allogeneic HCT. The clinical manifestations, incidence,
      and risk factors associated with ES were investigated in a consecutive series of
      patients undergoing cyclophosphamide/fludarabine-based nonmyeloablative
      allogeneic HCT from a related HLA-compatible donor. Fifteen (10%) of 149 patients
      (median age, 53 years; range, 27-66 years) developed ES; the onset of symptoms
      occurred at a median of 10 days (range, 3-14 days), and they consisted of fever
      (100%), cough (53%), diffuse pulmonary infiltrates (100%), rash (13%), and room
      air hypoxia (87%). ES was more likely to develop in patients who received empiric
      amphotericin formulations after transplant conditioning (Fisher exact test;
      P=.007). In a multivariate analysis, older patient age, female sex, and treatment
      with amphotericin were predictors for the development of ES. Intravenous
      methylprednisolone led to the rapid resolution of ES; however, transplant-related
      mortality was significantly higher (cumulative incidence, 49% versus 16%;
      P=.0005), and median survival was significantly shorter (168 versus 418 days;
      P=.005) in patients with ES compared with non-ES patients. In conclusion, ES
      occurs commonly after cyclophosphamide/fludarabine-based nonmyeloablative
      transplantation and responds rapidly to corticosteroid treatment, but it is
      associated with a higher risk of nonrelapse mortality and with shorter overall
      survival.

PMID- 15983555
TI  - Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell
      transplantation.
AB  - Thrombotic microangiopathy (TMA) may occur after allogeneic hematopoietic stem
      cell transplantation (HSCT) and is related in part to calcineurin inhibitor
      toxicity. We observed a higher-than-expected rate of TMA when calcineurin
      inhibitors were combined with sirolimus. To determine the incidence of and risk
      factors for TMA after HSCT, we performed a retrospective cohort analysis of
      myeloablative allogeneic HSCT recipients between 1997 and 2003. TMA diagnosis
      required the simultaneous occurrence of (1) creatinine increase >2 mg/dL or >50%
      above baseline, (2) schistocytosis, (3) increased lactate dehydrogenase, and (4)
      no evidence of disseminated intravascular coagulopathy. A total of 111 sirolimus
      exposed subjects were compared with 216 nonexposed subjects after HSCT. TMA
      occurred in 10.8% of the sirolimus group and 4.2% in the nonsirolimus group (odds
      ratio, 2.79; P=.03). Sirolimus exposure was associated with TMA earlier than in
      nonsirolimus patients (25 versus 58 days; P=.04). Only the use of sirolimus
      (exact odds ratio, 3.49; P=.02) and grade II to IV acute graft-versus-host
      disease (exact odds ratio, 6.60; P=.0002) were associated with TMA in regression
      analyses. Treatment of TMA varied among affected individuals. Renal recovery was
      complete in 92% of sirolimus-treated patients. Overall survival after TMA
      diagnosis was better for sirolimus subjects than for nonsirolimus subjects (58.3%
      versus 11.1%; P=.02). Sirolimus seems to potentiate the effects of calcineurin
      inhibitors on TMA after HSCT. TMA associated with sirolimus seems reversible and
      has a favorable prognosis when compared with TMA associated with calcineurin
      inhibitors alone. A careful monitoring strategy for TMA should be used with a
      sirolimus-containing graft-versus-host disease prophylaxis regimen.

PMID- 15983556
TI  - Evaluation and automation of hematopoietic chimerism analysis based on real-time
      quantitative polymerase chain reaction.
AB  - Abstract Chimerism analysis is an essential tool in the follow-up of patients
      after allogeneic stem cell transplantation. High-resolution methods for chimerism
      analysis based on real-time quantitative polymerase chain reaction (RQ-PCR) with
      a detection limit of 0.1% marker-specific cells are especially valuable in the
      detection of patient-derived subpopulations for the monitoring of minimal
      residual disease. Using artificial chimeric mixtures of genotypically different
      cells, we optimized and evaluated the intrasample variation, accuracy, and
      detection limit of chimerism analysis based on RQ-PCR of short insertion and
      deletion polymorphisms. Furthermore, automated setup by robot was evaluated. The
      results were accurate, with acceptable intrasample variation at and above 0.1%
      marker-specific cells. The sensitivity was mainly limited by background values.
      Chimerism results based on RQ-PCR were similar to results based on PCR of short
      tandem repeats when samples from recipients of transplants with nonmyeloablative
      conditioning were analyzed. Furthermore, automated setup was feasible in a time-,
      labor-, and reagent-conserving manner.

PMID- 15983557
TI  - Re: Twenty-year follow-up in patients with aplastic anemia given marrow grafts
      from HLA-identical siblings and randomized to receive methotrexate/cyclosporine
      or methotrexate alone for prevention of graft-versus-host disease.

PMID- 15983558
TI  - New definition proposed for stem cell transplants.

PMID- 15983568
TI  - Overcrowding: not just an emergency department issue.

PMID- 15983569
TI  - Starling's curve: a way to conceptualize emergency department overcrowding.

PMID- 15983570
TI  - More on morphine sulfate and furosemide use by EMS and the risks of adverse
      outcome.

PMID- 15983571
TI  - Concept of emergency department pain management at triage applauded.

PMID- 15983574
TI  - A 60-year-old man with stridor, drooling, and "tripoding" following a nasal
      polypectomy.

PMID- 15983575
TI  - Variables predicting trauma patient survival following massive transfusion.
AB  - INTRODUCTION: The literature contains little information regarding demographic or
      transfusion-related factors associated with survival following massive blood
      transfusion in trauma patients. The objective of this study was to describe
      patient, transfusion, and laboratory variables contributing to survival in this
      population during the first and second days after arrival at the hospital. A
      secondary objective was to identify costs associated with massive blood
      transfusion. METHODS: A 7-year, retrospective review of 13,005 consecutive trauma
      patient records yielded a sample of 46 who were transfused with > or =50 units of
      blood products in the first postinjury day. Descriptive statistics were computed
      to describe the sample, transfusion data, and laboratory values. Logistic
      regression was used to predict survival using selected patient characteristics,
      laboratory data, and transfusion characteristics for both the first and second
      days. RESULTS: Overall survival among this group who received massive transfusion
      was 63%. No significant differences were found between survivors and nonsurvivors
      in age, sex, type of trauma, or amount of any of the blood components
      administered on Day 1. Nonsurvivors had higher Injury Severity Scores and shorter
      ICU and hospital lengths of stay. Controlling for other variables, only arterial
      base deficit levels made a significant unique contribution to predicting
      survival. The volume of blood transfused on Day 2 did not contribute to survival
      prediction. The average cost of blood transfusion was more than 49,000 US dollars
      per survivor and 51,000 US dollars per nonsurvivor. CONCLUSION: Defining medical
      futility based solely on the volume of blood products transfused currently is
      unjustified. The search for other early indicators of survival in the trauma
      population must continue.

PMID- 15983576
TI  - Relieving an overcrowded ED and increasing capacity for regional transfers: one
      hospital's bed management strategies.

PMID- 15983577
TI  - Placing emergency department crowding on the decision agenda.

PMID- 15983578
TI  - Implementation of the five-level emergency severity index in a level I trauma
      center emergency department with a three-tiered triage scheme.

PMID- 15983580
TI  - Limitations of the national protocol for sexual assault medical forensic
      examinations.

PMID- 15983581
TI  - An original, standardized, emergency department sexual assault medication order
      sheet.

PMID- 15983583
TI  - Transdermal patches: an unseen risk for harm.

PMID- 15983584
TI  - Avulsion amputation of the hand.

PMID- 15983585
TI  - "Life" at 1:15, "death" at 2:33: the perspective of a new graduate emergency
      nurse.

PMID- 15983586
TI  - Two pediatric cases result in change in ED nurse's practice: routine patient
      education emphasizing common risks and simple precautions.

PMID- 15983588
TI  - An ED orientation/fellowship: an experiment in process-oriented training and
      learning to think like an emergency nurse.

PMID- 15983589
TI  - A 22-year-old man with progressive orthopnea, tachycardia, and a nonproductive
      cough.

PMID- 15983591
TI  - "Muscling in" on state boards of nursing: a report from California.

PMID- 15983590
TI  - Bereavement care: one children's hospital's compassionate plan for parents and
      families.

PMID- 15983592
TI  - Giving bad news gracefully.

PMID- 15983593
TI  - Assessing and planning for triage redesign.

PMID- 15983599
TI  - Sudan: a humanitarian response to a silent genocide: an American nurse's
      perspective.

PMID- 15983601
TI  - Empowerment ends bias.

PMID- 15983604
TI  - Are you a servant leader?

PMID- 15983607
TI  - Check the attitude at the patient's door.

PMID- 15983609
TI  - Who's on the mark? Controversy surrounds EMS pursuit of equal resources, priority
      & focus in Congress.

PMID- 15983610
TI  - 30 of the most innovative new products from EMS today.

PMID- 15983611
TI  - Top 40 billing mistakes to avoid. Improve your collections & your bottom line.

PMID- 15983612
TI  - 10 ways to control errors in EMS. Learning from & preventing mistakes.

PMID- 15983613
TI  - Evolving assessment. A systematic approach to the not-so-elementary assessment of
      respiratory emergencies in infants & young children.

PMID- 15983620
TI  - Interneonatal intensive care unit variation in growth rates and feeding practices
      in healthy moderately premature infants.

PMID- 15983622
TI  - Measurement scale does moderate the association between the serotonin transporter
      gene and trait anxiety: comments on Munafo et al.

PMID- 15983625
TI  - Evidence of association between bipolar disorder and Citron on chromosome 12q24.

PMID- 15983626
TI  - Impact of hormone therapy on acute radiotherapy toxicity in the treatment of
      prostate cancer.
AB  - PURPOSE: To analyze the impact of neoadjuvant hormone therapy (HT) on acute
      gastrointestinal (GI) and genitourinary (GU) toxicity from radiotherapy (RT).
      SCOPE: The toxicity rates of 480 consecutive prostate cancer patients were
      reviewed and compared using the chi2 test. Ordered logit regression analyses were
      performed including the major demographic, disease, and treatment factors.
      Although no reduction in acute GI toxicity from HT use was observed (P=0.067), a
      lower rate of acute GU toxicity was observed (P=0.002). No factor reached
      statistical significance on regression analysis. CONCLUSIONS: Observed toxicity
      rates were similar or lower in patients receiving HT. Thus, increased RT toxicity
      should not be a concern when deciding to add neoadjuvant HT to RT for prostate
      cancer.

PMID- 15983628
TI  - Prostate cancer and consistency of reporting sexual histories in men over age 50.
AB  - We conducted an in-person interview to examine the reliability of reported sexual
      histories among men over age 50 y with and without prostate cancer. Marriage and
      cohabitation were used as memory cues to recall sexual activity. High
      correlations on test-retest for questions evaluating sexual histories suggest
      reliable answers for most factors, and specifically for age at first sexual
      activity, and lifetime number of sexual partners. Low correlations were seen for
      ill-defined and socially undesirable items. These data suggest that men
      consistently report most measures of sexual activity when using marriage and
      cohabitation as memory cues to recall sexual histories.

PMID- 15983627
TI  - Role of transrectal ultrasound guided salvage cryosurgery for recurrent prostate
      carcinoma after radiotherapy.
AB  - Despite improvements in treatment of localized prostate cancer, local recurrence
      remains a significant problem. A total of 46 patients with proven local cancer
      recurrence following external beam radiotherapy entered a prospective clinical
      trial using ultrasound-guided cryosurgery to ablate the residual prostate gland.
      Persistent complications included one urethra-rectal fistula, incontinence (2),
      retention (3), and treatment induced erectile dysfunction (7). Using the PSA
      definitions for biochemical failure as PSA>or=0.3 ng/ml, the Kaplan-Meier plots
      showed the incidence of patients to be free of biochemical recurrence at 51 and
      44% at 1 and 2 y, respectively. For a PSA>or=1.0, the values at 1 and 2 y were 72
      and 58%.

PMID- 15983629
TI  - [Milwaukee shoulder syndrome (apatite associated destructive arthritis):
      therapeutic aspects].
AB  - Milwaukee shoulder is a well defined clinical entity that can be observed in
      particular in older women. It is a destructive arthropathy associated with the
      deposition of calcium pyrophosphate dihydrate crystals, characterized by the
      presence of large amount of synovial fluid and a complete tear of the rotator
      cuff. Clinical features include pain, swelling and progressive functional
      impairment. The first-line treatment include the use of analgesic drugs and
      repeated arthrocentesis followed by intra-articular steroid administration;
      closed-needle tidal irrigation has been reported to be useful. In late phase we
      can observe narrowing of the acromion-humeral and of the gleno-humeral joint and
      progressive degenerative changes at the humeral head, leading to almost complete
      functional impairment. In these cases a surgical approach with total shoulder
      arthroplasty may be considered.

PMID- 15983630
TI  - [Effects of estrogen peripheral metabolism in rheumatoid arthritis].
AB  - It is well known that the immune reactivity is modulated by gender. In fact,
      women show a more effective immune response as well as a more frequent
      development of autoimmune diseases. In particular, 17 beta-estradiol (E2) in
      patients with systemic inflammatory diseases leads to an higher production of IgG
      and IgM in peripheral blood mononucleated cells (PBMC) and the secretion of
      metalloproteinases and IL-6 by synovial fibroblasts. The effect of E2 seems to be
      partially related to its concentration. In fact, at the physiological
      concentration, E2 seems to exert a pro-inflammatory effect, while at
      pharmacological concentrations shows anti-inflammatory effects. Steroid hormones
      can be converted in downstream hormones along defined pathways. The conversion of
      dehydroepiandrosterone (DHEA) in peripheral macrophages leads to the androgen
      production. Subsequently the enzyme aromatase converts androgens in estrogens,
      and its activity is increased by some inflammatory cytokines such as IL-1beta, IL
      6 and TNF-alpha. In the synovial fluids of rheumatoid arthritis (RA) patients the
      levels of estrogens result significantly increased compared with controls,
      showing the consequence of this unbalanced steroid metabolism. Furthermore, the
      metabolism of estrogens leads to some downstream hydroxylated metabolites, that
      are not waste products, but still active molecules in the inflammatory response.
      In fact, it has been found that synovial fluids of RA patients present a
      different ratio of 16-hydroxylated estrogen metabolites/ 2-hydroxylated
      metabolites, confirming that also the unbalanced metabolism of estrogens and not
      only the estrogen concentration seems to be related to the development and
      worsening of rheumatoid arthritis.

PMID- 15983631
TI  - [The impact of vertebral fractures on quality of life in postmenopausal women
      with osteoporosis. Validity of the Italian version of mini-Osteoporosis Quality
      of Life Questionnaire.].
AB  - BACKGROUND: Vertebral fracture is one of the most commonly occurring osteoporotic
      fractures. Vertebral fractures associated with osteoporosis are a major cause of
      pain in elderly people and may hardly affect patient's health-related quality of
      life (HRQOL), making this an important parameter for assessment in these
      patients. Studies comparing the performance of HRQOL instruments in osteoporosis
      are lacking. OBJECTIVES: The purposes of this study were to assess the effect of
      vertebral fractures on health HRQOL in post-menopausal women with osteoporosis
      and to investigate the validity of the Italian version of the mini-Osteoporosis
      Quality of Life Questionnaire (mini-OQOL) in a clinical setting. METHODS:
      Patients were divided into two study groups, according to fracture status:
      vertebral fractures (41 patients) and no vertebral fractures (27 patients).
      Baseline assessments of anthropometric data, medical history, and prevalent
      fracture status were obtained from all participants. All of the participants were
      evaluated using both disease-targeted mini-OQOL and QUALEFFO, generic instrument
      (EUROQoL), disability scale (Roland Morris Disability questionnaire- RMDQ) and
      chronic pain grade questionnaire. RESULTS: Vertebral fractures due to
      osteoporosis significantly decreases scores on physical function, socio-emotional
      status, clinical symptoms, and overall HRQOL. Both disease-targeted
      questionnaires showing an association between the number of prevalent vertebral
      fractures and decreased HRQOL. Significant correlations existed between scores of
      similar domains of mini-OQOL and the QUALEFFO, especially for symptoms, physical
      function, activities of daily living and social function. The receiver operating
      characteristic (ROC) curve analysis of mini-OQOL and the QUALEFFO indicated that
      both questionnaires were significantly predictive of vertebral fractures. Number
      of concomitant diseases presented a weak significant correlation with EUROQoL
      (p=0.041). CONCLUSIONS: Our study suggests that the patients with vertebral
      fractures due to osteoporosis have a relevant impairment in quality of life. Both
      disease-targeted questionnaires discriminated between patients with and without
      vertebral fractures though the mini-OQOL, originally developed to measure the
      effect of vertebral fractures on quality of life, showed slightly better
      discriminant power. The benefit of the mini-OQOL is that it is efficient, self
      administered, and requires 3-4 minutes to complete.

PMID- 15983632
TI  - [Incidence and socioeconomic burden of hip fractures in Italy].
AB  - OBJECTIVES: The aim of this study was to evaluate the trend of the incidence and
      costs of hip fractures in Italy. METHODS: The incidence of hip fractures after 45
      years of age in both females and males during the years 1999-2002 was obtained by
      analyzing the Italian Ministry of Health national hospitalization database,
      according to the diagnosis codes of International Classification of Diseases,
      Clinical Modification, 9th edition (IDC-9-CM) that indicate femoral fracture. We
      have computed all direct costs sustained by the National Health Service for
      hospitalization and treatment of hip fractures on the basis of the value of the
      Diagnosis Related Groups (DRG) referring to hip fractures. The expenses of
      rehabilitation and indirect expenses were based on estimates. RESULTS: In 2002,
      more than 86,000 hip fractures were registered in Italy in male and female
      patients over 45 years old, with 9% progression compared to 1999; 77% were female
      and 80% were over 75 years of age. In 2002 the direct costs of hospitalization,
      in the patients over 65 years alone, were almost 400 million euros, with an
      increase of 15% as compared to 1999. Considering also estimated rehabilitation
      costs, social aid and indirect costs, we estimate that hip fractures due to age
      related osteoporosis created over a billion euros in expenses in 2002.
      CONCLUSIONS: Preventive intervention regarding the risk of hip fracture in
      elderly patients is urgent.

PMID- 15983633
TI  - [Systemic lupus erythematosus: the first Italian prevalence study].
AB  - OBJECTIVES: The aim of the study was the assessment of SLE prevalence in an adult
      population. The study was performed on a sample of more than 30,000 patients over
      18 resident in the Florence sub-area of Scandicci-Le Signe (Italy) on the basis
      of the register of general practitioners (GPs). METHODS: Twenty GPs gave the
      Lupus Screening Questionnaire (LQS) to their patients. The LQS has been completed
      by 32,521 patients resident in Scandicci, Lastra a Signa and Signa area. On the
      basis of the LQS analysis an SLE diagnosis was suspected in 30 patients. These 30
      patients have been investigated by routine exams, anti-nuclear antibodies and
      have been referred to rheumatologist to assess the SLE diagnosis and disease
      activity (ECLAM Score). RESULTS: The overall population aged >18 years was 71,204
      (42,474 living in Scandicci, 15,368 in Lastra a Signa and 13,362 in Signa). The
      diagnosis was confirmed in 23 out of the 30 suspected SLE patients. Eleven out of
      the 23 SLE patients were from Scandicci, 6 from Lastra a Signa and the other 6
      from Signa. The overall rate of SLE prevalence is 71/100,000 (1 case/1,408) with
      a confidence interval of 95%, (confidence limits: 49-92). The rate of SLE
      prevalence in Scandicci is 81/100,000 (confidence limits: 42-121), in Lastra a
      Signa 62/100,000 (confidence limits: 32-92) and in Signa 65/100,000 (confidence
      limits: 36-94). CONCLUSION: This is the first epidemiological study on SLE
      prevalence in Italy. The rate of SLE prevalence is similar to that of other
      European studies. LQS is confirmed as an easy and reliable tool to assess SLE
      diagnosis also in the Italian population.

PMID- 15983634
TI  - [The role of anti-nucleosome antibodies in systemic lupus erythematosus. Results
      of a study of patients with systemic lupus erythematosus and other connective
      tissue diseases].
AB  - OBJECTIVE: The aim of our study was to investigate the prevalence and the disease
      specificity of anti-nucleosome antibodies in systemic lupus erythematosus and
      their association with disease activity and renal involvement. METHODS: Anti
      nucleosome antibodies were measured by ELISA in the sera of patients with
      systemic lupus erythematosus (SLE) (47), rheumatoid arthritis (RA) (22), mixed
      connective tissue disease (MCTD) (19), systemic sclerosis (SSc) (11) and
      Sjogren's syndrome (SS) (10). Anti-dsDNA antibodies were measured by IIF on
      Crithidia luciliae. In the patients with SLE serum levels of C3 and C4 complement
      components were also measured. Sera of 22 healthy individuals were assayed as
      controls. SLE activity was evaluated by the ECLAM score. RESULTS: Anti-nucleosome
      antibodies were found in 40 patients with SLE (85.1%), in 10 with RA (45.4%), in
      8 with MCTD (42.1%), in 4 with SSc (36.3%), in 1 with SS (10%) and in none of the
      healthy controls. Anti-dsDNA antibodies were found in 23 patients with SLE and
      were absent in the patients with other CTD and in controls. All the patients with
      SLE and renal involvement were positive both for anti-dsDNA antibodies and anti
      nucleosome antibodies. No significant correlation was observed between anti
      nucleosome antibodies and disease activity and renal involvement. CONCLUSION:
      Anti-nucleosome antibodies are present in a high percentage of the patients with
      SLE but they don't seem to be specific markers of the disease. Our data don't
      support a clear correlation between anti-nucleosome antibodies and disease
      activity and renal involvement.

PMID- 15983635
TI  - [Pulmonary hypertension in autoimmune rheumatic diseases].
AB  - OBJECTIVE: Pulmonary hypertension is a severe and rapidly progressive disease,
      particularly frequent in patients with rheumatic diseases. The aims of this study
      were the following: to determine the prevalence of pulmonary hypertension in
      Italian patients with autoimmune rheumatic diseases, and to evaluate if the
      presence of a rheumatic disease in general, or of a specific autoimmune rheumatic
      disease, is a risk factor for the development of pulmonary hypertension. PATIENTS
      AND METHODS: One hundred and thirteen Italian patients with connective tissue
      diseases (105 females, 8 males), aged 19 to 83 yrs, entered the study. Fifty-one
      had systemic sclerosis (SSc): 49 were females, 2 males, aged 34 to 83 yrs; 41 had
      limited cutaneous SSc, 8 diffuse cutaneous SSc, and 2 SSc sine scleroderma.
      Thirty-three patients had systemic lupus erythematosus (SLE): all but one were
      females, their age ranged from 19 to 82 yrs. Twenty-five had rheumatoid arthritis
      (RA): 21 females, 4 males, aged 26 to 45 yrs. Three females and one male, 51-77
      yrs, had mixed connective tissue disease (MCTD). Systolic pulmonary arterial
      pressure (SPAP) was assessed by Doppler echocardiography. RESULTS: Twenty three
      patients had pulmonary hypertension, which was more frequent in MCTD than in SLE
      (75% vs 6.1%, p=0.0002) or in AR (20%, p=0.0313). Pulmonary hypertension was more
      frequent in SSc than in SLE (25.5% vs 6.1%, p=0.0028) and in limited than in
      diffuse SSc (21.6% vs 3.9%). SPAP was significantly related to age (r=0.35,
      p=0.0275), with patients with pulmonary hypertension older than patients with
      normal SPAP (66+/-13 vs 52+/-16 yrs, p=0.0003). CONCLUSIONS: These data show a
      significant association between pulmonary hypertension and autoimmune rheumatic
      diseases. Therefore, pulmonary hypertension assessment seems mandatory, at least
      in MCTD and SSc. However, more studies are needed to clarify the relationship
      between age and pulmonary hypertension and to verify whether the low prevalence
      of pulmonary hypertension we found in our SLE patients is related or not to their
      lower age.

PMID- 15983636
TI  - [Efficacy of Carbopol 974P (Siccafluid) in the treatment of severe to moderate
      keratoconjunctivitis sicca in patients with primary Sjogren's syndrome not
      responding to standard treatment with artificial tears].
AB  - OBJECTIVE: To determine efficacy and safety of Carbopol 974P in the treatment of
      severe to moderate keratoconjunctivitis sicca (KCS) in patients with primary
      Sjogren's syndrome (SS) not responding to standard treatment with artificial
      tears. METHODS: 60 patients (57 F, 3 M, mean age 52.5+/-12.0, mean disease
      duration 12.2+/-7.1 yrs) affected with primary SS diagnosed according to the
      European Community Study Group criteria were studied. Foregoing medications for
      SS and artificial tears for KCS have not been changed within 3 and 2 months
      respectively prior to the study onset. In all cases Carbopol 974P was added
      because symptoms of KCS were not adequately controlled with traditional
      lubricants. Schirmer I test, B.U.T. (break up time), rose Bengal-stain, clinical
      ophthalmological examination (i.e. fluorescein staining, keratis, corneal
      infiltrates and ulcers) and a questionnaire for dry eye symptoms (range 0-30)
      were performed at entry (T0) and after 2 (T1) and 12 (T2) weeks. Assessment of
      global efficacy was obtained by VAS 0-100 at T2 either by patients and by the
      ophthalmologist. RESULTS: Lachrymal tests significantly improved after 2 and,
      even more, after 12 weeks. Clinical ophthalmologic picture also ameliorated: a
      remarkable reduction of fluorescein positive lesions was demonstrated from 71.6%
      of the cases at T0 to 38.3% at T2. Total score of symptoms (T0: 16.1+/-7.3)
      dropped to 11.9+/-6.6 (T1) (p=0.000) and then to 6.7+/-5.3 (T2) (p=0.000). Global
      efficacy expressed by patients and physician was 74.8+/-15.9 and 76.6+/-13.0,
      respectively. No adverse events (blurred vision, allergy) were reported
      throughout the study. CONCLUSIONS: Our study seems to demonstrate that addition
      of Carbopol 974P to the traditional therapeutic armamentarium for moderate to
      severe KCS is useful and well accepted in patients with primary SS in which
      management of ocular symptoms is unsatisfactory.

PMID- 15983638
TI  - ["De Arthetica passione" in a XVth century Italian manuscript].
AB  - The author describes a 15th century Italian manuscript by Antonio Cauchoreus
      based on the translation of the treatise "De Arthetica passione" by Antonio
      Guainiero di Pauia. This manuscript, that is in the Capitular Archive of Toledo,
      in keeping with the method of Consilia (analysis of symptoms, definition of the
      cause and diagnosis), presents some practical rules to treat gout, including
      particular herbal remedies.

PMID- 15983637
TI  - Osteoporosis in adult with Marfan syndrome: casuality or causality?
AB  - Marfan syndrome (MFS) is an inherited connective tissue disorder transmitted as
      an autosomal dominant trait. Recent studies indicate that decreased bone mineral
      density (BMD) occurs in the spine, femoral necks and greater trochanters of some
      adults and children with MFS. Since there is uncertainty regarding the BMD status
      of patients with MFS, the authors present a case report on a female patient with
      MFS and alteration of phosphocalcic metabolism.

PMID- 15983639
TI  - Supramolecular electronics; nanowires from self-assembled pi-conjugated systems.
AB  - The conditions required for supramolecular electronics, e.g. nano-sized
      optoelectronic devices, will be illustrated on the basis of the programmed self
      assembly of pi-conjugated systems into individual nanosized wires. Using the
      supramolecular design rules nanowires can be created from almost any polymeric
      and oligomeric pi-conjugated system. In the case of oligomers it is even possible
      to construct individual wires having a uniform diameter of one molecule
      thickness. The construction of wires on a substrate is possible by self-assembly
      in solution or during the deposition. The transfer of the supramolecular stacks
      from solution to a solid support is a very delicate process. A comprehensive
      knowledge of all intermolecular interactions gives rise to controlled transfer of
      pi-conjugated assemblies to specific surfaces. There are a large number of very
      appealing targets that should be reached before supramolecular electronics can
      serve as an attractive alternative in between single molecule electronics and
      bulk devices. Nevertheless, the combination of exciting scientific results and
      intriguing technological challenges creates an interesting future for
      supramolecular electronics.

PMID- 15983640
TI  - Shell-crosslinked nanostructures from amphiphilic AB and ABA block copolymers of
      styrene-alt-(maleic anhydride) and styrene: polymerization, assembly and
      stabilization in one pot.
AB  - Shell-crosslinked nanostructures having unusual rosette morphologies have been
      produced by a simple process from styrene and maleic anhydride.

PMID- 15983641
TI  - Enantioselective segregation in achiral nematic liquid crystals.
AB  - The elusive biaxial nematic liquid crystal phase was recently discovered in a
      family of substituted oxadiazoles. Our investigations of these materials show
      that the achiral biaxial nematic phase can segregate into chiral domains of
      opposite handedness, thereby demonstrating that the liquid-like nematic phase
      exhibits the properties of a conglomerate.

PMID- 15983642
TI  - Diels-Alder addition to fluorinated single walled carbon nanotubes.
AB  - Fluorinated single walled carbon nanotubes (SWNTs) undergo a facile Diels-Alder
      [4 + 2] cycloaddition with a range of dienes resulting in a C ratio substituent
      ratio between 20 ratio 1 to 32 ratio 1; IR, Raman, AFM and (13)C NMR
      characterization are consistent with sidewall functionalization.

PMID- 15983643
TI  - Promotion of host folding during the formation of a taco complex.
AB  - Host folding for the formation of taco complexes can be promoted by introduction
      of additional interactions between the host and guest as shown by enhanced
      associations and X-ray crystal structures.

PMID- 15983644
TI  - Duplex strand formation using alternating copolymers.
AB  - The regular arrangement of complementary diaminopyridine-thymine (DAP-THY) on
      alternating copolymers permits cooperative binding events and the effective
      formation of well-controlled micrometre-scale aggregates.

PMID- 15983645
TI  - Coordination polymers formed in solution and in solvent-free environment.
      Structural transformation due to interstitial solvent removal revealed by X-ray
      powder diffraction.
AB  - The crystal-to-powder transformation induced by solvent removal has been examined
      through a direct comparison of the structures of the solvated and the unsolvated
      coordination products determined by single crystal and powder X-ray diffraction,
      respectively.

PMID- 15983646
TI  - Persistent interactions between hydroxylated nanoballs and atactic poly(2
      hydroxyethyl methacrylate)(PHEMA).
AB  - The incorporation of self-assembled nanoparticles, a.k.a. hydroxylated nanoballs,
      into poly(2-hydroxyethyl methacrylate)(PHEMA) gives rise to a cross-linked
      network/hydrogel with enhanced interfacial interaction, whereas its inclusion in
      poly(methyl methacrylate)(PMMA) results in plasticization.

PMID- 15983647
TI  - The influence of sterics on the formation of polar 1-D hydrogen-bonded networks.
AB  - Polar, noncentrosymmetric packing of directional, 1-D hydrogen-bonded networks of
      chiral, 4-amino-2,6-bis(oxazolinyl)pyridines (ampybox) occurs for isopropyl
      substituted ampybox; in contrast, 1-D networks of methyl-substituted ampybox pack
      in an antiparallel arrangement.

PMID- 15983648
TI  - Discrete dispersion of single-walled carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWNTs) have been effectively wetted and dispersed
      in saturated sodium hydroxide (NaOH) alcohol-water solutions with little surface
      damage or shortening of the tubes; the treated material was dissolvable as
      individual tubes in many common organic solvents.

PMID- 15983649
TI  - Processable stabilizer-free polyaniline nanofiber aqueous colloids.
AB  - Aqueous polyaniline colloids can be readily prepared by purifying polyaniline
      nanofibers and controlling the pH and self-stabilized via electrostatic
      repulsions without the need for any chemical modification or steric stabilizer,
      thus providing a simple and environmentally friendly way to process the
      conducting polymer in its conductive state both in bulk and at the nanometre
      level.

PMID- 15983650
TI  - Efficient optical resolution of secondary alkyl alcohols by chiral supramolecular
      hosts.
AB  - A novel tunable multi-chiral supramolecular host system was developed from non
      chiral dicarboxylic acid and (1R, 2R)-diphenylethylenediamine via chirality
      transfer, which enabled highly efficient optical resolution of secondary alkyl
      alcohols by simple crystallization of host compounds from alcohol solution.

PMID- 15983651
TI  - Facile insertion reaction of arynes into carbon-carbon sigma-bonds.
AB  - The carbon-carbon sigma-bond of various beta-dicarbonyl compounds was found to
      add to the triple bond of arynes under extremely mild conditions, leading to
      direct introduction of different carbon functional groups into the aromatic
      skeletons.

PMID- 15983652
TI  - Rh(I)-catalyzed CO gas-free cyclohydrocarbonylation of alkynes with formaldehyde
      to alpha,beta-butenolides.
AB  - The rhodium(I)-catalyzed reaction of alkynes with formaldehyde proceeds via the
      double incorporation of a carbonyl moiety from formaldehyde, resulting in a CO
      gas-free cyclohydrocarbonylation leading to alpha,beta-butenolides.

PMID- 15983653
TI  - Fine tuning the structure of the Cu2+ complex with the prion protein chicken
      repeat by proline isomerization.
AB  - The interaction between the single hexarepeat unit of chicken prion protein
      [ChPrP(54-59)] and Cu(II) was investigated by NMR, finding different coordination
      modes for the trans/trans and cis/trans isomers.

PMID- 15983654
TI  - The first rare earth organometallic complex of 1,4,7-trithiacyclononane: a
      precursor to unique cationic ethylene and alpha-olefin polymerisation catalysts
      supported by an all-sulfur donor ligand.
AB  - [Sc([9]aneS3)(CH2SiMe3)3], the first rare earth organometallic complex of 1,4,7
      trithiacyclonane, is a precursor to ethylene and alpha-olefin polymerisation
      catalysts upon activation with BAr(F)3 or [CPh3][BAr(F)4](Ar(F) = C6F5); these
      are the first cationic rare earth organometallic catalysts supported by an all
      sulfur donor ligand.

PMID- 15983655
TI  - First osmium-catalysed ketamination of alkenes.
AB  - Conditions for a first oxidative conversion of alkenes into 2-amino ketones are
      described, which yield racemic products within a direct oxidation pathway and 2
      amino ketones with up to 99% enantiomeric excess from the corresponding
      enantiopure amino alcohols.

PMID- 15983656
TI  - A readily prepared neutral heterobimetallic titanium(IV)-rhodium(I) catalyst for
      intramolecular hydroacylation.
AB  - The combination of HOCMe2CH2PPh2, Ti(OiPr)4, and [Rh(cod)Cl]2 (3:1:1) in either
      benzene or dichloromethane produces a discrete species (tentatively formulated as
      complex) that is an active catalyst for intramolecular hydroacylation reactions
      of 3-substituted pentenals.

PMID- 15983658
TI  - Well-defined imidotitanium alkyl cations: agostic interactions, migratory
      insertion vs.[2+2] cycloaddition, and the first structurally authenticated
      AlMe(3) adduct of any transition metal alkyl cation.
AB  - The imidotitanium alkyl cations [Ti(NtBu)(Me3[9]aneN3)R]+ (R = Me (3+) or
      CH2SiMe3(4+)) possess either a very weak alpha-agostic or beta-Si-C agostic
      interactions, respectively, according to 13C and 29Si NMR and DFT studies;
      reaction of (4+) with iPrNCNiPr gives totally selective insertion into the Ti
      alkyl bond; reaction of 3+ with AlMe3 gives the first structurally characterised
      AlMe3 adduct of a transition metal alkyl cation (Me3[9]aneN3 = 1,4,7
      trimethyltriazacyclononane).

PMID- 15983657
TI  - Unprecedented, fully recyclable, solid-supported reagent for the kinetic
      resolution of racemic amines through enantioselective N-acetylation.
AB  - The high-yielding synthesis and application of the first polymer supported
      reagent for the kinetic resolution (KR) of amines through enantioselective
      acetylation is described; this new supported chiral reagent allows the KR of
      primary amines with excellent selectivities at room temperature; moreover, this
      supported approach is highly efficient as the Merrifield-supported chiral
      scaffold can be quantitatively recovered and recycled.

PMID- 15983659
TI  - Synthesis and cellular uptake of cell delivering PNA-peptide conjugates.
AB  - The synthesis and cellular uptake of fluorescently labelled PNA-peptide
      conjugates is described; Dde/Mmt protected PNA monomers, fully orthogonal to Fmoc
      chemistry, were used to develop a flexible strategy to give Peptide Nucleic Acids
      conjugated to tri- and hepta-arginine and the short basic Tat(48-57) peptide as
      examples of cellular penetrating peptides, thereby allowing efficient cellular
      delivery of PNA into cells.

PMID- 15983660
TI  - Polyfunctionalized macrocycles demonstrate enantioselective and ditopic binding
      properties.
AB  - A pair of enantioselective, ditopic macrocycles is described; the receptors bind
      chiral ammonium cations in a manner that depends on the stereochemistry of the
      cation as well as the nature of its counter anion.

PMID- 15983661
TI  - Reversible hydrogen gas uptake in nanoporous Prussian Blue analogues.
AB  - The family of dehydrated nanoporous Prussian Blue analogues,
      M(II)3[Co(III)(CN)6]2 (M(II) = Mn, Fe, Co, Ni, Cu, Zn, Cd), which contain
      coordinatively unsaturated divalent metal cations, undergoes reversible sorption
      of hydrogen gas up to 1.2 wt% (at 77 K, 101.3 kPa), the capacity of which depends
      on the metal ion.

PMID- 15983662
TI  - Poly(ionic liquid)s: a new material with enhanced and fast CO2 absorption.
AB  - Novel sorbent and membrane materials for CO2 separation, poly(ionic liquid)s made
      from ionic liquid monomers, poly[p-vinylbenzyltrimethyl ammonium
      tetrafluoroborate](P[VBTMA][BF4]) and poly[2
      (methacryloyloxy)ethyltrimethylamnonium tetrafluoroborate](P[MATMA][BF4]) have
      absorption capacities 7.6 and 6.0 times of those of room-temperature ionic
      liquids, e.g.[bmim][BF4], respectively, with reversible and fast sorption and
      desorption.

PMID- 15983663
TI  - Enhancement of electrochemical and photoelectrochemical properties of fibrous Zn
      and ZnO electrodes.
AB  - Zinc and zinc oxide electrodes with fibrous morphologies were prepared to exploit
      their high interfacial areas and superior electrical conductivity for the
      enhancement of electrochemical and photoelectrochemical properties.

PMID- 15983664
TI  - A single-site hydroxyapatite-bound zinc catalyst for highly efficient chemical
      fixation of carbon dioxide with epoxides.
AB  - A zinc-based hydroxyapatite catalyst in conjunction with a Lewis base proved to
      be efficient for the coupling of CO2 and epoxide in the absence of additional
      organic solvents under an atmospheric CO2 pressure; the work-up procedure is
      straightforward and the catalyst could be reused without loss of catalytic
      activity and selectivity.

PMID- 15983665
TI  - Thioctic acid amides: convenient tethers for achieving low nonspecific protein
      binding to carbohydrates presented on gold surfaces.
AB  - The thioctic acid amides of 2'-aminoethyl alpha-d-mannopyranoside and 2'
      aminoethyl alpha-1,3-d-mannopyranosyl (alpha-1,6-d-mannopyranosyl)-alpha-d
      mannopyranoside presented on both planar and nanoparticle gold surfaces give
      higher specific and lower non-specific protein binding than the related 2'
      thioethyl glycosides.

PMID- 15983666
TI  - Markedly enhanced recyclability of osmium catalyst in asymmetric dihydroxylation
      reactions by using macroporous resins bearing both residual vinyl groups and
      quaternary ammonium moieties.
AB  - Markedly enhanced recyclability of osmium catalyst in asymmetric dihydroxylation
      has been achieved by using osmylated macroporous resins bearing both residual
      vinyl groups and quaternary ammonium moiety.

PMID- 15983667
TI  - Halogen: a high-capacity cathode for rechargeable alkaline batteries.
AB  - Here we report a new high capacity battery system referred to as RAH batteries,
      which is based upon a high energy cathode-halogen (such as Br2 or Cl2) and metal
      hydride anode.

PMID- 15983668
TI  - Figure-eight aromatic core-modified octaphyrins with six meso links: syntheses
      and structural characterization.
AB  - The synthesis and structural characterization of the first examples of aromatic
      core-modified figure-eight octaphyrins with six meso links and their formation
      with and without acid catalysts are highlighted.

PMID- 15983669
TI  - A high-voltage dye-sensitized photocapacitor of a three-electrode system.
AB  - A high-voltage photo-rechargeable capacitor (photocapacitor) of three-electrode
      configuration, comprising a dye-sensitized mesoporous TiO2 electrode, two carbon
      coated electrodes, and two liquid electrolytes, attained a charge-state voltage
      of 0.8 V and high energy density per area of 47 microW h cm(-2) which is five
      times larger than the previous two-electrode photocapacitor.

PMID- 15983670
TI  - Cp*(iPr3P)Ru(Cl)(eta2-HSiClMe2): the first complex with simultaneous Si-H and
      RuCl...SiCl inter-ligand interactions.
AB  - The addition of HSiMe2Cl to the unsaturated compound Cp*(iPr3P)RuCl gives an
      unstable adduct which, according to NMR (J(H-Si)= 33.5 Hz), X-ray crystal
      structure and DFT evidence, is a silane sigma-complex Cp*(iPr3P)Ru(Cl)(eta2
      HSiMe2Cl) supported by an unprecedented, simultaneous inter-ligand RuCl...SiCl
      hypervalent interaction between the chloride ligand on ruthenium and the SiMe2Cl
      group.

PMID- 15983671
TI  - A new intermediate intercalate in superconducting sodium-doped hafnium nitride
      chloride.
AB  - A new phase has been observed during the sodium intercalation of hafnium nitride
      chloride as intermediate between the host beta-HfNCl and the already reported
      Na(0.29)HfNCl with Tc of 24 K; the new intermediate shows interlayer spacings
      ranging from 9.48 to 9.67 A, corresponds to a second stage intercalate of HfNCl
      and is superconducting with a critical temperature of 20 K.

PMID- 15983672
TI  - Unprecedented eta3-M3 coordination mode in a terpyridine ligand.
AB  - The gold(I) complex [Au3(C6F5)3(eta3-Fcterpy)](Fcterpy = 4'-ferrocenyl
      2,2'ratio6',2''-terpyridine) represents the first example of a terpyridine ligand
      bonded to three different metals. The aurophilic interactions present in the
      molecule may contribute to the overall stability of the system, as was shown by
      DFT calculations. The positive Mayer indices (0.152 and 0.138), as well as the
      magnitude of the binding interaction between terpy and the Au(I)L fragments,
      support this interpretation.

PMID- 15983673
TI  - Epidemiology of type I diabetes mellitus among Arab children.
AB  - In this article, the epidemiology of type 1 diabetes mellitus among Arab children
      (<15 years) living in Arab and non-Arab countries is reviewed. These data include
      the incidence, prevalence and etiopathogenic factors including genetics,
      environmental factors as well as autoimmune disease markers aside from clinical
      presentation at onset. The review is based on the information from publications
      in the international literature identified by searching Medline, other websites
      as well as personal experience and some communications. The obtained data suggest
      that the incidence of type 1 diabetes in these countries is increasing similar to
      the experience in other parts of the world. High incidence has been reported
      among Arab children who immigrated to some Western countries. The highest
      incidence is in Qatar and Kuwait and the lowest is in Oman and Jordan. There is
      considerable variation among countries, which could not be explained on genetic
      or climatic variations alone. Other environmental factors particularly
      nutritional ones including high intake of dairy products and vitamin D deficiency
      are possibly operating. Further, nationwide research from different countries
      covering the rural as well as urban areas and different ethnic intermixes are
      needed. To overcome financial and facility problems that hinder research; some
      cooperation between these countries as well as international bodies are needed.

PMID- 15983674
TI  - Continuous subcutaneous insulin infusion in type 1 diabetic Saudi children. A
      comparison with conventional insulin therapy.
AB  - OBJECTIVE: To assess the efficacy and effectiveness of continuous subcutaneous
      insulin infusion (CSII) therapy in type 1 diabetic Saudi children in comparison
      with conventional insulin (CI) therapy. METHODS: Continuous subcutaneous insulin
      infusion was initiated in 14 Saudi children with type 1 diabetes mellitus (T1DM)
      through insulin pump therapy between October 2002 and June 2004. All children
      were followed at the Diabetes Clinic, King Faisal Specialist Hospital and
      Research Centre, Riyadh, Kingdom of Saudi Arabia. The patients were initially on
      CI therapy, which is usually defined as 2 or fewer insulin injections per day
      before shifting them to CSII. The patients were trained on carbohydrates counting
      and started on continuously basal insulin infusion aside from the meal and high
      blood glucose correction insulin boluses. RESULTS: The patients included in the
      study had T1DM for a mean duration of 6 years. The age of the children ranged
      from 4-18 years. They were followed on insulin pump therapy for a mean duration
      of 10 months. There was a significant reduction in hemoglobin A1c, mean blood
      glucose level, total insulin requirement, frequency of hypoglycemic episodes and
      frequency of diabetic ketoacidosis (DKA) events during CSII therapy. CONCLUSION:
      Continuous subcutaneous insulin infusion improved the glycemic control in
      diabetic Saudi children with decreased frequency of hypoglycemic episodes and DKA
      events. Long follow-up studies are needed to confirm these results.

PMID- 15983675
TI  - Two oestrous cycles. Ten days insulin treatment reduced ovarian leptin expression
      of rat.
AB  - OBJECTIVE: Previous studies have reported a role for insulin in leptin secretion
      from rat ovarian cells although the time dependent effect of insulin has yet to
      be obtained. The study aim is to determine the time dependent effect of insulin
      on leptin staining intensity in the rat ovary. METHODS: Normally cycling rats
      were investigated in a spontaneous cycle (control, n=6), one cycle with insulin
      treatment 2 U/day for 5 days (D5) (n=6), and 2 cycles with insulin treatment 2
      U/day for 10 days (D10) (n=6) in the Department of Histology and Embryology,
      Celal Bayar University, Manisa, Turkey, from May 2004 to August 2004.
      Histological structures and leptin staining of the ovarian cells were
      investigated with immunohistochemical technique and evaluated by a semi
      quantitative scoring system. RESULTS: Number of follicles and stromal cells
      decreased with longer insulin treatment. No leptin staining was observed in
      granulosa cells of all groups. Staining intensity and H-score of the controls, D5
      and D10 groups were (+++)/204, (++)/80 and (+)/9.5 for theca externa cells;
      (+++)/289.5, (++)/126 and (+)/65 for stroma; (++)/140, (++)/70 and (+)/21 for
      corpus luteum. The difference between H-scores of control and D10 groups was
      statistically significant in all tissue types (p<0.01). CONCLUSION: Insulin
      treatment for 10 days (2 estrous cycles) reduced leptin-staining intensity in
      various tissues of the rat ovary and decreased follicle development in a time
      dependent manner.

PMID- 15983676
TI  - Comparative study on apoptosis in the testes of normal and alcoholic rats.
AB  - OBJECTIVES: To investigate the tissue injury associated with long-term alcohol
      consumption in male gonads. To this end, apoptotic testicle tissues of alcoholic
      rats were compared with the testicle tissues of the control rats. METHODS: This
      study was conducted in the Department of Anatomy and Division of Pathology,
      Faculty of Medicine, Kocaeli University, Kocaeli, Turkey during the period 2002
      to 2003. We used Sprague-Dawley rats as the subject material in the investigation
      of apoptosis. We divided the rats into 2 groups: alcoholic rats and the control
      group, with 10 adult male rats in each group. We housed the subjects in each
      group under controlled temperature (22 +/- 3 degrees C) and humidity (62 +/- 7%)
      and lighting (12 hours darkness and 12 hours daylight per day). We fed the rats
      in the alcoholic group by ethanol in liquid diet for 12 weeks while the control
      rats received the normal isocaloric diet. We fixed the testicle tissues of both
      groups by perfusion of 10% formaldehyde through left ventricle and then removed.
      We further fixed the tissues in formaldehyde solution for at least 2 days. After
      dehydration by ethanol, we embedded the tissue in paraffin and used serial
      paraffin sections (5 micron thickness) for immunohistochemistry. We used Caspase
      3 Ab-4 (CPP32) antibody to identify caspase reaction in apoptotic regions. Hence,
      we observed the stained sections and photographed the apoptotic seminiferous
      tubules (ST). For comparison of apoptosis in the alcoholic group and control
      group, we counted the apoptotic germ cells in x 400 magnification under light
      microscope. RESULTS: The diameters of seminiferous tubules were measured using
      light microscope with micrometre. The findings were compared by computer and
      significant differences in apoptosis between 2 groups (p<0.01) were detected.
      CONCLUSION: Apoptosis is significantly induced in ethanol treated rat related to
      the overuse of ethanol. The findings indicate the tissue injury of testicles
      associated with alcohol consumption.

PMID- 15983677
TI  - Effect of pretreatment antistreptokinase antibody and streptococcal infection on
      the efficacy and dosage of streptokinase in acute myocardial infarction.
AB  - OBJECTIVES: The objective of the study is to determine if the presence of
      antistreptokinase (ASK) antibody in the blood, leads to ineffective thrombolytic
      therapy with streptokinase (SK) in acute myocardial infarction (AMI) and to
      investigate if increased dose of streptokinase (2.5 million units) could improve
      the infarct-related artery (IRA) patency or the clinical outcome in these
      patients. METHODS: The study was conducted between 1994 and 2001 in 2
      institutions; King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia and in Kasr
      El-Aini Faculty of Medicine, Cairo, Egypt. Fifty consecutive patients with acute
      myocardial infarction (AMI) were included in this prospective double blind,
      randomized study. All patients were given the allocated streptokinase dose (1.5
      or 2.5 million units) and underwent angiography within 24 hours to establish the
      anatomy of coronary arteries and the patency of infarct-related artery.
      Antistreptokinase antibody assay was carried out in a core laboratory. RESULTS:
      The study results showed that the presence of ASK antibody or the administration
      of an increased dose of SK had no effect on improving the patency rate of the
      infarct-related artery. CONCLUSION: The presence of a previous streptococcal
      infection may not necessarily reduce the effect of SK on the patency of the IRA
      and/or clinical outcome in patients presenting with AMI. The administration of a
      larger than currently recommended dose of SK (2.5 million units) did not alter
      the clinical outcome because it did not improve the patency rate of the IRA.
      However, a larger study is needed to confirm these observations.

PMID- 15983678
TI  - Tissue factor pathway inhibitor, natural coagulation inhibitors and hemostatic
      activation markers in patients with acute coronary syndromes.
AB  - OBJECTIVE: This study aims at characterizing the hemostatic changes, in a large
      cohort of Saudi Arab patients with acute coronary syndromes. METHODS: We
      consecutively enrolled 389 patients (unstable angina [UA]: n=181; myocardial
      infarction [MI]: n=208) in this study at King Khalid University Hospital, Riyadh,
      Kingdom of Saudi Arabia in the period from April 2000 to November 2001. We
      collected blood samples before coronary angiography. Controls (n=101) were
      healthy males and females. All hemostatic assays were undertaken using enzyme
      linked immunosorbent assay based techniques and commercial kits. RESULTS: The
      mean plasma levels of both bound and free tissue factor pathway inhibitors (TFPI)
      were significantly higher and to comparable levels, in patients with MI and UA,
      than in healthy control levels. Markers of thrombin generation: the mean levels
      of prothrombin fraction 1+2, thrombin antithrombin complexes, and D-Dimer were
      very significantly elevated in the 2 patients groups than in controls. Proteins C
      and antithrombin III showed statistically significant reduction especially in
      patients with MI. Plasminogen activator inhibitor levels were significantly
      elevated in the 2 patient groups, but were higher in MI patients. The mean levels
      of fibrinogen and D-Dimer as well thrombin antithrombin complex were higher and
      the levels of free tissue factor pathway inhibitor were lower in patients with 3
      vessel coronary artery disease than those with single and double vessel disease.
      CONCLUSION: The results of this study confirm the existence, and to a similar
      extent, of a hypercoagulable state in Saudi patients with MI than UA and in those
      with 3-vessel coronary artery disease than those with one or 2-vessel disease.

PMID- 15983679
TI  - Postoperative cardiac intensive care outcome for Down syndrome children.
AB  - OBJECTIVE: The purpose of this study is to review the postoperative intensive
      care unit (ICU) course, complications and outcome of Down's syndrome children
      undergoing surgical repair of congenital heart diseases (CHD). METHODS: A
      retrospective chart review analysis of intensive care course and outcome of Down
      syndrome children undergoing surgical repair of congenital heart diseases (CHD)
      from May 2000 to May 2004. The study was conducted in the Pediatric Cardiac ICU,
      King Abdul-Aziz Cardiac Center of National Guard Hospital, Riyadh, Kingdom of
      Saudi Arabia. All Down's syndrome children who had surgical repair during the
      study period were included. RESULTS: During the study period, 80 patients (31
      males and 49 females) with Down's syndrome had surgical repair of CHD. Their
      average weight was 5.8 +/- 0.3 kg and age was 11.7 +/- 1.5 months. Their primary
      surgical interventions were as follow: atrio-ventricular septal defect repair
      (44), ventricular septal defect closure (24), patent ductus arteriosus ligation
      (6), secundum atrial septal defect closure (3), and tetralogy of Fallot repair
      (3). Postoperative complications occurred in 19 patients (23%). Few patients had
      more than one complication. The compilations were as follow: 8 patients (10%) had
      sepsis, 3 (4%) required permanent pacemaker insertion, 4 (5%) had chylothorax, 2
      (2.5%) had life threatening pulmonary hypertensive crisis with full recovery
      after proper managements, 5 (6%) needed prolong intubation, more than 7 days, and
      one patient (1.2%) required tracheostomy. All patients survived and were
      discharged home except one (1.2%) who expired 8 weeks after surgery from sepsis
      and multi-organ failure. CONCLUSION: Patients with Down's syndrome undergoing CHD
      repair had an acceptable postoperative morbidity and low mortality. Their results
      are comparable to non-Down's cardiac patients. From an ICU perspective, the
      majority of these patients do well postoperatively with good ICU outcome.

PMID- 15983680
TI  - The diagonal ear-lobe crease. As sign of some diseases.
AB  - OBJECTIVE: The present study dealt with the question of possible association
      between the diagonal ear lobe crease (ELC) and diabetes mellitus, hypertension,
      myocardial infarction, coronary artery diseases. METHODS: The present study was
      carried out as a field study with the contributions of 6 Primary Health Care
      Centers in Golbasi, Education and Research Area, Ankara, Turkey in May 2003 June
      2003 and includes 3722 individuals (1250 males and 2472 females) of different age
      groups. From each individual, ELC was graded and a thorough medical history was
      taken. RESULTS: Ear lobe creases were found more in males and there was a
      statistically significant positive association between ELC and these diseases in
      both sexes. CONCLUSION: It was thus thought that ELC could well be included as a
      valuable sign in diagnosing and screening such diseases.

PMID- 15983681
TI  - Evaluation of antibacterial activity of aqueous and methanolic extracts of the
      truffle Terfezia claveryi against Pseudomonas aeruginosa.
AB  - OBJECTIVE: To investigate the antibacterial activities of aqueous and methanolic
      extracts, as well as, partially purified proteins extracted from Terfezia
      claveryi aqueous, against Pseudomonas aeruginosa (P. aeruginosa). METHODS: Five
      percent of the aqueous and methanolic extracts were added to growth medium of P.
      aeruginosa. The extract that caused growth inhibition (aqueous) was then
      partially purified using ammonium sulfate precipitation, gel chromatography and
      ion exchange chromatography. Antibacterial activities of the obtained fractions
      were assessed using agar-well diffusion test, and then all the results were
      compared with reference antibiotics. Excremental procedures were performed at the
      Department of Nutrition and Food Technology and the animal house of Jordan
      University of Science and Technology, Jordan during the year 2000. RESULTS: Five
      percent aqueous extract inhibited the growth of P. aeruginosa by 40.9%, while
      methanolic extract was ineffective. Partial purification of the aqueous extract
      using ammonium sulfate precipitation revealed that antimicrobial activity was
      within the second pellet (25-45%). This fraction was then subjected to gel
      permeation chromatography using Sephadex G-25. Peak one, of the 2 peaks obtained,
      possessed higher antimicrobial activity. Peak one was then subjected to ion
      exchange chromatography using DEAE Sephadex. Only peak one, of the 3 peaks
      obtained, showed a slight antimicrobial activity. Relative antimicrobial
      activities of these fractions were found to be superior to most of reference
      antibiotics used for comparison. CONCLUSION: Aqueous extract of the truffle
      Terfezia claveryi contains a potent antimicrobial agent that is protein in nature
      and may be used in the treatment of eye infections caused by P. aeruginosa.

PMID- 15983682
TI  - Extended-spectrum beta-lactamases in urinary isolates of Escherichia coli,
      Klebsiella pneumoniae and other gram-negative bacteria in a hospital in Eastern
      Province, Saudi Arabia.
AB  - OBJECTIVE: To evaluate the prevalence and antimicrobial susceptibility of
      extended spectrum beta-lactamase (ESBL) producing gram-negative organisms
      isolated from patients with urinary tract infection (UTI). METHODS: We carried
      out this study at Almana General Hospital, Eastern Province, Kingdom of Saudi
      Arabia, during the period August 2003 to October 2004. We studied urinary
      isolates of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae),
      Enterobacter spp and Pseudomonas aeruginosa (P. aeruginosa) for ESBL production
      and antimicrobial susceptibility. RESULTS: We studied a total of 2302 urinary
      gram-negative isolates for the presence of ceftazidime resistance and ESBL. The
      isolates included E. coli (1238), K. pneumoniae (522), Enterobacter spp (138) and
      P. aeruginosa (404). Of the 2302 isolates, 232 (10%) were ceftazidime resistant
      and 204 (8.9%) were ESBL producers. We detected ESBL in 119 (9.6%) E. coli, 59
      (11.3%) K. pneumoniae, 14 (10.14%) Enterobacter species and 12 (2.97%) P.
      aeruginosa isolates. The ESBL-producing strains were most commonly isolated from
      patients with indwelling Foley s catheter [131 (64.2%)] and those in the long
      term care ward [90 (44.2%)]. Only 26 (12.7%) ESBL-producing isolates were from
      outpatients. More than 89% of the ESBL producers were susceptible to imipenem and
      meropenem. Amikacin and piperacillin/tazobactam were active against 68% and 45%
      of the isolates. Susceptibility to gentamicin and ciprofloxacin was 22.5% and
      14%. The least active antibiotic was cefepime (11.8%). CONCLUSION: This study
      shows the presence of ESBL producers in uropathogens from both inpatients and
      outpatients and demonstrates their high resistance to various classes of
      antimicrobial agents.

PMID- 15983683
TI  - Identifying futility in a neonatal intensive care unit setting.
AB  - OBJECTIVE: Caring for infants born with lesions that are either incompatible with
      life or conditions that will not allow meaningful survival is an ethical dilemma.
      Provision of intensive ineffective care to these infants may be labeled as
      "futile care" which can consume a major proportion of total hospital expenditure.
      We conducted the present study to look at the extent of futility in a neonatal
      intensive care unit (NICU) setting. METHODS: All neonates with lesion either
      incompatible with life or conditions that will not allow meaningful survival
      admitted during April 2003 to September 2003 in the Neonatal Intensive Care Unit,
      Royal Hospital, Muscat, Sultanate of Oman, were reviewed to identify futility.
      Bed days were used as surrogate for extent of futile care and resource
      consumption. RESULTS: A total of 355 infants were admitted to the NICU during the
      study period representing 4452 consecutive patient bed days. Twenty-five infants
      fulfilled the criteria of futility. Total length of stay of futile group was 317
      (7.1%) days as compared to 4153 (92.8%) days in the non-futile group. CONCLUSION:
      The bed occupancy for futile care cases was less than 8% of all the NICU beds
      suggesting only a small proportion of resource consumption. Based on this,
      expecting cost savings from further limiting futile care in neonates is not
      warranted and is negligible. Ethically, we are assured that the majority of the
      care provided to our sick neonates are appropriate.

PMID- 15983684
TI  - Closure or nonclosure of the peritoneum at gynecological operations. Effect on
      postoperative pain.
AB  - OBJECTIVE: To compare the analgesic requirement and pain scores in the
      postoperative period between closure and nonclosure of the peritoneum in women
      undergoing gynecological abdominal surgery. METHODS: We conducted this study as a
      2 parallel grouped, double blind, randomized, controlled trial between February
      2002 and March 2003. The current study consists of 79 eligible women who were
      enrolled and completed baseline assessments. We carried out this study at the
      Cumhuriyet University Hospital, Sivas, Turkey. RESULTS: When the age, gravidity,
      parity, body mass index, type of surgery, operative time and length of hospital
      stay were compared, between the 2 groups, no statistically significant difference
      was found (p>0.05). The postoperative pain was found higher in the closure group
      than the nonclosure group (p<0.05) when the pain with visual analogue scale (VAS)
      scores compared. CONCLUSION: There was no significant difference in analgesic
      requirements between the 2 groups in the postoperative period. However, less pain
      and low VAS scores were evident especially after postoperative 2nd and 48th hours
      in the nonclosure group. We recommend non-closure of peritoneum at abdominal
      gynecologic procedure as the method of choice.

PMID- 15983685
TI  - Effects of glutamine in critical illness.
AB  - OBJECTIVES: Under normal physiological conditions, glutamine is synthesized in
      large amounts by the human body and is considered nonessential. It has been
      hypothesized that glutamine may become a conditionally essential amino acid in
      patients with catabolic disease. The objective of this study is to investigate
      the prognostic effect of glutamine. METHODS: For this study, we selected 48
      patients from the intensive care unit. Group I consisted of 33 patients whose
      treatment included glutamine. We placed the remaining 15 patients in group II,
      and they did not receive glutamine in their treatment. We retrospectively
      investigated treatment time, leucocyte levels and outcome. We carried out the
      study between January 2002 and January 2003 in Konya Governmental Hospital,
      Turkey. RESULTS: The average duration of hospital stay in the glutamine group was
      8 +/- 1.2 days, 58% of them leaving hospital with surrogate. However, in the
      group whose treatment did not include glutamine, 42% of them left the hospital
      surrogate, their average hospital stay being 12 +/- 3 days. In the group
      receiving glutamine in the treatment, there was a prominent decrease in leukocyte
      levels compared to the other group, and hospitalization times were shorter but
      there was no statistically significant difference in mortality or survival rates.
      CONCLUSIONS: Glutamine may decrease the catabolism. It may also have a positive
      effect on treatment time and the consequences of therapy in critically ill
      patients.

PMID- 15983686
TI  - Risk factors for hepatocellular carcinoma in Southern Iran.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common cancers in
      the world. Its etiology and incidence differ according to geographic area. In the
      present study, we sought to identify risk factors for HCC among a group of
      patients with HCC in Southern Iran. METHODS: During a 5-year period we
      retrospectively studied the characteristics of 71 HCC patients at Ahwaz
      Jundishapur University Hospital, Iran from February 1999 to August 2004. Blood
      samples and questionnaire data obtained from 71 (45 male and 26 female) incident
      cases of HCC, were pathologically diagnosed. Sera were tested for hepatitis B
      surface antigen and antibodies to hepatitis B core antigen, anti-hepatitis C
      virus and serum ferritin, iron and alfa fetoprotein (AFP), by enzyme immunoassays
      and cuper study. RESULTS: In 46.5% (33/71) of patients there was a history of
      chronic liver disease, and in 30 (42%) patients liver cirrhosis was documented.
      Of the 71 patients, 37 (52.1%) had hepatitis B, 6 (8.5%) had hepatitis C, and 2
      (2.8%) had a history of excess alcohol intake. Of the 2 patients with a history
      of heavy alcohol intake, one had concomitant chronic viral hepatitis infection,
      and alcohol alone was the etiology of HCC in only one case (1.40%). No etiologic
      cause was identified in 23 cases (32.4%), there were 2 cases of diabetes
      mellitus. The value of AFP of >20 ng/ml was found in 29 cases (41%), varying from
      24 ng/ml to 364 ng/ml (average 74.6 ng/ml). CONCLUSIONS: In Southern Iran, the
      predominant etiology of HCC was hepatitis B, hepatitis C, but alcohol and
      metabolic diseases were only found in rare cases. Cryptogenic cases may be found
      in one fifth of patients hence, the contribution of virus infection, may have
      been underestimated in this area, which is based on serological testing only.

PMID- 15983687
TI  - The risk factors of fall and their correlation with balance, depression,
      cognitive impairment and mobility skills in elderly nursing home residents.
AB  - OBJECTIVES: The purpose of this study was to investigate risk factors of fall and
      to examine their correlations with balance, depression, cognitive impairment and
      mobility skills in elderly nursing home residents. METHODS: This study included
      30 elderly people living in Seyranbaglari Nursing Home in Ankara City Centre,
      Turkey and was carried out in 2004. Risk factors for fall were obtained through
      individual interviews and observation. Cognitive function was assessed by Mini
      Mental State Examination (MMSE). The Geriatric Depression Scale (GDS) was used
      for determining the depression status of the elderly. Balance of the subjects was
      evaluated by the Berg Balance Scale (BBS) and the Get Up and Go Test (GUGT). In
      addition, mobility skills were assessed by Rivermead Mobility Index (RMI). The
      correlation analysis was used for establishing the correlations of the total
      number of risk factors with the other parameters. In addition, the correlations
      among all parameters were evaluated. RESULTS: At the end of the study, it was
      found that the correlation among all parameters was significant (p<0.01, p<0.05).
      For example, there was a significant correlation of MMSE score with the total
      number of risk factor for falls, GDS, BBS, GUGT and RMI. The RMI score was also
      correlated with GDS, MMSE, BBS and GUGT scores. CONCLUSION: The result of the
      present study confirm that impairment of cognitive function, balance and mobility
      skills, and depression increases the risk of falling. In addition, all the
      parameters affect each other, too. There is a vicious circle among these
      parameters. If this vicious circle is not broken, an increasing risk of fall will
      be inevitable. That is why this information will be useful for patients therapy,
      and for development of fall prevention programs for elderly people.

PMID- 15983688
TI  - Ruptured ovarian cysts and bilateral ectopic pregnancy complicating a case of
      severe ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS), ruptured ovarian cysts and bilateral
      ectopic pregnancies are all well-recognized entities occurring in association
      with infertility treatment. We are reporting a case of severe OHSS which was
      complicated initially by ruptured ovarian cysts and later by bilateral ectopic
      pregnancy. Diagnosis of tubal pregnancy was obscured by stimulated ovaries, which
      prevented accurate ultrasound definition. The role of transvaginal ultrasound,
      serial beta human chorionic gonadotropin and the place of paracentesis in
      diagnosing these cases are discussed.

PMID- 15983689
TI  - Paraplegia in a puerperal woman due to spinal metastasis from papillary carcinoma
      of the thyroid gland.
AB  - We present an unusual case of paraplegia which occurred on the second postnatal
      day. Investigations revealed a spinal mass at D-7 level. Histopathology of the
      tumor showed it to be a spinal metastasis from a solitary thyroid malignant
      nodule. The patient had laminotomy and biopsy, followed later by total
      thyroidectomy. She also had radiotherapy and radio-iodine ablation. We discuss
      the therapeutic modalities of such a condition.

PMID- 15983690
TI  - Localized extramedullary relapse after autologous hematopoietic stem cell
      transplantation in multiple myeloma.
AB  - Extramedullary plasmacytomas are rare manifestation of plasma cell malignancies.
      After hematopoietic stem cell transplantation HSCT, presentation of localized
      plasmacytoma with extramedullary growth is very unusual. We report a case of a 56
      year-old woman with Dune-Salmon stage IIIA immunoglobulin A-kappa multiple
      myeloma, which presented 120 days after autologous HSCT with extramedullary
      plasmacytoma arising from a lymph node in supraclavicular region. The patient had
      no pretransplant-history related with extramedullary disease. There was no
      increase of plasma cells in bone marrow or monoclonal protein in urine or serum.
      Aspiration smears of lymph node revealed a population of plasmacytoid cells at
      various stages of maturation. The patient was successfully treated with local
      radiotherapy and has remained progression-free for more than 20 months.

PMID- 15983691
TI  - An unusual association between splenectomy and Kikuchi's disease.
AB  - Kikuchi's disease is a clinico-pathologic entity of unknown etiology
      characterized by subacute inflammatory process of lymph nodes. It affects mostly
      women around the age of 30 years. It is usually a self limiting illness
      characterized by pyrexia, neutropenia, and cervical lymphadenopathy. We report a
      case of Kikuchi's disease in a patient with past history of splenectomy. A 35
      year-old otherwise healthy female patient presented with 15 days history of
      fever, night sweats, and right cervical lymphadenopathy. She was on no medication
      and had no contact with animals or patients with tuberculosis. Her past history
      revealed splenectomy for thrombocytopenia 14 years before presentation. Lymphoma
      was suspected and she was referred for a cervical lymph node biopsy. The final
      histopathology diagnosis revealed subacute necrotizing lymphadenitis consistent
      with Kikuchi's disease. This is the first case of Kikuchi's disease presenting in
      a post splenectomy patient.

PMID- 15983692
TI  - Inflammatory fibroid polyp of the ileum causing intussusception.
AB  - Intussusception in adults is a rare cause for intestinal obstruction and is
      usually secondary to some lesion in the gastrointestinal tract GIT. We report a
      case of intestinal obstruction due to ileo-colic intussusception; an inflammatory
      fibroid polyp formed the leading edge of the intussusceptum, which is a rare
      polypoidal lesion of the GIT.

PMID- 15983693
TI  - Pediatric myoepithelioma of the palate.
AB  - Myoepithelioma is a rare benign tumor. There are controversial subtypes that lack
      myogenic differentiation. A 2003 literature search listed only 12 cases of
      myoepithelioma of the maxillofacial region. This paper describes one case of
      pediatric myoepithelioma as an addition to the previously documented cases, and a
      review of the literature.

PMID- 15983694
TI  - Disseminated Candida albicans infection in an immunocompetent host.
AB  - Candida albicans CA is an opportunistic fungus, which lives in close association
      with its human host. Immuno-competence is the barrier to its tendency to invade.
      Normal skin, commensal bacteria and neutrophils are the first hurdles and once
      broken down by indwelling catheters, antibiotics or ablative chemotherapies,
      dissemination can occur with grave consequences. We describe a young patient with
      apparent full immune competence, who suffered from disseminated CA infection, her
      presentation, diagnosis and therapy with amphotericin B deoxycholate, which lead
      to her complete recovery and return to a productive life.

PMID- 15983695
TI  - Serious clopidogrel associated renal hematoma in a type 2 diabetic patient with
      primary hyperparathyroidism after extracorporeal shock wave lithotripsy.
AB  - Renal hematoma after extracorporeal shock wave lithotripsy SWL is a rare
      complication. We report a case of a large renal hematoma following SWL that
      resulted in nephrectomy in a type 2 diabetic patient with primary
      hyperparathyroidism using clopidogrel due to coronary heart disease CHD. Although
      it was claimed that preoperative use of clopidogrel was not associated with
      increased bleeding, all patients who are scheduled for SWL should be interrogated
      in terms of using of platelet aggregation inhibitors such as clopidogrel, and
      these drugs should be interrupted appropriately before undergoing SWL.

PMID- 15983696
TI  - Tubo-ovarian abscess in a postmenopausal woman with underlying ovarian carcinoma.

PMID- 15983697
TI  - Effects of maternal bilateral adrenalectomy on skin development.

PMID- 15983698
TI  - Treatment of vitiligo with topical 15% lactic acid solution in combination with
      ultra violet-A.

PMID- 15983699
TI  - Diabetes in Oman.

PMID- 15983700
TI  - Viral gastroenteritis in Saudi children.

PMID- 15983701
TI  - Biochemical parameters and Helicobacter pylori seropositivity of patients with
      cerebral infarct.

PMID- 15983702
TI  - Open Bankart repair using suture anchors and capsular shift for recurrent
      anterior shoulder dislocation.

PMID- 15983703
TI  - Bronchial artery embolization in China.

PMID- 15983704
TI  - Histopathological audit of appendicectomy specimens.

PMID- 15983705
TI  - Relationship between physical activity level and health related quality of life
      among university students.

PMID- 15983706
TI  - Assessment and care of children with low vision disability in Oman. Situation
      analysis.

PMID- 15983707
TI  - Consumer satisfaction with primary health care services in Hail City, Saudi
      Arabia.

PMID- 15983708
TI  - Bednar tumor.

PMID- 15983709
TI  - Cesarean section on request.

PMID- 15983710
TI  - Incisional hernia repair: abdominoplasty, tissue expansion, and methods of
      augmentation.
AB  - Incisional hernia repair without mesh mainly consists of tissue transfer to
      bridge or close the defect. Bridging includes rotational or free musculocutaneous
      flaps, rendering acceptable short-term results but a rather disappointing long
      term outcome. Abdominal wall closure where there has been significant loss of
      domain, with intraperitoneal organs residing permanently outside the abdominal
      cavity, can only be achieved using the patients' own tissue if preoperative
      expansion of the abdominal cavity is performed using artificial expanders or
      pneumoperitoneum. From a scientific point of view, however, evidence supporting
      any treatment option is weak because prospective randomized controlled trials are
      virtually impossible to conduct owing to the inhomogeneity of the patient
      population being considered. Treatment of this condition by the above-mentioned
      means should therefore be proposed on an individual basis utilizing one or more
      of the many possible techniques described.

PMID- 15983711
TI  - Incisional hernia repair: laparoscopic techniques.
AB  - Repair of incisional hernias using the laparoscopic technique has continued to
      evolve since its inception in 1991. An analysis of the current literature has
      revealed that hernias as large as 1600 cm2 have been successfully repaired with
      this method. The average size appears to be about 105 cm2. Several choices of a
      biomaterial are available today, differing in the type of synthetic product or
      products that are used to manufacture them. Others incorporate an absorbable
      component. The goal of all of them is to prevent adhesion formation. The fixation
      devices that can be used are also varied. The results of laparoscopic incisional
      hernia repair are described. The conversion rate of these procedures is an
      impressive 2.4% with an enterotomy rate of 1.8%. These results affirm the low
      risk of this operation. The recurrence rate of 4.2% confirms the permanence of
      the repair. This procedure may become the standard of care in the near future.

PMID- 15983712
TI  - Incisional hernia: open techniques.
AB  - Even with the routine use of mesh, repairing an incisional hernia is a challenge.
      Increasing evidence of impaired wound healing in these patients supports routine
      use of an open prefascial, retromuscular mesh repair. Basic pathophysiologic
      principles dictate that for a successful long-term outcome and prevention of
      recurrence a wide overlap underneath healthy tissue is required. The extent of
      this overlap should be 5 cm in all directions: surrounding the wound closure,
      subxiphoidal underneath the ribs, below the arcuate line, and retropubic.

PMID- 15983713
TI  - Groin hernia repair by laparoscopic techniques: current status and controversies.
AB  - Laparoscopic hernia repair remains controversial, and its position in current
      hernia surgery remains in flux. In this article we attempt to put the
      laparoscopic approach in perspective by describing the rationale for its
      development. We summarize studies comparing it with open repairs, including
      recent publications, meta-analyses, and systematic reviews; and we then contrast
      the data with recent findings of the United States Veterans Affairs Cooperative
      study 456. We discuss the current and future status of the laparoscopic approach
      to inguinal hernia repair and present an update of our own laparoscopic totally
      extraperitoneal technique without mesh fixation. From 1994 to 2004 we performed
      314 hernia repairs on 224 patients with no intraoperative complications, no
      conversions to an open procedure, and no mortality. Thirty (14%) minor
      postoperative complications occurred. There were three herniated lipomas
      (preperitoneal fat) but no true peritoneal reherniations. We evaluate critical
      points of laparoscopic hernia repair including extensive preperitoneal
      dissection, mesh configuration, size and fixation, cost reduction, and the
      learning curve.

PMID- 15983714
TI  - Groin hernia repair: open techniques.
AB  - Since the introduction of the Bassini method in 1887, more than 70 types of pure
      tissue repair have been reported in the surgical literature. An unacceptable
      recurrence rate and prolonged postoperative pain and recovery time after tissue
      repair along with our understanding of the metabolic origin of inguinal hernias
      led to the concept of tension-free hernioplasty with mesh. Currently, the main
      categories of inguinal hernia repair are the open repairs and the laparoscopic
      repairs. In the open category, repair of the hernia is achieved by pure tissue
      approximation or by tension-free mesh repair. The most commonly performed tissue
      repairs are those of Bassini, Shouldice, and to a lesser extent McVay. In the
      tension-free mesh repair category, the mesh is placed in front of the
      transversalis fascia, such as with the Lichtenstein tension-free hernioplasty, or
      behind the transversalis fascia in the preperitoneal space, such as during the
      Nyhus, Rives, Read, Stoppa, Wantz, and Kugel procedures. Numerous comparative
      randomized trials have clearly demonstrated the superiority of the tension-free
      mesh repair over the traditional tissue approximation method. Placing mesh behind
      the transversalis fascia, although a sound concept, requires extensive dissection
      in the highly complex preperitoneal space and can lead to injury of the pelvic
      structures, major hematoma formation, or both. In addition, according to the
      prospective randomized comparative study of mesh placement in front of versus
      behind the transversalis fascia, the latter offers no advantage over the former,
      and it is more difficult to perform, learn, and teach. More importantly,
      preperitoneal mesh implantation (via open and laparoscopic procedure) leads to
      obliteration of the spaces of Retzius and Bogros, making certain vascular and
      urologic procedures, in particular radical prostatectomy and lymph node
      dissection, extremely difficult if not impossible. In conclusion, according to
      level A evidence from randomized comparative studies, (1) mesh repair is superior
      to pure tissue approximation repairs, and (2) mesh implantation in front of the
      transversalis fascia is superior, safer, and easier than open or laparoscopic
      mesh implantation behind the transversalis fascia.

PMID- 15983715
TI  - Heart transplantation: the contributions of Christiaan Barnard and the University
      of Cape Town/Groote Schuur Hospital.
AB  - Christiaan (Chris) Neethling Barnard was born in South Africa and qualified in
      medicine at the University of Cape Town in 1946. Following surgical training in
      South Africa and the USA, Barnard established a successful open-heart surgery
      program at Groote Schuur Hospital and the University of Cape Town in 1958. In
      1967, he led the team that performed the world's first human-to-human heart
      transplant. Although the first heart transplant patient survived only 18 days,
      four of Groote Schuur hospital's first 10 patients survived for more than one
      year, two living for 13 and 23 years, respectively. This relative success amid
      many failures worldwide did much to generate guarded optimism that heart
      transplantation would eventually become a viable therapeutic option, Barnard then
      developed the operation of heterotopic heart transplantation (the socalled "piggy
      back" transplant), which had some advantages in the pre-cyclosporine era when
      immunosuppressive therapy was limited. His group was the first to successfully
      transport donor hearts using a hypothermic perfusion storage device in 1981.
      Several studies on the haemodynamic and metabolic sequelae of brain death were
      carried out in his Department's cardiovascular research laboratories at the
      University of Cape Town, and the concept of hormonal replacement therapy in organ
      donors was developed. An active heart transplant program still continues in the
      Chris Barnard Division of Cardiothoracic Surgery at Groote Schuur Hospital and
      the University of Cape Town, but the thrust of clinical activity within the
      Division and the research within its state-of-the-art cardiovascular research
      laboratories is now directed towards valvular and ischaemic heart diseases, which
      are common in the African population.

PMID- 15983717
TI  - Perspectives on surgery in the new South Africa.
AB  - Radical changes have occurred in the health care system since the democratization
      of South Africa in 1994, with the emphasis on improving previously neglected
      community-based primary health care. Because of the resultant financial
      constraints, funding of tertiary academic centers has been drastically cut which
      has compromised their proud record of service, teaching, and research excellence.
      Tertiary surgery has been particularly affected and now lags in the acquisition
      of new technologies which form an integral part of teaching and modern day
      practice. The acute shortage of full-time surgeons in regional public hospitals
      has prompted the government to fill vacancies with surgeons from foreign
      countries. In stark contrast, an abundance of surgeons in the relatively small
      private sector enjoy the benefits of the very best of First World medicine. The
      ultimate goal is a seamless progression of effective health care at all levels.
      It behooves the main role players to ensure that the high standard of training of
      South African doctors, which has international recognition, is maintained during
      this transition period.

PMID- 15983718
TI  - Selective conservatism in trauma management: a South African contribution.
AB  - Trauma in South Africa has been termed the malignant epidemic. This heritage was
      the result of a violent colonial legacy which spawned the apartheid system of
      injustice and the struggle against it The Apartheid regime created overcrowding,
      unemployment, social stagnation, and the disruption of normal family life. These
      were the catalysts for the incredible amount of criminal and interpersonal
      conflict in South Africa over the last 50 years. African townships such as Soweto
      in Johannesburg and Umlazi in Durban were crime-ridden ghettoes where the
      apartheid police were more interested in fueling the "black on black" violence
      rather than trying to curb it. Baragwanath (Chris Hani-Baragwanath) and King
      Edward the VIII Hospital in Durban were the "trauma care epicenters" on the
      fringes of these huge urban conurbations. Both were designated black hospitals
      and both were underfunded and dilapidated. Even the architecture was similar,
      with prefabricated, poorly ventilated structures serving as wards and clinics in
      both institutions. Trauma volumes consisted of between 10 and 20 laparotomies on
      weekend nights at the height of political unrest. This led to vast individual
      experience in several areas of trauma typified by Demetriades' experience with 70
      penetrating cardiac injuries. In this setting of limited resources and an
      overwhelming volume of trauma, selective conservatism as a surgical philosophy
      took root and has profoundly influenced the way the world manages trauma. We
      detail and illustrate the evolution of this approach and its continued
      application.

PMID- 15983723
TI  - Mikulicz's innovative achievements in the field of thyroid surgery.

PMID- 15983724
TI  - A simple alternative to line transects of nests for estimating orangutan
      densities.
AB  - We conducted a validation of the line transect technique to estimate densities of
      orangutan (Pongo pygmaeus) nests in a Bornean swamp forest, and compared these
      results with density estimates based on nest counts in plots and on female home
      ranges. First, we examined the accuracy of the line transect method. We found
      that the densities based on a pass in both directions of two experienced pairs of
      observers was 27% below a combined sample based on transect walks by eight pairs
      of observers, suggesting that regular line-transect densities may seriously
      underestimate true densities. Second, we compared these results with those
      obtained by nest counts in 0.2-ha plots. This method produced an estimated 15.24
      nests/ha, as compared to 10.0 and 10.9, respectively, by two experienced pairs of
      observers who walked a line transect in both directions. Third, we estimated
      orangutan densities based on female home range size and overlap and the
      proportion of females in the population, which produced a density of 4.25-4.5
      individuals/km(2) . Converting nest densities into orangutan densities, using
      locally estimated parameters for nest production rate and proportion of nest
      builders in the population, we found that density estimates based on the line
      transect results of the most experienced pairs on a double pass were 2.82 and
      3.08 orangutans/km(2), based on the combined line transect data are 4.04, and
      based on plot counts are 4.30. In this swamp forest, plot counts therefore give
      more accurate estimates than do line transects. We recommend that this new method
      be evaluated in other forest types as well.

PMID- 15983725
TI  - NF-kappaB is required for survival of immature auditory hair cells in vitro.
AB  - Damage to auditory hair cells in the inner ear as a consequence of aging,
      disease, acoustic trauma, or exposure to ototoxins underlies most cases of
      hearing impairment. Because the mammalian ear cannot replace damaged hair cells,
      loss of hearing is irreversible and progressive throughout life. One of the
      current goals of inner ear biology is to develop therapeutic strategies to
      prevent hair cell degeneration. Although important progress has been made in
      discovering factors that mediate hair cell death, very little is known about the
      molecular pathway(s) that signal survival. Here we considered the role of NF
      kappaB, a ubiquitous transcription factor that plays a major role in the
      regulation of many apoptosis- and stress-related genes, in mediating hair cell
      survival. NF-kappaB was detected in a constitutively active form in the organ of
      Corti of 5-day-old rats. Selective inhibition of NF-kappaB through use of a cell
      permeable inhibitory peptide in vitro caused massive degeneration of hair cells
      within 24 h of inhibitor application. Hair cell death occurred through an
      apoptotic pathway through activation of caspase-3 and may involve transcriptional
      down-regulation of the gadd45beta gene, an anti-apoptotic NF-kappaB target. In
      view of our results, it seems likely that NF-kappaB may participate in normal
      hair cell function.

PMID- 15983726
TI  - Ameliorative effects of exposing DBA/2J mice to an augmented acoustic environment
      on histological changes in the cochlea and anteroventral cochlear nucleus.
AB  - DBA/2J (D2) mice, which exhibit very early progressive sensorineural hearing
      loss, were treated nightly with an augmented acoustic environment (AAE) initiated
      before the onset of hearing, and consisting of repetitive bursts of a 70-dB sound
      pressure level (SPL), 4-25 kHz noise band. At 55 days of age, AAE-treated mice
      exhibited less elevation of auditory brainstem response thresholds, fewer missing
      hair cells, and greatly reduced loss of anteroventral cochlear nucleus (AVCN)
      volume and neuron number compared to untreated control mice. It was hypothesized
      that the central neuroprotective effect was associated with increased afferent
      input to AVCN neurons evoked by the AAE as well as a healthier cochlea.

PMID- 15983727
TI  - Thickness distribution of fresh eardrums of cat obtained with confocal
      microscopy.
AB  - The aim of this study was to measure the spatial thickness distribution of the
      cat tympanic membrane (TM), a very thin, virtually transparent and delicate
      biological membrane. Axial fluorescence images taken perpendicular through
      isolated TM were recorded for five different cats using confocal laser scanning
      microscopy. Thickness was measured on the cross-section of the membranes in the
      axial images. A correction for focal shift due to refractive-index mismatch was
      applied. Similar thickness distributions were obtained in all measured samples (n
      = 9). The pars tensa had a rather constant thickness in the central region
      between the annulus and manubrium. The thickness increased steeply toward the
      peripheral rim. Thickness was smallest in the inferior region, with values
      ranging between 5.5 and 9 microm in the central part and up to 50 microm near the
      annulus. More superiorly, thickness was slightly higher, up to 20 microm, between
      the annulus and manubrium. The anterior part was thicker than the posterior side.
      These findings are strongly different from a current value in the literature. Our
      data allow a more precise representation of the eardrum in mathematical models,
      which are a prerequisite for a better understanding of middle-ear mechanics. The
      optical sectioning technique of the confocal microscope did not result in any
      preparation artifacts and was therefore also used to quantify shrinkage due to
      preparation of histological sections of TMs.

PMID- 15983728
TI  - Structural determinants of hip fracture in elderly women: re-analysis of the data
      from the EPIDOS study.
AB  - Hip fracture is the most disastrous osteoporotic fracture, characterized by high
      mortality, morbidity and institutionalization for the patient and by high
      economic costs for the health care system. The morphology of the upper part of
      the femur can influence the risk of hip fracture, e.g., a longer femoral neck is
      associated with a higher risk of cervical fractures, but not trochanteric ones.
      In this study, we evaluated the prediction of hip fracture risk by morphological
      parameters estimated from DXA measurements, and we compared their predictive
      value for cervical and trochanteric fractures in elderly women by reanalyzing
      previously published data (Duboeuf et al. J Bone Miner Res 1997 12 1895). This
      nested case-control study was performed in 232 elderly community-dwelling women
      from the EPIDOS cohort, including 65 women who sustained a hip fracture. After
      adjustment for confounding variables, women who sustained a cervical fracture had
      lower areal bone mineral density (aBMD), lower cortical thickness and a higher
      average buckling ratio (P<0.005 for all) as well as longer femoral neck (P<0.01)
      than controls. Women who sustained a trochanteric fracture had lower aBMD, lower
      cortical thickness and higher buckling ratio than controls (P<0.0001) and than
      women who sustained a cervical fracture (P<0.05). Their bending resistance (cross
      sectional moment of inertia-CSMI, section modulus) was significantly lower in
      comparison with controls (P<0.05-0.001). A decrease in aBMD, cortical thickness,
      CSMI and section modulus as well as an increase in buckling ratio were predictive
      of all hip fractures (OR -1.42-2.46 per 1 SD, P<0.05-0.0001), but the ORs for all
      structural parameters were markedly higher for trochanteric than for cervical
      fractures. CSMI and section modulus were predictive of trochanteric, but not
      cervical fractures. However, aBMD was strongly correlated with the CSA, cortical
      thickness and buckling ratio (r2>0.74), which suggests that they convey the same
      information. CSMI and section modulus correlated with aBMD more weakly, but their
      OR lost statistical significance after adjustment for aBMD. In conclusion, low
      femoral neck aBMD, CSA and cortical thickness as well as a high buckling ratio
      are associated with the higher risk of hip fracture, especially trochanteric
      ones. These indices are highly correlated with aBMD and convey the same message.
      The calculated CSMI and section modulus predict trochanteric fractures, but not
      cervical fractures, and their statistical significance is lost after adjustment
      for aBMD, indicating that they reflect mainly aBMD, not mechanical properties.
      Thus, the independent contribution of the external diameter of the femoral neck
      to the risk of hip fracture cannot be reliably estimated by this technique.

PMID- 15983729
TI  - Guidelines for the management of osteoporosis: the present and the future.
AB  - Evidence-based guidelines are increasingly used in the management of osteoporosis
      and have the potential to produce uniformly high standards of clinical care
      across different sectors of the health service. National guidelines for the
      prevention and treatment of osteoporosis are now available in a number of
      countries and, although sharing similarities, also differ in some respects. This
      review considers the challenges involved in the development and implementation of
      guidelines and proposes a paradigm for the unification of guidelines in the
      future.

PMID- 15983730
TI  - Hepatitis C-associated osteosclerosis (HCAO): report of a new case with
      involvement of the OPG/RANKL system.
AB  - We report a new case of hepatitis C-associated osteosclerosis (HCAO). The
      clinical presentation of the patient was an acquired deep severe bone pain with
      increased serum bone alkaline phosphatase activity (up to 12 times the upper
      limit of normal), and generalized bone sclerosis, temporally related to the
      hepatitis C-virus (HCV) infection. We documented in this patient an increase of
      circulating osteoprotegerin (OPG), and a concentration of circulating receptor
      activator for nuclear factor-kB ligand (RANKL) below the lower limit of the
      reference range. The observed abnormalities of the OPG/RANKL system may
      contribute to the maintenance of the positive balance of bone remodeling that
      characterizes patients with HCAO.

PMID- 15983731
TI  - Colpocleisis: a review.
AB  - OBJECTIVE: To summarize published data about colpocleisis and to highlight areas
      about which data are lacking. DATA SOURCES: We conducted a literature search on
      Medline using Ovid and PubMed, from 1966 to January 2004, using search terms
      "colpocleisis", "colpectomy", "vaginectomy", "pelvic organ prolapse (POP) and
      surgery", and "vaginal vault prolapse and surgery" and included articles with
      English-language abstracts. We examined reference lists of published articles to
      identify other articles not found on the electronic search. METHODS OF STUDY
      SELECTION: We examined all studies identified in our search that provided any
      outcome data on colpocleisis. Because of the heterogeneity of outcome measures
      and follow-up intervals in case series, we did not apply meta-analytic techniques
      to the data. RESULTS: Colpocleisis for POP is apparently successful in nearly
      100% of patients in recent series. The rate of reoperation for stress
      incontinence or POP after colpocleisis is unknown. Concomitant elective
      hysterectomy is associated with increased blood loss and length of hospital stay,
      without known improvement in outcomes. Few studies systematically assess pelvic
      symptoms. The role of preoperative urodynamic testing to direct optimal
      management of urinary incontinence and retention remains to be established in
      this setting. CONCLUSIONS: Colpocleisis is an effective procedure for treatment
      of advanced POP in patients who no longer desire preservation of coital function.
      Complications are relatively common in this group of elderly patients.
      Prospective trials are needed to understand the impact of colpocleisis on
      functional outcomes and patient satisfaction.

PMID- 15983732
TI  - Inhibition by 2,4-toluene diisocyanate of the calcium signaling of neuronal
      nicotinic acetylcholine receptors in human neuroblastoma SH-SY5Y cells.
AB  - Toluene diisocyanate (TDI) is widely used as a chemical intermediate in the
      production of polyurethane products such as foams, coatings, and elastomers. In
      exposed workers, chronic inhalation of TDI has resulted in significant decreases
      in lung function. TDI-induced asthma is related to its disturbance of
      acetylcholine in most affected workers but the actions of TDI on nicotinic
      acetylcholine receptors (nAChR) are unclear. In order to understand the role of
      TDI acting on nAChR, we used human neuroblastoma SH-SY5Y cells to investigate the
      effects of TDI on cytosolic free calcium concentration ([Ca2+]c) changes under
      the stimulation of nAChR. The results showed that TDI was capable of inhibiting
      the [Ca2+]c rise induced by nicotinic ligands, epibatidine, DMPP and nicotine.
      The inhibition was remained, even increased after chronic treatment of TDI. Our
      study of TDI acting on human nAChR suggests a possibility that the human nerve
      system plays some role in the toxicity of TDI in the pulmonary system.

PMID- 15983733
TI  - The contribution of galactomannan detection in the diagnosis of invasive
      aspergillosis in bone marrow transplant recipients.
AB  - Until recently, accurate microbiological diagnosis of invasive aspergillosis (IA)
      was seldom established in HSCT recipients. Blood samples are rarely positive for
      Aspergillus species, the reliability of the cultures depends of the specimen (if
      taken from a normally sterile site or not) and biopsy samples require invasive
      procedures, rarely recommended in patients with severe thrombocytopenia.
      Implementing the international consensus defining the microbiological criteria
      for the diagnosis of Aspergillus infection, we retrospectively evaluated the role
      of serum galactomannan (GM) detection by EIA to diagnose IA among HSCT patients
      with proven invasive fungal infection (IFI) and the impact of serum storage in GM
      concentrations. The EIA assay allowed categorizing as "probable" 5 of the 10
      cases of "possible" aspergillosis (50%). Considering a lower cut-off level for
      the reaction (1.0), 80% of the cases could be categorized as "probable"
      aspergillosis. Positive or undetermined results were detected one to 4 months
      before the diagnosis of IA in eight of the 11 patients (72.7%) with proven IFI.
      Retesting the stored samples after a second storage for four years, we could
      observe lower reactivity in 20% of the samples. The detection of galactomannan by
      the EIA test represents a major advance in the diagnosis of IA in HSCT recipients
      at high risk of IA. A better understanding of the kinetics of the GM in different
      clinical situations is necessary to maximize the benefit of the test in
      Aspergillus surveillance.

PMID- 15983734
TI  - The mycological and molecular study of Hortaea werneckii isolated from blood and
      splenic abscess.
AB  - Hortaea werneckii is an environmental dematiaceous fungus found in the halophilic
      environment. It causes tinea nigra. We report the isolation of H. werneckii from
      blood and splenic abscess of two patients with acute myelomonocytic leukaemia. H.
      werneckii grew at room temperature but not at 37 degrees C, it was identified by
      biochemical tests, growth characteristics and the presence of conspicuous
      collarette intercalary on dividing yeast cells. The use of specific
      oligonucleotide primer Hor-F (5'-TGGACACCTTCA TAACTCTTG-3') and Hor-R (5'
      TCACAACGCTTAGAGACGG-3') confirmed the two isolates were H. werneckii. The
      sequence for 281 nucleotide of HW299 and HW403 were 99% identical but differed
      only in one nucleotide. In vitro anti-fungal susceptibility testing showed that
      the isolates were resistant to amphotericin B and flucytosine.

PMID- 15983735
TI  - Vulvovaginal candidiasis is associated with the production of germ tubes by
      Candida albicans.
AB  - Twenty Candida albicans strains isolated from women attended at the Teaching and
      Research in the Laboratory of Teaching and Research in Clinical Analysis of the
      State University of Maringa, Parana, Brazil, have been analyzed. Yeasts were
      identified by classical methods and patients subdivided into asymptomatic,
      vulvovaginal candidiasis(VVC) and recurrent vulvovaginal candidiasis (RVVC)
      groups. Yeasts were incubated in RPMI + fetal calf serum to analyze germ tubes
      every two hours, up to 10 h. In vitro sensitivity to fluconazole, itraconazole,
      ketoconazole, amphotericin B and nystatin was analyzed according to NCCLS-M27-A
      microdilution assay. Yeast isolated from symptomatic women produced significantly
      more germ tubes than asymptomatic women (P < 0.05). However, no significant
      difference between yeasts from VVC and RVVC occurred (P > 0.05). Variation
      between MIC50 and MIC90 of tested antifungal agents was slight among isolated
      yeasts, while no resistant yeasts were detected. Nevertheless, VVC yeasts were
      more DDS (reduced dose-dependent susceptibility) for nystatin and RVVC were more
      DDS for ketoconazole. Results suggest that colonization by yeast in the vagina
      and lack of symptoms may be partially explained by the yeast's sparse capacity to
      form germ tubes, On the other hand, RVVC was not associated with antimicrobial
      resistance. DDS high frequency for nystatin and ketoconazole indicates that
      identification, and susceptibility of antifungals tests are important to
      management of VVC.

PMID- 15983736
TI  - The isolation, characterization and antifungal susceptibilities of Cryptococcus
      neoformans from bird excreta in Klang Valley, Malaysia.
AB  - The occurrence of Cryptococcus neoformans in bird excreta in Klang valley,
      Malaysia was determined in this study. Of 544 samples of bird excreta collected
      from a local zoo, pet shops and public areas, 20 strains of C. neoformans were
      isolated. All C. neoformans strains were serotype A and thus identified as C.
      neoformans variety grubii. All did not produce color changes on canavanine
      glycine-bromothymol blue agar. All were of alpha-mating types, as determined by a
      pheromone-specific PCR assay. The antifungal susceptibility testing using agar
      diffusion method Neo-sensitabs showed that all were susceptible to amphotericin
      B, fluconazole and itraconazole.

PMID- 15983737
TI  - Fecal fungal flora of pediatric healthy volunteers and immunosuppressed patients.
AB  - Most hematogenous candidiasis originates from endogeneous host flora. Fungal
      flora of gastrointestinal system are important source of infection especially in
      immunosupressed patients. The purpose of this study was to investigate the fecal
      fungal flora of pediatric patients with hematologic malignancy or disorders and
      to compare the results with healthy volunteers. For this purpose, fungal
      etiological agents were investigated retrospectively in stool samples of 80
      patients followed in Bone marrow transplantation and Hematology-Oncology units.
      The diagnosis of patients were as follows: 26 acute myelogeneous leukemia, 19
      acute lymphocytic leukemia, 5 lymphoma, 3 chronic myelogeneous leukemia, 2 solid
      tumor, 4 neuroblastoma and 21 hematologic disorders. In patients, totally 102
      fungal growth was detected and 42 (41.2%) C. albicans and 51 (50%) non-albicans
      Candida species and 9 (8.8%) yeast other than Candida and mould was isolated. The
      results were compared prospectively with growth in stool samples of 61 healthy
      children. C. albicans was detected in 16 (43.2%) and non-albicans Candida species
      in 15 (40.5%) and yeasts other than Candida and mould in 6 (16.2%) of 37 fungal
      growth in controls. Non-albicans Candida species growth was found significantly
      higher and C. glabrata was more prevelant in patients than in controls (p <
      0.001).

PMID- 15983738
TI  - Successful treatment of antifungal- and cryotherapy-resistant subcutaneous
      hyalohyphomycosis in an immunocompetent case with topical 5% imiquimod cream.
AB  - Hyalohyphomycosis is an unusual opportunistic mycotic infection where the tissue
      morphology of the causative organism is mycelial. Etiological agents, which are
      not responsible for the otherwise-named infections like aspergillosis, are the
      species of non-dematiaceous hyaline hyphomycetes including Penicillium,
      Paecilomyces, Acremonium (formerly known Cephalosporium), Beauveria, Fusarium,
      and Scopulariopsis. Several cases of Acremonium infection have been described in
      immunocompromised patients; however it can cause invasive disease in an
      immunocompetent person very rarely. Optimum therapy of Acremonium infection is
      unclear because of the limited number of reported cases and conflicting results
      of therapies. Imiquimod, an imidazoquinoline with potent antiviral, antitumor and
      immunoregulatory properties, is currently approved for the topical treatment of
      external anogenital warts and actinic keratosis. Imiquimod has also been found to
      be effective for other virus-associated dermatologic lesions, including common
      and flat warts, molluscum contagiosum, and herpes simplex virus type-2 as well as
      for some cases of cutaneous leishmaniasis. We report herein, for the first time,
      a case of unusually recalcitrant hyalohyphomycosis of the face due to Acremonium
      strictum successfully treated with topical 5% imiquimod in an immunocompetent
      patient, who had failed to respond to various antifungals, including
      itraconazole, and cryotherapy.

PMID- 15983739
TI  - Effects of combining the fungi Beauveria bassiana and Metarhizium anisopliae on
      the mortality of the tick Amblyomma variegatum (ixodidae) in relation to seasonal
      changes.
AB  - The effect of formulation, fungal concentration, type and seasonal changes on the
      mortality of the tick Amblyomma variegatum was investigated. A previous study
      demonstrated high pathogenicity of strains of the fungi Beauveria bassiana and
      Metarhizium anisopliae against the ticks Rhipicephalus appendiculatus and
      Amblyomma variegatum (Kaaya et al. J Invertebr Pathol 1996; 67: 15-20). The
      present study was undertaken to explore possible additive or synergistic effects
      of the two fungi on A. variegatum. The effects of oil and water formulations at
      different concentrations of each fungus and combination of the two on the
      mortality of A. variegatum in the laboratory and in the field during the wet and
      dry seasons were determined and compared. The oil formulation performed better in
      all assays, with highest tick mortality of 92% occurring during the wet season at
      conidia concentration of 1 x 10(10) conidia/ml of the mixed fungi compared to 49%
      for the water formulation at similar conidia concentration. However, at the same
      conidial concentration during the dry season, mortalities in the field were
      relatively low with the mixture of the fungi recording 24% and 17% tick mortality
      for the oil and water formulation respectively. The effect of infecting the ticks
      with a cocktail of the two fungi was inconclusive under more controlled
      conditions in the laboratory but field results under both wet and dry seasons
      indicated significant differences between the separate and mixed fungi
      infections. The results demonstrate a potential of cocktail formulations in the
      control of ticks and possibly of other arthropod pests.

PMID- 15983740
TI  - Improvement on genetic transformation in the nematode-trapping fungus
      Arthrobotrys oligospora and its quantification on dung samples.
AB  - An improved DNA-mediated transformation system for nematode-trapping fungus
      Arthrobotrys oligospora based on hygromycin B resistance was developed. The
      transformation frequency varied between 34 and 175 transformants per microg
      linearized DNA and 93% of the transformants were stable for drug resistance when
      tested 100 randomly selected transformants. More than 2000 transformants were
      obtained by transformation of the fungus with pBChygro in the presence of HindIII
      and among them, one, YMF1.00110, which lost its ability of forming predacious
      structure, was isolated. Southern analysis showed that the plasmid DNA had
      integrated into the genome of all tested transformants (including YMF 1.00110)
      except one. The transformant tagged with hph gene could be re-isolated and
      quantified from dung samples based on the resistance of hygromycin B. All the
      results suggested that the method of restriction enzyme mediated integration
      (REMI) should facilitate not only the insertional mutagenesis for tagging and
      analysis genes of interest but also the ecological investigation of tagged fungi
      in a given environment.

PMID- 15983741
TI  - Modeling effects of environment, insect damage, and Bt genotypes on fumonisin
      accumulation in maize in Argentina and the Philippines.
AB  - Fumonisins are common contaminants of maize (Zea mays L.) grain products,
      especially in countries where maize is a major constituent of the diet and are
      harmful to human and animal health. There is a need to better define
      environmental conditions that favor fumonisin accumulation in the grain of maize.
      The impacts of biotic and abiotic factors, and hybrids containing the Cry1Ab
      protein from Bacillus thuringiensis (Bt), were associated with fumonisin
      accumulation in the grain of maize across contrasting environments in Argentina
      and the Philippines between 2000 and 2002. Average fumonisin concentrations in
      grain samples varied from 0.5 to 12 microg g(-1) across field locations in
      Argentina, and from 0.3 to 1.8 microg g(-1) across locations in the Philippines.
      The ratio of fumonisin B1 to fumonisin B2 was <3.0 in four of nine locations in
      Argentina, which proved to be due to a higher prevalence of Fusarium proliferatum
      in those locations. Most of the variability of total fumonisins among maize grain
      samples was explained by location or weather (47%), followed by insect damage
      severity in mature ears (17%), hybrid (14%), and with the use of Bt hybrids
      (11%). In Argentina, where conditions were more favorable for accumulation of
      fumonisin in the years considered, fumonisin concentrations were lower in Bt
      hybrids compared to their genetic isolines by an average of 40%. A model was
      developed to predict fumonisin concentration using insect damage to ears and
      weather variables as predictors in the model. Four periods of weather around
      silking were identified as critical for fumonisin concentrations at harvest. The
      model accounted for 82% of the variability of total fumonisin across all
      locations in 2 years of the study.

PMID- 15983742
TI  - Comparative pathologic changes in broiler chicks on feed amended with Fusarium
      proliferatum culture material or purified fumonisin B1 and moniliformin.
AB  - Feed amended with autoclaved culture material (CM) of Fusarium proliferatum
      containing fumonisin B1 (FB1) (61-546 ppm), fumonisin B2 (FB2) (14-98 ppm) and
      moniliformin (66-367 ppm) was given to 228 male chicks in three separate feeding
      trials. In a fourth feeding trial, purified FB1 (125 and 274 ppm) and
      moniliformin (27 and 154 ppm) were given separately and in combination (137 and
      77 ppm, respectively). Chicks that died during the trial periods, survivors and
      controls were subjected to postmortem examination. Specimens (liver, kidney,
      pancreas, lung, brain, intestine, testis, bursa of Fabricius, heart and skeletal
      muscle) were examined grossly and preserved for subsequent histopathologic and
      ultrastructural examination. Prominent gross lesions in affected birds fed diets
      amended with CM or purified FB1 and moniliformin included ascites,
      hydropericardium, hepatopathy, nephropathy, cardiomyopathy, pneumonitis, gizzard
      ulceration, and enlarged bursa of Fabricius filled with caseous material. The
      various concentrations of FB1 and moniliformin in the amended rations produced
      well-defined dose-response lesions in all groups in all four trials.
      Histopathologic changes included hemorrhage, leucocytic infiltration, fatty
      change or infiltration, individual cell necrosis and fibrosis in liver, kidneys,
      lungs, heart, intestines, gizzard, bursa of Fabricius and pancreas. Edema and
      hemorrhage were prominent in brains of treated birds. Ultrastructural changes
      included cytoplasmic and nuclear enlargement of cells in affected liver, lungs,
      kidneys, heart and pancreas. There were thickened membranes of the smooth
      endoplasmic reticulum, dilation of the rough endoplasmic reticulum with loss of
      ribosomes and vacuolated or deformed mitochondria.

PMID- 15983743
TI  - Morphological alterations in toxigenic Aspergillus parasiticus exposed to neem
      (Azadirachta indica) leaf and seed aqueous extracts.
AB  - The mode of action of the extracts prepared from neem plant i.e., Azadirachta
      indica on aflatoxin formation in toxigenic Aspergillus species is not well
      understood. Aflatoxin production by A. parasiticus was suppressed depending on
      the concentration of the plant aqueous extract (0, 1.56, 3.12, 6.25, 12.5, and
      50% v/v) added to the culture media at the time of spore inoculation. Aflatoxin
      production in fungal mycelia grown for 96 h in culture media containing 50% neem
      leaf and seed extracts was inhibited by approximately 90 and approximately 65%
      respectively. Under similar conditions, culture media amended with 1.56% of leaf
      or seed extract caused approximately 23 and approximately 7% inhibition
      respectively. Mycelial samples exposed to selected concentrations of the plant
      extract (1.56 or 50% v/v) collected and processed for morphological studies. Semi
      thin longitudinal and cross sections prepared from control (untreated) and
      treated mycelia (1.56% v/v) revealed that alterations are limited to the
      vacuolation of the mycelial cytoplasm. Nevertheless, exposure to high
      concentration i.e., 50% v/v of the extract resulted in vacuolation of the
      mycelial cytoplasm and vesicle deformation causing attenuation of cell wall at
      variable intervals. Herniation of the cytoplasmic contents that was protruding
      from the mycelium was associated with deformation of the mycelium. Some mycelia
      showed a cleft between the cell wall and cytoplasm. Association of aflatoxin
      production with morphological changes suggest that probably integrity of the cell
      barriers particularly cell wall is critical in regulation of aflatoxin production
      and excretion.

PMID- 15983745
TI  - Divergent regulation of aflatoxin production at acidic pH by two Aspergillus
      strains.
AB  - Production of aflatoxins (AF) by Aspergillus flavus and A. parasiticus is known
      to occur only at acidic pH. Although typical A. flavus isolates produced more AF
      as the external pH became increasingly acidic, an atypical strain from West
      Africa produced less. The lower AF production was not well correlated with
      decreases in expression of the aflatoxin pathway regulatory gene, aflR, or of two
      other biosynthesis genes.

PMID- 15983744
TI  - Isolation and metabolite production by Penicillium roqueforti, P. paneum and P.
      crustosum isolated in Canada.
AB  - Penicillium roqueforti, P. crustosum and P. paneum grow on ensiled grain and
      recycled feed unless properly treated. The former two species occur also on cut
      lumber in Canada. These are known to produce a number of secondary metabolites
      including roquefortine. In cooler dairy production areas, including Scandinavia
      and North America, cattle toxicosis has been associated with silage contaminated
      by these fungi. We collected strains associated with cow or cattle toxicoses. The
      principal metabolites were determined making use of a new extraction method and
      analysis combining HPLC, LC/MS/MS, and LC/NMR. Penicillium roqueforti and P.
      crustosum required amino acid nitrogen for metabolite formation and their toxins
      were formed under conditions of low oxygen (20-30% saturation). Production of
      roquefortine C occurred on depletion of the available nitrogen and penitrem A on
      depletion of carbon source. Yield was reduced by excess carbon. Medium osmotic
      tension (aw) affected metabolite production by the two species differently.
      Penicillium paneum was associated with ill-thrift of dairy cows and P. roqueforti
      was associated with more serious symptoms. Our data suggest a physiological basis
      for the common occurrence of roquefortine C in silage without serious
      consequences and the alternative, the presence of roquefortine C and toxicoses.
      The strain isolated from lumber was the best producer of the toxins studied. This
      is the first report of the toxigenic potential of P. roqueforti and P. paneum
      from Canada.

PMID- 15983746
TI  - Morphological characteristics of sclerotia formed from hyphae of Grifola
      umbellata under artificial conditions.
AB  - The morphological characteristics of sclerotia were induced in cultures of the
      fungus Grifola umbellata by introducing an unidentified companion fungus were
      studied by light microscope, scanning and transmission electron microscope (SEM
      and TEM). Light microscope and SEM investigations of developing sclerotia
      revealed that aerial mycelial hyphae diminished with age, and mature sclerotia
      had two tissue layers, the rind and medulla. The medulla was comprised of thin
      and thick-walled hyphae of varying diameter. The thick-walled cells always formed
      below the hyphal tips. Retraction of the cytoplasm was accompanied by the
      thickening of cell wall. There were crystalline initials in the newly formed
      sclerotium. Crystalline initials were always formed in the tip of medullary
      hyphae and were not of regular shape. A series of changes occurred in the cells
      in which the crystalline initials would be formed, such as enlargement of size,
      formation of one or several large vacuoles. Crystalline initials developed via
      amorphous materials in the cytoplasm deposited in the vacuoles. At last
      crystalline initials was released by degradation of the cell wall.

PMID- 15983747
TI  - Plasmid distribution in European Diaporthe helianthi isolates.
AB  - Diaporthe helianthi is the causal agent of sunflower stem canker, a serious
      pathogen of sunflower in Europe, which has been sporadically recorded in Italy. A
      collection of 26 Diaporthe helianthi isolates deriving from different geographic
      origins was analysed in order to determine the presence of extra-chromosomal
      genetic determinants and their molecular diversity. Extra-chromosomal bands in
      total genomic DNAs were identified in every French and the Yugoslavian isolate
      and in only one Italian isolate, while no Romanian and Argentinean isolates
      resulted to host any plasmids. When tested for their chemicophysical nature, they
      were recognised as linear plasmids sized about 2.3 Kb. A more detailed analysis
      was performed on a plasmid purified from a French isolate (plasmid F). Its
      intracellular localisation resulted as mitochondrial. Plasmid F was also
      exploited as a probe in Southern hybridisation experiments, in which it
      recognised only plasmids present in the genomes of French and Yugoslavian
      isolates (countries were the disease has a heavy incidence) indicating a strong
      correlation to geographic origin. An RFLP hybridisation analysis performed on
      genomic DNAs revealed a homogeneous restriction pattern in all French and
      Yugoslavian isolates, suggesting molecular homology among plasmids present in
      those isolates.

PMID- 15983748
TI  - Pythium vexans causing patch canker of rubber trees on Hainan Island, China.
AB  - This is the first report of patch canker disease of rubber trees (clone RRIM600)
      in China. It is characterized by discrete irregular patches of rotted, discolored
      bark and wood, accompanied by a decrease in latex flow. A total of seven isolates
      of Pythium vexans were obtained from the diseased bark of the trunks and roots of
      rubber trees. Inoculating these isolates into healthy, mature rubber trees
      resulted in symptoms similar to patch canker and the same fungal species was re
      isolated from the diseased tissues. This is also the first record of Py. vexans
      in Hainan.

PMID- 15983752
TI  - High shoot plasticity favours plant coexistence in herbaceous vegetation.
AB  - Several theoretical considerations imply that high shoot morphological plasticity
      could increase competition symmetry and favour plant coexistence. We tested
      whether mean plasticity across co-occurring species is a key trait for explaining
      ramet density and species richness in herbaceous vegetation. We used three data
      sets to test the hypotheses: (a) experimentally achieved estimates of plasticity
      to light availability for 35 herbaceous species; (b) richness, ramet density and
      canopy architecture data from 17 herbaceous communities; (c) species richness
      data from a 5-year permanent-plot study in a calcareous grassland. In herbaceous
      communities containing species with relatively higher shoot plasticity, ramet
      density was significantly higher. Consequently, relatively more species were
      growing per unit area-a greater proportion of the community species pool was
      represented on 1 m(2). In the permanent plot study species-richness was higher in
      those 40 x 40 cm quadrats where species with high shoot plasticity prevailed
      there was a positive regression of richness on the mean plasticity of species.
      This relationship was highly significant in five consecutive years. Our results
      suggest that shoot plasticity to light availability is evidently one of the key
      traits in processes that alter the density of co-existing plants and, therefore,
      species diversity in herbaceous communities.

PMID- 15983754
TI  - [Painless jaundice after holidays in Tanzania].
AB  - The side effects caused by malaria prophylaxis with mefloquine (Lariam) are well
      known. We describe the case of a 42-year-old female Caucasian patient suffering
      from painless jaundice and showing elevated liver, cholestasis and inflammation
      laboratory findings 7 days after returning from Tanzania. Acute cholecystitis was
      diagnosed by ultrasound. Treatment with parenteral nutrition and antibiotic
      therapy did not show any beneficial effect. Excluding the possibility of
      infectious diseases, the elevated laboratory and ultrasound findings were
      normalized after the discontinuation of the malaria prophylaxis.

PMID- 15983753
TI  - [Surgical therapy for hand infections Part 2].
AB  - Due to its function, anatomy, and exposition to multiple pathogens, the hand is
      highly susceptible to infection. Most of these infections are post-traumatic.
      Isolates of pathogens from infected hands contain mainly Staphylococcus aureus
      and ss-haemolytic group A streptococci. But differential diagnosis also includes
      pyoderma gangrenosum, tumors of the hand, rheumatoid arthritis, and articular
      gout, as they may mimic hand infections. Infections of the hand can lead to
      massive tissue damage that needs to be reconstructed. The selection of methods
      depends on the localization and size of defects and includes primary closure,
      split- and full-thickness skin grafts, and more complex operations such as local,
      regional, and distant flaps.

PMID- 15983755
TI  - [Pulmonary manifestations in rheumatic systemic diseases].
AB  - Collagen based vascular diseases with pulmonary involvement comprise rheumatoid
      arthritis, systemic lupus erythematosus, progressive systemic sclerosis,
      dermatomyositis and polymyositis, ankylosing spondylitis, Sjogren's syndrome, and
      mixed connective tissue diseases. The different characteristics of pulmonary
      involvement are described. In such circumstances, early recognition of lung
      involvement is of considerable significance and the relationship to the
      corresponding disease has to be made. Frequently unrecognised pulmonary
      involvement ends up as fibrosis with irreversible deficits in respiratory
      function.

PMID- 15983756
TI  - Molecular dissection of interspecific variation between Gossypium hirsutum and
      Gossypium barbadense (cotton) by a backcross-self approach: I. Fiber elongation.
AB  - The current study is the first installment of an effort to explore the secondary
      gene pool for the enhancement of Upland cotton (Gossypium hirsutum L.) germplasm.
      We developed advanced-generation backcross populations by first crossing G.
      hirsutum cv. Tamcot 2111 and G. barbadense cv. Pima S6, then independently
      backcrossing F(1) plants to the G. hirsutum parent for three cycles. Genome-wide
      mapping revealed introgressed alleles at an average of 7.3% of loci in each
      BC(3)F(1) plant, collectively representing G. barbadense introgression over about
      70% of the genome. Twenty-four BC(3)F(1) plants were selfed to generate 24
      BC(3)F(2) families of 22-172 plants per family (totaling 2,976 plants), which
      were field-tested for fiber elongation and genetically mapped. One-way analysis
      of variance detected 22 non-overlapping quantitative trail loci (QTLs)
      distributed over 15 different chromosomes. The percentage of variance explained
      by individual loci ranged from 8% to 28%. Although the G. barbadense parent has
      lower fiber elongation than the G. hirsutum parent, the G. barbadense allele
      contributed to increased fiber elongation at 64% of the QTLs. Two-way analysis of
      variance detected significant (P<0.001) among-family genotype effects and
      genotypexfamily interactions in two and eight regions, respectively, suggesting
      that the phenotypic effects of some introgressed chromosomal segments are
      dependent upon the presence/absence of other chromosomal segments.

PMID- 15983757
TI  - Molecular dissection of phenotypic variation between Gossypium hirsutum and
      Gossypium barbadense (cotton) by a backcross-self approach: III. Fiber length.
AB  - A backcross-self population from a cross between Gossypium hirsutum and G.
      barbadense was used to dissect the molecular basis of genetic variation governing
      15 parameters that reflect fiber length. Applying a detailed restriction fragment
      length polymorphism (RFLP) map to 3,662 BC(3)F(2) plants from 24 independently
      derived BC(3) families, we detected 28, nine, and eight quantitative trait loci
      (QTLs) for fiber length, length uniformity, and short fiber content,
      respectively. For eight, six, and two chromosomal regions containing quantitative
      trait loci (QTLs) for fiber length, length uniformity, and short fiber content
      (respectively), two-way analysis of variance showed a significant (P<0.001) among
      family genotypic effect. A total of 13, two, and four loci showed genotype x
      family interaction, illustrating some of the complexities that are likely to be
      faced in introgression of exotic germplasm into the gene pool of cultivated
      cotton. Co-location of many QTLs for fiber length, length uniformity, and short
      fiber content accounted for correlations among these traits, while the discovery
      of many QTLs unique to each trait suggests that maximum genetic gain will require
      breeding efforts that target each trait (or an index including all three). The
      availability of DNA markers linked to G. barbadense QTLs identified in this and
      other studies promise to assist breeders in transferring and maintaining valuable
      traits from exotic sources during cultivar development.

PMID- 15983758
TI  - QTLs mapping for fruit size and shape in chromosomes 2 and 4 in pepper and a
      comparison of the pepper QTL map with that of tomato.
AB  - Quantitative trait locus (QTL) mapping for fruit weight and shape in pepper
      (Capsicum spp.) was performed using C. chinense and C. frutescens introgression
      lines of chromosomes 2 and 4. In chromosome 2, a single major fruit-weight QTL,
      fw2.1, was detected in both populations that explained 62% of the trait
      variation. This QTL, as well as a fruit-shape QTL, fs2.1, which had a more minor
      effect, were localized to the tomato fruit-shape gene ovate. The cloned tomato
      fruit-weight QTL, fw2.2, did not play a major role in controlling fruit size
      variations in pepper. In chromosome 4, two fruit-weight QTLs, fw4.1 and fw4.2,
      were detected in the same genomic regions in both mapping populations. In
      addition, a single fruit-shape QTL was detected in each of the mapping
      populations that co-localized with one of the fruit-weight QTLs, suggesting
      pleiotropy or close linkage of the genes controlling size and shape. fw2.1 and
      fw4.2 represent major fruit-weight QTLs that are conserved in the three Capsicum
      species analyzed to date for fruit-size variations. Co-localization of the pepper
      QTLs with QTLs identified for similar traits in tomato suggests that the pepper
      and tomato QTLs are orthologous. Compared to fruit-shape QTLs, fruit-weight QTLs
      were more often conserved between pepper and tomato. This implies that different
      modes of selection were employed for these traits during domestication of the two
      Solanaceae species.

PMID- 15983759
TI  - Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a
      prospective cohort study.
AB  - OBJECTIVE: To assess renal dysfunction and outcome in patients treated
      exclusively with colistin vs. other antibiotics. DESIGN AND SETTING: Prospective
      cohort study in a mixed ICU in a university-affiliated hospital. PATIENTS: 185
      patients infected with Acinetobacter baumannii and Pseudomonas aeruginosa after
      an ICU stay longer than 48 h: 55 in the colistin group and 130 in the noncolistin
      group, similar in age, APACHE II, medical status, and SOFA score. MEASUREMENTS
      AND RESULTS: We recorded data on epidemiology and severity of illness, site of
      infection, renal function before and after treatment, clinical cure, and
      mortality. Clinical cure was defined as simultaneous normalization of central
      temperature (< or = 38 degrees), leukocyte count (< or = 10,000/mm3), and
      PaO2/FIO2 ratio (>187). Before treatment creatinine was 0.9+/-0.2 in the colistin
      group and 0.9+/-0.1 in the noncolistin group; after treatment the value was 1.0+/
      0.3 in both groups. The most frequent infection was ventilator-associated
      pneumonia: 53% vs. 66% in colistin and noncolistin groups, respectively,
      Acinetobacter was the cause in 65% and 60% and Pseudomonas in 35% and 53%. In the
      noncolistin group 81% of patients were treated with carbapenems. Inadequate
      empirical antimicrobial treatment was more frequent in the colistin group (100%
      vs. 8%), but there were no differences in the frequency of clinical cure on day 6
      of treatment (15% and 17%) or in mortality (29% and 24%). CONCLUSIONS: Colistin
      appears to be as safe and as effective as other antimicrobials for treatment of
      sepsis caused by Acinetobacter and Pseudomonas in critically ill patients.

PMID- 15983760
TI  - Candesartan improves survival following severe hypovolemia in pigs; a role for
      the angiotensin II type 2 receptor?
AB  - OBJECTIVE: To investigate the involvement of intestinal angiotensin II type 2
      receptors in the outcome of acute severe hypovolemia as well as systemic and
      regional mesenteric hemodynamics and intestinal mucosal functions in anesthetized
      pigs. DESIGN AND SETTING: Prospective, interventional animal study in a
      university research laboratory. SUBJECTS: 53 landrace pigs, 28-35 kg.
      INTERVENTIONS: 30+30% or 20+20% hemorrhage of estimated total blood volume
      followed by retransfusion performed in untreated controls, in animals treated
      with the angiotensin II type 1 receptor blocker candesartan or with a combination
      of candesartan and the angiotensin II type 2 receptor blocker PD123319.
      MEASUREMENTS AND RESULTS: Following 30+30% hemorrhage the candesartan-treated
      animals attained a significantly higher survival rate than controls and animals
      treated with PD123319 in combination with candesartan. Less pronounced hemorrhage
      (20+20%) resulted in no mortality and functional variables were assessed. A
      significantly higher output of jejunal intraluminal nitric oxide occurred during
      hypovolemia in the candesartan treated group than in controls and animals that
      received PD123319 in combination with candesartan. Jejunal transmucosal potential
      difference was significantly better preserved after retransfusion in candesartan
      treated animals than in controls. Expression of angiotensin II type 2 receptors
      in intestinal tissue was significantly higher in animals surviving the 30+30%
      hemorrhage than in nonsurvivors. CONCLUSIONS: Lethal circulatory failure is
      possibly influenced by use of angiotensin receptor ligands, and activation of
      intestinal angiotensin II type 2 receptors may play a significant role in
      improving the outcome of severe hypovolemia.

PMID- 15983761
TI  - BIBN4096BS and CGRP(8-37) antagonize the relaxant effects of alpha-CGRP more than
      those of beta-CGRP in human extracranial arteries.
AB  - We hypothesize that dilatation of extracranial arteries during migraine could be
      caused by CGRP. We compared the relaxant effects of alpha-calcitonin gene-related
      peptide (alpha-CGRP) and beta-calcitonin gene-related peptide (beta-CGRP) and the
      antagonism by BIBN4096BS and CGRP(8-37) on rings of human temporal and occipital
      arteries precontracted with KCl. beta-CGRP relaxed temporal (-logEC50M = 8.1) and
      occipital arteries (-logEC50M = 7.6) with 19-fold and 29-fold lower potencies
      respectively than alpha-CGRP. Nearly maximal effective concentrations of alpha
      CGRP (4 nM) and beta-CGRP (50 nM) caused stable relaxations of the temporal
      artery for 4 h without fading. BIBN4094BS antagonized the effects of alpha-CGRP
      (pK(B) = 10.1 and 9.9, respectively) more than beta-CGRP (pK(B) = 9.3 and 9.2
      respectively) on both temporal and occipital arteries. CGRP(8-37) antagonized the
      effects of alpha-CGRP (pK(B) = 6.6 and 6.4 respectively) more than beta-CGRP
      (pK(B) = 5.7 and 5.5 respectively) on both temporal and occipital arteries.
      Antagonism of the relaxant effects of alpha-CGRP (4 nM) and beta-CGRP (50 nM) by
      BIBN4096BS (10 and 100 nM) was reversible for beta-CGRP, but irreversible for
      alpha-CGRP, 1 h after BIBN4096BS washout. We conclude that alpha-CGRP and beta
      CGRP interact either at different binding sites of the same CGRP receptor system
      or all together with different receptor systems in human extracranial arteries.
      BIBN4096BS binds more firmly to the receptor activated by alpha-CGRP than to the
      receptor activated by beta-CGRP.

PMID- 15983762
TI  - Reflectometric interference spectroscopy combined with MALDI-TOF mass
      spectrometry to determine quantitative and qualitative binding of mixtures of
      vancomycin derivatives.
AB  - This paper describes the combination of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry with label free bio
      interaction analysis based on reflectometric interference spectroscopy (RIfS).
      The potential of this concerted approach is demonstrated by measuring the binding
      properties of different vancomycin-type glycopeptide antibiotic mixtures.
      Although RIfS is sensitive and does not require use of a label, it cannot
      determine which components of a mixture have bound to the surface after
      incubation. Fortunately, each bound species has a unique mass that can,
      afterwards, be determined by mass spectrometry. Thus, the screening capability of
      RIfS is combined with the identification capability of mass spectrometry.

PMID- 15983763
TI  - Arsenic speciation in xylem sap of cucumber (Cucumis sativus L.).
AB  - Flow injection analysis (FIA) and high-performance liquid chromatography double
      focusing sector field inductively coupled plasma mass spectrometry (HPLC-DF-ICP
      MS) were used for total arsenic determination and arsenic speciation of xylem sap
      of cucumber plants (Cucumis sativus L.) grown in hydroponics containing 2
      micromol dm(-3) arsenate or arsenite, respectively. Arsenite [As(III)], arsenate
      [As(V)] and dimethylarsinic acid (DMA) were identified in the sap of the plants.
      Arsenite was the predominant arsenic species in the xylem saps regardless of the
      type of arsenic treatment, and the following concentration order was determined:
      As(III) > As(V) > DMA. The amount of total As, calculated taking into
      consideration the mass of xylem sap collected, was almost equal for both
      treatments. Arsenite was taken up more easily by cucumber than arsenate. Partial
      oxidation of arsenite to arsenate (<10% in 48 h) was observed in the case of
      arsenite-containing nutrient solutions, which may explain the detection of
      arsenate in the saps of plants treated with arsenite.

PMID- 15983764
TI  - Uncertainty in aflatoxin B1 analysis using information from proficiency tests.
AB  - We describe how to calculate uncertainty in the determination of aflatoxin B(1)
      in nuts and maize using an HPLC method with prederivatisation with
      trifluoroacetic acid and fluorescence detection. The uncertainty is easily
      calculated using the information obtained from the participation in several
      proficiency tests. All the sources of uncertainty are grouped in two terms: (1)
      matrix variability, intermediate precision and sample heterogeneity, and (2)
      method concordance. This methodology has the advantage that no extra work needs
      to be done because all the information to calculate uncertainty comes from
      proficiency tests. The uncertainty values were calculated using samples whose
      concentration ranged between 2 and 20 microg L(-1). The relative standard
      uncertainty computed for aflatoxin B(1) was 16.3%.

PMID- 15983765
TI  - Application of cause-and-effect analysis to potentiometric titration.
AB  - A first attempt has been made to interpret physicochemical data from
      potentiometric titration analysis in accordance with the complete measurement
      uncertainty budget approach (bottom-up) of ISO and Eurachem. A cause-and-effect
      diagram is established and discussed. Titration data for arsenazo III are used as
      a basis for this discussion. The commercial software Superquad is used and
      applied within a computer-intensive resampling framework. The cause-and-effect
      diagram is applied to evaluation of seven protonation constants of arsenazo III
      in the pH range 2-10.7. The data interpretation is based on empirical probability
      distributions and their analysis by second-order correct confidence estimates.
      The evaluated data are applied in the calculation of a speciation diagram
      including uncertainty estimates using the probabilistic speciation software
      Ljungskile.

PMID- 15983766
TI  - Preparation of strong anion-exchange chromatographic packings based on
      monodisperse polymeric beads and their application in the separation of
      biopolymers.
AB  - A new hydrophilic strong anion-exchange (SAX) stationary phase for HPLC has been
      synthesized by chemical modification of macroporous 8.0-microm monodisperse
      poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads (P(GMA/EDMA)). The
      stationary phase was evaluated in detail to determine its ion-exchange
      properties, separability, reproducibility, hydrophilicity, and the effect of
      column loading and pH on the separation and retention of proteins. It was found
      to have an ion-exchange chromatographic (IEC) retention mechanism. The highest
      dynamic protein loading capacity of the synthesized SAX packing for BSA was 22.6
      mg g(-1). Five proteins were separated within 6.0 min using the synthesized SAX
      resin. The SAX resin was also used for rapid separation and purification of
      recombinant human stem cell factor (rhSCF) from a crude extract solution in only
      one step. The purity of the purified of rhSCF was >92.4%.

PMID- 15983767
TI  - Electroanalytical study of fluvoxamine.
AB  - Fluvoxamine (FVX) can be reduced at a mercury-drop electrode, with a maximum peak
      current intensity being obtained at a potential of -0.7 V vs. Ag/AgCl, in an
      aqueous electrolyte solution of pH 2. The compound was determined in a
      pharmaceutical product and in spiked human serum by square-wave adsorptive
      stripping voltammetry (SWAdSV) after accumulation at the electrode surface, under
      batch conditions. Because the presence of dissolved oxygen did not interfere
      significantly with the analysis, it was also possible to determine FVX in the
      pharmaceutical product by use of a flow-injection analysis (FIA) system with
      SWAdSV detection. The methods developed were validated and successfully applied
      to the quantification of FVX in a pharmaceutical product. Recoveries between 76
      and 89% were obtained in serum analysis. The FIA-SWAdSV method enabled analysis
      of up to 120 samples per hour at reduced cost, implying the possibility of
      competing with the chromatographic methods usually used for this analysis.

PMID- 15983768
TI  - Performance of calorimetric methods for the investigation of microbial systems in
      combination with additional sensors.
AB  - Calorimetric methods are used in combination with online oxygen measurement
      (using an amperometric sensor) and determination of the optical density (using a
      fibre optic sensor) to investigate microbial growth behaviour. The calorimetric
      curves of different batch experiments show a characteristic and reproducible
      course. Changes in the slope of the DeltaT-time curves indicate the effects of
      limiting factors on the microbial activity during the cultivation. A first
      limitation could be correlated with the depletion of oxygen in the medium; a
      second correlates with the depletion of the carbon source. Measurements of
      optical density in some cases provide reliable information about the growth of a
      microorganism culture. Our measurements show a good correlation of the universal
      calorimetric signal (heat-time curve) to the signal of the miniaturised
      photometric (OD) sensor.

PMID- 15983769
TI  - A quarter of a century of friendship.

PMID- 15983770
TI  - Effects of diclofenac on EPC liposome membrane properties.
AB  - In this work the interaction of a non-steroidal anti-inflammatory drug (NSAID),
      diclofenac, with egg yolk phosphatidylcoline (EPC) liposomes, used as cell
      membrane models, was quantified by determination of the partition coefficient.
      The liposome/aqueous phase partition coefficient was determined by derivative
      spectrophotometry, fluorescence quenching, and measurement of zeta-potential.
      Theoretical models based on simple partition of the diclofenac between two
      different media, were used to fit the experimental data, enabling the
      determination of K(p). The three techniques used yielded similar results. The
      effects of the interaction on the membrane's characteristics were further
      evaluated, either by studying membrane potential changes or by effects on
      membrane fluidity. The liposome membrane potential and the size and size
      homogeneity of liposomes were measured by light scattering. The effects of
      diclofenac on the internal viscosity or fluidity of the membrane were determined
      by use of spectroscopic probes-a series of n-(9-anthroyloxy) fatty acids in which
      the carboxyl terminal group is located at the interfacial region of the membrane
      and the fluorescent anthracene group is attached at different positions along the
      fatty acid chain. The location of the diclofenac on the membrane was also
      evaluated, by fluorescence quenching using the same series of fluorescent probes.
      Because the fluorescent anthracene group is attached at different positions along
      the fatty acid chain, it is possible to label at a graded series of depths in the
      bilayer. The interactions between the drug and the probe are a means of
      predicting the location of the drug on the membrane.

PMID- 15983771
TI  - The role of long-term and short-term familiarity in visual and haptic face
      recognition.
AB  - Recent studies have suggested that the familiarity of a face leads to more robust
      recognition, at least within the visual domain. The aim of our study was to
      investigate whether face familiarity resulted in a representation of faces that
      was easily shared across the sensory modalities. In Experiment 1, we tested
      whether haptic recognition of a highly familiar face (one's own face) was as
      efficient as visual recognition. Our observers were unable to recognise their own
      face models from tactile memory alone but were able to recognise their faces
      visually. However, haptic recognition improved when participants were primed by
      their own live face. In Experiment 2, we found that short-term familiarisation
      with a set of previously unfamiliar face stimuli improved crossmodal recognition
      relative to the recognition of unfamiliar faces. Our findings suggest that
      familiarisation provides a strong representation of faces but that the nature of
      the information encoded during learning is critical for efficient crossmodal
      recognition.

PMID- 15983772
TI  - Time-of-flight magnetic resonance angiography in the follow-up of intracranial
      aneurysms treated with Guglielmi detachable coils.
AB  - The purpose of this study was to evaluate time-of-flight magnetic resonance
      angiography (MRA) in the follow-up of intracranial aneurysms treated with
      Guglielmi detachable coils (GDCs). From January 1998 to January 2002 27 MRA and
      intra-arterial digital subtraction angiography (IADSA) examinations were analyzed
      for residual aneurysms and arterial patency following GDC placement. A total
      number of 33 intracranial aneurysms was analyzed, including 18 located in the
      posterior circulation. The MRA analysis was based on source images in combination
      with maximum intensity projections. The IADSA was used as the reference standard.
      Two aneurysms were excluded from evaluation, because of susceptibility artefacts
      from other aneurysms, which were clipped. Sensitivity and positive predictive
      values of MRA in revealing residual aneurysms were, respectively, 89% and 80%.
      Specificity in ruling out remnant necks and residual flow around coils was,
      respectively, 91% and 97%, with a negative predictive value of, respectively, 95%
      and 100%. Specificity and negative predictive value of MRA for arterial occlusion
      were, respectively, 87% and 100% for the parent arteries and, respectively, 85%
      and 100% for the adjacent arteries. MRA is a reliable diagnostic tool in the
      follow-up of GDC treatment, and it may replace IADSA in excluding residual flow
      around coils and aneurysmal necks and in ruling out arterial occlusion.

PMID- 15983773
TI  - Rescue localized intra-arterial thrombolysis for hyperacute MCA ischemic stroke
      patients after early non-responsive intravenous tissue plasminogen activator
      therapy.
AB  - The outcome of patients who show no early response to intravenous (i.v.) tissue
      plasminogen activator (tPA) therapy is poor. The objective of this study was to
      evaluate the feasibility of rescue localized intra-arterial thrombolysis (LIT)
      therapy for acute ischemic stroke patients after an early non-responsive i.v. tPA
      therapy. Patients with proximal MCA occlusions who were treated by LIT (n = 10)
      after failure of early response [no improvement or improvement of National
      Institute of Health Stroke Scale (NIHSS) scores of < or = 3] to i.v. tPA therapy
      (0.9 mg/kg-10% bolus and 90% i.v. infusion over 60 min) were selected. The
      recanalization rates, incidence of post-thrombolysis hemorrhage and clinical
      outcomes [baseline and discharge NIHSS scores, mortality, 3 months Barthel index
      (BI) and modified Rankin score (mRS)] were evaluated. Rescue LIT therapy was
      performed on ten MCA occlusion patients (male:female = 3:7, mean age 71 years).
      The mean time between the initiation of i.v. tPA therapy and the initiation of
      intra-arterial urokinase (i.a. UK) was 117+/-25.0 min [time to i.v. tPA 137+/-32
      min; time to digital subtraction angiography (DSA) 221+/-42 min; time to i.a. UK
      260+/-46 min]. The baseline NIHSS scores showed significant improvement at
      discharge (median from 18 to 6). Symptomatic hemorrhage and, consequent,
      mortality were noted in 2/10 (20%) patients. Three months good outcome was noted
      in 4/10 (40%, mRS 0-2) and 3/10 (30%, BI > or = 95). In conclusion, rescue LIT
      therapy can be considered as a treatment option for patients not showing early
      response to full dose i.v. tPA therapy. Larger scale studies for further
      validation of this protocol may be necessary.

PMID- 15983774
TI  - Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography
      and MRI findings.
AB  - Beckwith-Wiedemann syndrome is characterized by a group of clinical
      abnormalities, the most frequent of which are omphalocele, macroglossia,
      gigantism, neonatal hypoglycemia and umbilical hernia. The association of this
      syndrome with malignant tumors is well documented. We report a child with this
      syndrome associated with bilateral adrenal pheochromocytoma.

PMID- 15983775
TI  - Combined SPECT/CT imaging using 123I-IMT in the detection of recurrent or
      persistent head and neck cancer.
AB  - The aim of the study was to assess the clinical value of combined SPECT/CT
      imaging using L: -3-[123I]iodine-alpha-methyl tyrosine (IMT) for the differential
      diagnosis of recurrences in patients pre-treated for head and neck cancer. Thirty
      four consecutive patients with biopsy-proven carcinomas, who had previously been
      treated by surgery and/or radio/chemotherapy, were examined at our clinic by IMT
      SPECT using a dual-head system with integrated low-dose CT. SPECT results were
      correlated with histopathology, clinical and CT/MRI follow-up data. In the follow
      up after SPECT examination, the final diagnosis of recurrent tumour was
      established in 26 patients; the remaining eight patients were recurrence-free
      (follow-up >6 months). IMT-SPECT/CT correctly detected recurrent disease and/or
      neck lymph node metastases in 22 patients. In addition, distant metastases were
      displayed in two patients. The study was false-negative in four patients
      (sensitivity 85%). True-negative results were registered in seven patients, and
      false-positive in one patient. Image fusion with coregistered low-dose CT
      facilitates the localisation and interpretation of IMT-SPECT findings. IMT-SPECT
      using integrated low-dose CT is a promising non-invasive imaging tool for the
      detection of head and neck cancer recurrences and their differentiation from
      treatment-induced changes.

PMID- 15983776
TI  - Contemporary imaging techniques for the diagnosis of renal artery stenosis.
AB  - Renal artery stenosis (RAS) is a potentially curable cause of renovascular
      hypertension (RVH) and is caused by either atherosclerosis or fibromuscular
      dysplasia (FMD) in the vast majority of patients. Although intra-arterial digital
      subtraction angiography (IA-DSA) is still considered the standard of reference
      test for the anatomical diagnosis of RAS, noninvasive techniques such as MR
      angiography, CT angiography, and color-aided duplex ultrasonography are promising
      alternatives that also allow functional characterization of RAS. We provide an
      overview of these techniques and discuss their relative merits and shortcomings.
      Analysis of high-quality studies shows that both MR and CT angiography are
      significantly more accurate for the diagnosis of at least 50% atherosclerotic RAS
      than ultrasonographic techniques. The primary strength of ultrasonography at
      present is its suggested ability to predict functional recovery based on
      preinterventional resistance index measurements. A still unresolved issue is the
      detection of FMD. Because missing RVH may have serious consequences the most
      important requirement for a screening test is that it has high sensitivity.

PMID- 15983777
TI  - Assessment of MRI and MRCP in diagnosis of biliary cystadenoma and
      cystadenocarcinoma.
AB  - Magnetic resonance imaging (MRI) and magnetic resonance cholangio-pancreatography
      (MRCP) features were analyzed in the diagnosis of seven surgically resected
      hepatobiliary cystic tumors with reference to histopathological data.
      Homogeneity, size, location, signal intensity, presence or absence of septa
      and/or nodules and MRCP features of the lesions were studied. Histological
      evidence demonstrated six biliary cystadenoma (BCA) including four pseudo-ovarian
      stroma (POS) and one biliary cystadenocarcinoma (BCAC). Cystic lesions (3-15 cm
      in diameter) were homogeneous in the six BCA, heterogeneous in the one BCAC, and
      were located in the left and right liver, respectively. On T2-weighted images all
      lesions were hyperintense. On T1-weighted images hypointensity was found in three
      BCA (all serous fluid, including one POS), isointensity was found in the three
      others (two mucinous and one hemorrhagic fluid, including three POS) and in the
      one BCAC (containing mucinous fluid). Septas were present in all cases and
      nodules only in the one BCAC. On MRCP a hyperintense cystic lesion was found in
      all cases and a bile ducts dilatation in two BCA and the one BCAC. Gadolinium
      enhanced MRI in combination with MRCP is a valuable tool for the diagnosis of BCA
      or BCAC. However, no specific information is gained for POS detection.

PMID- 15983778
TI  - [OCT-goniometry before and after iridotomy in angle-closure glaucoma].
AB  - PURPOSE: Visualization of the anterior chamber angle is an important diagnostic
      method in patients with angle-closure glaucoma. In this study, optical coherence
      tomography (OCT) was used to image the angle width, the iris configuration, and
      the iris thickness in patients with angle-closure glaucoma. METHODS: Thirteen
      eyes of 11 patients suffering from angle-closure glaucoma were studied with
      slitlamp-adapted OCT. All patients were treated with Nd:YAG laser iridotomy. The
      angle width ( degrees ), the angle opening distance (AOD) (microm), and the iris
      thickness (microm) were measured with OCT. The configuration of the iris was
      classified as steeply convex, convex, or flat. RESULTS: The mean angle width was
      preoperatively 5.1+/-5.0 degrees (0-15 degrees ) and enlarged significantly
      (p=0.007) to 10.4+/-5.5 degrees (0-19 degrees ) postoperatively. The AOD changed
      from 71+/-55 microm (0-157 microm) preoperatively to 143+/-74 microm (0-256
      microm) postoperatively (p<0.001). The mean iris thickness was 338+/-33 microm.
      With the exception of two eyes the predominant iris configuration changed from
      convex to flat. CONCLUSIONS: OCT allowed visualization and noninvasive assessment
      of the anterior chamber angle region in patients with angle-closure glaucoma. Our
      results suggest that goniometry with OCT could improve the evaluation in patients
      with narrow or closed anterior chamber angles.

PMID- 15983779
TI  - [Quantitative evaluation of acrylic and silicone intraocular lenses with a sharp
      optic edge design].
AB  - BACKGROUND: At the Department of Ophthalmology, Heidelberg, Germany, posterior
      capsule opacification (PCO) of a silicone and an acrylic intraocular lens (IOL)
      with a sharp optic edge design was evaluated. PATIENTS AND METHODS: In a
      prospective study either the AMO ClariFlex silicone IOL or the Sensar AR40e
      hydrophobic acrylic IOL were implanted in 47 patients following uneventful
      phacoemulsification. Mean patient age was 76.2+/-7.8 (ClariFlex) and 73.4+/-12.9
      years (AR40e), respectively. The mean follow-up time was 19.7+/-5.34 in the
      ClariFlex and 21.9+/-1.89 months in the AR40e group. PCO development was
      evaluated postoperatively using the EPCO 2000 analysis software (scale 0-4).
      Areas of interest were the total IOL optic, the central 3-mm zone as well as the
      capsulorhexis. RESULTS: In both groups, all patients achieved a BCVA of 20/32
      (AR40e) and 20/25 (ClariFlex), respectively. There was a very low incidence of
      PCO development with a mean EPCO score of 0.07+/-0.2 (ClariFlex and 0.15+/-0.2
      (AR40e). Within the 3-mm zone and the capsulorhexis, there was a tendency for
      even lower EPCO scores in both groups. We calculated a statistically significant
      difference for the two lens materials for all investigated IOL areas (Wilcoxon's
      test, p<0.05). CONCLUSION: Both IOLs with a sharp edge design showed good
      functional results, a stable position in the capsular bag as well as a low
      incidence of PCO development. However, the silicone IOL showed statistically
      significantly lower PCO scores.

PMID- 15983780
TI  - Will intra-operative measurement of parathyroid hormone alter the surgical
      concept of renal hyperparathyroidism?

PMID- 15983782
TI  - TGFbeta signalling in the development of ovarian function.
AB  - Ovarian development begins back in the embryo with the formation of primordial
      germ cells and their subsequent migration and colonisation of the genital ridges.
      Once the ovary has been defined structurally, the primordial germ cells transform
      into oocytes and become housed in structures called follicles (in this case,
      primordial follicles), a procedure that, in most mammals, occurs either shortly
      before or during the first few days after birth. The growth and differentiation
      of follicles from the primordial population is termed folliculogenesis.
      Primordial follicles give rise to primary follicles that transform into preantral
      follicles, then antral follicles (secondary follicles) and, finally
      (preovulatory) Graafian follicles (tertiary follicles) in a co-ordinated series
      of transitions regulated by hormones and local intraovarian factors. Members of
      the transforming growth factor-beta (TGFbeta) superfamily have been shown to play
      important roles in this developmental process starting with the specification of
      primordial germ cells by the bone morphogenetic proteins through to the
      recruitment of primordial follicles by anti-Mullerian hormone and, potentially,
      growth and differentiation factor-9 (GDF9) and, finally, their transformation
      into preantral and antral follicles in response to activin and TGF-beta.
      Developmental and mutant mouse models have been used to show the importance of
      this family of growth factors in establishing the first wave of folliculogenesis.

PMID- 15983781
TI  - A systematic analysis of LINE-1 endonuclease-dependent retrotranspositional
      events causing human genetic disease.
AB  - Diverse long interspersed element-1 (LINE-1 or L1)-dependent mutational
      mechanisms have been extensively studied with respect to L1 and Alu elements
      engineered for retrotransposition in cultured cells and/or in genome-wide
      analyses. To what extent the in vitro studies can be held to accurately reflect
      in vivo events in the human genome, however, remains to be clarified. We have
      attempted to address this question by means of a systematic analysis of recent L1
      mediated retrotranspositional events that have caused human genetic disease, with
      a view to providing a more complete picture of how L1-mediated retrotransposition
      impacts upon the architecture of the human genome. A total of 48 such mutations
      were identified, including those described as L1-mediated retrotransposons, as
      well as insertions reported to contain a poly(A) tail: 26 were L1 trans-driven
      Alu insertions, 15 were direct L1 insertions, four were L1 trans-driven SVA
      insertions, and three were associated with simple poly(A) insertions. The
      systematic study of these lesions, when combined with previous in vitro and
      genome-wide analyses, has strengthened several important conclusions regarding L1
      mediated retrotransposition in humans: (a) approximately 25% of L1 insertions are
      associated with the 3' transduction of adjacent genomic sequences, (b)
      approximately 25% of the new L1 inserts are full-length, (c) poly(A) tail length
      correlates inversely with the age of the element, and (d) the length of target
      site duplication in vivo is rarely longer than 20 bp. Our analysis also suggests
      that some 10% of L1-mediated retrotranspositional events are associated with
      significant genomic deletions in humans. Finally, the identification of
      independent retrotranspositional events that have integrated at the same genomic
      locations provides new insight into the L1-mediated insertional process in
      humans.

PMID- 15983783
TI  - [Pain processing in patients with borderline personality disorder, fibromyalgia,
      and post-traumatic stress disorder].
AB  - The authors review relevant experimental studies on pain perception and
      processing in psychiatric disorders with traumatic stress as an etiological
      factor. In borderline personality disorder, post-traumatic stress disorder, and
      fibromyalgia neurophysiological and neuropsychological patterns of pain
      processing appear to be different. Experimental studies in borderline patients
      show a desensitization of pain thresholds whereas patients with fibromyalgia show
      an opposite pattern, which could be explained by a central augmentation of pain
      processing. Furthermore, the authors outline methods to assess pain perception
      (peripheral and central) and describe the neurobiological mechanisms of pain
      processing, particularly the distinction between the sensory-discriminative
      lateral system and the affective-motivational medial system. Finally, suggestions
      for further research and implications for therapy are proposed.

PMID- 15983784
TI  - Transiently enhanced LPS-induced fever following hyperthermic stress in rabbits.
AB  - Hyperthermia has been shown to induce an enhanced febrile response to the
      bacterial-derived endotoxin lipopolysaccharide (LPS). The aim of the present
      study was to test the hypothesis that the enhanced LPS-induced fever seen in heat
      stressed (HS) animals is caused by leakage of intestinal bacterial LPS into the
      circulation. Male rabbits were rendered transiently hyperthermic (a maximum
      rectal temperature of 43 degrees C) and divided into three groups. They were then
      allowed to recover in a room at 24 degrees C for 1, 2 or 3 days post-HS. One day
      after injection with LPS, the post-HS rabbits exhibited significantly higher
      fevers than the controls, though this was not seen in rabbits at either 2 or 3
      days post-HS. The plasma levels of endogenous LPS were significantly increased
      during the HS as compared to those seen in normothermic rabbits prior to HS. LPS
      fevers were not induced in these animals. One day post-HS, rabbits that had been
      pretreated with oral antibiotics exhibited significantly attenuated LPS levels.
      When challenged with human recombinant interleukin-1beta instead of LPS, the 1
      day post-HS rabbits did not respond with enhanced fevers. The plasma levels of
      TNFalpha increased similarly during LPS-induced fevers in both the control and 1
      day post-HS rabbits, while the plasma levels of corticosterone and the osmolality
      of the 1-day post-HS rabbits showed no significant differences to those seen
      prior to the HS. These results suggest that the enhanced fever in the 1-day post
      HS rabbits is LPS specific, and may be caused by increased leakage of intestinal
      endotoxin into blood circulation.

PMID- 15983785
TI  - Wheat genome structure: translocations during the course of polyploidization.
AB  - The genomic organization of Triticum timopheevii (2n=28, AtAtGG) was compared
      with hexaploid wheat T. aestivum (2n=42, AABBDD) by comparative mapping using
      microsatellites derived from bread wheat. Genetic maps for the two crosses T.
      timopheevii var. timopheevii x T. timopheevii var. typica and T. timopheevii K
      38555xT. militinae were constructed. On the first population, 121 loci were
      mapped, and on the second population 103 loci. The transferability of the wheat
      markers to T. timopheevii was generally better for the A genome-specific markers
      (76-78% produced amplification products; 26 and 29% were polymorphic) than for B
      genome-specific markers (54% produced amplification products; 14 and 16% were
      polymorphic). Of the D genome-specific markers, one third produced amplification
      products in T. timopheevii, but only 5 and 2% were polymorphic in the
      corresponding mapping populations. The maps constructed confirmed the previously
      described translocation between chromosome arms 6AtS and 1GS and revealed at
      least two yet unknown rearrangements on chromosomes 4At and 6At09. The presence
      of other translocations and rearrangements between T. timopheevii and T. aestivum
      was demonstrated by a variety of markers mapping to nonhomoeologous positions.

PMID- 15983786
TI  - Hallucinogen-like actions of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T
      7) in mice and rats.
AB  - RATIONALE: Few studies have examined the effects of 2,5-dimethoxy-4-(n)
      propylthiophenethylamine (2C-T-7) in vivo. OBJECTIVES: 2C-T-7 was tested in a
      drug-elicited head twitch assay in mice and in several drug discrimination assays
      in rats; 2C-T-7 was compared to the phenylisopropylamine hallucinogen R(-)-1-(2,5
      dimethoxy-4-methylphenyl)-2aminopropane (DOM) in both assays, with or without
      pretreatment with the selective 5-HT2A antagonist (+)-(2,3-dimethoxyphenyl)-1-[2
      (4-fluorophenylethyl)]-4-piperidine-methanol (M100907). Finally, the affinity of
      2C-T-7 for three distinct 5-HT receptors was determined in rat brain. METHODS:
      Drug-elicited head twitches were quantified for 10 min following administration
      of various doses of either 2C-T-7 or R(-)-DOM, with and without pretreatments of
      0.01 mg/kg M100907. In rats trained to discriminate lysergic acid diethylamide
      (LSD), 2C-T-7 and R(-)-DOM were tested for generalization. In further studies,
      rats were trained to discriminate 2C-T-7 from saline, then challenged with 0.05
      mg/kg M100907. In competition binding studies, the affinity of 2C-T-7 was
      assessed at 5-HT2A receptors, 5-HT1A receptors, and 5-HT2C receptors. RESULTS: 2C
      T-7 and R(-)-DOM induced similar head twitch responses in the mouse that were
      antagonized by M100907. In the rat, 2C-T-7 produced an intermediate degree of
      generalization (75%) to the LSD cue and served as a discriminative stimulus;
      these interoceptive effects were attenuated by M100907. Finally, 2C-T-7 had
      nanomolar affinity for 5-HT2A and 5-HT2C receptors and lower affinity for 5-HT1A
      receptors. CONCLUSIONS: 2C-T-7 is effective in two rodent models of 5-HT2 agonist
      activity and has affinity at receptors relevant to hallucinogen effects. The
      effectiveness with which M100907 antagonizes the behavioral actions of 2C-T-7
      strongly suggests that the 5-HT2A receptor is an important site of action for
      this compound.

PMID- 15983787
TI  - Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and
      its enantiomers in the mouse.
AB  - RATIONALE: Drug challenges in "intact" and p-chlorophenylalanine (p-CPA)-treated
      animals can be used to distinguish agents that act as direct serotonin (5-HT)
      agonists from agents that function as 5-HT releasers. OBJECTIVES: The objective
      of the study was to investigate the effect of p-CPA treatment on the capacity of
      racemic 3,4-methylenedioxymethamphetamine (MDMA) and its stereoisomers to induce
      the head twitch response, hyperthermia, and locomotor stimulation in mice.
      METHODS: Pretreatments with either 100 mg/kg p-CPA or equivolume saline were
      administered for three consecutive days. The following day, mice were either
      euthanized (to quantify 5-HT tone), tested with various doses of racemic MDMA or
      one of its enantiomers in the head twitch assay, or challenged with 32 mg/kg
      racemic MDMA or one of its enantiomers, while temperature and locomotor activity
      were monitored via radiotelemetry. RESULTS: p-CPA reduced cortical 5-HT turnover
      by >70% without altering dopamine turnover. Racemic MDMA did not induce a
      significant head twitch response in intact or p-CPA-treated mice. S(+)-MDMA and
      R(-)-MDMA elicited similar head twitch curves in intact mice; p-CPA treatment
      attenuated this response when induced by S(+)-MDMA but not when elicited by R(-)
      MDMA. Neither the hyperthermic nor locomotor-stimulant effects of racemic MDMA
      were altered by p-CPA treatment. The hyperthermic effects, but not the locomotor
      stimulant effects, of S(+)-MDMA were attenuated in mice treated with p-CPA. R(-)
      MDMA did not alter core temperature or induce significant locomotor stimulation
      in intact or p-CPA-treated mice. CONCLUSIONS: The effects of S(+)-MDMA on core
      temperature and head twitch behavior are consistent with a mechanism involving 5
      HT release, whereas the effects of R(-)-MDMA on head twitch behavior are
      consistent with a direct agonist mechanism of action. The actions of the racemate
      on core temperature and locomotor activity likely involve a combination of 5-HT
      release and direct agonism at 5-HT receptors.

PMID- 15983788
TI  - Attentional bias for caffeine-related stimuli in high but not moderate or non
      caffeine consumers.
AB  - RATIONALE: Attentional bias for drug-related cues has been reported with a wide
      range of drugs, but to date the extent to which caffeine consumers show similar
      biases for caffeine-related stimuli has not been tested. The present study
      therefore examined this issue in terms of differences in attentional bias for
      caffeine-related words in High, Moderate and Non-caffeine consumers using a dot
      probe word task following overnight caffeine abstinence. OBJECTIVES: This study
      was conducted to test whether caffeine consumers show an attentional bias for
      caffeine-related words, and whether such biases relate to habitual levels of
      caffeine use. METHODS: Sixteen High, Moderate and Non-consumers of caffeine were
      asked to complete a modified dot-probe task in order to measure attentional bias
      for caffeine-related relative to neutral control word groups. The task was
      completed following overnight caffeine abstinence, and participants also
      completed mood and caffeine-craving measures. RESULTS: The High consumer group
      showed a significant attentional bias for the caffeine-related words, but no such
      bias was seen in Moderate or Non-consumer groups. As expected, craving for
      caffeine was strongest in the High consumers and weakest in the Non-consumers.
      Attentional bias in the High group correlated with self-reported caffeine
      consumption and with craving for caffeine, but neither effect was significant in
      the Moderate group. CONCLUSIONS: These data confirm that High caffeine consumers
      show attentional bias for caffeine-related stimuli, consistent with current
      theories of drug addiction.

PMID- 15983789
TI  - Negative GABA(A) modulators attenuate the discriminative stimulus effects of
      benzodiazepines and the neuroactive steroid pregnanolone in rhesus monkeys.
AB  - RATIONALE: Negative GABA(A) modulators (i.e., inverse agonists) might be useful
      for identifying mechanisms at the GABA(A) receptor complex that mediate the
      effects of positive GABA(A) modulators, especially those for which there are no
      available competitive antagonists. OBJECTIVE: Drug discrimination was used to
      examine antagonism of a 5-beta neuroactive steroid (pregnanolone) and a
      benzodiazepine (midazolam) by several negative GABA(A) modulators in rhesus
      monkeys. METHODS: One group of monkeys (n=5) received 5.6 mg kg(-1) day(-1) of
      diazepam (p.o.) and discriminated the benzodiazepine antagonist flumazenil (0.1
      or 0.32 mg/kg s.c.); another group of monkeys (n=5) discriminated the
      benzodiazepine midazolam (0.32 mg/kg s.c.). RESULTS: In diazepam-treated monkeys,
      negative GABA(A) modulators with increasing efficacy, including Ro 15-4513, ethyl
      beta-carboline-3-carboxylate (beta-CCE), methyl beta-carboline-3-carboxylate
      (beta-CCM) and methyl-6,7-dimethoxyl-4-ethyl-beta-carboline-3-carboxylate (DMCM),
      substituted for flumazenil. In monkeys discriminating midazolam, pregnanolone
      occasioned high levels of midazolam-lever responding, and these effects were
      attenuated by beta-CCE and beta-CCM, but not by flumazenil, Ro 15-4513, or DMCM.
      The midazolam discriminative stimulus also was attenuated by beta-CCM and DMCM;
      Schild analysis was consistent with a simple competitive interaction between
      midazolam and beta-CCM but not between midazolam and DMCM. CONCLUSIONS: Negative
      modulators are qualitatively similar to neutral modulators in diazepam-treated
      animals; however, interactions between negative modulators and midazolam suggest
      that different receptors mediate the effects of some (DMCM) and not other (beta
      CCM) negative modulators. Negative modulators at benzodiazepine sites exert
      efficacy-dependent antagonism of positive modulators at neuroactive steroid
      sites. Without competitive antagonists at neuroactive steroid or barbiturate
      sites, negative modulators could prove useful for examining the mechanism of
      action of different classes of positive GABA(A) modulator.

PMID- 15983790
TI  - Processing efficiency of a verbal working memory system is modulated by
      amphetamine: an fMRI investigation.
AB  - RATIONALE: Working memory performance may be improved or decreased by
      amphetamine, depending on baseline working memory capacity and amphetamine
      dosage. This variable effect suggests an optimal range of monaminergic activity
      for working memory, either below or above which it is compromised. We directly
      tested this possibility with human participants by varying amphetamine dosage and
      measuring the efficiency of cortical processing in brain regions associated with
      working memory. OBJECTIVES: The modulation of cortical processing in a verbal
      working memory network by dextroamphetamine (D-amph) was examined using BOLD
      functional magnetic resonance imaging (fMRI) with healthy participants. The goal
      of the study was to test the hypothesis of an inverted U-shaped relationship
      between D-amph dose and processing efficiency of a verbal working memory system.
      METHODS: D-amph dosage was increased cumulatively every 2 h across four scanning
      sessions collected in a single day. The primary measure used for analyses in this
      study was the extent of activation in brain regions empirically defined as a
      working memory network. RESULTS: An inverted U-shaped relationship was observed
      between the amount of D-amph administered and working memory processing
      efficiency. This relationship was specific to brain areas functionally defined as
      working memory regions and to the encoding/maintenance phase (as opposed to the
      response phase) of the task. CONCLUSION: The results are consistent with the
      hypothesis that the neurochemical effects of amphetamine modulate the efficiency
      of a verbal working memory system. The effect of amphetamine on working memory in
      healthy individuals may provide insight regarding the working memory deficits
      seen in schizophrenia, given the overlap between neurochemical systems affected
      by amphetamine, and those disordered in schizophrenia.

PMID- 15983791
TI  - Hyperactivity, impaired learning on a vigilance task, and a differential response
      to methylphenidate in the TRbetaPV knock-in mouse.
AB  - RATIONALE: The thyroid hormones (T3 and T4) play a critical role in brain
      development, and thyroid abnormalities have been linked to a variety of
      psychiatric and neuropsychological disorders. Among patients with the rare
      genetic syndrome resistance to thyroid hormone (RTH), 40-70% meet the diagnostic
      criteria for attention deficit-hyperactivity disorder (ADHD). RTH is caused by a
      mutation in the thyroid receptor beta (Thrb) gene that results in reduced binding
      of T3 to its receptor and elevated concentrations of T3, T4, and thyroid
      stimulating hormone. OBJECTIVES: We tested a knock-in (KI) mouse expressing a
      mutant TRbeta allele (TRbetaPV) for the behavioral features of ADHD and their
      response to methylphenidate (MPH). METHODS: The locomotor activity of the
      TRbetaPV KI mice was measured in activity monitors over multiple sessions.
      Sustained attention and the effects of MPH on attention were assessed using a
      vigilance task. RESULTS: The TRbetaPV KI mice are hyperactive and have learning
      deficits on a vigilance task. Doses of MPH that impair the vigilance performance
      of wild-type mice do not affect the performance of the TRbetaPV KI mice.
      CONCLUSIONS: The TRbetaPV KI mice provide a tool for studying the underlying
      neural deficits that contribute to thyroid-related neurological disorders,
      hyperactivity, and altered responsiveness to MPH.

PMID- 15983792
TI  - Methylphenidate increases cigarette smoking.
AB  - RATIONALE: Methylphenidate (Ritalin) and d-amphetamine (Dexedrine), stimulants
      commonly prescribed for behavioral problems associated with attention deficit
      hyperactivity disorder (ADHD), produce a similar constellation of behavioral
      effects. The results of previous studies suggest that d-amphetamine increases
      rates of smoking and the reinforcing effects of smoking. The effects of
      methylphenidate on smoking have not been assessed although it is the most
      commonly prescribed pharmacotherapy for ADHD and individuals with ADHD are at
      increased risk for smoking. OBJECTIVE: In this experiment the acute effects of a
      range of doses of methylphenidate (5, 10, 20, and 40 mg) and placebo were
      assessed in ten cigarette smokers who were not attempting to quit and were
      without ADHD or other Axis I psychiatric disorders. METHODS: Each dose of
      methylphenidate was tested once, whereas placebo was tested twice. One hour after
      ingesting drug, participants were allowed to smoke ad libitum for 4 h. Measures
      of smoking included total cigarettes smoked, total puffs, latency to the first
      cigarette, and carbon monoxide levels. Snacks and decaffeinated drinks were
      available ad libitum, and caloric intake during the 4-h smoking session was
      calculated. RESULTS: Methylphenidate dose dependently increased the total number
      of cigarettes smoked, number of puffs, and carbon monoxide levels. As expected,
      methylphenidate dose dependently decreased the number of food items consumed and
      caloric intake. CONCLUSIONS: The results of this experiment suggest that
      methylphenidate, like d-amphetamine, increases rates of cigarette smoking.

PMID- 15983793
TI  - Visualisation of the cortical dopamine D3 receptors in alcoholics and controls
      with human whole-hemisphere autoradiography.

PMID- 15983794
TI  - Combined D1/D2 receptor stimulation under conditions of dopamine depletion
      impairs spatial working memory performance in humans.
AB  - RATIONALE: The mesocortical dopamine system is regarded as an important modulator
      of working memory. While it has been established that stimulation of the D1/D2
      receptor in primates can improve spatial working memory performance, findings in
      humans are less consistent. Recent studies in humans suggest that global
      depletion of dopamine via tyrosine/phenylalanine depletion may impair spatial
      working memory performance, although these results are also inconsistent, and it
      has been suggested that task differences may partly underlie the inconsistent
      findings. OBJECTIVES: This study had two aims: (1) to investigate the effects of
      acute tyrosine depletion (TPD) on a number of working memory tasks and (2) to
      examine whether stimulation of D1/D2 receptors under conditions of TPD can
      attenuate or "reverse" TPD-induced working memory impairments. METHODS: Eighteen
      healthy male participants performed a spatial working memory delayed-recognition
      task, non-spatial working memory task and spatial n-back task on three separate
      occasions, after TPD, TPD and pergolide (D1/D2 agonist), and placebo. RESULTS:
      TPD did not impair working memory performance on any of the tasks administered.
      However, stimulation of D1/D2 receptors under TPD conditions caused a subtle
      impairment in spatial working memory performance. CONCLUSIONS: The finding that
      D1/D2 stimulation under TPD conditions impairs working memory highlights the
      complexity of functional effects of augmenting dopaminergic transmission within a
      dopamine-depleted state. The lack of TPD-related effects on a range of working
      memory tasks questions the reliability of TPD as a modulator of dopamine function
      and working memory performance in humans.

PMID- 15983795
TI  - Antidepressants differentially affect expression of complexin I and II RNA in rat
      hippocampus.
AB  - Disturbance of synaptic transmission is currently viewed as an important
      pathophysiological mechanism and therapeutic target of mood disorders. Amongst
      other lines of evidence this theory is based on human post-mortem investigations
      showing differential expression of complexins. In order to discriminate between
      molecular correlates of the disease itself and effects of psychotropic drugs
      given to patients, we performed an animal trial using subchronic antidepressant
      treatment. Cohorts of adult male Sprague-Dawley rats were treated over a period
      of 14 days with intraperitoneal injections of either saline (0.9%, n=8),
      desipramine (15 mg/kg, n=7), fluoxetine (10 mg/kg, n=8), or tranylcypromine (10
      mg/kg, n=5). Brain slices were used for in situ hybridizations with 35S labelled
      RNA probes of the genes complexin I, complexin II and syntaxin 1 A, the SNARE
      complex protein interacting with the complexins, and assessed semi-quantitatively
      for region-specific expression levels. Expression of complexin I was induced only
      in habenular nuclei after treatment with fluoxetine. In contrast, complexin II
      was significantly induced by desipramine and tranylcypromine, but not fluoxetine,
      in several brain regions. All treatment groups, but most significantly fluoxetine
      treated animals, showed higher expression levels of syntaxin 1A. Antidepressants
      differentially affect expression levels of complexin I and more prominently
      complexin II and syntaxin 1A. The induction of complexin II and syntaxin 1A might
      strengthen the synaptic transmission at axo-dendritic or axo-axonal synapses.
      Previous post-mortem findings reporting on downregulation of complexins cannot be
      explained as mere effects of psychotropic drug treatment.

PMID- 15983796
TI  - Acute administration of the novel serotonin and noradrenaline reuptake inhibitor,
      S33005, markedly modifies sleep-wake cycle architecture in the rat.
AB  - RATIONALE: The interrelationship between depressive states and sleep-wake cycle
      architecture is characterised by a decreased latency to the first paradoxical
      sleep (PS) episode, together with an enhancement of PS during the first part of
      the night. Conversely, slow-wave sleep (SWS) is decreased and intermittent
      awakenings increased. Notably, antidepressant treatment is generally associated
      with a diminution of PS. OBJECTIVES: In light of these observations, we examined
      the influence of acute administration of the novel mixed serotonin-noradrenaline
      reuptake blocker, (-)1-(1-dimethylaminomethyl 5-methoxybenzocyclobutan-1-yl)
      cyclohexanol HCl (S33005), upon sleep-wake architecture in rats. METHODS: Animals
      were injected with vehicle or incremental doses of S33005 at the onset of either
      the dark or light periods. Digitised polygraphic recordings were performed, and
      changes evoked by S33005 were determined over 24-h recording periods, i.e.,
      number and duration of sleep-wake episodes, latencies to PS and SWS, power band
      spectra of the electroencephalogram (EEG) and circadian changes. RESULTS: At 0.04
      mg/kg, S33005 was inactive, whereas at 0.63 mg/kg, it modestly increased PS
      latencies and diminished PS duration during the light period. At 10 mg/kg, S33005
      reduced markedly PS duration for about 4-h when injected prior to both light and
      dark periods. Latency to PS was prolonged, and the circadian acrophase was
      delayed. These effects are in keeping with previous studies of monoamine reuptake
      inhibitors, but, notably, SWS duration was increased when S33005 was injected at
      the onset of the light phase (+4%). These changes occurred without marked
      modifications in circadian rhythmicity or EEG spectral band power. Finally, even
      at the highest dose of S33005, only a limited rebound of SWS (+5%) and PS (+10%)
      was apparent. Amongst antidepressant to date examined, this is an original
      profile of influence upon sleep patterns. CONCLUSIONS: These results demonstrate
      a pattern of influence of S33005 upon sleep-wake architecture in rats which is
      globally consistent with antidepressant properties, but with a distinctive
      enhancement of restorative slow-wave sleep.

PMID- 15983797
TI  - Blockade of adenosine and dopamine receptors inhibits the development of rapid
      tolerance to ethanol in mice.
AB  - RATIONALE: Several reports have suggested the involvement of brain adenosine and
      dopamine receptors in different actions produced by ethanol such as motor
      incoordination or anxiolytic, hypnotic and reinforcing effects. The co
      localization and interaction between adenosine and dopamine receptors in
      different brain regions has also been well documented. However, few studies have
      demonstrated the involvement of these mechanisms in the tolerance induced by
      ethanol. OBJECTIVES: The aim of the present study was to evaluate the role of
      adenosine and dopamine receptors in the development of rapid tolerance to ethanol
      induced motor incoordination in mice. METHODS: In connection with the rota-rod
      apparatus, the effects of acute administration of the adenosine receptor
      antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX,
      adenosine A1 receptor antagonist) and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo
      {2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, adenosine A2A receptor
      antagonist), together with R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine (SCH23390, dopamine D1 receptor antagonist) and
      sulpiride (dopamine D2 receptor antagonist), alone or in combination with ethanol
      (2.25 g/kg, i.p.), were studied. Twenty-four hours after, all animals were re
      tested on the rota-rod after receiving the same dose of ethanol. RESULTS: The
      repeated administration of ethanol promoted a significant reduction of motor
      impairment on day 2 (i.e. rapid tolerance). This effect was blocked by caffeine
      (3.0-30.0 mg/kg, i.p.), DPCPX (3.0-6.0 mg/kg, i.p.) or SCH23390 (0.01-0.03 mg/kg,
      s.c.), but not with ZM241385 (0.5-1.0 mg/kg, i.p.) or sulpiride (1.0-3.0 mg/kg,
      i.p.). CONCLUSIONS: Our results suggest that the rapid tolerance to ethanol
      induced motor impairment in mice may be modulated by adenosine A1 receptors and
      dopamine D1 receptors.

PMID- 15983798
TI  - Does modafinil activate the locus coeruleus in man? Comparison of modafinil and
      clonidine on arousal and autonomic functions in human volunteers.
AB  - RATIONALE: Modafinil is a wakefulness-promoting drug which is likely to activate
      some wakefulness-promoting and/or inhibit sleep-promoting neurones in the brain.
      The locus coeruleus (LC) is a wakefulness-promoting noradrenergic nucleus whose
      activity can be "switched off" by the alpha2-adrenoceptor agonist clonidine,
      leading to sedative and sympatholytic effects. OBJECTIVE: The aim of the study is
      to compare the effects of single doses of modafinil and clonidine on arousal and
      autonomic functions in human volunteers. METHODS: Sixteen healthy male volunteers
      participated in four experimental sessions (modafinil 200 mg; clonidine 0.2 mg;
      modafinil 200 mg + clonidine 0.2 mg; placebo) at weekly intervals, according to a
      balanced double-blind protocol. Arousal [pupillary "fatigue waves" (PFW),
      critical flicker fusion frequency, self-ratings of alertness] and autonomic
      functions (pupil diameter, pupillary light and darkness reflex responses, blood
      pressure, heart rate, salivation) were recorded. Data were analyzed with ANOVA,
      with multiple comparisons. RESULTS: Clonidine reduced subjective alertness, pupil
      diameter, the initial velocity and amplitude of the darkness reflex response,
      systolic and diastolic blood pressure and salivation, prolonged the recovery time
      of the light reflex response and increased PFW. Modafinil reduced PFW, increased
      pupil diameter and the initial velocity of the darkness reflex response and
      tended to reduce the effect of clonidine on pupil diameter and PFW. Modafinil had
      no effect on non-pupillary autonomic functions. CONCLUSIONS: Clonidine exerted
      sympatholytic and sedative effects, whereas modafinil had sympathomimetic and
      some alerting effects. Modafinil may activate noradrenergic neurones in the LC
      involved in arousal and pupillary control, without affecting extracoerulear
      noradrenergic neurones involved in cardiovascular and salivary regulation.

PMID- 15983799
TI  - Urocortin 1 expression in five pairs of rat lines selectively bred for
      differences in alcohol drinking.
AB  - RATIONALE: There is accumulating evidence that the neuropeptide urocortin 1
      (Ucn1) is involved in alcohol consumption. Thus far, however, most studies have
      been performed in mice. OBJECTIVES: The purpose of the present study was to
      characterize Ucn1 expression in rats selectively bred for either high or low
      alcohol intake. METHODS: Brains from naive male rats of five pairs of
      independently selected lines (iP/iNP, AA/ANA, HARF/LARF, HAD1/LAD1, and
      HAD2/LAD2) were analyzed by immunohistochemistry. RESULTS: Significant
      differences were found between iP/iNP, HARF/LARF, and HAD2/LAD2 in number of Ucn1
      containing cells in the Edinger-Westphal (EW) nucleus (the main source of Ucn1 in
      the brain), whereas no significant differences were found between HAD1/LAD1 and
      AA/ANA. Similarly, significant differences in the optical density of Ucn1
      immunoreactivity in EW were found between iP/iNP, HARF/LARF, and HAD2/LAD2,
      whereas no differences on this measure were found between HAD1/LAD1 and AA/ANA.
      In the lateral septum (LS, the main projection area of Ucn1-containing neurons in
      the rat), significant differences were found only between AA/ANA and HAD2/LAD2;
      however, a meta-analysis indicated that across all five lines, preferring animals
      had a significantly greater number of Ucn1-positive fibers than nonpreferring
      animals. CONCLUSIONS: These results provide evidence that, in rats, Ucn1 may be
      involved in regulation of alcohol intake, and that this regulation may occur
      through the Ucn1 projections to LS.

PMID- 15983800
TI  - Effects of tiagabine in combination with intravenous nicotine in overnight
      abstinent smokers.
AB  - RATIONALE: Preclinical studies suggest that medications enhancing the brain gamma
      amino butyric acid (GABA) system attenuate the rewarding effects of stimulants
      including nicotine. These preclinical studies have not been followed up in
      systematic human studies. OBJECTIVES: This study was conducted to examine the
      effects of a GABAergic medication, tiagabine, on acute physiological and
      subjective effects of intravenous (i.v.) nicotine and on tobacco withdrawal
      symptoms in overnight abstinent smokers. The proposed mechanism of action for
      tiagabine is selective inhibition of GABA transporter type I, which leads to
      increases in synaptic GABA levels. METHODS: Eight male and four female smokers
      participated in a double-blind, placebo-controlled, crossover study. In each of
      three experimental sessions, participants were treated orally with a single 4- or
      8-mg dose of tiagabine or placebo. Two hours following the medication treatment,
      participants received i.v. saline, followed 30 min later by 1.5 mg/70 kg i.v.
      nicotine. RESULTS: Tiagabine treatment did not affect the heart rate or blood
      pressure changes induced by nicotine. There was a significant treatment effect
      for the subjective responses to nicotine, such that tiagabine, compared to
      placebo, attenuated the ratings of "good effects" and "drug liking." Tiagabine
      treatment at 8 mg attenuated the craving for cigarettes and enhanced the
      cognitive performance in the Classical Stoop Tests, compared to placebo or 4 mg
      tiagabine condition. CONCLUSIONS: These results suggest that GABA enhancing
      medication tiagabine may reduce the rewarding effects of nicotine and improve
      cognitive performance in abstinent smokers. The utility of GABA medications for
      smoking cessation needs to be examined further in controlled clinical trials.

PMID- 15983801
TI  - Impairment of specific episodic memory processes by sub-psychotic doses of
      ketamine: the effects of levels of processing at encoding and of the subsequent
      retrieval task.
AB  - RATIONALE: The precise nature of the impact of the N-methyl-D-aspartate
      antagonist, ketamine, upon human episodic memory, has yet to be elucidated fully.
      OBJECTIVES: This study sought to assess the effects of ketamine on the sub
      processes facilitating memory encoding and retrieval. METHODS: We evaluated the
      effects of the drug on a series of memory performance measures depending upon
      whether it was administered at the encoding or retrieval stage and on the nature
      of the encoding task used. Twelve healthy volunteers participated in a double
      blind, placebo-controlled, randomized, within-subjects study. Intravenous
      infusions of placebo, 50 ng/ml ketamine or 100 ng/ml ketamine were administered.
      We investigated the effects of ketamine on three key aspects of episodic memory:
      encoding vs retrieval processes, source memory, and depth of processing. Data
      were analysed using both multinomial modelling and standard measures of item
      discrimination and response bias. RESULTS: Deleterious effects of ketamine on
      episodic memory were primarily attributable to its effects on encoding, rather
      than retrieval processes. Recognition memory was impaired for items encoded at an
      intermediate level of processing, but preserved for shallowly and deeply encoded
      items. Increased source guessing bias was also observed when encoding took place
      under ketamine. CONCLUSIONS: The effects of ketamine upon episodic memory seem,
      therefore, to predominate at encoding. Furthermore, our results are also
      consistent with a specific impairment of encoding processes that result in
      subsequent recollective, as opposed to familiarity-based, retrieval. The observed
      effects are compatible with memory deficits seen in schizophrenia and thus
      provide some support for the ketamine model of the disease.

PMID- 15983802
TI  - Gene cloning and in vivo characterization of a dibenzothiophene dioxygenase from
      Xanthobacter polyaromaticivorans.
AB  - Xanthobacter polyaromaticivorans sp. nov. 127W is a bacterial strain that is
      capable of degrading a wide range of cyclic aromatic compounds such as
      dibenzothiophene, biphenyl, naphthalene, anthracene, and phenanthrene even under
      extremely low oxygen [dissolved oxygen (DO)< or = 0.2 ppm] conditions (Hirano et
      al., Biosci Biotechnol Biochem 68:557-564, 2004). A major protein fraction
      carrying dibenzothiophene degradation activity was purified. Based on its partial
      amino acid sequences, dbdCa gene encoding alpha subunit terminal oxygenase
      (DbdCa) and its flanking region were cloned and sequenced. A phylogenetic
      analysis based on the amino acid sequence demonstrates that DbdCa is a member of
      a terminal oxygenase component of group IV ring-hydroxylating dioxygenases for
      biphenyls and monocyclic aromatic hydrocarbons, rather than group III
      dioxygenases for polycyclic aromatic hydrocarbons. Gene disruption in dbdCa
      abolished almost of the degradation activity against biphenyl, dibenzothiophene,
      and anthracene. The gene disruption also impaired degradation activity of the
      strain under extremely low oxygen conditions (DO< or = 0.2 ppm). These results
      indicate that Dbd from 127W represents a group IV dioxygenase that is functional
      even under extremely low oxygen conditions.

PMID- 15983803
TI  - Proteome response of Escherichia coli fed-batch culture to temperature downshift.
AB  - During fed-batch cultivation of Escherichia coli K-12, the proteomic response to
      a temperature downshift from 37 to 20 degrees C was quantitatively monitored and
      analyzed by using two-dimensional electrophoresis. When the temperature of
      exponentially growing E. coli K-12 culture was downshifted to 20 degrees C, the
      synthesis level of 57 intracellular proteins showed significant changes for a
      prolonged period of time, compared to the fed-batch culture controlled at 37
      degrees C. Thus, these proteins are regarded as important stress proteins
      responsive to cold shock, which were analyzed by using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and identified using the
      E. coli SWISS-2DPAGE database. Most of the identified proteins were shown to be
      involved in energy metabolism, several cellular molecule biosynthetic pathways
      and catabolism, cell processes, flagellar biosynthesis and motility, and protein
      translation and folding. The systematic approach to the monitoring of proteomic
      responses and the detailed analysis results reported in this article would be
      useful in understanding the metabolic adaptation to lowered culture temperature
      and designing efficient fermentation strategies for the production of recombinant
      proteins and metabolites using E. coli strains.

PMID- 15983804
TI  - Effect of red mold rice on antifatigue and exercise-related changes in lipid
      peroxidation in endurance exercise.
AB  - This study evaluated the effect of red mold rice supplementation on antifatigue
      and exercise-related changes in lipid peroxidation of male adult Wistar rats
      through swimming exercise. Thirty 16-week-old rats were studied by dividing them
      into three groups (ten for each group). Other than the control group (CD), the
      other two groups were divided into a high-dose (HD) treatment group (5 g red mold
      rice/kg body weight for the HD group), and a low-dose (LD) group (1 g red mold
      rice/kg body weight for the LD group). Swimming endurance tests were conducted
      after 28 days of red mold rice supplementation, and the result showed that the
      treatment group showed a higher exercise time (CD, 78.0+/-6.4; LD, 104.2+/-9.6;
      and HD, 129.4+/-10.9 min; p<0.05) and a higher blood glucose concentration (CD,
      76.67+/-8.08; LD, 111.34+/-8.50; and HD, 117.67+/-11.06 mg/dl; p<0.05) than the
      CD. Moreover, the blood lactate (CD, 45.00+/-0.90; LD, 31.41+/-1.80; and HD,
      28.89+/-1.62 mg/dl; p<0.05), blood urea nitrogen (CD, 21.87+/-0.75; LD, 20.33+/
      0.83; and HD, 20.53+/-1.09 mg/dl; p<0.05), and hemoglobin (CD, 14.20+/-0.21; LD,
      13.70+/-0.55; and HD, 13.28+/-0.35 g/dl; p<0.05) were also significantly lower
      than those of the CD. Besides, the result suggested that the red mold rice
      supplementation may decrease the contribution of exercise-induced oxidative
      stress and improve the physiological condition of the rats.

PMID- 15983805
TI  - DGGE analysis of 16S rDNA of ammonia-oxidizing bacteria in chemical-biological
      flocculation and chemical coagulation systems.
AB  - Microbial community DNA was extracted from activated sludge samples taken from a
      chemical bioflocculation process and a chemical coagulation process in Shanghai,
      China. 16S rDNA of ammonia-oxidizing bacteria (AOB)was amplified by nested
      polymerase chain reaction and fingerprinted by denaturing gradient gel
      electrophoresis for microbial structure analysis. The Shannon diversity index of
      each sample was determined. The results indicated that the microbial structure of
      AOB in chemical bioflocculation process was comparable at two operational
      conditions. The ammonia-oxidizing bacterial communities were similar in three
      channels of the chemical bioflocculation process and in three serial tanks in the
      chemical coagulation process at the same condition. The diversity of microbial
      structures in the chemical bioflocculation process was higher than in the
      chemical coagulation process, in which the microbial structure was similar to
      that in the influent. Although the microbial study provides insights to the
      nitrification removal, higher microbial diversity of AOB does not necessarily
      mean higher ammonia oxidization. Molecular analysis should be combined with
      chemical assays to optimize operational conditions.

PMID- 15983806
TI  - Metabolic engineering of Aeromonas hydrophila for the enhanced production of
      poly(3-hydroxybutyrate-co-3-hydroxyhexanoate).
AB  - Wild-type Aeromonas hydrophila 4AK4 produced 35-45 wt.% poly(3-hydroxybutyrate-co
      3-hydroxyhexanoate) (PHBHHx) consisting of 10-15 mol% 3-hydroxyhexanoate (3HHx).
      To enhance PHBHHx production, vgb gene encoding Vitreoscilla haemoglobin or fadD
      gene encoding Escherichia coli acyl-CoA synthase was co-expressed with
      polyhydroxyalkanoates (PHA) synthesis-related genes including phbAB from
      Wautersia eutropha and phaPCJ from A. hydrophila. Expression of vgb increased
      PHBHHx content from 46 to 53 wt.% without affecting the polymer monomers
      composition, whereas fadD increased both PHBHHx content from 46 to 64 wt.% and
      its 3HHx fraction from 15 to 24 mol%. Co-expression of vgb or fadD gene with PHA
      synthesis-related genes generally increased PHBHHx content over 60 wt.%. Co
      expression of phbAB with vgb increased PHBHHx content and concentration up to
      about 70 wt.% and 4.0 g l-1, respectively. Fermentor study also showed that in
      the recombinants harboring vgb, CDW, PHBHHx concentration and productivity were
      significantly elevated up to 54 g l-1, 28.5 g l-1 and 0.791 g l-1 h-1,
      respectively, suggesting that vgb could promote PHA synthesis. In this strain,
      lac promoter could be used to constitutively express foreign genes such as phbA
      and phbB encoding beta-ketothiolase and NADPH-dependent acetoacetyl-CoA reductase
      of W. eutropha, respectively, without use of IPTG. The results showed that
      combined expression of different genes was a successful strategy to enhance PHA
      production, which could be useful for strain development to construct other
      recombinant PHA-producing strains.

PMID- 15983807
TI  - Process optimization of constitutive human granulocyte-macrophage colony
      stimulating factor (hGM-CSF) expression in Pichia pastoris fed-batch culture.
AB  - Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) is a
      therapeutically important cytokine that is poorly expressed because of its toxic
      effects on the host cells. Extracellular expression of hGM-CSF was obtained by
      cloning its gene in Pichia pastoris under the constitutive glyceraldehyde-3
      phosphate dehydrogenase (GAP) promoter with an N-terminal alpha peptide sequence
      for its extracellular production. The clones obtained were screened for a hyper
      producer following which media and cultivation conditions were optimized in shake
      flasks. Batch and fed-batch studies were performed in a bioreactor where
      different feed compositions were fed exponentially to obtain high biomass
      concentrations. Feeding of complex media allowed us to maintain a high specific
      growth rate of 0.2 h(-1) for the longest time period, and a final biomass of 98 g
      DCW/l was obtained in 34 h. Product formation was found to be growth associated,
      and the product yield with respect to biomass (Y (P/X)) was approximately 2.5
      mg/g DCW. The above fed-batch strategy allowed us to obtain fairly pure
      glycosylated hGM-CSF at a final product concentration of 250 mg/l in the culture
      supernatant with a high volumetric productivity of 7.35 mg l(-1) h(-1).

PMID- 15983808
TI  - The white-rot fungus Cerrena unicolor strain 137 produces two laccase isoforms
      with different physico-chemical and catalytic properties.
AB  - Cerrena unicolor secreted two laccase isoforms with different characteristics
      during the growth in liquid media. In a synthetic low-nutrient nitrogen glucose
      medium (Kirk medium), high amounts of laccase (4,000 U l(-1)) were produced in
      response to Cu2+. Highest laccase levels (19,000 U l(-1)) were obtained in a
      complex tomato juice medium. The isoforms (Lacc I, Lacc II) were purified to
      homogeneity with an overall yield of 22%. Purification involved ultrafiltration
      and Mono Q separation. Lacc I and II had M (w) of 64 and 57 kDa and pI of 3.6 and
      3.7, respectively. Both isoforms had an absorption maximum at 608 nm but
      different pH optima and thermal stability. Optimum pH ranged from 2.5 to 5.5
      depending on the substrate. The pH optima of Lacc II were always higher than
      those of Lacc I. Both laccases were stable at pH 7 and 10 but rapidly lost
      activity at pH 3. Their temperature optimum was around 60 degrees C, and at 5
      degrees C they still reached 30% of the maximum activity. Lacc II was the more
      thermostable isoform that did not lose any activity during 6 months storage at 4
      degrees C. Kinetic constants (K (m), k (cat)) were determined for 2,2'-azino
      bis(3-ethylthiazoline-6-sulfonate) (ABTS), 2,6-dimethoxyphenol and
      syringaldazine.

PMID- 15983809
TI  - Photoreceptors and visual pigments in the retina of the fully anadromous green
      sturgeon (Acipenser medirostrus) and the potamodromous pallid sturgeon
      (Scaphirhynchus albus).
AB  - Green sturgeon and pallid sturgeon photoreceptors were studied with scanning
      electron microscopy (SEM), microspectrophotometry and, in the case of the green
      sturgeon, retinal whole-mounts. The retinas of both species contain both rods and
      cones: cones comprise between 23% (whole-mount) and 36% (SEM) of the
      photoreceptors. The cone population of both species is dominated by large single
      cones, but a rare small single cone is also present. In both species, most rods
      have long outer segments of large diameter. A rod with a relatively thin outer
      segment is present in the pallid sturgeon retina. Mean cone packing density for
      the entire green sturgeon retina is 4,690+/-891 cones/mm2, with the dorsal retina
      14% more dense than the ventral. There is evidence for a horizontal visual streak
      just above and including the optic disc. Mean rod packing density is 16,006+/
      1,668 rods/mm2 for the entire retina, and fairly uniform throughout. Both species
      have rods with peak absorbance near 540 nm, as well as short-wavelength-sensitive
      cones (green: 464.5+/-0.7 nm; pallid: 439.7+/-3.5 nm); middle-wavelength
      sensitive cones (green: 538.0+/-1.4 nm; pallid: 537.0+/-1.7 nm); and long
      wavelength-sensitive cones (green: 613.9+/-3.0 nm; pallid: 617.8+/-7.6 nm).

PMID- 15983810
TI  - Chronic bilateral common carotid artery occlusion: a model for ocular ischemic
      syndrome in the rat.
AB  - BACKGROUND: Ocular ischemic syndrome is a devastating eye disease caused by
      severe carotid artery stenosis. The reduction of blood flow produced by bilateral
      common carotid artery occlusion (BCCAO) of rats for 7 days induces events related
      to gliosis with no evident histological damage. However, retinal degeneration and
      cellular death occur after 90 days of BCCAO. Our purpose has been to investigate
      the effects of BCCAO for 30 days in the retina of adult rats. METHODS: Adult
      Wistar rats were submitted to BCCAO or sham surgery. Both direct and consensual
      pupillary light reflexes were investigated before and after surgery, everyday for
      the first week and weekly for 30 days. After 1 month, eyes were enucleated and
      embedded in paraffin. The retinal ganglion cell (RGC) density and thickness of
      the internal plexiform (IPL), internal nuclear, outer plexiform, and outer
      nuclear layers were estimated. RESULTS: Four rats of the BCCAO group (50%) lost
      the direct pupillary reflex in both eyes, three rats (37%) lost this reflex in
      one eye, and only one (13%) maintained it in both eyes. RGC density (cells/mm)
      was diminished in the BCCAO group, and a significant decrease was found in the
      total retina and IPL thickness; however, no changes were evident in the other
      layers. BCCAO pupillary-reflex-negative rats presented with a significant
      decrease in total retinal thickness and retinal ganglion cell density compared
      with the sham group. Both BCCAO pupillary-reflex-positive) and -negative rats
      showed a decrease in IPL compared with the sham group. CONCLUSION: This study
      demonstrates that BCCAO for 30 days induces functional and morphological damage
      to the retina with loss of the pupillary reflex and a decrease in IPL thickness
      and RGC number. We suggest that this protocol might be used as a model for ocular
      ischemic syndrome in the rat.

PMID- 15983811
TI  - Risk and prognostic factors of poor visual outcome in Behcet's disease with
      ocular involvement.
AB  - PURPOSE: The purpose of the study was to determine factors correlated with the
      progression of irreversible visual disturbance in Behcet's disease (BD) with
      ocular involvement. METHODS: Forty-seven BD patients with ocular inflammation,
      who presented with the first ocular episode, and who had been followed
      continuously for 5-10 years in our hospital, were studied. Charts were reviewed
      for gender, onset age of uveitis, complete or incomplete type BD, HLA-B51 status,
      final visual acuity at the last remission period, mean number of ocular attacks
      per year, and clinical findings of iridocyclitis with profuse hypopyon, strong
      vitreous opacity blocking the observation of retinal vessels, diffuse retinal
      vasculitis, and exudates with hemorrhage within the retinal vascular arcade.
      RESULTS: Patients with a visual acuity of < or =20/200 and those with >20/200
      differed significantly in the mean number of ocular attacks per year and clinical
      findings of strong vitreous opacity and exudates within the retinal vascular
      arcade, but not with regard to the other factors. In addition, the frequency of
      ocular attacks showed a significant negative correlation with the outcome of
      visual acuity. Logistic regression analysis indicated a significant association
      of an average of more than three ocular attacks per year, strong vitreous
      opacity, and exudates within the retinal vascular arcade with poor visual
      outcome. CONCLUSIONS: This study indicates that more than three ocular attacks
      per year, strong vitreous opacity, and exudates within the retinal vascular
      arcade are the risk and prognostic factors for a poor outcome of visual acuity in
      BD patients.

PMID- 15983812
TI  - Induction of nestin, Ki-67, and cyclin D1 expression in Muller cells after laser
      injury in adult rat retina.
AB  - PURPOSE: The purpose was to examine the expression of nestin, Ki-67, and cyclin
      D1 in Muller cells after laser injury in adult rat retina. METHODS: The right
      eyes of adult Brown Norway rats were treated with laser photocoagulation. The
      eyes were removed 3, 7, and 14 days after laser treatment. The retinas were
      investigated immunocytochemically by confocal microscopy. Agarose-embedded
      sections were immunostained with antibodies to nestin, vimentin, glial fibrillary
      acidic protein (GFAP), glutamate-aspartate transporter (GLAST), rhodopsin, Ki-67,
      and cyclin D1. Cell death was examined using terminal deoxynucleotidyl
      transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL)
      assay on agarose sections. RESULTS: Nestin expression was induced in Muller cells
      following laser injury. In addition, Ki-67 and cyclin D1 expression was found in
      the nuclei of Muller cells after the treatment. TUNEL assay demonstrated that
      Muller cells were not labeled; hence these cells were not apoptotic. CONCLUSIONS:
      These results suggest that dedifferentiation and proliferation of Muller cells
      can be induced by laser injury in adult rat retina.

PMID- 15983813
TI  - Combined use of perfluorohexyloctane and silicone oil as intraocular tamponade:
      an in vitro study.
AB  - BACKGROUND: Double filling (DF) with perfluorohexyloctane (F6H8) and silicone oil
      (SIL) has been recently proposed and tested clinically as a means to improve the
      tamponade properties of single components. This in vitro study investigated (1)
      the kinetics of the mixing process of F6H8 with SIL (1,000 mPa s) and (2) the
      contact and emulsification behaviour of DF as compared with pure liquids, with
      the aim of assessing the tamponade efficiency and its evolution with time.
      METHODS: (1) The velocity of the mixing process for F6H8+SIL was estimated by
      monitoring the position of the interphase in a rectangular cell kept at constant
      temperature. (2) The surface contact and the tendency to emulsification of DF and
      of SIL and F6H8 were visually examined by using a Perspex eye model. RESULTS: (1)
      The mixing process for F6H8+SIL is slow. In the absence of stirring, equilibrium
      is reached no earlier than 1 month at 37 degrees C. (2) F6H8 was found to show
      close contact with the eye model and dispersion into droplets; SIL showed poor
      contact with the cell surface and no dispersion; DF exhibited poor contact with
      the superior cell surface and little evidence of dispersion. CONCLUSIONS: F6H8
      dissolves slowly in SIL and equilibrium is only reached after 1 month. The final
      ratio of the DF phases differs from the initial ratio. An initial F6H8/SIL ratio
      of 70%:30% vol results in 25% vol of pure F6H8 (density, 1.33 g/cm(3)) and 75%
      vol of a solution containing F6H8, viz. 60% vol F6H8 in SIL (density 1.17
      g/cm(3)). Because of its density and contact properties, the investigated DF has
      a tamponade effectiveness better than that of SIL on the inferior retina.
      Compared with using F6H8 alone, DF reduces emulsification.

PMID- 15983814
TI  - Effectiveness of sodium hyaluronate eyedrops in the treatment of dry eye.
AB  - BACKGROUND: Dry eye is a common condition, affecting approximately 10-20% of the
      adult population. Artificial tears are often effective in relieving symptoms in
      mild and moderate dry eye by replenishing deficient tear volume. Sodium
      hyaluronate has been proposed as a component in artificial tears, due to its
      viscoelastic rheology. This paper reports on a study carried out to assess the
      efficacy of two recently developed eyedrops containing 0.1% and 0.3% sodium
      hyaluronate (SH) in the treatment of moderate dry eye. METHODS: Thirteen subjects
      were recruited with moderate dry eye. Forty microlitres of 0.1% SH, 0.3% SH, or
      0.9% saline were instilled in both eyes, and the subjects' symptom intensity and
      non-invasive break-up time (NIBUT) were measured at 5, 15, 30, 45, and 60 min,
      and then hourly, until 6 h after drop instillation. This was repeated twice
      following an interval of 7(+/-1) days, but with a different treatment so that at
      the end of the final visit each subject had trialled all products. Drop
      allocation was randomized and double-masked. RESULTS: Both symptoms and NIBUT
      improved with all treatments. These changes were of a larger magnitude and longer
      duration with the SH containing eyedrops than with saline. SH of 0.3% tended to
      perform better than 0.1% SH and achieved statistical significance (P=0.04) for
      NIBUT when considered over the whole 6-h study period. CONCLUSIONS: Sodium
      hyaluronate of 0.1% and 0.3% reduces symptoms of ocular irritation and lengthens
      NIBUT in subjects with moderate dry eye more effectively than saline, in terms of
      peak effect and duration of action.

PMID- 15983815
TI  - mfERG in normal and lesioned rabbit retina.
AB  - BACKGROUND: To evaluate and describe the cone function in the normal and lesioned
      rabbit retina using the multifocal electroretinogram (mfERG). METHODS: Twelve
      animals underwent a two-port vitrectomy with subsequent retinectomy in one eye.
      The area of removed retina was located in the nasal part of the visual streak,
      and measured approximately 1-2 disc diameters. Both eyes were investigated with
      mfERG preoperatively and up to 13 weeks postoperatively. A Burian-Allen bipolar
      contact lens with built-in infrared emitters was used to visualize the retina
      during the recordings. The averages of the trace array amplitudes in the lower
      nasal and temporal quadrants were calculated and statistically analyzed at the
      different time intervals. All eyes were examined histologically with hematoxylin
      and eosin staining. RESULTS: The retina could be visualized during the mfERG
      examinations. Postoperatively, up to 3 weeks, amplitudes were reduced over the
      entire stimulated area in retinectomized eyes (2.20 microV+/-1.22 SD) as compared
      with preoperative examinations (3.40 microV+/-1.00 SD). After 7 weeks the
      amplitudes in the quadrant including the retinectomized area remained low (2.62
      microV+/-1.02 SD), whereas they were higher than at earlier postoperative
      examinations in the lower unlesioned temporal quadrant (3.56 microV+/-0.71 SD)
      with a statistical difference between the quadrants. At 13 weeks this was even
      more pronounced. In unoperated eyes, the area corresponding to the visual streak
      displayed significantly higher amplitudes than the area superior to the
      myelinated streak, corresponding well to the cone distribution. High amplitudes
      were also detected in the area of the myelinated nerve fibers and optic nerve
      head, most likely as a result of scattering light. In histological sections, the
      retinectomized area had a diameter of 1-3 mm. CONCLUSIONS: This study shows that
      the mfERG technique can be used as a tool in experimental retinal research
      involving the rabbit eye, where retinal lesions down to at least 1 mm can be
      detected. One difficulty involves scattering light emanating from the relatively
      large optic disc and the myelinated nerve fibers, which makes the use of a mfERG
      system, in which the fundus can be visualized during stimulation, mandatory.

PMID- 15983816
TI  - Optical coherence tomography study of tilted optic disk associated with macular
      detachment.
AB  - PURPOSE: To describe the macular findings by optical coherence tomography in both
      eyes of a patient with tilted optic disk and visual decrease. METHODS: A 35-year
      old woman with bilateral tilted optic disk and serous macular detachment was
      examined by slit-lamp biomicroscopy, fluorescein angiography, indocyanine green
      angiography and optical coherence tomography (OCT). RESULTS: Fluorescein
      angiography demonstrated staining of the temporal rim of the staphyloma adjacent
      to the optic disk and hyperfluorescence of the diffuse pigmentary changes in the
      papillomacular area. Leakage points and serous macular detachment were not
      observed. The existing neurosensory detachment at the fovea became evident only
      by OCT. CONCLUSIONS: The existence of subretinal fluid, which became evident only
      by OCT, supports the view that OCT could further contribute to the study of the
      asymptomatic pigmentary lesions of the macula that are present in 11% of eyes
      with tilted optic disk. The reason for the localized macular detachment remains
      unclear. Dysfunction of the retinal pigment epithelium (RPE) or leakage of the
      optic disk staphyloma rim could possibly explain the cause of fluid accumulation
      in the macula.

PMID- 15983817
TI  - A pilot study on the use of silicone oil-RMN3 as heavier-than-water endotamponade
      agent.
AB  - AIMS: This work was conducted to report an interventional non-comparative pilot
      study using Oxane HD, a mixture of ultra-purified silicone oil and RMN3, a
      partially fluorinated olefin, as heavier-than-water internal tamponade. METHODS:
      Twenty-eight consecutive patients were recruited for this study. Indications
      included recurrent retinal detachment (RD) with proliferative vitreoretinopathy
      (PVR) (stage > or =C2) arising from inferior or posterior tears, recurrences
      after vitreoretinal surgery, penetrating trauma and combined rhegmatogenous and
      choroidal detachment. The patients underwent a pars plana vitrectomy, membrane
      peeling, and Oxane HD was used as long-term internal tamponade. RESULTS: Oxane
      was removed after 88 days (range 45-96 days) and exchanged with BSS in five eyes,
      long-acting gas in 14 eyes and with silicone oil in nine eyes. Retinal
      reattachment was achieved in 15 eyes. The overall anatomical success rate
      obtained using Oxane HD was 53.5%. In 15 patients with previous marked scleral
      buckling, the success rate was 26%: in nine patients recurrent RD occurred in the
      inferior sector, in five patients new tears were detected in the lower sectors;
      membrane formation was observed in 15 eyes. In 13 patients without marked scleral
      indent, the success rate was 84.6%. There was no evidence of dispersion and
      excessive inflammation. CONCLUSION: Oxane HD may be a useful tool in complicated
      RD with large inferior breaks, inferior PVR or combined rhegmatogenous, and
      choroidal detachment without marked scleral buckling, which put the eye profile
      out of shape, led to a higher failure rate and reduced the tamponading
      effectiveness of Oxane HD.

PMID- 15983818
TI  - Adenocarcinoma arising from congenital hypertrophy of the retinal pigment
      epithelium.
AB  - BACKGROUND: Adenocarcinoma of the retinal pigment epithelium (RPE) is a rare
      primary malignant intraocular neoplasm. We report a histopathologically confirmed
      case of adenocarcinoma of the retinal pigment epithelium arising from congenital
      hypertrophy of the retinal pigment epithelium (CHRPE). METHODS: The clinical
      features, surgical management, and histopathological features of a melanotic
      tumor arising from CHRPE are presented. The tumor was excised by transcleral
      resection. RESULTS: Histopathological and immunohistochemical study of the tumor
      showed it to be an adenocarcinoma of the RPE. CONCLUSIONS: Adenocarcinoma of the
      RPE arising from CHRPE is extremely rare. Such a tumor can resemble a choroidal
      melanoma. In spite of the rarity of this association, periodic monitoring of
      CHRPE for development of a nodular tumor of the RPE is probably warranted.

PMID- 15983819
TI  - Composite follicular lymphoma and nodular lymphocyte predominance Hodgkin's
      disease.

PMID- 15983820
TI  - Frequency and character of alternative somatic recombination fates of paralogous
      genes during T-DNA integration.
AB  - A synthetic RBCSB gene cluster was transformed into Arabidopsis in order to
      simultaneously evaluate the frequency and character of somatic illegitimate
      recombination, homologous recombination, and targeted gene replacement events
      associated with T-DNA-mediated transformation. The most frequent type of
      recombination event observed was illegitimate integration of the T-DNA without
      activation of the silent DeltaRBCS1B: LUC transgene. Sixteen luc(+) (firefly
      luciferase positive) T1 plants were isolated. Six of these were due to
      illegitimate recombination events resulting in a gene trapping effect. Nine
      resulted from homologous recombination between paralogous RBCSB sequences
      associated with T-DNA integration. The frequency of somatic homologous
      recombination associated with T-DNA integration was almost 200 times higher than
      previously reported rates of meiotic homologous recombination with the same
      genes. The distribution of (somatic homologous) recombination resolution sites
      generally fits a fractional interval length model. However, a small region
      adjacent to an indel showed a significant over-representation of resolution
      sites, suggesting that DNA mismatch recognition may also play an important role
      in the positioning of somatic resolution sites. The frequency of somatic
      resolution within exon-2 was significantly different from that previously
      observed during meiotic recombination.

PMID- 15983821
TI  - [Free and pedicled muscle transfer as a therapy option in urological surgery].
AB  - Various demands of reconstruction define restoration technique. The basic
      principle involves optimal anatomical and functional reconstruction with
      concurrent minimal donor-site morbidity. Dependent on the aetiology of the
      defect, there are various reconstructive possibilities available for obtaining an
      optimal result. An immediate single stage reconstruction, with the best possible
      result for the individual patient as the primary consideration, can be carried
      out by interdisciplinary teams. In this overview, the most common indications and
      principles of flap choice are presented in relation to the reconstructive
      requirements necessary for early rehabilitation of the patient or the earlier
      start of necessary adjuvant therapy.

PMID- 15983822
TI  - Information deficits in the summary of product characteristics preclude an
      optimal management of drug interactions: a comparison with evidence from the
      literature.
AB  - OBJECTIVE: To compare comprehensiveness and accuracy of drug interaction
      information in the German summary of product characteristics (SPC) with current
      evidence from the literature and to evaluate the SPC's usefulness with respect to
      management of drug interactions. METHODS: Information on clinically relevant drug
      interactions was compared between the SPC and three standard information sources
      on drug interactions (DRUGDEX, Hansten/Horn's Drug Interactions Analysis and
      Management, Stockley's Drug Interactions) according to five consecutive criteria
      (inclusion, appropriateness of class labelling, effect description, management
      recommendation, explicit dose adjustment). Using medication data of an outpatient
      population (n=4,949), we determined what percentage of insufficiently
      characterized combinations indeed occurred in outpatients treated with
      combination drug therapy. RESULTS: Only for 33% (192/579) of the evaluated
      combinations did SPCs provide drug interaction information equivalent to the
      evidence from the published literature. Of the clinically relevant drug
      interactions, 16% were completely missing and 51% were insufficiently
      characterized compared with standard sources. Explicit management recommendations
      were either missing or differed from standard sources in 18% of the evaluated
      pairs of compounds. Of these missing or insufficiently characterized
      combinations, 12% (47/387) were indeed prescribed to outpatients. Those drug
      combinations for which the interaction potential was not mentioned in the SPC
      were received by 0.6% (32/4,949) of patients, and 4% (192/4,949) of patients
      received combinations that had insufficiently characterized drug interactions.
      CONCLUSIONS: If physicians only rely on SPC information for drug interactions,
      adverse events due to lacking management recommendations may occur. To meet the
      SPCs claim of being the basis of information for health professionals on how to
      use medicinal products safely and effectively, information on drug interactions
      should be thoroughly up-dated and expanded.

PMID- 15983823
TI  - Effects of orange juice on the pharmacokinetics of atenolol.
AB  - OBJECTIVE: Fruit juices can significantly change the pharmacokinetics of several
      drugs. Our objective was to investigate the effect of orange juice on the
      pharmacokinetics of the beta-blocking agent atenolol. METHODS: In a randomized
      cross-over study with two phases and a washout of 2 weeks, ten healthy volunteers
      took either 200 ml orange juice or water thrice daily for 3 days and twice on the
      fourth day. On the morning of day 3, each subject ingested 50 mg atenolol with an
      additional amount of either 200 ml orange juice or water. The plasma
      concentrations of atenolol and the cumulative excretion of atenolol into urine
      were measured up to 33 h after its dosing. Systolic and diastolic blood pressures
      and heart rate were recorded in a sitting position before the intake of atenolol
      and 2, 4, 6, and 10 h after. RESULTS: Orange juice decreased the mean peak plasma
      concentration (C(max)) of atenolol by 49% (range 16-59%, P<0.01), and the mean
      area under the plasma atenolol concentration-time curve (AUC(0-33 h)) by 40%
      (range 25-55%, P<0.01). The time of the peak concentration (t(max)) and the
      elimination half-life (t(1/2)) of atenolol remained unchanged by orange juice.
      The amount of atenolol excreted into urine was decreased by 38% (range 17-60%,
      P<0.01), but the renal clearance remained unaltered. The average heart rate was
      slightly higher during the orange juice+atenolol phase than during the
      water+atenolol phase. CONCLUSIONS: Orange juice moderately interferes with the
      gastrointestinal absorption of atenolol. This food-drug interaction can be of
      clinical significance.

PMID- 15983824
TI  - Cardiovascular drug utilisation and socio-economic inequalities in 20 districts
      of the Czech Republic.
AB  - OBJECTIVE: To analyse whether there exists a socio-economic gradient in
      utilisation of cardiovascular drugs at the district level in the Czech Republic.
      METHODS: The aggregated data on drug utilisation during the period 1997-2000,
      expressed in defined daily doses per 1000 inhabitants per day, were obtained from
      the General Health Insurance Company. Socio-economic characteristics of the
      districts in year 2000 (percentage of university-educated inhabitants, percentage
      of single-member households, number of ambulatory physicians per 10,000
      inhabitants, unemployment rate and mean monthly income) were used as single
      unadjusted predictor variables. Partial correlation controlling for age in
      districts was used to analyse the relationship of cardiovascular disease (CVD)
      drug utilisation and several socio-economic variables. RESULTS: There were
      considerable differences in the utilisation of CVD drugs within the districts
      studied. Significantly higher utilisation of dihydropyridine Ca-channel blockers
      and statins was found in the districts with a higher percentage of university
      educated inhabitants and more ambulatory physicians. CVD drug utilisation
      (nitrates, fibrates, selective beta-blockers, verapamil and diltiazem and
      statins) correlated significantly with the percentage of single-member
      households. The five socio-economic variables explained more than 60% of the
      variability in use of dihydropyridine Ca-channel blockers, verapamil and
      diltiazem, ACE inhibitors and statins. CONCLUSION: There exists a significant
      gradient in the utilisation of mainly newer CVD drug groups within districts of
      the Czech Republic that can be, at least partly, explained by social
      characteristics of the districts.

PMID- 15983825
TI  - Scientific drug information in newspapers: sensationalism and low quality. The
      example of therapeutic use of cannabinoids.
AB  - OBJECTIVE: We aimed to analyse the quality of newspaper articles (NAs) concerning
      the therapeutic use of cannabis published in Spanish newspapers. METHODS: A
      preliminary questionnaire of the Index of Scientific Quality was used [scores
      ranged from 0 (no misleading) to 14 (misinformation in each item)]. RESULTS: Of
      the 29 NAs analysed, 16 (55.2%) were scored as 4 or lower, and 6 (20.7%) scored 7
      or higher. Up to 23 NAs (79.3%) did not manage the knowledge related to
      cannabinoids; 20 (69%) gave a sensationalist message; 11 (37.9%) were able to
      wrongly influence clinical decision taking; and 8 (27.6%) misled medical
      concepts. CONCLUSION: The leading medical journals could play an especially
      relevant role while preparing their press releases if they specify study
      limitations and context.

PMID- 15983827
TI  - Ribosome-lamella complex in aggressive solitary fibrous tumour of the meninges.

PMID- 15983826
TI  - Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin.
AB  - OBJECTIVE: To examine the effect of aprepitant on the pharmacokinetics and
      pharmacodynamics of warfarin. Aprepitant is a neurokinin-1 (NK1)-receptor
      antagonist developed as an antiemetic for chemotherapy-induced nausea and
      vomiting. METHODS: This was a double-blind, placebo-controlled, randomized, two
      period, parallel-group study. During period 1, warfarin was individually titrated
      to a stable prothrombin time (expressed as international normalized ratio, INR)
      from 1.3 to 1.8. Subsequently, the daily warfarin dose remained fixed for 10-12
      days. During period 2, the warfarin dose was continued for 8 days, and on days 1
      3 administered concomitantly with aprepitant (125 mg on day 1, and 80 mg on days
      2 and 3) or placebo. At baseline (day -1 of period 2) and on day 3, warfarin
      pharmacokinetics was investigated. INR was monitored daily. During period 2,
      warfarin trough concentrations were determined daily. RESULTS: The study was
      completed by 22 healthy volunteers (20 men, 2 women). On day 3, steady-state
      pharmacokinetics of warfarin enantiomers after aprepitant did not change, as
      assessed by warfarin AUC(0-24 h) and C(max). However, compared with placebo,
      trough S(-) warfarin concentrations decreased on days 5-8 (maximum decrease 34%
      on day 8, P<0.01). The INR decreased after aprepitant with a mean maximum
      decrease on day 8 of 11% versus placebo (P=0.011). CONCLUSION: These data are
      consistent with a significant induction of CYP2C9 metabolism of S(-) warfarin by
      aprepitant. Subsequently, in patients on chronic warfarin therapy, the clotting
      status should be monitored closely during the 2-week period, particularly at 7-10
      days, following initiation of the 3-day regimen of aprepitant with each
      chemotherapy cycle.

PMID- 15983828
TI  - Myostatin is increased and complexes with amyloid-beta within sporadic inclusion
      body myositis muscle fibers.
AB  - Myostatin is a negative regulator of muscle mass and strength. Sporadic inclusion
      body myositis (s-IBM) is the most common degenerative muscle disease of older
      persons and is characterized by pronounced muscle wasting. s-IBM is of unknown
      etiology and pathogenesis, and it lacks definitive treatment. We have now
      demonstrated in samples from 12 s-IBM biopsies that: (1) by light and electron
      microscopic immunocytochemistry, myostatin/myostatin precursor is accumulated
      within muscle fibers and co-localized with amyloid-beta (Abeta); (2) by
      immunoblots, both myostatin and myostatin precursor are increased; and (3) by
      immunoprecipitation, myostatin precursor complexes with Abeta. Our study suggests
      that myostatin/myostatin precursor, either alone, or bound to Abeta, may play a
      novel role in the pathogenesis of s-IBM.

PMID- 15983829
TI  - Expression of tubulin beta II in neuroepithelial tumors: reflection of
      architectural changes in the developing human brain.
AB  - Tubulin beta II (Tub-II) is widely distributed in the developing neuronal axons
      and dendrites. Recent studies have demonstrated that Tub-II is also important in
      the early development of the human brain, and Tub-II represents a marker for
      progenitor and neural stem cells. To elucidate the correlation between the
      developing brain and neuroepithelial tumors (NETs), the present study assessed
      Tub-II expression by NETs and normal brain tissue using immunohistochemical and
      immunoblot analyses. In the gliomas, decreased numbers and staining intensities
      of Tub-II-positive cells tended to be associated with increased differentiation.
      Conversely, neuronal neoplasms displayed high percentages and strong staining
      intensities among the Tub-II-positive cells, irrespective of differentiation. In
      neuronal neoplasms and neoplasms with neuronal differentiation, Tub-II staining
      was far more intense and more homogeneous than Tub-II staining in gliomas. These
      results indicate that the expression of Tub-II in NETs may reflect architectural
      changes in the developing brain and may support the hypothesis that
      neuroepithelial tumors originate from glioneuronal progenitor cells capable of
      generating astrocytic, and neuronal cell types.

PMID- 15983830
TI  - Redox system expression in the motor neurons in amyotrophic lateral sclerosis
      (ALS): immunohistochemical studies on sporadic ALS, superoxide dismutase 1 (SOD1)
      mutated familial ALS, and SOD1-mutated ALS animal models.
AB  - Peroxiredoxin-ll (Prxll) and glutathione peroxidase-l (GPxl) are regulators of
      the redox system that is one of the most crucial supporting systems in neurons.
      This system is an antioxidant enzyme defense system and is synchronously linked
      to other important cell supporting systems. To clarify the common self-survival
      mechanism of the residual motor neurons affected by amyotrophic lateral sclerosis
      (ALS), we examined motor neurons from 40 patients with sporadic ALS (SALS) and 5
      patients with superoxide dismutase 1 (SOD1)-mutated familial ALS (FALS) from two
      different families (frame-shift 126 mutation and A4 V) as well as four different
      strains of the SOD1-mutated ALS models (H46R/G93A rats and G1H/G1L-G93A mice). We
      investigated the immunohistochemical expression of Prxll/GPxl in motor neurons
      from the viewpoint of the redox system. In normal subjects, Prxll/GPxl
      immunoreactivity in the anterior horns of the normal spinal cords of humans, rats
      and mice was primarily identified in the neurons: cytoplasmic staining was
      observed in almost all of the motor neurons. Histologically, the number of spinal
      motor neurons in ALS decreased with disease progression. Immunohistochemically,
      the number of neurons negative for Prxll/GPxl increased with ALS disease
      progression. Some residual motor neurons coexpressing Prxll/GPxl were, however,
      observed throughout the clinical courses in some cases of SALS patients, SOD1
      mutated FALS patients, and ALS animal models. In particular, motor neurons
      overexpressing Prxll/GPxl, i.e., neurons showing redox system up-regulation, were
      commonly evident during the clinical courses in ALS. For patients with SALS,
      motor neurons overexpressing Prxll/GPxl were present mainly within approximately
      3 years after disease onset, and these overexpressing neurons thereafter
      decreased in number dramatically as the disease progressed. For SOD1-mutated FALS
      patients, like in SALS patients, certain residual motor neurons without
      inclusions also overexpressed Prxll/GPxl in the short-term-surviving FALS
      patients. In the ALS animal models, as in the human diseases, certain residual
      motor neurons showed overexpression of Prxll/GPxl during their clinical courses.
      At the terminal stage of ALS, however, a disruption of this common Prxll/GPxl
      overexpression mechanism in neurons was observed. These findings lead us to the
      conclusion that the residual ALS neurons showing redox system up-regulation would
      be less susceptible to ALS stress and protect themselves from ALS neuronal death,
      whereas the breakdown of this redox system at the advanced disease stage
      accelerates neuronal degeneration and/or the process of neuronal death.

PMID- 15983831
TI  - Do mitochondria regulate the heat-shock response in Saccharomyces cerevisiae?
AB  - A mild heat shock induces the synthesis of heat-shock proteins (hsps), which
      protect cells from damage during more extreme heat exposure. The nature of the
      signals that induce transcription of heat shock-regulated genes remains
      conjectural. In this work we studied the role of mitochondria in regulating hsps
      synthesis in Saccharomyces cerevisiae. The results obtained clearly indicate that
      a mild heat shock elicits a hyperpolarization of the inner mitochondrial membrane
      and such an event is one of several signals triggering the chain of reactions
      that activates the expression of the HSP104 gene and probably the expression of
      other heat shock-regulated genes in S. cerevisiae. The uncouplers or
      mitochondrial inhibitors which are capable of dissipating the potential on the
      inner mitochondrial membrane under particular experimental conditions prevent the
      synthesis of Hsp104 induced by mild heat shock and thus inhibit the development
      of induced thermotolerance. It is suggested that cAMP-dependent protein kinase A
      is participating in the mitochondrial regulation of nuclear genes.

PMID- 15983832
TI  - Mutant meiotic chromosome core components in mice can cause apparent sexual
      dimorphic endpoints at prophase or X-Y defective male-specific sterility.
AB  - Genetic modifications causing germ cell death during meiotic prophase in the
      mouse frequently have sexually dimorphic phenotypes where oocytes reach more
      advanced stages than spermatocytes. To determine to what extent these dimorphisms
      are due to differences in male versus female meiotic prophase development, we
      compared meiotic chromosome events in the two sexes in both wild-type and mutant
      mice. We report the abundance and time course of appearance of structural and
      recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days
      post coitus show rapid, synchronous meiotic prophase development compared with
      the continuous spermatocyte development in adult testis. Consequently, a genetic
      defect requiring 2-3 days from the onset of prophase to reach arrest registers
      pachytene as the developmental endpoint in oocytes. Pachytene spermatocytes, on
      the other hand, which normally accumulate during days 4-10 after the onset of
      prophase, will be rare, giving the appearance of an earlier endpoint than in
      oocytes. We conclude that these different logistics create apparent sexually
      dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic
      prophase of mice with genetic modifications of meiotic chromosome core components
      that cause male but not female sterility. The correlations between male sterility
      and alterations in the organization of the sex chromosome cores and X-Y chromatin
      may indicate that impaired signals from the XY domain (XY chromosome cores,
      chromatin, dense body and sex body) may interfere with the progression of the
      spermatocyte through prophase. Oocytes, in the absence of the X-Y pair, do not
      suffer such defects.

PMID- 15983835
TI  - [Health telematics, Part 1].

PMID- 15983834
TI  - Distribution of general (PGP 9.5) and sensory (substance P/CGRP) innervations in
      the human patellar tendon.
AB  - There is no information on the pattern of blood vessel innervation, and in
      principle no information on innervation in general, in the human patellar tendon.
      In the present study, biopsies from the proximal part of normal and pain-free
      patellar tendons (11 men, mean age 33 years) were examined. The specimens were
      evaluated by using antibodies against the general nerve marker protein gene
      product 9.5 (PGP 9.5) and the sensory neuropeptides substance P (SP) and
      calcitonin gene-related peptide (CGRP), and immunohistochemistry. It was observed
      that the arteries, and to some extent the small vessels, in the loose
      paratendinous connective tissue were supplied with PGP 9.5- as well as SP- and
      CGRP-innervations. There was a marked PGP 9.5-like immunoreaction (LI), and to
      some extent also SP- and CGRP-LI, in the large nerve fascicles in this tissue. In
      the tendon tissue proper, PGP 9.5-LI was detected in nerve fibers located in the
      vicinity of some of the blood vessels and in thin nerve fascicles. There was a
      low degree of SP- and CGRP-innervation in the tendon tissue proper. The
      observations give a morphologic correlate for the occurrence of nerve-mediated
      effects in the patellar tendon. Particularly it seems as if there is a marked
      nerve-mediated regulation of the blood vessels supplying the tendon, at the level
      where they course in the loose paratendinous connective tissue.

PMID- 15983833
TI  - Role of neuroendoscopy in the management of patients with tuberculous meningitis
      hydrocephalus.
AB  - The role of neuroendoscopy in patients of tuberculous meningitis with
      hydrocephalus (TBMH) is not yet established. We present details of endoscopic
      morphology, and analyze outcome of Neuroendoscopy performed in 28 patients (15
      males and 13 females, average age 23 years) of TBMH in last 2.5 years. Endoscopic
      procedures performed included endoscopic third ventriculostomy (ETV) alone
      (n=19), ETV with monroplasty (n=2), and septostomy (n=2), ETV with
      decompression/biopsy of tuberculoma (n=2) and with abscess drainage (n=1).
      Outcome was assessed on the basis of clinico-radiological improvement, need for
      external shunt and complications. Outcome was satisfactory in 14 (50%),
      acceptable in five (18%) and unsatisfactory in nine (32%) patients. Overall, 19
      (68%) patients benefited from endoscopic intervention. Cerebrospinal fluid (CSF)
      leak (n=2) and per-operative bleeding (n=1) were the only complications
      encountered. Endoscopy appears to be helpful in a considerable number of patients
      with TBMH, and should be considered as the first surgical option for CSF
      diversion surgery in these patients. External shunt should be reserved for those
      who fail the endoscopic CSF diversion.

PMID- 15983836
TI  - [Political aspects and aims of telematics].
AB  - Germany has a health care system that uses sophisticated technologies. On the
      other hand, with respect to the most important human asset--good health-
      duplication of work, media discontinuity, and incompatible documentations
      persist. The sector-oriented service structures and pillars of our health-care
      system are also reflect ed in the area of informatics and communication
      technologies. In the German health care system every institution in itself is an
      isolated solution, partially in line with the latest scientific research, but
      singular. As a rule, the limits of information technology are reached where the
      economic and business capacities of one's own institution are exhausted. So the
      essential advantage of telematics, which is in particular the use of synergistic
      benefits, is given away. Therefore, both the infrastructural conditions for the
      use of telematics have to be improved and also important key applications such as
      the electronic prescription have to be encouraged. By introducing the new
      electronic health card, the nation wide use of health telematics in Germany can
      be promoted. The activities of the Federal Government and the legislation
      initiated within the scope of the Act on the Modernization of the Statutory
      Health Insurance serve to expedite these improvements. The extension of the
      current health insurance card to an electronic health card is the task of the
      central associations of self-administration. They are also obligated to fulfill
      the agreement on the infrastructure necessary for the electronic health card.

PMID- 15983837
TI  - [Telematics in the health system and data protection].
AB  - In the health system, telematics are to be used for the benefit of patients and
      to make it possible for them to receive better medical care. Telematics must be
      employed in accordance with the guidelines of data protection and this means in
      particular that the patient must remain the master of his data. Therefore, he
      must be able to decide in which situation and to whom he wants to reveal his
      medical data. For this reason, the exact implementation of the introduction of
      the electronic medical smart card envisaged by the law requires detailed access
      authorisations and limitations, which must be reinforced by ample technical
      security measures. These measures must be transmitted to the patients through co
      operation of doctors and health insurance companies in such a transparent way
      that they recognise the advantages of the new technology. The higher the
      acceptance is on the patients' side, the more they will be willing to participate
      voluntarily in telematic projects.

PMID- 15983838
TI  - [Legal aspects of health telematics].
AB  - Specific legal issues arise from the distance of the participants in health
      telematics. Substandard care not meeting the state of the art can yield
      malpractice litigation, especially if a diagnosis or therapy conveyed via
      telematics proves to be deficient. On the other hand, communication deficiencies
      may bring about a reversal of the burden of proof. If the patient's damage can
      not be attributed to the responsible person due to the division of labour, a
      joint liability is likely to be adjudicated. A specific legal risk analysis is
      required as a basis for a risk-adequate design of any application in health
      telematics.

PMID- 15983839
TI  - [Economic aspects of health telematics].
AB  - The economic aspects of the health telematics must be considered from two points
      of view. The administrative applications are suitable as start-applications,
      because their data structures and processes are well known, and the calculation
      of the individual monetary effects have a solid empirical basis. However, only
      the medical applications will exhaust the real potential of health telematics and
      only these applications will justify the political and financial effort involved.

PMID- 15983840
TI  - [The telematic platform trial concept. An attempt at definition and
      clarification].
AB  - A telematic platform provides a comprehensive infrastructure for communication of
      health data among several participants in the health care system. The planned
      introduction of the electronic health card and accompanying measures in 2006 is
      the first step towards the realisation of a telematic platform. The course for
      further development of the platform will be set during this important initial
      phase.

PMID- 15983841
TI  - [Health telematics projects in the perspective of the German federal states].
AB  - Starting in autumn 2005 with pilot projects, the new German electronic health
      card (EHC) and electronic health professional cards (HPC) will be implemented in
      the German health system. These cards are constituents of the full coverage
      networking of more than 120,000 doctor's practices, 22,000 pharmacies, 2,200
      hospitals and 300 health insurance companies. The functions of the EHC, for
      example electronic prescriptions, the digital medication recording and the
      European emergency database, need both the interactions with the HPCs and with a
      complex network of IT systems and telecommunication services, i. e. with a
      comprehensive health telematics infrastructure. Model regions for the
      construction of a telematics infrastructure have been established in numerous
      federal states, e. g. Baden- Wurttemberg, Bavaria, Bremen, Lower Saxony, North
      Rhine-Westphalia, Rhineland-Palatinate, Saxony and Schleswig-Holstein, and also
      recently in Mecklenburg-Vorpommern and Brandenburg. These model regions are
      designed in a way that allows smooth integration of the specifications of the so
      called solution architecture of the EHC and also of electronic HPCs as soon as
      these are available. The implementation of first pilot trials in the model
      regions, each with 10,000 insured, is planned for the second half of 2005. A
      project task force was founded by a group from the German federal states in
      December 2004. The objective of these implementations is to establish a fully
      networked health system providing patients various e-Health applications which
      can be used any place and any time.

PMID- 15983842
TI  - [Status of telemedicine in Austria].
AB  - In an overview the situation of telemedicine in Austria is presented regarding
      the Austrian health service with the focus on patients. First the term
      "telemedicine" is defined according to the present definition of the European
      Union and the situation of the Austrian health service. Afterwards individual
      success components for the planning of telemedicine projects are presented. These
      are briefly shown by the "five-column concept" of the Tyrolean Government, which
      includes the medical, legal, economic, technical and quality management-oriented
      aspects during the planning and evaluation period of telemedicine projects. The
      conclusion gives an overview of individual committees and activities of the
      Austrian medical universities, the federation and states as well as individual
      Austrian telemedical societies.

PMID- 15983843
TI  - [European perspectives of health telematics].
AB  - The European perspectives of the present German developments in the field of
      health telematics are discussed critically. It is pointed out that technical
      projects have been financed with considerable means in the EU, however with out
      having any lasting effect on the value of health telematics in the health systems
      of Europe. A decisive cause is that the "health" topic was not codified in the
      Roman contracts. The international, global market is a crucial factor for
      international development and thus also for the orientation of the German
      projects and their economical and political success. The USA plays a dominant
      role on the global market. Caused by different reasons a corresponding market
      potential in the EU cannot be expected in the foreseeable future. With regard to
      the new options provided by telematics, it is therefore recommended that the
      national health services be reorganized, thus increasing quality and efficiency.
      With regard to progressively individualized medical care, the subject of "health"
      should afterwards be included in the European contracts. In the long run, an
      adjustment of the systems and uniform use of telematics could be achieved. Till
      then the coordination between the national governments in the area of health
      politics is seen as the most effective means for European integration.

PMID- 15983844
TI  - [Pathogenesis, diagnostics and treatment of Helicobacter pylori infection].
AB  - More than one-half of the world population is infected with Helicobacter pylori.
      Of those, approx. 500,000 die from gastric carcinoma every year. Ulcer disease,
      gastricatrophy and the rare MALT lymphoma are other sequelae of H. pylori
      infection. H. pylori possesses an array of virulence factors that include urease,
      flagellar motility, adhesins, the vacuolating cytotoxin VacA and the protein
      CagA. The gene encoding CagA is located on the cag pathogenicity island,
      comprising 29 genes the majority of which encodes components of a type IV
      secretion system capable of translocating CagA into epithelial cells where it
      interferes with cellular signal transduction processes. A number of diagnostic
      tests for H. pylori infection require gastroendoscopy. These include the biopsy
      urease test, histology, culture with susceptibility testing, and molecular
      detection methods such as fluorescent in situ hybridization. Non-invasive tests
      that do not require endoscopy include the (13)C urea breath test, H. pylori stool
      antigen ELISA and serology. The latter is unsuitable for treatment follow-up,
      since antibody titres persist up to a year after successful treatment. When
      patients have never been treated for H. pylori infection, biopsy urease test and
      histology are usually sufficient for diagnosis. In patients where endoscopy is
      not required, H. pylori infection can be reliably detected by (13)C urea breath
      test, stool antigen ELISA or serology. Patients who have under gone one or more
      unsuccessful cycles of eradication therapy in most cases harbour H. pylori
      resistant to one or several antibiotics. In these patients, culture and
      antibiotic susceptibility testing are indicated. Patients who have never been
      treated for H. pylori infection usually harbour susceptible strains. In such
      patients, classic "Italian" or "French" triple therapies may achieve eradication
      in >90% of cases. In the case of treatment failure, second-line antibiotic
      treatment regiments (rescue therapy) are used, optimally guided by susceptibility
      data.

PMID- 15983845
TI  - [Evidence-based medicine for the public].
AB  - The methods of evidence-based medicine demand high quality and up-to-date medical
      information. Ideally, this information is based on data from controlled clinical
      trials. When such external evidence is available, it provides a base for an
      effective patient-physician consultation, and is also essential for the consumer
      friendly presentation of medical information. This article sketches the
      international and German developments and approaches to preparing and maintaining
      evidence-based patient information and its influences on the models of physician
      patient communication.

PMID- 15983846
TI  - [Accidental rubella vaccination at the time of conception and in early
      pregnancy].

PMID- 15983847
TI  - [XV. International AIDS conference in Bangkok--AIDS in Asia has a thousand faces.
      3: Status of current therapy options and vaccine development].

PMID- 15983849
TI  - [Testing plasma donations for hepatitis B core antigen (anti-HBc) in order to
      improve safety of cellular blood components and of quarantined fresh frozen
      plasma].

PMID- 15983850
TI  - [Current recommendations for autologous hemotherapy].

PMID- 15983851
TI  - [Health assessment of plastics in the context of the food and consumer goods
      legislation].

PMID- 15983852
TI  - [Material monograph on di(2-ethylhexyl)phthalat (DEHP)--reference values for 5oxo
      MEHP und 5OH-MEHP in urine].

PMID- 15983853
TI  - [Classification of water endangering materials].

PMID- 15983854
TI  - Preoperative multimodality treatment of localized soft tissue sarcoma: addition
      through subtraction?

PMID- 15983855
TI  - Treatment of uterine artery vasospasm with transdermal nitroglycerin ointment
      during uterine artery embolization.
AB  - Uterine artery vasospasm can complicate uterine artery embolization (UAE) by
      prolonging procedure times or even causing treatment failure. Embolization must
      be delayed until the spasm improves and adequate antegrade flow in the vessel is
      restored. Vasospasm can also produce a "false endpoint" to the procedure, where
      stasis of flow in the vessel is falsely attributed to successful embolization but
      is actually the result of vasospasm, leading to undertreatment or treatment
      failure. Traditional treatments for uterine artery vasospasm have included
      transcatheter intra-arterial vasodilators and catheter withdrawal from the
      vessel, both of which can yield mixed results. We report a case of uterine artery
      vasospasm during UAE successfully treated with transdermal nitroglycerine
      ointment.

PMID- 15983856
TI  - Recanalization and stenting of an H-graft portacaval shunt.

PMID- 15983857
TI  - Tumor seeding following lung radiofrequency ablation: a case report.
AB  - Lung radiofrequency (RF) ablation was performed for the treatment of a primary
      lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast
      enhanced computed tomography (CT) study performed 3 months after RF ablation
      showed incomplete ablation of the lung tumor and the appearance of a chest wall
      tumor 4.0 cm in maximum diameter that was considered to be the result of needle
      tract seeding. RF ablation was performed for the treatment of both the lung and
      the chest wall tumors. Although tumor enhancement was eradicated in both of the
      treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases
      in both lungs 2 months after the second RF session. He is currently receiving
      systemic chemotherapy.

PMID- 15983858
TI  - Hematemesis due to a pseudoaneurysm of the splenic artery secondary to gastric
      tuberculosis.
AB  - Gastric tuberculosis (TB) is very rare compared with other sites in the
      gastrointestinal (GI) tract, and upper GI bleeding is an extremely rare
      manifestation of gastric TB. Also, a pseudoaneurysm is an uncommon cause of GI
      bleeding and is often encountered with pancreatitis. To our knowledge, no case of
      GI bleeding due to a pseudoaneurysm of the splenic artery secondary to gastric TB
      has been reported previously. We report a patient who presented with hematemesis
      due to a pseudoaneurysm of the splenic artery secondary to gastric TB.

PMID- 15983859
TI  - Pulmonary artery perforation repair during thrombectomy using microcoil
      embolization.
AB  - A distal pulmonary artery perforation was successfully occluded by percutaneous
      microcoil embolization via a microcatheter. Microcoil embolization is a
      reasonable alternative therapeutic approach for this rare complication of
      pulmonary interventional procedures.

PMID- 15983861
TI  - Evaluation of flood and landslide risk to the population of Italy.
AB  - We have compiled a database of floods and landslides that occurred in Italy
      between AD 1279 and 2002 and caused deaths, missing persons, injuries, and
      homelessness. Analysis of the database indicates that more than 50,593 people
      died, went missing, or were injured in 2580 flood and landslide events. Harmful
      events were inventoried in 26.3% of the 8103 Italian municipalities. Fatal events
      were most frequent in the Alpine regions of northern Italy and were caused by
      both floods and landslides. In southern Italy, landslides were the principal
      agents of fatalities and were most numerous in the Campania region. Casualties
      were most frequent in the autumn. Fast-moving landslides, including rock falls,
      rockslides, rock avalanches, and debris flows, caused the largest number of
      deaths. In order to assess the overall risk posed by these processes, we merged
      the historical catalogs and identified 2682 "hydrogeomorphological" events that
      triggered single or multiple landslides and floods. We estimated individual risk
      through the calculation of mortality rates for both floods and landslides and
      compared these rates to the death rates for other natural, medical, and human
      induced hazards in Italy. We used the frequency distribution of events with
      fatalities to ascertain the magnitude and frequency of the societal risks posed
      by floods and landslides. We quantified these risks in a Bayesian model that
      describes the probabilities of fatal flood and landslide events in Italy.

PMID- 15983860
TI  - Coastal zone problems and environmental strategies to be implemented at Edremit
      Bay, Turkey.
AB  - This case study examines the coastal zone problems focusing on the existing
      conflicts between tourism and commercial activities on the coasts of Edremit Bay,
      Turkey, and attempts to suggest solutions to these problems. Edremit Bay is a
      characteristic example of such a conflict in collective use of natural resources.
      The study area, with its 100-km-long sandy beach, naturally attracts different
      coastal user groups with different beneficial expectations: in terms of rest and
      recreation for one group and commercial gain offered in a variety of ways for
      another group. Significant coastal zone problems exist in the study area.
      Deterioration of shoreline due to tourism activities and illegal constructions,
      damage to the coastal ecosystem due to domestic/industrial wastewater discharges
      and some agricultural activities, and disordered urbanization are only a few of
      the many problems. The data presented here were partly derived from field study
      and partly collected from local state or private organizations. In this study, it
      is emphasized that there is a need for viable economic and environmental
      strategies to be designated in Edremit Bay, Turkey, in order to provide
      sustainable resource use. For this purpose, an integrated project together with a
      relevant planning chart including subprojects is also suggested. The success of a
      local environmental protection management project depends on active participation
      of all stakeholders including governmental organizations and nongovernmental
      organizations.

PMID- 15983862
TI  - Institutional challenges for EIA implementation in China: a case study of
      development versus environmental protection.
AB  - This paper provides a complete case study analysis of environmental impact
      assessment (EIA) implementation in China from planning to legal challenge, which
      is typical but rarely reported. The analysis takes an historical perspective on
      the regulatory and institutional structures through which EIA has been
      implemented in China, in order to evaluate the extent to which EIA has matured
      over the last 10 years. The case study relates to a proposed recreation/tourist
      development at Dianshan Lake, a protected water resource for Shanghai. Legal and
      administrative challenge began in 1993, when the case was initiated with a letter
      from the public, and concluded in 1996, when the case was decided in a court
      judgment. More recent follow-up research indicates that many issues have
      continued to be problems for EIA implementation in China. Policy implications in
      terms of regulatory structure, institutional arrangement, EIA procedure, EIA
      practitioners, and public participation can be drawn, and lessons learned for
      both the government and the developers. The study emphasizes the problem of
      relying on reorientation of existing institutions to promote new (environmental)
      priorities.

PMID- 15983863
TI  - Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar
      polychlorinated biphenyls in human milk in Osaka City, Japan.
AB  - Forty-eight human milk samples were collected from primiparous mothers in Osaka
      City from June 1999 to January 2000 and analyzed for polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like coplanar
      polychlorinated biphenyls (CoPCBs). Mean toxic equivalents (TEQs) in the milk
      were 13.86 pg I-TEQ/g fat or 16.50 pg World Health Organization (WHO)-TEQ/g fat
      for PCDDs and PCDFs; 9.87 pg WHO-TEQ/g fat for CoPCBs; and 23.74 pg TEQ/g fat
      using I-TEQ values of PCDDs and PCDFs or 26.36 pg TEQ/g fat using WHO-TEQ values
      of PCDDs and PCDFs for total PCDDs, PCDFs, and CoPCBs. The TEQ levels of these
      chemicals in human milk in Osaka City were in the range of levels in human milk
      surveyed in Japan, but the TEQ levels of PCDDs and PCDFs and total PCDDs, PCDFs,
      and CoPCBs from our study were slightly higher than average TEQ levels in human
      milk in Japan. When comparing our data with the latest data from the United
      States and some European countries, the TEQ levels of PCDDs and PCDFs in human
      milk from Osaka City were relatively high, whereas those of CoPCBs were ranked as
      being of intermediate level. Only TEQ values of CoPCBs in human milk were found
      to correlate with the increasing age of mothers and their estimated intake of
      seafood during the year before pregnancy. Concentrations of PCBs 105 and 118
      contributed to TEQ values of CoPCBs associated with seafood intake, whereas those
      of PCBs 156, 157, 114, 189, 167, and 169 contributed to TEQ values of CoPCBs
      associated with increasing maternal age.

PMID- 15983865
TI  - Horizontal transfer of two operons coding for hydrogenases between bacteria and
      archaea.
AB  - Using a phylogenetic approach, we discovered three putative horizontal transfers
      between bacterial and archaeal species involving large clusters of genes. One
      transfer involves an operon of 13 genes, called mbx, which probably was
      transferred into the genome of Thermotoga maritima from a species belonging or
      close to the Pyrococcus genus. The two others implied an operon of six genes,
      called ech, transferred independently to the genomes of Thermoanaerobacter
      tengcongensis and Desulfovibrio gigas, from a species belonging or close to the
      Methanosarcina genus. All these transfers affected operons coding for
      multisubunit membrane-bound (NiFe) hydrogenases involved in the energy metabolism
      of the donor genomes. The functionality of the transferred operons has not been
      experimentally demonstrated for T. maritima, whereas in D. gigas and T.
      tengcongensis the encoded multisubunit hydrogenase could have a role in energy
      conservation. This report adds several cases of horizontal gene transfers among
      hydrogenases already described.

PMID- 15983866
TI  - Adaptive diversification of vomeronasal receptor 1 genes in rodents.
AB  - The vomeronasal receptor 1 (V1R) are believed to be pheromone receptors in
      rodents. Here we used computational methods to identify 95 and 62 new putative
      V1R genes from the draft rat and mouse genome sequence, respectively. The rat V1R
      repertoire consists of 11 subfamilies, 10 of which are shared with the mouse,
      while rat appears to lack the H and I subfamilies found in mouse and possesses
      one unique subfamily (M). The estimations of the relative divergence times
      suggest that many subfamilies originated after the split of rodents and primates.
      The analysis also reveals that these clusters underwent an expansion very close
      to the split of mouse and rat. In addition, maximum likelihood analysis showed
      that the nonsynonymous and synonymous rate ratio for most of these clusters was
      much higher than one, suggesting the role of positive selection in the
      diversification of these duplicated V1R genes. Because V1R are thought to mediate
      the process of signal transduction in response to pheromone detection, we
      speculate that the V1R genes have evolved under positive Darwinian selection to
      maintain the ability to discriminate between large and complex pheromonal
      mixtures.

PMID- 15983867
TI  - Explosive lineage-specific expansion of the orphan nuclear receptor HNF4 in
      nematodes.
AB  - The nuclear receptor superfamily expanded in at least two episodes: one early in
      metazoan evolution, the second within the vertebrate lineage. An exception to
      this pattern is the genome of the nematode Caenorhabditis elegans, which encodes
      more than 270 nuclear receptors, most of them highly divergent. We generated 128
      cDNA sequences for 76 C. elegans nuclear receptors, confirming that these are
      active genes. Among these numerous receptors are 13 orthologues of nuclear
      receptors found in arthropods and/or vertebrates. We show that the supplementary
      nuclear receptors (supnrs) originated from an explosive burst of duplications of
      a unique orphan receptor, HNF4. This origin has specific implications for the
      role of ligand binding in the function and evolution of the nematode
      supplementary nuclear receptors. Moreover, the supplementary nuclear receptors
      include a group of very rapidly evolving genes found primarily on chromosome V.
      We propose a model of lineage-specific duplications from a chromosome on which
      duplication and substitution rates are highly increased. Our results provide a
      framework to study nuclear receptors in nematodes, as well as to consider the
      functional and evolutionary consequences of lineage-specific duplications.

PMID- 15983868
TI  - Sequence variation in the tRNA genes of human mitochondrial DNA.
AB  - Recent analyses have shown that nonsynonymous variation in human mitochondrial
      DNA (mtDNA) contains nonneutral variants, suggesting the presence of mildly
      deleterious mutations. Many of the disease-causing mutations in mtDNA occur in
      the genes encoding the tRNAs. Nucleotide sequence variation in these genes has
      not been studied in human populations, nor have the structural consequences of
      nucleotide substitutions in tRNA molecules been examined. We therefore determined
      the nucleotide sequences of the 22 tRNA genes in the mtDNA of 477 Finns and,
      also, obtained 435 European sequences from the MitoKor database. No differences
      in population polymorphism indices were found between the two data sets. We
      assessed selective constraints against various tRNA domains by comparing allele
      frequencies between these domains and the synonymous and nonsynonymous sites,
      respectively. All tRNA domains except the variable loop were more conserved than
      synonymous sites, and T stem and D stem were more conserved than the respective
      loops. We also analyzed the energetic consequences of the 96 polymorphisms
      recovered in the two data sets or in the Mitomap database. The minimum free
      energy (DeltaG) was calculated using the free energy rules as implemented in
      mfold version 3.1. The DeltaG's were normally distributed among the 22 wild-type
      tRNA genes, whereas the 96 polymorphic tRNAs departed significantly from a normal
      distribution. The largest differences in DeltaG between the wild-type and the
      polymorphic tRNAs in the Finnish population tended to be in the polymorphisms
      that were present at low frequencies. Allele frequency distributions and minimum
      free energy calculations both suggested that some polymorphisms in tRNA genes are
      nonneutral.

PMID- 15983869
TI  - Different epidemic potentials of the HIV-1B and C subtypes.
AB  - HIV, the cause of AIDS in humans, is characterized by great genetic
      heterogeneity. In particular, HIV-1 group M subtypes are responsible for most of
      the infections worldwide. We investigate the demographic history of HIV-1B and
      HIV-1C subtypes in South Africa and Brazil using both a parametric and a
      nonparametric approach based on coalescent theory. Our results show that although
      both subtypes are spreading exponentially in Brazil, the HIV-1C growth rate is
      about twice that of Brazilian HIV-1B or South African HIV-1C, providing evidence,
      for the first time, of a different epidemic potential between two HIV-1 subtypes.
      The present study not only may have important consequences for devising future
      vaccination and therapeutic strategies, but also offers additional evidence that
      skyline plots are indeed a simple and powerful tool for monitoring and predicting
      the behavior of viral epidemics.

PMID- 15983870
TI  - Molecular evolution of prolactin in primates.
AB  - Pituitary prolactin, like growth hormone (GH) and several other protein hormones,
      shows an episodic pattern of molecular evolution in which sustained bursts of
      rapid change contrast with long periods of slow evolution. A period of rapid
      change occurred in the evolution of prolactin in primates, leading to marked
      sequence differences between human prolactin and that of nonprimate mammals. We
      have defined this burst more precisely by sequencing the coding regions of
      prolactin genes for a prosimian, the slow loris (Nycticebus pygmaeus), and a New
      World monkey, the marmoset (Callithrix jacchus). Slow loris prolactin is very
      similar in sequence to pig prolactin, so the episode of rapid change occurred
      during primate evolution, after the separation of lines leading to prosimians and
      higher primates. Marmoset prolactin is similar in sequence to human prolactin, so
      the accelerated evolution occurred before divergence of New World monkeys and Old
      World monkeys/apes. The burst of change was confined largely to coding sequence
      (nonsynonymous sites) for mature prolactin and is not marked in other components
      of the gene sequence. This and the observations that (1) there was no apparent
      loss of function during the episode of rapid evolution, (2) the rate of evolution
      slowed toward the basal rate after this burst, and (3) the distribution of
      substitutions in the prolactin molecule is very uneven support the idea that this
      episode of rapid change was due to positive adaptive selection. In the slow loris
      and marmoset there is no evidence for duplication of the prolactin gene, and
      evidence from another New World monkey (Cebus albifrons) and from the chimpanzee
      and human genome sequences, suggests that this is the general position in
      primates, contrasting with the situation for GH genes. The chimpanzee prolactin
      sequence differs from that of human at two residues and comparison of human and
      chimpanzee prolactin gene sequences suggests that noncoding regions associated
      with regulating expression may be evolving differently from other noncoding
      regions.

PMID- 15983871
TI  - Structure, evolution, and expression of the two invertase gene families of rice.
AB  - Invertases catalyze the irreversible hydrolysis of sucrose to glucose and
      fructose. Plants contain two unrelated families of these enzymes: acid forms that
      derive from periplasmic invertases of eubacteria and are found in cell wall and
      vacuole, and neutral/alkaline forms evolved from the cytosolic invertases of
      cyanobacteria. Genomes of rice (Oryza sativa) and thale cress (Arabidopsis
      thaliana) contain multiple genes encoding these two families. Here for rice we
      identify the member genes of a cell-wall group (designated OsCIN1-9), a vacuolar
      group (OsVIN1-2), and two ancient neutral/alkaline groups: alpha (OsNIN1-4) and
      beta (OsNIN5-8). In Arabidopsis these groups contain six, two, four and five
      members, respectively. It is believed that the vacuolar group evolved from the
      cell-wall group. We provide evidence that the N-terminal signal peptide that
      directs cell-wall invertases co-translationally into the endoplasmic reticulum
      for secretion was replaced in the vacuolar group by a sequence similar to the
      complex N-terminal motif that targets alkaline phosphatase post-translationally
      to the vacuolar membrane of yeast. Since the last common ancestor of Arabidopsis
      and rice, the two invertase families evolved equally rapidly via gene duplication
      and gene loss, but the acid invertase family underwent approximately 10 events of
      intron loss compared with a single event of intron gain in the neutral/alkaline
      invertase family. Transcripts were detected for all rice invertase genes except
      OsCIN9. The acid invertase genes showed greater spatial and temporal diversity of
      expression than the neutral/alkaline genes.

PMID- 15983872
TI  - Grass evolution inferred from chromosomal rearrangements and geometrical and
      statistical features in RNA structure.
AB  - The grasses (Poaceae) represent a monophyletic lineage that arose about 70
      million years ago. The lineage contains about 10,000 species that differ widely
      in morphology and physiology. Species show striking differences in genome size, a
      feature important in the context of conservation of gene content and order
      (synteny and colinearity) and in the extension of genomic information directly
      from one grass species to another using comparative approaches. Grass
      diversification has been a contentious issue, as the exact branching order of the
      various subfamilies has been difficult to establish with standard methods. This
      motivated an evolutionary study of deep phylogenetic relationships based on the
      structure of coding and non-coding RNA molecules and on chromosomal
      rearrangements. Phylogenetic relationships in the grass family were inferred
      directly from the structure of RNA using cladistic principles and considerations
      in statistical mechanics. Coded attributes describing topological and
      thermodynamic information embedded in RNA molecules were treated as linearly
      ordered multi-state characters and were polarized by fixing the direction of
      character transformation toward molecular order. Intrinsically rooted phylogenies
      derived from the structure of signal recognition particle (SRP) RNA, the mRNA
      encoded by the early nodulation gene enod40, the small subunit of ribosomal RNA
      (rRNA), and the internal transcribed spacer ITS1 of rRNA established an order for
      the diversification of major grass lineages, suggesting a sister relationship of
      the Pooideae and the PACCAD clade. This same conclusion was reached when large
      scale chromosomal rearrangements derived from the comparative genetic mapping of
      cereal genomes were studied. Chromosomal complements aligned in the most
      parsimonious manner allowed identification and coding of characters depicting
      chromosomal translocations, insertions, and linkage block arrangements and the
      reconstruction of phylogenetic trees based on large-scale chromosomal structure.
      Congruent reconstruction of deep branching relationships using geometrical and
      statistical features of RNA structure and orthology and large scale chromosomal
      recombination events support assumptions of polarization in character
      argumentation, and fail to falsify the claim that extant grass chromosomes can be
      considered combinations of linkage blocks of an ancestor of the rice genome.
      Congruence also suggests that the universal tendency toward order in RNA and the
      search for the most parsimonious organization of be genome architecture appear to
      be mutually supported drivers of molecular evolution. The study clarifies the
      relationship of major clades in the grasses, shows that phylogenetic history can
      be reconstructed effectively from the combinatorial exchange of chromosomal
      linkage blocks, and reveals considerable phylogenetic signal embedded in the
      structure of signal polypeptide-coding mRNA molecules, describing an instance
      where mRNA structure is the subject of strong evolutionary constraint.

PMID- 15983873
TI  - The alpha-globin gene family of an Australian marsupial, Macropus eugenii: the
      long evolutionary history of the theta-globin gene and its functional status in
      mammals.
AB  - Comparative evolutionary analyses of gene families among divergent lineages can
      provide information on the order and timing of major gene duplication events and
      evolution of gene function. Here we investigate the evolutionary history of the
      alpha-globin gene family in mammals by isolating and characterizing alpha-like
      globin genes from an Australian marsupial, the tammar wallaby, Macropus eugenii.
      Sequence and phylogenetic analyses indicate that the tammar alpha-globin family
      consists of at least four genes including a single adult-expressed gene (alpha),
      two embryonic/neonatally expressed genes (zeta and zeta'), and theta-globin, each
      orthologous to the respective alpha-, zeta-, and theta-globin genes of eutherian
      mammals. The results suggest that the theta-globin lineage arose by duplication
      of an ancestral adult alpha-globin gene and had already evolved an unusual
      promoter region, atypical of all known alpha-globin gene promoters, prior to the
      divergence of the marsupial and eutherian lineages. Evolutionary analyses, using
      a maximum likelihood approach, indicate that theta-globin, has evolved under
      strong selective constraints in both marsupials and the lineage leading to human
      theta-globin, suggesting a long-term functional status. Overall, our results
      indicate that at least a four-gene cluster consisting of three alpha-like and one
      beta-like globin genes linked in the order 5'-zeta-alpha-theta-omega-3' existed
      in the common ancestor of marsupials and eutherians. However, results are
      inconclusive as to whether the two tammar zeta-globin genes arose by duplication
      prior to the radiation of the marsupial and eutherian lineages, with maintenance
      of exon sequences by gene conversion, or more recently within marsupials.

PMID- 15983874
TI  - Molecular evolution of duplicated ray finned fish HoxA clusters: increased
      synonymous substitution rate and asymmetrical co-divergence of coding and non
      coding sequences.
AB  - In this study the molecular evolution of duplicated HoxA genes in zebrafish and
      fugu has been investigated. All 18 duplicated HoxA genes studied have a higher
      non-synonymous substitution rate than the corresponding genes in either bichir or
      paddlefish, where these genes are not duplicated. The higher rate of evolution is
      not due solely to a higher non-synonymous-to-synonymous rate ratio but to an
      increase in both the non-synonymous as well as the synonymous substitution rate.
      The synonymous rate increase can be explained by a change in base composition,
      codon usage, or mutation rate. We found no changes in nucleotide composition or
      codon bias. Thus, we suggest that the HoxA genes may experience an increased
      mutation rate following cluster duplication. In the non-Hox nuclear gene RAG1
      only an increase in non-synonymous substitutions could be detected, suggesting
      that the increased mutation rate is specific to duplicated Hox clusters and might
      be related to the structural instability of Hox clusters following duplication.
      The divergence among paralog genes tends to be asymmetric, with one paralog
      diverging faster than the other. In fugu, all b-paralogs diverge faster than the
      a-paralogs, while in zebrafish Hoxa-13a diverges faster. This asymmetry
      corresponds to the asymmetry in the divergence rate of conserved non-coding
      sequences, i.e., putative cis-regulatory elements. These results suggest that the
      5' HoxA genes in the same cluster belong to a co-evolutionary unit in which genes
      have a tendency to diverge together.

PMID- 15983875
TI  - BoS: a large and diverse family of short interspersed elements (SINEs) in
      Brassica oleracea.
AB  - Short interspersed elements (SINEs) are nonautonomous non-LTR retrotransposons
      that populate eukaryotic genomes. Numerous SINE families have been identified in
      animals, whereas only a few have been described in plants. Here we describe a new
      family of SINEs, named BoS, that is widespread in Brassicaceae and present at
      approximately 2000 copies in Brassica oleracea. In addition to sharing a modular
      structure and target site preference with previously described SINEs, BoS
      elements have several unusual features. First, the head regions of BoS RNAs can
      adopt a distinct hairpin-like secondary structure. Second, with 15 distinct
      subfamilies, BoS represents one of the most diverse SINE families described to
      date. Third, several of the subfamilies have a mosaic structure that has arisen
      through the exchange of sequences between existing subfamilies, possibly during
      retrotransposition. Analysis of BoS subfamilies indicate that they were active
      during various time periods through the evolution of Brassicaceae and that active
      elements may still reside in some Brassica species. As such, BoS elements may be
      a valuable tool as phylogenetic makers for resolving outstanding issues in the
      evolution of species in the Brassicaceae family.

PMID- 15983876
TI  - On the structural differences between markers and genomic AC microsatellites.
AB  - AC microsatellites have proved particularly useful as genetic markers. For some
      purposes, such as in population biology, the inferences drawn depend on the
      quantitative values of their mutation rates. This, together with intrinsic
      biological interest, has led to widespread study of microsatellite mutational
      mechanisms. Now, however, inconsistencies are appearing in the results of marker
      based versus non-marker-based studies of mutational mechanisms. The reasons for
      this have not been investigated, but one possibility, pursued here, is that the
      differences result from structural differences between markers and genomic
      microsatellites. Here we report a comparison between the CEPH AC marker
      microsatellites and the global population of AC microsatellites in the human
      genome. AC marker microsatellites are longer than the global average. Controlling
      for length, marker microsatellites contain on average fewer interruptions, and
      have longer segments, than their genomic counterparts. Related to this, marker
      microsatellites show a greater tendency to concentrate the majority of their
      repeats into one segment. These differences plausibly result from scientists
      selecting markers for their high polymorphism. In addition to the structural
      differences, there are differences in the base composition of flanking sequences,
      marker flanking regions being richer in C and G and poorer in A and T. Our
      results indicate that there are profound differences between marker and genomic
      microsatellites that almost certainly affect their mutation rates. There is a
      need for a unified model of mutational mechanisms that accounts for both marker
      derived and genomic observations. A suggestion is made as to how this might be
      done.

PMID- 15983877
TI  - [The new jurisdiction on care -- changes in the law on care-giving based on the
      2nd Betreuungsrechtsanderungsgesetz].

PMID- 15983878
TI  - [The craft of psychiatric evaluation].

PMID- 15983883
TI  - [Unsatisfied relatives -- malpractice of psychiatric care or economic
      necessity?].

PMID- 15983884
TI  - [For and against: do anti-stigma campaigns make sense?].

PMID- 15983885
TI  - [The stigma of mental illness: concepts, forms, and consequences].
AB  - OBJECTIVE: Persons with mental illness frequently encounter public stigma and may
      suffer from self-stigma. We aim to clarify the concept of mental illness stigma
      and discuss important consequences for people with mental illness. METHOD: A
      search of scientific literature on mental illness stigma was conducted with a
      focus on conceptually relevant empirical studies. RESULTS: After giving a
      conceptual overview of stigma, we elaborate on the consequences of stigma,
      focussing on self-stigma/empowerment, coping behaviour, fear of stigma as a
      barrier to using health services, and on structural discrimination. Main
      strategies to reduce stigma -- protest, education, and contact -- are discussed.
      CONCLUSIONS: Stigma is of central importance to persons with mental illness, both
      to how they experience their illness and its consequences and whether they use
      available health services. Well-designed anti-stigma initiatives will help to
      diminish the impact of mental illness stigma.

PMID- 15983886
TI  - [Everyday burden of mentally ill people's spouses -- client orientated approaches
      in relatives' support].
AB  - OBJECTIVE: Regarding clinical practice groups for relatives of mentally ill
      people mostly are conceptualized depending on the type of disorder the patient is
      suffering from. However, results of research on burden of caregivers indicate
      aspects of burden which do not seem to be associated with the patients' disorder.
      METHOD: As part of a study on the burden of caregiving to mentally ill family
      members in-depth interviews as well as diary writing over a 12 weeks period were
      carried out with 6 spouses of patients suffering from schizophrenia or
      depression. RESULTS: Differences in the burden of caregiving do not seem to be
      related to the type of the patients' diagnosis. Aspects of partnership dominated
      the interviews and diary writing of the spouses. In all cases substantial parts
      of experienced burden are related to the spouses' efforts to share mastering of
      the illness with the patient. CONCLUSIONS: The hypothesis of specific aspects
      regarding the type of the patients' disorder related to spouses caregiver burden
      can not be supported by the results of this study. However, our results seem to
      encourage aspects of relationship within the development of support programs for
      relatives of mentally ill people.

PMID- 15983887
TI  - [7-year-follow-up investigations of the geriatric psychiatric inpatient service
      in a separated care at a state hospital (obligatory service) and an integrated
      care at a university hospital in Goettingen, Germany -- I. Type of patients].
AB  - OBJECTIVE: 7 years after our first investigation we were interested in the
      stability versus (trends of) change in geriatric psychiatric inpatients while the
      structure of services was mainly unchanged. METHOD: We performed standardised
      chart reviews of randomly selected groups of geriatric psychiatric inpatients who
      had been treated in 1998 and 1999 in the Psychiatric University Hospital (PUK; n
      = 104) or the Psychiatric State Hospital (LKH; n = 100), which together treat all
      psychiatric inpatients in the region. With regard to age, the PUK provides
      integrated and the LKH separated care. RESULTS: Mean patients' age decreased.
      Compulsory admissions according to state laws decreased significantly. Specialist
      treatment before admission decreased. Premedication showed a dramatic decrease of
      antidementia drug treatment and a nearly unchanged high rate of prescriptions of
      antipsychotics and benzodiazepines. CONCLUSION: With a lower age and lower rate
      of specialist treatment we could not find signs of a better outpatient care
      preceding hospital admission during follow-up.

PMID- 15983888
TI  - [7-year-follow-up investigations and comparison of the geriatric psychiatric
      inpatient service in a separated care at a state hospital (obligatory service)
      and an integrated care at a university hospital in Goettingen, Germany -- II.
      Diagnosis and treatment].
AB  - OBJECTIVE: By use of a 7-y-follow-up investigation of differences between
      geriatric psychiatric patients and their management in an integrated (with other
      adult age groups) care in the University Psychiatric Hospital (PUK) compared to
      those in a separated (only according to age) care in the Psychiatric State
      Hospital (LKH), which together treat all psychiatric inpatients in Goettingen,
      Germany, we wanted to show, whether progress can be made visible. METHOD: We
      performed standardized chart reviews of randomly selected groups of patients, who
      had been treated in the PUK (n = 104) and the LKH (n = 100) in the years 1998 and
      1999. RESULTS: Again, organic brain diseases/dementia was the most frequent
      diagnosis in the LKH and depression that of the PUK. Less diagnostics were
      applied compared to the previous investigation, especially neuroimaging. Non-drug
      treatments are (documented) more frequently now in the LKH. Both institutions -
      data with respect to frequent syndromes are given - treated the wide majority of
      patients with psychoactive drugs, especially neuroleptics, typical
      antidepressants, benzodiazepines. Antidementia drugs were given significantly
      less. Hospital stays decrease in length. Compared to the respective investigation
      in Magdeburg there is some evidence supporting specialized care for the elderly.
      CONCLUSION: Budgetary restrictions could also be shown in inpatient treatment.
      Progress in specific drug treatment does not reach the patients as much as
      necessary.

PMID- 15983889
TI  - [Self-immolation as an effort of self-rescue during a psychotic episode].
AB  - Self-immolation as reported in the literature usually happens in the context of
      suicide acts or political martyrdom. We report a case in which a patient during a
      first psychotic episode attempted to immolate herself: she covered her legs with
      pieces of clothing and set them a fire. Severe burning made amputation of both
      her legs necessary, one above, one below the knee. The patient had not acted in
      this way in order to die, but to save herself from the impending end of the
      world. She was convinced the earth was going to explode, and she would only be
      able to flee to Venus by self-immolation. She acted under the influence of
      imperative acoustic hallucinations encouraging her and pressing her to proceed.
      Antipsychotic treatment with clozapine resulted in complete remission of all
      psychotic symptoms. Other than during psychosis the patient didn't believe in
      life on other planets, had no fantasies about the end of the earth, no contact
      with sects and no religious or cultural motives for self-immolation.

PMID- 15983891
TI  - Salvage therapy with ritonavir-boosted amprenavir/fosamprenavir: virological and
      immunological response in two years follow-up.
AB  - OBJECTIVE: To evaluate the efficacy of salvage regimens containing ritonavir
      boosted amprenavir (APV/r) or fosamprenavir (FPV/r) in heavily pretreated
      protease inhibitor (PI)-experienced HIV-1 patients. METHOD: Evaluation of APV/r-
      or FPV/r-containing antiretroviral regimens in PI-experienced HIV-1 patients with
      2 or more antiretroviral failures. Follow-up continued to 96 weeks with
      prospective collection of data. RESULTS: 54 episodes (48 on APV/r and 6 on FPV/r)
      were considered in 45 patients who had received a median of 5 prior
      antiretroviral regimens (range, 2-13) including a median of 3 PIs (range, 2-4).
      Median time of treatment at analysis was 72 weeks (range, 12-210). At baseline,
      plasma viral load (pVL) and CD4 cell count was 67,000 copies/mL and 167
      cell/mm(3), respectively. At week 96, the median pVL was < 50 copies/mL and CD4
      cell count was 519 cells/mm(3). Proportion of patients with pVL below detection
      was 62% at week 48 and 61% at week 96. Fifteen patients stopped treatment because
      of virologic failure; one presented a full resistance profile to APV/r, based on
      the ANRS 2003 resistance algorithm. Median trough APV plasma concentration 4
      weeks after treatment initiation was 1406 ng/mL (range, 452-4321); dose
      adaptation was required in only 7 patients. CONCLUSION: This study provides long
      term follow-up of APV/r and FPV/r in the setting of salvage therapy, showing a
      high and sustained rate of virologic and immunologic response.

PMID- 15983890
TI  - Virologic and immunologic response to a boosted double-protease inhibitor-based
      therapy in highly pretreated HIV-1-infected patients.
AB  - PURPOSE: To assess the virologic and immunologic response to a boosted double
      protease inhibitor (PI) regimen of highly pretreated patients infected with HIV-1
      and to examine the role of PI resistance and concentration of serum saquinavir.
      METHOD: In an open-label prospective study, lopinavir/ritonavir, saquinavir-sgc,
      lamivudine, and other nucleoside analogues were offered to highly pretreated
      patients who had advanced HIV-1 infection and who had failed at least 2 previous
      highly active antiretroviral therapy regimens including at least 1 nonnucleoside
      reverse transcriptase inhibitor. The relationship between baseline drug
      resistance and steady-state saquinavir serum levels and early (week 4) and
      sustained (week 48) virologic response was documented. RESULTS: 35 advanced HIV-1
      patients were enrolled. The boosted double-PI regimen was well tolerated. Twenty
      two (63%) of the 35 patients had a > 0.8 log(10) decrease in HIV viral load at
      week 4. After 48 weeks of follow-up, the 22 patients who remained on the study
      therapy had an average decrease in viral load of 1 log(10) and had a median
      increase in CD4 cells of 60 cell/microL. Multiple logistic regression analysis
      indicated that genotypic resistance to both PIs and the week-3 trough
      concentrations of saquinavir were associated with virologic outcome at week 4.
      The presence of > or = 6 lopinavir mutations [odds ratio (OR) 0.03; 95% CI 0.01
      to 0.79] and the 48V mutation (OR 0.01; 95%CI <0.01 to 0.88) was independently
      associated with lower odds of achieving an early response, whereas a higher
      saquinavir concentration at week 3 (OR 8.36; 95% CI 1.28 to 54.70) was associated
      with greater odds of an early response. CONCLUSION: These findings suggest that
      baseline PI resistance and saquinavir concentration were associated with
      virologic response and should be considered when planning salvage therapy.

PMID- 15983892
TI  - Evaluation of multiple failure time analyses of observational data in patients
      treated for HIV.
AB  - The development of protease inhibitors and nonnucleoside reverse transcriptase
      inhibitors has substantially increased the number of combinations available for
      multi-drug therapies in human immunodeficiency virus (HIV) infection.
      Unfortunately, all antiretroviral therapies lose efficacy over time or induce
      side effects, thus making secondary and tertiary alternatives necessary. With the
      multiplicity of multi-drug combination therapies, the challenge is to determine
      which multi-drug combination to use as initial therapy and which to use as
      subsequent therapy to maximize survival. No standard methodologic approach has
      been developed to answer this question within the context of observational
      clinical HIV data. We demonstrate the use of semi-parametric models employing
      repeated, multiple failure time analysis to compare the relative efficacy of
      treatments containing zidovudine, stavudine, or other multi-drug combinations for
      patients in the CHORUS (Collaborations in HIV Outcomes Research - US) database.

PMID- 15983893
TI  - Cost-effectiveness of enfuvirtide for treatment-experienced patients with HIV in
      Italy.
AB  - BACKGROUND: Enfuvirtide (ENF) plus an optimized background (OB) antiretroviral
      regimen delays virological failure (VF), reduces HIV-1 viral load, and increases
      CD4 count compared with OB only in pretreated patients. PURPOSE: To forecast long
      term outcomes, costs, and cost-effectiveness of ENF+OB vs. OB in the Italian
      health care system. METHOD: A Markov model was developed and clinical trial
      results on viral suppression and CD4 count were linked with data from HAART-era
      studies of the risk of AIDS-defining events (ADEs) and death. Resource data were
      obtained from Italian sources on direct medical costs. Cost-effectiveness was
      computed as the incremental cost per quality-adjusted life year (QALY) saved.
      RESULTS: Patients receiving ENF+OB were projected to experience a mean time to
      virological failure of 1.0 years vs. 0.5 years for OB and mean time to
      immunological failure of 3.1 years vs. 1.3 years for OB. Life expectancy and
      QALYs were greater for ENF+OB than OB by 1.8 and 1.5 years, respectively. Total
      lifetime medical cost was euro 126,487 for ENF+OB and euro 84,416 for OB, a
      difference of euro 42,071 due to the cost of ENF itself (euro 18,400) and the
      medical costs associated with additional life expectancy (euro 23,671). The
      incremental cost-effectiveness of ENF+OB was euro 23,721 per life year (euro
      28,669 per QALY). CONCLUSION: ENF+OB is predicted to increase life expectancy at
      a cost per life year that is comparable to many well-accepted therapies in
      Europe.

PMID- 15983894
TI  - Hepatitis C viremia in HIV/HCV-coinfected patients: lower levels in presence of
      chronic hepatitis B.
AB  - Complex reciprocal interactions between hepatitis C (HCV) and hepatitis B (HBV)
      viruses (HBV) have been reported. We examined the influence of HBV on HCV RNA
      titers in 376 HCV/HIV-coinfected patients (30 were also HBsAg positive).
      Regression analyses identified negative HBsAg and male sex as factors associated
      with HCV RNA values >500,000 IU/mL.

PMID- 15983895
TI  - Pilot study of saquinavir and lopinavir/ritonavir twice daily in protease
      inhibitor-naive HIV-positive patients.
AB  - PURPOSE: Protease inhibitor (PI)-naive patients may have limited reverse
      transcriptase inhibitor (RTI) options due to resistance and/or toxicity.
      Effective, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI)
      sparing regimens are therefore needed. METHOD: This prospective study evaluated
      the efficacy and safety of saquinavir/lopinavir/ritonavir (1000/400/100 mg bid)
      in PI-naive patients over 48 weeks. The regimen could be intensified with NRTIs
      if patients did not achieve virologic suppression by 12 weeks. The primary study
      endpoint was virologic suppression at 48 weeks. Additional study objectives
      included assessment of safety, CD4 cell counts, blood lipids, PI trough levels,
      and anthropometrics. RESULTS: Of the 20 PI-naive study participants, 16 completed
      48 weeks of study treatment, with no discontinuations attributed to virologic
      failure. Fourteen of 16 patients achieved virologic suppression with only the
      PIs; 2 patients required tenofovir intensification to achieve complete
      suppression. Median CD4 counts increased significantly over 48 weeks. Adverse
      events were generally mild and manageable. Extreme lipid elevations were
      uncommon, although moderate lipid elevations occurred in the majority of
      patients. Most patients reported some degree of central fat accumulation.
      CONCLUSION: Our study demonstrates that saquinavir/lopinavir/ritonavir
      1000/400/100 mg bid with tenofovir intensification is a potent nucleoside-sparing
      regimen for PI-naive patients, associated with durable HIV suppression and
      improved CD4 cell counts. Fat accumulation and metabolic changes observed in this
      study warrant confirmation from ongoing trials.

PMID- 15983896
TI  - Highlights from the 1st International Workshop on HIV and Hepatitis Co-infection.

PMID- 15983897
TI  - Tumor necrosis factor inhibition and opportunistic infections.

PMID- 15983898
TI  - Tumor necrosis factor and chemokine interactions in the formation and maintenance
      of granulomas in tuberculosis.
AB  - Inflammatory cells migrate to the lungs in response to Mycobacterium tuberculosis
      infection. These infiltrating cells organize into a structure called a granuloma,
      which controls and contains infection. The signals that influence the formation
      of granulomas are largely unknown. Tumor necrosis factor (TNF) has been
      demonstrated to be required for formation of granulomas, in mouse models of
      tuberculosis, and for control of latent tuberculosis, in humans. We investigated
      the mechanisms by which TNF controls cell migration in response to M.
      tuberculosis infection, focusing on the effects of this cytokine on chemokine
      expression. Chemokines are small molecules that direct the migration of cells
      within the body. Our data support the notion that TNF is required for appropriate
      chemokine expression by M. tuberculosis-infected macrophages, both in vitro and
      in vivo.

PMID- 15983899
TI  - Reactivation of latent granulomatous infections by infliximab.
AB  - Although infliximab and etanercept share tumor necrosis factor (TNF) as a common
      therapeutic target, accumulating data indicate that infliximab (an anti-TNF
      monoclonal antibody) poses a greater risk of reactivation of latent granulomatous
      infections than does etanercept (a soluble TNF receptor). Similarly, infliximab
      is effective for the treatment of chronic granulomatous inflammatory conditions
      (e.g., Crohn disease) for which etanercept is ineffective. The ability of
      infliximab to disrupt established granulomas may be distinct from its ability to
      neutralize soluble TNF. Further research to elucidate the mechanism of the
      antigranuloma activity of infliximab is warranted.

PMID- 15983900
TI  - Tumor necrosis factor and its blockade in granulomatous infections: differential
      modes of action of infliximab and etanercept?
AB  - Tumor necrosis factor (TNF) is a critical component of both the antibacterially
      protective and the inflammatory responses against infections, particularly
      infections with intracellularly viable microorganisms. It is, therefore, not
      surprising that some treatment regimens that target TNF function have resulted in
      an increase in complications associated with infections due to such pathogens as
      Mycobacterium tuberculosis, Listeria monocytogenes, and Histoplasma capsulatum;
      organized granuloma formation is required to keep such infections under control.
      However, treatment with anti-TNF monoclonal antibodies (i.e., infliximab) has
      been associated with a higher incidence of granulomatous infections than has
      treatment with a TNF receptor (TNFR) p75 immunoglobulin G-fusion construct (i.e.,
      etanercept). Three hypotheses concerning the mode of action of these 2 agents
      that might explain this difference are discussed here: differential induction of
      apoptosis or lysis in membrane TNF-expressing macrophages and T cells,
      differential inhibition of signaling via TNFRp55 and TNFRp75, and different net
      neutralizing capacities resulting from different pharmacologic properties.

PMID- 15983901
TI  - Modulation of infection with Histoplasma capsulatum by inhibition of tumor
      necrosis factor-alpha activity.
AB  - Tumor necrosis factor (TNF)-alpha is required for host defenses against a number
      of pathogenic microbes, including Histoplasma capsulatum. In mice, TNF-alpha is
      necessary for the generation of a protective immune response to both primary and
      secondary histoplasmosis. Recent reports indicate that, in humans, treatment with
      inhibitors of TNF-alpha is associated with disseminated histoplasmosis. Here, I
      review the mechanisms by which inhibition of TNF-alpha may exacerbate infection
      with H. capsulatum.

PMID- 15983902
TI  - Tumor necrosis factor inhibition and invasive fungal infections.
AB  - Candida albicans and Aspergillus fumigatus occur ubiquitously in nature; C.
      albicans is part of the natural flora of most healthy individuals, and A.
      fumigatus is commonly found in soil, plant debris, and indoor air. Neither fungus
      poses a threat to healthy individuals, but each can cause fatal infections in
      immunocompromised patients. The use of tumor necrosis factor (TNF) antagonists
      for the treatment of rheumatoid arthritis and other autoimmune diseases has been
      associated with an increased incidence of opportunistic infections, including
      infections with both of these fungi. Because the use of TNF antagonists is
      expected to increase in the future, understanding the role that TNF plays and the
      effect of its antagonism on host defense against infections with these fungi is
      critical for reducing the associated morbidity and mortality.

PMID- 15983903
TI  - Defective innate antibacterial host responses during murine Klebsiella pneumoniae
      bacteremia: tumor necrosis factor (TNF) receptor 1 deficiency versus therapy with
      anti-TNF-alpha.
AB  - Klebsiella pneumoniae is a leading cause of pneumonia due to gram-negative
      bacteria. A significant clinical complication of pulmonary infection with K.
      pneumoniae is peripheral blood dissemination, which results in a systemic
      infection coincident with the localized pulmonary infection. This study describes
      the critical importance of tumor necrosis factor (TNF) receptor 1 (TNFR1)
      mediated signaling during K. pneumoniae bacteremia. TNFR1-deficient mice
      displayed a significantly increased mortality rate after intravenous inoculation.
      Unexpectedly, this increased mortality occurred in the absence of either
      increased bacterial burden or increased liver injury. However, excessive
      production of proinflammatory cytokines, including TNF-alpha , was observed in
      TNFR1-deficient mice, compared with that observed in infected C57BL/6 mice, which
      suggests that production was dysregulated in the absence of TNFR1 signaling. In
      contrast, other experiments examined the effect of immunotherapy with anti-TNF
      alpha during K. pneumoniae bacteremia. Administration of a neutralizing anti-TNF
      alpha antibody completely ablated K. pneumoniae-induced liver injury. This
      reduction in liver injury failed to translate into an improved survival rate,
      because mice died of the infection as late as 10 days after infection. Bacterial
      clearance after neutralization of TNF-alpha was significantly impaired at later
      time points during infection. Diminished production of liver-associated cytokines
      and chemokines correlated with impaired bacterial clearance, which suggests that
      antibacterial immune responses were dampened. These data indicate that the
      antibacterial host response is dysregulated in mice lacking TNFR1 or TNF-alpha
      bioactivity.

PMID- 15983904
TI  - Comparative postautotomy tail activity in six Mediterranean lacertid lizard
      species.
AB  - Tail autotomy, the self-induced tail separation from the body, is a common and
      effective antipredator mechanism in lizards. In this study, we examine the muscle
      energetics of tail shedding in six lacertid lizard species (Podarcis erhardii,
      Podarcis peloponnesiaca, Podarcis muralis, Podarcis gaigeae, Podarcis milensis,
      and Lacerta graeca) from the northeast Mediterranean region. Very long periods of
      postautotomy tail movement were demonstrated for all species (range=6-8 min), and
      differences among species were not statistically significant. Postautotomy tail
      movement, powered by anaerobic muscle activity, resulted in a strong increase in
      lactate concentrations and a concomitant depletion of muscle glycogen of
      exhausted tails relative to resting tails. No significant differences were found
      in either lactate or glycogen concentrations among the species examined. Duration
      of movement was negatively correlated with final lactate concentrations. The lack
      of differentiation in postautotomy energetic physiology in this group of species
      that have evolved under very different predation environments indicates that
      postautotomy muscle metabolism involves an overall conservative suite of
      characters.

PMID- 15983905
TI  - A potentially significant interaction between efavirenz and phenytoin: a case
      report and review of the literature.
AB  - Although it has not been demonstrated yet, phenytoin is expected to reduce
      efavirenz exposure through coinduction of cytochrome P450 (CYP) 3A4 and CYP2B6.
      Conversely, efavirenz has been shown in vitro to inhibit the enzymes responsible
      for phenytoin metabolism, CYP2C9 and CYP2C19. We report a case in which a
      potential bidirectional drug interaction between phenytoin and efavirenz resulted
      in lower-than-expected efavirenz concentrations and elevated phenytoin levels.
      Therapeutic drug monitoring was used in this case to ensure adequate efavirenz
      exposure.

PMID- 15983906
TI  - Viral response to antiretroviral therapy in a patient coinfected with HIV type 1
      and type 2.
AB  - Clinical experience with the treatment of human immunodeficiency virus (HIV) type
      2 (HIV-2) infection is limited, and even more scarce is information on therapy
      for patients coinfected with HIV type 1 (HIV-1) and HIV-2. Here, we describe the
      outcome for a coinfected patient in whom infection with both viruses was
      successfully controlled at the start of antiretroviral therapy, but for whom HIV
      2 infection escaped control after a treatment simplification change while HIV-1
      remained undetectable.

PMID- 15983907
TI  - Upper respiratory tract involvement in the course of diffuse infiltrative
      lymphocytosis syndrome in HIV-1-infected patients: report of 2 cases.
AB  - Diffuse infiltrative lymphocytosis syndrome (DILS) in patients with human
      immunodeficiency virus (HIV) infection is characterized by persistent CD8(+)
      lymphocytosis with visceral lymphocytic infiltration. DILS induces a large
      spectrum of clinical features. We describe 2 HIV-infected patients with upper
      respiratory tract involvement that occurred during the course of DILS.

PMID- 15983908
TI  - Antimicrobial resistance among Streptococcus pneumoniae in the United States:
      have we begun to turn the corner on resistance to certain antimicrobial classes?
AB  - BACKGROUND: Antimicrobial resistance has emerged as a major problem in
      Streptococcus pneumoniae in the United States during the past 15 years. This
      study was undertaken to elucidate the current scope and magnitude of this problem
      in the United States and to assess resistance trends since 1994-1995. METHODS: A
      total of 1817 S. pneumoniae isolates obtained from patients with community
      acquired respiratory tract infections in 44 US medical centers were characterized
      during the winter of 2002-2003. The activity of 27 antimicrobial agents was
      assessed. In addition, selected isolates were examined for the presence of
      mutations in the quinolone-resistance determining regions (QRDRs) of parC and
      gyrA that resulted in diminished fluoroquinolone activity. The results of this
      survey were compared with the results of 4 previous surveys conducted in a
      similar manner since 1994-1995. RESULTS: Overall rates of resistance (defined as
      the rate of intermediate resistance plus the rate of resistance) were as follows:
      penicillin, 34.2%; ceftriaxone, 6.9%; erythromycin, 29.5%; clindamycin, 9.4%;
      tetracycline, 16.2%; and trimethoprim-sulfamethoxazole (TMP-SMX), 31.9%. No
      resistance was observed with vancomycin, linezolid, or telithromycin; 22.2% of
      isolates were multidrug resistant; 2.3% of isolates had ciprofloxacin MICs of
      >or=4.0 microg/mL. It was estimated that 21.9% of the isolates in this national
      collection had mutations in the QRDRs of parC and/or gyrA, with parC only
      mutations occurring most often (in 21% of all isolates). Trend analysis since
      1994-1995 indicated that rates of resistance to beta -lactams, macrolides,
      tetracyclines, TMP-SMX, and multiple drugs have either plateaued or have begun to
      decrease. Conversely, fluoroquinolone resistance among S. pneumoniae is becoming
      more prevalent. CONCLUSION: It appears that, as fluoroquinolone resistance
      emerges among S. pneumoniae in the United States, resistance to other
      antimicrobial classes is becoming less common.

PMID- 15983909
TI  - Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam
      monotherapy on the emergence of antimicrobial resistance: a meta-analysis of
      randomized, controlled trials.
AB  - BACKGROUND: The addition of an aminoglycoside to a beta -lactam therapy regimen
      has been suggested to have a beneficial effect in delaying or preventing the
      development of antimicrobial resistance. We studied the effect of aminoglycoside/
      beta -lactam combination therapy versus beta-lactam monotherapy on the emergence
      of resistance. METHODS: We performed a meta-analysis of randomized, controlled
      trials (RCTs) that compared aminoglycoside/ beta-lactam combination therapy with
      beta-lactam monotherapy and that reported data regarding the emergence of
      resistance (primary outcome) and/or development of superinfection, treatment
      failure, treatment failure attributable to emergence of resistance, treatment
      failure attributable to superinfection, all-cause mortality during treatment, and
      mortality due to infection. Data for this meta-analysis were identified from the
      PubMed database, Current Contents database, Cochrane central register of
      controlled trials, and references in relevant articles. RESULTS: A total of 8
      RCTs were included in the analysis. Beta -lactam monotherapy was not associated
      with a greater emergence of resistance than was the aminoglycoside/ beta-lactam
      combination (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56-1.47).
      Actually, beta -lactam monotherapy was associated with fewer superinfections (OR,
      0.62; 95% CI, 0.42-0.93) and fewer treatment failures (OR, 0.62; 95% CI, 0.38
      1.01). Rates of treatment failure attributable to emergence of resistance (OR,
      3.09; 95% CI, 0.75-12.82), treatment failure attributable to superinfection (OR,
      0.60; 95% CI, 0.33-1.10), all-cause mortality during treatment (OR, 0.70; 95% CI,
      0.40-1.25), and mortality due to infection (OR, 0.74; 95% CI, 0.46-1.21) did not
      differ significantly between the 2 regimens. CONCLUSIONS: Compared with beta
      lactam monotherapy, the aminoglycoside/ beta-lactam combination was not
      associated with a beneficial effect on the development of antimicrobial
      resistance among initially antimicrobial-susceptible isolates.

PMID- 15983910
TI  - Risk factors for colonization with methicillin-resistant Staphylococcus aureus
      (MRSA) in patients admitted to an urban hospital: emergence of community
      associated MRSA nasal carriage.
AB  - BACKGROUND: Surveillance cultures performed at hospital admission have been
      recommended to identify patients colonized with methicillin-resistant
      Staphylococcus aureus (MRSA) but require substantial resources. We determined the
      prevalence of and risk factors for MRSA colonization at the time of hospital
      admission among patients cared for at a public urban hospital. METHODS: Anterior
      nares cultures were obtained within 48 h after admission during a 1-month period.
      A case-control study and molecular typing studies were performed. RESULTS: A
      total of 53 (7.3%) of 726 patients had a nares culture positive for MRSA, and 119
      (16.4%) had a nares culture that was positive for methicillin-susceptible S.
      aureus. In multivariate analysis, risk factors for MRSA colonization included
      antibiotic use within 3 months before admission (odds ratio [OR], 2.5; 95%
      confidence interval [CI], 1.2-5.0), hospitalization during the past 12 months
      (OR, 4.0; 95% CI, 2.0-8.2), diagnosis of skin or soft-tissue infection at
      admission (OR, 3.4; 95% CI, 1.5-7.9), and HIV infection. A total of 47 (89%) of
      53 case patients colonized with MRSA had at least 1 of these independent risk
      factors, in contrast to 343 (51%) of 673 control patients (OR, 7.5; 95% CI, 3.2 
      17.9). Molecular typing demonstrated that 16 (30%) of 53 MRSA nares isolates
      (2.2% of the 726 isolates) belonged to the USA300 community-associated MRSA (CA
      MRSA) genotype. CONCLUSION: The prevalence of MRSA colonization at the time of
      patient admission was high (>7%). Limiting surveillance cultures to patients with
      >or=1 of the identified risk factors may allow for targeted screening. The
      emergence of CA-MRSA colonization represents a new, unrecognized reservoir of
      MRSA within hospitals, potentially increasing the risk for horizontal
      transmission.

PMID- 15983911
TI  - Prevention of health care-associated methicillin-resistant Staphylococcus aureus
      infections: adapting to a changing epidemiology.

PMID- 15983912
TI  - Recurrent exposure to Histoplasma capsulatum in modern air-conditioned buildings.
AB  - BACKGROUND: Between 1989 and 1996, an epidemic of histoplasmosis occurred on a
      medical school campus. There had been numerous construction projects on the
      campus that involved previously wooded land and were adjacent to a large bird
      sanctuary. METHODS: We investigated the epidemic with active surveillance to
      detect cases, a histoplasmin skin-test survey, inspection of the air-filtration
      systems of the involved buildings, and cultures of soil samples. The
      investigation also included a simulation of entry into air-intakes of the
      buildings from spore sources by means of a wind-tunnel analysis of a model of the
      campus that used inert gas. After control procedures were instituted, sentinel
      population groups had follow-up with yearly serological tests. RESULTS: From 1989
      through 1996, there were 29 cases of histoplasmosis that occurred among school
      employees. All cases with a defined onset began during periods of ongoing campus
      construction. Positivity rates for histoplasmin skin testing were higher among on
      campus personnel (47%) than among off-campus employee control subjects (28%)
      (P<.001); the rates were highest in employees who worked on the upper floors of 2
      research buildings. The air-handling units on the roofs of these buildings were
      not designed to exclude Histoplasma spores. The wind-tunnel experiment indicated
      that spores aerosolized in the bird sanctuary were not taken into campus
      buildings. CONCLUSIONS: The major sources of employee exposure to H. capsulatum
      spores were the construction sites. Low-level, recurrent exposures occurred over
      several years inside modern research buildings. This phenomenon, which has not
      been previously described, may play a role in the epidemiology of spore
      transmitted diseases in urban settings.

PMID- 15983913
TI  - Hepatitis C virus infection among prisoners in the California state correctional
      system.
AB  - BACKGROUND: Incarcerated populations are at high risk for hepatitis C virus (HCV)
      infection, yet prisoners are not routinely screened or treated for HCV infection.
      Understanding the risk factors of HCV infection among prisoners could help
      improve HCV interventions. METHODS: Prevalence and risk of HCV infection among
      469 prisoners entering California State correctional facilities were assessed
      using HCV antibody screening, HCV RNA measurement, and structured interviews.
      Multivariate logistic regression analysis was used to identify independent
      correlates of HCV infection. RESULTS: The prevalence of HCV infection was 34.3%
      overall (95% confidence interval [CI], 30%-38%) and was 65.7% among those with a
      history of injection drug use (IDU), compared with 10.2% among those with no
      history of IDU (odds ratio [OR], 17.24; 95% CI, 10.52-28.25). Significant
      differences in HCV antibody positivity were found in association with age at
      first detention but not with the nature of the crime. Independent correlates of
      HCV infection included age, history of IDU, cumulative time of incarceration,
      biological sex (OR for females subjects compared with males subjects, 0.35; 95%
      CI, 0.13-0.96), and a history of having sex with a male IDU (OR, 4.42; 95% CI,
      1.46-13.37). We identified significant differences in risk factors between male
      and female subjects--notably, that the risk of HCV infection was significantly
      elevated among female non-IDUs who reported having sexual partners with a history
      of IDU. Among non-IDUs, correlates of HCV infection included history of receipt
      of blood products and cumulative years of incarceration. CONCLUSIONS: HCV
      infection is pervasive among the California prison population, including
      prisoners who are non-IDUs and women with high-risk sexual behavior. These
      results should promote consideration of routine HCV antibody screening and
      behavioral interventions among incarcerated men and women.

PMID- 15983914
TI  - Bacteriological outcome after valve surgery for active infective endocarditis:
      implications for duration of treatment after surgery.
AB  - BACKGROUND: There has been no systematic evaluation of outcome after surgery for
      infective endocarditis with respect to duration of antibiotic treatment. METHODS:
      We performed a retrospective chart review of episodes of valve surgery for active
      infective endocarditis at Green Lane Hospital (Auckland, New Zealand) for 1963
      1999. We recorded the duration of antibiotic treatment before and after valve
      surgery; the extent of infection at operation; Gram stain, culture, and
      histopathological testing results for valve samples; and the bacteriological
      outcome after surgery. The primary outcome measure was relapse, defined as
      endocarditis due to the same species within 1 year after surgery. RESULTS: For
      the 358 patients in our study, the median duration of follow-up was 4.8 years.
      Thirty-two patients (9%) had 36 subsequent episodes of endocarditis. Relapse
      occurred after 3 (0.8%) of the operations (95% CI, 0.2%-2.0%). Relapse of
      infection was unrelated to the duration of antibiotic treatment before or after
      surgery, positive valve culture results, positive Gram stain results, or
      perivalvular infection. Since 1994, we have reduced the duration of antibiotic
      treatment by approximately 7 days for those with positive valve culture results
      and by approximately 14 days for those with negative valve culture results,
      without any increase in the number of relapses. CONCLUSIONS: Relapse is an
      uncommon event following surgery for endocarditis. Commonly suggested indications
      for prolonging postoperative treatment are not associated with higher relapse
      rates, and their relevance is debatable. We conclude that it is unnecessary to
      continue treatment for patients with negative valve culture results for an
      arbitrary 4-6-week period after surgery. Two weeks of treatment appears to be
      sufficient, and, for those operated on near the end of the standard period of
      treatment, simply completing the planned course should suffice.

PMID- 15983915
TI  - Investigation of postoperative allograft-associated infections in patients who
      underwent musculoskeletal allograft implantation.
AB  - BACKGROUND: The rate at which allografts are used in surgical procedures has
      doubled in the United States during the past decade. In 2002, one outpatient
      surgical center (SC-X) identified a cluster of surgical site infections (SSIs)
      after anterior cruciate ligament reconstructive surgery (ACLRS). Therefore, we
      conducted an investigation to determine the extent of the outbreak and to
      identify risk factors. METHODS: Our investigation included retrospective cohort
      and observational studies. A case patient was defined as any patient who acquired
      a SSI after undergoing ACLRS at SC-X between February 2000 and June 2002 (the
      study period). Data collected included demographic characteristics, clinical
      information, and graft details, such as processing method (i.e., aseptic or
      sterile). RESULTS: Of 331 patients who underwent ACLRS during the study period,
      11 (3.3%) met the case definition. All infections occurred at the tibial fixation
      site of the graft and involved 8 different microorganisms; the median time to a
      positive culture result was 55 days after ACLRS. The infection rate for patients
      who received aseptically processed allografts was 4.4% (11 of 250 patients),
      compared with 0% (0 of 81) for patients who received autografts or sterile
      allografts (P=.07). Use of a supplementary staple for tibial fixation, compared
      with other fixation methods that did not involve such staples, increased the risk
      of infection 10-fold in univariate analysis (relative risk [RR], 10.0; 95%
      confidence interval [CI], 3.0-32.9) and 9-fold when controlling for tissue
      processing method (RR, 9.0; 95% CI, 2.8-28.8). CONCLUSIONS: The use of sterile
      allograft tissue appears to be associated with a significant reduction in the
      risk of postoperative infection, particularly in the presence of adjunctive
      fixation. Larger clinical studies are necessary to confirm this observation.

PMID- 15983916
TI  - Reconsidering adjuvant immunotherapy for tuberculosis.
AB  - BACKGROUND: Shortened regimens for treatment of pulmonary tuberculosis (TB) are
      urgently needed to facilitate its global eradication. Prolonged treatment is
      presently required to prevent relapse, which is thought to arise from persisting
      foci of semidormant infection contained within granulomas. METHODS: The medical
      literature was reviewed to identify clinical trials of adjuvant TB immunotherapy,
      as well as other studies of the relationship between immune status and TB relapse
      or reactivation. RESULTS: Four studies of therapeutic interferon indicated its
      inability to effectively augment the mycobactericidal capacity of lung
      macrophages. One randomized, placebo-controlled trial of therapeutic interleukin
      2 found that it delayed the microbiologic response to treatment, whereas 2
      controlled trials of anti-tumor necrosis factor (TNF) therapies (high-dose
      prednisolone and etanercept [a soluble TNF receptor]) found that these
      interventions significantly accelerated the response to treatment. Four
      retrospective studies were identified in which the response to TB therapy was
      accelerated and/or the relapse risk was reduced in persons with human
      immunodeficiency virus coinfection; one study reported that immune reconstitution
      syndrome due to use of antiretroviral therapy was associated with increased risk
      of relapse. Several studies indicated that granulomas may be efficiently targeted
      and disrupted by the anti-TNF antibody infliximab, apparently because of its
      ability to bind to cell-surface TNF and to induce apoptosis in TNF-expressing
      cells. CONCLUSIONS: These findings support the hypothesis that the granulomatous
      host response to TB may paradoxically protect sequestered mycobacteria from
      administered anti-TB therapy and that treatment may be improved by therapeutic
      disruption of granulomas. Clinical trials to test this hypothesis are warranted.

PMID- 15983917
TI  - Control of vancomycin-resistant enterococci: one size fits all?
AB  - Infection caused by vancomycin-resistant enterococci (VRE) is associated with
      high morbidity and mortality rates; it poses a serious threat, in particular, to
      immunosuppressed patients. It generates high costs and challenges infection
      control programs. Here, we look at the insights that mathematical models offer
      into the epidemiology of VRE colonization and infection, the potential benefits
      of various infection-control interventions, and the possibility of designing a
      tailored approach to controlling VRE. Models show that epidemics of VRE infection
      in diverse institutions may differ in the relative contributions of cross
      transmission and the influx of new cases, as well as in the various mechanisms of
      local transmission. They also highlight the phenomenon of decreasing returns
      associated with many interventions and, hence, the need to identify the most
      important routes of transmission, to break the weakest links in the chain of
      transmission, and to contain the influx of cases of VRE infection. These
      observations also provide insights into the management of infection with other
      antibiotic-resistant nosocomial pathogens.

PMID- 15983918
TI  - Efficacy of antiretroviral therapy programs in resource-poor settings: a meta
      analysis of the published literature.
AB  - BACKGROUND: Despite the advent of effective combination antiretroviral drug
      therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection,
      many doubt the feasibility of ART treatment programs in resource-poor settings.
      We performed a meta-analysis of the efficacy of ART programs in the developing
      world. We searched the Medline database with the index terms "HIV,"
      "antiretroviral therapy," "CD4 count," "viral load," "experience," and
      "outcomes." A total of 201 abstracts were reviewed, and 25 articles were selected
      for detailed review. Ten observational studies with details on patient outcomes
      were ultimately included in the analysis. METHODS: Three readers independently
      extracted data from the articles. The details recorded included patient
      demographic characteristics, baseline CD4 cell counts, baseline HIV RNA viral
      loads, ART histories, outcomes, and timing of the outcome measure. RESULTS: The
      proportion of subjects with an undetectable HIV viral load provided the measure
      of treatment efficacy. A random-effects model weighted the proportion of patients
      with undetectable viral load at various time points during ART. The proportion
      was 0.697 (95% CI, 0.582-0.812) at month 6 and 0.573 (95% CI, 0.432-0.715) at
      month 12 of ART. The provision of medications free of charge to the patient was
      associated with a 29%-31% higher probability of having an undetectable viral load
      at months 6 and 12 than was the requirement that patients pay part or all of the
      cost of therapy. CONCLUSIONS: ART treatment programs in resource-poor settings
      have efficacy rates similar to those reported for developed countries. The
      provision of medications free of charge to the patient is associated with a
      significantly increased probability of virologic suppression at months 6 and 12
      of ART.

PMID- 15983919
TI  - Outcomes for patients receiving antiretroviral therapy in the developing world
      appear to be not much different from those in the developed world.

PMID- 15983920
TI  - Antiretroviral recommendations may influence the rate of transmission of drug
      resistant HIV type 1.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) treatment guidelines have evolved,
      shifting from more-aggressive to more-conservative approaches. The potential
      impact of these shifts on the transmission of drug-resistant virus is unknown.
      METHODS: Drug-resistance genotypes were examined in all consecutive patients with
      recent HIV type 1 (HIV-1) seroconversion (hereafter, "HIV-1 seroconverters") seen
      at 10 Spanish hospitals since 1997. During the same period, the proportion of
      patients with chronic HIV-1 infection having undetectable viremia was examined,
      to estimate the extent and effectiveness of antiretroviral therapy. RESULTS: A
      total of 141 recent HIV-1 seroconverters were identified, 67.4% of whom were men
      who have sex with men. The rate of primary drug-resistance mutations, by year of
      infection, was 33.3% for 1997, 29.4% for 1998, 20% for 1999, 14.3% for 2000, 3.4%
      for 2001, 15.4% for 2002, and 10.9% for 2003. On the other hand, the proportion
      of 8388 persons with chronic HIV-1 carriage who had an undetectable virus load
      was 33.4% for 1997, 34.6% for 1998, 39.7% for 1999, 47.5% for 2000, 52.9% for
      2001, 39.7% for 2002, and 58.1% for 2003. A significant inverse correlation
      between transmission of drug-resistant HIV-1 and undetectable virus load was
      found (r=-0.955, by Spearman's test; P=.001). The lowest rate of transmission of
      drug-resistant HIV-1 was seen in 2001, when relatively "aggressive" treatment
      guidelines were used. Transmission of drug-resistant HIV-1 increased in 2002, in
      parallel with a reduction in the number of patients with chronic HIV-1 carriage
      and undetectable virus load, reflecting the popularity of drug holidays or
      treatment interruptions. CONCLUSION: The rate of drug resistance in recent HIV-1
      seroconverters inversely correlates with the proportion of chronically HIV-1
      infected individuals who have undetectable virus loads in the same region, which
      indirectly reflects antiretroviral treatment rules at any given time.

PMID- 15983921
TI  - HIV treatment decisions and transmitted drug resistance.

PMID- 15983922
TI  - Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1
      infection.
AB  - BACKGROUND: Maximum suppression of virus replication is often not achievable for
      persons infected with multidrug-resistant human immunodeficiency virus type 1
      (HIV-1). Available data suggest that lamivudine contributes to partial viral
      suppression, despite the presence of M184V mutations and high-level phenotypic
      lamivudine resistance. METHODS: Selective lamivudine withdrawal was studied in 6
      subjects who had incomplete viral suppression during antiretroviral treatment for
      multidrug-resistant HIV-1 infection. RESULTS: Plasma levels of HIV-1 RNA
      increased to 0.5 log(10) copies/mL above baseline 6 weeks after the withdrawal of
      lamivudine treatment (P=.04), even though reversion of lamivudine resistance was
      not yet detected. Early increases in plasma levels of HIV-1 RNA after lamivudine
      withdrawal were associated with the presence of the T215Y/F mutation and broad
      phenotypic resistance to nucleoside reverse-transcriptase inhibitors at baseline.
      Genotypic and phenotypic reversion of lamivudine resistance was detected in 4
      subjects 8-14 weeks after withdrawal of lamivudine therapy. The duration of
      lamivudine withdrawal ranged from 8 to 22 weeks; all subjects resumed lamivudine
      treatment. Plasma levels of HIV-1 RNA were 0.6 log(10) copies/mL above baseline
      (P=.03) when lamivudine therapy was resumed. After the resumption of lamivudine
      treatment, plasma HIV RNA levels decreased to baseline levels in 3 subjects but
      remained elevated in 3 subjects who had evolution of increased antiretroviral
      drug resistance during the period of lamivudine withdrawal. Safety concerns
      raised by this latter finding led to permanent closure of the study. CONCLUSIONS:
      In select cases of multidrug-resistant HIV-1 infection, lamivudine contributes to
      suppression of HIV-1 replication, despite the presence of M184V mutations and
      lamivudine resistance.

PMID- 15983923
TI  - HIV-1 proteases from drug-naive West African patients are differentially less
      susceptible to protease inhibitors.
AB  - BACKGROUND: Now that highly active antiretroviral therapy (HAART) is being
      initiated on a large scale in West Africa, it remains controversial whether
      protease inhibitors (PIs), originally designed and tested against human
      immunodeficiency virus type 1 (HIV-1) subtype B, are equally effective against
      the non-B subtypes that are prevalent in West African countries. In this study,
      we investigated whether Ghanaian HIV-1 isolates, as representatives of West
      African isolates, are susceptible to PIs. METHODS: We first generated an HIV-1
      protease cassette vector proviral DNA carrying a luciferase gene, which allows
      patient-derived HIV-1 proteases to be inserted and to be subjected to both
      genotypic and phenotypic assays. HIV-1 protease genes derived from 39 treatment
      naive Ghanaian patients were used in this experiment as representatives of West
      African strains. The cloned patient-derived HIV-1 protease genes were first
      sequenced and then genetically compared. Phenotypic analysis was performed with
      Ghanaian HIV-1 protease-chimeric viruses in the presence of 6 different PIs.
      Structural models of HIV-1 protease homodimers were constructed by the molecular
      modeling software. RESULTS: Genetic analysis of cloned patient-derived HIV-1
      protease genes indicated that most of the Ghanaian HIV-1 proteases are placed as
      subtype CRF02_AG strains, which are phylogenetically distant from subtype B
      strains, and that Ghanaian HIV-1 proteases do not harbor known major mutations
      influencing drug resistance but commonly carry 2-3 minor mutations. Phenotypic
      analysis performed with HIV-1 protease-recombinant viruses in the presence of 6
      different PIs revealed that Ghanaian HIV-1 proteases are differentially less
      susceptible to the PIs. In support of this finding of differential
      susceptibility, structural analysis showed a significant distortion of
      nelfinavir, but not of amprenavir, in the Ghanaian protease pocket, suggesting
      nelfinavir might be less insertable into the Ghanaian protease than into the
      protease of subtype B. CONCLUSIONS: These findings provide implications for the
      combination of PIs during the introduction of HAART into West Africa.

PMID- 15983924
TI  - Among the devils in the details are protease sequence, susceptibility, and
      structure in CRF02_AG viruses.

PMID- 15983925
TI  - Community permission for medical research in developing countries.
AB  - The realization of the need for community consent, or more accurately community
      permission, for research has occurred relatively recently. Practical experience
      with it is scarce. This article describes the Malian experience at a malaria
      vaccine study site. We describe a process that we used to obtain community
      permission. The process had 6 steps: (1) a study of the community, (2) an
      introductory meeting with leaders, (3) formal meetings with leaders, (4) personal
      visits with leaders, (5) meetings with traditional health practitioners, and (6)
      recognition that obtaining permission is a dynamic process. We discuss
      documentation of community permission for research and outline the reasons why
      the community-level process we used was practically necessary and ethically
      appropriate. Far from competing with the individual informed consent process, the
      process of obtaining community permission both initiated and facilitated the
      process of disclosure for individual informed consent.

PMID- 15983926
TI  - Rhinovirus outbreak in a long term care facility for elderly persons associated
      with unusually high mortality.
AB  - During a 6-week period in 2003, 56 residents and 26 staff developed respiratory
      illness in a long-term facility; 12 residents died. Seven of 13 respiratory
      specimens were culture-positive for rhinovirus; 6 of the isolates were serotype
      82. In elderly populations, severe illness may be associated with organisms
      typically considered to be "benign," such as rhinovirus.

PMID- 15983927
TI  - Uncommon(ly considered) manifestations of infection with rhinovirus, agent of the
      common cold.

PMID- 15983928
TI  - Value of screening and isolation for control of methicillin-resistant
      Staphylococcus aureus.

PMID- 15983929
TI  - Has methicillin-resistant Staphylococcus aureus stopped spreading in intensive
      care units?

PMID- 15983932
TI  - How late after injection can a tuberculin skin test be interpreted?

PMID- 15983933
TI  - Routine vaccination of HIV-infected patients against hepatitis A: should we
      discriminate before vaccination according to ethnicity?

PMID- 15983934
TI  - Influenza infections after hematopoietic stem cell transplantation.

PMID- 15983935
TI  - Klebsiella liver abscess: a coast-to-coast phenomenon.

PMID- 15983936
TI  - Diagnosis and treatment of fungal endophthalmitis: a reassessment.

PMID- 15983938
TI  - Introduction: management of target localization uncertainties in external-beam
      therapy.

PMID- 15983939
TI  - Target definition in prostate, head, and neck.
AB  - Target definition is a major source of errors in both prostate and head and neck
      external-beam radiation treatment. Delineation errors remain constant during the
      course of radiation and therefore have a large impact on the dose to the tumor.
      Major sources of delineation variation are visibility of the target including its
      extensions, disagreement on the target extension, and interpretation or lack of
      delineation protocols. The visibility of the target can be greatly improved with
      the use of multimodality imaging. Both in the head and neck and the prostate,
      computed tomography (CT)-magnetic resonance imaging coregistration decreases the
      target volume and its variability. CT-positron emission tomography delineation is
      promising for delineation in head and neck cancer. Despite the better visibility,
      a different interpretation of the target extension remains a major source of
      error. The use of coregistration of CT with a second modality, together with
      improved guidelines for delineation and an online anatomical atlas, increases
      agreement between observers in prostate, lung, and nasopharynx tumors.
      Delineation errors should not be treated differently from other geometrical
      errors. Similar margin recipes for the correction of setup errors and organ
      motion should be adapted to incorporate the effect of delineation errors. A
      calculation of a 3-dimensional clinical target volume-planning target volume
      margin incorporating delineation errors for the head and neck is around 6.1 to
      9.7 mm. Given the good local control of IMRT with smaller margins and smaller
      pathological specimens, it is likely that the delineated CTV frequently
      overestimates the actual volume.

PMID- 15983940
TI  - Target definition in the thorax and central nervous system.
AB  - It is the aim of conformal radiotherapy to restrict the high-dose region to the
      target volume as much as possible, thereby sparing the neighboring healthy
      tissues. However, to increase the therapeutic range, smaller margins tend to be
      used. This reduction of safety margins enhances the risk of unsuitable dosage
      because of mistaken target definition. Central nervous system (CNS) and lung
      cancers constitute sites that are particularly difficult to irradiate combining a
      large number of conceptual difficulties, allowing them to be considered as 2
      particularly interesting study models. Imaging occupies an increasingly important
      place in these 2 types of tumors, especially with the development of new
      radiotherapy techniques. CNS and lung cancers represent an example of
      clinicopathological correlations. More specifically, CNS cancers represent an
      excellent model for estimation of new 3-dimensional navigational systems. For
      lung cancer, there is a combination of ballistic difficulties because of
      respiratory motion, the number and low tolerance of neighboring organs, and
      dosimetric difficulties because of the presence of inhomogeneities. This article
      reviews the main currently accepted criteria of choice justifying the size of
      gross tumor volume and clinical target volume margins for lung and CNS cancers.

PMID- 15983941
TI  - Clinical use of electronic portal imaging.
AB  - Accurate and routine target localization is necessary for successful outcome in
      radiation therapy treatments. Electronic portal imaging devices (EPIDs) provide
      an advanced tool with digital technology to improve target localization and
      maintain clinical efficiency. EPIDs are ubiquitous in the radiation therapy
      clinic, and they provide a powerful and flexible tool to collect and process data
      in a quantitative manner to improve treatment accuracy for virtually any
      treatment site. This manuscript provides an overview of the clinical
      implementation process for effective use of EPIDs. It continues with a review of
      correction strategies and finally highlights numerous examples of effective
      clinical application of EPID.

PMID- 15983942
TI  - Computed tomography guided management of interfractional patient variation.
AB  - Interfractional patient variation occurs regularly and considerably during the
      radiotherapy course. Consequently, a generic but large planning target margin has
      to be applied when patient treatment plan design based on a single pre-treatment
      computed tomography scan is used to guide multifraction radiation treatment,
      which creates a major limiting factor for radiotherapy improvement. Planning
      target margins can be significantly reduced using multiple (or 4-dimensional)
      image feedback management in the routine treatment process. The most effective
      method in multiple-image feedback management of radiotherapy is the adaptive
      control methodology. The adaptive radiotherapy technique aims to customize each
      patient's treatment plan to patient-specific variation by evaluating and
      characterizing the systematic and random variations through image feedback and
      including them in adaptive planning. Adaptive radiotherapy will become a new
      treatment standard, in which a predesigned adaptive treatment strategy, including
      the schedules of imaging and replanning, will eventually replace the predesigned
      treatment plan in the routine clinical practice.

PMID- 15983943
TI  - Ultrasound-based localization.
AB  - Ultrasound is a noninvasive, relatively easy, rapid, and real-time imaging
      technique for organ targeting for radiotherapy. Its application has been
      developed to a greater extent in prostate cancer than in other sites in which it
      has been shown to improve the accuracy of daily treatment delivery. With the move
      toward dose escalation and the need to maximally spare the adjacent critical
      structures through more conformal therapy and smaller field margins, an
      innovative technique for accurate and reproducible tumor targeting is mandatory.
      Basic ultrasound principles and organ location lend themselves well to the
      application of this modality in prostate cancer. Promising results using daily
      ultrasound-guided B-mode acquisition and targeting for patients with upper
      abdominal tumors suggest an area for additional trials and study. For breast
      cancer radiotherapy, ultrasound serves to define involved primary and nodal
      sites, especially in patients in whom surgical evaluation will not be the first
      therapeutic step.

PMID- 15983944
TI  - Optically guided patient positioning techniques.
AB  - Optical tracking determines an object's position by measuring light either
      emitted or reflected from the object. The hallmark of optical tracking systems is
      their high spatial resolution and measurement in real time; such systems can
      resolve the position of a point source within a fraction of a millimeter and
      report at a rate of 10 Hz or faster. Several systems have been developed for
      radiation therapy, all of which track infrared markers attached to the patient's
      external surface. The positions of the optical markers relative to the target
      volume, together with the desired marker positions relative to treatment
      isocenter, are determined during computed tomography simulation. In the treatment
      room, the real marker positions are measured relative to isocenter; rigid-body
      mathematics then determine marker displacements from their desired positions and
      hence target displacement from isocenter. Real-time feedback allows one to
      correct the patient's position. The first systems were used for intracranial
      stereotaxis radiotherapy; rigid arrays of optical markers were attached to the
      patient via a biteplate linkage. Subsequent systems for extracranial radiotherapy
      tracked external markers to determine patient position and/or gate the radiation
      beam based on patient motion. Lastly, optical tracking has been integrated with
      ultrasound or stereoscopic x-ray imaging to determine the position of internal
      anatomy targets relative to isocenter.

PMID- 15983945
TI  - Extracranial stereotactic radiation delivery.
AB  - Extracranial stereotactic radiation delivery, also known as stereotactic body
      radiation therapy (SBRT), involves delivering very potent doses of radiation to
      well-demarcated tumors in the neck, spine, chest, abdomen, and pelvis. Beyond
      just stereotactic targeting, it represents a formalism of treatment planning and
      conduct that facilitates the delivery of the most potent dose fractionation
      schedules ever considered in the field of radiation oncology. In doing so, it
      uses the most modern technologies to simultaneously hit the target and avoid
      normal innocent tissues. Clinical results already show that SBRT constitutes a
      new paradigm in cancer treatment that deserves careful implementation and
      assessment for the improvement in patient outcomes.

PMID- 15983946
TI  - Emergent technologies for 3-dimensional image-guided radiation delivery.
AB  - Radiation therapy targeting is being refined to formally accommodate location of
      gross disease, microscopic extension, and geometric uncertainties in the delivery
      process. This formalization allows the disciplines in radiation oncology practice
      to work collaboratively to assure target coverage while attempting to minimize
      toxicity in adjacent normal structures. There is a growing expectation that the
      precise and accurate placement of radiation dose is well in hand. The development
      of volumetric imaging systems integrated with the medical linear accelerator for
      the specific purpose of guiding therapy will permit localization and targeting of
      soft-tissue structures at the time of treatment. In this review, the context for
      development of image-guided radiation therapy is discussed, and the growing
      expectation of volumetric guidance is portrayed through the various technologies
      currently being explored in the radiation therapy community.

PMID- 15983947
TI  - Quiz page. Secondary hypertension with contralateral pheochromocytoma and
      aldosteronoma.

PMID- 15983949
TI  - Minimal change nephrotic syndrome with stiff-person syndrome: is there a link?
AB  - Stiff-person syndrome is a rare, likely immune-mediated neurological disorder
      characterized by painful spasms and progressive symmetric rigidity of the axial
      and proximal limb muscles. Rigidity of truncal muscles and continuous contraction
      of the agonist and antagonist muscles caused by involuntary motor-unit firing at
      rest are the hallmarks of stiff-person syndrome. Immunosuppressive therapy has
      induced remission in patients with stiff-person syndrome. We report a patient
      with stiff-person syndrome with minimal change nephrotic syndrome (MCNS). The
      pathophysiologic states of stiff-person syndrome and MCNS are unclear. T-Cell
      dependent mechanisms are highly suspected for the pathogenesis of both. The
      diagnosis of stiff-person syndrome was made on the basis of clinical and
      laboratory findings, and both MCNS and stiff-person syndrome resolved completely
      with immunosuppressive therapy. To our knowledge, this is the first case of stiff
      person syndrome in association with MCNS in the literature.

PMID- 15983950
TI  - Recurrent high anion gap metabolic acidosis secondary to 5-oxoproline
      (pyroglutamic acid).
AB  - High anion gap metabolic acidosis in adults is a severe metabolic disorder for
      which the primary organic acid usually is apparent by clinical history and
      standard laboratory testing. We report a case of recurrent high anion gap
      metabolic acidosis in a 48-year-old man who initially presented with anorexia and
      malaise. Physical examination was unrevealing. Arterial pH was 6.98, P co 2 was 5
      mm Hg, and chemistry tests showed a bicarbonate level of 3 mEq/L (3 mmol/L),
      anion gap of 32 mEq/L (32 mmol/L), and a negative toxicology screen result,
      except for an acetaminophen (paracetamol) level of 7.5 mug/mL. Metabolic acidosis
      resolved with administration of intravenous fluids. Subsequently, he experienced
      5 more episodes of high anion gap metabolic acidosis during an 8-month span.
      Methanol, ethylene glycol, acetone, ethanol, d -lactate, and hippuric acid
      screens were negative. Lactate levels were modestly elevated, and acetaminophen
      levels were elevated for 5 of 6 admissions. These episodes defied explanation
      until 3 urinary organic acid screens, obtained on separate admissions, showed
      striking elevations of 5-oxoproline levels. Inborn errors of metabolism in the
      gamma-glutamyl cycle causing recurrent 5-oxoprolinuria and high anion gap
      metabolic acidosis are rare, but well described in children. Recently, there have
      been several reports of apparent acquired 5-oxoprolinuria and high anion gap
      metabolic acidosis in adults in association with acetaminophen use. Acetaminophen
      may, in susceptible individuals, disrupt regulation of the gamma-glutamyl cycle
      and result in excessive 5-oxoproline production. Suspicion for 5-oxoproline
      associated high anion gap metabolic acidosis should be entertained when the cause
      of high anion gap metabolic acidosis remains poorly defined, the anion gap cannot
      be explained reasonably by measured organic acids, and there is concomitant
      acetaminophen use.

PMID- 15983951
TI  - Natriuretic peptides in ESRD.
AB  - Natriuretic peptides are involved in the regulation of volume homeostasis. Their
      levels generally are increased in the setting of volume expansion and act on
      multiple effector systems to cause vasodilation and natriuresis in an effort to
      return volume status back to normal. In patients with end-stage renal disease,
      the natriuretic capabilities of these peptides are limited. However, there has
      been much interest in the potential applicability of measurement of these
      peptides as a surrogate marker of volume status and in the determination of dry
      weight. Furthermore, atrial natriuretic peptide and brain natriuretic peptide can
      serve as markers of left ventricular dysfunction and may have utility in
      determining cardiac prognosis in patients on long-term dialysis therapy.

PMID- 15983952
TI  - Prevalence of family history of kidney disease and perception of risk for kidney
      disease: a population-based study.
AB  - BACKGROUND: A family history of kidney disease is associated with an increased
      risk for end-stage renal disease (ESRD). However, it is unclear whether blacks
      are more likely to have a family history of ESRD than other groups independently
      of kidney disease risk factors. Moreover, their risk perception for kidney
      disease is unknown. METHODS: The association of race with family history of ESRD
      and perception of risk for kidney disease was examined in a representative random
      sample of 402 Georgia residents who completed a telephone interview. Logistic
      regression analysis was used to derive adjusted odds ratios and 95% confidence
      intervals for the association between race and family history of ESRD,
      controlling for age, sex, education level, being a Georgia native, diabetes,
      hypertension, and personal history of kidney disease. A multinomial logit model
      was used to derive adjusted estimates for the association between race and
      perception of risk for kidney disease. RESULTS: Mean age was 43.2 years, 41.0% of
      respondents were men, 20.1% were black, 6.6% had diabetes, 21.4% had
      hypertension, 1.6% had a personal history of kidney disease, and 3.7% reported a
      family member with ESRD. Although blacks were more likely to report a family
      history of ESRD (odds ratio, 6.43; 95% confidence interval, 2.02 to 20.43), their
      perception of risk was not greater. CONCLUSION: Although blacks are approximately
      6 times as likely to report a family history of ESRD independently of a personal
      history of kidney disease, diabetes, or hypertension, they do not perceive
      themselves as more vulnerable for kidney disease.

PMID- 15983953
TI  - Management of hypertension in patients with CKD: differences between primary and
      tertiary care settings.
AB  - BACKGROUND: Although most patients with moderate chronic kidney disease (CKD) are
      managed exclusively in primary care (PC), no data on blood pressure (BP) control
      in this setting are available. We compared hypertension management in patients
      with CKD followed up in PC and nephrology tertiary care (TC). METHODS: We studied
      hypertensive patients with estimated glomerular filtration rates (eGFRs) of 15 to
      60 mL/min/1.73 m2 (0.25 to 1.00 mL/s) exclusively followed up for at least 1 year
      in PC (n = 259) or TC (n = 186). RESULTS: PC compared with TC patients were
      characterized by older age (73 +/- 10 versus 65 +/- 14 years; P < 0.0001),
      greater prevalences of previous cardiovascular events (59% versus 32%; P <
      0.0001) and diabetes (36% versus 23%; P = 0.005), and slightly greater eGFRs (37
      +/- 10 versus 34 +/- 11 mL/min/1.73 m2 ; P = 0.005). They showed higher BP levels
      (143 +/- 15/82 +/- 7 versus 136 +/- 18/78 +/- 11 mm Hg; P < 0.0001), with a lower
      prevalence of BP target (5.8% [95% confidence interval (CI), 2.9 to 8.6] versus
      21.5% [95% CI, 15.6 to 27.4]; P < 0.0001). The risk for not achieving BP target
      in PC was 2.6 times greater, independently from age, sex, diabetes, and eGFR.
      Fewer antihypertensive drugs were prescribed in PC (1.9 +/- 1.1 versus 2.5 +/-
      1.1; P < 0.0001). In both groups, inhibitors of the renin-angiotensin system were
      the most frequently prescribed drugs (>84%), followed by diuretics (50%).
      However, family physicians almost exclusively prescribed hydrochlorothiazide,
      whereas nephrologists preferentially prescribed furosemide, administered at a
      higher dose than in PC (47 +/- 41 versus 28 +/- 21 mg/d; P = 0.004). CONCLUSION:
      Control of CKD-related hypertension is significantly worse in PC despite a
      greater cardiovascular risk. Barriers to optimal BP control likely are
      represented by a low number of drugs and inadequate diuretic therapy.

PMID- 15983954
TI  - Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind,
      placebo-controlled clinical trial.
AB  - BACKGROUND: Acute tubular necrosis (ATN) occurs commonly in critically ill
      patients and is associated with increased morbidity and mortality. Fenoldopam is
      a dopamine receptor alpha1-specific agonist that increases renal blood flow in
      patients with kidney failure. We hypothesized that administration of low-dose
      fenoldopam during early ATN would decrease the need for dialysis therapy and/or
      incidence of death at 21 days. METHODS: We conducted a prospective, randomized,
      double-blind, placebo-controlled, clinical trial in 155 patients with early ATN.
      Patients were considered eligible for enrollment if serum creatinine level
      increased to 50% greater than admission levels within 24 hours and mean arterial
      pressure was greater than 70 mm Hg. Patients were randomly assigned to the
      administration of placebo or fenoldopam for 72 hours. RESULTS: Overall, 22 of 80
      patients (27.5%) in the fenoldopam group reached the primary end point compared
      with 29 of 75 patients (38.7%) in the placebo group (P = 0.235). This 11%
      absolute reduction in the primary end point was not statistically significant (P
      = 0.23). Similarly, there was no difference in the incidence of dialysis therapy
      between patients randomly assigned to fenoldopam (13 of 80 patients; 16.25%)
      versus the placebo group (19 of 75 patients; 25.3%; P = 0.163). Moreover, there
      was no statistically significant difference in 21-day mortality rates between the
      2 groups (fenoldopam, 13.8% versus placebo, 25.3%; P = 0.068). In secondary
      analyses, fenoldopam tended to reduce the primary end point in patients without
      diabetes and postoperative cardiothoracic surgery patients with early ATN
      (fenoldopam patients without diabetes, 14 of 54 patients [25.9%] versus placebo
      patients without diabetes, 23 of 52 patients [44.2%]; P = 0.048) and
      postoperative cardiothoracic patients (6 of 34 patients [17.6%] versus 14 of 36
      patients [38.8%]; P = 0.049). Conversely, fenoldopam did not improve the primary
      end point in patients with diabetes or those with acute renal failure from other
      causes. A larger multicenter trial using separate randomizations for patients
      with and without diabetes will be needed to determine the efficacy of fenoldopam
      mesylate in specific subpopulations with ATN. CONCLUSION: Fenoldopam does not
      reduce the incidence of death or dialysis therapy in intensive care unit patients
      with early ATN.

PMID- 15983955
TI  - N-terminal pro-B-type natriuretic peptide for predicting coronary disease and
      left ventricular hypertrophy in asymptomatic CKD not requiring dialysis.
AB  - BACKGROUND: N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level predicts
      underlying heart disease in the general population. However, because NT-proBNP
      clearance may depend on renal function, the significance of an elevated level in
      patients with chronic kidney disease (CKD) without cardiac symptoms is uncertain.
      We sought to determine whether there is an association between NT-proBNP level
      and coronary artery disease (CAD) and left ventricular hypertrophy (LVH) in this
      population. METHODS: We enrolled 207 ambulatory patients with CKD not on dialysis
      therapy. Medical records were reviewed for cardiac history and risk factors. NT
      proBNP and troponin T (cTnT) levels were measured. Echocardiograms were analyzed
      from 99 patients. RESULTS: NT-proBNP levels were elevated in 116 patients (56%),
      and 67 patients (33%) had experienced prior CAD events (myocardial infarction or
      revascularization). The prevalence of advanced age, diabetes, prior CAD events,
      myocardial injury (cTnT > 0.03 ng/mL [>0.03 microg/L]), and LVH increased,
      whereas glomerular filtration rate decreased, across quartiles of NT-proBNP
      levels. After adjustment for glomerular filtration rate, cTnT level, age, and
      diabetes, NT-proBNP remained an independent indicator of prior CAD events
      compared with quartile 1 (cTnT range, 4 to 116 pg/mL) for quartile 2 (range, 122
      to 490 pg/mL): odds ratio, 1.6; 95% confidence interval, 0.5 to 5.0; for quartile
      3 (range, 490 to 1,819 pg/mL): odds ratio, 5.3; 95% confidence interval, 1.7 to
      16.2; and for quartile 4 (>1,975 pg/mL): odds ratio, 4.1; 95% confidence
      interval, 1.3 to 13.5. For patients with echocardiograms, NT-proBNP level
      predicted prior CAD events independent of LVH. CONCLUSION: NT-proBNP level
      elevation in asymptomatic patients with CKD reflects underlying ischemic heart
      disease and hypertrophy independent of renal function in a population with
      anticipated high cardiac morbidity.

PMID- 15983956
TI  - Antagonists of aldosterone and proteinuria in patients with CKD: an uncontrolled
      pilot study.
AB  - BACKGROUND: Experimental evidence suggests that aldosterone may contribute to
      progressive kidney disease. Although angiotensin-converting enzyme (ACE)
      inhibitors and angiotensin type 1 receptor antagonists (ARBs) suppress the renin
      angiotensin system, these agents do not adequately control plasma aldosterone
      levels. Hence, administration of aldosterone receptor antagonists may provide
      additional renal benefits to the ACE inhibitors and ARBs. METHODS: In the present
      uncontrolled pilot study, we evaluate the short-term (8 weeks) effects of
      spironolactone on proteinuria in 42 patients with chronic kidney disease (CKD)
      already treated with ACE inhibitors and/or ARBs. RESULTS: Spironolactone (25 mg/d
      for 8 weeks) decreased proteinuria from protein of 2.09 +/- 0.16 to 1.32 +/- 0.08
      g/24 h after 2 weeks and 1.05 +/- 0.08 g/24 h after 8 weeks. Four weeks after
      discontinuation of spironolactone therapy, proteinuria returned to close to
      baseline values. Baseline proteinuria correlated significantly with plasma
      aldosterone level (r = 0.81; P < 0.0001). Moreover, baseline aldosterone level
      correlated significantly with degree of reduction in proteinuria after treatment
      with spironolactone (r = 0.70; P < 0.0001). Spironolactone caused a significant
      increase in serum potassium levels (from 4.4 +/- 0.1 mEq/L [mmol/L] at baseline
      to 4.8 +/- 0.1 mEq/L [mmol/L] after 8 weeks of treatment; P < 0.01). CONCLUSION:
      This study shows that spironolactone may effectively reduce proteinuria in
      patients with CKD. Concerns remain in regard to the risk for hyperkalemia in
      patients with CKD. Prospective randomized trials are necessary to confirm the
      efficacy and safety of antagonists of aldosterone on proteinuria and progression
      of CKD.

PMID- 15983957
TI  - A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary
      cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and
      autosomal dominant glomerulocystic kidney disease.
AB  - BACKGROUND: Autosomal dominant medullary cystic kidney disease type 2 (MCKD2),
      familial juvenile hyperuricemic nephropathy (FJHN), and autosomal dominant
      glomerulocystic kidney disease (GCKD) constitute a hereditary renal disease group
      that may lead to end-stage renal failure caused by mutations of the UMOD gene and
      its product, uromodulin or Tamm-Horsfall protein. Of 34 different UMOD mutations
      described to date, 28 were located in exon 4. Based on such mutation clustering,
      some investigators have proposed that the sequencing of UMOD exon 4 might become
      a preliminary diagnostic test for patients with this phenotype. METHODS: We
      performed linkage analysis and sequencing of the entire codifying region of the
      UMOD gene in 4 Spanish families with MCKD/FJHN/GCKD. RESULTS: All families were
      shown to present mutations in the UMOD gene. In 3 families, the detected
      mutations were located in exon 5. Although 1 novel mutation (Gln316Pro) was
      observed in 2 of these families, a previously reported mutation (Cys300Gly) was
      found in the other kindred. The Cys300Gly mutation was found in the family
      presenting with a GCKD phenotype. CONCLUSION: Our data show a novel mutation
      pattern in UMOD , suggesting that exon 5 mutations can be more frequent in some
      populations. Our results support that every exon of the UMOD gene must be
      included in molecular testing and provide additional evidence for the existence
      of a fourth calcium-binding epidermal growth factor-like domain in the structure
      of Tamm-Horsfall protein. A second family reported to date is described,
      confirming that the GCKD phenotype may be caused by a UMOD mutation.

PMID- 15983959
TI  - Mild hyperphosphatemia and mortality in hemodialysis patients.
AB  - BACKGROUND: Severe hyperphosphatemia (serum phosphate level > 6.5 mg/dL [>2.10
      mmol/L]) has been associated directly with increased overall and cardiovascular
      mortality in hemodialysis (HD) patients. Currently, clinical guidelines recommend
      maintaining phosphate levels within normal range (3.0 to 5.0 mg/dL [0.97 to 1.61
      mmol/L]). However, mild hyperphosphatemia (phosphate, 5.01 to 6.5 mg/dL [1.62 to
      2.10 mmol/L]) is still to be addressed as an independent mortality risk factor in
      HD patients. METHODS: The association between serum phosphate level and survival
      in maintenance HD patients was explored prospectively in 385 incident patients
      from 1990 to 2001. Cox regression was performed using phosphate level as: (1) a
      continuous variable; (2) stratified as low phosphate level (<3 mg/dL [<0.97
      mmol/L]), normal phosphate level (3.0 to 5.0 mg/dL [0.97 to 1.61 mmol/L]), mild
      hyperphosphatemia (phosphate, 5.01 to 6.5 mg/dL [1.62 to 2.10 mmol/L]), or severe
      hyperphosphatemia (phosphate > 6.5 mg/dL [>2.10 mmol/L]); and (3) phosphate level
      greater or less than 5.0 mg/dL (> or <1.61 mmol/L). RESULTS: As a continuous
      variable, relative risk (RR) for mortality for serum phosphate level was 1.26
      (confidence interval [CI], 1.09 to 1.47) after adjusting for age, sex, diabetes,
      Kt/V, albumin level, hemoglobin level, serum calcium level, normalized protein
      catabolic rate, and parathyroid hormone level. Compared with a normal phosphate
      level, mild hyperphosphatemia showed an adjusted mortality RR of 1.94 (CI, 1.17
      to 3.19), and severe hyperphosphatemia, an RR of 2.02 (CI, 1.10 to 3.73).
      Patients with a phosphate level cutoff value greater than 5.0 mg/dL (>1.61
      mmol/L) showed a 2-fold increase in adjusted RR for mortality compared with those
      with a phosphate level of 5.0 mg/dL or less (< or =1.61 mmol/L; RR, 2.11; CI,
      1.44 to 3.08). CONCLUSION: A serum phosphate level greater than 5.0 mg/dL (>1.61
      mmol/L) is independently associated with an increased risk for death in HD
      patients.

PMID- 15983958
TI  - Cinacalcet hydrochloride is an effective treatment for secondary
      hyperparathyroidism in patients with CKD not receiving dialysis.
AB  - BACKGROUND: Secondary hyperparathyroidism develops early in patients with chronic
      kidney disease (CKD). Clinical guidelines from the National Kidney Foundation
      Kidney/Disease Outcomes Quality Initiative emphasize the need to control
      parathyroid hormone (PTH), calcium, and phosphorus levels in patients with CKD
      not receiving dialysis to reduce poor outcomes. This phase 2 study evaluated the
      effects of the oral calcimimetic cinacalcet hydrochloride in patients with CKD
      not on dialysis therapy. METHODS: A randomized, double-blind, placebo-controlled,
      18-week study enrolled adults with an estimated glomerular filtration rate of 15
      to 50 mL/min/1.73 m2 (0.25 to 0.83 mL/s/1.73 m2) and an intact PTH (iPTH) level
      greater than 130 pg/mL (ng/L). Cinacalcet (or placebo) was titrated from 30 to
      180 mg once daily to obtain a 30% or greater reduction in iPTH levels from
      baseline. RESULTS: Baseline mean iPTH levels were 243 pg/mL (ng/L) in the
      cinacalcet group (n = 27) and 236 pg/mL (ng/L) in the control group (n = 27). At
      baseline, 28% of subjects were being administered vitamin D sterols and 43% were
      being administered phosphate binders or calcium supplements. The addition of
      cinacalcet significantly decreased iPTH concentrations compared with controls
      during the efficacy-assessment phase: 56% versus 19% of subjects achieved a 30%
      or greater reduction in iPTH levels (P = 0.006), and mean iPTH levels decreased
      by 32% in the cinacalcet group, but increased by 6% in the control group (P <
      0.001). Mean serum calcium and phosphorus levels remained within normal range
      throughout the study. Cinacalcet generally was well tolerated; the most frequent
      adverse events were gastrointestinal. CONCLUSION: This preliminary study provides
      evidence that cinacalcet is efficacious for the treatment of secondary
      hyperparathyroidism in subjects with CKD not receiving dialysis.

PMID- 15983960
TI  - Beta-fibrinogen haplotypes and the risk for cardiovascular disease in a dialysis
      cohort.
AB  - BACKGROUND: Elevated plasma fibrinogen levels are common in dialysis patients and
      may be related to an elevated risk for cardiovascular disease (CVD). We tested
      the hypothesis that genetic variation in the beta-fibrinogen ( FGB ) gene, shown
      to explain 1% to 5% of fibrinogen level variation in the general population, has
      an important role in elevated fibrinogen levels and excess CVD risk in dialysis
      patients. METHODS: Plasma fibrinogen was measured in 735 dialysis patients a
      median of 3 months from the start of dialysis therapy by using an automated clot
      rate assay. Seven polymorphisms of the FGB gene were determined. Haplotype
      analysis was conducted using the Phase program to estimate haplotypes, with
      stratification for race. CVD events were ascertained from medical records.
      RESULTS: During a median follow-up of 2.1 years, 279 CVD events occurred.
      Genotype frequencies were in Hardy-Weinberg equilibrium. Four common haplotypes
      identified were not associated with fibrinogen levels or CVD risk in the entire
      cohort or after stratification by race. The -455A allele, known to increase gene
      expression in vitro, was marginally associated with fibrinogen levels only in
      patients without diabetes (regression coefficient [beta], 20 mg/dL [for +1 copy
      of the A allele; P = 0.06]), adjusted for age, sex, race, smoking, baseline
      dialysis modality, comorbidity, and history of diabetes and CVD. Post hoc
      analysis showed that -249C-->T (defining haplotype 3) was associated with greater
      fibrinogen levels and CVD risk among patients without diabetes and current
      smokers. CONCLUSION: The FGB gene likely does not have an important role in
      determining the variation in elevated plasma fibrinogen levels or excess CVD risk
      in dialysis patients.

PMID- 15983961
TI  - Comparison of surgically removed cardiac valves of patients with ESRD with those
      of the general population.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) have increased vascular
      and valvular calcification compared with the general population. Recently, 44% of
      renal transplant recipients were found to have vascular calcification of the
      medial layer of the inferior epigastric artery that was associated with
      deposition of bone matrix proteins. Similar findings have been reported for
      native and bioprosthetic cardiac valves surgically removed from patients without
      ESRD. METHODS: To determine whether valvular calcification in patients with ESRD
      is similar to that in patients without ESRD, we retrospectively examined
      surgically excised native cardiac valves of all hemodialysis patients and
      compared them pathologically with those of matched controls without renal
      failure. Valves were examined by using routine stains and immunohistochemistry
      for markers to endothelial cells, macrophages, B and T lymphocytes, alkaline
      phosphatase, osteopontin, and bone morphogenic protein 4. RESULTS:
      Histologically, 7 of 10 valves from patients with ESRD had moderate to severe
      inflammation compared with 1 of 10 valves from control patients. Patients with
      ESRD had more endothelial cells/vascularity (P = 0.002) and macrophages (P =
      0.069). There was no difference between the 2 groups with respect to B and T
      lymphocytes, alkaline phosphatase, osteopontin, or bone morphogenic protein 4.
      CONCLUSION: The noncollagenous proteins bone morphogenic protein and osteopontin
      have been shown in surgically removed cardiac valves of patients with ESRD and
      the general population. However, valvular calcification in patients with ESRD is
      associated with enhanced inflammation, consistent with the previously reported
      greater C-reactive protein levels in this patient population and their increased
      risk for death.

PMID- 15983962
TI  - Effect of spironolactone on blood pressure and the renin-angiotensin-aldosterone
      system in oligo-anuric hemodialysis patients.
AB  - BACKGROUND: Through its actions on nonepithelial tissues, including brain, blood
      vessels, and heart, aldosterone may mediate hypertension, cardiac hypertrophy,
      and fibrosis. Whether aldosterone has a direct pathogenic role in the development
      of cardiovascular complications in patients with end-stage renal disease is
      unknown. Oligo-anuric dialysis patients provide a clinical setting to study the
      effects of the mineralocorticoid receptor blocker spironolactone that are
      independent of the diuretic properties of the drug. We performed a randomized,
      double-blinded, placebo-controlled, crossover study to assess the effect of
      spironolactone on blood pressure and the renin-angiotensin-aldosterone system in
      oligo-anuric hemodialysis patients. METHODS: Eight hemodialysis patients were
      administered either spironolactone, 50 mg, or placebo orally twice daily for 2
      weeks, followed by a 3-week washout period, after which patients crossed over in
      their treatment arms for 2 more weeks. RESULTS: Administration of spironolactone
      for 2 weeks decreased predialysis systolic blood pressure from 142.0 +/- 19.6 to
      131.4 +/- 18.2 mm Hg (P < 0.05). Compared with placebo, a 2-week course of
      spironolactone had no effect on predialysis and postdialysis plasma potassium or
      aldosterone concentrations or renin activity. CONCLUSION: When administered for 2
      weeks, spironolactone, 50 mg twice daily, reduced predialysis systolic blood
      pressure, but did not produce hyperkalemia in oligo-anuric hemodialysis patients.

PMID- 15983963
TI  - Oxidative metabolism appears to be reduced in long-term hemodialysis patients.
AB  - BACKGROUND: As part of a study of whole-body protein metabolism in hemodialysis
      (HD) patients, we obtained values for whole-body bicarbonate production in
      control subjects and HD patients before and during dialysis by using stable
      isotopically labeled bicarbonate. Indirect calorimetry measurements have shown
      normal or increased energy expenditure in HD patients, which has been used to
      explain the malnutrition in many of these patients. However, this method becomes
      inaccurate when the dynamics of whole-body bicarbonate production change during
      measurement, as is the case with HD patients during dialysis. METHODS: Whole-body
      bicarbonate production was measured in 6 control subjects, 9 patients on a
      nondialysis day (HD-), and 8 patients during an HD session (HD+) by means of a
      primed constant infusion of carbon 13 (13C)-labeled sodium carbonate (NaH13CO3).
      13C-abundance of expired carbon dioxide was measured by means of isotope ratio
      mass spectrometry. RESULTS: Carbon dioxide production was 141 +/- 12, 123 +/-
      11*, and 148 +/- 19 micromol/kg/min for the control, HD-, and HD+ groups,
      respectively (*P < 0.05 compared with the control and HD+ groups). Values for
      energy expenditure were derived and were 29.1 +/- 2.4, 24.9 +/- 2.1*, and 32.6 +/
      2.0 kcal/kg/day, respectively (*P < 0.05 compared with the control and HD+
      groups). CONCLUSION: Whole-body oxidation in HD patients is reduced compared with
      control subjects. During dialysis, bicarbonate turnover, as well as carbon
      dioxide expiration, increases because of the influx of bicarbonate from the
      dialyzer.

PMID- 15983964
TI  - Peer mentoring: a culturally sensitive approach to end-of-life planning for long
      term dialysis patients.
AB  - BACKGROUND: This study is designed to explore the impact of peer mentoring on end
      of-life decision making. METHODS: A controlled randomized intervention study with
      203 patients from 21 dialysis centers across Michigan explored the impact of peer
      mentors, dialysis patients trained to help other patients, on end-of-life
      planning. RESULTS: Communicating information on advance directives (ADs) through
      peer mentoring significantly influenced the completion of ADs overall compared
      with distributing standard printed material or no specific designed intervention.
      However, the influence was most prominent among African Americans, not only
      increasing actual completion of ADs (P < 0.001) and comfort discussing ADs (P <
      0.01), but also improving subjective well-being (P < 0.05) and anxiety (P < 0.05)
      during the study period. These effects of peer mentoring did not appear among
      white patients, although printed material on ADs decreased reported suicidal
      ideation (P < 0.05). CONCLUSION: These results suggest the importance of
      addressing specific cultural factors in the process of AD education. Common
      practice assumes that printed materials are effective in educating patients about
      health care and decision making. However, peer mentoring, a relationship-centered
      person-to-person approach, may be more effective in some cultural groups because
      it partakes of oral, rather than written, traditions. Acknowledging cultural
      differences and tailoring our approach could be powerful in enhancing trust and
      participation and decreasing potential disparities in health care outcomes.

PMID- 15983965
TI  - Enzyme replacement therapy in Fabry disease patients undergoing dialysis: effects
      on quality of life and organ involvement.
AB  - BACKGROUND: Fabry disease is a lysosomal storage disease resulting from deficient
      alpha-galactosidase A (alpha-Gal A) activity. End-stage renal disease generally
      occurs around the fourth decade of age, and dialysis therapy is a life-saving
      procedure. For patients with Fabry disease undergoing dialysis, death usually
      occurs from cardiac or cerebrovascular complications. Recently, enzyme
      replacement therapy was introduced for treatment of the disease. METHODS: We
      report results of several clinical outcomes after 2 years of treatment with alpha
      Gal A in patients with Fabry disease undergoing dialysis. Nine dialysis patients
      underwent a complete clinical, cardiac, and cerebrovascular evaluation at
      baseline and after 24 months of treatment. Two patients reported a recurrent pain
      crisis, and 6 patients reported gastrointestinal symptoms. In all patients,
      enzyme replacement therapy was undertaken because of the presence of Fabry
      cardiomyopathy. A complete echocardiographic study was performed in 6 patients 12
      and 24 months before and 12 and 24 months during enzyme replacement therapy.
      RESULTS: Enzyme replacement therapy was well tolerated. Pain crises disappeared
      completely after approximately 6 months of treatment, and patients with
      gastrointestinal involvement reported improvement in symptoms after 6 to 8
      months. At baseline, all patients had left ventricular concentric hypertrophy.
      Enzyme replacement therapy did not affect heart rate or mean arterial pressure.
      The mean slope of left ventricular mass index progression decreased from 0.98 +/-
      0.01 in the pretreatment period (24 months) to 0.46 +/- 0.960 in the enzyme
      replacement-therapy period (P = 0.06). CONCLUSION: Our observation indicates that
      in dialysis patients, enzyme replacement therapy is safe and effective, improving
      global quality of life and possibly ameliorating the progression of typical Fabry
      cardiomyopathy.

PMID- 15983967
TI  - Baseline comorbidity in kidney transplant recipients: a comparison of comorbidity
      indices.
AB  - BACKGROUND: An increasing number of patients starting renal replacement therapy
      are older and have complex comorbidity. In keeping with these demographics, an
      increased number of older patients undergo transplantation each year. To date, no
      study has reported baseline comorbidity characteristics of those who underwent
      transplantation, validated the use of comorbidity indices, or asked whether
      comorbidity predicts patient outcome after kidney transplantation. Our objective
      is to report baseline comorbidity and compare the use of different indices for
      recipients of kidneys from both deceased and living donors. METHODS: Using data
      from the Canadian Organ Replacement Registry, we tested the ability of 4
      comorbidity indices to predict patient survival by using a Cox regression model.
      Model covariates included donor source, age, race, sex, treatment period, primary
      renal disease cause, months on dialysis therapy, and comorbidities. RESULTS: A
      total of 6,324 patients were included; 22% had > or =1 comorbid condition at
      baseline. After adjustment for age, sex, and cause of renal disease, increased
      comorbidity was associated strongly with reduced patient survival. Of all
      comorbidity indices examined, the model containing the Charlson Comorbidity Index
      (CCI) offered the best fit. The model containing log--CCI had an index of
      concordance of 74%. CONCLUSION: The CCI is a suitable tool for the measurement of
      comorbidity in renal transplant recipients.

PMID- 15983966
TI  - Hypokalemia in Chinese peritoneal dialysis patients: prevalence and prognostic
      implication.
AB  - BACKGROUND: Abnormal potassium metabolism may contribute to the increased cardiac
      morbidity and mortality seen in dialysis patients. We studied the pattern of
      serum potassium levels in a cohort of Chinese peritoneal dialysis (PD) patients.
      METHODS: We studied serum potassium levels of 266 PD patients during 3
      consecutive clinic visits. Dialysis adequacy, residual renal function, and
      nutritional status also were assessed. Patients were followed up for 33.7 +/-
      20.7 months. RESULTS: Mean serum potassium level was 3.9 +/- 0.5 mEq/L (mmol/L).
      Five patients (1.9%) had an average serum potassium level less than 3 mEq/L
      (mmol/L), whereas 54 patients (20.3%) had a serum potassium level less than 3.5
      mEq/L (mmol/L). Serum potassium levels correlated with overall Subjective Global
      Assessment score (r = 0.276; P < 0.001) and serum albumin level (r = 0.173; P =
      0.005) and inversely with Charlson comorbidity score (r = -0.155; P = 0.011).
      There was no correlation between serum potassium level and daily PD exchange
      volume, total Kt/V, urine volume, or residual glomerular filtration rate. By
      means of multivariate analysis with Cox proportional hazard model to adjust for
      confounders, serum potassium level was an independent predictor of actuarial
      patient survival. PD patients with hypokalemia (serum potassium < 3.5 mEq/L
      [mmol/L]) had significantly worse actuarial survival (hazard ratio, 1.79; 95%
      confidence interval, 1.12 to 2.85; P = 0.015) than those without hypokalemia
      after adjusting for confounding factors. CONCLUSION: Hypokalemia is common in
      Chinese PD patients. Serum potassium level was associated with nutritional status
      and severity of coexisting comorbid condition. Furthermore, hypokalemia was an
      independent predictor of survival in PD patients. Additional studies may be
      needed to investigate the benefit of potassium supplementation for PD patients
      with hypokalemia.

PMID- 15983968
TI  - Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria
      (pyroglutamic aciduria) acquired in hospital.
AB  - A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an
      organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several
      other drugs have been implicated in the development of transient 5-oxoprolinemia
      in adults. We report the case of a patient with lymphoma who was admitted for
      salvage chemotherapy. The patient subsequently developed fever and neutropenia
      and was administered 20.8 g of acetaminophen during 10 days. During this time,
      anion gap increased from 14 to 30 mEq/L (14 to 30 mmol/L) and altered mental
      status developed. After usual causes of high anion gap acidosis were ruled out, a
      screen for urine organic acids showed 5-oxoproline levels elevated at 58-fold
      greater than normal values. Predisposing factors in this case included renal
      dysfunction and sepsis. Clinicians need to be aware of this unusual cause of
      anion gap acidosis because it may be more common than expected, early
      discontinuation of the offending agent is therapeutic, and administration of N 
      acetylcysteine could be beneficial.

PMID- 15983969
TI  - Geriatrics.

PMID- 15983970
TI  - Acute renal failure in a renal allograft: an unusual infectious cause of
      thrombotic microangiopathy.

PMID- 15983973
TI  - Hemodiafiltration does not increase the risk for mortality in ESRD.

PMID- 15983975
TI  - Shorter unassisted patency of vascular access after angioplasty in women.

PMID- 15983979
TI  - Presence and maturity of dendritic cells in melanoma lymph node metastases.
AB  - Immune avoidance mechanisms play a key role in the successful dissemination of
      melanoma. One mechanism whereby this could be achieved is by interfering with
      dendritic cell (DC) presentation of tumour-associated antigens to naive T cells.
      In particular, immature DCs characterized by the absence of accessory molecules
      are known to be immunosuppressive and to be involved in the induction of
      tolerance. The present study has investigated the presence and activation status
      of DCs within melanoma metastases in the regional lymph nodes. Using image
      analysis techniques, the expression of Factor XIIIa (FXIIIa), CD40, CD83 and HLA
      DR and the morphological features of DCs were examined in paraffin sections from
      26 lymph nodes containing melanoma metastases. DCs expressing FXIIIa were found
      in 70% of the lymph nodes. The number of DCs identified was generally small but
      there were more concentrated areas of DCs designated as hotspots. In these areas
      of high FXIIIa staining, the percentage area occupied by DCs varied between 0.1%
      and 10%. The majority of FXIIIa-positive cells did not express the DC maturation
      markers CD83 or CD40 and morphologically were rounded with few dendrites,
      indicating that they were immature. The cells did, however, express high levels
      of HLA-DR, suggesting that they have the ability to present antigen but lack the
      accessory molecules required to initiate an immune response. Immature DCs,
      characterized by phenotypic and morphological features, are therefore present
      within the tumour deposits in lymph nodes infiltrated by melanoma and may
      specifically modulate the anti-melanoma immune response.

PMID- 15983980
TI  - Factors affecting the efficacy of non-fumigant nematicides for controlling root
      knot nematodes.
AB  - Second-stage juveniles (J2) and egg masses of root-knot nematodes as well as root
      debris heavily infected by the latter were exposed for different periods of time
      to six different doses of the nematicides cadusafos and fenamiphos. The efficacy
      of the nematicides increased significantly with increasing exposure time. Both
      nematicides were more effective against J2, although they could not provide
      acceptable control of J2 inside egg masses or heavily galled root debris. The
      effect of different application strategies on the efficacy and persistence of
      certain nematicides was also assessed in a field study. Cadusafos, fenamiphos,
      fosthiazate and oxamyl were applied in field micro-plots either as a single full
      dose at the time of crop establishment or as multiple reduced-rate applications
      at 14-day intervals throughout the cropping period, and their efficacy and
      persistence were determined using bioassays and analytical studies. Fosthiazate
      was the most efficient nematicide studied, and this was mainly attributed to its
      long soil persistence. Oxamyl also provided adequate nematode control for the
      first 48-56 days after its application, regardless of the application method used
      and its relatively rapid field dissipation. Fenamiphos and cadusafos failed to
      provide adequate nematode control, although cadusafos was the most persistent of
      the nematicides tested. The failure of fenamiphos to provide adequate nematode
      control was mainly attributed to its rapid degradation by soil micro-organisms,
      which were stimulated after its repeated low-rate application at 14-day
      intervals. In contrast cadusafos failure was attributed to the inability of the
      nematicide to reduce nematode populations even at relatively high concentrations
      in soil.

PMID- 15983981
TI  - COG4849 is a novel family of nucleotidyltransferases.
AB  - Only a minority of currently known protein families is characterized
      structurally. This makes homology-based structure modeling an essential
      instrument that can be viewed as the first approximation to experimental
      determination of protein structure. Using sequence similarity searches, we
      detected a distant similarity between a family of uncharacterized hypothetical
      proteins, COG4849, and the family of tRNA nucleotidyltransferases. The suggested
      remote homology between the N-terminal domain of COG4849 and the catalytic domain
      of tRNA nucleotidyltransferase was further supported by comparison of sequence
      profiles, methods for fold recognition and structure modeling. The combined
      multiple alignment of the two families reveals shared conservation of
      functionally important motifs and suggests the similarity in catalytic mechanisms
      of the performed reactions. Our results suggest that (i) the N-terminal domain of
      proteins from COG4849 shares structural similarity with the catalytic domain of
      tRNA nucleotidyltransferase, and (ii) this domain catalyzes the nucleotidyl
      transfer reaction involving two metal ions.

PMID- 15983982
TI  - Reciprocal changes in trefoil 1 and 2 expression in stomachs of mice with gastric
      unit hypertrophy and inflammation.
AB  - H+/K+-ATPase beta-subunit-deficient mice (129/Sv background) display numerous
      pathologies in the stomach. Expression of the mutation in BALB/cCrSlc mice
      results in the development of an aberrant 'mucus-rich' cell population. 'Mucus
      rich' cells have been described in stomachs of mice with autoimmune gastritis, a
      disease mediated by CD4+ T cells. Other pathological features of autoimmune
      gastritis are similar to those in H+/K+ beta-deficient mice and include a
      mononuclear cell infiltrate in the gastric mucosa, non-functional or absent
      parietal cells, depletion of zymogenic cells, hypergastrinaemia, and gastric unit
      hypertrophy caused by immature cell hyperplasia. The present study investigates
      further the aberrant gastric 'mucus-rich' cell lineage and analyses the mRNA
      expression of mucus cell products TFF1 and TFF2. 'Mucus-rich' cells stained for
      both acidic and neutral mucins, and with a TFF2-specific antibody. Stomachs from
      both models expressed decreased TFF1 mRNA and reciprocally increased TFF2 mRNA.
      The involvement of gastrin in regulating trefoil mRNA expression was also
      investigated using gastrin-deficient mice. In contrast to previous findings,
      gastrin did not positively regulate TFF1 mRNA expression, but there was possible
      augmentation of TFF2. Additionally, a clear role for inflammation was established
      involving both polymorphonuclear and mononuclear cells in these models, and a
      link was found between mucosal hypertrophy and increased interleukin-11 (IL-11)
      expression.

PMID- 15983983
TI  - Use of myeloid growth factors for patients with febrile neutropenia: plus ca
      change, plus c'est la meme chose.

PMID- 15983984
TI  - Varying Ti-6Al-4V surface roughness induces different early morphologic and
      molecular responses in MG63 osteoblast-like cells.
AB  - Osteoblast response to Ti implants depends not only on the chemistry of the
      implant but also on the physical properties of the implant surface, such as
      microtopography and roughness. This study was undertaken to examine early changes
      in cell morphology and gene expression during the early phase of osteoblast
      interaction with titanium alloy (Ti-6Al-4V) surfaces of two different
      roughnesses. MG63 osteoblast-like cells were cultured for 2, 6, 24, and 72 h on
      smooth (Ra=0.18+/-0.03 microm) and rough (Ra=2.95+/-0.23 microm) Ti-6Al-4V
      surfaces. Changes in cell proliferation were assessed by measuring cell number
      after 72 h in culture. Morphological characteristics were observed by scanning
      electron microscopy after 2, 6, and 24 h of culture. Changes in gene expression
      for extracellular signal-regulated kinase 2 (Erk2), type I collagen (alpha2[I]
      collagen), phospholipase C-gamma2 (Plc-gamma2), and beta-actin were measured by
      RT-PCR after 6 and 24 h in culture. Cell number was significantly higher on the
      smooth surface. In scanning electron micrographs, cells on smooth Ti-6Al-4V were
      spherical and raised up from the surface after 2 h in culture. In contrast, cells
      on the rough surface adopted an irregular, elongated shape that spanned across
      pits in the surface. At 24 h, cells on the smooth surface had flattened, become
      elongate, and covered the surface. In contrast, cells on the rough surface
      appeared more differentiated in shape and the margins of the cells were
      irregular, with many processes extending out, following the contour of the
      surface. Of the genes examined, only Erk2 and beta-actin showed a change in
      expression with surface roughness. Both genes were upregulated (p<0.05) on the
      rough surface at 6 h. These results indicate that Ti-6Al-4V surface roughness
      affects osteoblast proliferation, morphology, and gene expression, and that these
      effects can be measured after periods as short as 2-6 h.

PMID- 15983985
TI  - Differences in colorectal carcinoma stage and survival by race and ethnicity.
AB  - BACKGROUND: In the United States, blacks with colorectal carcinoma (CRC)
      presented with more advanced-stage disease and had higher mortality rates
      compared with non-Hispanic whites. Data regarding other races/ethnicities were
      limited, especially for Asian/Pacific Islander and Hispanic white subgroups.
      METHODS: Using data from 11 population-based cancer registries that participate
      in the Surveillance, Epidemiology and End Results program, the authors evaluated
      the relation among 18 different races/ethnicities and disease stage and mortality
      rates among 154,103 subjects diagnosed with CRC from 1988 to 2000. RESULTS:
      Compared with non-Hispanic whites, blacks, American Indians, Chinese, Filipinos,
      Koreans, Hawaiians, Mexicans, South/Central Americans, and Puerto Ricans were 10
      60% more likely to be diagnosed with Stage III or IV CRC. Alternatively, Japanese
      had a 20% lower risk of advanced-stage CRC. With respect to mortality rates,
      blacks, American Indians, Hawaiians, and Mexicans had a 20-30% greater risk of
      mortality, whereas Chinese, Japanese, and Indians/Pakistanis had a 10-40 % lower
      risk. CONCLUSIONS: The authors observed numerous racial/ethnic disparities in the
      risks of advanced-stage cancer and mortality among patients with CRC, and there
      was considerable variation in these risks across Asian/Pacific Islander and
      Hispanic white subgroups. Although the etiology of these disparities was
      multifactorial, developing screening and treatment programs that target
      racial/ethnic populations with elevated risks of poor CRC outcomes may be an
      important means of reducing these disparities.

PMID- 15983986
TI  - Sociodemographic determinants of cancer treatment health literacy.
AB  - BACKGROUND: Ethnic and racial disparities in cancer outcomes are often attributed
      to sociodemographic factors, including income, education, insurance status, and
      access to quality cancer care. Less attention has been directed toward other
      possible contributors, such as misconceptions about cancer and its treatment.
      METHODS: Nine hundred fifty-seven U.S. adults who reported that they had never
      been diagnosed with cancer were identified and surveyed using a random digit
      dialing telephone survey. Sociodemographic associations with endorsement of five
      misconceptions about cancer treatment were evaluated by weighted logistic
      regression. RESULTS: The most prevalent misconception, "Treating cancer with
      surgery can cause it to spread throughout the body," was endorsed as true by 41%
      of the respondents. The second most prevalent misconception, "The medical
      industry is withholding a cure for cancer from the public in order to increase
      profits, " was identified as true by 27%. The statement, "Pain medications are
      ineffective against cancer pain, " was accurately rejected by 68% of the
      respondents, and 89% of the respondents correctly disagreed with the statement,
      "All you need to beat cancer is a positive attitude, not treatment. " Eighty
      seven percent of the respondents were able to identify the statement, "Cancer is
      something that cannot be effectively treated," as false. Respondents who were
      older, nonwhite, Southern, or indicated being less informed about cancer endorsed
      the most misconceptions. CONCLUSIONS: The prevalence of at least three of the
      five cancer misconceptions was unacceptably high, and varied by several
      sociodemographic factors. These beliefs may increase the risk for cancer
      morbidity and mortality because of poor adherence to treatment regimens.

PMID- 15983988
TI  - Effect of microtextured surfaces on the performance of percutaneous devices.
AB  - Along the percutaneous part of implantable devices, like (semi-)permanent
      catheters, epithelial downgrowth can occur. This process can eventually lead to
      implant loss. Various treatments for the catheter surface have been proposed, to
      improve their performance. The purpose of the current study was to investigate
      the effect of a microgroove pattern on the tube surface, on epithelial
      downgrowth. Catheterlike implants were made of silicone tubes, with anchoring
      cuffs made of titanium-fiber mesh. A thin sheet of silicone with microgrooves was
      applied on the tubes. Two types of texturing were used, a square groove of 10
      microm wide and 1 microm deep; or a V-shaped groove of 40 microm wide. The
      grooves were directed either along the long axis of the catheter tube (grooves
      perpendicular to the skin surface) or circling around the catheter (grooves
      directed parallel to the skin surface). As controls, catheters with a smooth
      outer surface were used. Implants were placed in 30 rats, with a follow-up period
      of 9 weeks. During this time, animals were inspected biweekly, and catheter exit
      sites were evaluated using a scoring system. At the end of the 9-week period the
      implants and surrounding tissues were processed for histological evaluation. For
      the clinical evaluation of the exit sites, no statistical differences were found
      between the study groups. Histologically, epithelial downgrowth was observed for
      all samples. The histomorphometrical measurements showed that there were no
      differences in downgrowth between the smooth and parallel-grooved catheters.
      However, there was increased epithelial downgrowth along the catheters with
      grooves perpendicular to the skin. In conclusion, a grooved microtexture can
      direct epithelial tissue ingrowth, but this study found no beneficial effects of
      the guidance phenomenon.

PMID- 15983987
TI  - Secondary pneumatization of the maxillary sinus in callitrichid primates:
      insights from immunohistochemistry and bone cell distribution.
AB  - The paranasal sinuses remain elusive both in terms of function and in the
      proximate mechanism of their development. The present study sought to describe
      the maxillary sinuses (MSs) in three species of callitrichid primates at birth, a
      time when secondary pneumatization occurs rapidly in humans. The MSs were
      examined in serially sectioned and stained slides from the heads of two
      Callithrix jacchus, one Leontopithecus rosalia, and two Saguinus geoffroyi.
      Specimens were examined microscopically regarding the distribution of osteoclasts
      and osteoblasts along the osseous boundaries of the MS and other parts of the
      maxillary bone. Selected sections were immunohistochemically evaluated for the
      distribution of osteopontin (OPN), which facilitates osteoclast binding. Taken
      together, OPN immunoreactivity and bone cell distribution suggested trends of
      bone resorption/deposition that were consistent among species for the superior
      (roof) and inferior (floor) boundaries of the MS. Expansion at the roof and floor
      of the MS appeared to correspond to overall vertical midfacial growth in
      callitrichids. Much more variability was noted for the lateral (alveolar) and
      medial (nasal walls) of the MS. Unlike the other species, the nasal wall of
      Saguinus was static and mostly composed of inferior portions of the nasal capsule
      that were undergoing endochondral ossification. The variation seen in the
      alveolar walls may relate to the presence or absence of adjacent structures,
      although it was noted that adjacency of deciduous molars influenced medial drift
      of the alveolar wall in Saguinus but not Leontopithecus. The results of this
      study are largely consistent with the "structural" or "architectural" hypothesis
      of sinus formation with respect to vertical MS enlargement, and the variable
      cellular/OPN distribution found along the nasal and alveolar walls was evocative
      of Witmer's (J Vert Paleontol 1997;17:1-73) epithelial hypothesis in revealing
      that most expansion occurred in regions unopposed by adjacent structures.

PMID- 15983989
TI  - Electrochemical studies on zirconium and its biocompatible alloys Ti-50Zr at.%
      and Zr-2.5Nb wt.% in simulated physiologic media.
AB  - Different electrochemical studies were carried out for Zr and its biocompatible
      alloys Ti-50Zr at.% and Zr-2.5Nb wt.% in solutions simulating physiologic media,
      Ringer and PBS (phosphate buffered saline) solutions. The results from rest
      potential measurements showed that the three materials are spontaneously
      passivated in both solutions and that the Ti-50Zr alloy has the greatest tendency
      for spontaneous oxide formation. Some corrosion parameters (such as the pitting
      and repassivation potentials) were obtained via cyclic voltammetry in both
      solutions, revealing that the Ti-50Zr has the best corrosion protection while Zr
      has the worst. On the other hand, the pre-anodization (up to 8 V vs. SCE) of the
      alloys in a 0.15 mol/L Na2SO4 solution led to a significant improvement in their
      protection against pitting corrosion when exposed to the Ringer solution.
      Elemental analyses by EDX showed that during pitting corrosion, there is no
      preferential corrosion of any of the alloying elements (Zr, Ti, Nb).

PMID- 15983990
TI  - Composition-controlled nanocomposites of apatite and collagen incorporating
      silicon as an osseopromotive agent.
AB  - The development of a novel biocomposite of apatite (Ap) and collagen
      incorporating low-level additions of silicon (Si) as an osseopromotive agent is
      detailed. Designed to mimic the structural and compositional characteristics of
      developing bone, this composite is produced via a coprecipitation method, through
      which the weight percentage of Ap (i.e., the Ap/collagen ratio) can be varied.
      Coprecipitates produced at Ap contents of 80 wt % (Ap/collagen=4:1), 60 wt %
      (Ap/collagen=3:2), and 40 wt % (Ap/collagen=2:3) Ap showed markedly different
      morphologies, ranging from ceramic-like particulates to rope-like macro-fibrils;
      at all three Ap contents, however, the nanostructural features of the composites
      remained qualitatively indistinguishable, with equiaxed Ap nanocrystals
      distributed randomly throughout a matrix of amorphous collagen. Si incorporation
      was observed to occur preferentially in the collagenous phase-a result with
      potential impact on local controlled release of Si.

PMID- 15983991
TI  - Improving delivery of hydrophobic drugs from hydrogels through cyclodextrins.
AB  - A simple and effective technique of improving delivery of hydrophobic drugs from
      swellable systems is presented. Conventional methods of drug loading in hydrogel
      systems are limited by the characteristics of the pharmacological agent. The
      approach we present uses complexants to modulate drug release. Crosslinked
      poly(ethylene glycol) (PEG) hydrogels were synthesized, characterized, and used
      for vascular applications. The release of cyclosporine (CyA) from PEG hydrogels
      is significantly altered by the sterilization techniques. It was hypothesized
      that the release of CyA from PEG hydrogels can be modulated by using complexants.
      A cyclodextrin-CyA complex solution was prepared and used for drug loading. The
      sterilized PEG hydrogels that were loaded using the cyclodextrin-CyA complex
      solution had favorable release characteristics compared with the release from PEG
      hydrogels that were loaded using the conventional technique. Hence, drug release
      from swellable systems can be tailored by the application of this strategy.

PMID- 15983992
TI  - Structural and mechanical characteristics of silk fibroin and chitosan blend
      scaffolds for tissue regeneration.
AB  - The expanding field of tissue engineering has required the necessity of
      developing biomaterials that are tissue compatible, biodegradable, and comparable
      in mechanical properties to that of native tissue. We propose that the blending
      of two natural polymers, silk fibroin (SF) and chitosan (CS), into a 3D scaffold
      will provide unique chemical, structural, and mechanical properties that can be
      utilized for in vivo tissue regeneration. SF is an attractive material for
      biomedical applications because it is a fibrous protein that has high
      permeability to oxygen and water, relatively low thrombogenicity, low
      inflammatory response, protease susceptibility, supports cell adhesion and
      growth, and, foremost, high tensile strength with flexibility. CS is a
      crystalline polysaccharide, with structure similar to glycosaminoglycans, that
      has good wound healing properties, is nontoxic, and has minimal foreign body
      reactions. We hypothesized that increasing the SF-to-CS ratio would increase the
      ultimate tensile strength and elastic modulus and decrease the water capacity of
      the SFCS scaffolds. With increasing content of silk fibroin, it is observed that
      the ultimate tensile strength and elastic modulus increase significantly. The
      ultimate tensile strength and the elastic modulus were significantly higher in
      the short axis direction for 25:75 and 50:50 SFCS blends as compared to the long
      axis (p<0.05), while they were similar for the 75:25 SFCS blend. However, no
      differences were observed in the strain at failure among blends or due to
      directionality of applied strain. Increasing the chitosan content resulted in an
      increased water capacity of SFCS blends.

PMID- 15983993
TI  - Au(III), Pd(II), Ni(II), and Hg(II) alter NF kappa B signaling in THP1 monocytic
      cells.
AB  - The transcription factor NFkappaB plays a key role in the tissue inflammatory
      response. Metal ions released into tissues from biomaterials (e.g., Au, Pd, Ni,
      Hg) are known to alter the binding of NFkappaB proteins to DNA, thereby
      modulating the effect of NFkappaB on gene activation and, ultimately, the tissue
      response to biomaterials. Little is known about the effect of these metals on key
      signaling steps prior to NFkappaB-DNA binding such as transcription factor
      activation or nuclear translocation, yet these steps are equally important to
      modulation of the pathway. Oxidative stress is known to alter NFkappaB proteins
      and is suspected to play a role in metal-induced NFkappaB signaling modulation.
      Our aim in the current study was to assess the effects of sublethal levels of Ni,
      Hg, Pd, and Au ions on NFkappaB activation and nuclear translocation in the
      monocyte, which is acknowledged as an important orchestrator of the biological
      response to materials and the pathogenesis of chronic disease. Sublethal
      concentrations of Au(III), Ni(II), Hg(II), and Pd(II) were added to cultures of
      human THP1 monocytic cells for 72 h. In parallel cultures, lipopolysaccharide
      (LPS) was added for the last 30 min to activate the monocytic cells. Then
      cellular cytoplasmic and nuclear proteins were isolated, separated by
      electrophoresis, and probed for IkappaBalpha degradation (activation) and
      NFkappaB p65 translocation. Protein levels were digitally quantified and
      statistically compared. The levels of reactive oxygen species (ROS) in the
      monocytic cells were measured as a possible mechanism of metal-induced NFkappaB
      modulation. Only Au(III) activated IkappaBalpha degradation by itself. Au(III)
      and Pd(II) enhanced LPS-induced IkappaBalpha degradation, but Hg(II) and Ni(II)
      suppressed it. Au(III), Ni(II), and Pd(II) activated p65 nuclear translocation
      without LPS, and all but Ni(II) enhanced LPS-induced translocation. Collectively,
      the results suggest that these metal ions alter activation and translocation of
      NFkappaB, each in a unique way at unique concentrations. Furthermore, even when
      these metals had no overt effects on signaling by themselves, all altered
      activation of signaling by LPS, suggesting that the biological effects of these
      metals on monocytic function may only be manifest upon activation. None of the
      metal ions elevated levels of ROS at 72 h, indicating that ROS were probably not
      direct modulators of the NFkappaB activation or translocation at this late time
      point.

PMID- 15983994
TI  - A model for studying epithelial attachment and morphology at the interface
      between skin and percutaneous devices.
AB  - Percutaneous devices are indispensable in modern medicine, yet complications from
      their use result in significant morbidity, mortality, and cost. Bacterial biofilm
      at the device exit site accounts for most infections in short-term devices. We
      hypothesize that advanced biomaterials can be developed that facilitate
      attachment of skin cells to percutaneous devices, forming a seal to preclude
      bacterial invasion. To study the skin/biomaterial interface systematically, we
      first identified biomaterials with physical properties compatible with
      histological processing of skin. Second, we developed an organ culture system to
      study skin response to implants. Organ cultures implanted with porous poly(2
      hydroxyethyl methacrylate) [poly(HEMA)] or polytetrafluoroethylene (PTFE) could
      easily be evaluated histologically with preservation of the skin/biomaterial
      interface. Epithelial cells migrated down the cut edges of the biomaterial in a
      pattern seen in marsupialization of percutaneous devices in vivo. This in vitro
      model maintains skin viability and allows histologic evaluation of the
      skin/biomaterial interface, making this a useful, inexpensive test-bed for
      studies of epidermal attachment to modified biomaterials.

PMID- 15983995
TI  - Bone formation in calvarial defects of Sprague-Dawley rats by transplantation of
      calcium phosphate glass.
AB  - The purpose of this study was to investigate the bone-regenerative effect of
      calcium phosphate glass in vivo. We prepared amorphous calcium phosphate glass
      powder having a mean particle size of 400 microm in the system CaO-CaF2-P2O5-MgO
      ZnO. Calvarial critical-sized defects (8 mm) were created in 60 male Sprague
      Dawley rats. The animals were divided into an experimental group and control
      group of 30 animals each. Each defect was filled with a constant weight of 0.5 g
      calcium phosphate glass powder mixed with saline. As a control, the defect was
      left empty. The rats were sacrificed 2, 4, or 8 weeks postsurgery, and the
      results evaluated using radiodensitometric and histological studies; they were
      also examined histomorphometrically. When the calcium phosphate glass powders
      with 400-microm particles were grafted, the defects were nearly completely filled
      with new-formed bone in a clean healing condition after 8 weeks. It was observed
      that the prepared calcium phosphate glass enhanced new bone formation in the
      calvarial defect of Sprague-Dawley rats and could be expected to have potential
      for use as a hard tissue regeneration material.

PMID- 15983996
TI  - Frequent coexpression of the vesicular glutamate transporter 1 and 2 genes, as
      well as coexpression with genes for choline acetyltransferase or glutamic acid
      decarboxylase in neurons of rat brain.
AB  - It is widely believed that expression of the vesicular glutamate transporter
      genes VGLUT1 and VGLUT2 is restricted to glutamatergic neurons and that the two
      transporters segregate in different sets of neurons. Using single-cell multiplex
      RT-PCR (sc-RT-mPCR), we show that VGLUT1 and VGLUT2 mRNAs were coexpressed in
      most of the sampled neurons from the rat hippocampus, cortex, and cerebellum at
      postnatal Day (P)14 but not P60. In accordance, changes in VGLUT1 and VGLUT2 mRNA
      concentrations were found to occur in these and other brain areas between P14 and
      P60, as revealed by semiquantitative RT-PCR and quantitated by ribonuclease
      protection assay. VGLUT1 and -2 coexpression in the hippocampal formation is
      supported further by in situ hybridization data showing that virtually all cells
      in the CA1-CA3 pyramidal and granule cell layers were highly positive for both
      transcripts until P14. It was revealed using sc-RT-mPCR that transcripts for
      VGLUT1 and VGLUT2 were also present in neurons of the cerebellum, striatum, and
      septum that expressed markers for gamma-aminobutyric acid (GABA)ergic or
      cholinergic phenotypes, as well as in hippocampal cells containing transcripts
      for the glial fibrillary acidic protein. Our study suggests that VGLUT1 and
      VGLUT2 proteins may often transport glutamate into vesicles within the same
      neuron, especially during early postnatal development, and that they are
      expressed widely in presumed glutamatergic, GABAergic, and cholinergic neurons,
      as well as in astrocytes. Furthermore, our study shows that such coexpressing
      neurons remain in the adult brain and identifies several areas that contain them
      in both young and adult rats.

PMID- 15983997
TI  - Gi/Go protein-dependent presynaptic mechanisms are involved in clozapine-induced
      down-regulation of tyrosine hydroxylase in PC12 cells.
AB  - Although the clinical effects of antipsychotics have been extensively studied,
      the molecular mechanisms underlying their antipsychotic activity are unclear.
      Chronic clozapine has been reported to reduce significantly the expression of
      tyrosine hydroxylase (TH) in the mesolimbic system. To characterize the
      mechanisms of action of clozapine on TH expression, PC12 cells turned out to be a
      useful model, being by far less complex than the entire brain. Both the quantity
      of TH protein and the amount of TH mRNA in PC12 cells were found to be decreased
      during incubation of the cells in the presence of clozapine. This decline was
      followed by a decrease in the enzymatic activity of TH. The effect of clozapine
      was blocked by preincubation with N-ethylmaleimide, a sulphydryl-alkylating
      reagent that interferes in Gi/o protein-mediated second messenger pathways.
      Clozapine may thus decrease TH expression by interacting with Gi/o protein
      coupled receptors, such as D2 and 5HT1A. Knowledge of the molecular mechanisms
      underlying the clinical effects of established antipsychotics will promote the
      development of new and more efficient antipsychotic drugs.

PMID- 15983999
TI  - Differential distribution of release-related proteins in the hippocampal CA3 area
      as revealed by freeze-fracture replica labeling.
AB  - Synaptic vesicle release occurs at a specialized membrane domain known as the
      presynaptic active zone (AZ). Several membrane proteins are involved in the
      vesicle release processes such as docking, priming, and exocytotic fusion.
      Cytomatrix at the active zone (CAZ) proteins are structural components of the AZ
      and are highly concentrated in it. Localization of other release-related proteins
      including target soluble N-ethylmaleimide-sensitive-factor attachment protein
      receptor (t-SNARE) proteins, however, has not been well demonstrated in the AZ.
      Here, we used sodium dodecyl sulfate-digested freeze-fracture replica labeling
      (SDS-FRL) to analyze quantitatively the distribution of CAZ and t-SNARE proteins
      in the hippocampal CA3 area. The AZ in replicated membrane was identified by
      immunolabeling for CAZ proteins (CAZ-associated structural protein [CAST] and
      Bassoon). Clusters of immunogold particles for these proteins were found on the P
      face of presynaptic terminals of the mossy fiber and associational/commissural
      (A/C) fiber. Co-labeling with CAST revealed distribution of the t-SNARE proteins
      syntaxin and synaptosomal-associated protein of 25 kDa (SNAP-25) in the AZ as
      well as in the extrasynaptic membrane surrounding the AZ (SZ). Quantitative
      analysis demonstrated that the density of immunoparticles for CAST in the AZ was
      more than 100 times higher than in the SZ, whereas that for syntaxin and SNAP-25
      was not significantly different between the AZ and SZ in both the A/C and mossy
      fiber terminals. These results support the involvement of the t-SNARE proteins in
      exocytotic fusion in the AZ and the role of CAST in specialization of the
      membrane domain for the AZ.

PMID- 15983998
TI  - Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma.
AB  - Acoustic injury results in destruction of hair cells and numerous nonsensory
      cells of the cochlea. How these injured structures undergo repair is not well
      understood. This study was designed to examine the cochlea for the presence of
      mononuclear phagocytes after tissue injury caused by noise damage. We used octave
      band noise (8--16 kHz) at three levels (106, 112, and 120 dB) for 2 hours and
      studied the mice at 1, 3, 7, and 14 days after noise exposure to determine how
      noise affected hearing thresholds, hair cell number, and tissue injury in the
      cochlea. Furthermore, we assessed the cochlea for presence of inflammation by
      performing immunohistochemistry for CD45, common leukocyte antigen. We counted
      the number of CD45(+) cells that were present in the cochlea at the above
      mentioned time points after noise. CD45 is present on all bone marrow-derived
      white blood cells and is not otherwise expressed in the inner ear. We found that,
      after noise exposure, there is a large increase in CD45(+) cells. These marrow
      derived cells are concentrated in the spiral ligament and spiral limbus, areas
      that are known to be susceptible to acoustic injury. It is possible that this
      inflammatory response plays a role in propagating cellular damage in these areas.
      Immunohistochemistry demonstrates that these cochlear cells are derived from the
      monocyte/macrophage lineage and serve a phagocytic function in the inner ear.

PMID- 15984000
TI  - Cortical influences on sizes and rapid plasticity of tactile receptive fields in
      the dorsal column nuclei.
AB  - The cerebral cortex influences subcortical processing. In the somatosensory
      system, descending cortical inputs contribute in specific ways to the sizes and
      plasticity of tactile receptive fields (RFs) in the thalamus, but less is known
      about cortical influences on these aspects of brainstem RFs. The present studies
      evaluated how loss of cortical inputs affects sizes and plasticity of RFs in the
      brainstem dorsal column nuclei (DCN) when peripheral inputs were normal and when
      peripheral inputs were acutely disrupted. Loss of cortical inputs was produced by
      acute lesion of somatosensory, motor, and adjacent cortex, whereas disruption of
      peripheral inputs was produced by cutaneous microinjection of lidocaine (LID).
      Modest or no changes in sizes of DCN RFs, comparable to changes during control
      periods of no treatment, were seen in response to cortical lesion. LID caused
      rapid enlargements in RFs when cortex was intact. LID also caused rapid RF
      enlargements after cortical lesion, and these enlargements were greater than post
      LID enlargements when cortex was intact. These results indicate that normally
      sized RFs continue to be produced in the DCN after loss of cortical input. Cortex
      is also not required for RF enlargements after LID; however, cortical inputs have
      a constraining effect on these enlargements. Considered with findings from
      previous thalamic studies, these results suggest that cortical influences on RF
      size and plasticity in the DCN and thalamus differ in some respects.

PMID- 15984001
TI  - Changes in the density and distribution of sympathetic nerves in spleens from
      Lewis rats with adjuvant-induced arthritis suggest that an injury and sprouting
      response occurs.
AB  - Previously we demonstrated reduced norepinephrine concentrations in spleens from
      Lewis rats with adjuvant-induced arthritis (AA), an animal model of rheumatoid
      arthritis. This study extends these findings, examining the anatomical
      localization and density of sympathetic nerves in the spleen with disease
      development. Noradrenergic (NA) innervation in spleens of Lewis rats was examined
      28 days following adjuvant treatment to induce arthritis or vehicle for the
      adjuvant by using fluorescence histochemistry for catecholamines, with
      morphometric analysis and immunocytochemistry for tyrosine hydroxylase. In AA
      rats, sympathetic nerve density in the hilar regions, where NA nerves enter the
      spleen, was increased twofold over that observed in vehicle-treated rats. In
      contrast, there was a striking twofold decline in the density of NA nerves in
      splenic regions distal to the hilus in arthritic rats compared with nonarthritic
      rats. In both treatment groups, NA nerves distributed to central arterioles,
      white pulp regions, trabeculae, and capsule. However, NA nerve density was
      reduced in the white pulp but was increased in the red pulp in AA rats compared
      with non-AA rats. These findings indicate an injury/sprouting response with
      disease development whereby NA nerves die back in distal regions and undergo a
      compensatory sprouting response in the hilus. The redistribution of NA nerves
      from white pulp to red pulp suggests that these nerves signal activated immune
      cells localized in the red pulp in AA. Although the mechanisms of this
      redistribution of NA nerves into the red pulp are not known, it may be due to
      migration from white pulp to red pulp of target immune cells that provide trophic
      support for these nerves. The redistribution of NA nerves into the red pulp may
      be critical in modulating immune functions that contribute to the chronic
      inflammatory stages of arthritis.

PMID- 15984002
TI  - Distribution of synaptic zinc in the macaque monkey amygdala.
AB  - We have mapped the macaque amygdala for the distribution of synaptic zinc (Zn), a
      co-factor of glutamate implicated in plasticity, as well as in several
      excitotoxic and other pathophysiological conditions. In brief, we found that the
      amygdala is Zn enriched in all nuclear groups (i.e., basolateral and cortical
      groups, as well as central and medial nuclei) but with marked differences in
      density. By comparing parallel tissue series histologically reacted for Zn and
      parvalbumin (PV), we further found that regions high in Zn are typically low in
      PV neuropil. In the basolateral group, there is a particularly distinct
      dorsoventral gradation such that Zn levels are most dense ventrally, i.e., in the
      paralaminar nucleus, the ventral division of the lateral nucleus, and the
      parvicellular divisions of both the basal nucleus and the accessory basal
      nucleus. PV levels are least dense in these same regions. For the central and
      medial nuclei, there is a slight mediolateral gradient, with Zn levels being
      higher medially. PV is low overall in these nuclei. Electron microscopic results
      confirmed that Zn is contained in synaptic boutons. These form asymmetrical,
      presumably excitatory, synapses, and the postsynaptic targets are mainly spines
      of projection neurons. The inhomogeneous distribution of Zn in the monkey
      amygdala may be related to different types or degrees of plasticity among the
      amygdaloid subnuclei. The complementary distribution with PV parallels that of
      several other substances and is interesting in the context of subnuclear
      vulnerability for human neuronal disease, such as seizure and Alzheimer's
      disease.

PMID- 15984003
TI  - Neuropeptide Y in the forebrain of the adult male cichlid fish Oreochromis
      mossambicus: distribution, effects of castration and testosterone replacement.
AB  - We studied the organization of the neuropeptide Y (NPY)-immunoreactive system in
      the forebrain of adult male cichlid fish Oreochromis mossambicus and its response
      to castration and testosterone replacement by using morphometric methods.
      Immunoreactivity for NPY was widely distributed in the forebrain, and the pattern
      generally resembled that in other teleosts. Whereas immunoreactivity was
      conspicuous in the ganglia of nervus terminalis (NT; or nucleus
      olfactoretinalis), a weak reaction was detected in some granule cells in the
      olfactory bulb and in the cells of area ventralis telencephali pars lateralis
      (Vl). Moderately to intensely immunoreactive cells were distinctly seen in the
      nucleus entopeduncularis (NE), nucleus preopticus (NPO), nucleus lateralis
      tuberis (NLT), paraventricular organ (PVO), and midbrain tegmentum (MT). NPY
      fibers were widely distributed in the forebrain. Castration for 10/15 days
      resulted in a drastic loss of immunoreactivity in the cells of NE (P<0.001) and a
      significant decrease (P<0.01) in their cell nuclear size. However, cell nuclei of
      the NT neurons showed a significant increase in size. A highly significant
      reduction in the NPY-immunoreactive fiber density (P<0.001) was observed in
      several areas of the forebrain. Although testosterone replacement reversed these
      changes, fibers in some areas showed supranormal responses. Immunoreactive cells
      in Vl, NPO, NLT, PVO, and MT and fiber density in some other areas did not
      respond to castration. We suggest that the NPY-immunoreactive elements that
      respond to castration and testosterone replacement may serve as the substrate for
      processing the positive feedback action of the steroid hormone.

PMID- 15984005
TI  - Comparative anatomy of alpha(2) and beta adrenoceptors in the adult and
      developing brain of the marine teleost the red porgy (Pagrus pagrus, Sparidae):
      [(3)H]clonidine and [(3)H]dihydroalprenolol quantitative autoradiography and
      receptor subtypes immunohistochemistry.
AB  - The present study aimed to determine the anatomic distribution and developmental
      profile of alpha(2) and beta adrenoceptors (AR) in marine teleost brain. Alpha 2
      and beta adrenoceptors were studied at different developmental stages by using
      [(3)H]clonidine and [(3)H]dihydroalprenolol, respectively, by means of in vitro
      quantitative autoradiography. Furthermore, immunohistochemical localization of
      the receptor subtypes was performed to determine their cellular distribution.
      Saturation studies determined a high-affinity component of [(3)H]clonidine and
      [(3)H]dihydroalprenolol binding sites. High levels of both receptors were found
      in preglomerular complex, ventral hypothalamus, and lateral torus. Dorsal
      hypothalamus and isthmus included high levels of alpha(2) AR, whereas pretectum
      and molecular and proliferative zone of cerebellum were specifically
      characterized by high densities of beta AR. From the first year of life, adult
      levels of both AR were found in most medial telencephalic, hypothalamic, and
      posterior tegmental areas. Decreases in both receptors densities with age were
      prominent in ventral and posterior telencephalic, pretectal, ventral thalamic,
      hypothalamic, and tegmental brain regions. Immunohistochemical data were well
      correlated with autoradiography and demonstrated the presence of alpha(2A),
      alpha(2C), beta(1), and beta(2) AR subtype-like immunoreactivity. Both the
      neuronal (perikaryal or dendritic) and the glial localization of receptors was
      revealed. The localization and age-dependent alterations in alpha(2) and beta AR
      were parallel to plasticity mechanisms, such as cell proliferation in
      periventricular thalamus, hypothalamus, and cerebellum. In addition, the
      biochemical characteristics, distribution pattern, and neuronal or glial
      specificity of the receptors in teleost brain support a similar profile of
      noradrenergic transmission in vertebrate brain evolution.

PMID- 15984004
TI  - Estrogen regulation of cell proliferation and distribution of estrogen receptor
      alpha in the brains of adult female prairie and meadow voles.
AB  - Adult female prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) voles
      were compared to examine neural cell proliferation and the effects of estrogen
      manipulation on cell proliferation in the amygdala, ventromedial hypothalamus
      (VMH), and dentate gyrus of the hippocampus (DG). Unlike prior studies, our study
      focused on the amygdala and VMH, because they are involved in social behaviors
      and may underlie behavioral differences between the species. Meadow voles had a
      higher density of cells labeled with the cell proliferation marker 5-bromo-2'
      deoxyuridine (BrdU) in the amygdala and DG than did prairie voles. Treatment with
      estradiol benzoate (EB) for 3 days increased the density of BrdU-labeled cells in
      the amygdala, particularly in the posterior cortical (pCorA) and medial (pMeA)
      nuclei, in meadow, but not prairie, voles. Furthermore, the majority of the BrdU
      labeled cells in the pCorA and pMeA displayed either a neuronal or a glial
      progenitor phenotype, but no species or treatment differences were found in the
      percentage of neuronal or glial progenitor cells. To understand better estrogen's
      effects on adult neurogenesis, we also examined estrogen receptor-alpha (ERalpha)
      distribution. Meadow voles had more ERalpha-labeled cells in the pCorA and VMH,
      but not in the pMeA or DG, than did prairie voles. In addition, more than one
      half of the BrdU-labeled cells in the amygdala of both species coexpressed
      ERalpha labeling. Together, these data indicate that estrogen alters cell
      proliferation in a species- and region-specific manner, and some of these effects
      may lie in the specific localization of estrogen receptors in the adult vole
      brain.

PMID- 15984006
TI  - Schwann cell behavior after nerve repair by means of tissue-engineered muscle
      vein combined guides.
AB  - Schwann cells play a critical role in peripheral nerve regeneration. When a non
      nervous conduit is used to bridge a nerve defect, the conduit is soon colonized
      by a number of Schwann cells that make a pathway for regrowing axons. By using
      electron microscopy, immunohistochemistry, and reverse transcriptase-polymerase
      chain reaction analysis, we have investigated the behavior of migratory glial
      cells along a particular type of autologous tissue-engineered conduit made of a
      vein filled with fresh skeletal muscle, using the rat sciatic nerve model. With
      this particular type of autograft, our data show that many Schwann cells soon
      take up a close relationship with grafted muscle fibers, and especially with
      their basal lamina, which appears to serve as a migration pathway for them. The
      early and massive colonization of the conduit is sustained by both Schwann cell
      migration and proliferation, as demonstrated by PCNA immunostaining. Later, as
      they meet regenerating axons, Schwann cells become closely associated with them
      and eventually lose their connections with grafted muscle fibers because of the
      formation of perineurial envelopes. Because previous studies showed that alpha(2a
      2b) NRG1 is overexpressed at early stages along the muscle-vein combined tubes,
      we have also investigated mRNA expression of its two receptors, erbB2 and erbB3.
      Both messengers are overexpressed, although with different time courses. Overall,
      our results provide some morphological and biochemical bases for explaining the
      effectiveness of fresh muscle-vein combined nerve guides and throw an interesting
      light on the possible role of alpha(2a-2b) NRG1 through the erbB2/erbB3
      heterodimer receptor for nerve regeneration inside non-nervous conduits.

PMID- 15984008
TI  - Dopaminergic influences on formation of a motor memory.
AB  - The ability of the central nervous system to form motor memories, a process
      contributing to motor learning and skill acquisition, decreases with age.
      Dopaminergic activity, one of the mechanisms implicated in memory formation,
      experiences a similar decline with aging. It is possible that restoring
      dopaminergic function in elderly adults could lead to improved formation of motor
      memories with training. We studied the influence of a single oral dose of
      levodopa (100mg) administered preceding training on the ability to encode an
      elementary motor memory in the primary motor cortex of elderly and young healthy
      volunteers in a randomized, double-blind, placebo-controlled design. Attention to
      the task and motor training kinematics were comparable across age groups and
      sessions. In young subjects, encoding a motor memory under placebo was more
      prominent than in older subjects, and the encoding process was accelerated by
      intake of levodopa. In the elderly group, diminished motor memory encoding under
      placebo was enhanced by intake of levodopa to levels present in younger subjects.
      Therefore, upregulation of dopaminergic activity accelerated memory formation in
      young subjects and restored the ability to form a motor memory in elderly
      subjects; possible mechanisms underlying the beneficial effects of dopaminergic
      agents on motor learning in neurorehabilitation.

PMID- 15984009
TI  - Renin-angiotensin-aldosterone system in brain infarction and vascular death.
AB  - The renin-angiotensin-aldosterone system has functions that may contribute to
      brain infarction (BI). In 459 matched pairs of white patients and control
      subjects, we measured plasma angiotensin-converting enzyme (ACE) levels, seven
      polymorphisms (angiotensinogen T174M and M235T, ACE I/D and 4656 2/3CT repeat
      [rpt], angiotensin II type 1 receptor A1166C and A153G, and aldosterone synthase
      CYP11B2), and evaluated 5-year poststroke mortality. Mean plasma ACE levels (+/
      standard error) were significantly greater in patients than control subjects
      (37.5 +/- 0.9 vs 33.9 +/- 0.9), in patients with lacunar stroke, and in patients
      with no previous vascular (cerebrovascular or cardiovascular) history. The risk
      for BI increased with tertiles of plasma ACE, without an interaction with
      hypertension. After adjustments, the association disappeared except among
      patients with cardioembolic BI and those without previous vascular events. Among
      the polymorphisms, there was a weak association of BI with angiotensin II type 1
      receptor 1166C, a weak protective effect with angiotensinogen 174M, and a strong
      association of angiotensinogen 235T with 5-year vascular mortality. These results
      suggest that renin-angiotensin-aldosterone system activity and genes contribute
      to cerebrovascular disease and poststroke vascular death in white patients.

PMID- 15984010
TI  - Amyloid beta 38, 40, and 42 species in cerebrospinal fluid: more of the same?
AB  - Various C-terminally truncated amyloid beta peptides (Abeta) are linked to
      Alzheimer's disease (AD) pathogenesis. Cerebrospinal fluid (CSF) concentrations
      of Abeta38, Abeta40, and Abeta42 were measured by enzyme-linked immunosorbent
      assay in 30 patients with AD and 26 control subjects. CSF Abeta42 levels was
      decreased in patients with AD, whereas CSF Abeta38 and Abeta40 levels were
      similar in patients with AD and control subjects. All three Abeta peptides were
      interrelated, particularly CSF Abeta38 and Abeta40. Diagnostic accuracy of CSF
      Abeta42 concentrations was not improved by applying the ratios of CSF Abeta42 to
      Abeta38 or Abeta40.

PMID- 15984011
TI  - Brain activation in offspring of AD cases corresponds to 10q linkage.
AB  - Previously, we reported evidence of genetic heterogeneity in late-onset familial
      Alzheimer's disease, based on sex of affected parent, demonstrating linkage to
      chromosome 10q, a region identified by other groups and implicated as a
      quantitative trait loci for Abeta levels, in families with an affected mother.
      Using functional magnetic resonance imaging and a memory encoding task, we now
      show differential brain activation patterns among asymptomatic offspring which
      correspond to the previous linkage finding. These results suggest the possibility
      that activation patterns may prove useful as a preclinical quantitative trait
      related to the putative familial late-onset AD gene in this chromosome 10 region.

PMID- 15984012
TI  - Amyloid-beta oligomers are inefficiently measured by enzyme-linked immunosorbent
      assay.
AB  - Amyloid-beta (Abeta) peptide levels are widely measured by enzyme-linked
      immunosorbent assay (ELISA) in Alzheimer's disease research. Here, we show that
      oligomerization of Abeta results in underestimated Abeta ELISA levels. The
      implications are that comprehensive analysis of soluble Abeta requires either
      sample pretreatment at denaturing conditions or novel conformation-dependent
      immunoassays. Our findings might be of relevance for many neurodegenerative
      disorders in which soluble protein aggregates are the main neurotoxic species.

PMID- 15984016
TI  - Mental retardation and ataxia due to normotriglyceridemic
      hypobetalipoproteinemia.
AB  - A 12-year-old boy with mental retardation, obesity, ataxia, and visual impairment
      was shown to have normal fasting plasma triglyceride but low cholesterol and
      vitamin E levels. Investigations indicated that he was compound heterozygous for
      two mutations in the apolipoprotein B gene (APOB), resulting in a failure to
      express apolipoprotein B-100, yet retain apolipoprotein B-48 production. The
      proband therefore was able to form chylomicrons, but not a low-density
      lipoprotein capable of receptor-mediated endocytosis. This resulted in chronic
      vitamin E deficiency. We suggest the term normotriglyceridemic
      hypobetalipoproteinemia for this easily recognizable condition.

PMID- 15984018
TI  - Calculating total electrical energy delivered by deep brain stimulation systems.

PMID- 15984017
TI  - 6-pyruvoyl-tetrahydropterin synthase deficiency with mild hyperphenylalaninemia.
AB  - Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a
      tetrahydrobiopterin deficiency disorder that presents in infancy with
      developmental delay, seizures, and abnormal movements associated with
      hyperphenylalaninemia usually detectable by neonatal phenylketonuria screening
      programs. We describe an 8-year-old girl with delay, seizures, and dystonia with
      mild hyperphenylalaninemia detected in late childhood. The diagnosis of 6
      pyruvoyl-tetrahydrobiopterin synthase deficiency was made by analysis of pterins
      in urine, pterins and neurotransmitters in cerebrospinal fluid, and enzyme assay.
      The patient improved clinically taking oral tetrahydrobiopterin,
      levodopa/carbidopa, and 5-hydroxytryptophan. This treatable condition may not
      always be detected by routine population screening for hyperphenylalaninemia.

PMID- 15984019
TI  - Increased brain concentrations of a neuroinhibitory steroid in human hepatic
      encephalopathy.

PMID- 15984021
TI  - CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular
      dystrophy.
AB  - We tested the efficacy and safety of glutamine (0.6 gm/kg/day) and creatine (5
      gm/day) in 50 ambulant boys with Duchenne muscular dystrophy in a 6-month, double
      blind, placebo-controlled clinical trial. Drug efficacy was tested by measuring
      muscle strength manually (34 muscle groups) and quantitatively (10 muscle
      groups). Timed functional tests, functional parameters, and pulmonary function
      tests were secondary outcome measures. Although there was no statistically
      significant effect of either therapy based on manual and quantitative
      measurements of muscle strength, a disease-modifying effect of creatine in older
      Duchenne muscular dystrophy and creatine and glutamine in younger Duchenne
      muscular dystrophy cannot be excluded. Creatine and glutamine were well
      tolerated.

PMID- 15984025
TI  - A new hypothesis for dystonia.

PMID- 15984022
TI  - A 10-item smell identification scale related to risk for Alzheimer's disease.
AB  - University of Pennsylvania Smell Identification Test data from control subjects
      (n = 63), patients with mild cognitive impairment (n = 147), and patients with
      Alzheimer's disease (n = 100) were analyzed to derive an optimal subset of items
      related to risk for Alzheimer's disease (ie, healthy through mild cognitive
      impairment to early and moderate disease stages). The derived 10-item scale
      performed comparably with the University of Pennsylvania Smell Identification
      Test in classifying subjects, and it strongly predicted conversion to Alzheimer's
      disease on follow-up evaluation in patients with mild cognitive impairment.
      Independent replication is needed to validate these findings.

PMID- 15984026
TI  - Electroencephalographic response to transcranial magnetic stimulation in
      children: Evidence for giant inhibitory potentials.
AB  - The electroencephalographic response to transcranial magnetic stimulation (TMS)
      recently has been established as a direct parameter of motor cortex excitability.
      Its N100 component was suggested to reflect an inhibitory response. We
      investigated influences of cerebral maturation on TMS-evoked N100 in 6- to 10
      year-old healthy children. We used a forewarned reaction time (contingent
      negative variation) task to test the effects of response preparation and sensory
      attention on N100 amplitude. Single-pulse TMS of motor cortex at 105% motor
      threshold intensity evoked N100 amplitudes of more than 100 microV in resting
      children (visible in single trials), which correlated negatively with age and
      positively with absolute stimulation intensity. During late contingent negative
      variation, which involves preactivation of the cortical structures necessary for
      a fast response, N100 amplitude was significantly reduced. We conclude that (1)
      N100 amplitude reduction during late contingent negative variation provides
      further evidence that TMS-evoked N100 reflects inhibitory processes, (2) response
      preparation and attention modulate N100, and (3) TMS-evoked N100 undergoes
      maturational changes and could serve to test cortical integrity and inhibitory
      function in children. Parallels between the inhibitory N100 after TMS (provoking
      massive synchronous excitation) and the inhibitory wave component of epileptic
      spike wave complexes are suggested.

PMID- 15984027
TI  - Pre-existing hypertension and the impact of stroke on cognitive function.
AB  - Hypertension has been associated with subclinical injury in the brain and may
      therefore increase the impact of an incident stroke on cognitive function. The
      Study of Osteoporotic Fractures (SOF) is a prospective, observational study of
      9,704 women aged 65 years and older recruited from four U.S. metropolitan areas.
      Blood pressure was measured at study entry, and cognitive decline was defined by
      the change from prestroke to poststroke cognitive testing. During an average
      follow-up of 6.8 years, incident stroke occurred in 260 participants (3.1%) who
      had previously completed baseline cognitive testing. Among participants with
      stroke, 119 completed follow-up cognitive testing a median of 1.9 years after the
      stroke, 80 died before the next study visit, and 61 did not complete further
      cognitive testing. After adjustment for demographic factors and other
      confounders, pre-existing hypertension was a strong predictor of cognitive
      decline when a stroke occurred (odds ratio [OR], 4.07; 95% confidence interval
      [CI], 1.37-12.1). In contrast, hypertension was only weakly associated with
      cognitive decline in the absence of stroke (OR, 1.13; 95% CI, 1.04-1.22) (p for
      interaction = 0.032). Pre-existing hypertension in women is associated with a
      greater impact of stroke on cognitive function, possibly by influencing the
      ability to tolerate or recover from brain injury.

PMID- 15984028
TI  - Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia.
AB  - Hypothermia after perinatal hypoxia-ischemia (HI) is neuroprotective; the precise
      brain temperature that provides optimal protection is unknown. To assess the
      pattern of brain injury with 3 different rectal temperatures, we randomized 42
      newborn piglets: (Group i) sham-normothermia (38.5-39 degrees C); (Group ii) sham
      33 degrees C; (Group iii) HI-normothermia; (Group iv) HI-35 degrees C; and (Group
      v) HI-33 degrees C. Groups iii through v were subjected to transient HI insult.
      Groups ii, iv, and v were cooled to their target rectal temperatures between 2
      and 26 hours after resuscitation. Experiments were terminated at 48 hours.
      Compared with normothermia, hypothermia at 35 degrees C led to 25 and 39%
      increases in neuronal viability in cortical gray matter (GM) and deep GM,
      respectively (both p < 0.05); hypothermia at 33 degrees C resulted in a 55%
      increase in neuronal viability in cortical GM (p < 0.01) but no significant
      increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33
      degrees C, 35 degrees C resulted in more viable neurons in deep GM, whereas 33
      degrees C resulted in more viable neurons in cortical GM (both p < 0.05). These
      results suggest that optimal neuroprotection by delayed hypothermia may occur at
      different temperatures in the cortical and deep GM. To obtain maximum benefit,
      you may need to design patient-specific hypothermia protocols by combining
      systemic and selective cooling.

PMID- 15984029
TI  - The touch dome in human skin is supplied by different types of nerve fibers.
AB  - Receptor end organs and free-nerve endings in the skin are the peripheral
      sentinels of the sensorial nervous system encoding for touch, temperature, and
      pain. Using a novel approach to analyze the outermost nerves of the skin, we
      visualized for the first time the distinct microanatomical structure of the touch
      dome of human hairy skin. The dermal nerve fibers of this slowly adapting type 1
      mechanoreceptor were embedded in dermal protrusions that could be readily
      discerned by Laminin-5 staining. Concerning the nerves supplying the touch domes,
      we found, unexpectedly, that besides Abeta-fibers, Adelta- and C-fibers also were
      regularly present. The epidermis overlying the nerve convolutes showed a
      distinctive architecture of the rete ridges clearly demarcated from the
      surroundings and extending over 0.193 +/- 0.138 mm(2) (mean +/- standard
      deviation). Within this area, 756 +/- 386 Merkel cells/mm(2) (mean +/- standard
      deviation) were present compared with less than 50/mm(2) outside the touch dome,
      demonstrating for the first time a highly discontinuous distribution of these
      cells in nonglabrous skin. Our findings strongly suggest that the receptive
      qualities of human touch domes exceed mechanosensation, and that they may serve
      as multifunctional nerve end organs in human skin.

PMID- 15984030
TI  - Amphiphysin autoimmunity: paraneoplastic accompaniments.
AB  - Amphiphysin-IgG was identified in 71 patients among 120,000 evaluated
      serologically for paraneoplastic autoantibodies. Clinical information was
      available for 63 patients. Cancer was detected in 50 (mostly limited), proven
      histologically in 46, and was imaged intrathoracically in 4 patients (lung, small
      cell [27] and non-small cell [1]), breast [16] and melanoma [2]). Neurological
      accompaniments included (decreasing frequency): neuropathy, encephalopathy,
      myelopathy, stiff-man phenomena, and cerebellar syndrome. In a case examined
      neuropathologically, parenchymal T-lymphocyte infiltration (predominantly CD8(+))
      was prominent in lower brainstem, spinal cord, and dorsal root ganglion.
      Coexisting paraneoplastic autoantibodies, identified in 74% of patients,
      predicted a common neoplasm and indicated other neuronal autoantigen targets that
      plausibly explained several neurological manifestations; for example, P/Q-type
      Ca(2+)-channel antibody with Lambert-Eaton syndrome (n = 5), anti-neuronal
      nuclear antibody type 1 with sensory neuronopathy (n = 7), K(+)-channel antibody
      with limbic encephalitis (n = 1) or neuromyotonia (n = 1), and collapsin response
      mediator protein-5-IgG with optic neuritis (n = 3). Patients with isolated
      amphiphysin-IgG (n = 19) were more likely to be women (with breast cancer, p <
      0.05) and to have myelopathy or stiff-man phenomena (p < 0.01). Overall, a
      minority of women (39%) and men (12%) had stiff-man phenomena. Only 10% of women
      (some with lung carcinoma) and 4% of men fulfilled diagnostic criteria for stiff
      man syndrome.

PMID- 15984031
TI  - Selective vulnerability of preterm white matter to oxidative damage defined by F2
      isoprostanes.
AB  - Periventricular white matter injury (PWMI) is the leading cause of cerebral palsy
      and chronic neurological disability in survivors of prematurity. Despite the
      large number of affected children, the pathogenetic mechanisms related to PWMI
      remain controversial. Through studies of 33 human autopsy brains, we determined
      that early PWMI was related to oxidative damage that particularly targeted the
      oligodendrocyte lineage, whereas other neuronal and glial cell types were
      markedly more resistant. F(2)-isoprostanes, an arachidinate metabolite/lipid
      peroxidation marker of oxidative damage, were significantly increased in early
      PWMI lesions but not in cerebral cortex. That deleterious lipid peroxidation
      accompanied early PWMI was supported by similar increases in F(2)-isoprostanes
      levels in the cerebral cortex from term infants with hypoxic-ischemic cortical
      injury. Detection of F(4)-neuroprostanes, a neuronal-specific oxidative damage
      marker, confirmed that neuroaxonal elements were resistant to injury in cerebral
      cortex and white matter. Significant protein nitration was not detected in PWMI
      lesions by 3-nitrotyrosine staining. Significant cellular degeneration was
      confirmed in early PWMI lesions by terminal deoxynucleotidyltransferase-mediated
      dUTP nick end labeling and a marked depletion of oligodendrocyte progenitors of
      71 +/- 8%. Hence, the predilection of preterm infants for PWMI is related to
      selective lipid peroxidation-mediated injury of cerebral white matter and
      targeted death of oligodendrocyte progenitors.

PMID- 15984033
TI  - Application of model discriminating experimental design for modeling and
      development of a fermentative fed-batch L-valine production process.
AB  - A model discriminating experimental design approach for fed-batch processes has
      been developed and applied to the fermentative production of L-valine by a
      genetically modified Corynebacterium glutamicum strain possessing multiple
      auxotrophies as an example. Being faced with the typical situation of uncertain
      model information based on preliminary experiments, model discriminating design
      was successfully applied to improve discrimination between five competing models.
      Within the same modeling and experimental design framework, also the planning of
      an optimized production process with respect to the total volumetric productivity
      is shown. Simulation results were experimentally affirmed, yielding an increased
      total volumetric productivity of 6.2 mM L-valine per hour. However, also so far
      unknown metabolic mechanisms were observed in the optimized process, underlining
      the importance of process optimization during modeling to avoid problems of
      extreme extrapolation of model predictions during the final process optimization.

PMID- 15984034
TI  - Broadening the insecticidal spectrum of Lepidoptera-specific Bacillus
      thuringiensis strains by chromosomal integration of cry3A.
AB  - A TnpI-TnpIA-mediated and thermosensitive recombination system was developed to
      construct genetically modified Bacillus thuringiensis strains encoding a crystal
      protein particularly active against Coleopteran species. Based on B.
      thuringiensis transposon Tn4430, an integrative vector, pBMB-R14E, was
      constructed, by which the cry3A delta-endotoxin gene highly toxic to Lepidoptera
      was delivered into a wildtype B. thuringiensis subsp. kurstaki strain YBT1520.
      The cry3A gene was integrated into the chromosome of the host strain. Then the
      integrative vector was eliminated by moving recombinant cultures to 46 degrees C.
      Two recombinant B. thuringiensis strains, BMB1520-S and BMB1520-T, were obtained.
      In recombinant strains, the cry3A gene was stably expressed in measurable amounts
      and did not reduce the expression of endogenous crystal protein genes. Bioassay
      results showed that BMB1520-S and BMB1520-T, in addition to the activity against
      lepidopteran Plutella xylostella third-instar larvae present in the parental
      strains, exhibited a high level of activity against coleopteran Rhyllodecta
      vulgatissima third-instar larvae, absent from the parental strains.

PMID- 15984035
TI  - Determinants of embolic protection device use: case study in the acceptance of a
      new medical technology.

PMID- 15984037
TI  - Absolute asymmetric synthesis of stereochemically labile aldehyde helicates and
      subsequent chirality transfer reactions.
AB  - Helical complexes formed between aluminum tris(2,6-diphenylphenoxide) (ATPH) and
      five different aldehydes have been prepared and structurally characterized by X
      ray diffraction. It was found that [Al(OC6H3Ph2)3PhCHO] (2), [Al(OC6H3Ph2)3(4
      CH3C6H4CHO)] (3), [Al(OC6H3Ph2)3(4-tBuC6H4CHO)] (4), and [Al(OC6H3Ph2)3(p
      CH3OC6H4CHO)] (5) all crystallize as conglomerates, while crystals of
      [Al(OC6H3Ph2)3(o-CH3OC6H4CHO)] (6) are racemic. Supramolecular CH/pi interactions
      between molecules in crystals of 2-5 that enable stereochemical information to be
      mediated in three dimensions have been identified and explain the high frequency
      of conglomerate formation among ATPH helicates. Since 2-5 are stereochemically
      labile and thus enantiomerize rapidly in solution, the conglomerates can be
      resolved by crystallization-induced asymmetric transformation. The determination
      of the enantiomeric excess (ee) in solid samples of stereochemically labile
      molecules is not trivial, but solid-state CD spectroscopic data, anomalous
      dispersion data, and the ee values in alkylation reactions all indicate that
      preferential crystallization of 2-5 yields an essentially enantiopure product.
      Thus the preparation of 2-5 constitute new examples of absolute asymmetric
      synthesis. The helical chirality can be transferred (and thus trapped) to
      alcohols (with ee values of up to 16%) in crystal-to-crystal reactions with
      achiral organometallic reagents.

PMID- 15984036
TI  - Molecular recognition of aminoglycoside antibiotics by bacterial defence
      proteins: NMR study of the structural and conformational features of streptomycin
      inactivation by Bacillus subtilis aminoglycoside-6-adenyl transferase.
AB  - The molecular recognition of streptomycin by Bacillus subtilis aminoglycoside-6
      adenyl transferase has been analysed by a combination of NMR techniques and
      molecular dynamic simulations. This protein inactivates streptomycin by
      transferring an adenyl group to position six of the streptidine moiety. Our
      combined approach provides valuable information about the bioactive conformation
      for both the antibiotic and ATP and shows that the molecular recognition process
      for streptomycin involves a conformational selection phenomenon. The binding
      epitope for both ligands has also been analysed by 1D-STD experiments. Finally,
      the specificity of the recognition process with respect to the aminoglycoside and
      to the nucleotide has been studied.

PMID- 15984038
TI  - [CH3--MoF], [CH2=MoHF], and [CH[triple bond]MoH2F] formed by reaction of laser
      ablated molybdenum atoms with methyl fluoride: persistent photoreversible
      interconversion through alpha-hydrogen migration and agostic interaction.
AB  - Simple molybdenum methyl, carbene, and carbyne complexes, [CH3--MoF], [CH2=MoHF],
      and [CH[triple chemical bond]MoH(2)F], were formed by the reaction of laser
      ablated molybdenum atoms with methyl fluoride and isolated in an argon matrix.
      These molecules provide a persistent photoreversible system through alpha
      hydrogen migration between the carbon and metal atoms: The methyl and carbene
      complexes are produced by applying UV irradiation (240-380 nm) while the carbyne
      complex is depleted, and the process reverses on irradiation with visible light
      (lambda>420 nm). An absorption at 589.3 cm(-1) is attributed to the Mo--F
      stretching mode of [CH3--MoF], which is in fact the most stable of the plausible
      products. Density functional theory calculations show that one of the alpha
      hydrogen atoms of the carbene complex is considerably bent toward the metal atom
      (angle-spherical HCMo=84.5 degrees ), which provides evidence of a strong agostic
      interaction in the triplet ground state. The calculated C[triple chemical bond]Mo
      bond length in the carbyne is in the range of triple-bond values in methylidyne
      complexes.

PMID- 15984039
TI  - A timely reassessment of early prediction in the bioavailability of orally
      administered drugs.

PMID- 15984040
TI  - Benzene formation at 70 degrees C by coupling of propylene on supported Pd
      nanoclusters.

PMID- 15984041
TI  - Synthesis of seven-membered-ring ketones by arylative ring expansion of alkyne
      substituted cyclobutanones.

PMID- 15984042
TI  - A proteome approach defines protective functions of tobacco leaf trichomes.
AB  - The leaf surface of most terrestrial plants is covered with plant hairs called
      trichomes. These epidermal appendages are thought to contribute to many aspects
      of plant defense against biotic and abiotic stresses in a variety of species.
      Trichome development has been intensively studied in Arabidopsis, and the
      phytochemical composition of trichomes was analyzed in a number of plant species.
      However, comparatively little is known of the proteins expressed. We therefore
      initiated a proteome approach to better define the cellular mechanisms operating
      in plant trichomes using two-dimensional gel electrophoresis to separate proteins
      of whole leaves and isolated trichomes. Tobacco was chosen due to the presence of
      glandular trichomes involved in the secretion of defense compounds. Comparative
      image analysis of the protein patterns indicated a number of spots, which were
      highly enriched in trichomes relative to leaves. These spots were excised for
      identification by mass spectrometry. The results showed that among the proteins
      specifically enriched in trichomes, the components of stress defense responses
      were strongly represented. The high expression of stress-related proteins was
      verified by Western blotting. Superoxide dismutase isoforms were additionally
      analyzed by activity staining. Our results demonstrate feasibility of the
      proteome approach to elucidate the cell biology of plant trichomes.

PMID- 15984043
TI  - Proteomic analysis of synaptosomes using isotope-coded affinity tags and mass
      spectrometry.
AB  - Synaptosomes are isolated synapses produced by subcellular fractionation of brain
      tissue. They contain the complete presynaptic terminal, including mitochondria
      and synaptic vesicles, and portions of the postsynaptic side, including the
      postsynaptic membrane and the postsynaptic density (PSyD). A proteomic
      characterisation of synaptosomes isolated from mouse brain was performed
      employing the isotope-coded affinity tag (ICAT) method and tandem mass
      spectrometry (MS/MS). After isotopic labelling and tryptic digestion, peptides
      were fractionated by cation exchange chromatography and cysteine-containing
      peptides were isolated by affinity chromatography. The peptides were identified
      by microcapillary liquid chromatography-electrospray ionisation MS/MS (muLC-ESI
      MS/MS). In two experiments, peptides representing a total of 1131 database
      entries were identified. They are involved in different presynaptic and
      postsynaptic functions, including synaptic vesicle exocytosis for
      neurotransmitter release, vesicle endocytosis for synaptic vesicle recycling, as
      well as postsynaptic receptors and proteins constituting the PSyD. Moreover, a
      large number of soluble and membrane-bound molecules serving functions in
      synaptic signal transduction and metabolism were detected. The results provide an
      inventory of the synaptic proteome and confirm the suitability of the ICAT method
      for the assessment of synaptic structure, function and plasticity.

PMID- 15984044
TI  - Proteomics of the rat gut: analysis of the myenteric plexus-longitudinal muscle
      preparation.
AB  - The enteric nervous system (ENS)--present all along the gastrointestinal tract -
      is the largest and most complicated division of the peripheral nervous system
      that can function independently of the brain. The peripheral nerve cells are
      organized in two separate but interconnected meshworks, called the myenteric and
      submucous plexus. The nervous control of intestinal motility is primarily
      governed by the myenteric plexus (MP), which lies in-between the longitudinal-
      (LM) and circular-muscle layers and regulates their functions. To determine
      whether the proteomic technology is adapted to the analysis of specific gut
      tissues, we dissected the MP-LM layers from the jejunum, ileum, and colon of Long
      Evans rats, homogenized them, and separated the proteins using two-dimensional
      gel electrophoresis. A subset of all the visualized protein spots, covering the
      entire range of molecular weights and isoelectric points, was then selected and
      further analyzed by matrix-assisted laser desorption/ionization-time of flight
      and liquid chromatography mass spectrometry. We identified around 80 proteins in
      each gut segment, and among those, five were segment-specific. Most of the
      proteins identified were derived from muscle cells, but we also detected some
      neuron-specific proteins. This study represents, to our knowledge, the first
      extensive protein catalog of a neuromuscular layer of the rat intestine and it
      may constitute the basis to understand pathophysiological mechanisms related to
      the ENS.

PMID- 15984045
TI  - Two-dimensional fluorescence difference gel electrophoresis analysis of the urine
      proteome in human diabetic nephropathy.
AB  - Urinary proteins may provide clues regarding pathogenesis of kidney disease as
      well as providing markers of disease activity. We employed two-dimensional
      differential in-gel electrophoretic analysis (2-D DIGE) to assess multiple urine
      samples in patients with diabetic nephropathy. Patient samples were collected as
      timed overnight collections. All the patients had longstanding diabetes, impaired
      renal function, and overt proteinuria. Control and patient urinary protein were
      analyzed by 2-D DIGE and DeCyder analysis. Ninety-nine spots were significantly
      regulated in the urine proteome of the diabetic samples, with 63 up- and 36 down
      regulated. One spot corresponding to a pI 5-6 and a molecular weight between 45
      and 66 kDa was consistently up-regulated by 19-fold across individuals in the
      diabetic group. Surface-enhanced laser desorption/ionization-time of flight
      analysis of in-gel tryptic digest of this spot identified this protein as alpha 1
      antitrypsin (AAT). ELISA of urine samples from a separate group of patients and
      controls confirmed a marked increase of AAT in diabetic patients. Immunostaining
      of human diabetic kidneys revealed up-regulation of AAT in areas of renal
      fibrosis. In conclusion, we developed a method to analyze numerous urine samples
      from patients and allowed for detection and identification of regulated urine
      protein spots.

PMID- 15984049
TI  - Comparative EST analyses in plant systems.
AB  - Expressed sequence tag (EST) data are a major contributor to the known plant
      sequence space. Organization of the data into non-redundant clusters representing
      tentative unique genes provides snapshots of the gene repertoires of a species.
      This chapter reviews availability of sequences and sequence analysis results and
      describes several resources and tools that should facilitate broad-based
      utilization of EST data for gene structure annotation, gene discovery, and
      comparative genomics.

PMID- 15984050
TI  - Quality of arthritis information on the Internet.
AB  - PURPOSE: The quality and reliability of Internet-based arthritis information were
      studied. METHODS: The search terms "arthritis," "osteoarthritis," and 'rheumatoid
      arthritis" were entered into the AOL, MSN, Yahoo, Google, and Lycos search
      engines. The Web sites for the first 40 matches generated by each search engine
      were grouped by URL suffix and evaluated on the basis of four categories of
      criteria: disease and medication information content, Web-site navigability,
      required literacy level, and currentness of information. Ratings were assigned by
      using an assessment tool derived from published literature (maximum score of 15
      points). RESULTS: Of the 600 arthritis Web sites identified, only 69 were unique
      and included in the analysis. Fifty-seven percent were .com sites, 20% .org
      sites, 7% .gov sites, 6% .edu sites, and 10% other sites. Total scores for
      individual sites reviewed ranged from 3 to 14. Eighty percent of .gov sites, 75%
      of .edu sites, 29% of other sites, 36% of .com sites, and 21% of .org sites were
      within the top tertile of scores. No Web site met the criterion for being
      understandable to people with no more than a sixth-grade reading ability. .Gov
      sites scored significantly higher overall than .com sites, .org sites, and other
      sites. .Edu sites also scored relatively well. CONCLUSION: The quality of
      arthritis information on the Internet varied widely. Sites with URLs having
      suffixes of .gov and .edu were ranked higher than other types of sites.

PMID- 15984052
TI  - Bibliography. Current world literature. Inflammatory diseases and infection.

PMID- 15984051
TI  - Bibliography. Current world literature. Headache.

PMID- 15984053
TI  - Patients more selective in choosing providers as benefits are scaled back.

PMID- 15984054
TI  - Structure-activity relationships of novel endomorphin-2 analogues with N-O turns
      induced by alpha-aminoxy acids.
AB  - Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2, EM-2) is a putative endogenous mu-opioid
      receptor ligand. To study the structure-activity relationship against its
      receptor, we introduced N-O turns into EM-2 and got the analogues with potent
      affinities for mu-opioid receptor. Our results indicated that N-O turn structures
      at the Pro2-aminoxy-Phe3 position of EM-2 analogues played important roles for
      their affinities. These novel analogues with N-O turns provided a new approach to
      develop potent analgesics related to EM-2.

PMID- 15984055
TI  - Rational design of composition and activity correlations for pH-responsive and
      glutathione-reactive polymer therapeutics.
AB  - Limited cytoplasmic delivery of enzyme-susceptible drugs remains a significant
      challenge facing the development of protein and nucleic acid therapies that act
      in intracellular compartments. "Smart" pH-responsive, membrane-destabilizing
      polymers present a new approach to shuttling therapeutic molecules past the
      endosomal membrane and into the cytoplasm of targeted cells. This report
      describes the use of a functionalized monomer, pyridyl disulfide acrylate (PDSA),
      to develop pH-responsive, membrane-destabilizing, and glutathione-reactive
      polymers by copolymerization with several pH-responsive and hydrophobic monomers.
      The activity of the carriers is described as a function of (a) increasing the
      length of the hydrophobic alkyl group substituted onto the pH-responsive monomer
      and (b) the incorporation of a hydrophobic monomer such as butyl acrylate (BA) on
      the pH sensitivity and membrane-destabilizing activity of new polymer
      compositions. The membrane-destabilizing activity of different polymer
      compositions was evaluated as a function of pH and polymer concentration using
      the red blood cell (RBC) hemolysis assay. Hemolysis results show that the
      increase in the hydrophobic character of the polymer backbone results in a shift
      in the pH sensitivities and an increase in the membrane-destabilizing activity.
      Results show that the observed hemolytic activities and pH sensitivity profiles
      could be designed across a range that matches the properties needed for enhancing
      the cytoplasmic delivery of macromolecular therapeutic.

PMID- 15984057
TI  - Interrogators cite doctors' aid at Guantanamo.

PMID- 15984056
TI  - A choice for the heart: it's easier to get data on a car than on a medical
      device.

PMID- 15984058
TI  - American College of Toxicology: policy statement on the use of animals in
      toxicology.

PMID- 15984059
TI  - Lifetime achievement award, Mildred S. Christian.

PMID- 15984060
TI  - Brazil's Samuel Dam: lessons for hydroelectric development policy and the
      environment in Amazonia.
AB  - Brazil's Samuel Dam, which formed a 540-km2 reservoir in the state of Rondonia in
      1988, provides lessons for development decisions throughout Amazonia and in other
      tropical areas. The decision to build the dam was heavily influenced by its role
      in the political strategies of key decision makers. Samuel illustrates both
      impacts and benefits of electricity supply and the dilemmas facing decision
      makers regarding the various options for planned electricity generation.
      Environmental costs included flooding forest and stimulating illegal logging
      activity throughout western Amazonia because of an exception opened for Samuel in
      Brazil's prohibition of export of raw logs. Samuel emitted substantially more
      greenhouse gases than would have been emitted by generating the same amount of
      electricity from oil. Contamination of fish in the reservoir resulted from
      methylation of mercury present in the soil. Social costs of the dam included
      resettlement of 238 families of farmers; impacts on indigenous people were
      indirect. Mitigating measures included faunal rescue and creation of a forest
      reserve. The lessons of Samuel include the need to consider a full range of
      alternatives prior to making decisions in practice and the importance of adhering
      to the logical sequence of decision making, where information is gathered and
      compared prior to the decision. It also shows the need to maintain flexibility
      when the costs and benefits of different alternatives change significantly over
      the course of the project's planning and execution, as occurred at Samuel.

PMID- 15984061
TI  - A framework for designing ecological monitoring programs for protected areas: a
      case study of the Galachos del Ebro Nature Reserve (Spain).
AB  - The assessment of management effectiveness in protected areas, i.e., the
      evaluation of whether management strategies are actually helping to achieve
      stated goals, is becoming a priority. In any such evaluation, accurate
      information concerning the dynamics of the managed system is required-information
      that is gathered through monitoring. Few protected areas, however, have well
      developed monitoring plans, and reserve managers are faced with a shortage of
      protocols for their design. This paper proposes a methodology, applicable to a
      wide range of situations, for designing such plans. The process begins with the
      precise definition of the aims of the monitoring plan, followed by the
      identification of key ecological processes and management objectives for the
      area, and finally the selection of a reduced set of indicators. These indicators
      are represented at three levels of growing complexity, allowing the plan to be
      followed in a modular fashion and in agreement with available resources.

PMID- 15984062
TI  - Evaluation of optically acquired zooplankton size-spectrum data as a potential
      tool for assessment of condition in the Great Lakes.
AB  - An optical plankton counter (OPC) potentially provides an assessment tool for
      zooplankton condition in ecosystems that is rapid, economical, and spatially
      extensive. We collected zooplankton data with an OPC in 20 near-shore regions of
      4 of the Laurentian Great Lakes. The zooplankton size information was used to
      compute mean size, biomass density, and size-spectra parameters for each
      location. The resulting metrics were analyzed for their ability to discriminate
      among the Great Lakes. Biomass density provided discrimination among lakes, as
      did several parameters describing spectra shape and distribution. A proposed
      zooplankton indicator, mean size (determined with OPC measurements in this
      study), was found to provide discrimination among lakes. Size-spectra-related
      parameters added increased ability to discriminate in conjunction with the
      biomass density (or mean size) metric. A discriminant function analysis of the
      multiple metrics (mean size, biomass density, and distribution parameters)
      suggests that a multi metric size-based approach might be used to classify
      communities among lakes improving a mean-size metric. The feasibility OPCs and
      size-based metrics for zooplankton assessment was found to have potential for
      further development as assessment tools for the biological condition of
      zooplankton communities in the Great Lakes.

PMID- 15984064
TI  - A daily time series analysis of stream water phosphorus concentrations along an
      urban to forest gradient.
AB  - During a 1-year period, we sampled stream water total phosphorus (TP)
      concentrations daily and soluble reactive phosphorus (SRP) concentrations weekly
      in four Seattle area streams spanning a gradient of forested to urban-dominated
      land cover. The objective of this study was to develop time series models
      describing stream water phosphorus concentration dependence on seasonal variation
      in stream base flows, short-term flow fluctuations, antecedent flow conditions,
      and rainfall. Stream water SRP concentrations varied on average by +/- 18% or +/-
      5.7 microg/L from one week to another, whereas TP varied +/- 48% or +/- 32.5
      microg/L from one week to another. On average, SRP constituted about 47% of TP.
      Stream water SRP concentrations followed a simple sine-wave annual cycle with
      high concentrations during the low-flow summer period and low concentrations
      during the high-flow winter period in three of the four study sites. These trends
      are probably due to seasonal variation in the relative contributions of
      groundwater and subsurface flows to stream flow. In forested Issaquah Creek, SRP
      concentrations were relatively constant throughout the year except during the
      fall, when a major salmon spawning run occurred in the stream and SRP
      concentrations increased markedly. Stream water SRP concentrations were
      statistically unrelated to short-term flow fluctuations, antecedent flow
      conditions, or rainfall in each of the study streams. Stream water TP
      concentrations are highly variable and strongly influenced by short-term flow
      fluctuations. Each of the processes assessed had statistically significant
      correlations with TP concentrations, with seasonal base flow being the strongest,
      followed by antecedent flow conditions, short-term flow fluctuations, and
      rainfall. Times series models for each individual stream were able to predict
      approximately 70% of the variability in the SRP annual cycle in three of the four
      streams (r2 = 0.57-0.81), whereas individual TP models explained approximately
      50% of the annual cycle in all streams (r2 = 0.39-0.59). Overall, time series
      models for SRP and TP dynamics explained 82% and 76% of the variability for these
      variables, respectively. Our results indicate that SRP, the most biologically
      available and therefore most important phosphorus fraction, has simpler and
      easier-to-predict seasonal and weekly dynamics.

PMID- 15984063
TI  - Effects of changing environments of mangrove creeks on fish communities at Trat
      Bay, Thailand.
AB  - Effects of changing environments of riverside mangroves, coastal land uses, and
      water quality on fish communities were studied in Bangphra and Thaprik creeks,
      Trat Bay, Thailand. Regression analysis revealed that fish species richness in
      the wet season had a negative relationship with water transparency, nitrate, and
      phosphate and a positive relationship with zooplankton. In the dry season,
      species richness had a negative relationship with nitrate and phosphate and a
      positive relationship with salinity, pH, and zooplankton. Abundances and species
      richness of fish declined over distance from downstream to upstream in both
      creeks. Riparian mangroves and water quality also declined with distance upstream
      in both creeks. Results from one-way analysis of variance and Tukey's HSD test
      revealed that the highest zooplankton volume with the lowest amounts of nitrate
      and phosphate were observed at the downstream station in both creeks in each
      season. Low zooplankton volume with high amounts of nitrate and phosphate were
      found at the midstream and upstream stations of the creeks. The midstream and
      upstream stations of Bangphra Creek had low to moderate abundance of mangroves
      along the riversides, whereas shrimp farms were mainly found along the riversides
      at the midstream and upstream stations of Thaprik Creek. Correlation analysis
      results of land-use types and the significant habitat factors were discussed.
      This study found that mangrove degradation, shrimp farming, and residential and
      agricultural areas altered water quality and the health of fish habitats, causing
      the decreases in fish abundance and species richness.

PMID- 15984065
TI  - Georelational analysis of soil type, soil salt content, landform, and land use in
      the Yellow River Delta, China.
AB  - The Yellow River Delta, one of China's three major river deltas, is becoming a
      major region for the development of agriculture and fisheries. Protecting the
      delicate ecology of newly formed aquatic systems as well as the evolution of
      soils, natural vegetation, and fauna on older upland environments in the delta is
      a priority in planning for the wise use of the delta's resources for future
      agricultural development. In this article, we use a Geographic Information System
      (GIS) to analyze relationships between land-use/ land-cover characteristics in
      the Dongying municipality, one of the most intensely developed areas of the
      delta, and spatial variations in soil salinity and landforms. This analysis
      reveals that soil salt content decreases from regionally high values in isolated
      depressions to relatively moderate values in embanked former back swamps, with
      the lowest values occurring in abandoned river courses. Comparing the present
      land use on this soil salinity-landform pattern shows that it is basically at
      odds with general concepts of land suitability for agricultural utilization of
      saline soils. Crop-based agriculture in the region is probably overdeveloped,
      whereas more appropriate agricultural development, like cattle and forest
      production, is underrepresented. Future development should focus on converting
      farmland in embanked former back swamps and abandoned river courses into
      grasslands and forests. Crop-based agriculture (up to 151,000 ha) could be
      planned at the low-salinity terrace uplands and flood plains. The article
      provides guidelines for decision-makers regarding agricultural land use and
      wetland protection in the Yellow River Delta.

PMID- 15984066
TI  - Modeling long-term risk to environmental and human systems at the Hanford Nuclear
      Reservation: scope and findings from the initial model.
AB  - The Groundwater Protection Project at the US Department of Energy Hanford Site in
      Washington State is currently developing the means to assess the cumulative
      impact to human and ecological health and the regional economy and cultures from
      radioactive and chemical waste that will remain at the Hanford Site after the
      site closes. This integrated system is known as the System Assessment Capability
      (SAC). The SAC Risk/Impact Module discussed in the article uses media- and time
      specific concentrations of contaminants estimated by the transport models of the
      integrated system to project potential impacts on the ecology of the Columbia
      River corridor, the health of persons who might live in or use the corridor or
      the upland Hanford environment, the local economy, and cultural resources.
      Preliminary Monte Carlo realizations from the SAC modeling system demonstrate the
      feasibility of large-scale uncertainty analysis of the complex relationships in
      the environmental transport of contaminants on the one hand and ecological,
      human, cultural, and economic risk on the other. Initial impact results show very
      small long-term risks for the 10 radionuclides and chemicals evaluated. The
      analysis also helps determine science priorities to reduce uncertainty and
      suggests what actions matter to reduce risks.

PMID- 15984067
TI  - Applicability of a septic tank/engineered wetland coupled system in the treatment
      and recycling of wastewater from a small community.
AB  - A septic tank (ST)/engineered wetland coupled system used to treat and recycle
      wastewater from a small community in Dar es Salaam, Tanzania was monitored to
      assess its performance. The engineered wetland system (EWS) had two parallel
      units each with two serial beds packed with different sizes of media and
      vegetated differently. The larger-sized medium bed was upstream and was planted
      with Phragmites (reeds) and the smaller-sized medium bed was downstream and was
      planted with Typha (cattails). The ST/EWS coupled system was able to remove
      ammonia by an average of 60%, nitrate by 71%, sulfate by 55%, chemical oxygen
      demand by 91%, and fecal coliform as well as total coliform by almost 100%. The
      effluent from the ST/EWS coupled system is used for irrigation. Notably, users of
      the recycled irrigation water do not harbor any negative feelings about it. This
      study demonstrates that it is possible to treat and recycle domestic wastewater
      using ST/ EWS coupled systems. The study also brings attention to the fact that
      an ST/EWS coupled system has operation and maintenance (O&M) needs that must be
      fulfilled for its effectiveness and acceptability. These include removal of
      unwanted weeds, harvesting of wetland plants when the EWS becomes unappealingly
      bushy, and routine repair.

PMID- 15984068
TI  - Learning machines applied to potential forest distribution.
AB  - The clearing of forests to obtain land for pasture and agriculture and the
      replacement of autochthonous species by other faster-growing varieties of trees
      for timber have both led to the loss of vast areas of forest worldwide. At
      present, many developed countries are attempting to reverse these effects,
      establishing policies for the restoration of older woodland systems.
      Reforestation is a complex matter, planned and carried out by experts who need
      objective information regarding the type of forest that can be sustained in each
      area. This information is obtained by drawing up feasibility models constructed
      using statistical methods that make use of the information provided by
      morphological and environmental variables (height, gradient, rainfall, etc.) that
      partially condition the presence or absence of a specific kind of forestation in
      an area. The aim of this work is to construct a set of feasibility models for
      woodland located in the basin of the River Liebana (NW Spain), to serve as a
      support tool for the experts entrusted with carrying out the reforestation
      project. The techniques used are multilayer perceptron neural networks and
      support vector machines. Their results will be compared to the results obtained
      by traditional techniques (such as discriminant analysis and logistic regression)
      by measuring the degree of fit between each model and the existing distribution
      of woodlands. The interpretation and problems of the feasibility models are
      commented on in the Discussion section.

PMID- 15984069
TI  - PA: Visiting CNA no longer able to climb/walk: attachment to labor force dictates
      benefits award.

PMID- 15984070
TI  - What are the real risks of antidepressants?

PMID- 15984071
TI  - The homeless mentally ill.

PMID- 15984072
TI  - Stress takes the edge off.

PMID- 15984073
TI  - Questions and answers. What is the amygdala, and what are its functions?

PMID- 15984074
TI  - Emphysema. First, stop smoking.

PMID- 15984075
TI  - Health tips. Upper body exercises.

PMID- 15984076
TI  - Study find bone benefits from heart medications.

PMID- 15984077
TI  - Phobias. Overcoming your fears.

PMID- 15984078
TI  - Vitamin D. Individualize your dose.

PMID- 15984079
TI  - My doctor said to be careful not to take too much acetaminophen while I'm taking
      an acetaminophen combination prescription pain reliever. What kinds of products
      contain acetaminophen?

PMID- 15984080
TI  - The type III cytotoxins of Yersinia and Pseudomonas aeruginosa that modulate the
      actin cytoskeleton.
AB  - Initial studies of how bacterial toxins modulate the actin cytoskeleton have
      focused primarily on the mode of action of these toxins. More recently, studies
      have addressed the molecular interactions of these toxins with host cell
      signaling pathways and how toxins modulate cellular physiology. Although each
      individual toxin has a unique mode of action, general themes have started to
      emerge between bacterial pathogens. During the course of an infection, many
      pathogenic bacteria produce toxins that target the actin cytoskeleton and its
      regulatory proteins. Toxins can either act as positive regulators promoting the
      assembly of filamentous actin structures or, alternatively, as negative
      regulators promoting actin filament disassembly. Modulation of the actin
      cytoskeleton facilitates various infectious processes critical for the success of
      the pathogen. Intracellular bacteria such as Salmonella typhimurium utilize
      toxins to promote both assembly and disassembly of the actin cytoskeleton during
      the infection process. Temporal regulation of toxin activities results in
      internalization of the bacterium by epithelial cells into specialized vacuoles
      permissive for growth. In contrast, Yersinia utilizes actin modulating toxins to
      block internalization by professional antigen-presenting cells such as
      macrophages and dendritic cells. Modulation of the immune response through the
      production of actin-regulating toxins appears to be a common approach adopted by
      several extracellular pathogens. Thus the repertoire of actin-modifying toxins
      produced by various species is specifically tailored to facilitate the lifestyle
      of the pathogen. The presence of multiple toxins that modulate the activation
      state of actin shows the importance of interfering with the cytoskeleton to
      neutralize the host's innate immune system for the survival and growth of
      Yersinia and P. aeruginosa.

PMID- 15984081
TI  - [Use of ruthenuim 106 in retinoblastoma treatment].
AB  - The Charles University Teaching Hospital in Prague - Motol started to treat
      patients with retinoblastoma by means of brachytherapy after obtaining the
      permission to use closed source of ionizing radiation in the beginning of the
      year 2003. The applicator containing ruthenium (106Ru) emitting mostly the beta
      radiation was chosen. Half-life is 369 days and the nominal activity of the
      source is 21.1 MBq. The applicator is placed in place for one to several days
      according to the prominence of the tumor and actual activity of the source.
      Duration of the application is calculated with a special program. In the year
      2003, three patients with retinoblastoma were treated. In one case bilateral
      involvement was determined, and the brachytherapy was used for treatment of both
      eyes. The next patient was treated twice; one treatment followed the other with
      different localization of the applicator because of too large basis of the tumor.
      In 2003, altogether the brachytherapy was used for treatment of retinoblastoma
      five times. In all cases, the combined treatment (chemoreduction, teletherapy,
      transpupillary thermotherapy, or cryotherapy) was performed. One eyeball was
      enucleated because of severe post-radiation retinopathy, the second one for
      persisting tractional retinal detachment. In remaining cases no serious
      complications or progression of the malignancy were observed.

PMID- 15984082
TI  - Preadolescent clues to understanding depression in girls.
AB  - Between the ages of 10 and 15, increases in depression among girls result in a
      rate that is twice as high as the rate of depression in boys. This sex difference
      remains throughout early and middle adulthood. Prior to early adolescence, there
      is essentially no sex difference in the rate of depression. The aim of the
      present review is to examine whether the preadolescent period is a time during
      which precursors to depression in girls can be identified. First, existing areas
      of research on explaining sex differences in depression, including cognitive and
      affiliative style and the socialization of emotion, are reviewed. Second, the
      hypothesis that for some girls, preadolescent precursors to depression take the
      form of excessive empathy, compliance and regulation of negative emotions is
      articulated. Third, ways of building on existing models by including the proposed
      preadolescent precursors are proposed. Finally, approaches to testing the
      hypotheses that individual differences in these domains during preadolescence may
      explain later individual differences in adolescent onset depression are explored.

PMID- 15984083
TI  - Anxiety disorders in childhood: casting a nomological net.
AB  - Empirical research highlights the need for improving the childhood anxiety
      disorder diagnostic classification system. In particular, inconsistencies in the
      stability estimates of childhood anxiety disorders and high rates of comorbidity
      call into the question the utility of the current DSM criteria. This paper makes
      a case for utilizing a nomological net model for advancing the understanding of
      childhood anxiety disorders. In this article, we discuss measurement and
      assessment issues related to improving the childhood anxiety disorder diagnostic
      system and show how these issues can be addressed by employing the nomological
      net of childhood anxiety. Because employing the nomological net involves drawing
      from etiological process theories to facilitate classification and assessment, an
      integrative model of childhood anxiety disorders is presented as a tentative
      heuristic. Then evidence for the existing symptom sets is discussed in the
      context of how process theory mechanisms may be utilized to improve
      classification and assessment. Testable hypotheses are presented. Measurement,
      disorder definition, treatment, and policy implications are also discussed.

PMID- 15984085
TI  - Intergenerational transmission of role reversal between parent and child: dyadic
      and family systems internal working models.
AB  - The current study examined the intergenerational transmission of role reversal
      within a developmental psychopathology framework. Role reversal is a relationship
      disturbance in which a parent looks to a child to meet the parent's need for
      comfort, parenting, intimacy, or play, and the child attempts to meet these
      needs. In a normative sample, n=138, fathers and mothers reported on childhood
      role reversal with their mothers as part of the Adult Attachment Interview, AAI
      (George, Kaplan, & Main, 1984). Mother-child role reversal was then assessed in
      an observational paradigm when children were 2 years of age. Based on theories of
      dyadic and family systems internal working models we hypothesized gender specific
      replications of role reversal in the next generation. Indeed, mothers who
      reported role reversal with their mothers during the AAI tended to engage in
      higher levels of role reversal with their toddler-aged daughters. Furthermore,
      when fathers reported role reversal with their mothers during the AAI, mothers
      tended to engage in higher levels of role reversal with their toddler-aged sons.
      The importance of the inclusion of fathers in family research, the relationship
      between role reversal and attachment, and implications for preventive
      interventions are discussed.

PMID- 15984084
TI  - Parent management of attendance and adherence in child and adolescent therapy: a
      conceptual and empirical review.
AB  - There have been impressive, recent advances in the development of efficacious
      treatments for child and adolescent behavior problems. However, specific methods
      for delivering these treatments in a way that amplifies their efficacy have not
      been well articulated. Although many factors may be involved, attendance and
      adherence to treatment are arguably the most basic necessities for effective
      treatment delivery. We provide a conceptual and empirical review of past research
      on attendance and adherence to child and adolescent therapy, with a special focus
      on the importance of parents/guardians in managing treatment participation. Our
      review demonstrates that attendance and adherence are associated with a range of
      significant methodological, clinical, and financial outcomes. Several
      pretreatment predictors of attendance and adherence have been identified;
      however, to date only 12 controlled, clinical trials have evaluated strategies
      for enhancing attendance and adherence to child therapy. We conclude with an
      agenda for advancing research on the prediction and enhancement of attendance and
      adherence to child therapy as a means of improving the efficiency and
      effectiveness of child treatments.

PMID- 15984086
TI  - Development and preliminary validation of the caregiving behavior system:
      association with child attachment classification in the preschool strange
      situation.
AB  - The Marvin and Britner system for classifying caregiver behavior patterns in the
      preschool Strange Situation is presented to complement the Cassidy and Marvin
      (1992) preschool child-parent attachment classification system. Participants were
      110 mothers and their preschool children (aged 2 to 4 years) with medical risks
      (epilepsy or mild cerebral palsy) or no diagnosis (i.e., healthy). As coded by
      reliable, independent raters, there was a highly significant level of concordance
      between the 5-category caregiver and child classifications in the preschool
      Strange Situation across the medical risk levels. In comparison to other
      caregivers, mothers classified as secure in their caregiving behavior pattern
      were rated as more sensitive; they also showed greater delight and were more
      supportive of their children's exploration. Combinations of the ten, 9-point
      caregiver rating scales were useful in discriminating among the insecure
      caregiver patterns.

PMID- 15984087
TI  - Comparison of sucking patterns at introduction of oral feeding and at term in
      Israeli and American preterm infants.
AB  - BACKGROUND: It has been hypothesized that early initiation of oral feeding in
      premature infants may enhance the maturation of sucking patterns. AIM: To compare
      preterm infant sucking characteristics in urban level III neonatal care units in
      the USA and Israel. The two hospitals have different practices regarding the
      introduction of oral feeding. METHODS: Infants were assessed at 34-35 wk
      postconceptional age (PCA) and at term. Sucking parameters were assessed with the
      Kron's Nutritive Sucking Apparatus. RESULTS: 70 infants (38 Americans and 32
      Israelis) participated in the study. Oral feedings were initiated earlier (32.6
      +/- 4.3 vs 34.5 +/- 1.8 wk PCA, p < 0.01) and full oral feedings were reached
      earlier (35.4 +/- 2.8 vs 36.5 +/- 2.5 wk PCA, p < 0.05) in the USA infants.
      American preterm infants produced significantly more sucks (p < 0.001), had a
      higher suck rate (p < 0.001), more sucks per burst (p < 0.05), and a shorter
      interburst width (p < 0.01) at 34 wk PCA than Israeli infants. At term, American
      infants produced significant more sucks (p < 0.001), higher suck rate (p <
      0.001), shorter intersuck width (p < 0.001), and a shorter interburst width (p <
      0.05) than the Israeli infants of the same PCA. CONCLUSION: Different practices
      in the care of preterm infants, such as postconceptional age at introduction of
      oral feeding, may play a role in the development of feeding and feeding
      organization at term.

PMID- 15984088
TI  - Annual review of cytokines in cancer management. Summaries of selected studies of
      darbepoetin alfa, pegfilgrastim, palifermin, and other cytokines presented at six
      major meetings held in 2004.

PMID- 15984089
TI  - [Proceedings of the 97th Annual Congress of the Swiss Ophthalmological Society.
      Montreux, Switzerland, 15-18 September 2004].

PMID- 15984090
TI  - Presumptions of service connection for diseases associated with service involving
      detention or internment as a prisoner of war. Affirmation of interim final rule
      as final rule.
AB  - This document affirms as final, without change, an interim final rule that
      established presumptions of service connection for atherosclerotic heart disease,
      hypertensive vascular disease, and stroke in former prisoners of war; set forth
      guidelines to govern future actions by the Department of Veterans Affairs (VA) to
      establish presumptions of service connection for other diseases associated with
      service involving detention or internment as a prisoner of war; and revised VA's
      regulations to conform to statutory changes made by the Veterans Benefits Act of
      2003.

PMID- 15984091
TI  - Revisions to the Public Information Policy.

PMID- 15984092
TI  - Top standards compliance issues for 2004.

PMID- 15984093
TI  - Clarification on the Information Accuracy and Truthfulness Policy.

PMID- 15984094
TI  - Detrusor contractility: progress and new subjects since the second OBSLUT in
      1995. Proceedings of the 6th Oslo Biennial Symposium on Lower Urinary Tract
      Physiology and Pathophysiology.

PMID- 15984095
TI  - Corrections to Element of Performance.

PMID- 15984096
TI  - [Abstracts of the XXIX Annual Congress of the Mexican Society of Human Genetics].

PMID- 15984097
TI  - Managing hearing loss in children and adults: Singapore context.
AB  - Hearing loss is common in Singapore, with as many as 360,000 persons affected.
      With Singapore's ageing population, this prevalence is expected to increase.
      Modern hearing devices have the potential to restore hearing in most patients.
      Cochlear implants can restore hearing in those with even profound total hearing
      loss, by stimulating the auditory nerve directly without the need for viable
      cochlear hair cells. A holistic approach to managing deafness is necessary,
      including addressing psychosocial issues. Many of the problems experienced by the
      hearing-impaired are caused by the ignorance and lack of understanding from other
      people around him/her. "Reverse education therapy" refers to the effective
      education of these people, to directly benefit the hearing-impaired. In children,
      hearing restoration together with early detection and effective rehabilitation
      enable up to 80% to 90% of those born with significant hearing loss to cope well
      in mainstream education. The infrastructure to support them and facilitate their
      integration into mainstream society is necessary, and some of these are in place
      in Singapore. Leisure time noise-induced hearing loss in children is becoming
      increasingly important. In adults, societal support and understanding are just as
      important, particularly towards the elderly and pre-lingually deafened adults.
      Public education in Singapore is necessary, including that on the recognition of
      the abilities of successfully treated individuals, as well as that on showing
      more compassion, support and patience towards those who have not benefited
      sufficiently from treatment. In the future, there is potential for the clinical
      application of cochlear hair cell/auditory nerve preservation and regeneration.

PMID- 15984098
TI  - Designing a powerful 2DE experiment.

PMID- 15984099
TI  - Tears hold clues to eye disease.

PMID- 15984100
TI  - Katie Cottingham reports from the American Association for Cancer Research 96th
      Annual Meeting--Anaheim, Calif. Have biomarkers, will validate.

PMID- 15984102
TI  - GC-MS system has noise in the background that comes and goes, creating a baseline
      with a "chunky" appearance.

PMID- 15984101
TI  - Proteomics reveals effects effects of aquaculture on fish.

PMID- 15984103
TI  - [Treatment of serious allergic reactions].

PMID- 15984104
TI  - Bupropion: a German review.

PMID- 15984105
TI  - Management of insomnia: a place for traditional herbal remedies.
AB  - (1) Insomnia should be treated first with non drug measures; this has
      traditionally involved the use of herbal remedies. (2) About 20 plants are
      approved in France in the production of medications 'traditionally used' for
      minor sleep disturbances. Virtually nothing is known of their efficacy or
      potential dangers. (3) Most of these plants are suspected of toxicity and should
      therefore be avoided, especially in view of their unproven efficacy. (4)
      Littleleaf linden, vervain, melissa and orange flower have no demonstrated
      efficacy but are safe and can therefore be used. Similarly, there are no
      scientific grounds for rejecting preparations based on hawthorn or passiflora.
      (5) Available data suggest that valerian extracts have a modest impact on
      subjective sleep quality; they are nevertheless more effective than a placebo.
      Valerian products that do not contain valepotriates have no apparent adverse
      effects. It is best to avoid high-titre alcoholic extracts and powdered valerian
      root, and to select aqueous extracts and low-titre hydro-alcoholic preparations.

PMID- 15984107
TI  - Drug packaging quality: neglected by regulatory agencies.

PMID- 15984106
TI  - Adjuvant hormone therapy for breast cancer: alternatives to tamoxifen.
AB  - (1) After surgical excision of hormone-receptor-positive non metastatic breast
      cancer in postmenopausal women, a meta-analysis of 55 trials has shown that
      adjuvant tamoxifen, 20 mg/day for 5 years, reduces the risk of relapse by 8% and
      the risk of death by 5% (absolute values). The benefit of treatment beyond 5
      years remains to be established. (2) Preliminary four-year results from a double
      blind randomised controlled trial comparing anastrozole with tamoxifen (ATAC
      trial) indicated an advantage for anastrozole in reducing the risk of relapse.
      There was no difference in survival rate. Women taking anastrozole experienced
      more sexual dysfunction and an increased risk of osteoporotic fractures, whereas
      tamoxifen was associated with an increased risk of thrombosis and endometrial
      cancer. The trial's methodology is controversial, however, and conclusions
      concerning the relative risk-benefit balances of these two drugs must await the
      full 5-year results. (3) A double-blind placebo-controlled trial of letrozole,
      prescribed after 5 years of adjuvant tamoxifen, was stopped early after a median
      follow-up of 2.4 years. When extrapolated to 4 years, the results suggest that
      letrozole reduced the risk of relapse (7%, compared to 13% with tamoxifen) but
      had no effect on survival. (4) A double-blind trial comparing tamoxifen with
      exemestane in 4742 women who had already received tamoxifen for two to three
      years showed a higher three-year disease-free survival rate with exemestane
      (91.5% versus 86.8%). Overall survival did not differ between the two groups. (5)
      Pending results of further clinical trials, tamoxifen remains the first-line
      adjuvant hormone therapy for most postmenopausal women with hormone-receptor
      positive non metastatic breast cancer.

PMID- 15984109
TI  - Mother nature's DNA.

PMID- 15984108
TI  - How to avoid future Vioxx-type scandals.
AB  - The market withdrawal of rofecoxib (Vioxx) in September 2004 was the logical, if
      long-overdue, result of what has become a major scandal. How can similar
      situations be avoided in the future? The authorities must of course come to grips
      with their responsibilities, but caregivers, patients and journalists also have a
      role to play. This was the theme of the press conference held at Prescrire
      headquarters after the annual awards ceremony on 20 January 2005

PMID- 15984110
TI  - Virus filtration. Technical report No. 41.

PMID- 15984111
TI  - [Waterhouse-Friderichsen cases in the archives of ZMS PAM--epidemiological
      conditions and diagnostic difficulties].
AB  - 15 cases of meningococcal infections from 2003-2004 were discussed in the study.
      Their therapy ended in failure and they had been typically autopsied in our
      Forensic Med. Department. During the autopsy material for classical
      microbiological investigations was collected. That type of death is characterised
      with pathognomonic and autopsy image. The problem is the microbiological
      identification of the pathogen group and type. It is connected with the
      characteristic of the analysed material and the biological features of Neisseria
      meningitidis. The molecular and genetic methods show their usefulness in this
      type of diagnostic of the properly selected and collected material which
      typically are: cerebrospinal fluid, brain tissue with the arachnoid membranes and
      spleen tissue.

PMID- 15984112
TI  - [Artefacts in the anthropologic (craniologic) material at the archives of ZMS PAM
      -possible diagnostic difficulties].
AB  - In the study we presented some of the more interesting forms of artefacts which
      had been documented during last 7 years of the anthropological laboratory of the
      Forensic Med. Department of the Pomeranian Med. Univ. We also present the
      outgoing conclusions concerning the possible diagnostic difficulties. The
      descriptions of archaeological as well as autopsy-derived material were included.
      The anthropological analysis was made using data contained in the classic works
      of literature, which included cranioscopy. The longitudinal and transversal
      intersections of skulls were used for the analysis of their deformations.

PMID- 15984113
TI  - [Dating the time of death of an unknown individual on the basis of remnants of
      material culture--a case study].
AB  - The anthropological laboratory of the Forensic Medicine Department PAM carries
      out a lot of cases concerning identification on the basis of skeletal remains.
      Standard procedures are: anthropological analysis, estimation of time of burial
      of the remains, characteristics of morbid changes and the cause of death as well
      as skull based face reconstruction and super-projection. Very often some tiny
      details can be useful while answering questions relating to the origin of the
      remains, time of death, or identity of an unknown individual. In the described
      case, the key method was analysis of two pieces of clothing found inside the
      skull.

PMID- 15984114
TI  - [Application of anthropometric methods in comparative identification based on
      monitoring recordings].
AB  - In recent years more and more often cases have occurred concerning identification
      of suspects of various crimes for eg. car theft from parking lots in front of
      supermarkets or money from ATMS. It often happens that such places are monitored
      twenty-four hours a day. Still, both the quality of cameras and their location in
      the wrong places cause the recordings to be illegible. In the present pager, we
      present two cases of this type, where by applying computer graphics and
      anthropometric methods contributed to identification of law-breakers.

PMID- 15984116
TI  - [Problems with terminology in forensic science, medicine, and law].

PMID- 15984115
TI  - [A case of considerable incongruence between the expected and actual height of an
      individual, who was identified with methods of super-projection and comparative
      testing of DNA].
AB  - Anthropology is used, among others, in forensic medicine for identification of
      skeletal remains. The case we would like to introduce concerns the remains of an
      unknown man, which were subjected to identification tests in anthropological
      laboratory of the Forensic Medicine Department PAM. Anthropological analysis let
      us define the basic distinctive features, on the basis of which police selected
      an individual, whose features corresponded with the collected data. To confirm
      identity we used the super-projection method. We obtained the superposition of
      the estimation craniometric and cephalometric points which were suitable for,
      which was absolutely sufficient to regard the super-projection as successful.
      Comparing anthropometric features of the unknown man and appointed individual we
      noted considerable differences in height values. Comparative research of DNA,
      however, confirmed the individual's identity.

PMID- 15984118
TI  - [STR and RFLP polymorphism in paternity determination based on family
      investigation].
AB  - This paper shows a paternity examination of a deceased putative father carried
      out on the basis of his family investigation. Statistical evaluation proved the
      defendant's paternity using STR and RFLP analyses with the probability of more
      than 99,999% (PI > 100 000). The restriction analysis has proven considerably
      more informative than the amplification analysis, which means seven RFLP markers
      correspond with the similar paternity indices of the fifteen STR markers.

PMID- 15984117
TI  - [Polymorphism of X-STR loci DXS7108 and DXS1196 in the Northern Polish
      population].
AB  - This paper describes results of a population study of two X-linked STR
      microsatellite markers: DXS7108 and DXS1196. 298 samples of DNA of unrelated
      persons (male and female) from the Northern part of Poland were analyzed. DNA was
      isolated using a non-enzymatic method. After amplification PCR products were
      separated by means of capillary electrophoresis using the ABI PRISM 310 Genetic
      Analyzer. The most common alleles of each locus were sequenced and used as a
      control ladder to type unknown samples. Testing for Hardy-Weinberg equilibrium
      (HWE) showed no significant deviation for these two loci. Statistical parameters
      (PD, HET, MEC) showed that examined systems are useful in forensic medicine.

PMID- 15984119
TI  - [Changes of the concentration of lipid peroxidation products and thiol groups in
      rat brains with long-term intoxication with methanol].
AB  - The aim of this paper was to define the influence of long-term methanol
      intoxication on the changes of end products of lipid peroxidation, reacting with
      thiobarbituric acid (TBA-reactive products) and free SH-group concentration in
      rat brains. The experiment was conducted on male Lewis rats. The experimental
      groups received a 1-molar methanol solution and the control group received tap
      water. The animals were killed after 4, 8 and 12 weeks of intoxication and their
      brains were collected for further examination, which encompassed measurement of
      the concentration of TBA-reactive products and free SH-groups. The revealed
      changes of TBA-reactive products and free SH-group concentration were not
      statistically significant.

PMID- 15984120
TI  - [Carbon monoxide poisoning in the autopsy material of the Department of Forensic
      Medicine, Medical University of Bialystok in the years 1998-2003].
AB  - In years 1998-2003, carbon monoxide poisonings were a death cause in 121 cases
      (5.0%) of a total of 2408 autopsy reports reviewed. Possible relationships
      between carboxyhemoglobin concentration and ethanol concentration, age and gender
      of the victims were assessed. The place of intoxication was also considered.
      Seasonal distribution of CO intoxication was confirmed. Males accounted for more
      than 77% of all victims. The highest concentration of carboxyhemoglobin was found
      in the age group of 31-40 years. A protective effect of low ethanol concentration
      (< 3 per thousand) was noted in persons exposed to CO. The COHb level was
      measured by the Wolff's method.

PMID- 15984122
TI  - [Medicolegal autopsy--realization of procedural and essential requirements].
AB  - According to law a medicolegal autopsy can in practice be carried out by every
      physician. Strict cooperation between the physician and the prosecutor must
      guarantee the carrying out of all formal and medical procedures and in the
      meantime without overstepping the competence of the expert. The lack of precise
      regulations concerning all medicolegal procedures during the autopsy (like those
      from 1928) cause conflicting situations which in turn may not allow for all
      essential procedures to be undertaken in order to solve a specific case.

PMID- 15984121
TI  - [Toxicological analysis of selected 1,4-dihydropyridine calcium channel blockers
      in the diagnosis of intoxications].
AB  - This study is aimed at evaluating effective techniques of qualitative and
      quantitative analysis of selected 1,4-dihydropyridine calcium channel blockers,
      useful both for thanatological diagnosis of intoxications as well as monitoring
      therapy. The studies took advantage of gas chromatography (GLC) and high
      performance liquid chromatography (HPLC). Isolation of studied compounds from
      biological material was performed using classical and solid phase extraction
      procedures (SPE) such as Bond Elut LRC (Varian), Abselut Nexus (Varian), STRATA C
      - 18 E (Phenomenex). The program included analysis of nine of the most frequently
      prescribed derivatives: nifedipine, felodipine, amlodipine, nicardipine,
      nimodypine, nilvadipine, nitrendipine, nisoldipine, isradipine.

PMID- 15984123
TI  - [Legal basis for ontogenetic sex judgment in sex disapproval syndrome in the form
      of transsexualism. Comparison of the situation in Poland and in some other
      countries].
AB  - Sex disapproval syndrome in the form of transsexualism is characterized by
      incompatibility of biological and psychically-emotional sex. This incompatibility
      leads to a discrepancy between one's social role and his or her biological sex.
      The aim of this paper is to present and compare the legal basis for ontogenetic
      sex judgment in the sex disapproval syndrome in the form of transsexualism in
      Poland and in some other countries. Poland, contrary to some other countries,
      does not have any appropriate legislation for determining the above issue. So far
      all judgment has been based on exponential activities, in anticipation for the so
      called transsexual act. This act may be created on the basis of existing
      legislation in other European countries, which is briefly presented in the work.

PMID- 15984124
TI  - [Medico-legal opinion in establishing "exposure to direct danger of death or
      grave detriment to health"].
AB  - This paper deals with the problem of competence of the forensic expert opinions
      on the exposure to "direct danger of death or grave detriment to health".
      According to the analysis of judicial verdicts and the comments of lawyers
      "direct danger" depends closely on the probability, time and number of
      occurrences between the behavior of the perpetrator and the threatening act. The
      competence of the forensic expert does not allow for the legal qualification of
      the act but for the assessment of from the medicolegal point of view, defining
      the threat and possible outcomes in a descriptive fashion. The assessment of
      "direct danger" should be the result of close cooperation between the judicial
      representative and forensic expert.

PMID- 15984125
TI  - [Uncertainty of measurement as an integral part of the result and a tool of
      quality of work improvement for the chemical-toxicology laboratory].
AB  - An uncertainty in measurements is a numerical defined range that is supposed to
      find a true value with a given level of probability. The purpose of this study
      was to estimate a type A and B of uncertainty in the analysis of ethanol using
      the ADH method and prove it to be useful in lab practice. A large percentage of
      uncertainty was shown for pipetting of the ADH and perchloric acid solutions.
      This result formed the basis to make an effort in order to improve the procedure.
      The results of uncertainty of measurements given by method B are similar to the
      empiric method A results. The reduction of expenses and time saving of the
      analysis is an important advantage of the described way of uncertainty.

PMID- 15984126
TI  - [Pericardial tamponade caused by parenteral nutrition solution].
AB  - The authors present a case of a 4-year old girl, poisoned by an unknown
      substance. She died because of pericardial tamponade with parenteral nutrition
      solution.

PMID- 15984127
TI  - [A fatal accident due to harvester wheel explosion--a case report].
AB  - A fatal accident of a 48 year old woman due to harvester wheel explosion has been
      presented in this paper. A faulty technical condition of the wheel and the fact
      that it had been pumped to a pressure exceeding the permissible limit was the
      reason for the explosion. The woman sustained multiorgan injuries and microscopic
      examination revealed inter-alveolar septa rupture and intra-alveolar haemorrhage
      and oedema. The microscopic changes of the lungs prove that the shock wave was
      released during the wheel explosion.

PMID- 15984128
TI  - [Standards of DNA laboratories, criterium of Polish Society of Forensic Medicine
      and Criminology].

PMID- 15984130
TI  - Wanless: a public health knight. Securing good health for the whole population.

PMID- 15984129
TI  - [Chemical diagnosis of carbamazepine intoxication and its usefulness in
      toxicological jurisprudence].
AB  - Intoxication with carbamazepine (Amizepine, Tegretol) represents a significant
      problem of clinical and forensic toxicology which frequently develops
      independently of the commonly used monitored therapy. In the study a technique of
      qualitative and quantitative analysis applied to carbamazepine (CBZ) as well as
      its metabolites carbamazepine 10, 11-epoxide (CBZ-E) and 10, 11
      dihydroxycarbamazepine (CBZ-DH) in biological material using high-performance
      liquid chromatography (HPLC) was presented. The studies also involve isolation of
      studied compounds using solid phase extraction, SPE-Abselut NEXUS (Varian),
      establishment of calibration range and validation of analytical parameters. This
      was followed by a discussion of results obtained in routine diagnostic
      investigations in cases of intoxications, corroborating practical suitability of
      the designed technique.

PMID- 15984131
TI  - Priorities for research for oral health in the 21st century--the approach of the
      WHO Global Oral Health Programme.
AB  - The World Health Organization (WHO) "World Oral Health Report 2003" emphasized
      that despite great improvements in the oral health status of populations across
      the world, problems persist. The major challenges of the future will be to
      translate existing knowledge and sound experiences of disease prevention and
      health promotion into action programmes, this is particularly the case with
      developing countries that have not yet benefited from advances in oral health
      science to the fullest extent possible. The WHO Oral Health programme gives
      priority to research helping correct the so called 10/90 gap which relates to the
      fact that only 10% of funding for global health research is allocated to health
      problems that affect 90% of the world population. As knowledge is a major vehicle
      for improving the health of the poor in particular, the WHO Oral Health Programme
      focuses on stimulating oral health research in the developed and developing world
      to reduce risk factors and the burden of oral disease, and to improve oral health
      systems and the effectiveness of community oral health programmes. Building and
      strengthening research capacity in public health are highly recommended by WHO
      for effective control of disease and the socioeconomic development of any given
      country.

PMID- 15984132
TI  - Models for financing dental services. A review.
AB  - The aim of this review article is to give a brief description of the most
      important models for financing dental services, and then to describe the effects
      that the different models can have on patients' and dentists' behaviour. The
      advantages and disadvantages of the different models will be discussed. The first
      section focuses on the relationship between insured people and insurance
      providers. The justifications for a private insurance scheme and a public
      insurance scheme for dental treatment are discussed. A purely private insurance
      market for dental services will fail. This is because the benefits of a private
      dental insurance scheme are few in relation to the costs of having insurance, and
      because of the problem of adverse selection. There are also problems with public
      insurance schemes, for example, high transaction costs for collection of taxes
      and problems with cost containment as a result of moral hazard. The second
      section focuses on the relationship between the dentist and the patient, more
      specifically on how different remuneration schemes influence dentists' behaviour.
      The advantages and disadvantages of three types of remuneration scheme are
      discussed: fixed salary, per capita remuneration and pure fee-for-item
      remuneration. One important conclusion is that per capita payments secure
      effectiveness, while fee-for-item payments secure quality. With per capita
      payments there is a potential for patient-selection and undertreatment, while
      cost containment is a problem with fee-for-item payments. In order to counteract
      the adverse side-effects of each financing system, focus should be placed on the
      individual dentist in relation to ethics, norms and quality control.

PMID- 15984133
TI  - Dental caries experience of British children in an international context.
AB  - OBJECTIVES: To document data on current and past levels of dental decay in
      British children and compare trends with those in other countries, in Europe in
      particular. METHOD: Data were abstracted from multiple sources and collated and
      tabulated. RESULTS: The dental health of the majority of British children has
      improved dramatically since the early 1970s. Twelve-year-old children now have on
      average less than one decayed, missing (extracted) or filled tooth. Levels of
      dental decay in UK children at 5 and 12 years are among the lowest in the world.
      There are still marked inequalities in the dental decay experience of children
      between the territorial regions of the UK, high and low socio-economic groups,
      and regular and symptomatic dental attenders. Many children in areas of
      deprivation are either not motivated to seek dental treatment or experience
      barriers in obtaining it. In parallel with improvements in the dental health of
      the majority of children, the proportion of UK adults who have no natural teeth
      has fallen from 37% to 12% over the past four decades. Total tooth loss is now
      confined almost entirely to individuals over 45 years of age. Most of the
      improvements in children's dental health are attributable to environmental
      factors, in particular the widespread availability of fluoride containing
      toothpastes since the 1970s. There are clear benefits from fluoridation of public
      water supplies over and above those attributable to other factors. CONCLUSIONS:
      The findings suggest initiatives should be directed to bringing children from
      deprived backgrounds under the umbrella of dental care. To help alleviate the
      inequalities in dental health, water fluoridation should be implemented, in urban
      industrial areas in particular, where levels of dental decay are still
      unacceptably high.

PMID- 15984134
TI  - Increasing inequalities in the distribution of dental caries in the Brazilian
      context in Finland.
AB  - OBJECTIVE: To document the process of concurrent decline and polarization of
      dental caries distribution in the Brazilian context. BASIC RESEARCH DESIGN:
      Ecologic assessment of dental outcomes of surveys performed in 1998 and 2002, and
      several covariates using data aggregated at city-level. PARTICIPANTS: 9,327
      (1998) and 5,722 (2002) 12-year-old schoolchildren surveyed for oral health
      status in 131 and 34 towns respectively of the state of Sao Paulo, Brazil. MAIN
      OUTCOME MEASURES: DMFT index and Gini coefficient for caries distribution.
      RESULTS: The DMFT index declined from 3.72 in 1998 to 2.52 in 2002, while the
      Gini coefficient for the distribution of caries increased from 0.479 to 0.565. An
      improved profile of socio-economic standings, preventive dental treatment, access
      to fluoridated tap water and initiatives of dental education associated
      significantly with reduced levels of caries distribution. However, as these
      conditions were non-homogeneously distributed in the population, they are also
      associated with increasing levels of inequality in the distribution of caries.
      These observations indicate that there is room for further reduction of caries
      levels, by targeting the expansion of dental services and access to fluoridated
      water to groups and areas with higher levels of needs. CONCLUSIONS: Improved
      characterisation of the skewed distribution of caries experience demands that
      monitoring of the inequality in the distribution of caries by statistics such as
      the Gini coefficient be used. This information will inform programmes aimed at
      reducing levels of caries without reinforcing inequalities in the experience of
      the disease, a strategy that may contribute to the development of socially
      appropriate programmes of oral health promotion.

PMID- 15984135
TI  - Can dental epidemiological information be gathered during routine dental
      examinations by general dental practitioners?
AB  - OBJECTIVE: To assess the feasibility of gathering dental epidemiological
      information by General Dental Practitioners during routine dental examinations.
      DESIGN AND SAMPLE: Ten General Dental Practitioners (GDPs) and five Community
      Dental Officers (previously trained as dental examiners for epidemiological
      purposes) performed dental examinations of the same 10 volunteer adult patients
      in order to record decayed, missing and filled teeth. RESULTS: Agreement assessed
      by the kappa statistic showed that both the previously trained dental examiners
      and the GDPs assessed tooth conditions other than tooth decay consistently.
      Furthermore, all of the GDPs were within the range of findings of the previously
      trained dental examiners for missing teeth and total DMFT score. Eight of the 10
      GDPs were within the range of findings for the previously trained dental
      examiners' assessments of which teeth were filled and seven were within the range
      for decayed teeth. However, the previously trained dental examiners were more
      consistent in classifying teeth as decayed than the GDPs. CONCLUSION: Obtaining
      adult oral health data during elective dental consultations in General Dental
      Practice as a means to gather dental epidemiological information for adults is
      feasible.

PMID- 15984136
TI  - Dental check-ups in 31-year-olds in relation to optimism and life satisfaction.
AB  - OBJECTIVE: To analyse the impact of optimism and life satisfaction on dental
      check-ups. BASIC RESEARCH DESIGN: A cross-sectional study. PARTICIPANTS: The data
      used in this study consists of a postal questionnaire sent to the members of the
      1966 Birth Cohort in Northern Finland. The number of replies totalled 8,690,
      giving a response rate of 75.3%. MAIN OUTCOME MEASURES: The subjects were
      classified into two categories according to frequency of dental check-ups: those
      who went for check-ups at least once in two years and those who went more rarely.
      A Life Orientation Test was used to measure optimism. Life satisfaction was
      measured using a single question. The other explanatory variables were gender,
      marital status, education, incomes and employment status. Multivariate analyses
      were performed using log-binomial regression models. RESULTS: Independent of
      other factors, life satisfaction among women and optimism among men was
      associated with dental check-ups. Links between socioeconomic factors and dental
      check-ups were weaker than anticipated. CONCLUSIONS: The results suggest that not
      only socioeconomic factors but also psychosocial aspects need to be taken into
      account in planning successful dental health policy.

PMID- 15984137
TI  - Dental health of prisoners in the north west of England in 2000: literature
      review and dental health survey results.
AB  - BACKGROUND: A caries prevalence study of prisoners in the North West of England
      was conducted to allow comparisons with results of the 1998 United Kingdom Adult
      Dental Health Survey. METHOD: A random sample of prisoners in the North West of
      England was interviewed and examined using the same criteria as the 1998 United
      Kingdom Adult Dental Health Survey. RESULTS: From a random sample of 316
      prisoners, 279 (88%) were interviewed and 272 (86%) received a dental
      examination. Prisoners enter prison with twice as many decayed teeth (mean 4.2)
      than found in the general population in the North West of England (mean 1.9).
      Prisoners also have fewer restored teeth. There was little difference between the
      mean DMFT of adult male prisoners and young offender male prisoners. There was
      little difference in the mean DMFT of those in prison for more or less than two
      years. CONCLUSIONS: Prisoners in the North West of England had more decayed or
      unsound teeth, and fewer restored teeth than both non-institutionalised adults in
      the North West of England and social classes IV and V in England. Attempts to
      improve the effectiveness and efficiency of the Prison Dental Service in the
      North West of England may render the prison population dentally fit more
      speedily.

PMID- 15984138
TI  - A staged intervention dental health promotion programme to reduce early childhood
      caries.
AB  - OBJECTIVE: This paper reports the results of a community trial to assess the
      effects of a multi-stage dental health promotion programme in reducing Early
      Childhood Caries (ECC). RESEARCH DESIGN: Two health districts (Primary Care
      Groups) were matched for dental disease levels and socio-demographic factors. One
      was randomly allocated to be the test Primary Care Group (PCG), the other the
      control PCG. Children in the test PCG received a series of interventions to
      support positive dental health behaviour from the age of 8 to 32 months.
      Interviews were conducted with parents of children aged 21 months and clinical
      examinations were undertaken on a larger cohort of children aged 3-4 years in
      test and control PCGs. SETTING: The interventions were gift bags containing a
      trainer cup, toothpaste containing 1,450 ppm F and toothbrush, and advice given
      to the children's parents on attendance at designated clinics and medical
      practices and further paste and brushes posted to the children's homes. Parents
      were interviewed on the telephone. Examinations took place at Children's Centres
      and nursery departments attached to primary schools. OUTCOME MEASURES: Severity
      and prevalence of ECC and general caries and proportion of parents reporting
      adopting dentally healthy behaviours. RESULTS: In the test PCG the prevalence of
      ECC in children who had received the interventions was 16.6% compared with 23.5%
      of children in the control area, a reduction of 29% (p=0.003). The mean dmft
      (1.17) and prevalence of general caries experience (28.7%) in the test children
      were also significantly lower than for children in the control PCG (1.72: 39.2%)
      (p=0.001). Analysis from a community perspective, which included data from all
      children examined in both areas, showed the prevalence of ECC in the test and
      control PCGs was 21.3% and 22.8% respectively and the mean dmft 1.47 and 1.72.
      The proportion with general caries experience remained statistically significant
      in favour of the test area 33.8% vs 39.9% (p=0.01). Parents in the test PCG were
      more likely to report cessation of bottle use (33% vs 18%), use of sugar-free
      drinks (49% vs 24%), commencement of brushing before first birthday (45% vs 27%)
      and twice daily brushing (52% vs 34%). CONCLUSION: The parents who received this
      multi-stage intervention were more likely to report adoption of three positive
      oral health behaviours; using a trainer cup from one year of age, using safe
      drinks and brushing twice daily with a fluoride toothpaste. The programme failed
      to reduce the prevalence of ECC in the community but the prevalence of ECC and
      general caries experience among the children who participated was less than among
      children in the control PCG.

PMID- 15984139
TI  - The dogged scientist, the old lab vial, and the quest to stop cancer.

PMID- 15984140
TI  - Zapping cancer cells.

PMID- 15984141
TI  - [The radial artery in the myocardial revascularization, analysis of the patient
      subjects].
AB  - INTRODUCTION: The use of arterial grafts in the myocardial revascularization
      procedures has grown more popular due to their long-term patency compared with
      that of the great saphenous vein. The aim of this retrospective study was to
      assess our experience and first results in the group of patients who had
      underwent revascularization procedures using their radial artery. MATERIAL AND
      METHODOLOGY: Between 7/2000-2/2004, 51 patients of acceptable age, aged 69.0 +/-
      9.0 (42-82), underwent the revascularization procedure using the radial artery in
      combination with the left or right arteria mammaria interna. The angiographic
      examinations were conducted in 44 patients (86.3%), 5 patients refused to undergo
      their control angiographic examinations. Two patients exited a few months
      following their surgery, however there was no obvious connection with the use of
      the radial artery graft. RESULTS: Out of 44 patients (86.3%), who had their
      control angiographic examination completed, 9.4 +/- 9.8 months later, on average,
      (1-38 months), 5 patients (11.4%) suffered from the RA occlusion. In 4 patients,
      the occlusion was located at the branching site off the aorta, in 1 patient the
      occlusion was located at the site of the anastomosis with the left arteria
      mammaria interna. The total patency of the radial artery grafts reached 89%.
      CONCLUSION: The use of the radial artery in myocardial revascularization
      procedures has proven safe, associated with lower complication rates connected
      with its collection. Furthermore, the procedures result in a good short and mid
      term graft patency confirmed also on the control angiographic examinations.

PMID- 15984142
TI  - Fast track concepts and multimodal rehabilitation in colorectal surgery.

PMID- 15984143
TI  - [Therapeutically options for primary and secondary hepatic malignancies].
AB  - Therapeutically options for the treatment of patients with primary hepatic
      malignancies have grown in recent years. Apart from liver resection and organ
      transplantation, representing the only curative strategies for primary hepatic
      malignancies, a variety of palliative procedures have been introduced. Some of
      these result in extended patient survival. However, the combination of a
      malignant disease and an irreversible organ damage remains to be the main problem
      in the majority of patients with primary liver Cancer. Liver resection is the
      only curative therapy for patients with isolated hepatic colorectal metastases
      and can be performed with low morbidity and mortality if a correct indication and
      a standardized procedure is applied. In case of intrahepatic tumour recurrence re
      resection is indicated as long as extrahepatic metastases can be excluded. In
      patients with primary unresectable metastases a downstaging-chemotherapy, two
      stage hepatectomy or portal vene embolization might result in a secondary
      respectability. Locally ablative procedures are being evaluated at present, in
      the palliative Situation survival can be prolonged. In the future multimodal
      therapeutic approaches will dominate the treatment of primary and secondary
      hepatic malignancies.

PMID- 15984144
TI  - [Prevention, diagnosis and treatment of iatrogennic lesions of biliary tract
      during laparoscopic cholecystectomy. Management of papila injury after invasive
      endoscopy. Part 1. Prevention and diagnosis of bile duct injuries].
AB  - INTRODUCTION: Endoscopic invasive procedures in 70th and 80th years leaded to
      decrease reoperations on biliary tree. Iatrogenic injury of the biliary tract
      have increased in incidence in the first decade with the introduction of
      laparoscopic cholecystectomy. Athough a number of factors have been identified
      with a high risk of injury ( and number of technical steps have been emphasized
      to avoid these injury, the incidence of the bile duct injury has reached at least
      double the rate observed with open cholecystectomy. Cholecystectomy is most
      frequently performed abdominal operation and the most serious complication
      associated with this procedure is accidental injury to the common bile duct (0.3
      0.4%). This preventable technical error has tradicionally been thought to occur
      in one or more of three situations: 1. When the operator attempts to clip or
      ligate a bleeding cystic artery and also clips the common hepatic duct (Fig. 3a).
      2. When too much traction has been exerted on the gallbladder so that the common
      bile duct has tented up into an albow, which was either tied off with ligature or
      clipped (Fig. 3b). 3. When anatomic anomalies were not recognized and the wrong
      structure is divided, for example, when the cystic duct winds anterior to the
      common bile duct and enters on the left side, or when the cystic duct joins the
      right hepatic duct rather than the junction of the common hepatic and the common
      bile ducts (Fig. 1, 2, 3cd). In anatomical incertain cases is discussed about
      cholangiography and cholecystocholangiography during laparoscopy cholecystectomy.
      Most patients sustained a bile duct injury are recognized in the weeks folloving
      laparoscopic cholecystectomy. Careful preoperative preparation should include
      control of sepsis by draining any bile collections or fistulas and komplete
      cholangiography. Long-term results are best achieved in specialized hepatobiliary
      centres performing biliary reconstruction with a Roux-Y hepaticojejunostomy.
      Success rates over 90% have been reported from several centres to date with
      intermediate follow-up. Papila injury increased with introduction of a invasive
      endoscopy. Risk of deadly retroperitoneal inflamation is very high. Injury
      require same surgery procedure as duodenum injury. OWN EXPERIENCES: In an article
      a review of experiences of the 1st surgery department of General hospital in
      Prague since 1971 in 1 017 reoperations on biliary tree was carried out. There
      was in 311 patients 164 hepatohepatostomies and 147 hepaticojejunostomies used
      (Tab. 1). By laparoscopic injuries were high hilar injuries (Bismuth IV) in last
      decade and hepaticojejunostomy was done in all cases. Died 6%, long term results
      are acceptable by injured patients with hepaticohepaticostomies in 70%, by
      hepaticojejunostomies in 90%. Reoperated were 10% patients (Tab. 1). Remnant
      patients were dilated endoscopicaly. Postoperatively morbidity was high, above
      26%. In years 1995-2003 were 8 patients with papila injury and inflamation in
      retroperitoneum operated as a injured duodenum (Tab. 2). CONCLUSIONS: Better
      experiences with treatment of injured biliary tree and papila are in centres
      interested in hepatobilliary surgery which knowledge anatomy of hilus of liver
      and can make wide hepaticojejunostomy. Transfer of drained injured patient to
      centre is possible.

PMID- 15984145
TI  - [Prevention, diagnosis and surgical treatment of injuries of the biliary tract
      during laparoscopic cholecystectomy. Treatment of papilla injuries caused by
      invasive endoscopy. Part 2. Surgical treatment of biliary tract injuries].
AB  - INTRODUCTION: Introduction of endoscopic invasive procedures in the 70th and 80th
      years leaded to decrease reoperations on biliary tree. latrogenic injury of the
      biliary tract have increased in incidence in the first decade with the
      introduction of laparoscopic cholecystectomy. Athough a number of factors have
      been identified with a high risk of injury (and number of technical steps have
      been emphasized to avoid these injury, the incidence of the bile duct injury has
      reached at least double the rate observed with open cholecystectomy. Most
      patients that sustained a bile duct injury are recognized in the weeks following
      laparoscopic cholecystectomy. Careful preoperative preparation should include
      control of sepsis by draining any bile collections or fistulas and complete
      cholangiography. Long-term results are best achieved in specialized hepatobiliary
      centers performing biliary reconstruction with a Roux-Y hepaticojejunostomy.
      Success rates over 90% have been reported from several centres to date with
      intermediate follow-up. Introduction of an invasive endoscopy. Very dangerous is
      injury after endoscopic papilotomy. OWN EXPERIENCES: In an article of a review of
      experiences of the Ist Department of Surgery of General hospital in Prague since
      1971 in 1 017 reoperations on biliary tree has been carried out. There were in
      311 patients 164 hepato-hepatostomies and 147 hepaticojejunostomies used (Tab.
      1). By laparoscopic injuries in the last decade were hilary injuries (Bismuth IV)
      and hepaticojejunostomy was done in all cases. Died 6%, long-term results are
      acceptable by injured patients with hepatico-hepaticostomies in 70%, by
      hepaticojejunostomies in 90%. Reoperated were 10% patients. Remnant patients were
      dilated endoscopically. Postoperatively morbidity was high, above 26%. In years
      1995-2003 were 8 patients with papila injury and inflammation in retroperitoneum
      operated as a injured duodenum (Tab. 2). CONCLUSIONS: Better experiences with
      treatment of injured biliary tree and papila are in centres interested in
      hepatobiliary surgery which know anatomy of hilus of the liver and can see wide
      hepaticojejunostomy. Transfer of drained injured patient to centre is possible.

PMID- 15984146
TI  - [Laparoscopy-assisted colonoscopic polypectomias].
AB  - We present the method of laparoscopicaly assisted polypectomia as yet another
      option for management of large and poorly accessible polyps of the large
      intestine. The above method has been applied in 13 cases in 10 patients. In our
      study group, no perforations of the intestinal wall have occurred. The above
      procedure has been assessed as of minor stress for the patient.

PMID- 15984147
TI  - [Cooperation between a surgeon and a gastroenterologist in the management of
      vascular complications of the liver cirrhosis].
AB  - AIM: The aim of this work was to confirm indications for surgical procedures in
      cases of relapsing bleeding from oesophageal varices as a consequence of the
      liver cirrhosis. METHODOLOGY: Based on the retrospective study of the
      endoscopical examinations results and the patient records, the criteria of the
      patient selection for the surgical procedure, the type of the surgical procedure,
      the postoperative complications and the long-term assessment, were revised.
      RESULTS: During the six-year period, 7625 gastrofibroscopies were conducted. In
      this group, the oesophageal varices were diagnosed in 107 males and 47 females.
      In 76 males and 31 females the varices did not bleed. In 31 males and 16 females
      the varices did bleed and were sclerotised. In this subgroup, in 24 males and 13
      females the varices were eradicated or moved from the Paquet grade 3-4 to 1-2. In
      3 females and 7 males the sclerotherapy was not successful and the patients
      continued to bleed. Five males underwent surgery and 2 males and 3 females
      exsanguinated without surgery. The following surgical procedures were completted:
      3x Warren anastomoses, 1x Linton anastomosis and 1x resection of the
      duodenojejunal arcuation. One patient exited due to the liver failure.
      CONCLUSION: The sclerotherapy failed in 21.3% patients. Half of them
      exsanguinated. Only patients in the Child-Pugh A and B functional stage are
      indicated for the elective surgical procedure in cases of bleeding relapses
      following the sclerotherapy, varices of the gastric fundus and haemorrhaging
      gastropathy. Ablation is the method of choice in cases of emergency.

PMID- 15984148
TI  - [Carcinoids of the appendix].
AB  - The appendical carcinoids represent a heterogeneous group of tumors of different
      morphology, biological features and treatment. Our study aims to inform clinical
      practitioners, mainly surgeons and oncologists, about individual types of the
      appendical carcinoids, which are considered the most frequent carcinoid tumors
      the clinical practitioners come into contact with at all levels of the hospital
      care. Our work describes the types of the appendical tumors from the histological
      point of view, as well as from the prognostic and therapeutical points of view.
      At the end of the study report, a brief table summarizing the most important
      features of the individual histological types of the appendical carcinoids, is
      attached.

PMID- 15984149
TI  - [Options for combining surgical and endovascular techniques in the management of
      large aneurysms and dissections of the thoracic aorta].
AB  - The surgical management of aneurysms and dissections of the thoracic aorta, as
      well as their endovascular management, all have their technical and medical
      limits. The aim of this work is to point out possibility for combination of the
      both treatment methods and to share our first practical experience with this
      procedure. The procedures conducted have been divided into the following groups:
      combined procedures, where the surgical part enables implantation of the
      stentgraft into the descending aorta or is managing imperfect results of such
      implantations, procedures, where combining the surgical and endovascular
      treatment lowers operational stress of the patient, as the extracorporeal
      circulation and the circulation arrest are not required, procedures, where
      advantages of both the surgical treatment in the region of the aortic arch and
      the endovascular treatment in the region of the descending aorta, are combined.
      Using the combination of both the surgical and endovascular techniques in the
      management of the large aneurysms and dissections of the thoracic aorta, appears
      to be a perspective method. The patient may benefit from its lower perioperative
      risk rates and lower postoperative morbidity rates. A good long-term effect of
      the above treatment method may be expected, however, it has to be verified in
      long-term patient studies.

PMID- 15984150
TI  - Wisconsin collaborative develops performance measures.

PMID- 15984151
TI  - Targeted employee training lowers registration error rate.
AB  - The registration error rate at the University of Alabama Health Services
      Foundation was running about 30%, and that was having a negative impact on both
      billing and collections operations. The health system created a process to
      identify the employees committing the most errors, and then individual workers
      were provided with additional information and training ro help improve their
      accuracy. The result was a dramatic performance improvement.

PMID- 15984152
TI  - Software points out where performance needs improvement.
AB  - Quality improvement analysts are accustomed to running reports--lots of them--to
      identify areas of hospital activity that can use improvement. The work of
      calculating performance rates and comparing those to national benchmarks is time
      consuming and somewhat tedious. It doesn't have to be that way.

PMID- 15984153
TI  - Washington, DC, clinic to increase efficiency of diabetes care.
AB  - La Clinica del Pueblo is about to take a leap forward with the help of CareFirst
      BlueCross BlueShield, a major insurer covering the District of Columbia. The
      company is providing 360,000 dollars in funding over three years for the clinic
      to implement a cutting-edge system for treating patients with diabetes.

PMID- 15984154
TI  - Antibiotic cycling can reduce resistance, but it may cost more--in the short run.
AB  - You may be bored reading about antibiotic resistance, but what about a study that
      shows you a way to help attack the problem?

PMID- 15984155
TI  - Effects of nitric oxide synthase inhibitors on porcine oocyte meiotic maturation.
AB  - As an important biological messenger, nitric oxide (NO) exhibits a wide range of
      effects during physiological and pathophysiological processes, including
      mammalian oocyte meiotic maturation. The present study investigated whether NO
      derived from two nitric oxide synthase (NOS) isoforms, inducible NOS (iNOS) or
      endothelial NOS (eNOS), is involved in the meiotic maturation of porcine oocytes.
      Meanwhile, the cumulus cells' function in meiotic maturation and their
      interaction with oocyte development and degeneration were also investigated using
      cumulus-enclosed oocytes (CEOs) and denuded oocytes (DOs). Different inhibitors
      for NOS were supplemented to the medium. Cumulus expansion, cumulus cell DNA
      fragmentation and oocyte meiotic resumption were evaluated 48 h after incubation.
      Aminoguanidine (AG), a selective inhibitor for iNOS, suppressed cumulus expansion
      and inhibited CEOs to resume meiosis (p < 0.05), but did not inhibit cumulus cell
      DNA fragmentation. Both Nomega-nitro-L-arginine (L-NNA) and Nomega-nitro-L
      arginine methyl ester (L-NAME), inhibitors for both iNOS and eNOS, delayed
      cumulus expansion, inhibited cumulus cell DNA fragmentation and inhibited CEOs to
      resume meiosis. Such effects were not seen in DOs. These results indicate that
      iNOS-derived NO is necessary for cumulus expansion and meiotic maturation by
      mediating the function of the surrounding cumulus cells, and eNOS-derived NO is
      also involved in porcine meiotic maturation.

PMID- 15984156
TI  - Influence of seminal plasma PSP-I/PSP-II spermadhesin on pig gamete interaction.
AB  - The seminal plasma PSP-I/PSP-II spermadhesin is able to preserve, in vitro, the
      viability of highly extended boar spermatozoa, suggesting it might be used as a
      suitable ameliorator for the damaging effects of sperm handling, including in
      vitro fertilization. However, little is known about the ligand capability of PSP
      I/PSP-II as regards the zona pellucida (ZP) or its possible role in gamete
      interaction. The present study evaluated the effect of the presence of PSP-I/PSP
      II (1.5 mg/ml) during in vitro oocyte maturation and also during co-incubation of
      frozen-thawed boar spermatozoa with either immature (IM) or in vitro matured
      (IVM) oocytes, either enclosed by cumulus cells or denuded. Exposure of the
      gametes to the heterodimer during in vitro gamete co-incubation showed a
      significant blocking effect of sperm penetration rates and a decreased number of
      spermatozoa per oocyte in both IM and IVM denuded oocytes. Such an effect was not
      present in cumulus-enclosed oocytes, suggesting the effect could be mediated by
      exposed ZP receptors. In addition, when PSP-I/PSP-II was added to the IVM medium,
      oocyte maturation rates were significantly reduced. In conclusion, the results
      suggest that PSP-I/PSP-II, when present in vitro, blocks sperm-ZP binding.

PMID- 15984157
TI  - Haploidy influences Bak and Bcl-xL mRNA expression and increases incidence of
      apoptosis in porcine embryos.
AB  - The objective of this study was to determine developmental pattern, total cell
      number, apoptosis and apoptosis-related gene expression in haploid and diploid
      embryos following parthenogenetic activation. In vitro-matured porcine oocytes
      were activated by electrical pulses and cultured in the absence or presence of
      cytochalasin B for 3 h. Zygotes with two polar bodies (haploid) and one polar
      body (diploid) were carefully selected and were further cultured in NCSU 23
      medium containing 0.4% bovine serum albumin (BSA) for 7 days. The percentage of
      development to blastocyst stage was higher (p < 0.01) in the diploid than in the
      haploid parthenotes. In haploid blastocysts, average total cell number was
      significantly reduced (p < 0.05) and apoptosis was increased at day 7. The
      relative abundance of Bcl-xL and Bak mRNA in the diploid blastocysts was similar
      to that of in vivo-fertilized embryos. However, Bcl-xL was significantly
      decreased, and Bak mRNA was significantly increased (p < 0.05) in haploid
      parthenotes compared with the diploid parthenotes. These results suggest that the
      haploid state affects apoptosis-related gene expression which results in
      increased apoptosis and decreased developmental competence of haploid
      parthenotes.

PMID- 15984158
TI  - Characterization of aurora-a in porcine oocytes and early embryos implies its
      functional roles in the regulation of meiotic maturation, fertilization and
      cleavage.
AB  - Aurora-A is a serine/threonine protein kinase that plays important regulatory
      roles during mitotic cell cycle progression. In this study, Aurora-A expression,
      subcellular localization, and possible functions during porcine oocyte meiotic
      maturation, fertilization and early embryonic cleavage were studied by using
      Western blot, confocal microscopy and drug treatments. The quantity of Aurora-A
      protein remained stable during porcine oocyte meiotic maturation. Confocal
      microscopy revealed that Aurora-A distributed abundantly in the nucleus at the
      germinal vesicle stage. After germinal vesicle breakdown, Aurora-A concentrated
      around the condensed chromosomes and the metaphase I spindle, and finally, Aurora
      A was associated with spindle poles during the formation of the metaphase II
      spindle. Aurora-A concentrated in the pronuclei in fertilized eggs. Aurora-A was
      not found in the spindle region when colchicine or staurosporine was used to
      inhibit microtubule organization, while it accumulated as several dots in the
      cytoplasm after taxol treatment. In conclusion, Aurora-A may be a multifunctional
      kinase that plays pivotal regulatory roles in microtubule assembly during porcine
      oocyte meiotic maturation, fertilization and early embryonic mitosis.

PMID- 15984159
TI  - Embryos produced in vitro from bulls carrying 16;20 and 1;29 Robertsonian
      translocations: detection of translocations in embryos by fluorescence in situ
      hybridization.
AB  - Robertsonian translocation rob(16;20) in the heterozygous state was discovered in
      a subfertile bull of the Czech Siemmental breed. A chromosomal analysis of its
      family has shown that this dicentric fusion is formed de novo. The present
      experiments were designed to detect rob(16;20) and determine its incidence for in
      vitro produced embryos, using fluorescence in situ hybridization (FISH) and
      rob(1;29) as a detection control. To characterize semen of both bulls with the
      rob translocations, their sperm was examined for DNA integrity by the sperm
      chromatin structure assay (SCSA). For in vitro fertilization of oocytes,
      spermatozoa from a rob(16;20) bull carrier (Czech Siemmental breed) and those
      from a rob(1;29) bull carrier (Charolais breed) were used. Embryos at the 6- to 8
      cell stage were cultured in a vinblastine-supplemented medium for 17 h, and
      embryos at the blastocyst stage were cultured in a colcemide-supplemented medium
      for 4 h. The embryos were fixed in methanol and acetic acid with Tween-20.
      Painting probes for chromosomes 16 (Spectrum Green) and 20 (Spectrum Orange) and
      chromosomes 1 (Spectrum Orange) and 29 (Spectrum Green) were simultaneously
      hybridized. In the embryos derived from the rob(16;20) bull, the presence of this
      translocation was not detected. On the other hand, 52.5% of the embryos derived
      from the rob(1;29) bull were translocation carriers. There was no significant
      difference in the frequency of this translocation between early and advanced
      embryos.

PMID- 15984160
TI  - Transplantation of male pronucleus derived from in vitro fertilization of
      enucleated oocyte into parthenogenetically activated oocyte results in live
      offspring in mouse.
AB  - In this study, inter-strain reconstructed embryos were produced by combining the
      female pronucleus of Kunming mouse (white) with male pronucleus of C57BL/6 strain
      (black). Metaphase II (MII) oocytes of Kunming mouse were enucleated and the zona
      pellucida was removed. Then, the enucleated oocytes were inseminated by
      capacitated sperm of C57BL/6 mouse in vitro. At the same time, MII oocytes of
      Kunming mouse were artificially activated using strontium chloride solution,
      which did not contain cytochalasin B. Finally, we removed the male pronucleus
      derived from C57BL/6 sperm and injected it into a parthenogenetically activated
      one-pronucleus oocyte by micromanipulation. The reconstructed 2-cell embryos were
      transplanted into the oviducts of 22 foster mother mice, each receiving about 20
      embryos. In the end, seven healthy and live pups were born from one recipient.

PMID- 15984161
TI  - Production of rabbit chimeric embryos by aggregation of zona-free nuclear
      transfer blastomeres.
AB  - The objective of this study was to compare in vitro developmental capacity of
      zona-free aggregated rabbit chimeric embryos and the allocation of EGFP (enhanced
      green fluorescence protein) gene expression to the inner cell mass (ICM). We
      produced chimeric embryos by synchronous aggregation of zona-free blastomeres
      from embryonic cell nuclear transfer (EMB-NT) or somatic cell nuclear transfer
      (SC-NT) and blastomeres from normal zona-free embryos (N) at the 16-cell stage.
      In the control group, transgenic (TR) and normal zona-free embryos were used to
      produce chimeric embryos (TR<>N). EMB-NT embryos were produced by fusion of
      enucleated oocytes with embryonic cells, which were derived from 32-cell stage
      transgenic embryos bearing the EGFP gene. The SC-NT embryos were produced by
      fusing enucleated oocytes with cumulus cells, which were derived from homozygotes
      transgenic for the EGFP gene female oocytes at 16h post-coitum. Nuclei of
      transgenic blastomeres emitted a green signal under fluorescence microscopy. Zona
      free EMB-NT or zona-free SC-NT rabbit embryos, both with EGFP fluorescence, as
      well as TR and zona-free rabbit embryos with no fluorescence (EMB-NT<>N, SC
      NT<>N, TR<>N) were aggregated on day 2.5 and evaluated on day 5. The proportion
      of EMB-NT<>N embryos that developed to the blastocyst stage was significantly
      higher compared with SC-NT derived cells (p < 0.05), but significantly lower than
      in TR<>N chimeric blastocysts (p < 0.001). Similarly, a higher proportion (p <
      0.001) of EGFP-positive cells allocated to ICM of chimeric blastocysts was
      revealed in TR<>N chimeras (55%), compared with EMB-NT<>N (35%) and SC-NT<>N
      (21%). Our results indicate that synchronous chimeric embryos reconstructed from
      TR embryos were better able to develop and colonize the ICM area than EMB-NT and
      SC-NT embryos. In this study we have demonstrated for the first time that rabbit
      NT-derived embryos are able to develop into chimeric blastocysts and participate
      in the ICM area.

PMID- 15984162
TI  - Cell-cycle-dependent subcellular localization of cyclin B1, phosphorylated cyclin
      B1 and p34cdc2 during oocyte meiotic maturation and fertilization in mouse.
AB  - M phase or maturation promoting factor (MPF), a kinase complex composed of the
      regulatory cyclin B and the catalytic p34cdc2 kinase, plays important roles in
      meiosis and mitosis. This study was designed to detect and compare the
      subcellular localization of cyclin B1, phosphorylated cyclin B1 and p34cdc2
      during oocyte meiotic maturation and fertilization in mouse. We found that all
      these proteins were concentrated in the germinal vesicle of oocytes. Shortly
      after germinal vesicle breakdown, all these proteins were accumulated around the
      condensed chromosomes. With spindle formation at metaphase I, cyclin B1 and
      phosphorylated cyclin B1 were localized around the condensed chromosomes and
      concentrated at the spindle poles, while p34cdc2 was localized in the spindle
      region. At the anaphase/telophase transition, phosphorylated cyclin B1 was
      accumulated in the midbody between the separating chromosomes/chromatids, while
      p34cdc2 was accumulated in the entire spindle except for the midbody region. At
      metaphase II, both cyclin B1 and p34cdc2 were horizontally localized in the
      region with the aligned chromosomes and the two poles of the spindle, while
      phosphorylated cyclin B1 was localized in the two poles of spindle and the
      chromosomes. We could not detect a particular distribution of cyclin B1 in
      fertilized eggs when the pronuclei were initially formed, but in late pronuclei
      cyclin B1 was accumulated in the pronuclei. p34cdc2 and phosphorylated cyclin B1
      were always concentrated in one pronucleus after parthenogenetic activation or in
      two pronuclei after fertilization. At metaphase of 1-cell embryos, cyclin B1 was
      accumulated around the condensed chromosomes. Cyclin B1 was accumulated in the
      nucleus of late 2-cell embryos but not in early 2-cell embryos. Furthermore, we
      also detected the accumulation of p34cdc2 in the nucleus of 2- and 4-cell
      embryos. All these results show that cyclin B1, phosphorylated cyclin B1 and
      p34cdc2 have similar distributions at some stages but different localizations at
      other stages during oocyte meiotic maturation and fertilization, suggesting that
      they may play a common role in some events but different roles in other events
      during oocyte maturation and fertilization.

PMID- 15984163
TI  - Round spermatids stained with mitotracker can be used to produce offspring more
      simply.
AB  - Although both intracytoplasmic sperm injection (ICSI) and round spermatid
      injection (ROSI) are used in infertility treatments, the rate of offspring
      achieved with ROSI is low compared with that achieved with ICSI. The difficulty
      in correctly selecting round spermatids from testicular cells is one of the
      causes of this phenomenon. We easily selected live round spermatids from
      testicular cells stained with 20 nM MitoTracker, which visualizes mitochondria
      without killing the cell. Using this method, we divided round spermatids into
      three groups based on the polarization of their mitochondria, and performed ROSI.
      The rate of successful offspring achieved with MitoTracker-stained ROSI was the
      same in all groups. This indicates that changes in the polarization of
      mitochondria in round spermatids are not directly related to the developmental
      capacity of subsequently fertilized embryos. Because this staining has no harmful
      effects on embryo development, the selection of spermatids by MitoTracker under a
      fluorescence microscope should be useful in research into and the treatment of
      infertility.

PMID- 15984164
TI  - Asterosap-induced elevation in intracellular pH is indispensable for ARIS-induced
      sustained increase in intracellular Ca2+ and following acrosome reaction in
      starfish spermatozoa.
AB  - In the starfish, Asterias amurensis, the cooperation of three components of the
      egg jelly, namely ARIS (acrosome reaction-inducing substance), Co-ARIS and
      asterosap, is responsible for the induction of acrosome reaction. For the
      induction, ARIS alone is enough in high-Ca2+ or high-pH seawater, but, besides
      ARIS, the addition of either Co-ARIS or asterosap is required in normal seawater.
      Asterosap transiently increased both the intracellular pH (pHi) and Ca2+
      ([Ca2+]i), while ARIS slightly elevated the basal level of [Ca2+]i. However, a
      sustained elevation of [Ca2+]i and acrosome reaction occurred if sperm were
      simultaneously treated with ARIS and asterosap. EGTA inhibited the sustained
      [Ca2+]i elevation and acrosome reaction. The sustained [Ca2+]i elevation and
      acrosome reaction were highly susceptible to SKF96365 and Ni2+, specific blockers
      of the store-operated Ca2+ channel (SOC). These results suggest that sustained
      [Ca2+]i elevation, mediated by the SOC-like channel, is a prerequisite for the
      acrosome reaction. In high-pH seawater, ARIS alone induced a prominent [Ca2+]i
      increase and acrosome reaction, which were similarly sensitive to SKF96365. The
      acrosome reaction was effectively induced by ARIS alone when pHi was artificially
      increased to more than 7.7. Asterosap increased pHi from 7.6 +/- 0.1 to 7.7 +/-
      0.1. Furthermore, the sustained [Ca2+]i elevation and acrosome reaction, induced
      by a combination of ARIS and asterosap, were drastically inhibited by a slight
      reduction in pHi. Taking these results into account, we suggest that an asterosap
      induced pHi elevation is required for triggering the ARIS-induced sustained
      [Ca2+]i elevation and consequent acrosome reaction.

PMID- 15984165
TI  - Production of mouse by inter-strain inner cell mass replacement.
AB  - The developmental ability of reconstructed blastocysts from C57BL/6 strain mouse
      inner cell masses (ICMs) and Kunming strain mouse trophoblasts was assessed. The
      procedure of ICM replacement was as follows: C57BL/6 ICMs were separated from the
      blastocysts using immunosurgery. A slit was made in the zona pellucida of a
      Kunming blastocyst to allow its ICM to extrude. The C57BL/6 ICM was injected into
      the Kunming blastocoele, and the extruded Kunming ICM was cut off. The
      reconstructed blastocysts were able to re-expand (77%) and hatch (27.3%) in
      vitro. A total of 64 reconstructed blastocysts and 124 Kunming blastocysts were
      co-transferred into the uteri of 11 pseudopregnant Kunming mice, and an ICM
      replacement offspring was born. The results indicate that reconstructed embryos
      obtained by inter-strain ICM replacement have the ability to develop to term.
      This technique may provide a method to solve the pregnancy failure in
      interspecific cloning.

PMID- 15984166
TI  - Viable rat offspring derived from oocytes intracytoplasmically injected with
      freeze-dried sperm heads.
AB  - A 2 x 3 factorial designed experiment was conducted in order to examine whether
      freeze-dried rat spermatozoa can participate in full-term development following
      intracytoplasmic sperm injection (ICSI). A sperm suspension from cauda
      epididymides of Sprague-Dawley (SD) rats was prepared with or without ultrasonic
      treatment. The sonicated and non-sonicated sperm suspensions were processed for
      freeze-thawing (FT groups; 100 microl sample was cooled in liquid nitrogen vapor,
      stored for 1 day at--196 degrees C, and thawed in a 25 degrees C water bath) and
      freeze-drying (FD groups; 100 microl sample was frozen in liquid nitrogen for 20
      s, lyophilized for 6 h, stored at 4 degrees C for 2 days, and rehydrated with 100
      microl ultrapure water), or were subjected to immediate use for ICSI (fresh
      control groups). The sperm heads were microinjected into denuded SD oocytes using
      a piezo-driven micropipette 2-4 microm in diameter. The presumptive zygotes were
      transferred into oviducts of pseudopregnant Wistar female rats. Viable rat
      offspring were produced from all six experimental groups. Ultrasonic treatment of
      rat spermatozoa was effective in increasing the offspring rate (23.3% vs 6.7% in
      fresh control groups, 35.0% vs 7.6% in FT groups, 9.2% vs 2.5% in FD groups). The
      acrosomal region appeared to be intact even after ultrasonic FT and FD treatments
      as well as in the fresh controls, while the lateral dorsal region of the sperm
      membrane was more or less damaged in the sonicated, FT and FD samples. Thus, the
      successful participation of freeze-dried spermatozoa in full-term development was
      demonstrated by applying ICSI in the rat.

PMID- 15984167
TI  - Participation of the ubiquitin-proteasome pathway in rat oocyte activation.
AB  - The role of the ubiquitin-proteasome pathway (UPP) in mitosis is well known.
      However, its role in meiotic division is still poorly documented, especially in
      the activation of mammalian oocytes. In this study, the role of proteasome in the
      spontaneous and parthenogenetic activation of rat oocytes was investigated. We
      found that ALLN, an inhibitor of proteasome, when applied to metaphase II
      oocytes, inhibited spontaneous activation, blocked extrusion of the second polar
      body (PB) and caused the withdrawal of the partially extruded second PB. ALLN
      also inhibited the parthenogenetic activation induced by cycloheximide, but had
      no effect on the formation of pronuclei in activated eggs. In metaphase and
      anaphase, ubiquitin and proteasome localized to the meiotic spindle,
      concentrating on both sides of the oocyte-second PB boundary during PB extrusion.
      This pattern of cellular distribution suggests that UPP may have a role in
      regulating nuclear division and cytokinesis. Ubiquitin was seen to form a ring
      around the pronucleus, whereas proteasome was evenly distributed in the
      pronuclear region. Taken together, our results indicate that (1) UPP is required
      for the transitions of oocytes from metaphase II to anaphase II and from anaphase
      II to the end of meiosis; and (2) the UPP plays a role in cytokinesis of the
      second meiotic division.

PMID- 15984168
TI  - What is driving increasing child welfare caseloads in Ontario? Analysis of the
      1993 and 1998 Ontario incidence studies.
AB  - Rates of substantiated maltreatment documented by the 1993 and 1998 Ontario
      Incidence Studies of Reported Child Abuse and Neglect doubled between 1993 and
      1998. Although increasing public awareness and changes in investigation
      procedures appear to account for part of this change, the increase also reflects
      a significant shift in the types of maltreatment agencies are investigating and
      substantiating. Exposure to spousal violence has increased eightfold, and the
      proportion of neglect cases has more than doubled, whereas cases of sexual abuse
      are decreasing. The field requires a differentiated response to address the
      maltreatment-specific challenges underlying child welfare caseload increases in
      Canada.

PMID- 15984169
TI  - Covariates of length of stay in residential treatment.
AB  - This study explores variables associated with length of stay in a child welfare
      residential treatment center. The study followed three entry cohorts (416 boys)
      from admission through discharge. The researchers conducted event history
      analyses to examine the rates of discharge over time and the covariates of length
      of stay. They conducted analyses by discharge destination (reunified,
      transferred, or ran away). The results demonstrated that mental health issues
      slowed down rates of discharge for youth who were reunified or transferred. For
      children who left by running away, age and prior substance history were
      associated with faster rates of exit. These results have important public policy
      implications for improving the application of length of stay variables in
      planning and treatment.

PMID- 15984170
TI  - Fathers in child welfare: caseworkers' perspectives.
AB  - Five focus groups substantially agreed about the lack of paternal participation
      in child welfare services and the reasons for low paternal involvement. The
      groups had considerable disagreement about whether child welfare professionals
      should address this issue. Some caseworkers believed that all fathers and mothers
      should be treated identically with respect to services to be offered and time
      frames for services; other caseworkers thought that the special circumstances of
      some fathers, such as lack of child care experience, called for service
      approaches that differ from those for mothers. Another disagreement was whether
      more fathers would be more involved if services were gender sensitive, that is,
      if agencies provided male caseworkers for fathers and had father-only services.
      Much of the debate focused on pragmatic considerations (would gender-sensitive
      services improve paternal participation and outcomes?), although some
      participants were concerned about equity (would such services give fathers an
      advantage in disputed custody cases?).

PMID- 15984171
TI  - Accessibility and clarity of state child welfare agency mission statements.
AB  - The authors reviewed 40 mission statements guiding U.S. public child welfare
      practice for accessibility, clarity, and values. Nine of the 40 state
      administered child welfare agencies had not posted their missions on the Web as
      of October 2002, and 30 mission statements required a 12th-grade or college
      reading level for easy comprehension. The mission statements most often expressed
      the goals, values, and processes of safety, permanence, well-being, family
      preservation, cultural competence, self-sufficiency, and partnership. Mission
      statements can be an important tool for improving child welfare outcomes by
      providing direction; therefore, agency administrators should consider how clear
      and accessible their state agency mission statements are.

PMID- 15984172
TI  - Agony in the bones: arthritis is crippling more people, but there are nine key
      ways to beat the pain.

PMID- 15984173
TI  - The tyranny of experts.

PMID- 15984174
TI  - An autopsy won't end it.

PMID- 15984175
TI  - A nightmare scenario.

PMID- 15984176
TI  - Xylitol in the prevention of oral diseases.
AB  - Special needs populations such as the mentally disabled or developmentally
      disabled present a unique challenge for the dental professionals providing dental
      treatment. Among those challenges is oral health promotion through primary
      prevention of dental caries and periodontal disease. There are many barriers to
      adequate oral care for these special needs patients that include cost, physical
      limitations, low levels of perceived need and lack of dental knowledge by
      residents and staff, if the person resides in an institution. Primary prevention
      to maintain oral comfort and function for these patients is a priority to support
      their quality of life. Typical oral health problems of these patients include
      hyposalivation, root-surface caries, poor oral hygiene, a high prevalence of
      periodontal disease and dental caries. The purpose of this paper is to review
      information for the inclusion of xylitol in primary preventive regimens as an
      adjunct for the prevention of oral diseases for special needs patients.

PMID- 15984177
TI  - Racial differences in salivary sIgA concentrations in postmenopausal women.
AB  - The purpose of this study was to compare sIgA salivary concentrations between
      Caucasian and African-American postmenopausal women. The age, height, weight and
      history of hormone replacement therapy were recorded and the BMI was calculated
      for each individual. Whole, stimulated saliva was assayed for sIgA and total
      protein. Logistic regression analysis evaluated the relationships between the
      outcome variables. Total salivary sIgA and adjusted sIgA (adjusted for protein)
      concentrations were significantly higher in the African-American women (p<0.01).
      There were significant statistical correlations between sIgA concentrations and
      race (p<0.01). Our data suggest that racial differences in salivary sIgA
      concentrations in elderly women could be an important variable for planning
      future studies utilizing salivary samples as biological markers.

PMID- 15984178
TI  - What predicts oral health stability in a long-term care population?
AB  - The purpose of this study was to determine whether oral health stability was
      achievable over time for institutionalized elderly who routinely received
      comprehensive care and to examine the factors associated with stability. Records
      of 868 dentate nursing home residents, each with a minimum of 24 months
      continuous care, were analyzed to determine the number of services by type for
      each time period between periodic examinations. Presenting dental condition, age,
      gender, functional status, payer source and facility characteristics were tested
      as explanatory variables. Oral health status was considered stable when a
      resident had a "good checkup" (needing no further treatment), otherwise it was
      coded as unstable. Generalized estimating equations (GEE) were used to analyze
      predictors of stability over time. Stability over time was achieved in 44% of the
      study group and negatively associated with male gender, advanced age, and more
      initial treatment needs. The data show that high levels of initial unmet needs
      were associated with difficulty achieving oral health stability for
      institutionalized elderly who routinely received comprehensive care.

PMID- 15984179
TI  - Perceptions of dental care need among African-American elders: implications for
      health promotion.
AB  - The aim of this study was to assess perceived dental care need, actual clinical
      need and the relationship between these variables and care-seeking behavior among
      community residing African-American elders. A convenience sample of 146 elders
      responded to a survey and participated in oral screenings at six senior centers.
      Elders were categorized as needing routine dental care, some dental care, or
      urgent dental care. Most (61%) required dental care with one-fourth having urgent
      dental care needs. Elders reporting a problem tended to seek dental care more
      often within a year (38%) than those not reporting a problem (27%). Sixty-four
      percent did not currently have a dental provider. The majority (83%) rated their
      general health as being fair or good and few (9%) reported oral pain. These
      findings suggest developing health promotion programs that emphasize non-painful
      oral signs and symptoms, accompanied by associated general health implications
      that may compromise overall health.

PMID- 15984180
TI  - A self-reported survey of Alzheimer's centers in Southwestern Pennsylvania.
AB  - Directors of nursing at 23 nursing homes with Alzheimer's units in Southwestern
      Pennsylvania completed a self-reported survey of 12 questions. Responses from the
      self-administered questionnaires (100% response rate) revealed a wide variation
      in the staff categories assessing the oral health status of newly admitted
      residents with AD. The respondents described oral examinations that were
      incomplete when compared to the oral indicators listed in the Minimum Data Set.
      All nursing homes reported that oral hygiene was provided each day. The number of
      residents in a facility had a significant effect on the frequency of oral hygiene
      provided. Only 52% of the facilities reported yearly oral examinations for this
      population. According to the respondents, dental treatment was typically
      performed on-site. The oral health care costs were paid by Medicare, Medicaid,
      the residents/family members, or by other undescribed resources. Insufficient
      time, staff, and training, as well as uncooperative behavior, were identified as
      barriers to optimum oral health care for residents with AD. Additional staff,
      specialized training, and increased government reimbursement were suggested to
      improve the oral health care for this group of older adults. For future studies,
      review of medical records and on-site evaluation of the oral health care at these
      facilities should be required to verify the reported practices.

PMID- 15984181
TI  - [Acute mental disorders in children and adolescents held as hostages by the
      terrorists in Beslan].
AB  - Stress reactions were studied in 92 children and adolescents held as hostages by
      the terrorists in Beslan (September, 2004). A special feature of mental trauma in
      this group of hostages is its extraordinary severity and duration, marked
      physical exhaustion and dehydration, a high proportion of small children, high
      frequency of burns, wounds and traumas. All the examinees demonstrated main signs
      of acute stress reactions (ASR): disturbed consciousness, psychomotor disorders,
      emotional disorders and autonomic changes. Moreover, there were such ASR
      appearances as repeated experience of trauma, avoidance, dissociation and
      regressive symptoms, hallucinations and delusion. A very high frequency of
      anxiety, fear and sleep disorder was registered. Age-specific characteristics of
      ASR are shown: higher frequency and longer duration of disturbed consciousness in
      small children, inverse relation between the degree of emotional experience
      differentiation and the victim's age. More severe mental disorders develop in
      victims who have lost their relatives.

PMID- 15984182
TI  - [Age dynamics of mental disorders in neglected minors].
AB  - Three hundred and sixty socially maladapted 7-18 year old children have been
      studied. Their mental state was evaluated in 3 age groups: 7-10 years (60
      subjects); 11-14 years (202) and 15-18 years (98). The ICD-10 diagnosis of
      addictive behavior was established in 228 cases, mild cognitive disorders in 92;
      adaptation disorders in 61 and socialized and unsocialized disturbances of
      behavior--86 and 66 cases, respectively. As a rule, these disorders combined with
      neurotic ones. With age, social and school maladaptation advances, pathological
      drives and asocial behavior progress. Family history of mental diseases, social
      impacts such as lack of parent's or formal caregiver's control, and high
      frequency of mental disorders in children are risk factors for neglect.

PMID- 15984183
TI  - [Use of a 3-oxypiridine antioxidant in combined therapy of patients with partial
      epilepsy].
AB  - Fifty-four patients with partial epilepsy (age 18-50 years, 26 males and 28
      females, illness duration from 6 months to 18 years) have been examined.
      Idiopathic epilepsy was diagnosed in 7 patients, symptomatic in 36, cryptogenic
      in 11. The control group comprised 22 sex- and age-matched individuals. All the
      patients underwent computerized EEG and pharmaco-EEG testing, MRI or CT of the
      brain. Follow-up duration was from 6 months to 2.5 years. An antioxidant
      therapeutic course was conducted during 30 days on the background of the basic
      anticonvulsive therapy with carbamazepine (finlepsin-retard 200) received in
      individual dosages. Computer EEG analysis was made using "BRAINWIN" soft
      (Mitrofanov A.A., "Statokin", Moscow). To estimate the effect of the medications
      on bioelectric brain activity, methods of spectral and coherent EEG analysis,
      localization of equivalent dipole source of paroxysmal activity were applied.
      After a 30-day course of combined therapy with carbamazepine (finlepsin-retard
      200) and antioxidant Mexicor, inhibition of generator activity of limbic and
      hypothalamic as well as stem and cerebellum structures and displacement of
      generator zones into cortical hemisphere structures were observed that may be
      explained by enhancement of determinant foci of the cortical structures in
      inhibition of secondary foci. It may be considered as a favorable prognostic
      factor, which reduces probability of the secondary generalization of partial
      epileptic seizures.

PMID- 15984184
TI  - [Normoxic curative compression in combined treatment of hypertensive
      encephalopathy].

PMID- 15984185
TI  - [Tolcapone treatment of late stages of Parkinson's disease].

PMID- 15984186
TI  - [Neuromultivit in the treatment of serous meningitis in children].

PMID- 15984187
TI  - [Nonspecific brain systems and rehabilitation of children with cerebral palsy].
AB  - Basing on a long-term investigation of 157 children with spastic forms of
      cerebral palsy, regressive mathematical models of motor development have been
      worked out, taking into account a degree of severity and outcome of the disease.
      Mathematical patterns, reflecting dysneuroontogenesis of suprasegmental
      regulation system, are obtained. Complex electroencephalographic,
      electromyographic and vegetologic data demonstrated a role of limbic and
      reticular complex of intersystemic and intrasystemic disintegration in the
      reduction of adaptability and rehabilitation potential in patients with cerebral
      palsy. Basic concepts of adaptoregulatory approach to rehabilitation potential,
      basing on the necessity of nonspecific brain system correction for creation of
      neurodynamic suprasegmental and segmental adaptor energetic and adaptor
      immunoregulative premises for forming and providing specific psychomotor
      functions, are presented.

PMID- 15984188
TI  - [The 60th anniversary of the Institute of Psychiatry-Mental Health Research
      Center of the Russian Academy of Medical Sciences].

PMID- 15984189
TI  - [Coaxil therapy of affective disorders in brain vascular pathology].

PMID- 15984190
TI  - [A rare form of primary headache].

PMID- 15984191
TI  - [Molecular genetic aspects of epilepsy].

PMID- 15984192
TI  - Recent developments of derivative spectrophotometry and their analytical
      applications.
AB  - Articles about the development of derivative spectrophotometric methods and
      analytical applications of derivative spectrophotometry (DS) published in the
      last nine years (since 1994) are reviewed.

PMID- 15984193
TI  - High-throughput photometric titrimetry based on a feedback-based and subsequent
      fixed triangular wave-controlled flow ratiometry.
AB  - The principle of flow ratiometry for high-throughput titration, which we recently
      proposed for potentiometric titration, was extended to photometric titration. The
      flow rate (FB) of a base solution containing an acid-base indicator was linearly
      varied in response to a control voltage (Vc) generated from a computer. With the
      total (acid + base) flow rate (FT) being kept constant, the base solution was
      merged with an acid solution, which was aspirated to the confluence point at a
      flow rate of FT - FB. Downstream, the relative transmittance of the mixed
      solution was measured at the maximum absorption wavelength of the base form of
      the indicator. Initially, a feedback-based control was applied, where the scan
      direction of Vc was reversed from upward to downward, and vice versa, whenever
      the transition of the indicator at the equivalence point (EP) was sensed. Next,
      the scan range of V. was further limited to the range just around EP by using
      fixed triangular waves. These processes avoided scanning in a range of no
      interest. Thus, an unprecedentedly high throughput rate (maximally 34 titrations
      per minute, corresponding to 1.76 s per titration) was realized with reasonable
      precision (RSD < 0.5%).

PMID- 15984194
TI  - Prestaining method as a useful tool for the agarose gel electrophoretic detection
      of polymerase chain reaction products with a fluorescent dye SYBR gold nucleic
      acid gel stain.
AB  - Three staining methods using SYBR Gold Nucleic Acid Gel Stain (SYBR Gold) as a
      fluorescent dye were evaluated for the agarose gel electrophoretic detection of
      DNA. The methods involve prestain, in-gel stain, and poststain methods. DNA
      markers and polymerase chain reaction (PCR) products obtained by minisatellite
      variant repeat-PCR (MVR-PCR) amplification in a D1S8 locus were used as model DNA
      and practical samples, respectively. Among the three methods tested under the
      usual electrophoretic conditions, a prestain method using a 10000-fold diluted
      SYBR Gold solution showed most excellent features regarding cost and rapidity to
      use with good stainability and resolution over loaded DNA amounts of about 98 ng
      to 300 ng. The prestain method was found to be applicable to the analysis of DNA
      in MVR-PCR products from a human hair root.

PMID- 15984195
TI  - Identification of gas emanated from human skin: methane, ethylene, and ethane.
AB  - We investigated whether methane, ethylene and ethane gas can be detected in gas
      emanating from human skin, which is called skin gas. Skin gas was collected with
      a homemade stainless-steel trap system, which was cooled with liquid nitrogen,
      and analyzed with a gas chromatograph fitted with a flame ionization detector
      (FID). Skin-gas samples were obtained by covering a hand for 30 min with a
      polyfluorovinyl bag in which pure helium gas was introduced. The bag, the trap
      system and GC were set up online to avoid any contamination by air. Methane,
      ethylene and ethane in skin gas were successfully collected at an average amount
      emanated for 30 min (from ten subjects) of 150 +/- 63, 20 +/- 11 and 17 +/- 8
      [mean +/- SD] pg/cm2, respectively.

PMID- 15984196
TI  - A microporous membrane-based continuous generation system for trace-level
      standard mixtures of atmospheric gases.
AB  - A reliable and convenient system to generate accurate and stable standard gas
      mixtures of various atmospheric compounds at parts-per-billion levels has been
      developed. The system is of simple design; the generator is a coil consisting of
      an inner tube of microporous polytetrafuluoroethylene (PTFE) membrane tubing and
      an outer tube of silicone tubing. An aqueous solution of the given compound
      continuously flows through the inner microporous tube and the purge gas flows
      through the annulus between the inner and outer tubes. In addition to the
      generation of gas mixtures based on Henry's law, the proposed flow-type system
      offers generation based on chemical reactions, leading to a distinct advantage of
      the availability of continuous sources of various compounds. The generation
      system was tested for preparing standard gas mixtures of HCHO and H2O2 on the
      basis of Henry's law, and those of HNO2, NO, and SO2 on the basis of chemical
      reactions. A stable generation of the desired low concentrations of various kinds
      of gas mixtures can be readily achieved by adjusting the concentration of the
      solution without the use of high-dilution flow.

PMID- 15984197
TI  - Local structure of nitrogen atoms in a porphine ring of mesophenyl substituted
      porphyrin with an electron-withdrawing group using X-ray photoelectron
      spectroscopy and X-ray absorption spectroscopy.
AB  - This study investigated the protonation of nitrogen atoms in porphyrins with meso
      phenyl p-substituted by an electron-withdrawing group using N 1s X-ray
      photoelectron spectroscopy (XPS), the N K X-ray absorption near-edge structure
      (XANES), and the discrete variational (DV)-Xalpha molecular orbital (MO) method.
      Both tetraphenylporphyrin (TPP) and tetrakis(p-sulfonatophenyl)porphyrin (TSPP)
      have a single structure: the former has two protonated and two non-protonated N
      atoms in the porphine ring; the latter has four protonated N atoms in the
      porphine ring. In contrast, a combination of XPS, XANES, and DV-Xalpha MO
      calculations shows that tetrakis(p-carboxyphenyl)porphyrin (TCPP) has a dual
      structure: one structure has two protonated and two non-protonated N atoms; the
      other has four protonated N atoms. Furthermore, this result was also considered
      based on the protonation constants of N atoms in the porphyrins. The correlation
      between the strength of electron-withdrawing groups and protonation to N atoms in
      porphyrins can be described using the spectral patterns of the N 1s XPS and N K
      XANES spectra.

PMID- 15984198
TI  - Micelle-sensitized constant-energy synchronous fluorescence spectrometry for the
      simultaneous determination of pyrene, benzo[a]pyrene and perylene.
AB  - The use of micellar media in constant-energy synchronous fluorescence
      spectrometry has been proposed. The influence of some aqueous micellar systems on
      the determination of pyrene, perylene and benzo[a]pyrene has been investigated.
      The presence of these micellar systems allows their determination in aqueous
      media, thus avoiding the use of an organic solvent, and greatly enhances the
      fluorescence signals. The combination of a constant-energy synchronous scanning
      technique and a micellar system provided a single spectrum for the simultaneous
      identification and quantitative determination of the three polycyclic aromatic
      hydrocarbons (PAHs). Further there was no energy transfer among them, making the
      measurement simple and fast. A constant-energy difference of 2800 cm(-1) was
      selected. The analytical characteristics of the proposed method in the presence
      of anionic micelles of sodium dodecylsulfate (SDS) were studied. The detection
      limits were at a level of ng ml(-1). Analysis of water samples from two different
      origins spiked with known amount of pyrene, perylene and benzo[a]pyrene also gave
      satisfactory results, and total average recoveries were greater than 97.1%.

PMID- 15984199
TI  - Determination of cadmium in spring water by graphite-furnace atomic absorption
      spectrometry after coprecipitation with ytterbium hydroxide.
AB  - A coprecipitation method with ytterbium hydroxide was studied for the
      determination of cadmium in water samples by graphite-furnace atomic absorption
      spectrometry. Up to 40 ng of cadmium in water samples was quantitatively
      coprecipitated with ytterbium hydroxide at pH 8.0-11.2. The concentration factor
      was 100 fold. The coprecipitated cadmium was sensitively determined without any
      influence of ytterbium and the calibration curve was linear from 0.1 to 4 ng/mL
      of cadmium. The detection limit (signal/noise = 2) was 2.9 pg/mL in 100 mL of the
      initial sample solution. Twenty-nine diverse ions tested did not interfere with
      the determination in at least a 10000-fold mass ratio to cadmium. The proposed
      method was successfully applied to the determination of cadmium in spring water.

PMID- 15984200
TI  - Preconcentration and determination of trace metals in seawater using a thiol
      cotton fiber minicolumn coupled with inductively coupled plasma mass
      spectrometry.
AB  - A rapid separation and preconcentration method was developed for the
      determination of trace metals Cu, Zn, Cd, and Pb in seawater using a minicolumn
      packed with thiol cotton fiber (TCF) coupled with inductively coupled plasma mass
      spectrometry (ICP-MS). Preconcentration parameters, such as seawater sample
      volume and flow rate and eluent hydrochloric acid concentration, volume and flow
      rate, were optimized. Under the optimized conditions, trace metals Cu, Zn, Cd,
      and Pb in seawater can be determined with no interference from saline matrices.
      When a sample volume of 1500 ml and a sample flow rate of 15 ml min(-1) were
      used, the preconcentration factor of 1500 and RSD value of <7% at ng ml(-1) were
      achieved. The accuracy of the recommended method was verified by the analysis of
      certified reference materials.

PMID- 15984201
TI  - Atomic absorption spectrometry for the automatic indirect determination of
      ascorbic acid based on-the reduction of manganese dioxide.
AB  - A new and simple flow injection method followed by atomic absorption spectrometry
      has been developed for the indirect determination of ascorbic acid. The proposed
      method is based on oxidation of ascorbic acid to dehydroascorbic acid using a
      solid-phase manganese dioxide (30% m/m suspended on silica gel beads) reactor.
      The flow of the sample through the column reduces the MnO2 to Mn(II) in an acidic
      carrier stream of 6.3 mM HNO3 (pH 2.2) with flow rate of 4.0 ml/min at room
      temperature; Mn(II) is measured by atomic absorption spectrometry. The absorbance
      of Mn(II) is proportional to the concentration of ascorbic acid in the sample.
      The calibration curve was linear up to 30 mg/L, with a detection limit of 0.2
      mg/L for a 220 microL injected sample volume. The developed procedure was found
      to be suitable for the determination of AsA in pharmaceuticals and foods with a
      relative standard deviation better than 1.09% and a sampling rate of about 95 h(
      1). The results exhibit no interference from the presence of large amounts of
      organic compounds. The reliability of the method was established by parallel
      determination against the 2,6-dichlorophenol-indophenol methods.

PMID- 15984202
TI  - A simple flow injection spectrophotometric determination of nitrite based on its
      reaction with thiourea.
AB  - A simple flow injection spectrophotometric method for the determination of
      nitrite is described. Nitrite injected into the flow system reacts with thiourea
      in acidic medium and the generated thiocyanate ion reacts with Fe(III) in the
      reagent solution to produce a highly colored product. The influences of chemical
      and physical parameters including reagent concentrations, sample volume injected,
      flow rates of the carrier and reagent solutions, reaction coil length and
      reaction temperature, were studied and optimum values of these parameters were
      established. Under the optimum conditions, the calibration curve for nitrite was
      linear over the concentration range 0.36 - 90 microg ml(-1) without
      preconcentration and over the range 3.8 - 500 ng ml(-1) with a simple online
      preconcentration step using an anion exchange column. The corresponding detection
      limits were 0.36 micro ml(-1) and 3.8 ng ml(-1), respectively. Up to 25 samples
      can be analyzed per hour, with an average relative standard deviation of < or =
      1.2%. Interferences by various foreign ions were studied and the method was
      applied to the determination of nitrite in water and spiked water samples.

PMID- 15984203
TI  - Novel methods for the production of silver microelectrode-arrays: their
      characterisation by atomic force microscopy and application to the electro
      reduction of halothane.
AB  - A new method is proposed for the simple preparation of random silver micro and
      nano-electrode arrays. This employs acoustic streaming directed at a glassy
      carbon surface to "mechanically" attach particles from a suspension of metal
      colloidal or other small particles. The particles tend to adhere to the substrate
      at points of imperfection such as scratches, crevices etc. These arrays are
      compared with arrays formed by the electro-deposition of silver at a glassy
      carbon substrate, with the silver being partially stripped off, leaving a stable
      micro and nanoparticle array on the surface. Both surfaces are characterised
      using optical and atomic force microscopy. The two types of electrodes are
      evaluated to their analytical utility via the electrochemical reduction of
      halothane and their performance compared with that of a silver macroelectrode. A
      notable increase in sensitivity and peak current is observed.

PMID- 15984204
TI  - A potentiometric rhodamine-B based membrane sensor for the selective
      determination of chromium ions in wastewater.
AB  - The construction and performance characteristics of a novel chromate ion
      selective membrane sensor are described and used for determining chromium(III)
      and chromium(VI) ions. The sensor is based on the use of a rhodamine-B chromate
      ion-associate complex as an electroactive material in a poly(vinyl chloride)
      membrane plasticized with o-nitrophenyloctyl ether as a solvent mediator. In a
      phosphate buffer solution of pH 6 - 7, the sensor displays a stable, reproducible
      and linear potential response over the concentration range of 1 x 10(-1) - 5 x
      10(-6) mol l(-1) with an anionic Nernstian slope of 30.8 +/- 0.5 mV decade(-1)
      and a detection limit of 1 x 10(-6) mol l(-1) Cr(VI). High selectivity for Cr(VI)
      is offered over many common anions (e.g., I-, Br-, Cl-, IO4-, CN-, acetate,
      oxalate, citrate, sulfate, phosphate, thiosulfate, selenite, nitrate) and cations
      (e.g., Ag+, Ca2+, Sr2+, Co2+, Ni2+, Cu2+, Mn2+, Fe2+, Zn2+, Cd2+, Al3+, Cr3+).
      The sensor is used for determining Cr(VI) and/or Cr(III) ions in separate or
      mixed solutions after the oxidation of Cr(III) into Cr(VI) with H2O2. As low as
      0.2 microg ml(-1) of chromium is determined with a precision of +/-1.2%. The
      chromium contents of some wastewater samples were accurately assessed, and the
      results agreed fairly well with data obtained by atomic absorption spectrometry.

PMID- 15984205
TI  - Electrochemical studies of derivatized thiol self-assembled monolayers on gold
      electrode in the presence of surfactants.
AB  - Electrochemical impendence spectroscopy (EIS), cyclic voltammetry (CV) and
      differential pulse voltammetry (DPV) were performed to investigate the barrier
      properties and electron transfer of derivatized thiol self-assembled monolayers
      (SAMs) on gold in the presence of surfactants. The thiol derivatives used
      included 2-mercaptoethanesulfonic acid (MES), 2-mercaptoacetic acid (MAA), and N
      acetyl-L-cysteine (NAC). A simple equivalent circuit was derived to fit the
      impedance spectra very well. The negative redox probe [Fe(CN)6](3-/4-) was
      selected to indicate the electron-transfer efficiency on the interface of the
      studied electrodes. It was found that by changing the surface structure of SAMs,
      different surfactants could regulate the barrier properties and electron-transfer
      efficiency in different ways. A positively charged surfactant lowered the
      electrostatic repulsion between the negative redox probe and negatively charged
      surface groups of a monolayer, while enhancing the reversibility of electron
      transfer by virtue of increasing the redox probe concentration within the
      electric double-layer region. A neutral surfactant showed no significant effect,
      while a negative surfactant hindered the access and reaction of redox probe by
      electrostatic repulsion of same-sign charges.

PMID- 15984206
TI  - Electrochemical investigation of 1,3,5-triphenylformazan and its nitro
      derivatives in dimethyl sulfoxide.
AB  - Cyclic voltammetric (CV) and chronoamperometric (CA) behaviors of 1,3,5
      triphenylformazan (TPF), 3-(p-nitrophenyl)-1,5-diphenylformazan (PNF) and 3-(m
      nitrophenyl)-1,5-diphenylformazan (MNF) were studied in dimethyl sulfoxide
      medium. TPF was found to give a single sharp cathodic CV peak corresponding to a
      gain of one-electron per molecule. The diffusion coefficient and the number of
      electrons transferred were calculated using the Baranski equation with the CV
      data obtained by an ultramicroelectrode. Standard rate constants for the
      reduction were calculated by the Klingler-Kochi technique. The electrochemical
      data obtained support the mechanism proposed by Umemoto.

PMID- 15984207
TI  - Electrocatalytic determination of ascorbic acid on a glassy carbon electrode
      chemically modified with cobalt pentacyanonitrosylferrate.
AB  - An electrochemically prepared thin film of cobalt pentacyanonitrosylferrate
      (GC/CoPCNF) was used as a surface modifier for glassy carbon electrodes. The
      oxidation of ascorbic acid on a glassy carbon electrode modified with GC/CoPCNF
      as a working electrode was studied using cyclic voltammetry, rotating disk
      electrode (RDE) voltammetry and chronoamperometry in a 0.25 M KNO3 + 0.25 M
      phosphate buffer (pH 7) solution. The glassy carbon modified with CoPCNF showed
      good electrocatalytic activity toward ascorbic acid oxidation. The kinetics of
      the catalytic reaction was investigated, and the average value of the rate
      constant (k) for the catalytic reaction and the diffusion coefficient (D) were
      evaluated by different approaches for ascorbic acid, and were found to be 3.3 +/-
      0.3 x 10(2) M(-1) s(-1) and 3.2 +/- 0.3 x 10(-6) cm2 s(-1), respectively.

PMID- 15984208
TI  - Development of a narrow-band tunable picosecond dye laser and its application to
      excited-state lifetime measurement of a chlorinated aromatic hydrocarbon.
AB  - The development of a distributed-feedback dye laser, with a pulse width and a
      line width of 25 ps and 8.78 pm, respectively, is described. Using this nearly
      Fourier-transform-limited pulse, we measured the first singlet-excited-state
      lifetime of 1,2,4-trichlorobenzene. The tunable picosecond dye laser developed
      herein has a potential for the lifetime measurement and the efficient multiphoton
      ionization of aromatic hydrocarbons with a larger number of chlorine atoms and
      shorter excited-state lifetimes.

PMID- 15984209
TI  - Determination of bisphenol-A in water by semi-micro column high-performance
      liquid chromatography using 2-methoxy-4-(2-phthalimidinyl)phenylsulfonyl chloride
      as a fluorescent labeling reagent.
AB  - A highly sensitive method for the determination of bisphenol-A in water with semi
      micro column high-performance liquid chromatography using 2-methoxy-4-(2
      phthalimidinyl)phenylsulfonyl chloride as a fluorescent labeling reagent has been
      developed. The labeling reaction was carried out at 70 degrees C for 20 min in
      borate buffer (pH 9.5). The derivative eluted at 11.6 min on a reversed-phase
      column with methanol-water (78:22, v/v) at a flow-rate of 0.2 ml/min. The
      fluorescence was monitored at 308 nm for excitation and 410 nm for emission. The
      detection limit (S/N = 3) was 10 fmol per injection. The labeling yield was about
      95%.

PMID- 15984210
TI  - Determination of peroxidase encapsulated in liposomes using homogentisic acid y
      lactone chemiluminescence.
AB  - Homogentisic acid gamma-lactone (HAL) chemiluminescence (CL) was applied to the
      determination of horseradish peroxidase (HRP) encapsulated in liposomes. HRP was
      detected after the lysis of HRP-trapped liposomes with Triton X-100. CL response
      rate, detection limit and linear range of calibration curve for HRP in HAL CL
      were compared with those in piodophenol (p-IP)-enhanced luminol CL. Maximal light
      emission in HAL CL appeared more rapidly compared to that in p-IP enhanced
      luminol CL, thus resulting in remarkable reduction of CL measurement time. The
      detection limit for HRP in HAL CL was the same as that in p-IP-enhanced luminol
      CL. The linear range of calibration curve for HRP in HAL CL was improved by a
      factor of 50 compared with that in p-IP-enhanced luminol CL. From these results,
      it was found that HAL CL were superior to p-IP-enhanced luminol CL for the
      determination of HRP encapsulated in liposomes.

PMID- 15984211
TI  - Determination of ultratrace amounts of ruthenium(III) by the delayed
      autocatalytic reaction using citric acid.
AB  - A method for determination of ultratrace amounts (ppq levels) of ruthenium(III)
      was developed using a copper(II)-phthalocyanine-3,4',4",4"'-tetrasulfonic sodium
      salt (Cu-PTS) as an indicator in a potassium bromate autocatalytic reaction
      system. A satisfactory calibration curve of ruthenium(III) ion was obtained by
      the time measurement in the concentration range of 1 x 10(-13) M to 5 x 10(-12) M
      with the relative standard deviation (RSD) of 2.8% (n=5). The determination
      limits (3sigma) were 3.30 x 10(-14) M (3.34 ppq).

PMID- 15984212
TI  - Spectrofluorometric determination of trace amounts of coenzyme II using
      norfioxacin-terbium complex as a fluorescent probe.
AB  - When terbium ion (Tb3+)-norfloxacin (NFLX) complex is issued a fluorescent probe,
      in a buffer solution of pH = 7.6, NADP can remarkably enhance the fluorescence
      intensity of the Tb3+ -NFLX complex at lambda = 545 nm. The enhanced fluorescence
      intensity of Tb3+ is in proportion to the concentration of NADP. The dynamic
      range for the determination of NADP is 1.11 x 10(-7) - 6.16 x 10(-5) mol l(-1),
      with a detection limit of 4.31 x 10(-8) mol l(-1). This method is simple,
      practical and relatively free of interference from coexisting substances, so it
      can be successfully applied to determination of NADP in synthetic water samples.

PMID- 15984213
TI  - Method of labeling antibodies with europium(III)-4,7-bis(chlorosulfophenyl)-1,10
      phenanthroline-2,9-di-carboxylic acid chelate.
AB  - On the basis of Eu(III)-4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-di
      carboxylic acid chelate (BCPDA) that was synthesized and characterized for time
      resolved fluoroimmunoassay (TRFIA), Donkey anti-hepatitis B surface (anti-HBs)
      was labeled with BCPDA-Eu3+. Coomassie Brilliant Blue was used to determine the
      protein concentration and radio immunoassay (RIA) for detecting the biological
      activity in the labeled protein. Optimal conditions for the protein labeling were
      obtained by monitoring the reaction. Results suggested that the protein could be
      labeled with BCPDA under relatively moderate conditions. As a practical
      application, a protein-BCPDA-Eu3+ chelate was obtained by using BCPDA-protein
      that reacted with EuCl3 under certain conditions. Some properties of BCPDA and
      protein-BCPDA-Eu3+, such as absorption spectrum, emission spectrum and
      fluorescence lifetime, were discussed. The detection limit and the linear working
      range of the established method were also investigated.

PMID- 15984214
TI  - p-tert-Butylcalix[4]arene-1,3-bis(allyloxyethoxy)ether coated capillaries for
      open-tubular electrochromatography.
AB  - The preparation and characterization of p-tert-butylcalix[4]arene-1,3
      bis(allyloxyethoxy)ether (CA[4]-BAE) chemically coated capillaries via a free
      radical reaction with vinyltriethoxysilane (VTES) that was attached onto the
      inner wall previously were carried out. IR spectra and decreased electroosmotic
      flow (EOF) suggested that the capillary was successfully coated with CA[4]-BAE. A
      slight slope of EOF versus pH at 5 < pH < 9 would help to make the separation
      reproducible. The CA[4]-BAE-coated capillary showed improved separations of
      toluidine isomers, naphthol isomers and polycyclic aromatic hydrocarbons (PAHs)
      compared with an uncoated capillary. The special selectivity indicates that there
      is a certain extent of host-guest interactions between the solutes and the CA[4]
      BAE coating.

PMID- 15984215
TI  - Determination of sulfur compounds in hydrotreated transformer base oil by
      potentiometric titration.
AB  - A method was developed to analyze the distribution of sulfur compounds in model
      sulfur compounds by potentiometric titration, and applied to analyze hydrotreated
      transformer base oil. Model thioethers were oxidized to corresponding sulfoxides
      by tetrabutylammonium periodate and sodium metaperiodate, respectively, and the
      sulfoxides were titrated by perchloric acid titrant in acetic anhydride. The
      contents of aliphatic thioethers and total thioethers were then determined from
      that of sulfoxides in solution. The method was applied to determine the organic
      sulfur compounds in hydrotreated transformer base oil.

PMID- 15984216
TI  - Improving the research base of complementary and alternative medicine.

PMID- 15984217
TI  - Regulation of CAM practitioners: reflecting on the last 10 years.
AB  - This article traces the regulatory developments in CAM in the U.K. over the last
      ten years. CAM's regulatory position is analysed in the broader context of
      regulation across health and social care, including notable regulatory failures
      and the Government's plans for modernisation of healthcare regulation. Future
      regulatory developments are discussed, including the creation of a new CAM
      Council and its possible remit'.

PMID- 15984218
TI  - A century of CAM in New Zealand: a struggle for recognition.
AB  - This paper highlights the emergence of complementary and alternative medicine
      (CAM) within New Zealand. The historical path of development and acceptance of
      CAM from 1908 will be outlined, with reference to the development of current
      legislation and government policy. Emphasis will be placed on rapid changes
      occurring over the last decade. Acupuncture, osteopathy, chiropractics and
      therapeutic massage are presented as examples of CAM development and practice
      within New Zealand. Appendix A represents those modalities currently practiced in
      New Zealand.

PMID- 15984219
TI  - CAM research in Britain: the last 10 years.
AB  - Research into complementary and alternative medicine (CAM) is not as new as it
      might appear from a U.K. perspective. Most continental European countries have a
      long tradition in CAM research. Many studies of homoeopathy, for instance, were
      published decades ago in languages other than English [The trials of homeopathy.
      Origins, structure and development. Stiftung: Essen, Karl und Veronica Carstens,
      2004]. However, it is probably true to say that, in the English speaking world
      and particularly in the U.K., CAM has become a respectable area of scientific
      investigation only during the last decade. In this article, we review the 10
      years of CAM research in Britain.

PMID- 15984220
TI  - CAM in Canada: places, practices, research.
AB  - This paper reflects on the practice and research of complementary and alternative
      medicine (CAM) in Canada. Although certain trends in use, as well as the
      regulation and integration of CAM, are mirrored in many other developed
      countries, some are highlighted as uniquely Canadian with distinct political and
      economic geographies. Similarly, although like in other countries the research of
      CAM is growing rapidly, Canadian scholars have been particularly productive in
      terms of providing unique disciplinary perspectives and the ways in which they
      have organized their research training and collaborations. CAM is clearly not a
      fully integrated and researched option in Canadian health care, yet Canada
      exhibits the foundations for an integrated CAM practice, supported by a growing,
      wide-ranging and well-articulated research evidence-base.

PMID- 15984221
TI  - Complementary and alternative medicine in Australia: a contemporary overview.
AB  - Complementary and alternative medicine (CAM) is a thriving sector in Australian
      health care although it remains largely disconnected from the health mainstream.
      This article looks at the recent history of CAM in Australia with a particular
      focus on regulation, education and representation by professional associations.
      Social forces are coercing the two health systems into relationship but this is
      occurring in an ad hoc and uncoordinated manner as institutions and professions
      respond to consumer needs for integration.

PMID- 15984222
TI  - A reflective overview of complementary therapies for children 1995-2005.
AB  - This article considers briefly how and why complementary and alternative medicine
      has developed in children's care during the last 10 years. Some of the therapies
      utilised by children are discussed, similarities and differences to trends in CAM
      for adults highlighted and a potential role for CAM in children's care in the
      future, suggested.

PMID- 15984223
TI  - Dwelling with Alison: a reflection on expertise.
AB  - Reflection is always purposeful toward realising expert practice. Yet how might
      expertise be recognised? Using a narrative approach, Benner, Tanner and Chesta
      (Expertise in nursing practice. Springer Publishing, New York, 1996) explicated a
      model of expertise that offers the practitioner a useful framework to reflect on
      their expertise which I do using my own narrative of dwelling with Alison, given
      that expert practice must be the concern of every practitioner.

PMID- 15984224
TI  - CAM and cancer care: champions for integration.
AB  - The paper reviews challenges and developments in the integration of complementary
      therapies in cancer care. These issues are examined by reflecting on papers
      published in CTNM in the last 10 years by champions of CAM in cancer care. Given
      the aim of the journal to encourage an inclusive readership, multidisciplinary
      and user perspectives are included. The paper argues for better information,
      improved service provision and CAM choices in public healthcare, leadership
      support, funded research and audit, and user and non-users views.

PMID- 15984225
TI  - Complementary therapies in maternity care: personal reflections on the last
      decade.

PMID- 15984226
TI  - Content analysis of holistic ethics.
AB  - Although biomedical ethical principles are appropriate to evaluate the practice
      of conventional or Western medicine, they may not be appropriate to evaluate the
      practice of complementary therapies (CTs) because the world view of CTs has
      different goats than those of Western medicine. This qualitative research study
      examined the suggestions of 11 practicing RNs from across the United States as to
      what principles should be included in a list of holistic ethical principles. Six
      themes were extracted from the data, which include safety, scope of practice,
      cultural diversity, access, collaboration, and spirituality. To validate their
      utility, the identified set of holistic ethical principles where applied to case
      studies of holistic ethical dilemmas that involving specific CTs. The authors
      suggest that the set of six holistic ethical principles could be used to evaluate
      the virtues and potential infractions of the use of CTs.

PMID- 15984227
TI  - The physiological basis of reflexology and its use as a potential diagnostic
      tool.
AB  - Ill-health changes the anatomy and physiology of affected organs, some of which
      can be observed visually, elicited through physical examination or confirmed
      through biomedical analysis. Understanding how anatomical changes contribute to
      physiological signs and symptoms will help practitioners identify the pathology,
      appreciate its origin and development and justify prescribed interventions in a
      way which can be upheld by critical external scrutiny. Reflexology contributes to
      an holistic approach to care and has recently improved its credibility as a
      discipline which supports orthodox care. Several research publications have
      identified possible theories and principles for the mechanism of action of
      reflexology, but more research to explain its contribution in identifying ill
      health and diseases, as well as appropriate treatment modalities, is needed. This
      paper explores the physiological basis of reflexology, some of the theories for
      the mechanism of action and its potential as a diagnostic tool.

PMID- 15984228
TI  - Report by W. Maddox-Jennings in CTNM 10 (1).

PMID- 15984229
TI  - Formation of spindlelike aggregates and flowerlike arrays of polystyrene-b
      poly(acrylic acid) micelles.
AB  - In this letter we describe a simple physical method for the ordered aggregation
      of scattered single spherical polystyrene-b-poly(acrylic acid) (PS-b-PAA)
      micelles. First, narrow dispersed spindlelike aggregates, about 60 nm in diameter
      and 1.5 microm in length, are obtained from the aggregation of single spherical
      PS-b-PAA micelles at 0 degrees C on a glass slide. Then, the yielding spindlelike
      units can further aggregate into long-ranged, close-packed, flowerlike arrays
      after a given amount of freeze-thaw cycles. The formation of the interesting
      arrays is ascribed to the templated aggregation of micelles on the water
      polycrystal at the freezing point.

PMID- 15984230
TI  - Synthesis of nanostructured metal-organic films: surface X-ray radiolysis of
      silver ions using a langmuir monolayer as a template.
AB  - An application of the radiolysis method using an X-ray synchrotron beam is
      developed as a novel approach to the synthesis of metal-organic films with
      controlled shapes and thickness. We demonstrate that a Langmuir monolayer
      deposited onto a silver ion containing subphase, irradiated by an incident beam
      impinging below the critical angle for total reflection, induces the synthesis of
      a stable nanostructured silver-organic ultrathin film at the air-water interface.
      The X-ray scattering is also used to monitor in situ the structure of the silver
      layer during the synthesis process. The layer is observed by atomic force
      microscopy after its transfer onto a silicon substrate. One observes a film
      thickness of 4.6 nm, in good agreement with the X-ray penetration depth, about
      4.5 nm. The silver structure is oriented by the initial organic film phase. This
      experiment demonstrates the considerable potential of this approach to produce
      various controlled metal-organic films with a surfactant self-assembly as a
      template.

PMID- 15984231
TI  - Morphology control in self-assembled monolayers written by dip pen
      nanolithography.
AB  - Here, we describe the effect of writing speed in dip pen nanolithography on the
      morphology (height and density) of self-assembled monolayers of alkanethiols on
      gold surfaces. The analysis of atomic force microscopy images of written
      monolayers shows that molecules assemble according to a nucleation and growth
      mechanism. Slow writing speeds lead to dense monolayers that can be used either
      to direct the self-assembly of metal nanoparticles or as masks for selective
      etching of conductive gold nanowires.

PMID- 15984232
TI  - Design of extended surface-supported chiral metal-organic arrays comprising
      mononuclear iron centers.
AB  - A design strategy for fabricating a surface-supported chiral metal-organic system
      comprising a regular arrangement of mononuclear iron centers and nanocavities is
      presented. By sequential deposition of 1,2,4-benzenetricarboxylic acid (tmla)
      molecules and iron atoms on a Cu(100) surface under ultrahigh vacuum conditions,
      chiral square-planar Fe(tmla)4 metal-organic complexes are generated, which order
      in extended homochiral arrays. Structure formation and envisioned functionality
      of such metal-organic architectures are discussed.

PMID- 15984233
TI  - Rapid soft lithography by bottom-up enhanced capillarity.
AB  - The growing demand for new solutions to pursue the trend of micro- and
      nanoelectronics predicted by Moore's law is stimulating the development of new
      high-resolution, low-cost lithographies. Here we demonstrate that several bottom
      up approaches can be used to increase the throughput of soft lithography by
      exploiting the enhanced hydrophilicity, the low viscosity, and the fragility of
      the employed materials. In particular, the customized functionalization of the
      involved surfaces to improve the wettability to polymer fluids and the dramatic
      decrease of the viscosity of polymer compounds as the temperature is increased,
      together with the good thermal stability of the functionalized surfaces, allow a
      faster filling of elastomeric channels, up to almost an order of magnitude with
      respect to conventional microfluidics.

PMID- 15984234
TI  - Connect the drops: using solids as adhesives for liquids.
AB  - Colloidal particles are shown to be capable of developing adhesion between liquid
      phases through a bridging mechanism by which intervening, micrometer-scaled,
      fluid films are stabilized. Particle dynamics leading to the assembly of the
      stabilizing structure are discussed. Models for the resulting adhesive force are
      developed from considerations of both interface shape perturbation and the force
      applied by surface tension on an individual particle. Finally, predictions from
      these models are compared to direct measurements of the forces that arise during
      the separation of adhering interfaces. Such comparisons lead to a novel method
      for determining the three-phase contact angle inherent to particles residing at
      fluid interfaces.

PMID- 15984235
TI  - Morphological change of the micelle of poly(styrene)-b-poly(2-vinylpyridine)-b
      poly(ethylene oxide) induced by binding of sodium dodecyl sulfate.
AB  - Morphological change of a micelle of poly(styrene)-b-poly(2-vinylpyridine)-b
      poly(ethylene oxide) (PS-PVP-PEO) polymer was induced by binding sodium dodecyl
      sulfate (SDS) to the PVP block in acidic aqueous solutions. The change in the
      size of SDS/PS-PVP-PEO complexes was detected by dynamic light scattering
      measurements and atomic force microscopy, and the binding of SDS was confirmed by
      zeta-potential measurements. When the micelle was free from SDS in acidic aqueous
      solutions, the hydrodynamic diameter of the micelle was 216 nm, reflecting the
      extended conformation of the PVP block due to the repulsion between protonated
      pyridine units. As the cationic PVP block was electrically neutralized with
      anionic SDS, the diameter was gradually reduced concomitant with the decrease in
      zeta-potential and finally reached 175 nm when the PVP block was completely
      neutralized. The decrease in the diameter shows the morphological change of the
      PVP block from extended to shrunken forms. Further addition of SDS did not cause
      the changes of the diameter nor zeta-potential. This indicates that SDS was not
      bound to the PS-PVP-PEO polymer after the PVP block was fully neutralized and
      that the hydrophobic binding of SDS to the polymer was negligible due to the low
      concentration of SDS.

PMID- 15984236
TI  - Surface plasmon sensor based on the enhanced light transmission through arrays of
      nanoholes in gold films.
AB  - Arrays of nanoholes in a gold film were used to monitor the binding of organic
      and biological molecules to the metallic surface. This technique is particularly
      sensitive to surface binding events because it is based upon the resonant surface
      plasmon enhanced transmission through the array of nanoholes. The sensitivity was
      found to be 400 nm per refractive index unit, which is comparable to other
      grating-based surface plasmon resonance (SPR) devices. The array of nanoholes is
      well suited for dense integration in a sensor chip. Furthermore, the optical
      geometry is collinear, which simplifies the alignment with respect to the
      traditional Kretschmann (reflection) arrangement for SPR sensing.

PMID- 15984237
TI  - Micro-Raman investigations of myelins in aerosol-OT/water system.
AB  - Surfactant outgrowth during dissolution as myelin figures, which happens on
      contact with water, is of prime importance in emulsification and detergency.
      Micro-Raman investigation of different lyotropic phases formed during dissolution
      of aerosol-OT (bis 2-ethylhexyl sulfosuccinate) in water during myelin formation
      reveals the flexible arrangement of the surfactant bilayers in myelin. The
      conformation around CC-CS bond and the hydrocarbon chains of aerosol-OT in the
      different liquid crystalline phases were identified from the fingerprints of CC
      CS stretching, C-C stretching, C-H bending, and stretching frequencies. Existence
      of mixture of trans and gauche conformations around CC-CS bond and that of the
      hydrocarbon chains in myelin supports the fluid nature of bilayers by which it is
      made. Similar conformations of hydrocarbon chains in lamellar phase and in myelin
      support the concept of myelins being rolled up lamella. The observations are in
      line with the disorderness of the hydrocarbon chains in the bilayers of
      phospholipids that has been reported earlier. From the C-C stretching frequencies
      at the root of myelins, the kinked structure of the hydrocarbon chain is
      identified, and loose packing of molecules which would facilitate water transport
      across membranes is evident.

PMID- 15984238
TI  - Vertical motion of a charged colloidal particle near an AC polarized electrode
      with a nonuniform potential distribution: theory and experimental evidence.
AB  - Electroosmotic flow in the vicinity of a colloidal particle suspended over an
      electrode accounts for observed changes in the average height of the particle
      when the electrode passes alternating current at 100 Hz. The main findings are
      (1) electroosmotic flow provides sufficient force to move the particle and (2) a
      phase shift between the purely electrical force on the particle and the
      particle's motion provides evidence of an E2 force acting on the particle. The
      electroosmotic force in this case arises from the boundary condition applied when
      faradaic reactions occur on the electrode. The presence of a potential-dependent
      electrode reaction moves the likely distribution of electrical current at the
      electrode surface toward uniform current density around the particle. In the
      presence of a particle the uniform current density is associated with a
      nonuniform potential; thus, the electric field around the particle has a nonzero
      radial component along the electrode surface, which interacts with unbalanced
      charge in the diffuse double layer on the electrode to create a flow pattern and
      impose an electroosmotic-flow-based force on the particle. Numerical solutions
      are presented for these additional height-dependent forces on the particle as a
      function of the current distribution on the electrode and for the time-dependent
      probability density of a charged colloidal particle near a planar electrode with
      a nonuniform electrical potential boundary condition. The electrical potential
      distribution on the electrode, combined with a phase difference between the
      electric field in solution and the electrode potential, can account for the
      experimentally observed motion of particles in ac electric fields in the
      frequency range from approximately 10 to 200 Hz.

PMID- 15984239
TI  - Layer by layer self-assembled polyelectrolyte multilayers with embedded
      phospholipid vesicles.
AB  - We describe a method to embed phospholipid vesicles into polyelectrolyte
      multilayers built up by the alternate deposition of polyanions and polycations.
      Before deposition, the vesicles are rigidified by polycation adsorption onto
      their surface avoiding their fusion once deposited on the multilayer surface. The
      vesicles adsorb to form a compact and "hard" monolayer as imaged by atomic force
      microscopy. The thickness of the adsorbed vesicle layer, of the order of 250 nm,
      is very close to the diameter of the vesicles in solution. This work should open
      the route to the buildup of multilayer films containing phospholipid vesicles
      that could act as "reservoirs" for drugs or enzymatic nanoreactors.

PMID- 15984240
TI  - Effect of recognized and unrecognized salt on the self-assembly of new
      thermosensitive metal-chelating surfactants.
AB  - New functional thermoreversible metal complexing surfactants consisting of a
      chelating amino acid residue grafted to the tip of a nonionic surfactant [alkyl
      poly(oxyethylene) CiEj] or in a branched position are studied. Nonionic
      surfactants are thermoreversible and exhibit a clouding phenomenon associated
      with phase separation of micelles. The functional molecules retain both the
      surface-active properties and the characteristic thermoreversible behavior.
      Because of the hydrophilic contribution of the chelating group (acetyl lysine),
      the cloud point and the area at the air-water interface are higher for functional
      surfactants than for nonionic precursors. These new surfactants have efficient
      complexing properties toward metal ions and are more efficient than the mixture
      of the corresponding nonionic surfactant and the acetyl lysine ligand solubilized
      in micelles. This reveals the synergistic effect obtained by the covalent link
      between the two functions. Addition of a bulky group on classical amphiphilic
      structures modifies markedly the packing constraints at the origin ofmicellar
      structures. Small-angle X-ray or neutron scattering results, modeled jointly on
      the absolute scale, demonstrate the influence of unrecognized lithium nitrate
      (LiNO3) as well as specifically recognized uranyl nitrate [UO2(NO3)2] salts on
      micellar structure and phase boundaries. The determination of the micellar shape
      variations induced by a recognized salt, that is, a decrease of the polar
      headgroup, allows the rationalization of uncommon synergistic effects on the
      cloud point variation: increase with lithium nitrate, no decrease in the presence
      of uranyl nitrate, and a very large decrease when these two salts are present
      together.

PMID- 15984241
TI  - Gelation of octadecyltrimethoxysilane at the air/water interface: effect of
      perfluorotetradecanoic acid and divalent cadmium ions.
AB  - The effect of an acidic surfactant, perfluorotetradecanoic acid (PFTDA), on the
      gelation of octadecyltrimethoxysilane (ODTMS) monolayers at the air/water
      interface was investigated using a Langmuir film balance, attenuated total
      reflection (ATR) infrared spectroscopy, and atomic force microscopy (AFM). The
      gelation of ODTMS was greatly accelerated by adding only 2 mol % PFTDA into the
      monolayer; in this case, the hydrolysis of ODTMS was completed within a few
      minutes, whereas otherwise it took 18 h. ATR-IR spectroscopy clearly demonstrated
      that the gelation of a 49:1 ODTMS/PFTDA monolayer proceeded on a pure water
      subphase mainly via hydrolysis followed by condensation. In the presence of
      PFTDA, the local acidity at specific sites is presumed to be very high,
      catalyzing the hydrolysis of ODTMS. The extremely fast rate is attributed not
      only to the lateral diffusion of PFTDA in the mixed monolayer but also to proton
      propagation where the proton(s) involved in the initial hydrolysis are transposed
      rapidly to the nearby methoxy groups for subsequent hydrolysis. The catalytic
      activity of PFTDA can be neutralized, however, simply by the addition of
      multivalent metallic ions such as Cd2+ to form saltlike complexes with PFTDA; the
      rate of 2-D sol-gel processes can thus be easily regulated by a minute amount of
      PFTDA and/or Cd2+ added into the reaction system.

PMID- 15984242
TI  - Rheology of hydrophobically modified polyacrylamide-co-poly(acrylic acid) on
      addition of surfactant and variation of solution pH.
AB  - Constant shear and shear dependent viscosity measurements are reported in aqueous
      systems of co- and terpolymers of acrylamide (AM), N-n-alkylacrylamide (C10, C12,
      and C14 alkyl groups), and acrylic acid (AA) with added anionic surfactant sodium
      dodecyl sulfate (SDS). The results are presented as three-dimensional plots of
      viscosity vs surfactant concentration and pH at constant shear rate or viscosity
      vs shear rate and surfactant concentration at constant pH. For terpolymers
      incorporating AA, a strong viscosity maximum is observed at intermediate pH
      values (pH 4-6) where the AA groups are partially ionized and at SDS
      concentrations close to the critical micelle concentration. At high pH, all AA
      incorporating terpolymer solutions with SDS are strongly shear thinning, but at
      pH 3-4 the systems of terpolymers with SDS are strongly shear thickening at low
      shear, followed by a shear-thinning region at high shear. These results are
      explained in terms of surfactant-mediated network formation with polymer coil
      expansion and hydrogen bonding between partially ionized AA groups as additional
      factors.

PMID- 15984243
TI  - Photoinduced transformation of gamma-HCH in the presence of dissolved organic
      matter and enhanced photoreactive activity of humate-coated alpha-Fe2O3.
AB  - This study examined phototransformation of gamma-hexachlorocyclohexane (gamma
      HCH) in different solutions. The presence of dissolved organic matter (DOM)
      inhibited the phototransformation of gamma-HCH. This phenomenon could be
      correlated to the binding interaction between gamma-HCH and DOM. Alpha-Fe2O3
      promoted the transformation of gamma-HCH. The humate-coated alpha-Fe2O3 revealed
      a slight, however significant, favorable effect compared to the bare one. Fourier
      transform infrared spectroscopy (FTIR) offered the direct evidence that humate
      coated alpha-Fe2O3 could form surface Fe(III)-carboxylate complexes by ligand
      exchange. Additional experiments demonstrated that the photocorrosion of alpha
      Fe2O3 coated by DOM was much more acute than that of the bare one. These combined
      results suggested that the transformation of gamma-HCH on humate-coated alpha
      Fe2O3 is more related to a surface complex and not to a semiconductor-assisted
      photoreaction. In the humate-coated alpha-Fe2O3, absorption of a photon results
      in an excited ligand-to-metal charge-transfer state of the complexes, and a rich
      variety of free radical reactions ensue, which is concurrently accompanied by the
      dissolution of the iron oxide. Such reactions may generate reactive transients
      such as superoxide and hydroxyl radicals, which may be expected to transform
      gamma-HCH.

PMID- 15984244
TI  - Polyaniline nanoparticles prepared in rodlike micelles.
AB  - The effect of aniline hydrochloride (AHC) on the size and shape of sodium dodecyl
      sulfate (SDS) micelles has been investigated by dynamic light scattering. A
      monotonic decrease in the diffusion coefficient of the micelles was observed with
      an increase in AHC at fixed SDS concentration. This was ascribed to prolate
      ellipsoidal growth of the micelles due to decrease of the effective headgroup
      area/molecule by adsorption of AHC on SDS micelles. The length of the micelles
      can be tuned by controlling the ratio of concentrations of AHC to SDS.
      Polymerization of aniline in micelles of different sizes leads to the formation
      of colloidal polyaniline with variable sizes. A direct correlation between size
      ofmicelles and size ofpolyaniline particles was observed. Combination of static
      and dynamic light scattering experiments reveal that the conformations of the
      polymer do not change significantly with size of the colloid.

PMID- 15984245
TI  - Depletion-flocculation in oil-in-water emulsions using fibrillar protein
      assemblies.
AB  - This paper shows that low concentrations of beta-lactoglobulin fibrils can induce
      depletion-flocculation in beta-lactoglobulin-stabilized oil-in-water emulsions.
      The minimum required fibril concentration for flocculation was determined
      experimentally for fibril lengths of about 3 and 0.1 microm. The minimum fibril
      concentration for flocculation is two orders of magnitude higher for the short
      fibrils than for the long ones. These experimental results correspond well with a
      theoretical prediction based on a model of spinodal decomposition. In addition,
      rheological measurements were performed, verifying that flocculation was induced
      by a depletion mechanism. The results of this study show that the minimum
      concentration required for depletion-flocculation can be tuned by varying the
      length of the fibrils.

PMID- 15984246
TI  - In situ synchrotron small-angle X-ray scattering/X-ray diffraction study of the
      formation of SBA-15 mesoporous silica.
AB  - The initial stages of the formation of SBA-15 have been studied by in situ
      SAXS/XRD using synchrotron radiation. Modeling of both the diffuse scattering and
      the X-ray diffraction patterns obtained at different stages of the reaction
      results in a detailed description of the different reaction steps. The first step
      in the formation is the liquid-liquid phase separation of spherical P123-silicate
      hybrid micelles after which nucleation and growth of the 2D hexagonal phase
      occurs. Two-dimensional electron density maps calculated on the basis of the
      intensities of the Bragg reflections suggest that changes in the degree of
      intermicellar condensation are responsible for the time-dependent observations.
      The silica source (alkoxysilanes) may be partially unhydrolyzed long after
      formation of the hexagonal structure, since the kinetics of the mesophase
      evolution is notably slower when TEOS is used as the silica precursor as compared
      to TMOS. The results obtained for SBA-15 are compared with other published data
      on the formation ofSBA-15 and of the smaller pore MCM-41 materials.

PMID- 15984247
TI  - Probing the limits of the Derjaguin approximation with scanning force microscopy.
AB  - We have measured the interaction force between a silicon nitride scanning force
      microscopy (SFM) probe and the basal plane of highly oriented pyrolitic graphite
      as a function of pH and ionic concentration in aqueous solutions. Forces in the
      range +/- 50 pN were reconstructed from measured signals using dynamical analysis
      of the cantilever. We modeled the force-separation data using a flat plate
      electric double-layer interaction and assumed the Derjaguin approximation to
      adapt the flat plate geometry for the SFM probe shape. Measured forces were well
      modeled by the theory at high ionic concentrations (10 and 100 mM), where Debye
      lengths were 3.0 and 0.96 nm, respectively. The theory failed to model forces at
      a lower ionic concentration (1 mM), where the Debye length was 9.6 nm. To
      investigate this, we calibrated the SFM probe geometry using blind reconstruction
      and obtained an apex radius of 7 nm. This value suggested that failure of the
      theory was due to an invalidation of the Derjaguin approximation at long Debye
      lengths, where the characteristic length scale for the interaction was larger
      than the size of the SFM probe. The errors were reduced by replacing the
      Derjaguin approximation with a surface element integration. The result
      experimentally demonstrates the limitations of the Derjaguin approximation for
      predicting interactions of nanoscale colloids.

PMID- 15984248
TI  - Control of the water permeability of polyelectrolyte multilayers by deposition of
      charged paraffin particles.
AB  - We present a new way to protect polyelectrolyte multilayers from water,
      consisting in the adsorption and subsequent fusing of charged wax particles atop
      a multilayer. The formation of the wax layer is demonstrated by different
      techniques such as ellipsometry, contact angle measurements, and atomic force
      microscopy. The diffusion of water in protected and unprotected multilayers is
      studied by in situ neutron reflectometry. Whereas a top layer of wax crystals
      already allows substantial reduction of the diffusion, the fusion of this top
      layer leads to the dominating exclusion of water from the multilayers when dipped
      in water. This method opens up new interesting avenues for polyelectrolyte
      multilayers in practical applications where permeability of water, ions, or
      hydrophilic drugs is an issue.

PMID- 15984249
TI  - A generalized scale of free energy of excess adsorption of solute and absolute
      composition of the interfacial phase.
AB  - Moles of a surfactant (gamma2(1)) absorbed per unit area of the solid-liquid
      interface estimated analytically from the difference of the solute molality in
      the bulk phase before and after adsorption have been quantitatively related to
      the absolute compositions deltan1 and deltan2 of the solvent and solute forming
      the inhomogeneous surface phase in contact with the bulk phase of homogeneous
      composition. By use of isopiestic experiments, negative values of gamma2(1) for
      the adsorption of inorganic salts onto a solid-liquid interface have been
      calculated in the same manner. From the linear plot of gamma2(1) versus the ratio
      of the bulk mole fractions of the solute and solvent, values of deltan1 and
      deltan2 have been evaluated under a limited range of concentrations. For the
      adsorption of the surfactant and the inorganic salt respectively onto the fluid
      interface, gamma2(1) values have been evaluated from the surface tension
      concentration data using the Gibbs adsorption equation. Gamma2(1) based on the
      arbitrary placement of the Gibbs dividing plane near the fluid interface is
      quantitatively related to the composition of the inhomogeneous surface phase.
      Also, the Gibbs equation for multicomponent solutions has been appropriately
      expressed in terms of a suitably derived coefficient m. Integrating the Gibbs
      adsorption equation for a multicomponent system, the standard free energy change,
      deltaG degrees, per unit of surface area as a result of the maximum adsorption
      gamma2(m) of the surfactant at fluid interfaces due to the change of the activity
      alpha2 of the surfactant in the bulk from zero to unity have been calculated. A
      similar procedure has been followed for the calculation of deltaG degrees for the
      surfactant adsorption at solid-liquid interfaces using thermodynamically derived
      equations. deltaG degrees values for surfactant adsorption for all such systems
      are found to be negative. General expressions of deltaG degrees for negative
      adsorption of the salt on fluid and solid-liquid interfaces respectively have
      also been derived on thermodynamic grounds. deltaG degrees for all such systems
      are positive due to the excess spontaneous hydration of the interfacial phase in
      the presence of inorganic salt. Negative and positive values of deltaG degree for
      excess surfactant and salt adsorption respectively have been discussed in light
      of a generalized scale of free energy of adsorption.

PMID- 15984250
TI  - Discrete solvation layering in confined binary liquids.
AB  - The solvation force profiles of squalane/octamethylcyclotetrasiloxane (OMCTS)
      mixtures confined between Si3N4 tips and highly oriented pyrolytic graphite
      (HOPG) and hexadecane/OMCTS confined between alkanethiol-functionalized tips and
      freshly cleaved mica have been measured by atomic force microscopy. Measurements
      on HOPG reveal oscillatory behavior where discrete solvation layers of both
      squalane and OMCTS are observed in a single force curve. The large repulsive
      force of the first solvation layer (squalane) on HOPG indicates that it is
      strongly bound. Oscillatory behavior is also observed for hexadecane/OMCTS on
      mica excepting that the oscillations are found in the attractive regime. The
      OMCTS layers in this case are less ordered with slightly larger (approximately 1
      A) periodicities. These results are in agreement with computer simulations for
      binary liquid mixtures but differ qualitatively from surface force apparatus
      experiments.

PMID- 15984251
TI  - Ultrafine Na-4-mica: uptake of alkali and alkaline earth metal cations by ion
      exchange.
AB  - The cation exchange properties of alkali and alkaline earth metal cations at room
      temperature were investigated on an ultrafine, highly charged Na-4-mica (with the
      ideal mica composition Na4Mg6Al4Si4O20F4.xH2O). Ultrafine mica crystallites of
      200 nm in size led to faster Sr2+ uptake kinetics in comparison to larger mica
      crystallites. The alkali metal ion (K+, Cs+, and Li+) exchange uptake was rapid,
      and complete exchange occurred within 30 min. For the alkaline earth metal ions
      Ba2+, Ca2+, and Mg2+, however, the exchange uptake required lengthy periods from
      3 days to 4 weeks to be completed, similar to its Sr uptake, as previously
      reported. Kinetic models of the modified Freundlich and parabolic diffusion were
      examined for the experimental data on the Ba2+, Ca2+, and Mg2+ uptakes. The
      modified Freundlich model described well the Ba2+ ion uptake kinetics as well as
      that for the Sr2+ ion, while for the Ca2+ and Mg2+ ions the parabolic diffusion
      model showed better fitting. The alkali and alkaline earth ion exchange isotherms
      were also determined in comparison to the Sr2+ exchange isotherm. The
      thermodynamic equilibria for these cations were compared by using Kielland plots
      evaluated from the isotherms.

PMID- 15984252
TI  - Influence of molecular environment on the analysis of phospholipids by time-of
      flight secondary ion mass spectrometry.
AB  - Understanding the influence of molecular environment on phospholipids is
      important in time-of-flight secondary ion mass spectrometry (TOF-SIMS) studies of
      complex systems such as cellular membranes. Varying the molecular environment of
      model membrane Langmuir-Blodgett (LB) films is shown to affect the TOF-SIMS
      signal of the phospholipids in the films. The molecular environment of a LB film
      of dipalmitoylphosphatidylcholine (DPPC) is changed by varying the film density,
      varying the sample substrate, and the addition of cholesterol. An increase in
      film density results in a decrease in the headgroup fragment ion signal at a mass
      to-charge ratio of 184 (phosphocholine). Varying the sample substrate increases
      the secondary ion yield of phosphocholine as does the addition of proton-donating
      molecules such as cholesterol to the DPPC LB film. Switching from a model system
      of DPPC and cholesterol to one of dipalmitoylphosphatidylethanolamine (DPPE) and
      cholesterol demonstrates the ability of cholesterol to also mask the phospholipid
      headgroup ion signal. TOF-SIMS studies of simplistic phospholipid LB model
      membrane systems demonstrate the potential use of these systems in TOF-SIMS
      analysis of cells.

PMID- 15984253
TI  - Photochemical patterning of a self-assembled monolayer of 7-diazomethylcarbonyl
      2,4,9-trithiaadmantane on gold films via Wolff rearrangement.
AB  - Photolithographic attachment of functional organic molecules via ester or amide
      linkages to self-assembled monolayers (SAMs) on gold thin films was achieved by
      employing a novel photoreactive surface anchor, 7-diazomethylcarbonyl-2,4,9
      trithiaadmantane. The photoreactive SAM was prepared by the spontaneous physical
      adsorption of the photoreactive surface anchor onto gold surfaces. The alpha
      diazo ketone moiety of the SAM was found to display the classical Wolff
      rearrangement reactivity to produce a ketene intermediate on the exposed area.
      Organic molecules such as alcohols and amines can thus be attached to the gold
      surfaces selectively by the facile in situ formation of ester or amide linkages.
      The structure and reactivity of the photoreactive surface anchor were
      characterized by real-time FT-IR, fluorescence, and polarization modulation
      infrared reflectance absorption spectroscopy (PM-IRRAS). The Wolff rearrangement
      reactivity of the SAM suggested that a "surface-isolated" carbonylcarbene may be
      generated when the SAM was exposed to 255-nm irradiation.

PMID- 15984254
TI  - Surface structure and chemical switching of thioctic acid adsorbed on Au(111) as
      observed using near-edge X-ray absorption fine structure.
AB  - Thioctic acid (alpha-lipoic acid) is a molecule with a large disulfide-containing
      base, a short alkyl chain with four CH2 units, and a carboxyl termination. Self
      assembled monolayer (SAM) films ofthioctic acid adsorbed on Au(111) have been
      investigated with near-edge X-ray absorption fine structure (NEXAFS) spectroscopy
      and X-ray photoelectron spectroscopy (XPS) to determine film quality, bonding,
      and morphology. Using standard preparation protocols for SAMs, that is,
      dissolving thioctic acid in ethanol and exposing gold to the solution, results in
      poor films. These films are highly disordered, contain a mixture of carboxyl and
      carboxylate terminations, have more than monolayer coverage, and exhibit unbound
      disulfide. Conversely, forming films by dissolving 1 mmol thioctic acid into 5%
      acetic acid in ethanol (as previously reported with carboxyl-terminated
      alkanethiols) forms ordered monolayers with small amounts of unbound sulfur.
      NEXAFS indicates tilted over endgroups with the carboxyl group normal on average
      38 degrees from the surface normal. Slight angle-dependent intensity modulations
      in other features indicate alkyl chains statistically more upright than prostrate
      on the surface. Reflection-absorption Fourier transform infrared (RA-FTIR)
      spectra indicate hydrogen bonding between neighboring molecules. In such well
      formed monolayers, a stark reorientation occurs upon deprotonation of the
      endgroup by rinsing in a KOH solution. The carboxylate plane normal is now about
      66 degrees from sample normal, a much more upright orientation. Data indicate
      this reorientation may also cause a more upright orientation to the alkyl portion
      of the molecules.

PMID- 15984255
TI  - Persistence of metastability after expansion of a supercompressed fluid
      monolayer.
AB  - Fluid monolayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine collapse from an
      air/water interface to form a three-dimensional bulk phase at the equilibrium
      spreading pressure (pie) of approximately 47 mN/m. This phase transition limits
      access to higher surface pressures under equilibrium conditions or during slow
      continuous compressions. We have shown previously that these films avoid collapse
      and become metastable when compressed on a captive bubble to surface pressures
      above 60 mN/m and that the metastability persists during expansion at least to
      pie. Here, we first documented the extent of this persistent metastability. Rates
      of isobaric collapse during expansion of the metastable films were up to 3 orders
      of magnitude slower than those during the initial compression to high surface
      pressures. Recovery of the ability to collapse depended on the surface pressure
      to which the films were expanded and how long they were held there. Films
      reverted after brief exposure to 20 mN/m and after 1 h at 35 mN/m. At pie, films
      remained capable of reaching high surface pressures during slow compressions
      after 65 h, although an increase in compressibility above 55 mN/m suggested
      somewhat increased rates of collapse. We also determined if the films remained
      metastable when they acquired sufficient free area to allow reinsertion of
      collapsed material. Faster isobaric expansion in the presence of more collapsed
      material and with further deviation below pie supported the existence of
      reinsertion. The persistence of metastability to pie shows that films with
      sufficient free area to allow reinsertion remain resistant to collapse.
      Observations that suggest heterogeneous reinsertion, however, argue that free
      area may be distributed heterogeneously and leave open the possibility that
      metastability persists because significant regions retain a restricted free area.

PMID- 15984256
TI  - Ion adsorption at the rutile-water interface: linking molecular and macroscopic
      properties.
AB  - A comprehensive picture of the interface between aqueous solutions and the (110)
      surface of rutile (alpha-TiO2) is being developed by combining molecular-scale
      and macroscopic approaches, including experimental measurements, quantum
      calculations, molecular simulations, and Gouy-Chapman-Stern models. In situ X-ray
      reflectivity and X-ray standing-wave measurements are used to define the atomic
      arrangement of adsorbed ions, the coordination of interfacial water molecules,
      and substrate surface termination and structure. Ab initio calculations and
      molecular dynamics simulations, validated through direct comparison with the X
      ray results, are used to predict ion distributions not measured experimentally.
      Potentiometric titration and ion adsorption results for rutile powders having
      predominant (110) surface expression provide macroscopic constraints of
      electrical double layer (EDL) properties (e.g., proton release) which are
      evaluated by comparison with a three-layer EDL model including surface oxygen
      proton affinities calculated using ab initio bond lengths and partial charges.
      These results allow a direct correlation of the three-dimensional,
      crystallographically controlled arrangements of various species (H2O, Na+, Rb+,
      Ca2+, Sr2+, Zn2+, Y3+, Nd3+) with macroscopic observables (H+ release, metal
      uptake, zeta potential) and thermodynamic/electrostatic constraints. All cations
      are found to be adsorbed as "inner sphere" species bonded directly to surface
      oxygen atoms, while the specific binding geometries and reaction stoichiometries
      are dependent on ionic radius. Ternary surface complexes of sorbed cations with
      electrolyte anions are not observed. Finally, surface oxygen proton affinities
      computed using the MUSIC model are improved by incorporation of ab initio bond
      lengths and hydrogen bonding information derived from MD simulations. This
      multitechnique and multiscale approach demonstrates the compatibility of bond
      valence models of surface oxygen proton affinities and Stern-based models of the
      EDL structure, with the actual molecular interfacial distributions observed
      experimentally, revealing new insight into EDL properties including specific
      binding sites and hydration states of sorbed ions, interfacial solvent properties
      (structure, diffusivity, dielectric constant), surface protonation and
      hydrolysis, and the effect of solution ionic strength.

PMID- 15984257
TI  - Mixed alkanethiol self-assembled monolayers as substrates for microarraying
      applications.
AB  - In current microarraying experiments, data quality is in large part determined by
      the quality of the spots that compose the microarray. Since many microarrays are
      made with contact printing techniques, microarray spot quality is fundamentally
      linked to the surface characteristics of the microarray substrate. In this work,
      surface coatings, consisting of self-assembled monolayers (SAMs) of mixed
      alkanethiol molecules, were used to control the surface properties of the
      microarray substrate. X-ray photoelectron spectroscopy and equilibrium contact
      angle measurements were performed in order to confirm the chemical content and
      wettability of these surface coatings. To test their performance in microarraying
      applications, sample microarrays were printed on these mixed alkanethiol films
      and then characterized with a noncontact visual metrology system and a
      fluorescence scanner. This work demonstrates that utilizing mixed alkanethiol
      SAMs as a surface coating provides spatially homogeneous surface characteristics
      that are reproducible across multiple microarray substrates as well as within a
      substrate. In addition, this paper demonstrates that these films are stable and
      robust as they can maintain their surface characteristics over time. Overall, it
      is demonstrated that SAMs of mixed alkanethiols serve as a useful surface
      coating, which enhances spot and therefore data quality in microarraying
      applications.

PMID- 15984258
TI  - Interactions between nonpolar surfaces coated with the nonionic surfactant
      hexaoxyethylene dodecyl ether C12E6 and the origin of surface charges at the
      air/water interface.
AB  - The interactions between nonpolar surfaces coated with the nonionic surfactant
      hexaoxyethylene dodecyl ether C12E6 were investigated using two techniques and
      three different types of surfaces. As nonpolar surfaces, the air/water interface,
      silanated negatively charged glass, and thiolated uncharged gold surfaces were
      chosen. The interactions between the air/water interfaces were measured with a
      thin film pressure balance in terms of disjoining pressure as a function of film
      thickness. The interactions between the solid/liquid interfaces were determined
      using a bimorph surface force apparatus. The influence of the nature of the
      surface on the interaction forces was investigated at surfactant concentrations
      below and above the cmc. The adsorption of the nonionic surfactant on the
      uncharged thiolated surface does not, as expected, lead to any buildup of a
      surface charge. On the other hand, adsorption of C12E6 on the charged silanated
      glass and the charged air/water interface results in a lowering of the surface
      charge density. The reduction of the surface charge density on the silanated
      glass surfaces is rationalized by changes in the dielectric permittivity around
      the charged silanol groups. The reason for the surface charge observed at the
      air/water interface as well as its decrease with increasing surfactant
      concentration is discussed and a new mechanism for generation of OH- ions at this
      particular interface is proposed.

PMID- 15984259
TI  - Chemical modification of the surface of a sulfonated membrane by formation of a
      sulfonamide bond.
AB  - This paper describes a novel approach for the surface modification of a cation
      exchange membrane, bearing sulfonate groups, by a cationic layer. The
      modification procedure involved the chlorosulfonation of the sulfonate groups of
      the base membrane with thionyl chloride, followed by a reaction with a diamine to
      yield a sulfonamide bond and a terminal amine. The latter could be quaternized by
      reaction with methyl iodide or protonated by soaking in acidic media. The
      membranes were characterized in detail by attenuated total reflectance Fourier
      transform infrared and X-ray photoelectron spectroscopies as well as elemental
      analysis to confirm that the above reactions occurred. The selectivity of these
      membranes toward the electrochemically assisted transport of protons versus Zn2+
      metallic cations was determined during an electrodialysis in a two-compartment
      electrochemical cell. The data indicate a significant decrease of the transport
      of the metallic cations following modification of the membrane with the cationic
      layer. The later allows for the transport of protons from the catholyte to the
      anolyte compartment with much improved selectivity since the divalent cations are
      excluded from the membrane due to the electrostatic barrier of the cationic
      layer.

PMID- 15984260
TI  - Adsorption of organic matter at mineral/water interfaces. 2. Outer-sphere
      adsorption of maleate and implications for dissolution processes.
AB  - The effects of the adsorption of a simple dicarboxylate low molecular weight
      organic anion, maleate, on the dissolution of a model aluminum oxide, corundum
      (alpha-Al2O3), have been examined over a range of different maleate
      concentrations (0.125-5.0 mM) and pH conditions (2-10). In situ attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) spectroscopic measurements
      indicate that maleate binds predominantly as an outer-sphere, fully deprotonated
      complex ([triple bond]AlOH2+ -Mal2-) at the corundum surface over the entire
      range of maleate concentrations and pH conditions investigated. In accordance
      with the ATR-FTIR findings, macroscopic adsorption data can be modeled as a
      function of maleate concentration and pH using an extended constant capacitance
      approach and a single [triple bond]AlOH2+ -Mal2- species. Outer-sphere adsorption
      of maleate is found to significantly reduce the protolytic dissolution rate of
      corundum under acidic conditions (pH < 5). A likely mechanism involves steric
      protection of dissolution-active surface sites, whereby strong outer-sphere
      interactions with maleate hinder attack on those surface sites by dissolution
      promoting species.

PMID- 15984261
TI  - Dielectric properties and frequency response of self-assembled monolayers of
      alkanethiols.
AB  - This paper presents dielectric properties of alkanethiol self-assembled
      monolayers (SAMs) under an ac electric field. Using a Hg-SAM/SAM-Hg junction, we
      measured the ac impedance of alkanethiol SAMs using a sinusoidal perturbation of
      30 mV (peak-to-peak) with frequency ranging from 1 Hz to 1 MHz at zero bias.
      Semicircles at higher frequencies and at middle frequencies along with Warburg
      lines at lower frequencies were observed in complex plane impedance plots, that
      is, Nyquist plots. The frequency response of SAMs was analyzed by modeling the
      junction using an equivalent circuit and fitting the Nyquist plots. The
      semicircles at higher frequencies are attributed to the effect of the SAM/SAM
      interfaces, and the ones at middle frequencies are attributed to the effect of
      alkanethiol SAMs. The comparison in the plots of the imaginary part of the
      impedance Z against frequency for the bare Hg electrodes (in pure ethanal) and
      the SAM-covered Hg electrodes (in alkanethiol solution) supports the analysis.
      The Warburg lines are attributed to a certain ionic impurity. The dielectric loss
      spectra are further analyzed. Chain-length-dependent peaks, which correspond to
      different relaxation mechanisms, at higher frequencies and middle frequencies
      were observed in the spectra of the dissipation factor (tan delta vs frequency).
      The peaks move to small frequency with the increase of chain length of
      alkanethiols. Using a correlation of peak position with the chain length, we then
      derived active energies of 39-99 meV for alkanethiol SAMs of C7-C18 under an ac
      electric field.

PMID- 15984262
TI  - Criteria for ultralyophobic surfaces.
AB  - Very rough surfaces can suspend small liquid drops and produce very large contact
      angles. This behavior often is referred to as ultralyophobicity or super
      repellency. It is proposed that two criteria must be met to invoke
      ultralyophobicity: a contact line density criterion and asperity height
      criterion. The proposed criteria were tested using experimental data available in
      the literature and were found to correctly predict suspension of small water
      drops on model rough surfaces with a wide variety of asperity shapes, sizes, and
      spacing.

PMID- 15984263
TI  - Catalytic activity of myoglobin immobilized on zirconium phosphonates.
AB  - The adsorption and catalytic activity of myoglobin (Mb) on zirconium phosphonates
      (a-zirconium benzenephosphonate (alpha-ZrBP), a-zirconium
      carboxyethanephosphonate (alpha-ZrCEP), and a novel layered zirconium fluoride
      aminooctyl-N,N-bis(methylphosphonate) (ZrC8)) were investigated. The maximum
      adsorption was reached after 16 h of contact and was greater on hydrophobic
      supports such as alpha-ZrBP and ZrC8 compared to hydrophilic supports such as
      alpha-ZrCEP. The equilibrium adsorption isotherms fitted the Langmuir equation,
      suggesting the presence of a monolayer of protein molecules on the support
      surfaces. The catalytic activities of free Mb and of the obtained biocomposites
      were studied in terms of the oxidation of two aromatic substrates, o
      phenylenediamine and 2-methoxyphenol (guaiacol), by hydrogen peroxide. The
      oxidation catalyzed by immobilized myoglobin followed the Michaelis-Menten
      kinetics, similar to oxidation by free Mb. The kinetic parameters, kcat and KM,
      were significantly affected by the adsorption process. Mb/alpha-ZrCEP was the
      most efficient biocatalyst obtained, probably because of the hydrophilic nature
      of the support. The effect of immobilization on the stability of Mb toward
      inactivation by hydrogen peroxide was also investigated, and an increased
      resistance was found. The biocomposites obtained can be stored at 4 degrees C for
      months without a significant loss of catalytic activity.

PMID- 15984264
TI  - Adsorption of poly(ethyleneimine) on silica surfaces: effect of pH on the
      reversibility of adsorption.
AB  - The role of polymer charge density in the kinetics of the adsorption and
      desorption, on silica, of the polyelectrolyte poly(ethyleneimine) (PEI) was
      investigated by stagnation-point flow reflectometry. In the first series of
      experiments, PEI solutions were introduced at the same ionic strength and pH as
      the background solvent. It was found that the adsorbed amount of PEI increased by
      increasing pH. In the second series of investigations, several PEI solutions with
      ascending pH were introduced consecutively into the cell. In these cases, a
      stepwise buildup of the adsorbed amount was observed and the "final" adsorbed
      amounts were observed to be roughly equal with the adsorbed amounts of the first
      series of measurements at the same pH. Finally, adsorption/desorption experiments
      were performed where the preadsorption of PEI was followed by the introduction of
      PEI solutions of descending pH. No desorption was detected when the pH changed
      from pH = 9.7 to pH = 5.8. However, when there was a 9.7 --> 3.3 or 5.8 --> 3.3
      decrease in the pH, the kinetic barriers of desorption seemed to completely
      disappear and roughly the same adsorbed amount as in the first series of
      experiments at pH = 3.3 was quickly attained by desorption of the PEI. This study
      reveals the high impact of pH, affecting parameters such as charge density of the
      surface and polyelectrolyte as well as the structure of the adsorbed
      macromolecules, on the desorption properties of weak polyelectrolytes. The
      observed interfacial behavior of PEI may have some important consequences for the
      stability of alternating polyelectrolyte multilayers containing weak
      polyelectrolytes.

PMID- 15984265
TI  - Role of surface heterogeneity and molecular interactions in the charge-transfer
      process through self-assembled thiolate monolayers on Au(111).
AB  - A comparative study of charge-transfer processes from/to methyl-terminated and
      carboxylate-terminated thiolate-covered Au(111) surfaces to/from immobilized
      methylene blue (MB) molecules is presented. Scanning tunneling microscopy images
      with molecular resolution reveal the presence of molecular-sized defects, missing
      rows, and crystalline domains with different tilts that turn the thickness of the
      alkanethiolate SAM (the spacer) uncertain. The degree of surface heterogeneity at
      the SAMs increases as the number of C units (n) in the hydrocarbon chain
      decreases from n = 6. Defective regions act as preferred paths for MB
      incorporation into the methyl-terminated SAMs, driven by hydrophobic forces. The
      presence of negative-charged terminal groups at the SAMs reduces the number of
      molecules that can be incorporated, immobilizing them at the outer plane of the
      monolayer. Only MB molecules incorporated into the SAMs close to the Au(111)
      surface (at a distance < 0.5 nm) are electrochemically active. MB molecules
      trapped in different defects explain the broad shape and humps observed in the
      voltammogram of the redox couple. The heterogeneous charge-transfer rate
      constants for MB immobilized into methyl-terminated thiolate SAMs are higher than
      those estimated for carboxylate- terminated SAMs, suggesting a different
      orientation of the immobilized molecule in the thiolate environment.

PMID- 15984266
TI  - Electrochemical and atomic force microscopy study of carbon surface modification
      via diazonium reduction in aqueous and acetonitrile solutions.
AB  - Electrochemical reduction of the diazonium salts of 4-nitrobenzene and 4
      nitroazobenzene-4'- has been investigated in aqueous acid and acetonitrile media
      at carbon surfaces. Using pyrolyzed photoresist films as the substrate, we have
      examined the deposited films using electrochemistry and atomic force microscopy
      (AFM). Film thicknesses were measured by scratching through the film with an AFM
      tip. The procedure employed two AFM cantilevers with different lengths, located
      on the one device. When the shorter cantilever engages the surface in tapping
      mode, the longer cantilever (which is not resonating) imbeds into the surface
      with a constant force. For both modifiers and modification media, film
      thicknesses increase with deposition time to a limiting value. With equivalent
      modification conditions, films prepared in aqueous acid medium have lower
      limiting thicknesses than those prepared in acetonitrile. For nitrophenyl (NP)
      films, the same trends are found when calculating surface coverages from the
      charge associated with the reduction of surface -Ar-NO2 groups. Lower limiting
      film thicknesses and surface coverages for films prepared in aqueous conditions
      is attributed to growth of inherently more blocking films and is supported by
      examination of the response of the Fe(CN)6(3-/4-) couple at NP-modified surfaces.
      Combination of voltammetrically determined surface coverage and film thickness
      data yields a surface coverage of -Ar-NO2 groups of (2.5 +/- 0.5) x 10(-10) mol
      cm(-2) for a film thickness equivalent to a monolayer of NP groups.

PMID- 15984267
TI  - Three-dimensional arrangements of polystyrene latex particles with a hyperbolic
      quadruple electrode system.
AB  - An attempt was made to arrange polystyrene latex particles (2, 5, and 10 microm
      in diameter) dispersed in aqueous media making use of their dielectrophoresis and
      electrophoresis with a hyperbolic quadruple electrode system. Application of a
      high-frequency ac field enabled the particles to arrange themselves between the
      electrodes forming a particle monolayer due to the negative dielectrophoretic
      force. Simultaneous application of high-frequency ac and dc fields caused the
      particles to gather in the region surrounded by the electrodes to form particle
      multilayers. Appropriate choice of the way of applying an electric field thus
      allowed the reversible control of particle arrangements (monolayer, multilayer,
      dispersion). Reapplication of an ac field to the particle layers produced highly
      dense particle multilayers.

PMID- 15984268
TI  - Electrostatic interactions between double layers: influence of surface roughness,
      regulation, and chemical heterogeneities.
AB  - Electrostatic interactions between two surfaces as measured by atomic force
      microscopy (AFM) are usually analyzed in terms of DLVO theory. The discrepancies
      often observed between the experimental and theoretical behavior are usually
      ascribed to the occurrence of chemical regulation processes and/or to the
      presence of surface chemical or morphological heterogeneities (roughness). In
      this paper, a two-gradient mean-field lattice analysis is elaborated to
      quantifying double layer interactions between nonplanar surfaces. It allows for
      the implementation of the aforementioned sources of deviation from DLVO
      predictions. Two types of ion-surface interaction ensure the adjustment of
      charges and potentials upon double layer overlap, i.e., specific ionic adsorption
      at the surfaces and/or the presence of charge-determining ions for the surfaces
      considered. Upon double layer overlap, charges and potentials are adjusted via
      reequilibrium of the different ion adsorption processes. Roughness is modeled by
      grafting asperities on supporting planar surfaces, with their respective
      positions, shapes, and chemical properties being assigned at will. Local
      potential and charge distributions are derived by numerically solving the
      nonlinear Poisson-Boltzmann equation under the boundary conditions imposed by the
      surface profiles and regulation mechanism chosen. Finite size of the ions is
      taken into account. A number of characteristic situations are briefly discussed.
      It is shown how the surface irregularities are reflected in the Gibbs energy of
      interaction.

PMID- 15984269
TI  - Infrared reflection absorption spectroscopy of the sulfuric acid anion adsorbed
      on Pd(S)-[n(111) x (111)] electrodes.
AB  - Adsorption of the sulfuric acid anion (HSO4- or SO42-) has been studied on Pd(S)
      [n(111) x (111)] electrodes (n = 2, 3, 5, 9, 20, infinity) using in situ infrared
      reflection absorption spectroscopy (IRAS). A single band is observed around 1200
      cm(-1) on all the electrodes. The band is assigned to the SO stretching vibration
      of the sulfuric acid anion adsorbed with three- or onefold geometry. This result
      differs from the case of Pt-stepped surfaces on which two IRAS bands are observed
      around 1200 and 1100 cm(-1). The maximum coverage of the sulfuric acid anion is
      enhanced with the increase of the terrace width. The surfaces with n more than 3
      have similar IRAS band shifts (dv/dE). Pd-stepped surfaces, for which the terrace
      is wide enough for the anion adsorption, adsorb the anion on the terrace rather
      than the step.

PMID- 15984270
TI  - Mixology of protein solutions and the Vroman effect.
AB  - Mixing rules stipulating both concentration and distribution of proteins adsorbed
      to the liquid-vapor (LV) interphase from multicomponent aqueous solutions are
      derived from a relatively straightforward protein-adsorption model. Accordingly,
      proteins compete for space within an interphase separating bulk-vapor and bulk
      solution phases on a weight, not molar, concentration basis. This results in an
      equilibrium weight-fraction distribution within the interphase that is identical
      to bulk solution. However, the absolute interphase concentration of any
      particular protein adsorbing from an m-component solution is 1/mth that adsorbed
      from a pure, single-component solution of that protein due to competition with m 
      1 constituents. Applied to adsorption from complex biological fluids such as
      blood plasma and serum, mixing rules suggest that there is no energetic reason to
      expect selective adsorption of any particular protein from the mixture. Thus,
      dilute members of the plasma proteome are overwhelmed at the hydrophobic LV
      surface by the 30 classical plasma proteins occupying the first 5 decades of
      physiological concentration. Mixing rules rationalize the experimental
      observations that (i) concentration-dependent liquid-vapor interfacial tension,
      gammalv, of blood plasma and serum (comprised of about 490 different proteins)
      cannot be confidently resolved, even though serum is substantially depleted of
      coagulable proteins (e.g., fibrinogen), and (ii) gammalv of plasma is startlingly
      similar to that of purified protein constituents. Adsorption-kinetics studies of
      human albumin (66.3 kDa) and IgM (1000 kDa) binary mixtures revealed that
      relatively sluggish IgM molecules displace faster-moving albumin molecules
      adsorbing to the LV surface. This Vroman-effect-like process leads to an
      equilibrium gammalv reflecting the linear combination of weight/volume
      concentrations at the surface predicted by theory. Thus, the Vroman effect is
      interpreted as a natural outcome of protein reorganization to achieve an
      equilibrium interphase composition dictated by a firm set of mixing rules.

PMID- 15984271
TI  - Hierarchical networks of casein proteins: an elasticity study based on atomic
      force microscopy.
AB  - 2D- and 3D-atomic force microscopy (AFM) experiments were performed on single
      casein micelles (CM) in native state, submerged in liquid, using a home-built AFM
      instrument. The micelles were immobilized via carbodiimide chemistry to a self
      assembled monolayer supported on gold-coated slides. Off-line data analysis
      allowed the extraction of both surface topography and elastic properties.
      Relative Young moduli (E*) were derived from force-vs-indentation curves, using
      the Hertz theory. The obtained E* values were found to increase with CM diameter,
      following a straight line dependence. The data showed that temperature, via its
      influence on both the protein-protein interactions and the composition of the
      micelle, has a clear effect on the mechanical properties of the CMs: higher
      temperatures and lower serum casein concentrations result in stiffer micelles.
      For pH < or = 5.6, effecting calcium phosphate release from the micelles by
      decreasing the pH does not have a large effect on CM stiffness. On decrease of
      the pH below 5.0, particulate gels and multilayers were obtained. Their measured
      elasticity (expressed by an equivalent G'AFM) agrees remarkably well with the
      storage moduli as measured with a conventional rheometer. Compared to single
      micelles, gels from nonheated CM suspensions are about 3 orders of magnitude
      softer. The "softness" of these gels (measured under compression or shear)
      therefore must come from the microscopic and/or mesoscopic links rather than the
      micelles themselves.

PMID- 15984272
TI  - Hierarchical assembly and compliance of aligned nanoscale polymer cylinders in
      confinement.
AB  - We report a combined top-down/bottom-up hierarchical approach to fabricate
      massively parallel arrays of aligned nanoscale domains by means of the self
      assembly of asymmetric polystyrene-block-poly(ethylene-alt-propylene) diblock
      copolymers. Silicon nitride grating substrates of various depths and
      periodicities are used to template the alignment of the high-aspect-ratio
      cylindrical polymer domains. Alignment is nucleated by polystyrene preferentially
      wetting the trough sidewalls and is thermally extended throughout the polymer
      film by defect annihilation. Topics discussed include a detailed analysis of the
      capacity of this system to accommodate lithographic defects and observations of
      alignment beyond the confined channel volumes. This graphoepitaxial methodology
      can be exploited in hybrid hard/soft condensed matter systems for a variety of
      applications.

PMID- 15984273
TI  - Sensitization of nanostructured TiO2 by electrostatic coupling of ionic dyes to
      ionic absorbates.
AB  - It is shown that an ionic dye Y can be electrostatically bonded to an ionic
      molecule X of opposite charge anchored to a TiO2 surface via suitable ligands.
      Dye-sensitized solid-state photovoltaic cells of the configuration n-TiO2/X-Y/p
      CuSCN were constructed with X = trihydroxybenzoic acid or mercurochrome and Y =
      methyl violet. Cells of this configuration were found to be more efficient and
      delivered higher short-circuit photocurrents and open-circuit photovoltages
      compared to the cells based only on methyl violet or mercurochrome. It is
      suggested that this technique would be a means of extending the spectral response
      of dye-sensitized photovoltaic devices. The formation of a wider barrier by
      coupling of anionic and cationic species also improves the cell performance by
      suppression of recombination.

PMID- 15984274
TI  - A porous silicon-palladium composite film for optical interferometric sensing of
      hydrogen.
AB  - Porous Si Fabry-Perot films are coated with Pd via immersion plating. The
      materials are characterized by electron microscopy and infrared spectroscopy. The
      Pd-coated porous Si samples exhibit distinct Fabry-Perot fringes in the optical
      reflection spectrum due to thin film optical interference in the porous Si layer,
      though the reflectivity spectrum loses fidelity upon Pd coating. The effect of H2
      exposure on the interference spectrum is studied. Absorption of hydrogen into Pd
      induces a lattice expansion, which results in a shift of the optical fringes and
      a decrease in the reflected intensity. The detection limit measured at room
      temperature is approximately 0.2% (by volume) in an N2 carrier gas, with a
      response time of a few seconds.

PMID- 15984275
TI  - Parametric study on electrochemical deposition of copper nanoparticles on an
      ultrathin polypyrrole film deposited on a gold film electrode.
AB  - Monoshaped and monosized copper nanostructured particles have been prepared by
      potentiostatic electrochemical deposition on an ultrathin polypyrrole (PPY) film,
      electrochemically grown on a Si(100) substrate sputter-coated with a thin gold
      film or gold-film electrode (GFE). The crystal size and the number density of the
      copper nanocrystals have been examined by varying several deposition parameters,
      including the thickness of the gold film, the PPY film thickness, the applied
      potential, and the Cu2+ and the electrolyte concentrations for copper deposition.
      Optimal conditions for uniform growth ofnanocrystals well-dispersed on the GFE
      have been determined, along with insight into the mechanism of crystal growth. A
      minimum gold film thickness of 80 nm is required to eliminate the effects of the
      gold-silicon interface. The PPY film thickness and homogeneity principally affect
      the shape uniformity of the nanocrystals, while the copper deposition potential
      could be used to regulate the size and number density of the nanocrystals. Both
      the Cu2+ and electrolyte concentrations are also found to play important roles in
      controlling the electrodeposition of nanocrystal growth.

PMID- 15984276
TI  - Epitaxial chemical deposition of ZnO nanocolumns from NaOH solutions.
AB  - A new method of depositing expitaxial ZnO nanocolumns on sputter-coated ZnO
      substrates is described that utilizes supersaturated zincate species in sodium
      hydroxide solutions and requires no complexing agents. Uniform arrays of columns
      are grown reproducibly over entire substrates in 10-50 min. Columns are 50-2000
      nm long and 50-100 nm wide. Strict substrate cleaning and/or preparation was not
      necessary with this method, in contrast to many other techniques, probably
      because the high pH generates a reproducible surface. The interfacial properties
      of the substrate are critical to lowering the activation energy for columnar
      growth; therefore films grow only on substrates precoated with ZnO, not on bare
      glass or ITO- or SnO2-coated glass. Factors affecting the column growth are
      elucidated, and experimental observations are correlated with crystal growth
      theory.

PMID- 15984277
TI  - Inkjet deposition of alkanethiolate monolayers and DNA oligonucleotides on gold:
      evaluation of spot uniformity by wet etching.
AB  - Inkjet printing allows localized, contact-free deposition of liquids onto
      arbitrary substrates. In this article we demonstrate the fast formation of high
      quality self-assembled monolayers (SAMs) on gold surfaces. Using a selective etch
      process, we verify the uniformity of the deposited spots. A direct comparison
      with microcontact-printed SAMs on Au revealed similar resist quality as inkjet
      deposited alkanethiolate SAMs. Likewise, inkjet printing of thiol-functionalized
      and non-thiolated single-stranded DNA oligomers formed molecular layers
      protecting Au from etchants. For all compounds used, we achieved etched patterns
      that were homogeneous and free of defects. These results indicate that an inkjet
      is a convenient tool for surface functionalization and the direct writing of
      molecular films and resists.

PMID- 15984278
TI  - Simulation of phase equilibria in lamellar surfactant systems.
AB  - The coexistence of two lamellar liquid crystalline phases has been investigated
      by means of Monte Carlo simulations. The surfaces of the negatively charged
      bilayers formed by the surfactant molecules are modeled as planar infinite walls
      with a uniform surface charge density. Water is treated as a dielectric
      continuum, and only electrostatic interactions are considered. The counterions
      are mono- and divalent point ions, and their ratio is allowed to vary. Monovalent
      counterions lead to a repulsive osmotic pressure at all separations, while an
      attractive region exists when the counterions are divalent. In the latter case,
      one would expect a phase separation to take place, although it is not observed
      experimentally due to the limited stability of the lamellar phase at high water
      content. In a system with mixed counterions, however, the osmotic pressure
      exhibits a van der Waals loop under such conditions that two phases can coexist.
      A phase diagram is constructed, and the agreement with experimental data is
      excellent.

PMID- 15984279
TI  - Computer simulation studies of Newton black films.
AB  - We study via molecular dynamics simulations thin films (Newton black films, NBF)
      consisting of water coated with sodium dodecyl sulfate (SDS) surfactants. We
      analyze in detail the film properties (distribution of particles, pair
      correlation functions, roughness of the film, tilt angle of the hydrocarbon
      chain, electron density profiles, and mobility of water molecules) as a function
      of water content in the film core (i.e., film thickness, H). Our simulations
      indicate that water is part of the bilayer structure as solvation water. We
      estimate that around 2.25 water molecules per surfactant are part of this
      solvation structure. The structural analysis of the NBF shows that the headgroups
      exhibit a high degree of in-plane ordering. We find evidence for the existence of
      cavities in the monolayer, where only water is present. The basic structure of
      the monolayer is conserved down to water contents of the order of 4 water
      molecules per surfactant (H approximately equal to 11 A). The computed monolayer
      roughness for the present model is 2.5 A, in good agreement with the experimental
      data. We find that the roughness is very sensitive to the details of the
      interatomic potentials. Water mobility calculations emphasize the sluggish
      dynamics of very thin NBF. Diffusion coefficients of water in the lateral
      direction strongly decrease with film thickness. We find that the typical mean
      squared displacement of water in the direction normal to the bilayer is between 9
      and 80 A2. Overall, our results indicate that the equilibrium SDS Newton black
      films studied in the X-ray experiments contain from 2 to 4 water molecules per
      surfactant.

PMID- 15984280
TI  - Mechanical instability induced by the desiccation of sessile drops.

PMID- 15984281
TI  - Gravitational, vertical compression of colloidal crystals as studied by the
      Kossel diffraction method.

PMID- 15984282
TI  - Formation and characterization of water-soluble platinum nanoparticles using a
      unique approach based on the hydrosilylation reaction.

PMID- 15984283
TI  - Dispersions of individual single-walled carbon nanotubes of high length.
AB  - In summary, we have presented a suitable approach to obtain surfactant-stabilized
      suspensions of long, individually dispersed SWCNTs essentially free of bundles.
      The combination of mild tip and bath ultrasonication has proven effective in
      unbundling the SWCNT ropes and, at the same time, in minimizing tube shortening.
      This method is expected to be useful for applications that critically depend on
      the availability of bulk dispersions of long, individual tubes with minimized
      defect densities, such as for nanotube-based electronics and composite materials.
      Furthermore, the observed purification-induced changes in the electronic
      structure of HiPco SWCNTs indicate that care has to be taken when comparing their
      properties with those of the as-produced material.

PMID- 15984284
TI  - [Cecile Lambert. Recipient of the 2004 Insignia of Merit. Interview by Nataly
      Rainville].

PMID- 15984285
TI  - [Establishment of the mother-infant and father-infant relationship in the
      perinatal period].
AB  - This qualitative and longitudinal study aims at defining a model of early parent
      infant relationships in the perinatal period. Eighteen parental couples were
      interviewed. The resulting model is based on five themes in the parent-infant
      relationship, i.e. discovery of the infant, physical proximity, emotional
      closeness, initiation of complementary interactions and personal commitment to
      the parental role. The article clearly shows the differences between mothers' and
      fathers' experiences in developing these relationships with their infant. The
      nurse's assessment of early parent-infant relationships and her interventions are
      discussed in a second article, p. 32.

PMID- 15984286
TI  - [Towards interprofessional collaboration].

PMID- 15984287
TI  - [Parent-child relationship in the perinatal period: evaluation and intervention].

PMID- 15984288
TI  - [It is possible to prevent medication errors!].

PMID- 15984289
TI  - [Being in compliance, a divided pride].

PMID- 15984290
TI  - [Fields, objectives and methodology of the consensus conference entitled
      "Management of atopic dermatitis in children"].

PMID- 15984291
TI  - [Management of atopic dermatitis in children. Recommendations text].

PMID- 15984292
TI  - [Atopic dermatitis: definition, epidemiology, natural history, severity and
      scores].
AB  - This paper is aimed at defining atopic dermatitis (AD) in a pragmatic and
      historical perspective (diagnostic criteria, severity scores, quality of life
      scales) and to summarise its natural history, complications included. The
      signification of atopy is still not clearly defined. Immuno-allergologists tend
      to limit the term to a hereditary predisposition of the immune system. The
      definition of atopic dermatitis in infants has not been validated. Atopic
      dermatitis in France has a prevalence of 2 to 5 p. 100 at any age (6 to 9 p. 100
      before the age of 15), depending on the strictness of the criteria applied. For
      infants suffering from AD with a first degree parent exhibiting AD, asthma or
      rhinitis, the risk of developing asthma is of around 40 p. 100. This data
      suggests the interest of preventive measures targeting the skin in the hypothesis
      of an atopic "march". There is no consensus to define the terms used in the
      description of the maintenance phase of treatment of this chronic and recurring
      affection. Proposals have been made to define the terms of flares, remission,
      intolerance and resistance.

PMID- 15984293
TI  - [Pathogenesis of atopic dermatitis].
AB  - Atopic dermatitis (AD) is a chronic inflammatory dermatosis due to the activation
      ofT-cell lymphocytes specific to protein antigens in the skin. The AD antigens
      come from molecules in the environment (extrinsic AD allergens associated with
      hyper IgE levels) or from self antigens (intrinsic AD autoantigens). The
      physiopathology of AD implies dendritic cells, specific T-cell lymphocytes, a
      network of type 1 and 2 cytokines and inflammatory chemokines. Extrinsic AD is
      the best known because of the existence of animal models and skin tests with
      allergens in humans (atopy patch tests), which reproduce eczema lesions. Although
      the role of the penetration of pneumo-allergens, prompted by abnormalities in the
      skin barrier, in inducing AD flares is established, recent works suggest that
      other types of allergens (trophallergens) and/or proteins derived from micro
      organisms may be responsible in some patients. The ongoing studies on animal
      models of AD will no doubt permit rapid progression in our knowledge of the
      mechanisms involved in the origin of the disease and the reasons for its
      progressive increase in frequency.

PMID- 15984294
TI  - [What is the value of allergologic tests for the diagnosis and management of
      atopic dermatitis?].
AB  - The prevalence of atopic dermatitis (AD) in children has considerably increased
      in industrialised countries over the past 20-30 years. Determination of the
      interest of supplementary examinations, notably allergological explorations, is
      fundamental for all the practitioners who manage children suffering from the
      disease. ALLERGOLOGICAL TESTS: WHEN AND FOR WHO? Children suffering from eczema
      and describing concomitant manifestations such as urticaria, an oral syndrome or
      asthma should benefit from allergological tests. The latter are conducted as
      markers of the progression in the infant (aged under 24 months) presenting with
      atopic eczema without any concomitant manifestations. Such tests are aimed at
      defining the prognosis of AD and specifying the risk of progression towards an
      asthmatic syndrome. Allergological tests are conducted in the case of severe AD
      of early onset and in the presence of a family history of atopy. ALLERGOLOGICAL
      TESTS: WHICH? They explore immediate and delayed hypersensitivity. They include
      determination of IgE-dependent sensitivity using cutaneous tests or specific IgE
      measurements with validated methods. Allergy to food concerns very young children
      of around 2 years old. The diagnosis of such allergies is based on the efficacy
      of the eviction and oral provocation test, when there is discordance between the
      clinical history and the results of the determination of a specific IgE-related
      sensitivity. Prick-tests are performed to search for contact hypersensitivity,
      more frequent in older children. They are performed for contact allergens, aero
      allergens and foodstuff and are supplemented by interrogation data. The
      pertinence of such tests remains to be determined. ALLERGOLOGICAL TESTS: WHAT
      FOR? An allergic factor enhances AD in one child out of two. Evictions adapted to
      the results of the allergological tests always improve the status of the
      children. They may even modify the natural history of the disease.

PMID- 15984296
TI  - [The value of topical immunosuppressors in the treatment of atopic dermatitis in
      children].
AB  - The use of topical immunosuppressors during treatment of atopic dermatitis is an
      important innovation that reinforces the therapeutic arsenal in this chronic
      disease in children. Two products have been studied in depth: tacrolimus, which
      exists in pomade form at a concentration of 0.1 and 0.03% under the trademark
      Protopic. It is the 0.03% concentration that has been studied in children and
      obtained official indication in children aged over 2. Pimecrolimus marketed under
      the trademark Elidel in the form of a 1% cream has also been studied in depth and
      obtained European marketing authorisation for prescription in children aged over
      2. Unfortunately it is not yet available in France, although it is marketed in
      nearly all countries worldwide. These products decrease the production of
      cytokines by the T-cell lymphocytes when stimulated by the antigen. This effect
      is produced by the inhibition of calcineurine. The clinical efficacy of these two
      products has been demonstrated in many studies in the United States and in
      Europe. Short term efficacy has been demonstrated in comparisons versus a placebo
      or versus grade 2 or 3 corticosteroids. Longer term studies (6 months to one
      year) have confirmed the efficacy. Short-term tolerance to these new treatments
      has been shown, although, as with any new product, the long-term results are
      unknown. Nevertheless, tolerance studies after more than 4 years' use exist. The
      side effects most often reported are local, erythema-like at the start of
      treatment with burning and pruritus. There has been no significant increase in
      the number of bacterial and viral infections compared with control groups. Doubt
      remains regarding viral infections of herpetic origin, notably Kaposi
      Juliusberg's disease, although no significant difference has been observed
      compared with the placebo-treated. No systemic impact has been reported with
      these two products or inhibition of the effect of vaccinations made in infants or
      children. However, care should be taken: not to use the products in patients with
      a history of Kaposi-Juliusberg's disease and any contact with a patient
      exhibiting herpes should be avoided; the photoprotection measures should be
      respected as instructed in the patient insert for the use of tacrolimus.

PMID- 15984295
TI  - [The use of topical corticosteroids in atopic dermatitis in children].
AB  - INTRODUCTION: Topical corticosteroids are the treatment of reference in atopic
      dermatitis in children, but their administration may lead to a certain number of
      side effects. METHODS: They are based on a review of the literature and the
      author's personal experience. RESULTS: Topical corticosteroids are classed in
      four groups: weak, moderate, strong and very strong, depending on their efficacy.
      Their side effects are usually proportional to their efficacy. The complications
      with topical corticosteroids are well known, not only on local but also systemic
      level. Appropriate use of such topicals avoids these side effects, which depend
      on the product used, the age of the child and the extent and age of the lesions.
      DISCUSSION: For the past 50 years, topical corticosteroids represent the most
      effective treatment in the management of atopic dermatitis in children. When used
      correctly, they are safe. Failures are related to corticosteroid phobia and poor
      compliance, and their complications to inappropriate use. The modalities of their
      withdrawal and the interest of immunosuppressive macrolides are discussed.

PMID- 15984297
TI  - [What is the value of non-immunosuppressor therapy in the treatment of atopic
      dermatitis?].
AB  - INTRODUCTION: Atopic dermatitis (AD) is a frequent dermatosis in infants and
      children, the management of which combines measures of prevention and medical
      treatment. METHODS: The efficacy of the various treatments available requires
      rigorous assessment. Our analysis of the literature used the "Pubmed" data bank.
      More specifically, we studied the interest of antihistamines, antibiotics,
      antifungals, essential fatty acids and probiotics during AD in children. RESULTS:
      Concerning antihistamines, only the anti-h1 have been assessed during AD and
      their efficacy appears modest in the papers published. The interest of
      antibiotics and antiseptics, in the absence of documented surinfection, is
      marginal. The management of herpes virus viral infections during AD essentially
      relies on acyclovir. The interest raised by essential fatty acid supplementation
      in atopic patients has not been confirmed in papers published on the subject.
      Although the role of probiotics in the prevention and treatment of AD is
      attractive, intellectually, it has not been validated in large cohort studies.
      CONCLUSION: In the light of this study, many supplementary treatments with
      topical corticosteroids during AD do not resist "evidence-based" clinical trials.
      However, the individual benefits of some of these treatments should not be ruled
      out.

PMID- 15984298
TI  - [What additional measures should be recommended in atopic dermatitis in
      children?].
AB  - The so-called 'adjuvant' measures are an important part of atopic dermatitis (AD)
      consultations. The practitioner is the 'expert' in the patients' eyes in
      prescribing, proposing, counselling and replying to the questions concerning
      moisturizers, thermal spring water cures, the resort to alternative medical, and
      vaccinations. Moisturizers are aimed at rapidly restoring water in the epidermis,
      decreasing the sensitivity to irritants and improving the patients' comfort. The
      available products are usually composed of water, occlusive agents, humidifiers,
      varyingly combined with tensioactive agents, preservatives and perfumes... Their
      short term efficacy has been demonstrated, but no study has shown superiority of
      one product over another. The recommended treatment is 1 to 2 daily applications
      of a cream or lotion, selected among the products having demonstrated their
      efficacy, contained the least amount of irritant or sensitizers, the presentation
      and cost of which is acceptable to the patient. There are no arguments to
      recommend moisturizers in the absence of xerosis, nor for prolonged periods of
      clinical remission. Spring water thermal cures. In France there are many cure
      centres and the spring waters used are distinguished by their clinical or
      physical features. Although there are no studies that clearly establish their
      efficacy in AD, the craze and satisfaction of many patients for spring water
      thermal cures must be taken into consideration, as well as the educational
      dimension, in the hopes that a consensus will be reached and that regular
      assessments be made. Alternative medical practices, such as homeopathy or
      acupuncture, represent a therapeutic alternative chosen by more than one third of
      patients with AD. However, no study has sufficiently demonstrated the interest of
      these alternatives and they cannot therefore be integrated in the validated
      arsenal of treatments. Used in various oriental countries, Chinese herbs have
      been the subject of controlled studies with encouraging results. But the data
      available on safety prompt greater care and do not promote the use of such
      products in children. Vaccination of atopic children is a much debated subject
      among the medical corps, although currently consensual attitude is possible. In
      general, there is no reason to limit or delay the French vaccination calendar of
      an atopic child. Notably vaccination with ROR can be used routinely, even in
      those allergic to eggs. It is sometimes logical to avoid vaccination during
      severe flares of eczema. In the case of documented allergy to eggs, the flu and
      yellow fever vaccinations should be avoided, except in exceptional cases when
      vaccination is made in hospital settings.

PMID- 15984299
TI  - [What environmental measures should be taken for the treatment of atopic
      dermatitis in children and the prevention of other atopic manifestations?].
AB  - The association of atopic dermatitis, asthma and allergy is frequent. Hence, it
      is logical to imagine that eviction of the main indoor allergens (dust mites,
      animal danders) would have a preventive effect on the onset and progression of
      atopic dermatitis and the risk of asthma. Recent epidemiological studies are
      generally negative with regard to primary and also secondary and tertiary
      prevention. Only one study appeared positive; it combined eviction of food
      allergens and of indoor allergens during the first year of life. Other studies
      are warranted to assess the interest and efficacy of eviction of inhalant
      allergens in atopic dermatitis.

PMID- 15984300
TI  - [Atopic dermatitis in children and food allergy: combination or causality? Should
      avoidance diets be initiated?].
AB  - Atopic dermatitis (AD) is one of the first manifestations of the atopic march.
      The natural history of food allergies (FA) is closely related to AD. Sensitivity
      to food is demonstrated with cutaneous tests (prick-tests and atopy patch-tests)
      or the presence of IgE specific to food. A true allergy to a foodstuff is
      revealed by oral provocation tests (OPT) or by improvement during an avoidance
      diet. Ingestion of the food allergen during OPT can provoke an onset of eczema,
      an immediate reaction (urticaria, oedema) or involve other target organs
      (digestive disorders, rhinitis, asthma or anaphylactic shock). Seven allergens
      are responsible for around 90 p. 100 of FA: milk, eggs, wheat, peanuts, nuts, soy
      and fish. The fundamental knowledge acquired demonstrates the implication of food
      allergens in the physiopathogenesis of AD. The assessment of the efficacy of
      avoidance diets is difficult to demonstrate in standardised double-blind studies.
      Their efficacy is demonstrated compared with the natural history of AD. A
      diagnostic algorythm of FA during AD is proposed. An avoidance diet can be
      prescribed on 3 levels: primary, secondary and tertiary prevention. Diagnostic
      dietetics are aimed at initiating a hypoallergenic diet over a short period of 15
      to 21 days when AD is severe and does not permit an allergy assessment. This diet
      is followed by an allergy assessment and OPT to determine the foodstuff
      responsible. Therapeutic dietetics consists in initiating an avoidance diet based
      on the results of the allergy assessment: positive predictive value of specific
      IgE, positivity of oral provocation tests or the re-introduction of the foodstuff
      for one week. Preventive dietetics is aimed at preventing the onset of AD: a
      consensus has been established by the American and European Academies of
      Paediatrics. In conclusion, present knowledge demonstrates that FA is a
      triggering factor for AD and that the avoidance diets based on allergy
      assessments are an essential tool in the treatment of AD. Understanding the
      triggering mechanisms of oral tolerance will permit the development of strategies
      for the prevention and cure of food allergies.

PMID- 15984301
TI  - [Do breast-feeding and "diet" milks have any preventive or curative effect in the
      management of atopic dermatitis in children?].
AB  - A) The preventive interest of infants' food in the onset of atopic dermatitis.
      Measures of prevention of atopic dermatitis concern predisposed children. Most
      studies agree on the protective effect of breast feeding for at least 3 to 4
      months, compared with industrial milk products, on the onset of atopic
      dermatitis. Partial breast feeding is not protective. There is no preventive
      effect of breast feeding on the onset of atopic dermatitis in the absence of a
      family history of atopy. However, a few studies have raised the question of the
      aggravation of eczema during prolonged breast feeding. The "breast fed" group is
      probably not a homogenous group. Mothers' milk contains IgA, TGFb-type cytokines
      and long-chain polyinsaturated fatty acids that may play an important part in the
      acquisition of tolerance to food and the prevention of atopic dermatitis. The
      administration of a protein hydrolysate is preferable in terms of prevention of
      an allergy to a formula based on cow's milk, but does not provide any benefit
      compared with breast feeding. The preventive effect on atopic dermatitis of a
      casein hydrolysate is greater than that of a partial hydrolysate, which itself is
      greater than a formula based on cow's milk. In conclusion, the first preventive
      measure is breast feeding for 3 to 4 months, associated with intensive protein
      hydrolysate in the case of mixed feeding. In the absence of breast feeding,
      intensive hydrolysate is recommended in children at high risk. B) The curative
      interest of infants' food in the management of atopic dermatitis. The curative
      interest implies the responsibility of food in the triggering-off or maintenance
      of atopic dermatitis. This concerns non-diversified infants exhibiting severe or
      moderate eczema concomitant to digestive disorders. In such cases, the diagnosis
      of food allergy should be evoked. If the infant is fed on industrial milk, a test
      diet should be proposed with a hydrolysate or based on amino acids, followed by
      the re-introduction of the formula used previously. If the infant is exclusively
      breast fed, diagnosis of an allergy to one of the foodstuffs ingested by the
      mother should be searched for and treated. Early diagnosis of food allergy in
      infants, before diversification, is the optimal factor of prognosis.

PMID- 15984302
TI  - [Atopic dermatitis and psychological factors].
AB  - The role of stress on the triggering-off of flares of atopic dermatitis (AD) is
      the subject of a consensus. It is understandable because biochemical mediators
      are known to affect the cells implied in AD. The role of more complex
      psychological factors (depression, anxiety, and familial interaction) is highly
      probable but difficult to demonstrate. The psychological impact of AD is
      obviously severe. Psychotherapy provides beneficial effects on the impact but
      also on pruritus and scratching. Its effect on the AD lesions has rarely been
      studied but has been observed in many cases. Psychotropics can be useful but they
      should be handled with care in infants.

PMID- 15984303
TI  - [The role of therapeutic education in the treatment of atopic dermatitis in
      children].
AB  - Atopic dermatitis (AD) is a chronic disease of the skin that has heavy impact on
      the quality of life of children affected and raises the question of compliance,
      which frequently leads to treatment failure. Various problems are at the origin
      of poor compliance, such as the progressive loss of parents' motivation, the
      complexity of treatments, the corticosteroid phobia of health care workers and
      patients, and the side effects induced by treatment, their inefficiency and their
      cost. Therapeutic training is aimed at helping the patients to cope with their
      disease and to avoid the related complications. Its aim is to permit patients,
      and those who surround them, to acquire competence and sufficient knowledge so as
      to become autonomous. This acquisition and appropriation of competence by the
      patients requires personalised surveillance. Hence, therapeutic education is a
      continuous process of accompanying the patient throughout training. It is not a
      substitute to treatment but is conducted in parallel, to enable the patients to
      optimize their quality of life. Therapeutic training is already recognised as a
      crucial element in the management of many diseases. Despite the difficulties
      encountered, educational centres would clearly improve the management of AD.

PMID- 15984304
TI  - [How should severe and chronic atopic dermatitis in children be managed?].
AB  - Severe atopic dermatitis in children is rare. When prescribing exceptional
      treatments (because of failure with classical drugs such as topical
      corticosteroids or topical immunosuppressors), it is important to ensure that the
      child is not suffering from an atopic dermatitis that has not been handled
      correctly. This assessment may require short hospitalisation. When the severity
      and rebellious nature of the atopic dermatitis with regard to routine treatment
      has been confirmed, exceptional treatment is envisaged. Currently, the treatment
      that is mastered in children remains cyclosporine, although marketing
      authorisation has not been granted in this indication. The side effects and
      notably nephrotoxicity justify the careful prescription of this drug with regular
      controls, and the opinion of a paediatric nephrologist. Other immunosuppressive
      treatments such as azathioprine, mycophenolate mofetil or even interferon gamma
      have rarely been studied in children, nor particularly in adults, and usually
      only in open studies. Their safe use in children, in the indication of severe
      atopic dermatitis obviously warrants comparative studies in large cohorts.
      Phototherapy should not be banned, even in this paediatric population, but
      modalities should be further defined, taking into account the real practical
      possibilities of this type of treatment, depending on the patients' age, and with
      long-term monitoring. Antileucotrienes have not yet sufficiently demonstrated
      their efficacy. In such severe forms, ideally, there should be the possibility of
      defining the predictable factors of efficacy and tolerance in each patient
      (biologically or with in vitro tests) that would optimise the use of these
      exceptional treatments, or even new molecules, in well targeted indications. The
      golden rule remains: patience, explanation, education, observation, monitoring
      and availability.

PMID- 15984305
TI  - [Atopic dermatitis: epidemiology in France, definitions, natural history,
      association with other atopic manifestations, severity scores and quality of
      life].

PMID- 15984306
TI  - [Physiopathological bases of atopic dermatitis].

PMID- 15984307
TI  - [What is the value of allergologic tests in the diagnosis and management of
      atopic dermatitis in children?].

PMID- 15984308
TI  - [What is the treatment for atopic dermatitis flares in children?].

PMID- 15984309
TI  - [Can vaccination of an atopic child influence the course of the disease? Should
      one recommend or contraindicate vaccines in children with atopic dermatitis?].

PMID- 15984310
TI  - [Food allergy, environment and primary and secondary prevention of atopic
      dermatitis].

PMID- 15984311
TI  - [What are means of preventing flares and the adjuvant measures to be taken in
      atopic dermatitis in children?].

PMID- 15984312
TI  - [How should severe and chronic atopic dermatitis be managed in children?].

PMID- 15984313
TI  - [The management of atopic dermatitis in children by dermatologists,
      paediatricians, general practitioners and allergologists: a national survey on
      practice patterns].
AB  - A national survey on practice habits was conducted from June to August 2004
      within the framework of the consensus conference on the management of atopic
      dermatitis (AD) in children. The telephone survey involved a sample population of
      100 dermatologists, 100 paediatricians, 100 general practitioners and 100
      allergologists. The survey demonstrated the interest that those interviewed had
      with regard to AD and the frequency of the disease in daily practice. The severe
      forms are usually seen by the allergologists and dermatologists, but
      paediatricians also see a lot of mild or moderate AD in infants under the age of
      2. The modalities of its management vary depending on the specialization, notably
      with regard to topical treatment. Hygiene and environment counselling provided by
      the practitioners is fairly homogenous. These results will help to assess the
      future modifications in practising habits, following the diffusion of the
      guidelines from the consensus conference.

PMID- 15984314
TI  - Genetics and environmental risk factors associated with asthma in schoolchildren.
AB  - OBJECTIVES: The objective of this study was to investigate the genetic and
      environmental risk factors associated with asthma among Qatari school children
      aged 6-12 years. DESIGN: A cross-sectional study was performed. The International
      study of asthma and allergies in childhood (ISAAC) and some additional
      questionnaires were used to collect the data of the school children between Feb
      2003 and Feb 2004. SETTING: Government primary schools in the State of Qatar.
      SUBJECTS: A multistage sampling design was used and a representative sample of
      3500 children were targeted for this study. Of these, 3204 parents (91.6%) of the
      children agreed to participate in this study. RESULTS: Of the total study sample
      3204 school children living in urban and semi urban areas, 51.9% were boys and
      48.1% girls. Their mean age was 8.92 +/- 1.89. The population sample had a high
      prevalence rate of asthma (19.8%) and allergic rhinitis 30.3%. The frequency of
      asthma, allergic rhinitis and eczema among parents reflected the same pattern as
      that seen in the children. Environmental risk factors associated with asthma were
      pets at home, allergic to certain food or medicine, smoking history among parents
      or elder siblings (p<0.0001). A stepwise logistic regression analysis results
      showed that allergic to food and medicine, history of asthma in father, mother,
      siblings and asthma in second degree relatives and smoking habit of father were
      significant predictors for asthma after adjusting age and sex and other
      confounding covariates in the model. CONCLUSION: The present study revealed that
      the family history of asthma contributed more to childhood asthma than indoor and
      outdoor environmental factors. Boys were found more asthmatic than girls. The
      results of this study support the hypothesis that asthma is a multi-factorial
      disease related to both familial and environmental influences.

PMID- 15984315
TI  - Development of new IgE specificities to hymenoptera allergens during venom
      specific immunotherapy.
AB  - BACKGROUND: Despite the benefits of specific immunotherapy (SIT) being clinically
      well documented for allergic diseases, new IgE specificities to SIT extract
      allergens could be induced during the treatment. The authors evaluated these
      changes in patients allergic to Hymenoptera. METHODS: Six patients allergic to
      Hymenoptera venom were included in the study. Specific IgE (sIgE) levels
      determination and IgE immunoblots to Apis mellifera, Vespula spp. and Polistes
      spp. venom were performed before and after one year of SIT. RESULTS: All patients
      had sIgE levels reduction, after the first year of treatment, except one in whom
      there was an increase in sIgE levels to Apis mellifera venom, and two patients
      that maintained a similar value for Vespula spp. venom sIgE before and after one
      year of treatment. The immunoblot analysis revealed that most of the bands
      detected before beginning SIT, decreased in intensity or disappeared after one
      year of treatment. 3/6 patients developed new IgE specificities to venom
      extracts: one patient to the venom allergens in the treatment, other patient to
      allergens in other venom and another patient to both. After one year of treatment
      one of these patients tolerated a field sting by the corresponding insect. The
      newly recognised proteins were all minor allergens. CONCLUSION: These results
      confirm that sIgE levels tend to reduce during SIT, and the bands identifying
      some allergens in the blot tend to decrease or disappear. Nonetheless venom SIT
      can be responsible for the induction of new sensitisations to other venom
      allergens, apparently without clinical relevance.

PMID- 15984316
TI  - "Minor" hemoglobinopathies: a risk factor for asthma.
AB  - BACKGROUND: Thalassemia, sickle cell disease and other hemoglobinopathies are not
      rare in Portugal and European Mediterranean area. Homozygotic patients present
      major hematological disease but heterozygotic minor assymptomatic forms are
      frequent, mainly thalassemia minor and sickle cell trait. In these cases
      mycrocytosis with decrease or red cell volume and mean corpuscular volume or
      abnormal rigid erythrocytes are found and can lead to hemorheologic disturbances.
      The purpose of this study is to evaluate the incidence of asthma in
      hemoglobinopatic patients allergic to house dust mites. METHOD: From 4.000
      patients seen in the last 5 years in an out-patient allergy clinic, 63 cases of
      hemoglobinopathies have been confirmed by red cell count, hemoglobin
      electrophoresis, assays of hemoglobin A2, Fc, and S, and sickle cell test. All
      these patients had allergic disease characterized by clinical history, skin prick
      test to aeroallergens total and specific IgE (RAST-CAP-FEIA) and respiratory
      function evaluation. RESULTS: 66 Hemoglobinopathies: Betathalassemia 61 cases,
      Betadelta thalassemia 2, sickle cell trait 2, Hemoglobin C, 1.57 patients have
      respiratory allergy, rhinitis in 14 cases of thalassemia and 1 of hemoglobin C,
      asthma with or without rhinitis in 41 cases of thalassemia and 1 case of sickle
      cell trait, the other 6 cutaneous allergy. Therefore asthma was present in 75.0%
      of the respiratory allergic patients and rhinitis only in 25.0%. In contrast in a
      control group of 491 respiratory allergic patients wihout hemoglobinopathies, 57%
      has asthma and 43% only rhinitis. CONCLUSION: The prevalence of asthma is higher
      in thalassemia minor and sickle cell trait (p<0.05 Square chi test).
      Hemorheological changes probably a greater rigidity of red blood cells in
      capillary bed can contribute to changes in bronchial circulation and bronchial
      hypereactivity. Detection of hemoglobinopathies must be done in asthmatic
      patients with slight anemia or mycrocytosis.

PMID- 15984317
TI  - Allergy to sunflower seeds.
AB  - A case of oral syndrome after eating sunflower seeds is reported. Sensitization
      has been probably through inhalant route when using these seeds to feed birds.
      Skin prick tests with a fresh macerate of sunflower seeds has been clearly
      positive (greater than histamine control) but commercial extracts have given
      borderline positivity and specific IgE to sunflower was strongly positive.

PMID- 15984318
TI  - Urban versus rural environment--any differences in aeroallergens sensitization in
      an allergic population of Cova da Beira, Portugal?
AB  - Cova da Beira is an interior central region of Portugal, with a population of
      93000 inhabitants divided in urban and rural living areas. The aim of this study
      was to access the prevalence of aeroallergens sensitisation in an allergic
      population, according to the urban and the rural environmental exposure and
      according to age. 1096 patients observed for suspected allergic symptoms, for a
      five-year period (1995-2000) were submitted to skin prick tests and were included
      in this study. They were divided in two environmental exposure groups (A: urban;
      B: rural) and in to four age subgroups (subgroup I: < or = 10yr; subgroup II: 11
      20yr; subgroup III: 21-40yr; subgroup IV: >40yr). The total population included
      444 male (40.5%) and 652 female (59.4%) with an average age of 26.5 +/- 17.2 yr.
      83% of the 1096 performed SPT were positive. The frequency of aeroallergens
      sensitisation, comparing the urban versus the rural environment, was
      respectively: D. pteronyssinus 32% and 34.7%, D. farinae 28.5% and 30.7%, moulds
      mixture 15.3% and 12%, cat dander 17.1% and 15.2%, dog dander 11% and 10%,
      grasses mixture 51.3% and 36.4%, Parietaria judaica 29.4% and 14%, Olea europea
      30.2% and 23.3%. The sensitisation to indoor aeroallergens, was similar in all
      the age subgroups and it was lower than that to pollens. There were important
      differences concerning the pollen sensitisation, when comparing the urban and the
      rural environmental exposure. We admit that pollution could enhance the
      sensitisation to pollens in the urban environment.

PMID- 15984319
TI  - An overview of transmissible spongiform encephalopathies.
AB  - Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative
      disorders of humans and animals associated with an accumulation of abnormal
      isoforms of prion protein (PrP) in nerve cells. The pathogenesis of TSEs involves
      conformational conversions of normal cellular PrP (PrP(c)) to abnormal isoforms
      of PrP (PrP(Sc)). While the protein-only hypothesis has been widely accepted as a
      causal mechanism of prion diseases, evidence from more recent research suggests a
      possible involvement of other cellular component(s) or as yet undefined
      infectious agent(s) in PrP pathogenesis. Although the underlying mechanisms of
      PrP strain variation and the determinants of interspecies transmissibility have
      not been fully elucidated, biochemical and molecular findings indicate that
      bovine spongiform encephalopathy in cattle and new-variant Creutzfeldt-Jakob
      disease in humans are caused by indistinguishable etiological agent(s).
      Cumulative evidence suggests that there may be risks of humans acquiring TSEs via
      a variety of exposures to infected material. The development of highly precise
      ligands is warranted to detect and differentiate strains, allelic variants and
      infectious isoforms of these PrPs. This article describes the general features of
      TSEs and PrP, the current understanding of their pathogenesis, recent advances in
      prion disease diagnostics, and PrP inactivation.

PMID- 15984320
TI  - The molecular biology of bovine immunodeficiency virus: a comparison with other
      lentiviruses.
AB  - Bovine immunodeficiency virus (BIV) was first isolated in 1969 from a cow, R-29,
      with a wasting syndrome. The virus isolated induced the formation of syncytia in
      cell cultures and was structurally similar to maedi-visna virus. Twenty years
      later, it was demonstrated that the bovine R-29 isolate was indeed a lentivirus
      with striking similarity to the human immunodeficiency virus. Like other
      lentiviruses, BIV has a complex genomic structure characterized by the presence
      of several regulatory/accessory genes that encode proteins, some of which are
      involved in the regulation of virus gene expression. This manuscript aims to
      review biological and, more particularly, molecular aspects of BIV, with emphasis
      on regulatory/accessory viral genes/proteins, in comparison with those of other
      lentiviruses.

PMID- 15984321
TI  - Hepatitis E viruses in humans and animals.
AB  - Hepatitis E virus (HEV) is an emerging pathogen belonging to a newly recognized
      family of RNA viruses (Hepeviridae). HEV is an important enterically transmitted
      human pathogen with a worldwide distribution. It can cause sporadic cases as well
      as large epidemics of acute hepatitis. Epidemics are primarily waterborne in
      areas where water supplies are contaminated with HEV of human origin. There is
      increasing evidence, however, that many animal species are infected with an
      antigenically similar virus. A recently isolated swine virus is the best
      candidate for causing a zoonotic form of hepatitis E. The virus is serologically
      cross-reactive with human HEV and genetically very similar, and the human and
      swine strains seem to be cross-infective. Very recent evidence has also shown
      that swine HEV, and possibly a deer strain of HEV, can be transmitted to humans
      by consumption of contaminated meat. In this review, we discuss the prevalence,
      pathogenicity, diagnosis and control of human HEV, swine HEV, the related avian
      HEV and HEV in other hosts and potential reservoirs.

PMID- 15984322
TI  - Bovine torovirus (Breda virus) revisited.
AB  - Bovine torovirus (BoTV) is a pleomorphic virus with a spike-bearing envelope and
      a linear, non-segmented, positive-sense single-stranded RNA genome. This kidney
      shaped virus is associated with diarrhea in calves and apparently has a worldwide
      distribution. This review provides details of the history and taxonomy of BoTV
      since its discovery in 1979. Information about virion morphology and
      architecture, antigenic and biological properties, viral genome, protein
      composition, thermal and chemical stability, and pH and proteolytic enzymes
      resistance is also summarized. A major focus of this review is to postulate a
      possible epidemiological cycle for BoTV, based on epidemiological data obtained
      in our studies and other published data, and progressing from the newborn calf to
      the adult animal. The distribution, host range, pathogenesis, disease and
      clinical signs (under experimental and natural exposure), pathology, diagnosis,
      prevention, treatment and control of BoTV infections are also described. In
      addition, a discussion of the zoonotic implications of torovirus-like particles
      detected in patients with gastroenteritis that resemble and cross-react with BoTV
      is presented. Hopefully, the findings described here will alert others to the
      existence of BoTV in cattle and its contribution to the diarrheal disease
      complex. This review also highlights the need for continual vigilance for
      potential zoonotic viruses belonging to the order Nidovirales, such as the SARS
      coronavirus.

PMID- 15984323
TI  - The use of nuclear ribosomal DNA markers for the identification of bursate
      nematodes (order Strongylida) and for the diagnosis of infections.
AB  - Many bursate nematodes are of major importance to animal health. Animals are
      often parasitized by multiple species that differ in their prevalence, relative
      abundance and/or pathogenicity. Implementation of effective management strategies
      for these parasites requires reliable methods for their detection in hosts,
      identification to the species level and measurement of intensity of infection.
      One major problem is the difficulty of accurately identifying and distinguishing
      many species of bursate nematode because of the remarkable morphological
      similarity of their eggs and larvae. The inability to identify, with confidence,
      individual nematodes (irrespective of their life-cycle stage) to the species
      level by morphological methods has often led to a search for species-specific
      genetic markers. Studies over the past 15 years have shown that sequences of the
      internal transcribed spacers of ribosomal DNA provide useful genetic markers,
      providing the basis for the development of PCR-based diagnostic tools. Such
      molecular methods represent powerful tools for studying the systematics,
      epidemiology and ecology of bursate nematodes and, importantly, for the specific
      diagnosis of infections in animals and humans, thus contributing to improved
      control and prevention strategies for these parasites.

PMID- 15984324
TI  - The role of dendritic cells in shaping the immune response.
AB  - Dendritic cells are central to the initiation of primary immune responses. They
      are the only antigen-presenting cell capable of stimulating naive T cells, and
      hence they are pivotal in the generation of adaptive immunity. Dendritic cells
      also interact with and influence the response of cells of the innate immune
      system. The manner in which dendritic cells influence the responses in cells of
      both the innate and adaptive immune systems has consequences for the bias of the
      adaptive response that mediates immunity to infection after vaccination or
      infection. It also provides an opportunity to intervene and to influence the
      response, allowing ways of developing appropriate vaccination strategies. Mouse
      and human studies have identified myeloid, lymphoid and plasmacytoid dendritic
      cells. Studies in domesticated animals with agents of specific infectious
      diseases have confirmed the applicability of certain of the generic models
      developed from mice or from in vitro studies on human cells. In vivo and ex vivo
      studies in cattle have demonstrated the existence of a number of subpopulations
      of myeloid dendritic cells. These cells differ in their ability to stimulate T
      cells and in the cytokines that they produce, observations clearly having
      important implications for the bias of the T-cell response. Dendritic cells also
      interact with the innate immune system, inducing responses that potentially bias
      the subsequent adaptive response.

PMID- 15984325
TI  - Genetic variation and responses to vaccines.
AB  - Disease is a major source of economic loss to the livestock industry.
      Understanding the role of genetic factors in immune responsiveness and disease
      resistance should provide new approaches to the control of disease through
      development of safe synthetic subunit vaccines and breeding for disease
      resistance. The major histocompatibility complex (MHC) has been an important
      candidate locus for immune responsiveness studies. However, it is clear that
      other loci play an important role. Identifying these and quantifying the relative
      importance of MHC and non-MHC genes should result in new insights into host
      pathogen interactions, and information that can be exploited by vaccine
      designers. The rapidly increasing information available about the bovine genome
      and the identification of polymorphisms in immune-related genes will offer
      potential candidates that control immune responses to vaccines. The bovine MHC,
      BoLA, encodes two distinct isotypes of class II molecules, DR and DQ, and in
      about half the common haplotypes the DQ genes are duplicated and expressed. DQ
      molecules are composed of two polymorphic chains whereas DR consists of one
      polymorphic and one non-polymorphic chain. Although, it is clear that MHC
      polymorphism is related to immune responsiveness, it is less clear how different
      allelic and locus products influence the outcome of an immune response in terms
      of generating protective immunity in outbred animals. A peptide derived from foot
      and-mouth disease virus (FMDV) was used as a probe for BoLA class II function.
      Both DR and DQ are involved in antigen presentation. In an analysis of T-cell
      clones specific for the peptide, distinct biases to particular restriction
      elements were observed. In addition inter-haplotype pairings of DQA and DQB
      molecules produced functional molecules, which greatly increases the numbers of
      possible restriction elements, compared with the number of genes, particularly in
      cattle with duplicated DQ genes. In a vaccine trial with several peptides derived
      from FMDV, BoLA class II DRB3 polymorphisms were correlated with both protection
      and non-protection. Although variation in immune responsiveness to the FMDV
      peptide between different individuals is partly explainable by BoLA class II
      alleles, other genetic factors play an important role. In a quantitative trait
      locus project, employing a second-generation cross between Charolais and Holstein
      cattle, significant sire and breed effects were also observed in T-cell, cytokine
      and antibody responses to the FMDV peptide. These results suggest that both MHC
      and non-MHC genes play a role in regulating bovine immune traits of relevance to
      vaccine design. Identifying these genes and quantifying their relative
      contributions is the subject of further studies.

PMID- 15984326
TI  - Advances in mucosal vaccination.
AB  - Pathogens that enter the body via mucosal surfaces face unique defense mechanisms
      that combine the innate barrier provided by the mucus layer with an adaptive
      response typified by the production and transepithelial secretion of pathogen
      specific IgA. Both the measurement and induction of mucosal responses pose
      significant challenges for experimental and practical application and may need to
      be adapted to the species under study. In particular, for livestock, immunization
      procedures developed in small rodent models are not always effective in large
      animals or compatible with management practices. This paper reviews the latest
      advances in our understanding of the processes that lead to secretory IgA
      responses and how this relates to the development of mucosal immunization
      procedures and adjuvants for veterinary vaccines. In addition, it highlights the
      complex interactions that can take place between the pathogen and the host's
      immune response, with specific reference to Chlamydia/Chlamydophila infections in
      sheep.

PMID- 15984327
TI  - Vaccinating against zoonotic parasitic diseases: myth or reality?
AB  - The largely unanticipated difficulties of parasite vaccine development have led
      us to a renewed awareness of the survival strategies evolutionarily embedded
      within parasites over hundreds of millions of years. We have grown to appreciate
      that efforts to disrupt parasite-host relationships are substantially compounded
      by our incomplete understanding of the complex immune responses that occur in the
      naturally infected host. Given the inability to transfer laboratory successes to
      field trials, research is leading us to conclude that genetically defined animal
      models may not be good predictors of the unique and disparate protective immune
      responses one can expect from the genetically heterogeneous populations of
      animals that represent the parasite's natural environment. This is further
      compounded by the abundance of mechanisms parasites have created for themselves
      to defend against immune intervention. Thus, in the never-ending saga of vaccine
      development, it is only appropriate that pitfalls and advancements be critiqued
      as they apply across parasite groups, with a look towards promising technologies
      that may propel this field to the level of scientific achievement once envisaged.

PMID- 15984328
TI  - Vaccination against classical swine fever virus: limitations and new strategies.
AB  - The most widely used vaccines for the control of classical swine fever (CSF) in
      countries where it is endemic are live attenuated virus strains, which are highly
      efficacious, inducing virtually complete protection against challenge with
      pathogenic virus. In the European Union (EU), the combination of prophylactic
      mass vaccination and culling of infected pigs in endemic regions has made it
      possible to almost eradicate the disease. However, it is not possible to
      discriminate between infected and vaccinated animals, thus hampering disease
      control measures that rely on serology. Therefore, vaccination was banned at the
      end of 1990 before the internal common market was established in the EU.
      Vaccination is allowed only in severe emergencies. In addition, there are strict
      restrictions on the international trade in pig products from countries using
      vaccination. To circumvent these problems, marker vaccines which allow
      differentiation of infected from vaccinated animals (DIVA) have been developed.
      There are several approaches, ranging from protective peptides, single expressed
      proteins, naked DNA and chimeric viruses. To date, two subunit vaccines based on
      the E2 glycoprotein are commercially available and have been tested extensively
      for their efficacy. The accompanying discriminatory tests are based on an ELISA
      detecting another viral glycoprotein, the E(rns). The subunit vaccines were found
      to be less efficacious than live attenuated vaccines. In addition, the currently
      available discriminatory tests do not provide high enough specificity and
      sensitivity. Although there is an urgent need for more advanced marker vaccines
      and better discriminatory tests, the development of new DIVA vaccines against CSF
      is hampered by the small market potential for these products.

PMID- 15984329
TI  - Cell-based cancer gene therapy: breaking tolerance or inducing autoimmunity?
AB  - This review examines the mechanisms involved in anti-tumor immunity and how
      peptides present in many tumor types (tumor-associated antigens) are recognized
      by T cells from tumor-bearing cancer patients. Tumor-associated antigens are
      derived from proteins that are also expressed in normal cells. It is predicted
      that immune responses to such peptides will be compromised by self-tolerance or
      that stimulation of effective immune responses will be accompanied by
      autoimmunity. We also consider that the immunity induced against two
      autoantigens, which are highly conserved in vertebrates, involve qualitatively
      different mechanisms, such as the production of antibodies and cell-mediated
      immune responses. However, both pathways lead to tumor immunity and identical
      phenotypic manifestations of autoimmunity. Appropriate selection of the optimal
      tumor antigen is critical for the induction of an anti-tumor immune response.
      Thus, we stress that the methods for antigen presentation using dendritic cells
      play a critical role in the development of tumor vaccines, to break immune
      tolerance and induce a strong immune response against them. The viability and
      feasibility of expansion of canine dendritic cells from bone marrow and
      peripheral blood ex vivo for the treatment of spontaneous cancers in dogs is also
      discussed.

PMID- 15984330
TI  - The design of randomized controlled trials of veterinary vaccines.
AB  - Randomized controlled trials of veterinary vaccines are essential if we are to
      have a reasonable understanding of how those vaccines can be expected to perform
      when used in the field. This manuscript reviews a few (but certainly not all) of
      the key elements that need to be considered in the design of veterinary vaccine
      trials. The first step in the design of such a trial is to have a clear statement
      of the objective of the trial that reflects what is expected of the vaccine (e.g.
      should it minimize clinical disease or does it need to prevent infection?).
      Because domestic animals are often managed in groups, the 'unit of concern' used
      in a vaccine trial becomes of great importance. Whether the trial should be
      carried out at the individual or group level will depend on the objectives of the
      trial and the extent of concern about 'group effects' affecting the trial. Sample
      sizes will also be influenced heavily by the choice of unit of concern and the
      nature of the primary outcome being assessed. Finally, while there is no easy
      solution (except to conduct group-level trials, which may be logistically
      impossible), the potential for group effects to influence the trial outcome must
      be considered.

PMID- 15984331
TI  - Commercialization of veterinary viral vaccines.
AB  - If vaccines are to reliably prevent disease, they must be developed, produced and
      quality-controlled according to very strict regulations and procedures.
      Veterinary viral vaccine registrations are governed by different rules in
      different countries, but these rules all emphasize that the quality of the raw
      materials--the cells, eggs, animals or plants that are used in production--need
      to be carefully controlled. The veterinary vaccine business is also very cost
      conscious. Emphasis over the last 5-10 years has therefore been to develop
      culture systems that minimize labor and sterility problems and thus provide for
      reliable and cost-effective production. Implementing these often more complex
      systems in a production environment takes considerable effort, first in scale-up
      trials and further down the line in convincing production personnel to change
      their familiar system for something new and possibly untried. To complete scale
      up trials successfully, it is absolutely necessary to understand the biochemistry
      of the cells and the influence of the virus on the cells under scale-up and later
      production conditions. Once a viral product can be produced on a large scale, it
      is imperative that the quality of the end-product is controlled in an intelligent
      way. One needs to know whether the end-product performs in the animal as was
      intended during its conception in the research and development department. The
      development of the appropriate tests to demonstrate this plays an important role
      in the successful development of a vaccine.

PMID- 15984332
TI  - Commercialization of plant-based vaccines from research and development to
      manufacturing.
AB  - The benefits of using plant-based oral vaccines are discussed. Transgenic maize
      expressing an antigen of transmissible gastroenteritis virus (TGEV) is reported
      as a model to demonstrate efficacy. Young pigs that were fed the TGEV corn orally
      were protected against challenge with virulent TGEV. Additional parameters
      important in providing a reliable and consistent supply of plant-based vaccines
      are discussed. Finally, vaccines developed in maize are evaluated for their
      potential to contaminate either the food supply or the environment.

PMID- 15984333
TI  - Advances in PCR technology.
AB  - Since the discovery of the polymerase chain reaction (PCR) 20 years ago, an
      avalanche of scientific publications have reported major developments and changes
      in specialized equipment, reagents, sample preparation, computer programs and
      techniques, generated through business, government and university research. The
      requirement for genetic sequences for primer selection and validation has been
      greatly facilitated by the development of new sequencing techniques, machines and
      computer programs. Genetic libraries, such as GenBank, EMBL and DDBJ continue to
      accumulate a wealth of genetic sequence information for the development and
      validation of molecular-based diagnostic procedures concerning human and
      veterinary disease agents. The mechanization of various aspects of the PCR assay,
      such as robotics, microfluidics and nanotechnology, has made it possible for the
      rapid advancement of new procedures. Real-time PCR, DNA microarray and DNA chips
      utilize these newer techniques in conjunction with computer and computer
      programs. Instruments for hand-held PCR assays are being developed. The PCR and
      reverse transcription-PCR (RT-PCR) assays have greatly accelerated the speed and
      accuracy of diagnoses of human and animal disease, especially of the infectious
      agents that are difficult to isolate or demonstrate. The PCR has made it possible
      to genetically characterize a microbial isolate inexpensively and rapidly for
      identification, typing and epidemiological comparison.

PMID- 15984334
TI  - Microarrays in veterinary diagnostics.
AB  - Microarrays have numerous applications in the clinical setting, and these uses
      are not confined to the study of common human diseases. Indeed, the high
      throughput technology affects clinical diagnostics in a variety of contexts, and
      this is reflected in the increasing use of microarray-based tools in the
      development of diagnostic and prognostic tests and in the identification of novel
      therapeutic targets. While much of the value of microarray-based experimentation
      has been derived from the study of human disease, there is equivalent potential
      for its role in veterinary medicine. Even though the resources devoted to the
      study of animal molecular diagnostics may be less than those available for human
      research, there is nonetheless a growing appreciation of the value of genome-wide
      information as it applies to animal disease. Therefore, this review focuses on
      the basics of microarray experimentation, and how this technology lends itself to
      a variety of diagnostic approaches in veterinary medicine.

PMID- 15984336
TI  - The impact of vaccines and the future of genetically modified poxvirus vaccines
      for poultry.
AB  - The regular use of live or killed vaccines against infectious agents has
      remarkably improved the efficiency of poultry production. In some cases
      eradication of disease has been possible when the pathogen is antigenically
      stable and confined to a certain geographical area. In other instances monovalent
      or polyvalent live or killed vaccines have been effective in reducing mortality
      and morbidity. Many conventional vaccines are developed by trial and error and
      basic information about their genetic make-up is not known. While the poultry
      industry has benefited from the regular use of conventional vaccines, there is
      need for a new generation of effective vaccines that require minimal handling of
      birds during administration. Using molecular techniques, it is possible to
      identify the genes associated with virulence and protection. In genetically
      engineered vaccines, genes that encode protective antigens can be expressed in
      bacterial or viral vectors. In this regard, avianpox virus vectors appear to be
      promising for the generation of polyvalent vaccines expressing antigens from
      multiple pathogens.

PMID- 15984335
TI  - Application of DIVA vaccines and their companion diagnostic tests to foreign
      animal disease eradication.
AB  - The risk of foreign animal disease introduction continues to exist despite
      Canada's strict regulations concerning the importation of animals and animal
      products. Given the rapidity with which these diseases can spread, especially in
      areas with dense livestock populations, eradication efforts which rely solely on
      quarantine and stamping-out measures can present a formidable undertaking. This,
      combined with growing economic and ethical considerations, has led to renewed
      interest in the use of vaccination as a tool in controlling foreign animal
      disease outbreaks. Vaccination has effects at the individual and population
      levels. Efficacious vaccines reduce or prevent clinical signs without necessarily
      preventing virus replication. They may also increase the dose of virus needed to
      establish an infection and/or reduce the level and duration of virus shedding
      following infection. Vaccine effectiveness within a population is a function of
      its ability to reduce virus transmission. Transmission is best described by the
      reproductive ratio, R, which is defined as the average number of new infections
      caused by one infectious individual. By helping to reduce the R-value below 1,
      vaccination can be an effective adjunct in abbreviating an outbreak.
      Nevertheless, vaccination can also complicate serological surveillance activities
      that follow eradication, if the antibody response induced by vaccination is
      indistinguishable from that which follows infection. This disadvantage can be
      overcome by the use of DIVA vaccines and their companion diagnostic tests. The
      term DIVA (differentiating infected from vaccinated individuals) was coined in
      1999 by J. T. van Oirschot of the Central Veterinary Institute, in The
      Netherlands. It is now generally used as an acronym for 'differentiating infected
      from vaccinated animals'. The term was originally applied to the use of marker
      vaccines, which are based on deletion mutants of wild-type microbes, in
      conjunction with a differentiating diagnostic test. The DIVA strategy has been
      extended to include subunit and killed whole-virus vaccines. This system makes
      possible the mass vaccination of a susceptible animal population without
      compromising the serological identification of convalescent individuals. The DIVA
      approach has been applied successfully to pseudorabies and avian influenza
      eradication, and has been proposed for use in foot-and-mouth disease and
      classical swine fever eradication campaigns. This paper will survey current
      vaccine technology, the host immune response, and companion diagnostic tests that
      are available for pseudorabies, foot-and-mouth disease, classical swine fever and
      avian influenza.

PMID- 15984337
TI  - Relationship between vaccination and management in assuring profitable pork
      production.

PMID- 15984338
TI  - Cytotoxic T lymphocytes in protection against equine infectious anemia virus.
AB  - Cytotoxic T lymphocytes (CTL) are associated with virus control in horses
      infected with equine infectious anemia virus (EIAV). Early in infection, control
      of the initial viremia coincides with the appearance of CTL and occurs before the
      appearance of neutralizing antibody. In carrier horses, treatment with
      immunosuppressive drugs results in viremia before a change in serum neutralizing
      antibody occurs. Clearance of initial viremia caused by other lentiviruses,
      including human immunodeficiency virus-1 and simian immunodeficiency virus, is
      also associated with CTL and not neutralizing antibody. In addition, depletion of
      CD8+ cells prior to infection of rhesus monkeys with simian immunodeficiency
      prevents clearance of virus and the same treatment of persistently infected
      monkeys results in viremia. Cats given adoptive transfers of lymphocytes from
      vaccinated cats were protected and the protection was MHC-restricted, occurred in
      the absence of antiviral humoral immunity, and correlated with the transfer of
      cells with feline immunodeficiency virus-specific CTL and T-helper lymphocyte
      activities. Therefore, a lentiviral vaccine, including one for EIAV, needs to
      induce CTL. Based on initial failures to induce CTL to EIAV proteins by any means
      other than infection, we attempted to define an experimental system for the
      evaluation of methods for CTL induction. CTL epitopes restricted by the ELA-A1
      haplotype were identified and the MHC class I molecule presenting these peptides
      was identified. This was done by expressing individual MHC class I molecules from
      cDNA clones in target cells. The target cells were then pulsed with peptides and
      used with effector CTL stimulated with the same peptides. In a preliminary
      experiment, immunization of three ELA-A1 haplotype horses with an Env peptide
      restricted by this haplotype resulted in CTL in peripheral blood mononuclear
      cells (PBMC) which recognized the Env peptide and virus-infected cells, but the
      CTL response was transient. Nevertheless there was significant protection against
      clinical disease following EIAV challenge of these immunized horses when compared
      with three control horses given the same virus challenge. These data indicated
      that responses to peptides in immunized horses needed to be enhanced. Optimal CTL
      responses require help from CD4+ T lymphocytes, and experiments were done to
      identify EIAV peptides which stimulated CD4+ T lymphocytes in PBMC from infected
      horses with different MHC class II types. Two broadly cross-reactive Gag peptides
      were identified which stimulated only an interferon gamma response by CD4+ T
      lymphocytes, which indicated a T helper 1 response is needed for CTL stimulation.
      Such peptides should facilitate CTL responses; however, other problems in
      inducing protection against lentiviruses remain, the most significant of them
      being EIAV variants that can escape both CTL and neutralizing antibody. A
      possible solution to CTL escape variants is the induction of high-avidity CTL to
      multiple EIAV epitopes.

PMID- 15984339
TI  - Complexities of the pathogenesis of Mannheimia haemolytica and Haemophilus somnus
      infections: challenges and potential opportunities for prevention?
AB  - Progress in producing improved vaccines against bacterial diseases of cattle is
      limited by an incomplete understanding of the pathogenesis of these agents. Our
      group has been involved in investigations of two members of the family
      Pasteurellaceae, Mannheimia haemolytica and Haemophilus somnus, which illustrate
      some of the complexities that must be confronted. Susceptibility to M.
      haemolytica is greatly increased during active viral respiratory infection,
      resulting in rapid onset of a severe and even lethal pleuropneumonia. Despite
      years of investigation, understanding of the mechanisms underlying this viral
      bacterial synergism is incomplete. We have investigated the hypothesis that
      active viral infection increases the susceptibility of bovine leukocytes to the
      M. haemolytica leukotoxin by increasing the expression of or activating the beta2
      integrin CD11a/CD18 (LFA-1) on the leukocyte surface. In vitro exposure to
      proinflammatory cytokines (i.e. interleukin-1beta, tumor necrosis factor-alpha
      and interferon-gamma) increases LFA-1 expression on bovine leukocytes, which in
      turn correlates with increased binding and responsiveness to the leukotoxin.
      Alveolar macrophages and peripheral blood leukocytes from cattle with active
      bovine herpesvirus-1 (BVH-1) infection are more susceptible to the lethal effects
      of the leukotoxin ex vivo than leukocytes from uninfected cattle. Likewise, in
      vitro incubation of bovine leukocytes with bovine herpesvirus 1 (BHV-1)
      potentiates LFA-1 expression and makes the cells more responsive to leukotoxin. A
      striking characteristic of H. somnus infection is its propensity to cause
      vasculitis. We have shown that H. somnus and its lipo-oligosaccharide (LOS)
      trigger caspase activation and apoptosis in bovine endothelial cells in vitro.
      This effect is associated with the production of reactive oxygen and nitrogen
      intermediates, and is amplified in the presence of platelets. The adverse effects
      of H. somnus LOS are mediated in part by activation of endothelial cell
      purinergic receptors such as P2X7. Further dissection of the pathways that lead
      to endothelial cell damage in response to H. somnus might help in the development
      of new preventive or therapeutic regimens. A more thorough understanding of M.
      haemolytica and H. somnus virulence factors and their interactions with the host
      might identify new targets for prevention of bovine respiratory disease.

PMID- 15984340
TI  - Challenges confronting feline vaccination.
AB  - Vaccination continues to be a major tool for controlling feline infectious
      diseases, but numerous factors present both challenges and opportunities for
      maintaining and expanding the market for veterinary biologicals. Developing novel
      vaccines is one approach, but in most cases the market for such products will be
      restricted to niche populations; the comparatively smaller quantity of vaccines
      sold may be offset somewhat if available from a limited number of manufacturers.
      A second approach is to produce better formulations of existing vaccines; such
      products would be applicable to larger populations of cats and have greater sales
      potential. But veterinarians must be convinced of the improved product's
      superiority for it to be successful in the marketplace. To ensure that high
      quality, useful and necessary vaccines reach the marketplace, communication
      between veterinarians, the manufacturers of biologicals, and regulatory agencies
      must be enhanced.

PMID- 15984341
TI  - Feline vaccine-associated sarcomas: progress?

PMID- 15984342
TI  - Methodological issues in the design and analysis of epidemiological studies of
      feline vaccine-associated sarcomas.

PMID- 15984344
TI  - Oral vaccines for finfish: academic theory or commercial reality?
AB  - Aquaculture is the fastest growing food-producing sector, providing an acceptable
      supplement to and substitute for wild fish and plants. Increased production
      intensification, particularly in high-value species, involves substantial stress,
      which, as in other captive livestock species, has resulted in outbreaks of major
      diseases and related mortalities. Widespread use of antibiotics has led to the
      development of antibiotic-resistant bacteria and the accumulation of antibiotics
      in the environment and the flesh of fish. Thus, recently effort has been
      dedicated to vaccine development. Vaccination in fish is complicated by their
      aquatic environment. Individual injections are labor-intensive and stressful,
      since fish have to be removed from the water and anaesthetized. Some vaccines
      offer a limited duration of protection, and thus booster applications are
      required. In salmonid species, many commercial vaccines use oil-based adjuvants,
      resulting in a greatly improved duration of protection. However, oil-based
      adjuvants have been related to significant growth depression, internal adhesions
      and injection site melanization, resulting in carcass downgrading. Oral
      administration to aquatic species is by far the most appealing method of vaccine
      delivery: there is no handling of the fish, which reduces stress; and
      administration is easy and suitable for mass immunization. However, few oral
      vaccines have been commercialized, due in part to the increased quantity of
      antigen required to provoke an immune response, and the lack of an adequate
      duration of protection. For effective oral delivery, protective antigens must
      avoid digestive hydrolysis and be taken up in the hindgut in order to induce an
      effective protective immune response. Antigen encapsulation technologies have
      been used to protect antigen; however, such strategies can be expensive and are
      not always effective. Alternative approaches, currently under development, are
      discussed.

PMID- 15984343
TI  - Efficacy and safety of a feline immunodeficiency virus vaccine.
AB  - Fel-O-Vax FIV is an inactivated virus vaccine designed as an aid in the
      prevention of infection of cats, 8 weeks or older, by feline immunodeficiency
      virus (FIV). It contains two genetically distinct FIV strains. The efficacy of
      this vaccine was demonstrated in a vaccination-challenge study designed to meet
      various regulatory requirements for registering the vaccine. Eight-week-old
      kittens were vaccinated with an immunogenicity vaccine which contained minimal
      release levels of FIV antigens formulated with a proprietary adjuvant system.
      Twelve months later, all vaccinates and controls were challenged with a
      heterologous FIV strain. Following the vigorous challenge exposure, cats were
      monitored for FIV viremia. It was found that 16% of the vaccinated cats developed
      viremia while 90% of the controls became persistently infected with FIV, which
      demonstrated that the vaccine was efficacious and the protective immunity lasted
      for at least 12 months. The safety of the vaccine was demonstrated by a field
      safety trial in which only 22 mild reactions of short duration were observed
      following administering 2051 doses of two pre-licensing serials of Fel-O-Vax FIV
      to cats of various breeds, ages and vaccination histories. Thus, Fel-O-Vax FIV is
      safe and efficacious for the prevention of FIV infection in cats.

PMID- 15984345
TI  - Warmwater fish vaccinology in catfish production.
AB  - The ability of the fish industry to provide a continuous supply of fish protein
      depends on both proper biosecurity and strategies to significantly reduce the
      risk of infectious diseases. Vaccination is a safe and effective means to prevent
      disease and to increase the productivity and profitability of farmed fish.
      Vaccines are likely to be the prime prophylactic measure of the future because of
      rapidly developing advances in fish vaccine technology and producer acceptance.
      The efficacy of a vaccine is influenced by a variety of factors that must be
      considered in the development of vaccination strategies for fish. This review
      highlights some of these factors. The response to a modified live vaccine against
      Edwardsiella ictaluri is used for illustration.

PMID- 15984346
TI  - Recent trends in the molecular diagnosis of infectious bursal disease viruses.
AB  - Infectious bursal disease virus (IBDV) causes an immunosuppressive disease in
      young chickens. Two serotypes of this double-stranded RNA virus exist but only
      serotype 1 viruses cause disease in chickens. Detection and strain identification
      of IBDV is important because antigenic subtypes found within serotype 1 make it
      necessary to tailor vaccination programs to the antigenic type found in the
      bird's environment. Because conventional virus isolation and characterization are
      not practical for routine diagnosis of IBDV, antigen-capture enzyme-linked
      immunosorbent assay (ELISA) and molecular assays based on reverse transcription
      polymerase chain reaction (RT-PCR) technology were developed. Compared with
      antigen-capture ELISA, RT-PCR assays have greater versatility and are more
      sensitive and specific. Strain identification has been accomplished using a
      variety of post-RT-PCR assays, including restriction enzyme digestion of the RT
      PCR products. The resulting restriction fragment length polymorphisms (RFLP) are
      used to differentiate viruses into molecular groups that correlate with antigenic
      and pathogenic types. Recently, two types of real-time RT-PCR have been used to
      identify and differentiate strains of IBDV. Both methods use distance-dependent
      interaction between two dye molecules, known as fluorescence resonance energy
      transfer (FRET). The dye molecules are attached to one or more nucleotide probes
      that detect specific nucleotide sequences of the virus. Our laboratory has used a
      two-probe assay to identify single-nucleotide mutations among IBDV strains. A
      mutation probe is used in this assay to detect substitution mutations in a region
      of the viral genome that encodes a neutralizing epitope of the virus. These
      assays are accurate, reliable and inexpensive compared with conventional RT-PCR
      because they do not require RFLP or other labor-intensive post-RT-PCR assays to
      distinguish viral strains.

PMID- 15984347
TI  - Diagnosis of Mycoplasma hyopneumoniae.
AB  - Mycoplasma hyopneumoniae, the cause of enzootic pneumonia, remains an important
      pathogen in the swine industry. This small, complex organism colonizes the
      ciliated cells of the respiratory tract, resulting in little exposure to the
      immune system. Confirming the presence of M. hyopneumoniae, as well as
      identifying its role in respiratory disease and pneumonia, remains challenging to
      the veterinary profession. While culture of the organism remains the gold
      standard for identification, the use of serology, the polymerase chain reaction
      and various assays to detect the presence of M. hyopneumoniae in tissue is common
      in diagnostic laboratories. Because of the role M. hyopneumoniae plays in
      increasing the severity of pneumonia associated with concurrent bacterial and
      viral infections, understanding the pathogenesis and diagnostic assays available
      is critical for developing effective intervention strategies to control
      respiratory disease on a herd basis.

PMID- 15984348
TI  - The emergence of Clostridium difficile as a pathogen of food animals.
AB  - Clostridium difficile causes pseudomembranous colitis in humans, usually after
      disruption of the bowel flora by antibiotic therapy. Factors mediating the frank
      disease include the dose and toxigenicity of the colonizing strain, its ability
      to adhere to colonic epithelium, the concurrent presence of organisms that affect
      multiplication and toxin production or activity, and the susceptibility of the
      host. Toxins A (an enterotoxin) and B (a cytotoxin) play the major role in
      pathogenesis and the detection of toxins in gut contents is the gold standard for
      diagnosis. Disease in horses takes the form of often-fatal foal hemorrhagic
      enteritis. Nosocomial, antibiotic-associated, disease is increasingly common in
      adult horses. Enteric clinical signs are reported in ostriches, companion animals
      and recently calves. Clostridium difficile colitis is now a common diagnosis in
      neonatal pigs in the USA and elsewhere. Clinical features include onset at 1-5
      days of age, sometimes with dyspnea, mild abdominal distension and scrotal edema,
      and commonly with yellow, pasty diarrhea. There is mesocolonic edema grossly,
      with microscopic diffuse colitis, mucosal edema, crypt distension, epithelial
      necrosis and superficial mucosal erosion. Neutrophil infiltration of the lamina
      propria is common, and fibrin and numerous rod-shaped bacteria are observed on
      the surface. About two-thirds of litters and one-third of piglets will be
      affected (based upon positive toxin tests), although this appears to vary with
      the season. The case fatality rate is probably low if considering only direct
      effects of C. difficile infection. The significance of toxin-positive non
      diarrheic pigs and the nature of the interaction of toxins A and B with
      enterocytes are unknown. Given the widespread occurrence of the disease, there is
      substantial effort to develop immunoprophylactic products.

PMID- 15984350
TI  - Staffing your clinic.

PMID- 15984349
TI  - Feline immunodeficiency virus diagnosis after vaccination.
AB  - Prior to the widespread use of vaccination for the control of feline
      immunodeficiency virus (FIV) infection, diagnosis was made by the detection of
      antibodies against FIV. A number of commercial animal side tests perform quite
      well for this determination, with positive predictive values between 91 and 100%
      and negative predictive values between 96 and 100%. Furthermore, results of these
      tests could be confirmed by western blot analysis of FIV test-positive sera.
      Currently, a killed whole virus FIV vaccine has been made available to
      practitioners. Vaccinated cats seroconvert by ELISA and western blot, making
      presently available diagnostic tests, which rely on antibody detection, useless
      in cats after vaccination. The advisory panels of the American Association of
      Feline Practitioners and Academy of Feline Medicine both recommend testing for
      feline leukemia virus antigen and FIV antibody before vaccination.

PMID- 15984351
TI  - Six steps to startup success.

PMID- 15984352
TI  - Patient Information. Monitoring blood glucose: a how-to for kids.

PMID- 15984353
TI  - Clearing the way: treating venous thromboembolism and deep vein thrombosis.

PMID- 15984354
TI  - Fright of passage.

PMID- 15984355
TI  - Make your message work.

PMID- 15984356
TI  - Should you outsource?

PMID- 15984357
TI  - Ownership ups and downs.

PMID- 15984358
TI  - The forgotten component of postpartum assessment.

PMID- 15984359
TI  - Pain in the elderly.

PMID- 15984360
TI  - Nature's wrath? A closer look at complications with five popular herbs.

PMID- 15984361
TI  - Taming the little tigers. Golf-related head injuries in children.

PMID- 15984362
TI  - Ten tips for new NPs.

PMID- 15984363
TI  - Two decades of servicce. AANP celebrates 20 years as profession reaches 40.

PMID- 15984364
TI  - Saying goodbye.

PMID- 15984365
TI  - The future of dental practice.

PMID- 15984366
TI  - Esthetic considerations in implant dentistry.
AB  - The use of dental implants continues to increase world wide, and single tooth
      replacement has evolved into a predictable procedure which is rapidly becoming
      the preferred method of tooth replacement. Clearly, there is increased awareness
      of and demand for esthetics in traditional restorative dentistry as well as
      implant-related care. Predictable delivery of highly esthetic, naturally
      appearing implant restorations is dependent on a host of factors, some of which
      are hardware-based and some of which are related to the morphology and tissue
      quality of the proposed implant site. An organized approach to patient evaluation
      and treatment planning by the implant treatment team will improve recognition of
      these factors of esthetic significance and will facilitate the development of
      strategies to achieve esthetic excellence on a more predictable basis.

PMID- 15984367
TI  - Cone beam CT: a new tool for esthetic implant planning.

PMID- 15984368
TI  - Practical incorporation of computed tomography into daily implant treatment
      planning.

PMID- 15984369
TI  - Esthetic implant restorations.

PMID- 15984370
TI  - Digital laser scans used in morphometric analysis of human skulls to demonstrate
      dental occlusal function--part I.

PMID- 15984371
TI  - Ethical dilemma #51. "Dealing with uncertainty: bisphosphonate-related
      osteonecrosis".

PMID- 15984372
TI  - Oral and maxillofacial pathology case of the month. Histoplasmosis.

PMID- 15984373
TI  - The roadmap to guide patients from diagnosis to acceptance.

PMID- 15984374
TI  - Diagnosing pertussis: the role of polymerase chain reaction.
AB  - BACKGROUND: Whereas the diagnosis of classical pertussis has traditionally been
      based on clinical criteria, increasing numbers of atypical presentations suggest
      the need for an extensive laboratory-based approach. OBJECTIVES: To assess the
      relative efficacy of clinical and laboratory methods in the diagnosis of
      Bordetella pertussis by patient age and immunization status. METHODS: We compared
      the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78
      recently vaccinated, and 75 post-vaccinated children with suspected pertussis.
      Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase
      chain reaction. RESULTS: PCR and culture identified 41% and 7% of patients with
      B. pertussis, respectively (P < 0.001). All positive cultures were PCR-positive.
      Positive PCR was less common among those recently vaccinated than among those in
      the pre- (P < 0.001) and post-vaccinated groups (P < 0.05). Positive culture was
      more common among those pre-vaccinated than among those recently vaccinated (P <
      0.01). Positive tests for immunoglobulin M and A were more common among the post
      vaccinated than the pre- and recently vaccinated (P < 0.001), respectively.
      Logistic regression analyses revealed that clinical criteria have no significant
      association with infection in recently and post-vaccinated children. Among the
      pre-vaccinated children, whoop and cough duration were associated with a positive
      PCR (odds ratio 7.66 and 0.5, P < 0.001). Seventy-six percent of pre-vaccinated,
      39% of recently vaccinated and 40% of post-vaccinated children with positive PCR
      did not meet the U.S. Centers for Disease Control diagnostic criteria for B.
      pertussis. CONCLUSIONS: PCR is a useful tool for pertussis diagnosis,
      particularly in pre-vaccinated infants. The yield of culture and serology is
      limited, especially among pre- and recently vaccinated children. In pre
      vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should
      be implemented promptly.

PMID- 15984375
TI  - Cardiovascular risk assessment and treatment to target low density lipoprotein
      levels in hospitalized ischemic heart disease patients: results of the HOLEM
      study.
AB  - BACKGROUND: Hypercholesterolemia control status is lacking throughout the western
      world. OBJECTIVES: To examine whether the treatment recommendations given to
      ischemic heart disease patients at hospital discharge are compatible with the
      guidelines of the Israeli medical societies and the U.S. National Cholesterol
      Education Program for coronary artery disease prevention; and to study the
      effects of brief educational sessions on the adherence of physicians with the
      guidelines. METHODS: We included consecutive IHD patients admitted to four
      central hospitals in Israel between 1998 and 2000. The study was conducted in two
      phases. In phase 1, we reviewed discharge letters to document treatment
      recommendations given to each patient. In phase 2 we educated the practitioners
      by reviewing the Israeli medical societies and the NCEP guidelines and the
      quality of their recommendations in phase 1, after which we reevaluated the
      discharge letters. RESULTS: The study included 2,994 patients: 627 in phase 1 and
      2,367 in phase 2. Of the patients who needed cholesterol-lowering according to
      their low density lipoprotein levels, 37.4% were not prescribed such drugs at
      discharge (under-treatment group). This proportion was reduced by education to
      26.6% (P < 0.001) in phase 2. Of the treated patients, 65.6% did not reach the
      target LDLgoal in phase 1 (under-dosage group) as compared to 60.2% in phase 2 (P
      = 0.23). In phase 2 there was an increase in the percent of patients reaching LDL
      levels <130 mg/day (69.3% vs. 63.8% of patients prescribed medication, P = 0.01),
      but the percent of patients reaching' LDL levels <100 was not different in phase
      2 after adjusting for age and gender (the odds ratio for reaching target LDL was
      1.16, with 95% confidence interval of 0.95-1.43). CONCLUSIONS: Physician
      recommendations to IHD patients discharged from hospital were suboptimal. We
      documented a high proportion of under-treated and under-dosaged patients. Brief
      educational sessions have a beneficial effect on the usage of statins; however,
      additional effort in guideline implementations is needed.

PMID- 15984376
TI  - Association of high body mass index with low age of disease onset among Arab
      women with type 2 diabetes in a primary care clinic.
AB  - BACKGROUND: Type 2 diabetes is usually associated with obesity, and both
      conditions are frequently detected in the Arab population in Israel. Recent
      studies have demonstrated that diabetes can be prevented by a change in
      lifestyle. OBJECTIVE: To assess the prevalence of diabetes in an Arab community,
      the contribution of obesity to diabetes development, and the therapeutic
      potential of a preventive program. METHODS: Data were obtained from the medical
      files of diagnosed diabetes patients attending a primary care clinic in an Arab
      village in northern Israel. RESULTS: Type 2 diabetes was diagnosed in 323
      patients of whom 63% were women. The prevalence of diabetes below age 65 years
      was significantly higher among women than men. Diabetic women were younger than
      men at diagnosis (48.27 vs. 59.52 years respectively) and were found to have
      higher body mass index (34.35 vs. 30.04 respectively) at diagnosis. The age at
      diagnosis of diabetes was strongly correlated with BMI (r = 0.97, P < 0.0001).
      CONCLUSIONS: Women of Arab origin are at higher risk of developing type 2
      diabetes compared to men. Obesity in women seems to be associated with higher
      diabetes risk as well as earlier appearance of the disease. Therefore, they will
      have the disease for longer and, consequently, will be at higher risk for
      complications.

PMID- 15984377
TI  - Malaria in travelers returning from short organized tours to holiday resorts in
      Mombassa, Kenya.
AB  - BACKGROUND: Short trips to holiday resorts in Mombassa, Kenya, have gained
      popularity among Israelis since the early 1990s. A cluster of cases of malaria
      among returned travelers raised concern that preventive measures were being
      neglected. OBJECTIVES: To characterize the demographic and clinical features of
      malaria acquired in Kenya, and to assess the adequacy of preventive measures.
      METHODS: Data were collected from investigation forms at the Ministry of Health.
      All persons who acquired malaria in Kenya during the years 1999-2001 were
      contacted by phone and questioned about use of chemoprophylaxis, attitudes
      towards malaria prevention, and disease course. Further information was extracted
      from hospital records. RESULTS: Kenya accounted for 30 (18%) of 169 cases of
      malaria imported to Israel and was the leading source of malaria in the study
      period. Of 30 malaria cases imported from Kenya, 29 occurred after short (1-2
      weeks) travel to holiday resorts in Mombassa. Average patient age was 43 +/- 12
      years, which is older than average for travelers to tropical countries. Only 10%
      of the patients were fully compliant with malaria chemoprophylaxis. The most
      common reason for non-compliance was the belief that a short trip to a holiday
      resort carries a negligible risk of malaria. Only 3 of 13 patients (23%) who
      consulted their primary physician about post-travel fever were correctly
      diagnosed with malaria. Twenty percent of cases were severe enough to warrant
      admission to an intensive care unit; one case was fatal. CONCLUSIONS: Measures
      aimed at preventing malaria and its severe sequelae among travelers should
      concentrate on increasing awareness of risks and compliance with malaria
      chemoprophylaxis.

PMID- 15984378
TI  - Complications of circumcision in Israel: a one year multicenter survey.
AB  - BACKGROUND: In Israel, virtually all children undergo circumcision in the
      neonatal period. Traditionally, it is commonly performed by a "Mohel" (ritual
      circumciser) but lately there is an increasing tendency among the educated
      secular population to prefer a medical procedure performed by a physician and
      with local anesthetic injection. OBJECTIVES: To evaluate the outcome of this
      procedure and to compare the complication rate following circumcisions performed
      by ritual circumcisers and by physicians. METHODS: In 2001, of the 19,478 males
      born in four major medical centers in Israel 66 had circumcision-related
      complications. All the children were circumcised in non-medical settings within
      the community. The patients were medically evaluated either urgently due to
      immediate complications or electively in outpatient clinics later on. Upon the
      initial assessment a detailed questionnaire was filled to obtain data regarding
      the procedure, the performer, and the subsequent complications. RESULTS: All the
      circumcisions were performed during the early neonatal period, usually on day 8
      of life (according to Jewish law). in 55 cases (83%) it was part of a ritual
      ceremony conducted by a ritual circumciser (Mohel), while in 11 babies (17%)
      physicians were involved. Acute bleeding after circumcision was encountered in 16
      cases (24%), which required suturing in 8. In addition, we found two cases of
      wound infection and one case of partial amputation of glans penis in which the
      circumcision was performed by a ritual circumciser. Among the late complications,
      the most common was excess of skin in 38 cases (57%); 5 children (7.5%) had
      penile torsion and 4 children (6%) had shortages of skin, phimosis and inclusion
      cyst. The overall estimated complication rate of circumcision was 0.34%.
      CONCLUSIONS: Complications of circumcision are rare in Israel and in most cases
      are mild and correctable. There appears to be no significant difference in the
      type of complications between medical and ritual circumcisions.

PMID- 15984379
TI  - Accuracy and consistency of fine-needle aspiration biopsy in the diagnosis and
      management of solitary thyroid nodules.
AB  - BACKGROUND: Fine-needle aspiration biopsy has been well established as a
      diagnostic technique for selecting patients with thyroid nodules for surgical
      treatment, thereby reducing the number of unnecessary surgical procedures in
      cases of non-malignant tumors. OBJECTIVES: To evaluate the sensitivity,
      specificity, accuracy, and positive and negative predictive values of FNAB in
      cases of a solitary thyroid nodule. METHODS: The preoperative FNAB results in 170
      patients who underwent thyroidectomy due to a solitary thyroid nodule were
      compared retrospectively with the final postoperative pathologic diagnoses.
      RESULTS: In cases of a solitary thyroid nodule, FNAB had a sensitivity of 79%,
      specificity of 98.5%, accuracy of 87%, and positive and negative predictive
      values of 98.75% and 76.6% respectively. All cases of papillary carcinoma
      diagnosed by FNAB proved to be malignant on final histology, while 8 of 27 cases
      of follicular adenoma detected by preoperative FNAB were shown to be malignant on
      final evaluation of the surgical specimen. CONCLUSIONS: FNAB cytology reduces the
      incidence of thyroidectomy since this method has excellent specificity and
      sensitivity and a low rate of false-negative results. It proved to be cost
      effective and is recommended as the first tool in the diagnostic workup in
      patients with thyroid nodules.

PMID- 15984380
TI  - Anglographic functional characterization of the coronary sinus.
AB  - BACKGROUND: Coronary sinus is a venous conduit with dynamic and unclear function
      with regard to coronary circulation. OBJECTIVES: To describe the dynamic changes
      of the coronary sinus during the cardiac cycle. METHODS: The angiographic feature
      of the coronary sinus was evaluated in 30 patients undergoing diagnostic and
      therapeutic coronary angiography. RESULTS: Prolonged angiographic imaging
      following coronary injections permitted accurate demonstration of the coronary
      sinus in all 30 patients. We report, for the first time, that the coronary sinus
      can be divided into two angiographic functional/anatomic portions, upper and
      lower. The lower part is prone to a highly dynamic contraction/relaxation
      pattern, observed in 12 of the 30 patients, while 10 patients had normal and 8
      had low contractile pattern on angiography. Clinical assessment of these patients
      did not identify an association with this motion pattern. CONCLUSIONS: The
      coronary sinus is an important anatomic/functional structure that should be
      further investigated in patients with various forms of heart disease.

PMID- 15984381
TI  - Treatment of rectal cancer by chemoradiation followed by surgery: analysis and
      early clinical outcome in 66 patients.
AB  - BACKGROUND: Abdominoperineal resection entails the need for a permanent
      colostomy, which significantly reduces patient self-image and quality of life.
      OBJECTIVE: To investigate the effectiveness of preoperative chemoradiation in
      increasing the resectability rates of rectal cancer and increasing the anal
      sphincter preservation rate. METHODS: The study group included 66 patients aged
      33-84 years with T2-T3 rectal carcinoma who were treated in our institute from
      1997 to 2002 with preoperative chemoradiation followed by surgery 6 weeks later.
      All patients underwent preoperative transrectal endoscopic ultrasound for tumor
      staging and localization. The duration of follow-up was 25 months. RESULTS:
      Chemoradiation led to tumor downstaging in 61 patients (92.4%), all of whom
      underwent low anterior resection. Only 11.4% of this group needed a temporary (6
      weeks) loop colostomy/ileostomy. None of the 16 patients with post-treatment T0
      tumors had evidence of malignant cells on pathologic study. Five patients (7.6%)
      failed to respond to chemoradiation and underwent APR. There were no major
      complications, such as leakage, and no deaths. CONCLUSIONS: Neoadjuvant
      chemoradiation is an effective modality to downstage advanced rectal cancer,
      improving patient quality of life by significantly reducing the need for a
      terminal permanent colostomy, or even a temporary one.

PMID- 15984382
TI  - Seasonality of month of birth of children and adolescents with type 1 diabetes
      mellitus in homogenous and heterogeneous populations.
AB  - BACKGROUND: Type 1 childhood-onset diabetes mellitus has a multifactorial origin
      involving an interplay between genetic and environmental factors. We have
      previously shown that many children who subsequently develop T1DM have a
      different seasonality of birth than the total live births of the same population,
      supporting the hypothesis that perinatal viral infection is a trigger for the
      autoimmune process of T1DM. OBJECTIVES: To compare the seasonality of children
      with T1DM in different populations around the world for which data were
      available. METHODS: We analyzed large cohorts of T1DM patients with a clinical
      disease onset before age 14 or 18 years. RESULTS: We found a seasonality pattern
      only in ethnically homogenous populations (such as Ashkenazi Jews, Israeli Arabs,
      individuals in Sardinia and Canterbury, New Zealand, and Afro-Americans) but not
      in heterogeneous populations (such as in Sydney, Pittsburgh and Denver).
      CONCLUSIONS: Our findings attempt to explain the controversial data in the
      literature by showing that ethnically heterogeneous populations comprising a
      mixture of patients with various genetic backgrounds and environmental exposures
      mask the different seasonality pattern of month of birth that many children with
      diabetes present when compared to the general population.

PMID- 15984383
TI  - Inflammatory abdominal aortic aneurysms.

PMID- 15984384
TI  - Renin-angiotensin system inhibitors and atrial fibrillation.

PMID- 15984385
TI  - Genetic ideology of dilated cardiompathy.
AB  - Familial cardiomyopathies represent a substantial portion of idiopathic dilated
      cardiomyopathy in clinical practice. Diversity of clinical presentations and
      variability in penetrance lead to under-recognition of this disease entity as an
      inherited disorder. The mechanisms by which mutations in different genes perturb
      cardiac function and lead to pathologic remodeling help us understand the
      molecular pathways in disease pathogenesis and define the potential targets for
      therapeutic interventions. Appreciating when DCM is inherited might spare
      unnecessary diagnostic efforts and, instead, help give appropriate attention to
      the timely detection of subclinically affected family members. Establishing
      preventive therapy in asymptomatic family members showing early signs of cardiac
      dysfunction might prevent death and slow down progression to end-stage heart
      failure.

PMID- 15984386
TI  - New vaccines--new dilemmas.

PMID- 15984387
TI  - Secondary prevention of ischemic heart disease: closing the gap.

PMID- 15984388
TI  - Complex impact of obesity on type 2 diabetes.

PMID- 15984389
TI  - Malaria--a disease that refuses to die but continues to kill.

PMID- 15984390
TI  - Carotid artery dissection after scuba diving.

PMID- 15984391
TI  - Intravenous prostacyclin in the treatment of persistent pulmonary hypertension of
      the newborn refractory to inhaled nitric oxide.

PMID- 15984392
TI  - Renal artery pseudoaneurysm after partial nephrectomy complicated by rupture into
      the collecting system, managed by selective angiographic embolization.

PMID- 15984393
TI  - Capsule endoscopy diagnosis of celiac disease and ileal tumors in a patient with
      melena of obscure origin.

PMID- 15984395
TI  - The issue of oral medications and a fecal ostomy.

PMID- 15984396
TI  - Negative pressure wound therapy pumps and ostomy supplies.

PMID- 15984397
TI  - Randomized crossover comparison of adhesively coupled colostomy pouching systems.
AB  - Ostomy pouching systems affect well being and quality of life, making selection
      of the appropriate system a key element of ostomy care. Several innovative
      adhesively coupled, two-piece systems are on the market. They feature flexible
      low profiles, allowing pouch removal/replacement without changing the skin
      barrier or wafer. This facilitates inspection or pouch changes without disrupting
      peristomal skin. Because few controlled trials compare pouching system
      effectiveness, a prospective, randomized open-label, crossover study was
      conducted. Under the supervision of ostomy care nurses in six outpatient clinics
      in Germany, clinical performance of and patient preferences for two adhesively
      coupled, closed-end pouching systems were compared during normal use. One is a
      gelatin/pectin-based skin barrier sealed to the pouch with a company-specific
      adhesive coupling technology (System E); the other, a grooved base plate wafer
      adhesive pouch coupling system (System F). Seventeen attributes and seven end-of
      study measures that included comfort, flexibility, wear time, ease of removal,
      and overall performance were assessed. Informed, consenting participants were
      randomly assigned to use one system for five skin barrier/wafer changes or up to
      15 days and subsequently switched to the alternative system for a similar period.
      The 39 participants used a total of 1,645 pouches and 342 skin barriers. All were
      found safe as determined by incidence and nature of the reported peristomal skin
      problems, subject withdrawals, and adverse events for both systems. However,
      System E provided longer pouch wear times (P < 0.01). End-phase ratings favored
      System E on 10 of the 17 attributes (P < 0.04) and System Fon none. More
      participants preferred System E on all seven end-of-study measures, five
      significantly (comfort, flexibility, wear time, ease of removal, and overall
      performance; (P < 0.02). These participant-reported, ostomy-related outcomes
      underscore the importance of product evaluation and selection for persons with an
      ostomy.

PMID- 15984398
TI  - Negative pressure wound therapy: "a rose by any other name".
AB  - Negative pressure wound therapy is one of the dominant adjunctive wound care
      modalities used in North America. One company has a proprietary hold on the
      market for this type of wound therapy and recent wound care literature has
      focused on the company's products rather than on the concept itself. Currently
      utilized standards for negative pressure wound therapy are based on a few
      relatively recent publications originating after 1997. However, a review of the
      English and Russian literature that predates this work reveals discrepancies
      regarding optimal duration of treatment, intensity of negative pressure, mode of
      application, timing of application, and intervals between treatments. A careful
      review of research that has rarely been cited in recent wound care literature
      elucidates the inconsistencies between currently held dogma and less well known
      negative pressure research. In order to achieve optimal outcomes of care, current
      practices must be re-evaluated and researched using well-established guidelines
      for determining treatment safety and effectiveness.

PMID- 15984399
TI  - Patient perceptions and provider documentation of diabetes care in rural areas.
AB  - Measures of effective diabetes management usually include laboratory results and
      the provider's point of view, omitting the patient perspective. To address this
      oversight, a descriptive study was conducted to examine congruence between rural
      patient self-reported and provider-documented information on American Diabetes
      Association recommended guidelines. Provider medical record information and
      patient questionnaires were matched for 149 patients with a diagnosis of type 2
      diabetes being treated at rural healthcare facilities. Chi-squared testing showed
      a significant difference (P < 0.05) between patient and provider information in
      answers to questions on blood pressure and cholesterol testing, eye examination,
      influenza and pneumovax rates, and diabetic and nutrition education. Patients'
      perception of diabetes and blood pressure control did not always match documented
      values. To achieve diabetes control, providers must implement clinical practice
      guidelines and patients must take an active role in their disease management.
      Both must communicate effectively. This does not seem to be the case in rural
      areas.

PMID- 15984400
TI  - Brown recluse spider bites: a complex problem wound. A brief review and case
      study.
AB  - Brown recluse spiders (Loxosceles reclusa) are responsible for virtually all
      documented cases of spider bites leading to significant necrosis. The actual
      spider bite often goes unnoticed for as long as 4 to 6 hours, which makes
      diagnosis and, therefore, appropriate treatment, difficult. The spider bite
      generally results in either a necrotic wound or systemic symptoms that can lead
      to hemolysis. The patient described in this article experienced both
      complications. Dapsone and hyperbaric oxygen therapy brought the adverse response
      to the bite under control. The patient was hospitalized for 7 days during
      treatment for hemolysis and an extensive, necrotic wound. Efforts are underway to
      develop an assay to provide a definitive diagnosis for the brown recluse spider
      bite, but none is yet commercially available. Antivenom is scarce; capture of the
      offending spider appears to be most helpful in the diagnosis and proper treatment
      of spider bites.

PMID- 15984401
TI  - [Endovascular treatment of unruptured middle cerebral artery aneurysms].
AB  - INTRODUCTION: Middle cerebral artery aneurysms (MCA) often present an unusual
      anatomical feature for the endovascular treatment and are frequently sent to
      surgery. We report our experience in the endovascular treatment of unruptured MCA
      aneurysms and compare it with results from the neurosurgical literature. PATIENTS
      AND METHODS: In this retrospective study were included all patients with
      unruptured MCA aneurysms treated in our institution between November 1998 and
      December 2003. 3D imaging was performed in all cases to determine precisely the
      relationship between aneurysm and parent artery. The degree of occlusion of the
      aneurysms was estimated according to Raymond's classification. The neurological
      state was evaluated according to the Rankin scale and was re-evaluated at the
      time of each follow-up. RESULTS: Eighty four patients with 100 aneurysms were
      analysed. Ninety aneurysms were treated by endovascular approach. Nine aneurysms
      were sent to surgery, after 3D imaging analyses or failed endovascular treatment.
      In one patient, related to the aneurysm configuration, a conservative attitude
      has been adopted. Four giant aneurysms were treated by parent vessel occlusion
      and 86 aneurysms were selectively occluded. The remodelling technique with
      balloon was performed in 58.1% of cases. Eight patients presented a new
      neurological deficit. The deficit was transient in six cases, and permanent in 2
      cases. There was no mortality in this series. In 86 aneurysms selectively
      treated, there were 87.2% good results (grades A and B). Seventy one aneurysms
      (82.5%) treated were controlled between 3 and 58 months with a 19.6 months
      average. Recurrences were observed in 25.3% of cases. They were major in 9.8% and
      retreatment was performed. CONCLUSION: We report the feasibility of the
      endovascular treatment of MCA aneurysms previously estimated untreatable. Per
      procedural 3D imaging and remodelling technique were fundamental tools in the
      management of these aneurysms.

PMID- 15984402
TI  - Angioplasty and stenting of the cervical carotid bifurcation under filter
      protection: a prospective study in a series of 53 patients.
AB  - The aim of this study is to assess safety, reliability, ease of use and
      usefulness of filter protection devices during angioplasty and stenting of
      stenotic lesions of the cervical carotid bifurcation. Over a period of 42 months,
      53 patients harboring a cervical carotid bifurcation stenotic lesion were
      treated, by angioplasty and/or stenting using filter protection devices of
      different kinds. The stenosis was atherosclerotic in 48 cases, post-surgical in
      four and post-radiation in one case. In all cases, the treatment was successful,
      with good restoration of the luminal diameter. There were three major strokes
      (5.6%) and one minor stroke (1.9%). Two of these (one major, one minor) occurred
      a few hours after the stenting procedure and both seemed by all evidence due to a
      hemorrhagic hyperperfusion syndrome. One hemiparesis and dysphasia occurred two
      days after the procedure, secondary to subacute thrombosis with occlusion of the
      stent. One patient complained of three episodes of decrease in visual acuity of
      the eye ipsilateral to the stenting in the two weeks following treatment. In
      conclusion, in our experience, use of the devices adds only few minutes to the
      procedure time; direct lesions of the arterial wall, such as dissections or
      intraluminal thrombi, related to the use of filters were never observed, and
      spasm of the distal I.C.A. also proved rapidly regressive. The content of all
      filters, if any, was histologically examined, but plaque material was found only
      in one case, probably owing to our primary stenting technique without use of pre
      dilation. The major technical drawback is in-filter coagulation, which occurred
      in 16 cases, occluding the membrane of the filter and thus slowing or blocking
      intracranial flow. Such an event can be counteracted by a more aggressive anti
      coagulation protocol, which could, however, be responsible for the two
      complications with hemorrhagic brain infarction. Furthermore, we observed two
      other major neurological events, which bring the incidence of neurological
      complications in this series as high as 7.5%. Therefore, it is our opinion that
      safety of filters is not yet proven, and consequently great care must be taken in
      their use.

PMID- 15984403
TI  - [Quantitative relationships between ADC and perfusion changes in acute ischemic
      stroke using combined diffusion-weighted imaging and perfusion MR (DWI/PMR)].
AB  - MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the
      standard imaging technique to assess the individual brain pathophysiological
      status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than
      DWI abnormality is thought to reflect the presence of tissue at-risk of
      infarction, i.e., penumbra. However, there has been no detailed study of the
      quantitative relationships between perfusion and diffusion changes in stroke
      patients. According to the experimental concept of penumbra, the ADC would be
      expected to remain unchanged despite decreasing perfusion until a critical
      threshold is reached. We have tested this hypothesis directly in man. METHODS:
      DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs
      from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs
      were positioned within the ADC lesion (D), the mismatch area (M), and the normal
      appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected
      ratios for ADC and rCBF were computed for each ROI. RESULTS: The mean (+/-1 SD)
      ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N,
      respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and
      0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but
      not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A
      threshold for decline in ADC was apparent around 0.50 rCBF ratio. COMMENT: These
      results directly document in man that the ADC declines only after hypoperfusion
      has reached a certain degree (about 50%), consistent with the concept of the
      ischaemic penumbra.

PMID- 15984404
TI  - MR imaging features of idiopathic thoracic spinal cord herniations using combined
      3D-fiesta and 2D-PC Cine techniques.
AB  - Idiopathic thoracic spinal cord herniation (TISCH) is a rare cause of surgically
      treatable progressive myelopathy. The authors report 3 cases of TISCH diagnosed
      based on conventional T1- and T2-weighted Spin-Echo (SE) MR images in one case,
      and T1- and T2-weighted SE images combined with 3D-FIESTA (Fast Imaging Employing
      Steady state Acquisition) and 2D-Phase-Contrast Cine MR imaging in 2 cases.
      Conventional MRI findings usually provided the diagnosis. 3D-FIESTA images
      confirmed it, showing the herniated cord in the ventral epidural space. Moreover,
      in combination with 2D-Phase Contrast cine technique, it was a sensitive method
      to for the detection of associated pre- or postoperative cerebrospinal fluid
      spaces abnormalities.

PMID- 15984405
TI  - [Correlation between cranial vault size and brain size over time: preliminary MRI
      evaluation].
AB  - OBJECTIVES: To correlate changes of cranial vault measurements of an adult
      population during the aging process with brain size using the maximum width of
      the third ventricle in the axial AC-PC plane. MATERIALS AND METHODS: Prospective
      study of 126 adult subjects (range: 20 to 80 years) with normal brain MRI and
      without history of neuropsychiatric disorder. MEASUREMENTS INCLUDED: Cranial
      vault (Maximum length: Glabella-Opisthocranion, Maximum width: euryon-euryon, and
      maximum height: Basion-Vertex) measurements and maximum width of the third
      ventricle in the A C-PC plane. RESULTS: Vault measurements (length, width, high)
      were similar for every age group, irrespective of gender. The variability of
      cranial vault measurements between individuals was low (<1 cm). Cranial vault
      measurements were larger for men, but this was not significant when adjusted for
      body height Comparatively, a gradual widening of the third ventricle, with an
      exponential behavior, was observed with advancing age. CONCLUSION: Our results
      indicate that cranial vault measurements are stable over time (between 20-80
      years) comparatively to brain atrophy with advancing age. The low variability of
      cranial vault measurements and their stability over time should be taken into
      account during segmentation and normalization of brain parenchymal structures.

PMID- 15984406
TI  - Merkel cell tumor: report of two cases and review of the literature.
AB  - The "Merkel cell carcinoma" is a rare tumor usually occuring in the sun-exposed
      skin. Its poor prognosis is explained by a high rate of metastasis (one third of
      the patients at the initial presentation) and a high post-operative recurrence
      rate. Descriptions of the imaging features of this type of tumor are rare. We
      present two cases of Merkel cell carcinoma localized to the head region. In the
      first patient, the lesion involved the soft tissues of the scalp with secondary
      invasion of the skull and meninges. The second patient had a metastasis to the
      parietal lobe.

PMID- 15984407
TI  - The past, present, and future of bone morphometry: its contribution to an
      improved understanding of bone biology.
AB  - It was not until the 1950s that a better paradigm for bone biology evolved, which
      led to the birth of bone histomorphometry. Two clinicians, Harold Frost (1958
      1964) and Lent Johnson (1964), were responsible for the paradigm stating that the
      primary function of bone is mechanical load bearing with subsidiary function to
      participate in plasma calcium homeostasis to support hematopoesis. Dynamic bone
      histomorphometry was born when Milch et al. (1958) discovered bone localization
      of tetracycline and Frost generated the methodology to study tetracycline-based
      dynamic histological analysis of cortical bone remodeling (1961-1965). Dynamic
      bone histomorphometry did not blossom until Frost, while a Sun Valley Workshop
      participant, developed it to address trabecular bone dynamics. The combination of
      Arnold (1948) producing thin sections of plastic-embedded undecalcified bone and
      Frost's (1977-1983) modification of dynamic cortical bone histology for
      cancellous bone made it possible to study tetracycline-based dynamic
      histomorphometry of cancellous bone. It led to the better understanding of basic
      metabolic unit (BMU) remodelling and to Frost's mechanostat hypothesis, and
      characterized the rat model to accelerate the development of several drugs in the
      treatment of bone diseases. Currently, dynamic bone histomorphometry has
      contributed to studies in bone's mechanical usage windows, mechanical usage
      setpoint hypothesis, muscle-bone relations, marrow-bone relations, the Utah
      paradigm of musculoskeletal physiology, apoptosis, genetics (transgenic mice) and
      bone structure, bone quality, the lacunocanalicular network and bone modelling,
      and remodeling hypothesis, osteocyte role as mechanosensory, chemosensory, and
      regulatory in bone maintenance, targeted and untargeted remodeling, the role of
      permissive agents, etc., items in bone biology expounded briefly by Lent Johnson
      (1965) and continuously by Harold Frost at the Sun Valley Workshop (1965-2003).
      Finally, "What's next?" covers how to improve and perpetuate the employing of
      qualitative histomorphometry in research opportunities in hard tissue research.

PMID- 15984408
TI  - Roles for NF-kappaB and c-Fos in osteoclasts.
AB  - NF-kappaB and c-Fos are transcription factors that are activated in immune cells
      and in most other cell types following stimulation by a variety of factors,
      including cytokines, growth factors, and hormones. They regulate the expression
      of a large number of genes, and both are activated in osteoclast precursors after
      RANKL, IL-1, or TNF bind to their respective receptors. However, of these
      cytokines, only RANKL is required for the induction of osteoclast formation in
      vivo. Nevertheless, it is likely that IL-1, TNF, and other cytokines participate
      in the upregulation of osteoclast formation seen in a variety of conditions that
      affect the skeleton in which cytokine production is increased, including estrogen
      deficiency and inflammatory bone diseases. In this review, the RANKL/ OPG/RANK
      system and roles for NF-kappaB and c-Fos in osteoclasts are reviewed along with
      our current understanding of how this system may be disrupted in common bone
      diseases, such as postmenopausal osteoporosis, inflammatory arthritis, and
      Paget's disease.

PMID- 15984409
TI  - Mechanisms by which exercise improves bone strength.
AB  - Certain exercises can induce osteogenesis and improve bone strength, yet the
      biological processes involved in bone mechanotransduction are only beginning to
      be understood. Several pathways are emerging from current research, including
      calcium signaling associated with membrane ion channels, adenosine triphosphate
      signaling, second messengers such as prostaglandins and nitric oxide, and
      signaling involving mitogen-activated protein kinase. One characteristic of the
      mechanosensing apparatus that has only recently been studied is the important
      role of desensitization. Experimental protocols that insert "rest" periods to
      reduce the effects of desensitization can double anabolic responses to mechanical
      loading. Exercises that reduce desensitization may provide an effective means to
      build bone strength.

PMID- 15984411
TI  - Novel experimental effects on bone material properties and the pre- and postyield
      behavior of bones may be independent of bone mineralization.
AB  - In this article, we summarize the results of six different
      tomographic/biomechanical rat studies involving hypophysectomy (Hx), ovariectomy,
      treatment with rhGH, olpadronate, alendronate, and toxic doses of aluminum and
      the development of a genetic diabetes in the eSS strain. All these conditions
      induced some interesting and rarely reported effects on postyield bone strength.
      These effects were generally related neither to the degree of mineralization or
      the elastic modulus of the bone tissue nor to the preyield behavior of the bones.
      In two particular cases (Hx, eSS), the elastic modulus of bone tissue varied
      independently of its degree of mineralization. These results suggest the
      involvement of some microstructural factor(s) of bone tissue resistance to crack
      progression (a postyield feature of bone behavior), rather than to crack
      initiation (the yield-determining factor) in the corresponding mechanism. Changes
      in collagen or crystal structure may play that role. These changes are relevant
      to the mechanism of fracture production during plastic deformation, a feature of
      bone strength that might be independent from mineralization. Therefore, these
      changes might help to explain some effects of novel treatments on bone strength
      unrelated to bone mineralization. This questions the belief that the remaining
      bone mass in metabolic osteopenias is biologically and mechanically normal.

PMID- 15984412
TI  - The effects of suppressed bone remodeling by bisphosphonates on microdamage
      accumulation and degree of mineralization in the cortical bone of dog rib.
AB  - We evaluated the effects of suppressed bone remodeling caused by bisphosphonate
      on microdamage accumulation and degree of mineralization of bone (DMB) for the
      dog rib in two independent studies. Study 1: 36 female beagles, 1-2 years old,
      were treated daily for 1 year with saline vehicle, risedronate at 0.5 mg/kg/day,
      or alendronate at 1.0 mg/kg/day. Study 2: 29 beagles, 1 year old, were given
      lactose, or incadronate at 0.3 mg/kg/day or 0.6 mg/kg/day for 3 years. In both
      studies, the ninth rib was harvested. Intracortical remodeling was significantly
      suppressed following either 1 year or 3 years of bisphosphonate treatment without
      impairment of primary mineralization, although the remodeling rate was obviously
      lower in study 2 than in study 1 because of the aging of animals. Microdamage
      accumulation was significantly increased following any bisphosphonate treatment
      in response to the extent of remodeling suppression. One-year treatment with
      risedronate or alendronate did not significantly affect the mean DMB or osteonal
      distribution based on DMB. In contrast, mean DMB was significantly increased
      following 3 years of incadronate treatments, and osteonal distributions based on
      DMB showed a dose-dependent shift toward the higher values in incadronate-treated
      animals when compared with controls. Our results demonstrated that DMB was
      increased following only 3 years but not 1 year of bisphosphonate treatment. This
      finding suggests that suppressed remodeling induced by long-term bisphosphonate
      treatment increased DMB by increasing the population of old, highly mineralized
      osteons; however, the expression of this phenomenon depends on duration of the
      treatment because the secondary mineralization is a very slow process.

PMID- 15984410
TI  - Loading and bone fragility.
AB  - Data from retrospective and prospective observational and case-control studies
      suggest that activity is associated with reduced fracture risk, but consistently
      replicated bias may be responsible for this desired endpoint. Exercise during
      growth is likely to build a larger and stronger skeleton. However, cessation of
      exercise may erode the benefits. Modeling changes produced by exercise during
      growth may be permanent; remodeling changes may not be. Exercise during adulthood
      produces small increments in BMD or may prevent bone loss. Absence of evidence is
      not evidence of absence of effect, but the null hypothesis that exercise has no
      effect on fracture rates in old age cannot be rejected by any published data.
      Proof requires demonstration of a reduction in spine and hip fractures in well
      designed and well-executed prospective randomized studies; none exists. Blinded
      studies cannot be done, but open trials can and should be done.

PMID- 15984413
TI  - Histological evaluation for "bone quality" on two mouse models with different
      bone remodeling.

PMID- 15984414
TI  - Microdamage accumulation in the monkey vertebra does not occur when bone turnover
      is suppressed by 50% or less with estrogen or raloxifene.
AB  - Long-term suppression of bone turnover with alendronate has previously been shown
      to increase the degree of mineralization and accumulation of microdamage in
      animal bones. In an effort to ascertain if other suppressors of bone resorption
      can also affect mineralization and microdamage accumulation, we evaluated bones
      from cynomolgus macaques treated with raloxifene or conjugated equine estrogens
      (CEE). Cynomolgus monkeys (Macaca fascicularis) were randomized, ovariectomized
      (except for Sham controls), and orally treated each day for 2 years with vehicle
      (Sham and Ovx controls), 1 mg/kg raloxifene (R1), 5 mg/kg raloxifene (R5), or
      0.04 mg/kg CEE. The functional quality of the mineralized matrix was analyzed
      postnecropsy by biomechanical testing, histomorphometry, biochemistry, and
      nanoindentation. Failure testing of the whole vertebra showed no significant
      differences in vertebral strength among groups. Similarly, failure testing of a
      beam of pure bone that was machined from the femoral diaphysis also showed no
      differences in material strength (ultimate stress) between groups.
      Histomorphometry of the L2 centrum showed that Ovx tended to increase activation
      frequency relative to Sham controls. Estrogen (CEE) treatment for 2 years at
      about four times the clinical exposure tended to reduce activation frequency
      (Ac.f) by 41% compared to Ovx. Treatment with raloxifene at either approximately
      the clinical dose or five times higher nonsignificantly lowered Ac.f by 34% and
      23%, respectively, relative to Ovx. Raloxifene had similar effects on serum
      osteocalcin, a biochemical measure of systemic bone turnover. Analysis of
      microcrack surface density in the cancellous bone of L3 showed a 40% reduction
      for Ovx relative to Sham. CEE microcrack surface density was not different than
      Sham whereas the R5 crack density was significantly less than Sham and CEE. R1
      microcrack surface density was not significantly different from Sham or Ovx. No
      significant differences in crack length were observed among the groups. Hardness,
      which is a measure of the state of mineralization, and elastic modulus were
      measured for both trabecular bone on a micron scale by nanoindentation. No
      significant differences between groups were observed. In summary, differences in
      functional bone quality of the lumbar spine were not observed between Sham, Ovx,
      or treated monkeys. CEE increased microcracks from Ovx to Sham levels, whereas
      raloxifene had no effect on microdamage accumulation. We conclude that
      suppressing bone turnover by 40% or less offers protection against microdamage
      accumulation that could result in an increased risk of vertebral fracture.

PMID- 15984416
TI  - Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the
      osteopenic skeleton of ovariectomized rats.
AB  - The skeletal efficacy of raloxifene (Ral) plus weekly teriparatide [recombinant
      human parathyroid hormone (1-34), TPTD] combinations relative to each treatment
      alone or sequentially were evaluated in osteopenic, ovariectomized rats. In the
      first study, 6-month-old Sprague-Dawley rats were ovariectomized (Ovx) and
      permitted to lose bone for 1 month before treatment for the following 3 months.
      Raloxifene (Ral, 1 mg/kg/day orally) was evaluated alone and in combination with
      TPTD (10 or 30 microg/kg/week) administered weekly by subcutaneous injection.
      QCT, biomechanical testing, and histomorphometry were used to quantitate skeletal
      effects. Weekly TPTD alone at either dose had no skeletal effect relative to Ovx.
      Daily Ral prevented further loss of vertebral bone mineral density (BMD),
      resulting in BMD that was significantly greater than Ovx, but significantly less
      than age-matched, sham-Ovx, vehicle controls (sham). The raloxifene plus 30
      microg/kg/week TPTD group had vertebral BMD that was significantly greater than
      Ovx, Ral alone, and both TPTD dose-alone groups. Therefore, the Ral plus TPTD
      group completely restored bone mass to sham levels. Compression testing of lumbar
      vertebra L5 confirmed increased strength for both Ral plus TPTD combinations
      relative to Ovx, with strength not different from sham. Histomorphometry of the
      proximal tibial metaphysis showed that Ovx significantly increased eroded surface
      and bone formation compared to sham. Raloxifene treatment restored eroded surface
      and bone formation rate back to sham levels. Raloxifene plus TPTD at 30
      microg/kg/week resulted in a significantly higher mineral appositional rate
      compared to Ral and sham, which was not different from Ovx and TPTD alone.
      Raloxifene plus TPTD at both doses had eroded surfaces that were significantly
      less than Ovx but not different from sham or Ral alone. In a sequential study, 6
      month-old Ovx rats were permitted to develop osteopenia for 2 months before a
      daily TPTD 80 microg/kg/day subcutaneous injection was initiated. Following 2
      months of TPTD treatment, animals were either (1) continued on TPTD, (2)
      discontinued from TPTD, (3) switched to Ral 3 mg/kg/day, oral, or 17 alpha
      ethynyl estradiol (EE2) 0.1 mg/kg/day, oral, for another 2 months. Raloxifene and
      EE2 maintained most of TPTD-induced new bone in Ovx rats by preventing the
      increase in bone turnover rate after withdrawal of TPTD. Raloxifene also restored
      the elevated bone formation activity induced by TPTD to the level of sham. These
      data suggest that Ral and TPTD have complementary interactions in osteopenic, Ovx
      rats. Raloxifene inhibited bone resorption, and reduced high bone turnover
      without significantly retarding TPTD stimulation of bone formation activity.

PMID- 15984415
TI  - Phytoestrogen-rich herb formula "XLGB" prevents OVX-induced deterioration of
      musculoskeletal tissues at the hip in old rats.
AB  - This study investigated a phytoestrogen-rich herb formula, Xianlinggubao (XLGB)
      (including genistein 510 microg/g and daidzein 2500 microg/g), concerning
      prevention of OVX-induced deterioration of musculoskeletal tissues in 11-month
      old female Wistar rats, which were randomized into Sham, OVX, and XLGB groups.
      Daily oral administration of XLGB (250 mg/kg/day) started after OVX for 3 months.
      mRNA of MHC-I IIa IIb of abductor muscle was determined by RT-PCR. The proximal
      femoral BMD and geometry, microarchitecture, and mechanical strength were
      evaluated by pQCT, micro-CT, and compressive testing, respectively. The bone
      turnover biochemical markers serum osteocalcin (OC) and urinary deoxypyridinoline
      (DPD) were evaluated. The results showed that (1) XLGB-treated OVX rats showed no
      difference compared to the Sham group, whereas OVX induced significant
      deterioration in variables related to bone density, microarchitecture, and
      mechanical strength (P < 0.05); (2) biochemical markers showed no difference
      between sham and XLGB groups as compared with higher bone turnover in OVX rats (P
      < 0.05); (3) mRNA expression of MHC-I IIa IIb was downregulated in OVX rats but
      upregulated after XLGB treatment (P < 0.05); and (4) as compared with the OVX
      group, no uterine hypertrophy was found in XLGB-treated rats. In conclusion,
      findings of this study suggested that the herbal preparation XLGB was able to
      prevent OVX-induced deterioration of musculoskeletal tissues at the hip without
      causing uterine stimulation.

PMID- 15984417
TI  - Bone biopsy in various metabolic bone diseases studied by bone histomorphometry
      in China.

PMID- 15984418
TI  - Epidemiology of osteoporosis in mainland China.

PMID- 15984419
TI  - Epidemiology of hip fracture in Japan: incidence and risk factors.
AB  - Hip fracture is the most serious complication of osteoporosis and has been
      recognized as a major public health problem. The prevention of hip fractures is
      an high-priority issue because of the rapid increase of the number of elderly
      people in Japan. The General Research Committee for the Prevention and Treatment
      of Osteoporosis in Silver Health Science Researches sponsored by the Ministry of
      Health and Welfare (Director, Hajime Orimo) first undertook a nationwide survey
      of femoral neck fracture in 1987. This nationwide survey has been continued every
      5 years, in 1992, 1997, and 2002. The total number of new cases was nearly
      120,000 in the latest survey, and has been rising in every survey. Total number
      of new cases was about 1.4 times the baseline 1987 figures in 1992, 1.7 times in
      1997, and 2.2 times in 2002. The total number of new female patients was about
      three times higher than that of new male patients, a finding identical to those
      of the previous surveys. The incidences of hip fracture (per 10,000) according to
      sex and age was increased in both men and women, particularly among individuals
      80 years old or over. The Epidemiological Research Group on Osteoporosis,
      Ministry of Health and Welfare (Chairman; Hajime Orimo) undertook a nation-wide
      case-control study to clarify the risk factors for hip fractures among Japanese
      in 1994. Cases of hip fracture in people aged 65-89 were selected from 21
      hospitals in seven areas of Japan. Two sex- and age-matched controls were
      selected from the same residential area for each case using resident registration
      lists. During this 1-year survey, 249 cases of hip fractures (43 men and 206
      women) were reported. The following risk factors for hip fractures were
      identified using multivariate analysis: past history of stroke with hemiplegia,
      sleep disturbance, sleeping in a Western-style bed, and drinking more than 3 cups
      of coffee daily.

PMID- 15984420
TI  - Epidemiology of osteoporosis in Japan.

PMID- 15984421
TI  - In vivo characterization of skeletal phenotype of genetically modified mice.
AB  - Genetically modified mouse models provide an important tool for understanding of
      the roles of specific gene in skeletal growth, development, and aging.
      Appropriate study design is essential for characterization of skeletal phenotype
      of these mice. It is important to characterize the bone status of the different
      phases of skeletal development including the early rapid growth, attainment of
      peak bone mass, and age-related bone loss phases. In C57BL/6 strain mice,
      cancellous and cortical bone mass rapidly increases with age before 3 months of
      age, and reaches the peak cancellous bone mass at approximately 6-8 months of
      age, while cortical bone mass continuously increases until 12 months of age.
      Thereafter, age-related decrease in bone mass occurs. According to these
      observations, at least three different age groups need to be evaluated for bone
      status to cover the different phases of the life span: 1-3 months of age for
      rapid growth, 6-9 months for peak bone mass, and >12 months for aged phases.
      Furthermore, bone resorption and formation activities on all bone surfaces
      (periosteal, endocortical, intracortical, and cancellous) need to be evaluated.
      In this article, we briefly summarize our findings in the estrogen receptor-beta
      knockout (BERKO) and the P2X7 receptor (an ATP-gated ion channel) knockout mice.
      In BERKO female mice, bone status at 6, 13, and 21 months of ages was evaluated
      as compared with the wild-type littermate controls. We found that estrogen
      receptor-beta plays an inhibitory role in periosteal bone formation and
      longitudinal and radial growth during the growth period, whereas it plays a role
      in stimulation of bone resorption, bone turnover, and bone loss on cancellous and
      endocortical bone surfaces during the aging process. We also found that ER-beta
      knockout improves the survival rate between 6 and 21 months of age. In P2X7R
      knockout mice, bone status at 2, 5, 9, and 15 months of age was evaluated for
      both sexes as compared with their wild-type littermate controls. We found that
      P2X7R plays a role in stimulating periosteal and cancellous bone formation and
      inhibiting cancellous bone resorption during the growth period.

PMID- 15984422
TI  - Noninvasive monitoring of changes in structural cancellous bone parameters with a
      novel prototype micro-CT.
AB  - Characterization of trabecular bone structures requires necropsy of animals
      followed by a labor-intense histomorphometric or ex vivo micro-CT analysis. We
      tested the novel vivaCT40 from Scanco Medical AG (Bassersdorf, Switzerland),
      which allows monitoring such changes repeatedly in anesthetized rats and mice.
      Postmenopausal osteoporosis: in 8-month-old ovariectomized (OVX) rats, the
      vivaCT40 was capable of picking up the decrease in trabecular bone volume and
      trabecular thinning as well as the decrease in the number of trabecular elements
      as a function of time. The bone anabolic effects of parathyroid hormone [hPTH(1
      34)], which resulted in an increase in trabecular thickness but not their number,
      as well as the bone protective effect of the two antiresorptive agents zoledronic
      acid (ZA) and 17-alpha ethinylestradiol (aEE), were detected correctly with the
      vivaCT40. Adjuvans arthritis: the vivaCT40 allowed measuring trabecular bone loss
      caused by periarticular inflammation in a rat model of adjuvans arthritis and
      demonstrated the bone protective effect of dexamethasone (DM). In addition, it
      was possible to image the subtle erosive lesions in subchondral bone caused by
      the inflammatory processes. Tumor osteolysis: the vivaCT40 allowed monitoring of
      the progressive osteolytic response following the local administration of
      4T1luc2000 tumor cells into the tibia metaphysis of nude mice. The potent
      protective effect of ZA on tumor osteolysis was demonstrated. In summary, the new
      vivaCT40 can monitor the effects of known agents and diseases such as
      osteoporosis, inflammatory arthritis, and tumor invasion on 3-D trabecular
      microarchitecture accurately, repeatedly, reliably, and quickly in anesthetized
      rats and mice. The scanner represents a breakthrough for noninvasive imaging and
      structural measurements in small rodents.

PMID- 15984423
TI  - Mouse models in skeletal physiology and osteoporosis: experiences and data on
      14,839 cases from the Hamburg Mouse Archives.
AB  - Our understanding of the developmental biology of the skeleton, like that of
      virtually every other subject in biology, has been transformed by recent advances
      in human and mouse genetics, but we still know very little, in molecular and
      genetic terms, about skeletal physiology. Thus, among the many questions that are
      largely unexplained are the following: why is osteoporosis mainly a women's
      disease? How is bone mass maintained nearly constant between the end of puberty
      and the arrest of gonadal functions? Molecular genetics has emerged as a powerful
      tool to study previously unexplored aspects of the physiology of the skeleton.
      Among mammals, mice are the most promising animals for this experimental work.
      The input that transgenic animals can offer to our field depends on our means of
      phenotypic characterization of the mouse skeleton. In fact, full appreciation of
      the skeletal characteristics of a given mouse model requires the application of
      standardized protocols for noninvasive imaging, histology, histomorphometry,
      biomechanics, and individually adapted in vitro and in vivo analysis. Over the
      past years we have established a mouse archive that consists of 14,839 cases from
      more than 120 different mouse models that we have phenotypically characterized in
      Hamburg. Today, this is one of the biggest databases on the mouse skeleton. This
      review focuses on one aspect of skeletal physiology, namely skeletal aging, and
      demonstrates that mouse models can be a valuable tool to gain insights in certain
      facets of skeletal physiology that have been unexplored previously.

PMID- 15984424
TI  - Biopolymer-based delivery systems for advanced imaging and skeletal tissue
      specific therapeutics.
AB  - There is considerable advantage in developing tissue-specific delivery systems
      for therapeutic and diagnostic applications. Synthetic water-soluble polymeric
      delivery systems have been developed to allow selective delivery of therapeutic
      and imaging agents to musculoskeletal tissues. For mineralized tissues, bone
      targeting agents such as aspartic acid octapeptide could concentrate the polymer
      conjugates to bone surfaces including resorption sites, which was demonstrated
      with routine bone histomorphometry. For bone-associated soft tissues, other
      targeting approaches based on pathophysiological properties unique to the local
      tissue environment, such as the leaky vasculature in arthritic joints, were
      utilized to achieve the selective deposition of the polymeric delivery systems to
      the desired sites. For this study, magnetic resonance imaging (MRI) was used to
      assess real-time pharmacokinetics and biodistribution of the MRI contrast agent
      conjugated polymer in major organs including skeletal tissues. The MRI data were
      then correlated with other standard imaging methods such as pQCT and DXA as well
      as routine histopathology and skeletal histomorphometry. Clearly, biopolymeric
      delivery systems may be used to improve the pharmacological and pharmacokinetic
      properties of different therapeutic agents for musculoskeletal diseases such as
      osteoporosis and arthritis. In addition, this or related technologies may also be
      useful to improve diagnosis and medical imaging with positron emission
      tomography, gamma scintigraphy, or other technologies.

PMID- 15984425
TI  - Absorptiometric assessment of muscle-bone relationships in humans: reference,
      validation, and application studies.
AB  - This report summarizes some preliminary absorptiometric (DXA, QCT/pQCT) studies
      from our laboratory, supporting the following assumptions. 1. In Homo sapiens at
      all ages, natural proportionality between DXA-assessed bone mineral mass (bone
      mineral content, BMC) and muscle mass (lean mass, LM) of the whole body or limbs
      is specific for ethnicity, gender, and reproductive status, but not for body
      weight, height, or body mass index. 2. This proportionality is sensitive to many
      kinds of endocrine-metabolic perturbations. 3. Percentilized or Z-scored charts
      of the BMC/LM correlations as determined in large samples of healthy individuals
      can provide a diagnostic reference for evaluating proportionality in different
      conditions. 4. Employing exclusively DXA, this methodology can be applied to
      discriminate between "disuse-related" and "metabolic" osteopenias based on the
      finding of normal or low BMC/LM percentiles or Z-scores respectively, with
      important therapeutic and monitoring implications.

PMID- 15984426
TI  - Assessment of bone quality using micro-computed tomography (micro-CT) and
      synchrotron micro-CT.
AB  - The latest micro-computed tomography (micro-CT) can provide ultrahigh-resolution
      images with resolution of less than 10 microm. Geometric three-dimensional (3-D)
      parameters, including the orientation, shape, and connectivity of trabeculae, are
      particularly helpful in understanding complex 3-D structure. Micro-CT is helpful
      for studying bone changes in various pathophysiological states and assessing
      changes in microarchitecture after treatment with antiosteoporotic agents.
      Trabecular microarchitecture is strongly related to bone strength, and 3-D micro
      CT data can be used to assess bone biomechanical properties with the help of
      finite-element analysis. High photon flux from synchrotron X-ray sources reveals
      precise bone surface structure, and the monochromaticity of the beam is suitable
      for performing accurate density measurements. The preliminary results of an in
      vivo study of microarchitecture are also shown. Human vertebral microstructure
      can be revealed using multidetector row CT at a resolution of 200 x 200 x 300
      microm. Analysis using high-resolution CT microstructure was found to be more
      useful in identifying subjects at high risk of fracture than clinical bone
      density measurements using dual X-ray absorptiometry.

PMID- 15984427
TI  - Application of micro-CT assessment of 3-D bone microstructure in preclinical and
      clinical studies.
AB  - As the mechanical competence of trabecular bone is a function of its apparent
      density and 3-D distribution, assessment of 3-D trabecular structural
      characteristics may improve our ability to understand the pathophysiology of
      osteoporosis, to test the efficacy of pharmaceutical intervention, and to
      estimate bone biomechanical properties. We have studied ovariectomy-induced
      osteopenia in rats and its treatment with agents such as estrogen and sodium
      fluoride. We have demonstrated that 3-D micro-computed tomography (microCT) can
      directly quantify mouse trabecular and cortical bone structure with an isotropic
      resolution of 6 microm(3). MicroCT is also useful for studying osteoporosis in
      mice and phenotypes of mice with gene manipulation, such as SHIP-knockout mice,
      which are severely osteoporotic due to increased numbers of hyperresorptive
      osteoclasts, PTHrP heterozygous-null mice, and mice with Zmpste24 deficiency.
      MicroCT can quantify osteogenesis in mouse Ilizarov leg-lengthening procedures,
      osteoconduction in a rat cranial defect model, and structural changes in
      arthritic rabbits, rats, and mice. In clinical studies, we evaluated longitudinal
      changes in the iliac crests. Paired bone biopsies from the same premenopausal and
      postmenopausal women showed the changes in 3-D trabecular structure, such as
      decreased trabecular thickness, shifting of trabecular model from platelike
      structure to rodlike structure, and decreased degree of anisotropy were
      remarkable. Treatment with PTH in postmenopausal women with osteoporosis
      significantly improved trabecular morphology with a shift toward a more platelike
      structure, increased trabecular connectivity density, and increased cortical
      thickness. Paired bone biopsy specimens from the iliac crest in postmenopausal
      women with osteoporosis before and an average of 2 years after beginning of
      estrogen replacement therapy demonstrated that posttreatment biopsies showed a
      significant change in the ratio of plates to rods and statistically insignificant
      changes in other 3-D trabecular parameters. Thus, microCT can characterize 3-D
      structure of various animal models, and the longitudinal changes in 3-D bone
      microarchitectural integrity that deteriorates in the transmenopausal period, is
      preserved with HRT, and is improved with PTH treatment in postmenopausal women.

PMID- 15984428
TI  - [Anatomy and physiology in word and image "cell metabolism"].

PMID- 15984429
TI  - [German drug policy also successful in European comparison].

PMID- 15984430
TI  - [Drug therapy in childhood and adolescence. A challenge between patient
      protection and therapy safety].

PMID- 15984431
TI  - [Manual ventilation in resuscitation of premature and newborn infant in the
      delivery room. II].

PMID- 15984432
TI  - [Preventive vaccination in infancy and preschool age].

PMID- 15984433
TI  - [The responsibilities of nursing care and pediatric nursing are incompletely
      regulated--legal exclusions do not exist].

PMID- 15984434
TI  - [Mobile support team system. An interdisciplinary service model of pediatric and
      adolescent psychiatry at the Heidelberg University Clinic].

PMID- 15984435
TI  - [Patient education responsibility: basic requirements of effective patient
      education].

PMID- 15984436
TI  - [When children die... reflections of a pediatric nurse].

PMID- 15984437
TI  - [Teaching unit "providing space and time--play and activities" this time
      differently].

PMID- 15984438
TI  - [Qualification measure for home nursing care at the Siegen DRK pediatric clinic].

PMID- 15984439
TI  - [The faces of Botox].

PMID- 15984440
TI  - [Botulinum toxin--interventional neuropediatrics in spastic movement disorders in
      childhood].
AB  - Botulinumtoxin A (BTX) is widely used for the treatment of spastic movement
      disorders in childhood. Safety and local efficacy of BTX are well documented by
      the experience of many users and verified by several clinical trials. Indications
      for the use of BTX in children include facilitation of care, better tolerance of
      ortheses as well as the quantitative and qualitative improvement of motor
      abilities. This article differentiates clinical indications for which the use of
      BTX has been proven from those in which effectiveness is only suspected or is yet
      unclear.

PMID- 15984441
TI  - [A trip around the world--the 2002 Better Days Camp].

PMID- 15984442
TI  - [References for therapy of acute diarrhea in infancy--reliable, fast and adapted
      to the child].

PMID- 15984443
TI  - [Information and counseling of family caregivers in "pediatric home nursing"].

PMID- 15984444
TI  - ["Premature delivery and then what?"].

PMID- 15984445
TI  - [Vietnam culture shock. Numerous weeks of participation on a neonatal department
      in Hue, Vietnam].

PMID- 15984446
TI  - [Successful start. Report of experiences by the mother of a premature infant].

PMID- 15984447
TI  - [Anna--"letting her lie there"].

PMID- 15984448
TI  - [Sr. Caroline at work. The day following vacation].

PMID- 15984449
TI  - [Poisonous and less toxic plants. 59].

PMID- 15984450
TI  - [Change of dressings in tube feeding: treatment or basic nursing care?].

PMID- 15984451
TI  - [Art and culture in the hospital for "anyone"].

PMID- 15984452
TI  - [Child kinesics].

PMID- 15984453
TI  - [Interdisciplinary model project neurodermatitis--education for children and
      adolescents].

PMID- 15984454
TI  - [MBA in health management/management & health].

PMID- 15984455
TI  - [Minor morphogenetic errors--minor manifestations of major significance].

PMID- 15984456
TI  - [Indications for sleep laboratory studies in psychiatrically symptomatic children
      and adolescents].
AB  - Many mental and behavioural disorders during childhood and adolescence are
      associated with sleep difficulties. A polysomnography is seldom needed but
      indicated in following cases: In a general view when there is suspected
      obstructive sleep apnea syndrome (OSAS), excessive daytime sleepiness or
      suspected nocturnal seizures. Specific mental disorders with indication of
      polysomnography are: Diagnostic unclear and dangerous parasomnias, emotional
      disorders in case of differing sleep perception, Attention-deficit Hyperactivity
      Disorder (ADHD) and Tourette Syndrome with suspected (additional) OSAS, Restless
      Legs Syndrome (RLS) or Periodic Limb Movement Disorder (PLMD). Further
      indications are -therapy-resistant insomnia and sleep-wake-rhythm-disorders.

PMID- 15984457
TI  - [Sleep disorders in childhood and adolescence].
AB  - Sleep disorders in children are very common and their impact on emotional and
      cognitive functions is considerable. Various pathogenetic factors have to be
      considered, especially a disturbed sleep-wake rhythm but also organic or
      psychiatric causes. Symptoms and pathogenetic factors for sleep disorders in
      children are quite different from adults. In children especially parent-child
      interactional factors and developmental aspects of the sleep architecture have to
      be taken into account what necessitates a different diagnostic approach. This
      article describes systematically typical sleep disorders in children and gives
      practical advices for an anamnestic and diagnostic access to the subject.

PMID- 15984458
TI  - [Why women and men want (no) children].

PMID- 15984459
TI  - ["Lowenherz Pediatric Hospice"--life to the last breath for small patients].

PMID- 15984460
TI  - [Pediatric nurse with heart (defect)].

PMID- 15984461
TI  - [7th Gluckskafer specialty workshop].

PMID- 15984462
TI  - ["Revolutionary" reconsideration of the "Optimal sleeping environment of the
      infant for prevention of sudden infant death" topic].

PMID- 15984463
TI  - [Creativity in the pediatric clinic. About enjoyable creativity at the pediatric
      bedside].

PMID- 15984464
TI  - [Job description of a mentor in the clinic for children and adolescence and
      practical application to nursing routine].

PMID- 15984465
TI  - [Healing concepts in dealing with grief and pain of parents whose child died].

PMID- 15984466
TI  - [Letter concerning the article "Botulinum toxin", KKS 3/03, p. 95].

PMID- 15984467
TI  - [Data protection in the hospital and rights to patient information of health
      insurance].

PMID- 15984468
TI  - [Nursing under scrutiny].

PMID- 15984469
TI  - [How safe is our water"].

PMID- 15984470
TI  - [Proximology or the emergence of a new discipline].

PMID- 15984471
TI  - [Nurse firefighters: who are they?].

PMID- 15984472
TI  - [Nurse firefighters, the passion of engagement. Interview by Helene Delmotte].

PMID- 15984473
TI  - Psychophysical estimates of the number of spectral-reflectance basis functions
      needed to reproduce natural scenes.
AB  - Theoretical analyses of spectral reflectances of natural surfaces suggest that
      their perceived colors can be well reproduced by approximations comprising
      combinations of three or four spectral basis functions. The aim of the present
      work was to assess psychophysically the number of basis functions necessary to
      reproduce entire natural outdoor scenes. Hyperspectral images of 20 such scenes
      were each subjected to a principal component analysis and then reproduced with a
      variable number of basis functions. The quality of the color approximation under
      daylight illumination was quantified theoretically in CIELAB space and
      psychophysically by spatial and temporal two-alternative forced-choice
      measurements in which the original and the approximated images were compared on a
      calibrated color monitor. Although five basis functions produced on average unit
      error in CIELAB space, original images were visually indistinguishable from their
      approximations only if there were at least eight basis functions. The combination
      of the spectral diversity of the natural world and the observed levels of color
      discrimination suggest that estimates of the minimum number of basis functions
      necessary to reproduce natural scenes may need to be revised upward.

PMID- 15984474
TI  - Psychophysical study of the visual sun location in pictures of cloudy and
      twilight skies inspired by Viking navigation.
AB  - In the late 1960s it was hypothesized that Vikings had been able to navigate the
      open seas, even when the sun was occluded by clouds or below the sea horizon, by
      using the angle of polarization of skylight. To detect the direction of skylight
      polarization, they were thought to have made use of birefringent crystals, called
      "sun-stones," and a large part of the scientific community still firmly believe
      that Vikings were capable of polarimetric navigation. However, there are some
      critics who treat the usefulness of skylight polarization for orientation under
      partly cloudy or twilight conditions with extreme skepticism. One of their
      counterarguments has been the assumption that solar positions or solar azimuth
      directions could be estimated quite accurately by the naked eye, even if the sun
      was behind clouds or below the sea horizon. Thus under partly cloudy or twilight
      conditions there might have been no serious need for a polarimetric method to
      determine the position of the sun. The aim of our study was to test
      quantitatively the validity of this qualitative counterargument. In our
      psychophysical laboratory experiments, test subjects were confronted with
      numerous 180 degrees field-of-view color photographs of partly cloudy skies with
      the sun occluded by clouds or of twilight skies with the sun below the horizon.
      The task of the subjects was to guess the position or the azimuth direction of
      the invisible sun with the naked eye. We calculated means and standard deviations
      of the estimated solar positions and azimuth angles to characterize the accuracy
      of the visual sun location. Our data do not support the common belief that the
      invisible sun can be located quite accurately from the celestial brightness
      and/or color patterns under cloudy or twilight conditions. Although our results
      underestimate the accuracy of visual sun location by experienced Viking
      navigators, the mentioned counterargument cannot be taken seriously as a valid
      criticism of the theory of the alleged polarimetric Viking navigation. Our
      results, however, do not bear on the polarimetric theory itself.

PMID- 15984475
TI  - Effect of rotational invariance on the monostatic characteristics of matched
      bodies.
AB  - It is shown analytically and numerically that a matched epsilon = mu reciprocal
      object with rotational symmetry will not produce any backscattering when
      illuminated along the axis of symmetry unless the body is invariant un der a
      rotation by 180 degrees. The purpose of this work is to generalize the monostatic
      theorem of Weston to arbitrary rotational symmetry, thereby providing a basic
      rule for scattering by complex bodies. The theory is illustrated by application
      to a few selected scatterers.

PMID- 15984476
TI  - Mie resonances of dielectric spheres in face-centered cubic photonic crystals.
AB  - With use of plane waves as a basis for the band-structure calculation of a
      periodic assembly of highly refringent microspheres, it can be shown that
      resonance-mode frequencies of isolated dielectric spheres show up in the band
      structures. The strongly localized bands provided by the photonic-crystal
      analysis is compared with exact calculations made in spherical symmetry for an
      isolated microsphere. This comparison sheds some light on the effectiveness of
      the methods based on the description of mode coupling and, in particular, on the
      validity of tight-binding approaches of the description of photonic band
      structures. In addition, examining the effect of modifying the distance
      separating the spheres in the lattice, makes it easy to visualize the overlap
      between the modes of individual spheres. Thus quantitative information is
      provided on the geometry needed to feed energy into low-angular-momentum
      morphology-dependent resonances from a sharp source of the evanescent field and
      on the lifetime of these modes, when the resonances are disturbed by the
      proximity of a dielectric object of similar radius.

PMID- 15984477
TI  - Inelastic scattering on particles with inclusions.
AB  - The investigation of particles with inclusions is of high interest in many parts
      of scientific research. Raman scattering is very good at yielding information on
      the internal composition of the particle. We use a geometrical-optics-based
      technique to determine the angle dependence of the inelastic scattering on
      particles with several spherical inclusions.

PMID- 15984478
TI  - Intermode light diffusion in multimode optical waveguides with rough surfaces.
AB  - A theoretical analysis of incoherent intermode light power diffusion in multimode
      dielectric waveguides with rough (corrugated) surfaces is presented. The
      correlation length a of the surface-profile variations is assumed to be
      sufficiently large (a less less than lambda/2pi) to permit light scattering into
      the outer space only from the modes close to the critical angles of propagation
      and yet sufficiently small (a less less than d, where d is the average width of
      the waveguide) to permit direct interaction between a given mode and a large
      number of neighboring ones. The cases of a one-dimensional (1D) slab waveguide
      and a two-dimensional cylindrical waveguide (optical fiber) are analyzed, and we
      find that in both cases the partial differential equations that govern the
      evolution of the angular light power profile propagating along the waveguide are
      1D and of the diffusion type. However, whereas in the former case the effective
      conductivity coefficient proves to be linearly dependent on the transverse-mode
      wave number, in the latter one the linear dependence is for the effective
      diffusion coefficient. The theoretical predictions are in reasonable agreement
      with experimental results for the intermode power diffusion in multimode (700 x
      700) optical fibers with etched surfaces. The characteristic length of dispersion
      of a narrow angular power profile evaluated from the correlation length and
      standard deviation of heights of the surface profile proved to be in good
      agreement with the experimentally observed changes in the output angular power
      profiles.

PMID- 15984479
TI  - Joint blind restoration and surface recovery in photometric stereo.
AB  - We address the problem of simultaneous estimation of scene structure and
      restoration of images from blurred photometric measurements. In photometric
      stereo, the structure of an object is determined by using a particular
      reflectance model (the image irradiance equation) without considering the
      blurring effect. What we show is that, given arbitrarily blurred observations of
      a static scene captured with a stationary camera under different illuminant
      directions, we still can obtain the structure represented by the surface
      gradients and the albedo and also perform a blind image restoration. The surface
      gradients and the albedo are modeled as separate Markov random fields, and a
      suitable regularization scheme is used to estimate the different fields as well
      as the blur parameter. The results of the experimentations are illustrated with
      real as well as synthetic images.

PMID- 15984480
TI  - Imaging with tilted surfaces: an efficient matrix method for the generalized
      Scheimpflug condition and its application to rotationally symmetric
      triangulation.
AB  - An efficient two-dimensional matrix method is presented that facilitates the
      design of optical systems with tilted surfaces for which the requirement or
      knowledge of the orientation of the image plane is necessary, i.e., for which a
      generalized Scheimpflug condition is needed. In more general terms, the method
      results in imaging properties of second-order expansion, but the method is
      linear. Therefore the complexity of the design process is considerably reduced.
      The strength of the design method is demonstrated in detail for a novel
      application in which a reflective optical system of several surfaces is required
      for rotationally symmetric triangulation.

PMID- 15984481
TI  - Superresolution imaging from limited-aperture optical diffracted field data.
AB  - The use of an optical waveguide to attain a numerical aperture of unity in
      computational coherent optical imaging applications is described. It is shown
      that for the case of a one-dimensional (slitlike) object radiating into an
      optical waveguide consisting of two plane-parallel mirrors the complex field
      amplitude across any cross section of the waveguide contains sufficient
      information to reconstruct the object's transmittance function with a numerical
      aperture of unity. We include the derivation of an inversion algorithm for
      performing the object reconstruction as well as computer simulations of the
      procedure.

PMID- 15984482
TI  - Mach-Zehnder interferometer for piston and tip-tilt sensing in segmented
      telescopes: theory and analytical treatment.
AB  - A study is presented of a Mach-Zehnder interferometer for the measurement of
      phasing errors of the type found in segmented telescopes. We show that with a
      pinhole much larger than the Airy disk and an optical path difference between the
      arms equal to a quarter of the wavelength, the interferometric signal is related
      to the second derivative of the wave front. In this condition the signal is
      produced mostly by the segmentation errors and is marginally sensitive to other
      aberrations including atmospheric turbulence. The signal has distinguishable
      symmetric and antisymmetric properties that are related to segment aberrations.
      We suggest using the antisymmetric component of the signal to retrieve piston,
      tip, and tilt. The symmetric component of the signal serves as an estimate of the
      measurement error. In this way we proceed with a study of the errors associated
      with the misalignment of the interferometer, the segment edge imperfections, and
      the nonaveraged atmospheric perturbations. The entire study is performed on a
      theoretical basis, and numerical simulations are used to cross check the
      analytical results.

PMID- 15984483
TI  - Adaptive finite-element method for diffraction gratings.
AB  - A second-order finite-element adaptive strategy with error control for one
      dimensional grating problems is developed. The unbounded computational domain is
      truncated to a bounded one by a perfectly-matched-layer (PML) technique. The PML
      parameters, such as the thickness of the layer and the medium properties, are
      determined through sharp a posteriori error estimates. The adaptive finite
      element method is expected to increase significantly the accuracy and efficiency
      of the discretization as well as reduce the computation cost. Numerical
      experiments are included to illustrate the competitiveness of the proposed
      adaptive method.

PMID- 15984484
TI  - Effective grating theory for resonance domain surface-relief diffraction
      gratings.
AB  - An effective grating model, which generalizes effective-medium theory to the case
      of resonance domain surface-relief gratings, is presented. In addition to the
      zero order, it takes into account the first diffraction order, which obeys the
      Bragg condition. Modeling the surface-relief grating as an effective grating with
      two diffraction orders provides closed-form analytical relationships between
      efficiency and grating parameters. The aspect ratio, the grating period, and the
      required incidence angle that would lead to high diffraction efficiencies are
      predicted for TE and TM polarization and verified by rigorous numerical
      calculations.

PMID- 15984485
TI  - Light scattering from a birefringent cylinder, spider silk, slimmer than the
      wavelength approaches dipole radiation.
AB  - Using a plane-polarized laser of wavelength lambda = 543.5 or 441.6 nm and spider
      silk, we investigated the diffraction of a transparent cylinder of diameter D
      approximately lambda - lambda/5 at normal incidence. The measured pattern
      corresponded well to the one calculated by a rigorous solution of the theory for
      the problem. The birefringent index and D of the sample could be determined
      simultaneously. The experimental data of the scattering cross section for D <
      lambda/4 suggested that the data approached dipole radiation.

PMID- 15984486
TI  - Task-based optimization and performance assessment in optical coherence imaging.
AB  - Optimization of an optical coherence imaging (OCI) system on the basis of task
      performance is a challenging undertaking. We present a mathematical framework
      based on task performance that uses statistical decision theory for the
      optimization and assessment of such a system. Specifically, we apply the
      framework to a relatively simple OCI system combined with a specimen model for a
      detection task and a resolution task. We consider three theoretical Gaussian
      sources of coherence lengths of 2, 20, and 40 microm. For each of these coherence
      lengths we establish a benchmark performance that specifies the smallest change
      in index of refraction that can be detected by the system. We also quantify the
      dependence of the resolution performance on the specimen model being imaged.

PMID- 15984487
TI  - Coherence theory of electromagnetic wave propagation through stratified N-layer
      media.
AB  - The theory of second-order coherence in connection with wave propagation through
      a stratified N-layer (SNL) medium is developed. Especially, the influence of the
      SNL medium on the propagation of the coherence generated by a given state of
      coherence at the entrance plane of the medium is considered. The generalization
      of the van Cittert-Zernike theorem is obtained, and the propagation of the second
      order coherence from a quasi-homogeneous surface distribution or a rough surface
      is calculated. Furthermore, the influence of SNL media on the coherence
      properties of a pulse is calculated.

PMID- 15984488
TI  - Determination of refractive indices of porcine skin tissues and intralipid at
      eight wavelengths between 325 and 1557 nm.
AB  - We constructed an automated reflectometry system for accurate measurement of
      coherent reflectance curves of turbid samples and analyzed the presence of
      coherent and diffuse reflection near the specular reflection angle. An existing
      method has been validated to determine the complex refractive indices of turbid
      samples on the basis of nonlinear regression of the coherent reflectance curves
      by Fresnel's equations. The complex refractive indices of fresh porcine skin
      epidermis and dermis tissues and Intralipid solutions were determined at eight
      wavelengths: 325, 442, 532, 633, 850, 1064, 1310, and 1557 nm.

PMID- 15984489
TI  - Spectral density matrix description of polarization mode dispersion.
AB  - We introduce a power spectral density matrix formalism that incorporates both the
      pulse shape and the field polarization and can therefore easily describe averages
      over random fluctuations of the local birefringence vector. We demonstrate that
      quantities such as the differential time delay, power diffusion, and decoherence
      effects can be obtained directly from the equations of motion for the power
      density matrix. This approach can be applied to pulses with arbitrary frequency
      dependent polarization and intensity distributions and in particular makes
      possible the minimization of the eye-opening penalty through the proper choice of
      the initial pulse profile.

PMID- 15984490
TI  - Modal analysis of M-type-dielectric-profile optical fibers in the weakly guiding
      approximation.
AB  - We study the applicability of the weakly guiding approximation (WGA) to the modal
      analysis of an M-type optical fiber in which a ring-shaped core lies between two
      uniform cladding layers. Besides being dependent on the refractive indices, the
      accuracy of the approximation is shown to be substantially affected by the
      transverse dimensions of the core. The accuracy is characterized by calculating
      an overlap integral between the exact and WGA-approximated modal fields. Fibers
      that have an inner cladding similar to the outer cladding, or similar to vacuum,
      are considered in detail. The feasibility of the WGA in determining the fiber
      parameters for single-mode guidance is also discussed.

PMID- 15984491
TI  - Robust phase demodulation of interferograms with open or closed fringes.
AB  - We present two robust algorithms for fringe pattern analysis with partial-field
      and closed fringes. The algorithm for partial-field fringe patterns is presented
      as a refinement method for precomputed coarse phases. Such an algorithm consists
      of the minimization of a regularized cost function that incorporates an outlier
      rejection strategy, which causes the algorithm to become robust. On the basis of
      the phase refinement method, we propose a propagative scheme for phase retrieval
      from closed-fringe interferograms. The algorithm performance is demonstrated by
      demodulating closed-fringe interferograms with complex spatial distribution of
      stationary points and gradients in the illumination components.

PMID- 15984492
TI  - Iterative focus detection in hologram tomography.
AB  - Hologram tomography is a two-step method for three-dimensional topometry of
      extended objects. The first step consists of the hologram recording with a single
      laser pulse of 35 ns duration and storage in a photosensitive material. In the
      second step the hologram is optically reconstructed and digitized, which leads to
      a set of two-dimensional projections at different axial positions. A maximization
      of a focus measure has to be performed to extract the surface position out of the
      projections. Unlike with well-established methods, where the comparison of
      sharpness values is done parallel to the optical axis, we propose an iterative
      solution to perform the maximization along the direction of image formation,
      which is evaluated for each surface point individually. This leads to a better
      reproducibility of the surface in the off-axis regions.

PMID- 15984493
TI  - Principal formulas of integrated photoelasticity in terms of characteristic
      parameters.
AB  - Recent advances in integrated photoelasticity have opened the possibility of
      determining tomographically arbitrary three-dimensional stress fields. Since
      photoelastic tomography is based on experimental measurement of the
      characteristic parameters, the dependence of these parameters on the stress
      distribution on a light ray is considered in detail. The possibility of
      determining certain integrals of the stress components is analyzed, and the
      linear approximation of integrated photoelasticity has been rigorously treated.

PMID- 15984494
TI  - Irreducible representations of finite groups in the T-matrix formulation of the
      electromagnetic scattering problem.
AB  - For particles with discrete geometrical symmetries, a group-theoretical method is
      presented for transforming the matrix quantities in the T-matrix description of
      the electromagnetic scattering problem from the reducible basis of vector
      spherical wave functions into a new basis in which all matrix quantities become
      block diagonal. The notorious ill-conditioning problems in the inversion of the Q
      matrix are thus considerably alleviated, and the matrix inversion becomes
      numerically more expedient. The method can be applied to any point group. For the
      specific example of the D6h group, it is demonstrated that computations in the
      new basis are faster by a factor of 3.6 as compared with computations that use
      the reducible basis. Most importantly, the method is capable of extending the
      range of size parameters for which convergent results can be obtained by 50%.

PMID- 15984495
TI  - Local spectrum analysis of field propagation in an anisotropic medium. Part I.
      Time-harmonic fields.
AB  - The phase-space beam summation is a general analytical framework for local
      analysis and modeling of radiation from extended source distributions. In this
      formulation, the field is expressed as a superposition of beam propagators that
      emanate from all points in the source domain and in all directions. In this Part
      I of a two-part investigation, the theory is extended to include propagation in
      anisotropic medium characterized by a generic wave-number profile for time
      harmonic fields; in a companion paper [J. Opt. Soc. Am. A 22, 1208 (2005)], the
      theory is extended to time-dependent fields. The propagation characteristics of
      the beam propagators in a homogeneous anisotropic medium are considered. With use
      of Gaussian windows for the local processing of either ordinary or extraordinary
      electromagnetic field distributions, the field is represented by a phase-space
      spectral distribution in which the propagating elements are Gaussian beams that
      are formulated by using Gaussian plane-wave spectral distributions over the
      extended source plane. By applying saddle-point asymptotics, we extract the
      Gaussian beam phenomenology in the anisotropic environment. The resulting field
      is parameterized in terms of the spatial evolution of the beam curvature, beam
      width, etc., which are mapped to local geometrical properties of the generic wave
      number profile. The general results are applied to the special case of uniaxial
      crystal, and it is found that the asymptotics for the Gaussian beam propagators,
      as well as the physical phenomenology attached, perform remarkably well.

PMID- 15984496
TI  - Local spectrum analysis of field propagation in an anisotropic medium. Part II.
      Time-dependent fields.
AB  - In Part I of this two-part investigation [J. Opt. Soc. Am. A 22, 1200 (2005)], we
      presented a theory for phase-space propagation of time-harmonic electromagnetic
      fields in an anisotropic medium characterized by a generic wave-number profile.
      In this Part II, these investigations are extended to transient fields, setting a
      general analytical framework for local analysis and modeling of radiation from
      time-dependent extended-source distributions. In this formulation the field is
      expressed as a superposition of pulsed-beam propagators that emanate from all
      space-time points in the source domain and in all directions. Using time
      dependent quadratic-Lorentzian windows, we represent the field by a phase-space
      spectral distribution in which the propagating elements are pulsed beams, which
      are formulated by a transient plane-wave spectrum over the extended-source plane.
      By applying saddle-point asymptotics, we extract the beam phenomenology in the
      anisotropic environment resulting from short-pulsed processing. Finally, the
      general results are applied to the special case of uniaxial crystal and compared
      with a reference solution.

PMID- 15984497
TI  - Comment on "Scheimpflug and high-resolution magnetic resonance imaging of the
      anterior segment: a comparative study".
AB  - In a recent paper, Koretz et al. [J. Opt. Soc. Am. A 21, 346 (2004)] conclude
      that the results of the "corrected Scheimpflug technique" to obtain the shape of
      the human lens differ significantly from their magnetic resonance imaging (MRI)
      data. We demonstrate that the conclusions are based on incorrect statistical
      methods. A straightforward statistical comparison shows that there is no
      significant difference between the corrected Scheimpflug results and the MRI
      data.

PMID- 15984498
TI  - Choice and palliative care: what do we mean?

PMID- 15984499
TI  - Transitions in the lives of patients with End Stage Renal Disease: a cause of
      suffering and an opportunity for healing.
AB  - The treatment of End Stage Renal Disease (ESRD) successfully prolongs the
      survival of patients with kidney disease but requires that ESRD patients cope
      with frequent deleterious changes in their health and life situation, and
      shortened survival. Although the nephrology team is well-equipped to deal with
      the medical and technical aspects of care, it is less well-equipped to help
      patients with the impact of the difficult human transitions that come with
      dialysis and transplant treatment. Times of great challenge can also be
      opportunities for personal growth and healing but this often requires outside
      support. We need to develop new resources specifically aimed at helping ESRD
      patients complete important life transitions and more research on the frequency
      and impact of these events.

PMID- 15984500
TI  - Identifying palliative care patients with symptoms of depression: an algorithm.
AB  - INTRODUCTION: Even though depression has serious and wide-ranging effects on
      outcomes in palliative care, errors in the identification of depressed patients
      are common. OBJECTIVES: To examine the clinical validity of widely publicised one
      and two-question screening tools for depression in two palliative care settings.
      Also, to examine the construct validity and acceptability of a new empirically
      derived algorithm. METHOD: Participants were Australian palliative care patients
      in an inpatient hospice (n=22) or the community (n=69). Patients completed an
      unstructured interview about their feelings, questions relevant to three
      reference standards, two screening questions for depression and questions about
      the acceptability of the screening questions. RESULTS: The clinical validity of
      the one- and two-question screening tools did not generalise across the two care
      settings. In contrast, the algorithm met stringent criteria for clinical validity
      for two reference standards in both settings. The algorithm also selectively
      identified patients whose unstructured interviews referred to themes consistent
      with depression. The algorithm includes potentially sensitive questions about
      anhedonia and depressed affect. However, almost all patients and staff reported
      that asking such questions soon after referral was acceptable. CONCLUSIONS: A
      four-question algorithm designed to identify patients who warrant follow-up for
      depression showed clinical validity, generalizability and construct validity, and
      the content was acceptable to patients and clinicians.

PMID- 15984501
TI  - Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a
      systematic review.
AB  - BACKGROUND: Brain metastases are the most common intracranial tumour in adults,
      estimated to occur in up to 40% of patients with cancer. Despite being used in
      clinical practice for 50 years, the effectiveness of whole brain radiotherapy for
      the treatment of brain metastases remains uncertain. OBJECTIVES: To assess the
      effectiveness of whole brain radiotherapy (WBRT) on survival and quality of life.
      To identify whether patient performance status, number of brain metastases,
      extent of extracranial disease and primary site of cancer are important effect
      modifiers. DESIGN: Systematic literature review. METHODS: Electronic searches of
      four databases, augmented by hand searches of the most frequently encountered
      journal and assessment of the reference lists of consensus statements and all
      retrieved papers. Included papers underwent structured data extraction,
      assessment and qualitative synthesis. RESULTS: Thirty-two primary studies were
      included, with a range of study designs, methodological quality, pre-treatment
      variables, interventions and outcome measures. From the limited evidence
      available, survival appeared to increase when patients were selected by
      performance status (survival increasing from approximately three to seven months
      in high performance status groups, as defined by Karnofsky performance status or
      Recursive Partitioning Analysis classification). The evidence suggests no
      survival benefit when patients with poor performance status were treated with
      whole brain radiotherapy. No studies undertook direct measurement of patients'
      quality of life. Surrogate measures of patients' quality of life, such as
      improvement in neurological function or improvement/maintenance of KPS > or =70,
      produced response rates ranging from 7 to 90%. CONCLUSION: The heterogeneity of
      study designs, quality and outcomes necessitates caution in interpreting the
      review findings. WBRT appears to be of benefit in higher performance status
      patients but not in low performance status patients. This suggests a basis for
      current practice, however further robust trial evidence is required.

PMID- 15984502
TI  - Lymphoedema: estimating the size of the problem.
AB  - Lymphoedema is a problem frequently encountered by professionals working in
      palliative care. This article reviews the evidence on the magnitude of the
      problem of lymphoedema in the general population and provides evidence on
      specific high risk groups within it. Prevalence is a good indicator of the burden
      of disease for chronic problems such as lymphoedema, as it indicates the numbers
      of patients who require care. Incidence is indicative of changes in the causes of
      lymphoedema and the success of any prevention programmes. Both are important
      means of assessing the current level of need and the potential for the changing
      needs in managing this condition. Problems exist in all studies in relation to
      precise definitions of lymphoedema, inconsistent measures to assess differential
      diagnosis and poorly defined populations. While there is some evidence of high
      rates in relation to breast cancer therapy, the total burden of lymphoedema in
      the general population is largely unknown.

PMID- 15984503
TI  - Should we screen hospice inpatients for orthostatic hypotension?
AB  - Orthostatic hypotension (OH) is defined as a reduction in systolic blood pressure
      of at least 20 mm Hg or a reduction in diastolic blood pressure of at least 10 mm
      Hg within three minutes of standing, with a reported prevalence of 40% in the
      hospice setting. Dizziness, falls and fractures have been attributed to OH and
      some cases of symptomatic OH might be reversible. This study explored the case
      for screening hospice inpatients for OH. Fifty-nine patients were screened up to
      five times and, whilst the detection rate was 27%, in no case was it
      reproducible. There was no statistical association between orthostatic symptoms
      and the detection of OH, and no patients benefited from the screening process. On
      closer examination of the literature, the current definition of OH might benefit
      from revision, sphygmomanometry is an unsatisfactory screening method and there
      is currently no case for screening hospice inpatients for OH.

PMID- 15984504
TI  - Why are bereaved family members dissatisfied with specialised inpatient
      palliative care service? A nationwide qualitative study.
AB  - BACKGROUND: In order to improve the quality of palliative care, we can learn from
      bereaved families who were dissatisfied with the care they received. The primary
      aim of this study was to explore why bereaved families were dissatisfied with
      specialized inpatient palliative care. METHODS: This qualitative study formed
      part of a nationwide questionnaire survey administered to 1225 bereaved family
      members of cancer patients who died in certified palliative care units in Japan.
      The participants were 22 consecutive family members who reported a greater need
      for improvement in care. Data were analysed by the content analysis. RESULTS: The
      reasons that the bereaved families listed are classified into 27 categories and
      seven themes: (1) lack of perceived support for maintaining hope; (2) lack of
      perceived respect of individuality, especially in attitudes toward death; (3)
      perceived poor quality of care, especially psychological care, not being treated
      with dignity and inadequate explanation from physicians; (4) inadequate staffing
      and equipment, especially physician availability; (5) unavailability of timely
      administration; (6) lack of accurate information about palliative care units; and
      (7) family's practical and economic burden. CONCLUSIONS: This study identified
      the multiple sources of dissatisfaction with specialized inpatient palliative
      care for bereaved families. These findings could be useful in developing a more
      desirable system of specialised inpatient palliative care.

PMID- 15984505
TI  - Supportive care in the cancer setting: rhetoric or reality?
AB  - BACKGROUND: Since 1995, UK cancer policy has been directed at organizational
      changes to secure improvements in treatment outcomes and quality of supportive
      care for cancer patients. The substantial increase in hospital-based specialist
      cancer nurses (SCNs) during this time suggests they have a major role to play in
      the delivery of supportive care. AIM: To explore how SCNs implemented their role
      in the context of organizational change and newly-formed multidisciplinary teams.
      METHODS: Twenty-nine SCNs participated in observation and/or interviews,
      resulting in 135 hours of observation and in-depth semi-structured interviews
      with 17 SCNs. Data were collected and analysed using a grounded theory approach.
      RESULTS: The prominence of the treatment agenda--the process of investigating,
      diagnosing and treating cancer--presented the biggest challenge to the delivery
      of supportive care. The treatment agenda influenced how support was offered,
      determined professional boundaries and relegated support to a subordinate
      position in patient care. CONCLUSIONS: Access to supportive care is a central
      tenet of current cancer policy and crucial to the philosophy of patient-centred
      care. While SCNs are essential to the delivery of supportive care, this study
      highlights the challenges they encounter in organizations which prioritise
      treatment and improvements to treatment outcomes.

PMID- 15984506
TI  - The last days of life of nursing home patients with and without dementia assessed
      with the palliative care outcome scale.
AB  - The aim of this study was to assess the Palliative care Outcome Scale (POS) for
      terminally ill nursing home (NH) patients in the Netherlands. METHODS: A
      prospective observational study of patients with a life-expectancy of six weeks
      or less in 16 Dutch NHs. NH staff rated the patient characteristics and measured
      palliative care with the POS, including items on physical, psychosocial,
      informational, spiritual and practical aspects. RESULTS: POS nonscores (not
      applicable; unknown) were mainly found in the psychosocial and spiritual domains,
      particularly in patients with dementia. Mean scores for non-demented patients and
      patients with dementia were favourable for the majority of the POS items.
      CONCLUSION: According to the NH staff, fairly good quality care was provided, but
      the psychosocial and spiritual aspects of care need to be addressed more in the
      last days of the dying NH patient's life. The results indicate that the POS is an
      appropriate instrument to assess not only cancer patients, but also non-cancer
      and (moderately) severely demented patients.

PMID- 15984507
TI  - Voices of the terminally ill: uncovering the meaning of desire for euthanasia.
AB  - This study aimed to better understand the meaning of desire for euthanasia. An
      hermeneutic approach was undertaken using a purposively selected sample of
      advanced cancer patients who desired euthanasia while receiving palliative care.
      Unstructured interviews were conducted with six participants, which were
      audiotaped, transcribed and analysed. This approach allowed in-depth exploration
      and interpretation of the patients' lived experience. The findings illustrated a
      timeline from previous wellness to approaching death with five major themes: (1)
      reality, (2) perception, (3) anticipation, (4) desire and (5) holding
      environment. The desire for euthanasia is not confined to physical or
      psychosocial concerns relating to advanced cancer, but incorporates hidden
      existential yearnings for connectedness, care and respect, understood within the
      context of the patients' lived experience. Euthanasia requests cannot be taken at
      face value but require in-depth exploration of their covert meaning, in order to
      ensure that the patients' needs are being addressed adequately.

PMID- 15984508
TI  - Integrated care pathway for the last days of life.

PMID- 15984509
TI  - Tendon rupture as a complication of corticosteroid therapy.

PMID- 15984510
TI  - [Recent development in research and management of cancer anorexia-cachexia
      syndrome].
AB  - Cachexia is among the most debilitating and life-threatening aspects of cancer,
      and is more common in children and elderly patients. Associated with anorexia,
      fat and muscle tissue wasting, psychological distress, and a lower quality of
      life, cachexia arises from a complex interaction between the cancer and the host.
      This process results from a failure of the adaptive feeding response seen in
      simple starvation and includes cytokine production, release of lipid-mobilizing
      and proteolysis-inducing factors, and alterations in intermediary metabolism.
      Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the
      hypothalamic effect of excessive negative feedback signaling from leptin, a
      hormone secreted by adipose tissue, which is an integral component of the
      homeostatic loop of body weight regulation. This could be done by persistent
      inhibition of feeding-stimulatory circuitry including neuropeptide Y. Cachexia
      should be suspected in patients with cancer if an involuntary weight loss of
      greater than five percent of premorbid weight occurs within a 3-6-month period.
      The two major options for pharmacological therapy have been either progestational
      agents or corticosteroids. However, knowledge of the mechanisms of cancer
      anorexia-cachexia syndrome has led to, and continues to lead to, effective
      therapeutic interventions for several aspects of the syndrome. These include
      antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids,
      eicosapentanoic acid, cannabinoids, melatonin, and thalidomide-all of which act
      on the feeding-regulatory circuitry to increase appetite and inhibit tumor
      derived catabolic factors to antagonize tissue wasting and/or host cytokine
      release. The outcomes of drug studies in cancer cachexia should focus on the
      symptomatic and quality-of-life advantages rather than simply on nutritional end
      points, since the survival of cachexia cancer patients may be limited to weeks or
      months due to the incurable nature of the underlying malignancy. Communication
      among physicians and other health care professionals provides the patient with a
      multidisciplinary approach to care. The patient record will be an excellent
      resource to document a plan of care and patient responses to treatment.
      Psychological distress and psychiatric disorders are common among cancer
      patients. These problems are also as common among the family members of people
      with cancer. The use of psychological and behavioral interventions in cancer is
      increasing, and recent studies have suggested that some of these techniques may
      affect quality of life and, perhaps, survival rates. Evaluations of relaxation,
      hypnosis, and short-term group psychotherapy have suggested some benefit with
      regard to anorexia and fatigue, although the population most likely to benefit
      from these interventions has not yet been determined. Because weight loss
      shortens the survival time of cancer patients and decreases performance status,
      effective therapy would extend patient survival and improve quality of life.

PMID- 15984511
TI  - [Translational research on lung cancer--EGFR gene mutation].
AB  - Recent reports that activating mutations of the EGFR have a significant
      association with the response to gefitinib drew much attention. Mutations are
      more frequently observed in Oriental patients, females, non-smokers and
      adenocarcinoma patients, which correspond to patient profiles predictive of a
      good clinical response with gefitinib. In vitro experiments also revealed EGFR
      mutant cell lines are highly sensitive to gefitinib. It seems that development of
      tailor-made therapy of lung cancer would be possible by the test for EGFR gene
      mutations. Furthermore, EGFR mutations are the first molecular change known to
      specifically occur in lung cancer, preferentially in never smokers, especially in
      adenocarcinoma that is increasing in incidence. It is ultimately necessary to
      identify non-tobacco-related carcinogens that cause EGFR mutations for effective
      prevention of lung cancer.

PMID- 15984512
TI  - [Diagnostic imaging of lung cancer on multislice CT (MDCT)].
AB  - Helical CT, and the newest technological development, multislice CT
      (multidetector CT: MDCT), have revolutionized the diagnostic approach to diseases
      of the chest including lung cancer. There are several factors that contribute to
      the important role of multislice CT scanning of the chest: (1) data acquisition
      is so rapid that the scanning of the entire lung can be performed during a single
      breath-hold period; (2) continuous acquisition of thin slices allows the
      improvement of the image quality of multiplanar reconstruction of thoracic
      abnormalities; (3) MDCT may help reduce the radiation dose, so that, compared to
      conventional or single-slice helical CT, the radiation dose is lowered with
      comparable image quality. The advantages of MDCT include both improved nodule
      detection and nodule characterization on lung cancer screening programs, because
      the entire lung can be scanned with thin slice in a single breath-hold without an
      intersection gap. In the evaluation of lung cancer, MDCT will allow improved
      detection of pleural dissemination and hilar lymph node adenopathy because of the
      continuous and narrow scan collimation.

PMID- 15984513
TI  - [Postoperative adjuvant chemotherapy for non-small cell lung cancer].
AB  - Patients with completely resected non-small-cell lung cancer (NSCLC) are subjects
      for postoperative adjuvant treatment. Recently, several randomized trials with a
      large number of enrolled patients have shown that platinum-based chemotherapy has
      potential for improving survival among patients with completely resected NSCLC in
      Western countries. In Japan, uracil-tegafur was also shown to improve survival
      among patients with completely resected stage I adenocarcinoma. This review
      evaluated the role of adjuvant chemotherapy, based on the results of randomized
      trials and meta-analyses.

PMID- 15984514
TI  - [Chemotherapy for advanced non-small cell lung cancer].
AB  - It is well-known that cisplatin-based chemotherapy can prolong the survival of
      patients with advanced non-small cell lung cancer (NSCLC). This report reviews
      the recently published clinical trials of chemotherapy for advanced NSCLC. New
      agents developed in the 1990s such as paclitaxel, docetaxel, gemcitabine,
      vinorelbine and irinotecan prolonged the survival of patients with advanced NSCLC
      by single-agent chemotherapy, and combinations of platinum and one of the new
      agents were superior to existing platinum-based combinations. Accordingly, the
      current standard chemotherapy for previously untreated patients with advanced
      NSCLC is considered to be a two-drug combination consisting of cisplatin and one
      of the new agents. For elderly patients, single-agent chemotherapy using
      vinorelbine or gemcitabine is recommended. However, the usefulness of platinum
      containing chemotherapy for elderly patients has not yet been throughly
      evaluated. As salvage chemotherapy for patients previously treated with
      chemotherapy, the effectiveness of docetaxel is confirmed by two randomized
      trials. However, since many promising agents including pemetrexed and molecular
      targeting agents such as gefitinib, erlotinib and bevacizumab have been currently
      developed, we have to evaluate the usefulness of these agents by well-designed
      clinical trials.

PMID- 15984515
TI  - [Treatment of small cell lung cancer].
AB  - The treatment of choice for limited small-cell lung cancer (SCLC) is platinum
      based chemotherapy combined with early, concurrent thoracic radiotherapy with a
      hyperfractionated regimen. The standard chemotherapy for extensive SCLC in Japan
      is the combination of irinotecan and cisplatin. There are expectations for new
      and effective molecular-target-based drugs for SCLC.

PMID- 15984516
TI  - [New anti-cancer agents--from cytotoxic systemic chemotherapy to target-based
      agents].
AB  - Lung cancer is the leading cause of cancer-related death throughout the world
      including Japan. During the 1990s, new cytotoxic agents such as irinotecan,
      paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive
      single-agent activity in patients with lung cancer. To date, clinical research
      has defined the current standard chemotherapy for advanced non-small cell lung
      cancer (NSCLC) as modern platinum-based doublets considered more efficacious than
      any single regimen and with no added benefit to triplet therapies. However, we
      have reached an efficacy plateau with these agents. Rearrangement of the drug
      combination or change of the drug doses and schedules will not result in
      significant further progress. New, less toxic agents that improve survival and
      quality of life are clearly needed. In the last three decades, we have gained a
      growing understanding of the molecular biologic changes and the complex series of
      cellular signals that allow cancer cells to manifest behavior. This provides an
      opportunity to develop novel therapies aimed at inhibiting some of these changes
      and signals. Targeted agents, primarily the epidermal growth factor receptor
      inhibitors, have led to a new era in the treatment of NSCLC. This paper will
      review the current status of cytotoxic agents and molecular targeted therapy in
      lung cancer potential useful in the treatment of the patients.

PMID- 15984517
TI  - [Problems of case accumulation in a clinical trial of hepatic arterial infusion
      after resection of hepatic metastases: A summary of the study design and
      questionnaire survey of the participating centers in study no. 29-0003 of the
      Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC)].
AB  - A randomized controlled trial of intermittent hepatic arterial infusion of weekly
      high-dose 5-FU (WHF) after resection of hepatic metastases from colorectal cancer
      was conducted to study the survival benefit of two regimens. Patients were
      randomly assigned to receive one of two arms after resection of hepatic
      metastases: the WHF arm (study group), 1000 mg/m2 of 5-FU administered over the
      course of 5 hr once a week by hepatic arterial infusion; or the CVI arm (control
      group), 300 mg/m2 of 5-FU administered as a continuous intravenous infusion daily
      for 5 days followed 2 days' rest. This study is the first randomized trial of
      hepatic arterial infusion chemotherapy with percutaneous hepatic catheter
      placement and assessment of liver drug distribution by CT angiography after
      resection of hepatic metastases from colorectal cancer in the world. Fifty-two
      centers participated, and 91 patients were enrolled. Although the target number
      of patients was not enrolled, problems of this study and future prospects for
      trials of hepatic arterial infusion after resection of hepatic metastases were
      assessed by questionnaire surveys of the participating centers.

PMID- 15984518
TI  - [Changes in tumor marker levels as a predictor of gemcitabine effect on patients
      with unresectable or recurrent pancreatic cancer].
AB  - We studied on possible association between the tumor marker (CEA, CA 19-9, and
      SPan-1) change and the clinical outcome after treatment with gemcitabine (GEM) in
      23 patients with unresectable or recurrent pancreatic cancer. GEM was
      administered intravenously at a standard dose of 1000 mg/m2 weekly. One course
      consisted of weekly administration for 3 weeks followed by 1 week's rest. When
      the adverse effect did not allow the weekly administration, GEM was given bi
      weekly without dose modification. Objective responses were evaluated by computed
      tomography and tumor marker change. Two or more courses were given for only 6
      (26.1%) patients. The number of patients, administered GEM 6 or more times
      including by the weekly and bi-weekly method, was 12 (52.2%). Antitumor effects
      were evaluable in 16 patients. The clinical efficacies were 1 partial response
      (PR), 6 stable disease (SD), and 9 progressive disease (PD). Decreases in tumor
      marker levels were recognized in 9 of the 16 patients. The median survival time
      (MST) of the PR+NC group was significantly longer than that of the PD group (9 vs
      3.5 months; p=0.0151). MST of those in the decreasing tumor marker group was
      significantly longer than the group with no decreases in the tumor markers (7.0
      vs 5.5 months; p = 0.0478). The adverse effects at grade 3 or more were 4 (17.3%)
      leukopenia, 2 (8.7%) thrombocytopenia, and 1 (4.3%) skin toxicity. In conclusion,
      the tumor marker change after GEM treatment may be a predictor of preferable
      prognosis in patients with pancreatic cancer.

PMID- 15984519
TI  - [Pharmacokinetic modulating chemotherapy highly effective for colorectal
      carcinoma metastases to multiple organs].
AB  - AIMS: Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high
      serum 5-fluorouracil (5-FU) concentrations through modulation by uracil. The
      therapeutic efficacy of PMC and the sensitivity of metastatic lesions to 5-FU
      were evaluated in advanced colorectal cancer patients. METHODOLOGY: Thirteen
      patients with colorectal carcinoma metastases to multiple organs were enrolled.
      PMC was initiated with a combination of 400 mg of uracil-tegafur daily and 24
      hour continuous intravenous infusion of 600 mg/m2 of 5-FU once weekly. The 5-FU
      dose was escalated when the disease progressed. When PR was achieved, serum 5-FU
      concentrations were monitored in order to evaluate the chemosensitivity of each
      metastatic lesion to 5-FU. RESULTS: PR in the target lesion was observed in 7 of
      11, 6 of 10, 2 of 2, and 2 of 4 patients with metastatic lesions to the liver,
      lungs, peritoneum and lymph nodes, respectively. The area under the concentration
      time curve (AUC ng x hr/ml) of the 5-FU sufficient to induce PR in pulmonary
      lesions, 3528 to 9684, was significantly higher than for hepatic lesions, 2413 to
      6323 (p = 0.028). The median survival was 13 months. CONCLUSIONS: PMC, having a
      chronomodulating nature, is highly effective in treating colorectal carcinoma
      metastases with a superior safety profile. Pulmonary metastases are more
      resistant to 5-FU than hepatic metastases, as they require a higher 5-FU AUC to
      respond.

PMID- 15984520
TI  - [Phase I study of concurrent radiotherapy with TS-1 and vitamin A (TAR Therapy)
      for head and neck cancer].
AB  - The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR
      therapy) has been effectively used to treat head and neck cancer. The biological
      anti-tumor effect of 5-FU depends on the activity of its metabolizing enzyme,
      dihydropyrimidine dehydrogenase (DPD). TS-1 is a novel oral DPD inhibitory
      fluoropyrimidine (DIF). To improve the anti-tumor effect of FAR therapy, we have
      applied TS-1 in place of 5-FU injection in the combination of Vitamin A and
      radiation (TAR therapy). In this study, we have examined the appropriate duration
      of TS-1 medication and the clinical efficacy and safety of TAR therapy. TS-1 was
      administered orally at a dose of 65 mg/m2 twice a day. Vitamin A (Retinol
      Palmitate: 50,000 U/day) was administered intra-musculary on each day of
      radiation. Radiation was given (1.5-2 Gy/day: 5 days/week) for 30-40 Gy. The
      levels were divided according to the length of TS-1 application as follows: level
      1, 2 weeks; level 2, 3 weeks; level 4, 4 weeks. Grade 4 toxicity of anorexia was
      observed in one case of level 3. We decided that level 2 (3 weeks of TS-1
      administration) was the appropriate length of TS-1 application. TAR therapy is a
      useful concurrent chemo-radiotherapy which might improve the response rate and
      QOL of patients with HNSCC.

PMID- 15984521
TI  - [Toxicity of doxorubicin and cyclophosphamide (60 mg/600 mg/m2) in adjuvant
      chemotherapy for breast cancer].
AB  - We evaluated the toxicity of 4 cycles of doxorubicin (60 mg/m2) and
      cyclophosphamide (600 mg/m2) every 3 weeks (AC 60/600) in adjuvant chemotherapy
      for breast cancer. Between 1994 and 2003, 62 patients received 6 cycles of
      doxorubicin (40 mg/m2) and cyclophosphamide (500 mg/m2) every 3 weeks (AC
      40/500), and 106 patients received AC 60/600 as adjuvant chemotherapy for breast
      cancer. The performance status of all patients was 0 or 1. Toxicity was
      determined using the National Cancer Institute Common Toxicity Criteria (NCI-CTC)
      ver. 2. Grade 3/4 neutropenia was frequent in AC 60/600 (6.5% vs 24.3%, p <
      0.001). However, febrile neutropenia was not significant in either group (1.6% vs
      3.8%, p = 0.39). There was also no statistical difference in the toxicity greater
      than grade 3 of anemia, nausea, vomiting, fatigue, diarrhea and cardiotoxicity.
      There was no treatment-related death in both groups. The number of patients who
      completed chemotherapy was higher in those receiving AC 60/600 than in those
      receiving AC 40/500 (91.9% vs 99.1%, p = 0.026). AC 60/600 is tolerated and
      feasible in adjuvant chemotherapy of breast cancer in Japanese patients from the
      viewpoint of toxicities.

PMID- 15984522
TI  - [Neoadjuvant chemotherapy with intra-arterial infusion in the treatment of
      advanced cervical cancer].
AB  - Neoadjuvant chemotherapy (NAC) with intra-arterial infusion was performed in the
      treatment for 53 patients with advanced cervical squamous cell carcinoma. After
      NAC with intra-arterial infusion of the anticancer agents including cisplatin via
      internal iliac artery or uterine artery, 42 patients received radical
      hysterectomy. The response to therapy was observed in 45 of all patients (84.9%)
      clinically, and 36 of 42 patients (85.7%) pathologically. Cancer cells
      disappeared in 11.9% of patients with cervical invasion, 69.2% with vaginal wall
      invasion and 39.4% with parametrium invasion after NAG. Five-year survival rates
      were 100% in stage I, 71.5% in stage II, 52.2% in stage II and 0% in stage IV.
      The group of patients without cancer in the parametrium after NAC showed a
      significantly better 5-year survival rate than the group with residual cancer in
      the parametrium. According to the results, the elimination of cancer invasion to
      the parametrium by NAC is thought to be important for improvement of the
      prognosis in advanced cervical cancer.

PMID- 15984523
TI  - [A case of head and neck squamous cell carcinoma suffering from acute renal
      failure after methotrexate administrator].
AB  - A 56-year-old man was hospitalized for evaluation of left neck tumor. The biopsy
      of neck lymph node showed a squamous cell carcinoma. Since no primary lesion was
      detected, the diagnosis was primary unknown neck lymph node metastasis. The first
      course of our chemotherapeutic regimen consisted of CDDP, 5-FU, MTX and LV. After
      MTX infusion, the level of serum creatinine increased. Based on laboratory data,
      we diagnosed acute renal failure caused by MTX and added the infusion of Ringer
      and LV. The serum creatinine level decreased to the level before chemotherapy. In
      the second course, chemotherapy with only CDDP and 5-FU was administered, and the
      level of serum creatinine did not increase. In the present case, suitable
      intravenous drip infusion of Ringer's injection prevented irreversible renal
      dysfunction. Since the laboratory data did not show dysfunction of uriniferous
      tubule and renal glomerulus, we considered allergic nephritis as a possibility.

PMID- 15984524
TI  - [A case regarded as an occult breast cancer treated without mastectomy].
AB  - A 51-year-old woman was admitted to our hospital with a chief complaint of left
      axillary tumors. No such tumors were detected in bilateral breasts by ultrasonic
      tomography, mammography, computed tomography, and magnetic resonance imaging. The
      core needle biopsy from the left axillary lymph node was examined, and the
      specimen revealed an occult breast cancer, because the microscopic findings
      resembled the breast cancer organization and immunochemistry revealed positivity
      of the estrogen receptor. The radical left axillary dissection was operated.
      Tamoxifen and FEC 100 6 cycles were selected as adjuvant treatment. At one year
      after operation, she has no recurrence. Carcinoma cells had portedly been
      recognized in the mammary gland with 82.7% of the cases who had undergone
      mastectomy for occult breast cancer. However, in many cases, the patient's
      consent for mastectomy was not obtained like as in this case, and the choice of
      treatment is often difficult. We considered that the case's accumulation was
      necessary to verify the possibility of the mastectomy omission to an occult
      breast cancer, presented the case report.

PMID- 15984525
TI  - [A case of recurrent esophageal cancer successfully treated with weekly
      paclitaxel in combination with radiotherapy].
AB  - A 48-year-old man underwent subtotal esophagectomy for pStage III (pT 3 pN 3)
      thoracic esophageal carcinoma on June 20, 2002, in combination with chemotherapy
      (5-FU 500 mg/day day 1-14, CDDP 10 mg/day day 1-14, VDS 3 mg on days 1 and 8)
      before and after the operation. Recurrence was seen 7 months after the operation
      in right pleura and lower mediastinum. Chemo (same regimen)-radiotherapy (50 Gy)
      was then performed but without effect. Thereafter, lung and upper mediastinal
      metastases were found, and weekly administration of paclitaxel (70 mg/m2, day 1,
      8, 15, q 4w) was initiated in combination with radiotherapy (40 Gy). Two cycles
      of treatment resulted in PR, and CR was achieved after the 8th cycle was
      completed. Although treatment was terminated after the 12 th cycle due to
      development of peripheral neuropathy (grade 2), CR was still maintained 8 months
      after the completion of treatment. These results suggested the effectiveness of
      the treatment in cases that show resistance to conventional 5-FU-based
      chemotherapy.

PMID- 15984526
TI  - [A case of advanced gastric cancer effectively treated by TS-1 for 4 years].
AB  - The patient was a 66-year-old man who had advanced gastric cancer with metastasis
      to liver and lymph nodes. He received daily oral administration of 100 mg of TS-1
      for 28 days followed by 14 days rest as one treatment course. After 2 coures,
      regression of the primary lesion and reduction in size of the liver and lymph
      metastases were observed.

PMID- 15984527
TI  - [Successfully resected advanced gastric carcinoma after combined chemotherapy of
      TS-1 plus CDDP--a case report].
AB  - A 66-year-old man complained of epigastralgia and a close examination was done. A
      type 3 gastric carcinoma was found. The tumor invading the pancreas and swelling
      lymphnodes around the stomach were confirmed according to abdominal CT. We
      considered it difficult to resect the tumor completely, and so we used combined
      chemotherapy of TS-1 plus CDDP. TS-1 was taken at 120 mg/day for 28 days followed
      by 14 days rest. CDDP was injected at 140 mg on day 8. Because the tumor in the
      stomach changed to scar and swelling lymphnodes diminished after two courses of
      therapy, total gastrectomy was done. After operation, combined chemotherapy of LV
      and 5-FU resulted in no recurrence to date. Although combined chemotherapy of TS
      1 plus CDDP is effective for advanced gastric carcinoma, the number of days TS-1
      is taken and the duration of the preoperative chemotherapy must be investigated
      in forthcoming study.

PMID- 15984528
TI  - [TS-1 treatment for progressive gastric cancer in a patient on chronic dialysis-
      assessment of dosage regimen by monitoring blood concentrations of therapeutic
      drugs (TDM)].
AB  - The optimum dose of TS-1 for the treatment of peritoneally disseminated gastric
      cancer in a patient with chronic renal failure undergoing chronic dialysis was
      estimated by monitoring the blood concentrations of 5-FU and gimeracil (CDHP)
      [therapeutic drug monitoring (TDM)] during administration of TS-1. Immediately
      after dialysis, 50 mg or 40 mg of TS-1, corresponding to 50% and 40% of the
      standard dose (100mg for this patient), respectively, was administered orally
      once a day every other day, and TDM was conducted. Compared with the
      pharmacokinetic parameters of 5-FU at the time of the initial administration of
      50 mg or 40 mg of TS-1 and that of cancer patients with normal renal function,
      the AUC shown in the administration of 40 mg was equivalent to that observed with
      a single safe dose of 100 mg in patients with normal renal function. Based on
      this observation, the daily TS-1 dose was set at 40 mg in this patient, and TS-1
      treatment was started after confirming the absence of the accumulation of 5-FU or
      CDHP during repeated administrations. In this treatment protocol, TS-1 was
      administered 11 times at a daily dose of 40 mg every other day immediately after
      dialysis, followed by a rest. This .administration schedule was defined as one
      course. Under these conditions, the patient was treated on an outpatient basis,
      and the treatment could be safely continued without the development of any severe
      adverse events, such as myelosuppression.

PMID- 15984529
TI  - [Complete response of recurrent gastric cancer to chemotherapy with TS-1 and CPT
      11--a case report].
AB  - A 58-year-old man with gastric cancer who had undergone distal gastrectomy on
      February 8, 2001 was revealed to have anorexia, and was diagnosed with a local
      recurrence in anastomosis by upper GI examination in August 2003. In September
      2003, he was given combination chemotherapy with TS-1 50 mg/m2 (days 1-14) and
      CPT-11 80 mg/m2 (days 1, 8) every 3 weeks. A complete response (CR) was confirmed
      by endoscopy in December 2003. At present, he has been receiving chemotherapy
      with only TS-1 50 mg/m2 as a maintenance therapy and continuing CR. However, a
      trial of combination therapy with TS-1 plus CPT-11 is ongoing, and this
      combination chemotherapy may well achieve a high response rate. Because the
      adverse events of this chemotherapy have been mild and tolerable in some of our
      cases, this regimen is considered very useful.

PMID- 15984530
TI  - [A case of peritoneal dissemination of gastric cancer successfully treated by
      irinotecan combined with cisplatin].
AB  - We report a case of a 59-year-old man with advanced gastric cancer. Distal
      gastrectomy with lymph node dissection (D1) was performed. Pathological staging
      was IV (T3N1CY1), and the operation resulted in curability C. The serum CA19-9
      level before the operation was 201 U/ml, and it did not normalize 3 months after
      the operation. Postoperative chemotherapy (TS-1, 100 mg/day) was performed.
      Because the tumor markers such as CEA and CA19-9 level elevated 5 months after
      the operation, triweekly docetaxel therapy and TS-1 administration (days 1-14)
      were performed. We disbontinued this therapy after 2 courses due to adverse
      reactions, such as leukopenia (grade 4) and liver dysfunction (grade 2).
      Peritoneal dissemination was diagnosed by the appearance of ascites and thickness
      of the peritoneum 11 months after the operation. So the patient was treated with
      a biweekly combination chemotherapy of irinotecan (CPT-11 60 mg/m2) and cisplatin
      (CDDP 30 mg/m2). Eight courses of this therapy induced partial remission and
      normalization of the serum CEA level. No major adverse reaction to this therapy
      was observed. The partial remission and good patient's QOL were achieved during
      follow-up 7 months after the administration of CPT-11 plus CDDP. This case
      suggests that patients with recurrent peritoneal dissemination of gastric cancer
      could benefit from CPT-11 with CDDP combination therapy as a second-line or third
      line treatment.

PMID- 15984531
TI  - [A case of curatively resected AFP producing gastric cancer that responded
      remarkably to 1 course of TS-1 and showed complete loss of multiple liver
      metastatic tumors].
AB  - A 73-year-old woman was admitted to our hospital for evaluation of
      hypochondralgia, and a thorough examination revealed an AFP producing gastric
      cancer with multiple liver metastases. One course of TS-1 100 mg/day for 4 weeks
      and discontinuation for 2 weeks was started from February, 2003. After 3 months,
      the level of AFP reduced remarkably from 53,700 ng/ml to the normal limit. The
      metastatic tumors in the liver showed regression, and after 14 months, CT
      scanning showed that the tumors had disappeared. Since the size of the original
      tumor showed no change, distal gastrectomy was performed, and curability A was
      achieved. We consider this rare case has significant value in terms of treatment
      of AFP producing gastric cancer with multiple liver metastases. We think the
      combination of surgery and chemotherapy such as TS-1 will lead to a better
      prognosis in such cases.

PMID- 15984532
TI  - [Pharmacokinetics and adverse event of TS-1 administered through gastrostomy].
AB  - We administered TS-1 to a patient with advanced oropharyngeal carcinoma who
      underwent a gastrostomy because of swallowing difficulties. TS-1 was dissolved in
      50 degrees C water and administered through a gastrostogavage tube. The
      pharmacokinetics of TS-1 were then investigated. The plasma 5-FU level was
      measured, and adverse events appearing after administration were monitored. The
      highest plasma 5-FU concentration on day 1 was 138.7 ng/ml; this level was
      obtained in a sample drawn 2 hours after the administration of TS-1. The highest
      plasma 5-FU concentration of TS-1 on day 8 (159.8 ng/ml) was also drawn 2 hours
      after the administration of TS-1. No major adverse events were observed in the
      patient. In particular, no toxic effects on the digestive systems were observed.
      Furthermore, the administration of TS-1 through a gastrostomy was safe. Such a
      procedure could also be used in patients with naso-gastric feeding tubes. We
      conclude that the administration of TS-1 through either a gastrostomy or a naso
      gastric feeding tube may be a new administration method that can improve the
      quality of life (QOL) of patients with advanced and/or recurrent head and neck
      carcinoma.

PMID- 15984533
TI  - [A case of metastatic submandibular lymphnode treated successfully with
      palliative oral (5-FU + PSK) chemotherapy in the elderly].
AB  - The patient was a 87-year-old woman diagnosed as type 2 advanced colon cancer in
      the ascending colon. The patient underwent right hemicolectomy. The pathological
      diagnosis showed poorly-differentiated adenocarcinoma, si, ly2, v1, n0 (0/41) and
      Stage IIIa. The postoperative course was uneventful, and she was discharged on
      POD 23. But a left submandibular lymph node enlarged rapidly within two months
      after the operation. Aspiration cytology of the lymph node indicated poorly
      differentiated adenocarcinoma, and she was diagnosed as recurrent colon cancer.
      Combined chemotherapy of 5-FU (200 mg/day/po) and PSK (3.0 g/day/po) was started
      as palliative chemotherapy. The metastatic lymph nodes were reduced in size
      within two months after the treatment. Oral administration of 5-FU+PSK succeeded
      without serious adverse effects or worsening of quality of life. Ten months
      later, no recurrence was detected on physical examination or computed tomography.
      We conclude that palliative oral (5-FU+PSK) chemotherapy is useful for recurrent
      colon cancer in the elderly because of its excellent safety and effectiveness.

PMID- 15984534
TI  - [Graft-versus-ATLL effect induced by abrupt discontinuation of immunosuppression
      following allogeneic bone marrow transplantation].
AB  - A 46-year-old man was admitted to our hospital with swelling of a neck lymph node
      in June, 2002, and was diagnosed with adult T-cell leukemia/lymphoma (ATLL). As
      ATLL cells were detected in the peripheral blood after two courses of multi-agent
      chemotherapy (LSG 15), the treatment was changed to biweekly CHOP therapy. After
      two courses, hematological remission was achieved. Allogeneic bone marrow
      transplant (allo-BMT) from HTLV- negative and HLA-matched sibling donor was
      performed (conditioned with cyclophosphamide 60 mg/kg x 2 and total body
      irradiation 12 Gy). Cyclosporine A (CsA) and short-term methotrexate (MTX) were
      used for graft-versus-host disease prevention. Though the HTLV- provirus DNA
      (Southern blot) disappeared, HTLV-I provirus DNA (real-time PCR) T-cell receptor
      ygammachain gene rearrangement DNA (Southern blot) were detected in bone marrow
      after allo-BMT. MRD disappeared after the withdrawal of CsA. After the allo-BMT
      transplant, a graft-versus-ATLL (GVATLL) effect may be induced by abrupt
      discontinuation of immunosuppression.

PMID- 15984535
TI  - [Case reports of use of TS-1 for second/third-line chemotherapy for advanced
      colorectal carcinoma].
AB  - The usefulness of TS-1 as second/third-line therapy was evaluated in 7 patients
      with stage IIIb/IV colorectal cancer in whom the response to prior 5-FU/l-LV+CPT
      11 therapy administered at our hospital had been rated as progressive disease
      (PD). The initial dose level of TS-1 was set at 80 mg/m2. The median follow-up
      period was 8 months. The response rate to TS-1 therapy was 14.3% (1/7). Four
      cases (57.1%) were rated as showing partial response (PR) or no change (NC). The
      median time to treatment failure (TTF) was 117 days. Thus, relatively
      satisfactory tumor dormancy was achieved in IFL-resistant cases. All adverse
      reactions observed were grade 2 or less severe. These results suggest that TS-1
      used as the second/third-line therapy will contribute to improving the prognosis
      of patients with advanced or recurrent colorectal cancer.

PMID- 15984536
TI  - [Sentinel lymph node concept in patients with esophageal cancer].
AB  - It is not uncommon that first lymph node involvement appears at a distant lymph
      node not at a nearest node from the primary lesion in patients with esophageal
      cancer. Identification of the sentinel node, which permits the detection of the
      first draining node from a primary lesion, is expected to individualize the
      treatment of esophageal cancer. From our study in 23 patients with esophageal
      cancer using Tc-99 m tin colloids, the sentinel node concept seemed to be
      applicable to patients with esophageal cancer (-pT2). However, injection
      techniques and intraoperative probe searching for hot nodes are more difficult
      and uncertain in esophageal cancer compared to superficial cancers such as breast
      cancer and malignant melanoma. Further studies are necessary to reliably apply
      the sentinel node biopsy technique to patients with esophageal cancer.

PMID- 15984537
TI  - [Tumor markers in malignant lymphoma].
AB  - For malignant lymphoma, there is no highly sensitive or specific tumor marker for
      diagnosis. However, some tumor markers such as cell surface marker or karyotypic
      analysis are useful for diagnosis combined with other clinical and pathological
      information. International Prognostic Index (IPI), Follicular Lymphoma
      International Prognostic Index (FLIPI), and International Prognostic Score (IPS)
      are useful to predict prognosis, and utilized to decide therapeutic strategy of
      aggressive non-Hodgkin's lymphoma (NHL), follicular lymphoma and Hodgkin's
      lymphoma, respectively. Non-specific biological markers such as soluble
      interleukin-2 receptor (sIL-2 R) are utilized to evaluate therapeutic effect. In
      this paper, we describe about the significance of these tumor markers in
      malignant lymphoma.

PMID- 15984538
TI  - Business models for biomaterials in regenerative medicine.
AB  - The emergence of new therapeutic methods and technologies, including those
      associated with regenerative medicine, has required new thinking about
      regulation, reimbursement and business models. Some of the issues that
      particularly relate to the materials used in these technologies are discussed in
      this article.

PMID- 15984539
TI  - New trends in biological evaluation of medical devices.
AB  - More extensive material characterisation and increased determination of
      toxicological risks are now required when evaluating new medical devices. The new
      requirements together with other changes in the ISO 10993 series described here
      suggest how companies can adjust their approach.

PMID- 15984540
TI  - Essential considerations when designing a filter device.

PMID- 15984541
TI  - Technology development for medical implants.
AB  - Work on new technologies for biomaterials and an implantable power source for
      implants is described here. Common requirements have been identified to start the
      development of technological solutions that can be applied to a range of
      products.

PMID- 15984542
TI  - Being sucessfully disruptive.
AB  - Small companies can more easily create "disruptive" innovation than large
      companies. This article discusses why and how they can introduce some basic
      processes to make sure they do not become victims of their own success.

PMID- 15984543
TI  - US importer and distributor requirements.
AB  - A medical device manufacturer who exports products to the United States (US) may
      risk success in this activity by not being aware of US importer and distributor
      requirements. This article discusses the requirements and actions that nonUS
      manufacturers should take to ensure these requirements are met.

PMID- 15984544
TI  - Human tissue scaffolds: measured progress ensures a safe future.
AB  - Measurement scientists are helping the tissue-engineering community develop
      robust manufacturing routes and a regulatory framework for tissue scaffolds.
      Activities are described that are underway to make tissue engineered products a
      commercial reality.

PMID- 15984545
TI  - Innovation and the medical devices Farady partnership.
AB  - Demand for development of new generation medical devices has led many governments
      to support medical-sector research. In the United Kingdom, the Medical Devices
      Faraday Partnership was created to establish a collaborative network that would
      enhance the transfer of good ideas into new products and processes. The services
      it offers medical device manufacturers are outlined here.

PMID- 15984547
TI  - Laser marking and medical devices.

PMID- 15984546
TI  - Routes to the future German health economy.
AB  - A fundamental reorganisation of the health-care system to introduce a market
      orientation, more transparency and patient autonomy is proposed as the way to
      deliver the required high-quality care of the future.

PMID- 15984548
TI  - Best practice for electromagnetic compatibility.

PMID- 15984549
TI  - The tiny RNA world.

PMID- 15984550
TI  - Toward a remembrance of things past: deciphering Alzheimer disease.

PMID- 15984551
TI  - Autophagy in development, tumor suppression, and innate immunity.

PMID- 15984552
TI  - Breeding molecules to spy on cells.

PMID- 15984553
TI  - Lymphocyte tolerance: central is central.

PMID- 15984554
TI  - Some thoughts on the tree of life.

PMID- 15984555
TI  - Hierarchy of events regulating neural crest induction.

PMID- 15984556
TI  - Getting a SureStart in life.

PMID- 15984557
TI  - SRE: a programme to support community nurses.

PMID- 15984558
TI  - Gender politics and families.

PMID- 15984559
TI  - A concept analysis of partnership with clients.
AB  - The aim of this first paper of two about partnership working with clients is to
      define and clarify partnership as it is practised within health visiting, by
      identifying the central notions of partnership working in practice. The aim of
      the second paper will be to describe an evaluation of a training course in
      partnership working for health visitors. Partnership is a word in common usage
      within the health professions but its meaning is ill-defined. A literature search
      was undertaken to identify ways in which previous authors have used the concept
      within nursing, counselling and health visiting. Rodgers' approach to concept
      analysis was undertaken to seek clarity for the concept. This revealed the ways
      in which various authors have used the word, an analysis of its defining
      attributes, surrogate terms, antecedents, consequences and a concluding
      definition. The results showed that partnership with clients in health visiting
      can be defined as a respectful, negotiated way of working together that enables
      choice, participation and equity, within an honest, trusting relationship that is
      based in empathy, support and reciprocity. It is best established within a model
      of health visiting that recognises partnership as a central tenet. It requires a
      high level of interpersonal qualities and communication skills in staff who are,
      themselves, supported through a system of clinical supervision that operates
      within the same partnership framework.

PMID- 15984561
TI  - Army dependents: childhood illness and health provision.
AB  - This small qualitative study explored attitudes of a group of Army wives to
      childhood illness and their expectations of health provision. The author's
      practice serves a population mainly comprising of Army dependents where GP
      attendance rates are double the national average. Two focus groups were organised
      using health visitor groups attached to the practice. Transcripts were examined
      to produce a framework for semi-structured interviews with nine mothers, who were
      selected by purposive sampling. Mothers were asked about symptoms, coping, social
      problems, decisions to take action, health provision and support. Data were
      analysed and sorted, using the principles of grounded theory, into four main
      themes: attitude to child's illness, coping, Army culture and accessibility to
      health services. Many Army wives appear to suffer from high levels of stress. It
      seemed that the coping ability of the mother was affected by the constant
      turbulence and isolation of Army life. While mothers displayed a knowledge of
      common illnesses, they had fears of the unknown and of life threatening
      illnesses. They sometimes managed childhood illness at home owing to lack of
      transport. The author concluded that some Army wives suffer from stress and lack
      confidence in their mothering skills when their children are ill, which may be
      due, in part, to the constant cycle of postings and isolation from family and
      services. They need easily accessible health facilities and information regarding
      these services. Communication should be encouraged between civilian services and
      the Army. It appears that Army dependents require more support from their GP
      practice than the average civilian family, offering opportunity for nurses and
      health visitors to provide alternative and proactive services.

PMID- 15984562
TI  - Breastfeeding: benefits and implications. Part two.
AB  - Recent guidelines from the Department of Health recommend exclusive breastfeeding
      for the first six months (26 weeks) of an infant's life with the late
      introduction of solids being cited as protective against the development of
      asthma, eczema and atopy. However, it has been suggested that national and
      international recommendations for the age of introducing solid foods (weaning)
      are founded on insufficient evidence. In part two of her update, June Thompson
      looks at the conflicting literature regarding whether exclusive breastfeeding for
      six months conveys significant benefits for babies and if current recommendations
      that a delayed introduction of solids is protective against the development of
      asthma and allergy are supported by the evidence.

PMID- 15984560
TI  - Women's experiences of managing mastitis.
AB  - The first paper in this series (last month), discussed study methodology and the
      measurement of the incidence of mastitis, which was shown to peak at four and 12
      weeks. It concluded that the reporting pattern by women experiencing mastitis
      affects the measurement of reported incidence. This paper presents the
      qualitative data generated through interviews with 56 women. It analyses their
      theories of causation that may account for the two peaks in incidence. Factors
      most likely to contribute to the risk of developing mastitis were identified by
      women as incorrect positioning and incomplete emptying. Expressing by hand or
      pump, and hurried or infrequent feeding patterns, were also thought to be
      practices associated with mastitis. They considered that these practices were
      associated with social pressures such as the care of older children. The study
      concluded that respondents' theories about causation illustrate the interactive
      nature of anatomical, physiological, pathological and social risk factors. The
      two peaks in incidence occur at times when the intensity of this interaction
      increases. Existing research findings support these theories and present
      opportunities to change and develop professional practice.

PMID- 15984564
TI  - Metal accumulation and apoptosis in the alimentary canal of Lumbricus terrestris
      as a metal biomarker.
AB  - The chloragogenous tissue and the intestinal epithelium of adult earthworms,
      Lumbricus terrestris, sampled from sites with and without volcanic activity in
      the Azores were submitted to hematoxylin/eosin staining, autometallography and
      TUNEL-test in order to quantify the radial thickness of both tissues, their
      relative abundance of metals and apoptosis levels. Metals were visualized,
      through light microscopy, as black silver deposits (BSD) mostly in the
      chloragogenous tissue. The lowest radial thickness values of both tissues were
      found in the active volcanic sites, as well as the highest BSD and apoptosis
      levels. The BSD extent in the chloragogenous tissue, semi-quantified by
      stereology, exhibited a positive correlation with the apoptosis levels and a
      negative one with the radial thickness of both tissues. Thus, the variation of
      the radial thickness of both tissues, but especially of the chloragogenous
      tissue, which could reflect different cellular turnover rates caused by exposure
      to metals, is suggested as a biomarker of effect for metal exposure in
      terrestrial worms inhabiting volcanic environments.

PMID- 15984565
TI  - Exposure to high fluoride concentration in drinking water will affect
      spermatogenesis and steroidogenesis in male albino rats.
AB  - Sodium fluoride (NaF) administered orally to adult male rats at a dose level of
      4.5 ppm and 9.0 ppm for 75 days caused significant decrease in the body weight,
      brain index and testicular index. A significant decrease in sperm count, sperm
      motility, sperm viability and sperm function (HOS positive) with increased sperm
      abnormalities was also observed in NaF-exposed male rats. The activity levels of
      testicular steroidogenic marker enzymes 3beta-hydroxysteroid dehydrogenase (3beta
      HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were significantly
      decreased in NaF-treated rats indicating decreased steroidogenesis and in turn
      spermatogenesis in rats exposed to NaF.

PMID- 15984566
TI  - Alterations in the lipid content of pituitary gland and serum prolactin and
      growth hormone in cadmium treated rats.
AB  - The present study was undertaken to assess whether chronic exposition to cadmium
      (Cd, 0.133 mM per liter for 2 months) through drinking water may affect the lipid
      contents in the pituitary anterior lobe (PAL) of adult male Wistar rats. As
      compared to metal non-exposed controls, PALs exposed to cadmium showed an
      increase in total phospholipid contents, which was associated to an increase of
      the incorporation of [1-14C]-methyl choline into phosphatidylcholine and of [U
      14C]-glucose into total phospholipids. The incorporation of [1-14C]-methyl
      choline into sphingomyelin was not changed. Incorporation of [1-14C]-acetate into
      total fatty acids also increased but incorporation of [1-14C]-acetate into
      cholesterol did not change. The activity of phospholipase D decreased both in
      PALs from Cd exposed rats and in PAL dispersed cells treated with Cd in the
      culture medium from Cd non-exposed rats. In PALS from Cd exposed rats, a decrease
      of serum prolactin and growth hormone concentrations was determined. The results
      shown that cadmium modifies the lipid contents of pituitary gland and directly or
      indirectly the levels of prolactin and growth hormone in serum.

PMID- 15984567
TI  - Signal role for activation of caspase-3-like protease and burst of superoxide
      anions during Ce4+-induced apoptosis of cultured Taxus cuspidata cells.
AB  - The signal events of 1 mM Ce4+ (Ce(NH4)2(NO3)6)-induced apoptosis of cultured
      Taxus cuspidata cells were investigated. The percentage of apoptotic cells
      increased from 0.82% to 51.32% within 6 days. Caspase-3-like protease activity
      became notable during the second day of Ce4+-treatment, and the maximum activity
      was 5-fold higher than that of control cells at the fourth day. When the
      experiment system was pretreated with acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD
      CHO) at 100 microM, caspase-3-like activity resulted in distinct inhibition by
      70% and 77.3% after 3 and 4 days of induction. Furthermore, 100 microM Ac-DEVD
      CHO partially reduced the apoptotic cells by 58.6% and 60.8% at day 4 and 5
      respectively. Ce4+ induced superoxide anions (O2*-) transient burst, and the
      first peak appeared at around 3.7-4 h, the second appeared at about 7 h. Both O2*
      burst and cell apoptosis were effectively suppressed by application of diphenyl
      iodonium (NADPH oxidase inhibitor). Inhibition of O2*- production attenuated
      caspase-3-like activation by 49% and 53.6% during day 3 and 4 respectively. In
      addition, a total of 15 protein spots changed in response to caspase-3-like
      protease activation were identified by two-dimensional gel electrophoresis. These
      results suggest that Ce4+ of 1 mM induces apoptosis in suspension cultures of T.
      cuspidata through O2*- burst as well as caspase-3-like protease activation. The
      burst of O2*- exerts its activity as an upstream of caspase-3-like activation.
      Our results also implicate that other signal pathways independent of an O2*-
      burst possibly participate in mediating caspase-3-like protease activation.

PMID- 15984568
TI  - Metals content in placentas from moderate cigarette consumers: correlation with
      newborn birth weight.
AB  - Cigarette consumption during pregnancy produces deleterious effects in both,
      mother and fetus, some of them due to the presence of toxic elements in cigarette
      smoke, such as cadmium. Placenta constitutes a dual-purpose specimen for
      evaluating the pollutant burden exerted on the mother as well as on the fetus.
      The main objective of this study was to establish a correlation between placental
      concentration and distribution of some metal elements and birth weight of
      neonates delivered by mothers, who were either moderate smokers or nonsmokers.
      Forty nonsmoking and moderate smoking pregnant women paired per age, parity,
      weight, height and body mass index were selected. Smoking was assessed by self
      reported cigarette consumption during pregnancy and urine cotinine concentration
      before delivery. Placental metal concentrations were evaluated by atomic
      absorption spectrometry (copper and cadmium) and neutron activation analysis
      (zinc and iron). Newborns from smokers had lower birth weights compared to
      infants from nonsmokers. Birth weights were correlated with placental cadmium
      concentrations in both, smokers and nonsmokers. Placental zinc and cadmium of
      smokers were mainly located at the maternal side and their levels were higher
      than those found in nonsmoker's placentas. In addition, all metal
      nutrient/pollutant ratios were decreased in the smoker group. In this first study
      performed in our region, we found that moderate smoking mothers deliver neonates
      with decreased birth weight and highly correlated to placental cadmium
      concentration. Decreased metal nutrient/pollutant ratios, a condition here found
      in smokers, may indicate a placental dysfunction, contributing to impair birth
      weight.

PMID- 15984569
TI  - Effects of increased cellular zinc levels on gene and protein expression in HT-29
      cells.
AB  - High cellular zinc concentrations lead to impairments in ATP synthesis and cell
      cycle control particularly in neurons and epithelial cells. The molecular basis
      for these dysfunctions is still not fully elucidated. Here we analyzed the
      effects of a high zinc exposure (10 ppm) on gene and protein expression in the
      human epithelial cell line HT-29. Of the 1176 genes analyzed with cDNA arrays,
      nine differentially expressed genes were identified. Proteome analysis based on
      1310 detected proteins identified 11 molecular targets. Most of the identified
      genes/proteins have not been linked to cellular zinc status before (e.g. PEC-60,
      R-ras3). More than half of the targets participate in ATP production or stress
      response. Therefore, it appears that higher zinc concentrations mediate their
      effects mainly via impairments in cellular energy metabolism and stress response.

PMID- 15984570
TI  - Kinetics of the early subcellular distribution of cadmium in rat hepatocytes.
AB  - The kinetics of the early subcellular distribution of cadmium (Cd) was
      characterized in primary cultures of rat hepatocytes exposed to 10, 50 and 100
      microM Cd in a serum-free WME medium for 10, 30 or 60 min. Our results
      demonstrate a time- and concentration-dependent increase in Cd content with the
      highest metal concentration measured in the cytosol, whereas the lowest was
      observed in the mitochondria. With the exception of early localization in the
      plasma membrane, Cd concentrations in fractions were characterized by the
      following decreasing order of magnitude: cytosol > low density molecules
      approximately nuclei > lysosomes approximately mitochondria. We also found
      evidence for: (i) a two-step process for Cd distribution in the nuclei and
      mitochondria; and (ii) a time-dependent 'slow' process of transfer from the
      plasma membrane to the cytosol. Saturation in Cd uptake was observed at 50 microM
      in most cell fractions at 10 and 30 min, except for the plasma membrane. The lack
      of apparent saturation for Cd accumulation at 60 min was not related to an
      increase in metallothionein synthesis. Altogether, our data provide insights into
      the dynamics of transfer between intracellular compartments, and allow a better
      identification of the organelles that are the most subjected to Cd toxicity for
      early exposure conditions.

PMID- 15984571
TI  - Fungal degradation of calcium-, lead- and silicon-bearing minerals.
AB  - The aim of this study was to examine nutritional influence on the ability of
      selected filamentous fungi to mediate biogenic weathering of the minerals,
      apatite, galena and obsidian in order to provide further understanding of the
      roles of fungi as biogeochemical agents, particularly in relation to the cycling
      of metals and associated elements found in minerals. The impact of three organic
      acid producing fungi (Aspergillus niger, Serpula himantioides and Trametes
      versicolor) on apatite, galena and obsidian was examined in the absence and
      presence of a carbon and energy source (glucose). Manifestation of fungal
      weathering included corrosion of mineral surfaces, modification of the mineral
      substrate through transformation into secondary minerals (i.e. crystal formation)
      and hyphal penetration of the mineral substrate. Physicochemical interactions of
      fungal metabolites, e.g. H+ and organic acids, with the minerals are thought to
      be the primary driving forces responsible. All experimental fungi were capable of
      mineral surface colonization in the absence and presence of glucose but corrosion
      of the mineral surface and secondary mineral formation were affected by glucose
      availability. Only S. himantioides and T. versicolor were able to corrode apatite
      in the absence of glucose but none of the fungi were capable of doing so with the
      other minerals. In addition, crystal formation with galena was entirely dependent
      on the availability of glucose. Penetration of the mineral substrates by fungal
      hyphae occurred but this did not follow any particular pattern. Although the
      presence of glucose in the media appeared to influence positively the mineral
      penetrating abilities of the fungi, the results obtained also showed that some
      geochemical change(s) might occur under nutrient-limited conditions. It was,
      however, unclear whether the hyphae actively penetrated the minerals or were
      growing into pre-existing pores or cracks.

PMID- 15984572
TI  - Melatonin increases tissue accumulation and toxicity of cadmium in the bank vole
      (Clethrionomys glareolus).
AB  - Recent study has shown that a short photoperiod increases the accumulation and
      toxicity of cadmium (Cd) in the bank vole as compared to a long photoperiod.
      Since many of the effects of photoperiod on physiological processes in small
      mammals are transduced by the pineal gland and its hormone melatonin, in this
      study the effect of subchronic melatonin injection (7 micromol/kg/day for 6
      weeks) on the hepatic, renal and intestinal Cd accumulation in the bank voles
      raised under a long photoperiod and exposed to dietary Cd (0.9 micromol/g) was
      examined. Simultaneously, histological examinations of the liver and kidneys, and
      analyses of metallothionein (MT) and lipid peroxidation were carried out.
      Melatonin co-treatment brought about a significant increase in the hepatic (61%),
      renal (79%) and intestinal (77%) Cd concentrations as compared to those in the Cd
      alone group. However, the concentrations of MT in the liver and kidneys of the Cd
      + melatonin co-treated bank voles did not differ from those in the Cd alone
      group. Also, histopathological changes in the liver (infiltration of leukocytes)
      and kidneys (glomerular swelling and a focal tubular cell degeneration) as well
      as an increase (2-fold) in the renal lipid peroxidation occurred only in animals
      from the Cd + melatonin group. These data indicate that (1) subchronic melatonin
      injection has similar effect on the tissue accumulation and toxicity of Cd to
      that produced by a short photoperiod and (2) the Cd-induced toxicity in the liver
      and kidneys of melatonin co-treated bank voles is probably due to increased Cd
      accumulation and decreased synthesis of MT.

PMID- 15984573
TI  - [G. P. Shultsev's contribution into the development of clinical medicine].

PMID- 15984574
TI  - [Modern molecular and genetic aspects in clinical gastroenterology].

PMID- 15984575
TI  - [The results of endovascular and surgical myocardial revascularization in
      patients with type II diabetes mellitus].

PMID- 15984577
TI  - [Study of the influence of vital exhaustion on myocardial infarction risk in a
      male population aged 25 to 64 years].
AB  - The aim of the study was to investigate the influence of vital exhaustion (VE) on
      the 8-year risk of myocardial infarction (MI) in men aged 25 to 64 years old. A
      random representative sample of male inhabitants of one of Novosibirsk districts,
      aged 25 to 64 years, was included in the WHO MONICA-psychosocial program. Within
      8 years (1994-2000) all the cases of MI in the cohort were studied using the WHO
      Acute Myocardial Infarction Register project. The statistical analysis was
      performed using SPSS-10 software package. The relative risk (RR) of MI was
      evaluated using a Cox proportional regressive model. The prevalence of VE in
      subjects with MI was 65.8%. The 8-year RR of MI in men aged 25 to 64 years was
      2.16 times higher (p < 0.05) in presence of VE and was the highest in widowers,
      divorced men, subjects with incomplete secondary or primary education, men of
      hard or moderate physical labor, and pensioners. The results show that RR of MYis
      associated with VE, which, in its turn, is directly related to social and
      economic status.

PMID- 15984576
TI  - [Ventricular arrhythmias and cardiac late potentials inpatients with acute
      coronary syndrome after reperfusion therapy].
AB  - The prognostic value of ventricular late potentials (VLP) and the character of
      rhythm disturbance were studied in 64 patients with acute coronary syndrome. 8
      hours after system thrombolysis procedure VLP rate increased from 68.6% up to
      85.7%. In all cases of reperfusion arrhythmia deterioration of signal-averaged
      ECG (SAECG) parameters and VLP were observed. Within the hospital treatment
      period VLP rate in the 1st group (patients receiving thrombolytic therapy) was
      lower than in the 2nd (no thrombolytic therapy). In the 1st group VLP was
      observed in 31.4% of the patients on the 10th day and in 11.4% by the end of
      hospital treatment; in the 2nd group--in 48.3% and 41.4% of the patients,
      respectively (p < 0.05). Administration of beta-adrenoblockers in both groups
      allowed improvement of SAECG parameters and cardiac rhythm variability.

PMID- 15984578
TI  - [Infective endocarditis: the features of its clinical course and the prognosis].
AB  - The paper covers an investigation of 150 patients with infective endocarditis
      (IE), including 100 patients (aged 18 to 30 years old) with intravenous drug
      abuse as the main risk factor. This subgroup is characterized by an acute
      clinical course of IE, with tricuspid valve disorder in most cases and septic
      pulmonary embolism relapse in 72% of cases. Heart failure, multiple cardiac
      valvular disorder and focal lung destruction were found to be the main factors of
      unfavorable outcome. A relation between the size of vegetation on the heart
      valves and the mortality rate was established. At the same time, secondary
      immunodeficiency due to HIV-infection had no significant effect on the mortality
      rate in the group of drug addicts. More frequent cases of heart failure with
      systemic circulation embolism lead to higher hospital mortality in the group of
      patients with a subacute clinical course of IE. In elderly patients other
      concomitant pathology resulted in late IE detection and a high mortality rate.

PMID- 15984579
TI  - [Photoperiodism and brain strokes in years with low and high solar activity].
AB  - The paper demonstrates substantial (p = 0.95) increase of brain stroke (BS) rate
      during daylight hours, compared with that in the night-time hours. Such pattern
      is observed in accordance with astronomic seasons, half-year and year intervals:
      1996 was a year with low solar activity (YLSA), 2000--a year with high solar
      activity (YHSA). Between the seasons "morning" and "day" during daylight hours
      and the seasons "night" and "day" in the night-time hours in YLSA the study
      revealed two biological turning-points, depending on the natural day length. In
      YHSA BS rate was the same in different seasons both during daylight hours and in
      the night-time hours. The variation of the BS rate within 24-hour time intervals
      demonstrates that the reference rate of Smolensk inhabitants for BS is season
      dependent in YLSA, in comparison with that in YHSA; it is the highest in the
      seasons "morning" and "night" and the lowest in the seasons "evening "and "day".
      There is a weak correlation between BS rate and the physical phenomena under
      study (light and darkness). The results demonstrate possible direct biotropic
      effect of the light--darkness shift on BS rate in YLSA.

PMID- 15984580
TI  - [A NSAID-associated alimentary tract disease in patients with rheumatism in
      Russia].
AB  - The aim of the study was to evaluate the prevalence and character of non-steroid
      antiinflammatory drug (NSAID)-associated pathology in patients with rheumatic
      diseases (RD) in the Russian population. The study included questioning of 2537
      RD patients (81% women and 19% men, mean age 55.8 +/- 14.2 years) who were taking
      NSAID, in 6 regions of Russia, between the October of 2003 and April of 2004. The
      results were analyzed using chi2 criterion, Fisher exact test, and Student t
      criterion. 7.6% of the questioned and 14.7% of their relatives had ulcerous
      background [corrected] history (ulcers diagnosted prior to the beginning of
      treatment with NSAID). Most patients (70.1%) were taking non-selective NSAID
      (NSNSAID), chiefly diclophenac (50.9%). The most often used non-selective
      cyclooxygenasa-2 (COG-2) inhibitor was nimesulid, taken by 23.5% of the patients.
      20.2% of patients were not aware of the influence of NSAID on the gastric and
      intestinal mucosa. 33.7% of the patients underwent esophagogastroduodenoscopy
      (EGDS) while taking NSAID. In 8.8% of the examined gastric or duodenal ulcers
      were found while they were taking NSAID; 1.5% of the examined developed gastro
      duodenal hemorrhage or ulcer perforation. 53.1% of the questioned had
      gastroduodenal complaints; in most cases it was heartburn (37.3%), "heaviness" in
      the epigastral area (37.4%), and meteorism (37.4%). 51.3% of the patients
      associated gastroesopagial reflux and dyspepsia symptoms with intake of NSAID.
      26.9% of the questioned associated stool disturbances and meteorism with NSAID
      intake. 32% of the patients took medications to eliminate gastrointestinal
      disorder symptoms. Patients taking selective COG-2 inhibitors had complaints less
      frequently than those who were taking NSNSAID (p = 0). Most frequently complaints
      were associated with intake of glucocorticoids (p = 0), low doses of aspirin (p =
      0), smoking (p = 0), and elderly age (p = 0.007). Appearance of complaints was
      not associated with the dose of NSAID (diclophenac) (p = 0.257). 8.8% of the
      patients with ulcerous background were not aware of the effects of NSAID on the
      alimentory tract; 34.1% of the patients din not undergo EGDS withing the period
      of treatment with NSAID. Only 40.3% of patients were taking selective COG-2
      inhibitors; 54.7% of patients were taking gastroprotective preparations.
      Alimentary tract pathology is a prevalent complication of therapy with NSAID in
      the Russian population. The most frequent gastrointestinal symptoms are
      subjective; they affect life quality substantially. Their risk factors are:
      elderly age, ulcer background, and glucocorticoid intake. Russian doctors do not
      take sufficient measures to prevent serious NSAID intake complications.

PMID- 15984581
TI  - [Lipid peroxidation and anti-oxidative protection in patients with chronic type C
      hepatitis].
AB  - The aim of the work was to study lipid peroxidation (LP) activity and
      antioxidation protection sufficiency in patients with HCV lesion of the liver.
      The subjects of the study were 238 such patients, divided into groups according
      to the degree of the pathological process severity. The results demonstrate a
      significant increase of malonic dialdehyde (MDA) serum concentration (up to
      143.75%) and simultaneous decrease of catalase serum concentration in patients
      with minimal activity of HCV chronic hepatitis (CH). In patients with moderate
      and high activity of the pathological process MDA serum concentrations were 150
      and 175%, respectively; catalase activity decreased down to 64.8 and 58.47%,
      respectively. Hepatocirrhosis in HCV patients (HCV-H) was characterized by a more
      pronounced LP product accumulation and decrease of serum catalase activity. MDA
      serum concentration in patients with mixed viral CH and hepatocirrhosis was lower
      than in patients with HCV-H.

PMID- 15984582
TI  - [The features of uric acid metabolism in women in climacterium].
AB  - The purpose of the study was to establish the prevalence of uric acid (UA)
      metabolism disturbances as a possible risk factor of urate nephropathy in women
      of various age groups. The authors carried out a retrospective analysis of 757
      case histories and performed uricemia and uricosuria screening in women aged 18
      to 69 years. The study revealed significant age-dependent elevation of uricemia,
      with hyperuricemia (HUE) at the age of 60 to 69 years old. The study also found
      age-dependent increase of HUE rate with its significant elevation in
      postmenopausal women (older than 50 years), compared with HUE rate in
      reproductive age women (18 to 49 years old) -37.9% vs. 11.4%. For the first time
      the researchers established UA excretion level and found a significant tendency
      of uricosuria to decrease with age (p < 0.016 between the groups of 40 to 49 and
      50 to 59 years old). The highest rate of hyperuricosuria was revealed in women of
      40 to 49 years old (22.2%), while in women of 18 to 29 and 60 to 69 years old it
      was 10.1% to 12.1%. For the first time the authors established the rate of
      hypouricosuria in women, which culminated in women older than 50 (22% of cases).
      The increase of HUE rate, which is most prominent in postmenopausal women, is
      associated with the decrease in UA excretion, accompanied by the decrease of
      hyperuricosuria rate and increase of hypouricosuria rate. Taking into account
      high prevalence of UA metabolism disturbances in women older than 50, menopause
      may be considered a risk factor of HUE and urate nephropathy.

PMID- 15984583
TI  - [Anti-phosphatidylethanolamine antibodies in patients with Sneddon's syndrome].
AB  - Anti-phosphatidylethanolamine antibodies (aPE) belong to the group of anti
      phospholipid antibodies (aPL) and are directed against neutral phospholipid,
      connected with co-factor protein, while cardiolipin antibodies (aKL) are directed
      against negative phospholipid. The paper presents a study of prevalence and
      clinical significance of IgG aPE in 28 patients (22 women and 6 men, mean age
      47.6 +/- 11.6 years) with Sneddon's syndrome (SS), which consists in
      cerebrovascular disturbances and extensive livedo reticularis. IgG aPE were
      detected by immune-enzyme assay. The upper normal limit, calculated as mean + 3SD
      after studying 19 healthy donors, was 0.303 optic density units. aPE were found
      in 15 (54%), aKL and/or lupus anticoagulant (LA)--in 6 (21%) patients with SS.
      aPE were found in 10 (46%) out of 22 aKL- and LA-negative patients. Among the aPE
      positive patients there was a higher incidence of cortic dementia (53% vs. 8%, p
      = 0.02), the widening of cortical sulci, detected by means of computed tomography
      and magnetic resonance imaging (73% vs. 31%, p = 0.05), and mild renal syndrome
      (73% vs. 16%, p = 0.03). Besides, they displayed a higher rate of headaches (87%
      vs. 62%), chorea (33% vs. 8%), epilepsy (27% vs. 8%), non-carrying of pregnancy
      (91% vs. 50%), peripheral venous thrombosis (27% vs. 15%), coronary heart disease
      (47% vs. 31%), cardiac valvular thickening, detected by means of EchoCG (93% vs.
      69%), arterial hypertension (87% vs. 54%), thrombocytopenia (20% vs. 0), anemia
      (40% vs. 15%); however, the difference was not significant. The results show that
      aPE detection, performed in addition to detection of classic immunological
      antiphospholipid syndrome markers (aKL and LA), increases the portion of aPE
      positive patients with SS by 33%. aPE are often (in 46% of cases) found in aKL-
      and LA-negative patients with SS. aPE is likely to be the most significant factor
      of thrombosis in small arteries of the brain cortex and kidneys, which could
      explain their association with dementia and renal syndrome.

PMID- 15984584
TI  - [Treatment of hypertensic crises].
AB  - The paper deals with application of modern medicines (ebrantil, dalargin, dilzem
      retard, nematop, enalapril) for treatment of hypertensic crisis, and the authors'
      experience in application of the antioxidative agent mexicor in complex therapy
      of this disorder.

PMID- 15984585
TI  - [Efficacy of conventional mono mac therapy and mono mac chronotherapy of painless
      myocardial ischemia in patients with insulin-independent diabetes].
AB  - 60 patients, suffering from coronary heart disease with painless myocardial
      ischemia (PMI) and insulin-independent diabetes (IID), were randomized into two
      groups. The first group included 18 patients, who received conventional mono mac
      therapy in a dose of 20 mg twice a day, the second--42 patients, whose treatment
      consisted in mono mac chronotherapy, i.e. they were administered a single dose of
      10 to 20 mg of the drug 30 minutes before a PMI episode, revealed by means of
      Holter ECG-monitoring, before the beginning of the treatment. All the patients
      underwent examination, which consisted in Holter ECG-monitoring and Echo-CG,
      before and after a 15-day mono mac therapy course and adequate IID treatment. The
      study demonstrated that the total length and number of PMI episodes within a 24
      hour interval, as well as the average episode length, were significantly less in
      the second group, compared with conventionally treated patients. The
      chronotherapy allowed a 2-fold reduction in mono mac doses.

PMID- 15984586
TI  - [Clinical manifestation of Churg-Strauss disease].

PMID- 15984587
TI  - [Difficulties in diagnostics of acute abdominal vascular diseases].
AB  - The article discusses difficulties in diagnostics of some acute vascular diseases
      of abdominal organs, associated with abdominal pain. The analysis of the reasons
      for late diagnosis of mesenterial thrombosis and dissecting aneurysm of the
      abdominal aorta is based on 2 clinical observations.

PMID- 15984588
TI  - [A case of electrodeinduced endocarditis].

PMID- 15984589
TI  - [A clinical case of dirofilariasis].

PMID- 15984590
TI  - Medicago sativa.

PMID- 15984591
TI  - The role of leukotrienes in allergic rhinitis.
AB  - OBJECTIVE: To review the role of cysteinyl leukotrienes (cysLTs) in allergic
      rhinitis and the scientific rationale for therapy with leukotriene receptor
      antagonists (LTRAs). DATA SOURCES: Relevant basic science and clinical articles
      were identified by a search of the PubMed database for articles published from
      1984 to 2004 using the following keywords: allergic rhinitis; nose; immune
      response; allergen challenge; leukotrienes C, D, and E; cysteinyl leukotriene;
      cysteinyl leukotriene receptor; cytokine; leukocyte; montelukast; zafirlukast;
      and pranlukast. STUDY SELECTION: The authors' expert opinion was used to select
      studies for inclusion in this review. RESULTS: CysLTs are synthesized via 5
      lipoxygenase metabolism of arachidonic acid by mast cells and basophils during
      the early-phase response to antigen and by eosinophils and macrophages during the
      late phase. The cysLT levels in nasal secretions are elevated after short-term
      allergen instillation and in allergy season in patients with allergic rhinitis.
      These lipid mediators act locally and systemically by interacting with receptors,
      particularly the cysLT1 receptor, on target cells. Evidence derived from topical
      application of cysLTs in the nose and from the effects of LTRAs indicates that
      cysLTs contribute to nasal mucous secretion, congestion, and inflammation. CysLTs
      promote allergic inflammation by enhancing immune responses and the production,
      adhesion, migration, and survival of inflammatory cells such as eosinophils. They
      also increase the generation of an array of other proinflammatory mediators, such
      as cytokines, which in turn increase the production of and receptors for cysLTs.
      Clinical trials have demonstrated that LTRAs have significant but modest efficacy
      as single agents but additive efficacy when used with other classes of agents.
      CONCLUSIONS: CysLTs fulfill the criteria for relevant mediators of allergic
      rhinitis via their diverse effects on immune, inflammatory, and local structural
      components of disease. By blocking the cysLT1 receptor responsible for most of
      these effects, LTRAs represent a useful approach to treatment of this important
      and prevalent disorder.

PMID- 15984592
TI  - Food intolerance, flushing, and diarrhea in a 44-year-old woman.

PMID- 15984593
TI  - Role of intradermal skin tests in the evaluation of clinically relevant
      respiratory allergy assessed using patient history and nasal challenges.
AB  - BACKGROUND: Skin testing, correlated with patient history, is the accepted method
      of identifying clinically relevant aeroallergen sensitivity. Traditionally,
      intradermal tests are believed to be more sensitive in identifying aeroallergen
      sensitivity than the epicutaneous and percutaneous methods. Therefore, many
      allergy practitioners use the epicutaneous or percutaneous method first and, if
      the results are negative, follow up with intradermal tests. OBJECTIVES: To
      compare the epicutaneous, percutaneous, and intradermal methods to determine
      their sensitivity to patient history and to evaluate the value of intradermal
      tests when epicutaneous and percutaneous test results are negative. METHODS:
      Participants were evaluated for rhinoconjunctivitis symptoms and then were skin
      tested using the prick and Multi-Test II (MTII) methods. Intradermal tests were
      performed when prick and MTII test results were negative to an aeroallergen.
      Participants with negative prick and MTII test results and corresponding positive
      intradermal test results underwent nasal challenges with evaluation by anterior
      rhinomanometry. RESULTS: Compared with patient history, average sensitivity for
      MTII was 77% and for the prick method was 62%. When MTII results were negative,
      17% of intradermal tests corresponded with probable patient histories of allergy
      but none with positive nasal challenge results. Nasal challenge results were
      similar to those of the negative control group and significantly different from
      those of the positive control group (P < .001). CONCLUSIONS: The MTII tests are
      more sensitive and equally specific compared with the prick method. When MTII
      results are negative, positive intradermal test results are unlikely to identify
      clinically relevant aeroallergen sensitivity. Routine performance of intradermal
      tests when MTII results are negative is likely to be of low clinical yield.

PMID- 15984594
TI  - Changes in asthma prevalence and impact on health and function in Seattle middle
      school children: 1995 vs 2003.
AB  - BACKGROUND: The prevalence of asthma has increased during the past several
      decades but may have stabilized during the last 5 years. It is not known whether
      the functional and health impact of asthma has decreased during the past decade.
      OBJECTIVE: To evaluate changes during a recent 8-year period in the prevalence
      and health and functional impact of current asthma symptoms in young teenagers.
      METHODS: In 1995 and 2003, 2,330 and 2,397 middle-school students from Seattle,
      WA, respectively (median age, 13 years), completed written surveys and answered
      questions pertaining to 4 wheezing or asthma video scenarios. Children were
      categorized as having physician-diagnosed current asthma (wheeze in the past year
      and a physician diagnosis of asthma), undiagnosed current asthma symptoms (wheeze
      in the past year without a physician diagnosis), or no asthma. Outcome measures
      were the prevalence of asthma and undiagnosed asthma symptoms and the differences
      between years in respiratory-associated functional impairment (exercise
      limitation, missed school, disrupted sleep) and health impact (physician visits,
      wheeze-limited speech). RESULTS: The prevalence of physician-diagnosed current
      asthma increased from 1995 to 2003 (3.0% to 6.2%), whereas that for undiagnosed
      current asthma symptoms decreased (12.0% to 6.2%). The degree of functional and
      health impairment was similar between the 2 study periods for each subgroup and
      was highest in the children with physician-diagnosed current asthma. CONCLUSIONS:
      The prevalence of current asthma symptoms in middle-school children from Seattle
      decreased slightly between 1995 and 2003, whereas the diagnosis of asthma
      increased. However, the health and functional impact of asthma did not diminish.
      Asthma is being diagnosed more often, but many children with asthma are still not
      achieving good asthma control.

PMID- 15984595
TI  - Quality of life and polysensitization in young men with intermittent asthma.
AB  - BACKGROUND: Health-related quality of life (HRQoL) represents an important
      variable in asthma management. To date, to our knowledge, no study has explored
      the relationship between HRQoL and sensitization in patients with asthma.
      OBJECTIVE: To evaluate the relationships among HRQoL and sensitization, pulmonary
      function, and bronchial hyperreactivity in a group of young men with intermittent
      asthma. METHODS: We studied 185 conscripts with intermittent asthma and bronchial
      hyperreactivity. The Asthma Quality of Life Questionnaire was used. Skin prick
      testing, spirometry, and methacholine challenge were performed in all
      participants. RESULTS: The Asthma Quality of Life Questionnaire median scores
      were greater than 4, indicating suboptimal HRQoL. Polysensitization was
      significantly associated with the worst HRQoL, whereas pulmonary function and
      bronchial hyperreactivity category were not. CONCLUSIONS: This study provides the
      first evidence that HRQoL is associated with polysensitization in intermittent
      asthma and underlines the importance of evaluating this issue when managing young
      patients with slight respiratory symptoms.

PMID- 15984596
TI  - Association of active and passive smoking with allergic disorders in pregnant
      Japanese women: baseline data from the Osaka Maternal and Child Health Study.
AB  - BACKGROUND: Evidence remains inconclusive as to whether smoking is a risk factor
      for allergic disorders in adults. OBJECTIVE: To investigate the relationship
      between active and passive smoking exposure and allergic disorders in pregnant
      Japanese women. METHODS: This cross-sectional study included 1,002 pregnant
      women. Participants were classified as having asthma after the age of 18 years if
      they had used an asthma medication at any time after reaching the age of 18
      years. Current atopic eczema and allergic rhinitis (including cedar pollinosis)
      were defined as being present if participants had received any drug treatment
      during the previous 12 months. Adjustment was made for age; gestation; parity;
      family history of asthma, atopic eczema, and allergic rhinitis; indoor domestic
      pets; family income; education; and the mite antigen level in house dust.
      RESULTS: Current smoking, but not environmental tobacco smoke exposure, was
      independently related to an increased prevalence of asthma after the age of 18
      years (adjusted odds ratio [OR], 2.66; 95% confidence interval [CI], 1.30-5.38).
      A significant positive association of current passive smoking exposure at home
      (adjusted OR, 1.89; 95% CI, 1.10-3.30) and at work (adjusted OR, 2.50; 95% CI,
      1.29-4.76) with the prevalence of current allergic rhinitis was observed, whereas
      no measurable association with active smoking exposure was found. Neither active
      nor passive smoking was statistically significantly related to the prevalence of
      current atopic eczema. CONCLUSIONS: These findings suggest that active smoking
      and environmental tobacco smoke exposure may increase the likelihood of asthma
      and allergic rhinitis, respectively, in pregnant Japanese women.

PMID- 15984597
TI  - Chronic hyperplastic eosinophilic sinusitis as a predictor of aspirin-exacerbated
      respiratory disease.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a disease of
      intense eosinophilic inflammation that can produce fibrosis, hyperplasia, and
      remodeling. OBJECTIVE: To investigate the usefulness of quantifying severity of
      chronic hyperplastic eosinophilic sinusitis in predicting the presence of AERD.
      METHODS: Data were compared between asthmatic patients who reported exacerbations
      after aspirin ingestion and those who did not. The primary outcome measure was
      severity of sinusitis using a validated computed tomography (CT) scan-based
      scoring system. Indices of lower airway remodeling and other markers of
      inflammation were also evaluated. RESULTS: Twenty-one patients with AERD were
      compared with 19 patients with aspirin-tolerant asthma (ATA). Patients were well
      matched for asthma severity as shown by their similar lung function as measured
      by postbronchodilator forced expiratory volume in 1 second. Patients with AERD
      were distinguished by their sinus CT scores (AERD patients: 16.9; 95% confidence
      interval [CI], 13.4-21.3; ATA patients: 6.2; 95% CI, 4.2-9.1; P < .001), and they
      were considerably more likely to have nasal polyps (AERD patients: 90%; ATA
      patients: 26%; P < .001). In addition, AERD patients demonstrated increased total
      lung capacity (AERD patients: 107.9%; 95% CI, 99.9%-117.6%; ATA patients: 98.0%;
      95% CI, 93.7%-102.5%; P = .05), reflecting a trend toward increased air trapping.
      No significant differences occurred in diffusing capacity, exhaled nitric oxide,
      eosinophilia, or exhaled breath condensate pH. CONCLUSIONS: AERD can be
      distinguished from ATA by the extent of hyperplasia on CT scan and the presence
      of nasal polyps. We hypothesize that AERD represents a remodeling process that
      affects both the upper and lower airways.

PMID- 15984598
TI  - Mite and pet allergen exposure in Brazilian private cars.
AB  - BACKGROUND: The role of mite and pet allergens in the development of allergic
      diseases has been recognized for many years. OBJECTIVE: To determine mite
      (Dermatophagoides pteronyssinus [Der p 1] and Dermatophagoidesfarinae [Der f 1]),
      cat (Felis domesticus [Fel d 1]), and dog (Canis familiaris [Can f 1]) allergen
      levels in Brazilian private cars. METHODS: Mite, cat, and dog allergens were
      measured in dust samples collected from 60 upholstered seats of private vehicles
      using enzyme-linked immunosorbent assays. RESULTS: Mean levels of Der p 1 (0.24
      microg/g of dust; range, 0.06-2.05 microg/g of dust) and Der f 1 (0.29 microg/g
      of dust; range, 0.06-2.07 microg/g of dust) were extremely low in most dust
      samples analyzed. In contrast, sensitizing mean levels of Can f 1 (1.51 microg/g
      of dust; range, 0.14-30.96 microg/g of dust) and Fel d 1 (0.43 microg/g of dust;
      range, 0.02-5.75 microg/g of dust) were observed in 32 (53%) and 12 (20%)
      samples, respectively. Mean Can f 1 levels were significantly higher in cars
      whose owners kept dogs at home (3.27 microg/g of dust) than in those without pets
      (0.57 microg/g of dust; P = .008). There were no significant differences in
      allergen levels regarding the age of the vehicle or the number of users and
      whether the owners transport pets inside the vehicles. CONCLUSIONS: Private cars
      constitute an important pet, but not mite, allergen reservoir for continuous
      contamination of the indoor environment. Pet allergens may be present even in
      cars whose owners do not have pets. Effective measures to reduce allergen
      exposure in cars should be taken routinely, especially for pet-allergic patients.

PMID- 15984599
TI  - Once-daily fexofenadine treatment for chronic idiopathic urticaria: a
      multicenter, randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Chronic idiopathic urticaria (CIU) can have a profound effect on
      patients' health and quality of life. OBJECTIVE: To evaluate the efficacy and
      safety of once-daily dosing of fexofenadine hydrochloride, 180 mg, on CIU.
      METHODS: This randomized, double-blind, parallel-group, placebo-controlled study
      consisted of a placebo run-in period followed by a 4-week treatment period.
      Patients 12 years and older with active CIU were randomized 2:1 to receive once
      daily fexofenadine, 180 mg, or placebo. The primary end points were change from
      baseline in mean daily number of wheals (MNW score) and mean daily severity of
      pruritus during treatment. Secondary efficacy measures included modified total
      symptom scores and MNW and pruritus severity scores evaluated weekly and
      instantaneously at trough drug levels. RESULTS: Patients administered
      fexofenadine (n = 163) experienced significantly greater improvements in MNW and
      pruritus severity scores compared with the placebo group (n = 92) (P < .001 for
      both). Similarly, throughout treatment and at each individual week, the mean
      reductions in modified total symptom scores were significantly greater in the
      fexofenadine group (P < or = .005 for all comparisons vs placebo). The mean
      reductions in instantaneous MNW and pruritus severity scores were greater in
      patients in the fexofenadine group than in those who received placebo (MNW score:
      P = .015; pruritus severity score: P < .001). There were no significant
      differences in the frequency of treatment-emergent adverse events between the 2
      treatment groups. CONCLUSIONS: A once-daily dose of fexofenadine hydrochloride,
      180 mg, offered effective, well-tolerated relief for the management of CIU.

PMID- 15984600
TI  - Effect of montelukast on nuclear factor kappaB activation and proinflammatory
      molecules.
AB  - BACKGROUND: Montelukast is known as a cysteinyl leukotriene 1 receptor
      antagonist. However, the action of montelukast in terms of nuclear factor KB (NF
      kappaB) activation and the production of proinflammatory molecules is unknown.
      OBJECTIVE: To demonstrate the potential anti-inflammatory effect of montelukast.
      METHODS: We examined whether montelukast inhibits the activation of NF-kappaB, a
      transcription factor that regulates the expression of proinflammatory molecules.
      The inhibitory effects of montelukast on tumor necrosis factor kappa (TNF-kappa)-
      induced NF-kappaB activation on THP-1 cells, a human monocytic leukemia cell
      line, were evaluated by flow cytometry, and those on lipopolysaccharide-induced
      interleukin 1beta (IL-1beta), IL-6, TNF-alpha, and monocyte chemoattractant
      protein 1 (MCP-1) production in peripheral blood mononuclear cells were evaluated
      by enzyme-linked immunosorbent assay. RESULTS: Flow cytometry demonstrated that
      montelukast inhibited NF-kappaB activation in THP-1 cells in a dose-related
      manner. Furthermore, 10(-5)M montelukast significantly inhibited
      lipopolysaccharide-induced IL-6, TNF-alpha, and MCP-1 production in the
      peripheral blood mononuclear cells of controls and patients with asthma.
      Lipopolysaccharide-induced IL-1beta production was not inhibited by montelukast.
      CONCLUSIONS: These findings suggest that high doses of montelukast modulate the
      production of IL-6, TNF-alpha, and MCP-1 through the inhibition of NF-kappaB
      activation. However, the anti-inflammatory effect of montelukast at therapeutic
      doses in patients with asthma needs to be further investigated.

PMID- 15984601
TI  - Dose-response comparison of budesonide dry powder inhalers using adenosine
      monophosphate bronchial challenge.
AB  - BACKGROUND: Bronchial hyperresponsiveness to adenosine monophosphate, an indirect
      measure of airway inflammation, is a sensitive marker of inhaled corticosteroid
      efficacy. OBJECTIVE: To evaluate the relative therapeutic efficacy of budesonide
      delivered via Clickhaler and Turbuhaler dry powder inhalers in patients with mild
      to-moderate persistent asthma. METHODS: In a double-masked, dose-response
      crossover study, 27 patients received inhaled budesonide in cumulative sequential
      doubling dose increments, 2 weeks per dose, of 200, 400, and 800 microg/d. Each
      treatment block was preceded by 1- to 3-week placebo run-in and washout periods.
      End points were measured after each placebo (ie, baseline) and treatment period.
      Adenosine monophosphate bronchial challenge was the primary outcome, and exhaled
      nitric oxide, serum eosinophilic cationic protein, spirometry, domiciliary peak
      expiratory flow, symptoms, and rescue medication use were the secondary outcomes.
      RESULTS: For the adenosine monophosphate provocation concentration that caused a
      decrease in forced expiratory volume in 1 second of 20% (PC20), a significant
      overall dose-response effect (P = .006) was found, and there was no significant
      difference between the devices (P = .8). The relative microgram dose potency
      ratio between Clickhaler and Turbuhaler was 1.11 (95% confidence interval [CI],
      0.50-2.46). After administration of the highest dose of budesonide, the mean
      doubling dilution shift in adenosine monophosphate PC20 from placebo baseline was
      3.46 (95% CI, 2.66-4.27) with the Clickhaler vs 3.41 (95% CI, 2.47-4.35) with the
      Turbuhaler. A significant overall dose-response effect was demonstrated for
      exhaled nitric oxide (P = .03) but not for any of the other secondary outcome
      measures. There were no significant differences between the devices for any of
      the outcome measures. CONCLUSION: Inhaled budesonide exhibited overall dose
      response effects on adenosine monophosphate PC20 delivered via Turbuhaler and
      Clickhaler, with no significant difference between the devices.

PMID- 15984602
TI  - Absence of oropharyngeal vaccinia virus after vaccinia (smallpox) vaccination.
AB  - BACKGROUND: With the resumption of the vaccinia (smallpox) vaccination, questions
      regarding transmission risk prompted this study to determine whether vaccinia
      virus could be detected in the oropharynx of adults recently vaccinated with
      vaccinia (smallpox) vaccine. German, Russian, and American studies on the
      oropharyngeal presence of vaccinia virus revealed conflicting results in
      different age groups. OBJECTIVE: To measure vaccinia viral particle or antigen
      presence in the oropharynx of adult health care workers after vaccination with
      vaccinia (smallpox) vaccine using viral culture and high-sensitivity assays
      (polymerase chain reaction [PCR] and electrochemiluminescence) and to determine
      whether there is an association between the presence of vaccinia virus and
      adverse reactions. METHODS: A total of 155 adults (primary vaccinees and
      revaccinees) were enrolled for 1 baseline and 5 subsequent throat swabs. The
      swabs were evaluated using viral culture, PCR, and electrochemiluminescence.
      RESULTS: Of the 155 participants, 144 had more than 2 throat swabs in the 2 weeks
      after vaccination. Of the 801 specimens evaluated, there were no positive results
      by culture, PCR, or electrochemiluminescence except in the control samples (n =
      6), which were positive by all 3 methods. CONCLUSIONS: Based on the absence of
      detectable vaccinia virus in this study population, one can be 95% certain that
      the true rate of vaccinia virus in the oropharynx of adults during the 2 weeks
      after vaccination with vaccinia (smallpox) vaccine is 0% to 3.3%. These data
      should be reassuring to the medical community and support the Advisory Committee
      on Immunization Practice guidelines that respiratory precautions are not
      necessary after vaccinia (smallpox) vaccination in healthy adults.

PMID- 15984603
TI  - Bronchial responsiveness and serum eosinophil cationic protein levels in
      preschool children with recurrent wheezing.
AB  - BACKGROUND: Bronchial hyperresponsiveness is a universally recognized phenomenon
      of asthma, and increased levels of eosinophil cationic protein (ECP) have been
      identified in the serum of patients with asthma. OBJECTIVES: To investigate
      whether enhanced bronchial responsiveness and elevated serum ECP levels are
      associated with recurrent wheezing in preschool children and to examine the
      possible relationship between these 2 variables. METHODS: We recruited 130
      children aged 4 to 6 years: 59 with at least 3 episodes of wheezing in the
      previous year (current wheezers), 38 with a documented history of wheezing before
      3 years of age but no subsequent wheezing episodes (past wheezers), and 33 who
      had never experienced wheezing (nonwheezers). The children underwent methacholine
      bronchial provocation tests using a modified auscultation method and blood
      sampling for the measurement of ECP levels. RESULTS: Current wheezers showed
      greater bronchial responsiveness than past wheezers and nonwheezers, as
      demonstrated by lower provocation concentrations that caused audible wheeze and
      lower provocation concentrations that caused a decline in oxygen saturation of at
      least 5% from baseline. Likewise, current wheezers had higher serum ECP levels
      than the other 2 groups. Among current wheezers, ECP levels showed a significant
      negative correlation with provocation concentrations that caused oxygen
      desaturation and a marginally significant correlation with provocation
      concentrations that caused audible wheeze. CONCLUSIONS: Enhanced bronchial
      responsiveness and elevated serum ECP levels are associated with recurrent
      wheezing in 4- to 6-year-old children. These results suggest that wheezing during
      preschool years may be phenotypically similar to wheezing in older children.

PMID- 15984604
TI  - A syndrome of hypoplastic sinuses, hydrocephalus, bronchiectasis, and
      hypogammaglobulinemia with functional antibody deficiency in twin girls.
AB  - BACKGROUND: A variety of syndromes are known to be associated with immune
      deficiency, some as a major part of the syndrome and some as an occasional
      finding. OBJECTIVES: To report a newly defined syndrome of hydrocephalus,
      hypoplastic sinuses, cartilaginous webbing of the bronchi, bronchiectasis, and
      hypogammaglobulinemia with functional antibody deficiency in identical twin
      girls. METHODS: Spirometry, radiography, computed tomography (CT), bronchoscopy,
      and laboratory tests were performed for diagnosis. RESULTS: A girl (twin A) was
      evaluated at the age of 7 years for chronic cough and wheeze that worsened with
      exercise. Hydrocephalus had been diagnosed a year before evaluation. She was
      treated for cough variant asthma and was lost to follow-up until the age of 10
      years. The cough had worsened progressively, and dyspnea was now apparent.
      Spirometry was consistent with reversible airway obstruction. A chest radiograph
      was suggestive of bronchiectasis. A chest CT scan showed bilateral upper lobe
      bronchiectasis. Hypogammaglobulinemia and functional antibody deficiency were
      noted. A CT scan of the sinuses revealed aplasia or severe hypoplasia of all the
      paranasal sinuses. Bronchoscopy revealed a grossly abnormal bronchial structure
      and atrophic-appearing bronchial mucosa. Twin B also had a history of
      hydrocephalus. Although she had no respiratory symptoms, chest CT revealed
      bronchiectasis, and she had obstruction on spirometry. Laboratory analysis
      revealed hypogammaglobulinemia and functional antibody deficiency. She became
      symptomatic 2 years after twin A. CONCLUSIONS: This is a newly reported syndrome
      of hydrocephalus, absent sinuses, abnormalities of the bronchi, and functional
      antibody deficiency, which initially presented as cough and wheeze.

PMID- 15984605
TI  - Heterogeneity of the IgE response to allergenic determinants of cefaclor in serum
      samples from patients with cefaclor-induced anaphylaxis.
AB  - BACKGROUND: Beta-lactam antibiotics, such as cefaclor, may cause IgE-mediated
      anaphylactic reactions. However, the clinically available serologic test has not
      been widely accepted, and the antigenic determinants of these drugs are unclear.
      OBJECTIVE: To describe 4 cases of anaphylaxis caused by cefaclor in which a
      specific IgE response to cefaclor was demonstrated. METHODS: Four patients with
      anaphylaxis to cefaclor and 35 nonatopic controls never exposed to cefaclor were
      studied. Skin tests and oral challenges with this drug were performed. The
      specific IgE response to the antigenic determinant of cefaclor-human serum
      albumin (HSA) conjugate was compared in each patient. The serum specific IgE to
      cefaclor-HSA conjugate was detected using enzyme-linked immunosorbent assay
      (ELISA). Also, ELISA inhibition studies using various concentrations of cefaclor
      HSA, HSA alone, and free cefaclor were performed, as were hapten inhibition
      studies using cefaclor, cephalexin, cefadroxil, ampicillin, ceftriaxone, and
      cefotaxime. RESULTS: Three patients showed high levels of serum specific IgE to
      cefaclor-HSA and marked inhibition patterns to free cefaclor and cefaclor-HSA
      conjugate on ELISA inhibition testing. Hapten inhibition testing in 3 individual
      serum samples showed 2 different patterns. In patient 3, significant dose
      dependent inhibitions (up to 92%) were noted with additions of free cefaclor and
      cefaclor-HSA conjugate, and lesser inhibitions (up to 74%) were noted with
      cephalexin, which shares the aminobenzyl side chain. In patients 1 and 2, marked
      dose-dependent inhibitions were noted only with additions of cefaclor-HSA
      conjugate and free cefaclor, whereas minimal inhibitions were noted with the
      other 5 compounds. CONCLUSIONS: The specific IgE response to cefaclor-HSA
      conjugate in patients with cefaclor anaphylaxis occurs against the hapten, in
      which heterogeneity of the antigenic determinant was noted to depend on the
      individual.

PMID- 15984606
TI  - [Description of the new species Anopheles artemievi sp.n. (Diptera, Culicidae)].
AB  - The paper describes the new species Anopheles artemievi belonging to a complex of
      the species maculipennis that may play an important role in the transmission of
      malaria in both the Fergana area and the Fergana valley. In terms of the
      morphological signs of imagoes, larvae, and the composition of the egg
      exochorion, the new species is the twin of An. sacharovi Favre and An. mihrtinius
      Shingarev. According to the pattern of polytene chromosomal disks, the described
      type is identical to An. maculipennis Meigen. The structure of the second
      internal transcribed spacer (ITS2) of a cluster of ribosomal genes in An.
      artemievi is species-specific and, in its nucleotide composition, differs from
      that in related species. The sequence of ITS2 in the new species has been
      registered at the GeneBank under No. AJ849886 and it is 419 p.n. The length of
      ITS2 in An. maculipennis and A. martinius is equal to 422 p.n. (AY238435) and 447
      p.n. (AJ849885), respectively. The sequences of ITS in An. artemievi and An.
      maculipennis are 91% homologous; those in An. artemievi and An. martinius are 87%
      homologous. The nucleotide composition of ITS2 in An. artemievi differs from that
      in An. maculipennis in three deletions, 1 insertion, and 18 point substitutions
      and from that in An. martinius in 12 insertions, 2 deletions, and 40 point
      substitutions. The standard-type series is as follows: Kyrghyzstan, Batkensk
      Region, Leileksky district, Alga settlement, a cowshed, 1 male-holotype, l female
      allotype. The paratypes are 2 males, 6 females.

PMID- 15984607
TI  - [Detection of a new species of Rickettsiae in the ticks of Ixodes persulcatus in
      Russia].
AB  - Genetic analyses (polymerase chain reaction and nucleotide sequence test) have
      been used to describe a new species of Rickettsiae in the ticks Ipersukarus in
      Russia. This species is named as Rzckettsia tarasevichiae after Academician of
      the Russian Academy of Medical Sciences Irma Vladimirovna Tarasevich, Head of the
      Laboratory of Rickettsial Ecology, N.F.Gamaleya Research Institute of
      Epidemiology and Microbiology. A total of 317 Ipersukatus imagoes were collected
      in the regions of the Urals, Western Siberia, Eastern Siberia, and Far East in
      the spring of 2001 and 2002. The authors detected R. tarasevichiae in 25.5 +/-
      2.4% (87/317) of the examined I. persulcarus ticks, from 3.8% in the Novosibirsk
      Region (Western Siberia) to 56.8% in the Primorye Territory (the Far East). This
      is the first detection of the Rickettsiae in the ticks of the genus Ixodes in
      Russia. Conceivably, the spread of this Rickettsia species coincides with the
      area of I. persulcatus that inhabits the biotopes of southern taiga and mixed
      forests in Eurasia from the western frontier of Russia to the Far East. The
      nucleotide sequences of the fragments of gene 165 of pRNA and citrate synthctase
      of this species of Rickettsiae have been declared at the GenBank under numbers
      AF503168 and AF503167, respectively. Its most phylogenetically close species of
      Rickettsiae R. canadenss (69% homology in terms of the gene of citrate synthetase
      and 98% homology in terms of gene 165 of pRNA) which is responsible for cases of
      acute cerebral vasculitis in Northern America. This requires further studies of a
      possible role of R. tarasevichiae in the pattern of tick-borne infections
      recorded in the area of I. persulcatus.

PMID- 15984608
TI  - [Genetic characteristics of human pathogenic Borrelia isolated from Ixodes
      trianguliceps Bir. and Ixodes pavlovskyi Pom].
AB  - To support the results of typing the amplicon of the spacer site 5S-23S of pRNA
      by restriction fragment length polymorphism (RFLP) assay, the isolates from the
      ticks I. trianguliceps and I. pavlovskyi underwent sequenation of rrf (5S)-rrl
      (23S) spacer to make a comparative analysis of derived nucleotide sequences with
      the DDBJ/EMBL/ GenBank databases. For this purpose, the authors used six isolates
      (three imago and three nymphal) from I. trianguliceps and three isolates from
      adult hungry I. pavlovskyi females from the Borrelia museum of the Laboratory of
      Infection Transmitters, N. F. Gamaleya Research Institute of Epidemiology and
      Microbiology, Russian Academy of Medical Sciences. In the natural foci of the
      Perm Region, in the tick I. trianguliceps the same genetic variants of B. afzelii
      VS461 and B. garinii NT29 was found to occur as in I. persulcatus and small
      mammals, the reservoir Borrelia hosts. Borreliae previously detected in the tick
      I. pavlovskyi belong to B. garinii 20047.

PMID- 15984609
TI  - [Ixodes ticks of the town of Cherkessk and its environs].
AB  - The paper presents the results of the studies made in 2002-2004 to examine the
      species-specific composition of Ixodes ticks. The ticks were gathered for a flag
      (155km routes being covered and 405 ticks being gathered); 48 dogs were examined,
      320 ticks being gathered; 212 ticks were collected from human beings. The town
      dwellers' visit rates were grouped by ages and months. In the republic,
      Borreliae, the causative agents of Lyme borreliosis, were first isolated from
      Ixodes ricinus by darkground microscopy. Thus, there is one more available Lyme
      borreliosis focus. Enzyme immunoassay was used to study the sera from the
      dwellers bitten by ticks. Anti-M and anti-G antibodies were isolated. The paper
      presents the distribution of Ixodes ticks gathered for the flag and taken from
      dogs in accordance with the biotopes, establishes seasonal variations, and
      provides calculations of the abundance index on the dogs.

PMID- 15984610
TI  - [Description of the unusual course of dirofilariasis].

PMID- 15984611
TI  - [Intestinal and extraintestinal amebiasis: clinical notes].

PMID- 15984612
TI  - [The clinical characteristics of trichinosis in children].

PMID- 15984613
TI  - [P. falciparum antigens at different stages of a parasitic cycle].

PMID- 15984614
TI  - [Serological diagnosis of pneumocystosis in the population of the Republic of
      Armenia].
AB  - Serological investigations were first conducted in apparently healthy children
      and adults for pneumocyctosis in the Republic of Armenia in 2001-2004. The
      investigations provided evidence for that some of them were found to have
      antibodies to Pneumocystis carinii, which is indicative of the circulation of the
      pathogen of P. carinii infection among the population of Armenia. There were high
      serological affliction rates of P. carinii among the population in the Republic
      of Armenia, which shows it necessary to make a detailed immunological examination
      in order to study the epidemiology of this infection.

PMID- 15984615
TI  - [Preparation of a dry red blood cell Trichinella antigenic diagnosticum for
      indirect hemagglutination test and evaluation of its efficiency].
AB  - The present paper presents the stages of a process for manufacturing a dry red
      blood cell Trichinella antigenic diagnosticum for indirect hemagglutination test
      (IHAT) and the evaluation of its diagnostic efficiency. The diagnosticum is shown
      to be a 3% suspension lyophilized from formalinized and tanned sheep red blood
      cells on which an excretory-secretory antigen of invasion Trichinella larvae was
      absorbed in a dose of 100 mg/ml. The rather high sensitivity (98.7%) and
      specificity (97.3%) of IHAT using the Trichinella diagnosticum based on the
      excretory-secretory antigen allow it to be considered an effective method for
      diagnosis of human trichinosis.

PMID- 15984616
TI  - [Long-term helminthiasis control practice in the mountain areas of Daghestan].

PMID- 15984617
TI  - [Treatment of intestinal helminthiasis with albendazole].

PMID- 15984618
TI  - [Efficiency of mass dehelminthization in enterobiosis].

PMID- 15984619
TI  - [The new agent IMP-1524: design, acute toxicity, and antihymenolepidous
      activity].

PMID- 15984620
TI  - [The affection of the population with Borrelia and the incidence of Lyme
      disease].
AB  - The proportion of Lyme borreliosis seropositive residents in a number of Russia
      is 1-2 thousand times greater than that of officially notified patients. It is
      suggested that due to the ability of Lyme borreliosis to manifest in the late
      periods after infection, the time and chronicity of the infection, the number of
      officially recorded patients may significantly increase due to the manifestation
      of the disease in seropositive apparently healthy (at the moment of an
      examination) dwellers. There is evidence for that it is expedient to follow up
      seropositive residents and tick-bitten individuals.

PMID- 15984621
TI  - [Use of homeopathic drugs for the treatment of cutaneous leishmaniasis].

PMID- 15984622
TI  - [Bartonellosis and a possible role of Ixodes ticks (family Ixodidae, order
      Parasitiformes) in the transmission of pathogenic Bartonella bacteria].
AB  - The papers reviews the literature on bartonellosis and a role of Ixodes ticks,
      including the representatives of the genus Ixodes, in the circulation and
      transmission of Bartonella bacteria. It shows that man can be infected with
      pathogenic Bartonella bacteria by the bite of ticks. The paper also presents data
      on tick-transmitted human and animal mixed infections, including bartonellosis.

PMID- 15984623
TI  - [The current systematic position, spread, and variability of the biological
      variants of Echinococcus spp].

PMID- 15984624
TI  - "Counter" intuitive.

PMID- 15984625
TI  - Botanical briefs: liverworts--Frullania species.

PMID- 15984626
TI  - Tinea versicolor mimicking pityriasis rubra pilaris.
AB  - Tinea versicolor is a common noninvasive cutaneous fungal disease. We recount a
      case of tinea versicolor that mimicked type I (classic adult) pityriasis rubra
      pilaris. A 54-year-old white man reported a 20-year history of a recurrent
      pruritic eruption that had marginally improved with use of selenium sulfide
      shampoo and treatment with oral antihistamines. Results of a skin examination
      revealed erythematous plaques; islands of spared skin; and follicular
      erythematous keratotic papules on the trunk, shoulders, and upper arms. A lesion
      was scraped to obtain skin scales for potassium hydroxide staining. Examination
      of the stained samples revealed the characteristic "spaghetti and meatballs,"
      confirming the diagnosis.

PMID- 15984627
TI  - What is your diagnosis? Intramuscular hemangioma of the tongue.

PMID- 15984628
TI  - Common and uncommon hair and nail problems in sports.
AB  - We report an exhaustive review of the hair and nail conditions related to
      participation in sports. It is important that medical professionals who care for
      athletes recognize the unique dermatologic conditions that may affect those
      athletes.

PMID- 15984629
TI  - An outbreak of rat mite dermatitis in an animal research facility.
AB  - We describe an outbreak of rat mite dermatitis that affected 15 employees of an
      animal research facility. Cases of rat mite dermatitis are infrequently reported,
      and outbreaks are reported even less. Our case series demonstrates that in
      contrast to most prior outbreaks, rat mite dermatitis may occur even in modern,
      well-maintained physical surroundings and thus remains a relevant diagnosis
      today.

PMID- 15984630
TI  - Cumulative irritation potential of adapalene 0.1% cream and gel compared with
      tazarotene cream 0.05% and 0.1%.
AB  - Despite the many beneficial effects of dermatologic applications, most of the
      current treatments for acne cause local irritation. The objective of this study
      was to compare the ability of the epidermis to tolerate adapalene 0.1% cream and
      gel and tazarotene cream in concentrations of 0.05% and 0.1%. A total of 30
      subjects were enrolled in the study. The test products were applied under
      occlusive dressings at randomized sites on the upper back for approximately 24
      hours, 4 times a week, and for 72 hours, once a week, for a period of 3 weeks.
      Skin reactions (erythema score plus other local reactions) at the product
      application sites were assessed 15 to 30 minutes after dressing removal. Twenty
      six subjects completed the study. A total of 16 subjects discontinued use of 1 or
      more of the test products because of irritation scores reaching severe or
      greater; all but one of these discontinuations were at sites treated with the
      tazarotene products. The mean 21-day cumulative irritancy indices for adapalene
      0.1% cream and gel were significantly lower (P=.05) than those for tazarotene
      cream 0.05% and 0.1% and not notably higher than that of the negative control
      product.

PMID- 15984631
TI  - Perception should approximate reality.

PMID- 15984632
TI  - The licensure mobility experience within the United States.

PMID- 15984633
TI  - InfantSEE and paraoptometry.

PMID- 15984634
TI  - Examination and vision rehabilitation treatment of the individual with vision
      impairment.

PMID- 15984635
TI  - Preparation is key when 'passing the baton'.

PMID- 15984636
TI  - Midwives: professional servants?

PMID- 15984637
TI  - Benefits of birth centres.

PMID- 15984638
TI  - Social exclusion: parents with learning disabilities.

PMID- 15984639
TI  - One year on ... as busy as ever.

PMID- 15984640
TI  - Chinese whispers: impressions of Shanghai.

PMID- 15984641
TI  - Registration of stillbirths and certification for pregnancy loss before 24 weeks'
      gestation.

PMID- 15984642
TI  - Midwifery reborn: opportunities for the new generation.

PMID- 15984643
TI  - Leading the midwifery renaissance.

PMID- 15984644
TI  - Guidelines for midwives by midwives.

PMID- 15984645
TI  - The election result--implications for midwives.

PMID- 15984646
TI  - Maternal request for caesarean section.

PMID- 15984647
TI  - Disclosure of information.

PMID- 15984648
TI  - Practising real midwifery.

PMID- 15984649
TI  - Why midwives leave.

PMID- 15984650
TI  - A birth vision.

PMID- 15984651
TI  - Should male partners be present at the birth?

PMID- 15984652
TI  - The first water channel protein (later called aquaporin 1) was first discovered
      in Cluj-Napoca, Romania.
AB  - This invited review briefly outlines the importance of membrane water
      permeability, highlights the landmarks leading to the discovery of water
      channels. After a decade of systematic studies on water channels in human RBC
      Benga's group discovered in 1985 the presence and location of the water channel
      protein among the polypeptides migrating in the region of 35-60 kDa on the
      electrophoretogram of RBC membrane proteins. The work was extended and reviewed
      in several articles. In 1988, Agre and coworkers isolated a new protein from the
      RBC membrane, nick-named CHIP28 (channel-forming integral membrane protein of 28
      kDa). However, in addition to the 28 kDa component, this protein had a 35-60 kDa
      glycosylated component, the one detected by the Benga's group. Only in 1992
      Agre's group suggested that "it is likely that CHIP28 is a functional unit of
      membrane water channels". Half of the 2003 Nobel Prize in Chemistry was awarded
      to Peter Agre (Johns Hopkins University, Baltimore, USA) "for the discovery of
      water channels", actually the first water channel protein from the human red
      blood cell (RBC) membrane, known today as aquaporin 1 (AQP1). The seminal
      contributions from 1986 of the Benga's group were grossly overlooked by Peter
      Agre and by the Nobel Prize Committee. Thousands of science-related professionals
      from hundreds of academic and research units, as well as participants in several
      international scientific events, have signed as supporters of Benga; his priority
      is also mentioned in several comments on the 2003 Nobel Prize.

PMID- 15984653
TI  - The interaction between the cholinergic and dopaminergic system in learning and
      memory process in rats.
AB  - In normal rats, muscarinic acetylcholine receptors (mAChRs) have a facilitating
      role on both short-term and long-term memory tested by Y-maze task and multi
      trial passive avoidance test, respectively, since scopolamine, a specific mAChRs
      antagonist, impairs both types of memory. A low dose of nicotine (0.3 mg/kg b.w.,
      i.p.), a specific nicotinic acetylcholine receptors (nAChRs) agonist,
      administered once caused a significant facilitating effect on short-term memory.
      A higher dose of nicotine (3 mg/kg b.w., i.p.) administered 5 consecutively days
      had about the same facilitating effect on short- and long-term memory without
      affecting information acquisition. In rats, having mAChRs and nAChRs blocked by
      means of scopolamine and chlorisondamine respectively, a low dose of nicotine
      administered once caused a significant improvement of long-term memory deficits
      without affecting significantly short-term memory. A higher dose of nicotine
      administered 5 consecutive days in rats with a double blockade of cholinergic
      receptors had the same ameliorating effect on long-term memory deficits as low
      dose. Our data suggest that the antiamnesic effect of nicotine can result from an
      action at nicotinic receptors subtypes not blocked by chlorisondamine or at
      nonnicotinic receptors.

PMID- 15984654
TI  - The relationship between respiratory sinus arrhythmia and heart rate during
      anesthesia in rat.
AB  - During inspiration the heart rate (HR) increases and during expiration it
      decreases. Contribution of respiratory sinus arrhythmia (RSA) to spontaneous
      heart rate variability (HRV) can be measured as the high frequency (HF) component
      of variation in consecutive R-R intervals on ECG. In conscious rats, slowing of
      HR is associated with an increase in HF. The aim of this study was to investigate
      whether this relationship between HF and HR is preserved during anesthesia in
      rat. A 15 minutes long ECG signal was recorded from rats (N=15) under moderate
      chloral hydrate (CHL) anesthesia. Recordings were extended with 45 minutes to
      investigate the effect of atropine (N=3), against controls (N=3). Short term HRV
      was investigated in 30 seconds long epochs. HF was considered the frequency band
      between 0.8 and 1.6 Hz. RSA was quantified as the relative spectral power of the
      HF. Respiratory frequency (RF) was quantified as the mean spectral frequency
      within the HF band. One minute estimates of HR, RSA and HF were calculated by
      averaging 3 epochs of 30 seconds overlapped 50%. The average HR was 427 +/- 3
      bpm. The magnitude of RSA was 45 +/- 1% at a RF of 71 +/- 1 rpm. We found that:
      (1) the decrease in HR that occurs during CHL anesthesia in rat correlates with
      an increase in RSA; (2) atropine reduces RSA and the time-dependent decrease in
      HR; (3) the time-dependent increase in RSA is preserved after atropine. We
      conclude that the correlation between RSA and HR reflects the cardio-pulmonary
      coupling under parasympathetic control.

PMID- 15984655
TI  - Modification of the muscular contractility of the vena porta in trypsinemia.
AB  - The purpose of the present work was to investigate the changes of spontaneous and
      induced contractility in the rat vena porta, in conditions of acute pancreatitis,
      artificial trypsinemia and direct action of trypsin. The amplitude, frequency and
      mainly the intensity of the structure functioning decrease significantly under
      the influence of proteolitic enzymes (trypsin). The contractility of the isolated
      portal vein decrease in reply of the increase or decrease of the concentration of
      Ca2+ ions. Thus the possible action mechanism of proteolitic enzymes action
      consists in damaging at the sarcolemma, which causes the decrease in the influx
      of Ca2+ ions during the action potential.

PMID- 15984656
TI  - In vivo and in vitro research on the biological effects of deuterium-depleted
      water: 1. Influence of deuterium-depleted water on cultured cell growth.
AB  - Deuterium depleted-water (DDW) is a new available tool for decreasing deuterium
      concentration in the environment of cells in culture. Several types of
      established cell lines, both normal and neoplastic were grown in culture media
      dissolved with DDW and compared with the same strains, in the same amounts, grown
      in media dissolved with normal distilled water. Naive mice splenocytes were
      grown, under stimulation with proliferation triggers, like bacterial
      lipopolysaccharide (LPS) and Concanavalin A (ConA) in the same conditions. The
      growth and proliferation were estimated using the MTT assay. Both established
      cell types and explanted splenocytes in the DDW-media had a significantly higher
      growth rate than cell cultured in normal media. In an attempt to identify the
      membrane mechanisms involved in the growth stimulation by DDW, the membrane
      proton transporters Na+/H+ antiporter and H+/K+ATP-ase were inhibited with their
      selective blockers amiloride and respectively lansoprazole. The results, however
      incomplete, point towards a lack of involvement of the Na+/H+ antiporter and a
      possible implication of the H+/K+ATP-ase.

PMID- 15984657
TI  - Modelling of ion permeation in K+ channels by nonequilibrium molecular dynamics
      simulations: I. Permeation energetics and structure stability.
AB  - Because of the great importance of physiological and pathophysiological processes
      in which ion channels are involved and because their operation is described by
      physicochemical laws, there have been many attempts to develop physical models
      able to describe the membrane permeability and also the structural and functional
      properties of the channel protein structures. In this study (in two parts) we
      present a series of simulations on a K+ channel model (KcsA) using Nonequilibrium
      Molecular Dynamics simulations (NEMD), in order to follow structure stability,
      permeation energetics and the possibility of obtaining quantitative information
      about the permeation process using the Linear Response Theory (LRT). On K+ ions
      were applied external forces to determine them to pass through the channel in a
      relatively small amount of time, accessible computationally. We ascertained a
      high resistance of the protein to deformation even in conditions when great
      forces were applied on ions (the system was far from equilibrium). The estimation
      of energy profiles in the course of ions passage through the channel demonstrates
      that these proteins create a conductivity pathway with no energetic barriers for
      ions movement across the channel (which could be present due to ions
      dehydration). The dynamic model used demonstrates (as proposed before in the
      literature after the examination of the static KcsA structure obtained by X-Ray
      crystallography) that this is due to the interaction of ions with the negatively
      charged carbonyl oxygens of the main polypeptide chain in the selectivity filter
      region.

PMID- 15984658
TI  - New technical approaches in stereotaxic catheterization of cerebral ventriculi:
      implications for the L-arginine/NO synthase/nitric oxide cascade.
AB  - In order to study the actions of certain substances at cerebral level, a
      stereotactic device for ensuring a precise catheterization of points in certain
      cerebral areas was used. For the operation technique was used a stereotaxic atlas
      specifically designed for rat brain (G. Paxinos, C. Watson, 1998), which offers
      all the necessary information for the identification of the trepanation.
      Stereotaxic implantation of cannules in the brain is useful for microinjecting
      solutions containing various substances (in amounts of microl), directly and
      targeted in the anatomical structures of the brain. The technique described can
      use either metalic or silastic cannules, that have variable lumen (usually for
      adapting a Hamilton syringe). The cannules can be implanted at cerebroventricular
      level, having the possibility to target all the cerebral ventricles. The
      intracerebroventricular (icv) administration of L-arginine induces a significant
      increase of response latency for mechano-algesic test. The most obvious changes
      are induced following the administration of the association of L-NAME with L
      arginine, situation when is manifested an important increase of the response
      latency, starting with 5 minutes post-administration and continuing up to 45
      minutes determination. The increase is significantly higher compared with the
      results obtained with L-arginine alone. A similar evolution is registered in the
      case of the plantar test.

PMID- 15984660
TI  - Motor cortex plasticity--from physiology to clinical neurology.
AB  - Neurophysiologic, neuroanatomic and neuroimaging studies conducted over the past
      two decades reveal that the cerebral cortex is functionally and structurally
      dynamic. The functional topography of the motor cortex can be modified by a
      variety of experimental manipulations, including peripheral or central injury,
      electrical stimulation, pharmocologic treatment or behavioral experience. Recent
      evidence demonstrates that functional alterations in motor cortex organization
      are accompanied by changes in dendritic and synaptic structure, as well as
      alterations in the regulation of cortical neurotransmitter systems. This article
      describes the state of the science regarding the main mechanisms implicated in
      the motor cortex plasticity, the main tools used for its investigation and the
      consequence of the recent discoveries on the therapeutic and rehabilitation
      procedures for the brain-injured persons.

PMID- 15984659
TI  - Study of the cerebral vascular Doppler velocimetry and EEG in a group of 18 cases
      of Alzheimer's disease.
AB  - The authors studied the cerebral irrigation on a group of 18 patients with
      Alzheimer disease (60-70 year old) using the Doppler (D) ultrasound vascular
      method and EEG. They used a type UDP-10 Sonopan, with a sound acquisition system
      and graphic of recording on a 6 NEK-4 polyrecorder for registration of the
      carotid D curves together with ECG and phonocardiogram. EEG was registered using
      a Bioscript 2000. The statistical analysis of the D curves parameters for a group
      of 18 patients, compared to the parameters of a group of 40 clinically healthy
      persons, showed a decrease of the systolic speed with 24% and of the diastolic
      speed with 11%, a delay of the flow with the systolic spike in plateau and a
      murmur at the carotid arteries in 33% of the patients. These modifications point
      to the reduction of the cerebral vascular filling, determined especially by the
      atherosclerosis process which causes important narrowing of the vascular lumen
      but probably determined by Alzheimer disease also. We remarked the presence of
      theta waves in 42% of the patients and a small correlation (r = 0.38) with the
      decrease of the systolic speed in the test group.

PMID- 15984661
TI  - Pathogenic pathways in acute myeloid leukemias.
AB  - Despite the common clinical, hematological and prognostic features that define
      acute myeloid leukemia (AML) there is considerable heterogeneity among individual
      cases, suggesting different pathogenic pathways. Based on a simple theoretical
      model, according to the vital characteristics of the leukemic clone
      (proliferative rate and resistance to apoptosis) we propose a classification of
      AML into two broad categories: a) high leukemic clone vitality (HLV) AML,
      corresponding roughly to the World Health Organization (WHO) classification group
      of entities "AML with recurrent cytogenetic abnormalities" and b) low leukemic
      clone vitality (LLV) or "opportunistic" AML corresponding to the WHO groups "AML
      with multilineage dysplasia" and "therapy-related AML". HLV-AML leukemic clones
      are characterized by rate-limiting genomic mutations capable of conferring
      proliferation/survival advantage over a normal hematopoietic environment while in
      LLV-AML, the leukemic clones are not particularly proliferative or apoptosis
      resistant, but are nevertheless selected against an impaired, previously damaged
      hematopoietic environment. Such a pathogenesis-oriented classification might have
      therapeutic and prognostic implications, providing a theoretical basis for a
      further adaptation of the current standard treatment strategies to the individual
      characteristics of the AML patients.

PMID- 15984662
TI  - Experimental data regarding the implications of certain minimum structure
      enkephalin-like peptides in nociceptive processing.
AB  - The aim of this study was to investigate the importance of the amino acidic
      sequence at N-terminal end of certain minimum structure enkephalin-like peptides
      for the analgesic activity. Different groups of mice or rats were treated with 1)
      L-tyrosine (i.p. 200 mg/kg), 2) Tyr-Phe (i.t. 0.5 mg/rat), 3) Tyr-Pro-Phe (i.t.
      0.5 mg/rat), 4) Gly-Tyr (i.t. 0.5 mg/rat), 5) Tyr-Gly-Gly (i.t. 0.5 mg/rat).
      Different tests were utilized to evaluate the antinociceptive effect of the
      substances tested: thermal nociception (hot plate test, plantar test), mechanical
      nociception (analgesymeter test). Tyr-Pro-Phe, Tyr-Gly-Gly, Tyr-Phe, but not Gly
      Tyr, elicited analgesic activity. So, the presumption made in the case of
      atypical opioid peptides that opioid-like activity in case of peptides presumes a
      tyrosine residue at the N-terminal sequence, applies for shorter peptides. It
      appears also that minimal structure brain peptides with an N-terminal Tyr-Pro,
      rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous opioids, can
      provide better affinity for the opioid receptors and stronger analgesic activity.
      The inhibition of their analgesic effect by previous administration of naloxone
      proves that this effect is mediated through the endogenous opioid system.

PMID- 15984663
TI  - The sympatho-adrenal response and erythropoietin production in adaptation to
      hypoxia.
AB  - The research activity upon erythropoiesis regulation carried out by the team in
      the Physiology Department and in the Institute of Medical Research of the
      Romanian Academy in Cluj-Napoca developed continuously after 1950. Our studies
      contributed to the isolation, identification and characterization of
      erythropoietin (Epo) and also to a better understanding of the nervous adaptation
      mechanisms to hypoxia. At present, it is well known that hypoxia acts upon
      erythropoiesis through Epo production. Direct central nervous stimulation through
      hypoxia induces, via a neuro-humoral mechanism, a sympatho-adrenal response and
      release of Epo. Adaptive polyglobulia as a response to hypoxia increases the
      capacity of oxygen binding and transport. In this paper we attempted to identify
      the role of the sympathetic nervous system in adaptation to hypoxia correlated
      with Epo secretion. Experiments were carried out in three groups of rats,
      respectively, with cervical, thoracic, and lumbar (without celiac) sympathectomy.
      The sympathectomized animals were submitted to hypobaric or to hemorrhagic
      hypoxia, in parallel with control groups. Erythrocytic parameters (red blood
      cells, reticulocytes, hematocrit, and haemoglobin) were repeatedly assayed during
      the following 2-4 weeks. The results showed that animals with cervical
      sympathectomy adapt in a deficient manner to hypoxia; lacking the adaptive sino
      carotid reflexes, adaptation occurs through increased Epo secretion, animals with
      cervical sympathectomy having higher counts of reticulocytes and of red blood
      cells at the end of experiment than intact animals. Thoracic sympathectomy has
      little influence upon the erythrocytic response, as the largest part of the
      respiratory and circulatory sympathetic reactions occur via the cervical
      sympathetic nerve. Lumbar sympathectomy without removal of the celiac ganglion
      does not decrease the erythrocytic response as expected; on the contrary, the
      erythrocytic response is increased as compared to controls.

PMID- 15984664
TI  - Circadian phagocytic activity in rats under light-dark and constant light
      regimens.
AB  - The phagocytic function was proved to be a periodic, circadian process. Its
      acrophase appears to be differently timed in species with different activity
      type, occurring in the evening in diurnal species and at night in nocturnal ones.
      The main pineal hormone melatonin, whose secretion occurs strictly at dark, has
      been shown to play a role in the control of inflammation and to exert a certain
      stimulatory effect upon phagocytosis in vitro. The aim of the present study was
      to assess whether the phagocytic activity of neutrophils in the blood of rats
      exhibits a circadian rhythmicity similar to that of other nocturnal rodents
      (mice) and also if a constant light regimen alters its amplitude and/or
      chronostructure. Wistar rats were submitted to either an artificial light-dark
      12/12 regimen (LD) or to constant light (LL), for 15 days. In vitro phagocytosis
      of the neutrophils in whole blood against E.coli was assessed at 10:00, 16:00,
      22:00, and 04:00 hours. In LD, phagocytosis appears to be a rhythmical function,
      with statistically significant differences between the highest value at 04:00 hrs
      and the lowest at 10:00 hrs. Constant light induces a 30% depression of the
      phagocytic ability throughout the whole 24 hours cycle, without altering its
      oscillations. The darkness period appears to play the role of a synchronizer; in
      its absence the rhythm tends to free-run. It may be stated that rhythmical
      melatonin secretion is responsible only for maintenance of the phagocytic level,
      probably via the anterior hypothalamic area and thymus, while it cannot account
      directly for the nocturnal increase of phagocytosis.

PMID- 15984665
TI  - Neutrophil adherence in rats submitted to light-dark alternance and to constant
      light.
AB  - A good amount of experimental data suggests the existence of a circadian control
      of the inflammatory process. It was shown that migration of neutrophils in
      chemotactic gradient, ingestion of particles, vascular permeability etc. are
      rhythmical circadian functions. Melatonin, the pineal hormone secreted during the
      darkness phase, has been shown to be involved in the control of inflammation. The
      present study aims to assess whether neutrophil adherence to nylon fibers
      exhibits circadian rhythmicity and also if its amplitude and/or chronostructure
      are altered in a constant light regimen. Wistar rats were submitted to either an
      artificial light-darkness 12/12 regimen (LD) or to constant light (LL), for 15
      days. Adherence of the neutrophils in whole blood was assessed at 10:00, 16:00,
      22:00, and 04:00 hrs. In LD. neutrophil adherence appears to be a rhythmic,
      biphasic function, with the acrophase at 10:00, a secondary peak at 22:00 and
      trough values in the late dark hours. Constant light induces a depression of the
      adherence ability by about 10%, except for the 04:00 hrs point, where the value
      in LL is higher than in LD. The fact that adherence and phagocytic activity do
      not oscillate in phase suggests that the physiological relevance of neutrophil
      adherence goes beyond that of a first stage of the phagocytic process.

PMID- 15984666
TI  - A metaanalysis of certain erythropoietin characteristics established before
      recombinant EPO was obtained.
AB  - Beginning with 1975, our group has performed some studies using an erythropoietin
      (EPO ) extract prepared according to an original technique from sera of anemic
      rabbits. Our results have contributed to the understanding of the glycoproteinic
      nature of this extract as well as of some of its biological features. These
      results were confirmed only after 1985, when recombinant EPO was obtained. The
      aim of this study is to emphasize some of our priorities, controversial at that
      time. We have shown the radioprotective effect of an EPO extract, in correlation
      with red cell proliferation and with an increased rate of nucleic acid metabolism
      and bone marrow blood flow. Consequently, we proposed the investigation of the
      bone marrow function using EPO. Our results are correlated with recent data
      obtained with recombinant EPO. They refer to the ability of EPO to prevent
      apoptosis, its antioxidant effects, and its ability to modulate the
      sympathoadrenal response to hypoxia.

PMID- 15984667
TI  - Cerebral excitability and the mechanisms of blood transportation of sodium.
AB  - The basic, fundamental property of living structures is excitability. This
      process defines how an organism responds to both internal and external stimuli.
      Previous studies have indicated the existence of physical and chemical
      interactions between cations and anions sites of proteins within the
      extracellular environment that have a specific functional importance. However, it
      is not well understood whether specific cations may alter the function of
      specific proteins. We report here the results of studies that indicate
      interaction of specific cations such as sodium may alter the physico-chemical
      action of heparin. The importance of these interactions is discussed.

PMID- 15984668
TI  - Forecasting of top athletic performance.
AB  - The limiting factors of top athletic performance and the psycho-physiological
      mechanisms involved remain controversial. The aim of this study was to attempt a
      prediction of world records (WR) for the next ten years in five athletic track
      and field and events. Our prediction has been produced by means of computer-
      aided mathematical models. In short, polynomials that could best approximate the
      WR of the last decades have been calculated and projected over the period 2000
      2010. The predicted values for the year 2010 point to an improvement rate of the
      WR considered varying between 0.2% and 10.3%, depending on event and gender.
      Those values could be influenced by the use of better sports equipment, better
      nutrition and training and especially by the impact of doping and of anti-doping
      measures.

PMID- 15984669
TI  - Clinical engineering in Romania. The coming of age.
AB  - Biomedical engineering (BME) includes clinical engineering and bioengineering.
      Bioengineering is academically oriented towards theory and research in biology
      using the methods of exact sciences such as maths and physics, while clinical
      engineering (CE) has a rather practical orientation focusing on the general
      management of clinic/hospital equipment and providing aid to the medical staff in
      the use of advanced technologies for diagnosis and therapy purposes. The Romanian
      physiological community has been closely involved in the growth of BME that has
      now come of age in this country. Radu Vrancianu's great intuition in opening the
      door to this science and its practical application in an institution created by
      Daniel Danielopolu definitely represented a good chance for Romanian public
      health. Recently, both clinical engineering and medical bioengineering have been
      introduced into the Romanian Classification of Occupations.

PMID- 15984670
TI  - Control and variability of gene expression in mouse brain and in a neuroblastoma
      cell line.
AB  - We used cDNA microarrays to examine the extent to which the expression of
      individual genes varies in mouse brain and in cultured N2A neuroblastoma cells
      mRNA extracted from sixC57B1/6J neonatal mouse brains and from four distinct
      cultures of N2A neuroblastoma cells was cross-hybridized with ten AECOM cDNA
      microarray chips to determine the individual gene expression variability. A
      mathematical algorithm reduced the effect of potential sources of variability not
      associated to the biological material by about 80%. The interval estimates of the
      standard deviation of individual gene expressionwere determined through chi
      square statistics. The newly introduced relative expression variability, defined
      as the quotient of the middle of the interval estimate of the standard deviation
      and the mean expression ratio (and its inverse, gene transcription control), was
      used to rank the most unstably and the most stably transcribed genes. In brains
      of different animals and in separate cultures of N2A cells, unique sets ofgenes
      exhibited exceptional stability or were highly variable. Possible implications
      for such tight or loose transcriptional control are discussed.

PMID- 15984671
TI  - Transcriptomic characterization of four classes of cell-cell/cell-matrix genes in
      brains and hearts of wild type and connexin43 null mice.
AB  - We have used a highly quantifiable cDNA microarray method to determine the
      stabilities and expression levels within gene families involved in cell-cell and
      cell-matrix interactions in neonatal mouse brain and heart. In addition, we have
      characterized the extent to which deletion of the gap junction protein connexin43
      (Cx43) affects these characteristics. Our observations for individual genes
      revealed a range of differences and variabilities in transcription level among
      family members; calculation of the genomic patholog (a global measure of gene
      expression alteration) indicates that these cell interaction genes contribute
      disproportionately to the overall phenotype. We found significant transcriptomic
      differences between brain and heart, that deletion of Cx43 considerably decreased
      gene expression variability and that the average contribution to the pathology of
      the genes whose encoded proteins are involved in cell-cell or cell-matrix
      interaction in the Cx43-null mice was about twenty times higher than that of
      other genes. These findings indicate that gap junction gene expression influences
      the expression of other genes involved in intercellular and cell-substrate
      interaction and that expression of these genes is under strong regulatory
      pressure in the Cx43-null mouse, presumably representing a compensatory response
      to Cx43 deletion.

PMID- 15984672
TI  - The development of technologies for molecular imaging should be driven
      principally by biological questions to be addressed rather than by simply
      modifying existing imaging technologies. For the proposition.

PMID- 15984673
TI  - The development of technologies for molecular imaging should be driven
      principally by biological questions to be addressed rather than by simply
      modifying existing imaging technologies. Against the proposition.

PMID- 15984674
TI  - Improving IMRT delivery efficiency using intensity limits during inverse
      planning.
AB  - Inverse planned intensity modulated radiotherapy (IMRT) fields can be highly
      modulated due to the large number of degrees of freedom involved in the inverse
      planning process. Additional modulation typically results in a more optimal plan,
      although the clinical rewards may be small or offset by additional delivery
      complexity and/or increased dose from transmission and leakage. Increasing
      modulation decreases delivery efficiency, and may lead to plans that are more
      sensitive to geometrical uncertainties. The purpose of this work is to assess the
      use of maximum intensity limits in inverse IMRT planning as a simple way to
      increase delivery efficiency without significantly affecting plan quality. Nine
      clinical cases (three each for brain, prostate, and head/neck) were used to
      evaluate advantages and disadvantages of limiting maximum intensity to increase
      delivery efficiency. IMRT plans were generated using in-house protocol-based
      constraints and objectives for the brain and head/neck, and RTOG 9406 dose volume
      objectives in the prostate. Each case was optimized at a series of maximum
      intensity ratios (the product of the maximum intensity and the number of beams
      divided by the prescribed dose to the target volume), and evaluated in terms of
      clinical metrics, dose-volume histograms, monitor units (MU) required per
      fraction (SMLC and DMLC delivery), and intensity map variation (a measure of the
      beam modulation). In each site tested, it was possible to reduce total monitor
      units by constraining the maximum allowed intensity without compromising the
      clinical acceptability of the plan. Monitor unit reductions up to 38% were
      observed for SMLC delivery, while reductions up to 29% were achieved for DMLC
      delivery. In general, complicated geometries saw a smaller reduction in monitor
      units for both delivery types, although DMLC delivery required significantly more
      monitor units in all cases. Constraining the maximum intensity in an inverse IMRT
      plan is a simple way to improve delivery efficiency without compromising plan
      objectives.

PMID- 15984675
TI  - Radiological properties of a wax-gypsum compensator material.
AB  - In this paper the radiological properties of a compensator material consisting of
      wax and gypsum is presented. Effective attenuation coefficients (EACs) have been
      determined from transmission measurements with an ion chamber in a Perspex
      phantom. Measurements were made at 80 and 100 cm source-to-skin distance (SSD)
      for beam energies of 6, 8, and 15 MV, for field sizes ranging from narrow beam
      geometries up to 40 x 40 cm2, and at measurement depths of maximum dose build-up,
      5 and 10 cm. A parametrization equation could be constructed to predict the EAC
      values within 4% uncertainty as a function of field size and depth of
      measurement. The EAC dependence on off-axis position was also quantified at each
      beam energy and SSD. It was found that the compensator material reduced the
      required thickness for compensation by 26% at 8 MV when compared to pure paraffin
      wax for a 10 x 10 cm2 field. Relative surface ionization (RSI) measurements have
      been made to quantify the effect of scattered electrons from the wax-gypsum
      compensator. Results indicated that for 80 cm SSD the RSI would exceed 50% for
      fields larger than 15 x 15 cm2. At 100 cm SSD the RSI values were below 50% for
      all field sizes used.

PMID- 15984676
TI  - Analytical representation for varian EDW factors at off-center points.
AB  - The purpose of this study is to describe and evaluate a new analytical model for
      Varian enhanced dynamic wedge factors at off-center points. The new model was
      verified by comparing measured and calculated wedge factors for the standard set
      of wedge angles (i.e., 15 degrees, 30 degrees, 45 degrees and 60 degrees),
      different symmetric and asymmetric fields, and two different photon energies. The
      maximum difference between calculated and measured wedge factors is less than 2%.
      The average absolute difference is within 1%. The obtained results indicate that
      the suggested model can be useful for independent dose calculation with enhanced
      dynamic wedges.

PMID- 15984677
TI  - Optimized source selection for intracavitary low dose rate brachytherapy.
AB  - A procedure has been developed for automating optimal selection of sources from
      an available inventory for the low dose rate brachytherapy, as a replacement for
      the conventional trial-and-error approach. The method of optimized constrained
      ratios was applied for clinical source selection for intracavitary Cs-137
      implants using Varian BRACHYVISION software as initial interface. However, this
      method can be easily extended to another system with isodose scaling and shaping
      capabilities. Our procedure provides optimal source selection results independent
      of the user experience and in a short amount of time. This method also generates
      statistics on frequently requested ideal source strengths aiding in ordering of
      clinically relevant sources.

PMID- 15984678
TI  - Monte Carlo calculations of the absorbed dose and energy dependence of plastic
      scintillators.
AB  - Detector systems using plastic scintillators can provide instantaneous
      measurements with high spatial resolution in many applications including small
      field and high dose gradient field applications. Energy independence and water
      equivalence are important dosimetric properties that determine whether a detector
      will be useful in a clinical setting. Using Monte Carlo simulations, we
      calculated the energy dependence of plastic scintillators when exposed to photon
      beams in the radiotherapeutic range. These calculations were performed for a
      detector comprised of a BC-400 plastic scintillator surrounded by a polystyrene
      wall. Our results showed the plastic scintillation detector to be nearly energy
      independent over a range of energies from 0.5 to 20 MeV. The ratio of the dose
      absorbed by the scintillator to that absorbed by water was nearly a constant,
      approximately equal to 0.98 over the entire energy range of interest. These
      results confirm the water equivalence of the plastic scintillation detector and
      are in very good agreement with earlier results obtained using Burlin cavity
      theory.

PMID- 15984679
TI  - Focal beam distortion and treatment planning in abdominal focused ultrasound
      surgery.
AB  - Recent clinical trials show promising results in using MRI and MRI-based
      thermometry to guide focused ultrasound surgery to treat uterine fibroids. During
      treatment, large variation in the focal temperature distribution has been
      observed. It is possible that some of this variation is due to abdominal tissue
      inhomogeneity, which might be causing focal beam distortion, and might largely
      decrease the focusing ability in deep-seated tissues. The purpose of this study
      was to numerically demonstrate this effect and also show the feasibility of
      restoring the focal beam patterns by employing the phase correction procedure for
      phased arrays. Abdominal MR data from four uterine fibroid patients were obtained
      to reconstruct the three-dimensional meshes of interfaces used in simulations,
      and one patient was selected to perform the analysis of key parameters in focused
      ultrasound surgery. Results show that, without phase correction, the focused beam
      can be severely distorted while using a frequency above 1 MHz or delivering ring
      shape focal patterns. Different focal positions at the same depth may require a
      different power to induce the same ultrasonic intensity level (up to 179% among
      the different focal patterns). After adding a phase correction procedure, the
      distorted focal beams can be restored, and the peak intensity can be largely
      recovered (up to 85% among the different focal patterns). This study may offer
      important implications and information for treatment planning toward optimizing
      focused ultrasound surgery in uterine fibroid or other abdominal tumor
      treatments.

PMID- 15984680
TI  - Characterization of electron contamination in megavoltage photon beams.
AB  - The purpose of the present study is to characterize electron contamination in
      photon beams in different clinical situations. Variations with field size, beam
      modifier (tray, shaping block) and source-surface distance (SSD) were studied.
      Percentage depth dose measurements with and without a purging magnet and
      replacing the air by helium were performed to identify the two electron sources
      that are clearly differentiated: air and treatment head. Previous analytical
      methods were used to fit the measured data, exploring the validity of these
      models. Electrons generated in the treatment head are more energetic and more
      important for larger field sizes, shorter SSD, and greater depths. This
      difference is much more noticeable for the 18 MV beam than for the 6 MV beam. If
      a tray is used as beam modifier, electron contamination increases, but the energy
      of these electrons is similar to that of electrons coming from the treatment
      head. Electron contamination could be fitted to a modified exponential curve. For
      machine modeling in a treatment planning system, setting SSD at 90 cm for input
      data could reduce errors for most isocentric treatments, because they will be
      delivered for SSD ranging from 80 to 100 cm. For very small field sizes, air
      generated electrons must be considered independently, because of their different
      energetic spectrum and dosimetric influence.

PMID- 15984681
TI  - Time delay measurement for linac based treatment delivery in synchronized
      respiratory gating radiotherapy.
AB  - A time delay in a respiratory gating system could cause an unexpected phase
      mismatch for synchronized gating radiotherapy. This study presents a method of
      identifying and measuring the time delay in a gating system. Various port films
      were taken for a motion phantom at different gating window levels with a very
      narrow window size. The time delay for the gating system was determined by
      comparing the motion curve (the position of a moving object versus the gating
      time) measured in the port films to the motion curve determined by the video
      cameras. The measured time delay for a linac-based gating system was 0.17+/-0.03
      s. This time delay could induce target missing if it was not properly taken into
      account for the synchronized gating radiotherapy. Measurement/verification of the
      time delay should be considered as an important part of the
      accepting/commissioning test before the clinical use of the gating system.

PMID- 15984682
TI  - Noninvasive reflection spectra provide quantitative information about the spatial
      distribution of skin chromophores.
AB  - In this work, a new method of analyzing noninvasive reflection spectra is
      presented. The approach explicitly models the inhomogeneity of chromophore
      distributions in living tissues and thus extracts not only apparent chromophore
      concentrations but also relative chromophore distributions in tissues.
      Furthermore, it works with spectra obtained with short source-detector
      separations where the diffusion theory of light transport through turbid media is
      not valid, and formerly presented methods thus fail. The effect of
      inhomogeneously distributed chromophores in a multicompartment model of tissues
      on measured reflection spectra is explained and an algorithm to deconvolute
      tissue spectra based on this model is presented. It is evaluated using simulated
      spectra and measurements on phantoms, which are made up of partially printed
      pieces of paper to simulate inhomogeneous dye distributions. Its applicability to
      real tissue is proven using reflection spectra obtained with 130 microm source
      detector separation from a hemoperfusion stop experiment. The proposed model
      accurately determines apparent chromophore concentrations and corresponding
      distributions in simulated spectra and phantoms. Regarding real tissue spectra,
      the results correspond to former publications and the spectral reconstruction
      yields only minimal residuals, indicating a complete and accurate spectral
      deconvolution. In conclusion, the presented approach is a suitable extension and
      amendment to existing models of light transport through inhomogeneous samples.

PMID- 15984683
TI  - Modality independent elastography (MIE): potential applications in dermoscopy.
AB  - The use of palpation information for skin disease characterization is not as
      commonly used as in other soft tissues, although mechanical differences within
      lesions have been noted. For example, regions of hyperkeratosis have the
      potential to transform into cancerous lesions and likely feature different
      material properties from those of surrounding normal tissue due to varying
      cytoarchitecture. As a result, the spatial distribution of lesion mechanical
      properties may serve to assist a diagnosis or enhance visualization of the
      complete extent of a cancerous region, i.e., accurate information regarding the
      margins of disease for surgical therapy. In this work, a multiresolution
      extension to a novel elastographic imaging method called Modality Independent
      Elastography (MIE) is used to characterize the mechanical properties of a skin
      like phantom embedded with a mock stiff lesion. Simulation studies were also
      performed to investigate the potential for characterizing realistic melanoma
      lesions. Elasticity image reconstructions from the phantom experiments localized
      the stiff inclusion and had good correlation between the Young's modulus contrast
      ratio and experimental measurements from material testing. In addition,
      multiresolution MIE was shown to be a more robust framework than its single
      resolution version. Results from the melanoma simulation demonstrate the
      potential for using multiresolution MIE with dermoscopic images.

PMID- 15984684
TI  - Presampling, algorithm factors, and noise: considerations for CT in particular
      and for medical imaging in general.
AB  - CT scanners acquire noisy data at discrete sample positions. Typically, a
      convention of how to continue these data from discrete integer positions to the
      continuous domain must be applied during processing. We study the properties of
      three typical one-dimensional spatial domain interpolation algorithms in terms of
      a cost or quality factor Q. This figure of merit Q is a function of spatial
      resolution, data noise, and dose and is used to optimize detector design. Spatial
      resolution R is defined as either mean square width delta or as the full width at
      half maximum W of the point spread function (PSF). Our results show that a
      trapezoidal interpolation algorithm is optimal for the high resolution domain
      (relative to the detector aperture size g) and should be replaced by a triangular
      or Gaussian interpolation function for spatial resolutions of about 1.3g or
      larger; these result in bell-shaped PSFs. Assuming such a hybrid algorithm we
      find a 1.5-fold increase of Q2-this is equivalent to 50% improved dose usage-when
      smoothing the data to a spatial resolution of 3g or more compared to a highest
      resolution reconstruction. Therefore it is advisable to use detectors of one
      third of the size of the desired spatial resolution W and to compensate for the
      1.5-fold increase in Q2 by reducing dose by 33%. Under the presence of moderately
      sized septa (e.g., 10% of the spatial resolution element size) the benefit of
      optimizing still lies in the order of 30% improved dose usage; in that case the
      detector size g should be on the order of W/2 and a dose reduction of 23% can be
      achieved. Again, bell-shaped PSFs show a better tradeoff between noise and
      resolution for a given dose than rectangular-shaped PSFs. The general
      interpretation of our results is that the degree of freedom of choosing the
      weighting or interpolation function for a given resolution is large for small
      detectors and small for large detectors. Thus systems with small g have a higher
      potential of optimization compared to systems with large g. Similarly, detector
      binning, which corresponds to replacing g by 2g, should be avoided. Note that the
      figures reported correspond to a one-dimensional interpolation. Two-dimensional
      detectors typically separate and resulting quality factors can be easily obtained
      by multiplication. Then, Q2 is expected to improve by a factor of 1.52 without
      septa and by a factor of 1.32 with septa. This indicates that dose can be reduced
      by about 56% and about 41%, respectively. Our findings are general and not
      restricted to CT. They can be readily applied to medical or nonmedical imaging
      devices and digital detectors and they may also turn out to be useful in other
      fields.

PMID- 15984686
TI  - A Monte Carlo derived TG-51 equivalent calibration for helical tomotherapy.
AB  - Helical tomotherapy (HT) requires a method of accurately determining the absorbed
      dose under reference conditions. In the AAPM's TG-51 external beam dosimetry
      protocol, the quality conversion factor, kQ, is presented as a function of the
      photon component of the percentage depth-dose at 10 cm depth, %dd(10)x, measured
      under the reference conditions of a 10 x 10 cm2 field size and a source-to
      surface distance (SSD) of 100 cm. The value of %dd(10)x from HT cannot be used
      for the determination of kQ because the design of the HT does not meet the
      following TG-51 reference conditions: (i) the field size and the practical SSD
      required by TG-51 are not obtainable and (ii) the absence of the flattening
      filter changes the beam quality thus affecting some components of kQ. The
      stopping power ratio is not affected because of its direct relationship to
      %dd(10)x. We derive a relationship for the Exradin A1SL ion chamber converting
      the %dd(10)x measured under HT "reference conditions" of SSD=85 cm and a 5 x 10
      cm2 field-size [%dd(10)x[HT Ref]], to the dosimetric equivalent value under for
      TG-51 reference conditions [%dd(10)x[HT TG-51]] for HT. This allows the
      determination of kQ under the HT reference conditions. The conversion results in
      changes of 0.1% in the value of kQ for our particular unit. The conversion
      relationship should also apply to other ion chambers with possible errors on the
      order of 0.1%.

PMID- 15984685
TI  - A method and software for segmentation of anatomic object ensembles by deformable
      m-reps.
AB  - Deformable shape models (DSMs) comprise a general approach that shows great
      promise for automatic image segmentation. Published studies by others and our own
      research results strongly suggest that segmentation of a normal or near-normal
      object from 3D medical images will be most successful when the DSM approach uses
      (1) knowledge of the geometry of not only the target anatomic object but also the
      ensemble of objects providing context for the target object and (2) knowledge of
      the image intensities to be expected relative to the geometry of the target and
      contextual objects. The segmentation will be most efficient when the deformation
      operates at multiple object-related scales and uses deformations that include not
      just local translations but the biologically important transformations of bending
      and twisting, i.e., local rotation, and local magnification. In computer vision
      an important class of DSM methods uses explicit geometric models in a Bayesian
      statistical framework to provide a priori information used in posterior
      optimization to match the DSM against a target image. In this approach a DSM of
      the object to be segmented is placed in the target image data and undergoes a
      series of rigid and nonrigid transformations that deform the model to closely
      match the target object. The deformation process is driven by optimizing an
      objective function that has terms for the geometric typicality and model-to-image
      match for each instance of the deformed model. The success of this approach
      depends strongly on the object representation, i.e., the structural details and
      parameter set for the DSM, which in turn determines the analytic form of the
      objective function. This paper describes a form of DSM called m-reps that has or
      allows these properties, and a method of segmentation consisting of large to
      small scale posterior optimization of m-reps. Segmentation by deformable m-reps,
      together with the appropriate data representations, visualizations, and user
      interface, has been implemented in software that accomplishes 3D segmentations in
      a few minutes. Software for building and training models has also been developed.
      The methods underlying this software and its abilities are the subject of this
      paper.

PMID- 15984687
TI  - Accounting for beta-particle energy loss to cortical bone via paired-image
      radiation transport (PIRT).
AB  - Current methods of skeletal dose assessment in both medical physics (radionuclide
      therapy) and health physics (dose reconstruction and risk assessment) rely
      heavily on a single set of bone and marrow cavity chord-length distributions in
      which particle energy deposition is tracked within an infinite extent of
      trabecular spongiosa, with no allowance for particle escape to cortical bone. In
      the present study, we introduce a paired-image radiation transport (PIRT) model
      which provides a more realistic three-dimensional (3D) geometry for particle
      transport in the skeletal site at both microscopic and macroscopic levels of its
      histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and
      individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For
      the three skeletal sites, regions of trabecular spongiosa and cortical bone were
      identified and segmented. Physical sections of interior spongiosa were taken and
      subjected to microCT imaging. Voxels within the resulting microCT images were
      then segmented and labeled as regions of bone trabeculae, endosteum, active
      marrow, and inactive marrow through application of image processing algorithms.
      The PIRT methodology was then implemented within the EGSNRC radiation transport
      code whereby electrons of various initial energies are simultaneously tracked
      within both the ex vivo CT macroimage and the CT microimage of the skeletal site.
      At initial electron energies greater than 50-200 keV, a divergence in absorbed
      fractions to active marrow are noted between PIRT model simulations and those
      estimated under existing techniques of infinite spongiosa transport. Calculations
      of radionuclide S values under both methodologies imply that current chord-based
      models may overestimate the absorbed dose to active bone marrow in these skeletal
      sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by
      approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and
      89Sr), and by approximately 14% to 76% for high-energy beta emitters (32p, 188Re,
      and 90Y). The PIRT methodology allows for detailed modeling of the 3D
      macrostructure of individual marrow-containing bones within the skeleton thus
      permitting improved estimates of absorbed fractions and radionuclide S values for
      intermediate-to-high energy beta emitters.

PMID- 15984688
TI  - A conversion method of air kerma from the primary, scatter, and leakage
      radiations to effective dose for calculating x-ray shielding barriers in
      mammography.
AB  - In this study, a new approach has been introduced for derivation of the effective
      dose from air kerma to calculate shielding requirements in mammography
      facilities. This new approach has been used to compute the conversion
      coefficients relating air kerma to the effective dose for the mammography
      reference beam series of the Netherlands Metrology Institute Van Swinden
      Laboratorium, National Institute of Standards and Technology, and International
      Atomic Energy Agency laboratories. The results show that, in all cases, the
      effective dose in mammography energy range is less than 25% of the incident air
      kerma for the primary and the scatter radiations and does not exceed 75% for the
      leakage radiation.

PMID- 15984689
TI  - Development of ultrasound tomography for breast imaging: technical assessment.
AB  - Ultrasound imaging is widely used in medicine because of its benign
      characteristics and real-time capabilities. Physics theory suggests that the
      application of tomographic techniques may allow ultrasound imaging to reach its
      full potential as a diagnostic tool allowing it to compete with other tomographic
      modalities such as x-ray computer tomography, and MRI. This paper describes the
      construction and use of a prototype tomographic scanner and reports on the
      feasibility of implementing tomographic theory in practice and the potential of
      ultrasound (US) tomography in diagnostic imaging. Data were collected with the
      prototype by scanning two types of phantoms and a cadaveric breast. A specialized
      suite of algorithms was developed and utilized to construct images of
      reflectivity and sound speed from the phantom data. The basic results can be
      summarized as follows. (i) A fast, clinically relevant US tomography scanner can
      be built using existing technology. (ii) The spatial resolution, deduced from
      images of reflectivity, is 0.4 mm. The demonstrated 10 cm depth-of-field is
      superior to that of conventional ultrasound and the image contrast is improved
      through the reduction of speckle noise and overall lowering of the noise floor.
      (iii) Images of acoustic properties such as sound speed suggest that it is
      possible to measure variations in the sound speed of 5 m/s. An apparent
      correlation with x-ray attenuation suggests that the sound speed can be used to
      discriminate between various types of soft tissue. (iv) Ultrasound tomography has
      the potential to improve diagnostic imaging in relation to breast cancer
      detection.

PMID- 15984690
TI  - Dose sculpting with generalized equivalent uniform dose.
AB  - With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose
      distribution can be produced using inverse planning. The generalized equivalent
      uniform dose (gEUD) has been used in IMRT optimization as an alternative
      objective function to the conventional dose-volume-based criteria. The purpose of
      this study was to investigate the effectiveness of gEUD optimization to fine tune
      the dose distributions of IMRT plans. We analyzed the effect of gEUD-based
      optimization parameters on plan quality. The objective was to determine whether
      dose distribution to selected structures could be improved using gEUD
      optimization without adversely altering the doses delivered to other structures,
      as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD0
      and n) based on the current dose distributions, the optimization system could be
      instructed to search for alternative solutions in the neighborhood, and we could
      maintain the dose distributions for structures already satisfactory and improve
      dose for structures that need enhancement. We started with an already acceptable
      IMRT plan optimized with any objective function. The dose distribution was
      analyzed first. For structures that dose should not be changed, a higher value of
      n was used and EUD0 was set slightly higher/lower than the EUD value at the
      current dose distribution for critical structures/targets. For structures that
      needed improvement in dose, a higher to medium value of n was used, and EUD0 was
      set to the EUD value or slightly lower/higher for the critical structure/target
      at the current dose distribution. We evaluated this method in one clinical case
      each of head and neck, lung and prostate cancer. Dose volume histograms, isodose
      distributions, and relevant tolerance doses for critical structures were used for
      the assessment. We found that by adjusting gEUD optimization parameters, the dose
      distribution could be improved with only a few iterations. A larger value of n
      could lead to faster convergence and a medium value of n could result in a search
      in a broader area. Such improvement could also be achieved by optimization based
      on other criteria, but the gEUD-based method has the advantage of efficiency and
      flexibility. Therefore, gEUD-based optimization can be used as a tool to improve
      IMRT plans by adjusting the planning parameters, thereby making dose sculpting
      feasible.

PMID- 15984691
TI  - Generalized DQE analysis of radiographic and dual-energy imaging using flat-panel
      detectors.
AB  - Analysis of detective quantum efficiency (DQE) is an important component of the
      investigation of imaging performance for flat-panel detectors (FPDs).
      Conventional descriptions of DQE are limited, however, in that they take no
      account of anatomical noise (i.e., image fluctuations caused by overlying
      anatomy), even though such noise can be the most significant limitation to
      detectability, often outweighing quantum or electronic noise. We incorporate
      anatomical noise in experimental and theoretical descriptions of the "generalized
      DQE" by including a spatial-frequency-dependent noise-power term, S(B),
      corresponding to background anatomical fluctuations. Cascaded systems analysis
      (CSA) of the generalized DQE reveals tradeoffs between anatomical noise and the
      factors that govern quantum noise. We extend such analysis to dual-energy (DE)
      imaging, in which the overlying anatomical structure is selectively removed in
      image reconstructions by combining projections acquired at low and high kVp. The
      effectiveness of DE imaging in removing anatomical noise is quantified by
      measurement of S(B) in an anthropomorphic phantom. Combining the generalized DQE
      with an idealized task function to yield the detectability index, we show that
      anatomical noise dramatically influences task-based performance, system design,
      and optimization. For the case of radiography, the analysis resolves a
      fundamental and illustrative quandary: The effect of kVp on imaging performance,
      which is poorly described by conventional DQE analysis but is clarified by
      consideration of the generalized DQE. For the case of DE imaging, extension of a
      generalized CSA methodology reveals a potentially powerful guide to system
      optimization through the optimal selection of the tissue cancellation parameter.
      Generalized task-based analysis for DE imaging shows an improvement in the
      detectability index by more than a factor of 2 compared to conventional
      radiography for idealized detection tasks.

PMID- 15984692
TI  - The helical tomotherapy thread effect.
AB  - Inherent to helical tomotherapy is a dose variation pattern that manifests as a
      "ripple" (peak-to-trough relative to the average). This ripple is the result of
      helical beam junctioning, completely unique to helical tomotherapy. Pitch is
      defined as in helical CT, the couch travel distance for a complete gantry
      rotation relative to the axial beam width at the axis of rotation. Without
      scattering or beam divergence, an analytical posing of the problem as a simple
      integral predicts minima near a pitch of 1/n where n is an integer. A convolution
      superposition dose calculator (TomoTherapy, Inc.) included all the physics needed
      to explore the ripple magnitude versus pitch and beam width. The results of the
      dose calculator and some benchmark measurements demonstrate that the ripple has
      sharp minima near p=0.86(1/n). The 0.86 factor is empirical and caused by a beam
      junctioning of the off-axis dose profiles which differ from the axial profiles as
      well as a long scatter tail of the profiles at depth. For very strong intensity
      modulation, the 0.86 factor may vary. The authors propose choosing particular
      minima pitches or using a second delivery that starts 180 deg off-phase from the
      first to reduce these ripples: "Double threading." For current typical pitches
      and beam widths, however, this effect is small and not clinically important for
      most situations. Certain extremely large field or high pitch cases, however, may
      benefit from mitigation of this effect.

PMID- 15984693
TI  - Recommendations of the American Association of Physicists in Medicine regarding
      the impact of implementing the 2004 task group 43 report on dose specification
      for 103Pd and 125I interstitial brachytherapy.
AB  - In March 2004, the recommendations of the American Association of Physicists in
      Medicine (AAPM) on the interstitial brachytherapy dosimetry using 125I and 103Pd
      were reported in Medical Physics [TG-43 Update: Rivard et al., 31, 633-674
      (2004)]. These recommendations include some minor changes in the dose-calculation
      formalism and a major update of the dosimetry parameters for eight widely used
      interstitial brachytherapy sources. A full implementation of these
      recommendations could result in unintended changes in delivered dose without
      corresponding revisions in the prescribed dose. Because most published clinical
      experience with permanent brachytherapy is based upon two widely used source
      models, the 125I Model 6711 and 103Pd Model 200 sources, in this report we
      present an analysis of the dosimetric impact of the 2004 TG-43 dosimetry
      parameters on the history of dose delivery for these two source models. Our
      analysis indicates that the currently recommended prescribed dose of 125 Gy for
      Model 200 103Pd implants planned using previously recommended dosimetry
      parameters [AAPM 103Pd dose prescription: Williamson et al., Med. Phys. 27, 634
      642 (2000)] results in a delivered dose of 120 Gy according to dose calculations
      based on the 2004 TG-43 update. Further, delivered doses prior to October 1997
      varied from 113 to 119 Gy for a prescribed dose of 115 Gy compared to 124 Gy
      estimated by the AAPM 2000 report. For 125I implants using Model 6711 seeds,
      there are no significant changes (less than 2%). Practicing physicians should
      take these results into account when selecting the clinically appropriate
      prescribed dose for 103Pd interstitial implant patients following implementation
      of the 2004 TG-43 update dose-calculation recommendations. The AAPM recommends
      that the radiation oncology community review this report and consider whether the
      currently recommended dose level (125 Gy) needs to be revised.

PMID- 15984694
TI  - "Dose distribution close to metal implants in gamma knife radiosurgery: a Monte
      Carlo study" [Med. Phys. 30, 1812-1815 (2003)].

PMID- 15984695
TI  - Hand-assisted laparoscopic surgery (HALS): a bridge to complex laparoscopic
      procedures.

PMID- 15984696
TI  - Physical reality simulation for training of laparoscopists in the 21st century. A
      multispecialty, multi-institutional study.
AB  - BACKGROUND: Simulation is the most effective and safe way to train laparoscopic
      surgeons in an era of limited work hours, lack of funding, and increasing
      malpractice costs. However, the costs associated with the use of virtual reality
      simulators are significant, and although very technically sophisticated they
      still lack tactile feedback. We are proposing a physical reality simulator, the
      LTS 2000, as a reliable and effective alternative to virtual reality. This study
      was carried out to establish how reliably the simulator was able to differentiate
      between different levels of laparoscopic experience and to analyze the detection
      of skills improvement after simulation and clinical training. METHODS: This study
      was carried out, between July 2002 and August 2003, in the departments of Surgery
      and Obstetrics and Gynecology at 2 separate institutions. We enrolled 40
      individuals in the study who had experience ranging from postgraduate year-1 to
      full-time faculty level. Five postgraduate year-3 residents were subsequently
      retested after rotating on clinical services, performing advanced laparoscopic
      procedures to assess whether the simulator was sensitive enough to detect
      improvements in laparoscopic skills at the intermediate level. Six tasks were
      included in the test, and they were scored for speed and precision with the
      McGill system. Two scores were obtained: a coordination score and a suturing
      score combined in a total score. Other variables analyzed were handedness,
      specialty, number of laparoscopic procedures performed, and hours spent on the
      simulator. RESULTS: Forty-five tests were performed. The number of subjects in
      each group based on level of experience was equally distributed. No difference
      occurred in scores between institutions, specialty, and right- or left-handed
      surgeons. A significant increase occurred in the coordination score and suturing
      score combined in the total score with increasing experience (P < 0.05) at each
      level. Furthermore, the simulator was sensitive enough to detect a significant
      difference in all 3 scores between subjects who had practiced with the simulator
      before being tested (P < 0.05). The scores of the 5 postgraduate year-3
      participants doubled when tested, without reaching statistical significance due
      to the small sample size. CONCLUSIONS: Our study shows that the LTS 2000 reliably
      and reproducibly detects different levels of laparoscopic expertise and
      progression of the learning curve. LTS 2000 as a model of physical reality
      simulation should be considered a reliable alternative to virtual reality
      simulation.

PMID- 15984697
TI  - Objective assessment of gastrointestinal endoscopy skills using a virtual reality
      simulator.
AB  - BACKGROUND: This study was carried out to validate the role of virtual reality
      computer simulation as a method of assessment of psychomotor skills in
      gastrointestinal endoscopy. We aimed to investigate whether the GI Mentor II
      computer system (Simbionix Ltd.) was able to differentiate between subjects with
      different experience with GI endoscopy. METHODS: Twenty-eight subjects were
      included in the study. They were divided into 3 groups according to their
      experience with GI endoscopy: experienced [group 1, performed > 200 endoscopic
      procedures, (n = 8)] residents [group 2, performed < 50 endoscopic procedures, (n
      = 10)] and medical students [group 3, never performed GI endoscopy, (n = 10)].
      All participants received identical pretest instruction on the simulator.
      Assessment of endoscopic skills was performed during a simulated colonoscopy and
      was based on parameters measured by the computer system: time, percentage of
      mucosa surface examined, efficiency of screening, time with a clear view,
      excessive local pressure, pain, time with pain, loop formation, and total time
      with a loop. RESULTS: Significant differences in performance existed between
      surgeons in the 3 groups. Experienced surgeons demonstrated best performance
      parameters, followed by the residents and the medical students. Significant
      differences in time (Kruskal-Wallis test, P < 0.001), percentage of mucosa
      surface examined (P = 0.001), efficiency of screening (P = 0.001), time with a
      clear view (P = 0.001), pain experienced (P = 0.004), time with pain (P = 0.012),
      loop formation (P < 0.001), time with a loop (P < 0.001), and excessive local
      pressure (P = 0.001) were demonstrated. Significant differences existed between
      group 1 and 2 and 1 and 3 (Mann-Whitney test, P < 0.05). Differences between
      groups 2 and 3 did not reach statistical significance (P > 0.05). CONCLUSIONS:
      The VR simulator was able to differentiate between subjects with different
      endoscopic experience. This indicates that the GI Mentor measures skills relevant
      for gastrointestinal endoscopy and can be used in training programs as an
      assessment tool.

PMID- 15984698
TI  - Effects of a laparoscopic course on student interest in surgical residency.
AB  - BACKGROUND: The number of surgical residency applicants has been declining. Early
      introduction of the discipline of surgery is thought to stimulate early interest
      in surgical residency. This study investigated the hypothesis that a laparoscopic
      skills course introduced in preclinical years would stimulate student interest in
      entering surgical residency. METHODS: Preclinical medical students participated
      in a laparoscopic skills training course. All students underwent an animate
      laboratory at the beginning and at the end of the course. Students were divided
      into 4 separate groups: virtual reality, box trainer, both trainers, and control
      group. Before and after the course, students were asked their residency interest.
      First- and second-year medical students participated in the course. RESULTS:
      Before the course, 56% of the students desired to go into general surgery or a
      surgical subspecialty. After the course, 49% of the students expressed interest
      in entering general surgery or a surgical subspecialty. A decrease occurred in
      students who desired to go into surgical subspecialty residency from 31% to 15%
      (P = NS), and an increase occurred in students who desired to go into general
      surgery residency from 25% to 34% (P = NS). No statistically significant
      difference was seen in the 4 individual training subgroup analyses. CONCLUSIONS:
      Participation in a laparoscopic skills course does not affect medical student
      interest in entering surgical residency. A trend was noted in students choosing
      general surgery over surgical subspecialty training after this course. Surgical
      educators need to investigate methods to encourage preclinical medical student
      interest in surgical residencies.

PMID- 15984699
TI  - Diagnosis and laparoscopic repair of type I obturator hernia in women with
      chronic neuralgic pain.
AB  - BACKGROUND: We performed a pilot study review of 7 female patients suffering with
      obturator neuralgia produced by a type I obturator hernia. Diagnosis and
      laparoscopic treatment of this rare hernia are presented. METHODS: Patients with
      chronic pelvic pain and signs of obturator neuralgia were identified
      retrospectively by chart review. These patients had been referred to our chronic
      pelvic pain clinic. Outcomes of their surgery from February through November 2001
      were analyzed. Median length of follow-up was 11 months (range, 6 to 16). A new
      technique using Cooper's ligament and arcus tendineus fasciae pelvis was used for
      the tension-free mesh hernia repair. RESULTS: In this pilot study, 6 of 7
      patients (86%) received greater than 50% relief of their chronic pelvic pain,
      which leads to the conclusion that we have at least 95% confidence that the pain
      reduction achieved is greater that 50%. Due to the small sample size, no
      statistically meaningful conclusions could be reached. All of the patients have
      reported some pain relief and increased function since surgery. CONCLUSION:
      Symptomatic type I obturator hernias may be more common than previously thought.
      Patients with obturator neuralgia, persisting longer than 6 months despite
      conservative therapy, may respond to laparoscopic reduction of the pilot fat tag
      and mesh overlay of the obturator canal.

PMID- 15984700
TI  - Mediastinoscopy in the treatment of mediastinal cysts.
AB  - OBJECTIVE: Primary cysts constitute 25% of all masses in the mediastinum. Because
      radiological investigations are often inconclusive, many adults require
      mediastinoscopy, thoracotomy, video-assisted thoracic surgery, or computed
      tomography-guided transbronchial, transesophageal, or transcutaneous aspiration
      to confirm the cystic nature of these lesions. Minimally invasive procedures fail
      when the cyst contents are gelatinous and mucoid (failure to aspirate) or when
      the cyst wall continues to secrete fluid. Though Pursel reported mediastinoscopic
      extirpation of benign cysts 35 years ago, it remains a "therapeutic curiosity"
      with sporadic reports of its usage. We report 2 successful mediastinal cyst
      extirpations performed as outpatient procedures and review the literature with
      regards to its management. METHODS: A rigid, 8-mm mediastinoscope was inserted
      into the anterior mediastinum following the creation of a 2-cm suprasternal
      incision and dissection along the anterior surface of the trachea. After
      aspiration, cytology of the contents revealed their benign nature. Right
      paratracheal cysts in 2 adult males were successfully removed
      mediastinoscopically by blunt and sharp dissection. RESULTS: Histopathology
      revealed benign mesothelial cysts in both instances. Both patients had an
      uncomplicated procedure and were discharged within 23 hours. No other pathology
      was detected on mediastinoscopy, and follow-up at 3 months and 6 months has
      revealed no recurrence. CONCLUSION: Mediastinoscopic cyst removal is a minimally
      invasive procedure with a very low morbidity and mortality rate. Morbidity,
      recovery, and discharge times are much less than those of more invasive
      procedures (video-assisted thoracic surgery / thoracotomy). We suggest that it
      should be the first-choice procedure for the excision of appropriately located
      benign mediastinal cysts.

PMID- 15984701
TI  - Preliminary experience with robot-assisted laparoscopic staging of gynecologic
      malignancies.
AB  - OBJECTIVE: To evaluate the feasibility of integrating robot-assisted technology
      in the performance of laparoscopic staging of gynecologic malignancies. METHODS:
      Seven patients underwent robot-assisted laparoscopic staging procedures for
      gynecologic cancers. Data were collected and analyzed as a retrospective case
      series analysis. RESULTS: We attempted 7 robot-assisted laparoscopic staging
      procedures with no conversions to laparotomy. The median lymph node count for
      lymphadenectomy was 15 (range, 4 to 29). Mean operating time was 257 minutes
      (range, 174 to 345). The average estimated blood loss was 50 mL. One patient
      developed sinusitis and required intravenous antibiotics. The median hospital
      stay was 2 days. CONCLUSION: Robot-assisted laparoscopic staging is a feasible
      technique that may overcome the surgical limitations of conventional laparoscopy.

PMID- 15984702
TI  - A safer, simpler, classic intrafascial supracervical hysterectomy technique.
AB  - OBJECTIVES: Our aim is to introduce the technical aspects and advantages of a new
      classic intrafascial supracervical hysterectomy (CISH) technique over the
      conventional technique. METHODS: We performed a retrospective evaluation
      (Canadian Task Force classification II-2) of 200 women who underwent conventional
      CISH technique (100 cases), between March 2000 and September 2000, or the new
      CISH technique (100 cases) between May 2002 and November 2002. The charts of
      these 200 women were reviewed regarding patient characteristics, indications,
      uterine weight, estimated blood loss, operating time, and hemoglobin change.
      RESULTS: The women who underwent the new CISH had significantly shorter operating
      time as compared with operating time for the conventional method. Although no
      significant difference existed in the estimated blood loss, the hemoglobin
      change, which is an objective sign of blood loss, was significantly smaller using
      the new CISH technique than using the conventional CISH technique. CONCLUSIONS:
      The new CISH technique is safer, more convenient, faster, and results in less
      blood loss than the conventional technique, especially when the uterus is
      markedly enlarged by a large myoma, the ovarian ligament is too short, or the
      ovary and uterus are very closely adherent.

PMID- 15984703
TI  - A ten-year, single institution experience with laparoscopic splenectomy.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic splenectomy (LS) is now widely performed
      and is considered the standard of care for the treatment of certain diseases of
      the spleen. Although multiple studies have documented the safety and feasibility
      of laparoscopic splenectomy, little long-term data are available. We present a 10
      year, single institution experience with laparoscopic splenectomy to determine
      trends in procedural outcome data. METHODS: Laparoscopic splenectomy was
      performed in 109 consecutive, unselected patients with benign or malignant
      hematological diseases from March 1992 to November 2001. A prospective,
      longitudinal database, medical record review, and patient interviews were used
      for data acquisition. During the last 10-years, the annual number of laparoscopic
      splenectomy was relatively constant. Therefore, patients were divided into 2
      cohorts, comparing the first 55 consecutive patients (Group I) with the
      subsequent 54 patients (Group II) who underwent LS. Data were analyzed using the
      unpaired Student t test, with values of P < 0.05 considered significant. RESULTS:
      Mean patient age was 39 years (range, 6 to 79) in Group I and 45 years (range, 13
      to 77) in Group II. Total operative time was 151 minutes in Group I and 159
      minutes in Group II (NS), estimated blood loss averaged 544 mm in Group I and
      308mm in Group II (P = 0.015). The mean specimen weight of the spleen was 288 g
      in Group I and 512 g in Group II (P = 0.03). Morbidity occurred in 7 of the first
      55 patients (13%) and 5 of the next 54 patients (9%). Additionally, 7 conversions
      to an open operation were necessary in Group I (13%) versus only 1 conversion in
      Group II (2%). CONCLUSION: A decade of experience with LS shows that it can be
      performed safely for a wide variety of indications. Over the last 10 years, the
      average spleen size has increased, yet a significant reduction in blood loss and
      conversion rate has been achieved.

PMID- 15984704
TI  - Gangrenous cholecystitis in the decade before and after the introduction of
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Gangrenous cholecystitis is a severe form of acute cholecystitis with
      high morbidity. This study investigate the outcomes for patients undergoing
      cholecystectomy for gangrenous cholecystitis in the decade before and after the
      introduction of laparoscopic technology at our institution. METHODS: From 1982 to
      2002, all patients undergoing cholecystectomy for gangrenous cholecystitis were
      prospectively entered into a database. Demographic data, method of surgery, and
      outcome variables were assessed and compared over time. RESULTS: Cholecystectomy
      was performed to treat gangrenous cholecystitis in 238 patients (mean age, 54
      years). From 1982 to 1992, 98 patients underwent cholecystectomy for gangrenous
      cholecystitis, and from 1992 to 2002, 140 patients underwent the procedure.
      Ninety-seven patients underwent laparoscopic cholecystectomy, and 33 patients
      (34%) required conversion. The open and laparoscopic cholecystectomy group
      differed in the number of intensive care unit admissions (13% vs. 5%, P < 0.05),
      overall length of hospital stay (10 vs. 5.7 days, P < 0.001) and rate of
      intraabdominal abscesses (8% vs. 0.7%). CONCLUSION: Gangrenous cholecystitis
      remains a disease with high morbidity. Laparoscopic cholecystectomy shortened
      hospital stay and can be offered without increasing morbidity. Methods to
      decrease intraabdominal abscess formation in patients undergoing laparoscopic
      cholecystectomy for gangrenous cholecystitis are needed.

PMID- 15984705
TI  - Actual time required for dynamic fluoroscopic intraoperative cholangiography.
AB  - OBJECTIVES: This study was undertaken to determine the actual amount of time a
      dynamic fluoroscopic intraoperative cholangiogram adds to a laparoscopic
      cholecystectomy. A secondary objective was to define the information gained from
      this procedure. METHODS: A consecutive case study of 52 patients undergoing
      laparoscopic cholecystectomy was used. Time was recorded from placement of a
      laparoscopic hemoclip across the cystic duct at its junction with the gallbladder
      until successful completion of the intraoperative cholangiogram. The mean,
      median, and range of times for these cases, as well as the results and false
      negative rates, were determined. RESULTS: Cholangiography was successfully
      completed in 96% of patients. The mean time added to laparoscopic cholecystectomy
      by the addition of dynamic fluoroscopic intraoperative cholangiography was 4.3
      minutes. The median time was 3.0 minutes. The times ranged from 2.0 minutes to
      16.0 minutes. Choledocholithiasis was present in 15.4% of these patients. The
      false-positive rate was zero in this study. CONCLUSIONS: Dynamic fluoroscopic
      intraoperative cholangiogram was fast and efficient. The information gained was
      significant in that 15% of patients proceeded on to laparoscopic common bile duct
      exploration. We conclude that intraoperative cholangiography should be a routine
      addition to laparoscopic cholecystectomy.

PMID- 15984706
TI  - Laparoscopic cholecystectomy in patients with previous abdominal surgery.
AB  - BACKGROUND: Laparoscopic cholecystctomy has become the treatment of choice for
      symptomatic gallstones. The potential risks have dissuaded some surgeons from
      using the laparoscopic procedure in patients with previous abdominal surgery.
      Therefore, we aimed to investigate the effect of previous abdominal surgery on
      the feasibility and safety of laparoscopic cholecystectomy. METHODS: This study
      included 600 well-documented patients with gallstones who underwent laparoscopic
      cholecystctomy at our surgical department between May 2000 and January 2004. The
      patients were classified into 3 groups: group 1, patients without a history of
      previous abdominal surgery (n = 408); group 2, patients with a history of upper
      abdominal surgery (n = 92); group 3, patients with a history of lower abdominal
      surgery (n = 100). The data were collected and analyzed for open conversion
      rates, operative times, perioperative and postoperative complications, and
      hospital stay. RESULTS: Of the 600 study patients, 192 had undergone previous
      abdominal surgery (92 upper, 100 lower). Conversion rate, hospital stay, and
      complication rates were similar in each group. Mean operating time was the
      longest (57 +/- 9.8 min) in patients with previous upper abdominal surgery (P <
      0.05). On the other hand, the operative time was similar in groups 1 and 3 (P >
      0.05). CONCLUSION: Previous abdominal surgery is not a contraindication to safe
      laparoscopic cholecystectomy. However, previous upper abdominal surgery is
      associated with a prolonged operation time.

PMID- 15984707
TI  - Laparoscopic-assisted colon resections: long-term results and survival.
AB  - OBJECTIVE: We reviewed the long-term results and patient survival for
      laparoscopic-assisted resection of colorectal malignancies. The place of
      laparoscopic colectomy for colorectal carcinomas is controversial. The techniques
      and expected surgical outcomes for patients undergoing laparoscopic and
      laparoscopic-assisted colectomies are being defined as these procedures become
      more acceptable and reach parity with, or even surpass, results of traditional
      operations. Anecdotal reports in the literature describe port-site and incisional
      tumor implantation in patients undergoing laparoscopic-assisted colectomies for
      colorectal malignancies. This raises concerns about whether these incisional
      tumor sites are more common in these patients and whether their survival is
      compromised by the laparoscopic technique. METHODS: The authors reviewed data
      from 110 patients who underwent laparoscopic-assisted colectomies for colorectal
      cancer to determine the long-term results and survival and to compare the safety
      and efficacy of laparoscopic-assisted colectomy to the safety and efficacy of
      open colectomy. Between July 1991 and June 1999, 350 patients underwent
      laparoscopic-assisted colectomies. Of these, 110 patients had colorectal
      malignancies. Survival rates and patterns of recurrence were compared within the
      various TNM stages and compared with conventional data after open surgery. The
      American Joint Committee on Cancer staging for colorectal carcinomas and the
      Kaplan-Meier method were used to determine the survival curves. RESULTS:
      Laparoscopic-assisted colon resections for colorectal malignancies were performed
      in 110 patients. Fifty-one percent of the patients were women, and 49% percent
      were men, with a mean age of 78.17 years. The mean follow-up was 43 months.
      Thirteen patients were converted to open operation due to various difficulties
      encountered during the procedure. Mean operative time was 128.16 minutes, and
      mean hospital stay was 6.91 days. Perioperative mortality was 2.77%. There were 4
      local recurrences. The ten-year survival rates for the various stages were 78%
      for stage I, 33% for stage II, 30% for stage III, and 0% for stage IV. No port
      site implantations occurred. CONCLUSION: Laparoscopic-assisted colon resection of
      colorectal carcinomas is technically feasible and safe. It allows earlier
      postoperative recovery and a shorter hospital stay. The long-term survival is
      also satisfactory. The incidence of port-site implants is no more than that with
      the conventional open technique. Determination of any benefits over the
      conventional open technique, however, still await prospective randomized trials.

PMID- 15984708
TI  - Results of laparoscopic versus open abdominal and incisional hernia repair.
AB  - BACKGROUND: Incisional hernia is a frequent complication of abdominal surgery.
      The object of this study was to confirm the safety, efficacy, and feasibility of
      laparoscopic treatment of abdominal wall defects. METHODS: Fifty consecutive
      laparoscopic abdominal and incisional hernia repairs from September 2001 to May
      2003 were compared with 50 open anterior repairs. RESULTS: The 2 groups were not
      different for age, body mass index, or American Society of Anaesthesiologists
      scores. Mean operative time was 59 minutes for the laparoscopic group, 164.5
      minutes for the open group. Mean hernia diameter was 10.6 cm for the laparoscopic
      group, 10.5 cm for the open group. Mean length of stay was 2.1 days for the
      laparoscopic group, 8.1 days for the open group. Complications occurred in 16% of
      the laparoscopic and 50% of open group. Median follow-up was 9.0 months for the
      laparoscopic group, 24.5 months for the open group. Recurrence rates were 2% for
      laparoscopic group and 0% for the open group. CONCLUSION: Results for
      laparoscopic abdominal and incisional hernia repair seem to be superior to
      results for open repair in terms of operative time, length of stay, wound
      infection, major complications, and overall hospital reimbursement.

PMID- 15984709
TI  - Incisional hernia following hand-assisted laparoscopic surgery for renal cell
      cancer.
AB  - OBJECTIVES: For renal cell cancer, the hand-assisted laparoscopic approach
      provides several advantages while maintaining equal advantages with regards to
      patient recovery. We offer our experience with laparoscopic hand-assisted radical
      nephrectomy and the incidence of ventral wall hernia. METHODS: Between February
      1999 and July 2002, we performed 50 laparoscopic hand-assisted radical
      nephrectomies. A midline or a muscle splitting right lower quadrant incision was
      used depending on the side of the tumor. Hand-port incisions were all between 7
      cm and 8 cm and closed with #1 polydioxanone sulfate suture in a running fashion.
      Three (6%) patients developed hand-port incisional hernias. All hernias occurred
      in midline hand-port sites. The average body weight of those who developed an
      incisional hernia was 137 kg. Although the cause of incisional hernia is
      multifactorial, we believe that obesity plays a significant role. The technical
      limitations involved in closing a short, deep ventral incision combined with the
      earlier return to activity of laparoscopy patients put this patient population at
      significant risk. CONCLUSION: We now perform an interrupted closure with
      nonabsorbable suture for the hand-assist incision and limited activity for 4
      weeks to 6 weeks post procedure in high-risk patients. We have had no further
      wound hernias since adopting these changes.

PMID- 15984710
TI  - Laparoscopic nephron-sparing surgery for the small exophytic renal mass.
AB  - OBJECTIVES: Nephron-sparing surgery has emerged as the treatment of choice for
      the incidentally detected small renal mass, especially those less than 4 cm in
      size. We describe our technique and experience with the laparoscopic excision of
      these lesions. METHODS: Between June 2001 and October 2003, 20 patients underwent
      nephron-sparing surgery at our institution. Twenty-one laparoscopic partial
      nephrectomy procedures were performed. All tumors were detected incidentally by
      cross-sectional imaging. All patients had a solid renal mass or a complex cystic
      renal mass of Bosniak category III or greater. All solid tumors were exophytic
      and less than 4cm in diameter. Both transperitoneal and retroperitoneal
      approaches were used. Hemostasis was achieved without hilar control in 20 of the
      21 cases. RESULTS: Twenty renal units were approached transperitoneally, and 1
      retroperitoneally. Mean tumor size was 2.6 cm (range, 1.2 to 4). Mean estimated
      blood loss was 211 mL (range, 50 to 500), and mean operative time was 165
      minutes. Pathology revealed renal cell carcinoma in 14 (70%). No intraoperative
      complications occurred. Two patients required blood transfusions postoperatively.
      CONCLUSION: Carefully selected patients with small, exophytic renal masses can
      safely undergo laparoscopic excision. When achievable, this procedure can be a
      more logical alternative to ablative techniques for the minimally invasive
      management of such lesions.

PMID- 15984711
TI  - Routine postoperative chest x-ray following laparoscopic nephrectomy.
AB  - PURPOSE: To determine whether a routine postoperative chest x-ray is required
      following uneventful laparoscopic nephrectomy to rule out pneumothorax. METHODS:
      From June 1999 to May 2003, 308 laparoscopic nephrectomy cases were performed by
      5 different surgeons. This consisted of 121 radical nephrectomies, 106 donor
      nephrectomies, 29 simple nephrectomies, 29 partial nephrectomies, and 23
      nephroureterectomies. Of the 308 procedures, 186 postoperative chest x-ray s were
      obtained in the recovery room: 183 routinely and 3 for known intraoperative
      diaphragmatic injuries. Routine chest x-rays were not obtained in 122 cases due
      to the individual surgeon's preference. Of these 122 patients, 15 underwent chest
      x-ray performed while hospitalized secondary to pulmonary issues or fever.
      RESULTS: Of the 308 cases, 4 pneumothoraces were identified on chest x-ray. Three
      were identified in the patients who had intraoperative identification of
      diaphragmatic injury. The fourth pneumothorax was identified in a patient who did
      not have a routine postoperative chest x-ray but did have a chest x-ray obtained
      due to postoperative shoulder pain. The pneumothorax in this patient resolved
      spontaneously. No incidental findings existed of pneumothorax in any patient who
      underwent routine postoperative chest x-ray. CONCLUSION: In our series, a
      pneumothorax was identified either intraoperatively or based on postoperative
      clinical findings. None of the 183 routine postoperative chest x-rays changed
      patient management. Routine postoperative chest x-ray is not necessary in
      uncomplicated laparoscopic nephrectomy.

PMID- 15984712
TI  - Carbon dioxide gas heating inside laparoscopic insufflators has no effect.
AB  - BACKGROUND AND OBJECTIVES: Within recent years, the insufflation technique for
      laparoscopy has become more important with high flow insufflators (> or = 30
      L/min) and high gas turn over (> or = 800 L/procedure). Increased amounts of
      carbon dioxide (CO2) gas used can lead to laparoscopic hypothermia. We studied
      the insufflator with versus insufflators without internal gas heating (inside
      insufflator) as a sufficient method of hypothermia prevention at different flow
      rates. METHODS: With a computer-based data acquisition model, different standard
      insufflators with internal gas heating (Snowden Pencer) vs. without (Storz
      Endoflator, Storz Laparoflator, Richard Wolf, and BEI Medical) were compared
      regarding CO2 gas temperature at different points in the insufflation system
      (insufflator exit, insufflation hose end). RESULTS: Gas temperature of the
      Snowden Pencer insufflator, which is flow-rate dependent, increases at the exit
      (max. 35.4 degrees C). However, gas temperature is back to room temperature (
      0.22 to +1.10 degrees C) at the end of the insufflation hose (10 ft or 3 m) for
      all 5 insufflators studied. Even at high gas flow rates (< or = 20 L/min), CO2
      gas is at room temperature when it reaches the patient. DISCUSSION: No difference
      was noted regarding gas temperature between the insufflators compared.
      Insufflator internal gas heating, such as the Snowden Pencer insufflator, can not
      have a clinically significant effect because it is too far away from the patient
      to raise the gas temperature in the abdomen. Purchasers are misled because the
      gas-heating device has no measurable benefit for the patient.

PMID- 15984713
TI  - Laparoscopic partial gastrectomy for the treatment of gastropleural fistula.
AB  - Gastropleural fistulas (GPF) are uncommon and can occur as a consequence of prior
      pulmonary surgery, trauma, or malignancy. Conservative management usually fails,
      requiring gastrectomy and even thoracotomy in these often debilitated patients.
      We present a patient with GPF confirmed by upper endoscopy and radiographic
      contrast examination, who underwent a laparoscopic partial gastrectomy and
      closure of the fistula. To our knowledge, this is the first such report in the
      English language literature. Laparoscopic treatment of GPF may be associated with
      less early morbidity and should be considered as the initial procedure of choice.

PMID- 15984714
TI  - Postlaparoscopic cholecystectomy bile leak secondary to an accessory duct of
      Luschka.
AB  - Complications produced by the sectioning of a nonvisualized duct of Luschka are
      uncommon during laparoscopic cholecystectomy. From 1999 through 2003, we
      performed 1351 laparoscopic cholecystectomies in our department and observed 2
      cases (0.15%) of bile leakage due to duct of Luschka injury. Injury during
      laparoscopic cholecystectomy is usually produced by an excessively deep plane of
      dissection and by the anatomical localization of this accessory duct. Clinical
      symptoms are scarce after duct of Luschka injury. Numerous diagnostic methods
      have been used to detect these injuries. Nevertheless, careful clinical
      examination is still of the utmost importance. Noninvasive treatments are usually
      effective. In patients who present with acute abdomen, as in our cases, or who
      are not cured by noninvasive treatments, exploratory laparotomy is the best
      approach. The surgical treatment consists of a lavage of the abdominal cavity,
      closure of the duct of Luschka, and intraoperative cholangiography to confirm
      that the biliary tree is intact.

PMID- 15984715
TI  - A new technique to assist in difficult bile duct cannulation at the time of
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND AND OBJECTIVES: At the time of endoscopic retrograde
      cholangiopancreatography, deep cannulation of the bile duct is a prerequisite to
      be able to provide endoscopic therapy. We describe a simple technique to assist
      in difficult bile duct cannulation. METHODS: If the pancreatic duct is easily
      entered but the bile duct cannot be accessed, a guidewire is advanced into the
      pancreatic duct, and the cannulating catheter is removed leaving the tip of the
      wire in the mid pancreatic duct. Alongside the pancreatic wire, a catheter,
      preloaded with a second wire, is advanced via the channel of the endoscope. With
      the first wire in the pancreatic duct, the second wire is advanced above it in
      the anticipated bile duct axis. RESULTS: We have used this technique in 12 cases
      and succeeded in 10. No complications occurred. DISCUSSION: Inserting a
      pancreatic wire can assist in bile duct cannulation, by straightening and
      stabilizing the papilla. The use of this new technique can reduce the need for
      precut sphincterotomy, with its inherent increased risks of pancreatitis,
      bleeding, and perforation. The approach proposed by us can assist in any
      difficult bile duct cannulation, but it can be particularly useful when dealing
      with a papilla that is very prominent with a tortuous intraduodenal segment or a
      papilla located in a duodenal diverticulum.

PMID- 15984717
TI  - Laparoscopic resection of a gastric diverticulum: a case report.
AB  - A 30-year-old woman presented with halitosis, sour taste, bloating, and right
      sided abdominal pain of 3-months' duration. An upper gastrointestinal series
      revealed a diverticulum in the posterior cardia of the stomach. The patient
      underwent a laparoscopic resection of the diverticulum. Postoperatively, the
      patient did well; at a 28-month follow-up, no further symptoms were reported.
      Laparoscopic removal of a diverticulum produced an excellent outcome.

PMID- 15984716
TI  - Littoral cell angioma of the spleen treated by laparoscopic splenectomy.
AB  - Massive splenomegaly due to multifocal littoral cell angioma was discovered
      incidentally in a 55-year-old man during a workup for an unrelated condition. The
      tumor was removed successfully by laparoscopic splenectomy. We report the second
      case of littoral cell angioma of the spleen treated laparoscopically.

PMID- 15984718
TI  - An unusual complication of ureteroneocystostomy discovered at laparoscopy.
AB  - BACKGROUND: Laparoscopy is an important surgical technique, and an understanding
      of normal and altered anatomy is crucial for successful surgery. We describe
      herein a patient in whom the left ureter follows an anomalous course due to
      previous surgery. METHODS: This is the case report of a 28-year-old female with a
      history of ureteral reimplantation evaluated with laparoscopy for dysmenorrhea
      and infertility. RESULTS: The left ureter followed an anomalous, transperitoneal
      course, lateral to the fallopian tube, starting at the infundibulopelivc ligament
      down to its insertion in the bladder. During its transperitoneal course, the
      ureter perforated the ileum. CONCLUSION: This case describes an anomalous course
      of the ureter presumed to be due to previous childhood surgery. As more
      individuals with a history of ureteral reimplantation reach adulthood, an
      increasing number will require abdominal, surgical procedures. An understanding
      of potential anatomic abnormalities will reduce the risk of inadvertent visceral
      damage at surgery.

PMID- 15984719
TI  - Simultaneous extraperitoneal laparoscopic radical prostatectomy and
      intraperitoneal inguinal hernia repair with mesh.
AB  - OBJECTIVE: This report depicts the feasibility of the concomitant repair of a
      large direct inguinal hernia with mesh by using the intraperitoneal onlay
      approach after extraperitoneal laparoscopic radical prostatectomy. METHODS: A 66
      year-old man with localized adenocarcinoma of the prostate was referred for
      laparoscopic radical prostatectomy. The patient also had a 4-cm right, direct
      inguinal hernia, found on physical examination. To minimize the risk of infection
      of the mesh, an extraperitoneal laparoscopic prostatectomy was performed in the
      standard fashion after which transperitoneal access was obtained for the hernia
      repair. The hernia repair was completed by reduction of the hernia sac, followed
      by prosthetic mesh onlay. In this fashion, the peritoneum separated the
      prostatectomy space from the mesh. A single preoperative and postoperative dose
      of cefazolin was administered. RESULTS: The procedure was completed with no
      difficulty. Total operative time was 4.5 hours with an estimated blood loss of
      450 mL. The final pathology revealed pT2cN0M0 prostate cancer with negative
      margins. No infectious or bowel complications occurred. At 10-month follow-up, no
      evidence existed of recurrence of prostate cancer or the hernia. CONCLUSION:
      Concomitant intraperitoneal laparoscopic mesh hernia repair and extraperitoneal
      laparoscopic prostatectomy are feasible. This can decrease the risk of potential
      infectious complications by separating the mesh from the space of Retzius where
      the prostatectomy is performed and the lower urinary tract is opened.

PMID- 15984720
TI  - Acute abdomen in a case with noncommunicating rudimentary horn and unicornuate
      uterus.
AB  - Unicornuate uterus with a rudimentary horn is the rarest congenital anatomic
      anomaly of the female genital system, causing many obstetrical and gynecologic
      complications. The frequency of this pathology is approximately 1/100 000. A
      rudimentary horn usually develops following insufficient development of mullerian
      ducts. These patients present with dysmenorrhea, dyspareunia, and chronic pelvic
      pain because of endometriosis and rarely with acute abdominal symptoms following
      distention and torsion of the noncommunicating rudimentary horn. The case of a
      patient referred for acute abdomen after distention of a noncommunicating
      rudimentary horn is presented herein.

PMID- 15984721
TI  - Laparoscopic derotation and cholecystectomy for torsion gallbladder.
AB  - Torsion of the gallbladder is an unusual cause of gangrenous cholecystitis. Even
      with the advent of recent radiological imaging modalities, the preoperative
      diagnosis of this entity remains elusive. Herein, we present a case of
      gallbladder torsion in a 76-year-old lady who successfully underwent laparoscopic
      derotation and cholecystectomy.

PMID- 15984722
TI  - Laparoscopic-assisted primary repair of a complicated ventral incisional hernia.
AB  - Postoperative wound dehiscence is a difficult problem for the general surgeon.
      Often, patients are too sick, or the wound environment is too hostile, to undergo
      primary repair. When an eventual repair is performed, a variety of methods are
      available, but most are associated with unacceptably high morbidity rates,
      specifically high incidences of recurrences and poor cosmetic outcome. We present
      here a case of postoperative wound dehiscence following a colostomy takedown
      repaired in a previously undescribed way--a laparoscopically assisted ventral
      incisional hernia repair. The method of repair is described, and the current
      literature regarding alternatives is reviewed.

PMID- 15984723
TI  - Laparoscopic treatment of hydatid cyst of the liver: a case report.
AB  - Laparoscopic surgery may be used for treating a variety of benign hepatic lesions
      in select patients. The anatomic location of the lesions are more important than
      any other peculiarity when laparoscopic management is used. The aim of this
      report is to discuss the effects and feasibility of laparoscopic treatment of
      hydatid cyst of liver. The procedure is feasible and safe, offering all the
      advantages of laparoscopic surgery.

PMID- 15984724
TI  - CDC publishes flexible draft guidelines on tuberculosis control.

PMID- 15984728
TI  - [What future for the health professionals infected with the AIDS virus?].

PMID- 15984725
TI  - Effects of form length and item format on response patterns and estimates of
      physician office and hospital outpatient department visits. National Ambulatory
      Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 2001.
AB  - OBJECTIVES: This report describes effects due to form length and/or item formats
      on respondent cooperation and survey estimates. METHODS: Two formats were used
      for the Patient Record form for the 2001 NAMCS and OPD component of the NHAMCS: a
      short form with 70 subitems and a long form with 140 subitems. The short form
      also contained many write-in items and fit on a one-sided page. The long form
      contained more check boxes and other unique items and required a two-sided page.
      The NAMCS sample of physicians and NHAMCS sample of hospitals were randomly
      divided into two half samples and randomly assigned to either the short or long
      form. Unit and item nonresponse rates, as well as survey estimates from the two
      forms, were compared using SUDAAN software, which takes into account the complex
      sample design of the surveys. RESULTS: Physician unit response was lower for the
      long form overall and in certain geographic regions. Overall OPD unit response
      was not affected by form length, although there were some differences in favor of
      the long form for some types of hospitals. Despite having twice the number of
      check boxes on the long form as the short form, there was no difference in the
      percentage of visits with any diagnostic or screening services ordered or
      provided. However, visit estimates were usually higher for services collected
      with long form check-boxes than with (recoded) short form write-in entries.
      Finally, the study confirmed the feasibility of collecting certain items found
      only on the long form. CONCLUSION: Overall, physician cooperation was more
      sensitive to form length than was OPD cooperation. The quality of the data was
      not affected by form length. Visit estimates were influenced by both content and
      item format.

PMID- 15984730
TI  - [Breast cancer, the most frequent and the deadliest of all cancers in women].

PMID- 15984731
TI  - [Around the patient: the oncologist-psychoanalyst duo].

PMID- 15984732
TI  - [Novelty seeking and risk taking behavior in adolescents].

PMID- 15984733
TI  - [Stomas in the elderly].

PMID- 15984734
TI  - [Education, follow-up and management: blood glucose self-monitoring is an
      essential behavior].

PMID- 15984735
TI  - [Destination Guadeloupe!].

PMID- 15984736
TI  - [Almotriptan. One more triptan for migraines].

PMID- 15984737
TI  - [Covert voyager. Interview by Armand Dice].

PMID- 15984743
TI  - [An emergency plan for cancer].

PMID- 15984744
TI  - [Evaluating the risk factors for decubitus ulcers, a primary step in prevention].

PMID- 15984745
TI  - [Prevention of decubitus ulcers. A long awaited study on risk reduction].

PMID- 15984746
TI  - [Knowing how to choose the best support surface for the prevention and treatment
      of decubitus ulcers?].

PMID- 15984747
TI  - [Patient isolation].

PMID- 15984748
TI  - [Diet and caries in young children].

PMID- 15984749
TI  - [Herpes].

PMID- 15984751
TI  - [Interferon beta-1a].

PMID- 15984752
TI  - [Constructing a warmer hospital. Interview by Helene Delmotte].

PMID- 15984753
TI  - [Reconstitution of cytostatic drugs in the patient's home].

PMID- 15984754
TI  - Mercury rule lets hazardous air pollutants off the hook.

PMID- 15984755
TI  - Buckyballs batter bacteria.

PMID- 15984756
TI  - The brain is defenseless against mercury.

PMID- 15984757
TI  - Hydrogen from a microbial fuel cell.

PMID- 15984758
TI  - Are permafrost landfills safe for used drilling mud?

PMID- 15984759
TI  - Will ultraclean diesel fly on U.S. roads?

PMID- 15984760
TI  - Perchlorate biodegradation for water treatment.

PMID- 15984761
TI  - Halogenated natural products in five species of Antarctic sponges: compounds with
      POP-like properties?
AB  - Purified extracts of five species of Antarctic sponges (Demospongiae:
      Kirkpatrickia variolosa, Artemisina apollinis, Phorbas glaberrima, and
      Halichondria sp. and Calcarea: Leucetta antarctica) from King George Island were
      analyzed by GC/MS for the presence of persistent and lipophilic halogenated
      compounds to identify bioaccumulative halogenated natural products. Sample
      extracts were prepared using methods identical for the determination of POPs,
      namely, microwave-assisted extraction with organic solvents, gel permeation
      chromatography, and column chromatography on deactivated silica. In addition,
      samples were treated with sulfuric acid to remove acid-destructible compounds.
      PCBs were not detectable and only traces of lindane, p,p'-DDE, and alpha-HCH were
      detected in these samples in decreasing order of abundance, underscoring their
      uncontaminated state. In contrast, 146 brominated compounds were identified by
      correct isotopic ratios m/z 79 and 81, 50% of which eluted prior to lindane
      including the most abundant peaks. Each sponge sample contained > or = 35
      brominated compounds of natural origin, 14 of which were detected in all species.
      Estimated concentrations ranged from the high ng/kg to mg/kg (air-dried weights)
      and relative distributions of the same compounds in different sponges were highly
      variable. The high abundance of these compounds relative to known anthropogenic
      pollutants strongly suggests a natural origin. Multiple mode (EI-, ECNI-, and PCI
      ) GC/MS enabled identification of an aliphatic ketone tentatively identified as
      1,1,2-tribromo-oct-1-en-3-one, present in all species but highest in Phorbas
      glaberrima. Several halogenated phenols including 2,4,6-tribromophenol were also
      abundant in Phorbas glaberrima as were halogenated anisoles in lower relative
      abundances. The halogenated phenols were analyzed without derivatization. The
      sample of Halichondria sp. contained the dibromotrichloro monoterpene MHC-1, a
      recently described environmental contaminant in fish and seals. Retrospective
      analysis of other marine samples confirmed that 2,4,6-tribromophenol was present
      in seal blubber from both the Arctic and the Antarctic. The presence of naturally
      occurring organohalogens such as 2,4,6-tribromophenol and MHC-1 in Antarctic
      marine invertebrates thus provides a link to their occurrence in marine mammals.

PMID- 15984762
TI  - ELISA as an affordable methodology for monitoring groundwater contamination by
      pesticides in low-income countries.
AB  - The traditional instrumental technology for pesticide residue analysis is too
      expensive and labor-intense to meet the regional needs concerning environmental
      monitoring. ELISA methodology was used for a pilot scale study of groundwater
      quality in an agricultural region a few kilometers southwest of Montevideo, the
      capital city of Uruguay. The study spanned 2 years and examined concentrations
      (detection limits are given in [ppb]) of two triazine herbicides (simazine [0.3]
      and atrazine [0.4]) and the carbamate insecticide carbaryl [10] and its major
      metabolite 1-naphthol [17]. In general, pesticide concentrations were below
      detection limits in the samples tested and in all cases were well below the
      maximum contaminant levels set by the U.S. EPA. 1-Naphthol was detected
      frequently by ELISA, but the assay may have tended to systematically overestimate
      this analyte. To our knowledge, this is the first study of its type in Uruguay
      and perhaps the first systematic approach to monitoring for organic pesticides in
      groundwater water sources in the temperate region of South America.

PMID- 15984763
TI  - Exposure assessment and risk characterization for perfluorooctanoate in selected
      consumer articles.
AB  - An exposure assessment and risk characterization was conducted to better
      understand the potential human health significance of trace levels of
      perfluorooctanoate (PFO) detected in certain consumer articles. PFO is the anion
      of perfluorooctanoic acid (PFOA). Concentrations of PFO in the consumer articles
      were determined from extraction tests and product formulation information.
      Potential exposures during consumer use of the articles were quantified based on
      an assessment of behavior patterns and regulatory guidance. Health benchmarks
      were developed and then compared to the exposure estimates to yield margins of
      exposure (MOEs). A simple one-compartment model was also developed to estimate
      contributions of potential consumer exposures to PFO concentrations in serum.
      While there are considerable uncertainties in this assessment, it indicates that
      exposures to PFO during consumer use of the articles evaluated in this study are
      not expected to cause adverse human health effects in infants, children,
      adolescents, adult residents, or professionals nor result in quantifiable levels
      of PFO in human serum.

PMID- 15984764
TI  - Source apportionment of organic pollutants of a highway-traffic-influenced urban
      area in Bayreuth (Germany) using biomarker and stable carbon isotope signatures.
AB  - Traffic- and urban-influenced areas are prone to enhanced pollution with products
      of incomplete combustion of fossil fuels and biomass such as black carbon or
      polycyclic aromatic hydrocarbons (PAHs). Black carbon is composed of aromatic and
      graphitic structures and may act as a carrier for pollutants such as PAHs and
      heavy metals. However, little is known about possible contributions of traffic
      derived black carbon to the black carbon inventory in soils. Similar
      uncertainties exist regarding the contribution of different pollutant sources to
      total PAH and black carbon contents. Therefore, the objective of this study was
      to quantify the importance of traffic pollution to black carbon and PAH
      inventories in soils. PAH contamination of soils adjacent to a major German
      highway in the urban area of Bayreuth with about 50,000 vehicles per day was in
      the same order of magnitude compared to highway-close soils reported in other
      studies. Using molecular (black carbon and PAHs) and compound-specific stable
      carbon isotope evidence (PAHs) it was demonstrated that this contamination
      originated not only from automobile exhausts, here primarily diesel, but also
      from tire abrasion and tailpipe soot which significantly contributed to the
      traffic-caused black carbon and PAH contamination. Low molecular weight PAHs were
      more widely transported than their heavy molecular counterparts (local
      distillation), whereas highway-traffic-caused black carbon contamination was
      distributed to at least 30 m from the highway. On the other hand, urban fire
      exhausts were distributed more homogeneously among the urban area.

PMID- 15984765
TI  - Long-term change of polycyclic aromatic hydrocarbon deposition to peatlands of
      eastern Canada.
AB  - To date, studies about historic PAH (polycyclic aromatic hydrocarbons) deposition
      at a regional scale have rarely been published. To address this research gap, we
      sampled 17 ombrotrophic peatlands across eastern Canada. The peat cores from
      hollows were dated with 210Pb for the period of about 1850-2000 and analyzed
      fortheir PAH concentration, so PAH deposition could be reconstructed. Peat
      samples were extracted by accelerated solvent extraction (ASE). The extracts were
      purified by column chromatography with aluminum oxide and silica gel. PAH were
      measured by gas chromatography-tandem mass spectrometry (GC-MS/MS). Overall
      reconstructed deposition rates of sigma-11 PAH ranged from 4 to 1432 microg m(-2)
      year(-1). Three different long-term trends in PAH deposition could be
      distinguished: sites with two separated periods of maximum PAH deposition, sites
      with one period of maximum PAH deposition, and sites with no clearly separated
      period of maximum PAH deposition. Increasing PAH depositions were caused by rapid
      industrialization accompanied by extensive use of fossil fuels; decreasing PAH
      depositions were caused by substitution of these fuels and movements of PAH
      emitting industry to different regions. At all sites either phenanthrene (20-60%)
      or benzo[b+k]fluoranthene (10-40%) was the predominant PAH. Detailed analysis of
      three bogs suggested that combustion of coal and vehicle exhausts mainly
      contributed to the peat PAH burden. The temporal trends of PAH deposition
      indicated that increases in the PAH deposition rates followed the industrial
      development in Canada, particularly in the periods 1880-1910 and 1940-1960.
      Recent abatement efforts were reflected in decreased PAH deposition rates to
      about 15% of the maximum.

PMID- 15984766
TI  - Investigation of the role of structural domains identified in sedimentary organic
      matter in the sorption of hydrophobic organic compounds.
AB  - The role of composition and structure of sedimentary organic matter (SOM) in the
      sorption of hydrophobic organic compounds (HOCs) was investigated by spiking 13C
      labeled phenanthrene onto six estuarine sediments known to vary in SOM content
      and character. After equilibration and HF treatment, 13C NMR cross polarization
      and stable carbon isotope analyses indicated that the amount of desorption
      resistant phenanthrene was related to aromatic carbon content. Application of the
      13C NMR spectral editing technique proton spin relaxation editing (PSRE)
      demonstrated that all samples consisted of a rapidly relaxing and a slowly
      relaxing component, further evidence that SOM can be described as a structurally
      heterogeneous sorbent. Further, comparison of corresponding control and spiked
      PSRE subspectra revealed that, for each of the six sediments, desorption
      resistant phenanthrene had become associated almost exclusively with the rapidly
      relaxing component. In only two of the sediments were there even small amounts of
      phenanthrene discernible in the slowly relaxing component, which is signficant as
      it was not always true that aromatic carbon was concentrated exclusively in the
      rapidly relaxing phase. The implication of these findings is that not all
      aromatic fractions have the same affinity for phenanthrene and that some
      fractions may indeed have little affinity at all. These results were interpreted
      as indicative that rapidly relaxing aromatic carbon associated with either
      sediment-associated charcoal or diagenetic organic matter plays a controlling
      role in the sorption of HOCs. However, the exact manner in which this rapidly
      relaxing aromatic phase relates to models presented elsewhere remains unclear.

PMID- 15984767
TI  - Investigations of the potential influence of environmental contaminants on the
      thymus and spleen of harbor porpoises (Phocoena phocoena).
AB  - Harbor porpoises from the German North and Baltic Seas exhibit a higher incidence
      of bacterial infections compared to whales from less polluted arctic waters. The
      potential adverse effect of environmental contaminants such as polychlorinated
      biphenyls (PCBs) and heavy metals on the immune system and the health status of
      marine mammals is still discussed controversially. The aim of the present study
      was to investigate the possible influence of PCB, polybrominated diphenyl ether
      (PBDE), toxaphene, (p,p'-dichlorodiphenyl)trichlorethane (DDT), and (p,p'
      dichlorodiphenyl)dichlorethene (DDE) on the immune system of harbor porpoises.
      Lymphoid organs are influenced by a variety of factors, and therefore special
      emphasis was given to separating the confounding effect of age, health status,
      nutritional state, geographical location, and sex from the effect of contaminant
      levels upon thymus and spleen. Contaminant analysis and detailed pathological
      examinations were conducted on 61 by-caught and stranded whales from the North
      and Baltic Seas and Icelandic and Norwegian waters. Stranded harbor porpoises
      were more severely diseased than by-caught animals. Thymic atrophy and splenic
      depletion were significantly correlated to increased PCB and PBDE levels.
      However, lymphoid depletion was also associated with emaciation and an impaired
      health status. The present report supports the hypothesis of a contaminant
      induced immunosuppression, possibly contributing to disease susceptibility in
      harbor porpoises. However, further studies are needed to determine if lymphoid
      depletion is primarily contaminant-induced or secondary to disease and emaciation
      in this cetacean species.

PMID- 15984768
TI  - Gas transport below artificial recharge ponds: insights from dissolved noble
      gases and a dual gas (SF6 and 3He) tracer experiment.
AB  - A dual gas tracer experiment using sulfur hexafluoride (SF6) and an isotope of
      helium (3He) and measurements of dissolved noble gases was performed at the El
      Rio spreading grounds to examine gas transport and trapped air below an
      artificial recharge pond with a very high recharge rate (approximately 4 m day(
      1)). Noble gas concentrations in the groundwater were greater than in surface
      water due to excess air formation showing that trapped air exists below the pond.
      Breakthrough curves of SF6 and 3He at two nearby production wells were very
      similar and suggest that nonequilibrium gas transfer was occurring between the
      percolating water and the trapped air. At one well screened between 50 and 90 m
      below ground, both tracers were detected after 5 days and reached a maximum at
      approximately 24 days. Despite the potential dilution caused by mixing within the
      production well, the maximum concentration was approximately 25% of the mean pond
      concentration. More than 50% of the SF6 recharged was recovered by the production
      wells during the 18 month long experiment. Our results demonstrate that at
      artificial recharge sites with high infiltration rates and moderately deep water
      tables, transport times between recharge locations and wells determined with gas
      tracer experiments are reliable.

PMID- 15984769
TI  - Quantitative determination of perfluorochemicals in sediments and domestic
      sludge.
AB  - Perfluorochemicals (PFCs) are the subject of increasingly intense environmental
      research. Despite their detection both in biota and in aqueous systems, little
      attention has been paid to the possible presence of this class of compounds in
      solid environmental matrixes. The limited available data indicate that some PFCs
      such as perfluorooctane sulfonate (PFOS) may strongly sorb to solids, and sewage
      sludge is widely suspected as a major sink of PFCs entering municipal waste
      streams. A quantitative analytical method was developed that consists of liquid
      solvent extraction of the analytes from sediments and sludge, cleanup via solid
      phase extraction, and injection of the extracts with internal standards into a
      high-performance liquid chromatography (HPLC) system coupled to a tandem mass
      spectrometer (LC/MS/MS). The limits of detections of the method were analyte and
      matrix dependent, but ranged from 0.7 to 2.2 ng/g and 0.041 to 0.246 ng/g (dry
      weight) for sludge and sediment, respectively. A demonstration of the method was
      performed by conducting a limited survey of domestic sludge and sediments. The
      concentration of PFCs in domestic sludge ranged from 5 to 152 ng/g for total
      perfluorocarboxylates and 55 to 3370 ng/g for total perfluoroalkyl sulfonyl-based
      chemicals. Data from a survey of San Francisco Bay Area sediments suggest
      widespread occurrence of PFCs in sediments at the low ng/g to sub-ng/g level.
      Furthermore, substances that may be transformed to PFOS, such as 2-(N
      ethylperfluorooctanesulfonamido) acetic acid (N-EtFOSAA) and 2-(N
      methylperfluorooctanesulfonamido) acetic acid (N-MeFOSAA), are present in both
      sediments and sludge at levels often exceeding PFOS.

PMID- 15984770
TI  - Determination of temperature-dependent Henry's law constants of odorous
      contaminants and their application to human perception.
AB  - A new method was developed to measure Henry's law constants at varying
      temperatures and from these data determine enthalpies of reactions for
      volatilization of aqueous compounds. The method was applied to 2-methylisoborneol
      (2-MIB), geosmin, and trans-2,cis-6-nonadienal, which are three of the major
      odorous compounds found in natural and drinking water. The method used static
      headspace equilibrium in standard odor analysis flasks and SPME-GC/MS.
      Dimensionless Henry's law constants were determined at 20, 25, 32, and 39 degrees
      C in distilled water. Their values ranged from 0.002 to 0.02 and increased with
      increasing temperature. The study was continued by determining the effects of
      different concentrations of fulvic acid added to the aqueous media. Decreases of
      5-40% in Henry's law constants were observed when fulvic acid was present;
      however the decrease was not correlated with the fulvic acid concentration.
      Fulvic acid at any concentration caused a small decrease in constants for geosmin
      and 2-MIB, yet a more substantial decrease was obtained for nonadienal. Finally,
      the gas-phase concentrations were predicted using measured Henry's law constants
      for known aqueous concentrations of 2-MIB, geosmin, and nonadienal at 25 and 45
      degrees C. An increase in the gas-phase concentration was not correlated to an
      increase in human perception as determined by a trained human panel. It is
      concluded that, after some point, panelists were not able to perceive an increase
      in the odorant concentration. This has important implications for controlling
      nuisance odors in the environment.

PMID- 15984771
TI  - Selected volatile organic compounds in residential air in the city of Ottawa,
      Canada.
AB  - Airborne levels of selected volatile organic chemicals (VOCs) that are priorities
      for exposure assessment under the Canadian Environmental Protection Act (CEPA)
      1999 were measured in both indoor air and outdoor air of 75 residential houses,
      in the city of Ottawa, Canada, during the winter of 2002/2003. The houses were
      randomly selected using Ottawa 2001 population census data. VOCs were collected
      on adsorbent tubes and measured by thermal desorption GC/MS. Among 37 chemicals
      monitored, 17 were detected with a frequency greater than 80% in indoor air; 9
      were between 30% and 80%; 7 were between 1% and 30%; and 4 were not detected.
      Concentrations of VOCs in both indoor and outdoor air are presented. Virtually
      all of the target VOCs were detected more frequently and were present at
      significantly higher levels, in indoor air than in outdoor air. As an indication
      of the contribution of indoor levels of these chemicals, ratios of the
      concentration found in indoor air to outdoor air (I/O) and the indoor source
      strength expressed in estimated emission rate per house are also presented.
      Compared with earlier published studies including a 1991/1992 Canadian national
      survey of VOCs in residential air, levels of target analytes in indoor air in
      this study were lower for a number of chemicals, indicating a possible trend
      toward decreased inhalation exposure to these chemicals in residential
      environments. This study has yielded up-to-date information on levels of a
      variety of priority airborne chemicals in residential air, which is being used to
      estimate current exposure to these substances as input to health risk assessments
      and risk management actions under CEPA 1999.

PMID- 15984772
TI  - Comparative effects of dietary methylmercury on gene expression in liver,
      skeletal muscle, and brain of the zebrafish (Danio rerio).
AB  - Effects of dietary methylmercury (MeHg) on gene expression were examined in three
      organs (liver, skeletal muscle, and brain) of the zebrafish (Danio rerio). Adult
      male fish were fed over 7, 21, and 63 days on three different diets: one control
      diet (C0: 0.08 microg of Hg g(-1), dry wt) and two diets (C1 and C2) contaminated
      by MeHg at 5 and 13.5 microg of Hg g(-1), dry wt. Total Hg and MeHg
      concentrations were determined in the three organs after each exposure duration,
      and a demethylation process was evidenced only in the liver. Thirteen genes known
      to be involved in antioxidant defenses, metal chelation, active efflux of organic
      compounds, mitochondrial metabolism, DNA repair, and apoptosis were investigated
      by quantitative real-time RT-PCR and normalized according to actin gene
      expression. Surprisingly, no change in the expression levels of these genes was
      observed in contaminated brain samples, although this organ accumulated the
      highest mercury concentration (63.5 +/- 4.4 microg g(-1), dry wt after 63 days).
      This lack of genetic response could explain the high neurotoxicity of MeHg. coxI
      and cytoplasmic and mitochondrial sod gene expressions were induced early in
      skeletal muscle and later in liver, indicating an impact on the mitochondrial
      metabolism and production of reactive oxygen species. Results demonstrated that
      skeletal muscle was not only an important storage reservoir but was also affected
      by MeHg contamination. The expression of the metallothionein mt2 and the DNA
      repair rad51 genes was up-regulated in liver between 21 and 63 days, whereas in
      skeletal muscle, mt2 remained uninduced, and gadd and rad51 were found to be
      repressed.

PMID- 15984773
TI  - Occurrence and sorption behavior of sulfonamides, macrolides, and trimethoprim in
      activated sludge treatment.
AB  - The occurrence of sulfonamide and macrolide antimicrobials, as well as
      trimethoprim, was investigated in conventional activated sludge treatment.
      Average daily loads in untreated wastewater correlated well with those estimated
      from annual consumption data and pharmacokinetic behavior. Considerable
      variations were found during a day, and seasonal differences seem to occur for
      the macrolides, probably caused by a higher consumption of these substances in
      winter. The most predominant macrolide and sulfonamide antimicrobials were
      clarithromycin and sulfamethoxazole, respectively. In the case of
      sulfamethoxazole, the main human metabolite, N4-acetylsulfamethoxazole, was
      included as an analyte, accounting for up to 86% of the total load in untreated
      wastewater. The results obtained illustrate the importance of considering
      retransformable substances, for example human metabolites, when investigating the
      behavior and fate of pharmaceuticals. Average concentrations of sulfapyridine,
      sulfamethoxazole, trimethoprim, azithromycin, and clarithromycin in activated
      sludge ranged between 28 and 68 microg/kg of dry weight. Overall the sorption to
      activated sludge was shown to be low for the investigated antimicrobials, with
      estimated sorption constants for activated sludge below 500 L/kg. Elimination in
      activated sludge treatment was found to be incomplete for all investigated
      compounds. In final effluents, the median concentrations for sulfamethoxazole and
      clarithromycin were 290 and 240 ng/L, respectively.

PMID- 15984775
TI  - Temperature and congener structure affect the enantioselectivity of toxaphene
      elimination by fish.
AB  - Recent advances in enantioselective separation techniques have enabled scientists
      to investigate environmental fate processes of chiral pollutants. In this study,
      congener- and enantiomer-specific toxaphene residues were monitored in captive,
      naturally contaminated fish (Fundulus heteroclitus) to characterize the effect of
      temperature and compound structure on the enantioselectivity of the elimination
      process. A previous study performed under warm water conditions (Tmean = 25
      degrees C) demonstrated relatively rapid (t(1/2) approximately = 7-14 d) and
      enantioselective elimination of the reductive dechlorination metabolites 2-exo,3
      endo,6-exo,8,9,-10-hexachlorobornane (B6-923 or Hx-Sed) and 2-endo,3-exo,5-endo,6
      exo,8,9,10-heptachlorobornane (B7-1001 or Hp-Sed). As expected, repetition of
      this experiment at cooler water temperatures (Tmean = 15 degrees C) resulted in a
      decrease in overall (i.e., both enantiomers) first-order elimination rate
      constants. Enantiomer fractions or ratios (EFs/ERs) during elimination, however,
      varied by congener, ranging from racemic for very rapidly eliminated Cl5
      homologues to increasingly nonracemic for selected Cl6-Cl8 homologues (including
      86-923, several unknown Cl7 compounds, B8-1414, and B8-1945). As a result, we
      propose a classification to describe the environmental persistence of chiral
      toxaphene pollutants based on congener-specific elimination kinetics and
      susceptibility to biotransformation as measured by EFs/ERs.

PMID- 15984774
TI  - Adsorption of single-ring organic compounds to wood charcoals prepared under
      different thermochemical conditions.
AB  - Environmental black carbon (BC) is believed to be an important adsorbent of
      organic pollutants. In this study, we examined the effects of changes in surface
      properties and adsorbate structure. A series of apolar compounds (cyclohexane,
      1,2-dichlorobenzene, 1,4-xylene, 1,2,3,5-tetramethylbenzene, 1,3,5
      triethylbenzene) and a series of polar compounds (o-cresol, 4-nitrotoluene, 2,4
      dinitrotoluene, and 2,4,6-trinitrotoluene) were sorbed from aqueous solution to
      maple wood char prepared under five thermochemical conditions. Two chars were
      prepared in air at 340 degrees C (C340) and 400 degrees C (C400). A subsample of
      C400 was treated with H2 in the presence of a supported Pt catalyst at 500
      degrees C (C400-H) to remove surface O. Another was treated under N2 at 500
      degrees C (C400-N) to serve as a control for C400-H. The reduced C400-H was
      further oxidized in air at 340 degrees C to reintroduce O (C400-H-A). The five
      chars vary in O content (26.1, 22.3, 4.2, 20.8, and 18.6 wt %, respectively) but
      show only minor differences in surface area and pore size distribution on the
      basis of N2 and CO2 adsorption analysis. These chars provide a basis for
      rationalizing sorption intensity as a function of sorbate molecular structure and
      surface chemistry. The following conclusions were drawn. (1) Polar interactions
      with surface O functional groups are not a significant driving force for
      adsorption. (2) When isotherms are adjusted for solute hydrophobicity (n
      hexdecane-water partition coefficient), sorption intensity of the polar compounds
      is greater than that of the apolar compounds, possibly because of pi-pi EDA
      interactions of the polar compounds with the basal plane of the graphene sheets.
      (3) The largest test compounds show steric exclusion from a portion of the
      adsorption space available to the other compounds. (4) Removal of O functionality
      by hydrogenation enhances sorption intensity of polar and apolar compounds, alike
      by reducing competitive adsorption by water molecules.

PMID- 15984776
TI  - Enhanced biodegradation of beta- and delta-hexachlorocyclohexane in the presence
      of alpha- and gamma-isomers in contaminated soils.
AB  - The chlorinated insecticide hexachlorocyclohexane (HCH) has been used extensively
      in the past, and contaminated sites are present throughout the world. Toward
      their bioremediation, we isolated a bacterium Pseudomonas aeruginosa ITRC-5 that
      mediates the degradation of all the four major isomers of HCH under aerobic
      conditions, both in liquid-culture and contaminated soils. In liquid-culture, the
      degradation of alpha- and gamma-HCH is rapid and is accompanied with the release
      of 5.6 micromole chloride ions and 4.1 micromole CO2 micromole(-1) HCH-isomer.
      The degradation of beta- and delta-isomers is slow, accompanied with the release
      of 0.9 micromole chloride ions micromole(-1) HCH-isomer, and results in a
      transient metabolite 2,3,4,5,6-pentachlorocyclohexan-1-ol. The strain ITRC-5 also
      mediates the degradation of alpha-, beta-, gamma-, and delta-isomers in
      contaminated soils, where degradation of otherwise persistent beta- and delta-HCH
      is enhanced severalfold in the presence of alpha- or gamma-HCH. The degradation
      of soil-applied beta- and delta-HCH under aerobic conditions has not been
      reported earlier. The isolate ITRC-5 therefore demonstrates potential for the
      bioremediation of HCH-wastes and contaminated soils.

PMID- 15984777
TI  - Role of hydrodynamic drag on microsphere deposition and re-entrainment in porous
      media under unfavorable conditions.
AB  - Deposition and re-entrainment of 1.1 microm microspheres were examined in packed
      glass beads and quartz sand under both favorable and unfavorable conditions for
      deposition. Experiments were performed at environmentally relevant ionic
      strengths and flow rates in the absence of solution chemistry and flow
      perturbations. Numerical simulations of experimental data were performed using
      kinetic rate coefficients to represent deposition and re-entrainment dynamics.
      Deposition rate coefficients increased with increasing flow rate under favorable
      deposition conditions (in the absence of colloid-grain surface electrostatic
      repulsion), consistent with expected trends from filtration theory. In contrast,
      under unfavorable deposition conditions (where significant colloid-grain surface
      electrostatic repulsion exists), the deposition rate coefficients decreased with
      increasing flow rate, suggesting a mitigating effect of hydrodynamic drag on
      deposition. Furthermore, the re-entrainment rate was negligible under favorable
      conditions but was significant under unfavorable conditions and increased with
      increasing flow rate, demonstrating that hydrodynamic drag drove re-entrainment
      under unfavorable conditions. The drag torque resulting from hydrodynamic drag
      was found to be 1 order of magnitude or more lower than the adhesive torque based
      on pull-off forces from atomic force microscopy measurements. This result
      indicates that hydrodynamic drag was insufficient to drive re-entrainment of
      microspheres that were associated with the grain surface via the primary energy
      minimum and suggests that hydrodynamic drag drove re-entrainment of secondary
      minimum-associated microspheres.

PMID- 15984778
TI  - Understanding the difference in oxidative properties between flame and diesel
      soot nanoparticles: the role of metals.
AB  - The purpose of this paper is to address the differences observed in the oxidative
      kinetics between flame and diesel derived soots. In particular, it has been
      observed that flame soot has a significantly higher activation energy for
      oxidation than does diesel soot. The hypothesis tested in this paper is that
      metals, possibly coming from lubricating oils, within diesel generated soot
      particles may be responsible for this effect. This is supported by the fact that
      addition of metal additives to diesel fuel is shown to have no effect on the
      activation energy of soot oxidation. The subject of this paper lies in testing
      the hypothesis by adding metal directly to a flame and extracting oxidation
      kinetics. Using a high temperature oxidation tandem differential mobility
      analyzer (HTO-TDMA) we extract particle size dependent kinetics for the oxidation
      of flame-derived soot doped with and without iron. We found that indeed addition
      of iron to a flame reduced the activation energy significantly from approximately
      162 +/- 3 kJ/mol to approximately 116 +/- 3 kJ/mol, comparable with diesel engine
      generated soot with an activation energy approximately 110 kJ/mol. These results
      are consistent with the idea that small quantities of metals during diesel
      combustion may play an important role in soot abatement.

PMID- 15984779
TI  - Effect of soil fulvic acid on nickel(II) sorption and bonding at the aqueous
      boehmite (gamma-AIOOH) interface.
AB  - The influence of soil-derived fulvic acid (SFA) on Ni(II) sorption and speciation
      in aqueous boehmite (gamma-AIOOH) suspensions was evaluated using a combination
      of sorption experiments and Ni K-edge extended X-ray absorption fine structure
      (EXAFS) spectroscopy measurements. Co-sorption of SFA at the aqueous-boehmite
      interface modifies both the extent of Ni(II) sorption as well as the local
      structure of the sorbing Ni(II) ions. In SFA-free suspensions, Ni(II) sorbs by
      forming inner-sphere bidentate mononuclear complexes with surface aluminol
      groups. Addition of SFA increases Ni(II) sorption at pH conditions below the
      sorption edge observed in SFA-free suspensions and diminishes Ni(II) sorption at
      pH above the SFA-free sorption edge. When SFA is co-sorbed to boehmite, Ni(II)
      sorbs by forming both ligand-bridging ternary surface complexes (Ni(II)-SFA
      boehmite) as well as surface complexes in which Ni(II) remains directly bonded to
      aluminol groups, that is, binary Ni(II)-boehmite or metal-bridging ternary
      surface complexes (SFA-Ni(II)-boehmite). The relative contribution of the
      individual sorption complexes depends heavily on geochemical conditions; the
      concentration of ligand-bridging complexes increases with increasing SFA sorption
      and decreasing pH. The local structure of sorbed Ni(II) does not change with
      increasing reaction time even though the extent of sorption continues to
      increase. This supports a slow uptake mechanism where surface or intraparticle
      diffusion processes are rate-limiting. This work demonstrates that the
      association of humic constituents with soil minerals can significantly modify the
      mechanisms controlling trace metal sorption and transport in heterogeneous
      aquatic environments.

PMID- 15984780
TI  - Similarities between inorganic sulfide and the strong Hg(II)-complexing ligands
      in municipal wastewater effluent.
AB  - Municipal wastewater effluent contains ligands that form Hg(II) complexes that
      are inert in the presence of glutathione (GSH) during competitive ligand exchange
      experiments. In this study, the strong ligands in wastewater effluent were
      further characterized by comparing their behavior with sulfide-containing ligands
      in model solutions and by measuring their concentration after exposing them to
      oxidants. The strong Hg(II) complexes in wastewater effluent and the complexes
      formed when Hg(II) was added to S(-II) were retained during C18 solid-phase
      extraction (SPE) and did not dissociate in the presence of up to 100 microM GSH.
      In contrast, Hg(II) complexes with dissolved humic acid were hydrophilic and
      dissociated in the presence of GSH. The combination of sulfide and humic acid
      resulted in formation of Hg(II) complexes that were inert to GSH and were only
      partially retained by C18-SPE, indicating that NOM interacted with the Hg-sulfide
      complexes. When wastewater effluent samples and model solutions of free sulfide,
      Zn-sulfide, and Fe-sulfide were exposed to 0.14 mM NaOCl for 1 h (to mimic
      conditions encountered during chlorine disinfection), the strong Hg(II)
      complexing ligands were completely removed. Exposure of the wastewater effluent
      and the model ligands to oxygen for 2 weeks resulted in approximately 60% to 75%
      loss of strong ligands. The strong ligands that remained in the oxygen-oxidized
      samples were resistant to further oxidation by chlorine, indicating that
      oxidation of S(-II) results in the formation of other sulfur-containing ligands
      such as S8 that form strong complexes with Hg(II).

PMID- 15984781
TI  - Sorption mechanisms of zinc on hydroxyapatite: systematic uptake studies and
      EXAFS spectroscopy analysis.
AB  - The systematics and mechanisms of Zn uptake by hydroxyapatite (HAP) in
      preequilibrated suspensions open to PCO2 were characterized using a combination
      of batch sorption experiments, X-ray diffraction (XRD), and extended X-ray
      absorption fine structure spectroscopy (EXAFS) over a wide range of pH and Zn
      concentrations. Sorption isotherms of Zn(II) on HAP at pH 5.0 and 7.3 show an
      initial steep slope at low Zn(II) concentrations, followed by a plateau up to
      [Zn] < approximately 750 microM, suggesting Langmuir-type behavior. At [Zn] > 750
      microM, a sharp rise in the pH 5.0 isotherm suggests precipitation, whereas
      slight continued uptake in the pH 7.3 isotherm is suggestive of an additional
      uptake mechanism. The sorption isotherm at pH 9.0 shows a steep uptake step at
      [Zn] < or = 0.8 microM, followed by an increasing linear trend up to [Zn] = 5
      microM, without any indication of a maximum, suggesting that precipitation is an
      important uptake process at this pH. Zn K edge EXAFS results show a first oxygen
      shell at 1.96-1.98 +/- 0.02 A in sorption samples with [Zn]tot < or = 250 microM
      at pH 5.0, 7.3, and 9.0, consistent with tetrahedral coordination. EXAFS results
      reveal additional P and Ca neighbors that support formation of an inner-sphere Zn
      surface complex where the Zn is coordinated to surface P04 tetrahedra in a corner
      sharing bidentate fashion, bridging a Ca atom. In contrast, EXAFS and XRD data
      indicate that precipitation of Zn3(PO4)2-4H2O (hopeite) dominates the mode of Zn
      uptake at [Zn]tot > or = 3 mM at pH 5.0. Principal component analysis and linear
      combination fits of EXAFS data reveal a mixture of inner-sphere Zn surface
      complexation and precipitation of Zn5(OH)6(CO3)2 (hydrozincite) in sorption
      samples for [Zn]tot = 5 mM at pH 7.3 and for [Zn]tot = 1 mM at pH 9.0.

PMID- 15984782
TI  - Contributions of organic peroxides to secondary aerosol formed from reactions of
      monoterpenes with O3.
AB  - The role of organic peroxides in secondary organic aerosol (SOA) formation from
      reactions of monoterpenes with O3 was investigated in a series of environmental
      chamber experiments. Reactions were performed with endocyclic (alpha-pinene and
      delta3-carene) and exocyclic (beta-pinene and sabinene) alkenes in dry and humid
      air and in the presence of the OH radical scavengers: cyclohexane, 1-propanol,
      and formaldehyde. A thermal desorption particle beam mass spectrometer was used
      to probe the identity and volatility of SOA components, and an iodometric
      spectrophotometric method was used to quantify organic peroxides. Thermal
      desorption profiles and mass spectra showed that the most volatile SOA components
      had vapor pressures similar to pinic acid and that much of the SOA consisted of
      less volatile species that were probably oligomeric compounds. Peroxide analyses
      indicated that the SOA was predominantly organic peroxides, providing evidence
      that the oligomers were mostly peroxyhemiacetals formed by heterogeneous
      reactions of hydroperoxides and aldehydes. For example, it was estimated that
      organic peroxides contributed approximately 47 and approximately 85% of the SOA
      mass formed in the alpha- and beta-pinene reactions, respectively. Reactions
      performed with different OH radical scavengers indicated that most of the
      hydroperoxides were formed through the hydroperoxide channel rather than by
      reactions of stabilized Criegee intermediates. The effect of the OH radical
      scavenger on the SOA yield was also investigated, and the results were consistent
      with results of recent experiments and model simulations that support a mechanism
      based on changes in the [HO2]/[RO2] ratios. These are the first measurements of
      organic peroxides in monoterpene SOA, and the results have important implications
      for understanding the mechanisms of SOA formation and the potential effects of
      atmospheric aerosol particles on the environment and human health.

PMID- 15984783
TI  - Surface complexation modeling of proton and Cd adsorption onto an algal cell
      wall.
AB  - This study quantifies Cd adsorption onto the cell wall of the algal species
      Pseudokirchneriella subcapitata by applying a surface complexation approach to
      model the observed adsorption behavior. We use potentiometric titrations to
      determine deprotonation constants and site concentrations for the functional
      groups on the algal cell wall. Adsorption and desorption kinetics experiments
      illustrate that adsorption of Cd onto the cell wall is rapid and reversible,
      except under low pH conditions. Adsorption experiments conducted as a function of
      pH and total Cd concentration yield the stoichiometry and site-specific stability
      constants for the important Cd-algal surface complexes. We model the acid/base
      properties of the algal cell wall by invoking four discrete surface functional
      group types, with pKa values of 3.9 +/- 0.3, 5.4 +/- 0.1, 7.6 +/- 0.3, and 9.6 +/
      0.4. The results of the Cd adsorption experiments indicate that the first,
      third, and fourth sites contribute to Cd adsorption under the experimental
      conditions, with calculated log stability constant values of 4.1 +/- 0.5, 5.4 +/-
      0.5, and 6.1 +/- 0.4, respectively. Our results suggest that the stabilities of
      the Cd-surface complexes are high enough for algal adsorption to affect the fate
      and transport of Cd under some conditions and that on a per gram basis, algae and
      bacteria exhibit broadly similar extents of Cd adsorption.

PMID- 15984784
TI  - Chemical nitrite oxidation in acid solutions as a consequence of microbial
      ammonium oxidation.
AB  - In long-term experiments with membrane aerated biofilm reactors we observed
      complete nitrite oxidation in highly concentrated ammonium nitrite solutions with
      a contaminant pH decrease to values below 3. The maximum initial concentration
      for ammonium was 42 mM and for nitrite was 41 mM. We hypothesized that (1) acid
      tolerant ammonium oxidizing bacteria were responsible for the pH decrease, and
      (2) chemical processes caused complete nitrite oxidation at low pH values. To
      test this hypothesis we set up a mechanistic computer model based on kinetic data
      from literature and we validated the model with additional experiments. The
      simulations fitted the measurements very well. Additionally, an experiment with
      the inhibitor allylthiourea showed that ammonium-oxidizing bacteria were active
      at pH values far below 5.5. Experiments in a sterile reactor confirmed the
      chemical nitrite oxidation to nitrate. Nitrogen balances revealed that 8 +/- 4%
      of the initial nitrogen (ammonium, nitrite, and nitrate) were lost during the
      cycles. On the basis of measurements and simulations we concluded that
      volatilization was responsible for the significant nitrogen loss. We estimated
      that about half of the lost nitrogen volatilized as nitrous acid HNO2. The rest
      mainly volatilized as dinitrogen N2 and nitrous oxide N2O.

PMID- 15984785
TI  - Factors affecting acid neutralizing capacity in the Adirondack region of New
      York: a solute mass balance approach.
AB  - High rates of acidic deposition in the Adirondack region of New York have
      accelerated acidification of soils and surface waters. Annual input-output
      budgets for major solutes and acid-neutralizing capacity (ANC) were estimated for
      43 drainage lake-watersheds in the Adirondacks from 1998 to 2000. Sulfate was the
      predominant anion on an equivalent basis in both precipitation and drainage
      export. Calcium ion had the largest cation drainage export, followed by Mg2+.
      While these watersheds showed net nitrogen (N) retention, the drainage losses of
      SO4(2-), Cl-, base cations, and ANC exceeded their respective inputs from
      precipitation. Land cover (forest type and wetlands) affected the export of SO4(2
      ), N solutes, and dissolved organic carbon (DOC). The relationships of solute
      export with elevation (negative for base cations and Cl-, positive for NO3- and
      H+) suggest the importance of the concomitant changes of biotic and abiotic
      watershed characteristics associated with elevational gradients. The surface
      water ANC increased with the sum of base cations and was greatest in the lakes
      with watersheds characterized by thick deposits of glacial till. The surface
      water ANC was also higher in the lake-watersheds with lower DOC export. Some
      variation in lake ANC was associated with variability in acidic deposition. Using
      a classification system previously developed for Adirondack lakes on the basis
      primarily of surficial geology, lake-watersheds were grouped into five classes.
      The calculated ANC fluxes based on the major sinks and sources of ANC were
      comparable with measured ANC for the thick-till (I) and the medium-till lake
      watersheds with low DOC (II). The calculated ANC was overestimated for the medium
      till with high DOC (III) and the thin-till with high DOC (V) lake-watersheds,
      suggesting the importance of naturally occurring organic acids as an ANC sink,
      which was not included in the calculations. The lower calculated estimates than
      the measured ANC for the thin-till lake-watersheds with low DOC (IV) were
      probably due to the mobilization of Al as an ANC source in these watersheds that
      were highly sensitive to strong acid inputs. Our analysis of various drainage
      lakes across the Adirondacks on the basis of solute mass balances, coupled with
      the use of a lake classification system and GIS data, demonstrates that the lake
      watersheds characterized by shallow deposits of glacial till are highly sensitive
      to acidic deposition not only in the southwestern Adirondack region where
      previous field-based studies were intensively conducted but also across the
      entire Adirondack region. Moreover, the supply of organic acids and Al
      mobilization substantially modify the acid-base status of surface waters.

PMID- 15984786
TI  - Enhanced dechlorination of chlorinated methanes and ethenes by chloride green
      rust in the presence of copper(II).
AB  - The enhanced removal of carbon tetrachloride (CCl4), tetrachloroethene (C2Cl4),
      and trichloroethene (C2HCl3) by chloride green rust (GR(Cl)) in the presence of
      copper ions was investigated. X-ray powder diffraction (XRPD) and X-ray
      photoelectron spectroscopy (XPS) were used to characterize the crystallization
      and chemical speciation, respectively, of the secondary mineral phases produced
      in the GR(Cl)-Cu(II) system. The addition of Cu(II) to GR(Cl) suspensions
      resulted in enhanced dechlorination of the chlorinated hydrocarbons examined in
      this study. The degradation reactions followed pseudo-first-order kinetics and
      the pseudo-first-order rate constant (k(obs)) for CCl4 (20 microM) removal by
      GR(CI) at pH 7.2 was 0.0808 h(-1). Addition of 0.5 mM Cu(II) completely
      dechlorinated CCl4 within 35 min, and the k(obs) was 84 times greater than that
      in the absence of Cu(II). Chloroform (CHCl3), the major chlorinated product in
      CCl4 dechlorination, accumulated at a concentration up to 13 microM in the GR(Cl)
      system alone, but was completely dechlorinated within 9 h in the GR(Cl)-Cu(II)
      suspension. Also, rapid removal of C2Cl4 and C2HCl3 by GR(Cl) was observed when
      Cu(II) was added. The k(obs) values for the removal of chlorinated ethenes were
      4.7-7 times higher than that obtained in the absence of Cu(II). In addition, the
      k(obs) for PCE removal increased linearly with respect to Cu(II) concentrations
      in the range from 0.1 to 1.0 mM. Addition of Cu(II) at a concentration higher
      than 1.0 mM decreased the k(obs) for the removal of both C2Cl4 and C2HCl3 due to
      the decrease in structural Fe(II) concentration in GR(Cl) and the changes in
      redox potentials and pH values. Moreover, the highest removal efficiency and rate
      of C2Cl4 was obtained at near-neutral pH when Cu(II) was added into the GR(Cl)
      suspension. XPS and XRPD results showed that the Fe(II) in the GR(Cl) suspension
      could reduce Cu(II) to both Cu(I) and metallic Cu. These findings are relevant to
      the better understanding of the role of abiotic removal of chlorinated
      hydrocarbons during remediation and/or natural attenuation in iron-reducing
      environments.

PMID- 15984787
TI  - Formation and reaction of hydroxycarbonyls from the reaction of OH radicals with
      1,3-butadiene and isoprene.
AB  - 1,3-Butadiene and isoprene (2-methyl-1,3-butadiene) are emitted into the
      atmosphere in vehicle exhaust and, in the case of isoprene, from vegetation. We
      have investigated the formation and further reaction of products of their
      hydroxyl radical-initiated reactions using atmospheric pressure ionization mass
      spectrometry (API-MS) and solid-phase microextraction fibers precoated with O
      (2,3,4,5,6-pentafluorobenzyl)hydroxylamine for on-fiber derivatization of
      carbonyl compounds, with subsequent analysis by thermal desorption and gas
      chromatography with flame ionization detection (SPME/GC-FID) or MS detection.
      Products attributed as HOCH2CH=CHCHO and HOCH2CH=CHCH2ONO2 (and isomers) from 1,3
      butadiene; HOCD2CD=CDCDO and HOCD2CD=CDCD2ONO2 (and isomers) from 1,3-butadiene
      d6; HOCH2C(CH3)=CHCHO and/or HOCH2CH=C(CH3)CHO, and HOCH2C(CH3)=CHCH2ONO2 (and
      isomers) from isoprene; and HOCD2C(CD3)=CDCDO and/or HOCD2CD=C(CD3)CDO, and
      HOCD2C(CD3)=CDCD2ONO2 (and isomers) from isoprene-d8 were observed as their NO2-
      adducts in the API-MS analyses. The hydroxycarbonyls were observed from SPME/GC
      FID analyses of the 1,3-butadiene and isoprene reactions as their oximes,
      together with acrolein, glycolaldehyde, and glyoxal from the 1,3-butadiene
      reaction. A rate constant for the reaction of OH radicals with 4-hydroxy-2
      butenal of (5.7 +/- 1.4) x 10(-11) cm3 molecule(-1) s(-1) at 298 +/- 2 K was
      derived, and formation yields of acrolein and 4-hydroxy-2-butenal from the 1,3
      butadiene reaction of 58 +/- 10% and 25 (+15/-10)%, respectively, were
      determined. Analogous experiments showed that the two C5-hydroxycarbonyls formed
      from isoprene have rate constants for their reactions with OH radicals of (1.0 +/
      0.3) x 10(-10) cm3 molecule(-1) s(-1) and (4 +/- 2) x 10(-11) cm3 molecule(-1)
      s(-1) and a combined yield of approximately 15%, although isomer-specific
      identification of the hydroxycarbonyls was not achieved.

PMID- 15984788
TI  - Differential potentiometric titration: development of a methodology for
      determining the point of zero charge of metal (hydr)oxides by one titration
      curve.
AB  - A new methodology is presented, called differential potentiometric titration
      (DPT), which allows the determination of the point of zero charge (pzc) of metal
      (hydr)oxides using only one potentiometric curve. By performing extensive
      simulations of potentiometric titrations for various model (hydr)oxides, we found
      that an inflection point in a H+(cons,surf) versus pH potentiometric curve
      (H+(cons,surf): hydrogen ions consumed on the surface of the (hydr)oxide) and a
      peak in the corresponding differential curve, dH+(cons,surf)/dpH versus pH,
      appear at a pH equal to the pzc assumed for a model (hydr)oxide. This
      distinguishable peak appears at the same position irrespective of the surface
      ionization and the interfacial model adopted as well as the assumed ionic
      strength. It was found that the aforementioned peak also appears in the high
      resolution differential potentiometric curves experimentally determined for four
      oxides (SiO2, TiO2, gamma-Al2O3, and MgO) that are widely used in various
      environmental and other technological applications. The application of DPT to the
      above-mentioned oxides provided practically the same pzc values as the
      corresponding ones achieved by using four different techniques as well as the
      corresponding isoelectric point (iep) values determined by microelectrophoresis.
      Differences between the pzc and iep values determined using various techniques in
      the case of MgO were attributed to the increasing dissolution of this oxide as pH
      decreases and the adsorption of cations (Mg2+, Na+) on the MgO/electrolytic
      solution interface.

PMID- 15984789
TI  - Effects of progressive anoxia on the solubility of technetium in sediments.
AB  - Technetium is a significant radioactive contaminant from nuclear fuel cycle
      operations. It is highly mobile in its oxic form (as Tc(VII)O4-) but is scavenged
      to sediments in its reduced forms (predominantly Tc(IV)). Here we examine the
      behavior of Tc at low concentrations and as microbial anoxia develops in sediment
      microcosms. A cascade of stable-element terminal-electron-accepting processes
      developed in microcosms due to indigenous microbial activity. TcO4- removal from
      solution occurred during active microbial Fe(III) reduction, which generated
      Fe(II) in the sediments and was complete before sulfate reduction began.
      Microbial community analysis revealed a similar and complex microbial population
      at all three sample sites. At the intermediate salinity site, PauII, a broad
      range of NO3-, Mn(IV), Fe(III), and SO4(2-) reducers were present in sediments
      including microbes with the potential to reduce Fe(III) to Fe(II), although no
      differences in the microbial population were discerned as anoxia developed. When
      sterilized sediments were incubated with pure cultures of NO3(-)-, Fe(III)-, and
      sulfate-reducing bacteria, TcO4- removal occurred during active Fe(III)
      reduction. X-ray absorption spectroscopy confirmed that TcO4- removal was due to
      reduction to hydrous Tc(IV)O2 in Fe(III)- and sulfate-reducing estuarine
      sediments.

PMID- 15984790
TI  - Neptunium(V) partitioning to uranium(VI) oxide and peroxide solids.
AB  - Metaschoepite, [(UO2)8O2(OH)12] x 10H2O, and metastudtite, UO4 x 4H2O, are
      alteration phases anticipated in a spent nuclear fuel repository following the
      moist oxidation of UO2 on a geologic time scale. Dissolved concentrations and
      hence potential mobility of other radionuclides in the fuel, such as the neptunyl
      cation (NpO2+), will likely be determined by the extent of their partitioning
      into these U(VI) solids. 237Np is of particular interest due to its potential
      high mobility and long half-life (2.1 x 10(6) years.) In this study,
      metaschoepite has been precipitated and subsequently transformed to studtite in
      the presence of dissolved Np. The metaschoepite and studtite solids that formed
      initially contained <10 and 6500 ppm Np, respectively. Batch dissolution studies
      of these solids at pH 6 demonstrate release of Np that exceeds congruent
      dissolution of U from metastudtite; furthermore, the released Np cation remains
      in solution. Thus, although the Np partitions into the metastudtite solid
      initially, it is released to solution over time, indicating that metastudtite is
      not likely to serve as a host solid for Np incorporation or sorption of the
      neptunyl cation on long time scales.

PMID- 15984792
TI  - Lake restoration by dosing aluminum relative to mobile phosphorus in the
      sediment.
AB  - In the sediment of the shallow, hypertrophic Lake Sonderby, Denmark, potentially
      mobile phosphorus (Pmobile) was determined by a sequential extraction technique
      as the sum of porewater P, iron-bound P, and nonreactive P (i.e., polyphosphates
      and organic P). A good agreement was observed between loss rates of Pmobile in
      the top 10 cm of the sediment from winter to summer, P release rates measured in
      undisturbed sediment cores, and rates of P accumulation in the lake water from
      winter to summer (22, 32, and 30 mg of P m(-2) day(-1), respectively). This
      suggests that the operationally defined Pmobile was the sediment P fraction
      responsible for the internal loading in the lake. In autumn 2001, 11 mg of
      aluminum (Al) L(-1), equivalent to 31 g of Al m(-2), was added to the lake water.
      This dosage represented a 4:1 molar ratio between Al and Pmobile. The Al
      treatment significantly decreased lake water P, and P precipitated from the lake
      water was recovered as Al-bound P in the sediment after the treatment. Internal P
      loading was reduced by 93% in the two posttreatment years, relative to 2001.
      Accordingly, average summer concentrations of total P in lake water declined from
      1.28 (SE = 0.17) and 1.3 (SE = 0.14) mg L(-1) in the two pretreatment years to
      0.09 (SE = 0.01) and 0.13 (SE = 0.01) mg L(-1) in the posttreatment years. pH
      levels remained unchanged relative to pretreatment levels, while the total
      alkalinity was reduced from 3.2 (SE = 0.04) to 2.7 (SE = 0.03) mequiv L(-1).

PMID- 15984791
TI  - Influence of sediment bioreduction and reoxidation on uranium sorption.
AB  - The influence of sediment bioreduction and reoxidation on U(VI) sorption was
      studied using Fe(II) oxide-containing saprolite from the U.S. Department of
      Energy (DOE) Oak Ridge site. Bioreduced sediments were generated by anoxic
      incubation with a metal-reducing bacterium, Shewanella putrefaciens strain CN32,
      supplied with lactate as an electron donor. The reduced sediments were
      subsequently reoxidized by air contact. U(VI) sorption was studied in NaNO3-HCO3
      electrolytes that were both closed and open to atmosphere and where pH, U(VI),
      and carbonate concentration were varied. Mossbauer spectroscopy and chemical
      analyses showed that 50% of the Fe(III)-oxides were reduced to Fe(II) that was
      sorbed to the sediment during incubation with CN32. However, this reduction and
      subsequent reoxidation of the sorbed Fe(II) had negligible influence on the rate
      and extent of U sorption or the extractability of sorbed U by 0.2 mol/L NaHCO3.
      Various results indicated that U(VI) surface complexation was the primary process
      responsible for uranyl sorption by the bioreduced and reoxidized sediments. A two
      site, nonelectrostatic surface complexation model best described U(VI) adsorption
      under variable pH, carbonate, and U(VI) conditions. A ferrihydrite-based diffuse
      double layer model provided a better estimation of U(VI) adsorption without
      parameter adjustment than did a goethite-based model, even though a majority of
      the Fe(III)-oxides in the sediments were goethite. Our results highlight the
      complexity of the coupled U-Fe redox system and show that sorbed Fe(II) is not a
      universal reductant for U(VI) as commonly assumed.

PMID- 15984793
TI  - Modeling photoinduced algal toxicity of polycyclic aromatic hydrocarbons.
AB  - The influence of light conditions on the toxicity of polycyclic aromatic
      hydrocarbons (PAHs) to different organisms has long been recognized. The aim of
      this study was to investigate whether previously proposed models can be used to
      qualitatively and quantitatively predict photoinduced toxicity to the green algae
      Scenedesmus vacuolatus. For this purpose 14 different PAH compounds were tested
      under three different light conditions for their effects on the algae
      reproduction. Illumination conditions comprised standard algae growth light,
      simulated sunlight aiming to mimic environmental light conditions, and UV
      filtered light in order to minimize light influence on PAH toxicity. Models
      proposed for the prediction of photoinduced toxicity were modified in order to
      account for different exposure conditions and toxic endpoints used in the
      bioassay. The results of this study show that the gap between the highest
      occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital
      (LUMO) proposed as an indication for photoinduced toxicity to Daphnia magna can
      be used as a qualitative indication of a potential photoinduced toxicity to the
      green algae Scenedesmus vacuolatus. The impact of light conditions on PAH
      toxicity can be quantified by a linear model which allows the estimation of the
      ED50 of each compound from the amount of absorbed photons and an empirically
      determined relative phototoxic efficacy value of the compound.

PMID- 15984794
TI  - Evidence for the Stepwise Stress Model: Gambusia holbrooki and Daphnia magna
      under acid mine drainage and acidified reference water stress.
AB  - The Stepwise Stress Model (SSM) states that a cascade of regulative behavioral
      responses with different intrinsic sensitivities and threshold values offers
      increased behavioral plasticity and thus a wider range of tolerance for
      environmental changes or pollutant exposures. We tested the SSM with a widely
      introduced fish Gambusia holbrooki (Girard) (Pisces, Poeciliidae) and the
      standard laboratory test species Daphnia magna Straus (Crustacea, Daphniidae).
      The stress was simulated by short-term exposure to acid mine drainage (AMD) and
      to acidified reference water (ACID). Recording of behavioral responses with the
      multispecies freshwater biomonitor (MFB) generated continuous time-dependent dose
      response data that were modeled in three-dimensional (3D) surface plots. Both the
      pH-dependent mortalities and the strong linear correlations between pH and
      aqueous metals confirmed the toxicity of the AMD and ACID gradients,
      respectively, for fish and Daphnia, the latter being more sensitive. AMD stress
      at pH < or = 5.5 amplified circadian rhythmicity in both species, while ACID
      stress did so only in G. holbrooki. A behavioral stepwise stress response was
      found in both species: D. magna decreased locomotion and ventilation (first step)
      (AMD, ACID), followed by increased ventilation (second step) (AMD). G. holbrooki
      decreased locomotion (first step) (AMD, ACID) and increased ventilation at
      intermediate pH levels (second step) (AMD). Both species, although from different
      taxonomic groups and feeding habits, followed the SSM, which might be expanded to
      a general concept for describing the behavioral responses of aquatic organims to
      pollution. Stepwise stress responses might be applied in online biomonitors to
      provide more sensitive and graduated alarm settings, hence optimizing the "early
      warning" detection of pollution waves.

PMID- 15984795
TI  - Representation of secondary organic aerosol laboratory chamber data for the
      interpretation of mechanisms of particle growth.
AB  - Absorptive models of gas-particle partitioning have been shown to be successful
      in describing the formation and growth of secondary organic aerosol (SOA). Here
      the expression for particle growth derived by Odum et al. (Odum, J. R.; Hoffmann,
      T.; Bowman, F.; Collins, D.; Flagan, R. C.; Seinfeld, J. H. Gas/particle
      partitioning and secondary organic aerosol yields. Environ. Sci. Technol. 1996,
      30, 2580-2585) is extended to facilitate interpretation of SOA growth data
      measured in the laboratory in terms of the underlying chemistry, even when
      details of the reactions are not well-constrained. A simple (one-component)
      expression for aerosol growth (deltaM) as a function of the amount of hydrocarbon
      reacted (deltaHC) is derived, and the effects of changes to three key parameters,
      stoichiometric yield of condensable species, gas-particle partitioning
      coefficient, and concentration of preexisting aerosol, are discussed. Two sets of
      laboratory chamber data on SOA growth are examined in this context: the
      ozonolysis of alpha-pinene and the OH-initiated photooxidation of aromatic
      compounds. Even though these two systems have a number of significant
      differences, both are described well within this framework. From the shapes of
      the deltaM versus deltaHC curves in each case, the importance of poorly
      constrained chemistry such as heterogeneous reactions and gas-phase reactions of
      oxidation products is examined.

PMID- 15984796
TI  - Effect of lot variability on ultraviolet radiation inactivation kinetics of
      Cryptosporidium parvum oocysts.
AB  - Numerous studies have demonstrated the efficiency of ultraviolet (UV) radiation
      for the inactivation of oocysts of Cryptosporidium parvum. In these studies
      inactivation is measured as reduction in oocysts. A primary goal is to estimate
      the UV radiation required to achieve a high degree of inactivation. Different
      lots of Cryptosporidium parvum oocysts are used in these studies, and the
      inactivation rate may vary depending on the lot of oocysts used. The goal of this
      paper is to account for the error in estimating the amount of inactivation after
      exposure to UV radiation, and for the effect of lot variability in determining
      the required UV radiation. A Bayesian approach is used to simultaneously model
      the logistic dose-response model and the UV inactivation kinetic model. The
      oocysts lot variability is incorporated using a hierarchical Bayesian model.
      Posterior distributions using Markov Chain Monte Carlo method is used to obtain
      estimates and Bayesian credible interval for the required UV radiation to achieve
      a given inactivation level of Cryptosporidium parvum oocysts.

PMID- 15984797
TI  - Spatial variability of fine particle mass, components, and source contributions
      during the regional air pollution study in St. Louis.
AB  - Community time-series epidemiology typically uses either 24-hour integrated
      particulate matter (PM) concentrations averaged across several monitors in a city
      or data obtained at a central monitoring site to relate PM concentrations to
      human health effects. If the day-to-day variations in 24-hour integrated
      concentrations differ substantially across an urban area (i.e., daily
      measurements at monitors at different locations are not highly correlated), then
      there is a significant potential for exposure misclassification in community time
      series epidemiology. If the annual average concentration differs across an urban
      area, then there is a potential for exposure misclassification in epidemiologic
      studies that use annual averages (or multi-year averages) as an index of exposure
      across different cities. The spatial variability in PM2.5 (particulate matter <
      or = 2.5 microm in aerodynamic diameter), its elemental components, and the
      contributions from each source category at 10 monitoring sites in St. Louis,
      Missouri were characterized using the ambient PM2.5 compositional data set of the
      Regional Air Pollution Study (RAPS) based on the Regional Air Monitoring System
      (RAMS) conducted between 1975 and 1977. Positive matrix factorization (PMF) was
      applied to each ambient PM2.5 compositional data set to estimate the
      contributions from the source categories. The spatial distributions of components
      and source contributions to PM2.5 at the 10 sites were characterized using
      Pearson correlation coefficients and coefficients of divergence. Sulfur and PM2.5
      are highly correlated elements between all of the site pairs Although the
      secondary sulfate is the most highly correlated and shows the smallest spatial
      variability, there is a factor of 1.7 difference in secondary sulfate
      contributions between the highest and lowest site on average. Motor vehicles
      represent the next most highly correlated source component. However, there is a
      factor of 3.6 difference in motor vehicle contributions between the highest and
      lowest sites. The contributions from point source categories are much more
      variable. For example, the contributions from incinerators show a difference of a
      factor of 12.5 between the sites with the lowest and highest contributions. This
      study demonstrates that the spatial distributions of elemental components of
      PM2.5 and contributions from source categories can be highly heterogeneous within
      a given airshed and thus, there is the potential for exposure misclassification
      when a limited number of ambient PM monitors are used to represent population
      average ambient exposures.

PMID- 15984798
TI  - Model demonstrating the potential for coupled nitrification denitrification in
      soil aggregates.
AB  - A model of reactive, multi-species diffusion has been developed to describe N
      transformations in spherical soil aggregates, emphasizing the effects of
      irrigation with reclaimed wastewater. Oxygen demand for respiratory activity has
      been shown to promote the establishment of anaerobic conditions. Aggregate size
      and soil respiration rate were identified as the most significant parameters
      governing the existence and extent of the anaerobic volume in aggregates. The
      inclusion of kinetic models describing mineralization, nitrification, and
      denitrification facilitated the investigation of coupled
      nitrification/denitrification (CND), subject to O2 availability. N
      transformations are shown to be affected by effluent-borne NH4+-N content, in
      addition to elevated BOD and pH levels. Their incremental contribution to O2
      availability has been found to be secondary to respiratory activity. At the
      aggregate level, significant differences between apparent and gross rates of N
      transformations were predicted (e.g., NH4+ oxidation and N2 formation), resulting
      from diffusive constraints due to aggregate size. With increasing anaerobic
      volume, the effective nitrification rate determined at the aggregates level
      decreases until its contribution to nitrification is negligible. It was found
      that the nitrification process was predominantly limited to aggregates <0.25 cm.
      Assuming that nitrification is the main source for NO3- formation,
      denitrification efficiency is predicted to peak in medium-sized aggregates, where
      aerobic and anaerobic conditions coexist, supporting CND. In effluent-irrigated
      soils, the predicted NO2- formation rate in small aggregates is enhanced when
      compared to freshwater-irrigated soils. The difference vanishes with increasing
      aggregate size as anaerobic NO2- consumption exceeds aerobic NO2- formation due
      to the coupling of nitrification and denitrification.

PMID- 15984799
TI  - Quantification of sequential chlorinated ethene degradation by use of a reactive
      transport model incorporating isotope fractionation.
AB  - Compound-specific isotope analysis (CSIA) enables quantification of
      biodegradation by use of the Rayleigh equation. The Rayleigh equation fails,
      however, to describe the sequential degradation of chlorinated aliphatic
      hydrocarbons (CAHs) involving various intermediates that are controlled by
      simultaneous degradation and production. This paper shows how isotope
      fractionation during sequential degradation can be simulated in a 1D reactive
      transport code (PHREEQC-2). 12C and 13C isotopes of each CAH were simulated as
      separate species, and the ratio of the rate constants of the heavy to light
      isotope equaled the kinetic isotope fractionation factor for each degradation
      step. The developed multistep isotope fractionation reactive transport model (IF
      RTM) adequately simulated reductive dechlorination of tetrachloroethene (PCE) to
      ethene in a microcosm experiment. Transport scenarios were performed to evaluate
      the effect of sorption and of different degradation rate constant ratios among
      CAH species on the downgradient isotope evolution. The power of the model to
      quantify degradation is illustrated for situations where mixed sources degrade
      and for situations where daughter products are removed by oxidative processes.
      Finally, the model was used to interpret the occurrence of reductive
      dechlorination at a field site. The developed methodology can easily be
      incorporated in 3D solute transport models to enable quantification of sequential
      CAH degradation in the field by CSIA.

PMID- 15984800
TI  - Quantification of toxic Microcystis spp. during the 2003 and 2004 blooms in
      western Lake Erie using quantitative real-time PCR.
AB  - In August of 2003 and August of 2004, blooms of potentially toxic cyanobacteria
      Microcystis spp. persisted in western Lake Erie. Samples collected from the bloom
      were analyzed for the cyanobacterial toxin microcystin and the presence of
      Microcystis spp. cells. Estimates of microcystin toxicity exceeding 1 microg L(
      1) (microcystin-LR activity equivalents), the safety limit set by the World
      Health Organization, were found from the samples in both 2003 and 2004. The
      presence of Microcystis spp. in water samples was confirmed through standard
      polymerase chain reaction (PCR) using a combination of four primer sets.
      Quantification of Microcystis was accomplished by a real-time PCR assay utilizing
      specific primer-Taq-man probe sets targeted on a conserved, Microcystis-specific
      16S rDNA fragment and a microcystin toxin synthetase gene mcyD. This approach
      allowed us to specifically study the distribution and abundance of toxic
      Microcystis in the lake in contrast to previous studies that have assessed
      Microcystis populations with less refined methods. On the basis of quantification
      by quantitative real-time PCR analysis, the total abundance of Microcystis cells
      in the bloom area varied from 4 x 10(8) to 2 x 10(3) cells L(-1). The results of
      this study provide novel insight regarding the distribution and abundance of
      Microcystis spp. in the western basin of Lake Erie, a region plagued in recent
      years by large-scale (>20 km2) blooms. Our results suggest that the Maumee River
      and Bay may serve as a source for Microcystis to western and central Lake Erie.

PMID- 15984801
TI  - Congener-specific carbon isotopic analysis of technical PCB and PCN mixtures
      using two-dimensional gas chromatography-isotope ratio mass spectrometry.
AB  - Analysis of stable carbon isotope fractionation is a useful method to study the
      sources and fate of anthropogenic organic contaminants such as polychlorinated
      biphenyls (PCBs) in the environment. To evaluate the utility of carbon isotopes,
      determination of isotopic ratios of 13C/12C in source materials, for example,
      technical PCB preparations, is needed. In this study, we determined delta13C
      values of 31 chlorobiphenyl (CB) congeners in 18 technical PCB preparations and
      15 chloronaphthalene (CN) congeners in 6 polychlorinated naphthalene preparations
      using two-dimensional gas chromatography-combustion furnace-isotope ratio mass
      spectrometry (2DGC-C-IRMS). Development of 2DGC-IRMS enabled improved resolution
      and sensitivity of compound-specific carbon isotope analysis (CSIA) of CB or CN
      congeners. Delta13C values of PCB congeners ranged from -34.4 (Delors) to 
      22.0/1000 (Sovol). Analogous PCB preparations with similar chlorine content, but
      different geographical origin, had different delta13C values. PCB preparations
      from Eastern European countries--Delors, Sovol, Trichlorodiphenyl, and Chlorofen-
      had distinct delta13C values. PCB mixtures showed increased 13C depletion with
      increasing chlorine content. Delta13C values for individual CB congeners varied
      depending on the degree of chlorination in technical mixtures. Delta13C values of
      CN congeners in Halowaxes ranged from -26.3 to -21.7/1000 and these values are
      within the ranges observed for PCBs. This study establishes the range of delta13C
      values in technical PCB and PCN preparations, which may prove to be useful in the
      determination of sources of these compounds in the environment. This is the first
      study to employ 2DGC-IRMS analysis of delta13C values in technical PCB and PCN
      preparations.

PMID- 15984802
TI  - High time resolution and size-segregated analysis of aerosol bound polycyclic
      aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are an ubiquitous class of compounds in
      the environment, mostly generated by anthropogenic processes. High time
      resolution measurements are necessary to gain further knowledge on the fate and
      diurnal pattern of these often carcinogenic and mutagenic compounds in the
      atmosphere. It is expected to find a strong correlation of the PAH levels with
      the strength and proximity to sources, as well as with meteorological parameters.
      To determine the fate of particle-bound PAHs, they were sampled in this study at
      an urban background site in Zurich, Switzerland, during summer 2002 and winter
      2003. Particle-bound PAHs were collected with a rotating drum impactor and
      subsequently analyzed with two-step laser mass spectrometry. Using this
      combination of sampling and measurement, size-segregated (10-1.1, 1.1-0.3, and
      0.3-0.1 microm) and high time resolution (20 min) data were obtained. The
      pronounced diurnal cycle (with day/night ratios of 0.1) was only altered during
      intensive atmospheric mixing periods (resulting in day/night ratios of up to 8)
      by cleaner air from upper atmospheric layers which was mixed into the boundary
      layer. During summer, signal intensities due to particle-bound PAHs were about a
      factor of 2-10 lower than during winter.

PMID- 15984803
TI  - Sediment dilution method to determine sorption coefficients of hydrophobic
      organic chemicals.
AB  - Sorption coefficients of hydrophobic organic chemicals (HOC) to sediments and
      soils can easily be underestimated in traditional batch experiments, especially
      because analysis of the aqueous concentration often includes compounds sorbed to
      colloidal organic matter. In this work, a "sediment dilution approach" has been
      combined with measurements of freely dissolved concentrations to determine
      sorption coefficients of five chlorobenzenes and two chloroanilines in spiked
      sediment and of two unknown chemicals in field-contaminated sediment. A range of
      sediment suspensions with different sediment-water ratios was made. Freely
      dissolved concentrations in these suspensions were measured by negligible
      depletion solid-phase microextraction (nd-SPME). Sediment-water sorption
      coefficients (KD) were derived from the decrease of the freely dissolved
      concentrations as a function of the "dilution factor" (DF = volume water/mass
      sediment). The determined sorption coefficients were very similar to literature
      values. The experimental setup provides sorption coefficients without the need
      for total extractions, and the negligible depletion SPME technique does not
      require phase separation. The proposed method might be an alternative for batch
      equilibrium experiments to determine sorption coefficients.

PMID- 15984804
TI  - Shifts in relative tissue delta15N values in snowy egret nestlings with dietary
      mercury exposure: a marker for increased protein degradation.
AB  - Shifts in tissue nitrogen isotope composition may be a more sensitive general
      indicator of stress than measurement of high-turnover defensive biomolecules such
      as metallothionein and glutathione. As a physical resource transmitted along the
      trophic web, perturbations in protein nitrogen metabolism may also help resolve
      issues concerning the effects of contaminants on organisms and their
      consequential hierarchical linkages in ecotoxicology. Snowy egret nestlings
      (Egretta thula) fed mercury-contaminated diets of constant nitrogen isotope
      composition exhibited increased relative delta15N values in whole liver (p =
      0.0011) and the acid-soluble fraction (ASF) of the liver (p = 0.0005) when
      compared to nestlings fed a reference diet. When nitrogen isotope data were
      adjusted for the source term of the diet, liver mercury concentrations
      corresponded with both whole liver relative 15N enrichment (r2 = 0.79, slope
      0.009, p < 0.0001) and relative 15N enrichment in the acid-soluble fraction of
      the liver (r2 = 0.85, slope 0.026, p < 0.0001). Meanwhile, significant
      differences were not observed in hepatic levels of the metal-binding peptides
      metallothionein and glutathione despite a nearly 3-fold difference in liver
      mercury content. Because increases in tissue delta15N values result from
      increased rates of protein breakdown relative to synthesis, we propose that the
      increased relative liver delta15N values reflect a shift in protein metabolism.
      The relationship between ASF and mercury was significantly stronger (p < 0.0001)
      than that for whole liver, suggesting that the relationship is driven by an
      increase in bodily derived amino acids in the acid-soluble, free amino acid pool.

PMID- 15984805
TI  - Analyte peptidomimetics selected from phage display peptide libraries: a
      systematic strategy for the development of environmental immunoassays.
AB  - Due to their simplicity, speed, low cost, and specificity, immunoassays have
      become a useful tool for the analysis of environmental pollutants. Once the anti
      hapten antibodies are produced, the same hapten or a related molecule is
      conjugated to a tracer enzyme or coating protein to set up the assay. Here we
      report the use of peptides that mimic the analyte as advantageous substitutes of
      competing haptens. These peptides, which open opportunities for innovation in the
      development of tracer reagents, can be selected from phage display libraries in a
      straightforward systematic manner. The concept was proven using assays for the
      herbicides molinate and atrazine as model systems. Several characteristics of the
      selection process that may affect the final assay were analyzed, such as the
      phage coat proteins fused to the peptide, the use of linear or constrained
      peptide libraries, the effect of the concentration of analyte used during the
      selection process, and the use of monoclonal or polyclonal antibodies as selector
      molecules. In all cases we found that the selected peptides performed with
      improved sensitivity as compared with the chemical hapten conventional assays,
      showing an analogous cross-reactivity pattern. Interestingly, the phage particles
      perform as robust and highly standardized assay reagents, and due to their
      filamentous repetitive structure, they function as sensitive multienzymatic
      reporters.

PMID- 15984806
TI  - Photocatalytic reduction and recovery of mercury by polyoxometalates.
AB  - Photocatalytic reduction of mercury in aqueous solutions using PW12O40(3-) or
      SiW12O40(4-) as photocatalysts has been studied as a function of irradiation
      time, concentration of Hg(II), polyoxometalate, and organic substrate in the
      presence or absence of dioxygen. The photocatalytic cycle starts with irradiation
      of polyoxometalate, goes through the oxidation of, for instance, propan-2-ol
      (used as sacrificial reagent), and closes with the reoxidation of reduced
      polyoxometalate by Hg2+ ions. Mercury(II) is reduced to mercury(I) and finally to
      Hg(0) giving a dark-gray deposit, following a staged one-by-one electron process
      and a first-order kinetics in [Hg2+]. The process is slightly more efficient in
      the absence of dioxygen, while the increase of either catalyst or propan-2-ol
      concentration results in the augmentation of the rate of reduction till a certain
      point where it reaches a plateau. The results show that this method is suitable
      for a great range of mercury concentration from 20 to 800 ppm achieving almost
      complete recovery of mercury up to nondetected traces (<50 ppb). In addition,
      this homogeneous process demonstrates advantages such as the lack of necessity
      for separation of the zero state metal from the catalyst and ensures that the
      precipitation of metal will not poison the catalyst or hinder its photocatalytic
      activity.

PMID- 15984807
TI  - Structure characterization and adsorption properties of pyrolyzed sewage sludge.
AB  - Sewage sludges produced from wastewater treatment plants continue to set
      environmental problems in terms of volume and way of reuse. Thermal treatment of
      sewage sludge is considered as an attractive method in reducing sludge volume,
      and at the same time, it produces reusable byproducts. This paper deals with
      porous carbonaceous materials production from sewage sludge by pyrolysis (or
      carbonization) process with a goal of different industrial applications.
      Carbonization experiments were carried out on two kinds of sludge, namely viscous
      liquid sludge and limed sludge by varying carbonization temperature between 400
      degrees C to 1000 degrees C. The porous structure and surface chemistry of the
      materials obtained were characterized using nitrogen adsorption, scanning
      electron microscopy, elemental analysis, Boehm titration, and pH of zero point of
      charge determination. The results show that basic character of the carbonized
      residues increases with increasing carbonization temperature. Then, carbonization
      allows specific surface area and pore volumes to be developed. Carbonized viscous
      liquid sludge and carbonized limed sludge are mainly mesoporous in nature, with
      specific surface areas reaching about 100 m2 g(-1) and 60 m2 g(-1), respectively.
      Finally, adsorption experiments, in aqueous solution, were carried out and show
      that carbonized viscous liquid sludges and limed sludge remove effectively the
      metallic ion Cu2+, acid and basic dyes, and phenol. Pyrolyzed sludges properties
      seem to be encouraging for the preparation of activated carbon by physical
      activation process.

PMID- 15984808
TI  - Fluctuations of dissolved organic matter in river used for drinking water and
      impacts on conventional treatment plant performance.
AB  - Natural organic matter (NOM) in drinking water supplies can provide precursors
      for disinfectant byproducts, molecules that impact taste and odors, compounds
      that influence the efficacy of treatment, and other compounds that are a source
      of energy and carbon for the regrowth of microorganisms during distribution. NOM,
      measured as dissolved organic carbon (DOC), was monitored daily in the White
      River and the Indiana-American water treatment plant over 22 months. Other
      parameters were either measured daily (UV-absorbance, alkalinity, color,
      temperature) or continuously (turbidity, pH, and discharge) and used with
      stepwise linear regressions to predict DOC concentrations. The predictive models
      were validated with monthly samples of the river water and treatment plant
      effluent taken over a 2-year period after the daily monitoring had ended.
      Biodegradable DOC (BDOC) concentrations were measured in the river water and
      plant effluent twice monthly for 18 months. The BDOC measurements, along with
      measurements of humic and carbohydrate constituents within the DOC and BDOC
      pools, revealed that carbohydrates were the organic fraction with the highest
      percent removal during treatment, followed by BDOC, humic substances, and
      refractory DOC.

PMID- 15984809
TI  - Combustion properties and desulfurization of high sulfur containing Indian and
      Nepali coals using lime-based products.
AB  - Many brick industries and industrial boilers in South Asia use high sulfur
      containing coal as the major fuel. The combustion of these coals leads to serious
      environmental pollution and health problems. The SO2 emissions from the
      combustion of coal can be captured by adding lime-based desulfurizing agents
      (DSA) to the coal briquettes. The physical and combustion characteristics of some
      Indian (Bihar, Assam) and Nepali (Dang, Abidhara, Lignite) coal have been
      studied. The process of desulfurization of these coals was investigated using
      calcium hydroxide and calcium carbonate as DSA. Calcium carbonate is more
      efficient in char combustion than volatile combustion, whereas calcium hydroxide
      and sodium hydroxides are efficient as DSA in both char and volatile combustion.
      For most of the coals the desulfurization efficiencies are over 80% in case of
      Ca(OH)2 and NaOH for molar ratios of DSA to sulfur (Ca/S) of 2 and 3. For the
      same Ca/S ratios the desulfurization efficiency is about 75% when calcium
      carbonate is used. Use of calcium carbonate and calcium hydroxide as DSA in coal
      briquettes could be an efficient and economical way to control the pollution from
      the use of high sulfur containing coals used in brick industries in Nepal and
      South Asia.

PMID- 15984810
TI  - Microbial passage in low pressure membrane elements with compromised integrity.
AB  - The main objective of this study was to evaluate microbial passage through
      membrane elements with various levels of compromised integrity while installed
      within full-scale UF/MF systems. Challenge tests were performed for this purpose
      with the microbial contaminant surrogates Bacillus subtilis spores at two
      drinking water treatment plants. The experimental units used were one of several
      parallel racks part of each plant in which one of the elements was installed with
      various levels of compromised integrity achieved by precutting several hollow
      fibers and inserting removable pin-plugs atthe corresponding ends of the broken
      fiber segments. The UF rack was operated with 38 elements online (the rack has 50
      elements) and was designed for an inside-out operation, and the MF rack included
      50 elements and was operated in an outside-in mode (with a permeate outlet at one
      fiber end only). Spore removals observed for both the UF and MF racks with all
      precut fibers plugged were equal to or greater than 99.9992%, and as expected the
      removal efficiency deteriorated with an increasing number of unplugged fibers.
      Predictions made with a model based on the use of the Hagen-Poisseuille equation
      for laminar flow and the Darcy-Weisbach expression for turbulent flow inside
      broken fibers were found to provide an adequate conservative representation of
      experimental results. Additional simulations performed with the verified model
      revealed the occurrence of a greater microbial passage for an inside-out
      configuration compared to an outside-in mode. A lower microbial passage was
      predicted for the outside-in element configuration with one permeate outlet as
      compared to an element with permeate outlets at both fiber ends. The model offers
      a useful tool that together with other considerations such as membrane fouling,
      cleaning, and durability would assist in the selection of low-pressure membrane
      element configuration.

PMID- 15984811
TI  - Physicochemical properties related to long-term phosphorus retention by drinking
      water treatment residuals.
AB  - Drinking-water treatment residuals (WTRs) are nonhazardous materials that can be
      obtained free-of-charge from drinking-water treatment plants to reduce soluble
      phosphorus (P) concentrations in poorly P sorbing soils. Phosphorus sorption
      capacities of WTRs can vary 1-2 orders of magnitude, on the basis of short-term
      equilibration times (up to 7 d), but studies dealing with long-term (weeks to
      months) P retention by WTRs are lacking. Properties that most affect long-term P
      sorption capacities are pertinent to the efficacy of WTRs as amendments to
      stabilize P in soils. This research addressed the long-term (up to 80 d) P
      sorption/desorption characteristics and kinetics for seven WTRs, including the
      influence of specific surface area (SSA), porosity, and total C content on the
      overall magnitude of P sorption by seven WTRs. The data confirm a strong but
      variable affinity for P by WTRs. Aluminum-based WTRs tended to have higher P
      sorption capacity than Fe-based WTRs. Phosphorus sorption with time was biphasic
      in nature for most samples and best fit to a second-order rate model. The P
      sorption rate dependency was strongly correlated with a hysteretic P desorption,
      consistent with kinetic limitations on P desorption from micropores. Oxalate
      extractable Al + Fe concentrations of the WTRs did not effectively explain long
      term (80 d) P sorption capacities of the WTRs. Micropore (CO2-based) SSAs were
      greater than BET-N2 SSAs for most WTRs, except those with the lowest (<80 g kg(
      1)) total C content. There was a significant negative linear correlation between
      the total C content and the CO2/N2 SSA ratio. The data suggest that C in WTRs
      increases microporosity, but reduces P sorption per unit pore volume or surface
      area. Hence, variability in C content confounds direct relations among SSA,
      porosity, and P sorption. Total C, N2-based SSA, and CO2-based SSAs explained 82%
      of the variability in the long-term P sorption capacities of the WTRs. Prediction
      of long-term P sorption capacities for different WTRs may be achieved by taking
      into account the three proposed variables.

PMID- 15984812
TI  - Oxidation of pharmaceuticals during ozonation of municipal wastewater effluents:
      a pilot study.
AB  - To reduce the release of pharmaceuticals and endocrine disruptors into the
      aquatic environment or to remove them from wastewater intended for direct or
      indirect reuse, the application of advanced wastewater treatment may be required.
      In the present study, municipal wastewater effluents were treated with ozone (O3)
      in a pilot-scale plant consisting of two bubble columns. The investigated
      effluents, which varied in suspended solids concentrations, comprised an effluent
      of conventional activated sludge treatment (CAS), the same effluent dosed with 15
      mg of TSS L(-1) of activated sludge (CAS + SS), and the effluent of a membrane
      bioreactor pilot plant (MBR). Selected classes of pharmaceuticals were spiked in
      the wastewater at realistic levels ranging from 0.5 to 5 microg L(-1). Samples
      taken at the inlet and the outlet of the pilot plant were analyzed with liquid
      chromatography (LC)-electrospray tandem mass spectrometry (MS). Macrolide and
      sulfonamide antibiotics, estrogens, and the acidic pharmaceuticals diclofenac,
      naproxen, and indomethacin were oxidized by more than 90-99% for O3 doses > or =
      2 mg L(-1) in all effluents. X-ray contrast media and a few acidic
      pharmaceuticals were only partly oxidized, but no significant differences were
      observed among the three effluents. These results show that many pharmaceuticals
      present in wastewater can be efficiently oxidized with O3 and that suspended
      solids have only a minor influence on the oxidation efficiency of nonsorbing
      micropollutants.

PMID- 15984813
TI  - Ineffectiveness and poor reliability of arsenic removal plants in West Bengal,
      India.
AB  - In the recent past, arsenic contamination in groundwater has emerged as an
      epidemic in different Asian countries, such as Bangladesh, India, and China.
      Arsenic removal plants (ARP) are one possible option to provide arsenic-safe
      drinking water. This paper evaluates the efficiency of ARP projects in removing
      arsenic and iron from raw groundwater, on the basis of our 2-year-long study
      covering 18 ARPs from 11 manufacturers, both from home and abroad, installed in
      an arsenic affected area of West Bengal, India, known as the Technology Park
      Project (TP project). Immediately after installation of ARPs on August 29, 2001,
      the villagers began using filtered water for drinking and cooking, even though
      our first analysis on September 13, 2001 found that 10 of 13 ARPs failed to
      remove arsenic below the WHO provisional guideline value (10 microg/L), while six
      plants could not achieve the Indian Standard value (50 microg/L). The highest
      concentration of arsenic in filtered water was observed to be 364 microg/L. Our 2
      year study showed that none of the ARPs could maintain arsenic in filtered water
      below the WHO provisional guideline value and only two could meet the Indian
      standard value (50 microg/L) throughout. Standard statistical techniques showed
      that ARPs from the same manufacturers were not equally efficient. Efficiency of
      the ARPs was evaluated on the basis of point and interval estimates of the
      proportion of failure. During the study period almost all the ARPs have undergone
      minor or major modifications to improve their performance, and after our study,
      15 (78%) out of 18 ARPs were no longer in use. In this study, we also analyzed
      urine samples from villagers in the TP project area and found that 82% of the
      samples contained arsenic above the normal limit.

PMID- 15984814
TI  - C60 in water: nanocrystal formation and microbial response.
AB  - Upon contact with water, under a variety of conditions, C60 spontaneously forms a
      stable aggregate with nanoscale dimensions (d = 25-500 nm), termed here "nano
      C60". The color, hydrophobicity, and reactivity of individual C60 are
      substantially altered in this aggregate form. Herein, we provide conclusive lines
      of evidence demonstrating that in solution these aggregates are crystalline in
      order and remain as underivatized C60 throughout the formation/stabilization
      process that can later be chemically reversed. Particle size can be affected by
      formation parameters such as rates and the pH of the water addition. Once formed,
      nano-C60 remains stable in solution at or below ionic strengths of 0.05 I for
      months. In addition to demonstrating aggregate formation and stability over a
      wide range of conditions, results suggest that prokaryotic exposure to nano-C60
      at relatively low concentrations is inhibitory, indicated by lack of growth (> or
      = 0.4 ppm) and decreased aerobic respiration rates (4 ppm). This work
      demonstrates the fact that the environmental fate, distribution, and biological
      risk associated with this important class of engineered nanomaterials will
      require a model that addresses not only the properties of bulk C60 but also that
      of the aggregate form generated in aqueous media.

PMID- 15984815
TI  - Electrochemically assisted microbial production of hydrogen from acetate.
AB  - Hydrogen production via bacterial fermentation is currently limited to a maximum
      of 4 moles of hydrogen per mole of glucose, and under these conditions results in
      a fermentation end product (acetate; 2 mol/mol glucose) that bacteria are unable
      to further convert to hydrogen. It is shown here that this biochemical barrier
      can be circumvented by generating hydrogen gas from acetate using a completely
      anaerobic microbial fuel cell (MFC). By augmenting the electrochemical potential
      achieved by bacteria in this MFC with an additional voltage of 250 mV or more, it
      was possible to produce hydrogen at the cathode directly from the oxidized
      organic matter. More than 90% of the protons and electrons produced by the
      bacteria from the oxidation of acetate were recovered as hydrogen gas, with an
      overall Coulombic efficiency (total recovery of electrons from acetate) of 60
      78%. This is equivalent to an overall yield of 2.9 mol H2/mol acetate (assuming
      78% Coulombic efficiency and 92% recovery of electrons as hydrogen). This bio
      electrochemically assisted microbial system, if combined with hydrogen
      fermentation that produces 2-3 mol H2/mol glucose, has the potential to produce
      ca. 8-9 mol H2/mol glucose at an energy cost equivalent to 1.2 mol H2/mol
      glucose. Production of hydrogen by this anaerobic MFC process is not limited to
      carbohydrates, as in a fermentation process, as any biodegradable dissolved
      organic matter can theoretically be used in this process to generate hydrogen
      from the complete oxidation of organic matter.

PMID- 15984816
TI  - Involvement of constitutive nitric oxide synthase in the portal-systemic
      collaterals of portal hypertensive rats.
AB  - BACKGROUND: Recent studies have shown that endothelial nitric oxide (NO) is
      involved in modulating the vascular response to vasoconstrictors in portal
      systemic collaterals of portal hypertensive rats. This study investigated which
      isoform of NO synthase is involved in the collateral circulation of portal
      hypertensive rats. METHODS: The relaxation response to acetylcholine (10(-8) M,
      10(-7) M and 10(-6) M) in norepinephrine (NE)-preconstricted portal-systemic
      collaterals was investigated after incubation with vehicle (Krebs solution), a
      preferential inducible NO synthase inhibitor (aminoguanidine [AG]), or a non
      selective NO synthase inhibitor (Nomega-nitro-L-arginine [NNA]), in rats with
      partial portal vein ligation. Mean arterial pressure was measured before the
      perfusion experiments. RESULTS: Bodyweight and mean arterial pressure before the
      perfusion studies were similar in the vehicle, AG and NNA groups. Preincubation
      with NNA, but not AG, produced a significant increase in baseline perfusion
      pressure compared with the vehicle group (p < 0.05). The increase in perfusion
      pressure in response to NE was enhanced in the presence of NNA (p < 0.05), but
      not AG. In addition, preincubation with NNA, but not AG, significantly suppressed
      acetylcholine-induced relaxation in the portal-systemic collaterals (p < 0.05).
      CONCLUSION: These results suggest that constitutive, rather than inducible, NO
      synthase is involved in the vascular response to vasoconstrictors in the portal
      systemic collaterals of portal hypertensive rats.

PMID- 15984817
TI  - Tumor necrosis factor-alpha and interleukin-10 in viral and bacterial
      gastroenteritis in children.
AB  - BACKGROUND: Gastroenteritis is a common cause of hospitalization and is
      associated with high morbidity in children. C-reactive protein (CRP), tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) are primary
      mediators of inflammation, and have been implicated in many infectious and non
      infectious inflammatory diseases. The main objective of this study was to
      identify serum markers in viral and bacterial gastroenteritis. METHODS: Thirty
      one patients admitted to a pediatric infection ward with gastroenteritis and
      definite pathogens were enrolled in the study: 17 patients had viral
      gastroenteritis and 14 bacterial gastroenteritis. Serum levels of TNF-alpha, IL
      10 and CRP were measured in these 31 patients, and in a control group of 15
      healthy children. RESULTS: Serum concentrations of TNF-alpha and CRP were
      significantly greater in patients with bacterial gastroenteritis than in patients
      with viral gastroenteritis and healthy controls (p < 0.001). Concentrations of IL
      10 were increased, but not significantly, in patients with viral or bacterial
      gastroenteritis (p = 0.577 vs controls). Regarding diagnosis, the measurement of
      TNF-alpha and CRP levels was 78.6% and 92.0% sensitive, respectively; and 88.2%
      and 58.8% specific, respectively. CONCLUSION: Serum TNF-alpha concentration may
      be a useful marker for distinguishing between viral and bacterial
      gastroenteritis.

PMID- 15984818
TI  - Impact of severe acute respiratory syndrome (SARS) outbreaks on the use of
      emergency department medical resources.
AB  - BACKGROUND: The impact of the severe acute respiratory syndrome (SARS) outbreak
      in 2003 on the emergency department (ED) medical needs of adult patients has not
      been elucidated. The purpose of this study was to investigate the demographic and
      clinical characteristics of ED adult patients before, during and after the SARS
      epidemic in a SARS-dedicated hospital. METHODS: A retrospective, ED chart review
      was conducted, and demographic data were obtained from a computer database, for a
      total of 17,586 patients. Patient information, including age, gender, mode of
      arrival, triage category, time of visit, main diagnosis, use of ED services, and
      status after the ED visit, were collected and compared for pre-, early-, peak-,
      late-, and post-SARS epidemic stages. RESULTS: Demographic data demonstrated a
      significant decrease in patient attendances per day, with a mean reduction of
      92.5 +/- 8.3 patients (43.7 +/- 3.9% reduction in rate; p < 0.01) during peak-
      versus pre-epidemic stages, but revealed no differences in patient age and
      gender. The numbers of patients with ambulance transport, inter-hospital
      referral, and critical illnesses, including DOA, categorized as triage 1, or
      admitted to a ward or intensive care unit after the ED visit, were not influenced
      by the SARS epidemic. The number of patients with upper airway infections and
      suicide attempts from drug overdoses increased, but not statistically
      significantly. The number of patients with other diagnoses decreased
      progressively from early- to peak-epidemic stages, but returned to their earlier
      levels at the post-epidemic stage. Statistically significant decreases (p < 0.05)
      were noted in mean attendance at peak-versus pre- and early-epidemic stages for
      patients with cardiovascular disease, inflammatory or functional bowel disease,
      endocrine disease, dizziness or vertigo, or trauma. CONCLUSION: The SARS outbreak
      did not eliminate the need of critically ill patients for advanced medical
      support. However, besides an overall decrease in patient numbers, the SARS
      epidemic markedly altered demographic information, clinical characteristics, and
      the use of medical services by adult patients in the ED of a SARS-dedicated
      hospital.

PMID- 15984819
TI  - Ophthalmic manifestations of paranasal sinus mucoceles.
AB  - BACKGROUND: Paranasal sinus mucoceles are mucus-containing cysts caused by
      obstruction of the sinus orifice. Although such mucoceles originate in the
      paranasal sinuses, they are usually only associated with ophthalmic and not
      rhinologic symptoms. The purpose of this study was to demonstrate the presence of
      ophthalmic manifestations in patients with paranasal sinus mucoceles, and to
      discuss the possible mechanisms and prognosis for such manifestations. METHODS:
      Medical records for 41 patients with paranasal sinus mucoceles, who presented
      with ophthalmic complaints at our department over a 10-year period (1989-1999),
      were reviewed retrospectively. For analysis of the relationships between
      ophthalmic complaints and the affected paranasal sinuses, we considered the
      paranasal sinuses as anterior and posterior. RESULTS: Proptosis (n = 19),
      periorbital pain (7), and impairment of ocular mobility (5), were common
      manifestations associated with mucoceles in the anterior paranasal sinuses (25
      patients), while blurred vision (n = 9) and impairment of ocular mobility (3)
      were frequently associated with mucoceles in the posterior paranasal sinuses (11
      patients). Ophthalmic complaints resolved in 38 of 41 patients (92.7%) after
      operation. CONCLUSION: The clinical ophthalmic manifestations of paranasal sinus
      mucoceles correlated with the paranasal sinuses involved (i.e. anterior or
      posterior). Because of cranial nerve involvement, mucoceles in the posterior
      paranasal sinuses had a worse prognosis than those in the anterior paranasal
      sinuses.

PMID- 15984820
TI  - Ten-year experience with surgical repair of mycotic aortic aneurysms.
AB  - BACKGROUND: Mycotic aneurysm remains a lethal pathologic entity, especially when
      rupture occurs. It may result from primary aortitis, be induced by septic emboli,
      or be secondary to an adjacent infection, such as pancreatitis or a psoas muscle
      abscess. Surgical intervention is the only way to treat such disease. Even when
      successful repair is achieved by insertion of an interposition in situ graft or
      by performance of an extra-anatomic bypass, the prognosis is poor. The aim of
      this study was to present our experience of managing mycotic aortic aneurysms
      during the past 10 years. METHODS: From January 1994 to June 2004, a total of 734
      patients with aortic aneurysms underwent surgical repair at our institution.
      Among these cases, 17 (2.3%) were shown to be mycotic aneurysms of the ascending
      aorta (n = 1), aortic arch (2), thoracic and thoracoabdominal aorta (3), or
      abdominal aorta (11); 14 patients (mean age, 58.8 years) were male. Preoperative
      imaging studies were performed in all patients. Mycotic aortic aneurysms were
      suspected in 12 of the 17 patients (70.6%) preoperatively, and 4 of these 12
      patients were found to have ruptures on imaging. At the time of surgery, 9 of the
      17 aneurysms (52.9%) were ruptured. Fifteen patients had an interposition graft
      inserted after meticulous debridement, 1 underwent an aorto-aortic bypass, and 1
      underwent an extra-anatomic (axillo-femoral) bypass. An omentum patch was applied
      to wrap the graft in 8 of 11 mycotic aortic aneurysms of the abdominal aorta. The
      most common pathogens were Salmonella spp. (n = 7) and Staphylococcus spp. (4).
      All patients received antibiotic therapy, according to the culture report, for
      about 4-6 weeks postoperatively. RESULTS: In-hospital mortality was 11.8% (n =
      2). Another patient died from massive upper gastrointestinal bleeding 6 months
      after operation because of complications involving an aorto-duodenal fistula, and
      another died from stomach cancer 6 years after surgery. Long-term follow-up
      (mean, 37 months; range, 3-111 months) revealed that, at the time of writing, the
      remaining 13 patients were alive and well, without any recurrence of aneurysm.
      CONCLUSION: Mycotic aneurysm of the aorta is a life-threatening disease,
      especially when rupture occurs. The high mortality rate is due not only to the
      high rupture rate, but also to sepsis. When mycotic aortic aneurysm is diagnosed,
      early surgical intervention is mandatory.

PMID- 15984821
TI  - Urothelial carcinoma of the urinary bladder in young adults--clinical experience
      at Taipei Veterans General Hospital.
AB  - BACKGROUND: The clinical behavior and prognosis of bladder cancer in young
      patients is not well defined. The aim of this study was, therefore, to evaluate
      the clinical behavior, pathologic characteristics and prognosis of urothelial
      carcinoma of the urinary bladder in young adults. METHODS: We retrospectively
      reviewed records from 30 young patients (23 males, 7 females; age < or = 40
      years) with urothelial carcinoma of the urinary bladder who had been treated in
      our hospital between May 1990 and October 2003. Data were analyzed by the Kaplan
      Meier method to assess disease recurrence and survival. RESULTS: The mean age at
      diagnosis was 34.3 +/- 5 years (range, 22-40 years). Fifteen patients presented
      with pTa, 9 with pT1, 4 with pT2, 1 with pT3, and 1 with pT4. Twenty-six patients
      (87.2%) had low-grade bladder cancer, and the other 4 had high-grade disease. The
      most frequent initial presenting symptom was gross hematuria. The mean
      postoperative follow-up period was 72.8 months (range, 4-149 months). Fifty
      percent of superficial bladder cancers recurred a mean of 10.7 months (range, 3
      68 months) after operation. One patient died from invasive bladder cancer after
      radical cystectomy, and 1 died from superficial bladder cancer due to tumor
      progression. The 5-year cancer-specific survival rate was 95.2% for superficial
      cancer and 83.3% for invasive cancer. The overall survival rate was 93.3%.
      CONCLUSION: Urothelial carcinoma of the urinary bladder in young adults is
      usually associated with low grade and low stage. Invasive bladder cancer had no
      worse a survival rate than superficial bladder cancer.

PMID- 15984822
TI  - Chlordiazepoxide-induced Stevens-Johnson syndrome.
AB  - The causes of Stevens-Johnson syndrome (SJS) can be categorized as iatrogenic,
      infectious or idiopathic. Drug-induced SJS is associated with various
      antibiotics, anticonvulsants, and other drugs. However, no previous reports have
      mentioned an association between chlordiazepoxide, a benzodiazepine sedative, and
      SJS. Here, we present a case of SJS induced by chlordiazepoxide overdose. This
      case reminds us that SJS may be an adverse effect of chlordiazepoxide. Further,
      overdosage with benzodiazepine sedatives should be added to the list of potential
      causes of SJS.

PMID- 15984823
TI  - Laryngotracheal involvement as the initial manifestation of relapsing
      polychondritis.
AB  - Relapsing polychondritis (RP) is a rare multisystemic disease characterized by
      recurrent inflammation of cartilaginous and noncartilaginous tissues. When
      laryngotracheal or bronchial cartilages are involved, the disease can be life
      threatening and needs aggressive treatment. Upper airway complaints are rare as
      initial presentations of RP. Here, however, we present a case of RP, with initial
      manifestations of cough and dyspnea that were treated as bronchial asthma for 6
      months. Subglottic stenosis was found in April 2003, during a bronchoscopic
      examination, and emergency tracheostomy was performed. Auricular and nasal
      chondritis and bilateral scleritis developed 3 months after tracheostomy. High
      doses of methylprednisolone and immunosuppressive agents were used, and active
      inflammation in the eyes and ears was controlled, but the patient's upper airway
      was completely collapsed. This case is reported with the hope of increasing
      awareness about the potential for early upper airway involvement in RP.

PMID- 15984824
TI  - Bicycle-handlebar hernia: a rare traumatic abdominal wall hernia.
AB  - Handlebar hernia is a rare, traumatic, abdominal wall hernia caused by high
      velocity direct trauma. It involves disruption of the abdominal wall muscles,
      with bowel loop herniated through the defect in the abdominal wall, and may have
      major or even lethal complications. We report a case of bicycle-handlebar hernia
      in a 9-year-old boy who had all layers of his abdominal wall disrupted by a fall
      when bicycling; however, his skin and intra-abdominal organs were completely
      intact. Computed tomography demonstrated subcutaneous intestinal loops protruding
      through the rent. Primary repair was performed, and his postoperative course was
      uneventful.

PMID- 15984825
TI  - Orbital metastatic osteosarcoma.
AB  - A 15-year-old girl with right tibial osteosarcoma, diagnosed 22 months
      previously, developed right orbital and skull base metastases, with symptoms
      including painful protrusion of the right eyeball and severe visual impairment.
      She underwent embolization of the metastatic tumor, local irradiation, and
      chemotherapy followed by intralesional resection of the mass because extensive
      involvement of the skull base precluded complete surgical resection. The best
      corrected visual acuity in her right eye initially decreased to 20/200, then
      dropped to no light perception after embolization, and then improved to counting
      fingers at 50 cm after radiotherapy. The symptoms of pain and proptosis subsided
      completely. After 24 months of follow-up from the presentation of orbital
      metastasis, the patient's right-eye vision remained unchanged. The surgical
      specimen revealed a necrotic tumor similar to osteosarcoma. In conclusion,
      orbital metastasis of osteosarcoma is rare, but may lead to severe visual
      impairment. Combined radiotherapy, chemotherapy and surgery can partially relieve
      symptoms, but cannot completely eradicate the tumors.

PMID- 15984826
TI  - pi-Conjugated conjoined double helicene via a sequence of three oxidative CC- and
      NN-homocouplings.
AB  - Dimerization of planarized diamine 2 using benzoyl peroxide gave dihydrazine 1 in
      about 70% yield; that is, three dehydrogenations (one CC- and two NN
      homocouplings) and two ring closures were attained in one synthetic step.
      Dihydrazine 1 may be viewed as a chiral pi-conjugated conjoined double helicene,
      with two homochiral [5]helicene-like fragments, annelated in their mid-sections.
      A relatively high barrier of approximately 35 kcal mol-1 for inversion of
      configuration for one of the [5]helicene-like helices in 1 was found.

PMID- 15984827
TI  - Alkaline phosphatase catalysis is ultrasensitive to charge sequestered between
      the active site zinc ions.
AB  - Escherichia coli alkaline phosphatase (AP) is a prototypical bimetalloenzyme,
      facilitating catalysis of phosphate monoester hydrolysis with two Zn2+ metal ions
      that are only 4 A apart. In the reaction's transition state, one of the
      nonbridging oxygen atoms of the transferred group appears to interact directly
      with the Zn2+ ion metallocluster. To determine the importance and the energetic
      properties of this interaction, we systematically varied the charge on this
      oxygen atom, exploiting the ability of AP to catalyze reactions of different
      classes of substrates. We observed that the AP catalytic proficiency correlates
      very well (R2 = 0.98) with the charge on this oxygen atom, over 8 orders of
      magnitude of catalytic proficiency. The slope of this linear correlation (31 +/-
      2 kcal/mol per unit charge) is extraordinarily steep, indicating that AP greatly
      discriminates between differentially charged substrates. We suggest that this
      discrimination arises via an electrostatic interaction with the bimetallocluster.
      The dependence of the AP catalytic proficiency on the nonbridging oxygen charge
      is much larger than charge perturbation effects observed previously for other
      proteins. We propose that AP uses folding energy to position the two Zn2+ metal
      ions in close proximity, thereby creating an active site with a high
      electrostatic potential that is extraordinarily sensitive to the charge that
      "solvates" the metallocluster. The sensitivity of enzyme energetics to systematic
      variation in electrostatic properties provides a powerful measure of the active
      site environment. Future work comparing the sensitivity of related enzymes that
      have been optimized to catalyze different reactions will help reveal how natural
      selection has tuned related active sites to favor different reactions.

PMID- 15984828
TI  - Sugar sensing with synthetic multifunctional pores.
AB  - Recently, synthetic multifunctional pores have been identified as "universal"
      detectors of chemical reactions. In this report, we show that with the assistance
      of enzymes as variable co-sensors, synthetic multifunctional pores can serve as
      similar universal sensors of variable components in mixed analytes. Sugar sensing
      in soft drinks is used to exemplify this new concept. This is achieved using
      invertase and hexokinase as co-sensors and a new synthetic multifunctional pore
      capable of discriminating between ATP and ADP in an "on-off" manner as sensor.
      The on-off discrimination between ATP as good and ADP as poor pore blocker is
      shown to be reasonably tolerant of changing experimental conditions. These
      results identify universal sensing with synthetic multifunctional pores as a
      robust, sensitive, and noninvasive method with appreciable promise for practical
      applications.

PMID- 15984829
TI  - Photochemically and thermally tunable planar defects in colloidal photonic
      crystals.
AB  - We report a bottom-up synthesis of a photochemically and thermally active
      azobenzene-based polyelectrolyte multilayer (PEM) planar defect embedded in a
      colloidal photonic crystal (CPC). Both photoisomerization and thermal cycling
      lead to a precise tuning of an intragap transmitting state induced by the PEM
      structural defect.

PMID- 15984830
TI  - Fluorescent profiling of natural product producers.
AB  - The identification of natural product producer organisms remains a problem for
      both isolation and natural product classification. A concise screen is developed
      through fluorescent modification of a set of natural products that offer a common
      activity. Through real-time multicolor microscopy, the processing, storage, and
      effects of a natural product are rapidly screened at the level of the strain and
      individual organism.

PMID- 15984831
TI  - Platinum stilbazoles: ring-walking coupled with aryl-halide bond activation.
AB  - The reaction between tetrakis(triethylphosphine)platinum(0) and 4-[trans-2-(4
      bromophenyl)vinyl]pyridine (1) is examined. Initially, the metal center
      coordinates to the bridging double bond of 1. Complexes 2 and 3 were fully
      characterized, and their X-ray crystallography structures are presented. Upon
      heating, either in solution or in the solid state, complex 2 undergoes C-Br
      oxidative addition to give complex 3. Kinetic studies revealed that this
      conversion is unimolecular and does not involve dissociation of the metal center
      from the double bond. Density functional studies show that a plausible mechanism
      involves the metal center "walking" around the pi-system from the bridging C=C
      double bond to the C-Br bond.

PMID- 15984832
TI  - Molecules that assemble by sound: an application to the instant gelation of
      stable organic fluids.
AB  - The first molecule that assembles by ultrasound is described. An association
      inert dinuclear Pd complex, anti-1a, which is stabilized by intramolecular pi
      stacking interactions, gelatinizes a variety of organic solvents instantly upon
      brief presonication for a few seconds. This is the first quick, positive, and
      reversible method for the remote switching of stable sol-gel phases. Uniquely,
      the rate can be precisely controlled over the range between "no gelation" and
      "instant gelation" simply by tuning the sonication time.

PMID- 15984833
TI  - Bacterial aerobic synthesis of nanocrystalline magnetite.
AB  - The synthesis of iron oxide nanoparticles of the predominantly magnetite phase by
      the reaction of aqueous iron complexes with the bacterium, Actinobacter spp., is
      described. This reaction occurs at room temperature and under aerobic conditions,
      resulting in the formation of superparamagnetic magnetite.

PMID- 15984834
TI  - Quantum dot-based western blot technology for ultrasensitive detection of tracer
      proteins.
AB  - The present study describes two quantum dot-based Western blotting protocols for
      ultrasensitive detection of "tracer" proteins in cell lysates.

PMID- 15984835
TI  - Remarkably volatile copper(II) complexes of N,N'-unsymmetrically substituted 1,3
      diketimines as precursors for Cu metal deposition via CVD or ALD.
AB  - To enhance the volatility of the copper precursor in the copper deposition
      process, it was envisioned that N,N'-unsymmetrically substituted 1,3-diketimines
      should be more volatile than their symmetrically substituted counterparts. A
      variety of Cu(II) (N,N'-unsymmetrically substituted 1,3-diketiminate) complexes
      have been synthesized and have proven to be much more volatile than their
      symmetrical counterparts. This makes the new materials particularly attractive to
      the ALD and CVD processes. Among the new compounds, 8-a and 8-b are sublimable
      even at room temperature.

PMID- 15984836
TI  - Light-emitting efficiency tuning of rod-shaped pi conjugated systems by donor and
      acceptor groups.
AB  - In view of the increasing importance of highly efficient light-emitting materials
      in chemistry, biological science, and materials science, we investigated the
      light-emitting efficiency tuning of rod-shaped oligo(p-phenylene ethynylene)s
      (OPEs, trimeric to pentameric systems) by donor and acceptor groups, so that they
      emit the very intense fluorescence (Phif approximately 1.0, log epsilon
      approximately 5) at 460 nm as the desired wavelength region. This goal was
      achieved by side modification by MeO (donor) groups and end modification by a CN
      substituted benzene ring or CF3-substituted pyridine ring (acceptor) of
      tetrameric p-phenylene ethynylene rod-shaped molecules (Phif = 0.96, lambdaem =
      458 nm, log epsilon = 4.96 for the former and Phif = 0.99, lambdaem = 459 nm, log
      epsilon = 4.92 for the latter). The high Phif values for 11 and 12 are
      interpreted in terms of kr (radiative rate constant) and kd (radiationless rate
      constant). The linear relationship with a positive slope between Phif and the
      Hammett sigma constant was found for the first time. It is found that kd rather
      than kr varies with sigmap-X. The photophysical properties (Phif, lambdaem,
      lambdaabs, log epsilon) were not so altered with the solvent polarity, which
      could be explained by the dipole moments in the excited and ground states. The
      results would be valuable for the molecular design of highly efficient light
      emitting materials.

PMID- 15984837
TI  - Explicit treatment of spin labels in modeling of distance constraints from
      dipolar EPR and DEER.
AB  - Current SDSL-EPR methods allow measurement of dipolar distances in the 8-70 A
      range; however, the use of extrinsic probes complicates the interpretation of
      these distances in modeling macromolecular structure and conformational changes.
      The data presented here show that interprobe distances correlate only weakly with
      Cbeta-Cbeta distances, especially for distances that are on the order of the spin
      label tether lengths. Explicitly incorporating the spin label into the modeling
      process increases the experiment/model correlation 4-fold and reduces the
      distance error from 6 A to 3 A.

PMID- 15984838
TI  - Probing the breadth of macrolide glycosyltransferases: in vitro remodeling of a
      polyketide antibiotic creates active bacterial uptake and enhances potency.
AB  - The glycan portion of macrolide antibiotics modulates their efficacy. High-level
      expression of three macrolide GTs and kinetic analysis has revealed a highly
      selective synthetic "tool kit" with such plasticity that 12 glycan-modified
      macrolide antibiotics have been readily created. One of these (1-Gal) is enhanced
      over its parent oleandomycin (1) by "glycotargeting", allowing higher uptake
      through active internalization by virtue of the attachment of a glycan (Gal) not
      normally found on 1. Subsequent release of the targeting glycan by endogenous
      galactosidase activity releases 1.

PMID- 15984839
TI  - Alkali metals plus silica gel: powerful reducing agents and convenient hydrogen
      sources.
AB  - Alkali metals absorbed into silica gel yield three stages of unique loose black
      powders (M-SG) that are strong reducing agents. All react nearly quantitatively
      with water to form hydrogen. Liquid Na-K alloys form air-sensitive powders at
      room temperature that can be converted at 150 degrees C to a form that is
      sensitive to moisture but not to dry air. Slowly heating sodium and silica gel to
      400 degrees C yields a third type that can be handled in ambient air with only
      slow degradation by atmospheric moisture. These materials eliminate many hazards
      associated with pure alkali metals and provide easily handled reducing agents and
      hydrogen sources. They could be used in continuous-flow reactors to reduce and
      protonate aromatics, dechlorinate alkyl and aryl halides, and desulfurize various
      compounds.

PMID- 15984840
TI  - Biosynthesis of TDP-l-mycarose: the specificity of a single enzyme governs the
      outcome of the pathway.
AB  - The biosynthetic pathway for l-mycarose, a 2,6-dideoxy-3-methylhexose found in
      the antibiotic tylosin produced by Streptomyces fradiae, has been studied with
      only two genes in the gene cluster, tylK and tylC2, remaining to be
      characterized. To verify the postulated functions of these two genes and to
      establish the sequence of events in the pathway, functional analyses of the
      proteins encoded by tylK and tylC2 were carried out. The results clearly show
      that TylK functions as the 5-epimerase and TylC2 functions as the 4
      ketoreductase. However, both enzymes exhibit relaxed substrate specificity such
      that the production of TDP-l-mycarose as the sole product of the pathway depends
      on the absolute specificity of TylC3, a methyltransferase involved in an early
      step in the pathway. Exploitation of the promiscuous substrate specificity in the
      late steps of the mycarose pathway could produce new analogues of tylosin as well
      as other antibiotics containing this sugar.

PMID- 15984841
TI  - Synthesis of the azaphilones using copper-mediated enantioselective oxidative
      dearomatization.
AB  - An approach to the asymmetric synthesis of the azaphilone natural products is
      reported involving copper-mediated enantioselective oxidative dearomatization of
      o-alkynylbenzaldehydes. The approach was successfully applied to the synthesis of
      (-)-S-15183a and several unnatural azaphilones.

PMID- 15984842
TI  - Synthesis, structure, and spectroscopy of an oxodiiron(II) complex.
AB  - Bridging oxo species are important in the synthetic and biological chemistry of
      iron, and are found with iron oxidation states from +2 to +4. We report the first
      oxodiiron(II) complex that has been crystallographically characterized. It has
      been examined by NMR, IR, and Mossbauer spectroscopies as well as density
      functional calculations.

PMID- 15984843
TI  - An eta(6)-dienyne transition-metal complex.
AB  - The ruthenium complexes, [(eta5-C5R5)Ru(CH3CN)3]PF6 (1-Cp*, R = Me; 1-Cp, R = H),
      underwent reaction with both 1-(2-chloro-1-methylvinyl)-2-pentynyl-(Z)
      cyclopentene (6-Z) and 1-(2-chloro-1-methylvinyl)-2-pentynyl-(E)-cyclopentene (6
      E) to give (eta5-C5R5)Ru[eta6-(5-chloro-4-methyl-6-propylindan)]PF6 (7-Cp*, R =
      Me; 7-Cp, R = H). In a similar fashion, reaction of 1-Cp and 1-Cp* with 1
      isopropenyl-2-pent-1-ynylcyclopentene (8) led to the formation of (eta5
      C5R5)Ru(eta6-4-methyl-6-propylindan)]PF6 (9-Cp*, R = Me; 9-Cp, R = H). The
      reaction of 1-Cp* with 8 at -60 degrees C in CDCl3 solution led to observation of
      the eta6-dienyne complex, (eta5-C5Me5)Ru[eta6-(1-isopropenyl-2-pent-1
      ynylcyclopentene)]PF6 (10), by 1H NMR spectroscopy. Complexes 7-Cp and 10 were
      characterized by X-ray crystallographic analysis.

PMID- 15984844
TI  - High facial diastereoselectivity in intra- and intermolecular reactions of chiral
      benzylic cations.
AB  - Chiral carbenium ions can be attacked by arene nucleophiles with high facial
      diastereoselectivity (dr >/= 94/6). Benzylic cations, such as 2, were generated
      under acidic conditions and reacted with arenes in intra- and intermolecular
      Friedel-Crafts alkylation reaction. The depicted reaction 1 --> 3 represents one
      example for the unprecedented, highly diastereoselective intermolecular Friedel
      Crafts alkylation reactions which were observed in this study.

PMID- 15984846
TI  - Asymmetric [2,3]-sigmatropic rearrangement of allylic ammonium ylides.
AB  - An asymmetric Lewis acid-mediated [2,3]-sigmatropic rearrangement of allylic
      amines has been developed, affording the corresponding homoallylic amines in good
      yield and excellent enantioselectivities. The rearrangement proceeds by
      complexation of the chiral Lewis acid to the amine followed by deprotonation and
      rearrangement.

PMID- 15984845
TI  - A REDOR NMR study of a phosphorylated statherin fragment bound to hydroxyapatite
      crystals.
AB  - Hydroxyapatite (HAP) is the main mineral component of teeth. It is well-known
      that several salivary proteins and peptides bind strongly to HAP to regulate
      crystal growth. Interactions between a peptide derived from the N-terminal
      fragment of the salivary protein statherin and HAP were measured utilizing
      rotational-echo double-resonance (REDOR) nuclear magnetic resonance (NMR). The
      REDOR measurement from the side chain of the salivary peptide to the HAP surface
      is complicated by two effects: a possible additional dipolar coupling to a
      phosphorylated side chain and the potential proximity of phosphorus atoms to each
      other, resulting in a homonuclear dipolar interaction. Both of these effects were
      addressed, and the smallest model applicable to our system includes the nitrogen
      15 (15N) spin in the lysine side chain and two phosphorus-31 (31P) spins, at
      least one of which must be from the surface phosphates of the HAP.

PMID- 15984847
TI  - Spinel ferrite/MnO core/shell nanoparticles: chemical synthesis of all-oxide
      exchange biased architectures.
AB  - In this communication, we report the synthesis and characterization of organic
      capped core/shell CoFe2O4/MnO nanoparticles. Magnetic properties of the
      core/shell nanoparticles were compared to those of individual CoFe2O4 and MnO
      nanoparticles prepared with similar methods. Magnetic measurements revealed that
      the core/shell nanoparticles displayed a shift in the hysteresis loops
      corresponding to exchange biasing exchange fields of about 0.6 kOe, due to the
      ferrimagnetic/antiferromagnetic interface.

PMID- 15984848
TI  - Surfactant headgroup orientation at the air/water interface.
AB  - We have used vibrational sum-frequency spectroscopy to provide the first
      measurement of the spectrum and orientation of the polar headgroup of a charged
      alkyl surfactant at the air/water interface. Sum-frequency spectra of sodium
      dodecyl sulfate (SDS) are used to arrive at all participating elements of the
      second-order susceptibility tensor. We use these chi(2) elements, together with
      calculated values of the hyperpolarizability, to determine the tilt of the S-O
      bond attached to the alkyl chain and the twist of the S-O-C plane. Thus, a full
      characterization of the orientation of the surfactant headgroup has been
      achieved. This is the first demonstration of the feasibility of sum-frequency
      measurements of sulfate modes in the 1100 cm-1 region, opening possibilities for
      future investigations of surfactant behavior in this spectral region at aqueous
      and solid interfaces.

PMID- 15984849
TI  - Mapping polypeptide self-recognition through (1)H off-resonance relaxation.
AB  - 1H NMR relaxation rates provide a readily available and sensitive probe ideally
      suited to investigate the weak (KD approximately micromolar to millimolar range)
      interactions that frequently mediate polypeptide oligomerization in the early
      steps of amyloid fibrillogenesis. However, the measurement of transverse and
      longitudinal 1H relaxation rates is experimentally challenging due to J-transfer
      and selectivity problems in CPMG and inversion-recovery experiments,
      respectively. We show here that these problems are effectively circumvented by
      measuring nonselective off-resonance relaxation rates using an effective field
      tilted by 35.5 degrees . When applied to the Halpha spins of the Abeta (12-28)
      peptide, the proposed experiment provides a residue-resolution self-recognition
      map which is fully consistent with previous independent mutational studies. The
      method is anticipated to be widely applicable not only to the fast growing family
      of amyloidogenic peptides but also to the screening and mapping of protein-ligand
      interactions in general.

PMID- 15984850
TI  - Organocatalytic asymmetric direct alkylation of alpha-diazoester via C-H bond
      cleavage.
AB  - A new variant of phosphoric acid-catalyzed C-C bond forming reaction, direct
      alkylation of alpha-diazoester, via C-H bond cleavage is presented. The resulting
      products, beta-amino-alpha-diazoesters, are highly functionalized and useful
      synthetic precursors for various types of beta-amino acids.

PMID- 15984851
TI  - Synthesis of nitric oxide-releasing gold nanoparticles.
AB  - We report the synthesis of nitric oxide-releasing gold nanoparticles formed by
      place-exchange reaction of hexanethiol monolayer-protected clusters with diamine
      nitric oxide donor precursor molecules, which are subsequently converted to N
      diazeniumdiolate NO donors. The nitric oxide release from the N-diazeniumdiolate
      modified gold nanoparticles is tunable by varying the number and/or the chemical
      structure of the exchanged amine ligands. The size and stability of NO-releasing
      nanoparticles may prove useful for a range of biomedical and pharmaceutical
      applications.

PMID- 15984852
TI  - Living copolymerization of ethylene with styrene catalyzed by
      (cyclopentadienyl)(ketimide)titanium(IV) complex--MAO catalyst system.
AB  - The copolymerization of ethylene with styrene by Cp*TiCl2(N=CtBu2) (Cp* = C5Me5)
      took place in a living manner in the presence of methylaluminoxane (MAO)
      cocatalyst, although the homopolymerization of neither ethylene nor styrene
      proceeded in a living manner. Both the cyclopentadienyl fragment (Cp') and the
      anionic donor ligand (X) in Cp'TiCl2(X) directly affect the copolymerization
      behavior, the catalytic activities, as well as the styrene incorporation; only
      the above set showed a living copolymerization. No styrene repeating units were
      observed in the resultant poly(ethylene-co-styrene)s, suggesting that a certain
      degree of the styrene insertion inhibited the chain transfer in this catalysis.

PMID- 15984853
TI  - Highly diastereoselective hydrostannylation of allyl and homoallyl alcohols with
      dibutyl(trifluoromethanesulfoxy)stannane.
AB  - Dibutyl(trifluoromethanesulfoxy)stannane (Bu2Sn(OTf)H, 1a) was found to be very
      valuable for highly diastereoselective homolytic hydrostannylation of allyl and
      homoallyl alcohols. alpha,beta-Disubstituted allyl alcohols and alpha,gamma
      disubstituted homoallyl alcohols were converted into gamma- and delta-stannylated
      alcohols with high 1,2-syn and 1,3-syn diastereoselectivity, respectively. The
      origin of the stereochemical outcomes can be rationalized by conformational
      fixation of the intermediary beta-stannylalkyl radical by coordination of the
      hydroxy group to the Lewis acidic tin center.

PMID- 15984855
TI  - Thermal isomerizations of 1-(13)c-2,2,3,3-d(4)-cyclopropane to isotopically
      labeled trimethylene diradicals, 1-propylidenes, and propenes.
AB  - The gas-phase thermal isomerizations of 1-13C-2,2,3,3-d4-cyclopropane lead to
      isotopically labeled propenes characteristic of both the traditional reaction
      mechanism involving a trimethylene diradical intermediate and a previously
      predicted, but never observed, path involving rate-limiting conversion of the
      cyclopropane to singlet 1-propylidenes, followed by a [1,2]-deuterium shift. The
      isomerizations give mixtures of both 1-13C-2,3,3,3-d4-propene and 1-13C-1,2,3,3
      d4-propene, products characteristic of the two mechanisms that are clearly
      observable by 13C{1H} NMR spectroscopy.

PMID- 15984854
TI  - Destroying gadofullerene aggregates by salt addition in aqueous solution of
      Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH(2))](10).
AB  - A combined proton relaxivity and dynamic light scattering study has shown that
      aggregates formed in aqueous solution of water-soluble gadofullerenes can be
      disrupted by addition of salts. The salt content of fullerene-based materials
      will strongly influence properties related to aggregation phenomena, therefore,
      their behavior in biological or medical applications. In particular, the
      relaxivity of gadofullerenes decreases dramatically with phosphate addition.
      Moreover, real biological fluids present a rather high salt concentration which
      will have consequences on fullerene aggregation and influence fullerene-based
      drug delivery.

PMID- 15984856
TI  - Structure of multiresponsive "intelligent" core-shell microgels.
AB  - A doubly temperature-sensitive core-shell microgel composed of two temperature
      sensitive polymers with different lower critical solution temperatures (LCSTs) in
      the core and shell has been studied by small-angle neutron scattering (SANS). The
      application of a novel universal form factor model in the analysis of the SANS
      data reveals that the radial density profile at temperatures above the LCSTs of
      both polymers can be well described by a two-box profile with narrow interfaces.
      At temperatures between the LCSTs, the radial density profile reveals that the
      core in the core-shell microgel has larger dimensions than the naked core. Thus
      the swollen shell pulls the core apart. At temperatures below both LCSTs,
      however, the shell restricts the core swelling, and the core is found to be
      smaller than in its native state. This clearly demonstrates the mutual influence
      of core and shell swelling.

PMID- 15984857
TI  - Size-specific catalytic activity of polymer-stabilized gold nanoclusters for
      aerobic alcohol oxidation in water.
AB  - Gold nanoclusters (phi = 1.3 nm) stabilized by poly(N-vinyl-2-pyrrolidone)
      (Au:PVP NCs) readily oxidize benzylic alcohols to the corresponding aldehydes
      and/or carboxylic acids under ambient temperature in water. Kinetic measurement
      revealed that smaller Au:PVP NCs exhibit higher catalytic activity than larger
      (9.5 nm) homologues and, more surprisingly, than Pd:PVP NCs of comparable size
      (1.5 and 2.2 nm). On the basis of the marked difference in the kinetic isotope
      effect and activation energy between Au:PVP and Pd:PVP NCs, a reaction mechanism
      for alcohol oxidation catalyzed by Au:PVP NCs is proposed in which a superoxo
      like molecular oxygen species adsorbed on the surface of the small Au NCs
      abstracts a hydrogen atom from the alkoxide.

PMID- 15984858
TI  - Strong H(2) binding and selective gas adsorption within the microporous
      coordination solid Mg(3)(O(2)C-C(10)H(6)-CO(2))(3).
AB  - The synthesis of Mg3(NDC)3(DEF)4 (NDC = 2,6-naphthalenedicarboxylate, DEF = N,N
      diethylformamide, 1), the first porous metal-organic framework solid
      incorporating Mg2+ ions, is reported. Its structure consists of linear Mg3 units
      linked via NDC bridges to form a three-dimensional framework, featuring one
      dimensional channels filled with DEF molecules. Significantly, its framework is
      fully analogous to that observed within Zn3(NDC)3(CH3OH)2.2DMF.H2O (2),
      demonstrating that Mg2+ ions can directly substitute for the heavier Zn2+ ions.
      Compound 1 is readily desolvated by heating at 190 degrees C to give the
      microporous solid Mg3(NDC)3, exhibiting a BET surface area of 190 m2/g.
      Adsorption isotherms measured at 77 and 87 K indicate high H2 adsorption
      enthalpies in the range 7.0-9.5 kJ/mol, depending on the degree of loading. In
      addition, the material displays selective adsorption of H2 or O2 over N2 or CO,
      suggesting possible applications in gas separation technologies.

PMID- 15984859
TI  - Steric effects in hula-twist photoisomerization. 1,4-dimethyl- and 2,3-dimethyl
      1,4-diphenylbutadienes.
AB  - 1,4-Dimethyl-1,4-diphenylbutadiene was shown to be able to execute regiospecific
      HT-1 photoisomerization around a methyl group when irradiated in a low
      temperature organic glass, albeit at reduced efficiency. 2,3-Dimethyl-1,4
      diphenylbutadiene exhibited a different type of steric effect, causing the E,E
      isomer to undergo regiospecific HT-1 photoisomerization.

PMID- 15984860
TI  - In situ negative patterning of p-silicon via scanning probe lithography in
      HF/EtOH liquid bridges.
AB  - We succeeded in extending local oxidation to in situ negative patterning. HF/EtOH
      was used as both gap-bridging electrolyte and oxyanion source. EtOH and HF were
      found to be able to accelerate the growth of silicon oxide and simultaneously
      etch grown oxide, respectively. These findings are expected to open new
      possibilities in utilizing local oxidation nanolithography in order to directly
      fabricate deeper well structures while at the same time maintaining lateral sizes
      within the nanometer range.

PMID- 15984861
TI  - In vitro selection of aptamers with affinity for neuropeptide Y using capillary
      electrophoresis.
AB  - Capillary electrophoresis-systematic evolution of ligands by exponential
      enrichment (CE-SELEX) was used to select aptamers for neuropeptide Y (NPY). This
      is the first example of a CE-SELEX selection for aptamers that bind a target
      molecule smaller than itself. One of the limitations of CE-SELEX is that the
      aptamer must exhibit a significant mobility shift when it binds the target to
      facilitate fraction collection. Before this study, it was not clear if smaller
      targets would be capable of inducing a large enough shift in mobility for CE
      SELEX to be successful. NPY is a 36-amino acid peptide (MW = 4272 g/mol), much
      smaller than the 80-base ssDNA used in the selection ( approximately 25 kDa). NPY
      binding aptamers with 300-1000 nM dissociation constants were obtained after only
      four rounds of selection. The specificity of the aptamers was tested using human
      pancreatic polypeptide (hPP). hPP is a 36-amino acid peptide with approximately
      50% homology with NPY. Aptamers with up to 42-fold selectivity for NPY over hPP
      were observed.

PMID- 15984862
TI  - Unusual reactivity of tris(pyrazolyl)borate zirconium benzyl complexes.
AB  - The synthesis and reactivity of [Tp*Zr(CH2Ph)2][B(C6F5)4] (2, Tp* = HB(3,5
      Me2pz)3, pz = pyrazolyl) have been explored to probe the possible role of Tp'MR2+
      species in group 4 metal Tp'MCl3/MAO olefin polymerization catalysts (Tp' =
      generic tris(pyrazolyl)borate). The reaction of Tp*Zr(CH2Ph)3 (1) with
      [Ph3C][B(C6F5)4] in CD2Cl2 at -60 degrees C yields 2. 2 rearranges rapidly to
      [{(PhCH2)(H)B(mu-Me2pz)2}Zr(eta2-Me2pz)(CH2Ph)][B(C6F5)4] (3) at 0 degrees C.
      Both 2 and 3 are highly active for ethylene polymerization and alkyne insertion.
      Reaction of 2 with excess 2-butyne yields the double insertion product
      [Tp*Zr(CH2Ph)(CMe=CMeCMe=CMeCH2Ph)][B(C6F5)4] (4). Reaction of 3 with excess 2
      butyne yields [{(PhCH2)(H)B(mu-Me2pz)2}Zr(Cp*)(eta2-Me2pz)][B(C6F5)4] (6, Cp* =
      C5Me5) via three successive 2-butyne insertions, intramolecular insertion, chain
      walking, and beta-Cp* elimination.

PMID- 15984863
TI  - Reversible light and air-driven lithography by singlet oxygen.
AB  - Monolayers and thin films of diphenylanthracene react in the presence of a
      singlet oxygen sensitizer by irradiation on air to the corresponding
      endoperoxides and reconvert to the starting compounds upon heating. This reaction
      has been applied to create 2D fluorescent pattern structures. Motifs which are
      written by this technique can be erased and replaced by new images.

PMID- 15984864
TI  - Promiscuous fatty acyl CoA ligases produce acyl-CoA and acyl-SNAC precursors for
      polyketide biosynthesis.
AB  - The study of bioactive natural products has undergone rapid advancement with the
      cloning and sequencing of large number of gene clusters and the concurrent
      progress to manipulate complex biosynthetic systems in heterologous hosts. The
      genetic reconstitution necessitates that the heterologous hosts possess substrate
      pools that could be coordinately supplied for biosynthesis. Polyketide synthases
      (PKS) utilize acyl-coenzyme A (CoA) precursors and synthesize polyketides by
      repetitive decarboxylative condensations. Here we show that acyl-CoA ligases,
      which belong to a large family of acyl-activating enzymes, possess potential to
      produce varied starter CoA precursors that could be utilized in polyketide
      biosynthesis. Incidentally, such protein domains have been recognized in several
      PKS and nonribosomal peptide synthetase gene clusters. Our studies with
      mycobacterial fatty acyl-CoA ligases (FACLs) show remarkable tolerance to
      activate a variety of fatty acids that contain modifications at alpha, beta,
      omega, and omega-nu positions. This substrate flexibility extends further such
      that these proteins also efficiently utilize N-acetyl cysteamine, the shorter
      acceptor terminal portion of CoASH, to produce acyl-SNACs. We show that the in
      situ generated acyl-CoAs and acyl-SNACs could be channeled to types I and -III
      PKS systems to produce new metabolites. Together, the promiscuous activity of
      FACL and PKSs provides new opportunities to expand the repertoire of natural
      products.

PMID- 15984865
TI  - Competition between receptors in dynamic combinatorial libraries: amplification
      of the fittest?
AB  - Dynamic combinatorial chemistry is a powerful tool for the discovery of strong
      binders (synthetic receptors or ligands) because binding causes a shift in the
      equilibrium of library members toward those that bind well. Ideally, the best
      binders are selectively amplified. However, theoretical studies predict this is
      not always the case. This paper describes the first quantitative experimental
      evidence proving that, under special circumstances, the preferential
      amplification of suboptimal synthetic receptors can indeed occur. Our results
      also demonstrate that reducing the amount of guest in the library can rectify
      such undesirable behavior and ensures selective amplification of the fittest
      receptor.

PMID- 15984866
TI  - Heats of formation of Co(CO)(2)NOPR(3), R = CH(3) and C(2)H(5), and its ionic
      fragments.
AB  - A joint threshold photoelectron photoion coincidence spectrometry (TPEPICO) and
      collision-induced dissociation (CID) study on the thermochemistry of
      Co(CO)(2)NOPR(3), R = CH(3) (Me) and C(2)H(5) (Et), complexes is presented.
      Adiabatic ionization energies of 7.36 +/- 0.04 and 7.24 +/- 0.04 eV,
      respectively, were extracted from scans of the total ion and threshold electron
      signals. In the TPEPICO study, the following 0 K onsets were determined for the
      various fragment ions: CoCONOPMe(3)(+), 8.30 +/- 0.05 eV; CoNOPMe(3)(+), 9.11 +/-
      0.05 eV; CoPMe(3)(+) 10.80 +/- 0.05 eV; CoCONOPEt(3)(+), 8.14 +/- 0.05 eV;
      CoNOPEt(3)(+), 8.92 +/- 0.05 eV; and CoPEt(3)(+), 10.66 +/- 0.05 eV. These onsets
      were combined with the Co(+)-PR(3) (R = CH(3) and C(2)H(5)) bond dissociation
      energies of 2.88 +/- 0.11 and 3.51 +/- 0.17 eV, obtained from the TCID
      experiments, to derive the heats of formation of the neutral and ionic species.
      Thus, the Co(CO)(2)NOPR(3) (R = CH(3) and C(2)H(5)) 0 K heats of formation were
      found to be -350 +/- 13 and -376 +/- 18 kJ x mol(-)(1), respectively. These heats
      of formation were combined with the published heat of formation of Co(CO)(3)NO to
      determine the substitution enthalpies of the carbonyl to phosphine substitution
      reactions. Room-temperature values of the heats of formation are also given using
      the calculated harmonic vibrational frequencies. Analysis of the TCID
      experimental results provides indirectly the adiabatic ionization energies of the
      free phosphine ligands, P(CH(3))(3) and P(C(2)H(5))(3), of 7.83 +/- 0.03 and 7.50
      +/- 0.03 eV, respectively.

PMID- 15984867
TI  - Molecular AND and INHIBIT gates based on control of porphyrin fluorescence by
      photochromes.
AB  - A molecular triad consisting of a porphyrin (P) covalently linked to two
      photochromes-one from the dihydroindolizine family (DHI) and one from the
      dihydropyrene family (DHP)-has been synthesized and found to act as either a
      molecular AND logic gate or an INHIBIT gate, depending on the inputs and initial
      state of the photochromes. The basis of these functions is quenching of porphyrin
      fluorescence (output of the gates) by the photochromes. The spiro form of DHI
      does not quench porphyrin fluorescence, whereas its betaine isomer strongly
      quenches by photoinduced electron transfer. DHP also quenches porphyrin
      fluorescence, but its cyclophanediene isomer does not. The triad has been
      designed using suitable energetics and electronic interactions, so that although
      these quenching phenomena may be observed, independent isomerization of the
      attached photochromes still occurs. This makes it possible to switch porphyrin
      fluorescence on or off by isomerization of the photochromes using various
      combinations of inputs such as UV light, red light, and heat.

PMID- 15984868
TI  - Tandem sequence of cross metathesis--ring-closing metathesis reaction of alkynyl
      silyloxy-tethered enynes.
AB  - A tandem cross metathesis (CM)--ring-closing metathesis (RCM) sequence to form
      cyclic siloxanes is reported. This new enyne metathesis platform expands the
      scope and utility of the regio- and stereoselective cross metathesis reaction
      between silylated alkynes and terminal alkenes. The initial cross metathesis was
      directed to occur on the alkyne by employing sterically hindered mono-, di-, and
      trisubstituted alkenes tethered to the alkyne via silyl ether. The regio- and
      stereoselectivity feature of the initial CM step in this tandem CM-RCM process is
      identical to that of the CM reactions of silylated alkynes and alkenes. This
      tandem sequence provides both synthetically useful silylated 1,3-diene building
      blocks and insights into the reaction mechanism of the enyne metathesis reaction.

PMID- 15984869
TI  - Synthesis and characterization of salts containing the BrO(3)F(2)(-) anion; a
      rare example of a bromine(VII) species.
AB  - The BrO(3)F(2)(-) anion has been prepared by reaction of BrO(3)F with the
      fluoride ion donors KF, RbF, CsF, [N(CH(3))(4)][F], and NOF. The BrO(3)F(2)(-)
      anion is only the fourth Br(VII) species to have been isolated in macroscopic
      quantities, and it is one of only three oxide fluorides that possess D(3)(h)()
      symmetry, the others being XeO(3)F(2) and OsO(3)F(2). The fluoride ion acceptor
      properties of BrO(3)F contrast with those of ClO(3)F, which does not react with
      the strong fluoride ion donor [N(CH(3))(4)][F] to form the analogous ClO(3)F(2)(
      ) salt. The single-crystal X-ray structures of [NO](2)[BrO(3)F(2)][F] and
      [N(CH(3))(4)][BrO(3)F(2)] confirm the D(3)(h)() symmetry of the BrO(3)F(2)(-)
      anion and provide accurate Br-O (1.593(3)-1.610(6) A) and Br-F (1.849(5)-1.827(4)
      A) bond lengths. The salt, [NO](2)[BrO(3)F(2)][F], is fully ordered,
      crystallizing in the monoclinic space group, C2/c, with a = 9.892(3) A, b =
      12.862(4) A, c = 10.141(4) A, beta = 90.75(2) degrees , V = 12460(7) A(3), Z = 4,
      and R(1) = 0.0671 at -173 degrees C, whereas [N(CH(3))(4))][BrO(3)F(2)] exhibits
      a 2-fold disorder of the anion, crystallizing in the tetragonal space group,
      P4/nmm, with a = 8.5718(7) A, c = 5.8117(6) A, V = 427.02(7) A(3), Z = 2, and
      R(1) = 0.0314 at -173 degrees C. The (19)F chemical shift of
      [N(CH(3))(4))][BrO(3)F(2)] in CH(3)CN is 237.0 ppm and is more deshielded than
      those of the previously investigated Br(VII) species, BrO(3)F and BrF(6)(+). The
      vibrational frequencies of the BrO(3)F(2)(-) anion were determined by use of
      Raman and infrared spectroscopy and were assigned with the aid of electronic
      structure calculations and by analogy with the vibrational assignments reported
      for XeO(3)F(2) and OsO(3)F(2). The internal and symmetry force constants of
      BrO(3)F(2)(-) were determined by use of general valence force field and B-matrix
      methods, respectively, and are compared with those of XeO(3)F(2), OsO(3)F(2), and
      the unknown ClO(3)F(2)(-) anion. The instability of ClO(3)F(2)(-) relative to
      BrO(3)F(2)(-) has been investigated by electronic structure calculations and
      rationalized in terms of atomic charges, Mayer bond orders, and Mayer valencies,
      and the enthalpies of fluoride ion attachment to BrO(3)F and ClO(3)F.

PMID- 15984870
TI  - Synergistic dimetallic effects in propargylic substitution reaction catalyzed by
      thiolate-bridged diruthenium complex.
AB  - The origin of unique catalytic activity of a thiolate-bridged diruthenium complex
      in nucleophilic substitution reactions of propargylic alcohols, which features a
      diruthenium-allenylidene complex as a key intermediate, was studied with the aid
      of density functional calculations (B3LYP). Comparison of mono- and diruthenium
      systems has shown that the rigid but reasonably flexible Ru-Ru core structure
      plays a critical role in the catalyst turnover step (i.e., dissociative ligand
      exchange of the product pi-complex with the starting propargyl alcohol that goes
      through a coordinatively unsaturated Ru complex). In the diruthenium system, the
      energy loss due to coordinative unsaturation can be compensated by reinforcement
      of the Ru-Ru bond, while such an effect is unavailable in the monoruthenium
      counterpart. Weaker back-donation ability of the diruthenium complex is also
      advantageous for dissociation of the pi-complex. Thus, ligand exchange takes
      place smoothly in the diruthenium system to regenerate the reactive species,
      while the monoruthenium reaction stops at a dead-end Ru product pi-complex. The
      present studies have also shown the important role of protic molecules (e.g.,
      MeOH) that mediate smooth proton transfer in the propargyl alcohol-allenylidene
      transformation.

PMID- 15984871
TI  - Telomestatin and diseleno sapphyrin bind selectively to two different forms of
      the human telomeric G-quadruplex structure.
AB  - The human telomeric sequence d[T(2)AG(3)](4) has been demonstrated to form
      different types of G-quadruplex structures, depending upon the incubation
      conditions. For example, in sodium (Na(+)), a basket-type G-quadruplex structure
      is formed. In this investigation, using circular dichroism (CD), biosensor
      surface plasmon resonance (SPR), and a polymerase stop assay, we have examined
      how the addition of different G-quadruplex-binding ligands affects the
      conformation of the telomeric G-quadruplex found in solution. The results show
      that while telomestatin binds preferentially to the basket-type G-quadruplex
      structure with a 2:1 stoichiometry, 5,10,15,20-[tetra-(N-methyl-3-pyridyl)]-26-28
      diselena sapphyrin chloride (Se2SAP) binds to a different form with a 1:1
      stoichiometry in potassium (K(+)). CD studies suggest that Se2SAP binds to a
      hybrid G-quadruplex that has strong parallel and antiparallel characteristics,
      suggestive of a structure containing both propeller and lateral, or edgewise,
      loops. Telomestatin is unique in that it can induce the formation of the basket
      type G-quadruplex from a random coil human telomeric oligonucleotide, even in the
      absence of added monovalent cations such as K(+) or Na(+). In contrast, in the
      presence of K(+), Se2SAP was found to convert the preformed basket G-quadruplex
      to the hybrid structure. The significance of these results is that the presence
      of different ligands can determine the type of telomeric G-quadruplex structures
      formed in solution. Thus, the biochemical and biological consequences of binding
      of ligands to G-quadruplex structures found in telomeres and promoter regions of
      certain important oncogenes go beyond mere stabilization of these structures.

PMID- 15984872
TI  - Direct tyrosine oxidation using the MLCT excited states of rhenium polypyridyl
      complexes.
AB  - Rhenium(I) polypyridyl complexes have been designed for the intramolecular
      photogeneration of tyrosyl radical. Tyrosine (Y) and phenylalanine (F) have each
      been separately appended to a conventional Re(I)(bpy)(CO)(3)CN framework via an
      amide linkage to the bipyridine (bpy) ligand. Comparative time-resolved emission
      quenching and transient absorption spectra of Re(bpy-Y)(CO)(3)CN and Re(bpy
      F)(CO)(3)CN show that Y is oxidized only upon its deprotonation at pH 12. In an
      effort to redirect electron transport so that it is more compatible with
      intramolecular Y oxidation, polypyridyl Re(I) complexes have been prepared with
      the amide bond functionality located on a pendant phosphine ligand. A
      [Re(phen)(PP-Bn)(CO)(2)](PF(6)) (PP = bis(diphenylphosphino)ethylene) complex has
      been synthesized and crystallographically characterized. Electrochemistry and
      phosphorescence measurements of this complex indicate a modest excited-state
      potential for tyrosine oxidation, similar to that for the (bpy)Re(I)(CO)(3)CN
      framework. The excited-state oxidation potential can be increased by introducing
      a monodentate phosphine to the Re(I)(NN)(CO)(3)(+) framework (NN = polypyridyl).
      In this case, Y is oxidized at all pHs when appended to the triphenylphosphine
      (P) of [Re(phen)(P-Y)(CO(3))](PF(6)). Analysis of the pH dependence of the rate
      constant for tyrosyl radical generation is consistent with a proton-coupled
      electron transfer (PCET) quenching mechanism.

PMID- 15984873
TI  - Cell-penetrating cis-gamma-amino-l-proline-derived peptides.
AB  - The synthesis of cis-gamma-amino-l-proline oligomers functionalized at the
      proline alpha-amine with several groups that mimic the side chains of natural
      amino acids, including alanine, leucine, and phenylalanine, is herein described.
      These gamma-peptides enter into different cell lines (COS-1 and HeLa) via an
      endocytic mechanism. The ability of these compounds to be taken up into cells was
      studied at 37 degrees C and 4 degrees C by plate fluorimetry, flow cytometry, and
      confocal microscopy. In addition to their capacity for cellular uptake, these
      unnatural short length oligomers offer advantages over the well-known penetrating
      TAT peptide, such as being less toxic than TAT and protease resistance.

PMID- 15984874
TI  - Docking, triggering, and biological activity of dynemicin A in DNA: a
      computational study.
AB  - The triggering and biological activity of the naturally occurring enediyne
      dynemicin A (1) was investigated, both inside and outside the minor groove of the
      duplex 10-mer B-DNA sequence d(CTACTACTGG).d(CCAGTAGTAG), using density
      functional theory (B3LYP with the 3-21G and 6-31G(d) basis set), BD(T)/cc-pVDZ
      (Brueckner doubles with a perturbative treatment of triple excitations), and the
      ONIOM approach. Enediyne 1 is triggered by NADPH in a strongly exothermic
      reaction (-88 kcal/mol), which involves a number of intermediate steps.
      Untriggered 1 has a high barrier for the Bergman cyclization (52 kcal/mol) that
      is lowered after triggering to 16.7 kcal/mol due to an epoxide opening and the
      accompanying strain relief. The Bergman reaction of triggered 1 is slightly
      exothermic by 2.8 kcal/mol. The singlet biradical formed in this reaction is
      kinetically stable (activation enthalpies of 19.5 and 21.8 kcal/mol for retro
      Bergman reactions) and is as reactive as para-benzyne. The activity-relevant
      docking mode is an edge-on insertion into the minor groove, whereas the
      intercalation between base pairs, although leading to larger binding energies,
      excludes a triggering of 1 and the development of its biological activity.
      Therefore, an insertion-intercalation model is developed, which can explain all
      known experimental observations made for 1. On the basis of the insertion
      intercalation model it is explained why large intercalation energies suppress the
      biological activity of dynemicin and why double-strand scission can be achieved
      only in a two-step mechanism that involves two enediyne molecules, explaining
      thus the high ratio of single-strand to double-strand scission observed for 1.

PMID- 15984875
TI  - ENDOR investigation of the liganding environment of mixed-spin ferric cytochrome
      c'.
AB  - The electronic structure of the 5-coordinate quantum-mechanically mixed-spin
      (sextet-quartet) heme center in cytochrome c' was investigated by electron
      nuclear double resonance (ENDOR), a technique not previously applied to this
      mixed-spin system. Cytochrome c' was obtained from overexpressing variants of
      Rhodobacter sphaeroides 2.4.3. ENDOR for this study was done at the g(//) = 2.00
      extremum where single-crystal-like, well-resolved spectra prevail. The heme meso
      protons of cytochrome c' showed a contact interaction that implied spin
      delocalization arising from the heme (d(z)(2)) orbital enhanced by iron out-of
      planarity. An exchangeable proton ENDOR feature appeared from the proximal His123
      Ndelta hydrogen. This Ndelta hydrogen, which crystallographically has no hydrogen
      bonding partner and thus belongs to a neutral imidazole, showed a larger
      hyperfine coupling than the corresponding hydrogen-bonded Ndelta proton from
      metmyoglobin. The unique residue Phe14 occludes binding of a sixth ligand in
      cytochrome c', and ENDOR from a proton of the functionally important Phe14 ring,
      approximately 3.3 A away from the heme iron, was detected. ENDOR of the nitrogen
      ligand hyperfine structure is a direct probe into the sigma-antibonding (d(z)(2))
      and (d(x)(2)-d(y)(2)) orbitals whose energies alter the relative stability and
      admixture of sextet and quartet states and whose electronic details were thus
      elucidated. ENDOR frequencies showed for cytochrome c' larger hyperfine couplings
      to the histidine nitrogen and smaller hyperfine couplings to the heme nitrogens
      than for high-spin ferric hemes. Both of these findings followed from the mixed
      spin ground state, which has less (d(x)(2)-d(y)(2)) character than have fully
      high-spin ferric heme systems.

PMID- 15984876
TI  - Reexamination of lead(II) coordination preferences in sulfur-rich sites:
      implications for a critical mechanism of lead poisoning.
AB  - Recent studies suggest that the developmental toxicity associated with childhood
      lead poisoning may be attributable to interactions of Pb(II) with proteins
      containing thiol-rich structural zinc-binding sites. Here, we report detailed
      structural studies of Pb(II) in such sites, providing critical insights into the
      mechanism by which lead alters the activity of these proteins. X-ray absorption
      spectroscopy of Pb(II) bound to structural zinc-binding peptides reveals that
      Pb(II) binds in a three-coordinate Pb(II)-S(3) mode, while Zn(II) is known to
      bind in a four-coordinate mode in these proteins. This Pb(II)-S(3) coordination
      in peptides is consistent with a trigonal pyramidal Pb(II)-S(3) model compound
      previously reported by Bridgewater and Parkin, but it differs from many other
      reports in the small molecule literature which have suggested Pb(II)-S(4) as a
      preferred coordination mode for lead. Reexamination of the published structures
      of these "Pb(II)-S(4)" compounds reveals that, in almost all cases, the
      coordination number of Pb is actually 5, 6, or 8. The results reported herein
      combined with this new review of published structures suggest that lead prefers
      to avoid four-coordination in sulfur-rich sites, binding instead as trigonal
      pyramidal Pb(II)-S(3) or as Pb(II)-S(5-8). In the case of structural zinc-binding
      protein sites, the observation that lead binds in a three-coordinate mode, and in
      a geometry that is fundamentally different from the natural coordination of zinc
      in these sites, explains why lead disrupts the structure of these peptides and
      thus provides the first detailed molecular understanding of the developmental
      toxicity of lead.

PMID- 15984877
TI  - Copper oxide nanocrystals.
AB  - It is well-known that inorganic nanocrystals are a benchmark model for
      nanotechnology, given that the tunability of optical properties and the
      stabilization of specific phases are uniquely possible at the nanoscale. Copper
      (I) oxide (Cu(2)O) is a metal oxide semiconductor with promising applications in
      solar energy conversion and catalysis. To understand the Cu/Cu(2)O/CuO system at
      the nanoscale, we have developed a method for preparing highly uniform
      monodisperse nanocrystals of Cu(2)O. The procedure also serves to demonstrate our
      development of a generalized method for the synthesis of transition metal oxide
      nanocrystals. Cu nanocrystals are initially formed and subsequently oxidized to
      form highly crystalline Cu(2)O. The volume change during phase transformation can
      induce crystal twinning. Absorption in the visible region of the spectrum gave
      evidence for the presence of a thin, epitaxial layer of CuO, which is blue
      shifted, and appears to increase in energy as a function of decreasing particle
      size. XPS confirmed the thin layer of CuO, calculated to have a thickness of
      approximately 5 A. We note that the copper (I) oxide phase is surprisingly well
      stabilized at this length scale.

PMID- 15984878
TI  - Diameter-selective solubilization of single-walled carbon nanotubes by reversible
      cyclic peptides.
AB  - We have utilized reversible cyclic peptides (RCPs)-peptides containing
      alternating l- and d-amino acids with N- and C-termini derivatized with thiol
      containing groups allowing reversible peptide cyclization-to solubilize and
      noncovalently functionalize carbon single-walled nanotubes (SWNTs) in aqueous
      solution. Solubilization occurs through wrapping of RCPs around the circumference
      of a SWNT, followed by the formation of head-to-tail covalent bonds, yielding
      closed rings on the nanotubes. By controlling the length of the RCPs, we have
      demonstrated limited diameter-selective solubilization of the SWNTs as revealed
      by UV/vis/NIR and Raman spectroscopies, as well as atomic force microscopy.

PMID- 15984879
TI  - Carbohydrate-based DNA ligands: sugar-oligoamides as a tool to study carbohydrate
      nucleic acid interactions.
AB  - Sugar-oligoamides have been designed and synthesized as structurally simple
      carbohydrate-based ligands to study carbohydrate-DNA interactions. The general
      design of the ligands 1-3 has been done as to favor the bound conformation of
      Distamycin-type gamma-linked covalent dimers which is a hairpin conformation.
      Indeed, NMR analysis of the sugar-oligoamides in the free state has indicated the
      presence of a percentage of a hairpin conformation in aqueous solution. The DNA
      binding activity of compounds 1-3 was confirmed by calf thymus DNA (ct-DNA) NMR
      titration. Interestingly, the binding of the different sugar-oligoamides seems to
      be modulated by the sugar configuration. Semiquantitative structural information
      about the DNA ligand complexes has been derived from NMR data. A competition
      experiment with Netropsin suggested that the sugar-oligoamide 3 bind to DNA in
      the minor groove. The NMR titrations of 1-3 with poly(dA-dT) and poly(dG-dC)
      suggested preferential binding to the ATAT sequence. TR-NOE NMR experiments for
      the sugar-oligoamide 3-ct-DNA complex both in D(2)O and H(2)O have confirmed the
      complex formation and given information on the conformation of the ligand in the
      bound state. The data confirmed that the sugar-oligoamide ligand is a hairpin in
      the bound state. Even more relevant to our goal, structural information on the
      conformation around the N-glycosidic linkage has been accessed. Thus, the sugar
      asymmetric centers pointing to the NH-amide and N-methyl rims of the molecule
      have been characterized.

PMID- 15984880
TI  - 5-endo-dig radical cyclizations: "the poor cousins" of the radical cyclizations
      family.
AB  - Kinetics and thermodynamics of 5-endo-dig radical cyclizations were studied using
      a combination of DFT computations and Marcus theory. When the reactant is
      stabilized by conjugation of the radical center with the bridge pi-system, the
      cyclization starts with reorientation of the radical orbital needed to reach the
      in-plane acetylene pi-orbital in the bond-forming step. This reorientation leads
      to loss of the above conjugative stabilization, increases the activation energy,
      and renders such cyclizations less exothermic. As a result, even when the radical
      needed for the 5-endo cyclization is formed efficiently, it undergoes either H
      abstraction or equilibration with an isomeric radical. Only when the bridging
      moiety is saturated or when intramolecular constraints prevent the overlap of the
      bridge pi-orbital and the radical center, 5-endo cyclizations may be able to
      proceed with moderate efficiency under conditions when H-abstraction is slow. The
      main remaining caveat in designing such geometrically constrained 5-endo-dig
      cyclizations is their sensitivity to strain effects, especially when polycyclic
      systems are formed. The strain effects can be counterbalanced by increasing the
      stabilization of the product (e.g., by introducing heteroatoms into the bridging
      moiety). Electronic effects of such substitutions can be manifested in various
      ways, ranging from aromatic stabilization to a hyperconjugative beta-Si effect.
      The 4-exo-dig cyclization is kinetically competitive with the 5-endo-dig process
      but less favorable thermodynamically. As a result, by proper design of reaction
      conditions, 5-endo-dig radical cyclizations should be experimentally feasible.

PMID- 15984881
TI  - Artificial oligopeptide scaffolds for stoichiometric metal binding.
AB  - Two artificial peptides with pendant pyridine or bipyridine ligands have been
      synthesized and incorporated into oligomeric strands that are analogous to
      peptide nucleic acid. Spectrophotometric titrations with Cu(2+) and Fe(2+) show
      that the oligomers bind stoichiometric quantities of transition metals based on
      the number of pendant ligands. The identities of the titration products are
      confirmed by high resolution mass spectrometry. In the case of the bipyridine
      tripeptides, the titration stoichiometry and mass spectra indicate that the metal
      ions form interstrand cross-links between two oligopeptides, creating duplex
      structures linked exclusively by metal ions. Calculated molecular structures of
      the metalated oligopeptides and duplexes indicate that the peptide backbone acts
      as a scaffold for the directed assembly of metal ions. Electron paramagnetic
      resonance spectroscopy of the Cu-containing molecules have varying degrees of
      electronic interaction based on their charge and supramolecular structure. Cyclic
      voltammetry of the Fe(2+)- and Cu(2+)-linked bpy oligopeptide duplexes shows that
      they possess unique electrochemical signatures based on the redox reactivity of
      the metal complex.

PMID- 15984882
TI  - Hole-induced quenching of triplet and singlet excitons in conjugated polymers.
AB  - Quantitative information on the mechanisms and rates of hole (radical cation)
      induced quenching of triplet and singlet excitons in the conjugated polymer
      poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] has been acquired by a
      new technique, fluorescence-voltage time-resolved single molecule spectroscopy
      (FV-TR-SMS). FV-TR-SMS measures the fluorescence intensity of a single conjugated
      polymer molecule that is embedded in a capacitor-like device while simultaneously
      modulating the bias on the device and the irradiation intensity. The results
      demonstrate that triplet excitons are efficiently quenched by holes in conjugated
      polymers for hole densities >10(16) charges/cm(3), while singlet excitons are
      quenched with a much lower efficiency. Detailed kinetic analysis shows that the
      greater efficiency for quenching of triplets by holes (compared to that for
      singlets) is due to a >10(6) times longer exciton lifetime for triplets. In fact,
      the results suggest that while singlet quenching is less efficient due to a much
      shorter singlet lifetime, the rate constant for the quenching of singlets by
      holes actually exceeds that for triplets by several orders of magnitude.

PMID- 15984884
TI  - Chemoenzymatic approach to enantiopure streptogramin B variants: characterization
      of stereoselective pristinamycin I cyclase from Streptomyces pristinaespiralis.
AB  - Streptogramin B antibiotics are cyclic peptide natural products produced by
      Streptomyces species. In combination with the synergistic group A component, they
      are "last line of defense" antimicrobial agents against multiresistant cocci. The
      racemization sensitivity of the phenylglycine (Phg(7)) ester is a complex
      challenge in total chemical synthesis of streptogramin B molecules. To provide
      fast and easy access to novel streptogramin antibiotics, we introduce a novel
      chemoenzymatic strategy in which diversity is generated by standard solid phase
      protocols and stereoselectivity by subsequent enzymatic cyclization. For this
      approach, we cloned, overproduced, and biochemically characterized the
      recombinant thioesterase domain SnbDE TE of the pristinamycin I nonribosomal
      peptide synthetase from Streptomyces pristinaespiralis. SnbDE TE catalyzes
      regioselective ring closure of linear peptide thioester analogues of
      pristinamycin I as well as stereoselective cyclization out of complex in situ
      racemizing substrate mixtures, enabling synthesis of Streptogramin B variants via
      a dynamic kinetic resolution assay. A remarkable substrate tolerance was detected
      for the enzymatic cyclization including all the seven positions of the peptide
      backbone. Interestingly, SnbDE TE was observed to be the first cyclase from a
      macrolactone forming NRPS which is additionally able to catalyze
      macrolactamization of peptide thioester substrates. An N-methylated peptide bond
      between positions 4 and 5 is mandatory for a high substrate turnover. The
      presented strategy is potent to screen for analogues with improved activity and
      guides our understanding of structure--activity relationships in the important
      class of streptogramin antibiotics.

PMID- 15984883
TI  - Three challenges toward the assignment of absolute configuration of gymnocin-B.
AB  - The absolute configuration of gymnocin-B has been determined to be (S)-10 and (S)
      37. Three challenges toward the configurational assignment of this largest of the
      polyether marine toxin include (i) introduction of p-(meso-triphenylporphyrin)
      cinnamate group (TPPcinnamate) on sterically hindered 10-, 37-hydroxyls under
      mild conditions, (ii) conformational analysis in the presence of TPPcinnamates at
      C-10 and C-37 positions on the flexible seven-membered rings embodied in a large
      polyether ladder-like scaffold structure, and (iii) determination of the
      chirality at C-10 and C-37 on the basis of porphyrin/porphyrin circular dichroism
      exciton-coupled interaction over a large distance. The experimentally obtained
      positive exciton couplet by CD and FDCD of the bis-TPPcin derivative of gymnocin
      B is in good agreement with that of theoretically calculated CD of the MMFF
      optimized structures, by employing DeVoe's coupled oscillator approach, thus
      establishing the full absolute configuration of gymnocin-B.

PMID- 15984885
TI  - Ball-and-socket stacking of supercharged geodesic polyarenes: bonding by
      interstitial lithium ions.
AB  - Unprecedented supramolecular stacks of highly reduced geodesic pi-systems were
      prepared by the reduction of the derivatized fullerenes Me(5)C(60)H and
      Ph(5)C(60)H and corannulene with lithium metal (R(5)C(60)(5)(-)/Cor(4)(
      )/9Li(+)). The host--guest assemblies form because of the enhanced electrostatic
      interactions between the lithium cations and the anionic moieties, in addition to
      the structural compatibility between the curved hydrocarbons. The high stability
      of these new supramolecular assemblies (heterodimers) enables the introduction of
      another organization motif to the system. This is achieved by using tethered
      corannulenes as host molecules, which leads to the formation of tethered bis
      heterodimers ((Me(5)C(60)(5)(-)/Cor(4)(-))(2)(CH(2))(8)/18Li(+)).

PMID- 15984886
TI  - Bioresponsive hydrogel microlenses.
AB  - We report investigations of bioresponsive hydrogel microlenses as a new protein
      detection technology. Stimuli-responsive poly(N-isopropylacrylamide-co-acrylic
      acid) (pNIPAm-co-AAc) microgels have been synthesized via free-radical
      precipitation polymerization. These hydrogel microparticles were then
      functionalized with biotin via EDC coupling. Hydrogel microlenses were prepared
      from the particles via Coulombic assembly onto a silane-modified glass substrate.
      Arrays containing both pNIPAm-co-AAc microgels (as an internal control) and
      biotinylated pNIPAm-co-AAc microgels were then used to detect multivalent binding
      of both avidin and polyclonal anti-biotin. Protein binding was determined by
      monitoring the optical properties of the microlenses using a brightfield optical
      microscopy technique. The microlens method is shown to be very specific for the
      target protein, with no detectable interference from nonspecific protein binding.
      Finally, the reversibility of the hydrogel microlens assay has been studied in
      the case of anti-biotin to determine the potential application of the microlens
      assay technology in a displacement-type assay. These results suggest that the
      microlens method may be an appropriate one for label-free detection of proteins
      or small molecules via displacement of tethered protein--ligand pairs.

PMID- 15984887
TI  - Artificial metalloprotease with active site comprising aldehyde group and
      Cu(II)cyclen complex.
AB  - To design artificial proteases that cleave peptide backbones of a wide range of
      proteins at selected sites, artificial active sites comprising the Cu(II) complex
      of cyclen (Cu(II)Cyc) and aldehyde group were synthesized on a cross-linked
      polystyrene. The aldehyde group was employed as the binding site in view of its
      ability of reversible formation of imine bonds with epsilon-amino groups of Lys
      residues exposed on the surface of proteins and Cu(II)Cyc as the catalytic group
      for peptide hydrolysis. The two polymeric artificial metalloproteases synthesized
      in the present study cleaved all of the protein substrates examined (myoglobin,
      gamma-globulin, bovine serum albumin, human serum albumin, lysozyme, and
      ovalbumin), manifesting saturation kinetic behavior. At 50 degrees C and pH 9.0
      or 9.5, K(m) was (1.3-22) x 10(-)(4) M, comparable to those of natural proteases,
      and k(cat) was (6.0-25) x 10(-)(4) s(-)(1), corresponding to half-lives of 4.6-19
      min. Intermediacy of the imine complexes formed between the aldehyde group of the
      catalyst and the epsilon-amino groups of Lys residues of the substrates was
      confirmed by the trapping experiment with NaB(OAc)(3)H. MALDI-TOF MS of the
      proteolytic reaction mixtures revealed formation of various cleavage products.
      Structures of some of the cleavage products were determined by using
      carboxypeptidase A and trypsin. Among various cleavage sites thus identified,
      Gln(91)-Ser(92) and Ala(94)-Thr(95) were the major initial cleavage sites in the
      degradation of myoglobin by the two catalysts. The selective cleavage of Gln(91)
      Ser(92) and Ala(94)-Thr(95) was attributed to general acid assistance in peptide
      cleavage by Tyr(146) located in proximity to the two peptide bonds. Broad
      substrate selectivity, high cleavage-site selectivity, and high proteolytic rate
      are achieved, therefore, by positioning the aldehyde group in proximity to
      Cu(II)Cyc attached to a cross-linked polystyrene.

PMID- 15984888
TI  - Chiral rodlike platinum complexes, double helical chains, and potential
      asymmetric hydrogenation ligand based on "linear" building blocks: 1,8,9,16
      tetrahydroxytetraphenylene and 1,8,9,16
      tetrakis(diphenylphosphino)tetraphenylene.
AB  - This paper is concerned with the synthesis of 1,8,9,16-tetrahydroxytetraphenylene
      (3a) via copper(II)-mediated oxidative coupling, its resolution to optical
      antipodes, and its conversion to 1,8,9,16
      tetrakis(diphenylphosphino)tetraphenylene (3b). On the basis of these chiral
      "linear" building blocks, three rodlike chiral complexes, triblock (R,R,R,R)-17
      and (S,S,S,S)-20 and pentablock (R,R,R,R,R,R,R,R)-22, were constructed. As a
      hydrogen bond donor, racemic and optically active 3a was allowed to assemble with
      linear acceptors to afford highly ordered structures. A 1:1 adduct of 4,4'
      bipyridyl and (+/-)-3a exists in a dimeric form of 3a linked by 4,4'-bipyridyl
      through hydrogen bonds. Pyrazine serves as a short linker between achiral
      parallel chains each formed by (+/-)-3a, while self-assembly of homochiral 3a
      into alternate parallel chains occurs in the adduct of 5,5'-dipyrimidine with (+/
      )-3a. Self-assembly of (S,S)-3a or (R,R)-3a with 4,4'-dipyridyl yielded a packing
      of chiral double helical chains formed by chiral tetrol 3a molecules. A novel
      chiral ligand, (S,S)-23, derived from 3a was used in the asymmetric catalytic
      hydrogenation of alpha-acetamidocinnamate, yielding up to 99.0% ee and 100%
      conversion.

PMID- 15984889
TI  - Spectroscopic characterization of site-specific [Fe(4)S(4)] cluster chemistry in
      ferredoxin:thioredoxin reductase: implications for the catalytic mechanism.
AB  - Light regulation of enzyme activities in oxygenic photosynthesis is mediated by
      ferredoxin:thioredoxin reductase (FTR), a novel class of disulfide reductase with
      an active site comprising a [Fe(4)S(4)](2+) cluster and an adjacent disulfide,
      that catalyzes reduction of the thioredoxin disulfide in two sequential one
      electron steps using a [Fe(2)S(2)](2+/+) ferredoxin as the electron donor. In
      this work, we report on spectroscopic (EPR, VTMCD, resonance Raman, and
      Mossbauer) and redox characterization of the active site of FTR in various forms
      of the enzyme, including wild-type FTR, point-mutation variants at each of the
      active-site cysteine residues, and stable analogues of the one-electron-reduced
      FTR-Trx heterodisulfide intermediate. The results reveal novel site-specific
      Fe(4)S(4)-cluster chemistry in oxidized, one-electron-reduced, and two-electron
      reduced forms of FTR. In the resting enzyme, a weak interaction between the
      Fe(4)S(4) cluster and the active-site disulfide promotes charge buildup at a
      unique Fe site and primes the active site to accept an electron from ferredoxin
      to break the disulfide bond. In one-electron-reduced analogues, cleavage of the
      active-site disulfide is accompanied by coordination of one of the cysteine
      residues that form the active-site disulfide to yield a [Fe(4)S(4)](3+) cluster
      with two cysteinate ligands at a unique Fe site. The most intriguing result is
      that two-electron-reduced FTR in which the disulfide is reduced to a dithiol
      contains an unprecedented electron-rich [Fe(4)S(4)](2+) cluster comprising both
      valence-delocalized and valence-localized Fe(2+)Fe(3+) pairs. These results
      provide molecular level insights into the catalytic mechanism of FTR, and two
      viable mechanisms are proposed.

PMID- 15984890
TI  - Cp(*)RuCl-catalyzed formal intermolecular cyclotrimerization of three
      unsymmetrical alkynes through a boron temporary tether: regioselective four
      component coupling synthesis of phthalides.
AB  - Highly substituted phthalides were efficiently synthesized by sequential
      Cp(*)RuCl-catalyzed cyclotrimerization of alkynylboronates, propargyl alcohols,
      and terminal alkynes and palladium(II)-catalyzed carbonylation of the resultant
      arylboronates. The intermediate arylboronate was isolated and unambiguously
      characterized by X-ray crystallography. The perfect regioselectivity of the
      ruthenium-catalyzed formal intermolecular cyclotrimerization was discussed on the
      basis of the density functional calculations of a boraruthenacycle intermediate.

PMID- 15984891
TI  - Representing receptor flexibility in ligand docking through relevant normal
      modes.
AB  - Inspired by the current representation of the ligand-receptor binding process, a
      normal-mode-based methodology is presented to incorporate receptor flexibility in
      ligand docking and virtual screening. However, the systematic representation of
      the deformation space grows geometrically with the number of modes, and
      furthermore, midscale loop rearrangements like those found in protein kinase
      binding pockets cannot be accounted for with the first lowest-frequency modes. We
      thus introduced a measure of relevance of normal modes on a given region of
      interest and showed that only very few modes in the low-frequency range are
      necessary and sufficient to describe loop flexibility in cAMP-dependent protein
      kinase. We used this approach to generate an ensemble of representative receptor
      backbone conformations by perturbing the structure along a combination of
      relevant modes. Each ensemble conformation is complexed with known non-native
      binders to optimize the position of the binding-pocket side chains through a full
      flexible docking procedure. The multiple receptor conformations thus obtained are
      used in a small-scale virtual screening using receptor ensemble docking. We
      evaluated this algorithm on holo and apo structures of cAMP-dependent protein
      kinase that exhibit backbone rearrangements on two independent loop regions close
      to the binding pocket. Docking accuracy is improved, since the ligands considered
      in the virtual screening docked within 1.5 A to at least one of the structures.
      The discrimination between binders and nonbinders is also enhanced, as shown by
      the improvement of the enrichment factor. This constitutes a new step toward the
      systematic integration of flexible ligand-flexible receptor docking tools in
      structure-based drug discovery.

PMID- 15984893
TI  - Blue copper model complexes with distorted tetragonal geometry acting as
      effective electron-transfer mediators in dye-sensitized solar cells.
AB  - The electron self-exchange rate constants of blue copper model complexes, [(-)
      sparteine-N,N'](maleonitriledithiolato-S,S')copper ([Cu(SP)(mmt)])(0/)(-),
      bis(2,9-dimethy-1,10-phenanthroline)copper ([Cu(dmp)(2)](2+/+)), and bis(1,10
      phenanthroline)copper ([Cu(phen)(2)](2+/+)) have been determined from the rate
      constants of electron transfer from a homologous series of ferrocene derivatives
      to the copper(II) complexes in light of the Marcus theory of electron transfer.
      The resulting electron self-exchange rate constant increases in the order:
      [Cu(phen)(2)](2+/+) < [Cu(SP)(mmt)](0/)(-) < [Cu(dmp)(2)](2+/+), in agreement
      with the order of the smaller structural change between the copper(II) and
      copper(I) complexes due to the distorted tetragonal geometry. The dye-sensitized
      solar cells (DSSC) were constructed using the copper complexes as redox couples
      to compare the photoelectrochemical responses with those using the conventional
      I(3)(-)/I(-) couple. The light energy conversion efficiency (eta) values under
      illumination of simulated solar light irradiation (100 mW/cm(2)) of DSSCs using
      [Cu(phen)(2)](2+/+), [Cu(dmp)(2)](2+/+), and [Cu(SP)(mmt)](0/)(-) were recorded
      as 0.1%, 1.4%, and 1.3%, respectively. The maximum eta value (2.2%) was obtained
      for a DSSC using the [Cu(dmp)(2)](2+/+) redox couple under the light irradiation
      of 20 mW/cm(2) intensity, where a higher open-circuit voltage of the cell was
      attained as compared to that of the conventional I(3)(-)/I(-) couple.

PMID- 15984892
TI  - Stereochemistry of beta-deuterium isotope effects on amine basicity.
AB  - Secondary beta-deuterium isotope effects on amine basicities are measured using a
      remarkably precise NMR titration method. Deuteration is found to increase the
      basicity of methylamine, dimethylamine, benzylamine, N,N-dimethylaniline, 2
      methyl-2-azanorbornane, and pyrrolizidine. The increase in dimethylamine arises
      entirely from enthalpy, contrary to a previous report. The method permits a
      determination of intramolecular isotope effects in 1-benzyl-4-methylpiperidine
      and 2-benzyl-2-azanorbornane. It is found that deuteration has a larger isotope
      effect when either antiperiplanar or synperiplanar to a lone pair, but the
      synperiplanar effect is smaller, as confirmed by computations. The isotope effect
      is attributed to a lowered zero-point energy of a C-H bond adjacent to an amine
      nitrogen, arising from delocalization of either a syn or an anti lone pair, and
      with no detectable angle-independent inductive effect.

PMID- 15984894
TI  - Rapid cycling bipolar disorder: clinical characteristics and treatment options.
AB  - Approximately one of six patients who seek treatment for bipolar disorder present
      with a rapid cycling pattern. In comparison with other patients who have bipolar
      disorder, these individuals experience more affective morbidity in both the
      immediate and distant future and are more likely to experience recurrences
      despite treatment with lithium or anticonvulsants. Particular care should be
      given to distinguishing rapid cycling bipolar disorder from attention-deficit
      hyperactivity disorder in children or adolescents and from borderline personality
      disorder in adults. Perhaps four of five cases of rapid cycling resolve within a
      year, but the pattern may persist for many years in the remaining patients. As
      with bipolar disorder in general, depressive symptoms produce the most morbidity
      over time. Controlled studies have not established that antidepressants provoke
      switching or rapid cycling, but neither have they been shown consistently to have
      benefits in bipolar illness. Successful management will often require a sequence
      of trials with mood stabilizer drugs, beginning with lithium in treatment-naive
      patients. Efforts to minimise adverse effects, and the recognition that full
      benefits may not be apparent for several months, will make the premature
      abandonment of a potentially helpful treatment less likely. Placebo-controlled
      studies so far provide the most support for the use of lithium and lamotrigine as
      prophylactic agents. The combination of lithium and carbamazepine, valproate or
      lamotrigine for maintenance has some support from controlled studies, as does the
      adjunctive use of olanzapine.

PMID- 15984895
TI  - Behavioural manifestations of anabolic steroid use.
AB  - The use of anabolic androgenic steroids (AAS) for gains in strength and muscle
      mass is relatively common among certain subpopulations, including athletes,
      bodybuilders, adolescents and young adults. Adverse physical effects associated
      with steroid abuse are well documented, but more recently, increased attention
      has been given to the adverse psychiatric effects of these compounds. Steroids
      may be used in oral, 17alpha-alkylated, or intramuscular, 17beta-esterified,
      preparations. Commonly, steroid users employ these agents at levels 10- to 100
      fold in excess of therapeutic doses and use multiple steroids simultaneously, a
      practice known as 'stacking'. Significant psychiatric symptoms including
      aggression and violence, mania, and less frequently psychosis and suicide have
      been associated with steroid abuse. Long-term steroid abusers may develop
      symptoms of dependence and withdrawal on discontinuation of AAS. Treatment of AAS
      abusers should address both acute physical and behavioural symptoms as well as
      long-term abstinence and recovery. To date, limited information is available
      regarding specific pharmacological treatments for individuals recovering from
      steroid abuse. This paper reviews the published literature concerning the
      recognition and treatment of behavioural manifestations of AAS abuse.

PMID- 15984897
TI  - SSRIs in pregnancy and lactation: emphasis on neurodevelopmental outcome.
AB  - The aim of this review was to assess existing information about the long-term
      neurocognitive development of children whose mothers took SSRIs during pregnancy
      and/or breastfeeding. The available literature consists of 11 studies (examining
      a total of 306 children) that demonstrate no impairment of infant
      neurodevelopment following prenatal and/or postnatal exposure to SSRIs, and two
      studies (examining 81 children) that suggest possible unwanted effects of fetal
      SSRI exposure. These unwanted effects included subtle effects on motor
      development and motor control. Thus, the available data are not unanimous in
      excluding possible long-term detrimental neurodevelopmental sequelae of
      intrauterine exposure to SSRIs. However, it is clear that the research suggesting
      a lack of adverse events on infants' neurocognitive development is much more
      numerous and methodologically better conducted than the studies showing possible
      unwanted effects. Nevertheless, all reviewed studies had procedural inadequacies,
      and the screening instruments used have limitations, especially in the evaluation
      of infants. Furthermore, it is not advisable to extend the generalisations
      emerging from the findings of a few trials to every infant. Some infants may
      experience difficulties in metabolising the drugs and/or their metabolites, so
      the benign outcome described for most infants may not occur. Thus, the findings
      emerging from the reports are inconclusive and are not able to fully clarify the
      repercussions of maternal SSRI treatment on infants' long-term neurocognitive
      development. Further large, simple and well designed, randomised, prospective
      studies will be required for this purpose. These should also be of adequate
      length and performed using reproducible neurophysiological parameters in order to
      firmly establish the safety of these medications.

PMID- 15984896
TI  - Place of drug therapy in the treatment of carotid stenosis.
AB  - Carotid stenosis is an important cause of transient ischaemic attacks and stroke.
      The cause of carotid stenosis is most often atherosclerosis; contributing to the
      pathogenesis of the lesion are endothelial injury, inflammation, lipid
      deposition, plaque formation, fibrin, platelets and thrombin. Carotid stenosis
      accounts for 10-20% of cases of brain infarction, depending on the population
      studied. Despite successful treatment of selected patients who have had an acute
      ischaemic stroke with tissue plasminogen activator and the promise of other
      experimental therapies, prevention remains the best approach to reducing the
      impact of ischaemic stroke. High-risk or stroke-prone patients can be identified
      and targeted for specific interventions. At this juncture, treatment of carotid
      stenosis is a well established therapeutic target and a pillar of stroke
      prevention. There are two main strategies for the treatment of carotid stenosis.
      The first approach is to stabilise or halt the progression of the carotid plaque
      through risk factor modification and medication. Hypertension, diabetes mellitus,
      smoking, obesity and high cholesterol levels are closely associated with carotid
      stenosis and stroke; control of these factors may decrease the risk of plaque
      formation and progression. The second approach is to eliminate or reduce carotid
      stenosis through carotid endarterectomy or carotid angioplasty and stenting.
      Carotid endarterectomy, which is the mainstay of therapy for severe carotid
      stenosis, is beyond the scope of this review. Anticoagulants seem to play little
      role (if any) in the medical (i.e. non-surgical) treatment of carotid stenosis.
      Adoption of a healthy lifestyle combined with the reduction of risk factors has
      been shown to lead to a reduction in the extent of carotid stenosis. The medical
      treatment of carotid stenosis should be based on the triad of the reduction of
      risk factors, patient education, and use of antiplatelet agents.

PMID- 15984898
TI  - Cost-effectiveness analysis of rizatriptan and sumatriptan versus Cafergot in the
      acute treatment of migraine.
AB  - BACKGROUND: Both ergotamine and selective serotonin 5-HT(1B/1D) receptor agonists
      ('triptans') are currently used in the treatment of moderate to severe migraine.
      Ergotamine is a traditional therapy with a lower drug acquisition cost compared
      with triptans. It has been shown that triptans are more efficacious than
      ergotamine, but the higher acquisition costs and shorter duration of action are
      disadvantages of triptans compared with ergotamine. OBJECTIVE: The purpose of
      this study was to provide a comparison of the cost-effectiveness of rizatriptan
      10 mg and sumatriptan 50 mg tablets with that of a fixed-dose combination of
      ergotamine tartrate plus caffeine (Cafergot) in the treatment of an acute
      migraine attack. The cost-effectiveness of rizatriptan in comparison with
      sumatriptan was also assessed. METHODS: Three separate decision tree models were
      developed (model 1: rizatriptan vs Cafergot; model 2: sumatriptan vs Cafergot;
      model 3: rizatriptan vs sumatriptan). The time horizon was 1 year. Cost
      effectiveness analysis was conducted from the societal perspective using cost and
      effectiveness estimates from the literature. All costs were converted to US
      dollars (2003). The cost-effectiveness ratio was expressed as incremental cost
      per quality-adjusted life-year (QALY) gained. RESULTS: Base case evaluation
      showed that both rizatriptan and sumatriptan dominated Cafergot. The net annual
      saving associated with use of rizatriptan was US dollars 622.98 per patient, with
      an incremental QALY of 0.001. Use of sumatriptan resulted in a saving of US
      dollars 620.90 and an increase in QALY. The cost-effective ratios were not
      sensitive to changes in key variables such as efficacy, utility, drug costs,
      hospitalisation cost and patient preference over alternative therapies. The study
      further showed that rizatriptan is more cost effective than sumatriptan, as
      evidenced by its lower cost and greater effectiveness. Sensitivity analysis
      showed that the cost-effectiveness ratios were sensitive to moderate changes in
      drug efficacy. CONCLUSION: Rizatriptan and sumatriptan were less costly and more
      effective than Cafergot in the treatment of an acute migraine attack. Rizatriptan
      was somewhat less costly and more effective than sumatriptan. Additional quality
      of-life studies are needed to confirm the benefits of using triptans in the
      management of migraine.

PMID- 15984899
TI  - The use of human deoxyribonuclease (rhDNase) in the management of cystic
      fibrosis.
AB  - In patients with cystic fibrosis (CF), the poor clearance of airway secretions
      promotes recurrent cycles of pulmonary infection and inflammation. In recent
      years, novel drugs have been developed to alter the properties of the secretions
      in an attempt to aid chest physiotherapy in improving airway clearance. Once
      daily nebulised recombinant human deoxyribonuclease (rhDNase; dornase alfa;
      Pulmozyme) is the most widely used mucoactive therapy in patients with CF. It has
      been shown to reduce the viscoelasticity of sputum from patients with CF and
      enhance the clearance of secretions. Clinical trials have shown rhDNase to be a
      well tolerated treatment that improves pulmonary function and reduces respiratory
      exacerbations. However, the response to treatment is heterogeneous and only a
      proportion of patients with CF actually benefit from the treatment. At present,
      we are unable to predict which patients will benefit from rhDNase. Many CF
      centers have developed formal n-of-1 trials of treatment to find out who benefits
      and to justify prescribing the agent. rhDNase is an expensive therapy and is
      mainly used in patients over the age of 5 years with moderate to severe lung
      disease. However, studies have shown that rhDNase may be useful in patients with
      milder lung disease. Comparisons with another mucoactive drug, hypertonic saline,
      have shown rhDNase to be more effective. Recently, it has been shown that giving
      rhDNase on an alternate-day basis, rather than daily, is equally effective,
      potentially reducing costs and treatment time.

PMID- 15984900
TI  - Radiolabeled peptides in oncology: role in diagnosis and treatment.
AB  - There has been an exponential growth in the development of radiolabeled peptides
      for diagnostic and therapeutic applications in the last decade. The automated
      means of synthesizing these compounds in large quantities and the simplified
      methods of purifying, characterizing, and optimizing them have kindled attention
      to peptides as carrier molecules. These new techniques have accelerated the
      commercial development of radiolabelled peptides, which has provided additional
      radiopharmaceuticals for the nuclear medicine community. Peptides have many key
      properties including fast clearance, rapid tissue penetration, and low
      antigenicity, and can be produced easily and inexpensively. However, there may be
      problems with in vivo catabolism, unwanted physiologic effects, and chelate
      attachment. Radiolabeled peptides have made their greatest impact in the
      management of relatively rare neuroendocrine malignancies. Indeed, Indium-111
      ((111)In)-pentetreotide ((111)In-DTPA-octreotide, Octreoscan), which binds to
      somatostatin receptors (SSTRs), has become the diagnostic 'gold standard' in
      these diseases. However, (111)In-pentetreotide has been less successful in the
      diagnosis of other more prevalent diseases in which SSTRs are upregulated.
      Technetium-99m (99mTc)-depreotide (NeoTect), a 99mTc-labeled SSTR-analog, could
      have wider impact since it has high sensitivity and specificity for lung cancer
      lesion detection. However, this impact may be minimized by the increased
      availability of positron emission tomography imaging with Fluorine-18 (18F)
      flourodeoxyglucose, which has similar sensitivity and specificity for lesion
      identification in this disease, and is currently more widely used. The receptors
      for bombesin, alpha-melanocyte-stimulating hormone, neurotensin, and the integrin
      alpha(v)beta3, are under active investigation as targets for radiolabelled
      peptides, but are still in the pre-clinical stage. Compounds directed at the
      cholecystokinin-B/gastrin receptor have shown promising results in clinical
      trials in humans. Radiolabelled peptide therapy is usually indicated for patients
      with widespread disease that is not amenable to focused radiation therapy or is
      refractory to chemotherapy. Phase I/II studies using various radiolabelled
      peptides (including (111)In-pentetreotide, Yttrium-90 [90Y]-DOTA-Phe1-Tyr3
      octreotide, 90Y-DOTA-lanreotide, and Lutetium-177 [177Lu]-DOTA-octreotate) for
      the treatment of patients with neuroendocrine malignancy are in progress. Over
      400 patients have been treated, and the response rate has ranged from 60% to 75%,
      although few patients have had a complete response. Patients have been given
      individual doses ranging from 2 to 11 GBq with a slow infusion every 4-8 weeks
      (up to 12 times). The kidney is the dose-limiting organ and most patients
      experience a transient decline in blood cell counts. A concomitant infusion of an
      amino acid mixture can reduce kidney toxicity and increase the effective tumor
      dose. Other peptides currently under investigation, some of which have shown
      promising results, include Rhenium-188 (188Re)-P2045 and 90Y-alpha(v)beta3
      antagonist.

PMID- 15984901
TI  - Oral delivery of peptide drugs: barriers and developments.
AB  - A wide variety of peptide drugs are now produced on a commercial scale as a
      result of advances in the biotechnology field. Most of these therapeutic peptides
      are still administered by the parenteral route because of insufficient absorption
      from the gastrointestinal tract. Peptide drugs are usually indicated for chronic
      conditions, and the use of injections on a daily basis during long-term treatment
      has obvious drawbacks. In contrast to this inconvenient and potentially
      problematic method of drug administration, the oral route offers the advantages
      of self-administration with a high degree of patient acceptability and
      compliance. The main reasons for the low oral bioavailability of peptide drugs
      are pre-systemic enzymatic degradation and poor penetration of the intestinal
      mucosa. A considerable amount of research has focused on overcoming the
      challenges presented by these intestinal absorption barriers to provide effective
      oral delivery of peptide and protein drugs. Attempts to improve the oral
      bioavailability of peptide drugs have ranged from changing the physicochemical
      properties of peptide molecules to the inclusion of functional excipients in
      specially adapted drug delivery systems. However, the progress in developing an
      effective peptide delivery system has been hampered by factors such as the
      inherent toxicities of absorption-enhancing excipients, variation in absorption
      between individuals, and potentially high manufacturing costs. This review
      focuses on the intestinal barriers that compromise the systemic absorption of
      intact peptide and protein molecules and on the advanced technologies that have
      been developed to overcome the barriers to peptide drug absorption.

PMID- 15984902
TI  - The science of megestrol acetate delivery: potential to improve outcomes in
      cachexia.
AB  - Cachexia, usually defined as the loss of >5% of an individual's baseline
      bodyweight over 2-6 months, occurs with a number of diseases that includes not
      only AIDS and advanced cancer but also chronic heart failure, rheumatoid
      arthritis, chronic obstructive pulmonary disease, Crohn disease, and renal
      failure. Anorexia is considered a key component of the anorexia-cachexia
      syndrome. Progestogens, particularly megestrol acetate, are commonly used to
      treat anorexia-cachexia. The mechanism of action of megestrol is believed to
      involve stimulation of appetite by both direct and indirect pathways and
      antagonism of the metabolic effects of the principal catabolic cytokines. Because
      the bioavailability of megestrol acetate directly affects its efficacy and
      safety, the formulation was refined to enhance its pharmacokinetics. Such efforts
      yielded megestrol acetate in a tablet form, followed by a concentrated oral
      suspension form, and an oral suspension form developed using nanocrystal
      technology. Nanocrystal technology was designed specifically to optimize drug
      delivery and enhance the bioavailability of drugs that have poor solubility in
      water. Megestrol acetate nanocrystal oral suspension is currently under review by
      the US FDA for the treatment of cachexia in patients with AIDS. Preclinical
      pharmacokinetic data suggest that the new megestrol acetate formulation has the
      potential to significantly shorten the time to clinical response and thus may
      improve outcomes in patients with anorexia-cachexia.

PMID- 15984903
TI  - Anakinra: a review of its use in the management of rheumatoid arthritis.
AB  - Anakinra (Kineret) is the first biologic drug that has been developed
      specifically as an interleukin (IL)-1 receptor antagonist (Ra) and is derived
      from an endogenous IL-1Ra. The drug blocks the activity of IL-1 in synovial
      joints, reducing the inflammatory and joint destructive processes associated with
      rheumatoid arthritis (RA). In randomized, placebo-controlled trials of up to 52
      weeks' duration, anakinra has shown efficacy both as monotherapy and in
      combination with other disease-modifying antirheumatic drugs (DMARDs) in adults
      with RA. It is subcutaneously administered and is generally well tolerated.
      Anakinra offers a useful addition to the range of drugs available for the
      treatment of RA.

PMID- 15984904
TI  - Is the effect of antihypertensive drugs on platelet aggregability and
      fibrinolysis clinically relevant?
AB  - Hypertension is associated with decreased fibrinolytic potential, mainly
      expressed as elevated plasma plasminogen activator inhibitor type 1 (PAI-1)
      levels, and increased platelet aggregability, which may account in part for the
      increased risk of atherosclerosis and its clinical complications in hypertensive
      patients. The effects of antihypertensive drugs on this prothrombotic state have
      been investigated and controversial findings have been reported, possibly because
      of differences in study designs, patients selected, and methodology used. Scarce
      and conflicting data exist about the effects of diuretics and beta-adrenoceptor
      antagonists on the fibrinolytic system, whereas ACE inhibitors have generally
      been reported to improve the fibrinolytic balance by decreasing plasma PAI-1
      levels, calcium channel antagonists have been shown to increase tissue
      plasminogen activator (tPA) activity, and angiotensin II type 1 (AT(1)) receptor
      antagonists seem to exert neutral effects. beta-Adrenoceptor antagonists, calcium
      channel antagonists, and AT(1)-receptor antagonists have been reported to exert
      anti-aggregatory effects on platelets, while contrasting data exist about the
      influence of ACE inhibitors. Clinical implications of the changes induced by
      antihypertensive drugs on the fibrinolytic balance and platelet function are
      still debated. In particular, the question of whether these changes may translate
      into different degrees of cardiovascular protection in hypertensive patients
      remains unanswered. While awaiting more information from clinical trials, the
      choice of antihypertensive drugs, particularly in high-risk patients, should take
      into account effects beyond their BP-lowering efficacy. Selected agents should
      have a favorable, or at least neutral, impact on fibrinolytic function and
      platelet activity.

PMID- 15984905
TI  - Therapeutic potential of monteplase in acute myocardial infarction.
AB  - Thrombolysis with conventional thrombolytic agents prior to percutaneous coronary
      intervention (PCI) has had no impact on the treatment of acute myocardial
      infarction (AMI). However, the development of mutant tissue type plasminogen
      activators (mt-PA) has prompted us to reassess the combination of thrombolysis
      and PCI. Monteplase is a newly developed mt-PA that can be administered as a
      single intravenous bolus injection. The results of the COMA (COmbining Monteplase
      with Angioplasty) trial, suggest that monteplase administration prior to emergent
      PCI in AMI improves 6-month outcomes and possibly the long-term prognosis of
      myocardial infarction. Combining monteplase administration on presentation at a
      community hospital with prompt transfer to a tertiary center for PCI would be an
      ideal strategy for the treatment of AMI.

PMID- 15984906
TI  - The prevention and management of cardiovascular complications of chemotherapy in
      patients with cancer.
AB  - Cardiac toxicity of chemotherapeutic agents is a rapidly evolving area of
      increasing significance because of the increasing pool of long-term cancer
      survivors. The spectrum of cardiotoxicity with chemotherapeutic agents includes
      hypertension, QTc prolongation, acute cardiomyopathy, and bradyarrhythmias. The
      most common issue to arise has been cardiomyopathy with anthracyclines.
      Preventative strategies that have met with some success have included the use of
      less cardiotoxic analogs such as epirubicin and liposomal anthracycline
      preparations. The cardioprotectant agent dexrazoxane reduces cardiomyopathy but
      there are significant toxicity issues. Therefore, the main strategy for
      preventing cardiotoxicity remains careful monitoring with radionuclide
      angiography or echocardiography. The role of investigational markers of
      myocardial injury, such as troponin T or brain natriuretic peptide, remains of
      great interest. Management is according to conventional management of congestive
      heart failure. Trastuzumab is an antibody therapy directed against the human
      epidermal growth factor receptor-2 (HER2) receptor, which increases survival in
      patients with metastatic breast cancer and is under evaluation in the adjuvant
      setting. It also causes a decrease in left ventricular ejection fraction (LVEF)
      in a minority of patients. Incidence is increased if trastuzumab is given in
      conjunction with paclitaxel or anthracyclines. It differs from anthracycline
      cardiotoxicity in that it is not cumulative dose-dependent and often improves
      after withdrawal of treatment. Re-treatment with trastuzumab is often possible.
      Novel agents under development offer a different spectrum of toxicity to existing
      anticancer drugs and it appears likely that cardiovascular toxicity will be an
      important issue for many of these drugs, particularly those that target the tumor
      vasculature.

PMID- 15984907
TI  - Neuroprotection with angiotensin receptor antagonists: a review of the evidence
      and potential mechanisms.
AB  - The peptide hormone angiotensin (A)-II, the major effector peptide of the renin
      angiotensin system (RAS), is well established to play a pivotal role in the
      systemic regulation of blood pressure, fluid, and electrolyte homeostasis. Recent
      biochemical and neurophysiologic studies have documented local intrinsic
      angiotensin-generating systems in organs and tissues such as the brain, retina,
      bone marrow, liver, and pancreas. The locally generated angiotensin peptides have
      multiple and novel actions including stimulating cell growth and anti
      proliferative and/or antiapoptotic actions. In the mammalian brain, all
      components of the RAS are present including angiotensin receptor subtypes 1
      (AT(1)) and 2 (AT(2)). A-II exerts most of its well defined physiologic and
      pathophysiologic actions, including those on the central and peripheral nervous
      system, through its AT(1) receptor subtype. While the AT(1) receptor is
      responsible for the classical effects of A-II, it has been found that the AT(2)
      receptor is linked to totally different signalling mechanisms and this has
      revealed hitherto unknown functions of A-II. AT(2) receptors are expressed at low
      density in many healthy adult tissues, but are upregulated in a variety of human
      diseases. This receptor not only contributes to stroke-related pathologic
      mechanisms (e.g. hypertension, atherothrombosis, and cardiac hypertrophy) but may
      also be involved in post-ischemic damage to the brain. It has been reported that
      the AT(2) receptor regulates several functions of nerve cells, e.g. ionic fluxes,
      cell differentiation, and neuronal tissue regeneration, and also modulates
      programmed cell death. In this article, we review the experimental evidence
      supporting the notion that blockade of brain AT(1) receptors can be beneficial
      with respect to stroke incidence and outcome. We further delineate how AT(2)
      receptors could be involved in neuronal regeneration following brain injury such
      as stroke or CNS trauma. The current review is focussed on some of the new
      functions arising from the locally formed A-II with particular attention to its
      emerging neuroprotective role in the brain.

PMID- 15984908
TI  - Preventing cardiovascular outcome in patients with renal impairment: is there a
      role for lipid-lowering therapy?
AB  - Patients with chronic kidney disease (CKD), ranging from modest renal impairment
      to dialysis and transplant, have an increased risk for cardiovascular disease
      (CVD). Patients with CKD have both traditional and non-traditional risk factors
      for CVD. The role of lipids as risk factors for CVD in these populations has not
      been firmly established. In a recent prospective controlled trial, it was
      established that atherogenic lipids are indeed strong risk factors for CVD in
      renal transplant recipients, and that treatment with a HMG-CoA reductase
      inhibitor reduced the incidence of cardiac death and myocardial infarction. For
      patients receiving dialysis, the association between serum lipid levels and
      cardiovascular outcome is uncertain and there is no evidence from controlled
      trials that lipid-lowering therapy does have a beneficial effect on
      cardiovascular outcome in these patients. Atherogenic lipids are probably a risk
      factor for patients with mild or moderate CKD, and five subgroup analyses have
      indicated a favorable effect of lipid-lowering therapy on cardiovascular outcome,
      although we still lack prospective controlled trials in these patients. CVD in
      patients with CKD has been a neglected area of research.

PMID- 15984909
TI  - Effects of trimetazidine on myocardial perfusion and the contractile response of
      chronically dysfunctional myocardium in ischemic cardiomyopathy: a 24-month
      study.
AB  - OBJECTIVE: The aim was to assess the long-term effect of trimetazidine on
      myocardial perfusion, using gated single photon emission computerized tomography
      (SPECT). METHODS: 200 patients (aged 54.7 +/- 12 years) with ischemic left
      ventricular dysfunction (LVD) and multivessel coronary artery disease were
      randomized to receive trimetazidine 20mg three times daily or a placebo for 24
      months. At baseline and after 24 months of treatment, all patients underwent a
      symptom-limited cardiopulmonary exercise test concluded by the injection of
      (99m)Tc-MIBI (technetium-99m methoxy-isobutyl-isonitrile). Imaging of post-stress
      gated SPECT and resting gated SPECT were performed. Standard antianginal therapy
      was interrupted for 48 hours (nitrates for 6 hours) before the exercise tests and
      resumed immediately after testing. RESULTS: On initial evaluation, summed stress
      and rest scores (SSS and SRS, respectively), systolic wall thickness (SWT), and
      wall motion score index (WMI), heart rate, SBP, and rate pressure product were
      similar at rest and peak exercise in both groups. After 24 months, 91% of
      patients in the trimetazidine group versus 22% in the placebo group showed a
      significant decrease of the frequency of anginal episodes per week (3.9 vs 5.7, p
      < 0.01). Weekly nitroglycerin (glyceryl trinitrate) tablet consumption was
      significantly lower with trimetazidine than with placebo at endpoint (2.3 +/- 0.8
      vs 6.1 +/- 1.6, p < 0.01). This was supported by perfusion SPECT data. Compared
      with baseline values, SSS and SRS were significantly reduced with trimetazidine
      (from 19.8 +/- 7.7 to 11.2 +/- 6.1, p < 0.00001 and from 12.4 +/- 8.7 to 5.8 +/-
      3.3, p < 0.00001, respectively). There was a nonsignificant decrease from
      baseline values in both SRS and SSS with placebo group (from 11.9 +/- 8.3 to 11.2
      +/- 7.4 and 18.1 +/- 6.3 to 17.9 +/- 9.2, respectively). Duration of peak
      exercise increased significantly from baseline values with trimetazidine (from
      4.6 to 5.8 minutes, p < 0.01) but not with placebo (from 5.4 to 5.8 minutes).
      Accordingly, mean maximum work at peak exercise improved by 1.2 metabolic
      equivalents with trimetazidine. This was proved by gated SPECT with an increase
      in SWT score of 89.5% (p < 0.00001) and in ejection fraction of 23% with
      trimetazidine (p < 0.001) without significant changes in hemodynamic parameters.
      CONCLUSION: Trimetazidine improves ischemic attacks in patients with ischemic
      cardiomyopathy, clinically and objectively as seen in gated SPECT myocardial
      perfusion. The improvement in myocardial function with trimetazidine was not
      accompanied by hemodynamic changes.

PMID- 15984910
TI  - Agricultural antibiotics and human health.

PMID- 15984911
TI  - Population fitness and the regulation of Escherichia coli genes by bacterial
      viruses.
AB  - Temperate bacteriophage parasitize their host by integrating into the host genome
      where they provide additional genetic information that confers higher fitness on
      the host bacterium by protecting it against invasion by other bacteriophage, by
      increasing serum resistance, and by coding for toxins and adhesion factors that
      help the parasitized bacterium invade or evade its host. Here we ask if a
      temperate phage can also regulate host genes. We find several different host
      functions that are down-regulated in lysogens. The pckA gene, required for
      gluconeogenesis in all living systems, is regulated directly by the principal
      repressor of many different temperate prophage, the cI protein. cI binds to the
      regulatory region of pckA, thereby shutting down pckA transcription. The pckA
      regulatory region has target sequences for many other temperate phage repressors,
      and thus we suggest that down-regulation of the host pckA pathway increases
      lysogen fitness by lowering the growth rate of lysogens in energy-poor
      environments, perhaps as an adaptive response to the host predation system or as
      an aspect of lysogeny that must be offset by down-regulating pckA.

PMID- 15984914
TI  - Sleep and risk-taking behavior in adolescents.
AB  - The primary purpose of this study was to examine the relationship between
      adolescents' sleep-wake patterns and risk-taking behavior. A second goal was to
      replicate the results obtained by Wolfson and Carskadon (1998) regarding
      adolescents' sleep habits. Three hundred eighty-eight adolescents (217 males, 171
      females) completed the Sleep Habits Survey and the Youth Risk Behavior Survey.
      The results indicated that adolescents who reported longer weekend delay and
      higher levels of sleep problems also reported significantly higher levels of risk
      taking behaviors, and students' weekend delay was also related to their academic
      performance in this sample. As in the sample studied by Wolfson and Carskadon
      (1998), the adolescents in this study exhibited changes in both weekday and
      weekend sleep habits across grade/age. However in the present study, only school
      night total sleep time and weekend delay were related to adolescents' daytime
      functioning, with no significant relationships being found between weekend
      oversleep and daytime functioning. This provides partial support for the findings
      of Wolfson and Carskadon (1998). Overall, sleep-wake patterns were found to
      relate to risk-taking behavior during adolescence in this study.

PMID- 15984913
TI  - The genome sequence of Rickettsia felis identifies the first putative conjugative
      plasmid in an obligate intracellular parasite.
AB  - We sequenced the genome of Rickettsia felis, a flea-associated obligate
      intracellular alpha-proteobacterium causing spotted fever in humans. Besides a
      circular chromosome of 1,485,148 bp, R. felis exhibits the first putative
      conjugative plasmid identified among obligate intracellular bacteria. This
      plasmid is found in a short (39,263 bp) and a long (62,829 bp) form. R. felis
      contrasts with previously sequenced Rickettsia in terms of many other features,
      including a number of transposases, several chromosomal toxin-antitoxin genes,
      many more spoT genes, and a very large number of ankyrin- and tetratricopeptide
      motif-containing genes. Host-invasion-related genes for patatin and RickA were
      found. Several phenotypes predicted from genome analysis were experimentally
      tested: conjugative pili and mating were observed, as well as beta-lactamase
      activity, actin-polymerization-driven mobility, and hemolytic properties. Our
      study demonstrates that complete genome sequencing is the fastest approach to
      reveal phenotypic characters of recently cultured obligate intracellular
      bacteria.

PMID- 15984915
TI  - Time estimation ability and distorted perception of sleep in insomnia.
AB  - Although it is an established finding that people with insomnia
      characteristically overestimate the time they have taken to get to sleep and
      underestimate the total amount of time they have slept, little is known about the
      mechanisms that underpin this phenomenon. Accordingly, this study sought to
      investigate whether the tendency to misperceive sleep among patients with
      insomnia is accounted for by (a) a general deficit in time estimation ability or
      (b) the context in which the time estimates are made. Twenty individuals with
      insomnia and 20 individuals who did not have insomnia were asked to perform two
      time estimation tasks; one in the laboratory during the day and one in the
      participant's own bedroom during the night. The two groups were compared with
      respect to the accuracy of their performance in estimating unfilled temporal
      intervals of various lengths. The results indicated that the performance of the
      insomnia group was no different from that of the noninsomnia group, regardless of
      the context in which the time estimates were made. Time overestimation correlated
      positively with cognitive and physiological arousal experienced during the time
      estimation tasks. These findings argue against the hypothesis that individuals
      with insomnia misperceive their sleep simply because they are poor estimators of
      time. Future research is required to test the hypothesis that increased cognitive
      arousal (worry) and physiological arousal are candidate mechanisms that underpin
      sleep misperception.

PMID- 15984916
TI  - Case series utilizing exposure, relaxation, and rescripting therapy: impact on
      nightmares, sleep quality, and psychological distress.
AB  - Experiencing a traumatic event may initiate or exacerbate the occurrence of
      nightmares. Nightmares may impact sleep quality and quantity, posttraumatic
      stress symptoms, and depression. Recently, imagery rehearsal has gained attention
      in the treatment of trauma-related nightmares and is reported to be promising in
      the reduction of nightmares. On the basis of the vast literature describing the
      therapeutic benefits of exposure techniques for anxiety-related problems, the
      treatment was modified to enhance the exposure component. This article presents a
      case series using this modified version of imagery rehearsal, Exposure,
      Relaxation, and Rescripting Therapy, with 1 male and 3 female participants.
      Overall, the participants treated reported a reduction in nightmare frequency and
      severity; 3 out of 4 participants also reported a reduction in posttraumatic
      stress and depression symptomotology and an increase in sleep quality and
      quantity. Clinical implications and future research directions are discussed.

PMID- 15984917
TI  - Home-based video CBT for comorbid geriatric insomnia: a pilot study using
      secondary data analyses.
AB  - Two recent studies showed that cognitive-behavioral treatment (CBT) is
      efficacious in treating insomnia in older adults with comorbid medical
      conditions. The authors extended these findings by comparing 12 older adults with
      comorbid insomnia who received a home-based video CBT program to the authors'
      previously published data on 24 participants who received classroom CBT or no
      treatment. All 36 participants were initially randomized within the same
      protocol, but the video arm was conducted 7 months after completion of the other
      two study arms. Compared to controls, the video CBT group demonstrated
      significant changes in five of eight self-report measures of sleep at
      posttreatment, including sleep latency, time awake after sleep onset, total time
      in bed, overall sleep quality, and dysfunctional beliefs and attitudes about
      sleep. Compared to controls, the video CBT group also had posttreatment
      improvements in daytime functioning, including mood, pain perception, social
      functioning, and energy-vitality. Although video CBT was not significantly
      different from classroom CBT on self-report measures, the attrition rate was
      higher (27% vs. 19%) and the number of participants who achieved clinically
      significant change was lower (50% vs. 73%). These preliminary findings suggest
      that delivering CBT in a home-based video format has the potential to serve as a
      first-line, cost-effective treatment for comorbid insomnia.

PMID- 15984929
TI  - Desferrioxamine release from gelatin-based systems.
AB  - The conventional treatment with regular red-blood-cell transfusions and
      simultaneous chelation of excess iron with DFO (desferrioxamine) improves quality
      of life of thalassaemic patients while increasing their rate of survival
      considerably. Although DFO is the main iron- chelating drug currently utilized,
      it has various drawbacks, including high cost, poor oral effectiveness, toxicity
      and short plasma half-life. It has to be administered by slow, subcutaneous
      infusion during blood transfusion for 8-12 h at night, 5-7 nights a week, and
      this leads to a very poor patient compliance. In order to avoid frequent and
      uncomfortable infusions of DFO, application of controlled-release systems might
      be alternative routes in the supportive treatment of thalassaemia. In the present
      study, GMs (gelatin microspheres) and GFs (gelatin films) were prepared by
      coacervation and casting methods respectively to develop controlled DFO-release
      systems. Cross-linking by glutaraldehyde and carbodi-imide were performed to
      increase the stability of gelatin matrices. Microspheres and films prepared
      without the addition of cross-linker degraded completely in 4 h. On the other
      hand, addition of cross-linker extended this time from hours to weeks depending
      on the added amount. Therefore the amount of DFO released from microspheres in 7
      days was found to be in the range 12-82%, whereas the amount permeated through
      the films in 5.0 h was found to be in the range 34-67%. GFs were elastic and
      demonstrated good mechanical properties. Films achieved 0.14-0.69 MPa tensile
      strength, with 0.12-1.29 MPa elastic modulus and 26.49-109.38% strain values at
      break point. These studies showed that gelatin-based controlled-release systems
      could be improved and could be good candidates for the production of long-term
      DFO-carrying systems.

PMID- 15984930
TI  - Functional analysis of the promoter of the mitochondrial phosphate carrier human
      gene: identification of activator and repressor elements and their transcription
      factors.
AB  - The phosphate carrier (PiC) catalyses the import of phosphate into mitochondria
      where it is needed for ATP synthesis. We have analysed the 5'-flanking region of
      the human PiC gene and found that it has a single transcriptional initiation site
      and lacks a TATA box. Through deletion analysis of the -1213/-25 nt region, we
      identified an activation domain (-223/-25) and an inhibition domain (-1017/-814).
      The most effective promoter activity in transfected HeLa cells corresponded to
      the region containing putative binding sites for Sp1 (-163/-142; where Sp1 stands
      for stimulating protein-1) and CREB (-138/-116; where CREB stands for cAMP
      response-element-binding protein). These DNA sequences were active in gel-shift
      assays in the presence of HeLa cell nuclear extracts or recombinant Sp1 and CREB
      respectively. Forskolin increased PiC promoter activity via the CREB site. Both
      footprinting and transfection of deletion constructs of the inhibition region (
      1017/-814) showed that PiC silencer activity extends over 25 nt (-943/-919),
      which specifically binds two proteins present in HeLa cell nuclear extracts.
      These transcription factors were purified by DNA affinity, analysed by MS and
      identified as p54(nrb)/NonO (nuclear RNA binding protein) and PSF (protein
      associated splicing factor). The PiC silencer region cloned in front of the
      ferritin promoter conferred a strong inhibition to the heterologous promoter.
      These findings may provide insight into control of PiC gene expression in
      different cell types and under different growth conditions. To our knowledge,
      this is the first study to analyse the regulation of the PiC gene expression in
      any cell.

PMID- 15984912
TI  - Traces of archaic mitochondrial lineages persist in Austronesian-speaking
      Formosan populations.
AB  - Genetic affinities between aboriginal Taiwanese and populations from Oceania and
      Southeast Asia have previously been explored through analyses of mitochondrial
      DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic
      studies have supported the "slow boat" and "entangled bank" models according to
      which the Polynesian migration can be seen as an expansion from Melanesia without
      any major direct genetic thread leading back to its initiation from Taiwan. We
      assessed mtDNA variation in 640 individuals from nine tribes of the central
      mountain ranges and east coast regions of Taiwan. In contrast to the Han
      populations, the tribes showed a low frequency of haplogroups D4 and G, and an
      absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal
      lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although
      indicating a common origin of the populations of insular Southeast Asia and
      Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped
      separately from those found in China and the Taiwan general (Han) population,
      suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late
      Pleistocene settlers. Interestingly, from complete mtDNA sequencing information,
      most B4a lineages were associated with three coding region substitutions,
      defining a new subclade, B4a1a, that endorses the origin of Polynesian migration
      from Taiwan. Coalescence times of B4a1a were 13.2 +/- 3.8 thousand years (or 9.3
      +/- 2.5 thousand years in Papuans and Polynesians). Considering the lack of a
      common specific Y chromosomal element shared by the Taiwanese aboriginals and
      Polynesians, the mtDNA evidence provided here is also consistent with the
      suggestion that the proto-Oceanic societies would have been mainly matrilocal.

PMID- 15984931
TI  - Identification, molecular cloning and functional characterization of an
      octaprenyl pyrophosphate synthase in intra-erythrocytic stages of Plasmodium
      falciparum.
AB  - Isoprenoids play important roles in all living organisms as components of
      structural cholesterol, steroid hormones in mammals, carotenoids in plants, and
      ubiquinones. Significant differences occur in the length of the isoprenic side
      chains of ubiquinone between different organisms, suggesting that different
      enzymes are involved in the synthesis of these side chains. Whereas in Plasmodium
      falciparum the isoprenic side chains of ubiquinone contain 7-9 isoprenic units,
      10-unit side chains are found in humans. In a search for the P. falciparum enzyme
      responsible for the biosynthesis of isoprenic side chains attached to the
      benzoquinone ring of ubiquinones, we cloned and expressed a putative polyprenyl
      synthase. Polyclonal antibodies raised against the corresponding recombinant
      protein confirmed the presence of the native protein in trophozoite and schizont
      stages of P. falciparum. The recombinant protein, as well as P. falciparum
      extracts, showed an octaprenyl pyrophosphate synthase activity, with the
      formation of a polyisoprenoid with eight isoprenic units, as detected by reverse
      phase HPLC and reverse-phase TLC, and confirmed by electrospray ionization and
      tandem MS analysis. The recombinant and native versions of the enzyme had similar
      Michaelis constants with the substrates isopentenyl pyrophosphate and farnesyl
      pyrophosphate. The recombinant enzyme could be competitively inhibited in the
      presence of the terpene nerolidol. This is the first report that directly
      demonstrates an octaprenyl pyrophosphate synthase activity in parasitic protozoa.
      Given the rather low similarity of the P. falciparum enzyme to its human
      counterpart, decaprenyl pyrophosphate synthase, we suggest that the identified
      enzyme and its recombinant version could be exploited in the screening of novel
      drugs.

PMID- 15984932
TI  - Liver fatty-acid-binding protein (L-FABP) gene ablation alters liver bile acid
      metabolism in male mice.
AB  - Although the physiological roles of the individual bile acid synthetic enzymes
      have been extensively examined, relatively little is known regarding the function
      of intracellular bile acid-binding proteins. Male L-FABP (liver fatty-acid
      binding protein) gene-ablated mice were used to determine a role for L-FABP, the
      major liver bile acid-binding protein, in bile acid and biliary cholesterol
      metabolism. First, in control-fed mice L-FABP gene ablation alone increased the
      total bile acid pool size by 1.5-fold, especially in gall-bladder and liver, but
      without altering the proportions of bile acid, cholesterol and phospholipid. Loss
      of liver L-FABP was more than compensated by up-regulation of: other liver
      cytosolic bile acid-binding proteins [GST (glutathione S-transferase), 3alpha-HSD
      (3alpha-hydroxysteroid dehydrogenase)], key hepatic bile acid synthetic enzymes
      [CYP7A1 (cholesterol 7alpha-hydroxylase) and CYP27A1 (sterol 27alpha
      hydroxylase)], membrane bile acid translocases [canalicular BSEP (bile salt
      export pump), canalicular MRP2 (multidrug resistance associated protein 2), and
      basolateral/serosal OATP-1 (organic anion transporting polypeptide 1)], and
      positive alterations in nuclear receptors [more LXRalpha (liver X receptor alpha)
      and less SHP (short heterodimer partner)]. Secondly, L-FABP gene ablation
      reversed the cholesterol-responsiveness of bile acid metabolic parameters such
      that total bile acid pool size, especially in gall-bladder and liver, was reduced
      4-fold, while the mass of biliary cholesterol increased 1.9-fold. The
      dramatically reduced bile acid levels in cholesterol-fed male L-FABP (-/-) mice
      were associated with reduced expression of: (i) liver cytosolic bile acid-binding
      proteins (L-FABP, GST and 3alpha-HSD), (ii) hepatic bile acid synthetic enzymes
      [CYP7A1, CYP27A1 and SCP-x (sterol carrier protein-x/3-ketoacyl-CoA thiolase)]
      concomitant with decreased positive nuclear receptor alterations (i.e. less
      LXRalpha and more SHP), and (iii) membrane bile acid transporters (BSEP, MRP2 and
      OATP-1). These are the first results suggesting a physiological role for the
      major cytosolic bile acid-binding protein (L-FABP) in influencing liver bile
      metabolic phenotype and gall-bladder bile lipids of male mice, especially in
      response to dietary cholesterol.

PMID- 15984933
TI  - Alternatively spliced human genes by exon skipping--a database (ASHESdb).
AB  - Alternative splicing of mRNA allows many gene products with different functions
      to be produced from a single coding sequence. Exon skipping is the most commonly
      known alternative splicing mechanism. A comprehensive database of alternative
      splicing by exon skipping is made available for the human genome data. 1,229
      human genes are identified to exhibit alternative splicing by exon skipping.
      AVAILABILITY: http://sege.ntu.edu.sg/wester/ashes/.

PMID- 15984934
TI  - SPI--structure predictability index for protein sequences.
AB  - Estimation of structure predictability for a particular protein is difficult.
      Many methods estimate it in an a posteriori system evaluating the final, native
      protein structure. The SPI scale is intended to estimate the structure
      predictability of a particular amino acid sequence in an a priori system. A
      sequence-to-structure library was created based on the complete Protein Data
      Bank. The tetrapeptide was selected as a unit representing a well-defined
      structural motif. The early-stage folding structure (a model of which was
      presented elsewhere) was taken as the object for protein structure
      classification. Seven structural forms were distinguished for structure
      classification. The degree of determinability was estimated for the sequence-to
      structure and structure-to-sequence relations particularly interesting for
      threading methods. A comparative analysis of the SPI and Q7 scales with the
      commonly used SOV and Q3 scales is presented. The complete contingency table,
      supplementary materials and all the programs used are available on request.

PMID- 15984935
TI  - Simulations of simple artificial genetic networks reveal features in the use of
      Relevance Networks.
AB  - Recent research on large scale microarray analysis has explored the use of
      Relevance Networks to find networks of genes that are associated to each other in
      gene expression data. In this work, we compare Relevance Networks with other
      types of clustering methods to test some of the stated advantages of this method.
      The dataset we used consists of artificial time series of Boolean gene expression
      values, with the aim of mimicking microarray data, generated from simple
      artificial genetic networks. By using this dataset, we could not confirm that
      Relevance Networks based on mutual information perform better than Relevance
      Networks based on Pearson correlation, partitional clustering or hierarchical
      clustering, since the results from all methods were very similar. However, all
      three methods successfully revealed the subsets of co-expressed genes, which is a
      valuable step in identifying co-regulation.

PMID- 15984937
TI  - Four basic symmetry types in the universal 7-cluster structure of microbial
      genomic sequences.
AB  - Coding information is the main source of heterogeneity (non-randomness) in the
      sequences of microbial genomes. The heterogeneity corresponds to a cluster
      structure in triplet distributions of relatively short genomic fragments (200-400
      bp). We found a universal 7-cluster structure in microbial genomic sequences and
      explained its properties. We show that codon usage of bacterial genomes is a
      multi-linear function of their genomic G+C-content with high accuracy. Based on
      the analysis of 143 completely sequenced bacterial genomes available in Genbank
      in August 2004, we show that there are four "pure" types of the 7-cluster
      structure observed. All 143 cluster animated 3D-scatters are collected in a
      database which is made available on our web-site
      (http://www.ihes.fr/~zinovyev/7clusters). The findings can be readily introduced
      into software for gene prediction, sequence alignment or microbial genomes
      classification.

PMID- 15984936
TI  - Magmas gene structure and evolution.
AB  - Magmas is a nuclear encoded protein found in the mitochondria of mammalian cells.
      It participates in granulocyte-macrophage-colony stimulating factor (GM-CSF)
      signaling in hematopoietic cells and has an essential role in invertebrate
      development. In order to characterize the protein structural features and gene
      evolution of Magmas, a dataset containing 61 Magmas homologs from 52 species
      distributed among animals, plants and fungi was analyzed. All Magmas members were
      found to possess three novel sequence motifs in addition to a conserved leader
      peptide. Phylogenetic tree and dN/dS rate ratios showed that Magmas was
      evolutionarily conserved. Analysis of Magmas gene organization demonstrated
      incremental intron acquisition in plants and vertebrates. Significant genetic
      diversity in Magmas was observed from kingdom specific amino acid signatures, the
      presence of predicted signal peptides that target the protein to other
      intracellular locations besides the mitochondria, and the detection of multiple
      isoforms in higher animals. These studies demonstrate that Magmas members
      constitute an important family of conserved proteins having multifunctional
      activities, and provide a basis for future experiments.

PMID- 15984938
TI  - Collection of soluble variants of membrane proteins for transcriptomics and
      proteomics.
AB  - The existence of a soluble splice variant for a gene encoding a transmembrane
      protein suggests that this gene plays a role in intercellular signalling,
      particularly in immunological processes. Also, the absence of a splice variant of
      a reported soluble variant suggests exclusive control of the solubilisation by
      proteolytic cleavage. Soluble splice variants of membrane proteins may also be
      interesting targets for crystallisation as their structure may be expected to
      preserve, at least partially, their function as integral membrane proteins, whose
      structures are most difficult to determine. This paper presents a dataset derived
      from the literature in an attempt to collect all reported soluble variants of
      membrane proteins, be they splice variants or shedded. A list of soluble variants
      is derived in silico from Ensembl. These are checked on their presence in
      multiple organisms and their number of membranespanning regions is inspected. The
      findings then are confirmed by a comparison with identified proteins of a recent
      global proteomics study of human blood plasma. Finally, a tool to determine novel
      soluble variants by proteomics is provided.

PMID- 15984939
TI  - Nomenclature-based data retrieval without prior annotation: facilitating
      biomedical data integration with fast doublet matching.
AB  - Assigning nomenclature codes to biomedical data is an arduous, expensive and
      error-prone task. Data records are coded to to provide a common representation of
      contained concepts, allowing facile retrieval of records via a standard
      terminology. In the medical field, cancer registrars, nurses, pathologists, and
      private clinicians all understand the importance of annotating medical records
      with vocabularies that codify the names of diseases, procedures, billing
      categories, etc. Molecular biologists need codified medical records so that they
      can discover or validate relationships between experimental data and clinical
      data. This paper introduces a new approach to retrieving data records without
      prior coding. The approach achieves the same result as a search over pre-coded
      records. It retrieves all records that contain any terms that are synonymous with
      a user's query-term. A recently described fast algorithm (the doublet method)
      permits quick iterative searches over every synonym for any term from any
      nomenclature occurring in a dataset of any size. As a demonstration, a 105+
      Megabyte corpus of Pubmed abstracts was searched for medical terms. Query terms
      were matched against either of two vocabularies and expanded as an array of
      equivalent search items. A single search term may have over one hundred
      nomenclature synonyms, all of which were searched against the full database.
      Iterative searches of a list of concept-equivalent terms involves many more
      operations than a single search over pre-annotated concept codes. Nonetheless,
      the doublet method achieved fast query response times (0.05 seconds using Snomed
      and 5 seconds using the Developmental Lineage Classification of Neoplasms, on a
      computer with a 2.89 GHz processor). Pre-annotated datasets lose their value when
      the chosen vocabulary is replaced by a different vocabulary or by a different
      version of the same vocabulary. The doublet method can employ any version of any
      vocabulary with no pre-annotation. In many instances, the enormous effort and
      expense associated with data annotation can be eliminated by on-the-fly doublet
      matching. The algorithm for nomenclature-based database searches using the
      doublet method is described. Perl scripts for implementing the algorithm and
      testing execution speed are provided as open source documents available from the
      Association for Pathology Informatics
      (www.pathologyinformatics.org/informatics_r.htm).

PMID- 15984940
TI  - Evolutionary analysis of human vascular endothelial growth factor, angiopoietin,
      and tyrosine endothelial kinase involved in angiogenesis and immunity.
AB  - Human vascular endothelial growth factor (VEGF), angiopoietin (ANG) and tyrosine
      kinase with immunoglobulin and epidermal growth factor homology domains (TIE)-2
      consist of a grouping of proteins that are involved in vascular homeostasis,
      vascular integrity and angiogenesis. There are nine proteins in the immediate
      VEGF family: VEGFA, VEGFB, VEGFC, VEGFD, VEGF-3, placental growth factor (PGF),
      VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-1-related. They can be stimulated by
      cytokines to become involved in immune responses. By using in silico tools, we
      were able to identify several possible analogues or homologues of VEGF, ANG and
      TIE-2 in invertebrates. This is the first report to show that these proteins may
      be conserved through evolution. These proteins may have a role in vascular
      maintenance and immunity. In addition, since VEGF, ANG and TIE-2 have a role in
      mammalian immunity that is significantly influenced by cytokines, such as IL-1,
      this may indicate an interaction of the vascular system and the immune system
      over evolutionary time.

PMID- 15984941
TI  - Cryptococcosis after solid organ transplantation.

PMID- 15984942
TI  - Active Epstein-Barr virus infection after allogeneic stem cell transplantation:
      re-infection or reactivation?
AB  - Recipients of allogeneic stem cell transplants (SCT) often show active Epstein
      Barr virus (EBV) infection, which may progress to EBV-associated
      lymphoproliferative disorders. It is not known whether these EBV infections are
      true reactivations of the endogenous EBV strain or re-infections with an
      exogenous EBV strain. Fifty-three recipients of matched related or matched
      unrelated donor grafts were studied. EBV monitoring was based on a realtime
      TaqMan EBV DNA polymerase chain reaction (PCR) assay in plasma. In 17 patients,
      EBV DNA PCR monitoring was performed in peripheral blood mononuclear cells
      (PBMCs) as well. Mouth washings (MWs) were collected pre-transplant from all
      patients and family donors. Both pre-transplant EBV DNA from MWs and post
      transplant EBV DNA from plasma or PBMCs were successfully obtained in 6 patients.
      A nested PCR targeting the EBV latent membrane protein-1 C-terminus gene was used
      to determine sequence variations enabling EBV strain typing. In 3 of 6 patients,
      the post-transplant EBV sequence pattern differed from the pre-transplant
      pattern, indicating a re-infection post-transplant with an exogenous strain
      instead of a reactivation of the original endogenous EBV strain. In the other 3
      patients, the endogenous strain was identified. Active EBV infection resulting
      from re-infection was more severe compared with active EBV infection because of
      reactivation. In conclusion, active EBV infections after allogeneic SCT
      frequently result from re-infection with an exogenous EBV strain instead of a
      true reactivation of the endogenous strain and are potentially more severe.

PMID- 15984943
TI  - Pre- and post-engraftment bloodstream infection rates and associated mortality in
      allogeneic hematopoietic stem cell transplant recipients.
AB  - We report on bloodstream infection (BSI) rates, risk factors, and outcome in a
      cohort of 298 adult and pediatric hematopoietic stem cell transplantation (HSCT)
      recipients at Memorial Sloan-Kettering Hospital from September 1999 through June
      2003. Methods. Prospective surveillance study. BSI rates are reported per 10,000
      HSCT days. Date of engraftment is defined as the first of at least 3 consecutive
      dates of absolute neutrophil count >500/mm(3) after stem cell infusion. BSI
      severity grades: severe (intravenous antibiotics), life threatening (sepsis), or
      fatal (caused or contributed to death). Results. The incidence of pre- and post
      engraftment BSI was 22% and 19.5%, respectively. Pre-engraftment highest rates
      were observed for viridans streptococci (58), Enterobacteriaceae (39), and
      Enterococcus faecium (34). Post-engraftment rates ranged from 0.2 to 2.9 without
      any predominant pathogen. In multivariate analyses, pre-engraftment BSI was
      associated with diagnosis of chronic myelogenous leukemia, age >18 years and
      peripheral blood stem cell graft; post-engraftment BSI was associated with acute
      graft-versus-host disease, neutropenia, and liver or kidney dysfunction.
      Attributable mortality was 12.5% and 1.7% for pre- and post-engraftment BSI,
      respectively. BSI fatality rates were 24% for viridans streptococci, 8% for E.
      faecium, 11% for Staphylococcus aureus, and 67% for Candida. Conclusions. Pre
      engraftment BSI, especially by viridans streptococci and E. faecium, was
      associated with substantial attributable mortality. Post-engraftment BSI was a
      marker of post-transplant complications and rarely the primary cause of death.

PMID- 15984944
TI  - A renal transplant recipient with pulmonary nodules.

PMID- 15984945
TI  - Cryptococcosis after living donor liver transplantation: report of three cases.
AB  - Cryptococcosis is the third most common invasive fungal infection in solid organ
      transplantation, which usually occurs more than 6 months after the primary
      operation. In our series of 180 consecutive adult living-donor liver
      transplantation recipients, three (1.5%) had cryptococcosis and one of these
      patients died. The serum cryptococcal antigen examination was positive in all
      three patients who suffered from cryptococcosis. The serum cryptococcal antigen
      test might contribute to the early detection and treatment of cryptococcosis.

PMID- 15984946
TI  - Long-term remission of recurrent parvovirus-B associated anemia in a renal
      transplant recipient induced by treatment with immunoglobulin and positive
      seroconversion.
AB  - Parvovirus B-19 (PVB)-related recurrent anemia is reported in a renal transplant
      recipient with long-term remission induced by intravenous immunoglobulin and
      decreasing immunosuppression. Positive plasma polymerase chain reaction (PCR) and
      intense bone marrow infection were present at diagnosis, despite the absence of
      serum immunoglobulin IgG and IgM antibodies to the virus. Seroconversion against
      the virus was followed by long-term remission while the plasma PCR for PVB
      remained positive. This case illustrates the absence of serum antibodies in an
      immunosuppressed host despite florid infection with the virus. Positive
      seroconversion in a naive subject is associated with long-term remission even in
      the presence of detectable viral DNA copies in the plasma.

PMID- 15984948
TI  - Disseminated toxoplasmosis with pulmonary involvement after heart
      transplantation.
AB  - We report a case of pulmonary toxoplasmosis after heart transplant despite the
      prophylactic anti-toxoplasmic treatment that was given but was not sufficient to
      prevent toxoplasmosis. However, the patient survived thanks to early diagnosis
      confirmed by polymerase chain reaction on blood and by serological techniques,
      and early treatment.

PMID- 15984947
TI  - Human herpesvirus-8-related Kaposi's sarcoma after liver transplantation
      successfully treated with cidofovir and liposomal daunorubicin.
AB  - The iatrogenic form of Kaposi's sarcoma (KS) is typically observed among
      transplant recipients, and the most appropriate therapeutic approach (usually
      including reduction of immunosuppression, specific chemotherapy, and/or
      administration of antiviral agents against human herpes virus-8) is still
      controversial. Available experiences on the effect of the anti-herpes viruses
      drug cidofovir provide conflicting results. Herein, we report the clinical,
      histological, and virological features of a liver transplant recipient
      successfully treated with a combined therapy of cidofovir and liposomal
      daunorubicin, associated with a reduction of the immunosuppressive regimen, for
      an advanced cutaneous and visceral KS.

PMID- 15984949
TI  - Severe hypogammaglobulinemia associated with hepatic vein stenosis causes
      cytomegalovirus infection after living-related liver transplantation.
AB  - Hepatic vein stenosis is a vascular complication that can lead to graft loss
      after liver transplantation. Although ascites frequently occurs as a symptom of
      hepatic vein stenosis, the development of severe hypogammaglobulinemia associated
      with hepatic vein stenosis has not been reported in the literature. An 8-year-old
      boy underwent living-related liver transplantation (LRLT) because of Wilson
      disease with chronic hepatic failure. Because de novo autoimmune hepatitis was
      diagnosed 1 year after LRLT, azathioprine, and prednisolone were added to the
      baseline immunosuppression of tacrolimus. The patient developed ascites with
      severe hypogammaglobulinemia (immunoglobulin G [IgG], 288 mg/dL) 2 years after
      LRLT. Ultrasonography and angiography disclosed stenosis of the hepatic vein. The
      ascites completely resolved after percutaneous balloon angioplasty. Despite serum
      IgG trough levels of >500 mg/dL maintained by the addition of immunoglobulin,
      cytomegalovirus reactivation and sepsis occurred. Serum IgG levels should be
      monitored to prevent opportunistic infections when hepatic vein stenosis is
      diagnosed after LRLT.

PMID- 15984950
TI  - Multidrug-resistant tuberculosis in bone marrow transplant recipient.
AB  - Multidrug-resistant tuberculosis (TB) is an increasing problem worldwide, however
      only three cases have been previously described in transplant recipients,
      especially involving lung and heart transplant. We describe a case of multidrug
      resistant TB in an allogenic bone marrow transplant recipient with good response
      to second-line therapy.

PMID- 15984951
TI  - Are your patients at risk? Fungal contamination of Ilex paraguariensis St. Hil
      (yerba mate).

PMID- 15984952
TI  - Mucosal disease series. Number III. Mucous membrane pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It
      is now quite evident that a number of sub-epithelial vesiculobullous disorders
      may produce similar clinical pictures, and also that a range of variants of MMP
      exist, with antibodies directed against various hemidesmosomal components or
      components of the epithelial basement membrane. The term immune-mediated sub
      epithelial blistering diseases (IMSEBD) has therefore been used. Immunological
      differences may account for the significant differences in their clinical
      presentation and responses to therapy, but unfortunately data on this are few.
      The diagnosis and management of IMSEBD on clinical grounds alone is impossible
      and a full history, general, and oral examination, and biopsy with immunostaining
      are now invariably required, sometimes supplemented with other investigations. No
      single treatment regimen reliably controls all these disorders, and it is not
      known if the specific subsets of MMP will respond to different drugs. Currently,
      apart from improving oral hygiene, immunomodulatory-especially immunosuppressive
      therapy is typically used to control oral lesions. The present paper reviews
      pemphigoid, describing the present understanding of this fascinating clinical
      phenotype, summarising the increasing number of subsets with sometimes-different
      natural histories and immunological features, and outlining current clinical
      practice.

PMID- 15984953
TI  - Viruses in periodontal disease - a review.
AB  - The purpose of this review was to evaluate the evidence supporting the hypothesis
      that viral infection plays a role in the development of periodontitis. An
      involvement in periodontal diseases has been suspected specifically for human
      immunodeficiency virus (HIV) and herpes viruses. An association has been
      demonstrated between HIV infection and some distinct forms of periodontal
      infection, i.e. necrotizing lesions. Furthermore, reports of increased prevalence
      and severity of chronic periodontitis in HIV-positive subjects suggests that HIV
      infection predispose to chronic periodontitis. Several studies, most of them from
      the same research group, have demonstrated an association of herpesviruses with
      periodontal disease. Viral DNA have been detected in gingival tissue, gingival
      cervicular fluid (GCF) and subgingival plaque from periodontaly diseased sites.
      In addition markers of herpesviral activation have been demonstrated in the GCF
      from periodontal lesions. Active human cytomegalovirus (HCMV) replication in
      periodontal sites may suggest that HCMV re-activation triggers periodontal
      disease activity. Concerns regarding sampling, methods and interpretation cast
      doubts on the role of viruses as causes of periodontal disease.

PMID- 15984954
TI  - Transmission of hepatitis C virus by saliva?
AB  - Saliva can contain a range of infectious agents and, despite several
      antimicrobial mechanisms, transmission of these can occur. Hepatitis C virus
      (HCV) is of increasing importance, and HCV is transmitted by unknown routes as
      well as by the percutaneous route and sexual contact. Contact with blood or other
      body fluids may be responsible, as may be receipt of unscreened blood or blood
      product transfusions. HCV-RNA can be detected by the polymerase chain reaction
      which also shows that HCV may be present in the saliva of HCV-infected patients.
      This might provide an argument for the possible transmission of HCV via
      contaminated saliva. Epidemiological studies however, suggest that the infective
      capacity of HCV viral particles in saliva is low, but it has not been possible to
      determine their infective potential. Moreover, HCV-specific receptors have not
      been defined on oral epithelial cells, nor has the role of host defence
      mechanisms been determined. New experimental animal models and the recently
      described infectious HCV pseudoparticles, capable of simulating HCV replication
      in vitro, could be useful in establishing any role of saliva in the transmission
      of HCV infection.

PMID- 15984955
TI  - Relationship between intracellular ROS production and membrane mobility in
      curcumin- and tetrahydrocurcumin-treated human gingival fibroblasts and human
      submandibular gland carcinoma cells.
AB  - OBJECTIVE: Curcumin is a well-known chemopreventive agent of oral cancers as well
      as stomach and intestinal cancers. The relationship between reactive oxygen
      species (ROS) production and cell membrane mobility was investigated to clarify
      the pro-oxidant mechanism of curcumin and tetrahydrocurcumin (TH-curcumin).
      METHODS: The intracellular ROS production and membrane mobility by curcumin or TH
      curcumin were measured in human submandibular adenocarcinoma cells (HSGs) and
      human primary gingival fibroblasts (HGFs). ROS and mobility were measured by 5
      (and -6)-carboxy-2',7'-dichlorofluorescein diacetate staining and fluorescence
      recovery after photo bleaching, respectively. RESULTS: Curcumin produced ROS dose
      dependently. ROS appeared in the region surrounding the cell membrane. The
      membrane mobility coefficient of the curcumin-treated cells was significantly
      lower than that of control cells. The lowered membrane mobility induced by
      curcumin was reversed by the addition of glutathione, an antioxidant. In
      contrast, TH-curcumin did not affect the ROS production or the membrane mobility
      coefficient. The alternations induced by curcumin treated HSG cells were greater
      than those by HGF cells. CONCLUSION: The reduction in membrane mobility induced
      by curcumin was attributed to ROS production. The oxidative effects of curcumin
      may be related to the structure of the alpha, beta-unsaturated carbonyl moiety as
      well as the phenolic OH group of this compound.

PMID- 15984956
TI  - Haemostatic management of intraoral bleeding in patients with von Willebrand
      disease.
AB  - OBJECTIVES: To develop plans for the haemostatic management of intraoral bleeding
      in patients with von Willebrand disease (VWD). SUBJECTS AND METHODS: Thirty-seven
      episodes of haemostatic management of intraoral bleeding in 19 VWD patients were
      analysed retrospectively based on the medical records. RESULTS AND CONCLUSIONS:
      When performing tooth extractions in patients with type 1 or 2A VWD [responsive
      to 1-deamino-8-D-arginine-vasopressin (DDAVP)], 0.35-0.4 microg kg(-1) of DDAVP
      should be administered intravenously at three times. In patients with type 2A VWD
      (unresponsive to DDAVP) or patients with type 2B or 2N VWD, 50-90 U [as
      ristocetin cofactor (VWF:RCof)] kg(-1) of a factor VIII concentrate containing
      von Willebrand factor (FVIII/VWF concentrate) should be administered twice in
      routine extractions, and four to six times in surgical extractions. Gingival
      bleeding related to primary teeth can be mostly managed by pressure haemostasis
      alone. However, when treating gingival bleeding caused by marginal periodontitis,
      it is often necessary to administer 0.4 microg kg(-1) of DDAVP or 40-70 U (as
      VWF:RCof) kg(-1) of a FVIII/VWF concentrate. As local haemostasis is difficult to
      achieve in bleeding from the tongue or labial or mandibular haematoma, it is
      necessary to administer 0.4 microg kg(-1) of DDAVP or 60-80 U (as VWF:RCof) kg(
      1) of a FVIII/VWF concentrate. In addition, oral administration of 20 mg kg(-1)
      day(-1) of tranexamic acid should be combined with the regimens described above.

PMID- 15984957
TI  - Quantification of mast cells in different stages of human periodontal disease.
AB  - OBJECTIVE AND METHODS: Among the cells involved in immune and inflammatory
      responses in periodontal disease, mast cells have been shown to be capable of
      generating a large number of biologically active substances. The present study
      was undertaken to identify and quantify the presence of mast cells in different
      stages of human periodontal disease using histochemical (toluidine blue) and
      immunohistochemical (tryptase-positive mast cells) techniques. RESULTS: Mast cell
      densities (cells per mm(2)) were significantly increased in chronic
      periodontitis/gingivitis lesions compared with clinically healthy gingival
      tissues (Health) uniquely by immunohistochemical technique. Interestingly, mast
      cells were distributed specially in close apposition to mononuclear cells.
      CONCLUSIONS: In human periodontal disease there is an increase in the number of
      mast cells that may be participating either in the destructive events or in the
      defense mechanism of periodontal disease via secretion of cytokines, including
      perpetuation of the Th2 response, and cellular migration and healing processes.

PMID- 15984958
TI  - Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by triad
      of vascular nevi, venous varicosities and hyperplasia of soft and hard tissues in
      the affected area. This syndrome usually affects the extremities but occasionally
      can manifest in the craniofacial region, including the oral cavity. We report a
      case of KTS and discuss the oro-surgical and dental considerations regarding
      hemorrhagic tendencies caused by the known local anomalies such as vascular
      malformations associated with this syndrome as well as systemic abnormalities.

PMID- 15984959
TI  - Infliximab: lifetime use for maintenance is appropriate in Crohn's Disease. PRO:
      maintenance therapy is superior to episodic therapy.

PMID- 15984960
TI  - Infliximab: lifetime use for maintenance is appropriate in Crohn's Disease. CON:
      "lifetime use" is an awfully long time.

PMID- 15984961
TI  - Infliximab: lifetime use for maintenance is appropriate in Crohn's Disease. A
      BALANCING VIEW: lifetime channeling of infliximab for crohn's disease.

PMID- 15984962
TI  - The Health Insurance Portability and Accountability Act (HIPAA): its broad effect
      on practice.
AB  - The Health Insurance Portability and Accountability Act (HIPAA), and its final
      rule, raised fears among practitioners of new and complex regulations that might
      interfere with medical practice, lead to inadvertent liability and unwanted
      expense. It generated a dizzying set of health-care administrative activities and
      a new work for legal consultants. It has extensive scope, and includes most
      health plans and practitioners. It has regulated both privacy and security,
      including electronic, paper, and oral communications. However, after a HIPAA
      compliant office structure is established, and the privacy notice is reviewed and
      signed by the patient, disclosure of medical information for treatment, payment
      or "health-care operations" is permitted without recurrent consent forms, thus
      allowing substantially familiar patterns of doctor-to-doctor communication about
      treatment. Further, the initial approach to enforcement appears to some legal
      observers to be more likely corrective rather than punitive, although providers
      remain uneasy over the mere possibility of criminal penalties. As regards medical
      research, uncertainties about the application of HIPAA seem less resolved and
      more variably interpreted by different institutions, with ongoing fear in the
      research community that important public health and epidemiologic research
      activity may be compromised by well meaning IRBs using inconsistent, overly
      strict or erroneous interpretation of the intent of HIPAA regulations.

PMID- 15984963
TI  - Stomach (Ewald) tube.

PMID- 15984964
TI  - Decline in esophageal candidiasis and use of antimycotics in European patients
      with HIV.
AB  - BACKGROUND: Esophageal candidiasis (EC) remains one of the most common AIDS
      defining illnesses in patients with human immunodeficiency virus (HIV) in the era
      of highly active antiretroviral therapy (HAART), but little is known about
      factors associated with EC after starting HAART. OBJECTIVES: To describe changes
      in the use of antimycotic medication, the incidence of EC and factors associated
      with EC before and after starting HAART. METHODS: Patients from EuroSIDA, a pan
      European longitudinal, prospective observational study. Generalized linear models
      and poisson regression models were used to investigate the relationships.
      RESULTS: A total of 9,873 patients did not have EC at recruitment, subsequently
      537 (15.8%) developed EC. The proportion of patients taking any antimycotic
      dropped from 18% at January 1995 to 2% at January 2004 (p < 0.0001); the duration
      of treatment declined from 10 to 3 months over the same period (p < 0.0001).
      There was a 32% annual decline in the incidence of EC (95% CI 30-35%, p <
      0.0001). There was a significant annual decline in the incidence of EC pre-HAART
      in time-updated, adjusted models, (incidence rate ratio (IRR) 0.80, 95% CI 0.76
      0.85, p < 0.0001) but not post-HAART (IRR 0.97; 95% CI 0.90-1.06, p= 0.54). Older
      patients and those with low CD4 counts had the greatest incidence of EC in the
      post-HAART era. CONCLUSIONS: There has been a marked decline in the incidence of
      EC between 1994 and 2004. This was accompanied by a decline in markers associated
      with fungal disease, including use of antimycotics and a decline in duration of
      treatment.

PMID- 15984965
TI  - Declining gastrointestinal opportunistic infections in HIV-infected persons: a
      triumph of science and a challenge for our HAARTs and minds.
AB  - Gastrointestinal opportunistic infections, primarily oral and esophageal
      candidiasis, are common in persons infected with the human immunodeficiency virus
      (HIV) and contribute significantly to morbidity and mortality. Research early in
      the AIDS epidemic established a strong association between the presence of oral
      and esophageal candidiasis in patients complaining of odynophagia, demonstrated
      the diagnostic efficacy of a therapeutic trial with anti-fungal medicines, and
      defined the indications for endoscopy in HIV-infected persons with upper
      gastrointestinal complaints. Resulting diagnostic and treatment strategies with
      anti-fungal agents were very effective in preventing and treating mycotic
      infections of the gastrointestinal tract. Now, robust data from the United States
      and Europe indicate that recent advances in the development and use of highly
      active anti-retroviral therapy (HAART) are associated with a striking decline in
      the prevalence of oro-esophageal candidiasis in HIV-infected persons. In addition
      to developing more effective, safer antiviral agents, an HIV vaccine, and other
      novel approaches to combating this illness, a major challenge is to provide HAART
      to those without access to these life-saving drugs.

PMID- 15984966
TI  - Rates of endoscopy and endoscopic findings among people with frequent symptoms of
      gastroesophageal reflux in the community.
AB  - BACKGROUND: Epidemiological studies have confirmed that gastroesophageal symptoms
      are highly prevalent. However, studies linking epidemiology with clinical or
      chart data are scarce. We aimed to determine the frequency of endoscopy and
      endoscopic findings, as well as predictors of health-care utilization, among
      people with reflux symptoms in the community. METHODS: A previous survey of 2,118
      Olmsted County, MN, residents in 1993 identified 242 subjects with frequent
      reflux symptoms (at least weekly) who received care at a medical center in the
      county. Data were abstracted from Mayo Clinic records between 1988 and 1998.
      RESULTS: Overall, 130 of the 242 (54%, 95% CI 47-60%) had sought care for reflux.
      Twenty-five patients (10%) had visited a gastroenterologist; 47 (19%) had an
      upper endoscopy (EGD), 64 (26%) had an upper GI X-ray, and one had an ambulatory
      24-h esophageal pH study. Long segment Barrett's esophagus was detected in 4 (9%)
      of those having an EGD and adenocarcinoma was found in one patient with
      Barrett's. Three patients had surgery for gastroesophageal reflux disease.
      Thirteen patients (5%) died, but no deaths were due to esophageal reflux or
      adenocarcinoma. Age, higher education, frequent heartburn, and dysphagia were all
      significant, independent predictors of consulting. CONCLUSIONS: Although many
      people in the community have frequent reflux symptoms, few have investigations,
      and deaths were unrelated to reflux disease or its complications. Data from
      referral clinic or endoscopy series should not be extrapolated to the large
      numbers of people in the community with symptoms of reflux.

PMID- 15984967
TI  - Comparison of the Bravo wireless and Digitrapper catheter-based pH monitoring
      systems for measuring esophageal acid exposure.
AB  - INTRODUCTION: We compared esophageal acid exposure data obtained during
      simultaneous esophageal pH studies using the Bravo wireless and the Slimline
      catheter-Mark III Digitrapper pH systems. METHODS: Twenty-five asymptomatic
      subjects underwent endoscopy with endoclip placement at the squamocolumnar
      junction (SCJ) and manometry to localize the lower esophageal sphincter (LES). A
      Bravo capsule was placed 6 cm above the SCJ and a Slimline catheter 5 cm above
      the LES. Relative positions were checked fluoroscopically. Synchronized pH data
      were compared by manual extraction into Excel spreadsheets. An in vivo pH
      reference was established with swallows of orange juice (pH 3.88). RESULTS:
      Median acid exposure time was greater with the Slimline compared to the Bravo
      system (Slimline, 3.4%; Bravo, 1.76%, p < 0.05) but electrode positions were
      similar. The dominant source of discrepancy between systems was an offset in
      recorded pH values around pH 4 as evidenced by the recorded values of the
      swallowed orange juice. Bench-top testing suggested that this offset was mainly
      attributable to the software designed to compensate for the difference in
      electrode recording characteristics between room and body temperature. After
      adjusting the pH data sets to accurately reflect actual orange juice pH, acid
      exposure between systems was similar (Slimline, 0.90%; Bravo, 1.15%). CONCLUSION:
      The Slimline system on average over-recorded esophageal acid exposure compared to
      the Bravo system largely because of a flawed software scheme for electrode
      thermal calibration. Accuracy of pH data sets from both systems can be improved
      by scrutiny for artifacts and use of an in vivo pH reference.

PMID- 15984969
TI  - Dyspepsia and GERD: breaking the rules.
AB  - Dyspepsia is a common condition in clinical practice. Economic models have
      suggested that empirical PPI therapy may be cost-effective in uninvestigated
      dyspepsia. Empirical PPI therapy is an attractive alternative to endoscopic
      investigation in young dyspeptic patients who are not infected with Helicobacter
      pylori.

PMID- 15984968
TI  - A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in
      helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN
      Study.
AB  - BACKGROUND: The management of Helicobacter pylori negative patients with
      dyspepsia in primary care has not been studied in placebo-controlled studies.
      METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate
      severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers.
      Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine
      150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an
      additional 5 months. Treatment success was defined as no or minimal symptoms
      (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months. RESULTS:
      Five hundred and twelve patients were randomized and included in the intention-to
      treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51%
      (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22
      39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than
      all other treatments (p < 0.05). The proportion of patients who were responders
      at 4 wk and at 6 months was significantly greater for those receiving omeprazole
      31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14%
      (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053).
      The mean number of on-demand study tablets consumed and rescue antacid used was
      comparable across groups. Economic analysis showed a trade-off between superior
      efficacy and increased cost between omeprazole and ranitidine. CONCLUSION:
      Treatment with omeprazole provides superior symptom relief compared to
      ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary
      care dyspepsia patients.

PMID- 15984970
TI  - The diurnal rhythm of the cytoprotective human trefoil protein TFF2 is reduced by
      factors associated with gastric mucosal damage: ageing, Helicobacter pylori
      infection, and sleep deprivation.
AB  - OBJECTIVES: To determine if the normal TFF2 diurnal rhythm is disrupted in those
      with increased risk of gastric morbidity. Trefoil proteins protect the
      gastrointestinal mucosa from damage and aid its repair. TFF2 is considered the
      major cytoprotective gastric trefoil protein. There is a marked circadian
      variation in gastric luminal TFF2 in young healthy volunteers with peak levels
      present during the night. METHODS: Gastric juice was aspirated at two hourly
      intervals over a 24-h period via a nasogastric tube. TFF2 was measured by
      quantitative western transfer analysis. Helicobacter pylori (H. pylori) status
      was measured by C13 urea breath test and by serology. The effects of H. pylori
      infection, sleep deprivation, and ageing, which cause increased gastric
      morbidity, on the TFF2 circadian rhythm were tested. RESULTS: H. pylori infection
      attenuated the increase in TFF2 that occurs during the night. The TFF2 diurnal
      rhythm was reduced in older people and both the TFF2 level reached and the time
      at which the maximum TFF2 concentration occurs were associated inversely with age
      (p < 0.005). Sleep deprivation delayed the normal night time increase in gastric
      TFF2 and resulted in an overall reduction in TFF2 secretion. CONCLUSIONS: H.
      pylori infection, ageing, and sleep deprivation cause a reduction in the TFF2
      diurnal rhythm. The demonstration that the TFF2 rhythm is impaired in cohorts of
      individuals known to suffer gastric symptoms suggests that interventions to
      restore the normal TFF2 rhythm in those with poor mucosal protection could reduce
      morbidity.

PMID- 15984971
TI  - The utility of capsule endoscopy small bowel surveillance in patients with
      polyposis.
AB  - BACKGROUND: Small intestinal (SI) surveillance is recommended for polyposis
      patients. The utility and safety of capsule endoscopy (CE) for surveillance of SI
      neoplasia in patients with familial adenomatous polyposis (FAP) and Peutz-Jeghers
      syndrome (PJS) is unknown. METHODS: CE was offered to consecutive FAP and PJS
      patients due for routine upper endoscopic surveillance. The prevalence, location
      (jejunum, ileum), size (1-5 mm, 6-10 mm, >10 mm) and number (1-5, 6-12, >20) of
      polyps detected by CE was assessed. RESULTS: 19 subjects (15 FAP/4 PJS) with a
      mean age of 43 were included. All subjects had previous intestinal surgery. No
      complications occurred with CE. CE in FAP: 9/15 (60%) of subjects with FAP had SI
      polyps. The prevalence of SI polyps was related to the duodenal polyposis stage
      and subject age. The location, size and number of polyps progressed as duodenal
      polyposis stage advanced. CE in PJS: 3/4 (75%) of subjects with PJS had SI
      polyps. The polyps were diffuse in 2/4 and only in the ileum in one subject. CE
      findings led to laparotomy with intra-operative endoscopic polypectomy in two PJS
      patients. CONCLUSION: SI polyps are common in FAP but their importance is
      unknown. CE should be performed in FAP patients with stage III and IV duodenal
      disease. Clinically significant polyps are commonly detected by CE in PJS and
      lead to change in management in 50% of PJS subjects. CE should replace
      radiographic SI surveillance for PJS patients. CE is safe in polyposis patients
      who have undergone major intestinal surgery.

PMID- 15984972
TI  - Prospective trial of endoscopic clips versus combination therapy in upper GI
      bleeding (PROTECCT--UGI bleeding).
AB  - BACKGROUND: It is not known if combination therapy of epinephrine injection and
      multipolar electrocoagulation or hemoclips are a more efficient or effective
      treatment for patients with acute nonvariceal upper gastrointestinal (GI)
      bleeding. METHODS: Adult patients with active nonvariceal upper GI bleeding, a
      nonbleeding visible vessel, or after removal of an adherent clot findings of
      active bleeding or a visible vessel were studied. Patients were randomized to
      either therapy and the outcomes were assessed at 30 days. RESULTS: Forty-seven
      patients were studied: 26 patients randomized to hemoclips and 21 to combination
      therapy. There were 22 patients with active bleeding, 13 with a nonbleeding
      visible vessel, and 12 with an adherent clot. The median duration of endoscopic
      therapy was 17 min in the hemoclip group versus 20 min for the combination
      therapy, p= 0.29. Primary hemostasis with successful initial control of bleeding
      occurred in 26 (100%) of 26 hemoclip patients and 20 (95.2%) of 21 combination
      therapy patients, p= 0.45. The rebleeding rates were: 4 (15.4%) of 26 hemoclip
      patients versus 5 (23.8%) of 21 combination therapy patients, p= 0.49. Overall,
      the length of hospital stay, units of blood transfused, surgery rates, and
      mortality were not different. CONCLUSIONS: In this prospective, randomized
      controlled trial of endoscopic hemoclips versus combination therapy in the
      nonvariceal upper GI bleeding, the efficiency, efficacy, and complications of the
      two treatment modalities were not significantly different.

PMID- 15984973
TI  - Insulin resistance plays a significant role in liver fibrosis in chronic
      hepatitis C and in the response to antiviral therapy.
AB  - OBJECTIVES: To assess whether insulin resistance is associated with liver
      fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection
      and whether there were any differences in insulin resistance between Asians and
      the indigenous Caucasian population. Secondly, to assess whether insulin
      resistance is associated with sustained virological response to antiviral
      therapy. METHODS: We determined insulin resistance in 59 (30 Caucasians; 29
      Asians) consecutive patients with HCV prior to starting antiviral therapy.
      Insulin resistance was measured using the homeostasis model assessment of insulin
      resistance (HOMA-IR). The relationship between insulin resistance and
      biochemical, virological, and histological data together with response to
      antiviral therapy was assessed. RESULTS: In multivariable analyses, insulin
      resistance as measured using the HOMA-IR model correlated positively with the
      stage of fibrosis, with higher degrees of insulin resistance in those with
      greater degrees of fibrosis (p < 0.001). This significant relationship remained
      even after excluding cirrhotic patients, or after adjusting for other factors
      associated with fibrosis in univariable analyses. Insulin resistance was
      significantly higher in Asians than Caucasians (p= 0.004). Around half (55.6%) of
      patients completing a course of antiviral treatment had a sustained virological
      response. Multivariable logistic regression identified HCV genotype 3, lower
      fasting glucose levels, and lower aspartate transaminase (AST) levels as being
      associated with a higher odds of a sustained virological response. After
      adjusting for these variables, Asian ethnicity, higher fasting insulin levels,
      and higher HOMA-IR levels were all associated with a poorer virological response
      to therapy. CONCLUSIONS: Insulin resistance contributes to liver fibrosis in
      chronic HCV infection; this relationship is not genotypic specific. Asian
      patients had higher insulin resistance than Caucasians. Insulin resistance is
      also an important predictor of sustained response to antiviral therapy.

PMID- 15984974
TI  - Clinical course and outcome of autoimmune hepatitis/primary sclerosing
      cholangitis overlap syndrome.
AB  - Autoimmune hepatitis/primary sclerosing cholangitis (AIH/PSC) overlap syndrome is
      a relatively uncommon variant of PSC. AIM: To evaluate the natural history of
      AIH/PSC overlap syndrome compared to a group of "classical" PSC. METHODS: Forty
      one consecutive PSC patients, with a regular follow-up of at least 2 years, were
      prospectively included in the study. Among these, 7 fulfilled the criteria for
      AIH/PSC overlap syndrome. RESULTS: The AIH/PSC overlap group significantly
      differed from the "classical" PSC group in the following parameters: mean age at
      presentation (21.4 +/- 5.0 vs 32.3 +/- 10 years, p < 0.01), AST 191.0 +/- 14.8 vs
      48.9 +/- 34.5 U/L, p < 0.005), ALT (357.0 +/- 26.5 vs 83.7 +/- 60.7 U/L, p <
      0.005) and serum IgG (25.6 +/- 4.7 vs 12.9 +/- 6.0 mg/dl, p < 0.0001). The mean
      follow-up was similar in the 2 groups (93.3 +/- 65.9 vs 98.1 +/- 65.9 months
      respectively). Treatment included immunosuppression + ursodeoxycholic acid (UDCA)
      in the AIH/PSC overlap patients, and UDCA in the "classical" PSC group. Deaths
      were recorded only in the classical PSC group. The median survival in the latter
      group was 207 months (95% C.I. 87.6-326.4). The major events during the follow-up
      included: OLTx (1/7 vs 6/34), and neoplasms (only in the group of "classical"
      PSC). The new Mayo score prognostic index only increased significantly during
      follow-up in the "classical" PSC group (r2 0.8117, p < 0.01) CONCLUSION: Patients
      with AIH/PSC overlap syndrome seem to benefit from immunosuppression + UDCA
      therapy, survival is apparently better than in "classical" PSC condition.

PMID- 15984975
TI  - Outcome of small (10-20 mm) arterial phase-enhancing nodules seen on triphasic
      liver CT in patients with cirrhosis or chronic liver disease.
AB  - OBJECTIVE: To determine the outcome of small arterial phase-enhancing nodules, 10
      20 mm, seen on serial triphasic liver CT scans in a hepatocellular cancer
      screening population. METHODS: Of 58 patients referred for triphasic liver CT, 20
      (18 men, 2 women) with 32 nodules formed the study group. Each patient in the
      study group had at least two CT scans, a minimum of 3 months follow-up, at least
      one nodule measuring 10-20 mm, no prior diagnosis of hepatocellular carcinoma,
      and no nodule greater than 20 mm typical of hepatocellular carcinoma at the time
      of the first CT. Serial CT scans were reviewed by an abdominal imaging
      radiologist who classified the nodules as stable, decreasing, or increasing in
      size. RESULTS: A mean of six CT studies (range 2-10) were performed for each
      patient with a mean follow-up of 25 months (range 4-47 months). Of 32 nodules, 14
      (44%) were stable, 9 (28%) decreased, and 9 (28%) increased in size. Nodules that
      increased in size were treated as hepatocellular carcinoma: six were
      hepatocellular carcinoma, two were biopsy negative but showed recurrent tumor
      after radiofrequency ablation, and one was a high-grade dysplastic nodule. Mean
      doubling time for these nine nodules was 5.7 months (range 2.3-10.8 months).
      CONCLUSIONS: Most small (10-20 mm) arterial phase-enhancing nodules seen on
      triphasic liver CT are not hepatocellular carcinoma. Serial CT is useful to guide
      management in these patients. Growth of small arterial phase-enhancing nodules
      can be used as an indicator that the nodule should be treated as hepatocellular
      carcinoma.

PMID- 15984976
TI  - Detection and Isolation of Mycobacterium avium subspecies paratuberculosis from
      intestinal mucosal biopsies of patients with and without Crohn's disease in
      Sardinia.
AB  - OBJECTIVES: Sardinia is an island community of 1.6 million people. There are also
      about 3.5 million sheep and one hundred thousand cattle in which Johne's disease
      and Mycobacterium avium subspecies paratuberculosis infection are endemic. The
      present study was designed to determine what proportion of people in Sardinia
      attending for ileocolonoscopy with or without Crohn's disease were infected with
      this pathogen. METHODS: Mycobacterium avium subspecies paratuberculosis was
      detected by IS900 PCR on DNA extracts of fresh intestinal mucosal biopsies as
      well as by isolation in culture using supplemented MGIT media followed by PCR
      with amplicon sequencing. RESULTS: Twenty five patients (83.3%) with Crohn's
      disease and 3 control patients (10.3%) were IS900 PCR positive (p = 0.000001;
      Odds ratio 43.3). Mycobacterium avium subspecies paratuberculosis grew in
      cultures from 19 Crohn's patients (63.3%) and from 3 control patients (10.3%) (p
      = 0.00001; Odds ratio 14.9). All patients positive by culture had previously been
      positive by PCR. Mycobacterium avium subspecies paratuberculosis first appeared
      in the liquid cultures in a Ziehl Neelsen (ZN) staining negative form and
      partially reverted through a rhodamine-auramine positive staining form to the
      classical ZN positive form. This resulted in a stable mixed culture of all 3
      forms illustrating the phenotypic versatility of these complex chronic enteric
      pathogens. CONCLUSIONS: Mycobacterium avium subspecies paratuberculosis was
      detected in the majority of Sardinian Crohn's disease patients. The finding of
      the organism colonizing a proportion of people without Crohn's disease is
      consistent with what occurs in other conditions caused by a primary bacterial
      pathogen in susceptible hosts.

PMID- 15984977
TI  - The mycobacteria story in Crohn's disease.
AB  - The heterogeneity of Crohn's disease suggests that it would be unwise to dismiss
      an infectious contribution to the pathogenesis in a subset of patients. The most
      enduring infectious candidate has been Mycobacterium paratuberculosis, which
      appears to be widespread in nature and appears to have the potential to infect
      humans. However, there are many counterarguments to the notion that MAP causes
      Crohn's disease, and numerous observations are seemingly at variance with this
      concept.

PMID- 15984978
TI  - VSL#3 probiotic-mixture induces remission in patients with active ulcerative
      colitis.
AB  - BACKGROUND AND AIMS: Intestinal bacteria have been implicated in the initiation
      and perpetuation of IBD; in contrast, "probiotic bacteria" have properties
      possibly effective in treating and preventing relapse of IBD. We evaluated the
      safety and efficacy of VSL#3 and the components, and the composition of the
      biopsy-associated microbiota in patients with active mild to moderate ulcerative
      colitis (UC). METHODS: Thirty-four ambulatory patients with active UC received
      open label VSL#3, 3,600 billion bacteria daily in two divided doses for 6 wk. The
      presence of biopsy-associated bacteria was detected using a nucleic acid-based
      method and the presence of VSL#3 species confirmed by DNA sequencing of 16S rRNA.
      RESULTS: Thirty-two patients completed 6 wk of VSL#3 treatment and 2 patients did
      not have the final endoscopic assessment. Intent to treat analysis demonstrated
      remission (UCDAI < or = 2) in 53% (n = 18); response (decrease in UCDAI > or = 3,
      but final score > or =3) in 24% (n = 8); no response in 9% (n = 3); worsening in
      9% (n = 3); and failure to complete the final sigmoidoscopy assessment in 5% (n =
      2). There were no biochemical or clinical adverse events related to VSL#3. Two of
      the components of VSL#3 were detected by PCR/DGGE in biopsies collected from 3
      patients in remission. CONCLUSION: Treatment of patients with mild to moderate
      UC, not responding to conventional therapy, with VSL#3 resulted in a combined
      induction of remission/response rate of 77% with no adverse events. At least some
      of the bacterial species incorporated in the probiotic product reached the target
      site in amounts that could be detected.

PMID- 15984979
TI  - Is perianal Crohn's disease associated with intestinal fistulization?
AB  - BACKGROUND: When cases of Crohn's disease (CD) are described as "fistulizing,"
      distinctions are often not drawn between perianal and intestinal fistulization.
      The question, therefore, remains open as to whether or not there is truly an
      association between perianal fistulization and intraabdominal intestinal
      fistulization in CD. AIMS: We have sought to determine the association between
      perianal and intestinal fistulization by analyzing the cases of CD recorded in
      databases from six international centers. PATIENTS: Six databases provided
      information on 5491 cases of CD in the United States, France, Italy, and The
      Netherlands. Of these cases, 1686 had isolated ileal disease and 1655 had Crohn's
      colitis. METHODS: An association between perianal disease and internal fistulae
      was sought by calculating relative risks for the chance of internal fistulae
      among patients with perianal fistulae relative to those without. Statistical
      significance was calculated by the Mantel-Haenszel procedure, stratifying on the
      separate centers. All statistical tests and estimates were implemented using SAS
      for the PC. RESULTS: Among the 1686 cases with isolated ileal disease, the
      evidence of an association between perianal disease and internal fistulization
      was not consistent across centers, with relative risks ranging from 0.8 to 2.2.
      For patients with Crohn's colitis (n = 1655), the association was much stronger
      and more consistent, with an estimated common relative risk of 3.4, 95%
      confidence interval (2.6-4.6, p < 0.0001). CONCLUSIONS: We have found a
      statistically significant association between perianal CD and intestinal
      fistulization, much stronger and more consistent in cases of Crohn's colitis than
      in cases limited to the small bowel.

PMID- 15984980
TI  - Food-specific serum IgG4 and IgE titers to common food antigens in irritable
      bowel syndrome.
AB  - INTRODUCTION: Food hypersensitivity is a common perception among irritable bowel
      syndrome (IBS) patients. Data from dietary elimination and food challenge studies
      support an etiopathological role of diet in IBS, but there are no well
      established tests to identify food hypersensitivity. AIM: To compare IgG4 and IgE
      titers to common food antigens in IBS and controls. METHOD: One hundred and eight
      IBS [52 diarrhea-predominant (D-IBS); 32 constipation-predominant (C-IBS); 24
      alternating (Alt-IBS)], and 43 controls were included in the study. IgG4 and IgE
      titers and skin prick testing (SPT) to 16 common foods including milk, eggs,
      cheese, wheat, rice, potatoes, chicken, beef, pork, lamb, fish, shrimps, soya
      bean, yeast, tomatoes, and peanuts were measured. RESULTS: IBS had significantly
      higher IgG4 titers (mug/L) to wheat (395 IQR +/- 1,011 vs 0 IQR +/- 285, p <
      0.001), beef (1,079 IQR +/- 930 vs 617 IQR +/- 435, p < 0.001), pork (481 IQR +/-
      379 vs 258 IQR +/- 496, p < 0.001), and lamb (241 IQR +/- 460 vs 167 IQR +/- 232,
      p= 0.009) compared to controls. These differences were maintained across all
      three subgroups. The antibody titers to potatoes, rice, fish, chicken, yeast,
      tomato, and shrimps were not significantly different. No significant difference
      in IgE titers was observed between IBS and controls. SPT was positive for only a
      single antigen in 5 of 56 patients tested with the same panel of foods. No
      correlation was seen between the pattern of elevated IgG4 antibody titers and
      patients' symptoms. CONCLUSION: Serum IgG4 antibodies to common foods like wheat,
      beef, pork, and lamb are elevated in IBS patients. In keeping with the
      observation in other atopic conditions, this finding suggests the possibility of
      a similar pathophysiological role for IgG4 antibodies in IBS.

PMID- 15984981
TI  - IgG-mediated food intolerance in irritable bowel syndrome: a real phenomenon or
      an epiphenomenom?
AB  - Abnormal reactions to food probably contribute to the complex pathophysiology of
      irritable bowel syndrome, but the mechanisms involved remain unclear. Following
      the recent identification of subtle mucosal inflammation in at least some
      patients with the disorder, perhaps now is the time to revisit some of the
      immunological reactions to dietary antigens that, in the past, have been
      dismissed as irrelevant.

PMID- 15984982
TI  - Infusion of neostigmine-glycopyrrolate for bowel evacuation in persons with
      spinal cord injury.
AB  - Defecatory complications are common after spinal cord injury (SCI) and have been
      attributed, in part, to an imbalance of the autonomic nervous system between
      parasympathetic and sympathetic effects on the colon. Because parasympathetic
      (i.e., cholinergic) input to the bowel may be downregulated after SCI, it was
      hypothesized that neostigmine, a medication that increases cholinergic tone by
      blocking the metabolism of acetylcholine, might promote bowel evacuation in these
      persons. Since neostigmine is known to cause bradycardia and bronchoconstriction,
      we also assessed whether these side-effects could be prevented by
      coadministration of neostigmine with glycopyrrolate, an anticholinergic agent
      that has limited activity on the muscarinic receptors of the colon. The
      hypothesis was tested in 13 persons with SCI in whom videofluoroscopy was carried
      out after instillation of a barium oatmeal paste into the rectum and descending
      colon. On separate days, subjects received, in a randomized, blinded design, one
      of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg
      neostigmine + 0.4 mg glycopyrrolate). The effect of these infusates on bowel
      evacuation of the barium paste, heart rate, and airway resistance was determined.
      Both neostigmine and neostigmine + glycopyrrolate resulted in prompt bowel
      evacuation. The nadir heart rate was lower after neostigmine alone than with the
      combination. Neostigmine administration increased both total and central airway
      resistance, an effect that was not observed with the coadministration of
      glycopyrrolate. Other side-effects of neostigmine and the combination of drugs
      included muscle fasciculations and dry mouth, both of which were mild and short
      lived. Abdominal cramping was noted in subjects with spinal cord lesions below
      thoracic level 10. These results indicated that neostigmine/glycopyrrolate
      administration is safe and well tolerated in persons with chronic SCI.

PMID- 15984983
TI  - Detection of bacterial overgrowth in IBS using the lactulose H2 breath test:
      comparison with 14C-D-xylose and healthy controls.
AB  - OBJECTIVES Recent reports suggest bacterial overgrowth is commonly associated
      with irritable bowel syndrome (IBS) when diagnosed using the lactulose hydrogen
      breath test (LHBT). We employed this test to examine whether similar findings
      exist in a geographically distinct population of Rome II positive IBS patients
      and compared it to the 14C-D-xylose breath test, a test with acknowledged greater
      specificity for bacterial overgrowth. METHODS: In the first series, Rome II IBS
      patients underwent a 10 g lactulose breath test and a standardized 1 g 14C-D
      xylose breath test and answered IBS symptom questionnaires. A positive test
      required an elevated breath hydrogen concentration within 90 min, two distinct
      peaks, and an increase >20 ppm. In a second series, control patients lacking
      gastrointestinal symptoms underwent a lactulose breath test. A positive test
      required an elevation of breath hydrogen >20 ppm within 90 or 180 min. These
      criteria were also applied to lactulose breath tests from IBS cases in series
      one. RESULTS: The IBS patients were predominantly female (64%) and most reported
      severe symptoms (80%). The majority had diarrhea predominant symptoms (63%) and
      only 3% were constipation predominant. In the first series, only 10% of patients
      had a positive lactulose breath test and 13% had a positive 14C-D-xylose test. In
      the second series, the number of abnormal LHBTs was much higher but no
      differences were found between IBS patients and controls. CONCLUSION: The
      lactulose breath test did not reliably detect a common association between
      bacterial overgrowth and IBS in our patient population.

PMID- 15984984
TI  - A prospective study of gastric emptying and its relationship to the development
      of nausea, vomiting, and anorexia after autologous stem cell transplantation.
AB  - BACKGROUND AND AIMS: Gastric motor dysfunction may be responsible, in some
      patients, for the nausea and emesis that occur following high-dose chemotherapy
      (HDT) and autologous stem cell transplantation (SCT). We sought to define the
      prevalence of gastric emptying abnormalities and their relationship to the
      development of nausea, vomiting, and anorexia in patients undergoing HDT and
      autologous SCT. METHODS: We prospectively studied patients with a variety of
      malignancies who received standard transplantation doses of chemotherapeutic
      agents and antiemetics. Gastric emptying was assessed prior to HDT and on Days 0
      (day of stem cell infusion), +7, and +14 from SCT. Symptom assessment was
      obtained daily from initiation of HDT to 28 days after SCT. RESULTS: Twenty-four
      patients were studied. Prior to HDT, gastric emptying was rapid in two patients.
      Nausea, emesis, and anorexia occurred in all patients, peaked in severity at Day
      +7 after SCT and, with the exception of anorexia, had returned toward baseline
      levels by Day +28. As a group, gastric emptying was significantly slower on Days
      0 and +7 and returned to baseline level by Day +14. Twenty-six percent and 44% of
      patients demonstrated delayed gastric emptying (T(1/2) >90 min) on Days 0 and +7,
      respectively, while 13% and 31% of patients had rapid gastric emptying (T(1/2)
      <30 min) on Days 0 and +7, respectively. Thirty-nine percent and 75% of patients
      had either rapid or delayed gastric emptying on Days 0 and +7, respectively.
      There was an association between delayed gastric emptying and moderate-severe
      anorexia on Day +7 and between delayed gastric emptying and at least mild
      vomiting on Day 0. Additionally, there was an association between rapid gastric
      emptying and at least mild vomiting on Day +7. Finally, an association was found
      between either rapid or delayed gastric emptying and at least mild nausea on Day
      +7. CONCLUSION: Both delayed and rapid gastric emptying occur commonly during the
      2-wk period following HDT and autologous SCT and may be responsible, at least in
      part, for upper gastrointestinal symptoms that occur in these patients.

PMID- 15984985
TI  - Rectal intussusception: a study of rectal biomechanics and visceroperception.
AB  - OBJECTIVES: Rectal intussusception (RI) is a significant cause of morbidity
      amongst those with a rectal evacuatory disorder. The pathophysiology is unknown,
      but may involve abnormal biomechanics of the rectal wall similar to that
      previously demonstrated in patients with overt rectal prolapse (RP). Using an
      electromechanical barostat, this study aimed to investigate the biomechanics and
      visceroperception of the rectal wall in patients with RI. METHODS: Twenty
      consecutive patients (12 females, median age 46 yr (range 24-66)) with
      symptomatic, full-thickness RI were studied. Patients underwent assessment of
      rectal compliance, visceroperception, adaptive response to isobaric distension at
      urge threshold, and assessment of the postprandial response. Results were
      compared with those obtained in 28 asymptomatic volunteers, 10 with RI (6
      females, median age 29 yr (range 21-36)) and 18 (9 females, median age 33 yr
      (range 21-62)) without. RESULTS: In the absence of the clinical finding of
      solitary rectal ulcer syndrome (SRUS), patients with symptomatic RI have normal
      rectal wall biomechanics, as do asymptomatic volunteers with RI (p < 0.05).
      Patients with the clinical finding of SRUS had reduced compliance and adaptation.
      In all three groups, there was a linear relationship between rectal pressure and
      visceroperception. The postprandial contractile response was similar between
      groups. CONCLUSIONS: Patients with RI have normal rectal wall biomechanics. This
      is in contrast to patients with RP, and suggests that while they may represent
      different stages of the same disease process, they are physiologically distinct.
      In patients with RI and SRUS, rectal wall inflammation and fibrosis, perhaps
      arising secondary to the intussusception, may explain the physiological changes
      observed.

PMID- 15984986
TI  - Positive predictive value of fecal occult blood testing in persons taking
      warfarin.
AB  - BACKGROUND: In clinical practice, some physicians discontinue warfarin prior to
      fecal occult blood testing (FOBT). Although anticoagulant use is associated with
      an increased risk of overt gastrointestinal bleeding, the impact of warfarin on
      the positive predictive value of FOBT is unknown. METHODS: During a 5-yr period,
      we prospectively studied all patients taking warfarin who were referred for the
      evaluation of a positive FOBT. For each patient taking warfarin, we enrolled one
      age- and gender-matched control subject with a positive FOBT who was not taking
      anticoagulants. A detailed clinical history was obtained, and all subjects
      underwent colonoscopy and esophagogastroduodenoscopy. RESULTS: Lesions consistent
      with occult bleeding were identified in 59.0% of the 210 patients in the warfarin
      group and 53.8% of the 210 control subjects (p= 0.27). Although more lesions were
      identified by colonoscopy in the warfarin group than in control subjects (36.2%vs
      25.7%, p= 0.02), there was no difference in the frequency of lesions identified
      by esophagogastroduodenoscopy (35.2%vs 39.5%, p= 0.43). Overall, adenomas > or =1
      cm in diameter (16.2%) and colorectal carcinoma (9.5%) were the most common
      lesions identified by colonoscopy, while erosive gastritis (15.5%) and erosive
      duodenitis (11.0%) were the most frequent lesions found by
      esophagogastroduodenoscopy. Among individuals with colorectal cancer, 83.3% of
      patients in the warfarin group had early cancers (Dukes' stage A or B) compared
      with 50.0% of control subjects (p= 0.046). CONCLUSIONS: Warfarin use did not
      decrease the positive predictive value of FOBT. These findings suggest that
      warfarin should not be discontinued prior to FOBT.

PMID- 15984987
TI  - The clinical value of procalcitonin in early assessment of acute pancreatitis.
AB  - OBJECTIVES: Early assessment of the severity and the etiology is crucial in the
      management of acute pancreatitis. To determine the value of procalcitonin (PCT)
      as a prognostic marker and as an indicator of biliary etiology in the early phase
      of acute pancreatitis. METHODS: In a prospective study, 75 consecutive patients
      were included (severe pancreatitis in 12 patients, biliary etiology in 42 cases).
      The value of PCT as a prognostic marker was compared to C-reactive protein (CRP),
      hematocrit (HCT), acute physiology and chronic health evaluation (APACHE) II
      score, and Ranson score. The value of PCT as an indicator of biliary etiology was
      compared to alanine aminotransferase (ALT) and alkaline phosphatase (AP). The
      area under the receiver operating characteristic curve (AUC) was applied as a
      measure of the overall accuracy of the single markers and multiple scoring
      systems. RESULTS: The most accurate prediction of severe disease was provided by
      the APACHE II score on the day of admission (AUC: APACHE II, 0.78; CRP, 0.73;
      HCT, 0.73; and PCT, 0.61), and by CRP after 48 h (AUC: CRP, 0.94; Ranson score,
      0.81; PCT, 0.71; APACHE II score, 0.69; and HCT, 0.46). ALT was the most accurate
      indicator of biliary pancreatitis (AUC: ALT, 0.83; AP, 0.81; and PCT, 0.68).
      CONCLUSIONS: PCT is of limited additional value for early assessment of severity
      and etiology in acute pancreatitis. CRP is found to be a reliable prognostic
      marker with a delay of 48 h, while ALT is validated as the best indicator of
      biliary etiology.

PMID- 15984988
TI  - TNF promoter polymorphisms and modulation of growth retardation and disease
      severity in pediatric Crohn's disease.
AB  - OBJECTIVES: Delayed growth is common in pediatric Crohn's disease (CD). Multiple
      factors have been shown to affect growth in this situation, the most prominent
      being the presence and severity of inflammation and inadequate nutritional
      intake. Inflammation, anorexia, and weight loss are all manifestations of
      circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha
      may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study
      was to determine whether growth retardation and disease severity in pediatric
      onset CD are affected by TNF promoter genotype. METHODS: Genotyping for TNF-alpha
      and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with
      detailed growth records. Parameters including disease location and disease
      severity were recorded, and the effect of these polymorphisms on Z-scores for
      height and weight at disease onset and during follow-up were analyzed. RESULTS:
      Lower age of onset was linked to more height retardation, while the presence of
      colonic disease and the absence of ileal disease were more likely to predict the
      absence of growth retardation. The presence of two polymorphisms thought to
      decrease circulating TNF-alpha was associated with higher mean Z-scores for
      height and a trend toward less growth retardation. Two other polymorphisms were
      modestly associated with disease severity. CONCLUSION: Polymorphisms in the TNF
      alpha promoter may independently modulate growth and disease severity in
      pediatric onset CD. The effect of these polymorphisms does not appear to be
      mediated via weight loss, and is relatively modest.

PMID- 15984989
TI  - Clinical utility of diagnostic tests for constipation in adults: a systematic
      review.
AB  - BACKGROUND AND AIMS: Because symptoms alone do not identify pathophysiology or
      differentiate subgroups of constipation, diagnostic tests are generally
      recommended. However, their utility is not known. We performed a systematic
      review of diagnostic tests commonly used in constipation. METHODS: We searched
      the English literature using MEDLINE and PUBMED databases from 1966 to 2004 for
      studies in adults published as full manuscripts whose methodological quality was
      above a minimum score. RESULTS: No studies assessed the routine use of blood
      tests or abdominal x-ray. One retrospective endoscopic study showed that cancer
      and polyp detection rate was comparable to historical controls. Two studies of
      barium enema were unhelpful in diagnosis of constipation. Physiological studies
      showed differences in study population, methodology, and interpretation, and
      there was no gold standard. Ten colonic transit studies showed prevalence of 38
      80% in support of slow transit constipation. Nine anorectal manometry studies
      showed prevalence of 20-75% for detecting dyssynergia. Nine studies of balloon
      expulsion showed impaired expulsion of 23-67%. Among 10 defecography studies,
      abnormalities were reported in 25-90% and dyssynergia in 13-37%. CONCLUSIONS:
      Evidence to support the use of blood tests, radiography, or endoscopy in the
      routine work up of patients with constipation without alarm features is lacking.
      Colonic transit, anorectal manometry, and balloon expulsion tests reveal
      physiologic abnormalities in many selected patients with constipation, but no
      single test adequately defines pathophysiology. Large, well-designed, prospective
      studies are required to examine the utility of these tests.

PMID- 15984990
TI  - Focal nodular hyperplasia in identical twins.
AB  - A unique case of a focal nodular hyperplasia (FNH) in identical twins is
      presented. The computed tomography (CT) and magnetic resonance imaging (MRI) of
      the abdomen demonstrated in both twins a mass of identical size in the same
      segment of their liver. Histopathologic examination of both masses confirmed the
      diagnosis of focal nodular hyperplasia. This case report strongly supports the
      theory of a congenital vascular anomaly playing a major role in the etiology of
      focal nodular hyperplasia.

PMID- 15984991
TI  - Helicobacter pylori and GERD.

PMID- 15984992
TI  - Acute pancreatitis after kidney transplantation.

PMID- 15984993
TI  - The role of proximal pH monitoring.

PMID- 15984995
TI  - Dual pH monitoring to detect food and beverage artifacts.

PMID- 15984996
TI  - Value of AST/ALT ratio as fibrotic predictor in chronic hepatitis C.

PMID- 15984997
TI  - Tuberculous peritonitis.

PMID- 15984999
TI  - Interstitial pneumonia recurrence during chronic hepatitis C treatment.

PMID- 15985000
TI  - Successful treatment of chronic hepatitis D with a short course of peginterferon
      alfa-2a.

PMID- 15985001
TI  - Direct percutaneous endoscopic jejunal feeding tube placement.

PMID- 15985003
TI  - Treatment of chronic hepatitis B.
AB  - In the last years, marked progress has been made in the treatment of chronic
      hepatitis B. The efficacy of lamivudine, the first nucleoside analogue available,
      is limited by the high incidence of resistance. Adefovir, which was recently
      approved has a comparable efficacy with a very low frequency of resistance.
      However, adefovir needs to be indefinitely administered as withdrawal of therapy
      is generally associated with reactivation and sustained response is uncommon.
      Recent large randomized controlled trials showed that PEG IFNs induce relatively
      high sustained response rates both in HBeAg positive and HBeAg negative chronic
      hepatitis B. So far, the combination of PEG IFN with lamivudine, used
      simultaneously, is disappointing in terms of short-term efficacy. However, long
      term efficacy needs to be assessed and different schedules of combination (for
      example sequential) need to be evaluated. A number of nucleoside analogues, with
      favourable toxicity profiles and a promise of increased effectiveness against
      HBV, are at various stages of clinical development. Results of phase III trials
      of entecavir and emtricitabine confirmed their efficacy. However, while entecavir
      is associated with a low incidences of resistance, emtricitabine is associated
      with a relatively high incidence of resistance which limits its use as a
      monotherapy. The efficacy and safety of new and more potent drugs like
      telbivudine and clevudine need to be confirmed. The future of chronic hepatitis B
      therapy seems to be in the combination of different drugs. Ideally, the optimal
      drugs to combine would meet the following criteria: they should have different
      sites of action on HBV DNA replication, a potent antiviral effect, an excellent
      safety profile and they should induce a sustained response with a limited
      duration of therapy. Indeed, the concept of combination therapy has been recently
      developed in order to increase efficacy and to decrease the occurrence of viral
      resistance. However, so far few combinations have been evaluated. No combination
      therapy demonstrated a benefit as compared with monotherapy. More potent drugs
      and new combinations together with the understanding of the mechanisms of
      resistance to therapy are important challenges to improve the efficacy of
      treatment and decrease in the future the global burden related to chronic
      hepatitis B.

PMID- 15985004
TI  - Inhibition of hepatitis B virus by lentiviral vector delivered antisense RNA and
      hammerhead ribozymes.
AB  - Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and
      hepatocellular carcinoma. Current treatments are limited and may be ineffective.
      Nucleic acid-mediated targeting of viral mRNA is an attractive and specific
      approach for viral infection and lentiviral vectors provide a means to express
      antisense sequences or ribozymes stably in target cells permitting continuous
      production within that cell and its progeny. To demonstrate long-term gene
      expression by lentiviral vectors in hepatocytes and to introduce lentiviral
      vectors expressing anti-HBV genes to assess their effect against HBV, lentiviral
      vectors expressing a reporter gene were assessed for longevity of gene expression
      in hepatocytes in vitro. Hammerhead ribozymes and antisense sequences targeting
      the HBV encapsidation signal (epsilon), X or surface antigen on mRNAs were cloned
      into lentiviral vectors and used to transduce HBV expressing hepatocytes where
      the effect on HBV mRNA level was assessed using ribonuclease protection. Gene
      expression in hepatocytes from integrated vectors continued for over 4 months
      without selection. Antisense RNA targeting HBs mRNA reduced this transcript,
      whilst antisense RNA to HBX mRNA was ineffective. Sense RNAs corresponding to
      epsilon and HBX mRNA also reduced HBV mRNA levels. Ribozymes targeting HBs and
      HBX mRNA effectively reduced HBV mRNA levels compared with inactive constructs
      indicating their effect to be enzymatic rather than antisense. Lentiviral vectors
      can produce long-term gene expression in hepatocytes and thus permit prolonged
      expression of antiviral genes targeting the HBV encapsidation signal, surface and
      X mRNAs as treatments for chronic HBV infection.

PMID- 15985005
TI  - Differentially expressed cellular genes following HBV: potential targets of anti
      HBV drugs?
AB  - The aim of the study was to screen for cellular genes that are differentially
      expressed following hepatitis B virus (HBV) infection, in an attempt to identify
      potential targets of anti-HBV drugs. An oligonucleotide microarray containing 231
      virus-infection-associated genes was prepared. Differential gene expression in
      HepG2.2.15 cells compared to control with HepG2 cells was analysed by this in
      house microarray. The change in gene expression in HepG2.2.15 cells treated by
      lamivudine on days 4 and 8 after exposure was also studied. Semi-quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) was used to comfirm the
      differentially expressed genes induced by HBV and lamivudine. There were 31
      upregulated and four downregulated genes in HepG2.2.15 cells compared with the
      HepG2 control cells. Eleven genes were consistently altered by lamivudine at both
      time points. Of the 31 genes that were upregulated in HepG2.2.15 cells, there
      were seven genes which were downregulated by lamivudine. Of the four
      downregulated genes, there was one gene which was upregulated by lamivudine. Of
      the differentially expressed genes induced by HBV and lamivudine, the expression
      of five genes was confirmed by semi-quantitative RT-PCR. These results shed new
      light on the effects of HBV and lamivudine on cellular gene expression.
      Differentially expressed genes induced by HBV and lamivudine could potentially
      become new anti-HBV drug targets in novel therapies.

PMID- 15985006
TI  - Viral dynamics during tenofovir therapy in patients infected with lamivudine
      resistant hepatitis B virus mutants.
AB  - Tenofovir, an antihuman immunodeficiency virus (HIV) drug, has activity against
      lamivudine-resistant hepatitis B virus (HBV) mutants. To describe the efficacy of
      tenofovir in patients with lamivudine-resistant hepatitis B we applied two
      investigative approaches based on mathematical models of viral dynamics: the
      individual nonlinear fitting and the mixed-effect group fitting approaches.
      Eleven chronic HBV patients on lamivudine for a median of 176 weeks (range: 72
      382) with YMDD mutation-related HBV-DNA breakthrough received 'add-on' tenofovir
      300 mg once-daily, while maintaining their existing therapy. Sequential sera were
      taken at day 1 (t = 0 and t = 8 h), days 2, 4, 7, 10, 14, 21, 28 and every 4
      weeks thereafter, and HBV-DNA levels were assessed using a validated quantitative
      polymerase chain reaction (PCR) assay. Median baseline log HBV-DNA was 8.62
      (range: 6.48-9.76 log HBV-DNA). Tenofovir treatment resulted in a mean (+/-SD)
      log HBV-DNA decline of 1.37 +/- 0.51 in the first phase, 2.54 +/- 0.91 after 4
      weeks, and 4.95 +/- 0.90 log HBV-DNA after 24 weeks. The median effectiveness of
      blocking viral replication in the individual fit model was 93% (range: 73-99) for
      eta = 0 and 93% (range: 59-99) for eta = 1. There was only a small difference
      between the efficacy parameter 'epsilon' of the individual nonlinear fitting and
      mixed-effect group fitting on the biphasic exponential model. These data show
      that tenofovir has good efficacy in blocking viral replication in HBV patients
      with lamivudine-induced drug-resistant HBV mutants, but effectiveness varies
      greatly among individuals. Both models can be used to describe viral decay during
      tenofovir therapy.

PMID- 15985007
TI  - The relationship between HBV-DNA levels and cirrhosis-related complications in
      Chinese with chronic hepatitis B.
AB  - We studied the hepatitis B virus (HBV)-DNA levels below which the development of
      cirrhosis-related complications became unlikely in chronic hepatitis B (CHB).
      Seventy-nine Chinese CHB patients with cirrhosis-related complications and 158
      age-, sex- and HBeAg status-matched patients without complications were enrolled.
      The precore and core promoter mutations were detected by the Line Probe assay
      (LiPA). HBVDNA levels were determined by Digene assay and Cobas Amplicor Monitor
      test. Patients with complications had higher HBVDNA levels than those without
      complications (P = 0.02). HBeAg-positive patients with complications had similar
      alanine transferase (ALT) and HBVDNA levels and frequency of precore mutations,
      but higher frequency of core promoter mutations (P = 0.003), compared with those
      without complications. Anti-HBe-positive patients with complications had higher
      ALT and HBVDNA levels (P < 0.01) but similar frequency of precore and core
      promoter mutations, compared with those without complications. Anti-HBe patients
      (24.5%) with complications had HBVDNA levels <10(4) copies/mL. The major factor
      for the development of cirrhotic complications was viral loads but cirrhotic
      complications continued to develop in patients with HBVDNA levels below 10(4)
      copies/mL.

PMID- 15985008
TI  - Pegylated interferon-alpha 2b-ribavirin combination in Egyptian patients with
      genotype 4 chronic hepatitis.
AB  - Egypt has a high prevalence rate of hepatitis C (HCV) infection and as much as
      90% is genotype 4. Response to interferon (IFN) varies with viral genotype and
      degree of fibrosis. Genotype 4 is poorly sensitive to standard IFN and IFN
      ribavirin combination. We evaluated pegylated interferon (PEG-IFN)-alpha2b in our
      patients. Sixty-one patients with compensated chronic HCV genotype 4 were
      enrolled in two groups: group A (31 patients) received IFN-alpha2b 3 MU three
      times per week and group B (30 patients) received 1.5 mug/kg PEG-IFN-alpha2b once
      weekly. Ribavirin was added to each regimen in a dose of 800-1200 mg based on
      body weight. Patients were followed up for 24 weeks to assess the sustained
      response (SR). End-of-treatment response (ETR) was achieved in 11 of 31 patients
      (35.48%) in group A, and 13 of 30 patients (43.33%) in group B (P < 0.05). Only
      eight patients in group A and 10 in group (B) achieved a sustained virological
      response (25.8 and 33.3%, respectively) (P < 0.05). By computing ETR, SR or
      relapse and pretreatment baseline data (pretreatment, viral load, alanine
      transaminases, necroinflammatory and hepatic fibrosis), both inter- and
      intragroup, no significant correlations could be detected. In terms of safety and
      tolerability, PEG-IFN-alpha2b and IFN-alpha2b were comparable. In spite of mild
      insignificant increase in ETR and SR with the pegylated form, the poor response
      of genotype 4 in Egypt (genotype 4a) to different forms of IFNs may be related to
      an intrinsic resistance to the direct antiviral effect of IFN.

PMID- 15985009
TI  - Determinants of early mortality and benefits of lamivudine therapy in patients
      with hepatitis B virus-related decompensated liver cirrhosis.
AB  - Chronic hepatitis B infection (HBV) is a major health problem worldwide. The
      prognosis is grave for patients with HBV-related decompensated liver cirrhosis
      (LC). We evaluated the effectiveness and the determinants of early mortality of
      lamivudine treatment in patients with HBV-related decompensated LC. Thirty
      patients with HBV-related decompensated LC and active viral replication were
      treated with lamivudine 100 mg daily for a median duration of 9 months. Among
      these patients, five patients died within 3 months. Two patients were lost to
      follow-up at week 8 and 9. One patient was treated for <6 months. Twenty-two
      patients were treated over 6 months. Univariate analysis revealed that the total
      bilirubin (P = 0.008), prothrombin time (P = 0.004), Child-Turcotte-Pugh score (P
      = 0.005), the model of efd-stage liver disease score (P = 0.004) and stage III
      hepatic encephalopathy (P = 0.001) were predictive factors of early mortality.
      Multivariate analysis revealed that the independent factor associated with early
      mortality was stage III encephalopathy. Among 22 patients, liver function
      improved markedly after lamivudine therapy. Of the nine hepatitis B e antigen
      (HBeAg)-positive patients, three had HBeAg seroconversion. Two patients had YMDD
      mutant and virological breakthrough at 41 and 46 weeks. One of the two had
      hepatocellular carcinoma and died of hepatic failure at week 125; the other
      received adefovir and is doing well. Lamivudine appeared to have benefits in
      viral suppression and significant improvement in liver function in patients with
      HBV-related decompensated LC. As noted in prior studies, poor baseline liver
      function is associated with a poor prognosis in Asian patients with decompensated
      HBV cirrhosis treated with lamivudine.

PMID- 15985010
TI  - Efficacy of lamivudine re-treatment for relapsed patients after an initial
      lamivudine therapy in HBeAg-positive chronic hepatitis B.
AB  - The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who
      relapse after HBeAg seroconversion with lamivudine has not been investigated. The
      aim of this study was to evaluate the efficacy of lamivudine re-treatment in
      relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with
      lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse
      occurred in 49 patients (40.5%). Thirty-three relapsed patients received
      lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re
      treatment was 16 months and the follow-up period was 8.9 months. HBeAg
      seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg
      seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively.
      The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than
      that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough
      occurred in six (18.2%) patients. All patients with viral breakthrough were
      accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15
      patients who discontinued lamivudine re-treatment after HBeAg seroconversion,
      relapse occurred in six patients (40%). All relapses occurred within 9 months
      after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine
      re-treatment in relapsed patients after initial lamivudine therapy had a higher
      response rate and shorter duration to HBeAg seroconversion than during the
      initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment
      was not durable.

PMID- 15985011
TI  - Response to long-term lamivudine treatment (up to 5 years) in patients with
      severe chronic hepatitis B, role of genotype and drug resistance.
AB  - Lamivudine is effective in suppressing viral replication, normalizing alanine
      aminotransferase (ALT), and improving histological appearance in HBe positive and
      negative hepatitis. It is unclear whether hepatitis B virus (HBV) genotype
      influences the response to lamivudine. We report the long-term response of
      patients with chronic hepatitis B with and without cirrhosis at baseline treated
      with lamivudine according to HBV genotype. Retrospective review of charts of all
      patients treated with lamivudine monotherapy between 1993 and 2002. Response to
      therapy defined as ALT in the normal range, undetectable HBV DNA, and in the
      HBeAg positive group loss of HBeAg and/or the development of anti-HBe. HBV DNA
      measured by the Digene Hybrid capture assay (sensitivity 1.4 x 10(6) copies/mL).
      YMDD mutation at rtL180M and rtM204V/I measured by restriction digest of
      amplified products. Genotyping performed by sequencing and phylogenetic tree
      analysis of the preS region of the virus genome. Seventy-one patients treated
      with lamivudine for 6 months or more, 53 (75%) were male, average age 47 years,
      38 (54%) were HBeAg+ and 33 (46%) HBeAg-. Mean baseline HBV DNA viral titre was
      1280.2 copies/mL and 518 copies/mL respectively. Cirrhosis was present in 30
      (42%). Sera were examined for YMDD mutations at last patient visit in 61 (86%),
      and were detected in 45 (74%), there being no association with a particular
      genotype. Data from up to 5 years on lamivudine indicated no difference in
      biochemical or virological response between genotypes. Cirrhosis was more
      prevalent with specific genotypes. We found no influence of HBV genotype on the
      development of resistance to lamivudine, however liver disease severity was
      influenced by genotype.

PMID- 15985012
TI  - Changing of hepatitis C virus genotype patterns in France at the beginning of the
      third millenium: The GEMHEP GenoCII Study.
AB  - This cross-sectional study aimed to investigate, during a short period between
      2000 and 2001, in a large population of patients with chronic hepatitis C, the
      epidemiological characteristics of hepatitis C virus (HCV) genotypes in France.
      Data from 26 referral centres, corresponding to 1769 patients with chronic
      hepatitis C were collected consecutively during a 6-month period. HCV genotyping
      in the 5'-non-coding region (NCR) was performed in each center using the line
      probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific
      polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non
      subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of
      our population, respectively. HCV genotype distribution was associated with
      gender, age, source and duration of infection, alanine aminotransferase (ALT)
      levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human
      immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the
      source of infection was the independent factor significantly associated with
      genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV
      genotypes in France, with i.v. drug abuse as the major risk factor, an increase
      of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b
      and 2. The modification of the HCV genotype pattern in France in the next 10
      years may require new therapeutic strategies, and further survey studies.

PMID- 15985013
TI  - Effect of IL-2 on hepatitis C virus RNA levels in patients co-infected with human
      immunodeficiency virus receiving HAART.
AB  - The effect of interleukin-2 (IL-2) on the plasma levels of hepatitis C RNA (HCV
      RNA) has varied in published reports. We measured the impact of IL-2 on plasma
      HCV RNA levels in 54 human immunodeficiency virus (HIV)/HCV coinfected patients
      enrolled in a randomized trial of 512 participants designed to compare the
      virologic and immunologic effects of cycled IL-2 plus antiretroviral therapy
      (ART) vs ART alone in the treatment of HIV in patients with CD4 cell counts > or
      =300 cells/mm(3). The mean decreases in average HCV RNA levels (copies/mL, log
      (10)) were 0.28 log in the IL-2 group (n = 26) and 0.04 log in the ART alone
      group (n = 28) at 12 months (P = 0.18). The changes in HCV RNA level were not
      associated with baseline or nadir CD4 cell counts, baseline aspartate
      aminotransferanse, CD4 cell response to IL-2, or changes in plasma HIV RNA
      values. Compared with those participants who only had HIV, the HIV/HCV co
      infected patients did not have a significantly different CD4 cell response to IL
      2 therapy. Intermittent IL-2 therapy does not produce a significant sustained
      decrease in plasma HCV RNA levels among patients co-infected with HIV/HCV who are
      on highly active ART.

PMID- 15985014
TI  - Safety and efficacy of peginterferon plus ribavirin in patients with chronic
      hepatitis C and bridging fibrosis or cirrhosis.
AB  - The combination of pegylated interferon and ribavirin is the most effective
      therapy in patients with chronic hepatitis C. We evaluated this combination in
      unselected patients with bridging fibrosis or cirrhosis. Eighty patients were
      treated with peginterferon alpha-2b plus ribavirin. Hepatitis C virus serum RNA
      was monitored. Tolerance and safety were evaluated by the rate of treatment's
      discontinuation for any reason, and occurrence of serious clinical adverse
      events, respectively. Sustained virologic response (SVR) rate was 36.3% overall,
      and was observed in every group of patients except those who had previously
      failed to respond to the combination of interferon and ribavirin. No serious
      clinical adverse event occurred. Treatment was withdrawn in 18.7% of patients.
      Variables associated with discontinuation of treatment were low prothrombin index
      [OR: 1.16 (1.05;1.27)] and low body mass index [OR: 1.47 (1.12;1.92)]. Initial
      blood count abnormalities were not associated with cessation of treatment.
      Furthermore, early virologic response at week 8 and week 12 of treatment had
      similar predictive value for SVR. Combination therapy with peginterferon plus
      ribavirin seems effective in this group of patients, except in those who had
      previously failed to respond to the combination of interferon and ribavirin. This
      therapy is safe with appropriate monitoring, but tolerance seems worse in
      patients with the most advanced liver disease.

PMID- 15985015
TI  - Liver enzymes elevation after HAART in HIV-HCV co-infection.
AB  - Hepatitis C virus (HCV) co-infection is common among human immunodeficiency virus
      (HIV) patients. The incidence and risk factors associated with hepatotoxicity in
      this population after high active antiretroviral therapy (HAART) is initiated are
      still not well-understood. We argued to evaluate the incidence and risk factors
      associated with liver enzyme elevation (LEE) and their clinical significance. A
      retrospective chart review of patients who started HAART and had follow up at our
      centre for at least 1 year was undertaken. The frequency and severity of alanine
      aminotransferase (ALT)/aspartate aminotransferase (AST) elevation after treatment
      initiation were investigated and searched for clinical manifestations. Between
      January 1996 and March 2002, 85 HIV-HCV co-infected patients began HAART and
      continued follow up for at least 1 year. The incidence of severe toxicity [grades
      3 + 4 LEE: >5 and >10 times the upper limit of normal (ULN) of ALT or AST] was
      calculated at 4% per person-years. There were no clinical manifestations of liver
      toxicity, and patients continued their treatment with a trend towards a decrease
      of their enzymes. No statistical differences in opportunistic infections or
      mortality were evident. The variables associated with severe hepatotoxicity were
      a higher baseline AST, higher international normalized ratio (INR) and lower
      albumin. A baseline AST < 2.1 ULN had a negative predictive value of 92% of
      leading to severe hepatotoxicity. In HIV-HCV co-infected patients therefore, the
      group at a higher risk of developing higher transaminase elevations is the one
      with a higher baseline AST, higher INR and lower albumin.

PMID- 15985016
TI  - SEN virus infection in patients with hepatocellular carcinoma.
AB  - Although most cases of hepatocellular carcinoma (HCC) are associated with either
      the hepatitis B or C viruses (HBV, HCV), about 10-20% of HCCs occur in patients
      with chronic hepatitis that is aetiologically undefined. The aim of the present
      study was to determine the prevalence of the transfusion-transmitted SEN virus
      (SEN-V) in patients with HCC, including those patients who do not otherwise
      appear to be infected with HBV or HCV. Fragments of SEN-V subtypes D and H were
      amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada
      and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues
      from eight of the Canadian patients. SEN-V DNA was found in the serum of 10 of 31
      (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of
      50 (36%) HCC patients]. SEN-V DNA was detected in the serum of 10 of 23 (43%) HCC
      patients with antibody to HCV (anti-HCV), six of 11 (55%) with hepatitis B
      surface antigen (HBsAg), and two of 16 (12%) without detectable anti-HCV or
      HBsAg. Twenty-three HCC patients in this study had 'silent HBV,' characterized by
      the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had
      SEN-V infections. SEN-V DNA was detected in HCC patients most typically in those
      with coexistent HBV or HCV infection. SEN-V was found in only one of seven HCC
      patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear
      to be an important cause of 'cryptogenic' HCC.

PMID- 15985017
TI  - Age-specific antibody to hepatitis E virus has remained constant during the past
      20 years in Japan.
AB  - We investigated the presence of antibodies to hepatitis E virus (anti-HEV) and
      hepatitis A virus (anti-HAV) by enzyme immunoassays in sera from 1015 individuals
      collected in 1974, 1984 and 1994. Age-specific profiles of anti-HEV remained
      unchanged with a peak at 40-49 years, while those of anti-HAV started to increase
      in individuals aged 20-29 years in 1974, 30-39 years in 1984 and 40-49 years in
      1994. These results suggest that a silent HEV infection has been taking place in
      the last 20 years or so in Japan, while HAV infection has been terminated at
      least since 1974.

PMID- 15985019
TI  - "Hidradenitis suppurativa" is acne inversa! An appeal to (finally) abandon a
      misnomer.
AB  - The term "hidradenitis suppurativa" is firmly entrenched in the dermatological
      literature although it refers to a false pathogenetic concept. The term was
      historically coined based merely on the characteristic distribution of the
      apocrine glands and the anatomical coincidence with the disease process. At
      center stage is not a suppurative inflammation of the apocrine sweat glands but
      an occlusion of the hair follicles, comparable to acne vulgaris. Reviewing the
      literature on this subject, we were astonished to find that even articles that
      concluded that the entity represents a form of follicular occlusion still
      referred to it as hidradenitis suppurativa. The disorder shares histopathological
      and clinical aspects with acne vulgaris modified under the special circumstances
      of anatomical regions rich in apocrine glands. It is acne inversa because, in
      contrast to acne vulgaris, the disease involves intertriginous localizations and
      not the regions classically affected by acne. We suggest that the term
      "hidradenitis suppurativa" for this disease should (finally) be abandoned in
      favour of "acne inversa".

PMID- 15985020
TI  - A comparison of anti-desmoglein antibodies and indirect immunofluorescence in the
      serodiagnosis of pemphigus vulgaris.
AB  - BACKGROUND: Indirect immunofluorescence (IIF) is the standard method for the
      detection of pemphigus autoantibodies. Commercially available enzyme-linked
      immunosorbent assays (ELISAs) have recently become available to measure serum
      antibodies (Abs) against desmoglein1 (Dsg1) and desmoglein3 (Dsg3). It has been
      suggested that patients with mucosal-dominant pemphigus vulgaris (PV) have serum
      Abs against Dsg3 only, patients with mucocutaneous PV have Abs to both Dsg1 and
      Dsg3, and patients with pemphigus foliaceus (PF) have Abs against Dsg1 only. AIM:
      To compare the sensitivity and specificity of the IIF and ELISA tests in the
      diagnosis of pemphigus and its subsets. METHODS: Thirty-three patients with PV
      and five patients with PF were studied, and compared with 50 healthy individuals
      or patients with unrelated skin diseases. Monkey esophagus was used as a
      substrate for the IIF test. RESULTS: The IIF and ELISA tests were each positive
      in 26 of the 32 (81%) PV patients, and in none (0%) and 3 (6%) of the 50
      controls, respectively. Both the IIF and ELISA results were concordant in 69% of
      the PV patients, and only one of these two tests was positive in the remaining
      31% of patients. Forty-six per cent of the PV patients with a positive ELISA test
      did not have the PV phenotype (mucosal or mucocutaneous) predicted by their
      autoantibody profile. CONCLUSION: The IIF and ELISA tests may be used as
      complementary tests for the serologic diagnosis of pemphigus.

PMID- 15985021
TI  - Rowell's syndrome revisited: report of two cases from India.

PMID- 15985022
TI  - Clinicopathologic review of 19 patients with systemic candidiasis with skin
      lesions.
AB  - BACKGROUND: A diagnosis of systemic candidiasis is often delayed or missed owing
      to the absence of sensitive, specific, and timely diagnostic tools. Skin lesions
      are not common, but they can help to rapidly establish a diagnosis. We report on
      a 14-year experience of systemic candidiasis with skin lesions in our
      institution. We report the prevalence, clinical findings, histologic findings,
      etiologic Candida species, underlying conditions, treatment modalities, and
      outcomes of the cases and compare them with the previous reports. METHODS: We
      reviewed the medical records and laboratory data of patients diagnosed with
      systemic candidiasis from June 1989 to September 2002 at Asan Medical Center,
      Seoul, Korea. We thoroughly reviewed the data on those patients with
      characteristic skin lesions. We included the cases in which Candida organisms
      were either shown or cultured from the skin. We also included the patients who
      had developed the characteristic rash at the onset of infection if there was no
      other possible explanation for the rash. RESULTS: Of 53 documented systemic
      candidiasis cases, 19 (35.8%) had the characteristic skin lesions. Fifteen
      patients (78.9%) had hematologic problems and were neutropenic. The skin lesions
      were a maculopapular or nodular rash and plaques. In addition to the trunk and
      proximal extremities, the rash also involved the face and distal extremities. The
      rashes were mostly purpuric, not consistently associated with underlying
      thrombocytopenia but also associated with underlying vascular damage as a result
      of Candida organisms. The underlying vascular damage also caused intraepidermal
      necrotic and vesicular change. One case of transepidermal elimination of
      organisms was newly found. The most common causative species was Candida
      tropicalis in the 19 patients with skin lesions, in contrast with Candida
      albicans in a total of 53 patients. The mortality rate was 84.2%. CONCLUSIONS:
      The prevalence of systemic candidiasis-associated skin lesions may be higher than
      previously reported. Dermatologists should be familiar with the clinical
      appearance of skin lesions and suspect this fatal infection when seeing
      neutropenic patients with a resistant fever and accompanying rash.

PMID- 15985023
TI  - Response of vitiligo to PUVA therapy in Saudi patients.
AB  - BACKGROUND: Vitiligo is not uncommon in southern Saudi Arabia. The response of
      Saudi patients to PUVA therapy has not been previously assessed. The aim of this
      study was to evaluate this response. METHODS: This is a retrospective study for
      the period of 1990-2001 in which 32 patients were included: Data were collected
      from the patients' records, including: age, sex, age at onset of disease, type of
      vitiligo, cumulative dose, maintenance dose, total number of sessions, number of
      sessions to induce pigmentation, treatment duration, and response rate. RESULTS:
      The overall response rate was 59.4%. The most sensitive sites were the face,
      trunk, arms, and legs, while the most resistant sites were the hands, feet, and
      perioroficial areas (perioral and periorbital). Acute complications occurred in
      59.4%, while chronic complications occurred in 78.1%. Analysis of the factors
      that affect the response rate showed that age, sex, the disease duration, and the
      treatment duration did not affect the response rate, while the surface area and
      the number of sessions to induce pigmentation showed a positive relation.
      CONCLUSIONS: PUVA is still considered as the most appropriate and effective
      treatment for vitiligo. Saudi patients showed good response to treatment in
      general. Some sites such as the face, trunk, arms, and legs showed sensitivity to
      therapy, while hands, feet, and periorificial areas showed resistance to therapy.
      Generalized type was the best type to respond, followed by the periorificial
      type. Acral and segmental types were very resistant to therapy.

PMID- 15985024
TI  - Mycosis fungoides and Sezary syndrome: therapeutic approach and outcome in 113
      patients.
AB  - BACKGROUND: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common
      forms of cutaneous T-cell lymphoma (CTCL). Various topical and systemic
      therapeutic alternatives are available, but there is no standard or definite
      curative treatment regimen. When making a decision about the appropriate
      treatment modality, the age and compliance of the patient, stage of the disease,
      treatment accessibility, and previous treatment history should be considered.
      AIM: To determine the therapeutic response of patients with MF and SS to
      different treatment modalities. Patients were evaluated with respect to their
      clinical and demographic features. METHODS: One hundred and thirteen patients
      diagnosed clinically and dermatopathologically with MF and SS between March 1984
      and June 2001 were included in the study. RESULTS: Of the 113 patients studied,
      110 had a diagnosis of MF and three had a diagnosis of SS; 101 patients (89.4%)
      were diagnosed with early stage (IA, IB, IIA) and 12 (10.6%) with late stage
      (IIB, III, IVA, IVB) disease. The age at diagnosis varied between 12 and 81 years
      (mean, 45.6+/-15.8 years). Fifty-five (48.7%) patients were male and 58 (51.3%)
      were female. The duration of the skin lesions varied between 1.5 months and 32
      years (mean, 6.1 years). Psoralen plus UVA (PUVA) was the most commonly used
      initial treatment modality in early stage disease (91%), with a complete
      remission (CR) rate of 80.4%. With PUVA+interferon-alpha (INF-alpha) treatment,
      CR was 57% in the early stages and 33.3% in the late stages. For late stage
      disease, systemic therapies, such as pentostatin, gemcitabine, and fludarabine,
      alone or in combination with INF-alpha, were preferred. Of the 113 patients,
      eight (7% of the total and 57.1% of the advanced stage cases) died of MF; 21.4%
      of the late stage patients showed partial remission and 14.2% showed CR. None of
      the patients diagnosed with early stage disease died of MF, but two (1.9%)
      progressed to late stage disease. CONCLUSIONS: PUVA and PUVA+INF-alpha are
      effective treatment modalities, especially for early stage MF. Once the disease
      has progressed, both MF and SS are very resistant to treatment regimens,
      including chemotherapeutic agents. It is important to diagnose and treat these
      diseases, especially MF, in the early stages for lasting remission.

PMID- 15985025
TI  - Lucio's phenomenon: a case report and review of the literature.

PMID- 15985026
TI  - Successful treatment of extensive basidiobolomycosis with oral itraconazole in a
      child.
AB  - BACKGROUND: Basidiobolomycosis is a rare chronic subcutaneous infection caused by
      Basidiobolus ranarum, which is usually treated with potassium iodide. Extensive
      deforming lesions in children can occur owing to lack of early diagnosis and/or
      inappropriate treatment. CASE REPORT: An 8-year-old girl child presented to us
      with extensive deforming plaque-like lesions over the left thigh and leg with
      multiple ulcerations of 1 year's duration. Histopathology was suggestive of
      subcutaneous zygomycosis with Splendore Hoeppli phenomenon. Microscopic
      examination of the tissue showed branching, sparsely septate fungal hyphae on a
      10%KOH mount, and culture yielded Basidiobolus ranarum. The patient was initially
      treated with potassium iodide for 6 weeks to which only a poor response was
      observed. Itraconazole therapy resulted in rapid regression of the lesions and
      complete resolution after 15 weeks of therapy. She continues to be disease-free
      at 1 year of follow up. CONCLUSIONS: This case report highlights that in an older
      child even longstanding extensive basidiobolomycosis can be safely treated with
      itraconazole. Surgery is not usually necessary in these patients.

PMID- 15985027
TI  - Evolution of histoid leprosy (de novo) in lepromatous (multibacillary) leprosy.

PMID- 15985028
TI  - Destructive facial T-cell lymphoma: the difficulty in diagnosis of pyoderma-like
      processes.

PMID- 15985029
TI  - Segmental neurofibromatosis of facial localization.

PMID- 15985030
TI  - Warty and clear cell Bowen's disease.

PMID- 15985031
TI  - Klebsiella oxitoca folliculitis mimicking tinea barbae in a diabetic man.

PMID- 15985032
TI  - Evaluation of the efficacy of ciclopirox 0.77% gel in the treatment of tinea
      pedis interdigitalis (dermatophytosis complex) in a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Ciclopirox is an antifungal agent and is effective against both Gram
      positive and Gram-negative bacteria. These properties may give ciclopirox an
      advantage over other antifungal agents in the treatment of interdigital tinea
      pedis with secondary bacterial infection (dermatophytosis complex). OBJECTIVE: To
      evaluate the efficacy of ciclopirox 0.77% gel in the treatment of tinea pedis
      interdigitalis with secondary bacterial infection in a prospective, randomized,
      double-blind, placebo-controlled clinical study. SUBJECTS AND METHODS: One
      hundred subjects were enrolled in this 8-week study (twice-daily ciclopirox, 40
      subjects; once-daily ciclopirox, 40 subjects; twice-daily vehicle, 20 subjects).
      Mycologic sampling, bacterial swabs, and evaluations for symptoms and signs of
      tinea pedis were performed on a target webspace at baseline and at weeks 2, 4,
      and 8. Global evaluations were made by both investigator and subject at each
      visit. RESULTS: Ciclopirox gel applied once or twice daily significantly reduced
      the signs and symptoms at week 8, compared with vehicle (P<0.0036). The mycologic
      cure and complete cure rates were much higher for the ciclopirox regimens than
      for the vehicle regimen. Early reduction of bacterial counts was noted with the
      ciclopirox regimens. There was no significant difference in the adverse event
      rate between the ciclopirox groups and the placebo group. CONCLUSION: Ciclopirox
      0.77% gel, applied once or twice daily, is effective and safe in the treatment of
      tinea pedis interdigitalis with concomitant bacterial infection (dermatophytosis
      complex).

PMID- 15985033
TI  - Anticonvulsant hypersensitivity syndrome.

PMID- 15985034
TI  - 4% hydroquinone versus 4% hydroquinone, 0.05% dexamethasone and 0.05% tretinoin
      in the treatment of melasma: a comparative study.

PMID- 15985035
TI  - Lucio's phenomenon/erythema necroticans.
AB  - Lucio's phenomenon/erythema necroticans is a peculiar reaction pattern that
      occurs in untreated pure primitive diffuse lepromatous leprosy (PPDL) and/or
      relapsing leprosy recognized as spotted leprosy of Lucio. The small number of
      reported cases in the world literature suggests that it is fairly uncommon. Its
      clinical features are fairly characteristic and consist of extensive, bizarre,
      painful ulcerations of the skin, with constitutional symptoms being conspicuous
      by their absence. The clinical diagnosis is confirmed by microscopic pathology
      marked by proliferation and mobilization of polyblasts and histiocytes,
      dilatation, endothelial proliferation, luminal occlusion, and thrombosis of the
      superficial and mid-dermal blood vessels and demonstration of acid-fast bacilli
      in the blood vessel walls. Its precise pathogenesis is still unclear, but is
      believed to occur either through the usual or the alternate pathway of complement
      activation in the natural history of erythema nodosum leprosum. The clinical and
      immunological features of reactions in leprosy, including erythema nodosum
      leprosum, are well known and have been critically evaluated elsewhere.

PMID- 15985036
TI  - On the diagnosis of facial granulomatous dermatoses of obscure origin.

PMID- 15985037
TI  - Disseminated cutaneous leishmaniasis on lymphedema following radiotherapy.

PMID- 15985038
TI  - Acquired immunodeficiency syndrome-related Kaposi's sarcoma of the axilla and
      breast after percutaneous intravenous catheter insertion.

PMID- 15985039
TI  - Healing effect of garlic extract on warts and corns.

PMID- 15985040
TI  - Thromboangiitis obliterans associated with peripheral blood and eosinophilic
      cellulitis-like skin lesions.

PMID- 15985041
TI  - Letter to the editor.

PMID- 15985043
TI  - A second (non-genomic) steroid mechanism of action: possible opportunity for
      novel pharmacotherapy?

PMID- 15985044
TI  - Current concepts in the endocrine therapy of breast cancer: tamoxifen and
      aromatase inhibitors.
AB  - Recent results from randomized controlled trials have indicated that aromatase
      inhibitors have superior anticancer efficacy and toxicity profiles compared with
      tamoxifen in the treatment of post-menopausal women with node-negative hormone
      receptor positive breast cancer. This has led clinicians to question whether
      adjuvant tamoxifen therapy is still justified. This article discusses the
      evidence for the superiority of aromatase inhibitors over tamoxifen. There are
      limitations to the use of these drugs, and they have side effects, which require
      further clarification. In addition, there are certain niche advantages to the use
      of tamoxifen, and this drug has undergone rigorous appraisal over the last 20
      years.

PMID- 15985045
TI  - Pharmacokinetics and pharmacodynamics profiles of enalapril maleate in healthy
      volunteers following determination of enalapril and enalaprilat by two specific
      enzyme immunoassays.
AB  - BACKGROUND AND OBJECTIVES: Most of the pharmacokinetic (PK) parameters for
      enalapril and enalaprilat were established following determination of the drug
      and its metabolite, using angiotensin converting enzyme (ACE) inhibition assays.
      In these methods, enalapril has to be hydrolysed to enalaprilat first and then
      assayed. The purpose of this study was to re-estimate the PK parameters of
      enalapril and enalaprilat in healthy volunteers using two specific enzyme
      immunoassays for enalapril and enalaprilat. METHODS: The rate and extent of
      absorption of enalapril and enalaprilat from a 10-mg dose of two enalapril
      maleate commercial brands (Renetic and Enalapril) were estimated using a two-way
      cross over design with 1-week washout period. Blood pressure was also measured at
      specified time intervals and correlated to enalaprilat plasma concentrations.
      RESULTS: For enalapril, the AUC(o-->infinity) values (Mean+/-SD) were 450.0+/
      199.5 and 479.6+/-215.6 ng h/mL, Cmax values were 313.5+/-139.6 and 310.1+/-186.6
      ng/mL, Tmax values were 1.06+/-0.30 h and 1.13+/-0.22 h, and t1/2 ranged between
      0.3 to 6.1 h (1.6+/-1.5) and 0.40 to 5.05 h (1.3+/-1.0), for the two brands. For
      enalaprilat, the AUC(o-->infinity) values were 266.9+/-122.7 and 255.9+/-121.8 ng
      h/ml, Cmax values were 54.8+/-29.5 and 57.2+/-29.0 ng/mL, Tmax values were 4.6+/
      1.6 h and 4.3+/-1.45 h, and t1/2 ranged between 1.1 to 10.5 h (4.5+/-2.9) and 0.6
      to 9.4 h (3.5+/-2.5) for the two brands. CONCLUSIONS: Cmax values for enalapril
      are about 10 times those published in the literature and the rate and extent of
      absorption of the two brands of enalapril and their deesterification to
      enalaprilat following the administration of either brand were bioequivalent.
      Secondly, enalaprilat concentrations at 12-24 h following a single oral dose of
      enalapril in healthy volunteers were lower than those reported in the literature.
      The values reported here correlated with the return of blood pressure to predose
      level. Thirdly, enzyme immunoassays for enalapril and enalaprilat are better than
      ACE inhibition assays and can be used in bioequivalence assessment of enalapril
      and enalaprilat and for therapeutic drug monitoring in a clinical laboratory
      setting.

PMID- 15985046
TI  - Controlling the proliferation of Zygosaccharomyces bailii in ephedrine anti
      phlegm cough mixture.
AB  - BACKGROUND AND OBJECTIVE: To explain a reported proliferation of
      Zygosaccharomyces bailii in a commercially available ephedrine anti-phlegm cough
      mixture preserved with 0.1% sodium benzoate, and to present a strategy for
      controlling its growth. METHODS: A yeast strain was isolated from the cough
      mixture and identified using biochemical tests, selective media and 18S rDNA
      sequencing. Preservative minimum inhibitory concentrations (MICs) were determined
      based on the broth microdilution technique. The cough mixture was reproduced
      using benzoate and a number of other candidate preservatives. Bottles were
      challenged with the yeast using the test for antimicrobial efficacy outlined in
      the monographs of the European Pharmacopoeia. RESULTS: The contaminating yeast
      was identified as Z. bailii. The yeast MIC value for benzoate was close to or
      above the concentration used in the commercially available cough mixture.
      Reintroduction of the strain into bottles preserved with benzoate or sorbate,
      gave an initial reduction in the inoculum concentration (>1 log) followed by
      growth to values close to those found in the contaminated product. Furthermore,
      yeast cells taken from bottles at the end of the challenge test, suffered no
      initial reduction in numbers and grew in fresh bottles of the product, possibly
      suggesting adaptation to weak-acid preservatives. Two paraben-based preservative
      systems passed the challenge test. CONCLUSION: Preservatives of the weak-acid
      type do not control the growth of Z. bailii in ephedrine cough mixture for
      reasons discussed in this article. If the raw juice used in production of the
      product cannot be treated to eliminate the yeast, other preservatives must be
      sought. We show that paraben-based systems are effective in this role, and these
      are discussed as possible replacements for benzoate in the cough mixture.

PMID- 15985047
TI  - Motivations and perceived influences on rural and urban general practitioners
      when prescribing conventional non-steroidal anti-inflammatory drugs or COX-2
      inhibitors.
AB  - BACKGROUND AND OBJECTIVE: Prescribers in rural and remote locations perceive that
      there are different influences on their prescribing compared with those
      experienced by urban prescribers. The aim of this study was to compare the
      motivations and perceived influences on general practitioners (GPs) when
      prescribing COX-2 inhibitors rather than conventional non-steroidal anti
      inflammatory drugs (NSAIDs) between rural and urban-based GPs in Queensland,
      Australia. METHODS: A questionnaire was administered to two geographically
      distinct groups of GPs, one urban (n=67) and one rural (n=67), investigating the
      reasons that the GP would prescribe a COX-2 inhibitor rather than a conventional
      NSAID or vice versa and also focusing on patients requesting a prescription for a
      COX-2 inhibitor. RESULTS AND DISCUSSION: A 51% response rate (n=68) was achieved.
      The difference between the rural and the urban GPs was that the urban GPs were
      more likely to perceive that they were influenced to prescribe COX-2 inhibitors
      by their patients' knowledge of these new (at the time) drugs. GPs in both the
      rural and urban areas perceived the COX-2 selective inhibitors to be safer than
      conventional NSAIDs, and that there was little difference in terms of efficacy
      between the two drug classes. However, GPs from both of the study areas stated
      that conventional NSAIDs were preferred over COX-2 selective inhibitors,
      primarily due to their expense, if their patients were not at risk for developing
      a GI bleed. CONCLUSION: The motivations and perceived influences to prescribe a
      COX-2 inhibitor in rural and in urban areas of Queensland, Australia were very
      similar. Almost all surveyed GPs in rural and urban areas had patients request a
      prescription, or enquire about the COX-2 inhibitors. Urban GPs were more likely
      to feel pressured to prescribe a COX-2 inhibitor than their rural counterparts,
      agreeing with other research which found that patient pressure to prescribe
      appears to be greater in urban general practice.

PMID- 15985049
TI  - Health-related quality of life in hypertension: impact of a pharmacy intervention
      programme.
AB  - BACKGROUND AND OBJECTIVE: In a previous study, we observed that a pharmacy-based
      intervention programme decreased the blood pressure of hypertensive patients. The
      objective of the present study was to assess the effect of this pharmacy
      programme on the health-related quality of life (HRQOL) of individuals treated
      for hypertension. METHODS: In a quasi-experimental cohort pilot study, we
      recruited 91 participants from nine pharmacies in the Quebec City area. We
      offered the intervention programme over a 9-month period to participants enrolled
      at four of the pharmacies. The other participants were not exposed to
      pharmaceutical services other than those usually given by their pharmacists. We
      used the SF-36 to evaluate HRQOL. Covariance analysis was used to test for
      significant differences of HRQOL scores between participants exposed and not
      exposed to the programme. RESULTS AND DISCUSSION: When compared with the non
      exposed participants, those receiving the intervention and with high income had
      an improvement in vitality score (P=0.05). On the contrary, low-income exposed
      participants did not show this benefit and had a decline in mental health score
      (P=0.01). Improvement in vitality is likely due to increased physical activity
      and to a reduction in systolic blood pressure in the high-income exposed group.
      The negative effect of the programme on the mental health of those exposed in the
      low-income group might be due to the fact that the programme was not effective in
      reducing blood pressure and may therefore have caused anxiety. CONCLUSION:
      Pharmacists' interventions can have both a positive and negative impact on the
      HRQOL of individuals, treated with antihypertensive agents, depending on income
      level.

PMID- 15985048
TI  - Improving the outcomes of anticoagulation in rural Australia: an evaluation of
      pharmacist-assisted monitoring of warfarin therapy.
AB  - OBJECTIVE: The aim of this project was to assess whether rural pharmacist
      involvement in the management of patients receiving warfarin has the potential to
      lead to safer and more effective anticoagulation, and is valued and welcomed by
      patients and their general practitioners (GPs). METHODS: A convenience sample of
      rural pharmacists was trained in the use of the CoaguChek S International
      Normalized Ratio (INR) monitor and then conducted pharmacy-based testing for
      approximately 3 months. Two types of testing were performed in the pharmacy: (i)
      comparison testing was defined as pharmacy-based tests taken within 4 h of
      conventional laboratory testing or (ii) additional testing, which was a pharmacy
      based test with no direct comparison laboratory test taken. Pharmacists, GPs and
      patients completed anonymous satisfaction surveys after the completion of the
      pharmacy-based testing. RESULTS: Pharmacists from 16 rural pharmacies were
      trained to use the CoaguChek S monitor. During the trial period, 518 INR tests
      were performed in the pharmacies on 137 different patients. A total of 120 tests
      were evaluated against results from laboratory testing. The pharmacy-based INR
      values were significantly correlated with the laboratory INR values (mean of
      2.32+/-0.77 and 2.32+/-0.59 respectively; r=0.88, P<0.0001). A total of 398
      additional pharmacy-based tests were conducted in the pharmacy and 8.5% of the
      additional tests resulted in a subsequent dosage change. The monitoring was well
      received by pharmacists, GPs and patients. CONCLUSIONS: The results of the trial
      were very positive. The CoaguChek S monitor in pharmacy-based testing performed
      accurately compared with conventional laboratory testing. Further research needs
      to be conducted on the impact of community pharmacy-conducted INR monitoring on
      patient care and outcomes.

PMID- 15985050
TI  - Echinacea intake induces an immune response through altered expression of
      leucocyte hsp70, increased white cell counts and improved erythrocyte antioxidant
      defences.
AB  - OBJECTIVE: To study the effect of Echinacea tablets on the expression of
      leucocyte heat shock protein 70 (hsp70), erythrocyte haemolysis, plasma
      antioxidant status, serum chemistry, haematological values and plasma alkylamide
      concentrations. METHOD: Eleven healthy individuals (26-61 years of age) were
      evaluated at baseline (day 1) and on day 15 after consuming two commercially
      blended Echinacea tablets daily for 14 days. RESULTS: Echinacea supplementation
      enhanced the fold increase in leucocyte hsp70 expression after a mild heat shock
      (P=0.029). White cell counts (WCC) were also increased (P=0.043). We also
      observed a preventative effect against free radical induced erythrocyte
      haemolysis (P=0.006) indicative of an antioxidant effect. CONCLUSION: The pilot
      study suggests that Echinacea may invoke an immune response through altered
      expression of hsp70 and increased WCC.

PMID- 15985051
TI  - An evaluation of antimicrobial prophylaxis in paediatric surgery and its
      financial implication.
AB  - OBJECTIVE: To assess the appropriateness of use of antimicrobial prophylaxis in
      paediatric surgery in Singapore. METHODS: A prospective evaluation of the use of
      antimicrobial prophylaxis in paediatric patients undergoing surgery in KK
      Hospital, Singapore was carried out from September and December 2001. Process
      measures for the study included adherence to local or international guidelines,
      choice and dose of antimicrobial agent and timing and duration of prophylaxis.
      Outcome measures included surgical site and other related infections. A cost
      analysis was also performed to look at the extra expenditure due to any excessive
      use of antimicrobials. RESULTS: A total of 171 patients with a mean age of 5.7
      years (SD=4.5) were included in the study. Among the 117 (68.4%) elective and 54
      (31.6%) emergency procedures, 22 cases (12.8%) were fully compliant with the
      guidelines. The most frequently encountered non-compliance types were unnecessary
      prolongation of prophylaxis (54.4%), inappropriate choice of antibiotics (42.7%)
      and overdose of antibiotics (26.3%). The estimated extra cost to patients for the
      study period was Sing$13,879.41 (US 8164.36). CONCLUSION: The results showed a
      significantly high level of inappropriate use of antimicrobial prophylaxis in
      paediatric surgery in Singapore. However, when the individual factors such as
      appropriate choice of antibiotics, appropriate timing and duration were
      considered, the situation was very similar to the results obtained from overseas
      studies.

PMID- 15985052
TI  - Penetration of ciprofloxacin and its desethylenemetabolite into skin in humans
      after a single oral dose of the parent drug assessed by cutaneous microdialysis.
AB  - OBJECTIVE: To measure the concentration of ciprofloxacin and its
      desethylenemetabolite in plasma and cutaneous microdialysates and to compare
      ciprofloxacin penetration into cutaneous microdialysates against theoretically
      predicted penetration in a peripheral compartment. METHOD: A single oral dose of
      0.5 g of the parent drug was administered to 10 healthy male volunteers.
      Microdialysis probes with 2 kDa molecular weight cut-off were inserted
      intradermally and were perfused with Ringer solution up to 8 h after drug
      ingestion. Drug and metabolite concentrations were measured by high performance
      liquid chromatography. RESULTS: Mean maximum concentrations of ciprofloxacin in
      plasma, cutaneous microdialysates and theoretical peripheral compartment were
      7.01+/-1.69, 2.95+/-0.64 and 3.37+/-0.60 micromol/L, respectively, and were
      achieved after about 2.0+/-0.6, 2.4+/-0.9 and 4.8+/-0.9 h. The extent of
      penetration into cutaneous microdialysates and theoretical peripheral compartment
      relative to plasma were 0.550+/-0.150 and 0.788+/-0.131, respectively, and
      differed significantly. Similarly, time to maximum concentration as well as area
      under the concentration-time curve in these compartments also differed
      significantly unlike the maximum concentration. CONCLUSION: Microdialysis permits
      the evaluation of the penetration of drug and its metabolites into target
      tissues. Such evaluation is helpful to optimize treatment strategies. After a
      single 0.5 g oral dose, ciprofloxacin penetrated into skin and achieved
      concentrations above the minimum inhibitory concentrations for susceptible
      pathogens, recommended by the National Committee for Clinical Laboratory
      Standards (NCCLS).

PMID- 15985053
TI  - Queen Mary Utilization of Antihypertensive Drugs Study: side-effects of
      antihypertensive drugs.
AB  - BACKGROUND AND OBJECTIVE: Effective prevention of cardiovascular events in
      hypertensive patients requires good control of blood pressure. Side-effects of
      antihypertensive drugs affect tolerability and compliance. Accordingly, we
      surveyed side-effects in the hypertension outpatient clinic. METHODS: A total of
      228 patients (109 men, 119 women) were interviewed in April-May 2004 in the Queen
      Mary Utilization of Antihypertensive Drugs Study. RESULTS: The percentage of
      patients receiving no drug (life-style modification), one, two, three and over
      three drugs were 3, 30, 40, 22 and 6% respectively. The proportion of patients
      taking calcium channel blockers, beta-blockers (BB), angiotensin-converting
      enzyme inhibitors, thiazide diuretics, alpha-blockers and angiotensin receptor
      blockers were 65, 64, 33, 24, 4 and 7% respectively. Blood pressure on treatment
      was 144+/-21/82+/-11 mmHg. Among patients on antihypertensive drug therapy, 34%
      reported adverse effects: dizziness (9%), ankle swelling (7%), headache (5%),
      fatigue (4%), chest discomfort (3%) and cough (3%). Fewer patients on BBs
      reported side-effects (OR 0.46, P=0.008). The likelihood of experiencing side
      effects was unrelated to sex, age, weight, BMI, years of treatment, number of
      drugs used, heart rate on treatment or compliance. CONCLUSIONS: To achieve good
      blood pressure control, multiple drugs are used. Thiazides are underused whereas
      BBs are popular. The popularity of the latter may be related to its tolerability.

PMID- 15985054
TI  - Population pharmacokinetic investigation of disopyramide by mixed effect
      modelling using routine clinical pharmacokinetic data in Japanese patients.
AB  - OBJECTIVE: To estimate the population pharmacokinetic parameters of disopyramide
      using non-linear mixed effects modelling. METHOD: A total of 148 serum levels
      from 109 patients (61 males and 48 females) receiving disopyramide were
      collected. RESULTS: The final pharmacokinetic model was Cl
      (L/h)=3.75.TBW0.567.AGE-0.374.Conc(-0.719).1.48(DOSE>or=5), Vd (L/kg)=4.13 and
      k(a) (h-1)=0.363, where Cl is total body clearance, Vd is apparent volume of
      distribution, k(a) is absorption rate constant, TBW is total bodyweight (kg), AGE
      is age (years), Conc is the concentration of disopyramide (microg/mL), and
      DOSE>or=5=1 for patient received 5 mg/kg/day of disopyramide dosage or over and 0
      otherwise. CONCLUSION: Application of the findings in this study to patient care
      may permit selection of an appropriate initial maintenance dosage to achieve
      target disopyramide concentrations and the desired therapeutic effect.

PMID- 15985055
TI  - Appropriate dosing regimen of allopurinol in Japanese patients.
AB  - OBJECTIVE: Approved dosage regimens for prescription drug products are developed
      with a view to obtaining a favourable therapeutic index in the overall exposed
      population. The purpose of this study was to examine differences between the
      approved dosage regimen and the clinically prescribed doses of allopurinol in
      major hospitals in Japan. METHODS: The prescribing records for allopurinol were
      scrutinized at five national hospitals in Japan. Prescription information,
      including mean dose and the distribution of doses, was extracted for each
      hospital and the data compared with the dosage recommended in the approved
      labelling for the product. In addition, therapeutic drug monitoring (TDM) data
      were examined to evaluate relationships between dose administered, serum
      concentration of oxypurinol, and clinical efficacy. RESULTS: The mean dose of
      allopurinol prescribed in the five institutions, 131.7 mg/day, was lower than the
      approved dosage of 200-300 mg/day. There were no differences in the mean dose
      between the hospitals, and similar dose distributions were seen among the
      hospitals. Approximately 60-70% of patients were treated with 100 mg/day and 20
      30% with 200 mg/day of allopurinol. The most frequent dosage of allopurinol used
      in clinical practice was 100 mg/day. In the TDM study, the mean trough serum
      concentrations of oxypurinol were 9.5+/-3.6 microg/mL (50 mg/day), 13.0+/-6.8
      microg/mL (100 mg/day), 19.8+/-12.9 microg/mL (200 mg/day) and 15.7+/-7.3
      microg/mL (300 mg/day). The mean values of creatinine clearance were 17.0+/-16.4
      mL/min (50 mg/day), 33.5+/-32.8 mL/min (100 mg/day), 57.8+/-33.8 mL/min (200
      mg/day) and 94.3+/-35.8 mL/min (300 mg/day, in patients with normal renal
      function), and showed a downward trend together with a reduction of dosage of
      allopurinol. Allopurinol was given to 91% (91/100) of patients at a daily dose of
      100-200 mg, and the oxypurinol trough serum concentration attained (>4.6
      microg/mL) was sufficient to maintain a therapeutic effect in 92.3% (84/91) of
      these patients. A daily dose of 100-200 mg may be enough to obtain therapeutic
      serum oxypurinol concentrations in most Japanese patients. CONCLUSIONS: Dose of
      100-300 mg/day was an effective and commonly used dosing regimen for allopurinol
      in Japanese patients. The approved dosage range (200-300 mg/day) may be too high
      for patients with renal dysfunction, suggesting the recommended dosing regimen
      for allopurinol should be revised to include the lower doses.

PMID- 15985056
TI  - Possible azithromycin-associated hiccups.
AB  - OBJECTIVE: To report a case of persistent hiccups associated by azithromycin
      therapy. CASE SUMMARY: A 76-year-old man presented with persistent hiccups after
      beginning azithromycin for the treatment of pharyngitis. Hiccups were persistent
      and exhausting. Discontinuation of azithromycin and therapy with baclofen finally
      resolved hiccups. No organic cause of hiccups was identified despite extensive
      investigation. DISCUSSION: Pharmacotherapeutic agents have been uncommonly
      associated with hiccups. Corticosteroids (dexamethasone and methylprednisolone),
      benzodiazepines (midazolam) and general anaesthesia have been the specific agents
      mentioned most frequently in the literature as being associated with the
      development of hiccups. Few cases of drug-induced hiccups have been reported
      related to macrolide antimicrobials. Using the Naranjo adverse effect reaction
      probability scale this event could be classified as possible (score 5 points),
      mostly because of the close temporal sequence, previous reports on this reaction
      with other macrolides and the absence of any alternative explanation for hiccups.
      Our hypothesis is that a vagal mechanism mediated by azithromycin could be the
      pathogenesis of hiccups in our patient. CONCLUSIONS: Diagnosis of drug-induced
      hiccups is difficult and often achieved only by a process of elimination.
      However, macrolide antimicrobials have been reported to be associated with
      hiccups and vagal mechanism could explain the development of this side-effect.

PMID- 15985057
TI  - Global analysis of endothelial cell line proliferation patterns based on nutrient
      depletion models: implications for a standardization of cell proliferation
      assays.
AB  - It is known that cell populations growing in different environmental conditions
      may exhibit different proliferation patterns. However, it is not clear if,
      despite the diversity of the so-observed patterns, inherent cellular growth
      characteristics of the population can nevertheless be determined. This study
      quantifies the proliferative behaviour of the permanent endothelial human cell
      line, Eahy926, and establishes to which extent the estimation of the cell
      proliferation rate depends on variations of the experimental protocols. Cell
      proliferation curves were obtained for cells cultured over 16 days and the
      influences of cell seeding densities, foetal bovine serum content and frequency
      of culture medium changes were investigated. Quantitative dynamic modelling was
      conducted to evaluate the kinetic characteristics of this cell population. We
      proposed successive models and retained a nutrient-depletion toxicity dependant
      model, which takes into account the progressive depletion of nutrients, as well
      as the increase of toxicity in the cell culture medium. This model is shown to
      provide a very good and robust prediction of the experimental proliferation
      curves, whatever are the considered frequency of culture medium changes and serum
      concentrations. Thus, the model enables an intrinsic quantification of the
      parameters driving in vitro EAhy926 proliferation, including proliferation,
      nutrient consumption and toxicity increase rates, rather independently of the
      experiments design. We therefore propose that such models could provide a basis
      for a standardized quantification of intrinsic cell proliferation kinetics.

PMID- 15985058
TI  - Hepatic proliferation in Gunn rats transplanted with hepatocytes: effect of
      retrorsine and tri-iodothyronine.
AB  - Hepatocyte transplantation would offer an attractive alternative to liver
      transplantation in the treatment of inborn errors of liver metabolism. However, a
      major problem in most transplantation studies to date has been the limited growth
      of transplanted cells in the recipient organ. We performed a strategy for
      selective proliferation of transplanted cells by interfering with the
      proliferative capacity of resident hepatocytes, using the pyrrolizidine alkaloid
      retrorsine and then transplanting liver cells in conjunction with repeated
      administration of triiodothyronine, an inducer of hepatocyte proliferation in
      rats. In the present study, foetal and adult syngeneic hepatocyte transplantation
      into spleen was performed in retrorsine-treated hyperbilirubinemic Gunn rats. In
      parallel, repeated injections of triiodothyronine were given to recipients. Rats
      were sacrificed at 1, 7, 30 and 90 days after transplantation and blood and bile
      samples were taken to assess the functionality of transplanted cells. The
      proliferative activity of transplanted hepatocytes was evaluated using
      proliferating cell nuclear antigen labelling index. In summary, both adult and
      foetal hepatocyte transplantation were effective in correcting a metabolic
      abnormality in Gunn rats for as long as 3 months. The RS/T3 model, as a measure
      to increase graft function, could represent an important advance to future
      clinical application of hepatocyte transplantation.

PMID- 15985059
TI  - Circadian variation of the cell proliferation in the jejunal epithelium of rats
      at weaning phase.
AB  - Circadian variation in cell proliferation of the jejunal epithelium of 18-day-old
      rats was studied using the 2-h arrested metaphase score and crypt isolation
      method. A continuous decrease in the arrested metaphases occurred from 07.00 h to
      13.00 h. From 17.00 h arrested metaphase values increased and were maintained at
      the higher level during the dark period as showed by Cosinor analyses (P < 0.05).
      These results indicate that in the young rat there is already a circadian
      variation in jejunal epithelial cell proliferation as early as 18 days. We can
      even suggest that the presence of a circadian rhythm at weaning contributes to
      the steady state of cell proliferation in the intestinal epithelium observed in
      adult life.

PMID- 15985060
TI  - Effects of ultra-wideband electromagnetic pulses on pre-neoplastic mammary
      epithelial cell proliferation.
AB  - Electromagnetic ultra-wideband pulses (UWB) or nanopulses, are generated by a
      wide range of electronic devices used in communications and radar technology.
      However, the specific effects of nanopulse exposure on cell growth and function
      have not been extensively investigated. Here, studies have been conducted to
      determine the effects of prolonged exposure to non-ionizing, low to moderate
      intensity nanopulses on the growth of pre-neoplastic CL-S1 mammary epithelial
      cells in vitro. Cells were grown in culture and maintained in serum-free defined
      medium containing 10 ng/ml EGF and 10 microg/ml insulin as comitogens. Studies
      showed that 0.25-3.0 h exposure to nanopulses of 18 kV/m field intensity, 1 kHz
      repetition rate and 10 ns pulse width had no effect on CL-S1 cell growth or
      viability during the subsequent 72-h culture period. However, exposure to similar
      nanopulses for prolonged periods of time (4-6 h) resulted in a significant
      increase in cell proliferation, as compared to untreated controls. Additional
      studies showed that nanopulse exposure enhanced CL-S1 cell growth when cells were
      maintained in media containing only EGF, but had no effect on cells maintained in
      defined media that were mitogen-free or containing only insulin. Studies also
      showed that the growth-promoting effects of nanopulse exposure were associated
      with a relatively large increase in intracellular levels of phospho-MEK1 (active)
      and phospho-ERK1/2 (active) in these cells. These findings demonstrate that
      prolonged exposure to moderate levels of UWB enhanced EGF-dependent mitogenesis,
      and that this growth-promoting effect appears to be mediated by enhanced
      activation of the mitogen-activated protein kinase (MAPK) signalling pathway in
      pre-neoplastic CL-S1 mammary epithelial cells.

PMID- 15985062
TI  - Infants' symbolic comprehension of actions modeled with toy replicas.
AB  - While very young children's understanding of objects as symbols for other
      entities has been the focus of much investigation, very little is known
      concerning the emergence of comprehension for symbolic relations among actions
      modeled with toy replicas and their real counterparts. We used videotaped
      depictions of real actions in a preferential looking task to assess toddlers'
      ability to comprehend such connections for action categories aligned with
      familiar object concepts. Across two experiments, 16- and 18-month-olds provided
      no evidence of understanding such relations, even when action categories were
      highlighted with verbal prompts. Among 24- and 26-month-olds, comprehension of
      relations between certain actions modeled with toys and videos of their real
      world counterparts began to emerge, independent of expressive vocabulary size.
      Implications of our results for theoretical conclusions drawn from use of the
      generalized imitation procedure to study early conceptual development are
      discussed.

PMID- 15985063
TI  - A confusion between understanding and understanding symbols.

PMID- 15985065
TI  - Evidence for an age-independent process in category learning.
AB  - After learning to categorize a set of alien-like stimuli in the context of a
      story, a group of 5-year-old children and adults judged pairs of stimuli from
      different categories to be less similar than did groups not learning the category
      distinction. In a same-different task, the learning group made more errors on
      pairs of non-identical stimuli from the same category than did the other groups,
      suggesting increased within-category item similarity, or compression. These
      expansion and compression effects add further support to the view that concept
      formation involves systematic changes in the metric of similarity space within
      which objects are represented. They also suggest that these processes do not vary
      with age, which is at least consistent with the hypothesis that they are
      fundamental to the mechanisms underlying concept formation.

PMID- 15985066
TI  - Very young children are insensitive to picture- but not object-orientation.
AB  - In two experiments on very young children's response to the orientation of
      pictures and objects, 18-, 24- and 30-month-old children showed no preference for
      upright pictures over inverted ones. More importantly, we found that children in
      all three age groups were equally accurate and equally fast at identifying
      depicted objects regardless of orientation. These studies further established
      that young children's insensitivity to picture orientation does not extend to
      objects. These results, in combination with the earlier ones, indicate that only
      gradually do young children come to share the picture orientation preference of
      adults and older children and that their adoption of the orientation convention
      is not based on changes in their ability to process upright and inverted images.

PMID- 15985067
TI  - Sensitivity to triadic attention in early infancy.
AB  - In Study 1, 54 3-, 6- and 9-month-old infants interacted with an adult stranger
      who engaged in a face-to-face (dyadic) exchange. Dyadic interaction was halted
      when the adult turned away to look at an object. In a Joint Attention condition,
      the adult alternated visual attention between the infant and the object, and in a
      Look Away condition she looked away at the object only. Infants gazed and smiled
      more in the Joint Attention condition compared to in the Look Away condition.
      Infants' gazing to the target object interacted with age and condition. In Study
      2, 37 3-, 6- and 9-month old infants interacted with an adult who coordinated
      visual attention and affect, affect only, visual attention only, or ignored the
      infant. Infants gazed reliably more at E when she coordinated both affect and
      attention and smiled reliably more when the adult coordinated affect and
      attention or attention only. The findings show a sensitivity to triadic attention
      by 3 months of age.

PMID- 15985068
TI  - Embedded figures detection in autism and typical development: preliminary
      evidence of a double dissociation in relationships with visual search.
AB  - Individuals with autism show relatively strong performance on tasks that require
      them to identify the constituent parts of a visual stimulus. This is assumed to
      be the result of a bias towards processing the local elements in a display that
      follows from a weakened ability to integrate information at the global level. The
      results of the current study showed that, among children with autism, ability to
      locate a figure embedded in a larger stimulus was only related to performance on
      visual search trials where the target was identified by a unique perceptual
      feature. In contrast, control children's embedded figures performance was
      specifically related to their performance on visual search trials where the
      target was defined by a conjunction of features. This double dissociation
      suggests that enhanced performance on perceptual tasks by children with autism is
      not simply a consequence of a quantitative difference in ability to engage in
      global processing.

PMID- 15985069
TI  - Maternal gestures with 20-month-old infants in two contexts.
AB  - Speech directed towards young children ("motherese") is subject to consistent
      systematic modifications. Recent research suggests that gesture directed towards
      young children is similarly modified (gesturese). It has been suggested that
      gesturese supports speech, therefore scaffolding communicative development (the
      facilitative interactional theory). Alternatively, maternal gestural modification
      may be a consequence of the semantic simplicity of interaction with infants (the
      interactional artefact theory). The gesture patterns of 12 English mothers were
      observed with their 20-month-old infants while engaged in two tasks, free play
      and a counting task, designed to differentially tap into scaffolding. Gestures
      accounted for 29% of total maternal communicative behaviour. English mothers
      employed mainly concrete deictic gestures (e.g. pointing) that supported speech
      by disambiguating and emphasizing the verbal utterance. Maternal gesture rate and
      informational gesture-speech relationship were consistent across tasks,
      supporting the interactional artefact theory. This distinctive pattern of gesture
      use for the English mothers was similar to that reported for American and Italian
      mothers, providing support for universality. Child-directed gestures are not
      redundant in relation to child-directed speech but rather both are used by
      mothers to support their communicative acts with infants.

PMID- 15985070
TI  - Factors responsible for performance on the day-night task: response set or
      semantics?
AB  - In a recent study Diamond, Kirkham and Amso (2002) obtained evidence consistent
      with the claim that the day-night task requires inhibition because the picture
      and its corresponding conflicting response are semantically related. In their
      study children responded more accurately in a dog-pig condition (see /day
      picture/ say "dog"; see /night picture/ say "pig") than the standard day-night
      condition (see /day picture/ say "night"; see /night picture/ say "day").
      However, there is another effect that may have made the day-night condition
      harder than the dog-pig condition: the response set effect. In the day-night
      condition the names of the two stimuli ("day" and "night") and the two
      corresponding conflicting responses ("night" and "day") are from the same
      response set: both "day" and "night". In the dog-pig condition the names of the
      stimuli ("day", "night") and the corresponding responses ("dog", "pig") are from
      a different response set. In two experiments (Experiment 1 with 4-year-olds (n =
      25); Experiment 2 with , 4-, 5-, 7- and 11-year-olds (n = 81)) children were
      tested on four experimental conditions that enabled the effects of semantics and
      response set to be separated. Overall, our data suggest that response set is a
      major factor in creating the inhibitory demands of the day-night task in children
      of all ages. Results are discussed in relation to other inhibitory tasks.

PMID- 15985071
TI  - Motion and color processing in school-age children and adults: an ERP study.
AB  - Stimuli designed to selectively elicit motion or color processing were used in a
      developmental event-related potential study with adults and children aged 6, 7
      and 8. A positivity at posterior site INZ (P-INZ) was greater to motion stimuli
      only in adults. The P1 and N1 were larger to color stimuli in both adults and
      children, but earlier to motion stimuli only in adults. Finally, the P2 was
      larger to color stimuli in adults but larger to motion stimuli in children, and
      earlier to motion stimuli only in children. The findings across components
      indicate development from middle childhood to adulthood in aspects of both the
      motion and color processing systems indexed by this paradigm, but are consistent
      with an hypothesis of a more protracted time course of development for the motion
      as compared to the color processing system.

PMID- 15985072
TI  - Impact of anatomical pielocaliceal topography in the treatment of renal lower
      calyces stones with extracorporeal shock wave lithotripsy.
AB  - AIM: There is wide consensus that the lowest success rate of extracorporeal shock
      wave lithotripsy (ESWL) is in the complete clearance of renal stones located in
      the lower calyces. We assess the effectiveness of extracorporeal shock wave
      lithotripsy monotherapy for lower pole renal calculi to determine the
      relationship between the spatial anatomy of lower pole and the outcome of ESWL.
      METHODS: We evaluated 107 patients who were treated for solitary lower pole renal
      stones less than 20 mm in diameter with ESWL. The spatial anatomy of the lower
      pole, as defined by the lower infundibulopelvic angle, infundibular length and
      infundibular width, was measured by preoperative intravenous pyelography, while
      the stone location and size were determined by using abdominal plain X-ray. All
      patients were followed up at 1 and 3 months with abdominal plain X-ray and
      ultrasonography. RESULTS: Only 62 patients (58%) became stone free, while 45
      (42%) retained residual fragments. A small lower infundibulopelvic angle, a long
      infundibular length and a tight infundibular width are unfavorable for stone
      clearance after ESWL. CONCLUSIONS: ESWL is the treatment of choice for most renal
      and ureteral stones. However, stone clearance from the lower pole following ESWL
      is poor and significantly affected by the inferior pole collecting system
      anatomy. Therefore, we believe it is important to evaluate these anatomical
      factors when deciding on the best treatment for lower pole renal calculi.

PMID- 15985073
TI  - Oxalate-degrading Providencia rettgeri isolated from human stools.
AB  - BACKGROUND: Oxalate-degrading bacteria are thought to metabolize intestinal
      oxalate and thus decrease the urinary excretion of oxalate by reducing its
      intestinal absorption. METHODS: We have isolated several novel oxalate-degrading
      bacteria from human stools. Oxalate degrading bacteria were investigated to
      characterize their protein profiles with antibodies against oxalyl-coenzyme A
      decarboxylase (65 kDa) and formyl-coenzyme A transferase (48 kDa) purified from
      Oxalobacter formigenes. RESULTS: One of these isolates was identified as
      Providencia rettgeri, which showed two proteins (65 kDa and 48 kDa) on sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) that were not found
      in non-oxalate-degrading P. rettgeri. Antibodies reacted with the 65 and 48 kDa
      proteins from the P. rettgeri strain on Western blotting. An Oxalobacter
      formigenes formyl-coenzyme A transferase gene probe reacted with chromosomal DNA
      from P. rettgeri on Southern blotting under high stringency conditions, while an
      Oxalobacter formigenes oxalyl-coenzyme A decarboxylase gene probe did not react
      under the same conditions. CONCLUSIONS: The mechamism of oxalate degradation by
      P. rettgeri appears to be similar to that of Oxalobacter formigenes. This is the
      first report of a facultative oxalate-degrading organism that is one of the
      Enterobacteriaceae.

PMID- 15985074
TI  - Modified pluck method in en bloc nephroureterectomy with bladder cuff for upper
      urothelial cancer.
AB  - AIM: To evaluate the surgical results of the en bloc removal of the kidney and
      ureter with a bladder cuff by using our modified pluck method. METHODS: We
      employed this procedure in 28 patients with renal pelvic and ureteral cancer. The
      clinical stages of the 28 patients were T(1-3)N(0-1)M(0). These patients were
      operated on by nephrectomy with standard open or retroperitoneoscopic surgery,
      and then standard or blind dissection of the distal ureter. After simultaneously
      making a transurethral circular incision of the ureteral meatus with a J-shaped
      electrode, the ureteral end was plucked out of the bladder, and en bloc removal
      of the kidney and ureter was performed from the wound. RESULTS: The mean
      operating time for nephroureterectomy using the pluck method was 278 min in all
      cases. The mean time for the pluck procedure after nephrectomy was 24 min in 22
      cases, and 73 min in six cases where the nephrectomy was carried out via a new
      lower pararectal wound. There were no intra- or postoperative complications
      associated with these procedures. Within the mean follow-up period of 25 months,
      there was no recurrence of tumors in the perivesical retroperitoneal space;
      however, the usual rate of intravesical recurrence was observed. Three patients
      died, two of metastatic urothelial cancer and one of heart disease. CONCLUSIONS:
      En bloc nephroureterectomy using our modified pluck method is a useful procedure
      for patients with upper urothelial cancer because of the simplicity and ease of
      the procedure.

PMID- 15985075
TI  - A comparison of holmium:YAG laser with Lithoclast lithotripsy in ureteral calculi
      fragmentation.
AB  - PURPOSE: Among various intracorporeal lithotriptors, Lithoclast (EMS,
      Switzerland) has become the widely used tool for the treatment of urinary stones.
      Recently, the holmium:YAG laser has been used with a wide range of potential
      urological applications, including intracorporeal lithotripsy of urinary calculi.
      The purpose of the present study is to compare Lithoclast with holmium:YAG laser
      lithotripsy in ureteral calculi fragmentation. METHODS: Out of 51 patients with
      ureteral calculi, 26 underwent Lithoclast lithotripsy and 25 holmium:YAG
      lithotripsy using a 8/9.8F rigid ureteroscope. There were no changes to the
      ureteroscopes, video monitors, baskets or irrigation devices during the study
      period. RESULTS: There were no differences in patient age, sex, stone size and
      location of stones between these groups. The immediate stone-free rates were
      96.0% in the holmium:YAG group and 73.1% in the Lithoclast group (P < 0.05). The
      3-month stone-free rates were 96.0% and 84.6%, respectively (P = 0.350). The mean
      operation time and mean period of postoperative hospitalization in the
      holmium:YAG group (49.8 min and 1.0 days, respectively) were shorter than those
      of the Lithoclast counterpart (76.9 min and 2.5 days, respectively). Post
      treatment complications, such as ureteral perforation, were encountered in only
      two patients who underwent Lithoclast. CONCLUSIONS: Holmium:YAG lithotripsy was
      associated with shorter operation time and postoperative hospitalization period.
      These data also suggest that holmium:YAG lithotripsy was safe and more effective
      than Lithoclast lithotripsy in the aspect of immediate stone free rate. We
      believe that holmium:YAG laser is an excellent treatment modality for managing
      ureteral calculi.

PMID- 15985076
TI  - Systemic chemotherapy in patients with indwelling ureteral stenting.
AB  - BACKGROUND: We investigated whether systemic chemotherapy increased episodes of
      acute pyelonephritis (APN) in patients with an indwelling double-J stent due to
      non-urological malignant ureteral obstruction. METHODS: A retrospective study was
      performed on a total of 74 patients (16 men and 58 women; median age, 53.0;
      range, 34-84 years) with non-urological malignant ureteral obstruction, who were
      managed by double-J stenting between October 1997 and December 2001. The patients
      were divided into those who received (33 patients, group I) and those who did not
      receive systemic chemotherapy (41 patients, group II) during the stent indwelling
      period (median, 7.0; range, 1-44 month). Routine antibiotic prophylaxis was not
      administered to any patient. Median follow-up was 10.5 (range, 1-45) months.
      Clinical features, including the incidence of febrility and APN, were compared
      between the two groups. RESULTS: Of the 74 patients, 18 patients (24.3%)
      experienced acute febrile episodes during ureteral stenting, but only five (6.8%)
      patients were diagnosed as having APN. No significant difference in the incidence
      of fever or APN was found between the two groups (P = 1.000 and P = 0.651,
      respectively). Univariate logistic analysis indicated that only the duration of
      follow-up was a risk factor for an episode of fever. Other parameters had no
      clinical significance. CONCLUSION: Our findings suggest that systemic
      chemotherapy may not predispose the risk of acute pyelonephritis in patients with
      an indwelling ureteral stent due to non-urological malignant ureteral
      obstruction.

PMID- 15985077
TI  - Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and
      its treatment with sildenafil.
AB  - BACKGROUND: We retrospectively evaluated the erectile function after nerve
      sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for
      erectile dysfunction (ED) following RRP according to the preoperative erectile
      function. METHODS: We evaluated 48 Japanese patients who underwent nerve-sparing
      RRP at the Sapporo Medical University School of Medicine, Sapporo, Japan, between
      January 1996 and December 2001. Erectile function following nerve-sparing RRP was
      assessed by a simple mailed questionnaire that was constructed for the study.
      RESULTS: Of the 48 patients, 36 had normal erectile function preoperatively, but
      for 12, function was not sufficient to penetrate. The overall estimated recovery
      rates of any degree of erection were 50.6% at 36 months and 94.3% at 60 months.
      However, that of erection sufficient to penetrate was only 17.7% at 36 months and
      was only seen in bilateral nerve-sparing patients. Sildenafil was effective in 9
      of 13 ED patients (69.2%) in both nerve-sparing groups. When patients were
      divided according to preoperative erectile function, no difference was found in
      the efficacy rate between patients with normal function and those with ED.
      CONCLUSIONS: Even bilateral nerve-sparing RRP can not always guarantee a
      sufficient erection. However, sildenafil is effective for ED following nerve
      sparing RRP regardless of the nerve-sparing procedure or preoperative erectile
      function. Thus, preoperative function alone, although depending on its severity,
      may not necessarily be a reason for exclusion from receiving nerve-sparing RRP if
      patients want to have the operation.

PMID- 15985078
TI  - Ten cases of congenital urethral stricture in childhood with enuresis.
AB  - BACKGROUND: To report short-term clinical outcomes of endoscopic correction of
      congenital urethral stricture in 10 boys who suffer from enuresis resistant to
      conservative therapy. METHODS: Fifteen boys ranging between 5 and 15 years old
      consulted our clinics for nocturnal and diurnal enuresis which had not been
      improved by medication and behavioral therapy. Among them, voiding cystography
      revealed bulbar narrowing (Cobb's Collar) in 10 cases and vesico-ureteral reflux
      was found in four cases (seven ureters). Endoscopically, this lesion was
      recognized as a ring-form stenosis just distal to the urethral sphincter. It was
      incised with infantile urethrotome. RESULTS: Vesico-ureteral reflux was resolved
      in four ureters and improved in one. In all cases, daytime enuresis resolved
      dramatically and night enuresis became controllable. CONCLUSIONS: Boys who suffer
      from diurnal enuresis should immediately be explored for the existence of
      congenital urethral stenosis. Early resolution may bring about better urinary
      behavior.

PMID- 15985079
TI  - Bcl-2 protein and DNA ploidy in renal cell carcinoma: do they affect patient
      prognosis?
AB  - AIM: The aim of the present study was to correlate bcl-2 protein expression and
      DNA-ploidy status with established prognostic parameters in renal cell carcinoma
      (RCC) and to examine their impact on disease progression and patient survival.
      METHODS: Both parameters were prospectively measured in 50 consecutive radical
      nephrectomy specimens using flow cytometry. They were correlated with the tumor
      grade, stage and histological type. Kaplan-Meier survival analysis for all
      parameters was performed. RESULTS: Bcl-2 protein expression was higher in RCC
      compared to normal renal tissue (P < 0.0001). Aneuploid tumors had higher bcl-2
      expression compared to diploid tumors (P = 0.015). Bcl-2 expression and DNA
      content were not correlated with tumor histological types (P = 0.277/P = 0.419),
      grades (P = 0.690/P = 0.449), T categories (P = 0.637/P = 0.585) or stages (P =
      0.726/P = 0.800). Median follow-up time was 46 months (range, 5-84) with a mean
      overall survival of 61.8 months (95% confidence interval, 53.7-69.9). Tumor stage
      was the only statistically important prognostic factor (P = 0.0045). CONCLUSION:
      Although Bcl-2 expression was correlated with tumor DNA content, the prognostic
      value of these two parameters following radical nephrectomy was not established.

PMID- 15985080
TI  - Effects of platelet-activating factor on nitrergic transmission in rabbit corpus
      cavernosum.
AB  - AIM: The information currently available suggests that nonadrenergic
      noncholinergic (NANC) transmitters, particularly nitric oxide, are involved in
      the relaxation of penile erectile tissues. Platelet-activating factor (PAF) is a
      chemical mediator and is involved in many physiological and pathophysiological
      events. It is well known that several of the vascular actions of PAF are mediated
      by the generation of nitric oxide. We designed this study to test the hypothesis
      that PAF has an effect on NANC responses in rabbit corpus cavernosum strips.
      METHODS: Rabbit corpus cavernosum strips were precontracted with phenylephrine
      (10(-5) mol/L). Isometric tension changes produced by carbachol (10(-9)-10(-5)
      mol/L), sodium nitroprusside (10(-8)-10(-5) mol/L) and electrical field
      stimulation (for 10 s at sequential frequencies of 2, 4, 8, 16, and 32 Hz as
      square-wave pulses of 50 mV) were recorded with a pressure transducer. These
      relaxations were compared to those obtained in the presence of PAF. RESULTS: PAF
      had no effect on endothelium-dependent, endothelium-independent or electrical
      field stimulation-induced NANC relaxation responses in isolated rabbit corpus
      cavernosum strips. There was no statistically significant difference between the
      pD(2) and E(max) values for carbachol or sodium nitroprusside in the presence of
      PAF. CONCLUSIONS: Our results suggest that PAF does not modify the endothelium
      dependent, endothelium-independent or electrical field stimulation-induced NANC
      relaxation responses in isolated rabbit corpus cavernosum strips.

PMID- 15985081
TI  - Delayed adrenal insufficiency long after unilateral adrenalectomy: prolonged
      glucocorticoid therapy reduced reserved secretory capacity of cortisol.
AB  - A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy
      for left adrenal adenoma. After 7 years of prednisolone treatment (with some
      interruptions), followed by 4 years of total withdrawal from prednisolone
      treatment, she presented with hypotension, weight loss, general fatigue, nausea,
      hyponatremia and hypoglycemia. These clinical features together with a low
      response in the rapid adrenocorticotropic hormone test led to the diagnosis of
      acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone
      levels in the face of increased demand for cortisol during adrenal crisis
      suggested a disordered hypothalamic-pituitary function, indicating secondary
      adrenal insufficiency. This patient demonstrated the etiology of acute adrenal
      insufficiency long after unilateral adrenalectomy in association with subsequent
      glucocorticoid therapy. A reduction in the reserved secretory capacity of
      cortisol after prolonged prednisolone treatment was considered to have induced
      secondary adrenal insufficiency, even after 4 years of total withdrawal from
      prednisolone.

PMID- 15985082
TI  - Distal ureteral atresia: recovery of renal function after relief of obstruction
      at ten months old.
AB  - A large cystic mass that occupied more than half of the abdomen was identified by
      ultrasound in a 10-month-old boy. Intravenous pyelography failed to visualize the
      right kidney, so we created a loop ureterocutaneostomy followed by temporary
      nephrostomy to improve renal function. Exploratory surgery revealed complete
      atresia of the distal right ureter. A ureteral stricture developed after
      ureteroneocystostomy and undiversion of the loop, so a second reconstruction
      procedure was required (pelvi-ureteroplasty and reimplantation of the right
      ureter with a psoas hitch) to free the patient from dependence on catheters.
      Despite the occurrence of giant hydronephrosis secondary to complete ureteral
      obstruction at the age of 10 months, the function of the right kidney could be
      preserved. Accordingly, aggressive attempts to promote functional recovery may be
      justified even when patients have advanced hydronephrosis.

PMID- 15985083
TI  - Bladder-sparing surgery and continent urinary diversion using the appendix
      (Mitrofanoff procedure) for urethral cancer.
AB  - We performed bladder-sparing surgery and continent urinary diversion in two
      patients with urethral cancer. The first patient was a 58-year-old man with
      bulbomembranous urethral cancer (squamous cell carcinoma, cT2N0M0). The second
      patient was a 77-year-old woman with urethral cancer invading the vaginal wall
      (transitional cell carcinoma with squamous cell carcinoma, cT3N0M0). After
      bladder-sparing urethrectomy, continent urinary diversion with
      appendicovesicostomy (Mitrofanoff procedure) was performed in the both patients.
      More than 4 years after the surgery, both patients were continent, had no trouble
      with catheterization, and experienced no recurrence of cancer. Bladder-sparing
      surgery and urinary diversion based on the Mitrofanoff procedure can be
      considered for appropriately selected patients with urethral cancer.

PMID- 15985084
TI  - Varicocele rupture due to sexual intercourse.
AB  - Varicocele rupture was diagnosed in a 23-year-old man who presented with swelling
      and pain in the left scrotum after sexual intercourse. Color Doppler
      ultrasonography revealed blood flowing into the space surrounding the left
      testis, a hematoma and reflux of blood in the left spermatic vein. Varicocele
      rupture is a very rare condition and there have been only five reported cases.

PMID- 15985085
TI  - Different transformation of mature teratoma in a patient with mixed germ cell
      tumor of the testis.
AB  - A 44-year-old male was referred with a left supraclavicular lymphadenopathy. A
      biopsy of the lymph node showed metastatic embryonal carcinoma. Tumor markers
      were present at high levels: alpha-fetoprotein 253.9 ng/mL, beta-human chorionic
      gonadotrophin 62 ng/mL. Computed tomography (CT) showed retroperitoneal
      adenopathy. High orchiectomy was done. The patient was treated with three cycles
      of etoposide plus cisplatin, achieved normalization of the serum tumor markers
      and underwent retroperitoneal lymph node dissection. Pathological findings of
      multiple lymph nodes showed teratomatous glands without viable cells. At follow
      ups performed every 3 months, tumor markers remained within normal limits and no
      evidence of recurrence was observed. Eight years after first admission a CT scan
      revealed a cystic tumor 1 cm in diameter in the para-aortic region. The cystic
      tumor continued to slowly grow, expanding by 1 cm in diameter per year without
      elevation of tumor markers. The para-aortic tumor had grown to 4 cm in diameter
      and a left supraclavicular lymphadennopathy recurred. A resection of the
      supraclavicular cystic tumor showed mucinous cystadenocarcinoma, but a cystic
      tumor in the para-aortic region revealed mature teratoma. Here we report a case
      of mature teratoma with metastases at supraclavicular and para-aortic lymph nodes
      which had different transformations in spite of both regions consisting of cystic
      tumors.

PMID- 15985086
TI  - Splenogonadal fusion: report of a case.
AB  - A 15-year-old male patient was admitted to our hospital with a left undescended
      testis. He also suffered from congenital limb defects. Ultrasonography revealed
      atrophic testicular tissue in the left groin, approximately 2-cm in size. Upon
      left inguinal exploration, atrophic testicular tissue was found and an
      orchidectomy was performed. Histopathological examination revealed splenogonadal
      fusion, which has a known association with congenital limb defects.

PMID- 15985087
TI  - Successful cure of dermatomyositis after treatment of nonseminomatous testicular
      cancer.
AB  - Although the association between dermatomyositis and cancer is well recognized,
      there have been a limited number of reports of dermatomyositis associated with
      testicular cancer. We report the case of a 31-year-old man who was diagnosed with
      dermatomyositis. Because the patient's serum levels of alpha-fetoprotein and
      human chorionic gonadotropin beta subunit were elevated, the patient was referred
      to our department. Physical examination revealed an induration (2 cm x 2 cm) in
      the left testis and the patient was diagnosed with stage IIIB left testicular
      cancer. A left high orchidectomy was then performed, and pathological examination
      revealed embryonal carcinoma. The patient was started on a systemic
      chemotherapeutic (etoposide, ifosfamide and cisplatin; VIP) regimen. After the
      third chemotherapy session, metastases had completely disappeared, the serum
      levels of alpha-fetoprotein and human chorionic gonadotropin beta subunit had
      normalized and the dermatomyositis symptoms had improved. Cancer is known to be a
      trigger of dermatomyositis. This case illustrates the importance of palpation of
      the testes in young patients with dermatomyositis.

PMID- 15985088
TI  - Primary testicular leiomyosarcoma.
AB  - We report a case of primary testicular leiomyosarcoma. A 76-year-old man, who
      complained of left scrotal swelling for 6 months, underwent radical orchiectomy.
      Microscopic examination revealed intratesticular leiomyosarcoma. The patient
      received no adjuvant therapy and at 12 months after surgery, there had been no
      recurrence. Primary leiomyosarcoma of the testis is extremely rare; this is the
      9th case recorded worldwide.

PMID- 15985089
TI  - Sigmoidorectal (Mainz II) pouch for continent urinary diversion in bladder
      cancer.
AB  - BACKGROUND: We aimed to assess the feasibility, safety, and outcome of the
      sigmoidorectal (Mainz II) pouch for urinary diversion in patients with invasive
      bladder cancer. METHODS: Twenty-nine patients (25 men and four women), aged 65-76
      years, who had undergone radical cystectomy and the sigmoidorectal pouch
      procedure for invasive bladder cancer were included in this study. Postoperative
      evaluations included metabolic testing, standard laboratory screening, renal
      ultrasonography, pouchography, and intravenous urography or pouchoscopy when
      indicated. RESULTS: The median operative time was 175 min. Urine leakage was
      encountered in two patients (6.8%), deep vein thrombosis in one (3.4%), and ileus
      necessitating surgery in another one. Two patients developed pyelonephritis due
      to ureterocolonic stricture, which was treated with antegrade balloon dilatation.
      No local relapses of bladder cancer were found. All patients were continent
      during the day, but one patient was occasionally incontinent during the night. In
      the long term, six patients (20.6%) developed metastatic disease, and five
      patients (17.2%) died because of cancer-related causes. Overall survival was 100,
      96 and 60% at 1, 2 and 3 years after the operation, respectively. The mean
      survival was 36.8 +/- 1.9 months, which was statistically significantly
      associated with the M stage (P < 0.001), but not with the T (P = 0.091) or N (P =
      0.081) stages. CONCLUSIONS: The sigmoidorectal (Mainz II) pouch seems to be a
      feasible, safe and effective method for continent urinary diversion. It is able
      to provide good quality of life, and ensure good overall survival rates.

PMID- 15985090
TI  - Modified endoscopic live donor nephrectomy: retroperitoneoscopy followed by hand
      assistance.
AB  - We have developed a novel modification of previous approaches to donor
      nephrectomy and herein review our original operative procedure. First, the
      posterior aspect of the kidney was dissected retroperitoneoscopically and
      dissection of the renal artery, ureter and gonadal vein was almost completed.
      Second, the anterior aspect of the kidney was dissected with transperitoneal hand
      assistance, and dissection of the renal pedicle from the anterior surface was
      accomplished easily and safely. This operative procedure was successfully
      performed for two donors with no intraoperative or postoperative complications.
      Our modified endoscopic donor nephrectomy is feasible as a minimally invasive
      procedure because of its safety, and its ability to preserve renal function and
      establish an excellent operative field for both posterior and anterior aspects of
      the kidney.

PMID- 15985091
TI  - Minimizing errors in health care: focusing on the "root cause" rather than on the
      individual.

PMID- 15985093
TI  - An exploratory study of nurses suffering from severe acute respiratory syndrome
      (SARS).
AB  - In 2003, severe acute respiratory syndrome (SARS) came to be recognized as a
      newly emergent form of disease that is highly contagious. The aim of this study
      was to describe the perceptions of nurses with SARS in Hong Kong, as the
      perceptions of nurses who have suffered from SARS have not been studied. Ten
      nurses who had suffered from SARS were interviewed, either face-to-face or by
      telephone, about their subjective experiences. These interviews provided in
      depth, descriptive data, which were analysed using content analysis. Nine broad
      categories were identified: uncertainty, information control, feelings of anger
      and guilt, lack of preparation and fear of death, feelings of isolation and
      loneliness, physical effects, support, change of perspective of life, and change
      of perspective of nursing. Although the dreaded disease affected the nurses
      tremendously, both physically and psychologically, it has also had its positive
      side. As a result of experiencing the illness, the participants came to treasure
      relationships, health and everyday life more. In caring for patients, they came
      to see the world more from the perspective of the patients. They found that they
      need to take the time to reassure patients and families and to seriously listen
      to all of their concerns.

PMID- 15985092
TI  - Exploring the relationship between nursing protocols and nursing practice in an
      Irish intensive care unit.
AB  - Nursing practice no longer relies on tradition or ritual; instead, it is based on
      research and empirical evidence. The emphasis on evidence-based nursing, as well
      as standardization of nursing practice, has resulted in the production of
      policies, protocols and guidelines aimed at directing numerous aspects of nursing
      care. The aim of this study was to explore the relationship between these
      documents and actual nursing practice. To this end, this descriptive study
      employed a case study approach to examine the experiences of nurses in an Irish
      intensive care unit with a protocol on endotracheal tube suctioning. Focus group
      interviews of 17 nurses in six focus groups provided a significant insight into
      the experiences of these nurses in relation to policies, protocols and
      guidelines. Analysis of the data afforded some highly relevant findings,
      including the fact that nurses adapt clinical protocols as they see fit, thus
      demonstrating the importance that they place on their own professional judgement
      and autonomy.

PMID- 15985094
TI  - The relationship between patient blood pathology values and patient falls in an
      acute-care setting: a retrospective analysis.
AB  - Few studies have investigated the relationship between patient falls and patient
      blood pathology values, which can reveal objective information about the health
      and nutritional status of a patient. It could be that some abnormal values are
      associated with patients that fall. The objectives of the current study were to
      determine whether blood pathology values were different in patients who fell
      compared to patients who did not fall, and whether there was a difference in the
      type and number of currently documented risk factors for falls found for patients
      who fell compared to patients who did not fall. A retrospective audit of patient
      incident reports and medical records was conducted in an acute-care hospital for
      220 patients who fell and who did not fall. Faller and non-faller patients were
      matched by casemix type and length of stay. Findings revealed a significant
      relationship between patients who fell and the variables of age, confusion status
      and alkaline phosphatase blood values.

PMID- 15985095
TI  - Improved healing rates for chronic venous leg ulcers: pilot study results from a
      randomized controlled trial of a community nursing intervention.
AB  - Venous leg ulcers are a frequent source of chronic ill-health and a considerable
      cost to health-care systems. This paper reports pilot study results from a
      randomized controlled trial to determine the effectiveness of a community-based
      'Leg Club' environment on improving healing rates of venous leg ulcers. Leg Clubs
      offer a setting where people with similar problems can socialize in a supportive,
      information-sharing environment. A sample of 33 clients with a below-knee venous
      leg ulcer were randomized to treatment, either in their own homes or in a
      community Leg Club. Treatment was provided to all participants, whether in the
      control group or intervention group, by a team of trained wound-care nurses
      following evidence-based assessment and treatment guidelines. Data were collected
      on admission to the study and at 12 weeks from admission. Results showed a
      significant improvement in healing in the intervention group compared to the
      control group, as measured by ulcer area size and Pressure Ulcer Scale for
      Healing scores. These results suggest that a community Leg Club environment
      provides benefits additional to wound care expertise and evidence-based care.
      Knowledge gained from this study provides evidence to guide service delivery and
      improve client outcomes.

PMID- 15985096
TI  - Validation of the Australian/English version of the Diabetes Management Self
      Efficacy Scale.
AB  - Australians' use of the English language is influenced by a British educational
      curriculum, exposure to international television programmes and cultural
      backgrounds. Hence, adapting research instruments for use with Australian
      populations can be challenging. This study adapted the United Kingdom's version
      of the 20-item Diabetes Management Self-Efficacy Scale and tested it
      psychometrically with Australians. Face validity of the adapted instrument was
      established through consultation with diabetes educators and people with type 2
      diabetes. Data from a convenience sample of 88 people with type 2 diabetes were
      analysed to determine the psychometric properties of the adapted instrument. The
      results indicate that the Australian/English version of the instrument is
      internally consistent, stable over time and it measures self-efficacy. However,
      there was evidence to show that there might be some redundant items in the scale.
      Further psychometric testing is warranted with a larger sample to determine
      whether the scale requires refinement.

PMID- 15985097
TI  - Reaching for the stars: career advancement and the registered nurse.
AB  - Clinical nursing has long struggled to secure the place of primacy it deserves in
      the profession's hierarchy of importance and worth. It is ironic that, even at
      the beginning of the 21st century, a clinical nurse is generally not as well
      recognized, rewarded or remunerated as a colleague working in nursing management,
      education or research. Until the profession recognizes and takes serious action
      to remedy this situation, the crisis of recruitment and retention in nursing
      currently ravaging the globe is likely to continue. In this paper, I present a
      discursive account of an exciting initiative by a leading private, acute-care
      hospital which addresses this very problem. A new ladder for clinical nurse
      specialists (CNSs) introduces a rigorous and systematic approach to the
      appointment of three classifications of CNS, each requiring evidence of
      successively higher levels of competency, and which are accompanied by fiscal
      reward and stronger peer recognition.

PMID- 15985101
TI  - Terminating migraine with allodynia and ongoing central sensitization using
      parenteral administration of COX1/COX2 inhibitors.
AB  - OBJECTIVE: To determine whether delayed infusion of COX1/COX2 inhibitors
      (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress
      ongoing sensitization in central trigeminovascular neurons in the rat.
      BACKGROUND: The majority of migraineurs seeking secondary or tertiary medical
      care develop cutaneous allodynia during the course of migraine, a sensory
      abnormality mediated by sensitization of central trigeminovascular neurons in the
      spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain
      free within a narrow window of time (20 to 120 minutes) that opens with the onset
      of pain and closes with the establishment of central sensitization. Can drugs
      that tackle ongoing central sensitization render allodynic migraineurs pain free
      after the window for triptan therapy has expired? METHODS: Patients exhibiting
      migraine with allodynia were divided in two groups (n=14, each): group 1 received
      delayed sumatriptan injection (6 mg) 4 hours after onset of attack--which failed
      to render them pain free-and ketorolac infusion (two 15-mg boluses) 2 hours
      later; group 2 received delayed ketorolac monotherapy 4 hours after onset of
      attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative
      sensory testing) were measured when the patients were migraine free (baseline); 4
      hours after onset of migraine (just before treatment); 2 hours after sumatriptan;
      1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4
      mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral
      and central trigeminovascular neurons. The induction of sensitization (using
      topical application of inflammatory soup on the dura) and its suppression by
      COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity
      and responses to mechanical and thermal stimuli. RESULTS: Patients had normal
      skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4
      hours after onset of migraine. In group 1, all patients continued to exhibit
      allodynia 2 hours after sumatriptan treatment, and none of them became pain free.
      However, 71% and 64% of the patients in groups 1 and 2, respectively, were
      rendered free of pain and allodynia within 60 minutes of ketorolac infusion.
      Nonresponders from both groups, in contrast to the responders, had had a history
      of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked
      sensitization in meningeal nociceptors and suppressed ongoing sensitization in
      spinal trigeminovascular neurons. This inhibitory action was reflected by
      normalization of neuronal firing rate and attenuation of neuronal responsiveness
      to mechanical stimulation of the dura, as well as mechanical and thermal
      stimulation of the skin. CONCLUSIONS: The termination of migraine with ongoing
      allodynia using COX1/COX2 inhibitors is achieved through the suppression of
      central sensitization. Although parenteral administration of COX1/COX2 inhibitors
      is impractical as routine migraine therapy, it should be the rescue therapy of
      choice for patients seeking emergency care for migraine. These patients should
      never be treated with opioids, particularly if they had no prior opioid exposure.

PMID- 15985102
TI  - Teaching headache in America: survey of neurology chairs and residency directors.
AB  - OBJECTIVE: To determine the status of headache education in American medical
      schools and Neurology Residency Training Programs. METHODS: One hundred and
      thirty-three programs were identified using the Association of University
      Professors of Neurology listing. Two hundred and seventeen surveys were mailed to
      departmental chairs (DC) and residency training directors (RTD) with fax back
      response sheets enclosed. Two additional mailings were sent to nonresponders.
      Questions regarding the presence of medical school or resident educational
      opportunities in headache medicine including lectures and electives were
      included. Additional questions were asked to assess beliefs about headache
      education in America. RESULTS: One hundred nineteen surveys were returned. Ninety
      five institutions responded including 75 Chairs and 44 RTD. Eighty percent of
      institutions have formal medical school lectures in headache/migraine. Fifty-five
      institutions claim to have a headache clinic, 52 within neurology departments.
      Thirty-two percent offer a headache elective to medical students. Nearly all
      departments offer formal resident lectures in headache/migraine, and 57% offer a
      headache elective. Essentially, all individual respondents believe that migraine
      is a valid neurological disorder and an important subject to teach in medical
      school. Ninety-one agree or strongly agree that headache is an important public
      health issue. Twenty-nine percent agree or strongly agree that headache diagnosis
      and management is adequately taught. Eighty-four percent believe the
      pharmaceutical industry has influenced migraine education and management. No
      important differences in response were found between Chairs and RTD. CONCLUSIONS:
      This survey provides the first comprehensive assessment of the status of headache
      medicine education in academic departments of neurology.

PMID- 15985103
TI  - Headache in medical education: medical schools, neurology and family practice
      residencies.
AB  - OBJECTIVE: To explore the extent of headache education received by medical
      students and residents. BACKGROUND: Headache is a common, often severe, and
      sometimes disabling problem. However, 49% of sufferers do not seek professional
      treatment-of those who do, only 28% are very satisfied. One possible reason is
      limited education of physicians about headache. METHODS: Surveys were sent to all
      allopathic and osteopathic medical schools, 200 family medicine residencies, and
      all 126 neurology residencies. Information requested included the amount and
      perceived adequacy of headache education and any plans to increase headache
      education. RESULTS: Response rates were 35% to 40%. Medical school lecture hours
      ranged from 0 (4%) to >5 (24%) with 92% having no plans for an increase in
      headache education. Family Medicine residency lecture hours ranged from 1--3
      (30%) to >5 (34%) and case presentations from 1--5 (23%) to >5 (41%), with 88% of
      program directors having no plans for increase. Neurology residency lecture hours
      ranged from 1--3 (11%) to >5 (64%) and case presentations from 1--5 (23%) to>0
      (57%), with 80% having no plans for increase. CONCLUSION: Undergraduate medical
      education in headache is limited. Despite medical schools perceiving their
      training as adequate, both neurology and family practice residency program
      directors believe entering residents are inadequately prepared in headache upon
      entering the program.

PMID- 15985105
TI  - Effects on productivity and quality of life of rizatriptan for acute migraine: a
      workplace study.
AB  - OBJECTIVE: To evaluate the impact of treatment with rizatriptan 10 mg on jobs and
      quality of life of patients with migraine. METHODS: Prospective, open-label study
      at 27 work sites of 20 companies representing diverse labor sectors in Spain.
      Eligible patients according International Headache Society (IHS) criteria were
      recruited for the study by on-site physicians and instructed to treat moderate or
      severe migraine attacks with one tablet of rizatriptan 10 mg. They were asked to
      complete the study questionnaires (ML-96, SF-36) at baseline, and then 3 months
      later. RESULTS: A total of 259 patients (83 men and 176 women) of a mean age of
      39 (range 18 to 61 years) completed the study. Only 7% had taken triptans before
      for treatment of their migraine attacks. After 3 months of rizatriptan therapy,
      the use of medical services was significantly lower and all tested domains of
      quality of life had improved (P<.001). Absenteeism and days worked during
      migraine attacks also fell significantly during 3 months of rizatriptan therapy
      as compared with the 3 months before the study (P<.001). The improvement in
      productivity was reflected in the significant decreases in lost workday
      equivalents (decrease from 3.32 to 1.21 days; P<.001) and also in the total
      number of workdays lost (decrease from 5.16 to 1.82 days; P<.001). Two-thirds of
      patients described the efficacy of oral rizatriptan as excellent or very good
      (62%), and 89% preferred it over their usual medications for acute treatment of
      migraine attacks. CONCLUSION: For this employed population of patients with
      migraine, treatment with rizatriptan significantly improved parameters measuring
      direct medical costs, work and productivity, and health-related quality of life.
      In accordance with these findings, direct and indirect costs related to migraine
      could be substantially reduced by gathering detailed information about the nature
      of headache, eliminating triggering factors, and instituting effective treatment
      of migraine attacks.

PMID- 15985104
TI  - Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double
      blind, randomized trial.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in
      migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor
      response to sumatriptan therapy for acute migraine attacks has been documented in
      the literature, but few controlled trials have investigated the efficacy of an
      alternative triptan in this subgroup of patients. METHODS: Patients with an
      International Headache Society diagnosis of migraine who self-described as
      experiencing at least two unsatisfactory responses to sumatriptan treated their
      first migraine attack with open-label sumatriptan 50 mg. Patients who did not
      achieve 2-hour pain relief (improvement of headache from moderate/severe to
      mild/no headache) were then randomized to treat their second attack with
      almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the
      first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief
      with sumatriptan and were randomized to treatment of their second attack with
      almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated
      their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at
      baseline. Two-hour pain-relief rates were significantly higher with almotriptan
      compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for
      almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005)
      and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack,
      7.1% of patients in the almotriptan group experienced adverse events compared to
      5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an
      effective and well-tolerated alternative for patients who respond poorly to
      sumatriptan 50 mg. A poor response to one triptan does not predict a poor
      response to other agents in that class.

PMID- 15985106
TI  - Characterization and prediction of emergency department use in chronic daily
      headache patients.
AB  - OBJECTIVE: To examine the characteristics of chronic daily headache sufferers who
      use emergency departments (EDs) and identify factors predictive of ED visits.
      BACKGROUND: Several large clinical trials have found that a sizable subset of
      headache patients uses EDs frequently, although such visits should be
      preventable. METHODS: Participants in two large clinical trials provided baseline
      data on ED use, hospitalizations, disability, daily activities, and quality of
      life. RESULTS: Of the 785 patients included, 182 (23.2%) reported at least 1 ED
      visit over the past year. Most of these patients (82.9%) reported one to six
      visits; however, 4.4% reported>/=21 visits (mean 5.0; SD 8.5). The percentage of
      patients with overnight hospitalizations during the previous year was
      significantly greater in the ED user group than non-ED user group (17.6% vs 1.7%;
      P<.001), as was the number of visits to healthcare practitioners (median 24.3 vs
      11.8; P<.001). Compared with non-ED users, a higher percentage of ED users
      reported severe disability on the Migraine Disability Assessment Scale (MIDAS)
      (85.7% vs 69.3%, P<.001) and indicated that their headache more negatively
      impacted mood and daily activities (all P<.05). ED users also had significantly
      higher depression scores and lower scores on all domains of the Short Form--36
      (SF--36) (all P<.05). In a logistic regression model, patient age, neurologist
      visit, severe (vs not severe) rating on the MIDAS, Role Physical (SF--36), and
      prior overnight hospitalization were significant predictors of ED use (max-
      rescaled R(2)=21.0%). CONCLUSIONS: Patients seeking ED treatment for chronic
      daily headache are more severely affected and have more unmet medical needs than
      those who do not use the ED. Management strategies that help prevent frequent ED
      use might be possible.

PMID- 15985107
TI  - Efficacy and tolerability of intravenous valproic acid in acute adolescent
      migraine.
AB  - OBJECTIVE: To describe the efficacy and tolerability of rapid intravenous
      valproic acid (VPA) infusions in children with severe migraine headache.
      BACKGROUND: Intravenous VPA is an emerging treatment option for acute migraine
      headache. Adult data suggests both efficacy and tolerability of rapid VPA
      infusions as abortive therapy, but little data exist in children. METHODS: We
      conducted a retrospective chart review of all children who received intravenous
      VPA at The Children's Hospital Headache Clinic during an 18--month study period.
      Baseline intensity of headache pain, time at which maximum relief was attained,
      pain reduction following therapy, dose and duration of VPA infusion(s), patient's
      pulse, blood pressure, respiratory rate, and pulse oximetry were collected.
      Adverse events were also recorded. RESULTS: Thirty-one children (age=15+/- 2
      years; 81% female) requiring 58 clinic visits and 71 VPA infusions were included.
      Most visits (n=45; 78%) resulted in only one dose of VPA (976+/- 85 mg infused
      over 12+/- 4 minutes) for desired pain relief. Percent pain reduction in those
      children was 39.8%, with time to maximum relief of 63+/- 31 minutes. Some
      children required a second dose of 500 mg (n=13 visits; 22%), that was infused
      over 14+/- 6 minutes and produced a 57% reduction in pain intensity from
      baseline. VPA infusions were well tolerated. Adverse events described included
      cold sensation (1), dizziness (3), nausea (1), possible absence seizure (1),
      paraesthesia (2), and tachycardia (2). CONCLUSIONS: Rapid infusion of intravenous
      VPA is generally well tolerated and may play a role in the management of children
      with acute migraine headache. Prospective, controlled trials to further
      investigate this treatment in children are warranted.

PMID- 15985108
TI  - Headache and sleep: examination of sleep patterns and complaints in a large
      clinical sample of migraineurs.
AB  - OBJECTIVES: This study characterized sleep parameters and complaints in a large
      clinical sample of migraineurs and examined sleep complaints in relation to
      headache frequency and severity. BACKGROUND: The relationship between headache
      and sleep has been documented at least anecdotally in medical literature for well
      over a century and clinical texts allude to the importance of sleep as a headache
      precipitant. A small number of empirical studies have emerged, but the precise
      nature and magnitude of the headache/sleep association and underlying mechanisms
      remain poorly understood. METHODS: In this investigation, 1283 migraineurs were
      drawn from 1480 consecutive headache sufferers presenting for evaluation to a
      tertiary headache clinic. Patients underwent a physical examination and
      structured interview assessing a variety of sleep, headache, and demographic
      variables. Migraine was diagnosed according the IHS criteria (1.1 to 1.6
      diagnostic codes). Migraineurs were 84% female, with a mean age of 37.4 years.
      Groups were formed based on patient's average nocturnal sleep patterns, including
      short, normal, and long sleep groups, and were compared on headache variables.
      RESULTS: Sleep complaints were common and associated with headache in a sizeable
      proportion of patients. Over half of migraineurs reported difficulty initiating
      and maintaining sleep at least occasionally. Many in this sample reported
      chronically shortened sleep patterns similar to that observed in persons with
      insomnia, with 38% of patients sleeping on average 6 hours per night. Migraines
      were triggered by sleep disturbance in 50% of patients. "Awakening headaches" or
      headaches awakening them from sleep were reported by 71% of patients.
      Interestingly, sleep was also a common palliative agent for headache; 85% of
      migraineurs indicated that they chose to sleep or rest because of headache and
      75% were forced to sleep or rest because of headache. Patients with chronic
      migraine reported shorter nightly sleep times than those with episodic migraine,
      and were more likely to exhibit trouble falling asleep, staying asleep, sleep
      triggering headache, and choosing to sleep because of headache. Short sleepers
      (ie, average sleep period 6 hours) exhibited significantly more frequent and more
      severe headaches than individuals who slept longer and were more likely to
      exhibit morning headaches on awakening. CONCLUSIONS: These data support earlier
      research and anecdotal observations of a substantial sleep/migraine relationship,
      and implicate sleep disturbance in specific headache patterns and severity. The
      short sleep group, who routinely slept 6 hours per night, exhibited the more
      severe headache patterns and more sleep-related headache. Sleep complaints
      occurred with greater frequency among chronic than episodic migraineurs. Future
      research may identify possible mediating factors such as primary sleep and mood
      disorders. Prospective studies are needed to determine if normalizing sleep times
      in the short sleeps would impact headache threshold.

PMID- 15985109
TI  - Headache in Behcet's syndrome.
AB  - OBJECTIVE: To study the frequencies and characteristics of different headache
      types seen in patients with Behcet's syndrome (BS) in a large cohort of patients.
      BACKGROUND: Patients with BS may present with different neurological problems,
      related either directly or indirectly to the disease, with headache being the
      most common neurological symptom seen in this syndrome, as well as independent
      from neurologic involvement. METHOD: This study was carried out at the
      multidisciplinary Behcet outpatient clinic of the Behcet's Syndrome Research
      Center. Every fifth admitted patient who had fulfilled the International Study
      Group for Behcet's Disease classification criteria was recruited for this study.
      Each patient was interviewed by one of the examining neurologists through a
      semistructured questionnaire. In case of the presence of more than one headache
      type, the best defined one was diagnosed and evaluated. All patients received a
      complete neurological and physical examination. A chi(2) test was used to
      evaluate the differences between frequencies. One sample t-test was used to
      compare means. The prevalence rates of primary headaches were compared with
      results of the Turkish Headache Epidemiology study by using goodness-of-fit test.
      RESULTS: Two hundred and twenty-eight patients were studied. Headache was
      reported in 66.2% (151/228) of the study cohort. Primary headaches were seen in
      38.6% of the patient population, which corresponds to 58% of BS patients with any
      type of headache. Tension-type headache (TTHA) and migraine were seen in 23.6%
      and 14.9% of the whole study cohort, respectively. In 5.2% of the study cohort,
      the headache was associated with neurological involvement and in 3.9% to uveal
      inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of
      moderate severity was reported in 18.4% of the study cohort who did not fulfill
      the criteria of the International Headache Society (IHS) for any of the primary
      headaches. It was commonly associated with exacerbations of the mucocutaneous
      symptoms of the syndrome. The neurological examination was normal in all of these
      patients. This type of headache was categorized as the nonstructural headache of
      Behcet. CONCLUSION: Headache is the most common neurological symptom seen in BS,
      both in patients with and without neurological involvement. The results of our
      study reveal that headache is seen in a majority of patients with neurological
      involvement due to BS and in a minority with uveal inflammation. The prevalence
      of migraine and TTHA are close to the population in general, but a nonstructural
      migrainous headache, which is commonly associated with exacerbations with some of
      the systemic symptoms of the syndrome, is noteworthy in patients with BS. This
      form of headache is not specific for this disorder, but may be explained by a
      vascular headache triggered by the immunomediated disease activity in susceptible
      individuals.

PMID- 15985110
TI  - Time-series data and the "migraine generator".
AB  - OBJECTIVE: To examine circadian and menstrual patterns of migraine frequency in
      order to identify properties of the putative migraine generator. METHODS:
      Analysis of circadian and menstrual migraine attack frequency distributions,
      using between-interval differences as estimates, at each time point, of the
      derivative of the equation that would, theoretically, model the observed
      oscillating functions. RESULTS: Circadian and menstrual analyses exhibit many
      similarities that are consistent with a single migraine generator in the final
      common pathway for expression of the phenotype. These analyses are inconsistent
      with a role for cortisol or ACTH to be activators of the putative migraine
      generator, could be consistent with visual stimulation as a deactivator of the
      generator, and may also be consistent with a low threshold concentration of
      estradiol and/or progestagens as inactivators of the migraine generator.
      CONCLUSIONS: Analysis of time-series data using differentials uncovers some
      previously unidentified chronobiological properties of migraine, helps select
      amongst various candidate provocative factors, and suggests some properties of a
      putative migraine generator.

PMID- 15985111
TI  - Plasma cytokine levels in migraineurs and controls.
AB  - BACKGROUND: The vasoactive peptide, calcitonin gene-related peptide (CGRP), is
      released from primary afferent neurons in the trigemino-vascular circulation
      during migraine headache. CGRP at physiological concentrations and possibly via
      stimulation of its selective receptors on T-cells, triggers the secretion of
      cytokines. Cytokines play an important role in several physiological and
      pathological settings such as immunology, inflammation, and pain. OBJECTIVE: To
      investigate plasma levels of pro- and anti-inflammatory cytokines in migraineurs
      and healthy controls. METHODS: We studied 25 migraine patients, during and
      outside attacks, and 18 healthy control subjects measuring plasma levels of IL-6,
      IL-10, tumor necrosis factor alpha (TNFalpha), IL-4, IL-1 beta, and IL-2 using
      ELISA. RESULTS: Circulating levels of IL-10, TNFalpha, and IL-1 beta during
      attacks were significantly higher in comparison to their levels outside attacks
      (P=.0003, P=.03, and P=.05, respectively). IL-10 and TNF serum levels were higher
      in patients studied soon after headache onset and lower over time (P=.004 and
      P=.05). CONCLUSION: Our results suggest that TNFalpha, IL-1 beta, and IL-10 may
      be involved in the pathogenesis of migraine attacks.

PMID- 15985112
TI  - Predictors of a negative response to topiramate therapy in patients with chronic
      migraine.
AB  - OBJECTIVE: To identify variables predictive of a negative response to
      prophylactic therapy with topiramate in patients with chronic migraine.
      BACKGROUND: While certain of the newer antiepileptic drugs (AEDs) have emerged as
      promising or definitely effective therapies for migraine prevention, we continue
      to lack biologic or clinical variables predictive of treatment response to these
      or other widely used prophylactic therapies. METHODS: A consecutive series of 170
      patients with IHS-defined migraine who were experiencing 15 or more days of
      headache per month were treated with topiramate according to a uniform dosing
      protocol. Variables examined for their potential value in predicting treatment
      response included age, gender, prior experience with prophylactic therapy, prior
      experience with divalproex sodium specifically, headache frequency and, if
      present, duration of chronic daily headache (CDH). A positive treatment response
      was defined as a 50% or greater reduction in headache days during the second
      treatment month relative to the patient's pretopiramate baseline. Only patients
      who completed the treatment phase and achieved the 50 mg BID target dose were
      analyzed (efficacy analysis). Each variable prospectively selected was evaluated
      in regards to treatment outcome via a paired t-test, and a multiple regression
      analysis of all variables subsequently was performed. RESULTS: A total of 116
      patients completed at least 60 days of treatment and consequently were available
      for analysis. In the efficacy analysis, 45 (38.8%) of the 116 responded
      positively to topiramate. Neither age nor gender influenced treatment response.
      Those patients with CDH of more than 6 months duration, patients who previously
      had tried and failed more than three prophylactic agents and patients who
      previously had failed to respond to divalproex sodium were more likely to be
      nonresponders, but after multiple regression analysis the only statistically
      significant predictor of a negative treatment response was CDH of more than 6
      months duration (P<.001). CONCLUSIONS: Patients with chronic migraine who are
      treated with topiramate may respond positively at a rate approaching that
      reported from placebo-controlled trials involving topiramate or other AEDs
      administered to less severely afflicted migraineurs. Our analysis suggests that
      patients with chronic migraine least likely to respond to topiramate would be
      those with extensive and negative previous experience with prophylactic therapy,
      previous failure to respond to divalproex sodium, CDH, and, most notably, CDH of
      more than 6 months duration.

PMID- 15985113
TI  - A high incidence of migraine with aura among morbidly obese women.
AB  - INTRODUCTION: Nearly two-thirds of adults in the United States and an increasing
      percentage of the population worldwide are overweight or obese. The relationship
      of obesity to headache has received inadequate attention. We evaluated the
      incidence of headache in a sample of morbidly obese women. METHODS: Morbidly
      obese women, attending the surgical preoperative clinic of Soroka University
      Medical Center for preoperative assessment for laparoscopic gastric banding were
      evaluated using a structured interview and their medical charts were reviewed.
      RESULTS: During a 2-month period, 27 morbidly obese women were interviewed, with
      a mean BMI of 41.07. Ten patients suffered from migraine with aura, three from
      migraine without aura, and four from tension headache. CONCLUSION: The unusually
      high incidence of migraine with aura can be attributed to extraovarian production
      of estrogen and estradiol in the adipose tissue. Further study is indicated to
      explore the therapeutic role of weight loss in headache care.

PMID- 15985114
TI  - The quality of headache treatment in the United States: review and analysis of
      recent data.
AB  - The methods and results of a recent large study of the quality of health care in
      the United States are reviewed with special emphasis on findings specific to
      headache care. The study's implications for educational and quality improvement
      efforts in the headache field are considered. These include (i) the need to teach
      and reinforce fundamental history-taking and physical-examination processes at
      all levels of medical education; (ii) the importance of recognizing serious
      problems of underuse and misuse of proven evaluation and treatment technologies;
      (iii) the desirability of shifting educational resources from simple messages
      that have been adequately absorbed toward more nuanced and targeted educational
      goals; and (iv) the value of novel and unorthodox educational strategies.
      Professional headache societies need to devote considerable resources to address
      the problem of widespread and important deficiencies in simple, fundamental care
      processes for headache.

PMID- 15985115
TI  - Images from headache: thermography redux.

PMID- 15985116
TI  - Transient visual loss, lower extremity monoparesis, and sudden sharp headaches
      precipitated by long car trips.

PMID- 15985117
TI  - Headache and diffuse subarachnoid hyperdensity on head CT following thoracic
      epidural blood patch.

PMID- 15985118
TI  - Migraine with aura related to closure of atrial septal defects.
AB  - A 27-year-old woman had a history of migraine with aura (MWA) since aged 13 years
      with mostly two attacks per year. After transcutaneous closure of a secundum
      atrial septal defect (ASD) she suffered from almost daily recurring migraine
      attacks with prolonged aura symptoms. Exacerbation and new appearance of migraine
      attacks with aura after transcutaneous closure of ASD have been described
      previously.

PMID- 15985119
TI  - Dissecting aneurysm of the basilar artery as a cause of orgasmic headache.
AB  - A 39-year-old woman experienced recurrent, severe bursting headache which was
      abruptly developed at the time of orgasm. Both magnetic resonance angiography and
      conventional angiogram of the brain confirmed dissecting aneurysm of the basilar
      artery. After the neuroradiological intervention using a stent was performed, she
      has been totally free of the orgasmic headache during the follow-up period for
      about one year.

PMID- 15985120
TI  - The effect of weather on headache.

PMID- 15985121
TI  - Brain damage unproven in whiplash associated disorder.

PMID- 15985127
TI  - Determinants of incomplete left ventricular mass regression following aortic
      valve replacement for aortic stenosis.
AB  - OBJECTIVE: Incomplete regression of left ventricular hypertrophy (Abn-LVMI)
      following AVR for aortic stenosis (AS) may decrease long-term survival. In this
      prospective study, we identified the predictors of Abn-LVMI. METHODS: Between
      1990 and 2000, 529 patients undergoing AVR for AS had clinical and hemodynamic
      data collected prospectively. Preoperative and annual postoperative transthoracic
      echos were employed to assess left ventricular mass index (LVMI) and
      hemodynamics. Abn-LVMI was defined as the 75th percentile of the lowest
      postoperative LVMI (>128 mg/m2, n = 133). All other patients were included in the
      normal regression group (N-LVMI). Univariate and multivariable logistic
      regression analyses were used to determine the predictors of Abn-LVMI. RESULTS:
      Preoperative hypertension, diabetes, coronary disease, valve size, mean
      postoperative gradients, effective orifice area, and patient-prosthesis mismatch
      (PPM, indexed EOA <0.60 cm2/m2) did not predict Abn-LVMI. By logistic regression
      the most important positive predictor of Abn-LVMI was the extent of preoperative
      LVMI, with an odds ratio of 37.5 (p < 0.0001). Survival (93.4 +/- 1.8% vs 94.8 +/
      2.3%, p = 0.90) and freedom from NYHA III-IV (75.0 +/- 3.7% vs 76.6 +/- 5.3%, p
      = 0.60) were similar for both groups at 7 years. CONCLUSIONS: Measures of valve
      hemodynamics were not important predictors of incomplete regression of
      hypertrophy. The extent of preoperative hypertrophy was the most important
      predictor, suggesting that earlier surgical intervention may reduce the extent of
      hypertrophy postoperatively. Furthermore, the significance of LV hypertrophy to
      long-term survival must be reassessed, in the absence of scientific evidence.

PMID- 15985128
TI  - Ineffectiveness of local wound anesthesia to reduce postoperative pain after
      median sternotomy.
AB  - Postoperative pain control still represents a major challenge in every surgical
      field. Bupivacaine wound infiltration is frequently used to reduce the pain
      related to the surgical incision itself. In this randomized study, we
      investigated the efficacy of bupivacaine local anesthesia after median sternotomy
      to reduce postoperative pain. Forty-seven patients undergoing major cardiac
      surgery procedures were allocated randomly to group A (bupivacaine wound
      infiltration 0.5%; 10 mL, followed by continuous infusion: 10 mg/24 H) or to
      group C (controls). Extubation time, postoperative arterial blood gases,
      postoperative pain (assessed by means of a visual analog scale), and morphine
      consumption were the endpoints of the study. Patients of group C were extubated
      earlier; blood gases and VAS values were similar in both group. Bupivacaine local
      analgesia did not improve postoperative pain control after median sternotomy.

PMID- 15985129
TI  - Blood pressure changes after aortic coarctation surgery performed in adulthood.
AB  - OBJECTIVE: The aim of this study was to assess the effect of aortic coarctation
      surgery in adult patients on arterial blood pressure in the early postoperative
      period. METHODS: Ninety-three adult patients (61 male, 32 female) aged 15-43
      years who had operation since 1962 for aortic coarctation in Siyami Ersek
      Cardiovascular Surgery Center were retrospectively evaluated. Tube graft
      interposition was done in 31 patients; resection and end-to-end anastomosis were
      performed in 32 patients; 24 patients had undergone pathchplasty; and 6 patients
      by-pass shunting performed. The effect of surgery on the blood pressure was
      investigated. RESULTS: The mean systolic and diastolic blood pressure
      significantly reduced after operation (systolic 193.6 +/- 33.7 mmHg vs 147.4 +/-
      22.0 mmHg, diastolic 99.8 +/- 17.9 mmHg vs 82.0 +/- 10.8 mmHg). From 93 patients
      (all with hypertension) 54 (58%) became normotensive after operation according to
      VIth Joint National Committee classification. The number of normotensive patients
      after operation was 28 (of 37) for 15-19 years age group, 14 (of 23) for the 20
      24 years age group, 4 (of 16) for 25-29 years age group, 6 (of 11) for 30-34
      years age group, and 2 (of 6) for the over 35 years old age group. CONCLUSION:
      The diastolic and systolic blood pressures reduce significantly in the adult
      patients operated for aortic coarctation. On the other hand, persistent
      hypertension seemed to increase in the older age groups in spite of the surgery.

PMID- 15985130
TI  - Comparison of volume study by left ventriculography and gated SPECT in
      endoventricular circular patchplasty.
AB  - Although quantitative gated SPECT (QGS) is widely used for left ventricular (LV)
      volume study, its accuracy is not established for those who have a large
      myocardial infarction scar or who had endoventricular circular patch plasty
      (EVCPP). Therefore, we compared LV volumes and LVEF calculated by QGS and those
      calculated by left ventriculography (LVG) before and after EVCPP. Sixteen
      patients (13 men and 3 women, mean age 67 +/- 9.5 years) were treated with EVCPP
      for postinfarction LV dyskinetic and/or akinetic scar. All patients were
      evaluated with both QGS and LVG before and after surgery. QGS was performed using
      eight frames per cardiac cycle, 1 hour after 740 MBq (99 m)Tc-tetrofosimin was
      administered. LVG images were acquired at a frame rate of 30 frames per second in
      the right anterior oblique 30-degree projection. We compared LV end-diastolic
      volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF)
      between QGS and LVG. There was an excellent linear correlation between QGS and
      LVG in LVEDV (preoperative; r = 0.87, postoperative; r = 0.94), LVESV
      (preoperative; r = 0.95, postoperative; r = 0.89), and LVEF (preoperative; r =
      0.73, postoperative; r = 0.81) before and after EVCPP. However, both preoperative
      LV volumes and postoperative LVEF calculated from QGS gave a smaller value than
      those calculated from LVG. Postoperative volume data by QGS was much close to
      LVG. The present study indicated that volume study by QGS is very useful to
      evaluate the LV function after EVCPP. However, we should pay attention to those
      facts.

PMID- 15985131
TI  - Lack of durability of surgical arterialization of coronary veins for the
      treatment of ischemic heart disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Coronary venous arterialization with a catheter
      based system has renewed interest in this therapy for the revascularization of
      areas that cannot be treated by conventional coronary artery bypass graft or
      angioplasty. However, the durability of the venous system to supply arterial
      pulsatile blood is still a matter of debate. METHODS: We report the outcome of
      four patients that underwent elective coronary artery bypass grafting of the left
      coronary system and in addition had selective arterialization of the posterior
      vein due to ungraftable poor distal vessels of the right coronary artery.
      Complete revascularization of the left side was achieved using the left internal
      mammary artery and the left radial artery. One vein graft was anastomosed to the
      postero-inferior vein in three cases and to two postero-inferior veins in the
      fourth case. RESULTS: No perioperative complications were observed and after 24
      months of follow-up; all patients were angina free and without any symptoms of
      heart failure. The 24 months follow-up also showed (i) normal exercise test in
      all patients, (ii) ischemic changes in dobutamine stress echocardiography in the
      areas corresponding with the venous arterialization in two cases, and (iii)
      occlusion of the graft supplying the coronary veins in the three patients that
      accepted to undergo selective angiogram. CONCLUSION: In conclusion, these results
      indicate that arterialization of the coronary veins is not durable and that it is
      unlikely that this strategy is a useful technique for the revascularization of
      the ischemic myocardium.

PMID- 15985132
TI  - Risk factor analysis of hospital mortality in patients with endocarditis with
      ring abscess.
AB  - BACKGROUND: Endocarditis associated with ring abscess is a pathology with high
      morbidity and mortality. AIM OF THE STUDY: The purpose of this study was to
      analyze hospital mortality risk factors in patients with ring abscess due to
      endocarditis. METHODS: From January 1982 to December 2000, 104 patients underwent
      surgical intervention at the Heart Institute of the University of Sao Paulo
      Medical School for valve endocarditis with ring abscess. The age ranged from 6
      years to 73 years, with an average of 40.3 years and 72.1% were male. According
      to NYHA functional class (FC), 12 (11.5%) were in FC II, 62 (59.6%) in FC III,
      and 30 (28.9%) in FC IV. Seventy-seven (74.0%) patients had endocarditis on a
      bioprosthesis, 58 (55.8%) in the aortic position and 19 (18.3%) in the mitral
      position. Twenty-nine (26.9%) patients had atrioventricular blockage prior to the
      operation. Univariate analysis was performed comparing variables and hospital
      mortality with a level of significance of 5%. Multivariate analysis was performed
      by logistic regression. RESULTS: The hospital mortality was 19.2% (20 patients).
      Univariate analysis showed that atrioventricular blockage, age, and prosthetic
      valve endocarditis significantly influenced hospital mortality. Multivariate
      analysis identified atrioventricular blockage as an independent predictor of
      hospital mortality. CONCLUSIONS: Preoperative atrioventricular blockage is an
      independent risk factor for hospital mortality in the surgical treatment of
      endocarditis with ring abscess.

PMID- 15985133
TI  - Left ventricular unloading with an assist device results in receptor
      relocalization as well as increased beta-adrenergic receptor numbers: are these
      changes indications for outcome?
AB  - BACKGROUND: The use of left ventricular (LV) assist devices (LVADs) can improve
      performance and recovery of failing human hearts. AIM: Following our alpha
      adrenergic receptor work, we hypothesized that mechanical unloading in patients
      with low output syndrome and LV failure would yield similar results with beta
      adrenergic receptors ((beta)AR), that being increased numbers and intra-myocytic
      relocalization. METHODS: (beta)AR density and localization were investigated by
      fluorescence deconvolution microscopy and compared at LVAD insertion and removal
      in 13 heart failure patients, the patients therefore acting as their own control.
      (beta)AR densities and distribution were determined in snap frozen sections of
      human core biopsy left ventricular apical tissue. Samples were probed with tagged
      CGP 12177 for visualization of (beta)AR and challenged with cold agonists and
      antagonists. (beta)AR density was measured by two independent methods.
      Localization of receptors was examined in reconstructed, deconvoluted, stacked
      section images. RESULTS: There was an increase in (beta)AR density following
      ventricular unloading in most of the patients, and also significant normalization
      in the location of the receptors in the myocardium comparing pre- and post-LVAD
      tissue. CONCLUSIONS: These findings suggest that supporting an ailing heart via
      unloading initiates mechanisms and pathways responsible for myocardial recovery
      and repair. With appropriate pharmacological support, patients with LVAD might
      recover to the point where they no longer depend on eventual organ
      transplantation, and (beta)AR number, type, and distribution in pre-LVAD
      myocardial tissue, could predict outcome with regard to recovery, repair, and
      improvement in cardiac function.

PMID- 15985134
TI  - Aspartate and glutamate-enriched cardioplegia in left ventricular dysfunction.
AB  - BACKGROUND: The effects of exogenous L-aspartate and L-glutamate-enriched
      cardioplegia on postoperative left ventricular functions after coronary artery
      bypass surgery in patients with moderate left ventricular dysfunction (left
      ventricular ejection fraction [LVEF]= 30-40%) were studied. METHODS: In this
      prospective randomized study, 22 patients with moderate left ventricular
      dysfunction (mean LVEF = 37.27%+/- 3.43%), who underwent elective coronary artery
      bypass surgery, were examined. Isothermic substrate-enriched [L-aspartate and L
      glutamate (13 mmol/L)] blood cardioplegia was used in 11 patients (Group AG), and
      cardioplegia including only potassium and sodium bicarbonate was used in 11
      patients (Group C). All hemodynamic parameters for left and right heart were
      studied in both groups. Total perfusion time was 126.63 +/- 44.91 minutes versus
      114.81 +/- 43.66 minutes (p = 0.54). The aortic cross-clamp time was 77.09 +/-
      28.02 minutes versus 67.81 +/- 22.77 minutes (p = 0.4), respectively. The amount
      of cardioplegic solutions were 7218.2 +/- 3043.6 mL versus 5454.5 +/- 3048.1 mL
      (p = 0.167). Mean number of distal anastomosis were 3 +/- 0.89 versus 2.9 +/- 0.7
      (p = 0.793). RESULTS: There was no difference between both groups in intra- and
      postoperative periods. In coronary sinus blood gas measures, myocardial acidosis
      caused by the aortic cross-clamp was found to be more severe in the Group C, but
      delta pH (0.12 +/- 0.14 vs. 0.092 +/- 0.058; p = 0.613) and delta lactate (1.39
      +/- 1.03 vs. 1.62 +/- 0.85; p = 0.579) were similar in both groups. Free oxygen
      radical production caused by aortic cross-clamp was significant in the Group C.
      Not all myocardial enzymes, but Troponin-T levels were found higher in control
      group than the study group (0.6 +/- 0.36 vs. 0.36 +/- 0.25; p = 0.1).
      CONCLUSIONS: Although L-aspartate and L-glutamate favor myocardial metabolic
      functions, they do not have any affect on myocardial functional recovery in
      patients with moderate left ventricular dysfunction.

PMID- 15985135
TI  - Coronary bypass procedures in patients with renal artery stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: We present our experience on patients with renal
      artery stenosis undergoing myocardial revascularization procedures. METHODS:
      Eighteen patients with varying degrees of renal artery stenosis were operated for
      coronary artery bypass grafting between 1996 and 2003. The overall incidence was
      0.15%. There were nine male and nine female patients with a mean age of 62 +/-
      8.2 (40-72 years). Four had bilateral and eight had significant unilateral (>50%)
      renal artery stenoses. Preoperatively, three patients had renal arterial
      intervention (stenting), and one patient was on hemodialysis. The mean
      preoperative creatinine value was 2.6 +/- 2.7 mg/dL (range 0.7 to 9.3). The
      patients were followed medically: two patients underwent off-pump coronary bypass
      grafting and the others were operated on-pump. RESULTS: There was only one
      mortality and two patients required hemodialysis postoperatively. The
      postoperative mean creatinine values were 3.4 +/- 4.9 mg/dL (range 1.0 to 12.5).
      No electrolyte imbalances were noted except that one case revealed a transient
      metabolic acidosis. Five patients required inotropic support with dopamine and
      two needed diuretic infusions. Only five patients demonstrated a refractory hyper
      tensive period postoperatively. CONCLUSIONS: The concomitant correction of renal
      artery stenosis with CABG is usually not necessary, but the principles for
      renovascular diseases must be kept in mind and individually oriented strategies
      must be planned.

PMID- 15985136
TI  - Simultaneous antegrade/retrograde normothermic perfusion with blood (beating
      heart) for aortic root replacement in acute type-a dissection of the aorta.
AB  - A new technique of myocardial protection was utilized in performing surgery for
      acute type-A dissection involving the aortic valve, requiring replacement of the
      root. Simultaneous antegrade and retrograde perfusion of the heart with
      normothermic blood at high flows allows for safe and precise surgery, without
      concerns for the period of aortic clamping, since ischemia is eliminated
      altogether.

PMID- 15985137
TI  - Left superior vena cava draining into the left atrium, associated with partial
      anomalous pulmonary venous connection: surgical correction.
AB  - A persistent left superior vena cava draining into the left atrium may produce a
      symptomatic right-to-left shunt. Although intra-atrial rerouting techniques, in
      patients with no connecting vein, have proved to be reliable and successful, in
      many cases the extracardiac repair is preferable. We report a case of a 5-month
      old patient with a not connected left superior vena cava draining into the left
      atrium, associated with atrial septal defect and partial anomalous pulmonary
      venous connection. The correction has been achieved by rerouting the pulmonary
      venous return into the left atrium and by transposition of the left vena cava on
      the right appendage.

PMID- 15985138
TI  - Posttraumatic tricuspid insufficiency successfully repaired by conventional
      technique.
AB  - A 22-year-old man developed exertional dyspnea 2 years after blunt chest trauma
      due to a horse kick. Preoperative echocardiography showed severe tricuspid
      insufficiency (TI) caused by chordal rupture and prolapse of the anterior
      leaflet. A novel repair technique, the "clover technique," was applied, but was
      unsuccessful in this case. The valve was then repaired successfully using
      conventional techniques, that is, insertion of an artificial chordae, plication
      of the prolapsing leaflet, and DeVega's annuloplasty. We present here a brief
      review of posttraumatic TI, and discuss effective and less expensive techniques
      for repair.

PMID- 15985140
TI  - Successful resection of cardiac metastatic liposarcoma extending into the SVC,
      right atrium, and right ventricle.
AB  - Cardiac metastatic liposarcoma is a rare tumor. We report a case of successful
      resection of a cardiac metastatic liposarcoma extending into the superior vena
      cava (SVC), right atrium, and right ventricle. Using cardiopulmonary bypass (CPB)
      by venous cannulation of the upper portion of the SVC and inferior vena cava
      (IVC), the intracardiac tumor was completely resected. Surgical resection with
      the addition of radiotherapy prolonged the patient's life.

PMID- 15985139
TI  - Triple valve repair for rheumatic heart disease.
AB  - The onset of the clinical expression of rheumatic heart disease (RHD) is
      variable. Exercise or other states that necessitate increased cardiac output
      often precipitate symptoms. Mitral stenosis (MS) is present in 25% of patients
      with RHD, and 40% of patients have concomitant MS and mitral regurgitation. About
      two third of patients with MS have concurrent aortic insufficiency. Pulmonary and
      tricuspid insufficiency may occur from rheumatic involvement of these valves, or
      secondary to dilatation of valve annuli from pulmonary hypertension secondary to
      mitral and/or aortic valve disease. Pregnancy is associated with many hemodynamic
      changes including expanded intravascular volume, tachycardia, increased
      intracardiac dimensions, and valvular regurgitation. We report a case of a young
      female who developed flash pulmonary edema during parturition and was found to
      have abnormal rheumatic involvement of her aortic, mitral, and tricuspid valves.
      Successful triple valve repair was performed in a single operation. A review of
      rheumatic valvular abnormalities, and literature supporting multivalvular repair
      for rheumatic heart disease is provided.

PMID- 15985141
TI  - Off-pump myocardial revascularization in a diabetic patient with severe
      hemophilia B and impaired left ventricular function: hematological and operative
      strategies.
AB  - Coronary surgery with diabetes and severe hemophilia B is a challenging situation
      requiring specific and adequate therapeutic considerations. We herein report the
      case of a 52-year-old diabetic patient with severe factor IX deficiency and
      impaired ventricular function, who was scheduled for myocardial revascularization
      because of exertional angina and recurrent myocardial infarctions following
      infusions of factor IX concentrate. The patient underwent a successful off-pump
      direct myocardial revascularization with neither hemorrhagic nor thrombotic
      complications. Hematological protocols and operative strategies are assessed and
      discussed.

PMID- 15985143
TI  - Absence of right superior vena cava and aortic annular hypoplasia in a patient
      with Turner's syndrome.
AB  - Cardiovascular abnormalities are frequently encountered in patients with Turner's
      syndrome. These include coarctation of the aorta, bicuspid aortic valve, aortic
      root dilatation, atrial and ventricular septal defects, but absence of the right
      superior vena cava (SVC) in visceroatrial situs solitus is extremely rare. We
      report absence of the right SVC and congenital aortic annular hypoplasia with
      bicuspid aortic valve stenosis in a patient with Turner's syndrome. Aortic root
      extension with prosthetic valve replacement was performed and absent right SVC,
      which was detected incidentally during operation, is confirmed by postoperative
      venous angiogram.

PMID- 15985142
TI  - Surgical closure of combined symptomatic patent foramen ovale and atrial septum
      aneurysm for prevention of recurrent cerebral emboli.
AB  - BACKGROUND: Patients with patent foramen ovale (PFO) have an undefined but
      certainly considerable risk of repeated cerebral ischemia due to paradoxical
      embolism. Especially, if a cerebrovascular event has already occurred and the
      combination with an atrial septum aneurysm (ASA) is present this risk increases
      tremendously. The aim of this study was to demonstrate that surgical closure of
      PFO in combination with an ASA is safe and useful in preventing recurrent
      strokes. METHODS: Ten patients with previous cerebral ischemia, proven by CT or
      MRI, and PFO in combination with an ASA were prospectively scheduled for surgical
      closure. Patients with extracardiac sources of embolic disease were excluded from
      this study. However, one patient suffered from a hypercoagulability syndrome.
      RESULTS: All patients (mean age 35.5 +/- 19.1 years) underwent direct suture of
      the PFO and plication of the ASA with the aid of cardiopulmonary bypass and
      cardioplegic arrest (n = 3) or ventricular fibrillation (n = 7). Mean operation
      time was 123.1 +/- 20.2 minutes; mean bypass time was 34.5 +/- 9.9 minutes. There
      was no mortality or significant postoperative morbidity. Mean hospital stay was
      5.1 +/- 1.5 days. During a follow-up of >4 years, no recurrent stroke or
      transient ischemic attack occurred and no patient received anticoagulation
      therapy. CONCLUSION: Our data suggest that surgical closure of PFO in combination
      with ASA in patients with previous stroke is safe and efficacious to prevent
      recurrent strokes and avoids lifelong anticoagulation.

PMID- 15985144
TI  - Steal phenomenon with kinked graft caused a loss of viability in a dialysis
      patient.
AB  - A 74-year-old man with chronic renal failure under hemodialysis via the left
      upper extremity underwent an off-pump coronary artery bypass (OPCAB). The left
      internal thoracic artery (LITA), which was harvested in a skeletonized manner,
      was anastomosed to the left anterior descending artery (LAD). Postoperatively, he
      complained of chest pain only during dialysis. Angiography revealed a kinking in
      the LITA. However, myocardial scintigraphy revealed no ischemia. One year after
      OPCAB, left ventriculography revealed akinesis and myocardial scintigraphy
      revealed no viability in the anterior wall. This suggested that the viability was
      lost due to graft kinking and steal phenomenon during hemodialysis. If the length
      of the skeletonized ITA graft is redundant, kinking of the graft rarely occurs
      after the chest is closed. We also suggest that to avoid the kinking of the ITA
      graft, fibrin glue should be used to paste the ITA graft running in a gentle
      curve.

PMID- 15985145
TI  - Aortic valve replacement for a patient with glucose-6-phosphate dehydrogenase
      deficiency and autoimmune hemolytic anemia.
AB  - Autoimmune hemolytic anemia and deficiency of glucose-6-phosphate deyhdrogenase
      (G6PD) result in severe hemolysis with different mechanisms. In patients with
      both pathologies, the effects of cardiopulmonary bypass on red blood cells and
      thrombocytes demand special care before and after open heart surgery. We
      evaluated the preoperative management and postoperative care of a patient with
      severe aortic insufficiency associated with G6PD deficiency and autoimmune
      hemolytic anemia who underwent aortic valve replacement.

PMID- 15985146
TI  - Intravenous uterine leiomyosarcomatosis with intracardial extension.
AB  - Uterine leiomyosarcoma is a rare malignant tumor of smooth muscle origin. We
      describe the case of a 64-year-old female with intravenous uterine
      leiomyosarcomatosis with the extension of the tumor mass into the inferior vena
      cava and right atrium. As initial tissue diagnosis of the tumor obtained from the
      uterine and right atrial masses suggested intravenous leiomyomatosis, surgical
      resection was carried out using a one-stage procedure via a laparotomy and median
      sternotomy with cardiopulmonary bypass and circulatory arrest. Subsequent
      histology revealed uterine leiomyosarcoma with an intravenous spread, which to
      our knowledge is only the second case that has been described.

PMID- 15985147
TI  - Ductus arteriosus aneurysm in an adult patient presenting with hoarseness.
AB  - Aneurysm of the ductus arteriosus is a rare diagnosis, with most cases found in
      the pediatric population. The unusual adult cases reported in the literature have
      been associated with high morbidity and a surgical repair has been recommended.
      We report a case of a 60-year-old man who presented with hoarseness secondary to
      a ductus arteriosus aneurysm and underwent a repair of this abnormality via a
      left posterolateral thoracotomy utilizing partial cardiopulmonary bypass.

PMID- 15985148
TI  - Infective endocarditis in a hancock bioprosthetic heart valve.
AB  - Contemporary prosthetic heart valves (PHV) are a good mode of treatment of
      valvular heart disease. They last for an average of 5 to 10 years and
      bioprostheses fail due to the tissue degeneration. Infective endocarditis of the
      prosthetic valve is a relatively rare complication occurring in 0.5% to 1% of
      cases per year, and its late occurrence is even less common. Patients with PHV
      who undergo interventional or surgical procedures under adequate antibiotic
      coverage, infective endocarditis should not occur. We present a case of a 54-year
      old woman who developed infective endocarditis on a porcine bioprosthesis,
      implanted 15 years earlier. The microorganism was Streptococcus viridans and the
      vegetations were surprisingly large and led to prosthesis obstruction.

PMID- 15985149
TI  - Techniques, complications, and pitfalls of endoscopic saphenectomy for coronary
      artery bypass grafting surgery.
AB  - OBJECTIVES: The purpose of the present paper is to discuss technical features of
      endoscopic saphenectomy with CO2 insufflation for CABG surgery and to highlight
      special situations in which to avoid potential pitfalls that may be encountered.
      METHODS: The initial section describes the approaches used with endoscopic
      saphenectomy with insufflation of CO2 at the Montreal Heart Institute and the
      Wausau Heart Institute, which can be used by operators with different levels of
      experience. The following sections expose numerous intraoperative tricks and
      maneuvers to facilitate the procedure. Specific situations associated with
      increased difficulty are reviewed such as the obese patient, venous
      insufficiency, vein tethered to the dermis, and double venous systems.
      Complications specific to the technique such as gas embolism, tunnelitis, and
      hematomas are discussed and preventive measures are proposed to avoid the rare
      morbidity associated with endoscopic harvesting. Preparation of the patient as
      well as monitoring during the intervention are also reviewed. RESULTS: Adherence
      to the comprehensive approach presented in this text should to ensure retrieval
      of high-quality grafts with a low complication rate providing patients with the
      full benefits, both cardiac and functional, of this minimally invasive technique
      of saphenous vein harvesting for CABG.

PMID- 15985150
TI  - Guanine-nucleotide exchange on ribosome-bound elongation factor G initiates the
      translocation of tRNAs.
AB  - BACKGROUND: During the translation of mRNA into polypeptide, elongation factor G
      (EF-G) catalyzes the translocation of peptidyl-tRNA from the A site to the P site
      of the ribosome. According to the 'classical' model, EF-G in the GTP-bound form
      promotes translocation, while hydrolysis of the bound GTP promotes dissociation
      of the factor from the post-translocation ribosome. According to a more recent
      model, EF-G operates like a 'motor protein' and drives translocation of the
      peptidyl-tRNA after GTP hydrolysis. In both the classical and motor protein
      models, GDP-to-GTP exchange is assumed to occur spontaneously on 'free' EF-G even
      in the absence of a guanine-nucleotide exchange factor (GEF). RESULTS: We have
      made a number of findings that challenge both models. First, free EF-G in the
      cell is likely to be in the GDP-bound form. Second, the ribosome acts as the GEF
      for EF-G. Third, after guanine-nucleotide exchange, EF-G in the GTP-bound form
      moves the tRNA2-mRNA complex to an intermediate translocation state in which the
      mRNA is partially translocated. Fourth, subsequent accommodation of the tRNA2
      mRNA complex in the post-translocation state requires GTP hydrolysis. CONCLUSION:
      These results, in conjunction with previously published cryo-electron microscopy
      reconstructions of the ribosome in various functional states, suggest a novel
      mechanism for translocation of tRNAs on the ribosome by EF-G. Our observations
      suggest that the ribosome is a universal guanosine-nucleotide exchange factor for
      EF-G as previously shown for the class-II peptide-release factor 3.

PMID- 15985151
TI  - Movement in ribosome translocation.
AB  - Translocation of peptidyl-tRNA and mRNA within the ribosome during protein
      synthesis is promoted by the elongation factor EF-G and by the hydrolysis of GTP.
      A new study reports that EF-G binds to ribosomes as an EF-G.GDP complex and that
      GTP is exchanged for GDP on the ribosome. Together with cryo-electron microscopy,
      this unexpected finding helps clarify the role of GTP in translocation.

PMID- 15985152
TI  - The GTPase switch in ribosomal translocation.

PMID- 15985153
TI  - An inactivated nuclease-like domain in RecC with novel function: implications for
      evolution.
AB  - BACKGROUND: The PD-(D/E)xK superfamily, containing a wide variety of other exo-
      and endonucleases, is a notable example of general function conservation in the
      face of extreme sequence and structural variation. Almost all members employ a
      small number of shared conserved residues to bind catalytically essential metal
      ions and thereby effect DNA cleavage. The crystal structure of the RecBCD
      prokaryotic DNA repair machinery shows that RecB contains such a nuclease domain
      at its C-terminus. The RecC C-terminal region was reported as having a novel
      fold. RESULTS: The RecC C-terminal region can be divided into an alpha/beta
      domain and a smaller alpha-helical bundle domain. Here we show that the
      alpha/beta domain is homologous to the RecB nuclease domain but lacks the
      features necessary for catalysis. Instead, the domain has a novel function within
      the nuclease superfamily--providing a hoop through which single-stranded DNA
      passes. Comparison with other structures of nuclease domains bound to DNA reveals
      strikingly different modes of ligand binding. The alpha-helical bundle domain
      contributes the pin which splits the DNA duplex. CONCLUSION: The demonstrated
      homology of RecB and RecC shows how evolution acted to produce the present RecBCD
      complex through aggregation of new domains as well as functional divergence and
      structural redeployment of existing domains. Distantly homologous nuclease(-like)
      domains bind DNA in highly diverse manners.

PMID- 15985155
TI  - Regulation of mouse hepatic genes in response to diet induced obesity, insulin
      resistance and fasting induced weight reduction.
AB  - BACKGROUND: Obesity is associated with insulin resistance that can often be
      improved by caloric restriction and weight reduction. Although many physiological
      changes accompanying insulin resistance and its treatment have been
      characterized, the genetic mechanisms linking obesity to insulin resistance are
      largely unknown. We used DNA microarrays and RT-PCR to investigate significant
      changes in hepatic gene transcription in insulin resistant, diet-induced obese
      (DIO)-C57/BL/6J mice and DIO-C57/BL/6J mice fasted for 48 hours, whose weights
      returned to baseline levels during these conditions. RESULTS: Transcriptional
      profiling of hepatic mRNA revealed over 1900 genes that were significantly
      perturbed between control, DIO, and fasting/weight reduced DIO mice. From this
      set, our bioinformatics analysis identified 41 genes that rigorously discriminate
      these groups of mice. These genes are associated with molecular pathways involved
      in signal transduction, and protein metabolism and secretion. Of particular
      interest are genes that participate in pathways responsible for modulating
      insulin sensitivity. DIO altered expression of genes in directions that would be
      anticipated to antagonize insulin sensitivity, while fasting/weight reduction
      partially or completely normalized their levels. Among these discriminatory
      genes, Sh3kbp1 and RGS3, may have special significance. Sh3kbp1, an endogenous
      inhibitor of PI-3-kinase, was upregulated by high-fat feeding, but normalized to
      control levels by fasting/weight reduction. Because insulin signaling occurs
      partially through PI-3-kinase, increased expression of Sh3kbp1 by DIO mice may
      contribute to hepatic insulin resistance via inhibition of PI-3-kinase. RGS3, a
      suppressor of G-protein coupled receptor generation of cAMP, was repressed by
      high-fat feeding, but partially normalized by fasting/weight reduction. Decreased
      expression of RGS3 may augment levels of cAMP and thereby contribute to
      increased, cAMP-induced, hepatic glucose output via phosphoenolpyruvate
      carboxykinase (PCK1), whose mRNA levels were also elevated. CONCLUSION: These
      findings demonstrate that hepatocytes respond to DIO and weight reduction by
      controlling gene transcription in a variety of important molecular pathways.
      Future studies that characterize the physiological significance of the identified
      genes in modulating energy homeostasis could provide a better understanding of
      the mechanisms linking DIO with insulin resistance.

PMID- 15985154
TI  - Structural organization and interactions of transmembrane domains in tetraspanin
      proteins.
AB  - BACKGROUND: Proteins of the tetraspanin family contain four transmembrane domains
      (TM1-4) linked by two extracellular loops and a short intracellular loop, and
      have short intracellular N- and C-termini. While structure and function analysis
      of the larger extracellular loop has been performed, the organization and role of
      transmembrane domains have not been systematically assessed. RESULTS: Among 28
      human tetraspanin proteins, the TM1-3 sequences display a distinct heptad repeat
      motif (abcdefg)n. In TM1, position a is occupied by structurally conserved bulky
      residues and position d contains highly conserved Asn and Gly residues. In TM2,
      position a is occupied by conserved small residues (Gly/Ala/Thr), and position d
      has a conserved Gly and two bulky aliphatic residues. In TM3, three a positions
      of the heptad repeat are filled by two leucines and a glutamate/glutamine
      residue, and two d positions are occupied by either Phe/Tyr or Val/Ile/Leu
      residues. No heptad motif is apparent in TM4 sequences. Mutations of conserved
      glycines in human CD9 (Gly25 and Gly32 in TM1; Gly67 and Gly74 in TM2) caused
      aggregation of mutant proteins inside the cell. Modeling of the TM1-TM2 interface
      in CD9, using a novel algorithm, predicts tight packing of conserved bulky
      residues against conserved Gly residues along the two helices. The homodimeric
      interface of CD9 was mapped, by disulfide cross-linking of single-cysteine
      mutants, to the vicinity of residues Leu14 and Phe17 in TM1 (positions g and c)
      and Gly77, Gly80 and Ala81 in TM2 (positions d, g and a, respectively). Mutations
      of a and d residues in both TM1 and TM2 (Gly25, Gly32, Gly67 and Gly74), involved
      in intramolecular TM1-TM2 interaction, also strongly diminished intermolecular
      interaction, as assessed by cross-linking of Cys80. CONCLUSION: Our results
      suggest that tetraspanin intra- and intermolecular interactions are mediated by
      conserved residues in adjacent, but distinct regions of TM1 and TM2. A key
      structural element that defines TM1-TM2 interaction in tetraspanins is the
      specific packing of bulky residues against small residues.

PMID- 15985156
TI  - Multiple sequence alignments of partially coding nucleic acid sequences.
AB  - BACKGROUND: High quality sequence alignments of RNA and DNA sequences are an
      important prerequisite for the comparative analysis of genomic sequence data.
      Nucleic acid sequences, however, exhibit a much larger sequence heterogeneity
      compared to their encoded protein sequences due to the redundancy of the genetic
      code. It is desirable, therefore, to make use of the amino acid sequence when
      aligning coding nucleic acid sequences. In many cases, however, only a part of
      the sequence of interest is translated. On the other hand, overlapping reading
      frames may encode multiple alternative proteins, possibly with intermittent non
      coding parts. Examples are, in particular, RNA virus genomes. RESULTS: The
      standard scoring scheme for nucleic acid alignments can be extended to
      incorporate simultaneously information on translation products in one or more
      reading frames. Here we present a multiple alignment tool, codaln, that
      implements a combined nucleic acid plus amino acid scoring model for pairwise and
      progressive multiple alignments that allows arbitrary weighting for almost all
      scoring parameters. Resource requirements of codaln are comparable with those of
      standard tools such as ClustalW. CONCLUSION: We demonstrate the applicability of
      codaln to various biologically relevant types of sequences (bacteriophage
      Levivirus and Vertebrate Hox clusters) and show that the combination of nucleic
      acid and amino acid sequence information leads to improved alignments. These, in
      turn, increase the performance of analysis tools that depend strictly on good
      input alignments such as methods for detecting conserved RNA secondary structure
      elements.

PMID- 15985157
TI  - The central role of vascular extracellular matrix and basement membrane
      remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded.
AB  - The vascular endothelial basement membrane and extra cellular matrix is a
      compilation of different macromolecules organized by physical entanglements,
      opposing ionic charges, chemical covalent bonding, and cross-linking into a
      biomechanically active polymer. These matrices provide a gel-like form and
      scaffolding structure with regional tensile strength provided by collagens,
      elasticity by elastins, adhesiveness by structural glycoproteins, compressibility
      by proteoglycans--hyaluronans, and communicability by a family of integrins,
      which exchanges information between cells and between cells and the extracellular
      matrix of vascular tissues. Each component of the extracellular matrix and
      specifically the capillary basement membrane possesses unique structural
      properties and interactions with one another, which determine the separate and
      combined roles in the multiple diabetic complications or diabetic opathies.
      Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel
      companion (atheroscleropathy) are associated with multiple metabolic toxicities
      and chronic injurious stimuli. The adaptable quality of a matrix or form
      genetically preloaded with the necessary information to communicate and respond
      to an ever-changing environment, which supports the interstitium, capillary and
      arterial vessel wall is individually examined.

PMID- 15985158
TI  - The polymorphic nature of the human dopamine D4 receptor gene: a comparative
      analysis of known variants and a novel 27 bp deletion in the promoter region.
AB  - BACKGROUND: The human dopamine D4 receptor (DRD4) is a candidate gene of great
      interest in molecular studies of human personality and psychiatric disorders.
      This gene is unique in having an exceptionally high amount of polymorphic sites
      both in the coding and in the promoter region. RESULTS: We report the
      identification of a new 27 bp deletion starting 524 bp upstream of the initiation
      codon (27 bp del) of the dopamine D4 receptor (DRD4) gene, in the close vicinity
      of the -521C>T SNP. The presence of the 27 bp deletion leads to the misgenotyping
      of the -616C>G SNP by the Sau96 I RFLP method, thus the genotype determination of
      the mutation is of additional importance. The frequency of this novel sequence
      variation is considerably low (allele frequency is = 0.16%), as no homozygotes,
      and only 3 heterozygote carriers were found in a healthy, unrelated Caucasian
      sample (N = 955). CONCLUSION: Remarkably, the deleted region contains consensus
      sequences of binding sites for several known transcription factors, suggesting
      that the different alleles may affect the transcriptional regulation of the gene.
      A comparison of methods and results for the allelic variations of the DRD4 gene
      in various ethnic groups is also discussed, which has a high impact in
      psychiatric genetic studies.

PMID- 15985159
TI  - Mathematical modelling to centre low tidal volumes following acute lung injury: a
      study with biologically variable ventilation.
AB  - BACKGROUND: With biologically variable ventilation [BVV--using a computer
      controller to add breath-to-breath variability to respiratory frequency (f) and
      tidal volume (VT)] gas exchange and respiratory mechanics were compared using the
      ARDSNet low VT algorithm (Control) versus an approach using mathematical
      modelling to individually optimise VT at the point of maximal compliance change
      on the convex portion of the inspiratory pressure-volume (P-V) curve
      (Experimental). METHODS: Pigs (n = 22) received pentothal/midazolam anaesthesia,
      oleic acid lung injury, then inspiratory P-V curve fitting to the four-parameter
      logistic Venegas equation F(P) = a + b[1 + e-(P-c)/d]-1 where: a = volume at
      lower asymptote, b = the vital capacity or the total change in volume between the
      lower and upper asymptotes, c = pressure at the inflection point and d = index
      related to linear compliance. Both groups received BVV with gas exchange and
      respiratory mechanics measured hourly for 5 hrs. Postmortem bronchoalveolar fluid
      was analysed for interleukin-8 (IL-8). RESULTS: All P-V curves fit the Venegas
      equation (R2 > 0.995). Control VT averaged 7.4 +/- 0.4 mL/kg as compared to
      Experimental 9.5 +/- 1.6 mL/kg (range 6.6 - 10.8 mL/kg; p < 0.05). Variable VTs
      were within the convex portion of the P-V curve. In such circumstances, Jensen's
      inequality states "if F(P) is a convex function defined on an interval (r, s),
      and if P is a random variable taking values in (r, s), then the average or
      expected value (E) of F(P); E(F(P)) > F(E(P))." In both groups the inequality
      applied, since F(P) defines volume in the Venegas equation and (P) pressure and
      the range of VTs varied within the convex interval for individual P-V curves.
      Over 5 hrs, there were no significant differences between groups in minute
      ventilation, airway pressure, blood gases, haemodynamics, respiratory compliance
      or IL-8 concentrations. CONCLUSION: No difference between groups is a consequence
      of BVV occurring on the convex interval for individualised Venegas P-V curves in
      all experiments irrespective of group. Jensen's inequality provides theoretical
      proof of why a variable ventilatory approach is advantageous under these
      circumstances. When using BVV, with VT centred by Venegas P-V curve analysis at
      the point of maximal compliance change, some leeway in low VT settings beyond
      ARDSNet protocols may be possible in acute lung injury. This study also shows
      that in this model, the standard ARDSNet algorithm assures ventilation occurs on
      the convex portion of the P-V curve.

PMID- 15985160
TI  - Household cost-benefit equations and sustainable universal childhood
      immunisation: a randomised cluster controlled trial in south Pakistan
      [ISRCTN12421731].
AB  - BACKGROUND: Household decision-makers decide about service use based largely on
      the costs and perceived benefits of health interventions. Very often this leads
      to different decisions than those imagined by health planners, resulting in under
      utilisation of public services like immunisation. In the case of Lasbela district
      in the south of Pakistan, only one in every ten children is immunised despite
      free immunisation offers by government health services. METHODS/DESIGN: In 32
      communities representative of Lasbela district, 3344 households participated in a
      baseline survey on early child health. In the 18 randomly selected intervention
      communities, we will stimulate discussions on the household cost-benefit
      equation, as measured in the baseline. The reference (control) communities will
      also participate in the three annual follow-up surveys, feedback of the general
      survey results and the usual health promotion activities relating to
      immunisation, but without focussed discussion on the household cost-benefit
      equations. DISCUSSION: This project proposes knowledge translation as a two-way
      communication that can be augmented by local and international evidence. We will
      document cultural and contextual barriers to immunisation in the context of
      household cost-benefit equations. The project makes this information accessible
      to health managers, and reciprocally, makes information on immunisation effects
      and side effects available to communities. We will measure the impact of this two
      way knowledge translation on immunisation uptake.

PMID- 15985161
TI  - International public health research involving interpreters: a case study from
      Bangladesh.
AB  - BACKGROUND: Cross-cultural and international research are important components of
      public health research, but the challenges of language barriers and working with
      interpreters are often overlooked, particularly in the case of qualitative
      research. METHODS: A case-study approach was used to explore experiences of
      working with an interpreter in Bangladesh as part of a research project
      investigating women's experiences of emergency obstetric care. THE CASE STUDY:
      Data from the researcher's field notes provided evidence of experiences in
      working with an interpreter and show how the model of interviewing was adapted
      over time to give a more active role to the interpreter. The advantages of a more
      active role were increased rapport and "flow" in interviews. The disadvantages
      included reduced control from the researcher's perspective. Some tensions between
      the researcher and interpreter remained hard to overcome, irrespective of the
      model used. Independent transcription and translation of the interviews also
      raised questions around accuracy in translation. CONCLUSION: The issues examined
      in this case study have broader implications for public health research. Further
      work is needed in three areas: 1) developing effective relationships with
      interpreters; 2) the impact of the interpreter on the research process; and 3)
      the accuracy of the translation and level of analysis needed in any specific
      public health research. Finally, this paper highlights the importance to authors
      of reflecting on the potential impact of translation and interpretation on the
      research process when disseminating their research.

PMID- 15985162
TI  - Bioinformatics in microbial biotechnology--a mini review.
AB  - The revolutionary growth in the computation speed and memory storage capability
      has fueled a new era in the analysis of biological data. Hundreds of microbial
      genomes and many eukaryotic genomes including a cleaner draft of human genome
      have been sequenced raising the expectation of better control of microorganisms.
      The goals are as lofty as the development of rational drugs and antimicrobial
      agents, development of new enhanced bacterial strains for bioremediation and
      pollution control, development of better and easy to administer vaccines, the
      development of protein biomarkers for various bacterial diseases, and better
      understanding of host-bacteria interaction to prevent bacterial infections. In
      the last decade the development of many new bioinformatics techniques and
      integrated databases has facilitated the realization of these goals. Current
      research in bioinformatics can be classified into: (i) genomics--sequencing and
      comparative study of genomes to identify gene and genome functionality, (ii)
      proteomics--identification and characterization of protein related properties and
      reconstruction of metabolic and regulatory pathways, (iii) cell visualization and
      simulation to study and model cell behavior, and (iv) application to the
      development of drugs and anti-microbial agents. In this article, we will focus on
      the techniques and their limitations in genomics and proteomics. Bioinformatics
      research can be classified under three major approaches: (1) analysis based upon
      the available experimental wet-lab data, (2) the use of mathematical modeling to
      derive new information, and (3) an integrated approach that integrates search
      techniques with mathematical modeling. The major impact of bioinformatics
      research has been to automate the genome sequencing, automated development of
      integrated genomics and proteomics databases, automated genome comparisons to
      identify the genome function, automated derivation of metabolic pathways, gene
      expression analysis to derive regulatory pathways, the development of statistical
      techniques, clustering techniques and data mining techniques to derive protein
      protein and protein-DNA interactions, and modeling of 3D structure of proteins
      and 3D docking between proteins and biochemicals for rational drug design,
      difference analysis between pathogenic and non-pathogenic strains to identify
      candidate genes for vaccines and anti-microbial agents, and the whole genome
      comparison to understand the microbial evolution. The development of
      bioinformatics techniques has enhanced the pace of biological discovery by
      automated analysis of large number of microbial genomes. We are on the verge of
      using all this knowledge to understand cellular mechanisms at the systemic level.
      The developed bioinformatics techniques have potential to facilitate (i) the
      discovery of causes of diseases, (ii) vaccine and rational drug design, and (iii)
      improved cost effective agents for bioremediation by pruning out the dead ends.
      Despite the fast paced global effort, the current analysis is limited by the lack
      of available gene-functionality from the wet-lab data, the lack of computer
      algorithms to explore vast amount of data with unknown functionality, limited
      availability of protein-protein and protein-DNA interactions, and the lack of
      knowledge of temporal and transient behavior of genes and pathways.

PMID- 15985164
TI  - Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear
      production and tear stability and reduced immunopathology in rabbits with induced
      autoimmune dacryoadenitis.
AB  - BACKGROUND: The most common cause of ocular morbidity in developed countries is
      dry eye, many cases of which are due to lacrimal insufficiency. Dry eye affects
      approximately 10 million in the United States, most of whom are women. In the
      U.S. alone, an estimated 2 million Sjogren's syndrome patients have dysfunctional
      lacrimal glands and severe dry eye, and there is no satisfactory treatment. These
      patients would benefit if their lacrimal tissue function could be restored.
      METHODS: The effect of adenovirus-mediated transfer of tumor necrosis factor
      (TNF)-alpha inhibitor gene on induced autoimmune dacryoadenitis was evaluated in
      a rabbit model. Soluble transgene protein was detected in tears by ELISA for 7
      days following transduction. RESULTS: Two weeks after induction of disease with
      activated lymphocytes, tear production, as determined by Schirmer testing, was
      reduced by about 40%, while tear film stability, as measured by tear breakup time
      (BUT), declined by 43%. Adenovirus-mediated gene therapy using AdTNFRp55-Ig given
      2 weeks after disease induction, resulted in the return of tear production to
      normal levels by week 4. In the treated disease group, tear BUT improved
      significantly by week 4. Rose bengal scores, an indicator of corneal surface
      defects, increased after disease induction and declined after gene therapy. In
      the lacrimal gland, the CD4 to CD8 T cell ratio was 4:1 in the disease group
      compared to 1:2 in the treated group. Infiltration of T cells and CD18+ cells was
      reduced approximately 50% after gene therapy. CONCLUSION: We concluded that
      therapeutic levels of soluble TNF inhibitor were achieved in the lacrimal gland
      and on the corneal surface. Anti-inflammatory cytokine gene expression might
      offer a potential therapeutic modality for the treatment of autoimmune
      dacryoadenitis, once suitable vectors become available.

PMID- 15985165
TI  - Nepal's war on human rights: a summit higher than Everest.
AB  - Nepal has witnessed serious human rights violations including arbitrary arrests,
      detentions, "disappearances", extra judicial executions, abductions and torture
      carried out by both the Royal Nepalese Army and the Maoist rebels in the 10 years
      of the "peoples war". Women and children have borne the brunt of the conflict.
      Massive displacement has led to adverse social and psychological consequences.
      While the reasons for the conflict are mainly indigenous and rooted in the social
      and economic inequities, remedies for health inequities must come not only from
      the health sector but also from broad social policies and adopting a
      participatory and conflict-sensitive approach to development. Meanwhile the
      international community needs to use its leverage to urge both sides to accept a
      human rights accord and honor international human rights and humanitarian laws,
      while investigating allegations of abuse and prosecute those responsible.

PMID- 15985163
TI  - Cloning and characterization of cDNAs encoding putative CTCFs in the mosquitoes,
      Aedes aegypti and Anopheles gambiae.
AB  - BACKGROUND: One of the many ascribed functions of CCCTC-binding factor (CTCF) in
      vertebrates is insulation of genes via enhancer-blocking. Insulation allows genes
      to be shielded from "cross-talk" with neighboring regulatory elements. As such,
      endogenous insulator sequences would be valuable elements to enable stable
      transgene expression. Recently, CTCF joined Su(Hw), Zw5, BEAF32 and GAGA factor
      as a protein associated with insulator activity in the fruitfly, Drosophila
      melanogaster. To date, no known insulators have been described in mosquitoes.
      RESULTS: We have identified and characterized putative CTCF homologs in the
      medically-important mosquitoes, Aedes aegypti and Anopheles gambiae. These genes
      encode polypeptides with eleven C2H2 zinc fingers that show significant
      similarity to those of vertebrate CTCFs, despite at least 500 million years of
      divergence. The mosquito CTCFs are constitutively expressed and are upregulated
      in early embryos and in the ovaries of blood-fed females. We have uncovered
      significant bioinformatics evidence that CTCF is widespread, at least among
      Drosophila species. Finally, we show that the An. gambiae CTCF binds two known
      insulator sequences. CONCLUSION: Mosquito CTCFs are likely orthologous to the
      widely-characterized vertebrate CTCFs and potentially also serve an insulating
      function. As such, CTCF may provide a powerful tool for improving transgene
      expression in these mosquitoes through the identification of endogenous binding
      sites.

PMID- 15985166
TI  - Oral clefts with associated anomalies: findings in the Hungarian Congenital
      Abnormality Registry.
AB  - BACKGROUND: Over the years, great efforts have been made to record the frequency
      of orofacial clefts in different populations. However, very few studies were able
      to account for the etiological and phenotypic heterogeneity of these conditions.
      Thus, data of cases with syndromic orofacial clefts from large population-based
      studies are infrequent. METHODS: Clinically recognized and notified syndromes and
      associations including cleft lip with or without cleft palate and other
      congenital anomalies were selected from the Hungarian Congenital Abnormality
      Registry (HCAR) between 1973 and 1982 and prevalence rates were calculated.
      RESULTS: Of 3,110 cases reported as having orofacial clefts, 653 had multiple
      congenital abnormalities. Of these, 60 (9.2%) had a known etiology (monogenic: 25
      or 3.8%, chromosomal: 31 or 4.7%, teratogenic: 4 or 0.6%). Seventy-three subjects
      (11.2%) had schisis in addition to the oral cleft. Skeletal anomalies were the
      most common malformations among cases with cleft lip with/without cleft palate
      (CL/P) and cleft palate (CP). Disorders of the central nervous system and
      cardiovascular malformations were also frequently associated. CONCLUSION:
      Surveillance systems, such as the HCAR, provide useful information about
      prevalence rates of congenital anomalies in a population. However, in a field
      where new syndromes are being discovered and classifications regularly updated,
      these rates should only be accepted as provisional.

PMID- 15985167
TI  - A model of the ternary complex of interleukin-10 with its soluble receptors.
AB  - BACKGROUND: Interleukin-10 (IL-10) is a cytokine whose main biological function
      is to suppress the immune response by induction of a signal(s) leading to
      inhibition of synthesis of a number of cytokines and their cellular receptors.
      Signal transduction is initiated upon formation of a ternary complex of IL-10
      with two of its receptor chains, IL-10R1 and IL-10R2, expressed on the cell
      membrane. The affinity of IL-10R1 toward IL-10 is very high, which allowed
      determination of the crystal structure of IL-10 complexed with the
      extracellular/soluble domain of IL-10R1, while the affinity of IL-10R2 toward
      either IL-10 or IL-10/sIL-10R1 complex is quite low. This so far has prevented
      any attempts to obtain structural information about the ternary complex of IL-10
      with its receptor chains. RESULTS: Structures of the second soluble receptor
      chain of interleukin-10 (sIL-10R2) and the ternary complex of IL-10/sIL-10R1/sIL
      10R2 have been generated by homology modeling, which allowed us to identify
      residues involved in ligand-receptor and receptor-receptor interactions.
      CONCLUSION: The previously experimentally determined structure of the
      intermediate/binary complex IL-10/sIL-10R1 is the same in the ternary complex.
      There are two binding sites for the second receptor chain on the surface of the
      IL-10/sIL-10R1 complex, involving both IL-10 and sIL-10R1. Most of the
      interactions are hydrophilic in nature, although each interface includes two
      internal hydrophobic clusters. The distance between C-termini of the receptor
      chains is 25 A, which is common for known structures of ternary complexes of
      other cytokines. The structure is likely to represent the biologically active
      signaling complex of IL-10 with its receptor on the surface of the cell membrane.

PMID- 15985168
TI  - Alterations of tumor suppressor gene p16INK4a in pancreatic ductal carcinoma.
AB  - BACKGROUND: Cell cycle inhibitor and tumor suppressor gene p16/MTS-1 has been
      reported to be altered in a variety of human tumors. The purpose of the study was
      to evaluate primary pancreatic ductal adenocarcinomas for potentially
      inactivating p16 alterations. METHODS: We investigated the status of p16 gene by
      polymerase chain reaction (PCR), nonradioisotopic single strand conformation
      polymorphism (SSCP), DNA sequencing and hypermethylation analysis in 25 primary
      resected ductal adenocarcinomas. In addition, we investigated p16 protein
      expression in these cases by immunohistochemistry (IHC) using a monoclonal
      antibody clone (MS-887-PO). RESULTS: Out of the 25 samples analyzed and compared
      to normal pancreatic control tissues, the overall frequency of p16 alterations
      was 80% (20/25). Aberrant promoter methylation was the most common mechanism of
      gene inactivation present in 52% (13/25) cases, followed by coding sequence
      mutations in 16% (4/25) cases and presumably homozygous deletion in 12% (3/25)
      cases. These genetic alterations correlated well with p16 protein expression as
      complete loss of p16 protein was found in 18 of 25 tumors (72%). CONCLUSION:
      These findings confirm that loss of p16 function could be involved in pancreatic
      cancer and may explain at least in part the aggressive behaviour of this tumor
      type.

PMID- 15985169
TI  - Methacholine bronchial provocation measured by spirometry versus wheeze detection
      in preschool children.
AB  - BACKGROUND: Determination of PC20-FEV1 during Methacholine bronchial provocation
      test (MCT) is considered to be impossible in preschool children, as it requires
      repetitive spirometry sets. The aim of this study was to assess the feasibility
      of determining PC20-FEV1 in preschool age children and compares the results to
      the wheeze detection (PCW) method. METHODS: 55 preschool children (ages 2.8-6.4
      years) with recurrent respiratory symptoms were recruited. Baseline spirometry
      and MCT were performed according to ATS/ERS guidelines and the following
      parameters were determined at baseline and after each inhalation: spirometry
      indices, lung auscultation at tidal breathing, oxygen saturation, respiratory and
      heart rate. Comparison between PCW and PC20-FEV1 and clinical parameters at these
      end-points was done by paired Student's t-tests. RESULTS AND DISCUSSION: Thirty
      six of 55 children (65.4%) successfully performed spirometry-sets up to the point
      of PCW. PC20-FEV1 occurred at a mean concentration of 1.70+/-2.01 mg/ml while PCW
      occurred at a mean concentration of 4.37+/-3.40 mg/ml (p < 0.05). At PCW, all
      spirometry-parameters were markedly reduced: FVC by 41.3+/-16.4% (mean +/-SD);
      FEV1 by 44.7+/-14.5%; PEFR by 40.5+/-14.5 and FEF25-75 by 54.7+/-14.4% (P < 0.01
      for all parameters). This reduction was accompanied by de-saturation, hyperpnoea,
      tachycardia and a response to bronchodilators. CONCLUSION: Determination of PC20
      FEV1 by spirometry is feasible in many preschool children. PC20-FEV1 often
      appears at lower provocation dose than PCW. The lower dose may shorten the test
      and encourage participation. Significant decrease in spirometry indices at PCW
      suggests that PC20-FEV1 determination may be safer.

PMID- 15985170
TI  - Retinopathy of prematurity and risk factors: a prospective cohort study.
AB  - BACKGROUND: Increased survival of extremely low birth infants due to advances in
      antenatal and neonatal care has resulted in a population of infants at high risk
      of developing retinopathy of prematurity (ROP). Therapeutic interventions include
      the use of antenatal and postnatal steroids however, their effects on the
      severity of ROP is in dispute. In addition, it has not been investigated whether
      severe ROP is due to therapeutic interventions or due to the severity of illness.
      The aim of the present study was to assess the association between the incidence
      of severe retinopathy of prematurity (greater than stage 2 - International
      classification of ROP) and mechanical ventilation, oxygen therapy, gestational
      age, antenatal and postnatal steroids in extremely low birth weight infants.
      METHODS: Neonates admitted to the neonatal intensive care unit in Lansing,
      Michigan, during 1993-2000 were followed to determine factors influencing the
      development of severe retinopathy of prematurity. Ophthalmologic examinations
      were started at 6 weeks and followed until resolution. We used logistic
      regression to estimate the relative risk (odds ratio) associated with risk
      factors of ROP. RESULTS: Of the neonates with <or= 1500 g birth weight, admitted
      to the neonatal intensive care unit, 85% (616/725) survived. Severe retinopathy
      of prematurity was detected in 7.8% of 576 neonates who had eye examinations.
      Neonates of lower gestational age (<or= 25 weeks and 26-28 weeks) had an
      increased odds ratio of 8.49 and 3.19 for the development of severe retinopathy
      of prematurity, respectively, compared to those 29 weeks and older. Late
      postnatal steroid treatment starting after 3 weeks of life showed 2.9-fold
      increased odds ratio, in particular administration for two weeks and more (OR:
      4.09, 95% CI: 1.52-11.03). With increasing antenatal steroids courses the risk of
      severe retinopathy of prematurity decreased, however, it was not significant.
      Lower gestational age, dependence on ventilation, and use of postnatal steroids
      were intertwined. Simultaneous presence of these factors seems to indicate severe
      disease status. CONCLUSION: Prolonged and late postnatal steroids treatment in
      very low birth weight infants may pose an increased risk for the development of
      severe retinopathy of prematurity; however, use of postnatal steroids may also be
      a marker for severity of illness. Further studies need to focus on biologic
      markers in the pathogenesis of retinopathy of prematurity and to better
      understand the influence of therapies.

PMID- 15985171
TI  - Estimation of airway obstruction using oximeter plethysmograph waveform data.
AB  - BACKGROUND: Validated measures to assess the severity of airway obstruction in
      patients with obstructive airway disease are limited. Changes in the pulse
      oximeter plethysmograph waveform represent fluctuations in arterial flow.
      Analysis of these fluctuations might be useful clinically if they represent
      physiologic perturbations resulting from airway obstruction. We tested the
      hypothesis that the severity of airway obstruction could be estimated using
      plethysmograph waveform data. METHODS: Using a closed airway circuit with
      adjustable inspiratory and expiratory pressure relief valves, airway obstruction
      was induced in a prospective convenience sample of 31 healthy adult subjects.
      Maximal change in airway pressure at the mouthpiece was used as a surrogate
      measure of the degree of obstruction applied. Plethysmograph waveform data and
      mouthpiece airway pressure were acquired for 60 seconds at increasing levels of
      inspiratory and expiratory obstruction. At each level of applied obstruction,
      mean values for maximal change in waveform area under the curve and height as
      well as maximal change in mouth pressure were calculated for sequential 7.5
      second intervals. Correlations of these waveform variables with mouth pressure
      values were then performed to determine if the magnitude of changes in these
      variables indicates the severity of airway obstruction. RESULTS: There were
      significant relationships between maximal change in area under the curve (P <
      .0001) or height (P < 0.0001) and mouth pressure. CONCLUSION: The findings
      suggest that mathematic interpretation of plethysmograph waveform data may
      estimate the severity of airway obstruction and be of clinical utility in
      objective assessment of patients with obstructive airway diseases.

PMID- 15985172
TI  - Consumer access to health information on the internet: health policy
      implications.
AB  - BACKGROUND: Providers of health care usually have much better information about
      health and health care interventions than do consumers. The internet is an
      important and rapidly evolving source of global health-related information and
      could provide a means of correcting for asymmetric information. However, little
      is known about who accesses this information and how it is used in New Zealand.
      The aims of this research were to: determine the nature of the health information
      sought, how respondents use the information, how helpful they perceive the
      information to be, and the self-assessed value of such information. METHODS: The
      researchers conducted an anonymous five minute telephone and mall intercept
      survey of randomly selected Wellington residents who had searched for health
      related information on the internet. Investigators entered the data into an Excel
      spreadsheet and transferred it to SPSS for data cleaning, data exploration and
      statistical analysis. Search time costs were based on the opportunity cost of
      income foregone and respondents were asked to provide a money value for the
      information found. RESULTS: Eighty-three percent of respondents accessed the
      internet from home, and 87% conducted the search for themselves. Forty-five
      percent of people were looking for general health and nutrition information, 42%
      for data about a specific illness and 40% for a medicine. After finding the
      information, 58% discussed it with a family member/friend/workmate, 36% consulted
      a general practitioner, 33% changed their eating or drinking habits, and 13% did
      nothing. Respondents found the information very quick to find and useful. It took
      them on average 0.47 hours and cost $12 (opportunity cost of time) to find the
      information. The average value of the data found was $60 and the net benefit to
      the consumer was $48 ($60 - $12). CONCLUSION: The results of this research could
      assist providers of health information via the internet to tailor their websites
      to better suit users' needs. Given the high perceived value of internet health
      information (greater than the average general practitioner fee) and the fact that
      some of the information found may be unreliable or even unsafe a valuable public
      health policy initiative would be to provide an improved New Zealand health
      information website containing information on how to evaluate data sourced from
      the world-wide-web and links to a range of useful and trustworthy health
      information sites.

PMID- 15985173
TI  - The appearance of discretionary income: influence on the prevalence of under- and
      over-nutrition.
AB  - Undernutrition--protein energy malnutrition or specific nutrient deficiencies-
      has been an inherent characteristic of impoverished populations throughout the
      world. Over-nutrition, obesity and nutrition imbalance is a current concern among
      those with rising though still insufficient incomes. We review data to suggest
      that the prevalence of these forms of malnutrition in populations is highly
      influenced by the rate of appearance of discretionary income. In developed
      countries, discretionary (alternatively "disposable") income refers to funds
      available after obligate payments (rent, heat, and the cost of getting to work)
      and payment for necessities (food and clothing). For families living at or below
      poverty, the last dollar earned is spent on these obligations. Undernutrition is
      common. By contrast, likelihood for obesity or imbalance increases with rising
      income when that last dollar is earned without certainty that it is available for
      discretionary spending. In the United States, neither under- nor over-nutrition
      is likely when new income is free and clear of debt or obligation. This occurs at
      approximately three times the poverty level. While income poverty and food
      insecurity affect risk for malnutrition rather than outcome, nutrition education
      programs that address issues of income and food support increase likelihood for
      adherence to recommendations.

PMID- 15985174
TI  - FACT--a framework for the functional interpretation of high-throughput
      experiments.
AB  - BACKGROUND: Interpreting the results of high-throughput experiments, such as
      those obtained from DNA-microarrays, is an often time-consuming task due to the
      high number of data-points that need to be analyzed in parallel. It is usually a
      matter of extensive testing and unknown beforehand, which of the possible
      approaches for the functional analysis will be the most informative. RESULTS: To
      address this problem, we have developed the Flexible Annotation and Correlation
      Tool (FACT). FACT allows for detection of important patterns in large data sets
      by simplifying the integration of heterogeneous data sources and the subsequent
      application of different algorithms for statistical evaluation or visualization
      of the annotated data. The system is constantly extended to include additional
      annotation data and comparison methods. CONCLUSION: FACT serves as a highly
      flexible framework for the explorative analysis of large genomic and proteomic
      result sets. The program can be used online; open source code and supplementary
      information are available at http://www.factweb.de.

PMID- 15985175
TI  - Morphogenesis of the anterior segment in the zebrafish eye.
AB  - BACKGROUND: The ocular anterior segment is critical for focusing incoming light
      onto the neural retina and for regulating intraocular pressure. It is comprised
      of the cornea, lens, iris, ciliary body, and highly specialized tissue at the
      iridocorneal angle. During development, cells from diverse embryonic lineages
      interact to form the anterior segment. Abnormal migration, proliferation,
      differentiation, or survival of these cells contribute to diseases of the
      anterior segment such as corneal dystrophy, lens cataract, and glaucoma.
      Zebrafish represent a powerful model organism for investigating the genetics and
      cell biology of development and disease. To lay the foundation for genetic
      studies of anterior segment development, we have described the morphogenesis of
      this structure in zebrafish. RESULTS: As in other vertebrates, the zebrafish
      anterior segment derives from diverse origins including surface ectoderm,
      periocular mesenchyme, and neuroepithelium. Similarly, the relative timing of
      tissue differentiation in the anterior segment is also conserved with other
      vertebrates. However, several morphogenic features of the zebrafish anterior
      segment differ with those of higher vertebrates. These include lens delamination
      as opposed to invagination, lack of iris muscles and ciliary folds, and altered
      organization in the iridocorneal angle. In addition, substantial dorsal-ventral
      differences exist within the zebrafish anterior segment. CONCLUSION:
      Cumulatively, our anatomical findings provide a reference point to utilize
      zebrafish for genetic studies into the mechanisms of development and maintenance
      of the anterior segment.

PMID- 15985176
TI  - Expressed sequence tags (ESTs) and simple sequence repeat (SSR) markers from
      octoploid strawberry (Fragaria x ananassa).
AB  - BACKGROUND: Cultivated strawberry (Fragaria x ananassa) represents one of the
      most valued fruit crops in the United States. Despite its economic importance,
      the octoploid genome presents a formidable barrier to efficient study of genome
      structure and molecular mechanisms that underlie agriculturally-relevant traits.
      Many potentially fruitful research avenues, especially large-scale gene
      expression surveys and development of molecular genetic markers have been limited
      by a lack of sequence information in public databases. As a first step to remedy
      this discrepancy a cDNA library has been developed from salicylate-treated, whole
      plant tissues and over 1800 expressed sequence tags (EST's) have been sequenced
      and analyzed. RESULTS: A putative unigene set of 1304 sequences--133 contigs and
      1171 singlets--has been developed, and the transcripts have been functionally
      annotated. Homology searches indicate that 89.5% of sequences share significant
      similarity to known/putative proteins or Rosaceae ESTs. The ESTs have been
      functionally characterized and genes relevant to specific physiological processes
      of economic importance have been identified. A set of tools useful for SSR
      development and mapping is presented. CONCLUSION: Sequences derived from this
      effort may be used to speed gene discovery efforts in Fragaria and the Rosaceae
      in general and also open avenues of comparative mapping. This report represents a
      first step in expanding molecular-genetic analyses in strawberry and demonstrates
      how computational tools can be used to optimally mine a large body of useful
      information from a relatively small data set.

PMID- 15985177
TI  - Progression of kidney disease in type 2 diabetes - beyond blood pressure control:
      an observational study.
AB  - BACKGROUND: The risk factors for progression of chronic kidney disease (CKD) in
      type 2 diabetes mellitus (DM) have not been fully elucidated. Although
      uncontrolled blood pressure (BP) is known to be deleterious, other factors may
      become more important once BP is treated. METHODS: All patients seen in the
      outpatient clinics of our hospital between January 1993 and September 2002 with
      type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney
      disease was evaluated by rate of decline of glomerular filtration rate (GFR) as
      estimated from the simplified MDRD formula. Variables associated with progression
      in univariate analyses were examined by multivariate analysis to determine the
      factors independently associated with kidney disease progression. RESULTS: 343
      patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP,
      glycated hemoglobin, and serum cholesterol during the study period were 138/72
      mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1
      1.73 m2-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black
      race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure,
      glycated hemoglobin, or serum cholesterol, were independently associated with
      progression. CONCLUSION: In a cohort of diabetic patients with CKD in whom mean
      BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and
      proteinuria but not blood pressure were independently associated with progression
      of kidney disease. Further understanding of the relationship between these
      factors and kidney disease progression may lead to beneficial therapies in such
      patients.

PMID- 15985178
TI  - Full cyclic coordinate descent: solving the protein loop closure problem in
      Calpha space.
AB  - BACKGROUND: Various forms of the so-called loop closure problem are crucial to
      protein structure prediction methods. Given an N- and a C-terminal end, the
      problem consists of finding a suitable segment of a certain length that bridges
      the ends seamlessly. In homology modelling, the problem arises in predicting loop
      regions. In de novo protein structure prediction, the problem is encountered when
      implementing local moves for Markov Chain Monte Carlo simulations. Most loop
      closure algorithms keep the bond angles fixed or semi-fixed, and only vary the
      dihedral angles. This is appropriate for a full-atom protein backbone, since the
      bond angles can be considered as fixed, while the (phi, psi) dihedral angles are
      variable. However, many de novo structure prediction methods use protein models
      that only consist of Calpha atoms, or otherwise do not make use of all backbone
      atoms. These methods require a method that alters both bond and dihedral angles,
      since the pseudo bond angle between three consecutive Calpha atoms also varies
      considerably. RESULTS: Here we present a method that solves the loop closure
      problem for Calpha only protein models. We developed a variant of Cyclic
      Coordinate Descent (CCD), an inverse kinematics method from the field of
      robotics, which was recently applied to the loop closure problem. Since the
      method alters both bond and dihedral angles, which is equivalent to applying a
      full rotation matrix, we call our method Full CCD (FCDD). FCCD replaces CCD's
      vector-based optimization of a rotation around an axis with a singular value
      decomposition-based optimization of a general rotation matrix. The method is easy
      to implement and numerically stable. CONCLUSION: We tested the method's
      performance on sets of random protein Calpha segments between 5 and 30 amino
      acids long, and a number of loops of length 4, 8 and 12. FCCD is fast, has a high
      success rate and readily generates conformations close to those of real loops.
      The presence of constraints on the angles only has a small effect on the
      performance. A reference implementation of FCCD in Python is available as
      supplementary information.

PMID- 15985180
TI  - The BpTRU automatic blood pressure monitor compared to 24 hour ambulatory blood
      pressure monitoring in the assessment of blood pressure in patients with
      hypertension.
AB  - BACKGROUND: Increasing evidence suggests that ABPM more closely predicts target
      organ damage than does clinic measurement. Future guidelines may suggest ABPM as
      routine in the diagnosis and monitoring of hypertension. This would create
      difficulties as this test is expensive and often difficult to obtain. The purpose
      of this study is to determine the degree to which the BpTRU automatic blood
      pressure monitor predicts results on 24 hour ambulatory blood pressure monitoring
      (ABPM). METHODS: A quantitative analysis comparing blood pressure measured by the
      BpTRU device with the mean daytime blood pressure on 24 hour ABPM. The study was
      conducted by the Centre for Studies in Primary Care, Queen's University,
      Kingston, Ontario, Canada on adult primary care patients who are enrolled in two
      randomized controlled trials on hypertension. The main outcomes were the mean of
      the blood pressures measured at the three most recent office visits, the initial
      measurement on the BpTRU-100, the mean of the five measurements on the BpTRU
      monitor, and the daytime average on 24 hour ABPM. RESULTS: The group mean of the
      three charted clinic measured blood pressures (150.8 (SD10.26) / 82.9 (SD 8.44))
      was not statistically different from the group mean of the initial reading on
      BpTRU (150.0 (SD21.33) / 83.3 (SD12.00)). The group mean of the average of five
      BpTRU readings (140.0 (SD17.71) / 79.8 (SD 10.46)) was not statistically
      different from the 24 hour daytime mean on ABPM (141.5 (SD 13.25) / 79.7 (SD
      7.79)). Within patients, BpTRU average correlated significantly better with
      daytime ambulatory pressure than did clinic averages (BpTRU r = 0.571, clinic r =
      0.145). Based on assessment of sensitivity and specificity at different cut
      points, it is suggested that the initial treatment target using the BpTRU be set
      at <135/85 mmHG, but achievement of target should be confirmed using 24 hour
      ABPM. CONCLUSION: The BpTRU average better predicts ABPM than does the average of
      the blood pressures recorded on the patient chart from the three most recent
      visits. The BpTRU automatic clinic blood pressure monitor should be used as an
      adjunct to ABPM to effectively diagnose and monitor hypertension.

PMID- 15985179
TI  - Genes involved in Drosophila glutamate receptor expression and localization.
AB  - BACKGROUND: A clear picture of the mechanisms controlling glutamate receptor
      expression, localization, and stability remains elusive, possibly due to an
      incomplete understanding of the proteins involved. We screened transposon mutants
      generated by the ongoing Drosophila Gene Disruption Project in an effort to
      identify the different types of genes required for glutamate receptor cluster
      development. RESULTS: To enrich for non-silent insertions with severe disruptions
      in glutamate receptor clustering, we identified and focused on homozygous lethal
      mutants in a collection of 2185 BG and KG transposon mutants generated by the
      BDGP Gene Disruption Project. 202 lethal mutant lines were individually dissected
      to expose glutamatergic neuromuscular junctions, stained using antibodies that
      recognize neuronal membrane and the glutamate receptor subunit GluRIIA, and
      viewed using laser-scanning confocal microscopy. We identified 57 mutants with
      qualitative differences in GluRIIA expression and/or localization. 84% of mutants
      showed loss of receptors and/or clusters; 16% of mutants showed an increase in
      receptors. Insertion loci encode a variety of protein types, including
      cytoskeleton proteins and regulators, kinases, phosphatases, ubiquitin ligases,
      mucins, cell adhesion proteins, transporters, proteins controlling gene
      expression and protein translation, and proteins of unknown/novel function.
      Expression pattern analyses and complementation tests, however, suggest that any
      single mutant - even if a mutant gene is uniquely tagged - must be interpreted
      with caution until the mutation is validated genetically and phenotypically.
      CONCLUSION: Our study identified 57 transposon mutants with qualitative
      differences in glutamate receptor expression and localization. Despite transposon
      tagging of every insertion locus, extensive validation is needed before one can
      have confidence in the role of any individual gene. Alternatively, one can focus
      on the types of genes identified, rather than the identities of individual genes.
      This genomic approach, which circumvents many technical caveats in favor of a
      wider perspective, suggests that glutamate receptor cluster formation involves
      many cellular processes, including: 1) cell adhesion and signaling, 2) extensive
      and relatively specific regulation of gene expression and RNA, 3) the actin and
      microtubule cytoskeletons, and 4) many novel/unexplored processes, such as those
      involving mucin/polycystin-like proteins and proteins of unknown function.

PMID- 15985181
TI  - A dynamic neuro-fuzzy model providing bio-state estimation and prognosis
      prediction for wearable intelligent assistants.
AB  - BACKGROUND: Intelligent management of wearable applications in rehabilitation
      requires an understanding of the current context, which is constantly changing
      over the rehabilitation process because of changes in the person's status and
      environment. This paper presents a dynamic recurrent neuro-fuzzy system that
      implements expert-and evidence-based reasoning. It is intended to provide context
      awareness for wearable intelligent agents/assistants (WIAs). METHODS: The model
      structure includes the following types of signals: inputs, states, outputs and
      outcomes. Inputs are facts or events which have effects on patients'
      physiological and rehabilitative states; different classes of inputs (e.g.,
      facts, context, medication, therapy) have different nonlinear mappings to a fuzzy
      "effect." States are dimensionless linguistic fuzzy variables that change based
      on causal rules, as implemented by a fuzzy inference system (FIS). The FIS, with
      rules based on expertise and evidence, essentially defines the nonlinear state
      equations that are implemented by nuclei of dynamic neurons. Outputs, a function
      of weighing of states and effective inputs using conventional or fuzzy mapping,
      can perform actions, predict performance, or assist with decision-making.
      Outcomes are scalars to be extremized that are a function of outputs and states.
      RESULTS: The first example demonstrates setup and use for a large-scale stroke
      neurorehabilitation application (with 16 inputs, 12 states, 5 outputs and 3
      outcomes), showing how this modelling tool can successfully capture causal
      dynamic change in context-relevant states (e.g., impairments, pain) as a function
      of input event patterns (e.g., medications). The second example demonstrates use
      of scientific evidence to develop rule-based dynamic models, here for predicting
      changes in muscle strength with short-term fatigue and long-term strength
      training. CONCLUSION: A neuro-fuzzy modelling framework is developed for
      estimating rehabilitative change that can be applied in any field of
      rehabilitation if sufficient evidence and/or expert knowledge are available. It
      is intended to provide context-awareness of changing status through state
      estimation, which is critical information for WIA's to be effective.

PMID- 15985182
TI  - Actively replicating West Nile virus is resistant to cytoplasmic delivery of
      siRNA.
AB  - BACKGROUND: West Nile virus is an emerging human pathogen for which specific
      antiviral therapy has not been developed. Recent studies have suggested that RNA
      interference (RNAi) has therapeutic potential as a sequence specific inhibitor of
      viral infection. Here, we examine the ability of exogenous small interfering RNAs
      (siRNAs) to block the replication of West Nile virus in human cells. RESULTS: WNV
      replication and infection was greatly reduced when siRNA were introduced by
      cytoplasmic-targeted transfection prior to but not after the establishment of
      viral replication. WNV appeared to evade rather than actively block the RNAi
      machinery, as sequence-specific reduction in protein expression of a heterologous
      transgene was still observed in WNV-infected cells. However, sequence-specific
      decreases in WNV RNA were observed in cells undergoing active viral replication
      when siRNA was transfected by an alternate method, electroporation. CONCLUSION:
      Our results suggest that actively replicating WNV RNA may not be exposed to the
      cytoplasmic RNAi machinery. Thus, conventional lipid-based siRNA delivery systems
      may not be adequate for therapy against enveloped RNA viruses that replicate in
      specialized membrane compartments.

PMID- 15985183
TI  - Transmission dynamics of rabies virus in Thailand: implications for disease
      control.
AB  - BACKGROUND: In Thailand, rabies remains a neglected disease with authorities
      continuing to rely on human death statistics while ignoring the financial burden
      resulting from an enormous increase in post-exposure prophylaxis. Past attempts
      to conduct a mass dog vaccination and sterilization program have been limited to
      Bangkok city and have not been successful. We have used molecular epidemiology to
      define geographic localization of rabies virus phylogroups and their pattern of
      spread in Thailand. METHODS: We analyzed 239 nucleoprotein gene sequences from
      animal and human brain samples collected from all over Thailand between 1998 and
      2002. We then reconstructed a phylogenetic tree correlating these data with
      geographical information. RESULTS: All sequences formed a monophyletic tree of 2
      distinct phylogroups, TH1 and TH2. Three subgroups were identified in the TH1
      subgroup and were distributed in the middle region of the country. Eight
      subgroups of TH2 viruses were identified widely distributed throughout the
      country overlapping the TH1 territory. There was a correlation between human
      dependent transportation routes and the distribution of virus. CONCLUSION: Inter
      regional migration paths of the viruses might be correlated with translocation of
      dogs associated with humans. Interconnecting factors between human socioeconomic
      and population density might determine the transmission dynamics of virus in a
      rural-to-urban polarity. The presence of 2 or more rabies virus groups in a
      location might be indicative of a gene flow, reflecting a translocation of dogs
      within such region and adjacent areas. Different approaches may be required for
      rabies control based on the homo- or heterogeneity of the virus. Areas containing
      homogeneous virus populations should be targeted first. Control of dog movement
      associated with humans is essential.

PMID- 15985184
TI  - Chemically synthesized zinc finger molecules as nano-addressable probes for
      double-stranded DNAs.
AB  - Our experiments describe an alternative method of dsDNA recognition using zinc
      finger (ZF) molecules which bind DNA specifically and with high affinity. Our aim
      was to develop zinc finger probes which are able to bind to dsDNA molecules at
      predetermined sites. In our basic approach we used pairs of complementary
      oligonucleotides to form dsDNAs, containing one of the three SP1-transcription
      factor motifs as a zinc finger recognition site. Two zinc finger probes of the
      SP1 motif were chemically synthesized and modified with a Dy-633 fluorophore. The
      SP1 peptides were folded into functional zinc fingers using zinc chloride. The
      addressable dsDNAs were immobilized on optical fibres, and the kinetics and
      binding rates of the artificial zinc finger probes were measured by a
      fluorescence detecting device (photomultiplying tube). The two zinc fingers and
      their corresponding DNA recognition sites served as specific probes and controls
      for the matching site and vice versa. Our experiments showed that a variety of
      dsDNA-binding probes may be created by modification of the amino acid sequence of
      natural zinc finger proteins. Our findings offer an alternative approach of
      addressing dsDNA molecules, for example for use in a nanoarray device.

PMID- 15985185
TI  - Diagnostic utility of p16 immunocytochemistry for Trichomonas in urine cytology.
AB  - We present a case in which p16 immunocytochemistry helped establish the diagnosis
      of Trichomonas in urine from a male patient. Based on this finding, we recommend
      p16 immunocytochemistry as a diagnostic tool for unexpected patients or specimen
      types in which potential trichomonads are identified following routine cytologic
      evaluation.

PMID- 15985186
TI  - Reliability of upright posture measurements in primary school children.
AB  - BACKGROUND: Correct upright posture is considered to be a measure of good
      musculoskeletal health. Little is known about the usual variability of children's
      upright standing posture. The aim of this study was to assess differences between
      repeated measures of upright posture in a group of primary school children.
      METHODS: Sagittal plane photographs of usual, relaxed upright standing posture of
      38 boys and girls aged 5-12 years were taken twice within an hour. Reflective
      markers were placed over the canthus, tragus, C7 spinous process, greater
      trochanter and lateral malleolus. Digitising software was used to calculate the
      x,y plane coordinates, from which five postural angles were calculated (trunk,
      neck, gaze, head on neck, lower limb). Height, weight, motor control estimates
      (as measured by the Brace Tests) and presence of recent pain were recorded for
      each child, and the association between the first test measure of posture angles
      and these factors was assessed using linear regression and ANOVA models. Multiple
      ANOVA models were applied to analyse the effect of repeated testing, and
      significant predictors on the angles. RESULTS: Four of the five postural angles
      (trunk, neck, head on neck, lower limb) were significantly influenced by age. As
      age was strongly associated with height (r2 = 0.84) and moderately associated
      with weight and motor control (r2 = 0.67, 0.56 respectively), these developmental
      parameters may well explain the age effect on angles. There was no relationship
      between age and pain reported on either the testing day, or recently, and there
      was no gender influence on any angle. There was no significant effect of repeated
      testing on any angle (ICC>0.93). None of the hypothesized predictors were
      associated with differences in angles from repeated testing. CONCLUSION: This
      study outlined the variability of relaxed upright standing posture of children
      aged 5-12 years, when measured twice in an hour. Age influenced the size of the
      angles but not the variability. While the subject numbers in this study are
      small, the findings provide useful information on which further studies in
      posture and its development in pre-adolescent children can be based.

PMID- 15985187
TI  - Role of viral evolutionary rate in HIV-1 disease progression in a linked cohort.
AB  - BACKGROUND: The actual relationship between viral variability and HIV disease
      progression and/or non-progression can only be extrapolated through
      epidemiologically-linked HIV-infected cohorts. The rarity of such cohorts accents
      their existence as invaluable human models for a clear understanding of molecular
      factors that may contribute to the various rates of HIV disease. We present here
      a cohort of three patients with the source termed donor A--a non-progressor and
      two recipients called B and C. Both recipients gradually progressed to HIV
      disease and patient C has died of AIDS recently. By conducting 15 near full
      length genome (8.7 kb) analysis from longitudinally derived patient PBMC samples
      enabled us to investigate the extent of molecular factors, which govern HIV
      disease progression. RESULTS: Four time points were successfully amplified for
      patient A, 4 for patient B and 7 from patient C. Using phylogenetic analysis our
      data confirms the epidemiological-linkage and transmission of HIV-1 from a non
      progressor to two recipients. Following transmission the two recipients gradually
      progressed to AIDS and one died of AIDS. Viral divergence, selective pressures,
      recombination, and evolutionary rates of HIV-1 in each member of the cohort were
      investigated over time. Genetic recombination and selective pressure was evident
      in the entire cohort. However, there was a striking correlation between
      evolutionary rate and disease progression. CONCLUSION: Non-progressing
      individuals have the potential to transmit pathogenic variants, which in other
      host can lead to faster HIV disease progression. This was evident from our study
      and the accelerated disease progression in the recipient members of he cohort
      correlated with faster evolutionary rate of HIV-1, which is a unique aspect of
      this study.

PMID- 15985188
TI  - An evaluation of the costs, effectiveness and quality of renal replacement
      therapy provision in renal satellite units in England and Wales.
AB  - OBJECTIVES: To survey of the structure, processes and organisation of renal
      satellite units (RSUs) in England and Wales (Phase 1), and to compare the
      effectiveness, acceptability, accessibility and economic impact of chronic
      haemodialysis performed in RSUs compared to main renal units (MRUs) (Phase 2).
      DATA SOURCES: Phase 1: all renal satellite units in England and Wales. Phase 2:
      haemodialysis patients in a representative sample (based on geography, site,
      private--public ownership, medical input) of 12 RSUs and their MRUs. REVIEW
      METHODS: Phase 1 consisted of a questionnaire survey. Semi-structured interviews
      were held in a representative sample of 24 RSUs with the senior clinician, senior
      nurse and manager. Phase 2 consisted of a cross-sectional comparison of patients
      in these RSUs and patients in the parent MRUs deemed suitable for satellite care
      by senior staff. Clinical information was obtained from medical notes and unit
      computer systems. Generic and disease specific health-related quality of life
      (HRQoL) measures were used. Co-morbidity was assessed by the Wright/Khan Index,
      the Lister/Chandna score, the Modified Charlson Index, and the Karnofsky
      Performance Score. Statistical analyses compared RSU versus MRU patients and took
      account of the paired and clustered nature of the data. RESULTS: In Phase 1,
      responses were received from 74/80 (93%) of RSUs; 2600 patients were being
      treated in these RSUs. The interviews were generally positive about the impact of
      RSUs in terms of improved accessibility and a better environment for chronic
      haemodialysis (HD) patients, and in expanding renal replacement therapy patients
      (RRT) capacity. In Phase 2, some 82% of eligible patients took part, 394 patients
      in the 12 RSUs and 342 in the parent MRUs. The response rate was similar in both
      groups. There were no significant differences in clinical processes of care. Most
      clinical outcomes were similar, especially after pooled analysis, although a few
      parameters were statistically significantly different -- notably the proportion
      achieving Renal Association Standards for adequacy of dialysis as measured by the
      urea reduction ratio (URR) was higher in the RSU patients. Patient-specific
      quality of life did not differ except on the patient satisfaction questions from
      the KDQOL, which were scored higher by the RSU sample. Strength of preference for
      health status on and off dialysis was very similar between the groups, as were EQ
      5D utilities. Major adverse events were not common in the RSU patients, although
      there were many hypotensive episodes on HD, a proportion of which affected the
      duration of the HD session. Of the costs measured, the only difference that was
      statistically significant was for District Nurse visits. Of particular note was
      that despite the MRU group having a higher proportion of patients hospitalised,
      this did not translate into a statistically significant budgetary impact in terms
      of the total cost per patient of hospitalisations or mean cost per patient per
      hospitalisation. CONCLUSIONS: This study has shown that RSUs are an effective
      alternative to MRU HD for a wide spectrum of patients. They improve geographic
      access for more dispersed areas and reduce patients' travel time, and are
      generally more acceptable to patients on several criteria. There does not seem to
      be an adverse impact of care in the RSUs although comparative long-term
      prospective data are lacking. The evidence suggests that satellite development
      could be successfully expanded; not all MRUs have any satellites and many have
      only a few. No single RSU model can be recommended but key factors would include
      local geography, the likely catchment population and the type of patients to be
      treated. There is a need for more basic budgetary information linking activity
      and expenditure to be available and more transparent, to perform at least an
      insightful top-down costing of the two care settings. Other areas suggested for
      further research include: a comparison of adverse events occurring in MRUs and
      RSUs with longer duration and larger numbers to identify more severe events,
      along with the more research into the scope for preventing such events, and a
      study into the patients deemed ineligible for satellite care. International
      comparisons of satellite care would also be useful.

PMID- 15985189
TI  - Imatinib for the treatment of patients with unresectable and/or metastatic
      gastrointestinal stromal tumours: systematic review and economic evaluation.
AB  - OBJECTIVES: To assess the clinical and cost-effectiveness of imatinib in the
      treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal
      stromal tumours (GISTs), relative to current standard treatments. DATA SOURCES:
      Electronic databases. REVIEW METHODS: As there were no randomised trials that
      have directly compared imatinib with the current standard treatment in patients
      with advanced GIST, this review included non-randomised controlled studies,
      cohort studies, and case series that reported effectiveness results of treatment
      with imatinib and/or other interventions in patients with advanced GIST. The
      effectiveness assessment was based on the comparison of results from imatinib
      trials and results from studies of historical control patients. Economic
      evaluation was mainly based on an assessment and modification (when judged
      necessary) of a model submitted by Novartis. RESULTS: Evidence from published
      uncontrolled trials involving 187 patients, and from abstracts reporting similar
      uncontrolled trials involving 1700 patients, indicates that approximately 50% of
      imatinib-treated individuals with advanced GIST experience a dramatic clinical
      response in terms of at least a 50% reduction in tumour mass. At present,
      although useful data are accumulating, it is not possible to predict which
      patients may respond in this way. Fifteen studies where possible GIST patients
      had been treated with therapies other than imatinib or best supportive care were
      also identified. All imatinib-treated patients experienced adverse effects,
      although they were relatively mild. Overall, imatinib was reported to be well
      tolerated. The most common serious events included unspecified haemorrhage and
      neutropenia. Skin rash, oedema and periorbital oedema were the common adverse
      events observed. Patients on the highest dose regimen (1000 mg per day in one
      trial) may experience dose-limiting drug toxicity. A structured assessment was
      carried out of the Novartis economic evaluation of imatinib for unresectable
      and/or metastatic GIST. The model was clearly presented and well written, its
      structure and input data were transparent, and the level of simplification was
      reasonable in terms of the objectives and data availability. However, the
      original Novartis model overestimated the cost-effectiveness of imatinib because
      of disproportion of survival and time-to-treatment failure in the imatinib arm,
      and the use of a possibly biased survival curve for patients in the control arm.
      The original Novartis model was modified to correct these two important
      shortcomings, which made it less sensitive to the choice of the survival curve
      for the control patients. According to the modified Novartis model, the estimated
      cost per quality-adjusted life-year (QALY) was 85,224 UK pounds (range 51,515-
      98,889 UK pounds) after 2 years, 41,219 UK pounds (27,331--44,236 UK pounds)
      after 5 years and 29,789 UK pounds (21,404--33,976 UK pounds) after 10 years. The
      results from a new Birmingham model were also within the range of estimates from
      the modified Novartis model. CONCLUSIONS: Evidence from uncontrolled studies
      indicates that the treatment with imatinib brings about clinically significant
      shrinkage of tumour mass in about half of patients with unresectable and/or
      metastatic, KIT-positive GIST. Results of modelling based on data from
      uncontrolled studies suggest that imatinib treatment improves survival in
      patients with unresectable and/or metastatic GIST. The economic evaluation
      modelling suggests that the cost per QALY gained ranges from 51,515 to 98,889 UK
      pounds after 2 years, from 27,331 to 44,236 UK pounds after 5 years, and from
      21,404 to 33,976 UK pounds after 10 years. Further research is needed into
      quality of life within trials involving patients with advanced malignancy, and
      long-term follow-up of adverse events is needed. Subgroup analysis of which, if
      any, patient types have a better or worse response to imatinib is also required.
      Analysis of individual patient data may be a good way of exploring these issues.
      There are many uncertainties surrounding imatinib prescription, such as the
      length of time patients should be on imatinib, the dose, drug resistance and the
      optimum time-point in the disease course at which to give the drug. Secondary
      research such as an update of this systematic review and a reassessment of the
      model is highly recommended when ongoing trials reach completion.

PMID- 15985190
TI  - [Protein folding: the second translation of the genetic message].

PMID- 15985191
TI  - [A new role for insulin in the control of energetic metabolism in liver].

PMID- 15985192
TI  - [Post-transcriptional regulation of gene expression: another role for Staufen1].

PMID- 15985193
TI  - [Unpredictable and attentive human X chromosome].

PMID- 15985194
TI  - [Mystery upon the origin for the selection of AIDS-protective CCR5Delta32].

PMID- 15985195
TI  - [A new role for arginine methylation in DNA repair].

PMID- 15985196
TI  - [Drug-induced osteomalacia : possible role of PXR, a receptor involved in
      detoxification].

PMID- 15985197
TI  - [Polymorphism of kallikrein gene and abnormalities of the endothelial function].

PMID- 15985198
TI  - [Ins(1,4,5)P3: a messenger for hearing].

PMID- 15985199
TI  - [Serotonin in dopamine neurons? An interesting hypothesis about the mechanism of
      action of antidepressants with a feeling of << deja-vu >>...].

PMID- 15985200
TI  - [Antiapoptotic role of ferritin heavy chain].

PMID- 15985202
TI  - [Protein folding: in vitro studies].
AB  - Protein folding is a topic of fundamental interest since it concerns the
      mechanisms by which the genetic information is translated into the three
      dimensional and functional structure of proteins. In these post-genomic times,
      the knowledge of the fundamental principles is required in the exploitation of
      the information contained in the increasing number of sequenced genomes. Protein
      folding also has a practical application in the understanding of different
      pathologies associated with protein misfolding and aggregation. Significant
      advances have been made ranging from the Anfinsen postulate to the "new view"
      which describes the folding process in terms of an energy landscape. These
      insights arise from both theoretical and experimental studies. Unravelling the
      mechanisms of protein folding represents one of the most challenging problems to
      day. This is an extremely active field of research involving aspects of biology,
      chemistry, biochemistry, computer science and physics.

PMID- 15985203
TI  - [The << folding problem >>: can one predict the structure of proteins?].
AB  - A protein's three-dimensional structure is encoded in its amino acid sequence.
      The << folding problem >> consists in predicting one based on the other. This
      classic problem of molecular biology has seen important steps forward in recent
      years. The raw power of today's computers, along with the mobilization of
      thousands of internauts, have allowed several small proteins to be literally
      folded up in a computer, through simulations. Moreover, international programs
      for structural genomics aim to determine the experimental structures of hundreds
      of proteins in several organisms, and to model the others by homology to known
      structures. This will lead to a nearly-complete map of the protein structure
      universe, shedding light on the past evolution and current functions of today's
      proteins, and suggesting new targets for therapeutic strategies.

PMID- 15985204
TI  - [Recombinant protein folding and production].
AB  - The biotechnology of recombinant protein production is now entering its most
      advanced stage, and the growth of industrial protein pharmaceuticals provides
      solid proof of this evolution. However, the systematic conversion of genetic
      information into a biologically active protein is constantly confronted by the
      fundamental problem of protein folding in cells, and many recombinant proteins
      are not produced in their native state. Instead, they aggregate into a
      biologically inactive state. Although this aggregation reaction has some
      practical advantages, in vitro renaturation of recombinant proteins, after
      solubilization of cellular aggregates, is still an empiric and random process.
      Thus, it is better to control cellular expression conditions to minimize this
      problem inside the cells. The most attractive approach is certainly the
      development of high throughput genetic screens to monitor efficient protein
      folding.

PMID- 15985205
TI  - [Heat shock proteins as molecular chaperones].
AB  - Exposure to different conditions or agents that destabilize cell homeostasis
      often alters protein folding. Depending on stress intensity irreversible protein
      aggregation and cell death can occur. Cells have developed a conserved defense
      mechanism aimed at reducing the deleterious effects induced by protein folding
      alteration. This mechanism is characterized by the expression of a small number
      of genes encoding specific proteins, named Hsps. Several of these proteins act as
      molecular chaperones through their ability to refold polypeptides with an altered
      conformation. Moreover, constitutive Hsps homologues have been characterized that
      participate in the folding of newly made polypeptides, in the assembly of protein
      complexes in the endoplasmic reticulum, in the translocation of polypeptides
      through membranes or in masking mutations that alter protein folding.
      Neurodegeneratives and cancereous diseases are discussed as examples where high
      levels of Hsp expression can be either beneficial or deleterious to the cells.

PMID- 15985206
TI  - [Amyloidosis: a model of misfolded protein disorder].
AB  - Amyloidosis bears many characteristics of orphan diseases. Its diagnosis is
      difficult and often delayed. The main reasons thereof are its quite various
      clinical presentation: amyloidosis behaves as a new great masquerader, and the
      need to get a tissue sample to submit to specific dyes. Although we have been
      able for a long time to recognize amyloid, its intimate nature has remained quite
      completely enigmatic until recently. In fact, major advances in this way have
      appeared only in the last decade and it is now possible to consider the
      mechanisms of amyloidosis as a multistep phenomenon. Amyloidosis is no more
      thought only as a << storage disease >> of the extracellular space. This archaic
      viewpoint has shifted to the emerging paradigm of misfolded protein disorders.
      Amyloid proteins thus appear as a subgroup of misfolded proteins, where
      misfolding leads to subsequent aggregation. This aggregation may be a generic
      property of polypeptide chains possibly linked to their common peptide backbone
      that does not depend on specific amino acid sequences. And, in fact, many
      proteins can in vitro form amyloid-like aggregates, while in vivo, only 20
      amyloid proteins have been so far identified. Although misfolding and aggregation
      are quite well studied in vitro, the last step of amyloid deposition, i.e.
      anchorage to the extracellular matrix, can not be so easily approached.
      Proteoglycans and serum amyloid P component have nevertheless been identified as
      key elements involved in extracellular deposition of amyloid proteins. These
      advances have opened new avenues in the therapeutic of amyloid disorders. Current
      treatment consists of support or replacement of impaired organ function and
      measures to reduce the production of amyloidogenic precursor proteins. Potential
      novel therapeutic strategies include stabilisation of the native fold of
      precursor proteins with targeted small molecules, reversion of misfolded proteins
      to their native state with << beta-sheet breakers >>, inhibition of amyloid
      fibril propagation and enhancement of amyloid clearance either through
      immunotherapy or by reducing the stability of deposits through depletion of serum
      amyloid P component, and breaking the anchorage to the extracellular matrix with
      glycosaminoglycan analogs.

PMID- 15985207
TI  - [Prion proteins: folding and aggregation properties].
AB  - The partial unfolding or alternative folding of a class of polypeptides is at the
      origin of fascinating events in living cells. In their non-native conformation,
      these constitutive polypeptides called prions are at the origin of a protein
      based structural heredity. These polypeptides are closely associated to a class
      of fatal neurodegenerative illnesses in mammals and to the emergence and
      propagation of phenotypic traits in baker's yeasts. The structural transition
      from the correctly folded, native form of a prion protein to a persistent
      misfolded form that ultimately may cause cell death or the transmission of
      phenotypic traits is not yet fully understood. The mechanistic models accounting
      for this structure-based mode of inheritance and the extent of partial unfolding
      of prions or their alternative folding and the subsequent aggregation process are
      developed and discussed. Finally, the potential regulation of prion propagation
      by molecular chaperones is presented.

PMID- 15985208
TI  - [Semaphorins and cancers : an up 'dating'].
AB  - Semaphorins, first described as axon guidance molecules, play an essential role
      in neural development, angiogenesis and immunological response. In 1996, two
      semaphorin genes, SEMA3B and SEMA3F, were isolated from chromosomal region 3p21.3
      believed to contain a tumor suppressor gene based on frequent loss of
      heterozygosity in lung and breast cancer. Since these first studies, several
      semaphorins have been involved in tumor progression. Some semaphorins have been
      proposed to have pro-tumoral properties, whereas others have been shown to have
      tumor suppressive activity. This review summarizes the most recent data
      implicating semaphorins in cancers.

PMID- 15985209
TI  - [Facets of patient complaints: pain, suffering, and the importance of
      consideration].
AB  - Patient complaints, as it has often been recognized, serve to express multiple
      and varied experiences and needs. A number of options for filing complaints and a
      variety of ways for doing so have arisen recently, among which are ethics
      committees, support groups, palliative care units, and complaint examination
      committees. Today patients have many occasions for expressing their experiences,
      talking about distressing incidents, and making their needs known. Three orally
      related experiences are examined here, both from the viewpoint of the patient and
      in light of their cultural meanings: pain, suffering, and the importance of
      consideration. These are three expectations of care providers, but also three
      experiences that dispose patients to rethink their individuality and their
      relationships with others, to take stock of their pasts, and to reflect on who
      they are and who they want to become. The experience of illness has thus become
      pivotal in the process of constructing individual identity.

PMID- 15985210
TI  - [Dark cells: from morphology to function].

PMID- 15985211
TI  - [Dark cells: the endless story].

PMID- 15985212
TI  - [Opposition to Myriad Genetics patents and their total or partial revocation in
      Europe: early conclusions].
AB  - The proceedings instituted against three European patents held by the US company
      Myriad Genetics, on the BRCA1 gene and the breast cancer diagnosis gene, resulted
      in the total or partial revocation of these patents. These decisions put an end
      to the legal monopoly claimed by Myriad Genetics on the BRCA1 gene and on breast
      cancer gene tests, and left the field open to European geneticists to develop and
      implement their test methods within the framework of a clinical not-for-profit
      organization. The opposition procedure, through which any actor is allowed to
      challenge European patents, was used by geneticists doctors in Europe to refuse
      the emergence of an industrial monopoly on a medical service offered in a
      clinical context. The decision to revoke or strongly limit these patents was
      based on the European Patent Office's refusal to establish an invention priority
      on a sequence that had errors at the time the application was filed by the patent
      holder, in September 1994. The patent holder was granted an invention priority
      only on 24 March 1995, when it filed an application for a corrected sequence of
      the gene. But by then the BRCA1 gene sequence had already been divulged in a
      public data base, Genbank, from October 1994, notably by Myriad. Myriad Genetics'
      patents were thus victims of the patent race that prompted the firm to file
      multiple patent applications on insufficiently validated sequences, and of the
      conflict between diffusion in the public domain and the novelty requirement.
      Opposition to the patents, undertaken by a coalition of medical institutions,
      human genetic societies, two States, Holland and Austria, an environmental
      protection organization (Greenpeace), and the Swiss Labour Party, made it
      possible to preserve and develop the clinical economy of genetic tests in Europe.
      It resulted in amendments to intellectual property laws in France and thus
      extended the possibility of using compulsory licences for public health purposes
      to in vitro diagnosis.

PMID- 15985213
TI  - [Partnership between academic research and industry to study a new anti
      osteoporotic drug].
AB  - The activity of the osteoclast, the cell responsible for bone resorption, is
      subjected to different regulation factors. Amongst these, those issued from the
      matrix, particularly released minerals such as calcium, are determinants. We have
      shown that variations in calcium concentration in the medium regulates resorption
      activity and duration of the osteoclast lifespan. The development of a new
      therapeutic agent, strontium ranelate, has shown very interesting clinical
      effects reliant on the stimulation of bone formation activity by osteoblasts and
      modulation of bone resorption activity. From our knowledge regarding osteoclast
      physiology, in particular calcium signaling pathways, and the control of
      different osteoclast cellular models, a consequent collaboration was formed
      between our laboratory and Servier in order to elaborate on the effects of
      strontium ranelate on the osteoclast. In several years, this collaboration has
      been further enriched by other collaborators in order to better understand this
      mechanism. It has also been shown that strontium likely interacts with the
      calcium-sensing receptor and that the pathways of intracellular signaling
      pathways activated by calcium and strontium ranelate via this receptor are
      different. In fact, within the scope of this collaboration with Servier,
      exchanges with other academic laboratories were initiated and collaboration on
      numerous techniques became possible. Then, it has been possible to confirm the
      presence of the calcium-sensing receptor on the osteoclasts and to demonstrate
      its role in the molecular events associated with strontium ranelate's effects on
      the osteoclast.

PMID- 15985214
TI  - [A unique clonal JAK2 mutation leading to constitutive signalling causes
      polycythaemia vera].

PMID- 15985215
TI  - Midkine regulates pleiotrophin organ-specific gene expression: evidence for
      transcriptional regulation and functional redundancy within the
      pleiotrophin/midkine developmental gene family.
AB  - Midkine (MK) and the highly related cytokine pleiotrophin (PTN) constitute the
      PTN/MK developmental gene family. The Mk and Ptn genes are essential for normal
      development of the catecholamine and renin-angiotensin pathways and the synthesis
      of different collagens. It is not known whether the Ptn and Mk genes regulate
      each other or whether PTN and MK are functionally redundant in development. We
      have now compared the levels of expression of Ptn and Mk in genetically deficient
      Mk -/- and Ptn -/- mice and found highly significant increases in Ptn gene
      expression in spinal cord, dorsal root ganglia, eye, heart, aorta, bladder, and
      urethra, but not in brain, bone marrow, testis, and lung of Mk -/- mice compared
      with wild type mice; a remarkable approximately 230-fold increase in Ptn
      expression levels was found in heart of Mk -/- mice and highly significant but
      lesser increases were found in six other organs. Differences in levels of Mk gene
      expression in Ptn -/- mice could not be detected in any of the organs tested. The
      data demonstrate that MK regulates Ptn gene expression with a high degree of
      organ specificity, suggesting that Ptn gene expression follows Mk gene expression
      in development, that the increase in Ptn gene expression is compensatory for the
      absence of MK in Mk -/- mice, that PTN and MK share a high degree of functional
      redundancy, and that MK may be very important in the development of heart in
      mouse.

PMID- 15985216
TI  - Endostatin competes with bFGF for binding to heparin-like glycosaminoglycans.
AB  - Endostatin is a potent inhibitor of angiogenesis and tumor growth. Here, we used
      human endothelial cells from lung capillaries to investigate if endostatin
      competes with the proangiogenic growth factors, bFGF and VEGF, for binding to
      costimulatory heparan sulfate molecules. Endostatin inhibited 79% and 95% of the
      increase in proliferation induced by bFGF and VEGF165, respectively. The
      stimulatory effect of VEGF165 was not affected by the presence of exogenous
      heparin, while that of bFGF was further enhanced in the presence of up to 0.1
      microg/ml heparin. The heparin-binding protein protamine completely blocked bFGF
      stimulated proliferation, while it did not affect the response to VEGF165.
      Simultaneous addition of endostatin and protamine led to additive effects both in
      inhibition of proliferation and induction of apoptosis. Although bFGF was found
      to bind more strongly to heparin-Sepharose than endostatin, the latter, but not
      the former, displaced protamine from heparin in solution, which supports the
      notion that endostatin can compete with bFGF for binding to heparan sulfate in
      vivo. Taken as a whole, our results demonstrate that there is a direct connection
      between the dependence of endostatin activity on heparin-like glycosaminoglycans
      and its ability to antagonize bFGF.

PMID- 15985217
TI  - Mechanisms of ammonia-induced cell death in rat cortical neurons: roles of NMDA
      receptors and glutathione.
AB  - The occurrence, nature and prevention of ammonia-induced cell death were assayed
      in cultured primary cortical neurons from newborn rats. Treatment with 1-10 mM
      ammonium chloride for 24 or 48 h, dose-dependently decreased neuronal survival
      (MTT assay) and GSH/GSSG ratio in the cultures, whereas total GSH content was
      significantly reduced only with 10mM ammonia. Treatment with a glutathione
      synthesis inhibitor, buthionyl sulfoximine (BSO) (10 microM), decreased the GSH
      content and GSH/GSSG ratio to a degree similar to that of 10 mM ammonia, but it
      did not decrease cell survival in control cells. This indicates that glutathione
      depletion per se is not a cause of ammonia-induced neuronal death. However,
      ammonia-induced decrease of cell viability was attenuated by incubation with
      glutathione diethyl ester (GEE), which transiently increased the intracellular
      GSH level in both control and ammonia-treated cells. Neuronal survival in the
      presence of ammonia was partly improved by the NMDA receptor antagonists MK-801
      and APV. Morphological analysis revealed that ammonia treatment causes both
      apoptotic and non-apoptotic neuronal death, the former not being inhibited by MK
      801. Apoptosis was the dominant type of cell death at 10mM ammonia, as concluded
      both from morphologic examination and the absence of survival improvement in the
      presence of GABA+nipecotic acid or taurine, model anti-excitotoxic treatments of
      cortical neurons. The mechanism underlying apoptosis may include inhibition of a
      survival kinase, Akt, whose activatory phosphorylation at Ser473 is reduced in
      neurons treated with 10 mM, but not 1 mM ammonia.

PMID- 15985218
TI  - Molecular heterogeneity in Yersinia enterocolitica and 'Y. enterocolitica-like'
      species--Implications for epidemiology, typing and taxonomy.
AB  - Yersinia enterocolitica is an extremely heterogeneous species. Serotyping and
      biotyping have been used extensively, in the past, to study its heterogeneity and
      epidemiology. Application of methods like ribotyping, pulsed-field gel
      electrophoresis and a host of other genomic techniques have further revealed
      molecular heterogeneity in this species. Furthermore, these methods may be used
      effectively to supplement serotyping and biotyping schema for studying
      epidemiology of Y. enterocolitica. This is evident from the ability of some of
      these methods to subtype strains belonging to serogroups O:3, O:9 and O:8 - which
      are most commonly encountered in human Yersiniosis. Multilocus enzyme
      electrophoresis and nucleotide sequencing have reiterated the taxonomic
      relationships of this organism. However there is paucity of information about the
      molecular heterogeneity of 'Y. enterocolitica-like' species, which need to be
      addressed in the future. Also, newer techniques such as amplified fragment length
      polymorphism, VNTR-based typing and multilocus sequence typing should be applied
      to further understand epidemiology, population structure and evolutionary
      genetics of Y. enterocolitica and 'Y. enterocolitica-like' species.

PMID- 15985219
TI  - Identification of glyceraldehyde-3-phosphate dehydrogenase of epithelial cells as
      a second molecule that binds to Porphyromonas gingivalis fimbriae.
AB  - Binding of Porphyromonas gingivalis to the host cells is an essential step in the
      pathogenesis of periodontal disease. P. gingivalis binds to and invades
      epithelial cells, and fimbriae are thought to be involved in this process. In our
      earlier studies, two major epithelial cell components of 40 and 50 kDa were
      identified as potential fimbrial receptors. Sequencing of a cyanogen bromide
      digestion fragment of the 50-kDa component resulted in an internal sequence
      identical to keratin I molecules, and hence this cytokeratin represents one of
      the epithelial cell receptors for P. gingivalis fimbriae. In this study, the 40
      kDa component of KB cells was isolated and its amino-terminal sequence
      determined. The N-terminal amino sequence was found to be GKVKVGVNGF and showed
      perfect homology with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
      Furthermore, purified P. gingivalis fimbriae were found to bind to rabbit muscle
      GAPDH. Antibodies directed against internal peptide 49-68 and 69-90 of fimbrillin
      were shown to inhibit the binding of P. gingivalis and of fimbriae to epithelial
      cells. Antibodies against these peptides also inhibited the binding of fimbriae
      to GAPDH. Our results confirmed that the amino-terminal domain corresponding to
      amino residues 49-68 of the fimbrillin protein is the major GAPDH binding domain.
      These studies point to GAPDH as a major receptor for P. gingivalis major fimbriae
      and, as such, GAPDH likely plays a role in P. gingivalis adherence and
      colonization of the oral cavity, as well as triggering host cell processes
      involved in the pathogenesis of P. gingivalis infections.

PMID- 15985220
TI  - Combined detection of Chlamydia trachomatis-specific antibodies against the 10
      and 60-kDa heat shock proteins as a diagnostic tool for tubal factor infertility:
      Results from a case-control study in Cameroon.
AB  - A case-control study was conducted to determine the diagnostic value of Chlamydia
      trachomatis-associated anti-Chsp10 and/or anti-Chsp60 antibodies in the detection
      of secondary infertility. There were significant associations between C.
      trachomatis infection and infertility (p<0.01), and between C. trachomatis
      specific anti-Chsp10 or anti-Chsp60 antibodies and secondary infertility
      (p<0.001). A significant correlation was found between anti-Chsp10 and anti
      Chsp60 titers (p<0.01). The detection of either C. trachomatis-associated anti
      Chsp10 or anti-Chsp60 antibodies cumulatively allowed specific diagnosis of
      secondary infertility (57.4% sensitivity, 75.5% specificity).

PMID- 15985221
TI  - Transcriptional regulation of beta-defensin-2 by lipopolysaccharide in cultured
      human cervical carcinoma (HeLa) cells.
AB  - Human beta-defensin-2 (hBD-2) is an antimicrobial peptide with a broad spectrum
      of antimicrobial activity against bacteria, yeast and fungi. Here, we analyzed
      the transcriptional regulation of hBD-2 in cultured human cervical carcinoma
      (HeLa) cells with or without lipopolysaccharide (LPS). DNA from position -329 to 
      39 in the hBD-2 promoter region contained the consensus binding sites for
      transcription factors, one site for nuclear factor for IL-6 expression (NF-IL6)
      and two sites for nuclear factor-(kappa)B (NF-(kappa)B). Reporter gene assays for
      promoter activity revealed that the region had the highest level of
      responsiveness to LPS. Furthermore, mutations in both of the NF-(kappa)B binding
      sites caused a significant reduction of the responsiveness to LPS, whereas
      mutation in the NF-IL6 binding site resulted in an elevation of the basal
      promoter activity. Electrophoretic mobility shift assays demonstrated that LPS
      induced the binding of HeLa nuclear factors to 60-bp probe containing the two NF
      (kappa)B binding sites, suggesting that the sites were essential for the binding.
      Our results suggest that the two NF-(kappa)B binding sites contribute to LPS
      mediated hBD-2 transcription while the NF-IL6 binding site represses LPS
      independent hBD-2 transcription in the HeLa cells.

PMID- 15985222
TI  - Immunization with glutathione S-transferase and mutant toxic shock syndrome toxin
      1 fusion protein protects against Staphylococcus aureus infection.
AB  - To investigate whether immunization with glutathione S-transferase (GST) and
      mutant toxic shock syndrome toxin 1 (mTSST-1) fusion protein can protect against
      Staphylococcus aureus infection, we purified a non-toxic mutant GST-mTSST-1
      fusion protein. Mice were immunized with the GST-mTSST-1 plus alum adjuvant and
      then challenged with viable S. aureus. The results showed that the survival rate
      of GST-mTSST-1-immunized group was higher and the bacteria counts in the organs
      were significantly lower than those of the non-immunized mice. Immunization with
      GST-mTSST-1 induced strongly the production of TSST-1 specific antibodies,
      especially immunoglobulin G1 and immunoglobulin G2b. Furthermore, the serum
      samples from GST-mTSST-1-immunized mice also significantly inhibited interferon
      gamma and tumor necrosis factor-alpha production from murine spleen cells by TSST
      1. These results suggest that vaccination with GST-mTSST-1 provides protection
      against S. aureus infection and that the protection might be mediated by TSST-1
      neutralizing antibody.

PMID- 15985223
TI  - Antibodies against human muscle enolase recognize a 45-kDa bacterial cell wall
      outer membrane enolase-like protein.
AB  - Enolase, is a glycolytic enzyme ubiquitous in higher organisms, where it forms
      tissue specific dimers of isoforms, also found in the cytoplasm of fermentative
      bacteria. The aim of this work was to identify enolase-like proteins in the cell
      wall of some Gram-negative bacteria using antibodies against human beta-enolase,
      an isoenzyme specific to skeletal and heart muscles. Cell wall outer membrane
      protein (OMP) preparations were obtained from 9 strains of Enterobacteriaceae and
      one of Pseudomonas aeruginosa. Specific enzymatic enolase activity was detected
      in the supernatant fractions of cytosolic and inner membrane material, but not in
      purified OMP preparations. Rabbit polyclonal antibodies specific against human
      beta-enolase were prepared and purified using immobilized human beta-enolase in
      affinity chromatography. In SDS-polyacrylamide gel electrophoresis and
      immunoblotting assay of purified OMP preparations, rabbit anti-enolase antibody
      interacted specifically with a few OMPs, of which a 45-kDa band also interacted
      with human sera of patients presenting Buerger disease and atherosclerosis. The
      most distinct interaction of human sera was observed with a 45-kDa OMP of
      Klebsiella pneumoniae. This protein was further isolated from K. pneumoniae cell
      mass in two ways, namely preparative SDS-polyacrylamide gel electrophoresis and
      specific affinity chromatography using immobilized affinity-purified rabbit
      antibody raised against human beta-enolase. The data obtained from tandem mass
      spectrometry tryptic peptide analysis and sequence comparison of human and
      bacterial enolases using protein databases, could reveal the similarity in the
      epitopes between membrane enolase-like protein from Klebsiella and human beta
      enolase. The results show that the protein present in all studied strains has a
      common epitope on human beta-enolase. These data raise the question whether such
      a bacterial protein might be a marker for detecting and monitoring damage to
      skeletal and heart muscles.

PMID- 15985224
TI  - Phenotypic and genotypic discrepancy of Streptococcus pneumoniae strains isolated
      from Asian countries.
AB  - Non-typeable isolates of Streptococcus pneumoniae collected from Asian countries
      were characterized by optochin susceptibility test, bile solubility test,
      multilocus sequence typing of housekeeping genes, amplification of virulence
      related genes, 16S rDNA-RsaI digestion, and 16S rDNA sequencing. Six of 54 non
      typeable pneumococcal isolates showed divergence of gene sequences of recP and
      xpt from typical pneumococcal strains. Of these six atypical pneumococcal
      strains, two showed different results in optochin susceptibility or bile
      solubility test from typical pneumococcal strains. All six isolates showed high
      sequence dissimilarities of multilocus sequence typing, 16S rDNA sequences, and
      lytA sequences from typical S. pneumoniae strains. Data from this study suggest
      that classic tests such as optochin susceptibility and bile solubility tests may
      lead to incorrect identification of S. pneumoniae. These atypical strains may
      belong to different bacterial species from S. pneumoniae.

PMID- 15985225
TI  - In vitro inhibition of Helicobacter pylori by micromycetes.
AB  - The anti-Helicobacter pylori effect of 22 micromycetes were studied against one
      standard strain and 11 clinical isolates of H. pylori. Penicillium ochlochloron
      and Penicillium funiculosum have been proven the most active fungi against this
      microorganism. Further bio-guided chemical analysis of P. funiculosum afforded an
      active component identified as (-) 2,3,4-trihydroxybutanamide.

PMID- 15985226
TI  - Identification and characterization of the TonB region and its role in
      transferrin-mediated iron acquisition in Haemophilus parasuis.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease, which is
      responsible for considerable economic losses in the pig-rearing industry. The aim
      of the study reported here was the identification, sequencing and molecular
      characterization of the TonB region that includes tonB, exbBD, and tbpBA genes in
      H. parasuis. In addition, two fusion proteins were generated. One of them (pGEX
      6P-1-GST-TbpB) contained the first 501 amino acids of H. parasuis TbpB protein,
      while the second (pBAD-Thio-TbpB-V5-His) included the first 102 amino acids of H.
      parasuis TbpB N-terminus domain. A panel of 14 hybridomas secreting monoclonal
      antibodies was raised against the two recombinant TbpB fusion proteins.
      Furthermore, to assess whether the expression of the H. parasuis ExbB, TbpB, and
      TbpA proteins was upregulated under conditions of restricted availability of
      iron, a rabbit polyclonal antibody against H. parasuis TbpB-His fusion protein
      was produced. A rabbit polyclonal antibody against serotype 7 of Actinobacillus
      pleuropneumoniae ExbB and TbpA proteins was also used for the detection of the
      homologous proteins in H. parasuis. Overall, the data indicate that H. parasuis,
      like other members of the Pasteurellaceae family, possesses the genetic elements
      of the TonB region for iron acquisition and the transferrin-binding proteins
      encoded under this region are upregulated under restricted iron availability.

PMID- 15985227
TI  - Comparative evaluation of intranasal and subcutaneous route of immunization for
      development of mucosal vaccine against experimental tuberculosis.
AB  - Activation of mucosal immunity in the respiratory tract is crucial for protection
      against respiratory infections. Whether the intranasal route of vaccination
      imparts better protection against pulmonary tuberculosis than that of
      subcutaneous vaccination remains a debatable issue. In this study, we have
      investigated the effect of the routes of immunization on the induction of
      immunoprotection against experimental tuberculosis employing mycobacterial
      culture filtrate proteins complexed with dimethyldioctadecylammonium bromide.
      Vaccination via intranasal and subcutaneous routes triggered immune activation in
      the spleen and cervical lymph node, while the former route of vaccination lead to
      higher antigen-specific lymphocyte proliferation, interferon-gamma, interleukin
      12 and interleukin-4 responses in cervical lymph node and induction of antigen
      specific IgA responses at mucosal level of the respiratory tract. Mice vaccinated
      via the intranasal route were found to be better protected against experimental
      tuberculosis particularly in lung compared to subcutaneous-immunized mice. These
      results emphasize the importance of the intranasal route vaccination in
      tuberculosis.

PMID- 15985228
TI  - Th2-type immune response observed in healthy individuals to sonicate antigen
      prepared from the most prevalent Mycobacterium tuberculosis strain with single
      copy of IS6110.
AB  - Different Mycobacterium tuberculosis strains operate different immune evasion
      strategies for their survival in the host. This mainly depends on the virulence
      of the strain and the host immune responses. The most virulent strains are
      actively involved in the transmission, widely spread in the community and induce
      differential immune responses. We evaluated the immune response of a sonicate
      antigen prepared from one predominant strain (S7) from M. tuberculosis harbouring
      a single copy of IS6110. Significant lymphoproliferative response against
      purified protein derivative from tubercle bacillus (PPD) and H37Rv antigens was
      observed in PPD positive normal individuals and tuberculosis patients. Interferon
      gamma (IFN-gamma) levels against these antigens were significantly increased in
      normal individuals but not in tuberculosis patients. The antigen S7 showed
      marginal T-cell proliferation but did not induce IFN-gamma secretion in both
      groups. Conversely, it induced significantly high levels of cytokine interleukin
      4 (IL-4) in normal individuals. The macrophage cytokines, IL-12 and tumour
      necrosis factor alpha (TNF-alpha), did not show S7 antigen specific stimulation.
      The intracellular cytokine further confirmed an increase in IL-4(+)/CD4+ T-cells
      and a decrease in IFN-gamma(+)/CD4+ T-cells upon stimulation. The antibody
      response showed an increase in IgG and IgA levels against this antigen in normal
      individuals. These observations suggest that antigen S7 modulates the immune
      response towards T helper cell type 2 by suppressing T helper cell type 1
      protective immune response in PPD positive normal individuals. We speculate that
      some components of this sonicate antigen are associated with immunosuppressive
      response.

PMID- 15985230
TI  - Pharmacologic preconditioning effects: prostaglandin E1 induces heat-shock
      proteins immediately after ischemia/reperfusion of the mouse liver.
AB  - Prostaglandin E1 (PGE1) has several potential therapeutic effects, including
      cytoprotection, vasodilation, and inhibition of platelet aggregation. This study
      investigates the protective action of PGE1 against hepatic ischemia/reperfusion
      injury in vivo using a complementary DNA microarray. PGE1 or saline was
      continuously administered intravenously to mice in which the left lobe of the
      liver was made ischemic for 30 minutes and then reperfused. Livers were harvested
      0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the
      samples were labeled with two different fluorescent dyes and hybridized to the
      RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays.
      Serum alanine aminotransferase and aspartate aminotransferase levels at 180
      minutes postreperfusion were significantly lower in the PGE1-treated group than
      in the saline-treated group. The cDNA microarray analysis revealed that the genes
      encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and
      glutathione S-transferase were upregulated at the end of the ischemic period (0
      minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1
      induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an
      important role in the protective effects of PGE1 against ischemia/reperfusion
      injury of the liver.

PMID- 15985231
TI  - Intraperitoneal treatment with dimethylthioampal (DIMATE) combined with surgical
      debulking is effective for experimental peritoneal carcinomatosis in a rat model.
AB  - The goal was to evaluate the efficiency of intraperitoneal administration of
      dimethylthioampal (DIMATE), a cellular apoptosis inducer, combined, or not, with
      cytoreductive surgery on rats with peritoneal adenocarcinomatosis. Peritoneal
      carcinomatosis was induced in rats by intraperitoneal injection of adenocarcinoma
      cell line DHD/K12/pro B. Intraperitoneal DIMATE was given at 17.3 mg/kg. Rats
      were randomized into five groups of eight animals, regarding the day of treatment
      (2 days or 20 days after peritoneal carcinomatosis induction) and the combination
      with cytoreductive surgery. All rats were killed at 30 days to evaluate
      carcinomatosis extent (quantitative score) and ascites volume. The quantitative
      score of carcinomatosis and the ascites volume were significantly reduced in the
      groups treated with DIMATE at day 2 (P = 0.005 and P < 0.001, respectively) and
      when DIMATE was used with cytoreductive surgery at day 20 (P = 0.009 and P <
      0.001, respectively). Cytoreductive surgery or DIMATE used alone at day 20 had no
      significant influence. The intraperitoneal DIMATE administration at day 20, when
      not combined with surgery, had no significant influence on carcinomatosis extent
      or on ascites volume. Intraperitoneal DIMATE appeared to be an efficient drug in
      the prevention or treatment of peritoneal carcinomatosis when combined with
      cytoreductive surgery or when it was given by intraperitoneal route, before the
      development of macroscopic peritoneal carcinomatosis. It appears to be a
      promising therapeutic agent to be investigated in a human phase I trial in
      peritoneal carcinomatosis.

PMID- 15985232
TI  - Hand-sewn coloanal anastomosis for distal rectal cancer: long-term clinical
      outcomes.
AB  - As the oncologic safety of coloanal anastomosis (CAA) has been proved by many
      other authors, the incidence of CAA following ultralow anterior resection has
      increased. The purpose of this study is to evaluate the functional outcome and
      complications of patients who underwent ultralow anterior resection and CAA for
      distal rectal cancer. Fifty-seven patients underwent CAA following ultralow
      anterior resection between July 1997 and November 2003. Forty-four patients, who
      were followed up more than 6 months after diverting ileostomy closure, were
      evaluated for recurrence, complications, and functional outcomes. The mean follow
      up period was 36.3 +/- 22.8 months (range, 8-83 months). The complications were
      multiple fistula (n = 3), fistula with anal stenosis (n=1), local recurrence with
      anal stenosis (n = 1), and anal stenosis (n = 7). Anal incontinence (Kirwan grade
      III) was noted in 14 patients, and bowel movements were observed more than six
      times per day in 16 patients. Overall recurrence occurred in six patients
      (13.6%). The 5-year survival rate was 85.3%, and the disease-free 5-year survival
      rate was 73.3%. Although CAA in patients with rectal cancer provides excellent
      long-term survival, a low risk of recurrence, and tolerable function,
      complications and poor functional outcomes of CAA do occur. Therefore, the choice
      of this method should be considered carefully.

PMID- 15985233
TI  - Surgical outcome of para-aortic lymph node dissection preserving neural tissue
      based on anatomical evaluations.
AB  - The anatomical distribution of the para-aortic lymph nodes was studied to
      establish an effective operative procedure that preserves neural tissue for
      patients with advanced gastric cancer. Para-aortic lesions were anatomically
      examined in 31 cadavers, and histologic preparations of 14 cadavers were used to
      evaluate the relationship between para-aortic lymph nodes and surrounding neural
      tissue. Surgical results were analyzed in patients with D3 gastrectomy based on
      anatomical findings (n = 33). Anatomically, the splanchnic nerves merged into the
      celiac ganglion, which consisted of either one ganglion (type I) or several
      ganglia (type II). The average number of lymph nodes were 17.4 in the area
      superior to the superior mesenteric artery (SMA) and 13.3 in the area inferior to
      the SMA. According to the number of metastatic lymph nodes (< or = 3, > or = 4),
      the median survival time was 14.7 and 9.7 months, respectively (P < 0.02).
      Patients either with or without metastatic lymph nodes behind the neural tissue
      had a median survival time of 14.7 and 9.7 months, respectively (P < 0.02). We
      conclude that para-aortic lymph node dissection preserving neural tissue is
      useful in patients with three or fewer para-aortic metastatic lymph nodes that
      are in front of the neural tissue.

PMID- 15985234
TI  - Tissue-engineered patch for the reconstruction of inferior vena cava during
      living-donor liver transplantation.
AB  - In living-donor liver transplantation, only a portion of the donor's liver is
      grafted into the recipient; therefore, if the hepatic vein and inferior vena cava
      (IVC) in the recipient fail to be transformed or dilated properly, it could cause
      inadequate blood flow from the liver graft to the IVC. We have developed an easy
      to-use tissue engineered patch that can be used for the reconstruction of the
      hepatic vein and IVC. Five hybrid pigs (weighing 15-30 kg) served as the
      recipients of the patch. A bioabsorbable polymer sheet was used to produce the
      patch, with no cells seeded. The pigs were laparotomized, followed by the removal
      of a 3 x 2-cm portion of the infrahepatic IVC, which was then patched with the
      polymer sheet. Three months after the operation, the graft site was removed and
      subjected to gross and histologic examinations. All five pigs survived until they
      were killed 3 months after the operation. On gross examination, the polymer sheet
      grafted onto the IVC was completely absorbed, and the graft site was
      morphologically similar to the native IVC. In all five pigs, the patched IVC was
      free of stenosis or deformation. Immunohistochemical examination revealed that
      the patch site was lined with endothelial cells and that smooth muscle was
      present under the epithelium. Like the native IVC, the patch site tested positive
      for factor VIII. These findings suggest that this polymer sheet may be useful for
      the reconstruction of the IVC and hepatic vein during living-donor liver
      transplantation in humans.

PMID- 15985235
TI  - Laparoscopic subtotal colectomy for colonic inertia.
AB  - Colonic inertia is an uncommon condition, usually occurring in women in the third
      decade of life. Severity of symptoms may lead some patients to a surgical
      consultation. This is a retrospective review of 14 patients who underwent
      laparoscopic subtotal colectomy for colonic inertia, performed by a single
      surgeon from August 1993 to November 2002. The mean age of the patients was 38.5
      years (range 26-50 years); 93% of the patients were women. The common presenting
      symptoms included abdominal pain (93%), bloating (100%), constipation (100%), and
      nausea (57%). Median duration of symptoms before surgery was 4.5 years (range 1
      30 years). Subtotal colectomy was completed laparoscopically in 13 patients.
      There was one conversion (7%) because of adhesions. Eleven patients (78.6%) had
      undergone previous abdominal surgery. The mean operating room time was 153
      minutes (range 113-210 minutes). The median time to full bowel action was 2 days.
      One patient developed postoperative small bowel obstruction that required open
      exploration. Complete follow-up was available for 11 patients at a median follow
      up of 18 months (range 2-96 months). Ninety-one percent of the patients reported
      excellent satisfaction with surgery, and their bowel movement frequency changed
      from 1.2 (+/-0.2) per week preoperatives to 17.2 (+/-2.9) per week
      postoperatively (P < 0.001). Three patients (27%) continued to report abdominal
      pain and 3 patients (27%) continued to require laxatives postoperatively.
      Laparoscopic subtotal colectomy provides excellent symptom relief in patients
      with colonic inertia who do not respond to medical measures.

PMID- 15985236
TI  - Resection of mesenteric inflammatory veno-occlusive disease causing ischemic
      colitis.
AB  - Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of
      mesenteric ischemia that is diagnosed by histologic examination of the operative
      specimen. Recurrence of symptoms occurs, but further resection of ischemic
      intestine is seldom required. We describe the case of MIVOD in a young patient
      with clinical findings of ischemic colitis. The patient experienced complete
      resolution of the process, thus confirming the relatively benign course of this
      disease following resection. This report substantiates resolution of the
      inflammatory process after resection, colostomy, and reanastomosis. We review the
      literature and make conclusions regarding the clinical management of this
      disease.

PMID- 15985237
TI  - Gallbladder carcinosarcoma: a case report and literature review.
AB  - Carcinosarcoma of the gallbladder is a rare malignancy characterized by both
      malignant epithelial and mesenchymal components. The clinical behavior of this
      tumor is extremely aggressive. Only 26 cases have been reported in the world
      literature to date. We report the case of a 64-year-old woman who had fever
      associated with a right upper quadrant mass. An exploratory laparotomy through a
      right upper quadrant incision was performed at another institution, and the
      patient was thought to have severe acute cholecystitis that would require
      additional antibiotic therapy before attempted resection. She was referred to our
      center, where abdominal CT showed a 6.4 x 8.2 cm pericholecystic mass involving
      the hepatic flexure of the colon. The patient underwent cholecystectomy and
      hepatic wedge resection, pancreaticoduodenectomy, and right hemicolectomy.
      Pathologic examination of the surgical specimen revealed two histologic
      components consisting of squamous cell carcinoma and spindle cell sarcoma of
      gallbladder origin, consistent with carcinosarcoma. All seven lymph nodes in the
      pancreaticoduodenectomy specimen were negative for tumor. We present this case
      and a review of the literature and current treatment recommendations.

PMID- 15985238
TI  - Epithelioid angiosarcoma of the gallbladder: case report.
AB  - A patient with epithelioid angiosarcoma of the gallbladder is described. This is
      only the second case of an extremely rare but highly aggressive tumor reported in
      the international literature. Pathophysiological, clinical, and therapeutic
      aspects are discussed in relation to the available data on angiosarcomas of the
      gallbladder.

PMID- 15985239
TI  - Pain persists in many patients five years after removal of the gallbladder:
      observations from two randomized controlled trials of symptomatic, noncomplicated
      gallstone disease and acute cholecystitis.
AB  - After removal of the gallbladder, pain may persist in some patients. To study
      this condition, 124 patients from two randomized trials, including those with
      symptomatic noncomplicated gallbladder stones (n = 90) and acute cholecystitis (n
      = 34), were interviewed, while 139 patients (90%) excluded from both trials
      responded to a questionnaire 5 years after the operation. Thirty-four patients
      (27%) of those randomized had pain; 23 (18%) had diffuse, steady pain; and 11
      (9%) had pain attacks resembling their preoperative symptoms. A significant
      dominance of diffuse pain occurred in women (P = 0.024), especially those younger
      than 60 years (P = 0.004). A tendency for the diffuse type to be dominant was
      also present in the group of female patients with symptomatic noncomplicated
      gallbladder stones (P = 0.052). Of the excluded patients, 18% (25/139) had pain,
      but 88% of them (96% of the men and 87% of the women) were satisfied with the
      result of the operation. The overall number of patients with postoperative pain
      was 22% (59/263). We conclude that persisting abdominal pain 5 years after the
      operation was mainly of a nonspecific type, found mostly in younger women who had
      had noncomplicated gallstone disease. Eighty-eight percent of the excluded
      patients declared themselves satisfied with the result of cholecystectomy.

PMID- 15985240
TI  - Novel bile duct repair for bleeding biliary anastomotic varices: case report and
      literature review.
AB  - An unusual case of variceal bleeding at the site of a biliary enteric anastomosis
      is presented. This entity can occur when a high-to-low pressure gradient forms in
      a variceal field. In this case the anastomotic site was the location of the
      pressure gradient from the high-pressure small bowel varices to the low-pressure
      biliary tract. This was successfully treated by disconnection of the anastomosis.
      The resulting biliary defect was patched with small intestinal submucosa, which
      functioned successfully as a scaffold for biliary epithelial ingrowth.

PMID- 15985241
TI  - The unsolved problem of fistula after left pancreatectomy: the benefit of
      cautious drain management.
AB  - The aim of the study was to identify factors related to the onset of pancreatic
      fistula and to define the characteristics of the fistula. The study group was
      composed of 123 patients who underwent left pancreatectomy since 1996. Pancreatic
      closure was accomplished by a hand-sewn technique (39 patients) or two kinds of
      mechanical staplers: Proximate (Ethicon Endo-Surgery, Cincinnati, OH) (46
      patients) and Endo-GIA (United States Surgical, Norwalk, CT) (38 patients).
      Fistula was defined as output greater than 5 ml, with amylase x 5, after day 5.
      In case of fistula, the drain removal was scheduled at a daily output less than 5
      ml. Mortality was 0%, morbidity was 48%, and pancreatic fistula rate was 34%.
      Fistula rate was 38% after hand-sewn closure, 26% after Proximate, and 39% after
      Endo-GIA (NS). None of the other factors (separate duct ligation, hand-sewn
      suture in addition to stapler, spleen preservation, use of pledgetted suture,
      sex, age, and indication for pancreatectomy) proved to be related to a reduction
      in the onset of fistula. All fistulas healed spontaneously. Mean fistula duration
      was 36 days; 92.8% of patients with fistula were discharged with drain. The
      policy of delayed drain removal allowed a low rate of fistula associated
      morbidity (16%) and of readmission (4.7%). In conclusion, fistula is an unsolved
      problem of left pancreatectomy. However, a careful drain management allows a good
      outcome in patients with fistula.

PMID- 15985242
TI  - Intraductal papillary mucinous tumor of the pancreas associated with autosomal
      dominant polycystic kidney disease.
AB  - A 43-year-old male with a history of autosomal dominant polycystic kidney disease
      (ADPKD) was admitted to our center with severe abdominal pain and was diagnosed
      with acute pancreatitis. CT showed multiple cysts in the liver and both kidneys
      along with ADPKD and a cystic mass, 4 cm in diameter, in the pancreatic head. The
      main pancreatic duct was dilated to 1 cm in diameter. The patient was diagnosed
      with acute pancreatitis due to intraductal papillary mucinous tumor (IPMT), and
      pancreatoduodenectomy was performed. Histologic examination revealed a
      multiloculated cystic tumor filled with mucin in the head of the pancreas.
      Microscopically, the tumor was diagnosed as adenocarcinoma and was found to have
      invaded the main pancreatic duct. Although, in addition to our case, only seven
      cases with association between ADPKD and malignant neoplasms have been reported,
      five of these cases had neoplasms arising from the pancreas. Therefore, we
      suggest that some genetic interactions may exist between ADPKD and pancreatic
      carcinogenesis.

PMID- 15985243
TI  - Preservation of the left gastric vein in delayed gastric emptying after pylorus
      preserving pancreaticoduodenectomy.
AB  - The definition of delayed gastric emptying (DGE) after pyloric-preserving
      pancreaticoduodenectomy (PPPD) varies among surgeons. We compared and evaluated
      three different definitions reported elsewhere. In addition, we investigated the
      correlation between multiple surgical factors and recovery of gastric motility.
      First, 55 consecutive patients were reviewed to assess the three different
      definitions. Second, surgical factors affecting gastric motility were
      investigated in 46 patients showing no major complications. All 55 patients
      underwent PPPD, which was reconstructed with antecolic duodenojejunostomy, with
      aggressive lymph node dissection and with no mortality. The duration of
      nasogastric intubation was 2 days, and a solid diet started on the 12th
      postoperative day (median). Re-nasogastric intubation or emesis was observed in
      12.7% of patients. Overall, DGE occurrence rate was 5.5%-29.1%, with striking
      differences depending on the type of definition. Technically, division of the
      left gastric vein was accompanied with significantly delayed removal of the
      nasogastric tube (3 versus 2 days, P = 0.0002) and delayed start on a solid diet
      (14 versus 9 days, P < 0.0001) compared with its preservation. Antecolic
      duodenojejunostomy after PPPD improved DGE occurrence despite aggressive surgery,
      and preservation of LGV accelerated restoration of gastric motility in our
      experiments. However, an understanding of a common definition of DGE is needed
      when discussing the outcome of the various interventions.

PMID- 15985245
TI  - Successful preoperative diagnosis and complete resection of biliary intraductal
      papillary-mucinous neoplasm of the liver.

PMID- 15985244
TI  - Management of hepatic hemangiomas: a 14-year experience.
AB  - Hemangioma is the most common primary tumor of the liver and its diagnosis has
      become increasingly prevalent. Most of these lesions are asymptomatic and are
      managed conservatively. Large hemangiomas are often symptomatic and reports of
      surgical intervention are becoming increasingly frequent. We present our
      experience, over the last 14 years, with diagnosis and management of 249 liver
      hemangiomas, with special attention to a conservative strategy. Clinical
      presentation, diagnosis, treatment, and long-term outcome are analyzed. Of 249
      patients, 77 (30.9%) were symptomatic, usually with right abdominal upper
      quadrant pain. Diagnosis was based on a radiologic algorithm according to the
      size and characteristics of the tumor; diagnosis by this method was not possible
      in only one case (0.4 %). Giant hemangiomas (>4 cm) were found in 68 patients
      (27.3%) and in 16 were larger than 10 cm. Eight patients (3.2%) underwent
      surgical treatment; indications were incapacitating pain in 6, diagnostic doubt
      in 1, and stomach compression in 1. No postoperative complications or mortality
      were observed in this series. Patients who did not undergo surgery (n = 241) did
      not present any complication related to the hemangioma during long-term follow-up
      (mean = 78 months). Hemangioma is a benign course disease with easy diagnosis and
      management. We propose a conservative approach for these lesions. Resection,
      which can be safely performed, should be reserved for the rare situations such as
      untreatable pain, diagnostic uncertainty, or compression of adjacent organs.

PMID- 15985246
TI  - Changing concepts in the management of liver hydatid disease.
AB  - Hydatid disease is a rare entity primarily affecting the population of developing
      countries. The parasite shuttles between the liver and lungs. but almost any
      organ can be invaded, forming cysts. Septation and calcification of the cysts
      with a high antibody titre in the patient's serum confirm the diagnosis, although
      more sophisticated tests have been applied recently. Surgery constitutes the
      primary treatment, with a variety of techniques based on the principles of
      eradication and elimination of recurrence by means of spillage avoidance.
      Minimally invasive techniques and percutaneous drainage of the cysts are now
      feasible because of progress in the field. The aim of this review is to collect
      the experience from three different institutions and to provide practical
      guidelines for diagnostic and therapeutic strategies.

PMID- 15985247
TI  - A disappearing hepatic infusion pump.

PMID- 15985249
TI  - Hysterectomy: evolution and trends.
AB  - Hysterectomy was mentioned in Greek manuscripts 2000 years ago, but there is no
      proof that it was performed. Early--usually fatal--attempts at vaginal
      hysterectomy are recorded from the 16th century. The origins of vaginal and
      abdominal hysterectomy are traced from the 19th century after the pioneering work
      of Langenbeck and Clay. Advances in anaesthesia, blood transfusion, antibiotics
      and surgical technique led to hysterectomy becoming the second most common
      operation in women. In the first part of the 20th century subtotal abdominal
      hysterectomy was standard, but by the 1950s this was replaced by total abdominal
      hysterectomy. There has been a recent, albeit minor, resurgence of interest in
      subtotal hysterectomy. The development of laparoscopic assisted hysterectomy in
      the 1990s has, ironically, led to the re-emergence of standard vaginal
      hysterectomy as the method of choice for most cases of benign gynaecological
      disease requiring hysterectomy. At the start of the 21st century there are signs
      that alternatives to hysterectomy-such as hysteroscopic surgery, uterine fibroid
      embolization, and the levonorgestrel intrauterine device-are leading to a
      reduction in hysterectomy rates.

PMID- 15985250
TI  - Vaginal hysterectomy.
AB  - The vaginal route is a safe, feasible, and patient-friendly method of performing
      a hysterectomy. Proponents and practitioners of vaginal hysterectomy have widened
      their indications and decreased the contraindications through liberal usage of
      debulking, performing oophorectomy, laparoscopic evaluation and trial vaginal
      hysterectomy. This traditional approach with surgical advances can be used more
      frequently.

PMID- 15985251
TI  - Total and subtotal abdominal hysterectomy.
AB  - Hysterectomy is one of the most frequently performed operations in the world,
      accounting for 500,000-600,000 procedures annually in the USA; the abdominal
      route for hysterectomy is the preferred route in 60-80% of these operations.
      Although the number of total abdominal hysterectomies performed annually has
      decreased, the number of subtotal abdominal hysterectomies increased by >400%.
      The major indications for abdominal hysterectomy include abnormal uterine
      bleeding, myomata uteri, adenomyosis, endometriosis, neoplasia, and chronic
      salpingitis. The basis for selection for subtotal versus total hysterectomy has
      little in the way of factual data to support it and may actually present some
      significant disadvantages, such as continued menstruation and cervical prolapse.
      The detailed technique for performing intrafascial abdominal hysterectomy relies
      heavily on precise knowledge of pelvic anatomy and compulsive detail to tissue
      handling. The consistent and correct usage of prophylactic antimicrobials,
      measures to prevent thromboemboli, and procedures to avoid urinary retention are
      key to the overall success of the surgery.

PMID- 15985252
TI  - Laparoscopic hysterectomy for benign diseases.
AB  - Despite more than 1000 publications on laparoscopic hysterectomy (LH), its role
      remains difficult to define. LH is not there to replace vaginal hysterectomy, but
      may be an alternative for abdominal hysterectomy when there are (relative)
      contraindications for vaginal hysterectomy, including concomitant oophorectomy,
      previous pelvic surgery and/or risk for adhesions, the larger uterus and
      nulliparity, and some oncological indications. Randomized trials have
      demonstrated that, compared to abdominal hysterectomy, LH shortens hospital stay
      and induces less postoperative pain and quicker recovery at the expense of a
      longer operation time. LH carries a higher risk for adjacent organ injury, and
      may be cost-effective, despite higher direct costs, because of the shorter
      hospital stay and quicker recovery.

PMID- 15985253
TI  - Laparoscopically assisted vaginal radical hysterectomy.
AB  - Young patients affected by an early-stage invasive cancer of the cervix are
      usually treated by surgery. Abdominal radical hysterectomy with pelvic
      lymphadenectomy is the most widely used technique. With the advent of more
      conservative surgical approaches, laparoscopy has gained acceptance in
      gynecologic oncology, opening the way for radical vaginal surgery for cervical
      cancer. Before this technique becomes widely accepted, it has to be demonstrated
      that the results, in terms of safety and efficacy, are comparable with the
      'standard' abdominal approach. In this chapter we review the technique of
      laparoscopically assisted radical vaginal hysterectomy and evaluate results of
      published series.

PMID- 15985254
TI  - Radical hysterectomy.
AB  - The radical hysterectomy is the standard approach for the treatment of women with
      early cervical cancer. However, it has increasingly been recognized that a more
      individualized approach to treatment should be taken. In particular, careful
      pretreatment evaluation should reduce the number of women receiving adjuvant
      radiotherapy. Laparoscopic lymphadenectomy is an attractive technique that seems
      likely to reduce the use of dual modality therapy. The laparoscopic approach to
      the evaluation of lymph nodes in cervical cancer has also allowed the development
      of the fertility-preserving radical trachelectomy. Outcomes for women with early
      cervical cancer are generally good, and it therefore becomes increasingly
      relevant to develop methods of reducing long-term morbidity.

PMID- 15985255
TI  - Hysterectomy and pelvic organ dysfunction.
AB  - Contrary to popular belief, there is now considerable evidence that simple
      abdominal hysterectomy does not adversely affect bladder, bowel and sexual
      function (collectively referred to as 'pelvic organ function'). This also appears
      to hold true for vaginal hysterectomy, although randomized studies are lacking.
      Furthermore, conservation of the cervix by performing a subtotal (supracervical)
      hysterectomy does not confer advantages over total hysterectomy as far as pelvic
      organ function is concerned. By contrast, as radical hysterectomy involves more
      extensive dissection of the pelvic organs and innervation, some degree of pelvic
      organ dysfunction might be expected. However, the small prospective studies
      available provide conflicting results, but major sexual problems after radical
      hysterectomy appear to be transient. Retrospective studies suggest that abdominal
      and particularly vaginal hysterectomy may predispose to vault prolapse. One study
      reported that subtotal hysterectomy may be associated with subsequent cervical
      prolapse. These issues can only be clarified when long-term follow-up of recently
      completed randomized trials are performed. Until then, myths regarding the most
      frequently performed major gynaecological operation need to be dispelled, and
      women requiring hysterectomy should be counselled using the best available
      evidence.

PMID- 15985256
TI  - Hysterectomy: effects on quality of life and psychological aspects.
AB  - Most gynaecological disorders are not life-threatening. They may nevertheless
      severely affect women's quality of life. The majority of hysterectomies are
      performed to treat non-malignant conditions, to enhance the quality of life
      rather than save life. Recent research shows an enhancement in quality of life
      during the early years after hysterectomy. Furthermore, research shows that
      hysterectomy does not cause any adverse psychological outcome in otherwise
      psychologically healthy women, but presurgical psychopathology is predictive of
      postsurgical psychopathology. Research also shows that most gynaecological cancer
      survivors enjoy a relatively good quality of life.

PMID- 15985257
TI  - Alternative medical and surgical options to hysterectomy.
AB  - The range of alternatives to hysterectomy includes 'expanded' oral medical
      regimens, the levonorgestrel-releasing intrauterine system (LNG-IUS), a wide
      range of endometrial ablative techniques, and-where fibroids are the primary
      pathology-myomectomy and uterine artery embolization. Since research has shown
      that hysterectomy is a highly effective treatment, these alternatives must be
      assessed against the recognized high satisfaction rates and improved quality of
      life reported following hysterectomy. Additional issues that would also need to
      be addressed include complication rates, side-effects, and cost-effectiveness.
      For women with prolonged abnormal uterine bleeding, recent research suggests that
      hysterectomy is significantly superior to an expanded medical treatment regimen
      for health-related quality-of-life measures. Satisfaction with treatment, and
      health-related quality of life and psychosocial well-being, are reportedly
      similar between hysterectomy and the LNG-IUS, but the latter has the advantage of
      reduced cost. Endometrial ablation reduces menstrual blood flow, but its benefits
      relative to hysterectomy lessen over time. No large-scale studies have adequately
      compared uterine artery embolization or myomectomy to hysterectomy. Perhaps the
      most telling finding from recent research with respect to the place of
      alternative therapies to hysterectomy is that the existence or advent of these
      alternatives has not reduced hysterectomy rates, but merely increased treatment
      options and interventions for excessive menstrual loss.

PMID- 15985258
TI  - Health economics of hysterectomy.
AB  - Health resources are finite, and it is increasingly necessary to practise
      medicine within defined budgets. Hysterectomy is recognized as one of the most
      frequently performed of all major surgical operations and is of great economic as
      well as medical and social importance. A full assessment of the value of an
      intervention requires consideration of both economic and clinical outcomes. New
      alternative therapies to uterine excision have been introduced, and new ways of
      performing hysterectomy have been developed. Cost-effectiveness analysis enables
      each of these approaches to be meaningfully compared. Using such analytic
      techniques, hysterectomy can be shown to be an effective and cost-effective
      intervention across a variety of indications. The vaginal route is the most cost
      effective approach. There seems to be no obvious advantage in conserving or
      retaining the cervix, but there is as yet no evidence about the cost
      effectiveness of concomitant oophorectomy.

PMID- 15985259
TI  - Seasonal fluctuations of phlebotomine sand fly populations (Diptera: Psychodidae)
      in the urban area of Marrakech, Morocco.
AB  - Phlebotomine sand flies (Diptera: Psychodidae) were collected continuously, using
      sticky traps, during 1 year from October 2002 to September 2003, in an urban area
      of Marrakech city (Morocco). A total of 3277 specimens were collected belonging
      to five species. Phlebotomus (Phlebotomus) papatasi (54.6%) is the predominant
      species followed by Sergentomyia (Sergentomyia) minuta (20%), S. (S.) fallax
      (11.3%), P. (Paraphlebotomus) sergenti (10.3%) and P. (Larroussius) longicuspis
      (3.8%). Data analyses showed a mono-modal annual pattern for P. sergenti and a bi
      modal one for the other species. P. papatasi, the proven vector of Leishmania
      major in Morocco, was active throughout the year. This species did not diapause
      in this region. P. papatasi population peaked in June and November, which
      relating to the periods of risk in this area. Its preferred temperature ranged
      between 32 and 36 degrees C but no significant correlation was found between its
      density and the temperature. Considering the high density and long activity
      period of P. papatasi, the area of Marrakech should be regarded as a potential
      focus for L. major. This suggests the need for a continuously surveillance to
      prevent risk of zoonotic cutaneous leishmaniasis.

PMID- 15985260
TI  - In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5
      HT1A receptors.
AB  - This study determined the in vitro functional profile of 1-[3-[4-(3-chlorophenyl)
      1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate
      (OPC-14523) at rat and human serotonin (5-HT) 5-HT1A receptors and binding
      affinity of OPC-14523 at human frontocortical 5-HT1A receptors. OPC-14523 (1
      microM) increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS)
      binding to 5-HT1A receptor-containing regions of rat brain tissue sections
      (approximately 53% of the effect of 1 microM (+)8-hydroxy-2-(di-n
      propylamino)tetralin ((+)8-OH-DPAT) that were blocked by the selective 5-HT1A
      receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2
      pyridinylcyclohexanecarboxamide (WAY-100635). OPC-14523 also behaved as a partial
      agonist in its stimulation of [35S]GTPgammaS binding to membranes from rat
      hippocampus (pEC50=7.60+/-0.23, Emax=41.1% of the effect of 10 microM (+)8-OH
      DPAT), human frontal cortex (pEC50=7.89+/-0.08; Emax=64% of the effect of 10
      microM (+)8-OH-DPAT), and Chinese Hamster Ovary cells expressing cloned human 5
      HT1A receptors (pEC50=8.0+/-0.11; Emax=85.5% of the effect of 10 microM 5-HT),
      and all of these effects of OPC-14523 were blocked by WAY-100635. Taken together,
      these data support the development of OPC-14523 as an antidepressant whose
      mechanism of action involves potent partial agonist activity at 5-HT1A receptors.

PMID- 15985261
TI  - Prostaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18
      production in monocytes.
AB  - The purpose of this present study was to explore the therapeutic potential of
      prostaglandins E1 and E2 on the systemic inflammatory response evoked by
      endotoxin. Since interleukin-18, a monocyte-derived cytokine, is increased during
      sepsis, decreasing the production of interleukin-18 is important in treating this
      condition. Prostaglandin E1 and E2 inhibited interleukin-18 production in human
      monocytes treated with lipopolysaccharide and prostanoid IP-, EP2- and EP4
      receptor agonists mimicked the effects of prostaglandins E1 and E2. Therefore,
      prostanoid IP, EP2- and EP4-receptors might be involved in the decrease in
      interleukin-18 production during sepsis.

PMID- 15985262
TI  - Comparative relaxant effects of YC-1 and DETA/NO on spontaneous contractions and
      the levels of cGMP of isolated pregnant rat myometrium.
AB  - This study was designed to compare the effects of YC-1 (3-(5'-hydroxymethyl-2'
      furyl)-1-benzyl indazole), a nitric oxide (NO)-independent soluble guanylate
      cyclase activator, and diethylenetriamine-NONOate (DETA/NO), a NO donor, on
      spontaneous contractions and the levels of cyclic GMP (cGMP) of myometrial strips
      isolated from timed-pregnant rats. Myometrial strips were obtained from timed
      pregnant Wistar albino rats (n=10) and were mounted in organ baths and tested for
      changes in isometric tension in response to YC-1 and DETA/NO. We also evaluated
      the effect of YC-1 and DETA/NO on the levels of cGMP in myometrial strips
      obtained from timed-pregnant rat uterine horns (n=20). YC-1 (10(-9)-3x10(-5) M)
      and DETA/NO (10(-7)-10(-4) M) concentration-dependently decreased the amplitude
      and frequency of spontaneous contractions of myometrial strips isolated from term
      pregnant rats. The inhibitions of the amplitude and frequency of spontaneous
      contractions by YC-1 and DETA/NO were antagonized with methylene-blue (10(-5) M).
      Antagonistic effect of methylene-blue (10(-5) M) was more on DETA/NO responses
      than that of YC-1 (P<0.05). In addition, YC-1-stimulated myometrial strips showed
      more elevation in myometrial cGMP than that of DETA/NO (P<0.05). We demonstrated
      that YC-1 and DETA/NO induce relaxations in the amplitude and frequency of
      spontaneous contractions of myometrial strips with different potencies. We also
      found that YC-1 and DETA/NO-induced relaxations are associated with significant
      increases in cGMP. These results might suggest that the relaxant effects of YC-1
      and DETA/NO on the rat myometrium could be due to the stimulation of the soluble
      guanylate cyclase and cGMP may play a role for the maintenance of uterine
      quiescence during pregnancy.

PMID- 15985263
TI  - Ultrasonic vocalization production of preweanling rats: effects of central and
      peripheral administration of alpha2-adrenoceptor agonists.
AB  - Stimulation of alpha2-adrenoceptors increases the ultrasonic vocalization
      production of preweanling rats, however it is not known whether these critical
      alpha2-adrenoceptors are located peripherally or centrally. In a series of three
      experiments, ultrasonic vocalizations were measured after 11-day-old rats had
      been administered clonidine or 2-[2,6-diethylphenylamino]-2-imidazole (ST-91)
      either systemically (i.p.) or into the third ventricle (i.c.v.). These particular
      alpha2-adrenoceptor agonists were chosen because clonidine is lipophilic and
      enters the central nervous system, while ST-91 is hydrophilic and does not
      readily cross the blood-brain barrier. In the third experiment, clonidine- (1
      microg, i.c.v.) and ST-91-induced (15 microg, i.c.v.) ultrasonic vocalizations
      were measured after systemic injection of the alpha2-adrenoceptor antagonist
      yohimbine (0.5 or 1 mg/kg, i.p.). Results showed that central administration of
      both clonidine and ST-91 increased the ultrasonic vocalization production of 11
      day-old rats, whereas peripheral administration of only clonidine, and not ST-91,
      increased ultrasonic vocalizations. These results indicate that the alpha2
      adrenoceptors mediating ultrasonic vocalization production are located in the
      central nervous system. Yohimbine fully attenuated clonidine-induced ultrasonic
      vocalizations but only partially attenuated ST-91-induced vocalizations. This
      pattern of results may have been due to the differential selectivity of clonidine
      and ST-91 for alpha2-adrenoceptor subtypes (alpha2A, alpha2B, and alpha2C) or
      imidazoline receptors. When combined with past research, the present results are
      consistent with the hypothesis that centrally located alpha2-adrenoceptors are a
      component of a neural system that mediates ultrasonic vocalization production.

PMID- 15985264
TI  - The locking compression plate in periprosthetic humeral fractures A review of two
      cases.

PMID- 15985265
TI  - Mechanical compression and hydrostatic pressure induce reversible changes in
      actin cytoskeletal organisation in chondrocytes in agarose.
AB  - In numerous cell types, the cytoskeleton has been widely implicated in
      mechanotransduction pathways involving stretch-activated ion channels, integrins
      and deformation of intracellular organelles. Studies have also demonstrated that
      the cytoskeleton can undergo remodelling in response to mechanical stimuli such
      as tensile strain or fluid flow. In articular chondrocytes, the
      mechanotransduction pathways are complex, inter-related and as yet, poorly
      understood. Furthermore, little is known of how the chondrocyte cytoskeleton
      responds to physiological mechanical loading. This study utilises the well
      characterised chondrocyte-agarose model and an established confocal image
      analysis technique to demonstrate that both static and cyclic, compressive strain
      and hydrostatic pressure all induce remodelling of actin microfilaments. This
      remodelling was characterised by a change from a uniform to a more punctate
      distribution of cortical actin around the cell periphery. For some loading
      regimes, this remodelling was reversed over a subsequent 1h unloaded period. This
      reversible remodelling of actin cytoskeleton may therefore represent a mechanism
      through which the chondrocyte alters its mechanical properties and
      mechanosensitivity in response to physiological mechanical loading.

PMID- 15985266
TI  - Anxiolytic effect of Gardeniae Fructus-extract containing active ingredient from
      Kamishoyosan (KSS), a Japanese traditional Kampo medicine.
AB  - Kamishoyosan (KSS), a Kampo formula used to treat menopausal psychotic syndromes
      in women, consists of ten crude herbal drugs. The anxiolytic effect of KSS was
      investigated by the social interaction (SI) test using mice, and whether the
      effect of KSS was due to the stimulating and/or sedating effects was examined by
      the open field locomotion test. Furthermore, the present study examined the
      effect of individual crude drugs in KSS by the SI test to clarify its active
      components. Oral administration of KSS increased the total SI time in a dose
      dependent manner (50--200 mg/kg), but this effect was not observed over a dose of
      300 mg/kg. On the other hand, there were no significant changes observed for the
      open field locomotion test. These results suggest that the appearance of KSS
      induced SI behavior is due to an anxiolytic effect. The unaltered results of the
      open field test indicated that KSS was neither a stimulant nor sedative. To
      identify the essential herbs in KSS, the effects of "the component herbs in KSS"
      and "KSS minus one component herb" using the SI test were examined. An increase
      in the SI time was observed for hot water extracts of Menthae herba and Gardeniae
      Fructus, the same as for the KSS treatment. On the other hand the effect of KSS
      on the SI time was reduced to the control level for KSS minus Gardeniae Fructus,
      KSS minus Paeoniae Radix, KSS minus Glycyrrhizae Radix and KSS minus Hoelen. Oral
      administration of Gardeniae Fructus-extract or its common constituent, geniposide
      increased the SI time in a dose-dependent manner. These results indicate that
      Gardeniae Fructus and geniposide play a role in the anxiolytic effect of KSS.

PMID- 15985267
TI  - Hydralazine decreases sodium nitroprusside-induced rat aortic ring relaxation and
      increased cGMP production by rat aortic myocytes.
AB  - Association of hydralazine with nitrova-sodilators has long been known to be
      beneficial in the vasodilator treatment of heart failure. We previously found
      that hydralazine appeared to reduce the increase in cGMP induced by sodium
      nitroprusside in cultured rat aortic myocytes. In order to further explore this
      seemingly paradoxical interaction, we extended our initial observations in rat
      aortic myocytes and also determined the influence of hydralazine on sodium
      nitroprusside-induced relaxation of rat aortic rings. Hydralazine produced a
      concentration-dependent inhibition of sodium nitroprusside stimulation of cGMP
      production and caused a rightward shift of concentration-relaxation curves in
      aortic rings. A possible mechanism of the hydralazine-nitroprusside interaction
      could be the interference with bioactivation of the nitro-vasodilator to release
      nitric oxide. Recent evidence indicates that vascular NADH oxidase, an enzyme
      known to be inhibited by hydralazine, could be involved in this process.
      Accordingly, hydralazine was found to inhibit NADH oxidase activity in rat aortic
      myocytes at concentrations similar to those reducing sodium nitroprusside
      responses. It was concluded that antagonism of sodium nitroprusside action by
      hydralazine could be a consequence of interference with bioactivation of the
      former, apparently through inhibition of vascular NADH oxidase.

PMID- 15985269
TI  - Involvement of calcium-dependent mechanisms in T3-induced phosphorylation of
      vimentin of immature rat testis.
AB  - Thyroid hormones have been shown to act at extra nuclear sites, inducing target
      cell responses by several mechanisms, frequently involving intracellular calcium
      concentration. It has also been reported that cytoskeletal proteins are a target
      for thyroid and steroid hormones and cytoskeletal rearrangements are observed
      during hormone-induced differentiation and development of rat testes. However,
      little is known about the effect of 3,5,3'-triiodo-L-thyronine (T3) on the
      intermediate filament (IF) vimentin in rat testes. In this study we investigated
      the immunocontent and in vitro phosphorylation of vimentin in the cytoskeletal
      fraction of immature rat testes after a short-term in vitro treatment with T3.
      Gonads were incubated with or without T3 and 32P orthophosphate for 30 min and
      the intermediate filament-enriched cytoskeletal fraction was extracted in a high
      salt Triton-containing buffer. Vimentin immunoreactivity was analyzed by
      immunoblotting and the in vitro 32P incorporation into this protein was measured.
      Results showed that 1 microM T3 was able to increase the vimentin
      immunoreactivity and in vitro phosphorylation in the cytoskeletal fraction
      without altering total vimentin immunocontent in immature rat testes. Besides,
      these effects were independent of active protein synthesis. The involvement of
      Ca2+-mediated mechanisms in vimentin phosphorylation was evident when specific
      channel blockers (verapamil and nifedipine) or chelating agents (EGTA and BAPTA)
      were added during pre-incubation and incubation of the testes with T3. The effect
      of T3 was prevented when Ca2+ influx was blocked or intracellular Ca2+ was
      chelated. These results demonstrate a rapid nongenomic Ca2+-dependent action of
      T3 in phosphorylating vimentin in immature rat testes.

PMID- 15985268
TI  - Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of
      vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma
      cells.
AB  - Pigment epithelium-derived factor (PEDF) has been shown to be the most potent
      inhibitor of angiogenesis in the mammalian eye, thus suggesting that loss of PEDF
      is involved in angiogenic eye diseases such as proliferative diabetic
      retinopathy. Angiogenesis is required for tumor growth and progression as well.
      We, along with others, have recently found that PEDF could inhibit growth of
      melanoma and hepatocellular carcinoma in nude mice through its anti-angiogenic
      effects on tumor endothelial cells. However, the possibility of the direct effect
      of PEDF on tumor cells has remained. In this study, we investigated the effects
      of PEDF on growth and vascular endothelial growth factor (VEGF) expression in
      MG63 human cultured osteosarcoma cells. PEDF decreased viable cell number as well
      as DNA synthesis in MG63 cells in a dose-dependent manner. Furthermore, PEDF was
      found to increase caspase-3/7 activity and to subsequently induce apoptotic cell
      death in MG63 cells. PEDF also inhibited VEGF expression in MG63 cells at both
      mRNA and protein levels. Our present study provides novel beneficial aspects of
      PEDF on osteosarcoma cells; one is induction of apoptotic cell death of tumor
      cells, and the other is the suppression of VEGF expression, which would lead to
      inhibition of tumor angiogenesis. PEDF therefore might be a promising therapeutic
      agent for treatment of patients with osteosarcoma.

PMID- 15985270
TI  - Nociceptin/orphanin FQ: pain, stress and neural circuits.
AB  - First isolated some 10 years ago as the endogenous ligand for the "orphan opioid
      receptor" (ORL-1, now designated NOP), nociceptin/orphanin FQ (N/OFQ) has proved
      to be a potent inhibitory neuropeptide found across the neuraxis. Because of the
      homologies between opioids and N/OFQ, functional studies of this peptide have
      focused most heavily on pain and analgesia. This behavioral literature has been
      marked by a lack of consistency across laboratories, but much of the data can be
      explained by considering the potent inhibitory actions of N/OFQ in well-defined
      modulatory circuits. Presently, the most closely studied such circuit is the
      rostral ventromedial medulla (RVM), where administration of N/OFQ can block
      opioid analgesia (by inhibiting opioid-activated pain-inhibiting neurons), but
      under other conditions produces apparent hypoalgesia (by inhibiting pain
      facilitating neurons). The net behavioral effect of N/OFQ in the RVM thus depends
      on whether experimental conditions are such that the pain-facilitating or pain
      inhibiting neurons are active at the time the peptide is given. An important
      recent finding is that N/OFQ antagonists have antinociceptive properties when
      given supra-spinally. Although the likelihood of interactions between stress and
      analgesia systems must be considered in interpreting these data, they suggest
      that N/OFQ antagonists have potential as clinically useful analgesic drugs.

PMID- 15985271
TI  - Lymphocyte DNA damage in patients with acute coronary syndrome and its
      relationship with severity of acute coronary syndrome.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      lymphocyte DNA damage and acute coronary syndromes (ACS). METHODS: The study
      population contained 53 patients with ACS, 48 patients with stable angina and 35
      voluntary healty subjects. DNA damage was assessed by alkaline comed assay in
      peripheral lymphocyte and plasma levels of total antioxidant capacity (TAC) were
      determined using a novel automated measurement method. RESULTS: In ACS patients,
      DNA damage was significantly higher than in patients with stable angina and
      control subjects (144+/-52 AU, 116+/-37, 68+/-34 AU; for three p<0.001,
      respectively). The TAC levels in patients with ACS were lower than the other
      groups (1.24+/-0.31 mmol Trolox equiv./l, 1.46+/-0.29 mmol Trolox equiv./l,
      p<0.05, respectively). DNA damage values in patients with acute miyocardial
      infarction were significantly higher than in patients with unstable angina
      (159.8+/-53.0 AU versus 131.8+/-48.4 AU; p<0.05, respectively). Lymphocyte DNA
      damage values in patients with ACS showed positive correlation with d-dimer
      (r=0.880, p<0.001) troponin I (r=538, p<0.001) and C-reactive protein (r=0.544,
      p<0.001) and negative correlation with TAC (r=-0.346, p=0.011). In multiple
      linear regression analysis, TAC (beta=-0.213, p=0.001) and d-dimer (beta=0.697,
      p<0.001) were independent predictors of DNA damage in patients with ACS.
      CONCLUSIONS: These findings indicate that lymphocyte DNA damage level increases
      in patients with ACS. Elevated DNA damage may be related with plaque instability
      and be useful for the identification of patients with acute coronary syndromes.

PMID- 15985272
TI  - Increased temporal lobe gyrification in preterm children.
AB  - Preterm birth often results in significant learning disability, and previous
      magnetic resonance imaging (MRI) studies of preterm children have demonstrated
      reduction in overall cortical tissue with particular vulnerability in the
      temporal lobe. We measured cortical gyrification in 73 preterm and 33 term
      control children at 8 years of age and correlated these findings with tests of
      language ability to determine the associations among preterm birth,
      neurodevelopment and functional outcome. Preterm children demonstrated
      significantly increased bilateral temporal lobe gyrification index compared to
      term controls. Left temporal gyrification index was significantly negatively
      correlated with left temporal lobe gray matter volume as well as reading
      recognition scores in the preterm group. Cortical development in the temporal
      lobe appears to be differentially vulnerable to preterm birth.

PMID- 15985273
TI  - Effects of baseline task position on apparent activation in functional imaging of
      memory.
AB  - Brain activation dissociates during the repeated performance of memory tasks with
      decreasing medial temporal and increasing orbitofrontal activation. The impact of
      such adaptations on a baseline task is unknown. In this study, we used H2(15)O
      positron emission tomography (PET) in two groups of subjects performing a
      continuous recognition task and a baseline task. The group performing the
      baseline task after the main task showed significant medial temporal activation
      in the subtraction (recognition task-baseline). The group performing the baseline
      task at the beginning showed right orbitofrontal activation. These differences
      appeared to result primarily from different activations during the baseline task.
      It thus appears that the temporal context of a baseline task may fundamentally
      alter cognitive requirements and substantially influence apparent brain
      activation during a memory task. We suggest that the automatic filtration of
      memories according to their relevance for ongoing reality, a capacity mediated by
      the orbitofrontal cortex, is one such influence on apparent activation.

PMID- 15985274
TI  - Effect of periodical water current on the phasing of demand feeding rhythms in
      sea bass (Dicentrarchus labrax L.).
AB  - The demand feeding rhythms of sea bass (Dicentrarchus labrax L.) maintained at
      rest or subjected to exercise (increase in swimming activity) as a result of an
      induced water current are compared. Both sea bass kept individually and in group
      (4 and 8 individuals) shifted their food demands towards the exercise period or
      to just after the same (the latter especially in individually kept fish). The
      origin of such a response is discussed in view of innate behaviour, the energy
      cost of locomotor activity and changes in agonistic behaviour. Induced diurnal
      exercise favoured diurnal feeding. The periodic exercise regime led to lower
      rates of daily feeding pattern inversions (diurnal-to-nocturnal or vice-versa).
      Sea bass were capable of learning to press an exercise sensor and to
      distinguishing exercise sensors from demand feeding sensors.

PMID- 15985275
TI  - Measuring lymphocyte kinetics in tropical field settings.
AB  - Studies involving in-vivo labelling of lymphocyte DNA with 6,6-2H2-glucose to
      track T-cell turnover have contributed to understanding lymphocyte homeostasis in
      health and disease. Applying such studies in tropical settings (where diseases
      that affect T-cells are prevalent) requires protocol modifications including non
      intravenous label administration, applicability in outpatient facilities, and T
      cell sorting methods independent of a fluorescence activated cell sorter (FACS).
      Such protocols were validated in UK pilot studies and applied in The Gambia.
      Healthy adult subjects (n=12) were recruited from three Gambian villages. 6,6-2H2
      glucose was administered orally in an outpatient clinic and T-cell subpopulations
      isolated from peripheral blood using plastic adherence, and Multisorttrade mark
      magnetic cell sorting (MACStrade mark) to obtain CD8+CD45R0+, CD8-CD45R0+,
      CD8+CD45R0- and CD8-CD45R0- subsets. To achieve high cell purity and yield,
      CD45R0- cells were reincubated with CD45R0 beads. T-cell proliferation and
      disappearance were quantified using gas chromatography mass spectrometry. Results
      were consistent with those of other studies showing higher turnover in memory
      (CD45R0+) than in naive (CD45R0-) T-cell subsets, and an association between
      recent cell proliferation and susceptibility to cell death. Cell kinetics
      research is applicable in tropical settings, and can contribute to further
      understanding the regulation of adaptive immunity in response to infections and
      other insults.

PMID- 15985276
TI  - Trihalomethanes aqueous solutions sono-oxidation.
AB  - Ultrasonic (US) irradiation, hydrogen peroxide (H(2)O(2)), Fenton's oxidation and
      the combination of the processes were investigated for destruction and removal of
      the following trihalomethanes (THMs) compounds from aqueous solutions: CHCl(3),
      CHBrCl(2), CHBr(2)Cl, CHBr(3), and CHI(3). H(2)O(2) had no significant effect on
      the THMs sonodegradation. The coupled US and Fenton processes did not affect the
      CHCl(3), CHBrCl(2), and CHBr(2)Cl sonolysis efficiency. Nevertheless, the
      sonodegradation of CHBr(3) was enhanced. CHI(3) was degraded by Fenton's
      oxidation rather than by the US irradiation during the sonication/Fenton
      treatment. The combination of sonication with H(2)O(2) or Fenton's reagent did
      not affect the mineralization of the THMs aqueous mixture.

PMID- 15985277
TI  - Adsorption of residue oil from palm oil mill effluent using powder and flake
      chitosan: equilibrium and kinetic studies.
AB  - The adsorption of residue oil from palm oil mill effluent (POME) using chitosan
      powder and flake has been investigated. POME contains about 2g/l of residue oil,
      which has to be treated efficiently before it can be discharged. Experiments were
      carried out as a function of different initial concentrations of residue oil,
      weight dosage, contact time and pH of chitosan in powder and flake form to obtain
      the optimum conditions for the adsorption of residue oil from POME. The powder
      form of chitosan exhibited a greater rate compared to the flake type. The results
      obtained showed that chitosan powder, at a dosage of 0.5g/l, 15min of contact
      time and a pH value of 5.0, presented the most suitable conditions for the
      adsorption of residue oil from POME. The adsorption process performed almost 99%
      of residue oil removal from POME. Equilibrium studies have been carried out to
      determine the capacity of chitosan for the adsorption of residue oil from POME
      using the optimum conditions from the flocculation at different initial
      concentrations of residue oil. Langmuir and Freundlich adsorption models were
      applied to describe the experimental isotherms and isotherm constants.
      Equilibrium data fitted very well with the Freundlich model. The pseudo first-
      and second-order kinetic models and intraparticle diffusion model were used to
      describe the kinetic data and the rate constants were evaluated. The experimental
      data fitted well with the second-order kinetic model, which indicates that the
      chemical sorption is the rate-limiting step, i.e. chemisorption between residue
      oil and chitosan. The significant uptake of residue oil on chitosan was further
      proved by BET surface area analysis and SEM micrographs.

PMID- 15985278
TI  - Kinetics and mechanisms of formation of bromophenols during drinking water
      chlorination: assessment of taste and odor development.
AB  - Halophenols are often reported as off-flavor causing compounds responsible for
      medicinal taste and odor episodes in drinking water. To better understand and
      minimize the formation of 2-bromophenol and 2,6-dibromophenol which have low odor
      threshold concentrations (OTCs, 30 and 0.5 ng/L, respectively) a kinetic data
      base for the chlorination and bromination of phenols was established by
      combination of kinetic measurements and data from literature. Second-order rate
      constants for the reactions of chloro- and bromophenols with chlorine and bromine
      were determined over a wide pH range. The second-order rate constants for
      bromination of phenols are about three orders of magnitude higher than for
      chlorination. A quantitative structure activity relationship (QSAR) showed a good
      comparability of second-order rate constants from this study with those published
      previously for different phenol derivatives. The quantification of product
      distribution of the formed halophenols demonstrated that chlorine or bromine
      attack in ortho position is favored with respect to the para position. A kinetic
      model was formulated allowing us to investigate the influence of chlorine dose
      and some water quality parameters such as the concentration of phenol, ammonia,
      bromide and the pH on the product distribution of halophenols. The kinetic model
      can be applied to optimize drinking water chlorination with respect to phenol
      born taste and odor problems. In general, high chlorine doses lead to low
      concentrations of intermediate odorous chlorophenols and bromophenols. An
      increase in the ammonia or phenol concentration leads to a higher consumption of
      HOCl and therefore greater final concentration of intermediate bromophenols. The
      presence of higher bromide than phenol concentration also facilitates the rapid
      bromination pathway which leads to further bromination of 2,6-dibromophenol to
      higher brominated phenols. Laboratory-scale experiments on taste and odor
      formation due to the chlorination of phenol- and bromide-containing waters have
      confirmed the trend of the model calculations.

PMID- 15985279
TI  - Maternal-fetal distribution and transfer of dioxins in pregnant women in Japan,
      and attempts to reduce maternal transfer with Chlorella (Chlorella pyrenoidosa)
      supplements.
AB  - Dioxins can be transferred from mother to fetus via the placenta, or to nursing
      infants via breast milk, potentially causing developmental health problems in
      children. To assess pediatric health risks from dioxins, exposure of mothers and
      children to dioxins must be clarified. Methods of reducing maternal transfer of
      dioxins should also be investigated. Concentrations of 28 dioxin (polychlorinated
      dibenzo-p-dioxins, polychlorinated dibenzofurans, and co-planar polychlorinated
      biphenyls) congeners in blood, adipose tissue, breast milk, cord blood and
      placenta collected from 44 pregnant Japanese women were measured. In addition, to
      investigate potential reductions in maternal transfer of dioxins, 23 pregnant
      women were instructed to take Chlorella pyrenoidosa supplements during pregnancy.
      Correlations were observed between dioxin total toxic equivalents (total TEQ) in
      blood and total TEQ in adipose tissue (r=0.913, P<0.0001), breast milk (r=0.695,
      P=0.0007), and cord blood (r=0.759, P<0.0001). Dioxin levels transferred to
      fetuses and nursing infants reflect cumulative maternal concentrations of
      dioxins. A linear regression equation was introduced to predict total TEQ in
      breast milk and cord blood from dioxin levels in maternal blood, which should
      prove useful in evaluating fetal and infant risk of dioxin exposure. Total TEQ in
      cord blood were approximately 26% lower than in maternal blood (P<0.0001). The
      results of this study suggest that transplacental transfer differs depending on
      the dioxin congener. Total TEQ in breast milk were approximately 30% lower in the
      Chlorella group than in controls (P=0.0113). This finding suggests that maternal
      transfer of dioxins can be reduced using dietary measures such as Chlorella
      supplements.

PMID- 15985280
TI  - Enhanced dissipation of phenanthrene and pyrene in spiked soils by combined
      plants cultivation.
AB  - Polycyclic aromatic hydrocarbons (PAHs), a class of POPs, are widely distributed
      in the environment. Phytoremediation has long been recognized as a cost-effective
      method for removal of PAHs pollutants from soil. This study was conducted to
      investigate the capability of three plant species separately and their
      combination to promote the degradation of phenanthrene and pyrene in soil. The
      performance of three plant species, maize, ryegrass and white clover for
      phenanthrene and pyrene removal was also compared. The result showed that the
      presence of vegetation significantly enhances the dissipation of phenanthrene and
      pyrene in the soil environment. This effect was especially marked with maize. At
      the end of 60 days treatment, phenanthrene and pyrene concentrations in treated
      soils declined from an initial 52.52 mg kg-1 and 58.19 mg kg-1 to 4.15 mg kg-1
      and 6.77 mg kg-1, respectively, indicating that phenanthrene and pyrene was
      successfully removed by maize. Around 92.10% of phenanthrene and 88.36% of pyrene
      were removed from soils planted with maize. Within approximately two months
      experimental period, the dissipation extent showed that the 4-ring pyrene was
      more recalcitrant than 3-ring phenanthrene. Although the extents did not differ
      significantly among three tested species, the rates of degradation were
      different. The maize treatment had the highest rate of contaminant removal after
      two months, followed by white clover and annual ryegrass. As compare to single
      plant cultivation, combined plants cultivation significantly enhanced the
      destruction rate and extent of phenanthrene and pyrene in soils. Around 98.22% of
      phenanthrene and 95.81% of pyrene were removed from soils planted with maize and
      ryegrass. This research indicates the potential for phenanthrene and pyrene
      mineralization in combined plants cultivation, which may be especially useful for
      phytoremediation of soils contaminated with PAHs.

PMID- 15985281
TI  - Bioaerosol formation during grape stemming and crushing.
AB  - Indoor formation of airborne particles during pre-fermentation grape processing
      was assessed by particle counting using laser particle sizers. Particle numbers
      of four different aerodynamic size classes (0.3 to 0.5 microm, 0.5 to 1 microm, 1
      to 5 microm, and >5 microm) were determined during unloading of harvest
      containers and subsequent grape stemming and crushing. Regarding these size
      classes, composition before grape handling was determined as 87.9%, 10.4%, 1.7%,
      and 0.1%, respectively, whereas the composition changed during grape handling to
      50.4%, 15.2%, 33.0%, and 1.5%, respectively. Airborne bacteria and fungi
      originating from grape processing were collected by impactor and liquid impinger
      samplers. Grape handling resulted in a sixfold increase in total (biological and
      non-biological) airborne particles. The generation of bacterial and fungal
      aerosols was associated mostly with particles of aerodynamic diameters>5 microm
      (mainly 7 to 11 microm) as determined by flow cytometry. This fraction was
      increased 150fold in relation to background levels before grape crushing. Maximum
      concentrations of culturable bacteria reached 485,000 colony forming units
      (cfu/m3), whereas 146,000 cfu of fungi and yeasts were detected per cubic meter
      of air. Culturable Gram-negative bacteria occurred only in small numbers (180
      cfu/m3). In relation to the total number of airborne particles emitted,
      culturable microorganisms comprised 0.1% to 0.2%. As soon as grape crushing was
      stopped, particle concentrations decreased rapidly either due to passive settling
      or due to air currents in the occupational indoor environment reaching background
      levels.

PMID- 15985282
TI  - Using phosphate rock to immobilize metals in soil and increase arsenic uptake by
      hyperaccumulator Pteris vittata.
AB  - This greenhouse experiment evaluated the effects of phosphate rock (PR) on
      arsenic and metal uptake by the arsenic hyperaccumulator Pteris vittata in a soil
      spiked with arsenic and heavy metals Cd, Pb and Zn. Five soil treatments were
      used, 1) control with no arsenic, 2) spiked with 50 mg kg(-1) As (As) as Na2H
      AsO4, 3) spiked with 50 mg kg(-1) As and P as PR (AsP), 4) spiked with 50 mg kg(
      1) As, Pb, Cd, and Zn (AsM), and 5) spiked with 50 mg kg(-1) As, Pb, Cd, Zn and P
      (AsMP). The plants were harvested after growing in the soil for five weeks.
      Compared to the As treatment, the presence of heavy metals (AsM) reduced arsenic
      concentrations in the fronds from 1631 to 608 mg kg(-1). However, this effect was
      mitigated by PR (AsMP), with arsenic concentrations in the fronds increased from
      608 to 1046 mg kg(-1). Phosphate rock also significantly reduced Pb (13.5 to 4.10
      mg kg(-1)) and Cd (13.0 to 3.45 mg kg(-1)) concentrations in the fronds. Most of
      the arsenic in P. vittata was accumulated in the fronds (89-93%). Compared to the
      control, P was more concentrated in the roots along with less P being
      translocated to the fronds in the treatments with arsenic. While in those same
      treatments higher Ca concentrations in both the fronds and roots were observed.
      This research shows that PR was effective in increasing arsenic uptake and
      decreasing metal uptake by P. vittata and thus can be used as a cost-effective
      amendment for phytoremediation of arsenic and metal polluted soils.

PMID- 15985283
TI  - Characterization of large fleets of vehicle exhaust emissions in middle Taiwan by
      remote sensing.
AB  - Measurement of fleet emissions by means of remote sensing was conducted in middle
      Taiwan and the distributions and governing factors were characterized and
      examined. Results show the type of sampling sites is a dominant factor for the
      emission levels, and driving speeds and accelerations of the vehicles. In this
      study, the mean CO, HC, and NO concentrations at the urban and rural sites are
      apparently higher. The quantitative relationship between the pollutant
      concentration and mean speed or acceleration was established. Analysis of effect
      of the vehicle model year on the average fleet emissions was also conducted. It
      indicates those relatively older vehicles are higher emitters and contribute
      significantly more to total fleet emissions. On the other hand, the variation
      trends with model year are independent of the site characteristics and the effect
      of vehicle age on CO, HC, and NO emission is similar.

PMID- 15985284
TI  - Normal values for thrombelastography (ROTEM) and selected coagulation parameters
      in porcine blood.
AB  - The pig is a suitable animal model for researching blood coagulation and
      fibrinolysis. The present study therefore aimed to investigate in porcine blood
      the applicability of commercially available tests of coagulation and
      thrombelastography (ROTEM) and above all to determine normal values for
      coagulation parameters (e.g. prothrombin time (PT), activated partial
      thromboplastin time (aPTT), thrombin-antithrombin complexes (TAT), fibrinogen,
      antithrombin III (AT III), D-dimers, protein C). Except for the FibTEM and aPTT
      tests, all commercially available coagulation tests used were fully applicable
      for porcine blood. Normal values and reference intervals for porcine blood are
      given. As compared to the human reference intervals for the coagulation
      parameters investigated, porcine blood was found to be hypercoagulable.

PMID- 15985285
TI  - Influence of combined methylenetetrahydrofolate reductase (MTHFR) and thymidylate
      synthase enhancer region (TSER) polymorphisms to plasma homocysteine levels in
      Korean patients with recurrent spontaneous abortion.
AB  - OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) mutations known to be
      associated with hyperhomocysteinemia may be a risk factor for recurrent
      spontaneous abortion. Recently 28-bp tandem repeat polymorphism in thymidylate
      synthase enhancer region (TSER) was reported to affect plasma homocysteine level.
      We investigated the association between plasma homocysteine level and MTHFR and
      TSER genotypes. METHODS: Plasma homocysteine level was measured by fluorescent
      polarizing immunoassay. MTHFR mutations (C677T and A1298C) were identified by PCR
      restriction fragment length polymorphism assay. TSER mutation was analyzed by PCR
      method. RESULTS: Average homocysteine level was significantly higher in MTHFR
      677TT genotype (9.80+/-3.87 micromol/L) than in MTHFR 677CT (7.04+/-1.99
      micromol/L) in MTHFR 677CC genotype (8.14+/-1.74 micromol/L) in Korean patients
      with unexplained recurrent spontaneous abortion (p=0.0143). While MTHFR 1298AA
      showed the highest level, plasma homocysteine levels were not significantly
      different among MTHFR 1298AA (8.42+/-2.65 micromol/L), 1298AC (6.98+/-2.44
      micromol/L) and 1298CC (6.09+/-0.32 micromol/L) (p=0.2058). There was no
      significant difference among TSER genotypes (2R2R, 8.61+/-1.68 micromol/L; 2R3R,
      7.84+/-2.16 micromol/L; 3R3R, 8.05+/-2.81 micromol/L; p=0.9319). Among the
      combined genotypes of MTHFR C677T and TSER, 677TT-3R3R genotype had the highest
      homocysteine level (11.47+/-4.66 micromol/L). 1298AA-3R3R had the highest level
      (8.54+/-3.05 micromol/L) among the combined genotypes of MTHFR A1298C and TSER.
      CONCLUSION: Although there was no significant difference found among combined
      genotypes, 3R3R showed elevated homocysteine levels in MTHFR 677TT and 1298AA in
      Korean patients with unexplained recurrent spontaneous abortion. Thus TSER
      polymorphism may be a genetic determinant of plasma homocysteine level in Korean
      patients as well as MTHFR C677T polymorphism.

PMID- 15985287
TI  - The effect of 'tissue' and 'plasma' angiotensin converting enzyme inhibitors on
      overall haemostatic potentials in rats.

PMID- 15985286
TI  - Predictors of coronary artery disease in the Lebanese population.
AB  - BACKGROUND: Coronary artery disease (CAD) is one of the major causes of morbidity
      and mortality in the world. The disease is determined by many risk factors such
      as age, gender, diabetes, dyslipidemia, smoking, as well as elevated serum levels
      of lipoprotein (a) (Lp(a)), homocysteine, C-reactive protein (CRP) and uric acid.
      In this study, we evaluated the association of biologic and metabolic parameters
      with CAD in a group of Lebanese patients. METHODS: Three hundred patients were
      recruited for the study. Biologic and blood metabolic parameters were measured.
      Patients were then divided into 3 groups according to their catheterization
      result: 0% stenosis (controls), <50% stenosis and >or=50% stenosis. RESULTS:
      Hyperlipidemias, CRP, homocysteine and uric acid levels in CAD patients were not
      different from those of the controls. However, age, elevated fasting blood
      glucose (FBG) and elevated serum Lp(a) levels were found to be strong independent
      predictors of CAD in our study population. Association with CAD was also shown
      for gender, hypertension, diabetes and family history of CAD. CONCLUSION: We
      report the importance of serum Lp(a) levels and FBG in the prediction and
      prevention of CAD in our population.

PMID- 15985288
TI  - Treatment strategies for mares with placentitis.
AB  - Equine placentitis, and resultant preterm labor, are important sources of fetal
      and neonatal loss. The primary cause of equine placentitis is infection of the
      placenta with Streptococcus equi subspecies zooepidemicus, which ascends through
      the caudal reproductive tract. Current treatment protocols for mares affected
      with placentitis are empirical. This paper reviews treatment approaches for
      resolving placentitis and preterm labor in both equine and non-equine species.
      Specific therapies reviewed include antimicrobial, anti-inflammatory, tocolytic,
      and progestin agents.

PMID- 15985289
TI  - Update on equine ICSI and cloning.
AB  - Intracytoplasmic sperm injection (ICSI) has recently become efficient enough to
      be considered for clinical use. With ICSI, one spermatozoa is injected into a
      mature oocyte. Harvesting of an oocyte ex vivo, followed by ICSI and transfer of
      the fertilized oocyte to the oviduct, may be applicable when semen quality is
      insufficient for standard insemination. Sperm injection, followed by in vitro
      embryo culture to the blastocyst stage, may be used in cases where multiple
      oocytes are to be fertilized (e.g. when oocytes are collected post-mortem).
      Nuclear transfer (cloning) of horses is possible but still inefficient; however,
      commercial companies currently will culture and store cells from privately owned
      animals for a reasonable fee. Horse owners are beginning to realize the potential
      of cloning for salvaging valuable equine genetics that may otherwise be lost.

PMID- 15985290
TI  - In vitro development and post-thaw survival of blastocysts derived from
      delipidated zygotes from domestic cats.
AB  - The ability to cryopreserve in vitro-produced feline embryos was investigated. To
      improve the survival rate of cryopreserved embryos, first the developmental
      ability of in vitro fertilized feline zygotes (after removal of intracellular
      lipids) was determined, followed by the post-thaw survival of cryopreserved
      blastocysts derived from delipidated zygotes. More than 67% of the delipidated
      zygotes cleaved and 36% of them developed to the morula stage. The developmental
      ability of delipidated zygotes to the blastocyst stage (26%) was similar to that
      of sham-operated (30.5%) or control embryos (31.3%). Although the survival rate
      of delipidated blastocysts (81.8%) after freezing and thawing tended to be higher
      than that of control embryos without delipidation (60.6%), rates were not
      significantly different between the both groups. In conclusion, in vitro-produced
      feline blastocysts were successfully frozen, removal of the cytoplasmic lipid
      content in feline zygotes did not impair their in vitro developmental competence
      (up to the blastocyst stage), and reduction of cytoplasmic lipids by aspiration
      had no apparent effects on the survival of in vitro-derived blastocysts after
      cryopreservation.

PMID- 15985291
TI  - Step-size of net filament sliding of muscle contraction.
AB  - The step-size defined as the movement between actin and myosin filaments per ATP
      split is an important issue in the research of muscle contraction. According to
      the conventional swinging-cross-bridge theory by Huxley, the step-size in this
      sense should be within 40 nm, a maximum possible stroke size of a myosin head, 20
      nm, swing through an arc of 180 degrees . Since 1996, the estimated value over 40
      nm has not been reported. Recently, however, there have been several discussions
      based on the one of the smallest values of step-size, 1.7 nm. We carefully re
      evaluated the estimation process for the step-size, concluding that the values
      are still limited within 10-20 nm of conventional swinging-cross-bridge theory:
      12.6 nm at no load for frog muscle.

PMID- 15985292
TI  - In vitro cartilage tissue engineering with 3D porous aqueous-derived silk
      scaffolds and mesenchymal stem cells.
AB  - Adult cartilage tissue has limited self-repair capacity, especially in the case
      of severe damages caused by developmental abnormalities, trauma, or aging-related
      degeneration like osteoarthritis. Adult mesenchymal stem cells (MSCs) have the
      potential to differentiate into cells of different lineages including bone,
      cartilage, and fat. In vitro cartilage tissue engineering using autologous MSCs
      and three-dimensional (3-D) porous scaffolds has the potential for the successful
      repair of severe cartilage damage. Ideally, scaffolds designed for cartilage
      tissue engineering should have optimal structural and mechanical properties,
      excellent biocompatibility, controlled degradation rate, and good handling
      characteristics. In the present work, a novel, highly porous silk scaffold was
      developed by an aqueous process according to these criteria and subsequently
      combined with MSCs for in vitro cartilage tissue engineering. Chondrogenesis of
      MSCs in the silk scaffold was evident by real-time RT-PCR analysis for cartilage
      specific ECM gene markers, histological and immunohistochemical evaluations of
      cartilage-specific ECM components. Dexamethasone and TGF-beta3 were essential for
      the survival, proliferation and chondrogenesis of MSCs in the silk scaffolds. The
      attachment, proliferation, and differentiation of MSCs in the silk scaffold
      showed unique characteristics. After 3 weeks of cultivation, the spatial cell
      arrangement and the collagen type-II distribution in the MSCs-silk scaffold
      constructs resembles those in native articular cartilage tissue, suggesting
      promise for these novel 3-D degradable silk-based scaffolds in MSC-based
      cartilage repair. Further in vivo evaluation is necessary to fully recognize the
      clinical relevance of these observations.

PMID- 15985293
TI  - More than one type of transglutaminase in invertebrates? A second type of
      transglutaminase is involved in shrimp coagulation.
AB  - Coagulation (clot formation) forms a physical barrier to prevent the loss of body
      fluid and dissemination of microbes into the haemocoel after injury or infection.
      Its quickness and efficiency are essential for the survival of invertebrates that
      rely solely on innate immunity. Transglutaminase (TG) catalyses intermolecular or
      intramolecular epsilon-(gamma-glutamyl) lysine bond formation, resulting in a
      protein polymerisation, and plays a role in blood coagulation and post
      translational protein remodelling. In the present study, we cloned a TG from
      shrimp (Penaeus monodon) haemocyte cDNA. It was assigned as shrimp
      transglutaminase II (STG II). The STG II cDNA consists of a coding region of
      2,274bp. The deduced protein has 757 amino acid residues with a calculated
      molecular mass of 85,000 Da and an isoelectric point of 5.48. RT-PCR results
      showed a significant level of STG II expression in haemocytes but not in
      hepatopancreas, in contrast to shrimp STG I (AY074924.1). The genetic distance
      between STG II and STG I is much larger than the distance between STG II and the
      TG of the kuruma shrimp (Marsupenaeus japonicus). Evidence based on tissue
      distribution and genetic distance suggests that no less than two types of shrimp
      TG exist that are encoded at different chromosomal locations. The recombinant STG
      II (rSTG II) incorporated a TG-specific substrate, dansylcadaverine (DCA), into
      clottable proteins (CP) in a calcium dependent manner. Other haemocyte- or plasma
      derived TG substrate is not required for CP polymerisation but may be necessary
      for stable clot formation. The rSTG II catalysed clottable proteins into a long
      chain under transmission electron microscopy (TEM) observation. In conclusion,
      STG II is characterized as a haemocyte TG and is involved in coagulation.

PMID- 15985294
TI  - An improved method for determination of gene copy numbers in transgenic mice by
      serial dilution curves obtained by real-time quantitative PCR assay.
AB  - Precise characterization of transgene insertion is necessary for phenotype
      interpretation of transgenic animals. To check for the presence of deletions,
      estimate the number of inserted transgene copies, and in addition, identify the
      zygosity of transgenic mice, gene copy numbers were determined by real-time
      quantitative PCR. Instead of correlating tested samples to a single relative
      standard curve, serial dilution curves were constructed for every mouse sample. A
      novel statistical approach was designed in which mice with the same copy number
      were characterized by the adjusted group mean and standard deviation common to
      the target sequence. This enabled us to characterize the variability of the
      obtained results, statistically compare different groups of mice and estimate
      precision and limits of the applied method.

PMID- 15985295
TI  - Topiramate in treatment of depressive and anger symptoms in female depressive
      patients: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Depression is associated with increased aggression and diminished
      ability and quality of life. The goal of this study was to compare the efficacy
      of topiramate in influencing depressive symptoms, aggression, ability, and health
      related quality of life in depressive women. METHODS: We conducted a randomized,
      double-blind, placebo-controlled 10-week study of topiramate in 64 female
      subjects from the general population who met criteria for recurrent major
      depressive disorder. Primary outcome measures were changes on the Hamilton
      Depression Rating Scale (HDRS), the State-Trait Anger Expression Inventory
      (STAXI), the Test of Attention (d2), and the SF-36 Health Survey (SF-36).
      RESULTS: According to the intent-to-treat principle, a significant difference on
      the HDRS (P=0.02), all scales of STAXI (all P<0.001), Total efficiency of d2
      (P<0.001), and on most scales of SF-36 (P between 0.15 and <0.001) were observed
      in the topiramate-treated subjects comprised the placebo group. The reduction in
      expression of anger correlated significantly with changes on the HDRS, and
      several scales of d2 and SF-36. Additional weight loss, which was significantly
      more pronounced in the topiramate group than in those treated with a placebo, was
      ascertained (difference in weight loss between the two groups: 4.2 kg, P<0.001).
      All the patients tolerated topiramate relatively well. LIMITATIONS: Only
      moderately ill women were included. CONCLUSIONS: Topiramate appears to be an
      effective agent in the reduction of depressive symptoms and anger and in the
      improvement of ability and health-related quality of life in depressive women.
      Additional weight loss can be expected.

PMID- 15985296
TI  - Accidental childhood strangulation by human hair.
AB  - A low-income mother is accused of child abuse after co-sleeping with, and then
      waking to find her 13-month-old daughter entangled and apparently strangling in
      the mother's hair. The baby was initially unconscious and cyanotic; revived by
      the time the parents reached the ER, clinical examination revealed a ligature
      mark on the neck and petechiae on the face. In a pro bono effort, her attorney
      teamed with RAM Consulting as an expert witness. RAM performed a six-part
      investigation including: (1) an anthropometric analysis, (2) determination of the
      strength of human hair, (3) characterization of the ligature mark, (4) an
      investigation into airway occlusion forces, (5) an investigation into the
      conditions required to initiate petechiae, and (6) a review of the literature.
      Our conclusion was that it is possible for a strangulation incident to occur when
      a young child is co-sleeping with a parent with long hair, and that this scenario
      may result in injury or death. Upon review of this report and RAM's deposition on
      this matter, the prosecuting attorney's expert witness withdrew her testimony and
      the judge dismissed the case.

PMID- 15985297
TI  - Pneumolabyrinth following traumatic luxation of the stapes into the vestibule.
AB  - Pneumolabyrinth can result from traumatic luxation of stapes into the vestibule.
      The diagnosis of stapes luxation following a head injury can be delayed
      especially if the otoscopic examination is within normal limits. Here a 15-year
      old girl presenting with vertigo and nystagmus following a blunt head injury was
      presented, whose computerized tomography revealed air in the vestibule and
      cochlea (pneumolabyrinth) and stapes was found to be luxated into the vestibule.

PMID- 15985298
TI  - Pediatric facial nerve paralysis: patients, management and outcomes.
AB  - OBJECTIVE: To characterize the causes and treatment of facial nerve paresis (FNP)
      in pediatric patients. METHOD: Retrospective study in a tertiary care pediatric
      hospital. Thirty-four patients identified with partial or complete FNP evaluated
      between 1997 and 2003. A review of the medical records including sex, age,
      laterality, etiology, therapy, severity of paralysis according to House-Brackman
      (HB) six-point grading scale, duration, and degree of recovery. RESULTS: Thirty
      five cases of FNP. Causes of FNP were infectious (13), traumatic (7), iatrogenic
      (5), congenital (4), Bell's/Idiopathic (3), relapsing (2) and neoplastic (1).
      Peak age distributions for both infectious and traumatic etiologies were bimodal:
      1-3 and 8-12 years. Of the 13 infectious cases, 11 were associated with acute
      otitis media with effusion (AOME). Four (4/11) were bacterial-culture negative.
      Seven (7/11) were bacterial-culture positive, four (4/7) of which required
      prolonged, broth-medium culture. Bacteria cultured predominantly included
      Staphylococcus non-aureus species (5/7) and Propionobacterium acnes (3/7). One
      (1/13) was viral culture positive (Herpes Simplex Virus). All six patients who
      received intravenous steroids for OME-associated FNP received the doses within
      the first week of presentation and had complete recovery (HB I/VI); three of five
      patients who did not receive steroids had complete recovery. There were five
      iatrogenic cases; two (2/5) were planned surgical sacrifices and three (3/5) were
      complications of middle ear/mastoid surgery. Facial nerve function associated
      with infection returned in 0.5-2 months while, when associated with trauma,
      returned in 0.25-30 months. CONCLUSIONS: In infectious or traumatic FNP, children
      aged 1-3 and 8-12 years are the primary groups involved. In AOME FNP, culture
      identified organisms may not be representative of traditional pathogens.
      Infectious FNP averaged 1 month for recovery while traumatic FNP averaged 9
      months. Intravenous steroid therapy may improve the outcome. Recovery was
      complete (HB I/VI) in 8/10 infectious and 4/6 traumatic cases.

PMID- 15985299
TI  - Nocturia and the burning mouth syndrome (BMS) in the elderly.
AB  - The aim of this study was to assess the relationship between BMS and nocturnal
      micturition in a group of elderly men and women. The study comprised 6103 elderly
      men and women recruited from a group of pensioners by means of a questionnaire
      (n=10,216; response rate 61.3%). The mean (+/-S.D.) ages of the men and women
      were 73.0+/-6.0 years and 72.6+/-6.7 years, respectively. The questionnaire
      included questions on their health, diseases and symptoms, drugs, sleep habits
      and the number of nocturnal voiding episodes. BMS was reported by 2.4% of the men
      and 8.5% of the women (p<0.0001). The occurrence of BMS was unaffected by age in
      both sexes. In women, but not in men, there was a stepwise increase in BMS in
      parallel with increased nocturnal micturition. There was a strong relation
      between nocturnal thirst and drinking on the one hand, and reports on BMS on the
      other hand. BMS was also increased in diuretics users in both sexes. The results
      may indicate that negative fluid balance as a consequence of nocturnal polyuria
      is an overlooked pathogenetic mechanism in the genesis of BMS in the elderly.

PMID- 15985300
TI  - Discrete subaortic stenosis after the correction of atrioventricular septal
      defect in an adult.

PMID- 15985301
TI  - C-reactive protein and atrial fibrillation: "evidence for the presence of
      inflammation in the perpetuation of the arrhythmia".
AB  - BACKGROUND: Atrial fibrillation (AF) is associated to a high risk of systemic
      embolism. The mechanisms that contribute to thrombogenesis in these patients are
      still poorly understood. Systemic and/or local inflammation could be involved in
      the process of thrombogenesis and contribute to the perpetuation of the
      arrhythmia. The purpose of the study was to evaluate the role of inflammation and
      its relation to thrombogenesis and cardiac rhythm in AF. METHODS: We
      prospectively studied 130 patients with newly diagnosed non-valvular AF in
      absence of antithrombotic therapy. Determinations of C-reactive protein (CRP) and
      thrombin-antithrombin complex (TAT) plasma levels, along with a transesophageal
      echocardiogram were performed in all the patients at admission. RESULTS: Mean age
      of the group was 67+/-14 years. CRP levels were significantly elevated in AF
      patients versus controls (matched by age, gender and cardiovascular risk factors)
      (1.0+/-1.8 versus 0.3+/-0.4 mg/dl, respectively, p<0.01). Baseline TAT levels
      were also significantly elevated in AF patients but no correlation was found
      between CRP and TAT. At 1-year of follow-up, mean CRP levels were still elevated
      in patients that remained in AF compared to those who converted to sinus rhythm
      (1.2+/-1.8 compared to 0.5+/-1.5 mg/dl, p=0.03). CRP was the only biochemical
      predictor of sinus rhythm maintenance at 1-year follow-up independently of
      clinical (including adjustment for risk factors and antiarrhythmic drugs),
      biochemical and echo parameters. CONCLUSIONS: There is evidence for the presence
      of inflammation in patients with non-valvular AF, which is not related to
      activation of the coagulation cascade. The persistence of inflammation is
      associated with chronic AF at 1-year follow up.

PMID- 15985302
TI  - Sustained torsade de pointes occurring early during oral sotalol therapy for
      atrial fibrillation recurrence prophylaxis in a patient without heart disease.
AB  - This report describes a 64 year-old female patient admitted to our department for
      recurrent and symptomatic episodes of atrial fibrillation. Antiarrhythmic therapy
      with sotalol at 240 mg/day was started, and after 48 h the patient experienced
      several episodes of sustained torsade de pointes, dramatic marked QT interval
      prolongation and negative T wave, in absence of overt cardiac disease, renal
      failure, electrolyte abnormalities or baseline QT interval prolongation. This
      case emphasizes the importance of hospitalization at the starting of sotalol
      therapy, especially in female patients, even in absence of predisposing factors
      for drug-induced tachyarrhythmias.

PMID- 15985303
TI  - Risk factors for digital dermatitis in dairy cows kept in cubicle houses in The
      Netherlands.
AB  - The presence of digital dermatitis (DD) in dairy cows has increased considerably
      over the last 10 years in The Netherlands, resulting in a current prevalence of
      approximately 30% in cows kept in cubicle houses. Our objective was to evaluate a
      diversified sample of cow- and herd-related risk factors for DD in dairy cows
      housed in cubicle houses with different flooring systems. Associations were
      analysed in random-effects logistic-regression models using 2,134 cows (37 herds)
      and 2,892 cows (47 herds) in the pasture and housing studies, respectively. At
      cow-level, the odds of having DD were increased in the case of lower parity and
      lactation. Important risk factors at herd-level were: restricted grazing time,
      fast rise in concentrate amount after calving, feeding by-products, herd trimming
      only at long intervals, and introduction of dry cows into the lactating herd
      before calving. The odds for DD were lower if cows were housed on a slatted floor
      with manure scraper and provided long and wide cubicles, and if calves were
      reared in the dairy cows' accommodation.

PMID- 15985304
TI  - Comparison of three methods for detecting Campylobacter spp. in chilled or frozen
      meat.
AB  - There is a demand from the meat industry as well as from public health
      authorities for a simple and rapid detection method for thermophilic
      Campylobacter spp. from food. Hence, we compared different isolation procedures
      for their usefulness for this purpose. Bolton enrichment medium without blood,
      incubated statically in stomacher bags in microaerophilic atmosphere, detected
      more samples positive for thermophilic Campylobacter spp. than did Preston
      enrichment broth in bottles with small headspace and tight caps, incubated in
      aerobic atmosphere. Use of an automated antigen detection system to identify
      enrichment cultures positive for Campylobacter spp. was as sensitive as selective
      agars, and reduced the detection time by 24 h. Campylobacter spp. were recovered
      from 18.4% of the 461 samples tested. The prevalence was highest in refrigerated
      poultry meat (52% of the 80 samples tested) and poultry offal (41% of the 44
      samples tested).

PMID- 15985305
TI  - Production of beta-galactosidase by Bifidobacteria as influenced by various
      culture conditions.
AB  - Beta-Galactosidase production by Bifidobacterium longum CCRC 15708,
      Bifidobacterium longum B6 and Bifidobacterium infantis CCRC 14633 was first
      examined with B. longum CCRC 15708 showing the highest production of beta
      galactosidase and the highest specific activity. Further study with B. longum
      CCRC 15708 revealed that the highest level of beta-galactosidase was produced
      with lactose and yeast extract as carbon and nitrogen sources, respectively.
      Optimal enzyme production occurred at an initial pH of 6.5 and at 37 degrees C.
      Under these optimum culture conditions, a maximumbeta-galactosidase activity of
      18.6 U/ml could be obtained after 16 h of fermentation in a medium contain 4%
      lactose, 3.5% yeast extract, 0.3% K2HPO4, 0.1% KH2PO4, 0.05% MgSO4.7H2O and 0.03%
      L-cysteine. The highest transgalactosylation activity was also detected in this
      culture after 14-16 h of fermentation.

PMID- 15985306
TI  - Benefit in lung function improvement and side-effect profile of long-term
      responders: an analysis of 14 NSCLC patients treated for at least 9 months with
      gefitinib.
AB  - BACKGROUND: Gefitinib is the first approved EGFR tyrosine-kinase inhibitor
      indicated for the treatment of patients with locally advanced (IIIB) or
      metastatic NSCLC after failure of platinum-based first-line therapy and docetaxel
      chemotherapy. Following rapid approval in Japan and accelerated approval based on
      phase-II results in the US, a large compassionate-use program has been set up in
      parallel to extended phase-III testing. Offering therefore access to state-of-the
      art therapy to patients who are not candidates for clinical studies; Iressatrade
      mark EAP allows physicians to test the new EGFR inhibitor across a heterogeneous
      patient population characteristic for advanced NSCLC. PATIENT AND METHODS: After
      having treated 240 patients at the Grosshansdorf hospital, we have
      retrospectively analysed the efficacy and tolerability of 250 mg/day gefitinib in
      patients showing a long-term tumor control. We reviewed the patient records of 14
      patients with advanced NSCLC that received daily gefitinib for at least 9 months.
      RESULTS: Long-term tumor control, defined as confirmed objective tumor response
      for at least 6 months or disease stabilisation for above 9 months, was observed
      in chemo-naive patients as well as in fourth-line therapy patients for the latter
      ones independently of the composition of prior chemotherapy. Most patients (9/14)
      with such a lasting benefit were female; patients' histology was in most cases
      uniform: adenocarcinomas were dominant in women and bronchioloalveolar carcinoma
      in men. Patients with moderate to severe dyspnoea benefited from a measurable
      improvement of their respiratory capacity. No cumulative toxicity was observed;
      characteristic side-effects for gefitinib as grades 1-2 diarrhoea or mild to
      moderate skin toxicity were well manageable. CONCLUSION: For 14 (6%) out of 240
      patients with patterns of diffuse disseminated metastatic disease, gefitinib
      offered a lasting tumor control with a disease progression-free survival interval
      between 9 and 25 months. In parallel to therapy, patients' performance status
      (PS) could be conserved or even improved in many cases. Patients with lung
      function impairment, as well as patients with other disease-related symptoms
      obtained additional therapy benefits.

PMID- 15985307
TI  - Role of gamma-MSH peptides in the regulation of adrenal steroidogenesis.
AB  - Alpha-, beta- and gamma-melanocyte stimulating hormones (MSHs) are peptides
      derived from the ACTH precursor, pro-opiomelanocortin. All three peptides have
      been highly conserved throughout evolution but their exact biological function in
      mammals is still largely obscure. In recent years, there has been a surge of
      interest in alpha-MSH and its role in the regulation of feeding. Gamma-MSH by
      contrast has been shown to be involved in the regulation of adrenal
      steroidogenesis and also has effects on the cardiovascular and renal systems.
      This review will provide an overview of the role that gamma-MSH peptides play in
      the regulation of adrenal steroidogenesis.

PMID- 15985308
TI  - N-alkylated dipeptide amides and related structures as imitations of the
      melanocortins' active core.
AB  - Thirty-three low molecular mass structures combining both peptide and peptoid
      features were prepared and tested on human melanocortin receptors MC1,3-5R. Most
      of them displayed low micromolar activity with preference for diamines, guanidino
      and 2-naphthyl derivatives compared to monoacetylated, amino and 3-indolyl
      counterparts. Some contained L- or D-histidine residues, but the change did not
      influence affinity. QSAR modelling yielded excellent models for the MC3-5
      receptors explaining R2Y=0.89-0.91 and predicting Q2=0.77-0.80 of the affinity
      variations. One compound displayed MC1R selectivity (13-fold and more). An NMR
      study of showed that it exists as a mixture of four rotamers at its tertiary
      amide bonds. Comparisons with earlier data for melanocortin core tetrapeptide
      analogues indicate that the novel peptide-peptoids interact with the melanocortin
      receptors in a different way.

PMID- 15985309
TI  - Rattus norvegicus melanocortin 3 receptor: a corrected sequence.
AB  - Examination of the Rattus norvegicus genome reveals differences in the
      melanocortin 3 receptor (MC3R) compared with the published sequence (accession
      X70667). To clarify these differences, we used RT-PCR to clone MC3R from Sprague
      Dawley rats. These efforts revealed a sequence for the rat MC3R consistent with
      that predicted by the rat genome, but different from the published receptor by
      three amino acids, all of which were located in the predicted second
      transmembrane domain (TM2). Analysis of these residues revealed that TM2 of the
      rat MC3R is more homologous with other species than previously considered. The
      presently described sequence maps onto chromosome 3 of the rat genome, which
      shows highly conserved synteny with the mouse chromosome 2 and the human
      chromosome 20. Transient expression revealed high affinity binding of [125I]-NDP
      MSH and a concentration-dependent cAMP response to the synthetic agonist MTII.
      These data both clarify the sequence of the MC3R and demonstrate the great
      utility of genomic information recently made available.

PMID- 15985310
TI  - Evolutionary conservation of the structural, pharmacological, and genomic
      characteristics of the melanocortin receptor subtypes.
AB  - We have cloned melanocortin receptors (MCRs) from several species of fish. The
      MC4R and MC5R subtypes arose early in vertebrate evolution and their primary
      structure is remarkably conserved. Expression and pharmacological
      characterization of the MCRs in fish has revealed that they bind and respond to
      melanocortin peptides with high potency. Detailed characterization of the binding
      properties of the different subtypes suggests that MCRs in early vertebrates had
      preference for adrenocorticotropic hormone (ACTH) peptides, while the high
      sensitivity for the shorter proopiomelanocortin (POMC) products, such as the
      alpha-, beta-, and gamma-melanocyte-stimulating hormone (MSH), has appeared
      later, perhaps as the MCR subtypes gained more specialized functions. The MCR
      repertoire shows in general high similarities in their primary structures, while
      they are however not similar in terms of functional roles. The MCRs serve
      therefore as an interesting model family to understand the molecular mechanisms
      of how functions of the genes can diverge during evolution. In this review, we
      provide an overview of our recent studies on the cloning, expression,
      pharmacology, 3D modeling, and genomic studies of the MCRs in non-mammalian
      species.

PMID- 15985311
TI  - Potent peptide agonists for human melanocortin 3 and 4 receptors derived from
      enzymatic cleavages of human beta-MSH(5-22) by dipeptidyl peptidase I and
      dipeptidyl peptidase IV.
AB  - Human beta-MSH(1-22) was first isolated from human pituitary as a 22-amino acid
      (aa) peptide derived from a precursor protein, pro-opiomelanocortin (POMC).
      However, Bertagna et al. demonstrated that a shorter human beta-MSH(5-22),
      (DEGPYRMEHFRWGSPPKD), is a true endogenous peptide produced in human
      hypothalamus. In this report, we demonstrated that in vitro enzymatic cleavage of
      native human beta-MSH(5-22) with two ubiquitous dipeptidyl peptidases (DPP), DPP
      I and DPP-IV, generated two potent MC3/4R peptide analogues, beta-MSH(7-22)
      (GPYRMEHFRWGSPPKD) and beta-MSH(9-22) (YRMEHFRWGSPPKD). In fact, the MC4R binding
      affinity and functional potency of beta-MSH(7-22) (Ki=4.6 nM, EC50=0.6 nM) and
      beta-MSH(9-22) (Ki=5.7 nM, EC50=0.6 nM) are almost an order of magnitude greater
      than those of their parent peptide, beta-MSH(5-22) (MC4R, Ki=23 nM, EC50= 3nM).
      Furthermore, the DPP-I/DPP-IV cleaved peptide, beta-MSH(9-22), when administered
      intracerebroventricularly (ICV) at a dose of 3 nmol/rat, potently induced an
      acute negative energy balance in a diet-induced obese rat model, while its parent
      molecule, beta-MSH(5-22), administered at the same dose did not have any effect.
      These data suggest that DPP-I and DPP-IV may play a role in converting the
      endogenous beta-MSH(5-22) to more potent peptides that regulate energy
      homeostasis in the hypothalamus.

PMID- 15985312
TI  - Pentylenetetrazol-induced seizures affect the levels of prolyl oligopeptidase,
      thimet oligopeptidase and glial proteins in rat brain regions, and attenuation by
      MK-801 pretreatment.
AB  - The regulatory mechanisms of neuropeptide-metabolizing enzymes often play a
      critical role in the pathogenesis of neuronal damage. A systemic administration
      of pentylenetetrazol (PTZ), an antagonist of GABA(A) receptor ion channel binding
      site, causes generalized epilepsy in an animal model. In the present study, we
      examined the involvement of prolyl oligopeptidase (POP), thimet
      oligopeptidase/neurolysin (EP 24.15/16) and glial proteins in PTZ-treated rat
      brain regions, and the suppressive effect of MK-801, a non-competitive NMDA
      receptor antagonist, pretreatment for their proteins. The activity of POP
      significantly decreased in the hippocampus at 30min and 3h, and in the frontal
      cortex at 3h after PTZ treatment, and pretreatment with MK-801 recovered the
      activity in the cortex at 3h. The activity of EP 24.15/16 significantly decreased
      in the hippocampus at 3h and 1 day, and in the cortex at 3h after the PTZ
      administration, whereas pretreatment with MK-801 recovered the change of the
      activity. The Western blot analysis of EP 24.15 showed significant decrease of
      the protein level in the hippocampus 3h after the PTZ treatment, whereas
      pretreatment with MK-801 recovered. The expression of GFAP and CD11b
      immunohistochemically increased in the hippocampus of the PTZ-treated rat as
      compared with controls. Pretreatment with MK-801 also recovered the GFAP and
      CD11b expression. These data suggest that PTZ-induced seizures of the rats cause
      indirect activation of glutamate NMDA receptors, then decrease POP and EP
      24.15/16 enzyme activities and EP 24.15 immunoreactivity in the neuronal cells of
      the hippocampal formation. We speculate that changes of those peptidases in the
      brain may be related to the levels of the neuropeptides regulating PTZ-induced
      seizures.

PMID- 15985313
TI  - Changes in expression of neuronal and glial glutamate transporters in lead
      exposed adult rat brain.
AB  - Excitatory amino acid transporters (EAATs) are membrane-bound proteins localized
      in glial and neuronal cells which transport glutamate (Glu) in a process
      essential for terminating its action and protecting neurons from excitotoxic
      damage. Since Pb-induced neurotoxicity has a glutamatergic component and
      astrocytes serve as a cellular Pb deposition site, it was of interest to
      investigate the response of main glutamate transporters to short-term lead
      exposure in the adult rat brain (25mg/kg b.w. of lead acetate, i.p. for 3 days).
      We examined the expression of mRNA and protein of GLAST, GLT-1 and EAAC1 in
      homogenates obtained from cerebellum, hippocampus and forebrain. Molecular
      evidence is provided which indicates that, of the two glial transporters, GLT-1
      is more susceptible than GLAST to the neurotoxic effect arising from Pb. RT-PCR
      analysis revealed highly decreased expression of GLT-1 mRNA in forebrain and
      hippocampus. In contrast, GLAST was overexpressed in forebrain and in cerebellum.
      In the case of EAAC1, the enhanced expression of mRNA and protein of transporter
      was observed only in forebrain. The results demonstrate regional differences in
      the expression of glutamate transporters after short-term exposure to Pb. In
      forebrain, downregulation of GLT-1 is compensated by enhanced expression of
      GLAST, while in hippocampus, the expression of both is lowered. This observation
      suggests that under conditions of Pb toxicity in adult rat brain, the hippocampus
      is most vulnerable to the excitotoxic cell damage arising from impaired clearance
      of the released glutamate.

PMID- 15985314
TI  - Revealing the role of glutathione S-transferase omega in age-at-onset of
      Alzheimer and Parkinson diseases.
AB  - We previously reported a linkage region on chromosome 10q for age-at-onset (AAO)
      of Alzheimer (AD) and Parkinson (PD) diseases. Glutathione S-transferase, omega-1
      (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then
      reported to associate with AAO of AD and PD. To examine whether GSTO1 and GSTO2
      (hereafter referred to as GSTO1h) are responsible for the linkage evidence, we
      identified 39 families in AD that lead to our previous linkage and association
      findings. The evidence of linkage and association was markedly diminished after
      removing these 39 families from the analyses, thus providing support that GSTO1h
      drives the original linkage results. The maximum average AAO delayed by GSTO1h
      SNP 7-1 (rs4825, A nucleotide) was 6.8 (+/-4.41) years for AD and 8.6(+/-5.71)
      for PD, respectively. This is comparable to the magnitude of AAO difference by
      APOE-4 in these same AD and PD families. These findings suggest the presence of
      genetic heterogeneity for GSTO1h's effect on AAO, and support GSTO1h's role in
      modifying AAO in these two disorders.

PMID- 15985315
TI  - No definitive evidence for L-Zagreb mumps strain associated aseptic meningitis: a
      review with special reference to the da Cunha study.
AB  - The study by da Cunha et al. published in 2002 reported that MMR vaccine
      containing L-Zagreb mumps strain manufactured by Serum Institute of India Ltd.
      caused a high incidence of aseptic meningitis (AM) from routine surveillance
      during two mass immunization campaigns (MIC) conducted in 1998 in two states in
      Brazil. Since the results were contrary to those in India, Egypt and Bahamas, a
      critical analysis of the study was done. Several inconsistencies were found in
      the study, which undermined the conclusions drawn. Two similar studies from
      Brazil reported similar results. Review of these studies and those done on the
      vaccine from Zagreb, Croatia showed that in no study the L-Zagreb mumps virus has
      been isolated from cerebrospinal fluid (CSF) of an AM case. Isolation of the
      vaccine virus is necessary for definite causal association of AM with the
      vaccine. There is no such evidence to causally link MMR vaccine containing L
      Zagreb mumps strain with AM.

PMID- 15985316
TI  - Induction of CD8+ T cell responses by Yersinia vaccine carrier strains.
AB  - Yersinia enterocolitica employs a type III secretion system (TTSS) to target
      virulence factors (e.g. YopE) into the cytosol of the host cells. We utilized the
      TTSS to introduce a recombinant antigen directly into the cytosol of host cells
      and to investigate the potential of Y. enterocolitica and Y. pseudotuberculosis
      as live carrier for vaccines. The model antigen ovalbumin (Ova) was fused to
      defined secretion or translocation domains of the Yersinia effector protein YopE
      and introduced into attenuated mutant strains of Y. enterocolitica and Y.
      pseudotuberculosis. In vitro experiments showed secretion and translocation of
      YopE-Ova hybrid proteins into host cells. To investigate the resulting immune
      responses, mice expressing transgenic Ova-specific T cell receptors were used.
      Both Y. enterocolitica and Y. pseudotuberculosis mutants induced efficaciously
      Ova-specific CD8+ T cell responses. The translocation domain of YopE was required
      for induction of CD8+ T cell responses in vivo, but not for T cell responses
      induced in vitro. The in vivo frequency of Ova-specific splenic T cells was up to
      six-fold higher in mice immunized with YopE-Ova-translocating Y.
      enterocolitica/Y. pseudotuberculosis mutants than in control mice. The Ova
      specific T cells were shown to produce high amounts of IFN-gamma. We did not
      observe significant Ova-specific CD4+ T cell or antibody responses upon
      vaccination with either of the strains. In conclusion, Yersinia live carrier
      vaccine strains are suitable to target antigens into the MHC class I pathway and
      stimulate CD8+ T cell responses and thus, might be useful in vaccine approaches
      against intracellular pathogens.

PMID- 15985317
TI  - Mucosally-administered human-simian immunodeficiency virus DNA and fowlpoxvirus
      based recombinant vaccines reduce acute phase viral replication in macaques
      following vaginal challenge with CCR5-tropic SHIVSF162P3.
AB  - Further advances are required in understanding protection from AIDS by T cell
      immunity across mucosal sites of virus transmission. We analysed a set of
      multigenic HIV and SHIV DNA and Fowlpoxvirus (FPV) prime and boost vaccines for
      immunogenicity and protective efficacy in outbred pigtail macaques when delivered
      via mucosal surfaces (intranasally or intrarectally). Intranasally delivered DNA,
      even when adjuvanted and given as a fine droplet spray, was neither immunogenic
      nor protective in macaques. Some protection from acute infection with a
      pathogenic vaginal SHIVSF162P3 challenge was, however, observed with a regimen
      involving intramuscular DNA vaccine priming followed by either intranasally or
      intrarectally delivered rFPV boosting. Interestingly, animals boosted with rFPV
      vaccine via either of these mucosal routes had poor circulating T cell responses
      prior to challenge with SHIV compared to those boosted via the intramuscular
      route. Nevertheless, the mucosally-vaccinated animals generated equivalent
      anamnestic mucosal and systemic SHIV-specific CD4 and CD8 T cell responses
      following SHIV administration, with significant reduction in acute plasma viremia
      against this vaginal challenge. Our data suggest strategies for effective priming
      of partial immunity to mucosal HIV-1 exposure utilizing systemic prime and
      mucosal boost vaccination strategies.

PMID- 15985318
TI  - Clinical safety and efficacy of a powdered Hepatitis B nucleic acid vaccine
      delivered to the epidermis by a commercial prototype device.
AB  - This clinical delivery system bridging study evaluated the performance of a
      single-use disposable, commercial prototype device (designated ND 5.5) for
      particle-mediated epidermal delivery (PMED) of a nucleic acid vaccine against
      Hepatitis B virus (HBV). Healthy adults, previously immunized with licensed HBV
      vaccine, received a single boost vaccination of HBV nucleic acid vaccine
      administered by ND 5.5 or XR-1, the clinical research device used in previous
      clinical trials. Similar increases in anti-HBV surface antigen serum antibody
      titers and cell-mediated immune responses were produced by ND 5.5 and XR-1 when
      delivering comparable effective doses of the vaccine. The overall intensity of
      the immune response was lower in those subjects vaccinated with two, rather than
      4 administrations of vaccine delivered by ND 5.5. Skin reactions at sites of
      vaccine administration were equivalent with both devices. This is the first
      clinical demonstration of the safe and effective PMED of a nucleic acid vaccine
      with the ND 5.5 device.

PMID- 15985319
TI  - Attenuated immune response to tetanus toxoid in young healthy men protected
      against tetanus.
AB  - Tetanus booster is a routine procedure of tetanus prevention in populations with
      high risk of injury, independent of the levels of protection. But the immune
      response in already protected individuals is not well studied. We describe the
      kinetics of booster response in individuals by measuring tetanus antitoxin levels
      by indirect ELISA. A 6-month follow up was performed on 60 boosted individuals
      tested before, 1 week, 1, 2, 3 and 6 months after the booster. High initial
      protection (mean titer 1.08 IU/ml) and less than 3-fold increase after 1 month
      were observed. After 1 month of stable antitoxin levels, the levels slowly
      decreased and reached a mean titer of 1.78 IU/ml after 6 months. Individuals with
      initial levels <1 IU/ml had booster response after the first month twice as high
      compared to those with initial level >or=1 IU/ml. However, in both groups, the
      decline from 1 to 6 months was about 2-fold. Individuals already protected
      against tetanus exhibited an attenuated, short-lasting booster response to
      tetanus toxoid. This was more pronounced in individuals with pre-booster levels
      >or=1 IU/ml, who did not improve immune protection after the booster.

PMID- 15985320
TI  - Natural releases from contaminated groundwater, Example Reference Biosphere 2B.
AB  - Safety assessment is a tool which, by means of an iterative procedure, allows the
      evaluation of the performance of a disposal system and its potential impact on
      human health and the environment. Radionuclides from a deep geological disposal
      facility may not reach the surface environment until many tens of thousands of
      years after closure of the facility. The BIOMASS Programme on BIOsphere Modelling
      and ASSessment developed Examples of "Reference Biospheres" to illustrate the use
      of the methodology and to demonstrate how biosphere models can be developed and
      justified as being fit for purpose. The practical examples are also intended to
      be useful in their own right. The Example Reference Biosphere 2B presented here
      involves the consideration of alternative types of geosphere-biosphere interfaces
      and calculation of doses to members of hypothetical exposure groups arising from
      a wide range of exposure pathways within agricultural and semi-natural
      environments, but without allowing for evolution of the corresponding biosphere
      system. The example presented can be used as a generic analysis in some
      situations although it was developed around a relatively specific conceptual
      model. It should be a useful practical example, but the above numerical results
      are not intended to be understood as prescribed biosphere 'conversion factors'.

PMID- 15985321
TI  - Pathways to youth homelessness.
AB  - Research documents high levels of psychopathology among homeless youth. Most
      research, however, has not distinguished between disorders that are present prior
      to homelessness and those that develop following homelessness. Hence whether
      psychological disorders are the cause or consequence of homelessness has not been
      established. The aim of this study is to investigate causal pathways to
      homelessness amongst currently homeless youth in Australia. The study uses a
      quasi-qualitative methodology to generate hypotheses for larger-scale research.
      High rates of psychological disorders were confirmed in the sample 35 homeless
      youth aged 14-25. The rates of psychological disorders at the point of
      homelessness were greater than in normative samples, but the rates of clinical
      disorder increased further once homeless. Further in-depth analyses were
      conducted to identify the temporal sequence for each individual with a view to
      establishing a set of causal pathways to homelessness and trajectories following
      homelessness that characterised the people in the sample. Five pathways to
      homelessness and five trajectories following homelessness were identified that
      accounted for the entire sample. Each pathway constituted a series of
      interactions between different factors similar to that described by Craig and
      Hodson (1998. Psychological Medicine, 28, 1379-1388) as "complex subsidiary
      pathways". The major findings were that (1) trauma is a common experience amongst
      homeless youth prior to homelessness and figured in the causal pathways to
      homelessness for over half of the sample; (2) once homeless, for the majority of
      youth there is an increase in the number of psychological diagnoses including
      drug and alcohol diagnoses; and (3) crime did not precede homelessness for all
      but one youth; however, following homelessness, involvement in criminal activity
      was common and became a distinguishing factor amongst youth. The implications of
      these findings for future research and service development are discussed.

PMID- 15985322
TI  - Transverse retubularized ileal vaginoplasty: a new application of the Monti
      principle--preliminary report.
AB  - OBJECTIVE: The surgical management of the absence of the vagina is a complex
      problem and constitutes a significant technical challenge. Herein we present our
      successful experience with vaginal reconstruction by the use of a modified ileal
      segment according to the Monti principle. METHODS: Six patients aged from 23 to
      41 years (mean 33 years) were referred to our institution for vaginal stenosis.
      In our series, ileum has been used to create the neovagina: the isolated segment
      has been longitudinally detubularized and transversally retubularized in order to
      configure the roof of the neovagina. RESULTS: The mean operating time was 220
      min. No intra-operative complication occurred. The mean follow-up of this series
      was 16 months. At the latest follow-up, all patients had patent moist neovaginas,
      but excessive vaginal mucous was not a problem in any patient in our series.
      CONCLUSIONS: Neovaginal creation using isolated ileal segments according to the
      Monti channel principle provide excellent tissue for vaginal replacement,
      providing excellent patient satisfaction and relatively low morbidity. Cosmetic,
      functional and anatomical results were encouraging. In our opinion our technique
      may be indicated for all cases of vaginal absence: congenital abnormalities in
      the pediatric population, vaginal stenosis after treatment of pelvic tumors,
      severe vaginal scarring secondary to chronic inflammatory disease or in case of
      secondary correction after failure gender surgery.

PMID- 15985323
TI  - An age-structured model with delay mortality.
AB  - Many species experience aperiodic mortality. Yet, there is little or no
      understanding of how this event affects population dynamics. We have considered
      one of the most simple class of age-structured models, namely, the MacKendrick
      Von Foerster type equations with suitable modifications to suit the purpose of
      this study. The main result shows the effect of delay in the estimate of the
      population. If the delay parameter is taken as a period, then the model equations
      describe the dynamics of seasonal insects such as locusts whose large population
      decreases very fast.

PMID- 15985324
TI  - Sustainable systems as organisms?
AB  - Schrodinger [Schrodinger, E., 1944. What is Life? Cambridge University Press,
      Cambridge] marvelled at how the organism is able to use metabolic energy to
      maintain and even increase its organisation, which could not be understood in
      terms of classical statistical thermodynamics. Ho [Ho, M.W., 1993. The Rainbow
      and the Worm, The Physics of Organisms, World Scientific, Singapore; Ho, M.W.,
      1998a. The Rainbow and the Worm, The Physics of Organisms, 2nd (enlarged) ed.,
      reprinted 1999, 2001, 2003 (available online from ISIS website www.i-sis.org.uk)]
      outlined a novel "thermodynamics of organised complexity" based on a nested
      dynamical structure that enables the organism to maintain its organisation and
      simultaneously achieve non-equilibrium and equilibrium energy transfer at maximum
      efficiency. This thermodynamic model of the organism is reminiscent of the
      dynamical structure of steady state ecosystems identified by Ulanowicz
      [Ulanowicz, R.E., 1983. Identifying the structure of cycling in ecosystems. Math.
      Biosci. 65, 210-237; Ulanowicz, R.E., 2003. Some steps towards a central theory
      of ecosystem dynamics. Comput. Biol. Chem. 27, 523-530]. The healthy organism
      excels in maintaining its organisation and keeping away from thermodynamic
      equilibrium--death by another name--and in reproducing and providing for future
      generations. In those respects, it is the ideal sustainable system. We propose
      therefore to explore the common features between organisms and ecosystems, to see
      how far we can analyse sustainable systems in agriculture, ecology and economics
      as organisms, and to extract indicators of the system's health or sustainability.
      We find that looking at sustainable systems as organisms provides fresh insights
      on sustainability, and offers diagnostic criteria for sustainability that reflect
      the system's health. In the case of ecosystems, those diagnostic criteria of
      health translate into properties such as biodiversity and productivity, the
      richness of cycles, the efficiency of energy use and minimum dissipation. In the
      case of economic systems, they translate into space-time differentiation or
      organised heterogeneity, local autonomy and sufficiency at appropriate levels,
      reciprocity and equality of exchange, and most of all, balancing the exploitation
      of natural resources--real input into the system--against the ability of the
      ecosystem to regenerate itself.

PMID- 15985325
TI  - Complement-inhibiting effect of ovarian cancer antigen CA-125.
AB  - Malignant transformation of ovarian cells of surface epithelial origin is
      associated with expression of a membrane-spanning glycoprotein, cancer antigen
      (CA)-125. The bulk of the putative CA-125 molecule is comprised a very large,
      folded, multivalent, mucin-like exodomain. That the extracellular motif of CA-125
      exerts immunosuppressive effects which promote tumor progression has been
      suggested. We report that CA-125 attenuates complement lysis of antibody
      sensitized cells. The secreted form of CA-125 derived from culture medium of the
      human ovarian adenocarcinoma cell line OVCAR-3 caused a dose-response inhibition
      of sheep erythrocyte hemolysis. Moreover, OVCAR-3 cells became prone to
      complement attack (trypan blue uptake) mediated by a gonadotropin-releasing
      hormone receptor antibody when (membrane-bound) CA-125 was excised/removed by
      trypsin/washing; this effect was counteracted by replacement with (soluble) CA
      125. It is conceivable that CA-125 entraps/sheds effectors of the complement
      cascade.

PMID- 15985326
TI  - Assessment of microbial respiratory activity of a manufactured gas plant soil
      after remediation using sunflower oil.
AB  - Microbial activity of a manufactured gas plant (MGP) soil, as well as remaining
      oil degradability, before and after remediation using sunflower oil was assessed.
      A sandy soil contaminated with polycyclic aromatic hydrocarbons (PAHs) was
      collected from an MGP site in Berlin, Germany. Column solubilizations of PAHs
      from the field-moist soil and air-dried soil using sunflower oil as an extractant
      at an oil/soil ratio of 2:1 (v/m) were carried out to compare PAH removals from
      the soil under these two conditions. After column solubilizations, portions of
      untreated soil (UTS), solubilized field-moist soil (SFMS), and solubilized air
      dried soil (SADS) were amended with nutrients. Both nutrient amended and
      unamended soil samples were subjected to soil respiratory measurement. Soil
      respiration parameters, such as basal respiration rate, nutrient-induced
      respiration rate, lag time, exponential growth rate, respiratory activation
      quotient, peak maximum time, and cumulative CO2 evolution were calculated from
      the soil respiration curves. The parameters were compared using analysis of
      variance (ANOVA) and least-significance difference (LSD). Results showed that the
      impact of soil moisture on the PAH removals was quite significant, with the SADS
      showing higher PAH removals and the SFMS showing lower ones. There were
      significant differences between the respiration parameters with respect to the
      UTS, SFMS, and SADS. Basal respiration rate, nutrient-induced respiration rate,
      and exponential growth rate were lower for the SFMS and SADS relative to the UTS.
      Lag time and peak maximum time were higher for the SFMS and SADS relative to the
      UTS. Exponential growth rate was higher for the SFMS relative to the SADS. These
      parameters demonstrated that soil microbial activity was reduced at the onset of
      the test, because a lot of bioavailable materials for microbial growth were
      removed by sunflower oil. On the other hand, cumulative CO2 evolutions in the
      SFMS and SADS were higher than that in the UTS, indicating that soil respiration
      was activated after soil microorganisms got acclimatized to the remaining
      sunflower oil, and remaining sunflower oil was biodegradable.

PMID- 15985327
TI  - Potential application of coal-fuel oil ash for the manufacture of building
      materials.
AB  - In this paper coal-fuel oil ash has been characterized in terms of leaching
      behaviour and reactivity against lime and gypsum in hydratory systems for the
      manufacture of building materials. Its behaviour was also compared to that of
      coal ash. Metal release was measured in a dynamic leaching test with duration up
      to 16 days. The results have shown that coal-fuel oil ash behaves very similarly
      to coal ash. The reactivity of coal-fuel oil ash against lime and gypsum was
      measured in mixtures containing only lime and in mixtures containing both lime
      and gypsum. These systems were hydrated at 25 and 40 degrees C under 100% R.H.
      The results have shown that the main hydration products are the same as those
      that are usually formed in similar coal ash-based systems. That is, calcium
      silicate hydrate in coal-fuel oil ash/lime systems and calcium silicate hydrate
      plus calcium trisulphoaluminate hydrate in coal-fuel oil ash/lime/gypsum systems.
      From the quantitative point of view, hydration runs showed that the amounts of
      both chemically combined water and reacted lime measured in the case under
      investigation are very similar to those found in similar coal ash-based systems.
      Finally, the measurement of unconfined compressive strength proved that the
      systems have potentiality for the manufacture of pre-formed building blocks.

PMID- 15985328
TI  - The investigation of parameters affecting boron removal by electrocoagulation
      method.
AB  - Boron removal from wastewaters by electrocoagulation using aluminum electrode
      material was investigated in this paper. Several working parameters, such as pH,
      current density, boron concentration and type and concentration of supporting
      electrolyte were studied in an attempt to achieve a higher removal capacity. The
      experiments were carried out by keeping the pH of solution constant and optimum
      pH of solution was determined 8.0 for the aluminum electrode. Although energy
      consumption increased with decreasing boron concentration, which conductivity of
      these solutions were low, boron removal efficiency was higher at 100 mg/L than
      that of 1000 mg/L. Current density was an important parameter affecting removal
      efficiency. Boron removal efficiency and energy consumption increased with
      increasing current density from 1.2 to 6.0 mA/cm2. The types of different
      supporting electrolyte were experimented in order to investigate to this
      parameter effect on boron removal. The highest boron removal efficiency, 97%, was
      found by CaCl2. Added CaCl2 increased more the conductivity of solution according
      to other supporting electrolytes, but decreased energy consumption. The results
      showed to have a high effectiveness of the electrocoagulation method in removing
      boron from aqueous solutions.

PMID- 15985329
TI  - Characterization of a hazardous eyeliner (kohl) by confocal Raman microscopy.
AB  - A new method of analyzing kohl, a cosmetic eyeliner, using confocal Raman
      microscopy is reported. This technique offers an important alternative to
      conventional spectroscopic techniques that provide elemental/atomic composition.
      Raman spectra of three kohl samples have been measured between 150 and 3000 cm(
      1) at room temperature. The main component of two kohl samples was found to be
      lead(II) sulfide (PbS). Kohl is used as a traditional cosmetic and remedy in the
      Middle East, Far East, and Northern Africa. Since kohl products contain very high
      concentrations of lead, they constitute a risk for public health, particularly
      for children.

PMID- 15985330
TI  - Apamin produces selective improvements of learning in rats.
AB  - The effect of apamin on learning was examined using two behavioral tasks where
      the animals were subjected to two trials separated by a 24h interval. In the Y
      maze task, apamin administered before the acquisition session did not enhance
      performance on both the acquisition session and the restitution session. In the
      second behavioral task, animals were trained to press a lever to obtain a food
      pellet (fixed ratio 1). Then, to study the effect of apamin on extinction,
      animals were submitted to two sessions where a press on the lever was not
      reinforced. Apamin administered before the acquisition session reduced the number
      of lever presses during the first 3-min period of the restitution session. These
      results suggest that the blockade of SK channels could improve the acquisition
      but not when the task requires the processing of spatial information.

PMID- 15985331
TI  - Activation of NK1 receptor of trigeminal root ganglion via substance P paracrine
      mechanism contributes to the mechanical allodynia in the temporomandibular joint
      inflammation in rats.
AB  - The aim of this study was to investigate whether under in vivo conditions,
      temporomandibular joint (TMJ) inflammation alters the excitability of Abeta
      trigeminal root ganglion (TRG) neuronal activity innervating the facial skin by
      using extracellular electrophysiological recording with multibarrel-electrodes.
      Complete Freund's adjuvant (CFA) was injected into the rat TMJ. Threshold for
      escape from mechanical stimulation applied to the whisker pad area in inflamed
      rats (2 days) was significantly lower than that in control rats. A total of 36
      Abeta-TRG neurons responding to electrical stimulation of the whisker pad was
      recorded in pentobarbital-anesthetized rats. The number of Abeta-TRG neurons with
      spontaneous firings and their firing rate in TMJ inflamed rats were significantly
      larger than those in control rats. The firing rates of their spontaneous activity
      in the Abeta-TRG neurons were current-dependently decreased by local
      iontophoretic application of an NK1 receptor antagonist (L-703,606) in inflamed,
      but not non-inflamed rats. Their spontaneous activities were current-dependently
      increased by local iontophoretic application of substance P (SP) in control and
      inflamed rats. The mechanical response threshold of Abeta-TRG neurons in inflamed
      rats was significantly lower than that in control rats. The mechanical response
      threshold in inflamed rats after iontophoretic application of L-703,606 was not
      different from that in control rats. These results suggest that TMJ inflammation
      modulate the excitability of Abeta-TRG neurons innervating the facial skin via
      paracrine mechanism due to SP released from TRG neuronal cell body. Such a SP
      release may play an important role in determining the trigeminal inflammatory
      allodynia concerning the temporomandibular disorder.

PMID- 15985332
TI  - Identification of subgroups of persons with chronic pain based on profiles on the
      pain stages of change questionnaire.
AB  - This study sought to identify reliable subgroups of patients with chronic pain
      based on profiles of subscale scores on the Pain Stages of Change Questionnaire
      (PSOCQ), a reliable and valid measure of individuals' readiness to adopt a self
      management approach to chronic pain. The PSOCQ was administered to 633 people
      seeking treatment for chronic pain. Participants were predominantly White,
      averaged 48 years of age, about half were men, and about half reported back pain
      as the primary complaint. In a first study, cluster analysis was applied to 250
      respondents. Five clusters were identified and named Precontemplation (11.0% of
      the sample), Contemplation (18.0%), Noncontemplative Action (12.4%),
      Participation (25%), and Ambivalent (33.6%). Results of a discriminant function
      analysis (DFA) on this sample, using the solution from the cluster analysis
      yielded a total error rate of 0.036. In a second study, the results of the first
      DFA were applied to an independent sample of 383 respondents in order to cross
      validate the solution from the first study. Cluster assignment proportions were
      very similar to the first sample and the posterior probability error rate for the
      second DFA was 13%. As predicted, clusters did not differ on measures of pain,
      disability, or demographics. Moreover, clusters differed significantly in
      theoretically consistent directions by scores on the Survey of Pain Attitudes,
      thus demonstrating criterion related validity for the clusters. Future research
      should examine the utility of PSOCQ profiles, relative to individual PSOCQ scale
      scores alone, in predicting response to self-management treatment approaches.

PMID- 15985333
TI  - Testing of amplified fragment length polymorphism (AFLP) technique as a tool for
      molecular epidemiology of Trichinella nativa.
AB  - A total of nine Trichinella nativa isolates were compared by amplified fragment
      length polymorphism (AFLP). Four hundred nanograms of genomic DNA from a pool of
      10--20 larvae were digested using HindIII and MseI restriction endonucleases. Of
      the 16 primer combinations initially tested, Hind-C and Mse-C primers showed rich
      polymorphism with approximately 40--90 bands in the range of 30--270 bp. Genetic
      similarities were estimated visually. AFLP provided discriminatory banding
      patterns and may therefore be used as a method for detecting variation in T.
      nativa populations. However, the heterogeneous patterns obtained from pooled
      samples emphasize the need for further development of the sampling and numerical
      analysis of the patterns for epidemiological and taxonomical interpretation.

PMID- 15985334
TI  - Experimental studies in pigs on Trichinella detection in different diagnostic
      matrices.
AB  - A total of 72 specific pathogen-free (SPF) and Iberian pigs (three animals per
      group) were inoculated with 200, 1000 or 20,000 muscle larvae of T. spiralis, T.
      nativa, T. britovi and T. pseudospiralis. For each animal, the muscle larva
      burden was evaluated in nine muscle samples by digestion. The anti-Trichinella
      IgG kinetics in blood samples, taken twice prior and at days 5, 10, 15, 20, 25,
      30, 40, 50 and 60 post-inoculation, and in muscle juice, obtained at necropsy,
      was evaluated by an ELISA using an excretory/secretory antigen. The mean larval
      recovery rate in SPF/Iberian pigs corresponded with the level of inoculum dose,
      and tongue, diaphragm and masseter were identified as predilection muscles. In
      SPF and Iberian pigs receiving 20,000 larvae of T. spiralis, an earlier
      seroconversion was detected from day 25 post-inoculation. At a 10-fold dilution,
      the muscle juice showed a good test agreement with blood serum.

PMID- 15985335
TI  - Molecular cloning of a cDNA encoding a putative cuticle collagen of Trichinella
      spiralis.
AB  - A 5-day-old adult stage-specific cDNA fragment from Trichinella spiralis was
      identified by suppression subtractive hybridization and was used as a probe to
      screen the cDNA library. The cDNA sequence coding for a putative T. spiralis
      cuticle collagen was isolated. The cDNA encoded an open reading frame of 343
      amino acid residues with molecular weight of 35.1 k Da. The deduced protein
      contained an N-terminal signal peptide, a nematode cuticle collagen N-terminal
      domain and a collagen triple helix repeat domain. Searches in GenBank using
      BLASTP showed up to 47% identity to cuticle collagens from other nematodes.
      Southern blot analysis of genomic DNA indicated this gene was present as a single
      copy in T. spiralis genome.

PMID- 15985336
TI  - Basal cell carcinomas arising on a skin graft secondary to a thermal burn scar.

PMID- 15985337
TI  - A glove to sock dressing.

PMID- 15985338
TI  - Exfoliative dermatitis, fever and acute renal failure in a 60% burns patient.

PMID- 15985339
TI  - A randomised-controlled pilot study using nicotine patches with pregnant women.
AB  - Stopping smoking in pregnancy is a public health priority and a clinical
      imperative. However, many women who have not been able to 'quit' in early
      pregnancy find it very difficult to do so. This randomised-controlled pilot study
      examined feasibility issues in offering free nicotine patches with counselling to
      a group of 20 mid-trimester pregnant women at the Women's and Children's
      Hospital, Adelaide. A further 20 were offered counselling only. Smoking status at
      each visit was measured by self-report, carbon monoxide monitoring, and salivary
      cotinine. The most common pattern (eleven of the twenty women) was intermittent
      patch use. Only five women used patches continuously up to the 12 week maximum
      available. Three women in the patch group were abstinent at delivery compared
      with none in the control group. Notable features of the study were the low
      interest in participation and the high withdrawal rate. Nicotine patches may not
      be highly useful for pregnant women. Continuing tobacco control measures and
      customized support for women and their partners, often smokers, may prove more
      fruitful.

PMID- 15985340
TI  - Acidosis might make breast cancer cells more susceptible to metastasize by
      shifting CXCL12 monomer-dimer equilibrium to monomeric state.

PMID- 15985341
TI  - The future of 'pure' medical science: the need for a new specialist professional
      research system.
AB  - Over recent decades, medical research has become mostly an 'applied' science
      which implicitly aims at steady progress by an accumulation of small
      improvements, each increment having a high probability of validity. Applied
      medical science is, therefore, a social system of communications for generating
      pre-publication peer-reviewed knowledge that is ready for implementation.
      However, the need for predictability makes modern medical science risk-averse and
      this is leading to a decline in major therapeutic breakthroughs where new
      treatments for new diseases are required. There is need for the evolution of a
      specialized professional research system of pure medial science, whose role would
      be to generate and critically evaluate radically novel and potentially important
      theories, techniques, therapies and technologies. Pure science ideas typically
      have a lower probability of being valid, but the possibility of much greater
      benefit if they turn out to be true. The domination of medical research by
      applied criteria means that even good ideas from pure medical science are
      typically ignored or summarily rejected as being too speculative. Of course,
      radical and potentially important ideas may currently be published, but at
      present there is no formal mechanism by which pure science publications may be
      received, critiqued, evaluated and extended to become suitable for 'application'.
      Pure medical science needs to evolve to constitute a typical specialized
      scientific system of formal communications among a professional community. The
      members of this putative profession would interact via close research groupings,
      journals, meetings, electronic and web communications--like any other science.
      Pure medical science units might arise as elite grouping linked to existing world
      class applied medical research institutions. However, the pure medical science
      system would have its own separate aims, procedures for scientific evaluation,
      institutional organization, funding and support arrangements; and a separate
      higher-professional career path with distinctive selection criteria. For
      instance, future leaders of pure medical science institutions would need to be
      selected on the basis of their specialized cognitive aptitudes and their record
      of having generated science-transforming ideas, as well as their research
      management skills. Pure medical science would work most effectively and
      efficiently if practiced in many independent and competing institutions in
      several different countries. The main 'market' for pure medical science would be
      the applied medical scientists, who need radical strategies to solve problems
      which are not yielding to established methods. The stimulus to create such elite
      pure medical science institutions might come from the leadership of academic
      'entrepreneurs' (for instance, imaginative patrons in the major funding
      foundations), or be triggered by a widespread public recognition of the probable
      exhaustion of existing applied medical science approaches to solving major
      therapeutic challenges.

PMID- 15985342
TI  - Genetic and antigenic characterization of the surface lipoprotein P48 of
      Mycoplasma bovis.
AB  - The presence of a membrane lipoprotein homologous to the P48 of Mycoplasma
      agalactiae was investigated in different Mycoplasma bovis isolates selected by
      geographical locations and biological properties. Its potential as a diagnostic
      tool was also discussed. The presence of a specific signal observed in all M.
      bovis field isolates probed with a rabbit antiserum raised against the M.
      agalactiae recombinant P48 demonstrated that this protein is structurally and
      antigenically conserved within the M. bovis cluster. No signal was detected when
      testing six different mycoplasma species found in cattle. The p48 gene was
      identified by PCR approach and partially sequenced. Full length gene sequence was
      obtained by direct bacterial chromosome sequencing. Five UGAs were selectively
      mutated into UGG and the full length mutated gene, lacking the signal peptide,
      was cloned and expressed in Escherichia coli. The purified recombinant antigen (r
      P48) was evaluated as a potential marker of infection using a panel of 86 well
      characterized sera from experimentally and naturally infected cattle. Specific
      IgM antibodies were detected within 6-9 days after experimental infection
      followed by an IgG response lasting from the third/fourth week after contact.
      Although antibody titers were well below those observed in sheep or goats
      infected with M. agalactiae, results suggest that M. bovis r-P48 can be used as a
      specific marker of infection.

PMID- 15985344
TI  - Histological and ultrastructural analysis of cryopreserved sheep preantral
      follicles.
AB  - The aim of this study was to verify the histological and ultrastructural
      characteristics of sheep preantral follicles after exposure of ovarian tissue to
      cryopreservation in glycerol (GLY), ethylene glycol (EG), propanediol (PROH) or
      dimethyl sulfoxide (DMSO) in order to determine the optimum method to store sheep
      ovarian tissue for later experimental or clinical use. Each ovarian pair from
      five mixed-breed ewes was divided into 17 fragments. One (control) fragment was
      immediately fixed for routine histological and ultrastructural studies and the
      remaining (test) fragments were randomly distributed in cryotubes, equilibrated
      at 20 degrees C/20 min in 1.8 mL of minimal essential medium (MEM) containing 1.5
      or 3 M GLY, EG, PROH or DMSO and then either fixed for morphological studies to
      determine their possible toxic effect or frozen/thawed and then fixed to test the
      effect of cryopreservation on preantral follicles. Histological analysis showed
      that, compared to control fragments, all cryoprotectants at both concentrations
      significantly reduced the percentage of normal preantral follicles in ovarian
      fragments prior to or after cryopreservation. PROH 3.0 M appeared to exert a more
      toxic effect (P<0.05) than the other cryoprotectants in noncryopreserved tissues.
      After freezing/thawing, the highest (P<0.05) percentages of lightmicroscopical
      normal preantral follicles were observed in ovarian fragments cryopreserved in EG
      (1.5 and 3 M) or DMSO (1.5 M). However, transmission electronic microscopical
      (TEM) examination showed that only the DMSO-cryopreserved preantral follicles had
      normal ultrastructure. The data suggest that sheep preantral follicles should be
      cryopreserved with 1.5 M DMSO for later clinical or experimental application.

PMID- 15985345
TI  - Lactation weight loss influences subsequent reproductive performance of sows.
AB  - In order to examine the effect of different lactation weight losses of sows of
      different parity on subsequent reproductive performance, the present trial was
      performed in German (n = 4) and Slowakian (n = 11) indoor pig breeding units (n =
      1677 sows evaluated). Weaning-to-service-intervals, farrowing rates and total
      born litter sizes in sows with different lactation weight losses were compared.
      Sows were categorized according to lactation weight losses of <5%, 5-10%, 11-15%,
      16-20%, >20%. Lactation weight losses exerted a quadratic effect (P < 0.01) on
      weaning-to-service-intervals. When analyzed across parity categories, with parity
      category included as a fixed effect, the weaning-to-service-intervals appeared to
      be minimized at lactation weight losses of <5%. Weaning-to-service-intervals
      increased (P < 0.05) when lactation weight losses increased above 5% for parity 1
      sows, but not until lactation weight losses exceeded 10% for animals of parity 2
      and more. There was a parity effect observed at lactation weight losses of <10%,
      P < 0.05, but the difference was not significant any more at lactation weight
      losses of >10%. Lactation weight losses >10% had a negative (P < 0.05) effect on
      subsequent farrowing rates to first service. The difference was higher (P < 0.01)
      in sows with lactation weight losses >20%. Lactation weight losses exerted a
      negative (P < 0.001) effect on total-born litter sizes in parity 1 versus parity
      >5 and parity 1 versus parity 2-5 sows at lactation weight losses of >10%.
      CONCLUSION: As weight loss of sows during lactation increases subsequent
      reproduction performance decreases.

PMID- 15985346
TI  - Response of goat sperm to hypoosmotic steps modelled probit analysis.
AB  - Hypoosmotic swelling test (HOS) has been proposed by many authors to evaluate the
      functional integrity of the sperm membrane. Our approach in this experiment has
      consisted in exposing spermatozoa to a wide range of osmotic pressures then
      evaluating the reacted sperm cells by flow cytometry and finally modelling the
      sperm cell responses. Semen samples were diluted in skim milk or NPPC (native
      phosphocaseinate) extenders, and stored at 4 degrees C for 3 days. At D0 and D3
      aliquots from each ejaculate (n=12) were submitted to seven hypoosmotic solutions
      varying from 230 to 10mOsm/kg. Sperm samples were analyzed using flow cytometry
      to determine two populations of spermatozoa identified by propidium iodide (PI):
      PI+ (including PI, red fluorescence) and PI- (excluding PI, no fluorescence).
      Spermatozoa PI+ were considered as spermatozoa with membrane damages. PI+
      exhibited a high variation from 230 to 10mOsm/kg which was considered as a dose
      response curve. Data were modelled using Mixed procedure and probit analysis to a
      sigmoid curve. Each model curve characterized the profile of response of the
      variable PI+ to the range of osmotic pressure from 230 to 10mOsm/kg. The
      estimated parameters modelling the sigmoid curves are discussed in order to
      evaluate the effect of extender (skim milk versus NPPC) and duration of
      preservation (D0 versus D3). Such modelling could help to differentiate storage
      method ejaculates within males or between male, contributing therefore to improve
      semen technology.

PMID- 15985347
TI  - PIXI bone density screening for osteoporosis in postmenopausal women.
AB  - OBJECTIVES: The aim of this study was to evaluate a pragmatic screening programme
      for osteoporosis based on the identification of known risk factors. A secondary
      aim was to assess the validity of peripheral instantaneous X-ray imager (PIXI)
      scanning against dual energy X-ray absorptiometry (DEXA) in women identified as
      having osteopenia. METHODS: A cross-sectional two stage screening programme. The
      study was carried out in 14 practices in Surrey. Women aged 60-80 years of age
      were screened with a questionnaire. Those identified with one or more risk
      factors were offered a PIXI scan of the ankle in their own surgery. Those with an
      intermediate score on PIXI scan were offered a DEXA scan of hip, spine and
      forearm. RESULTS: Four thousand six hundred and forty-six women completed
      questionnaires, 2688 had a PIXI scan and 553 were found to be at high risk of
      osteoporosis. Multivariate analysis identified the three most important risk
      factors associated with increased risk of osteoporotic fracture as age, a
      previous fracture and the presence of a stooped posture. Hormone replacement
      therapy (HRT) was shown to be protective. Twenty three percent of women with an
      intermediate score on PIXI scan were found to have osteoporosis on DEXA scan of
      hip and spine. CONCLUSIONS: PIXI scanning proved acceptable, practicable but only
      had moderate comparability with DEXA. The findings suggest that patients over the
      age of 60 years with a history of a fracture or evidence of spinal collapse are
      likely to have osteoporosis and should be offered screening. HRT past the
      menopause would seem to confer benefit and the recent reduction in its use may
      lead to increasing numbers of women suffering osteoporotic fractures.

PMID- 15985348
TI  - The relative flow of the walls of phospholipid tether bilayers.
AB  - Lipid nanotubes or "tethers" can be formed from liposomes or niosomes, pulled
      from the parent vesicles by micromanipulation. The tethers are cylindrical
      multibilayer tubes. Here, we describe the movement of these multilamellar walls,
      initiated by creating a surface tension gradient along the tether. The movement
      of lipid can give rise to a visible moving boundary. In the case of bilayer
      membranes, a tangential gradient in surface tension produces membrane bulk flow
      toward regions of higher surface tension. The flow of the bilayers comprising the
      tether nanotubes seems to be restricted to the inner bilayers, creating a
      velocity gradient in the bilayers. In this study, we discuss the implementation
      of tension-driven flows as a transport method in a tether-vesicle network.
      Interactions between fluid within the tether channels and the lipid layers are
      important, leading to anomalies in the transport of fluids and particles compared
      to bulk systems.

PMID- 15985350
TI  - Detection of galangin-induced cytoplasmic membrane damage in Staphylococcus
      aureus by measuring potassium loss.
AB  - Galangin is one of the active antimicrobial principles of propolis or 'bee glue'
      and Helichrysum aureonitens, a perennial herb used by South African indigenes to
      treat infection. The effect of this compound and antibacterial agents with known
      mechanisms of action upon the cytoplasmic membrane integrity of Staphylococcus
      aureus was investigated by comparing potassium loss profiles from bacterial cell
      suspensions. Using an agar dilution assay, the minimum inhibitory concentrations
      (MICs) of the flavonol galangin, the bacteriostatic antibiotic novobiocin and the
      bactericidal antibiotic penicillin G against Staphylococcus aureus NCTC 6571 were
      determined as being 50 microg/mL, 62.5 ng/mL and 31.3 ng/mL, respectively. When
      5x10(7)cfu/mL Staphylococcus aureus were suspended in 'potassium-free' media
      containing 50 microg/mL galangin, a 60-fold decrease in viability was observed
      after 12 h. Populations of 1x10(9) cfu/mL Staphylococcus aureus incubated for 12
      h in 50 microg/mL galangin lost 21% more potassium than untreated control
      populations. Novobiocin had no effect on potassium loss, but populations
      incubated in 31.3 ng/mL penicillin G exhibited a 6% increase in potassium loss.
      This data clearly demonstrates that galangin causes a significant increase in
      potassium loss from Staphylococcus aureus cells, which may be attributed to
      either direct damage to the cytoplasmic membrane or indirect damage effected
      through autolysis/weakening of the cell wall and consequent osmotic lysis.

PMID- 15985351
TI  - Gastroprotective effect of the Mapuche crude drug Araucaria araucana resin and
      its main constituents.
AB  - The resin from the tree Araucaria araucana (Araucariaceae) has been used since
      pre-columbian times by the Mapuche amerindians to treat ulcers. The
      gastroprotective effect of the resin was assessed in the ethanol-HCl-induced
      gastric ulcer in mice showing a dose-dependent gastroprotective activity at 100,
      200 and 300 mg/kg per os. The main three diterpene constituents of the resin,
      namely imbricatolic acid, 15-hydroxyimbricatolal and 15-acetoxyimbricatolic acid
      were isolated and evaluated for gastroprotective effect at doses of 50, 100 and
      200 mg/kg. A dose-related gastroprotective effect with highly significant
      activity (P<0.01) was observed at doses up to 200 mg/kg. At 100 mg/kg, the
      highest gastroprotective activity was provided by 15-hydroxyimbricatolal and 15
      acetoxyimbricatolic acid, all of them being as active as the reference drug
      lansoprazole at 20 mg/kg. The cytotoxicity of the main diterpenes as well as
      lansoprazole was studied towards human lung fibroblasts (MRC-5) and determined by
      the MTT reduction assay. A concentration-dependent cell viability inhibition was
      found with IC50 values ranging from 125 up to 290 microM. Our results support the
      traditional use of the Araucaria araucana resin by the Mapuche culture.

PMID- 15985352
TI  - Short tandem repeat (STR) genotyping of keratinised hair. Part 1. Review of
      current status and knowledge gaps.
AB  - We present a review of the literature on procedures for obtaining short tandem
      repeat (STR) genotypes from keratinised hair, being either hair shaft or telogen
      phase (naturally shed) hairs without associated scalp, follicle or sheath cells.
      Both the hair shaft and the telogen hair club have been subjected to the DNA
      degrading keratinisation process and are more likely to be found at a crime scene
      than anagen (plucked) or catagen phase hairs. We discuss human hair structure,
      the human hair growth cycle, the keratinisation process and their implications
      for DNA extraction procedures, PCR amplification strategies and the
      interpretation of STR genotypes. Knowledge gaps and areas requiring research are
      identified and are the subject of a second article in this series.

PMID- 15985353
TI  - Muscle mass loss in Rhesus monkeys: age of onset.
AB  - Sarcopenia, the decline in skeletal muscle mass and function with age,
      contributes to increased frailty and decreased functional performance in the
      aging human population. The negative health consequences of muscle mass loss
      emphasize the need for development of a nonhuman primate model for the prevention
      or attenuation of sarcopenia. The age of onset for muscle mass loss in Rhesus
      macaques was determined using three datasets; (i) dual-energy X-ray
      absorptiometry (DXA) data from a cross-sectional study of 90 adult Rhesus
      monkeys; (ii) lean tissue mass and estimated skeletal muscle mass (ESM) from 727
      DXA scans taken in 38 monkeys in a long-term, longitudinal aging study; and,
      (iii) quadriceps weights taken at necropsy from 13 male and 28 female Rhesus
      monkeys. These data indicate that both male and female Rhesus monkeys develop
      sarcopenia with age. The onset of sarcopenia is 14.1 +/- 2.8 years in females and
      15.8 +/- 2.5 years in males. Muscle loss reaches 20% in males by 23.2 years of
      age and in females by 24.5 years of age. Furthermore, our data indicate
      percentage declines in ESM similar to those seen in humans with advancing age.
      These data support the suitability of the Rhesus monkey as a primate sarcopenia
      model.

PMID- 15985354
TI  - Determination of aminoheterocycle and azabicycle in gliclazide bulk by capillary
      zone electrophoresis with amperometric detection.
AB  - A simple, reliable and reproducible method, based on capillary zone
      electrophoresis with amperometric detection (CZE-AD), was developed for
      simultaneous determination of 3-amino-3-azabicyclo[3,3,0]octane
      (aminoheterocycle) and 3-azabicyclo[3,3,0]octane (azabicycle) in gliclazide bulk
      drug. The optimal conditions of CZE-AD were 50 mM borate solution (pH 9.0) as
      running buffer, 14 kV as separation voltage and 0.95 V (versus SCE) as detection
      potential. Under the selected optimum conditions, the two analytes could be
      perfectly separated within 9 min. The linearity range of aminoheterocycle was
      from 1.0 x 10(-6) to 1.0 x 10(-3) M and that of azabicycle was from 2.0 x 10(-6)
      to 1.0 x 10(-3) M. Their detection limits were 5.0 x 10(-7) and 1.0 x 10(-6) M,
      respectively, (S/N=3). This proposed method demonstrated long-term stability and
      reproducibility with relative standard deviations of less than 2% for both
      migration time and peak current. It has been successively used for the
      determination of these two analytes in gliclazide bulk drug, and the assay
      results were satisfactory.

PMID- 15985355
TI  - The inclusion complexes of hesperetin and its 7-rhamnoglucoside with (2
      hydroxypropyl)-beta-cyclodextrin.
AB  - The effect of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) on the solubility
      properties and spectroscopic features of hesperetin and its 7-rhamnoglucoside,
      hesperidin, was qualitatively and quantitatively investigated in water, by means
      of UV-vis absorption and fluorescence spectroscopy. The stoichiometric ratios and
      stability constants describing the extent of formation of the complexes have been
      determined by phase-solubility measurements; in both cases type-A(L) diagrams
      have been obtained (soluble 1:1 complexes). The higher degree of interaction
      showed by hesperetin may be attributed to the higher hydrophobicity and smaller
      size of the aglycone molecule, which therefore exhibits a greater affinity for
      the CyD and fits better into the cavity. The effect of molecular encapsulation on
      the two flavanones antioxidant activity was afterwards evaluated by means of
      different biological assays, concerned to the different mechanisms of in vivo
      action. The protection efficacy was in all cases higher for the complexed drugs,
      with respect to the free ones; these results are of great interest for their
      potential usefulness in pharmaceutics.

PMID- 15985356
TI  - Development and validation of a radioreceptor assay for the determination of
      morphine and its active metabolites in serum.
AB  - This article describes the development and validation of a radioreceptor assay
      for the determination of morphine and morphine-6-beta-glucuronide (M6G) in serum.
      The assay is based on competitive inhibition of the mu-opioid-selective
      radiolabeled ligand [3H]-DAMGO by opioid ligands (e.g. M6G) for binding to the
      striatal opioid receptor. The assay has been validated according to the
      Washington Conference Report on Analytical Method Validation. The radioreceptor
      assay can be performed in serum without prior pre-treatment of the sample. Direct
      addition of the sample results in no significant loss in maximal binding sites,
      and therefore, no loss in sensitivity. The assay proves to be selective for a
      multitude of opioid agonists and antagonists (e.g. morphine IC50 = 4.1 nM and M6G
      IC50 = 12.8 nM). Moreover, morphine-3-glucuronide (M3G) displays a low affinity
      (IC50 = 1100 nM) for the mu-opioid receptor and according to the literature
      demonstrates no analgesic activity. This makes discrimination, in relation to the
      analgesic effect, of the two metabolites of morphine possible. The assay is fast
      (assay time <4h, analysis 5 min/sample), easy and the sensitivity (limit of
      detection (LOD) = 1.6 nM M6G-equivalents) is such that very potent agonists, like
      morphine and M6G, can be measured at the desired serum levels. The assay is
      accurate (<18%), but precision is limited if measured over several days (>35%).
      The assay is most accurate and precise if measured over a range from 3.5 to 40 nM
      M6G-equivalents. Based on the limited inter-assay precision, we propose to use
      this receptor assay mainly as a screening tool for neonates treated with
      morphine.

PMID- 15985357
TI  - Study of the interaction between fluoroquinolones and bovine serum albumin.
AB  - The mechanism of interaction between norfloxacin (NRF) and ciprofloxacin (CPF)
      with bovine serum albumin has been investigated using circular dichroism,
      fluorescence and absorption spectroscopy. The quenching mechanism of fluorescence
      of bovine serum albumin by fluoroquinolones was discussed. The binding sites
      number n and apparent binding constant K were measured by fluorescence quenching
      method. The thermodynamic parameters obtained from data at different temperatures
      were calculated. The distance r between donor (bovine serum albumin) and acceptor
      (fluoroquinolones) was obtained according to Forster theory of non-radiation
      energy transfer. The effect of common ions on binding constant was also
      investigated. The results of synchronous fluorescence spectra, UV-vis absorption
      spectra and circular dichroism of BSA in presence of fluoroquinolones show that
      the conformation of bovine serum albumin changed.

PMID- 15985358
TI  - Plant food allergens--structural and functional aspects of allergenicity.
AB  - The three dominating plant food allergen groups belong to the prolamin and cupin
      superfamilies and to the family 10 of pathogenesis-related proteins. The prolamin
      superfamily comprises allergenic 2S albumins, nonspecific lipid transfer proteins
      and cereal alpha-amylase/trypsin inhibitors. These allergens have related
      structures and are stable to thermal processing and proteolysis. The cupin
      superfamily comprises the allergenic 7S and 11S globulin storage proteins from
      peanuts, soybean and tree nuts which are heat stable and can form immunogenicity
      enhancing aggregates. The Bet v 1 family of allergens includes tree pollinosis
      associated food allergens with low stability which induce the symptoms of the
      oral allergy syndrome.

PMID- 15985359
TI  - Proceedings from the 5th International Conference on Farm Animal Endocrinology
      (Part 2). July 4-6, 2004, Budapest, Hungary.

PMID- 15985360
TI  - Cloning, expression and purification of feline proinsulin.
AB  - Feline proinsulin was cloned and expressed using a bacterial expression system.
      It was then purified from inclusion bodies using size exclusion chromatography
      and further processed including reduction of the protein. Following refolding,
      proinsulin was purified by reversed-phase high-performance liquid chromatography
      (RP-HPLC). RP-HPLC and mass spectrometric analysis indicated that the proinsulin
      contained the correct disulfide bridging pattern. This proinsulin can be used for
      therapeutic and diagnostic purposes.

PMID- 15985361
TI  - Roles of protein kinase C in regulation of P2X7 receptor-mediated calcium
      signalling of cultured type-2 astrocyte cell line, RBA-2.
AB  - The role of protein kinase C (PKC) on regulation of P2X(7) receptor-mediated
      Ca(2+) signalling was examined on RBA-2 astrocytes. Activation of PKC decreased
      the receptor-mediated Ca(2+) signalling and the decrease was restored by PKC
      inhibitors. Down regulation of PKC also caused a decrease in the Ca(2+)
      signalling. Thus PKC might play a dual role on the P2X(7) receptor signalling.
      Successive stimulation of the P2X(7) receptor induced a gradual decline of Ca(2+)
      signalling but PKC inhibitors failed to restore the decline. Nevertheless, PMA
      stimulated translocation of PKC-alpha, -betaI, -betaII, and -gamma, but only anti
      PKC-gamma co-immunoprecipitated the receptors. To examine the role of PKC-gamma,
      Ca(2+) signalling was measured by Ca(2+) imaging. Our results revealed that the
      agonist-stimulated Ca(2+) signalling were reduced in the cells that the
      transfection of either P2X(7) receptor or PKC-gamma morpholino antisense oligo
      was identified. Thus, we concluded that PKC-gamma interacted with P2X(7) receptor
      complex and positively regulated the receptor-mediated Ca(2+) signalling.

PMID- 15985362
TI  - Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive
      persons with schizotypal personality disorder.
AB  - INTRODUCTION: Schizotypal personality disorder (SPD) shares with schizophrenia
      many biological features, yet little is known about the clinical characteristics
      of persons diagnosed with this disorder. This report describes the clinical,
      cognitive and socio-occupational characteristics of a community sample of
      subjects diagnosed with SPD. METHOD: Sixty-four male and 40 female neuroleptic
      naive DSM-IV SPD subjects and 59 male and 51 female comparison subjects were
      recruited from the community for a total sample of 214 subjects. Demographic and
      cognitive differences between groups and, within the SPD group, the effect of
      gender on clinical features, such as the SPD criteria, SAPS, SANS, Schizotypal
      Personality Questionnaire, and co-morbidity, were examined using ANOVA and Chi
      square distributions. RESULTS: SPD subjects, in contrast to comparison subjects,
      had significantly lower socio-economic status, poorer social relationships and
      skills, and lower vocabulary scores. Furthermore, SPD subjects demonstrated more
      impairment on Vocabulary scores than on Block Design, as measured by the WAIS-R,
      a pattern not seen in comparison subjects. In the SPD cohort, positive symptoms
      predominated and nearly half were co-morbid for major depression. With respect to
      gender, male SPD subjects, compared with female SPD subjects, evinced
      significantly more negative symptoms, fewer friends, had more odd speech, and
      were more likely to also suffer from paranoid and narcissistic personality
      disorders. In contrast to male SPD subjects, female SPD subjects perceived
      themselves to be more disorganized. CONCLUSIONS: SPD subjects, similar to
      schizophrenics, are impaired socially, occupationally, and cognitively,
      particularly in the area of verbal measures. Moreover, male SPD subjects may be
      more severely affected than female SPD subjects across multiple domains of
      functioning.

PMID- 15985364
TI  - Second-generation beta-oxidation resistant 3-oxa-lipoxin A4 analogs.
AB  - Lipoxin A4 (LXA4) and aspirin-triggered 15-epi-LXA4 are structurally and
      functionally distinct eicosanoids, with potent anti-inflammatory and
      immunomodulatory actions. Therapeutic use of LXA4 is greatly limited by its rapid
      metabolism in vivo and chemical instability. First-generation synthetic LXA4
      analogs such as methyl (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15
      trihydroxy-7,9,11,13-hexadecatetraenoate (2, ATLa), were designed to minimize
      metabolism from the omega-end of the molecule. Pharmacokinetic analysis of ATLa
      revealed beta-oxidation as a novel route for LXA4 metabolism, prompting the
      development of second-generation 3-oxa-LXA4 analogs with improved pharmacokinetic
      disposition. Second-generation 3-oxa-LXA4 analogs such as
      (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-3-oxa-5,6,15-trihydroxy-7,9,11,13
      hexadecatetraenoic acid (3), have shown potency and efficacy comparable to ATLa
      in diverse animal models after topical, intravenous or oral delivery. These
      include several acute (2-24 h) inflammatory reactions: calcium ionophore-induced
      skin edema and inflammation (topical), LTB4/PGE2-induced skin inflammation and
      vascular leak (topical), zymosan A-induced peritonitis (i.v. and oral) and
      ischemia-reperfusion-induced secondary organ injury (i.v.). Remarkably, 3-oxa
      LXA4 analogs have potent once daily oral efficacy in preventing and promoting the
      resolution of established colitis induced by the hapten trinitrobenzene sulphonic
      acid (TNBS), an acute/chronic 7-14-day model of Crohn's disease. The second
      generation 3-oxa-LXA4 analogs thus provide new stable pharmacophores with which
      to explore the emerging role of lipoxins as a new therapeutic principle for
      regulating inflammation, allergy and immune dysfunction in preclinical and
      clinical research.

PMID- 15985363
TI  - Pharmacokinetics of theophylline in diabetes mellitus rats: induction of CYP1A2
      and CYP2E1 on 1,3-dimethyluric acid formation.
AB  - Pharmacokinetic parameters of theophylline and one of its metabolites, 1,3
      dimethyluric acid (1,3-DMU), were compared after intravenous and oral
      administration of aminophylline, 5mg/kg as theophylline, to diabetes mellitus
      rats induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective
      control rats. In DMIA and DMIS rats, expression of CYP1A2 and 2E1 increased
      approximately three times. Theophylline was metabolized to 1,3-DMU by CYP1A2 and
      2E1 in rats. Hence, it was expected that formation of 1,3-DMU increased in DMIA
      or DMIS rats. This was proven by the following results. First, after intravenous
      administration of theophylline, the AUC of 1,3-DMU was significantly greater in
      DMIA (110% increase) or DMIS (47.4% increase) rats. Second, the AUC of
      theophylline was significantly smaller in DMIA (26.1% decrease) or DMIS (30.1%
      decrease) rats because of significantly faster time-averaged total body clearance
      in DMIA (34.8% increase) or DMIS (42.7% increase) rats. Third, based on in vitro
      hepatic microsomal studies, intrinsic 1,3-DMU formation clearances were
      significantly faster in DMIA (20.4% increase) or DMIS (30.7% increase) rats than
      respective control rats. Similar results (AUC values of theophylline and 1,3-DMU)
      were also obtained after oral administration.

PMID- 15985365
TI  - The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for
      the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11beta
      hydroxylase) inhibitors.
AB  - Aldosterone plays a key role in salt and water homeostasis but is also involved
      in the development and progression of congestive heart failure and myocardial
      fibrosis. As a new pharmacological strategy for the treatment of these diseases,
      we propose the inhibition of the key enzyme of mineralcorticoid formation,
      CYP11B2 (aldosterone synthase). For studies of the effects of CYP11B2 inhibitors
      on the adrenal cortex, we selected the NCI-H295R cell line which expresses most
      of the key enzymes necessary for steroidogenesis. To evaluate this cell line as a
      test system for effects and side effects of CYP inhibitors, we established assays
      using radiolabeled substrates of CYP11B2 and CYP11B1 and subsequently tested a
      series of CYP11B2 inhibitors including the CYP19 inhibitor fadrozole. Fadrozole
      and compounds 6, 9 and 10 were more potent towards CYP11B2 compared to CYP11B1
      with IC(50) values in the nanomolar range. To analyze their overall effect, the
      formation of steroids in the cell culture supernatant was monitored. All
      compounds led to a concentration-dependent reduction of the aldosterone secretion
      but also reduced the formation of cortisol and androgens. In conclusion, the
      H295R cell line is a suitable tool for the prediction of overall side effects of
      CYP11B2 inhibitors on steroidogenesis.

PMID- 15985366
TI  - GAAAATATGATA-like elements in androgen-associated regulation of the prostatic
      acid phosphatase gene.
AB  - Purpose of the study was to clarify molecular mechanisms behind tissue-specific
      and hormone-dependent gene expression using human prostatic acid phosphatase
      (hPAP) gene as a model. Regulatory region -734/+467 of hPAP gene induces
      transcription of a reporter gene in the prostate of transgenic mice. It contains
      five elements, A-E, homologous to GAAAATATGATA sequence, which is connected to
      prostate-specific and androgen-dependent gene expression. The significance of the
      C, D and E elements in the transcriptional regulation of hPAP gene was evaluated
      using reporter gene assays. The deletion of element C from the hPAP promoter
      constructs mainly decreased their transcriptional activity in the presence of
      androgen, while increased activity particularly in the absence of androgens was
      detected after removal of elements D and E. These events took place in
      transiently transfected prostatic LNCaP cells, but not in non-prostatic COS-1
      cells. As a conclusion, the GAAAATATGATA-like elements are involved in the
      transcriptional regulation of hPAP promoter constructs in prostatic cells. These
      elements mediate both transcriptional activation and repression depending on the
      hormonal status of the cells and location of the element in the construct.

PMID- 15985367
TI  - Novel biosensors for the detection of estrogen receptor ligands.
AB  - There exists a significant need for the detection of novel estrogen receptor (ER)
      ligands for pharmaceutical uses, especially for treating complications associated
      with menopause. We have developed fluorescence resonance energy transfer (FRET)
      based biosensors that permit the direct in vitro detection of ER ligands. These
      biosensors contain an ER ligand-binding domain (LBD) flanked by the FRET donor
      fluorophore, cyan fluorescent protein (CFP), and the acceptor fluorophore, yellow
      fluorescent protein (YFP). The ER-LBD has been modified so that Ala 430 has been
      changed to Asp, which increases the magnitude of the FRET signal in response to
      ligand-binding by more than four-fold compared to the wild-type LBD. The binding
      of agonists can be distinguished from that of antagonists on the basis of the
      distinct ligand-induced conformations in the ER-LBD. The approach to binding
      equilibrium occurs within 30min, and the FRET signal is stable over 24h. The
      biosensor demonstrates a high signal-to-noise, with a Z' value (a statistical
      determinant of assay quality) of 0.72. The affinity of the ER for different
      ligands can be determined using a modified version of the biosensor in which a
      truncated YFP and an enhanced CFP are used. Thus, we have developed platforms for
      high-throughput screens for the identification of novel estrogen receptor
      ligands. Moreover, we have demonstrated that this FRET technology can be applied
      to other nuclear receptors, such as the androgen receptor.

PMID- 15985368
TI  - Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia-
      case report and literature review.
AB  - Male breast cancer is a rare disease. Atypical ductal hyperplasia (ADH) in men is
      much rarer, and bilateral involvement is exceptional. A 20-year-old male
      presented with bilateral gynaecomastia who underwent subcutaneous mastectomies
      and histopathology revealed bilateral ADH. At 24 months, completion mastectomies
      were performed on both sides. The residual breast tissue revealed ADH similar to
      the initial specimen. ADH in women increases the risk of breast cancer by four to
      five times. To our knowledge, this is the first case report of bilateral ADH in a
      gynaecomastia specimen.

PMID- 15985369
TI  - Relationship between prognostic factors of breast cancer and 99mTc-sestamibi
      uptake in patients who underwent scintimammography: Multivariate analysis of
      causes of false-negative results.
AB  - The complementary role of sestamibi scintimammography (SSM) in patients with
      breast cancer (BC) is well established. The aim of this study was to establish
      whether a relationship exists between sestamibi uptake, evaluated as a tumour-to
      background ratio (TBR), and the main prognostic factors of BC. SSM with the
      measurement of TBR was performed preoperatively in 102 women (median age 57
      years, range 32-81 years) who underwent curative surgery for primary BC. Final
      pathology showed 4 (3.9%) with pT1a, 17 (16.7%) with pT1b, 44 (43.1%) with pT1c
      and 37 (36.3%) with pT2 breast carcinomas. The overall sensitivity of SSM was
      80.4%. An ANOVA showed significant (P<0.01) differences between the TBR of
      patients with G1 vs. G3 tumours, and between the TBR of those with G2 vs. G3
      breast carcinomas. Moreover, there was a difference (P=0.021) between the TBR of
      patients (n=12, 11.8%) with CEA serum levels >10 ng/ml (2.031+/-0.420), and those
      with normal (n=90, 88.2%) CEA values (1.713+/-0.446), whilst no difference (P=NS)
      was found between patients (n=27, 26.5%) with CA 15-3 >30 U/ml (1.893+/-0.401)
      and those with normal (n=75, 73.5%) CA 15-3 values (1.699+/-0.462). There was a
      mild inverse correlation between TBR and both the oestrogen (R=0.25, P=0.011) and
      the progesterone receptor (R=0.23, P=0.02) rate. The logistic regression analysis
      showed that only size and CA 15-3 serum levels represent true independent
      parameters, but the function was able to predict only 11 out of 21 (52.4%)
      patients with false-negative SSM. TBR is independent of age and mainly correlates
      with the size of the tumour. There are no reliable preoperative prognostic
      factors that are really useful for improving SSM sensitivity in patients with
      small breast carcinomas.

PMID- 15985370
TI  - Occult breast lesions: A comparison between radioguided occult lesion
      localisation (ROLL) vs. wire-guided lumpectomy (WGL).
AB  - Mammographic screening increases the number of impalpable breast cancers
      requiring surgical excision. It is important to optimise the localisation
      technique to remove the smallest amount of tissue, still adequately excising the
      lesion. The last 65 wire-guided lumpectomies (WGLs) were compared vs. the first
      65 radioguided occult lesion localisations (ROLLs) performed for impalpable
      breast cancers. Data collection included patient's age, radiological abnormality,
      pre-operative core biopsy, type of primary surgery, length of localisation and
      excision, hospital stay, cancer size, weight and volume of the excised specimen,
      clearance margins. All patients were successfully localised with ROLL and WGL.
      Localisation time was reduced with ROLL (P<0.001). Clear margins were achieved in
      83% ROLLs and 57% WGLs (P=0.001). Pathological cancer size and specimen weight
      were similar in both groups, although the specimen volume was slightly smaller
      for ROLL. A total of 74% ROLLs had excellent cosmetic outcomes and 26% good, vs.
      55% excellent and 45% good in WGLs. A larger amount of normal breast tissue was
      excised with WGL, without achieving any better cancer clearance. ROLL provides a
      feasible alternative to WGL. This quick and simple technique achieves an improved
      rate of clear margins.

PMID- 15985371
TI  - Voriconazole in the treatment of invasive fungal infections.
AB  - Fungal infections in immunocompromised patients in the Intensive Care Unit (ICU)
      are a major cause of mortality and morbidity and can lead to extended stays on
      the ICU. New antifungal drugs have been developed to increase treatment options
      to improve the clinical outcome. This article reviews the clinical efficacy, side
      effect profile, dosing and administration schedule of voriconazole, a recently
      launched second generation triazole. The article also discusses the warnings and
      precautions associated with the use of this drug. Voriconazole is an effective
      treatment option in the management of fungal infections.

PMID- 15985372
TI  - Semi-automated preparation of the dopamine transporter ligand [(18)F]FECNT for
      human PET imaging studies.
AB  - The fluorine-18 labeled dopamine transport (DAT) ligand 2 beta-carbomethoxy-3beta
      (4-chlorophenyl)-8-(2-fluoroethyl)nortropane (FECNT) has shown promising
      properties as an in vivo DAT imaging agent in human and monkey PET studies. A
      semi-automated synthesis has been developed to reliably produce [(18)F]FECNT in a
      16% decay corrected yield. This method utilizes a new [(18)F]fluoralkylating
      agent and provides high purity [(18)F]FECNT in a formulation suitable for human
      use.

PMID- 15985373
TI  - Classifying threats with a 14-MeV neutron interrogation system.
AB  - SeaPODDS (Sea Portable Drug Detection System) is a non-intrusive tool for
      detecting concealed threats in hidden compartments of maritime vessels. This
      system consists of an electronic neutron generator, a gamma-ray detector, a data
      acquisition computer, and a laptop computer user-interface. Although initially
      developed to detect narcotics, recent algorithm developments have shown that the
      system is capable of correctly classifying a threat into one of four distinct
      categories: narcotic, explosive, chemical weapon, or radiological dispersion
      device (RDD). Detection of narcotics, explosives, and chemical weapons is based
      on gamma-ray signatures unique to the chemical elements. Elements are identified
      by their characteristic prompt gamma-rays induced by fast and thermal neutrons.
      Detection of RDD is accomplished by detecting gamma-rays emitted by common
      radioisotopes and nuclear reactor fission products. The algorithm phenomenology
      for classifying threats into the proper categories is presented here.

PMID- 15985374
TI  - Iron salts in solid state and in frozen solutions as dosimeters for low
      irradiation temperatures.
AB  - The aim of this work is to study the irradiation of iron salts in solid state
      (heptahydrated ferrous sulfate) and in frozen acid solutions. The study is
      focused on finding their possible use as dosimeters for low temperature
      irradiations and high doses. The analysis of the samples was made by UV-visible
      and Mossbauer spectroscopies. The output signal was linear from 0 to 10 MGy for
      the solid samples, and 0-600 Gy for the frozen solutions. The obtained data is
      reproducible and easy to handle. For these reasons, heptahydrate iron sulfate is
      a suitable dosimeter for low temperature and high irradiation doses, in solid
      state, and in frozen solution.

PMID- 15985375
TI  - Preliminary results on the production of short-lived radioisotopes with a Plasma
      Focus device.
AB  - An experimental campaign was conducted to assess the feasibility of short-lived
      radioisotope (SLR) production within the pulsed discharges of a Plasma Focus (PF)
      device. This so-called "endogenous production" technique rests on the
      exploitation of nuclear reactions for the creation of SLR directly within the
      plasma, rather than on irradiating an external target. Until now only one
      research group has published data relevant to PF endogenous production of SLR,
      and the data seem to confirm that the PF has the capability to breed SLR. The
      campaign demonstrated production of (15)O, (17)F and (13)N from the
      (14)N(d,n)(15)O, (12)C(d,n)(13)N and (16)O(d,n)(17)F reactions. A 7kJ, 17kV
      Mather-type PF was operated with natural nitrogen, oxygen, CO(2) and deuterium in
      the vacuum chamber. Results to date confirm that, with a PF of this type, up to
      1microCi of SLRs per discharge can be obtained.

PMID- 15985376
TI  - Seizure freedom with different therapeutic regimens in intellectually disabled
      epileptic patients.
AB  - BACKGROUND: Epilepsy is a frequent condition in persons with intellectual
      disability and is more often difficult to treat than in the average population.
      Seizure freedom is the primary therapeutic goal which has important implications
      for the patient's quality of life. The aim of this study was to find out which
      antiepileptic therapy regimens (monotherapy or combination therapy) are effective
      in achieving this goal in intellectually disabled epilepsy patients. We were
      especially interested in the impact of the new antiepileptic drugs (AEDs) which
      were introduced during the past decade. METHOD: We investigated retrospectively
      the antiepileptic regimens on which the resident patients of a large epilepsy
      centre (as a rule with additional intellectual disabilities of different degrees)
      were seizure free in 2002. Information on antiepileptic medication and seizure
      frequency was taken out of the individual case documentation. It was also
      determined whether seizure free patients had already been seizure free in 1992.
      RESULTS: Two hundred and forty out of 675 patients (35,6%) with epilepsy were
      seizure free. The proportion of seizure freedom was 43,7% in patients with
      borderline intelligence, 39,2% in mild, 33,2% in moderate, 31,9% in severe, and
      21,9% in profound intellectual disability. One hundred and twenty-two (50,8%)
      seizure free patients were on monotherapy; 53 of them were on CBZ (PB: 34, VPA:
      25, PHT: 7, LTG: 3). Ninety-three patients (38,7%) were on duotherapies, CBZ/PB
      (27 patients), PB/PHT (17), and LTG/VPA (14) being the commonest. Of 18 (7,5%)
      triple therapies, LTG/PB/VPA (4 patients) was the commonest. Taken together, the
      five most frequent therapeutic regimens were CBZ monotherapy, PB monotherapy,
      CBZ/PB, VPA monotherapy and PB/PHT (a clear preponderance of classic AEDs). A
      distinction was made between "old seizure free" (seizure free already in 1992)
      and "new seizure free" (in 1992 still seizures) patients. In the 132 old seizure
      free patients the classic AEDs prevailed again, monotherapies with CBZ, PB and
      VPA being the most frequent regimens. In comparison, in the 78 new seizure free
      patients the novel combination LTG/VPA was the third most frequent, after the
      classic regimens CBZ/PB and CBZ; PB monotherapies were rare. CONCLUSION: In a
      majority of intellectually disabled patients with epilepsy (including those who
      became seizure free since 1992), complete seizure control has been achieved by
      monotherapy or duotherapy with classic AEDs. Of the new AEDs LTG in combination
      with VPA appears to be an important innovation.

PMID- 15985377
TI  - Prediction of VEGF mRNA antisense oligodeoxynucleotides by RNA structure software
      and their effects on HL60 and K562 cells.
AB  - Seven antisense oligodeoxynucleotides were selected using RNA structure 3.7
      software and the principle of low overall DeltaG (free energy). Their effects on
      cell growth, VEGF protein expression and apoptosis in HL60 and K562 leukemic
      cells were examined, and cell numbers and viability were assessed using trypan
      blue dye exclusion, MTT, ELISA and flow cytometry. The results showed that six of
      the seven antisense sequences inhibited the cell growth and down-regulated VEGF
      protein expression significantly. Endogenous VEGF plays an important role in the
      proliferation of HL60 and K562 leukemic cells. RNA structure software provides a
      rapid and efficient way of identifying effective antisense oligodeoxynucleotides.

PMID- 15985378
TI  - The response of primary articular chondrocytes to micrometric surface topography
      and sulphated hyaluronic acid-based matrices.
AB  - Understanding the response of chondrocytes to topographical cues and chemical
      patterns could provide invaluable information to advance the repair of chondral
      lesions. We studied the response of primary chondrocytes to nano- and micro
      grooved surfaces, and sulphated hyaluronic acid (HyalS). Cells were grown on
      grooves ranging from 80 nm to 9 microm in depth, and from 2 microm to 20 microm
      in width. Observations showed that the cells did not spread appreciably on any
      groove size, or alter morphology or F-actin organization, although cells showed
      accelerated movement on 750 nm deep grooves in comparison to flat surfaces. On
      chemical patterns, the cells migrated onto, and preferentially attached to, HyalS
      and showed a greater degree of spreading and F-actin re-arrangement. This study
      shows that 750 nm deep grooves and sulphated hyaluronic acid elicit responses
      from primary chondrocytes, and this could have implications for the future
      direction of cartilage reconstruction and orthopaedic treatments in general.

PMID- 15985379
TI  - Comparative clinical science: The medicine of the future.
AB  - This review explores the emergence of Comparative Medicine in the late 19th
      Century as 'the medicine of the future', its failure to realise these
      expectations during the 20th century as it became increasingly equated with
      laboratory animal models of human disease, and explains why there is now an
      unprecedented opportunity for this latent potential to be fully realised.
      Comparative medicine no longer rests on apparent similarities between disease
      mechanisms in different species but on the rapidly maturing ability to relate
      these similarities to a remarkably rich shared genetic heritage. In the United
      Kingdom, the creation of the new Medical Research Council Comparative Clinical
      Science Panel, once securely funded, will provide the infrastructure and
      strategic focus to foster comparative clinical research, encouraging
      collaboration between veterinary and human medicine and between investigators in
      institutes and in practice. This will generate the necessary evidence base for
      veterinary practice, raise the standard of veterinary research, broaden the
      horizons of human medicine and create real opportunities for veterinary surgeons
      to reconcile research with practice. The review explores the broad scope of the
      science which will flourish in this new environment and examines specific areas
      in greater depth as examples, notably multifactorial disease such as hypertension
      and diarrhoea, also aspects of comparative endocrinology and oncology, with
      emphasis on the growing power conferred by comparative molecular genetics.

PMID- 15985380
TI  - Effects of prey type on specific dynamic action, growth, and mass conversion
      efficiencies in the horned frog, Ceratophrys cranwelli.
AB  - To be most energetically profitable, predators should ingest prey with the
      maximal nutritional benefit while minimizing the cost of processing. Therefore,
      when determining the quality of prey items, both the cost of processing and
      nutritional content must be considered. Specific dynamic action (SDA), the
      increase in metabolic rate associated with feeding in animals, is a significant
      processing cost that represents the total cost of digestion and assimilation of
      nutrients from prey. We examined the effects of an invertebrate diet (earthworms)
      and a vertebrate diet (newborn mice) on mass conversion efficiencies, growth, and
      SDA in the Chacoan horned frog, Ceratophrys cranwelli. We found the earthworm
      diet to be significantly lower in lipid, protein, and energy content when
      compared to the diet of newborn mice. Growth and mass conversion efficiencies
      were significantly higher in frogs fed newborn mice. However, mean SDA did not
      differ between frogs fed the two diets, a finding that contradicts many studies
      that indicate SDA increases with the protein content of the meal. Together, our
      results indicate that future studies evaluating the effect of meal type on
      bioenergetics of herpetofauna are warranted and may provide significant insight
      into the underlying factors driving SDA.

PMID- 15985381
TI  - Regulation of the mammalian heart function by nitric oxide.
AB  - The mammalian heart expresses all three isoforms of nitric oxide synthases (NOS)
      in diverse cell types of the myocardium. Despite their apparent promiscuity, the
      NOS isoforms support specific signaling because of their subcellular
      compartmentation with colocalized effectors and limited diffusibility of NO in
      muscle cells. eNOS and nNOS sustain normal EC coupling and contribute to the
      early and late phases of the Frank-Starling mechanism of the heart. They also
      attenuate the beta1-/beta2-adrenergic increase in inotropy and chronotropy, and
      reinforce the pre- and post-synaptic vagal control of cardiac contraction. By
      doing so, the NOS protect the heart against excessive stimulation by
      catecholamines, just as an "endogenous beta-blocker". In the ischemic and failing
      myocardium, induced iNOS further reinforces this effect, as does eNOS coupled to
      overexpressed beta3-adrenoceptors. nNOS expression also increases in the aging
      and infarcted heart, but its role (compensatory or deleterious) is less clear. In
      addition to their direct regulation of contractility, the NOS modulate oxygen
      consumption, substrate utilization, sensitivity to apoptosis, hypertrophy and
      regenerative potential, all of which illustrate the pleiotropic effects of this
      radical on the cardiac cell biology.

PMID- 15985382
TI  - Effect of maximal dynamic exercise on exhaled ethane and carbon monoxide levels
      in human, equine, and canine athletes.
AB  - Exercise-induced oxidative stress (EIOS) refers to a condition where the balance
      of free radical production and antioxidant systems is disturbed during exercise
      in favour of pro-oxidant free radicals. Breath ethane is a product of free
      radical-mediated oxidation of cell membrane lipids and is considered to be a
      reliable marker of oxidative stress. The heatshock protein, haem oxygenase, is
      induced by oxidative stress and degrades haemoglobin to bilirubin, with
      concurrent production of carbon monoxide (CO). The aim of this study was to
      investigate the effect of maximal exercise on exhaled ethane and CO in human,
      canine, and equine athletes. Human athletes (n = 8) performed a maximal exercise
      test on a treadmill, and canine (n = 12) and equine (n = 11) athletes exercised
      at gallop on a sand racetrack. Breath samples were taken at regular intervals
      during exercise in the human athletes, and immediately before and after exercise
      in the canine and equine athletes. Breath samples were stored in gas-impermeable
      bags for analysis of ethane by laser spectroscopy, and CO was measured directly
      using an electrochemical CO monitor. Maximal exercise was associated with
      significant increases in exhaled ethane in the human, equine, and canine
      athletes. Decreased concentrations of exhaled CO were detected after maximal
      exercise in the human athletes, but CO was rarely detectable in the canine and
      equine athletes. The ethane breath test allows non-invasive and real-time
      detection of oxidative stress, and this method will facilitate further
      investigation of the processes mediating EIOS in human and animal athletes.

PMID- 15985383
TI  - Magnetic micro- and nanoparticle mediated activation of mechanosensitive ion
      channels.
AB  - Most cells are known to respond to mechanical cues, which initiate biochemical
      signalling pathways and play a role in cell membrane electrodynamics. These cues
      can be transduced either via direct activation of mechanosensitive (MS) ion
      channels or through deformation of the cell membrane and cytoskeleton.
      Investigation of the function and role of these ion channels is a fertile area of
      research and studies aimed at characterizing and understanding the mechanoactive
      regions of these channels and how they interact with the cytoskeleton are
      fundamental to discovering the specific role that mechanical cues play in cells.
      In this review, we will focus on novel techniques, which use magnetic micro- and
      nanoparticles coupled to external applied magnetic fields for activating and
      investigating MS ion channels and cytoskeletal mechanics.

PMID- 15985384
TI  - Characterization of mouse glandular kallikrein 24 expressed in testicular Leydig
      cells.
AB  - Mouse kallikrein 24 is thought to encode a functional serine protease belonging
      to the mouse glandular kallikrein gene family. Preliminary results suggest that
      this kallikrein may play a role in testis function in adult mice. In order to
      obtain insights into its physiological functions, we undertook molecular and
      biochemical analyses of this enzyme. We cloned a cDNA for kallikrein 24 from the
      adult mouse testis cDNA library. Kallikrein 24 was expressed in the kidney,
      submandibular glands, ovary, epididymis, and testis of the mouse. In the testis,
      kallikrein 24 mRNA was detectable at 4 weeks of postnatal development, and became
      more prominent thereafter. The kallikrein 24 gene was expressed exclusively in
      the Leydig cells of adult mice. When Leydig cells isolated from a 2-week-old
      mouse testis were cultured in the presence of testosterone, kallikrein 24
      expression was induced. Active recombinant enzyme showed trypsin-like
      specificity, favorably cleaving Arg-X bonds of synthetic peptide substrates. The
      enzymatic activity was strongly inhibited by typical serine protease inhibitors.
      Mouse kallikrein 24 degraded casein, gelatin, fibronectin and laminin. These
      results suggest that the enzyme may play a role in the degradation of
      extracellular matrix proteins in the interstitial area surrounding the Leydig
      cells of the adult mouse testis. The present findings should contribute to future
      physiological studies of this mouse testis protease.

PMID- 15985385
TI  - Determinants of physician use of an ambulatory prescription expert system.
AB  - PURPOSE: To determine whether physician experience with and attitude towards
      computers is associated with adoption of a voluntary ambulatory prescription
      writing expert system. METHODS: A prescription expert system was implemented in
      an academic internal medicine residency training clinic and physician utilization
      was tracked electronically. A physician attitude and behavior survey (response
      rate=89%) was conducted six months after implementation. RESULTS: There was wide
      variability in system adoption and degree of usage, though 72% of physicians
      reported predominant usage (> or =50% of prescriptions) of the expert system six
      months after implementation. Self-reported and measured technology usage were
      strongly correlated (r=0.70, p<0.0001). Variation in use was strongly associated
      with physician attitude toward issues of system efficiency and effect on quality,
      but not with prior computer experience, level of training, or satisfaction with
      their primary care practice. Non-adopters felt that electronic prescribing was
      more time consuming and also more likely to believe that their patients preferred
      hand-written prescriptions. CONCLUSION: A voluntary electronic prescription
      system was readily adopted by a majority of physicians who believed it would have
      a positive impact on the quality and efficiency of care. However, dissatisfaction
      with system capabilities among both adopters and non-adopters suggests the
      importance of user education and expectation management following system
      selection.

PMID- 15985386
TI  - Parvovirus B19 viral loads in relation to VP1 and VP2 antibody responses in
      diagnostic blood samples.
AB  - BACKGROUND: Human parvovirus B19 infection is characterised by high peak viral
      load levels followed by episodes of prolonged viremia. The risk of transmission
      of parvovirus B19 by blood or blood products has been increasingly recognised and
      parameters that can predict the risk of transmission are subject of interest.
      OBJECTIVES: This study aimed to study correlations between B19 viral DNA loads
      and antibody responses to the viral antigens VP1 and VP2 in clinical serum
      samples. STUDY DESIGN: A panel of 1610 serum samples from patients clinically
      suspected from acute B19 infection were analysed. Antibodies were measured by the
      parvovirus anti-VP1 immuno-fluorescence assay (IFA) and the anti-VP2 enzyme
      immunoassay (EIA) from Biotrin. B19 viral loads were measured by a real-time PCR
      using the external WHO standard for DNA quantification. RESULTS: Positive IgM
      responses were found in 154 (9.6%) of the 1610 sera tested. Based on the PCR
      results in a subset of 312 sera, the anti-VP2 EIA IgM showed a better combination
      of sensitivity/specificity (91%/94%) compared to the anti-VP1 IFA (66%/97%). B19
      DNA levels in the sera strongly correlated with the levels of IgM antibodies, all
      sera with high viral loads (>10(6)IU/ml) having VP2 EIA IgM ratios above 3.0.
      CONCLUSIONS: The B19 VP2 IgM ELISA is superior to the B19 VP1 IgM IFA if verified
      by PCR. Anti-VP2 IgM antibodies in sera are indicative for the presence B19 DNA
      and can be used to predict high levels of B19 DNA in diagnostic sera.

PMID- 15985387
TI  - Dobutamine stress echocardiography and cardiac troponin T for the detection of
      significant coronary artery disease and predicting outcome in renal transplant
      candidates.
AB  - AIMS: Ischaemic heart disease is the leading cause of mortality and morbidity in
      patients with end-stage renal disease (ESRD) and after renal transplantation.
      However, the optimal non-invasive test for coronary artery disease (CAD)
      diagnosis in this population has yet to be established. The aim of this study was
      to assess the diagnostic accuracy of dobutamine stress echocardiography (DSE) and
      baseline plasma cardiac troponin T (cTnT) for detecting significant CAD and
      predicting adverse cardiac events in patients referred for renal transplantation.
      METHODS: Coronary angiography, DSE, and baseline cTnT measurements were performed
      in 118 consecutive patients (mean age 52+/-12 years, 75 male) with ESRD (mean
      creatinine 608+/-272 micromol/L) referred for renal transplantation. The mean
      follow-up period was 1.32+/-0.48 years. Significant CAD was defined as a
      reduction in luminal diameter >70% by visual estimation in at least one major
      epicardial vessel. An abnormal DSE result defined as the development of a new
      regional wall motion abnormality in one or more normal resting segments or a
      deterioration of wall motion in one or more resting hypokinetic segments. A
      baseline cTnT>0.1 microg/L was taken as positive. RESULTS: Significant CAD in at
      least one vessel was present in 35 patients (30%). The number of patients with
      significant 3 vessel and 2 vessel disease was 6 and 7, respectively. An abnormal
      DSE result was present in 36 (31%) patients. Thirty-one (26%) had cTnT>0.1
      microg/L. Sixty-four (54%) patients were on dialysis and 46 (39%) were diabetic.
      The sensitivity, specificity, positive and negative predictive values for DSE in
      detecting significant coronary artery disease were 88%, 94%, 86% and 95%,
      respectively. The same values for a raised cTnT were 54%, 62%, 40% and 74%,
      respectively. The combination of an abnormal DSE result and raised cTnT gave
      values of 61%, 91%, 76%, and 80%, respectively. Over the follow-up period,
      mortality was significantly higher in those with a raised baseline cTnT but not
      those with an abnormal DSE result or significant CAD. CONCLUSION: DSE is an
      accurate technique for the detection of significant CAD in renal transplant
      candidates. An elevated cTnT does not predict significant CAD in this population
      and when used in conjunction with DSE, reduces the sensitivity of the combined
      tests. cTnT is an important marker of prognosis in renal transplant candidates.

PMID- 15985388
TI  - Error-prone repair and translesion synthesis III: the activation of UmuD (or less
      is more).
AB  - Following DNA damage to Escherichia coli bacteria, RecA protein is activated by
      binding to single stranded DNA and cleaves its own gene repressor (LexA protein).
      Two papers from Graham Walker's laboratory showed that several bacterial genes in
      addition to RecA are repressed by the LexA repressor and are inducible following
      DNA damage [C.J. Keyon, G.C. Walker, DNA-damaging agents stimulate gene
      expression at specific loci in Escherichia coli, in: Proceedings of the National
      Academy of Sciences of the United States of America 77, 1980, pp. 2819--2823] and
      predicted that one of them (UmuD) might itself be subject to activation by a
      further cleavage reaction involving activated RecA protein [K.L. Perry, S.J.
      Elledge, B.B. Mitchell, L. Marsh, G.C. Walker, umuD,C and mucA,B operans whose
      products are required for UV light- and chemical-induced mutagenesis: UmuD, MucA,
      and LexA proteins share homology, in: Proceedings of the National Academy of
      Sciences of the United States of America 82, 1985, pp. 4331--4335]. The processed
      form of UmuD, termed UmuD', later proved to be a subunit of DNA polymerase V, a
      key enzyme involved in translesion synthesis.

PMID- 15985389
TI  - The analysis of thiamin and its derivatives in whole blood samples under high pH
      conditions of the mobile phase.
AB  - In this study a protocol for the analysis of thiamin and thiamin coenzymes in
      whole blood was developed. Thiamin and its coenzymes are analyzed by reversed
      phase liquid chromatography (RPLC), precolumn derivatisation with alkaline
      potassium ferricyanide and fluorescence detection, all at pH 10. Under these
      relatively high pH conditions the detectability of the analytes and the
      robustness of the method were substantially improved. The use of a high pH
      resistant RPLC column was a crucial step in developing this analysis method.
      Reproducibility, linearity, recovery, detection limit and column robustness were
      investigated. The within-batch CV was <2.5%, the between-batch CV <4.5%. The
      method was linear far above the physiological relevant concentration level.
      Recovery was almost 100% on an average. The limit of quantification was 1 nmol/l.
      The robustness of the RPLC column proved to be very high. Up to 1500 injections
      hardly any substantial changes in retention times and efficiency were observed.
      In summary: Using a high pH resistant RPLC column resulted in a robust, sensitive
      and precise method for the analysis of total Vitamin B1 and especially of TDP.

PMID- 15985390
TI  - Imaging of fetal cerebral ventriculomegaly: a guide to management and outcome.
AB  - Ultrasound imaging is the screening modality of choice for initial evaluation of
      the fetal central nervous system. However, there are times when fast magnetic
      resonance imaging (MRI) provides information additional to that available from
      ultrasound. This review will: (1) discuss the ultrasound evaluation of
      ventriculomegaly and its associated anomalies; (2) illustrate and expand upon the
      type of additional information MRI can provide beyond that which is available
      from ultrasound; and (3) discuss how this additional information can alter
      diagnosis as well as change maternal counselling and case management.

PMID- 15985391
TI  - Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional
      autopsy?
AB  - Fetal and perinatal autopsy provides essential diagnostic information not only
      for parents but also for medical audit and clinical trials. The autopsy rate is
      decreasing throughout the world for numerous reasons. Medical imaging has always
      been part of the autopsy process, but in the last decade there has been increased
      interest in imaging as additional to or a replacement for autopsy. This is
      especially so with the wider availability of magnetic resonance (MR) scanners
      that are able to provide detailed anatomy of all body structures as well as
      having the potential to provide information about histopathological patterns of
      injury. Postmortem MR imaging (MRI) provides similar information to autopsy for
      gross pathology of most organ systems. It often provides more information in
      cases of central nervous system abnormalities, but is less accurate for cardiac
      abnormalities. Targeted, image-guided biopsy may allow histological diagnosis
      following postmortem MRI.

PMID- 15985392
TI  - MRI of fetal and neonatal cerebellar development.
AB  - In the last few years magnetic resonance imaging (MRI) has expanded its
      diagnostic capability in the evaluation of fetal brain. Starting from the 18th to
      20th gestational weeks, MRI can reliably depict fetal brain anatomy and locate
      pathology, offering a robust and reliable tool for the assessment of disorders of
      the fetal central nervous system. In this review quantitative and qualitative in
      vivo MRI data on fetal cerebellar development are presented. Our normative
      reference data have been obtained from a database of 580 MR fetal imaging
      studies. Normal cases were selected within normal MRI fetal brain studies, and
      all selected cases had a normal clinical evaluation and a normal cranial
      ultrasound or MR image after birth. Fetal cerebellar development is gradual,
      steady, and grossly comparable to the development of the supratentorial brain.
      Archicerebellar (flocculonodular lobe) and paleocerebellar (vermis) structures
      develop before the neocerebellum (cerebellar hemispheres) that develops more
      slowly and largely after birth.

PMID- 15985393
TI  - [Study of Five STR Loci in A Chinese Han Population.].
AB  - To understanding the allele structure and genetic polymorphisms at five STR loci
      in Chinese Han population, and construct a preliminary database, EDTA-blood
      specimens were collected from unrelated individuals. DNA samples were extracted
      with Chelex method and were amplified by PCR technique. The PCR products were
      analyzed using both PAGE horizontal electrophoresis with discontinuous buffer
      system and automated fluorescence detection approach. As a result, three STRs
      consist of simple repeat motifs, while two STR contain a complex repeat
      structure. The STR polymorphisms at all of the five loci have been observed in
      Chinese Han population. In a word, the obtained data are beneficial to
      understanding the population genetics of the five STR loci in Chinese Han
      population. As a simple approach, the PAGE horizontal electrophoresis can be
      employed for typing the five STR markers.

PMID- 15985394
TI  - [The paternal origin of an extra chromosome 13 from the patient with patau
      syndrome.].
AB  - A boy was born at 38 week's gestation by Cesarean delivery . Affected newborn was
      characteristically bilateral cleft lip and severe cleft palate. The sternum was
      malformation. The sacrospinal bifida and the talipes varus were found and the
      testes were not descended. The boy died after delivery within 10 minutes owing to
      respiratory failure. Cytogenetic analysis of his peripheral lymphocyte by G
      banding showed a karyotype 47,XY,+13 , which was also confirmed by fluorescence
      in situ hybridization (FISH). The locus D13S317 was detected by the peripheral
      blood from the boy and the parents. Three alleles were found from the boy in
      locus D13S317 and two from the father. The extra chromosome 13 was from the
      nondisjunction during the first meiotic division of the father.

PMID- 15985395
TI  - [Relationship Between Molecular Marker of Western Main Pig H-FABP Gene and IMF
      Content.].
AB  - By using 265 pigs from eight breeds including Duroc,Landrace,Large
      White,Neijiang,Rongchang,Hanjiang Black,Hanzhong White,Bamei and wild ones, the
      genetic variations of 5'-upstream region from and the second intron in porcine H
      FABP gene were checked by PCR-RFLP molecular marker with HinfI, Hae III and
      MspI,and effect of H-FABP gene on IMF content was then analyzed by least square
      analysis.The results showed as follows:(1) 8 pig breeds and wild pig had
      polymorphism at Hinf I-RFLP site. In above detected breeds,large white,Bamei pig,
      Hanjiang Black,Hanzhong White pig breeds and wild pig presented low polymorphism
      while other breeds have mediate polymorphism;(2)Among the tested breeds only 4
      Chinese local pig breeds had no polymorphism at the Hae III-RFLP and Msp I-RFLP
      sites,but Duroc,Landrace,Largewhite, Hanzhong White pig breeds and wild pig had
      polymorphism. Wild pig at the Hae III-RFLP , Landrace,Largewhite and wild pig at
      the Hae III-RFLP and Msp I-RFLP sites were low polymorphism,others were mediate
      polymorphism;(3) H-FABP gene increased IMF content significantly(p0.05). Genetic
      effect of H-FABP gene on IMF content were HH>Hh>hh,DD.

PMID- 15985396
TI  - [Molecular Cloning of Smooth Muscle Calponin h1 in SHeep.].
AB  - It was found that the level of Calponin h1 (CaP h1) mRNA was significantly up
      regulated by Estrogen in the myometrium of sheep towards the end pregnancy.
      Although the CaP h1 has been widely used as a reference gene to observe the
      changes of expression level of other genes, the full-length gene in sheep has not
      been obtained. With the oligo nucleotide primers according to human, mouse and
      pig CaP h1 mRNA, the full-length cDNA of CaP h1 was cloned by 5'- and 3'-RACE
      (Genbank accession number = AY327118). The cDNA was 1499bp in length and
      contained a complete open reading frame of 891 bp, encoding a protein of 297
      amino acid residues. 5'-and 3'-UTR was 79 bp and 529bp, respectively. With PCR
      SSP approaches,the genomic DNA of sheep CaP h1 was obtained .It showed that the
      gene has 7 exons and 6 introns, spanning over 8kb(Genbank accession number of
      introns : AY771807,AY771808, AY771809, AY771810.) Homologous comparison indicated
      that the cDNA sequences are highly conserved across the species. The highest
      homology was found in wild pig (92%), followed by human (88%), rat (81%), mouse
      (81%) and chicken (79%). The intron sequence and length showed a large variation
      among species (>50%).

PMID- 15985397
TI  - [Polymorphism Analysis of the CSN1S2 Gene Digested.].
AB  - PCR-RFLP was applied to analyze the polymorphism of CSN1S2 gene in 170 goats that
      comprised of five goat breeds, namely Xinong Saanen dairy goat, Guanzhong dairy
      goat, Shaannan white goat, Angora goat and Boer goat. A 310 bp -long PCR product
      was digested with Alw26I and demonstrated polymorphism in five goat populations
      that were all at Hardy-Weinberg equilibrium (P>0.05). For Xinong Saanen dairy
      goat, Guanzhong dairy goat, Shaannan white goat, Angora goat and Boer goat, gene
      heterozygosity/effective allele gene number/Shaanon information entropy
      /Polymorphism information content were 0.1589/1.1889/0.2955/0.1463,
      0.4114/1.6981/0.6017/0.5171, 0.1653/1.1980/0.3046/0.1516, 0646/1.0691/0.1463/
      0.0625, 0.0541/1.0572/0.1270/ 0.0526, respectively. According to the heredity
      diversity indexes described above of the five goat breeds, Guanzhong dairy goat
      had the most abundant heredity diversity and showed high polymorphism, and Xinong
      Saanen dairy goat and Shaannan white goat were inferior, while Angora goat and
      Boer goat had the lowest genetic variability.

PMID- 15985398
TI  - [Generation of Chicken Germ-line Chimeras by Transferring PGCs and Their
      Identification by AFLP.].
AB  - PGCs (Primordial germ cells) were isolated from the blood of 51~56 h hatching
      Shiqiza chicken embryos by Ficoll density gradient centrifugation. The PGCs were
      injected into 2.5 d hatching embryos of H breed chicken to produce germ-line
      chimeras. AFLP checking method was established to identify chicken germline
      chimeras. Eight germ-line H-S chimera embryos were identified among 20 developing
      H breed embryos.

PMID- 15985399
TI  - [Pridiction of the Sex-effects of the Cocoon Quality Characters in Silkworm.].
AB  - In this paper , the sex-effects of the cocoon quality characters in silkworm was
      predicted with Mixed linear model uThe fact that the probability of effect
      variance and predictability of random gender of whole cocoon weight, cocoon shell
      weight, ratio of cocoon shell and pupa weight reached a level of extreme
      significance showed that the gender effect of the four traits was extremely
      significant, which matched with the reality completely. The predictive values of
      gender effect of the four traits of female(male) were 0.248g (-0.247g), 2.423cg(
      2.394)cg, -1.976%(1.992%) and 0.224g(-0.223g) respectively. Each trait showed
      single peak distribution after adjusting by sex-effects, which fitted for the
      request that quantitative traits should show continuously normal standard
      distribution if QTL analysis was taken.

PMID- 15985400
TI  - [RAPD Identification of Three Types of Three-lines Hybrid Rice with Defferent
      Male Sterile Cytoplasms and Their Parent Lines.].
AB  - The RAPD analysis was conducted on genome DNA from 21 sets of rice, including 6
      three-line hybrid rice combinations, separately derived from three different
      kinds of cytoplasmic male sterile (CMS) lines and their related parents. Out of
      264 random primers screened first, 25 primers displayed well in polymorphisms. It
      was shown that only 7 bands amplified respectively from 7 primers were enough to
      discriminate the different types of CMS, the hybrid combinations and their
      parents.

PMID- 15985401
TI  - [Isolation and Sequence Analysis of the Xa21 Gene Wxon II Homologus from
      Different Species of Wild Rice in Yunnan.].
AB  - The Xa21 gene previously cloned from the wild rice species Oryzae longistaminata
      confers broad-spectrum resistance to rice leaf blight caused by different strains
      of Xanthomonas oryzae pv. oryzae. Here we attempted to determine the existence of
      Xa21 homologs in other wild rice species and rice cultivars and the sequence
      differences between the homologs. We synthesized specific primers based on the
      reported Xa21 sequence to amplify homologs of the gene exon II from several rice
      cultivars and three wild rice species in Yunnan Province, China. The fragments
      cloned from various types of O. rufipogon Griff from Jinghong and Yuanjiang,
      Yunnan Province, were highly homologous to the reported Xa21 gene exon II.
      However, the fragment was not found in O. officinalis Wall. and O. meyeriana
      Baill. Sequence analysis suggested that differences in nucleotides were located
      randomly in the fragments we cloned.

PMID- 15985402
TI  - [Heredity analysis of main characters of nitrogen use efficiency in maize.].
AB  - With P1, P2, F1, F2, B1 and B2 generations of two combinations of maize with high
      nitrogen use efficiency, hereditary capacity and genetic progress of seventeen
      characters were studied. The random block design was used in the experiment. The
      results showed that the heritability of each traits was different at different N
      levels. Broad heritability was between 0.78 and 0.46, and narrow heritability
      between 0.68 and 0.23 at low N level treatment. Broad heritability was between
      0.76 and 0.49, narrow heritability between 0.67 and 0.25 at high N level
      treatment. The heritability of the chlorophyll content of ear leaf at heading
      stage period, NUE, ear weight and area of ear leaf were higher than other major
      characters at low N, the hereditary capacity of the biomass at heading stage
      period, ear weight, chlorophyll content of ear leaf at heading stage period and
      biomass at maturity were higher than other major characters at high N. These
      characters could be selected at early generation at low and high N, respectively.

PMID- 15985403
TI  - [Genetic diversity analysis of alfalfa floral properties.].
AB  - Genetic mutations of alfalfa floral properties,including calyx diameter, coronary
      length, flower number per raceme, raceme number per twig, flower number per unit
      area, percentage of flicked flowers, excreted nectar volume, sugar concentration
      in nectar and contents of sucrose, fructose and glucose in nectar,have been
      studied with both morphological markers and RAPD markers. The results showed that
      the genetic variation of floral properties is from 0.80% to 92.30%, of which the
      content of glucose was the most significant one with the variation from 0.01 to
      0.53 mumol/L (p0.05), and the sugar concentration was the most insignificant one
      (P>0.05). RAPD analysis showed that variances of genetic distances was from 0.21
      to 0.35, among which the most significant one was WL323 and Shanbei, and the most
      insignificant one was Derby and Prime. Thus it can be seen that genetic diversity
      of floral properties among these varieties of alfalfas is abundant.

PMID- 15985404
TI  - [Cloning and Evolutionary Analysis of Homologous Sequences of CYP86MF Gene in
      Cruciferae.].
AB  - In order to direct the construction of plant germplasms by elucidating the
      relatives among plants at the level of gene, CYP86MF gene analogues from 11
      species of 6 genera in Cuciferae were respectively obtained by PCR strategy using
      gene specific primers designed from conserved regions of CYP86MF gene reported.
      Sequence comparisonindicated that the similarities among the genes at nucleotide
      level were over 80%, and the similarities at amino acid level remained above 70%.
      The differences between the genes at nucleotide and amino acid level between
      species were 1.0% ~ 5.7% and 2.6% ~ 7.3% respectively, while those between genera
      5.6% ~ 22.5% and 7.3% ~ 31.2%, respectively. Phylogenetic analysis showed that
      Brassica was closely related to Raphanus, followed by Rorippa Scop, Arabidopsis
      Heynh, Capsella Medic orderly, most distantly related to Orychophrogmus. It was
      concluded that CYP86MF gene was not applicable to specie and subspecie taxon but
      genus taxon because the differences of sequences in nucleotides and amino acids
      were lower between species than genera.

PMID- 15985405
TI  - [Establishment of Genic Male Sterile Lines of Brassica napus by Wide Cross and
      Their Cytology and Morphology.].
AB  - One and three male sterile plants were found in the progenies of the intergeneric
      hybrids by crossing Brassica napus and Brassica juncea to Orychophragmus
      violaceus, respectively. After interspecific cross and full-sib crosses, four
      genic male sterile lines were obtained. The results of cytological observations
      indicated that somatic chromosome number was 38 in all types of sterile lines,
      which were considered as the type of B. napus. Most of pollen mother cells (PMC)
      in all sterile plants were observed normally for chromosome behaviour. But
      abnormal phenomena of chromosome, which present for chromosome lagging and
      bridge, were still found at each stage of meiosis in these sterile lines. These
      lines belonged to complete sterile type. There were distinct differences between
      sterile plants and normal plants in the flower morphology. Bud death at different
      degrees was found on anthotaxies in sterile plants. Studies on the flower growth
      showed that the growths of the pistils in sterile plants were gradually
      accelerated along with pollen sterility. At the same time there were two slowly
      growth stages of the pistils growth in normal plants. The prospects of these
      sterile lines were discussed in this paper.

PMID- 15985406
TI  - [Development of EST (Expressed Sequence Tags) Marker in Chinese Cabbage and its
      Transferability to Repeseed.].
AB  - 28 pairs of primers were designed according to the expressed sequence tags in
      Chinese cabbage. After testing on the annealing temperature and the concentration
      of primer, dNTP and MgCl2, a suitable PCR system was established. Under the
      condition of reaction system developed, primers designed specific to ESTs were
      screened against genomic DNA of inbreed line A from which the cDNA library was
      constructed. Among them, 18 pairs of primers showed the amplification. Then all
      the primers available in line A were subjected to PCR for DNAs from 17 cabbage
      varieties. Polymorphism was detected by electrophoresis with agarose gel, and 10
      of 18 primer sets could reveal polymorphisms among cabbage varieties, which
      accounted for 55.6% of primers selected. To examine the transferability of EST
      markers developed in cabbage, all primers were further used for PCR-mediated
      amplification of genomic DNA from different varieties of rapeseeds. Of 28 pairs
      of primers, 24 were able to produce amplified product(s) and 18 showed
      polymorphisms, accounting for 85.7% and 64.3% of total primers respectively. All
      of 18 primer sets that amplified in cabbage also showed amplified products in
      rapeseed and 13 of them were polymorphic. Even amongst the 10 primer sets that
      were unable to amplify in cabbage, 6 pairs produced amplification and 5 could
      reveal the polymorphism in rapeseeds. Results obtained in the present paper
      proved that developing polymorphic markers based on EST could be feasible and
      this kind of marker would be transferable to closed related species.

PMID- 15985407
TI  - [Cloning, Characterization and Expression Vector Construction of Potato Proteas
      inhibitor II Gene (PIN II-2x) from Diploid Potato (Solanum phurejia).].
AB  - Based on the published gene sequence of tetraploid potato (Solanum.tuberosum)
      protease-inhibitor II, a genomic DNA and a cDNA sequence of potato protease
      inhibitor II gene were obtained from the cDNA library and the genomic DNA of a
      diploid potato IVP101 (Solanum.phurejia) using PCR method and named PINII-2x.
      Nucleotide sequencing confirmed that the full-length DNA of PINII-2x was 580 bp,
      including an 115 bp intron and two exons. cDNA was 462 bp ( stop codon TGA not
      included) and had 88% similarity to the tetraploid potato protease-inhibitor II.
      The PINII-2x open reading frame encodes a 154-amino acid polypeptide with a
      predicated size of 16.6 KD and a calculated PI of 6.08. The deduced proteins from
      PINII-2x cDNA had 93% homology with other tetraploid potato protease-inhibitor
      II, which contain the intact signal peptide and two active site similar to the
      potato protease-inhibitor II family. Test of the RT-PCR indicated that PINII-2x
      mRNA is wound- induced expression in potato leaves. Binary vector of PINII-2x
      cDNA drove by either rice Actin I promoter (ActI) or maize Ubiquitin promoter
      (Ubi) was constructed.

PMID- 15985408
TI  - [Preparation and Regeneration of Protoplasts from Monascus purpureus and Genetic
      Transformation System.].
AB  - Generation of fungal protoplast is an essential tool for genetic transformation
      system. To establish protoplast-mediated genetic transformation system of
      Monascus purpureus, conditions for the protoplast isolation and regeneration of
      the mycelia of various enzymes and osmotic stabilizers were examined. To
      investigate suitable cell age for the protoplast preparation of mycelia of M.
      purpureus, the mycelia were cultured in different ways at 30oC. Mycelia obtained
      through cellophane - mediated culture for 30~40h were adequate to protoplast
      preparation. When lysing enzyme, cellulase and snailase were added to the mycelia
      in combination or alone, combination of lysing enzyme, cellulase and snailase
      accordingly at the concentration of 0.3%, 0.1% and 1% was most benefit for
      protoplast yield. When we applied various osmotic stabilizers at different
      concentrations to protoplast preparation, 1 mol/L MgSO4 was most effective for
      the protoplast release. The suitable incubation time with enzyme for the maximum
      release of protoplasts was 2.5-hr. When we investigate various osmotic
      stabilizers for the regeneration of the protoplasts of mycelia of strain M34 and
      N18, the complete medium containing 0.6 mol/L sucrose induced highest hyphal
      growth with regeneration frequency of 8.5% and 36.4%, respectively. PEG and CaCl2
      mediated protoplast co-transformation of strain M34 with pBC-Hygro and pNL1,
      hygromycin B as selective marker, was fulfilled and 100 stable transformants per
      microgram DNA were obtained.

PMID- 15985409
TI  - [Preliminary Studies on the Relationship Between Meiosis of Pollen Mother Cells
      and Pollen Abortion of Aloe arboresense Mill.].
AB  - The main reason for pollen abortion in Aloe arboresens Mill. was studied through
      the observation of meiosis and the microspore development of its pollen mother
      cells(PMCs). There are 14 chromosomes in the PMC of Aloe arboresens Mill.,
      containing four pairs of long chromosomes and three pairs of short ones, and this
      karyotype belongs to dichotocarpism. Abnormalities observed were fallen into four
      categories:(1) Univalents, they were caused by failure in pairing, asynapsis and
      precocious cancellation of terminal chiasma. Oriented univalent pair was
      distributed at two poles normally in anaphase, while non-oriented univalent pair
      only at one pole. Another factor leading to univalents was that chromosomes were
      paired but without substantial exchange. (2) Multivalents. They might be produced
      by translocation heterozygote.(3) Chromosome bridges. There were three kinds of
      bridges in anaphase I and anaphase II: single and double chromosome bridge as
      well as "diagonal bridge".(4) A few cells were found with lagged chromosomes,
      micronuclei and unbalanced segregation of the chromosomes. In the later stages of
      meiosis, well-spread chromosomal configurations were rare because of the
      extremely sticky nature of the chromosome. The number and ratio of abnormalities
      were analysed and the relationship between abnormalities and pollen sterility
      were discussed. It is concluded that the sticky nature of the chromosome is the
      main reason for abnormal meiosis of Aloe arboresens Mill.PMC and pollen
      sterility. More than 90% of matured pollen grains were sterile.

PMID- 15985410
TI  - [Identification of Regulatory Sequence of lip Genes of Phanerochaete
      chrysosporium under Lignin-degradation.].
AB  - Eleven subcloned DNA fragments from the 5'- upstream region of lipA, lipC and
      lipF of Phanerochaete chrysosporium were assayed by using the gel mobility shift
      assay(GMSA). The total proteins extracted from P.chrysosporium mycelia grown in
      Kirk medium and natural fir wood chip were used to identify the segments in these
      11 DNA fragments which are controlled by some regulatory proteins. The results
      showed that two DNA segments LG2P3(396bp) and LG6S1-2 (738bp) in the 5'-noncoding
      regions of lipC and lipF were able to specifically bind total mycelial proteins
      of P. chrysosporium incubated in Kirk medium, separately. One DNA segment LG6S2
      (226bp) from the 5'-noncoding region of lipF was found to specifically bind total
      mycelial proteins of this fungus on natural fir wood chip. Analysis of the
      sequences showed that there were many cis-regulatory elements in these DNA
      segments, implying that these sequences may be bound by some transcriptional
      regulation protein factors.

PMID- 15985411
TI  - [Three steps for amplifying quick evolving region of DNA.].
AB  - A common problem in research of molecular evolution is difficult to efficiently
      amplify quick evolving target sequence of genes in different species or genus
      using specific primers, thus making experimental process and final analysis of
      total results delayed. Although using nested or semi-nested PCR can prominently
      increase PCR specificity, it really cannot efficiently amplify quick evolving
      region of DNA in our research of gene Fak56D. In this research, we need PCR
      products corresponding to gene Fak56D of different species of Drosophila
      melanogaster or other genus of Drosophila . For the high evolutionary rate,most
      materials did not produce qualified PCR products. To solve this problem, we
      initially used a combination method of three steps, i.e. semi-nested PCR taken
      together with orientational gel extraction, which satisfactorily met the demands
      of next cloning and sequencing steps.

PMID- 15985412
TI  - [Establishment of Immortal Lymphoblastoid Cell Lines of Non-syndromic Deafness
      Family and Several Methods fro Transforming Human B Lyphocyte by EB virus.].
AB  - Reservation of rare family materials is the base for us to do further research.
      Family of Jiang-Su Huai-Yin is one of the biggest non-syndromic deafness families
      in the world. In this family,deafness is maternally inherited and all the
      sufferers have the mitochondrial DNA 12s RNA A1555G mutation. Four methods are
      used in the experiments for establishing immortal lymphoblastoid cell lines of
      the family with non-syndromic deafness. Results were as follows: 1 cell line was
      from small amout of whole blood method, 1 cell line from frozen whole blood
      method, 14 cell lines from frozen leukocyte method, and 36 cell lines from
      cyclosporin A method. In this paper, we will discuss these four methods through
      our experiments of establishing cell lines.

PMID- 15985413
TI  - [Construction, Expression, Purification and Antiviral Activity of Fused
      Interferon-BLA (IFN-BLA).].
AB  - A fusion protein, Interferon-BLA (IFN-BLA), was constructed with IFN-beta-1b and
      IFN-alpha-2b separating by a linker -GGGS-. The laboratory-scale expression
      conditions in E.coli BL21 CodonPlus (DE3)-RIL had been optimized and IFN-BLA was
      expressed higher than 35% of total protein in the cells mainly as inclusion body.
      The inclusion body of IFN-BLA was denatured and refolded by dialysis and purified
      by ion-exchange chromatography. The overall yield of IFN-BLA was about 45 mg/L
      with purity higher than 90%. Antiviral activity assay suggested that this newly
      fused protein may have synergetic or additive antiviral activities.

PMID- 15985414
TI  - [A Novel Method for Increasing the Number of Metaphase Cells Cultured in vitro.].
AB  - To increase the number of metaphase cells cultured in vitro, two bovine
      fibroblast cell lines (YFF and CNF) were frozen at 4 degrees for different length
      of time prior to colchicine treatment , and then chromosomal specimen were
      prepared. The percentage of metaphase cells was examined under conditions above.
      Using this method, the variation rate of karyotype of YFF and CNF subcultured up
      to passage 20 were also analyzed. It was found that the percentage of YFF and CNF
      metaphase cells in treatment group were significantly higher than that in control
      group (p0.05), and the number of YFF and CNF metaphase cells obtained in 20 h
      treatment group were increased more than 6 fold as many as that in control group
      (p0.01), 31.7% and 40.2% vs 4.7% and 6.4% ,respectively. These data suggest that
      the method of freezing at 4 degrees could be used for increasing the number of
      metaphase cells in vitro conveniently, and analyzing the variation rate of
      karyotype of cultured cells efficiently.

PMID- 15985415
TI  - [Flow cytometric analysis and sorting of plant chromosomes.].
AB  - Flow cytometry refers to the technique where the measurement of the physical and
      chemical characteristics of particles including chromosomes, nuclei and cells is
      made as the particles pass in a fluid stream through a measuring point surrounded
      by an array of detectors. FCM (flow cytometry) analysis has played an important
      role in human genome projects. This technique is now increasingly used to
      establish flow karyotypes, sort chromosomes, map genes and construct DNA
      libraries in plants. This paper reviewed progress in flow cytometric analysis of
      plant genomes.

PMID- 15985416
TI  - [Progress of research on epigenetic and human disease.].
AB  - In the past few fears, there has been a nascent convergence of scientific
      understanding of human disease with epigenetic. Identified epigenetic processes
      involved in human disease include chromatin remodeling, genomic imprinting, X
      chromosome inactivation, and noncoding RNAs regulation. These processes influence
      chromatin structure and thereby regulate gene expression on the chromosome level
      or a cluster of linked genes level. Deregulation of these processes result in
      lots of disease which are characterized by complex patterns of mutations and
      associated phenotypes affecting pre- and postnatal growth, development, and
      neurological function. Epigenetic diseases are illustrated by the array of multi
      system disorders and neoplasias and investigations of these diseases have an
      impact on biomedical research and provide interesting models for functions and
      mechanisms of epigenetic gene control.

PMID- 15985417
TI  - [Mechanisms of epigenetic reprogramming in Mammalian resonstructed embryos
      produced by nuclear transfer.].
AB  - Circumstantial studies indicated that incomplete or inappropriate epigenetic
      reprogramming of donor nuclei was likely to be the primary reason for failures in
      nuclear transfer. In this view, we discussed the roles of several epigenetic
      mechanisms, including DNA methylation, chromatin remodeling, imprinting and X
      chromosome inactivation, telomere maintenance, and epigenetic inheritance in the
      observed abnormalities in clones from different species. Understanding the
      mechanisms underlying epigenetic reprogramming control will help us resolve the
      inherent problems in nuclear transfer technology and make its applications
      promising.

PMID- 15985418
TI  - [Growth differentiation factor 9 gene and its role in reproduction.].
AB  - Growth differentiation factor 9 (GDF9) secreted by oocyte is essential for
      follicular growth and differentiation. This review introduced the structure,
      function and regulation of GDF9, as well as the cloning and structure,
      developmental expression, mapping and polymorphism of GDF9 gene. The relationship
      between GDF9 gene and reproductive performance was also discussed in mammals.

PMID- 15985419
TI  - [Progress in the study on genetic mechanism for high prolificacy in farm
      animals.].
AB  - Reproduction ability of farm animals is a quantitative trait that affects largely
      the husbandry productions. Progress in the study on genetic mechanism for high
      prolificacy in farm animals were reviewed at genome level and mRNA expression
      level in this paper. All these research results indicate that high prolificacy is
      a trait affected by a lot of genes, that is, the co-expression and interaction of
      these genes result in the formation of the trait. A lot of progresses have been
      made at all these two research levels. But differing from the genome level, the
      research at mRNA expression level only involves the genes expressed at special
      time in special tissues, and the genes directly contributed to the formation of
      traits. The genetic mechanism for this trait has been studying at the levels of
      genome and mRNA expression nowadays. With the development of sciences, new
      research methods for the trait will be provided, but only the combination of them
      with all these research levels will be the most effective.

PMID- 15985420
TI  - [The research progress on molecular genetics of pathogenicity of rice blast
      fungus.].
AB  - Rice blast disease, caused by heterothallic ascomycete Magnaporthe grisea, is one
      of the most serious fungal diseases of rice throughout the world. The disease
      attacks rice plants throughout the season and causes severe yield losses. The
      pathogenesis of M. grisea is due to a complex process that spans the entire life
      cycle of the pathogen. The process including germination of conidia, formation of
      appressoria, differentiation of penetration pegs and proliferation of infectious
      hyphae is controlled by many genes. The interaction between M. grisea and rice is
      based on the gene-for-gene hypothesis and the defense responses are often
      activated by the action of the pathogen avirulence (Avr) gene and the host
      resistance (R) gene. The studies on molecular biology and genetic mechanism of
      pathogenicity of M. grisea has occupied pathologists and mycologists for several
      decades. This paper reviews the research progress related to molecular genetics
      of pathogenicity of the fungus and its genetic diversity and variation, and
      summarize research methods of the functional genes.

PMID- 15985421
TI  - [Advances in the Study on Marker Genes in transgenic Plants.].
AB  - Plant transgenic engineering is becoming more and more important in the world.
      The safety of selectable marker genes in the transgenic plants has been noticed
      widely. The new advances of selectable markers in transgenic plants were reviewed
      in this paper in three aspects. The first is the establishment of transformation
      systems allowing resistant marker genes to be eliminated from the transgenic
      plants, including co-transformation, site-specific recombination and
      transposition, as well as other methods. In these ways, the transgenes can be
      inserted into transgenic plants more than once. The second is the utilization and
      development of bio-safe positively selective marker genes, mainly referred to the
      carbohydrates metabolism genes, the stress- resistant enzymatic genes and the
      green fluorescent protein(GFP) gene. At the same time, the mercuric reductase
      genes, the key genes for chloroplast synthesis and other genes should also be
      quickly developed as markers. The third is the establishment of marker-free and
      skelecton-free transformation vector systems, which are efficient and simple. The
      prospects in application of these novel methods, marker free and safe selectable
      markers are also viewed in the article.

PMID- 15985422
TI  - [Advances in Detection Technologies of in vivo Expression of Bacterial Virulence
      Gene.].
AB  - The interactions between bacterial pathogens and their hosts is complex. To
      further our understanding ofathe pathogenesisaof bacterial pathogens, it is
      necessary to identify bacterial virulence genes that are specifically induced in
      vivo during infection and probe their regulation in vivo. Toward this end,
      several technologies, such as in vivo expression technology (IVET), signature
      tagged mutagenesis (STM), differential fluorescence induction (DFI), genomic
      analysis and mapping by in vitro transposition (GAMBIT) and in vivo induced
      antigen technology (IVIAT), have been developed. The purpose of this reviewais to
      update the reader on the many advances of these technologies, and to discuss
      their advantages and disadvantages.

PMID- 15985423
TI  - Modeling of an ion channel in its open conformation.
AB  - We have modeled the structure of KirBac1.1 in an open state using as a starting
      point the structure of KirBac1.1 in its closed conformation (Protein Data Bank
      1P7B). To test the validity of the open-state model, molecular dynamics
      simulations in octane, a lipid bilayer mimetic, were carried out. Simulations of
      the closed conformer were used for comparison purposes. The total simulation time
      was approximately 138 ns. The initial open model was refined by using projection
      maps obtained from electron microscopy experiments on two-dimensional crystals of
      the inwardly rectifying K+ channel KirBac3.1 from Magentospirillum
      magnetotacticum captured in its open state (C. Venien-Bryan, unpublished data).
      Significant movements of the outer helices take place in going from the closed to
      the open model in agreement with structural and biochemical data in potassium
      channels, which suggests that gating is accomplished by a conformational change
      that takes place in the transmembrane domain upon an external stimulus. The
      motion of the inner helices is mainly achieved by bending at conserved glycine
      residues that have been previously reported to act as molecular hinges. Overall,
      these simulations suggest that the open conformer is stable, providing a
      plausible all-atom model that will enable the study of potential gating
      mechanisms in more detail.

PMID- 15985424
TI  - The collapse of monolayers containing pulmonary surfactant phospholipids is
      kinetically determined.
AB  - Prior studies have shown that during and after slow compressions of monomolecular
      films containing the complete set of purified phospholipids (PPL) from calf
      surfactant at an air/water interface, surface pressures (pi) reach and sustain
      values that are remarkably high relative to expectations from simple systems with
      model lipids. Microscopy shows that the liquid-expanded, tilted-condensed, and
      collapsed phases are present together in the PPL films between 45 and 65 mN/m.
      The Gibbs phase rule restricts equilibrium coexistence of three phases to a
      single pi for films with two components but not for more constituents. We
      therefore determined if the surprising stability of PPL reflects release from the
      thermodynamic restrictions of simple model systems by the presence of multiple
      components. Experiments with binary films containing dioleoyl phosphatidylcholine
      and dipalmitoyl phosphatidylcholine first tested the predictions of the phase
      rule. The onset of three-phase coexistence, determined by fluorescence
      microscopy, and its termination, established by relaxation of collapsing films on
      a captive bubble, occurred at similar pi. Experiments for PPL using the same
      methods suggested that the three phases might coexist over a range of pi, but
      limited to approximately 2 mN/m, and extending below rather than above the
      coexistence pi for the binary films. Our results show that the PPL films at high
      pi must deviate from equilibrium and that they must then be metastable.

PMID- 15985425
TI  - Calcium ligation in photosystem II under inhibiting conditions.
AB  - In oxygenic photosynthesis, PSII carries out the oxidation of water and reduction
      of plastoquinone. The product of water oxidation is molecular oxygen. The water
      splitting complex is located on the lumenal side of the PSII reaction center and
      contains manganese, calcium, and chloride. Four sequential photooxidation
      reactions are required to generate oxygen from water; the five sequentially
      oxidized forms of the water splitting complex are known as the Sn states, where n
      refers to the number of oxidizing equivalents stored. Calcium plays a role in
      water oxidation; removal of calcium is associated with an inhibition of the S
      state cycle. Although calcium can be replaced by other cations in vitro, only
      strontium maintains activity, and the steady-state rate of oxygen evolution is
      decreased in strontium-reconstituted PSII. In this article, we study the role of
      calcium in PSII that is limited in water content. We report that strontium
      substitution or 18OH2 exchange causes conformational changes in the calcium
      ligation shell. The conformational change is detected because of a perturbation
      to calcium ligation during the S1 to S2 and S2 to S3 transition under water
      limited conditions.

PMID- 15985426
TI  - Superoxide radical formation by pure complex I (NADH:ubiquinone oxidoreductase)
      from Yarrowia lipolytica.
AB  - Generation of reactive oxygen species (ROS) is increasingly recognized as an
      important cellular process involved in numerous physiological and
      pathophysiological processes. Complex I (NADH:ubiquinone oxidoreductase) is
      considered as one of the major sources of ROS within mitochondria. Yet, the exact
      site and mechanism of superoxide production by this large membrane-bound
      multiprotein complex has remained controversial. Here we show that isolated
      complex I from Yarrowia lipolytica forms superoxide at a rate of 0.15% of the
      rate measured for catalytic turnover. Superoxide production is not inhibited by
      ubiquinone analogous inhibitors. Because mutant complex I lacking a detectable
      iron-sulfur cluster N2 exhibited the same rate of ROS production, this terminal
      redox center could be excluded as a source of electrons. From the effect of
      different ubiquinone derivatives and pH on this side reaction of complex I we
      concluded that oxygen accepts electrons from FMNH2 or FMN semiquinone either
      directly or via more hydrophilic ubiquinone derivatives.

PMID- 15985427
TI  - Thioredoxin reductase system mediates iron binding in IscA and iron delivery for
      the iron-sulfur cluster assembly in IscU.
AB  - IscA is a key member of the iron-sulfur cluster assembly machinery found in
      bacteria and eukaryotes. Previously, IscA was characterized as an alternative
      iron-sulfur cluster assembly scaffold, as purified IscA can host transient iron
      sulfur clusters. However, recent studies indicated that IscA is an iron-binding
      protein that can provide iron for the iron-sulfur cluster assembly in a proposed
      scaffold IscU (Ding H., Clark, R. J., and Ding, B. (2004) J. Biol. Chem. 279,
      37499-37504). To further elucidate the roles of IscA in the biogenesis of iron
      sulfur clusters, we reevaluate the iron binding activity of IscA under
      physiologically relevant conditions. The results indicate that in the presence of
      the thioredoxin reductase system, Escherichia coli IscA binds iron with an iron
      association constant of 2.0 x 10(19) M(-1) in vitro. Whereas all three components
      (thioredoxin 1, thioredoxin reductase and NADPH) in the thioredoxin reductase
      system are essential for mediating the iron binding in IscA, only catalytic
      amounts of thioredoxin 1 and thioredoxin reductase are required. In contrast,
      IscU fails to bind iron in the presence of the thioredoxin reductase system,
      suggesting that the iron binding in IscA is specific. Nevertheless, the
      thioredoxin reductase system can promote the iron-sulfur cluster assembly in IscU
      in the presence of the iron-loaded IscA, cysteine desulfurase (IscS), and L
      cysteine, demonstrating a physiologically relevant system for the biogenesis of
      iron-sulfur clusters. The results provide additional evidence for the hypothesis
      that IscA is capable of recruiting intracellular "free" iron and delivering the
      iron for the iron-sulfur cluster assembly in IscU.

PMID- 15985428
TI  - H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through
      positive control by E2F1.
AB  - The imprinted H19 gene has riboregulatory functions. We show here that H19
      transcription is up-regulated during the S-phase of growth-stimulated cells and
      that the H19 promoter is activated by E2F1 in breast cancer cells. H19 repression
      by pRb and E2F6 confirms the E2F1-dependent control of the H19 promoter.
      Consistently, we demonstrate by chromatin immunoprecipitation assays that
      endogenous E2F1 is recruited to the H19 promoter in vivo. The functionality of
      E2F promoter sites was further confirmed by gel shift and mutagenesis
      experiments, revealing that these sites are required for binding and promoter
      response to E2F1 exogenous expression and serum stimulation. Furthermore, we show
      that H19 overexpression confers a growth advantage on breast cancer cells
      released from growth arrest as well as in asynchronously growing cells. The H19
      knockdown by small interfering RNA duplexes impedes S-phase entry in both wild
      type and stably H19-transfected cells. Based on these findings, we conclude that
      the H19 RNA is actively linked to E2F1 to promote cell cycle progression of
      breast cancer cells. This clearly supports the H19 oncogenic function in breast
      tumor genesis.

PMID- 15985429
TI  - Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2
      activation.
AB  - Activation of the transcription factor Nrf2 regulates expression of phase II
      enzymes and other adaptive responses to electrophile and oxidant stress. Nrf2
      concentrations are regulated by the thiol-rich sensor protein Keap1, which is an
      adaptor protein for Cul3-dependent ubiquitination and degradation of Nrf2.
      However, the links between site specificity of Keap1 modification by
      electrophiles and mechanisms of Nrf2 activation are poorly understood. We studied
      the actions of the prototypical Nrf2 inducer tert-butylhydroquinone (tBHQ) and
      two biotin-tagged, thiol-reactive electrophiles, N-iodoacetyl-N
      biotinylhexylenediamine (IAB) and 1-biotinamido-4-(4'-[maleimidoethyl
      cyclohexane]-carboxamido)butane (BMCC). Both IAB and tBHQ induced antioxidant
      response element (ARE)-directed green fluorescent protein (GFP) expression in
      ARE/thymidine kinase GFP HepG2 cells, and both initiated nuclear Nrf2
      accumulation and induction of heme oxygenase 1 in HEK293 cells. In contrast, BMCC
      produced none of these effects. Liquid chromatography tandem mass spectrometry
      (MS-MS) analysis of human Keap1 modified by IAB or BMCC in vitro indicated that
      IAB adduction occurred primarily in the central linker domain, whereas BMCC
      modified other Keap1 domains. Treatment of FLAG-Keap1-transfected HEK293 with the
      Nrf2-activating compounds IAB and tBHQ generated high molecular weight Keap1
      forms, which were identified as K-48-linked polyubiquitin conjugates by
      immunoblotting and liquid chromatography MS-MS. Keap1 polyubiquitination
      coincided with Nrf2 stabilization and nuclear accumulation. In contrast, BMCC did
      not induce Keap1 polyubiquitination. Our results suggest that Nrf2 activation is
      regulated through the polyubiquitination of Keap1, which in turn is triggered by
      specific patterns of electrophile modification of the Keap1 central linker
      domain. These results suggest that Keap1 adduction triggers a switching of Cul3
      dependent ubiquitination from Nrf2 to Keap1, leading to Nrf2 activation.

PMID- 15985430
TI  - Involvement of inflammation, degradation, and apoptosis in a mouse model of
      glaucoma.
AB  - Glaucoma is a common cause of blindness affecting at least 66 million people
      worldwide. Pigmentary glaucoma is one of the most common forms of secondary
      glaucoma, and its pathogenesis remains unclear. Interleukin-18 (IL-18) is an
      important regulator of innate and acquired immune responses and plays an
      important role in inflammatory/autoimmunity diseases. Using the DBA/2J mouse as
      an animal model of human pigmentary glaucoma, we demonstrated for the first time
      that the expression of the IL-18 protein and gene in the iris/ciliary body and
      level of IL-18 protein in the aqueous humor of DBA/2J mice are dramatically
      increased with age. This increase precedes the onset of clinical evidence of
      pigmentary glaucoma, implying a pathogenic role of inflammation/immunity in this
      disease. We also observed that activated NF-kappaB and phosphorylated MAPK are
      increased in the iris/ciliary body of DBA/2J mice, suggesting that both signaling
      pathways may be involved in IL-18 mediated pathogenesis of pigmentary glaucoma in
      the eyes of DBA/2J mice. In addition, matrix metalloproteinase-2 (MMP-2)
      expression in the iris/ciliary body and the activity of MMP-2 in the aqueous
      humor are increased whereas tissue inhibitor of matrix metalloproteinase-1 (TIMP
      1) expression in the iris/ciliary body is decreased, indicating that the
      degradation process is involved in this mouse model of pigmentary glaucoma.
      Furthermore, the expressions of apoptosis-related genes, caspase-8, Fas, FADD,
      FAP, and FAF, and the activity of caspase-3 are increased in the iris/ciliary
      body of DBA/2J mice. Elucidation of biochemical and molecular mechanisms of IL-18
      participation in the pathogenesis of pigmentary glaucoma should provide
      approaches for developing improved and targeted treatments to ameliorate this
      blinding disease. The possibility that altered IL-18 expression in the eye of
      DBA/2J mice initiates and/or amplifies the pathogenesis of pigmentary glaucoma
      requires further investigation.

PMID- 15985431
TI  - Tumor cell pseudopodial protrusions. Localized signaling domains coordinating
      cytoskeleton remodeling, cell adhesion, glycolysis, RNA translocation, and
      protein translation.
AB  - The pseudopodial protrusions of Moloney sarcoma virus (MSV)-Madin-Darby canine
      kidney (MDCK)-invasive (INV) variant cells were purified on 1-microm pore
      polycarbonate filters that selectively allow passage of the pseudopodial domains
      but not the cell body. The purified pseudopodial fraction contains
      phosphotyrosinated proteins, including Met and FAK, and various signaling
      proteins, including Raf1, MEK1, ERK2, PKBalpha (Akt1), GSK3alpha, GSK3beta, Rb,
      and Stat3. Pseudopodial proteins identified by liquid chromatography tandem mass
      spectrometry included actin and actin-regulatory proteins (ERM, calpain, filamin,
      myosin, Sra-1, and IQGAP1), tubulin, vimentin, adhesion proteins (vinculin,
      talin, and beta1 integrin), glycolytic enzymes, proteins associated with protein
      translation, RNA translocation, and ubiquitin-mediated protein degradation, as
      well as protein chaperones (HSP90 and HSC70) and signaling proteins (RhoGDI and
      ROCK). Inhibitors of MEK1 (U0126) and HSP90 (geldanamycin) significantly reduced
      MSV-MDCK-INV cell motility and pseudopod expression, and geldanamycin treatment
      inhibited Met phosphorylation and induced the expression of actin stress fibers.
      ROCK inhibition did not inhibit cell motility but transformed the pseudopodial
      protrusions of MSV-MDCK-INV cells into extended lamellipodia. Dominant negative
      Rho disrupted pseudopod expression and, in serum-starved cells, L-alpha
      lysophosphatidic acid (oleoyl) activation of Rho induced pseudopodial protrusions
      or, in the presence of the ROCK inhibitor, extended lamellipodia. RNA was
      localized to the actin-rich pseudopodial domains of MSV-MDCK-INV cells, but the
      extent of colocalization with dense actin ruffles was reduced in the extended
      lamellipodia formed upon ROCK inhibition. Rho/ROCK activation in epithelial tumor
      cells therefore regulates RNA translocation to a pseudopodial domain that
      contains proteins involved in signaling, cytoskeleton remodeling, cell adhesion,
      glycolysis, and protein translation and degradation.

PMID- 15985432
TI  - Flow activates ERK1/2 and endothelial nitric oxide synthase via a pathway
      involving PECAM1, SHP2, and Tie2.
AB  - Blood flow modulates endothelial cell (EC) functions through specific signaling
      events. Previous data show that flow stimulates SHP2 translocation to cell
      membranes and binding to phosphotyrosine proteins. Flow-induced ERK1/2
      phosphorylation depends on SHP2 phosphatase activity and SHP2 binding to phospho
      PECAM1 (platelet endothelial adhesion molecule 1), suggesting that SHP2 forms a
      signaling module with PECAM1. We hypothesized that flow induces assembly of the
      multi-protein complexes with SHP2 that are required for downstream signaling. ECs
      were exposed to flow for 10 min, and endogenous SHP2 was immunoprecipitated. SHP2
      associated proteins were analyzed by SDS-PAGE and identified by mass
      spectrometry. Tie2 and several known SHP2-binding proteins were identified in
      flow-induced SHP2 complexes. Flow significantly increased tyrosine
      phosphorylation of both Tie2 and PECAM1 and their association with SHP2. To
      evaluate their functional roles, ECs were treated with Tie2 or PECAM1 small
      interfering RNA (siRNA). Tie2 and PECAM1 expression decreased >80% after siRNA
      treatment, and flow-stimulated phosphorylation of ERK1/2, Akt, and endothelial
      nitric oxide synthase was significantly inhibited by Tie2 and PECAM1 siRNA. Tie2
      phosphorylation by flow was significantly inhibited by PECAM1 siRNA treatment.
      These results establish Tie2 transactivation via PECAM1 as an early event in flow
      mediated mechanotransduction and suggest an important role for a PECAM1-SHP2-Tie2
      pathway in flow-mediated signal transduction.

PMID- 15985433
TI  - Loss of the von Hippel Lindau tumor suppressor disrupts iron homeostasis in renal
      carcinoma cells.
AB  - Given the modulation of iron metabolism by hypoxia and the high iron requirement
      of neoplastic cells, we investigated iron metabolism in a human renal cancer cell
      line with a mutated von Hippel Lindau (VHL) tumor suppressor gene (RCC10) and in
      a transfectant clone with wild-type VHL (RCC63). The loss of VHL strongly up
      regulated transferrin receptor expression in RCC10 cells as a result of hypoxia
      inducible factor-1 (HIF-1)-mediated transcriptional activation, leading to an
      increased uptake of transferrin-bound 55Fe. Increased iron availability did not
      compromise the resistance of VHL-defective cells to oxidative stress or promote
      faster cell multiplication. Surprisingly, the content of ferritin H and L
      subunits and ferritin mRNA levels were considerably lower in the RCC10 than in
      the RCC63 cells. Despite the similarities between HIF-1 and iron regulatory
      protein 2 (IRP2), we found no evidence of specific regulation of IRP2 by VHL.
      However, both IRP2 and IRP1 were slightly activated in RCC10 cells, thus
      indicating that this cell line has a somewhat reduced labile iron pool (LIP). The
      finding that RCC10 cells had a lower ferritin content but more ferritin
      associated 55Fe than RCC63 explains why VHL-lacking cells may have a smaller LIP
      despite increased iron uptake. We also found a correlation between cytoprotection
      from iron-mediated damage and efficient incorporation into ferritin of both
      transferrin and non-transferrin-bound 55Fe. This study shows that, like oncogene
      activation, the loss of an oncosuppressor rearranges the expression pattern of
      the genes of iron metabolism to increase iron availability. However, in the case
      of VHL loss, mechanisms affecting iron handling by ferritin somehow counteract
      the effects that the reduced content of this protective protein may have on
      proliferation and oxidant sensitivity.

PMID- 15985434
TI  - Crystal structure of pyridoxal kinase in complex with roscovitine and
      derivatives.
AB  - Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine,
      and pyridoxine in the presence of ATP and Zn2+. This constitutes an essential
      step in the synthesis of pyridoxal 5'-phosphate (PLP), the active form of vitamin
      B6, a cofactor for over 140 enzymes. (R)-Roscovitine (CYC202, Seliciclib) is a
      relatively selective inhibitor of cyclin-dependent kinases (CDKs), currently
      evaluated for the treatment of cancers, neurodegenerative disorders, renal
      diseases, and several viral infections. Affinity chromatography investigations
      have shown that (R)-roscovitine also interacts with PDXK. To understand this
      interaction, we determined the crystal structure of PDXK in complex with (R)
      roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter
      derivatives being designed to bind to PDXK but not to CDKs. Structural analysis
      revealed that these three roscovitines bind similarly in the pyridoxal-binding
      site of PDXK rather than in the anticipated ATP-binding site. The pyridoxal
      pocket has thus an unexpected ability to accommodate molecules different from and
      larger than pyridoxal. This work provides detailed structural information on the
      interactions between PDXK and roscovitine and analogs. It could also aid in the
      design of roscovitine derivatives displaying strict selectivity for either PDXK
      or CDKs.

PMID- 15985435
TI  - Protein import, replication, and inheritance of a vestigial mitochondrion.
AB  - Mitochondrial remnant organelles (mitosomes) that exist in a range of
      "amitochondrial" eukaryotic organisms represent ideal models for the study of
      mitochondrial evolution and for the establishment of the minimal set of proteins
      required for the biogenesis of an endosymbiosis-derived organelle. Giardia
      intestinalis, often described as the earliest branching eukaryote, contains
      double membrane-bounded structures involved in iron-sulfur cluster biosynthesis,
      an essential function of mitochondria. Here we present evidence that Giardia
      mitosomes also harbor Cpn60, mtHsp70, and ferredoxin and that despite their
      advanced state of reductive evolution they have retained vestiges of presequence
      dependent and -independent protein import pathways akin to those that operate in
      mammalian mitochondria. Although import of IscU and ferredoxin is still reliant
      on their amino-terminal presequences, targeting of Giardia Cpn60, IscS, or
      mtHsp70 into mitosomes no longer requires cleavable presequences, a derived
      feature from their mitochondrial homologues. In addition, we found that division
      and segregation of a single centrally positioned mitosome tightly associated with
      the microtubular cytoskeleton is coordinated with the cell cycle, whereas
      peripherally located mitosomes are inherited into daughter cells stochastically.

PMID- 15985436
TI  - A role of p73 in mitotic exit.
AB  - The p53-related p73 proteins regulate developmental processes, cell growth, and
      DNA damage response. p73 function is regulated by post-translational
      modifications and protein-protein interactions. At the G2/M transition, p73 is
      phosphorylated at Thr-86 by the p34cdc2/cyclin B complex; this is associated with
      its exclusion from condensed chromosomes and loss of DNA binding and
      transcriptional activation ability. Here we showed that p73 hypo-phosphorylated
      species reappear during mitotic exit, concomitant with p73 relocalization to
      telophase nuclei and recovered ability to activate transcription. Functional
      knock-out of p73 gene expression by small interfering RNAs (siRNAs) alters
      mitotic progression, yielding an increase of ana-telophase cells, the
      accumulation of aberrant late mitotic figures, and the appearance of
      abnormalities in the subsequent interphase. This p73 activity at the M-to-G1
      transition is mediated by its transactivating function because expression of the
      transcription dominant negative mutant p73DD induces the same mitotic exit
      phenotype. We also found that the cyclin-dependent kinase inhibitor Kip2/p57 gene
      is a specific target of p73 regulation during mitotic exit and re-entry into G1.
      Both knock-out of p73 gene expression by siRNAs and abrogation of p73-dependent
      transcription by the p73DD mutant abrogate Kip2/p57 increase at the M-to-G1
      transition. Moreover, similar abnormalities (e.g. delay in late mitotic stages
      with the accumulation of aberrant ana-telophase figures, and abnormalities in the
      following interphase) are observed in cultures in which the expression of
      Kip2/p57 is abrogated by siRNAs. These results identify a novel p73-Kip2/p57
      pathway that coordinates mitotic exit and transition to G1.

PMID- 15985437
TI  - Protofibril formation of amyloid beta-protein at low pH via a non-cooperative
      elongation mechanism.
AB  - Deposition of the amyloid beta-protein (Abeta) in senile or diffuse plaques is a
      distinctive feature of Alzheimer's disease. The role of Abeta aggregates in the
      etiology of the disease is still controversial. The formation of linear
      aggregates, known as amyloid fibrils, has been proposed as the onset and the
      cause of pathological deposition. Yet, recent findings suggest that a more
      crucial role is played by prefibrillar oligomeric assemblies of Abeta that are
      highly toxic in the extracellular environment. In the present work, the mechanism
      of protofibril formation is studied at pH 3.1, starting from a solution of
      oligomeric precursors. By combining static light scattering and photon
      correlation spectroscopy, the growth of the mass and the size of aggregates are
      determined at different temperatures. Analysis and scaling of kinetic data reveal
      that under the studied conditions protofibrils are formed via a single non
      cooperative elongation mechanism, not prompted by nucleation. This process is
      well described as a linear colloidal aggregation due to diffusion and coalescence
      of growing aggregates. The rate of elongation follows an Arrhenius law with an
      activation enthalpy of 15 kcal mol(-1). Such a value points to a conformational
      change of peptides or oligomers being involved in binding to protofibrils or in
      general to a local reorganization of each aggregate. These results contribute to
      establishing a clearer relation at the molecular level between the fibrillation
      mechanism and fibrillar precursors. The observation of a non-cooperative
      aggregation pathway supports the hypothesis that amyloid formation may represent
      an escape route from a dangerous condition, induced by the presence of toxic
      oligomeric species.

PMID- 15985438
TI  - Secretase-dependent tyrosine phosphorylation of Mdm2 by the ErbB-4 intracellular
      domain fragment.
AB  - Heregulin activation of the endogenous receptor tyrosine kinase ErbB-4 in ZR-75-1
      breast cancer cells provokes tyrosine phosphorylation of Hdm2 in a manner that is
      sensitive to inhibition of alpha- or gamma-secretase activity, indicating that
      liberation of the tyrosine kinase intracellular domain (ICD) fragment is
      required. Similar results are obtained when Erbb-4 is exogenously expressed in
      32D cells, which do not otherwise express any ErbB family members. Expression of
      the ErbB-4 ICD fragment leads to its constitutive association with Mdm2 and
      tyrosine phosphorylation of Mdm2, a protein that is predominantly localized in
      the nucleus and that regulates p53 levels. When the ErbB-4 ICD fragment was
      expressed in H1299 cells, it promoted Hdm2 ubiquitination and increased the
      levels of p53 and p21, a transcriptional target of p53. In addition, expression
      of the ICD fragment increased p53 activity toward the p21 promoter in a
      luciferase reporter assay.

PMID- 15985439
TI  - Investigating the receptor-independent neuroprotective mechanisms of nicotine in
      mitochondria.
AB  - Although nicotine has been associated with a decreased risk of developing
      Parkinson disease, the underlying mechanisms are still unclear. By using isolated
      brain mitochondria, we found that nicotine inhibited N-methyl-4-phenylpyridine
      (MPP(+)) and calcium-induced mitochondria high amplitude swelling and cytochrome
      c release from intact mitochondria. Intra-mitochondria redox state was also
      maintained by nicotine, which could be attributed to an attenuation of
      mitochondria permeability transition. Further investigation revealed that
      nicotine did not prevent MPP(+)- or calcium-induced mitochondria membrane
      potential loss, but instead decreased the electron leak at the site of
      respiratory chain complex I. In the presence of mecamylamine hydrochloride, a
      nonselective nicotinic acetylcholine receptor inhibitor, nicotine significantly
      postponed mitochondria swelling and cytochrome c release induced by a mixture of
      neurotoxins (MPP(+) and 6-hydroxydopamine) in SH-SY5Y cells, suggesting that
      there is a receptor-independent nicotine-mediated neuroprotective effect of
      nicotine. These results show that interaction of nicotine with mitochondria
      respiratory chain together with its antioxidant effects should be considered in
      the neuroprotective effects of nicotine.

PMID- 15985440
TI  - Selective chromosome analysis in couples with two or more miscarriages: case
      control study.
AB  - OBJECTIVE: To identify additional factors, such as maternal age or factors
      related to previous reproductive outcome or family history, and the corresponding
      probability of carrying a chromosome abnormality in couples with two or more
      miscarriages. DESIGN: Nested case-control study. SETTING: Six centres for
      clinical genetics in the Netherlands. PARTICIPANTS: Couples referred for
      chromosome analysis after two or more miscarriages in 1992-2000; 279 carrier
      couples were marked as cases, and 428 non-carrier couples served as controls.
      MAIN OUTCOME MEASURES: Independent factors influencing the probability of carrier
      status and the corresponding probability of carrier status. RESULTS: Four factors
      influencing the probability of carrier status could be identified: maternal age
      at second miscarriage, a history of three or more miscarriages, a history of two
      or more miscarriages in a brother or sister of either partner, and a history of
      two or more miscarriages in the parents of either partner. The calculated
      probability of carrier status in couples referred for chromosome analysis after
      two or more miscarriages varied between 0.5% and 10.2%. CONCLUSIONS: The
      probability of carrier status in couples with two or more miscarriages is
      modified by additional factors. Selective chromosome analysis would result in a
      more appropriate referral policy, could decrease the annual number of chromosome
      analyses, and could therefore lower the costs.

PMID- 15985441
TI  - The death rate among hospitalized heart failure patients with normal and
      depressed left ventricular ejection fraction in the year following discharge:
      evolution over a 10-year period.
AB  - AIMS: To investigate whether changes in clinical characteristics and treatment
      strategies between 1991 and 2001 have had an impact on the survival of patients
      hospitalized with congestive heart failure (CHF) and whether those with normal
      left ventricular ejection fraction (LVEF> or =50%) differ in this respect from
      those with depressed LVEF. METHODS AND RESULTS: We studied 1482 patients who had
      been admitted to the Cardiology Service of a tertiary Spanish hospital in the
      last 10 years with CHF. Among the 1110 for whom LVEF was evaluated, the
      prevalence of normal LVEF rose from 37% in the period 1991-96 (Period 1) to 47%
      in the period 2000-2001 (Period 3). The intensity of both diagnostic and
      therapeutic measures also increased during this 10-year period. The 1-year
      survival rate remained virtually unchanged in the whole group of patients, being
      82, 84, and 82% in Periods 1, 2 (1997-99), and 3, respectively, even though the
      prognosis of patients with depressed LVEF (<50%) improved significantly, with 1
      year survival rates of 76, 77, and 84% in Periods 1, 2, and 3, respectively; the
      normal LVEF group had decreasing 1-year survival rates of 88, 86, and 81% in
      Periods 1, 2, and 3, respectively, although the increased risk of death was not
      statistically significant. CONCLUSION: Although in our centre the death rate
      among hospitalized CHF patients with depressed LVEF during the first year after
      discharge has tended to fall over the past 10 years, application of current
      clinical guidelines has led to no such decrease for patients with normal LVEF.
      This situation points to a need to reconsider the diagnostic and therapeutic
      strategy to be employed with this latter group of patients.

PMID- 15985442
TI  - Genetic modification and variations in solvent increase the sensitivity of the
      yeast RAD54-GFP genotoxicity assay.
AB  - The yeast (Saccharomyces cerevisiae) RAD54-GFP DNA repair reporter assay
      (GreenScreen assay, GSA) can be used for early genotoxicity screening in drug
      discovery. During the initial validation of this preregulatory assay, a subset of
      known genotoxic compounds that did not give reproducibly clear positive GSA
      results was identified. Cell permeability, inherent drug resistance mechanisms,
      metabolic activation and compound solubility were identified as possible barriers
      to the detection of specific compounds. In this study three types of modification
      to the existing assay protocol were explored in order to address these
      possibilities: (i) modification of the reporter host strain by deletion of genes
      involved in cell wall integrity or with products functioning as efflux pumps
      (PDR5, ERG6, SNQ2, YOR1); (ii) expression in the host yeast of human phase I
      metabolic activation genes and (iii) variation in the test solvent system for
      compounds with poor aqueous solubility. The modifications described and the assay
      results presented show how the assay may be tailored to suit specific classes of
      test compound in a more analytical mode. Improvements in assay sensitivity were
      seen in the detection of some genotoxins using yeast cell wall mutants and those
      expressing human cytochrome P450 genes.

PMID- 15985443
TI  - Lipoperoxidation products and thiol antioxidants in chromium exposed workers.
AB  - Hexavalent chromium is an established carcinogenic agent, which is not directly
      reactive with DNA. Its genotoxicity involves a reduction step, producing reactive
      oxygen species and radicals, and also lower valence forms which form stable
      complexes with intracellular macromolecules. The trivalent form of chromium may
      directly react with the genetic material and has also been shown to generate
      oxidative damage in vitro. To further evaluate the importance of in vivo
      oxidative DNA damage in the toxicity of each valence form, we conducted a
      comparative study on hexavalent and trivalent chromium-exposed workers (manual
      metal arc stainless steel welders and leather tanning workers), focusing on the
      total oxidative status by quantifying the level of lipoperoxidation products in
      urine. Thiol antioxidants are important in response to oxidative stress, and
      therefore, the concentration of glutathione and cysteine in peripheral blood
      lymphocytes was also determined. Chromium exposure was evaluated by quantifying
      total chromium in plasma and urine. Both groups had a significant increase in
      lipid peroxidation products expressed as malondialdehyde (MDA) in urine (tanners
      1.42 +/- 0.61 micromol/g creatinine, welders 1.67 +/- 1.13 micromol/g creatinine
      versus controls 0.81 +/- 0.26 micromol/g creatinine, P < 0.005 in both cases) but
      only welders had a significant decrease in glutathione concentration in
      lymphocytes. There was a positive correlation between chromium in plasma and
      urinary MDA in welders, but not in tanners. This work is part of a larger study
      of which major results have been published previously including cytogenetics and
      DNA-protein cross-links in workers exposed to the two different forms of
      chromium. These results are compared with the results of oxidative damage from
      this study.

PMID- 15985446
TI  - Health promotion--quo vadis now?

PMID- 15985444
TI  - Concerning: Prevalence and awareness of risk factors and behaviours of coronary
      heart disease in an urban population of Karachi.

PMID- 15985447
TI  - Unsung heroes who put their lives at risk? Informal caring, health and
      neighbourhood attachment.
AB  - BACKGROUND: Previous studies have highlighted the effects of informal caring on
      mental health, but evidence for its wider impact remains scant. We explored
      associations between informal care and a range of health (and health-related)
      measures. We also considered previously neglected differences between informal
      care 'at home' and care elsewhere, along with neighbourhood attachment as a
      possible modifier of the associations we found. METHODS: The study involved a
      large population survey in two Primary Care Trusts. Data were collected by postal
      survey of 15,465 adults; subjects were selected from the local General Practice
      register. 12.7 per cent of respondents identified themselves as carers. Health
      measures included psychiatric morbidity, bodily pain, self-assessed health,
      health-related behaviours, obesity, prescribed drugs and high levels of GP
      consultation. RESULTS: Of nine measures considered, care at home was associated
      with psychiatric morbidity (OR 1.46, 95 per cent CI 1.25--1.70), bodily pain (OR
      1.19, 95 per cent CI 1.02--1.39), and obesity (OR 1.59, 95 per cent CI 1.34-
      1.89). Care 'away' was associated with smoking (OR 1.26, 95 per cent CI 1.03-
      1.54), and inversely with both sedentary living (OR 0.70, 95 per cent CI 0.58-
      0.85) and poor self-assessed health (OR 0.78, 95 per cent CI 0.62--0.99). Health
      tended to be poorer when carers lacked a sense of neighbourhood attachment.
      CONCLUSIONS: Informal carers are likely to face serious health challenges besides
      anxiety and depression. Caring is associated with several aspects of poor health,
      which are themselves predictors of premature mortality. Proactive and wide
      ranging support is required, the more so in neighbourhoods where carers feel
      alienated. Research and policy should distinguish carers 'at home' from carers
      'away'.

PMID- 15985448
TI  - Observed and expected prevalence of permanent childhood hearing impairment in
      Oldham.
AB  - BACKGROUND: A perceived high prevalence of permanent childhood hearing impairment
      in Oldham, particularly in the Asian community, caused concern during the local
      implementation of the Newborn Hearing Screening Programme. METHODS: A
      retrospective cohort study of cases with dates of birth between 1 January 1986
      and 31 May 2003 was undertaken to describe local epidemiology and establish the
      observed prevalence rate. Expected prevalence was determined by application of
      published national rates to the susceptible Oldham population. RESULTS: The study
      identified 132 children in Oldham meeting the case definition. The prevalence of
      permanent childhood hearing impairment in the non-Asian community (1.34/1,000
      live births) was equal to published national rates (1.33/1,000 live births), but
      that in the Asian community (4.64/1,000 live births) indicated a relative risk of
      3.5. Differences in prevalence between observed and expected rates was greater
      than would have occurred by chance (p<0.001). CONCLUSION: The clinical suspicion
      of a raised local prevalence of permanent childhood hearing impairment in Oldham
      was confirmed. The importance of using locally derived data when implementing
      national policy is emphasized.

PMID- 15985449
TI  - The social impact of land contamination: reflections on the development of a
      community advocacy and counselling service following the Weston village incident.
AB  - Five years ago the village of Weston in Cheshire was affected by one of Britain's
      largest community-based land contamination incidents. The need for some form of
      community-based service incorporating social support and advocacy was identified
      and North Cheshire Health Authority in collaboration with the local community
      trust developed an advocacy and counselling service within the village. This
      article presents reflections on this highly complex service by reviewing the
      Weston incident, its management and possible lessons for public health
      practitioners dealing with similar incidents.

PMID- 15985450
TI  - Adenine nucleotide regulation in pancreatic beta-cells: modeling of ATP/ADP-Ca2+
      interactions.
AB  - Glucose metabolism stimulates insulin secretion in pancreatic beta-cells. A
      consequence of metabolism is an increase in the ratio of ATP to ADP ([ATP]/[ADP])
      that contributes to depolarization of the plasma membrane via inhibition of ATP
      sensitive K+ (K(ATP)) channels. The subsequent activation of calcium channels and
      increased intracellular calcium leads to insulin exocytosis. Here we evaluate new
      data and review the literature on nucleotide pool regulation to determine the
      utility and predictive value of a new mathematical model of ion and metabolic
      flux regulation in beta-cells. The model relates glucose consumption, nucleotide
      pool concentration, respiration, Ca2+ flux, and K(ATP) channel activity. The
      results support the hypothesis that beta-cells maintain a relatively high
      [ATP]/[ADP] value even in low glucose and that dramatically decreased free ADP
      with only modestly increased ATP follows from glucose metabolism. We suggest that
      the mechanism in beta-cells that leads to this result can simply involve keeping
      the total adenine nucleotide concentration unchanged during a glucose elevation
      if a high [ATP]/[ADP] ratio exits even at low glucose levels. Furthermore,
      modeling shows that independent glucose-induced oscillations of intracellular
      calcium can lead to slow oscillations in nucleotide concentrations, further
      predicting an influence of calcium flux on other metabolic oscillations. The
      results demonstrate the utility of comprehensive mathematical modeling in
      understanding the ramifications of potential defects in beta-cell function in
      diabetes.

PMID- 15985451
TI  - Leukemia inhibitory factor regulates glucocorticoid receptor expression in the
      hypothalamic-pituitary-adrenal axis.
AB  - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130
      family. LIF is induced peripherally and within the brain during inflammatory or
      chronic autoimmune diseases and is a potent stimulator of the hypothalamic
      pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating
      glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3
      microg/mouse, i.p.) markedly decreased GR mRNA levels in murine hypothalamus (5
      fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein
      levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within
      2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA
      reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants
      of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF
      effects on GR expression. Conversely, mice with LIF deficiency exhibited
      increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold,
      respectively; P < 0.01 for both) and increased GR protein expression when
      compared with wild-type littermates. The suppressive effects of dexamethasone on
      GR were more pronounced in LIF-null animals. These data suggest that LIF
      maintains the HPA axis activation by decreasing GR expression and raise the
      possibility that LIF might contribute to the development of central
      glucocorticoid resistance during inflammation.

PMID- 15985452
TI  - Insulin secretion by rat lacrimal glands: effects of systemic and local
      variables.
AB  - To understand the secretory mechanisms and physiological role of insulin in the
      tear film, the present study examined 1) the time course of insulin secretion in
      the tear film under glucose intravenous stimulation, 2) the glucose- and
      carbachol-induced insulin secretion from isolated lacrimal gland (LG), 3) the
      effect of insulin on glucose consumption by the cornea, and 4) the expression of
      insulin, pancreatic duodenal homeobox-1 (PDX-1), and glucose transport proteins
      (GLUTs) in LG tissue. The insulin level in the tear film of 8-wk-old male Wistar
      rats increased from 0.6 +/- 0.45 to 3.7 +/- 1.3 ng/ml in the initial minutes
      after glucose stimulation. In vitro assays demonstrated that higher glucose
      concentrations from 2.8 to 16.7 mM, 200 microM carbachol, or 40 mM KCl
      significantly increased insulin secretion from lacrimal glands compared with
      controls, but did not detect C-peptide as measured by RIA. Glucose consumption by
      corneal tissue, evaluated by radiolabeled D-[U-14C]glucose uptake, was 24.07 +/-
      0.61 and was enhanced to 31.63 +/- 3.15 nmol x cornea(-1) x 2 h(-1) in the
      presence of 6 nM insulin (P = 0.033) and to 37.5 +/- 3.7 nmol x cornea(-1) x 2 h(
      1) in the presence of 11.2 mM glucose (P = 0.015). Insulin and PDX-1 mRNA was
      detected in LG. Insulin was located in the apical areas of acinar cells by
      immunoperoxidase and the expression of GLUT-1, but not PDX-1, was confirmed by
      Western blot. These findings suggest that insulin secretion in the tear film is
      influenced by local stimuli such as nutrient and neural inputs and that this
      hormone plays a metabolic role in ocular surface tissues. These data also
      indicate that under normal conditions the insulin secreted by LG is stored, but
      it is not clear that is locally produced in the LG.

PMID- 15985453
TI  - Effects of long-term treatment with growth hormone-releasing peptide-2 in the
      GHRH knockout mouse.
AB  - Growth hormone (GH) secretagogues (GHS) stimulate GH secretion in vivo in humans
      and in animals. They act on the ghrelin receptor, expressed in both the
      hypothalamus and the pituitary. It is unknown whether GHSs act predominantly by
      increasing the release of hypothalamic GH-releasing hormone (GHRH) or by acting
      directly on the somatotroph cells. We studied whether a potent GHS could
      stimulate growth in the absence of endogenous GHRH. To this end, we used GHRH
      knockout (GHRH-KO) mice. These animals have proportionate dwarfism due to severe
      GH deficiency (GHD) and pituitary hypoplasia due to reduced somatotroph cell
      mass. We treated male GHRH-KO mice for 6 wk (from week 1 to week 7 of age) with
      GH-releasing peptide-2 (GHRP-2, 10 microg s.c. twice a day). Chronic treatment
      with GHRP-2 failed to stimulate somatotroph cell proliferation and GH secretion
      and to promote longitudinal growth. GHRP-2-treated mice showed an increase in
      total body weight compared with placebo-treated animals, due to worsening of the
      body composition alterations typical of GHD animals. These data demonstrate that
      GHRP-2 failed to reverse the severe GHD caused by lack of GHRH.

PMID- 15985454
TI  - Corticosteroid-regulated genes in rat kidney: mining time series array data.
AB  - Kidney is a major target for adverse effects associated with corticosteroids. A
      microarray dataset was generated to examine changes in gene expression in rat
      kidney in response to methylprednisolone. Four control and 48 drug-treated
      animals were killed at 16 times after drug administration. Kidney RNA was used to
      query 52 individual Affymetrix chips, generating data for 15,967 different probe
      sets for each chip. Mining techniques applicable to time series data that
      identify drug-regulated changes in gene expression were applied. Four sequential
      filters eliminated probe sets that were not expressed in the tissue, not
      regulated by drug, or did not meet defined quality control standards. These
      filters eliminated 14,890 probe sets (94%) from further consideration.
      Application of judiciously chosen filters is an effective tool for data mining of
      time series datasets. The remaining data can then be further analyzed by
      clustering and mathematical modeling. Initial analysis of this filtered dataset
      identified a group of genes whose pattern of regulation was highly correlated
      with prototype corticosteroid enhanced genes. Twenty genes in this group, as well
      as selected genes exhibiting either downregulation or no regulation, were
      analyzed for 5' GRE half-sites conserved across species. In general, the results
      support the hypothesis that the existence of conserved DNA binding sites can
      serve as an important adjunct to purely analytic approaches to clustering genes
      into groups with common mechanisms of regulation. This dataset, as well as
      similar datasets on liver and muscle, are available online in a format amenable
      to further analysis by others.

PMID- 15985455
TI  - Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain
      medullary dorsal vagal complex in rats.
AB  - Hypo- or hyperthyroidism is associated with autonomic disorders. We studied Fos
      expression in the medullary dorsal motor nucleus of the vagus (DMV), nucleus
      tractus solitarii (NTS), and area postrema (AP) in four groups of rats with
      different thyroid states induced by a combination of drinking water and daily
      intraperitoneal injection for 1-4 wk: 1) tap water and vehicle; 2) 0.1%
      propylthiouracil (PTU) and vehicle; 3) PTU and thyroxine (T4; 2 microg/100 g);
      and 4) tap water and T4 (10 microg/100 g). The numbers of Fos immunoreactive (IR)
      positive neurons in the DMV, NTS, and AP were low in euthyroid rats but
      significantly higher in the 4-wk duration in hypothyroid rats, which were
      prevented by simultaneous T4 replacement. Hyperthyroidism had no effect on Fos
      expression in these areas. There were significant negative correlations between
      T4 levels and the numbers of Fos-IR-positive neurons in the DMV (r = -0.6388, P <
      0.008), NTS (r = -0.6741, P < 0.003), and AP (r = -0.5622, P < 0.004). Double
      staining showed that Fos immunoreactivity in the DMV of hypothyroid rats was
      mostly localized in choline acetyltransferase-containing neurons. Thyroid hormone
      receptors alpha1 and beta2 were localized in the observed nuclei. These results
      indicate that thyroid hormone influences the DMV/NTS/AP neuronal activity, which
      may contribute to the vagal-related visceral disorders observed in
      hypothyroidism.

PMID- 15985456
TI  - Endothelial t-PA release is impaired in overweight and obese adults but can be
      improved with regular aerobic exercise.
AB  - Endothelial release of tissue-type plasminogen activator (t-PA) regulates
      fibrinolysis and is considered to be a primary endogenous defense mechanism
      against thrombosis. Adiposity is associated with an increased risk of
      atherothrombotic events. We determined the influence of overweight and obesity on
      the capacity of the vascular endothelium to release t-PA and the effects of
      regular aerobic exercise on endothelial t-PA release in previously sedentary
      overweight and obese adults. First, we studied 66 sedentary adults: 28 normal
      weight (BMI < 25 kg/m2); 22 overweight (BMI > or = 25 and < 30 kg/m2); and 16
      obese (BMI > or = 30 kg/m2). Net endothelial t-PA release was determined in vivo
      in response to intrabrachial infusions of bradykinin (BK) and sodium
      nitroprusside. Second, we studied 17 overweight and obese adults who completed a
      3-mo aerobic exercise intervention. Net release of t-PA in response to BK was
      approximately 45% lower (P < 0.01) in overweight (from 0.1 +/- 0.4 to 41.7 +/-
      4.9 ng x 100 ml tissue(-1) x min(-1)) and obese (-0.1 +/- 0.6 to 47.7 +/- 5.2 ng
      x 100 ml tissue(-1) x min(-1)) compared with normal-weight (0.1 +/- 0.8 to 77.5
      +/- 6.7 ng x 100 ml tissue(-1) x min(-1)) adults. There was no difference in t-PA
      release between the overweight and obese groups. Exercise training significantly
      increased t-PA release capacity in overweight and obese adults (from -0.3 +/- 0.5
      to 37.1 +/- 4.9 ng x 100 ml tissue(-1) x min(-1) before training vs. 1.0 +/- 0.9
      to 65.4 +/- 6.3 ng x 100 ml tissue(-1) x min(-1) after training) to levels
      comparable with those of their normal-weight peers. These results indicate that
      overweight and obesity are associated with profound endothelial fibrinolytic
      dysfunction. Importantly, however, regular aerobic exercise can increase the
      capacity of the endothelium to release t-PA in this at-risk population.

PMID- 15985458
TI  - Public health journals in own languages: an endangered species?

PMID- 15985459
TI  - Income inequality and alcohol use: a multilevel analysis of drinking and
      drunkenness in adolescents in 34 countries.
AB  - BACKGROUND: Economic inequality has been hypothesized to be a health determinant,
      independent of poverty and household income. The goal of this study was to
      explore the contextual influences of income inequality on alcohol use and
      frequency of drunkenness in adolescents. METHODS: The Health Behaviour in School
      aged Children study surveyed 162 305 adolescents (ages 11, 13 and 15 years) in 34
      countries, providing self-report data on family affluence, alcohol consumption
      and episodes of drunkenness. Country-level data on income inequality and overall
      wealth were retrieved from the United Nations Development Program. RESULTS:
      Multilevel logistic regression revealed that 11- and 13-year-olds in countries of
      high income inequality consumed more alcohol than their counterparts in countries
      of low income inequality (after adjustment for sex, family affluence and country
      wealth). No such effect on alcohol consumption was found in 15-year-olds. Eleven
      year-olds in countries of high income inequality reported more episodes of
      drunkenness than their counterparts in countries of low income inequality. No
      such effect of income inequality on drunkenness was found in 13- or 15-year-olds.
      CONCLUSIONS: Income inequality may have a contextual influence on the use of
      alcohol among younger adolescents. Findings suggest that economic policies that
      affect the distribution of wealth within societies may indirectly influence the
      use of alcohol during early and mid-adolescence.

PMID- 15985460
TI  - Saying is not (always) doing: cigarette warning labels are useless.

PMID- 15985462
TI  - Non-canonical YXXGPhi endocytic motifs: recognition by AP2 and preferential
      utilization in P2X4 receptors.
AB  - During clathrin-mediated endocytosis, proteins on the cell surface are selected
      for inclusion in clathrin-coated vesicles by clathrin adaptors, mainly the
      adaptor complex AP2. The P2X4 subtype of ATP-gated ion channel has in its C
      terminus two putative endocytic motifs: a canonical YXXPhi motif and a non
      canonical YXXGPhi motif (YEQGL). We demonstrate that endocytosis of P2X4
      receptors is mediated preferentially by the YXXGPhi motif because the YXXPhi
      motif is inaccessible to AP2 owing to the structure of the channel. The crystal
      structure of a complex between residues 160-435 of the mu2 subunit of AP2 and a
      P2X4 C-terminal peptide showed that the YEQGL motif binds to mu2 at the same site
      as YXXPhi motifs. Y and Phi residues are accommodated in the same hydrophobic
      pockets in mu2 with the extra residue between them being accommodated by changes
      in the peptide's backbone configuration, when compared to YXXPhi motifs. These
      data demonstrate that the family of potential tyrosine-based endocytic signals
      must be expanded to include motifs with an additional glycine at Y+3 (YXXGPhi).

PMID- 15985463
TI  - Mutational analysis of action of mitochondrial fusion factor mitofusin-2.
AB  - Mitofusin-2 (Mfn2) is an essential component of mitochondrial fusion machinery,
      but its molecular mechanism of action is not clear. We found that a Mfn2 deletion
      mutant lacking two transmembrane spans (Mfn(DeltaTM)) acts as a dominant-negative
      mutant and blocks mitochondrial fusion. Furthermore, detailed analysis of various
      mutants of Mfn(DeltaTM) revealed that GTPase activity and four regions highly
      conserved from nematodes to mammals are necessary for the dominant-negative
      effect. Immunoprecipitation studies of the N- and C-terminal cytosolic tails of
      Mfn2 showed that in addition to the coiled-coil domains previously identified, a
      highly conserved domain in the most N-terminal region and GTPase activity are
      necessary for the interaction between the N- and C-terminal tails, which is in
      turn required for the dominant-negative effect. In addition, we found
      unexpectedly that overexpression of the deletion mutant composed of one short
      region each in the N- and C-terminal tails of Mfn2 resulted in loss of
      mitochondrial membrane potential, suggesting that Mfn2 might also be connected to
      maintenance of mitochondrial membrane potential.

PMID- 15985464
TI  - The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death.
AB  - Autophagic cell death is morphologically characterized by an accumulation of
      autophagic vacuoles. Here, we show that inactivation of LAMP2 by RNA interference
      or by homologous recombination leads to autophagic vacuolization in nutrient
      depleted cells. Cells that lack LAMP2 expression showed an enhanced accumulation
      of vacuoles carrying the marker LC3, yet a decreased colocalization of LC3 and
      lysosomes, suggesting that the fusion between autophagic vacuoles and lysosomes
      was inhibited. While a fraction of mitochondria from starved LAMP2-expressing
      cells colocalized with lysosomal markers, within autophagolysosomes, no such
      colocalization was found on removal of LAMP2 from the experimental system. Of
      note, LAMP1 depletion had no such effects and did not aggravate the phenotype
      induced by LAMP2-specific small interfering RNA. Serum and amino acid-starved
      LAMP2-negative cells exhibited an accumulation of autophagic vacuoles and then
      succumbed to cell death with hallmarks of apoptosis such as loss of the
      mitochondrial transmembrane potential, caspase activation and chromatin
      condensation. While caspase inhibition retarded cell death, it had no protective
      effect on mitochondria. Stabilization of mitochondria by overexpression of Bcl-2
      or the mitochondrion-targeted cytomegalovirus protein vMIA, however, blocked all
      signs of apoptosis. Neither caspase inhibition nor mitochondrial stabilization
      antagonized autophagic vacuolization in LAMP2-deficient cells. Altogether, these
      data indicate that accumulation of autophagic vacuoles can precede apoptotic cell
      death. These findings argue against the clear-cut distinction between type 1
      (apoptotic) and type 2 (autophagic) cell death.

PMID- 15985465
TI  - N-WASP deficiency impairs EGF internalization and actin assembly at clathrin
      coated pits.
AB  - WASP and WAVE family proteins promote actin polymerization by stimulating Arp2/3
      complex-dependent filament nucleation. Unlike WAVE proteins, which are known to
      drive the formation of protrusions such as lamellipodia and membrane ruffles,
      vertebrate cell functions of WASP or N-WASP are less well established. Recent
      work demonstrated that clathrin-coated pit invagination can coincide with
      assembly of actin filaments and with accumulation of N-WASP and Arp2/3 complex,
      but the relevance of their recruitment has remained poorly defined. We employed
      two-colour total internal reflection microscopy to study the recruitment and
      dynamics of various components of the actin polymerization machinery and the
      epidermal growth factor receptor signalling machinery during clathrin-coated pit
      internalization in control cells and cells genetically deficient for functional N
      WASP. We found that clathrin-coated pit endocytosis coincides with the
      recruitment of N-WASP, Arp2/3 complex and associated proteins, but not of WAVE
      family members. Actin accumulation at clathrin-coated pits requires the Arp2/3
      complex, since Arp2/3 complex sequestration in the cytosol abolished any
      detectable actin assembly. The absence of N-WASP caused a significant reduction
      in the frequencies of actin and Arp2/3 complex accumulations at sites of clathrin
      coated pit invagination and vesicle departure. Although N-WASP was not essential
      for Arp2/3-complex-mediated actin assembly at these sites or for EGF receptor
      mediated endocytosis, N-WASP deficiency caused a marked reduction of EGF
      internalization. We conclude that the assembly of WASP subfamily proteins and
      associated factors at sites of clathrin-coated pit invagination amplifies actin
      accumulations at these sites promoting efficient internalization of ligands via
      clathrin-mediated endocytosis.

PMID- 15985466
TI  - Cell-cycle-dependent resistance to Bacillus thuringiensis Cry1C toxin in Sf9
      cells.
AB  - The Sf9 cell line, derived from the moth Spodoptera frugiperda, is highly and
      specifically sensitive to the Bacillus thuringiensis Cry1C toxin. Upon exposure
      to Cry1C, ionic pores are formed in the plasma membrane leading to cell swelling
      and death. Here, we describe a unique transient tolerance to Cry1C of dividing
      cells, which allowed completion of the division process in the presence of Cry1C.
      Correlatively, arresting the cells at G2-M phase by nocodazole treatment rendered
      them insensitive to Cry1C. When the arresting agent was removed, the cells
      completed their division and gradually regained Cry1C sensitivity. In comparison
      to normal cells with 1-2% cell-division frequency, the M-phase arrested cells
      bound less toxin in binding assays. Moreover, no lipid rafts could be isolated
      from the membranes of M-phase arrested cells. Caveolin-1, identified here for the
      first time in insect cells, was immunodetected as a lipid raft component of
      normal cells, but was only present in the membrane-soluble fraction of G2-M
      arrested cells. Thus M-phase-linked changes in lipid raft organization may
      account for diminished Cry1C binding and toxicity. Furthermore, considering the
      pivotal role of lipid rafts in different cell functions of many cell types, the
      lack of organized lipid rafts in dividing cells may transiently affect cell
      susceptibility to pathogens, toxins and other lipid raft-linked functions.

PMID- 15985467
TI  - Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis
      enhancing lysophospholipase D.
AB  - Autotaxin (NPP2) is an extracellular protein that is upregulated in various
      malignancies, including breast and lung cancer. It potently stimulates cell
      proliferation, cell motility and angiogenesis, which is accounted for by its
      intrinsic lysophospholipase-D activity that generates the lipid mediators
      lysophosphatidic acid and sphingosine-1-phosphate. Based on its structural
      similarities with the better characterized nucleotide
      pyrophosphatase/phosphodiesterase NPP1, it has always been assumed that NPP2 is
      also synthesized as a type-II integral membrane protein and that extracellular
      NPP2 is generated from this membrane precursor. We show here, however, using
      domain swapping and mutagenesis experiments as well as N-terminal protein
      sequencing, that NPP2 is actually synthesized as a pre-pro-enzyme and that the
      proteolytically processed protein is secreted. Following the removal of a 27
      residue signal peptide by the signal peptidase, NPP2 is subsequently cleaved by
      proprotein convertases (PCs). The removal of an N-terminal octapeptide by PCs is
      associated with an enhanced activity of NPP2 as a lysophospholipase D. These
      novel insights in the maturation of NPP2 have also implications for the
      development of NPP2 inhibitors as potential anti-cancer agents.

PMID- 15985468
TI  - Mobility of proteins associated with the plasma membrane by interaction with
      inositol lipids.
AB  - Translocation of a protein to the plasma membrane in response to the generation
      of polyphosphoinositol lipids is believed to be an important component of
      cellular regulation, in part because it increases the effective concentration of
      that protein relative to other proteins in the same membrane by restricting it to
      a two-dimensional space. However, such a concept assumes that, once translocated,
      a protein retains the free mobility it had in the cytoplasm, and also that the
      possible existence of partitioned pools of inositol lipids does not restrict its
      sphere of influence. We have explored by fluorescence recovery after
      photobleaching (FRAP) the mobility of four green-fluorescent-protein-tagged
      proteins, GAP1(IP4BP) and GAP1(m), when they are either cytoplasmic or attached
      to the plasma membrane, and the PH domain of PI-PLCdelta(1) and ICAM as
      representative of, respectively, another inositol-lipid-anchored protein and a
      single-transmembrane-span-domain protein. The data from GAP1(m) and the PI
      PLCdelta(1) PH domain show that, when proteins associate with inositol lipids in
      the plasma membrane, they retain a mobility similar to that in the cytoplasm, and
      probably also similar to the inositol lipid to which they are attached,
      suggesting a free diffusion within the plane of the membrane. Moreover, this free
      diffusion is similar whether they are bound to PtdIns(3,4,5)P(3) or to
      PtdIns(4,5)P(2), and no evidence was found by these criteria for restricted pools
      of PtdIns(4,5)P(2). The mobility of GAP1(IP4BP), which has been reported to
      associate with PtdIns(4,5)P(2) in the plasma membrane, is much lower, suggesting
      that it might interact with other cellular components. Moreover, the mobility of
      GAP1(IP4BP) is not detectably altered by the generation of either of its two
      potential regulators, Ins(1,3,4,5)P(4) or PtdIns(3,4,5)P(3).

PMID- 15985469
TI  - The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian
      cells.
AB  - Mitochondria are dynamic organelles that change morphology by controlled fission
      and fusion events. Mitochondrial fission is regulated by a conserved protein
      complex assembled at the outer membrane. Human MTP18 is a novel nuclear-encoded
      mitochondrial membrane protein, implicated in controlling mitochondrial fission.
      Upon overexpression of MTP18, mitochondrial morphology was altered from
      filamentous to punctate structures suggesting excessive mitochondrial fission.
      Mitochondrial fragmentation was blocked in cells coexpressing either the
      mitochondrial fusion protein Mfn1 or Drp1(K38A), a dominant negative version of
      the fission protein Drp1. Also, a loss-of function of endogenous MTP18 by RNA
      interference (RNAi) resulted in highly fused mitochondria. Moreover, MTP18
      appears to be required for mitochondrial fission because it is blocked after
      overexpression of hFis1 in cells with RNAi-mediated MTP18 knockdown. In
      conclusion, we propose that MTP18 functions as an essential intramitochondrial
      component of the mitochondrial division apparatus, contributing to the
      maintenance of mitochondrial morphology.

PMID- 15985470
TI  - Stability of bortezomib 1-mg/mL solution in plastic syringe and glass vial.
AB  - BACKGROUND: The proteasome inhibitor bortezomib (BTZ), used in antineoplastic
      chemotherapy, must be diluted in NaCl 0.9% for injection and stored for no more
      than 3 hours in a syringe or 8 hours in a vial. Better information on its
      stability could improve storage. OBJECTIVE: To assess the stability of BTZ
      solution (1 mg/mL) in syringes and vials. METHODS: BTZ 1-mg/mL solutions were
      prepared by adding sterile NaCl 0.9% to Velcade vials containing 3.5 mg of
      lyophilized BTZ. Syringes were filled with 1 mL of solution and stored in the
      dark at 5 degrees C or 60 degrees C; others were not protected from light and
      stored at 22 degrees C. Velcade vials containing 1 mL of solution were stored at
      5 degrees C in the dark. Samples were taken at various times over 23 days and
      assayed in duplicate. An HPLC method for assaying the stability of BTZ was
      validated. Appearance and pH were recorded. RESULTS: There was no color change or
      precipitation in the samples, and the pH was stable. Oxidation, light, and
      storage temperature all affected the chemical stability of BTZ. The mean
      concentrations of BTZ in syringes stored for 2, 3, and 5 days at 60, 22, and 5
      degrees C were >95% of the initial concentration. The mean concentration of BTZ
      in vials stored for 5 days at 5 degrees C was >95% of the initial concentration.
      CONCLUSIONS: BTZ stored refrigerated in vials or syringes and protected from
      light is chemically stable for 5 days after reconstitution.

PMID- 15985471
TI  - Effect of prophylactic amiodarone on clinical and economic outcomes after
      cardiothoracic surgery: a meta-analysis.
AB  - BACKGROUND: Two previous meta-analyses of amiodarone for prevention of
      postoperative atrial fibrillation (POAF) after cardiothoracic surgery did not
      evaluate total hospital cost, concluded that data on stroke are incomplete, and
      did not evaluate the effect of clinical heterogeneity between trials. OBJECTIVE:
      To conduct a meta-analysis examining amiodarone's prophylactic impact on
      cardiothoracic surgery POAF, length of stay (LOS), stroke, and total costs.
      METHODS: Three reviewers conducted a systematic literature search of MEDLINE,
      EMBASE, CINAHL, and the Cochrane Library (1966-SEPTEMBER 2004). Studies were
      included if they met the following criteria: (1) randomized controlled trial
      versus placebo/routine treatment, (2) coronary artery bypass graft and/or
      valvular surgery, (3) Jadad score > or = 3, (4) reported data on incidence of
      POAF or stroke, LOS, or total costs, (5) used electrocardiographic/Holter
      monitoring, and (6) monitored subjects for > or = 2 days. A random-effects model
      was utilized. Subgroup and sensitivity analyses were conducted. RESULTS: Fifteen
      trials were identified, including 1512 and 1429 patients in the amiodarone and
      control groups, respectively. Amiodarone reduced POAF (OR 0.50; 95% CI 0.42 to
      0.60) and decreased stroke (n = 8 studies), LOS (n = 10), and total costs (n = 6)
      (OR 0.47; 95% CI 0.23 to 0.96; -0.73 days, 95% CI -0.95 to -0.51; and -dollar
      1619, 95% CI -3395 to 156, respectively). Surgery type, beta-blocker use, route
      of administration, use of a fixed-effects model, or exclusion of
      unblinded/unpublished studies did not affect the overall results. No statistical
      heterogeneity was observed for any endpoint evaluated (p > 0.22 for all
      comparisons). CONCLUSIONS: Prophylactic treatment with amiodarone decreases
      patients' risk of POAF and stroke while reducing LOS.

PMID- 15985472
TI  - Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on
      the management of patients with differentiated thyroid carcinomas.
AB  - CONTEXT: Changes in thyroglobulin (Tg) and/or Tg antibody (TgAb) methods can
      disrupt the serial monitoring of differentiated thyroid carcinoma (DTC) patients.
      OBJECTIVE: This study compared Tg measurements made in TgAb-negative and TgAb
      positive sera using four RIA and 10 immunometric assay (IMA) methods. DESIGN:
      TgAb detection using a panel of 12 direct methods was contrasted with four Tg
      recovery tests. Sera from 110 normal euthyroid subjects (68 TgAb negative/42 TgAb
      positive) and 131 TgAb-negative DTC patients had Tg and/or TgAb analyses made by
      10 laboratories in four countries. Euthyroid controls were used to compare Tg and
      TgAb ranges, sensitivities, and TgAb interference, whereas DTC patients were used
      to study Tg assay specificities, hook effects, and the influence of high Tg
      levels on TgAb measurements. RESULTS: Tg methods had high between-method
      variability [47 +/- 3% (+/-sem)] that was only marginally reduced by CRM-457
      standardization (37 +/- 3%). All methods had suboptimal sensitivity, and some
      failed to detect Tg in some normal euthyroid controls. Although direct TgAb
      measurements were more reliable than exogenous recovery tests, TgAb status was
      only concordant in 65% of sera. Only four of 42 (9.5%) sera containing TgAb had
      antibody detected by all direct methods. All IMA methods reported paradoxically
      undetectable Tg for many TgAb-positive euthyroid controls, suggesting TgAb
      interference, whereas RIA methods reported appropriate normal range values for
      these same subjects. Some sera displaying interference had TgAb detected by only
      a minority of methods. CONCLUSIONS: Specificity differences, suboptimal
      sensitivity, hook effects, and an inability to reliably detect interfering TgAb
      compromise the clinical utility of current Tg and TgAb methods. All of the IMA
      methods were prone to underestimate serum Tg in the presence of TgAb, whereas the
      RIA methods appeared resistant to TgAb interference.

PMID- 15985473
TI  - Contribution of selective HLA-DRB1/DQB1 alleles and haplotypes to the genetic
      susceptibility of type 1 diabetes among Lebanese and Bahraini Arabs.
AB  - CONTEXT: Human leukocyte antigen (HLA) class II genes contribute to the genetic
      susceptibility of type 1 diabetes (T1D), and both susceptible and protective
      alleles were implicated with its pathogenesis, which varies among various
      ethnic/racial groups. OBJECTIVE: This study investigated the heterogeneity in HLA
      class II haplotypes distribution among Bahraini and Lebanese T1D patients.
      DESIGN: This was a cross-sectional retrospective study. SETTING: The study was
      conducted at primary care private and public health centers. PATIENTS AND OTHER
      PARTICIPANTS: Subjects comprised 126 T1D patients and 126 healthy controls from
      Bahrain and 78 Lebanese T1D patients and 111 control subjects. INTERVENTION(S):
      There were no interventions. RESULTS: Although Lebanese and Bahraini patients
      share DRB1*030101, DQB1*0201 as susceptible and DRB1*100101 and DQB1*030101 as
      protective alleles, DRB1*040101 was an additional susceptible allele in Bahraini
      patients, and DRB1*130701 and DQB1*050101 were additional susceptible and
      protective alleles in Lebanese, respectively. DRB1*030101-DQB1*0201 was
      susceptible, whereas DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 were
      protective haplotypes in Bahraini and Lebanese. DRB1*040101-DQB1*0302 and
      DRB1*040101-DQB1*050101 displayed different associations: they were protective in
      Lebanese but susceptible or neutral among Bahrainis. Whereas the frequency of
      homozygous DRB1*03011-DQB1*0201 was higher in Bahraini and to a lesser extent
      Lebanese patients, homozygous DRB1*110101-DQB1*030101 was significantly more
      frequent in Lebanese but not Bahraini controls, whereas DRB1*030101
      DQB1*0201/DRB1*040101-DQB1*0201 was the major genotype among Bahraini patients
      but not Lebanese subjects in whom it was present at very low frequencies.
      CONCLUSION: In view of these differences between Bahraini and Lebanese, this
      demonstrates that the contribution of HLA class II to the genetic susceptibility
      to T1D must be evaluated with regard to specific HLA haplotypes and also ethnic
      origin and racial background.

PMID- 15985474
TI  - Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and
      impact of interleukin-6 levels and intubation with etomidate on adrenal function
      and mortality.
AB  - CONTEXT: Adequate adrenal function is pivotal to survive meningococcal sepsis.
      OBJECTIVES: The objective of the study was to evaluate adrenocortical function in
      meningococcal disease. DESIGN: This was an observational cohort study. SETTING:
      The study was conducted at a university-affiliated pediatric intensive care unit.
      PATIENTS: Sixty children with meningococcal sepsis or septic shock participated
      in the study. MAIN OUTCOME MEASURES: The differences in adrenal function between
      nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on
      pediatric intensive care unit admission were measured. RESULTS: Nonsurvivors had
      significantly lower median cortisol to ACTH ratio than shock survivors and sepsis
      survivors. Because cortisol binding globulin and albumin levels did not
      significantly differ among the groups, bioavailable cortisol levels were also
      significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had
      significantly lower cortisol to 11-deoxycortisol ratios but not lower 11
      deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple
      regression analysis, decreased cortisol to ACTH ratio was significantly related
      to higher IL-6 levels and intubation with etomidate (one single bolus), whereas
      decreased cortisol to 11-deoxycortisol ratio was significantly related only to
      intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors
      than shock survivors, whereas plasma renin activity did not significantly differ.
      CONCLUSIONS: Our study shows that the most severely ill children with septic
      shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not
      more informative on adrenal function than total cortisol levels. Besides disease
      severity, one single bolus of etomidate during intubation was related to
      decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal
      function was not related to decreased 21-hydroxylase activity. Based on our
      results, it seems of vital importance to take considerable caution using
      etomidate and consider combining its administration with glucocorticoids during
      intubation of children with septic shock.

PMID- 15985475
TI  - PTPN11 mutations are associated with mild growth hormone resistance in
      individuals with Noonan syndrome.
AB  - CONTEXT: Noonan syndrome is frequently associated with an unclear disturbance of
      GH secretion. Half the individuals with Noonan syndrome carry a heterozygous
      mutation of the nonreceptor-type protein tyrosine phosphatase, Src homology
      region 2-domain phosphatase-2 (SHP-2), encoded by PTPN11, which has a role in GH
      receptor signaling. OBJECTIVE: The objective of this study was to compare GH
      secretion and IGF-I/IGF-binding protein-3 (IGFBP-3) levels of the SHP-2 mutation
      positive (mut+ group) vs. mutation-negative individuals (mut- group). DESIGN,
      SETTING, AND PATIENTS: All children presenting to us with short stature plus at
      least three typical anomalies of Noonan syndrome or pulmonic stenosis during the
      last 5 yr (n = 29; 10 females and 19 males) were recruited. Auxological data,
      dysmorphic features, and cardiac morphology were documented. Hormone levels were
      measured by RIA. All coding exons of PTPN11 were sequenced after PCR
      amplification. INTERVENTION: A prepubertal subgroup (n = 11) was treated with
      recombinant human GH (rhGH) to promote growth. RESULTS: Sequencing yielded 11
      different PTPN11 missense mutations in 16 of the 29 patients (55% mut+). Pulmonic
      stenosis (81 vs. 15%; P = 0.0007) and septal defects (63 vs. 15%; P = 0.02) were
      more frequently found in the mut+ group, whereas minor anomalies, cryptorchidism,
      and learning disabilities were as frequent in the mut+ group as in the mut-
      group. The mut+ group was younger at presentation (mean +/- sd, 5.1 +/- 2.7 vs.
      10.3 +/- 5.2 yr; P = 0.002), but not significantly shorter [-3.15 +/- 0.92 vs. 
      3.01 +/- 1.35 height sd score (SDS)]. IGF-I levels (-2.03 +/- 0.69 vs. -1.13 +/-
      0.89 SDS; P = 0.005) and IGFBP-3 levels (-0.92 +/- 1.26 vs. 0.40 +/- 1.08 SDS; P
      = 0.006) were significantly lower in the mut+ group. In contrast, GH levels
      showed a tendency to be higher in the mut+ group during spontaneous secretion at
      night and arginine stimulation (P > or = 0.075, not significant). The mean change
      in height SDS after 1 yr of rhGH therapy (0.043 mg/kg.d) was +0.66 +/- 0.21 in
      the mut+ group (n = 8), but +1.26 +/- 0.36 in the mut- group (n = 3; P = 0.007).
      CONCLUSIONS: Our data suggest that SHP-2 mutations in Noonan syndrome cause mild
      GH resistance by a postreceptor signaling defect, which seems to be partially
      compensated for by elevated GH secretion. This defect may contribute to the short
      stature phenotype in children with SHP-2 mutations and their relatively poor
      response to rhGH.

PMID- 15985476
TI  - A novel mutation L260P of the steroidogenic acute regulatory protein gene in
      three unrelated patients of Swiss ancestry with congenital lipoid adrenal
      hyperplasia.
AB  - CONTEXT: Lipoid congenital adrenal hyperplasia (CAH) is the most severe form of
      CAH leading to impaired production of all adrenal and gonadal steroids. Mutations
      in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid
      CAH. OBJECTIVE: We investigated three unrelated patients of Swiss ancestry who
      all carried novel mutations in the StAR gene. All three subjects were phenotypic
      females with absent Mullerian derivatives, 46,XY karyotype, and presented with
      adrenal failure. METHODS AND RESULTS: StAR gene analysis showed that one patient
      was homozygous and the other two were heterozygous for the novel missense
      mutation L260P. Of the heterozygote patients, one carried the novel missense
      mutation L157P and one had a novel frameshift mutation (629-630delCT) on the
      second allele. The functional ability of all three StAR mutations to promote
      pregnenolone production was severely attenuated in COS-1 cells transfected with
      the cholesterol side-chain cleavage system and mutant vs. wild-type StAR
      expression vectors. CONCLUSIONS: These cases highlight the importance of StAR
      dependent steroidogenesis during fetal development and early infancy; expand the
      geographic distribution of this condition; and finally establish a new, prevalent
      StAR mutation (L260P) for the Swiss population.

PMID- 15985477
TI  - Expression profiles for steroidogenic enzymes in adrenocortical disease.
AB  - CONTEXT: Excess production of aldosterone or cortisol has profound effects on
      cardiovascular function and impacts other major organ systems. The mechanisms
      leading to the autonomous hypersecretion of aldosterone or cortisol in
      aldosterone-producing adenoma (APA) or cortisol-producing adenoma (CPA) are
      unknown. OBJECTIVE: The objective of this study was to compare the expression
      profiles of several steroid-metabolizing enzymes and transcription factors from
      normal adrenal (NA), APAs, and CPAs. DESIGN: RNA from NAs, APAs, and CPAs were
      analyzed by microarray and real-time RT-PCR. SETTING: This study was performed at
      academic research laboratories. PATIENTS: At least nine normal controls and 12
      patients with APA or CPA were studied. INTERVENTION: There was no intervention
      procedure. MAIN OUTCOME MEASURE: The main outcome measure was the expression of
      steroidogenic enzymes in adrenocortical disease. RESULTS: A microarray indicated
      a greater than 3-fold increase in the expression of CYP11B2 (aldosterone
      synthase) in APA, whereas 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)
      and HSD17B1 had greater than 3-fold increases in expression in CPA compared with
      NA. Real-time RT-PCR showed that APAs produced higher levels of HSD3B2, CYP21 (21
      hydroxylase), and CYP11B2 mRNA, whereas CPAs produced higher levels of CYP11A
      (cholesterol side-chain cleavage), CYP17 (17alpha-hydroxylase/17-20 lyase),
      HSD3B2, and CYP11B1 (11beta-hydroxylase) mRNA compared with normal adrenal.
      Steroidogenic factor-1, DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia
      congenita, critical region on the X chromosome gene 1), and GATA-6 were expressed
      at higher levels in APAs and CPAs, whereas NURR1 was expressed at higher levels
      in APAs than in CPAs or NAs. CONCLUSION: Elevated production of aldosterone in
      APAs and of cortisol in CPAs is associated with increased expression of enzymes
      needed for corticosteroid production along with alterations in transcription
      factors that enhance the expression of steroid-metabolizing enzymes.

PMID- 15985478
TI  - Inhibition of cortisol biosynthesis decreases circulating leptin levels in obese
      humans.
AB  - CONTEXT: Glucocorticoids increase both appetite and leptin secretion; the
      hyperleptinemic effect might be a counterregulatory response to the orexigenic
      effect of glucocorticoids. However, the effect of glucocorticoid inhibition on
      leptin production has not been reported. OBJECTIVE: We tested the hypothesis that
      if glucocorticoid-induced hyperleptinemia plays a physiological role, then
      inhibition of endogenous cortisol biosynthesis should decrease leptin secretion.
      DESIGN: A randomized, placebo-controlled, cross-over study design was used.
      SETTING: The study was carried out at a General Clinical Research Center.
      PARTICIPANTS: Eight obese subjects (four men, four women; mean age, 30.4 +/- 1.56
      yr; mean body mass index, 42.0 +/- 1.33 kg/m2) participated in the study.
      INTERVENTION: The subjects were treated with metyrapone (750 mg every 4 h) or
      placebo for 24 h during two overnight admissions, 2 wk apart. Blood sampling for
      measurement of cortisol, leptin glucose, insulin, and C-peptide was performed
      hourly for 6 h and every 2 h for 24 h. MAIN OUTCOME MEASURE: The change in plasma
      leptin from baseline during metyrapone vs. placebo treatment was measured.
      RESULTS: Metyrapone treatment was associated with a significant decrease in
      plasma cortisol level; the cortisol nadir was 4.84 +/- 1.22 microg/dl during
      placebo and 2.80 +/- 0.65 microg/dl during metyrapone treatment (P = 0.009).
      Compared with placebo, metyrapone treatment was associated with a significant
      reduction in circulating leptin levels and marked attenuation of the nocturnal
      rise in plasma leptin (+28.45 +/- 11.12% vs. +55.51 +/- 5.42%; P = 0.01).
      CONCLUSIONS: We conclude that metyrapone-induced inhibition of cortisol
      biosynthesis results in hypoleptinemia, which indicates that glucocorticoids may
      play an important role in the physiological regulation of leptin.

PMID- 15985479
TI  - Hyperglycemia alters tumor necrosis factor-alpha release from mononuclear cells
      in women with polycystic ovary syndrome.
AB  - CONTEXT: Women with polycystic ovary syndrome (PCOS) are often insulin resistant
      and have chronic low-level inflammation. OBJECTIVE: The purpose of this study was
      to determine the effects of hyperglycemia on lipopolysaccharide (LPS)-stimulated
      TNFalpha release from mononuclear cells (MNC) in PCOS. DESIGN: The study was
      designed as a prospective controlled study. SETTING: The study was carried out at
      an academic medical center. PATIENTS: Sixteen reproductive age women with PCOS
      (eight lean, eight obese) and 14 age-matched controls (eight lean, six obese)
      participated in the study. MAIN OUTCOME MEASURES: Insulin sensitivity (IS) was
      derived from a 2-h 75-g oral glucose tolerance test (IS(OGTT)). Percentage of
      truncal fat was determined by dual-energy absorptiometry. TNFalpha release was
      measured from MNC cultured in the presence of LPS from blood samples drawn
      fasting and 2 h after glucose ingestion. RESULTS: IS(OGTT) was lower in women
      with PCOS compared with controls (3.9 +/- 0.4 vs. 6.3 +/- 1.0; P < 0.03) and was
      negatively correlated with percentage of truncal fat (r = 0.56; P < 0.002).
      Truncal fat was greater in lean women with PCOS compared with lean controls (29.8
      +/- 2.6 vs. 23.8 +/- 2.5%; P < 0.04). The TNFalpha response was different between
      obese and lean controls (-96.9 +/- 21.2 vs. 24.4 +/- 21.6 pg/ml; P < 0.03) and
      obese and lean women with PCOS (-94.1 +/- 34.5 vs. 30.4 +/- 17.6 pg/ml; P <
      0.002). Fasting plasma C-reactive protein was elevated (P < 0.003) in obese PCOS
      and obese controls compared with lean controls. CONCLUSION: An increase in
      abdominal adiposity and increased TNFalpha release from MNC after hyperglycemia
      may contribute to insulin resistance in lean PCOS patients. In contrast, obese
      PCOS patients have more profound chronic inflammation, and thus may have LPS
      tolerance that protects them from relatively mild excursions in blood glucose.

PMID- 15985480
TI  - Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening
      without endothelial dysfunction.
AB  - CONTEXT: Women with Turner syndrome (TS) have an increased cardiovascular
      mortality rate from both structural and ischemic heart disease, especially aortic
      dissection. OBJECTIVE: We hypothesized that TS women have a fundamental arterial
      wall defect that may be due to genetic factors or estrogen deficiency. DESIGN,
      SETTING, AND PATIENTS: TS women (n = 93) were compared with normal controls (n =
      25) and women with 46,XX primary amenorrhea (PA) (n = 11) with a similar history
      of estrogen deficiency. Clinical parameters, aortic root diameter, extraaortic
      arterial structure [common carotid (CD), brachial artery diameter, and carotid
      intima-media thickness (IMT)], arterial stiffness (pulse-wave velocity,
      augmentation index), and endothelial function (flow-mediated dilatation) were
      assessed. MAIN OUTCOME MEASURES: These included arterial diameters and vascular
      physiology parameters. RESULTS: Differences in arterial structure were observed
      among TS, normal controls, and 46,XX PA women: IMT (0.61 +/- 0.07 vs. 0.55 +/-
      0.06 vs. 0.60 +/- 0.05 mm, respectively; P < 0.001), CD (5.71 +/- 0.64 vs. 5.27
      +/- 0.34 vs. 5.22 +/- 0.38 mm; P < 0.001), and brachial artery diameter (3.29 +/-
      0.44 vs. 3.06 +/- 0.36 vs. 2.97 +/- 0.30 mm; P = 0.006). Aortic root diameter was
      greater in TS than normal control women. TS status, height, weight, and IMT were
      independently associated with increased CD after multivariate adjustment (P <
      0.05). TS status, age, diastolic blood pressure, and CD remained independently
      associated with increased IMT after multivariate adjustment (P < 0.05). Pulse
      wave velocity and flow-mediated dilatation were similar among the three groups.
      CONCLUSION: Women with TS have greater IMT and conduit artery diameters than
      normal controls. Similarly, increased IMT in TS and 46,XX PA women suggests that
      estrogen deficiency contributes to intimal thickening. Interventional studies are
      required to determine the extent to which blood pressure and estrogen deficiency
      may be appropriate therapeutic targets to reduce cardiovascular risk in TS.

PMID- 15985481
TI  - Does a gender-related effect of growth hormone (GH) replacement exist on
      cardiovascular risk factors, cardiac morphology, and performance and
      atherosclerosis? Results of a two-year open, prospective study in young adult men
      and women with severe GH deficiency.
AB  - CONTEXT: GH secretion and response to GH replacement are gender-related.
      OBJECTIVE: The objective of this study was to investigate the effects of GH
      deficiency (GHD) and replacement on the cardiovascular system according to
      gender. DESIGN: The design was open and prospective. SETTING: The study was
      conducted at a university hospital. SUBJECTS: Subjects included 36 severe adult
      onset GHD patients (18 men, 20 women, aged < 45 yr); 36 gender-, age-, and body
      mass index-matched healthy subjects served as controls. INTERVENTIONS: Subjects
      received GH replacement at a median dose of 6.5 microg/kg.d in men and 7.7
      microg/kg.d in women for 2 yr. MAIN OUTCOME MEASURES: Homeostasis model
      assessment index, total to HDL cholesterol ratio, fibrinogen and C-reactive
      protein levels, left ventricular mass index, blood pressure, heart rate,
      diastolic filling, and systolic function at rest and at peak exercise and intima
      media thickness (IMT) at common carotid arteries were measured. RESULTS: Basal
      prevalence and/or degree of insulin resistance, lipid alterations, compromised
      cardiac function, and IMT were similar in women and men. Diastolic dysfunction
      was more prevalent in men (61 vs. 25%, P = 0.036). After GH replacement, IGF-I
      levels normalized in all patients. Lipid profile, fibrinogen, and C-reactive
      protein levels normalized in all cases. The total to HDL ratio (P = 0.04) was
      higher in women than men. The homeostasis model assessment index persisted higher
      in GHD patients than controls and decreased only in GHD men (P = 0.017). Left
      ventricular mass index normalized during treatment in both women and men,
      abnormal diastolic function persisted in three women (P = 0.031), and abnormal
      systolic performance persisted in six women and one man (P = 0.13). IMT decreased
      similarly in women and men, persisting higher than in controls. Exercise
      performance normalized in all. CONCLUSIONS: Two-year GH replacement has similar
      beneficial effects on cardiac and exercise performance and atherosclerosis in
      women and men with severe GHD.

PMID- 15985482
TI  - Obese subjects carrying the 11482G>A polymorphism at the perilipin locus are
      resistant to weight loss after dietary energy restriction.
AB  - CONTEXT: Dietary treatment of obesity could be improved if predictive information
      about the individual's genetic response to diet was available. Adipose tissue has
      been the focus of efforts to identify candidate genes. Perilipin is a major
      protein found in adipocytes, and perilipin knockout mice are lean and resistant
      to diet-induced obesity. OBJECTIVE: The objective of the study was to examine the
      association of several polymorphisms at the perilipin (PLIN) locus with obesity
      and weight reduction in response to a low-energy diet in obese patients. DESIGN:
      This study was a 1-yr randomized (depending on the PLIN genotype) trial with
      three follow-up evaluations. SETTING: The study was conducted at a university
      research center. SUBJECTS: One hundred fifty obese patients (body mass index, 42
      +/- 8 kg/m2) at baseline and 48 patients who completed the dietary follow-up
      treatment for weight loss participated in the study. INTERVENTIONS: Subjects
      completed a 1-yr low-energy diet. MAIN OUTCOMES MEASUREMENTS: Body weight (BW) at
      baseline and 3, 6, and 12 months was measured. RESULTS: The minor A-allele at the
      PLIN 11482G>A polymorphism was associated with lower baseline BW. Moreover, we
      found a gene-diet interaction (P = 0.015) between this polymorphism and weight
      loss in patients that completed the 1-yr dietary treatment. Diet resulted in
      significant decreases in BW (from 114.3 +/- 3.9 kg at baseline to 105.5 +/- 3.5
      kg at 1 yr; P lineal trend, 0.020) in GG patients (n = 33). Conversely, carriers
      of the minor A allele (n = 15) did not show significant changes in BW (from 105.0
      +/- 4.6 kg at baseline to 104.3 +/- 4.4 kg at 1 yr; P lineal trend, 0.985). This
      gene-diet interaction remained statistically significant, even after adjustment
      for differences in BW at baseline and for other potential confounders.
      CONCLUSIONS: PLIN11482A carriers were resistant to weight loss, suggesting that
      this polymorphism may predict outcome of BW reduction strategies based on low
      energy diets.

PMID- 15985483
TI  - A prospective study of the effects of radioiodine therapy for hyperthyroidism in
      patients with minimally active graves' ophthalmopathy.
AB  - CONTEXT: Radioiodine is an effective and safe treatment for hyperthyroidism but
      has been implicated as a risk factor for deterioration or new presentation of
      Graves' ophthalmopathy (GO). Prophylactic glucocorticoids appear to prevent this
      effect. OBJECTIVE: The objective of this study was to document the course of GO
      after radioiodine therapy. DESIGN: This was a prospective observational study.
      Patients were assessed at baseline and 2, 4, 6, and 12 months after radioiodine
      therapy. SETTING: The study was conducted at a tertiary referral center.
      PATIENTS: Seventy-two GO patients with minimally active eye disease participated
      in the study. INTERVENTION: A fixed dose of radioiodine was administered. T(4)
      was commenced 2 wk later to prevent hypothyroidism. MAIN OUTCOME MEASURES: Change
      in activity and severity of GO were analyzed. RESULTS: Exophthalmometer readings,
      the width of the palpebral aperture, diplopia scores, and the clinical activity
      score improved significantly. By clinically significant criteria, the eye disease
      improved in four patients (transiently in three of the four cases), most likely
      attributable to the natural course of the disease. No patient's eyes
      deteriorated. CONCLUSIONS: Radioiodine is not associated with deterioration of GO
      in patients with minimally active eye disease when postradioiodine hypothyroidism
      is prevented.

PMID- 15985484
TI  - Impact of common polymorphisms in candidate genes for insulin resistance and
      obesity on weight loss of morbidly obese subjects after laparoscopic adjustable
      gastric banding and hypocaloric diet.
AB  - CONTEXT: It is unknown whether genetic factors that play an important role in
      body weight homeostasis influence the response to laparoscopic adjustable gastric
      banding (LAGB). OBJECTIVE: We investigated the impact of common polymorphisms in
      four candidate genes for insulin resistance on weight loss after LAGB. DESIGN:
      The design was a 6-month follow-up study. SETTING: The study setting was
      hospitalized care. PATIENTS: A total of 167 unrelated morbidly obese subjects
      were recruited according to the following criteria: age, 18-66 yr inclusive; and
      body mass index greater than 40 kg/m2 or greater than 35.0 kg/m2 in the presence
      of comorbidities. INTERVENTION: LAGB was used as an intervention. MAIN OUTCOME
      MEASURE: Measure of correlation between weight loss and common polymorphisms in
      candidate genes for insulin resistance and obesity was the main outcome measure.
      RESULTS: The following single nucleotide polymorphisms were detected by digestion
      of PCR products with appropriate restriction enzymes: Gly972Arg of the insulin
      receptor substrate-1 gene, Pro12Ala of the proliferator-activated receptor-gamma
      gene, C-174G in the promoter of IL-6 gene, and G-866A in the promoter of
      uncoupling protein 2 gene. Baseline characteristics including body mass index did
      not differ between the genotypes. At the 6-month follow-up after LAGB, carriers
      of G-174G IL-6 genotype had lost more weight than G-174C or C-174C genotype (P =
      0.037), and carriers of A-866A uncoupling protein 2 genotype had lost more weight
      as compared with G-866G (P = 0.018) and G-866A (P = 0.035) genotype,
      respectively. Weight loss was lower in carriers of Gly972Arg insulin receptor
      substrate-1 genotype than Gly972Gly carriers, but not statistically significant
      (P = 0.06). No difference between carriers of Pro12Ala and Pro12Pro proliferator
      activated receptor-gamma genotype was observed. CONCLUSIONS: These data
      demonstrate that genetic factors, which play an important role in the regulation
      of body weight, may account for differences in the therapeutic response to LAGB.

PMID- 15985485
TI  - Upstream transcription factor-1 gene polymorphism is associated with increased
      adipocyte lipolysis.
AB  - OBJECTIVE: Variations in lipid metabolism between individuals could be due to
      genetic factors. A transmission of a haplotype of the upstream transcription
      factor-1 (USF-1) gene containing the minor alleles at the usf1s1 and usfs2 loci
      is described. We investigated whether these polymorphisms are associated with
      adipocyte lipolysis. METHODS AND RESULTS: A total of 196 healthy obese women were
      investigated for in vitro lipolysis regulation in sc fat cells, which was set in
      relation to the usf1s1 C-->T and usf1s2 G-->A polymorphisms in the usf1 gene. The
      two polymorphisms were in complete linkage disequilibrium. The usf1s1/2 T/A
      allele was associated with increases in the maximum lipolytic action of
      noradrenaline (P = 0.005), dobutamine (P = 0.008), terbutaline (P = 0.008),
      CGP12177 (P = 0.015), and forskolin (P = 0.006). In contrast, no significant
      genotype effect on lipolytic sensitivity (i.e. half-maximum effective
      concentration) for any of the drugs was demonstrated. Analysis of adipose tissue
      mRNA expression in 78 women from genes regulating lipolysis at the
      postadrenoceptor level showed an increased level of protein kinase A subunit
      R1alpha in the T/A genotype (P = 0.02). CONCLUSIONS: Polymorphism in the usf1
      gene is associated with increased lipolytic effect of catecholamines in fat
      cells, which is localized at the postadrenoceptor level, possibly, at least,
      involving protein kinase A.

PMID- 15985486
TI  - Circulating antiandrogenic activity in children with congenital adrenal
      hyperplasia during peroral flutamide treatment.
AB  - CONTEXT: The degree of androgen receptor blockade achieved with peroral flutamide
      is unknown. OBJECTIVE: The aim of this study was to examine the contribution of
      flutamide to circulating antiandrogenic activity in children with congenital
      adrenal hyperplasia using a recombinant cell bioassay. DESIGN: We describe an
      open-label, prospective clinical study. SETTING: The study was conducted at the
      Hospital for Children and Adolescents, University of Helsinki, or the Turku
      University Hospital, Finland. PARTICIPANTS: Seven children, age 7.2-10.5 yr, were
      included. INTERVENTION: As an experimental approach to improve control of height
      velocity and the rate of bone maturation, the patients received letrozole (2.5
      mg/d) and flutamide (10 mg/kg.d) and were followed up at 3-month intervals for 3
      12 months. Before employing the bioassay, two pools of sera (obtained before and
      during flutamide treatment) were supplemented with increasing amounts of
      testosterone, and all sera (n = 27) of individual patients were supplemented with
      a constant amount of exogenous testosterone. MAIN OUTCOME MEASURE: The main
      outcome measure was circulating antiandrogenic activity. RESULTS: Flutamide
      and/or its metabolites shifted the dose-response curve of testosterone, in that
      only the highest testosterone concentration, corresponding to 1803 ng/dl (62.5
      nm) in human serum, was measurable by the bioassay. In individual sera
      supplemented with testosterone, flutamide treatment suppressed androgen
      bioactivity from 378 +/- 20 ng/dl (13.1 +/- 0.7 nm) (mean +/- sem) (pretreatment)
      to 110 +/- 20 ng/dl (3.8 +/- 0.7 nm) (3 months), 83.7 +/- 12 ng/dl (2.9 +/- 0.4
      nm) (6 months), 46.2 +/- 6 ng/dl (1.6 +/- 0.2 nm) (9 months), and 57.7 +/- 9
      ng/dl (2.0 +/- 0.3 nm) (12 months) testosterone equivalents (P < 0.01).
      CONCLUSIONS: A dose of flutamide less than 10 mg/kg.d appears sufficient to
      inhibit AR in children. The recombinant cell bioassay employed herein offers a
      novel means to monitor the treatment of patients receiving antiandrogens.

PMID- 15985487
TI  - A common polymorphism in the CYP3A7 gene is associated with a nearly 50%
      reduction in serum dehydroepiandrosterone sulfate levels.
AB  - CONTEXT: CYP3A7, expressed in the human fetal liver and normally silenced after
      birth, plays a major role in the 16alpha-hydroxylation of dehydroepiandrosterone
      (DHEA), DHEA sulfate (DHEAS), and estrone. Due to a replacement of part of the
      CYP3A7 promoter with a sequence identical with the same region in the CYP3A4
      promoter (referred to as CYP3A7*1C), some individuals still express a variant of
      the CYP3A7 gene later in life. OBJECTIVE: The objective of this study was to
      examine the effect of the CYP3A7*1C polymorphism on serum steroid hormone levels.
      DESIGN, SETTING, PARTICIPANTS: Two population-based cohort studies were
      performed. Study group 1 consisted of 208 subjects randomly selected from the
      Rotterdam Study, and study group 2 consisted of 345 elderly independently living
      men. MAIN OUTCOME MEASURES: Serum DHEA(S), androstenedione, estradiol, estrone,
      and testosterone levels were the main outcome measures. RESULTS: In study groups
      1 and 2, heterozygous CYP3A7*1C carriers had almost 50% lower DHEAS levels
      compared with homozygous carriers of the reference allele [study group 1, 1.74 +/
      0.25 vs. 3.33 +/- 0.15 micromol/liter (P = 0.02); study group 2, 2.09 +/- 0.08
      vs. 1.08 +/- 0.12 micromol/liter (P < 0.001)]. No differences in circulating
      DHEA, androstenedione, estradiol, or testosterone levels were found. However, in
      study group 2, serum estrone levels were lower in heterozygous CYP3A7*1C carriers
      compared with homozygous carriers of the reference allele (0.11 +/- 0.002 vs.
      0.08 +/- 0.006 nmol/liter; P < 0.001). CONCLUSION: The CYP3A7*1C polymorphism
      causes the persistence of enzymatic activity of CYP3A7 during adult life,
      resulting in lower circulating DHEAS and estrone levels.

PMID- 15985488
TI  - Interactions among thyroid function, insulin sensitivity, and serum lipid
      concentrations: the Fremantle diabetes study.
AB  - CONTEXT: Recent observations in healthy subjects showed that insulin resistance
      modifies the relationship between serum cholesterol and thyroid function.
      OBJECTIVE: The aim of the study was to determine whether insulin sensitivity
      modifies the association between thyroid dysfunction and lipid parameters in
      diabetic patients. DESIGN: This is a cross-sectional study. SETTING: This is a
      community-based observational study. PATIENTS: One hundred seventeen females with
      type 2 diabetes who were not taking oral hypoglycemic therapy, insulin, or lipid
      lowering therapy participated in the study. INTERVENTION: Serum TSH, insulin,
      total and high-density lipoprotein cholesterol, and triglycerides were measured.
      MAIN OUTCOME MEASURES: Age-adjusted multiple linear regression analysis of serum
      lipid concentrations and derived parameters, as functions of serum TSH and
      homeostasis model assessment-derived insulin sensitivity (HOMA-S), were measured.
      RESULTS: The relationship among serum lipid concentrations, serum TSH, and HOMA-S
      was significantly modified by an interaction term ln(TSH)*ln(HOMA-S). In three
      dimensional graphs, there were strong positive associations between TSH and lipid
      parameters with adverse cardiac risks at low insulin sensitivity that were absent
      at higher insulin sensitivity. The effect was strongest for lipid risk factors
      associated with insulin resistance. CONCLUSIONS: The interaction between thyroid
      function and insulin sensitivity is an important contributor to diabetic
      dyslipidemia and may justify T4 replacement in some patients.

PMID- 15985489
TI  - The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader
      Willi syndrome.
AB  - CONTEXT: Narcoleptic patients with cataplexy have a general loss of hypocretin
      (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated
      degeneration of the hypocretin neurons. In addition to excessive daytime
      sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like
      symptoms, such as sleep-onset rapid eye movement sleep and cataplexy, independent
      of obesity-related sleep disturbances, which suggests a disorder of the
      hypocretin neurons. OBJECTIVE: We hypothesized that the narcolepsy-like symptoms
      in PWS are caused by a decline in the number of hypocretin neurons. DESIGN: We
      estimated the number of hypocretin neurons in postmortem hypothalami using
      immunocytochemistry and an image analysis system. SETTING: This study was
      conducted at the Netherlands Institute for Brain Research. PATIENTS: Eight PWS
      adults, three PWS infants, and 11 controls were studied. MAIN OUTCOME MEASURE:
      The total number of hypocretin neurons in the lateral hypothalamus was measured.
      RESULTS: There was no significant difference in the total number of hypocretin
      containing neurons among the seven PWS patients (in whom sufficient hypothalamic
      material was available to quantify total cell number) and seven age-matched
      controls, either in adults or in infants. A significant decline with age was
      found in adult PWS patients (r = -0.9; P = 0.037). CONCLUSIONS: We conclude that
      a decrease in the number of hypocretin neurons does not play a major role in the
      occurrence of narcolepsy-like symptoms in PWS.

PMID- 15985490
TI  - Free fatty acid-induced insulin resistance in the obese is not prevented by
      rosiglitazone treatment.
AB  - OBJECTIVE: Elevation of free fatty acids (FFAs) by the infusion of triglyceride
      heparin emulsion infusion (TG-Hep) causes insulin resistance (IR). We examined
      the effect of insulin sensitizer (rosiglitazone) on FFA-induced IR. DESIGN: Nine
      obese subjects underwent a 6-h infusion of TG-Hep before and after 6 wk of
      rosiglitazone (8 mg/d) treatment. Hyperinsulinemic euglycemic clamps were
      performed during 0-2 and 4-6 h of TG-Hep. RESULTS: After rosiglitazone for 6 wk,
      fasting FFA concentration fell, but not significantly (489 +/- 63 at 0 wk; 397 +/
      58 micromol/liter at 6 wk; P = 0.16), whereas C-reactive protein (4.26 +/- 0.95
      at 0 wk; 2.03 +/- 0.45 microg/ml at 6 wk) and serum amyloid A (17.36 +/- 4.63 at
      0 wk; 8.77 +/- 1.63 microg/ml at 6 wk) decreased significantly. At 0 wk, TG-Hep
      infusion caused a decrease in glucose infusion rate (GIR) from 4.49 +/- 0.95
      mg/kg.min to 3.02 +/- 0.59 mg/kg.min (P = 0.018). Rosiglitazone treatment
      resulted in an increase in baseline GIR to 6.29 +/- 0.81 mg/kg.min (P = 0.03 vs.
      0 wk), which decreased to 4.52 +/- 0.53 mg/kg.min (P = 0.001) after 6 h of TG-Hep
      infusion. The decrease in GIR induced by TG-Hep infusion was similar before and
      after rosiglitazone therapy [1.47 +/- 0.50 vs. 1.77 0.3 mg/kg.min (28.9 +/- 6.5
      vs. 26.4 +/- 3.7%); P = 0.51]. The rise in FFAs and triglycerides after TG-Hep
      infusion was significantly lower at 6 wk (P = 0.006 for FFAs; P = 0.024 for
      triglycerides). CONCLUSIONS: We conclude that rosiglitazone: 1) causes a
      significant increase in GIR; 2) induces a decrease in inflammatory mediators, C
      reactive protein, and serum amyloid A; 3) decreases the rise in FFAs and
      triglycerides after TG-Hep infusion; and 4) does not prevent FFA-induced IR.

PMID- 15985491
TI  - Maternal and seasonal predictors of change in calcaneal quantitative ultrasound
      during pregnancy.
AB  - BACKGROUND: During pregnancy, mineralization of the fetal skeleton and obligate
      urinary losses require adaptation of maternal calcium homeostasis, such as
      increased intestinal calcium absorption and bone resorption. However, the
      environmental determinants of maternal bone resorption during pregnancy in
      healthy adult mothers have not been previously described. SUBJECTS AND METHODS:
      We conducted a population-based longitudinal study of 307 term pregnancies using
      a cohort of 307 pregnant women living in Southampton, United Kingdom. During
      early and late pregnancy, skeletal status was measured at the left calcaneus
      using quantitative ultrasound (QUS). RESULTS: There was a significant (P < 0.001)
      decline in both speed of sound and broadband ultrasound attenuation during
      pregnancy. Those women who were pregnant for the first time (P = 0.001), had low
      milk intake prepregnancy (P = 0.01), and reduced measures of fat mass (P = 0.01)
      showed the greatest decline in calcaneal bone measurements. Furthermore, those
      women who were pregnant over winter months had greater losses in calcaneal QUS (P
      = 0.02). CONCLUSION: Maternal lifestyle, fat stores, and seasonality of early
      pregnancy influence maternal calcaneal QUS loss during pregnancy; the findings
      support a role for vitamin D supplementation of women pregnant during winter,
      especially those with low calcium intakes who are pregnant for the first time.

PMID- 15985492
TI  - Predictors of endothelial dysfunction in young women with polycystic ovary
      syndrome.
AB  - CONTEXT: Women with polycystic ovary syndrome (PCOS) may be at increased risk for
      cardiovascular disease. Endothelial dysfunction is an early marker of
      atherosclerosis. OBJECTIVES: The objectives of this study were to 1) compare
      endothelial function in young women with PCOS and regularly menstruating control
      women, and 2) to identify the determinants of endothelial function and
      investigate its relationship with body mass index in women with PCOS. DESIGN:
      This was a cross-sectional study. SETTING: This study was conducted at a tertiary
      cardiovascular research center. PATIENTS: Sixty-two young women with PCOS (mean
      age, 22.7 yr) and 17 control women, matched as a group for age and body mass
      index, were studied. Twenty-three women with PCOS were lean, 21 were overweight,
      and 18 were obese. MAIN OUTCOME MEASURES: Endothelium-dependent and -independent
      vascular function was assessed by measuring flow-mediated dilation (FMD) and
      nitrate-mediated dilation in the brachial artery (diameter change during hand
      hyperemia and after sublingual glyceryl trinitrate administration, respectively).
      RESULTS: FMD and nitrate-mediated dilation were significantly lower in PCOS than
      in control women (reduced by approximately 50 and 25%, respectively; both P <
      0.0005). Insulin resistance, total testosterone, and total cholesterol were
      independent predictors of FMD, accounting for 21, 10, and 9% of the variance,
      respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to
      overweight and obese PCOS women was observed, but differences among groups were
      not statistically significant. CONCLUSIONS: Women with PCOS have significant
      endothelial dysfunction at an early age (i.e. early 20s), and largely independent
      of obesity. This suggests that women with PCOS are at increased risk for early
      onset cardiovascular disease and may gain particular benefit from measures to
      improve endothelial function.

PMID- 15985493
TI  - A novel EXT1 splice site mutation in a kindred with hereditary multiple exostosis
      and osteoporosis.
AB  - CONTEXT: Hereditary multiple exostosis (HME) is an autosomal dominant disorder
      characterized by the development of benign cartilage-capped tumors at the juxta
      epiphyseal regions of long bones. HME is usually caused by mutations of EXT1 or
      EXT2. OBJECTIVE: The objective of this study was to investigate a three
      generation Austrian kindred with HME for EXT1 and EXT2 mutations and for
      abnormalities of bone mineral density (BMD). METHODS: DNA sequence and mRNA
      analyses were used to identify the mutation and its associated consequences.
      Serum biochemical and radiological investigations assessed bone metabolism and
      BMD. RESULTS: HME-affected members had a lower femoral neck BMD compared with
      nonaffected members (z-scores, -2.98 vs. -1.30; P = 0.011), and in those less
      than 30 yr of age, the lumbar spine BMD was also low (z-scores, -2.68 vs. -1.42;
      P = 0.005). However, they had normal mobility and normal serum concentrations of
      calcium, phosphate, alkaline phosphatase activity, creatinine, PTH, 25
      hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, and beta-crosslaps. DNA
      sequence analysis of EXT1 revealed a heterozygous g-->c transversion that altered
      the invariant ag dinucleotide of the intron 8 acceptor splice site. RT-PCR
      analysis using lymphoblastoid RNA showed that the mutation resulted in skipping
      of exon 9 with a premature termination at codon 599. DNA sequence abnormalities
      of the osteoprotegerin gene, which is in close proximity to the EXT1 gene, were
      not detected. CONCLUSIONS: A novel heterozygous acceptor splice site mutation of
      EXT1 results in HME that is associated with a low peak bone mass, indicating a
      possible additional role for EXT1 in bone biology and in regulating BMD.

PMID- 15985494
TI  - Comparison of bladder cancer mortality in five countries: France, Italy, Japan,
      UK and USA from the WHO Mortality Database (1960-2000).

PMID- 15985495
TI  - PhD: a web database application for phenotype data management.
AB  - A database application has been developed for phenotype data management employing
      the Entity-Attribute-Value (EAV) model. By applying the EAV model, this
      application allows users to manage arbitrary phenotypes and customize data entry
      forms; therefore, it is suitable for different and multi-center projects.

PMID- 15985496
TI  - Alignment of metabolic pathways.
AB  - MOTIVATION: Several genome-scale efforts are underway to reconstruct metabolic
      networks for a variety of organisms. As the resulting data accumulates, the need
      for analysis tools increases. A notable requirement is a pathway alignment finder
      that enables both the detection of conserved metabolic pathways among different
      species as well as divergent metabolic pathways within a species. When comparing
      two pathways, the tool should be powerful enough to take into account both the
      pathway topology as well as the nodes' labels (e.g. the enzymes they denote), and
      allow flexibility by matching similar--rather than identical--pathways. RESULTS:
      MetaPathwayHunter is a pathway alignment tool that, given a query pathway and a
      collection of pathways, finds and reports all approximate occurrences of the
      query in the collection, ranked by similarity and statistical significance. It is
      based on a novel, efficient graph matching algorithm that extends the
      functionality of known techniques. The program also supports a visualization
      interface with which the alignment of two homologous pathways can be graphically
      displayed. We employed this tool to study the similarities and differences in the
      metabolic networks of the bacterium Escherichia coli and the yeast Saccharomyces
      cerevisiae, as represented in highly curated databases. We reaffirmed that most
      known metabolic pathways common to both the species are conserved. Furthermore,
      we discovered a few intriguing relationships between pathways that provide
      insight into the evolution of metabolic pathways. We conclude with a description
      of biologically meaningful meta-queries, demonstrating the power and flexibility
      of our new tool in the analysis of metabolic pathways.

PMID- 15985497
TI  - Determination of 234U/238U ratio: comparison of multi-collector ICPMS and ICP-QMS
      for water, hair and nails samples, and comparison with alpha-spectrometry for
      water samples.
AB  - The (234)U/(238)U ratio in water, hair and nails samples was determined by multi
      collector inductively coupled plasma mass spectrometry (MC-ICPMS) and inductively
      coupled plasma quadrupole mass spectrometry (ICP-QMS) and by alpha-spectrometry
      for the water samples only. A correlation of 0.99 was found between the two ICPMS
      methods and of 0.98 with alpha-spectrometry. The range of activity ratios was
      between 0.9 and 2.6 according to the MC-ICPMS measurements. The reproducibility
      of both ICPMS techniques was better than 4% for water samples containing 1 mug l(
      1) of uranium and a (234)U/(238)U atom ratio of 54.9 x 10(-6). Sample preparation
      for the ICPMS consisted of dilution of water samples containing >10 microg l(-1)
      of uranium and measurement time was approximately 1 min, while alpha-spectrometry
      involved pre-concentration and separation of the uranium and counting times of
      1,000 min.

PMID- 15985498
TI  - Variations observed in environmental radiation at ground level.
AB  - To investigate and monitor environmental radiation at ground level, Physikalisch
      Technische Bundesanstalt (PTB) has installed several dosemeters and particle
      detectors at the new Ambient Radiation Dosimetry Site. The separation of the
      total ambient dose equivalent rate H*10(env) of environmental radiation into the
      different contributions is achieved by comparing the data of different detectors:
      the muon detector MUDOS, a modified neutron dosemeter, proportional counters and
      ionisation chambers. The response of the latter two dosemeter systems to cosmic
      radiation was determined at the Cosmic Radiation Dosimetry Site on a lake near
      PTB. Besides the increase of the ambient dose equivalent rate during rainfall,
      variations owing to air pressure, solar activity and temperature changes in the
      upper atmosphere are observed. Without rain and solar effects, smooth variations
      of the cosmic component at ground level of +/-6.9 nSv h(-1) should be treated as
      naturally occurring variations during an entire year.

PMID- 15985499
TI  - Quantitative analysis of gamma-ray emitters radioisotopes in commercialised
      bottled water in Tunisia.
AB  - A set of measurements have been conducted in order to determine the annual
      effective dose resulting from the ingestion of natural radionuclides present in
      eight different brands of bottled water commercialised in Tunisia. Using high
      resolution gamma spectrometry technique, we have noted the presence of the
      following radionuclides: 214Bi, 226Ra, 228Ac, 212Pb, 235U and 40K. For all
      classes of age, only the radium concentration was found to be significant in the
      calculation of the equivalent dose. Some of the studied samples exceeded the
      reference level of 0.1 mSv y(-1) of effective dose.

PMID- 15985500
TI  - Preliminary study of using imaging plates to map skin dose of patients in
      interventional radiology procedures.
AB  - A method using europium-doped BaFBr imaging plates (IPs) has been studied for
      mapping entrance skin doses during interventional radiology (IR); the mapping is
      useful for detecting overlap between irradiation fields and determining the most
      exposed skin areas. IPs, which are two-dimensional radiation sensors made of
      photostimulated luminescence materials, have a linear dose response up to
      approximately 100 Gy, can accurately measure doses from 1 microGy to 10 Gy and
      can be used repeatedly. Because the energy dependence of IPs is rather high, the
      IPs were characterised in this study and a sensitivity variation of approximately
      13% was observed for effective energies of 32.7 to 44.7 keV, which are used in IR
      procedures. Simulation of actual interventional cardiology procedures showed that
      the variation of sensitivity was within 5%, meaning that IPs are practical for
      measuring skin doses during IR. Moreover, the patient data can be stored online
      and easily called up when IR procedures must be repeated, helping to prevent
      radiation injuries.

PMID- 15985501
TI  - Determinants of anemia in pre-school children in the occupied Palestinian
      territory.
AB  - This paper presents the main findings of an analysis linking the dependent
      variable - anemia in pre-school children - to its determinants, to identify
      priority groups for action. The study was a cross sectional survey of randomly
      selected pre-school children 6-59 months (n = 3331) in the occupied Palestinian
      territory during the current uprising. Anemia (Hb <11 g/dl) in children was
      determined by a blood sample. Other indicators were examined; 24 variables
      related to the family, housing, maternal and child characteristics, in addition
      to changes in income and food intake that occurred during the uprising.
      Multivariate analysis revealed that anemia was independently related to reduction
      in income, iron intake, infrequent gastrointestinal infections, stunting and
      current breast feeding status. In addition, region was an independent risk factor
      for anemia - in the West Bank there were fewer anemic children in the age group 6
      35 months compared to children from the same age group living in the Gaza Strip.

PMID- 15985502
TI  - Comparison of axillary, rectal and tympanic temperature measurements in children
      admitted with malaria.
AB  - We compared axillary, rectal and tympanic temperatures in children admitted with
      severe malaria. The axillary temperatures were 0.74 degrees C (95% limits of
      agreement -0.85 to 2.33 degrees C) less than rectal temperatures and tympanic
      temperatures 0.42 degrees C (95% limits of agreement -0.16 to 2.44 degrees C)
      less than rectal temperatures. The difference was greater on admission than 24
      hours later. These differences may be important in defining criteria for clinical
      syndromes.

PMID- 15985503
TI  - Seeing through the mist: abundance versus percentage. Commentary on metabolites
      in safety testing.
AB  - Recent attention has been given to the potential roles that metabolites could
      play in safety evaluations of new drugs. In 2002, a proposal was published on
      "metabolites in safety testing" ("MIST"), which suggested some guidelines
      regarding when it is necessary to provide greater assessment of the safety of
      metabolites. However, this proposal was based on relative abundance values, i.e.,
      the percentage that a metabolite comprises of total exposure to drug-related
      material. In the present commentary, we propose that absolute abundance criteria
      be used rather than relative abundance. The absolute abundance of a metabolite in
      circulation or excreta in humans should be combined with other information
      regarding the chemical structure of the metabolite (e.g., similarity to the
      parent drug, presence of chemically reactive substituents) and potential
      mechanisms of toxicity (e.g., suprapharmacological effects, secondary
      pharmacological effects, nonspecific effects). Decision trees are described that
      can be used to address human metabolites in safety testing.

PMID- 15985504
TI  - Patient satisfaction with health care providers in South Africa: the influences
      of race and socioeconomic status.
AB  - OBJECTIVE: The first democratic government elected in South Africa in 1994
      inherited huge inequalities in health status and health provision across all
      sections of the population. This study set out to assess, 4 years later, the
      influence of race and socioeconomic status (SES) on perceived quality of care
      from health care providers. DESIGN: A 1998 countrywide survey of 3820 households
      assessed many aspects of health care delivery, including levels of satisfaction
      with health care providers among different segments of South African society.
      RESULTS: Fifty-one percent (n = 1953) of the respondents had attended a primary
      care facility in the year preceding the interview and were retained in the
      analysis. Both race and SES were significant predictors of levels of satisfaction
      with the services of the health care provider, after adjusting for gender, age,
      and type of facility visited. White and high SES respondents were about 1.5 times
      more likely to report excellent service compared with Black and low SES
      respondents, respectively. CONCLUSION: In South Africa, race and SES are not
      synonymous and can no longer be considered reliable proxy indicators of one
      another. Each has distinct and significant but different degrees of association
      with client satisfaction. Any assessment of equity-driven health policy in South
      Africa should consider the impacts of both race and SES on client satisfaction as
      one of the indicators of success.

PMID- 15985505
TI  - Evaluating claims-based indicators of the intensity of end-of-life cancer care.
AB  - OBJECTIVE: To evaluate measures that could use existing administrative data to
      assess the intensity of end-of-life cancer care. METHODS: Benchmarking standards
      and statistical variation were evaluated using Medicare claims of 48,906 patients
      who died from cancer from 1991 through 1996 in 11 regions of the United States.
      We assessed accuracy by comparing administrative data to 150 medical records in
      one hospital and affiliated cancer treatment center. RESULTS: Systems not
      providing overly aggressive care near the end of life would be ones in which less
      than 10% of patients receive chemotherapy in the last 14 days of life, less than
      2% start a new chemotherapy regimen in the last 30 days of life, less than 4%
      have multiple hospitalizations or emergency room visits or are admitted to the
      intensive care unit (ICU) in the last month of life, and less than 17% die in an
      acute care institution. At least 55% of patients would receive hospice services
      before death from cancer, and less than 8% of those would be admitted to hospice
      within only 3 days of death. All measures were found to have accuracy ranging
      from 85 to 97% and 2- to 5-fold adjusted variability between the 5th and 95th
      percentiles of performance. CONCLUSIONS: The usefulness of these measures will
      depend on whether the concept of intensity of care near death can be further
      validated as an acceptable and important quality issue among patients, their
      families, health care providers, and other stakeholders in oncology.

PMID- 15985506
TI  - The effect of changing reimbursement policies on quality of in-patient care, from
      fee-for-service to prospective payment.
AB  - OBJECTIVE: Using insurance claims for hemorrhoidectomies, we examined the effect
      of Taiwan's Bureau of National Health Insurance's case payment system, a fixed
      case payment rate method used to reimburse health care providers for in-patient
      care. DESIGN: This observational natural experimental study examined changes in
      medical care that occurred between two phases: the 9 months before case payment
      system was implemented on 1 October 1997 and the 9 months afterwards. The changes
      were analyzed by performing linear regressions with interaction between hospital
      type and the implementation of case payment system. SETTING: This study was based
      on total claim data from National Health Insurance. STUDY PARTICIPANTS: A total
      of 23 638 hemorrhoidectomy insurance claims. MAIN OUTCOME MEASURES: Length of
      stay, number of medical services, and number of drug prescriptions. Medical
      services were stratified into those that were considered minimal requirements and
      those considered optional by the Bureau of National Health Insurance. RESULTS:
      Over the 18-month period, the number of patients increased by 23.7%. After the
      case payment system was implemented, length of stay decreased by 0.59 days (P <
      0.0001), the number of minimally required services increased by 2.19 to 4.24
      items (P < 0.0001), the number of optional service items decreased by 0.32 items
      (P < 0.0001), and drug prescription decreased slightly by 0.58 to 0.99 items (P <
      0.0001) per hospitalization. CONCLUSIONS: The case payment system successfully
      shortened length of stay without significantly sacrificing the provision of
      services.

PMID- 15985507
TI  - Successful management of extreme hypernatraemia by haemofiltration in a patient
      with severe metabolic acidosis and renal failure.

PMID- 15985508
TI  - Long-term results in renal transplant patients with allograft dysfunction after
      switching from calcineurin inhibitors to sirolimus.
AB  - BACKGROUND: Switching from calcineurin inhibitors (CNIs) to sirolimus might
      improve renal function in chronic renal transplant patients. METHODS: In a
      prospective study, we assessed long-term efficacy and safety parameters in 43
      renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and
      tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n = 38)
      or recurrent cutaneous cancers (n = 5). A kidney biopsy was done in 79% of
      patients prior to conversion, and showed either chronic allograft nephropathy (n
      = 26) or CNI nephrotoxicity (n = 7). Conversion was either abrupt or progressive,
      with CNI withdrawal over 3 weeks. All patients also received steroids with or
      without mycophenolate mofetil or azathioprin. Patient data were recorded at
      baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post
      conversion. RESULTS: After a mean post-conversion follow-up of 27+/-1.5 months,
      58% of the patients were still on sirolimus. The survival of intent to treat
      patients and grafts was 95.3 and 93%, respectively. Overall, there was
      significant improvement in renal function, creatinine clearance increasing from
      49.4+/-14.9 to 53+/-16.3 ml/min at D30 (P = 0.01), and to 54.7+/-20 ml/min at
      D180 (P = 0.01). Thereafter, creatinine clearance was not different from
      baseline, i.e. 54.7+/-21.7, 52.8+/-20 and 51.7+/-20.3 ml/min at years 1, 1.5 and
      2, respectively. We divided the patients into two groups: responders (n = 29),
      those with an increase in creatinine clearance at 6 months post-conversion
      compared with D0, and non-responders (n = 14), those with a decrease in
      creatinine clearance at 6 months post-conversion compared with D0. In univariate
      analysis, factors predictive of response included proteinuria at D0 and the
      magnitudes of the differences between D30 and D0 for serum creatinine and lactate
      dehydrogenase. The conversion was associated with (i) significant decreases in
      serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii)
      significant increases in serum alkaline phosphatase, total cholesterol,
      parathyroid hormone, and the number of patients on statin and recombinant
      erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1
      g/day in 28% of patients (P < 0.0009), which was >2 g/day in 12% of the entire
      cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same
      Banff scores as observed at baseline. We identified three independent predictive
      factors for a renal response to the switch: absence of proteinuria, presence of
      antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30.
      CONCLUSION: Conversion from CNIs to sirolimus in renal transplant patients with
      chronic allograft nephropathy was associated with improved renal function;
      however, 33% of the patients developed overt proteinuria.

PMID- 15985509
TI  - Acupuncture in haemodialysis patients at the Quchi (LI11) acupoint for refractory
      uraemic pruritus.
AB  - BACKGROUND: Uraemic pruritus is a common problem in end-stage renal failure
      patients. Traditional therapies produce marginal or no results. Acupuncture has
      been reported to be effective. The aim of this randomized, controlled study was
      to validate a single acupoint for relieving uraemic pruritus. METHODS: We
      randomized 40 patients with refractory uraemic pruritus into two groups. In group
      1 (n = 20), acupuncture was applied unilaterally at the Quchi (LI11) acupoint
      thrice weekly for 1 month. In group 2 (controls, n = 20), acupuncture was applied
      at a non-acupoint 2 cm lateral to Quchi (LI11) thrice weekly for 1 month.
      Subjects responded to a pruritus score questionnaire given before and at the end
      of the 1 month treatment and at a 3 months follow-up. The results of the pruritus
      scores were analysed with the repeated measures general linear model to examine
      the effect of acupuncture on pruritus scores. RESULTS: In group 1, pruritus
      scores before and after acupuncture and at the 3 month follow-up were 38.3+/-4.3,
      17.3+/-5.5 and 16.5+/-4.9, and in group 2 (controls) they were 38.3+/-4.3, 37.5+/
      3.2 and 37.1+/-5, respectively. Laboratory tests showed no significant
      differences between the two groups. Pruritus scores were significantly lower
      after acupuncture and at the 3 month follow-up, P<0.001. CONCLUSIONS: Acupuncture
      at the Quchi (LI11) acupoint is an easy, safe and effective means of relieving
      uraemic pruritus.

PMID- 15985510
TI  - Relapse of lupus nephritis more than 10 years after complete remission.

PMID- 15985511
TI  - Massive post-obstructive diuresis in a patient with Burkitt's lymphoma.

PMID- 15985512
TI  - Recurrent rhabdomyolysis and myoglobinuric acute renal failure in a patient with
      polymyositis.

PMID- 15985513
TI  - Vascular access in a hemiplegic deformed arm.

PMID- 15985514
TI  - Impairment of skin microvascular reactivity in hypertension and uraemia.
AB  - BACKGROUND: Uraemia and hypertension are associated with higher risk for
      cardiovascular complications. Endothelial dysfunction plays an important role in
      the pathogenesis of cardiovascular diseases. The aim of the present study was to
      evaluate endothelial function in the forearm skin microcirculation of patients
      with essential hypertension, in hypertensive haemodialysis patients and in
      normotensive control subjects. METHODS: We performed laser Doppler flowmetry with
      iontophoresis of acetylcholine (ACh) and of sodium nitroprusside (SNP) as well as
      the post-occlusive reactive hyperaemia test (PORH) in 16 normal control subjects
      (CONT), in 16 patients with essential hypertension (EHT) and in 16 haemodialysis
      patients with essential hypertension (DHT). Plasma levels of endothelin-1, big
      endothelin and von Willebrand factor (vWF) were also measured. RESULTS: The
      average hyperaemic response to the higher dose of ACh iontophoresis was 801+/
      110% in CONT, 563+/-69 % in EHT and 308+/-64% in DHT (P<0.05, between all
      comparisons). Vasodilation to the higher dose of SNP was 791+/-79% in CONT, 633+/
      72% in EHT and 355+/-69% in DHT (NS, P<0.001 compared with controls,
      respectively). The average peak flow during PORH was significantly lower in both
      the EHT and DHT groups compared with controls (294+/-39, 267+/-59 and 429+/-45%,
      respectively, P<0.05). Levels of endothelin-1, big endothelin, vWF and vWF
      activity were significantly higher in the DHT group (P<0.05, compared with
      controls). CONCLUSIONS: In hypertensive haemodialysis patients, both endothelium
      dependent and -independent vasodilation was impaired. The observed increase in
      plasma markers of endothelial damage indicated a progression of vascular disease.

PMID- 15985515
TI  - Ultrasound imaging findings of femoral veins in patients with renal failure and
      its impact on vascular access.
AB  - BACKGROUND: Patients requiring dialysis due to acute or chronic renal failure
      frequently require temporary vascular access. Femoral vein catheterization is the
      easiest method for obtaining temporary vascular access in haemodialysis patients.
      The aim of this study was to utilize ultrasound imaging to describe femoral vein
      structures and to examine anatomical variations in uraemic patients. METHODS: We
      evaluated 114 (70 males, 44 females) renal failure patients. Femoral arteries
      were localized manually inferior to the femoral ligament, and ultrasonographic
      examination was performed from this location. Images of the vessels and
      demographic data of patients were recorded and analysed. Femoral veins were
      classified according to their diameter, patency and palpation status of the
      neighbouring femoral artery. RESULTS: Three patients had a history of prior
      femoral catheterization. In one of these, who had a history of bilateral
      catheterization, we detected bilateral femoral vein thrombosis. Overall, non
      palpable femoral arteries or unsuitable femoral veins were found unilaterally in
      16 patients (14.0%) and bilaterally in six patients (5.2%). The depth of femoral
      arteries (r = 0.54, P<0.001) and femoral veins (r = 0.59, P<0.001) was correlated
      with body mass index (BMI). Femoral arteries and femoral veins were located
      significantly deeper in overweight (BMI >25) patients compared with normal weight
      patients (20.7+/-6.5 vs 14.6+/-5.1 mm, P<0.001 and 26.1+/-6.7 vs 18.9+/-5.5 mm,
      P<0.001). CONCLUSIONS: Bilateral anatomical variations of femoral veins were
      relatively rare. However, ultrasound surveys should be performed in obese
      patients or when the femoral artery is not palpable.

PMID- 15985516
TI  - Extended epoetin alfa dosing in chronic kidney disease patients: a retrospective
      review.
AB  - BACKGROUND: The effectiveness of extended dosing of epoetin alfa beyond once
      weekly (QW) has not been well explored in patients being treated for anaemia of
      chronic kidney disease (CKD). The current study was undertaken to assess the
      effectiveness of extended dosing in maintaining haemoglobin (Hb) levels in this
      population. METHODS: A retrospective chart review was conducted to assess the
      efficacy of extended epoetin alfa dosing in patients being treated for CKD
      related anaemia. Eligible patients were to have received epoetin alfa once every
      2 weeks (Q2W), 3 weeks (Q3W), 4 weeks (Q4W), or >Q4W administered subcutaneously
      for at least 3 months to maintain Hb > or = 11.0 g/dl. Patients were > or =18
      years with serum creatinine 1.5 to 6.0 mg/dl for females and 2.0 to 6.0 mg/dl for
      males, and were not receiving renal replacement therapy. Epoetin alfa dose and
      dosing frequency were adjusted during treatment at the clinician's discretion.
      For analysis, patients were stratified into dosing groups based on their most
      dominant dosing regimen. RESULTS: 243 patients (mean age, 71.5 years; 79% white,
      54% female) who received extended epoetin alfa dosing for a mean of 10.3 months
      were eligible for analysis. Mean baseline estimated glomerular filtration rate
      and mean serum creatinine were 21.2 ml/min/1.73 m(2) and 3.1 mg/dl, respectively.
      Primary causes of CKD included hypertension (36%) and diabetes (28%). Most
      patients (82%) receiving an extended epoetin alfa regimen maintained Hb > or
      =11.0 g/dl. The most common dosing regimen was Q2W (51%). Mean Hb for each dosing
      group was maintained between 11.6 g/dl and 12.4 g/dl during the study, and
      glomerular filtration rate remained stable. Epoetin alfa was well tolerated
      across all groups. CONCLUSIONS: Data from private community nephrology practices
      showed that extended epoetin alfa dosing effectively maintained Hb > or =11.0
      g/dl in 82% of these selected patients being treated for anaemia of CKD.

PMID- 15985517
TI  - Nutcracker phenomenon or nutcracker syndrome?

PMID- 15985518
TI  - Severe syncope and sudden death in children with inborn salt-losing hypokalaemic
      tubulopathies.
AB  - BACKGROUND: Potassium deficiency may cause cardiac arrhythmias culminating in
      syncope or sudden death. METHODS: An inquiry performed among physicians caring
      for a total of 249 patients with inborn salt-losing tubulopathies revealed that
      acute cardiac complications occurred in seven children. RESULTS: Four patients
      died suddenly and three had severe syncope. These episodes occurred in the
      context of severe chronic hypokalaemia (< or =2.5 mmol/l) or were precipitated by
      acute diseases, which exacerbated hypokalaemia (< or =2.0 mmol/l). CONCLUSIONS:
      In conclusion, severe chronic or acute hypokalaemia is hazardous in inborn salt
      losing tubulopathies.

PMID- 15985519
TI  - Molecular basis for the dialysis disequilibrium syndrome: altered aquaporin and
      urea transporter expression in the brain.
AB  - BACKGROUND: Cerebral disorders caused by brain oedema characterize the dialysis
      disequilibrium syndrome, a complication of rapid haemodialysis. Brain oedema is
      presumably caused by the 'reverse urea effect', i.e. the significant urea
      gradient between blood and brain after dialysis, with, as a result, an inflow of
      water into the brain. To assess the molecular basis of this effect, we examined
      the expression of urea transporter UT-B1 and aquaporin (AQP) 4 and AQP9 in the
      brain of uraemic rats. METHODS: Brain, kidneys and one testis were collected from
      four sham-operated (control) and four uraemic rats, 10 weeks after 5/6
      nephrectomy (Nx). Protein abundance was measured by semi-quantitave
      immunoblotting using affinity-purified rabbit anti-rat antibodies applied on
      tissue crude homogenates. RESULTS: The results are expressed as means+/-SE of
      band density (arbitrary units). In Nx compared with control rats, the brain
      expression of UT-B1 was reduced by half (32+/-3 vs 62+/-8, P<0.01) whereas that
      of AQ4 was doubled (251+/-13 vs 135+/-5, P<0.001), and that of AQP9 increased by
      65% (253+/-22 vs 154+/-10, P<0.01). UT-B1 expression was also lowered by Nx in
      kidney medulla (45+/-21 vs 141+/-4, P<0.01) but was unchanged in testis.
      CONCLUSIONS: The conjunction of a reduced expression of UT-B and an increased
      expression of AQPs in brain cells may bring a new clue to understanding the DDS
      mechanism. Because of low UT-B abundance, urea exit from astrocytes is most
      probably delayed during rapid removal of extracellular urea through fast
      dialysis. This creates an osmotic driving force that promotes water entry into
      the cells (favoured by abundant AQPs) and subsequent brain swelling.

PMID- 15985520
TI  - Downregulation of parathyroid hormone receptor gene expression and osteoblastic
      dysfunction associated with skeletal resistance to parathyroid hormone in a rat
      model of renal failure with low turnover bone.
AB  - BACKGROUND: Adynamic bone disease (ABD), which is characterized by reduced bone
      formation and resorption, has become an increasingly common manifestation of bone
      abnormalities in patients with end-stage renal failure. It has been recognized
      that skeletal resistance to parathyroid hormone (PTH) underlies the pathogenesis
      of ABD; however, the mechanisms of such resistance remain unclear. METHODS: We
      established a rat model simulating ABD under chronic renal failure conditions by
      thyroparathyroidectomy and partial nephrectomy (TPTx-Nx). TPTx-Nx rats were
      infused subcutaneously with a physiological dose of PTH. We analysed bone
      histomorphometric parameters and demonstrated gene expression using semi
      quantitative reverse transcription-polymerase chain reaction. RESULTS: Reduced
      bone formation was observed in this model, simulating ABD. The reduction was
      dependent on the degree of renal dysfunction. Bone formation rate was 6.4+/-2.7
      microm3/m2/year in TPTx-5/6Nx rats and 22.7+/-7.2 microm3/m2/year in TPTx rats
      (P<0.05). Osteoblast surface was also significantly depressed (P<0.05) in TPTx
      5/6Nx (3.8+/-2.7%) compared with TPTx rats (15.9+/-8.6). The expression of
      PTH/parathyroid hormone-related peptide (PTHrP) receptor and alkaline phosphatase
      genes was reduced significantly in TPTx-Nx compared with TPTx rats (P<0.05).
      Reduced bone formation in TPTx-Nx rats was ameliorated by intermittent injection
      of pharmacological doses of PTH. CONCLUSIONS: Renal dysfunction without secondary
      hyperparathyroidism induces osteoblast dysfunction and reduces bone formation.
      Skeletal resistance to PTH develops in renal failure even at low or normal PTH
      levels, possibly through downregulation of PTH/PTHrP receptor and dysfunction of
      osteoblasts.

PMID- 15985521
TI  - Comparison of the educational deficiencies of delinquent and nondelinquent
      students.
AB  - This article assesses the differences in educational deficiencies between a
      statewide sample of delinquent students and a matched sample of nondelinquent
      students. Employing a research design that controls for a series of relevant
      individual and school variables, the study's findings document that delinquent
      students are characterized by a series of disproportionate educational
      deficiencies as compared to their nondelinquent student counterparts. Delinquent
      students were found to attain lower grade point averages, have poorer school
      attendance records, be retained more often in the same grade, and receive more
      school disciplinary actions. The article concludes that these documented
      educational deficiencies may play an integral role in the process of delinquency
      and, therefore, pose a number of public policy implications in relation to the
      prevention and treatment of delinquency.

PMID- 15985522
TI  - Major factors influencing HIV/AIDS project evaluation.
AB  - This article aimed at finding out if participatory processes (group discussions,
      enactments, and others) do make a valuable contribution in communication-based
      project implementation/evaluation and the fight against HIV/AIDS. A case study
      backed by documentary analysis of evaluation reports and occasional insights from
      interviews stood as the main methods. To identify values, the state of
      beneficiaries prior to and after project implementation/evaluation was compared.
      Participatory processes were noted to have created an enabling environment for
      project beneficiaries to become activists for social change, leading to the
      limiting of the spread of HIV/AIDS through sexual behavior and a change of
      attitude--the essence required for successful intervention. Group participatory
      processes were also noted to have contributed in overriding, to a great extent,
      limitations arising from sociodemographic differences in the attainment of
      project objectives and limitations arising from differences in forms of
      evaluation (internal versus external evaluators).

PMID- 15985523
TI  - Scaling up HIV voluntary counseling and testing in Africa: what can evaluation
      studies tell us about potential prevention impacts?
AB  - Although there is a widespread belief that scaling up HIV voluntary counseling
      and testing (VCT) programs in Africa will have large prevention benefits through
      reductions in risk behaviors, these claims are difficult to establish from
      existing evaluations of VCT. Considerations from behavioral models and the
      available data suggest that as VCT coverage expands, marginal program effects are
      likely to decline owing to changes in the degree of client selectivity, and that
      potential uptake among those at highest risk is uncertain. The article also
      assesses two other common perceptions about VCT in Africa: that a policy of
      promoting couples-oriented VCT would be more successful than one emphasizing
      individual testing and that VCT demand and prevention impacts will be enhanced
      where scaling up is accompanied by the provision of antiretroviral drugs.

PMID- 15985524
TI  - Developing a practical forecasting screener for domestic violence incidents.
AB  - In this article, the authors report on the development of a short screening tool
      that deputies in the Los Angeles Sheriff's Department could use in the field to
      help forecast domestic violence incidents in particular households. The data come
      from more than 500 households to which sheriff's deputies were dispatched in fall
      2003. Information on potential predictors was collected at the scene. Outcomes
      were measured during a 3-month follow-up. Data were analyzed with modern data
      mining procedures in which true forecasts were evaluated. A screening instrument
      was developed based on a small fraction of the information collected. Making the
      screening instrument more complicated did not improve forecasting skill. Taking
      the relative costs of false positives and false negatives into account, the
      instrument correctly forecasted future calls for service about 60% of the time.
      Future calls involving domestic violence misdemeanors and felonies were correctly
      forecast about 50% of the time. The 50% figure is important because such calls
      require a law enforcement response and yet are a relatively small fraction of all
      domestic violence calls for service.

PMID- 15985525
TI  - Analysis of global mRNA expression in human skeletal muscle during recovery from
      endurance exercise.
AB  - To search for novel transcriptional pathways that are activated in skeletal
      muscle after endurance exercise, we used cDNA microarrays to measure global mRNA
      expression after an exhaustive bout of high-intensity cycling (approximately 75
      min). Healthy, young, sedentary males performed the cycling bout, and skeletal
      muscle biopsies were taken from the vastus lateralis before, and at 3 and 48 h
      after exercise. We examined mRNA expression in individual muscle samples from
      four subjects using cDNA microarrays, used repeated-measures significance
      analysis of microarray (SAM) to determine statistically significant expression
      changes, and confirmed selected results using real-time RT-PCR. In total, the
      expression of 118 genes significantly increased 3 h postcycling and 8 decreased.
      At 48 h, the expression of 29 genes significantly increased and 5 decreased. Many
      of these are potentially important novel genes involved in exercise recovery and
      adaptation, including several involved in 1) metabolism and mitochondrial
      biogenesis (FOXO1, PPARdelta, PPARgamma, nuclear receptor binding protein 2, IL-6
      receptor, ribosomal protein L2, aminolevulinate delta-synthase 2); 2) the oxidant
      stress response (metalothioneins 1B, 1F, 1G, 1H, 1L, 2A, 3, interferon regulatory
      factor 1); and 3) electrolyte transport across membranes [Na+-K+-ATPase (beta3),
      SERCA3, chloride channel 4]. Others include genes involved in cell stress,
      proteolysis, apoptosis, growth, differentiation, and transcriptional activation,
      as well as all three nuclear receptor subfamily 4A family members (Nur77, Nurr1,
      and Nor1). This study is the first to characterize global mRNA expression during
      recovery from endurance exercise, and the results provide potential insight into
      1) the transcriptional contributions to homeostatic recovery in human skeletal
      muscle after endurance exercise, and 2) the transcriptional contributions from a
      single bout of endurance exercise to the adaptive processes that occur after a
      period of endurance exercise training.

PMID- 15985527
TI  - A model for the role of short self-assembled peptides in the very early stages of
      the origin of life.
AB  - The molecular basis of the origin of life is one of the most fundamental
      questions in modern biology. While the "RNA world" hypothesis offers a very
      sensible model for the evolvement of the current biochemical networks, there is a
      lack of knowledge about the early steps that led to the formation of the first
      RNA molecules. This issue is essential as it is practically impossible that
      complex molecules as functional RNA oligonucleotides had evolved spontaneously.
      It was recently demonstrated that peptide molecules as simple as dipeptides can
      self-assemble into well-ordered tubular, fibrilar, and closed-cage structures.
      Other studies have confirmed the ability of dipeptides to act as catalysts and
      the capability of other peptides, as short as tripeptides, to serve as a template
      for nucleotide binding and orientation. Unlike complex RNA molecules, the
      spontaneous formation of functional short peptides in the primordial earth
      conditions is very likely. We suggest a novel mechanism for the origin of life
      that is based on the ability of short peptides to form encapsulated structures,
      catalyst chemical reaction, and serve as highly ordered template for the assembly
      of nucleotides. This model may explain the early events that led to the formation
      of the current biochemical machinery that combines the elaborated and coordinated
      interaction between nucleic acids and proteins to allow the function of living
      systems.

PMID- 15985526
TI  - Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis.
AB  - The molecular mechanisms by which obesity increases the risk of cardiovascular
      diseases are poorly understood. The purpose of this study was to identify
      candidate biomarkers overexpressed in adipose tissue of obese subjects that could
      link expanded fat mass to atherosclerosis. We compared gene expression profile in
      subcutaneous adipose tissue (scWAT) of 28 obese and 11 lean subjects using
      microarray technology. This analysis identified 240 genes significantly
      overexpressed in scWAT of obese subjects. The genes were then ranked according to
      the correlation between gene expression and body mass index (BMI). In this list,
      the elastolytic cysteine protease cathepsin S was among the highly correlated
      genes. RT-PCR and Western blotting confirmed the increase in cathepsin S mRNA
      (P=0.006) and protein (P<0.05) in obese scWAT. The circulating concentrations of
      cathepsin S were also significantly higher in obese than in nonobese subjects
      (P<0.0001). Both cathepsin S mRNA in scWAT and circulating levels were positively
      correlated with BMI, body fat, and plasma triglyceride levels. In addition, we
      show that the proinflammatory factors, lipopolysaccharide, interleukin-1beta, and
      tumor necrosis factor-alpha increase cathepsin S secretion in human scWAT
      explants. This study identifies cathepsin S as a novel marker of adiposity. Since
      this enzyme has been implicated in the development of atherosclerotic lesions, we
      propose that cathepsin S represents a molecular link between obesity and
      atherosclerosis.

PMID- 15985528
TI  - Embryonic implantation and leukocyte transendothelial migration: different
      processes with similar players?
AB  - A clear parallelism between the different steps in human embryo-endometrial
      apposition/adhesion/invasion and leukocyte-endothelium
      rolling/adhesion/extravasation can be established. During human implantation and
      leukocyte trafficking, a first wave of soluble mediators regulates the expression
      and functional activity of adhesion molecules such as L-selectin and integrins,
      which mediate both processes. Apical surfaces of human endometrial epithelium and
      endothelium are key elements for the initiation of molecular interactions to
      capture the blastocyst or leukocyte, respectively. Subsequently, the blastocyst
      and the leukocyte migrate through the epithelium and endothelium toward their
      final destination, the endometrial stroma, to initiate placentation or the
      inflammatory foci as part of the immune response. Similarities between the
      intermediate molecular mechanisms of these two physiologically unrelated
      processes are discussed.

PMID- 15985529
TI  - Nrf2, a multi-organ protector?
AB  - NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that
      binds to the promoter sequence "antioxidant responsive element (ARE)" leading to
      coordinated up-regulation of ARE-driven detoxification and antioxidant genes.
      Since the expression of a wide array of antioxidant and detoxification genes are
      positively regulated by the ARE sequence, Nrf2 may serve as a master regulator of
      the ARE-driven cellular defense system against oxidative stress. In support of
      this, numerous studies have shown that Nrf2 protects many cell types and organ
      systems from a broad spectrum of toxic insults and disease pathogenesis. This
      Nrf2-conferred, multi-organ protection phenomenon raises an interesting question
      about how a single protein can protect many different organs from various toxic
      insults. A possible molecular mechanism explaining this phenomenon is that Nrf2
      protects many different cell types by coordinately up-regulating classic ARE
      driven genes as well as cell type-specific target genes that are required for the
      defense system of each cell type in its unique environment. This hypothesis is
      supported by microarray data indicating the protective role of Nrf2 is conveyed
      through both known ARE-driven genes and novel cell type-specific genes. The
      widespread nature of Nrf2 may have an important therapeutic potential, allowing
      prevention of carcinogenesis and neurodegenerative diseases.

PMID- 15985530
TI  - Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the
      vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25
      dihydroxyvitamin D3.
AB  - The innate immune system of mammals provides a rapid response to repel assaults
      from numerous infectious agents including bacteria, viruses, fungi, and
      parasites. A major component of this system is a diverse combination of cationic
      antimicrobial peptides that include the alpha- and beta-defensins and
      cathelicidins. In this study, we show that 1,25-dihydroxyvitamin D3 and three of
      its analogs induced expression of the human cathelicidin antimicrobial peptide
      (CAMP) gene. This induction was observed in acute myeloid leukemia (AML),
      immortalized keratinocyte, and colon cancer cell lines, as well as normal human
      bone marrow (BM) -derived macrophages and fresh BM cells from two normal
      individuals and one AML patient. The induction occurred via a consensus vitamin D
      response element (VDRE) in the CAMP promoter that was bound by the vitamin D
      receptor (VDR). Induction of CAMP in murine cells was not observed and expression
      of CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-type levels.
      Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in
      a short interspersed nuclear element or SINE in the CAMP promoter of primates
      that was absent in the mouse, rat, and canine genomes. Our findings reveal a
      novel activity of 1,25-dihydroxyvitamin D3 and the VDR in regulation of primate
      innate immunity.

PMID- 15985531
TI  - Reactive oxygen species-dependent TNF-alpha converting enzyme activation through
      stimulation of 5-HT2B and alpha1D autoreceptors in neuronal cells.
AB  - A major determinant of neuronal homeostasis is the proper integration of cell
      signaling pathways recruited by a variety of neuronal and non-neuronal factors.
      By taking advantage of a neuroectodermal cell line (1C11) endowed with the
      capacity to differentiate into serotonergic (1C115-HT) or noradrenergic (1C11NE)
      neurons, we identified serotonin (5-hydroxytryptamine, 5-HT)- and norepinephrine
      (NE)-dependent signaling cascades possibly involved in neuronal functions. First,
      we establish that 5-HT2B receptors and 1D adrenoceptors are functionally coupled
      to reactive oxygen species (ROS) synthesis through NADPH oxidase activation in
      1C115-HT and 1C11NE cells. This observation constitutes the prime evidence that
      bioaminergic autoreceptors take part in the control of the cellular redox
      equilibrium in a neuronal context. Second, our data identify TACE (TNF-
      Converting Enzyme), a member of a disintegrin and metalloproteinase (ADAM)
      family, as a downstream target of the 5-HT2B and 1D receptor-NADPH oxidase
      signaling pathways. Upon 5-HT2B or 1D receptor stimulation, ROS fully govern TNF-
      shedding in the surrounding milieu of 1C115-HT or 1C11NE cells. Third, 5-HT2B and
      1Dreceptor couplings to the NADPH oxidase-TACE cascade are strictly restricted to
      1C11-derived progenies that have implemented a complete serotonergic or
      noradrenergic phenotype. Overall, these observations suggest that 5-HT2B and 1D
      autoreceptors may play a role in the maintenance of neuron- and neurotransmitter
      associated functions. Eventually, our study may have implications regarding the
      origin of oxidative stress as well as up-regulated expression of proinflammatory
      cytokines in neurodegenerative disorders, which may relate to the deviation of
      normal signaling pathways.

PMID- 15985532
TI  - Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion
      injury.
AB  - Mitochondrial oxidative damage contributes to a wide range of pathologies,
      including cardiovascular disorders and neurodegenerative diseases. Therefore,
      protecting mitochondria from oxidative damage should be an effective therapeutic
      strategy. However, conventional antioxidants have limited efficacy due to the
      difficulty of delivering them to mitochondria in situ. To overcome this problem,
      we developed mitochondria-targeted antioxidants, typified by MitoQ, which
      comprises a lipophilic triphenylphosphonium (TPP) cation covalently attached to a
      ubiquinol antioxidant. Driven by the large mitochondrial membrane potential, the
      TPP cation concentrates MitoQ several hundred-fold within mitochondria,
      selectively preventing mitochondrial oxidative damage. To test whether MitoQ was
      active in vivo, we chose a clinically relevant form of mitochondrial oxidative
      damage: cardiac ischemia-reperfusion injury. Feeding MitoQ to rats significantly
      decreased heart dysfunction, cell death, and mitochondrial damage after ischemia
      reperfusion. This protection was due to the antioxidant activity of MitoQ within
      mitochondria, as an untargeted antioxidant was ineffective and accumulation of
      the TPP cation alone gave no protection. Therefore, targeting antioxidants to
      mitochondria in vivo is a promising new therapeutic strategy in the wide range of
      human diseases such as Parkinson's disease, diabetes, and Friedreich's ataxia
      where mitochondrial oxidative damage underlies the pathology.

PMID- 15985533
TI  - Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial
      cell contraction by depolymerization of microtubules.
AB  - Smoking is a significant risk factor for development of atherosclerosis. However,
      the pathophysiology of smoking-mediated vessel wall damage is not understood.
      With tools ranging from analytical chemistry to cell biology, we show that
      cigarette smoke contains metals that catalyze the direct oxidation of cellular
      proteins by smoke oxidants. Oxidation of cellular proteins causes a loss of
      microtubule function, culminating in microtubule depolymerization and proteasome
      dependent degradation of alpha-tubulin. As a consequence of the microtubule
      collapse, cytoskeletal structures as well as intermediate filaments break down,
      leading finally to a contraction of vascular endothelial cells. We observed a
      smoke extract-induced, calpain-dependent degradation of the intracellular form of
      platelet-endothelial cell adhesion molecule 1/CD31, as well as a release of P
      selectin/CD62P, IL-6, and IL-8 from endothelial cells into the supernatant.
      Increased levels of soluble CD62P and IL-6 are well known to be associated with
      smoking in humans. Increased permeability of the vascular endothelium is a
      crucial event in atherogenesis. This work highlights the compounds and mechanisms
      by which cigarette smoke induces leakiness of the vascular endothelium.

PMID- 15985534
TI  - Transcript and metabolite analysis of the effects of tamoxifen in rat liver
      reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis.
AB  - Nonalcoholic steatohepatitis (NASH) is a common feature of the metabolic syndrome
      and toxic reactions to pharmacological drugs. Tamoxifen, (TMX) a widely used anti
      breast cancer drug, can induce NASH and changes in plasma cholesterol levels
      through mechanisms that are unclear. We studied primary actions of TMX using a
      short-term treatment (5 days) that induces microvesicular hepatic steatosis and
      marked hypercholesterolemia in male rats. Using a combined approach of gene
      expression profiling and NMR-based metabolite analysis, we found that TMX-treated
      livers have increased saturated fatty acid content despite changes in gene
      expression, indicating decreased de novo lipogenesis and increased fatty acid
      oxidation. Our results show that TMX predominantly down-regulates FAS expression
      and activity as indicated by the accumulation of malonyl-CoA, a known inhibitor
      of mitochondrial beta-oxidation. In the face of a continued supply of exogenous
      free fatty acids, the blockade of fatty acid oxidation produced by elevated
      malonyl-CoA is likely to be the major factor leading to steatosis. Use of a
      combination of metabolomic and transcriptomic analysis has allowed us to identify
      mechanisms underlying important metabolic side effects of a widely prescribed
      drug. Given the broader importance of hepatic steatosis, the novel molecular
      mechanism revealed in this study should be examined in other forms of steatosis
      and nonalcoholic steatohepatitis.

PMID- 15985535
TI  - Identification of proteins released by pancreatic cancer cells by
      multidimensional protein identification technology: a strategy for identification
      of novel cancer markers.
AB  - The purpose of this study is to identify novel proteins released by cancer cells
      that are involved in extracellular matrix (ECM) remodeling using small-volume
      samples and automated technology. We applied multidimensional protein
      identification technology (MudPIT), which incorporates two-dimensional capillary
      chromatography coupled to tandem mass spectrometry to small quantities of serum
      free supernatants of resting or phorbol ester-activated Suit-2 pancreatic cancer
      cells. Selected markers were validated in additional pancreatic cancer cell
      lines, primary cancers, and xenografted cancer cells. MudPIT analysis of 10
      microl of supernatants identified 46 proteins, 21 of which are classified as
      secreted, and 10 have never been associated with pancreatic cancer. These include
      CSPG2/versican, Mac25/angiomodulin, IGFBP-1, HSPG2/perlecan, syndecan 4, FAM3C,
      APLP2, cyclophilin B, beta2 microglobulin, and ICA69. Evidence that cancer cells
      release these proteins in vivo was obtained for CSPG2/versican and
      Mac25/angiomodulin by immunohistochemistry on both primary pancreatic cancers and
      in a model consisting of Suit-2 cells embedded in an amorphous matrix and
      implanted in athymic mice. MudPIT allowed efficient and rapid identification of
      proteins released by cancer cells, including molecules previously undescribed in
      the type of cancer analyzed. Our finding that pancreatic cancer cells secrete a
      series of proteoglycans, including versican, perlecan, syndecan 1 and 4,
      challenges the common view that fibroblasts of tumor stroma are the sole source
      of these molecules.

PMID- 15985536
TI  - The effects of intrinsic pathway protease deficiencies on plasminogen-deficient
      mice.
AB  - Plasminogen (Plg)-deficient mice experience wasting and have decreased longevity
      due to disseminated fibrin deposition. We generated mice with combined
      deficiencies of Plg and coagulation factor IX (fIX) or XI (fXI) to determine the
      effects on the Plg null phenotype. Mice lacking Plg and fIX (Plg(-/-)/fIX-/-)
      have lower mortality at age 6 months than Plg(-/-)/fIX+/+ mice (15% and 67%,
      respectively) and less severe wasting, consistent with the importance of fIX in
      fibrin formation. In contrast, combined Plg and fXI deficiency (Plg(-/-)/fXI-/-)
      reduces life span (more than 90% mortality at 6 months) and is associated with
      leukocyte infiltration of the lungs and pulmonary fibrosis. These abnormalities
      are not seen in Plg-/- or Plg(-/-)/fIX-/- animals. Activated fXI is thought to
      function primarily as a fIX activator; however, our observation suggests that fXI
      may have functions in regulation of inflammation or tissue repair distinct from
      its role in coagulation.

PMID- 15985537
TI  - Sustained response and long-term safety of eculizumab in paroxysmal nocturnal
      hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a hematologic disorder characterized
      by clonal expansion of red blood cells (RBCs) lacking the ability to inhibit
      complement-mediated hemolysis. Eculizumab, a humanized monoclonal antibody that
      binds the C5 complement protein, blocks serum hemolytic activity. This study
      evaluated the long-term safety and efficacy of eculizumab in 11 patients with PNH
      during an open-label extension trial. After completion of an initial 12-week
      study, all patients chose to participate in the 52-week extension study.
      Eculizumab, administered at 900 mg every 12 to 14 days, was sufficient to
      completely and consistently block complement activity in all patients. A dramatic
      reduction in hemolysis was maintained throughout the study, with a decrease in
      lactate dehydrogenase (LDH) levels from 3110.7 IU/L before treatment to 622.4
      IU/L (P = .002). The proportion of PNH type III RBCs increased from 36.7% at
      baseline to 58.4% (P = .005). The paroxysm rate of days with gross evidence of
      hemoglobinuria per patient each month decreased from 3.0 during screening to 0.2
      (P < .001) during treatment. The median transfusion rate decreased from 1.8 U per
      patient each month before eculizumab treatment to 0.3 U per patient each month (P
      = .001) during treatment. Statistically significant improvements in quality-of
      life measures were also maintained during the extension study. Eculizumab
      continued to be safe and well tolerated, and all patients completed the study.
      The close relationship between sustained terminal complement inhibition,
      hemolysis, and symptoms was demonstrated.

PMID- 15985539
TI  - Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome.
AB  - Rare cases of somatic mosaicism resulting from reversion of inherited mutations
      can lead to the attenuation of blood-cell disorders, including Wiskott-Aldrich
      syndrome (WAS). The impact of the revertant hematopoietic stem or progenitor
      cells, particularly their representation in blood-cell populations, is of
      interest because it predicts the outcome of gene therapy. Here we report an 8
      year-old patient with WAS caused by a single nucleotide insertion in the WASP
      gene that abrogates protein expression. The patient nonetheless had mild disease.
      We found reversion of the mutation in a fraction of patient lymphocytes. Forty
      percent of natural killer (NK) cells expressed Wiskott-Aldrich syndrome protein
      (WASP), and NK cells contained both mutated and revertant (normal) sequences.
      WASP was not expressed in patient T or B cells; T cells contained only the
      mutated sequence. The selective advantage of WASP+ NK cells was also demonstrated
      for carrier females. The enrichment of WASP+-revertant NK cells indicates that
      WASP provides a selective advantage in this lineage and predicts the success of
      gene therapy for reconstituting the NK-cell compartment. The importance of
      reconstituting the NK-cell lineage is discussed.

PMID- 15985538
TI  - Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in
      myeloid leukemia.
AB  - CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors
      that regulate cell growth and differentiation in numerous cell types. To identify
      novel C/EBP-target genes, we performed transcriptional profiling using inducible
      NIH 3T3 cell lines expressing 1 of 4 members of the C/EBP family. Functional
      analysis revealed a previously unknown link between C/EBP proteins and circadian
      clock genes. Our microarray data showed that the expression levels of 2 core
      components of the circadian network, Per2 and Rev-Erbalpha, were significantly
      altered by C/EBPs. Recent studies suggested that Per2 behaves as a tumor
      suppressor gene in mice. Therefore, we focused our additional studies on Per2. We
      showed that Per2 expression is up-regulated by C/EBPalpha and C/EBPepsilon. Per2
      levels were reduced in lymphoma cell lines and in acute myeloid leukemia (AML)
      patient samples. In addition, we generated stable K562 cells that expressed an
      inducible Per2 gene. Induction of Per2 expression resulted in growth inhibition,
      cell cycle arrest, apoptosis, and loss of clonogenic ability. These results
      suggest that Per2 is a downstream C/EBPalpha-target gene involved in AML, and its
      disruption might be involved in initiation and/or progression of AML.

PMID- 15985540
TI  - The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene
      expression in human erythroid cells.
AB  - Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is
      thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing
      the maturation of erythroid precursors. The molecular mechanisms involved in HU
      mediated regulation of gamma-globin expression are currently unclear. We
      identified an HU-induced small guanosine triphosphate (GTP)-binding protein,
      secretion-associated and RAS-related (SAR) protein, in adult erythroid cells
      using differential display. Stable SAR expression in K562 cells increased gamma
      globin mRNA expression and resulted in macrocytosis. The cells appeared immature.
      SAR-mediated induction of gamma-globin also inhibited K562 cell growth by causing
      arrest in G1/S, apoptosis, and delay of maturation, cellular changes consistent
      with the previously known effects of HU on erythroid cells. SAR also enhanced
      both gamma- and beta-globin transcription in primary bone marrow CD34+ cells,
      with a greater effect on gamma-globin than on beta-globin. Although up-regulation
      of GATA-2 and p21 was observed both in SAR-expressing cells and HU-treated K562
      cells, phosphatidylinositol 3 (PI3) kinase and phosphorylated ERK were inhibited
      specifically in SAR-expressing cells. These data reveal a novel role of SAR
      distinct from its previously known protein-trafficking function. We suggest that
      SAR may participate in both erythroid cell growth and gamma-globin production by
      regulating PI3 kinase/extracellular protein-related kinase (ERK) and GATA-2/p21
      dependent signal transduction pathways.

PMID- 15985541
TI  - Botrocetin/VWF-induced signaling through GPIb-IX-V produces TxA2 in an
      alphaIIbbeta3- and aggregation-independent manner.
AB  - Binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein (GP)
      Ib-IX-V complex initiates a signaling cascade that causes alphaIIbbeta3
      activation and platelet aggregation. Previous work demonstrated that botrocetin
      (bt)/VWF-mediated agglutination activates alphaIIbbeta3 and elicits adenosine
      triphosphate (ATP) secretion in a thromboxane A2 (TxA2)- and Ca2+-dependent
      manner. This agglutination-elicited TxA2 production occurs in the absence of ATP
      secretion. However, the signaling components and signaling network or pathway
      activated by GPIb-mediated agglutination to cause TxA2 production have not been
      identified. Therefore, the focus of this study was to elucidate at least part of
      the signal transduction network or pathway activated by GPIb-mediated
      agglutination to cause TxA2 production. The phosphatidylinositol 3-kinase (PI3K)
      selective inhibitor wortmannin, and mouse platelets deficient in Lyn, Src, Syk,
      Src homology 2 (SH2) domain-containing leukocyte protein 76 (SLP-76),
      phospholipase Cgamma2 (PLCgamma2), linker for activation of T cells (LAT), or Fc
      receptor gamma-chain (FcRgamma-chain) were used for these studies. LAT and
      FcRgamma-chain were found not to be required for agglutination-driven TxA2
      production or activation of alphaIIbbeta3, but were required for granule
      secretion and aggregation. The results also clearly demonstrate that bt/VWF
      mediated agglutination-induced TxA2 production is dependent on signaling
      apparently initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76,
      PI3K, PLCgamma2, and protein kinase C (PKC).

PMID- 15985543
TI  - Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular
      weight heparin thromboprophylaxis: a meta-analysis.
AB  - Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially devastating
      complication of anticoagulation with unfractionated heparin (UFH) or low
      molecular-weight heparin (LMWH). Our objective was to determine and compare the
      incidences of HIT in surgical and medical patients receiving thromboprophylaxis
      with either UFH or LMWH. All relevant studies identified in the MEDLINE database
      (1984-2004), not limited by language, and from reference lists of key articles
      were evaluated. Randomized and nonrandomized controlled trials comparing
      prophylaxis with UFH and LMWH and measuring HIT or thrombocytopenia as outcomes
      were included. Two reviewers independently extracted data on thromboprophylaxis
      (type, dose, frequency, and duration), definition of thrombocytopenia, HIT assay,
      and rates of the following outcomes: HIT, thrombocytopenia, and thromboembolic
      events. HIT was defined as a decrease in platelets to less than 50% or to less
      than 100 x 10(9)/L and positive laboratory HIT assay. Fifteen studies (7287
      patients) were eligible: 2 randomized controlled trials (RCTs) measuring HIT
      (1014 patients), 3 prospective studies (1464 patients) with nonrandomized
      comparison groups in which HIT was appropriately measured in both groups, and 10
      RCTs (4809 patients) measuring thrombocytopenia but not HIT. Three analyses were
      performed using a random effects model and favored the use of LMWH: (1) RCTs
      measuring HIT showed an odds ratio (OR) of 0.10 (95% confidence interval [CI],
      0.01-0.2; P = .03); (2) prospective studies measuring HIT showed an OR of 0.10
      (95% CI, 0.03-0.33; P < .001); (3) all 15 studies measured thrombocytopenia. The
      OR was 0.47 (95% CI, 0.22-1.02; P = .06). The inverse variance-weighted average
      that determined the absolute risk for HIT with LMWH was 0.2%, and with UFH the
      risk was 2.6%. Most studies were of patients after orthopedic surgery.

PMID- 15985542
TI  - Hemolysis-associated priapism in sickle cell disease.
AB  - Priapism, although uncommon in the general population, is one of the many serious
      complications associated with sickle cell disease (SCD). Few studies have
      described the clinical and hematologic characteristics of individuals with
      priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease,
      we assembled 273 case subjects with priapism and 979 control subjects. Case
      subjects, compared with control subjects, had significantly lower levels of
      hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate
      aminotransferase; and higher reticulocyte, white blood cell, and platelet counts.
      These findings suggest an association of priapism with increased hemolysis.
      Hemolysis decreases the availability of circulating nitric oxide, which plays an
      important role in erectile function.

PMID- 15985544
TI  - The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar
      cohort of MPD patients.
AB  - Recently, a Jak2V617F mutation has been described in the vast majority of
      patients with polycythemia vera (PV) as well as in subsets of patients with
      essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). The question
      arises whether this mutation is observed in those patients with ET and IMF who
      have also displayed previously described molecular markers, notably the ability
      to form endogenous erythroid colonies (EECs), overexpression of polycythemia
      rubra vera 1 (PRV-1), and decreased c-Mpl expression. We therefore analyzed the
      Janus kinase 2 (Jak2) DNA sequence, EEC growth, PRV-1 expression, and c-Mpl
      (myeloproliferative) levels in a cohort of 78 myeloproliferative disorder (MPD)
      patients (42 ET, 22 PV, and 14 IMF). Presence of the Jak2V617F mutation was very
      highly correlated with PRV-1 overexpression and the ability to form EECs in all 3
      subtypes of MPDs (P < .001). (

PMID- 15985545
TI  - Only a specific subset of human peripheral-blood monocytes has endothelial-like
      functional capacity.
AB  - The monocyte population in blood is considered a possible source of endothelial
      precursors. Because endothelial-specific receptor tyrosine kinases act as
      regulators of endothelial cell function, we investigated whether expression of
      the vascular endothelial growth factor receptor-2 (VEGFR-2) on monocytes is
      important for their endothelial-like functional capacity. Peripheral-blood
      monocytes expressing vascular endothelial growth factor receptor-2 (VEGFR-2), or
      CD14+/VEGFR-2+, were isolated, and their phenotypic, morphologic, and functional
      capacities were compared with those of monocytes negative for this marker
      (CD14+/VEGFR-2-). CD14+/VEGFR-2+ cells constituted approximately 2% +/- 0.5% of
      the total population of monocytes and 0.08% +/- 0.04% of mononuclear cells in
      blood. CD14+/VEGFR-2+ cells exhibited the potential to differentiate in vitro
      into cells with endothelial characteristics. The cells were efficiently
      transduced by a lentiviral vector driving expression of the green fluorescence
      protein (GFP). Transplantation of GFP-transduced cells into balloon-injured
      femoral arteries of nude mice significantly contributed to efficient
      reendothelialization. CD14+/VEGFR-2- did not exhibit any of these
      characteristics. These data demonstrate that the expression of VEGFR-2 on
      peripheral blood monocytes is essential for their endothelial-like functional
      capacity and support the notion of a common precursor for monocytic and
      endothelial cell lineage. Our results help clarify which subpopulations may
      restore damaged endothelium and may participate in the maintenance of vascular
      homeostasis.

PMID- 15985546
TI  - A secreted regulatory protein couples transcription to the secretory activity of
      the Pseudomonas aeruginosa type III secretion system.
AB  - The type III secretion system (T3SS) of Pseudomonas aeruginosa is an important
      virulence determinant. Transcription of the T3SS is highly regulated and
      intimately coupled to the activity of the type III secretion channel. The
      secretion channel is generally closed, and transcription is repressed. Inducing
      signals such as calcium depletion, however, open the secretion channel and
      derepress transcription of the T3SS. The coupling of transcription with secretion
      requires three previously identified cytoplasmic regulatory proteins. ExsA is a
      DNA-binding protein required for transcriptional activation of the entire T3SS.
      The second regulatory protein, ExsD, functions as anti-activator by directly
      binding to ExsA. Finally, ExsC functions as an anti-anti-activator by directly
      binding to and inhibiting ExsD. Although the regulatory roles of ExsC, ExsD, and
      ExsA were defined through these previous studies, the mechanism of coupling
      transcription to secretion was unclear. We now report the identification of ExsE
      as a secreted regulator of the T3SS and provide evidence that ExsE functions as a
      direct inhibitor of ExsC. When the secretion channel is closed, ExsE is complexed
      with ExsC in the cytoplasm, and transcription of the T3SS is repressed by
      sequestration of ExsA by ExsD. We propose that the secretion of ExsE provides an
      initiating signal that results in an equilibrium shift whereby ExsC becomes
      preferentially bound to ExsD, thus allowing liberated ExsA to activate
      transcription of the T3SS. The presence of ExsE homologs in the T3SSs of other
      bacterial species suggests that this mechanism of coupling transcription to
      secretion may be commonly used.

PMID- 15985547
TI  - Initial synthesis and structure of an all-ferrous analogue of the fully reduced
      [Fe4S4]0 cluster of the nitrogenase iron protein.
AB  - The synthetic cubane-type iron-sulfur clusters [Fe(4)S(4)(SR)(4)](z) form a four
      member electron transfer series (z = 3-, 2-, 1-, and 0), all members of which
      except that with z = 0 have been isolated and characterized. They serve as
      accurate analogues of protein-bound [Fe(4)S(4)(SCys)(4)](z) redox centers, which,
      in terms of core oxidation states, exhibit the redox couples [Fe(4)S(4)](3+/2+)
      and [Fe(4)S(4)](2+/1+). Clusters with the all-ferrous core [Fe(4)S(4)](0) have
      never been isolated because of their oxidative sensitivity. Recent work on the Fe
      protein of Azotobacter vinelandii nitrogenase has demonstrated the formation of
      the all-ferrous state upon reaction with a strong reductant. Treatment of the
      cyanide cluster [Fe(4)S(4)(CN)(4)](3-) with K[Ph(2)CO] in
      acetonitrile/tetrahydrofuran affords the all-ferrous cluster [Fe(4)S(4)(CN)(4)](4
      ), isolated as the Bu(4)N(+) salt. The x-ray structure demonstrates retention of
      a cubane-type structure with idealized D(2)(d) symmetry. The Mossbauer spectrum
      unambiguously demonstrates the [Fe(4)S(4)](0) oxidation state. Bond distances,
      core volumes, (57)Fe isomer shifts, and visible absorption spectra make evident
      the high degree of structural and electronic similarity with the fully reduced Fe
      protein. The attribute of cyanide ligation causes positive [Fe(4)S(4)](2+/1+) and
      [Fe(4)S(4)](1+/0) redox potential shifts, facilitating the initial isolation of
      an analogue of the [Fe(4)S(4)](0) protein site.

PMID- 15985549
TI  - A modular microfluidic architecture for integrated biochemical analysis.
AB  - Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture
      are presented. The architecture is conceptualized on two levels: a single-chip
      level and a multiple-chip module (MCM) system level. At the individual chip
      level, a multilayer approach segregates components belonging to two fundamental
      categories: passive fluidic components (channels and reaction chambers) and
      active electromechanical control structures (sensors and actuators). This
      distinction is explicitly made to simplify the development process and minimize
      cost. Components belonging to these two categories are built separately on
      different physical layers and can communicate fluidically via cross-layer
      interconnects. The chip that hosts the electromechanical control structures is
      called the microfluidic breadboard (FBB). A single LOC module is constructed by
      attaching a chip comprised of a custom arrangement of fluid routing channels and
      reactors (passive chip) to the FBB. Many different LOC functions can be achieved
      by using different passive chips on an FBB with a standard resource
      configuration. Multiple modules can be interconnected to form a larger LOC system
      (MCM level). We demonstrated the utility of this architecture by developing
      systems for two separate biochemical applications: one for detection of protein
      markers of cancer and another for detection of metal ions. In the first case,
      free prostate-specific antigen was detected at 500 aM concentration by using a
      nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second
      case, we used a DNAzyme-based biosensor to identify the presence of Pb(2+) (lead)
      at a sensitivity of 500 nM in <1 nl of solution.

PMID- 15985548
TI  - Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant
      synthesizing modified teichoic acids.
AB  - Teichoic acids (TAs), and especially lipoteichoic acids (LTAs), are one of the
      main immunostimulatory components of pathogenic Gram-positive bacteria. Their
      contribution to the immunomodulatory properties of commensal bacteria and
      especially of lactic acid bacteria has not yet been investigated in detail. To
      evaluate the role of TAs in the interaction between lactic acid bacteria and the
      immune system, we analyzed the antiinflammatory properties of a mutant of
      Lactobacillus plantarum NCIMB8826 affected in the TA biosynthesis pathway both in
      vitro (mononuclear cells stimulation) and in vivo (murine model of colitis). This
      Dlt- mutant was found to incorporate much less D-Ala in its TAs than the WT
      strain. This defect significantly impacted the immunomodulation reactions induced
      by the bacterium, as shown by a dramatically reduced secretion of proinflammatory
      cytokines by peripheral blood mononuclear cells and monocytes stimulated by the
      Dlt- mutant as compared with the parental strain. Concomitantly, a significant
      increase in IL-10 production was stimulated by the Dlt- mutant in comparison with
      the WT strain. Moreover, the proinflammatory capacity of L. plantarum-purified
      LTA was found to be Toll-like receptor 2-dependent. Consistent with the in vitro
      results, the Dlt- mutant was significantly more protective in a murine colitis
      model than its WT counterpart. The results indicated that composition of LTA
      within the whole-cell context of L. plantarum can modulate proinflammatory or
      antiinflammatory immune responses.

PMID- 15985550
TI  - Continuous attraction toward phonological competitors.
AB  - Certain models of spoken-language processing, like those for many other
      perceptual and cognitive processes, posit continuous uptake of sensory input and
      dynamic competition between simultaneously active representations. Here, we
      provide compelling evidence for this continuity assumption by using a continuous
      response, hand movements, to track the temporal dynamics of lexical activations
      during real-time spoken-word recognition in a visual context. By recording the
      streaming x, y coordinates of continuous goal-directed hand movement in a spoken
      language task, online accrual of acoustic-phonetic input and competition between
      partially active lexical representations are revealed in the shape of the
      movement trajectories. This hand-movement paradigm allows one to project the
      internal processing of spoken-word recognition onto a two-dimensional layout of
      continuous motor output, providing a concrete visualization of the attractor
      dynamics involved in language processing.

PMID- 15985551
TI  - Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and
      glycogen synthase kinase 3beta is required for adipogenesis.
AB  - CCAAT enhancer-binding protein (C/EBP)beta, C/EBPalpha, and peroxisome
      proliferator activated receptor (PPAR)gamma act in a cascade where C/EBPbeta
      activates expression of C/EBPalpha and PPARgamma, which then function as
      pleiotropic activators of genes that produce the adipocyte phenotype. When growth
      arrested 3T3-L1 preadipocytes are induced to differentiate, C/EBPbeta is rapidly
      expressed but still lacks DNA-binding activity. After a long (14-hour) lag,
      glycogen synthase kinase 3beta enters the nucleus, which correlates with
      hyperphosphorylation of C/EBPbeta and acquisition of DNA-binding activity.
      Concurrently, 3T3-L1 preadipocytes synchronously enter S phase and undergo
      mitotic clonal expansion, a prerequisite for terminal differentiation. Ex vivo
      and in vitro experiments with C/EBPbeta show that phosphorylation of Thr-188 by
      mitogen-activating protein kinase "primes" C/EBPbeta for subsequent
      phosphorylation on Ser-184 and Thr-179 by glycogen synthase kinase 3beta,
      acquisition of DNA-binding function, and transactivation of the C/EBPalpha and
      PPARgamma genes. The delayed transactivation of the C/EBPalpha and PPARgamma
      genes by C/EBPbeta appears necessary to allow mitotic clonal expansion, which
      would otherwise be prevented, because C/EBPalpha and PPARgamma are antimitotic.

PMID- 15985552
TI  - Nonmetabolizable analogue of 2-oxoglutarate elicits heterocyst differentiation
      under repressive conditions in Anabaena sp. PCC 7120.
AB  - In response to combined nitrogen starvation in the growth medium, the filamentous
      cyanobacterium Anabaena sp. PCC 7120 is able to develop a particular cell type,
      called a heterocyst, specialized in molecular nitrogen fixation. Heterocysts are
      regularly intercalated among vegetative cells and represent 5-10% of all cells
      along each filament. In unicellular cyanobacteria, the key Krebs cycle
      intermediate, 2-oxoglutarate (2-OG), has been suggested as a nitrogen status
      signal, but in vivo evidence is still lacking. In this study we show that
      nitrogen starvation causes 2-OG to accumulate transiently within cells of
      Anabaena PCC 7120, reaching a maximal intracellular concentration of
      approximately 0.1 mM 1 h after combined nitrogen starvation. A nonmetabolizable
      fluorinated 2-OG derivative, 2,2-difluoropentanedioic acid (DFPA), was
      synthesized and used to demonstrate the signaling function of 2-OG in vivo. DFPA
      is shown to be a structural analogue of 2-OG and the process of its uptake and
      accumulation in vivo can be followed by (19)F magic angle spinning NMR because of
      the presence of the fluorine atom and its chemical stability. DFPA at a threshold
      concentration of 0.3 mM triggers heterocyst differentiation under repressing
      conditions. The multidisciplinary approaches using synthetic fluorinated
      analogues, magic angle spinning NMR for their analysis in vivo, and techniques of
      molecular biology provide a powerful means to identify the nature of the signals
      that remain unknown or poorly defined in many signaling pathways.

PMID- 15985553
TI  - Kinetic suppression of microtubule dynamic instability by griseofulvin:
      implications for its possible use in the treatment of cancer.
AB  - The antifungal drug griseofulvin inhibits mitosis strongly in fungal cells and
      weakly in mammalian cells by affecting mitotic spindle microtubule (MT) function.
      Griseofulvin also blocks cell-cycle progression at G(2)/M and induces apoptosis
      in human tumor cell lines. Despite extensive study, the mechanism by which the
      drug inhibits mitosis in human cells remains unclear. Here, we analyzed the
      ability of griseofulvin to inhibit cell proliferation and mitosis and to affect
      MT polymerization and organization in HeLa cells together with its ability to
      affect MT polymerization and dynamic instability in vitro. Griseofulvin inhibited
      cell-cycle progression at prometaphase/anaphase of mitosis in parallel with its
      ability to inhibit cell proliferation. At its mitotic IC(50) of 20 muM, spindles
      in blocked cells displayed nearly normal quantities of MTs and MT organization
      similar to spindles blocked by more powerful MT-targeted drugs. Similar to
      previously published data, we found that very high concentrations of griseofulvin
      (>100 microM) were required to inhibit MT polymerization in vitro. However, much
      lower drug concentrations (1-20 microM) strongly suppressed the dynamic
      instability behavior of the MTs. We suggest that the primary mechanism by which
      griseofulvin inhibits mitosis in human cells is by suppressing spindle MT
      dynamics in a manner qualitatively similar to that of much more powerful
      antimitotic drugs, including the vinca alkaloids and the taxanes. In view of
      griseofulvin's lack of significant toxicity in humans, we further suggest that it
      could be useful as an adjuvant in combination with more powerful drugs for the
      treatment of cancer.

PMID- 15985554
TI  - A tumor necrosis factor receptor family protein serves as a cellular receptor for
      the macrophage-tropic equine lentivirus.
AB  - Characterization of cellular receptors for human, simian, and feline
      immunodeficiency viruses that are tropic for lymphocytes and macrophages have
      revealed a common theme of a sequential binding of viral envelope proteins with
      two coreceptors to mediate virus infection of target cells. In contrast to these
      dual tropic immunodeficiency viruses, the ungulate lentiviruses, including equine
      infectious anemia virus (EIAV), exclusively infect cells of the monocyte
      macrophage lineage to cause progressive degenerative diseases without clinical
      immunodeficiency. EIAV causes a uniquely dynamic disease that is characterized by
      recurrent disease episodes including fever, diarrhea, lethargy, anemia, and
      thrombocytopenia. Although EIAV provides an important animal model for lentivirus
      disease resulting from macrophage infection, to date there has been no definition
      of the specific cellular receptor(s) used by the equine lentivirus to infect
      target cells. In the current study, we have identified and cloned a functional
      receptor for EIAV, designated equine lentivirus receptor-1 (ELR1), related to the
      family of TNF receptor (TNFR) proteins. ELR1 was shown to be expressed in various
      equine cells permissive for EIAV replication in vitro, including monocytes and
      macrophages. In contrast, EIAV-resistant human, murine, and simian cells were
      negative for ELR1 expression but became susceptible to virus infection when
      transduced with a recombinant murine retrovirus expressing the ELR1. Thus, these
      results identify a specific functional receptor for a macrophagetropic lentivirus
      and indicate that infection by EIAV may be mediated by a single receptor, in
      contrast to coreceptors used by the lymphotropic immunodeficiency lentiviruses.

PMID- 15985555
TI  - Complex-periodic spiral waves in confluent cardiac cell cultures induced by
      localized inhomogeneities.
AB  - Spatiotemporal wave activities in excitable heart tissues have long been the
      subject of numerous studies because they underlie different forms of cardiac
      arrhythmias. In particular, understanding the dynamics and the instabilities of
      spiral waves have become very important because they can cause reentrant
      tachycardia and their subsequent transitions to fibrillation. Although many
      aspects of cardiac spiral waves have been investigated through experiments and
      model simulations, their complex properties are far from well understood. Here,
      we show that intriguing complex-periodic (such as period-2, period-3, period-4,
      or aperiodic) spiral wave states can arise in monolayer tissues of cardiac cell
      culture in vitro, and demonstrate that these different dynamic states can coexist
      with abrupt and spontaneous transitions among them without any change in system
      parameters; in other words, the medium supports multistability. Based on
      extensive image data analysis, we have confirmed that these spiral waves are
      driven by their tips tracing complex orbits whose unusual, meandering shapes are
      formed by delicate interplay between localized conduction blocks and nonlinear
      properties of the culture medium.

PMID- 15985556
TI  - Replication-associated strand asymmetries in mammalian genomes: toward detection
      of replication origins.
AB  - In the course of evolution, mutations do not affect both strands of genomic DNA
      equally. This imbalance mainly results from asymmetric DNA mutation and repair
      processes associated with replication and transcription. In prokaryotes,
      prevalence of G over C and T over A is frequently observed in the leading strand.
      The sign of the resulting TA and GC skews changes abruptly when crossing
      replication-origin and termination sites, producing characteristic step-like
      transitions. In mammals, transcription-coupled skews have been detected, but so
      far, no bias has been associated with replication. Here, analysis of intergenic
      and transcribed regions flanking experimentally identified human replication
      origins and the corresponding mouse and dog homologous regions demonstrates the
      existence of compositional strand asymmetries associated with replication.
      Multiscale analysis of human genome skew profiles reveals numerous transitions
      that allow us to identify a set of 1,000 putative replication initiation zones.
      Around these putative origins, the skew profile displays a characteristic jagged
      pattern also observed in mouse and dog genomes. We therefore propose that in
      mammalian cells, replication termination sites are randomly distributed between
      adjacent origins. Taken together, these analyses constitute a step toward genome
      wide studies of replication mechanisms.

PMID- 15985557
TI  - Modeling attacks on the food supply.

PMID- 15985558
TI  - Analyzing a bioterror attack on the food supply: the case of botulinum toxin in
      milk.
AB  - We developed a mathematical model of a cows-to-consumers supply chain associated
      with a single milk-processing facility that is the victim of a deliberate release
      of botulinum toxin. Because centralized storage and processing lead to
      substantial dilution of the toxin, a minimum amount of toxin is required for the
      release to do damage. Irreducible uncertainties regarding the dose-response curve
      prevent us from quantifying the minimum effective release. However, if terrorists
      can obtain enough toxin, and this may well be possible, then rapid distribution
      and consumption result in several hundred thousand poisoned individuals if
      detection from early symptomatics is not timely. Timely and specific in-process
      testing has the potential to eliminate the threat of this scenario at a cost of
      <1 cent per gallon and should be pursued aggressively. Investigation of improving
      the toxin inactivation rate of heat pasteurization without sacrificing taste or
      nutrition is warranted.

PMID- 15985559
TI  - Long term follow up of patients treated for Helicobacter pylori infection.
AB  - BACKGROUND: Helicobacter pylori infection induces progressive inflammatory
      changes in the gastric mucosa that may lead to gastric cancer. Understanding long
      term effects resulting from the cure of this infection is needed to design cancer
      prevention strategies. METHODS: A cohort of 795 adults with preneoplastic gastric
      lesions was randomised to receive anti-H pylori treatment and/or antioxidants. At
      the end of six years of intervention, those who did not receive anti-H pylori
      treatment were offered it. Gastric biopsies were obtained at baseline, and at 3,
      6, and 12 years. A histopathology score was utilised to document changes in
      gastric lesions. Non-linear mixed models were used to estimate the cumulative
      effect of H pylori clearance on histopathology scores adjusted for follow up
      time, interventions, and confounders. RESULTS: Ninety seven per cent of subjects
      were H pylori positive at baseline, and 53% were positive at 12 years. Subjects
      accumulated 1703 person years free of infection. A multivariate model showed a
      significant regression in histopathology score as a function of the square of H
      pylori negative time. Subjects who were H pylori negative had 14.8% more
      regression and 13.7% less progression than patients who were positive at 12 years
      (p = 0.001). The rate of healing of gastric lesions occurred more rapidly as
      years free of infection accumulated, and was more pronounced in less advanced
      lesions. CONCLUSIONS: Preneoplastic gastric lesions regress at a rate equal to
      the square of time in patients rendered free of H pylori infection. Our findings
      suggest that patients with preneoplastic gastric lesions should be treated and
      cured of their H pylori infection.

PMID- 15985560
TI  - Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and
      antro-pyloro-duodenal motility in humans.
AB  - BACKGROUND: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP
      1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay
      of gastric emptying. AIMS: To assess the effects of endogenous GLP-1 on endocrine
      pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1
      receptor antagonist exendin(9-39)amide (ex(9-39)NH2). METHODS: Nine healthy
      volunteers underwent four experiments each. In two experiments with and without
      intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was
      followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the
      higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was
      measured by perfusion manometry. To calculate the incretin effect (that is, the
      proportion of plasma insulin stimulated by intestinal hormones) the glycaemia
      observed during the luminal glucose experiments was mimicked using intravenous
      glucose in two further experiments. RESULTS: Ex(9-39)NH2 significantly increased
      glycaemia during fasting and duodenal glucose. It diminished plasma insulin
      during duodenal glucose and significantly reduced the incretin effect by
      approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and
      abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2
      markedly stimulated antroduodenal contractility. At low duodenal glucose it
      reduced the stimulation of tonic and phasic pyloric motility. At the high
      duodenal glucose load it abolished pyloric stimulation. CONCLUSIONS: Endogenous
      GLP-1 stimulates postprandial insulin release. The pancreatic alpha cell is under
      the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon.
      GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial
      inhibition of antral and stimulation of pyloric motility. We therefore suggest
      GLP-1 as a true incretin hormone and enterogastrone in humans.

PMID- 15985561
TI  - CRF2 receptor activation prevents colorectal distension induced visceral pain and
      spinal ERK1/2 phosphorylation in rats.
AB  - BACKGROUND AND AIMS: Activation of corticotropin releasing factor 1 (CRF1)
      receptors is involved in stress related responses and visceral pain, while
      activation of CRF2 receptors dampens the endocrine and some behavioural stress
      responses. We hypothesised that CRF2 receptor activation may influence visceral
      pain induced by colorectal distension (CRD) in conscious rats, and assessed the
      possible sites and mechanisms of action. METHODS: Male Sprague-Dawley rats were
      exposed to CRDs (60 mm Hg, 10 minutes twice, with a 10 minute rest interval).
      Visceromotor responses (VMR) were measured by electromyography or visual
      observation. Spinal (L6-S1) extracellular signal regulated kinase 1/2 (ERK 1/2)
      activation following in vivo CRD and CRF2 receptor gene expression in the T13-S1
      dorsal root ganglia (DRG) and spinal cord were determined. Inferior splanchnic
      afferent (ISA) activity to CRD (0.4 ml, 20 seconds) was assessed by
      electrophysiological recording in an in vitro ISA nerve-inferior mesenteric
      artery (intra-arterial)-colorectal preparation. RESULTS: In controls, VMR to the
      second CRD was mean 31 (SEM 4)% higher than that of the first (p<0.05). The
      selective CRF2 agonist, human urocortin 2 (hUcn 2, at 10 and 20 microg/kg),
      injected intravenous after the first distension, prevented sensitisation and
      reduced the second response by 8 (1)% and 30 (5)% (p<0.05) compared with the
      first response, respectively. RT-PCR detected CRF2 receptor gene expression in
      the DRG and spinal cord. CRD (60 mm Hg for 10 minutes) induced phosphorylation of
      ERK 1/2 in neurones of lumbosacral laminae I and IIo and the response was
      dampened by intravenous hUcn 2. CRD, in vitro, induced robust ISA spike activity
      that was dose dependently blunted by hUcn 2 (1-3 microg, intra-arterially). The
      CRF2 receptor antagonist, astressin2-B (200 microg/kg subcutaneously or 20 microg
      intra-arterially) blocked the hUcn 2 inhibitory effects in vivo and in vitro.
      CONCLUSIONS: Peripheral injection of hUcn 2 blunts CRD induced visceral pain,
      colonic afferent, and spinal L6-S1 ERK 1/2 activity through CRF2 receptor
      activation in rats.

PMID- 15985562
TI  - A remarkable permeability of canalicular tight junctions might facilitate
      retrograde, non-viral gene delivery to the liver via the bile duct.
AB  - AIMS: To establish the extent of retrograde bile duct infusion at an
      ultrastructural level, as a preliminary step before evaluating the efficacy of
      gene delivery to the rat liver via a branch of the bile duct. METHODS: The extent
      of retrograde infusion into the biliary tree was established by light and
      electron microscopy, following infusion of 10 nm gold particles into the right
      lateral lobe. Canalicular permeability was further assessed by the infusion of a
      67 kDa protein. For gene delivery, both naked DNA and a synthetic peptide vector
      system were evaluated. Because canalicular tight junction permeability can be
      compromised in damaged livers, both normal rats and rats recovering from the
      hepatotoxin D-galactosamine were studied. RESULTS: The gold particles penetrated
      the peripheral one third of the hepatic lobules and, surprisingly, reached the
      space of Disse in normal rats. Equally surprisingly, blood levels of a 67 kDa
      protein were identical after bile duct infusion and portal vein injection. Gene
      delivery with peptide/DNA complexes was much more effective in rats treated with
      D-galactosamine. However, gene delivery with naked DNA was equally effective in
      normal and damaged livers. Localisation of gene expression showed a scattering of
      positive hepatocytes restricted to the right lateral lobe. CONCLUSIONS:
      Retrograde infusion into the bile duct advances well into the hepatic lobule and
      reveals a remarkable permeability of the canalicular or cholangiole tight
      junctions in normal rats. It is an effective approach for delivering genes to a
      small population (approximately 1%) of hepatocytes.

PMID- 15985563
TI  - Stopping seizure medications in children: when is it safe?

PMID- 15985564
TI  - Welding and Parkinson disease: is there a bond?

PMID- 15985565
TI  - Do we have brain to spare?

PMID- 15985566
TI  - Treatment of carpal tunnel syndrome: is there a role for local corticosteroid
      injection?

PMID- 15985567
TI  - Searching for a relationship between manganese and welding and Parkinson's
      disease.
AB  - Research into the causes of Parkinson disease (PD) has accelerated recently with
      the discovery of novel gene mutations. The majority of PD cases, however, remain
      idiopathic and in those cases environmental causes should be considered. Several
      recent reports have focused on welding and manganese toxicity as potential risk
      factors for parkinsonism and some have even proposed that welding is a risk
      factor for PD. The controversy has stimulated this review, the primary aim of
      which is to critically and objectively examine the evidence or lack of evidence
      for a relationship among welding, manganese, parkinsonism, and PD.

PMID- 15985568
TI  - Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study.
AB  - BACKGROUND: Unsaturated fatty acids are important constituents of neuronal cell
      membranes and have neuroprotective, antioxidant, and anti-inflammatory
      properties. OBJECTIVE: To determine if a high intake of unsaturated fatty acids
      might be associated with a lower risk of Parkinson disease (PD). METHODS: In the
      Rotterdam Study, a prospective population-based cohort study of people ages > or
      =55, the association between intake of unsaturated fatty acids and the risk of
      incident PD was evaluated among 5,289 subjects who were free of dementia and
      parkinsonism and underwent complete dietary assessment at baseline. PD was
      assessed through repeated in-person examination, and the cohort was continuously
      monitored by computer linkage to medical records. The data were analyzed using
      Cox proportional hazards regression models. RESULTS: After a mean follow-up of
      6.0 years, 51 participants with incident PD were identified. Intakes of total
      fat, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs)
      were significantly associated with a lower risk of PD, with an adjusted hazard
      ratio per SD increase of energy-adjusted intake of 0.69 (95% CI 0.52 to 0.91) for
      total fat, of 0.68 (95% CI 0.50 to 0.94) for MUFAs, and 0.66 (95% CI 0.46 to
      0.96) for PUFAs. No associations were found for dietary saturated fat,
      cholesterol, or trans-fat. CONCLUSION: These findings suggest that high intake of
      unsaturated fatty acids might protect against Parkinson disease.

PMID- 15985569
TI  - A new screening tool for cervical dystonia.
AB  - BACKGROUND: Family studies of dystonia may be limited in part by small family
      size and incomplete ascertainment of dystonia in geographically dispersed
      families. Further, prevalence estimates of dystonia are believed to be
      underestimates, as most studies are clinic-based and many individuals do not
      present to a physician or are misdiagnosed. As a low-cost highly sensitive
      screening tool is needed to improve case detection for genetic and epidemiologic
      studies, the authors developed the Beth Israel Dystonia Screen (BIDS), a computer
      assisted telephone interview. OBJECTIVE: To evaluate the validity and utility of
      a computer-assisted telephone interview in screening for cervical dystonia.
      METHODS: The BIDS was administered and videotaped neurologic examinations
      performed on 193 individuals from 16 families with cervical and cranial dystonia.
      With use of a final rating of definite dystonia, as determined by video review of
      a systematic neurologic evaluation, as the gold standard, the predictive value of
      a subset of questions from the BIDS was assessed. RESULTS: A positive response to
      at least two of five screening questions had a sensitivity for cervical dystonia
      of 100% and a specificity of 92%. With use of a positive response to three or
      more questions, definite dystonia was determined with 81% sensitivity and 97%
      specificity. CONCLUSIONS: The Beth Israel Dystonia Screen (BIDS) identifies
      cervical dystonia with excellent sensitivity and specificity in a family-based
      sample. The authors recommend the BIDS for family studies, but cross-validation
      in a population sample is advisable before applying this method to epidemiologic
      studies.

PMID- 15985570
TI  - New and reliable MRI diagnosis for progressive supranuclear palsy.
AB  - OBJECTIVE: To evaluate the area of the midbrain and pons on mid-sagittal MRI in
      patients with progressive supranuclear palsy (PSP), Parkinson disease (PD), and
      multiple-system atrophy of the Parkinson type (MSA-P), compare these appearances
      and values with those of normal control subjects, and establish diagnostic MRI
      criteria for the diagnosis of PSP. METHODS: The authors prospectively studied MRI
      of 21 patients with PSP, 23 patients with PD, 25 patients with MSA-P, and 31 age
      matched normal control subjects. The areas of the midbrain tegmentum and the pons
      were measured on mid-sagittal MRI using the display tools of a workstation. The
      ratio of the area of the midbrain to the area of the pons was also evaluated in
      all subjects. RESULTS: The average midbrain area of the patients with PSP (56.0
      mm2) was significantly smaller than that of the patients with PD (103.0 mm2) and
      MSA-P (97.2 mm2) and that of the age-matched control group (117.7 mm2). The
      values of the area of the midbrain showed no overlap between patients with PSP
      and patients with PD or normal control subjects. However, patients with MSA-P
      showed some overlap of the values of individual areas with values from patients
      with PSP. The ratio of the area of the midbrain to the area of pons in the
      patients with PSP (0.124) was significantly smaller than that in those with PD
      (0.208) and MSA-P (0.266) and in normal control subjects (0.237). Use of the
      ratio allowed differentiation between the PSP group and the MSA-P group.
      CONCLUSION: The area of the midbrain on mid-sagittal MRI can differentiate PSP
      from PD, MSA-P, and normal aging.

PMID- 15985571
TI  - Cerebral MRI findings and cognitive functioning: the Atherosclerosis Risk in
      Communities study.
AB  - OBJECTIVE: To examine the association between prevalent cerebral abnormalities
      identified on MRI and cognitive functioning in a predominantly middle-aged,
      population-based study cohort. METHODS: Cerebral MRI was performed on 1,538
      individuals (aged 55 to 72) from the Atherosclerosis Risk in Communities (ARIC)
      cohort, with no history of stroke or TIA, at study sites in Forsyth County, NC,
      and Jackson, MS. White matter hyperintensities (WMHs), ventricular size, and
      sulcal size were graded by trained neuroradiologists on a semiquantitative, 10
      point scale. Cognitive functioning was assessed using the Delayed Word Recall
      Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT).
      RESULTS: High ventricular grade was independently associated with significantly
      lower scores on the DWRT and DSST and greater risk (odds ratio [OR] 2.32, 95%
      confidence interval [CI] 1.51 to 3.56) of impaired scores (i.e., < or =10th
      percentile) on the DWRT. High sulcal grade was associated with a modest decrement
      in scores on the DWRT. The presence of coexisting high grade WMHs and silent
      infarcts was independently associated with lower scores on all cognitive tests
      and greater risk of impaired functioning on the DSST (OR 2.91, 95% CI: 1.23 to
      6.89) and WFT (OR 2.28, 95% CI 1.03 to 5.08). The presence of two or more high
      grade abnormalities was associated with increased risk of impaired functioning on
      all cognitive tests (DWRT: OR 2.23, 95% CI 1.40 to 3.55; DSST: OR 2.06, 95% CI
      1.13 to 3.76; WFT: OR 2.07, 95% CI 1.23 to 3.49) independent of multiple
      covariates and silent infarcts. CONCLUSION: Common changes in brain morphology
      are associated with diminished cognitive functioning in middle-aged and young
      elderly individuals.

PMID- 15985572
TI  - Hyperventilation-induced nystagmus in vestibular schwannoma.

PMID- 15985573
TI  - Testosterone improves spatial memory in men with Alzheimer disease and mild
      cognitive impairment.
AB  - OBJECTIVE: To determine the efficacy of testosterone (T) supplementation on
      cognition in a sample of men with Alzheimer disease (AD) or mild cognitive
      impairment (MCI). METHODS: Fifteen patients with AD and 17 patients with MCI aged
      63 to 85 years completed a randomized, double-blind, placebo-controlled study.
      Nineteen participants received weekly intramuscular (IM) injections of 100 mg T
      enanthate and 13 participants received weekly injections of placebo (saline) for
      6 weeks. Cognitive evaluations using a battery of neuropsychological tests were
      conducted at baseline, week 3, and week 6 of treatment and again after 6 weeks of
      washout. RESULTS: Peak serum total T levels were raised from baseline an average
      of 295% in the active treatment group. Improvements in spatial memory (p < 0.05)
      and constructional abilities (p < 0.05) and verbal memory were evident in the T
      group. No changes were noted for selective and divided attention or language.
      Prostate specific antigen did not significantly change during this brief
      treatment. CONCLUSION: Testosterone supplementation may benefit selective
      cognitive functions in men with Alzheimer disease and mild cognitive impairment.

PMID- 15985575
TI  - A randomized controlled trial of surgery vs steroid injection for carpal tunnel
      syndrome.
AB  - BACKGROUND: Decompressive surgery and steroid injection are widely used forms of
      treatment for carpal tunnel syndrome (CTS) but there is no consensus on their
      effectiveness in comparison to each other. The authors evaluated the efficacy of
      surgery vs steroid injection in relieving symptoms in patients with CTS. METHODS:
      The authors conducted a randomized, single blind, controlled trial. Fifty
      patients with electrophysiologically confirmed idiopathic CTS were randomized and
      assigned to open carpal tunnel release (25 patients) or to a single injection of
      steroid (25 patients). Patients were followed up at 6 and 20 weeks. The primary
      outcome was symptom relief in terms of the Global Symptom Score (GSS), which
      rates symptoms on a scale of 0 (no symptoms) to 50 (most severe). Nerve
      conduction studies and grip strength measurements were used as secondary outcome
      assessments. RESULTS: At 20 weeks after randomization, patients who underwent
      surgery had greater symptomatic improvement than those who were injected. The
      mean improvement in GSS after 20 weeks was 24.2 (SD 11.0) in the surgery group vs
      8.7 (SD 13.0) in the injection group (p < 0.001); surgical decompression also
      resulted in greater improvement in median nerve distal motor latencies and
      sensory nerve conduction velocity. Mean grip strength in the surgical group was
      reduced by 1.7 kg (SD 5.1) compared with a gain of 2.4 kg (SD 5.5) in the
      injection group. CONCLUSION: Compared with steroid injection, open carpal tunnel
      release resulted in better symptomatic and neurophysiologic outcome but not grip
      strength in patients with idiopathic carpal tunnel syndrome over a 20-week
      period.

PMID- 15985574
TI  - Cognitive differences in dementia patients with autopsy-verified AD, Lewy body
      pathology, or both.
AB  - OBJECTIVE: To examine the neuropsychological profile of dementia patients from a
      community-based autopsy sample of dementia, comparing Alzheimer disease (AD),
      Lewy body pathology (LBP) alone, and LBP with coexistent AD (AD/LBP). METHODS:
      The authors reviewed 135 subjects from a community-based study of dementia for
      whom autopsy and brain tissue was available. Diagnostic groups were determined
      according to standard neuropathologic methods and criteria, and the presence of
      LBs was determined using alpha-synuclein immunostaining. Neuropathologically
      defined diagnostic groups of AD, AD/LBP, and LBP were examined for differences on
      neuropsychological test performance at the time of initial study enrollment.
      RESULTS: There were 48 patients with AD alone, 65 with LB and AD pathology
      (AD/LBP), and 22 with LBP alone (LBP alone). There were no significant
      differences between groups demographically or on performance of enrollment Mini
      Mental State Examination (MMSE) or Dementia Rating Scale (DRS). AD patients
      performed worse than the LBP patients on memory measures (Fuld Object Memory
      Evaluation Delayed Recall, Wechsler Memory Scale Logical Memory Immediate and
      Delayed Recall; p < 0.05) and a naming task (Consortium to Establish a Registry
      for Alzheimer's Disease Naming; p < 0.05). LBP patients were more impaired than
      AD patients on executive function (Trail Making Test Part B; p < 0.05) and
      attention tasks (Wechsler Adult Intelligence Scale-Revised Digit Span; p < 0.05).
      Decline in MMSE and DRS scores over time were greatest in the patients with
      AD/LBP. CONCLUSIONS: In a community-based sample of older, medically complicated
      patients with dementia, there are neuropsychological differences between dementia
      subtypes at the time of diagnosis. In particular, patients with Alzheimer disease
      (AD) alone and AD/Lewy body pathology (LBP) had more severe memory impairment
      than patients with LBP. LBP alone was associated with more severe executive
      dysfunction. Patients with AD/LBP had the most rapid rate of cognitive decline.

PMID- 15985576
TI  - Malignant transformation in polyneuropathy associated with monoclonal gammopathy.
AB  - OBJECTIVE: To assess the frequency of hematologic malignancies at diagnosis and
      to determine the incidence and predictors of malignant transformation during
      follow-up in patients with polyneuropathy associated with monoclonal gammopathy.
      METHODS: Potential predictors of malignant transformation from medical history,
      hematologic, neurologic, and laboratory examination performed each 6 months were
      evaluated by univariable and multivariable Cox proportional hazard analysis.
      RESULTS: Of 193 patients with polyneuropathy associated with monoclonal
      gammopathy, 17 patients had a hematologic malignancy at diagnosis. The incidence
      rate of malignant transformation in 176 patients without a malignancy at
      diagnosis was 2.7/100 patient years. Weight loss, progression of the
      polyneuropathy, unexplained fever or night sweats, and M-protein level were
      independent predictors. CONCLUSIONS: Since hematologic malignancies occur
      frequently in polyneuropathy associated with monoclonal gammopathy, the authors
      suggest that all patients should be screened at diagnosis and subsequently during
      follow-up if malignant transformation is suspected.

PMID- 15985577
TI  - Thermogram of idiopathic segmental anhidrosis.

PMID- 15985578
TI  - MRS of oligodendroglial tumors: correlation with histopathology and genetic
      subtypes.
AB  - BACKGROUND: Oligodendroglial neoplasms with combined loss of chromosomes 1p and
      19q may have a good prognosis and respond to procarbazine-lomustine (CCNU)
      vincristine (PCV) chemotherapy. OBJECTIVE: To determine whether single voxel
      magnetic resonance spectroscopy (SV-MRS) obtained through routine clinical
      practice distinguishes between histopathologic and genetic subtypes of
      oligodendroglial tumors. METHODS: Forty-eight patients with oligodendroglial
      tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular
      genetic analysis to determine allelic imbalance in chromosomes 1p36 and 19q13. SV
      MRS was obtained pretherapy to determine tumor metabolite ratios. RESULTS: Grade
      III oligodendroglial tumors had higher choline (Mann-Whitney; p = 0.002), methyl
      lipid (Mann-Whitney; p = 0.002), and combined methylene lipid and lactate ratios
      (Mann-Whitney; p < 0.001) than grade II tumors. Lactate did not distinguish
      between tumor types (Fisher exact test; p = 0.342) or grade (Fisher exact test; p
      = 0.452). There were no significant associations when tumors were analyzed
      according to histopathology or genetic subtypes. CONCLUSION: As a noninvasive
      diagnostic tool used in routine clinical practice, SV-MRS has the potential
      benefit of determining oligodendroglial tumor grade but not subtypes classified
      by histopathology or molecular genetics. MRS may be useful for determining the
      timing of therapy but is unlikely to predict chemosensitivity.

PMID- 15985579
TI  - CACNA1A mutations causing episodic and progressive ataxia alter channel
      trafficking and kinetics.
AB  - BACKGROUND: CACNA1A encodes CaV2.1, the pore-forming subunit of P/Q-type voltage
      gated calcium channel complexes. Mutations in CACNA1A cause a wide range of
      neurologic disturbances variably associated with cerebellar degeneration.
      Functional studies to date focus on electrophysiologic defects that do not
      adequately explain the phenotypic findings. OBJECTIVE: To investigate whether
      some missense mutations might interfere with protein folding and trafficking,
      eventually leading to protein aggregation and neuronal injury. METHODS: The
      authors studied the functional consequences of two pore missense mutations, C287Y
      and G293R, in two families with EA2, one newly discovered and the other
      previously reported. Both mutations caused episodic and interictal ataxia. The
      biophysical properties of mutant and wild type calcium channels were examined by
      whole-cell patch-clamp recordings in transfected COS-7 cells. The plasma membrane
      targeting was visualized by confocal fluorescence imaging on CaV2.1 tagged with
      green fluorescent protein. RESULTS: The mutant channels exhibited a marked
      reduction in current expression and deficiencies in plasma membrane targeting.
      CONCLUSIONS: In addition to altered channel function, the deficiency in protein
      misfolding and trafficking associated with the C287Y and G293R mutants may
      contribute to the slowly progressive cerebellar ataxia.

PMID- 15985580
TI  - Saccades in children with spina bifida and Chiari type II malformation.
AB  - BACKGROUND: Saccades are essential for optimal visual function. Chiari type II
      malformation (CII) is a congenital anomaly of the cerebellum and brainstem,
      associated with spina bifida. OBJECTIVE: To investigate the effects of CII on
      saccades and correlate saccadic parameters with brain MRI measurements. METHODS:
      Saccades were recorded in 21 participants with CII, aged 8 to 19, using an
      infrared eye tracker. Thirty-nine typically developing children served as
      controls. Participants made saccades to horizontal and vertical target steps.
      Nineteen participants with CII had MRI. Regression analyses were used to
      investigate the effects of spinal lesion level, number of shunt revisions,
      presence of nystagmus, and midsagittal MRI measurements on saccades. RESULTS:
      Saccadic amplitude gains, asymptotic peak velocities, and latencies did not
      differ between the control and CII groups (p > 0.01). No significant differences
      were found between saccadic gains, asymptotic peak velocities or latencies, and
      spinal lesion level, number of shunt revisions, presence of nystagmus, or MRI
      measurements. CONCLUSIONS: Saccades were normal in most participants with Chiari
      II malformation (CII). Neural coding of saccades is robust and is typically not
      affected by the anatomic deformity of CII.

PMID- 15985581
TI  - Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the factors associated with seizures in systemic lupus
      erythematosus (SLE). METHODS: One hundred ninety-five patients with SLE were
      followed at the University of Maryland Lupus Clinics from January 1992 until June
      2004. Neuropsychiatric (NP) manifestations were defined according to the American
      College of Rheumatology nomenclature and case definitions for NP-SLE syndromes,
      and seizures were defined using the International Classification of Epileptic
      Seizures. At the end of the study period, 28 of the 195 (14%) patients with SLE
      had seizures (21 generalized convulsive, 7 partial) during their course of
      disease. Recurrent seizures or epilepsy occurred in 12 of 28 patients (43%). The
      baseline features of those patients with seizures and those without them were
      compared to determine their contribution to the occurrence of isolated seizures
      and epilepsy. RESULTS: Isolated seizures in SLE are common; epilepsy is less
      frequent but nonetheless important. Certain clinical features at baseline were
      independent predictors of seizures including disease activity, in particular
      psychosis, moderate- to high-titer serum anti-cardiolipin and anti-Smith
      antibodies, and damage accrual. Higher disease activity at baseline, concurrent
      multiple NP-SLE manifestations, prior strokes, and male gender were predictive of
      epilepsy. CONCLUSION: The risk of seizure and epilepsy in systemic lupus
      erythematosus (SLE) is increased in those patients with higher disease activity
      at baseline, prior neuropsychiatric SLE disease, and anti-cardiolipin and anti
      Smith antibodies.

PMID- 15985582
TI  - Cognitive and behavioral effects of lamotrigine and topiramate in healthy
      volunteers.
AB  - BACKGROUND: The relative cognitive and behavioral effects of lamotrigine (LTG)
      and topiramate (TPM) are unclear. METHODS: The authors directly compared the
      cognitive and behavioral effects of LTG and TPM in 47 healthy adults using a
      double-blind, randomized crossover design with two 12-week treatment periods.
      During each treatment condition, subjects were titrated to receive either LTG or
      TPM at a target dose of 300 mg/day for each. Neuropsychological evaluation
      included 17 measures yielding 41 variables of cognitive function and subjective
      behavioral effects. Subjects were tested at the end of each antiepileptic drug
      (AED) treatment period and during two drug-free conditions (pretreatment baseline
      and 1 month following final AED withdrawal). RESULTS: Direct comparison of the
      two AEDs revealed significantly better performance on 33 (80%) variables for LTG,
      but none for TPM. Even after adjustment for blood levels, performance was better
      on 19 (46%) variables for LTG, but none for TPM. Differences spanned both
      objective cognitive and subjective behavioral measures. Comparison of TPM to the
      non-drug average revealed significantly better performance for non-drug average
      on 36 (88%) variables, but none for TPM. Comparison of LTG to non-drug average
      revealed better performance on 7 (17%) variables for non-drug average and 4 (10%)
      variables for LTG. CONCLUSIONS: Lamotrigine produces significantly fewer untoward
      cognitive and behavioral effects compared to topiramate (TPM) at the dosages,
      titrations, and timeframes employed in this study. The dosages employed may not
      have been equivalent in efficacy. Future studies are needed to delineate the
      cognitive and behavioral effects of TPM at lower dosages.

PMID- 15985583
TI  - Time to hospital arrival, use of thrombolytics, and in-hospital outcomes in
      ischemic stroke.
AB  - OBJECTIVE: To determine the interval between symptom onset and hospital arrival
      and its relationship to baseline clinical characteristics, use of thrombolysis,
      and in-hospital outcomes in patients with acute ischemic stroke admitted to the
      11 hospitals in the Buffalo metropolitan area and Erie County. METHODS: The
      medical records of 1,590 patients were reviewed to determine the severity of the
      neurologic deficits (NIH Stroke Scale [NIHSS]), in-hospital mortality, favorable
      outcome (modified Rankin Scale score of < or = 2 at discharge), and strata of
      time interval between symptom onset and hospital arrival. RESULTS: The time
      interval between symptom onset and hospital arrival was 0 to 3 hours in 337 (21%)
      patients, 3 to 6 hours in 177 (11%) patients, 6 to 24 hours in 301 (19%)
      patients, > 24 hours in 420 (26%) patients, and undetermined in 355 (22%)
      patients. IV (n = 23) and intra-arterial (n = 4) thrombolysis was used in 27 (8%)
      of the 337 patients that presented within 3 hours of symptom onset. In 1,235
      patients with known time interval between symptom onset and hospital arrival, an
      association (p = 0.008) was observed between strata of increasing time interval
      and higher proportion of favorable outcomes at discharge. The initial NIHSS score
      was higher with decreasing interval between symptom onset and hospital arrival (p
      < 0.0001). CONCLUSIONS: A small proportion of patients who present within 3 hours
      of symptom onset receive thrombolytic therapy. The observation that patients with
      more severe neurologic deficits and subsequently worse in-hospital outcomes
      appear to present early after symptom onset to the hospital may have implications
      for clinical studies.

PMID- 15985584
TI  - Relative elevation in baseline leukocyte count predicts first cerebral
      infarction.
AB  - BACKGROUND: Atherosclerosis is an inflammatory disease, and leukocyte levels are
      associated with future risk of ischemic cardiac disease. OBJECTIVE: To
      investigate the hypothesis that relative elevations in leukocyte count in a
      stroke-free population predict future ischemic stroke (IS). METHODS: A population
      based prospective cohort study was performed in a multiethnic urban population.
      Stroke-free community participants were identified by random-digit dialing.
      Leukocyte levels were measured at enrollment, and participants were followed
      annually for IS, myocardial infarction (MI), and cause-specific mortality. Cox
      proportional hazards regression models were used to calculate hazard ratios (HRs)
      and 95% CIs for IS, MI, and vascular death after adjustment for medical,
      behavioral, and socioeconomic factors. RESULTS: Among 3,103 stroke-free community
      participants (mean age 69.2 +/- 10.3 years) with baseline leukocyte levels
      measured, median follow-up was 5.2 years. After adjusting for stroke risk
      factors, each SD in leukocyte count (1.8 x 10(9) cells/L) was associated with an
      increased risk of IS (HR 1.22, 95% CI 1.05 to 1.42), and IS, MI, or vascular
      death (HR 1.13, 95% CI 1.02 to 1.26). Compared with those in the lowest quartile
      of leukocyte count, those in the highest had an increased risk of IS (adjusted HR
      1.75, 95% CI 1.08 to 2.82). The effect on atherosclerotic and cardioembolic
      stroke was greater than in other stroke subtypes. CONCLUSION: Relative elevations
      in leukocyte count are independently associated with an increased risk of future
      ischemic stroke and other cardiovascular events.

PMID- 15985585
TI  - Drop attacks secondary to superior canal dehiscence syndrome.
AB  - Two patients with unprovoked drop attacks were found to have dehiscence of the
      superior semicircular canal on CT of the temporal bone. Both had conductive
      hearing loss, preservation of stapedius reflex, and abnormal vestibular evoked
      myogenic potentials. Neither had sound- or pressure-induced nystagmus. Repair of
      the dehiscence in one case stopped the drop attacks, supporting a causal
      relationship between the dehiscence and the drop attacks.

PMID- 15985586
TI  - A phenotype without spasticity in sacsin-related ataxia.
AB  - The authors describe two Japanese siblings with autosomal recessive spastic
      ataxia of Charlevoix-Saguenay (ARSACS) without spasticity, usually a core feature
      of this disorder. They had a novel homozygous missense mutation (T987C) of the
      SACS gene, which resulted in a phenylalanine-to-serine substitution at amino acid
      residue 304.

PMID- 15985587
TI  - "Applause sign" helps to discriminate PSP from FTD and PD.
AB  - The "applause sign" is a simple test of motor control that helps to differentiate
      PSP from frontal or striatofrontal degenerative diseases. It was found in 0/39
      controls, 0 of 24 patients with frontotemporal dementia (FTD), 0 of 17 patients
      with Parkinson disease (PD), and 30/42 patients with progressive supranuclear
      palsy (PSP). It discriminated PSP from FTD (p < 0.001) and PD (p < 0.00). The
      "three clap test" correctly identified 81.8% of the patients in the comparison
      PSP and FTD and 75% of the patients in the comparison of PSP and PD.

PMID- 15985588
TI  - Depression is associated with impairment of ADL, not motor function in Parkinson
      disease.
AB  - Depression was diagnosed in 15% of 100 consecutive patients with Parkinson
      disease (PD). Depression was associated with lower cognition, history of
      depression, and a higher Unified Parkinson's Disease Rating Scale score. The
      latter was due to differences in the activities of daily living (ADL) subscale
      (17 +/- 7 vs 12 +/- 6; p = 0.004) rather than the motor subscale (30 +/- 13 vs 26
      +/- 13; p = 0.27). These results suggest that ADL impairment may in part be due
      to depression. Patients with PD with poor function should be closely evaluated
      for depression.

PMID- 15985589
TI  - Four-year outcome after early withdrawal of antiepileptic drugs in childhood
      epilepsy.
AB  - Four-year follow-up of children with epilepsy included in a randomized trial of
      early withdrawal of antiepileptic drugs showed that 51% achieved a terminal
      remission of at least 2 years without medication and 21% with medication; 15% had
      seizures during the fourth year. Early medication withdrawal is not recommended
      as standard practice in children with a rapid response to medication. The authors
      developed a model to predict outcome if withdrawal is considered.

PMID- 15985590
TI  - Disease severity in children and adults with Pompe disease related to age and
      disease duration.
AB  - Information about 255 children and adults with Pompe disease was gathered through
      a questionnaire. Disease severity was associated with disease duration and not
      with age; an early manifestation of the disease implied earlier wheelchair or
      ventilator dependency. The patient group under age 15 included a subgroup with a
      more severe and rapid course of the disease. They require more intensive follow
      up and early intervention, before irreversible damage has occurred.

PMID- 15985591
TI  - Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency.
AB  - Neurologic disease in glutaryl-CoA dehydrogenase (GCDH) deficiency usually
      presents with acute encephalopathic crises before 2 years of age. The authors
      report two previously asymptomatic patients with macrocephaly presenting with
      progressive neurologic deterioration and a severe leukoencephalopathy during
      adolescence or adulthood.

PMID- 15985592
TI  - Opening of the blood-brain barrier preceding cortical edema in a severe attack of
      FHM type II.
AB  - The authors report a patient with familial hemiplegic migraine type II who
      developed a long-lasting attack including fever, right-sided hemiplegia, aphasia,
      and coma. Quantitative analysis of early gadolinium-enhanced MRI revealed a mild
      but significant left-hemispheric blood-brain barrier (BBB) opening limited to the
      cortex and preceding cortical edema. The findings suggest that the delayed
      cortical edema was vasogenic in the severe migraine aura variant of this ATP1A2
      mutation carrier.

PMID- 15985593
TI  - Effect of genetic modifiers on cerebral lesions in Fabry disease.
AB  - Fabry disease is associated with increased risk of premature stroke and
      presumptive ischemic cerebral lesions. In 57 consecutive patients, 35% of whom
      had lesions on brain MRI, the authors found that genotypes of polymorphisms G
      174C of interleukin-6, G894T of endothelial nitric oxide synthase, factor V
      G1691A mutation, and the A-13G and G79A of protein Z were all significantly
      associated with cerebral lesions. These findings suggest that these proteins
      modulate Fabry cerebral vasculopathy.

PMID- 15985594
TI  - Giant arachnoid granulations.

PMID- 15985595
TI  - Spinal fluid 5-methyltetrahydrofolate levels are normal in Rett syndrome.

PMID- 15985596
TI  - Trismus after stroke/TBI: botulinum toxin benefit and use pre-PEG placement.

PMID- 15985597
TI  - Numb ears in resurrection: great auricular nerve injury in hanging attempt.

PMID- 15985598
TI  - Stimulus-induced pathologic laughter due to basilar artery dissection.

PMID- 15985599
TI  - Treatment with botulinum toxin in a patient with myasthenia gravis and cervical
      dystonia.

PMID- 15985600
TI  - Pontine/extrapontine myelinolysis occurring in the setting of an eating disorder.

PMID- 15985601
TI  - Restless legs syndrome in patients with hereditary hemochromatosis.

PMID- 15985602
TI  - Spindle coma from acute midbrain infarction.

PMID- 15985603
TI  - SUNCT syndrome: a possible bilateral case responding to topiramate.

PMID- 15985605
TI  - Progression of dystonia in complex regional pain syndrome.

PMID- 15985606
TI  - A fetal circle of Willis is associated with a decreased deep white matter lesion
      load.

PMID- 15985607
TI  - Clinical characteristics of African Americans vs Caucasian Americans with
      multiple sclerosis.

PMID- 15985608
TI  - Strokes in the subinsular territory: clinical, topographical, and etiological
      patterns.

PMID- 15985609
TI  - The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate
      identification and regulation of cell shape.
AB  - The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes
      including two, pknA and pknB, that are part of an operon encoding genes involved
      in cell shape control and cell wall synthesis. Here we demonstrate that pknA and
      pknB are predominantly expressed during exponential growth, and that
      overexpression of these kinases slows growth and alters cell morphology. We
      determined the preferred substrate motifs of PknA and PknB, and identified three
      in vivo substrates of these kinases: PknB; Wag31, an ortholog of the cell
      division protein DivIVA; and Rv1422, a conserved protein of unknown function.
      Expression of different alleles of wag31 in vivo alters cell shape, in a manner
      dependent on the phosphoacceptor residue in the protein produced. Partial
      depletion of pknA or pknB results in narrow, elongated cells. These data indicate
      that signal transduction mediated by these kinases is a novel mechanism for the
      regulation of cell shape in mycobacteria, one that may be conserved among gram
      positive bacteria.

PMID- 15985610
TI  - PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200,
      to regulate expression of selective interferon-responsive genes.
AB  - PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family
      essential for mammalian transcription and development. Although these complexes
      share eight identical subunits, only PBAF can facilitate transcriptional
      activation by nuclear receptors in vitro. Here we show that these complexes have
      selectivity in mediating transcription of different interferon-responsive genes.
      The selectivity by PBAF requires a novel subunit, BAF200, but not the previously
      described PBAF-specificity subunit, BAF180 (Polybromo). Our study provides in
      vivo evidence that PBAF and BAF regulate expression of distinct genes, and
      suggests that BAF200 plays a key role in PBAF function.

PMID- 15985611
TI  - Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila.
AB  - In Drosophila melanogaster, Dicer-2/R2D2 and Dicer-1 generate small interfering
      RNA (siRNA) and microRNA (miRNA), respectively. Here we identify a novel dsRNA
      binding protein, which we named R3D1-L, that forms a stable complex with Dicer-1
      in vitro and in vivo. While depletion of R3D1-L by RNAi causes accumulation of
      precursor miRNA (pre-miRNA) in S2 cells, recombinant R3D1-L enhances miRNA
      production by Dicer-1 in vitro. Furthermore, R3D1 deficiency causes miRNA
      generating defect and severe sterility in male and female flies. Therefore, R3D1
      L functions in concert with Dicer-1 in miRNA biogenesis and is required for
      reproductive development in Drosophila.

PMID- 15985612
TI  - Differential activation of adenylate cyclase and receptor internalization by
      novel dopamine D1 receptor agonists.
AB  - Structurally dissimilar dopamine D(1) receptor agonists were compared with
      dopamine in their ability to activate adenylate cyclase and to internalize
      hemagglutinin-tagged human D(1) receptors in a stably transfected human embryonic
      kidney cell line. Thirteen dopamine D(1) receptor agonists were selected
      rationally from three different structural classes: rigid fused ring compounds
      [dihydrexidine, dinapsoline, dinoxyline, apomorphine, and (5aR,11bS)
      4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1-ena[c]-phenanthrene
      9,10-diol (A86929)]; isochromans [(1R,3S)-3-(1'adamantyl)-1-aminomethyl-3,4
      dihydo-5,6-dihydroxy-1H-2-benzopyran (A77636) and (1R,3S)-3-phenyl-1-aminomethyl
      3,4-dihydo-5,6-dihydroxy-1H-2-benzopyran (A68930)]; and benzazepines [7,8
      dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF38393), (+/-)-7,8
      dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF77434), 6
      chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      (SKF82958), 3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro
      ]H-3-benzazepine (SKF83959), R(+)-6-chloro-7,8,-dihydroxy-3-methyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzazepine (SKF82957), and R(+)-6-chloro-7,8,-dihydroxy
      1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF81297)]. The working hypothesis
      was that some agonists have differential effects on adenylate cyclase versus
      receptor internalization that could be correlated to the structural class of the
      agonist. First, the affinity for the hemagglutinin-hD(1) receptor and the
      intrinsic activity and potency of adenylate cyclase activation were determined
      for each compound. The internalization time course and internalization efficacy
      were then determined for each agonist. It was surprising that internalization
      efficacy was found to be independent of either agonist structural class or
      affinity. Only agonists that had both high adenylate cyclase functional potency
      and high intrinsic activity caused internalization. In addition, four agonists
      from two structural classes were identified that were capable of fully activating
      adenylate cyclase without eliciting an internalization response. This study
      provides the first extensive characterization of D(1) receptor internalization in
      response to structurally diverse agonists and, at least for the D(1) receptor,
      shows that functional selectivity is not predictable by simple structural
      examination. These data are consistent with the hypothesis that functional
      selectivity reflects subtle ligand-induced conformational changes as opposed to
      simple agonist trafficking among discrete receptor active states.

PMID- 15985613
TI  - SRC family kinase activity is required for murine embryonic stem cell growth and
      differentiation.
AB  - Self-renewal and differentiation of embryonic stem (ES) cells are regulated by
      cytokines and growth factors through tyrosine kinase-dependent signaling
      pathways. In murine ES cells, signals for self-renewal are generated by the
      leukemia inhibitory factor (LIF). LIF and other growth factors are linked to the
      activation of the Src family of cytoplasmic protein-tyrosine kinases (SFKs),
      which consists of eight members having shared structural architecture. In this
      article, we show that murine ES cells express seven SFKs, three of which (Hck,
      Src, and Fyn) exhibit constitutive activity in self-renewing ES cells.
      Differentiation of ES cells to embryoid bodies was associated with rapid
      transcriptional silencing of Hck and Lck and with the loss of the corresponding
      kinase proteins. The expression of other family members remained relatively
      constant, although some loss of Fgr and Lyn proteins was observed during
      differentiation. Like ES cells, embryoid bodies maintained constitutive Src and
      Fyn kinase activity. Partial inhibition of endogenous SFK activity with the ATP
      competitive inhibitors 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine or Src kinase inhibitor-1 induced differentiation of ES cells in the
      presence of LIF. In contrast, suppression of all SFK activity with higher
      concentrations of these inhibitors, or with the more potent compound A-419259
      (Bioorg Med Chem Lett 12:1683-1686, 2002) blocked differentiation in response to
      LIF withdrawal. It is surprising that these inhibitor-treated cells remained
      pluripotent despite the absence of LIF. Our results implicate individual members
      of the Src kinase family in distinct ES cell renewal and differentiation pathways
      and show that small-molecule SFK inhibitors can control ES cell fate.

PMID- 15985614
TI  - G-protein activation by neurokinin-1 receptors is dynamically regulated during
      persistent nociception.
AB  - Previous work has demonstrated that persistent nociception evokes increased
      neurokinin-1 receptor (NK-1) gene expression in the spinal cord dorsal horn of
      the rat within 2 h but has failed to elucidate the relationship between increased
      NK-1 gene expression at later time points and functional regulation of NK-1
      receptor signaling. This study was undertaken to assess changes in NK-1 receptor
      mRNA levels in models of persistent inflammatory hyperalgesia and to relate them
      to changes in the functional coupling of NK-1 receptors to G-protein activity in
      the dorsal horn of the rat. Thus, unilateral intraplantar formalin or complete
      Freund's adjuvant was used to alter mechanical and thermal withdrawal thresholds
      in the inflamed paw. One to 96 h later, NK-1 receptor mRNA levels were quantified
      using solution hybridization-nuclease protection assays. Formalin-evoked
      inflammation produced a 2-fold unilateral increase in NK-1 receptor mRNA levels
      apparent from 2 to 96 h postinjection. Histological sections of the lumbar cord
      from similarly treated rats were used to generate concentration-response curves
      using GTPgammaS35 functional binding assays stimulated by an NK-1 selective
      agonist. Results showed that formalin evoked a transient, bilateral decrease in
      the maximal functional response to 35% of control in the treated side at 24 h
      postinjection and as much as a 10-fold leftward shift in the EC50 of the agonist
      at 12 to 96 h postinjection. These results provide novel evidence that peripheral
      nociceptive activation promotes a central mechanism of hyperalgesia through
      increased functional sensitivity of NK-1 receptors in the spinal cord dorsal
      horn.

PMID- 15985615
TI  - Oxidation of anthracyclines by peroxidase metabolites of salicylic Acid.
AB  - Oxidation of anthracyclines leads to their degradation and inactivation. This
      process is carried out by peroxidases in the presence of a catalytic cofactor, a
      good peroxidase substrate. Here, we investigated the effect of salicylic acid, a
      commonly used anti-inflammatory and analgesic agent, on the peroxidative
      metabolism of anthracyclines. We report that at pharmacologically relevant
      concentrations, salicylic acid stimulates oxidation of daunorubicin and
      doxorubicin by myeloperoxidase and lactoperoxidase systems and that efficacy of
      the process increases markedly on changing the pH from 7 to 5. This pH dependence
      is positively correlated with the ease with which salicylic acid itself undergoes
      metabolic oxidation and involves the neutral form of the acid (pKa = 2.98). When
      salicylic acid reacted with a peroxidase and H2O2 at acid pH (anthracyclines
      omitted), a new metabolite with absorption maximum at 412 nm was formed. This
      metabolite reacted with anthracyclines causing their oxidation. It was
      tentatively assigned to biphenyl quinone, formed by oxidation of biphenol
      produced by dimerization of salicylic acid-derived phenoxyl radicals. The
      formation of this product was inhibited in a concentration-dependent manner by
      the anthracyclines, suggesting their scavenging of the salicylate phenoxyl
      radicals. Altogether, this study demonstrates that oxidation of anthracyclines is
      mediated by peroxidase metabolites of salicylic acid, such as phenoxyl radicals
      and the biphenol quinone. Given that cancer patients undergoing anthracycline
      chemotherapy may be administered salicylic acid-based drugs to control pain and
      fever, our results suggest that liberated salicylic acid could interfere with
      anticancer and/or cardiotoxic actions of the anthracyclines.

PMID- 15985616
TI  - Mechanisms underlying capsaicin-stimulated secretion in the stomach: comparison
      with mucosal acidification.
AB  - The effects of capsaicin and mucosal acidification on gastric HCO3(-) secretion
      were compared in wild-type and prostacyclin (PGI2) IP receptor or prostaglandin E
      receptor EP1 or EP3 knockout C57BL/6 mice as well as rats. Under urethane
      anesthesia, the stomach was mounted on an ex vivo chamber, perfused with saline,
      and the secretion of HCO3(-) was measured at pH 7.0 using the pH-stat method.
      Capsaicin or 200 mM HCl was applied to the chamber for 10 min. Capsaicin
      increased the secretion of HCO3(-) in rats and wild-type mice, the response at
      0.3 mg/ml being equivalent to that induced by acidification. This effect of
      capsaicin in rats was abolished by ablation of capsaicin-sensitive afferent
      neurons and attenuated by indomethacin, N(G)-nitro-L-arginine methylester (L
      NAME), and capsazepine [transient receptor potential vanilloid type 1 (TRPV1)
      antagonist] but not FR172357 [3-bromo-8-[2,6-dichloro-3-[N[(E)-4-(N,N
      dimethylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-metylimidazo[1,2
      a]pyridine; bradykinin B2 antagonist] or the EP1 antagonist. The acid-induced
      HCO3(-) secretion was attenuated by indomethacin, L-NAME, the EP1 antagonist, and
      sensory deafferentation, but not affected by capsazepine or FR172357.
      Prostaglandin E2 (PGE2), NOR-3 [(+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexeneamine] (NO donor), and bradykinin stimulated the secretion of HCO3(-), and
      the effect of bradykinin was blocked by indomethacin and L-NAME as well as
      FR172357. The stimulatory effect of capsaicin disappeared in IP (-/-) mice,
      whereas that of acidification disappeared in EP1 (-/-) mice. Intragastric
      application of capsaicin increased mucosal PGI2 but not PGE2 levels in the rat
      stomach. These results suggested that both capsaicin and acid increase gastric
      HCO3(-) secretion via a common pathway, involving PG and NO as well as capsaicin
      sensitive afferent neurons, yet their responses differ concerning TRPV1 or
      prostanoid receptor dependence.

PMID- 15985617
TI  - Proapoptotic effect on normal and tumor intestinal cells of cytostatic drugs with
      enterohepatic organotropism.
AB  - The proapoptotic effect of cisplatin bile acid derivatives Bamet-R2 [cis
      diamminechloro-cholylglycinate-platinum(II)] and Bamet-UD2 [cis-diammine
      bisursodeoxycholate-platinum(II)], developed to treat liver and intestinal
      tumors, was investigated in vitro using human enterohepatic cells HepG2
      (hepatoblastoma), LS 174T (colon adenocarcinoma), and its cisplatin-resistant
      subline LS 174T/R. Uptake by wild-type tumor cells was higher for Bamets than for
      cisplatin. In LS 174T/R cells, copper transporter-1 was down-regulated and
      multidrug resistance-associated protein-2 was up-regulated. Consequently, uptake
      and efflux of cisplatin, but not those of Bamets, were reduced and increased,
      respectively. The degree of necrosis (lactate dehydrogenase release) induced by
      these three drugs was small and similar in all cell types. In contrast,
      proapoptotic effect (caspase-3 activity and DNA fragmentation) was Bamet-UD2 >
      cisplatin > Bamet-R2 in HepG2 and LS 174T cells, but Bamet-UD2 > Bamet-R2 >>
      cisplatin in LS 174T/R cells. This effect was consistent with the ability of
      these compounds to form DNA-adducts (DNA-platination, changes in the DNA melting
      temperature, and MspI-induced restriction sequence cleavage). Oral administration
      of Bamet-UD2 to mice induced mild apoptosis in the small intestine (ileum >
      duodenum), which was not severe enough to modify its structure or function as
      determined by water absorption and glycocholic acid uptake by in situ perfused
      ileum. These results indicate that Bamet-UD2 overcomes the resistance to
      cisplatin when this is due in part to enhanced ability of intestinal tumors to
      reduce intracellular cisplatin contents. Moreover, its strong proapoptotic versus
      its weak pronecrotic effect together with its mild effect on normal tissues,
      including intestinal mucosa, may account for the high antitumor activity of Bamet
      UD2 together with its very low toxicity.

PMID- 15985618
TI  - Metabolic cardioprotection by pyruvate: recent progress.
AB  - Pyruvate, a natural metabolic fuel and antioxidant in myocardium and other
      tissues, exerts a variety of cardioprotective actions when provided at
      supraphysiological concentrations. Pyruvate increases cardiac contractile
      performance and myocardial energy state, bolsters endogenous antioxidant systems,
      and protects myocardium from ischemia-reperfusion injury and oxidant stress. This
      article reviews and discusses basic and clinically oriented research conducted
      over the last several years that has yielded fundamental information on
      pyruvate's inotropic and cardioprotective mechanisms. Particular attention is
      placed on pyruvate's enhancement of sarcoplasmic reticular Ca2+ transport, its
      antioxidant properties, and its ability to mitigate reversible and irreversible
      myocardial injury. These research efforts are establishing the essential
      foundation for clinical application of pyruvate therapy in numerous settings
      including cardiopulmonary bypass surgery, cardiopulmonary resuscitation,
      myocardial stunning, and cardiac failure.

PMID- 15985619
TI  - Trienzyme extraction in combination with microbiologic assay in food folate
      analysis: an updated review.
AB  - For decades, the traditional food folate extraction method involved two steps
      including heat treatment, to release folate from its binding proteins, and folate
      conjugase treatment, to hydrolyze polyglutamyl folate to monoglutamyl folate.
      However, a trienzyme-extraction method of food folate was developed in the mid
      1990s. This method involves the use of alpha-amylase, protease, and folate
      conjugase and allows for a more complete extraction of folate trapped in
      carbohydrate or protein matrices in food than the traditional method. In the last
      several years, this extraction method became widely used. However, the method is
      not uniform among various investigators, and it may be difficult for a new
      investigator to select the most suitable method in his or her laboratory.
      Therefore, in the review presented here, we summarize a variety of trienzyme
      extraction procedures that were used by various researchers and offer a
      recommended procedure for food folate extraction. It is our hope that the wide
      use of an appropriate procedure of the trienzyme-extraction method, in
      combination with a reasonable detection method, help in establishing accurate and
      reliable food-folate tables and that this, in turn, makes it possible to
      accurately assess folate intake in the general population.

PMID- 15985620
TI  - Target size analysis by radiation inactivation: the use of free radical
      scavengers.
AB  - Several model systems were employed to assess indirect effects that occur in the
      process of using radiation inactivation analysis to determine protein target
      sizes. In the absence of free radical scavengers, such as mannitol and benzoic
      acid, protein functional unit sizes can be drastically overestimated. In the case
      of glutamate dehydrogenase, inclusion of free radical scavengers reduced the
      apparent target size from that of a hexamer to that of a trimer based on enzyme
      activity determinations. For glucose-6-phosphate dehydrogenase, the apparent
      target size was reduced from a dimer to a monomer. The target sizes for both
      glutamate dehydrogenase and glucose-6-phosphate dehydrogenase in the presence of
      free radical scavengers corresponded to subunit sizes when determinations of
      protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or
      immunoblotting were done rather than enzyme activity. The free radical scavengers
      appear to compete with proteins for damage by secondary radiation products, since
      irradiation of these compounds can result in production of inhibitory species.
      Addition of benzoic acid/mannitol to samples undergoing irradiation was more
      effective in eliminating secondary damage than were 11 other potential free
      radical scavenging systems. Addition of a free radical scavenging system enables
      more accurate functional unit size determinations to be made using radiation
      inactivation analysis.

PMID- 15985621
TI  - Differential response to DNA damage may explain different cancer susceptibility
      between small and large intestine.
AB  - Although large intestine (LI) cancer is the second-leading cause of cancer
      related deaths in the United States, small intestine (SI) cancer is relatively
      rare. Because oxidative DNA damage is one possible initiator of tumorigenesis, we
      investigated if the SI is protected against cancer because of a more appropriate
      response to oxidative DNA damage compared with the LI. Sixty rats were allocated
      to three treatment groups: 3% dextran sodium sulfate (DSS, a DNA-oxidizing agent)
      for 48 hrs, withdrawal (DSS for 48 hrs + DSS withdrawal for 48 hrs), or control
      (no DSS). The SI, compared with the LI, showed greater oxidative DNA damage (P <
      0.001) as determined using a quantitative immunohistochemical analysis of 8
      oxodeoxyguanosine (8-oxodG). The response to the DNA adducts in the SI was
      greater than in the LI. The increase of TdT-mediated dUTP-biotin nick end
      labeling (TUNEL)-positive apoptosis after DSS treatment was greater in the SI
      compared with the LI (P < 0.001), and there was a positive correlation (P =
      0.031) between DNA damage and apoptosis in the SI. Morphologically, DSS caused an
      extensive loss of crypt structure shown in lower crypt height (P = 0.006) and the
      number of intact crypts (P = 0.0001) in the LI, but not in the SI. These data
      suggest that the SI may be more protected against cancer by having a more dynamic
      response to oxidative damage that maintains crypt morphology, whereas the
      response of the LI makes it more susceptible to loss of crypt architecture. These
      differential responses to oxidative DNA damage may contribute to the difference
      in cancer susceptibility between these two anatomic sites of the intestine.

PMID- 15985622
TI  - Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female
      golden Syrian hamsters.
AB  - A study was conducted in hamsters to determine if group B soyasaponins improve
      plasma cholesterol status by increasing the excretion of fecal bile acids and
      neutral sterols, to identify group B soyasaponin metabolites, and to investigate
      the relationship between a fecal group B soyasaponin metabolite and plasma
      lipids. Twenty female golden Syrian hamsters, 11-12 weeks old and 85-125 g, were
      randomly assigned to a control diet or a similar diet containing group B
      soyasaponins (containing no isoflavones), 2.2 mmol/kg, for 4 weeks. Hamsters fed
      group B soyasaponins had significantly lower plasma total cholesterol (by 20%),
      non-high-density lipoprotein (HDL) cholesterol (by 33%), and triglycerides (by
      18%) compared with those fed casein (P < 0.05). The ratio of total cholesterol to
      HDL cholesterol was significantly lower (by 13%) in hamsters fed group B
      soyasaponins than in those fed casein (P < 0.05). The excretion of fecal bile
      acids and neutral sterols was significantly greater (by 105% and 85%,
      respectively) in soyasaponin-fed hamsters compared with those fed casein (P <
      0.05). Compared with casein, group B soyasaponins lowered plasma total
      cholesterol levels and non-HDL cholesterol levels by a mechanism involving
      greater excretion of fecal bile acids and neutral sterols. Hamsters fed group B
      soyasaponins statistically clustered into two fecal soyasaponin metabolite
      excretion phenotypes: high excreters (n = 3) and low excreters (n = 7). When high
      and low producers of this soyasaponin metabolite were compared for plasma
      cholesterol status, the high producers showed a significantly lower total
      cholesterol-to-HDL-cholesterol ratio compared with the low producers (1.38 +/-
      0.7 vs. 1.59 +/- 0.13; P < 0.03). Greater production of group B soyasaponin
      metabolite in hamsters was associated with better plasma cholesterol status,
      suggesting that gut microbial variation in soyasaponin metabolism may influence
      the health effects of group B soyasaponins.

PMID- 15985623
TI  - Androgen- and estrogen-dependent regulation of insulin-degrading enzyme in
      subcellular fractions of rat prostate and uterus.
AB  - Innumerous data support the fact that insulin-degrading enzyme (IDE) is the
      primary enzymatic mechanism for initiating and controlling cellular insulin
      degradation. Nevertheless, insulin degradation is unlikely to be the only
      cellular function of IDE, because it appears that some cellular effects of
      insulin are mediated by IDE as a regulatory protein. Insulin-degrading enzyme
      shows a significant correlation with various cellular functions, such as cellular
      growth and differentiation, and the expression of IDE is developmentally
      regulated. Besides insulin, other substrates are also degraded by IDE, including
      various growth-promoting peptides. It has also been shown that IDE enhances the
      binding of androgen to DNA in the nuclear compartment. It is also known that the
      androgen hormones have a stimulatory effect on prostate growth, and that
      estradiol stimulates uterine growth. To establish whether IDE is regulated by a
      cellular prostate/uterine growth stimulus, the present study assessed whether IDE
      was modified in quantity and activity during proliferative conditions (castration
      + testosterone in the male rat, or castration + estradiol or the proestrus phase
      of the estrous cycle in the female rat) and autolysis (castration or the
      metestrus phase of the estrous cycle) using cytosolic and nuclear fractions of
      rat prostate and cytosolic fractions of rat uterus. The activity and amount of
      IDE decreased in the cytosolic fraction with castration and during metestrus, and
      increased with testosterone or estradiol treatment and during proestrus. In the
      nuclear fraction, the quantity of the IDE followed the same pattern observed in
      the cytosolic fraction, although without degradative activity. The data presented
      here suggest that IDE may participate in prostatic and uterine growth and that
      the testosterone or estradiol and/or prostate and uterus insulin-like growth
      factors may be important factors for the expression and regulation of IDE in the
      prostate and uterus.

PMID- 15985624
TI  - The role of interferon-alpha in a successful murine tumor therapy.
AB  - Combination therapy using reovirus type 3 and the chemo-therapeutic agent 1,3
      bis(2-chloroethyl)-1-nitrosourea (BCNU) is sufficient to cure approximately 80%
      of EL-4 lymphoma tumor-bearing BD2F1 male mice. Cured animals can be challenged
      with the EL-4 tumor, in the absence of the therapy, to yield 100% survival,
      whereas those challenged with heterologous tumor produce 0% survival. These
      results strongly suggest that a host-immune response is responsible for the
      observed therapeutic effect. Reovirus, a double-stranded RNA virus, is an
      efficient inducer of type I interferon. In an effort to determine the role of
      virus in this therapy, we substituted interferon-alpha (IFN-alpha) for reovirus
      in the therapy. Doses of IFN-alpha from 1000-10,000 U were capable of replacing
      reovirus to produce cure rates similar to reovirus. Spleen cells isolated from
      therapy-treated animals demonstrated high levels of cytotoxicity against the
      natural killer cell-sensitive cell line YAC-1, but not against EL-4 tumor. In
      vitro stimulation of isolated spleen cells by IFN-alpha resulted in a high level
      of natural killer cell activity, but no cytotoxicity against the EL-4 tumor. A
      significant antiproliferative effect against the EL-4 tumor in cell culture was
      demonstrated by IFN-alpha. Finally, therapy-treated, tumor-bearing mice that were
      injected with anti-IFN-alpha + -beta antibodies had similar survival levels as
      control mice, indicating that other cytokines might also play a role in promoting
      tumor killing. These investigations suggest that IFN-alpha may be a mediator of
      antitumor activity in the reovirus therapy system.

PMID- 15985625
TI  - Culture supernatant of Lactobacillus acidophilus stimulates proliferation of
      embryonic cells.
AB  - Our previous report showed that supernatants of Lactobacillus acidophilus (LS)
      cultures possessed chemotactic and angiogenic properties. Specifically, LS
      stimulated gene expression and the secretion of tumor necrosis factor-alpha (TNF
      alpha), the proliferation of immune cells in vitro, and blood vessel formation.
      Chemotaxis and proliferation of inflammatory cells in vivo were also stimulated
      by LS. In the current study, we hypothesized that LS stimulates the growth and
      development of other rapidly dividing cells, including embryonic cells. The
      stimulatory effects of LS on a neuroblastoma cell line (Neuro-2a), chicken
      embryos, and bovine embryos were examined. The addition of LS to Neuro-2a
      cultures caused a proliferation of cells in a concentration-dependent manner.
      Pretreatment of LS at 56 degrees C for 30 mins did not affect its stimulatory
      activity. The administration of LS to the chorioallantoic membrane (CAM) of
      chicken-embryonated eggs for 1-2 days resulted in extensive thickening of the
      membrane. The thickening was due to the influx and proliferation of fibroblasts
      and inflammatory cells, the accumulation of loose connective tissue composed
      primarily of mucopolysaccharides, and/or the formation of blood vessels.
      Stimulatory effects of LS on bovine embryos were also observed. The treatment
      with LS significantly promoted the development of zygotes to the four-cell stage
      and from the four-cell stage to blastocysts. These results have confirmed our
      hypothesis that LS exerts a stimulatory effect on the cells of embryonic stages
      including neuroblastoma cells, the CAM of chicken embryos, and bovine embryos
      from zygotes to blastocysts.

PMID- 15985626
TI  - Suppression of generalized seizures activity by intrathalamic 2-chloroadenosine
      application.
AB  - In the present study, we investigated the effects of micro-injecting 2
      chloroadenosine (2-CADO; an adenosine receptor agonist) into the thalamus alone
      and with theophylline (a nonspecific adenosine receptor antagonist) pretreatment
      on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in male Wistar albino
      rats. Following intrathalamic 2-CADO injection alone or theophylline
      pretreatment, 50 mg kg(-1) PTZ was given ip after 1 and 24 hrs. The duration of
      epileptic seizure activity was recorded by cortical electroencephalogram (EEG),
      and seizure severity was behaviorally scored. Intrathalamic 2-CADO administration
      induced significant decreases in both seizure duration and seizure severity
      scores at 1 and 24 hrs, but the effects were more abundant on the seizures
      induced after 24 hrs. On the other hand, pretreatment with theophylline prevented
      the inhibitor effect of 2-CADO on seizure activity and increased both seizure
      duration and seizure scores. Present results suggest that the activation of
      adenosine receptors in the thalamus may represent another
      anticonvulsant/modulatory site of adenosine action during the course of the PTZ
      induced generalized tonic-clonic seizures and provide additional data for the
      involvement of the adenosinergic system in the generalized seizures model.

PMID- 15985627
TI  - A guide to issues in microarray analysis: application to endometrial biology.
AB  - Within the last decade, the development of DNA microarray technology has enabled
      the simultaneous measurement of thousands of gene transcripts in a biological
      sample. Conducting a microarray study is a multi-step process; starting with a
      well-defined biological question, moving through experimental design, target RNA
      preparation, microarray hybridisation, image acquisition and data analysis-
      finishing with a biological interpretation requiring further study. Advances
      continue to be made in microarray quality and methods of statistical analysis,
      improving the reliability and therefore appeal of microarray analysis for a wide
      range of biological questions. The purpose of this review is to provide both an
      introduction to microarray methodology, as well as a practical guide to the use
      of microarrays for gene expression analysis, using endometrial biology as an
      example of the applications of this technology. While recommendations are based
      on previous experience in our laboratory, this review also summarises the methods
      currently considered to be best practice in the field.

PMID- 15985628
TI  - FSH and testosterone signaling in Sertoli cells.
AB  - Testosterone and follicle-stimulating hormone (FSH) are required to obtain full
      reproductive potential. In the testis, somatic Sertoli cells transduce signals
      from testosterone and FSH into the production of factors that are required by
      germ cells as they mature into spermatozoa. Recent advances in identifying new
      signaling pathways that are regulated by FSH and testosterone have allowed for
      refinement in the understanding of the independent, overlapping and synergistic
      actions of these hormones. In this review, we discuss the signaling pathways that
      are regulated by FSH and testosterone as well as the resulting metabolic and gene
      expression changes that occur as related to Sertoli cell proliferation,
      differentiation and the support of spermatogenesis.

PMID- 15985629
TI  - The capability of reprogramming the male chromatin after fertilization is
      dependent on the quality of oocyte maturation.
AB  - The present experiments compared the ability of pig oocytes matured either in
      vivo or in vitro to structurally reorganize the penetrated sperm chromatin into
      male pronucleus (PN) and to carry out, in parallel, the epigenetic processes of
      global chromatin methylation and acetylation, 12-14 h after in vitro
      fertilization (IVF). In addition, PN distribution of histone deacetylase (HDAC),
      a major enzyme interfacing DNA methylation and histone acetylation, was
      investigated. The ability of the oocyte to operate an efficient block to
      polyspermy was markedly affected by maturation. The monospermic fertilization
      rate was significantly higher for in vivo than for in vitro matured (IVM) oocytes
      (P < 0.01) which, furthermore, showed a reduced ability to transform the
      chromatin of penetrated sperm into male PN (P < 0.01). Indirect
      immunofluorescence analysis of global DNA methylation, histone acetylation and
      HDAC distribution (HDAC-1, -2 and -3), carried out in monospermic zygotes that
      reached the late PN stage, showed that IVM oocytes also had a reduced epigenetic
      competence. In fact, while in about 80% of in vivo matured and IVF oocytes the
      male PN underwent a process of active demethylation and showed a condition of
      histone H4 hyperacetylation, only 40% of IVM/IVF zygotes displayed a similar PN
      remodelling asymmetry. Oocytes that carried out the first part of maturation in
      vivo (up to germinal vesicle breakdown; GVBD) and then completed the process in
      vitro, displayed the same PN asymmetry as oocytes matured entirely in vivo. A
      crucial role of HDAC in the establishment of PN acetylation asymmetry seems to be
      confirmed by the use of HDAC inhibitors as well as by the abnormal distribution
      of the enzyme between the two PN in IVM zygotes. Collectively, these data
      demonstrated that some pig IVM oocytes fail to acquire full remodelling
      competence which is independent from their ooplasmic ability to morphologically
      reorganize the sperm nucleus into PN.

PMID- 15985630
TI  - Mitogen-activated protein kinase (MAPK) blockade of bovine preimplantation
      embryogenesis requires inhibition of both p38 and extracellular signal-regulated
      kinase (ERK) pathways.
AB  - Blastocyst formation, as a critical period during development, is an effective
      indicator of embryonic health and reproductive efficiency. Out of a number of
      mechanisms underlying blastocyst formation, highly conserved mitogen-activated
      protein kinase (MAPK) signaling has emerged as a major mechanism involved in
      regulating murine preimplantation embryo development. The objective of our study
      was to ascertain the role of MAPK signaling in regulating bovine development to
      the blastocyst stage. Using reverse transcriptase PCR and immunohistochemical
      staining procedures we have demonstrated that mRNA transcripts and polypeptides
      encoding p38 MAPK pathway constituents are detectable in preimplantation bovine
      embryos from the one-cell to the blastocyst stage. Further, the effects on bovine
      embryo development following inhibition of p38 alpha/beta and extracellular
      signal-regulated kinase (ERK) signaling by treatment with SB220025 and U0126,
      respectively, were investigated. Eight-cell bovine embryos (50 per group; three
      replicates) were placed into treatments consisting of synthetic oviductal fluid
      (SOF) medium: SOF + SB202474 (inactive analogue), SOF + SB220025, SOF + U0124
      (inactive analogue), SOF + U0126, and SOF + SB220025 + U0126. Inhibition of p38
      MAPK or ERK signaling individually did not affect development to the blastocyst
      stage. However, when both pathways were blocked simultaneously there was a
      significant reduction (P < 0.05) in blastocyst formation, cell number and
      immunofluorescence of phosphorylated downstream pathway constituents. We have
      determined that, in variance to what was observed during murine preimplantation
      development, bovine early embryos progress at normal frequencies to the
      blastocyst stage in the presence of p38 MAPK inhibitors.

PMID- 15985631
TI  - The genetic heterozygosity and fitness of tetraploid embryos and embryonic stem
      cells are crucial parameters influencing survival of mice derived from embryonic
      stem cells by tetraploid embryo aggregation.
AB  - The aim of this paper was to determine whether the genetic background of
      tetraploid embryos contributed to the survival of mice derived from embryonic
      stem (ES) cells by tetraploid embryo complementation. Twenty-five newborns were
      produced by aggregation of hybrid ES cells and tetraploid embryos with different
      genetic backgrounds. These newborns were entirely derived from ES cells judged by
      microsatellite DNA (A specific sequence of DNA bases or nucleotides that contains
      mono, di, tri or tetra repeats) and coat colour phenotype and germline
      transmission. Fifteen survived to adulthood while seven died of respiratory
      failure. All newborns were derived from outbred or hybrid tetraploid aggregates
      and no newborns were from the inbreds. Our results demonstrate that the genetic
      heterozygosity, fitness of tetraploid embryos and fitness of ES cells are crucial
      parameters influencing survival of mice derived from ES cells by tetraploid
      embryo aggregation. In addition, this method represents a simple and efficient
      procedure for immediate generation of targeted mouse mutants from genetically
      modified ES cell clones, in contrast to the standard protocol, which involves the
      production of chimeras and several breeding steps.

PMID- 15985632
TI  - Cytoskeleton localization in the sperm head prior to fertilization.
AB  - Three major cytoskeletal proteins, actin, tubulin and spectrin, are present in
      the head of mammalian spermatozoa. Although cytoskeletal proteins are implicated
      in the regulation of capacitation and the acrosome reaction (AR), their exact
      role remains poorly understood. The aim of this study was to compare the
      distribution of the sperm head cytoskeleton before and after the AR in
      spermatozoa representing a range of acrosome size and shape. Spermatozoa from the
      human and three rodents (rat, hamster and grey squirrel) were fixed before and
      after the AR in appropriate medium in vitro. Indirect immunofluorescent
      localization of cytoskeletal proteins was undertaken with antibodies recognizing
      actin, spectrin and alpha-tubulin. Preparations were counterstained with
      propidium iodide and examined by epifluorescent and confocal microscopy. Our
      results clearly demonstrated changes in localization of cytoskeleton during the
      AR, mainly in the apical acrosome with further changes to the equatorial segment
      and post-acrosomal regions. The pattern of cytoskeletal proteins in the sperm
      head of all the species was similar in respect to various sub-compartments. These
      observations indicated that the sperm head cortical cytoskeleton exhibits
      significant changes during the AR and, therefore, support the image of
      cytoskeletal proteins as highly dynamic structures participating actively in
      processes prior to fertilization.

PMID- 15985633
TI  - Regulation of apoptosis in the atresia of dominant bovine follicles of the first
      follicular wave following ovulation.
AB  - During atresia of bovine follicles, granulosa cells are lost through the
      controlled form of cell death, apoptosis. The purpose of this study was to
      characterize the regulation of apoptotic death of granulosa cells in dominant
      bovine follicles during the first wave of follicular development. Dominant
      follicles were collected from Holstein heifers on days 4, 6 or 8 of the first
      follicular wave (n = 5/day). Regulation of apoptosis in granulosa cells was
      examined by annexin V and propidium iodide staining; measurement of relative
      levels of mRNA encoding Bcl-2, Bcl-xL and Bax; and activity of caspase-3, -8 and 
      9. Steady-state levels of mRNA encoding four oxidative stress-response proteins
      were determined. Compared with day 4, the incidence of apoptotic and nonviable
      granulosa cells tended to increase on day 6, and numbers of nonviable cells were
      higher on day 8. The ratios of relative levels of mRNA encoding Bcl-2 to Bax and
      Bcl-xL to Bax were higher on day 6 than days 4 and 8. Activity of caspases-3 and 
      9 in granulosa cells did not change among the 3 days, while caspase-8 activity
      decreased on day 8 compared with days 4 and 6. Amounts of GSHPx, MnSOD and
      Cu/ZnSOD mRNA in granulosa cells were higher on day 8 than day 6. In theca
      interna, amounts of Cu/ZnSOD mRNA decreased between days 4 and 6. From the
      decreased production of estradiol and increased numbers of apoptotic and
      nonviable granulosa cells, we conclude that atresia of the dominant follicle is
      initiated between days 4 and 6 of the first follicular wave. However, apoptosis
      of granulosa cells does not appear to be initiated by changes in expression of
      oxidative stress-response proteins.

PMID- 15985634
TI  - The effect of human chorionic gonadotrophin on the expression of progesterone
      receptors in human luteal cells in vivo and in vitro.
AB  - The human corpus luteum expresses genomic progesterone receptors (PRs) suggesting
      that progesterone may have an autocrine or paracrine role in luteal function. We
      hypothesised that the reduction in luteal PR reported in the late-luteal phase
      augmented progesterone withdrawal and had a role in luteolysis. We therefore
      tested the hypothesis that luteal rescue with human chorionic gonadotrophin (hCG)
      would maintain PR expression. PR was immunolocalised to different cell types in
      human corpora lutea (n = 35) from different stages of the luteal phase and after
      luteal rescue with exogenous hCG. There was no change in the staining intensity
      of theca-lutein cell or stromal cell PR throughout the luteal phase or after
      luteal rescue. In the late-luteal phase, granulosa-lutein cell PR immunostaining
      was reduced (P < 0.05) but the trend to reduction was also seen after luteal
      rescue with hCG (P = 0.055). To further investigate the effect of hCG on
      granulosa-lutein cell PR expression, an in vitro model system of cultured human
      luteinised granulosa cells was studied. Cells were cultured for 12-13 days
      exposed to different patterns of hCG and aminoglutethamide to manipulate
      progesterone secretion (P < 0.0001). Expression of PR A/B and PR B isoforms was
      examined by quantitative real-time RT-PCR. PR A/B mRNA was lower (P < 0.05) after
      11-13 days of culture than after 7 days of culture. This reduction could not be
      prevented by hCG in the presence (P < 0.05) or absence (P < 0.05) of stimulated
      progesterone secretion. The expression of PR B mRNA showed a similar pattern (P =
      0.054). Simulated early pregnancy in vivo and hCG treatment of luteinised
      granulosa cells in vitro did not appear to prevent the down-regulation of PR seen
      during luteolysis.

PMID- 15985635
TI  - Cytotrophoblast differentiation in the first trimester of pregnancy: evidence for
      separate progenitors of extravillous trophoblasts and syncytiotrophoblast.
AB  - It is commonly accepted that a single pool of villous cytotrophoblasts are
      precursors of both syncytiotrophoblast and extravillous trophoblasts during the
      first trimester. Here we present evidence that these two trophoblast
      subpopulations arise from separate progenitors that have different survival
      characteristics when studied in villous explant cultures. Dual staining with
      chloromethylfluorescin diacetate and ethidium bromide revealed degeneration of
      the syncytiotrophoblast by non-apoptotic mechanisms within 4 h of culture. The
      syncytiotrophoblast had regenerated within 48 h but at this point the vast
      majority of the cytotrophoblast and cells of the mesenchymal core were dead.
      Despite this extensive cytotrophoblast death, explants are able to produce
      extravillous trophoblast outgrowth for up to 3 weeks in culture. We believe that
      the villous cytotrophoblasts in the tips of anchoring villi are resistant to the
      factors that cause the death of the majority of villous cytotrophoblasts in
      culture. We speculate that as early as 8 weeks of gestation there are two
      separate villous cytotrophoblast populations, one committed to differentiate into
      syncytiotrophoblast and the second committed to the extravillous differentiation
      pathway.

PMID- 15985636
TI  - Effect of LH on prostaglandin F2alpha and prostaglandin E2 secretion by cultured
      porcine endometrial cells.
AB  - LH appears to be a potent stimulator of the release of endometrial prostaglandins
      (PGs) in the pig. The aim of the present studies was to examine the effect of LH
      on PGF2alpha and PGE2 secretion by cultured porcine endometrial cells on days 10
      12 and 14-16 of the oestrous cycle and to compare its action with oxytocin. A
      time-dependent effect of LH (10 ng/ml) on PGF2alpha release from luminal
      epithelial and stromal cells on days 10-12 was observed (experiment 1). The
      highest increase in PGF2alpha secretion in response to LH was detected in stromal
      cells after 6 h of incubation (P < 0.001). Epithelial cells responded to LH after
      a longer exposure time (P < 0.01). A concentration-dependent effect of LH (0.1
      100 ng/ml) on PGF2alpha release from stromal cells was examined after 6 h and
      from epithelial cells after 12 h (experiment 2). Effective concentrations of LH
      were 10 and 100 ng/ml. LH (10 ng/ml) and oxytocin (100 nmol/l) affected PGF2alpha
      and PGE2 secretion from endometrial cells on days 10-12 and 14-16 of the oestrous
      cycle (experiment 3). LH stimulated PGF2alpha secretion from both cell types and
      its action was more potent on days 10-12. LH induced PGE2 release, especially in
      epithelial cells on days 14-16. A stimulatory effect of oxytocin on PGF2alpha was
      confirmed in stromal cells, but this hormone was also shown to enhance PGE2
      output. These results indicated that LH, like oxytocin, a very effective
      stimulator of PGF2alpha release, could play an important role in the induction of
      luteolysis.

PMID- 15985637
TI  - Pregnancy-induced decrease in the relaxant effect of terbutaline in the late
      pregnant rat myometrium: role of G-protein activation and progesterone.
AB  - The effectiveness of beta2-agonists in preterm delivery is reduced by several
      factors. The aim of this study was to determine the influence of late pregnancy
      in the uterus-relaxing effect of terbutaline in the rat in vitro. Rat uterine
      tissues from late pregnancy (days 15, 18, 20 and 22) were used. In vitro
      electrical field-stimulation (EFS) was used to evoke contractions. The
      radioligand-binding technique, reverse transcription-polymerase chain reaction
      and radioimmunoassay technique were used to determine the beta-adrenergic
      receptor density and mRNA level and the plasma sex hormone level, respectively.
      The activated G-protein level of the beta-adrenergic receptors was investigated
      by a radiolabelled GTP binding assay.EFS-induced contractions were inhibited by
      terbutaline. This effect decreased towards term with respect to both the EC50 and
      maximal inhibition values. A drop in plasma progesterone level was also detected.
      Binding studies revealed an increase in beta-adrenergic receptor number on the
      last day of pregnancy, which correlated with the change in receptor mRNA level.
      The G-protein-activating effect of terbutaline decreased continuously between
      days 15 and 20. Surprisingly, terbutaline decreased the G-protein activation to
      below the basal level on day 22. However, progesterone pretreatment set back the
      uterine action of terbutaline, increased the density of the beta2-adrenergic
      receptors and their mRNA level and increased the G-protein-activating property of
      terbutaline. These data provide evidence of a pregnancy-induced decrease in
      activated G-protein level after beta2-agonist stimulation. The decrease in plasma
      progesterone level has a crucial role in this process. The effects of beta2
      adrenergic receptor agonists in tocolytic therapy may possibly be potentiated
      with progesterone.

PMID- 15985638
TI  - Mating sequence, dominance and paternity success in captive male tammar
      wallabies.
AB  - The tammar wallaby (Macropus eugenii) is a small, promiscuous, macropodid
      marsupial. Females usually produce a single young each year and there is a clear
      dominance hierarchy between adult males. The dominant male usually mates first
      and then guards the female to prevent access to her by other males. In this
      study, agonistic encounters and mating behaviour were observed to determine male
      dominance hierarchies in six groups of captive tammars consisting of a total of
      23 males and 50 females. Mating behaviour was observed immediately post-partum
      when females were in oestrus and was correlated with plasma testosterone
      concentrations. Male mating sequences were recorded, and the paternity of
      offspring was determined by using seven macropodid marsupial microsatellites.
      Rates of sexual checking and aggression by males housed with females in oestrus
      in the non-breeding season were lower than in the breeding season. These males
      also had lower concentrations of testosterone, but were still able to sire young.
      High testosterone concentrations neither ensured dominance nor appeared to
      control directly the level of sexual activity. Females usually mated with more
      than one male. The dominant male most often secured the initial copulation (60%),
      but the first-mating male did not always secure parentage, with second and third
      matings resulting in as many young as first matings. Using these data, we were
      unable to discount first sire, last sire or equal chance models of paternity in
      this species. Half the young (50%) were sired by the dominant alpha male, but of
      the remaining progeny, the beta male sired more (35%) than gamma and delta males
      (15%). Dominance therefore is only a moderately effective predictor of paternity
      in the tammar. Although the dominant males gained most first matings and
      individually sired half of the offspring, the subdominant males still contributed
      significantly to the population, at least in captivity.

PMID- 15985639
TI  - Influence of IFN-gamma on gene expression in normal human bronchial epithelial
      cells: modulation of IFN-gamma effects by dexamethasone.
AB  - Interferon gamma (IFN-gamma) plays a role in a variety of lung inflammatory
      responses, and corticosteroids are frequently employed as a treatment in these
      conditions. Therefore, the effect of IFN-gamma, of the corticosteroid
      dexamethasone (Dex), or of both on gene expression was studied in normal human
      bronchial epithelial (NHBE) cells. NHBE cells were exposed to medium alone, IFN
      gamma (300 U/ml), Dex (10(-7) M), or both IFN-gamma and Dex for 8 or 24 h. Gene
      expression was examined using oligonucleotide microarrays. A principal components
      analysis demonstrated that the IFN-gamma treatment effect was the primary source
      of differences in the data. With a 5% false discovery rate, of the 66 genes
      upregulated by IFN-gamma by twofold or greater at 8 h and 287 genes upregulated
      at 24 h, coincubation with Dex inhibited the expression of 2 genes at 8 h and 45
      genes at 24 h. Prominent among these were cytokines and secreted proteins. Dex
      cotreatment increased expression of 65 of the 376 genes that were inhibited by
      IFN-gamma by 50% at 24 h. The majority of these genes encode cell cycle or
      nuclear proteins. Dex alone increased the expression of only 22 genes and
      inhibited the expression of 7 genes compared with controls at 24 h. The effect of
      Dex on IFN-gamma-induced changes suggests a specific, targeted effect on IFN
      gamma responses that is substantially greater than the effect of Dex alone. Dex
      had little effect on the immediate early response to IFN-gamma but a significant
      effect on the late responses.

PMID- 15985640
TI  - Wrestling with SUMO in a new arena.
AB  - Sumoylation is a widespread posttranslational modification thought to affect
      primarily nuclear proteins, especially transcription factors for which
      sumoylation usually results in repression of their transactivational function.
      Recent proteomics studies have greatly expanded the cadre of known SUMO
      substrates, and an increasing number of cytoplasmic proteins have been identified
      as SUMO targets. However, very few of these cytosolic proteins have been
      evaluated for the functional consequences of sumoylation. Rajan et al. now
      demonstrate that the activity of an integral cytoplasmic membrane channel-forming
      protein, K2P1, is completely abrogated by sumoylation at a single lysine residue
      on the cytoplasmic tail. This is the first report of a plasma membrane protein as
      a SUMO substrate and explains the long-standing inability to demonstrate
      functionality of K2P1. Apparently, K2P1 is stoichiometrically sumoylated under
      most cellular conditions, so it is constitutively inactive until desumoylated.
      These observations raise several intriguing questions, including: How and where
      does K2P1 become sumoylated? Why, unlike most known substrates, is K2P1 so
      efficiently sumoylated? and, What are the signals and SUMO proteases that trigger
      K2P1 desumoylation? But most importantly, the report by Rajan et al. expands the
      functional roles attributed to sumoylation into the new arena of membrane protein
      functional regulation and suggests that similar mechanisms may regulate the
      function of other pore proteins.

PMID- 15985641
TI  - Quantum-dot-based cell motility assay.
AB  - Because of their favorable physical and photochemical properties, colloidal
      CdSe/ZnS-semiconductor nanocrystals (commonly known as quantum dots) have
      enormous potential for use in biological imaging. In this report, we present an
      assay that uses quantum dots as markers to quantify cell motility. Cells that are
      seeded onto a homogeneous layer of quantum dots engulf and absorb the
      nanocrystals and, as a consequence, leave behind a fluorescence-free trail. By
      subsequently determining the ratio of cell area to fluorescence-free track area,
      we show that it is possible to differentiate between invasive and noninvasive
      cancer cells. Because this assay uses simple fluorescence detection, requires no
      significant data processing, and can be used in live-cell studies, it has the
      potential to be a powerful new tool for discriminating between invasive and
      noninvasive cancer cell lines or for studying cell signaling events involved in
      migration.

PMID- 15985642
TI  - Teaching resources. Glial intercellular waves.
AB  - Glial cells have long been assigned a supporting role in the nervous system, in
      which they help maintain and modulate neuronal metabolism. However, recent
      attention has focused on the ability of astrocytes to propagate long-range
      calcium signals and actively communicate with each other, as well as with neurons
      and vascular cells. Synaptic activity in neurons triggers an increase in the
      intracellular calcium concentration ([Ca2+]i) of neighboring astrocytes,
      stimulating the release of ATP and glutamate. The released ATP stimulates an
      increase in [Ca2+]i in neighboring astrocytes so that a "calcium wave" is
      propagated from cell to cell. Released glutamate is cotransported with Na+ into
      neighboring cells; thus, glutamate uptake leads to an increase in astrocyte
      intracellular sodium concentration ([Na+]i) that is also propagated from cell to
      cell. This increase in [Na+]i stimulates an increase in glucose uptake and
      metabolism that leads to the formation of lactate, which is delivered to nearby-
      and perhaps distant--neurons as an energy substrate. Thus, long-range
      intercellular calcium signaling in astrocytes may enable them to spatially
      coordinate their function in supporting neuronal metabolism.

PMID- 15985643
TI  - Teaching resources. Sensory systems: taste perception.
AB  - This teaching resource provides lecture notes and slides for a class covering the
      human taste system and is part of the course "Cell signaling systems: a course
      for graduate students." The lecture begins with a discussion of five distinct
      qualities of taste and then proceeds to describe receptors and signaling
      mechanisms.

PMID- 15985644
TI  - Socioeconomic risk factors for asthma in Chilean young adults.
AB  - OBJECTIVES: We studied the association between socioeconomic status (SES) and
      asthma symptoms, severity of asthma, atopy, and bronchial hyperresponsiveness
      (BHR) to methacholine. METHODS: We studied 1232 men and women born between 1974
      and 1978 in a semirural area of Chile. We assessed asthma symptoms with a
      standardized questionnaire, atopy with a skin-prick test to 8 allergens, and BHR
      to methacholine with the tidal breathing method. SES was derived from several
      indicators: education, occupation, completion of a welfare form, belongings,
      housing, number of siblings, and overcrowding. RESULTS: Those with fewer
      belongings had more asthma symptoms. Those who had higher education and those who
      owned cars had fewer asthma symptoms and BHR. Overcrowding was negatively related
      to atopy, atopy with asthma symptoms, and BHR. Higher education and noncompletion
      of a welfare form were risk factors for atopy. CONCLUSION: The strength and
      direction of the association between asthma and SES depended on what definition
      of asthma was analyzed. Asthma symptoms were more common among poor people. There
      was some support for the hygiene hypothesis, as overcrowding was associated with
      less wheezing with atopy, less atopy, and less BHR.

PMID- 15985645
TI  - Socioeconomic position in childhood and early adult life and risk of mortality: a
      prospective study of the mothers of the 1958 British birth cohort.
AB  - OBJECTIVES: We sought to establish whether women's childhood socioeconomic
      position influenced their risk of mortality separately from the effects of adult
      socioeconomic position. METHODS: We examined 11855 British women aged 14 to 49
      years, with mortality follow-up over a 45-year period. RESULTS: Trends according
      to childhood social class were observed for all-cause mortality, circulatory
      disease, coronary heart disease, respiratory disease, chronic obstructive
      pulmonary disease, stroke, lung cancer, and stomach cancer, with higher death
      rates among members of unskilled manual groups. Associations attenuated after
      adjustment for adult social class, smoking, and body mass index. No trend was
      seen for breast cancer or accidents and violence. Adverse social conditions in
      both childhood and adulthood were associated with higher death rates from
      coronary heart disease and respiratory disease. Stomach cancer was influenced
      primarily by childhood conditions and lung cancer by factors in adult life.
      CONCLUSIONS: Socioeconomic position in childhood was associated with adult
      mortality in a large sample of British women.

PMID- 15985646
TI  - Emergency contraception in emergency departments in Oregon, 2003.
AB  - OBJECTIVES: We sought to learn about access to emergency contraception (EC) in
      Oregon emergency departments, both for women who are rape patients and for women
      who have had consensual unprotected sexual intercourse ("nonrape patients").
      METHODS: We interviewed emergency department staff in 54 of Oregon's 57 licensed
      emergency departments in February-March 2003 (response rate = 94.7%). RESULTS:
      Only 61.1% of Oregon emergency departments routinely offered EC to rape patients.
      Catholic hospitals were as likely as non-Catholic hospitals to routinely offer EC
      to rape patients. The hospitals most likely to routinely offer EC to rape
      patients had a written protocol for the care of rape patients that included
      offering EC (P = .02) and access to staff with specialized sexual assault
      training (P=.002). For nonrape patients, 46.3% of emergency departments
      discouraged the prescribing of EC. Catholic hospitals were significantly less
      likely than non-Catholic hospitals to provide access to EC for nonrape patients
      (P=.05). CONCLUSIONS: Oregon emergency departments do not routinely offer EC to
      women who have been raped or to women who have had consensual unprotected sexual
      intercourse.

PMID- 15985647
TI  - Perception of dental illness among persons receiving public assistance in
      Montreal.
AB  - OBJECTIVES: We examined rationales for behaviors related to dental care among
      persons receiving public assistance in Montreal, Quebec. METHODS: Fifty-seven
      persons receiving public assistance participated in 8 focus groups conducted in
      2002. Sessions were recorded on audiotape and transcribed; analyses included
      debriefing sessions and coding and interpreting transcribed data. RESULTS: In the
      absence of dental pain and any visible cavity, persons receiving public
      assistance believed they were free of dental illness. However, they knew that
      dental pain signals a pathological process that progressively leads to tooth
      decay and, therefore, should be treated by a dentist. However, when in pain,
      despite recognizing that they needed professional treatment, they preferred to
      wait and suffer because of a fear of painful dental treatments and a reluctance
      to undertake certain procedures. CONCLUSIONS: Persons receiving public assistance
      have perceptions about dental health and illness that prevent them from receiving
      early treatment for tooth decay, which may lead to disagreements with dentists
      when planning dental treatments.

PMID- 15985648
TI  - The economic burden of home care for children with HIV and other chronic
      illnesses.
AB  - OBJECTIVES: We compared types, amounts, and costs of home care for children with
      HIV and chronic illnesses, controlling for the basic care needs of healthy
      children to determine the economic burden of caring for and home care of
      chronically ill children. METHODS: Caregivers of 97 HIV-positive children, 101
      children with a chronic illness, and 102 healthy children were surveyed regarding
      amounts of paid and unpaid care provided. Caregiving value was determined
      according to national hourly earnings and a market replacement method. RESULTS:
      Chronically ill children required significantly more care time than HIV-positive
      children (7.8 vs 3.9 hours per day). Paid care accounted for 8% to 16% of care
      time. Annual costs were $9300 per HIV-positive child and $25,900 per chronically
      ill child. Estimated national annual costs are $86.5 million for HIV-positive
      children and $155 to $279 billion for chronically ill children. CONCLUSIONS:
      Informal caregiving represents a substantial economic value to society. The total
      care burden among chronically ill children is higher than that among children
      with HIV.

PMID- 15985649
TI  - HIV incidence among injection drug users in New York City, 1990 to 2002: use of
      serologic test algorithm to assess expansion of HIV prevention services.
AB  - OBJECTIVES: We sought to estimate HIV incidence among injection drug users (IDUs)
      in New York City from 1990 to 2002 to assess the impact of an expansion of
      syringe exchange services. Syringe exchange increased greatly during this period,
      from 250,000 to 3,000,000 syringes exchanged annually. METHODS: Serum samples
      were obtained from serial cross-sectional surveys of 3,651 IDUs. HIV-positive
      samples were tested with the Serologic Test Algorithm for Recent HIV
      Seroconversion (STARHS) assay to identify recent HIV infections and to estimate
      HIV incidence. Consistency with other incidence studies was used to assess
      strengths and limitations of STARHS. RESULTS: HIV incidence declined from
      3.55/100 person-years at risk (PYAR) from 1990-1992, to 2.63/100 PYAR from 1993
      1995, to 1.05/100 PYAR from 1996-1998, and to 0.77/100 PYAR from 1999-2002
      (P<.001). There was a very strong negative linear relationship (r= -.99, P<.005)
      between the annual numbers of syringes exchanged and estimated HIV incidence.
      These results were highly consistent with a large number of shorter incidence
      studies among IDUs conducted during the time period. CONCLUSIONS: STARHS testing
      of samples from large serial cross-sectional surveys can provide important data
      for the assessment of community-level HIV prevention.

PMID- 15985650
TI  - cPLA2-interacting protein, PLIP, causes apoptosis and decreases G1 phase in
      mesangial cells.
AB  - The balance between proliferation and apoptosis of mesangial cells is a critical
      component of proliferative glomerulonephritis. The regulation of cell
      proliferation and apoptosis is linked at the level of the cell cycle (Shankland
      SJ. Kidney Int 52: 294-308, 199). cPLA2-interacting protein (PLIP), the Tip60
      splice variant, interacts with cPLA2 and enhances the susceptibility of renal
      mesangial cells to serum deprivation-induced apoptosis (Sheridan AM, Force T,
      Yoon HJ, O'Leary E, Choukroun G, Taheri MR, and Bonventre JV. Mol Cell Biol 21:
      4470-4481, 2001). We report that adenoviral-driven PLIP expression results in
      enhanced apoptosis of non-serum-deprived mesangial cells associated with a marked
      decrease in G0/G1 phase cells. The effect of PLIP on the cell cycle may be
      independent of its interaction with cPLA2 because a mutation of PLIP that does
      not interact with cPLA2 also causes a decrease in G0/G1 cells. Endogenous PLIP
      and Tip60 protein levels are increased in cells exposed to injurious stimuli
      including X-irradiation and H2O2, but the intracellular localization of the
      splice variants may differ. Whereas PLIP localizes in the nucleus of all
      mesangial cells, Tip60 localizes in the cytosol of untreated mesangial cells and
      of cells exposed to low concentrations (50-200 microM) of H2O2. Tip60 is targeted
      to the nucleus of cells exposed to high concentrations (1-2 mM) of H2O2. We
      conclude that PLIP may cause cells to exit from the cell cycle after the S phase
      and may function as part of a G2/M checkpoint mechanism. Tip60 splice variants
      may function in both cytosolic and nuclear signaling pathways in mesangial cells.

PMID- 15985651
TI  - Prostaglandin E2 EP2 and EP4 receptor activation mediates cAMP-dependent
      hyperpolarization and exocytosis of renin in juxtaglomerular cells.
AB  - PGE(2) and PGI(2) stimulate renin secretion and cAMP accumulation in
      juxtaglomerular granular (JG) cells. We addressed, at the single-cell level, the
      receptor subtypes and intracellular transduction mechanisms involved. Patch clamp
      was used to determine cell capacitance (C(m)), current, and membrane voltage in
      response to PGE(2), EP2 and EP4 receptor agonists, and an IP receptor agonist.
      PGE(2) (0.1 micromol/l) increased C(m) significantly, and the increase was
      abolished by intracellular application of the protein kinase A antagonist Rp-8
      CPT-cAMPS. EP2-selective ligands butaprost (1 micromol/l), AE1-259-01 (1 nmol/l),
      EP4-selective agonist AE1-329 (1 nmol/l), and IP agonist iloprost (1 micromol/l)
      significantly increased C(m) mediated by PKA. The EP4 antagonist AE3-208 (10
      nmol/l) blocked the effect of EP4 agonist but did not alter the response to
      PGE(2). Application of both EP4 antagonist and EP2-antagonist AH-6809 abolished
      the effects of PGE(2) on C(m) and current. EP2 and EP4 ligands stimulated cAMP
      formation in JG cells. PGE(2) rapidly stimulated renin secretion from superfused
      JG cells and diminished the membrane-adjacent granule pool as determined by
      confocal microscopy. The membrane potential hyperpolarized significantly after
      PGE(2), butaprost, AE1-329 and AE1-259 and outward current was augmented in a PKA
      dependent fashion. PGE(2)-stimulated outward current, but not C(m) change, was
      abolished by the BK(Ca) channel inhibitor iberiotoxin (300 nmol/l). EP2 and EP4
      mRNA was detected in sampled JG cells, and the preglomerular and glomerular
      vasculature was immunopositive for EP4. Thus IP, EP2, and EP4 receptors are
      associated with JG cells, and their activation leads to rapid PKA-mediated
      exocytotic fusion and release of renin granules.

PMID- 15985652
TI  - Posttranscriptional control of aquaporin-2 abundance by vasopressin in renal
      collecting duct principal cells.
AB  - Prevailing expression levels of aquaporin-2 (AQP2) mRNA play a major role in
      regulating AQP2 protein abundance. Here, we investigated whether AQP2 protein
      abundance is regulated at a posttranscriptional level as well. The expression
      levels of both AQP2 mRNA and protein increase in response to arginine vasopressin
      (AVP) in a concentration- and time-dependent manner in cultured immortalized
      mouse collecting duct principal cells (mpkCCD(cl4) cells). AVP washout from the
      medium of AVP-pretreated cells revealed that AQP2 mRNA expression progressively
      decreased over time, whereas AQP2 protein abundance first increased immediately
      after AVP washout and then gradually decreased over time. Inversely, increasing
      AVP concentration led to a time-dependent increase of AQP2 mRNA, whereas AQP2
      protein abundance first decreased immediately after AVP supplementation and then
      gradually increased over time. These transient effects arose from altered V2
      receptor activity because they could be abolished by SR-121463B, a specific V2
      receptor antagonist. Although cycloheximide administration had no effect on
      transient alterations of AQP2 protein content, these effects were attenuated by
      administration of chloroquine, a lysosomal inhibitor, or lactacystin, a
      proteasomal inhibitor. Short-term inhibition of PKA activity significantly
      increased AQP2 protein abundance and blunted the transient alterations of AQP2
      protein content induced by AVP washout and supplementation. In addition,
      phosphorylated AQP2 abundance increased immediately after AVP supplementation.
      These results indicate that in response to AVP AQP2 protein abundance in
      collecting duct principal cells is principally influenced by AQP2 mRNA content
      but is additionally regulated by PKA-dependent negative feedback acting on AQP2
      protein degradation.

PMID- 15985654
TI  - Proteomic analysis of human neutrophil granules.
AB  - Stimulated exocytosis of intracellular granules plays a critical role in
      conversion of inactive, circulating neutrophils to fully activated cells capable
      of chemotaxis, phagocytosis, and bacterial killing. The functional changes
      induced by exocytosis of each of the granule subsets, gelatinase (tertiary)
      granules, specific (secondary) granules, and azurophil (primary) granules, are
      poorly defined. To improve the understanding of the role of exocytosis of these
      granule subsets, a proteomic analysis of the azurophil, specific, and gelatinase
      granules from human neutrophils was performed. Two different methods for granule
      protein identification were applied. First, two-dimensional (2D) gel
      electrophoresis followed by MALDI-TOF MS analysis of peptides obtained by in-gel
      trypsin digestion of proteins was performed. Second, peptides from tryptic
      digests of granule membrane proteins were separated by two-dimensional
      microcapillary chromatography using strong cation exchange and reverse phase
      microcapillary high pressure liquid chromatography and analyzed with electrospray
      ionization tandem mass spectrometry (2D HLPC ESI-MS/MS). Our analysis identified
      286 proteins on the three granule subsets, 87 of which were identified by MALDI
      MS and 247 were identified by 2D HPLC ESI-MS/MS. The increased sensitivity of 2D
      HPLC ESI-MS/MS, however, resulted in identification of over 500 proteins from
      subcellular organelles contaminating isolated granules. Defining the proteome of
      neutrophil granule subsets provides a basis for understanding the role of
      exocytosis in neutrophil biology. Additionally, the described methods may be
      applied to mobilizable compartments of other secretory cells.

PMID- 15985655
TI  - Attorney abuses of Daubert hearings: junk science, junk law, or just plain
      obstruction?

PMID- 15985656
TI  - Death row syndrome and demoralization: psychiatric means to social policy ends.

PMID- 15985657
TI  - Just whose culture is it, anyway?

PMID- 15985658
TI  - Quality and quality improvement in forensic mental health evaluations.
AB  - Despite the growing attention to quality and quality improvement in health care
      in the United States, forensic psychiatry has yet to incorporate relevant
      developments and information and make quality an important item on the agenda.
      This article reviews the empirical research regarding the perceived quality of
      forensic evaluations, which has primarily examined criminal rather than civil
      forensic evaluations. Beyond the available research, many important policy and
      empirical questions must be addressed, including the definition of a quality
      forensic evaluation, the process used to access quality, the indicators and
      measures used, the methods that provide incentives for performing quality
      evaluations, the role of forensic psychiatry training programs, and the role of
      the American Academy of Psychiatry and the Law (AAPL) or other professional
      organizations in the quality improvement enterprise.

PMID- 15985659
TI  - On sound and unsound mind: the role of suicide in tort and insurance litigation.
AB  - Suicide continues to be a recognized as a crime by common law in a few states. In
      those jurisdictions, the beneficiary of a claim must prove that the individual
      who attempted or committed suicide was of unsound mind, to avoid having the
      patient's act declared illegal, which would bar recovery of the claim. In
      malpractice and insurance cases, expert testimony is required regarding the
      mental state of the individual who attempted or committed suicide. Psychiatric
      testimony varies widely, depending on the legal definition of "unsound mind" and
      the highly subjective interpretation of legal definitions. Some experts equate
      suicide with an unsound mind, whereas others apply M'Naghten criteria. Some
      psychiatrists who disagree with criminalizing suicide refuse to participate in
      these proceedings. In suicide malpractice cases, the appropriate function of the
      expert witness is to provide testimony about the standard of care. When experts
      attempt to testify about "sound or unsound" mind, they must be mindful of the
      imperfect fit between psychiatry and the law.

PMID- 15985660
TI  - Commentary: responsibility and insurance coverage of the mentally ill.
AB  - Should criminal law principles be applied to life insurance claims made by the
      beneficiaries of an insured person who commits suicide? Any discussion of the
      criminal law and the M'Naghten test of criminal responsibility, as sometimes used
      by the courts and recommended by the authors, obfuscates the resolution of
      contemporary issues.

PMID- 15985661
TI  - Gender differences in criminality: bipolar disorder with co-occurring substance
      abuse.
AB  - Outpatient interviews to collect criminal history data were conducted with 55
      women and 77 men who had the dual diagnosis of rapid-cycling bipolar disorder
      with co-morbid substance abuse disorders (DD-RCBD), to ascertain gender-related
      similarities and differences. Fifty-three percent of women and 79 percent of men
      reported that they had been charged with a crime, and nearly half of those
      charged had been incarcerated. Men with DD-RCBD were more likely to have
      committed a felony and had a trend of committing more misdemeanors. Although
      women with DD-RCBD were less likely to have a criminal history than their male
      counterparts, they were far more likely to have a criminal history than were
      women in the general population. Implications from this pilot study include the
      need for earlier identification of bipolar disorder and for the increased
      availability of psychiatric and substance abuse services within correctional
      facilities.

PMID- 15985662
TI  - Commentary: substance abuse and criminality in the mentally disordered defendant.
AB  - This commentary discusses the main findings of the research study by Friedman et
      al. entitled, "Gender Differences in Criminality: Bipolar Disorder with Co
      occurring Substance Abuse." Moreover, it shows that the role of substance use
      should be determined in studies that assess outcomes among co-occurring
      disorders, such as bipolar disorder and criminal behavior. High rates of
      substance-related problems were recorded in the study by Friedman et al. Fifty
      six percent of the patients with dual-diagnosis, rapid-cycling bipolar disorder
      had been charged with drug- or alcohol-related offenses. Significantly more men
      (69%) had incurred substance-related charges than had women (38%). Women who
      abused cocaine were more likely to be charged with a crime than were those who
      had not. Sixty-five percent of the women in the study who abused cocaine had been
      previously charged with a crime, compared with 38 percent of the women who did
      not; but this finding did not hold true for the men. The number of crimes
      committed by the men who abused cocaine and by those who did not was about the
      same. This article also provides an overview of the role of substance use in
      criminal behavior and how substances of abuse can affect bipolar disorder and
      criminal outcomes.

PMID- 15985663
TI  - Purpose and utility of child custody evaluations: the attorney's perspective.
AB  - This study attempts to fill a gap in the literature by assessing the perspectives
      of attorneys regarding child custody evaluations completed by mental health
      professionals. Fifty-nine attorneys completed an anonymous survey designed to
      ascertain their opinions about: (1) what factors prompt a custody evaluation, (2)
      expectations regarding evaluation procedures, (3) the utility of the resultant
      report, and (4) the impact of evaluations on litigation. Findings indicate that
      attorneys are most likely to seek child custody evaluations in the context of
      allegations regarding physical abuse, sexual abuse, or parental fitness. In
      addition, attorneys reported that they expect a very comprehensive evaluation
      procedure and find utility in an inclusive report. Finally, survey findings
      suggest that custody evaluations play a significant role in decisions to
      negotiate a settlement rather than proceed to trial. Limited available research
      and current practice related to these findings are reviewed.

PMID- 15985664
TI  - Juror knowledge and attitudes regarding mental illness verdicts.
AB  - We begin with a brief overview of the Not Guilty by Reason of Insanity (NGRI) and
      Guilty but Mentally Ill (GBMI) verdicts in the United States and then report on a
      study of qualified jurors (n=96) in which we examined jurors' understanding and
      attitudes about mental illness verdicts and the disposition of mentally ill
      defendants. Results indicate that although the jury pool was highly educated,
      only 4.2 percent of jurors could correctly identify both the definitions and
      dispositions of defendants found NGRI and GBMI. Jurors with lower educational
      levels were less likely to identify the dispositional outcome of a GBMI verdict
      (p<.05). Eighty-four percent of respondents believed that juries should be
      informed of dispositional outcome before deciding a verdict. Also, 68.4 percent
      of jurors erroneously believed that a defendant found GBMI could not receive the
      death penalty. Among jurors who correctly identified the definition of GBMI,
      those with lower educational levels were more punitive in their attitudes toward
      disposition of the GBMI defendants, believing they should eventually be sent to
      prison (p<.05).

PMID- 15985665
TI  - A cognitive, behaviorally based program for patients with persistent mental
      illness and a history of aggression, crime, or both: structure and correlates of
      completers of the program.
AB  - Standard psychiatric treatment programs have limited success in reducing
      recidivistic violent and criminal behavior in patients with persistent mental
      illness. A specialized, cognitive behavioral treatment program was developed for
      such a population. The purpose of this study was to identify factors that
      contribute to the patients' completing the program and to improve the selection
      criteria for program admission, so that those who participate are more likely to
      complete the program and be discharged. One hundred eighty-one patients with
      persistent mental illness with histories of aggression, crime, or both
      participated in a cognitive skills inpatient treatment program adapted for use
      with psychiatric patients. Ninety patients were able to complete the program and
      were discharged into the community. In comparison with the 91 who did not
      complete the program, those who did were less cognitively impaired and less
      impulsive. We present a new, intensive treatment program and define the
      predictors of successful completion of the program.

PMID- 15985666
TI  - A comparison of incest offenders based on victim age.
AB  - The purpose of the present study was to compare incest offenders (IOs) whose
      victims include infants or toddlers to IOs with adolescent victims on several
      variables commonly examined in the sexual offender literature. Participants were
      48 men whose youngest victim was less than 6 years of age (younger-victim incest
      offenders; YVs); and 71 men whose youngest victim was 12 to 16 years of age
      (older-victim incest offenders (OVs). In general, YVs showed more emotional
      disturbance and pathology than OVs. Compared with OVs, YVs had a greater history
      of substance abuse and more current problems with alcohol. In addition, YVs
      reported significantly poorer sexual functioning and were significantly more
      psychiatrically disturbed. YVs were also more likely to have a male victim, to
      have victimized a nephew/niece or grandson/granddaughter, and to have denied
      their offense(s). It was evident that both the YVs and OVs demonstrated
      clinically significant difficulty with normal sexual functioning and exhibited
      deviant sexual arousal.

PMID- 15985668
TI  - "May you stay forever young": Robert Sadoff and the history of mental disability
      law.

PMID- 15985669
TI  - The history of legal medicine.

PMID- 15985670
TI  - "What's in a name?": A brief foray into the history of insanity in England and
      the United States.

PMID- 15985671
TI  - The history of forensic psychiatry.

PMID- 15985672
TI  - The present and future of forensic psychiatry.

PMID- 15985681
TI  - Wiggins v. Smith 539 U.S. 510 (2003).

PMID- 15985683
TI  - Secondary structural characterization of oligonucleotide strands using
      electrospray ionization mass spectrometry.
AB  - Differences in charge state distributions of hairpin versus linear strands of
      oligonucleotides are analyzed using electrospray ionization mass spectrometry
      (ESI-MS) in the negative ion detection mode. It is observed that the linear
      structures show lower charge state distribution than the hairpin strands of the
      same composition. The concentration of ammonium acetate and the cone voltage are
      major factors that cause the shift of the negative ions in the charge states. The
      ESI data presented here are supported by UV spectra of strands acquired at 260 nm
      wavelength in aqueous ammonium acetate solution. We will show that the strands
      that demonstrate a higher charge state distribution in the gas phase also have a
      higher melting temperature in solution.

PMID- 15985684
TI  - Identification of mixed di-cation forms of G-quadruplex in solution.
AB  - Multinuclear NMR study has demonstrated that G-quadruplex adopted by d(G3T4G4)
      exhibits two cation binding sites between three of its G-quartets. Titration of
      tighter binding K+ ions into the solution of d(G3T4G4)2 folded in the presence of
      15NH4+ ions uncovered a mixed mono-K+-mono-15NH4+ form that represents
      intermediate in the conversion of di-15NH4+ into di-K+ form. Analogously, 15NH4+
      ions were found to replace Na+ ions inside d(G3T4G4)2 quadruplex. The preference
      of 15NH4+ over Na+ ions for the two binding sites is considerably smaller than
      the preference of K+ over 15NH4+ ions. The two cation binding sites within the G
      quadruplex core differ to such a degree that 15NH4+ ions bound to the site, which
      is closer to the edge-type loop, are always replaced first during titration by K+
      ions. The second binding site is not taken up by K+ ion until K+ ion already
      resides at the first binding site. Quantitative analysis of concentrations of the
      three di-cation forms, which are in slow exchange on the NMR time scale, at 12 K+
      ion concentrations afforded equilibrium binding constants. K+ ion binding to
      sites U and L within d(G3T4G4)2 is more favorable with respect to 15NH4+ ions by
      Gibbs free energies of approximately -24 and -18 kJ mol(-1) which includes
      differences in cation dehydration energies, respectively.

PMID- 15985685
TI  - Neonatal glucocorticosteroid treatment causes systolic dysfunction and
      compensatory dilation in early life: studies in 4-week-old prepubertal rats.
AB  - Glucocorticosteroid treatment is widely used to prevent chronic lung disease in
      premature infants. Recent studies in adult rats, treated with dexamethasone in
      the neonatal period, report negative long-term effects on the heart and severely
      reduced life expectancy. We treated neonatal rats with dexamethasone and studied
      cardiac function after 4 wk (prepubertal age) to investigate whether the late
      effects as previously described are preceded by detectable alterations in cardiac
      function at a younger age. Male rat pups (n = 12) were injected intraperitoneally
      with dexamethasone on d 1, 2, and 3 (0.5, 0.3, and 0.1 mug/g) of life. Control
      pups (n = 10) received saline. At 4 wk the animals were anesthetized, and a
      pressure-conductance catheter was introduced into the left ventricle to measure
      pressure-volume loops. Cardiac function was measured and pressure-volume
      relations were determined to quantify intrinsic systolic and diastolic function.
      Subsequently, hearts were excised for histologic examination. Compared with
      saline-treated animals, dexamethasone-treated rats had a reduced ventricular
      weight (270 +/- 40 versus 371 +/- 23 mg, p < 0.001) and reduced systolic function
      (end-systolic elastance: 1.24 +/- 0.43 versus 2.50 +/- 1.39 mm Hg/muL, p =
      0.028). Cardiac output was maintained and end-diastolic volume was increased (84
      +/- 23 versus 59 +/- 19 microL, p = 0.012) indicating a state of compensatory
      dilatation. Heart rate, diastolic function, and systemic vascular resistance were
      unchanged. Neonatal dexamethasone treatment causes cardiac alterations that can
      be detected in the prepubertal period and that may precede severe cardiac
      dysfunction later in life. If our findings are confirmed in humans, this may have
      consequences for a large patient population and cardiac screening at young age
      may be indicated to enable secondary prevention.

PMID- 15985686
TI  - The COMT val158met polymorphism is associated with early pubertal development,
      height and cortical bone mass in girls.
AB  - Estrogens are involved in accretion of bone mass during puberty. Catechol-O
      Methyltransferase (COMT) is involved in the degradation of estrogens. In this
      cross-sectional study we investigated associations between the COMT val158met
      polymorphism, which results in a 60-75% difference in enzyme activity between the
      val (high activity = H) and the met (low activity = L) variant, and skeletal
      phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4
      cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of
      bone mineral content (BMC), and larger areas of total body, femur and spine in
      COMT(LL). Cortical BMC, measured by peripheral quantitative computerized
      tomography in the tibia, was 9.8% higher in COMT(LL) compared with COMT(HH). This
      was due to a larger cortical cross sectional area while the cortical volumetric
      bone mineral density was not associated with COMT genotype. COMT(LL) girls had
      higher serum levels of free estradiol and insulin like growth factor. Regression
      models indicated that COMT genotype exerted effects on skeletal growth mainly via
      a regulation of free estradiol, resulting in an affected pubertal development
      (Tanner staging). We propose that the COMT(LL) genotype results in higher free
      estradiol levels and earlier pubertal development, leading to an increased
      skeletal growth in pre/early pubertal girls. Possible consequences for the adult
      skeleton however can be determined only after cessation of growth.

PMID- 15985687
TI  - Variation in the interleukin-6 gene is associated with impaired cognitive
      development in children born prematurely: a preliminary study.
AB  - The pro-inflammatory cytokine IL-6 may be neurocytopathogenic, and elevated
      levels are associated with impaired neurological outcome among children born
      prematurely. However, the precise mechanisms underlying this association remain
      unclear. The rare C (rather than G) variant at position -572 in the IL-6 gene is
      associated with an increased IL-6 synthetic response. If IL-6 mediates cerebral
      injury, we would anticipate the -572 C allele to be associated with impaired
      childhood development. We have examined this hypothesis, studying 113 Caucasian
      children born at < or =32 wk gestation. Cognitive and motor functions were
      assessed using the Griffiths Developmental Scales at 2 y and British Ability
      Scales (2nd Ed.) and the ABC Movement Score at 51/2 y. Performance (median,
      interquartile range) in all three scales was worse in the 10 carriers of the C
      allele than for those with GG genotype: Griffiths Developmental Quotient: C
      allele, 92.4 (89.9-96.6) versus CG 100.9 (96.7-104.8), p = 0.002; General
      Cognitive Ability: C allele, 88.0 (80.3-102.8) versus GG 103.0 (92.0-112.0), p =
      0.037; Movement ABC score: C allele 8.3 (6.6-20.3) versus GG 4.0 (1.0-9.5), p =
      0.081. The presence of the rare (> or =1) IL-6 -572 C-allele (CC+GC genotypes) is
      associated with impaired cognitive development among children born before 32 wk
      gestation. These data support a role for IL-6 in the genesis of neurologic
      impairment in such children.

PMID- 15985688
TI  - Rapid diagnosis of bacterial sepsis with PCR amplification and microarray
      hybridization in 16S rRNA gene.
AB  - In this study, blood culture and PCR-microarray analysis were used to examine 172
      cases of suspected septicemia. Primers and oligonucleotide probes, based on the
      sequences of bacterial 16SrRNA gene, were arrayed by imprinting on microarray
      slides. Blood specimens collected from 172 cases of suspected septicemia were
      cultured and then tested separately by PCR for the bacterial 16S rRNA. Of the 172
      clinical cases, 17 cases tested positive by PCR. The number of positives
      identified by PCR (9.88%) was significantly higher than the number of positives
      identified by the blood culture (4.65%). When blood culture was used as control,
      the sensitivity of PCR was 100%, the specificity was 97.85%, and the index of
      accurate diagnosis was 0.979. When the 17 PCR positive specimens were further
      analyzed by hybridization against the microarrays, five were found to be probe
      positive for E. coli, four were positive for S. epidermidis, four were positive
      for CoNS, and two were positive for Bacillus and Propionibacterium, respectively.
      In the eight specimens showing positive results by both PCR and blood culture,
      the species determined by microarray analysis corresponded with the result
      obtained from blood culture. Detection of the bacterial 16SrRNA genes in clinical
      specimens by PCR and microarray analysis can be used to accurately diagnose
      neonatal sepsis. This method has a higher sensitivity and specificity than blood
      culture and can provide a rapid way for the etiological diagnosis of neonatal
      septicemia.

PMID- 15985690
TI  - Aristides Leao's discovery of cortical spreading depression.

PMID- 15985691
TI  - Dr. Bernice Grafstein's paper on the mechanism of spreading depression.

PMID- 15985692
TI  - Statistical issues in the analysis of neuronal data.
AB  - Analysis of data from neurophysiological investigations can be challenging.
      Particularly when experiments involve dynamics of neuronal response, scientific
      inference can become subtle and some statistical methods may make much more
      efficient use of the data than others. This article reviews well-established
      statistical principles, which provide useful guidance, and argues that good
      statistical practice can substantially enhance results. Recent work on estimation
      of firing rate, population coding, and time-varying correlation provides
      improvements in experimental sensitivity equivalent to large increases in the
      number of neurons examined. Modern nonparametric methods are applicable to data
      from repeated trials. Many within-trial analyses based on a Poisson assumption
      can be extended to non-Poisson data. New methods have made it possible to track
      changes in receptive fields, and to study trial-to-trial variation, with modest
      amounts of data.

PMID- 15985693
TI  - Thalamocortical specificity and the synthesis of sensory cortical receptive
      fields.
AB  - A persistent and fundamental question in sensory cortical physiology concerns the
      manner in which receptive fields of layer-4 neurons are synthesized from their
      thalamic inputs. According to a hierarchical model proposed more than 40 years
      ago, simple receptive fields in layer 4 of primary visual cortex originate from
      the convergence of highly specific thalamocortical inputs (e.g., geniculate
      inputs with on-center receptive fields overlap the on subregions of layer 4
      simple cells). Here, we summarize studies in the visual cortex that provide
      support for this high specificity of thalamic input to visual cortical simple
      cells. In addition, we review studies of GABAergic interneurons in the
      somatosensory "barrel" cortex with receptive fields that are generated by a very
      different mechanism: the nonspecific convergence of thalamic inputs with
      different response properties. We hypothesize that these 2 modes of
      thalamocortical connectivity onto subpopulations of excitatory and inhibitory
      neurons constitute a general feature of sensory neocortex and account for much of
      the diversity seen in layer-4 receptive fields.

PMID- 15985694
TI  - Sex differences in the brain: plasticity and constraints. Focus on "Androgen
      induced vocal transformation in adult female african clawed frogs".

PMID- 15985695
TI  - Functional characterization of des-IGF-1 action at excitatory synapses in the CA1
      region of rat hippocampus.
AB  - Insulin-like growth factor-1 (IGF-1) and growth hormone play a major role in the
      growth and development of tissues throughout the mammalian body. Plasma IGF-1
      concentrations peak during puberty and decline with age. We have determined that
      chronic treatments to restore plasma IGF-1 concentrations to adult levels
      attenuate spatial learning deficits in aged rats, but little is known of the
      acute actions of IGF-1 in the brain. To this end, we utilized hippocampal slices
      from young Sprague-Dawley rats to characterize the acute effects of des-IGF-1 on
      excitatory synaptic transmission in the CA1 region. We observed a 40% increase in
      field excitatory postsynaptic potential (fEPSP) slope with application of des-IGF
      1 (40 ng/ml) and used whole cell patch-clamp recordings to determine that this
      enhancement was due to a postsynaptic mechanism involving alpha-amino-3-hydroxyl
      5-methyl-4-isoxazolepropionate (AMPA) but not N-methyl-D-aspartate receptors.
      Furthermore, the enhancement was completely blocked by the broad-spectrum
      tyrosine kinase inhibitor, genistein (220 microM), and significantly reduced by
      the PI3K blockers wortmannin (1 microM) and 2-(4-morpholinyl)-8-phenyl-4H-1
      benzopyran-4-one (10 microM), suggesting that the effect was predominantly
      dependent on PI3K activation. This characterization of the acute actions of des
      IGF-1 at hippocampal excitatory synapses may provide insight into the mechanism
      by which long-term increases in plasma IGF-1 impart cognitive benefits in aged
      rats. Increases in AMPA receptor-mediated synaptic transmission may contribute
      directly to cognitive improvement or initiate long-term changes in synthesis of
      proteins such as brain-derived neurotrophic factor that are important to learning
      and memory.

PMID- 15985696
TI  - Reduced functional recovery by delaying motor training after spinal cord injury.
AB  - The purpose of this study was to examine if a delay in rehabilitative motor
      training after spinal cord injury affects functional motor recovery. We studied a
      skilled motor task in which rats traversed a raised horizontal ladder and we
      quantified errors in accurate stepping, i.e., foot slips between rungs. After
      lesions to the dorsal quadrant of the thoracic (T8) spinal cord that aimed to
      unilaterally sever the corticospinal and rubrospinal tracts, rats were re-trained
      to walk across the ladder, either immediately after injury or after a 3-mo delay.
      Before training, the error rate in accurate stepping of the affected hindlimb was
      similar in the immediately (69.4 +/- 5.3%) and delay (62.7 +/- 4.1%; means +/-
      SE)-trained animals (not significantly different), suggesting that accurate
      stepping did not improve spontaneously if rats were not exposed to the ladder.
      After a 3-wk course of training (30 runs across the ladder per day, 5 day/wk),
      improvements in accurate stepping performance were greater if training was
      implemented immediately after injury. On average, immediately trained animals
      improved stepping performance by 61.5 +/- 28.2%, whereas the delay trained group
      improved by only 34.9 +/- 28.8% (significantly different). The degree of damage
      to the corticospinal and rubrospinal tracts was very similar in the two groups of
      animals, indicating that differences in lesion size did not contribute to the
      differences in performance improvement. Animals with large lesions to the
      corticospinal and rubrospinal tracts (>70%) displayed poor recovery from training
      (especially for delay-trained animals), suggesting that these two pathways were
      important in mediating improvements in accurate stepping. In addition, recovery
      of stepping-like reflexes appeared not to contribute to the recovery of accurate
      stepping given that the time course of reflex recovery was not related to the
      time course of recovery of accurate stepping. We conclude that training of a
      skilled motor task that relies on descending control is more beneficial when
      initiated immediately after a partial spinal cord injury.

PMID- 15985697
TI  - Probing the endogenous Ca2+ buffers at the presynaptic terminals of the crayfish
      neuromuscular junction.
AB  - Ca2+ indicators of varying affinity and mobility were pressure injected into the
      presynaptic axon of the inhibitor of the crayfish neuromuscular junction (NMJ).
      Fluorescence transients recorded at a 2-kHz resolution were used to probe
      physiological parameters governing the decay of fluorescence transients within
      100 ms after an action potential (early decay). Blocking Ca2+ extrusion or Ca2+
      sequestration processes did not significantly alter early decay, arguing against
      a role for either mechanism. Fluorescence transients recorded with low mobility
      or fixed indicators exhibited early decay similar to that recorded with
      indicators of comparable affinity but high mobility, suggesting that early decay
      was not due to the rate of Ca2+-indicator diffusion. The extent of early decay
      correlated closely with the affinity, but not mobility, of the Ca2+ sensitive
      dyes tested. These results implicate intrinsic buffers with slow Ca2+ binding
      kinetics as the most likely determinants of early decay. However, computer
      simulations showed that intrinsic buffers with a slow binding rate are unlikely
      to be the only ones present in the system because the slow kinetics would be
      unable to buffer incoming Ca2+ during an action potential and would result in
      momentary indicator saturation. In fact, experimental data show that the peak
      amplitude of an action potential activated Ca+ transient is about 20% of the
      maximal fluorescence intensity activated by prolonged Ca2+ influx. We conclude
      that endogenous buffering at the crayfish NMJ includes both fast and slow
      components, the former being fast enough to compete with fast Ca2+ indicators,
      and the latter dictating the early decay.

PMID- 15985698
TI  - Calcium-stimulated adenylyl cyclases required for long-term potentiation in the
      anterior cingulate cortex.
AB  - Activity-dependent long-term potentiation (LTP) in the CNS is thought to be
      important in learning, memory, development, and persistent pain. Here, we report
      that NMDA receptor-dependent LTP is the major form of long-term plasticity in the
      anterior cingulate cortex (ACC). In addition to N-methyl-D-aspartate (NMDA)
      receptors, L-type voltage-gated calcium channels are also required for inducing
      LTP. Activation of calcium-stimulated adenylyl cyclase subtype 1 (AC1) is
      essential for the induction of LTP in ACC neurons, while AC8 subunit partially
      contributes to forskolin-induced potentiation. Our results suggest that calcium
      stimulated cAMP-dependent signaling pathways play a critical role in cingulate
      LTP.

PMID- 15985699
TI  - The selected pathophysiological aspects of PPARs activation.
AB  - Peroxisome proliferator activated receptors (PPARs) belong to a subfamily of
      transcription nuclear factors. Three isoforms of PPARs have been identified:
      alpha, beta/delta and gamma, encoded by different genes and distributed in
      various tissues. They play important roles in metabolic processes like regulation
      of glucose and lipid redistribution. They also have anti-atherogenic, anti
      inflammatory as well as anti-hypertensive functions. In hypertension-induced
      cardiac hypertrophy, both PPARa and PPARg activation reveal cardio-protective
      effect. Despite these beneficial functions, several recent experimental reports
      point to the possibille unfavorable effects of PPARs activation in lipid
      metabolism (lipotoxicity) in cardiomyocytes, which can lead to pathologic cardiac
      hypertrophy in such diseases as diabetes type 2, metabolic syndrome or obesity.
      This paper reviews evidences and hypotheses about the new pathophysiological
      aspects of PPARs activation.

PMID- 15985700
TI  - Superoxide- and nitric oxide-derived species mediate endothelial dysfunction,
      endothelial glycocalyx disruption, and enhanced neutrophil adhesion in the post
      ischemic guinea-pig heart.
AB  - The study was aimed at testing the hypothesis that a toxic product of the
      reaction between superoxide (O(2)(-)) and nitric oxide (NO) mediates, not only
      endothelial dysfunction, but also endothelium-glycocalyx disruption, and
      increased neutrophil (PMN) accumulation in the heart subjected to
      ischemia/reperfusion (IR) injury. Accordingly, we studied if scavengers of either
      O(2)(-) or NO, or a compound that was reported to attenuate cardiac production of
      peroxynitrite, would prevent endothelial injury and subsequent PNM adhesion in IR
      heart. Langendorff-perfused guinea-pig hearts were subjected to 30 min
      ischemia/35 min reperfusion, and infusion of PMN between 15 and 25 min of the
      reperfusion. Coronary flow responses to acetylcholine (ACh) and sodium
      nitroprusside (SNP) were used as measures of endothelium-dependent and 
      independent vascular function, respectively. PMN adhesion and endothelium
      glycocalyx ultrastructure were assessed in histological preparations. IR impaired
      the ACh, but not SNP, response by approximately 60%, caused endothelium
      glycocalyx disruption, and approximately nine-fold increase in PMN adhesion.
      These alterations were prevented by superoxide dismutase (150 U/ml), NO synthase
      inhibitor, L-NAME (10 microM), NO scavenger, oxyhemoglobin (25 microM), and NO
      donor, SNAP (1 microM), and were not affected by catalase (600 u/ml). The
      glycocalyx-protective effect of these interventions preceded their effect on PMN
      adhesion. The data imply that PMN adhesion in IR guinea-pig heart is a process
      secondary to functional and/or structural changes in coronary endothelium, and
      that a toxic product of the reaction between superoxide and NO mediates these
      endothelial changes.

PMID- 15985701
TI  - Hemodynamic and neuroendocrine predictors of lower body negative pressure (LBNP)
      intolerance in healthy young men.
AB  - Exposure to LBNP results in body fluid shift to lower extremities similarly as
      under influence of orthostatic stress. In susceptible persons it leads to
      syncope. For better understanding why certain individuals are more susceptible to
      orthostatic challenges it seemed necessary to collect more data on hemodynamic
      and neuroendocrine adjustments occurring before onset of presyncopal symptoms
      Accordingly, in this study heart rate (HR), blood pressure (BP), stroke volume
      (SV), cardiac output (CO), hematocrit, plasma catecholamines, adrenomedullin,
      ACTH and plasma renin activity (PRA) were measured in 24 healthy men during
      graded LBNP (-15, -30 and -50 mmHg). Thirteen subjects completed the test (HT
      group) whereas 11 had presyncope signs or symptoms at -30 mmHg or at the
      beginning of -50 mmHg (LT group). Comparison of these groups showed that LT
      subjects had lower baseline total peripheral resistance and higher plasma
      adrenomedullin. During LBNP plasma catecholamine and PRA increases were even
      greater in LT than in HT group while plasma adrenomedullin elevations were
      similar in both groups. Plasma ACTH increased only in LT group following
      presyncope symptoms. Low tolerant group showed more rapid decline of SV and CO
      than HT subjects from the beginning of LBNP. It is suggested that measurements of
      SV at the level of LBNP which did not evoke any adverse symptoms may be of
      predictive value for lower orthostatic tolerance.

PMID- 15985702
TI  - Involvement of vagal opioid receptors in respiratory effects of morphine in
      anaesthetized rats.
AB  - Respiratory effects of morphine injection to the femoral vein were investigated
      in urethane and chloralose anaesthetized and spontaneously breathing rats, prior
      to and after midcervical vagotomy. Bolus injection of morphine HCl at a dose of 2
      mg/kg of body weight induced depression of ventilation in all rats, due to the
      significant decrease in tidal volume and to the decline in respiratory rate both
      pre- and post-vagotomy. Expiratory apnoea of mean duration of 10.0+/-3.4 s was
      present in the vagally intact rats only. Bilateral midcervical section of the
      vagus nerve precluded the occurrence of apnoea. Prolongation of the expiratory
      time (T(E morphine) / T(E control)), which amounted to 10.7+/-2.2-fold in the
      intact state, was apparently reduced to 1.5+/-0.3-fold after division of the
      vagi. Morphine significantly decreased mean arterial pressure (MAP) at 30 s after
      the challenge, the effect persisted for not less than 1 minute and was absent in
      vagotomized rats. The respiratory changes evoked by morphine reverted to the
      control level after intravenous injection of naloxone at a dose of 1 mg/kg.
      Results of this study indicate that opioid receptors on vagal afferents are
      responsible for the occurrence of apnoea and hypotension evoked by morphine.

PMID- 15985703
TI  - Blockade of NMDA receptors in postnatal period decreased density of tyrosine
      hydroxylase immunoreactive axonal arbors in the medial prefrontal cortex of adult
      rats.
AB  - Malfunction of glutamatergic neurotransmission in postnatal period is considered
      to be a risk factor for development of schizophrenia. Thus, the present study
      investigates the impact of NMDA receptor blockade in the postnatal period on the
      density of tyrosine hydroxylase immunoreactive axonal arbors in the rat medial
      prefrontal cortex. Behavioral experiments revealed that adult rats (60 days old)
      treated in the postnatal period with a competitive antagonist of NMDA receptors,
      CGP 40116 (1.25 mg/kg on days 1, 3, 6, 9; 2.5 mg/kg on days 12, 15, 18; and
      finally 5 mg/kg on day 21, all injections s.c.), showed enhancement of the
      locomotor activity stimulated by quinpirole (0.3 mg/kg s.c.) and amphetamine (0.5
      mg/kg s.c.), which suggests development of functional supersensitivity of
      dopaminergic systems. It has been found that CGP 40116, given in postnatal period
      decreased the density of tyrosine hydroxylase immunoreactive axonal arbors in the
      medial prefrontal cortex of adult animals. The decrease was observed in
      superficial (II/III) and deep (V/VI) layers of the medial prefrontal cortex,
      while the average length of tyrosine hydroxylase immunoreactive axonal arbors was
      increased in both superficial and deep cortical layers. Changes in the density of
      tyrosine hydroxylase immunoreactive axonal arbors have not been followed by a
      significant decrease in the content of tyrosine hydroxylase protein measured by
      Western blot. Thus, NMDA receptor blockade in the early period of life evokes
      changes in architecture of tyrosine hydroxylase immunoreactive axonal arbors and
      that malfunction of glutamatergic neurotransmission, in early period of life may
      produce anatomical changes which resemble those observed in the brains of
      schizophrenics.

PMID- 15985704
TI  - Open field stress and neurons containing calcium-binding proteins in the piriform
      cortex of the rat.
AB  - In the present study we wanted to check whether the expression of the c-Fos
      protein (the marker of cellular activity) appears in cells containing calcium
      binding proteins (CaBPs) in animals exposed to the open field test. Eight adult
      Wistar rats were examined. In the first step the open field test was applied
      throughout 10 minutes. After perfusional fixation brains were frozen and cut on
      the cryostat in the coronal plane and stained with the standard
      immunohistochemical method. Sections were double stained for c-Fos and CaBPs:
      parvalbumin (PV), calbindin (CB), calretinin (CR). c-Fos positive cells were
      localized predominantly in layers II and III of the piriform cortex (PC). The
      double labeling study showed that neurons containing CaBPs are rarely c-Fos
      immunoreactive. Often PV-positive and CB-positive fibers surround c-Fos-positive
      neurons in layers II and III in a form of a basket. It seems that cells
      containing CaBPs are not directly involved in the response to aversive stimuli
      but cells containing those calcium-binding proteins might influence directly c
      Fos positive neurons of PC.

PMID- 15985705
TI  - Effects of estrone on quisqualate-induced toxicity in primary cultures of rat
      cortical neurons.
AB  - Estrogens exert protective effects against neurotoxic changes induced by over
      activation of ionotrophic glutamate receptors, whereas little is known about
      their interaction with changes mediated by metabotropic glutamate receptors. We
      evaluated effects of estrone on quisqualate (QA)-induced toxicity in neuronal
      cell cultures on 7 and 12 day in vitro (DIV). Twenty four hour exposure to QA
      (150 microM and 300 microM) significantly decreased cell survival in 7 day old
      cultures, but the 12 day old cultures were more resistant to its toxicity. DNQX
      (10 microM), an AMPA/kainate receptor antagonist, partly attenuated the toxic
      effects of QA, whereas LY 367 385 (100 microM), a selective mGluR1a antagonist,
      completely reversed the above effect. QA did not activate, but suppressed
      spontaneous caspase-3-like activity. Estrone (100 nM and 500 nM) attenuated QA
      mediated neurotoxic effects independently of estrogen receptors, as indicated
      with ICI 182, 780 and without affecting the caspase-3-like activity. At early
      stage of development in vitro (7 DIV) toxic effects of QA were more profound and
      mediated mainly by metabotropic glutamate receptors of group I, whereas later (12
      DIV) they were mediated mostly by ionotropic AMPA/kainate receptors. The toxic
      effects of QA were partly accompanied by anti-apoptotic action against
      spontaneous caspase-3-like activity, possibly due to modulation of neuronal
      plasticity.

PMID- 15985706
TI  - Gastric mucin secretion in response to beta-adrenergic G protein-coupled receptor
      activation is mediated by SRC kinase-dependent epidermal growth factor receptor
      transactivation.
AB  - In many systems, the integration of converging regulatory signals that relay on G
      protein-coupled receptor (GPCR) activation into functional cellular pathways
      requires the involvement of receptor tyrosine kinase. In this report, we provide
      evidence that activation of GPCR by beta-adrenergic agonist leading to
      stimulation in gastric mucin secretion requires epidermal growth factor receptor
      (EGFR) participation. Using [(3)H]glucosamine-labeled gastric mucosal cells, we
      show that stimulatory effect of beta-adrenergic agonist, isoproterenol, on mucin
      secretion was inhibited by EGFR kinase inhibitor, PD153035, as well as
      wortmannin, a specific inhibitor of PI3K. Both inhibitors, moreover, blunted the
      mucin secretory responses to beta-adrenergic agonist-generated second messenger,
      cAMP as well as adenylate cyclase activator, forskolin. The gastric mucin
      secretory responses to isoproterenol, furthermore, were inhibited by PP2, a
      selective inhibitor of tyrosine kinase Src responsible for ligand-independent
      EGFR autophosphorylation, but not by ERK inhibitor, PD98059. The inhibition of
      ERK, moreover, did not cause attenuation in mucin secretion in response to cAMP
      and forskolin. The findings underline the role of EGFR as a convergence point in
      gastric mucin secretion triggered by beta-adrenergic GPCR activation, and
      demonstrate the requirement for Src kinase in EGFR transactivation.

PMID- 15985707
TI  - Dynamics of changes in vascular endothelial growth factor (VEGF) expression and
      angiogenesis in stress-induced gastric ulceration in rats.
AB  - Angiogenesis and VEGF play a major role in many repair processes such as healing
      of gastric ulceration. The present study was undertaken to assess the dynamics of
      changes in VEGF expression and angiogenesis in stress-induced gastric ulcers in
      rats. Acute gastric ulceration was induced using a water-immersion and restraint
      stress method. The VEGF expression, angiogenesis, size of area and depth of
      ulcers in gastric specimens were evaluated. The study shows that as early as one
      day after the development of ulcers there is a significant increase in both the
      expression of the VEGF protein and the number of newly formed microvessels, while
      an abrupt decrease in VEGF expression, observed on the fifth day, results in a
      decreased intensity of angiogenesis. Moreover, it has been demonstrated that the
      increase in VEGF expression and angiogenesis is accompanied by a reduction in the
      size of area and depth of stress-induced ulcers in rats. Six days after ulcer
      development both VEGF expression and angiogenesis return to normal levels.

PMID- 15985708
TI  - Synthesis and biological properties of new chimeric galanin analogue GAL(1-13)
      [Ala10,11]ET-1(6-21)-NH2.
AB  - Several chimeric peptides consisting of the N-terminal fragment of galanin (GAL)
      and C-terminal fragments of other bioactive peptides (e.g. substance P,
      bradykinin, neuropeptide Y, mastoparan) have been synthesized and reported as
      high-affinity galanin receptor antagonists. Recently we have synthesized a new
      chimeric peptide, GAL(1-13)-[Ala(10,11)]ET-1(6-21)-NH(2), consisting of the N
      terminal fragment of GAL and the C-terminal fragment of endothelin-1 (ET-1)
      analogue. This chimera was previously shown to be a moderate-affinity ligand to
      hypothalamic galanin receptors with a K(D) value of 205 nM. However, its
      biological action has been unknown so far. In our studies we characterized the
      biological properties of this new chimeric analogue, investigating its action on
      rat isolated gastric smooth muscles and influence on insulin secretion from rat
      isolated islets of Langerhans. Data acquired in the course of our studies suggest
      that analogue GAL(1-13)-[Ala(10,11)]ET-1(6-21)-NH(2) does not seem to be a potent
      galanin receptor antagonist in the gastrointestinal tract.

PMID- 15985709
TI  - Psychosocial stress affects the involvement of prostaglandins and nitric oxide in
      the lipopolysaccharide-induced hypothalamic-pituitary-adrenal response.
AB  - The role of prostaglandins and nitric oxide (NO), generated after peripheral
      lipopolysaccharide (LPS) administration, in the adaptation of hypothalamic
      pituitary-adrenal (HPA) axis under stressful circumstances remains to be
      elucidated. The aim of the present study was to assess the effect of chronic
      repetitive restraint or social crowding stress on the involvement of nitric oxide
      and prostaglandins in the LPS-induced pituitary-adrenocortical response. Male
      Wistar rats were restrained in metal tubes 2 x 10 min/day or crowded in cages for
      7 days prior to treatment. All compounds were injected i.p., cyclooxygenase (COX)
      and nitric oxide synthase (NOS) inhibitors 15 min before LPS. Two hrs after
      injection LPS induced a significant increase in ACTH and corticosterone
      secretion. Repeated restraint impaired more potently than crowding stress the LPS
      induced HPA-response. Indomethacin, a non-selective COX inhibitor, considerably
      reduced the LPS-induced HPA response in non-stressed rats and to a lesser extent
      diminished this response in repeatedly restrained or crowded rats. Neuronal NOS
      inhibitor, Nomega-nitro-L-arginine decreased the LPS-induced HPA response, more
      potently in control than crowded rats. Aminoguanidine, an iNOS inhibitor,
      diminished the LPS-elicited ACTH response in crowded rats. These results indicate
      that prostaglandins and NO generated by neuronal and inducible NOS are involved
      in the LPS-induced HPA axis response under basal conditions and during its
      adaptation to chronic social stress circumstances.

PMID- 15985710
TI  - Endotoxaemia in rats: role of leukocyte sequestration in rapid pulmonary nitric
      oxide synthase-2 expression.
AB  - Nitric oxide (NO), depending on the amount, time and source of generation may
      exert both, protective and deleterious actions during endotoxic acute lung injury
      (ALI). Evaluation of the expression and localization of NOS isoforms in the lung
      of lipopolysaccharide (LPS)-treated rats may contribute to understanding the role
      of NO in pathogenesis of ALI. Tissue samples (lung, heart, liver, kidney and
      spleen) as well as peripheral blood polymorphonuclear cells (PMNs) were collected
      from control male Wistar rats and LPS - treated animals, 15, 30, 60, 120 and 180
      min after LPS injection (2 mg kg(-1) min(-1) for 10 minutes, i.v.). Levels of NOS
      2 and NOS-3 mRNA and protein in tissues and PMNs were estimated by RT-PCR,
      Northern blotting and Western blotting. Additionally, myeloperoxidase (MPO)
      activity in tissue samples was assayed. NOS-3 mRNA as well as protein were
      detected in lungs of control animals; pulmonary NOS-3 expression was not
      influenced by LPS. The induction of NOS-2 mRNA in rat lungs and in PMNs isolated
      from peripheral blood was observed 15 minutes after LPS challenge. In contrast,
      increase of NOS-2 mRNA in the heart, kidneys, liver and spleen was observed 2-3
      hours after LPS injection. In all tissues rise in NOS-2 mRNA was followed after 1
      2 hours by increase of NOS-2 protein. Importantly, progressive leukocyte
      sequestration in the lung parenchyma that started as early as 15 min after LPS
      injection was revealed only in the lungs; in other organs no significant changes
      in MPO activity were detected up to 180 min after LPS injection. In conclusion,
      infusion of LPS caused much more rapid expression of NOS-2 in lungs as compared
      to the heart, kidneys, liver and spleen. Early induction of NOS-2 may depend on
      the LPS-stimulated rapid neutrophil sequestration within lung vasculature and
      fast induction of NOS-2 in sequestrated neutrophils.

PMID- 15985711
TI  - Superoxide dismutase activity and expression in human venous and arterial bypass
      graft vessels.
AB  - Venous bypass grafts are more prone to accelerated atherosclerosis than arterial
      grafts, which is partly related to increased oxidative stress and diminished
      nitric oxide bioavailability. In veins superoxide production is dependent
      primarily on nox2 NAD(P)H oxidase expression, while in arteries nox4 appears to
      play an important role. This may in part explain differences in susceptibility to
      graft failure. Net levels of oxidative stress are however determined in parallel
      by the production as well as by degradation of free radicals (eg. by superoxide
      dismutases, catalases, thioredoxins etc). The differences in superoxide dismutase
      (SOD) expression and activity in human bypass conduit vessels remain unclear.
      Accordingly, we aimed to compare SOD activity and protein levels as well as its
      functional effects on superoxide production in segments of human internal mammary
      arteries (IMA) and saphenous veins (HSV) from patients undergoing bypass graft
      surgery (n=24). SOD activity was assessed by inhibition of pyrogallol
      autoxidation, Cu-Zn SOD and Mn SOD protein levels were studied by immunoblotting.
      Basal superoxide release was detected by lucigenin (5 microM) enhanced
      chemiluminescence. Total SOD activity did not differ significantly between HSV
      and IMA. Similarly, no difference was observed in SOD activity in the presence of
      KCN (Mn-SOD). Human bypass conduit vessels show amounts of Cu-Zn SOD or Mn-SOD
      protein levels. In both HSV and IMA segments superoxide production was more than
      doubled in the presence of SOD inhibitor-DETC. CONCLUSIONS: These studies suggest
      that the differences in oxidative stress between human arteries and veins are
      unlikely to be caused by SOD activity. However SOD plays and important role in
      amelioration of oxidative stress in both types of vessels.

PMID- 15985712
TI  - Neurotoxic action of 6-hydroxydopamine on the nigrostriatal dopaminergic pathway
      in rats sensitized with D-amphetamine.
AB  - To determine whether behavioral sensitization produced by prolonged D-amphetamine
      administration affects susceptibility of nigrostriatal dopaminergic neurons to
      the neurotoxic actions of 6-hydroxydopamine (6-OHDA), rats were treated daily
      from the 23 rd day after birth for 11 consecutive days with D-amphetamine (1.0
      mg/kg s.c.) or saline. On the last day of treatment, one group primed with D
      amphetamine and one control group of rats were tested to confirm behavioral
      sensitization development. The remaining animals were additionally treated on the
      34 th day (one day after the last D-amphetamine injection) with 6-OHDA HBr (300
      microg in 10 microl i.c.v., salt form, half in each lateral ventricle) or its
      vehicle. Four weeks later the levels of dopamine (DA) and its metabolites 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-metoxytyramine (3
      MT), as well as 5-hydroxytrypatmine (5-HT) and its metabolite 5
      hydroxyindoleacteic acid (5-HIAA) were assayed in the striatum, by HPLC/ED. In
      rats with behavioral sensitization, 6-OHDA reduced endogenous dopamine and its
      metabolites content to a comparable degree in comparison to controls. This
      finding indicates that presumed up-regulation of the dopamine transporter in the
      behaviorially sensitized rats did not increase the neurotoxicity of a high dose
      of 6-OHDA.

PMID- 15985713
TI  - Neuroprotective potential of three neuropeptides PACAP, VIP and PHI.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal
      peptide (VIP) and peptide histidine-isoleucine (PHI), are structurally related
      endogenous peptides widely expressed in the central and peripheral nervous system
      and showing rich profile of biological activities. They act as neurotransmitters,
      neuromodulators and neurotrophic factors. Recently, their neuroprotective
      potential has been revealed in numerous in vitro and in vivo models. Thus, PACAP
      and VIP protected the cells from neurotoxic effects of ethanol, hydrogen peroxide
      (H2O2, beta-amyloid and glycoprotein 120 (gp120). Moreover, PACAP showed
      neuroprotection against glutamate, human prion protein fragment 106-126 [PrP(106
      126)] and C2-ceramide. Both peptides reduced brain damage after ischemia and
      ameliorated neurological deficits in a model of Parkinson's disease.
      Neuroprotective potential of PHI has not been thoroughly investigated yet, but
      several results obtained in the last years do not exclude it. The mechanism
      underlying neuroprotective properties of PACAP seems to involve activation of
      adenylyl cyclase (AC) --> cyclic adenosine 3',5'-mono-phosphate (cAMP) -->
      protein kinase A (PKA) and mitogen-activated protein (MAP) kinase pathways, and
      inhibition of caspase-3. PACAP can also, yet indirectly, stimulate astrocytes to
      release neuroprotective factors, such as regulated upon activation normal T cell
      expressed and secreted (RANTES) and macrophage inflammatory protein 1 (MIP-1)
      chemokines. Neuroprotective activity of VIP seems to involve an indirect
      mechanism requiring astrocytes. VIP-stimulated astrocytes secrete neuroprotective
      proteins, including activity-dependent neurotrophic factor (ADNF) and activity
      dependent neuroprotective protein (ADNP), as well as a number of cytokines.
      However, in the activated microglia, VIP and PACAP are capable of inhibiting the
      production of inflammatory mediators which can lead to neurodegenerative
      processes within the brain. In conclusion, studies carried out on the central
      nervous system have shown that PACAP, VIP, and likely PHI, are endowed with a
      neuroprotective potential, which renders them (or their derivatives) promising
      therapeutic agents in several psychoneurological disorders linked to
      neurodegeneration.

PMID- 15985715
TI  - Influence of paraquat on dopaminergic transporter in the rat brain.
AB  - Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a
      parkinsonism inducing compound, is well known to be related to an uptake of its
      active metabolite MPP+ into dopaminergic neurons by dopamine transporter (DAT).
      The aim of the present study was to examine whether paraquat, a commonly used
      herbicide, which is an 1-methyl-4-phenyl-pyridinium ion (MPP+) analogue, affects
      DAT in vivo in rats. Paraquat administered at a dose of 10 mg/kg ip decreased the
      binding of [3H]GBR 12,935 to DAT measured by quantitative autoradiography in the
      dorsal and ventral caudate-putamen, but not in the substantia nigra pars
      compacta. Moreover, this compound increased the level of 3-methoxytyramine (3-MT)
      and 3-MT/dopamine ratio in the anterior and posterior caudate-putamen measured by
      HPLC with electrochemical detection. No other alterations in the levels of
      dopamine and its metabolites were found in the caudate-putamen and substantia
      nigra. The present study seems to suggest that systemic paraquat administration
      affects striatal DAT and dopamine metabolism in the nigrostriatal neurons in rats
      which may be crucial for its neurotoxic effects on dopaminergic neurons.

PMID- 15985714
TI  - Amphetamine-induced effects on neuropeptide Y in the rat brain.
AB  - Repeated (+)-amphetamine sulfate (AMPH) administration (5 mg/kg sc twice daily
      for 6 days and once on day 7) markedly and reversibly decreased (until 96 h after
      the final dose) neuropeptide Y-like immunoreactivity (NPY-LI) in the rat striatum
      (caudate-putamen) and nucleus accumbens, and had no effect on NPY-LI in the
      hippocampus. No significant alterations were detected in the hybridization signal
      of NPY mRNA4 and 24 h after the end of AMPH treatment. A single dose of AMPH (5
      mg/kg sc) administered to rats 4 and 24 h prior to sacrifice had no effect on NPY
      LI in the brain structures studied. Moreover, AMPH injected 8 days after the last
      dose of repeated AMPH administration did not change NPY-LI up to 72 h. The
      minimal dose of haloperidol, the strong mixed dopaminergic D2/D1 receptor
      antagonist, (0.75 mg/kg injected ip 30 min before each of the multiple AMPH
      administrations) that was sufficient to completely block stereotypy and
      hyperlocomotion elicited by multiple AMPH administrations enhanced the AMPH
      induced decrease in the striatal and accumbens NPY-LI. Our results suggest that
      NPY neurons in the striatum, nucleus accumbens and hippocampus are not directly
      involved in the acute behavioral response to AMPH (stereotypy and
      hyperlocomotion) as well as in the initiation and expression of AMPH-induced
      behavioral sensitization.

PMID- 15985716
TI  - Synthesis, anticonvulsant properties and 5-HT1A/5-HT2A receptor affinity of new N
      [(4-arylpiperazin-1-yl)-propyl]-2-aza-spiro[4.4]nonane and [4.5]decane-1,3-dione
      derivatives.
AB  - A series of twenty new N-[(4-arylpiperazin-1-yl)-propyl]-2-aza-spiro[4.4]nonane-
      and [4.5]decane-1,3-dione derivatives were synthesized and their anticonvulsant
      activity was evaluated in maximal electroshock (MES) and sc pentertazole (sc PTZ)
      tests. Their neurotoxicity was examined as well. Although no antiseizure
      properties of the investigated compounds were found in the MES model, eight of
      them were active in the sc PTZ test and three, namely 2-{3-[4-(2-fluorophenyl)
      piperazin-1yl]-propyl}-2-aza-spiro[4.4]nonane-1,3-dione (7), 2-{3-[4-(2
      fluorophenyl)-piperazin-1-yl]-propyl}-7-methyl-2-aza-spiro[4.5]-decane-1,3- dione
      (22) and 2-{3-[4-(3-chlorophenyl)-piperazin-1-yl]-propyl}-7-methyl-2-aza
      spiro[4.5]-decane-1,3-dione (23) were classified to the Anticonvulsant Screening
      Program (ASP) 1 class. In addition, since the investigated compounds belong to a
      class of long-chain arylpiperazines, their serotonin 5-HT1A and 5-HT2A receptor
      affinity was determined. All the 2-OCH3 and 3-Cl derivatives were the most potent
      5-HT1A receptor ligands (Ki = 24-143 and 70-107 nM, respectively), whereas the
      highest 5-HT2A affinity was observed for the unsubstituted and 3-Cl derivatives
      (Ki = 8-66 nM). No correlation between anticonvulsant and serotonergic activity
      was observed.

PMID- 15985717
TI  - Effect of cysteamine on bile secretion in the rat.
AB  - The effect of cysteamine, a specific somatostatin depletor, on biliary secretion
      was studied in urethane-anesthetized rats. Different groups of rats received ip
      cysteamine at 25, 100 or 340 mg/kg just before bile collection commenced. Other
      groups of rats were pretreated with cysteamine (340 mg/kg ip) at 4 or 24 h prior
      to bile duct cannulation and bile collection. Bile secretions were collected at
      30-min intervals for 4 h after bile duct cannulation. Total proteins,
      cholesterol, total lipids, glucose and several hepatic enzymes were assessed in
      bile. Results indicated that basal bile secretion was only slightly reduced and
      tended to decrease after drug administration (13% decrease after 340 mg/kg).
      Cysteamine induced dose-dependent decrease in protein secretion, and the maximum
      effect was reached at a dose of 340 mg/kg. The effect of cysteamine on protein
      secretion was prolonged, since it was still observed 24 h after the treatment
      with cysteamine. Cholesterol and lipid secretion was inhibited by 52.5 and 42.5%,
      respectively, by the drug, with the latter effect being evident 24 h after drug
      administration. In addition, the drug inhibited biliary glucose and aspartate
      aminotransferase concentrations, but increased that of alkaline phosphatase. The
      results suggest that acute administration of cysteamine inhibits protein,
      cholesterol and lipid secretion into bile.

PMID- 15985718
TI  - Differential effects of genistein, estradiol and raloxifene on rat osteoclasts in
      vitro.
AB  - Genistein, a major phytoestrogen of soy, is considered a potential drug for
      prevention and treatment of postmenopausal osteoporosis. It is not clear whether
      mechanism of action of genistein on bone turnover is distinct from that of
      estradiol or raloxifene. The aim of the present study was to investigate the
      effects of genistein on the formation of osteoclasts from neonatal rat bone
      marrow cells in vitro, and compare them with those of estradiol and raloxifene.
      Formation of osteoclasts was stimulated by 1,25-dihydroxyvitamin D3, added to the
      culture media on the second day after plating, together with genistein (10(-8)
      10(-5) M), estradiol (10(-10)-10(-7) M) or raloxifene (10(-9)-10(-6) M). The bone
      marrow cell culture lasted 7 or 9 days. Number of osteoclasts and number of
      osteoclast "ghosts" (necrotic giant cells) were determined. Genistein, estradiol
      and raloxifene, at some concentrations, decreased the number of osteoclasts after
      9-day culture of bone marrow cells. Genistein decreased the number at 10(-8) M
      because of decreasing the viability of osteoclasts, whereas at 10(-5) M due to
      attenuation of osteoclast formation. Estradiol decreased the osteoclast number at
      10(-9) M due to decreasing their viability, whereas at 10(-8) and 10(-7) M it was
      the effect of both decreasing the viability and inhibition of the formation.
      Decreases in the number of osteoclasts caused by raloxifene (10(-9), 10(-8) M
      were the effect of decreasing the viability of these cells.

PMID- 15985719
TI  - Induction of caspase 3 activity, bcl-2 bax and p65 gene expression modulation in
      human acute promyelocytic leukemia HL-60 cells by doxorubicin with amifostine.
AB  - The influence of amifostine alone and in combination with doxorubicin,
      cytarabine, and etoposide on the cell growth and on bcl-2, bax and p65 gene
      expression was investigated in human acute promyelocytic leukemia cell line HL
      60. No or very little influence of the exposure of HL-60 cells to amifostine (10(
      6) to 10(-2) M) on cell proliferation was shown. Proliferation of HL-60 cells
      exposed to doxorubicin, cytarabine, or etoposide dropped down with increasing
      doses of these drugs. Only in the case of doxorubicin, more effective inhibition
      of HL-60 cell growth was observed when combination of doxorubicin, cytarabine or
      etoposide with amifostine was used. Cytotoxic effect of cytarabine or etoposide
      was not reduced by amifostine. The lowering of the cytotoxic index (IC50) was
      observed only when HL-60 cells were preincubated with amifostine followed by
      doxorubicin treatment. IC50 was estimated as 2.1 x 10(-7) M and 0.9 x 10(-7) M
      for doxorubicin and doxorubicin with amifostine, respectively. This effect was
      accompanied by the induction of caspase 3 activity. HL-60 cells treated with
      doxorubicin alone showed about 35-fold increase in caspase 3 activity. The enzyme
      activity was stimulated by combination of doxorubicin with amifostine up to 94
      times. Furthermore, the expression of bcl-2 and bax genes involved in apoptosis
      as well as tumor-associated p65 gene were determined. Semiquantitative reverse
      transcriptase polymerase chain reaction showed a decrease in bcl-2 and an
      increase in bax and p65 expression in HL-60 cells treated with doxorubicin in
      combination with amifostine when compared with the cells treated only with
      doxorubicin. Amifostine may potentiate doxorubicin therapeutic efficiency in
      human acute promyelocytic leukemia cells.

PMID- 15985720
TI  - Monocyte suppressing action of fenofibrate.
AB  - Since atherosclerosis has been proven to be an inflammatory disease, it is
      obvious that the proper treatment for dyslipidemia should not only correct lipid
      parameters but also inhibit inflammation. Monocytes and monocyte-derived
      proinflammatory cytokines are widely known to be involved in the formation and
      rupture of the atherosclerotic plaque. The aim of our study was to assess the
      effect of fenofibrate, a commonly used hypolipidemic drug, on the release of
      interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and monocyte chemoattractant
      protein 1 (MCP-1) by monocytes from patients with combined hyperlipidemia.
      Fourteen patients with biochemically confirmed type IIb dyslipidemia who did not
      respond to a low-fat diet were treated with micronized fenofibrate for 1 month.
      The control group included 12 healthy, normolipidemic, age-matched subjects. To
      accurately evaluate the levels of the inflammatory cytokines, we excluded
      patients with any inflammatory disease. Monocytes were isolated from peripheral
      blood before and after the treatment. IL-1beta, IL-6 and MCP-1 release was
      measured by enzyme-linked immunosorbent assay (ELISA) after lipopolysaccharide
      stimulation. IL-1beta, IL-6 and MCP-1 levels were significantly higher in
      hyperlipidemic patients compared to the control (143.9 +/- 6.5 vs. 74.4 +/- 4.4
      pg/ml; 8212 +/- 285 vs. 6110 +/- 170 pg/ml; 19.6 +/- 0.9 vs. 12.3 +/- 0.6 ng/ml,
      respectively). Thirty-day fenofibrate treatment decreased the release of IL-1beta
      by 43% (143.9 +/- 6.5 vs. 86.2 +/- 5.9 pg/ml), of IL-6 by 22% (8212 +/- 285 vs.
      6330 +/- 234 pg/ml), and of MCP-1 by 29% (19.6 +/- 0.9 vs. 14.0 +/- 0.8 ng/ml).
      The evaluated cytokines were markedly elevated in patients with type IIb
      dyslipidemia. Effective fenofibrate therapy had a significant inhibitory effect
      on the release of monocyte-derived inflammatory cytokines.

PMID- 15985721
TI  - Effects of some convulsant agents on the protective activity of topiramate
      against maximal electroshock-induced seizures in mice.
AB  - The anticonvulsant activity of topiramate combined with some convulsant agents
      (bicuculline--BIC, N-methyl-D-aspartate--NMDA, and kainic acid--KA), given at
      subconvulsive doses, was evaluated in the maximal electroshock (MES)-test in
      mice. BIC (1.5 mg/kg), KA (10 mg/kg) and NMDA (50 mg/kg) significantly decreased
      the anticonvulsant activity of topiramate raising its ED(50) from 76.2 mg/kg to
      135, 102, and 107 mg/kg, respectively. BIC (0.75 mg/kg) and KA (5 mg/kg) did not
      alter the protective activity of topiramate in the MES-test. Moreover, topiramate
      injected alone (up to 135 mg/kg) did not affect motor performance and long-term
      memory of animals tested in the chimney and passive avoidance tests,
      respectively. In contrast, combinations of topiramate with BIC (1.5 mg/kg), NMDA
      (50 mg/kg) or KA (10 mg/kg) considerably disturbed long-term memory in mice.
      Additionally, co-administration of topiramate with KA (10 mg/kg) or BIC (1.5
      mg/kg) significantly impaired motor performance, whereas topiramate co
      administered with NMDA (50 mg/kg) had no impact on motor coordination in mice.
      None of the studied convulsants affected the free plasma concentration of
      topiramate assayed with immunofluorescence method. The results of this study seem
      to indicate the expression of the anticonvulsant activity of topiramate is
      dependent on all ionotropic glutamate and GABAA receptor-mediated events.

PMID- 15985722
TI  - Effect of licofelone against mechanical hyperalgesia and cold allodynia in the
      rat model of incisional pain.
AB  - Hyperalgesia from an incisional pain is evoked by noxious stimuli (mechanical and
      cold). The present study was aimed to examine the effect of licofelone, a dual
      inhibitor of cyclooxygenases (COX-1/COX-2) and 5-lipoxygenase (5-LOX) against
      mechanical hyperalgesia and cold allodynia in the rat model of incisional pain.
      Mechanical hyperalgesia and cold allodynia was assessed employing Randall and
      Sellitto analgesymeter and cold water maintained at 10 degrees C, respectively.
      Zileuton (25-100 mg/kg, po), a 5-LOX inhibitor, indomethacin (1-30 mg/kg, po), a
      non-selective COX inhibitor, and licofelone (10-100 mg/kg, po) a dual inhibitor,
      significantly reversed the mechanical hyperalgesia and also caused an increase in
      cold allodynia threshold with different pharmacologic profile. The rank order of
      potency based on ED50 values in both the paradigms was found to be licofelone >
      indomethacin > zileuton. The results of the present study are indicative of the
      role of leukotrienes along with prostaglandins in the rat model of incisional
      pain (a paradigm of postoperative pain). The results suggested that dual
      inhibition approach of simultaneous inhibition of COX and LOX pathways might
      prove beneficial in combating hyperalgesia of postoperative pain.

PMID- 15985723
TI  - Acute effect of ethanol on IgA immunoreactive cells in the intestine-associated
      immune system.
AB  - The purpose of this study was to investigate the acute effect of ethanol on
      mucosa-associated lymphoid tissue at the level of Peyer's patches and the
      intestinal lamina propria in female rats and to determine whether this action of
      ethanol is modulated during the estrous cycle. Adult female rats showing
      proestrus or diestrus day 1 were treated intraperitoneally (ip) with ethanol (4
      g/kg). Untreated and saline-injected rats were used as controls. The animals were
      sacrificed by decapitation 0.5 h after ethanol administration. Immunoglobulin A
      (IgA) immunoreactive cells were analyzed by indirect immunohistochemistry using
      mouse anti-rat IgA and a Dako LSAB+ kit. The number of IgA-immunoreactive cells
      in Peyer's patches was unaltered by ethanol treatment at both phases of the
      estrous cycle. However, stereological analysis revealed a significant increase in
      the number of IgA-immunoreactive cells (p < 0.01) in the intestinal lamina
      propria following acute ethanol administration at proestrus and on diestrus day
      1. The results indicate that the intestinal lamina propria, the effector site of
      the mucosal immune system, can be affected by a single dose of ethanol at both
      phases of the estrous cycle.

PMID- 15985725
TI  - Molecular Basis for Signal Transduction in Neurodegeneration and
      Neuroregeneration. Abstracts of the 20th Biennal Meeting of the ISN Satellite
      Symposium, August 27-30, 2005, Warszawa, Poland.

PMID- 15985724
TI  - Effect of apigenin, kaempferol and resveratrol on the expression of interleukin
      1beta and tumor necrosis factor-alpha genes in J774.2 macrophages.
AB  - Flavonoids have been reported to bring benefits in lowering inflammation,
      oxidative stress and exert positive effects in cancer and cardiovascular and
      chronic inflammatory diseases. Apigenin, kaempferol and resveratrol present in
      fruits, vegetables and grain were investigated for their effect on the synthesis
      of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) at
      transcriptional level in lipopolysaccharide (LPS)-stimulated J774.2 macrophages.
      Apigenin (30 microM), kaempferol (30 microM) and resveratrol (50 microM)
      significantly decreased the number of TNF-alpha mRNA copies in LPS-activated
      J774.2 macrophages. Apigenin and kaempferol caused inhibition of IL-1beta gene
      expression in J774.2 macrophages, but resveratrol was ineffective. These results
      indicate that apigenin, kaempferol and resveratrol exert inhibitory effects on
      the TNF-alpha and except for of resveratrol on IL-1beta gene expression in J774.2
      macrophages at the transcriptional level. In addition, the studied compounds may
      be the mediators responsible for protective role of a diet high in fruits and
      vegetables in the cardiovascular and inflammatory diseases.

PMID- 15985726
TI  - Usefulness of CD45 density in the diagnosis of B-cell chronic lymphoproliferative
      disorders.
AB  - BACKGROUND: Although many B-cell chronic lymphoproliferative disorders (BCLPDs)
      including B-cell chronic lymphocytic leukemia (B-CLL) have characteristic
      clinical and biological features, the overlapping morphologic and
      immunophenotypic profiles of various BCLPDs, is still the main problem. AIM: Our
      aim was to evaluate the usefulness of CD45 expression in the immunological
      classification of BCLPDs. SETTING AND DESIGN: A prospective study was set in a
      university hospital to investigate the CD45 intensity, particularly in B-CLL.
      MATERIALS AND METHODS: The expression of CD45 in 37 patients with BCLPD including
      typical B-CLL (Group I), atypical B-CLL and CLL/PLL (II), and hairy cell leukemia
      (HCL), B-prolymphocytic leukemia (B-PLL), and B-non Hodgkin's lymphoma (B-NHL) as
      non-CLL BCLPDs (III) and in eight healthy age matched controls (IV) was
      quantitatively compared by flow cytometric CD45/RALS gating strategy. STATISTICAL
      ANALYSIS: The mean, median, and peak channel scores of CD45 obtained for the four
      groups were compared using one-way analysis of variance test. A P value RESULTS:
      Lower CD45 density is associated highly with typical CLL and differences between
      typical CLL and other groups were significant (P< 0.001, 0.001, and 0.001). Non
      CLL cases had significantly brighter CD45 expression than atypical CLL (P=0.014).
      No differences were found between normal lymphocytes and non-CLL BCLPD cases.
      CONCLUSIONS: CD45 is a useful marker, to discriminate the typical CLL from the
      non-CLL BCLPD and from atypical CLL.

PMID- 15985727
TI  - Domestic violence in pregnancy in North Indian women.
AB  - BACKGROUND: Domestic violence against pregnant women in the Indian context,
      violence against women is frequently by family members other than the
      spouse/intimate partner/husband. AIMS: To study the incidence of domestic
      violence in pregnant North Indian women and the demographic features which put
      women at high risk for domestic violence. STUDY DESIGN: A prospective study at
      the Government Medical College and Hospital, Chandigarh from January 2004 to
      December 2004. PARTICIPANTS: Nine hundred and ninety-one pregnant women admitted
      to the pregnant women admitted to the antenatal ward were interviewed.
      STATISTICAL ANALYSIS: Test of significance used was Chi-square test. Odds ratio
      (OR) and 95% confidence interval (CI) was calculated. RESULTS: The incidence of
      domestic violence in this study was 28.4%. The violence was more when the husband
      was educated up to Class 10 level or lower (OR 2.07 (95%) CI 1.54 to 2.79), was
      habituated to alcohol (OR 2.31 (95%) CI 1 - 71 to 3.11) or to chewing tobacco (OR
      2.77 (95%) CI 1.46 to 3.27) or to smoking cigarettes (OR 2.23 (95%) CI 1.59 to
      3.11). The incidence of domestic violence was drastically high in women who were
      socially unsupported (OR 98.9 (95%) CI 43.65 to 235.68). The level of education
      and employment of the woman had no effect on the incidence of the abuse. The
      perpetrator of the abuse was the intimate partner (husband) in 48.2%, the
      husband's mother in 61.3%, and the husband's sister in 22.6%. Most often the
      abuse was by more than one person. CONCLUSIONS: The incidence of abuse was more
      when the male partner was less educated or in the habit of taking alcohol, opium
      or tobacco and in socially unsupported women. The level of education and
      employment of the woman had no effect on the incidence of abuse.

PMID- 15985728
TI  - Indigenous recombinant streptokinase vs natural streptokinase in acute myocardial
      infarction patients: Phase III multicentric randomized double blind trial.
AB  - BACKGROUND: Streptokinase is the most widely used thrombolytic agent and can now
      be made using recombinant DNA technology. The present trial was initiated to
      assess an indigenous recombinant streptokinase (Shankinase, r-SK). AIM: To
      compare the efficacy and safety of indigenous recombinant streptokinase
      (Shankinase, r-SK) and natural streptokinase (Streptase, n-SK). SETTINGS AND
      DESIGN: Double blind, randomized, non-inferiority, multicentric, parallel study.
      MATERIALS AND METHODS: Patients of AMI < 6 hours of chest pain and 2 mm ST
      elevation in 2 contiguous chest leads V(1)-V(6) or 1 mm in limb leads were
      randomized to receive 1.5 miu of either r-SK or n-SK. CK Peaking and decrease of
      > or = 50% ST segment were used to assess reperfusion. STATISTICAL ANALYSIS:
      Difference in the groups was assessed by chi-square or paired t test as required.
      Probability value < 0.05 was considered significant with 95% confidence interval.
      RESULTS: Overall 150 patients were recruited (96 r-SK group and 54 in n-SK group)
      and demographic and clinical profile of the groups was comparable. Reperfusion
      was seen in 68.2% (58) and 69.4% (34) patients in r-SK and n-SK groups
      respectively. Commonly seen adverse events were fever in 7 (8.5%), hypotension in
      3 (3.6%), nausea in 2 (2.4%) patients. Minor bleeding were seen in 4 (4.8%) of
      patients. CONCLUSION: Indigenous recombinant Streptokinase (r-SK) is as
      efficacious as natural streptokinase (n-SK) in establishing reperfusion as
      assessed by non-invasive parameters with comparable side effect profile.

PMID- 15985729
TI  - Magnetic resonace appearance of gall bladder ascariasis.
AB  - Ascariasis is a common disease in many developing countries and is a common cause
      of biliary and pancreatic diseases in endemic areas. Numerous studies have been
      published on biliary tract ascariasis. All these have documented ultrasonography
      as the primary imaging modality for biliary tract ascariasis. Magnetic Resonance
      Cholangiopancreatography (MRCP) has been the latest entrant for the study of
      bilary tract. MRCP findings of biliary tract ascariasis have been scarcely
      documented. MRCP is a unique non-invasive investigation for demonstrating
      ascariasis in gall bladder and bilary tract clearly. We present MR appearances of
      gall bladder and biliary tract in a proven case of biliary ascariasis.

PMID- 15985730
TI  - Cutaneous markers in ochronosis.

PMID- 15985731
TI  - Pleural empyema due to group a beta-hemolytic streptococci in an adult.

PMID- 15985732
TI  - Gentamicin resistance in biofilm producing Pseudomonas aeruginosa causing
      catheter associated urinary tract infections.

PMID- 15985733
TI  - Diagnosis of depression in general practice.
AB  - Depression is well recognized as a public health problem that usually runs the
      risk of becoming chronic, disabling and life threatening if left untreated.
      Unfortunately depression remains largely under diagnosed in primary care although
      more than one in ten cases seen in primary care suffers from this condition.
      Primary care physicians are strategically placed to detect and treat depression
      early and thus contribute in secondary prevention of this disorder. This article
      highlights the problems in diagnosis, the ways depressed patients present to the
      clinicians, the diagnostic criteria, the detailed interview techniques to arrive
      at a diagnosis of depression. The article also offers an outline of management of
      depression in primary care.

PMID- 15985734
TI  - Non traumatic coma.
AB  - OBJECTIVE: To study the etiology and clinical profile of non-traumatic coma in
      children and to determine the clinical signs predictive of outcome. METHODS: 100
      consecutive cases of non-traumatic coma between 2 months to 12 years. Clinical
      signs studied were temperature, pulse, heart rate, blood pressure, coma severity
      by Glasgow coma scale (GCS), respiratory pattern, pupillary and corneal reflex,
      extra ocular movements, motor patterns, seizure types and fundus picture. These
      were recoded at admission and after 48 hours of hospital stay. Etiology of coma
      was determined on basis of clinical history, examination and relevant laboratory
      investigations by the treating physician. The outcome was recorded as survived or
      died, and among those who survived as normal, mild, moderate, or severe
      disability. Chi-square test and logistic regression analysis were done to
      determine predictors of outcome. RESULTS: Etiology of coma in 60% cases was CNS
      infection (tubercular meningitis-19, encephalitis-18, bacterial meningitis-16,
      others-7); other causes were toxic-metabolic conditions (19%), status epilepticus
      (10%), intracranial bleed (7%), and miscellaneous (4%). 65 children survived, 11
      were normal, 14 had mild disability, 21 had moderate disability and 14 were
      severely disabled and dependent. Survival was significantly better in patients
      with CNS infection (63%) as compared to those with toxic-metabolic causes (27%)
      and intracranial bleed (43%, P < 0.05). On bivariate analysis age < or = 3 years,
      poor pulse volume, abnormal respiratory pattern and apnoea, abnormal pupillary
      size and reaction, abnormal extra ocular movements, absent corneal reflex,
      abnormal motor muscle tone at admission or 48 hours correlated significantly with
      mortality. Survival was better with increasing GCS (Spearman rho = .32, P <
      0.001). On logistic regression age < 3 years, poor pulse volume, absent
      extraocular movements and papilloedema at admission and 48 hours after admission
      were independent significant predictors of death. CONCLUSION: CNS infections were
      the most common cause of non-traumatic coma in childhood. Simple clinical signs
      were good predictors of outcome.

PMID- 15985735
TI  - Predictive value of electroencephalography and computed tomography in childhood
      non-traumatic coma.
AB  - OBJECTIVES: To study value of electroencephalogram (EEG) and computed tomography
      (CT Scan) in predicting outcome of non-traumatic coma in children. METHODS: 100
      consecutive children, between 2 months to 12 years, with non-traumatic coma,
      (Glasgow Coma Scale score < 8). Demographic and clinical data was recorded at
      admission. EEG and CT scan were done within 24 hours of admission. Etiologic
      diagnosis was assigned on basis of clinical data and relevant laboratory
      investigations. The outcome was recorded as survived and died. Among survivors it
      was graded as no disability, or mild, moderate, or severe disability. Odds ratio
      and/or relative risk (RR) with 95% confidence interval (C I) were calculated.
      RESULTS: EEG could be done in 60 patients (43 survived; 7 were normal, 8 had
      mild, 17 moderate and 11 severe disability) CT scan in 93 patients (60 survived;
      11 were normal, 14 had mild, 21 moderate and 14 severe disability). A
      normal/borderline EEG was associated with good outcome (P = 0.001); 11 of 12
      survived and of survivors 55% had no or mild disability. Electrocerebral silence
      on EEG was a predictor of death (OR = 44 -sub .95% Cl - 1.5-7372; P = 0.01). An
      abnormal EEG was associated with significant increase in risk of disability among
      survivors (RR = 2.6, 95% Cl = 1.2-5.4, P = 0.03). Among CT abnormalities
      intracranial bleed suggested increased risk of death (RR = 2.1; 95% Cl - 0.8-5.3;
      P = 0.058), while, hydrocephalus was associated with better survival (RR = 0.7;
      95% CI - 0.5 to 0.96; P = 0.029). However, hydrocephalus when compared with other
      abnormal CT scan findings, was associated with higher risk of moderate and severe
      disability among survivors (P = 0.046) CONCLUSION: A normal CT scan and EEG, and
      some of the specific findings could be helpful in predicting outcome in children
      with non-traumatic coma. EEG and CT scan should be done at admission in all
      patients with non-traumatic coma if feasible.

PMID- 15985736
TI  - Economic disparity and child nutrition in Bangladesh.
AB  - OBJECTIVE: The aim of this study was to assess the economic difference in
      nutrition of under-five children. METHODS: Bangladesh Demographic Health Survey
      data 1999-2000 were used for this study. In this study, quintiles were calculated
      on the basis of asset and wealth score by use of principal component analysis. To
      understand the nutrition status and health inequality concentration index was
      also calculated. RESULTS: The ratio of poorest to the richest indicates that
      stunting and underweight of the rural under-five children was almost two times
      higher than that of the richest children. The negative concentration index shows
      that higher rate of malnutrition among the under-five children from the poorest
      class. This inequality in health situation of the children can be explained in
      terms of income inequality. In Bangladesh, about 40% wealth is concentrated to
      10% of the families. The results are discussed in terms of policy consideration.
      CONCLUSION: It is expected that the findings will lead to consider alternative
      program strategies for the reduction of poor nutritional status of the children
      and their mothers.

PMID- 15985737
TI  - Birth defects surveillance study.
AB  - OBJECTIVE: To study the overall frequency of congenital malformations in a city
      hospital in the first three days of life. METHODS: 17,653 consecutive newborns
      were examined and diagnosed at a maternity hospital by pediatricians and
      geneticists. Relevant information was documented on a predesigned proforma and
      analyzed. RESULTS: Of the 17,653 births 294 (1; 6%) had major malformations and
      1400 (7.92%) had minor malformations. Amongst 17,653 births 328 (1.8%) were
      stillbirths. Malformations were highest in this group. Polygenic traits accounted
      for 45.1% while chromosomal etiology was found in 4%. A genetic basis was found
      in 65.4% of cases. CONCLUSION: With emphasis on ''small family '' norms &
      population control it is necessary to identify malformations so that
      Interventional programmes can be planned.

PMID- 15985739
TI  - Diagnosis and management of acyanotic heart disease: part I -- obstructive
      lesions.
AB  - In this review, the clinical features and management of most commonly encountered
      acyanotic obstructive cardiac lesions are discussed. Mild lesions, especially in
      children are usually asymptomatic while neonates and infants may present with
      symptoms. Ejection systolic murmurs in patients with pulmonic and aortic stenosis
      and decreased femoral pulses and blood pressure difference (>20 mmHg) between
      arms and leg in patients with aortic coarctation are usually seen. Clinical
      diagnosis is not difficult and the diagnosis can be confirmed and quantitated by
      non-invasive echocardiographic studies. Whereas surgical intervention was used in
      the past, balloon dilatation appears to be effective in the treatment of these
      lesions.

PMID- 15985740
TI  - Diagnosis and management of acyanotic heart disease: part II -- left-to-right
      shunt lesions.
AB  - In this review, the clinical features and management of most commonly encountered
      acyanotic, left-to-right shunt lesions are discussed. Patients with small
      defects, especially in childhood, are usually asymptomatic while moderate to
      large defects in infancy may present with symptoms. Hyperdynamic precordium,
      widely split and fixed second heart sound, ejection systolic murmur at the left
      upper sternal border and a mid-diastolic flow rumble at the left lower sternal
      border are present in atrial septal defects, holosystolic murmur at the left
      lower border is characteristic for a ventricular septal defect whereas a
      continuous murmur at the left upper sternal border is distinctive for patent
      ductus arteriosus. Clinical diagnosis is not usually difficult and the diagnosis
      can be confirmed and quantitated by non-invasive echocardiographic studies.
      Whereas surgical intervention was used in the past, transcatheter methods are
      increasingly used for closure of atrial septal defect and patent ductus
      arteriosus. Small ventricular septal defects may not need to be closed whereas
      medium and large defects may require surgical closure. Transcatheter closure of
      both muscular and membranous ventricular septal defects is feasible by
      transcatheter methodology, but these techniques are experimental at the time of
      this writing.

PMID- 15985741
TI  - Pediatric cardiology for the primary care pediatrician.

PMID- 15985742
TI  - Univentricular heart: management options.
AB  - The term ''Univentricular Heart'' encompasses a wide variety of heart defects
      that functionally and physiologically constitute a single ventricular chamber.
      The terminology ''univentricular repair'' is frequently used in the surgical
      literature to include those biventricular hearts that are not amenable for a
      final two ventricle repair and need to go through the same surgical stages as
      with a functionally univentricular heart, culminating finally in a total cavo
      pulmonary connection. Broadly, treatment is focused on controlling the pulmonary
      blood flow in early infancy, by means of aorto-pulmonary shunting in pulmonary
      atresia or stenosis, and pulmonary artery banding or pulmonary artery
      disconnection with aorto-pulmonary shunt placement in high pulmonary blood flow
      situations. Concomitant repair of other associated conditions is required. Babies
      with hypoplastic left heart physiology undergo staged "Norwood" repair resulting
      in an eventual total cavo-pulmonary connection with the RV functioning as the
      systemic ventricle. In this review, medical and surgical management of these
      patients will be discussed, after a brief discussion of nomenclature, anatomic
      and physiologic considerations.

PMID- 15985743
TI  - Anotia and facial palsy: unusual features of cardiofacial syndrome.
AB  - The authors report a child with features of Cardiofacial syndrome with anotia and
      facial paralysis. This is the first report of such an association.

PMID- 15985744
TI  - Nephrogenic diabetes insipidus presenting with developmental delay and
      intracranial calcification.
AB  - A one-year-boy presented with constipation, fever, failure to thrive and
      developmental delay from the neonatal period. Investigations revealed persistent
      hypernatremia and deranged renal functions. Diagnostic work-up was suggestive of
      nephrogenic diabetes insipidus (NDI). Computerized tomography of head revealed
      calcification in the frontal, thalamic and basal ganglia region. The rare
      association of NDI and intracranial calcification is discussed.

PMID- 15985745
TI  - Recurrent postictal depression with Cotard delusion.
AB  - Depression is a common occurrence among epileptic patients and constitutes, along
      with anxiety disorders, the most frequent psychiatric condition in these
      patients. However, little work is done in the area of post-ictal depression
      especially in children with epilepsy. Here, the authors report an adolescent boy
      who developed recurrent depression associated with Cotard's delusion following
      complex partial seizure at the age of 7 years. Trial of antidepressant drug and
      lithium worsened the clinical picture but ultimately he responded well to
      carbamazepine. This case is unique in its presentation due to recurrent
      depression itself is rare at this age and secondly rarity of onset of Cotard
      delusion in prepubertal phase. This case also showed that post-ictal depression
      is biological process rather than psychological and social reaction. Prompt
      identification and management of underlying cause would definitely prevent
      further complication and would also prevent the child from exposing unnecessary
      with various pharmacological treatments.

PMID- 15985746
TI  - Transfusion associated GVHD.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is an under-diagnosed
      condition in clinical practice. It can occur in immunocompromised as well as
      immunocompetent hosts and may follow allogeneic bone marrow transplant or
      transfusion from a related donor. The clinical course is stormy with a high
      mortality rate. Avoiding the use of blood transfusions from related donors and
      irradiation of blood products can prevent graft versus host disease. A case of
      graft versus host disease following related donor transfusion is presented here.

PMID- 15985747
TI  - Major hemoptysis in adolescents.
AB  - The coughing up of blood or blood-tinged sputum in children is unusual but
      potentially lethal. The etiologies of hemoptyses in children differ from adults
      and vary among geographic locations. This paper reviews the clinical presentation
      and radiographic features of massive hemoptysis in adolescents seen in a single
      tertiary children's hospital in northern Taiwan during a 10-year period. Active
      pulmonary tuberculosis with cavity formations and dissemination, congenital heart
      diseases with hypertrophied bronchial artery and local bleeding were the 2 most
      common causes of major hemoptysis in this single institute experience. Most cases
      of major hemoptysis due to active pulmonary tuberculosis can be managed
      conservatively. For patients with respiratory compromise or hemodynamic
      instability, selective bronchial artery embolization effectively stopped
      hemoptysis without complications.

PMID- 15985748
TI  - Esophageal atresia.

PMID- 15985750
TI  - Genetic disorders of surfactant homeostasis.
AB  - Adaptation to air breathing at birth requires the precise orchestration of
      cellular processes to initiate fluid clearance, enhance pulmonary blood flow, and
      to synthesize and secrete pulmonary surfactant needed to reduce surface tension
      at the air-liquid interface in the alveoli. Genetic programs regulating the
      synthesis of the surfactant proteins and lipids required for the production and
      function of pulmonary surfactant are highly conserved across vertebrates, and
      include proteins that regulate the synthesis and packaging of pulmonary
      surfactant proteins and lipids. Surfactant proteins B and C (SP-B and -C) are
      small, uniquely hydrophobic proteins that play important roles in the stability
      and spreading of surfactant lipids in the alveolus. Deletion or mutations in SP-B
      and -C cause acute and chronic lung disease in neonates and infants. SP-B and -C
      are synthesized and packaged with surfactant phospholipids in lamellar bodies.
      Normal lamellar body formation requires SP-B and a member of the ATP-binding
      cassette (ABC) family of ATP-dependent membrane-associated transport proteins,
      ABCA3. Mutations in ABCA3 cause fatal respiratory disease in newborns and severe
      chronic lung disease in infancy. Expression of SP-B, -C, and ABCA3 are
      coregulated during late gestation by transcriptional programs influenced by
      thyroid transcription factor-1 and forkhead box a2, transcription factors that
      regulate both differentiation of the respiratory epithelium and transcription of
      genes required for perinatal adaptation to air breathing.

PMID- 15985751
TI  - Control of breathing and neonatal apnea.
AB  - Great strides have been made in our understanding of developmental respiratory
      neurobiology. A clear picture is, therefore, emerging of the physiological
      mechanisms that underlie apnea of prematurity. The ventral surface of the medulla
      and adjacent areas play a key integrative function for central CO2
      chemosensitivity and modulation of afferent inputs from peripheral chemoreceptors
      and laryngeal afferents. Maturational change in medullary neurotransmitter
      function appears to contribute to the physiological events that characterize
      apnea of prematurity. Despite this greater scientific insight, therapeutic
      strategies for neonatal apnea have changed little in 30 years. Xanthine therapy
      and continuous positive airway pressure remain the mainstay of therapy while
      other therapeutic approaches have been inadequately studied. Our understanding of
      a possible relationship between the triad of apnea, bradycardia and desaturation,
      and impaired neurodevelopmental outcome is also limited. These are all issues
      that need our attention if optimal therapy and outcome are to be provided for
      preterm infants with immature respiratory control.

PMID- 15985752
TI  - Surfactant metabolism in the neonate.
AB  - With the use of stable isotope-labeled intravenous precursors for surfactant
      phosphatidylcholine (PC) synthesis, it has been shown that the de novo synthesis
      rates in preterm infants with respiratory distress syndrome (RDS) are very low as
      are turnover rates. This is consistent with animal data. Surfactant therapy does
      not inhibit endogenous surfactant synthesis, and prenatal corticosteroids
      stimulate it. With the use of stable isotope-labeled PC given endotracheally,
      surfactant pool size was estimated. It turned out to be low in RDS, as expected.
      Similar studies were performed in term neonates with severe lung diseases. In
      general, patients with lung injury show a lower surfactant synthesis. The
      controversy around surfactant in congenital diaphragmatic hernia (CDH) persists:
      studies on CDH with and without extracorporeal membrane oxygenation yielded
      different results. In severe meconium aspiration syndrome surfactant synthesis
      was found to be decreased but surfactant pool size was maintained. It is possible
      and safe to study surfactant metabolism in human neonates with the use of stable
      isotopes. This can help in answering clinical questions and has the potential to
      bring new in vitro and animal findings about surfactant metabolism to the
      patient.

PMID- 15985753
TI  - History of surfactant up to 1980.
AB  - Remarkable insight into disturbed lung mechanics of preterm infants was gained in
      the 18th and 19th century by the founders of obstetrics and neonatology who not
      only observed respiratory failure but also designed devices to treat it.
      Surfactant research followed a splendid and largely logical growth curve.
      Pathological changes in the immature lung were characterized in Germany by
      Virchow in 1854 and by Hochheim in 1903. The Swiss physiologist von Neergard
      fully understood surfactant function in 1929, but his paper was ignored for 25
      years. The physical properties of surfactant were recognized in the early 1950s
      from research on warfare chemicals by Pattle in Britain and by Radford and
      Clements in the United States. The causal relationship of respiratory distress
      syndrome (RDS) and surfactant deficiency was established in the USA by Avery and
      Mead in 1959. The Australian obstetrician Liggins induced lung maturity with
      glucocorticoids in 1972, but his discovery was not fully believed for another 20
      years. A century of basic research was rewarded when Fujiwara introduced
      surfactant substitution in Japan in 1980 for treatment and prevention of RDS.

PMID- 15985754
TI  - History of surfactant from 1980.
AB  - The first successful trial of surfactant treatment for respiratory distress
      syndrome (RDS) was reported in 1980. Since then there have been numerous
      randomised trials demonstrating first, the efficacy of surfactant treatment in
      reducing pulmonary air leaks and increasing survival and second, assessing
      various other aspects of therapy. These studies show that multiple doses may be
      needed if surfactant is used to treat established RDS but early or prophylactic
      treatment is superior for infants with gestational ages less than 30 weeks.
      Natural surfactants (containing proteins) are more effective than synthetic
      products (protein free), the latter now being infrequently used. Natural
      surfactants vary and should not be considered to be equivalent in their effects.
      A porcine surfactant (poractant alfa) acts more rapidly than a bovine preparation
      (beractant) in infants with moderate to severe RDS. A meta-analysis of 5
      comparative studies suggests that a dose of 200 mg/kg of poractant alfa is
      associated with lower mortality compared with 100 mg/kg of beractant. Chronic
      lung disease remains a problem but it is hoped that early treatment with
      surfactant combined with extubation to continuous positive airway pressure will
      reduce this complication of prematurity. The newer synthetic surfactants,
      containing analogues of surfactant protein B or C, have undergone some trials for
      treatment of RDS but comparative studies which have just been published do not
      show that they are superior to existing natural surfactants. However, as they are
      more resistant to inactivation they may have a role in treatment of adult or
      acute RDS. The last 25 years have seen a large increase in basic science research
      on surfactants with determination of the structure and function of the four
      surfactant proteins probably being the most important advances. Future studies
      will focus on widening the indications for surfactant treatment, developing non
      invasive means of administration and assessing the role of the newer synthetic
      surfactants.

PMID- 15985755
TI  - Postnatal changes in pulmonary mechanics and energetics of infants with
      respiratory distress syndrome following surfactant treatment.
AB  - BACKGROUND: Postnatal alterations in pulmonary mechanics, energetics and
      functional residual capacity (FRC) describe the structural maturation of the
      preterm respiratory system. OBJECTIVE: To evaluate longitudinal changes in
      pulmonary function in infants with respiratory distress syndrome (RDS) treated
      with oxygen, positive pressure ventilation and synthetic surfactant (Exosurf).
      METHODS: Serial pulmonary function tests were performed in surfactant-treated
      infants [mean +/- SD birth weight (BW) = 1,112 +/- 276 g, gestational age (GA) =
      29 +/- 3 weeks] at postnatal ages: <3 days, 1, 2, 3, 4 and 6-8 weeks until term
      postmenstrual age (PMA). Tidal volume, pulmonary compliance (C(L)), pulmonary
      resistance (R(T)) and flow-resistive work were analyzed following simultaneous
      measurements of airflow and transpulmonary pressure signals. Serial FRC
      measurements were made in a randomly selected group. RESULTS: Prior to 28 weeks'
      PMA, C(L) was unchanged irrespective of GA. At age 1 week the likelihood ratio
      (LR) for bronchopulmonary dysplasia (BPD) based on C(L), R(T) and GA was
      predicted to be >90% for those with BW <750 g (LR >100) as compared to <10%
      probability (LR = 0.3) for infants >1,500 g. Significant linear increase in C(L)
      to PMA was evident >28 weeks' PMA (r = 0.86, p < 0.01) at 0.17 ml/cm H2O/kg/week.
      By term PMA, mean C(L) was 2.60 +/- 0.07 ml/cm H2O. Improvements in FRC of
      preterm infants with RDS who recovered occur at a more rapid rate ( approximately
      25 ml/kg) compared to those who developed BPD ( approximately 20 ml/kg).
      CONCLUSIONS: Slow but incremental postnatal pulmonary improvement, minimal <28
      weeks' PMA, were comparable for all infants. Along with diminished FRC, these
      changes reflect persistent deleterious effects of positive pressure ventilation,
      alveolar hyperoxia and unrecognized pulmonary overdistension.

PMID- 15985756
TI  - New synthetic surfactants--basic science.
AB  - The hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of surface
      active lipids to the air-liquid interface of the alveoli and are essential for
      alveolar stability and gas exchange. Synthetic surfactant preparations must
      contain at least one of these hydrophobic proteins, or analogs thereof, to have
      optimal effects when administered into the airways of patients with lung
      diseases. However, development of clinically active artificial surfactants has
      turned out to be more complicated than initially anticipated since the native
      hydrophobic proteins are structurally complex or unstable in pure form. The
      proteins have been replaced by different analogs which have the right
      conformation without forming oligomers. Increased understanding of the surfactant
      proteins will hopefully lead to development of effective synthetic surfactants
      which can be produced in large quantities for treatment of a wide range of
      respiratory disorders. Furthermore, the lipid composition seems to be important,
      as well as a high lipid concentration in the suspension. For successful treatment
      of many respiratory diseases, it is also desirable that the synthetic surfactant
      resists inactivation by plasma components leaking into the alveoli.

PMID- 15985757
TI  - New synthetic surfactants: the next generation?
AB  - Surfactant preparations have been proven to improve clinical outcome of infants
      at risk for or having respiratory distress syndrome (RDS). In clinical trials,
      ani mal-derived surfactant preparations reduce the risk of pneumothorax and
      mortality when compared to non-protein-containing synthetic surfactant
      preparations. In part, this is thought to be due to the presence of surfactant
      proteins in animal-derived surfactant preparations. Four native surfactant
      proteins have been identified. The hydrophobic surfactant proteins B (SP-B) and C
      (SP-C) are tightly bound to phospholipids. These proteins have important roles in
      maintaining the surface tension-lowering properties of pulmonary surfactant.
      Surfactant protein A (SP-A) and D (SP-D) are extremely hydrophilic and are not
      retained in the preparation of any commercial animal-derived surfactant products.
      These proteins are thought to have a role in recycling surfactant and improving
      host defense. There is concern that animal-derived products may have some batch
      to-batch variation regarding the levels of native pulmonary surfactant proteins.
      In addition, there is concern regarding the hypothetical risk of transmission of
      viral or unconventional infectious agents from an animal source. New surfactant
      preparations, composed of synthetic phospholipids and essential hydrophobic
      surfactant protein analogs, have been developed. These surfactant protein analogs
      have been produced by peptide synthesis and recombinant technology to provide a
      new class of synthetic surfactants that may be a suitable alternative to animal
      derived surfactants. Preliminary clinical studies have shown that treatment with
      these novel surfactant preparations can ameliorate RDS and improve clinical
      outcome. Clinicians will need to further understand any differences in clinical
      effects between available products.

PMID- 15985758
TI  - Ethical considerations in neonatal respiratory care.
AB  - Recent advances in neonatal care have greatly improved the chances for survival
      of very sick and/or very preterm neonates and have in fact changed the concept
      and the limits of viability. However, in some situations, when the infant's
      demise can only be postponed at the price of great suffering or when survival is
      associated with severe disabilities and an intolerable life for the patient and
      the parents, it may be unwise to employ the full armamentarium of modern neonatal
      intensive care. In those circumstances withholding or withdrawing mechanical
      ventilation and other life-saving, though invasive and painful, procedures might
      be a better option. This review examines the ethical principles underlying those
      difficult decisions, the most frequent circumstances where they should be
      considered, the role of parents and other parties in the decision-making process
      and the reported behavior of neonatologists in many American and European
      neonatal intensive care units.

PMID- 15985759
TI  - Influence of the cyto-protective agent amifostine on the pharmacokinetics of low
      dose Paclitaxel.
AB  - BACKGROUND: Pharmacokinetic parameters (PHK) of low-dose weekly paclitaxel (PAC)
      are not well known, particularly when administered with the cytoprotective agent
      amifostine (AMI). METHODS: Patients with non-small cell lung cancer (NSCLC)
      received PAC alone or PAC + AMI. Blood samples were drawn at the end of the
      infusion at 0, 0.25, 0.5, 1, 2 and 4 h for the measurement of plasma PAC using
      HPLC. Area under the concentration-time curve (AUC), the peak plasma
      concentrations (Cmax) and the residence time of paclitaxel in plasma at
      concentrations >0.1 microM (TPP >or=0.1) and >0.05 microM (TPP >or=0.05) were
      calculated using a two-compartmental model. ANOVA was used for statistical
      analysis. RESULTS: Pharmacokinetic studies were completed for 43 doses among 11
      patients receiving PAC alone and for 26 doses among 8 patients receiving the
      combination AMI + PAC (from the first to the fifth week). Statistically
      significant differences in all parameters except AUC were observed between the 2
      treatment groups. A significantly higher Cmax was observed for patients receiving
      PAC + AMI versus PAC alone. Both TPP >or=0.1 and TPP >or=0.05 were also more
      prolonged in AMI + PAC cycles. CONCLUSION: AMI produces a prolongation in PAC
      plasma circulation time. Further specifically designed studies are needed to
      quantify the resultant effects on PAC's efficacy and toxicity.

PMID- 15985760
TI  - Derivation of meropenem dosage in patients receiving continuous veno-venous
      hemofiltration based on pharmacodynamic target attainment.
AB  - BACKGROUND: Dosage recommendations for antibiotics in patients receiving
      continuous veno-venous hemofiltration (CVVH) should be based on pharmacodynamic
      requirements. For meropenem, this would be achieving appropriate time above the
      minimum inhibitory concentration (T > MIC). We employed Monte Carlo simulation to
      calculate the bactericidal target attainment for various dosing regimens of
      meropenem against Pseudomonas aeruginosa and Acinetobacter species. METHODS:
      Target attainment at 40% T > MIC was calculated for 5,000 simulated subjects
      receiving meropenem 1,000 mg every 12 and 8 h, and 500 mg every 12, 8 and 6 h.
      Pharmacokinetics were extrapolated from primary literature sources utilizing
      similar methods of CVVH. MIC data for P. aeruginosa and Acinetobacter species
      were derived from the US 2003 MYSTIC study. Target attainment at the breakpoint
      of 4 microg/ml was also calculated. RESULTS: Only regimens of 1,000 mg every 8 h
      and 500 mg every 6 h essentially achieve 100% target attainment at the
      breakpoint. However, due to higher peak concentrations, 1,000 mg every 8 h is
      able to attain improved target attainment against more resistant populations of
      P. aeruginosa and Acinetobacter species, thus providing the greatest probability
      of bactericidal exposure. CONCLUSION: Meropenem 1,000 mg every 8 h optimizes the
      pharmacodynamic profile in patients undergoing CVVH. Lower doses or increased
      dosing intervals should not be advocated for inpatients receiving this renal
      replacement technique. .

PMID- 15985761
TI  - TRAIL-induced apoptosis in human vascular endothelium is regulated by
      phosphatidylinositol 3-kinase/Akt through the short form of cellular FLIP and Bcl
      2.
AB  - BACKGROUND: Apoptosis of vascular endothelial cells plays a central role in
      angiogenesis and atherosclerosis. This study investigates the molecular
      mechanisms of endothelial apoptosis induced by tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) following inhibition of phosphatidylinositol 3
      kinase (PI3K). It examines downstream regulation and activation of the extrinsic
      and intrinsic pathways. METHODS AND RESULTS: By flow cytometry, TRAIL receptors 2
      and 3 were present to a greater extent than receptors 1 and 4. TRAIL reduced cell
      numbers in combination with the PI3K inhibitor LY 294002. TRAIL (100 ng/ml) with
      LY 294002 (20 micromol/l) activated the extrinsic pathway, causing progressive
      cleavage of caspase-8 and caspase-3. Activation of the intrinsic pathway
      proceeded by release of mitochondrial factors Smac/DIABLO and cytochrome c, and
      caspase-9 cleavage. LY 294002 reduced phosphorylated Akt (p-Akt), with early loss
      of the short form of cellular FLIP (c-FLIP(S)) and concurrent reduction of Bcl-2.
      Treatment with small interfering RNA against PI3K also reduced c-FLIP(S) and Bcl
      2, and cotreatment with TRAIL triggered caspase-3 cleavage. CONCLUSIONS: This
      study details the molecular regulation of TRAIL-induced apoptosis in vascular
      endothelium. Inhibition of PI3K reduces p-Akt, with concurrent reductions in c
      FLIP(S) and Bcl-2, and so renders endothelium sensitive to TRAIL-induced
      apoptosis through the extrinsic and intrinsic pathways.

PMID- 15985762
TI  - Altered postural control during the luteal phase in women with premenstrual
      symptoms.
AB  - The purpose of this study was to investigate postural control in women with and
      without premenstrual symptoms (PMS) in three hormonally verified phases of the
      menstrual cycle. Thirty-two women were recruited to participate in the study and
      25 of these women were included in the results. Menstrual cycle phases were
      determined by sex hormone analyses in serum and LH detection in urine. A
      prospective rating of PMS was used to divide the subjects into two groups: one
      with PMS (cyclic) and one without (non-cyclic). For measurement of postural
      control, subjects stood on a force platform (AMTI) in two-legged stance (eyes
      open and closed) and one-legged stance (eyes open and closed). There were no
      significant differences in the two-legged stance between the phases of the
      menstrual cycle or between groups. In one-legged stance with eyes open, there was
      a significant increase in postural displacement in the mid-luteal phase in the
      cyclic group, but no differences were detected between phases in the non-cyclic
      group. These findings may be related to the previously reported increased injury
      rate and psychomotor slowing in the luteal phase in women with PMS.

PMID- 15985763
TI  - Contrast-enhanced ultrasonography better identifies pancreatic tumor
      vascularization than helical CT.
AB  - BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is a recently introduced
      field of ultrasonography (US). To assess the ability of CEUS to identify the
      vascularization of solid pancreatic tumors in comparison to helical CT. METHODS:
      Forty-two resected pancreatic tumors, found at US, were studied with CEUS and
      helical CT. The tumor enhancement at CEUS was scored in comparison to the
      baseline aspect of the lesion and/or the extralesional pancreatic parenchyma
      together with the adjacent vessels during the dynamic study. All the lesions
      underwent pathological examination using H&E stains and CD34 markers with an
      evaluation of the microvessel density (MVD). The correlation of CEUS and helical
      CT with the MVD of the lesions was established with Spearman's test. RESULTS: The
      correlation of CEUS with the MVD of the lesions was significantly superior (Rs =
      0.914; p < 0.0001) to that of helical CT (Rs = 0.635; p < 0.0001). CONCLUSIONS:
      CEUS is better than helical CT in the identification of the vascularization of
      solid pancreatic tumors. CEUS, when the pancreatic gland is optimally visualized,
      should be therefore considered a complementary imaging modality in the
      characterization of pancreatic tumors. CEUS can be a valid onco-imaging modality
      for quantifying tumoral vascularization in a noninvasive and accurate way.

PMID- 15985764
TI  - Effects of the antioxidative vitamins A, C and E on liver metastasis and
      intrametastatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian
      hamsters.
AB  - BACKGROUND/AIMS: Antioxidative vitamins are known to inhibit metastasis.
      Therefore we evaluated the impact of vitamins A (retinol), C (ascorbic acid) and
      E (alpha-tocopherol) on liver metastasis in a model of ductal pancreatic
      adenocarcinoma in hamster. METHODS: One hundred and twenty male Syrian hamsters
      were randomized into 8 groups (Gr.) (n = 15). Gr. 1-4 were given 0.5 ml normal
      saline subcutaneously (s.c.) weekly, whereas Gr. 5-8 received 10 mg N
      nitrosobis(2-oxopropyl)amine (BOP)/kg body weight s.c. for 3 months for tumor
      induction. In the 13th week Gr. 2 and 6 were administered retinol, Gr. 3 and 7
      received ascorbic acid and Gr. 4 and 8 were given alpha-tocopherol orally. No
      treatment was performed in Gr. 1 and 5. After 24 weeks animals were sacrificed,
      pancreas and liver were histologically determined. Activities of glutathione
      peroxidase (GSH-Px), superoxide dismutase (SOD) and concentration of
      thiobarbituric-acid-reactive substances (TBARS) were analyzed in hepatic tissue.
      RESULTS: Retinol and alpha-tocopherol decreased the incidence of liver metastases
      (44.4 vs. 86.7%, p < 0.05). The number and size of liver metastases were
      significantly reduced by retinol. Activities of GSH-Px and SOD were increased and
      concentration of TBARS was decreased in NML and LiMe by all vitamins. CONCLUSION:
      Obviously, antioxidative vitamins prevent oxidative stress in hepatocytes. This
      may be one mechanism decreasing liver metastasis in pancreatic cancer in the
      present trial.

PMID- 15985765
TI  - Pancreatic hepatocellular tumor.
AB  - BACKGROUND: Hepatocellular differentiation of pancreatic cells has been observed
      under certain conditions in several species, including humans. Their cell of
      origin and biology has remained controversial. Generally, these lesions have been
      considered a degenerative process. The present study describes a neoplastic
      hepatocellular lesion in Syrian hamsters. METHODS AND RESULTS: Syrian hamsters
      were treated with a high dose of pancreatic carcinogen, N-nitrosobis(2
      oxopropyl)amine. The lesion was confined within a single islet and expressed
      albumin and HSA (hepatocyte-specific antigen). The pleomorphic tumor cells
      exhibited numerous mitotic figures and were intermingled with insulin and
      glucagon cells. The hamster had multicentric premalignant and malignant ductal
      type lesions, most of which appeared to arise from within the islets. This is the
      first demonstration of pancreatic hepatoma. CONCLUSION: Pancreatic islet cells
      appear to have the potential to transdifferentiate into neoplastic hepatocytes.

PMID- 15985766
TI  - Pancreatic juice cytology in IPMN of the pancreas.
AB  - BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a
      disease ranging from adenoma to borderline (with moderate dysplasia) and further
      to carcinoma (noninvasive and invasive) and surgical strategy is different by the
      grades of dysplasia. METHODS: Preoperative pancreatic juice cytology in IPMN was
      reviewed in 71 patients with IPMN who underwent surgical resection. RESULTS: The
      IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10.
      The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In
      4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was
      class IV or V. One of the 4 cases was considered to be an overdiagnosis of
      cytology, but the other 3 cases were considered to be a consequence of
      accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal
      adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice
      cytology was higher in IPMN of the main duct type with mucin hypersecretion and
      with mural nodules. CONCLUSIONS: These findings suggest that pancreatic juice
      cytology in IPMN is useful especially in the main duct type with mucin
      hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology
      is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic
      carcinoma should be suspected.

PMID- 15985767
TI  - Pancreatic volume associated with endocrine and exocrine function of the pancreas
      among Japanese alcoholics.
AB  - BACKGROUND/AIMS: The pancreas is often damaged by excessive alcohol consumption.
      Because alcohol-related problems and diabetes mellitus (DM) are increasing in
      Japan, this cross-sectional study was designed to investigate how pancreatic
      volume (PV, calculated using multi-slice helical computed tomography) represents
      alcohol consumption and both endocrine and exocrine pancreatic function among
      alcoholics. METHODS: Consenting male and female inpatients undergoing psychiatric
      therapy for alcoholism from June 2003 to May 2004 were subjected to four-slice
      MCT to determine PV. Fasting plasma glucose (FPG) and serum lipase levels were
      examined for endocrine and exocrine pancreatic functions, respectively. RESULTS:
      The average PVs of 535 male and 117 female patients (57.2 +/- 21.91 ml and 54.5
      +/- 17.56 ml, respectively) were related to age and height (H) but not to body
      weight (W). Lipase values had a strong relationship with PV/W. Multiple
      regression analysis revealed weak associations between PV and both daily ethanol
      consumption and duration of habitual drinking. The diagnosis of DM in 109 of
      these alcoholics was more strongly associated with the PV/W value than with PV or
      PV/H. CONCLUSION: The association of PV with endocrine and exocrine functions
      suggests new markers, especially PV/W, for the assessment of DM among alcoholic
      patients.

PMID- 15985768
TI  - Fecal elastase 1, serum amylase and lipase levels in children with cholestasis.
AB  - BACKGROUND/AIM: The pancreatic functions of children with cholestatic liver
      diseases were unclear. Due to anatomic vicinity and common ontogenic origin,
      hepatobiliary disorders of infancy may also affect pancreatic function. The aim
      of the study was to evaluate the exocrine pancreatic function and common
      pancreatic function tests in children with cholestatic disorders. METHODS: In 40
      children with cholestasis, fecal elastase 1 (FE1) concentrations were measured.
      Serum amylase and lipase values were tested. The diagnoses included 32 patients
      with extrahepatic cholestasis (biliary atresia (BA) and choledochal cyst), and 8
      patients with intrahepatic cholestasis (progressive familial intrahepatic
      cholestasis and Alagille syndrome). None had renal insufficiency or clinical
      symptoms/signs of acute pancreatitis. RESULTS: All the patients had normal FE1
      (>200 microg/g). Nineteen percent (7/37) had elevated serum amylase levels (>100
      U/l). Thirty-two percent (12/37) had elevated serum lipase levels above the
      normal (>120 U/l). Seventy-three percent (8/11) of BA patients with bilirubin >2
      mg/dl had elevated serum lipase levels compared to 18% (3/17) with bilirubin < or
      = 2 mg/dl (p = 0.0036). None had detectable pancreatic abnormality on
      ultrasonography and magnetic resonance images. CONCLUSIONS: None of the
      cholestatic children in this study had exocrine pancreatic insufficiency as
      detected by FE1. Hyperamylasemia and/or hyperlipasemia were frequently found. In
      children with BA, those with impaired biliary excretion tended to have elevated
      serum pancreatic enzymes as compared with those who had no jaundice. A decreased
      hepatic metabolism may be the cause.

PMID- 15985769
TI  - Intraoperative radiotherapy for patients with carcinoma of the pancreas.
AB  - BACKGROUND/AIMS: Local recurrence is one of the most common sites of failure
      after resection of exocrine pancreatic adenocarcinoma. Intraoperative
      radiotherapy (IORT) involves delivery of high doses of irradiation to the
      pancreas in patients with locally advanced disease, and to the surgical bed
      following pancreatic resection while uninvolved and dose-limiting tissues are
      displaced. Here we report our current experience with IORT in patients with
      pancreatic cancer. METHODS: IORT was given as adjuvant treatment in 18 and
      palliatively in 37 patients. External beam radiotherapy (EBRT) was in addition
      delivered to 10 patients in the resection group and 29 in the palliation group.
      The cancer diagnosis was verified histologically and/or cytologically in all
      patients. RESULTS: There was no hospital mortality. Among the resected patients
      the postoperative complication rate was 44% (8/18). The corresponding figure
      after palliative operation was 14% (5/37). None of the postoperative
      complications were regarded as a consequence of IORT. Symptoms and complaints
      were observed after EBRT in 70 and 90%, respectively, in the two groups. However,
      no symptom was serious in nature. After resection the median survival time was 9
      months (range 3-58) and local recurrence was diagnosed in 33% (6/18). In the
      palliatively treated patients the median survival was 7 months (range 2-30) and
      pain requiring opioids was present in 89% (24/27) of the patients within 6
      months. CONCLUSION: In this nonrandomized study no apparent beneficial effects
      were seen after IORT in patients with pancreatic cancer, neither adjuvantly nor
      palliatively. However, radiotherapy did not lead to any major complications.

PMID- 15985770
TI  - Patch clamped single pancreatic zymogen granules: direct measurements of ion
      channel activities at the granule membrane.
AB  - BACKGROUND/AIM: Pancreatic acinar cells are involved in the secretion of
      digestive enzymes. Digestive enzymes in pancreatic acinar cells are stored in
      membrane-bound secretory vesicles called zymogen granules (ZGs). The swelling of
      ZGs is implicated in the regulation of the expulsion of intravesicular contents
      during secretion. The molecular mechanism of ZG swelling has been previously
      elucidated. It has been further demonstrated that the water channel aquaporin-1,
      the potassium channel IRK-8, and the chloride channel CLC-2, are present in the
      ZG membrane and involved in ZG swelling. However, a direct measurement of these
      ion channels at the ZG membrane in intact ZGs had not been performed. The aim of
      this study was to investigate the electrical activity of single ZGs and verify
      the types of channels found within their membrane. METHODS: ZGs from pancreatic
      acinar cells were isolated from the pancreas of Sprague-Dawley rats. Direct
      measurements of whole vesicle currents, in the presence and absence of ion
      channel blockers (quinine, glyburide and DIDS), were recorded following
      successful patching of single ZGs. CONCLUSION: In this study, we were able, for
      the first time, to patch single ZGs and study ion channels in their membrane. We
      were able to record currents across the ZG membrane and, utilizing ion channel
      blockers, confirm the presence of the chloride channels CLC-2 and the potassium
      channel IRK-8 (Kir6.1), and additionally demonstrate the presence of a second
      chloride channel CLC-3.

PMID- 15985771
TI  - Diagnostic criteria in predicting a biliary origin of acute pancreatitis in the
      era of endoscopic ultrasound: multicentre prospective evaluation of 213 patients.
AB  - BACKGROUND: No study on bioclinical criteria predicting a biliary origin for
      acute pancreatitis has included endosonography as a reference examination. Re
      examination of bioclinical parameters deserves consideration in the era where
      other causes are known (e.g. hereditary, autoimmune). AIM AND METHODS: To
      determine the performance of bioclinical markers in predicting a biliary origin
      of acute pancreatitis where the diagnosis of biliary lithiasis was established or
      ruled out using endosonography. Only patients with a first acute episode of
      pancreatitis were included. RESULTS: 213 patients (male: 55%; median age: 56
      years) were prospectively included in 14 centres. Causes of acute pancreatitis
      were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset
      and admission was <48 h in 80%. Endosonography was the sole method establishing
      the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis,
      age, female sex, declared alcohol consumption, elevated aspartate and alanine
      transaminases on admission, gammaglutamyl transferase, alkaline phosphatase,
      total bilirubin, lipase, mean corpuscular volume were predictive of a biliary
      origin. Only age (p < 0.0001), sex (p < 0.0008) and alanine transaminase (p <
      0.0004) remained significant at multivariate analysis. At age 50, the respective
      sensitivity and specificity were 73 and 65%. With an elevated alanine
      transaminase at 2 times the upper limit of normal range, the respective
      sensitivity and specificity were 74 and 84%. The probability of a biliary origin
      of acute pancreatitis could be estimated by the following formula: = 1/1 +
      exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase).
      CONCLUSION: When endosonography is performed to confirm or exclude a biliary
      origin of acute pancreatitis, age, sex and alanine transaminase at admission are
      the only factors predictive of a biliary cause.

PMID- 15985772
TI  - Clinical considerations of primary hydatid disease of the pancreas.
AB  - BACKGROUND: The pancreas is a rare primary location of hydatid disease. The
      purpose of our study is to gain more insight into this entity and to focus on the
      management and the diagnostic approach to the disease. METHODS: The medical
      records of 5 patients with hydatid cysts of the pancreas were reviewed. RESULTS:
      Four of the cysts were primary, while in 1 case a coexisting cyst was found in
      the liver. The body and tail of the pancreas were the most common locations.
      Clinical presentation varied according to the anatomic location of the cyst.
      Abdominal pain, discomfort and vomiting were the main clinical symptoms. One
      patient presented with obstructive jaundice, while another patient manifested a
      mild episode of anaphylactic shock. The indirect hemagglutination test was
      positive in 3 of 4 cases. A computed tomography scan successfully imaged all
      cysts and calcification of the cystic wall was found in 3 of 4 cases. All
      patients underwent surgical therapy. Hydatid cysts in the tail of the pancreas
      were successfully treated with distal pancreatectomy, while cysts in the body and
      head of pancreas were treated with proper evacuation, pericystectomy and
      omentoplasty. The postoperative course was uneventful in all patients except 1
      who presented a pancreatic fistula and was re-operated. The mean length of
      hospitalization after surgery was 11-12 (range 10-13) days, except for the
      patient who needed to be re-operated. No evidence of cyst recurrence was observed
      during the follow-up period. CONCLUSIONS: Hydatid cystic masses of the upper
      abdomen might also originate from the pancreas especially in endemic countries.
      Surgical excision of the entire cystic lesion remains the optimal treatment,
      offering hope for a complete cure.

PMID- 15985773
TI  - A resected case of multiple intraductal papillary mucinous tumors of the pancreas
      with US-guided ductal branch-oriented partial pancreatectomy.
AB  - A 69-year-old man with epigastralgia was admitted on August 26, 2002 and
      diagnosed with multiple intraductal papillary mucinous tumors by various
      imagings. The cystic tumor of pancreas head had a diameter of 2 cm, and the mural
      nodule of the cystic tumor measured only 3 mm. In the pancreas body the cystic
      tumor was measured at 1.5 cm with the mural nodule of the cystic tumor measuring
      3 mm. It was believed that the tumors were benign. However, a mural nodule of the
      cystic lesion was recognized, thus, the possibility of malignancy could not be
      completely ruled out. The reduction operation for preservation of pancreatic
      parenchyma should be selected for these circumstances. Ductal branch-oriented
      partial pancreatectomy was performed on September 6, 2002 with intraoperative
      ultrasonography and a Cavitron Ultrasonic Aspirator, preserving the main
      pancreatic duct and normal pancreatic parenchyma. The operation was successful,
      and the histopathological diagnosis of the tumors was intraductal papillary
      adenoma of the pancreas.

PMID- 15985774
TI  - Primary sclerosing cholangitis associated with limy bile and acute pancreatitis.
AB  - Primary sclerosing cholangitis (PSC) as the cause of acute pancreatitis (AP) is a
      rare phenomenon. Here, we report the first case of PSC associated with limy bile
      (LB) as well as AP. In this case, spontaneous outflow of the LB occurred, and the
      AP resolved on its own with conservative management. In addition to the
      administration of ursodeoxycholic acid, endoscopic intervention was undertaken
      and the patient remains symptom free to date. This report describes a unique case
      in which PSC, LB, and AP occurred in the same patient. The association of these
      rare conditions is also discussed.

PMID- 15985775
TI  - The isolated perfused liver response to a 'second hit' of portal endotoxin during
      severe acute pancreatitis.
AB  - BACKGROUND/AIM: During severe acute pancreatitis (AP), the liver may show an
      exaggerated response to the inflammatory products of gut injury transported in
      the portal vein. Our aim was to explore liver proinflammatory mediator production
      after a 'second hit' of portal lipopolysaccharide (LPS) during AP. METHODS:
      Twenty-four rats underwent one of three 'first-hit' scenarios: (1) severe AP
      induced by intraductal glycodeoxycholic acid injection and intravenous caerulein
      infusion, (2) sham laparotomy, or (3) no first intervention. Eighteen hours
      later, all animals received a 'second hit' of portal LPS in an isolated liver
      perfusion system. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)
      1beta, and IL-6 concentrations were measured in portal and systemic serum, and in
      the perfusate 30 and 90 min after the 'second hit'. Neutrophil activation by the
      perfusate was assayed using dihydrorhodamine-123 fluorescence. RESULTS: We
      observed a six-fold increase in IL-6 concentration across the liver during AP.
      All livers produced TNF-alpha after the portal LPS challenge, but this was not
      exaggerated by AP. No differential neutrophil activation by the perfusate was
      seen. CONCLUSION: TNF-alpha, IL-1beta, IL-6 and neutrophil activator production
      by the isolated perfused liver, in response to a 'second hit' of portal LPS, does
      not appear to be enhanced during AP.

PMID- 15985776
TI  - [Status of alternative medicine in Crohn disease and ulcerative colitis patents:
      a questionnaire survey].
AB  - BACKGROUND: Patients with M. Crohn or colitis ulcerosa live with a chronic
      disease. Pharmaceuticals used in convention-al medicine have been proven to be
      effective but can have strong side-effects. Thus, it is no surprise that affected
      patients are very interested in complementary and alternative medicine (CAM).
      OBJECTIVE: The aim of our survey was to investigate the use and the application
      of CAM by patients with M. Crohn and colitis ulcerosa in Switzerland. PATIENTS
      AND METHODS: Out-patients of the gastroenterological centre at the University
      Hospital Bern and of two gastroenterological private practices in a medium-sized
      city completed a self-administered questionnaire on CAM. Demographic variables,
      disease-related data, use of different approaches of complementary medicine,
      attitudes towards and the use of CAM were asked for. RESULTS: Out of 204 mailed
      questionnaires 71% (144) could be evaluated, 44% from patients of the University
      Hospital, 56% from patients of the gastroenterological private practices. CAM was
      used by 47% of the patients. The most commonly used methods of CAM were:
      homeopathy, traditional Chinese medicine and acupuncture. 67% of the patients
      benefitted by CAM in the long run, whereas 10.5% suffered a relapse of their
      disease during CAM therapies. The main reason for the patients to apply to CAM
      was to complement conventional treatment. CONCLUSION: Our survey points out that
      the studied out-patients have a strong interest in CAM. It is therefore important
      that clinical research in the various unconventional therapies will be further
      promoted.

PMID- 15985777
TI  - Integration of complementary and alternative medicine into German medical school
      curricula -- contradictions between the opinions of decision makers and the
      status quo.
AB  - INTRODUCTION: There is a growing demand for complementary and alternative
      medicine (CAM) in Western societies. This trend has lead to the gradual
      integration of CAM courses into medical school curricula. The aim of this study
      was to survey key decision makers at German medical schools with regard to their
      views on CAM and to examine the extent to which CAM has already been integrated
      in the German medical school system. MATERIALS AND METHODS: A questionnaire was
      sent to 753 clinic and institute directors at German medical schools. RESULTS: A
      total of 500 questionnaires (66%) were returned. 39% of respondents had a
      positive opinion of CAM, 27% had a neutral opinion and 31% had a negative
      opinion. 3% of respondents were unsure. The CAM therapies viewed most positively
      were osteopathy (52%), acupuncture (48%), and naturopathy (41%). Most respondents
      were in favor of integrating CAM into the medical system. However, a larger
      percentage favored its use in research (61%) and teaching (59%) rather than in
      the treatment of patients (58%). Only 191 respondents (38%) indicated that CAM
      treatment methods had been integrated into the curriculum of their respective
      medical schools. In these schools, CAM was mainly used in patient treatment
      (35%), followed by research (22%) and education (21%). CONCLUSIONS: Our data show
      that the majority of respondents were in favor of integrating CAM into medical
      school curricula. However, at the time of our survey, only a small percentage of
      medical schools had actually put this into practice. The reasons for this
      discrepancy are unclear and should be further investigated.

PMID- 15985778
TI  - [Oral enzyme therapy for chronic hepatitis C--a retrospective analysis].
AB  - BACKGROUND AND OBJECTIVE: Data from a randomized trial in hepatitis C infected
      Egyptian patients suggest that the oral intake of the enzyme preparation
      Phlogenzym results in a significant reduction of aminotransferase levels and is
      equally effective to the therapy with interferon alpha. In our study, we
      investigated whether comparable effects can be found in daily practice in German
      patients. PATIENTS AND METHODS: We retrospectively evaluated the aminotransferase
      levels of all patients with chronic hepatitis C who were treated with Phlogenzym
      at a dose of 6 tablets/day in our outpatient department between 1998 and 2003.
      Inclusion criteria for the study were treatment duration >3 weeks and elevated
      alanine-aminotransferase (ALT)levels 6 months prior to and at the beginning of
      the treatment with Phlogenzym. Liver cirrhosis Child B or C, interferon therapy
      within the last 3 months before treatment with Phlogenzym and alcohol intake >30
      g/day were exclusion criteria. RESULTS: 22 patients were included into the
      analyses. The mean duration of treatment with Phlogenzym was 77 +/- 41 days. ALT,
      aspartate-aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) levels
      did not change significantly during treatment. Fitting a generalized linear
      model, we estimated that a hypothetical patient who started with a baseline value
      of 50 U/I after 90 days of treatment ends up in an ALT level of 52 U/I (95%-CI:27
      77 U/I), an AST level of 51 U/I (35-67 U/I) and a GGT level of 42 U/I (22-61
      U/I). 5 out of 22 patients had to stop treatment because of side effects.
      CONCLUSION: 6 tablets Phlogenzym per day do not seem to reduce permanently
      elevated aminotransferases in patients with chronic hepatitis C.

PMID- 15985779
TI  - [Does dark field microscopy according to Enderlein allow for cancer diagnosis? A
      prospective study].
AB  - BACKGROUND: Dark field microscopy according to Enderlin claims to be able to
      detect forthcoming or beginning cancer at an early stage through minute
      abnormalities in the blood. In Germany and the USA, this method is used by an
      increasing number of physicians and health practitioners (non-medically qualified
      complementary practitioners), because this easy test seems to give important
      information about patients' health status. OBJECTIVE: Can dark field microscopy
      reliably detect cancer? MATERIALS AND METHODS: In the course of a prospective
      study on iridology, blood samples were drawn for dark field microscopy in 110
      patients. A health practitioner with several years of training in the field
      carried out the examination without prior information about the patients.
      RESULTS: Out of 12 patients with present tumor metastasis as confirmed by
      radiological methods (CT, MRI or ultra-sound) 3 were correctly identified.
      Analysis of sensitivity (0.25), specificity (0.64), positive (0.09) and negative
      (0.85) predictive values revealed unsatisfactory results. CONCLUSION: Dark field
      micoroscopy does not seem to reliably detect the presence of cancer. Clinical use
      of the method can therefore not be recommended until future studies are
      conducted.

PMID- 15985780
TI  - Assessing homeopathic proving using questionnaire methodology: consideration and
      implications for future studies.
AB  - Homeopathic pathogenetic trials (or provings) provide the foundations for the
      clinical practice of homeopathy. The most recent review of proving studies
      indicated that provings are generally of poor methodological quality. Methods to
      improve the quality and scientific rigour are needed to critically assess the
      clinical basis of homeopathy. This article describes a methodology using a
      symptom diary with a selection of predefined remedy specific symptoms (proving
      questionnaire). The proving questionnaire was developed as an alternative to the
      traditional qualitative proving methods in an attempt to provide a quantitative
      method that could rigorously validate the original provings. This article
      considers the advantages and disadvantages of this approach and provides
      suggestions for future work in this area.

PMID- 15985781
TI  - Building an evidence house: challenges and solutions to research in complementary
      and alternative medicine.
AB  - Conventional biomedicine is having a revolution in scientific input from genomics
      to imaging to information and systems biology. Biomedicine is also struggling to
      find a balance between rigor and relevance such that public values and health
      care costs can be properly managed. At the same time complementary and
      alternative medicine (CAM) is becoming increasingly popular. Can rigorous
      research in CAM be developed? Can it be held to the same standards of evidence as
      conventional medicine? Should it be held to those standards? Are there additional
      standards and better integration strategies for CAM that are of value to all
      medicine, complementary or conventional? In this article, I address some of the
      major challenges faced by investigators when conducting research in CAM. These
      challenges include: quality standards of research; the evolving nature of
      science; accommodating pluralism; addressing underlying assumptions; and,
      managing controversial topics in CAM research. These challenges are formidable
      and will require that CAM attain a sufficient level of science to move it out of
      the margins of health care and a more careful approach to research integration
      that can keep its focus on public benefit and the public's health. I suggest a
      framework of an 'Evidence House' for addressing many of these challenges.

PMID- 15985782
TI  - Northeastern Society of Plastic Surgeons keynote lecture.

PMID- 15985783
TI  - A simple guide to inframammary-fold reconstruction.
AB  - In breast reconstruction, the inframammary fold (IMF) is one of the most
      difficult anatomic structures to faithfully recreate. Nonetheless, it is critical
      to achieving optimal aesthetic outcome. We describe our technique for
      reconstructing the IMF as a secondary procedure after breast reconstruction using
      a Steinman pin template based on the curvature of the normal contralateral IMF.
      Twelve cases of IMF reconstruction using this technique have been performed with
      good aesthetic outcome and high reliability, with the longest follow-up being
      over 10 years. Advantages include (1) use of the Steinman pin template based on
      the contralateral side maximizes attainable symmetry, (2) an additional incision
      is not required, (3) precise suture placement is facilitated by visualization of
      the pin inside the breast cavity, and (4) use of a running internal mattress
      suture avoids a scalloped appearance, and smooth curvature of the IMF over its
      entire width is easily and reliably obtained. This technique is applicable to
      postoperative deformities from breast reconstruction using flaps, implants, or
      both.

PMID- 15985784
TI  - Nipple-areola reconstruction following chest-wall irradiation for breast cancer:
      is it safe?
AB  - Radiation therapy (RT) is considered by some to be a contraindication to nipple
      areola reconstruction (NAR) particularly in patients with breast implant
      reconstruction. In this retrospective chart review, all patients who underwent
      breast reconstruction with tissue expanders and implants from 1997-2003 were
      reviewed. A subset of patients with a history of radiation therapy (pre- or
      postoperative) was identified. Postoperative complications, surgical technique,
      and the time course of reconstructive procedures were analyzed. Thirteen percent
      of patients with a history of RT had NAR compared with 36% of similarly
      reconstructed patients without a history of RT. Reconstruction was accomplished
      using a variety of local flaps, with an overall complication rate of 25%. Nipple
      areola reconstruction after chest-wall irradiation in patients reconstructed with
      breast implants should be performed in carefully selected patients. Acceptable
      surgical candidates demonstrate resolution of acute radiation changes, no
      evidence of late radiation changes, and appropriate thickness of the mastectomy
      skin flaps.

PMID- 15985785
TI  - Complications in smokers after postmastectomy tissue expander/implant breast
      reconstruction.
AB  - Smoking is universally considered to be a risk factor for surgical complications.
      The incidence of complications following tissue expander/implant breast
      reconstruction in patients who smoke has not been previously evaluated.A review
      of complications following tissue expander/implant reconstruction in 515 patients
      was performed. Patients who had 2-stage, tissue expander/implant reconstruction
      at Memorial Sloan-Kettering Cancer Center between May 2002 and December 2003 were
      included. Complications in smokers (n=132) and nonsmokers (n=383) were compared.
      The rate of overall complications, reconstructive failure, mastectomy flap
      necrosis, and infectious complications was significantly higher in smokers
      compared with nonsmokers. The rate of complications in ex-smokers was also higher
      than in nonsmokers. Using multivariate statistical analysis to adjust for
      confounding variables, smoking was identified as independent predictor of
      postoperative complications.A significant association between smoking status and
      postoperative complications exists. Thus, smokers who undergo postmastectomy
      expander/implant reconstruction should be informed of the increased risk of
      surgical complications and should be counseled on smoking cessation.

PMID- 15985786
TI  - Avoiding free nipple grafts during reduction mammaplasty in patients with
      gigantomastia.
AB  - Excessive breast hypertrophy or gigantomastia (>2000 g excision of tissue per
      breast) has traditionally been approached with breast amputation and free nipple
      grafting during reduction mammaplasty procedures. Disadvantages of free nipple
      grafts include loss of sensation, poor projection, uneven nipple-areolar complex
      pigmentation, and loss of lactation. We report our experiences utilizing the
      inferior pedicle technique of reduction mammaplasty with successful preservation
      of the nipple-areola complex for patients with gigantomastia. Between 2001 and
      2003, 15 patients (ages 19--45) were identified with gigantomastia through review
      of pathology and operative reports. The inferior pedicle technique was performed
      in all cases by the attending staff assisted by plastic surgery residents.
      Patients were followed regularly from 1 week up to 1 year postoperatively. All
      patients reported relief from the physical sequelae of breast hypertrophy. One
      patient experienced bilateral partial nipple desquamation; she maintained
      sensation throughout and healed well with moist dressings. Otherwise, there were
      no complications and all patients achieved satisfactory esthetic outcomes. Our
      results suggest that inferior pedicle technique can be successfully performed in
      patients with gigantomastia. Breast amputation with free nipple grafting need not
      be considered standard practice for this patient population. Maintaining a wider
      pedicle base and meticulous intraoperative handling of the pedicle may contribute
      to the increased viability of the nipple-areolar complex during these cases.

PMID- 15985787
TI  - The use of calcium hydroxylapatite for nipple projection after failed nipple
      areolar reconstruction: early results.
AB  - Numerous studies have shown that the final stage in breast reconstruction,
      creation of the nipple-areolar complex, correlates highly with patient
      satisfaction and acceptance of body image. There are many different techniques,
      including nipple sharing, free-composite grafts, and local "pull-out" flaps, all
      of which are vulnerable to an unpredictable degree of loss of projection and
      possible need for reoperation. This leads to problems with symmetry and
      overbuilding the initial reconstruction with wider-based, larger flaps, which may
      cause breast-contour changes. We have used calcium hydroxylapatite (Radiesse,
      Bioform Inc., Franksville, WI) following nipple-areolar reconstruction to
      maintain or restore projection in selected breast-reconstruction patients.
      Approximately 0.4-1 mL of calcium hydroxylapatite was injected subdermally using
      a 27-gauge needle in 6 selected patients. All patients tolerated the office
      procedure well without the need for local anesthesia. We report initial short
      term success, with 100% patient satisfaction, minimal loss of projection, and no
      complications. Semipermanent injectable soft-tissue fillers such as calcium
      hydroxylapatite may be useful in selected patients as a simple solution to the
      difficult problem of the lack of nipple projection following reconstruction.

PMID- 15985788
TI  - Reliable soft tissue augmentation: a clinical comparison of injectable soft
      tissue fillers for facial-volume augmentation.
AB  - While injectable fillers for facial-volume augmentation have been extensively
      marketed, there are few published reports comparing the clinical efficacy and
      cost-effectiveness of multiple injectable agents for soft-tissue augmentation in
      the face. We present our experience in 976 patients with the use of 4 common
      injectable agents: autologous fat, Hylaform, Restylane, and Radiesse. We analyzed
      the injection characteristics of each filler, including injection volume,
      complication rate, revision rate, and longevity, across 3 commonly treated
      anatomic regions: the nasolabial fold, glabella, and lips. We subsequently
      performed a detailed cost-effectiveness analysis of each filler in each anatomic
      region. Our results demonstrate that autologous fat transplantation is ideally
      suited for the treatment of the nasolabial fold and glabella, particularly in
      combination with other procedures. Fat grafting to the lips is limited to use as
      an adjunct to other facial surgery due to the prolonged recovery time required.
      We prefer Radiesse for the isolated treatment of the nasolabial folds and
      glabella. However, Radiesse is not recommended in the lips due to the increased
      incidence of complications. Last, the hyaluronic fillers Restylane and Hylaform
      have an excellent safety profile and are our first choice for isolated lip
      augmentation procedures.

PMID- 15985789
TI  - Multilayer reconstruction of abdominal wall defects with acellular dermal
      allograft (AlloDerm) and component separation.
AB  - Multiple techniques have been employed for the repair of abdominal incisional
      hernias with varying rates of success. Primary fascial apposition and prosthetic
      implantation have been associated with high rates of secondary recurrence,
      infection, and other complications, often due to insufficient alleviation of
      tension and implant intolerance. This study evaluates the repair of incisional
      and recurrent abdominal hernias with multilayered acellular dermal allograft
      (AlloDerm; LifeCell Corporation, Branchburg, NJ) and musculofascial separation.
      Patients with incisional or recurrent abdominal hernias were treated between
      January 2003 and March 2004. The surgical technique involved musculofascial
      release of the external oblique, followed by a double-layer implantation of
      dermal allograft. The primary allograft layer was placed as an "underlay"
      interposition, sutured under moderate tension beneath the fascial edges of the
      defect. When minimal tension remained, the native fascial margins of the defect
      were directly repaired. A second allograft layer was then placed and sutured to
      the superficial aspect of the ventral fascia to complete the repair. Data were
      reviewed retrospectively. Sixteen patients were treated. There were 10 males and
      6 females, mean age 56 years (range 44--72 years). Fifteen patients (94%) had
      previous hernia repair procedures, and 6 patients (38%) had undergone 2 or more
      previous procedures. Nine patients (56%) were treated with hernia site infections
      or prosthetic exposure. Mean follow-up is 16 months (range 9 to 23 months). There
      were 2 seromas (13%). One patient (6%) developed a wound dehiscence with
      allograft exposure that healed by secondary intention. There were no recurrences.
      By minimizing tension and providing a durable biocompatible matrix for support,
      component separation with bilaminar acellular dermal allograft should be
      considered for the repair of complex and recurrent ventral hernias.

PMID- 15985790
TI  - Alloplastic reconstruction of large cranio-orbital defects: a comparative
      evaluation.
AB  - Norian CRS, Bone Cement (Synthes CMF), and Mimix (Lorenz) have been used to
      reconstruct large cranio-orbital defects in 85 patients. Resorbable mesh
      (Macropore), used in combination in selected patients, obviates dura pulsations
      that have been postulated to cause fragmentation of alloplastic material. Norian
      is composed of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate,
      and calcium carbonate. Admixture with NaPO4 creates dahllite, which has a higher
      carbonate content (4%--6%) than hydroxyapatite (0%). CRS is soluble at low pH,
      facilitating its resorption and replacement by bone. In contradistinction, Mimix
      is converted to aqueous solution at 37 degrees C, supports fibrovascular ingrowth
      and bony interdigitation at the implant-material surface. Forty-five adults (mean
      age=42 years) and 40 children (mean age=8 years) were evaluated with respect to
      etiology of defect, size, location, gram usage of alloplast material, type of
      alloplast, postoperative clinical course, and complications. A minimum of 3-year
      follow-up is available; 22 adult patients additionally underwent resorbable mesh
      reconstruction. There were 7 (8%) complications, including infection, extrusion,
      a sterile loculated fluid collection and fragmentation. No difference in
      complication rate was noted between biomaterials. Two additional patients
      exhibited resorption (Norian), necessitating reaugmentation. Alloplastic
      replacement of cranio-orbital defects has recently advanced dramatically.
      Bivalved cranial bone grafting with its attached morbidity and sequelae can be
      avoided. Resorbable mesh allows for the placement of alloplast material in larger
      defects while avoiding dura pulsation causing alloplast fragmentation. In
      avoiding titanium type reconstruction, it obviates any interference with
      radiologic diagnosis and radiotherapeutic modalities. Long-term results are
      needed to assess bone growth within alloplast and to study bone growth in
      alloplastic reconstructed pediatric patients.

PMID- 15985791
TI  - Sonographically guided percutaneous carpal tunnel release: an anatomic and
      cadaveric study.
AB  - Minimally invasive techniques have become the standard of care for multiple
      procedures. This paper demonstrates both the surgeons' capacity to perform an
      accurate anatomic evaluation of the hand and forearm (n=10) and the use of this
      anatomic information to accurately perform sonographically guided, percutaneous
      carpal tunnel release using a single-portal endoscope without direct or indirect
      visualization in a cadaver model (n=6). Open dissection was then performed to
      confirm complete ligament transection and to evaluate the surrounding structures
      for injury. In all 6 cadavers, the transverse carpal ligament was transected
      completely without injury to any surrounding structures. With further
      investigation, this novel technique may offer a less invasive, office-based
      method for the surgical treatment of carpal tunnel syndrome that may offer
      patients an expedited recovery.

PMID- 15985792
TI  - Evaluation of genitofemoral nerve donor site morbidity after radical
      prostatectomy.
AB  - BACKGROUND: The sural nerve is commonly used as a donor site for cavernous nerve
      grafting. However, the genitofemoral nerve is accessible and easily dissected and
      may represent an improved donor site for this procedure. METHODS: Fourteen
      patients underwent radical prostatectomy followed by cavernous nerve grafting
      using the genitofemoral nerve. Seventeen donor sites (3 patients underwent
      bilateral grafts) were assessed by questionnaires (including the McGill Pain
      Scale) and focused neurologic examination. RESULTS: Residual numbness in the
      genitofemoral nerve distribution was noted in 9 of 17 donor sites (53%). No
      patients reported that the deficits interfered with normal daily activities. All
      patients denied the presence of burning, cold sensitivity, or pain. All patients
      scored 0 on each of the 3 pain rating components of the short form McGill Pain
      questionnaire (sensory, affective, or total). Furthermore, no patients documented
      pain on either the PPI or VAS portions of the questionnaire. On examination,
      patients were unable to discriminate between sharp versus dull stimuli in 3 donor
      sites (17.6%), while 7 donor sites (41.2%) showed decreased light-touch
      sensation. The Semmes-Weinstein testing demonstrated that 8 (47.1%) were found to
      have distinct areas with sensory deficit ranging in size from 23 to 63 cm (mean,
      16.6 cm). The highest-pressure thresholds for each of the 17 donor sites ranged
      from 3.61 to 6.45 g/mm (mean, 4.91 g/mm). The mean pressure threshold for the
      control regions (n=11) was 3.35 g/mm (range, 2.38--4.71 g/mm, P=0.014). Only 50%
      of the sensory deficits documented by the Semmes-Weinstein test were clinically
      apparent to the patients. CONCLUSIONS: Due to its low donor site morbidity, the
      genitofemoral nerve is an excellent donor source for cavernous nerve grafting
      during radical prostatectomy. In the majority of the patients, the sensory
      deficit produced by resection of this nerve is minimal and caused no other
      adverse symptoms. Harvest of this nerve prevents the additional morbidity
      associated with a donor site located elsewhere on the body (ie, sural nerve).

PMID- 15985793
TI  - The role of recipient sites in fat-graft survival: experimental study.
AB  - The survival of fat grafts depends on many factors, 1 of the major being early
      revascularization. Early studies showed that adipose tissue has a low tolerance
      to ischemia. Some methods have been described to increase the tolerance of
      adipose tissue to ischemia. This study was designed to compare volume maintenance
      of the transplanted fat graft in different recipient sites of the rabbit face.
      Three groups of 5 New Zealand white rabbits were studied. Fat grafts harvested
      from the right inguinal fat pad were transplanted to the buccomandibular area of
      the rabbit's face. Three different recipient sites (subcutaneous, supramuscular,
      and submuscular) were dissected on each side of the face, and groups were
      formulated based on this difference of recipient sites. Morphometric, as well as
      histopathologic, analyses were done, and the results revealed a statistically
      significant increase of fat graft survival in supramuscular layer (81.95% +/-
      4.40%) than in subcutaneous (41.62% +/- 3.29%) and submuscular layer (37.31% +/-
      5.77%) (P<0.05). This study demonstrates that selection of an "appropriate
      recipient site" should enhance ultimate fat-graft survival.

PMID- 15985794
TI  - Mechanical strain alters gene expression in an in vitro model of hypertrophic
      scarring.
AB  - Fibroblasts represent a highly mechanoresponsive cell type known to play key
      roles in normal and pathologic processes such as wound healing, joint
      contracture, and hypertrophic scarring. In this study, we used a novel fibroblast
      populated collagen lattice (FPCL) isometric tension model, allowing us to apply
      graded biaxial loads to dermal fibroblasts in a 3-dimensional matrix. Cell
      morphology demonstrated dose-dependent transition from round cells lacking stress
      fibers in nonloaded lattices to a broad, elongated morphology with prominent
      actin stress fibers in 800-mg-loaded lattices. Using quantitative real-time RT
      PCR, a dose dependent induction of both collagen-1 and collagen-3 mRNA up to 2.8-
      and 3-fold, respectively, as well as a 2.5-fold induction of MMP-1 (collagenase)
      over unloaded FPCLs was observed. Quantitative expression of the proapoptotic
      gene Bax was down-regulated over 4-fold in mechanically strained FPCLs. These
      results suggest that mechanical strain up-regulates matrix remodeling genes and
      down-regulates normal cellular apoptosis, resulting in more cells, each of which
      produces more matrix. This "double burden" may underlie the pathophysiology of
      hypertrophic scars and other fibrotic processes in vivo.

PMID- 15985795
TI  - Intermittent hydrostatic compression promotes nitric oxide production and
      osteodifferentiation of fetal dural cells.
AB  - PURPOSE: The aim of these studies was to evaluate the biologic response of fetal
      dural cell cultures to compressive mechanical force. METHODS: Primary cell
      cultures from the dura mater of E18 CD-1 mice were subjected to 2 PSI of
      intermittent hydrostatic compression (IHC) at a frequency of 0.5 Hz. Quantitative
      measures of the expression of Osterix (Osx), osteopontin (OP), endothelial nitric
      oxide synthase (eNOS) and Noggin were performed by RT-PCR following 3, 6, and 12
      hours of exposure to IHC. Nitric oxide production was quantified through the
      measurement of NO metabolites following 6 hours of exposure to IHC. RESULTS: IHC
      resulted in an increase in Osx, OP, and eNOS expression compared with controls at
      all time points. The expression of Noggin decreased at all time points. Exposure
      to IHC resulted in a significant increase in the production of NO metabolites at
      6 hours when compared with controls. CONCLUSIONS: These experiments indicate that
      dural cell biology is significantly altered following exposure to IHC.
      Specifically, IHC promotes production of NO and osteodifferentiation in fetal
      dural cell cultures, with increases in the expression of osteoinductive genes and
      decreases in inhibitors of osteogenesis.

PMID- 15985796
TI  - Lentiviral gene therapy with platelet-derived growth factor B sustains
      accelerated healing of diabetic wounds over time.
AB  - The treatment of diabetic wounds is a formidable clinical challenge. In this
      study, lentiviral vectors carrying the human platelet-derived growth factor B
      (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm x
      2.0-cm excisional wounds were created on the dorsa of genetically diabetic
      C57BL/KsJ-m+/+Lepr(db) mice. Lentiviral vectors containing the PDGF-B gene were
      injected into the wound margins and base. Mice were killed at 14-, 21-, and 35
      day intervals. Measurement of the residual epithelial gap showed a trend towards
      increased healing in lentiviral PDGF-treated wounds compared with untreated and
      saline-treated wounds at all time points. At 21 days, there was significantly
      increased healing in lentiviral PDGF-treated wounds (0.98+/-0.17 cm) compared
      with saline-treated wounds (1.22+/-0.30 cm; P<0.05). Immunohistochemistry for
      CD31 revealed significantly increased neovascularization in lentiviral PDGF
      treated wounds compared with untreated and saline-treated wounds at 14 and 21
      days (P<0.01). Picrosirius red staining demonstrated thicker and more highly
      organized collagen fibers in treated wounds compared with untreated and saline
      treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and
      2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline
      treated wounds, respectively (P<0.01). Lentiviral gene therapy with PDGF-B can
      sustain diabetic wound healing over time and may possess promising potential in
      the clinical setting.

PMID- 15985797
TI  - A comparison of resistance to fracture among four commercially available forms of
      hydroxyapatite cement.
AB  - Hydroxyapatite cement is a relatively new biomaterial that has found widespread
      use in craniomaxillofacial surgery. Despite its common usage, complication rates
      as high as 32% have been reported. When failed implants are removed, implant
      fracture has been cited as a potential cause of failure. The purpose of this
      study was to evaluate resistance to fracture among 4 commercially available
      hydroxyapatite cement formulations. The materials tested included Norian
      Craniofacial Repair System (carbonated apatite cement) (AO North America, Devon,
      PA), Norian CRS Fast Set Putty (carbonated apatite cement) (AO North America),
      BoneSource (hydroxyapatite cement) (Stryker Leibinger, Portage, MI), and Mimix
      (hydroxyapatite cement) (Walter Lorenz Surgical, Inc, Jacksonville, FL). To
      ensure consistency, all materials were embedded in acrylic wells. Each material
      was placed into a well 2.54 cm in diameter and 0.953 cm in thickness. The
      materials were prepared per manufacturer specifications. All materials were
      incubated at 37.0 degrees C, in 6% CO2, 100% humidity for 36 hours. Using the
      Bionix MTS Test System, a 12-mm-diameter probe applied incremental force to the
      center of the disk at a rate of 0.1 mm per second. The transmitted force was
      measured using a Bionix MTS Axial-Torsional Load Transducer for each disk. The
      force which resulted in fracture was recorded for each material. Ten disks of
      each material were processed by this method, for a total of 40 disks. The
      significance of resistance to fracture for the 4 compounds was analyzed using 1
      way analysis of variance with post hoc Scheffe method. Mean fracture force with
      related P values was plotted for direct comparison of group outcomes. Material
      type contributed significantly to variance in fracture force for the biomaterials
      studied. Norian CRS required the greatest mean fracture force (1385 N, SD+/-292
      N), followed by Norian CRS Fast Set Putty (1143 N, SD+/-193 N). Mimix required a
      mean fracture force of 740 N, SD+/-79 N. BoneSource required a mean fracture
      force of 558 N, SD+/-150 N. Mimix and BoneSource required significantly less
      force for fracture when compared with Norian CRS and Fast Set Putty (P<0.01).
      Comparisons of fracture load resistance between 4 commonly used bone substitute
      materials have not been previously reported. Increasing biomaterial strength may
      reduce complications resulting from reinjury to cranioplasty sites. In this
      model, Norian CRS and Norian CRS Fast Set Putty demonstrated a significantly
      greater resistance to fracture when compared with BoneSource and Mimix.

PMID- 15985799
TI  - The penile flap in the rat: description and autotransplantation.
AB  - Considering both its unique structural and functional properties, the
      reconstruction of the penis is still a challenging problem in reconstructive
      surgery. Reconstruction may be required in many situations, including traumas,
      congenital abnormalities, and female-to-male transsexual surgery. Currently, the
      only natural reconstructive method for the penis is its microvascular
      reattachment in amputation cases. In all other situations, and in nonreplantable
      amputations, there is no alternative but to reconstruct the penis using
      autologous tissues to create the most similar substitute, hoping for a possible
      allogeneic transplantation in the future. There are many unresolved issues and
      unanswered questions related to functional recovery after replantation of the
      penis. In this study, to overcome these drawbacks and to guide and show the
      feasibility of allogeneic transplantation of the penis in humans in the future,
      we describe a penile composite tissue flap based on the internal pudendal artery
      and its autotransplantation in an economical animal species. Fifty adult male
      Sprague-Dawley rats weighing 400 to 500 g were used. In 20 rats, the vascular
      anatomy of the male perineal region was determined by anatomic dissections. Based
      on this anatomic study, the penile composite flap was created based on the
      internal pudendal vessels. In 10 rats, the penile flap was raised as an island
      flap based on its vascular pedicle and replaced in situ. In 10 rats, distant flap
      transfer was accomplished to determine the feasibility of the flap being
      transferred as a free flap and to demonstrate the viability of the flap
      components in a heterotopic region. For this purpose, the flap was transferred to
      the groin region performing anastomoses between internal pudendal vessels and
      superficial epigastric vessels. In the control group (n=10), while the same
      surgical procedure was performed, the flap was transferred to the groin region
      but no anastomosis was performed. The procedure required approximately 3 to 4
      hours of operating time in the free flap group. Five of the animals died in the
      early postoperative days, while all others survived. Direct observation and
      microangiography were used to assess the viability of the flaps. On the basis of
      direct observation on the seventh postoperative day, all the pedicled flaps
      survived completely. In the free-flap group, all but 1 of the vascularized flaps
      showed complete survival, whereas all the nonvascularized flaps completely
      necrosed. The authors conclude that the penile flap of the rat offers the
      following advantages: (1) the composite tissue flap is harvested from a small
      animal species, (2) the flap is an exact representation of the clinical original
      penile composition, (3) it can be transferred as a free flap without the need for
      an isogeneic animal, (4) the vascular pedicle is consistent and allows for
      microvascular anastomoses. The flap will provide a means for future physiological
      studies, especially for replantation cases. The feasible autotransplantation of
      the penile flap with successful results will also guide researchers towards the
      future allogeneic transfer of the penis in humans.

PMID- 15985801
TI  - Analysis of skin-graft loss due to infection: infection-related graft loss.
AB  - This prospective study was performed to analyze the causes of infection-related
      skin-graft loss in a general population of plastic and reconstructive surgery
      patients. One hundred thirty-two patients who received either full- or split
      thickness skin grafts to reconstruct soft-tissue defects were included. The
      tissue defects were grouped according to the cause as follows: vascular ulcers
      (9.2%), burns (14.5%), traumatic tissue defects (36.6%), and flap donor-site
      defects (39.7%). In all cases, the preoperative evaluation indicated an adequate
      wound-bed preparation. However, graft loss secondary to infection was recorded in
      31 patients (23.5%). The microbiological cultures revealed Pseudomonas aeruginosa
      in 58.1% of the cases (P<0.05), followed by Staphylococcus aureus, Enterobacter,
      enterococci, and Acinetobacter; 58.3% of grafts in vascular ulcers, 47.4% of
      grafts in burns, 16.7% of grafts in traumatic-tissue defects; and 13.5% of grafts
      in donor-site defects were lost due to infection. Vascular ulcers and burns were
      more commonly associated with graft losses due to infection than other tissue
      defects (P<0.001). No correlation was found between the etiological cause of the
      defects and the microorganisms cultured. However, Pseudomonas infections were
      more fulminant and caused an increased reoperation rate 4.2 times (P<0.05). Full
      thickness grafts were more resistant to infection than split-thickness grafts
      (P<0.05). Graft loss due to infection was also more common in grafts applied to
      the lower extremities or when performed at multiple sites. In conclusion, 23.7%
      of skin grafts were lost due to infection in a group of general plastic surgery
      patients. Infection-related graft loss was more commonly encountered in vascular
      ulcers and burn wounds, and the most common cause was Pseudomonas aeruginosa.

PMID- 15985802
TI  - Mycobacteria abscessus outbreak in US patients linked to offshore surgicenter.
AB  - We recently encountered 5 patients with Mycobacterium abscessus infection
      following cosmetic procedures performed at a surgicenter located off the United
      States coastline which, by report, actively recruits domestic patients.
      Additional patients with similar clinical histories and presentation have been
      identified at other practices along the Eastern seaboard as well. A recent
      Centers for Disease Control and Prevention investigation has confirmed a common
      link. All procedures were performed in Santo Domingo, Dominican Republic, between
      2003 and 2004. More than half were performed at the same facility. We report
      herein a series of patients presenting with M. abscessus infections who underwent
      cosmetic surgery offshore. The goal of this manuscript is to heighten awareness
      among physicians who may encounter such patients in their practices. The indolent
      clinical presentation, laboratory studies utilizing acid-fast stains and
      cultures, and treatment including surgical debridement and pharmacologic regimens
      in the ultimate diagnosis and therapy for M. abscessus infections are discussed.

PMID- 15985805
TI  - Re: iatrogenic peripheral nerve lesions.

PMID- 15985806
TI  - Re: nipple reconstruction: the top hat technique.

PMID- 15985807
TI  - Re: consecutive versus simultaneous bilateral carpal tunnel release.

PMID- 15985809
TI  - Tissue necrosis following a honey bee sting.

PMID- 15985810
TI  - Re: the preputium: an overlooked skin graft donor site.

PMID- 15985812
TI  - Epidemiology of hypersensitivity drug reactions.
AB  - PURPOSE OF REVIEW: Hypersensitivity drug reactions are but one of the many
      different types of adverse drug reactions. They may be potentially life
      threatening, prolong hospitalization, affect drug prescribing patterns of
      physicians and result in socioeconomic costs. This review summarizes current
      knowledge on the incidence, prevalence, mortality and risk factors for these
      reactions in different populations. RECENT FINDINGS: Hypersensitivity reactions
      represent about one third of all adverse drug reactions. Adverse drug reactions
      affect 10-20% of hospitalized patients and more than 7% of the general
      population. Severe reactions including anaphylaxis, drug hypersensitivity
      syndromes, Stevens Johnson syndrome and toxic epidermal necrolysis are also
      associated with significant morbidity and mortality. Although several risk
      factors have been identified, their clinical importance has not been fully
      understood. Future progress in immunogenetics and pharmacogenetics may help
      identify populations at risk for specific types of reactions. SUMMARY: Well
      designed epidemiological studies on hypersensitivity drug reactions are lacking
      as most studies have been on adverse drug reactions. Such studies will be helpful
      in identifying patients at risk of developing such reactions, in particular
      severe reactions, and implementing early preventive measures.

PMID- 15985813
TI  - Histopathology of drug-induced exanthems: is there a role in diagnosis of drug
      allergy?
AB  - PURPOSE OF REVIEW: Cutaneous eruptions are among the most common adverse drug
      reactions and may often represent a challenging diagnostic problem. This review
      focuses on histopathological and immunohistochemical findings of drug-induced
      maculo-papular exanthems and discusses the value of skin biopsies and consequent
      histopathological examination in the diagnosis of these reactions. RECENT
      FINDINGS: Data from immunohistological studies indicate that CD4+ T cells
      expressing cytotoxic granule proteins such as perforin and granzyme B are
      critically involved in the pathogenesis and contribute to the generation of
      typical histopathological features of drug-induced maculo-papular exanthems, i.e.
      an interface dermatitis with vacuolar alteration and some apoptotic basal
      keratinocytes. In addition, an upregulation of both type 1 (i.e. IFN-gamma, TNF
      alpha) and type 2 (i.e. IL-5) cytokines has been reported. IL-5 together with
      other chemokines (i.e. eotaxin/CCL-11) provides an explanation for tissue
      eosinophilia, which may be suggestive of a drug eruption if present. SUMMARY:
      There are no absolute histological or immunohistological criteria for the
      diagnosis of drug-induced maculo-papular exanthems and even if the observed
      histological changes are compatible with a drug-induced eruption, biopsy may not
      definitely exclude alternative causes since there is considerable overlap with
      features seen in other entities. In mild cases with no severe signs or symptoms
      and a clear temporal relationship, clinical information and the morphologic
      pattern of skin lesions are often sufficient for diagnosis. However, in complex
      and severe cases or when the precise morphology is unclear, histopathological
      findings may provide some clues and assist in reaching a correct diagnosis.

PMID- 15985814
TI  - Cephalosporin chemical reactivity and its immunological implications.
AB  - PURPOSE OF REVIEW: The aim of this article is to analyze the chemical reactivity
      of cephalosporins resulting in the epitope responsible for recognition by IgE
      antibodies and to establish the basis of the allergenicity. RECENT FINDINGS:
      Increasing evidence supports the role of cephalosporins in IgE hypersensitivity
      reactions. Third and fourth generation cephalosporins appear to be more involved
      in specific IgE reactions and often no cross-reactivity with traditional benzyl
      penicillin determinants exists. In some instances selective responses to unique
      cephalosporins occur and in others common side-chain similarities exist. SUMMARY:
      Lack of knowledge of the exact chemical structure of cephalosporin antigenic
      determinants has hindered clinical interpretation of allergic reactions to these
      drugs and hampered understanding of the specific recognition by IgE molecules of
      these determinants. Data indicate that R2 is not present in the final conjugate
      and that recognition by IgE antibodies is mainly directed to the R1 acyl side
      chain and to the beta-lactam fragment that remains linked to the carrier protein
      in the cephalosporin conjugation process.

PMID- 15985815
TI  - Murine models of drug hypersensitivity.
AB  - PURPOSE OF REVIEW: Drug hypersensitivity reactions are relatively rare but may
      result in severe morbidity and fatalities. Due to the idiosyncratic nature and
      multifactorial etiology of these reactions, development of a single animal model
      to study the immunosensitizing mechanisms of all drugs is impossible. This
      hampers the development of predictive screening models that are urgently needed
      to assess the immunostimulating capacity of newly developed drugs. The present
      review will focus on recent findings on mechanisms of drug hypersensitivity
      reactions obtained with murine models, and on the use of these models as
      potential screening tools to assess the immunostimulating capacity of drugs.
      RECENT FINDINGS: Mechanisms of drug-induced sensitization versus tolerance appear
      dependent on generally accepted immunological paradigms. For instance, co
      stimulatory signaling by antigen-presenting cells is decisive in drug-induced
      immunosensitization and both T cells and antigen-presenting cells are important
      for the induction of tolerance to orally administered drugs. From recent studies
      it has been hypothesized that expression of stress-associated transcription
      factors and the expression of costimulatory molecules or cytokine production
      within hours or days after the initial exposure may be representative of drug
      induced hypersensitivity reactions and may thus be used as predictive parameters
      to screen for immunosensitizing drugs. SUMMARY: The development of animal models
      to study mechanisms of drug hypersensitivity reactions is still in its infancy.
      Much effort has been made, however, to search for early indicators of
      immunostimulation in murine animal models that may eventually appear useful in a
      tiered strategy to assess drug-induced sensitization.

PMID- 15985816
TI  - Avoidance of bee and wasp stings: an entomological perspective.
AB  - PURPOSE OF REVIEW: Clinicians and researchers in allergy and immunology are often
      unaware of aspects of stinging insect biology that would be of practical interest
      to their patients. This review discusses entomological literature pertaining to
      avoidance of bee and wasp stings, with emphasis on risk factors associated with
      provoking individual foragers versus disturbing colonies and preventive measures
      for both circumstances. RECENT FINDINGS: Recent work pertaining to sting
      avoidance has mostly been concerned with the development and testing of
      attractants, insecticides and delivery systems for toxic baiting programs to
      control vespine wasps. SUMMARY: Sting risks and avoidance measures associated
      with bee and wasp foragers are different from those posed by disturbing colonies.
      Despite widespread advice to the contrary, no evidence currently exists that
      wearing perfume or bright, floral-colored clothing elevates sting risk. Foragers
      usually have to be firmly touched before they will sting; therefore, personal
      protection largely involves guarding against accidental direct contact. Although
      still under development, the most effective means for reducing local populations
      of foraging vespine wasps are toxic baiting programs. Preventing stings from
      colonies is more problematic and depends mostly on personal awareness when
      disturbing vegetation. The most effective measure in mitigating the severity of a
      mass attack is probably the wearing of white or light-colored clothing.

PMID- 15985817
TI  - Bee venom allergy in beekeepers and their family members.
AB  - PURPOSE OF REVIEW: To analyze prevalence of allergic sting reactions, including
      the clinical and diagnostic features as well as management options in a
      population heavily exposed to honeybee stings such as beekeepers and their family
      members. RECENT FINDINGS: The higher sting frequency is associated with an
      increased prevalence of allergic sting reactions. Major risk factors for allergic
      sting reactions in beekeepers are: fewer than 10 annual stings, an atopic
      constitution and symptoms of upper respiratory allergy during work in the
      beehive. Bee venom allergic beekeepers have higher levels of bee venom-specific
      IgG but lower skin sensitivity and bee venom-specific IgE than normally exposed
      bee venom allergic patients. Safety of bee venom immunotherapy is higher in
      beekeepers than in allergic controls, while efficacy of this treatment is similar
      in both groups. SUMMARY: Beekeepers and their family members are at an increased
      risk of severe sting anaphylaxis and therefore need especially careful
      instruction with regard to avoidance of re-exposure, emergency treatment and
      specific immunotherapy with bee venom.

PMID- 15985818
TI  - Clinical reactivity to insect stings.
AB  - PURPOSE OF REVIEW: Allergy to insect stings remains a hazard worldwide and is the
      object of updated guidelines on management. This paper reviews the various
      clinical responses that may occur following an insect sting. RECENT FINDINGS:
      Although the general population is at slight risk, certain groups are more
      susceptible, including occasionally stung adult male agricultural workers, hobby
      honey beekeepers and family members of beekeepers. Individuals with systemic
      mastocytosis are especially reactive to stings. The body of evidence attesting to
      the marked beneficial effect that 3-5 years of venom immunotherapy has on the
      natural history of hymenoptera hypersensitivity is especially evident in
      children. Case reports indicate other consequences of hymenoptera sting, and
      these are discussed. SUMMARY: Hypersensitivity to insect stings is common and may
      be life threatening. Although most occur away from medical facilities, their
      diagnosis and management are important to a wide spectrum of health care
      professionals. Most reactions to stings are nonallergic manifestations of the
      venom's toxic effects, and present as erythema, pain and swelling about the sting
      site. Fire ants bite with their mandibles and pivot their head, inflicting
      multiple stings that usually result in a sterile pseudopustule at the site.
      Hypersensitivity responses to venom range from large local reactions (a late
      phase response) to life-threatening anaphylaxis. Venom-specific immunotherapy is
      highly effective in the modification of subsequent reactions to hymenoptera
      stings, as is whole body extract for fire ant stings.

PMID- 15985819
TI  - Unusual reactions to insect stings.
AB  - PURPOSE OF REVIEW: A variety of unusual or unexpected reactions have occurred in
      a temporal relationship to insect stings. This review will summarize these case
      history reports in recent years. As these reactions are very infrequent, the
      review will also include prior reported unusual reactions attributed to insect
      stings. RECENT FINDINGS: Acute encephalopathy occurred 8 days after yellow jacket
      stings, without any other obvious cause. There have been prior reports of other
      neurological reactions, myasthenia gravis, peripheral neuritis and Guillain-Barre
      syndrome related to insect stings. Acute renal failure with tubular necrosis has
      occurred following massive numbers of stings from Africanized honeybees.
      Nephrotic syndrome has been reported in the past following single stings. Silent
      myocardial infarction has occurred, probably related to acute anaphylactic
      symptoms immediately following a sting. There are recent reports of other
      pathology, diffuse alveolar hemorrhage and rhabdomyolysis and prior reports of
      thrombocytopenic purpura and vasculitis. As the result of ocular stings, local
      reactions have occurred with corneal pathology leading to cataracts. Other prior
      reported reactions to ocular stings include conjunctivitis, corneal infiltration,
      lens subluxation, and optic neuropathy. There is scarce information regarding the
      pathogenesis of the majority of the unusual reactions and the subsequent allergic
      status or risk for sting anaphylaxis of people who have had these unusual
      reactions. SUMMARY: This review includes a variety of reactions, particularly
      involving neurological, renal and cardiovascular symptoms, related to insect
      stings. It is important that clinicians be aware of this relationship when
      assessing people with these reactions and address future prophylaxis.

PMID- 15985820
TI  - Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis.
AB  - PURPOSE OF REVIEW: Anaphylactic cardiovascular collapse can be resistant to
      treatment with epinephrine (adrenaline) and, in some cases, diagnostic
      uncertainty compromises follow-up care. The purpose of this review is to examine
      recent studies relevant to the management and diagnosis of this condition. RECENT
      FINDINGS: Nausea, vomiting, incontinence, diaphoresis, dyspnoea, hypoxia,
      dizziness and collapse are associated with hypotension. Relative bradycardia
      (falling heart rate despite hypotension) is a consistent feature of hypotensive
      insect sting anaphylaxis and may represent a non-specific physiological response
      to severe hypovolaemia in conscious individuals. Upright posture has been found
      to be associated with death from anaphylaxis. Animal studies have found the
      intramuscular route for epinephrine is ineffective, intravenous boluses
      temporarily effective, but intravenous infusions of epinephrine are able to
      reverse anaphylactic shock. In one animal model, antihistamines were found to be
      harmful. A prospective human study provides evidence for the efficacy of
      treatment with intravenous epinephrine infusion and fluid (volume) resuscitation.
      Case reports support the use of the vasoconstrictors metaraminol, methoxamine and
      vasopressin if adrenaline is ineffective. Repeated measurements of mast cell
      tryptase are more sensitive and specific than a single measurement for the
      diagnosis of anaphylaxis. SUMMARY: Current evidence supports use of the
      supine/Trendelenburg position, epinephrine by intravenous infusion and aggressive
      volume resuscitation. If these fail, atropine should be considered for severe
      bradycardia and potent vasoconstrictors may be useful. To confirm the diagnosis
      of anaphylaxis, serial measurements of mast cell tryptase may be preferable to a
      single measurement.

PMID- 15985821
TI  - Are regulatory T cells the target of venom immunotherapy?
AB  - PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only treatment that
      leads to lifelong tolerance to previously disease-causing allergens by restoring
      normal immunity against allergens. T-regulatory (TReg) cells are involved in
      preventing sensitization to allergens and represent a major target for venom- or
      other allergen-specific immunotherapy. RECENT FINDINGS: Induction of peripheral
      tolerance in T cells, which is characterized mainly by suppressed proliferative
      and cytokine responses against the T-cell epitopes of major allergens, is an
      essential step in specific immunotherapy. It is initiated by the autocrine action
      of interleukin-10 and/or transforming growth factor-beta, which are produced by
      antigen-specific TReg cells. Tolerized T cells can be reactivated to produce
      distinct T-helper-1 or T-helper-2 cytokine patterns, thus directing allergen
      specific immunotherapy toward successful or unsuccessful outcomes. TReg cells
      directly or indirectly influence effector cells of allergic inflammation, such as
      mast cells, basophils and eosinophils. In addition, there is accumulating
      evidence that they may suppress IgE production and induce IgG4 and IgA production
      against allergens. In addition, histamine released from mast cells and basophils
      may efficiently contribute to immunoregulation during specific immunotherapy, and
      affect TReg cells and the production of their cytokines via histamine receptor 2.
      SUMMARY: By applying recent knowledge in TReg-cell-dependent mechanisms of
      peripheral tolerance, more rational and safer approaches to the prevention and
      cure of venom hypersensitivity may be developed in the future.

PMID- 15985822
TI  - Bibliography. Current world literature. Drug allergy.

PMID- 15985824
TI  - Outbreaks of viral gastroenteritis: what's new in 2004?
AB  - PURPOSE OF REVIEW: Descriptions of outbreaks of viral gastroenteritis have become
      a prominent feature in scientific journals and other media such as the electronic
      reporting service 'promed'. A review of outbreak reports was done to further our
      understanding of the burden of disease, common and rare modes of transmission,
      complications, and possibilities for control and prevention. RECENT FINDINGS:
      Viral gastroenteritis outbreaks occur worldwide. In 2004, besides outbreak
      reports and surveys, there was considerable attention paid to food and waterborne
      outbreaks and the difficulties in proving these modes of transmission. Costs of
      viral gastroenteritis outbreaks are high. Complications and unusual
      manifestations of viral gastroenteritis, such as convulsions, transplant
      rejection, and chronic infection, may have been underreported. SUMMARY: Viral
      gastroenteritis is a very common illness in health care settings that can cause
      significant disruption. Clinicians working in these settings should be familiar
      with the epidemiology and the possible modes of transmission of enteric viruses
      to be able to translate them into strategies for prevention or intervention.
      Research is needed to support these strategies.

PMID- 15985825
TI  - Vancomycin-resistant staphylococci and enterococci: epidemiology and control.
AB  - PURPOSE OF REVIEW: This review updates information on the development and spread
      of vancomycin resistance in staphylococci and enterococci. RECENT FINDINGS: New
      information on the genetic characterization of vancomycin-resistant
      Staphylococcus aureus isolates from the US indicates that each of the four was
      the result of an independent genetic event. New data suggest that vancomycin
      intermediate S. aureus isolates, particularly those showing heteroresistance, are
      clinically significant. Finally, vancomycin-resistant enterococci continue to be
      reported from around the world. Novel infection control measures, however, may
      aid in reducing the spread of these organisms in healthcare settings. SUMMARY:
      The exchange of genetic information, particularly the vanA gene, between and
      among staphylococci and enterococci will continue to challenge physicians,
      microbiologists, and infection control practitioners in efforts to identify,
      treat, and prevent infections with these pathogens.

PMID- 15985826
TI  - Update on Pseudomonas aeruginosa and Acinetobacter baumannii infections in the
      healthcare setting.
AB  - PURPOSE OF REVIEW: Infections with Pseudomonas aeruginosa and Acinetobacter
      baumannii are of great concern for hospitalized patients, especially with
      multidrug-resistant strains. This review focuses on recent data that may help us
      to understand the emergence, spread, and persistence of antibiotic resistance,
      and summarizes the optional treatment feasible for these resistant bacteria.
      RECENT FINDINGS: Multidrug-resistant P. aeruginosa and A. baumannii are
      increasingly causing nosocomial infections; multidrug-resistant clones are
      spreading into new geographic areas, and susceptible strains are acquiring
      resistance genes. New extended-spectrum beta-lactamases and carbapenemases are
      emerging, leading to pan-resistant strains. Current studies focus on the effect
      of antibiotics on gene expression in P. aeruginosa biofilms and their
      contribution to resistance to therapy. Treatment options for multidrug-resistant
      P. aeruginosa and A. baumannii infections are limited in most cases to
      carbapenems. Sulbactam is a treatment option for pan-resistant A. baumannii, and
      or renewed use of an old drug, colistin, is being entertained for pan-resistant
      A. baumannii and P. aeruginosa. Immunotherapy is a promising new modality being
      explored. Prevention of emergence of resistance through combination therapy and
      pharmacokinetic strategies are studied. SUMMARY: The emergence and spread of
      multidrug-resistant P. aeruginosa and A. baumannii and their genetic potential to
      carry and transfer diverse antibiotic resistance determinants pose a major threat
      in hospitals. The complex interplay of clonal spread, persistence, transfer of
      resistance elements, and cell-cell interaction contribute to the difficulty in
      treating infections caused by these multidrug-resistant strains. In the absence
      of new antibiotic agents, new modalities of treatment should be developed.

PMID- 15985827
TI  - Changing face of health-care associated fungal infections.
AB  - PURPOSE OF REVIEW: The purpose of this review was to evaluate recent publications
      on the epidemiology, diagnosis and management of invasive fungal infections.
      RECENT FINDINGS: Epidemiological surveys have highlighted significant differences
      between Europe and the United States regarding the incidence and etiology of
      Candida bloodstream infections. Today, invasive aspergillosis is occurring in a
      much broader patient population than the classical immunocompromised hosts and
      includes mechanically ventilated intensive care unit patients and patients
      receiving corticosteroids for treatment of chronic lung diseases. Diagnosis is
      often delayed in these patients and prognosis is dismal. Measurement of
      galactomannan, mannan and antimannan antibodies, and beta-(1-3)-D-glucan may help
      to speed up diagnosis. The epidemiology of invasive mold infections is changing.
      The frequency of non-fumigatus Aspergillus species is increasing, uncommon hyalo
      or phaeo-hyphomycoses are emerging and breakthrough mold infections intrinsically
      resistant to azoles have been reported. Clinical trials have shown that new
      azoles and echinocandins are as efficacious as amphotericin B or fluconazole for
      the treatment of eosophageal or invasive candidiasis, for prophylaxis of invasive
      fungal infections in transplant patients, or for empirical antifungal therapy in
      patients with persistent fever and neutropenia. SUMMARY: Recent data suggest that
      the epidemiology of invasive fungal infections may be changing with the emergence
      of uncommon molds and the occurrence of invasive aspergillosis in 'nonclassical'
      immunocompromised hosts. New diagnostic tools and improved antifungal agents are
      available to facilitate early diagnosis and offer new treatment options.

PMID- 15985828
TI  - Hospital disinfection: efficacy and safety issues.
AB  - PURPOSE OF REVIEW: To review recent publications relevant to hospital
      disinfection (and cleaning) including the reprocessing of medical instruments.
      RECENT FINDINGS: The key question as to whether the use of disinfectants on
      environmental surfaces rather than cleaning with detergents only reduces
      nosocomial infection rates still awaits conclusive studies. New disinfectants,
      mainly peroxygen compounds, show good sporicidal properties and will probably
      replace more problematical substances such as chlorine-releasing agents. The safe
      reprocessing of medical devices requires a well-coordinated approach, starting
      with proper cleaning. New methods and substances show promising activity for
      preventing the transmission of prions. Different aspects of virus inactivation
      have been studied, and the transmissibility, e.g. of norovirus, shows the need
      for sound data on how different disinfectant classes perform. Biofilms or other
      forms of surface-adherent organisms pose an extraordinary challenge to
      decontamination. Although resistance to biocides is generally not judged to be as
      critical as antibiotic resistance, scientific data support the need for proper
      use, i.e. the avoidance of widespread application, especially in low
      concentrations and in consumer products. SUMMARY: Chemical disinfection of heat
      sensitive instruments and targeted disinfection of environmental surfaces are
      established components of hospital infection control. To avoid danger to staff,
      patients and the environment, prudent use as well as established safety
      precautions are required. New technologies and products should be evaluated with
      sound methods. As emerging resistant pathogens will challenge healthcare
      facilities in the future even more than at present, there is a need for well
      designed studies addressing the role of disinfection in hospital infection
      control.

PMID- 15985829
TI  - Recent advances in epidemiology and prevention of gastrointestinal endoscopy
      related infections.
AB  - PURPOSE OF REVIEW: This article reviews recent publications relevant to endoscope
      reprocessing and the potential for transmission of infection during
      gastrointestinal endoscopy. RECENT FINDINGS: There have been a number of
      established reprocessing failures of gastrointestinal endoscopes at various
      healthcare facilities across the US resulting in patient notifications. These
      episodes have been associated with user errors and reprocessing equipment
      failures, highlighting the need for increased compliance with established
      guidelines. Surveillance cultures may be useful to monitor the outcome of
      reprocessing, although their use is controversial. New technology to allow point
      of-use monitoring is promising. Biofilm accumulation may be an issue when
      reprocessing gastrointestinal endoscopes. Although peracetic acid has been
      promoted as superior to aldehyde-type liquid chemical germicides with regard to
      soil fixation, it may only be a modest improvement. Electrolyzed acid water is an
      emerging liquid chemical germicide that may be equivalent to currently accepted
      disinfectants. There appears to be no benefit to an additional reprocessing cycle
      before use for endoscopes that have been appropriately cleaned, disinfected, and
      stored. SUMMARY: With the recent media attention on gastrointestinal endoscope
      reprocessing failures, despite the absence of documented transmission of
      infection, increased compliance with existing guidelines and new initiatives to
      enhance endoscope reprocessing are increasingly important to maintain public
      confidence.

PMID- 15985830
TI  - Protection of healthcare workers from bloodborne pathogens.
AB  - PURPOSE OF REVIEW: For decades, healthcare workers have been known to be at risk
      from acquiring a variety of bloodborne pathogen infections as a result of
      occupational exposure. Primary prevention of exposures, as recommended by
      universal precautions guidelines, remains the cornerstone of protecting
      healthcare workers. Nonetheless, a substantial number of parenteral exposures
      continue to occur. Updated developments are summarized here, and recommendations
      for the protection of healthcare workers from bloodborne pathogens are provided.
      RECENT FINDINGS: The predominant evidence suggests that total percutaneous
      injuries have decreased over the last decade. Thoughtful adherence to universal
      precautions remains the primary means of preventing occupational exposures and
      thus of reducing occupational risk of infection with bloodborne pathogens. A
      number of studies have provided additional evidence for the efficacy of safety
      devices in reducing specific subsets of injuries when combined with education and
      administrative interventions. Barriers to and positive predictors of universal
      precautions compliance have been identified. Postexposure prophylaxis remains the
      second line of defense; several authorities have now recommended three
      antiretroviral agents in this setting. SUMMARY: In summary, almost two decades of
      experience with universal/standard precautions has resulted in a decrease in
      parenteral injuries, but much work remains to be done. Vaccines, effective
      infection control procedures, safer procedures, and safer devices will all be
      necessary, along with a better understanding of factors that influence healthcare
      worker behaviors that result in injury. In addition, a number of issues relating
      to the postexposure management of occupational exposures with bloodborne
      pathogens need to be better understood.

PMID- 15985831
TI  - Emerging viral infections in transplant recipients.
AB  - PURPOSE OF REVIEW: Transplant patients are uniquely predisposed to emerging
      infections for a number of reasons. Two outbreaks, West Nile virus and severe
      acute respiratory syndrome, have recently provided important lessons on how
      transplant patients are affected, and how transplant programmes must adapt and
      evolve in the face of emerging infections. An update of emerging infections in
      transplant patients, using West Nile virus and severe acute respiratory syndrome
      as specific examples, is summarized here. RECENT FINDINGS: Exogenous
      immunosuppression, specific allograft factors, and extensive contact with the
      healthcare system all predispose transplant patients to emerging infections.
      Transplant patients may acquire West Nile virus through blood transfusion, donor
      transmission, or community exposure. Seroprevalence data in transplant
      populations suggest the risk of severe neurological disease is several fold
      higher in transplant recipients who acquire West Nile virus compared with
      immunocompetent individuals. Prevention strategies are critical in this
      population. These include nucleic acid testing of blood products and potentially
      also screening organ donors in a similar manner. During the outbreak of severe
      acute respiratory syndrome, transplant patients with severe and rapidly
      progressive disease were reported. Higher viral burdens appeared to be present in
      transplant patients and may have implications for the increased infectivity of
      these patients. Transplant programmes in severe acute respiratory syndrome areas
      were also adversely affected because of donor concerns, recipient issues and
      resource problems. SUMMARY: Transplant patients are uniquely predisposed to
      emerging infections. Lessons learned from West Nile virus and severe acute
      respiratory syndrome in transplantation should be applicable to future outbreaks
      of other emerging infectious diseases.

PMID- 15985832
TI  - Infectious complications in organ transplant recipients with the use of
      calcineurin-inhibitor agent-based immunosuppressive regimens.
AB  - PURPOSE OF REVIEW: The rates and types of infections associated with conventional
      immunosuppression regimens comprising calcineurin-inhibitor agents, tacrolimus,
      and cyclosporine could be used to compare similar data with the use of novel
      immunosuppressive regimens in organ transplant recipients. RECENT FINDINGS:
      Tacrolimus appears to be superior to cyclosporine in preventing rejection. The
      frequency and spectrum of infections in organ transplant recipients does not
      appear to be notably modified by the choice of calcineurin-inhibitor agents per
      se. A higher risk of cytomegalovirus and poorer outcomes associated with
      hepatitis C virus with cyclosporine in some studies may be related to a greater
      requirement of adjunctive immunosuppression with cyclosporine-based regimens.
      Potent immunosuppression with tacrolimus, however, particularly when combined
      with mycophenolate mofetil, is believed to be a significant contributor to a
      higher incidence of BK virus nephropathy in renal transplant recipients in recent
      years. Calcineurin-inhibitor agents possess in-vitro activity against a number of
      fungal pathogens. In the clinical setting, however, the immunosuppressive effect
      outweighs their antifungal activity. SUMMARY: Calcineurin inhibitor-based
      regimens have been the mainstay of immunosuppression after organ transplantation
      for almost two decades. However, suboptimal long-term outcomes in transplant
      recipients have led to a growing interest in the use of calcineurin inhibitor
      agent-sparing regimens. Whether novel immunosuppressive agents with a more
      selective mechanism of action would lead to a further reduction in the risk of
      posttransplant infections remains to be discerned.

PMID- 15985833
TI  - The influence of the conditions of hematopoietic cell transplantation on
      infectious complications.
AB  - PURPOSE OF REVIEW: The multitude of factors that influence the risk of infection
      after hematopoietic cell transplantation has been further complicated by the
      rapid evolution of this therapy in the past 5 years. The degree to which
      functional immune reconstitution has been achieved reflects the equilibrium
      reached by the immune systems of the recipient and donor in the context of host
      non-hematopoietic tissue. Thus immunomodulatory influences on the recipient and
      the transplanted graft, both before and after hematopoietic cell transplantation,
      have a profound influence on the incidence and severity of infection. This review
      of the recent literature contributes to our understanding of how the conditions
      of hematopoietic cell transplantation influence the timing and nature of
      infectious complications. RECENT FINDINGS: The main themes of published primary
      research from 2004 to the present focus on non-myeloablative conditioning
      regimens and their effects on immune reconstitution after hematopoietic cell
      transplantation. SUMMARY: A plethora of clinical trials are ongoing, focused on
      the outcome after conditioning regimens designed to result in less regimen
      related toxicity while preserving or enhancing the graft-versus-tumor effect.
      Given the infancy of these new approaches, it is not possible to make definitive
      statements regarding the relative risk of serious infection with each therapy. It
      is clear that a reduction in regimen-related non-infectious complications or
      mortality does not necessarily ensure a reduction in clinically significant
      infections. Improvements in early diagnostic and therapeutic options for these
      infections now bring us to an era of understanding pathogens as probes of the
      functional reconstitution of immunity.

PMID- 15985834
TI  - Exogenous administration of immunomodulatory therapies in hematopoietic cell
      transplantation: an infectious diseases perspective.
AB  - PURPOSE OF REVIEW: In contrast to the recipient of a solid organ transplantation,
      the immunological competence of recipients of hematopoietic cell transplantation
      does not correlate well with the administration of non-corticosteroid
      immunosuppressive agents. This apparent paradox reflects the unique and dynamic
      conglomeration of factors that affect immune reconstitution after hematopoietic
      cell transplantation. The following is the second part of a review of the recent
      primary literature regarding exogenous immunomodulatory influences as they
      pertain to infections in the setting of hematopoietic cell transplantation.
      RECENT FINDINGS: The main themes of published primary research from 2004 to the
      present include the influence of exogenously administered immunomodulatory agents
      on infectious complications after hematopoietic cell transplantation. SUMMARY:
      The use of immunomodulatory agents such as monoclonal antibodies directed against
      lymphocyte antigens in the treatment of hematopoietic malignancy has greatly
      expanded during the past decade. Separate trials of the potential utility of
      these agents, particularly in the reduction of graft-versus-host disease, in the
      setting of hematopoietic cell transplantation have yielded encouraging results.
      Given the infancy of these new approaches, it is not possible to make definitive
      statements regarding the relative risk of serious infection with each therapy. It
      is clear that a reduction in regimen-related non-infectious complications or
      mortality does not necessarily ensure a reduction in clinically significant
      infections. Improvements in early diagnostic and therapeutic options for these
      infections now bring us to an era of understanding pathogens such as
      cytomegalovirus as probes of the functional reconstitution of immunity.

PMID- 15985835
TI  - Bibliography. Current world literature. Nosocomial and hospital related
      infections.

PMID- 15985837
TI  - Protective factors against suicidal behavior in Latinos.
AB  - Latinos appear to be relatively protected against suicidal behavior, but the
      factors that mediate this effect are not known. Some protective factors may be
      related to cultural constructs that provide a buffer against suicidal behavior in
      the face of psychiatric illness. We sought to determine whether the Reasons for
      Living Inventory (RFLI) might capture protective factors against suicidal
      behavior in Latinos and non-Latinos. Patients with major depression, bipolar
      disorder, or schizophrenia were interviewed regarding their depressive
      symptomatology and lifetime history of suicidal behavior. The RFLI, which
      measures protective factors against suicidal acts, was also administered.
      Multivariate analyses were used to assess the relationship between suicide
      measures, ethnicity, and selected clinical and demographic variables. Although
      Latinos and non-Latinos did not differ significantly in attempter status
      (attempter/nonattempter), number of attempts, or suicide intent, Latinos reported
      significantly less suicidal ideation and made less lethal attempts. On the RFLI,
      Latinos scored significantly higher on subscales regarding survival and coping
      beliefs, responsibility to family, and moral objections to suicide, possibly
      reflective of cultural norms endorsed by Latino groups. Multivariate analyses
      suggested that although being Latino was independently associated with less
      suicidal ideation, other suicidal behaviors held a stronger relationship to moral
      objections to suicide and survival and coping skills than to ethnicity. Self
      identification as Latino may be associated with espousing cultural constructs
      that mediate protective effects against suicidal behavior. Constructs identified
      in the RFLI may protect Latinos from acting on suicidal thoughts, affecting moral
      objections to suicide and survival and coping beliefs. Further studies to
      elucidate the impact of these factors on suicidal behavior and their relationship
      to specific cultural constructs would be of interest.

PMID- 15985838
TI  - Suicidal ideation and correlates in Taiwanese adolescent methamphetamine users.
AB  - The aim of this study was to evaluate the prevalence of suicidal ideation and its
      correlates in adolescent methamphetamine (MAMP) users. Using the Epidemiological
      Version of the Kiddie Schedule for Affective Disorders and Schizophrenia, 200
      adolescent MAMP users were assessed for suicidal ideation and psychiatric
      disorders during the preceding year. Demographic variables, family and peer
      interaction, characteristics of MAMP use, and personality were also evaluated.
      Factors correlating to suicidal ideation in adolescent MAMP users were analyzed
      by logistic regression. In the preceding year, 16% of adolescent MAMP users had
      suicidal ideation, and multiple factors, including illicit drug use among family
      members, depressive disorder, adjustment disorder, and emotional instability,
      correlated with suicidal ideation. Multiple factors, including family,
      psychopathology, and personality correlate with suicidal ideation in adolescent
      MAMP users. Subjects showing these characteristics should be monitored for
      suicidal ideation.

PMID- 15985836
TI  - Predictors of high rates of suicidal ideation among drug users.
AB  - Several studies have attempted to understand the link among substance abuse,
      depression, and suicidal ideation (SI). Assessment of this link is important to
      develop specific interventions for persons in substance abuse treatment. This
      association was tested among 990 drug users in and out of treatment with
      significant criminal justice histories from two National Institute on Drug Abuse
      studies. The Diagnostic Interview Schedule and Substance Abuse Module assessed
      DSM-III-R depression, number of depression criteria met, antisocial personality
      disorder (ASPD), and substance use disorders. Compared with men, women were twice
      as likely to report depression (24% vs. 12%), whereas men were nearly twice as
      likely to report ASPD (42% vs. 24%). High rates of SI were found, with women more
      likely than men to report thoughts of death (50% vs. 31%), wanting to die (39%
      vs. 21%), thoughts of committing suicide (47% vs. 33%), or attempting suicide
      (33% vs. 11%); 63% of women and 47% of men reported at least one of these
      suicidal thoughts or behaviors. Male and female ideators were more likely than
      nonideators to report depressed mood and to meet criteria for depression, ASPD,
      and alcohol use disorders. Male ideators were more likely than male nonideators
      to meet criteria for cocaine use disorders. Using logistic regression, SI among
      men was predicted by alcohol use disorder (OR = 1.60), ASPD (OR = 1.59), and
      number of depression criteria (OR = 9.38 for five criteria). Among women, SI was
      predicted by older age, marital status, alcohol use disorder (OR = 2.77), and
      number of depression criteria (OR = 9.12 for five criteria). These original
      findings point out the need to discuss suicidal thoughts among depressed drug
      users for early treatment and prevention.

PMID- 15985839
TI  - Anxiety disorders associated with suicidal ideation and suicide attempts in the
      National Comorbidity Survey.
AB  - This study examined the relationship between anxiety disorders and suicidal
      ideation or suicide attempts in a nationally representative sample (N = 5877;
      age, 15-54; response rate, 82.4%). A modified version of the Composite
      International Diagnostic Interview was used to make DSM-III-R mental disorder
      diagnoses. Two multivariate logistic regression analyses were performed with
      suicidal ideation (N = 754) and suicide attempts (N = 259) as dependent
      variables. In each regression, the independent variables entered were lifetime
      social phobia, panic disorder, agoraphobia, generalized anxiety disorder, simple
      phobia, and posttraumatic stress disorder (PTSD). Covariates in the analyses were
      sociodemographics, lifetime mood disorders, substance use disorders, nonaffective
      psychosis, antisocial personality disorder, and presence of three or more
      lifetime DSM-III-R diagnoses. PTSD was significantly associated with suicidal
      ideation (adjusted odds ratio = 2.79; p < 0.01) and suicide attempts (adjusted
      odds ratio = 2.67; p < 0.01). None of the other anxiety disorders were
      significantly associated with suicidal ideation or attempts. The robust
      association between PTSD and suicide attempts has important implications for
      psychiatric assessment of suicidal behavior. Future research is required to
      investigate the mechanisms underlying the relationship between PTSD and suicidal
      behavior.

PMID- 15985840
TI  - Adverse race-related events as a risk factor for posttraumatic stress disorder in
      Asian American Vietnam veterans.
AB  - Few studies have explored the relationship between exposure to adverse race
      related events and posttraumatic stress disorder (PTSD). This study examined
      whether adverse race-related events can give rise to symptoms that meet the
      criteria for a PTSD diagnosis as specified in the DSM-IV. Three hundred Asian
      American Vietnam veterans were administered a Mississippi Scale and a
      questionnaire that assessed exposure to adverse race-related events in the
      military and associated PTSD symptoms. A subsample was administered the Clinician
      Administered PTSD Scale. A majority of the participants (77%) reported exposure
      to adverse race-related events. Depending on the number of events to which they
      were exposed, between 13% and 36% reported symptoms consistent with meeting full
      criteria for PTSD. Mississippi Scale scores increased significantly as a function
      of frequency of exposure to adverse race-related events. These results converge
      with the Clinician-Administered PTSD Scale findings to demonstrate that adverse
      race-related events can be traumatic and associated with PTSD. These findings
      support the construct and convergent validity of race-related PTSD.

PMID- 15985841
TI  - Predicting high-risk behaviors in veterans with posttraumatic stress disorder.
AB  - The present study sought to identify posttraumatic stress disorder (PTSD)
      patients at high risk for negative behavioral outcomes (violence, suicide
      attempts, and substance use). The Mississippi Scale for Combat-Related PTSD, the
      Beck Depression Inventory, and demographic and behavioral data from 409 male
      combat veterans who completed a VA residential rehabilitation program for PTSD
      were analyzed using signal detection methods (receiver operating
      characteristics). A validation sample (N = 221) was then used to test
      interactions identified in the signal detection analyses. The best predictors of
      behaviors at follow-up were those same behaviors shortly before intake, followed
      by depressive and PTSD symptoms. However, for each of the models other than that
      for hard drug use, cutoffs determined at the symptom level did not lend
      themselves to replication. Recent high-risk behaviors, rather than patients'
      history, appear to be more predictive of high-risk behaviors postdischarge.

PMID- 15985842
TI  - Childhood sexual abuse and adult defensive functioning.
AB  - Differences in defensive functioning between those who reported a history of
      childhood sexual abuse (CSA) and those who did not was examined in a naturalistic
      treatment-seeking sample of adult outpatients (N = 67). Defensive functioning and
      childhood sexual abuse history were rated by clinicians and external raters
      utilizing the DSM-IV Defensive Functioning Scale and the Abuse Dimensions
      Inventory, respectively, based on information gathered as part of a larger
      therapeutic assessment. Individuals reporting a history of CSA were found to use
      more major image-distorting level defenses than the non-CSA group, and abuse
      severity was also related to greater use of major image-distorting level
      defenses. Those reporting a history of CSA relied more on defenses indicative of
      impairment in realistic perception of self and others. This defensive style
      likely contributes to the greater difficulties in interpersonal functioning and
      psychological problems in adulthood.

PMID- 15985843
TI  - Grandiose delusions: an experimental investigation of the delusion as defense.
AB  - Two distinct roles for emotion in the development of delusions have been
      outlined. Some authors argue that delusions defend against low self-esteem and
      negative emotion (the delusion-as-defense account). Other authors hypothesize
      that delusions are not a defense but are a direct reflection of emotion and
      associated processes (the emotion-consistent account). An empirical investigation
      was conducted of the delusion-as-defense account with reference to grandiose
      delusions. Twenty individuals with grandiose delusions and 21 individuals without
      mental illness were compared on overt and covert measures of self-esteem. No
      evidence for a discrepancy between overt and covert self-esteem in individuals
      with grandiose delusions was found. One potential interpretation of the results
      is that the tasks were not able to penetrate defensive processes. However, we
      argue that in this group, the grandiose delusions do not currently defend against
      low self-esteem. Instead, grandiose delusions may in part be direct exaggerations
      of the emotional state of individuals.

PMID- 15985844
TI  - Sleep complaints in panic disorder patients.
AB  - Patients with anxiety disorders often report difficulty sleeping. The present
      study assesses the prevalence of sleep complaints in panic disorder (PD)
      patients, compares them with sleep complaints in a normal population, and
      investigates the role of comorbid depression and nocturnal panic attacks in sleep
      complaints in the PD patients. Seventy PD patients and 70 healthy controls were
      asked about their subjective sleep characteristics by means of the Sleep-Wake
      Experience List, which assesses sleep/arousal complaints over a 24-hour period.
      Sixty-seven percent of the PD patients reported sleep complaints, compared with
      20% of the controls. Eighty-six percent of the depressed PD patients and 59% of
      the nondepressed had sleep difficulties; 77% of the PD patients with nocturnal
      panic attacks reported sleep complaints, versus 53% of the PD patients without
      nocturnal panic. It is concluded that PD patients demonstrate a higher prevalence
      of sleep complaints than normal controls; this can only partly be explained by
      comorbid depression, and cannot be explained by the presence of nocturnal panic
      attacks.

PMID- 15985849
TI  - Evidence-based medicine: an introduction for psychiatrists.
AB  - Evidence-based medicine (EBM) has been defined by Sackett as "the conscientious,
      explicit and judicious use of current best evidence in making decisions about the
      care of individual patients." Practicing evidence-based medicine requires the
      ability to apply a knowledge of medical informatics and clinical epidemiology to
      the treatment of individual patients. This article provides an introduction to
      the history, philosophy, and methods of evidence-based medicine for psychiatrists
      and other mental health professionals. The article focuses on a systematic
      approach to efficiently finding the best evidence to answer clinical questions.
      Particular emphasis is given to a method for critically appraising papers that
      emphasizes validity, importance, and clinical applicability. Resources for
      further learning are provided.

PMID- 15985850
TI  - Improving compliance in on-line, structured self-help programs: evaluation of an
      eating disorder prevention program.
AB  - Compliance rates from four iterations of Student Bodies, an 8-10 week computer
      assisted health education (CAHE) program for the prevention of eating disorders
      in college-aged women, were measured. Each iteration was modified with the hope
      of increasing participant compliance. Participants were 116 undergraduate women
      from two large West Coast universities who were randomly assigned to either the
      CAHE program or a wait-list group. Model 1 was delivered via CD-ROM, was
      anonymous, used an unstructured "grazing" approach, and participants received 10
      dollars. Model 2 was web-based, had recommended assignments with telephone
      reminders, and participants received 25 dollars. Model 3 used a more structured
      approach to assignments. Model 4 eliminated anonymity, added an academic
      component, used email reminders, and offered course units as an incentive.
      Compliance was defined as percentage of screens read per number of screens
      assigned (n = 27-33). In Model 1, compliance was self-reported at 53%. In Models
      2, 3, and 4, compliance, measured directly via computer logs, was 66%, 85%, and
      84%, respectively. A Mann-Whitney test showed that the increase in compliance
      between Models 2 and 3 and Models 2 and 4 was statistically significant (p <
      0.01). Compliance was significantly correlated with improvement on outcome.
      Suggestions for increasing compliance in other CAHE programs are offered.

PMID- 15985851
TI  - Behavioral and psychopharmacological treatment of the paraphilic and hypersexual
      disorders.
AB  - In this article, the second of a two-part series, the authors present information
      on the clinical assessment of individuals with paraphilias and hypersexual
      disorders. They review ethical considerations in the assessment and treatment of
      individuals with paraphilias. The role of interview and subjective and objective
      instruments in the assessment of individuals with paraphilias and hypersexual
      disorders is discussed. The authors discuss the use of penile plethysmography or
      phallometry, polygraphy, and viewing time assessments. Risk assessment of sexual
      offenders is reviewed. The authors then discuss behavioral, environmental, and
      psychopharmacological treatments for paraphilias and hypersexual disorders.
      Cognitive-behavioral therapy appears to be the most effective nonpharmacological
      strategy. The authors describe cognitive-behavioral techniques for decreasing
      and/or controlling sexual urges (e.g., satiation, covert sensitization, fading,
      cognitive restructuring, victim empathy therapy) as well as methods for enhancing
      appropriate sexual interest and arousal (e.g., social skills training,
      assertiveness skills training, sex education, couples therapy). The authors also
      discuss the role of relapse prevention therapy and 12-step programs, as well as
      other nonbiological therapies such as surveillance networks. The importance of
      providing appropriate treatment for comorbid conditions (e.g., depression,
      substance abuse or dependence) is stressed. The authors then review
      psychopharmacological treatments, including serotonin reuptake inhibitors (SRIs)
      and antiandrogens, in particular, the use of gonadotropin-releasing hormone
      (GNRH) agonists. SRIs have been studied in these disorders in an uncontrolled way
      and appear promising. Earlier antiandrogens (e.g., estrogen, progesterone, and
      cyproterone acetate) have demonstrated efficacy in the treatment of paraphilias.
      The newer GNRH agonists have the advantage over the earlier treatments of being
      available in long-acting depot formulations and having fewer side effects.
      Preliminary studies and case reports with these agents appear promising. Further
      study of both the SRIs and GNRH agonists in these disorders is needed. The
      article concludes with a treatment algorithm, in which the authors suggest
      beginning with less restrictive treatments (e.g., behavioral or verbal
      therapies), if possible, and moving to more restrictive alternatives (e.g.,
      biological therapies, institutionalization) as needed. A guide for clinicians and
      patients about where and how to find appropriate clinicians and treatment
      resources in the United States is provided.

PMID- 15985853
TI  - Drug approvals and withdrawals over the last 60 years.

PMID- 15985854
TI  - Evidence-based psychotherapy.

PMID- 15985852
TI  - SSRI efficacy-finding the right dose.
AB  - The selective serotonin reuptake inhibitors (SSRIs) are a class of effective,
      well-tolerated antidepressants. They have a number of benefits compared with the
      tricyclic antidepressants (TCAs) including improved safety in overdose, reduced
      side-effect burden, and uncomplicated dosing regimens. To avoid the potential for
      troublesome side effects with TCAs, doses should be gradually increased over
      several weeks. Dose titration can be associated with several drawbacks such as
      patients discontinuing therapy due to a prolonged time to therapeutic response,
      additional visits to a prescribing healthcare provider, or additional
      hospitalizations. In contrast, the SSRIs typically do not require dose titration
      since many patients find the initial dose effective. The ability to prescribe an
      initial optimum therapeutic dose while avoiding dose-related side effects is
      important in the treatment of major depression. With this in mind, the authors
      consider the recommended dose ranges for the five SSRIs: citalopram, fluoxetine,
      fluvoxamine, paroxetine, and sertraline.

PMID- 15985855
TI  - Evaluations in jails, prisons, and forensic facilities.

PMID- 15985856
TI  - ePocrates 4.0.

PMID- 15985857
TI  - Treatment resources for the paraphilic and hypersexual disorders.

PMID- 15985859
TI  - Patient and family support organization services should be included as part of
      treatment for the severely mentally ill.
AB  - Patient and family support organizations for Axis I disorders have grown
      exponentially and expanded their services over the past two decades. However,
      psychiatrists generally have not referred patients and families to these
      organizations. The goal of this paper is to change clinicians' behavior so that
      they more commonly include support organization services in treatment plans for
      patients and families. We performed a literature review focusing on the changing
      needs of patients and their families as they relate to mental health teams,
      changes in the family therapy field, and concerns of both healthcare providers
      and related organizations about referral. Abundant anecdotal evidence and some
      scientific data suggest that patients and families are satisfied with these
      support organizations and the services they provide. However, support
      organizations need clinician referrals in order for their services to be
      integrated into a multi-modal quality treatment plan to achieve full treatment
      efficacy.

PMID- 15985860
TI  - Substance abuse among patients with schizophrenia.
AB  - Substance use in the general population is a significant public health problem.
      Problems associated with substance use are aggravated by concomitant psychiatric
      illness, particularly schizophrenia and schizoaffective disorder. Although there
      is a general agreement on the need to address this problem, a wide range of
      opinions exists on exactly what is the best modality. In this article, we provide
      a brief overview of the etiology and consequences of substance use in individuals
      with schizophrenia, followed by a more detailed review of pharmacological and
      psychotherapeutic trends in the treatment of this population. Research studies
      indicate that, while some evidence supports the self-medication hypothesis,
      individuals with schizophrenia or schizoaffective disorder frequently use
      substances for the same reasons and in the same manner as the general population.
      In the pharmacotherapy section, we briefly discuss the rationale for current
      medication strategies, their efficacy, and directions for future research. This
      is followed by an assessment of current psychotherapeutic interventions, their
      limitations, and potential modifications to improve treatment outcome. The
      research literature suggests that integrated treatment and well-tailored
      interventions that take into account psychosocial factors and motivation offer
      the most promise for the future. More controlled trials are necessary to validate
      this hypothesis.

PMID- 15985861
TI  - Best clinical practice with ziprasidone: update after one year of experience.
AB  - This article presents clinical recommendations for using ziprasidone based on
      information from a year of post-marketing experience. The recommendations are
      based on the clinical literature, the package insert, presentations at recent
      meetings, data on file with the manufacturer, and the consensus of a panel of
      expert psychiatrists. The article provides updates on efficacy and safety data
      and gives recommendations for dosing and switching strategies. With regard to the
      QTc issue, there has not been any case of torsades de pointes reported in the
      more than 150,000 patients who have received ziprasidone since its approval.
      Ziprasidone is weight neutral and does not appear to cause increases in glucose
      or lipid levels or in insulin resistance. The panel generally recommends
      beginning with an initial dose of 80 mg/day (40 mg b.i.d.) rather than the 40
      mg/day dose recommended in the package insert. The ability to begin with a
      therapeutic dose and to titrate up rapidly is an advantage of ziprasidone,
      especially in treatment settings where admission time is short. In making an
      elective switch to ziprasidone, the panel recommends a variety of different
      switching strategies but stresses the importance of trying to maintain a
      therapeutic dose of one antipsychotic at all times.

PMID- 15985862
TI  - Is switching antipsychotics a good idea for me?

PMID- 15985863
TI  - Adults with attention-deficit/hyperactivity disorder: current concepts.
AB  - In recent years, the validity of attention-deficit/hyperactivity disorder (ADHD)
      in adulthood has gained acceptance among mental health researchers and
      clinicians. This article will outline the history of this process, provide our
      best understanding of the characteristics of ADHD in adulthood, review current
      guidelines and controversies in the assessment of adult ADHD, and summarize
      pharmacological and psychosocial treatment options. Despite the strides gained in
      understanding adult ADHD, the authors encourage more research on this population
      and caution that current conceptualizations of the disorder are based on a
      limited amount of empirically based knowledge.

PMID- 15985864
TI  - Physician perceptions of drug-drug interactions and how to avoid them.

PMID- 15985865
TI  - As long as ye both shall live.

PMID- 15985866
TI  - Forensic work and nonforensic clinicians-part I.

PMID- 15985867
TI  - Medem.com.

PMID- 15985868
TI  - Usefulness of the BASIS-32 in evaluating program level outcomes.
AB  - The Behavior and Symptom Identification Scale (BASIS-32) is a survey used to
      collect clients' reported perceptions of their symptoms and functioning. This
      article assesses the usefulness of the BASIS-32 for evaluating program outcomes
      in California's statewide performance outcome system for adults with serious
      mental illnesses. The authors found that, while the instrument could be useful at
      the clinical level, it did not work well when data were aggregated at the program
      or system level. Not only did clients drastically under-report their symptoms,
      but improvements over time, although statistically significant, were negligible
      and of little practical use for assessing system-level outcomes. In addition, the
      costs and logistical complexities associated with site licensing became
      increasingly difficult to justify when compared to obtaining similar information
      from other sources.

PMID- 15985870
TI  - The neurobiology of borderline personality disorder: the synergy of "nature and
      nurture".
AB  - The author reviews the current state of our knowledge concerning the neurobiology
      of borderline personality disorder (BPD). A converging body of scientific
      evidence indicates that patients with BPD suffer from impairments in the brain
      systems that regulate impulsivity, aggression, and affect. This article reviews
      data on the neurobiology of the symptoms of BPD, including emotional and
      behavioral dysregulation, identity disturbance, cognitive impairments, and
      interpersonal difficulties. The author first considers the evolutionary context
      in which BPD can develop to put the neurobiological findings in perspective, and
      then discusses the roles of both genetic inheritance and the environment in the
      development of BPD. The role of neurotransmitter systems in the development of
      impulsive-aggression and affective instability is reviewed. Possible
      neurobiological contributors to the identity disturbance seen in BPD are also
      described. The author then considers environmental contributions to BPD and
      discusses the synergy of nature and nurture in the development of BPD symptoms.
      Findings concerning the types of neurobiological impairments that can arise as a
      result of childhood neglect and abuse and other types of chronic severe stress
      and trauma are discussed. Finally, the author reviews studies of animal
      attachment models that suggest that types of maternal care can produce lifelong
      behavioral and physiological differences in offspring and that this effect is
      mediated through the regulation of gene expression. The author suggests that the
      large body of neuroscience research reviewed in this article suggests that, while
      patients with BPD may be born with innate genetic tendencies for impaired brain
      systems for regulating impulses and affect, the environment they find themselves
      born into may be critical in determining whether or not they develop the full
      blown syndrome of BPD.

PMID- 15985871
TI  - Routine HIV testing for the severely mentally ill: considerations and cautions.
AB  - The last few decades have brought major changes in both mental health laws and
      AIDS public health laws. The author first examines the impact of the HIV epidemic
      on those with severe and persistent mental illness. He then discusses how changes
      in public health laws have affected those infected with HIV and how changes in
      mental health laws have affected those with mental illness. People suffering from
      severe mental illness are increasingly being held legally responsible for their
      personal actions. At the same time, AIDS public health laws have begun to change
      so that those infected with HIV enjoy less legal protection and have more
      personal responsibility for transmitting the virus to others than in the recent
      past. The author then considers what impact the convergence of these legal
      changes is likely to have on the growing population of people with mental illness
      who are infected with HIV. The article concludes with some practical
      recommendations concerning HIV assessment and treatment in individuals with
      severe and persistent mental illness.

PMID- 15985872
TI  - Case studies in confidentiality.
AB  - Although a fundamental principle of psychiatric practice in general and
      psychotherapy in particular is that interactions and communications between
      clinician and patient are private, there are certain instances in which there is
      an affirmative obligation to break confidentiality, or in which such a breach is
      at least legally (if not ethically) permitted. The author examines the various
      situations in which a psychiatrist's obligation to maintain confidentiality is
      modified or even completely overridden by some other competing clinical, legal,
      or ethical principle or obligation. He reviews the duty to protect third parties
      (Tarasoff warnings), situations in which a psychiatrist's loyalties are divided
      between the patient and some other entity, person, or principle (dual agency
      issues), the release of information in emergencies, and the reporting of abuse.
      He also discusses the circle of confidentiality and which individuals are deemed
      to be inside and outside that circle. Guidelines for the use of clinical material
      in presentations and publications are reviewed. The author also considers how
      psychiatrists should deal with knowledge of past criminal behavior that they may
      obtain during the course of treatment. Finally, the author discusses the need to
      carefully document the rationale for whatever course of action is taken.

PMID- 15985873
TI  - Executive control function in psychiatric and medical illness.
AB  - Executive Control Function (ECF) is the ability to plan, sequence, and monitor
      one's behavior in order to accomplish a given goal while simultaneously
      exercising cognitive flexibility to adapt to changing task requirements. Multiple
      studies demonstrate that ECF predicts functional outcome, level of care required,
      and work potential for both well and ill populations. However, clinicians often
      do not routinely assess ECF during mental status evaluations because of the
      perceived lack of practical bedside tests. This review article discusses the
      major neuropsychological measures used to probe for impairment, with special
      emphasis on those that are easily administered at the patient's bedside. The
      current literature on executive dysfunction in psychiatric and medical illness is
      reviewed. The neuroanatomy and neurochemistry of ECF is also reviewed, with
      emphasis on structural dysfunction in specific illnesses. Finally, various
      treatment options, both pharmacological and psychotherapeutic, are discussed.

PMID- 15985874
TI  - The overlap of DSM-IV syndromes: potential implications for the practice of
      polypsychopharmacology, psychiatric drug development, and the human genome
      project.

PMID- 15985875
TI  - Psychodynamics in the E.R.

PMID- 15985876
TI  - Forensic work and nonforensic clinicians part II: reports and depositions.

PMID- 15985878
TI  - The "softer" end of the bipolar spectrum.
AB  - The prevalence and diversity of bipolar disorder may be under appreciated. Recent
      data suggest that when clinicians look beyond strict DSM-IV criteria for bipolar
      disorder, we find that as many as 5%-7% of the general public may suffer from
      some form of "bipolar spectrum disorder." At the same time, the comorbidity
      between bipolar disorder and other psychiatric conditions may create
      understandable confusion in diagnosis and treatment. Recognition of bipolar
      depression and the "soft end" of the bipolar spectrum demands not only the
      identification of the hallmarks of bipolarity, but a heightened awareness of the
      problems of missed diagnosis and inappropriate treatment. By attending to some
      key historical and clinical clues, the psychiatrist is more likely to detect
      bipolar spectrum disorder and provide appropriate treatment for it.

PMID- 15985879
TI  - Psychiatric disturbances in children of parents with bipolar disorder.
AB  - The early symptoms of bipolar disorder in children and adolescents are often
      qualitatively different from the classic symptoms of mania and depression that
      present in adults, complicating the diagnosis of the disorder in younger
      populations. The focus of this article is the evaluation and treatment of
      children with bipolar parents who begin to develop behavioral and other
      psychiatric problems. The authors first review the current criteria available for
      diagnosing bipolar disorder in children. They consider issues related to how the
      DSM-IV criteria have been applied in this population, in particular the increase
      in the number of children diagnosed with bipolar disorder as a result of the
      decision to allow a "manic" episode to be diagnosed in the absence of expansive
      or elated mood. The practice parameters for the diagnosis and treatment of
      bipolar disorder in children and adolescents developed by the American Academy of
      Child and Adolescent Psychiatry are also discussed. The literature concerning
      children of parents with bipolar disorder is reviewed and indicates that these
      children are at increased risk for a wide range of psychiatric disorders,
      including bipolar disorders, other affective disorders, disruptive behavior
      disorders, and other psychiatric illnesses. The authors then review what is known
      about treatment for the early symptoms of bipolar disorder in this population and
      discuss the utility of mood stabilizers. The authors then discuss the role
      genomic screening may play in the future in identifying children at the highest
      risk for developing bipolar disorder. The article concludes with a summary of
      several endophenotypic expressions of bipolar disorder that have been described
      in children of parents with bipolar disorder.

PMID- 15985880
TI  - Managing treatment-resistant schizophrenia: evidence from randomized clinical
      trials.
AB  - Clozapine was the first antipsychotic medication to be approved for the
      indication of treatment-refractory schizophrenia. This followed rigorous testing
      in patients who retrospectively and prospectively failed treatment trials of
      relatively high doses of conventional antipsychotics. In the past decade, other
      atypical antipsychotics have been approved, but they have not been designated
      specifically for patients with a history of prior poor treatment response. Better
      tolerated than clozapine, these new agents have been used with varying success in
      patients who would have otherwise received clozapine. Up until very recently
      there has not been a head-to-head controlled clinical trial comparing the two
      most commonly used atypical antipsychotics, risperidone and olanzapine, with
      clozapine in patients considered to have a suboptimal response to typical
      antipsychotics. This review summarizes the current advances made in the
      pharmacological management of these patients by examining recently published
      randomized controlled clinical trials that have measured psychopathology and
      cognition.

PMID- 15985881
TI  - Personality dynamics of intimate abusiveness.
AB  - A new theory is proposed to account for individual differences in the tendency to
      be abusive, assaultive, or homicidal in intimate relationships. The focus of this
      theory is on men whose abuse is specific to intimate relationships and is
      manifested through cyclical mood swings. This group, which appears to comprise
      about 40% of all men who present for treatment for wife assault, appears to have
      a borderline personality structure. For these men, abusiveness is triggered by
      internal mood states rather than by external events. Several studies are cited
      indicating that intimate attachment generates rage in wife assaulters. The
      origins of this attachment-rage are traced to early development. This template
      generates a complex of perceptions (attributions and projections) and behaviors
      (abusiveness) specific to intimate relationships. A personality profile of
      intimately abusive males has been strongly related to intimate partners' reports
      of psychological abusiveness in several samples of males, including physically
      assaultive males, non-violent controls, clinical outpatients, college students,
      and gay males.

PMID- 15985883
TI  - Fatal drug-drug interaction as a differential consideration in apparent suicides.

PMID- 15985884
TI  - Neurodynamics: a practitioner's view.

PMID- 15985885
TI  - ICANotes (Clinician) v.4.13.2 for Windows.

PMID- 15985886
TI  - Forensic work and nonforensic clinicians part III: testifying in court.

PMID- 15985887
TI  - The international language of psychiatry.

PMID- 15985888
TI  - The PACE Clinic: identification and management of young people at "ultra" high
      risk of psychosis.
AB  - Over the past decade, both clinical and research interest in the early stages of
      psychotic disorders has grown. This has been associated with research suggesting
      that early intervention in these disorders may limit their impact on the life of
      the affected individual and his or her family. It has also been recognized that
      the biological and psychological changes underpinning the development of
      psychotic disorders may already be active in the prepsychotic or prodromal phase.
      It has been suggested that efforts to prevent psychotic disorders should be
      focused on this phase of emerging illness. In this article, the authors review
      work conducted at the PACE Clinic in Melbourne, Australia since 1994. This
      clinical research program was established to develop strategies for identifying
      young people at high risk for developing a psychotic disorder within a short
      period. The program has also investigated biological and psychological processes
      thought to underlie the development of psychosis and evaluated potential
      preventive interventions.

PMID- 15985889
TI  - Meta-analysis of left prefrontal repetitive transcranial magnetic stimulation
      (rTMS) to treat depression.
AB  - INTRODUCTION: Depression is a common and severe disorder for which new treatments
      are needed. Repetitive transcranial magnetic stimulation (rTMS) is a promising
      new treatment. The purpose of this meta-analysis was to determine whether the
      literature supports the use of left prefrontal rTMS as a treatment option for
      depression. METHODS: The literature was searched for randomized sham-controlled
      trials of left prefrontal rTMS to treat depression using PsycINFO, MEDLINE, and
      CURRENT CONTENTS as well as two previous meta-analyses of rTMS. Using MetaWin, a
      Hedges' d effect size and nonparametric variances were calculated in order to
      determine a cumulative effect size. Tests for heterogeneity and publication bias
      were also calculated. RESULTS: Twelve of fourteen studies (n = 230) were suitable
      for analysis. The summary analysis revealed a cumulative effect size of 0.53 (95%
      CI 0.24-0.82). The test for heterogeneity was not significant (Qtotal = 10.65, df
      = 11, Prob {chi} = 0.47). The fail-safe result using the Rosenthal's method (55.1
      non-significant studies) and the Orwin's method (20.0 non-significant studies)
      revealed that 20 to 55 studies would have to be unavailable in order to change
      the cumulative effect to a non-significant result. DISCUSSION: The meta-analysis
      supports the hypothesis that left prefrontal rTMS is an acute antidepressant
      treatment with statistically significant effect sizes and measurable clinical
      improvement.

PMID- 15985890
TI  - Clinical features of pedophilia and implications for treatment.
AB  - The authors discuss the diagnostic criteria for pedophilia and review the
      literature on its clinical features, including data on prevalence, gender, age of
      onset, number of victims, frequency and type of acts, violence, impulsivity, and
      insight. Findings concerning the characteristics of victims (e.g., sex, age,
      relationship to the pedophile) and research on pedophilic subtypes-exclusive
      versus nonexclusive; incestuous versus nonincestuous; heterosexual, homosexual,
      or bisexual-are reviewed. Studies have shown that pedophiles may share many
      psychiatric features beyond deviant sexual desire, including high rates of
      comorbid axis I disorders (affective disorders, substance use disorders, impulse
      control disorders, other paraphilias) as well as severe axis II psychopathology
      (especially antisocial and Cluster C personality disorders). The authors present
      several possible etiological models for pedophilia and conclude that further
      research is needed concerning the etiological role of a childhood history of
      sexual abuse as well as the underlying neurobiology of deviant sexual arousal and
      decreased erotic differentiation. Finally, findings concerning pharmacological
      and cognitive-behavioral treatments for pedophilia are briefly reviewed.
      Recidivism, drop-out, and noncompliance are significant problems in the treatment
      of pedophilia. The authors review predictors of treatment outcome and conclude
      that pedophilia is extremely difficult to treat and that effective treatment
      needs to be intensive, long-term, and comprehensive, possibly with lifetime
      follow-up.

PMID- 15985891
TI  - Ethics in psychiatric practice: essential ethics skills, informed consent, the
      therapeutic relationship, and confidentiality.
AB  - Psychiatrists routinely encounter ethical complexities in caring for patients
      with mental illness, and they are held to the highest levels of accountability in
      their ethical practices. In this article, the authors first outline skills that
      are essential to ethical psychiatric practice. They then articulate three domains
      of clinical and ethical practice that represent the foundation of clinical care
      for people with mental illness: informed consent, the therapeutic relationship,
      and confidentiality. Key concepts concerning these domains are presented and
      relevant empirical evidence concerning each domain is reviewed. An understanding
      of these clinical and ethical practices will help psychiatrists serve patients
      with mental illness in their everyday clinical activities in a manner that is
      respectful, engenders trust, and ultimately fosters optimal clinical care.

PMID- 15985892
TI  - Clinical pharmacology case conference: a suicide attempt?

PMID- 15985893
TI  - A treatment consent form.

PMID- 15985894
TI  - APA Online CME Practice Guideline for the Treatment of Patients with Major
      Depressive Disorder.

PMID- 15985895
TI  - Sexual predator evaluations and commitments.

PMID- 15985896
TI  - Patient satisfaction among combat veterans receiving specialty PTSD treatment.
AB  - BACKGROUND: Despite the difficulties with successfully developing effective
      treatments for posttraumatic stress disorder (PTSD), very little research has
      been conducted on veterans' perceptions of satisfaction with the treatments they
      receive through the VA. OBJECTIVE: Our objective was to evaluate combat veterans'
      satisfaction with Veterans Affairs (VA) services and to evaluate the reliability
      and preliminary validity of a measure of patient satisfaction, the Charleston
      Psychiatric Outpatient Satisfaction Scale-VA PTSD Version, which was originally
      designed for general psychiatric outpatients. METHOD: Fifty-one combat veterans
      currently receiving specialty mental health care at a VA outpatient PTSD clinic
      were asked to complete two instruments designed to assess their satisfaction with
      services provided within the VA mental health and primary care clinics. RESULTS:
      Data show that the reliability (alpha = 0.96 and 0.95) and validity of these two
      measures of patient satisfaction were good and indicate that veterans receiving
      specialty mental health care for PTSD rate their mental health and primary care
      quite positively. CONCLUSIONS: These results provide preliminary support for the
      internal reliability and convergent validity of a novel measure of patient
      satisfaction for use with combat veterans suffering from PTSD and treated within
      a VA hospital specialty mental health clinic; the results also support the
      satisfaction of these patients with mental health and primary care services
      received through the VA.

PMID- 15985899
TI  - Is biology destiny? Is it all in our genes?
AB  - The completion of the working draft of the human genome in 2001 is an important
      milestone in achieving greater understanding of the role of genetics in health
      and disease. This very important technological achievement holds both promise and
      peril for the theory and practice of medicine. The author discusses how the
      information in the genome, coupled with insights into the interactions of gene
      and environment, may revolutionize clinical practice and eventually make it
      possible to tailor diagnosis and treatment to the allelic and experiential nature
      of the individual patient. He also points out the dangers of leaping from gene
      discovery to premature diagnosis and unproven interventions that may endanger
      patients and gives several examples of such occurrences. What is known about the
      relationship between gene and phenotype is reviewed and examples of the different
      phenotypes that may arise with identical genomes are presented to illustrate how
      environment influences gene expression, both in humans and other species.
      Finally, the author considers the challenge in conveying newly gained knowledge
      of genetic risk in ways that will benefit rather than harm patients.

PMID- 15985900
TI  - In their own voices: families in crisis: a focus group study of families of
      persons with serious mental illness.
AB  - This qualitative study employs a focus group methodology to learn more about the
      needs of family caregivers of persons with serious mental illness during crisis.
      Changes in psychiatric status or residential placement are always stressful
      times, for both patients and their families. But no experience has as profound an
      effect on families as the "first-break." While intuitively this appears to be an
      ideal time for intervention, few families report that they obtain the supports
      they need during the early years of their relative's illness. Based on dialogues
      with families, two sets of recommendations are presented to improve the timely
      provision of services and supports: one set for families and the other for mental
      health policymakers.

PMID- 15985901
TI  - How siblings of those with severe mental illness perceive services and support.
AB  - This study examines the complex and varied effects associated with having a
      brother or sister with a severe and persistent mental illness (SPMI) on the lives
      of adult siblings without chronic disability. Through five focus group
      interviews, 19 participants were asked to describe the impact that having a
      brother or sister with mental illness had on their lives. Codes and categories
      derived from the text of the transcribed interviews were grouped into broad
      themes. The respondents described the manifestations and challenges of contending
      with the SPMI of an adult sibling. They focused on gaps in services and
      communication with mental health providers, particularly with regard to timing of
      interventions and identifying readiness for treatment, as well as their own
      mental health needs. The article concludes with a discussion of the increased
      need for exchange of information and clarity of communication among family
      members and providers, following best practice guidelines that are well
      documented but not well implemented.

PMID- 15985902
TI  - Evaluating awareness of New York's Assisted Outpatient Treatment Law among adult
      siblings of persons with mental illness.
AB  - This study examined knowledge of New York's Assisted Outpatient Treatment law,
      enacted November 1999, among adult siblings of persons with mental illness.
      Mailed survey responses collected between April, 2000 and September, 2001 from
      100 siblings residing in New York State were reviewed. Only 48% acknowledged
      familiarity with the law. Possessing higher education, reading about mental
      illness more often, planning to occupy future caregiving roles, maintaining
      membership in a support group, and reporting that their siblings experienced more
      difficulties with treatment compliance were associated with a familiarity with
      the law. Among those aware of the law, two thirds incorrectly believed
      eligibility for a court order was contingent on a history of violent behavior.
      Low rates of general awareness and knowledge of the law highlight the need for
      further community education.

PMID- 15985903
TI  - Polypharmacy in a patient with refractory major depression: part I: the case.

PMID- 15985904
TI  - Subtleties of self.

PMID- 15985905
TI  - Ethics and forensic work.

PMID- 15985906
TI  - Why did John Nash stop his medication?

PMID- 15985907
TI  - APA online CME: buprenorphine for office-based treatment of opiate dependent
      patients.

PMID- 15985909
TI  - Why do patients stop their antipsychotic medications? A guide for families and
      friends.

PMID- 15985908
TI  - From King George to neuroglobin: the psychiatric aspects of acute intermittent
      porphyria.
AB  - The porphyrias are a heterogeneous group of inherited deficiencies in the heme
      biosynthetic pathway. Acute intermittent porphyria is both the most prevalent and
      most severe form of this illness. Psychiatric symptoms are part of the classic
      presentation of this disorder, and psychiatric patients have a higher rate of
      porphyria than the general population. Despite this, clinicians often fail to
      consider this diagnosis in the differential for recalcitrant psychosis or
      depression. Many patients are asymptomatic until exposed to certain medications,
      liver damage, or hormonal changes. Diagnosis requires a high index of suspicion
      and a thorough history, physical examination, and laboratory evaluation. The
      author reviews historical aspects, diagnostic features, and optimal treatment of
      acute intermittent porphyria, considers possible etiologies of its psychiatric
      symptoms, and provides two case histories as examples.

PMID- 15985910
TI  - Treatment or safety management?

PMID- 15985911
TI  - Usefulness of the BASIS-32 in evaluating program level outcomes.

PMID- 15985912
TI  - Elements of successful restraint and seclusion reduction programs and their
      application in a large, urban, state psychiatric hospital.
AB  - In recent years, there has been a strong desire on the part of inpatient
      psychiatric programs to reduce the use of seclusion and mechanical restraint.
      There is a consensus among those who have published descriptions of successfully
      implemented restraint and seclusion reduction programs that the essential
      elements of such programs are high level administrative endorsement,
      participation by recipients of mental health services, culture change, training,
      data analysis, and individualized treatment. This article describes these
      elements and their application in a successful restraint reduction program at
      Creedmoor Psychiatric Center, a large, urban, state-operated psychiatric hospital
      that reduced its combined restraint and seclusion rate by 67% over a period of 2
      years.

PMID- 15985913
TI  - Treatment of behavioral emergencies: a summary of the expert consensus
      guidelines.
AB  - OBJECTIVES: Behavioral emergencies are a common and serious problem for
      consumers, their communities, and the healthcare settings on which they rely, but
      there is little research to guide provider responses to this challenge. Key
      constructs such as agitation have not been adequately operationalized so that the
      criteria defining a behavioral emergency are vague. A significant number of
      deaths of patients in restraint has focused government and regulators on these
      issues, but a consensus about key elements in the management of behavioral
      emergencies has not yet been articulated by the provider community. The authors
      assembled a panel of 50 experts to define the following elements: the threshold
      for emergency interventions, the scope of assessment for varying levels of
      urgency and cooperation, guiding principles in selecting interventions, and
      appropriate physical and medication strategies at different levels of diagnostic
      confidence and for a variety of etiologies and complicating conditions. METHOD: A
      written survey with 808 decision points was completed by 50 experts. A modified
      version of the RAND Corporation 9-point scale for rating appropriateness of
      medical decisions was used to score options. Consensus on each option was defined
      as a non-random distribution of scores by chi-square "goodness-of-fit" test. We
      assigned a categorical rank (first line/preferred choice, second line/ alternate
      choice, third line/usually inappropriate) to each option based on the 95%
      confidence interval around the mean rating. Guideline tables were constructed
      describing the preferred strategies in key clinical situations. RESULTS: The
      expert panel reached consensus on 83% of the options. The relative
      appropriateness of emergency interventions was ascertained for a continuum of
      behaviors. When asked about the frequency with which emergency interventions
      (parenteral medication, restraint, seclusion) were required in their services,
      47% of the experts reported that such interventions were necessary for 1%-5% of
      patients seen in their services and 32% for 6%-20%. In general, the consensus of
      this panel lends support to many elements of recent regulations from the Health
      Care Financing Administration (now the Centers for Medicare and Medicaid
      Services), including the timing of clinician assessment and reassessment and the
      intensity of nursing care. However, the panel did not endorse the concept of
      "chemical restraint," instead favoring the idea that medications are treatments
      for target behaviors in behavioral emergencies even when the causes of these
      behaviors are not well understood. Control of aggressive behavior emerged as the
      highest priority during the emergency; however, preserving the physician-patient
      relationship was rated a close second and became the top priority in the long
      term. Oral medications, particularly concentrates, were clearly preferred if it
      is possible to use them. Benzodiazepines alone were top rated in 6 of 12
      situations. High-potency conventional antipsychotics used alone never received
      higher ratings than benzodiazepines used alone. A combination of a benzodiazepine
      and an antipsychotic was preferred for patients with suspected schizophrenia,
      mania, or psychotic depression. There was equal support for high-potency
      conventional or atypical antipsychotics (particularly liquids) in oral
      combinations with benzodiazepines. Droperidol emerged in fourth place in some
      situations requiring an injection. CONCLUSIONS: To evaluate many of the treatment
      options in this survey, the experts had to extrapolate beyond controlled data.
      Within the limits of expert opinion and with the expectation that future research
      data will take precedence, these guidelines provide some direction for addressing
      common clinical dilemmas in the management of psychiatric emergencies and can be
      used to inform clinicians in acute care settings regarding the relative merits of
      various strategies.

PMID- 15985914
TI  - What do consumers say they want and need during a psychiatric emergency?
AB  - Behavioral emergencies are a common and serious problem for consumers, their
      families and communities, and the healthcare providers on whom they rely for
      help. In recent years, serious concerns about the management of behavioral and
      psychiatric emergencies-in particular, the misapplication and overuse of physical
      and chemical restraints and seclusion-have become a focus of attention for mental
      health professionals and policy makers as well as for the lay public, the media,
      and patient advocacy organizations. Policy leaders and clinicians are searching
      for ways to balance the rights of consumers with considerations of safety and
      good care in an area in which it is difficult to conduct research. A survey of
      mental health professionals who are experts on the treatment of psychiatric and
      behavioral emergencies identified consumer input and collaboration between
      patient and clinician whenever possible as being extremely important in achieving
      the best short-term and particularly the best long-term outcomes for patients.
      The survey of consumer perspectives described in this article was undertaken in
      response to the need to better understand consumer experiences and preferences.
      The authors describe four emergency services forums conducted in 2002, which
      involved a total of 59 consumers. Each forum involved a written consumer survey
      as well as a workshop to develop and prioritize recommendations for improving
      psychiatric emergency care. The authors present the results of the consumer
      survey and summarize the top recommendations from the workshops. In both the
      survey and the workshops, the consumers repeatedly stressed the importance of
      having staff treat them with respect, talk to them, listen to them, and involve
      them in treatment decisions. There were a number of important areas of agreement
      between the recommendations of the consumer panel and those of the experts in
      emergency psychiatry surveyed for the Expert Consensus Guidelines on the
      Treatment of Behavioral Emergencies. These include the desirability of verbal
      interventions, the use of a collaborative approach, and the use of oral
      medications guided by the individual consumer's problems, medication experiences,
      and preferences. The majority of the consumer panel reported adverse experiences
      with general hospital emergency rooms and, in fact, called for the development of
      specialized psychiatric emergency services such as those recommended in the
      Expert Consensus Guidelines. One-fifth of the consumer panel attributed their
      emergency contact to lack of access to more routine mental health care. The
      consumers clearly do not reject medications categorically. Almost half indicated
      that they wanted medications and a similar number indicated benefit from
      medications, although many complained of forced administration and unwanted side
      effects. The consumer panel preferred benzodiazepines and ranked haloperidol as a
      least preferred option. Among their key recommendations for improving psychiatric
      emergency care, the consumer panel stressed the development of alternatives to
      traditional emergency room services, the increased use of advance directives,
      more comfortable physical environments for waiting and treatment, increased use
      of peer support services, improved training of emergency staff to foster a more
      humanistic and person-centered approach, increased collaboration between
      practitioners and patients, and improved discharge planning and post-discharge
      follow-up. The implications of these findings for improving psychiatric emergency
      care are considered.

PMID- 15985915
TI  - The controversy over "chemical restraint" in acute care psychiatry.
AB  - In many healthcare settings, medications are considered a less invasive
      alternative to the use of physical restraint for agitated patients experiencing a
      behavioral crisis, a practice that is often referred to as "chemical restraint."
      However, recent federal regulations appear to equate chemical and physical
      restraint and to characterize both as extraordinary practices that should not be
      undertaken lightly. Although many clinicians consider the term "chemical
      restraint" pejorative, since it does not reflect the possibility that forced
      medication may be clinically necessary and have a beneficial effect, the term is
      embedded in recent regulatory language. The author first reviews the controversy
      over the concept of chemical restraint as it has developed in the mental health
      literature and regulatory policy. As yet there is no consensus among clinicians
      or policy makers whether such use of medications is a form of coercion or a form
      of patient-focused intensive care. The author then discusses precipitants of
      emergency care and clinical factors and situations that may lead to the use of
      medications in a way that might be considered chemical restraint. Such factors
      include clinical and demographic characteristics of patients, institutional
      characteristics, and staff perception and attitudes. In the final section of the
      article, the author reviews the recommendations concerning the emergency use of
      medications given in the Expert Consensus Guidelines on the Treatment of
      Behavioral Emergencies and discusses treatment developments that have occurred
      since the time of the survey on which those guidelines were based.

PMID- 15985916
TI  - Polypharmacy in a case of refractory major depression: part II: implications for
      clinical management.

PMID- 15985917
TI  - In sickness and in health.

PMID- 15985918
TI  - Risk assessment, prediction, and foreseeability.

PMID- 15985919
TI  - Two cases of brief psychotic disorder related to media coverage of the September
      11, 2001 events.
AB  - To our knowledge new-onset psychotic symptoms have not been reported in
      connection with the September 11, 2001 terrorist attacks on the World Trade
      Center and the Pentagon. We describe two cases of brief psychotic disorder in
      adults who experienced the terrorist attacks from afar through television
      coverage. The patients were brought in for assessment to a medical center in the
      northeastern United States approximately 2 weeks after the attacks on September
      11. We discuss the role of television coverage of stressful events in the
      induction of psychotic symptoms.

PMID- 15985920
TI  - Psychiatry at the table.

PMID- 15985922
TI  - Psychiatric disorders in individuals with pervasive developmental disorder.
AB  - Pervasive developmental disorders (PDD) refer to the group of heterogeneous
      conditions that make up a continuum or spectrum of autistic disorders and share a
      core triad of impairments consisting of qualitative disturbances in social
      interaction and verbal and nonverbal communication and imagination. It has long
      been believed that the prevalence of autism was 2-4 per 10,000 children. However,
      studies using broader definitions of autistic disorder have suggested that the
      prevalence of autism spectrum disorder may be as high as 90 per 10,000 and that a
      greater proportion of individuals with PDD have intellectual levels above 70.
      Clinicians and researchers have commented on the apparent increase in prevalence
      of the disorder and have offered a number of explanations, including better
      recognition and diagnosis of the autism spectrum of disorders and a real increase
      in the disturbance. It is being increasingly recognized that individuals with PDD
      are at risk for a wide array of psychiatric disturbances, including affective
      disorder, anxiety disorders, schizophrenia-like psychosis, aggression, antisocial
      behavior, and Tourette's disorder (TD). Evidence indicates that PDD is
      significantly related to the comorbid psychiatric disorders and TD. Because PDD
      is not rare, individuals with autism spectrum disorder may represent significant
      subgroups of severely emotionally disturbed patients referred for psychiatric
      treatment. Because of lack of awareness that the clinical manifestations of PDD
      are heterogeneous and often mild and that comorbid psychiatric disturbances may
      obscure the symptoms of the developmental disorder, the diagnosis of PDD may be
      missed. Implications for practicing clinicians are discussed.

PMID- 15985921
TI  - Comprehensive review of hepatitis C for psychiatrists: risks, screening,
      diagnosis, treatment, and interferon-based therapy complications.
AB  - Hepatitis C is an RNA virus responsible for chronic infection in at least 4
      million Americans. Patients are often unaware that they have contracted the virus
      until the appearance of long-term consequences of the infection, primarily
      cirrhosis and hepatocellular carcinoma. Many patients with hepatitis C have
      comorbid psychiatric and/or substance abuse disorders. Treatments for hepatitis C
      infection are based on interferon-alfa therapy and have shown increasing
      effectiveness in recent years; however, interferon-alfa therapy also poses
      significant risks for physical and neuropsychiatric side effects. Since
      psychiatrists often serve as primary caregivers for patients who are at higher
      risk for hepatitis C infection, knowledge about the diagnosis, prognosis, and
      treatment of this disease is needed. In the first half of this article, the
      authors review the epidemiology, transmission, pathophysiology and disease course
      of hepatitis C, as well as the neuropsychiatric complications of hepatitis C
      infection. They also discuss the incidence of comorbid psychiatric disorders in
      patients with hepatitis C infection and consider the impact of the infection on
      patients' quality of life. The authors then provide an overview of the clinical
      management of HCV infection, including screening procedures, decision-making
      about treatment, available treatments (interferon-alfa, pegylated interferon
      alpha, combination therapy with interferon and ribavirin) and their side effects
      and potential drug-drug interactions, and prediction of treatment response. The
      authors then discuss management of the neuropsychiatric complications of
      treatment with interferon-alpha and ribavirin, including depression, mania and
      psychosis, and cognitive and neurological complications. The final section of the
      article focuses on special issues related to the treatment of hepatitis C
      infection in patients with substance abuse or dependence and/or other comorbid
      psychiatric illness.

PMID- 15985923
TI  - Impact of trauma on children.
AB  - Millions of children are affected by physical and sexual abuse, natural and
      technological disasters, transportation accidents, invasive medical procedures,
      exposure to community violence, violence in the home, assault, and terrorism.
      Unfortunately, the emotional impact of exposure to trauma on children is often
      unappreciated and therefore untreated, and yet the impact of exposures to
      disaster and violence is profound and long-lasting. This article first briefly
      discusses the epidemiology of trauma in children, and then reviews the
      psychiatric and neurodevelopmental impact of trauma on children as well as the
      effects of trauma on children's emotional development. Trauma in children can
      lead to the development of posttraumatic stress disorder as well as to a variety
      of other psychiatric disorders, including depression, generalized anxiety
      disorder, panic attacks, borderline personality disorder, and substance abuse in
      adult survivors of trauma. Research has found that early exposure to stress and
      trauma causes physical effects on neurodevelopment which may lead to changes in
      the individual's long-term response to stress and vulnerability to psychiatric
      disorders. Exposure to trauma also affects children's ability to regulate,
      identify, and express emotions, and may have a negative effect on the
      individual's core identity and ability to relate to others. The authors also
      discuss what has been learned, based on recent experiences such as the World
      Trade Center catastrophe, about the role of television viewing in increasing the
      effects of traumatic events. The last section of the article provides guidance
      concerning the identification and clinical treatment of children and adolescents
      who are having emotional problems as a result of exposure to trauma.

PMID- 15985925
TI  - Reproducibility of the in vivo effect of the selective serotonin reuptake
      inhibitors on the in vivo function of cytochrome P450 2D6: an update (part I).

PMID- 15985924
TI  - Abortion and psychiatric practice.
AB  - The subject of abortion is fraught with politics, emotions, and misinformation. A
      widespread practice reaching far back in history, abortion is again in the news.
      Psychiatry sits at the intersection of the religious, ethical, psychological,
      sociological, medical, and legal facets of the abortion issue. Although the
      religions that forbid abortion are more prominent in the media, many religions
      have more liberal approaches. While the basic right to abortion has been upheld
      by the U.S. Supreme Court, several limitations have been permitted, including
      parental notification or consent (with the possibility of judicial bypass) for
      minors, waiting periods, and mandatory provision of certain, sometimes biased,
      information. Before the Roe v. Wade decision legalizing abortion in 1973, many
      women were maimed or killed by illegal abortions, and psychiatrists were
      sometimes asked to certify that abortions were justified on psychiatric grounds.
      Currently, there are active attempts to convince the public and women considering
      abortion that abortion frequently has negative psychiatric consequences. This
      assertion is not borne out by the literature: the vast majority of women tolerate
      abortion without psychiatric sequelae. The psychiatric outcome of abortion is
      best when patients are able to make autonomous, supported decisions.
      Psychiatrists need to know the medical and psychiatric facts about abortion.
      Psychiatrists can then help patients prevent unwanted pregnancies, make informed
      decisions consonant with their own values and circumstances when they become
      pregnant, and find appropriate social and medical resources whatever their
      decisions may be.

PMID- 15985926
TI  - Tomography of the mind.

PMID- 15985927
TI  - Why nonforensic clinicians should decline forensic referrals.

PMID- 15985928
TI  - A severe case of clonidine dependence and withdrawal.

PMID- 15985929
TI  - Two models of psychiatric rehabilitation: a need for clarity and integration.
AB  - Two distinct models are identifiable in the processes of psychiatric
      rehabilitation: treatment and training. The treatment model, which also can be
      presented as the "medical model," approaches the issues on the basis of defect
      which needs to be diagnosed and rectified. On the other hand, the training model,
      which can also be referred to as the "educational model," approaches the
      situation from the perspective of recognizing what strengths or abilities the
      individual may have which can be brought to bear constructively, and how to
      orchestrate that process. These two models involve different perspectives and
      different processes, and the model which is chosen affects the relationship of
      the clinician to the consumer. In the practical clinical situation, a thoughtful
      amalgam of these two orientations is called for in order best to serve the
      recipient. But clinicians nevertheless benefit from remaining aware of the two
      models involved and their attendant assumptions and modes of action, so that
      inconsistencies are minimized while the most effective and integrated services
      are provided. Administrators, payers, and researchers will similarly benefit from
      an understanding of the potential benefits of each of these two approaches to
      intervention.

PMID- 15985930
TI  - Screening and prevention.

PMID- 15985931
TI  - When do antidepressants worsen the course of bipolar disorder?
AB  - Bipolar disorder may be more prevalent than previously believed. Because a
      substantial number of patients with bipolar disorder present with an index
      depressive episode, it is likely that many are misdiagnosed with unipolar major
      depression. Even if a correct diagnosis is made, depressive symptoms in bipolar
      disorder are notoriously difficult to treat. Patients are often treated with
      antidepressants, which, if used improperly, are known to induce mania and provoke
      rapid cycling. This article explores diagnostic conundrums in bipolar depression
      and their possible solutions, based on current research evidence. It also
      elucidates current evidence regarding the risks and benefits associated with
      antidepressant use and evaluates alternative treatment regimens for the depressed
      bipolar population, including the use of traditional mood stabilizers such as
      lithium, novel anticonvulsants such as lamotrigine, and atypical antipsychotics.

PMID- 15985932
TI  - Treatment of alcohol use disorders in adolescents.
AB  - The treatment of alcohol use disorders (AUDs) in adolescents is a very important
      issue in the field of substance use disorders; however, it is a complex and
      understudied area in which there are limited data concerning evidence-based
      treatment. The authors first briefly review the epidemiology of AUDs in
      adolescents, describe existing guidelines for the treatment of such disorders in
      adolescent patients, and consider differences between AUDs as they present in
      adolescents and adults. In the next section of the paper, the authors review the
      assessment and diagnosis of AUDs in adolescents and consider how findings from
      such assessments will influence subsequent treatment planning. They also describe
      prognostic factors (e.g., family issues, socioeconomic factors, psychiatric
      comorbidity, gender, ability to form a therapeutic alliance) that may affect
      treatment outcome and need to be considered in treatment selection. The various
      settings in which adolescent AUDs may be treated and the types of patients and
      situations for which each is most appropriate are described. The second half of
      the article focuses on the treatment of adolescents with AUDs. The authors
      describe techniques for establishing abstinence and then preventing subsequent
      relapse. Although there is an interest in the use of medications (e.g.,
      naltrexone) to treat AUDs in this population, there are unfortunately few if any
      data concerning the use of these agents in adolescent patients. More data are
      available concerning psychosocial treatments. The authors describe a variety of
      psychosocial modalities that have been tested in adolescents, including
      individual psychotherapy (e.g., interpersonal therapy, cognitive-behavioral
      therapy, motivational enhancement therapy), group therapies, 12 step/self-help
      programs, family therapy, skills training for parents, and psychoeducation. The
      authors then consider the importance of targeting comorbid psychiatric
      conditions, especially anxiety and depression, in the treatment of AUDs in
      adolescents. The authors stress the importance of being aware that adolescents
      with AUDs are at increased risk for violence against self or others and suicide.
      They also note that practitioners who work with adolescents with AUDs often need
      to deal with forensic issues (e.g., DUI charges).

PMID- 15985933
TI  - Treatment-refractory mood disorders: a psychodynamic perspective.
AB  - Treatment-refractory mood disorders pose a significant problem for clinicians.
      Although biological approaches are usually emphasized in the treatment of
      patients with these disorders, preliminary findings from an ongoing,
      naturalistic, longitudinal study of treatment outcome support the notion that a
      subset of patients with treatment-refractory mood disorders may respond to
      careful integration of a psychodynamic therapeutic approach into the customary
      biological approaches. Ten psychodynamic principles that appear to be useful in
      work with patients with treatment-refractory mood disorders were identified based
      on a review of the records of 28 patients who were treated using this approach.
      These principles are presented, discussed, and illustrated by material from a
      representative case study.

PMID- 15985934
TI  - A public health response to a cluster of suicidal behaviors: clinical psychiatry,
      prevention, and community health.
AB  - OBJECTIVE: To develop and implement a community public health response to a
      suicidal behavior cluster, including collection of risk factor data in order to
      prevent further behaviors. METHODS: A three-phase response, including school-wide
      educational debriefings, individual screening for referrals, and on-site crisis
      management, was implemented. Incidence of suicidal behaviors and their
      association with hypothesized risk factors were measured. RESULTS: Thirty-three
      percent of students were screened. Depression and poor social functioning were
      associated with an increased risk of suicidal ideation. Poor social functioning
      and school adjustment were associated with an increased risk of suicide attempts.
      CONCLUSIONS: Development and implementation of a timely public health response,
      including elucidation of critical risk factors, might prevent further suicidal
      behaviors.

PMID- 15985936
TI  - HIPAA: a report from the front lines.

PMID- 15985935
TI  - Reproducibility of the in vivo effect of the selective serotonin reuptake
      inhibitors on the in vivo function of cytochrome P450 2D6: an update (part II).

PMID- 15985937
TI  - Back to basics: law and mental health.

PMID- 15985938
TI  - Ziprasidone substitution in a patient with risperidone-induced
      hyperprolactinemia.

PMID- 15985939
TI  - Virtual Briefcase-Psych network version 2.0.

PMID- 15985940
TI  - Perception of depot antipsychotics by mental health professionals.
AB  - OBJECTIVE: This study examines attitudes of mental health professionals about the
      use and usefulness of depot antipsychotic medications and determines similarities
      and differences in attitudes between professional groups. METHODS: Mental health
      professionals working with patients with severe mental illness completed a
      questionnaire designed to evaluate their opinions concerning rate of depot use,
      indications for use of depots, problems with use of depots, common side effects
      of depots, barriers to switching from depot to oral atypical antipsychotics,
      impact of staffing levels on drug choice, and relative confidence in various
      antipsychotics for the management of chronic psychosis. RESULTS: Overall, all
      professional groups perceived depot antipsychotics as a requirement for the
      treatment of those with serious mental illness who were poorly adherent. However,
      there were a number of professional differences in responses to certain items in
      the survey that probably reflected the degree of direct contact with patients.
      Medical staff were remarkably uniform in their opinions on the use and usefulness
      of depots. Mental health staff from all the professional groups surveyed
      considered extrapyramidal side effects (EPS) a major concern, while few rated
      cognitive side effects, sexual side effects, and weight gain as significant
      concerns, even though these problems are reported to be a principal concern of
      patients. Although all professional groups indicated an awareness of the
      potential toxicity of depot antipsychotics and there was an overall consensus
      that atypical antipsychotics are likely to be beneficial in chronic psychosis,
      limitations in resources were seen as a barrier to switching. CONCLUSIONS:
      Attitudes concerning the usefulness and rationale for use of depot antipsychotics
      differ by medical profession. Nursing and allied health workers are more likely
      than medical staff to note patient specific variables such as weight gain,
      injection site reactions, and patient preferences as problems with depots. The
      results also suggest that, in a community-based psychiatric care system, the use
      of newer and potentially better agents for the management of psychosis is
      impaired by resource limitations in service delivery as well as by educational
      disparities between the professions.

PMID- 15985941
TI  - Challenges at the end of the bell-shaped curve.

PMID- 15985942
TI  - Neuroimaging studies of violence and antisocial behavior.
AB  - The neurobiological basis of violence and antisocial behavior is poorly
      understood. Lesion studies have implicated the frontal and temporal lobes in such
      phenomena. Recent neuroimaging studies have provided more detailed information on
      the neurobiological correlates of violence and antisocial behavior. Moreover, the
      results of such imaging studies extend findings from prior lesion studies. These
      results suggest that violent and antisocial behavior is associated with
      disruptions in frontotemporal neural systems. This article reviews the
      neuroimaging literature on violence and antisocial behavior and discusses the
      strengths and weaknesses of the different methods that have been used in such
      studies. The author reviews findings from cerebral psychophysiology studies
      (electroencephalographic studies and evoked potentials), as well as from studies
      using positron emission tomography (PET), single photon emission computed
      tomography (SPECT), and magnetic resonance imaging (MRI). The article concludes
      with a discussion of useful directions for future research. It is clear that the
      use of neuroimaging methods in combination offers the greatest promise for
      progress in the understanding of the neural basis of violence and antisocial
      behavior.

PMID- 15985943
TI  - Borderline patients at the border of treatability: at the intersection of
      borderline, narcissistic, and antisocial personalities.
AB  - The author discusses the difficulties involved in treating patients with
      borderline personality disorder and concomitant Cluster B-narcissistic,
      histrionic, and/or antisocial-personality traits or disorders. He presents eight
      vignettes of patients with borderline personality disorder combined with various
      types of Cluster B personality traits or disorders and describes the course of
      their treatment. The author posits that such patients fall on a continuum ranging
      from difficult to treat but still treatable, to those with strong narcissistic or
      even psychopathic traits whose illness fails to improve no matter what treatment
      methods are applied (i.e., they have "untreatable" illness).

PMID- 15985944
TI  - The value of therapeutic communities in the treatment of personality disorder: a
      suitable place for treatment?
AB  - In the United Kingdom, a government program investigating the links between
      offending and personality disorder has stimulated renewed interest in the
      treatment of personality disorders. One psychosocial treatment option for
      patients with personality disorders is the therapeutic community (TC). In 2000,
      the authors conducted a small qualitative study with a sample of psychiatrists
      which suggested that TCs were not well understood and that the status of evidence
      on efficacy might be partly responsible for low referral numbers. This article
      reviews the evidence for the efficacy and cost-effectiveness of TCs as a
      treatment for personality disorders and considers which types of disorders are
      amenable to TC treatment. We conclude that there is a strong case for more
      rigorous evaluation and that some of the difficulties anticipated in applying
      randomized clinical trial (RCT) methodology to the study of TCs could be
      overcome.

PMID- 15985945
TI  - Psychiatric advance directives.
AB  - Psychiatric advance directives are gaining attention as the number of consumers
      seeking metal health services increases. Even though medical advance directives
      have existed for years, psychiatric advance directives are in their infancy. The
      goal of these directives is to increase patient autonomy and decrease coercive
      treatment. Although this concept sounds simple, advance directives have generated
      heated debates that encompass ethics, law, and medicine. Psychiatric advance
      directives are also not universally accepted--only 14 states currently recognize
      such directives. This review article discusses the premise behind psychiatric
      advance directives and explores possible benefits and obstacles to the use of
      such directives.

PMID- 15985946
TI  - Relating clinical trials to psychiatric practice: part I: the case of a 13-year
      old on aripiprazole and fluoxetine.

PMID- 15985947
TI  - Religious issues in psychotherapy.

PMID- 15985948
TI  - Forensic use and abuse of psychological tests: multiscale inventories.

PMID- 15985949
TI  - Effectiveness of antiglucocorticoid therapy in a patient with psychotic
      depression and ectopic ACTH production.

PMID- 15985950
TI  - Hierarchical and nonhierarchical approaches in psychiatric diagnosis: a case
      report of change in psychiatric symptoms and diagnosis over time.
AB  - The article reports the case of a 39-year-old male who was diagnosed with and
      treated for bipolar disorder. Over the past 18 months, the patient has
      experienced new onset of auditory hallucinations and worsening of his psychotic
      symptoms. The treating psychiatrists changed the diagnosis from bipolar disorder
      to schizoaffective disorder. The authors discuss hierarchical and nonhierarchical
      approaches to psychiatric diagnosis in relation to this case report.

PMID- 15985951
TI  - Progressing and remembering.

PMID- 15985952
TI  - Optimizing lithium treatment in bipolar disorder: a review of the literature and
      clinical recommendations.
AB  - While the past decade has witnessed a major proliferation of putative treatments
      for bipolar disorder, one medication--lithium--has proven its effectiveness
      through 50 years of clinical experience and scientific scrutiny. Unfortunately,
      because the generic compound, lithium, lacks the financial support of its newer,
      patented comparators, it is often neglected by clinicians who are exposed to
      continuing medical education (CME) and residency training programs that are
      heavily weighted towards the newer treatments. This article critically examines
      the medical literature on lithium's efficacy, anti-suicidal properties, and
      adverse effects. The authors present research-based recommendations for
      maximizing lithium's benefits and minimizing adverse effects associated with
      lithium in patients with bipolar disorder.

PMID- 15985953
TI  - Hyperprolactinemia and schizophrenia: mechanisms and clinical aspects.
AB  - The association between elevated prolactin levels and conventional antipsychotics
      is well-established. The novel antipsychotic, risperidone, has also been shown to
      elevate prolactin levels. Patients undergoing treatment with these medications
      are at high risk for developing hyperprolactinemia, which is associated with
      decreased bone mineral density, osteoporosis, menstrual disruptions and
      infertility, galactorrhea, breast cancer, cardiovascular disorders, and sexual
      impairment. Patients treated with conventional antipsychotics and risperidone
      should be routinely screened for hyperprolactinemia, and monitored for known
      sequelae. Optimally, patients with hyperprolactinemia secondary to antipsychotic
      drug treatment should be switched to a prolactin-sparing antipsychotic. This
      review will briefly highlight the regulation and function of prolactin secretion,
      discuss clinical effects of antipsychotic-induced hyperprolactinemia, and suggest
      a course of treatment.

PMID- 15985954
TI  - Diagnosis and treatment of chronic depression in children and adolescents.
AB  - Chronic unipolar depression is being increasingly recognized in general
      psychiatry as a particularly severe form of depressive illness that leads to
      significant symptomatology, prolonged suffering, and prolonged functional
      impairment in a variety of domains, including educational/vocational dysfunction
      as well as interpersonal impairment. Recent research on treatment interventions
      for adult patients with chronic depressions suggests that standard treatments for
      depressive illness may need modification to benefit patients with chronic
      illness. Little attention at this point has been given to the problem of chronic
      depression in children and adolescents. Many adults with chronic depressive
      disorders had onset of depression in their childhood or adolescence, making early
      identification of this form of illness a priority. The authors present a
      comprehensive review of emerging literature in the assessment, clinical course,
      and treatment of chronic forms of unipolar depression in youth. They then develop
      summary recommendations for the assessment and treatment of this type of mood
      disorder in youth, based on the currently available research and common sense
      clinical experience.

PMID- 15985955
TI  - Trauma-related mental health needs and service utilization among female veterans.
AB  - Women constitute a growing segment of the military veteran population and
      researchers have begun to examine the extent to which their mental health needs
      are appropriately addressed within the Veterans Affairs (VA) healthcare system.
      Existing research documents high rates of both military and non-military trauma
      among female veterans; however, little has been done to examine the extent to
      which female veterans exposed to trauma receive treatment for trauma-related
      problems such as posttraumatic stress disorder (PTSD) and substance abuse within
      the VA system. This article reviews the literature documenting a high rate of
      trauma exposure among female veterans and examines evidence that trauma-related
      mental health problems, such as PTSD and substance-use problems, are under
      diagnosed and under-treated among female veterans in VA healthcare settings. The
      few available studies examining general service utilization among female veterans
      are also reviewed, and implications for future research and clinical practice in
      the area of female veterans' trauma-related mental health needs and service use
      patterns are discussed. In order to provide more accurate assessments of female
      veterans' trauma-related mental health needs, researchers are encouraged to
      implement comprehensive trauma assessments as well as clinically valid PTSD and
      substance abuse diagnostic assessments. Researchers are also encouraged to
      examine the availability and efficacy of both VA and non-VA mental health
      services to determine the appropriateness of women's VA service use patterns.
      Clinicians providing VA mental health services for women are encouraged to
      include comprehensive, behaviorally-specific trauma interviews and diagnostic
      evaluations for PTSD and substance-related problems in their standard assessment
      protocols.

PMID- 15985957
TI  - A psychodynamic perspective on anxiety.

PMID- 15985956
TI  - Classification of neuropsychiatric medications by principal mechanism of action:
      a meaningful way to anticipate pharmacodynamically mediated drug interactions.

PMID- 15985958
TI  - Expert evaluation, controversial cases, and the media.

PMID- 15985959
TI  - QuickLink Pen v 1.55.

PMID- 15985960
TI  - A paradigm for treatment of inpatient psychiatric disorders: from asylum to
      intensive care.
AB  - OBJECTIVE: No articles, chapters, or texts have been published in the last 5
      years that detail a workable model of inpatient psychiatric treatment based on
      current, drastically changed realities. METHODS: We reviewed controlled studies
      on inpatient psychiatric care and pooled our clinical experience from two
      academic inpatient units and a Veterans Affairs inpatient unit. RESULTS: Major
      changes in systems of care, the population now being hospitalized, the emphasis
      on practicing evidence-based medicine, and decreased funding of inpatient
      psychiatric units have necessitated changes in the traditional paradigm of
      inpatient treatment. We describe the functions that an inpatient unit performs
      best and detail 1) objectives of treatment with an emphasis on the "focal
      problem", and 2) the specific treatment interventions, treatment team members,
      and outpatient links necessary to maximize post-hospital outcome for patient and
      family. CONCLUSION: Given current realities, the treatment paradigm that we
      recommend has evolved from an asylum-like long-stay model to one that is more
      like a medical-surgical intensive care unit with an emphasis on rapid diagnosis,
      psychopharmacological intervention, and laying the groundwork for effective
      outpatient management. In consequence, the expected clinical outcomes from an
      episode of inpatient psychiatric treatment are quite different from those of the
      recent past.

PMID- 15985961
TI  - Psyche and soma.

PMID- 15985963
TI  - Abortion and psychiatric practice.

PMID- 15985964
TI  - Cardiovascular health and depression.
AB  - Research has shown that depression increases the likelihood that otherwise
      healthy people will develop ischemic heart disease (IHD) and worsens the
      prognosis of patients who already have IHD. Moreover, concerns about safety
      (e.g., cardiac side effects, drug-drug interactions) have caused physicians to be
      hesitant about using antidepressant agents in patients with IHD. This article is
      based on a recent roundtable of experts who met to discuss risk, diagnosis, and
      treatment options for depression in patients with IHD. This article reviews
      clinical and epidemiological studies that have described a link between
      depression and the subsequent development of IHD and have examined the role of
      depression as a predictor of cardiac events in patients with existing IHD. The
      article addresses the issue of whether depression can be safely and efficaciously
      treated both in patients with stable IHD and in those with acute coronary
      syndromes. The authors discuss safety issues related to the potential for
      interactions between antidepressants and cardiovascular medications, the use of
      nonpharmacologic treatment options such as psychosocial interventions, and the
      effect of antidepressant therapy on quality of life in patients with IHD. The
      article concludes with practical clinical guidance concerning the management of
      depression in patients who have recently experienced myocardial infarction.

PMID- 15985965
TI  - The cholinesterase inhibitors.
AB  - Dementia is a serious and growing problem that presents enormous burdens to
      patients, their families, and national healthcare systems throughout the world.
      In the United States, there are currently two classes of psychopharmacologic
      agents approved for the treatment of Alzheimer's disease: the cholinesterase
      inhibitors, which are approved for use in patients with mild to moderate disease,
      and memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, which is
      approved for treatment of moderate to severe illness. Three cholinesterase
      inhibitors are in general clinical use, each of which has a distinct
      pharmacokinetic, pharmacodynamic, and side-effect profile. In addition, there is
      growing research and clinical evidence of the effectiveness of the cholinesterase
      inhibitors in patients who are in the more advanced stages of Alzheimer's
      dementia as well as in patients with other forms of dementia.

PMID- 15985966
TI  - Emerging psychotherapies for eating disorders.
AB  - Eating disorders are serious illnesses associated with significant medical and
      psychological sequelae and, in the case of anorexia nervosa, significant
      mortality. Established psychotherapies such as cognitive-behavioral therapy and
      interpersonal therapy are effective for many patients with eating disorders.
      However, these treatments fail to yield full long-term remission in a substantial
      number of patients. There is a need for novel psychotherapeutic approaches for
      patients with eating disorders. The authors review three promising new treatment
      approaches in the field of eating disorders. Motivational enhancement therapy is
      based on established motivational principles for treating patients with addictive
      disorders and has been adapted as an early component of treatment for patients
      with anorexia nervosa and bulimia nervosa. Dialectical behavioral therapy was
      initially developed for the treatment of borderline personality disorder and has
      been successfully applied to patients with binge eating. A novel form of family
      therapy, the Maudsley family treatment for adolescents with anorexia nervosa, has
      been newly manualized, and studies using this treatment are ongoing. For each
      treatment, the authors review the theory and techniques of treatment and then go
      on to review existing data on treatment efficacy.

PMID- 15985967
TI  - The causes of schizophrenia: neurodevelopment and other risk factors.
AB  - Understanding the etiology of schizophrenia has been a considerable challenge.
      The neurodevelopmental hypothesis has held sway in recent years, focusing our
      attention on biological causes acting in early life. Much evidence supports this
      hypothesis and risk factors operating in early life (e.g., obstetric
      complications) have been shown to be associated with the later development of
      schizophrenia. Indicators of abnormal neurodevelopment that characterize
      individuals vulnerable to later developing schizophrenia have also been
      identified. For example, as a group, children who will later develop
      schizophrenia subtly differ from their peers in terms of their motor, cognitive,
      and social functioning. However, there is much that cannot be explained in purely
      neurodevelopmental terms. There is growing evidence of associations between the
      risk of schizophrenia and factors such as drug misuse, ethnicity/migration, life
      events, and urbanicity. A multifactorial model of causation that encompasses
      biological, social, and psychological elements is arguably both a better
      representation of current research findings and a more appropriate model for
      clinical practice.

PMID- 15985968
TI  - Relating clinical trials to psychiatric practice: part II: the gap between the
      usual patient in registration trials and in practice.

PMID- 15985969
TI  - Insight, consciousness, learning, and change.

PMID- 15985970
TI  - Juveniles standing trial: waiver to adult court.

PMID- 15985971
TI  - Ziprasidone for dementia in elderly patients: case review.
AB  - Treatment of elderly patients with dementia-related behavioral disturbances and
      depression-related psychosis poses a significant problem, considering patients'
      frailty and use of polypharmacy for comorbid medical disorders. This case series
      describes the use of ziprasidone, a novel atypical antipsychotic, in three frail,
      elderly patients admitted to the hospital for behavioral disturbances secondary
      to dementia-related illness after their current treatment failed to improve
      symptoms or produced intolerable side effects. At admission, none of the patients
      were taking medications contraindicated for use with ziprasidone. In each case,
      ziprasidone resolved symptoms of agitation, psychosis, depression, and cognitive
      impairment sufficiently to permit discharge on maintenance therapy to assisted
      living facilities or nursing homes. No patient suffered syncope or postural
      hypotension during treatment with ziprasidone. Electrocardiograms taken on
      admission and after institution of ziprasidone disclosed minimal increases in the
      QTc interval or no change from baseline, and no patient had a QTc interval > 500
      ms. No drug-drug interactions occurred. Similar results were observed in an
      additional 53 of 62 elderly patients (aged 64-92 years) admitted to our
      institution. This experience suggests that ziprasidone is a safe and effective
      treatment option in elderly individuals who require antipsychotic medication.

PMID- 15985972
TI  - The role of artificial cells in cell and organ transplantation in regenerative
      medicine.
AB  - Potential applications of artificial cells include cell therapy, gene therapy,
      enzyme therapy, blood substitutes, drug carriers and many other areas. Only 2
      examples will be discussed here. One is the use of artificial cells containing
      cells with emphasis of the use of hepatocytes for short term implantation in
      acute liver failure as temporary liver support so as to allow the liver to
      regenerate. Another example is the use of artificial red blood cells (RBC) as
      oxygen carrier so as to allow the bone marrow to regenerate the needed RBC.

PMID- 15985973
TI  - Artificial lung and extracorporeal gas exchange.
AB  - Over the last years, several observational studies have suggested that
      extracorporeal lung assist (ECLA) may be an important contribution to clinical
      algorithms for the treatment of most severe acute respiratory distress syndrome
      (ARDS). Today ECLA is used only as a rescue therapy in life threatening gas
      exchange disorders if maximal conventional therapy fails to prevent from
      hypoxemia. With subsequent reduction of complications and improvement of
      biocompability, extracorporeal membrane oxygentation (ECMO) indications may be
      extendend to treat patients earlier and not only in rescue situations along the
      original idea to buy the lung some time to heal by avoiding further ventilator
      associated lung injury. Veno-venous ECMO therapy at present is an important
      therapeutic option in severe ARDS with persisiting life threatening gas exchange
      disorder as a rescue therapy. The development of smaller, less complex and more
      secure ECMO or pumpless veno-arterial ECLA systems has the potential to perform
      controlled studies of its use in ARDS and potentially expand indications.

PMID- 15985974
TI  - The role of peritoneal dialysis in renal replacement therapy: an update on
      medical aspects.
AB  - In this brief review, we discuss various medical factors that are of importance
      for the role of peritoneal dialysis (PD) in renal replacement therapy (RRT),
      whereas the complex role of non medical factors will only be mentioned briefly.
      The aim of any RRT, including hemodialysis, PD and renal transplantation, is to
      normalize the volume and composition of the body fluids, to remove uremic toxins,
      and to improve clinical outcome. In the following, we will focus on adequacy,
      preservation of residual renal function, fluid balance, infections, nutrition,
      cardiovascular disease and systemic inflammation in PD as these factors are
      strong predictors of clinical outcome in end stage renal disease patients.

PMID- 15985975
TI  - Hepatic assist devices.
AB  - Acute liver failure (ALF) is associated with significant morbidity and mortality.
      Better understanding of the pathophysiology of the disease and improvements in
      patient management have resulted in increased survival. Liver transplantation
      remains the only proven therapeutic modality. Primarily because of organ donor
      shortage, a number of strategies have been developed in an attempt to support
      patients with severe ALF until either an organ becomes available for
      transplantation or until they recover. Liver support strategies include use of
      either non-biological or biological systems. Non-biological systems include
      plasma exchange, hemodialysis, hemofiltration, charcoal and resin hemoperfusion.
      These systems are able to remove toxins, but their utility is limited by their
      inability to provide missing liver synthetic function. Biological liver support
      systems include ex vivo liver perfusion and use of hepatocyte-based
      extracorporeal devices. Like non-biological systems, biological ones provide a
      means of detoxification and in addition biotransformation and biosynthetic
      functions. The major limitation of these systems is the lack of availability of
      an effective highly differentiated human hepatocyte line for clinical use.
      Currently clinically tested liver support systems use either porcine hepatocytes
      or human hepatoma cell lines. As liver support therapy evolves, there will be a
      role for both biological and non-biological liver support systems to treat
      specific forms of liver failure.

PMID- 15985976
TI  - From stem cells to insulin-producing cells: towards a bioartificial endocrine
      pancreas.
AB  - The total absence or low production of insulin by beta-cells avoids a proper
      control of glycemia forcing diabetic people to daily insulin injection for
      survival. Islet transplantation represents a hallmark in the cure of diabetes and
      has been successfully applied to more than 400 patients, resulting in insulin
      independency for periods longer than 4 years. However, transplantation trials for
      diabetes have to face the scarcity of islets from cadaveric donors. Therefore,
      the finding of renewable sources of cells could circumvent this problem. In this
      respect, embryonic or adult stem cells are representing an interesting
      alternative. Stem cells display robust proliferation and the plasticity to
      differentiate to other cell types, including insulin-containing cells. The
      current therapeutical use in the future of bioengineered insulin-secreting cells
      derived from stem cells needs at present to fulfill several criteria. These
      criteria concern to the type of stem cell to be used as starting biomaterial
      (embryonic or adult), the in vitro differentiation protocol applied, the
      functional phenotype reached for the final cell product and the transplantation
      associated problems (likely immune rejection and tumor formation). This review
      will try to focus on these different aspects in order to emphasize in the key
      points to consider for designing unified strategies for diabetes cell therapy.

PMID- 15985977
TI  - Tissue engineering of skin substitutes.
AB  - Cultivated epithelial autografts as multilayered thin sheets represent common
      standard in clinically applied tissue engineering substitutes, outnumbering all
      experimental alternatives. However, the unsatisfying short and long term results
      concerning mechanical stability and scarring demand for alternatives. Our group
      investigated cultivation and transplantation of cultured autologous keratinocytes
      as a single cell suspension in a fibrin sealant matrix in athymic mice in
      combination with allogenic skin grafting. We observed reliable wound
      reepithialization after a cultivation period of only 2 weeks. Additionally, we
      could allocate successful combination of a keratinocyte fibrin sealant suspension
      and acellular dermis in an attempt to regenerate full thickness skin defects in a
      pig animal model. The potential clinical implication of subconfluently cultured
      keratinocytes is enhanced by the possibility of co-transplantation with
      decellularized dermis.

PMID- 15985978
TI  - Association between Crohn's disease and Conn's syndrome. A report of two cases.
AB  - The natural history of Crohn's disease (CD) is characterised by periods of
      remission followed by phases of flares. Persistent or intractable diarrhoea may
      be associated with ileal disease or arise following ileal resection, resulting in
      potassium depletion. Medical therapy with steroids presents troublesome side
      effects (e.g. hypertension). Conn's syndrome, caused by unilateral aldosterone
      producing adenoma, is characterised by clinical features including hypokalaemia
      and hypertension. Thus, CD and Conn's syndrome may have an overlap of
      manifestations, and up to now, the simultaneous occurrence of these conditions
      has not been described. We report here 2 cases of association between CD and
      Conn's syndrome.

PMID- 15985979
TI  - Infection in ICU: a burden without solution?

PMID- 15985980
TI  - Periodontal disease as a risk factor in pregnancy.
AB  - There is growing evidence that periodontal disease represents a risk factor for
      preterm delivery and premature membrane rupture. To prevent an oral inflammatory
      process evolving into a full-blown form of periodontitis, with possible severe
      repercussions on pregnancy outcome following systemic spread, future mothers
      should receive regular professional oral hygiene care throughout pregnancy.

PMID- 15985981
TI  - Pharmacologic treatment of the dysfunctional patient.
AB  - It is common knowledge that therapeutical approach of temporomandibular disorders
      (TMD) is multidisciplinary and directed to remove the cause of disorder, to
      eliminate symptomatology and to make an improvement to patient's life. Most of
      the subjects observed have pain, often caused by muscular component (90-95%) and
      rarely by the intercapsule. Generally, it deals with chronic-ache, bound by a
      layer of stress and by considerable emotionalism. A correct diagnosis is the
      indispensable requirement for the drugs prescription, not only, but remarkable
      is: to attach importance to the knowledge of workings action, the side effects
      and active principals contraindications took into account. This article will be a
      question of medicines which are the basis of medical therapy for temporal-jaw
      excess with: analgesic, antinflammatory, short-relaxing and tranquillizer,
      tricyclical antidepressant and local anesthetic. As regards to TMD, notice that
      pharmacological therapy must not be over protracted for too much time, especially
      for use of benzodiazepine and tricyclic antidepressants, dosage demanded are
      decisively less if we compare, usually main therapeutical indications. The
      pharmacological therapy can be an agent for competent method for symptomatology
      treatment of temporal-jaw disorder but, patient must be acquainted about a fact,
      trouble often could not disappear only with a drug. To conclude, we can assert
      that the right use of medicines, in addition with physiotherapeutical therapy and
      an occlusal splint, represent the most efficient means to deal with the majority
      of temporal-jaw diseases.

PMID- 15985982
TI  - The aesthetic and functional restoration in the case of partial edentulism in
      young patients.
AB  - The absence of teeth in youths can be due to congenital absence, traumas, caries
      and periodontitis. The loss of a tooth in growing patients can cause both
      aesthetic-functional and psychological problems, particularly if the teeth of the
      anterior region are involved. When there is the loss of a dental element in a
      teenager it is necessary to provide a quick suitable therapeutic solution, which
      will be different in comparison to an adult because of the changes related to the
      growth of the maxillary bones. The aim of this paper is the analysis of the
      several therapies which can be carried out on young patients with partial
      edentulism, paying particular attention to the conditions and the indications
      which allow an implant prosthesis restoration.

PMID- 15985983
TI  - Cephalometric evaluation of the upper airway in patients with complete dentures.
AB  - AIM: Obstructive sleep apnea syndrome (OSAS) is a disorder characterised by
      repeated obstructions of the upper airway, with consequent episodes of apnea and
      hypopnea during sleep, snoring, and daytime sleepiness. Recently, a role of
      edentulism in the occurrence or in the worsening of this disorder was suspected.
      The aim of the study was to assess, through a cephalometric analysis, if the
      removal of denture induces, and where, modifications that can favour the pharynx
      collapse. METHODS: A total of 27 subjects with complete or partial loss of teeth
      and with heavy loss of the vertical dimension, were examined. The patients were
      submitted to radiographs of the cranium in supine position, to simulate as much
      as possible the night condition, with the denture in intercuspal position (ICP),
      and in relaxed position both with denture (D-RP) and without it (edentule-relaxed
      position, E-RP). The radiographs were analysed through specific measures for OSA
      evaluating the parameters that could be modified by the denture. RESULTS: The
      pharyngeal airway space (PAS) decreases, at the level of uvula, from ICP (6.7 mm)
      to RP (5.3 mm) (P< 0.05). The distance between the base and the tip of the tongue
      significatively decreased both from ICP vs E-RP (7.35 mm vs 6.87 mm; P< 0.05),
      both from D-RP to E-RP (7.22 mm vs 6.87 mm; P< 0.005). CONCLUSIONS: From the data
      obtained from the cephalometric analysis it seems that wearing denture induces
      modifications in the position of the tongue, of the jaw and of the pharyngeal
      airway space that can favour the reduction of apnea episodes.

PMID- 15985984
TI  - Expression of contact allergy in undergoing prosthodontic therapy patients with
      oral diseases.
AB  - AIM: Contact allergy is a postponed reaction of hypersensitivity where a
      localised cutaneous or mucosal lesion occurs due to a recurrent contact with an
      allergen. Placement of a fixed or removable prosthetic replacement into the oral
      cavity causes corrosive processes on the surface of the restoration and discharge
      of ions, which as haptens can induce allergic reactions. The purpose of this
      study was to examine occurrence of allergies to basic and auxiliary restorative
      dental materials in patients with lichen, stomatitis and stomatopyrosis by means
      of an epicutaneous allergy test. METHODS: The study included 32 patients with a
      fixed and/or removable replacement and 7 patients with one of the mentioned
      diagnoses, but without any replacement. Testing was conducted using a standard
      method (patch test), and hypersensitivity to 13 most common allergens in
      prosthodontics was examined. RESULTS: The research results revealed higher
      frequency of positive allergic reactions in persons with the mentioned diseases
      and with a restoration. Patients with lichen indicated positive patch test in the
      majority of cases. The allergens of nickel, cobalt and chromium demonstrated the
      highest score of positive results, and negative score was found for
      dibutylphthalate and HH mix. Stomatopyrosis was more common in persons with
      hypersensitivity to chromium. A lower incidence of positive allergic reactions to
      epoxide resins was found in female than in male subjects. CONCLUSIONS: The
      epicutaneous (patch) test performed in the subjects examined in this study,
      showed that the majority of positive reactions was caused by mixes of nickel,
      cobalt and chromium; however, unwanted reactions also to other auxiliary
      materials used in dental practice should also be considered.

PMID- 15985985
TI  - Non-surgical periodontal therapy of cyclosporin A gingival overgrowth in organ
      transplant patients. Clinical results at 12 months.
AB  - AIM: The aim of the present study was to evaluate the clinical effects of non
      surgical and supportive periodontal treatment on cyclosporin A-induced (CsA)
      gingival overgrowth (GO) in a group of transplant patients. METHODS: Thirty
      patients received etiological periodontal treatment and were placed in a -two
      monthly recall program for 12 months. Plaque index, bleeding index, probing
      depth, degree of GO using the Seymour index (hypertrophy index, HI) and distance
      between the mucogingival junction and the base and the apex of each interdental
      papilla were recorded at baseline and repeated 12 months after treatment.
      RESULTS: At baseline, 22 patients had HI values >30% and were considered as
      ''responders''. A total of 376 gingival units (72.31%) in the anterior segments
      and 376 (54.97%) in the posterior ones presented GO with a mean HI value of 2.22
      +/- 1.95 and 1.24 +/- 1.57, respectively. The etiological treatment resulted in a
      statistically significant improvement of all parameters assessed (P<0.0001). All
      patients had a decrease in the number of affected sites (mean HI values of 0.42
      +/- 0.77 and 0.39 +/- 0.85 in the anterior and posterior segments) and none had
      HI values >30% and any gingival unit with score of 5 at the end of the
      observation period. CONCLUSIONS: Detailed instructions and intense motivation to
      oral home hygiene measures, inserted in an etiological treatment and a two
      monthly maintenance therapy, appear to be effective in controlling the GO and in
      maintaining clinical improvements for prolonged time period.

PMID- 15985986
TI  - Multiple and relapsing supernumerary teeth associated to dens invaginatus. Review
      of the literature and case report.
AB  - The aim of this paper is to show problems related to supernumerary teeth therapy
      according to their formation and mineralization. The clinical case of an 11-year
      old boy suffering from alteration of the eruptive sequence of the upper incisor
      teeth caused by 2 supernumerary teeth in the premaxilla, is reported. What is
      interesting about this case is that after the surgical removal of the
      supernumerary teeth, with a radiographic examination taken 6 months later, 2
      other supernumerary teeth were observed. The authors point out that while the
      clinical approach can be the same for different situations it is not possible to
      have the same approach for the surgical therapy which may be different from case
      to case.

PMID- 15985987
TI  - Sublingual ranula: report of a submandibular clinical case.
AB  - Ranula is a raised mucocele on the oral floor. When the mucocele extends and
      passes the sublingual space and invades the submandibular space it may be called
      ''plunging ranula''. Its etiology is not completely known. Our clinical case is a
      clear example: a 10-year old formation, not painful, developed during several
      years and originally of small dimension located in the sublingual region. The
      purpose of this study is to underline that the surgical treatment of choice, in
      these clinical situations, is the drainage of the cavity and marsupialization
      rather than a radical removal.

PMID- 15985988
TI  - Oncologic surgery: the advantages and disadvantages of minimally invasive
      surgery.
AB  - For the last 15 years, the minimalized traumatization of laparoscopic surgical
      procedures has changed the treatment of numerous diseases. As a result, the
      method has also become an interesting therapeutic alternative for oncological
      indications, too. Nevertheless, its use in the special field of oncology, in
      particular when applied in curative intent, continues to give rise to
      controversial discussion. This paper takes a look at the potential advantages and
      disadvantages of the laparoscopic modality with regard to immune function and
      staging laparoscopy. In view of the fact that, at the present time, curative
      resections are being carried out in relevant numbers, in particular in the field
      of colorectal surgery, the technical feasibility, oncological radicality and
      oncological long-term outcomes are discussed on the basis of the data reported in
      the relevant literature on laparoscopic colorectal surgery.

PMID- 15985989
TI  - Virtual colonoscopy for primary screening. The future is now.
AB  - Virtual colonoscopy (VC) is a minimally invasive tool that utilizes modern CT
      technology for colorectal evaluation. Since its inception in 1994, VC has
      continued to rapidly evolve and improve as a diagnostic screening tool. Early
      success using primary two-dimensional (2D) detection in polyp-rich cohorts was
      followed by disappointing results in low prevalence populations. Subsequent
      introduction of the three-dimensional (3D) endoluminal display for primary polyp
      detection and oral contrast tagging has transformed VC into an effective primary
      screening tool. This state-of-the-art VC technique has already proven to be a
      viable enterprise when combined with existing optical colonoscopy practice. More
      widespread implementation of VC screening faces multiple challenges, but these
      are all greatly overshadowed by the immediate need for increased participation in
      effective colorectal screening. Given its relatively noninvasive nature and the
      wide availability of CT, VC holds significant potential for addressing a very
      important yet preventable public health concern. This review will cover current
      VC technique, compare the existing multi-center VC trials, discuss issues related
      to primary VC screening, and briefly update the progress of our VC screening
      program.

PMID- 15985990
TI  - Treatment of peritoneal surface malignancy by peritonectomy and intraperitoneal
      chemotherapy: a novel therapy with curative potential!
AB  - Peritoneal carcinomatosis has always been regarded to have a poor prognosis.
      Surgery is usually limited to palliation of bowel obstruction by performing an
      intestinal bypass or ostomy. This severe disease has been considered as equal to
      distant metastasis and intravenous (i.v.) chemotherapy is commonly used in order
      to achieve a regression of the tumour. However, resistance to cytotoxic drugs, a
      poor vascular supply and high osmotic pressure might prevent the efficient uptake
      of i.v. chemotherapeutic agents into tumour tissues. A new concept in
      dissemination of gastrointestinal cancer and gynecologic cancer now require that
      peritoneal implants are regarded in a different way. In many patients peritoneal
      dissemination is a locoregional spread of disease with no manifestation of
      systemic disease. A locoregional therapeutic approach combining cytoreductive
      surgery with hyperthermic intraperitoneal intraoperative chemotherapy evolved.
      This new treatment option seems to be an effective therapeutic approach in
      carefully selected patients, and offers a chance for cure or palliation in this
      condition with few alternative treatment options.

PMID- 15985991
TI  - Technical tricks for radical but conservative liver resection. The ultrasound
      guidance.
AB  - Rate of major resection is still high in most surgical institutions due to fear
      of incomplete tumor removal: this is in spite mortality and major morbidity of
      major hepatectomies, particularly in cirrhotic are still not negligible.
      Intraoperative ultrasonography (IOUS), when used not only for tumor staging but
      also for resection guidance, minimises the rate of major hepatectomies
      maintaining treatment radicality. Maintaining this policy, the rate of major
      resection in our experience is 15% if major hepatectomy is classified as removal
      of at least 1 sector or 2 adjacent segments, and 5% if we consider major
      resections only those which include at least 3 segments. This policy has allowed
      us a safe surgical approach with no mortality and minimal major morbidity and
      effective local treatment with no tumor relapses at the site of the resection
      after a mean follow-up of 18 months. Tricks for safe and radical IOUS-guided
      liver resections are here discussed.

PMID- 15985992
TI  - Local recurrences of rectal cancer.
AB  - Data from cancer registries show that incidence of rectal cancer is still high in
      Italy, while mortality rates are slightly decreasing in most recent years.
      Surgery is the treatment of choice and in most cases with curative intent. The
      rectum may be defined as the tract of the large bowel distal to 12 cm from the
      anal verge. Tumors located in that segment show local recurrence rates higher
      than those for tumors located proximally. Pelvic recurrence is evident as a
      regrowth of cancer in and around the tumor bed. Powerful imaging techniques have
      been developed for the early and appropriate evaluation of pelvic recurrences. A
      wide range of recurrence rates after operation for rectal cancer are reported,
      spanning from 3% to over 30%. The main determinants of local recurrence are
      related to the tumor and to the treatment. Among the former, stage at diagnosis
      and number of lymph nodes involved are the most important, along with inadvertent
      perforation of the intestine and location of tumor in the rectum. Among treatment
      factors, type of operation and experience of the operator should be mentioned. A
      major advancement in rectal surgery has been the implementation of total excision
      of the mesorectum. This technique has decreased dramatically recurrence rates of
      rectal cancer, though increasing the risk of local complications. Preoperative
      radiotherapy seems to confer a slight further advantage in selected cases.
      Management of locally recurrent tumors is still unsatisfactory and surgery is
      feasible only in less than 10% of cases.

PMID- 15985993
TI  - [Surgical treatment of breast cancer in the elderly].
AB  - AIM: The aim of this study is to evaluate the prognosis and survival of patients
      aged over 70 years and affected by breast cancer. METHODS: From January 1994
      through December 2000, 56 patients with breast cancer aged 70 years or older were
      submitted to surgical treatment. Associated diseases were present in 24 patients,
      while no patient showed distant metastases at the time of hospital admission. All
      patients underwent breast preserving surgery regardless the tumour size and in 31
      subjects out of 56, the surgical procedure was performed under local anesthesia.
      An axillary lymphectomy was associated in 46 patients. According to the TNM
      staging system, tumours were classified as follows: 10 T1Nx, 18 T1N0, 9 T1N1, 7
      T2N0, 10 T2N1 and 2 T3N1. RESULTS: There was no postoperative mortality and in 6
      cases an axillary seroma was observed. Radiotherapy and tamoxifen treatment
      followed surgery in all cases. The median follow-up was 44 months. Nineteen
      patients (34%) died during the follow-up: 6 patients of cancer progression with a
      specific cancer-death of 10.7% while 13 patients (23.2%) died because of
      concurrent diseases. A local relapse (1.8%) was observed in a single patient 2
      years after the primary surgical treatment and, at 3 years, 37 patients (66%) are
      alive and disease-free. Long-term survival was significantly related to the stage
      of disease at the time of surgery, while our data do not allow any conclusions
      concerning the impact of axillary dissection on long-term outcome. CONCLUSIONS:
      In conclusion, results for breast cancer therapy are comparable in old and young
      patients and therefore strategies and treatment protocols should be similar,
      breast preserving surgery followed by radiotherapy and ormonal treatment being
      ''the gold standard''.

PMID- 15985994
TI  - [Occurrence of synchronous colorectal cancer metastasis in the cirrhotic or fatty
      liver].
AB  - AIM: Metastases from colorectal cancers rarely occur in injured livers, however
      this phenomenon has not been fully investigated in patients with different degree
      of liver damage. Therefore in this study we evaluated the incidence of
      synchronous hepatic metastases in patients with fatty or cirrhotic liver
      submitted to surgery for colorectal neoplasms. METHODS: Seven hundred and forty
      seven patients undergoing surgical treatment for colorectal neoplasms were
      evaluated: the clinicopathological data of 171 patients with liver cirrhosis and
      33 with fatty liver were compared to those of 543 patients without liver damage.
      RESULTS: Gender, age, type of operative procedures performed and histological
      grading were similar in patients with or without liver damage. In patients with
      liver cirrhosis the incidence of stage II tumour was greater, while stage IV
      tumours (P < 0.001) and nodal involvement were significantly lower than in
      patients with non injured or fatty liver (P < 0.02 and P < 0.001 respectively) .
      At the time of surgery, synchronous hepatic metastases were present in 32% of
      patients with normal liver, in 15% of patients with fatty liver (P < 0.02) and in
      4.7% of patients with liver cirrhosis (P < 0.001). CONCLUSIONS: Results of our
      study show that synchronous hepatic metastases of colorectal cancer are less
      frequently observed in patients with fatty or cirrhotic liver than in patients
      with non injured liver, indicating that chronically damaged livers are protected
      from the spread of secondary cancers.

PMID- 15985995
TI  - Topical negative therapy and vacuum assisted closure. New strategies and devices
      in surgical reconstruction.
AB  - Topical negative pressure (TNP) has been introduced in complex surgical
      reconstruction and difficult wound healing, having proven to be effective in both
      drainage of wound secretions and calling for a new, sterile granulating tissue.
      In the last 15 years many reports have been focusing on TNP in different surgical
      specialties (orthopedic surgery in exposed fractures, general surgery in
      eventration, cardiothoracic surgery in sternal dehiscences, plastic surgery in
      difficult wounds and pressure sores). The authors report their personal
      experience being among the first Units to use TNP systematically in Italy.

PMID- 15985996
TI  - Primary signet-ring cell cancer of the lung.

PMID- 15985997
TI  - [Inherited disorders of bilirubin metabolism].
AB  - Jaundice in an infant or older child may reflect accumulation of either
      unconjugated or conjugated bilirubin and could be related to inherited bilirubin
      disorders. Three grades of inherited unconjugated hyperbilirubinemia are
      recognised in humans. This spectrum of disorders is distinguished primarily on
      the basis of the plasma bilirubin level, the response to phenobarbital
      administration, and the presence or absence of bilirubin glucoronides in bile.
      The enzyme responsible for the conjugation of bilirubin is the bilirubin uridine
      diphosphate-glucuronosyltransferase (UGT). Mutations in the gene encoding
      bilirubin-UGT (UGT1A1), lead to complete or partial inactivation of the enzyme
      causing the rare autosomal recessively inherited conditions, Crigler-Najjar
      syndrome type 1 (CN-1) and type 2 (CN-2). Gilbert syndrome (GS) is due to an
      insertional mutation at homozygous state of the TATAA element (seven TA repeats)
      of UGT1A1 producing a reduced level of expression of the gene. The association of
      GS with haemolytic anemias, e.g., Hereditary Spherocytosis (HS) or Congenital
      Dyserythropoietic Anemia type 2 (CDA 2), increase the hyperbilirubinemia level
      and the risk of cholelithiasis. Forms of chronic conjugated hyperbilirubinemia
      are Dubin-Johnson syndrome, Rotor syndrome, Alagille syndrome or arteriohepatic
      dysplasia, Wilson disease or hepatolenticular degeneration. Liver or liver cell
      transplantation is the therapy in some cases.

PMID- 15985998
TI  - [Depressive symptoms and low self-esteem in obese children and adolescents].
AB  - AIM: The aim of th study was to assess the prevalence of depressive symptoms and
      low self-esteem (SE) in a clinical sample of obese children and adolescents; to
      examine whether Body Mass Index (BMI) or age are correlated to scores of
      depression and SE. METHODS: Fifty-five obese patients, aged 9-16 years, completed
      2 questionnaires: the Children's Depression Inventory (CDI) and the
      Multidimensional Self Concept Scale (MSCS), which assesses global SE and 6
      specific domains of SE (Social, Competence, Affect, Academic, Family and
      Physical). RESULTS: The prevalence of depressive symptoms and low global SE was
      not significantly different from normative data of the general pediatric
      population. The mean overall scores on CDI (8+/-4.69) and MSCS (96.6+/-11.54)
      fell within the normal range (0-19 and 85-115, respectively). The lowest scores
      in specific domains of MSCS were obtained in Physical SE (94.42+/-12.64). The
      scores on questionnaires were not significantly correlated to BMI or age. A
      significant negative correlation between Physical SE scores and CDI scores was
      found (r=-0.43; p<0.05). CONCLUSIONS: Obese children and adolescents, as a whole,
      did not present more depressive symptoms and lower SE than the general pediatric
      population. However, some obese patients may be at higher risk for
      psychopathology. In this study, the degree of obesity (BMI), age and sex were not
      risk factors for psychopathology. The relative low scores on Physical SE and
      their correlation to CDI scores suggest that body image dissatisfaction may be a
      risk factor for psychopathology in a subgroup of obese patients.

PMID- 15985999
TI  - [Children of homoparental families: psychological and sexual development].
AB  - AIM: In the last few years some studies have been made about homosexual
      parenthood and especially if this interferes with the child's development,
      identity and future sexual tendency. These studies prove that the parents'
      homosexuality does not seem to compromise the child's psychosexual development
      and that the child's possible homosexuality does not depend on the parents'
      sexual behaviour but on different factors linked to the relationship; as a matter
      of fact there are no relevant differences in the occurrence of homosexuality in
      children born from homosexual and heterosexual parents. The present study
      investigated the psychological and sexual development in a group of children of
      homoparental family. METHODS: The sample observed included 37 children, 22 male
      and 15 female. The following psychodiagnostic tests were used for assessment:
      spontaneous drawing, draw-a-person test, family drawing, blacky pictures test.
      The developmental of the child's sexual identity was determined through the
      preferences and fantasies he/she showed while playing, in the relationship with
      his/her mates, in the way of dressing. We used interviews with the child and the
      parents. RESULTS: All the children showed a good adherence to their sexual role.
      The observations and interviews proved that the children's disorders are not
      linked to the parents' homosexuality. CONCLUSIONS: Being brought up by homosexual
      parents does not seem to compromise the child's future sexual tendency. However,
      in these children the sexual preference could change in adult life, being
      influenced by future situations and circumstances.

PMID- 15986000
TI  - Growth and other factors affecting peak expiratory flow in Greek children.
AB  - AIM: The estimation of peak expiratory flow (PEF) in children is a very easy and
      practical way to check lung function and helps in the diagnosis, treatment follow
      up and evaluation of the development of chronic obstructive pulmonary disease.
      METHODS: Using a Mini-Wright flowmeter (Clement Clarke International Ltd,
      England), we studied the Peak Expiratory Flow (PEF) of 7,067 healthy Greek
      children of age range 6-17 years. All the children have a height ranging between
      mean value+/-2 Standard Deviations for age and sex. RESULTS: The results were
      correlated with age, weight, height and triceps skinfold thickness. The mean
      value of PEF was higher in boys than in girls at all ages, except from the age of
      12-13 years. Our results have shown a very strong relationship between PEF and
      age up to the age of 11 years (P<0.005) but we didn't find such a relationship in
      older children as regards PEF and height (P<0.001). No positive correlation
      between PEF and weight or between PEF and triceps skinfold, was found (P > or
      =0.05). Moreover, a considerable difference in PEF values was found in the
      various groups of every age and sex according to height. CONCLUSIONS: These
      results indicate that height should always be considered in order to estimate PEF
      value. The values of this study (mean and percentiles) were compared to those of
      other studies. Finally, we recommend that the results of this study should be
      used as standards for Greek children.

PMID- 15986001
TI  - [Breastfeeding and health promotion of child: survey results in Molise region].
AB  - AIM: The aim of this study is to compare initiation and duration rates of
      breastfeeding in Molise region (Italy) to those targeted from World Health
      Organization (WHO), and to examine factors associated with infant health.
      METHODS: Trained caregivers administered interviews to 430 mothers whose infants
      were receiving the 2nd dose of compulsory immunisation in 4 primary health care
      centers (ASL) of Molise region, during October-December 2001. Type of
      breastfeeding was classified as predominant or partial, according to the WHO
      definitions. RESULTS: The rate of breastfeeding initiation was 92%, dropping to
      30% when infants were 6 months of age. We found strong differences among the 4
      health care centers involved in the study. Lacking of support after discharge,
      non-breastfed previous child, receiving infant formulas, breastfeeding on
      schedule, rooming-in not effected at hospital, both maternal and familiar
      smoking, were significantly associated with early breastfeeding cessation. The
      rate of iodine supplemented salt consuming was 40%; the rate of mothers who knew
      the importance of using folic acid in preconceptional age was 19%; only 1/3 of
      infants (34%) was placed back to sleep. CONCLUSIONS: Although we meet WHO goals
      regarding breastfeeding initiation, we don't about breastfeeding duration, yet.
      Moreover, the leading factors negatively linked to infant health, are not widely
      recognized. It is therefore necessary to promote the whole infant health, either
      supporting predominantly breastfeeding, especially in some ASL, or providing
      better knowledge about risk factors.

PMID- 15986002
TI  - The head-up tilt test and the differential diagnosis between epileptic attacks
      and syncope. Case report.
AB  - Often patients who have undergone a false diagnosis of epileptic attack have
      actually been affected by syncope. One of the most common causes of such
      misdiagnosis is an abnormal interictal electroencephalographic (EEG) trace. The
      purpose of this paper is to suggest the usefulness of the head-up tilt test as a
      differential diagnosis between epileptic attack and syncope. Patients underwent
      the head-up tilt test, which was considered positive only if the syncopal
      symptomatology was reproduced. The subjects were patients in a neuropsychiatric
      clinic. Four patients with a positive anamnesis due to brief episodes of
      unconsciousness and to falls were assessed. All 4 patients showed an abnormal EEG
      with focal spikes and sharp-waves. The head-up tilt test produced a syncope in
      all 4 cases. In the symptomatology evoked by the test the patients and their
      parents recognized the exact same characteristics of those episodes for which
      they had sought consultation, so a diagnosis of a vasovagal syncope of 3
      different types was made. The head-up tilt test proved appropriate to
      differentiate syncope from epileptic attacks in patients with symptoms of
      unconsciousness, falls and interictal EEG spikes or sharp-waves.

PMID- 15986003
TI  - [Cerebral venous sinuses thrombosis in an infant with supramitral obstructive
      membrane associated with partial anomalous pulmonary venous return].
AB  - Cerebral venous thrombosis is quite rare in newborn infants, but probably its
      incidence is not well evaluated because clinical signs and cerebral
      echocardiography are not specific. We report the case of an newborn infant with
      massive cerebral venous thrombosis associated with heart malformation:
      supramitral ring and partial anomalous pulmonary venous connection in the
      superior vena cava.

PMID- 15986004
TI  - Echocardiography in cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is a new treatment modality for eligible
      patients with congestive heart failure (CHF). The premise of CRT is that it
      decreases inter and intra ventricular inhomogeneity during systolic contraction
      thereby improving efficiency of cardiac pump function. Presence of cardiac
      dyssynchrony appears to be a prerequisite for a response to CRT. Traditionally
      this inhomogeneity in contraction has been determined by electrocardiographic QRS
      widening. More recently several echocardiographic methods of assessment of
      dyssynchrony have become available. These methods utilize conventional M-mode and
      pulsed wave (PW) Doppler as well tissue Doppler imaging (TDI) METHODS: These
      echocardiographic parameters have been shown to be more important predictors of
      response to CRT than conventional QRS widening. This article will discuss
      echocardiographic methods of assessment of dyssynchrony and their role in
      predicting response to CRT. In addition role of echocardiography in post CRT
      pacemaker programming will also be discussed.

PMID- 15986005
TI  - Echocardiographic advances in atrial fibrillation and supraventricular
      arrhythmias.
AB  - Advances in echocardiography have paved the way for the development of
      intracardiac catheters with ultrasound transducers mounted on its tip. With this
      technology it has become possible for the interventional electrophysiologist to
      perform continuous echocardiographic examination during a procedure without the
      need for general anaesthesia or additional staff. Intracardiac echocardiography
      (ICE) allows the monitoring of catheter movement in real-time, assessment of
      catheter-tissue contact and potentially prevents and recognizes complications
      like thrombus formation and pericardial effusion. In addition recent technologies
      allow acquiring the full spectrum of Doppler-imaging permitting evaluation of
      haemodynamic data during the procedure. All these advances have made ICE an ideal
      tool for the interventional electrophysiologist, serving as a diagnostic and
      imaging tool during invasive electrophysiological procedures. This review will
      summarize currently available technology of ICE and its indications and
      applications in electrophysiological procedures.

PMID- 15986006
TI  - Echocardiography in adults with congenital heart disease.
AB  - Echocardiography is a valuable tool in the investigation and follow-up of adult
      patients with congenital heart disease. The majority of these patients have been
      recognised and treated in childhood, and effective investigations in adult life
      depend on exact knowledge of the patient history and previous
      treatments/operations. The major lesions are presented and important
      echocardiographic features briefly discussed.

PMID- 15986007
TI  - Fetal echocardiography. A sophisticated tool in obstetrics.
AB  - Fetal cardiology has been evolving as an exciting speciality over the last 20
      years or so. Whilst much is due to technical advances in fetal echocardiographic
      techniques and the use of sophisticated ultrasound equipment, the partnership
      among fetal and paediatric cardiologists and a team of professionals working in
      Fetal Medicine Unit should not be ignored. As a result, targeted fetal
      echocardiography allows congenital heart disease to be diagnosed in utero with a
      great degree of accuracy from as early as the end of the first trimester of
      pregnancy i.e. from around 12 weeks. Conversely, prenatal detection rates in the
      general population remain suboptimal with many congenital cardiac abnormalities
      being diagnosed postnatally. A recognised marker for chromosomal abnormalities,
      that is the finding of an increased nuchal translucency thickness at 11-14 weeks
      of gestation has also emerged over the last few years as a novel and important
      marker for major cardiac abnormalities. This has further increased the interest
      in imaging the fetal heart early in the pregnancy.

PMID- 15986008
TI  - Tako-tsubo-like left ventricular dysfunction: clinical presentation, instrumental
      findings, additional cardiac and non-cardiac diseases and potential
      pathomechanisms.
AB  - Tako-tsubo-like left ventricular dysfunction phenomenon (TTP) has primarily been
      described in Japan and is characterized by transient left ventricular apical
      ballooning in the absence of coronary artery disease, associated with chest
      symptoms, electrocardiographic changes and minimal cardiac enzymes release. Aim
      of the present review is to summarize the current knowledge about TTP. TTP has
      been described predominantly in females. TTP occurs also outside Japan. Clinical
      symptoms comprise anginal chest pain, dyspnea and syncope. TTP occurs frequently
      after acute emotional or physical stress. Electrocardiographic ST- elevations may
      be present only for several hours. Then, normalization of the ST-segment occurs,
      followed by negative T waves, which persist for months. Arterial hypertension in
      TTP is found in up to 76%, hyperlipidaemia in up to 57%, diabetes mellitus in up
      to 12% and smoking in up to 18% of the patients. Several pathomechanisms have
      been proposed: myocardial stunning due to increased catecholamine levels,
      coronary vasospasm, atherosclerotic plaques rupture, myocarditis, catecholamine
      induced hyperkinesis of the basal left ventricular segments and genetic. Patients
      with TTP should be monitored like patients with myocardial infarction. Care
      should be taken in the application of catecholamines and nitrates. Betablockers
      should be given in the acute and chronic phase, and possibly indefinitely to
      prevent recurrences. The prognosis of TTP is assumed to be good, but in the acute
      phase there are deaths due to multisystem organ failure, cardiogenic shock,
      ventricular fibrillation and ventricular rupture. The long term prognosis of TTP
      patients is largely unknown.

PMID- 15986009
TI  - Surgical revascularization in the ischemic heart disease. Long-term results in a
      series of consecutive patients selected according to the principles.
AB  - AIM: Ischemic heart disease can be treated with drugs, percutaneous coronary
      interventions (PCI) and surgical revascularization (CABG). In our institution the
      therapeutic decisions for non emergent cases have been regularly taken during a
      daily meeting attended by clinicians, interventionalists, and surgeons, who all
      adhere to the principles of Evidence Based Medicine. The purpose of the present
      report is to investigate the long-term results in a series of consecutive
      patients to whom surgical revascularization has been recommended following the
      abovementioned approach. METHODS: We selected 597 patients with no prior
      interventions, who were referred to our institution for coronary angiography
      between January 1991 and December 1997 and to whom surgical revascularization was
      recommended. The Kaplan-Meier method was adopted to evaluate survival and freedom
      from: non fatal acute myocardial infarction, PCI, repeat CABG. RESULTS: The
      results were compared to those of the randomized trials or of large follow-up
      reports. The mean observation period was 6.8 years. The results at 5 and 10 years
      were: overall survival 95.5% and 90.2%; freedom from acute myocardial infarction
      95.5% and 90.2%; freedom from surgical reintervention 98.6% and 97.1%; freedom
      from PCI 91.2% and 79.8%; survival free from all events 79.3% and 58.1%. These
      rates were comparable to those reported by the most important clinical trials.
      CONCLUSIONS: If surgical treatment for patient with coronary artery disease is
      recommended according to the suggestions of the leading clinical trials and
      pertinent guidelines, the results in terms of mortality and morbidity are
      comparable to those of the trials themselves, even in the non selected patients
      of daily clinical practice.

PMID- 15986010
TI  - Highly active antiretroviral therapy in HIV-associated pulmonary hypertension.

PMID- 15986011
TI  - Acute posterior myocardial infarction in a 16-year-old heart transplant
      recipient.

PMID- 15986013
TI  - Immunosuppressive treatment options in renal transplantation.
AB  - An overview of the first 4 decades of clinical kidney transplantation would
      characterize progress primarily in the development of new immunosuppressive
      agents designed to reduce the incidence and severity of acute rejection to
      improve short-term outcomes, but with less marked effects on long-term patient
      and graft survival. The new trend of immunosuppressive therapy is to facilitate
      long-term allograft and patient survival, and to help to maintain a good quality
      of life after renal transplantation. To achieve these goals, transplant
      physicians need to determine the immunosuppressive protocols that will best
      minimize risk factors associated with reduced allograft/patient survival and
      quality of life. Recent protocols and clinical experience with modern
      immunosuppression strategies, as well as the efficacy and safety of various
      combination protocols, will be reviewed.

PMID- 15986012
TI  - Novel combinations in the treatment of hypertension.
AB  - Not uncommonly the effective treatment of hypertension requires multi-drug
      therapy. Multi-drug combinations that dominate clinical practice typically
      include a thiazide-type diuretic together with either an angiotensin-converting
      enzyme inhibitor, or an angiotensin-receptor blocker, or a beta-blocker. On the
      other hand, there are several medication choices that provide incremental blood
      pressure reduction but all too often go under-appreciated as to their
      effectiveness. Such drug combinations include within class switching of
      diuretics, combining a thiazide-type diuretic with a calcium-channel blocker,
      utilizing 2 calcium-channel blockers from different classes, giving an ACE
      inhibitor together with an angiotensin-receptor blocker, adding an aldosterone
      receptor antagonist to any of several other drug classes, as well as adding
      nitrate therapy to any of several other drug classes. Such novel pharmacologic
      approaches offer useful options for treatment in the otherwise difficult to
      control hypertensive patient.

PMID- 15986015
TI  - Ultrafiltration failure in peritoneal dialysis. Causes and clinical consequences.
AB  - Ultrafiltration failure (UFF) is the insufficient ability to remove excess fluid
      from the body by dialysis. In peritoneal dialysis (PD) this is a common
      complication, the frequency increases with duration of treatment. In this review
      a summary of peritoneal transport mechanisms and the conditions associated with
      UFF are discussed. The 2 most common circumstances in which ultrafiltration
      failure occurs, peritonitis and long-term PD treatment, are outlined more
      extensively. In addition a diagnostic approach and therapeutic options for the
      different causes of UFF are given.

PMID- 15986014
TI  - Vascular access complications in daily dialysis: a systematic review of the
      literature.
AB  - Patients treated for end stage renal disease (ESRD) have a shorter life
      expectancy and a poorer quality of life than the general population. In an
      attempt to improve outcomes for this patient population, a few novel therapeutic
      approaches have been undertaken. With hemodialysis, an increase in dialysis
      frequency and/or time has been associated with improvements in anemia, left
      ventricular hypertrophy, hypertension, hyperphosphatemia, nutrition and quality
      of life. Yet, access to these promising hemodialysis modalities has remained
      limited. The reasons for this are numerous, but one concern is the potential for
      more frequent vascular access complications with the increased frequency of
      cannulation for an arteriovenous fistula/graft and connection for a central
      venous catheter. In this systematic review of the literature, we identified all
      published studies that included 10 or more patients on daily hemodialysis and
      reported quantitative data pertaining to vascular access complications. Twelve
      studies met our inclusion criteria. The overall complication rates associated
      with vascular access do not appear to be increased and are perhaps even decreased
      with daily compared to conventional thrice-weekly hemodialysis. Arteriovenous
      fistulas are the vascular access of choice for daily hemodialysis; however, a non
      statistically significant increased complication rate for these accesses was
      reported in 2 North American studies. The reasons for this are unclear and
      require further research.

PMID- 15986016
TI  - Hepatitis C virus in chronic dialysis patients.
AB  - Since the cloning of hepatitis C virus (HCV), numerous serologic and virologic
      tests for detecting HCV infection have been developed and implemented in clinical
      practice. As a result, significant advances have been made in the study of HCV
      infection in patients with end-stage kidney disease. Patients on hemodialysis
      have a higher incidence and prevalence of HCV infection than the general
      population. In addition, HCV infection affects adversely survival among patients
      with end-stage kidney disease. Risk factors for HCV infection in dialysis
      patients include number of blood transfusions, duration of hemodialysis, mode of
      dialysis, prevalence of HCV infection in the dialysis unit, previous organ
      transplantation, intravenous drug use, male gender, older age and nosocomial
      transmission of HCV in hemodialysis units that can occur due to breakdown in
      standard infection control practices, physical proximity to an infected patient,
      cross-infection through dialysis machines, disrupted integrity of dialyzer
      membrane or dialyzer reprocessing. Suggested strategies to control HCV
      transmission in hemodialysis units include strict adherence to universal
      precautions, careful attention to hygiene, sterilization of dialysis machines and
      routine serologic testing and surveillance for HCV infection. Antiviral therapy
      with interferon alpha is recommended for selected categories of HCV-infected
      hemodialysis patients and kidney transplant candidates.

PMID- 15986017
TI  - The treatment of infections in dialysis.
AB  - Infectious complications are the leading cause of morbidity and mortality in
      peritoneal dialysis (PD) patients. Infectious diseases play a role in the
      morbidity and mortality of hemodialysis (HD) patients as well. Prevention of
      transmission of infectious diseases is of paramount importance in any program
      concentrating on renal replacement therapy, including HD, PD and kidney
      transplantation. Despite effective means to eradicate infections, increased usage
      of antimicrobial agents has resulted in antimicrobial resistance. The focus of
      this paper will be infections in dialysis. Some of the infectious complications
      discussed here may be applicable to patients with end-stage renal disease who
      have received a kidney transplant. Prevention of infections in dialysis includes
      development of infection control strategies by dialysis units with appropriate
      surveillance strategies. Dialysis staff education, patient education and
      physician participation is essential for successful infection control in dialysis
      units. Patients with other chronic infections, such as hepatitis B and human
      immunodeficiency virus (HIV) infection on dialysis may require additional
      infection control strategies for dialysis units to prevent infection of other
      patients and dialysis unit staff. Surveillance and prevention of tuberculosis is
      part of the comprehensive infection control plan for patients and staff and
      special considerations may occur for treatment of tuberculosis in other
      epidemiologic and economic areas of the world. Immunizations, a cornerstone to
      prevent many infections, have led to decreased morbidity and mortality for many
      diseases and many immunizations play a role in prevention of disease in dialysis
      patients.

PMID- 15986018
TI  - Diagnosis and treatment of primary glomerular diseases. Membranous nephropathy,
      focal segmental glomerulosclerosis and IgA nephropathy.
AB  - Membranous nephropathy, focal segmental glomerulosclerosis (FSGS) and IgA
      nephropathy are the most frequent and important primary glomerulopathies.
      Idiopathic membranous nephropathy and primary FSGS usually present with a
      nephrotic syndrome with or without renal insufficiency, whereas IgA nephropathy
      is more often characterized by (symptomless) hematuria and proteinuria. Although
      the outcome of these glomerulopathies is quite variable, many patients will
      progress to end-stage renal disease. In this review we discuss several aspects of
      the primary glomerulopathies with emphasis on the potential benefit of specific
      immunosuppressive regimens.

PMID- 15986023
TI  - On Chicken Little and the avian influenza.

PMID- 15986024
TI  - Regional medical services following a large earthquake: proposals by doctors.

PMID- 15986025
TI  - Pandemic influenza: are we ready?
AB  - An influenza pandemic is inevitable, and the H5N1 avian influenza outbreak in
      Southeast Asia has heightened concern that a disaster is imminent. Pandemic
      preparations are beginning around the world, and it is important for first
      responders, particularly disaster management personnel, to understand the
      difference between pandemic and epidemic influenza preparedness. This article
      will focus on distinguishing between an influenza epidemic and an influenza
      pandemic and, in light of these distinctions, how to manage the next pandemic
      with limited resources, particularly the absence of vaccine.

PMID- 15986026
TI  - Evacuation of a rural community hospital: lessons learned from an unplanned
      event.
AB  - A credible bomb threat forced the complete evacuation of a rural community
      hospital. An Incident Command System was implemented, and all 46 patients were
      temporarily transported and maintained at 2 local sites. They were returned to
      the hospital approximately 24 hours later. Only one patient experienced a
      complication possibly associated with the evacuation. This article discusses
      pertinent strategies and considerations involved in the planning and execution of
      a rural hospital evacuation. It further highlights the role of the emergency
      department medical and nursing staff throughout the evacuation process.

PMID- 15986027
TI  - Syndromic surveillance: hospital emergency department participation during the
      Kentucky Derby Festival.
AB  - INTRODUCTION: Electronic syndromic surveillance may have value in detecting
      emerging pathogens or a biological weapons release. Hospitals that have an agile
      process to evaluate chief complaints of patients seeking emergency care may be
      able to more quickly identify subtle changes in the community's health. An easily
      adaptable prototype system was developed to monitor emergency department patient
      visits during the Kentucky Derby Festival in Louisville, Kentucky, from April 16
      May 14, 2002. Use of the system was continued during the same festival periods in
      2003 and 2004. METHOD: Twelve area hospitals in Louisville, Kentucky,
      participated in a prospective analysis of the chief symptoms of patients who
      sought care in the emergency department during the Kentucky Derby Festival during
      2002. Six hospitals were classified as computer record groups (CRG) and used
      their existing computerized record capabilities. The other 6 hospitals used a
      personal digital assistant (PDA) with customized software (PDA group). Data were
      evaluated by the health department epidemiologist using SaTScan, a modified
      version of a cancer cluster detection program, to look for clusters of cases
      above baseline over time and by Zip code. RESULTS: All 12 hospitals were able to
      collect and provide data elements during the study period. The 6 CRG hospitals
      were able to perform daily data transmission; however, 3 CRG hospitals were
      unable to interpret their data because it was transmitted in pure text format. In
      contrast, data from all 6 PDA group hospitals were interpretable. Real-time data
      analysis was compared with post-event data, and it was found that the real-time
      evaluation correctly identified no unusual disease activity during the study
      period. CONCLUSIONS: The 12 hospitals participating in this study demonstrated
      that community-wide surveillance using computerized data was possible and that
      the 6 study hospitals using a PDA could quickly interpret emergency department
      patients' chief complaints. The emergency department chief complaints group could
      serve as a disease sentinel for the community.

PMID- 15986028
TI  - Nursing students' perceptions about disaster nursing.
AB  - Man-made or natural disasters are occurring more frequently in the United States
      and around the world. It is important that all nurses in all specialties be
      prepared to care for people affected by disasters. This article reports a
      descriptive study that sought to explore nursing students' perceptions about
      disaster nursing and to use the findings to suggest recommendations for building
      the discipline of disaster nursing. Results of this study indicate that nursing
      students had the following gaps of knowledge regarding disaster nursing: (1) an
      incomplete definition of disaster nursing; (2) lack of recognition about the
      importance of knowing community resources, having mock disaster drills, and
      utilizing disaster planning models; and (3) lack of perception that all nurses
      could play a significant role in disaster situations. The authors recommend that
      disaster nursing be taught by nursing faculty as a specialty in nursing programs.

PMID- 15986029
TI  - Patient safety tools: SARS, smallpox, monkeypox, and avian flu.

PMID- 15986032
TI  - A randomised controlled trial of nurse-managed trial conclusion following early
      phase cancer trial participation.
AB  - The effect of a nurse-managed intervention, for early phase cancer trial
      participants at trial conclusion, on psychosocial outcomes was evaluated at two
      cancer centres in the Midlands, England using a randomised controlled trial. It
      involved 117 patients who were participating in an early phase cancer clinical
      trial. It was a nurse-managed trial exit, which included a trial exit interview,
      trial feedback information leaflet and telephone follow-up compared with standard
      care at trial conclusion. Psychological distress at 1 week and 4-6 weeks post
      trial conclusion, patient's knowledge and understanding and patient's
      satisfaction were assessed. The results showed there was no significant
      difference between the two groups regarding scores for anxiety and depression at
      time one and time two. There is some suggestion that the intervention reduced
      anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt
      they had contributed to cancer research through trial participation. However,
      intervention patients were more likely to feel that they knew how the trial was
      going (P<0.001), knew how other people in the trial were doing (P=0.001), had all
      the feedback they needed about the trial they took part in (P<0.01) and knew how
      they would be followed up (P=0.02). Patient satisfaction with the intervention
      was high (median score=4.5 where 5 is greatest satisfaction). In conclusion,
      nurse-managed trial conclusion led to positive outcomes for patients who had
      recently completed a clinical trial.

PMID- 15986031
TI  - T-cell responses to human papillomavirus type 16 among women with different
      grades of cervical neoplasia.
AB  - Infection with high-risk genital human papillomavirus (HPV) types is a major risk
      factor for the development of cervical intraepithelial neoplasia (CIN) and
      invasive cervical carcinoma. The design of effective immunotherapies requires a
      greater understanding of how HPV-specific T-cell responses are involved in
      disease clearance and/or progression. Here, we have investigated T-cell responses
      to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical
      carcinoma directly ex vivo. T-cell responses were observed in the majority (78%)
      of samples. The frequency of CD4+ responders was far lower among those with
      progressive disease, indicating that the CD4+ T-cell response might be important
      in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease
      grades, inferring that E6-specific CD8+ T cells are not vitally involved in
      disease clearance. T-cell responses were demonstrated in the majority (80%) of
      cervical cancer patients, but are obviously ineffective. Our study reveals
      significant differences in HPV16 immunity during progressive CIN. We conclude
      that the HPV-specific CD4+ T-cell response should be an important consideration
      in immunotherapy design, which should aim to target preinvasive disease.

PMID- 15986033
TI  - Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic
      support in advanced pancreatic adenocarcinoma.
AB  - This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate
      (FDR) of gemcitabine (2'-2'-difluorodeoxycitidine) infusion with circulating
      haemopoietic progenitor support and to evaluate the activity of the treatment.
      Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina
      (dFdU) measured at first course and the activity andexpression profile of
      cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced
      pancreatic carcinoma received escalating dose of gemcitabine 10 mg m(-2) min(-1)
      every 2 weeks with circulating haemopoietic progenitor support. First dose level
      was 3000 mg m(-2) and the doses were increased by 500 mg m(-2) until MTD. In all,
      23 patients were enrolled. Toxicities were mild or moderate; the only patient
      treated at 7000 mg m(-2) died because of toxicity; therefore; the MTD was
      established at 6500 mg m(-2). The overall response rate was 22.2%. The AUC of
      gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a
      plateau at 4500 mg m(-2). A significant relationship was found between the AUC of
      dFdU and CdA expression and activity (P<0.05). Moreover, progression rate and
      survival were significantly related to CdA expression and activity levels. The
      activity of high-dose gemcitabine is not superior to that reported with less
      intensive FDR schedules. The predictive role of CdA expression and activity on
      outcome deserves further investigation.

PMID- 15986034
TI  - A phase I clinical trial of continual alternating etoposide and topotecan in
      refractory solid tumours.
AB  - The goal of this phase I study was to develop a novel schedule using oral
      etoposide and infusional topotecan as a continually alternating schedule with
      potentially optimal reciprocal induction of the nontarget topoisomerase. The
      initial etoposide dose was 15 mg m(-2) b.i.d. days (D)1-5 weeks 1,3,5,7,9 and 11,
      escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12
      was administered by 96 h infusion at an initial dose of 0.2 mg m(-2) day(-1) with
      a dose escalation of 0.1, then at 0.05 mg m(-2) day(-1). Eligibility criteria
      required no organ dysfunction. Two dose reductions or delays were allowed. A
      total of 36 patients with a median age of 57 (22-78) years, received a median 8
      (2-19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of
      grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line
      related thrombosis or infection and one subsequently developed AML. There was no
      febrile neutropenia. There were six radiologically confirmed responses (18%) and
      56% of patients demonstrated a response or stable disease, typically with only
      modest toxicity. Oral etoposide 35 mg m(-2) b.i.d. D1-5 and 1.8 mg m(-2) 96 h
      (total dose) infusional topotecan D8-11 can be administered on an alternating
      continual weekly schedule for at least 12 weeks, with promising clinical
      activity.

PMID- 15986035
TI  - mRNA quantification and clinical evaluation of telomerase reverse transcriptase
      subunit (hTERT) in intracranial tumours of patients in the island of Crete.
AB  - Telomerase is a reverse transcriptase that maintains telomeres by adding
      telomeric TTAGGG repeats to the ends of human chromosomes. The aim of this study
      was to evaluate quantitatively the mRNA expression of telomerase catalytic
      subunit (hTERT) in different types of intracranial tumours in relation to their
      histologic pattern and grade and correlate it with progression-free (PFS) and
      overall survival (OS) of patients. Human telomerase reverse transcriptase mRNA
      levels were estimated by the use of real time RT-PCR in 68 samples of
      intracranial tumours. It revealed statistical correlation between hTERT mRNA
      expression levels and the grade of the tumours (P<0.001). Patients having
      negative expression of hTERT mRNA had statistically longer PFS (P=0.031) and OS
      (P=0.047). Cox univariate regression analysis revealed that hTERT mRNA-positive
      patients had a high and statistically significant risk of relapse (hazard ratio
      (HR) of 2.24 and P=0.038). In the Cox multivariate regression model, the levels
      of hTERT mRNA were adjusted for tumour grade and patients age, and since there
      was statistically significant relationship between the levels of hTERT mRNA and
      the grade of the tumours (P=0.003 or P=0.006, respectively), hTERT mRNA levels
      could not be considered as an independent prognostic factor for PFS or OS.

PMID- 15986036
TI  - Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic
      cancer: a randomised phase II trial of the Italian oncology group for clinical
      research (GOIRC).
AB  - This study was performed to determine the activity of adding continuous infusion
      (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced
      pancreatic cancer (APC). In all, 94 chemo-naive patients with APC were randomised
      to receive GEM alone (arm A: 1000 mg m(-2) per week for 7 weeks followed by a 2
      week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in
      combination with CI 5-FU (arm B: CI 5-FU 200 mg m(-2) day(-1) for 6 weeks
      followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall
      response rate (RR) was the primary end point and criteria for decision were
      planned according to the Simon's optimal two-stage design. The overall RR was 8%
      (arm A) and 11% (arm B) (95% confidence interval: 0.5-16% and 2-22%),
      respectively, and stable disease was 29 and 28%. The median duration of RR was 34
      weeks (range 25-101 weeks) for GEM and 26 weeks (range 16-46 weeks) for the
      combination. The median progression-free survival (PFS) was 14 weeks (range 2-65
      weeks) and 18 weeks (range 4-51 weeks), respectively. The median overall survival
      (OS) was 31 weeks (range 1-101 weeks) and 30 weeks (1-101 weeks). Toxicity was
      mild in both arms. This study does not show promising activity in terms of RR,
      PFS and OS for the double combination arm in APC.

PMID- 15986037
TI  - Diffuse EGFR staining is associated with reduced overall survival in locally
      advanced oesophageal squamous cell cancer.
AB  - Squamous cell carcinoma of the oesophagus (SCCO) is still a pathology of bad
      prognosis. Specific therapies are now developed against epidermal growth factor
      receptor (EGFR), human epidermal growth factor receptor 2, c-kit receptor
      (CD117), vascular endothelial growth factor (VEGF) and p53 protein. This study
      was aimed at assessing their expression in a large series of SCCO, as well as
      their potential therapeutic interest in this pathology. Immunohistochemical
      expression of these factors was assessed retrospectively in 107 cases of SCCO
      with primary surgery, as well as their relationships to recurrence, metastasis
      and overall survival on a long-term follow-up. Human epidermal growth factor
      receptor 2 and CD117 were expressed in less than 3% of the cases. Epidermal
      growth factor receptor and p53 were overexpressed in 68.2 and 66.4% of the cases,
      and VEGF in 38.3%. Epidermal growth factor receptor overexpression was
      significantly related to vascular invasion (P=0.023). Its diffuse positivity was
      significantly related in multivariate analysis to higher local recurrence
      (P=0.006) and lower overall survival (P=0.003), in a subgroup of patients of poor
      outcome who had received postoperative adjuvant treatment. These results
      highlight the great potential prognostic and therapeutic interest of evaluating
      EGFR diffuse positivity in locally advanced SCCO.

PMID- 15986038
TI  - Polymorphism at 3' UTR +28 of the prion-like protein gene is associated with
      sporadic Creutzfeldt-Jakob disease.
AB  - The downstream prion-like protein (doppel or Dpl) shares significant biochemical
      and structural homology with the cellular prion protein, PrP(C), which is
      considered as a responsible protein for the transmissible spongiform
      encephalopathies (TSEs) or prion diseases. Recently, polymorphisms in open
      reading frame (ORF) of the prion-like protein gene (PRND) have been analysed in
      relation to the occurrence of prion diseases and other neurodegenerative
      disorders. We examined the role of a single-nucleotide polymorphism (SNP) at 3'
      untranslated region (UTR) +28 of PRND. We analysed this polymorphism in 110
      Korean patients with sporadic Creutzfeldt-Jakob disease (CJD) and 102 healthy
      control subjects. Significant differences in genotype (P=0.005) and allele
      (P=0.032) frequencies at 3' UTR +28 were observed between sporadic CJD and normal
      controls. This result suggests that the PRND polymorphism at 3' UTR +28 might be
      associated with the occurrence of sporadic CJD.

PMID- 15986039
TI  - Potential harms, anonymization, and the right to withdraw consent to biobank
      research.
AB  - This paper discusses the potential harms involved in biobank research and how
      ethical review, informed consent, withdrawals, and anonymization of samples
      should be handled in the light of these harms. There is less risk involved in
      biobank research than in human subject research; it should therefore be treated
      differently. In our view, anonymization should not be an automatically
      permissible response to requests for withdrawal. Nor should a request for
      withdrawal necessarily stop research on identifiable samples. Apart from not
      being particularly appropriate for protecting the interests of individuals,
      anonymization of samples has a negative impact on research. We suggest that the
      current view on withdrawal from research, supported by the Declaration of
      Helsinki and subsequent ethical guidelines, be abandoned in the context of
      biobank research and be replaced by an approach inspired by the Nuremberg Code.
      This approach requires those wishing to withdraw their samples from research to
      present sufficient reason for doing so. Our interpretation of 'sufficient reason'
      includes all those involving genuine, deeply felt concerns that are not based on
      misconceptions. Still, this underlines the fact that we all share a
      responsibility for health research and that no one should take withdrawal from
      biobank research lightly.

PMID- 15986040
TI  - Ultraconserved regions in multiple sclerosis.

PMID- 15986041
TI  - Molecular characterisation of patients with subtelomeric 22q abnormalities using
      chromosome specific array-based comparative genomic hybridisation.
AB  - The 22q13 deletion syndrome is associated with global developmental delay, absent
      or delayed speech, and generalised hypotonia. In this study, the size and nature
      of 22q13 deletions (n=9) were studied in detail by high-resolution chromosome
      specific array-based comparative genomic hybridisation (array CGH). The deletion
      sizes varied considerably between the different patients, that is, the largest
      deletion spanning 8.4 Mb with the breakpoint mapping to 22q13.2 and the smallest
      deletion spanning 3.3 Mb with the breakpoint mapping to 22q13.31. In one case, a
      unique subtelomeric 3.9 Mb deletion associated with a 2.0 Mb duplication of 22q13
      was observed, adding to a growing number of similar cases identified for other
      chromosome ends. Remarkably, this patient had signs suggestive of retinitis
      pigmentosa, which has never been reported before in the 22q13 deletion syndrome.
      The identification of two pairs of recurrent proximal breakpoints on 22q13
      suggests that these specific regions may be prone to recombination, due to yet
      unknown genome architectural features. In addition to the copy number changes on
      22q13, a duplication of approximately 330 kb on 22q11.1 was observed and shown to
      be a genetic large-scale copy number variation without clinical consequences. The
      current study failed to reveal relationships between the clinical features and
      the deletion sizes. Global developmental delay and absent or severely delayed
      speech were observed in all patients, whereas hypotonia was present in 89% of the
      cases (8/9). This study underscores the utility of array CGH for characterising
      the size and nature of subtelomeric deletions, such as monosomy 22q13, and
      underlines the considerable variability in deletion size in the 22q13 deletion
      syndrome regardless of the clinical phenotype.

PMID- 15986044
TI  - River water quality and pollution sources in the Pearl River Delta, China.
AB  - Some physicochemical parameters were determined for thirty field water samples
      collected from different water channels in the Pearl River Delta Economic Zone
      river system. The analytical results were compared with the environmental quality
      standards for surface water. Using the SPSS software, statistical analyses were
      performed to determine the main pollutants of the river water. The main purpose
      of the present research is to investigate the river water quality and to
      determine the main pollutants and pollution sources. Furthermore, the research
      provides some approaches for protecting and improving river water quality. The
      results indicate that the predominant pollutants are ammonium, phosphorus, and
      organic compounds. The wastewater discharged from households in urban and rural
      areas, industrial facilities, and non-point sources from agricultural areas are
      the main sources of pollution in river water in the Pearl River Delta Economic
      Zone.

PMID- 15986045
TI  - Use of PFU protozoan community structural and functional characteristics in
      assessment of water quality in a large, highly polluted freshwater lake in China.
AB  - Structural and functional parameters of protozoan communities colonizing on PFU
      (polyurethane foam unit) artificial substrate were assessed as indicators of
      water quality in the Chaohu Lake, a large, shallow and highly polluted freshwater
      lake in China. Protozoan communities were sampled 1, 3, 6, 9 and 14 days after
      exposure of PFU artificial substrate in the lake during October 2003. Four study
      stations with the different water quality gradient changes along the lake were
      distinguishable in terms of differences in the community's structural (species
      richness, individual abundance, etc.) and functional parameters (protozoan
      colonization rates on PFU). The concentrations of TP, TN, COD and BOD as the main
      chemical indicators of pollution at the four sampling sites were also obtained
      each year during 2002-2003 for comparison with biological parameters. The results
      showed that the species richness and PFU colonization rate decreased as pollution
      intensity increased and that the Margalef diversity index values calculated at
      four sampling sites also related to water quality. The three functional
      parameters based on the PFU colonization process, that is, S(eq), G and T90%,
      were strongly related to the pollution status of the water. The number of
      protozoan species colonizing on PFU after exposure of 1 to 3 days was found to
      give a clear comparative indication of the water quality at the four sampling
      stations. The research provides further evidence that the protozoan community may
      be utilized effectively in the assessment of water quality and that the PFU
      method furnishes rapid, cost-effective and reliable information that may be
      useful for measuring responses to pollution stress in aquatic ecosystems.

PMID- 15986046
TI  - On-filter determination of collected wood dust by diffuse reflectance infrared
      Fourier-transform spectroscopy (DRIFTS).
AB  - A new analytical technique based on DRIFTS spectroscopy has been developed for
      the specific and sensitive determination of size-fractionated wood dust from 37
      mm glass fiber filter samples collected with the Respicon sampler. A
      translational diffuse reflectance apparatus was modified to accept filter samples
      by incorporating a special filter holder in the sample stage and a clockwork
      motor to drive the translational stage during infrared scanning, thus providing
      an average analysis across the filter face. Filter samples were pre-treated with
      ethyl acetate to uniformly redeposit dust onto the filter and extract potential
      chemical interferences. Two absorbance maxima (1251 and 1291 cm(-1)),
      corresponding to the cellulose content of the wood, were suitable for
      quantitation of wood dust. Analysis of seven species of wood at 1291 cm(-1)
      showed an equivalent quantitative response for all species except maple. The
      response at 1251 cm(-1) was more variable across species but more sensitive for
      the softwoods. There was a statistically significant effect of particle size on
      the analytical response, so that analytical standards should be matched to the
      samples in terms of particle size distribution. Analytical limit of detection was
      approximately 0.08 mg of wood dust per sample with overall precision of about 6%.
      Comparison of DRIFTS and gravimetric analyses of 51 pure wood dust samples
      ranging from about 0.2 to 2 mg yielded a slope of 1.08 and r2 equal to 0.9. Other
      particulate contaminants common in the industrial wood processing industry showed
      little or no interference with the determination of wood dust by this method.

PMID- 15986047
TI  - Near-real-time determination of hydrogen peroxide generated from cigarette smoke.
AB  - The ability to monitor hydrogen peroxide (H2O2) in aqueous smoke extracts will
      advance our understanding of the relationship between cigarette smoke-induced
      oxidative stress, inflammation, and disease and help elucidate the pathways by
      which the various smoke constituents exert their pathogenic effects. We have
      demonstrated, for the first time, the measurement of H2O2 production from
      cigarette smoke without prior separation of the sample. Cigarettes were tested on
      a commercial smoking machine, such that the whole smoke or gas vapor phase was
      bubbled through phosphate buffered saline solution at pH 7.4. Aliquots of these
      solutions were analyzed using an Amplex Red/horseradish peroxidase fluorimetric
      assay that required only a 2 minute incubation time, facilitating the rapid,
      facile collection of data. Catalase was used to demonstrate the selectivity and
      specificity of the assay for H2O2 in the complex smoke matrix. We measured
      approximately 7-8 microM H2O2 from two reference cigarettes (i.e., 1R4F and
      2R4F). We also observed 9x more H2O2 from whole smoke bubbled samples compared to
      the gas vapor phase, indicating that the major constituent(s) responsible for
      H2O2 formation reside in the particulate phase of cigarette smoke. Aqueous
      solutions of hydroquinone and catechol, both of which are particulate phase
      constituents of cigarette smoke, generated no H2O2 even though they are free
      radical precursors involved in the production of reactive oxygen species in the
      smoke matrix.

PMID- 15986048
TI  - Thio arsenosugars in freshwater mussels from the Danube in Hungary.
AB  - In contrast to the large body of data on naturally-occurring arsenic compounds in
      marine organisms, relatively little is known about arsenic speciation in
      freshwater biota. We report an investigation using HPLC-ICPMS into the arsenic
      compounds in five species of freshwater mussels collected from five sites from
      the Danube in Hungary. Total arsenic concentrations in the mussels ranged from
      3.8-12.8 mg As kg(-1). The arsenic speciation patterns were broadly similar for
      mussels representing each of the five species and five sites, but quite different
      from those reported for marine mussels. The major extractable arsenicals were two
      oxo arsenosugars (glycerol sugar and phosphate sugar), and their thio analogues
      (thio glycerol sugar and thio phosphate sugar). Arsenobetaine, usually the major
      arsenical in marine organisms, was not a significant compound in the freshwater
      mussels and was detected in only three of the 11 samples. This is the first
      report of thio arsenosugars in freshwater biota and suggests that these compounds
      may be common and widespread naturally-occurring arsenicals.

PMID- 15986049
TI  - Determination of metal and organometal trophic bioaccumulation in the benthic
      macrofauna of the Adour estuary coastal zone (SW France, Bay of Biscay).
AB  - A multidisciplinary approach has been adopted in order to investigate the
      bioaccumulation of metals and organometals in macrobenthic populations. A
      complete method coupling a sampling strategy and classification of benthic
      organisms with a performant analytical procedure for the analysis of both metals
      and organometals has been developed. A single sample preparation method using a
      TMAH extraction and species specific isotope dilution makes it possible to
      analyse metals and organometals in the same extract, which is especially
      interesting for situations where only a limited amount of sample is available.
      Low detection limits have been obtained in the range of 12-250 pg g(-1) for
      mercury and butyltin compounds and 0.4-50 ng g(-1) for metals with good precision
      (1-10% RSD) even for a very low mass of sample (0.02 g). This method has been
      applied for monitoring contamination and bioaccumulation of metals and
      organometals as well as the biodiversity and trophic structure of the
      macrobenthic population of the Adour Estuary (South-West, France). The benthic
      macrofauna diversity indicates that inner estuarine stations are moderately
      polluted whereas outer estuarine stations are less impacted. However, metals
      concentrations in both sediment and benthic biomass do not change drastically
      between stations. Moreover, the bioaccumulation has been determined in relation
      to the feeding guild of benthic organisms. The results demonstrate that higher
      bioaccumulation is generally observed for deposit feeders directly impacted by
      sediment contamination compared to suspensive feeders and predators.
      Biomagnification along the trophic levels was highlighted for MMHg but no
      significant trend was observed for the other metallic compounds.

PMID- 15986050
TI  - Polychlorinated biphenyls in marine sediments from the southern North Sea and
      Scheldt estuary: a ten-year study of concentrations, patterns and trends.
AB  - The paper reports the concentrations and patterns of CBs in sediments of the
      Belgian part of the southern North Sea and the Scheldt estuary for the period
      1991-2001. The long-term analytical performance was well within the quality
      assurance boundaries set at the outset of the study and is consistent with the
      state of the art for this type of analysis. The CB concentrations (given as the
      median of the sum of IUPAC Nos 28, 52, 101, 118, 138, 153 and 180) vary between
      0.1 microg kg(-1) and 50 microg kg(-1) dry weight in the total sediment and it
      could be demonstrated that CB patterns in the fine fraction of the sediment were
      closely similar throughout the investigated area. Isolation of the fine fraction
      (<63 microm) by sieving can be regarded as a physical normalisation to reduce the
      differences in sediment granulometric composition. It allows for a better
      understanding of CB distribution and patterns and improves the trend analysis. A
      significant downward trend could not be found at any of the stations, which
      suggests that CB levels have not been changing in the area of interest in the
      past decade.

PMID- 15986051
TI  - An assessment of the bioavailability of persistent organic pollutants from
      contaminated soil.
AB  - A procedure to assess the bioavailability of persistent organic pollutants (POPs)
      from soil samples has been developed. The procedure is based on the use of
      simulated in vitro gastrointestinal extraction to remove POPs from soil matrices.
      The level of recovery, using this approach, is assessed following liquid-liquid
      extraction (LLE) and analysis by gas chromatography-mass selective detection (GC
      MSD). The remaining soil residue is then extracted using pressurised fluid
      extraction (PFE) followed by GC-MSD analysis to assess the residual fraction. The
      residual fraction is monitored to determine the unavailable fraction i.e. not
      available for absorption in the gastrointestinal tract of humans. The procedure
      was applied to four soil samples i.e. an aged, spiked soil and three certified
      reference materials (CRMs) contaminated with POPs. Recoveries of pesticides
      (lindane, endosulfan I, endrin, DDE, DDD and endosulfan II), phenols (cresol, TCP
      and PCP), and base neutral compounds (hexachloroethane, acenaphthene,
      dibenzofuran, fluorene and hexachlorobenzene) from aged, spiked soil following
      extraction with gastric fluid ranged from 0.8 to 8.3% while following intestinal
      extraction ranged from 5.5 to 13.5%, irrespective of POP. Recoveries of
      pesticides (lindane, endosulfan I, endrin, DDE, DDD and endosulfan II) from CRM
      805-050 following extraction with gastric fluid were below the limit of detection
      while following intestinal extraction ranged from 5.3 to 12.8%. Recoveries of
      phenols (cresol, TCP and PCP) from CRM 401-225 following extraction with gastric
      fluid ranged from 1.6 to 2.0% while following intestinal extraction ranged from
      4.1 to 5.4%. Recoveries of base neutral acid analytes (hexachloroethane,
      acenaphthene, dibenzofuran, fluorene and hexachlorobenzene) from CRM 107-100
      following extraction with gastric fluid ranged from 1.4 to 4.0% while following
      intestinal extraction ranged from 6.6 to 12.7%. It has been found that the
      majority of POPs present i.e. >75%, would be excreted if consumed and not be
      absorbed in the gastrointestinal tract of humans.

PMID- 15986052
TI  - A laboratory investigation of the effectiveness of various skin and surface
      decontaminants for aliphatic polyisocyanates.
AB  - Isocyanates may cause contact dermatitis and respiratory sensitization leading to
      asthma. Dermal exposure to aliphatic isocyanates in auto body shops is very
      common. However, little is known about the effectiveness of available commercial
      products used for decontaminating aliphatic polyisocyanates. This experimental
      study evaluated the decontamination effectiveness of aliphatic polyisocyanates
      for several skin and surface decontaminants available for use in the auto body
      industry. The efficiency of two major decontamination mechanisms, namely (i)
      consumption of free isocyanate groups via chemical reactions with active hydrogen
      components of the decontaminant and (ii) physical removal processes such as
      dissolution were studied separately for each decontaminant. Considerable
      differences were observed among surface decontaminants in their rate of
      isocyanate consumption, of which those containing free amine groups performed the
      best. Overall, Pine-Sol(R) MEA containing monoethanolamine was the most efficient
      surface decontaminant, operating primarily via chemical reaction with the
      isocyanate group. Polypropylene glycol (PPG) had the highest physical removal
      efficiency and the lowest reaction rate with isocyanates. All tested skin
      decontaminants performed similarly, accomplishing decontamination primarily via
      physical processes and removing 70-80% of isocyanates in one wiping. Limitations
      of these skin decontaminants are discussed and alternatives presented. In vitro
      testing using animal skins and in vivo testing with field workers are being
      conducted to further assess the efficiency and identify related determinants.

PMID- 15986053
TI  - Concentrations, sources and temporal trends in atmospheric polycyclic aromatic
      hydrocarbons in a major conurbation.
AB  - Concentrations of atmospheric PAH were separately determined in total suspended
      particulate matter and associated vapour phase in ambient air in Birmingham, UK.
      Samples of 24 h duration were taken simultaneously at two locations (the Bristol
      Road Observatory Site, BROS, and the Elms Road Observatory Site, EROS) on 44
      separate occasions every one to two weeks between October 1999 and January 2001.
      BROS was 10 m from the busy Bristol Road, 800 m from EROS that was located within
      the "green space" of the University of Birmingham campus. With the exception of
      acenaphthene, average concentrations of all measured PAH at BROS exceed those at
      EROS, with a paired t-test revealing these roadside increments to be significant
      (p < 0.05) for 9 out of the 16 target PAH, demonstrating the importance of
      traffic emissions of PAH. Although the declines were not statistically
      significant (p > 0.05) except for phenanthrene and fluoranthene, concentrations
      of individual PAH at EROS between July and December inclusive in 1999 and 2000
      fell by between 16 and 54% compared with those during the same months in 1997.
      Multiple linear regression of PAH concentrations against meteorological variables
      confirmed the influence of the Bristol Road on BROS but not EROS. Cluster
      analysis of PAH contamination in individual samples showed there to be two
      statistically distinct groups of samples. One group contained 15 samples, all of
      which displayed elevated concentrations. Examination of air mass back trajectory
      data, revealed that these PAH pollution episodes originate due to the combined
      effects of meteorology and local traffic emissions, rather than as a result of
      long-range transport. Eighteen 12 h samples were also taken at EROS over the
      period of the November Bonfire Night festivals of 1999 and 2000. These revealed
      significantly elevated PAH concentrations on the nights when ignition of bonfires
      and fireworks would be anticipated to peak. These results are relevant to
      assessments of the impact of similar "festivals of fire" elsewhere. In
      particular, retene (7-isopropyl-1-methylphenanthrene) concentrations were
      especially elevated, indicating it has possible utility as an indicator of wood
      combustion emissions.

PMID- 15986054
TI  - Mass, surface area and number metrics in diesel occupational exposure assessment.
AB  - While diesel aerosol exposure assessment has traditionally been based on the mass
      concentration metric, recent studies have suggested that particle number and
      surface area concentrations may be more health-relevant. In this study, we
      evaluated the exposures of three occupational groups-bus drivers, parking garage
      attendants, and bus mechanics-using the mass concentration of elemental carbon
      (EC) as well as surface area and number concentrations. These occupational groups
      are exposed to mixtures of diesel and gasoline exhaust on a regular basis in
      various ratios. The three groups had significantly different exposures to
      workshift TWA EC with the highest levels observed in the bus garage mechanics and
      the lowest levels in the parking ramp booth attendants. In terms of surface area,
      parking ramp attendants had significantly greater exposures than bus garage
      mechanics, who in turn had significantly greater exposures than bus drivers. In
      terms of number concentrations, the exposures of garage mechanics exceeded those
      of ramp booth attendants by a factor of 5-6. Depending on the exposure metric
      chosen, the three occupational groups had quite different exposure rankings. This
      illustrates the importance of the choice of exposure metric in epidemiological
      studies. If these three occupational groups were part of an epidemiological
      study, depending on the metric used, they may or may not be part of the same
      similarly exposed group (SEG). The exposure rankings (e.g., low, medium, or high)
      of the three groups also changes with the metric used. If the incorrect metric is
      used, significant misclassification errors may occur.

PMID- 15986055
TI  - Field test results of an automated exposure assessment tool, the local
      positioning system (LPS).
AB  - A user-friendly environmental monitoring system that collects real time data has
      been developed. Flash card memory logs exposure data from multiple sensors along
      with corresponding times and positions. Optional use of telemetry repeaters and a
      reference station allows central monitoring of data to assess exposure and to
      initiate intervention when safe levels are exceeded. A software analysis package
      allows researchers to identify exposure hot spots and direct control efforts,
      with the ultimate goal being to reduce injury and disease. Preliminary field test
      results document position accuracy and system performance in harsh environments.

PMID- 15986056
TI  - Spectroscopic study of ALA-induced endogenous porphyrins in arthritic knee
      tissues: targeting rheumatoid arthritis PDT.
AB  - The inflamed synovium of rheumatoid arthritis exhibits many features typical for
      neoplastic tissue implying that the photodynamic therapy might be an efficient
      modality for chronic poliarthritis. The accumulation of endogenously produced
      porphyrins after administration of exogenous 5-aminolevulinic acid (ALA) in a
      rabbit model of rheumatoid arthritis was evaluated by fluorescence spectroscopy.
      Independent of the way, intravenously or intra-articularly, in which ALA was
      administered to the experimental animals, the highest fluorescence intensity of
      endogenously produced porphyrins was detected in the tissues of the inflamed
      joints. Besides, the application of ALA had a systemic sensitising effect on the
      whole organism of rabbits. The highest amount of endogenously produced porphyrins
      in the inflamed joints measured from the surface of the skin above the synovium
      tissues was detected 1-3 h after the administration of ALA. Fluorescence
      measurements performed on the tissue specimens ex vivo showed the predominant
      accumulation of porphyrins in the synovium of the inflamed joints. The
      fluorescence of porphyrins was also observed in the cartilage tissues taken from
      knee joints. However, the fluorescence spectra features indicated that the
      composition of porphyrins detected in the cartilage tissues was different than
      that in the synovial tissues. The selective accumulation of porphyrins in the
      inflamed synovial tissues stands up for the application of photodynamic therapy
      in the treatment of rheumatoid arthritis and implies the possibility to use
      optical non-invasive methods based on fluorescence detection of endogenously
      produced porphyrins for diagnostics of inflamed tissues.

PMID- 15986057
TI  - Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice.
AB  - The rise of multiply antibiotic resistant bacteria has led to searches for novel
      antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a
      potential candidate; it uses the combination of a photosensitizer with visible
      light to produce reactive oxygen species that lead to cell death. We used PDT
      mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat
      burn wounds in mice with established Staphylococcus aureus infections The third
      degree burn wounds were infected with bioluminescent S. aureus. PDT was applied
      after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution
      to the wound followed by illumination with red light and periodic imaging of the
      mice using a sensitive camera to detect the bioluminescence. More than 98% of the
      bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of
      PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed
      the wound healing. These data suggest that PDT has the potential to rapidly
      reduce the bacterial load in infected burns. The treatment needs to be optimized
      to reduce wound damage and prevent recurrence.

PMID- 15986058
TI  - Photophysicochemical consequences of bovine serum albumin binding to non
      transition metal phthalocyanine sulfonates.
AB  - The interactions between bovine serum albumin (BSA) and sulfonated
      metallophthalocyanine (MPc) complexes of aluminum (AlPcS(mix)), zinc
      (ZnPcS(mix)), silicon (SiPcS(mix)), germanium (GePcS(mix)) and tin (SnPcS(mix))
      are studied using fluorescence quenching of BSA by MPc complexes. The
      fluorescence quantum yields of the non-aggregated MPc complexes (AlPcS(mix),
      GePcS(mix) and SiPcS(mix)) decreased in the presence of BSA, but increased for
      the aggregated ZnPcS(mix) and SnPcS(mix) complexes. The BSA: MPc conjugates were
      less stable than the corresponding MPc complexes. The quenching constants were
      much higher for the non-aggregated complexes. The aggregated nature of the
      complexes also affected the rate constants (k(F), k(IC), k(ISC)) for the
      deactivation of the excited singlet state.

PMID- 15986059
TI  - Suppression of contact hypersensitivity after repeated exposures of humans to low
      doses of solar simulated radiation.
AB  - Although it is generally recognised that UV radiation (UVR) can induce
      suppression of contact hypersensitivity (CHS) in human subjects, most protocols
      to date have not tested the effect of low daily doses of solar simulated
      radiation (SSR). In the present study, healthy individuals, divided into four
      groups each consisting of approximately 34 subjects, were whole-body irradiated
      with 1.2 standard erythema doses of SSR for 2, 10 or 30 consecutive days, or were
      unirradiated. They were sensitised with diphenylocyclopropenone (DPCP) on one
      exposed body site 24 h after the final UVR. The occurrence and severity of the
      primary allergic response were noted, and both parameters were shown to be
      significantly lowered in the group irradiated for 30 days compared with the
      unirradiated group. Elicitation of CHS was undertaken 3 weeks after the
      sensitisation, using a range of concentrations of DPCP on a UV-protected body
      site. The extent of the CHS at 48 h was assessed by the clinical score, by an
      erythema meter and by histological examination of a biopsy taken from the site
      challenged with one selected concentration of DPCP. Although erythema and
      pigmentation did not differ between the groups, a significant negative
      correlation was found between the clinical CHS score and the number of days of UV
      exposure, at the lowest challenge dose of DPCP. In addition a significant
      negative correlation was revealed between the intensity of spongiosis
      (intraepidermal oedema and vesicles, as evaluated by histology) and the number of
      days of UV exposure. Thus small daily doses of SSR induce suppression of CHS in
      human subjects and the effect is cumulative, indicating that there is no
      adaptation to the immunomodulating effects of UVR, at least over the test period
      of 30 days.

PMID- 15986060
TI  - Studies on curcumin and curcuminoids. XXIX. Photoinduced cytotoxicity of curcumin
      in selected aqueous preparations.
AB  - Natural curcumin was evaluated as a potential photosensitizer for oral
      applications. The photocytotoxicity of curcumin on salivary gland acinar cells
      (SM 10-12) was investigated in five aqueous preparations consisting of 5% DMSO,
      non-ionic micelles, cyclodextrin, liposomes, or a hydrophilic polymer. The
      difference in phototoxic effects between natural curcumin and synthetic curcumin
      was examined. Cytotoxicity in SM 10-12 cells exposed to curcumin in the
      concentration range 0.4-13.5 microM was investigated by MTT test, a fluorescence
      staining microscopic test, and by Western immunoblotting techniques. The
      potential formation of a photoreaction product, hydrogen peroxide, was evaluated
      by a fluorescence assay. The light source was a halogen lamp used in the dental
      clinic, emitting mainly in the blue part of the spectrum. The phototoxic effect
      on SM 10-12 cells was dependent on curcumin concentration, the light dose and the
      type of preparation. Natural and synthetic curcumin induced phototoxicity to the
      same extent. Significant effects on the cells were obtained at low curcumin
      concentrations (< or =0.5 microM) and at a low light dose (< or =6 J cm(-2)),
      after 3 h incubation. Neither the activation of caspases-3, -7, -8 or -9, nor the
      formation of hydrogen peroxide could be detected in cells exposed to curcumin and
      light. The liposome preparation was the most efficient vehicle for curcumin to
      induce cell death. The phototoxic effect induced by curcumin is highly dependent
      on the type of preparation. Curcumin might be a potential photosensitizer in the
      treatment of oral lesions and cancers provided careful selection of the vehicle.

PMID- 15986061
TI  - Action cross sections of two-photon excited luminescence of some Eu(III) and
      Tb(III) complexes.
AB  - Four different luminescent lanthanide complexes have been studied with respect to
      multiphoton excitation using near-infrared femtosecond pulses. The method for
      measuring action cross sections of two-photon excited fluorescence in solution
      relative to a known standard is reviewed. Two refractive index-related
      corrections are necessary in this method: one for the multiphoton excitation
      process, the other for the collection of the emitted light. It has been found
      that (2,4,6-trimethoxyphenyl)dipicolinic acid and Michler's ketone are reasonable
      sensitisers of two-photon excited lanthanide luminescence in solution, whereas
      dipicolinic acid and carbostyril-124 do not give rise to any detectable two
      photon excited lanthanide luminescence using modest excitation powers (<20 mW
      focused at the sample) in the 700-1000 nm range.

PMID- 15986062
TI  - Intramolecular charge transfer processes in donor-acceptor substituted
      vinyltetrahydropyrenes.
AB  - Two novel donor-acceptor-substituted vinyltetrahydropyrene derivatives, 2-N,N
      dimethylamino-7-(1-carbethoxyvinyl)-4,5,9,10-tetrahydropyrene, , and 2-N,N
      dimethylamino-7-(1,1-dicyanovinyl)-4,5,9,10-tetrahydropyrene, , were synthesized
      and their photophysical properties investigated in solvents of different
      polarities. Our studies revealed the existence of intramolecular charge transfer
      excited states in these molecules. For both compounds the fluorescence maxima
      exhibited solvent polarity-dependent red shifts. These were quantitatively
      analysed by the Lippert-Mataga and Liptay equations to obtain the excited state
      dipole moments. Our results indicated that in the case of , emission takes place
      from a planar (1)CT state in all non-protic solvents. In the case of , the nature
      of the excited state depends on the solvent. A fast relaxation to a triplet state
      is proposed in cyclohexane. The emitting state in medium polar solvents is a
      planar (1)CT state. In highly polar solvents a twisted (1)CT state is invoked to
      explain the low fluorescence quantum yield. For both compounds CT nature of the
      emitting states were further confirmed by studies in acidic medium. The ground
      and excited state pK(a) values for and were determined using absorption and
      emission spectral changes observed in the presence of protic acids.

PMID- 15986063
TI  - Competitive radiative and reactive relaxation channels in the excited state decay
      of some thio-analogues of EE-distyrylbenzene.
AB  - The photophysical and photochemical properties of some thio-analogues of
      symmetrically substituted EE-1,4-distyrylbenzene (linear conjugation) and EE-1,3
      distyrylbenzene (crossed conjugation), where thiophene rings replace the side
      benzene rings or the central benzene ring, have been investigated. The kinetic
      competition between the radiative and reactive relaxation channels of the lowest
      excited singlet state has been compared with that found for the corresponding
      hydrocarbons. The photobehaviour markedly depends on the type of conjugation and
      on the position (2' or 3') of the ethenic bridge with respect to the sulfur atom.
      The main effect of the heteroatom is an increase in the photoisomerization yield
      due to a decrease of the torsional barrier in S(1) and to an increase in the S(1)
      -> T(1) intersystem crossing, which opens the way to isomerization in the triplet
      manifold. Conformational equilibria, due to restricted rotation around the quasi
      single bonds with the ethenic carbons, have also been investigated by selective
      photoexcitation for the compounds with side 3'-thienyl groups.

PMID- 15986064
TI  - Asthma severity and genetics in Taiwan.
AB  - The prevalence of childhood asthma in Taiwan has increased dramatically during
      the last 2 to 3 decades. In Taipei city, the prevalence of asthma in
      schoolchildren has increased from 1.3% in 1974 to 19.0% in 2003. Genetic mapping
      and candidate gene analyses have revealed suggestive evidence for linkage of
      asthma to a number of different chromosomal regions and for association with
      several candidate genes. Over 70 variants in candidate genes have been reported
      to be associated with these phenotypes. The main regions these variants have been
      found are on chromosomes 2q, 5q, 6p, 11q, 12q, 16q and 17q. Five potential asthma
      susceptibility genes or complexes have been identified using a positional
      approach. These are A desintegrin and metalloproteinase 33 (ADAM33), dipeptidyl
      peptidase 10 (DPP10), plant homeodomain zinc finger protein 11 (PHF11) and SET
      domain, bifurcated 2, G-protein related receptor for asthma (GPRA) and serine
      protease inhibitor Kazal type 5 (SPINK5). It is also evident that environmental
      factors will influence the expression of genes and the ultimate clinical
      phenotype of asthma and atopy. Evidence for a genetic contribution to risk for
      fatal or near-fatal asthma in Caucasians and Taiwanese has been suggested. We
      have revealed that the regulation upon activation, normal T cell expressed and
      secreted (RANTES)-28C/G polymorphism exacerbates asthma severity and represents a
      genetic risk factor for life-threatening asthma attacks in Chinese children.
      Moreover, in the Chinese children the frequency of the chemoattractant receptor
      homologous molecule expressed on T helper 2 cells (CRTH2) 1651G allele in near
      fatal asthmatics was significantly higher than in mild-to-moderate asthmatics and
      normal controls. The CRTH2 1651G allele of single nucleotide polymorphism
      re545659 was also associated with a higher degree of bronchial
      hyperresponsiveness.

PMID- 15986065
TI  - Reactive nitrogen intermediate production and tolerance variability in different
      mouse strains after in vivo treatment with lipopolysaccharide from Salmonella
      abortus equi.
AB  - Lipopolysaccharide (LPS) stimulation in animal models generates a large number of
      immune factors including cytokines and mediators. It also acts as a potent
      inducer of macrophage reactive oxygen intermediates and reactive nitrogen
      intermediates (RNI). RNI as stable metabolites of nitric oxide (NO) are produced
      by cells stimulated with LPS and cytokines. In this study, LPS from Salmonella
      abortus equi was investigated as an inducer of RNI in untreated controls and test
      groups of white Naval Medical Research Institute (NMRI) mice. Animals were
      humanely killed at 30, 60, 120 and 180 min after LPS injection, and plasma RNI
      was measured by Griess microassay. In a further experiment, host tolerance
      against bacterial LPS was evaluated by sequential intravenous injection of LPS
      concentrations of 4, 1 and 0.5 mg/kg at 24 h intervals in NMRI and with the same
      schedule but via subcutaneous injection in Balb/c mice. Statistical analysis of
      RNI values using analysis of variance test indicated that in vivo LPS stimulation
      induced high levels of NO in murine hosts (p<0.001). Comparison of RNI levels at
      different times after administration revealed the largest amount of RNI at 180
      min after inoculation. Analysis of the time course until maximum RNI induction
      indicated that NMRI mice had the longest delay, suggesting a difference in
      tolerance of NMRI and Balb/c mice to LPS stimulation dependent on LPS
      concentration, dose, and route of inoculation.

PMID- 15986066
TI  - Humoral and cellular immune response after measles vaccination in Taiwan.
AB  - Measles immunoglobulin G (IgG) seroepidemiologic studies have been widely used to
      monitor the effectiveness of measles immunization programs in Taiwan. However,
      studies about cellular immunity against the measles virus have been lacking. This
      study surveyed cellular immunity after measles, mumps and rubella combined
      vaccine (MMR) immunization in Taiwan. Seventy six people between 1 and 80 years
      of age were enrolled. All patients lived in northern Taiwan, and none of them had
      immunodeficient disease. Every enrolled patient donated a tube of heparinized
      blood between January 2004 and June 2004 for cross-sectional studies of IgG
      seroepidemiologic and MMR-specific lymphoproliferative response. The results
      showed that the current 3-dose (measles x 1 + MMR x 2) measles immunization
      program induced slightly higher IgG seroprevalence (100% vs 85%, p=0.244) and a
      higher frequency of significant (stimulation indices > or = 3) MMR-specific
      lymphoproliferative response (50% vs 15%, p=0.044) than a 2-dose (measles x 1 +
      MMR x 1) immunization program, although there was no difference in IgG titers and
      stimulation indices. Furthermore, the population aged older than 36 years (pre
      immunization era) had higher IgG titers and seroprevalence, and similar MMR
      specific lymphoproliferative responses to that of the population aged younger
      than 36 years (post-immunization era). In summary, with the limited data, the
      current 3-dose (measles x 1 + MMR x 2) measles immunization policy probably more
      effectively induces humoral and cellular immunity than the 2-dose (measles x 1 +
      MMR x 1) policy. Measles IgG seroprevalence in populations of different age
      groups exceeds nearly 90%. Measles has been eliminated temporarily in Taiwan. For
      a better understanding of the durability of vaccine-induced immunity and in order
      to establish the most appropriate immunization schedule, long-term and large
      scale prospective studies of measles-specific seroepidemiology and cellular
      immunity will be needed.

PMID- 15986067
TI  - A seroepidemiologic study of Helicobacter pylori and hepatitis A virus infection
      in primary school students in Taipei.
AB  - Helicobacter pylori and hepatitis A virus (HAV) share a common fecal-oral
      transmission route. The aim of this study was to investigate the prevalence of
      and risk factors for H. pylori and HAV infection in primary school students in
      Taiwan. We studied 289 Grade 1 to 6 students from a single primary school in
      Taipei County in 2003. The students volunteered for blood tests for H. pylori
      immunoglobulin G (IgG) antibody and anti-hepatitis A antibody after consent from
      their parents. Questionnaires were administered to the parents to investigate
      possible risk factors. The seroprevalence rates of H. pylori IgG antibody and
      anti-hepatitis A antibody were 21.5% (62/289) and 1.4% (4/289), respectively. No
      statistically significant relationship was found between seropositivity for H.
      pylori and for HAV. If parents had knowledge of H. pylori and HAV, their children
      were significantly more likely to be seronegative for H. pylori (p=0.020, odds
      ratio [OR] 2.1, 95% confidence interval [CI] 1.2-3.7) and HAV (p=0.012, OR 11.2,
      95% CI 1.5-83.4). Students whose family members had no history of HAV infection
      were significantly less likely to be seropositive for HAV (p=0.001, OR 0.04, 95%
      CI 0.004-0.5). No other factors were found to be significantly associated with
      seropositivity, including blood type; age; gender; family members' history of H.
      pylori infection; travel to China; parents' educational level; sources of water
      supply; family members' use of tobacco, alcohol, or betel nut; family members'
      history of peptic ulcer or gastritis; and students' history of recurrent
      abdominal pain. Lack of public health knowledge appears to be related to
      seroprevalence of H. pylori in primary school students. The low seroprevalence of
      anti-HAV antibodies demonstrates the lack of protection against this infection in
      school-age children in Taiwan and suggests that universal administration of HAV
      vaccine would be wise.

PMID- 15986068
TI  - Clinical management and outcome of childhood lung abscess: a 16-year experience.
AB  - In order to evaluate the clinical manifestations, management and outcome of
      childhood lung abscess, a retrospective chart review of 27 pediatric patients
      with International Classification of Diseases, Ninth Revision-Clinical
      Modification (ICD-9 CM) code of 503.1 (lung abscess) from August 1987 to August
      2003 was conducted. Among the 27 patients (14 males and 13 females), 30% (8/27)
      were primary lung abscess and 70% (19/27) had underlying chronic diseases
      (secondary lung abscess). The predisposing factors of the primary group (n = 8)
      included 6 cases of respiratory tract infection, 1 with choking during swimming,
      and 1 with laceration wound. The underlying diseases in the secondary group (n =
      19) included 10 cases of hematologic disorder (52%), 3 of congenital heart
      disease, 2 of central nervous system anomalies, and 1 each of hyperimmunoglobulin
      E syndrome, chronic lung disease, liver cirrhosis with fistula formation, and
      Swyer-James syndrome. Eleven patients (41%) underwent diagnostic tapping,
      including echo-guided aspiration (10 cases) and computed tomography-guided
      percutaneous needle aspiration (1 case). Positive yield rate from aspiration of
      lung abscess was 63.6% (7/11). Surgical intervention was performed in 8 (42%) of
      the secondary group and in 1 patient from the primary group. The pathogens were
      identified in 11 patients (41%): 5 with oral flora, 2 with Staphylococcus aureus
      plus other pathogens, 1 with S. aureus alone, 1 with Pseudomonas aeruginosa plus
      Proteus mirabilis, 1 with P. aeruginosa alone, and 1 with Aspergillus. The
      average duration of parenteral antibiotic use was 40 days. Five cases (18.5%)
      died due to poor control of the underlying diseases, and 4 of the patients (15%)
      had sequelae (2 with bronchiectasis and 2 with lung fibrosis). Seventy percent of
      lung abscess occurred in children with underlying medical conditions. Early
      percutaneous aspiration has an important role in identification of pathogens.
      Oral anaerobes and S. aureus are the core pathogens in primary lung abscess and
      gram-negative pathogens should also be considered in secondary lung abscess.

PMID- 15986069
TI  - Comparison of the characteristics of culture-negative versus culture-positive
      septic arthritis in children.
AB  - Septic arthritis in children can be difficult to diagnose and may be associated
      with severe morbidity. A majority of apparent septic arthritis cases may have
      negative culture, thereby creating a dilemma regarding treatment. The medical
      charts of 209 children with the diagnosis of septic arthritis were
      retrospectively reviewed to evaluate the differences between culture-negative (n
      = 64) and culture-positive (n = 145) cases. Demographic data, clinical
      manifestations, treatment, and outcome were analyzed. Laboratory data recorded
      included white blood cell count, erythrocyte sedimentation rate, C-reactive
      protein, imaging studies, and culture results. Patients with culture-negative
      arthritis had a significantly lower incidence of fever (56.3% vs 70.3%, p=0.047),
      local pain or tenderness (42.2% vs 69.7%, p=0.0001), changes in the overlying
      skin (45.3% vs 62.1%, p=0.024), motion limitation (25.0% vs 42.8%, p=0.014), and
      osteomyelitis (25.0% vs 40.7%, p=0.029). Culture-negative patients had a longer
      duration of symptoms or signs before diagnosis (10.1 +/- 8.9 days vs 6.5 +/- 5.7
      days, p=0.046) and a shorter antimicrobial course (24.5 +/- 5.1 days vs 35.7 +/-
      8.1 days, p=0.001). Children with culture-negative septic arthritis had a lower
      prevalence of residual joint dysfunction at 6 months after treatment (3.1% vs
      11.7%, p=0.046). In conclusion, children with culture-negative septic arthritis
      have milder clinical manifestations, earlier response to treatment, and a better
      outcome than those with culture-positive disease.

PMID- 15986070
TI  - Alcaligenes xylosoxidans bacteremia: clinical features and microbiological
      characteristics of isolates.
AB  - Bacteremia caused by Alcaligenes xylosoxidans is rare. Between 1999 and 2002, 12
      cases of bacteremia caused by A. xylosoxidans were diagnosed at a tertiary
      referral center in central Taiwan. The clinical features of these patients and
      the antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE)
      pattern of their blood isolates were studied. All infections were acquired
      nosocomially. All of the adult patients had underlying diseases, and 10 (83%) had
      undergone an invasive procedure. The clinical syndrome included primary
      bacteremia in 7 patients (58%), and catheter-associated bacteremia, surgical
      wound infection, pneumonia, urinary tract infection, and empyema in 1 each.
      Polymicrobial bacteremia was found in 1 patient. The case-fatality rate was 17%
      (2/12). All isolates were susceptible to piperacillin and ceftazidime and
      resistant to aminoglycoside, ciprofloxacin and cefepime. Susceptibility to
      imipenem (67%), ampicillin-sulbactam (75%) and trimethoprim-sulfamethoxazole
      (92%) was variable. Genetic fingerprints obtained by PFGE showed identical
      pattern in the isolates from 2 neonates, indicating the epidemiologic relatedness
      of these infections. We conclude that A. xylosoxidans isolates are multi
      resistant and A. xylosoxidans bacteremia should be considered as a possible
      etiology of infection after invasive procedures in patients with underlying
      diseases. Strict infection control is needed to prevent this infection.

PMID- 15986071
TI  - Epidemiologic analysis and antifungal susceptibility of Candida blood isolates in
      southern Taiwan.
AB  - Candidemia is a clinically important disease which has increased in incidence
      worldwide in recent decades. In order to identify the risk factors for mortality
      in candidemic patients and to elucidate the role of antifungal susceptibility
      testing, a retrospective cohort study was performed of 56 episodes of candidemia
      in 1998 at a medical center in southern Taiwan. The minimal inhibitory
      concentration (MIC) of these isolates was determined by E-test. Malignancy and
      alimentary diseases (42.9%) were the most common underlying conditions of these
      patients. There was no difference of Candida spp. distribution among patients
      treated in medical or surgical departments, except that all 5 isolates of C.
      intermedia were found in patients treated in medical departments (p=0.02) and 50%
      of candidemic infants had C. parapsilosis isolates (p=0.046). Among all Candida
      isolates, 3 (5.4%) were fluconazole non-susceptible. C. tropicalis had a
      significantly higher rate of amphotericin B resistance than the other species
      (p=0.007). Thirty four patients died and 70.6% of these deaths were attributable
      to candidemia. Thrombocytopenia, septic shock at the date of candidemia onset, C
      reactive protein > 100 mg/L, blood urea nitrogen > 20 mg/dL, length of stay < 60
      days, and Acute Physiology and Chronic Health Evaluation II score > or = 10
      points were significantly associated with the death attributable to candidemia.
      Thrombocytopenia was the only independent predictor for mortality in the
      multivariate analysis. When the breakpoint of fluconazole was set at 2 microg/mL,
      as opposed to 8 microg/mL as in the National Committee for Clinical Laboratory
      Standards (NCCLS) criteria, the clinical outcome of death was significantly
      correlated to the MICs of the blood isolates. The correlation between MIC of
      fluconazole determined by E-test data, which is more easily obtainable than with
      NCCLS methods, and outcome requires larger scale investigation.

PMID- 15986072
TI  - Impact of the 1997 revised Centers for Disease Control criteria on case rates of
      legionellosis in Taiwan: review of 38 cases at a teaching hospital, 1998-2002.
AB  - In 1997, the United States Centers for Disease Control and Prevention (CDC)
      published revised case definitions for legionellosis which eliminated the
      previously used category of "probable case" based on a single indirect
      fluorescence antibody (IFA) titer. This study evaluated the influence of revision
      on the case rates of legionellosis in Taiwan. From 1988 to 2002, 4615 patients
      with pneumonia were tested for legionellosis in our hospital. The testing methods
      included IFA assay for serum specimens and direct fluorescence antibody (DFA)
      assay for sputum specimens. Using the revised criteria, Legionnaires' disease
      (LD) was diagnosed by DFA in 27 cases and by IFA in 11 cases. The most common
      underlying conditions were cigarette smoking (44.7%), chronic obstructive
      pulmonary disease (28.9%) and corticosteroid use (26.3%). The clinical features
      were nonspecific, including fever (73.7%), dyspnea (63.2%), cough (63.2%) and
      leukocytosis (63.2%). The overall mortality rate was 18.4%, and the directly LD
      attributable mortality rate was 10.5%. Nasogastric tube insertion, endotracheal
      intubation, congestive heart failure before the onset of LD, inappropriate
      antimicrobial therapy, respiratory failure and absence of fever during the LD
      course were significantly associated with LD-attributable mortality. Older age
      (>70 years) was not associated with higher mortality (p=0.053). Using the revised
      diagnostic criteria in our series, the positive rate of case identification by
      IFA was 0.26%, while use of the previous case definitions resulted in a positive
      rate of 7.6% (including probable and definitive cases). Recognition that the
      original CDC criteria of IFA titer >1:256 or elevation of IFA titer <4-fold in
      paired sera could not adequately define an LD etiology has led to a dramatic
      lowering of case rates among studies after the criteria revision in Taiwan and
      elsewhere. Assays that are faster, more sensitive and less technician dependent
      are needed to diagnosis this disease.

PMID- 15986073
TI  - Thymoma and hypogammaglobulinemia (Good's syndrome): a case report.
AB  - Good's syndrome is extremely rare and refers to an acquired B and T cell
      immunodeficiency in thymoma patients. We report a 51-year-old female thymoma
      patient who presented with recurrent herpes zoster, pneumonia, diarrhea and
      opportunistic infections. She was found to have acquired hypogammaglobulinemia
      with absent B cells. Despite repeat intravenous immunoglobulin replacement and
      antibiotic therapy, she died of bacterial pneumonia-induced acute respiratory
      distress syndrome. Clinicians should look for evidence of immunologic dysfunction
      in thymoma patients presenting with recurrent infections.

PMID- 15986074
TI  - Hanta hemorrhagic fever with renal syndrome: a case report and review.
AB  - Hantavirus infection is seldom reported in Taiwan. The spectrum of clinical
      severity ranges from mild to severe and may cover Hantavirus pulmonary syndrome
      and hemorrhagic fever with renal syndrome (HFRS). We report a case of HFRS in a
      24-year-old soldier presenting with fever, chills, abdominal pain and generalized
      myalgia. His clinical course progressed through febrile, hypotensive, oliguria
      and polyuria phases. Hantavirus infection was proven by serology at the second
      hospital week. The patient was successfully treated with supportive management.
      Clinicians should be alert to the possibility of HFRS when examining patients
      with symptoms of fever, renal function impairment, hemorrhagic tendency and with
      rural exposure in Taiwan.

PMID- 15986075
TI  - An unusual case of ulcerative colitis with concurrent extraintestinal
      manifestations of primary sclerosing cholangitis, thromboembolism, hemolytic
      anemia, and hemochromatosis.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of intestines
      associated with a large number of extraintestinal manifestations (EIMs) which
      significantly contribute to its morbidity and mortality. A 32-year-old man
      presented with ulcerative colitis (UC) accompanied by the unusual coexisting
      clinical manifestations of primary sclerosing cholangitis, thromboembolism, and
      hemolytic anemia during the disease course. The incidental finding of
      hemochromatosis of the liver was attributed to chronic hemolysis. The full-blown
      EIMs and systemic complications in this patient did not appear to be attributable
      to drug treatment and/or infection but might have been related to both the
      underlying immune-mediated mechanism and the lack of early and adequate treatment
      for UC and its associated complications. This case emphasizes the need for early
      and aggressive treatment of IBD accompanied by EIMs to avoid morbidity and
      mortality.

PMID- 15986076
TI  - Mycophenolate mofetil: a dermatologic perspective.
AB  - Introduced in the 1970s as a treatment for psoriasis, mycophenolic acid has since
      been reformulated as mycophenolate mofetil (MMF). With an improved side-effect
      profile and enhanced bioavailability, MMF is a promising drug for immune-mediated
      skin disease. Currently approved for the prevention of organ rejection, its list
      of "off-label" dermatologic indications continues to grow. As a noncompetitive
      inhibitor of inosine monophosphate dehydrogenase (IMPDH), MMF inhibits de novo
      purine synthesis. Its relative lack of hepatonephrotoxicity and seemingly low
      risk of carcinogenicity offer important therapeutic advantages. While case
      reports and case series dominate the dermatologic literature, preliminary results
      are sufficiently promising to warrant larger, randomized clinical trials with
      this emerging therapy.

PMID- 15986077
TI  - Twelve technical strategies to the perfect surgical scar.

PMID- 15986078
TI  - Imiquimod 5% cream for the treatment of actinic keratoses.
AB  - Actinic keratoses (AKs) are premalignant inflammatory skin lesions with the
      potential to transform into squamous cell carcinoma (SCC). There are several
      treatment options available for patients presenting with multiple AKs. Imiquimod
      is believed to stimulate and enhance host immune responses locally against skin
      tumors and viral infections. Five clinical studies to date have demonstrated its
      safety and efficacy in the treatment of actinic keratoses. Long-term follow-up
      studies examining recurrence rates are limited.

PMID- 15986079
TI  - The surgical correction of protuberant ears.
AB  - While prominent ears are considered a sign of good fortune in the Far East,
      Western society looks upon prominent ears in a far less positive manner. Children
      with prominent ears are often the subjects of verbal and at times physical abuse
      by their peers, resulting in adverse psychological effects. Advances in otoplasty
      have made it possible not only to pin back the ears, but also to reshape them,
      reduce their size, or make them more symmetrical. For a dermatologic surgeon, an
      otoplasty may be an unfamiliar surgical procedure, however, the surgery itself
      does not significantly differ from ear wedges or cartilage removal procedures for
      skin cancer, procedures with which the dermatologic surgeon is quite familiar.

PMID- 15986080
TI  - Pimecrolimus and tacrolimus: the US FDA public health advisory.

PMID- 15986081
TI  - Surgical techniques for scar revision.
AB  - Patients frequently seek cosmetic improvement for existing scars. While no scar
      can be completely erased, dermatologic surgeons can employ a variety of
      approaches to achieve more esthetically pleasing scars. Classification of a scar
      abnormality guides the choice of treatment technique. Lasers and injectables are
      useful tools; however, for certain scar abnormalities, scalpel-based surgery
      remains the mainstay. This review focuses on common incisional surgical methods
      for scar revision.

PMID- 15986082
TI  - Moisturizers: what they are and a practical approach to product selection.
AB  - Moisturizers are widely used products that are important in many dermatologic and
      cosmetic skin therapies. They contain varying combinations of emollients,
      occlusives, and humectants to achieve their beneficial effects, and there is an
      overwhelming number of formulations available. To develop a rational approach for
      prescribing moisturizers, commercially available products can be categorized on
      the basis of application site.

PMID- 15986083
TI  - Poly-L-lactic acid as a facial filler.
AB  - Poly-L-lactic acid is a filler recently approved by the US FDA for the correction
      of facial lipoatrophy in patients infected with the human immunodeficiency virus
      (HIV). Currently, poly-L-lactic acid, sold under the brand name Sculptratrade
      mark (Dermik), is the only product approved by the FDA specifically for this
      indication. The market for poly-L-lactic acid will likely be larger than the HIV
      infected population, as physicians use poly-L-lactic acid off-label to correct
      lipoatrophy associated with the normal aging process in non-HIV-infected
      patients. The benefits of poly-L-lactic acid are limited by the fact that
      multiple treatments are necessary to achieve the desired correction; its results
      are temporary and its cost is high.

PMID- 15986084
TI  - Histamine, histamine receptors (H1 and H2), and histidine decarboxylase
      expression by chondrocytes of osteoarthritic cartilage: an immunohistochemical
      study.
AB  - Degeneration and loss of articular cartilage are the characteristic features of
      osteoarthritis (OA), with the appearance of fibrillations, cell clusters, matrix
      depletion, and changes in matrix composition all apparent. Histamine has a
      recognised role in allergic and inflammatory reactions, and is reported to affect
      several aspects of chondrocyte behaviour. The immunohistochemical (IHC) studies
      reported here have demonstrated histamine (H), both H1 and H2 receptors, and the
      histamine-producing enzyme histidine decarboxylase (HDC) in a variable proportion
      of human articular chondrocytes in OA cartilage specimens. Such observations were
      especially evident within the degenerative, superficial zone, and more so in late
      stage disease. By contrast, "normal" age-matched cartilage specimens showed
      relatively little immunopositive staining for histamine and HDC. These findings
      strongly suggest that histamine and H-receptor expression by HAC in OA cartilage
      is potentially an important contributor to the atypical, aberrant phenotype of OA
      chondrocytes.

PMID- 15986085
TI  - Rapidly-progressive glomerulonephritis in a patient with Behcet's disease:
      successful treatment with intravenous cyclophosphamide.
AB  - We report a case of rapidly-progressive glomerulonephritis complicating Behcet's
      disease (BD). A 44-year-old male has suffered from recurrent oral ulcers and
      retinal vasculitis developed 2 years ago. He complained of abdominal pain and
      papulopustular skin lesions. Multiple ulcers were seen on the colon on
      colonoscopy. Routine renal work-up revealed heavy proteinuria and hematuria.
      Renal biopsy demonstrated crescentic glomerulonephritis. Most symptoms improved
      after steroid therapy, except for urinary abnormalities. At this point,
      intravenous monthly cyclophosphamide pulse therapy was undergone. After the sixth
      pulse therapy, proteinuria and hematuria were dramatically improved and renal
      function was well preserved.

PMID- 15986086
TI  - The effect of pulsed electromagnetic fields in the treatment of cervical
      osteoarthritis: a randomized, double-blind, sham-controlled trial.
AB  - The purpose of this study was to evaluate the effect of electromagnetic field
      therapy (PEMF) on pain, range of motion (ROM) and functional status in patients
      with cervical osteoarthritis (COA). Thirty-four patients with COA were included
      in a randomized, double-blind study. PEMF was administrated to the whole body
      using a mat 1.8 x 0.6 m in size. During the treatment, the patients lay on the
      mat for 30 min per session, twice a day for 3 weeks. Pain levels in the PEMF
      group decreased significantly after therapy (p<0.001), but no change was observed
      in the placebo group. The active ROM, paravertebral muscle spasm and neck pain
      and disability scale (NPDS) scores improved significantly after PEMF therapy
      (p<0.001) but no change was observed in the sham group. The results of this study
      are promising, in that PEMF treatment may offer a potential therapeutic adjunct
      to current COA therapies in the future.

PMID- 15986088
TI  - Radiotherapy in the management of Klippel-Trenaunay-Weber syndrome: report of two
      cases.
AB  - Klippel-Trenaunay-Weber syndrome (KTWS) is characterized by combined vascular
      malformations of capillary, venous, and lymphatic types usually observed during
      infancy or childhood. In this report, we describe two KTWS patients treated with
      radiotherapy after long-term conservative treatment or multiple surgical
      interventions. The first patient, a 15-year-old female, presented with vascular
      masses located on the right upper extremity. She was treated conservatively for
      14 years, and amputation was offered at the age of 14 due to cardiac failure. A
      course of radiotherapy to a total dose of 40 Gy with conventional daily
      fractionation was administered as an alternative to the mutilating surgery, and
      prominent improvement both subjectively and objectively was detected 1 year after
      radiotherapy. The second patient, a 40-year-old male, suffered from huge vascular
      masses of both the trunk and lower extremities. Despite multiple surgical
      interventions and conservative treatment, disease progressed and neurological
      symptoms occurred due to compression of vertebral structures. He was administered
      a course of 30 Gy radiotherapy with 1.5 Gy daily fractions to the lower thoracic
      region and whole abdominal cavity. Six months after radiotherapy, subjective
      relief described by the patient but without any objective response was detected.
      Though considered as a benign disease, KTWS can cause life-threatening
      complications. The response of one of our patients is a hopeful finding for
      considering radiotherapy as an alternative treatment modality for these patients.

PMID- 15986087
TI  - Soluble HLA: patterns of expression in normal subjects, autoimmune diseases, and
      transplant recipients.

PMID- 15986089
TI  - Is endovascular therapy the preferred treatment for all visceral artery
      aneurysms?
AB  - Endovascular intervention can provide an alternative method of treatment for
      visceral artery aneurysms. We conducted a retrospective review of all patients
      with visceral artery aneurysms at a single university medical center from 1990 to
      2003, focusing on the outcome of endovascular therapy. Sixty-five patients with
      visceral artery aneurysms were identified: 39 splenic (SAA), 13 renal, seven
      celiac, three superior mesenteric (SMA), and three hepatic. Eleven patients
      (16.9%) had symptoms attributable to their aneurysms, which included a total of
      four ruptures (6.2%): three splenic and one hepatic. Management consisted of 18
      (27.7%) endovascular interventions, nine (13.9%) open surgical repairs, and 38
      (58.5%) observations. Mean aneurysm diameter for patients treated expectantly was
      significantly less than for those who underwent intervention (p = 0.001).
      Endovascular interventions included 15 (83.3%) embolizations (11 SAA, three
      renal, one hepatic) and three (16.7%) stent grafts (two SMA, one renal). The
      initial technical success rate of the endovascular procedures was 94.4% (17/18).
      However, there were four patients (22.2%) with major endovascular procedure
      related complications: one late recurrence requiring open surgical repair, two
      large symptomatic splenic infarcts, and one episode of severe pancreatitis. These
      four patients had distal splenic artery aneurysms at or adjacent to the splenic
      hilum. There were no endovascular procedure-related deaths. Reasons for
      performing open surgical repair included three SAA ruptures diagnosed at
      laparotomy and complex anatomy not amenable to endovascular intervention (six
      patients). One surgical patient had a postoperative small bowel obstruction
      treated nonoperatively; and there was one perioperative death in a patient
      operated on emergently for rupture. Endovascular management of visceral artery
      aneurysms is a reasonable alternative to open surgical repair in carefully
      selected patients. Individual anatomic considerations play an important role in
      determining the best treatment strategy if intervention is warranted. However,
      four of 11 (36.4%) patients with distal splenic artery aneurysms treated with
      endovascular embolization developed major complications. Based on our experience,
      traditional surgical treatment of SAA with repair or ligation and concomitant
      splenectomy when necessary may be preferred in these cases.

PMID- 15986090
TI  - Protein/protein interactions (PDZ) in proximal tubules.

PMID- 15986091
TI  - Involvement of aquaporin-5 water channel in osmoregulation in parotid secretory
      granules.
AB  - Aquaporins (AQPs) are a family of channel proteins that allow water or very small
      solutes to pass, functioning in tissues where the rapid and regulated transport
      of fluid is necessary, such as the kidney, lung, and salivary glands. Aquaporin-5
      (AQP5) has been demonstrated to localize on the luminal surface of the acinar
      cells of the salivary glands. In this paper, we investigated the expression and
      function of AQP5 in the secretory granules of the rat parotid gland. AQP5 was
      detected in the secretory granule membranes by immunoblot analysis. The
      immunoelectron microscopy experiments confirmed that AQP5 was to be found in the
      secretory granule membrane. Anti-AQP5 antibody evoked lysis of the secretory
      granules but anti-aquaporin-1 antibody did not and AQP1 was not detected in the
      secretory granule membranes by immunoblot analysis. When chloride ions were
      removed from the solution prepared for suspending secretory granules, the granule
      lysis induced by anti-AQP5 antibody was inhibited. Furthermore, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, an anion channel blocker, blocked
      the anti-AQP5 antibody-induced secretory granule lysis. These results suggest
      that AQP5 is, expressed in the parotid gland secretory granule membrane and is
      involved in osmoregulation in the secretory granules.

PMID- 15986092
TI  - Partitioning of tetrachlorophenol into lipid bilayers and sarcoplasmic reticulum:
      effect of length of acyl chains, carbonyl group of lipids and biomembrane
      structure.
AB  - We report results of a partitioning study of 2,3,4,6-tetrachlorophenol (TeCP). In
      the study we explored (1) the effect of the length of acyl chains of lipids
      (C16:1 - C24:1) and alkanes (C6-C16), (2) the role of the carbonyl group of
      lipids, and (3) the effect of molecular structure of the sarcoplasmic reticulum
      membrane on TeCP partitioning. Mole fraction partition coefficients have been
      measured using equilibrium dialysis for un-ionized (HA), and ionized (A) species,
      Kp(x) (HA), Kp(x) (A). Their values are concentration-dependent. Partition
      coefficients were analyzed in terms of a model that accounts for saturation of
      membrane associated with the finite area of partition site, and electrostatic
      interactions of (A-) species with charged membrane. Limiting values of partition
      coefficients, corresponding to infinite dilution of solute, Kp(x0) (HA), Kp(x0)
      (A) were obtained. Kp(x0) (HA) and Kp(x0) (A ) measure the strength of solute
      membrane interactions. Studies were done with single-layered vesicles of lipids
      with variable chain length: 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine
      (C16:1), 1,2-dioleoyl-sn-glycero-3-phosphocholine (C18:1), 1,2-dierucoyl-sn
      glycero-3-phosphocholine (C22:1), and 1 ,2-dinervonoyl-sn-glycero-3
      phosphocholine (C24:1), and egg-PC. Kp(x0) for transfer of TeCP from water into
      lipid membranes was found to be independent of the length of acyl chains, whereas
      Kp(x0) for transfer from water into alkanes increased with the length of alkane.
      The effect of the carbonyl CO group of lipids on partitioning was measured using
      1,2-di-o-octadecenyl-sn-glycero-3-phosphocholine (CO absent) and 1,2-dioleoyl-sn
      glycero-3-phosphocholine (CO present) liposomes. Carbonyl groups, known to change
      dipolar potential, had no effect on partitioning. Partition coefficients of un
      ionized and ionized forms of TeCP were invariant to the presence of proteins and
      other membrane components of sarcoplasmic reticulum (SR) membrane.

PMID- 15986093
TI  - Functional interaction between CFTR and Cx45 gap junction channels expressed in
      oocytes.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride (Cl(
      )) channel known to influence the function of other channels, including connexin
      channels. To further study potential functional interactions between CFTR and gap
      junction channels, we have co-expressed CFTR and connexin45 (Cx45) in Xenopus
      oocytes and monitored junctional conductance and voltage sensitivity by dual
      voltage clamp electrophysiology. In single oocytes expressing CFTR, an increase
      in cAMP caused by forskolin application induced a Cl(-) current and increased
      membrane conductance; application of diphenylamine carboxylic acid (CFTR blocker)
      readily blocked the Cl(-) current. With co-expression of CFTR and Cx45,
      application of forskolin to paired oocytes induced a typical outward current and
      increased junctional conductance (G(j)). In addition, the presence of CFTR
      reduced the transjunctional voltage sensitivity of Cx45 channels without
      affecting the kinetics of junctional current inactivation. The drop in voltage
      sensitivity was further enhanced by forskolin application. The data indicate that
      CFTR influences cell-to-cell coupling mediated by Cx45 channels.

PMID- 15986094
TI  - Normal CFTR Activity and Reversed Skin Potentials in Pseudohypoaldosteronism.
AB  - Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) Cl(-) channel
      function is required for activating amiloride-sensitive epithelial Na(+) channels
      (ENaC) in salt-absorbing human sweat duct. It is unclear whether ENaC channel
      function is also required for CFTR activation. The dysfunctional ENaC mutations
      in type-1 pseudohypoaldosteronism (PHA-1) provided a good opportunity to study
      this phenomenon of ion channel interaction between CFTR and ENaC. The PHA-1 ducts
      completely lacked spontaneous ENaC conductance (gENaC). In contrast, the normal
      ducts showed large spontaneous gENaC (46 +/- 10 ms, mean +/- SE: ). After
      permeabilization of the basolateral membrane with alpha-toxin, cAMP + ATP
      activation of CFTR Cl(-) conductance (gCFTR) or alkalinization of cytosolic pH
      (6.8 to 8.5) stimulated gENaC of normal but not PHA-1 ducts. In contrast, both
      spontaneous gCFTR in intact ducts and (cAMP + ATP)-activated gCFTR of
      permeabilized ducts appeared to be similar in normal and PHA-1 subjects. Lack of
      gENaC completely blocked salt absorption and caused dramatic reversal of skin
      potentials associated with pilocarpine-induced sweat secretion from significantly
      negative in normal subjects (-13 +/- 7.0 mV) to significantly positive (+22 +/-
      11.0 mV) in PHA-1 patients. We conclude that virtual lack of ENaC in PHA-1 ducts
      had little effect on CFTR activity and that the positive skin potentials could
      potentially serve as a diagnostic tool to identify type-1
      pseudohypoaldosteronism.

PMID- 15986096
TI  - Shape transformations of protein-like copolymer globules.
AB  - Shapes of globules formed by amphiphilic multi-block-copolymers in a selective
      solvent are considered theoretically. We focus on copolymers consisting mostly of
      insoluble H-units forming large core surrounded by a shell of soluble P-blocks.
      It is shown that the globule becomes non-spherical when the effective shell
      tension is low enough. The resultant shape depends on the shell bending energy:
      it is prolate if this energy is larger than the elastic energy of the core, and
      oblate in the opposite case. The central result is the prediction of the
      formation of a surface pattern of fingers accompanying or even preempting the
      shape transition mentioned above. We elucidate and discuss the following finger
      morphologies: 1) nearly spherical knob; 2) a necklace of spherical beads
      extending away from the surface; 3) mostly cylindrical fingers; 4) large thorn
      like fingers. The first 3 morphologies develop at equilibrium as the shell area
      increases (or, equivalently, the shell tension decreases). Considering the
      relevant kinetical aspects we show that formation of fingers is a nucleation and
      growth process, and that the energy of their equilibrium nucleation is likely to
      be high. Therefore, the finger formation may be delayed, and may actually occur
      in the regime where the plain spherical surface is metastable. It is the last
      morphology (thorn-like fingers) that characterizes the metastable regimes when
      the finger formation is controlled by a high activation energy. The universal
      features of the above predictions inviting experimental tests are discussed.

PMID- 15986097
TI  - Stationary cell size distributions and mean protein chain length distributions of
      Archaea, Bacteria and Eukaryotes described with an increment model in terms of
      irreversible thermodynamics.
AB  - In terms of an increment model irreversible thermodynamics allows to formulate
      general relations of stationary cell size distributions observed in growing
      colonies. The treatment is based on the following key postulates: i) The growth
      dynamics covers a broad spectrum of fast and slow processes. ii) Slow processes
      are considered to install structural patterns that operate in short periods as
      temporary stationary states of reference in the sense of irreversible
      thermodynamics. iii) Distortion during growth is balanced out via the many fast
      processes until an optimized stationary state is achieved. The relation deduced
      identifies the numerous different stationary patterns as equivalents, predicting
      that they should fall on one master curve. Stationary cell size distributions of
      different cell types, like Hyperphilic archaea, E. coli (Prokaryotes) and S.
      cerevisiae (Eukaryotes), altogether taken from the literature, are in fact
      consistently described. As demanded by the model they agree together with the
      same master curve. Considering the "protein factories" as subsystems of cells the
      mean protein chain length distributions deduced from completely sequenced genomes
      should be optimized. In fact, the mean course can be described with analogous
      relations as used above. Moreover, the master curve fits well to the patterns of
      different species of Archaea, Bacteria and Eukaryotes. General consequences are
      discussed.

PMID- 15986098
TI  - Urethral prolapse after durasphere injection.
AB  - Urethral prolapse is an uncommon condition among adult patients. We report a case
      of adult female patient with urethral prolapse after Durasphere injection. The
      patient was successfully treated with excision of the prolapsed urethra and
      Durasphere mass, and fibrin glue injection to support the remaining part of
      urethra.

PMID- 15986099
TI  - Large thigh abscess after placement of synthetic transobturator sling.
AB  - PURPOSE: To report a unique complication associated with transobturator slings.
      MATERIALS AND METHODS: The evaluation and treatment of a unique infectious
      complication of transobturator slings is reviewed. RESULTS: A large thigh abscess
      associated with a transobturator sling was diagnosed and treated. CONCLUSION: New
      techniques of sling placement may be associated with unique infectious
      complications. Slings passing through the obturator foramen and thigh can lead to
      a significant abscess within the adductor muscles of the thigh.

PMID- 15986100
TI  - Prevalence of symptomatic pelvic organ prolapse in a Swedish population.
AB  - Our aim was to estimate the prevalence of symptomatic pelvic organ prolapse (POP)
      in a Swedish urban female population. The cross-sectional study design included
      8,000 randomly selected female residents in Stockholm, 30-79-year old. A postal
      questionnaire enquired about symptomatic POP, using a validated set of five
      questions, and about urinary incontinence and demographic data. Of 5,489 women
      providing adequate information, 454 (8.3%, 95% confidence interval 7.3-9.1%) were
      classified as having symptomatic POP. The prevalence rose with increasing age but
      leveled off after age 60. In a logistic regression model that disentangled the
      independent effects, parity emerged as a considerably stronger risk factor than
      age. There was a ten-fold gradient in prevalence odds of POP with parity, the
      steepest slope (four-fold) being between nulliparous and primiparous women. The
      prevalence of frequent stress urinary incontinence was 8.9% and that of frequent
      urge incontinence 5.9%. Out of the 454 women with prolapse, 37.4% had either or
      both types of incontinence.

PMID- 15986102
TI  - Multiple primary cancers of separate organ sites: implications for research and
      cancer control (Australia).
AB  - OBJECTIVE: To identify cancers which occur as second primaries following the
      diagnosis of cancers of other sites, as a basis for formulating causal hypotheses
      and planning medical surveillance. METHODS: Analyses of fifteen common cancer
      sites were undertaken to examine the occurrence of multiple primaries. These
      cancers were notified to the South Australian Cancer Registry during 1977-2001.
      Historic cohort models were used where standardised incidence ratios (95
      confidence limits) were calculated to indicate the risk of second primary
      cancers. RESULTS: New associations detected included an increased risk of cancers
      of the bladder, colon, rectum, kidney and melanomas following a diagnosis of
      prostate cancer and an increased risk of leukaemia following both lung and rectal
      cancer. Many previously identified combinations of multiple primaries were
      confirmed. CONCLUSIONS: From the wide range of associations identified, some such
      as leukaemias occurring as second primaries after the diagnosis of ovarian
      cancers and lymphomas may be a treatment effect. The diagnosis of multiple
      primary cancers in the same month (e.g. bladder-prostate cancers and ovarian
      uterine cancers) may reflect patterns of medical testing and the long preclinical
      phases of some cancers.

PMID- 15986101
TI  - Effect of osteoporosis treatments on risk of non-vertebral fractures: review and
      meta-analysis of intention-to-treat studies.
AB  - Most osteoporosis treatments have proven efficacy in reducing the risk of
      vertebral fractures, whereas evidence is less straightforward for prevention of
      non-vertebral fractures. Conclusions as to the efficacy of a treatment should be
      based primarily on analyses of the intention to treat (ITT) population rather
      than on exploratory subgroup analyses; however, non-vertebral anti-fracture
      efficacy has been largely derived by post-hoc subgroup analyses. This review and
      meta-analysis was performed to assess non-vertebral anti-fracture efficacy of
      several osteoporosis therapies, including a more stringent assessment of the ITT
      populations. Data on non-vertebral anti-fracture efficacy, a defined endpoint of
      the ITT analyses and confirmed by radiographs, were obtained from randomized,
      placebo-controlled, phase III clinical trials of at least 3-year duration. Meta
      analyses were performed for the two bisphosphonates, alendronate and risedronate.
      Relative risks (RR), 95% confidence intervals (CI) and statistical significance
      for active treatment compared with placebo were calculated. Eleven clinical
      trials met the criteria for review, three of which showed statistically
      significant ( P < or =0.05) non-vertebral anti-fracture efficacy in the ITT
      population: two trials with risedronate and one trial with strontium. A meta
      analysis showed significant reductions in the relative risk of non-vertebral
      fracture for both alendronate (RR=0.86; 95% CI: 0.76-0.97, P =0.012) and
      risedronate (RR=0.81; 95% CI: 0.71-0.92, P =0.001). Risedronate and strontium
      ranelate were the only treatments to show non-vertebral anti-fracture efficacy in
      this robust assessment of anti-fracture efficacy of osteoporosis therapy using
      ITT populations in trials of 3 years or more in duration. Risedronate was the
      only agent shown to demonstrate efficacy in more than one trial. Meta-analysis
      showed that both alendronate and risedronate provide non-vertebral anti-fracture
      efficacy.

PMID- 15986103
TI  - Hormone replacement therapy is not associated with an increased risk of leukemia
      (United States).
AB  - OBJECTIVE: Recent studies have reported an increased risk of certain cancers
      associated with hormone replacement therapy (HRT), possibly due to stimulation of
      estrogen receptors. Since estrogen receptors are expressed on certain
      hematopoietic cells, it is possible that HRT use may also increase the risk of
      leukemia. METHODS: A cohort of 37,172 post-menopausal Iowa women ages 55-69 years
      with no history of prior cancer was linked annually to the population-based state
      cancer registry through 2001. In addition to other self-reported cancer risk
      factors, participants were asked about current and former use of HRT in 1986 and
      on four subsequent follow-up questionnaires. A total of 201 cases of leukemia
      were identified over 16 years of follow-up including 74 acute myeloid leukemias
      (AMLs) and 87 chronic lymphocytic leukemias (CLLs). RESULTS: Compared to never
      users of HRT at study baseline, current [multivariate relative risk (RR), 1.09;
      95% confidence interval (CI) 0.70-1.71)] and former users (RR=0.82, 95% CI=0.59
      1.15) were at no increased risk of developing leukemia. For AML, current users
      also had no increased risk (RR=0.83, 95% CI=0.37-1.84) and there was a suggestion
      that former users had a slightly decreased risk (RR=0.66, 95% CI=0.37-1.17). For
      CLL, all RRs were around unity. CONCLUSION: We conclude that HRT is unlikely to
      be an appreciable risk factor for leukemia.

PMID- 15986104
TI  - Lifestyle factors and the risk of adult leukemia in Canada.
AB  - OBJECTIVES: To evaluate the impact of active smoking, obesity, and dietary
      intakes on the risk of adult leukemia. METHODS: We analysed data obtained from a
      population-based case-control study conducted in eight Canadian provinces. Risk
      estimates were generated by applying multivariate logistic regression methods to
      1068 incident histologically confirmed leukemia cases and 5039 controls aged 20
      74. RESULTS: We found a statistically significant increased risk for acute
      myeloid leukemia (AML) associated with active smoking, with a clear dose-response
      relationship and an adjusted odds ratio (OR) of 1.5 (95% confidence interval
      [CI]=1.1-2.0) for heavy smokers reporting more than 20 pack-years of cigarette
      smoking. We also observed positive associations with the highest body mass index
      (BMI) for AML, chronic myeloid leukemia, and chronic lymphoid leukemia with a
      significant dose-response relationship. No association with leukemia was observed
      for the intake of fruits and vegetables, and the effect of active smoking on
      adult leukemia risk was not modified by fruits and/or vegetables consumption or
      obesity. However, the positive risk for AML associated with active smoking
      disappeared among subjects with high BMI (> or =30 kg/m2). CONCLUSIONS: Our study
      contributes to the accumulating evidence linking AML and active smoking, and
      provides some evidence that obesity increases the risk of most of the adult
      leukemia subtypes.

PMID- 15986105
TI  - Social inequalities and cancer mortality in France, 1975-1990.
AB  - OBJECTIVE: to investigate social inequalities in cancer mortality from 1975
      through 1990 among men and women in France. METHODS: A sample, that included
      census data for approximately 1% of the French population, has been followed for
      mortality from 1975 to 1990. Causes of death were obtained through a record
      linkage with the French national cause-of-death file. The analysis was restricted
      to those aged 35:59 in 1975 and included 61,876 men and 65,291 women.
      Occupational class, coded according to the social class scheme of Erikson,
      Goldthorpe and Portecarero in 7 categories, and educational level (in 4
      categories) in 1975 have been studied. The analysis has been conducted for 15
      cancer sites among men and 13 among women. Analysis used a Cox proportional
      hazards model. RESULTS: For educational level, inequalities among men were more
      pronounced for cancers of the pharynx Relative Risk (RR) lowest versus highest
      educational level=9.2, 95% Confidence Interval (CI) 2.9-29.1, larynx (RR=6.2,
      CI=3.0:12.6), oral cavity (RR=2.7, CI=1.3-5.3), lung (RR=3.5, CI=2.5-4.8),
      esophagus (RR=3.1, CI=1.9-5.2), stomach (RR=2.5, CI=1.2-5.3) and rectum (RR=3.4,
      CI=1.2-9.6). No association between educational level and cancer mortality was
      observed for cancers of either the colon or lymphatic and hematopoietic tissue.
      Social inequalities were less pronounced among women but nevertheless observed
      for cancer of the uterus (RR=1.9, CI=1.0-3.6), stomach (RR=4.1, CI=1.0-17.1) and
      lung (RR=1.6, CI=0.7-3.7). No associations were found for mortality from breast
      or ovarian cancers. Results were similar when socioeconomic status was measured
      by occupational class. CONCLUSION: The analysis showed substantial inequalities
      in cancer mortality in France, with large differences according to cancer site.

PMID- 15986106
TI  - Occupational class, occupational mobility and cancer incidence among middle-aged
      men and women: a prospective study of the French GAZEL cohort*.
AB  - OBJECTIVE: To examine the association between occupational class, occupational
      mobility and cancer incidence in the 1990s. METHODS: Prospective study of 14,853
      men and 5493 women employed by a large French company. Incident cases (any
      cancer, smoking and alcohol-related, breast) were ascertained through a validated
      company-based cancer registry (1990-2002). Hazard ratios (HRs) by occupational
      class and by career-long occupational mobility were calculated adjusting for age,
      marital status, tobacco and alcohol consumption, weight, diet, asbestos exposure,
      family history of cancer, and reproductive history. RESULTS: 359 male cancers
      (107 smoking and alcohol-related) and 208 female cases (120 breast cancers) were
      observed. Male clerks and manual workers were at high risk, particularly of
      smoking and alcohol-related cancers (compared to managers, age-adjusted HRs: 2.95
      95% CI 1.37-6.38 and 2.18 95% CI 1.15-4.11). Adjusting for specific health
      behaviors and other cancer risk factors reduced this gradient (fully-adjusted HRs
      respectively 1.95 95% CI 0.89-4.27 and 1.54 95% CI 0.80-2.97). The risk was also
      associated with occupational mobility. We found no association between women's
      occupational class and cancer. CONCLUSION: The incidence of smoking and alcohol
      related cancers among French men shows a strong socioeconomic gradient. Policies
      addressing these social disparities are needed.

PMID- 15986107
TI  - Adipose levels of dioxins and risk of breast cancer.
AB  - OBJECTIVE: Our objective was to evaluate the breast cancer risk associated with
      body burden levels of polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs). METHODS: We conducted a hospital-based
      case-control study among 79 women diagnosed with invasive breast cancer and 52
      controls diagnosed with benign breast conditions. We collected breast adipose
      tissue and analyzed it for all 17 2,3,7,8-substitituted PCDD/PCDFs. We used
      unconditional logistic regression to calculate age- and race-adjusted exposure
      specific odds ratios (ORs) and 95% confidence intervals (CI) for each individual
      PCDD/PCDF congener as well as for the summary measures (I-TEQ, Adj-TEQ). RESULTS:
      Dioxin levels were consistent with reports from other small, contemporary studies
      of body burdens in the U.S. None of the odds ratios for any of the congeners or
      summary measures differed significantly from one. Especially for the PCDF
      congeners, point estimates tended to be below one. One notable exception was
      octachlorodibenzo-p-dioxin (OCDD), for which the odds ratio for the second and
      third tertiles appeared modestly elevated (OR = 1.22, 95% CI: 0.47:3.16 and OR =
      1.62, 95% CI: 0.64:4.12, respectively), though the test for trend was not
      significant (p = 0.36). CONCLUSION: Breast cancer risk was not associated with
      adipose levels of PCDD/PCDFs. More study is suggested among women of color who
      may have higher body burden levels of these compounds.

PMID- 15986108
TI  - Previous oral contraceptive use and breast cancer risk according to hormone
      replacement therapy use among postmenopausal women.
AB  - OBJECTIVE: To assess postmenopausal breast cancer risk in relation to particular
      patterns of oral contraceptive (OC) use according to hormone replacement therapy
      (HRT) exposure. METHODS: Time-dependent Cox regression models were used to
      analyse information on postmenopausal women from a large-scale French cohort.
      Among a total of 68,670 women born between 1925 and 1950, 1405 primary invasive
      postmenopausal breast cancer cases were identified from 1992 to 2000. RESULTS: A
      non-significant decrease in risk of around 10% was associated with ever OC use as
      compared to never OC use in postmenopausal women. No significant interaction was
      found between OC and HRT use on postmenopausal breast cancer risk. Breast cancer
      risk decreased significantly with increasing time since first OC use (test for
      trend: p=0.01); this was consistent after adjustment for duration of use or for
      time since last use. CONCLUSION: No increase in breast cancer risk was associated
      with previous OC exposure among postmenopausal women, probably because the
      induction window had closed. Some women may develop breast cancer soon after
      exposure to OCs, leading to a deficit of cases of older women. Further
      investigation is therefore required to identify young women at high risk.

PMID- 15986109
TI  - Life After Cancer Epidemiology (LACE) Study: a cohort of early stage breast
      cancer survivors (United States).
AB  - The Life After Cancer Epidemiology (LACE) Study, a cohort of 2321 early stage
      breast cancer survivors, was established in 2000 to examine how modifiable
      behavioral risk factors affect quality of life and long-term survival. Women were
      recruited primarily from the Kaiser Permanente Northern California Cancer
      Registry (KPNCAL) and the Utah cancer registry (UCR), United States. Baseline
      data were collected, on average, at two years post-diagnosis through self
      administered questionnaires that included information on demographics, medical
      history, anthropometry, diet, supplements, physical activity and quality of life.
      The purpose of this paper is to describe the creation and baseline
      characteristics of the cohort. Forty-six percent of women to whom questionnaires
      were mailed agreed to participate. The cohort which is 80% white, was diagnosed
      predominantly with Stage I and II breast cancer (93%), and will have been
      followed for 5.6 years post-diagnosis, on average, by the end of 2004. Women
      reported slightly over four daily servings of fruit and vegetables, well below
      the suggested 5-A-Day national guidelines. Compared to women free of cancer,
      physical activity patterns were similar, while weight gain, especially in younger
      women, was higher than is typical. These data suggest that in the early years
      post-diagnosis, breast cancer survivors exhibit similar patterns to the general
      population in many health behaviors.

PMID- 15986110
TI  - A case for informed consent? Indoor UV tanning facility operator's provision of
      health risks information (United States).
AB  - OBJECTIVE: Indoor UV tanning is associated with skin cancer. This study describes
      consumer health risks information provided by indoor UV tanning facility
      operators in four states (Colorado, Illinois, Texas, and Wisconsin) with varying
      operator training, regulations, enforcement and penalties. METHODS: Using a cross
      sectional survey study design, 100 randomly selected licensed indoor UV tanning
      facilities from each state were surveyed anonymously by telephone. Facility
      operators were questioned regarding the provision of information on potential
      adverse effects of indoor UV exposure. RESULTS: Of 628 licensed indoor UV tanning
      facilities contacted, 400 facilities were surveyed. Most (87%) advised patrons of
      the potential risk of sunburn from indoor tanning. Less than half of facility
      operators in Colorado, Texas and Wisconsin informed patrons about the risk of
      skin cancer (42, 43 and 48%, respectively) compared with 81% of Illinois
      operators. Likewise, more operators in Illinois reported the risk of premature
      aging (79%) compared with other states (41% Colorado, 43% Texas and 51%
      Wisconsin). CONCLUSIONS: Tanning facility operators frequently misinformed
      patrons of indoor UV exposure risks. The provision of informed consent by indoor
      tanning facility operators needs improved adaptation by the tanning industry as a
      standard for customer service.

PMID- 15986112
TI  - Secular trends in the incidence, mortality, and survival rate of gastric cancer
      in a general Japanese population: the Hisayama study.
AB  - To examine secular trends in the incidence and mortality of gastric cancer in a
      Japanese community, Hisayama, we established three study-cohorts of Hisayama
      residents aged > or =40 years in 1961 (1637 subjects), 1974 (2054), and 1988
      (2602). Each cohort was followed up for ten years. The age-standardized mortality
      from gastric cancer significantly decreased from 2.4 per 1000 person-years in the
      first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2,
      respectively, for women (p < 0.01 for trend in both sexes). The five-year
      survival rate after gastric cancer significantly improved from the first (32.6%)
      to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05),
      respectively, for women. The age-standardized incidence of cancer in men was not
      different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the
      second, and 4.9 in the third cohort), while it decreased significantly in women
      (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our
      findings suggest that in a Japanese population, the mortality from gastric cancer
      declined during the past 40 years, due mainly to the improvement of survival in
      both sexes and a decrease in the incidence for women.

PMID- 15986111
TI  - C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in
      healthy women within the European Prospective Investigation into Cancer and
      Nutrition (EPIC).
AB  - OBJECTIVES: The risk of some cancers is positively associated with body weight,
      which may influence circulating levels of sex-steroid hormones, insulin and IGF
      I. Interrelationships between these hormones and the associations with adiposity
      were evaluated in healthy women participating in the European Prospective
      Investigation into Cancer and Nutrition (EPIC). METHODS: A cross-sectional
      analysis was performed on anthropometric and hormonal data from 743 pre- and 1217
      postmenopausal women. Body mass index (BMI) and waist circumference were used as
      indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth
      Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding
      globulin (SHBG) were measured by immunoassays; free sex steroid concentrations
      were calculated. RESULTS: BMI and waist circumference were positively correlated
      with estrogens in postmenopausal women and with C-peptide, free testosterone and
      inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated
      with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I
      was positively associated with postmenopausal estrogens and androgen
      concentrations in all women. CONCLUSIONS: Sex-steroid concentrations appear to be
      regulated along several axes. Adiposity correlated directly with estrogens in
      postmenopausal women and with insulin, resulting in lower SHBG and increased
      levels of free sex steroids. Independent of adiposity and insulin, IGF-I was
      associated with decreased SHBG levels, and increased concentrations of androgens
      and postmenopausal estrogens.

PMID- 15986113
TI  - Risk of non-small cell lung cancer and the cytochrome P4501A1 Ile462Val
      polymorphism.
AB  - OBJECTIVE: The Ile462Val substitution in the cytochrome P450 1A1 gene (CYP1A1)
      results in increased enzymatic activity. Preliminary data suggesting a link
      between this polymorphism and lung cancer risk in Caucasians are inconsistent,
      reflecting small sample sizes and the relatively low frequency of the variant.
      METHODS: The data set consisted of 1050 primary non-small cell lung cancer cases
      and 581 controls, a large homogenous population designed specifically to address
      previous inconsistencies. Patients were genotyped using a PCR-RFLP technique.
      RESULTS: Carriers of the valine allele, CYP1A1*2C, (Ile/Val or Val/Val genotypes)
      were significantly over-represented in non-small cell lung cancer compared to
      controls (OR=1.9; 95% CI=1.2-2.9; p=0.005) when adjusted for confounders,
      particularly in women (OR=4.6; 95% CI=1.7-12.4; p=0.003). The valine variant was
      statistically significantly over-represented in cases of lung cancer younger than
      the median age (64 years) (OR=2.5; 95% CI=1.3-4.8; p=0.005) and cases with less
      than the median cumulative tobacco-smoke exposure (46 pack-years) (OR=2.4; 95%
      CI=1.3-4.7; p=0.007). CONCLUSIONS: These new data establish an association
      between the CYP1A1 Ile462Val polymorphism and the risk of developing non-small
      cell lung cancer, especially among women.

PMID- 15986114
TI  - Pediatric brain tumors in non-Hispanics, Hispanics, African Americans and Asians:
      differences in survival after diagnosis.
AB  - BACKGROUND: Racial differences in survival for children with brain tumors have
      not been well studied, particularly in Hispanics and Asians. The objective of
      this study was to assess racial differences in survival of children with brain
      tumors, focusing on Hispanics, African Americans and Asians compared to Non
      Hispanics. METHODS: Subjects identified through the SEER Program were 2799
      children, < or =19 years old at diagnosis, newly diagnosed between 1973 and 1996
      with primary, malignant brain tumors. Chi-square tests were used to evaluate
      prognostic variables by race. Kaplan-Meier models and Cox proportional hazards
      models were used to assess racial differences in overall survival and in survival
      by histological type of tumor. RESULTS: The distribution histological type of
      tumor varied significantly by race. Overall survival was similar for Hispanics,
      African Americans, Asians compared to Non-Hispanics, although trends of increased
      risk of death for the minority groups were noted when stratifying by histological
      type of tumor. CONCLUSIONS: Racial differences in survival could exist by
      histological type of tumor, but further work is necessary for a more complete
      understanding of these differences.

PMID- 15986115
TI  - Cancer of the gastrointestinal tract and exposure to asbestos in drinking water
      among lighthouse keepers (Norway).
AB  - OBJECTIVE: Previous studies of predominantly ecological design have indicated a
      possible elevation of gastrointestinal cancer risk in population groups exposed
      to drinking water contaminated with asbestos from natural sources or asbestos
      cement containing water pipes. In the present study the possible effect of
      ingested asbestos fibers on gastrointestinal cancer risk was investigated in an
      occupational group where a proportion of the employees was exposed to asbestos in
      their drinking water. METHOD: A cohort of 726 lighthouse keepers first employed
      between 1917 and 1967 were followed up for cancer incidence from 1960 to 2002.
      The standardized incidence ratio (SIR) was calculated as the number of new cancer
      cases divided by the expected number based on five-year age and sex specific
      incidence rates in the general rural population of Norway. A 95% confidence
      interval (CI) was calculated for all SIR values assuming a Poisson distribution
      of the cancer cases. RESULTS: Risk of stomach cancer was elevated in the whole
      cohort (SIR: 1.6, CI: 1.0-2.3), in the subgroup with definite asbestos exposure
      (SIR: 2.5, CI: 0.9-5.5), and when the group was followed for 20 years and more
      after first possible exposure (SIR: 1.7, CI: 1.1-2.7). Less consistent results
      were found for colon cancer; SIR was 1.5 (CI: 0.9-2.2) overall, 0.8 (CI: 0.1-2.9)
      among the exposed, and 1.6 (CI: 1.0-2.5) twenty years and more after first
      possible exposure. CONCLUSION: The results support the hypothesis of an
      association between ingested asbestos and gastrointestinal cancer risk in general
      and stomach cancer risk specifically.

PMID- 15986116
TI  - Risk of non-Hodgkin lymphoma associated with occupational exposure to solvents,
      metals, organic dusts and PCBs (Australia).
AB  - OBJECTIVE: Several studies have suggested that there is an occupational component
      to the causation of non-Hodgkin lymphoma (NHL). We aimed to use accurate means to
      assess occupational exposures to solvents, metals, organic dusts and
      polychlorinated biphenyls (PCBs) in a case-control study. METHODS: Cases were
      incident NHLs during 2000 and 2001 in two regions of Australia. Controls were
      randomly selected from the electoral roll and frequency matched to cases by age,
      sex and region. A detailed occupational history was taken from each subject. For
      jobs with likely exposure to the chemicals of interest, additional questions were
      asked by telephone interview using modified job specific modules. An expert
      allocated exposures using the information in the job histories and the
      interviews. Odds ratios were calculated for each exposure adjusting for age, sex,
      region and ethnic origin. RESULTS: 694 cases and 694 controls (70 and 45
      respectively of those potentially eligible) participated. The risk of NHL was
      increased by about 30 for exposure to any solvent with a dose response
      relationship, subgroup analysis showed the finding was restricted to solvents
      other than benzene. Exposure to wood dust also increased the risk of NHL
      slightly. Exposures to other organic dusts, metals, and PCBs were not strongly
      related to NHL. CONCLUSIONS: The risk of NHL appears to be increased by exposure
      to solvents other than benzene and possibly to wood dust.

PMID- 15986117
TI  - Antioxidants and basal cell carcinoma of the skin: a nested case-control study.
AB  - OBJECTIVE: To investigate the relationship between basal cell carcinoma (BCC) and
      antioxidant nutrients, specifically carotenoids, vitamin E and selenium. METHODS:
      The Nambour Skin Cancer Study is an ongoing, community-based study of randomly
      selected adult residents of a township in sub-tropical Queensland, Australia.
      Using a nested case-control design, incident cases of BCC (n=90) were compared
      with age and sex matched controls (n=90). Dietary exposure was measured using
      food frequency questionnaire estimates of intake as well as serum biomarkers.
      Other determinants of skin cancer including sun exposure were also considered.
      Dietary intakes were adjusted for energy intake, and serum carotenoids and
      vitamin E were adjusted for serum cholesterol. Odds ratios were calculated across
      quartiles of dietary intake and serum biomarkers and linear trends were assessed
      using logistic regression, adjusting for age, sex and supplement use. RESULTS AND
      CONCLUSIONS: In this prospective study no significant associations were found
      between BCC and carotenoids, vitamin E or selenium, as measured by serum
      biomarkers or dietary intake, although there was a suggestion of a positive
      association with lutein intake.

PMID- 15986118
TI  - Racial and ethnic disparities in breast cancer rates by age: NAACCR Breast Cancer
      Project.
AB  - OBJECTIVE: To examine age-specific rates of breast cancer incidence among racial
      and ethnic groups in the United States. METHODS: Subjects were 363,801 women
      diagnosed with invasive breast cancer diagnosed during 1994--1998 and reported in
      the North American Association of Central Cancer Registries (NAACCR) data set.
      Variables analyzed included race, ethnicity, 5-year age group (from 10 years
      through 85+years), and stage at time of diagnosis (localized, regional, distant).
      Incidence rates per 100,000 women were calculated for each 5--year age group and
      stratified by stage. Rate ratios and 95% confidence intervals were calculated by
      comparing each racial group with whites and Hispanics with non-Hispanics.
      RESULTS: Black women experience significantly higher breast cancer incidence up
      to the age of 40 years and significantly lower incidence after age 50 compared
      with white women of the same ages. This is called the 'crossover' effect. This
      shifting burden of higher incidence occurs at ages 35--39 for localized stage and
      at ages 55--59 for regional stage. For distant stage, black women of all ages
      experience higher incidence compared with white women. Similar crossover effects
      do not exist for American Indian (AI) or Asian/Pacific Islander (API) women
      compared with white women. Both AI and API women have significantly lower
      incidence of breast cancer compared with white women, and Hispanic women have
      significantly lower incidence compared with non-Hispanic women. CONCLUSIONS: This
      study highlights racial and ethnic differences in breast cancer incidence rates
      among US women. The crossover effect between black and white women, particularly
      the lower incidence of localized stage disease diagnosed in older black women, is
      a significant phenomenon that may be associated with screening practices, and has
      implications for public health planning and cancer control initiatives to reduce
      racial/ethnic disparities.

PMID- 15986119
TI  - An ecological study of the association of environmental chemicals on breast
      cancer incidence in Texas.
AB  - PURPOSE: To investigate the role of environment in breast cancer development, we
      conducted an ecological study to examine the association of releases for selected
      industrial chemicals with breast cancer incidence in Texas. METHODS: During 1995-
      2000, 54,487 invasive breast cancer cases were reported in Texas. We identified
      12 toxicants released into the environment by industry that: (1) were positively
      associated with breast cancer in epidemiological studies, (2) were Environmental
      Protection Agency (EPA) Toxics Release Inventory (TRI) chemicals designated as
      carcinogens or had estrogenic effects associated with breast cancer risk, and (3)
      had releases consistently reported to EPA TRI for multiple Texas counties during
      1988--2000. We performed univariate, and multivariate analyses adjusted for race
      and ethnicity to examine the association of releases for these toxicants during
      1988--2000 with the average annual age-adjusted breast cancer rate at the county
      level. RESULTS: Univariate analysis indicated that formaldehyde, methylene
      chloride, styrene, tetrachloroethylene, trichloroethylene, chromium, cobalt,
      copper, and nickel were positively associated with the breast cancer rate.
      Multivariate analyses indicated that styrene was positively associated with the
      breast cancer rate in women and men (beta=0.219, p=.004), women (beta=0.191,
      p=0.002), and women >or= 50 years old (beta=0.187, p=0.002). CONCLUSION: Styrene
      was the most important environmental toxicant positively associated with invasive
      breast cancer incidence in Texas, likely involving women and men of all ages.
      Styrene may be an important breast carcinogen due to its widespread use for food
      storage and preparation, and its release from building materials, tobacco smoke,
      and industry.

PMID- 15986120
TI  - The importance of temporal effects in evaluating the prognostic impact of joint
      ERPR expression in premenopausal women with node-positive breast cancer.
AB  - Although there is abundant information about the independent effects of estrogen
      receptor (ER) and progesterone receptor (PR) on outcomes of breast cancer,
      comparatively little is known about the impact of joint (ER+PR+, ER+PR-, ER-PR+
      and ER-PR-) ERPR expression. The purpose of this study was to evaluate the
      prognostic relevance of joint ERPR expression to progression free survival (PFS).
      Data from 710 patients with a median follow-up of 119 months has been analyzed
      retrospectively. Our results indicate that the effect of the ER+PR+ phenotype on
      PFS was significantly time-dependent (p<0.0001); favorable in the first 3 years
      of follow-up (HR=0.67, p=0.0175) compared to ER-PR- phenotype, but unfavorable
      during the later follow-up period (HR=2.89, p=0.0006). Similar patterns were also
      observed for ER+PR- and ER-PR+ phenotypes, but the effect did not reach
      statistical significance. In the tree-based analysis, we found that, among
      patients with more than 4 positive nodes and age greater than 40, those with ER
      PR+ tumors had the worst PFS ( p=0.025), and among patients with 1--3 positive
      nodes and stage of T1 and T2, those with ER+PR- had the worst outcome ( p=0.006).
      Our results demonstrate that failure to recognize the time-varying effect of the
      steroid hormonal receptors can obscure their role in the prognosis of breast
      cancer. We also provide more evidence to support the concept that ER-PR+ is a
      real group representing a distinct clinical entity.

PMID- 15986121
TI  - Transcription factor decoy against promoter C of estrogen receptor alpha gene
      induces a functional ER alpha protein in breast cancer cells.
AB  - This study addresses the hypothesis that transfection of oligonucleotide
      mimicking a negative regulatory sequence of promoter C of estrogen receptor alpha
      (ER alpha) gene is sufficient for its re-expression in ER-negative human cancer
      cell lines. Even if the negative transcription regulator subtracted by the
      transcription factor decoy is not yet been identified, we demonstrated that after
      this decoy treatment, the cells produced a functional ER alpha protein able to
      respond to 17-beta-estradiol and to transactivate a transfected estrogen response
      element (ERE)-regulated reporter gene. The effects of reactivated ER alpha
      protein and its estrogen dependence on endogenous target gene expression level,
      such as ER beta, have been also assessed. The proliferation of the cells
      transfected with low levels of decoy was significantly increased by estrogen and
      not by tamoxifen, suggesting that the levels of reactivated ER alpha in these
      decoy conditions confers a certain hormone sensitivity. On the contrary, high
      level expression of ER alpha obtained at high doses of transfected decoy molecule
      produced a progressive decrease of cell proliferation. Since ER alpha is
      important in the transcription of different genes and its loss is involved in
      several pathological processes including neoplastic and chronic diseases, our
      findings may be of relevance for a possible new therapeutical approach of such
      diseases.

PMID- 15986122
TI  - Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer.
AB  - Binding of IGF-1 to the type I IGF receptor starts a signalling cascade that
      plays an important role in regulating cell proliferation, differentiation and
      apoptosis. The interaction between the IGF-1 and its receptor is mainly regulated
      by a binding protein, IGFBP 3. We studied a CA repeat polymorphism 969 bp
      upstream of the transcription start site in the IGF-1 gene and an A-202 C
      polymorphism in the IGFBP 3 gene and tested their association with breast cancer
      risk using four case-control series with a total of 787 cases and 900 controls.
      We did not find any association between the breast cancer risk and the IGF-1
      repeat length (19 versus non-19) or the IGFBP 3 A-202 C polymorphism in the
      postmenopausal breast cancer series or in women diagnosed for breast cancer under
      the age of 50. In the familial breast cancer series we observed a non
      significantly increased odds-ratio (OR) in homozygotes for the non-19 alleles of
      the IGF-1 gene (OR 1.51, 95% CI 0.96-2.39, p=0.07). Similarly, in the familial
      breast cancer series we detected an increased frequency of the IGFBP 3 -202 C
      allele carriers (OR 1.50, 95% CI 1.05--2.14, p=0.03). The association was
      stronger in individuals homozygous for these alleles (OR 3.76, 95% CI 1.44-v
      9.81, p=0.006). Thus, the polymorphisms in the IGF-1 and IGFBP 3 genes associated
      with an increased risk of breast cancer in familial cases carrying the variant
      alleles.

PMID- 15986123
TI  - GREB 1 is a critical regulator of hormone dependent breast cancer growth.
AB  - BACKGROUND: Estrogen plays a central role in breast cancer pathogenesis and many
      potent risk factors for the development of the disease can be explained in terms
      of increased lifetime exposure to estrogen. Although estrogen regulated genes
      have been identified, those critically involved in growth regulation remain
      elusive.METHODS. To identify candidate genes involved in estrogen stimulated
      breast cancer growth, DNA microarray based gene expression profiles were
      generated from three estrogen receptor alpha (ER alpha) positive breast cancer
      cell lines grown under multiple stimulatory and inhibitory conditions. RESULTS:
      Only three genes were significantly induced by 17beta-estradiol (E2) relative to
      control in all three cell lines: GREB 1, stromal cell-derived factor 1 (SDF-1)
      and trefoil factor 1 (pS2). Quantitative real-time PCR assays confirmed that in
      all three cell lines, GREB 1 was induced by E2, but not by the antiestrogens
      tamoxifen (TAM) or ICI 182,780. GREB 1 expression level was strongly correlated
      with ER alpha positivity in 39 breast cancer cell lines of known ER alpha
      expression status. GREB 1 induction by E2 was rapid (7.3 fold by 2 h for MCF-7)
      and mirrored the fraction of cells entering S-phase when released from an
      estrogen deprivation induced cell arrest. Suppression of GREB 1 using siRNA
      blocked estrogen induced growth in MCF-7 cells and caused a paradoxical E2
      induced growth inhibition. CONCLUSION: These data suggest that GREB 1 is
      critically involved in the estrogen induced growth of breast cancer cells and has
      the potential of being a clinical marker for response to endocrine therapy as
      well as a potential therapeutic target.

PMID- 15986124
TI  - Patterns of toxicity in older patients with breast cancer receiving adjuvant
      chemotherapy.
AB  - OBJECTIVE: To retrospectively determine the relationship of age to toxicity from
      adjuvant chemotherapy for breast cancer. DESIGN AND METHODS: We identified 1,405
      consecutive patients age 65 or older with primary invasive breast cancer who were
      seen at Memorial Sloan-Kettering Cancer Center from January 1998 to December
      2000. Patients selected from this cohort for analysis were aged 65 or older at
      diagnosis; received their follow-up care at Memorial Sloan-Kettering Cancer
      Center; had stage I, II, or III breast cancer; and received adjuvant chemotherapy
      consisting of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil), an
      anthracycline-based regimen (AC [doxorubicin and cyclophosphamide], or AC-T [AC
      and paclitaxel or docetaxel]). Exclusion criteria included prior chemotherapy or
      previous breast cancer. RESULTS: One hundred thirty-two patients were included in
      this study, with a mean age of 70 (range 65--79). Comorbidity measured by the
      Charlson comorbidity index was low: score 0 (83%), 1 (12%), 2 (5%); with stages:
      I(18%), IIA (41%), IIB (27%), IIIA (8%), IIIB (6%), T1Nx (1%). Patients receiving
      an anthracycline-based regimen were more likely to experience grade 3 or 4
      toxicity (p=0. 01), require hospitalization (p<0.001), and/or develop febrile
      neutropenia (p<0.001). Treatment delays due to myelosuppression occurred more
      frequently in patients receiving CMF (p<0.001). The type of chemotherapy regimen
      (anthracycline compared to CMF) was a better predictor for toxicity than
      increased age or comorbidity score. CONCLUSIONS: In this cohort of older patients
      with breast cancer, the risk for toxicity from adjuvant chemotherapy depended
      more on the type of regimen (anthracycline vs. CMF) than the patient's
      chronological age.

PMID- 15986125
TI  - Cosmetic outcome of breast conserving therapy after sentinel node biopsy versus
      axillary lymph node dissection.
AB  - INTRODUCTION: Next to locoregional control, good cosmetic outcome is one of the
      main goals of breast conserving treatment (BCT) for breast cancer surgery.
      Factors affecting cosmetic outcome are well known. The sentinel node (SN)
      procedure avoids lymphedema in the breast, which might influence cosmetic
      outcome. The aim of this study was to evaluate the cosmetic outcome of BCT after
      the SN procedure compared to that after axillary lymph node dissection (ALND).
      METHODS: The subjects were 20 patients who underwent ALND and 20 patients who
      underwent the SN procedure. After a minimum follow-up period of 43 months, we
      photographed each patient. Fifteen healthy women served as control subjects. We
      used the percentage breast retraction assessment index (pBRA=BRA/reference length
      x 100) to compare cosmetic outcome. RESULTS: The median pBRAs of the ALND group
      and SN group (14.3 and 6.71, respectively) significantly differed ( p=0.001). The
      pBRA of the SN group was comparable to the pBRA (6.1) of the control group (
      p=0.317). CONCLUSION: Cosmetic outcome of BCT after the SN procedure was superior
      compared to the cosmetic outcome after ALND. This is an important additional
      reason to implement the SN procedure in routine daily practice.

PMID- 15986126
TI  - Antibiotic exposure and breast cancer in New Zealand.
AB  - Aims To investigate the hypothesis that use of antibiotics is related to
      subsequent development of breast cancer and also to apply this theory to other
      cancer types. Materials and methods A nested case-control study was conducted,
      using data linkage between the RNZCGP Research Unit database and the New Zealand
      Hospital Separation Diagnosis database. Cancer related hospital admissions were
      identified between 1998 and 2002, and prior antibiotic exposure in these patients
      was then found. Results A total of 6678 patients were identified with a newly
      diagnosed cancer in this time period. A slightly increased odds ratio (OR) (95%
      CI) for breast cancer was seen with penicillin, 1.07 (1.02-1.13). Penicillin was
      also associated with an increased OR with lung and respiratory cancer, 1.13 (1.06
      1.21), and skin neoplasms, 1.05 (1.02-1.08). Significant associations were seen
      between macrolides and leukaemia, 1.15 (1.01-1.30), lung and respiratory cancers,
      1.23 (1.10-1.38) and non-Hodgkin's lymphoma, 1.26 (1.02-1.55). Tetracyclines were
      significantly associated with non-Hodgkin's lymphoma, 1.12 (1.01-1.24).
      Cephalosporins only showed a significant association with leukaemia, 1.35 (1.06
      1.71), sulphonamides with colorectal cancers, 1.12 (1.01-1.24), and 'other'
      antibiotic classes with bladder and renal cancers, 1.34 (1.07-1.67). Conclusions
      It is most likely that antibiotic exposure represents a confounding factor rather
      than a causation for breast cancer and other cancer types.

PMID- 15986127
TI  - Sensitivity to further endocrine therapy is retained following progression on
      first-line fulvestrant.
AB  - There is a need for new endocrine agents that lack cross-resistance with
      currently available treatments to extend the endocrine treatment window and delay
      the need for cytotoxic chemotherapy. This retrospective analysis evaluated the
      response of postmenopausal patients with previously untreated metastatic/locally
      advanced breast cancer to further endocrine treatment following progression on
      first-line fulvestrant or tamoxifen. Patients received fulvestrant 250 mg
      (intramuscular injection every 28 days) plus matching tamoxifen placebo (once
      daily), or tamoxifen 20 mg (orally once daily) plus matching fulvestrant placebo
      (every 28 days) in a double-blind, randomized, phase III trial. Treatment
      continued until disease progression or withdrawal, when further endocrine therapy
      was initiated (at the treating physician's discretion). Information regarding
      subsequent therapies and responses was obtained by follow-up questionnaire. Two
      hundred-and-forty-five questionnaires were returned (from 587 patients), 149 of
      which yielded follow-up data on patients receiving second-line endocrine therapy
      following fulvestrant (n=83) and tamoxifen (n=66). Second-line therapy produced
      objective responses (OR) in 6/44 (13.6%) and clinical benefit (CB) in 25/44
      (56.8%) patients who had CB with fulvestrant and produced OR in 5/41 (12.2%)
      patients and CB in 27/41 (65.8%) patients who had CB with first-line tamoxifen.
      For patients deriving no CB from trial therapy, second-line therapy produced OR
      in 3/39 (7.7%) and CB in 15/39 (38.5%) patients in the fulvestrant group and OR
      in 4/25 (16.0%) and CB in 12/25 (48.0%) patients in the tamoxifen group. Results
      from this questionnaire-based study suggest that postmenopausal women with
      advanced breast cancer who respond to first-line fulvestrant or tamoxifen retain
      sensitivity to subsequent endocrine therapy.

PMID- 15986128
TI  - Somatostatin receptors in primary human breast cancer: quantitative analysis of
      mRNA for subtypes 1--5 and correlation with receptor protein expression and tumor
      pathology.
AB  - Somatostatin receptors (SSTRs) have been identified in most hormone-producing
      tumors as well as in breast cancer. In the present study, we determined SSTR1-5
      expression in primary ductal NOS breast tumors through semi-quantitative RT-PCR
      and immunocytochemistry. The results from the analysis of 98 samples were
      correlated with several key histological markers and receptor expression. All
      five SSTR subtypes are variably expressed at the mRNA level in breast tumors with
      91% of samples showing SSTR1, 98% SSTR2, 96% SSTR3, 76% SSTR4, and 54% SSTR5.
      SSTR1-5 are localized to both tumor cells and the surrounding peritumoral regions
      as detected by immunocytochemistry. Levels of SSTR mRNA, when corrected for beta
      actin levels, were highest for SSTR3 followed by SSTR1, SSTR2, SSTR5, and SSTR4.
      Furthermore, there was good correlation between mRNA and protein expression with
      84% for SSTR1, 79% for SSTR2, 89% for SSTR3, 68% for SSTR4, 68% for SSTR5, and
      78% for all five receptors. SSTR1, 2 and 4 were correlated with ER levels whereas
      SSTR2 showed an additional correlation with PR levels. These correlations were
      independent of patient age and histological grade. Moreover, using
      immunocytochemistry, blood vessels exhibited receptor-specific localization for
      SSTR2 and SSTR5. Our results indicate significant correlations between mRNA and
      protein expression along with receptor-specific correlations with histological
      markers as well as ER and PR levels. Differential distribution of SSTR subtypes
      in tumors and receptor-specific expression in vascular structures may be
      considered as a novel diagnosis for breast tumors with receptor subtype agonists.

PMID- 15986129
TI  - Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human
      breast cancer cells.
AB  - The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA), inhibit the growth of human breast cancer cells in animal models and cell
      lines, but the mechanism by which this occurs is not well understood. In order to
      explore possible mechanisms for the modulation of breast cancer cell growth by
      omega-3 fatty acids, we examined the effects of EPA and DHA on the human breast
      cancer cell line MDA-MB-231. Omega-3 fatty acids (a combination of EPA and DHA)
      inhibited the growth of MDA-MB-231 cells by 30-40% (p<0.05) in both the presence
      and absence of linoleic acid, an essential omega-6 fatty acid. When provided
      individually, DHA was more potent than EPA in inhibiting the growth of MDA-MB-231
      cells (p<0.05). EPA and DHA treatment decreased tumor cell proliferation
      (p<0.05), as estimated by decreased [methyl-(3)H]-thymidine uptake and expression
      of proliferation-associated proteins (proliferating cell nuclear antigen, PCNA,
      and proliferation-related kinase, PRK). In addition, EPA and DHA induced
      apoptosis, as indicated by a loss of mitochondrial membrane potential, increased
      caspase activity and increased DNA fragmentation (p<0.05). Cells incubated with
      omega-3 fatty acids demonstrated decreased Akt phosphorylation, as well as
      NFkappaB DNA binding activity (p<0.05). The results of this study indicate that
      omega-3 fatty acids decrease cell proliferation and induce apoptotic cell death
      in human breast cancer cells, possibly by decreasing signal transduction through
      the Akt/NFkappaB cell survival pathway.

PMID- 15986130
TI  - On cancer incidence in multiple sclerosis and effects of immunomodulatory
      treatments.

PMID- 15986131
TI  - Metastatic melanoma cells. Introduction.

PMID- 15986132
TI  - Integrin signaling in malignant melanoma.
AB  - Cell adhesion and migration are essential for embryonic development, tissue
      regeneration, but also for tumor development. The physical link between the
      extracellular matrix (ECM) and the actin cytoskeleton is mainly mediated by
      receptors of the integrin family. Through signals transduced upon integrin
      ligation to ECM proteins, this family of proteins plays key roles in regulating
      tumor growth and metastasis as well as tumor angiogenesis. During melanoma
      development, changes in integrin expression, intracellular control of integrin
      functions and signals perceived from integrin ligand binding impact upon the
      ability of tumor cells to interact with their environment and enable melanoma
      cells to convert from a sessile, stationary to a migratory and invasive
      phenotype. Antagonists of several integrins are now under evaluation in clinical
      trials to determine their potential as therapeutics for malignant melanoma and
      other kinds of cancer.

PMID- 15986133
TI  - Activated leukocyte cell adhesion molecule (ALCAM/CD166): signaling at the divide
      of melanoma cell clustering and cell migration?
AB  - Orchestrated modulation of cell adhesion is essential for development and
      homeostasis in multicellular organisms. It optimizes embedding of the cell in its
      dynamic environment and facilitates appropriate cell responses and intercellular
      communication. Chronic disturbance of this delicate equilibrium causes defects in
      tissue architecture and sometimes cancer. In tumor cell biology, dynamic control
      of adhesion molecules is important to proceed through the metastatic cascade and
      to allow cell release from the primary tumor, invasion of the surrounding matrix,
      intravasation and adhesion to vascular endothelial cells to facilitate
      extravasation. Intertwined and multiple adhesive interactions rather than
      individual interactions presumably play critical roles in neoplastic development.
      Yet, knowledge of the contribution of each individual adhesion molecule is
      essential to unravel this network of interactions. This review will focus on
      activated leukocyte cell adhesion molecule (ALCAM/CD166) and its role in human
      melanoma progression. It is hypothesized that ALCAM may function as a cell
      surface sensor to register local growth saturation and to regulate cellular
      signaling and dynamic responses.

PMID- 15986134
TI  - A Wnt-er wonderland--the complexity of Wnt signaling in melanoma.
AB  - Wnt signaling is a complex process that requires the interplay of several
      different proteins. In addition to a large cohort of Wnt ligands, and frizzled
      receptors, some Wnt pathways also require the presence of co-receptors. Wnt
      ligands may activate one of three pathways, the canonical pathway, involving beta
      -catenin, the planar cell polarity pathway and the Wnt/ calcium pathway. All
      three pathways have different results for the cells in which they signal.
      Aberrant activation of these pathways can lead to the development and progression
      of several cancers. In this review we will discuss the different Wnt pathways,
      and their contribution to melanoma progression.

PMID- 15986135
TI  - Bone morphogenetic proteins in melanoma: angel or devil?
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta (TGF-beta) superfamily serving multiple functions in many cell and tissue
      types including proliferation, apoptosis, differentiation, chemotaxis,
      angiogenesis, and matrix production during embryogenic development as well as in
      adult life. Despite the tremendous progress in delineating functional
      derangements of BMP pathways in carcinogenesis during the last decade, the
      biological significance of BMPs in human melanoma has received very little
      attention. It is now clear that biological responses to BMPs are cell type
      specific and divergent effects, i.e., both oncogenic and tumor suppressor
      activities, have been described. Thus, knowledge generated in one system may not
      translate directly to another. In this review, we summarize the current
      understanding of BMP signaling in various human cancers and discuss original data
      pertaining to cutaneous melanoma obtained in our laboratory.

PMID- 15986136
TI  - SKI pathways inducing progression of human melanoma.
AB  - The proteins SKI and SnoN are implicated in processes as diverse as
      differentiation, transformation and tumor progression. Until recently, SKI was
      solely viewed as a nuclear protein with a principal function of inhibiting TGF
      beta signaling through its association with the Smad proteins. However, new
      studies suggest that SKI plays additional roles not only inside but also outside
      the nucleus. In normal melanocytes and primary non-invasive melanomas, SKI
      localizes predominantly in the nucleus, whereas in primary invasive melanomas SKI
      displays both nuclear and cytoplasmic localization. Intriguingly, metastatic
      melanoma tumors display nuclear and cytoplasmic or predominantly cytoplasmic SKI
      distribution. Cytoplasmic SKI is functional, as it associates with Smad3 and
      prevents its nuclear localization mediated by TGF-beta. SKI can also function as
      a transcriptional activator, targeting the beta -catenin pathway and activating
      MITF and NrCAM, two proteins involved in survival, migration and invasion.
      Intriguingly, SKI appears to live a dual life, one as a tumor suppressor and
      another as a transforming protein. Loss of one copy of mouse ski increases
      susceptibility to tumorigenesis in mice, whereas its overexpression is associated
      with cancer progression of human melanoma, esophageal, breast and colon. The
      molecular reasons for such dramatic change in SKI function appear to result from
      new acquired activities. In this review, we discuss the mechanisms by which SKI
      regulates crucial pathways involved in the progression of human malignant
      melanoma.

PMID- 15986137
TI  - Functional and therapeutic significance of Akt deregulation in malignant
      melanoma.
AB  - Identification of specific genes or signaling pathways involved in development of
      melanoma could lead to new therapies that target and correct these defects.
      Recent studies have revealed deregulation of the Akt signaling pathway occurring
      in 43-67% of melanomas. Akt kinase family members, Akt1/PKBalpha, Akt2/PKBbeta
      and Akt3/PKBgamma, share extensive structural similarity and perform common as
      well as unique functions within cells. The Akt signaling cascade initiates at the
      cell surface when growth factors or other extracellular stimuli activate
      phosphoinositide 3-kinase (PI3K). Activated PI3K generates a lipid second
      messenger, phosphatidylinositol-3,4,5-trisphosphate (PIP3), causing translocation
      of Akt to the plasma membrane where it becomes phosphorylated and activated. The
      balance of cellular PIP3 is regulated primarily by a phosphatase called PTEN that
      reduces PIP3 levels thereby lowering Akt activity. In melanomas, decreased PTEN
      activity elevates PIP3 levels resulting in Akt activation. Active Akt then
      phosphorylates downstream cellular proteins that promote melanoma cell
      proliferation and survival. Recently, Akt3 was discovered to be the predominant
      isoform activated in sporadic melanomas. Levels of activity increased during
      melanoma progression with metastatic melanomas having the highest activity.
      Although mechanisms of Akt3 activation remain to be fully characterized,
      overexpression of Akt3 and decreased PTEN activity play important roles in this
      process. Targeted reduction of Akt3 activity decreased survival of melanoma tumor
      cells leading to inhibition of tumor development, which may be therapeutically
      effective for shrinking tumors in melanoma patients. This review surveys recent
      developments in Akt deregulation in melanoma and its potential as a selective
      therapeutic target in patients in the advanced stages of this disease.

PMID- 15986138
TI  - Protein kinase C in melanoma.
AB  - Protein kinase C (PKC) is activated by diacylglycerol generated by receptor
      mediated hydrolysis of membrane phospholipids to mediate signals for cell growth
      and plays as a target of tumor-promoting phorbol esters in malignant
      transformation. PKC is a family of enzymes and their expression profiles have
      been examined in the normal melanocytes and melanoma cells, and studies have been
      carried out on the functions of PKC isoforms in proliferation, transformation,
      and metastasis of melanoma cells. Here, we summarize current knowledge of the
      expression and possible roles of the PKC family in melanoma in comparison with
      those of normal melanocytes.

PMID- 15986140
TI  - Targeting STAT3 affects melanoma on multiple fronts.
AB  - As a point of convergence for numerous oncogenic signaling pathways, STAT3 is
      constitutively-activated at 50 to 90% frequency in diverse human cancers,
      including melanoma. A critical role of STAT3 in tumor cell survival,
      proliferation, angiogenesis, metastasis and immune evasion has been recently
      demonstrated. STAT3 contributes to tumor cell growth by regulating the expression
      of genes that are involved in cell survival and proliferation. STAT3 promotes
      metastasis and angiogenesis by inducing expression of the metastatic gene, MMP-2,
      and the potent angiogenic gene, VEGF. STAT3 participates in the regulation of
      tumor immune evasion by inhibiting expression of proinflammatory mediators while
      promoting expression of immune-suppressing factors, which in turn activates STAT3
      signaling in dendritic cells leading to immune tolerance. Thus, targeting STAT3
      for therapy assaults cancer on multiple fronts. Many of the studies that defined
      STAT3's role in oncogenesis were carried out in melanoma cells and tumor models.
      In this review, we summarize the key role of STAT3 in cancer in general and
      melanoma in particular. With the emergence of small-molecule drugs that directly
      inhibit STAT3 or the oncogenic signaling pathways upstream of STAT3 in melanoma,
      a promising novel approach for melanoma therapy is emerging.

PMID- 15986141
TI  - De-regulation of ubiquitin-dependent proteolysis and the pathogenesis of
      malignant melanoma.
AB  - Malignant melanoma is similar to the other types of cancer in terms that the
      pathogenesis of this lethal disease includes abnormal activation of proteins that
      mediate oncogenic signaling as well as inhibition of anti-proliferative and pro
      apoptotic protein regulators. Activity of both types of cellular regulators is
      often dependent on their abundance and is determined by the rate of proteolysis
      via the ubiquitin pathway. Aberrations in ubiquitin-dependent degradation of
      regulatory proteins frequently occur in human cancers including malignant
      melanoma. Melanoma cells that re-program ubiquitin-dependent proteolysis toward
      accelerated degradation of protein regulators of tumor suppression and abnormal
      stabilization of oncogenic proteins are likely to gain an advantage in growth and
      survival. Specific characteristics of melanoma biology include rapid
      metastasizing and resistance to conventional anticancer therapy. Exploration of
      these traits should place an emphasis on a subset of the signal transduction
      pathways that are governed by a number of key protein regulators whose stability
      and activity becomes deregulated during progression of malignant melanoma.
      Targeting the ubiquitination and degradation of these pivotal proteins may
      provide a promising new therapeutic approach to treatment of this disease.

PMID- 15986142
TI  - Rb/E2F: a two-edged sword in the melanocytic system.
AB  - Rb is a tumor suppressor that represses the expression of E2F regulated genes
      required for cell cycle progression. It is inactivated in melanomas and other
      cancer cells by phosphorylation catalyzed by persistent cyclin dependent kinase
      (CDK) activity. CDK activity is sustained in melanoma cells mostly by the
      elimination of the CDK inhibitor p16INK4A and by high levels of cyclins whose
      expression is maintained by stimuli emanating from activated cell surface
      receptors and/or mutated intracellular intermediates, such as N-Ras and B-Raf.
      However, Rb also suppresses the expression of apoptosis genes, and its presence
      protects normal melanocytes from cell death. Its high expression in human
      melanoma cells and tumors suggests a similar role in malignant cells as well. The
      differential release and suppression of E2F transcriptional activity is likely to
      depend on promoter-specific E2F/Rb interaction. Phosphorylated Rb is displaced
      from cell cycle genes but not from others. In addition, Rb gene repression is
      dependent on the nature of Rb-E2F interaction and the activity of the Rb-bound
      proteins recruited to the promoter. Deciphering the differences in Rb/E2F complex
      formation in normal and malignant melanocytes is likely to shed light on the
      mechanism by which Rb can exert tumor suppressing and promoting activities in
      this cellular system. The Rb/E2F pathway provides opportunities for efficient
      therapy at multiple levels. Novel drugs can reactivate Rb potential to suppress
      growth cycle promoting genes. In addition, the high E2F transcriptional activity
      in melanoma cells can be exploited to deliver cytotoxic molecules specifically to
      tumors, sparing the normal tissues.

PMID- 15986139
TI  - Role of nuclear factor-kappa B in melanoma.
AB  - Nuclear Factor-kappa B (NF-kappa B) is an inducible transcription factor that
      regulates the expression of many genes involved in the immune response. Recently,
      NF-kappa B activity has been shown to be upregulated in many cancers, including
      melanoma. Data indicate that the enhanced activation of NF-kappa B may be due to
      deregulations in upstream signaling pathways such as Ras/Raf, PI3K/Akt, and NIK.
      Multiple studies have shown that NF-kappa B is involved in the regulation of
      apoptosis, angiogenesis, and tumor cell invasion, all of which indicate the
      important role of NF-kappa B in tumorigenesis. Thus, understanding the molecular
      mechanism of melanoma progression will aid in designing new therapeutic
      approaches for melanoma. In this review, the association between NF-kappa B and
      melanoma tumorigenesis are discussed. Additionally, the potential of emerging
      selective NF-kappa B inhibitors for the treatment of melanoma is reviewed.

PMID- 15986143
TI  - Immunological detection of altered signaling molecules involved in melanoma
      development.
AB  - To understand immune responses to human cancer and develop more effective
      immunotherapy, human tumor antigens has been isolated using various immunological
      methods with tumor reactive T cells or antibodies obtained from patients with
      melanoma. During the process of tumor antigen isolation, various molecules with
      genetic alterations or over-expression in tumor cells, which may be involved in
      proliferation, differentiation, or survival of various cancer cells, were
      identified. In melanoma, abnormal molecules with mutations including beta 
      catenin, CDK4, and BRAF, and molecules with increased expression including
      Survivin, were immunologically detected. Therefore, immunological isolation of
      human tumor antigens contributes to the identification of important molecules
      including altered signaling molecules involved in melanoma formation.

PMID- 15986147
TI  - A new fluorescence resonance energy transfer pair and its application to
      oligonucleotide labeling and fluorescence resonance energy transfer hybridization
      studies.
AB  - We describe two new fluorescence resonance energy transfer (FRET) compatible
      labels, their covalent linkage to oligonucleotides, and their use as donor and
      acceptor, respectively, in FRET hybridization studies. The dyes belong to the
      cyanine dyes, and water solubility is imparted by a phosphonate which represents
      a new solubilizing group in DNA labels. They were linked to amino-modified
      synthetic oligonucleotides via oxysuccinimide (OSI) esters. The studies performed
      include binding assays, determinations of molecular distances, homogeneous
      competitive assays, and limits of detection, which are in the order of 5 pmol/L
      for a 15-mer.

PMID- 15986149
TI  - Dipyrrylmetheneboron difluorides as labels in two-photon excited fluorometry.
      Part I--Immunometric assays.
AB  - Seven different two-photon excitable dipyrrylmetheneboron difluoride labels
      (dipyrrylmethene-BF(2) labels) and a frequently used TAMRA label were conjugated
      to mouse IgG against alpha-fetoprotein in variable substitution degrees.
      Altogether 40 IgG conjugates were prepared, and studied with respect to one
      photon absorption and emission properties, and two-photon fluorescence efficiency
      using 1064 nm laser as illumination source. Performance of the IgG conjugates as
      tracers in a separation-free immunometric assay of alpha-fetoprotein was
      evaluated using two-photon excitation assay technology, ArcDia TPX. The results
      show that the dipyrrylmethene-BF(2) labels provide subpicomolar sensitivity,
      which is an order of magnitude better than that of TAMRA label. The effect of
      chromophore structure and substitution degree of IgG-label conjugates on the
      assay performance is discussed.

PMID- 15986148
TI  - Studies on the spectral-luminescent properties of the novel homodimer styryl dyes
      in complexes with DNA.
AB  - Series of homodimer styryls containing on (p-dimethylaminostyryl) pyridinium
      residues that are connected with aliphatic linkage group was synthesized.
      Spectral luminescent properties of obtained dyes in free state and in nucleic
      acids presence were studied. It was shown that DNA binding affinity of the novel
      homodimers exceeds that of parent monomer (p-dimethylaminostyryl)pyridine iodide.
      For homodimers with the linkage 4-10 carbon atoms preference in binding to DNA
      than to RNA was observed. It could be concluded that parent monomer has different
      mechanisms of binding to nucleic acids than corresponding homodimer dye.

PMID- 15986150
TI  - Dipyrrylmetheneboron difluorides as labels in two-photon excited fluorometry.
      Part II--Nucleic acid hybridization assays.
AB  - Five two-photon excitable dipyrrylmetheneboron difluoride labels (dipyrrylmethene
      BF(2) labels) with fluorescence emission maximum between 530 and 590 nm, and a
      frequently used rhodamine label, TAMRA, were conjugated to aminomodified
      oligonucleotides. The performance of the labeled oligonucleotides was studied in
      a separation-free nucleic acid hybridization assay using ArcDia TPX bioaffinity
      assay technology. The results show that oligonucleotide conjugates of
      dipyrrylmethene-BF(2) labels provide higher two-photon excited fluorescence yield
      and better assay sensitivity than corresponding TAMRA conjugate. The effect of
      conjugation on photophysical properties of the labels and performance of the
      labeled oligonucleotides in separation-free hybridization assay is discussed.

PMID- 15986151
TI  - Preparation and photophysics of 2-(1-pyrenyl)acrylic acid and its methyl and
      2',2',6',6'-tetramethyl-4'-piperidyl esters.
AB  - Novel probes represented connection of pyrene as chromophore and sterically
      hindered amine stabilizers (HAS) in the form of esters of 2-(1-pyrenyl)acrylic
      acid were synthesized. HAS was in the form of parent amine (PAP) as well as
      stable nitroxyl radical form (PAP-NO.). Photophysics of these probes were
      compared with their precursor as 2-(1-pyrenyl)acrylic acid (PAA) and its methyl
      ester (PAM). The fluorescence spectrum of PAA strongly depends on the acidity of
      the solution. The spectrum in neutral methanol indicates that it originates from
      the anionic form -COO(-). Changes of acidity or basicity of methanol solution
      resulted in the changes of shape, position as well as the intensity of
      fluorescence band. This is due to the presence of protolytic equilibria, either
      in the ground state or in the singlet excited state, leading to the formation of
      molecular form -COOH and the cationic form -COOH(2) (+). The ester analogues did
      not show any changes in various pH conditions. Fluorescence of all probes depends
      on the polarity of solvents and the presence of oxygen. Intermolecular quenching
      was studied with external quenchers TEMPO and oxygen and the data were compared
      with the intramolecular quenching using 1'-oxo-2',2',6',6'-tetramethyl-4'
      piperidinyl-2-(1-pyrenyl)acrylate (PAP-NO.).

PMID- 15986152
TI  - Rheofluorescence technique for the study of dilute MEH-PPV solutions in Couette
      flow.
AB  - A novel rheofluorescence technique has been developed that permits the study of
      fluorescent polymers in a near-uniform shear field. The system has been used to
      examine the effects of shear flow on dilute solutions of two commercially
      available samples of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]
      (MEH-PPV) in toluene and xylene. A detailed description of the instrument is
      provided, along with data that confirm a small probe molecule, Rhodamine 6G, is
      not affected by simple shear flow. MEH-PPV solutions were examined over two
      decades of concentration for rheochromism indicative of changes in segment
      length, and shear-induced orientation revealed by measurements of the steady
      state emission anisotropy. It is demonstrated that these dilute samples were not
      influenced by shear rates in the range 100-1000 s(-1). In contrast, MEH-PPV
      dispersed in a concentrated polystyrene solution showed evidence of shear-induced
      orientation and rheochromism. This new technique shows promise for investigating
      the impact of shear flow on the conformation of conjugated polymers employed in
      organic optoelectronic devices.

PMID- 15986153
TI  - New advances in fluorogenic anion chemosensors.
AB  - The development of anion chemosensors is an area of recent interest. We make here
      a comprehensive review of new advances on anion chemosensing, reported in the
      literature during the year 2004. The review follows a classification of the
      sensing systems based on design principles. It comprises: the binding site
      signalling subunit approach, the displacement approach and the use of fluoro
      chemodosimeters. The first two approximations are based on the use of a suitable
      anion coordination site coupled with a signalling unit which signals the anion
      coordination process via changes in its fluorescence behaviour. The two basic
      subunits are covalently linked in the binding site-signalling subunit approach
      and not in the displacement approach. In both approaches the fluorescence
      variation is reversible. The third way to the development of fluorogenic
      chemosensors is the use of chemodosimeters (also called reagents or reactands)
      that work usually through irreversible chemical reactions coupled with drastic
      changes in the fluorescence emission behaviour.

PMID- 15986155
TI  - Traceability in fluorometry--Part I: Physical standards.
AB  - The inter-instrument, inter-laboratory, and long-term comparability of
      fluorescence data requires the correction of the measured emission and excitation
      spectra for the wavelength- and polarization-dependent spectral irradiance of the
      excitation channel at the sample position and the spectral responsivity of the
      emission channel employing procedures that guarantee traceability to the
      respective primary standards. In this respect the traceability chain of
      fluorometry is discussed from a radiometrist's point of view. This involves, in a
      first step, the realization of the spectral radiance scale, based on the
      blackbody radiator and electron storage ring, and the spectral responsivity
      scale, based on the cryogenic radiometer and their control via key comparisons of
      the national metrology institutes. In a second step, the characterization
      including state-of-the art uncertainties of the respective source and detector
      transfer standards such as tungsten strip lamps, integrating sphere radiators,
      and trap detectors used to disseminate these radiometric quantities to users of
      spectroscopic techniques is presented.

PMID- 15986154
TI  - Fluorescent photoinduced electron transfer (PET) sensors for anions; from design
      to potential application.
AB  - This mini review highlights the synthesis and photophysical evaluation of anion
      sensors, for nonaqueous solutions, that have been developed in our laboratories
      over the last few years. We have focused our research mainly on developing
      fluorescent photoinduced electron transfer (PET) sensors based on the fluorophore
      spacer-anion receptor principle using several anthracene (emitting in the blue)
      and 1,8-naphthalimide (emitting in the green) fluorophores, with the aim of
      targeting biologically and industrially relevant anions such as acetates,
      phosphate and amino acids, as well as halides such as fluoride. The receptors and
      the fluorophore are separated by a short methyl or ethyl spacer, where the charge
      neutral anion receptors are either aliphatic or aromatic urea (or thiourea)
      moieties. For these, the anion recognition is through hydrogen bonding, yielding
      anion:receptor complexes. Such bonding gives rise to enhanced reduction potential
      in the receptor moieties which causes enhancement in the rate of PET quenching of
      the fluorophore excited state from the anion:receptor moiety. This design can be
      further elaborated on by incorporating either two fluorophores, or urea/thiourea
      receptors into the sensor structures, using anthracene as a fluorophore. For the
      latter design, the sensors were designed to achieve sensing of bis-anions, such
      as di-carboxylates or pyrophosphate, where the anion bridged the anthracene
      moiety. In the case of the naphthalimide based mono-receptor based PET sensors,
      it was discovered that in DMSO the sensors were also susceptible to deprotonation
      by anions such as F(-) at high concentrations. This led to substantial changes in
      the absorption spectra of these sensors, where the solution changed colour from
      yellow/green to deep blue, which was clearly visible to the naked eye. Hence,
      some of the examples presented can act as dual fluorescent-colorimetric sensors
      for anions. Further investigations into this phenomenon led to the development of
      simple colorimetric sensors for fluorides, which upon exposure to air, were shown
      to fix carbon dioxide as bicarbonate.

PMID- 15986156
TI  - Traceability in fluorometry: Part II. Spectral fluorescence standards.
AB  - The need for the traceable characterization of fluorescence instruments is
      emphasized from a chemist's point of view, focusing on spectral fluorescence
      standards for the determination of the wavelength- and polarization-dependent
      relative spectral responsivity and relative spectral irradiance of fluorescence
      measuring systems, respectively. In a first step, major sources of error of
      fluorescence measurements and instrument calibration are revealed to underline
      the importance of this issue and to illustrate advantages and disadvantages of
      physical and chemical transfer standards for generation of spectral correction
      curves. Secondly, examples for sets of traceable chemical emission and excitation
      standards are shown that cover a broad spectral region and simple procedures for
      the determination of corrected emission spectra with acceptable uncertainties are
      presented. With proper consideration of the respective measurement principle and
      geometry, these dye-based characterization procedures can be not only applied to
      spectrofluorometers but also to other types of fluorescence measuring systems and
      even to Raman spectrometers.

PMID- 15986158
TI  - Performance validation for microplate fluorimeters.
AB  - As the sophistication of instruments that make fluorimetric measurements on
      samples in microplates has increased, so has the need for methods to validate
      instrumental performance. This paper describes a solid-state validation
      microplate that tests multiple aspects of fluorescence performance, including
      signal linearity, gain, noise, sensitivity, wavelength accuracy, and polarization
      stability. Both the operating principles and the validation of the validation
      microplate are discussed.

PMID- 15986157
TI  - How to improve quality assurance in fluorometry: fluorescence-inherent sources of
      error and suited fluorescence standards.
AB  - The scope of this paper is to illustrate the need for an improved quality
      assurance in fluorometry. For this purpose, instrumental sources of error and
      their influences on the reliability and comparability of fluorescence data are
      highlighted for frequently used photoluminescence techniques ranging from
      conventional macro- and microfluorometry over fluorescence microscopy and flow
      cytometry to microarray technology as well as in vivo fluorescence imaging.
      Particularly, the need for and requirements on fluorescence standards for the
      characterization and performance validation of fluorescence instruments, to
      enhance the comparability of fluorescence data, and to enable quantitative
      fluorescence analysis are discussed. Special emphasis is dedicated to spectral
      fluorescence standards and fluorescence intensity standards.

PMID- 15986159
TI  - Pitfalls and their remedies in time-resolved fluorescence spectroscopy and
      microscopy.
AB  - Time-resolved fluorescence spectroscopy and microscopy in both time and frequency
      domains provide very useful and accurate information on dynamic processes. Good
      quality data are essential in obtaining reliable parameter estimates. Distortions
      of the fluorescence response due to artifacts may have disastrous consequences.
      We provide here a concise overview of potential difficulties encountered under
      daily laboratory circumstances in the use of time- and frequency-domain equipment
      as well as practical remedies against common error conditions, elucidated with
      several graphs to aid the researcher in visual inspection and quality-control of
      collected data. A range of artifacts due to sample preparation or to optical and
      electronic pitfalls are discussed, as are remedies against them. Also recommended
      data analysis strategies are described.

PMID- 15986160
TI  - Statistical analysis of diffusion coefficient determination by fluorescence
      correlation spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) has become an important and widely
      used technique for many applications in physics, chemistry, and biology. The
      parameter most frequently addressed by FCS is the diffusion of molecules in
      solution. Due to the highly non-linear connection between the diffusion
      coefficient and a measured autocorrelation function, it is extremely difficult to
      analyse the accuracy of the diffusion-coefficient determination in a FCS
      experiment. Here, we present a simplified analysis based on some general maximum
      likelihood considerations, and numerical result are given for the dependence of
      the accuracy of the diffusion-coefficient determination on sample concentration,
      brightness, and measurement time. Optimal concentration values for performing FCS
      are found.

PMID- 15986161
TI  - Improved routine bio-medical and bio-analytical online fluorescence measurements
      using fluorescence lifetime resolution.
AB  - Fluorescence techniques are widely used as sensitive detection methods in bio
      analytics. The use of the bio-physical parameter fluorescence lifetime additional
      to the spectral characteristics of fluorescence has the potential to improve
      fluorescence-related detection methods in terms of selectivity in signal
      recognition, robustness against disturbing influences, and the accessibility of
      novel bio-chemical process parameters. This article describes the technical set
      up of a time-resolving instrument with either a fixed time-gated detection
      principle for improved evaluation of tissue metabolism by an online monitoring of
      the tissue autofluorescence or a direct fluorescence lifetime detection principle
      for lifetime-based fluorescent assays.

PMID- 15986162
TI  - Concept for the traceability of fluorescence (beads) in flow cytometry:
      exploiting saturation and microscopic single molecule bleaching.
AB  - We have determined the fluorescence yield of stained micro beads, used for
      calibration purposes in flow cytometry, as function of the irradiance of the
      exciting laser beam. A rate equation model has been applied to derive the number
      of fluorescence molecules carried by each micro bead. To derive in situ photo
      physical properties of the specific dye, required for the rate equation model, we
      discuss an approach based on flow cytometric sorting of micro beads, which have
      passed two laser beams with properly chosen different irradiances, and subsequent
      observation of single molecule bleaching employing high sensitivity microscopy.
      The feasibility of our approach is demonstrated presenting first results
      concerning saturation of fluorescence of beads in flow and single molecule
      bleaching by high sensitivity microscopy.

PMID- 15986163
TI  - Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging.
AB  - Optical technologies are evolving in many biomedical areas including the
      biomedical imaging disciplines. Regarding the absorption properties of
      physiological molecules in living tissue, the optical window ranging from 700 to
      900 nm allows to use fluorescent dyes for novel diagnostic solutions. Here we
      investigate the potential of two different carbocyanine-based dyes fluorescent in
      the near infrared as contrast agents for in vivo imaging of subcutaneously grown
      tumours in laboratory animals. The primary aim was to modify the physicochemical
      properties of the previously synthesized dye SIDAG to investigate the effect on
      the in vivo imaging properties.

PMID- 15986169
TI  - Persistence of invertebrate iridescent virus 6 in tropical artificial aquatic
      environments. Brief report.
AB  - The rate of loss of activity of invertebrate iridescent virus 6 (IIV-6, family
      Iridoviridae) was determined in two artificial aquatic habitats in southern
      Mexico, using a sensitive insect bioassay technique. IIV-6 placed in trays of
      water in direct sunlight suffered rapid loss of activity (99.99% reduction) over
      a period of 36 h, during which water temperatures fluctuated between 24 and 41
      degrees C. No significant deactivation occurred during the hours of darkness. In
      contrast, IIV-6 placed in trays of water in the shade lost 97% of original
      activity over a 60 h period, during which water temperatures fluctuated from 24
      to 31 degrees C. Longitudinal analysis involving mixed effects models of time
      (shade) and cumulative exposure to ultraviolet radiation (sunlight) indicated
      that the rate of deactivation was best described by third order polynomial
      equations in both cases. We conclude that the likelihood of transmission of IIVs
      in aquatic habitats will be mediated by the intensity of UV radiation and water
      temperature.

PMID- 15986170
TI  - The complete sequence of a Spanish isolate of Broad bean wilt virus 1 (BBWV-1)
      reveals a high variability and conserved motifs in the genus Fabavirus.
AB  - The genome of a Spanish isolate of Broad bean wilt virus-1 (BBWV-1) was
      completely sequenced and compared with available sequences of other isolates of
      the genus Fabavirus (BBWV-1 and BBWV-2). This consisted of two RNAs of 5814 and
      3431 nucleotides, respectively, and their organization was similar to that of
      other members of the family Comoviridae. Its mean nucleotide identity with a BBWV
      1 American isolate was 81.5%, and between 59.8 and 63.5% with seven BBWV-2
      isolates. Our analysis showed sequence stretches in the 5' non-coding regions
      which are conserved in both genomic RNAs and in BBWV-1 and BBWV-2 isolates.

PMID- 15986171
TI  - Changing circulation rate of human metapneumovirus strains and types among
      hospitalized pediatric patients during three consecutive winter-spring seasons.
      Brief report.
AB  - From 2001 through 2004, 808 pediatric patients admitted to hospital because of
      acute respiratory infections were examined for presence of respiratory viruses by
      either direct fluorescent staining using monoclonal antibodies or RT-PCR during
      three consecutive winter-spring seasons. On the whole, 336 (42%) patients were
      detected as positive for one or more respiratory viruses. The most widely
      circulating virus was human respiratory syncytial virus (hRSV) infecting 50% of
      positive patients, followed by human metapneumovirus (hMPV) found in 13% of
      patients, and then by influenza virus type A, human parainfluenzaviruses and
      coinfections. Significant variations in the circulation rate of hRSV, hMPV and
      influenzavirus type A were observed during the individual seasons. In addition,
      the circulation rates of the different types of hMPV changed yearly. In 2001-2002
      and 2002-2003 hMPV circulated at a significant lower proportion than hRSV, while
      in 2003-2004 the circulation rates of the two viruses were closer. In conclusion,
      the 4 hMPV subtypes circulated yearly in Northern Italy flanking hRSV as major
      respiratory pathogens in the infantile patient population.

PMID- 15986172
TI  - Identification of a second begomovirus, Sri Lankan cassava mosaic virus, causing
      cassava mosaic disease in India.
AB  - The DNA A and DNA B components of a begomovirus associated with cassava mosaic
      disease (CMD) originating from Kerala, India, were cloned. Biolistically
      inoculated clones induced symptoms typical of CMD in cassava. Sequence
      comparisons showed the virus to be an isolate of Sri Lankan cassava mosaic virus
      (SLCMV). This is the first time this begomovirus species has been identified in
      India and only the second species shown to cause CMD in the country. The
      implication of these findings on our understanding of the diversity and
      geographic distribution of CMD-associated begomoviruses in the region and on
      efforts to obtain resistance to CMD are discussed.

PMID- 15986173
TI  - Complete nucleotide sequence of the new potexvirus "Alstroemeria virus X". Brief
      report.
AB  - A flexuous virus was isolated in Japan from an alstroemeria plant showing mosaic
      symptoms. The virus had a broad host range but had systemically latent
      infectivity in alstroemeria. The virus was assigned to the genus Potexvirus based
      on morphology and physical properties and on an analysis of the complete
      nucleotide sequence. The genomic RNA of the virus was 7,009 nucleotides in
      length, excluding the 3'-terminal poly (A) tail. It contained five open reading
      frames (ORFs), which was consistent with other members of the genus Potexvirus.
      Although nucleotide sequences of the ORFs differ from previously reported
      potexviruses, a phylogenetic analysis placed it phylogenetically close to
      Narcissus mosaic virus and Scallion virus X. Therefore, we propose that this
      virus should be designated as Alstroemeria virus X (AlsVX).

PMID- 15986174
TI  - Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus
      from patients with pneumonia.
AB  - Phylogenetic trees constructed using predicted amino acid sequences of putative
      proteins of coronavirus HKU1 (CoV-HKU1) revealed that CoV-HKU1 formed a distinct
      branch among group 2 coronaviruses. Of the 14 trees from p65 to nsp10, nine
      showed that CoV-HKU1 was clustered with murine hepatitis virus. From nsp11, the
      topologies of the trees changed dramatically. For the eight trees from nsp11 to
      N, seven showed that the CoV-HKU1 branch was the first branch. The codon usage
      patterns of CoV-HKU1 differed significantly from those in other group 2
      coronaviruses. Split decomposition analysis revealed that recombination events
      had occurred between CoV-HKU1 and other coronaviruses.

PMID- 15986175
TI  - Dimerization of glycoprotein E(rns) of classical swine fever virus is not
      essential for viral replication and infection.
AB  - The pestivirus glycoprotein E(rns), a ribonuclease, is expressed on the surface
      of virions and in infected cells as a disulfide-linked homodimer. E(rns) is
      involved in the infection process and its RNase activity is probably involved in
      viral replication and pathogenesis. The most C-terminal cysteine residue forms an
      intermolecular disulfide bond with another E(rns) monomer, resulting in an E(rns)
      dimer. To study the function of dimerisation of E(rns) for viral replication, the
      cysteine residue at amino acid position 438 was mutated into a serine residue.
      The mutated C438S gene was cloned into a vector containing an infectious cDNA
      copy of the CSFV C-strain genome. Using reverse genetics, a mutant virus was
      generated that only expressed monomeric E(rns), confirming that Cys 438 is
      essential for homo-dimerization. Characterization of this mutant virus and of a
      baculovirus-expressed C438S mutant protein indicated that the loss of the dimeric
      state of E(rns) reduced the affinity of binding of virions and E(rns) to heparan
      sulphate (HS), the receptor for E(rns) on the cell surface of SK6 cells. This
      suggests that interaction of virus-bound E(rns) homodimers with membrane
      associated HS may be a joined action of the two HS-binding domains (one in each
      monomer) present in the homodimer.

PMID- 15986176
TI  - Stachytarpheta leaf curl virus is a novel monopartite begomovirus species.
AB  - Begomovirus isolates were obtained from Stachytarpheta jamaicensis plants showing
      leaf curl and chlorosis symptoms collected in the Hainan province of China. The
      complete sequences of isolates Hn5-4, Hn6-1, Hn30 and Hn34 were determined to be
      2748, 2751, 2748 and 2748 nucleotides long, respectively. The complete sequences
      of the four isolates share more than 94.9% nucleotide sequence identity, but all
      of them have less than 86% nucleotide sequence identity with other reported
      begomoviruses. The molecular data show that Hn5-4, Hn6-1, Hn30 and Hn34 are
      isolates of a distinct begomovirus species, for which the name Stachytarpheta
      leaf curl virus (StaLCV) is proposed. PCR and Southern blot analyses demonstrate
      that all the collected field samples are not associated with DNAbeta or DNA-B
      components. An infectious clone of StaLCV isolate Hn5-4 was constructed, and
      could efficiently infect Nicotiana benthamiana, N. tabacum Samsun, N. glutinosa,
      Lycopersicon esculentum and Petunia hybrida plants, inducing upward leaf roll and
      vein swelling symptoms. In addition, we illustrate that StaLCV can functionally
      interact with distinct DNAbeta molecules in plants.

PMID- 15986177
TI  - Circulating leukocyte and cytokine responses to measles and poliovirus
      vaccination in children after ultraviolet radiation exposures.
AB  - Suberythemal ultraviolet radiation (UVR) exposures of children are used routinely
      in Russia to prevent rickets and to strengthen general health. The aim of the
      present study was to re-evaluate the effects of such a regime on immune responses
      as UVR is now recognised to suppress cell-mediated immunity in many animal
      models. Seventeen infants were immunised with attenuated measles and recall polio
      vaccines of whom 10 had been given a course of prophylactic UV exposures before
      the vaccinations. All the infants in the study developed an acute infectious
      conjunctivitis one week prior to the vaccinations and were convalescent at the
      time of the vaccination. They were bled on the day of the vaccinations and at
      several times thereafter to assess leukocyte percentages and plasma cytokine
      levels. On the day of the vaccinations, an active immune response was apparent.
      The UV-exposed children differed from the unexposed children by having a smaller
      percentage of natural killer cells and a higher percentage of CD25-positive
      cells. In the days following the vaccinations, the UV-exposed infants had a
      lowered percentage of total lymphocytes with increased percentages of monocytes,
      eosinophils, neutrophils and HLA-DR-positive cells as well as higher
      concentrations of plasma IL-1beta and IL-10 compared with the unexposed infants.
      There were no local or systemic clinical reactions to the vaccines in the UV
      group while a moderate rise in temperature of three children in the unexposed
      group occurred. Thus the UV irradiations modulated leukocyte percentages and
      plasma cytokine levels following the vaccinations, perhaps through the activation
      of a T helper 2-like response.

PMID- 15986178
TI  - Telomere size and telomerase activity in Epstein-Barr virus (EBV)-positive and
      EBV-negative Burkitt's lymphoma cell lines.
AB  - The telomere repeat lengths of BL cell lines were quantified by measuring
      terminal restriction fragment (TRF). Epstein-Barr virus (EBV)-positive Namalwa,
      Raji, and EB-3 cell lines have long telomeres, i.e. TRFs 10-19 kbp, whereas the
      Daudi cell line, producing a transformation-defective EBV mutant, has TRFs
      approximately 2.2 kbp. EBV-negative BJAB and DG75 cell lines have short TRFs 3.9
      5.4 kbp, shorter than the approximately 12 kbp TRFs in PBLs. Telomerase
      activities of these BL cell lines are similar. TRFs of non-BL lymphoma cell lines
      are 2.3-5.5 kbp. Fluorescent in situ hybridization (FISH) studies of these cell
      lines showed remarkable heterogeneity of telomere size in chromosomes in the same
      BL cell. These results suggest that EBV-positive and EBV-negative BL cell lines
      have experienced various telomere dynamics.

PMID- 15986179
TI  - Characterization of the nucleic acid binding activity of inner core protein VP6
      of African horse sickness virus.
AB  - Minor structural protein VP6 is the putative helicase of African horse sickness
      virus (AHSV), of the genus Orbivirus in the Reoviridae family. We investigated
      how the protein interacts with double-stranded (ds) RNA and other nucleic acids.
      Binding was assayed using an electrophoretic migration retardation assay and a
      nucleic acid overlay protein blot assay. VP6 bound double and single stranded RNA
      and DNA in a NaCl concentration sensitive reaction. Of six truncated VP6 peptides
      investigated, two partially overlapping peptides were found to bind dsRNA at pH
      7.0, while other peptides with the same overlap did not. The distinction between
      the peptides appeared to be the pI which ranged from more than 8.0 to just above
      6.0. Changing the pH of the binding buffer modified the binding activity.
      Regardless of assay conditions, only peptides with a specific region of amino
      acids in common, showed evidence of binding activity. No sequence homology was
      identified with other binding domains, however, the presence of charged amino
      acids are assumed to be important for binding activity. The results suggested
      dsRNA binding in the blot assay was strongly affected by the net charge on the
      peptide.

PMID- 15986180
TI  - The neuronal differentiation process involves a series of antioxidant proteins.
AB  - Involvement of individual antioxidant proteins (AOXP) and antioxidants in the
      differentiation process has been already reported. A systematic search strategy
      for detecting differentially regulated AOXP in neuronal differentiation, however,
      has not been published so far. The aim of this study was to provide an analytical
      tool identifying AOXP and to generate a differentiation-related AOXP expressional
      pattern. The undifferentiated N1E-115 neuroblastoma cell line was switched into a
      neuronal phenotype by DMSO treatment and used for proteomic experiments: We used
      two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical
      (MALDI-TOF-TOF) identification of proteins to generate a map of AOXP. 16 AOXP
      were unambiguously determined in both cell lines; catalase, thioredoxin domain
      containing protein 4 and hypothetical glutaredoxin/glutathione S-transferase C
      terminus-containing protein were detectable in the undifferentiated cells only.
      Five AOXP were observed in both, undifferentiated and differentiated cells and
      thioredoxin, thioredoxin-like protein p19, thioredoxin reductase 1, superoxide
      dismutases (Mn and Cu-Zn), glutathione synthetase, glutathione S-transferase P1
      and Mu1 were detected in differentiated cells exclusively. Herein a differential
      expressional pattern is presented that reveals so far unpublished antioxidant
      principles involved in neuronal differentiation by a protein chemical approach,
      unambiguously identifying AOXP. This finding not only shows concomitant
      determination of AOXP but also serves as an analytical tool and forms the basis
      for design of future studies addressing AOXP and differentiation per se.

PMID- 15986181
TI  - Alicyclic beta-amino acids in Medicinal Chemistry.
AB  - The structural element of alicyclic beta-amino acids shows some remarkable
      biological effects: For some 5- and 6-membered beta-amino acids a unique anti
      fungal activity has been observed, 7-membered beta-amino acid derivatives have
      been investigated for neurological disorders. The application of 5-, 6- and 7
      membered alicyclic beta-amino acids in Medicinal Chemistry will be reported.
      [structure: see text]

PMID- 15986182
TI  - Clinical characteristics of pelvic fracture patients with gluteal necrosis
      resulting from transcatheter arterial embolization.
AB  - BACKGROUND: Transcatheter arterial embolization (TAE) can cause gluteal skin and
      muscle necrosis. However, the ultimate and typical signs of gluteal necrosis
      resulting from TAE have not yet thoroughly been investigated. METHODS: From
      January 1995 to December 2003, 165 pelvic fractures were managed with TAE to
      control retroperitoneal bleeding at our level 1 trauma center. From these, 12
      patients suffered gluteal muscle and skin necrosis. We reviewed the medical
      records of these 12 patients for age, gender, fracture type, embolic sites,
      computed tomography (CT) findings, serum creatine kinase level, site of skin
      necrosis, time from injury to skin necrosis, treatment, and outcome. RESULTS: All
      12 patients underwent TAE of the bilateral internal iliac arteries with gelatin
      sponge slurries. One patient suffered from an infection of the gluteal muscle
      from an open fracture site. Five patients presented with signs of gluteal soft
      tissue injuries on admission. Of these, four had skin abrasions and three
      revealed fluid or air collection under the gluteal skin on CT. The remaining six
      patients showed no evidence of soft tissue injuries on admission, and the lesions
      appeared between 2 days and 7 days after their admission. In these six patients,
      low-density areas (LDAs) of gluteal muscle with a clear border on the CT were
      observed following the appearance of skin lesion. The skin necrosis was located
      in the center of either or both buttocks, and signs of ischemia were clearly
      demarcated from the adjacent normal tissue. Four of 12 patients died from sepsis,
      three of whom suffered from uncontrollable gluteal infections that had been
      pointed out as LDAs on the CT. CONCLUSIONS: In every patient with gluteal
      necrosis associated with pelvic fracture following TAE, initial traumatic
      contusion cannot be ruled out as contributing to the development of the necrosis.
      However, for patients who undergo TAE of the bilateral internal iliac artery and
      who show clear-border LDAs on CT, skin necrosis centered on the buttock, and the
      delayed appearance of a skin lesion, careful attention must be given in the event
      of an arterial obstruction due to TAE.

PMID- 15986183
TI  - [Early transfer from intensive care does not influence clinical results of
      carotid endarterectomy].
AB  - The purpose of this prospective observational study was to examine the necessity
      of intensive care after carotid endarterectomy (CEA). In consideration of the
      neurological stage and comorbidities, morbidity and mortality after early
      transfer from the intensive care unit (ICU) were examined. The CEA patients were
      assigned preoperatively to short or long monitoring. Those with symptomatic
      stenosis ranking > or =2 (stroke within 6 weeks before surgery) and ischemic
      areas in cCT were observed overnight (long) in the ICU. Within 5.5 months, 100
      consecutive patients had received 107 CEAs. Preoperatively, seven of these
      (6.54%) were assigned to ICU overnight monitoring. 14 patients (13%) needed
      postoperative over night ICU. We observed no perioperative stroke or mortality in
      the 107 consecutive CEAs. We could not detect any risk factor in preoperatively
      determining the length of postoperative ICU monitoring. This prospective, single
      center study showed that, after CEA, it is safe to monitor patients for only a
      short period (4-8 h) in the ICU. Morbidity and mortality after early transfer to
      the regular ward did not increase.

PMID- 15986184
TI  - Paraneoplastic syndromes in patients with primary malignancies of the head and
      neck. Four cases and a review of the literature.
AB  - Paraneoplastic syndromes rarely affect patients with head and neck cancer. Four
      patients with different histological types of head and neck cancer are presented
      in which the primary malignancy was preceded and/or accompanied by a
      paraneoplastic syndrome. In the first patient erythrodermia preceded the
      diagnosis of a nasopharyngeal carcinoma. The second patient presented with a B
      cell lymphoma of the nasopharynx in association with the syndrome of
      inappropriate secretion of arginine vasopressine (Schwartz-Bartter syndrome). In
      the third patient paraneoplastic polyarthritis had been diagnosed 5 months before
      a hypopharyngeal carcinoma was diagnosed. In the last patient the paraneoplastic
      anti-Hu positive encephalomyelitis was associated with a primary malignancy in
      the larynx with neck metastases. Diagnostic procedures, treatment and follow-up
      of these patients are reported and accompanied by a review of the literature.

PMID- 15986186
TI  - A proof-of-concept study using [11C]flumazenil PET to demonstrate that pagoclone
      is a partial agonist.

PMID- 15986185
TI  - Effects of subchronic methamphetamine exposure on basal dopamine and stress
      induced dopamine release in the nucleus accumbens shell of rats.
AB  - RATIONALE: Subchronic administration of stimulants reduces basal dopamine (DA)
      concentrations and blocks stress-induced DA release in the nucleus accumbens (NA)
      of rats during withdrawal. However, no studies have attempted to relate early
      withdrawal from chronic drug exposure to stress reactivity and changes in DA
      transmission. OBJECTIVES: The effects of subchronic low-dose methamphetamine
      (METH) administration on regional changes in dopamine transporter (DAT) and
      norepinephrine transporter (NET) immunoreactivity and function during early
      withdrawal were examined. The effects of subchronic METH on stress responsivity
      measured by DA release in the nucleus accumbens shell (NA SHELL) and core (NA
      CORE) during acute restraint stress were also examined. METHODS: Male rats
      received single injections of METH (2.0 mg/kg i.p.) or saline (SAL) for 10 days
      and then were killed 24 h after the last injection. DAT and NET protein in NA,
      striatum (STR), medial prefrontal cortex (mPFC), and hippocampus were assayed by
      Western blot analysis. Experiment 2 measured basal extracellular DA
      concentrations and restraint-stress-induced DA release in vivo in the NA SHELL
      and CORE of SAL- and METH-pretreated rats after 24-h withdrawal. Experiment 3
      examined the in vivo regulation of extracellular DA in the NA SHELL and/or CORE
      after local administration of GBR12909 (50 microM) or nisoxetine (100 microM; NA
      SHELL). RESULTS: Subchronic METH increased DAT but not NET immunoreactivity in
      the NA compared to the STR and mPFC. METH reduced basal extracellular DA and
      blocked restraint-stress-induced DA release in the NA SHELL. DA uptake blockade
      increased extracellular DA more in the NA SHELL of METH rats, whereas NE uptake
      blockade increased basal DA concentrations to a similar extent in METH and SAL
      rats. CONCLUSIONS: These results suggest that subchronic METH exposure
      selectively increases NA DAT and consequently reduces basal and stress-induced DA
      release in the NA SHELL during early withdrawal.

PMID- 15986187
TI  - Chronic valproate does not alter the kinetics of docosahexaenoic acid within
      brain phospholipids of the unanesthetized rat.
AB  - RATIONALE: It has been reported that each of three drugs effective in treating
      bipolar disorder (lithium, carbamazepine, and valproate) decreases the turnover
      of arachidonic acid (AA, 20:4n-6) in brain phospholipids of the awake rat. It is
      also known that lithium and carbamazepine do so without decreasing the turnover
      of docosahexaenoic acid (DHA, 22:6n-3). OBJECTIVE: The aim of this study was to
      see whether valproate also specifically targets the turnover of AA but not of DHA
      in brain phospholipids. METHODS: Valproate was administered (200 mg kg(-1), i.p.)
      to rats for 30 days to produce a therapeutically relevant plasma concentration
      and then determine its effect compared with that of vehicle on incorporation and
      turnover rates of DHA in brain phospholipids. In unanesthetized rats that had
      received valproate or vehicle, [1-14C]DHA was infused intravenously, and arterial
      blood plasma was sampled until the animal was killed at 5 min; and its brain,
      after being microwaved, was subjected to chemical and radiotracer analysis.
      RESULTS: Using equations derived from our fatty acid model, it was found that
      chronic valproate compared with vehicle did not alter the rate of incorporation
      or turnover of DHA in brain phospholipids. Valproate-treated animals had higher
      concentrations of linoleic acid (18:2n-6) in several brain phospholipids,
      supporting the hypothesis that it alters brain n-6 fatty acid metabolism.
      CONCLUSIONS: The results, comparable to published findings following chronic
      administration of lithium and carbamazepine to rats, support the hypothesis that
      drugs are effective against mania in bipolar disorder act by downregulating
      incorporation and turnover of AA, but not of DHA, in brain phospholipids.

PMID- 15986188
TI  - Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor
      antagonist GR205171 in impulsive-related behaviour in rats.
AB  - RATIONALE: Substance P receptor [neurokinin1 (NK1-R)] antagonists and
      melatonin(1/2) receptor (MT(1/2)-R) agonists have been claimed to be potential
      antidepressants (ADs). In animals, these compounds are active in validated models
      responsive to ADs, such as forced swimming test and chronic mild stress
      paradigms. Classical AD drugs are also known to be effective in pathologies
      characterized by an impulse control deficiency. In line with this clinical
      observation, previous studies demonstrated that classical ADs increased the
      capacity to wait for food reward in rats subjected to a paradigm aimed at
      assessing impulsive-related behaviour. OBJECTIVES: This study was conducted to
      investigate the effects of two MT(1/2)-R agonists, melatonin and agomelatine, and
      a NK1-R antagonist, GR205171, on tolerance to delay of food reward in rats.
      METHODS: Fasting rats were trained in a T-maze and allowed to choose between two
      magnitudes of reward: immediate but small reward (two pellets) vs 25-s delayed
      but large reward (ten pellets). Under this alternative, vehicle-injected rats
      selected the large-but-delayed reinforcer in less than 40% of the trials.
      RESULTS: Like the established ADs clomipramine (8 mg kg(-1), i.p.) and
      fluvoxamine (4 mg kg(-1), i.p.), melatonin (3 and 10 mg kg(-1), i.p.),
      agomelatine (10 and 30 mg kg(-1), i.p.) and GR205171 (30 mg kg(-1) but not 10 mg
      kg(-1), s.c.) significantly increased the number of choices of the large-but
      delayed reward. The effect of melatonin (3 mg kg(-1), i.p.) was not counteracted
      by the MT(1/2)-R antagonist S22153 (40 mg kg(-1), i.p.) that exerted no effect on
      its own. CONCLUSION: These results suggest that MT(1/2)-R agonists and NK1-R
      antagonists enhance rats' tolerance to delay of gratification, an effect which
      may reflect their ability to improve impulse control. Further investigations are
      necessary to clarify the neurobiological mechanisms responsible for this effect.

PMID- 15986189
TI  - Association study of a novel functional polymorphism of the serotonin transporter
      gene in bipolar disorder and suicidal behaviour.
AB  - A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been
      investigated in several genetic association studies, including studies of bipolar
      disorder (BD) and suicidality. The current study was designed to examine whether
      the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with
      the suicide attempts in 305 families with at least one member having BD. No
      association with history of suicide attempt was found either in the multiallelic
      HTTLPR (LRS=0.15, df=2, P=0.92), or with the intron 2 variable number tandem
      repeat (VNTR) polymorphism (LRS=0.87 df=2 P=0.64). When we performed a haplotype
      analysis, we found no association between suicide attempt and haplotype
      distribution (LRS=1.84 df=4 P=0.76). These findings suggest that this new
      polymorphism in the 5-HTT gene may not influence suicidal behaviour in patients
      with bipolar disorder.

PMID- 15986190
TI  - Platelet monoamine oxidase in alcoholism.

PMID- 15986191
TI  - Reinforcing effects of modafinil: influence of dose and behavioral demands
      following drug administration.
AB  - RATIONALE: The reinforcing effects of stimulant drugs are modulated by behavioral
      demands following drug administration. OBJECTIVE: The objective of this study was
      to assess the reinforcing effects of modafinil, a drug with purportedly low abuse
      potential, under different behavioral demands using a modified progressive-ratio
      procedure. METHODS: The reinforcing effects of oral modafinil (0, 100, 200, and
      400 mg) were assessed in six healthy adult volunteers under both performance and
      relaxation conditions. Performance sessions required volunteers to complete
      simple arithmetic problems for three 50-min blocks. Relaxation sessions required
      volunteers to sit quietly in a semi-reclined position in a darkened room for
      three 50-min blocks. Two sampling sessions (one performance and one relaxation
      session) always preceded two self-administration sessions (one performance and
      one relaxation session), and the order of performance and relaxation sessions was
      constant within a dose condition. RESULTS: Modafinil significantly increased
      break point and number of capsules earned on the modified progressive-ratio
      procedure as an increasing function of dose under the performance, but not the
      relaxation, condition. Modafinil produced comparable stimulant-like subjective
      ratings under both the performance and relaxation conditions. CONCLUSION: The
      findings of the present experiment demonstrate that modafinil can function as a
      reinforcer and that the reinforcing effects of modafinil are influenced by
      behavioral demands following drug administration, similar to those of other
      stimulant drugs.

PMID- 15986192
TI  - An evaluation of the sensitivity of the standardised field sobriety tests to
      detect the presence of amphetamine.
AB  - RATIONALE: The Standardised Field Sobriety Tests (SFSTs), designed and validated
      to assess impairment associated with alcohol intoxication, are currently being
      employed by the Victoria Police (Australia) for the identification of driving
      impairment associated with drugs other than alcohol. OBJECTIVES: The aim of this
      study was to evaluate whether the SFSTs are a sensitive measure for identifying
      the presence of dexamphetamine and methamphetamine. METHODS: Three studies each
      employed a repeated-measures, counterbalanced, double-blind placebo-controlled
      design. In each study, 20 healthy volunteers completed two treatment conditions:
      either 0.42 mg/kg d,l-dexamphetamine and placebo, 0.42 mg/kg d,l-methamphetamine
      and placebo, or 0.42 mg/kg d-methamphetamine and placebo. Performance was
      assessed using the SFSTs, consisting of the Horizontal Gaze Nystagmus test, the
      Walk and Turn test, and the One Leg Stand test. Blood and saliva samples were
      obtained before and immediately after the administration of the SFSTs (120 and
      170 min post drug administration). RESULTS: At 120 and 170 min post drug
      administration, d,l-dexamphetamine blood levels were 83.16 and 98.42 ng/ml,
      respectively; d,l-methamphetamine levels were 90 and 95 ng/ml, respectively; and
      d-methamphetamine blood levels were 72 and 67 ng/ml, respectively. None of the
      three amphetamine doses impaired performance on the SFSTs. Using the SFSTs, the
      presence of dexamphetamine was identified in 5% of cases, d-methamphetamine in
      5%, and d,l-methamphetamine in 0% of cases. CONCLUSIONS: Under these conditions,
      the SFSTs are not a sensitive measure for detecting the presence of low levels of
      amphetamine.

PMID- 15986193
TI  - Can an inert sleeping pill affect sleep? Effects on polysomnographic, behavioral
      and subjective measures.
AB  - RATIONALE: Since two recent meta-analyses on sleep changes associated with
      placebo in clinical trials suggested a beneficial effect of placebo treatments,
      pointing to a dissociation between subjective and objective measures of sleep,
      the current experiment was directly aimed to assess the effects of an inert
      compound, administered with the suggestion that it was a hypnotic substance in
      subjects with mild sleep complaints. OBJECTIVES: The aim of this study was to
      compare subjective, behavioral, polysomnographic (PSG), and quantitative
      electroencephalographic (EEG) changes during a night preceded or not by the
      intake of two 50-mg lactose capsules. METHODS: Ten female students, selected by
      the Pittsburgh Sleep Quality Index, slept for three consecutive nights in a sleep
      laboratory, with the experimental (EXP) night defined by the administration of
      two 50-mg lactose pills. Self-ratings of sleep quality and performance were
      assessed upon morning awakening of baseline (BSL) and EXP nights. RESULTS: The
      EXP nights were self-rated as more restful and characterized by a decreased
      number of nocturnal awakenings than the BSL nights. PSG measures showed that
      wakefulness after sleep onset significantly decreased during the EXP night as
      compared to the BSL night. The EXP nights also showed an increase of 0.5-4.0 Hz
      power during nonrapid eye movement sleep and a decrease of EEG activity in the
      beta frequency range during rapid eye movement sleep only at central brain sites.
      A specific improvement of behavioral measures was also found upon morning
      awakening after the EXP night compared to the BSL night. CONCLUSIONS: The
      administration of an inert pill improves both the subjective and objective
      quality of sleep. The reduced sleep fragmentation and the effects on some
      quantitative EEG markers of sleep homeostasis suggest that the experimental
      manipulation induced coherent changes in the subsequent sleep, resembling an
      enhancement of sleep pressure. The regional differences of EEG activity suggest
      the involvement of a specific physiological mechanism distinct from that of
      effective treatments.

PMID- 15986194
TI  - Enhanced 5-HT2C receptor signaling is associated with haloperidol-induced "early
      onset" vacuous chewing in rats: implications for antipsychotic drug therapy.
AB  - RATIONALE: Haloperidol is a representative of typical antipsychotics that are
      still in clinical use and which can lead to abnormal motor activity following
      repeated administration. The mechanisms underlying antipsychotic-induced
      dyskinesias are not well understood but are widely held to be related to
      excessive loss of dopamine function. In several models of dopamine hypofunction,
      serotonin 5-HT2C receptors have been shown to mediate vacuous chewing movements
      (VCM), a form of abnormal motor activity. It is well established that repeated
      haloperidol administration also elicits VCM, but there is no information on how
      repeated haloperidol administration affects 5-HT2C receptor signaling.
      OBJECTIVES: In the present study, we tested the hypothesis that repeated daily
      administration of haloperidol leads to enhanced serotonin 5-HT2C receptor
      signaling that is associated with increased 5-HT2C-mediated VCM. METHODS: Rats
      were treated by subcutaneous injection once daily for 21 days with either
      vehicle, a low dose of haloperidol (0.1 mg kg(-1) day(-1)), or a high dose of
      haloperidol (1.0 mg kg(-1) day(-1)). Following 1-day withdrawal, rats were either
      used for behavioral scoring of VCM or sacrificed for biochemical assessment of 5
      HT2 receptor-mediated phospholipase C activity and radioligand binding. VCM were
      scored following two successive "drug" challenges. The first challenge was an
      injection of vehicle (0.9% saline), and the second challenge was an injection of
      the 5-HT2C agonist meta-chlorophenylpiperazine (1.0 mg/kg). In this manner, a
      measure of "spontaneous" and "5-HT2C-elicited" orofacial activity could be made
      while minimizing animal use. RESULTS: Following 21-day haloperidol treatment at
      either dose, there was an increase in expression of meta-chlorophenylpiperazine
      induced VCM. In a separate experiment, meta-chlorophenylpiperazine-induced VCM
      were shown to be mediated through 5-HT2C receptors. Striatal 5-HT2C receptor
      mediated phospholipase C (PLC) activity and high-affinity agonist-labeled 5-HT2C
      receptors were also increased following either dose of haloperidol as compared to
      vehicle treatment. GTP-stimulated PLC activity and striatal Gq proteins were
      unchanged by haloperidol suggesting that enhanced signaling could be accounted
      for by alterations at the level of the receptor and not at downstream mechanisms.
      CONCLUSIONS: Repeated daily administration of haloperidol leads to an adaptive
      increase in 5-HT2C signaling which may contribute to abnormal motor function
      associated with antipsychotic use.

PMID- 15986195
TI  - Gender effect on the right-left discrimination task in a sample of heroin
      dependent patients.
AB  - RATIONALE: Discriminating right from left is an everyday cognitive ability.
      Repeated exposure to certain drugs, such as heroin, can produce poor performance
      on many cognitive tasks. However, it is yet unclear whether drug abuse impairs
      the ability of right-left discrimination. OBJECTIVES: The aim of the present
      study is to examine whether the spatial ability measured by the right-left
      discrimination task can be affected by heroin abuse and whether such drug effect,
      if it exists, is gender related. METHODS: A paper-and-pen test was used. The test
      consists of line drawings of a person with no arm, one arm, or both arms crossing
      the vertical body axis of the figure. The line drawings are viewed from the back,
      from the front, or randomly alternating between the back and front drawings. The
      subjects' task is to mark which is the right or left hand in the figure as fast
      as possible. RESULTS: A main finding in this study was that the ability to
      discriminate between left and right in visual space was impaired in heroin
      dependent patients. Especially, heroin-dependent females performed poorer than
      control females in all conditions but heroin-dependent males only performed
      poorly in part of conditions. CONCLUSIONS: Recent heroin abuse impairs the
      ability of right-left discrimination and such impairment is gender related:
      heroin-dependent females demonstrated greater performance deficits than males.

PMID- 15986196
TI  - Effect of repeated administrations of heroin, naltrexone, methadone, and alcohol
      on morphine glucuronidation in the rat.
AB  - RATIONALE: Heroin is rapidly metabolized to morphine that in turn is transformed
      in morphine-3-glucuronide (M3G), an inactive metabolite, and morphine-6
      glucuronide (M6G), a potent mu-opioid receptor (MOR) agonist. We have found that
      heroin addicts exhibit higher M6G/M3G ratios relative to morphine-treated control
      subjects. We have also shown that heroin-treated rats exhibit measurable levels
      of M6G (which is usually undetectable in this species) and reduced levels of M3G.
      OBJECTIVE: We investigated the role of MOR in these effects of heroin, by
      examining the effects of methadone, a MOR agonist, and of naltrexone, a MOR
      antagonist, on morphine glucuronidation. We also investigated the effects of
      alcohol, which is known to alter drug metabolism and is frequently coabused by
      heroin addicts. METHODS: Morphine glucuronidation was studied in liver microsomes
      obtained from rats exposed daily for 10 days to saline, heroin (10 mg/kg, i.p.),
      naltrexone (20-40 mg/kg, i.p.), heroin + naltrexone (10 mg/kg+20-40 mg/kg, i.p.),
      methadone (5-20 mg/kg, i.p.), or 10% ethanol. RESULTS: Heroin induced the
      synthesis of M6G and decreased the synthesis of M3G. Naltrexone exhibited
      intrinsic modulatory activity on morphine glucuronidation, increasing the
      synthesis of M3G via a low-affinity/high-capacity reaction characterized by
      positive cooperativity. The rate of M3G synthesis in the heroin + naltrexone
      groups was not different from that of the naltrexone groups. Methadone and
      ethanol induced a modest increase in M3G synthesis and had no effect on M6G
      synthesis. CONCLUSION: The effects of heroin on morphine glucuronidation are not
      shared by methadone or alcohol (two drugs that figure prominently in the natural
      history of heroin addiction) and do not appear to depend on the activation of
      MOR.

PMID- 15986197
TI  - Cannabinoid CB1 receptors are involved in motivational effects of nicotine in
      rats.
AB  - RATIONALE: The endocannabinoid system plays a role in mediating the appetitive
      value of a variety of reinforcing compounds, either natural rewards or drugs of
      abuse, but little is known about its involvement in the incentive properties of
      nicotine. OBJECTIVES: The objective of the study is to evaluate whether
      activation of CB1 cannabinoid receptors is necessary for the establishment and
      the short- and long-term expression of nicotine-induced conditioned place
      preference (CPP). This was studied in rats subjected to an unbiased, one
      compartment place conditioning procedure, using the selective CB1 receptor
      antagonist, rimonabant, as a pharmacological tool. METHODS: Wistar rats, given
      previous experience with nicotine in their home cage, were subjected to eight
      alternating nicotine (0.006-0.6 mg/kg s.c.) and saline pairings with distinct
      floor textures in an open field and given a test session, with no nicotine
      injection, in the open field whose floor was covered by two quadrants of the
      saline-paired texture and two quadrants of the nicotine-paired texture.
      Rimonabant (0.3-3 mg/kg i.p.) was administered 30 min before each nicotine (0.06
      mg/kg) pairing to assess its effect on the establishment of nicotine-CPP. To
      study the effects of CB1 receptor blockade on short- and long-term expression of
      nicotine-CPP, rimonabant was administered as a single injection 30 min before the
      test session, conducted either 24 h, 3 weeks or 12 weeks after the last
      conditioning session. RESULTS: Rats developed reliable and robust CPP to the 0.06
      and 0.125-mg/kg doses of nicotine. Once established, CPP persisted for at least
      12 weeks without additional exposure to nicotine and the test apparatus. Pre
      pairing injections of rimonabant (3 mg/kg, but not lower doses) prevented the
      acquisition of nicotine-CPP, and a single pretest administration of rimonabant (3
      mg/kg) abolished the expression of nicotine-CPP when the test session took place
      24 h after the last conditioning session. However, rimonabant (3 mg/kg) did not
      antagonize the expression of nicotine-CPP when the test session was conducted 3
      or 12 weeks after the acquisition phase. CONCLUSIONS: The endocannabinoids are a
      necessary component in both the perception by rats of the motivational value of
      nicotine and the short-term capacity of nicotine-paired conditioned stimuli to
      elicit approach behaviour. In contrast, the acute blockade of CB1 receptors no
      longer impairs the long-term control of behaviour by nicotine-associated
      environmental cues. These data provide support to the notion that the blockade of
      CB1 receptors can oppose tobacco dependence, withdrawal and even relapse, though
      the time window of efficacy and/or the schedule of administration remain to be
      established.

PMID- 15986199
TI  - Frequency and clinical expression of HFE gene mutations in a Spanish population
      of subjects with abnormal iron metabolism.
AB  - Three HFE gene mutations (HFE 845 G-->A, 187 C-->G and 193 A-->T) are the most
      common mutations related to hereditary haemochromatosis (HH). The genotype for
      these mutations was analysed in 359 Spanish individuals with altered iron
      metabolism and iron overload. Various biochemical parameters were measured in
      serum samples from 96 of these individuals, and the effect of the genotype on
      these parameters was studied. Allele frequencies were 12.95% for the HFE C282Y
      variant, 28.97% for the HFE H63D variant and 0.69% for the HFE S65C variant,
      calculated in a total of 718 chromosomes. Multiple comparisons analysis showed
      very significant differences (p=0.001) in transferrin saturation index (TSI)
      between the HFE C282Y variant homozygous and control (ten healthy volunteers)
      groups. Highly significant (p=0.0001) and significant (p=0.005) differences in
      serum ferritin values were found between the HFE C282Y variant homozygous and
      control groups and between compound (HFE C282Y/H63D variant) heterozygous and
      control groups, respectively. Very significant differences (p=0.001) in serum
      iron values were observed between the HFE C282Y variant homozygous and control
      groups. TSI and serum ferritin values detected most HFE C282Y variant homozygotes
      and are recommended to facilitate the clinical diagnosis of HH.

PMID- 15986198
TI  - Clozapine increases cutaneous blood flow and reduces sympathetic cutaneous
      vasomotor alerting responses (SCVARs) in rats: comparison with effects of
      haloperidol.
AB  - RATIONALE: Clozapine inhibits sympathetic outflow to the cutaneous vascular bed.
      Clozapine reverses hyperthermia and cutaneous vasoconstriction induced by 3,4
      methylenedioxymethamphetamine (MDMA, Ecstasy) or by lipopolysaccharide (LPS).
      Clozapine also reverses cutaneous vasoconstriction elicited by exposure to cold.
      These actions distinguish clozapine from haloperidol. Clozapine could also
      inhibit sympathetic cutaneous vasomotor alerting responses (SCVARs),
      vasoconstrictor episodes that reflect emotional/psychological function, and this
      property might also distinguish clozapine from haloperidol. OBJECTIVES:
      Experiments in rats determined whether clozapine and haloperidol inhibit SCVARs,
      and whether SR46349B (a 5HT2A receptor antagonist), 8-OH-DPAT (a 5-HT1A agonist),
      L741,626 (a dopamine D2 antagonist) or SCH23390 (a dopamine D1 antagonist) have
      clozapine-like effects on SCVARs. METHODS: Mean level and pulse amplitude of the
      tail artery Doppler flow signal were recorded in conscious freely moving rats
      before and after alerting stimuli (e.g. tapping the cage), and expressed as a
      SCVAR index (fall to zero flow implies SCVAR index of 100%, no fall implies 0%).
      RESULTS: Clozapine (0.0625-1.0 mg/kg, s.c.) dose-dependently increased resting
      tail blood flow. After 1 mg/kg, the SCVAR index was 18+/-1%, compared with 83+/
      2% after vehicle. SR46349B (0.01-1.0 mg/kg) and 8-OH-DPAT (0.25 mg/kg) had
      similar but less potent effects on cutaneous blood flow and on SCVARs.
      Haloperidol (0.005-0.5 mg/kg) and L741,626 (1 mg/kg) had no or little effect on
      these variables. SCH23390 mildly inhibited SCVARs. CONCLUSIONS: Clozapine, but
      not haloperidol, increases resting cutaneous blood flow and decreases SCVARs.
      Antagonism at 5-HT2A receptors and agonism at 5-HT1A receptors could contribute
      to these actions.

PMID- 15986200
TI  - Polymorphisms of interleukin-1 gene complex, IL6 and tumour necrosis factor genes
      in chronic idiopathic neutropenia of adults.
AB  - Chronic idiopathic neutropenia of adults (CINA) is a granulocytic disorder
      characterised by the "unexplained" decrease in the number of circulating
      neutrophils. Serum inflammatory cytokines and chemokines are increased in CINA.
      In addition, cytokines gene polymorphisms are associated with increased levels of
      respective products and related with inflammatory diseases. The aim of the
      present study was to investigate the association of polymorphisms of IL1B-511C/T
      and +3953C/T, IL1RN intron 2, IL6-174G/C and TNF-308G/A genes with CINA. We
      analysed 29 CINA and controls by polymerase chain reaction and restriction
      fragment length polymorphism. Statistical analyses were performed using chi2
      test, and the Hardy-Weinberg equilibrium (HWE) was investigated. All alleles
      analysed were in HWE in both populations. Similar frequencies of IL1B-511C/T,
      IL1B+3953C/T, IL1RN, IL6-174G/C and TNF-308G/A genotypes were observed in CINA
      and controls. These results suggest that cytokine polymorphisms associated with
      control of gene expression and protein levels were not associated with occurrence
      of CINA and were not responsible for the increased cytokine in CINA patients.

PMID- 15986201
TI  - The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes.
AB  - Brevenal is a nontoxic short-chain trans-syn polyether that competes with
      brevetoxin (PbTx) for the active site on voltage-sensitive sodium channels. The
      PbTxs are highly potent polyether toxins produced during blooms of several
      species of marine dinoflagellates, most notably Karenia brevis. Blooms of K.
      brevis have been associated with massive fish kills, marine mammal poisoning, and
      are potentially responsible for adverse human health effects such as respiratory
      irritation and airway constriction in beach-goers. Additionally, the consumption
      of shellfish contaminated with PbTxs results in neurotoxic shellfish poisoning
      (NSP). The purpose of the present study was to determine whether PbTx could
      induce DNA damage in a human cell type, the lymphocyte, and if so, whether the
      damage could be antagonized or ameliorated by brevenal, a brevetoxin antagonist.
      The DNA damage may occur through both endogenous and exogenous physiological and
      pathophysiological processes. Unrepaired or erroneously repaired DNA damage may
      result in gene mutation, chromosome aberration, and modulation of gene
      regulation, which have been associated with immunotoxicity and carcinogenesis. A
      single-cell gel electrophoresis assay, or comet assay, was used to determine and
      compare DNA damage following various treatments. The data were expressed as tail
      moments, which is the percentage of DNA in the tail multiplied by the length
      between the center of the head and center of the tail (in arbitrary units). The
      negative control tail moment was 29.2 (SE=+/-0.9), whereas the positive control
      (hydrogen peroxide) was 72.1 (1.5) and solvent (ethanol) was 24.2 (2.1). The PbTx
      2 (from Sigma, St. Louis, MO, USA), 10(-8) M was 41.3 (3.6), PbTx-9 (Sigma), 10(
      8) M was 57.0 (5.3), PbTx-2 (from University of North Carolina at Wilmington,
      UNCW), 10(-8) M was 49.4 (9.9), and PbTx-3 (UNCW), 10(-8) M was 64.0 (6.4). 1.0
      microg/ml brevenal applied 1 h before the PbTxs protected the lymphocytes from
      DNA damage; PbTx-2 (Sigma), 31.3 (2.1); PbTx-9 (Sigma), 35.5 (2.9); PbTx-2
      (UNCW), 33.9 (1.4); PbTx-3 (UNCW), 34.9 (1.25). The tail moment for 1.0 mug/ml
      brevenal alone was 30.8 (2.6). The results indicate that extensive genotoxic
      damage is induced by PbTx-2 and 9 (Sigma), and PbTx-2 and 3 (UNCW) in normal
      human lymphocytes, which is fully antagonized by brevenal. This suggests that the
      immune systems of individuals exposed to PbTx during harmful algal bloom (HAB)
      events may be at risk.

PMID- 15986202
TI  - Expression of lung resistance-related protein, LRP, and multidrug resistance
      related protein, MRP1, in normal human lung cells in long-term cultures.
AB  - Transport processes form part of the body's defense mechanism, and they determine
      the intracellular levels of many endogenous and exogenous compounds. The
      multidrug resistance-related protein MRP1 and the lung resistance-related protein
      LRP are associated with drug resistance against chemotherapeutics; they protect
      cells against toxic compounds. There is much experimental evidence to suggest
      that both of these transporter proteins serve important physiological functions.
      The expression of LRP and MRP1 was studied in normal human bronchial epithelial
      cells (NHBEC) and peripheral lung cells (PLC) obtained from explant cultures from
      morphologically-normal human lung tissue taken from patients with lung cancer.
      LRP (mRNA and protein) was detected in the cells of the bronchi as well as the
      peripheral lung with low (a factor of 2.6) inter-individual variation in the
      first generation. No significant alterations were noted for LRP within three-to
      four generations in the same patient. LRP expression was not substantially
      different between cultures from different topographic regions of the human lung.
      MRP1 protein and MRP1 mRNA could also be detected in all of the NHBEC and PLC
      cultures studied, but with substantially higher (a factor of 7.7) intra
      individual variation in the first generation than for LRP. MRP expression was the
      same for bronchial cells and PLC when the material was obtained from both sites.
      The level of mRNA for MRP1 was, in general, less stable than that for LRP. In
      multigeneration explant cultures, the levels of LRP mRNA and protein and MRP1
      protein did not fluctuate greatly, but the level of MRP1 mRNA dropped to about
      25% of the reference value within four generations (after about 8-10 weeks of
      culture). In one case, NHBEC subpassages were followed over a period of 20 weeks.
      In this system MRP mRNA levels increased by more than threefold, while levels of
      MRP1 protein and LRP mRNA and protein were expressed at almost constant rates.

PMID- 15986203
TI  - Weakness in the mechanical properties of the femurs of growing female rats
      exposed to cadmium.
AB  - The study assessed the effect of cadmium (Cd) intoxication on the risk of
      deformities and fractures of the growing bones of female rats, in order to model
      human exposure to this metal. For this purpose, bone mineral density and
      mechanical properties of the proximal and distal ends and diaphysis of the femur
      were investigated in female Wistar rats exposed to 1, 5 and 50 mg Cd/l in
      drinking water for 3, 6, 9 and 12 months after the onset of weaning. Daily Cd
      doses received from drinking water during the treatment period were in the
      following ranges: 0.059-0.219, 0.236-1.005 and 2.247-9.649 mg/kg body weight at
      1, 5 and 50 mg Cd/l, respectively. Biomechanical properties of the femoral
      proximal and distal ends were evaluated in a compression test, and those of the
      femoral diaphysis in a cutting test, with loading perpendicular to the
      longitudinal axis of the bone in all tests. The mineralization and mechanical
      properties of the bone tissue at various locations on the femur were affected by
      exposure to Cd in a dose- and duration-dependent manner. Exposure to 1 mg Cd/l
      (corresponding to low human exposure) during skeletal development weakened the
      fracture strength of the femoral neck and the trabecular bone at the level of the
      distal end of the femur and affected the elastic properties of the cortical bone
      at the femoral diaphysis. At higher levels of Cd exposure, adverse effects were
      generally observed after a shorter exposure period than for 1 mg Cd/l, and were
      more advanced. The cadmium-induced weakening of the biomechanical properties of
      bone at particular sites on the femur correlated with the decreased bone
      mineralization. The results indicate that even a low exposure to Cd may affect
      the mineralization and biomechanical properties of growing bone, thus enhancing
      the risk of fracture.

PMID- 15986204
TI  - The accuracy of ultrasound in the diagnosis of clinically occult groin hernias in
      adults.
AB  - This prospective study examined the accuracy of ultrasound in diagnosing occult
      groin hernias in adults. The study included 52 consecutive patients reviewed in
      the surgical out-patient clinic with a history suggestive of groin hernia but
      with a normal or inconclusive clinical examination. Each patient underwent a
      preliminary ultrasound examination by an experienced consultant radiologist who
      was aware that the patient had a history suggestive of a hernia but was blinded
      to the side of the symptoms. The patient then proceeded to herniography, and some
      patients also had surgical exploration. The results of the ultrasound were
      assessed in relation to the herniography, and the patients who proceeded to
      surgical exploration had further correlation with surgery. Ultrasound had a
      sensitivity of 29% and specificity of 90% compared with the herniography.
      Correlation with surgical findings showed ultrasound to have a sensitivity of 33%
      and a specificity of 100%. The sensitivity of ultrasound in detecting clinically
      occult hernias in a non-acute presentation is poor, and patients with normal
      ultrasound should be considered for further investigation.

PMID- 15986205
TI  - Developmental regulation of Suz 12 localization.
AB  - Chromatin modifications are among the epigenetic alterations essential for
      genetic reprogramming during development. The Polycomb group (PcG) gene family
      mediates chromatin modifications that contribute to developmentally regulated
      transcriptional silencing. Trimethylation of histone H3 on lysine 27, mediated by
      a PcG protein complex consisting of Eed, Ezh2, and Suz12, is integral in
      differentiation, stem cell self-renewal, and tumorigenesis. Eed and Ezh2 are also
      implicated in the developmentally regulated silencing of the inactive X
      chromosome, as they are transiently enriched on the inactive X chromosome when X
      chromosome silencing is initiated. Here we analyze the dynamic localization of
      Suz12 during cellular differentiation and X-inactivation. Though Suz12 is a
      requisite member of the Eed/Ezh2 complexes, we found that Suz12 exhibits a
      notable difference from Ezh2 and Eed: while Ezh2 and Eed levels decrease during
      stem cell differentiation, Suz12 levels remain constant. Despite the differential
      regulation in abundance of Suz12 and Eed/Ezh2, Suz12 is also transiently enriched
      on the Xi during early stages of X-inactivation, and this accumulation is Xist
      RNA dependent. These results suggest that Suz12 may have a function that is not
      mediated by its association with Eed and Ezh2, and that this additional function
      is not involved in the regulation of X-inactivation.

PMID- 15986206
TI  - The JIL-1 kinase regulates the structure of Drosophila polytene chromosomes.
AB  - The JIL-1 kinase localizes to interband regions of Drosophila polytene
      chromosomes and phosphorylates histone H3 Ser10. Analysis of JIL-1 hypomorphic
      alleles demonstrated that reduced levels of JIL-1 protein lead to global changes
      in polytene chromatin structure. Here we have performed a detailed
      ultrastructural and cytological analysis of the defects in JIL-1 mutant
      chromosomes. We show that all autosomes and the female X chromosome are similarly
      affected, whereas the defects in the male X chromosome are qualitatively
      different. In polytene autosomes, loss of JIL-1 leads to misalignment of
      interband chromatin fibrils and to increased ectopic contacts between
      nonhomologous regions. Furthermore, there is an abnormal coiling of the
      chromosomes with an intermixing of euchromatic regions and the compacted
      chromatin characteristic of banded regions. In contrast, coiling of the male X
      polytene chromosome was not observed. Instead, the shortening of the male X
      chromosome appeared to be caused by increased dispersal of the chromatin into a
      diffuse network without any discernable banded regions. To account for the
      observed phenotypes we propose a model in which JIL-1 functions to establish or
      maintain the parallel alignment of interband chromosome fibrils as well as to
      repress the formation of contacts and intermingling of nonhomologous chromatid
      regions.

PMID- 15986208
TI  - Fluorescence spectroscopy for monitoring deterioration of extra virgin olive oil
      during heating.
AB  - The potential of fluorescence spectroscopy for characterizing the deterioration
      of extra virgin olive oil (EVOO) during heating was investigated. Two commercial
      EVOO were analysed by HPLC to determine changes in EVOO vitamin E and polyphenols
      as a result of heating at 170 degrees C for 3 h. This thermal oxidation of EVOO
      caused an exponential decrease in hydroxytyrosol and vitamin E (R(2)=0.90 and
      0.93, respectively) whereas the tyrosol content was relatively stable. At the
      same time, amounts of preformed hydroperoxides (ROOH), analysed by an indirect
      colorimetric method, decreased exponentially during the heating process
      (R(2)=0.94), as a result of their degradation into secondary peroxidation
      products. Fluorescence excitation spectra with emission at 330 and 450 nm were
      recorded to monitor polyphenols and vitamin E evolution and ROOH degradation,
      respectively. Partial least-squares calibration models were built to predict
      these indicators of EVOO quality from oil fluorescence spectra. A global approach
      was then proposed to monitor the heat charge from the overall fluorescence
      fingerprint. Different data pretreatment methods were tested. This study
      indicates that fluorescence spectroscopy is a promising, rapid, and cost
      effective approach for evaluating the quality of heat-treated EVOO, and is an
      alternative to time-consuming conventional analyses. In future work, calibration
      models will be developed using a wide range of EVOO samples.

PMID- 15986207
TI  - Optochemical sensor for determining ozone based on novel soluble indigo dyes
      immobilised in a highly permeable polymeric film.
AB  - An optochemical ozone sensor is described that has been manufactured by
      immobilisation of novel soluble indigo derivatives in permeable transparent
      polymeric films of polydimethylsiloxane-polycarbonate copolymer. From a number of
      investigated indigo derivatives, 4,4',7,7'-tetraalkoxyindigo 9 has been selected
      for optimal sensitivity and specificity of ozone detection. A linear calibration
      for ozone can be obtained in the range between 0.01 and 0.5 ppm. The limit of
      quantitation is 0.03 ppm, and the accuracy exceeds 8%. It takes about 134 s to
      measure the relatively low occupational exposure concentration of 0.1 ppm. A
      reduction of the sensor response time could be achieved through application of
      double-sided coated sensors instead of single-sided variants. The stability of
      the sensors and the effect of external parameters like relative humidity (RH),
      temperature and gas flow on the sensor response have been investigated. The
      sensor response is affected by varying the gas flow or temperature; however,
      humidity in the range between 0 and 90% RH does not affect sensor response. The
      indigo derivative 9 remained stable inside the polymeric film and no chemical
      reaction, crystallisation or leaching occurred during 10 months of observation.
      Proper choice of indicator dye and polymeric material and successful application
      of kinetic evaluation method for the exposure experiments determine the desired
      features of the sensor.

PMID- 15986209
TI  - Rapid screening of selective serotonin re-uptake inhibitors in urine samples
      using solid-phase microextraction gas chromatography-mass spectrometry.
AB  - In this paper a solid-phase microextraction-gas chromatography-mass spectrometry
      (SPME-GC-MS) method is proposed for a rapid analysis of some frequently
      prescribed selective serotonin re-uptake inhibitors (SSRI)-venlafaxine,
      fluvoxamine, mirtazapine, fluoxetine, citalopram, and sertraline-in urine
      samples. The SPME-based method enables simultaneous determination of the target
      SSRI after simple in-situ derivatization of some of the target compounds.
      Calibration curves in water and in urine were validated and statistically
      compared. This revealed the absence of matrix effect and, in consequence, the
      possibility of quantifying SSRI in urine samples by external water calibration.
      Intra-day and inter-day precision was satisfactory for all the target compounds
      (relative standard deviation, RSD, <14%) and the detection limits achieved were
      <0.4 ng mL(-1) urine. The time required for the SPME step and for GC analysis (30
      min each) enables high throughput. The method was applied to real urine samples
      from different patients being treated with some of these pharmaceuticals. Some
      SSRI metabolites were also detected and tentatively identified.

PMID- 15986210
TI  - Amperometric determination of live Escherichia coli using antibody-coated
      paramagnetic beads.
AB  - Detecting and enumerating fecal coliforms, especially Escherichia coli, as
      indicators of fecal contamination, are essential for the quality control of
      supplied and recreational waters. We have developed a sensitive, inexpensive, and
      small-volume amperometric detection method for E. coli beta-galactosidase by bead
      based immunoassay. The technique uses biotin-labeled capture antibodies (Ab)
      immobilized on paramagnetic microbeads that have been functionalized with
      streptavidin (bead-Ab). The bead-Ab conjugate captures E. coli from solution. The
      captured E. coli is incubated in Luria Bertani (LB) broth medium with the added
      inducer isopropyl beta-D: -thiogalactopyranoside (IPTG). The induced beta
      galactosidase converts p-aminophenyl beta-D: -galactopyranoside (PAPG) into p
      aminophenol (PAP), which is measured by amperometry using a gold rotating disc
      electrode. A good linear correlation (R2 = 0.989) was obtained between log cfu
      mL(-1) E. coli and the time necessary to product a specific concentration of PAP.
      Amperometric detection enabled determination of 2x10(6) cfu mL(-1) E. coli within
      a 30 min incubation period, and the total analysis time was less than 1 h. It was
      also possible to determine as few as 20 cfu mL(-1) E. coli under optimized
      conditions within 6-7 h. This process may be easily adapted as an automated
      portable bioanalytical device for the rapid detection of live E. coli.

PMID- 15986212
TI  - Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17
      demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance.
AB  - PURPOSE: 17-DMAG is a hydrophilic derivative of the molecular chaperone inhibitor
      17-(allylamino)-17-demethoxygeldanamycin (17-AAG; NSC-330507), which is currently
      being evaluated for the treatment of cancer in clinical trials. 17-DMAG offers a
      potential advantage over 17-AAG because its aqueous solubility eliminates the
      need for complicated formulations that are currently used for administration of
      17-AAG. In addition, 17-DMAG undergoes only limited metabolism compared to 17
      AAG. The present results are from preclinical toxicity studies evaluating 17-DMAG
      in rats and dogs. METHODS: Doses of 0, 2.4, 12 and 24 mg/m2 per day were
      administered to rats, while dogs received doses of 0, 8 or 16 mg/m2 per day. In
      both species, 17-DMAG was administered i.v. (slow bolus for rats; 1-h infusion
      for dogs) daily for 5 days. An additional cohort of dogs received 16 mg/m2 per
      day orally for 5 days. Clinical observations were noted, and standard hematology
      and clinical chemistry parameters were monitored. Selected tissues were evaluated
      microscopically for drug-related lesions. Tissue and plasma 17-DMAG
      concentrations were measured by HPLC/MS at selected time-points on days 1 and 5.
      RESULTS: Daily i.v. administration of 17-DMAG at doses of 24 mg/m2 per day in
      rats or 16 mg/m2 per day in dogs produced lethality on day 6, approximately 24 h
      following the last dose. Body weight loss was common in rats and dogs. Drug
      related gastrointestinal, bone marrow and hepatic toxicities were also common in
      rats and dogs. Dogs also exhibited signs of renal and gallbladder toxicity.
      Plasma concentrations of 17-DMAG increased proportionately with dose in rats and
      disproportionately with dose in dogs. In rat tissues, however, only fourfold to
      sixfold increases in 17-DMAG concentrations were observed with a tenfold increase
      in dose. The highest concentrations of 17-DMAG were found in the liver of rats,
      with progressively lower concentrations in the spleen, lung, kidney and plasma.
      Regardless of the route of administration, higher drug concentrations were
      present in plasma (rat and dog) and tissue (rat) samples obtained on day 5
      compared to those obtained on day 1. Although plasma concentrations decreased
      with time, 17-DMAG was still detected in dog plasma for at least 24 h after drug
      administration. CONCLUSIONS: With the recent approval of 17-DMAG for clinical
      use, the data generated from these preclinical studies will provide guidance to
      clinicians as they administer this drug to their patients. The MTD of 17-DMAG was
      12 mg/m2 per day in rats and 8 mg/m2 per day in dogs; therefore, the recommended
      starting dose for phase I trial is 1.3 mg/m2 per day for 5 days. Gastrointestinal
      and bone marrow toxicity were dose-limiting in rats, and gastrointestinal, renal,
      gallbladder and bone marrow toxicity were dose-limiting in dogs. All adverse
      effects were fully reversible in surviving animals after treatment was complete.

PMID- 15986213
TI  - Simultaneous estimation of sludge biological activity and influent nitrogen load
      using ORP and DO dynamics.
AB  - This paper proposes a new optimization strategy to estimate nitrifiable nitrogen
      concentration in wastewater, nitrification rate, denitrification rate and/or COD
      available for denitrification of an activated sludge process submitted to
      intermittent aeration. The approach uses the oxydo-reduction potential and
      dissolved oxygen measurements only. The parameter identification is based on a
      Simplex optimization of a cost function related to the error between an
      experimental cycle (an aerobic period followed by an anoxic one) and a simulation
      of a reduced model derived from ASM1. Results show very good prediction of
      experimental oxygen, ammonium and nitrate profiles. The estimation of nitrifiable
      nitrogen and removal rates has been validated both on simulated data obtained
      from COST action 624 benchmark and on experimental data.

PMID- 15986214
TI  - A general model of reaction kinetics in biological systems.
AB  - Dynamic mathematical models in biotechnology require, besides the information
      about the stoichiometry of the biological reaction system, knowledge about the
      reaction kinetics. Modulation phenomena like limitation, inhibition and
      activation occur in different forms of competition with the key enzymes
      responsible for the respective metabolic reaction steps. The identification of a
      priori unknown reaction kinetics is often a critical task due to the non
      linearity and (over-) parameterization of the model equations introduced to
      account for all the possible modulation phenomena. The contribution of this paper
      is to propose a general formulation of reaction kinetics, as an extension of the
      Michaelis-Menten kinetics, which allows limitation/activation and inhibition
      effects to be described with a reduced number of parameters. The versatility of
      the new model structure is demonstrated with application examples.

PMID- 15986215
TI  - Unexpected behavior of coniferin in lignin biosynthesis of Ginkgo biloba L.
AB  - To gain insight into the behavior of monolignol glucoside in Ginkgo biloba L., we
      examined glucosides potentially involved in lignin biosynthetic pathway.
      Coniferin (coniferyl alcohol 4O-beta-D-glucoside) is a strong candidate for the
      storage form of monolignol. Coniferaldehyde glucoside may also have a role in
      lignin biosynthesis; this was examined with tracer experiments using labeled
      glucosides fed to stem segments. A series of tracer experiments showed that
      coniferin and coniferaldehyde glucoside were modified into coniferyl alcohol and
      then efficiently incorporated into lignin under the experimental conditions used.
      Interestingly, more than half of the administered coniferin underwent an
      oxidation to the aldehyde form before its aglycone; coniferyl alcohol was
      polymerized into lignin. This suggests that there is an alternative pathway for
      coniferin to enter the monolignol biosynthetic pathway, in addition to the direct
      pathway beginning with the deglucosylation of coniferin catalyzed by beta
      glucosidase. Enzymatic assays revealed that coniferaldehyde glucoside was
      produced enzymatically from coniferin, and that coniferaldehyde glucoside can be
      deglucosylated to yield coniferaldehyde, which could be fated to become coniferyl
      alcohol . Albeit the findings cannot be taken as proof for the in-planta
      functioning, these results present a possibility for the existence of alternative
      pathway in which some of the stored coniferin is oxidized to coniferaldehyde
      glucoside, which is deglucosylated to generate coniferaldehyde that joins the
      monolignol biosynthesis pathway.

PMID- 15986216
TI  - SKS6, a multicopper oxidase-like gene, participates in cotyledon vascular
      patterning during Arabidopsis thaliana development.
AB  - SKU5-Similar 6 (SKS6) is a one of a large gene family of 19 members in
      Arabidopsis thaliana (L.) Heynh that encode multicopper oxidase-like proteins
      that are related to ferroxidases, ascorbate oxidases and laccases. Only one
      member of the family has been previously studied; Skewed5 (SKU5) is involved in
      the control of root growth. The encoded SKS6 protein, like SKU5 appears to lack a
      functional copper-binding site and is most closely related to Bp10 from Brassica
      napus and Ntp303 from Nicotiana tobacum. The SKS6 promoter contains many putative
      regulatory sites and differential expression of an SKS6::GUS reporter gene
      revealed selective induction in several seedling tissues including guard cells,
      root cortex cells, and leaf margin hydathodes. It was also expressed later in
      flower development in flower primordia, ovules, and the abscission zones of seeds
      and siliques. Furthermore, SKS6 was upregulated in roots in response to treatment
      of seedlings with the hormones abscisic acid, indole-3 acetic acid, 2,4
      dichlorophenoxyacetic acid and aminocyclopropane-1-carboxylate. A loss-of
      function sks6-1 T-DNA insertion allele revealed that cotyledon vascular
      patterning is affected in the mutant, suggesting a role for the protein in
      metabolism of nutrients or hormones in the hydathodes, the sites of auxin
      synthesis and chemical recycling.

PMID- 15986217
TI  - Computational study on the difference between the Co-C bond dissociation energy
      in methylcobalamin and adenosylcobalamin.
AB  - The bond dissociation energies of the Co-C bonds in the cobalamin cofactors
      methylcobalamin and adenosylcobalamin were calculated using the hybrid quantum
      mechanics/molecular mechanics method IMOMM (integrated molecular orbital and
      molecular mechanics). Calculations were performed on models of differing
      complexities as well as on the full systems. We investigated the origin of the
      different experimental values for the Co-C bond dissociation energies in
      methylcobalamin and adenosylcobalamin, and have provided an explanation for the
      difficulties encountered when we attempt to reproduce this difference in quantum
      chemistry. Additional calculations have been performed using the Miertus-Scrocco
      Tomasi method in order to estimate the influence of solvent effects on the
      homolytic Co-C bond cleavage. Introduction of these solvation effects is shown to
      be necessary for the correct reproduction of experimental trends in bond
      dissociation energies in solution, which consequently have no direct correlation
      with dissociation processes in the enzyme.

PMID- 15986218
TI  - Pretreatment of diabetic rats with lipoic acid improves healing of subsequently
      induced abrasion wounds.
AB  - The etiology of delayed or impaired wound-healing in diabetic individuals is
      multifactoral, but peripheral vascular dysfunction is an underlying factor in the
      majority of cases. Recent studies have shown that lipoic acid improves vascular
      function in diabetic skin and reduces the symptoms associated with the diabetic
      peripheral neuropathy. In this study, rats were made diabetic with streptozotocin
      (STZ) and treated systemically on alternative days with lipoic acid (100 mg/kg
      given via intraperitoneal injection) for 8 weeks. Untreated STZ-diabetic rats and
      non-diabetic rats served as control. At the end of the 8-week period, rats from
      all the three groups were subjected to abrasion wound formation. Skin wounds
      healed more rapidly in untreated non-diabetic rats than in the untreated diabetic
      rats. Wounds in lipoic acid-treated diabetic rats healed more rapidly than wounds
      in untreated diabetic rats. Subsequent in vitro studies demonstrated that lipoic
      acid protected endothelial cells from oxidant injury. At the same time, lipoic
      acid had no apparent effect on endothelial cell proliferation and had no
      measurable effect on fibroblast function (proliferation, collagen synthesis and
      matrix metalloproteinase expression). These findings suggest that prophylactic
      use of lipoic acid might be useful in preventing the development of non-healing
      skin ulcers from minor traumas in at-risk skin.

PMID- 15986219
TI  - A priori implantation potential does not differ in eutopic endometrium of
      patients with and without endometriosis.
AB  - BACKGROUND: In endometriosis, angiogenesis is a crucial step for implantation of
      the exfoliates. A priori potential to induce angiogenesis by vascular endothelial
      growth factor (VEGF) expression was compared in eutopic endometrium of patients
      with and without endometriosis to discriminate the pivotal pathogenic step that
      differs in endometriosis. METHODS: In an experimental prospective study,
      endometrium samples were obtained from endometriosis patients (n=10) and from
      healthy, ovulating women as controls (n=6) undergoing curettage and laparoscopy
      for benign gynaecological conditions at the Aachen University Hospital, Aachen,
      Germany. Endometrial fragments were transplanted to the chicken chorioallantoic
      membrane (CAM) and re-explanted after 0, 24, 48, 72 and 96 h of cultivation for
      analysis. The main outcome measure was VEGF mRNA expression and protein
      localisation in endometrial fragments as parameters of angiogenic induction that
      was quantified by the vessel index. RESULTS: VEGF mRNA expression increased
      significantly in endometrial fragments of endometriosis and control patients
      (p<0.05). Protein is expressed in the glands and endometrial stroma. The vessel
      index is significantly elevated compared with native CAM controls. Endometrial
      fragments of endometriosis and control patients showed no significant differences
      in VEGF expression or angiogenic induction. CONCLUSIONS: Eutopic endometrial
      fragments of patients with and without endometriosis do not differ in their VEGF
      expression or angiogenic activity in the CAM assay. Implantation is obviously
      decided by external regulating influences on the exfoliates.

PMID- 15986220
TI  - Enhancement of a pentacyclic tyrosine kinase inhibitor production in Cladosporium
      cf. cladosporioides by Cladosporol.
AB  - The binaphthyl derivative cladosporol 3 was supplied from 60 to 200 mg l(-1) to
      shaken cultures of Cladosporium cf. cladosporioides. Compared to blank, fungal
      biomass was not affected by adding cladosporol till 100 mg l(-1): it rather
      increased at higher ratios between 150 and 200 mg l(-1). The production of the
      major pentacyclic metabolite 1, a cytokine production and tyrosine kinase
      inhibitor, was enhanced tenfold when cladosporol was supplied at the highest
      ratio (200 mg l(-1)) to shaken growing cultures of the fungus. The bioconversion
      of cladosporol to cladosporol D through reductive cleavage of the epoxide group
      was also observed. Interest in this kind of metabolites lies in their potential
      activity vs DNA topoisomerase I.

PMID- 15986221
TI  - [Childhood acne. Clinical expression, etiology, and relationship to juvenile
      acne].
AB  - Childhood acne has different clinical expressions which may be present from birth
      or manifest within the first weeks of life or after the third to sixth month of
      life. The condition may occur as a physiological phenomenon or may be
      pathological and require endocrinologic evaluation and treatment. It may be
      induced by drugs or ointments or due to intoxication. Severe courses with a
      tendency to scarring in childhood may be observed. Childhood acne may persist and
      develop into juvenile acne. It is likely that childhood acne may represent a risk
      factor for the development of severe acne in puberty.

PMID- 15986222
TI  - [Community-based MRSA. A new challenge for dermatology].
AB  - Treatment options for infections with MRSA are extremely limited because of
      resistance to all beta-lactam antibiotics and primarily because of the fast
      acquisition of further antibiotic resistance. During the past six years MRSA
      possessing the genomic determinant of an additional virulence factor emerged.
      This virulence factor, Panton-Valentine-Leukocidin, seems to be responsible for
      deep skin infections as well as necrotizing pneumonia. In order to avoid a
      continuous spread of MRSA, consequent prevention measures both in dermatological
      practices and for colonized patients in their general environment are essential.

PMID- 15986223
TI  - Cyclosporin A treatment upregulates Id1 and Smad3 expression and delays skeletal
      muscle regeneration.
AB  - The molecular signaling pathway linked to muscle regeneration has not yet been
      identified. Previously, we demonstrated that mice treated with cyclosporin A
      (CsA), a calcineurin inhibitor, failed to regenerate normally after muscle
      damage. Using reverse transcription (RT)-PCR, Western blot and
      immunohistochemical analysis, we investigated whether the amounts of nuclear
      factor of activated T cells (NFAT), myocyte-enhancer factor 2 (MEF2), the MyoD
      family, Id-1, and Smad3 change in the regenerating muscle after CsA treatment.
      Adult male ICR mice were subjected to a bupivacaine injection into the tibialis
      anterior muscle, and were treated with either CsA (25 mg/kg) or vehicle once
      daily. They were killed at 1, 2, 4, 6, 9 and 14 days post injury. RT-PCR analysis
      did not show a significant difference in MEF2s, MyoD and myogenin mRNA levels in
      the regenerating muscle in either placebo- and CsA-administered mice. In
      contrast, a significant increase in MRF4 mRNA was seen in CsA-administered mice
      compared to the placebo-treated mice at 4 and 9 days post surgery. In CsA-treated
      mice, the level of Id1 mRNA was elevated at day 9 relative to the placebo-treated
      mice. After 6 days, the CsA-treated mice possessed more abundant proliferating
      cell nuclear antigen (PCNA) and cyclin D1 protein in many satellite cells and/or
      myoblast-like cells in the regenerating muscle. The amount of myostatin, TGF
      beta2 and Smad3 mRNA and proteins was increased more markedly in the mice treated
      with CsA. After 9 days, many satellite cells and/or myoblasts showed apparent co
      localization of both MyoD and Smad3 in CsA-, but not in placebo-, treated mice.
      Our results demonstrated that CsA treatment upregulates Id1 and Smad3 expression
      and delays skeletal muscle regeneration in vivo.

PMID- 15986224
TI  - The RAGE pathway in inflammatory myopathies and limb girdle muscular dystrophy.
AB  - Oxidative stress and nuclear factor-kappaB (NF-kappaB) activation are linked to
      the pathogenesis of many metabolic, degenerative, and chronic inflammatory
      diseases. Activation of the receptor for advanced glycation end products (RAGE)
      by its specific ligand N(epsilon)-carboxymethyllysine (CML) results in the
      activation of NF-kappaB and the production of proinflammatory cytokines. To
      determine whether engagement of RAGE contributes to the pathogenesis of
      inflammatory myopathies, we performed immunohistochemical studies on the presence
      of CML-modified proteins, RAGE and activated NF-kappaB in muscle biopsies of
      patients with polymyositis (PM, n=10), dermatomyositis (DM, n=10), limb girdle
      muscular dystrophy (LGMD, n=10) and in 10 controls with normal muscle biopsy
      results. In inflammatory myopathies CML, RAGE and NF-kappaB were detected in
      mononuclear cells and in regenerating muscle fibers. CML, NF-kappaB and, to a
      lesser extent, RAGE were also found in degenerating muscle fibers, but
      colocalization of CML, RAGE and NF-kappaB was only seen in infiltrating
      mononuclear cells and regenerating muscle fibers. Immunofluorescence double
      labeling demonstrated an expression of CML, RAGE and NF-kappaB in CD4-, CD8-,
      CD22- and CD68-positive mononuclear cells. Western blot analysis showed an
      increased immunoreactivity for CML-modified proteins in PM and DM. In LGMD, CML,
      RAGE and NF-kappaB were found in regenerating muscle fibers and less frequently
      in degenerating muscle fibers, and with lower staining intensities than in
      inflammatory myopathies. Our data suggests that the CML-RAGE-NF-kappaB pathway is
      an evident proinflammatory pathomechanism in mononuclear effector cells in PM and
      DM. RAGE-mediated NF-kappaB activation may be involved in muscle fiber
      regeneration in inflammatory myopathies and LGMD.

PMID- 15986226
TI  - Delayed or late-onset type II glycogenosis with globular inclusions.
AB  - Three unrelated patients, one girl, one boy, and an adult female, aged 14, 11 and
      41 years, respectively, at the time of biopsy, revealed lysosomal glycogen
      storage, autophagic vacuoles and peculiar globular inclusions of distinct
      ultrastructure, which were reducing but did not appear like true "reducing
      bodies" as described in the congenital myopathy "reducing body myopathy". All
      three patients had residual activity of acid alpha-glucosidase in their muscle
      biopsy samples. Leukocytes in the girl showed normal acid alpha-glucosidase
      activity, but in the boy activity was reduced. Molecular genetic analysis of the
      GAA gene revealed disease-causing mutations in each patient: H568L/R672W, IVS1
      13T>G/G615F, and IVS1-13T>G/IVS1-13T>G. Although only one patient with such
      globular inclusions has been reported up to now, the three patients described
      here indicate that in the late-onset type of GSD II such inclusions may not be
      rare.

PMID- 15986225
TI  - Caspase-cleaved tau accumulation in neurodegenerative diseases associated with
      tau and alpha-synuclein pathology.
AB  - Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy
      (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are
      diseases associated with the accumulation of tau or alpha-synuclein. In AD, beta
      amyloid (Abeta)-associated caspase activation and cleavage of tau at Asp421
      (DeltaTau) may be an early step in neurofibrillary tangle (NFT) formation. To
      examine whether DeltaTau accumulates in other diseases not characterized by
      extracellular Abeta accumulation, we examined PiD, PSP, and CBD cases in
      comparison to those without extensive tau accumulation including frontotemporal
      lobar degeneration without Pick bodies (FTLD) and control cases. Additionally, we
      studied DeltaTau accumulation in DLB cases associated with intracellular alpha
      synuclein. DeltaTau was observed in all disease cases except non-PiD FTLD and
      controls. These results demonstrate that the accumulation of DeltaTau may
      represent a common pathway associated with abnormal accumulation of intracellular
      tau or alpha-synuclein and may be relatively less dependent on the extracellular
      accumulation of Abeta in non-AD dementias.

PMID- 15986227
TI  - Beta-methyl-xyloside: positive effect on xylanase induction in Cellulomonas
      flavigena.
AB  - Synthesis of extracellular xylanase in Cellulomonas flavigena is induced in the
      presence of xylan and sugarcane bagasse as substrates. The essential factors for
      efficient production of xylanase are the appropriate medium composition and an
      inducing substrate. The increase in xylanase production levels in C. flavigena
      were tested with a number of carbon sources and different culture conditions.
      Xylose, arabinose, glycerol and glucose did not induce xylanase production in
      this microorganism. beta-Methyl-xyloside (beta-mx), a structural analog of
      xylobiose, also did not induce xylanase when used as the sole carbon source, but
      when xylan or sugar cane bagasse was supplemented with beta-mx, extracellular
      xylanase production increased by 25 or 46%, respectively. The response of C.
      flavigena to xylan plus beta-mx was accompanied by a significant accumulation of
      reducing sugar, an effect not observed with the combination sugarcane bagasse
      plus beta-mx as substrate. To our knowledge, this is the first report on the
      effect of beta-mx on the induction of xylanase in C. flavigena.

PMID- 15986228
TI  - Edema in the retropharyngeal space associated with head and neck tumors: CT
      imaging characteristics.
AB  - To determine computed tomographic (CT) imaging characteristics of retropharygeal
      edema, we reviewed CT images in 18 patients with head and neck tumors.
      Retropharyngeal edema spread craniocaudally between soft palate and upper half of
      thyroid cartilage in all patients. No edema fluid extended above soft palate and
      below thyroid cartilage. Horizontally, it spread symmetrically in ten and
      asymmetrically in eight patients. Predominance in asymmetrical retropharyngeal
      edema was found on the same side as that of unilateral predominance both in lymph
      nodes enlargement and jugular vein stenosis/occlusion. All patients had edema
      also in other cervical spaces. Edema of retropharyngeal and other spaces
      fluctuated synchronously. In 14 patients, as primary lesion and/or cervical lymph
      nodes regressed, retropharyngeal edema disappeared or decreased. Retropharyngeal
      edema had some imaging characteristics. With knowledge of that, we could avoid
      diagnostic confusion when evaluating head and neck CT images.

PMID- 15986229
TI  - [Influence of gender on the intubation conditions with rocuronium].
AB  - PURPOSE: There is increasing evidence for gender differences in the
      pharmacokinetics and pharmacodynamics of anaesthetic drugs and neuromuscular
      blocking agents, e.g. rocuronium (Roc). Females require 30% less Roc than males
      to achieve the same degree of neuromuscular block and onset times are shorter.
      However, whether this leads to an improvement of the intubation conditions in
      females is unclear. METHODS: After approval of the ethics committee 60 female and
      60 male patients were each randomised into 2 groups to receive 0.6 mg/kg body
      weight Roc or 1.0 mg/kg succinylcholine (Sux; control group). Induction:
      thiopentone (5 mg/kg), fentanyl (3 microg/kg) then Roc (Roc groups) or Sux (Sux
      groups) and tracheal intubation after 60 s. Time to intubation, glottic exposure
      and intubating conditions were assessed. RESULTS: Men were significantly larger
      and heavier (p<0.001) than women, but the body mass index was comparable (ns).
      Number of attempts, time to intubation, and Cormack grades were comparable (ns).
      However, the rate of clinically acceptable intubation conditions was
      significantly higher in the female compared to the male Roc group: 80% vs 47%,
      p<0.05. The incidence of clinically acceptable intubation conditions in the
      female Roc and Sux groups were similar (80%). CONCLUSION: The intubation
      conditions after Roc were significantly better in women than in men. The
      differences were Roc-related and did not occur in the control groups.

PMID- 15986230
TI  - [Renal trauma. Treatment strategies and indications for surgical exploration].
AB  - Most renal injuries are blunt, involve a young patient population, and are caused
      by motor vehicle accidents or sport injuries. Renal trauma is classified into
      five grades with the majority of injuries being minor. CT scan has become the
      standard investigation method and should be performed in blunt trauma with
      macroscopic hematuria. Open trauma requires a radiological work-up in all forms
      of hematuria and in cases of clinical suspicion due to the wound entrance.
      Treatment management of most injuries has become conservative. Absolute
      indications for surgical revision are persistent life-threatening bleeding, renal
      pedicle injuries as well as an expanding, pulsatile retroperitoneal hematoma.
      Indications become relative in the presence of large devitalized renal tissue
      with urinary extravasation and other abdominal injuries, particularly of the
      pancreas and the colon. Surgical revision is more often indicated in open trauma,
      but surgery should enable renal reconstruction in the majority of cases.

PMID- 15986231
TI  - [Lesser toe deformities. Definition, pathogenesis, and options for surgical
      correction].
AB  - Whereas in the past resection arthroplasty was - in analogy to hallux valgus
      surgery - the preferred therapy to correct lesser toe deformities, the point of
      view has undergone a change. Much interest is directed toward functional aspects
      that require reconstructive management. Whenever possible the integrity of joint
      play should be saved. Above all the metatarsophalangeal joint of the lesser toes
      is worth being preserved to prevent a severe disturbance of the biomechanics of
      the foot. Tendon transfers and subtle corrective osteotomies such as the Weil
      procedure allow restricting resection procedures to contraction deformities.

PMID- 15986232
TI  - Comparison of BacT/ALERT 3D, Lowenstein-Jensen medium and Middlebrook 7H10/7H11
      biplate for recovering mycobacteria from clinical specimens.

PMID- 15986233
TI  - Tetanus and intravenous drug use.

PMID- 15986234
TI  - Staphylococcus aureus positive for Panton-Valentine leukocidin genes but
      susceptible to methicillin in patients with furuncles.
AB  - A total of 75 Staphylococcus aureus isolates obtained from patients with either
      recurrent skin abscesses or furuncles (n=48) or chronic infections from other
      body sites (n=27) were screened for the presence of the lukS-PV and lukF-PV genes
      encoding Panton-Valentine leukocidin. Significantly more isolates (70.8% vs.
      7.4%, p<0.001) from patients suffering skin abscesses or furuncles were positive
      for lukS-PV and lukF-PV. These isolates belonged to the accessory gene regulator
      (agr) group Ia (9/48), group III (13/48), or group IV (19/48). In contrast with
      results of other investigations, none of the isolates positive for the Panton
      Valentine leukocidin genes in this study exhibited methicillin resistance.

PMID- 15986235
TI  - The changing epidemiology of diabetic microangiopathy in type 1 diabetes.
AB  - Diabetic microvascular complications in the kidney and the eye are a major burden
      for diabetic patients due to increased morbidity and mortality. Furthermore,
      diabetic nephropathy is the leading cause of end-stage renal disease and diabetic
      retinopathy is the leading cause of blindness in younger patients, representing a
      major public health concern. During the past two decades beneficial effects of,
      in particular, aggressive antihypertensive control and strict glycaemic control
      have been demonstrated in randomised controlled clinical trials. Technological
      improvements in diabetes care have made good metabolic control easier to achieve.
      Has this led to an improved prognosis? In observational studies from dedicated
      centres, a decrease from 47 to 13% has been reported in the incidence of
      proliferative diabetic retinopathy after 20-25 years of diabetes, and the
      incidence of overt diabetic nephropathy after 20 years has decreased from 28 to
      5.8%. Even functional and morphological remission of diabetic nephropathy has
      been reported. Despite this, recent population-based studies have failed to
      demonstrate a decrease in the incidence of blindness caused by diabetes, and the
      incidence of end-stage renal disease has progressively increased. This may, in
      part, be the result of a combination of increasing numbers of diabetic patients
      and a lag phase between improvement in management and a decline in end-stage
      complications. It is of concern, however, that the results from specialised
      centres may not apply to routine diabetes care. It is, therefore, mandatory that
      the beneficial effects of pharmacological and non-pharmacological interventions
      demonstrated in clinical trials and recommended by treatment guidelines are
      translated into clinical practice to ensure a widespread improvement in
      prognosis.

PMID- 15986236
TI  - Oral probiotic administration induces interleukin-10 production and prevents
      spontaneous autoimmune diabetes in the non-obese diabetic mouse.
AB  - AIMS/HYPOTHESIS: Recent observations suggest the involvement of the
      gastrointestinal tract in the pathogenesis of islet autoimmunity. Thus, the
      modulation of gut-associated lymphoid tissue may represent a means to affect the
      natural history of the disease. Oral administration of probiotic bacteria can
      modulate local and systemic immune responses; consequently, we investigated the
      effects of oral administration of the probiotic compound VSL#3 on the occurrence
      of diabetes in non-obese diabetic (NOD) mice. METHODS: VSL#3 was administered to
      female NOD mice three times a week starting from 4 weeks of age. A control group
      received PBS. Whole blood glucose was measured twice a week. IFN-gamma and IL-10
      production/expression was evaluated by ELISA in culture supernatants of
      mononuclear cells isolated from Peyer's patches and the spleen, and by real-time
      PCR in the pancreas. Insulitis was characterised by immunohistochemistry and
      histomorphometric studies. RESULTS: Early oral administration of VSL#3 prevented
      diabetes development in NOD mice. Protected mice showed reduced insulitis and a
      decreased rate of beta cell destruction. Prevention was associated with an
      increased production of IL-10 from Peyer's patches and the spleen and with
      increased IL-10 expression in the pancreas, where IL-10-positive islet
      infiltrating mononuclear cells were detected. The protective effect of VSL#3 was
      transferable to irradiated mice receiving diabetogenic cells and splenocytes from
      VSL#3-treated mice. CONCLUSIONS/INTERPRETATION: Orally administered VSL#3
      prevents autoimmune diabetes and induces immunomodulation by a reduction in
      insulitis severity. Our results provide a sound rationale for future clinical
      trials of the primary prevention of type 1 diabetes by oral VSL#3 administration.

PMID- 15986237
TI  - Influence of Pro12Ala peroxisome proliferator-activated receptor gamma2
      polymorphism on glucose response to exercise training in type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Exercise training improves glycaemic control in some but not all
      individuals and little research has been done regarding genetic impact on the
      exercise training response in type 2 diabetes. The purpose of this study was to
      investigate the influence of the Pro(12)Ala variant of the peroxisome
      proliferator-activated receptor (PPAR) gamma2 gene on changes in fasting plasma
      glucose in response to exercise training. METHODS: The study population comprised
      139 sedentary type 2 diabetic patients (age: 54.4+/-7.2; HbA(1)c: 7.7+/-0.9%) who
      completed 3 months of supervised exercise training. The primary outcome variable
      in our analysis was the post-intervention change in blood glucose. Other
      assessments included measures of body composition, insulin sensitivity indices
      and maximal oxygen uptake (VO(2max)). RESULTS: The frequency of the Ala allele
      was 8.3% and the genotypes were in Hardy-Weinberg equilibrium. At baseline,
      neither body composition variables (weight, BMI, waist circumference), glucose
      homeostasis variables (glucose, insulin, HbA(1)c, homeostasis model assessment
      method) nor VO(2max) were different between genotypes (wild-type: Pro(12)Pro
      n=117, Ala carriers: X(12)Ala n=22). The exercise-training intervention led to
      similar improvements in body composition and glucose homeostasis variables in
      both genotype groups (p<0.05). The change in fasting plasma glucose was
      significantly different between PPARgamma2 genotypes (-1.66 mmol/l vs -0.54
      mmol/l, Ala carriers and wild-type, respectively) (p=0.034 unadjusted and p=0.089
      including baseline glucose) and the significant association between genotype and
      glucose response remained after adjusting for statistically significant
      predictors (age, changes in insulin and BMI [p=0.015]) and including baseline
      glucose, insulin and BMI (p=0.031). CONCLUSIONS/INTERPRETATION: These data
      suggest that the Pro(12)Ala polymorphism may influence the glycaemic response to
      exercise in type 2 diabetes.

PMID- 15986238
TI  - Importance of mitochondrial superoxide dismutase expression in insulin-producing
      cells for the toxicity of reactive oxygen species and proinflammatory cytokines.
AB  - AIMS/HYPOTHESIS: Free radicals generated in mitochondria play a crucial role in
      the toxic effects of cytokines upon insulin-producing cells. This study therefore
      investigated the role of manganese superoxide dismutase (MnSOD) in cytokine
      mediated toxicity in insulin-producing cells. METHODS: MnSOD was either stably
      overexpressed (MnSODsense) or stably suppressed (MnSODantisense) in insulin
      producing RINm5F cells. Cell viability was quantified after incubation with
      different chemical reactive oxygen species (ROS) generators and with cytokines
      (IL-1beta alone or a mixture of IL-1beta, TNF-alpha and IFN-gamma). Additionally,
      cell proliferation and endogenous MnSOD protein expression were determined after
      exposure to cytokines. RESULTS: After incubation with hydrogen peroxide
      (H(2)O(2)) or hypoxanthine/xanthine oxidase no significant differences were
      observed in viability between control and MnSODsense or MnSODantisense clones.
      MnSOD overexpression reduced the viability of MnSODsense cells after exposure to
      the intracellular ROS generator menadione compared with control and
      MnSODantisense cells. MnSODsense cells also showed the highest susceptibility to
      cytokine toxicity with more than 75% loss of viability and a significant
      reduction of the proliferation rate after 72 h of incubation with a cytokine
      mixture. In comparison with control cells (67% viability loss), the reduction of
      viability in MnSODantisense cells was lower (50%), indicating a sensitising role
      of MnSOD in the progression of cytokine toxicity. The cell proliferation rate
      decreased in parallel to the reduction of cell viability. The MnSOD expression
      level after exposure to cytokines was also significantly lower in MnSODantisense
      cells than in control or MnSODsense cells. CONCLUSIONS/INTERPRETATION: The
      increase of the mitochondrial imbalance between the superoxide- and the H(2)O(2)
      inactivating enzyme activities corresponds with a greater susceptibility to
      cytokines. Thus optimal antioxidative strategies to protect insulin-producing
      cells against cytokine toxicity may comprise a combined overexpression of
      H(2)O(2)-inactivating enzymes or suppression of MnSOD activity.

PMID- 15986239
TI  - Protein kinase-zeta interacts with munc18c: role in GLUT4 trafficking.
AB  - AIMS/HYPOTHESIS: Insulin-stimulated glucose transport requires a signalling
      cascade through kinases protein kinase (PK) Czeta/lambda and PKB that leads to
      movement of GLUT4 vesicles to the plasma membrane. The aim of this study was to
      identify missing links between the upstream insulin-regulated kinases and the
      GLUT4 vesicle trafficking system. MATERIALS AND METHODS: A yeast two-hybrid
      screen was conducted, using as bait full-length mouse munc18c, a protein known to
      be part of the GLUT4 vesicle trafficking machinery. RESULTS: The yeast two-hybrid
      screen identified PKCzeta as a novel interactor with munc18c. Glutathione S
      transferase (GST) pull-downs with GST-tagged munc18c constructs confirmed the
      interaction, mapped a key region of munc18c that binds PKCzeta to residues 295
      338 and showed that the N-terminal region of PKCzeta was required for the
      interaction. Endogenous munc18c was shown to associate with endogenous PKCzeta in
      vivo in various cell types. Importantly, insulin stimulation increased the
      association by approximately three-fold. Moreover, disruption of PKCzeta binding
      to munc18c by deletion of residues 295-338 of munc18c or deletion of the N
      terminal region of PKCzeta markedly inhibited the ability of insulin to stimulate
      glucose uptake or GLUT4 translocation. CONCLUSIONS/INTERPRETATION: We have
      identified a physiological interaction between munc18c and PKCzeta that is
      insulin-regulated. This establishes a link between a kinase (PKCzeta) involved in
      the insulin signalling cascade and a known component of the GLUT4 vesicle
      trafficking pathway (munc18c). The results indicate that PKCzeta regulates
      munc18c and suggest a model whereby insulin triggers the docking of PKCzeta to
      munc18c, resulting in enhanced GLUT4 translocation to the plasma membrane.

PMID- 15986240
TI  - Mitochondrial regulation of insulin production in rat pancreatic islets.
AB  - AIMS/HYPOTHESIS: The study was designed to identify the key metabolic signals of
      glucose-stimulated proinsulin gene transcription and translation, focusing on the
      mechanism of succinate stimulation of insulin production. METHODS: Wistar rat
      islets were incubated in 3.3 mmol/l glucose with and without esters of different
      mitochondrial metabolites or with 16.7 mmol/l glucose. Proinsulin biosynthesis
      was analysed by tritiated leucine incorporation into newly synthesised
      proinsulin. Preproinsulin gene transcription was evaluated following transduction
      with adenoviral vectors expressing the luciferase reporter gene under the control
      of the rat I preproinsulin promoter. Steady-state preproinsulin mRNA was
      determined using relative quantitative PCR. The mitochondrial membrane potential
      was measured by microspectrofluorimetry using rhodamine-123. RESULTS: Succinic
      acid monomethyl ester, but not other mitochondrial metabolites, stimulated
      preproinsulin gene transcription and translation. Similarly to glucose, succinate
      increased specific preproinsulin gene transcription and biosynthesis. The
      inhibitor of succinate dehydrogenase (SDH), 3-nitropropionate, abolished glucose-
      and succinate-stimulated mitochondrial membrane hyperpolarisation and proinsulin
      biosynthesis, indicating that stimulation of proinsulin translation depends on
      SDH activity. Partial inhibition of SDH activity by exposure to fumaric acid
      monomethyl ester abolished the stimulation of preproinsulin gene transcription,
      but only partially inhibited the stimulation of proinsulin biosynthesis by
      glucose and succinate, suggesting that SDH activity is particularly important for
      the transcriptional response to glucose. CONCLUSIONS/INTERPRETATION: Succinate is
      a key metabolic mediator of glucose-stimulated preproinsulin gene transcription
      and translation. Moreover, succinate stimulation of insulin production depends on
      its metabolism via SDH. The differential effect of fumarate on preproinsulin gene
      transcription and translation suggests that these processes have different
      sensitivities to metabolic signals.

PMID- 15986242
TI  - Toxocara canis in experimentally infected silver and arctic foxes.
AB  - In two experiments, thirty-six farm foxes of two species were inoculated with
      various doses of infective Toxocara canis eggs or tissue larvae isolated from
      mice. In experiment I, six adult arctic foxes (Alopex lagopus; 11-month old) were
      each inoculated with 20,000 eggs and sacrificed 100, 220, or 300 days post
      infection (dpi), while ten silver fox cubs (Vulpes vulpes; 6-9-week old) were
      infected with varying doses of eggs (30-3000) and necropsied 120 dpi. In
      experiment II, two groups of five cubs and two groups of five adult silver foxes
      received both a primary inoculation and either one or two challenge inoculations:
      primary inoculation (day 0) with 400 embryonated eggs were administered to five
      cubs and five adults and another five cubs and five adults received 400 larvae.
      At 50 dpi, the first challenge inoculation (400 eggs) was inoculated in all
      animals. At 100 dpi, three animals from each group were necropsied. The remaining
      two animals in each group were received a second challenge inoculation of 400
      tissue larvae on 100 dpi and were subsequently necropsied at 150 dpi. In both
      experiments, the highest numbers of larvae per gram (lpg) of tissue was found in
      the kidneys (100-300 dpi). In adult foxes receiving a high dose (20,000 eggs),
      increasing larval burdens were found in the kidneys over the course of the
      experiment (up to 300 dpi). The larval migration from the lungs to other tissues
      appeared to be dose-dependent with the highest larval burdens found in adult
      foxes. The faecal egg excretion, larval burden and intestinal worm burdens
      decreased from the first to the second challenge infection.

PMID- 15986243
TI  - Comparative study on the accumulation of heavy metals in different organs of
      tench (Tinca tinca L. 1758) and plerocercoids of its endoparasite Ligula
      intestinalis.
AB  - Concentrations of heavy metals (Cu, Fe, Zn, Mn, Cr, Pb and Cd) in some organs of
      tench and tissues of its parasite found in Kovada Lake (Turkey) were analyzed
      using atomic absorption spectrophotometry and subsequently compared with the data
      from sediments and water. Only Cu, Fe, Zn and Mn were detected in water,
      sediment, plerocercoids of Ligula intestinalis and fish samples, while levels of
      Cr, Pb and Cd were below the detection limits. Four elements were found at higher
      concentrations in the plerocercoid than in different fish tissues (muscle, liver
      and gill), being 1.6-37.4 times higher than that measured in muscle, liver and
      gill. Significant positive (for Cu) and negative (for Fe, Zn and Mn) correlations
      were found between the quantity of heavy metals in water and tissues of L.
      intestinalis plerocercoids while there were significant positive (for Cu and Zn)
      and negative (for Fe and Mn) correlations between the quantity of heavy metals in
      bottom sediment and tissues of L. intestinalis plerocercoids. Cestodes were found
      suitable to reflect the amount heavy metals in sediments, providing more reliable
      information about the actual pollution of the reservoirs.

PMID- 15986244
TI  - Selection of a precocious line of the rabbit coccidium Eimeria flavescens Marotel
      and Guilhon (1941) and characterisation of its endogenous cycle.
AB  - The SPF rabbits were inoculated with oocysts of Eimeria flavescens and the first
      newly developed oocysts were recovered. They were used for inoculation of other
      rabbits which consequently excreted oocysts sooner than in the previous passage.
      By repeated use of this method, the prepatent period was shortened after 18
      passages by more than 60 h. The endogenous development of this precocious line
      (PL) differed from that of the original strain (OS). Compared to OS, two asexual
      generations, second (or third) and fourth, were absent in PL. The first merogony
      took place in the jejunum and ileum in OS and, in contrast, in the large
      intestine in PL. Like in other rabbit coccidia, two types of meronts (A and B)
      were seen in each generation. However, the ratio of B: A meronts in the last
      (fifth) asexual generation as well as ratio of microgamonts:macrogamonts differs
      in OS and PL.

PMID- 15986245
TI  - Magnetic resonance imaging in experimental Chagas disease: a brief review of the
      utility of the method for monitoring right ventricular chamber dilatation.
AB  - Chagas' disease caused by infection with Trypanosoma cruzi leads to a
      myocardiopathy that evolves from the acute to the chronic phase. Magnetic
      resonance imaging (MRI) is an important tool for monitoring cardiac morphology
      and function both in humans and in animals. In the present work, we present a
      brief review of MRI applications for the study of ventricular hypertrophy and
      dilatation of the right ventricle in murine models of Chagas' disease. Studies
      using MRI demonstrate an increase in right ventricular chamber dimension during
      both phases of infection, indicating that increase of the right ventricle is a
      marker for experimental chagasic myocardiopathy. Based on previous studies using
      MRI in these models we propose that this technique is an excellent approach for
      monitoring heart functionality from the acute through the chronic phase of
      infection in different parasite-host pairs and for monitoring the efficacy of
      cardioprotective or immune-therapeutic agents.

PMID- 15986246
TI  - Appendiceal taeniasis presenting like acute appendicitis.
AB  - A case of parasitic appendicitis caused by Taenia sp. in a 28-year-old woman from
      Brazil is reported. Histopathological data and a description of the helminthe
      found in the appendix lumen are presented.

PMID- 15986247
TI  - Life cycle strategy of Hysterothylacium aduncum to become the most abundant
      anisakid fish nematode in the North Sea.
AB  - The present study demonstrates the influence of physical systems (mixed and
      stratified waters) on the occurrence and distribution of the anisakid nematode
      Hysterothylacium aduncum in commercially important gadiform fish species from the
      central and northern North Sea. Stratified waters are essential in structuring
      marine food webs and are therefore also important for the transfer of fish
      parasites to their host species. During two research cruises in 2001, 308
      haddocks (Melanogrammus aeglefinus) and 203 whitings (Merlangius merlangus) were
      caught in the central and northern North Sea and were examined for anisakid
      nematode parasites and food composition. Additionally, the most abundant pelagic
      invertebrates, hyperiid amphipods, of the investigated area were sampled and
      examined with regard to their parasite infestation rates. The influence of
      stratified waters on the infestation of the gadiform fish species by H. aduncum
      was shown by ecological and parasitological investigations. In stratified areas
      haddocks and whitings feed specifically and invariably on pelagic hyperiids. The
      number of ingested hyperiids in these areas was in both fish species correlated
      with infestation rates of H. aduncum. Therefore, hyperiids were identified as the
      obligatory intermediated host of H. aduncum, since these crustaceans carried high
      numbers of nematode larvae in their haemocoel. The results of the present study
      demonstrate that haddocks and whitings from the stratified waters are highly
      parasitised, both in terms of the numbers of individuals of larval and adult
      stages of H. aduncum.

PMID- 15986248
TI  - In vivo and in vitro analysis of chloroquine resistance in Plasmodium falciparum
      isolates from Senegal.
AB  - To determine the predictive value of chloroquine (CQ) resistance markers in
      Senegal, Plasmodium falciparum DNA polymorphisms in pfmdr1and pfcrt were examined
      in relation to clinical outcome. Despite CQ treatment, 17% of patients had
      parasitemia after 28 days. Examination of molecular markers of CQ resistance
      revealed that 64% of all isolates had the T76 resistant allele at the pfcrt
      locus, while 30% carried the Y86 resistant allele at the pfmdr1 locus. The pfcrt
      T76 allele was present not only in all in vivo resistant isolates, 89% of in
      vitro resistant isolates, but also in 35% of in vitro sensitive isolates. The
      pfmdr1 N86Y polymorphism did not correlate with in vitro or in vivo CQ
      resistance. Our data suggest that the pfcrt T76 allele alone is required but not
      a sufficient predictor for in vivo CQ resistance.

PMID- 15986249
TI  - Vaccination of buffaloes with Fasciola gigantica recombinant fatty acid binding
      protein.
AB  - Recombinant fatty acid binding protein (rFABP) of Fasciola gigantica was
      expressed in Escherichia coli and used as vaccine in Freund's adjuvant to
      evaluate the level of protection induced in buffalo (Bubalus bubalis) calves.
      Fifteen buffalo calves were distributed to three groups of five calves each. An
      antigen dose of 400 mug for each of the three immunizations at 3-week intervals,
      and a challenge dose of 600 metacercariae was administered per calf. Levels of
      anti-FABP antibodies increased rapidly by 2 weeks after the first immunization
      and were always significantly higher in the immunized-challenged group than in
      the infected control group. Immunization with FABP induced both humoral and cell
      mediated immune response in these animals. Vaccination showed a moderate level of
      protection in terms of reduced fluke burden (35.8%) and liver damage as assayed
      by aspartate aminotransferase and sulfhydryl group levels as well as anti
      fecundity effect of the vaccine.

PMID- 15986250
TI  - The ITS2 ribosomal DNA of Anopheles beklemishevi and further remarks on the
      phylogenetic relationships within the Anopheles maculipennis group of species
      (Diptera: Culicidae).
AB  - Anopheles beklemishevi specimens from Russia were analysed by their ITS2
      ribosomal DNA sequence to amend and to specify the phylogenetic tree of the
      Anopheles maculipennis species complex. Surprisingly, with 638 base pairs, the
      ITS2 regions of all the 34 An beklemishevi specimens examined were considerably
      longer than those of all their sibling species. Sequence alignment with GenBank
      derived sequences of the other siblings was only possible in the beginning (for
      approx. 335 bp) and at the end (for approx. 150 bp) of the PCR-amplified DNA
      fragment, whereas in the middle, the An beklemishevi DNA sequence found no
      counterpart in sequences of the other siblings. Closer analysis of this
      intermediate part suggests a duplicated insertion of about 140 bp that has
      undergone subsequent mutational changes. Due to this large putative insertion,
      computerized phylogenetic analysis by the Bayesian inference method locates An
      beklemishevi in a closer relationship to the nearctic than to the palaearctic
      sibling species. However, when only ITS2 regions are compared, that have
      corresponding sequences in the other siblings, An beklemishevi forms a lineage
      with the palaearctic species although it is still most remotely related. It is
      hypothesized that during the evolution An beklemishevi separated first from the
      common ancestor of the palaearctic species, which had presumably made its way
      from the Nearctic to the Palaearctic.

PMID- 15986251
TI  - Integration of Anopheles beklemishevi (Diptera: Culicidae) in a PCR assay
      diagnostic for palaearctic Anopheles maculipennis sibling species.
AB  - A few years ago a PCR-based assay for a quick and reliable identification of six
      palaearctic sibling species of the Anopheles maculipennis complex was presented
      making use of differences in the nucleotide sequence of the ITS2 ribosomal
      mosquito DNA. An. beklemishevi, which is distributed in Scandinavia and Russia
      only, has now been integrated into this test after analysis of its ITS2 region
      which turned out to be much longer than those of the other sibling species. Three
      oligonucleotides putatively specific for An. beklemishevi were constructed and
      tested in combination with a universal genus-specific primer for the
      amplification of an An. beklemishevi-specific ITS2 DNA-fragment. Two of the three
      oligos generated accurate and specific PCR products, even when used in a
      multiplex PCR together with the specific primers for the other six sibling
      species. Cross-hybridization of the primers to heterologous culicid DNA was never
      observed. The amplicons that identify An. beklemishevi consist of 554 and 735 bp,
      respectively, and are easily distinguished from those specific for the other
      sibling species after gel electrophoresis.

PMID- 15986252
TI  - Prevalence of theileriosis in Red Hartebeest (Alcelaphus buselaphus caama) in
      Namibia.
AB  - A total of 23 blood samples from Red Hartebeest and 28 ticks of the subspecies
      Rhipicephalus evertsi were collected in Namibia during the summer 2003. For a
      Piroplasmida species, Theileria sp 95.7% of blood and 50.0% of tick samples (all
      R. e. mimeticus, none of R. e. evertsi were carrying the pathogen) were PCR
      positive. Sequencing showed infection from a re-emerging mild species of
      Theileria phylogenetically different from other African Theileria species such as
      Theileria parva, T. buffeli, T. annulata, T. taurotragi or T. mutans.

PMID- 15986253
TI  - Occurrence and molecular characterization of Cryptosporidium spp. in mammals and
      reptiles at the Lisbon Zoo.
AB  - The presence of Cryptosporidium parasites in mammals and reptiles kept at the
      Lisbon Zoo was investigated. A total of 274 stool samples were collected from 100
      mammals and 29 reptiles. The species and genotype of the isolates identified by
      light microscopy were determined by nested PCR and sequence analysis of a
      fragment of the small subunit rRNA gene. Cryptosporidium oocysts were found in
      one black wildebeest (Connochaetes gnou), one Prairie bison (Bison bison bison)
      and in one Indian star tortoise (Geochelone elegans). The PCR and sequence
      analysis of these three isolates showed that those excreted by the Prairie bison
      were Cryptosporidium mouse genotype, those from the black wildebeest were from a
      new Cryptosporidium genotype and those infecting the Indian star tortoise were
      Cryptosporidium tortoise genotype. The present work reports a new Cryptosporidium
      genotype in a black wildebeest and the first finding of the Cryptosporidium mouse
      genotype in a ruminant.

PMID- 15986254
TI  - Is Leishmania (Viannia) braziliensis preferentially restricted to the cutaneous
      lesions of naturally infected dogs?
AB  - Nineteen dogs naturally infected with Leishmania (Viannia) braziliensis were
      studied in order to determine the presence of the parasite outside cutaneous
      lesions. Eleven (57.9%) animals showed single cutaneous or mucosal lesions and
      eight (42.1%) presented two or three lesions. Twenty-eight active lesions were
      biopsied. Isolation in culture and characterization by enzyme electrophoresis
      were possible in 100% of cases and amastigote forms were visualized upon
      histopathological examination in three samples (n=25, 12%). Isolation of the
      parasite in culture from peripheral blood and intact skin fragments obtained from
      the scapular region was negative in all animals, as was the histopathological
      analysis of skin from this region. Serological reactivity determined by an
      immunofluorescent antibody test and/or enzyme-linked immunosorbent assay was
      demonstrated in 15 animals. The results obtained suggest that L. braziliensis
      preferentially remains at the site of lesion, in contrast to the systemic
      distribution of parasites observed in dogs infected with L. (Leishmania) chagasi.
      A better understanding of this aspect may help direct diagnostic and control
      strategies applicable to areas characterized by the simultaneous occurrence of
      the cutaneous and visceral forms of leishmaniasis, as is the case for the
      Municipality of Rio de Janeiro, Brazil.

PMID- 15986255
TI  - Nematode parasites of the digestive tract in Neotropic cormorant chicks
      (Phalacrocorax brasilianus) from the River Cruces Ramsar site in southern Chile.
AB  - The neotropic cormorant (Phalacrocorax brasilianus) breeding colony of the Rio
      Cruces Nature Sanctuary and Ramsar site was surveyed for nematode parasites in
      southern Chile. Moribund chicks (n=128) of different ages were inspected for
      anchored nematodes using complete guts. We tested if chicks harbored the same
      parasites as the adults feeding them. Besides the known Contracaecum rudolphii,
      third or fourth stage larvae of Pseudoterranova sp. and Anisakis (type I and II)
      were obtained in this waterbird species for the first time. Most parasites were
      located in the stomach and C. rudolphii was the dominant species. The prevalence
      and mean intensity of C. rudolphii infections and the prevalence of Anisakis type
      I larvae were significantly less (P<0.05) in the youngest age group of the birds.
      The prevalence of Pseudoterranova sp. larvae infection was similar among birds of
      different age. The mean intensity with Pseudoterranova sp. was significantly less
      (P<0.05) in younger birds and in Anisakis type I it was similar in different age
      groups.

PMID- 15986256
TI  - Chloroplast and nuclear microsatellite analysis of Aegilops cylindrica.
AB  - Aegilops cylindrica Host (2n = 4x = 28, genome CCDD) is an allotetraploid formed
      by hybridization between the diploid species Ae. tauschii Coss. (2n = 2x = 14,
      genome DD) and Ae. markgrafii (Greuter) Hammer (2n = 2x = 14, genome CC).
      Previous research has shown that Ae. tauschii contributed its cytoplasm to Ae.
      cylindrica. However, our analysis with chloroplast microsatellite markers showed
      that 1 of the 36 Ae. cylindrica accessions studied, TK 116 (PI 486249), had a
      plastome derived from Ae. markgrafii rather than Ae. tauschii. Thus, Ae.
      markgrafii has also contributed its cytoplasm to Ae. cylindrica. Our analysis of
      chloroplast and nuclear microsatellite markers also suggests that D-type plastome
      and the D genome in Ae. cylindrica were closely related to, and were probably
      derived from, the tauschii gene pool of Ae. tauschii. A determination of the
      likely source of the C genome and the C-type plastome in Ae. cylindrica was not
      possible.

PMID- 15986257
TI  - [Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy].
AB  - A 32-year-old patient presented with presenile dementia syndrome and complex
      partial seizures. The dementia was preceded by recurrent bone pain which led to
      surgical intervention for ossear cysts. Computed tomography revealed
      intracerebral calcification and marked brain atrophy. Clinical, radiological,
      genetic, and histopathological features of PLOSL disease are discussed in the
      differential diagnosis of presenile dementia and basal ganglia calcification.

PMID- 15986258
TI  - [Suicidality in depressive children and adolescents during treatment with
      selective serotonin reuptake inhibitors. Review and meta-analysis of the
      available randomised, placebo controlled trials].
AB  - Due to concerns that selective serotonin reuptake inhibitors (SSRI) might be
      associated with an increased risk of suicidal ideation and suicide attempts in
      depressive children and adolescents, treatment with these drugs is controversial.
      All available data from randomised controlled trials on SSRIs treating depression
      in these age groups were examined regarding efficacy and suicidality. Results
      suggest that fluoxetine and, less clearly, sertraline are effective in such
      treatment. A meta-analysis yielded no statistically significant difference
      between treatment with SSRI and placebo with regard to the occurrence of suicidal
      behavior. Following evidence-based criteria, the risk:benefit ratio is favourable
      for fluoxetine and sertraline. Their use in the pharmacotherapy of depressive
      children and adolescents is indicated.

PMID- 15986259
TI  - [Reliability of multicenter magnetic resonance imaging. Results of a phantom test
      and in vivo measurements by the German Dementia Competence Network].
AB  - BACKGROUND: Whereas a large body of evidence suggests the usefulness of
      volumetric measurement of cerebral atrophy for diagnosing Alzheimer's disease
      (AD), the clinical applicability of cerebral volumetry for early detection of AD
      across multiple clinical sites is not well known. In the current study, we
      assessed the precision of volumetric measurement of the brain based on magnetic
      resonance imaging (MRI) in a multicenter setting. METHODS: The reliability of MRI
      was assessed by a phantom test of the American College of Radiology and voxel
      based morphometry applied to the images obtained from a single subject tested at
      11 centers of the German Dementia Competence Network. RESULT: Nine of the 11
      centers tested met the reliability criteria of the phantom test. Across all
      centers, a bias was found in the measurements of slice thickness and length. For
      voxel-based morphometry, the coefficient of variation yielded 5.02% for gray
      matter volume and 12.81% (SD 9.06%) for gray matter signal intensity in voxels.
      Power analysis showed that a sample size of 150 subjects is sufficient for
      statistically valid detection of reduced gray matter volume in patients with mild
      cognitive impairment. CONCLUSION: The reliability of measurements from multiple
      centers is sufficient to allow statistically valid analysis of MRI data.

PMID- 15986261
TI  - Pushing the boundaries for the use of ECMO in acute hypoxic respiratory failure.

PMID- 15986262
TI  - Laparoscopic resection rectopexy for rectal prolapse.
AB  - INTRODUCTION: The laparoscopic approach in suture rectopexy with sigmoid
      resection is appealing as surgery is mainly confined to the pelvis. METHODS: The
      procedure is performed in modified lithotomy position using five trocars. In the
      case reported, the inferior mesenteric artery is divided distally to the left
      colic artery branch. The sigmoid colon is mobilized medially and may be mobilized
      laterally up to the descending colon, depending on the extent of resection. The
      splenic flexure remains in place. The rectum is mobilized from the presacral
      fascia down to the pelvic floor, sparing the hypogastric nerves. The rectum is
      transected in its upper third and the colonic stump pulled outside after
      enlarging the left lower abdominal incision to a length of 5 cm. The colorectal
      anastomosis is established intracorporeally in a double-stapling technique. Three
      2-0 braided nonabsorbable sutures are placed to attach the right lateral stalks
      of the rectum to the presacral fascia. Proctoscopic examination has to ensure
      that there is no luminal compromise or air leakage. RESULTS: The videotape
      reports about a 37-year-old male patient with a rectal prolapse of 8 cm in
      length. First symptoms had occurred in childhood. He reported about temporary
      constipation and repeated rectal bleeding. During surgery, an elongated sigmoid
      was found. Laparoscopic sigmoid resection and suture rectopexy were carried out.
      There were no intraoperative or postoperative complications. The patient was
      discharged from the hospital on the sixth postoperative day. CONCLUSION:
      Laparoscopic resection rectopexy is safely feasible as a minimally-invasive
      treatment option for rectal prolapse.

PMID- 15986263
TI  - Performance of four clinical screening tools to select peri- and early
      postmenopausal women for dual X-ray absorptiometry.
AB  - Several methods to select postmenopausal women for dual X-ray absorptiometry
      (DXA) have been proposed. We decided to compare the performance of three clinical
      decision rules (SCORE, ORAI, OST) with the usual case-finding strategy based on
      the presence of a major risk factor for future fracture (CFMRF). The study
      subjects were 2009 healthy, white, peri- or early postmenopausal women
      participating in the Danish Osteoporosis Prevention Study (DOPS). DXA results
      expressed as T-scores and scores on SCORE, ORAI, OST and CFMRF were extracted
      from the DOPS database. First, we evaluated the screening tools as originally
      described by the developers. The resulting sensitivities and specificities ranged
      from 18% to 92% and from 66% to 85%, respectively. Only OST achieved a high
      sensitivity (92%) with respect to femoral neck T-score < or = -2.5; however, the
      sensitivity with respect to lumbar spine T-score < or = -2.5 was only 51%. Next,
      the performance of the screening tools was evaluated against T-score < or = -2.0
      (and T-score < or = -2.5) in at least one of the regions: femoral neck, total hip
      or lumbar spine. Using ROC curve analysis, we determined cut-offs yielding
      sensitivities as close as possible to 90%. The CFMRF and the ORAI tool were too
      coarse to yield 90% sensitivity. The performances of OST and SCORE were equal
      from a clinical perspective in that the sensitivities and the specificities
      varied from 89% to 94% and from 23% to 28%, respectively. The performance of
      CFMRF was no better than could be expected by chance, yielding a sensitivity of
      19% and a specificity of 85%. Applying SCORE or OST 75% of the women would have
      to be referred for densitometry to identify 90% of the women with T-score < or = 
      2.0 (or T-score < or = -2.5) in at least one region. In conclusion, our results
      question the utility of all the evaluated tools for screening peri- and early
      postmenopausal women for low BMD. However, if a decision on referral has to be
      made, it may be based on the simple OST rule, which performed as well as or
      better than any of the other tools.

PMID- 15986264
TI  - Ebstein's anomaly - review of a multifaceted congenital cardiac condition.
AB  - Ebstein's anomaly (EA) is a rare but fascinating congenital heart disorder
      accounting for <1% of all congenital heart defects. Since its description in
      1866, dramatic advances in diagnosis and therapy have been made. In this review,
      we describe current diagnostic criteria and classification, natural history,
      clinical features, and prognosis, typical echocardiographic features and
      pathologic findings, and the spectrum of associated cardiac malformations
      including left heart anomalies associated with EA. Differences between Ebstein
      like changes associated with congenitally corrected transposition and EA are
      described. The spectrum of typical ECG and conduction system changes, arrhythmias
      including accessory pathways and ectopic atrial tachycardias related to EA are
      also reviewed. Differential diagnosis of EA is discussed including tricuspid
      valve dysplasia and prolapse as well as arrhythmogenic right ventricular
      cardiomyopathy. The review describes management options in EA including catheter
      interventions, indication for operation and surgical options including tricuspid
      valve repair and replacement. Overall, EA is a complex congenital anomaly with a
      broad pathologic-anatomical and clinical spectrum and no two patients are alike.
      Therefore, precise knowledge of the different anatomic and hemodynamic variables,
      associated malformations and management options are essential. Management of EA
      patients is complex. Thus it is important that these patients are regularly seen
      by a cardiologist with expertise in congenital heart disease.

PMID- 15986265
TI  - Methadone-induced Torsade de pointes tachycardias.
AB  - Methadone is a synthetic opioid frequently used in drug maintenance programs for
      heroin addicts. It prolongs the QT-interval and is mainly metabolized by the
      isoenzyme CYP3A4 of the hepatic cytochrome-P450-system, which is used by numerous
      other QT-prolonging agents. Its most severe side effect is the development of
      life-threatening Torsade de pointes ventricular tachycardia in the setting of a
      prolonged QT-interval. Since drug addicts are prone to concomitant medical
      conditions requiring additional medication as well as to continued abuse of
      cocaine, they are at higher risk for developing this major complication of
      methadone therapy. Before subjecting patients on methadone to other drugs, the QT
      interval should be determined and it should be ascertained whether the new agent
      has the property to prolong the QT-interval or is metabolised by the cytochrome
      P450 system.

PMID- 15986266
TI  - Incidence of contrast nephropathy in patients receiving comprehensive intravenous
      and oral hydration.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) remains a major complication of
      percutaneous coronary interventions (PCI) and a common cause of acute renal
      failure. The most effective preventive strategy is unknown. OBJECTIVES: This
      study sought to estimate the incidence of CIN in patients receiving comprehensive
      intravenous and oral volume supplementation for PCI during which iopromide
      (Ultravist 370, Schering, Berlin, Germany) was used. METHODS: We prospectively
      studied the development of CIN in 425 consecutive patients undergoing PCI,
      applying comprehensive intravenous and oral hydration in all patients. Baseline
      renal function was assessed by calculating the glomerular filtration rate (GFR)
      with the use of the abbreviated Modification of Diet in Renal Disease Study
      equation. CIN was defined as an increase in serum creatinine of at least 0.5
      mg/dl (44 mmol/l) within 48 hours. RESULTS: Mean patients' age (mean +/- SD) was
      64 +/- 10 years. A total of 133/425 patients (31%) were 70 years or older, 107
      (25%) were women, 70 (16%) were diabetics, 218 (51%) had prior myocardial
      infarction, and 43 (10%) underwent PCI for an acute ST-segment elevation
      myocardial infarction. Mean GFR was 89 ml/min/1.73 m2. Glomerular filtration rate
      was below 60 ml/min/ 1.73 m2 in 43 patients (10%). During PCI 226 +/- 80 ml of
      iopromide were used. With the comprehensive hydration strategy used, CIN
      developed in only 6 of 425 (1.4%; 95% confidence interval 0.5-3.1%) patients. No
      patient required dialysis. CONCLUSIONS: Applying the combination of intravenous
      and oral volume supplementation results in a very low incidence of CIN following
      PCI. Hydration remains the cornerstone for the prevention of CIN.

PMID- 15986267
TI  - Anti-infectious prophylaxis after splenectomy: current practice in an eastern
      region of Switzerland.
AB  - Overwhelming post-splenectomy infection (OPSI) is a long-term risk in asplenic
      patients, which may be minimised by appropriate preventive measures. In this
      survey anti-infectious strategies after splenectomy were evaluated in an eastern
      part of Switzerland. We found 91 individuals in the canton of Thurgau, who
      underwent splenectomy between 1998 and 2003. We assessed adherence to vaccination
      guidelines, the use of antibiotics and the awareness of the infectious risks by
      review of hospital charts and by structured interviews with patients and their
      general practitioners. The total vaccination rate was 64/91 (70%). 6 patients
      were vaccinated pre-operatively, 50 during the hospital stay and 8 after
      discharge by the general practitioner. 64 received vaccination against
      pneumococci, 6 against haemophilus influenzae and 3 against meningococci.
      Although 39 died during the study period, none died of overwhelming sepsis. None
      of the patients received a booster vaccination. Prophylactic long-term
      antibiotics were given to 2 children but to none of the 89 adults. Three adults
      had a supply of stand-by antibiotics at home. Less than half of the patients who
      were interviewed knew that asplenia puts them at greater risk for life
      threatening infections and few practitioners were aware that travel and animal
      bites pose a special threat. We conclude that after splenectomy vaccination
      discipline and patient education should be substantially improved and suggest the
      publication of comprehensive guidelines.

PMID- 15986268
TI  - [Intracorneal rings: why?].

PMID- 15986269
TI  - Are women more likely to be blind or visually impaired than men?

PMID- 15986271
TI  - [Orbital xanthogranulomatosis].

PMID- 15986272
TI  - [Non-Langerhans' cell histiocytosis].

PMID- 15986273
TI  - [Orbital rhabdomyosarcoma: difficulties with European treatment protocol].
AB  - PURPOSE, MATERIAL AND METHODS: To present the experience in management of orbital
      rhabdomiosarcoma over 21 years in our centre. Review of the 12 cases of
      paediatric rhabdomiosarcoma and results of treatment in terms of mortality and
      morbidity comparing our results with other studies. RESULTS/CONCLUSION:
      Management of orbital rhabdomyosarcoma following the European Protocol leads to
      poor results compared with the American protocol. Early radiotherapy and complete
      tumoral excision could play a role in management of this tumour

PMID- 15986274
TI  - [Oral clarithromycin as a treatment option in chronic post-operative
      endophthalmitis].
AB  - PURPOSE: To assess the outcome of medical treatment with oral clarithromycin in
      patients with chronic post-surgical endophthalmitis. METHODS: This prospective
      study was performed between January 1999 and September 2003. Patients with a
      diagnosis of chronic post-surgical endophthalmitis of bacterial etiology were
      included. All received 500 mg of oral clarithromycin twice a day for 14 days. The
      initial and final visual acuity, etiology, post-surgical time of presentation,
      treatment-delay time, and follow up were recorded. According to the treatment
      results, patients were distributed into 3 separate groups: 1) complete response,
      2) partial response, 3) no response. Data from these groups were compared by
      means of the Student's t test and Fisher exact test, depending on which was
      considered most suitable. RESULTS: Fifteen cases of chronic endophthalmitis (11
      of Propionibacterium acnes, 4 of Staphylococcus epidermidis) were diagnosed. A
      complete response was observed in 4 cases, partial response in 4 cases, and no
      response in 7 cases. Final visual acuity greater than 0.5 was significantly more
      likely in the complete response group when compared with the no response group
      (Fisher exact test = 0.0454, p=0.05), however, the same comparison between the
      complete response group and the partial response group was not significant.
      CONCLUSION: Medical treatment with oral clarithromycin could be useful in some
      patients with chronic post-surgical endophthalmitis.

PMID- 15986275
TI  - [Comparative study of amniotic membrane transplantation, with and without
      simultaneous application of mitomycin C in conjunctival fornix reconstruction].
AB  - OBJECTIVE: To describe the results of amniotic membrane (AM) transplantation,
      using the simultaneous application of 0.02% Mitomycin C (MMC), in conjunctival
      fornix reconstruction. MATERIAL: We compared two groups of patients: group A, who
      were treated only with AM and group B, in whom MMC (0.02%) was also applied.
      Operative technique used: In group A, the surgical procedure involved a careful
      removal of the cicatricial tissue, followed by AM transplantation. In group B,
      following the careful removal of the cicatricial tissue, 0.02% MMC was then
      applied to the surgical field for 60 seconds, and this was followed by extensive
      irrigation with saline solution. AM transplantation was then performed. We
      ultimately evaluated the depth of the conjunctival fornix and ocular motility.
      RESULTS: Group A: eleven eyes of eleven patients were evaluated. Seven had
      chemical injuries, three had traumatic symblepharon and one had Stevens-Johnson
      syndrome. In two cases a 7 mm or greater conjunctival fornix depth was observed.
      In four cases the ocular motility was better than -1. Group B: Twelve eyes of
      twelve patients were evaluated. Seven had chemical injuries, 2 had traumatic
      symblepharon and 3 had Stevens-Johnson syndrome. In nine cases a 7 mm or greater
      conjunctival fornix depth was obtained. In 9 cases the ocular motility
      restriction was resolved. Poor results of fornix reconstruction, as well as
      ocular motility, were observed in those patients with autoimmune diseases,
      irrespective of the treatment used. CONCLUSIONS: The simultaneous combination of
      AM and MMC results in better conjunctival fornix reconstruction than with the use
      of AM alone.

PMID- 15986276
TI  - [Management of lymphoid hyperplasia of the ocular adnexa].
AB  - OBJECTIVE: Lymphoid Hyperplasia (LH) is a benign proliferative lymphocyte-rich
      process. Histologically, LH may be similar to a lymphoma. Its incidence has
      decreased because of new sophisticated diagnostic procedures and a better
      knowledge of lymphomas. Most of the cases are seen in patients between forty and
      sixty years of age. As there was no consensus about the best treatment,
      determining this was the objective of our study. METHOD: We describe three
      patients with a lymphoproliferative process affecting the ocular anexae, in whom
      histologic, immuno-histochemical and molecular studies were performed. PCR
      analysis allowed a definitive diagnosis to be made. RESULTS: Histologically, all
      three cases were diagnosed as LH; immuno-histochemically, one was diagnosed as an
      idiopathic orbital inflammation, and the other two, as LH. After PCR analysis,
      one of these latter two cases was definitively diagnosed as B-cell Non-Hodgkin's
      lymphoma. CONCLUSIONS: Today's molecular techniques allow us to make a definite
      diagnosis of lymphoma, because sometimes histology and immuno-histochemistry
      alone can result in a wrong diagnosis being made. LH of the ocular adnexae may be
      the first stage of a much more serious disease, and a benign hyperplasia at this
      site must lead to suspicion of lymphoma, which can then be diagnosed or excluded
      by the improved diagnostic procedures. Therefore, when we make a diagnosis of LH
      it is necessary to complete a full evaluation and institute a defined follow-up
      of the patient's clinical condition.

PMID- 15986277
TI  - [Surgical treatment of acquired myogenic eyelid ptosis].
AB  - OBJECTIVE: To report the surgical outcome of aponeurosis surgery in patients with
      acquired myogenic eyelid ptosis and describe surgical guidelines for their
      correction. METHODS: The clinical records of two patients with acquired myogenic
      eyelid ptosis after surgical correction were reviewed. RESULTS: In two patients
      with acquired myogenic eyelid ptosis and barely good levator function, levator
      resection surgery was performed. Corneal complications appeared in both cases.
      CONCLUSION: Patients with acquired myogenic eyelid ptosis are at risk of post
      operative surgical complications from corneal exposure. Surgical correction
      should be conservative and performed only when the visual axis is compromised.

PMID- 15986279
TI  - [The elementary treatment of eye diseases by Lorenzo Baro (1899). II].

PMID- 15986278
TI  - [Conjunctival blistering associated with pemphigus vulgaris: report of a case].
AB  - CLINICAL CASE: A patient with a conjunctival blister was diagnosed with pemphigus
      vulgaris by immunofluorescence tests performed on a conjunctival biopsy.
      DISCUSSION: Pemphigus vulgaris is an uncommon but serious autoimmune disease that
      produces blisters of the skin and mucous membranes. Ocular findings are rare, but
      include conjunctivitis and marginal eyelid erosions. Conjunctival blisters and
      erosions related to this condition have not been previously reported in the
      literature. This diagnosis can be made through direct immunofluorescence tests
      performed on biopsy samples of affected tissue. Unless the condition is properly
      diagnosed and treated, it has a high mortality.

PMID- 15986281
TI  - [Fighting for the best: the new procedure for the selection of medical students].

PMID- 15986282
TI  - [The German short version of "Profile of Mood States" (POMS): psychometric
      evaluation in a representative sample].
AB  - The German short version of "Profile of Mood States" (POMS) was psychometrically
      tested in a representative sample (1009 subjects in Eastern Germany and 1034
      subjects in Western Germany). The 35 items (7 point scale, instruction "How you
      have been feeling during the past 24 hours?") form the following scales:
      Depression/Anxiety, Fatigue, Vigor, Hostility. The POMS appears to be an
      internally consistent instrument (Cronbach's Alpha from 0.89 to 0.95).
      Replication of the postulated 4 factors was limited. There are hints for
      convergent validity of POMS-Scales using two questions: "1. Over the past two
      weeks, have you felt down, depressed, or helpless?" and "2. Over the past two
      weeks, have you felt little interest or pleasure in doing things?"

PMID- 15986283
TI  - [Weight concerns and dieting among 8 to 12-year-old children].
AB  - According to a recent study it could be shown that more than one third of female
      high school students and more than 20 % of male students in the age of 14 to 18
      years indicated an impaired eating behaviour, expressed as a medium or high risk
      to develop eating disorders based upon the standardized Eating Attitudes Test
      (EAT) . The current study tested the prevalence of weight concerns and dieting as
      an indicator of problematic eating behaviour among younger children. 230
      Thuringian female and male students in the 3 (rd) and 4 (th) year (between 8 and
      12-years-old) as well as their parents were investigated using standardized and
      modified instruments. Weight and height were measured directly to determine the
      Body Mass Index (BMI) that was put into relation to some factors of potential
      influence such as parents, peers, media and eating behaviours. It could be shown
      that 42 % of the boys and 53 % of the girls preferred a thin ideal body image; 32
      % of the children revealing normal weight expressed the wish to be thinner. 18 %
      of the boys and 19 % of the girls tried to lose weight at the time of the
      investigation. Dieting was influenced by the perceived (not actual) dieting
      behaviour of the parents. The BMI significantly predicted weight concerns: In
      total, 85 % of the overweight children but also 17 % of the children with normal
      weight were convinced to be overweight. The girls' eating behaviour was mostly
      influenced by the peers, the boys' behaviour by criticism of the parents.
      Generally, a significant influence of the media could be demonstrated.

PMID- 15986284
TI  - [Individual therapists in inpatient psychotherapy -- a pilot study on their
      importance for therapeutic outcome].
AB  - OBJECTIVE: How much does the individual psychotherapist influence therapy outcome
      in a multimodal inpatient setting with several therapeutic relationships and the
      additional influence of group processes. METHODS: We studied the outcome of n =
      293 psychotherapy inpatients (mean treatment duration: 11 weeks) who were treated
      in an integrated inpatient concept by 9 mostly psychodynamically oriented
      psychotherapists (professional experience 0.5 to 7 yrs, 13 to 56 patients per
      therapist). Patients had an extensive evaluation of process and outcome variables
      (e. g. SCL 90R, IIP, Global outcome rating, Helping Alliance Questionnaire -
      HAQ). Differences in outcome between patients of different therapists were
      calculated. RESULTS: Patients assigned to the participating therapists did not
      differ in their basic clinical characteristics, except in the clinical severity
      rating carried out by therapists themselves. Outcome in the SCL90R - GSI residual
      score and global rating differed significantly between the therapists (d (SCL
      pooled SD) = 0.43 to 1.10, explained variance: 10 %). The same holds true for the
      therapeutic alliance (HAQ, explained variance: 45 %). Assessment of therapeutic
      relationship shows good correlation between patients and therapists, outcome
      assessment does not. Therapists differed in the degree of matching between their
      own and their patients' evaluations. CONCLUSIONS: We found significant therapist
      differences in outcome and alliance. Despite the multifaceted inpatient setting
      the individual therapist is an important determinant of therapeutic success.

PMID- 15986285
TI  - [Alexithymia in a clinical sample].
AB  - OBJECTIVES: The Toronto Alexithymia Scale (TAS-20), is currently the most widely
      used measure of alexithymia. An alternative measure of alexithymic
      characteristics is the Levels of Emotional Awareness Scale (LEAS). Aim of the
      study was to investigate, wether LEAS and TAS-20 scores are associated with
      interpersonal problems, sociodemografic variables, and psychological strain in a
      construct conform direction. METHODS: 146 psychosomatically ill in-patients
      completed the TAS-20, the LEAS, the Symptom Check List (SCL-90-R) and the
      inventory for the assessment of interpersonal problems (IIP-D). RESULTS: Low
      emotional awareness (LEAS) was associated with male gender, absence of a stable
      partnership and low educational level. In contrast to LEAS, TAS-20 was
      significantly correlated with the majority of the SCL-90-R and IIP scales.
      CONCLUSIONS: The correlations between TAS-20 and IIP scales may be an indication
      for the validity of the measurement. The association between low emotional
      awareness and sociodemografic variables are costructconform and indicate a strong
      relationship between LEAS and variables, that represent real life.

PMID- 15986286
TI  - Management of reflux disease in clinical praxis in hungary.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a chronic condition that
      affects a large proportion of the population. The majority of patients are
      treated in the primary care but effective management of the disease still remains
      a challenge for specialists as well. A recent survey - based on the case of a
      typical GERD patient - conducted in Germany indicated that mainly specialists
      adhered to the guidelines. AIM: The purpose of this study was to conduct a survey
      among specialists and primary care physician members of the Hungarian Society of
      Gastroenterology about the practical management of GERD using the same
      questionnaire as in the German study. METHODS: A questionnaire based on the case
      of a typical patient with GERD was sent out to a total of 1090 members of the
      society. The questions concerned general measures for avoiding reflux symptoms
      (dietary and life-style modifications), diagnosis of GERD and the type of
      treatment. Answers were compared with those in the German study. RESULTS: A total
      of 421 questionnaires were evaluated (38 %), which had been returned by 174
      general practitioners (GP), 173 gastroenterologists (GE), 41 paediatricians, and
      33 surgeons. Only 9 % (38/421) of the responders think that there is no necessity
      to carry out specific diagnostic approaches before starting any treatment. In 91
      % of the cases (25 % always and 66 % only if symptoms persist) doctors carry out
      specific diagnostic tests (75 % endoscopy, 13 % 24 hours pH-metry, and 12 % X
      ray). 47 % of responders start drug treatment at once while 35 % start
      medications only after getting the results of the requested examinations. 18 % of
      Hungarian doctors do start with a non-medical therapy. Almost all responders feel
      that it is important to advise a reduction of weight and a cessation of smoking
      for GERD patients. Altering specific dietary and life-style habits was considered
      useful by more than 85 % of our responders. Hungarian physicians were more
      concerned about different alcoholic drinks and spicy, fatty or bloating meals and
      less about sweets than their German counterparts. More than 85 % of GPs
      administer some kind of drug therapy as first choice. Over 65 % of GPs are using
      the step-down approach with proton pump inhibitors as the initial strategy and 78
      %, 76 %, and 81 % of GEs, paediatricians, and surgeons, respectively, do the
      same. Almost one-third of GPs and paediatricians are willing to continue therapy
      and almost two-thirds of GPs will reduce the dose of current medical therapy if
      the GERD patient is responding well to the initial therapy. CONCLUSIONS:
      Irrespective of the country, specialists are adhering more strictly to the
      guidelines on the diagnosis and treatment of GERD than general practitioners. The
      majority of responders, however, ask for endoscopy prior to initiation of any
      medication and use the step-down approach. Despite the lack of scientific
      evidence, reduction of weight, cessation of smoking, dietary and life-style
      modifications are still part of the treatment of GERD in both Germany and
      Hungary.

PMID- 15986287
TI  - Peptic ulcer disease in dyspeptic patients with ischemic heart disease: search
      and treat?
AB  - OBJECTIVE: The aim of this study was to determine the prevalence and risk factors
      for peptic ulcer disease (PUD) in dyspeptic patients with ischemic heart disease
      (IHD), and to assess whether the healing of PUD before coronary artery bypass
      grafting (CABG) could reduce the need for urgent postoperative endoscopy.
      PATIENTS AND METHODS: A series of 894 patients referred to Dubrava University
      Hospital in Zagreb for elective CABG during the period from May 1998 until April
      2001 was prospectively analysed. Dyspepsia was assessed by a questionnaire, PUD
      by upper gastrointestinal endoscopy, and H. pylori status by histology/Giemsa
      staining and the rapid urease test. The need for urgent postoperative endoscopy
      (hematemesis and/or melena, sudden onset of anemia or unexplained epigastric
      pain) was compared between the prospective study group of 894 patients and a
      series of 463 patients referred for CABG to Dubrava University Hospital during
      the period from January 1997 until April 1998. RESULTS: Gastroduodenal dyspepsia
      predominated in 184 (20.6 %) patients, 142 (77.2 %) of them with Helicobacter
      (H.) pylori infection and 69 (37.5 %) with verified PUD. Univariate analysis
      indicated the increased risk of multiple PUD to be related to a previous
      diagnosis of PUD (OR 3.61, 95 % CI 1.32 - 9.82), H. pylori infection (OR 18.86,
      95 % CI 2.31 - 153.98), use of aspirin (OR 5.70; 95 % CI 1.80 - 18.03) and left
      coronary artery occlusions (3.10, 95 % CI 1.00 - 9.59). Multivariate analysis
      pointed to H. pylori infection (OR 16.30, 95 % CI 1.57 - 168.53) and left
      coronary artery occlusions (OR 4.84, 95 % CI 1.05 - 22.30) as independent risk
      factors for multiple PUD. The OR for urgent postoperative endoscopy due to a
      major gastrointestinal event was 9.9 (95 % CI 2.2 - 45.1) and the OR for active
      peptic ulcer with stigmata of recent bleeding was 6.9 (95 % CI 1.4 - 33.1) in the
      group of patients with IHD who were not submitted to evaluation for dyspepsia
      prior to elective heart surgery. CONCLUSIONS: In areas with a high prevalence of
      H. pylori infection, endoscopy and a "search and treat" strategy for IHD patients
      with dyspepsia before elective cardiac surgery should significantly reduce the
      need for urgent postoperative endoscopy due to major gastrointestinal events.

PMID- 15986288
TI  - Impact of dominant stenoses on the serum level of the tumor marker CA19-9 in
      patients with primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Patients with primary sclerosing cholangitis (PSC) have an
      increased risk of developing hepatobiliary tumors. The tumor marker CA19-9 was
      claimed to indicate the occurrence of bile duct carcinoma. This study aimed to
      assess whether increased serum levels of CA19-9 in PSC patients with dominant
      stenoses indicate bile duct carcinoma. METHODS: The study cohort comprised 106
      patients treated over a median time of 5.0 years (range 0.5 - 13 years). All
      patients were treated with ursodeoxycholic acid (UDCA) and whenever they
      developed dominant stenoses by endoscopic dilatation of these stenoses. In
      endoscopically treated patients, CA19-9 levels were measured before and 3, 6, 12
      and 24 months after endoscopic dilatation. RESULTS: Of the 106 patients, 22
      carcinoma-free patients and 3 patients with bile duct carcinoma had elevated CA
      19 - 9 levels. In 14 out of 25 patients with elevated CA19-9 levels, dominant
      stenoses were diagnosed and treated by endoscopic dilatation. In 71.4 % of the
      endoscopically treated patients, CA19-9 levels decreased following the endoscopic
      intervention. CONCLUSIONS: In PSC patients, increased serum levels of CA19-9 are
      rarely due to the development of bile duct carcinoma. In patients with dominant
      stenoses, the relief of biliary obstruction by endoscopic dilatation may lead to
      a decrease of the serum levels of CA19-9.

PMID- 15986289
TI  - [A case of attenuated familial adenomatous polyposis coli (AFAP)].
AB  - We describe an asymptomatic female patient who was diagnosed with multiple
      tubular and tubulovillous adenomas in the right-sided colon on routine
      colonoscopy at the age of 59 years. Genetic testing identified a germline
      truncating mutation at codon 405 (R405X) of the adenomatous polyposis coli (APC)
      gene. This mutation is located in the alternatively spliced region of exon 9, a
      region that is associated with an attenuated phenotype of familial adenomatous
      polyposis (AFAP). To our knowledge this report describes for the first time the
      R405X germline mutation in association with AFAP. Our patient had no extracolonic
      manifestations of AFAP. Treatment consisted of a right hemicolectomy with
      ileotransversal anastomosis plus complete endoscopic polypectomy in the left
      sided colon. AFAP is a poorly defined condition with unknown prevalence and
      penetrance that requires individual therapy and life-long surveillance. Because
      of marked intrafamilial phenotypic variance, it is crucial to identify these
      patients and implement proper endoscopic surveillance at an early age in family
      members carrying this mutation.

PMID- 15986290
TI  - Amelanotic malignant melanoma of the esophagus: case report.
AB  - We present the case of a primary malignant esophageal melanoma arising in a 75
      year-old male, initially diagnosed as anaplastic squamous cell carcinoma. After
      resection of the tumor, histological work-up was indicative of a marked
      morphological heterogeneity, resembling a focally amelanotic primary malignant
      melanoma. Primary malignant melanomas of the esophagus are exceptionally rare. An
      exact preoperative diagnosis is critical with respect to the appropriate
      therapeutic strategy. Clinicopathological features of this entity with a brief
      review of the literature are presented.

PMID- 15986291
TI  - [Probiotics--from empirical medicine to therapeutic standard].
AB  - Due to the lack of proven efficacy and an unidentified mode of action, probiotics
      were dismissed by the traditional medical sector for many years. In the meantime,
      the clinical efficacy of some probiotics has clearly been substantiated in GCP
      compliant studies. In addition, modes of action have been demonstrated which
      prove the effects of probiotics on a cellular level and replace the concept of
      "restoring the disturbed intestinal microbial balance". Different probiotics have
      distinct modes of action and the clinical efficacy of various probiotics has been
      proven in distinct indications. Today, some probiotics represent therapeutic
      standards in certain indications.

PMID- 15986295
TI  - [Evaluation of women-centered health care in Taiwan].
AB  - A great number of hospitals have already started to develop women-centered wards
      and out-patient services, but there has been no evaluation from the perspective
      of gender of the quality of these so-called women-centered health service models
      and whether they are truly based on women's needs. This article evaluates these
      service models from a feminist perspective. We performed content analysis of
      cases at those hospitals that took part in the Department of Health's women
      centered health care program in 2002. The results showed that the program's
      content was based on improvements in hardware and work flow, and, furthermore,
      enhanced patient privacy and the humanized nature of the patient environment.
      Some issues, like the interaction between doctor and patient, women's
      consultation needs, the right to make one's own decisions, and body awareness,
      were somewhat neglected. Some of the hospitals, however, had achieved break
      through reforms and outcomes in management of procedures, innovative services
      (e.g., women's health centers and databases of women's health management), growth
      groups and health consultation rooms. In many hospitals, levels of satisfaction
      among women were raised, but standards of retention and continued development of
      the effects of the program remain imperfect. Common problems were confusion of
      the concepts of mother-infant centered and women centered care, lack of
      consideration of gender mainstreaming, lack of needs assessment, and inadequacy
      of outcomes evaluation skills.

PMID- 15986292
TI  - [Primary sclerosing cholangitis is a premalignant condition].
AB  - Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown
      aetiology. The course of the disease is usually progressive with the development
      of liver cirrhosis leading to death or liver transplantation within an average of
      12 years. To date it is well known that the development of hepatobiliary
      malignancies and the rate of colonic mucosal dysplasia and carcinoma in patients
      with concomitant ulcerative colitis are greatly enhanced in patients with PSC.
      PSC can therefore be regarded as a premalignant condition. The following review
      will focus on the development of cholangiocellular carcinoma in patients with PSC
      and the associated diagnostic and therapeutic challenges.

PMID- 15986296
TI  - [Caring for teenage girls: from the perspective of establishing women's health
      consultations on campuses].
AB  - Women's health problems are increasing among teenage girls in modern society.
      However, there are only a few programs related to women's health consultation on
      campuses. Three issues are explored in this paper - the health rights of teenage
      girls, women's health consultations, and teenage girls' subjective views about
      the establishment of a women's health consultation service on their campus. In
      the course of our research of teenage girls' subjective views, three hundred and
      eighty-seven young girl students responded to questionnaires and seven volunteer
      students among them were invited to do in-depth interviews. Most students (98.2%)
      thought that it was necessary to set up a women's health consultation service on
      campus, because they hoped to get personal health information that could not be
      found in a textbook. Three hundred and five (78.8%) students perceived that they
      had women's health problems. Their health problems are ranked as follows:
      dysmenorrhea, irregularity of menstrual periods, unusual vaginal secretions and
      questions of contraception and urinary system health. They suggested that campus
      consultation centers should have the following characteristics: protection of
      students' privacy, provision of multiple channels for consultation, strict
      limitation on numbers of people in the consulting office, and a non
      discriminatory policy towards all clients. Hopefully, an information database can
      provide a good reference for establishing a women's health consultation service
      on campus in the near future.

PMID- 15986297
TI  - [Constructing a breastfeeding-friendly workplace: demonstration from hospital].
AB  - To breastfeed is a right of women and infants. However, breastfeeding is viewed
      as a " Private domain" rather than as a "public domain" issue. Many people
      therefore think that it is unnecessary to use public policy to solve problems
      associated with breastfeeding. Nurses, due to heavy work loads and
      responsibilities, and shift rotation, have to face many difficulties when they
      combine breastfeeding and work. Since the question of whether nurses may
      successfully breastfeed their offspring in the workplace is one of particular
      significance, this article considers the importance of breastfeeding in the
      workplace and nurses experiences thereof, and the international criteria for a
      friendly breastfeeding workplace for women, in order to discuss ways in which
      Taiwan's health care institutions should create breastfeeding-friendly
      environment.

PMID- 15986298
TI  - [Humanized childbirth].
AB  - Childbirth is a major event in a family. The expectant parent's perception of the
      childbirth experience influences his or her development as a parent. Making
      childbirth a positive and satisfying experience for women is the responsibility
      of health care providers. Women want to have physical and emotional privacy
      during labor and delivery, and to experience both in a friendly, comfortable
      environment. For women expected to undergo normal deliveries, humanized
      childbirth is one accessible approach. This article explores the definition and
      evolution of humanized childbirth and the care practice that it involves. It also
      explores birth plans and birth experiences, and the improvements necessary to
      routine labor practices to enable women to participate in decision making about
      their childbirth experiences. The author emphasizes that when health-care
      providers recognize the value of humanized childbirth and make changes
      accordingly, the dignity of women's childbirth experiences will be enhanced.

PMID- 15986299
TI  - [Survey of parents of children with cancer who look for alternative therapies].
AB  - Alternative therapies are regimens that run counter to the mainstream of Western
      medicine. The main purpose of this study was to investigate and evaluate the
      alternative medicine with which parents of children with cancer seek to have
      their children treated. The research took as its subjects the parents of children
      with cancer who were outpatients or inpatients in six medical centers from
      September to December, 1999. Data were collected by questionnaire and 110 copies
      were effective. The results showed that 69.1% of the parents had been seeking
      alternative therapies. The most popular form of alternative therapy identified by
      this research was folk and religious therapy (68.4%), followed by Chinese medical
      treatment (57.9%), followed by special diets (50.0%). Other forms were used, such
      as herbal and arcanum therapy (13.2%), human electricity (3.9%), meditation
      (1.3%), and aromatherapy (1.3%). The results also showed that 61.8% of the
      parents had not discussed the use of the alternative therapies with the
      children's doctors. Hospital workers, therefore, should try to understand the
      situations of pediatric patients using alternative therapies, and provide
      appropriate suggestions to parents of pediatric patients as well as more humane,
      thoughtful medical care.

PMID- 15986300
TI  - [Improving procedures for treating domestic violence victims in a local
      hospital].
AB  - The aim of this project was to improve the handling of cases of domestic violence
      by a local hospital. Through the project, medical personnels may gain an improved
      understanding of this problem and increase their ability and knowledge in
      relation to domestic violence. The hope was to provide professional medical
      services while protecting the personal privacy of the patients who needed to be
      helped. Our previous observations had led us to note that there was inadequate
      recognition of domestic violence, inadequate keeping of medical records, no
      standardized working protocol and an environment that was not sufficiently secure
      and safe for victims of domestic violence. During the project, several
      improvements were made, including the setting up of a one-stop service counter, a
      standard working protocol, a design for a safer environment and advanced training
      for medical personnel dealing with cases of domestic violence, and the creation
      of a special form of medical document for domestic violence. The results showed
      improved understanding of the problem among nursing staff, from an initial 58% to
      97%. The satisfaction rate among patients was also elevated, from 55% to 85%.
      Thus with this project, we hope to help victims of domestic violence to banish
      their unpleasant memories early on, to obtain proper medical care both physically
      and psychologically, and finally to benefit from an improved quality of service
      provided by a local hospital, the professional image of whose nursing stuff has
      also been enhanced.

PMID- 15986301
TI  - [The design and content validity of an infection control health education program
      for adolescents with cancer].
AB  - The purpose of this article is to describe the process of designing an Infection
      Control Health Education Program (ICP) for adolescents with cancer, to describe
      the content of that program, and to evaluate its validity. The program consisted
      of an audiovisual "Infection Control Health Education Program in Video Compact
      Disc (VCD)" and "Self-Care Daily Checklist (SCDC)". The VCD was developed from
      systematic literature reviews and consultations with experts in pediatric
      oncology care. It addresses the main issues of infection control among
      adolescents. The content of the SCDC was designed to enhance adolescents' self
      care capabilities by means of twice daily self-recording. The response format for
      content validity of the VCD and SCDC was a 5-point Likert scale. The mean score
      for content validity was 4.72 for the VCD and 4.82 for the SCDC. The percentage
      of expert agreement was 99% for the VCD and 98% for the SCDC. In summary, the VCD
      was effective in improving adolescents' capacity for self-care and the extensive
      reinforcement SCDC was also shown to be useful. In a subsequent pilot study, the
      authors used this program to increase adolescent cancer patients' self-care
      knowledge and behavior for, and decrease their levels of secondary infection.

PMID- 15986302
TI  - [Non-invasive therapeutics in female urinary incontinence by extracorporeal
      magnetic innervation (ExMI)].
AB  - The prevalence of female urinary incontinence (UI) in Taiwan is 19~35% and the
      condition has a psychosocial impact. It is important to prevent UI and to treat
      it when it does occur. It is an intractable symptom which is not very responsive
      to medicine or surgery, although in the past, these were the most common options
      for treating it. The alternatives include pelvic floor muscle exercises, vaginal
      cone weight training, functional electrical stimulation and biofeedback. The
      effectiveness of these methods depends on the patient's motivation and
      compliance, as well as on health care providers' encouragement. However, the
      Extracorporeal Magnetic Innervation (ExMI) is simple and easy to use and
      therefore enhances participants' motivation and compliance. The authors review
      the relevant literature and describe the development of the revolutionary new
      treatment and discuss its effectiveness concluding that its clinical
      effectiveness needs further evaluation.

PMID- 15986303
TI  - [A comparison of action research, participatory research, and participatory
      action research and their applications in nursing research].
AB  - Action research, participatory research, and participatory action research
      methodology adopting critical theory as epistemology for knowledge development
      have been applied in diverse nursing specialties. They share similar research
      principles and values, and employ the same data collection methods. For these
      many scholars use the terms interchangeably. However, their developmental origins
      and ideological backgrounds are different, as are their expected outcomes and
      research methods. The terms have therefore been misused. This paper is intended
      to enhance researchers' ability to distinguish between the similar methodologies
      and to apply research methodology and related terms appropriately to the relevant
      issues of health care.

PMID- 15986304
TI  - [The application of qi-gong therapy to health care].
AB  - A great number of clinical studies merging traditional Chinese medicine (TCM) and
      Western medicine have proved the complementary healing effects of qi-gong in
      medical science. Traditional Chinese respiration exercises help to regulate our
      mind, body and breathing and coordinate our internal organs, remove toxins and
      enhance immunity. Domestic and foreign studies indicate that qi-gong can relieve
      chronic pain, reduce tension, increase activities of phagocytes in coenocytes,
      improve cardiopulmonary function, improve eyesight, influence the index of blood
      biochemistry, etc. Due to the obvious healing effects of qi-qong therapy, through
      introducing qi-gone concepts and related medical research, this paper aims to
      inspire health care workers to integrate qi-qong therapy into medical treatments
      and nursing care, or to carry out further studies in order to make good the
      shortfall in provision of holistic medicine and nursing in the interests of the
      quality of patient care.

PMID- 15986305
TI  - [Sleep hygiene for female nurses].
AB  - Sleep is a basic human need. A good night's sleep shapes our physical and mental
      health. Female nurses experience particularly complex sleep disturbance problems
      because of after working rotating shifts, as well as because of the effects of
      the female reproductive hormones. Both issues present a challenge to the
      understanding of female nurses' sleep. This paper summarizes the existing
      knowledge about sleep in women, including shift workers in relation to their
      reproductive status, and introduces practical sleep hygiene concepts and
      strategies for female nurses.

PMID- 15986306
TI  - [From health promoting school perspectives to discuss the building of school
      community partnership].
AB  - In the wake of the WHO's health promotion campaign health promotion schools have
      gained currency in Europe and the United States. The Department of Education in
      Taiwan has proposed a "school health promotion program" and the Department of
      Health a "program to build healthy schools" The goal of these programs was to
      create a holistic environment for school health and put the concepts of "school
      family-community partnership" into practice. Although difficulties, such as
      school-centered perspectives, ambiguous definitions of "community" and shortage
      of funding, human resources and long-term planning impeded the program, this
      article, based on literature and practical experience, presents the "school
      community model" and the strategies that it applied to organize the school
      community health promotion committee to plan long-term programs and to assess the
      needs and resources of schools and communities on a collaborative basis. It
      contends, furthermore, that integrating community services into curriculums in
      order to enable students to appreciate the meaning of partnership, and involving
      the community in the planning process, can achieve the goal of effectively
      promoting the health of both the school and the community.

PMID- 15986307
TI  - [An experience nursing a patient with amyotrophic lateral sclerosis using the
      theory of self-care].
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive and lethal motor
      neurodegenerative disease. The cause of the disease is unknown, and there is no
      cure current clinical treatment methods include Riluzole and supportive therapy.
      However, Riluzole only decelerates the patient's muscle strength loss and
      prolongs survival by about 3-5 months (Aventis Pharmaceutical, 2004). The patient
      will die eventually because of aspiration pneumonia or respiratory failure. This
      paper documents the use of Orem's self-care theory and holistic nursing
      assessment in a patient with amyotrophic lateral sclerosis. There are four areas
      of nursing concern: impaired self-care ability (dressing, feeding, toileting, and
      bathing), risk of falls, impaired verbal communication, and powerlessness. In
      terms of these problems suitable nursing activities are provided to develop the
      patient's ability to care for himself, prevent accidents, promote skills of non
      verbal communication, and alleviate powerlessness in order to strengthen control.

PMID- 15986308
TI  - [An experience nursing a patient with ovarian hyperstimulation syndrome who has
      undergone artificial fertilization treatment].
AB  - With the growing incidence of infertility in the modern world, artificial
      fertilization techniques provide new hope for many would-be parents. However,
      side-effects of the treatment can have a huge impact on patients and their
      families. This article employs Roy's adaptation model to study a patient with
      ovarian hyperstimulation syndrome who had undergone artificial fertilization
      treatment. Under careful assessment and examination, the author discovered that
      the patient suffered from such problems as malnutrition, fluid overload, pain and
      lethargy, etc. By employing skillful communication techniques and the display of
      empathy, the author helped to alleviate the patient's sufferings during
      treatment, as well as providing professional knowledge and advice. To help the
      patient in resolving difficulties that might have been encountered in the family,
      the author also exercised the idea of the family as core. The author hopes to
      share the knowledge that, in the care of patients with infertility, it is vital
      that health care professionals look after their psychological requirements as
      well as their physical care, in order to provide optimum care.

PMID- 15986309
TI  - Using SERVQUAL to evaluate quality disconfirmation of nursing service in Taiwan.
AB  - The purpose of this study was to determine the extent of disconfirmation of the
      perceived quality of nursing services, and its relationship to patient's
      satisfaction, intent to return, and intent to recommend to others. The service
      dimensions were tangibles, reliability, responsiveness, assurance, and empathy,
      which were adopted from the Gap model of Parasuraman, Zeithaml and Berry (1985).
      A total of 186 subjects was tested by a modified SERVQUAL (service quality)
      instrument. These subjects were from 15 randomly selected medical-surgical units
      in a medical center in Taipei, Taiwan, Republic of China. The response rate was
      92%. Descriptive statistics and multiple regression were used to analyze
      subjects' responses. A number of the demographic variables served as covariates
      in data analysis. Responsiveness was highly significant in predicting overall
      satisfaction with hospital service (p = .0003). Reliability was significant in
      predicting overall satisfaction with nursing care (p < .00005) and intent to
      return. Empathy was a highly significant predictor of intent to recommend.

PMID- 15986310
TI  - A comparison, by quantitative and qualitative methods, between the self
      management behaviors of parents with asthmatic children in two hospitals.
AB  - This study compared the self-management behaviors of parents with asthmatic
      children staying in two hospitals and explored barriers to self-management
      behaviors by interviewing. 227 parents were recruited for quantitative analysis
      by completing a self-report structured questionnaire, 94 of these parents were
      from the Taipei area and 133 were from the Taoyuan area. Sixteen parents were
      interviewed from this population. The results indicated that the parents in
      theTaoyuan area had younger age, lower socioeconomic status (SES), and higher
      exercise limitations for children. Their knowledge, enabling factors, and self
      management behaviors were also lower than their counterparts in the Taipei area.
      The determining factors of self-management behaviors were socioeconomic status,
      self-efficacy, sources of education, and perceived effectiveness (Adjusted R2=
      .593) in 227 parents. Six major themes about the influencing factors of self
      management were deduced from the interview data: lack of understanding and
      dislike of the asthma label, less self-perceived severity, lack of understanding
      about asthma medication, lack of confidence in environmental controls, financial
      burden of anti-mite products, and doubt about effectiveness. Three major barriers
      to self-management behaviors of parents in the Taoyuan area were inconsistent use
      of alternative treatments, overdependence on medical service, and lack of use of
      peak flow meter. Parents with asthmatic children living in the Taoyuan area had
      poorer self-management behaviors than those in the Taipei area, and SES was one
      of the determining factors. The health beliefs of Taoyuan parents included many
      misconceptions. Conducting the educational needs assessment through quantitative
      and qualitative methods could provide proficiency information for designing
      educational content appropriate to specific populations.

PMID- 15986311
TI  - Exercise stage and processes of change in patients with chronic obstructive
      pulmonary disease.
AB  - This study uses a horizontal investigative method; the purpose of this study was
      the application of the transtheoretical model to the exercise behavior of
      patients with chronic obstructive pulmonary disease (COPD). Constructed
      questionnaires were utilized to interview the subjects; the questionnaires
      contained personal demographics, stages of exercise, and processes of change.
      Purposive sampling was conducted at a medical center in Southern Taiwan. Ninety
      eight valid questionnaires were collected. Subjects ranged 39-83 years of age (M
      = 68.1, SD = 10.4). Exercise activities in the sample were divided between pre
      contemplation (25.5%), contemplation (2%), preparation (21.4%), action (4.1%),
      and maintenance (46.9%). Walking proved the most common exercise method. For
      processes of change, the ranked top was counter-conditioning indicating that COPD
      patients most frequently sought alternative activities to replace status of no
      exercise. In terms of interrelations between ten processes and five stages, the
      precontemplation stage scored manifestly lower on processes of change than any
      other stage. The findings of this study provide guidance to clinical
      practitioners in developing stage-matched interventions, promotional strategies
      with a variety of program planning, and suggestions for research agencies in the
      future.

PMID- 15986312
TI  - Stress, coping, and psychological health of vocational high school nursing
      students associated with a competitive entrance exam.
AB  - An important issue for the nursing education system in Taiwan is to reinforce
      nursing education to enhance competence levels for entry to nursing specialties.
      Consequently, to meet the prospective demands of technical manpower, not only do
      nursing students in college and vocational schools pursue further studies, but
      they also take competitive entrance exams. Using a descriptive cross-sectional
      design, the study examined the following among nursing students in vocational
      high schools: (1) perception and sources of entrance exam stress and use of
      coping behaviors; (2) the effect of difference in entrance exam stress levels on
      coping behaviors used, and (3) measurement of coping function to determine which
      coping behavior works best for buffering the impact of stress on psychological
      health during a preparatory stage of a college and university entrance exam. The
      subjects were 441 third-year nursing students of vocational high schools in
      northern Taiwan, recruited by convenience sampling. Three measurements were
      adopted: Stress perceived scale, Coping behavior inventory, and a Chinese health
      questionnaire. Results showed that the five main stressors of entrance exam
      stress, in descending order, were taking tests, the student's own aspirations,
      learning tasks, teacher's aspirations and parent's aspirations. Students
      generally used problem-focused coping strategies including optimistic action and
      social support to deal with the entrance exam stress, but use of emotion-focused
      coping strategies including avoidance and emotional disturbance was significantly
      increased as perceived level of stress rose. Two-way analyses of variance (2-way
      ANOVA) revealed that problem-focused coping had a positive main effect of
      alleviating psychological distress. A significant interaction was observed
      between stress perceived and problem-focused coping used for psychological
      health. Further examination of the interaction effect showed that problem-focused
      coping behaviors were potentially more adaptive in relation to psychological
      health at the lower and moderate stress levels (25 - 75%T) than that at the
      extreme stress level (> 75%T). Conversely, emotion-focused coping had a negative
      main effect or impairing psychological health. No interaction effect was found
      between stress perceived and emotion-focused coping used, suggesting that the
      relationship between emotion-focused coping and psychological distress was
      consistent across various stress levels.

PMID- 15986313
TI  - Identifying factors associated with hospital readmissions among stroke patients
      in Taipei.
AB  - Hospital readmissions contribute significantly to the cost of medical care, and
      may reflect unresolved problems at discharge or a lack of resources in post
      hospital care. The purpose of this paper is to assess the effects of patient
      characteristics at discharge, the need for nursing care, discharge planning
      program, post-hospital care arrangements, and caregiver characteristics on
      readmissions of stroke patients. Patients discharged from neurological wards in
      seven hospitals in the Taipei area were recruited into the study. Surveys were
      conducted before their discharge, and at one month after discharge. Of the 489
      patients included in the study, 24.3% were readmitted. After controlling for
      other variables, factors associated with readmissions were number of limitations
      in activities of daily living (ADL), first incidence of stroke, the need for
      wound nursing care, the adoption of a care plan, and the discharge locations.
      Contrary to expectation, age, length of stay, counseling before discharge, and
      caregiver burden were not associated with readmissions. The findings of this
      study indicate that ADL limitation is an effective predictor of readmissions.
      Increasing home nursing resources to meet the demand for wound nursing care may
      also be effective in reducing readmissions. Discharging patients into
      institutions for a short period of time may also prove to be more economically
      viable due to the reduction in readmissions.

PMID- 15986314
TI  - An exploratory study of Taiwanese consumers' experiences of using health-related
      websites.
AB  - It is manifest that the rapid growth of Internet use and improvement of
      information technology have changed our lifestyles. In recent years, Internet use
      in Taiwan has increased dramatically, from 3 million users in 1998 to
      approximately 8.6 million by the end of 2002. The statistics imply that not only
      health care professionals but also laypersons rely on the Internet for health
      information. The purpose of this study was to explore Taiwan consumers'
      preferences and information needs, and the problems they encountered when getting
      information from medical websites. Using simple random sampling and systematic
      random sampling, a survey was conducted in Taipei from August 26, 2002 to October
      30, 2002. Using simple random sampling and systematic random sampling, 28
      boroughs (Li) were selected; the total sample number was 1043. Over one-quarter
      (26.8 %) of the respondents reported having never accessed the Internet, while
      763 (73.2%) reported having accessed the Internet. Of the Internet users, only
      396 (51.9%) had accessed health-related websites, and 367 (48.1%) reported having
      never accessed health-related websites. The most popular topics were disease
      information (46.5%), followed by diet consultation (34.8%), medical news (28.5%),
      and cosmetology (28.5%). The results of the survey show that a large percentage
      of people in Taiwan have never made good use of health information available on
      the websites. The reasons for not using the websites included a lack of time or
      Internet access skills, no motivation, dissatisfaction with the information,
      unreliable information be provided, and inability to locate the information
      needed. The author recommends to enhance health information access skills,
      understand the needs and preferences of consumers, promote the quality of medical
      websites, and improve the functions of medical websites.

PMID- 15986315
TI  - The effects of staff nurses' morale on patient satisfaction.
AB  - This study, designed by descriptive and inferential methods, study aimed to
      examine staff nurses' morale and its effect on patient satisfaction, the most
      commonly used variable to measure patient outcomes. Data were collected with
      structured questionnaires from 332 nurses and 265 inpatients in 21 medical
      surgical units of a medical center in Taiwan. All registered nurses (RN) among
      the 21 sample units were recruited and administered with Litwin and Stringerm's
      (1968) Work Morale Scale, which was modified by Hsu in 1981. A convenience
      sampling was implemented to select those patients who had been admitted for at
      least 3 days and were ready to be discharged. Yang's (1997) Nursing-Sensitive
      Patient Satisfaction Scale was used to measure patient outcomes. The results
      showed that job position and pay had a significant effect on nurses' work morale.
      Nurses' work morale may not necessarily be an impact factor on patient
      satisfaction, but it accounts for 66.7 percent of the discriminate power to
      predict nursing-sensitive patient satisfaction. In view of the findings, every
      attempt should be made to highlight the nature of a caring profession. Nursing
      leaders should put effort into improving nurses' involvement and identification
      with their organizations, both of which are significant factors associated with
      nursing unit morale. The findings of this study may contribute to a body of
      knowledge regarding nurses' work morale and nursing-sensitive patient outcomes.

PMID- 15986316
TI  - Exploring quality of sleep and its related factors among menopausal women.
AB  - Sleep, a basic physiological need of all humans, appears to be both integrative
      and restorative. However, studies have reported that 33-51% of women show a
      dramatic increase in sleep disturbance in the mid-life years, a time when they
      enter menopause. The purposes of this study were to (1) explore the prevalence of
      poor sleep quality in menopausal women; (2) identify the relationship between
      sleep quality of menopausal women and its related factors; (3) predict the
      possible explanations of how the related variables affect sleep quality of
      menopausal women; and (4) provide recommendations for future strategies that aim
      to improve sleep quality of menopausal women. A cross-sectional, correlation
      coefficient design was used. Purposive sampling was employed to recruit 197
      menopause women from a small town in central Taiwan. T-test, one-way ANOVA, and
      multiple regression were used for data analysis. The results were as follows: (1)
      overall, the total score for sleep quality was 5.55 +/- 3.47; 57.9% of subjects
      were identified as good sleepers and 42.1% as poor sleepers; (2) there were
      significant differences in quality of sleep related to occupational situation,
      history of chronic disease, menopausal status, number of chronic diseases, and
      number of menopausal symptoms (t = - 3.49, - 3.37, p < .01; F = 3.62, p < .05, F
      = 4.95, 5.35, p < .01); (3) depression and aging were strongly related to quality
      of sleep (r = .57; .22, p < .01); (4) 36% of variance in quality of sleep can be
      explained by depression and aging.

PMID- 15986317
TI  - Identification of risk and age-at-onset genes on chromosome 1p in Parkinson
      disease.
AB  - We previously reported a linkage region on chromosome 1p (LOD = 3.41) for genes
      controlling age at onset (AAO) in Parkinson disease (PD). This region overlaps
      with the previously reported PARK10 locus. To identify the gene(s) associated
      with AAO and risk of PD in this region, we first applied a genomic convergence
      approach that combined gene expression and linkage data. No significant results
      were found. Second, we performed association mapping across a 19.2-Mb region
      centered under the AAO linkage peak. An iterative association mapping approach
      was done by initially genotyping single-nucleotide polymorphisms at an average
      distance of 100 kb apart and then by increasing the density of markers as needed.
      Using the overall data set of 267 multiplex families, we identified six
      associated genes in the region, but further screening of a subset of 83 families
      linked to the chromosome 1 locus identified only two genes significantly
      associated with AAO in PD: the gamma subunit of the translation initiation factor
      EIF2B gene (EIF2B3), which was more significant in the linked subset and the
      ubiquitin-specific protease 24 gene (USP24). Unexpectedly, the human
      immunodeficiency virus enhancer-binding protein 3 gene (HIVEP3) was found to be
      associated with risk for susceptibility to PD. We used several criteria to define
      significant results in the presence of multiple testing, including criteria
      derived from a novel cluster approach. The known or putative functions of these
      genes fit well with the current suspected pathogenic mechanisms of PD and thus
      show great potential as candidates for the PARK10 locus.

PMID- 15986318
TI  - Weighting affected sib pairs by marker informativity.
AB  - For the analysis of affected sib pairs (ASPs), a variety of test statistics is
      applied in genomewide scans with microsatellite markers. Even in multipoint
      analyses, these statistics might not fully exploit the power of a given sample,
      because they do not account for incomplete informativity of an ASP. For meta
      analyses of linkage and association studies, it has been shown recently that
      weighting by informativity increases statistical power. With this idea in mind,
      the first aim of this article was to introduce a new class of tests for ASPs that
      are based on the mean test. To take into account how much informativity an ASP
      contributes, we weighted families inversely proportional to their marker
      informativity. The weighting scheme is obtained by use of the de Finetti
      representation of the distribution of identity-by-descent values. We derive the
      limiting distribution of the weighted mean test and demonstrate the validity of
      the proposed test. We show that it can be much more powerful than the classical
      mean test in the case of low marker informativity. In the second part of the
      article, we propose a Monte Carlo simulation approach for evaluating significance
      among ASPs. We demonstrate the validity of the simulation approach for both the
      classical and the weighted mean test. Finally, we illustrate the use of the
      weighted mean test by reanalyzing two published data sets. In both applications,
      the maximum LOD score of the weighted mean test is 0.6 higher than that of the
      classical mean test.

PMID- 15986322
TI  - High-risk carotid endarterectomy.
AB  - "High-risk" carotid endarterectomy (CEA): fact or fiction? To answer this
      question we reviewed the available evidence starting from controlled randomized
      trials, through retrospective population- and large institution-based studies to
      case-series. CEA can be performed in most "high-risk" patients with low mortality
      and morbidity. A broad concept of high-risk CEA, based merely on exclusion from
      previous controlled randomized CEA trials, cannot be justified. The vast majority
      of evidence suggests that age (> or =80 years) per se should not be considered a
      high-risk criterion for CEA. However, it appears that there are certain
      individual risk factors, which may influence outcome adversely. It appears that
      CEA in the setting of contralateral carotid occlusion may be associated with very
      slightly increased risk of adverse perioperative events. Local risk factors,
      namely carotid reoperation and CEA following prior cervical radiation therapy,
      are associated with slightly increased stroke, death and probably cranial nerve
      injury rates. If these risk factors are frequent in a particular series the
      overall outcome of CEA will be worse. In the absence of level-one evidence on the
      long-term efficacy of carotid artery stenting (CAS) in stroke prophylaxis,
      selection for CAS should be restricted to well-defined high-risk categories, such
      as severe medical comorbidities or local-anatomic risk factors.

PMID- 15986323
TI  - Optimal training strategies for carotid stenting.
AB  - Future participation in the treatment of carotid occlusive disease is dependent
      on training to perform carotid stent placement. Reviewed herein are strategies
      for training in carotid stenting. Included in this discussion are; the skills
      required for carotid stenting, the carotid stent learning curve, a comparison of
      training and credentialing, and the roles of simulators, courses, and hands-on
      experience in carotid stent training.

PMID- 15986324
TI  - Utility of MRA and CTA in the evaluation of carotid occlusive disease.
AB  - Cervical carotid artery atherosclerotic disease is an important cause of
      thromboembolic stroke. Noninvasive imaging techniques have become preferred in
      initial diagnostic workup. We review the current approach to carotid imaging, and
      the clinical utility and limitations of carotid computed tomography angiography
      (CTA) and magnetic resonance angiography (MRA). Future directions of these
      modalities, including carotid plaque imaging, are also discussed.

PMID- 15986325
TI  - Carotid angiography in contemporary vascular surgery practice.
AB  - While most patients with carotid artery disease can safely undergo carotid
      endarterectomy based on duplex ultrasound alone, carotid angioplasty and stenting
      must, by its nature, be performed in conjunction with carotid arteriography. The
      techniques of carotid angiography are a necessary prerequisite to carotid
      intervention. The indications, technique, and results of carotid angiography in a
      contemporary vascular surgery practice are described.

PMID- 15986326
TI  - Current indications, results, and technique of carotid angioplasty/stenting.
AB  - Carotid endarterectomy (CEA) remains the treatment of choice for most patients
      with high-grade carotid artery stenosis. Certain patient subsets, including those
      with severe cardiac and pulmonary disease and those with local/anatomic risk
      factors (including recurrent stenosis following CEA, cervical radiation therapy,
      prior radical neck dissection, and surgically inaccessible lesions) are at
      increased risk of stroke, cranial nerve injury and non-Q myocardial infarction
      following CEA, and may be better served by carotid angioplasty and stenting
      (CAS). Procedural success is dependent upon proper patient selection and
      meticulous attention to detail. The use of cerebral embolic protection appears to
      reduce the risk of peri-procedural stroke following CAS.

PMID- 15986327
TI  - Cerebral embolic protection.
AB  - Carotid angioplasty and stenting (CAS) is rapidly evolving into a viable
      alternative to carotid endarterectomy (CEA). This has been possible due to
      advances in endoluminal equipment and the development of mechanical cerebral
      embolic protection devices. Theoretically, these various devices reduce the
      occurrence of distal embolization into the intracranial circulation and thereby
      minimize the clinical consequence of a cerebrovascular accident. Embolic
      protection systems are currently classified into three main categories depending
      on the mechanism: 1) distal occlusion; 2) distal filtration; and 3) proximal
      occlusion. This review will provide a framework with regard to these devices with
      some specific examples cited.

PMID- 15986328
TI  - Neurovascular rescue.
AB  - Neurovascular complications of carotid artery stenting (CAS) include intracranial
      embolism and hemorrhage, carotid dissection, in-stent thrombosis and vasospasm.
      Management of these crises requires knowledge of the intracranial vascular
      anatomy and collateral circulation, correct identification of the complication
      and its clinical implications, and a response plan that is appropriate to the
      complication and to the skill set of the operator. In this chapter the authors
      discuss techniques for the avoidance and management of CAS procedural
      complications.

PMID- 15986329
TI  - Credentialing in carotid angiography and carotid angioplasty/stenting: experience
      of Mayo Clinic Rochester.
AB  - Carotid angioplasty and stenting is an evolving technique in the treatment of
      patients with carotid occlusive disease who are at increased risk for carotid
      endarterectomy. The literature has largely focused on the short and long-term
      results of this novel procedure. Due to the involvement of multiple disciplines,
      all of whom have legitimate claims to the carotid territory, credentialing has
      been a contentious issue at the local hospital level. This article describes the
      experience of Mayo Clinic Rochester in developing, in a multi-disciplinary
      manner, documents for credentialing in carotid angiography, carotid intervention,
      and guidelines for the use of this novel procedure.

PMID- 15986330
TI  - Probing heat-stable water-soluble proteins from barley to malt and beer.
AB  - Proteins determine the quality of barley in malting and brewing end-uses. In this
      regard, water-soluble barley proteins play a major role in the formation,
      stability, and texture of head foams. Our objective was to survey the barley seed
      proteins that could be involved in the foaming properties of beer. Therefore, two
      dimensional (2-D) electrophoresis and mass spectrometry were combined to
      highlight the barley proteins that could resist the heating treatments occurring
      during malting and brewing processes. As expected, from barley to malt and to
      beer, most of the heat-stable proteins are disulfide-rich proteins, implicated in
      the defense of plants against their bio-aggressors, e.g., serpin-like
      chymotrypsin inhibitors (protein Z), amylase and amylase-protease inhibitors, and
      lipid transfer proteins (LTP1 and LTP2). For LTP1s, the complex pattern displayed
      in 2-D electrophoresis could be related to some chemical modifications already
      described elsewhere, such as acylation or glycation through Maillard reactions,
      which occur on malting. Our proteomics approach allowed the identification of the
      numerous proteins present in beer in addition to the major ones already
      described. The involvement of these proteins in the quality of beer foam can now
      be evaluated.

PMID- 15986331
TI  - Identification and relative quantification of membrane proteins by surface
      biotinylation and two-dimensional peptide mapping.
AB  - Membrane proteins play a central role in biological processes, but their
      separation and quantification using two-dimensional gel electrophoresis is often
      limited by their poor solubility and relatively low abundance. We now present a
      method for the simultaneous recovery, separation, identification, and relative
      quantification of membrane proteins, following their selective covalent
      modification with a cleavable biotin derivative. After cell lysis, biotinylated
      proteins are purified on streptavidin-coated resin and proteolytically digested.
      The resulting peptides are analyzed by high-pressure liquid chromatography and
      mass spectrometry, thus yielding a two-dimensional peptide map. Matrix assisted
      laser desorption/ionization-time of flight signal intensity of peptides, in the
      presence of internal standards, is used to quantify the relative abundance of
      membrane proteins from cells treated in different experimental conditions. As
      experimental examples, we present (i) an analysis of a BSA-spiked human embryonic
      kidney membrane protein extract, and (ii) an analysis of membrane proteins of
      human umbilical vein endothelial cells cultured in normoxic and hypoxic
      conditions. This last study allowed the recovery of the vascular endothelial
      cadherin/actin/catenin complex, revealing an increased accumulation of beta
      catenin at 2% O(2) concentration.

PMID- 15986332
TI  - Comparative proteomic analysis of esophageal squamous cell carcinoma.
AB  - Ranking as the fourth commonest cancer, esophageal squamous cell carcinoma (ESCC)
      represents one of the leading causes of cancer death in China. One of the main
      reasons for the low survival rate is that neoplasms in esophagus are not detected
      until they have invaded into surrounding tissues or spread throughout the body at
      advanced stages. A better understanding of the malignant mechanism and early
      diagnosis are important for fighting ESCC. In this study, we used proteomics to
      analyze ESCC tissues, aiming at defining the proteomic features implicated in the
      multistage progression of esophageal carcinogenesis. Proteins that exhibited
      significantly different expressions were identified by peptide mass
      fingerprinting and validated by Western blotting and reverse transcriptase
      polymerase chain reaction. The protein changes were then correlated to the
      different grades of disease differentiation. Compared to those in adjacent normal
      epitheliums, the expression of 15 proteins including enolase, elongation factor
      Tu, isocitrate dehydrogenase, tubulin alpha-1 chain, tubulin beta-5 chain, actin
      (cytoplasmic 1), glyceraldehyde-3 phosphate dehydrogenase, tropomyosin isoform 4
      (TPM4), prohibitin, peroxiredoxin 1 (PRX1), manganese-containing superoxide
      dismutase (MnSOD), neuronal protein, and transgelin was up-regulated; and the
      expression of five proteins including TPM1, squamous cell carcinoma antigen 1
      (SCCA1), stratifin, peroxiredoxin 2 isoform a, and alpha B crystalline was down
      regulated in cancer tissues with a statistical significance (p < 0.05). In
      addition, the differential expression of SCCA1, PRX1, MnSOD, TPM4, and prohibitin
      can be observed in precancerous lesions of ESCC. The expression of stratifin,
      prohibitin, and SCCA1 dropped with increasing dedifferentiation of ESCC. These
      data may suggest that these proteins contribute to the multistage process of
      carcinogenesis, tumor progression, and invasiveness of ESCC.

PMID- 15986333
TI  - Improving feature detection and analysis of surface-enhanced laser
      desorption/ionization-time of flight mass spectra.
AB  - Discovering valid biological information from surface-enhanced laser
      desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) depends on
      clear experimental design, meticulous sample handling, and sophisticated data
      processing. Most published literature deals with the biological aspects of these
      experiments, or with computer-learning algorithms to locate sets of classifying
      biomarkers. The process of locating and measuring proteins across spectra has
      received less attention. This process should be tunable between sensitivity and
      false-discovery, and should guarantee that features are biologically meaningful
      in that they represent chemical species that can be identified and investigated.
      Existing feature detection in SELDI-TOF MS is not optimal for acquiring
      biologically relevant data. Most methods have so many user-defined settings that
      reproducibility and comparability among studies suffer considerably. To address
      these issues, we have developed an approach, called simultaneous spectrum
      analysis (SSA), which (i) locates proteins across spectra, (ii) measures their
      abundance, (iii) subtracts baseline, (iv) excludes irreproducible measurements,
      and (v) computes normalization factors for comparing spectra. SSA uses only two
      key parameters for feature detection and one parameter each for quality
      thresholds on spectra and peaks. The effectiveness of SSA is demonstrated by
      identifying proteins differentially expressed in SELDI-TOF spectra from plasma of
      wild-type and knockout mice for plasma glutathione peroxidase. Comparing analyses
      by SSA and CiphergenExpress Data Manager 2.1 finds similar results for large
      signal peaks, but SSA improves the number and quality of differences betweens
      groups among lower signal peaks. SSA is also less likely to introduce systematic
      bias when normalizing spectra.

PMID- 15986334
TI  - A two-dimensional electrophoretic map of human mitochondrial proteins from
      immortalized lymphoblastoid cell lines: a prerequisite to study mitochondrial
      disorders in patients.
AB  - Mitochondrial diseases may be caused by numerous mutations that alter proteins of
      the respiratory chain and of other metabolic pathways in the mitochondrium. For
      clinicians this disease group poses a considerable diagnostic challenge due to
      ambiguous genotype-phenotype relationships. Until now, only 30% of the
      mitochondriopathies can be diagnosed at the molecular level. We therefore need a
      new diagnostic tool that offers a wide view on the mitochondrial proteins. Here,
      we present a method to generate a high-resolution, large-gel two-dimensional gel
      electrophoretic (2-DE) map of a purified fraction of mitochondrial proteins from
      Epstein-Barr virus-immortalized lymphoblastoid cell line (LCL). LCLs can be
      easily obtained from patients and control subjects in a routine clinical setting.
      They often express the biochemical phenotype and can be cultured to high cell
      numbers, sufficient to gain enough purified material for 2-DE. In total we
      identified 166 mitochondrial proteins. Thirteen proteins were earlier not known
      to be of mitochondrial origin. Thirty-nine proteins were associated with human
      diseases ranging from respiratory chain enzyme deficiencies to disorders of beta
      oxidation and amino acid metabolism. This 2-DE map is intended to be the first
      step to diagnose mitochondrial diseases at the proteomic level.

PMID- 15986335
TI  - Correlation-associated peptide networks of human cerebrospinal fluid.
AB  - Profiling of peptides and small proteins from either human body fluids or tissues
      by chromatography and subsequent mass spectrometry reveals several thousand
      individual peptide signals per sample. Any peptide is an intermediate in the
      course of biosynthesis, post-translational modification (PTM), proteolytic
      processing and degradation. Changes in the concentration of one peptide often
      affects the concentration of the other, hence a challenge consists in the
      development of suitable tools to turn this large amount of data into biologically
      relevant information. Comprehensive statistical analysis of the peptide profiling
      data allows associating peptides, which are closely related in terms of peptide
      biochemistry. Here, the bioinformatic concept of peptide networks, correlation
      associated peptide networks (CANs), is introduced. Peptides with statistical
      similarity of their concentrations are grouped in form of networks, and these
      networks are interpreted in terms of peptide biochemistry. The spectrum of
      functional relationships found in cerebrospinal fluid CAN covers PTM and
      proteolytic degradation of peptides, clearance processing in the complement
      cascade, common secretion of peptides by neuroendocrine cells as well as
      ubiquitin-mediated degradation. Our results indicate that CAN is a powerful
      bioinformatic tool for the systematic analysis and interpretation of large
      peptidomics and proteomics data and helps to discover novel bioactive and
      diagnostic peptides.

PMID- 15986336
TI  - Toll-like receptor 2 and toll-like receptor 4 expression on CD64+ monocytes in
      rheumatoid arthritis: comment on the article by Iwahashi et al.

PMID- 15986337
TI  - Clinical images: Anetoderma in systemic lupus erythematosus with antiphospholipid
      antibodies.

PMID- 15986339
TI  - PTPN22 and rheumatoid arthritis: gratifying replication.

PMID- 15986340
TI  - The many worlds of reducing interleukin-1.

PMID- 15986341
TI  - How should treatment effect on spinal radiographic progression in patients with
      ankylosing spondylitis be measured?

PMID- 15986342
TI  - Invasiveness of fibroblast-like synoviocytes is an individual patient
      characteristic associated with the rate of joint destruction in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by inflammation and
      destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from
      synovial tissue of patients with RA can invade normal human cartilage in severe
      combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in
      vitro. This study was undertaken to investigate the association of these in vitro
      characteristics with disease characteristics in patients with RA. METHODS:
      Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were
      obtained. Samples of different joints were collected from 7 patients with RA. The
      FLS invasiveness in Matrigel was studied, and the intraindividual and
      interindividual differences were compared. From the patients with FLS who
      exhibited the most extreme differences in in vitro ingrowth (most and least
      invasive FLS), radiographs of the hands and feet were collected and scored
      according to the Sharp/van der Heijde method to determine the relationship
      between in vitro invasion data and estimated yearly joint damage progression.
      RESULTS: FLS from patients with RA were more invasive than FLS from patients with
      OA (P < 0.001). The mean intraindividual variation in FLS invasion was much less
      than the mean interindividual variation (mean +/- SD 1,067 +/- 926 and 3,845 +/-
      2,367 for intraindividual and interindividual variation, respectively; P =
      0.035), which shows that the level of FLS invasion is a patient characteristic.
      The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the
      disease duration was 4.4 +/- 1.1 units per year of disease duration in patients
      with the least invasive FLS (n = 9), which was much lower compared with the 21.8
      +/- 3.1 units per year of disease duration in patients with the most invasive FLS
      (n = 9) (P < 0.001). CONCLUSION: The ex vivo invasive behavior of FLS from RA
      patients is associated with the rate of joint destruction and is a patient
      characteristic, given the much smaller intraindividual than interindividual FLS
      variation.

PMID- 15986343
TI  - Effects of doxycycline on progression of osteoarthritis: results of a randomized,
      placebo-controlled, double-blind trial.
AB  - OBJECTIVE: To confirm preclinical data suggesting that doxycycline can slow the
      progression of osteoarthritis (OA). The primary outcome measure was joint space
      narrowing (JSN) in the medial tibiofemoral compartment. METHODS: In this placebo
      controlled trial, obese women (n = 431) ages 45-64 years with unilateral
      radiographic knee OA were randomly assigned to receive 30 months of treatment
      with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured
      manually in fluoroscopically standardized radiographic examinations performed at
      baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6
      month intervals. RESULTS: Seventy-one percent of all randomized subjects
      completed the trial. Radiographs were obtained from 85% of all randomized
      subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects
      who completed the study per protocol. After 16 months of treatment, the mean +/-
      SD loss of joint space width in the index knee in the doxycycline group was 40%
      less than that in the placebo group (0.15 +/- 0.42 mm versus 0.24 +/- 0.54 mm);
      after 30 months, it was 33% less (0.30 +/- 0.60 mm versus 0.45 +/- 0.70 mm).
      Doxycycline did not reduce the mean severity of joint pain, although pain scores
      in both treatment groups were low at baseline and remained low throughout the
      trial, suggesting the presence of a floor effect. However, the frequency of
      followup visits at which the subject reported a > or = 20% increase in pain in
      the index knee, relative to the previous visit, was reduced among those receiving
      doxycycline. In contrast, doxycycline did not have an effect on either JSN or
      pain in the contralateral knee. In both treatment groups, subjects who reported a
      > or = 20% increase in knee pain at the majority of their followup visits had
      more rapid JSN than those whose pain did not increase. CONCLUSION: Doxycycline
      slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in
      the contralateral knee suggests that pathogenetic mechanisms in that joint were
      different from those in the index knee.

PMID- 15986344
TI  - Lack of support for the presence of an osteoarthritis susceptibility locus on
      chromosome 6p.
AB  - OBJECTIVE: To replicate, in a Northern Irish population, the previously reported
      association between a locus on chromosome 6 and hip osteoarthritis (OA). METHODS:
      Patients with hip OA were identified from a registry of patients who had
      undergone total hip replacement surgery over an 8-year period at a single large
      orthopedic unit in Northern Ireland. Patients identified as index cases were
      contacted by mail and asked to reply only if another family member also had
      undergone total hip replacement surgery. Using this approach, we identified 288
      sibling pairs concordant for primary hip OA. DNA was extracted from peripheral
      blood, and microsatellite markers were amplified by polymerase chain reaction and
      subsequently genotyped. RESULTS: No evidence of linkage to this region was
      demonstrated by either 2-point analysis or multipoint analysis of 17
      microsatellites. CONCLUSION: The reported association between a locus on
      chromosome 6 and hip OA could not be confirmed in this population. Different
      methods of ascertainment and phenotyping of OA may contribute to the current
      inability to replicate genetic associations for hip OA.

PMID- 15986345
TI  - Prevalence of and risk factors for low bone mineral density and vertebral
      fractures in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the prevalence of and risk factors for low bone mineral
      density (BMD) and vertebral fractures in patients with systemic lupus
      erythematosus (SLE). METHODS: We studied 107 SLE patients. Demographic and
      clinical data were collected, and radiographs of the thoracic and lumbar spine
      and BMD measurements by dual x-ray absorptiometry were performed. Vertebral
      deformities were scored according to the method of Genant et al: fractures were
      defined as a reduction of > or = 20% of the vertebral body height. Osteoporosis
      was defined as a T score less than -2.5 SD and osteopenia as a T score less than 
      1.0 SD in at least 1 region of measurement. RESULTS: Osteopenia was present in
      39% of the patients and osteoporosis in 4% (93% female; mean age 41.1 years). In
      multiple regression analysis, low BMD in the spine was associated with a low body
      mass index (BMI), postmenopausal status, and 25-hydroxyvitamin D deficiency. Low
      BMD in the hip was associated with low BMI and postmenopausal status. At least 1
      vertebral fracture was detected in 20% of the patients. Vertebral fractures were
      associated with ever use of intravenous methylprednisolone and male sex.
      CONCLUSION: Risk factors for low BMD in SLE patients are low BMI, postmenopausal
      status, and vitamin D deficiency. While osteoporosis defined as a low T score was
      found in only 4% of the patients, osteoporotic vertebral fractures were detected
      in 20%. The high prevalence of low BMD and vertebral fractures implies that more
      attention must be paid to the prevention and treatment of osteoporosis and
      fractures in SLE.

PMID- 15986346
TI  - Frequency of osteopenia in children and young adults with childhood-onset
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the frequency of osteopenia in patients with childhood
      onset systemic lupus erythematosus (SLE) compared with that in healthy matched
      controls, and to evaluate the relationship between disease-related variables and
      bone mineral mass. METHODS: Bone mineral density (BMD) and bone mineral content
      (BMC) were measured in a cohort of 70 patients with childhood-onset SLE (mean +/-
      SD disease duration 10.8 +/- 8.3 years, mean +/- SD age 26.4 +/- 9.9 years) and
      70 age- and sex-matched healthy controls. BMD and BMC of the femoral neck, lumbar
      spine, total body, and distal one-third of the radius were measured by dual x-ray
      absorptiometry. We investigated the relationship between BMC and the following
      disease variables: cumulative dose of corticosteroids, organ damage, current use
      of corticosteroids, use of cyclophosphamide, age at disease onset, and disease
      activity at the time of diagnosis. Biochemical markers of bone metabolism were
      also measured. RESULTS: BMD values for the lumbar spine and femoral neck were
      significantly lower in patients than in healthy controls. The reduction in BMD of
      the lumbar spine was significantly greater than that of the total body. In
      multiple linear regression analyses, a higher cumulative corticosteroid dose was
      significantly associated with lower BMC of the lumbar spine and femoral neck.
      Decreased lumbar spine BMC was also related to male sex. CONCLUSION: The
      frequency of osteopenia was higher in patients with childhood-onset SLE than in
      matched controls. The lumbar spine was the most seriously affected skeletal site,
      followed by the femoral neck. The cumulative dose of corticosteroids was shown to
      be an important explanatory variable for BMC values in the lumbar spine and
      femoral neck.

PMID- 15986347
TI  - Angiography-negative primary central nervous system vasculitis in children: a
      newly recognized inflammatory central nervous system disease.
AB  - Inflammatory central nervous system (CNS) diseases in childhood comprise a wide
      spectrum of heterogeneous conditions. We studied 4 children with primary CNS
      vasculitis in whom results of magnetic resonance imaging studies were abnormal
      but results of conventional angiography were normal. We determined that
      angiography-negative, biopsy-confirmed primary small-vessel CNS vasculitis is a
      previously unrecognized distinct disease entity in children. The diagnosis must
      be considered in a child with a progressive, acquired diffuse or focal neurologic
      deficit, even if the results of conventional angiography are normal. A lesional
      brain biopsy is required to confirm the diagnosis. Use of immunosuppressive
      therapy plus aspirin leads to an excellent neurologic outcome.

PMID- 15986348
TI  - Damage caused by Wegener's granulomatosis and its treatment: prospective data
      from the Wegener's Granulomatosis Etanercept Trial (WGET).
AB  - OBJECTIVE: To analyze damage occurring in patients with Wegener's granulomatosis
      (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with
      disease activity, adverse events, and quality of life. METHODS: The Vasculitis
      Damage Index (VDI) was applied to all 180 patients at trial entry and every 6
      months throughout the trial. Items of damage were analyzed by presumed etiology
      (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's
      rank correlation coefficients were calculated between VDI scores and the
      Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares,
      number of adverse events, and the patients' quality-of-life assessments. RESULTS:
      The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the
      trial. This increase was due to damage that occurred despite (or because of)
      therapy, including visual impairment, hearing loss, nasal blockade, pulmonary
      fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal
      failure, and diabetes mellitus. Only 11% of the enrolled patients had not
      sustained a single VDI item after 1 year of enrollment. When adjusted for
      baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score
      at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated
      with the number of adverse events, particularly among patients with limited WG (P
      = 0.06). CONCLUSION: Damage from both active disease and its treatment remain
      important problems for patients with WG. Despite the dramatic improvements in
      patient survival achieved over the last several decades, only a few patients with
      WG emerge from a period of active disease without sustaining some damage from the
      disease itself, its treatment, or both. An important measure of future
      therapeutic approaches will be their ability to reduce the damage accrued over
      time.

PMID- 15986349
TI  - Infliximab, but not etanercept, induces IgM anti-double-stranded DNA
      autoantibodies as main antinuclear reactivity: biologic and clinical implications
      in autoimmune arthritis.
AB  - OBJECTIVE: To analyze the clinical and biologic correlates of autoantibody
      induction during longer-term tumor necrosis factor alpha (TNFalpha) blockade with
      either the monoclonal antibody infliximab or the soluble receptor etanercept.
      METHODS: Thirty-four patients with spondylarthropathy (SpA) and 59 patients with
      rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally,
      20 patients with SpA were treated with etanercept for 1 year. Sera were blindly
      analyzed for antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA)
      antibodies, anti-extractable nuclear antigen (anti-ENA) antibodies, and
      antihistone, anti-nucleosome, and anticardiolipin antibodies (aCL). The anti
      dsDNA antibodies were isotyped. RESULTS: High numbers of infliximab-treated
      patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively)
      and anti-dsDNA antibodies (70.6% and 49.2%, respectively) after 1 year, but no
      further increase between year 1 and year 2 was observed. In contrast, induction
      of ANAs and anti-dsDNA antibodies was observed only occasionally in the
      etanercept-treated patients with SpA (10% of patients each). Isotyping revealed
      almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which disappeared upon
      interruption of treatment. Neither infliximab nor etanercept induced other lupus
      related reactivities such as anti-ENA antibodies, antihistone antibodies, or anti
      nucleosome antibodies, and no clinically relevant lupus-like symptoms were
      observed. Similarly, infliximab but not etanercept selectively increased IgM but
      not IgG aCL titers. CONCLUSION: The prominent ANA and anti-dsDNA autoantibody
      response is not a pure class effect of TNFalpha blockers, is largely restricted
      to short-term IgM responses, and is not associated with other serologic or
      clinical signs of lupus. Similar findings with aCL suggest that modulation of
      humoral immunity may be a more general feature of infliximab treatment.

PMID- 15986350
TI  - Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced
      arthritis by a different mode of action from that of interleukin-1 receptor
      antagonist.
AB  - OBJECTIVE: To discern the mode of interleukin-1 (IL-1) inhibition of soluble IL-1
      receptor accessory protein (sIL-1RAcP) by comparison with IL-1 receptor
      antagonist (IL-1Ra) in arthritis. METHODS: Adenoviral vectors encoding either sIL
      1RAcP or IL-1Ra were administered systemically before onset of collagen-induced
      arthritis in DBA/1 mice. Anti-bovine type II collagen IgG and IL-6 were
      quantified in serum. Proliferative response of splenic T cells was determined in
      the presence of sIL-1RAcP or IL-1Ra. The effect on IL-1 inhibition of recombinant
      sIL-1RAcP and IL-1Ra was further examined in vitro, using NF-kappaB luciferase
      reporter cell lines. Quantitative polymerase chain reaction was used to determine
      the relative messenger RNA expression of the IL-1 receptors. RESULTS: Adenoviral
      overexpression of both sIL-1RAcP and IL-1Ra resulted in amelioration of the
      collagen-induced arthritis. Both IL-1 antagonists reduced the circulating levels
      of antigen-specific IgG2a antibodies, but only IL-1Ra was able to inhibit
      lymphocyte proliferation. By using purified lymphocyte populations derived from
      NF-kappaB reporter mice, we showed that sIL-1RAcP inhibits IL-1-induced NF-kappaB
      activity in B cells but not T cells, whereas IL-1Ra inhibited IL-1 on both cell
      types. A study in a panel of NF-kappaB luciferase reporter cells showed that the
      sIL-1RAcP inhibits IL-1 signaling on cells expressing either low levels of
      membrane IL-1RAcP or high levels of IL-1RII. CONCLUSION: We show that the sIL
      1RAcP ameliorated experimental arthritis without affecting T cell immunity, in
      contrast to IL-1Ra. Our results provide data in support of receptor competition
      by sIL-1RAcP as an explanation for the different mode of IL-1 antagonism in
      comparison with IL-1Ra.

PMID- 15986351
TI  - Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+
      regulatory T cells.
AB  - OBJECTIVE: Regulatory T cells play an important role in the prevention of
      autoimmunity and have been shown to be effective in the treatment of experimental
      colitis, a T cell-mediated and organ-specific disease. We previously demonstrated
      that intrinsic CD25+ regulatory T cells modulate the severity of collagen-induced
      arthritis (CIA), which, in contrast to colitis, is a systemic antibody-mediated
      disease and an accepted model of rheumatoid arthritis. We undertook this study to
      determine whether regulatory T cells have the potential to be used
      therapeutically in arthritis. METHODS: We transferred CD4+,CD25+ T cells into
      mice exhibiting arthritis symptoms, both immunocompetent mice and mice subjected
      to lethal irradiation and rescued with syngeneic bone marrow transplantation.
      RESULTS: A single transfer of regulatory T cells markedly slowed disease
      progression, which could not be attributed to losses of systemic type II collagen
      specific T and B cell responses, since these remained unchanged after adoptive
      transfer. However, regulatory T cells could be found in the inflamed synovium
      soon after transfer, indicating that regulation may occur locally in the joint.
      CONCLUSION: Our data indicate that CD25+ regulatory T cells can be used for the
      treatment of systemic, antibody-mediated autoimmune diseases, such as CIA.

PMID- 15986352
TI  - Association of the PTPN22 locus with rheumatoid arthritis in a New Zealand
      Caucasian cohort.

PMID- 15986353
TI  - Clinical images: Radiographic healing of osseous sarcoidosis.

PMID- 15986354
TI  - Increased levels of serum protein oxidation and correlation with disease activity
      in systemic lupus erythematosus.
AB  - OBJECTIVE: To examine protein oxidation in systemic lupus erythematosus (SLE) and
      to correlate levels of protein oxidation products with disease activity. METHODS:
      Serum was collected from SLE patients and healthy control subjects. Protein-bound
      carbonyls and the pro-oxidant enzyme myeloperoxidase (MPO) were quantified by
      enzyme-linked immunosorbent assay. Protein thiols were quantified using 5,5'
      dithionitrobenzoic acid. Protein-bound amino acids and methionine, tyrosine, and
      phenylalanine oxidation products were quantified by acid hydrolysis and high
      performance liquid chromatography. Disease activity was assessed by the Systemic
      Lupus Erythematosus Disease Activity Index (SLEDAI). Levels of anti-double
      stranded DNA (anti-dsDNA) antibodies were measured by radioimmunoassay. RESULTS:
      Compared with control subjects, SLE patients exhibited elevated levels of protein
      carbonyls (0.108 +/- 0.078 versus 0.064 +/- 0.028 nmoles/mg of protein; P =
      0.046), decreased levels of protein thiols (3.9 +/- 1.1 versus 4.9 +/- 0.7
      nmoles/mg of protein; P = 0.003), decreased levels of protein-bound methionine (P
      = 0.0007), and increased levels of protein-bound methionine sulfoxide (P =
      0.0043) and 3-nitrotyrosine (P = 0.0477). SLE patients with high SLEDAI scores or
      elevated anti-dsDNA antibody levels exhibited increased oxidation compared with
      patients with low SLEDAI scores or low antibody levels. Serum MPO levels were
      decreased in SLE patients (P = 0.03), suggesting that this enzyme is not
      responsible for the enhanced protein oxidation. CONCLUSION: We found elevated
      levels of multiple markers of protein oxidation in sera from SLE patients
      compared with controls, and these levels correlated with disease activity. The
      findings suggest that protein oxidation may play a role in the pathogenesis of
      chronic organ damage in SLE.

PMID- 15986355
TI  - NF-kappaB protects Behcet's disease T cells against CD95-induced apoptosis up
      regulating antiapoptotic proteins.
AB  - OBJECTIVE: To determine whether prolongation of the inflammatory reaction in
      patients with Behcet's disease (BD) is related to apoptosis resistance and is
      associated with the up-regulation of antiapoptotic factors. METHODS: The
      percentage of cell death was evaluated by flow cytometry in peripheral blood
      mononuclear cells from 35 patients with BD and 30 healthy volunteers. The
      expression levels of antiapoptotic factors and NF-kappaB regulatory proteins were
      measured using Western blotting and immunohistochemical analyses. To down
      regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro
      to thalidomide and subjected to transfection with NF-kappaB small interfering
      RNA. RESULTS: Although CD95 is highly expressed in BD T cells, the absence of
      sensitivity to CD95-induced apoptosis observed may be attributable to the
      inhibitory action of antiapoptotic genes. Immunoblot analysis for major
      antiapoptotic proteins showed considerable up-regulation of the short form of
      cellular FLIP (cFLIP) and Bcl-x(L) in BD activated T cells, while levels of Bcl
      2, caspase 3, and caspase 8 in activated T cells from patients with BD were
      comparable with those in activated T cells from normal donors. Moreover,
      expression of IKK and IkappaB was up-regulated, whereas NF-kappaB translocated to
      the nucleus in BD T cells, suggesting that NF-kappaB activation may modulate the
      expression of antiapoptotic genes. Interestingly, thalidomide and NF-kappaB small
      interfering RNA down-regulated cFLIP and Bcl-x(L) expression levels and
      sensitized BD activated T cells to CD95-induced apoptosis. CONCLUSION: Taken
      together, these results indicate that NF-kappaB contributes to the regulation of
      the apoptosis-related factors and death receptors leading to apoptosis resistance
      in BD T cell subsets. Our results suggest that NF-kappaB plays a crucial role in
      the pathogenesis of BD, and that its pharmacologic control could represent a key
      strategy in modulating specific immune-mediated disease.

PMID- 15986356
TI  - Successful treatment of refractory Schnitzler syndrome with anakinra: comment on
      the article by Hawkins et al.

PMID- 15986357
TI  - BAFF overexpression and accelerated glomerular disease in mice with an incomplete
      genetic predisposition to systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether overexpression of BAFF can accelerate the
      development of systemic lupus erythematosus-associated end-organ disease in hosts
      with an underlying autoimmune diathesis. METHODS: We introduced a BAFF transgene
      (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for
      serologic autoimmunity and renal pathology. RESULTS: B6.Sle1.BAFF and
      B6.Nba2.BAFF mice, but not non-Tg littermates, frequently developed severe
      glomerular pathology by 3 months of age. Age-matched B6.BAFF mice, despite renal
      Ig deposits and increases in B cells and Ig production similar to those in
      B6.Sle1.BAFF and B6.Nba2.BAFF mice, did not develop glomerular pathology. In
      B6.Sle1.BAFF and B6.Nba2.BAFF mice, severity of glomerular disease did not
      obligately correlate with circulating levels of IgG anti-chromatin and/or anti
      double-stranded DNA antibodies or with amounts of these autoantibodies deposited
      in the kidneys. Even in mice with severe glomerular disease, renal
      tubulointerstitial infiltrates were very limited, and increased proteinuria was
      not detected. CONCLUSION: BAFF-driven effects on glomerular pathology may be
      mediated, at least in part, by autoantibodies with specificities other than
      chromatin and/or by autoantibody-independent means. There is an uncoupling of
      BAFF-driven precocious glomerular pathology from concomitant development of
      clinically apparent renal disease, strongly suggesting that BAFF overexpression
      works in concert with other factors to promote overt renal disease.

PMID- 15986358
TI  - Weight loss reduces knee-joint loads in overweight and obese older adults with
      knee osteoarthritis.
AB  - OBJECTIVE: To determine the relationship between change in body mass and knee
      joint moments and forces during walking in overweight and obese older adults with
      knee osteoarthritis (OA) following an 18-month clinical trial of diet and
      exercise. METHODS: Data were obtained from 142 sedentary, overweight, and obese
      older adults with self-reported disability and radiographic evidence of knee OA
      who underwent 3-dimensional gait analysis. Gait kinetic outcome variables
      included peak knee-joint forces and peak internal knee-joint moments. Mixed
      regression models were created to predict followup kinetic values, using followup
      body mass as the primary explanatory variable. Baseline body mass was used as a
      covariate, and thus followup body mass was a surrogate measure for change in body
      mass (i.e., weight loss). RESULTS: There was a significant direct association
      between followup body mass and peak followup values of compressive force (P =
      0.001), resultant force (P = 0.002), abduction moment (P = 0.03), and medial
      rotation moment (P = 0.02). A weight reduction of 9.8 N (1 kg) was associated
      with reductions of 40.6 N and 38.7 N in compressive and resultant forces,
      respectively. Thus, each weight-loss unit was associated with an approximately 4
      unit reduction in knee-joint forces. In addition, a reduction in body weight of
      9.8 N (1 kg) was associated with a 1.4% reduction (0.496 Nm) in knee abduction
      moment. CONCLUSION: Our results indicate that each pound of weight lost will
      result in a 4-fold reduction in the load exerted on the knee per step during
      daily activities. Accumulated over thousands of steps per day, a reduction of
      this magnitude would appear to be clinically meaningful.

PMID- 15986359
TI  - Association of cartilage defects with loss of knee cartilage in healthy, middle
      age adults: a prospective study.
AB  - OBJECTIVE: The significance of asymptomatic knee cartilage defects in healthy
      individuals is not known. The aim of this study was to examine the association
      between cartilage defects in the knee and cartilage volume both cross-sectionally
      and longitudinally in healthy, middle-age adults. METHODS: Eighty-six healthy men
      and women (mean +/- SD age 53.8 +/- 8.8 years) underwent T1-weighted fat
      suppressed magnetic resonance imaging of their dominant knees at baseline and at
      the 2-year followup visit. Knee cartilage volume was measured. Cartilage defects
      were scored according to a grading system (0-4) and as present (a defect score of
      > or = 2) or absent in the medial and lateral tibiofemoral compartments. RESULTS:
      Cartilage defects in the medial and lateral tibiofemoral compartments were very
      common (in 61% and 43% of subjects, respectively). Those with cartilage defects
      had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral
      tibial cartilage volume, and a 19% reduction in total femoral cartilage volume
      relative to those with no cartilage defects in cross-sectional analyses (all P <
      0.05). In the medial tibiofemoral compartment, the annual loss of tibial
      cartilage in those with cartilage defects was 2.5% (95% confidence interval [95%
      CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI
      0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk
      factors for osteoarthritis (OA). CONCLUSION: These data suggest that the presence
      of asymptomatic, non-full-thickness medial tibiofemoral cartilage defects
      identifies healthy individuals most likely to lose knee cartilage in the absence
      of radiographic knee OA. Thus, interventions aimed at reducing or reversing
      cartilage defects may reduce the risk of subsequent knee OA.

PMID- 15986360
TI  - Requirement of activation of complement C3 and C5 for antiphospholipid antibody
      mediated thrombophilia.
AB  - OBJECTIVE: Antiphospholipid antibodies (aPL) have been shown to induce
      thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis
      of aPL-induced thrombosis, although not completely understood, may involve
      platelet and endothelial cell activation as well as procoagulant effects of aPL
      directly on clotting pathway components. Recent studies have shown that
      uncontrolled complement activation leads to fetal death in aPL-treated mice. In
      this study, we tested the hypothesis that aPL are responsible for activation of
      complement, thus generating split products that induce thrombosis. METHODS: To
      study thrombus dynamics and adhesion of leukocytes we used in vivo murine models
      of thrombosis and microcirculation, in which injections of aPL were used.
      RESULTS: Mice deficient in complement components C3 and C5 were resistant to the
      enhanced thrombosis and endothelial cell activation that was induced by aPL.
      Furthermore, inhibition of C5 activation using anti-C5 monoclonal antibodies
      prevented thrombophilia induced by aPL. CONCLUSION: These data show that
      complement activation mediates 2 important effectors of aPL, induction of
      thrombosis and activation of endothelial cells.

PMID- 15986361
TI  - Rapid modulation of inhibitory synaptic currents in cerebellar Purkinje cells by
      BDNF.
AB  - The present study examined the acute effects of exogenous BDNF on inhibitory
      synaptic currents in Purkinje cells in cerebellar cultures. Miniature inhibitory
      postsynaptic currents (mIPSCs) were recorded in cultures (20-30 days in vitro),
      using discontinuous single electrode voltage clamp (dSEVC) technique. The effects
      of BDNF were studied in untreated control cultures and in cultures in which the
      endogenous levels of BDNF were decreased by chronic block of neural activity with
      tetrodotoxin (TTX). Chronic activity deprivation did not alter the amplitude of
      mIPSCs in Purkinje cells, and acute application of BDNF (50 ng/ml) to Purkinje
      cells in TTX-treated cultures significantly potentiated the amplitude and
      frequency of mIPSCs. By contrast, acute application of BDNF (50 ng/ml) produced
      no significant changes on mIPSC activity in control neurons. At higher
      concentrations of BDNF (100 ng/ml), comparable effects on mIPSC activity were
      also observed in control neurons. Preincubation of cerebellar cultures with
      K252a, an inhibitor of tyrosine kinases, effectively blocked the effects of BDNF
      on mIPSCs. These results indicate that functional inhibitory synapses develop in
      the absence of neural activity, and that activation of TrkB receptors by BDNF
      modulates inhibitory neurotransmission in Purkinje cells at both pre- and
      postsynaptic sites.

PMID- 15986362
TI  - Effects of corticotropin-releasing hormone receptor antagonists on cocaine
      induced dopamine overflow in the medial prefrontal cortex and nucleus accumbens
      of rats.
AB  - Recent evidence suggests an important role for corticotropin-releasing hormone
      (CRH) and CRH receptors in cocaine reinforcement. CRH receptor antagonists reduce
      cocaine self-administration and attenuate the reinstatement of extinguished
      cocaine-seeking behavior, but little is known about the mechanisms involved. One
      possible mechanism for these effects may involve the cocaine-induced activation
      of CRH located in brain regions outside of the hypothalamus. CRH has been shown
      to increase dopaminergic transmission in regions relevant for cocaine
      reinforcement, such as the medial prefrontal cortex and the nucleus accumbens.
      Here, we report that CP-154,526, a CRH1-receptor antagonist, actually enhances
      cocaine-induced increases in dopamine overflow in the medial prefrontal cortex,
      measured using in vivo microdialysis. In contrast, the receptor antagonist did
      not alter cocaine-induced increases in dopamine in most of the nucleus accumbens,
      except for the most rostral part. These data suggest a surprising role for
      prefrontal cortex dopamine in the ability of CRH-receptor antagonists to
      attenuate cocaine seeking in rats.

PMID- 15986363
TI  - A transient expression of functional alpha2-adrenergic receptors in white matter
      of the developing brain.
AB  - Norepinephrine is a neurotransmitter with peripheral and central actions mediated
      by alpha-1, alpha-2, and beta-adrenergic receptors. In this paper, we report an
      expression of alpha-2 adrenergic receptors in developing white matter tracts as
      revealed by [(3)H]RX821002 autoradiography. In rats, these receptors are present
      in the corpus callosum and anterior commissure at gestational day 20.
      Quantification of their postnatal expression reveals peak expression in the
      corpus callosum at postnatal day 1, which decreases with maturation and
      disappears by postnatal day 21. Expression in the anterior commissure is
      persistently elevated throughout the first ten days of postnatal development and
      then decreases to near background levels by postnatal day 21. Further
      characterization of the receptors by agonist-stimulated [(35)S]GTPgammaS binding
      verifies alpha-2 adrenergic receptors are functionally coupled to G proteins
      early in development and therefore are mature receptors. In situ hybridization
      did not detect mRNA for any of the alpha-2 adrenergic receptor subtypes (A, B,
      and C) in white matter tracts of postnatal day 5 brain. [(3)H]RX821002 emulsion
      autoradiography demonstrated autoradiographic grains that were of comparable
      density between cells and over cell bodies. Collectively, these data suggest that
      alpha-2 adrenergic receptors in neonatal commissures are synthesized at sites
      distant from their white matter expression and may be guiding the maturation of
      these brain commissures.

PMID- 15986364
TI  - The immunocytochemical localization of substance P in the human striatum: a
      postmortem ultrastructural study.
AB  - The striatum is a basal ganglia structure that is involved in motor, cognitive,
      and behavioral functions. In the striatum, the neuroactive peptide, substance P,
      is colocalized with GABA in the subset of medium spiny neurons that projects to
      the substantia nigra. Normal human striata (n = 5) obtained from the Maryland
      Brain Collection were processed for substance P immunoreactivity, prepared for
      electron microscopy, and analyzed using both stereology and simple profile
      counts. Most substance P-labeled neurons had a nonindented nucleus and a moderate
      amount of cytoplasm, typical of medium spiny projection neurons in other species.
      A small percentage (8%) of labeled neurons had indented nuclei, but otherwise had
      similar morphology. Synapses formed on labeled cell bodies were rare. Synapses
      formed by substance P-labeled axon terminals constituted 4.4% of the total
      synapses in the neuropil. Labeled terminals (1) formed synapses with both spines
      and dendrites with approximately equal frequency, (2) formed mostly symmetric
      synapses (76-85%), and (3) formed synapses predominantly with unlabeled (78%)
      profiles. Substance P-labeled spines varied in shape and comprised 37-42% of all
      spines forming synapses. In the caudate, the proportion of synapses with
      perforated postsynaptic densities was 55% on unlabeled vs. 45% on labeled spines,
      but in the putamen, this type of synapse was much more frequently present on
      unlabeled (73%) vs. labeled (27%) spines. These data describe substance P in the
      normal human striatum, which serve as comparative data to that of other species
      as well as normative data for further studies of brain disease that may involve
      striatal substance P neurons.

PMID- 15986365
TI  - Selective cyclooxygenase 2 inhibitors and cardiovascular events.

PMID- 15986366
TI  - Anti-tumor necrosis factor alpha blockade in the treatment of juvenile
      spondylarthropathy.
AB  - OBJECTIVE: Persistent inflammation refractory to standard antirheumatic therapy
      in children with juvenile spondylarthropathy (SpA) leads to morbidity and reduced
      quality of life. Tumor necrosis factor alpha (TNFalpha) plays an important role
      in the pathogenesis of synovitis and enthesitis. This study was undertaken to
      examine the impact of anti-TNFalpha agents on juvenile SpA that is refractory to
      nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying antirheumatic
      drugs, and corticosteroids. METHODS: Ten juvenile SpA patients with a mean +/-
      SEM age of 15.0 +/- 0.7 years and disease duration of 4.4 +/- 0.8 years, all of
      whom were HLA-B27 positive, were followed up for 1 year after initiation of
      either infliximab (n = 8) or etanercept (n = 2). Outcomes examined were within
      subject differences in the tender entheseal count (TEC) and active joint count
      (AJC), markers of inflammation, functional assessments (Childhood Health
      Assessment Questionnaire [C-HAQ] score), and requirements for antirheumatic
      drugs. RESULTS: At baseline, all patients exhibited active arthritis and
      enthesitis that were resistant to NSAIDs (n = 10), methotrexate (n = 6),
      sulfasalazine (n = 8), corticosteroids (oral n = 6, intravenous pulse n = 3, and
      intraarticular n = 6), and bisphosphonates (n = 2). In 2 patients, sulfasalazine
      (n = 2), corticosteroids (n = 1), and bisphosphonates (n = 1) were stopped after
      initiation of the anti-TNFalpha agent. In all patients, the arthritis and
      enthesitis significantly improved as evidenced by remission of the TEC and AJC by
      6 months that was sustained during the 1-year followup, markers of inflammation
      and C-HAQ scores normalized, and there was a reduction in requirements for
      antirheumatic drugs (reduced dosage or discontinuation of NSAIDs n = 10,
      methotrexate n = 5, sulfasalazine n = 6, corticosteroids n = 4, and
      bisphosphonates n = 1). CONCLUSION: Anti-TNFalpha therapy is a potential novel
      treatment for refractory juvenile SpA. Further prospective studies are required
      to examine the effectiveness and long-term outcomes of anti-TNFalpha therapy in
      this cohort.

PMID- 15986367
TI  - Dysregulation of chemokine receptor expression and function by B cells of
      patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To assess whether abnormal chemokine receptor expression and/or
      abnormal responsiveness to the cognate ligands might underlie some of the
      disturbances in B cell homeostasis characteristic of primary Sjogren's syndrome
      (SS). METHODS: Chemokine receptor expression by CD27- naive and CD27+ memory B
      cells from patients with primary SS and healthy control subjects was analyzed
      using flow cytometry, single-cell reverse transcriptase-polymerase chain reaction
      (RT-PCR), and migration assays. RESULTS: In contrast to healthy subjects,
      significantly higher expression of both surface CXCR4 and CXCR4 messenger RNA
      (mRNA) was seen in peripheral blood B cells from patients with primary SS. These
      differences were most prominent in CD27- naive B cells (P < or = 0.0006). In
      addition, significantly higher frequencies of CD27- naive B cells from patients
      with primary SS expressed mRNA for the inhibitory regulator of G protein
      signaling 13 (P = 0.001). Expression of CXCR5 by peripheral CD27+ memory B cells
      was moderately diminished in patients with primary SS compared with healthy
      controls (P = 0.038). No significant differences were noted in the expression of
      CXCR3, CCR6, CCR7, and CCR9 between B cells from healthy controls and those from
      patients with primary SS. Transmigration assays of blood B cells from patients
      with primary SS and healthy controls showed comparable responses of CD27- naive B
      cells but significantly diminished responses of activated primary SS CD27+ memory
      B cells to the ligands of CXCR4 and CXCR5, CXCL12 (P = 0.032), and CXCL13 (B
      lymphocyte chemoattractant; B cell-attracting chemokine 1; P = 0.018),
      respectively, when compared with those from healthy controls. Finally, compared
      with controls, peripheral reduction but glandular accumulation of
      CXCR4+,CXCR5+,CD27+ memory B cells was identified in patients with primary SS.
      CONCLUSION: In primary SS, overexpression of CXCR4 by circulating blood B cells
      does not translate into enhanced migratory response to the cognate ligand,
      CXCL12. This migratory response may be modulated by intracellular regulators.
      Retention of CXCR4+,CXCR5+, CD27+ memory B cells in the inflamed glands seems to
      contribute to diminished peripheral CD27+ memory B cells in primary SS.

PMID- 15986368
TI  - Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during
      necrotic cell death.
AB  - OBJECTIVE: Autoantibodies to DNA topoisomerase I (topo I) are associated with
      diffuse systemic sclerosis (SSc), appear to be antigen driven, and may be
      triggered by cryptic epitopes exposed during in vivo topo I fragmentation. These
      autoantibodies recognize topo I and fragments of this autoantigen generated
      during apoptosis and necrosis. We undertook this study to determine whether
      lysosomal cathepsins are involved in topo I fragmentation during necrosis.
      METHODS: Topo I cleavage during necrosis was assessed by immunoblotting of
      lysates from L929 fibroblasts exposed to tumor necrosis factor alpha (TNFalpha)
      and the broad caspase inhibitor Z-VAD-FMK, and by immunoblotting of lysates from
      endothelial cells treated with HgCl2. Purified topo I and L929 nuclei were
      incubated with cathepsins B, D, G, H, and L, and topo I cleavage was detected by
      immunoblotting. The intracellular localization of cathepsin L activity and topo I
      in necrotic cells was examined using fluorescence microscopy. RESULTS: Treatment
      of L929 cells with TNFalpha and Z-VAD-FMK induced caspase-independent cell death
      with necrotic morphology. This cell death involved topo I cleavage into fragments
      of approximately 70 kd and 45 kd. This cleavage profile was reproduced in vitro
      by cathepsins L and H and was inhibited by the cathepsin L inhibitor Z-FY-CHO.
      During necrosis, cathepsin L activity diffused from lysosomes into the cytoplasm
      and nucleus, whereas topo I partially relocalized to the cytoplasm. Z-FY-CHO
      delayed necrosis and partially blocked topo I cleavage. The topo I cleavage
      fragments were also detected in necrotic endothelial cells and recognized by SSc
      sera containing anti-topo I antibodies. CONCLUSION: These results implicate
      cathepsins, particularly cathepsin L, in the cleavage of topo I during necrosis.
      This cleavage may generate potentially immunogenic fragments that could trigger
      anti-topo I immune responses in SSc.

PMID- 15986369
TI  - Disease modification in osteoarthritis: are drugs the answer?

PMID- 15986370
TI  - Risk and case characteristics of tuberculosis in rheumatoid arthritis associated
      with tumor necrosis factor antagonists in Sweden.
AB  - OBJECTIVE: Because treatment with tumor necrosis factor (TNF) antagonists may
      increase the risk of tuberculosis (TB), and because knowledge of the risk of TB
      in rheumatoid arthritis (RA) not treated with biologics is scarce and of
      uncertain generalizability to low-risk populations, this study sought to
      determine the risk of TB among Swedish patients with RA. METHODS: Using data from
      Swedish nationwide and population-based registers and data from an ongoing
      monitoring program of TNF antagonists, the relative risks of TB in patients with
      RA (versus the general population) and of TB associated with TNF antagonists
      (versus RA patients not treated with biologics) were determined by comparing the
      incidence of hospitalization for TB in 3 RA cohorts and 2 general population
      cohorts from 1999 to 2001. We also reviewed the characteristics of all reported
      cases of TB in RA patients treated with TNF antagonists in Sweden and calculated
      the incidence of TB per type of TNF antagonist between 1999 and 2004. RESULTS:
      During 1999-2001, RA patients who were not treated with TNF antagonists were at
      increased risk of TB versus the general population (relative risk 2.0, 95%
      confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists
      had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA
      patients not treated with TNF antagonists. The reported TB cases during 1999-2004
      in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both)
      were predominantly pulmonary. TB occurred up to 3 years following the start of
      treatment. CONCLUSION: Irrespective of whether TNF antagonists are administered,
      Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF
      antagonists were associated with an increased risk of TB, up to 4-fold in
      magnitude. This increased risk may persist over time during treatment and is
      related to both infliximab and etanercept.

PMID- 15986371
TI  - Intracellular free radical production in synovial T lymphocytes from patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the cellular and molecular sources of oxidative stress
      in patients with rheumatoid arthritis (RA) through analysis of the production of
      reactive oxygen species (ROS) in synovium. METHODS: Cytochemical procedures based
      on the 3,3'-diaminobenzidine (DAB)-Mn2+ deposition technique were used on unfixed
      cryostat sections of synovium from RA patients and rheumatic disease controls.
      For immunophenotyping, sections were incubated, fixed, and stained with
      fluorescein isothiocyanate-labeled antibodies. Fluorescence-activated cell sorter
      analysis of the ROS-reactive dye 6-carboxy-2',7'-dichlorodihydrofluorescein
      diacetate-di(acetoxymethyl ester) was used to measure intracellular ROS in T
      lymphocytes from peripheral blood and synovial fluid. To determine which enzymes
      produced ROS, different inhibitors were tested. RESULTS: Large quantities of DAB
      precipitated in the majority of RA synovial T lymphocytes, indicative of
      intracellular ROS production. These ROS-producing T lymphocytes were observed
      throughout the synovium. Polymerization of DAB was observed to a lesser extent in
      other forms of chronic arthritis, but was absent in osteoarthritis. DAB staining
      of cytospin preparations of purified RA synovial fluid T cells confirmed the
      presence of ROS-producing cells. One of the ROS involved appeared to be H2O2,
      since catalase suppressed intracellular ROS production. Superoxide dismutase,
      which uses superoxide as a substrate to form H2O2, diphenyleneiodonium (an
      inhibitor of NADPH oxidase), N(G)-monomethyl-L-arginine (an inhibitor of nitric
      oxide synthesis), nordihydroguaiaretic acid (an inhibitor of lipoxygenase), and
      rotenone (an inhibitor of mitochondrial ROS production) failed to suppress ROS
      production. CONCLUSION: Our findings show that chronic oxidative stress observed
      in synovial T lymphocytes is not secondary to exposure to environmental free
      radicals, but originates from intracellularly produced ROS. Additionally, our
      data suggest that one of the intracellularly generated ROS is H2O2, although the
      oxidase(s) involved in its generation remains to be determined.

PMID- 15986372
TI  - Development and validation of a clinical index for assessment of long-term damage
      in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To develop and validate a clinical measure of articular and
      extraarticular damage in patients with juvenile idiopathic arthritis (JIA).
      METHODS: The Juvenile Arthritis Damage Index (JADI), which is derived from
      physical examination and a brief review of the patient's clinical history, is
      composed of 2 parts: assessments of articular damage (JADI-A) and extraarticular
      damage (JADI-E). Instrument validation was accomplished by evaluating 158 JIA
      patients with disease duration of at least 5 years, seen consecutively over 21
      months. The instrument's feasibility, face and content validity, construct and
      discriminative ability, internal consistency, and interrater reliability were
      examined. RESULTS: Among the 158 JIA patients, 47% and 37% had articular and
      extraarticular damage, respectively. The JADI was found to be feasible and to
      possess both face and content validity. The JADI-A score correlated highly with
      the number of joints with limited range of motion (Spearman's r [r(S)] = 0.72)
      and correlated moderately with the Childhood Health Assessment Questionnaire
      score (r(S) = 0.41), Steinbrocker functional classification (r(S) = 0.50), and
      Poznanski's score of radiographic damage (r(S) = -0.54), thereby demonstrating
      good construct validity. Correlations with the JADI-E score were lower, owing to
      the heterogeneity of its items. The JADI-A discriminated well among different
      levels of disability. The internal consistency (Chronbach's alpha) of the JADI-A
      and JADI-E was 0.93 and 0.59, respectively. The intraclass correlation
      coefficients between pairs of independent observers ranged from 0.85 to 0.97.
      CONCLUSION: The JADI exhibited good reliability, construct validity, and
      discriminative ability and is therefore a valid instrument for the assessment of
      long-term damage in patients with JIA, in the context of both clinical management
      and research settings.

PMID- 15986374
TI  - Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid
      arthritis, but not Crohn's disease, in Canadian populations.
AB  - OBJECTIVE: A single-nucleotide polymorphism in the PTPN22 gene encoding the
      lymphoid protein tyrosine phosphatase (Lyp) has recently been identified as a
      functional variant associated with susceptibility to rheumatoid arthritis (RA),
      type 1 diabetes, and systemic lupus erythematosus. To determine whether
      association of this variant (PTPN22 1858T) with RA is reproducible and is also
      observed in another autoimmune condition, Crohn's disease, we investigated the
      association between the PTPN22 1858T allele and RA and Crohn's disease in a
      Canadian population. METHODS: Two RA case-control cohorts representing a total of
      1,234 patients and 791 healthy controls as well as a cohort of 455 patients with
      Crohn's disease and 190 controls were genotyped for the PTPN22 C1858T
      polymorphism, and genotype frequencies were compared between patients and
      controls. RESULTS: Significant association of the PTPN22 1858T allele with RA was
      detected in both the Toronto-based RA cohort (P = 1.6 x 10(-6), odds ratio [OR]
      1.8) and the Halifax-based RA cohort (P = 9.4 x 10(-4), OR 1.94). Association of
      the risk allele with RA was not affected by sex, age at disease onset, or the
      presence of either rheumatoid factor or rheumatoid nodules. No association
      between the PTPN22 risk allele and Crohn's disease was detected. CONCLUSION:
      These observations confirm the association of RA susceptibility with the PTPN22
      1858T allele. However, the data also reveal a lack of association between this
      variant and Crohn's disease, suggesting that the PTPN22 1858T allele is a risk
      allele for multiple, but not all, autoimmune diseases.

PMID- 15986373
TI  - Tumor necrosis factor alpha blockade treatment down-modulates the increased
      systemic and local expression of Toll-like receptor 2 and Toll-like receptor 4 in
      spondylarthropathy.
AB  - OBJECTIVE: Abnormal host defense against pathogens has been implicated in the
      pathogenesis of spondylarthropathy (SpA), a disease characterized by abundant
      synovial infiltration with innate immune cells. Given the role of Toll-like
      receptors (TLRs) in activation of innate inflammation and the occurrence of TLR
      dependent infections after tumor necrosis factor alpha (TNFalpha) blockade
      treatment, the present study was undertaken to analyze TLRs and their modulation
      by TNFalpha blockade in SpA. METHODS: Peripheral blood mononuclear cells (PBMCs)
      were obtained from SpA and rheumatoid arthritis (RA) patients during infliximab
      therapy, and from healthy controls. TLR-2 and TLR-4 expression and TNFalpha
      production upon lipopolysaccharide (LPS) stimulation were analyzed by flow
      cytometry on different monocyte subsets. Synovial biopsy specimens from 23 SpA
      patients before and after infliximab or etanercept treatment, from 15 RA
      patients, and from 18 osteoarthritis (OA) patients were analyzed by
      immunohistochemistry. RESULTS: Expression of TLR-4, but not TLR-2, was increased
      on PBMCs from patients with SpA, whereas both TLRs were increased in RA patients.
      TLR expression was particularly increased on the CD163+ macrophage subset.
      Infliximab reduced TLR-2 and TLR-4 expression on monocytes of SpA and RA
      patients, leading to lower levels than in controls and to impaired TNFalpha
      production upon LPS stimulation. In inflamed synovium, the expression of both
      TLRs and of CD163 was significantly higher in patients with SpA than in those
      with RA or OA. Paralleling the systemic effect, TLRs in synovium were down
      regulated following treatment with infliximab as well as etanercept, indicating a
      class effect of TNFalpha blockers. CONCLUSION: Inflammation in SpA is
      characterized by increased TLR-2 and TLR-4 expression, which is sharply reduced
      by TNFalpha blockade. These findings suggest a potential role of innate immunity
      mediated inflammation in SpA and provide an additional clue regarding the
      mechanism of action as well as the potential side effects of TNFalpha blockade.

PMID- 15986375
TI  - Retroviral gene transfer of an antisense construct against membrane type 1 matrix
      metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial
      fibroblasts.
AB  - OBJECTIVE: Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed
      prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the
      specific contribution of MT1-MMP to fibroblast-mediated destruction of articular
      cartilage is incompletely understood. This study used gene transfer of an
      antisense expression construct to assess the effects of MT1-MMP inhibition on the
      invasiveness of RASFs. METHODS: Retroviral gene transfer of a pLXIN vector-based
      antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably
      transduce RASFs. Levels of MT1-MMP RNA and protein were determined by
      quantitative polymerase chain reaction, Western blotting, and immunocytochemistry
      in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring
      for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were
      analyzed in the SCID mouse co-implantation model of RA. RESULTS: MT1-MMPalphaS
      transduced RASFs produced high levels of antisense RNA that exceeded endogenous
      levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of
      MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for
      60 days and significantly reduced the invasiveness of RASFs in the SCID mouse
      model. Whereas prominent invasion into cartilage by non-transduced and mock
      transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively),
      MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion
      score 1.8; P < 0.05). CONCLUSION: The data demonstrate that an antisense RNA
      expression construct against MT1-MMP can be generated and expressed in RASFs for
      at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage
      degradation by RASFs.

PMID- 15986376
TI  - Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking,
      older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk
      factors for the occurrence of venous thrombosis in lupus patients.
AB  - OBJECTIVE: Venous thrombosis is a relatively frequent and serious complication in
      systemic lupus erythematosus (SLE) that has been associated with the presence of
      antiphospholipid antibodies (aPL). However, venous thrombotic events can also be
      seen in patients without aPL, and only a few patients with aPL develop venous
      thrombosis. This study was carried out to ascertain other factors contributing to
      the development of venous thrombosis in SLE. METHODS: Patients with SLE, ages >
      or = 16 years with < or = 5 years disease duration and of Hispanic, African
      American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus
      nurture), a multiethnic, longitudinal study of outcome, were studied. Selected
      socioeconomic/demographic, clinical, laboratory, and treatment-exposure variables
      were compared between patients who developed and those who did not develop venous
      thrombotic events. Significant and clinically relevant variables were then
      entered into different multivariable models (Cox proportional hazards and
      unconditional stepwise logistic regression) to identify independent risk factors
      associated with the primary outcome. In another model, only patients who
      developed an event after enrollment (time 0) in the cohort were included.
      RESULTS: Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event
      after SLE diagnosis. In univariable analyses, smoking (P = 0.020), shorter
      disease duration at time 0 (P = 0.017), serum levels of total cholesterol, low
      density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus
      anticoagulant (LAC) (P = 0.045) were associated with venous thrombotic events.
      Survival analyses showed a time-dependent significant association of the primary
      outcome with smoking (P = 0.008) and a borderline significant association with
      the presence of LAC (P = 0.070). Multivariable models showed an independent
      association with smoking, age at time 0, disease activity over time, LAC, mean
      dose of glucocorticoids, and shorter disease duration at time 0. CONCLUSION:
      Venous thrombotic events occur early in the course of SLE. Our data confirm the
      association between LAC and venous thrombotic events. Smoking, shorter disease
      duration, older age, disease activity over time, and higher mean daily
      glucocorticoid dose were identified as additional risk factors for the
      development of this vascular complication. These findings may have implications
      for the management of patients with SLE.

PMID- 15986377
TI  - Characterization of the 5' regulatory region of the Drosophila Dmdop1 dopamine
      receptor-gene.
AB  - The pharmacological and functional properties of many biogenic-amine receptors
      have been thoroughly investigated. In contrast, knowledge about the
      transcriptional regulation of receptor genes is limited. Here we describe the
      structural and functional properties of the promoter region of a dopamine
      receptor-gene (Dmdop1) from Drosophila. The transcriptional start site was
      identified by 5'-RACE (5'-rapid amplification of cDNA ends) cloning and primer
      extension analysis. A consensus site for transcriptional initiation (INR element)
      is located 494 bp upstream of the ATG codon of the open reading-frame. The
      promoter neither contains TATA- nor CAAT boxes but several GC-rich elements.
      Relative promoter activity was monitored by CAT reporter-gene analysis in
      different neuronal cell lines. The Dmdop1 promoter contains one activating (
      454/+125) and two silencing regions (-1481/-454 and +125/+495). Interestingly,
      one silencing region harbours a CRE (cAMP responsive element) site. Since the
      DmDOP1 receptor leads to cAMP production in cells, the CRE site might contribute
      to the receptors' own expression by cAMP-dependent transcription factors.

PMID- 15986378
TI  - Intrahepatic gene expression profiles and alpha-smooth muscle actin patterns in
      hepatitis C virus induced fibrosis.
AB  - To gain insight into pathogenic mechanisms underlying fibrosis in hepatitis C
      virus (HCV)-mediated liver injury, we compared intrahepatic gene expression
      profiles in HCV-infected patients at different stages of fibrosis and alpha
      smooth muscle actin (alpha-SMA) staining patterns. We studied 21 liver biopsy
      specimens: 5 had no fibrosis (Ludwig-Batts stage 0); 10 had early portal or
      periportal fibrosis (stages 1 and 2); and 6, advanced fibrosis (stages 3 and 4).
      None of the patients had hepatocellular carcinoma. Transcriptional profiles were
      determined by high-density oligonucleotide microarrays. ANOVA identified 157
      genes for which transcript abundance was associated with fibrosis stage. These
      defined three distinct hierarchical clusters of patients. Patients with
      predominantly stage 0 fibrosis had increased abundance of mRNAs linked to
      glycolipid metabolism. PDGF, a potent stellate cell mitogen, was also increased.
      Transcripts with increased abundance in stages 1 and 2 fibrosis were associated
      with oxidative stress, apoptosis, inflammation, proliferation, and matrix
      degradation, whereas transcripts increased in stages 3 and 4 were associated with
      fibrogenesis and cellular proliferation. Cells staining for alpha-SMA were
      detectable at all stages but infrequent in advanced fibrosis without active
      inflammation. A high frequency of such cells was associated with mRNAs linked to
      glycolipid metabolism. In conclusion, the presence of alpha-SMA-positive HSCs and
      expression of PDGF in stage 0 fibrosis suggests that stellate cells are activated
      early in HCV-mediated injury, possibly in response to oxidative stress resulting
      from inflammation and lipid metabolism. Increased abundance of transcripts linked
      to cellular proliferation in advanced fibrosis is consistent with a
      predisposition to cancer. Supplementary material for this article can be found on
      the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270
      9139/suppmat/index/html).

PMID- 15986379
TI  - Responses of the silkworm tyramine receptor to 2-phenylethylamines and 5
      phenyloxazoles.
AB  - Tyramine (TA), a biogenic amine, attenuates intracellular cAMP production by
      acting on its receptor in insects. Several non-biogenic amines were examined for
      their actions on native and heterologously expressed silkworm TA receptors. 5-(4
      Hydroxyphenyl)oxazole, which showed an attenuating effect on cAMP production in
      silkworm-head membranes, did not attenuate forskolin-stimulated cAMP production
      in HEK-293 cells expressing the silkworm TA receptor, although the compound bound
      to the cloned receptor. 2-Phenylethylamines (2-PEAs), which showed positive and
      negative effects on cAMP production in silkworm-head membranes, inhibited [3H]TA
      binding to the cloned TA receptor. 2-Chloro-2-(4-chlorophenyl)ethylamine was the
      most potent inhibitor of [3H]TA binding among the 2-PEAs tested, with an IC50 of
      30.4 nM. This compound acted as an antagonist and abolished TA-attenuation of
      forskolin-stimulated cAMP production in the cloned TA receptor. The discrepancy
      in the effects of the non-biogenic amines on the native and cloned TA receptors
      remains to be further examined. A newly synthesized 2-PEA, 2-chloro-2-(4
      hydroxyphenyl)ethylamine, attenuated forskolin-stimulated cAMP production in the
      cloned TA receptor, indicating that the para-hydroxy group is important for the
      agonist action.

PMID- 15986380
TI  - Molecular characterization of the ebony gene from the American cockroach,
      Periplaneta americana.
AB  - Biogenic amines are an important class of primary messengers in the central (CNS)
      and peripheral nervous systems and in peripheral organs. These substances
      regulate and modulate many physiological and behavioral processes. Various
      inactivation mechanisms for these substances exist to terminate biogenic amine
      mediated signal transduction. In vertebrates, the enzymes monoamine oxidase
      and/or catechol-O-methyl-transferase are involved in these processes. In insects,
      however, in which both enzymes are low in abundance or absent, biogenic amines
      are inactivated mainly by N-acetylation or O-sulphation. In Drosophila, beta
      alanyl conjugation mediated by the Ebony protein has recently been shown to be a
      novel and alternative pathway for biogenic amine inactivation. Here, we report
      the cloning of ebony cDNA (Peaebony) from a brain-specific cDNA library of the
      cockroach Periplaneta americana. The open reading frame encodes a protein of 860
      amino acid residues (PeaEbony). The PeaEbony polypeptide shares homology to Ebony
      sequences from Anopheles gambiae, Apis mellifera, and Drosophila melanogaster. In
      addition, PeaEbony exhibits sequence similarity to a family of microbial non
      ribosomal peptide synthetases. The mRNA encoding PeaEbony is highly expressed in
      the cockroach brain and to a lesser extent in the salivary glands. PeaEbony is,
      therefore, probably involved in the inactivation of various biogenic amines
      through beta-alanyl conjugation in the cockroach CNS. Since the salivary glands
      in Periplaneta are innervated by dopaminergic and serotonergic neurons, PeaEbony
      probably also biochemically modifies dopamine and serotonin in these acinar
      glands.

PMID- 15986381
TI  - Cellular actions of biogenic amines.

PMID- 15986382
TI  - Molecular biology of the invertebrate dopamine receptors.
AB  - Dopamine is found in the nervous systems of both vertebrates and invertebrates.
      However, the specific actions of dopamine depend on the dopamine receptor type
      that is expressed in the target cell. As in mammals, different subtypes of
      dopamine receptors have been cloned and characterized from invertebrates, and
      these receptor subtypes have different structural and functional properties.
      Understanding how these receptors respond to dopamine and in which cells each
      receptor type is expressed is key to our understanding of the role of dopamine
      signaling. Comparison of the amino acid sequences and experimentally determined
      functional properties suggest that there are at least three distinct types of
      dopamine receptors in invertebrates. This review focuses on invertebrate dopamine
      receptors for which the genes have been isolated and identified, and examines our
      current knowledge of the functional and structural properties of these receptors,
      and their pharmacology and expression.

PMID- 15986383
TI  - Isolation, cloning, and tissue expression of a putative octopamine/tyramine
      receptor from locust visceral muscle tissues.
AB  - Octopamine has been shown to play major roles in invertebrate nervous systems as
      a neurotransmitter, neuromodulator, and neurohormone. Tyramine is the biochemical
      precursor of octopamine and its neuromodulatory role is now being investigated
      and clarified in invertebrates, particularly in insects. Both octopamine and
      tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are
      believed to play important functions in the regulation of physiological processes
      in locust oviduct. Here we report the isolation, cloning, and tissue expression
      of a putative octopamine/tyramine receptor from the locust, Locusta migratoria.
      Degenerate oligonucleotides in PCR reactions were first used to obtain partial
      cDNA sequences and then these partial sequences were used in screens to obtain a
      full-length cDNA. The cloned cDNA is about 3.1 kb long and encodes a protein of
      484 amino acid residues with typical characteristics of GPCRs including seven
      transmembrane domains and many signature residues. The amino acid sequence of the
      cloned cDNA displays sequence similarities with known GPCRs, particularly
      octopamine/tyramine receptors. Screening of the locust genomic DNA library
      resulted in isolation of a genomic DNA with the same size as the cDNA, indicating
      that the gene is intron-less. RT-PCR and Northern blot analyses revealed the
      expression of the receptor mRNA in brain, ventral nerve cord, oviduct, and midgut
      tissues. Southern blot analyses using EcoRI and HindIII restriction endonucleases
      recognized at least two distinct gene bands.

PMID- 15986384
TI  - Molecular and pharmacological analysis of an octopamine receptor from American
      cockroach and fruit fly in response to plant essential oils.
AB  - Octopamine receptors from American cockroach, Periplaneta americana (Pa oa1), and
      fruit fly, Drosophila melanogaster (OAMB), were cloned and permanently expressed
      in HEK-293 cells, and found to activate adenylate cyclase activity and increase
      [Ca2+]i levels through G-protein coupled receptor signaling pathways. Sequencing
      information (GenBank accession number AY333178) and functional data of Pa oa1
      were recently published. Saturation binding analysis with 3H-yohimbine was
      performed with Pa oa(1) and OAMB expressed in COS-7 cells. The K(d) values were
      determined to be 28.4 and 43.0 nM, respectively. B(max) was determined to be 11.8
      and 8.04 pmol receptor/mg protein, respectively. Competitive binding data using
      cell membranes expressing either OAMB or Pa oa1 demonstrated significantly
      decreased binding activity in binding assays performed in the presence of plant
      essential oils, eugenol, cinnamic alcohol, and trans-anethole. Eugenol decreased
      cAMP level in HEK-293 cells expressing Pa oa1, but trans-anethole increased cAMP
      in HEK-293 cells expressing OAMB. All three chemicals increased [Ca2+]i level in
      both cell models. Toxicity data against fruit flies and American cockroaches
      demonstrated species differences in response to treatment with tested plant
      essential oils. The toxicity of tested chemicals against wild type and octopamine
      mutant (iav) fly strains suggested that an octopamine receptor mediates the
      toxicity of cinnamic alcohol, eugenol, trans-antehole, and 2-phenethyl propionate
      against fruit flies. Collectively, the data suggest a correlation between
      cellular changes induced by tested plant essential oils and their toxicity
      against fruit fly and American cockroach.

PMID- 15986385
TI  - A transporter for phenolamine uptake in the arthropod CNS.
AB  - Biogenic monoamines play central roles in the nervous control of physiological
      processes in both vertebrates and invertebrates, each using a suite of
      neurotransmitters tailored through evolution. Among the ancillary proteins
      necessary for the deployment of monoamine transmitters are membrane-bound
      transporters that enable the reuptake of synaptically released transmitters.
      Transporters responsible for monoamine uptake include a novel transporter
      discovered in a pest insect, the cabbage looper Trichoplusia ni, which has high
      affinity for the phenolamines octopamine and tyramine. Sequence analysis suggests
      that this transporter has no direct ortholog in the sequenced genomes of model
      invertebrates. We report here a preliminary investigation into the true extent of
      the distribution of this type of transporter using RT-PCR with a set of
      degenerate primers selective for monoamine transporters on cDNAs made from the
      nervous systems of a range of arthropods. PCR products encoding the N-terminal
      region of orthologs of this transporter were detected in a variety of insect
      orders, as well as in a crustacean, but were not found in representatives of
      either the Diptera or the Hymenoptera. Thus, although this transporter is widely
      expressed in invertebrates, there are various invertebrates that appear to have
      evolved alternate ways of recycling phenolamine neurotransmitters released at the
      nerve synapse.

PMID- 15986386
TI  - Possible health implications of thermally processed foods--COST Action 927.

PMID- 15986387
TI  - Development of a food frequency questionnaire module and databases for compounds
      in cooked and processed meats.
AB  - There is ample evidence from basic research and animal carcinogenicity studies
      that heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are
      mutagens and carcinogens. However, there was a paucity of human data due to a
      lack of appropriate investigative tools. We developed the first validated cooked
      meat module within a food frequency questionnaire (FFQ) in the United States of
      America and created databases to be used in conjunction with this FFQ to estimate
      intake of HCAs and benzo[a]pyrene, a marker of PAHs. It became clear that other
      aspects of meat may also contribute to carcinogenesis; in particular, we are
      pursuing two additional areas: processed meat and iron exposure in relation to
      cancer risk. To investigate these hypotheses, we have expanded the cooked meat
      module to include detailed information on processed meats and fish. In addition,
      we are developing two databases, one for total iron and heme iron in cooked meat
      and the other for nitrite, nitrate, and N-nitroso compounds in processed meats.
      In this report, we will outline the methods used to develop the meat
      questionnaires, the databases, a software package for generating the intake
      values, and the methods used to generate nutritional data from nationally
      representative samples.

PMID- 15986388
TI  - Bread crust melanoidins as potential prebiotic ingredients.
AB  - Melanoidins are the final products of the Maillard reaction. They are a
      heterogeneous mixture of compounds characterized by brown color and high
      molecular weight. The physiological properties of melanoidins have been widely
      investigated and there is a general consensus on their poor digestibility and
      bioavailability. In vitro studies on food melanoidins are in many cases limited
      by their poor water solubility. This problem was recently overcome for bread
      melanoidins using an enzymatic digestion procedure. Bread melanoidins are
      constituted by low-molecular-weight, colored compounds linked to the gluten
      polymer. In this work, melanoidins from different bread types were investigated
      for their potential prebiotic activity by a static batch culture. Results showed
      that anaerobic bacteria, particularly Bifidobacteria strains, are able to use
      bread melanoidins as carbon source. The bacterial growth is different for the
      various types of melanoidins samples indicating that starting materials and
      processing conditions have a strong influence on the prebiotic potential of bread
      melanoidins. In all cases the bacterial growth obtained using bread melanoidins
      is lower than that previously observed using melanoidins from other sources, such
      as coffee silverskin.

PMID- 15986391
TI  - Regional distribution and cellular localization of the ETS-domain transcription
      factor, FEV, mRNA in the human postmortem brain.
AB  - The ETS transcription factor Fifth Ewing Variant (FEV) mRNA, a homologue of the
      rodent Pet-1 gene that is exclusively expressed in serotonin-containing neurons
      and is a critical determinant of serotonin neuronal differentiation and
      development, was examined in human postmortem brain tissue using in situ
      hybridization histochemistry. Studies revealed that FEV mRNA is robustly and
      exclusively expressed in the major serotonin-containing cell groups of the dorsal
      and median raphe nuclei located in the midbrain and pons of the human brainstem.
      The localization of transcription factor, FEV, mRNA in serotonin-containing
      neurons of the human brain raises questions regarding the functional significance
      of this transcription factor in regulating serotonin-related genes and its
      potential role in psychiatric illness.

PMID- 15986392
TI  - A2A adenosine receptors are located on presynaptic motor nerve terminals in the
      mouse.
AB  - Extracellular adenosine is present at the mammalian neuromuscular junction (NMJ)
      by virtue of its release from activated nerve terminals and muscle fibers, and as
      a metabolite of adenosine tri-phosphate, which is coreleased with acetylcholine.
      Two activities for adenosine have been described: an inhibitory effect presumed
      to be modulated by the A1 receptor subtype, and a facilitatory effect mediated by
      the A2A receptor subtype. To date, only pharmacological evidence is available for
      these actions. We have used an antibody against the A2A receptor subtype, and
      demonstrated that A2A receptors are present on presynaptic motor nerve terminals
      at NMJs but not on associated glial or muscle cells, in the mouse. These results
      therefore provide additional evidence that there are multiple adenosine receptors
      present at the NMJ, and that stimulation of quantal and nonquantal release of
      acetylcholine (ACh) could be mediated by A2A receptors.

PMID- 15986393
TI  - P2Y1 receptors inhibit both strength and plasticity of glutamatergic synaptic
      neurotransmission in the rat prefrontal cortex.

PMID- 15986394
TI  - The prevalence of undiagnosed pulmonary arterial hypertension in subjects with
      connective tissue disease at the secondary health care level of community-based
      rheumatologists (the UNCOVER study).
AB  - OBJECTIVE: Most of the data about the prevalence of pulmonary arterial
      hypertension (PAH) are from tertiary centers that are biased toward seeing more
      severe cases; therefore, the true prevalence of PAH among patients with
      connective tissue disease is unknown. We sought to determine the point prevalence
      of undiagnosed PAH in community-based rheumatology practices. METHODS: The study
      design was a multicenter, prospective and retrospective survey and analysis of
      clinical cases in 50 community rheumatology practices. We evaluated a total of
      909 patients with either scleroderma (systemic sclerosis [SSc]) or mixed
      connective tissue disease (MCTD). If a subject had not been diagnosed as having
      PAH, then a new Doppler echocardiogram was obtained to measure cardiac
      parameters, including estimated right ventricular systolic pressure (ERVSP), and
      a full review of medical records was done. RESULTS: Of 909 screened patients, 791
      were evaluable and completed the study; 669 had not previously been studied for
      PAH. Of these 669 patients, 89 (13.3%) were found by Doppler echocardiography to
      have an ERVSP of > or = 40 mm Hg. Of these 89 patients, 82 (92.1%) had SSc and 7
      (7.9%) had MCTD. The total prevalence of PAH in the survey was 26.7% (211 of 791
      patients, including 122 with known PAH and 89 newly diagnosed as having PAH).
      Doppler echocardiographic data showed 20 of 89 patients (22.5%) with ERVSP of >
      or = 50 mm Hg, 20 of 89 patients (22.5%) with increased RV dimension, and 25 of
      89 patients (28.1%) with right atrial enlargement. Patients with ERVSP > or = 40
      mm Hg had decreased exercise tolerance compared with those with ERVSP <40 mm Hg
      (27% compared with 9.5%, respectively, were severely symptomatic). CONCLUSION: A
      significant number of patients with SSc or MCTD (13.3%) followed up in a
      community rheumatology practice setting have undiagnosed elevated ERVSP
      consistent with PAH.

PMID- 15986395
TI  - Papillary carcinoma of the thyroid <or=1.0 cm: rarely incidental or occult any
      more.
AB  - BACKGROUND: Papillary carcinomas of the thyroid that measure <or=1.0 cm often are
      termed incidental or occult tumors. In the current study, the author sought to
      determine the incidence of such tumors at his institution over a relatively short
      period. METHODS: The author reviewed the results from all patients who underwent
      thyroid resection over a 65-month period and correlated the findings with
      clinical and cytologic information. RESULTS: During the study period, a total of
      720 resections were performed, and 210 papillary carcinomas were identified that
      were the reason for the excision. The mean size of these tumors decreased from
      2.1 cm to 1.7 cm (P=0.018) over the period of the study, and the percentage of
      tumors measuring <or=1.0 cm increased from 21% to 39% (P=0.007). The vast
      majority of these small tumors (73%) were identified by preoperative fine-needle
      aspiration. During the same period, there were 62 incidental papillary
      carcinomas, 94% of which measured <or=0.5 cm. CONCLUSIONS: The size of papillary
      thyroid carcinomas that were resected at the author's institution decreased
      significantly, and carcinomas measuring <or=1.0 cm increased significantly.
      Currently, papillary carcinomas that measure between 0.5 cm and 1.0 cm rarely are
      either occult or incidental findings in the majority of patients.

PMID- 15986396
TI  - UGT1A1 polymorphisms are important determinants of dietary carcinogen
      detoxification in the liver.
AB  - PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine), the most abundant
      heterocyclic amine in diet, is involved in the etiology of cancer. PhIP and its
      carcinogenic metabolite N-hydroxy-PhIP (N-OH-PhIP) are extensively conjugated by
      UDP-glucuronosyltransferase (UGTs) with wide variability. This study aimed to
      determine the genetic influence of UGTs on the hepatic detoxification of this
      carcinogen. The formation of N-OH-PhIP glucuronides was studied in 48 human liver
      samples by mass spectrometry. Liver samples were genotyped for common
      polymorphisms and correlated with UGT protein levels and N-OH-PhIP
      glucuronidation activities. The formation of four different N-OH-PhIP glucuronide
      metabolites was observed in all livers. The major metabolite was N-OH-PhIP-N(2)
      glucuronide (N(2)G), which is the primary metabolite found in human urine, and
      showed a high interindividual variability (up to 28-fold). Using an heterologous
      expression system, the bilirubin-conjugating UGT1A1 enzyme was identified among
      all known UGTs (n = 16) as the predominant enzyme involved. The significant
      correlation between UGT1A1 protein content and formation of N(2)G (Rs = 0.87; P <
      .0001) suggests a critical role for UGT1A1 in the hepatic metabolism of this
      carcinogen. UGT1A1 expression was strongly determined by the presence of the
      common promoter polymorphisms, UGT1A1*28 (TATA box polymorphism) (P = .0031), 
      3156G/A (P = .0006) and -3279G/T (P = .0017), and rates of N(2)G were indeed
      correlated with these polymorphisms (P < .05), whether analyzed individually or
      in combination (haplotypes). In conclusion, UGT1A1 polymorphisms modulate the
      hepatic metabolism of the carcinogenic intermediate of PhIP and may determine the
      level of its exposure and potentially influence the risk of cancer through
      dietary exposure to HCAs.

PMID- 15986397
TI  - Cytologic features and diagnostic pitfalls of primary ampullary tumors by
      endoscopic ultrasound-guided fine-needle aspiration biopsy.
AB  - BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS
      guided FNAB) is highly sensitive and specific in cytologic diagnosis and clinical
      staging of malignant neoplasms of the gastrointestinal tract, pancreas, liver,
      and lymph nodes. However, no study has been performed to evaluate its accuracy,
      sensitivity, specificity, and the cytomorphologic features of suspected primary
      ampullary tumors. METHODS: All EUS-guided FNABs of suspected primary ampullary
      lesions at the University of California Irvine Medical Center (Orange, CA) from
      January 1998 to September 2004 were retrospectively retrieved. The number of
      passes necessary to arrive at a preliminary diagnosis during adequacy assessment
      was documented. The cytologic features were analyzed with endosonographic
      correlation. Follow-up information was also collected. RESULTS: Thirty-five
      patients were found, 17 men and 18 women. The mean age of the patients was 68.9
      years (range, 34-87 yrs). Adenocarcinoma was diagnosed in 13 patients. Atypical
      cells were found in six patients, four of which were suspicious for
      adenocarcinoma and two of which were consistent with reactive atypia. Adenoma was
      diagnosed in two patients and carcinoid tumor in one. Thirteen patients had a
      diagnosis that was negative for malignant cells. The average number of aspiration
      passes was 2.4 (range, 1-6 passes). Follow-up information was available in 27
      patients. There were three false-negative results and no false-positive results.
      The sensitivity, specificity, and the positive and the negative predictive values
      were 82.4%, 100%, 100%, and 76.9%, respectively. The diagnostic accuracy was
      88.8%. The consistent cytologic features in specimens that were positive or
      suspicious for adenocarcinoma included high cellularity, single cells, 3
      dimensional cell balls, high nuclear-to-cytoplasmic ratio, prominent nucleoli,
      coarse/uneven distribution of chromatin, and necrosis. CONCLUSIONS: EUS-guided
      FNAB was accurate, sensitive, and specific in the assessment of suspected primary
      ampullary masses. Adenoma presented a diagnostic challenge and endosonographic
      correlation was instrumental to increase the diagnostic accuracy.

PMID- 15986398
TI  - Cytologic diagnosis of Burkitt lymphoma.
AB  - BACKGROUND: The diagnosis and classification of lymphoma require correlation of
      morphologic, immunophenotypic, and molecular-cytogenetic studies. Fine-needle
      aspiration biopsy (FNAB) is a valuable diagnostic technique that allows material
      to be collected for these ancillary studies, and for morphologic evaluation.
      METHODS: The authors report a series of seven cases clinically or morphologically
      suspicious for Burkitt lymphoma. Fluorescence in situ hybridization studies
      (FISH) for c-myc were performed on FNAB material and correlated with cytologic
      and immunophenotypic data. RESULTS: Six of seven specimens were positive for c
      myc rearrangement by FISH. However, only three of these cases represented Burkitt
      lymphoma, with one additional case of atypical Burkitt lymphoma. The other cases
      included diffuse large B-cell lymphoma, monomorphic posttransplant B-cell
      lymphoma, and an aggressive B-cell lymphoma, with the latter case negative for c
      myc rearrangement by FISH. Of 2 non-Burkitt lymphoma specimens tested, 1 was
      positive for the immunoglobulin H/bcl-2 rearrangement, in addition to the c-myc
      rearrangement, suggesting transformation from a lower grade lymphoma.
      CONCLUSIONS: These cases illustrated the value of FNAB in the diagnosis of
      Burkitt lymphoma, as well as the importance of obtaining material for, and
      integrating results of, ancillary studies for the final diagnosis.

PMID- 15986399
TI  - Phase II study of tariquidar, a selective P-glycoprotein inhibitor, in patients
      with chemotherapy-resistant, advanced breast carcinoma.
AB  - BACKGROUND: The primary objective of this study was to determine whether addition
      of the selective P-glycoprotein (P-gp) inhibitor tariquidar (XR9576) to
      chemotherapy could induce an objective tumor response in patients who previously
      were resistant to the same agents. The secondary objectives were to evaluate P-gp
      expression by immunohistochemistry (IHC), to determine functional activity of the
      P-gp transporter before and after administration of tariquidar with serial
      technetium-99m ((99m)Tc)-sestamibi scans, and to correlate those parameters with
      clinical response. METHODS: Seventeen women with Stage III-IV breast carcinoma
      were included in the study who progressed (n = 13 women) or had stable disease (n
      = 4 women) on doxorubicin-containing or taxane-containing chemotherapy regimens.
      During the study, the same chemotherapy was continued without dose modifications,
      but tariquidar (150 mg intravenously) was added to the treatment regimen.
      RESULTS: Thirty-six percent of patients had P-gp-positive tumors by IHC, and 5
      patients (29%) experienced increases > or = 10% in sestamibi uptake (median
      increase, 40%; range, 10-63%) after the administration of tariquidar. There was
      one partial response in a patient who had the greatest increase in sestamibi
      uptake and who also showed inducible P-gp expression. There was one patient who
      experienced severe doxorubicin/docetaxel-related toxicity after tariquidar was
      added to her chemotherapy regimen. CONCLUSIONS: Tariquidar showed limited
      clinical activity to restore sensitivity to anthracycline or taxane chemotherapy.
      Functional imaging of the tumor with (99m)Tc-sestamibi scans before and after
      administration of multidrug-resistance inhibitor may be useful to identify the
      small subset of patients who could benefit from multidrug-resistance modulation
      in future trials.

PMID- 15986400
TI  - Predictors and outcomes of surgeons' referral of older breast cancer patients to
      medical oncologists.
AB  - BACKGROUND: Older women are less likely than younger women to receive definitive
      care for a new diagnosis of breast cancer, but the reasons are not well
      understood. Although coordination of referral among specialists is an important
      component of quality of care, it has not been studied as a factor that
      contributes to observed age-related variations in breast cancer care. METHODS:
      Treatment recommendations by 191 surgeons of 559 patients aged > or = 65 years
      with Stage I to IIIa breast cancer provided patient-specific assessments of
      comorbidity and medical oncologist referral. Demographic, tumor, and treatment
      characteristics from medical records and telephone interviews were evaluated by
      statistical regression methods to identify factors associated with referral to a
      medical oncologist and to evaluate whether a referral resulted in discussion and
      prescription of tamoxifen. RESULTS: Estrogen receptor protein negativity and
      higher tumor stage increased the likelihood of referral (odds ratio [OR] = 5.6,
      95% confidence interval [CI] = 1.9-16.7, and OR = 4.2, 95% CI = 1.7-10.3,
      respectively), whereas a moderate to severely ill health status decreased the
      likelihood of referral (OR = 0.4, 95% CI = 0.2-0.9). Those referred were twice as
      likely to report having a discussion about tamoxifen (OR = 2.0, 95% CI = 1.06
      3.7) and to have been prescribed tamoxifen (OR = 2.1, 95% CI = 0.99-4.3).
      CONCLUSIONS: Referral to medical oncologists is associated with receipt of
      adjuvant tamoxifen therapy. The current study findings suggest that more
      consistent referral of older women to medical oncologists may enhance quality of
      discussion and participation in decisions concerning treatment options.

PMID- 15986401
TI  - Improving the quality of life of patients with prostate carcinoma: a randomized
      trial testing the efficacy of a nurse-driven intervention.
AB  - BACKGROUND: Treatments for clinically localized prostate carcinoma are
      accompanied by sexual, urinary, and bowel dysfunction and other sequelae that can
      result in significant distress and reduced well being. Methods capable of
      improving quality of life are needed that can be integrated into clinical
      practice. To address this need, a nurse-driven, cancer care intervention was
      developed and tested. METHODS: Within 6 weeks after completing treatment, 99
      patients, along with their partners, were enrolled into a prospective, controlled
      trial and were randomized to receive the cancer care intervention or to receive
      standard care. Participants in the intervention arm met once each month for 6
      months with an oncology nurse intervenor, who helped patients identify their
      quality-of-life needs using an interactive computer program. The intervener then
      provided education and support tailored to participants' needs. Primary outcome
      variables included 1) disease-specific quality of life, including sexual,
      urinary, and bowel outcomes and cancer worry; 2) depression; 3) dyadic
      adjustment; and 4) general quality of life. Outcomes data were collected prior to
      randomization and again at 4 months, 7 months, and 12 months posttreatment.
      RESULTS: Patients in the intervention arm experienced long-term improvements in
      quality-of-life outcomes related to sexual functioning and cancer worry compared
      with patients who received standard care. Baseline depression moderated the
      impact of the intervention on several other quality-of-life outcomes.
      CONCLUSIONS: The findings of the current study indicated that a computer
      assisted, nurse-driven intervention was capable of providing durable improvements
      in the quality of life of men who underwent treatment for clinically localized
      prostate carcinoma.

PMID- 15986402
TI  - Biofumigation: environmental impacts on the biological activity of diverse pure
      and plant-derived isothiocyanates.
AB  - Four pure isothiocyanates (methyl, 2-propenyl, benzyl and 2-phenylethyl
      isothiocyanate), hydrolysing tissue of two brassicas rich in either 2-propenyl or
      2-phenylethyl isothiocyanate, and the methyl isothiocyanate-generating pesticide
      metam-sodium were tested in vapour exposure tests for biological activity against
      a model soil insect both in vitro and in the presence of three contrasting soils
      and under four temperatures from 5 to 20 degrees C. The purpose was to develop an
      understanding of the factors controlling isothiocyanate release and maintenance
      in soil in order to identify advantageous attributes to seek in utilising
      brassicas for isothiocyanate-based biofumigation. Methyl isothiocyanate,
      structurally the simplest and the most volatile, was the most biologically active
      isothiocyanate under all conditions. It was less affected by the presence of soil
      and by lower temperature than the longer-chain aliphatic 2-propenyl
      isothiocyanate. The activity of the less volatile aromatic isothiocyanates was
      reduced much more by soil, with a decline up to many thousand-fold in the
      presence of soil with high organic matter content at lower temperature. Metam
      sodium closely reflected the methyl isothiocyanate results. The results indicate
      that brassicas rich in aliphatic isothiocyanates are more likely to have the
      potential to exert stronger isothiocyanate-based biofumigation effects than those
      similarly rich in aromatic isothiocyanates.

PMID- 15986403
TI  - Primary iron overload with inappropriate hepcidin expression in V162del
      ferroportin disease.
AB  - Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of
      human iron metabolism, characterized by iron deposition in macrophages, including
      Kupffer cells. Mutations in the gene encoding ferroportin 1, a cellular iron
      exporter, are responsible for this iron storage disease, inherited as an
      autosomal dominant trait. We present clinical, histopathological, and
      radiological findings in a family with the most common ferroportin mutation,
      V162del. In the index case, the disorder is characterized by abundant deposition
      of hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric
      and duodenal mucosa, and also in squamous cell carcinoma of the lung). The
      radiological findings indicated the presence of excess iron in bone marrow and
      spleen. Despite a significant burden of iron, no features of chronic liver
      disease were found in affected members of the family, including individuals aged
      up to 80 years. Hyperferritinemia greater than 1,000 microg/L was a penetrant
      biochemical finding before the second decade in life and was associated with
      significantly increased serum concentrations of pro-hepcidin that correlated
      positively with urinary hepcidin concentrations. In conclusion, the systemic iron
      burden in ferroportin disease is not a sufficient cause for chronic liver
      disease. In patients with most, but not all, ferroportin mutations, retention of
      iron in macrophages of the liver and other organs may protect against damage to
      parenchymal cells. Finally, macrophage iron storage in ferroportin disease is
      associated with elevated serum pro-hepcidin levels.

PMID- 15986404
TI  - Symmetry-breaking in mammalian cell cohort migration during tissue pattern
      formation: role of random-walk persistence.
AB  - Coordinated, cohort cell migration plays an important role in the morphogenesis
      of tissue patterns in metazoa. However, individual cells intrinsically move in a
      random walk-like fashion when studied in vitro. Hence, in the absence of an
      external orchestrating influence or template, the emergence of cohort cell
      migration must involve a symmetry-breaking event. To study this process, we used
      a novel experimental system in which multiple capillary endothelial cells exhibit
      spontaneous and robust cohort migration in the absence of chemical gradients when
      cultured on micrometer-scale extracellular matrix islands fabricated using
      microcontact printing. A computational model suggested that directional
      persistence of random-walk and dynamic mechanical coupling of adjacent cells are
      the critical control parameters for this symmetry-breaking behavior that is
      induced in spatially-constrained cell ensembles. The model predicted our finding
      that fibroblasts, which exhibit a much shorter motility persistence time than
      endothelial cells, failed to undergo symmetry breaking or produce cohort
      migration on the matrix islands. These findings suggest that cells have intrinsic
      motility characteristics that are tuned to match their role in tissue patterning.
      Our results underscore the importance of studying cell motility in the context of
      cell populations, and the need to address emergent features in multicellular
      organisms that arise not only from cell-cell and cell-matrix interactions, but
      also from properties that are intrinsic to individual cells.

PMID- 15986405
TI  - Chicken gizzard filamin, retina filamin and cgABP260 are respectively, smooth
      muscle-, non-muscle- and pan-muscle-type isoforms: distribution and localization
      in muscles.
AB  - We determined the full cDNA sequences of chicken gizzard filamin and cgABP260
      (chicken gizzard actin-binding protein 260). The primary and secondary structures
      predicted by these sequences were similar to those of chicken retina filamin and
      human filamins. Like mammals, chickens have 3 filamin isoforms. Comparison of
      their amino acid sequences indicated that gizzard filamin, retina filamin, and
      cgABP260 were the counterparts of human FLNa (filamin a), b, and c, respectively.
      Antibodies against the actin-binding domain (ABD) of these 3 filamin isoforms
      were raised in rabbits. Using immunoabsorption and affinity chromatography, we
      prepared the monospecific antibody against the ABD of each filamin. In
      immunoblotting, the antibody against the gizzard filamin ABD detected a single
      band in gizzard, but not in striated muscles or brain. In brain, only the
      antibody against the retina filamin ABD produced a strong single band. The
      antibody against the cgABP260 ABD detected a single peptide band in smooth,
      skeletal, and cardiac muscle. In immunofluorescence microscopy of muscular
      tissues using these antibodies, the antibody against the gizzard filamin ABD only
      stained smooth muscle cells, and the antibody against the retina filamin ABD
      strongly stained endothelial cells of blood vessels and weakly stained cells in
      connective tissue. The antibody against the cgABP260 ABD stained the Z-lines and
      myotendinous junctions of breast muscle, the Z-lines and intercalated disks of
      cardiac muscle, and dense plaques of smooth muscle. These findings indicate that
      chicken gizzard filamin, retina filamin, and cgABP260 are, respectively, smooth
      muscle-type, non-muscle-type, and pan-muscle-type filamin isoforms.

PMID- 15986406
TI  - Long- and short-term plasticity at mossy fiber synapses on mossy cells in the rat
      dentate gyrus.
AB  - Mossy cells give rise to the commissural and associational pathway of the dentate
      gyrus, and receive their major excitatory inputs from the mossy fibers of granule
      cells. Through these feed-back excitatory connections, mossy cells have been
      suggested to play important roles in both normal signal processing in learning
      and memory, as well as in seizure propagation. However, the nature of the
      activity-dependent modifications of the mossy fiber inputs to mossy hilar cells
      is not well understood. We studied the long- and short-term plasticity properties
      of the mossy fiber-mossy cell synapse, using the minimal stimulation technique in
      slices in whole cell recorded mossy cells retrogradely prelabeled with the
      fluorescent dye DiO from the contralateral dentate gyrus. Following tetanic
      stimulation, mossy fiber synapses showed significant NMDA receptor-independent
      long-term potentiation (LTP), associated with increased excitatory postsynaptic
      currents (EPSC) amplitude and decreased failure rates. Coefficient of variance
      and failure rate analyses suggested a presynaptic locus of LTP induction. Mossy
      fiber synapses on mossy cells also showed activity-dependent short-term
      modification properties, including both frequency-dependent facilitation (stimuli
      at higher frequencies evoked larger EPSCs with lower failure rates) and burst
      facilitation (each EPSC in a burst had a larger amplitude and higher probability
      of occurrence than the preceding EPSCs within the burst). The data show that
      mossy fiber-mossy cell synapses exhibit both long- and short-term plasticity
      phenomena that are generally similar to the mossy fiber synapses on CA3 pyramidal
      cells.

PMID- 15986407
TI  - A computational principle for hippocampal learning and neurogenesis.
AB  - In the three decades since Marr put forward his computational theory of
      hippocampal coding, many computational models have been built on the same key
      principles proposed by Marr: sparse representations, rapid Hebbian storage,
      associative recall and consolidation. Most of these models have focused on either
      the CA3 or CA1 fields, using "off-the-shelf" learning algorithms such as
      competitive learning or Hebbian pattern association. Here, we propose a novel
      coding principle that is common to all hippocampal regions, and from this one
      principal, we derive learning rules for each of the major pathways within the
      hippocampus. The learning rules turn out to have much in common with several
      models of CA3 and CA1 in the literature, and provide a unifying framework in
      which to view these models. Simulations of the complete circuit confirm that both
      recognition memory and recall are superior relative to a hippocampally lesioned
      model, consistent with human data. Further, we propose a functional role for
      neurogenesis in the dentate gyrus (DG), namely, to create distinct memory traces
      for highly similar items. Our simulation results support our prediction that
      memory capacity increases with the number of dentate granule cells, while
      neuronal turnover with a fixed dentate layer size improves recall, by minimizing
      interference between highly similar items.

PMID- 15986408
TI  - Word imageability affects the hippocampus in recognition memory.
AB  - Concrete words, whose meanings are readily imagined, are better remembered than
      abstract words. However, the neural correlates of this effect are poorly
      understood. Here, we investigated the effect of imageability on brain activity in
      the medial temporal lobe (MTL) processes underlying recognition memory. We
      recorded event-related potentials (ERPs) via depth electrodes from within the MTL
      in 14 patients with drug-resistant epilepsy. Patients performed a continuous word
      recognition task with words of high and low imageability (controlled for word
      frequency). Behaviorally, recognition performance was better for high, compared
      to low, imageable words. Two ERP components associated with recognition memory,
      the AMTL-N400 and the hippocampal late negative component, showed an old/new
      effect, but only the hippocampal P600 showed a main effect of imageability. We
      suggest that the hippocampal effect of imageability in recognition memory may be
      associated with conceptual or pictorial information processing of concrete words.

PMID- 15986409
TI  - Structural variation in the inner ears of four deep-sea elopomorph fishes.
AB  - Deep-sea fishes have evolved in dark or dimly lit environments devoid of the
      visual cues available to shallow-water species. Because of the limited
      opportunity for visual scene analysis by deep-sea fishes, it is reasonable to
      hypothesize that the inner ears of at least some such species may have evolved
      structural adaptations to enhance hearing capabilities in lieu of vision. As an
      initial test of this hypothesis, scanning electron microscopy was used to examine
      the structure of the inner ears of four deep-sea elopomorph species inhabiting
      different depths: Synaphobranchus kaupii, Synaphobranchus bathybius,
      Polyacanthonotus challengeri, and Halosauropsis macrochir. The shape of the
      sensory epithelia and hair cell ciliary bundle orientation of the saccule,
      lagena, and utricle, the three otolithic organs associated with audition and
      vestibular function, are described. The saccules of all four species have a
      common, alternating ciliary bundle orientation pattern. In contrast, the lagena
      exhibits more interspecific diversity in shape and ciliary bundle orientation,
      suggesting that it has special adaptations in these species. The macula neglecta,
      a sensory epithelium of unknown function, is present in all four species.

PMID- 15986410
TI  - Immunocytochemistry of the nervous system and the musculature of the chordoid
      larva of Symbion pandora (Cycliophora).
AB  - To date, the phylum Cycliophora comprises only one described extant species of
      acoelomate marine invertebrates, Symbion pandora. Adult specimens live
      commensally on the mouthparts of the Norwegian lobster, Nephrops norvegicus. Its
      complicated life cycle includes an asexually produced Pandora larva and a
      sexually produced chordoid larva. Despite detailed TEM investigations and its
      inclusion in recent molecular phylogenetic analyses, cycliophoran relationships
      still remain enigmatic. In order to increase the morphological database, I
      investigated the anatomy of the nervous system and the musculature of the
      chordoid larva by applying fluorescence-coupled antibodies against the
      neurotransmitters serotonin and FMRFamide, as well as FITC-coupled phalloidin to
      label filamentous F-actin, in combination with confocal laser scanning
      microscopy. The FMRFamidergic nervous system shows a bilobed anterior ganglion
      and one pair of ventral nerve cords, while serotonin is distributed in a
      scattered pattern in the anterior ganglion. In addition, there are two pairs of
      ventral serotonergic nerves, of which the inner pair fuses with the outer nerve
      cords in the posterior third of the larva. The musculature comprises an outer
      layer of six units of circular body wall muscles, several helicoid muscle fibers,
      a set of paired longitudinal muscles that span the entire anterior-posterior axis
      of the larva, and a few oblique muscle strands. Furthermore, an anterior muscle
      complex and one pair of posterior muscles are present. The chordoid organ
      consists of a number of distinct subunits that are each formed by a dense layer
      of circular muscle fibers. The overall arrangement of the oblique and
      longitudinal muscles as well as the body wall musculature in the chordoid larva
      of Symbion pandora exhibits similarities with the condition found in certain
      rotifers. This is congruent with some recent phylogenies based on 18S rRNA
      sequences but additional morphological, developmental, and molecular data are
      needed to clarify the phylogenetic relationships of Cycliophora.

PMID- 15986412
TI  - Methotrexate induction of human sulfotransferases in Hep G2 and Caco-2 cells.
AB  - Methotrexate (MTX) was the first antifolate drug developed for the treatment of
      cancer. It is also effective in treating inflammatory and autoimmune diseases.
      Sulfotransferases are phase II drug-metabolizing enzymes and their induction by
      hormones and endogenous molecules is relatively well known, although xenobiotic
      drug induction of sulfotransferases has not been well studied. In the present
      investigation, MTX is shown to be a xenobiotic inducer of human sulfotransferases
      in transformed human liver (Hep G2) and intestinal (Caco-2) cells. Following MTX
      treatment, various sulfotransferases were induced in both cell lines. Enzyme
      assay, Western blot and reverse-transcription polymerase chain reaction (RT-PCR)
      results demonstrated that protein and mRNA expressions of human simple phenol
      sulfotransferase (P-PST), human monoamine sulfotransferase (M-PST), human
      dehydroepiandrosterone sulfotransferase (DHEA-ST) and human estrogen
      sulfotransferase (EST) were induced in Hep G2 cells; M-PST and DHEA-ST were
      induced in Caco-2 cells. Inductions in both cell lines were dose dependent.
      Enzyme activity and Western blot results were in good agreement with RT-PCR
      results, suggesting that the induction is at the gene transcription level. Folic
      acid had a significantly lesser effect on sulfotransferases compared with MTX.
      Interestingly, the induction of different sulfotransferases by MTX was inhibited
      by high doses of folic acid at both protein and mRNA levels in Hep G2 cells.
      Methotrexate is the first antifolate and apoptosis-inducing drug to show
      induction of sulfotransferases in Hep G2 cells and Caco-2 cells. The inhibition
      by folic acid suggests a possible mechanism for MTX induction.

PMID- 15986413
TI  - Popliteal lymph node assay: facts and perspectives.
AB  - The popliteal lymph node assay (PLNA) derives from the hypothesis that some
      supposedly immune-mediated adverse effects induced by certain pharmaceuticals
      involve a mechanism resembling a graft-versus-host reaction. The injection of
      many but not all of these compounds into the footpad of mice or rats produces an
      increase in the weight and/or cellularity of the popliteal lymph node in the
      treated limb (direct PLNA). Some of the compounds known to cause these adverse
      effects in humans, however, failed to induce a positive PLNA response, leading to
      refinements of the technique to include pretreatment with enzyme inducers,
      depletion of CD4(+) T cells or additional endpoints such as histological
      examination, lymphocyte subset analysis and cytokine fingerprinting. Alternative
      approaches have been used to improve further the predictability of the assay. In
      the secondary PLNA, the test compound is injected twice in order to illicit a
      greater secondary response, thus suggesting a memory-specific T cell response. In
      the adoptive PLNA, popliteal lymph node cells from treated mice are injected into
      the footpad of naive mice; a marked response to a subsequent footpad challenge
      demonstrates the involvement of T cells. Finally, the reporter antigens TNP
      Ficoll and TNP-ovalbumin are used to differentiate compounds that induce
      responses involving neo-antigen help or co-stimulatory signals (modified PLNA).
      The PLNA is increasingly considered as a tool for detection of the potential to
      induce both sensitization and autoimmune reactions. A major current limitation is
      validation. A small inter-laboratory validation study of the direct PLNA found
      consistent results. No such study has been performed using an alternative
      protocol. Other issues include selection of the optimal protocol for an improved
      prediction of sensitization vs autoimmunity, and the elimination of false
      positive responses due to primary irritation. Finally, a better understanding of
      underlying mechanisms is essential to determine the most relevant endpoints. The
      confusion resulting from use of the PLNA to predict autoimmune-like reactions as
      well as sensitization should be clarified. Interestingly, most drugs that were
      positive in the direct PLNA are also known to cause drug hypersensitivity
      syndrome in treated patients. This observation is expected to open new avenues of
      research.

PMID- 15986414
TI  - CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and
      elimination pathways in mice.
AB  - Induction of hepatic phase I/II detoxification enzymes and alternative excretory
      pumps may limit hepatocellular accumulation of toxic biliary compounds in
      cholestasis. Because the nuclear xenobiotic receptors constitutive androstane
      receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and
      transporters, we aimed to induce adaptive alternative pathways with different CAR
      and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital
      and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists
      atorvastatin and pregnenolone-16alpha-carbonitrile. Hepatic bile acid and
      bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Cyp3a11, Ugt1a1, Sult2a1),
      their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile
      acid/organic anion and lipid transporters (Ntcp, Oatp1,2,4, Bsep, Mrp2-4, Mdr2,
      Abcg5/8, Asbt) in the liver and kidney were analyzed via reverse-transcriptase
      polymerase chain reaction and Western blotting. Potential functional relevance
      was tested in common bile duct ligation (CBDL). CAR agonists induced Mrp2-4 and
      Oatp2; PXR agonists induced only Mrp3 and Oatp2. Both PXR and CAR agonists
      profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and
      Cyp2b10. In addition, CAR agonists upregulated bile acid-sulfating Sult2a1 and
      bilirubin-glucuronidating Ugt1a1. These changes were accompanied by reduced serum
      levels of bilirubin and bile acids in healthy and CBDL mice and by increased
      levels of polyhydroxylated bile acids in serum and urine of cholestatic mice.
      Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other
      transporters and enzymes were moderately affected. In conclusion, administration
      of specific CAR or PXR ligands results in coordinated stimulation of major
      hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key
      alternative efflux systems, effects that are predicted to counteract cholestasis.

PMID- 15986415
TI  - Predicting cirrhosis in patients with hepatitis C based on standard laboratory
      tests: results of the HALT-C cohort.
AB  - Knowledge of the presence of cirrhosis is important for the management of
      patients with chronic hepatitis C (CHC). Most models for predicting cirrhosis
      were derived from small numbers of patients and included subjective variables or
      laboratory tests that are not readily available. The aim of this study was to
      develop a predictive model of cirrhosis in patients with CHC based on standard
      laboratory tests. Data from 1,141 CHC patients including 429 with cirrhosis were
      analyzed. All biopsies were read by a panel of pathologists (blinded to clinical
      features), and fibrosis stage was determined by consensus. The cohort was divided
      into a training set (n = 783) and a validation set (n = 358). Variables that were
      significantly different between patients with and without cirrhosis in univariate
      analysis were entered into logistic regression models, and the performance of
      each model was compared. The area under the receiver-operating characteristic
      curve of the final model comprising platelet count, AST/ALT ratio, and INR in the
      training and validation sets was 0.78 and 0.81, respectively. A cutoff of less
      than 0.2 to exclude cirrhosis would misclassify only 7.8% of patients with
      cirrhosis, while a cutoff of greater than 0.5 to confirm cirrhosis would
      misclassify 14.8% of patients without cirrhosis. The model performed equally well
      in fragmented and nonfragmented biopsies and in biopsies of varying lengths. Use
      of this model might obviate the requirement for a liver biopsy in 50% of patients
      with CHC. In conclusion, a model based on standard laboratory test results can be
      used to predict histological cirrhosis with a high degree of accuracy in 50% of
      patients with CHC.

PMID- 15986416
TI  - S100b counteracts effects of the neurotoxicant trimethyltin on astrocytes and
      microglia.
AB  - Central nervous system degenerative diseases are often characterized by an early,
      strong reaction of astrocytes and microglia. Both these cell types can play a
      double role, protecting neurons against degeneration through the synthesis and
      secretion of trophic factors or inducing degeneration through the secretion of
      toxic molecules. Therefore, we studied the effects of S100B and trimethyltin
      (TMT) on human astrocytes and microglia with two glial models, primary cultures
      of human fetal astrocytes and a microglia cell line. After treatment with 10(-5)
      M TMT, astrocytes showed morphological alterations associated with an increase in
      glial fibrillary acidic protein (GFAP) expression and changes in GFAP filament
      organization. Administration of S100B before TMT treatment prevented TMT-induced
      changes in morphology and GFAP expression. A decrease in inducible nitric oxide
      synthase expression was observed in astrocytes treated with TMT, whereas the same
      treatment induced iNOS expression in microglia. In both cases, S100B prevented
      TMT-induced changes. Tumor necrosis factor-alpha mRNA expression in astrocytes
      was not modified by TMT treatment, whereas it was increased in microglia cells.
      S100B pretreatment blocked the TMT-induced increase in TNF-alpha expression in
      microglia. To trace the mechanisms involved in S100B activity, the effect of BAY
      11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB) activation, and of
      PD98059, an inhibitor of MEK-ERK1/2, were investigated. Results showed that the
      protective effects of S100B against TMT toxicity in astrocytes depend on NF
      kappaB, but not on ERK1/2 activation. These results might help in understanding
      the role played by glial cells in brain injury after exposure to chemical
      neurotoxicants and support the view that S100B may protect brain cells in case of
      injury. (c) 2005 Wiley-Liss, Inc.

PMID- 15986418
TI  - Worsening after rituximab treatment in anti-mag neuropathy.

PMID- 15986419
TI  - Variability of motor unit discharge and force fluctuations across a range of
      muscle forces in older adults.
AB  - Variability of motor unit discharge is a likely contributor to the greater force
      fluctuations observed in old adults at low muscle forces. We sought to determine
      whether the variability of motor unit discharge rate underlies the fluctuations
      in force during steady contractions across a range of forces in young (n = 11)
      and old (n = 14) adults. The coefficient of variation (CV) for discharge rate and
      force were measured during a force-matching task as the first dorsal interosseous
      muscle performed isometric contractions. The recruitment thresholds of the 78
      motor units ranged from 0.04% to 34% of maximal voluntary contraction (MVC)
      force. The CV for discharge rate ranged from 7.6% to 46.2% and was greater (P <
      0.05) for old adults (21.5% +/- 7.7%) than young adults (17.3% +/- 8.1%).
      Although the CV for force was similar for young and old subjects (2.53% +/- 1.6%)
      across all target forces, it was greater for old adults at the lowest forces.
      Furthermore, there was a positive relation (r2 = 0.20, P < 0.001) between the CV
      for force and the CV for discharge rate across the range of recruitment
      thresholds. This relation was significant for old adults (r2 = 0.30, P < 0.001),
      but not for young adults (r2 = 0.06, P > 0.05). Thus, the normalized variability
      (CV) of motor unit discharge was greater in old adults and was related to the
      amplitude of force fluctuations across a broader range of forces than previously
      examined. These findings underscore the contribution of variability of motor unit
      activity to motor output in normal human aging.

PMID- 15986420
TI  - A pilot tolerability and efficacy trial of sodium oxybate in ethanol-responsive
      movement disorders.
AB  - Sodium oxybate is currently approved in the United States exclusively for the
      treatment of cataplexy in narcoleptic patients. In a prior article published in
      this journal, we reported a patient with severe posthypoxic myoclonus whose
      myoclonus improved with ethanol and also with treatment with sodium oxybate. We
      extend this preliminary observation to five other patients with ethanol
      responsive movement disorders in an open-label, dose-titration, add-on, 8-week
      trial. All five patients (one with severe alcohol-responsive posthypoxic
      myoclonus, two with epsilon-sarcoglycan-linked myoclonus-dystonia, and two with
      essential tremor) experienced improvement from baseline of 50% or greater as
      measured by blinded videotape review. Tolerability was satisfactory, with dose
      dependent sedation as the most common side effect. Further studies of this drug
      in hyperkinetic movement disorders are warranted.

PMID- 15986421
TI  - Kufor Rakeb disease: autosomal recessive, levodopa-responsive parkinsonism with
      pyramidal degeneration, supranuclear gaze palsy, and dementia.
AB  - Kufor Rakeb disease is an autosomal recessive disorder characterized by subacute,
      juvenile-onset, levodopa-responsive parkinsonism, pyramidal signs, dementia, and
      a supranuclear gaze palsy. It was originally described more than a decade ago,
      and linkage analysis identified a locus on chromosome 1p36 that was previously
      assigned PARK9. We have further characterized the clinical picture and
      specifically re-assessed the response to levodopa in the original family, in the
      northern highlands of Jordan. In the 4 surviving patients, there has been a
      narrowing of the therapeutic window for levodopa with the emergence of peak-dose
      dyskinesias with increased spasticity and cognitive decline. Several new features
      were identified, including facial-faucial-finger mini-myoclonus, visual
      hallucinations, and oculogyric dystonic spasms.

PMID- 15986422
TI  - Alterations of striatal neurons in benign hereditary chorea.
AB  - Benign hereditary chorea (BHC) recently has been associated with mutations in
      TITF-1 gene, although a pathological study of an individual with BHC and a TITF-1
      mutation revealed no significant gross or microscopic abnormalities using
      standard methods. Immunohistochemical staining of striatal tissue from a BHC
      affected postmortem brain was performed using antibodies against
      neurotransmitters of interneurons whose tangential migration is mediated by TITF
      1. There was a loss of most TITF-1-mediated striatal interneurons in the BHC
      specimen compared to four matched control brains.

PMID- 15986423
TI  - Dystonia and parkinsonism in GM1 type 3 gangliosidosis.
AB  - GM1 gangliosidosis is due to beta-galactosidase deficiency. Only patients with
      type 3 disease survive into adulthood and develop movement disorders. Clinical
      descriptions of this form are rare, particularly in non-Japanese patients. We
      describe four new patients and systematically analyze all previous reports found
      by a literature search and contacts with the authors for additional information.
      Generalized dystonia remained the predominant feature throughout the disease
      course and was often associated with akinetic-rigid parkinsonism. GM1
      gangliosidosis must be considered as a cause of early-onset generalized dystonia,
      particularly in patients with short stature and skeletal dysplasia.

PMID- 15986424
TI  - In vivo detection of iron and neuromelanin by transcranial sonography: a new
      approach for early detection of substantia nigra damage.
AB  - Early diagnosis of Parkinson's disease (PD) in nonsymptomatic patients is a key
      issue. An increased echogenicity of the substantia nigra (SN) was found
      previously in Parkinsonian patients and in a low percentage of healthy adults.
      These nonsymptomatic subjects also showed a reduced 18F-dopa uptake in striatum,
      suggesting a preclinical injury of the nigrostriatal system that could later
      proceed into PD. To investigate the ability of ultrasonography to detect markers
      of SN degeneration, such as iron deposition and neuromelanin depletion, we
      scanned postmortem brains from normal subjects at different ages by ultrasound
      and measured the echogenic area of the SN. The SN was then dissected and used for
      histological examinations and determination of iron, ferritin, and neuromelanin
      content. A significant positive correlation was found between the echogenic area
      of the SN and the concentration of iron, H- and L-ferritins. Multivariate
      analysis carried out considering the iron content showed a significant negative
      correlation between echogenicity and neuromelanin content of the SN. In PD, a
      typical loss of neuromelanin and increase of iron is observed in this brain area.
      The finding of a positive correlation between iron and ferritin levels and a
      negative correlation of neuromelanin content with the area of echogenicity at the
      SN could therefore provide an interesting basis for diagnosis and therapeutic
      follow-up studies in PD.

PMID- 15986425
TI  - Lifestyle habits as prognostic factors in survival of laryngeal and
      hypopharyngeal cancer: a multicentric European study.
AB  - Little information is available on the role of tobacco, alcohol and diet in the
      survival of upper aero digestive cancers. Our study analysed the survival of 931
      laryngeal and hypopharyngeal cancer patients, enrolled in a population based case
      control study conducted at 5 centres in southeast Europe during 1979-1982. Age at
      the time of diagnosis and site of origin of tumour were observed to be predictors
      of the survival. Cigarette smoking, and to a limited extent alcohol drinking,
      before the diagnosis of tumour seem to influence the overall survival whereas
      high intakes of vegetables and vitamin C were observed to favourably affect the
      prognosis. For mortality from upper aerodigestive cancer protective effects of
      high intakes of vegetables, fibres and vitamin C were observed. Our results
      support the hypothesis that there is a role for dietary intervention to improve
      survival of laryngeal and hypopharyngeal cancer patients.

PMID- 15986426
TI  - Expression of RPIP9 (Rap2 interacting protein 9) is activated in breast carcinoma
      and correlates with a poor prognosis.
AB  - MDR1 is upregulated in many tumors. We have previously detected activation of the
      MDR1 upstream promoter in metastatic breast cancer cells. MDR1 overlaps with an
      uncharacterized gene transcribed from the opposite strand, coding for Rap2
      interacting protein 9 (RPIP9). Rap2 belongs to the Ras superfamily of GTPases,
      whose role in breast cancer remains unknown. We developed sensitive methods for
      detecting and quantifying RPIP9 mRNA and used it to identify these transcripts in
      normal human tissues, 60 biopsies of primary breast carcinoma, in isolated
      epithelial cells both from the primary tumor and from associated lymph nodes, and
      from bone marrow biopsies of 74 breast cancer patients. RPIP9 is expressed at
      high levels in normal testis, brain and adrenal gland, and at very low levels in
      normal breast. Tumorigenic breast carcinoma cell lines expressed RPIP9, whereas
      MCF-10A and HBL-100 that do not form tumors in nude mice had undetectable levels
      of RPIP9 mRNA. RPIP9 was activated in a high proportion of breast carcinomas
      (61.6%; n = 60) and a significant correlation with metastatic lymph node invasion
      (N = 0-3 vs. N > 3, where N = number of lymph nodes invaded; p = 0.031) was
      found. RPIP9 mRNA could be detected in malignant epithelial cells isolated from
      the primary tumor and from metastasized lymph nodes as well as in the bone marrow
      of significantly more poor-prognosis (N > 3) than better-prognosis (N = 0-3)
      patients (p = 0.001). Therefore, activation of RPIP9 occurs during the malignant
      breast epithelial transformation and increases with progression toward an
      invasive phenotype.

PMID- 15986427
TI  - Is birth history the key to highly educated women's higher breast cancer
      mortality? A follow-up study of 500,000 women aged 35-54.
AB  - A positive relationship has been found between high levels of education and
      breast cancer mortality. The aim of our study is to determine if the educational
      gradient in breast cancer mortality persists after adjustment for reproductive
      history. Register data including the total adult population in Norway were used.
      A total of 512,353 Norwegian women 35-54 years of age at the Norwegian Census in
      1990 were followed with respect to breast cancer deaths until December 31, 2001.
      The analysis included 2,052 breast cancer deaths in 5.6 million person years.
      Educational differences in breast cancer mortality were analysed using Cox
      regression. The age adjusted relative risk of dying from breast cancer for women
      with >12 years of education compared to women with <10 years was 1.25 (95%
      confidence limits [CI] = 1.10-1.41). Adjustment for age at first birth with
      nulliparous as reference category reduced this difference to 1.08 (95% CI = 0.95
      1.23). For parous women, age at first birth explained all the educational
      difference in breast cancer mortality. Among nulliparous women there was a larger
      positive educational gradient in breast cancer mortality than among parous women
      (relative risk [RR] = 1.57, 95% CI = 1.15-2.13), indicating that there were
      differences in other confounders than birth history among the childless.

PMID- 15986428
TI  - Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in
      ovarian cancer.
AB  - Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the
      existence of multiple target loci, as the separate gain of chromosome bands 8q21
      and 8q24 has been reported in independent studies. Since tumor protein D52
      (TPD52) has been identified as a chromosome 8q21 amplification target in breast
      and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium
      (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and
      invasive carcinomas of the major histologic subtypes (n = 57) using
      immunohistochemistry. These analyses revealed that all normal ovarian epithelium
      samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52
      was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of
      histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic,
      although nuclear localization was also frequently observed in mucinous and clear
      cell carcinomas. In an independent cohort of stage III serous carcinomas (n =
      18), we also directly compared in situ TPD52 expression using
      immunohistochemistry and TPD52 copy number using interphase FISH analyses. This
      revealed that TPD52 dosage and TPD52 expression were significantly positively
      correlated. TPD52 therefore represents a novel molecular marker in ovarian
      cancer, which is broadly expressed across the different histologic subtypes and
      whose upregulation frequently reflects increased TPD52 copy number.

PMID- 15986429
TI  - Overexpression of the small transmembrane and glycosylated protein SMAGP supports
      metastasis formation of a rat pancreatic adenocarcinoma line.
AB  - Small cell transmembrane and glycosylated protein (SMAGP) was recently identified
      in the metastasizing rat pancreatic adenocarcinoma line BSp73ASML. SMAGP, an
      evolutionary conserved transmembrane protein, is expressed on lateral epithelial
      cell membranes. SMAGP expression was restricted to or was upregulated in several
      metastasizing as compared to nonmetastasizing human and rat tumor lines. In
      contrast to nontransformed tissue, SMAGP was mainly expressed in the cytoplasm,
      as has already been described for high-grade human colorectal cancer. This raised
      the question on the impact of SMAGP on tumor progression. To answer the question,
      metastasis formation was evaluated in the nonmetastasizing rat pancreatic
      adenocarcinoma subline BSp73AS (AS), which was stably transfected with SMAGP cDNA
      (AS-SMAGP). Cytoplasmic SMAGP expression promoted cell agglomeration, but
      inhibited tumor cell proliferation, adhesion to and migration toward vitronectin
      and matrigel invasion, which was accompanied by a failure of actin
      reorganization. AS-SMAGP clones strongly promoted metastasis formation by
      dislodgment of normal tissue; 82% of rats developed lymph node metastasis as
      compared to 22% of rats receiving AS or mock-cDNA-transfected AS cells. The
      incidence of lung metastasis was increased from 6% in AS to 98% in AS-SMAGP tumor
      bearing rats. Thus, SMAGP strongly promotes tumor progression. This likely is due
      to redistribution from the plasma membrane into the cytoplasm. SMAGP
      redistribution does not only facilitate tumor cell detachment from neighboring
      cells and the extracellular matrix, but obviously contributes actively by a not
      yet defined mechanism to tumor cell agglomeration and capillary plugging.

PMID- 15986430
TI  - Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops
      (Humulus lupulus L.) and beer.
AB  - The female inflorescences of the hop plant (Humulus lupulus L.) are essential
      during brewing to add taste and flavor to beer and to stabilize beer foam.
      Xanthohumol, the main prenylated chalcone in hops, was investigated for its
      antiinvasive activity on human breast cancer cell lines (MCF-7 and T47-D) in
      vitro. Xanthohumol was able to inhibit the invasion of MCF-7/6 cells at 5 microM
      in the chick heart invasion assay and of T47-D cells in the collagen invasion
      assay. Xanthohumol inhibited growth of MCF-7/6 and T47-D cells, but not of chick
      heart cells. Moreover, it induced apoptosis of these tumor cells as demonstrated
      by the cleavage of nuclear PARP after 48 hr treatment. To probe the mechanism of
      the antiinvasive effect of xanthohumol, involvement of the E-cadherin/catenin
      invasion-suppressor complex was investigated. An aggregation assay demonstrated
      stimulation of aggregation of MCF-7/6 cells in the presence of 5 microM
      xanthohumol and this could be completely inhibited by an antibody against E
      cadherin. Xanthohumol upregulates the function of the E-cadherin/catenin complex
      and inhibits invasion in vitro, indicating a possible role as an antiinvasive
      agent in vivo as well.

PMID- 15986431
TI  - Incidence of intracranial meningiomas in Denmark, Finland, Norway and Sweden,
      1968-1997.
AB  - It has been reported that the incidence of meningioma increased in several
      industrialized countries in the late 1970s and early 1980s. The aim of this study
      was to evaluate the time trends in incidence of meningiomas in Denmark, Finland,
      Norway and Sweden, with emphasis on the age distribution and sex ratio.
      Information about cases of meningiomas in people aged 15-84 years was obtained
      from the cancer registries of these Nordic countries for the years 1968-1997, and
      estimates of person-years at risk were calculated from information provided by
      the national population registries. Age-specific incidence rates per 100,000 and
      incidence rate ratios were calculated for 3-year periods. The female:male ratios
      were also evaluated. The combined incidence among men increased from 1.4 to 1.9
      per 100,000 during the follow-up period, the corresponding rates for women were
      2.6 and 4.5. The female:male ratio increased over time for several age groups and
      was as high as 3.5:1 in the group aged 40-44 years in the latest follow-up period
      (1993-1997). In summary, our results provide some support for the idea that the
      introduction of computed tomography in the late 1970s has had an impact on the
      detection of cases in people aged 60 and over. The decrease in the rate or
      detection postmortem has affected the incidence time trend, but it also coincides
      with widespread use of new imaging technologies. The increasing trend shown for
      the female:male ratio in the group aged 35-59 years is consistent with the
      possibility that increasing use of hormones may affect the incidence of
      meningiomas in women.

PMID- 15986432
TI  - Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with
      epidermal growth factor receptor mutation type III expression.
AB  - PTEN is a major tumor suppressor gene that has been shown to inhibit cell
      invasion. Its mutation has been found in 20-40% of malignant gliomas. Meanwhile,
      the type III EGFR mutation (EGFRvIII), which was frequently found in gliomas,
      promoted cell invasion. In the present study, the effects of PTEN on cell
      invasion were investigated in U87DeltaEGFR glioblastoma cells with EGFRvIII
      expression but missing PTEN. The cell invasion was downregulated by transfection
      of phosphatase-active forms of PTEN (wild-type and G129E) but not by PTEN (C124A)
      with an inactive phosphatase domain; the effects were correlated with decreased
      tyrosine phosphatase levels of FAK at Tyr397, which was increased by EGFRvIII.
      Overexpression of FAK mutant (Y397F) could partially mimic the effect of PTEN on
      cell invasion. Although EGFRvIII increased the levels of P-Akt and PTEN
      eliminated it, PI-3K inhibitors, wortmannin or Ly294002, could not decrease the
      cell invasion. In conclusion, PTEN could inhibit cell invasion even in the
      presence of the constitutively active EGFR; this inhibition depended on its
      protein phosphatase activity, partially by dephosphorylating FAK, but not
      depended on its lipid phosphatase activity.

PMID- 15986434
TI  - Breast-feeding and childhood cancer: A systematic review with metaanalysis.
AB  - It has been suggested that breast milk may play a role in the prevention of
      certain childhood cancers. We undertook a systematic review of published studies
      investigating the association between breast-feeding and childhood cancers using
      Medline (1966 to June 2004), supplemented with auto alerts and manual searches.
      Analyses are based on odds ratios for specific cancers among those ever breast
      fed compared with those never breast-fed, pooled using random-effects models.
      Forty-nine publications were potentially relevant; of these, 26 provided odds
      ratio estimates for at least one childhood cancer outcome and were included in
      metaanalyses. Overall, 92% of the studies were case-control studies, 85% relied
      on long-term recall of feeding history, only 8% examined breast-feeding
      exclusivity and control response rates were under 80% in over half. Metaanalyses
      suggested lower risks associated with having been breast-fed of 9% (95% CI = 2
      16%) for acute lymphoblastic leukemia, 24% (3-40%) for Hodgkin's disease and 41%
      (22-56%) for neuroblastoma, with little between-study heterogeneity. The
      estimates for Hodgkin's disease and neuroblastoma, however, were driven by single
      studies. There was little evidence that breast-feeding was associated with acute
      nonlymphoblastic leukemia, non-Hodgkin's lymphoma, central nervous system
      cancers, malignant germ cell tumors, juvenile bone tumors, or other solid
      cancers. In conclusion, ever having been breast-fed is inversely associated with
      acute lymphoblastic leukemia, Hodgkin's disease and neuroblastoma in childhood,
      but noncausal explanations are possible. Even if causal, the public health
      importance of these associations may be small. Our estimates suggest that
      increasing breast-feeding from 50% to 100% would prevent at most 5% of cases of
      childhood acute leukemia or lymphoma. (c) 2005 Wiley-Liss, Inc.

PMID- 15986433
TI  - Quantitative evaluation of automated skull-stripping methods applied to
      contemporary and legacy images: effects of diagnosis, bias correction, and slice
      location.
AB  - Performance of automated methods to isolate brain from nonbrain tissues in
      magnetic resonance (MR) structural images may be influenced by MR signal
      inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of
      subjects studied. The present study compared the performance of four methods:
      Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143-155);
      3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical
      College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al.
      [2004] Neuroimage 22:1060-1075; in FreeSurfer); and Brain Surface Extractor (BSE,
      Sandor and Leahy [1997] IEEE Trans Med Imag 16:41-54; Shattuck et al. [2001]
      Neuroimage 13:856-876) to manually stripped images. The methods were applied to
      uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted
      image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly
      control). To provide a criterion for outcome assessment, two experts manually
      stripped six sagittal sections for each dataset in locations where brain and
      nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard
      similarity coefficients, Hausdorff distances, and an Expectation-Maximization
      algorithm. Methods tended to perform better on contemporary datasets; bias
      correction did not significantly improve method performance. Mesial sections were
      most difficult for all methods. Although AD image sets were most difficult to
      strip, HWA and BSE were more robust across diagnostic groups compared with
      3dIntracranial and BET. With respect to specificity, BSE tended to perform best
      across all groups, whereas HWA was more sensitive than other methods. The results
      of this study may direct users towards a method appropriate to their T1-weighted
      datasets and improve the efficiency of processing for large, multisite
      neuroimaging studies.

PMID- 15986435
TI  - TP53BP2 locus is associated with gastric cancer susceptibility.
AB  - We investigated the association of the TP53BP2 locus with gastric cancer
      susceptibility in a Korean population. We assayed 9 single nucleotide
      polymorphisms (SNP) in an 82.5 kb region that included the TP53BP2 locus in 233
      male gastric cancer patients and 390 unaffected healthy male controls. The
      allelic frequencies of 4 SNP within TP53BP2, g.206692C>T, g.198267A>T,
      g.164895G>A and g.152389A>T, differed significantly between cases and controls (p
      < or = 0.0376). When compared to carriers of non-risk alleles, individuals
      homozygotic for each of the risk alleles had a 50% increase in risk of gastric
      cancer (age-adjusted odds ratio [OR] > or = 1.48; p < or = 0.0371). Furthermore,
      these 4 significantly associated SNP were in strong linkage disequilibrium (r2 >
      or = 0.51). Haplotype analysis showed that individuals with the CAGA haplotype,
      consisting of the risk alleles at each SNP, had a 1.55-fold higher risk for
      gastric cancer than individuals with the haplotype TTAT, consisting of the non
      risk alleles at each SNP (OR = 1.55; 95% confidence interval [CI] = 1.13-2.14; p
      = 0.00705). Two other SNP were not polymorphic in the study subjects, whereas the
      other 3 SNP, located toward the outside of the TP53BP2 locus, were not associated
      with gastric cancer susceptibility. Although the location of the pathogenic
      variant is not yet known, our results suggest that the TP53BP2 locus is
      associated with susceptibility to gastric cancer in the Korean population.

PMID- 15986436
TI  - Helicobacter pylori infection is associated with colon adenomatous polyps
      detected by high-resolution colonoscopy.
AB  - Helicobacter pylori (H. pylori) is associated with the development of cancer in
      the stomach, but both positive and negative associations were reported with
      colorectal neoplasia. We sought to determine whether H. pylori is associated with
      colon neoplasia in Japanese population. We examined 332 patients who underwent
      routine high-resolution total colonoscopy and serologic testing for IgG
      antibodies agonist H. pylori. Subjects who received cyclooxygenase-2 inhibitors
      or previous eradication therapy and those with borderline titer levels were
      excluded from data analysis (n = 27). Seronegative control subjects were from the
      same study population to maximize the representativeness. There were no
      significant differences in age and gender between the 2 patient groups. A
      significant increase in the incidence of adenomatous polyps (p < 0.0001) and
      decrease in normal colonoscopic findings (p < 0.0005) were observed in
      seropositive patients than those seronegative. Our study indicates an etiological
      link of H. pylori infection to colorectal neoplasia and the need of routine
      colonoscopy in seropositive patients.

PMID- 15986437
TI  - PPARgamma-dependent effects of conjugated linoleic acid on the human glioblastoma
      cell line (ADF).
AB  - Conjugated linoleic acid (CLA) has been shown to exert beneficial effects against
      carcinogenesis, atherosclerosis and diabetes. It has been demonstrated that CLA
      modulates lipid metabolism through the activation of peroxisome proliferator
      activated receptors (PPARs). The PPAR family comprises 3 closely related gene
      products, PPAR alpha, beta/delta and gamma, differing for tissue distribution,
      developmental expression and ligand specificity. It has also been demonstrated
      that activated PPARgamma results in growth inhibition and differentiation of
      transformed cells. These observations stimulated a great interest toward
      PPARgamma ligands as potential anticancer drugs to be used in a differentiation
      therapy. Glioblastomas are the most commonly diagnosed primary tumors of the
      brain in humans. The prognosis of patients with high-grade gliomas is poor and
      only marginally improved by chemotherapy. The aim of this work was to study the
      effects of CLA and of a specific synthetic PPARgamma ligand on cell growth,
      differentiation and death of a human glioblastoma cell line as well as on
      parameters responsible for the metastatic behavior of this tumor. We demonstrate
      here that CLA and PPARgamma agonist strongly inhibit cell growth and
      proliferation rate and induce apoptosis. Moreover, both treatments decrease cell
      migration and invasiveness. The results obtained show that CLA acts, directly or
      indirectly, as a PPARgamma activator, strongly suggesting that this naturally
      occurring fatty acid may be used as brain antitumor drug and as a chemopreventive
      agent. Moreover, the gamma-agonist, once experimented and validated on man, may
      represent a useful coadjuvant in glioblastoma therapy and in the prevention of
      recurrences.

PMID- 15986438
TI  - Antibodies to JC and BK viruses among persons with non-Hodgkin lymphoma.
AB  - Two related polyomaviruses, JC virus (JCV) and BK virus (BKV), commonly cause
      lifelong infections in humans, with periodic reactivation manifesting as viral
      shedding in urine. Because JCV can infect lymphocytes and cause chromosomal
      damage, it is a plausible candidate to cause non-Hodgkin lymphoma (NHL). To test
      this hypothesis, we measured IgG antibodies to JCV and BKV capsids using a virus
      like particle enzyme immunoassay in 3 separate groups of subjects. First, in a
      U.S. population-based case-control study of NHL (724 cases, 622 controls), we
      found lower JCV antibody levels in cases than controls (median optical density =
      0.12 vs. 0.21, p < 0.0001); likewise, JCV seroprevalence was lower in cases (49%
      vs. 59%, adjusted odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56
      0.87). In contrast, BKV antibody levels did not differ between groups. Second, we
      found that JCV and BKV antibody levels changed little over time among 24 NHL
      patients receiving chemotherapy. Third, we evaluated 126 homosexual men, of whom
      46 were shedding JCV and 14 were shedding BKV in urine. Antibody levels were much
      higher in shedders than non-shedders (JCV: median optical density = 0.67 vs.
      0.07, p < 0.0001; BKV: 0.87 vs. 0.40, p = 0.003), indicating that these
      antibodies are a marker for viral replication. Because no deficit of BKV antibody
      was seen in NHL cases, and because antibody levels did not change materially with
      chemotherapy, we suggest that the lower levels of JCV antibody observed in NHL
      patients may not be due entirely to a disease or treatment effect. Additional
      research is needed to determine whether JCV replication is decreased in
      individuals with NHL and whether these findings are consistent with an etiologic
      role for JCV in NHL.

PMID- 15986439
TI  - Gender difference in estrogen receptor alpha promoter hypermethylation and its
      prognostic value in non-small cell lung cancer.
AB  - It has been documented that estrogen receptor (ER) transcription silencing due to
      hypermethylation is linked to the tumor progression of breast, uterine and
      prostate cancers. Additionally, ER hypermethylation in lung tumors has been
      associated with the exposure of specific carcinogens in animal study. The role of
      hypermethylation-induced ER transcription silencing in lung tumor progression and
      its prognostic value for non-small cell lung cancer (NSCLC) patients remained
      unclear. In our study, ER hypermethylation of 123 lung tumors and adjacent normal
      parts were examined by methylation-specific PCR (MSP). Estrogen receptor mRNA
      expression in lung tumors was determined by RT-PCR. Our data indicated that ER
      hypermethylation was only detected in lung tumors, but not in adjacent normal
      lung tissues. This suggests that ER hypermethylation may be associated with lung
      tumorigenesis. Among the clinical parameters studied, only gender factor was
      correlated with ER hypermethylation with a higher frequency of ER
      hypermethylation being in male patients than in female patients (58 vs. 34%, p =
      0.01). After being stratified by gender and cigarette smoking status, a similarly
      high prevalence of ER hypermethylation was found in male smoking and nonsmoking
      patients (60 vs. 61%) as compared to that of female nonsmoking patients (34%). To
      investigate if 17-beta estradiol (E2) was responsible for such gender difference
      in ER hypermethylation, a lung cancer A549 cell with ER hypermethylation and
      without ER mRNA expression was treated with E2 of various concentrations for
      defined time intervals to show that an E2 treatment could restore the expression
      of ER mRNA and eliminate ER hypermethylation. Western blot data also showed that
      acetylated histone 3 and histone 4 of chromatin were increased significantly by
      E2 treatment. Thus, E2 can make ER mRNA re-expression by eliminating ER
      hypermethylation. To elucidate the prognostic value of ER hypermethylation,
      Kaplan-Meier analysis was carried out to show that patients with ER
      hypermethylation had a poorer prognosis than those without ER hypermethylation.
      Such prognostic prediction, however, applied only to male (p = 0.0044) patients.
      Cox regression analysis further showed the feasibility of ER hypermethylation as
      an independent prognostic factor of NSCLC (p = 0.007). It is possible that
      antiestrogens may have different therapeutic values for male and female lung
      cancer patients.

PMID- 15986440
TI  - FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent
      prostate cancer.
AB  - FTY720, a derivative of fungus, has demonstrated dramatic anticancer effect in
      several malignancies recently. Our study evaluates the therapeutic potential of
      FTY720 in the treatment of androgen-independent prostate cancer using a human
      prostate cancer xenograft in nude mice. CWR22R, an androgen-independent human
      prostate tumor xenograft was inoculated into castrated nude mice and the animals
      were administrated with either normal saline or FTY720 (10 mg/kg) through
      intraperitoneal (i.p.) injection for 20 days. Body weight and tumor volume were
      recorded every 2 days, and serum prostate specific antigen (PSA) levels were also
      measured before and after the treatment. The effect of FTY720 on tumor cell
      proliferation was examined using antibodies against PCNA and Ki-67 by
      immunohistochemical staining, MTT assay and colony forming assay, whereas
      apoptotic effect of FTY720 was evaluated by TUNEL assay and immunostaining using
      antibodies against cleaved caspase 3 and Bcl-2. In addition, the potential
      inhibitory effect of FTY720 on prostate cancer angiogenesis and metastasis was
      investigated by immunostaining of CD31, VEGF, E-cadherin and beta-catenin. Our
      results showed that FTY720 treatment led to suppression of CWR22R tumor growth
      without causing any detectable side effects in nude mice. The FTY720-induced
      tumor suppression was correlated with decreased serum PSA level as well as
      reduced proliferation rate, suppression of angiogenic factors, and restoration of
      E-cadherin and beta-catenin expression. In addition, the FTY720-treated tumors
      showed increased apoptosis rate demonstrated by increased TUNEL- and cleaved
      caspase 3-positive cells, and decreased Bcl-2 expression. Our results suggest a
      potential novel agent in the suppression of androgen-independent prostate cancer.

PMID- 15986441
TI  - Adaptation: a developmental biologist in the Antarctic.

PMID- 15986443
TI  - Hormonal contraceptive use, pregnancy and parity, and the risk of cervical
      intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal
      or mildly abnormal cytology.
AB  - Oral contraceptive (OC) use, hormonal contraceptive use and multiparity are
      potential risk factors for cervical precancer, cervical intraepithelial neoplasia
      3 (CIN3), but a limited number of studies have adequately accounted for possible
      confounding effect of oncogenic human papillomavirus (HPV) infection. To examine
      the relationships of these factors with CIN3, we conducted an analysis of women
      (n = 5,060) with minimally abnormal Pap smears who were enrolled in the ASCUS and
      LSIL Triage Study (ALTS), a clinical trial to evaluate management strategies.
      Cervical specimens collected at enrollment were tested for HPV DNA using 2
      methods. Multivariate logistics regression models were used to assess
      associations (odds ratio [OR] with 95% confidence intervals [CI]) of the
      potential risk factors (e.g., OC use and parity) with testing oncogenic HPV
      positive among controls (<CIN2) (n = 4,114) and with rigorously reviewed cases of
      CIN3 identified throughout the study (n = 499) among women with oncogenic HPV (n
      = 3,126). Only former oral contraceptive use (OR = 1.3, 95% CI = 1.0-1.7) was
      associated marginally with having an oncogenic HPV infection among controls.
      Restricted to women with oncogenic HPV, current injectable hormonal contraceptive
      users were at an elevated risk of CIN3 (OR = 1.6, 95% CI = 1.2-2.1) compared to
      women who never used them. Similarly, restricted to women with HPV16 infection,
      current users of injectable contraceptives were at a marginally elevated risk of
      CIN3 (OR = 1.5, 95% CI = 1.0-2.3) compared to women who never used them. Oral
      contraceptive use, Norplant (implantable hormonal contraceptive) use, a history
      of pregnancy, age at first pregnancy, lifetime numbers of pregnancies and
      lifetime numbers of live births were not associated with CIN3. We conclude that
      only current injectable hormonal contraceptive use slightly elevated the risk
      (approximately 50%) of CIN3 in this young and low parity population of women with
      oncogenic HPV and minimally abnormal Pap smears but further confirmation of this
      relationship is needed.

PMID- 15986444
TI  - Ribozyme-targeting reveals the rate-limiting role of pleiotrophin in
      glioblastoma.
AB  - Glioblastomas (GBMs) are the most frequent malignant brain tumors with very
      limited treatment options and nearly all GBM patients dying within 1 year.
      Pleiotrophin (PTN, HB-GAM, HBNF, OSF-1) is a secreted growth factor that shows
      mitogenic, chemotactic and transforming activity. While PTN expression is tightly
      regulated during embryogenesis and very limited in normal adult tissues, a marked
      PTN upregulation is seen in tumors including glioblastomas. Targeting of the PTN
      receptors, ALK and RPTP-zeta, indicates a contribution of PTN-activated signaling
      pathways in glioblastomas. However, the relevance of PTN expression itself is
      unknown especially since, besides PTN, at least one more growth factor, midkine
      (MK), signals through ALK and is expressed in glioblastoma. Here we demonstrate
      the biologic relevance of PTN in 2 glioblastoma cell lines in vitro and in vivo.
      We show that stable ribozyme-targeting leads to a robust reduction of PTN mRNA
      and protein levels. This results in decreased cell proliferation, cell migration
      and soft agar colony formation in vitro. Comparing clonal ribozyme-transfected
      cells with different residual PTN levels, we establish a PTN gene-dose effect of
      glioblastoma cell proliferation. In a subcutaneous tumor xenograft mouse model,
      in vivo growth is markedly reduced upon PTN depletion, which is paralleled by
      decreased PTN serum levels. Furthermore, the immunohistochemical analysis of the
      tumors shows reduced angiogenesis in PTN-depleted tumors. We conclude that PTN is
      a rate-limiting growth factor in glioblastoma. Since PTN is overexpressed in
      glioblastomas but rarely found in normal tissue, PTN may represent an attractive
      therapeutic target.

PMID- 15986442
TI  - Survivin expression by metastatic melanoma predicts poor disease outcome in
      patients receiving adjuvant polyvalent vaccine.
AB  - Survivin and livin are members of the inhibitor of apoptosis protein (IAP)
      family. We hypothesized that elevated expression levels of these 2 IAP genes in
      resected advanced-stage metastatic melanoma lesions would be associated with poor
      disease outcome in patients receiving a polyvalent therapeutic cancer vaccine
      (Canvaxintrade mark). A quantitative real-time RT-PCR (qRT) assay for survivin
      and livin genes was used to assess mRNA expression in 63 metastatic melanomas
      obtained during cytoreductive surgery of American Joint Committee on Cancer
      (AJCC) stage IV melanoma. Nineteen of 63 metastatic melanoma patients received
      Canvaxin pre- and postoperatively, and 37 patients received only postoperative
      Canvaxin. Expression of survivin and livin protein was assessed by
      immunohistochemistry (IHC) and then correlated with mRNA. Survivin mRNA was
      detected in 62 of 63 (98%) melanoma specimens ranging from 0-5.96 x 10(4) mRNA
      copies of total RNA. Lower mRNA copy levels of survivin significantly correlated
      with improved overall survival among the 37 patients who received Canvaxin
      postoperatively but not preoperatively (log-rank test, p = 0.023). Among patients
      with low survivin mRNA copies, those who received postoperative Canvaxin did
      significantly better than patients who received pre- and postoperative Canvaxin
      (p = 0.003). Livin mRNA was detectable in 60 of 63 (95%) metastatic melanoma
      specimens but had no significant prognostic utility. These studies demonstrate
      that lower levels of survivin in recurrent metastatic melanomas are associated
      with significantly improved survival in patients receiving postoperative adjuvant
      immunotherapy. Overall, the study indicates survivin expression in metastatic
      melanomas can significantly influence disease outcome and patient responses to
      immunotherapy.

PMID- 15986445
TI  - Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation
      carriers.
AB  - Early age at first birth and multiparity have been associated with a decrease in
      the risk of breast cancer in women in the general population. We examined whether
      this relationship is also present in women at high risk of breast cancer due to
      the presence of a mutation in either of the 2 breast cancer susceptibility genes,
      BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women
      with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and
      Israel. Women who had been diagnosed with breast cancer were matched with
      unaffected control subjects for year of birth, country of residence, and mutation
      (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their
      reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      derived by conditional logistic regression. Among BRCA1 carriers, parity per se
      was not associated with the risk of breast cancer (OR for parous vs. nulliparous
      = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4
      or more children had a 38% decrease in breast cancer risk compared to nulliparous
      women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers,
      increasing parity was associated with an increased risk of breast cancer; women
      with 2 or more children were at approximately 1.5 times the risk of breast cancer
      as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with
      BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast
      cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01
      1.36; p = 0.03). There was no significant increase in the risk of breast cancer
      among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI =
      0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast
      cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls
      (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast
      cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past
      (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was
      observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers,
      increasing parity was associated with a significant increase in the risk of
      breast cancer before age 50 and this increase was greatest in the 2-year period
      following a pregnancy.

PMID- 15986446
TI  - Biallelic somatic inactivation of the NF1 gene through chromosomal translocations
      in a sporadic neurofibroma.
AB  - Neurofibroma is a benign tumor originating from Schwann cells in peripheral nerve
      sheaths and may occur as a sporadic tumor or as part of the dominantly inherited
      tumor syndrome NF1. NF1 is caused by constitutional mutations in the NF1 gene,
      located in chromosome band 17q11. Whereas the involvement of the NF1 gene in
      neurofibroma development in NF1 patients has been fairly well characterized, the
      significance of inactivation of this gene in sporadic neurofibromas remains less
      well investigated. Inactivation of both copies of NF1 has been described in a few
      neurofibromas from NF1 patients, and LOH at the same locus has been reported in
      additional cases. In the present study, we report the cytogenetic and molecular
      cytogenetic findings in a sporadic neurofibroma that at G-banding analysis showed
      a translocation between one chromosome 2 and the long arms of both copies of
      chromosome 17. FISH analysis using a set of 3 BAC clones covering the entire
      coding region of NF1 revealed the complete loss of one allele and the deletion of
      the 5' portion of the second allele as a result of 2 translocation events. To the
      best of our knowledge, this represents the first demonstration of a somatic
      biallelic inactivation of the NF1 gene in neurofibroma, providing further
      evidence for the importance of NF1 inactivation also in sporadic neurofibromas.

PMID- 15986447
TI  - Characterization of Hap/BAG-1 variants as RP1 binding proteins with antiapoptotic
      activity.
AB  - The MAPRE protein family (EB1, RP1, EB2) represents a highly conserved group of
      proteins that localize preferentially to the plus end of microtubules, both in
      the nucleus and cytoplasm. In addition, MAPRE family members are characterized by
      their capability to bind to the C-terminus of the adenomatous polyposis coli
      (APC) protein and tubulin in order to stabilize microtubules. Apart from the
      interaction with APC and tubulin, no other direct binding partners are known
      today. Because the RP1 gene product was identified in activated T cells, we set
      out to search for new interacting molecules in a yeast 2-hybrid system. We
      isolated a cDNA variant encoding for the antiapoptotic Hap/BAG-1 protein
      truncated by 34 amino acids at the C-terminus. In the original Hap/BAG-1 protein,
      the C-terminal domain is responsible for binding to Bcl-2 and Hsp/Hsc70, which is
      believed to be the reason for its antiapoptotic activity. Although this putative
      Hap/BAG-1 variant protein showed no interaction with Bcl-2 or Hsp/Hsc70, it was
      perfectly able to confer resistance to apoptosis. Subcellular distribution
      analysis revealed that the Hap/Bag-1 variant protein localized homogenously to
      the cytoplasm and shuttles into the nucleus in response to stress, a process that
      could be blocked by RP1 protein overexpression.

PMID- 15986448
TI  - High-throughput tissue microarray analysis of CMYC amplificationin urinary
      bladder cancer.
AB  - Alterations of chromosome 8, preferentially deletions of 8p and gains of 8q,
      belong to the most frequent cytogenetic changes in bladder cancer. CMYC on 8q24
      is a candidate oncogene in this region. Little is known about the clinical
      significance of CMYC copy number changes in urinary bladder cancer because its
      frequency is low and a limited numbers of tumors were analyzed so far. To
      investigate the impact of CMYC alterations on tumor progression and patient
      prognosis in bladder cancer, we applied FISH to a tissue microarray containing
      2317 bladder cancer samples. Presence of CMYC copy number increase was associated
      with advanced stage and high grade. CMYC amplifications were seen in 3 of 467 pTa
      (0.6%), 10 of 247 pT1 (4%) and 11 of 201 pT2-4 urothelial carcinomas (5.5%; p <
      0.0001), as well as in 1 of 123 G1 (0.8%), 8 of 470 G2 (1.7%) and 17 of 365 G3
      urothelial carcinomas (4.7%; p < 0.0001). CMYC gains were present in 49 of 467
      pTa (10.5%), 39 of 247 pT1 (15.8%) and 43 of 201 pT2-4 urothelial carcinoma
      (21.4%; p < 0.0001), as well as in 7 of 123 G1 (5.7%), 56 of 470 G2 (11.9%) and
      72 of 365 G3 urothelial carcinomas (19.7%; p < 0.0001). CMYC copy number changes
      were unrelated to prognosis of bladder cancer patients. We conclude that
      alterations of the CMYC gene, including copy number gains and amplifications, are
      linked to genetically unstable bladder cancers that are characterized by a high
      histologic grade and/or invasive growth. Patient prognosis was not affected by
      CMYC gene copy number changes.

PMID- 15986449
TI  - Stages of embryonic development in the amphipod crustacean, Parhyale hawaiensis.
AB  - Studying the relationship between development and evolution and its role in the
      generation of biological diversity has been reinvigorated by new techniques in
      genetics and molecular biology. However, exploiting these techniques to examine
      the evolution of development requires that a great deal of detail be known
      regarding the embryonic development of multiple species studied in a phylogenetic
      context. Crustaceans are an enormously successful group of arthropods and extant
      species demonstrate a wide diversity of morphologies and life histories. One of
      the most speciose orders within the Crustacea is the Amphipoda. The embryonic
      development of a new crustacean model system, the amphipod Parhyale hawaiensis,
      is described in a series of discrete stages easily identified by examination of
      living animals and the use of commonly available molecular markers on fixed
      specimens. Complete embryogenesis occurs in 250 h at 26 degrees C and has been
      divided into 30 stages. This staging data will facilitate comparative analyses of
      embryonic development among crustaceans in particular, as well as between
      different arthropod groups. In addition, several aspects of Parhyale embryonic
      development make this species particularly suitable for a broad range of
      experimental manipulations.

PMID- 15986450
TI  - Expression levels of the putative zinc transporter LIV-1 are associated with a
      better outcome of breast cancer patients.
AB  - We investigated the expression pattern of the breast cancer associated gene LIV-1
      on mRNA and protein level in 111 human breast cancer patients by in situ
      hybridization as well as immunohistochemistry and focused on the unknown
      potential of LIV-1 expression levels as a prognostic marker. To our knowledge,
      this is the first study on endogenous LIV-1 protein expression. Results of our
      study indicate that LIV-1 mRNA and protein expression levels are only weakly
      correlated, suggesting posttranscriptional regulatory mechanisms. Furthermore,
      LIV-1 mRNA quantity in combination with a positive ER status seem to represent a
      better marker than the progesterone receptor status according to the prognostic
      significance for relapse free survival (RFS). A negative correlation of LIV-1
      protein levels with tumor size, grade and stage reflects an association of LIV-1
      protein expression with less aggressive tumors. High LIV-1 protein expression
      seems to be associated with a longer relapse free and overall survival in breast
      cancer patients with invasive ductal carcinoma. This association, however, seems
      to be dependent from other prognostic markers. Our data suggest that LIV-1 is a
      promising candidate for a novel marker for breast cancer patients with better
      outcome. Furthermore, our study presents a revised cDNA sequence of LIV-1 and
      demonstrates the localization of endogenous LIV-1 in the endoplasmic reticulum.

PMID- 15986451
TI  - Control of planar cell polarity by interaction of DWnt4 and four-jointed.
AB  - The Drosophila eye and the wing display specific planar cell polarity. Although
      Frizzled (Fz) signaling has been implicated in the establishment of ommatidial
      and wing hair polarity, evidence for the Wnt gene function has been limited. Here
      we examined the function of a Drosophila homolog of Wnt4 (DWnt4) in the control
      of planar polarity. We show that DWnt4 mRNA and protein are preferentially
      expressed in the ventral region of eye disc. DWnt4 mutant eyes show polarity
      reversals mostly in the ventral domain, consistent with the ventral expression of
      DWnt4. Ectopic expression of DWnt4 in the dorsoventral (DV) polar margins is
      insufficient to induce ommatidial polarity but becomes inductive when coexpressed
      with Four-jointed (Fj). Similarly, DWnt4 and Fj result in synergistic induction
      of hair polarity toward the source of expression in the wing. Consistent with
      genetic interaction, we provide evidence for direct interaction of DWnt4 and Fj
      transmembrane protein. The extracellular domain of Fj is required for direct
      binding to DWnt4 and for the induction of hair polarity. In contrast to the
      synergy between DWnt4 and Fj, DWnt4 antagonizes the polarizing effect of Fz. Our
      results suggest that DWnt4 is involved in ommatidial polarity signaling in the
      ventral region of the eye and its function is mediated by interacting with Fj.

PMID- 15986452
TI  - Reference guide to the stages of chick heart embryology.
AB  - Cardiac progenitors of the splanchnic mesoderm (primary and secondary heart
      field), cardiac neural crest, and the proepicardium are the major embryonic
      contributors to chick heart development. Their contribution to cardiac
      development occurs with precise timing and regulation during such processes as
      primary heart tube fusion, cardiac looping and accretion, cardiac septation, and
      the development of the coronary vasculature. Heart development is even more
      complex if one follows the development of the cardiac innervation, cardiac
      pacemaking and conduction system, endocardial cushions, valves, and even the
      importance of apoptosis for proper cardiac formation. This review is meant to
      provide a reference guide (Table 1) on the developmental timing according to the
      staging of Hamburger and Hamilton (1951) (HH) of these important topics in heart
      development for those individuals new to a chick heart research laboratory. Even
      individuals outside of the heart field, who are working on a gene that is also
      expressed in the heart, will gain information on what to look for during chick
      heart development. This reference guide provides complete and easy reference to
      the stages involved in heart development, as well as a global perspective of how
      these cardiac developmental events overlap temporally and spatially, making it a
      good bench top companion to the many recently written in-depth cardiac reviews of
      the molecular aspects of cardiac development.

PMID- 15986453
TI  - Complex colony-level organization of the deep-sea siphonophore Bargmannia
      elongata (Cnidaria, Hydrozoa) is directionally asymmetric and arises by the
      subdivision of pro-buds.
AB  - Siphonophores are free-swimming colonial hydrozoans (Cnidaria) composed of
      asexually produced multicellular zooids. These zooids, which are homologous to
      solitary animals, are functionally specialized and arranged in complex species
      specific patterns. The coloniality of siphonophores provides an opportunity to
      study the major transitions in evolution that give rise to new levels of
      biological organization, but siphonophores are poorly known because they are
      fragile and live in the open ocean. The organization and development of the deep
      sea siphonophore Bargmannia elongata is described here using specimens collected
      with a remotely operated underwater vehicle. Each bud gives rise to a precise,
      directionally asymmetric sequence of zooids through a stereotypical series of
      subdivisions, rather than to a single zooid as in most other hydrozoans. This
      initial description of development in a deep-sea siphonophore provides an example
      of how precise colony-level organization can arise, and illustrates that the
      morphological complexity of cnidarians is greater than is often assumed.

PMID- 15986454
TI  - Magnetic resonance profiling of human skin in vivo using GARField magnets.
AB  - It is shown that one-dimensional magnetic resonance imaging (MRI-profiling) of
      human forearm and side-of-hand skin in vivo is possible using GARField magnets.
      Strong profile contrast originating from differing molecular mobility is seen for
      stratum corneum and viable epidermis. The first in vivo spatially-resolved field
      gradient measurements of water self-diffusivity, D, in the stratum corneum (2.0 x
      10(-6) cm(2)/s) and viable epidermis (8.5 x 10(-6) cm(2)/s) are reported. Also
      reported are spatially resolved measurements of the (1)H spin-lattice relaxation
      time, T(1), the spin-spin relaxation time, T(2). It is further shown that the
      application of moisturizing agents to the skin noticeably affects the profiles.
      However, universal behavior is not seen as both signal increases and decreases
      are observed dependent on agent and volunteer.

PMID- 15986456
TI  - Role of actin polymerization in bending of the early heart tube.
AB  - During cardiac c-looping, the heart transforms from a straight tube into a c
      shaped tube, presenting the first evidence of left-right asymmetry in the embryo.
      C-looping consists of two primary deformation components: ventral bending and
      dextral rotation. This study examines the role of actin polymerization in bending
      of the heart tube. Exposure of stage 9-11 chick embryos to low concentrations of
      the actin polymerization inhibitors cytochalasin D (5 nM-2.0 microM) and
      latrunculin A (LA; 25 nM-2.0 microM) suppressed looping in a stage- and
      concentration-dependent manner in both whole embryos and isolated hearts. Local
      exposure of either the dorsal or ventral sides of isolated hearts to LA also
      inhibited looping, but less than global exposure, indicating that both sides
      contribute to the bending mechanism. Taken together, these data suggest that
      ongoing actin polymerization is required for the bending component of cardiac c
      looping, and we speculate that polymerization-driven myocardial cell shape
      changes cause this deformation.

PMID- 15986457
TI  - Enhanced absorption of 3-O-methyl glucose following gastrointestinal injury
      induced by repeated oral administration of 5-FU in mice.
AB  - The absorption of nutrients is mainly mediated by specific carriers and generally
      retarded following gastrointestinal injury. The aim of this study was to assess
      the effect of repeated oral administration of 5-fluorouracil (5-FU) on the
      intestinal absorption of glucose by using 3-O-methyl-D-glucose (3-OMG), a glucose
      analogue that is not metabolized, as a probe. Repeated administration of 5-FU (60
      mg/kg/day for 3 days) readily induced intestinal mucosal injury assessed by
      visual observation and loss of intestinal wet weight. At the same time, the
      carrier-dependent absorption clearance of 3-OMG was increased 1.8-fold, while the
      carrier-independent absorption assessed by L-glucose transport was not affected.
      Phloretin, a glucose transporter 2 (GLUT2) inhibitor, completely abolished the
      absorption of 3-OMG in both control and 5-FU-treated mice, indicating the
      specific effect on the carrier-dependent process. Protein and mRNA expressions of
      GLUT2 were significantly higher in 5-FU-treated mice compared to the control
      mice. Sodium (Na(+)) glucose co-transporter 1 (SGLT1) expressions were also
      moderately elevated in 5-FU-treated mice. Concomitantly, the uptake of D-glucose
      into both isolated brush border and basolateral membrane vesicles was
      significantly increased. These results indicate that repeated oral administration
      of 5-FU did not hamper, but unexpectedly induced, SGLT1 and GLUT2 expression to
      enhance glucose absorption.

PMID- 15986455
TI  - Using a histone yellow fluorescent protein fusion for tagging and tracking
      endothelial cells in ES cells and mice.
AB  - We report the first endothelial lineage-specific transgenic mouse allowing live
      imaging at subcellular resolution. We generated an H2B-EYFP fusion protein which
      can be used for fluorescent labeling of nucleosomes and used it to specifically
      label endothelial cells in mice and in differentiating embryonic stem (ES) cells.
      A fusion cDNA encoding a human histone H2B tagged at its C-terminus with enhanced
      yellow fluorescent protein (EYFP) was expressed under the control of an Flk1
      promoter and intronic enhancer. The Flk1::H2B-EYFP transgenic mice are viable and
      high levels of chromatin-localized reporter expression are maintained in
      endothelial cells of developing embryos and in adult animals upon breeding. The
      onset of fluorescence in differentiating ES cells and in embryos corresponds with
      the beginning of endothelial cell specification. These transgenic lines permit
      real-time imaging in normal and pathological vasculogenesis and angiogenesis to
      track individual cells and mitotic events at a level of detail that is
      unprecedented in the mouse.

PMID- 15986458
TI  - Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type
      systems intended for topical application.
AB  - Aminolevulinic acid (ALA) stability within topical formulations intended for
      photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5
      dipropionic acid (PY). Most strategies to improve stability use low pH vehicles,
      which can cause cutaneous irritancy. To overcome this problem, a novel approach
      is investigated that uses a non-aqueous vehicle to retard proton-induced charge
      separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that
      leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on
      methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or
      glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell
      below pharmaceutically acceptable levels after 6 months, with bioadhesive patches
      stored at 5 degrees C demonstrating the best stability by maintaining 86.2% of
      their original loading. Glycerol-based gels maintained 40.2% in similar
      conditions. However, ALA loss did not correspond to expected increases in PY,
      indicating the presence of another degradative process that prevented
      dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in
      respect of the mechanism observed in the patch system, but showed clearly that an
      esterification reaction involving ALA and both glycerol and poly(ethyleneglycol)
      was occurring. This was especially marked in the glycerol gels, where only 2.21%
      of the total expected PY was detected after 204 days at 5 degrees C. Non-specific
      esterase hydrolysis demonstrated that ALA was recoverable from the gel systems,
      further supporting esterified binding within the gel matrices. It is conceivable
      that skin esterases could duplicate this finding upon topical application of the
      gel and convert these derivatives back to ALA in situ, provided skin penetration
      is not affected adversely.

PMID- 15986459
TI  - Effect of the covalent modification of horseradish peroxidase with poly(ethylene
      glycol) on the activity and stability upon encapsulation in polyester
      microspheres.
AB  - Encapsulation of proteins in polyester microspheres by coacervation methods
      frequently causes protein inactivation and aggregation. Furthermore, an often
      substantial amount of the encapsulated proteins is released within the first 24 h
      from the microspheres. To overcome these problems poly(ethylene glycol) (PEG) was
      employed as excipient and protein-modifying agent. The model protein horseradish
      peroxidase (HRP) was chemically modified or co-lyophilized with PEG of differing
      molecular weights, namely PEG(5000), PEG(20000), and PEG(40000). The lyophilized
      preparations were encapsulated in poly(D,L-lactide-co-glycolic) acid (PLGA)
      microspheres by a coacervation method. Covalent modification of HRP with PEG
      increased the encapsulation efficiency (EE) from 83% to about 100% while PEG when
      used as an excipient reduced the EE. Encapsulation caused aggregation of ca. 5%
      of non-modified HRP and the residual specific activity was only 57%. Covalent
      modification with PEG reduced HRP aggregation to less than 1% and improved its
      residual activity to more than 95%. When PEG was used as excipient similar
      results were found with respect to a reduction in encapsulation-induced
      aggregation, but no more than 80% of residual activity was obtained even for the
      best formulation after encapsulation. It was also found that covalent
      modification of HRP with PEG substantially reduced the unwanted initial "burst"
      release observed during the initial 24 h of in vitro release from about 70% to
      23%. Furthermore, HRP activity and stability were also improved during in vitro
      release for HRP-PEG conjugates. The data show that covalent modification of
      proteins with PEG might be useful to improve protein stability during
      coacervation encapsulation and subsequent release as well as to increase EE and
      reduce the burst release.

PMID- 15986460
TI  - Bioavailability of seocalcitol I: Relating solubility in biorelevant media with
      oral bioavailability in rats--effect of medium and long chain triglycerides.
AB  - Simulated intestinal media (SIM) containing bile salt (BS) and phospholipids (PL)
      with and without medium chain lipolytic products (MC-LP) or long chain lipolytic
      products (LC-LP) were developed to study the solubility of seocalcitol. Both MC
      LP and LC-LP were studied in order to investigate the influence of fatty acid
      chain length on the in vitro solubility of seocalcitol. The same solubility of
      seocalcitol was found in media containing either MC-LP or LC-LP. The
      bioavailability after oral administration of seocalcitol dissolved in medium
      chain triglyceride (MCT), long chain triglyceride (LCT), and a reference
      formulation containing propylene glycol (PG) was studied in vivo in rats. The
      lipid formulations showed a twofold increase in bioavailability compared with the
      reference formulation, indicating positive effects of lipids on the
      bioavailability reflecting a better solubility in the intestine and protection
      against precipitation of seocalcitol in the gastro intestinal tract. There was no
      difference in the in vivo bioavailability of seocalcitol between the MCT and the
      LCT solutions, which correlates with the identical in vitro solubility of
      seocalcitol in SIM containing MC-LP or LC-LP.

PMID- 15986461
TI  - Intracellular delivery of doxorubicin with RGD-modified sterically stabilized
      liposomes for an improved antitumor efficacy: in vitro and in vivo.
AB  - Passive targeting by sterically stabilized liposomes (SSL), once combined with
      efficient intracellular delivery, may be a very useful strategy to improve the
      antitumor efficacy for the anticancer agents. The arginine-glycine-aspartic acid
      tripeptide (RGD) is known to serve as a recognition motif for several different
      integrins located on cell surface. In this study, the RGD tripeptide was coupled
      to the distal end of the poly (ethylene glycol)-coated liposomes (RGD-SSL) aimed
      to achieve increased tumor accumulation and enhanced intracellular uptake. DOX
      loaded RGD-SSL (RGD-SSL-DOX), DOX-loaded SSL (SSL-DOX), and free DOX were
      compared with respect to their in vitro uptake and cytotoxicity and their in vivo
      biodistribution and therapeutic efficacy in tumor-bearing mice. Flow cytometry
      and confocal microscopy studies revealed that RGD-SSL could facilitate the DOX
      uptake into melanoma cells by integrin-mediated endocytosis. RGD-SSL-DOX
      displayed higher cytotoxicity on melanoma cells than SSL-DOX. While RGD-SSL-DOX
      demonstrated prolonged circulation time and increased tumor accumulation as SSL
      DOX did, it showed remarkably higher splenic uptake than SSL-DOX. Mice receiving
      RGD-SSL-DOX (5 mg DOX/kg) showed effective retardation in tumor growth compared
      with those receiving same dose of SSL-DOX, free DOX solution, or saline. These
      results suggest that RGD-modified SSL may be a feasible intracellular targeting
      carrier for efficient delivery of chemotherapeutic agents into tumor cells.

PMID- 15986462
TI  - Effect of formulation factors on electroosmotic glucose transport through human
      skin in vivo.
AB  - Glucose transport through human skin can be facilitated by electroosmotic flow
      that results from the application of an electric current across the skin
      (iontophoresis). A series of studies on human volunteers examined how formulation
      factors (buffer type, pH, ionic strength, and buffer concentration) affect the
      amount of glucose extracted from interstitial fluid through the skin. Sampling
      cells were placed on subjects' forearms and a current of 0.25 mA/cm(2) was passed
      across the skin for 5 h. Samples were collected every 20 min and analyzed for
      glucose concentration. Two methods were used. In one method, subjects ingested
      glucose and one formulation was tested in each pair of sampling cells for the
      study duration. The ratio of transdermal glucose flux to blood glucose was
      determined and compared across formulations. In another method, subjects fasted
      through the study, and different formulations were sequentially tested in each
      sampling cell. Citrate was found to give higher flux than bicarbonate or
      phosphate buffers. Transport increased with increasing pH from 4.5 to 6.5 for
      citrate buffer and 6.5 to 7.5 for bicarbonate buffer. Increased salt
      concentration in the formulation decreased transport. Increased phosphate
      concentration increased transport. These results can be used to optimize
      electroosmotic transport through the skin.

PMID- 15986463
TI  - Increased erythrocyte distribution of valproic acid in pharmacokinetic
      interaction with carbapenem antibiotics in rat and human.
AB  - Carbapenem antibiotics cause pharmacokinetic interaction with valproic acid (VPA)
      in clinical pharmacotherapy. Here, we investigated the mechanism of interaction
      from the viewpoint of erythrocyte distribution of VPA in rats and humans.
      Imipenem or panipenem was administered intravenously and then VPA intravenously
      or into the intestinal lumen in rats. Both imipenem and panipenem significantly
      decreased plasma VPA levels. In contrast, these antibiotics did not affect, or
      rather increased, VPA levels in whole blood, and increased the erythrocyte
      distribution of VPA in vivo. In clinical, two patients receiving VPA were given
      imipenem intravenously, because of intractable infectious diseases. Imipenem
      lowered plasma VPA levels by approximately 40%-60% of original levels, and
      increased the erythrocyte distribution of VPA, as observed in rats. In
      conclusion, the pharmacokinetic interaction between VPA and carbapenem
      antibiotics, in which plasma VPA levels were markedly reduced, may partly be
      derived from the increased erythrocyte distribution of VPA.

PMID- 15986464
TI  - Development of a novel high-concentration galantamine formulation suitable for
      intranasal delivery.
AB  - The goal of the current study was to develop an intranasal (IN) formulation of
      the acetylcholinesterase inhibitor galantamine, an important therapeutic for
      treating Alzheimer's disease. To allow for delivering a therapeutically relevant
      dose, it was necessary to greatly enhance drug solubility. Various approaches
      were examined to this end, including adding co-solvents, cyclodextrins, and
      counterion exchange. Of these, the latter, for example, replacement of bromide
      ion with lactate or gluconate, resulted in a dramatic drug solubility increase,
      more than 12-fold. NMR confirmed the molecular structure of new drug salt forms.
      An in vitro epithelial tissue model was used to assess drug permeability and
      cellular toxicity. In vitro, galantamine lactate formulations performed as well
      as or better than their hydrobromide (HBr) counterparts with respect to drug
      permeation across the epithelial membrane with minimal toxicity. In vivo studies
      in rats compared pharmacokinetic (PK) profiles of different formulations. The in
      vivo studies confirmed that IN galantamine achieves systemic blood levels
      comparable to those of conventional oral administration. Both the in vitro and in
      vivo data support the feasibility of IN administration of this important drug.

PMID- 15986465
TI  - Effects of sucrose and mannitol on asparagine deamidation rates of model peptides
      in solution and in the solid state.
AB  - Asparagine (Asn) degradation kinetics in two model peptides, Gly-Gln-Asn-Gly-Gly
      (GQNGG) and Val-Tyr-Pro-Asn-Gly-Ala (VYPNGA), were studied at 50 degrees C in pH
      7 buffer solutions in the presence and absence of 5% (w/v) sucrose or mannitol
      and at 50 degrees C and 30% relative humidity in solid samples lyophilized from
      these solutions. Solid formulations were characterized using Karl Fischer
      coulometric titration, thermal gravimetric analysis (TGA), differential scanning
      calorimetry (DSC), Fourier-transform infrared spectrometry (FTIR), and solid
      state nuclear magnetic resonance (NMR) spectroscopy. GQNGG and VYPNGA showed
      similar pseudo first-order deamidation rates in solution in the absence of
      sucrose and mannitol. Adding 5% sucrose or mannitol decreased the rates by no
      more than 17%. The model peptides degraded 2- to 80-fold more slowly in the solid
      formulations of sucrose and mannitol than in 5% solutions of these carbohydrates.
      Ratios of deamidation rates of the model peptides depended upon the solid matrix.
      In the mannitol solid, the ratio of deamidation rates of GQNGG and VYPNGA
      (GQNGG:VYPNGA) was approximately 8, while in the sucrose solid, the model
      peptides deamidated at similar rates (GQNGG:VYPNGA congruent with 1). DSC showed
      the mannitol formulations to be largely amorphous immediately after
      lyophilization with some ordered, crystalline-like structure; the extent of
      ordered structure increased during storage as shown by FTIR and ssNMR. In
      contrast, the sucrose formulation was largely amorphous after lyophilization and
      remained so during storage. Together, the results showed that 5% sucrose or
      mannitol in solution does not significantly change the rates of Asn deamidation
      of the model peptides, while sucrose stabilizes the model peptides against
      deamidation more than mannitol in the solid state.

PMID- 15986466
TI  - Postfabrication encapsulation of model protein drugs in a negatively
      thermosensitive hydrogel.
AB  - A postfabrication encapsulation technique was developed for loading model protein
      drugs into an intelligent and biodegradable hydrogel film, which exhibits
      negative thermosensitivity with a desirable phase transition temperature between
      refrigerator temperature and body temperature. The hydrogel comprises mainly
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer,
      and oligo(lactide). The model proteins Hemoglobin and Bovine Serum Albumin were
      loaded into the hydrogel films by soaking the gels at 4 degrees C, at which the
      hydrogel film was swollen. The loaded drug was released gradually in PBS at 37
      degrees C, where the hydrogel film was shrunken. Because the hydrogel is
      biodegradable, the loaded drug could be released completely. It is confirmed that
      proteins can, in their native structures, be included in the hydrogel via the
      present technique, as characterized by FTIR, Raman spectrum, UV/VIS spectrum, and
      circular dichroism spectrum. The highlight of our approach is avoidance of high
      temperatures and organic solvents in encapsulation, making it ideal for protein
      drug delivery systems.

PMID- 15986467
TI  - Prediction of in vivo intestinal absorption enhancement on P-glycoprotein
      inhibition, from rat in situ permeability.
AB  - The purpose of this study is to determine the functional role of P-glycoprotein
      (P-gp) in intestinal absorption of drugs and to quantitatively predict the in
      vivo absorption enhancement on P-gp inhibition. In situ single-pass rat ileum
      permeability and aqueous solubility were measured for a set of 16 compounds.
      Permeability studies were also carried out in the presence of P-gp inhibitor to
      estimate the permeability enhancement on P-gp inhibition. A significant
      correlation was obtained between rat ileum permeability and the literature human
      intestinal absorption (HIA), F(a,human) (r = 0.891; p < 0.01). Compounds with
      permeability >0.2 x 10(-4) cm/s are completely absorbed; however, few practically
      insoluble compounds were overestimated with this relationship. Inhibition of P-gp
      increased the permeability (p < 0.05) of three moderately and three highly
      permeable compounds. Efflux inhibition ratio (EIR), the ratio of permeability due
      to P-gp-mediated efflux activity and passive permeability only, for these
      compounds was in the order of digoxin > paclitaxel > fexofenadine > quinidine >
      verapamil > cyclosporine. Integration of EIR with permeability versus F(a,human)
      predicted that modulation of P-gp has no significant effect on the absorption of
      highly permeable compounds (quinidine, verapamil, and cyclosporine A), while for
      moderately permeable compounds (digoxin, paclitaxel, and fexofenadine), P-gp
      profoundly influences the intestinal permeability. The in situ permeability in
      rat ileum may be used to predict the in vivo P-gp function and its quantitative
      contribution to intestinal drug absorption. Integration of the functional
      activity of P-gp with the characteristics of BCS may explain drug interactions
      and explore the possible pharmacokinetic advantage on P-gp inhibition.

PMID- 15986468
TI  - Bilayer to micelle transition of DMPC and alcohol ethoxylate surfactants as
      studied by isoperibol calorimetry.
AB  - The interaction of dimyristoylphosphatidylcholine (DMPC) with non-ionic
      surfactants has been studied using isoperibol calorimetry. Phospholipid
      surfactant systems were formed in the isoperibol calorimeter with varying amounts
      of surfactant and the change in enthalpy on formation was measured.
      Solubilization of the phospholipid lamellae was assessed as a decrease in the
      enthalpy of reaction of co-films containing DMPC and increasing amounts of three
      linear alcohol ethoxylate surfactants: C(10)H(21)(OCH(2)CH(2))(3)OH,
      C(10)H(21)(OCH(2)CH(2))(5)OH, or C(12)H(25)(OCH(2)CH(2))(7)OH. The isoperibol
      calorimetry data for DMPC/surfactant/water systems were consistent with a
      theoretical three-stage model for the solubilization of phospholipids by
      surfactants, whereby phospholipid bilayers are transformed into mixed micelles
      with increasing amounts of surfactant. The results indicate that: (i) the
      interaction between phospholipid and surfactants results in a non-linear
      correlation between the enthalpy of reaction and the surfactant concentration;
      (ii) the structural stage of the lamellar to micelle transition (mixed bilayers,
      mixed micelles, or both) can be determined from calorimetric data; (iii) phase
      boundaries in the solubilization process (bilayer saturation, micelle saturation)
      can be identified as break points in the enthalpy-concentration curve; and (iv)
      increasing the hydrophilicity of the surfactant results in a decrease of the
      surfactant concentration producing the onset of solubilization.

PMID- 15986469
TI  - Effect of ion-exchange fiber structure on the binding and release of model
      salicylates.
AB  - Salicylates were used as model anions to evaluate the effect of the structure
      (framework and ion-exchange groups) of fibrous anion-exchangers on the extent and
      mechanism(s) of compound binding and release. Binding was affected by the
      physicochemical properties of both the salicylates and the ion-exchange fibers.
      The highest molar amount of binding was obtained with the most lipophilic
      salicylate (5-chlorosalicylic acid) and the weak base (vinylpyridine) anion
      exchange fibers. However, when the ion-exchange capacity was taken into account,
      higher binding was obtained in fibers of poly(ethylene) framework compared to the
      viscose-based fibers. The extent of salicylate release into NaCl solution(s) was
      dependent on the physicochemical characteristics of both the fiber and the bound
      model salicylate as well as on the amount of extracting ions. With strong base
      fibers (trimethylammonium), the viscose framework released the salicylates more
      efficiently than the poly(ethylene) framework. In the case of weak base fibers,
      the poly(ethylene) framework released the salicylates to a higher extent than the
      viscose framework. Calculated equilibrium constants (K) of the ion-exchange
      reactions illustrated that in addition to electrostatic interactions (pure ion
      exchange mechanism), non-electrostatic interactions (hydrophobic interactions
      and/or hydrogen bonding) were also involved. However, the release of the
      salicylates was efficiently modified by the amount of extracting electrolyte,
      demonstrating that ion-exchange was the prevalent release mechanism.

PMID- 15986471
TI  - Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid.
AB  - This study describes the formation of cationic, cage-like complexes which have a
      structure similar to classic anionic ISCOMs. In order to prepare these complexes
      cholesterol, a major component of classic ISCOM formulations, was substituted
      with a cationic derivative, 3beta-[N-(N',N'-dimethylaminoethane)-carbamoyl]
      cholesterol (DC-CHOL). Colloidal dispersions with varying compositions of DC
      CHOL, phosphatidylcholine, and Quil-A, which is a mixture of anionic triterpene
      saponins, were prepared by the lipid-film hydration method and characterised by
      transmission electron microscopy and laser Doppler electrophoresis. The colloidal
      structures obtained are presented in pseudo-ternary phase diagrams with two
      buffer systems as the pseudo-component. It was found that the formation of
      cationic, cage-like particles is highly depending on the formulation buffer. With
      TRIS buffered saline (TBS) pH 7.4, cage-like particles formed at compositions
      with high proportions of DC-CHOL and had a strongly positive zeta-potential.
      These could be purified by differential centrifugation. With phosphate buffered
      saline pH 7.4, the formation of cage-like particles was much reduced. It was
      shown that the formation of cage-like particles with a positive charge depended
      on suitable concentrations of TRIS in the hydration buffer.

PMID- 15986470
TI  - Kinetics of iron-mediated artemisinin degradation: effect of solvent composition
      and iron salt.
AB  - The antimalarial endoperoxides, such as artemisinin, are postulated to exert
      their potent parasiticidal activity via the formation of reactive intermediates
      in the iron-rich infected erythrocyte. The in vitro chemical reaction profile of
      putative endoperoxide antimalarials and ferrous iron is often qualitatively used
      to assess their potential antimalarial activity and to develop a structure
      reactivity relationship. This study utilized LCMS to monitor the kinetics of
      artemisinin degradation and product formation in the presence of iron. A second
      order degradation reaction (k = 18 M(-1) h(-1)) was observed from the reaction of
      artemisinin with ferrous sulphate in aqueous acetonitrile to produce a number of
      stable isomeric rearrangement products. A systematic study of the effect of a
      number of solvent systems and different iron salts showed pronounced changes in
      reaction rate and product distribution. The significant effects observed in the
      current study highlight the need to carefully control reaction conditions when
      studying peroxide antimalarial stability or attempting to develop in vitro/in
      vivo correlations of endoperoxide antimalarials and their reactivity with iron.

PMID- 15986472
TI  - Erosion of microbicide formulation coating layers: effects of contact and
      shearing with vaginal fluid or semen.
AB  - An effective vaginal microbicide formulation must distribute and maintain an
      epithelial coating layer. The post-application durability of this coating is
      significantly affected by the vaginal environment. A new in vitro assay
      quantified coating layer erosion after contact and shear with simulated vaginal
      fluid or semen. Coating layer persistence and viscosity of both fluid and gel
      layers were assessed versus time. Five vaginal formulations were studied. In all
      gels, there was an overall trend of rapid ( approximately 30 min) and significant
      viscosity loss. Although there were differences across gels and between
      simulants, greater erosion occurred after contact with the low-pH vaginal fluid
      simulant (>50% viscosity decrease), as compared to an alkaline semen simulant.
      These in vitro results suggest significant differences in vivo of vaginal coating
      retention by the test gels. This new assay can be diversified to create a
      spectrum of biologically relevant conditions which collectively simulate the
      natural history of vaginal formulation residence.

PMID- 15986473
TI  - Requirement for P granules and meiosis for accumulation of the germline RNA
      helicase CGH-1.
AB  - In Caenorhabditis elegans, lack of the conserved germline RNA helicase CGH-1
      causes infertility and excessive levels of physiological germline apoptosis, a
      process that normally claims about half of all developing oocytes. In yeast the
      CGH-1 ortholog is a key component of degradative "processing (P) bodies," which
      may share some properties with germline protein-RNA complexes such as P granules.
      During oogenesis CGH-1 associates with P granules, but also accumulates to high
      levels in additional cytoplasmic particles. Here we show that appropriate levels
      and localization of CGH-1 depends on some P granule components and on mechanisms
      that establish meiotic development. At the same time, germ cell death is not
      increased by various abnormalities in P granules or meiosis. We conclude that in
      developing oocytes CGH-1 particles accumulate specifically in response to meiotic
      development and have distinct functions from P granules, and may be dynamic
      protein-mRNA structures.

PMID- 15986474
TI  - Origin, fate, and function of the components of the avian germ disc region and
      early blastoderm: role of ooplasmic determinants.
AB  - In the avian oocytal germ disc region, at the end of oogenesis, we discerned four
      ooplasms (alpha, beta, gamma, delta) presenting an onion-peel distribution (from
      peripheral and superficial to central and deep. Their fate was followed during
      early embryonic development. The most superficial and peripheral alpha ooplasm
      plays a fundamental role during cleavage. The beta ooplasm, originally localized
      in the peripheral region of the blastodisc, becomes mainly concentrated in the
      primitive streak. At the moment of bilateral symmetrization, a spatially oblique,
      sickle-shaped uptake of gamma and delta ooplasms occurs so that gamma and delta
      ooplasms become incorporated into the deeper part of the avian blastoderm. These
      ooplasms seem to contain ooplasmic determinants that initiate either early
      neurulation or gastrulation events. The early neural plate-inducing structure
      that forms a deep part of the blastoderm is the delta ooplasm-containing
      endophyll (primary hypoblast). Together with the primordial germ cells, it is
      derived from the superficial centrocaudal part of the nucleus of Pander, which
      also contains delta ooplasm. The other structure (gamma ooplasm) that is
      incorporated into the caudolateral deep part of the blastoderm forms Rauber's
      sickle. It induces gastrulation in the concavity of Rauber's sickle and blood
      island formation exterior to Rauber's sickle. Rauber's sickle develops by
      ingrowth of blastodermal cells into the gamma ooplasm, which surrounds the
      nucleus of Pander. Rauber's sickle constitutes the primary major organizer of the
      avian blastoderm and generates only extraembryonic tissues (junctional and sickle
      endoblast). By imparting positional information, it organizes and dominates the
      whole blastoderm (controlling gastrulation, neurulation, and coelom and
      cardiovascular system formation). Fragments of the horns of Rauber's sickle
      extend far cranially into the lateral quadrants of the unincubated blastoderm, so
      that often Rauber's sickle material forms three quarters of a circle. This
      finding explains the regulative capacities of isolated blastoderm parts, with the
      exception of the anti-sickle region and central blastoderm region, where no
      Rauber's sickle material is present. In avian blastoderms, there exists a
      competitive inhibition by Rauber's sickle on the primitive streak and neural
      plate-inducing effects of sickle endoblast. Avian primordial germ cells contain
      delta ooplasm derived from the superficial part of the nucleus of Pander. Their
      original deep and central ooplasmic localization has been confirmed by the use of
      a chicken vasa homologue. We conclude that the unincubated blastoderm consists of
      three elementary tissues: upper layer mainly containing beta ooplasm, endophyll
      containing delta ooplasm, and Rauber's sickle containing gamma ooplasm). These
      elementary tissues form before the three classic germ layers have developed.

PMID- 15986475
TI  - Camptocormia in a patient with multiple system atrophy.
AB  - The term "camptocormia" describes a severe forward-flexed posture. Although
      initially used to describe a conversion disorder, early authors also recognized
      organic camptocormia occurring in old age, or "camptocormie senile," as well as
      traumatic and arthritic camptocormia. More recently, camptocormia has been
      described in patients with Parkinson's disease and in an individual with
      parkinsonism. We describe a case of progressive camptocormia as part of the
      initial presentation of a patient with multiple system atrophy.

PMID- 15986476
TI  - Influence of macromolecular crowding upon the stability and state of association
      of proteins: predictions and observations.
AB  - The concept of excluded volume and possible effects of excluded volume on the
      reactivity of macromolecules in highly volume-occupied or "crowded" media are
      introduced and briefly summarized. Theoretical and experimental studies of the
      effect of crowding on protein folding and unfolding, and on the effect of
      crowding on protein association and aggregation, are reviewed. Possible effects
      of the effect of crowding on an initially native protein that can undergo
      unfolding, self-association of native protein, and/or aggregation of non-native
      protein are considered.

PMID- 15986477
TI  - CO2 laser surgery in the treatment of glottic cancer.

PMID- 15986478
TI  - Nude thymic rudiment lacking functional foxn1 resembles respiratory epithelium.
AB  - The epithelial compartment of the thymus arises from endoderm of the 3rd
      pharyngeal pouch. As it moves from a cervical to a mediastinal position during
      development, this epithelium becomes populated by lymphoid progenitor cells from
      the blood and begins to support their differentiation along the T cell lineage.
      Productive differentiation of thymic epithelium is strictly dependent on the
      foxn1 transcription factor, as evidenced by the lack of functional thymic tissue
      in nude mice that carry a spontaneous loss-of-function mutation of foxn1.
      Evaluation of the thymic rudiment epithelium from nude mice revealed phenotypic
      properties and tissue organization that was strongly reminiscent of respiratory
      epithelium. These data suggest that foxn1 may be involved in directing lineage
      choices of multi-potential progenitor epithelial cells rather than simply
      affecting the terminal differentiation program of epithelial cells specified to a
      thymic fate.

PMID- 15986479
TI  - Analysis of the shortvein cis-regulatory region of the decapentaplegic gene of
      Drosophila melanogaster.
AB  - In mammals, the Transforming Growth Factor-beta (TGF-beta) superfamily controls a
      variety of developmental processes. In Drosophila, by contrast, a single member
      of the superfamily, decapentaplegic (dpp) performs most TGF-beta developmental
      functions. The complexity of dpp functions is reflected in the complex cis
      regulatory sequences that flank the gene. Dpp is divided into three regions: Hin,
      including the protein-coding exons; disk, including 3' cis-regulatory sequences;
      and shortvein (shv), including noncoding exons and 5' cis-regulatory sequences.
      We analyzed the cis-regulatory structure of the shortvein region using a nested
      series of rearrangement breakpoints and rescue constructs. We delimit the
      molecular regions responsible for three mutant phenotypes: larval lethality, wing
      venation defects, and head capsule defects. Multiple overlapping elements are
      responsible for larval lethality and wing venation defects. However, the area
      regulating head capsule formation is distinct, and resides 5' to these elements.
      We have demonstrated this by isolating and describing two novel dpp alleles,
      which affect only the adult head capsule.

PMID- 15986480
TI  - Developmental expression and comparative genomic analysis of Xenopus cardiac
      myosin heavy chain genes.
AB  - Myosin heavy chains (MHC) are cytoskeletal motor proteins essential to the
      process of muscle contraction. We have determined the complete sequences of the
      Xenopus cardiac MHC genes, alpha-MHC and ventricular MHC (vMHC), and have
      characterized their developmental expression profiles. Whereas alpha-MHC is
      expressed from the earliest stages of cardiac differentiation, vMHC transcripts
      are not detected until the heart has undergone chamber formation. Early
      expression of vMHC appears to mark the cardiac conduction system, but expression
      expands to include the ventricle and outflow tract myocardium during subsequent
      development. Sequence comparisons, transgenic expression analysis, and
      comparative genomic studies indicate that Xenopus alpha-MHC is the true
      orthologue of the mammalian alpha-MHC gene. On the other hand, we show that the
      Xenopus vMHC gene is most closely related to chicken ventricular MHC (vMHC1) not
      the mammalian beta-MHC. Comparative genomic analysis has allowed the detection of
      a mammalian MHC gene (MyH15) that appears to be the orthologue of vMHC, but
      evidence suggests that this gene is no longer active.

PMID- 15986481
TI  - High-dose-rate brachytherapy as part of a multidisciplinary treatment of
      nasopharyngeal lymphoepithelioma in childhood.
AB  - BACKGROUND: Nasopharyngeal carcinoma in childhood is rare. Radiochemotherapy is
      considered the standard treatment and yields increased survival and local control
      rates. In this article, the authors report on the results from the
      multidisciplinary treatment of pediatric patients who had nasopharyngeal
      lymphoepithelioma with radiochemotherapy, including high-dose-rate brachytherapy
      of the primary tumor site. METHODS: Between May 1992 and May 2000, 16 children
      with nasopharyngeal lymphoepithelioma received neoadjuvant chemotherapy,
      conventional external beam radiotherapy, high-dose-rate brachytherapy, and
      adjuvant chemotherapy. Patients ranged in age from 7 years to 18 years, and 9
      patients were male. Patient distribution according to clinical disease stage was
      as follows: Stage III, 1 patient; Stage IVA, 5 patients; Stage IVB, 9 patients;
      and Stage IVC, 1 patient. Three cycles of neoadjuvant and adjuvant chemotherapy
      in 3-week intervals were administered with cyclophosphamide, vincristine,
      doxorubicin, and cisplatin. The median doses of external beam radiotherapy to the
      primary tumor, positive lymph nodes, and subclinical areas of disease were 55
      grays (Gy), 55 Gy, and 45 Gy, respectively. Children received 2 insertions of
      high-dose-rate brachytherapy at 5 Gy per insertion: These were performed with
      metallic applicators inserted through the transnasal access under local
      anesthesia. RESULTS: The median of follow-up was 54 months. At the time of last
      follow-up, 13 patients were alive without disease, 2 patients had died of
      disease, and 1 patient had died of treatment-related cardiac failure. Local
      control was achieved in 15 of 16 patients. Chemotherapy-related and radiotherapy
      related acute toxicity was relevant but tolerable. CONCLUSIONS: In the current
      study, it was shown that the treatment was effective in the control of both local
      and distant disease, although there was relevant acute and late toxicity. High
      dose-rate brachytherapy was deliverable on an outpatient basis with local
      anesthesia. Close follow-up of these patients was necessary to evaluate the
      significance of treatment-related late effects and their impact on quality of
      life.

PMID- 15986482
TI  - Percutaneous biopsy of pediatric solid tumors.
AB  - BACKGROUND: The objective of the current study was to determine the diagnostic
      accuracy of percutaneous biopsy of pediatric solid tumors, a procedure that is
      less invasive than open biopsy. METHODS: The authors conducted a retrospective
      analysis of clinical data related to 202 percutaneous core-needle biopsies of
      solid tumors at St. Jude Children's Research Hospital over 5.5 years (from 1997
      to 2003). In 103 patients, the procedure was performed to establish an initial
      diagnosis of a suspected malignancy; and, in 99 patients, disease recurrence was
      suspected. Biopsies were guided by ultrasound, computed tomography, or
      fluoroscopic imaging. From each tumor, 1-17 core biopsy samples (median, 6
      samples) were obtained; the median needle size was 15 gauge (range, 13-20 gauge).
      The specimens were submitted for histopathologic analysis and other ancillary
      procedures (molecular pathology and/or cytogenetic analyses). The accuracy of the
      diagnoses from the biopsies was determined by subsequent surgery with or without
      pathologic assessment or by outcome. RESULTS: When the biopsy samples were
      assessed for the presence of malignancy, there were 121 true-positive results
      (90% sensitivity), 67 true-negative results (100% specificity), and 14 false
      negative results (93% accuracy). In 103 tumors, when the procedure was performed
      for initial diagnosis, percutaneous needle biopsy showed a sensitivity of 97%, a
      specificity of 100%, and an accuracy of 98%. The 99 procedures for suspected
      recurrence were less reliable (sensitivity, 83%; specificity, 100%; accuracy,
      88%). CONCLUSIONS: Image-guided percutaneous biopsy was highly accurate and safe
      in the diagnosis of pediatric malignant solid tumors. This technique may be able
      to supplant diagnostic open biopsy.

PMID- 15986483
TI  - Dll1 is a downstream target of Tbx6 in the paraxial mesoderm.
AB  - Tbx6 is a member of the T-box family of transcription factors. In the mouse, Tbx6
      is expressed in the primitive streak, tail bud, and presomitic mesoderm and is
      essential for the specification of posterior paraxial mesoderm; in its absence,
      posterior somites are replaced by ectopic neural tubes. Analysis of embryos
      expressing reduced levels of Tbx6 also revealed that it is required for the
      correct patterning of the somites as well as their initial specification. As a
      first step toward identifying downstream targets of Tbx6, we examined the DNA
      binding properties of Tbx6 and identified a Tbx6 consensus binding site.
      Previously, we have shown that expression of Dll1, which encodes a Notch ligand,
      is lost in the Tbx6 mutant and that Tbx6 and Dll1 genetically interact,
      indicating that Dll1 may be a direct target of Tbx6 in the paraxial mesoderm. We
      uncovered four putative Tbx6 binding sites within a Dll1 paraxial mesoderm
      enhancer and show that Tbx6 can bind two of these sites in vitro. Altogether,
      these results lend further support for Dll1 being a direct target of Tbx6 in the
      presomitic mesoderm.

PMID- 15986484
TI  - Generation of a Bmp2 conditional null allele.
AB  - Bone morphogenetic proteins (Bmp's) are known to play many important roles in
      embryogenesis. In addition, recent data from human genetic studies has revealed
      that Bmp's also have important functions in maintenance of the adult phenotype
      and aging. The original Bmp2 germline null allele resulted in lethality at
      embryonic day 7.0-10.5 due to malformation of the amnion/chorion and cardiac
      malformations. Because the early embryonic lethality of the Bmp2 germline null
      allele hinders further investigation into Bmp2 function at later stages, we
      generated a Bmp2 conditional null allele. Using gene targeting in mouse embryonic
      stem (ES) cells, we introduced LoxP sites upstream and downstream of Bmp2 exon 3
      that encodes the mature peptide. Our results indicate that the Bmp2 conditional
      null allele is a true conditional null that encodes wildtype activity and reverts
      to a null allele after cre recombinase-induced recombination.

PMID- 15986485
TI  - Synthetic neomycin-kanamycin phosphotransferase, type II coding sequence for gene
      targeting in mammalian cells.
AB  - The bacterial neomycin-kanamycin phosphotransferase, type II enzyme is encoded by
      the neo gene and confers resistance to aminoglycoside drugs such as neomycin and
      kanamycin-bacterial selection and G418-eukaryotic cell selection. Although widely
      used in gene targeting in mouse embryonic stem cells, the neo coding sequence
      contains numerous cryptic splice sites and has a high CpG content. At least the
      former can cause unwanted effects in cis at the targeted locus. We describe a
      synthetic sequence, sneo, which encodes the same protein as that encoded by neo.
      This synthetic sequence has no predicted splice sites in either strand, low CpG
      content, and increased mammalian codon usage. In mouse embryonic stem cells sneo
      expressability is similar to neo. The use of sneo in gene targeting experiments
      should substantially reduce the probability of unwanted effects in cis due to
      splicing, and perhaps CpG methylation, within the coding sequence of the
      selectable marker.

PMID- 15986486
TI  - Efficient recombination in pancreatic islets by a tamoxifen-inducible Cre
      recombinase.
AB  - We generated pdx1(PB)CreERtrade mark transgenic mice in which a pancreatic
      endocrine-specific enhancer (pdx1(PB)) drives expression of a tamoxifen (TM)
      inducible Cre recombinase/estrogen receptor fusion protein. We previously showed
      that this enhancer directs expression to immature endocrine cells as well as
      postnatal islets. This transgene provides spatial and temporal control of gene
      inactivation in pancreatic islets. Three transgenic lines were generated and
      crossed with R26R mice to assess recombination efficiency. TM-dependent lacZ
      expression was observed in islets from all three lines. One line was chosen for
      further study based on its strong islet-specific recombination in embryos and
      adults. In this line, a dose-dependent increase in recombination efficiency was
      observed in endocrine cells. Our data suggest that this transgenic line will be a
      valuable tool to inactivate genes in pancreatic endocrine cells during
      development or in the adult. The dose-dependent nature of recombination suggests
      a potential use for this line in the generation of genetic mosaic animals.

PMID- 15986487
TI  - Dental morphology and variation in theropod dinosaurs: implications for the
      taxonomic identification of isolated teeth.
AB  - Isolated theropod teeth are common Mesozoic fossils and would be an important
      data source for paleoecology biogeography if they could be reliably identified as
      having come from particular taxa. However, obtaining identifications is
      confounded by a paucity of easily identifiable characters. Here we discuss a
      quantitative methodology designed to provide defensible identifications of
      isolated teeth using Tyrannosaurus as a comparison taxon. We created a standard
      data set based as much as possible on teeth of known taxonomic affinity against
      which to compare isolated crowns. Tooth morphology was described using measured
      variables describing crown length, base length and width, and derived variables
      related to basal shape, squatness, mesial curve shape, apex location with respect
      to base, and denticle size. Crown curves were described by fitting the power
      function Y = a + bX(0.5) to coordinate data collected from lateral-view images of
      mesial curve profiles. The b value from these analyses provides a measure of
      curvature. Discriminant analyses compared isolated teeth of various taxonomic
      affinities against the standard. The analyses classified known Tyrannosaurus
      teeth with Tyrannosaurus and separated most teeth known not to be Tyrannosaurus
      from Tyrannosaurus. They had trouble correctly classifying teeth that were very
      similar to Tyrannosaurus and for which there were few data in the standard.
      However, the results indicate that expanding the standard should facilitate the
      identification of numerous types of isolated theropod teeth.

PMID- 15986488
TI  - 5'-poly(A) sequence as an effective leader for translation in eukaryotic cell
      free systems.
AB  - Poly(A) sequence of 25 adenylic residues placed immediately before the start
      codons of the green fluorescent protein (GFP) and firefly luciferase (Luc) mRNAs
      is shown to provide a high rate of translation of the heterologous messages in
      eukaryotic cell-free translation systems. Also the poly(A) leader is found to
      provide the abolition of the inhibition of translation at excess mRNA
      concentrations. The possibility of the practical use of the constructs with the
      poly(A) leader for preparative protein production is demonstrated in the wheat
      germ continuous-exchange cell-free (CECF) translation system.

PMID- 15986490
TI  - A kinetic model of quantitative real-time polymerase chain reaction.
AB  - Real-time polymerase chain reaction (PCR) is one of the most sensitive and
      accurate methods for quantifying transcript levels especially for those expressed
      at low abundance. The selective amplification of target DNA over multiple cycles
      allows its initial concentration to be determined. The amplification rate is a
      complex interplay of the operating conditions, initial reactant concentrations,
      and reaction rate constants. Experimentally, the compounded effect of all factors
      is quantified in terms of an effective efficiency, which is estimated by curve
      fitting to the amplification data. We present a comprehensive model of PCR to
      study the effect of various reactant concentrations on the amplification
      efficiency. The model is used to calculate the kinetic progression of the target
      DNA concentration with cycle number under conditions when different species are
      stoichiometrically or kinetically limiting. The reaction efficiency remains
      constant for the initial cycles. As the primer concentration becomes limiting,
      the efficiency is marked by a gradual decrease. This is in contrast to a steep
      decline under nucleotide limiting conditions. Under some conditions, commonly
      used experimentally, increasing primer concentration has the adverse effect of
      reducing the final amplified template concentration. This phenomenon seen at
      times experimentally is explained by the simulation results under rate limiting
      enzyme concentrations. Primer dimer formation is shown to significantly affect
      the reaction rates, effective efficiency, and the estimated initial
      concentrations. This model, by describing the interplay of the many operating
      variables, will be a useful tool in designing PCR conditions and evaluating its
      results.

PMID- 15986489
TI  - Bcl-x(L) mediates increased production of humanized monoclonal antibodies in
      Chinese hamster ovary cells.
AB  - Enhanced product yields, reduction in throughput time, improved cost
      effectiveness and product quality are examples of benefits gained by delaying
      apoptotic cell death in bioreactors. To examine the effect on recombinant protein
      production, bcl-x(L) was overexpressed in a CHO cell line secreting humanized
      monoclonal antibody directed against the alpha1beta1 integrin. When cell lines
      overexpressing bcl-x(L) were compared to the parent, cell viability was increased
      by 20% and titers by 80%. Total viable cell densities were similar and specific
      productivities were enhanced by almost two-fold on scale-up to bioreactors.
      Comparison in a chemically defined media demonstrated an even greater sustained
      viability in bcl-x(L) expressing cells by 50% and up to 90% increase in titer
      with no impact on product quality. Caspase 3 activities were monitored as a
      marker for apoptotic cell death. In the presence of Bcl-x(L), caspase activities
      were reduced to background levels. The role of Bcl-x(L) in protecting cells from
      premature death was further examined in studies performed in the presence of
      NaBu, at concentrations known to trigger cell death. Results demonstrated that
      cells expressing bcl-x(L) retained 88% cell viability with >2 fold increase in
      titer. Bcl-x(L) was similarly overexpressed in a different CHO cell line
      producing a humanized mAb against the chemokine MCP1. Once again, production
      titer was increased by 80% and viability by 75%. Together the studies have shown
      that overexpression of bcl-x(L) in production cell lines was able to
      significantly increase the titer by enhancing both the specific activity and
      total cell viability while maintaining product quality.

PMID- 15986491
TI  - Emulsion strategies in the microencapsulation of cells: pathways to thin coherent
      membranes.
AB  - Microencapsulation of cell spheroids in an immunoselective, highly biocompatible,
      biomembrane offers a way to create viable implantation options in the treatment
      of insulin-dependent diabetes mellitus (IDDM). Traditionally the encapsulation
      process has been achieved through the injection/extrusion of alginate/cell
      mixtures into a calcium chloride solution to produce calcium alginate capsules
      around the cells. A novel alternative is explored here through a procedure using
      an emulsion process to produce thin adherent calcium alginate membranes around
      cell spheroids. In this study, a thorough investigation has been used to
      establish the emulsion process parameters that are critical to the formation of a
      coherent alginate coat both on a model spheroid system and subsequently on cell
      spheroids. Optical and fluorescence microscopy are used to assess the morphology
      and coherence of the calcium alginate/poly-L-ornithine/alginate (APA) capsules
      produced.

PMID- 15986492
TI  - Cross-species transfer of viruses: implications for the use of viral vectors in
      biomedical research, gene therapy and as live-virus vaccines.
AB  - All living organisms are continuously exposed to a plethora of viruses. In
      general, viruses tend to be restricted to the natural host species which they
      infect. From time to time viruses cross the host-range barrier expanding their
      host range. However, in very rare cases cross-species transfer is followed by the
      establishment and persistence of a virus in the new host species, which may
      result in disease. Recent examples of viruses that have crossed the species
      barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever
      viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI),
      monkeypox virus, and the SARS-associated coronavirus (SARS-CoV). The
      opportunities for cross-species transfer of mammalian viruses have increased in
      recent years due to increased contact between humans and animal reservoirs.
      However, it is difficult to predict when such events will take place since the
      viral adaptation that is needed to accomplish this is multifactorial and
      stochastic. Against this background the intensified use of viruses and their
      genetically modified variants as viral gene transfer vectors for biomedical
      research, experimental gene therapy and for live-vector vaccines is a cause for
      concern. This review addresses a number of potential risk factors and their
      implications for activities with viral vectors from the perspective of cross
      species transfer of viruses in nature, with emphasis on the occurrence of host
      range mutants resulting from either cell culture or tropism engineering. The
      issues are raised with the intention to assist in risk assessments for activities
      with vector viruses.

PMID- 15986493
TI  - Protective effect of vitamin B6 in chromium-induced oxidative stress in liver.
AB  - The aim of this study was to examine the efficacy of vitamin B6 against chromium
      (Cr)-induced oxidative stress. Adult male albino Wistar rats (100-120 g) were
      used in this study. Potassium dichromate, a Cr VI compound, was administered at a
      dose of 127 mg kg(-1) p.o. Vitamin B6 (pyridoxine hydrochloride) was administered
      at a dose of 100 mg kg(-1) p.o. either alone or 12 h prior to Cr or
      simultaneously with Cr. Chromium treatment induced oxidative stress in the liver
      as measured by increased lipid peroxidation (LPO) and decreased vitamin C,
      vitamin E, glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT),
      superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione
      reductase (GR). Both pre- and simultaneous treatments countered Cr-induced
      oxidative stress; pre-treatment was more effective than concurrent
      administration. The results demonstrate the antioxidant potential of vitamin B6.

PMID- 15986494
TI  - Structure elucidation and 3D solution conformation of the antibiotic enduracidin
      determined by NMR spectroscopy and molecular dynamics.
AB  - Enduracidin and ramoplanin belong to the large family of cyclodepsipeptide
      antibiotics, highly effective against Gram-positive bacteria. The primary and 3D
      solution structure of ramoplanin is already well known, and the primary structure
      of enduracidin has been determined by a combination of chemical and NMR
      spectroscopic methods. Both antibiotics share a similar peptide core of 17 amino
      acids and differ mainly in the length of the acyl chain and the presence of two D
      mannose moieties in ramoplanin. Based on the high sequence homology with
      ramoplanin, the structure in solution of enduracidin is modeled as a cyclic
      peptide. The tertiary structure thus obtained was refined through molecular
      dynamics (MD) simulation, in which the interatomic NOE-derived distance
      restraints were imposed. MD simulations yielded a family of representative 3D
      structures (RMSD = 0.89), which highlighted a backbone geometry similar to that
      of ramoplanin in its beta-hairpin arrangement. In contrast, enduracidin displays
      a different arrangement of the side-chain and of the residues forming the
      hydrophobic core.

PMID- 15986495
TI  - 1H chemical shifts in NMR: Part 22-Prediction of the 1H chemical shifts of
      alcohols, diols and inositols in solution, a conformational and solvation
      investigation.
AB  - The (1)H NMR spectra of a number of alcohols, diols and inositols are reported
      and assigned in CDCl(3), D(2)O and DMSO-d(6) (henceforth DMSO) solutions. These
      data were used to investigate the effects of the OH group on the (1)H chemical
      shifts in these molecules and also the effect of changing the solvent. Inspection
      of the (1)H chemical shifts of those alcohols which were soluble in both CDCl(3)
      and D(2)O shows that there is no difference in the chemical shifts in the two
      solvents, provided that the molecules exist in the same conformation in the two
      solvents. In contrast, DMSO gives rise to significant and specific solvation
      shifts. The (1)H chemical shifts of these compounds in the three solvents were
      analysed using the CHARGE model. This model incorporates the electric field,
      magnetic anisotropy and steric effects of the functional group for long-range
      protons together with functions for the calculation of the two- and three-bond
      effects. The long-range effect of the OH group was quantitatively explained
      without the inclusion of either the C--O bond anisotropy or the C--OH electric
      field. Differential beta and gamma effects for the 1,2-diol group needed to be
      included to obtain accurate chemical shift predictions. For DMSO solution the
      differential solvent shifts were calculated in CHARGE on the basis of a similar
      model, incorporating two-bond, three-bond and long-range effects. The analyses of
      the (1)H spectra of the inositols and their derivatives in D(2)O and DMSO
      solution also gave the ring (1)H,(1)H coupling constants and for DMSO solution
      the CH--OH couplings and OH chemical shifts. The (1)H,(1)H coupling constants
      were calculated in the CHARGE program by an extension of the cos(2)phi equation
      to include the orientation effects of electronegative atoms and the CH--OH
      couplings by a simple cos(2)phi equation. Comparison of the observed and
      calculated couplings confirmed the proposed conformations of myo-inositol, chiro
      inositol, quebrachitol and allo-inositol. The OH chemical shifts were also
      calculated in the CHARGE program. Comparison of the observed and calculated OH
      chemical shifts and CH.OH couplings suggested the existence of intramolecular
      hydrogen bonding in a myo-inositol derivative.

PMID- 15986496
TI  - Metabolic profile of lettuce leaves by high-field NMR spectra.
AB  - A detailed analysis of the proton high-field NMR spectra of aqueous and organic
      extracts of lettuce leaves is reported for the first time. A combination of COSY,
      TOCSY, (1)H-(13)C HSQC, (1)H-(13)C HMBC bidimensional sequences and DOSY was used
      to assign each spin system and to separate the components of the complex
      patterns. A large number of water-soluble metabolites belonging to different
      classes such as carbohydrates, polyols, organic acids and amino acids were fully
      assigned. Moreover, the complex spectra of metabolites extracted in organic
      solvents belonging to sterols, fatty acids, diacylglycerophospholipids,
      galactosyldiacylglycerols, sulpholipids, pheophytins, carotenoids and
      hydrocarbons were also assigned.

PMID- 15986497
TI  - 1H and 13C spectral assignments of an oxytocin-DTPA derivative, a ligand for
      potential receptor-specific MRI contrast agents.
AB  - A new potential ligand for paramagnetic complexes acting as a receptor-specific
      MRI contrast agent was investigated by means of one- and two-dimensional NMR
      spectroscopy and mass spectrometry. A complete assignment of the structure is
      reported.

PMID- 15986498
TI  - (1)H and (13)C NMR studies of asymmetrically substituted bis- and tris-Troger's
      bases.
AB  - The (1)H and (13)C NMR spectra of two stereoisomeric bis-Troger's bases and four
      stereoisomeric tris-Troger's bases asymmetrically substituted on the external
      aromatic rings were recorded and the corresponding signals assigned. The relative
      configuration of the stereogenic units has been unequivocally determined on the
      basis of homoallylic couplings and NOE experiments.

PMID- 15986499
TI  - Structure determination of salvadorin, a novel dimeric dihydroisocoumarin from
      Salvadora oleoides, by NMR spectroscopy.
AB  - Salvadorin, a new dimeric dihydroisocoumarin (1), was isolated from the
      chloroform fraction of Salvadora oleoides. Its chemical structure was established
      as 8-benzyl-6-[6-(6-ethyl-7-methyl-5,8-dihydro-2-naphthalenyl)-1-oxo-3,4-dihydro
      1H-isochromen-8yl]-3, 4-dihyro-1H-isochromen-1-one, through spectroscopic
      techniques and chemical analysis.

PMID- 15986500
TI  - 1H and 13C NMR spectra of N-substituted morpholines.
AB  - (1)H and (13)C NMR data for N-substituted morpholines 1-20 were measured using 1D
      (DEPT, 1D NOE difference) and 2D NMR spectroscopic methods including (1)H-(1)H
      COSY, long-range (1)H-(1)H COSY, NOESY, gHMBC and gHMQC experiments. At room
      temperature the (1)H NMR spectra of protonated compounds 2 and 9 show the chair
      conformation for the morpholine ring. Spin-spin coupling constants were deduced
      from the resolution-enhanced proton spectra.

PMID- 15986501
TI  - Binding of copper (II) ion to an Alzheimer's tau peptide as revealed by MALDI-TOF
      MS, CD, and NMR.
AB  - The tau protein plays an important role in some neurodegenerative diseases
      including Alzheimer's disease (AD). Neurofibrillary tangles (NFTs), a biological
      marker for AD, are aggregates of bundles of paired helical filaments (PHFs). In
      general, the alpha-sheet structure favors aberrant protein aggregates. However,
      some reports have shown that the alpha-helix structure is capable of triggering
      the formation of aberrant tau protein aggregates and PHFs have a high alpha-helix
      content. In addition, the third repeat fragment in the four-repeat microtubule
      binding domain of the tau protein (residues 306-336:
      VQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQ, according to the longest tau protein) adopts a
      helical structure in trifluoroethanol (TFE) and may be a self-assembly model in
      the tau protein. In the human brain, there is a very small quantity of copper,
      which performs an important function. In our study, by means of matrix assisted
      laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS),
      circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy, the
      binding properties of copper (II) ion to the R3 peptide derived from the third
      repeat fragment (residues 318-335: VTSKCGSLGNIHHKPGGG) have been investigated.
      The results show that copper ions bind to the R3 peptide. CD spectra, ultraviolet
      (UV)-visible absorption spectra, and MALDI-TOF MS show pH dependence and
      stoichiometry of Cu2+ binding. Furthermore, CD spectra and NMR spectroscopy
      elucidate the copper binding sites located in the R3 peptide. Finally, CD spectra
      reveal that the R3 peptide adopts a mixture structure of random structures, alpha
      helices, and beta-turns in aqueous solutions at physiological pH. At pH 7.5, the
      addition of 0.25 mol eq of Cu2+ induces the conformational change from the
      mixture mentioned above to a monomeric helical structure, and a beta-sheet
      structure forms in the presence of 1 mol eq of Cu2+. As alpha-helix and beta
      sheet structures are responsible for the formation of PHFs, it is hypothesized
      that Cu2+ is an inducer of self-assembly of the R3 peptide and makes the R3
      peptide form a structure like PHF. Hence, it is postulated that Cu2+ plays an
      important role in the aggregation of the R3 peptide and tau protein and that
      copper (II) binding may be another possible involvement in AD.

PMID- 15986502
TI  - Hydration of lysozyme as observed by infrared spectrometry.
AB  - Infrared spectra of a film of lysozyme 3 mum thick, immersed in an atmosphere
      displaying a relative humidity, or hygrometry, which spans the whole range from 0
      to 1 at room temperature, are recorded. The evolution of the spectra with this
      relative humidity is quantitatively analyzed on the basis of a newly proposed
      method. It allows the precise measurement of the quantity of water that remains
      embedded inside the dried sample at each stage of hydration, and the definition,
      in terms of chemical reactions of the three hydration mechanisms that correspond
      to the three hydration spectra on which all experimental spectra can be
      decomposed. With respect to preceding similar studies, some refinements are
      introduced that allow improvement of the interpretation, but that also raise some
      new questions, which mainly concern the structure of the hydrogen-bond network
      around the carbonyl peptide groups.

PMID- 15986503
TI  - Cationic cobalt(I) catalysts for the asymmetric cyclocarbonylation of 1,6-enynes.
AB  - Cobalt(I) complexes, modified with (R)-(6,6'-dimethoxybiphenyl-2,2'
      diyl)bis(diphenylphosphine) [Co((R)-MeO-Biphep)(CO)3]X (X = BF4 [1] or OTf [2]),
      were synthesized and characterized. The compounds have a trigonal bipyramidal
      structure and are fluxional. They were tested as catalyst precursors for the
      enantioselective cyclocarbonylation of 4,4-bis(carboethoxy)hept-5-en-1-yne 3.
      Enantioselectivities up to 78.5% were attained. However, activity and
      stereoselectivity are lower compared to catalytic systems based on Co2(CO)8
      modified with the same atropisomeric ligand.

PMID- 15986504
TI  - Asymmetric catalysis by chiral lanthanide complexes in water.
AB  - The development of catalytic, asymmetric transformations in water is a
      challenging task. The lanthanides are becoming reagents of choice for many Lewis
      acid-catalyzed reactions in aqueous media as they are water tolerant. However,
      enantioselective reactions catalyzed by lanthanides are difficult to achieve in
      water due to the instability of the reported catalysts. Herein we report the
      development of stable, well-defined chiral lanthanide complexes and their
      effectiveness in the asymmetric reduction of alpha-keto acids in aqueous
      solution. This is the first example of asymmetric reduction by a chiral
      lanthanide complex in water. Although modest ees are obtained (40-50%) the
      ytterbium complexes offer a unique advantage as they have the ability to monitor,
      direct from the reaction mixture, the % ee for the reaction, by 1H NMR, through a
      dipolar analysis of the observed paramagnetic shift.

PMID- 15986505
TI  - Night shifts and colorectal cancer risk.

PMID- 15986506
TI  - Pain medications. Options may be changing.

PMID- 15986507
TI  - My pharmacist told me that one of the medications I take just became available as
      a generic. Why didn't the cost go down much?

PMID- 15986508
TI  - Sexual misconduct (05/125C).

PMID- 15986509
TI  - A wildlife biologist with skin lesions.

PMID- 15986510
TI  - Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional
      study.
AB  - BACKGROUND: Carnitine facilitates the transport of long-chain fatty acids across
      the mitochondria for beta oxidation, and the removal of potentially toxic
      acylcoenzyme-A metabolites from the inner aspect of mitochondrion as
      acylcarnitines. Previous studies suggest a significant decrease in carnitine
      concentrations and changes in the ratio of acylcarnitine to free carnitine in
      seizure-disoriented patients treated with valproic acid (VPA), which may lead to
      clinical manifestations of carnitine deficiency. This study sought to explore
      whether the same decrease in plasma free carnitine and increase in acylcarnitines
      are seen when VPA is used in the treatment of patients with psychiatric disease.
      METHOD: Thirty psychiatric patients treated with VPA for at least six months were
      selected for the study and granted informed consent for participation. Exclusion
      criteria included liver disorder or pancreatitis, metabolic defects known to
      affect plasma carnitine levels, or noncompliance with VPA regimen. Plasma free
      carnitine, total carnitine, VPA, and amylase levels were determined, and liver
      function tests (LFTs) were performed. Pearson correlations were conducted between
      VPA levels, levels and ratios of carnitines, as well as LFTs and amylase levels.
      RESULTS: Plasma free and total carnitine levels were lower than the reported
      normal range for the laboratory performing the assay, and the ratio of
      acylcarnitine to free carnitine was increased. There was a significant positive
      correlation of VPA levels and acylcarnitine-free carnitine ratio, a trend toward
      significance between VPA levels and acylcarnitine levels, and a marginal negative
      correlation between VPA levels and free carnitine levels. VPA levels correlated
      also with several LFTs and acylcarnitine levels. Octanoyl carnitine and
      acylcarnitine levels, as well as acylcarnitine-free carnitine and octanoyl-free
      carnitine ratios, correlated significantly with amylase levels. CONCLUSION:
      Although the study was limited by a cross-sectional design without direct control
      comparison, the findings suggest that patients with various psychiatric
      conditions treated with polypharmacy that includes VPA may have lower plasma
      carnitine levels than would be expected in healthy controls.

PMID- 15986511
TI  - [Integration of research into the dietetic practice of New Brunswick].
AB  - In New Brunswick, we have very little information that describes practice-based
      research in dietetics. To encourage and promote research in this province, it is
      crucial to describe the place that research has in dietetic practice and
      determine the number of dietician in New Brunswick that received an education in
      research methodology. A validated questionnaire was distributed to all the
      members of the New Brunswick Association of Dietitians; 76% of the members filled
      out the questionnaire. For 85% of them, their highest level of education is the
      internship; 15% have a postgraduate degree, and 55% have completed a research
      methodology course. The dietitians having completed graduate studies perceived
      fewer barriers to the integration of practice-based research. The Barrier that
      81% of the dietitians in the province agreed was most influential in discouraging
      the implementation of research to daily practice was the time allowed for
      research at work. Nearly two-thirds (63%) agreed that it is very improbable that
      they will pursue graduate studies. The probability of pursuing graduate studies
      decreased with the age of the dietitians: 85% agreed that "family and personal
      obligations" and "lack of time" were the most important barriers in pursuing
      graduate studies. The attitude of New Brunswick dietitians towards research was
      nonetheless positive.

PMID- 15986512
TI  - Hearing the voice of medical students worldwide.

PMID- 15986513
TI  - The role of the registered dietician in dysphagia assessment and treatment: a
      discussion paper.

PMID- 15986514
TI  - Galantamine: excess mortality.

PMID- 15986515
TI  - Fatal stroke with aripiprazole.

PMID- 15986516
TI  - Tramadol addiction.

PMID- 15986517
TI  - [A role of central control in development and progression of diabetic
      polyneuropathy in teenagers].
AB  - A role of central control of peripheral nervous system was investigated in 79
      teenagers with noninsulin-dependent diabetes mellitus. The patients were studied
      using clinical and neurophysiological methods, electroneuromyography and
      somatosensory evoked potentials (SSEP). The SSEP analysis revealed the
      disturbances of sensory pathways in the central nervous system at early stage of
      diabetes mellitus. A new pathogenic mechanism of progressive polyneuropathy with
      trophic complications is presented. At the initial stage of the disease, low
      conductivity is combined with a compensating acceleration of conductivity in the
      central structures. In diabetes course, central conductivity declines and control
      over peripheral system decreases resulting in the disease progression. In trophic
      complications, acceleration of conductivity is absent already at the early
      stages, suggesting a primary weak control over the peripheral nervous system.

PMID- 15986518
TI  - [The results of brain MRI in patients with vascular and posttraumatic
      encephalopathy: a comparative study].
AB  - Using clinical, psychological methods and MRI, 199 patients with vascular (VE)
      and posttraumatic encephalopathy (PE) have been studied. It is shown that
      atherosclerosis, essential hypertension and their combination become relevant at
      the age of 40 years. Multiple microfocal white matter lesions, leukoaraiosis,
      extensive bilateral atrophic changes and dilatation of subarachnoid spaces were
      characteristic of patients with VE (mean age 67+/-10 years). In patients with PE,
      mean age 22+/-7 years, the local dilatation of subarachnoid space, unilateral
      dilatation of lateral ventricle and cystic changes in subarachnoid spaces were
      detected.

PMID- 15986520
TI  - [Psychopathological variants of irritable bowel syndrome].

PMID- 15986519
TI  - [Rare and atypical forms of spinal muscle atrophies in Saratov region].

PMID- 15986521
TI  - Achieving true, women-centred care.

PMID- 15986522
TI  - [Prevention of sudden infant death--the special responsibility of pediatric
      nurses].

PMID- 15986523
TI  - Are polyamines involved in the contractile effects of angiotensin II in the rat
      aorta? (Polyamines and angiotensin II in rat aorta).
AB  - Angiotensin II (AII) is a central factor involved in the pathophysiology of
      arterial hypertension and atherosclerosis. On the other hand, polyamines
      represent a family of organic cations with low molecular weight, playing
      intracellular regulatory roles essential for the cellular growth and
      differentiation. The cellular contents, the synthesis and the transport of
      polyamines are increased following the actions of AII, as well as of other
      cellular growth factors. Our results show that the administration of polyamines
      as pre-treatment modulates the contractile effects of extracellular AII (80 nM).
      This modulation is concentration-dependent and dual: the lower concentrations
      amplify and the higher concentrations reduce the effects of AII in the isolated
      rat aorta rings without endothelium. Moreover, DL-alpha-Difluoromethylomithine
      (DFMO), a specific inhibitor of ornithine decarboxylase, does not significantly
      modify the contractile effects of AII. Thus, these data suggest that polyamines
      generated through this metabolic pathway are not involved in the contractile
      effects of AII in rat aortic vascular smooth muscle.

PMID- 15986524
TI  - Impact of multileaf collimator leaf positioning accuracy on intensity modulation
      radiation therapy quality assurance ion chamber measurements.
AB  - Quality assurance (QA) procedures for intensity modulation radiation therapy
      (IMRT) usually involve an ion chamber measurement in a phantom using the beam
      configuration of the actual treatment plan. In our QA procedures it was observed
      that the degree of agreement between the measurement and the calculation could
      vary from plan to plan, from linac to linac, as well as over time, with a
      discrepancy up to 8%. In this paper we examine one aspect of the process which
      can contribute to such poor reproducibility, namely, the leaf end position
      accuracy. A series of measurements was designed to irradiate an ion chamber using
      small beam segments where one multileaf collimator (MLC) edge covers half of the
      chamber. It was shown that the reproducibility varied up to 13%, which provides a
      possible explanation for the observed discrepancies above. A useful tool was also
      developed to measure ionization signals from individual segments of an IMRT
      sequence. In addition, an understanding of the leaf end position variations
      offers some insight into the overall quality of an IMRT dose distribution.

PMID- 15986525
TI  - Science, fraud and the Baltimore case.

PMID- 15986526
TI  - Dying made easy.

PMID- 15986527
TI  - Rights for rodents.

PMID- 15986528
TI  - Introduction: the brain's special status.

PMID- 15986529
TI  - Straining their brains: why the case against enhancement is not persuasive.

PMID- 15986530
TI  - No veterinarian to "The naked ape" I.

PMID- 15986531
TI  - Important treatment, wrong diagnosis: enhancement is not to blame for the abuse
      of autonomy.

PMID- 15986532
TI  - Where's the wisdom?

PMID- 15986533
TI  - Neuroethics: a guide for the perplexed.
AB  - Like filings to a magnet, issues of all shapes, sizes, and degrees of importance
      are sticking to the idea of neuroethics. Martha Farah, an early thinker in this
      new field, proposes that, numerous as they are, the problems actually fall into
      just three categories. She finds that neuroethics has made a quick start sizing
      up many practical--and some unique--questions swirling up from brain science,
      but, she writes, watch for challenges that reach beyond these to the
      metaphysical. Neuroscience may one day explain in terms of neural tissue
      virtually all aspects of human cognition and emotion--realms traditionally deemed
      apart from physical law. Thus, we should also expect neuroethics to grapple with
      our fundamental distinction between persons and mere "things." If mental
      processes prove to result from purely physical events, this opens to question our
      notions of consciousness, spirituality, free will, and moral responsibility.

PMID- 15986534
TI  - Memory: Pandora's hippocampus?
AB  - Greater knowledge of the human brain has enabled us to begin devising therapies
      to rescue or modify memory for the afflicted, such as Alzheimer's patients or
      post-traumatic stress disorder victims. This same knowledge could also allow us
      to alter how normal, healthy memory operates; we may become able to enhance
      memory and learning through biological intervention. But the brain consists of
      complex, interactive networks, and unintended consequences could easily occur.
      Moreover, memory is woven into our individuality. Altering our memory processes
      therefore risks altering us fundamentally. We may not be able to resist opening
      this neuroscientific Pandora's Box, John Gabrieli writes, but we must proceed
      with all the wisdom we can muster.

PMID- 15986535
TI  - Seeking more goodly creatures.
AB  - In principle, genetic and reproductive technologies might allow "enhanced"
      children--with mental aptitudes and personal qualities improved beyond their
      expected abilities or even beyond humanity's normal range. Worry about a "brave
      new world" has already begun, but is that world imminent? And assuming that
      parents could choose traits for their children, would this be a bad thing? Many
      people think so for many different reasons, Henry Greely writes, but before we
      decide to regulate genetic enhancement, we need to decide how it differs from
      other forms of enhancement, traditional and new, and if those differences are
      important enough to justify regulation.

PMID- 15986536
TI  - Everyday neuromorality.
AB  - Increasingly, scientists are observing and recording human emotions through
      neuroimaging. Such capability is causing widespread uneasiness, writes Adina
      Roskies, for it has the potential to result in a sort of demystification of the
      mental that makes freedom of the will seem impossible and threatens to leave us
      open to manipulation as never before. Relax, the author argues: Moral
      responsibility is fundamentally social, and self-control is what makes us free.
      Understanding cognitive function may cause us to revise, but will not force us to
      abandon, common notions of moral responsibility and control.

PMID- 15986537
TI  - Ethical issues in taking neuroscience research from bench to bedside.
AB  - Dramatic advances in neuroscience have created fast-rising expectations for
      improvements in the health and well-being of people around the world. But
      fulfilling this promise is proving to be neither quick nor easy, and not for
      scientific reasons alone. Alan Leshner urges that neuroscientists not only
      address the significant challenges of their own investigations but also be
      willing to participate in ethical and legal dialogues with colleagues and non
      colleagues alike.

PMID- 15986538
TI  - A fish story? Brain maps, lie detection, and personhood.
AB  - Generations of brain-imaging studies have provided increasingly detailed
      information about the complexity of human behavior, but few lines of
      investigations better illustrate the intricacy of the brain's workings than the
      neural processes involved in lying or deceiving. And perhaps none make clearer
      the difficulty of accurately distinguishing between truthfulness and
      untruthfulness with new imaging technology. Moreover, we must ask ourselves if we
      are laying a foundation of risk regarding the very idea of creating brain maps of
      behavior and personal identity and whether these maps are ready for such real
      world applications as law, employment, and insurance. When technology of this
      kind moves out of the hands of researchers and becomes available for practical
      uses, the lives of individuals and future of our society may be profoundly
      affected.

PMID- 15986539
TI  - New neuroscience, old problems: legal implications of brain science.
AB  - Despite a large and growing interest in applying brain science to the ends of
      justice, the implications of neuroscience for the law are still unclear. But
      Stephen Morse argues that, unless discoveries about the brain radically change
      our conception of ourselves, they are unlikely to fundamentally alter legal
      doctrine. For most challenges the findings might raise to justice, equality, and
      liberty, he writes, the law has rich theoretical resources with which to address
      them. On the other hand, the author acknowledges, one can easily imagine
      substantial changes in particular doctrines.

PMID- 15986540
TI  - Blood supply and demand.

PMID- 15986541
TI  - Canada's challenge for health.

PMID- 15986542
TI  - Georgia: an unlikely stronghold for bacteriophage therapy.

PMID- 15986543
TI  - DARPA on your mind.
AB  - Applied science may once again play a decisive role in changing the face of armed
      conflict, and the rest of human affairs, by shifting the battlefield to our very
      brains. The national-security establishment--and particularly the Pentagon's
      Defense Advanced Research Projects Agency (DARPA)--supports research at the
      intersection of neuroscience and national security that could ultimately enable
      authorities to do things like enhance (or muddle, or erase) memory, monitor
      crowds for individuals whose brain patterns correlate with aggressive behaviors,
      or control weapons from afar merely with thoughts. What are the dangers of such
      information falling into "the wrong hands," and are there any "right hands" for
      this kind of knowledge? Is any extension of human abilities justified by the need
      for government to protect its society?

PMID- 15986544
TI  - Models for the neuroethical debate in the community.
AB  - Citing a line from ancient Sanskrit wisdom, "there is nothing in the world so
      purifying as knowledge," John Timpane urges the adoption of a roots-up process by
      which citizens, in organized forums, deliberate critical neuroethical issues. The
      author suggests several ways such a deliberative process might play out with some
      top neuroethics issues--enhancement, stem-cell research, and the use of
      "brainprints"--to show how the citizen groups might form consensus
      recommendations. "We have time before the wave of the new neuroscience crests,"
      he writes. "Best to discuss it now before the wave is upon us."

PMID- 15986545
TI  - Protecting the vulnerable in brain research.
AB  - Robert M. Cook-Deegan, M.D., of the Kennedy Institute of Ethics, Georgetown
      University, looks at several new attempts to forge workable policy on
      participation in clinical brain research and warns that another unresolved clash
      of interests will produce only victims. Although the issues are complex, says
      Cook-Deegan, there is ample common ground. He recommends some principles that
      could help to end the costly stalemate.

PMID- 15986546
TI  - Patents on parts of the human body: salient issues under EC and WTO law.

PMID- 15986547
TI  - Some reflections on an international convention on the banning of human cloning
      and related patents.

PMID- 15986548
TI  - Patents and human genome research in developing countries: problems and
      proposals.

PMID- 15986549
TI  - Epidemiology of asthma.

PMID- 15986550
TI  - Latex allergen sensitization due to glove use among hospital staff in Jakarta and
      related factors.
AB  - AIM: To know whether latex sensitization risk among nurses is higher than among
      administration staff and whether latex sensitization risk among operating room
      nurses is higher than among ward room nurses and also whether there is a
      correlation between sensitization and sex, age, duration-frequency of exposure,
      smoking, or atopic status. METHODS: A cross-sectional study has been conducted in
      830 persons from 6 hospitals in Jakarta consisting of 271 operating room nurses,
      287 ward room nurses, and 272 administration staff. Subjects completed a guided
      questionnaire to determine the subject's age, sex, work setting, duration and
      frequency of exposure or smoking habits and then the subjects underwent an
      allergy skin prick test with allergens Der p, Der f, Fel d and latex to determine
      atopic status and latex sensitization. RESULTS: The proportion of latex
      sensitization among nurses was 6.1% and among administration staff 1.5%; there
      was a significant difference (p=0.002). The proportion between operating room
      nurses was 6.3% and among ward room nurses 5.9%; there was no significant
      difference (p=0.974). There was a significant correlation between sensitization
      and mild or severe exposure or atopic status, but no significant correlation
      between sensitization and sex, age, duration of exposure, or smoking. CONCLUSION:
      The risk of latex sensitization among nurses is higher than among administration
      staff, but the risk among operating room nurses was similar to ward room nurses.
      Atopic status and frequency of exposure were both associated with latex
      sensitization.

PMID- 15986551
TI  - Prevalence of hypertension without anti-hypertensive medications and its
      association with social demographic characteristics among 40 years and above
      adult population in Indonesia.
AB  - AIM: To find out the prevalence of hypertension without anti-hypertensive
      medication and its social demographic risk factors among adult population in
      Indonesia. METHODS: Random samples of 3080 subjects aged 40-94 years were
      obtained from various districts in every big island in Indonesia. Blood pressure
      measurements, as well as assessment on history of hypertension, use of anti
      hypertensive medications, and social demographic characteristics were performed.
      Blood pressure measurements were obtained by trained doctors with the subjects in
      supine position. Stepwise multiple logistic regression was used to determine
      variables which were most associated with treatment without anti-hypertensive
      medication in hypertensive subjects. RESULTS: The prevalence of hypertension
      without anti-hypertensive medication among 40 years and above adult population in
      Indonesia was 37.32% (677 our of 1814 hypertensive subjects). From bivariate
      analysis, we found that male sex, older age, informal education and unemployment
      were associated with the use of anti-hypertensive medication. Multivariate
      analysis shows that male sex (OR=1.33), education level of elementary school
      (OR=1.50), and government employment (OR=1.24) are significantly as risk factors
      for not taking anti-hypertensive medication. Age more than 60 years old (OR=0.49)
      and unemployment (OR=0.70) are protective factors for not taking anti
      hypertensive medication. CONCLUSION: The prevalence of hypertension without anti
      hypertensive medication in this study is higher than the prevalence found in some
      other studies, and due to several social demographic risk factors, such as low
      level education, male sex, and being government employees. On the other hand,
      older people and those who have no formal occupation are protective factors.

PMID- 15986552
TI  - Dutch government urged to inform public of blood mistakes.

PMID- 15986553
TI  - MEP warns of growing threat of patient mobility.

PMID- 15986554
TI  - Cardiac arrest during pregnancy.
AB  - This case involves cardiac arrest of a 29-week old pregnant African American
      woman, occurring 2 days after surgical correction of an incarcerated ventral
      hernia with small bowel obstruction. The patient could not be resuscitated from
      this arrest. Details of the case are presented, and diagnostic and unique
      management considerations for this uncommon occurrence are set forth.

PMID- 15986555
TI  - [Planning of periodontal therapy and quality control in periodontal management].

PMID- 15986556
TI  - AR:12-hour-shift RN falls on trip to cafeteria: workers' compensation benefits
      awarded to nurse.

PMID- 15986557
TI  - Defining the personal health record. AHIMA releases definition, attributes of
      consumer health record.

PMID- 15986558
TI  - Designing effective training.

PMID- 15986559
TI  - Turning grads into employees. Intern program delivers what grads and employers
      both want: experience.

PMID- 15986560
TI  - Going the distance. Balancing work and education in a distance learning program.

PMID- 15986561
TI  - RHIA reality check. RHIAs rate 195 tasks and 90 knowledge areas in job analysis
      survey.

PMID- 15986562
TI  - Informatics: How an emerging field of study benefits HIM.

PMID- 15986563
TI  - The certificate of destruction: what it is, what it's not.

PMID- 15986564
TI  - Medicare billing in long-term care.

PMID- 15986565
TI  - An update on the NHIN and RHIOs.

PMID- 15986566
TI  - EHR career opportunities: sample HIM job descriptions.

PMID- 15986567
TI  - How to safely recycle PCs.

PMID- 15986568
TI  - The necessary coding skills: what employers are looking for in coding
      professionals.

PMID- 15986569
TI  - Beyond coding to content analysis.

PMID- 15986570
TI  - Coder uses education as a pathway to success.

PMID- 15986571
TI  - Percutaneous absorption of arsenic from environmental media.
AB  - Current knowledge of percutaneous absorption of arsenic is based on studies of
      rhesus monkeys using soluble arsenic in aqueous solution, and soluble arsenic
      mixed with soil (Wester et al., 1993). These studies produced mean dermal
      absorption rates in the range of 2.0-6.4% of the applied dose. Subsequently,
      questions arose as to whether these results represent arsenic absorption from
      environmental media. Factors such as chemical interactions, the presence of other
      metals, and the effects of weathering on environmental media all can affect the
      nature of arsenic and its potential for percutaneous absorption. Therefore,
      research specific to more relevant matrices is important. The focus of this
      effort is to outline study design considerations, including particle size,
      application rates, means of ensuring skin contact and appropriate statistical
      evaluation of the data. Appropriate reference groups are also important. The
      potential for background exposure to arsenic in the diet possibly obscuring a
      signal from a dermally applied dose of arsenic will also be addressed. We
      conclude that there are likely to be many site- or sample-specific factors that
      will control the absorption of arsenic, and matrix-specific analyses may be
      required to understand the degree of percutaneous absorption.

PMID- 15986572
TI  - Ratios of N-(2,3,4-trihydroxybutyl) valine and N-(2-hydroxy-3-butenyl) valine
      formed hemoglobin adducts in female mice inhalation exposure with 1,3-butadiene.
AB  - 1,3-Butadiene (BD) is a known rodent and probable human carcinogen (IARC, group
      2A) or 'known to be a human carcinogen' (Department of Health and Human Services,
      2000). Exposure to BD can occur either via petrochemical products or through the
      general environment. Adducts can be used as biomarkers for biological monitoring
      of carcinogen exposure. This study investigated the hemoglobin adducts in blood
      after inhalation exposure to BD in ICR female mice for three weeks (5 h/day x 5
      days/week). During the inhalation exposure, the body weights of mice were
      significantly lower from day 9 onward for the 500 ppm BD group and from day 4
      onward for the 1000 ppm BD group. On the 1st, 2nd and 3rd weeks after inhalation
      exposure, the concentrations of HB Val adducts were 1.8, 3.7 and 6.2 pmol/mg
      globin for the 500 ppm BD group, and 5.7, 7.4 and 16.0 pmol/mg globin for the
      1000 ppm BD group. The concentrations of THB Val adducts were 32.0, 42.0 and 55.0
      pmol/mg globin for the 500 ppm BD group, and 67.8, 72.7 and 83.5 pmol/mg globin
      for the 1000 ppm BD group. Their defined ratios were higher at the earlier
      exposure period and at the lower concentration. They were 17.8, 11.4 and 8.87 for
      the 500 ppm BD group, and 11.9, 9.8 and 5.2 for the 1000 ppm BD group, on the
      1st, 2nd and 3rd weeks after inhalation exposure. THB Val and HB Val adducts
      appear to be the important hemoglobin adducts for monitoring BD exposure, with
      the latter being a more predictable biomarker than the former.

PMID- 15986573
TI  - Active smoking causes oxidative stress and decreases blood melatonin levels.
AB  - Oxidative effects via free radical generation in smokers have been widely
      investigated. They cause lipid peroxidation, oxidation of proteins and damage to
      mainly lung and other tissues. In humans, antioxidative capacity of serum is
      related to antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px) and melatonin. The effect of cigarette smoking on plasma levels of
      melatonin and antioxidant enzymes has not been established together yet. Also, it
      may not be clear if melatonin levels are affected by smoking and melatonin has a
      protective effect on cigarette smoking-induced free radical damage. The aim of
      this study is to investigate the relationship between smoking and antioxidant
      capacity including melatonin, a powerful endogenous antioxidant, and antioxidant
      enzymes in teenage girls who are active smokers. Additionally, malondialdehyde
      (MDA) levels were determined in those who have smoked at least one packet a day
      for three or more years. MDA levels have been used as a convenient index of the
      lipid peroxidation-related oxidative damage of tissues. Twenty-one young female
      active smokers who study at the School of Nursing and 21 nonsmoking students (as
      controls) at the same school were included in the study. The activities of two
      principal antioxidant enzymes SOD, GSH-Px and plasma levels of MDA were
      significantly increased but melatonin content of the blood was significantly
      decreased as compared to nonsmokers. In spite of an increase in antioxidant
      enzyme activities, MDA levels were slightly increased in smokers. This indicates
      that antioxidant self-defence mechanisms may not sufficiently protect the
      respiratory system from smoke-mediated oxidative injury. This result may be
      related to low melatonin levels in teenage female smokers. It seems that
      melatonin can reduce free radical damage to the respiratory system induced by
      cigarette smoke. Further experimental investigations with exogenous melatonin
      treatments will be needed.

PMID- 15986574
TI  - No effects of 900 MHz and 1800 MHz electromagnetic field emitted from cellular
      phone on nocturnal serum melatonin levels in rats.
AB  - In this study, the effects of exposure to a 900 MHz and 1800 MHz electromagnetic
      field (EMF) on serum nocturnal melatonin levels of adult male Sprague-Dawley rats
      were studied. Thirty rats were used in three independent groups, 10 of which were
      exposed to 900 MHz, 10 of which were exposed to 1800 MHz and 10 of which were
      sham-exposed (control). The exposures were performed 30 min/day, for five
      days/week for four weeks to 900 MHz or 1800 MHz EMF Control animals were kept
      under the same environmental conditions as the study groups except with no EMF
      exposure. The concentration of nocturnal melatonin in the rat serum was measured
      by using a radioimmunoassay method. There were no statistically significant
      differences in serum melatonin concentrations between the 900 MHz EMF group and
      the sham-exposed group (P > 0.05). The values at 12:00 pm were 39.11 +/- 6.5
      pg/mL in the sham-exposed group and 34.97 +/- 5.1 pg/mL in the 900 MHz EMF
      exposed group. Also, there were no statistically significant differences in serum
      melatonin concentrations between the sham-exposed group and the 1800 MHz EMF
      exposed group (P > 0.05). The values at 12:00 pm were 39.11 +/- 6.5 pg/mL in the
      sham-exposed group and 37.96 +/- 7.4 pg/mL in the exposed group. These results
      indicate that mobile phones, emitting 900 and 1800 MHz EMF, have no effect on
      nocturnal serum melatonin levels in rats.

PMID- 15986575
TI  - Propylene glycol monomethyl ether. A three-generation study of isomer beta
      effects on reproductive and developmental parameters in rats.
AB  - Propylene glycol monomethyl ether (PGME) is widely used as a solvent in numerous
      commercial products. Its chemical synthesis leads to the formation of two
      isomers: alpha and beta, the latter being usually present in the range of 0.5
      1.5%. Isomer alpha has been shown to be of low toxicity. Isomer beta raises
      concerns as to its reproductive and developmental effects. We evaluated the
      reproductive and developmental toxicity of two different commercial mixes of PGME
      (Mix A: 99% isomer alpha and 0.5% isomer beta, Mix B: 98.5% isomer alpha and 1.5%
      isomer beta) on Sprague-Dawley rats. The use of two mixes allowed us to
      differentiate between isomer alpha and isomer beta effects. Male and female rats
      were exposed through drinking water to mixes A or B during a gametogenesis cycle
      (64 days for males and 15 days for females) to 0, 2, 5, 10 and 15% (v/v) of each
      mix. These animals (F0) and the three following generations (F1, F2 and F3) were
      followed. We observed a statistically significant decrease in the number of pups
      in isomer alpha-treated animals of generation F1 and a nondose-related variation
      of the sex ratio in F1 and F2 generations after PGME mix B treatment. The most
      important effect observed was a decrease in testicular and epididymal sperm
      counts in relation to PGME isomer beta in acute daily exposure, on the first
      parental generation. The effect evidenced on sex ratio needs further work in
      order to assay the potential persistent effects of PGME exposure.

PMID- 15986576
TI  - A rat model to evaluate the pesticide permeability and stress effects of
      protective clothing.
AB  - No animal model exists for testing the suitability of a protective garment before
      actual application in humans. The animal testing model is valuable in particular
      as the assessment of permeability of hazardous chemicals in humans cannot be
      easily performed due to possible toxicity to test subjects. We explored a rat
      model by designing a protective garment to fit rats, and then examining pesticide
      permeability and physiological responses. When nongarmented rats were exercised
      in a treadmill, there were increases in heart rate, mean arterial pressure and
      body temperature. The increases in heart rate and body temperature were further
      augmented by wearing the protective garment. Fenitrothion, an organophosphate
      insecticide, was detected in plasma after application on the dorsal area in
      plasma of nongarmented and garmented (comparable to regular human work clothes)
      rats. Plasma acetylcholine esterase activity was decreased, suggesting
      intoxication in these animals. Fenitrothion intoxication was not observed in rats
      wearing a protective garment. In humans, heart rate and body temperature
      augmentation were also observed when wearing a protective garment. This result
      suggests that the present rat model provides a useful assessment of chemical
      permeability and stress effects of protective garments.

PMID- 15986577
TI  - Diffusion flame-derived fine particulate matters doped with iron caused
      genotoxicity in B6C3F1 mice.
AB  - Potential genotoxic effects of diffusion flame-derived particulate matters (PMs),
      known to cause various adverse health problems, doped with iron, one of the
      representative heavy metals frequently found in the atmosphere, were examined.
      B6C3F1 mice were exposed to PMs [chamber 1 (low), 100; chamber 2 (middle), 200;
      and chamber 3 (high), 400 microg/m3] for 6 h/day, 5 days/week for one, two and
      four weeks in 1.5 m3 whole-body inhalation chambers. Our diffusion flame system
      produced 94.8 and 5.2% fine PM2.5 and PM10, respectively, with 89% of PM2.5 sized
      between 0.1 and 0.2 microm. Two cytogenetic endpoints were investigated through
      chromosomal aberration and supravital micronucleus (SMN) assays. Frequencies of
      cells with chromosome aberration (%) were observed in time- and concentration
      dependent manners except in one-week exposure group, as also observed in SMN
      study. Generally, noniron flame induced less chromosome aberration than iron
      doped flame, an indication that iron particles could potentiate urban PM
      toxicity. The above results indicate our diffusion flame system generated
      genotoxic fine PMs, whose effects were potentiated by organometallic particles
      such as iron. Our system can provide reliable PM models for studying the toxicity
      of urban fine PMs applicable for risk assessment.

PMID- 15986578
TI  - The activities of liver adenosine deaminase, xanthine oxidase, catalase,
      superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide
      after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl
      ester.
AB  - The aim of this experimental study was to investigate the effects of caffeic acid
      phenethyl ester (CAPE), an antioxidant agent, on cisplatin-induced hepatotoxicity
      through adenosine deaminase (AD), xanthine oxidase (XO), catalase (CAT),
      superoxide dismutase (SOD) activities and malondialdehyde (MDA) and nitric oxide
      (NO) levels in liver tissue of rats. Wistar albino rats were divided into three
      groups: control group (n = 6), cisplatin group (n = 9) and CAPE + cisplatin group
      (n = 8). All the chemicals used were applied intraperitoneally.
      Spectrophotometric methods were used to determine the activities of the above
      mentioned enzymes in the liver tissue. NO level and XO activity were found to be
      increased in the cisplatin group compared to the control group. NO level was
      found to be decreased in the cisplatin + CAPE group in comparison with the
      cisplatin group. There was no significant change in the activity of XO between
      the cisplatin and cisplatin + CAPE groups. The activity of SOD was lower in the
      cisplatin group than both the control and cisplatin + CAPE groups. There was no
      significant change in the activity of CAT between the control and cisplatin
      groups. CAT activity was increased in the cisplatin + CAPE group compared to the
      cisplatin group. The AD activity and MDA level remained unchanged in all groups.
      The results obtained suggested that CAPE significantly attenuated the
      hepatotoxicity as an indirect target of cisplatin in an animal model of cisplatin
      induced nephrotoxicity.

PMID- 15986580
TI  - [Austrian Society for Internal Medicine and Viennese Clinical magazine/Acta
      medica Austriaca: A fortunate symbiosis].

PMID- 15986579
TI  - Airborne particulates and asthma: a Maine case study.
AB  - Maine currently has the second fastest growing asthma rate in the nation 9.4% of
      the adult population has asthma and one out of eight children is affected. The
      factors behind this increase are poorly understood, but previous reports suggest
      that biologically soluble metal ions from particulate matter (PM10) may play a
      role in asthma episodes. In an effort to study this issue, we first identified
      geographic and temporal trends in Maine asthma hospitalizations. Clinical data
      show a strong fall peak in asthma admissions with weaker peaks in January and
      May, and a summer low in asthma admissions. Asthma admissions are also higher in
      the cities than in the rural areas in Maine. We then analysed PM10 collected by
      the Maine Department of Environmental Protection in three different Maine
      locations in the years 2000 and 2001, at times when clinical asthma data showed
      peaks and during the summer low period. We also collected soil samples in the
      same locations. The PM10 and soils were analysed for 10 metals by acid extraction
      to determine total metal content and then with cell culture medium, DMEM/F12+CCS
      growth medium, to determine metal biosolubility. Our results showed that Mn, Cu,
      Pb, As, V, Ni and Al were present in the Maine PM samples. V, Ni and Pb showed
      seasonal variation, while the others were relatively constant throughout the
      year. Pb and Al did not appear to be soluble in the biological medium. There was
      also variation from location to location with the urban area showing the highest
      concentrations for most metals. Aluminium was present in the highest
      concentration in soil samples, followed by Mn and V. Only Cu was biologically
      available in soils. We determined from M/Al ratios that most of the PM10 did not
      originate from local crustal material.

PMID- 15986581
TI  - [Acta medica Austriaca: a look backwards after forwards].

PMID- 15986582
TI  - [WKW in the year 2005--a further step into the future].

PMID- 15986583
TI  - [Osteoporosis--a neglected disease?].

PMID- 15986584
TI  - [Tumor lysis syndrome: risk factors and treatment].
AB  - Tumor lysis syndrome is a typical oncological complication, characterized by
      hyperuricemia, hyperkalemia, hyperphosphatemia with secondary hypocalcemia,
      acidosis and acute renal failure. it occurs particularly in patients with
      lymphoproliferative diseases during therapy with potent myelosuppressive
      substances. patients with solid tumors rarely develop a tumor lysis syndrome
      during anti-neoplastic therapy (chemo-, hormonal-, steroid therapy,
      radiotherapy). host-related (e.g. pre-existing volume depletion, hyperuricemia,
      acidic urine) and tumor-related (e.g. large tumor burden, tumor sensitivity to
      therapy, advanced stage) risk factors contribute markedly to the development of
      tumor lysis syndrome. prophylaxis and treatment of tumor lysis syndrome consist
      of adequate hydration of the patients (3 l fluid/m2/day) in order to maintain
      urine production of > or =100 ml/h, controlled alkalinisation (urine pH 7.0-7.5)
      and, if necessary, extracorporeal therapy (intermittent or continuous
      hemodialysis or hemodiafiltration). recombinant urate oxidase (rasburicase)
      reduces uric acid values by far more effectively than allopurinol. treatment with
      rasburicase (01.-0.2 mg/kg for 1-7 days) does not only markedly reduce the
      incidence of tumor lysis syndrome in patients with malignancy but also morbidity
      and mortality. hyperphosphate-induced acute renal failure due to intrarenal
      calcium phosphate precipitation may, however, occur even during rasburicase
      therapy

PMID- 15986585
TI  - Giant seminal vesicle cyst.

PMID- 15986586
TI  - Organic hyperinsulinism and endoscopic surgery.
AB  - BACKGROUND: Experience with minimally invasive surgery for organic
      hyperinsulinism is limited. No criteria for patient selection with special regard
      to sporadic, hereditary, multiple and malignant tumors have been defined.
      METHODS: The estimated success rate of endoscopic surgery was retrospectively
      calculated by analysing 34 consecutive patients with organic hyperinsulinism
      operated on by open surgery. A literature search was undertaken to better define
      indications for endoscopic procedures. Differences in postoperative outcome
      (morbidity) between endoscopic and open procedures were analysed. RESULTS: Twenty
      eight of 31 patients (90%) with solitary insulinomas and one of three patients
      with multiple insulinomas were correctly localized preoperatively. Twenty-six
      enucleations (76%) and eight distal resections (24%) including one endoscopic
      tail resection were performed. Theoretically only 14 out of 34 patients (41%)
      would have been suitable for endoscopic surgery (8 enucleations and 6 patients
      for distal resections which were enucleated using an open approach). Pancreatic
      fistulas were documented in three patients (9%). Reviewing 34 publications, 49
      enucleations, 36 distal resections and 15 conversions to open surgery were
      performed, showing a higher proportion of distal resections in endoscopic
      surgery. The spleen was preserved in 88% of cases. Fourteen fistulas occurred
      after enucleations. CONCLUSIONS: Only solitary insulinomas localized in the
      pancreatic tail or superficially in the body or head may be candidates for
      endoscopic procedures. Patients with multiple insulinomas, MEN-1 syndrome or
      malignancy should undergo open surgery.

PMID- 15986587
TI  - Dysfunction of the liver affects the sense of smell.
AB  - BACKGROUND: Cirrhosis of the liver (CL) has been reported to be accompanied by
      olfactory loss. The aim of the present study was to re-investigate previous work
      with a special focus on differential olfactory function, the relation between CL
      etiology and olfactory function, and the correlations between
      laboratory/psychological parameters and olfactory function. MATERIALS AND
      METHODS: A total of 45 CL patients participated. Olfactory function was tested
      using the "Sniffin' Sticks" technique, which provides measures for butanol odor
      thresholds, odor discrimination and odor identification. Serum levels of zinc and
      bilirubin were obtained. Psychometric measurements included the trailmaking test.
      RESULTS: The study provided the following major results: (1) Olfactory function
      was compromised in 76% of CL patients; in addition, the patient's ability to
      identify odors, but not odor thresholds or odor discrimination, was related to
      the degree of CL. This pattern may be an expression of a stronger effect of CL on
      the central- nervous processing of odors than on the periphery of the system. (2)
      Neither etiology of the CL (e.g., alcoholism) nor serum levels of bilirubin and
      zinc were correlated with olfactory function. However, (3) there was a relation
      between the results from psychometric function tests and the ability to identify
      odors. CONCLUSION: Although the reason for olfactory dysfunction in CL is far
      from clear, future investigations should focus on the hypothesis that endogenous
      intoxication may lead to a stronger deficit in the central-nervous processing of
      olfactory information than to peripheral lesions in the olfactory system. In
      addition, while more specific research is needed, olfactory dysfunction may serve
      as a subclinical indicator of hepatic encephalopathy.

PMID- 15986588
TI  - Epidemiology of suicide in Austria 1990-2000: general decrease, but increased
      suicide risk for old men.
AB  - OBJECTIVES AND METHODS: The epidemiology of suicide in Austria, 1990-2000, was
      investigated. RESULTS: In comparison with 1980-1990, an overall decrease in the
      incidence of suicide was found. The annual averages for male, female, and total
      suicide rates were 32.2, 11.0, and 21.3, respectively, representing decreases of
      17.6%, 25.7%, and 19.3%. Decreases were observed in all age groups except for
      males aged 80-84 years, where the suicide rate was 123.5 (15.1% increase), and
      for males aged 85 years or over, where the rate was 148.9 (25.4% increase).
      Hanging is still the most frequently used suicide method in Austria, despite
      steady decreases during recent decades. During the 1990s, hanging was used in
      47.5% of male suicides and 34.8% of female cases. Shooting is the next most
      common method for male suicides (23.5% of cases) and has become more frequent for
      both sexes. CONCLUSIONS: The main findings reveal that the decrease in suicide
      incidence in Austria is greater for females than for males, reflecting the
      increased suicide risk within the oldest male age groups. This population
      subgroup should thus be a particular target for suicide-prevention efforts in
      Austria. A further aim within a national strategy for suicide prevention should
      be to stop the increased use of shooting as a suicide method.

PMID- 15986589
TI  - Schellong test in orthostatic dysregulation: a comparison with tilt-table
      testing.
AB  - OBJECTIVE: To evaluate the role of the Schellong test (ST) in forms of
      orthostatic dysregulation in comparison with the tilt-table test (TT). METHODS:
      67 young males (mean age 22 +/- 4 years) from the military service, representing
      two different cohorts, were examined by ST and TT, which served as gold standard.
      32 of the 67 subjects were asymptomatic while 35 had sought medical advice
      because of orthostatic complaints. The subjects subsequently were classified into
      four categories according to the TT: normal TT, orthostatic hypotension (OH),
      postural orthostatic tachycardia syndrome (POTS), and neurocardiogenic syncope
      (NCS). Chi-square test was used to calculate the sensitivity and specificity of
      ST in detecting forms of orthostatic dysregulation (OH, POTS and NCS). RESULTS:
      In total, TT detected 23 recruits with POTS, 16 with NCS and 2 with OH. Out of
      the 32 asymptomatic subjects only one was diagnosed having POTS by TT and ST, the
      rest had a normal ST and TT. For detecting POTS, ST sensitivity was 61% and
      specificity was 100% compared with TT. For detecting NCS, ST sensitivity was 31%
      and specificity 100% compared with the reference test, the TT. The data
      concerning OH could not be analyzed because of the small number of cases.
      CONCLUSIONS: In conclusion the results of our study indicate that ST can be used
      in first line in the diagnosis of patients with orthostatic symptoms by the
      medical practitioner. If the ST is normal, further examination by TT is
      indispensable, because sensitivity of ST concerning POTS and NCS is relatively
      low.

PMID- 15986590
TI  - Prevalence of vertebral fractures in an urban population in Croatia aged fifty
      and older.
AB  - AIM OF THE STUDY: To establish the prevalence of vertebral fractures according to
      age groups, sex and vertebral level in a sample of a Croatian urban population
      aged > or =50. We also tried to establish how many people had been diagnosed with
      osteoporosis by their family physician. PARTICIPANTS AND METHODS: Lateral
      thoracic and lumbar spinal radiographs were obtained in 425 ambulatory people
      (156 men and 269 women) aged > or =50 and living in the community as a random
      sample of the City of Zagreb (Croatia) population. An interviewer-administered
      questionnaire was used to obtain information on prior traumatic vertebral
      fractures and whether the person had been diagnosed with osteoporosis. Vertebral
      fractures in the population sample were defined using the morphometric method
      proposed by McCloskey et al., and normal values of the ratios of dimensions in
      nonfractured vertebrae with the iterative algorithm described by Melton et al.
      RESULTS: The prevalence of individuals with vertebral fractures was 11.8% (15.8%
      of men and 9.7% of women), ranking Zagreb mid-scale among other European cities.
      The prevalence of individuals with vertebral fractures rose with age. Sixty-nine
      (1.24%) of 5525 analysed vertebrae had been fractured. The most common fractures
      were those of lower thoracic and upper lumbar vertebrae. The elderly tend to
      sustain multiple fractures. Forty-one (9.6%) people had been previously diagnosed
      as having osteoporosis. Extrapolation to the Croatian population implies that
      approximately 90,000 men and 77,000 women aged > or =50 have vertebral fractures.
      CONCLUSION: Vertebral osteoporotic fractures are common in the Croatian
      population aged > or =50; however, awareness of osteoporosis appears to be low.

PMID- 15986591
TI  - Preoperative second-line chemotherapy induces objective responses in primary
      breast cancer.
AB  - PURPOSE: Preoperative chemotherapy in patients with primary breast cancer results
      in high response rates, allowing breast-conserving surgery in patients primarily
      not suitable for this procedure. Tumors of patients with histologically proven
      breast cancer that fail to respond to preoperative chemotherapy are thought to be
      chemotherapy resistant. We questioned this hypothesis and treated 13 patients who
      did not respond to preoperative anthracycline-containing first-line treatment.
      PATIENTS AND METHODS: Eight patients received a combination therapy consisting of
      epidoxorubicin and docetaxel as neoadjuvant first-line treatment and were treated
      with CMF as preoperative second-line chemotherapy. The other five patients did
      not respond to first-line FEC and were given paclitaxel or docetaxel as second
      line treatment. RESULTS: A major response to treatment was observed in 10 of 13
      patients (77%) during preoperative second-line therapy: one patient (8%) achieved
      pathological complete response (pCR) and nine patients (69%) partial response
      (PR). Three patients (23%) had stable disease (SD), and no patient had
      progressive disease (PD). Eight patients (62%) could undergo breast-conserving
      surgery. CONCLUSIONS: We conclude that it is possible to achieve objective
      responses including pCR with potentially non-cross-resistant neoadjuvant second
      line therapy, leading to breast-conserving surgery in a high proportion of
      patients. Thus, preoperative second-line chemotherapy appears to be justified
      when breast conservation is an important treatment goal and may have potential in
      improved tailoring of neoadjuvant treatments.

PMID- 15986592
TI  - Quantitation of microvessel density in squamous cell carcinoma of the head and
      neck by computer-aided image analysis.
AB  - OBJECTIVE: Angiogenesis is the formation of new blood vessels from a preexisting
      vascular network. In healthy individuals it is normally suppressed and observed
      only transiently during development, reproduction and wound healing. However,
      growth, invasion, and metastasis of most solid tumors are dependent on
      angiogenesis. Without formation of new blood vessels, also termed as
      neovascularization, tumors cannot exceed a size of about 1 mm3. Therefore,
      neovascularization is a basic requirement for nutrition and oxygenation of tumor
      cells. Numerous studies in different solid as well as non-solid tumors have
      evaluated the prognostic value of tumor neovascularization. In solid tumors the
      increased microvessel density, the pathological correlate to tumor
      neovascularization, has been linked to a worse prognosis of the disease. The aim
      of the current study was to assess the prognostic value of tumor
      neovascularization for recurrences in squamous cell carcinoma of the head and
      neck by determining microvessel density. Data was collected using an automated
      computerized method and as well as a manual counting method. BASIC RESEARCH
      DESIGN: Immunohistochemistry was performed to detect intratumoral microvessels in
      tumor samples of 50 patients with squamous cell carcinoma of the head and neck.
      We used a monoclonal mouse antibody directed against the CD34 antigen. After
      immunostaining, the entire tumor section was scanned microscopically at low power
      (x 40) to identify hot spots, which are the areas of highest neovascularization.
      Individual tumor microvessels were then counted under high power (x 200) to
      obtain a vessel count in a defined area, and the average vessel count in 4 hot
      spots was taken as the microvessel density. Microvessel counting was performed
      twice by computerized method, as well as manually by two independent
      investigators without any previous knowledge of patients' pertinent clinical
      data. Subsequently, both counting techniques were statistically compared with
      each other. RESULTS: On computer-aided image analysis an increased microvessel
      density was significantly correlated with recurrence of disease (p = 0.02).
      Repetitive computer counts yielded similar results (p = 0.08), whereas repeated
      manual counts by two investigators varied significantly (p = 0.04). However, no
      further statistical correlations between microvessel density and patients
      clinical data i.e. tumor status, lymph node status, overall survival, or disease
      free interval could be found. Furthermore, estimation of overall survival of
      patients with an increased microvessel density by Kaplan-Meier curves revealed
      non-significant results. CONCLUSION: There is mounting evidence that suggests,
      that assessment of tumor neovascularization might provide a novel approach of
      prognostication in patients with squamous cell carcinomas of the head and neck.
      In particular, in the present study, the degree of angiogenesis of a tumor, as
      assessed by microvessel density, was found to be correlated with recurrent
      disease in squamous cell carcinoma of the head and neck. Computer aided image
      analysis, an automated technique, constitutes a time-efficient and reproducible
      technique for quantification of tumor vascularization. We suggest that this
      computerized microvessel determination could be used as a reliable method for
      microvessel counts, which, furthermore, seems to be superior to manual counting.
      However, for a reliable and reproducible assessment of tumor neovascularization,
      validation procedures and quality control protocols are mandatory.

PMID- 15986593
TI  - Congenital absence of the portal vein in an adult woman: a case report.
AB  - Congenital absence of the portal vein is a rare malformation. Mesenteric and
      splenic venous blood bypasses the liver and drains into the renal veins or
      directly into the inferior vena cava. The malformation occurs predominantly in
      females and children and is often associated with other anomalies such as hepatic
      tumors, cardiac malformations and skeletal abnormalities. We describe a 23-year
      old female with congenital absence of the portal vein associated with variant
      origin of the hepatic artery from the superior mesenteric artery. Additional
      anomalies were not present. The patient is in good condition. Laboratory tests
      showed elevated total bilirubin; other liver parameters were within normal range.
      The absence of the portal vein was confirmed by MR angiography, which revealed
      that the upper part of the superior mesenteric vein and the splenic vein drained
      into the left renal vein. A liver biopsy showed no signs of cirrhosis. Yearly
      follow-up with laboratory tests and ultrasonography was recommended to our
      patient. According to the literature, the prognosis of this patient depends on
      the presence of cardiac defects and liver tumors. There is little information on
      the outcome of patients with congenital absence of the portal vein; only long
      term follow-up investigations will provide answers to the numerous remaining
      questions.

PMID- 15986595
TI  - Properties of crowding indices and statistical tools to analyze parasite crowding
      data.
AB  - Crowding, i.e., the size of the infrapopulation inhabiting an individual host, is
      a major component of parasites' environment, which often influences both
      morphological and life-history characters (the so-called density-dependent
      characters) in different parasite taxa. Although crowding equals intensity in
      case of a single parasite individual, mean intensity of the host population does
      not define mean crowding of the parasite population. Crowding indices are
      notoriously hard to handle statistically because of the inherently large number
      of nonindependent values in data. In this study, we aim to investigate the
      apparently paradox features of crowding indices and to make some proposals and
      also to introduce statistical methods to calculate confidence intervals and 1
      sample and 2-sample tests for mean crowding. All methods described in this study
      are supported by the freely distributed statistical software Quantitative
      Parasitology.

PMID- 15986594
TI  - Major response and clinical benefit following third-line treatment for Bellini
      duct carcinoma.
AB  - Bellini duct carcinoma accounts for 1-3% of all renal carcinomas and is
      characterized by an aggressive course and extremely poor prognosis. Conventional
      treatment for renal-cell carcinoma seems to be ineffective. Since the histology
      of Bellini duct carcinoma is similar to urothelial carcinoma, chemotherapy for
      urothelial cancer might be more promising than conventional treatment. We present
      a patient with renal carcinoma of the left kidney who underwent laparoscopic
      extrafascial nephrectomy and adrenalectomy. Histopathologic work-up showed
      Bellini duct carcinoma (pT3a, NX, G3, R0 and M0). Eight months after surgery,
      disease progression was observed with local recurrence, multiple pulmonal
      lesions, para-aortic and aortocaval lymphadenopathies and a solitary bone lesion.
      First-line treatment with interferon-alpha and interleukin-2, as well as second
      line treatment with thalidomide, were ineffective. Disease progressed rapidly and
      the patient experienced a dramatic reduction in performance status and quality of
      life. Six courses of chemotherapy with cisplatin and gemcitabine were given, a
      treatment reported to be highly active in urothelial cancer. The treatment was
      well tolerated, with thrombopenia WHO grade II, anemia WHO grade I and
      nausea/vomitus WHO grade II being the most severe side effects. Follow-up
      computer tomography revealed partial remission with 50-100% response at the
      different sites of metastasis. This response was accompanied by a dramatic
      improvement in performance status (from an initial 60% to 100% Karnofsky index)
      and quality of life. The combination of cisplatin and gemcitabine was highly
      active in this patient with metastatic Bellini duct carcinoma, even given as
      third-line treatment. This regimen fulfils all criteria for palliative treatment,
      as our patient showed an impressive improvement in WHO performance status and
      therefore in quality of life. Histopathologic characteristics should be a major
      criterion for treatment strategy in renal carcinoma, particularly in Bellini duct
      carcinoma.

PMID- 15986596
TI  - Phylogeny of species of Sciadicleithrum (Monogenoidea: Ancyrocephalinae), and
      their historical biogeography in the neotropics.
AB  - The phylogenetic relationships and historical biogeography of species of
      Sciadicleithrum parasitizing Neotropical cichlid fishes were studied. Hypotheses
      were: Did the presence of Sciadicleithrum species in southeast Mexico (SM) and
      Central America (CA) result from early dispersal of cichlid species from South
      America (SA) to the north via the Antilles during the Tertiary (24 million years
      ago [mya]), or did it occur after emergence of the Panama Isthmus in the
      Pleistocene (2-5 mya)? The Sciadicleithrum phylogeny was based on 19
      morphological transformation series, with species of Gussevia and Cichlidogyrus
      as outgroups. The most parsimonious cladogram had a 40% consistency index, with
      one clade including all the species of Sciadicleithrum from SA and all but one of
      those from CA and another with all the Sciadicleithrum species from SM and S.
      maculicaudae from CA. Results support the late dispersal hypothesis following
      emergence of the Panama Isthmus. Fifteen species of Sciadicleithrum parasitize 13
      cichlid species from SA and CA. In contrast, only 4 species of Sciadicleithrum
      infect 14 cichlid species from SM. Parasite speciation appears to lag behind host
      speciation, with 2 equally possible explanations: loss of parasite species and
      host switching.

PMID- 15986597
TI  - Sequence variation of the ribosomal DNA second internal transcribed spacer region
      in two spatially-distinct populations of Amblyomma americanum (L.) (Acari:
      Ixodidae).
AB  - Sequence analysis of the ribosomal DNA second internal transcribed spacer (ITS 2)
      region in 2 spatially distinct populations of Amblyomma americanum (L.) revealed
      intraspecific variation. Nucleotide sequences from multiple DNA extractions and
      several polymerase chain reaction amplifications of eggs from mixed-parentage
      samples from both populations of ticks revealed that 12 of 1,145 (1.0%) sites
      varied. Three of the 12 sites of variation were distinct between the 2 A.
      americanum populations, which corresponded to a rate of 0.26%. Phylogenetic
      analysis based on ITS 2 sequences provided strong support (i.e., bootstrap value
      of 80%) that wild A. americanum clustered into a distinguishable group separate
      from those derived from colony ticks.

PMID- 15986598
TI  - Kinetics of T cell cytokine gene expression in gerbils after a primary
      subcutaneous Brugia pahangi infection.
AB  - The majority of patients infected with lymphatic filariae are microfilaremic but
      tend to manifest little obvious pathology because of the infections. Data
      collected from the Mongolian gerbil-Brugia spp. model for human lymphatic
      filariasis suggest this experimental animal model system most closely represents
      this patient group and will be useful in studying immunological parameters
      associated with chronic infections. This article reports the quantitation of
      interleukin (IL)-4, IL-5, IL-10, IL-13, and interferon (IFN)-gamma messenger RNA
      (mRNA) in gerbils after a primary subcutaneous infection with Brugia pahangi.
      Chronically infected gerbils showed elevated IL-4 in all tissues, compared with
      earlier time points, linking this Th2 cytokine to the downregulation of
      responsiveness, which develops in gerbils and humans. Both IL-5 and IL-13 mRNA
      expression were transient in all tissues. The peak in IL-5 at 14-28 days
      postinfection reflects the peak of peripheral eosinophilia observed in B. pahangi
      infected gerbils. Little IFN-gamma mRNA was reported from chronically infected
      gerbils. The data collected thus far suggest that the expression profile of many
      of the measured cytokines in B. pahangi-infected gerbils reflects what is seen in
      an important subset of humans infected with lymphatic filariae, the
      microfilaremic, asymptomatic patient.

PMID- 15986599
TI  - Influence of phospholipid composition on the adjuvanticity and protective
      efficacy of liposome-encapsulated Leishmania donovani antigens.
AB  - In this study, we evaluate the effect of phospholipid on the adjuvanicity and
      protective efficacy of liposome vaccine carriers against visceral leishmaniasis
      (VL) in a hamster model. Liposomes prepared with distearyol derivative of L-alpha
      phosphatidyl choline (DSPC) having liquid crystalline transition temperature (Tc)
      54 C were as efficient as dipalmitoyl (DPPC) (Tc 41 C) and dimyristoyl (DMPC) (Tc
      23 C) derivatives in their ability to entrap Leishmania donovani membrane
      antigens (LAg) and to potentiate strong antigen-specific antibody responses.
      However, whereas LAg in DPPC and DMPC liposomes stimulated inconsistent delayed
      type hypersensitivity (DTH) responses, strong DTH was observed with LAg in DSPC
      liposomes. The heightened adjuvant activity of DSPC liposomes corresponded with
      95% protection, with almost no protectivity with LAg in DPPC and DMPC liposomes,
      4 mo after challenge with L. donovani. These data demonstrate the superiority of
      DSPC liposomes for formulation of L. donovani vaccine. In addition, they
      demonstrate a correlation of humoral and cell-mediated immunity with protection
      against VL in hamsters.

PMID- 15986600
TI  - Respiratory burst of Biomphalaria glabrata hemocytes: Schistosoma mansoni
      resistant snails produce more extracellular H2O2 than susceptible snails.
AB  - The production of reactive oxygen species by hemocytes from the gastropod
      Biomphalaria glabrata has been linked to their ability to kill the trematode
      parasite Schistosoma mansoni. For 2 laboratory strains of the snail, 1 resistant
      (13-16-R1) and 1 susceptible (MO) to the PR1 strain of S. mansoni, we compared
      hemocyte production of extracellular hydrogen peroxide when stimulated with the
      protein kinase C agonist phorbol myristate acetate (PMA). The time course of the
      PMA-induced response is similar in both strains with respect to onset, peak
      production, and termination of the respiratory burst. However, the magnitude of
      the response differs between strains, in that hemocytes from resistant snails
      generate significantly more hydrogen peroxide. These findings suggest that the
      capacity to produce hydrogen peroxide could be critical in determining
      susceptibility or resistance to S. mansoni.

PMID- 15986601
TI  - Studies on two strains of Plasmodium cynomolgi in New World and Old World monkeys
      and mosquitoes.
AB  - Infections that cause the Gombak and Smithsonian strains of Plasmodium cynomolgi
      were induced in Macaca mulatta, Aotus lemurinus griseimembra, Aotus nancymai, and
      Saimiri boliviensis monkeys. Transmission of the Gombak strain to Aotus spp.
      monkeys was obtained by the injection of sporozoites dissected from the salivary
      glands of experimentally infected Anopheles dirus and by the bites of infected
      An. dirus and Anopheles farauti mosquitoes. Two S. boliviensis monkeys were
      infected via the injection of sporozoites dissected from An. dirus. Prepatent
      periods in New World monkeys ranged from 14 to 44 days, with a median of 18 days.
      The Smithsonian strain was transmitted via sporozoites to 1 A. lemurinus
      griseimembra and 9 A. nancymai monkeys. Prepatent periods ranged from 12 to 31
      days.

PMID- 15986602
TI  - Binding properties and immunolocalization of a fatty acid-binding protein in
      Giardia lamblia.
AB  - We describe here a fatty acid-binding protein (FABP) isolated and purified from
      the parasitic protozoon Giardia lamblia. The protein has a molecular mass of 8
      kDa and an isoelectric point of 4.96. A Scatchard analysis of the data at
      equilibrium revealed a dissociation constant of 3.12 x 10(-8) M when the labeled
      oleic acid was displaced by a 10-fold greater concentration of unlabeled oleic
      acid. Testosterone, sodium desoxycholate, taurocholate, metronidazol, and alpha
      tocopherol, together with butyric, arachidonic, palmitic, retinoic, and
      glycocholic acids, were also bound to the protein. Assays with polyclonal
      antibodies revealed that the protein is located in the ventral disk and also
      appears in the dorsal membrane, the cytoplasm, and in the vicinity of the lipid
      vacuoles.

PMID- 15986603
TI  - Molecular cloning and characterization of copper/zinc-superoxide dismutase of
      Paragonimus westermani.
AB  - Superoxide dismutases (SODs; EC 1.15.1.1) play important roles in the protection
      of the parasites against cellular oxygen-mediated killing of the hosts. A
      copper/zinc-containing SOD (Cu/Zn-SOD) was identified previously from lung fluke,
      Paragonimus westermani. To expand our understanding of P. westermani SOD, we
      isolated a complementary DNA encoding a Cu/Zn-SOD, expressed the active enzyme in
      Escherichia coli, and characterized its biochemical properties. The deduced amino
      acid (aa) sequence of the gene shared up to 73.7% identities with Cu/Zn-SODs of
      other helminths and shared well-conserved characteristic motifs and essential aa
      residues involved in coordinating copper and zinc enzymatic functions.
      Recombinant Cu/ Zn-SOD exhibited comparable biochemical properties with that of
      the native enzyme, including pH optima and potassium cyanide-and hydrogen
      peroxide-sensitive inhibition profiles. The active enzyme consisted of 2
      identical subunits covalently linked by disulfide bonds. The enzyme was
      constitutively expressed throughout various developmental stages of the parasite.
      The levels increased as P. westermani matured and plateaued in adult stage. Our
      result suggests the enzyme might play an important role for parasites to survive
      in the hosts through its superoxide anion-detoxifying function.

PMID- 15986605
TI  - Differential effects of interferon-gamma and tumor necrosis factor-alpha on
      Toxoplasma gondii proliferation in organotypic rat brain slice cultures.
AB  - Organotypic slice culture explants of rat cortical tissue infected with
      Toxoplasma gondii tachyzoites were applied as an in vitro model to investigate
      host-pathogen interactions in cerebral toxoplasmosis. The kinetics of parasite
      proliferation and the effects of interferon-gamma (IFN-gamma) and tumor necrosis
      factor-alpha (TNF-alpha) in infected organotypic cultures were monitored by light
      microscopy, transmission electron microscopy (TEM), and quantitative polymerase
      chain reaction (PCR) assay. As assessed by the loss of the structural integrity
      of the glial fibrillary acidic protein-intermediate filament network, tachyzoites
      infected and proliferated mainly within astrocytes, whereas neurons and microglia
      remained largely unaffected. Toxoplasma gondii proliferation was severely
      inhibited by IFN-y. However, this inhibition was not linked to tachyzoite-to
      bradyzoite stage conversion. In contrast, TNF-alpha treatment resulted in a
      dramatically enhanced proliferation rate of the parasite. The cellular integrity
      in IFN-gamma-treated organotypic slice cultures was severely impaired compared
      with untreated and TNF-alpha-treated cultures. Thus, on infection of organotypic
      neuronal cultures, IFN-gamma and TNF-alpha exhibit largely detrimental effects,
      which could contribute to either inhibition or acceleration of parasite
      proliferation during cerebral toxoplasmosis.

PMID- 15986604
TI  - Heat shock protein 90 genes of two species of poultry Eimeria: expression and
      evolutionary analysis.
AB  - Heat shock protein 90 (Hsp90) is 1 of the most abundant and evolutionarily
      conserved proteins. In most species, Hsp90 is essential for proper cell function.
      In this study, we present the molecular analysis of Hsp90 from Eimeria species,
      the causative agents of avian coccidiosis. The full-length Eimeria acervulina
      Hsp90 complementary DNA was isolated from intestinal intraepithelial lymphocytes
      of Eimeria-infected chickens. From evolutionary analysis and sequence identity,
      it is likely that Eimeria Hsp90 sequences described thus far encode the cytosolic
      versions of the protein. Although at the nucleotide and amino acid levels Eimeria
      tenella and E. acervulina Hsp90 are highly similar, their expression profiles
      differ considerably. Although E. tenella transcripts were detected in all
      developmental stages tested, E. acervulina transcripts were not found in oocysts
      undergoing sporulation or in fully sporulated oocysts, suggesting that messenger
      RNA expression may be regulated quite differently between Eimeria species.

PMID- 15986606
TI  - Ex vivo and in vitro impairment of CD36 expression and tumor necrosis factor
      alpha production in human monocytes in response to Plasmodium falciparum
      parasitized erythrocytes.
AB  - Severe malaria is associated with the failure of host defenses to control
      parasite replication, with the excessive secretion of proinflammatory cytokines
      such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of
      parasitized erythrocytes (PEs) in the microcirculation of vital organs. The
      scavenger receptor CD36, known as a major sequestration receptor, has also been
      identified as an important factor in mediating nonopsonic phagocytosis of PEs by
      monocytes and macrophages. The specific consequence of this phagocytosis is a
      decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in
      CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in
      monocytes from Plasmodium falciparum-infected patients and in vitro in the
      presence of PEs. Both the monocytes from infected patients and from in vitro
      culture showed a decrease of CD36 expression and a reduced production of TNF
      alpha induced by LPS. Using incubation assays with no contact between monocytes
      and PEs, or in the presence of a soluble supernatant obtained from the incubation
      of monocytes and PEs, this study shows that decreased CD36 expression was
      posttranscriptional and not directly related to PEs phagocytosis. In addition,
      these culture models suggest that the reduced capacity of TNF-alpha production
      occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and
      the second phase (48 hr) was due to a soluble factor produced by PEs. These
      observations suggest that the control of the TNF-alpha production in malaria by
      monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that
      soluble factors produced by PEs could play a role in this process.

PMID- 15986607
TI  - New species of Spauligodon (Nematoda: Pharyngodonidae) in Lepidodactylus
      novaeguineae (Sauria: Gekkonidae) from Papua New Guinea.
AB  - Spauligodon zweifeli n. sp. (Nematoda: Pharyngodonidae) from the large intestines
      of a gecko, Lepidodactylus novaeguineae (Sauria: Gekkonidae), is described and
      illustrated. Prevalence of infection was 57% (mean intensity 8.5, range 1-23).
      Spauligodon zweifeli n. sp. is the 43rd species to be assigned to this genus and
      differs from other species in the genus by possessing asymmetrical fusiform eggs
      in which the ends are extended as digitiform processes. It is the second species
      to be described from the Australian biogeographical realm.

PMID- 15986608
TI  - A new species of Vexillata (Nematoda: Trichostrongylina: Ornithostrongylidae)
      parasite of Heteromys desmarestianus (Rodentia: Heteromyidae) from Costa Rica.
AB  - In July 1999, 2 heteromyid rodents Heteromys desmarestianus Gray, 1868, were
      collected from the Area de Conservacion Guanacaste, Costa Rica, and examined for
      parasites. Individuals of a new species of Vexillata (Travassos, 1937) Durette
      Desset, 1970, were found from the intestine of hosts. Vexillata brooksi n. sp.
      differs from all other congeners by the presence of spicules divided at the tip
      instead of simple spicules. The new species closely resembles Vexillata legallae
      Denke, 1977, and Vexillata convoluta (Caballero and Cerecero, 1943); however, it
      can be distinguished from both species by possessing a smaller number of
      cuticular ridges at the posterior part of the body in males (9 vs. 11 and 12,
      respectively) and by the absence of a carene at this level.

PMID- 15986609
TI  - A new cystidicolid nematode from Mullus surmuletus (Perciformes: Mullidae) from
      the western Mediterranean.
AB  - Ascarophis valentina n. sp. is described from Mullus surmuletus off the Valencian
      coast of Spain on the basis of both light and scanning electron microscopy. It
      can be distinguished from the other members of the genus by the length of the
      left (long) spicule of the males and by egg morphology. An updated grouping of
      the species of Ascarophis considered valid is provided with respect to these
      characters. The new species resembles Ascarophis capelanus, belonging to the
      group of species possessing eggs with a single polar knob with filaments, but is
      distinguished by the size of the body, the length of the esophagus (especially in
      relation to body length), the position of the vulva, and the size of the left
      spicule. The new species also shows substantial morphological differences
      compared with the 3 species, Ascarophis mullusi, Ascarophis upenei, and
      Ascarophis parupenei, previously described from mullid hosts.

PMID- 15986610
TI  - Molecular phylogeny of Corynosoma Luhe, 1904 (Acanthocephala), based on 5.8S and
      internal transcribed spacer sequences.
AB  - Species of Corynosoma (Acanthocephala) are distributed worldwide as parasites of
      marine mammals and sea birds. Species diagnosis is based on morphological
      characters, including the size and number of hooks in the proboscis and the
      number of spines in the dorsal and ventral regions of the body. We inferred the
      phylogenetic relationships of 10 nominal species of Corynosoma through analysis
      of internal transcribed spacers (ITS-1, ITS-2) and 5.8S ribosomal RNA sequences.
      Nucleotide distances between species of Corynosoma ranged from 0.4 to 11% for ITS
      sequences. Maximum parsimony and likelihood analyses indicated that species of
      Corynosoma that inhabit hosts in the marine environment form a monophyletic
      assemblage, but yielded conflicting hypotheses for the relationship of Corynosoma
      cetaceum to other members of the genus. However, parsimony and likelihood
      analyses were consistent for many Corynosoma sister species relationships of
      (e.g., C. australe plus C. bullosum, C. validum plus C. villosum, C. caspicum
      plus C. magdaleni, and C. enhydri plus C. strumosum). This phylogenetic framework
      was used to evaluate taxonomic controversies concerning C. cetaceum and C.
      caspicum.

PMID- 15986611
TI  - Description of a new Eimeria species and redescription of Eimeria mayeri
      (Protozoa: Eimeriidae) from wild reindeer Rangifer tarandus in Iceland.
AB  - Altogether, 195 fecal samples of reindeer calves (Rangifer tarandus) were
      collected from the ground in 3 distinct areas in eastern Iceland, where
      geographically isolated reindeer populations graze during the summer months. The
      samples were examined for coccidian parasites. Two species were found, and all
      infections were monospecific. Eimeria mayeri was found in calves in all sampling
      areas, with 1-4% prevalence and 450-167,700 oocysts per gram (opg). The
      sporulated oocyst lacks a polar granule but has an inconspicuous micropyle, and a
      small Stieda body is present on sporocysts, which are ovoid but not pointed as
      reported in the original description. The other coccidian, found in single calves
      in 2 of the 3 areas (prevalence 1 and 4%, 150 and 500 opg, respectively) is
      described here as a new species. The oocysts are ovoid, average 34.9 x 27.6
      microm, and have 2 distinct walls. Wall thickness is approximately 1.9 microm,
      and the outer wall, approximately 3/4 of total thickness, is generally smooth and
      appears bicolored. The outermost portion is pale red and the innermost portion
      yellow to pale brown. The inner wall is grey to dark brown and separated from the
      outer wall by a dark brown line. Oocysts contain a prominent micropyle,
      approximately 5 microm, and enclose 4 spindle-shaped sporocysts, slightly pointed
      at the end opposite the Stieda body. Average size of sporocysts is 18.6 x 9.2
      microm. Sporocysts contain granular sporocyst residuum and usually 2, sometimes
      1, large refractile bodies in each sporozoite.

PMID- 15986612
TI  - Coevolution and biogeography among Nematodirinae (Nematoda: Trichostrongylina)
      Lagomorpha and Artiodactyla (Mammalia): exploring determinants of history and
      structure for the northern fauna across the holarctic.
AB  - Nematodes of the subfamily Nematodirinae are characteristic components of a
      Holarctic fauna. The topology of a generic-level phylogenetic hypothesis,
      patterns of diversity, and geographic distributions for respective nematode taxa
      in conjunction with data for host occurrence are consistent with primary
      distributions determined across Beringia for species of Murielus, Rauschia,
      Nematodirus, and Nematodirella. Ancestral hosts are represented by Lagomorpha,
      with evidence for a minimum of 1 host-switching-event and subsequent radiation in
      the Artiodactyla. Diversification may reflect vicariance of respective faunas
      along with episodic or cyclical range expansion and isolation across Beringia
      during the late Tertiary and Quaternary. Secondarily, species of Nematodirus
      attained a distribution in the Neotropical region with minimal diversification of
      an endemic fauna represented by Nematodirus molini among tayassuids, Nematodirus
      lamae among camelids and Nematodirus urichi in cervids during the Pleistocene.
      Nematodirines are a core component of an Arctic-Boreal fauna of zooparasitic
      nematodes (defined by latitude and altitude) adapted to transmission in extreme
      environments characterized by seasonally low temperatures and varying degrees of
      desiccation. The history and distribution of this fauna is examined in the
      context of biotic and abiotic determinants for geographic colonization and host
      switching with an exploration of predicted responses of complex host-parasite
      systems to ecological perturbation under a regime of global climate change.

PMID- 15986613
TI  - Pseudostertagia bullosa (Nematoda: Trichostrongyloidea) in artiodactyl hosts from
      North America: redescription and comments on systematics.
AB  - A relationship for Pseudostertagia bullosa within the trichostrongyloids has been
      enigmatic or unresolved. Studies of the synlophe in males and females of P.
      bullosa revealed a tapering system anterior to the deirids and a pattern of
      parallel ridges extending to near the caudal extremity in both lateral and median
      fields. Structurally, the synlophe differs considerably from that seen among the
      Cooperiinae and exhibits homoplasy with respect to ridge systems among some
      Ostertagiinae. Other structural characters due to symplesiomorphy, homoplasy or
      because they represent autapomorphies do not serve to reveal the putative
      relationships for P. bullosa with other trichostrongyloids. Although somewhat
      equivocal, the 2-2-1 pattern of the bursa and position of rays 2 and 3 suggest an
      association with the Cooperinae, as postulated by Durette-Desset and others.
      Pseudostertagia bullosa appears to be a species that has survived in the
      pronghorn, Antilocapra americana, a relictual pecoran artiodactyl that occurs in
      xeric regions of western North America; pronghorn are the sole remnant of the
      late Tertiary radiation for Antilocapridae across North America. Pseudostertagia
      bullosa may occur in mixed infections with a number of ostertagiines in the
      abomasa of mule deer (Odocoileus hemionus) and domestic sheep (Ovis aries) in
      regions of sympatry for pronghorn and these artiodactyl hosts.

PMID- 15986614
TI  - Phylogeny for genera of Nematodirinae (Nematoda: Trichostrongylina).
AB  - Monophyly for the Nematodirinae, with 5 genera, Murielus, Rauschia,
      Nematodiroides, Nematodirus, and Nematodirella was confirmed based on comparative
      morphology and phylogenetic analysis of structural characters. This concept for
      the nematodirines excludes the monotypic Lamanema chavezi, but otherwise
      corroborates generic-level diversity as defined in prior studies. Exhaustive
      analysis resulted in 1 most parsimonious tree (36 steps; consistency index [CI] =
      0.94; retention index [RI] = 0.93; excluding phylogenetically uninformative
      characters, CI = 0.92). As an inclusive or monophyletic group, Nematodirinae was
      diagnosed by 8 synapomorphies (7 are unequivocal): (1) large eggs, (2) long
      filiform spicules, (3) basal division of the dorsal ray, (4) symmetrical membrane
      enveloping the spicule tips, (5) fused structure of the spicule tips, (6) absence
      of the gubernaculum, (7) development of the third-stage larva within the egg, and
      (8) ornamentation in the form of discrete bosses on the bursa. Exclusion of
      Lamanema will require new assessments of historical biogeography and the
      evolution of host associations for the nematodirines.

PMID- 15986615
TI  - Leucocytozoon (Apicomplexa: Leucocytozoidae) from West African birds, with
      descriptions of two species.
AB  - Five species of Leucocytozoon were recovered from 35/828 birds of 95 species
      examined from 6 sites in West Africa between May 1995 and June 2001.
      Leucocytozoon pogoniuli n. sp. is described from the tinker barbets Pogoniulus
      subsulphureus and Pogoniulus atroflavus. Leucocytozoon trachyphoni n. sp. is
      described from the barbet Trachyphonus purpureus. No leucocytozoids have been
      reported previously in species of Pogoniulus. Leucocytozoon nectariniae was
      identified from the sunbird Nectarinia olivacea, and Leucocytozoon brimonti was
      recovered from 4 species of Pycnonotidae (bulbuls), all of which are new host
      records. We also report the first Leucocytozoon to be recovered from the
      phylogenetically isolated bird, Picathartes sp. (Picathartidae). This parasite is
      similar in appearance to Leucocytozoon sakharoffi, and probably represents a
      previously undescribed species. In view of the intraspecific variability and,
      frequently, relatively minor interspecific differences within Leucocytozoidae, we
      suggest that the development and application of molecular techniques would
      greatly advance understanding of speciation and relationships within this family.

PMID- 15986616
TI  - Species of Gorgoderina (Digenea: Gorgoderidae) in Rana vaillanti and Rana cf.
      forreri (Anura: Ranidae) from Guanacaste, Costa Rica, including a description of
      a new species.
AB  - Gorgoderina parvicava, G. diaster, and G. megacetabularis n. sp. are reported
      inhabiting the urinary bladders of Rana vaillanti and R. cf. forreri from
      northwestern Costa Rica. Gorgoderina megacetabularis n. sp. differs from all
      other species of the genus by the combination of the following characters: small
      body size (2.78-3.17, mean 2.92 mm), sucker ratio (1:3.1-3.7), and by the
      presence of 2 compact, oval, unlobed vitelline masses. Redescription of G.
      diaster including previously undescribed details on the reproductive apparatus
      and morphometric data is provided. This is the first record of the 3 species of
      Gorgoderina in Costa Rica and is the first record of G. diaster in R. vaillanti
      and R. cf. forreri.

PMID- 15986617
TI  - A new trichosomoidid from the skin of Sebastes spp. (Pisces) from British
      Columbia, Canada.
AB  - A new species of trichosomoidid nematode, Huffinanela canadensis n. sp., is
      described from the skin of rockfish (Sebastes spp.) from the Pacific Ocean off
      the coast of Vancouver Island (Clayoquot Sound region), British Columbia, Canada,
      on the basis of the morphology of the adult worms and their eggs in the host's
      tissue and the biological characters. The species is characterized mainly by the
      shape and structure of the fully developed eggs (absence of surface envelope,
      surface with transverse ridges), by their small size (48-63 x 24-27 microm), and
      by the site of infection (skin). Besides Huffmanela huffmani, this is the second
      Huffmanela species in which adult worms are known in addition to the eggs from
      the host's tissues (most Huffmanela spp. have been described only from their
      conspicuous eggs occurring in various tissues of fishes). Adults of H. canadensis
      differ morphologically from those of H. huffmani, mainly in the structure of the
      male caudal end and in the distinctly elevated anterior vulvar lip of the female.

PMID- 15986618
TI  - Observations on two Rhabdochona species (Nematoda: Rhabdochonidae) from
      freshwater fishes in Argentina, including description of Rhabdochona fabianae n.
      sp.
AB  - Helminthological examination of specimens of the freshwater fishes Bryconamericus
      iheringi Boulenger, 1887 (Characidae) and Jenynsia multidentata (Jenyns, 1842)
      (Anablepidae), collected from Medina River, Province of Tucuman, Argentina,
      revealed the presence of 2 species of parasitic nematodes, Rhabdochona fabianae
      n. sp. and Rhabdochona acuminata (Molin, 1860) (Rhabdochonidae). Rhabdochona
      fabianae n. sp. was characterized by the presence of 16 anterior teeth in the
      prostom and filamented eggs in females. Rhabdochona acuminata was recorded for
      the first time in the north of Argentina.

PMID- 15986619
TI  - A new species of Cytauxzoon from Pallas' cats caught in Mongolia and comments on
      the systematics and taxonomy of piroplasmids.
AB  - DNA was extracted and the 18S ribosomal RNA gene was amplified and sequenced from
      the blood of 2 Pallas' cats (Otocolobus manul) infected with small
      intraerythrocytic piroplasms. Sequences of the parasite were found to be
      identical with that of a previously reported Cytauxzoon-like piroplasm from a
      Pallas' cat. Phylogenetic analyses of the parasite DNA sequences obtained from
      the 3 Pallas' cats to other piroplasms revealed a sister group relationship to C.
      felis. The mean corrected percent sequence divergence between the Pallas' cat
      parasite and C. felis was 1.490%, which is greater than that for most other
      piroplasms in which species status has been accepted. On the basis of the
      sequence variation, we propose to name the Pallas' cat parasite C. manul.
      Phylogenetic analyses of C. manul also revealed a close relationship with the
      Spanish Cytauxzoon-like isolate because they exhibited only 0.389% sequence
      divergence, yet these sequences exhibit a mean of 1.690% sequence divergence from
      the New World isolate of C. felis. Our phylogenetic analyses also revealed
      several taxonomic problems that have impeded the development of a classification
      that accurately reflects evolutionary history of piroplasms. As currently
      arranged, Babesia and Theileria are paraphyletic taxa and are in need of
      reorganization.

PMID- 15986620
TI  - New caligiform Copepod (Siphonostomatoida: Dissonidae) parasitic on Seriola
      hippos from western Australian waters, with new records and orphological
      variation for Dissonus nudiventris and Dissonus similis, and an updated key to
      the species of Dissonus.
AB  - Dissonus hoi n. sp. is described from female and male specimens collected from
      the nasal cavities of a Samson Fish (Seriola hippos Gunther) captured off
      Rottnest Island, Western Australia. Adult female D. hoi are distinguished from
      their congeners by possessing the following combination of characters: (1) a
      quadrangular genital complex, (2) ventral spines on the genital complex, (3) pair
      of postantennal processes, (4) a sternal furca, (5) 1-segmented abdomen, and (6)
      convoluted, uniseriate egg strings. New records and intraspecific morphological
      variation are also given for Dissonus nudiventris collected from Australia, and
      Dissonus similis collected from the tropical western Pacific. A key to the valid
      species of Dissonus is provided.

PMID- 15986621
TI  - Parhadjelia cairinae n. sp. (Nematoda: Habronematoidea: Habronematidae) in the
      Muscovy duck, Cairina moschata (Linnaeus, 1758) (Aves: Anseriformes: Anatidae),
      from the area de conservacion Guanacaste, Costa Rica.
AB  - A new species of Parahadjelia occurs in the muscovy duck, Cairina moschata
      (Linnaeus, 1758), from the Area de Conservacion Guanacaste, Costa Rica. The new
      species differs from Parhadjelia neglecta Lent and Freitas, 1939, in the body
      size, in the spicules shape and ratio of spicules, and in having 2 pairs of
      sessile papillae near the tail tip of the male. The characters exhibited by P.
      neglecta and the new species validate its generic status distinct from Hadjelia.

PMID- 15986622
TI  - Skrjabinura gnedina, 1933 (Nematoda: Seuratoidea: Seuratidae), in birds from the
      area de conservacion Guanacaste, Costa Rica with description of a new species.
AB  - Two species of Skrjabinura Gnedina, 1933, were collected in the intestines of
      birds from the Area de Conservacion Guanacaste (ACG), Costa Rica. Skrjabinura
      mesoamericana n. sp. inhabits Dendrocincla homochroa, Calocitta formosa,
      Dendrocolaptes certhia, Basileuterus rufifrons, and Chordeiles acutipennis. The
      new species differs from all species of the genus by having dissimilar spicules,
      the right having a distinctive thin and bent handle on the proximal end. The new
      species can be further distinguished from Skrjabinura pomatostomi and Skrjabinura
      brevicaudatum by having subequal versus equal spicules. Skrjabinura mesoamericana
      resembles S. brevicaudatum in the number and arrangement of male caudal papillae
      but differs in the vulva position and in having smaller eggs. The new species
      differs from S. potamostomi in having 6 versus 8 pairs of postcloacal papillae.
      Among those species having subequal spicules, the new species further differs
      from Skrjabinura spiralis in having 1 pair of paracloacal papillae and 6 pairs of
      postcloacal papillae, versus no paracloacal papillae and 4 pairs of postcloacal
      papillae, and in the vulva position. The new species is perhaps most similar to
      Skrjabinura vali, from which it further differs by having 3 pairs of precloacal,
      1 pair of paracloacal, and 6 pairs of postcloacal versus 2 pairs of precloacal, 2
      pairs of paracloacal, and 6 pairs of postcloacal papillae in the vulva position
      and in the shape of the eggs. Skrjabinura vali (Guerrero, 1971) Chabaud, 1978,
      originally described in Piaya cayana from Venezuela, occurs in the small
      intestine of P. cayana, as well as the new hosts, Crotophaga sulcirostris and
      Myiarchus tyrannulus, in the ACG, a new locality. Our specimens differ from the
      original description in the body length of the female, the numbers of postanal
      papillae of male tail, and the size of eggs.

PMID- 15986623
TI  - Recombinant NhSAG1 ELISA: a sensitive and specific assay for detecting antibodies
      against Neospora hughesi in equine serum.
AB  - Neospora hughesi is a recently identified cause of equine protozoal
      myeloencephalitis. However, the significance of this parasite is poorly
      understood. An enzyme-linked immunosorbent assay (ELISA) with a recombinant form
      of the N. hughesi 29-kDa surface antigen (rNhSAG1) was developed for
      serodiagnosis of equine N. hughesi infections. Parallel ELISA analysis showed
      that animals immunized or infected with N. hughesi exhibited greater antibody
      reactivity with rNhSAG1 than with the Neospora caninum homolog, rNcSAG1. The
      rNhSAG1 ELISA showed 94.4% sensitivity and 95.0% specificity when compared with
      N. hughesi western blot results for 1,006 samples. The N. hughesi seroprevalence
      was 3.4% for the 1,917 samples tested by ELISA, which is less than earlier
      reports. Importantly, western blot analysis of ELISA-positive sera revealed only
      18 true seropositive samples for an even lower seroprevalence of 0.9%. These
      results imply that Neospora spp. infections are uncommon in horses. The
      sensitivity and specificity exhibited by the rNhSAG1 ELISA suggest that it has a
      potential use for serodiagnosis of N. hughesi infection in equids. Furthermore,
      the high-throughput capability of the ELISA will allow for screening large sample
      sets, which should provide a better understanding of N. hughesi epidemiology.

PMID- 15986624
TI  - Evaluation of procedures to determine absolute density of Plasmodium vivax
      ookinetes.
AB  - The ookinete is the key determinant of infection within the mosquito vector, yet
      there are few population studies of ookinetes in nature. This investigation
      compared different techniques used to estimate ookinete densities in mosquitoes.
      Laboratory-reared Anopheles dirus mosquitoes were fed on gametocytemic blood
      drawn from 7 Plasmodium vivax patients at a malaria clinic in Mae Sot, Thailand.
      At 20-26 hr, bloodmeals were excised. Three techniques were evaluated, i.e.,
      hemacytometer counts under phase-contrast microscope, Giemsa staining of
      bloodmeal smears, and immunofluorescent staining with a monoclonal antibody
      specific against the 25-kDa antigen expressed on the surface of P. vivax zygotes
      and ookinetes. Additional mosquitoes were dissected at day 10 for oocysts. The
      hemacytometer method was the simplest and quickest method but lacked precision at
      low ookinete densities. Immunofluorescent staining was the most sensitive,
      accurate, and the only method that enabled unequivocal detection of zygotes.
      Bloodmeals contained a mixture of zygotes, retorts, and mature ookinetes,
      indicating that postzygotic development of P. vivax in A. dirus was asynchronous.
      The conversion efficiency of zygotes/ookinetes to oocysts varied among patients
      and was independent of zygote-ookinete density, suggesting that variations in
      host blood composition, e.g., antibodies, drugs, etc., may influence the success
      of zygote-ookinete development.

PMID- 15986625
TI  - Polymerase chain reaction detection of Cytauxzoon felis from field-collected
      ticks and sequence analysis of the small subunit and internal transcribed spacer
      1 region of the ribosomal RNA gene.
AB  - Cytauxzoon felis produces a disease in domestic cats in the Midwest (U.S.A.),
      which often leads to a fatal outcome. Although the clinical disease process is
      well described, there are still many unanswered questions about this organism.
      For example, it is unknown whether species of ticks other than Dermacentor
      variabilis can serve as vectors for transmission. With recent reports of
      surviving cats from limited geographic areas, another relevant question is the
      potential for genetically less virulent organism strains. This study evaluated
      352 individual or pooled tick samples (1,362 total ticks) for the presence of C.
      felis small subunit ribosomal RNA and internal transcribed spacer 1 (ITS-1)
      region genes using a polymerase chain reaction (PCR). These ticks were collected
      from dogs and cats in several Missouri counties, including 10 from cats diagnosed
      with cytauxzoonosis. Only 3 positive C. felis samples were identified in
      Amblyomma americanum nymphs, and there was very limited genetic variation noted
      in both genes. The small number of positive samples did not allow the study to
      determine which PCR analysis was more sensitive. This is the first known report
      of ITS-1 gene identification and sequencing for C. felis. It is also the first
      published investigation of genetic variation in C. felis.

PMID- 15986626
TI  - Observations on the Vietnam Palo Alto strain of Plasmodium vivax in two species
      of Aotus monkeys.
AB  - Thirty-three splenectomized Aotus lemurinus griseimembra monkeys with no previous
      experience with malaria were infected with the Vietnam Palo Alto strain of
      Plasmodium vivax. The median maximum parasite count was 280,000/microl. Nine
      splenectomized monkeys with previous infection with Plasmodium falciparum had
      median maximum parasite counts of 120,000/microl. Splenectomized Aotus nancymai
      monkeys supported infections at a lower level. Transmission via the bites of
      Anopheles dirus mosquitoes was obtained in a splenectomized A. lemurinus
      griseimembra, with a prepatent period of 31 days. It is estimated that between
      1.5 x 10(8) and 1.6 x 10(9) parasites can be removed from an infected animal for
      molecular or diagnostic antigenic studies.

PMID- 15986627
TI  - Molecular characterization of human pathogen Babesia EU1 in Ixodes ricinus ticks
      from Slovenia.
AB  - New cases of human babesiosis were recently reported in Europe. The etiological
      agent was identified as Babesia EU1, a zoonotic pathogen with previously
      unreported molecular characteristics. On the basis of a comparison of the
      complete babesial 18S rRNA gene, we have generated strong molecular evidence that
      Ixodes ricinus ticks from Slovenia are infected with EU1.

PMID- 15986628
TI  - Hesperoctenes fumarius (Hemiptera: Polycteenidae) infesting Molossus rufus
      (Chiroptera: molossidae) in southeastern Brazil.
AB  - We analyzed the prevalence, intensity, and medium density of parasitism of
      Hesperoctenes fumarius infesting Molossus rufus in natural (hollow trees) and
      anthropogenic roosts (attics) in southeastern Brazil. The prevalence and
      intensity of infestations were higher in the hollow trees than in the attic
      roosts. We also noted a relationship between the amount of space available within
      the roost and the infestation levels of H. fumarius. One advantage of roosting in
      larger, often man-made, refuges may be the reduction in ectoparasite
      infestations.

PMID- 15986629
TI  - Suppressed cytokine and immunoglobulin secretions by murine splenic lymphocytes
      infected in vitro with Toxoplasma gondii tachyzoites.
AB  - Mechanisms of host immunosuppression after infection with Toxoplasma gondii are
      unclear. This study was performed to observe cytokine and immunoglobulin
      secretions by murine splenic lymphocytes infected in vitro with live,
      nonreplicating (irradiated) RH tachyzoites on stimulation with concanavalin A
      (Con A) or lipopolysaccharide (LPS). For lymphocyte cultivation, 3 groups were
      prepared: coculture with live nonirradiated tachyzoites separated by a transwell
      (group T), live irradiated tachyzoites without a transwell (group R), and no
      tachyzoites (group C). Compared with group T, groups R and C, on stimulation with
      Con A, revealed significantly (P < 0.05) lower levels of interleukin-2 (IL-2) and
      IFN-gamma, but not IL-10. The levels of IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM
      were also significantly (P < 0.05) lower in groups R and C than in group T after
      stimulation with LPS. The results suggest that intracellular infection of murine
      splenic lymphocytes with T. gondii tachyzoites could impair their capacity to
      produce cytokine and immunoglobulin secretions.

PMID- 15986630
TI  - Prevalence of antibodies to Trypanosoma cruzi in raccoons (Procyon lotor) from an
      urban area of northern Virginia.
AB  - Raccoons (Procyon lotor) are reservoir hosts for Trypanosoma cruzi. A 3-yr-long
      serological survey was conducted to determine the prevalence of antibodies to
      this zoonotic parasite in raccoons collected from Fairfax County, Virginia, a
      suburban/urban area outside Washington, D.C. Serum samples from 464 raccoons were
      examined for T. cruzi antibodies at a 1:40 dilution with an indirect fluorescent
      antibody test (IFAT) and Brazil strain T. cruzi amastigotes and trypomastigotes
      as antigen. A positive IFAT test was found in 154 (33%) of the 464 samples. The
      yearly prevalence was 49 of 132 (37%) in 2000; 19 of 120 (16%) in 2001; and 86 of
      212 (41%) in 2002. Our study indicates that raccoons in this area of Virginia are
      frequently exposed to T. cruzi.

PMID- 15986631
TI  - Vertebrate host specificity of two avian malaria parasites of the subgenus
      Novyella: Plasmodium nucleophilum and Plasmodium vaughani.
AB  - The susceptibility of wild-caught European passeriform birds to naturally
      isolated malaria parasites, Plasmodium (Novyella) nucleophilum and Plasmodium
      (Novyella) vaughani, was studied by means of intramuscular subinoculation of
      infected citrated blood. Plasmodium nucleophilum of the great tit, Parus major,
      was transmitted to 3 great tits, but 3 blackcaps (Sylvia atricapilla) were not
      susceptible. Plasmodium vaughani of the robin, Erithacus rubecula, was
      transmitted to 1 robin and 1 blackcap, but 1 dunnock, Prunella modularis, was not
      susceptible. The prepatent period was between 8 and 10 days in all experimental
      infections. Maximum experimental parasitemia (3.4% of red cells) was detected in
      great tits infected with P. nucleophilum 23 days postexposure. A light (<0.01%)
      transient parasitemia of P. vaughani developed in the robin and blackcap. This
      study is in accord with former experimental observations on host specificity of
      P. nucleophilum and P. vaughani, which are characterized by a wide, but
      selective, range of avian hosts. Two new host-parasite associations were
      recorded.

PMID- 15986632
TI  - Trematodes in snails near raccoon latrines suggest a final host role for this
      mammal in California salt marshes.
AB  - Of the 18 trematode species that use the horn snail, Cerithidea californica, as a
      first intermediate host, 6 have the potential to use raccoons as a final host.
      The presence of raccoon latrines in Carpinteria Salt Marsh, California, allowed
      us to investigate associations between raccoons and trematodes in snails. Two
      trematode species, Probolocoryphe uca and Stictodora hancocki, occurred at higher
      prevalences in snails near raccoon latrines than in snails away from latrines,
      suggesting that raccoons may serve as final hosts for these species. Fecal
      remains indicated that raccoons fed on shore crabs, the second intermediate host
      for P. uca, and fish, the second intermediate host for S. hancocki. The increase
      in raccoon populations in the suburban areas surrounding west coast salt marshes
      could increase their importance as final hosts for trematodes in this system.

PMID- 15986633
TI  - Expression of P23 of Cryptosporidium parvum in Toxoplasma gondii and evaluation
      of its protective effects.
AB  - In this study, P23 of Cryptosporidium parvum sporozoites, an immunodominant
      surface protein, was stably expressed in Toxoplasma gondii (Tg/P23) and its
      protective effects were evaluated in a mouse model. The molecular weight and
      antigenic property of P23 expressed by Tg/P23 were similar to those of the native
      P23. Mice immunized with lysed Tg/P23 tachyzoites produced specific neutralizing
      antibodies against C. parvum. These findings indicate that the T. gondii vector
      may provide a new tool for the production of a recombinant vaccine against
      cryptosporidiosis in animals.

PMID- 15986634
TI  - Infection of Saimiri boliviensis monkeys with Plasmodium coatneyi.
AB  - Abundant, apparently normally developing, liver-stage parasites of Plasmodium
      coatneyi were demonstrated following injection of sporozoites dissected from the
      salivary glands of Anopheles dirus mosquitoes. Erythrocytic development was not
      demonstrated.

PMID- 15986635
TI  - [Gynecomastia (of the adult)].

PMID- 15986637
TI  - [Pancreatic carcinoma--symptoms and diagnostic procedure].
AB  - Pancreatic carcinoma is characterized by painful symptoms and an extraordinary
      unfavourable prognosis. To offer the patient a therapy adjusted to the individual
      situation the diagnostic work-up has to clear several questions. It is essential
      to have reliable proof of the diagnosis itself, as well as the stage of the
      disease. In addition, one should be able to locate the origin of complaints. The
      diagnostic power of the available invasive and non-invasive techniques increased
      in recent years. The quality of the diagnostic means depends to a great amount on
      the experience of the investigator. The most important goal of the diagnostic
      procedure is to identify metastatic or locally advanced disease without
      laparotomy. In this case palliative therapy canbe initiated immediately. When the
      findings are not conclusive, only diagnostic laparotomy can definitely show
      ifthere is a chance for curative resection.

PMID- 15986636
TI  - [Endoscopic treatment of chronic pancreatitis].
AB  - Progress in understanding the etiology and pathogenesis of pancreatitis has not
      yet opened significant new therapeutic options. Apart from dietetic and analgesic
      concepts, interventional endoscopy and pancreatic surgery are the mainstays of
      therapy. The often complex pathological anatomy requires the complete
      armamentarium of interventional endoscopy including endoscopic ultrasound.
      Stenoses, fistulae, pseudocysts and retroperitoneal necroses can be treated
      endoscopically. Failures of endoscopic treatment, relapses and inflammatory
      tumors of the pancreatic head as well as suspected malignancy should be operated.
      Endoscopic as well as surgical procedures are demanding and should be carried out
      by experienced teams with a sufficient case volume.

PMID- 15986638
TI  - [Chemotherapy of pancreatic carcinoma].
AB  - Patients with advanced pancreatic carcinoma benefit from chemotherapy with
      gemcitabine or 5-FU based regimens. Promising new combinations schedules with
      e.g. oxaliplatin, docetaxel, or erlotinib are under development. A survival
      benefit of adjuvant chemotherapy--after complete surgical resection of the
      primary tumor--has been demonstrated in some studies.

PMID- 15986639
TI  - [Pancreas carcinoma--surgical therapy].
AB  - The incidence of pancreatic cancer is increasing. The tumor growths extremely
      aggressive, long-term prognosis is dismal. Nevertheless, surgical therapy
      provides the only chance for cure and longterm survival. Achievement of an R0
      situation certainly is the primary surgical therapeutic goal. Reduction of
      surgical radicality in respect to the stomach and the pancreas itself obviously
      does not influence long-term survival of the patients. Thus, in the majority of
      patients the pylorus-preserving resection of the head of the pancreas seems to be
      the best operative strategy for resection of a carcinoma in the head of the
      pancreas. Concerning lymphadenectomy and resection of the portal or superior
      mesenteric vein surgical radicality is increasing during the last years.
      Perioperative mortality after resection of the head of the pancreas could be
      reduced in high volume centers below 5%. This is true even if parts of the portal
      or superior mesenteric vein are resected in addition. There are for the first
      time reports of patients who have survived longer than 5 years after resection of
      a pancreatic carcinoma. Further improvement of long-term survival, however, will
      not be achieved by increasing surgical aggressiveness but only by the use of new
      multimodal therapeutic protocols.

PMID- 15986640
TI  - [Chronic pancreatis and pancreatic carcinoma in the elderly].
AB  - Chronic pancreatitis is mostly caused by heavy alcohol consumption and is
      characterized by the onset of symptoms in the fourth and fifth decade. Beginning
      in patients older than 65 years of age is rare. Leading symptom is recurrent or
      persisting abdominal pain which is missed only in approximately 5% of the cases.
      Chronic pancreatitis is classified as idiopathic if there is no anamnesis of
      alcohol abuse or some rare specific causes. The Idiopathic Chronic Senile
      Pancreatitis (ICSP) is a subset of the non-alcoholic pancreatitis and is
      characterized by advanced age at the time of first manifestation. Although life
      expectancy especially in chronic alcoholic pancreatitis is reduced, there are
      many patients who reach older age. The natural history in all forms of chronic
      pancreatitis shows a decrease in pain and the manifestation of exocrine and
      endocrine insufficiency as late complications. Especially in the elderly loss of
      weight may occur with steatorrhea and pancreatic diabetes mellitus as the
      dominating clinical problem of chronic pancreatitis. If pain persists treatment
      is symptomatically with analgesics. The possibility of causal surgery or the
      indication for endoscopic treatment of painful chronic pancreatitis should be
      proven in every single case. Standard pancreatin treatment consisting of large
      amounts of enzymes will abolish maldigestion. Pancreatic diabetes requires often
      insulin, there is a tendency to hypoglycaemia. In contrast to chronic
      pancreatitis cancer of the pancreas is a typical and frequent disease of the
      elderly. The prognosis is bad and one year life expectancy is just about 11%. One
      of the reasons is, that the diagnosis is found lately because early symptoms are
      missing. Specific symptoms like pain, weight loss or jaundice occur lately. In
      suspicion of pancreatic cancer a lot of methods of morphological diagnostic are
      available such as CT, MRCP, ultrasound, ERCP and PET, in addition the specific
      tumor markers CA 19-9 and CEA. After diagnostic is completed, curative resection
      is possible in only a low percentage of all cases. Old age is no contraindication
      for surgery, prognosis and the risk of surgery don't differ to other age groups.
      In most cases palliative therapy is the only possible option because of an
      advanced tumor stage. Sufficient pain therapy, endoscopic stenting in case of
      obstructive jaundice or gastroenterostomy in case of duodenal are useful
      interventions.

PMID- 15986641
TI  - Fabrication of gradient hydrogels using a microfluidics/photopolymerization
      process.
AB  - A method of fabricating photo-cross-linked hydrogels with gradients of
      immobilized molecules and crosslinking densities is introduced. Two
      macromer/initiator solutions are injected into a unique poly(dimethylsiloxane)
      channel system that produces a prepolymer gradient that is subsequently
      polymerized into a water-swollen hydrogel with ultraviolet light exposure. The
      gradient is controlled by the injection flow rate (optimized to 0.3 microL/min
      per inlet to produce a linear gradient). The technique is investigated both
      through fabrication of adhesive ligand gradients that modulate spatial
      distribution of attached endothelial cells and gradients of cross-linking
      densities that led to unique hydrogel architectures and spatially dependent
      swelling.

PMID- 15986642
TI  - Graphitic mesostructured carbon prepared from aromatic precursors.
AB  - Mesostructured carbons with graphitic framework walls are conveniently prepared
      at ambient pressures through the replication of a mesostructured silica template
      using an aromatic hydrocarbon as the carbon precursor and a catalyst.

PMID- 15986643
TI  - Membrane fusion of giant unilamellar vesicles of neutral phospholipid membranes
      induced by La3+.
AB  - Membrane fusions of vesicles of biomembranes play various important roles in
      cells, but their mechanisms are unclear and controversial. In the present study,
      we found that 30 microM to 1 mM La3+ induced membrane fusion of two giant
      unilamellar vesicles (GUVs) composed of a mixture of dioleoylphosphatidylcholine
      (DOPC) and dipalmitoleoylphosphatidylethanolamine (DPOPE). We succeeded in
      observing a process of this membrane fusion in detail. First, two GUVs became
      strongly associated, with a partition membrane between them composed of two
      bilayers, one from each GUV. Then, the partition membrane was suddenly broken at
      one site on its edge. The area of this breakage site gradually spread, until it
      was completely separated from the GUV to complete the membrane fusion. Here, we
      propose a new model (i.e., the partition breakage model) for the mechanism of
      La3+ -induced membrane fusion of GUVs.

PMID- 15986644
TI  - Complex formation between cationically modified gold nanoparticles and DNA: an
      atomic force microscopic study.
AB  - Atomic force microscopy has been used for direct visualization of the wrapping of
      DNA around 30-nm-sized functionalized gold nanoparticles for the first time. The
      morphology of the complexes seems to be dictated by the relative concentration of
      the nanoparticles and DNA. A higher concentration of the former leads to the
      formation of a network of nanoparticles assembled on DNA. This assembly pattern
      seems to be significantly different from the manner in which cationically
      modified gold nanoparticles of smaller size (< 5 nm) arrange linearly on DNA, as
      shown in the literature. A DNA-gold nanoparticle can be developed as a model
      system for in vitro studies on the mechanism of DNA condensation and also for
      developing novel methods of nanoparticle self-assembly on the DNA template.

PMID- 15986645
TI  - Mobility and in situ aggregation of charged microparticles at oil-water
      interfaces.
AB  - Particle mobility, aggregate structure, and the mechanism of aggregate growth at
      the two-dimensional level have been of long-standing interest. Here, we use solid
      stabilized emulsions as a model system to investigate the mobility of charged
      microparticles at poly(dimethylsiloxane) (oil)-water interfaces using confocal
      laser scanning microscopy. Remarkably, the rate of diffusion of the charged
      colloidal-sized polystyrene particles at the oil-water interface is only
      moderately slower than that in the bulk water phase. The ambient diffusion
      constant of solid particles is significantly reduced from 1.1 x 10(-9) cm2/s to
      2.1 x 10(-11) cm2/s when the viscosity of the oil phase increases from 5 cSt to
      350 cSt. In addition, we successfully observe the in situ structural formation of
      solid particles at the oil-water interface.

PMID- 15986646
TI  - Controlled nucleation and growth of thin hydroxyapatite layers on titanium
      implants by using induction heating technique.
AB  - This paper reports the results obtained by the development of a new wet method of
      hydroxyapatite (HA) thin layer deposition. The method is based on the localized
      precipitation of HA on metallic substrates activated by induction heating. The
      technique developed has been shown to allow for the complete coating of
      substrates with micrometric thin films of HA within a low processing time. The
      method has been successfully applied to coat Ti plaques and Ti-6A1-4V cylinders.

PMID- 15986647
TI  - Apparent equilibration time required for surfactant-oil-water systems to emulsify
      into the morphology imposed by the formulation. Part 2: Effect of sec-butanol
      concentration and initial location.
AB  - Winsor type I equilibrated surfactant-oil-water (SOW) systems produce o/w
      emulsions upon stirring. However, if the surfactant is initially dissolved in the
      oil phase, the attained type after inmediate emulsification is usually w/o. If
      the SOW system is partially equilibrated, it could result in a normal o/w
      emulsion, as if it were fully equilibrated. The minimum contact time for that to
      happen, the so-called apparent equilibration time tAPE, was previously shown
      (Langmuir 2002, 18, 607) to strongly depend on formulation, surfactant molecular
      weight, and oil viscosity. The present report shows that it depends on alcohol
      concentration and location in the unequilibrated system.

PMID- 15986648
TI  - Generation of amino-terminated surfaces by chemical lithography using atomic
      force microscopy.
AB  - Self-assembled monolayers (SAMs) covered with nitroso end groups were reduced
      using an atomic force microscope. As the bias voltage become more negative
      (beyond -4 V), the surface potential of the scanned area become closer to that of
      the amino-terminated SAM. Following this chemical change, however, no change in
      topographic features was detected, implying retained stability of the underlying
      SAM layer. We then released carboxylate-modified polystyrene (PS) spheres into a
      pH 4 solution containing the sample. Subsequent imaging with atomic force
      microscopy (AFM) revealed that these PS spheres were only selectively immobilized
      on the regions that were originally scanned at -6 V to form amino termination. In
      summary, using AFM set to a specific voltage, we were able to selectively
      generate micropatterned regions of the SAM with amino termination.

PMID- 15986649
TI  - Phase diagrams of nonionic foam films: new interpretation of disjoining pressure
      vs thickness curves.
AB  - Recently we constructed phase diagrams for thin foam films stabilized by a
      nonionic surfactant. The idea was born by synopsis of various disjoining pressure
      (pi) versus thickness (h) curves of foam films resembling p-Vm isotherms of real
      gases. The new concept of interpreting the pi-h curves of foam films in terms of
      phase diagrams allows us to describe experimental observations much more
      precisely. Three logical consequences will be discussed here to illustrate the
      strength of this approach. First, the observation is explained that common black
      films (CBF) rupture or form a Newton black film (NBF) within a certain pressure
      range rather than at a defined pressure. Both observations can be rationalized by
      invoking a nucleation process of holes or of the thinner NBF, respectively, in
      close analogy to the vapor to liquid condensation. Second, the question whether
      the CBF to NBF transition is discrete or continuous is answered by analyzing
      under which conditions the supercritical state of a foam film can be reached.
      Third, the evidence of corresponding states is discussed.

PMID- 15986650
TI  - Synthesis of gold nanoparticles from an organometallic compound in supercritical
      carbon dioxide.
AB  - This article presents the synthesis of gold nanoparticles in a single-phase
      supercritical fluid carbon dioxide solvent. The gold nanoparticles were formed by
      the reduction of triphenylphosphine gold(I) perfluorooctanoate with
      dimethylamineborane. Transmission electron microscopy, X-ray photoelectron
      spectroscopy, and UV-vis spectroscopy reveal the formation of gold nanoparticles
      of 1 nm in diameter. A high dispersion stability of the gold nanoparticles in
      supercritical carbon dioxide can be obtained by binding both triphenylphosphine
      and fluorocarbon ligands on the surface of the gold nanoparticles.

PMID- 15986651
TI  - Novel one-step route for synthesizing CdS/polystyrene nanocomposite hollow
      spheres.
AB  - CdS/polystyrene nanocomposite hollow spheres with diameters between 240 and 500
      nm were synthesized under ambient conditions by a novel microemulsion method in
      which the polymerization of styrene and the formation of CdS nanoparticles were
      initiated by gamma-irradiation. The product was characterized by transmission
      electron microscopy (TEM), field-emission scanning electron microscopy (FESEM), X
      ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and
      thermogravimetric analysis (TGA), which show the walls of the hollow spheres are
      porous and composed of polystyrene containing homogeneously dispersed CdS
      nanoparticles. The quantum-confined effect of the CdS/polystyrene nanocomposite
      hollow spheres is confirmed by the ultraviolet-visible (UV-vis) and
      photoluminescent (PL) spectra. We propose that the walls of these nanocomposite
      hollow spheres originate from the simultaneous synthesis of polystyrene and CdS
      nanoparticles at the interface of microemulsion droplets. This novel method is
      expected to produce various inorganic/polymer nanocomposite hollow spheres with
      potential applications in the fields of materials science and biotechnology.

PMID- 15986652
TI  - Temperature driven morphological changes of chemically precipitated
      hydroxyapatite nanoparticles.
AB  - Hydroxyapatite (HA) is synthesized by a wet chemical route using calcium
      hydroxide and ortho-phosphoric acid at various temperatures (40, 80, and 100
      degrees C). X-ray diffraction of the precipitate particles revealed HA as the
      predominant phase (>99%) with a small amount of beta-tricalcium phosphate.
      Fourier transform infrared spectroscopy indicated the presence of carbonate
      substitution, which decreased with increasing temperature. Transmission electron
      microscopy observations revealed needle-shaped particles with a high aspect ratio
      at 40 degrees C, which changed to spheroidal when the precipitation temperature
      was increased to 100 degrees C. The changes in the morphology with temperature
      were analyzed taking into account the driving force for the HA precipitation and
      the supersaturation level of Ca2+ and PO4(3-) ions with respect to HA. The
      analysis indicated that the supersaturation level of the reactants, especially
      the concentration of Ca2+ ions, played a predominant role on the precipitate
      morphology for this classical acid-base reaction.

PMID- 15986653
TI  - Oxidation of thioanisole by peroxomolybdate in assemblies of cetylpyridinium
      chloride and methyltri-n-octylammonium chloride.
AB  - Methyltri-n-octylammonium chloride (Aliquat 336) is sparingly soluble in water
      but is readily soluble with a 2-fold excess of micellized cetylpyridinium
      chloride (CPyCl), and the mixtures show breaks in plots of surface tension or
      electrolytic conductance against concentration indicative of a critical micelle
      concentration slightly lower than that of CPyCl. Micellization markedly increases
      35Cl and 14N NMR line widths of CPyCl, but addition of NaCl reduces the 35Cl line
      width and addition of Aliquat increases it. Mixing Aliquat and CPyCl has little
      effect on their 14N line widths. Ion pairing in alcohol mixtures also increases
      35Cl line widths. In water these mixed assemblies behave similarly to micelles of
      CPyCl as regards effects on rates and equilibria of interconversion of tri- and
      tetraperoxomolybdate ions, and oxidation of thioanisole by the latter, although
      it is slightly slower than in micelles of CPyCl. Despite differences in the
      hydrophobic regions, and relationships between amphiphilic structures and
      morphologies of association colloids, assemblies of CPyCl and Aliquat behave very
      much like CPyCl micelles in their physical properties and effects upon
      reactivity. Geometrical optimization indicates that Aliquat can adopt
      conformations that allow intercalation with CPyCl micelles.

PMID- 15986654
TI  - Emission behavior of 1-methylaminopyrene in aqueous solution of anionic
      surfactants.
AB  - A new fluorescent probe, methylamino derivative of pyrene, has been considered to
      characterize the concentration dependent emission behavior of an aqueous solution
      of anionic surfactants, viz., SDS, DSS, and SDBS. It was found that the emission
      of the probe is uniquely sensitive to the changes in surfactant (anionic)
      concentration due to the functional group effect of the probe over the parent
      moiety, pyrene. Here, 1-methylaminopyrene (MAP) showed significant quenching of
      emission well below the critical micellar concentration (cmc) of the surfactant.
      Excimer emission of the probe due to the formation of premicellar aggregates of
      the surfactant solutions at a concentration close to but below the cmc and again
      an enhanced emission of the probe above the cmc were observed as a consequence of
      definite MAP-surfactant interactions. These observations assisted the possible
      quantification ofsurfactant concentrations and their chain length dependent
      premicellar aggregate formations. Significant monomer emission in relation to
      probe distribution in micelle was analytically authenticated. Dynamic light
      scattering (DLS) studies revealed the incorporation of the probe molecules in the
      micellar core. The fluorophore emission showed nonlinear behavior when the
      surfactant concentration was far above the cmc. Abrupt changes in the emission
      characteristics in relation to the micellar concentration led to the
      determination of the cmc of the surfactants.

PMID- 15986655
TI  - Complexation of anionic polyelectrolytes with cationic liposomes: evidence of
      reentrant condensation and lipoplex formation.
AB  - We have studied the complexation process taking place in cationic liposomes in
      the presence of anionic polyelectrolytes, in the polyion concentration range from
      the dilute to the concentrated regime, by combining dynamic light scattering and
      transmission electron microscopy techniques. We employed as the cationic lipid a
      two-chained amphiphile (Dioleoyltrimethylammoniumpropane) and sodium polyacrylate
      salt as the flexible anionic polyelectrolyte. The results evidence a variety of
      different structures, mainly depending on the liposome-polyion charge ratio,
      whose peculiar dynamical and structural features are briefly described. In
      particular, three different polyion concentration regions are found, within which
      a monomodal or bimodal distribution of aggregates, with a well-defined time
      evolution, is present. At low polyion content, close to the isoelectric point,
      large aggregates are formed, deriving from the collapse of the liposomal bilayers
      into extended charged surfaces, where adsorbed polyions form a two-dimensional
      strongly correlated array and organize into a two-dimensional Wigner liquid. At
      high polyion content, above a critical concentration, the size distributions of
      the complexes are clearly bimodal and a large-component aggregate, continuously
      increasing with time, coexists with a population of smaller-size aggregates. At
      an intermediate polyion concentration, spherical, small-size vesicular structures
      are reformed, connected in a network by polymer chains. A brief discussion tries
      to summarize our results into a consistent picture.

PMID- 15986656
TI  - Structure of polymer-stabilized magnetic fluids: small-angle neutron scattering
      and mean-field lattice modeling.
AB  - Small-angle neutron scattering and mean-field lattice modeling were used to
      characterize a class of water-based magnetic fluids tailored specifically to
      extract soluble organic compounds from water. The fluids consist of a suspension
      of approximately 7 nm magnetite (Fe3O4) nanoparticles coated with a bifunctional
      polymer layer comprised of an outer hydrophilic poly(ethylene oxide) (PEO) region
      for colloidal stability and an inner hydrophobic poly(propylene oxide) (PPO)
      region for solubilization of organic compounds. The inner region of the polymer
      shell is increasingly depleted of water as the fraction of PPO side chains
      increases. The incorporation of PPO side chains also leads to a small increase in
      interparticle attraction. The lattice model predicted a shell structure similar
      to that of a PEO-PPO-PEO triblock copolymer (Pluronic) micelle, with equivalent
      levels of hydration but with more PEO present in the PPO-rich regions, as the
      side chains grafted to the surface are less able to segregate than when in free
      micellar systems.

PMID- 15986657
TI  - Rheology and dynamics of micellar cubic phases and related emulsions.
AB  - The rheological behavior of micellar cubic phases in C12EO25 systems and related
      emulsions has been investigated. In the aqueous C12EO25 binary system, the
      transition from the cubic phase to the micellar solution is associated with a
      sudden drop in viscosity and with a small enthalpy of transition. The elastic
      modulus and viscosity of the cubic phases show a maximum with concentration but
      remain very high within the range of existence of the cubic phase. Several
      relaxation processes seem to be present in binary cubic phases, and some of them
      occur in a time scale that can be followed by both rheology and dynamic light
      scattering measurements. Upon addition of a small amount of oil (decane), the
      rheological behavior changes remarkably. As the oil fraction increases, the
      relaxation times also increase and, finally, highly concentrated, gel-like
      emulsions are obtained. Contrary to conventional concentrated emulsions, the
      viscosity of cubic-phase-based emulsions is decreased by increasing the fraction
      of the dispersed phase. The non-Maxwellian rheological behavior at low oil
      fractions is described according to the model of slipping crystalline planes,
      modified by using a distribution of bulk relaxation times, and good fitting to
      the experimental data is obtained.

PMID- 15986658
TI  - Biocompatible lipidic formulations: phase behavior and microstructure.
AB  - Biocompatible systems formulated for use in the food, cosmetic, and
      pharmaceutical fields are characterized. Ternary phase diagrams of mixtures of
      natural lipids (glycerol trioleate, glycerol monooleate, diglycerol monooleate,
      and lecithin) and water were investigated by means of optical microscopy in
      polarized light and by multinuclear NMR spectroscopy. All systems showed a
      microemulsion region at high oil content and a large area of coexistence of two
      liquid crystalline (hexagonal and lamellar) phases. 1H and 13C NMR self-diffusion
      measurements were used to characterize microstructural features of the
      microemulsions. On water dilution, the two-phase liquid crystalline region
      transforms into a creamy emulsion area where the droplets of water are stabilized
      by both the lamellar and the hexagonal phases, as indicated by 2H NMR
      measurements. Due to the very effective dispersing action of the two liquid
      crystalline phases, these emulsions show a high stability toward phase
      separation.

PMID- 15986659
TI  - Preparation of submicrometer-sized monodispersed thermoresponsive core-shell
      hydrogel microspheres.
AB  - We have successfully prepared monodispersed thermoresponsive core-shell hydrogel
      microspheres with a mean diameter of 200-400 nm with poly(N-isopropylacrylamide
      co-styrene) [P(NIPAM-co-St)] cores and poly(N-isopropylacrylamide) (PNIPAM)
      shells. The submicrometer-sized monodispersed P(NIPAM-co-St) core seeds were
      prepared by using a surfactant-free emulsion polymerization method, and the
      PNIPAM shell layers were fabricated onto the core seeds by using a seed
      polymerization method. The particle size, morphology and monodispersity, and
      thermoresponsive characteristics of the prepared microspheres were experimentally
      studied. In the preparation of P(NIPAM-co-St) seeds, with increasing the
      initiator dosage, the mean diameters and the dispersal coefficients were almost
      at the same levels at first; however, when the initiator dosage increased further
      to a critical amount, the mean diameters decreased drastically and the
      monodispersity became worse significantly. With increasing the stirring rate, the
      particle diameter decreased, and when the stirring rate was larger than 600 rpm,
      the monodispersity became worse obviously. With increasing the phase ratio, the
      mean diameter became larger simply, and the monodispersity became worse first and
      then became better again. With increasing the reaction time, the particle sizes
      nearly did not change, while the monodispersity gradually became better slightly.
      For the core-shell microspheres, with increasing the NIPAM dosage in the
      preparation of the PNIPAM shell layers, the mean diameters became larger simply,
      the monodispersity became better, and the thermoresponsive swelling ratio of the
      hydrodynamic diameters increased.

PMID- 15986660
TI  - Reversible phase transitions in emulsified nanostructured lipid systems.
AB  - Aqueous submicron-sized dispersions of the binary monolinolein/water system,
      which are stabilized by means of a polymer, internally possess a distinct
      nanostructure. Taking this as our starting point, we were able to demonstrate for
      the first time that the internal structure of the dispersed particles can be
      tuned by temperature in a reversible way. Upon increasing the temperature, the
      internal structure undergoes a transition from cubic via hexagonal to fluid
      isotropic, the so-called L2 phase, and vice versa. Intriguingly, in addition to
      the structural changes in topology, the particles expel (take up) water to (from)
      the aqueous continuous phase when increasing (decreasing) the temperature in a
      reversible way. At each temperature, the internal structure of the dispersed
      particles corresponds very well to the structure observed in nondispersed binary
      monolinolein with excess water. This agreement is independent of any thermal
      history (including phase transitions), which proves that the structures in the
      dispersed particles actually are in thermodynamic equilibrium with the
      surrounding water phase.

PMID- 15986661
TI  - Nanoparticle-mediated epitaxial assembly of colloidal crystals on patterned
      substrates.
AB  - We have studied the assembly of 3-D colloidal crystals from binary mixtures of
      colloidal microspheres and highly charged nanoparticles on flat and epitaxially
      patterned substrates created by focused ion beam milling. The microspheres were
      settled onto these substrates from dilute binary mixtures. Laser scanning
      confocal microscopy was used to directly observe microsphere structural evolution
      during sedimentation, nanoparticle gelation, and subsequent drying. After
      microsphere settling, the nanoparticle solution surrounding the colloidal crystal
      was gelled in situ by introducing ammonia vapor, which increased the pH and
      enabled drying with minimal microsphere rearrangement. By infilling the dried
      colloidal crystals with an index-matched fluorescent dye solution, we generated
      full 3-D reconstructions of their structure including defects as a function of
      initial suspension composition and pitch of the patterned features. Through
      proper control over these important parameters, 3-D colloidal crystals were
      created with low defect densities suitable for use as templates for photonic
      crystals and photonic band gap materials.

PMID- 15986662
TI  - Nanosized gismondine grown in colloidal precursor solutions.
AB  - A colloidal molecular sieve with GIS-type structure was prepared from aged
      aluminosilicate precursor solutions containing tetramethylammonium (TMA)
      hydroxide under hydrothermal treatment at 100 degrees C. The nucleation and the
      development of the GIS zeolite structure were studied by dynamic light
      scattering, scanning electron microscopy, X-ray diffraction, Raman and infrared
      spectroscopies, and liquid-state NMR spectroscopy. It is shown that the aging at
      room temperature leads to the formation of subcolloidal particles that
      incorporate TMA cations and form larger aggregates. After an extended heating of
      13 days, a complete transformation from amorphous precursor material to
      crystalline GIS-type colloidal particles is observed. The mean hydrodynamic
      radius of the crystalline GIS particles is in the range of 30-50 nm. The specific
      template-framework interactions influence the spectral features of the TMA
      cations incorporated in the zeolite structure, thus making possible the use of
      the corresponding Raman spectra and 13C NMR data for the examination of the
      crystallinity of GIS-type colloidal particles stabilized in water.

PMID- 15986663
TI  - Adsorption of butane isomers and SF6 on Kureha activated carbon: 1. Equilibrium.
AB  - Adsorption equilibria of butane isomers and SF6 on Kureha activated carbon were
      investigated using the volumetric method and the tapered element oscillating
      microbalance (TEOM) technique. The isotherm data of the butane isomers measured
      by the TEOM technique are in good agreement with those determined by the
      volumetric method. Single-component adsorption isotherms are reported at
      temperatures in the range from 298 to 393 K and at pressures up to 120 kPa. SF6
      molecules are mainly adsorbed in the larger micropores, resulting in a lower
      adsorption capacity. The amount adsorbed for n-butane is slightly higher than
      that for isobutane in the whole range investigated. This is attributed to the
      fact that the linear n-butane molecule can adsorb in the smaller micropores. The
      T6th model appropriately describes the equilibrium data of the butane isomers,
      while the isotherm data of SF6 can be fitted by the Langmuir model. The isosteric
      heats associated with adsorption for these three adsorptives show different
      loading dependences. The present study indicates that the activated carbon can be
      well characterized by the probe molecules having different molecular sizes.

PMID- 15986664
TI  - Interfacial effects on moisture absorption in thin polymer films.
AB  - Moisture absorption in model photoresist films of poly(4-hydroxystryene) (PHOSt)
      and poly(tert-butoxycarboxystyrene) (PBOCSt) supported on silicon wafers was
      measured by X-ray and neutron reflectivity. The overall thickness change in the
      films upon moisture exposure was found to be dependent upon the initial film
      thickness. As the film becomes thinner, the swelling is enhanced. The enhanced
      swelling in the thin films is due to the attractive nature of the hydrophilic
      substrate, leading to an accumulation of water at the silicon/polymer interface
      and subsequently a gradient in concentration from the enhancement at the
      interface to the bulk concentration. As films become thinner, this interfacial
      excess dominates the swelling response of the film. This accumulation was
      confirmed experimentally using neutron reflectivity. The water rich layer extends
      25 +/- 10 A into the film with a maximum water concentration of approximately 30
      vol %. The excess layer was found to be polymer independent despite the order of
      magnitude difference in the water solubility in the bulk of the film. To test if
      the source of the thickness dependent behavior was the enhanced swelling at the
      interface, a simple, zero adjustable parameter model consisting of a fixed water
      rich layer at the interface and bulk swelling through the remainder of the film
      was developed and found to reasonably correspond to the measured thickness
      dependent swelling.

PMID- 15986665
TI  - New pi-complexation adsorbents for propane-propylene separation.
AB  - New adsorbents were prepared and tested for the separation of propane-propylene
      mixtures by adsorption. The ordered mesoporous material SBA-15 was used as the
      starting material for silver-ion deposition for pi-complexation with propylene.
      Two different loadings of silver were evaluated. Adsorption equilibrium and
      kinetic measurements of propane and propylene in the matrix (pure SBA-15) and the
      silver-modified adsorbents were performed at 323, 343, and 373 K. In this
      temperature range, the selectivity of propylene in one of the materials (Ag/SBA
      15 = 0.5) is in the range 13-22 because the amount of propane adsorbed is very
      small, 0.095 mmol/g of propane versus 1.12 mmol/g of propylene at 100 kPa and 343
      K. The diffusivity of both hydrocarbons is not seriously affected by the
      introduction of silver into the mesoporous structure.

PMID- 15986666
TI  - Particle adhesion force distributions on rough surfaces.
AB  - The effect of roughness on adhesion force distribution was studied in the gas
      phase. Spherical gold particles with diameters between 5 and 20 microm were
      generated in a flame process and glued onto atomic force microscope (AFM)
      cantilevers directly after. Nanostructured substrates with defined roughness were
      produced by a dip-coating process. The geometry of the adhering partners was
      determined by AFM imaging, and the adhesion force was measured with the AFM.
      Depending on the roughness of the particles and the substrates, three types of
      distribution functions can be identified; two of them can be explained with a
      simple model. The obtained adhesion force distributions not only agree with those
      experimentally recorded in previous studies of commercially important powders
      (e.g., alumina, toner, and gold on different substrates) but also agree with
      distributions reported in the literature.

PMID- 15986667
TI  - Aggregation states and surface wettability in films of poly(styrene-block-2
      perfluorooctyl ethyl acrylate) diblock copolymers synthesized by atom transfer
      radical polymerization.
AB  - Well-defined poly(styrene-block-2-perfluorooctyl ethyl acrylate) [P(St-b-PFA)]
      copolymers with various chemical compositions were synthesized by atom transfer
      radical polymerization. Films of P(St-b-PFA) were structurally characterized,
      from bulk to surface, on the basis of transmittance electron microscopic
      observation and small-angle X-ray scattering, X-ray photoelectron spectroscopic,
      and contact angle measurements. For a comparison, poly(styrene-random-2
      perfluorooctyl ethyl acrylate) [P(St-ran-PFA)] copolymers were also synthesized
      by conventional free radical polymerization. While P(St-b-PFA) with the 2
      perfluorooctyl ethyl acrylate (PFA) content higher than 18.7 mol % formed a
      typical phase-separated cylinder structure, P(St-b-PFA) with a lower PFA content
      and P(St-ran-PFA) were in a miscible state. Since the perfluoroalkyl groups
      possess extremely low surface energy, they were preferentially segregated at the
      film surface, resulting in the formation of the PFA surface layer. This was the
      case for all P(St-b-PFA) films examined, although the aggregation state at the
      surface was strongly dependent on the PFA content. In the case of the P(St-b-PFA)
      with the PFA content higher than 18.7 mol %, both advancing and receding contact
      angles for water were 120 degrees and even larger with almost no hysteresis. In
      addition, extremely excellent oil-repellent surface properties such as advancing
      and receding contact angles for dodecane of 76 degrees and 75 degrees were also
      observed. However, these intriguing liquid-repellent properties were not observed
      for the films of miscible P(St-b-PFA) and P(St-ran-PFA). Therefore, it can be
      concluded that the internal structure beneath the surface as well as the surface
      itself should be deeply considered to design excellent and stable liquid
      repellent materials.

PMID- 15986668
TI  - Optical and spectroscopic characteristics of oleate adsorption as revealed by
      FTIR analysis.
AB  - Fourier transform infrared transmission (FTIR/TS), external reflection
      (FTIR/ERS), and internal reflection (FTIR/IRS) spectroscopies are three important
      sampling techniques for the study of adsorbed surfactants. The optical and
      spectral characteristics of a three-phase system were calculated using
      theoretical simulation and discussed based on experimental results for oleate
      adsorption at the air/water interface and at the water/fluorite interface. It is
      shown that a thorough understanding of the optical properties and spectral
      characteristics from FTIR analysis helps to improve the experimental design and
      explanation of experimental results and is important to properly quantify
      surfactant interfacial adsorption phenomena.

PMID- 15986669
TI  - Fluidity of water confined down to subnanometer films.
AB  - A surface force balance with extremely high sensitivity and resolution for
      measuring shear forces across thin films has been used to investigate directly
      the dynamic properties of salt-free water (so-called conductivity water) in a gap
      between two atomically smooth solid surfaces. Our results reveal that no shear
      stress can be sustained by water (within our resolution and shear rates) down to
      films of thickness D = D0 = 0.0 +/- 0.3 nm. At short range (D < 3.5 +/- 1 nm), an
      attractive van der Waals (vdW) force between the surfaces causes a jump into a
      flat adhesive contact at D0, at which the surfaces rigidly couple. Analysis of
      the jump behavior reveals that the viscosity of water remains within a factor of
      3 or so of its bulk value down to D0. This contrasts sharply with the case of
      confined nonassociating liquids, whose effective viscosity increases by many
      orders of magnitude at film thicknesses lower than about five to eight
      monolayers. We attribute this to the fundamentally different mechanisms of
      solidification of organic liquids and of water. In the former case, the density
      increase induced in the films by the confinement promotes solidification, while,
      in the case of water, such densification (due to vdW attraction between the
      liquid molecules and the confining walls), in agreement with bulk behavior,
      suppresses the tendency of the water to solidify.

PMID- 15986670
TI  - Self-assembled monolayers of alpha,omega-diphosphonic acids on Ti enable complete
      or spatially controlled surface derivatization.
AB  - Alpha,omega-diphosphonic acids self-assemble on the native oxide surfaces of Ti
      or Ti-6Al-4V. Heating gives strongly bonded phosphonate monolayers. Infrared and
      X-ray spectroscopic and water contact angle data show that the films are bonded
      to the surface by one phosphonate unit; the other remains a phosphonic acid.
      Surface loadings were measured by quartz crystal microbalance procedures.
      Mechanical shear strengths for the films were also measured; these do not
      correlate simply with surface loadings. Films formed from 1,12
      diphosphonododecane were treated with zirconium tetra(tert-butoxide) to give
      surface Zr complex species; derivatives of these surface complexes are stable to
      hydrolysis under physiological conditions and are mechanically strong. The
      complexation reaction can be accomplished over the entire surface; alternatively,
      dropwise application of the alkoxide to the surface enables spatial control of
      deposition. The cell attractive peptide derivative RGDC can be bound to these
      surface Zr alkoxide complexes through (maleimido)-alkylcarboxylate intermediates.
      Surfaces modified with RGDC were shown to be effective for osteoblast binding and
      proliferation.

PMID- 15986671
TI  - Formation of Langmuir layers and surface modification using new upper-rim fully
      tethered bipyridinyl or bithiazolyl cyclodextrins and their fluorescent metal
      complexes.
AB  - Seven new amphiphilic cyclodextrins bearing bipyridyl or bithiazolyl moieties at
      the narrow rim and free hydroxyl or methoxyl groups at the wide rim of the
      cyclooctaamylose crown were synthesized using a one step "phosphine imide"
      approach. These ligands form metal complexes that have fluorescence properties
      with potentials for optical applications. Here, the cyclodextrin derivatives were
      used as probes for evaluating the role of different moieties in the self-assembly
      process, providing crucial information in creating functional devices. The
      behavior of these molecules and of complexes with EuIII in some cases was studied
      in Langmuir films using surface pressure (pi) and surface potential (deltaV)
      measurements performed as a function of film compression (compression isotherms).
      For chosen cyclodextrins, Brewster angle microscopy (BAM) in monolayers was
      performed. Films formed with derivatives 1, 3, 7, and 2compl were transferred on
      mica using the Langmuir-Blodgett technique. The properties of the films deposited
      on mica were analyzed with fluorimetry and, in the case of derivative 7, using
      fringe of equal chromatic order technique (FECO). The monolayer structure and the
      fluorescence properties of the Langmuir-Blodgett films indicate that the
      derivatives studied can be used for preparing cyclodextrin-based optical devices.

PMID- 15986672
TI  - Breath figure patterns prepared by spin coating in a dry environment.
AB  - We introduce a novel method for fabricating breath figure patterns on a
      homopolymer film by spin coating of polymer solutions with various solvents. The
      homopolymers employed in this study were cellulose acetate butyrate,
      monocarboxylated end-functional polystyrene, and poly(methyl methacrylate).
      Breath figure patterns were generated even when a water-miscible solvent such as
      tetrahydrofuran (THF) was used as a solvent. We even succeeded in generating
      breath figure patterns by spin coating even under a dry environment (relative
      humidity less than 30%), when water was directly added into THF solution. With
      the combination of the spin coating method, pores with a few hundred nanometers
      to several micrometers have been generated. We found that the pore size becomes
      larger with increasing water content in THF solution and decreasing rotating
      speed. This is equivalent to increasing humidity and decreasing evaporation
      speed, respectively, in the conventional method, which is direct solvent
      evaporation under a humid environment. Thus, compared with the conventional
      method for making breath figure patterns, this method would be very convenient
      for fabricating large-scale films with various pore sizes.

PMID- 15986673
TI  - Molecular dynamics study of the interactions of ice inhibitors on the ice {001}
      surface.
AB  - The interactions of antifreeze protein (AFP) type I, antifreeze glycoproteins,
      polyvinyl pyrrolidone (PVP), and various amino acids with ice are investigated
      using Cerius2, a molecular modelling tool. Binding energies of these additives to
      a major ice crystal face {001} are computed. Binding energy comparison of
      threonine molecules (by themselves) and as threonine residues within AFP type I
      demonstrate their role in improving AFP's binding ability to the ice crystal
      face. The shifts in onset points of ice crystallization with AFP type I, PVP, and
      amino acids are measured using differential scanning calorimetry. These values
      when correlated with their respective binding energies reveal a direct
      proportionality and demonstrate AFP's effectiveness in inhibiting growth and
      nucleation of ice, over amino acids.

PMID- 15986674
TI  - Interfacial microgels formed by oppositely charged polyelectrolytes and
      surfactants. 1. Influence of polyelectrolyte molecular weight.
AB  - The synergistic adsorption and complexation of polystyrene sulfonate, PSS (a
      highly charged anionic polyelectrolyte), and dodecyltrimethylammonium bromide,
      C12TAB (a cationic surfactant), at the air-water interface can lead to
      interfacial gels that strongly influence foam-film drainage and stability. The
      formation and characteristics of these gels have been studied as a function of
      PSS molecular weight by combining surface tension, ellipsometry, and foam-film
      drainage experiments. Simultaneously the solution electromotive force has been
      measured to track the polymer-surfactant interactions in the bulk solution. It
      has been found that there is a critical molecular weight for surface gelation as
      well as for bulk precipitation and aggregation. Furthermore, we show that for the
      lowest molecular weights, PSS adsorbs with C12TAB in compact layers at the air
      water interface. In particular, for mixtures of C12TAB with the monomer compound
      of the PSS repeat unit (e.g. Mw = 208), interfacial complexation is found to be
      similar to that of catanionic mixtures (mixtures of surfactants of opposite
      charge).

PMID- 15986675
TI  - Interfacial microgels formed by oppositely charged polyelectrolytes and
      surfactants. Part 2. Influence of surfactant chain length and surfactant/polymer
      ratio.
AB  - The adsorption and complexation of polystyrene sulfonate (a highly charged
      anionic polyelectrolyte) and a series of cationic surfactants,
      alkyltrimethylammonium bromide, CnTAB, n = 8-16, at the air-water interface has
      been studied by combining surface tension and ellipsometry measurements. We find
      that increasing the chain length of the surfactant from 8 to 10 carbons leads to
      a sharp increase in adsorption of PSS/CnTAB complexes. When the surfactant tail
      length is further increased to 12 and 14 carbons, surface adsorption becomes less
      favored than macroscopic phase separation, resulting in a partial surface
      depletion. Furthermore, we find that when surface tensions are plotted against
      surfactant/monomer molar concentration ratio, all data collapse to a single
      curve. This result shows that the surfactant-polymer molar ratio, s/p, is a key
      parameter for tuning the surface activity of the complexes formed.

PMID- 15986676
TI  - Fatty acid Langmuir films on liquid mercury: X-ray and surface tension studies.
AB  - The structure and phase behavior of liquid-mercury-supported molecular films of
      fatty acids (CH3(CH2)n-2COOH, denoted CnOOH) were studied for molecular lengths 7
      < or = n < or = 24, by surface tensiometry and X-ray methods. Two qualitatively
      different film structures were found, depending on coverage. For high coverage,
      the film consists of a monolayer of roughly surface-normal molecules, showing a
      pressure-dependent sequence of structures similar, though not identical, to that
      of the corresponding water-supported Langmuir films. At low coverage, phases
      consisting of surface-parallel molecules are found, not observed on the aqueous
      subphases employed to date. In this range, a two-dimensional (2D) gas followed by
      a single and, for 14 < or = n < or = 24, also by a double layer of surface
      parallel molecules is found as coverage is increased. Depending on chain length,
      the flat-lying phases have a crystalline 2D-ordered, a smectic-like 1D-ordered,
      or a disordered in-plane structure consisting of molecular dimers. The structure
      and thermodynamics of the films are discussed.

PMID- 15986677
TI  - The structure and phase diagram of Langmuir films of alcohols on mercury.
AB  - The coverage-dependent phase behavior of molecular films of alcohols (CH3(CH2)n
      2CH2OH, denoted as CnOH) on mercury was studied for chain lengths 8 < or = n < or
      = 28, using surface tensiometry and surface specific X-ray methods. Phases with
      surface-normal-oriented molecules are found at high coverage, showing the CS, S,
      and LS phases found also on water. Phases comprising surface parallel molecules,
      which do not exist on water, are found here at low coverage. For the lowest
      coverage a two-dimensional gas phase is found, followed, upon increasing the
      coverage, by an n-dependent sequence of condensed phases of up to four layers of
      surface-parallel molecules before converting to the surface-normal phases. In
      contrast with the surface-normal phases, all of the surface-parallel phases are
      found to lack long-range order in the surface-parallel direction. Adsorption
      energies are derived from the phase diagram for the alkyl chain and the alcohol
      headgroup.

PMID- 15986678
TI  - In situ photopolymerization of a polymerizable poly(ethylene glycol)-covered
      phospholipid monolayer on a methacryloyl-terminated substrate.
AB  - We have prepared a chemically anchored monolayer of PEG (poly(ethylene glycol))
      and phospholipid mixture (PEG/phospholipid) on a methacryloyl-terminated
      substrate by in situ photopolymerization. Both monoacryloyl phospholipid
      (acryloyl-PC, 1-palmitoyl-2-[12-(acryloyloxy)dodecanoyl]-sn-glycero-3
      phosphocholine) and monoacryloyl PEG (acryloyl-PEG, 12-(acryloyloxy)dodecanoyl
      PEG) were synthesized by modifyingphospholipid and PEGwith 12-(acryloyloxy)-1
      dodecanoic acid and 12-(acryloyloxy)-1-dodecanol, respectively. The surface
      pressure-area (pi-A) isotherm showed that acryloyl-PEG molecules were stable in
      the phospholipid monolayer and that they could be evenly inserted into a
      phospholipid monolayer at the air/water interface. By adding 10 mol % acryloyl
      PEG into phosholipid vesicles, we could produce a PEG/phosholipid monolayer on
      methacryloyl-terminated substrates using vesicle fusion for 3 h. Then, this
      polymerizable PEG/phospholipid monolayer was in situ photopolymerized onto a
      methacryloyl-terminated substrate with eosin Y/triethanolamine as co-initiators.
      Optimal vesicle fusion and irradiation condition were determined with respect to
      the vesicle fusion time and duration of irradiation. As confirmed by atomic force
      microscopy and X-ray reflectivity studies, the polymerized PEG/phosholipid
      surface formed a PEG-covered phospholipid monolayer with thicknesses of 3 and 6
      nm for the base phospholipid monolayer and the covering PEG layer, respectively.
      The chemical anchoring efficiency ofpolymerized PEG and phospholipid molecules,
      which was calculated by the relative carbon ratio of each surface before and
      after methanol washing using X-ray photoelectron spectroscopy, was 98%. This
      polymerized PEG/phosholipid monolayer showed good stability in organic solution
      due to firm chemical anchoring to a solid surface.

PMID- 15986679
TI  - Highly ion conductive poly(ethylene oxide)-based solid polymer electrolytes from
      hydrogen bonding layer-by-layer assembly.
AB  - We report the development of a solid polymer electrolyte film from hydrogen
      bonding layer-by-layer (LBL) assembly that outperforms previously reported LBL
      assembled films and approaches battery integration capability. Films were
      fabricated by alternating deposition of poly(ethylene oxide) (PEO) and
      poly(acrylic acid) (PAA) layers from aqueous solutions. Film quality benefits
      from increasing PEO molecular weight even into the 10(6) range due to the
      intrinsically low PEO/PAA cross-link density. Assembly is disrupted at pH near
      the PAA ionization onset, and a potential mechanism for modulating PEO:PAA ratio
      within assembled films by manipulating pH is discussed. Ionic conductivity of 5 x
      10(-5) S/cm is achievable after short exposure to 100% relative humidity (RH) for
      plasticization. Adding free ions by exposing PEO/ PAA films to lithium salt
      solutions enhanced conductivity to greater than 10(-5) S/cm at only 52% RH and
      tentatively greater than 10(-4) S/cm at 100% RH. The excellent stability of
      PEO/PAA films even when exposed to 1.0 M salt solutions led to an exploration of
      LBL assembly with added electrolyte present in the adsorption step. Fortuitously,
      the modulation of PEO/PAA assembly by ionic strength is analogous to that of
      electrostatic LBL assembly and can be attributed to electrolyte interactions with
      PEO and PAA. Dry ionic conductivity was enhanced in films assembled in the
      presence of salt as compared to films that were merely exposed to salt after
      assembly, implying different morphologies. These results reveal clear directions
      for the evolution of these promising solid polymer electrolytes into elements
      appropriate for electrochemical power storage and generation applications.

PMID- 15986680
TI  - Interaction force between two charged plates immersed in a solution of charged
      particles. Coupling between double layer and depletion forces.
AB  - When two parallel plates are immersed in a solution of small charged particles,
      the center of the particles is excluded from a region of thickness D/2 near the
      plate, where D is their diameter. The approach which Langmuir developed for the
      double layer repulsion in the presence of an electrolyte with ions of negligible
      size is extended to the case in which one of the "ions" is a charged particle of
      finite, relatively small size. A general expression for the force generated
      between the two charged plates immersed in an electrolyte solution containing
      relatively small charged particles is derived. In this expression, only the
      electrical potential at the middle distance between the plates is required to
      calculate the force. A Poisson-Boltzmann equation which accounts for the volume
      exclusion of the charged particles in the vicinity of the surface is solved to
      obtain the electrical potential at the middle between the two plates. Starting
      from this expression, some results obtained previously for the depletion force
      acting between two plates or two spheres are rederived. For charged plates
      immersed in a solution of an electrolyte and charged small particles, the effects
      of the particle charge, particle charge sign, particle size, and volume fraction
      of the particles on the force acting between the two plates are examined.

PMID- 15986681
TI  - Pore assembled multilayers of charged polypeptides in microporous membranes for
      ion separation.
AB  - In this study, highly permeable ion-selective membranes are prepared via
      immobilization of polyelectrolyte multilayer networks within the inner pore
      structure of a microporous (pore size = 0.2 microm) support. Electrostatic layer
      by-layer assembly is achieved through alternate adsorption of cationic and
      anionic polyelectrolytes under convective flow conditions. To initiate pore
      assembly, the first layer consists of covalently bound charged polypeptides
      (poly(L-glutamic acid) (PLGA) or poly(L-lysine) (PLL)) establishing a charged
      support for subsequent adsorption. Nonstoichiometric immobilization of charged
      multilayers within a confined pore geometry leads to an enhanced volume density
      of ionizable groups in the membrane phase. This overall increase in the effective
      charge density allows for Donnan exclusion of ionic species (especially divalent
      co-ions) using microporous materials characterized by permeability values that
      exceed conventional membrane processes. Multilayer assemblies are fabricated
      using both PLGA/PLL and synthetic polyelectrolytes
      (poly(styrenesulfonate)/poly(allylamine)) in an attempt to compare the level of
      adsorption and separation properties of the resulting materials. The role of salt
      concentration in the carrier solvent on overall polyelectrolyte adsorption was
      examined to determine its effect on both solute (Cl-, SO4(2-), As(V)) and water
      transport. Constriction of the pore size induced by multilayer propagation was
      monitored through permeability measurements and dextran rejection studies at each
      stage of the deposition process.

PMID- 15986682
TI  - FTIR spectroscopic study of low temperature NO adsorption and NO + O2
      coadsorption on H-ZSM-5.
AB  - Adsorption of NO and coadsorption of NO and O2 on H-ZSM-5 have been studied at
      low and room temperature by means of FTIR spectroscopy. For better interpretation
      of the spectra, experiments involving isotopic labeled molecules have been
      performed. Low temperature adsorption of NO on H-ZSM-5 results initially in
      formation of NO which is H-bonded to the zeolite acidic hydroxyls. A second NO
      molecule is inserted into the OH-NO species at higher coverages, thus forming
      OH(NO)2 complexes. Different kinds of NO dimers are also formed. Negligible
      amounts of oxygenated compounds have been detected. In the presence of oxygen,
      the (di)nitrosyl species are oxidized very fast even at 100 K to N2O3, NO+, NO2,
      and N2O4. Different kinds of adsorbed N2O3 species have been evidenced. With
      increasing temperature, NO+ migrates and occupies cationic positions. The latter
      species interacts with NO at low temperature to give an [ONNO]+ complex. This
      reaction is used to prove that the different bands in the 2206-2180 cm(-1) region
      are also due to NO+ species.

PMID- 15986683
TI  - Surface interactions during polyelectrolyte multilayer buildup. 1. Interactions
      and layer structure in dilute electrolyte solutions.
AB  - We report the investigation of surface forces between polyelectrolyte multilayers
      of poly(allylamine hydrochloride) (PAH) and poly(styrenesulfonate sodium salt)
      (PSS) assembled on mica surfaces during film buildup using a surface force
      apparatus. Up to four polyelectrolyte layers were prepared on each surface ex
      situ, and the surface interactions were measured in 10(-4) M KBr solutions. The
      film thickness under high compressive loads (above 2000 microN/m) increased
      linearly with the number of deposited layers. In all cases, the interaction
      between identical surfaces at large separations (>100 A from contact) was
      dominated by electrostatic double-layer repulsion. By fitting DLVO theory to the
      experimental force curves, the apparent double-layer potential of the interacting
      surfaces was calculated. At shorter separations, an additional non-DLVO repulsion
      was present due to polyelectrolyte chains extending some distance from the
      surface into solution, thus generating an electrosteric type of repulsion. Forces
      between dissimilar multilayers (i.e., one of the multilayers terminated with PSS
      and the other with PAH) were attractive at large separations (30-400 A) owing to
      a combination of electrostatic attraction and polyelectrolyte bridging.

PMID- 15986684
TI  - Brewster angle microscopic observations of the Langmuir films of amphiphilic
      spiropyran during compression and under UV illumination.
AB  - The structure of the Langmuir film of an amphiphilic spiropyran, 1',3'-dihydro
      3',3'-dimethyl-6-nitro-l'-octadecyl-8-(docosanoyloxyme thyl)spiro[2H-1-benzopyran
      2,2'-(2H)-indole] (SP), is investigated using Brewster angle microscopy (BAM).
      The BAM observations show that the Langmuir film of SP can be roughly categorized
      into three regimes: a low-temperature regime at 7-13 degrees C; a medium
      temperature regime at 23-30 degrees C; a high-temperature regime at 40 degrees C.
      The low-temperature regime is characterized both by the domains that are formed
      just after the spreading and by the onset of the surface pressure when the
      domains are merged together to form continuous trilayers. In the medium
      temperature regime, a continuous monolayer film is formed after the solvent
      evaporation, followed by the growth of "embryos" with compression. Around the
      phase transition point, the "embryos" serve as the "nucleation sites" of the
      circular trilayer domains. The characteristic features of the high-temperature
      regime are similar to the ones of the medium-temperature regime except for the
      absence of a steep rise in surface pressure after the plateau region and the
      absence of the circular trilayer domains. UV illumination of the Langmuir films
      leads to the isomerization of SP into merocyanine (MC). However, J-aggregates of
      MC are formed only when the circular trilayer domains are present. On the basis
      of the above results, we present a phase diagram of the Langmuir film of SP. The
      structure and photoreaction depend strongly on the phase of the Langmuir film,
      indicating that the area/molecule is not the only decisive parameter.

PMID- 15986685
TI  - Mixed solutions of anionic and zwitterionic surfactant (Betaine): surface-tension
      isotherms, adsorption, and relaxation kinetics.
AB  - Here, we present experimental surface-tension isotherms of mixed solutions of two
      surfactants, sodium dodecyl sulfate (SDS) and cocoamidopropyl betaine (Betaine),
      measured by means of the Wilhelmy plate method. The kinetics of surface-tension
      relaxation exhibits two characteristic time scales, which have been distinguished
      to determine correctly the equilibrium surface tension. The transition from the
      zwitterionic to the cationic form of Betaine is detected by surface-tension
      measurements. Synergistic dependence of the critical micellization concentration
      on the composition of the surfactant blend is established. The experimental
      surface-tension isotherms are fitted by means of the two-component van der Waals
      model, and an excellent agreement between theory and experiment was achieved.
      Having determined the parameters of the model, we calculated different properties
      of the mixed surfactant adsorption layer at various concentrations ofSDS,
      Betaine, and salt. Such properties are the adsorptions ofthe two surfactants, the
      surface dilatational elasticity, the occupancy of the Stern layer by bound
      counterions, the surface electric potential, and so forth. In particular, the
      addition of a small amount of Betaine to SDS significantly increases the surface
      elasticity. The results could be further applied to predict the thickness and
      stability of foam films or the size of the rodlike micelles in the mixed
      solutions of SDS and Betaine.

PMID- 15986686
TI  - STM observation of alkyl-chain-assisted self-assembled monolayers of pyridine
      coordinated porphyrin rhodium chlorides.
AB  - Alkyl-chain-assisted self-assembled monolayers of pyridine-coordinated porphyrin
      rhodium chlorides were observed at the solid-liquid interface by scanning
      tunneling microscopy (STM). The resolved images at a molecular level were
      obtainable in the pure solution of pyridine-coordinated porphyrin rhodium
      chloride with four triacontyl groups [Rh(C300PP)(Cl)(Py)]. In the case of
      pyridine-coordinated porphyrin rhodium chloride with four octadecyl groups
      [Rh(C18OPP)(Cl)(Py)], the STM images were not obtainable in the pure solution of
      Rh(C18OPP)(Cl)(Py) but obtainable in the mixture containing Rh(C18OPP)(Cl)(Py)
      and free porphyrin C18OPP. On the basis of the mixed self-assembled monolayer
      analysis, the apparent difference in the adsorption free energy between
      Rh(CnOPP)(Cl)(Py) and CnOPP (deltaGapp) was calculated. The calculated deltaGapp
      values for C18OPP and C30OPP mixed systems were quite different. The disadvantage
      of the adsorption free energy of Rh(C18OPP)(Cl)(Py) makes it difficult to obtain
      molecularly resolved images of Rh(C18OPP)(Cl)(Py), and the large adsorption
      energy due to the long alkyl chains enabled us to obtain molecularly resolved
      images of Rh(C30OPP)(Cl)(Py).

PMID- 15986687
TI  - Molecular printboards: monolayers of beta-cyclodextrins on silicon oxide
      surfaces.
AB  - Monolayers of beta-cyclodextrin host molecules have been prepared on SiO2
      surfaces. An ordered and stable cyano-terminated monolayer was modified in three
      consecutive surface reactions. First, the cyanide groups were reduced to their
      corresponding free amines using Red Al as a reducing agent. Second, 1,4-phenylene
      diisothiocyanate was used to react with the amine monolayer where it acts as a
      linking molecule, exposing isothiocyanates that can be derivatized further.
      Finally, per-6-amino beta-cyclodextrin was reacted with these isothiocyanate
      functions to yield a monolayer exposing beta-cyclodextrin. All monolayers were
      characterized by contact angle measurements, ellipsometric thickness
      measurements, Brewster angle Fourier transform infrared spectroscopy, X-ray
      photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry,
      which indicate the formation of a densely packed cyclodextrin surface. It was
      demonstrated that the beta-cyclodextrin monolayer could bind suitable guest
      molecules in a reversible manner. A fluorescent molecule (1), equipped with two
      adamantyl groups for complexation, was adsorbed onto the host monolayer from
      solution to form a monolayer of guest molecules. Subsequently, the guest
      molecules were desorbed from the surface by competition with increasing beta
      cyclodextrin concentration in solution. The data were fitted using a model. An
      intrinsic binding constant of 3.3 +/- 1 x 10(5) M(-1) was obtained, which
      corresponds well to previously obtained results with a divalent guest molecule on
      beta-cyclodextrin monolayers on gold. In addition, the number of guest molecules
      bound to the host surface was determined, and a surface coverage of ca. 30% was
      found.

PMID- 15986688
TI  - Sum frequency generation studies at poly(ethylene terephthalate)/silane
      interfaces: hydrogen bond formation and molecular conformation determination.
AB  - To better understand the effects of interfacial molecular orientation on adhesion
      to plastics, the interfaces between poly(ethylene terephthalate) (PET) and
      different silane coupling agents were probed using sum frequency generation (SFG)
      vibrational spectroscopy. The polymer/air interface was dominated by the ester
      carbonyl, methylene, and phenyl groups. Upon contacting the PET film with the
      amino-functional silane 3-aminopropyltrimethoxysilane (ATMS), the ester carbonyl
      stretch shifted to a lower energy indicating the formation of hydrogen bonds
      between the polymer surface and the silane molecules. This shift was not observed
      when silanes that contained no hydrogen bond donors, such as (3-glycidoxypropyl)
      trimethoxysilane and n-butyltrimethoxysilane, were placed into contact with the
      PET surface. Further evidence of silane ordering at the interface was observed as
      vibrational peaks attributed to the C-H stretching of the silane methoxy
      headgroups dominated the PET/silane spectra. It was determined that the
      conformation of the ATMS molecules at the interface was such that the amino
      endgroups were oriented toward the interface while the methoxy headgroups were
      directed toward the silane bulk.

PMID- 15986689
TI  - The role of the electrical double layer and ion pairing on the electrochemical
      oxidation of hexachloroiridate(III) at Pt electrodes of nanometer dimensions.
AB  - The steady-state voltammetric oxidation of hexachloroiridate(III), IrCl6(3-) (1-5
      mM), in the presence and absence of an excess supporting electrolyte was
      investigated at disk- and hemispherical-shaped Pt electrodes with radii ranging
      from 48 nm to 12.5 microm. Thermodynamic, kinetic, and transport parameters that
      define the shape and magnitude of the voltammetric wave exhibit a complex
      dependence on whether a supporting electrolyte is present in the solution. First,
      the half-wave potential, E1/2, for oxidation of IrCl6(3-) shifts to more positive
      potentials in the presence of a supporting electrolyte, a consequence of the
      relative difference in the strength of ion pairing of IrCl6(3-) and IrCl6(2-) by
      the supporting electrolyte cation. E1/2 increases in the order no electrolyte < n
      tetrabutylammonium < Na+ approximately K+ approximately Ca2+, but is independent
      of the supporting electrolyte anion (Cl-, NO3-, PF6-). Second, the heterogeneous
      electron-transfer rate constant for oxidation of IrCl6(3-) increases by
      approximately an order of magnitude in the presence of a supporting electrolyte.
      Third, in the absence of electrolyte, mass transport limited currents deviate
      significantly from predicted values based on the Nernst-Planck equation, but only
      when the electrode radius is smaller than ca. 1 microm. The latter two effects
      (Frumkin and dynamic diffuse layer effects) result from the dependence of
      interfacial electrical fields and, thus, the rates of electron-transfer and ion
      migration, on the supporting electrolyte concentration. We also demonstrate that
      the theoretical shape of the voltammetric response for oxidation or reduction of
      a highly charged redox species (e.g., IrCl6(3-)) is essentially independent of
      whether a supporting electrolyte is present in the solution. This finding can
      greatly simplify the analysis of heterogeneous electron-transfer rates using
      steady-state voltammetry in low ionic strength solutions.

PMID- 15986690
TI  - Biosensing properties of diamond and carbon nanotubes.
AB  - The biochemical properties of boron-doped diamond (BDD), carbon nanofiber,
      fullerene, and multiwalled carbon nanotube (MWCNT) electrodes have been
      investigated comparatively. Physiochemical factors which affect the biosensing
      properties such as surface hydrophobicities, effective surface area, and
      intrinsic material properties are studied. Voltammetric responses of the as-grown
      thin film electrode and surface-modified electrode to biomolecules such as L
      ascorbic acid (L-AA), dopamine (DA), and uric acid are examined. As-grown MWCNT
      electrodes exhibit selective voltammetric responses to the different biomolecules
      and faster electron-transfer kinetics compared to BDD. The selective response is
      due to the considerably lower anodic potential of L-AA on MWCNT (-48 mVvs Ag/AgCl
      compared to 575 mV on BDD). This electrocatalytic response can be replicated on a
      nonselective carbon nanofiber electrode by coating it with gold nanoparticles.
      BDD has no intrinsic selective response to L-AA, and surface modification by
      anodic polarization is necessary for resolving L-AA and DA.

PMID- 15986692
TI  - Easy and efficient bonding of biomolecules to an oxide surface of silicon.
AB  - A new method is described to attach biological molecules to the surface of
      silicon. Semiconductors such as Si modified with surface-bound capture molecules
      have enormous potential for use in biosensors for which an ideal detection
      platform should be inexpensive, recognize targets rapidly with high sensitivity
      and specificity, and possess superior stability. In this process, a self
      assembled film of an organophosphonic acid is bonded to the native or synthesized
      oxide-coated Si surface as a film of the correspondingphosphonate. The
      phosphonate film is functionalized to enable covalently coupling biological
      molecules, ranging in size from small peptides to large multi-subunit proteins,
      to the Si surface. Surface modification and biomolecule coupling procedures are
      easily accomplished: all reactions can proceed in air, and most take place under
      ambient conditions. The biomolecule-modified surfaces are stable under
      physiological conditions, are selective for adhesion of specific cells types, and
      are reusable.

PMID- 15986691
TI  - The effect of polymer chain length and surface density on the adhesiveness of
      functionalized polymersomes.
AB  - Giant cell-like polymer vesicles, polymersomes, made from the diblock copolymer
      poly(ethylene oxide)-polybutadiene (PEO-PBD), have bilayer structures similar to
      the cell membrane but have superior and tunable properties for storage and
      stability. We have modified the terminal hydroxyl of the hydrophilic block with
      biotin-lysine (biocytin), a biologically derived group that imparts specific
      adhesiveness to a polymer colloid coated with avidin. The functionalized polymer
      will form vesicles, either on its own or when mixed with unmodified block
      copolymers that also form vesicles. The incorporation and mixing of the
      functionalized polymer into vesicle bilayers is measured using a fluorescent
      version ofbiocytin with confocal microscopy. The fluorescence signal associated
      with the vesicle is in proportion with the concentration of functional polymer
      added during vesicle construction. The adhesiveness of polymer vesicles
      containing functionalized biotinylated polymer to avidin coated microspheres is
      measured with micropipet aspiration. Two types of polymer vesicles were
      constructed: one where the functionalized polymer (molecular weight (MW), 10400
      Da) was longer than the surrounding unfunctionalized polymer (MW, 3600 Da) and
      one where the functionalized polymer (MW, 10400 Da) was the same length as the
      unfunctionalized polymer. In all cases, the avidin-biotin bonds form kinetically
      trapped crossbridges that impart little tension as they form but require
      significantly more tension to break. The relative length of the functionalized
      polymer on the surface of the vesicle is an important determinant for the
      adhesion of a polymer vesicle but not for the adsorption of soluble avidin.
      Greater adhesion strengths are seen where the functionalized polymer is longer
      than the surrounding polymer. The concentration of functionalized polymer at
      which adhesion is maximal depends on the relative lengths of the polymers. When
      the functionalized polymer is the same length as the surface brush of the
      polymersome membrane, the critical tension is maximal at 10 mol % functionalized
      polymer concentration. However, when the biocytin groups are attached to a
      polymer which is larger than the surface brush, the critical tension is maximal
      at 55 mol % functionalized polymer. These results indicate that polymer mixing
      and length can control the interfacial adhesion of polymer brushes and must be
      understood to tune polymersome adhesiveness.

PMID- 15986693
TI  - Ultrathin poly(N-isopropylacrylamide) grafted layer on polystyrene surfaces for
      cell adhesion/detachment control.
AB  - We investigated physicochemical properties of two types of poly(N
      isopropylacrylamide) (PIPAAm)-grafted tissue culture polystyrene (TCPS) surfaces,
      to elucidate the influential factors for thermally regulated cell adhesion and
      detachment to PIPAAm-grafted surfaces. The two types of PIPAAm-grafted surfaces
      were prepared by the electron beam polymerization method. Attenuated total
      reflection Fourier transform infrared spectroscopy revealed that amounts of the
      grafted polymers were 1.4 +/- 0.1 microg/cm2 for PIPAAm-1.4 and 2.9 +/- 0.1
      microg/cm2 for PIPAAm-2.9. Both PIPAAm-grafted surfaces showed
      hydrophobic/hydrophilic property alterations in response to temperature. However,
      PIPAAm-1.4 surfaces were more hydrophobic (cos theta = 0.21 at 37 degrees C and
      cos theta = 0.35 at 20 degrees C) than PIPAAm-2.9 (cos theta = 0.42 at 37 degrees
      C and cos theta = 0.50 at 20 degrees C) both above and below the PIPAAm's
      transition temperature. Thicknesses of the grafted PIPAAm layers were estimated
      to be 15.5 +/- 7.2 nm for PIPAAm-1.4 and 29.5 +/- 8.4 nm for PIPAAm-2.9, by the
      use of UV excimer laser and atomic force microscope. Bovine carotid artery
      endothelial cells (ECs) adhere to the surfaces of PIPAAm-1.4 and proliferate to
      form confluent cell monolayers. The cell monolayers were harvested as single cell
      sheets by temperature decrease from 37 to 20 degrees C. On the contrary, ECs did
      not adhere to the surfaces of PIPAAm-2.9. This phenomenon was correlated with an
      adsorption of cell adhesion protein, fibronectin, onto surfaces ofPIPAAm-1.4 and 
      2.9. In the case of nano-ordered thin grafted surfaces, the surface chain
      mobility is strongly influenced by the thickness of PIPAAm grafted layers because
      dehydration of PIPAAm chains should be enhanced by the hydrophobic TCPS surfaces.
      PIPAAm graft amounts, that is, thickness of the PIPAAm grafted layers, play a
      crucial role in temperature-induced hydrophilic/hydrophobic property alterations
      and cell adhesion/detachment behavior.

PMID- 15986694
TI  - Infrared detection of a phenylboronic acid terminated alkane thiol monolayer on
      gold surfaces.
AB  - Polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS)
      and infrared reflectance absorption spectroscopy (IRRAS) have been used to
      characterize the formation of a self-assembled monolayer of N-(3
      dihydroxyborylphenyl)-11-mercaptoundecanamide) (abbreviated PBA) on a gold
      surface and the subsequent binding of various sugars to the PBA adlayer through
      the phenylboronic acid moiety to form a phenylboronate ester. Vibrationally
      resonant sum frequency generation (VR-SFG) spectroscopy confirmed the ordering of
      the substituted phenyl groups of the PBA adlayer on the gold surface. Solution
      FTIR spectra and density functional theory were used to confirm the identity of
      the observed vibrational modes on the gold surface of PBA with and without bound
      sugar. The detection of the binding of glucose on the gold surface was confirmed
      in part by the presence of a C-O stretching mode of glucose and the observed O-H
      stretching mode of glucose that is shifted in position relative to the O-H
      stretching mode of boronic acid. An IR marker mode was also observed at 1734 cm(
      1) upon the binding of glucose. Additionally, changes in the peak profile of the
      B-O stretching band were observed upon binding, confirming formation of a
      phenylboronate ester on the gold surface. The binding of mannose and lactose were
      also detected primarily through the IR marker mode at approximately 1736 to 1742
      cm(-1) depending on the identity of the bound sugar.

PMID- 15986695
TI  - Isothermal desiccation and vitrification kinetics of trehalose-dextran solutions.
AB  - The promise of dried state preservation is based on the hypothesis that lowering
      molecular mobility to halt chemical reaction and deterioration rates is the
      primary factor for the long-term stability of the dried specimen. In this
      research, the feasibility of utilizing isothermal, isobaric vitrification as an
      economical alternative to the preservation technologies currently in use (mainly,
      cryopreservation and lyophilization) is explored. Desiccation and vitrification
      kinetics of model trehalose and trehalose-dextran systems were examined using
      gravimetric analysis, modulated differential scanning calorimetry, and X-ray
      crystallography. It was shown that vitrification can be achieved isothermally
      without crystallization and that vitrification of trehalose solutions can be
      significantly accelerated by incorporating high-molecular-weight dextrans.
      Additionally, it was shown that, for the same water content, the glass transition
      temperature of the trehalose-dextran solution is significantly higher than that
      of the binary trehalose solution, making the glassy state achievable and storage
      feasible.

PMID- 15986696
TI  - Adsorption of bovine alpha-lactalbumin on suspended solid nanospheres and its
      subsequent displacement studied by NMR spectroscopy.
AB  - Detailed knowledge of the adsorption-induced conformational changes of proteins
      is essential to understand the process of protein adsorption. However, not much
      information about these conformational changes is available. Here, the adsorption
      of calcium-depleted (APO)- and calcium-containing (HOLO)-bovine alpha-lactalbumin
      (BLA) on suspended solid polystyrene nanospheres and their subsequent
      displacement by a surfactant are studied by NMR spectroscopy. To our knowledge,
      this is the first time that adsorption of proteins on solid nanospheres, with
      both components present in the NMR sample, is studied by this method. High
      quality one-dimensional and two-dimensional 1H NMR spectra of nonadsorbed APO-
      and HOLO-BLA in the presence of BLA- and/or surfactant-covered solid polystyrene
      nanospheres in suspension are obtained using standard NMR procedures. BLA and
      surfactant molecules that are adsorbed on the polystyrene nanospheres give rise
      to extremely broadened proton resonances. This can be exploited to determine the
      amount of adsorbed protein and of adsorbed surfactant in a system containing
      protein, nanospheres, and surfactant, without disturbing the equilibrium of the
      system. Two-dimensional 1H NMR spectroscopy shows that the chemical shifts of the
      backbone amide protons of HOLO-BLA after its adsorption and subsequent
      displacement from polystyrene nanospheres by the surfactant 3-[(3
      cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) are identical to
      those of native HOLO-BLA. The adsorption-induced unfolding of BLA to a molten
      globule state on polystyrene nanospheres is thus fully reversible at the residue
      level upon CHAPS-induced displacement of BLA. The latter is the now fulfilled
      essential requirement that enables the future indirect study, at the residue
      level, of the conformational characteristics of BLA adsorbed on polystyrene
      nanospheres by hydrogen/deuterium exchange and NMR spectroscopy. The results
      presented show that NMR spectroscopy is clearly feasible to study the adsorption
      of BLA on suspended polystyrene nanospheres. This technique should be applicable
      to the study of the adsorption of other proteins on other surfaces as well.

PMID- 15986697
TI  - Optical properties of an immobilized DNA monolayer from 255 to 700 nm.
AB  - The real (n) and imaginary (k) refractive indices of an immobilized monolayer of
      27 nucleotide (nt) single stranded DNA (ssDNA) and the corresponding double
      stranded DNA (dsDNA) are measured in the 255-700 nm range. Multiple techniques
      are used to obtain consistent estimation. The coverage is approximately 6.5% with
      an average interchain distance of tethered ssDNA molecules of approximately 11.8
      nm, which is significantly larger than the "footprint" of the chain on the
      surface. The measured increase in n by approximately 5% between the ssDNA and the
      dsDNA is 20% smaller than the expected change due to doubling of the molecular
      weight. The change in k is not significant, indicating that the electron
      delocalization effect expected in dsDNA due to base pair stacking is not
      important at optical frequencies.

PMID- 15986699
TI  - Alkanethiol-induced structural rearrangements in silica-gold core-shell-type
      nanoparticle clusters: an opportunity for chemical sensor engineering.
AB  - Electrostatically bonded SiO2.Au nanoparticle clusters form by reaction of 3
      aminopropylsilane-modified SiO2 spheres (470 nm) with citrate-coated gold
      nanoparticles (9.7 nm) in water. Reaction of the clusters with 0.01 M KBr or HCl
      solution induces desorption of the gold nanoparticles within minutes. Reaction of
      the clusters with alkanethiols CnH2n+1SH (n = 2-18) at 80 degrees C causes the
      gold nanoparticles to form stringlike gold nanoparticle structures for thiols
      with short alkane groups (n = 2, 3, 4) and hexagonally packed arrays of gold
      nanoparticles for thiols with long alkane groups (n = 5-18) on the silica
      surfaces. The structural changes indicate that the bonding between Au and SiO2
      nanoparticles has changed from electrostatic to van der Waals. Elemental analyses
      show that the reaction with hexanethiol does not affect the Au/Si/O composition
      of the SiO2.Au cluster, and Raman spectra on the hexanethiol-reacted cluster
      indicate the formation of a thiol SAM on the gold nanoparticles. The thiol
      reacted SiO2.Au clusters display characteristic shifts of the absorption maxima
      in the visible spectra, and there is an inverse relation between these shifts and
      the lengths of the alkyl groups in the thiols. This relationship can be
      understood in terms of the free electron model for metals. The use of SiO2.Au
      nanoparticle clusters as coulometric sensors for the qualitative detection of
      thiols is discussed.

PMID- 15986698
TI  - Modification of beta-lactoglobulin by oligofructose: impact on protein adsorption
      at the air-water interface.
AB  - Maillard products of beta-lactoglobulin (betaLg) and fructose oligosaccharide
      (FOS) were obtained in different degrees of modification depending on incubation
      time and pH. By use of a variety of biochemical and spectroscopic tools, it was
      demonstrated that the modification at limited degrees does not significantly
      affect the secondary, tertiary, and quaternary structure of betaLg. The
      consequence of the modification on the thermodynamics of the protein was studied
      using differential scanning calorimetry, circular dichroism, and by monitoring
      the fluorescence intensity of protein samples with different concentrations of
      guanidine-HCl. The modification leads to lowering of the denaturation temperature
      by 5 degrees C and a reduction of the free energy of stabilization of about 30%.
      Ellipsometry and drop tensiometry demonstrated that upon adsorption to air-water
      interfaces in equilibrium modified betaLg exerts a lower surface pressure than
      native betaLg (16 versus 22 mN/m). Moreover, the surface elastic modulus
      increased with increasing surface pressure but reached significantly smaller
      values in the case of FOS-betaLg. Compared to native betaLg, modification of the
      protein with oligofructose moieties results in higher surface loads and thicker
      surface layers. The consequences of these altered surface rheological properties
      are discussed in view of the functional behavior in technological applications.

PMID- 15986700
TI  - Surface control of activated carbon fiber by growth of carbon nanofiber.
AB  - Carbon nanofiber/activated carbon fiber (CNF/ACF) composites with multifunctional
      surfaces were prepared through catalytic growth of CNFs on an ACF. Because of
      selective deposition of catalyst particles in ACF micropores, partial oxidation
      of ACF after catalyst impregnation was a critical step to control the surface
      area of the CNF/ACF composites, of which the surface functions can be
      synergistically performed by both the microporous surface of ACF and free edges
      of CNFs. CNF/ACF composites of this study are expected to provide an improved
      performance in SOx or NOx removal.

PMID- 15986701
TI  - Electron-transfer reactions and functionalization of cytochrome P450cam
      monooxygenase system in reverse micelles.
AB  - Enzyme-based electron-transfer reactions involved in the cytochrome P450
      monooxygenase system were investigated in nanostructural reverse micelles. A
      bacterial flavoprotein, putidaredoxin reductase (PdR), was activated and shown to
      be capable of catalyzing the electron transport from NADH to electron-carrier
      proteins such as cytochrome b5 (tCyt-b5) and putidaredoxin (Pdx) in reverse
      micelles. Ferric tCyt-b5 in reverse micelles was effectively converted to its
      ferrous form by the exogenous addition of separately prepared reverse micellar
      solution harboring PdR and NADH. The fact that direct interactions of
      macromolecular proteins should be possible in the reverse micellar system
      encouraged us to functionalize a multicomponent monooxygenase system composed of
      the bacterial cytochrome P450cam (P450cam), putidaredoxin (Pdx), and PdR in
      reverse micelles. The successful camphor hydroxylation reaction catalyzed by
      P450cam was significantly dependent on the coexistence of Pdx, PdR, and NADH but
      not H2O2, suggesting that the oxygen-transfer reactions proceeded via a
      "monooxygenation" mechanism. This is the first report of a multicomponent
      cytochrome P450 system exhibiting enzymatic activity in organic media.

PMID- 15986702
TI  - Tailoring the surface properties of poly(dimethylsiloxane) microfluidic devices.
AB  - Poly(dimethylsiloxane) (PDMS) is an attractive material for microelectrophoretic
      applications because of its ease of fabrication, low cost, and optical
      transparency. However, its use remains limited compared to that of glass. A major
      reason is the difficulty of tailoring the surface properties of PDMS. We
      demonstrate UV grafting of co-mixed monomers to customize the surface properties
      of PDMS microfluidic channels in a simple one-step process. By co-mixing a
      neutral monomer with a charged monomer in different ratios, properties between
      those of the neutral monomer and those of the charged monomer could be selected.
      Mixtures of four different neutral monomers and two different charged monomers
      were grafted onto PDMS surfaces. Functional microchannels were fabricated from
      PDMS halves grafted with each of the different mixtures. By varying the
      concentration of the charged monomer, microchannels with electrophoretic
      mobilities between +4 x 10(-4) cm2/(V s) and -2 x 10(-4) cm2/(V s) were
      attainable. In addition, both the contact angle of the coated surfaces and the
      electrophoretic mobility of the coated microchannels were stable over time and
      upon exposure to air. By carefully selecting mixtures ofmonomers with the
      appropriate properties, it may be possible to tailor the surface of PDMS for a
      large number of different applications.

PMID- 15986703
TI  - Human serum albumin self-assembly on weak polyelectrolyte multilayer films
      structurally modified by pH changes.
AB  - Adsorption of proteins onto film surfaces built up layer by layer from oppositely
      charged polyelectrolytes is a complex phenomenon, governed by electrostatic
      forces, hydrogen bonds, and hydrophobic interactions. The amounts of the
      interacting charges, however, both in polyelectrolytes and in proteins adsorbed
      on such films are a function of the pH of the solution. In addition, the number
      and the accessibility of free charges in proteins depend on the secondary
      structure of the protein. The subtle interplay of all these factors determines
      the adsorption of the proteins onto the polyelectrolyte film surfaces. We
      investigated the effect of these parameters for polyelectrolyte films built up
      from weak "protein-like" polyelectrolytes (i.e., polypeptides), poly(L-lysine)
      (PLL), and poly(glutamic acid) (PGA) and for the adsorption of human serum
      albumin (HSA) onto these films in the pH range 3.0-10.5. It was found that the
      buildup of the polyelectrolyte films is not a simple function of the pure charges
      of the individual polyelectrolytes, as estimated from their respective pKa
      values. The adsorption of HSA onto (PLL/PGA)n films depended strongly on the
      polyelectrolyte terminating the film. For PLL-terminated polyelectrolyte films,
      at low pH, repulsion, as expected, is limiting the adsorption of HSA (having net
      positive charge below pH 4.6) since PLL is also positively charged here. At high
      pH values, an unexpected HSA uptake was found on the PGA-ending films, even when
      both PGA and HSA were negatively charged. It is suggested that the higher surface
      rugosity and the decrease of the alpha-helix content at basic pH values (making
      accessible certain charged groups of the protein for interactions with the
      polyelectrolyte film) could explain this behavior.

PMID- 15986704
TI  - Templateless room-temperature assembly of nanowire networks from nanoparticles.
AB  - We demonstrate a new, room-temperature approach to assemble two-dimensional and
      three-dimensional networks of gold nanowires by agitating nanoparticles in a
      toluene-aqueous mixture, without the use of templates. The nanowires have a
      uniform diameter of about 5 nm and consist of coalesced face-centered cubic
      nanocrystals. Toluene molecules passivate the gold surfaces during nanoparticle
      coalescence, rendering the nanowires hydrophobic and enabling their transfer into
      the toluene layer. Such templateless low-temperature assembly of mesostructures
      from nanoscale building blocks open up new possibilities for creating porous self
      supporting nanocatalysts, nanowires for device interconnection, and low-density
      high-strength nanofillers for composites.

PMID- 15986705
TI  - Self-assembly patterning of colloidal crystals constructed from opal structure or
      NaCl structure.
AB  - We developed a novel self-assembly process to fabricate an orderly array of
      particle wires constructed from a close-packed colloidal crystal without
      preparation of patterned templates. A substrate was immersed vertically into a
      SiO2 colloidal solution, and the liquid surface moved downward upon evaporation
      of solution. Particles formed a mono-/multiparticle layer, which was cut by the
      periodic drop-off of solution. The orderly array of particle wires was
      successfully fabricated, showing the suitability of the self-assembly process for
      the fabrication of nano-/microstructures constructed from nano-/microparticles or
      blocks. The mechanism of the assembly process and control of thickness, width,
      and interval of particle wires were further discussed. Moreover, an array of
      particle wires constructed not from close-packed face-centered cubic (or
      hexagonal close packed) structure but from two kinds of particles was realized to
      fabricate an array of particle wires with NaCl structure by this self-assembly
      process.

PMID- 15986706
TI  - Selective electroless metal deposition using microcontact printing of phosphine
      phosphonic acid inks.
AB  - We report a low-cost approach to selectively deposit films of nickel and copper
      on glass substrates. Our approach uses microcontact printing of organic inks
      containing phosphonic acid groups to bind the ink to a glass substrate and
      phosphine groups to bind a colloidal catalyst that initiates electroless
      metallization. We demonstrate this procedure by fabricating patterned nickel and
      copper films with areas as large as 15 cm2 and minimum feature sizes of
      approximately 2 microm. We present studies on the use of two ink types, an
      oligomer and a bifunctional molecule, and demonstrate that pattern quality and
      adhesion of the metallized films depends on the molecular weight of the ink and
      the ratio of phosphine and phosphonic acid groups.

PMID- 15986707
TI  - Investigation of the role of the interplay between water and temperature on the
      growth of alkylsiloxane submonolayers on silicon.
AB  - We have investigated the influence of the interplay of the temperature and the
      water concentration in the adsorption solution on the growth of self-assembled
      monolayers on silicon using octadecyltrichlorosilane as the precursor. Toluene
      has been used as the solvent. The morphology of the submonolayer films has been
      investigated by atomic force microscopy (AFM). The surface coverages have been
      determined both with ellipsometry and through quantitative evaluation of AFM
      images. The size distribution of species in the precursor solution has been
      studied with dynamic light scattering. The influence of water concentrations
      between 8 and 18 mmol/L has been investigated in the temperature range from 2 to
      35 degrees C. Dynamic light scattering revealed a unimodal size distribution of
      ordered aggregates in solution with a hydrodynamic radius of 200 nm regardless of
      the temperature and water concentration. However, formation of these features was
      faster at higher water contents and lower temperatures. Moreover, a
      characteristic temperature, which was higher for higher water concentrations, was
      found, above which such aggregates could not be detected anymore. Below this
      temperature an increase of the aggregate concentration has been observed until a
      plateau had been reached within a temperature range of approximately 5 degrees C.
      AFM measurements and ellipsometry on the corresponding submonolayer films showed
      that this temperature range is also associated with a transition from fast growth
      via characteristic fractally shaped islands to comparatively slow homogeneous
      growth via adsorption of individual molecules. The results are discussed in terms
      of diffusion and adsorption limitations.

PMID- 15986708
TI  - Study of copper sulfide crystallization in PEO-SDS solutions.
AB  - The crystallization of copper sulfide in aqueous supersaturated solutions in the
      presence of the polymer poly(ethylene oxide), PEO, and the surfactant sodium
      dodecyl sulfate, SDS, was investigated. In these systems, copper sulfide
      precipitation competes with the reaction between copper cations and dodecyl
      sulfate anions. The competition of the two reactions may affect the reaction
      products significantly; therefore it is important to study the properties of the
      surfactant salt, copper dodecyl sulfate (Cu(DS)2), in detail. The thermodynamic
      solubility constant of Cu(DS)2 was measured at 8 degrees C and was equal to (2.4
      +/- 0.4) x 10(-10) M3. The Krafft point of Cu(DS)2 and its solubility curve
      (precipitation temperature for a range of concentrations) were also measured. The
      latter was found to be very close to room temperature. Temperature is thus a very
      significant parameter in these systems and must be carefully controlled in all
      experiments. The crystallization of copper sulfide in PEO-SDS solutions was
      investigated in solutions with compositions above and below the solubility curve.
      Copper sulfide nanoparticles predominate and are stabilized at temperatures above
      the solubility curve. Surprisingly, at temperatures below the solubility curve
      CuxS coexists with Cu(DS)2, which appears in the form of lamellar crystals. The
      system is further complicated by the presence of at least two different types of
      copper sulfides corresponding to different oxidation states of copper. Our
      results suggest that the predominance of Cu(DS)2 at lower temperatures is due to
      its limited solubility and is modified by the CuI/CuII redox equilibrium in
      combination with the solution pH.

PMID- 15986709
TI  - Polymer size and concentration effects on the size of gold nanoparticles capped
      by polymeric thiols.
AB  - Gold nanoparticles stabilized by thiol-terminated poly(ethylene glycol)
      monomethyl ethers with molecular weights ranging from 350 to 2000 have been
      prepared at thiol-to-gold molar ratios ranging from 3:1 to 1:8. Particle size
      distributions have been constructed for these particles from transmission
      electron microscopy images of hundreds of particles for each variation in
      synthetic conditions. The mean diameters of these particles range from 1.5 to 3.2
      nm, with a slight increase in particle size with decreasing thiol content; these
      particles are smaller than those prepared using alkanethiols at similar thiol-to
      gold ratios. Particles prepared under thiol-poor conditions exhibit much greater
      polydispersity than those prepared under thiol-rich conditions and include
      numerically rare large-particle outliers that contain much of the gold in the
      sample. The mean diameters of the gold nanoparticles decrease slightly with
      increasing polymer weight, especially under thiol-rich conditions. A simple model
      is developed to predict the trends in nanoparticle diameter that would result
      were the polymer's steric bulk protecting the nanoparticles from additional
      growth the principal factor controlling nanoparticle size in this system. This
      model predicts a much stronger dependence on thiol concentration than has been
      experimentally observed and a dependence on polymer molecular weight opposite to
      that experimentally observed. This suggests that the polymers' steric bulk is not
      the principal reason that these polymers yield smaller nanoparticles than
      alkanethiols at similar thiol-to-gold ratios. It is instead proposed that polar
      polymers may yield small nanoparticles by accelerating particle nucleation via
      coordination between functional groups in the polymer and atomic gold.

PMID- 15986710
TI  - Synthesis, testing, and characterization of a novel Nafion membrane with superior
      performance in photoassisted immobilized Fenton catalysis.
AB  - A new type of Nafion/Fe structured membrane ensuring faster kinetics, higher
      efficiency, and mechanical properties has been prepared and will be compared in
      its performance with the Fe-exchanged commercial Dupont 117 Nafion/Fe membrane
      during the abatement of model organic compounds. During the casting of the
      laboratory Nafion sample, the iron ions were introduced directly into the Nafion
      oligomer solution. This novel laboratory Nafion/Fe was tested as an immobilized
      catalyst in the degradation of several toxic pollutants showing a faster
      photoassisted degradation kinetics and a wider effective photocatalytic pH range
      compared to the Fe-exchanged commercial Dupont 117 Nafion/Fe membrane. When
      carrying out Ar ion sputtering of the 50 topmost catalyst layers, evidence is
      presented by X-ray photoelectron spectroscopy that Fe ions are found in the inner
      Nafion layers and seem to be responsible for the immobilized photoassisted Fenton
      processes leading to the degradation of 4-chorophenol (4-CP) taken as a model
      organic pollutant for the degradation process reported in this study. In the
      laboratory sample, the iron oxy/hydroxy Nafion moiety undergoes a transition to a
      more stable Nafion/Fe species during 4-CP degradation as determined by X-ray
      diffraction. This more stable form shows a higher iron dispersion and
      crystallinity compared to the fresh sample and is stabilized by the Nafion matrix
      avoiding the formation of separate iron phases. By infrared absorption (Fourier
      transform infrared), evidence is presented for the band of akaganeite-like
      species at 870 cm(-1) on the laboratory Nafion/Fe sample. This band disappears
      after 4-CP degradation because of the formation of the more highly dispersed iron
      species. Sputtering experiments show a decrease of F-containing groups in the
      laboratory Nafion/Fe samples closer to the catalyst upper layer while the amounts
      of Fe, C, and in particular O species increase in the topmost layer(s). In
      particular, the oxygenated species develop in the Nafion/Fe up to approximately
      50 A below the catalyst surface. These species remain stable during the long-term
      Nafion/Fe degradation of 4-CP. Dynamo-mechanical analysis performed on laboratory
      Nafion/ Fe membrane samples revealed that these membranes possessed a greater
      mechanical modulus and resistance than the commercial Dupont 117 Nafion membrane.

PMID- 15986711
TI  - Rotational diffusivity of fractal clusters.
AB  - The rotational diffusion behavior of fractal clusters generated through an off
      lattice cluster-cluster aggregation algorithm in both diffusion-limited cluster
      aggregation and reaction-limited cluster aggregation conditions is investigated.
      The extended Kirkwood-Riseman theory (Garcia de la Torre et al., Macromolecules,
      1987) is used to estimate the cluster rotational diffusion tensor. The three
      eigenvalues of this tensor, which correspond to the three main rotational
      diffusivity values of the cluster, have been computed for each generated cluster.
      Once the eigenvalues have been sorted in ascending order, each of them has been
      averaged over several thousands of clusters. It is found that one of the three
      main average rotational diffusivities is substantially larger than the other two,
      indicating significant anisotropy of fractal clusters. Moreover, a rotational
      hydrodynamic radius Rh,r has been determined on the basis of the mean value of
      the three average rotational diffusivities, which is about 25% larger than the
      mean translational hydrodynamic radius Rh calculated through the same Kirkwood
      Riseman theory. Finally, the obtained Rh,r values have been applied to interpret
      dynamic light scattering data from aggregating colloidal systems and to
      investigate the reliability of the assumption, Rh = Rh,r, typically made in the
      literature.

PMID- 15986712
TI  - Topographic SU-8 substrates for immobilization of three-dimensional nanotube
      vesicle networks.

PMID- 15986713
TI  - Formation of cadmium sulfide nanoparticles in reverse micelles: extreme
      sensitivity to preparation procedure.

PMID- 15986714
TI  - Epidemiologic analysis of alcohol and tobacco use.
AB  - Epidemiologists have conducted nationwide surveys, such as the National Household
      Survey on Drug Abuse (NHSDA) and the National Comorbidity Survey (NCS), to
      estimate the prevalence of either the individual or the concurrent consumption of
      and dependence on alcohol and tobacco. These estimates indicated that for both
      alcohol and tobacco, use was already relatively high among the youngest
      respondents, peaked among young adults, and declined in older age groups. A
      similar pattern existed for concurrent alcohol and tobacco use. Moreover, these
      estimates showed only moderate gender differences. With respect to dependence,
      the age-related prevalence patterns differed somewhat for alcohol and tobacco,
      with the prevalence of tobacco dependence relatively lower among the youngest
      respondents compared with the prevalence of alcohol dependence. The age-related
      pattern for concurrent alcohol and tobacco dependence was similar to that found
      for tobacco dependence.

PMID- 15986715
TI  - Smoking and the genetic contribution to alcohol-dependence risk.
AB  - Genes influence a person's risk of becoming a smoker as well as the risk of
      alcohol dependence. Because substantially higher rates of smoking are observed in
      alcoholics than in control groups, uncovering the mechanisms underlying this
      association may have important implications for both treatment and prevention.
      Data analyses from the 1981 Australian twin panel cohort confirm a positive
      genetic correlation between regular smoking and the risk of alcohol dependence
      that remains significant, even when sociodemographic and personality variables as
      well as histories of other psychopathologies are taken into account. Acute or
      chronic effects of smoking on subjective responses to alcohol may play a role in
      this association.

PMID- 15986716
TI  - Behavioral mechanisms underlying the link between smoking and drinking.
AB  - Many people use both alcohol and nicotine (i.e., cigarettes and other tobacco
      products). The behavioral effects of these two drugs differ, and they do not act
      on the same target sites in the brain, although they may share, or partly share,
      certain properties. The initiation of alcohol or nicotine use may be precipitated
      by similar personality characteristics in the user, such as impulsivity and
      sensation seeking. Moreover, the mechanisms underlying the development of
      dependence may be similar for alcohol and nicotine. Thus, certain factors, such
      as reinforcing drug effects, conditioning processes, automatic behavior, and
      stress, may influence the development of dependence on both drugs. Other factors,
      such as tolerance and sensitization to the drugs' actions and the development of
      withdrawal symptoms, may also contribute to dependence. This review discusses the
      actions of the two drugs on certain brain chemical (i.e., neurotransmitter)
      systems and the extent to which the effects of the two drugs may interact.

PMID- 15986717
TI  - Sociocultural influences on smoking and drinking.
AB  - Numerous research studies have shown that sociocultural factors influence the
      initiation and continued use of alcohol and tobacco among adolescents and adults.
      Few studies have examined the effects of sociocultural factors on the tendency of
      smokers to drink and drinkers to smoke. However, the limited evidence available
      suggests that such factors exist and that the strength of the association between
      alcohol and tobacco use behaviors varies with the levels of alcohol use. Public
      health interventions focused on concurrent tobacco and alcohol use could yield
      further reductions in the morbidity and mortality associated with these
      substances.

PMID- 15986718
TI  - Co-occurring risk factors for alcohol dependence and habitual smoking.
AB  - Smoking and alcohol dependence frequently occur together, and both behaviors are
      determined in part by genetic influences. The Collaborative Study on the Genetics
      of Alcoholism (COGA), which is investigating the genetic factors contributing to
      alcohol dependence, also allows for analyses of the genetic factors determining
      smoking. Using a sample comprised of alcoholics and their closest (i.e., first
      degree) relatives as well as a community-based control sample, COGA investigators
      found that both alcohol dependence and habitual smoking were transmitted within
      families. This familial transmission resulted from both common and drug-specific
      influences, which likely include genetic factors. Further genetic studies (i.e.,
      candidate gene studies and genomic screening approaches) have identified several
      DNA regions that may contain genes that confer a susceptibility for alcoholism.
      Some of those genes also may contribute to the risk for habitual smoking.

PMID- 15986719
TI  - The effects of tobacco use during and after pregnancy on exposed children.
AB  - Alcohol and tobacco use during pregnancy have both been associated with a number
      of adverse effects on the growth, cognitive development, and behavior of the
      exposed child. Understanding the effects of prenatal tobacco exposure allows
      researchers to identify those characteristics that are uniquely related to
      tobacco and those that are affected by alcohol exposure. This research, along
      with studies on the effects of alcohol use during pregnancy, has implications for
      preventing various types of substance use during pregnancy and for treating
      children affected by prenatal substance use.

PMID- 15986720
TI  - Preventing alcohol and tobacco use through life skills training.
AB  - Rates of drinking and smoking increase among high school students as they age.
      Therefore, prevention programs that target youth either before or during junior
      high school may help prevent alcohol, tobacco, and other drug (ATOD) use during
      high school. Life skills training (LST) is a school-based approach designed to
      prevent ATOD use among youth by influencing their knowledge and attitudes about
      ATODs, by teaching skills for resisting social pressures to use ATODs, and by
      helping students develop personal self-management and social skills. Researchers
      have studied this program's effectiveness in preventing use of various substances
      among varied populations.

PMID- 15986721
TI  - Evidence based medicine in neurological rehabilitation--a critical review.

PMID- 15986722
TI  - Quality management in traumatic brain injury (TBI) lessons from the prospective
      study in 6.800 patients after acute TBI in respect of neurorehabilitation.
AB  - Preliminary results on epidemiology, acute hospital care, and neurorehabilitation
      of TBI are presented of the first ever prospective controlled German study to
      analyse the use of regional structures and quality management as provided by the
      German social healthcare system. The sum of inhabitants in Hannover and Munster
      area was 2,114 million. Within an area of 100 kilometres diameter each. 6.783
      acute TBI (58% male) were admitted for acute treatment from March 2000 to 2001.
      Definition of acute TBI was according to the ICD 10 S-02, S-04, S-06, S-07, S-09
      in combination with dizziness or vomiting; retrograde or anterograde amnesia,
      impaired consciousness, skull fracture, and/or focal neurological impairment. The
      incidence was 321/100.000 population. Cause of TBI was traffic accident in 26%,
      during leisure time 35%, at home 30% and at work 15%. Initial GCS (emergency
      room) was only assessed in 3.731 TBI (=55%). Out of those 3.395 = 90,9% were
      mild, 145 = 3,9% were moderate, and 191 = 5,2% severe TBI. 28% of 6.783 patients
      were <1 to 15 years, 18% > 65 years of age. The number admitted to hospital
      treatment is 5.221 = 77%, of whom 72 patients (=1,4%) died caused by TBI. One
      year follow-up in 4.307 TBI patients (=63.5%) revealed that only 258 patients
      (=3,8%) received neurorehabilitation (73% male), but 68% within one month of
      injury. Five percent of these patients were <16 years of age, 25% > 65 years.
      Early rehabilitation "B" was performed in 100 patients (=39%), 19% within one
      week following TBI. The management of frequent complications in 148 patients
      (=57%) and the high number of one or more different consultations (n = 196)
      confirmed the author's concept for early neurosurgical rehabilitation in TBI when
      rehabilitation centres were compared regarding GCS and GOS: Early GOS 1 = 4%; GOS
      2 = 2,7%, GOS 3 = 37,3%, GOS 4 = 26,7%, GOS 5 = 29,3%, final GOS scores were 1 =
      1,2%, 2 = 1,7%, 3 = 21,8%, 4 = 36,2%, and 5 = 39,1% of all patients at the end of
      rehabilitation. Mean duration for both "B" and "C" was 41 days compared to 80
      days for "D" and "E". An assessment of both GCS and GOS was insufficient.

PMID- 15986723
TI  - Posttraumatic epilepsy with special emphasis on prophylaxis and prevention.
AB  - Posttraumatic epileptic seizures have an incidence of about 10% in series of
      severe head injuries. Control of "early seizures", i.e. those occurring in the
      first week after injury, is mandatory. Attacks, especially if recurrent, may add
      secondary damage to the injured brain: intravenous phenythoin with therapeutic
      plasma level allows control of the attacks. Seizures occurring months or years
      after injury are called "late seizures": recurring "late seizures" make up the
      clinical syndrome of "posttraumatic epilepsy". "Prophylaxis" should mean that
      drug treatment, given for a more or less prolonged period of time, blocks
      permanently the ripening of the epileptogenic foci avoiding the occurrence of
      seizures. In animal "prophylaxis" by antiepileptic drugs seems efficacious in
      many experimental models including iron induced epilepsy which is considered a
      model of posttraumatic epilepsy and vice versa. In the human being "prophylaxis"
      has been attempted with: phenytoin, phenobarbital, carbamazepine, valproate but
      without success. During treatment period the occurrence of seizures is prevented
      but, after discontinuation of the drug, seizures occur just as in non treated
      patients. The ripening of the epileptic focus in posttraumatic epilepsy, as in
      iron induced epilepsy, seems to be due to a cascade of events beginning with
      haemorrhage, haemolysis, iron or heme compound liberation, free radical
      formation, peroxidation and cell death. Experimentally free radical scavengers
      and antiperoxidants have marked prophylactic effect. Some of them (phosphate
      diester of vitamin E and C, melatonin, vanillyl alcohol) may be employed in
      clinical practice, but up to date there is no controlled study in human beings.

PMID- 15986724
TI  - Swallowing therapy--a prospective study on patients with neurogenic dysphagia due
      to unilateral paresis of the vagal nerve, Avellis' syndrome, Wallenberg's
      syndrome, posterior fossa tumours and cerebellar hemorrhage.
AB  - BACKGROUND: No studies exist dealing with the outcome of dysphagic patients with
      posterior fossa (IV. ventricle) tumours (PFT) or cerebellar hemorrhage (CH), and
      the outcome of patients with Wallenberg's syndrome (WS) after functional
      swallowing therapy (FST) has so far not been studied in detail. Patients and
      methods. 208 patients with neurogenic dysphagia (ND) who were consecutively
      admitted for functional swallowing therapy (FST) over a 3 year period to our
      hospital were examined clinically, by use of a videofluoroscopic swallowing study
      (VFSS) and/or fibreoptic evaluation of swallowing (FEES). The most frequent
      etiology was stroke (48%), followed by CNS tumours (13%). In the present study we
      defined three groups. Group 1 comprised 8 patients with PFT or CH. Group 2
      consisted of 27 patients with WS, which was the leading cause among patients with
      non-hemispheric stroke. Since in WS a vagal nerve paresis due to affection of the
      Nucleus ambiguus occurs, 8 patients with Avellis' syndrome or unilateral paresis
      of the vagal nerve served as controls and were defined as group 3. Findings. In
      the three groups, functional feeding status showed significant improvement after
      FST comprising methods of restitution, compensation and adaptation, each of which
      were applied in more than 80% of patients. Outcome was, however, significantly
      worse in group 1 as compared to group 2 and in group 2 as compared to group 3.
      Dysfunction of the upper esophageal sphincter and reflex triggering were
      significantly more severely disturbed in groups 1 and 2 as compared to group 3.
      Group 1 showed significantly more severe disturbances of the oral phase as
      compared to groups 2 and 3. After FST, more than 50% (5/8) of group 1 and 30%
      (8/27) of WS patients (group 2) were dependent on tube feeding, whereas all
      patients of group 3 were full-oral feeders. Interpretation. This is the first
      study dealing with the outcome of dysphagic patients with PFT or CH. Based on our
      results it can be assumed that in these patients pressure is exerted on both
      dorsomedial central pattern generators (DMCPGs) for swallowing in a posterior
      anterior direction. Due to the importance of the DMCPGs for swallowing, bilateral
      (and often MRI-invisible) lesions seem to be very harmful. For a better
      understanding of the pathomechanism responsible for ND in patients with PFT or
      CH, modern imaging methods such as proton magnetic resonance spectroscopy should
      be used for studying metabolic changes in the dorsal medulla in the future. Since
      the outcome of patients with WS with regard to dependence of tube feeding was not
      associated with the site or size of the lesion, it may due to the individual
      asymmetry of the swallowing-dominant forebrain hemisphere - depend on the side of
      the medullary infarction.

PMID- 15986725
TI  - Impaired self-awareness after moderately severe to severe traumatic brain injury.
AB  - Patients with moderately severe to severe traumatic brain injury (TBI) can
      demonstrate disturbances in self-awareness several months or years after injury.
      Patients may underreport cognitive and behavioral difficulties, which are the
      true residuals of their brain injury. Increasingly, research indicates that the
      residuals of these disturbances in consciousness greatly affect the process and
      outcome of rehabilitation. A recent model for conceptualizing disturbances of
      self-awareness after various forms of brain injury is reviewed.

PMID- 15986726
TI  - Assessment of health-related quality of life in persons after traumatic brain
      injury--development of the Qolibri, a specific measure.
AB  - BACKGROUND: Health-related quality of life (HRQOL) associated or not with the
      measurement of neuropsychological functioning is a relatively new outcome
      variable in the field of traumatic brain injury (TBI). In both cases, accuracy
      and precision are increased in outcome estimation. Validation of generic, cross
      culturally (cc) administered HRQOL measures in persons after TBI is not yet well
      established. Disease-specific HRQOL instruments do not exist in an international
      context. The objective here is to present the TBI consensus group's (QOLIBRI
      Group) approach in cc development of a specific HRQOL measure--the QOLIBRI
      (Quality of Life after Brain Injury). METHODS: Special issues of TBI-specific
      instrument creation will be highlighted as well as cc questionnaire construction,
      development, translation and psychometric testing. RESULTS: The validation
      process of the preliminary version of the disease-specific QOLIBRI in 15
      countries and 13 languages will be described. The QOLIBRI assesses HRQOL within
      six domains (physical condition, thinking activities, feelings and emotions,
      functioning in daily life, relationships and social/leisure activities, current
      situation and future prospects). The QOLIBRI integrates disease-specific issues
      of TBI patients, i.e. cognition, existential aspects (as the sense of self) etc.,
      which are missing in generic tools. CONCLUSION: In TBI patients, generic and
      disease-specific aspects of HRQOL need to be assessed with measures of adequate
      psychometric quality, applicable across different populations and cultural
      conditions. The QOLIBRI is a promising instrument for sensitive patient-centered
      specific outcome evaluation after TBI.

PMID- 15986727
TI  - RNA editing: a molecular mechanism for the fine modulation of neuronal
      transmission.
AB  - The term "RNA editing" is used to identify any mechanism responsible for
      producing mRNA molecules with sequence information not specifically encoded in
      the DNA. RNA editing is therefore an important event in gene modification, which
      takes place at a post-transcriptional level. The molecular mechanism of RNA
      editing involves site-selective deamination of adenosine to inosine in pre-mRNA,
      which leads to altering translation codons and splicing in nuclear transcripts,
      whereby functionally distinct proteins can be produced from a single gene. The
      mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely
      expressed in brain and other tissues: however, up until now their substrates have
      mainly been found in the Central Nervous System (CNS). Of particular relevance in
      the CNS is the editing occurring at the ionotropic glutamate receptors (GluRs)
      level. Three AMPA and two Kainate receptors are subject to RNA editing. The
      consequence of this process is the substitution of specific amino acids in
      functionally critical positions of the receptors. Depending on the GluR involved,
      the consequences of editing will involve: activation and/or inhibition of
      splicing sites; modulation of the trafficking of the receptor to the plasma
      membrane; the process of tetramerization of the receptor subunits; modification
      of the ions passage through the receptor channel; modulation of the
      desensitization and action potential recovery times. All these events are
      specific to the different GluRs and are genetically and developmentally
      controlled. RNA editing is therefore a crucial event involved in controlling
      transmission of the action potential at the postsynaptic level. This modulation
      involves the transmission of all sensory stimuli to the CNS and gives rise to the
      "Sensotype". The Sensotype therefore defines the "way" in which the information
      acquired from the environment by the sensory systems is transmitted to the brain.
      The signals and inputs deriving from the Sensotype are transmitted to the brain,
      which processes and stores these signals thus generating the "Brainotype".
      Brainotype and Sensotype are genetically and environmentally determined; they are
      individually unique and specific to every living organism with a nervous system.
      Their characteristics are, at least in part, dependent on the modulation of the
      "RNA editing" process since glutamate receptors represent the main
      neurotransmitter system in the CNS.

PMID- 15986728
TI  - Inhibition of IkappaBalpha phosphorylation prevents glutamate-induced NF-kappaB
      activation and neuronal cell death.
AB  - NF-kappaB is a nuclear transcription factor involved in the control of
      fundamental cellular functions including regulation of cell survival. We
      investigated NF-kappaB activation induced by two opposing modulators of cell
      viability: IL-1beta and glutamate. We found that IL-1beta activated p50, p65 and
      c-Rel subunits of NF-kappaB, while glutamate activated only p50 and p65 proteins.
      Cell stimulation by glutamate, correlated with expression of the pro-apoptotic
      genes Caspase-3, Caspase-2L and Bax. Conversely, IL-1beta induced the expression
      of the short anti-apoptotic isoform of Caspase-2. Finally, we analysed the effect
      of the inhibition of IkappaBalpha degradation on glutamate-induced toxicity by
      using BAY 11-7082, a selective inhibitor of IkappaBalpha phosphorylation. Our
      results suggest that BAY 11-7082 preserves neuron viability from the glutamate
      mediated injury.

PMID- 15986729
TI  - Reorganization of cerebral circuits in human brain lesion.
AB  - Recovery after focal brain lesions is supposed to be mediated by cerebral
      reorganization. Stroke is a powerful model to study these processes in the human
      brain, since middle cerebral artery infarction is a common neurological disease
      with a clearly defined onset of a lateralized sensorimotor deficit syndrome.
      Brain tumours constitute a further model differing from stroke by their slow
      lesion dynamics. Evidence from functional neuroimaging and transcranial magnetic
      stimulation will be presented showing that recovery of hand function is related
      to reorganization of local perilesional and large-scale circuits involving the
      contralesional hemisphere.

PMID- 15986730
TI  - Transcranial magnetic stimulation in neurorehabilitation.
AB  - In neurorehabilitation, transcranial magnetic stimulation (TMS) offers
      information regarding prognosis and pathophysiology and could also be useful for
      therapeutic purposes. Numerous studies have indicated that, after stroke, the
      absence of motor evoked potentials is associated with a poor motor recovery. In
      contrast, MEPs obtained in the paretic muscle with low stimulus intensities
      suggest a good restitution of motor function. TMS studies have shown that the
      location of a brain lesion determines motor cortex excitability changes: Patients
      with central somatosensory lesions show a disinhibition in the ipsilesional motor
      cortex. Lesions in the territory of the superior cerebellar artery are associated
      with a loss of motor cortex excitability. Stroke patients participating in a
      Constraint-induced movement therapy show an enlargement of the motor output area
      in the affected hemisphere after therapy. This enhancement of motor excitability
      is associated with an improvement of motor function. Some evidence is emerging
      that the application of low frequency repetitive TMS over the non-lesioned
      hemisphere improves neglect phenomena by down-regulation of the excitability of
      the non-lesioned hemisphere.

PMID- 15986731
TI  - Is there impairment of a specific frontal lobe circuit in head injury?
AB  - There has been considerable interest in the role of anterior cingulate and
      lateral frontal cortex in normal cognition, and particularly its role in
      cognitive control. It has also been suggested that dysfunction of this frontal
      brain circuit is responsible for many of the cognitive deficits observed after
      head injury. Several recent PET and SPECT studies of head injury have lent
      support to this idea, and suggest that the hypothesis is worth further
      examination. The paper presents a selective overview of evidence that this
      specific frontal lobe circuit is impaired after head injury.

PMID- 15986732
TI  - Treating the aging brain: cortical reorganization and behavior.
AB  - Aging comprises many physiological modifications, including structural and
      metabolic changes, yet little is known about how aging affects the way in which
      neurons process and integrate sensory information from the environments. Here the
      framework of "modified use" as a determinant of cortical reorganization was
      applied for the investigation of age-related modifications of cortical maps and
      processing, and of associated changes of behavior. The age-related changes of
      walking behavior in rats were contrasted with the parallel changes of
      sensorimotor processing developing at the cortical level. Based on the regional
      specificity of these changes attempts are made to separate age-related changes
      arising as a consequence of degeneration from a result of adaptable processes
      following reduced use at high age. Finally, findings from long-term treatment
      with the Ca2+-blocker nimodipine, or from housing animals under enriched
      environmental conditions to ameliorate aging effects were described. Combined,
      these results show the general treatability of age-related changes. The data
      imply that age-related changes can be reversed by short periods of training and
      stimulation schedules even if they have developed. Clearly, the development of
      specific measures to delay aging processes and to rehabilitate aged brains
      depends on future progress in understanding mechanisms and effects of aging.

PMID- 15986733
TI  - The localization of central pattern generators for swallowing in humans--a
      clinical-anatomical study on patients with unilateral paresis of the vagal nerve,
      Avellis' syndrome, Wallenberg's syndrome, posterior fossa tumours and cerebellar
      hemorrhage.
AB  - BACKGROUND: Our understanding of brainstem swallowing centers is mainly based on
      experimental animals. In order to solve this problem also in humans, a clinical
      anatomical study on dysphagic patients with different lesion patterns was
      performed. PATIENTS AND METHODS: We studied 43 consecutively admitted dysphagic
      patients with unilateral paresis of the vagal nerve (PVN), Avellis' syndrome
      (AS), Wallenberg's syndrome (WS), posterior fossa tumour (PFT) or cerebellar
      hemorrhage (CH) with regard to clinical and anatomical aspects. FINDINGS: There
      was a continuum with regard to functional outcome from neurogenic dysphagia (ND):
      Patients with PFT or CH had a significantly worse outcome than patients with WS;
      the outcome of WS patients was significantly worse than that of patients with PVN
      or AS. In AS only the Nucleus ambiguus (NA) and its surrounding reticular
      formation (RF) were affected. In all patients with WS, the infarctions of the
      dorsolateral medulla were situated in the rostral third of the medulla and
      affected the NA and the Nucleus tractus solitarii (NTS) with their surrounding
      RF. In patients with PFT and CH, the NTS and its surrounding RF were affected on
      both sides. The overlap area of WS and PFT lesions is situated in the NTS and the
      surrounding RF, especially in its Nucleus parvocellularis. INTERPRETATION: Our
      results point to the fact, that in humans the dorsomedial central pattern
      generators (CPGs) for swallowing are situated in the rostral part of the dorsal
      medulla oblongata near the NTS/surrounding RF (especially Nucleus
      parvocellularis) and that the dorsomedial CPGs are superior to the ventrolateral
      CPGs (near the NA/surrounding RF) with regard to their swallowing-relevance.
      Furthermore, we hypothesize that due to the individual asymmetry of the
      swallowing-dominant forebrain hemisphere - the outcome from ND in WS depends on
      the side of the medullary infarction.

PMID- 15986734
TI  - Functional regeneration of the axotomized auditory nerve with combined
      neurotrophic and anti-inhibitory strategies.
AB  - Injury to the mammalian auditory nerve is associated with a lack of long-distance
      elongation and leads to definitive loss of the hearing function. To overcome this
      central nervous system typical lack of functional regeneration, a combined
      neurotrophic and antiinhibitory treatment is applied. After complete unilateral
      sectioning of the auditory nerve in adult rats a combination of the Nogo-A
      inhibitor IN-1 and the neurotrophic factor NT-3 is administrated intrathecally
      into the cerebellopontine angle for one week. Functional regeneration is
      evaluated by measuring auditory brainstem evoked potentials for a follow-up
      period of up to three months. After treatment, up to forty percent of the animals
      showed a second vertex-positive wave in the auditory brainstem evoked potentials
      which occurred between three to four weeks after sectioning and remained stable
      during the follow-up period. A limited degree of functional regeneration of the
      axotomized auditory nerve is possible after application of IN-1 and NT-3. For
      additional improvement of functional results further investigations on combined
      treatments with scar reducing agents, neurotrophic factors and neuroprotective
      drugs remain necessary.

PMID- 15986735
TI  - Electrically evoked hearing perception by functional neurostimulation of the
      central auditory system.
AB  - Perceptional benefits and potential risks of electrical stimulation of the
      central auditory system are constantly changing due to ongoing developments and
      technical modifications. Therefore, we would like to introduce current treatment
      protocols and strategies that might have an impact on functional results of
      auditory brainstem implants (ABI) in profoundly deaf patients. Patients with
      bilateral tumours as a result of neurofibromatosis type 2 with complete
      dysfunction of the eighth cranial nerves are the most frequent candidates for
      auditory brainstem implants. Worldwide, about 300 patients have already received
      an ABI through a translabyrinthine or suboccipital approach supported by
      multimodality electrophysiological monitoring. Patient selection is based on
      disease course, clinical signs, audiological, radiological and psycho-social
      criteria. The ABI provides the patients with access to auditory information such
      as environmental sound awareness together with distinct hearing cues in speech.
      In addition, this device markedly improves speech reception in combination with
      lip-reading. Nonetheless, there is only limited open-set speech understanding.
      Results of hearing function are correlated with electrode design, number of
      activated electrodes, speech processing strategies, duration of pre-existing
      deafness and extent of brainstem deformation. Functional neurostimulation of the
      central auditory system by a brainstem implant is a safe and beneficial
      procedure, which may considerably improve the quality of life in patients
      suffering from deafness due to bilateral retrocochlear lesions. The auditory
      outcome may be improved by a new generation of microelectrodes capable of
      penetrating the surface of the brainstem to access more directly the auditory
      neurons.

PMID- 15986736
TI  - Physiological recordings from electrodes implanted in the basal ganglia for deep
      brain stimulation in Parkinson's disease. the relevance of fast subthalamic
      rhythms.
AB  - Deep brain stimulation electrodes implanted in the subthalamic nucleus of
      patients with Parkinson's disease allow electrophysiological recordings from the
      human basal ganglia. Subthalamic local field potential recordings revealed the
      presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to
      surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly
      attractive because of their likely interaction with the excitatory mechanisms of
      action of deep brain stimulation. Here we investigated whether the two rhythms at
      70 Hz and at 300 Hz represent distinct modes of operation, and therefore
      different targets, within the subthalamic nucleus. We retrospectively analyzed
      the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain
      126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa
      administration. Whereas (as previously reported) 300 Hz activity was a consistent
      feature in the dataset, significant 70 Hz activity was observed in only 2 of 11
      nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the
      presence of 300 Hz oscillations. The two rhythms probably arise from different
      mechanisms, reflecting different functional and/or spatial aspects of subthalamic
      pathophysiology. Fast subthalamic oscillations could be exploited for intra
      operative electrophysiological monitoring of the subthalamic nucleus, post
      operative confirmation of electrode placement and patient-specific 'reglage' of
      the electrical parameters for chronic deep brain stimulation.

PMID- 15986737
TI  - DBS therapy for the vegetative state and minimally conscious state.
AB  - Twenty-one cases of a vegetative state (VS) and 5 cases of a minimally conscious
      state (MCS) caused by various kinds of brain damage were evaluated neurologically
      and electrophysiologically at 3 months after brain injury. These cases were
      treated by deep brain stimulation (DBS) therapy, and followed up for over 10
      years. The mesencephalic reticular formation was selected as a target in 2 cases
      of VS, and the CM-pf complex was selected as a target in the other 19 cases of VS
      and 5 cases of MCS. Eight of the 21 patients emerged from the VS, and became able
      to obey verbal commands. However, they remained in a bedridden state except for 1
      case. Four of the 5 MCS patients emerged from the bedridden state, and were able
      to enjoy their life in their own home. DBS therapy may be useful for allowing
      patients to emerge from the VS, if the candidates are selected according to
      appropriate neurophysiological criteria. Also, a special neurorehabilitation
      system may be necessary for emergence from the bedridden state in the treatment
      of VS patients. Further, DBS therapy is useful in MCS patients to achieve
      consistent discernible behavioral evidence of consciousness, and emergence from
      the bedridden state.

PMID- 15986738
TI  - Deep brain stimulation for idiopathic or secondary movement disorders.
AB  - Deep brain stimulation has gained increasing interest in the treatment of
      movement disorders. Presenting our clinical series of 179 patients operated upon
      since 1999, the indications, risks and benefits for the patients are discussed in
      order to further improve the techniques and their applications.

PMID- 15986739
TI  - Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and
      first results by the study group of the Italian neurosurgical society.
AB  - The preliminary results obtained by the Study Group for Treatment of Involuntary
      Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian
      Neurosurgical Society, are reported. The series includes 16 cases of very
      advanced Parkinson's Disease (PD), aged 46-81; 15 of them were not eligible for
      Deep Brain Stimulation. Ten cases have been evaluated at 3-30 months after
      implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2 8
      Volt, 100-400 microsec., 20-120 Hz) by chronically implanted electrodes,
      relieves, at least partially, but sometime dramatically, the whole spectrum of
      symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia
      are reduced. Standing, gait, motor performance, speech and swallowing are
      improved. Benefit is marked as far as axial symptoms is concerned. Also the
      symptoms of Long Term Dopa Syndrome -dyskinesias, motor fluctuations - and other
      secondary effect of levodopa administration psychiatric symptoms - are improved.
      Levodopa dosage may be reduced by 50%. The effect seems persistent and does not
      fade away with time. Improvement ranged, on the basis of the UPDRS scale, from
      <25% to 75%. There was only one case of complete failure. Quality of life is
      markedly improved in patients who were absolutely incapable of walking and unable
      arise out of chair. After stimulation they could walk, even if assistance was
      necessary. Improvement was observed also in those with disabling motor
      fluctuation and dyskinesias which could be abolished.

PMID- 15986740
TI  - Endocrine dysfunction following traumatic brain injury: mechanisms,
      pathophysiology and clinical correlations.
AB  - Despite growing recognition among those who provide care for traumatic brain
      injury patients, endocrine dysfunction following brain injury is an often under
      recognized phenomenon. From historical reports one would conclude that endocrine
      dysfunctions hardly ever occurs following trauma to the head. However, recent
      studies suggest that a significant proportion of patients suffer some degree of
      hypopituitarism. To date, there are no clear predicting factors identifying
      patients at risk for developing hormonal disturbances and thus no parameters
      exist for screening. Several retrospective analyses and literature reviews, and
      more recently, a few longitudinal studies of brain injured patients have been
      performed.

PMID- 15986741
TI  - Taylored implants for alloplastic cranioplasty--clinical and surgical
      considerations.
AB  - Traumatic loss of bone substance or post - decompression defects require the
      reconstruction of the skull. In cases of simple geometry there are handy, secure
      and cost effective procedures such as using autologuous cryopreserved bone flaps
      or polymerized Methylmethacrylat. For large sized defects CAD - taylored implants
      developed to provide a comfortable procedure to ensure high biocompatibility and
      perfect anatomical results by one - stage surgery. Furthermore cranioplasty does
      not only imply anatomical reconstruction but also functional recovery of
      awareness, cognition and motoric functions as shown in several studies according
      to changes in cerebral hemodynamics and metabolism. In our series of 286 patients
      who underwent cranioplasty during the past 10 years (1993-2003) we used taylored
      implants in 15 cases starting in 1999. All the patients included showed large
      sized defects > 64 cm2, complications did not occur neither during surgery nor
      the postoperative course, cosmetical results were excellent in all the patients.
      Neurological findings and the functional state improved in 11/15 patients, 4/15
      patients showed no change, nevertheless these patients had reached a good
      recovery before surgery. Application of this technique is limited by cost,
      nonetheless it is recommended for extensive reconstruction of the skull.

PMID- 15986742
TI  - Lessons from national and international TBI societies and funds like NBIRTT.
AB  - While Neurotrauma is a growing public health problem worldwide, governments have
      not been able to respond to the silent epidemic of brain injury. Neurotrauma,
      according to the World Health Organization, will surpass many diseases as the
      major cause of death and disability by the year 2020. Not-for-profit
      organizations, professional societies and foundations have begun to address the
      problem of Neurotrauma through educational conferences, training seminars,
      prevention activities, passage of laws and regulations, and by providing grant
      funding. Private sector partnerships with government entities appear to be a
      significant means of addressing a major public health problem.

PMID- 15986743
TI  - Brachial plexus surgery (honorary lecture).
AB  - Brachial plexus injuries (B.p.i.) are lesions occurring more and more frequently
      due to high velocity road and sport traumas. They are severe lesions with
      disabling sequelae. Surgical procedures and results could greatly be improved in
      the last 2 decades. Although the anatomy of brachial plexus is well known, less
      known are the functional maps of the various brachial plexus elements. In this
      paper treatment modalities for obstetrical, traumatic (adult) and actinic B.p.i.
      are being described too.

PMID- 15986745
TI  - Macrophages and dendritic cells treatment of spinal cord injury: from the bench
      to the clinic.
AB  - The failure of the spinal cord to recover after injury has been associated with
      the immune privilege mechanism that suppresses immune activity throughout the
      central nervous system. Primed macrophages and dendritic cells were shown to
      promote neurological recovery in preclinical models of spinal cord injury. A cell
      therapy consisting of autologous incubated macrophages is now being tested on
      spinal cord injury patients in clinical trials.

PMID- 15986744
TI  - Results in brachial plexus palsy after biceps neuro-muscular neurotization
      associated with neuro-neural neurotization and teno-muscular transfer.
AB  - None of the currently used techniques for elbow flexion recovery in brachial
      plexus recovery offers enough strength for normal life activities. The
      association between several methods grants a better result by a summarizing
      effect compared to each method used separately. The paper reveals the improvement
      of the functional results in brachial plexus reconstruction by combining the
      techniques of nerve repair (nerve grafts, nerve transfers or direct muscular
      neurotization) with palliative muscular transfers. Of the 54 cases of
      microsurgical reconstruction of brachial plexus palsy, in 20 cases we associated
      a muscular transposition: 7 latissimus dorsi transfers (5 monopolar and 2
      bipolar), 5 pectoralis major and 8 triceps transfers. The direct neuro-muscular
      neurotization of the biceps-EMG efficient - was associated with a muscular
      transfer in 8 cases: in 4 of the 7 latissimus dorsi transfers, in 3 cases of
      triceps transfer and in 2 case of pectoralis major transfer. The association of
      the 3 methods - direct neuromuscular neurotization, neuro-neuronal neurotization
      and muscular transfer - has a summarizing effect in the flexion restoration of
      the elbow flexion, which represents a major problem in the brachial plexus palsy.

PMID- 15986746
TI  - Electrophysiological effects of 4-aminopyridine on fictive locomotor activity of
      the rat spinal cord in vitro.
AB  - Recently the K+ channel blocker 4-aminopyridine (4-AP) has been suggested to be
      useful to improve motor deficits due to spinal cord lesions. There is, however,
      little basic research support for this action of 4-AP. In this study we have used
      as a model the neonatal mammalian spinal cord in vitro that generates a rhythmic
      activity termed fictive locomotion (induced by bath-application of NMDA + 5-HT)
      with phasic electrical discharges alternating between flexor and extensor motor
      pools and between left and right motoneurons within the same segment. When 4-AP
      was added in the presence of sub-threshold concentrations of NMDA + 5-HT, there
      was facilitation of fictive locomotion which appeared with alternating patterns
      on all recorded ventral roots (VR). Furthermore, in the presence of 4-AP, weak
      dorsal root (DR) stimuli, previously insufficient to activate locomotor patterns,
      generated alternating discharges from various VRs. The present data show that 4
      AP could strongly facilitate the locomotor program initiated by neurochemicals or
      electrical stimuli, indicating that the spinal locomotor network is a very
      sensitive target for the action of 4-AP.

PMID- 15986747
TI  - Alternative, complementary, energy-based medicine for spinal cord injury.
AB  - This paper provides an overview on various alternative, complementary, or energy
      based therapies that expand the healing spectrum of individuals with spinal cord
      injury (SCI). Not only do they have the capability to help a variety of secondary
      conditions, they have the ability in some people, for certain injuries, to
      restore function, sometimes dramatically. After providing an overall contextual
      rationale for the use of alternative medicine, this paper briefly summarizes
      various Eastern-medicine healing modalities, laser-based therapies, nutritional
      and homeopathic approaches, and pulsed electromagnetic therapies.

PMID- 15986748
TI  - The effect of penile vibratory stimulation on male fertility potential,
      spasticity and neurogenic detrusor overactivity in spinal cord lesioned
      individuals.
AB  - PURPOSE: Present the possibility for treatment of male infertility, spasticity,
      and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals
      with penile vibratory stimulation (PVS). METHOD: Obtaining reflex-ejaculation by
      PVS, by using a vibrator developed for this purpose. The stimulation was
      performed with a vibrating disc of hard plastic placed against the frenulum of
      the penis (amplitude > or = 2.5 mm). The vibration continued until antegrade
      ejaculation or for a maximum of 3 minutes followed by a pause of 1 minute before
      the cycle was repeated, maximally 4 times. RESULTS: >80% SCL men are able to
      obtain ejaculation with PVS. Pregnancy rates obtained with home PVS and intra
      vaginal insemination was 22-62% (4 studies), and with PVS or electroejaculation
      and intrauterine insemination/in-vitro fertilization/intracytoplasmatic sperm
      injection 39-64% (9 studies). PVS was demonstrated to decrease spasticity
      significantly when measured by the modified Ashworth scale. In addition, a
      decrease of the number of spontaneous EMG events which probably indicate spasms
      was observed. Increase in bladder capacity at leakpoint following 4 weeks of
      frequent ejaculation with PVS treatment was likewise demonstrated. CONCLUSION:
      PVS has proved its importance for SCL male fertility, in the years to come its
      place in treatment of spasticity and neurogenic detrusor overactivity has to be
      established.

PMID- 15986749
TI  - Posttraumatic syringomyelia--a serious complication in tetra- and paraplegic
      patients.
AB  - Post-traumatic syringomyelia (PTS) is relatively rare, but its complications can
      be serious. In the beginning of the operative treatment (1900-1930), scarring
      could be reduced to a certain degree. In modern treatment (1980 1990) a shunt
      implantation showed also little effect in long-term follow-up studies. Influenced
      by the work of B. Williams, 58 PTS patients underwent surgery to create a
      pseudomeningomyelocele, an artificial CSF reservoir, performed to normalize the
      CSF flow. In a 10-year-postoperative follow-up study (minimum observation two
      years), good results were obtained in more than 70%.

PMID- 15986750
TI  - Functional neurorehabilitation in locked-in syndrome following C0-C1
      decompression.
AB  - Today, thanks to intensive care treatment and modern diagnostic tools,
      increasingly more patients with severe brain and spinal cord lesions, mainly
      secondary to accidents, stroke, tumours, and congenital malformations survive the
      acute impact on the central nervous system (CNS). Complicated operative
      procedures and concomitant complication may also lead to severe impairment of the
      sensory motor and cognitive behavioural functioning as it can be described
      according to the WHO-ICF criteria. New developments of functional
      neurorehabilitation in neurosurgery can significantly improve patients' quality
      of life (QoL) in terms of both brain and body functioning and certain health
      related components of well-being (such as social activities and leisure).
      Rehabilitation starts with assessment of the functional impairment and the
      underlying pathophysiology by using all modern diagnostic tools. Our concept of
      postoperative neurorehabilitation is exemplarily demonstrated in one patient who
      suffered from acute postoperative locked-in syndrome. Surgical decompression and
      fusion were required for post traumatic and recurrent congenital craniovertebral
      instability at C0-C1. Subsequent functional neurorehabilitation is based on
      careful planning in accordance with our concept of a holistic Spectrum of
      functional early Neurorehabilitation.

PMID- 15986751
TI  - Treatment options and results in cervical myelopathy.
AB  - Cervical myelopathy is a clinical entity resulting from external compression of
      the cervical medulla. The clinical course can be divided into the acute form
      (secondary to trauma) versus subacute (progression within weeks to months) and
      chronic cervical myelopathy (months to years). The clinical picture of myelopathy
      is that of unsteady gait with long-tract signs, such as hyperreflexia, spasticity
      and extensor plantar responses. Between 1997 and 2000, 359 consecutive patients
      have been operated on in our department presenting with a variety of symptoms
      related to compression of the cervical medulla. Beside of standard MRI for all
      patients we applied SSEPs, gait analysis and dynamic MRI studies as additional
      helpful tools in evaluating selected patients pre- and postoperatively. We prefer
      the anterior approach as first-line approach because in the majority of patients
      the osteophytic spurs are more dominant anteriorly, and after anterior
      decompression and stabilization the posterior approach appears safer. We also
      favor the more extended approach of spondylectomy versus multilevel decompression
      in patients with bisegmental or multisegmental spinal canal stenosis. However it
      seems to be that radicular decompression is better achieved through multilevel
      decompression than through spondylectomy.

PMID- 15986752
TI  - The treatment of the sacral pressure sores in patients with spinal lesions.
AB  - Sacral pressure sore treatment requires a multidisciplinary approach, the
      surgical procedures following nutritional and medical status rehabilitation,
      spasticity control and sepsis treatment. Serial surgical debridement might also
      precede flap coverage. Gluteal flaps design such as rotation, transposition or V
      Y advancement is selected according to the shape and size of the sore. Our
      experience with 74 patients with 95 flaps includes 38 rotation flaps, 28 V-Y and
      8 transposition flaps. Twenty one patients had bilateral gluteal V-Y flaps. Only
      2 transposition flaps had marginal necrosis that healed per secundam. Delayed
      healing occurred in 12 cases due to sepsis, that healed spontaneously in 10 cases
      and required surgical reintervention for excision and flap reposition in 2.
      Prolonged bed immobilization, postoperative antibiotic therapy and late suture
      removal are important factors in surgical success.

PMID- 15986753
TI  - Phenomenological aspects of consciousness--its disturbance in acute and chronic
      stages.
AB  - The meaning of a disturbance of consciousness is completely different in an acute
      as opposed to a chronic stage. In the acute stage, the grade of arousal is the
      most essential component in order to assess the changes of the level of
      intracranial pressure in neurosurgical emergency room. A new coma scale called
      Emergency Coma Scale has been proposed, which represents a combination of the
      Glasgow Coma Scale and the Japan Coma Scale. In the chronic stage, however,
      contents of consciousness or mental function deserve phenomenological and
      holistic investigations, keeping the difference between consciousness and mind in
      consideration, in order not only to treat and care for patients following
      cerebral injuries, stroke and mild cognitive impairment in aged people. We
      propose the difference in conception between consciousness and mind; that is,
      consciousness consists of psycho-sensory afferent system, mind of psycho-motor
      efferent and afferent system, and memory and language as liaison officers between
      them. This proposal would play a role to understand mental change in the natural
      aging processes, when memory and cognition are deteriorating gradually, but is
      still in evolution in the field of culture.

PMID- 15986754
TI  - Neuropsychological experiences in neurotraumatology.
AB  - My work in Neurotraumatology was initiated in 1961, when I as a neuropsychologist
      got a position in a neurosurgical University department. The tasks were to
      evaluate the mental state of patients, give advices to family members regarding
      the mental and social prognosis of the patients and to support nurses in the
      initial care of the patients. Initially the methods that were made use of were
      tests developed by the German neurologist Kurt Goldstein and traditional
      psychometric tests, but it was not until the theories of A. R. Luria and his
      investigation method were applied that a true position as a member of the
      treatment team was secured. Reading Luria's book "Higher Cortical Functions in
      Man" made me aware of his theories. The skill to perform the investigation was
      acquired during visits to Luria's laboratory at the Bourdenko Neurosurgical
      Institute in Moscow in the nineteen-seventies. Text and material to "Luria's
      Neuropsychological Investigation" was published in 1974. The early work was
      further stimulated by the development in the neurosciences regarding brain
      plasticity and brain repair and experiences from visits to rehabilitation centres
      in the US, Yehuda Ben-Yishay's center at New York Medical School, George
      Prigatano's centre at the time in Oklahoma, and Lance Trexler's center at
      Community Hospital, Indianapolis led in 1985 to the establishment of the first
      post acute rehabilitation center in Europe: the Center for Rehabilitation of
      Brain Injury (CRBI) at the University of Copenhagen, DK. The main program was a
      holistic day program, six hours a day for four months in accordance with the
      university semesters, and an eigth months follow-up. Groups of 15 persons started
      together, collaborating in smaller groups. The present director of the CRBI is
      neuropsychologist Frank Humle. A thorough follow-up of the patients' state and
      improvement through the course of treatment towards social integration, including
      getting back to work was performed, and studies have indicated that successful
      integration of the traumatized patient is possible, provided that an early
      intensive care is succeeded by a comprehensive, individualized post-acute
      rehabilitation program, of which follow-up is a part, all within the frame of
      multidisciplinary collaboration.

PMID- 15986755
TI  - Team care in ICU--psychotherapeutic aspects and taking care of family of patients
      with traumatic brain injury.

PMID- 15986757
TI  - Predicting one year clinical outcome in traumatic brain injury (TBI) at the
      beginning of rehabilitation.
AB  - Predicting long-term clinical outcome for patients with traumatic brain injury
      (TBI) at the beginning of rehabilitation provides essential information for
      counseling of the family and priority-setting for the limited resources in
      intensive rehabilitation. The objective of this study is to work out the
      probability of the one-year outcome at the beginning of rehabilitation. Sixty
      eight patients with moderate-to-severe TBI and known one-year outcome were
      employed for outcome prediction using the logistic regression model. A large
      number of prospectively collected data at admission (age, Glasgow Coma Scale
      [GCS] Score, papillary response), during intensive care unit (ICU) management
      (duration of coma, intracranial pressure [ICP] and its progress) and at the
      beginning of rehabilitation (baseline Functional Independence Measure [FIM],
      Neuro-behavioral Cognitive Status Examination [NCSE] and Functional Movement
      Assessment [FMA]) were available for preliminary screening by univariate
      analysis. Six prognostic factors (age, GCS, duration of coma, baseline FIM, NCSC
      and FMA) were utilized for the final logistic regression model. Age, GCS and
      baseline FIM at the beginning of rehabilitation have been found to be independent
      predictors for one-year outcome. The accuracy of prediction for a good Glasgow
      Outcome Score is 68% and an outcome for disability (either moderate or severe) is
      83%. Validation of this model using a new set of data is required.

PMID- 15986756
TI  - Early clinical predictive factors during coma recovery.
AB  - In severe brain injury patients few studies have examined the role of early
      clinical factors emerging before recovery of consciousness. Patients suffering
      from vegetative state and minimally conscious state in fact may need variable
      periods of time for recovery of the ability to follow commands. In a previous
      study we retrospectively examined a population of very severe traumatic brain
      injury patients with coma duration of at least 15 days (prolonged coma), and we
      found, as significant predictive factors for the final outcome, the time interval
      from brain injury to the recovery of the following clinical variables: optical
      fixation, spontaneous motor activity and first safe oral feeding. Psychomotor
      agitation and bulimia during coma recovery were also favourable prognostic
      factors for the final outcome. In a further study, also as for the
      neuropsychological recovery, the clinical variable with the best significant
      predictive value was the interval from head trauma to the recovery of safe oral
      feeding. In the present study the presence of psychomotor agitation diagnosed by
      means of LCF (score 4 = confused-agitated) at the admission time in
      rehabilitation predicted a statistically significant better outcome at the
      discharge time in comparison with patients without agitation.

PMID- 15986758
TI  - Severe brain injuries in children.
AB  - Authors present a seven years retrospective study on 85 cases of severe brain
      injuries (SBI) in children (GCS </= 8) treated in the Pediatric and ICU
      Departments of the Clinic Hospital "Bagdasar-Arseni" Bucharest, Romania. The
      relationship between ICP, GCS on admission, the CT-scan/MRI alteration and the
      outcome evaluated by the Glasgow Outcome Scale (GOS) were studied in order to
      highlight the most important factors to improve prognosis. An overall mortality
      of 25.9% was found in this series. Authors concluded that the ICP values at
      admission >/= 20 mmHg, the Diffuse Axonal Injury (DAI) on MRI and the GCS on
      admission are factors of prognosis in SBI in children. The politrauma context is
      an aggravating factor for SBI in this age group. Other factors which influence
      GCS on admission may have prognostic importance i.e.: prehospital care, transport
      time and adequate transport conditions.

PMID- 15986759
TI  - The locked-in syndrome: a challenge for therapy.
AB  - The locked-in syndrome (LIS) is a severe condition originated by a ventral pons
      lesion causing quadriplegia and anarthria but with a preserved consciousness. LIS
      seems to be a well defined clinical picture, although different problems still
      persist, such as the diagnosis as it is usually mistaken for akinetic mutism and
      a vegetative state; the unclear prognosis, because of the patient's psychological
      state and the lack of information and data concerning the different types of
      available treatment and the need for results. Rehabilitation is a challenge for
      physicians, new methods and techniques of specialized treatments for these
      patients are opening a new future that will allow us to abandon the initial
      pessimism. A more efficient rehabilitation of these patients depends on the
      intensity of the rehabilitation, the multidisciplinary approach, and duration of
      the treatment.

PMID- 15986760
TI  - WFNS committee for neurorehabilitation.

PMID- 15986761
TI  - Academia Multidisciplinaria Neurotraumatologica AMN.

PMID- 15986762
TI  - [Hormone risk factors during breast tumoral promotion, progression and
      prognosis].
AB  - BACKGROUND: Several hormonal factors, as menstrual irregularities, early ovarian
      maturation and long estrogen stimulation during women's reproductive life, have
      been pointed out as risk factors in the breast cancer promotion. OBJECTIVE: To
      study the various involved factors during breast cancer evolution. MATERIAL AND
      METHODS: Hormonal and reproductive factors were studied in 200 women with breast
      cancer. The greater incidence was showed in postmenopausal patients (118
      patients). RESULTS: Nulliparity was presented in 29% of the patients, while late
      menopause and early menarche were presented in 25 and 8%, respectively. Having
      the first child at age > 30 years and family history of breast cancer (8.5%) were
      risk factors presented in 40% of the patients. Thirty percent of the patients
      showed low risk factors such as: high parity (26%), low parity (15%) and first
      child at age < 20 years. On the other hand, the left mammary gland was the most
      affected. The lesion was mainly situated in the upper-outer quadrant and upper
      inside quadrant (36 and 26% in 72 and 52 patients, respectively). The decade of
      highest incidence was 40 to 50 years. During the first six months, 60% of the
      patients showed tumour progression. CONCLUSION: Nulliparity, late menopause,
      early menarche, first child at age > 30 years and family history of breast cancer
      are risk factors for serious breast cancer prognostic.

PMID- 15986763
TI  - [Plasma and milk concentrations of acenocoumarin in breast-feeding women during
      post partum].
AB  - BACKGROUND: Patients are receiving anticoagulants during postpartum. Literature
      data still is controversy in milk excretion of acenocoumarin; there are conducts
      in favor and against. Because of the benefits of maternal milk it's necessary to
      probe if acenocoumarin is excreted by human milk. OBJECTIVE: To determine the
      milk excretion of acenocoumarin in different periods of the postpartum and the
      milk excretion index in anticoagulant women. MATERIAL AND METHODS: It's an
      observational, descriptive and prospective study. The milk and plasma
      concentrations of acenocoumarin were determined in breast-feeding mothers with
      anticoagulation during the postpartum. ANOVA was used to determine the
      differences in pharmacokinetic constants in the different days of study. RESULTS:
      Two patients required light anticoagulation, nine moderate and five intense. The
      37.5% of the new born were full term hypotrophy and the 18.75% were preterm. The
      highest plasma average concentration of acenocoumarin was found in day 45th
      postpartum (0.21 microg/mL). Acenocoumarin present in milk was found until day
      30th; the average concentrations were low 0.011 microg/mL. The value of the
      maternal milk excretion index was 0.057 in day 45, what represents that
      approximately the 5% of acenocoumarin is eliminated by milk. The calculated dose
      of acenocoumarin that a new born could receive through maternal milk was lower
      than the recommended doses (1.79 microg/kg/day). CONCLUSION: These results
      allowed us to recommend breastfeeding in patients who are been anticoagulated
      with acenocoumarin.

PMID- 15986764
TI  - [Relation among pathological maternal history and weight diagnosis at birth].
AB  - BACKGROUND: Maternal age over 35 and lower than 18 years, primiparity, certain
      disorders such as blood pressure, diabetes mellitus and infections have been
      related to weight disorders of the newborn. OBJECTIVE: To asses risks of
      occurrence of two birth weight diagnostic criteria: 1) low birth weight and
      macrosomia; 2) trophism adjusted for gestational age, considering several
      maternal pathologies. MATERIAL AND METHODS: A cross-sectional study of 316
      newborns, singletons and free of malformations or congenital infections was
      carried out. We calculated risk of low birth weight, macrosomia, hypotrophy and
      hypertrophy according to the presence of the following maternal pathologies:
      hypertension, diabetes mellitus, infections, and other disorders. We also
      determined sensitivity and specificity indexes to asses the validity of the low
      birth weight and macrosomia criteria. RESULTS: For low birth weight and
      macrosomia we found a sensitivity of 91.7% and 53.3%, and a specificity of 86.19%
      and 100%, respectively. The presence of maternal hypertension and diabetes
      mellitus were risk factors for low birth weight (OR = 2.426; CI95% = 1.210-4.900)
      and macrosomia (OR = 5.143; CI95% = 1.520-17.420), respectively; these risks were
      not significant when the trophism criterion was used. CONCLUSIONS: The low birth
      weight and macrosomia criteria over and underestimated criteria for hypotrophy
      and hypertrophy. According to the presence of maternal hypertension and diabetes
      mellitus, the risk of low birth weight and macrosomia are overestimated in
      relation to those seen when the trophism criterion was used.

PMID- 15986765
TI  - [Hypocalciuria during pregnancy as a risk factor of preeclampsia].
AB  - BACKGROUND: Although preeclampsia has been studied thoroughly, its origin is
      still unknown. However, there are various factors that strive to explain its
      cause. Some of them are: the genetic, placenta and immunological aspects,
      endothelial damage, hormonal and autoimmunological alterations, deficit of
      essential fatty acids, and the ion disorder theory. OBJECTIVE: To evaluate if
      hypocalciuria is a factor related to the development of preeclampsia or
      transitory hypertension during pregnancy. MATERIAL AND METHOD: A cohort study of
      63 women was performed. Serum calcium levels and calcium in 24 hours urine
      collection were assessed in women with 32 to 36 weeks of pregnancy. Patients were
      selected by sampling of consecutive cases. RESULTS: Twenty-four patients had
      hypocalciuria (group I) and 39 normocalciuria (group II). Calcium serum levels
      were of 8.05 +/- 0.22 mg/ dL and of 8.22 +/- 0.36 for group I and II,
      respectively (t=1.25, p=0.21). Of the 24 patients with hypocalciuria, 5 (20.83%)
      had preeclampsia compared to 2 (5.12%) of the 39 with normocalciuria (RR= 4.06;
      95% CI 3.29, 7.20). We did not find correlation between preeclampsia and the risk
      factors. When considering hypocalciuria as a prognosis test, we obtained 0.71 of
      sensitivity and 0.66 of specificity; the exactitude of the test was of 0.66.
      CONCLUSIONS: Hypocalciuria could be considered as a risk factor for the
      development of preeclampsia and transitory hypertension during pregnancy.

PMID- 15986766
TI  - [Assessment of efficacy of ketoconazole/clindamycin vs metronidazole/nistatine in
      candidiasic vaginitis and bacterial vaginosis].
AB  - BACKGROUND: Term vaginitis refers to vaginal mucosa's inflammation, which
      produces a great variety of symptoms, including: abundant genital draining, of
      different color, fetid odor, pruritus, irritation, heat, dyspareunia, underwear
      spotting and frequently it is related to heat when urinating. OBJECTIVE: To
      compare the ketoconazole/klindamycin vs metronidazole/nistatine efficacy for the
      treatment of vaginitis. MATERIAL AND METHODS: Efficacy of the
      ketoconazole/klindamycin vs metronidazole/nistatine combination to treat Candida
      vaginitis and bacterial vaginosis by vaginal route was compared. Patients with
      diagnosis of vaginitis and bacterial vaginosis were included in a longitudinal,
      prospective, double-blind study. Patients were treated with
      ketoconazole/clindamycin vaginal tablets or metronidazole/ nistatine ovules for 6
      days. Patients were evaluated at baseline and at day 7. RESULTS: The global
      result showed that ketoconazole/clindamycin is superior to
      metronidazole/nistatine in the treatment of vaginitis/ vaginosis. C. albicans was
      isolated in 23 patients, 12 in the ketoconazole/clindamycin group and 11 in the
      metronidazole/nistatine group. At the end of the study, cultures were negative in
      66.7% of ketoconazole/clindamycin group and in 54.5% of metronidazole/nistatine
      group. Eighteen cases presented mixed vaginitis, 13 in ketoconazole/clindamycin
      group and 5 in metronidazole/nistatine. At the end of the study, culture was
      negative in ketoconazole/clindamycin (83.3%) group and in all
      metronidazole/nistatine cases. Anaerobes were isolated in 21 patients, 9 in
      ketoconazole/clindamycin group and 12 in metronidazole/nistatine. At the end of
      the treatment, cultures were negative in 77% of ketoconazole/clindamycin group
      and in 66% of metronidazole/nistatine group; adverse reactions were not reported.
      CONCLUSION: Treatment with ketoconazole/clindamycin for vaginitis/vaginosis is
      similar to that of metronidazole/nistatine. Microbiologically and clinically,
      treatment was well tolerated since there were not adverse reactions during the
      course of it.

PMID- 15986767
TI  - [Effect of vasectomy on arginase's activity in accessory sexual glands of rats].
AB  - BACKGROUND: Although vasectomy is the most used contraceptive method, its effect
      over male biochemical and physiological parameters has not been evaluated.
      OBJECTIVE: To study the effect of vasectomy on arginase activity in accessory sex
      glands of the rat. MATERIAL AND METHODS: Twenty male healthy rats weighing 300
      350 g were divided into four groups (n = 5). Groups I, II and III were
      vasectomized, and group IV was the control group. In order to measure the
      activity of arginase in the accessory sex glands, glucose, triglycerides and
      protein concentration, as well as arginase activity in serum, rats were killed at
      4, 30 and 60 days post-surgery. RESULTS: The biochemical parameters of serum
      changed following vasectomy, but it is possible that these changes were at
      random. However, arginase activity in serum in accessory sex glands was not
      affected by vasectomy. CONCLUSION: Vasectomy does not affect arginase activity in
      accessory sex glands of male rats in spite of the high activity observed in short
      time in both coagulant and bulbourethral glands. Changes observed in serum
      biochemical parameters, which included glucose, triglycerides, proteins, arginase
      and alkaline phosphatase activities, were not relevant.

PMID- 15986768
TI  - [Uterosalpingography].

PMID- 15986769
TI  - The historical development of occupational health in Australia Part 2: 1970-2000.
AB  - Australian occupational health was shaped by various social, political and
      economic forces during the latter half of the last century. An overall downturn
      in manufacturing and increased wage restraint during the early 1970s, encouraged
      trade unions to turn their attention to broader social issues, such as workplace
      health. Mainstream Australian society was also being influenced by wider
      community sentiment during this time, including anti-war protests, environmental
      lobby groups and the women's movement. Interest in occupational health
      subsequently flourished, with formalised education commencing in the 1970s, and
      the number of tertiary courses rapidly increasing throughout the 1980s.
      Occupational health and worker's compensation legislation similarly evolved
      throughout the latter stages of the twentieth century. Australian workplace
      health and safety is now based on a theory of self-regulation and managed in a
      tri-partite model, consisting of employers, trade unions and government
      departments. In Part 1 of our occupational health review, we outlined the
      historical development of Australian occupational health between 1788 and 1970.
      In the current paper, Part 2, we describe the historical development of
      Australian occupational health between 1970 and 2000.

PMID- 15986770
TI  - Simultaneous analysis of termiticides in indoor air by using gas chromatography
      mass spectrometry.
AB  - We have established a method for simultaneously analyzing termiticides (13 kinds)
      in indoor air based on collection by combination of quartz filter and C18 Empore
      extraction disks, and measurement using gas chromatography mass spectrometry
      (GC/MS). The lower limit of determination for each substance was 0.02 microg/m3
      when 2 m3 of air was sampled. The recovery was 66-100%, and the relative standard
      deviation was 3.7-14.2%. In experiments using a model box with commercial
      termiticides, we verified that emissions of bis (2, 3, 3, 3-tetrachloropropyl)
      ether (S421) increased with a rise in temperature from 10 degrees C to 20 degrees
      C to 40 degrees C, whereas almost no etofenprox was released into the air
      regardless of temperature. In addition, decanal, nonanal and alkanes (C13 and
      C14), which are major components of termiticides, were detected in relatively
      high concentrations. In the present study, regardless of low vapor pressure of
      the termiticides, several compounds were detected with the model box experiment.
      The conclusion that can be drawn is that it is necessary to survey the indoor
      environmental pollution.

PMID- 15986771
TI  - Modulation of Na(+)-dependent glutamate transporter of murine astrocytes by
      inflammatory mediators.
AB  - Sodium-dependent glutamate transporters of astrocytes have been reported to
      maintain extracellular concentration of glutamate below toxic level in the
      central nervous system and to be concerned with neurodegenerative disorders,
      including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). In
      this study, the effects of inflammatory mediators including prostaglandin (PG)
      E2, interleukin (IL)-1beta and IL-6 on Na(+)-dependent L-glutamate transport of
      astrocytes were analyzed using primary murine astrocytes. The exposure of
      astrocytes to PGE2 for 24 h elicited a dose-dependent increase of L-glutamate
      uptake. Neither IL-beta nor IL-6 alone had any effect on L-glutamate uptake.
      However, IL-1beta enhanced the PGE2-induced increase of L-glutamate uptake. IL-6
      suppressed the increase of L-glutamate uptake induced by PGE2. Kinetic analysis
      of L-glutamate uptake showed that PGE2 and PGE2 with IL-1beta increased V(max)
      value with no significant effect on Km value for Na(+)-dependent L-glutamate
      uptake. IL-6 suppressed the PGE2-induced V(max) value. These results suggest that
      IL-1beta, IL-6 and PGE2 modulate glutamate transport of astrocytes and play a
      role in the pathogenesis of neurodegenerative disorders such as ALS and AD.

PMID- 15986772
TI  - Life satisfaction and functional disabilities in long-term survivors after first
      stroke.
AB  - Despite good recovery from a stroke, the quality of life (QOL) of most stroke
      patients living in the community is not always restored in their acute or
      recovery phase. Our aim of this study was to evaluate the relation between
      basic/social functional disabilities and life satisfaction (one of the indicators
      of QOL) in long-term survivors after a first stroke. Sixty three consecutive
      outpatients who had received comprehensive inpatient rehabilitation after their
      first stroke participated in this cross-sectional study. The profile, basic
      activities of daily living, life style and life satisfaction of these outpatients
      were evaluated based on their interview. More than half of the subjects had a
      decrease in life satisfaction. There was mostly weak positive correlation between
      functional/social disabilities and the life satisfaction, and both age and sex
      were not predictors of their QOL. Therefore, functional disabilities had a weak
      impact on QOL in the long-term survivors after the first stroke.

PMID- 15986773
TI  - Indication for nateglinide in type 2 diabetes mellitus.
AB  - Nateglinide is a novel rapid- and short-acting insulin secretagogue that
      ameliorates postprandial hyperglycemia by improving insulin secretory dynamics to
      a near normal level more effectively than sulfonylureas. Recent epidemiological
      studies have demonstrated that postprandial hyperglycemia can result in
      arteriosclerosis, and that advanced arteriosclerosis is present in the initial
      stage of impaired glucose tolerance. Since postprandial hyperglycemia could be
      well treated by nateglinide, we examined the background factors of type 2
      diabetic patients to determine the optimal indication for nateglinide. Our
      results indicate that nateglinide is most effective in young and obese patients.
      Furthermore, fewer responders had microangiopathy or were previously on oral
      hypoglycemic agents or sulfonylureas compared with non-responders. Although
      nateglinide is generally indicated for patients with mild HbA1c level, the
      present findings indicate that the drug was effective in the aforementioned
      patients regardless of pretreatment HbA1c levels. In one obese patient,
      nateglinide improved late hyperinsulinemia to near normal secretory dynamics. Our
      findings suggest that nateglinide is a physiologically preferable and useful drug
      for early type 2 diabetes without microangiopathy.

PMID- 15986774
TI  - Prolonged survival in a female with untreated tetralogy of Fallot.
AB  - It has been reported that most patients with untreated tetralogy of Fallot (TOF)
      die by the time they reach adulthood. We report the case of a 72-year-old female
      diagnosed by echocardiography and cardiac cathetherization as having TOF and
      diagnosed at birth with a ventricular septal defect (VSD). During childhood, she
      was very thin and lacking in physical strength. On first consultation at our
      hospital, she was suffering from mild dyspnea, classified as NYHA functional
      class III, and her fingers were clubbed and cyanotic. Her PaO2 was 48.0 mmHg
      under room air, and hypoxia was recognized. An echocardiography and cardiac
      cathetherization showed a VSD, hypertrophy of the right ventricle, over-riding of
      the aorta and stenosis of the right ventricular outflow tract with a pressure
      gradient of 84 mmHg. There was a bidirectional shunt with 24% flow from the left
      to right and 43% from the right to left ventricle. Her Qp/Qs was 0.75. Surgical
      treatment was recommended. However, the patient refused, because her symptoms
      were alleviated with home oxygen therapy. This report shows the prolonged
      survival of this 72-year-old female with untreated TOF.

PMID- 15986775
TI  - Applying a solution-focused approach to support a worker who is under stress.
AB  - The solution-focused approach (SFA) developed by Insoo Kim Berg and Steve de
      Shazer at the Brief Family Therapy Center, Milwaukee, USA is classified as brief
      psychotherapy. We believe that SFA can give an occupational healthcare staff
      useful tools that will positively influence their relationships with workers,
      because it focuses on workers' strengths rather than their weaknesses when the
      staff interviews them using SFA. In this report, we explain the case of a worker
      who was under stress and was interviewed using SFA. Although the worker came to
      the interview because of his physical symptoms, he disclosed that he was under
      considerable stress at work and that his main concern was his relationship with
      his superior. One of the authors interviewed him using SFA. In the interview the
      worker discovered his own resources and strengths, and finally defined his goal.
      In the end, he discovered solutions by himself, and has been doing well in follow
      up. We describe this process in detail, and discuss potential applications of SFA
      in occupational medicine.

PMID- 15986776
TI  - [A bacteriological study of multiple-drug-resistant Pseudomonas aeruginosa
      isolates derived from 2 patients].
AB  - We investigated the isolation circumstances of multiple-drug-resistant
      Pseudomonas aeruginosa (MDRP) in the UOEH hospital and the bacterial analysis of
      isolated MDRP. From January to October 2003, MDRP was isolated from 2 patients.
      During this period, the isolation frequency of MDRP was 0.57% (2/350). Case 1 had
      2 MDRP isolates from catheter urine, and case 2 had 5 MDRP isolates from pus.
      Regarding serotype, 2 isolates from case 1 were B type and the other 16 isolates
      from case 2 were E type. Pyomelanin was produced by 9 isolates of 16 E type
      isolates. The same PFGE patterns were observed in 2 isolates from case 1; that
      is, 9 pyomelanin producers from case 2 and the other 7 isolates from case 2,
      respectively. Metallo-beta-lactamase was produced by 2 isolates from case 1.
      bla(IMP) was detected from the 2 isolates by PCR, and the clones from case 1 were
      quite different from the clones from case 2. Regarding the pyomelanin producing
      isolates from case 2, although the clones were the same genetically, the MICs of
      imipenem and meropenem increased from 8 to > 32 microg/ml with the progress of
      time. In the UOEH hospital, 6 patients with MDRP isolates have been isolated so
      far, but these 6 patients are not correlated with each other. It is important
      that we detect and report MDRP as early as possible to prevent nosocomial
      infection.

PMID- 15986777
TI  - [A report from the European Clinical Trials Group--new cancer treatment:
      hyperbaric oxygen may be approved for insurance adaptation].

PMID- 15986778
TI  - [Report from the 31st UOEH meeting of Gastrointestinal Image Diagnosis].

PMID- 15986779
TI  - U.S. unprepared for flu outbreak, experts warn.

PMID- 15986780
TI  - Studies say huge malpractice awards are just doctors' empty fears.

PMID- 15986781
TI  - Shrinking budgets, increasing costs plague Medicaid benes.

PMID- 15986782
TI  - Health perception is a unique predictor of anxiety symptoms in non-clinical
      participants.
AB  - This study evaluated the role of perceived health in predicting anxiety symptoms,
      bodily vigilance and agoraphobic cognitions among 71 individuals (30 females;
      mean age 19.9 years, SD=3.1) without a psychiatric history, including non
      clinical panic attacks. Results indicated that, relative to anxiety sensitivity,
      perceived health was a distinct construct that incrementally predicted bodily
      oriented catastrophic thinking (8% of unique variance) and heart-focused anxiety
      (13% of unique variance). Moreover, perceived health significantly incrementally
      predicted anxious arousal symptoms (9% of unique variance). Results are discussed
      in relation to the role of perceived health as a cognitive vulnerability factor
      for anxiety-related problems.

PMID- 15986783
TI  - Cognitive behaviour therapy for panic disorder: long-term follow-up.
AB  - This paper describes a long-term follow-up of patients with panic disorder who
      received cognitive behaviour therapy within a randomized controlled trial. Of 89
      patients eligible for follow-up, 28 (31.5%) were reassessed 6-8 years after
      commencement of treatment in the trial. No differences were found between those
      who were followed up and those lost to follow-up on most baseline measures
      including measures of panic-related psychopathology, or depression. Outcomes at
      long-term follow-up were significantly better than baseline measures of panic,
      avoidance and depression. In this sub-sample the effect of cognitive behaviour
      therapy for panic disorder appears to maintain over the long-term.

PMID- 15986784
TI  - Healthcare utilization following cognitive-behavioral treatment for panic
      disorder with agoraphobia.
AB  - The aim of this study was to examine the overall changes in healthcare services
      utilization after providing an empirically supported cognitive-behavioral
      treatment for panic disorder with agoraphobia. Data on healthcare utilization
      were collected for a total of 84 adults meeting DSM-IV criteria. Participants
      were completers of a cognitive-behavioral treatment for panic disorder with
      agoraphobia. Data on utilization of healthcare services and medication were
      obtained from semi-structured interviews from baseline to 1-year after treatment.
      Results of the Friedman non-parametric analysis reveal a significant decrease in
      overall and mental health-related costs following treatment. This study shows a
      significant reduction in healthcare costs following cognitive behavior therapy
      for panic disorder with agoraphobia. More studies are needed to examine the
      potential long-term cost-offset effect of empirically supported treatments for
      panic disorder.

PMID- 15986785
TI  - Are there interactions among dysfunctional beliefs in obsessive compulsive
      disorder?
AB  - Contemporary cognitive models of obsessive-compulsive disorder emphasize the
      importance of various types of dysfunctional beliefs, such as beliefs about
      inflated responsibility, perfectionism and the importance of controlling one's
      thoughts. These beliefs have been conceptualized as main effects, each
      influencing obsessive-compulsive symptoms independent of the contributions of
      other beliefs. It is not known whether beliefs interact with one another in their
      influence on obsessive-compulsive symptoms. To investigate this issue, data from
      248 obsessive-compulsive disorder patients were analyzed. Dependent variables
      were the factor scores on the 4 Padua Inventory subscales. Predictor variables
      were the factor scores from the 3 factors (inflated responsibility, perfectionism
      and controlling one's thoughts) of the Obsessive Beliefs Questionnaire and their
      2- and 3-way interactions. Regression analyses revealed significant main effects;
      in almost all analyses one or more of inflated responsibility, perfectionism, and
      controlling one's thoughts factors predicted scores on the Padua factors even
      after controlling for general distress. There was no evidence that beliefs
      interact in their effects on obsessive-compulsive symptoms, thereby providing a
      relatively unusual instance in which a simpler explanation (main effects only) is
      just as powerful as a more complex model.

PMID- 15986786
TI  - Hopelessness as a risk factor for post-traumatic stress disorder symptoms among
      interpersonal violence survivors.
AB  - Post-traumatic stress disorder often co-occurs with depression, and they may
      share common risk factors. One possible common cognitive risk factor is
      hopelessness. Thus, we examined whether hopelessness was related to symptoms of
      post-traumatic stress disorder. Participants were 202 female survivors of
      interpersonal violence. Relationships between self-reported and interviewer-rated
      measures of hopelessness gathered at 2 weeks post-trauma and self-reported and
      interviewer-rated symptoms of post-traumatic stress disorder gathered at 2 weeks
      and 3 months post-trauma were examined. Hierarchical, simultaneous regression
      analyses that co-varied trauma type revealed that hopelessness was related to
      self-reported symptoms of post-traumatic stress disorder, both concurrently and
      prospectively. Follow-up analyses revealed that relationships between
      hopelessness and symptoms of post-traumatic stress disorder were due almost
      entirely to shared variance with depression. No relationships were found between
      hopelessness and interviewer-rated symptoms of post-traumatic stress disorder.

PMID- 15986787
TI  - Long-term self-monitoring of weight: a case study.
AB  - The aim of this study was to examine the self-monitoring of weight on a daily
      basis over a long period of time in order to understand the process of weight
      regain. An obese female client measured her weight every morning over a period of
      10 years. The subject made a total of 2081 weight measurements. Thus, her weight
      was measured on 67% of all possible days. After the initial weight loss a pattern
      of gradual weight gain was observed. The subject gained weight during August and
      September, and at the end of December, in particular. Furthermore, her weight
      increased slightly at the weekends. This case study highlights the advantage of
      self-monitoring of weight on a daily basis. Individual patterns of weight change
      possibly associated with season and weekly variation may be crucial when obese
      subjects try to maintain their weight after weight loss. However, it may take
      several months or even years to detect the weekly and yearly rhythms or other
      patterns in the data. Thus, self-control of weight is problematic, since patterns
      in the weight regain process are difficult to detect. This may be one reason why
      self-control of weight is so difficult.

PMID- 15986788
TI  - A burden to others: a common source of distress for the terminally ill.
AB  - Recent research into the desire for death among people with terminal illness has
      begun to recognize the importance of "feeling oneself a burden to others" as a
      factor in suicidal behaviour. In this study, 69 patients with advanced cancer
      underwent semi-structured interviews. The sense of self-perceived burden was
      found to be a common experience, reported by 39.1% of participants as a minimal
      or mild concern and by 38% as a moderate to extreme concern. The sense of burden
      showed a low correlation with physical symptoms (r = 0.02-0.24) and higher
      correlations with psychological problems (r = 0.35-0.39) and existential issues
      (r = 0.45-0.49). Comparisons of participants with high or low levels of self
      perceived burden showed the importance of this factor for overall quality of
      life. In summary, self-perceived burden is an important but underestimated
      dimension of social cognition in the medically ill.

PMID- 15986789
TI  - [Endogenous inflammation and biochemical aspects of pathogenesis of arterial
      hypertension].

PMID- 15986790
TI  - [A micromethod for the determination of the proteolytic activity of blood serum].
AB  - Described in the paper is a micromethod for the determination of the activity of
      proteinases in blood serum by an ELISA-based reader. BAPNA was used as substrate
      for proteolytic enzymes. The method is simple, easily reproducible and cost
      effective--it fits for large-scale examinations.

PMID- 15986791
TI  - [Characteristics of collagen metabolism in duodenal ulcer].
AB  - We studied the content of collagen metabolites in patients with duodenal ulcer
      (blood plasma, urea, and samples of the duodenal mucous tunic and mouth fluid).
      We also defined the role of an affected collagen metabolism in the formation and
      cicatrization of duodenal ulcer; finally, we ascertained that the nature of the
      detected changes in different biological substrate is unidirectional.

PMID- 15986792
TI  - [Diagnostic value of examination of the magnesium homeostasis in children with
      attention deficit syndrome with hyperactivity].
AB  - We followed, within the present case study, 51 children, aged 6 to 11, with
      attention deficit hyperactive syndrome (ADHS); special biochemical tests were
      made. The magnesium level was found to be moderately decreased in plasma and
      erythrocytes and the Mg2+ -ATPase activity was reduced in ADHS children. No
      essential changes of calcium or sodium homeostasis were detected in cells. The
      MAGNE-B6 drug, when used in the complex therapy of ADHS, normalizes the magnesium
      homeostasis, it enhances the large and small motility, attention, psychic
      stability and EEG parameters, and it reduces anxiety. The method of determination
      of magnesium in erythrocytes and in blood plasma can be used to detect the
      deficit of the microelement in patients and to monitor the efficiency of therapy.

PMID- 15986793
TI  - [The activity of adenosinetriphosphatase of erythrocytes in peripheral blood of
      patients with colorectal cancer].
AB  - We studied the activity of whole ATPase, Mg2+ -ATPase and Na+, K+ -ATPase of
      peripheral blood erythrocytes in 68 patients with colorectal cancer before
      surgery and immediately after it and found such activity to be reduced. The low
      activity of Na+, K+ -ATPase of peripheral blood erythrocyte was shown as possible
      for use in prognosticating acute postoperative erosive-ulcerous lesions of the
      gastric tunic. Ozone therapy, if undertaken preoperatively, restores the ATPase
      activity.

PMID- 15986794
TI  - [Mast cells in mastocytosis].

PMID- 15986795
TI  - [Conclusive laboratory medicine (lecture)].

PMID- 15986796
TI  - [Structural and metabolic characteristics of erythrocytes in patients with
      systemic vasculitis].
AB  - We studied the functional and metabolic changes of erythrocytes in systemic
      vasculitis (SV). The below was detected: an increasing intensity of blood
      chemiluminescence, a higher concentration of TBA-positive substances in
      erythrocyte membranes, inhibited Na+, K+ - and Ca2+ -activated and Mg2+ -related
      ATPases in erythrocytes and a reduced osmotic and acidic resistance of
      erythrocytes. An enhanced aggregation ability of erythrocytes and their inhibited
      desagregation were observed in hemorrhagic vasculitis an especially in
      microscopic polyangiitis. The revealed changes characterize the significance of
      the erythrocyte pathology in thrombosis and development of hemorrhagic disorders
      in SV patients.

PMID- 15986797
TI  - [Diagnostic significance of examination of the ciliary epithelium of the
      respiratory tract mucosa].

PMID- 15986798
TI  - [Antibodies as a molecular-diagnostic tool in serodiagnostics and
      seroprognostication of autoimmune myocarditis (literature review)].

PMID- 15986799
TI  - [Changes in the production of immunity-regulating cytokines by blood mononuclear
      cells in chronic herpes virus infection].

PMID- 15986800
TI  - [Serologic examination of patients with prolonged cough in anamnesis].
AB  - Serological examinations of patients with prolonged cough in history, made at an
      allergy center, revealed, in 56% of them, IgG to antigens of Chlamydia pneumoniae
      and C. psittaci; antibodies to M. pneumonie were detected in 25% of them. It is
      expedient to diagnose serologically opportunistic infections in order to prevent
      chronic disease forms and further allergization.

PMID- 15986801
TI  - [Results of development and introduction of programs for quality control of
      laboratory diagnostics of infection diseases in Central Asia].

PMID- 15986802
TI  - [RT-PCR-based evaluation of the activity of human papilloma virus infection in
      relapsing papillomatosis of the larynx].
AB  - RT-PCR-based examination of papilloma samples obtained from patients with
      relapsing papillomatosis of the larynx showed an incidence rate of human
      papilloma virus (HPV) amounting to 89%. The viral load level of the studied
      samples, when measured by concurrent RT-PCR HPV, differed by more than 130 times.
      It made, in the untreated patient, 1.2 x 10(9) hormonal equivalents/ml, i.e. 13
      fold higher versus the patient who received pathogenetic therapy. Thus, the
      approach in question provides for a possibility to monitor the activity of
      papilloma viral infection and to evaluate the efficiency of different variations
      of pathogenetic therapy because the "classic" variant of PCR-detection is not
      informative in the discussed case.

PMID- 15986803
TI  - [Quantitative assessment of delayed antagonism of probiotic cultures against
      opportunistic yeasts].

PMID- 15986804
TI  - [Is it possible to use the certified control materials in the accuracy evaluation
      of clinical laboratory examinations?].

PMID- 15986806
TI  - [Temporary employees, job satisfaction and enlightened choice].

PMID- 15986807
TI  - [Nursing staff responsibilities. Interview by Marie-France Guerel].

PMID- 15986808
TI  - [A supporting story].

PMID- 15986809
TI  - [The 1st graduate education days within the scope of the transfer project
      "nursing education and counseling in home nursing of sick children in Berlin].

PMID- 15986810
TI  - [10 arguments pro recognition of autonomous pediatric home nursing].

PMID- 15986811
TI  - [Anatomy and physiology in word and image "the cardiovascular system"].

PMID- 15986812
TI  - [Hormone replacement therapy--effective in preventing osteoporosis?].

PMID- 15986813
TI  - [Position of the German Professional Organization of Pediatric Nursing in
      reference to updated educational and testing regulation for occupations in
      nursing].

PMID- 15986814
TI  - [Restorative pedagogic developmental support for the chronically ill child].

PMID- 15986815
TI  - [The role of play for self development of the child].

PMID- 15986816
TI  - [May special individual nursing services be rewarded?].

PMID- 15986817
TI  - [Early child rearing--forming a relationship. A glance at general practice].

PMID- 15986818
TI  - [Prevention of language development disorders. Germany is the final member in
      Europe].

PMID- 15986819
TI  - [The efficacy of surgical and conservative methods in secondary prevention of
      carotid ischemic stroke].
AB  - A comparative analysis of the efficacy of surgical and conservative methods in
      secondary prevention of carotid ischemic stroke has been conducted in patients
      with clinical symptoms of acute ischemic brain lesions (carotid artery stenosis
      less than 70%). The results of the 3-year follow-up study revealed that carotid
      endarterectomua is a method of choice. Comparing to conservative therapy, it
      allows a reduction of the absolute risk of secondary ischemic episode development
      to 4% (57% for conservative therapy) and of the relative risk--to 0.07 (0.77 for
      conservative therapy). The necessity of antiaggregate therapy that enables
      increased percentage of strokes prevented is proved. Comparing to aspirin,
      clopidogrel is a drug of choice contributing to the regress of thrombotic layers
      in the cases of restenosis development in the area of sutures after the
      interventions using special patches.

PMID- 15986820
TI  - [Cerebral perfusion in patients with metabolic syndrome].
AB  - Cerebral perfusion was studied in patients with arterial hypertension combined
      with metabolic syndrome and diabetes mellitus type II. The data is compared to
      the results obtained for patients with a single disorder--metabolic syndrome,
      diabetes mellitus type II and arterial hypertension without metabolic
      alterations. It is shown that patients with disregulation of carbohydrate and
      lipid metabolism are more vulnerable to cerebral blood supply alterations. A
      level of perfusion was the same in patients with metabolic syndrome and diabetes
      mellitus type II. Besides, an acetazolamide application revealed that patients
      with metabolic syndrome had reduced cerebral vascular autoregulation.

PMID- 15986821
TI  - [Cerebral hemodynamics and endothelium function in patients with cerebrovascular
      pathology treated by teveten].
AB  - Teveten (eprosartan mesilate) was used as a monotherapy or in combination with
      hypotiazide (12,5 mg/day) in dosage 600 mg once a day for treatment of 20
      patients with cerebrovascular pathology (chronic cerebrovascular insufficiency,
      consequences of brain ischemica in the presence of arterial hypertension stage I
      II, or higher borderline levels of normal blood pressure (BP). Treatment duration
      was 12 weeks, 24-h monitoring of BP was made some indices of cerebral blood flow,
      hemodynamics and peripheral vessels reaction were registered. Modulating
      antihypertensive effect of Teveten was found, statistically significant reduction
      of systolic BP did not result in worsening of cerebral hemodynamics. Moreover,
      there was an improvement of endothelial function. Therefore, teveten may be
      recommended for treatment of patients with cerebrovascular pathology both with
      arterial hypertension and higher borderline BP.

PMID- 15986822
TI  - [Neurological appearances of primary antiphospholipid syndrome].
AB  - Neurological disturbances frequently emerge in antiphospholipid syndrome (APS).
      One hundred and twenty four patients (100 women, 24 men, mean age 37.5 +/- 11.3
      years) with primary APS (PAPS), including 76 patients with Sneddon's syndrome and
      positive antibodies to phospholipids (aPL), have been studied. A structure of
      neurological disturbances was as follows: ischemic lesions of cerebral blood flow
      (LCBF) which comprised stroke and transient LCBF (91%); thrombosis of brain
      venous sinuses (3%); epileptic seizures (24%); headache (65%); chorea (15%);
      visual neuropathy (9%); peripheral neuropathy (6%); multiple-sclerosis-like
      syndrome (10%); myasthenia syndrome (1%); syndrome of parkinsonism of non
      vascular genesis (1%) and psychotic disorders (2%). 84% patients had main
      systemic APS symptoms (fetal loss, thrombosis), which preceded neurological
      appearances in 78% cases. All the patients had aPL: aPL to cardiolipin (aCL)
      and/or lupus coagulant (LC) and/or aPL to phosphatidyl serine, phosphatidyl
      inositol, phosphatidyl ethanolamine. In some patients, aCL titres ranged from
      positive to negative values and LC was not consistently detected. Thus, the
      presence of clinical symptoms of PAPS including neurological disturbances demands
      an investigation of different aPL types as well as a replicate study for
      immunological confirmation of PAPS.

PMID- 15986823
TI  - [The normoxic therapeutic compression effect on microcirculation in acute
      stroke].
AB  - The study evaluates efficacy of two hyperbaric therapeutic regimes--1,-51,1 atm
      and 1,2 atm in patients with an acute ischemic stroke. Acid-base equilibrium
      dynamics of capillary and venous blood, whole blood and plasma, platelet
      aggregation and lipid peroxidation were investigated. An analysis of the data
      revealed that, comparing to the conventional method, barotherapy in stroke is
      accompanied by a marked therapeutic effect. Barotherapy or normoxic therapeutic
      compression is principally different from other methods of oxygen therapy,
      because it is not resultant in blood plasma hyperoxygenation and in lipid
      peroxidation augmenting. Activation of tissue respiration in barotherapy
      accompanied by normalization of lipid peroxidation process and CO2 resources
      restoration leads to renewal of MKT microcirculation and autoregulation, thus
      providing a stable therapeutic effect of the method in brain ischemia.

PMID- 15986824
TI  - [The influence of coronary artery bypass graft surgery on cerebral hemodynamics].
AB  - The influence of coronary artery bypass graft surgery (CABGS) on cerebral
      hemodynamics is still understudied. At the same time, ischemic heart disease
      (IHD) is often comorbid to atherosclerotic carotid artery stenosis, with
      significantly higher risk of post CABGS cerebrovascular complications in patients
      with cerebral hemodynamics lesion. Indices of cerebral hemodynamic reserve have
      been studied in 40 patients with severe IHD before and after CABGS. In most
      patients, there was a significant postoperative improvement of cerebral
      hemodynamics related to enhancing of blood flow along medial cerebral arteries
      and to amelioration of the parameters of cerebral hemodynamic reserve. But CABGS
      did not positively impact on cerebral hemodynamics in patients with initially
      reduced ejection fraction that appears to be a consequence of insufficient
      increase of stroke volume and in patients with a history of ischemic lesions of
      cerebral blood circulation. Therefore, the results obtained suggest a close
      relationship between coronal and cerebral blood circulation that should be taken
      into account in the analysis of pathogenetic mechanisms of cerebral blood
      circulation lesion in patients with IHD as well as in elaboration of adequate
      individual preventive treatment measures.

PMID- 15986825
TI  - [A study of the risk factors of stroke development in the framework of WHO
      program "MONICA-psychosocial"].
AB  - The study was conducted in the framework of WHO program "MONICA--psychosocial" in
      1994-2002 using a randomized representative sample of males aged 25-64 years
      recruited from one district of Novosibirsk city. Over 8 years all stroke cases in
      the cohort have been registered and relative risk (RR) of stroke development was
      determined by special statistical methods. RR proved to be higher as follows: in
      males with depression--5,9-fold; with life exhaustion--3-fold; with low index of
      close relation--3-fold; with low index of social relations--4-fold; with sleep
      disturbance--2,7-fold; with stressful events in the family--2-fold; with
      stressful events at the job--4-fold. High level of hostility did not exert any
      influence on stroke development. Most frequently stroke occurred in men with
      higher negative psychosocial factors, i.e. widowers, divorced, those with primary
      and not-completed secondary school education and those engaged in hard and
      moderate manual labor as well as pensioners and individuals with low social
      support.

PMID- 15986826
TI  - [Vertebrogenic and atherosclerotic mechanisms of vertebral basilar insufficiency:
      comparative ultrasonic characteristics].
AB  - Using a complex of ultrasonic methods, vertebral basilar system hemodynamics has
      been evaluated in normal state and in case of vertebral basilar insufficiency
      (VBI). The differential diagnostic criteria of atherosclerotic and vertebrogenic
      types of VBI development have been obtained that enables to individualize the
      therapeutic approaches.

PMID- 15986827
TI  - [Distribution of erythrocyte antigens in patients with brain stroke].
AB  - Immunogenetic structure for erythrocyte antigens was studied in 40 patients with
      brain stroke in East Kazakhstan. The results of a clinicoimmunogenetic analysis
      suggest significant positive and negative associations between erythrocyte
      antigens and stroke. Antigenes M+; Le(epsilon); Kell-, Cw were associated with a
      higher risk of brain stroke in Kazakh population.

PMID- 15986828
TI  - [Dynamics of nitric oxide dependant oxidative stress in acute stage of ischemic
      stroke].
AB  - Fifty-eight patients with acute ischemic stroke have been studied. The basic
      neurological impairment was assessed with the National Institute of Health Stroke
      Scale (NIHSS) and the Glasgow Coma Scale (GCS). The patients were stratified by
      stroke severity into 2 groups: 1--with severe stroke (GCS> 9; NIHSS > 15) and 2-
      with stroke of moderate severity (GCS = 14-15; NIHSS = 10-15). Visualization of
      ischemic injury was performed by conventional Magnetic Resonance Imaging (MRI) 24
      hours after stroke onset. Nitric oxide (NO) levels were measured by Electron
      Paramagnetic Resonance (EPR) method and NO2 and superoxidedismutase (SOD) levels
      were defined by spectrophotometer. Comparing to controls, intensive EPR signals
      for free NO were found in the groups of patients during 48 hours after stroke
      onset, though no between-group differences were detected. In group 2, CSF SOD and
      NO2 levels were significantly higher than in group 1 and controls. There was a
      significant negative correlation between initial NO2 CSF levels and ischemic
      lesion size as well as functional outcome 1 month after stroke onset. Thus, CSF
      NO2 levels in acute stage of ischemic stroke can be considered as an important
      predictor of the disease course and functional outcome.

PMID- 15986829
TI  - [Hemodynamic reserve (analytical review)].

PMID- 15986830
TI  - [A role of neuropsychological studies in survivors of ischemic stroke (review)].

PMID- 15986831
TI  - Ecological and agricultural significance of bacterial polyhydroxyalkanoates.
AB  - Polyhydroxyalkanoates (PHAs) are a group of carbon andenergy storage compounds
      that are accumulated during suboptimal growth by many bacteria, and
      intracellularly deposited in the form of inclusion bodies. Accumulation of PHAs
      is thought to be used by bacteria to increase survival and stress tolerance in
      changing environments, and in competitive settings where carbon and energy
      sources may be limited, such as those encountered in the soil and the
      rhizosphere. Understanding the role that PHAs play as internal storage polymers
      is of fundamental importance in microbial ecology, and holds great potential for
      the improvement of bacterial inoculants for plants and soils. This review
      summarizes the current knowledge on the ecological function of PHAs, and their
      strategic role as survival factors in microorganisms under varying environmental
      stress is emphasized. It also explores the phylogeny of the PHA cycle enzymes,
      PHA synthase, and PHA depolymerase, suggesting that PHA accumulation was earlier
      acquired and maintained during evolution, thus contributing to microbial survival
      in the environment.

PMID- 15986832
TI  - Diversify or die: generation of diversity in response to stress.
AB  - When challenged with unfavorable conditions, microorganisms can develop a stress
      response that allows them to adapt to or survive in the new environment. A common
      feature of the numerous specific stress response pathways that have been
      described in a wide range of bacteria is that they are energy demanding and
      therefore often transient. In addition, stress responses may come too late or be
      insufficient to protect the cell or the population against very sudden or severe
      stresses. However, it seems that microorganisms can also enhance their chances of
      survival under stress by increasing the generation of diversity at the population
      level. This can be achieved either by creating genetic diversity by a variety of
      mechanisms involving for example constitutive or transient mutators and
      contingency loci, or by revealing phenotypic diversity that remained dormant due
      to a mechanism called genetic buffering. This review gives an overview of these
      emerging diversity-generating mechanisms, which seem to play an important role in
      the ability of microbial populations to overcome stress challenges.

PMID- 15986833
TI  - Effects of enhanced ultraviolet-B radiation on algae and cyanobacteria.
AB  - This article provides an overview of existing literature on the ultraviolet-B (UV
      B) radiation effects on algae and cyanobacteria. We report on the effects of UV-B
      radiation to the growth and development, biomass, sensitivity, photosynthetic
      pigments, UV-B absorbing compounds, photosynthesis, protein and DNA damage,
      enzyme activity, nitrogen fixation and assimilation of nitrogen, protective
      mechanisms of algae and cyanobacteria, the accommodation of algae and
      cyanobacteria to environmental stress, and the effects to ecology system. Many of
      the studies show the dramatic effects of UV-B radiation; but typically these
      studies were conducted under conditions with supplemental UV-B irradiance that
      was higher than would ever occur outside experimental conditions or natural
      condition. A few of the studies reviewed used experimental conditions and
      supplemental UV-B irradiance that approached realism. Enhanced UV-B generally
      decreased chlorophyll content, whereas it increased UV-B absorbing compounds in
      many algae. Decrease in photosynthesis, particularly at higher UV-B doses, was
      due to both direct (effect on photosystem) and indirect (decrease in pigments)
      effects. The decreases in chlorophyll pigments and photosynthesis resulted in
      lower biomass. However, algae and cyanobacteria have evolved various avoidance
      and repair mechanisms to protect themselves against the damaging effects of UV
      radiation to acclimate to enhanced UV-B radiation. The review points to areas
      where further studies on the relationships among nitrogenase, Rubisco,
      antioxidase activity, signal, antioxidants, and free radicals under enhanced UV-B
      are needed to quantify the effects of UV-B radiation on algae and cyanobacteria.
      These studies are needed in order to develop dose response functions that can
      facilitate development of dynamic simulation models for use in UV-B and other
      environmental impact assessments.

PMID- 15986834
TI  - Protein signatures distinctive of alpha proteobacteria and its subgroups and a
      model for alpha-proteobacterial evolution.
AB  - Alpha (alpha) proteobacteria comprise a large and metabolically diverse group. No
      biochemical or molecular feature is presently known that can distinguish these
      bacteria from other groups. The evolutionary relationships among this group,
      which includes numerous pathogens and agriculturally important microbes, are also
      not understood. Shared conserved inserts and deletions (i.e., indels or
      signatures) in molecular sequences provide a powerful means for identification of
      different groups in clear terms, and for evolutionary studies (see
      www.bacterialphylogeny.com). This review describes, for the first time, a large
      number of conserved indels in broadly distributed proteins that are distinctive
      and unifying characteristics of either all alpha-proteobacteria, or many of its
      constituent subgroups (i.e., orders, families, etc.). These signatures were
      identified by systematic analyses of proteins found in the Rickettsia prowazekii
      (RP) genome. Conserved indels that are unique to alpha-proteobacteria are present
      in the following proteins: Cytochrome c oxidase assembly protein Ctag, PurC,
      DnaB, ATP synthase alpha-subunit, exonuclease VII, prolipoprotein
      phosphatidylglycerol transferase, RP-400, FtsK, puruvate phosphate dikinase,
      cytochrome b, MutY, and homoserine dehydrogenase. The signatures in succinyl-CoA
      synthetase, cytochrome oxidase I, alanyl-tRNA synthetase, and MutS proteins are
      found in all alpha-proteobacteria, except the Rickettsiales, indicating that this
      group has diverged prior to the introduction of these signatures. A number of
      proteins contain conserved indels that are specific for Rickettsiales (XerD
      integrase and leucine aminopeptidase), Rickettsiaceae (Mfd, ribosomal protein
      L19, FtsZ, Sigma 70 and exonuclease VII), or Anaplasmataceae (Tgt and RP-314),
      and they distinguish these groups from all others. Signatures in DnaA, RP-057,
      and DNA ligase A are commonly shared by various Rhizobiales, Rhodobacterales, and
      Caulobacter, suggesting that these groups shared a common ancestor exclusive of
      other alpha-proteobacteria. A specific relationship between Rhodobacterales and
      Caulobacter is indicated by a large insert in the Asn-Gln amidotransferase. The
      Rhizobiales group of species are distinguished from others by a large insert in
      the Trp-tRNA synthetase. Signature sequences in a number of other proteins (viz.
      oxoglutarate dehydogenase, succinyl-CoA synthase, LytB, DNA gyrase A, LepA, and
      Ser-tRNA synthetase) serve to distinguish the Rhizobiaceae, Brucellaceae, and
      Phyllobacteriaceae families from Bradyrhizobiaceae and Methylobacteriaceae. Based
      on the distribution patterns of these signatures, it is now possible to logically
      deduce a model for the branching order among alpha-proteobacteria, which is as
      follows: Rickettsiales --> Rhodospirillales-Sphingomonadales --> Rhodobacterales
      Caulobacterales --> Rhizobiales (Rhizobiaceaea-Brucellaceae-Phyllobacteriaceae,
      and Bradyrhizobiaceae). The deduced branching order is also consistent with the
      topologies in the 16 rRNA and other phylogenetic trees. Signature sequences in a
      number of other proteins provide evidence that alpha-proteobacteria is a late
      branching taxa within Bacteria, which branched after the delta,epsilon
      subdivisions but prior to the beta,gamma-proteobacteria. The shared presence of
      many of these signatures in the mitochondrial (eukaryotic) homologs also provides
      evidence of the alpha-proteobacterial ancestry of mitochondria.

PMID- 15986835
TI  - Gulf War Syndrome-the story so far.

PMID- 15986836
TI  - Deliberate self harm in the Royal Navy. An audit of cases presenting to the
      Department of Community Mental Health, RH Haslar between 1 March 1999 and 28
      February 2002.

PMID- 15986837
TI  - How to TRiM away at post traumatic stress reactions: traumatic risk management-
      now and the future.

PMID- 15986838
TI  - Historical reflections on mental health at Haslar 1753-2003.

PMID- 15986839
TI  - The psychological morbidity of military healthcare workers.
AB  - OBJECTIVE: To measure the probable prevalence of psychological morbidity in
      military healthcare professionals using the General Health Questionnaire 28.
      RESULTS: 21 (35%) of military healthcare workers showed psychological ill health.
      Royal Air Force health staff had a significantly higher prevalence of ill health
      than both the Army [12 (63%) vs 6 (23%)] and the Royal Navy [12 (63%) vs 1 (8%)].
      RAF non-commissioned staff were found to have a highly significant prevalence of
      ill health compared to the Army non-commissioned staff [7(70%) vs 1 (7%)], and
      Royal Navy non-commissioned staff [7 (70%) vs 0 (0%)]. CONCLUSION: The study
      shows significant differences in psychological ill health between Services at the
      RCDM. Comparison with civilian data showed that the overall prevalence of
      psychological morbidity was no higher than in NHS staff. The elevated level of
      ill health in the Royal Air Force staff warrants further investigation and
      possible intervention.

PMID- 15986840
TI  - In-hospital prevention of cardiac arrest.

PMID- 15986841
TI  - Patients' perception of military doctors in fracture clinics--does the wearing of
      uniform make a difference?
AB  - We performed a study during our Trauma Week when patients who were referred from
      the accident department with fractures were reviewed in our fracture clinic.
      During our Trauma Week, Mister Thomas, Consultant Orthopaedic and Trauma Surgeon
      or Surgeon Lieutenant Commander McLean, Specialist Registrar in Orthopaedic and
      Trauma Surgery reviewed a total of 93 patients in fracture clinic. All patients
      were given an anonymous questionnaire regarding their perceptions of their
      attending clinician, 77 were completed. Forty-nine questionnaires regarding
      Surgeon Lieutenant Commander McLean and 28 regarding Mister Thomas were available
      for analysis. During the Trauma Week all patients were seen in the same location
      in identical cubicles by either of the two clinicians, consultations were
      typically brief lasting about five minutes. Throughout the week the clinicians,
      one military and one civilian, wore differing attire. The military uniform
      comprised Royal Navy number four action working dress. The civilian attire
      comprised 'dog-robbers' (jacket, shirt with tie and smart trousers). The
      hypothesis tested was that the use of military uniform might alter patients'
      perceptions of their attending clinician. Our results appear to demonstrate that
      the attire of the attending clinician does not adversely influence patients'
      perceptions of their attending clinician.

PMID- 15986842
TI  - Case report: Use of a remifentanil infusion with the tri-service anaesthetic
      apparatus.
AB  - During a recent deployment to Iraq, it was noticed that patients' recovery times
      from general anaesthesia were significantly prolonged. We postulated that this
      was because of a lack of nitrous oxide--thereby creating a requirement for
      greater concentrations of volatile agent to maintain adequate depth of
      anaesthesia. We chose to adopt the technique of running a remifentanil infusion
      with the Tri-Service apparatus in an attempt to reduce the administered volatile
      and thus shorten recovery times.

PMID- 15986843
TI  - Rememberance of a D-Day medic.

PMID- 15986844
TI  - Measurement of gastrointestinal transit.
AB  - An abnormality in transit is commonly considered to account for unexplained
      gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap
      with those of accelerated transit, direct measurement of GI transit is needed to
      establish an accurate diagnosis. Similarly, since symptoms originating from one
      part of the gut may overlap with symptoms from another, localizing transit
      abnormality to one organ vs. another using direct measurement is an important
      part of diagnostic evaluations. Consequently, noninvasive tests of GI transit
      should be done early in the evaluation to guide therapy. We now have tools to
      measure transit accurately; results of transit tests often depend on the
      conditions selected for the test, so test results will match clinical
      expectations most closely when test conditions are selected to reproduce the
      circumstances for symptom production. This review describes the most commonly
      used methods for the measurement of GI transit including the gastric emptying
      test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms
      and diarrhea, colonic transit test for constipation, and factors that influence
      the result of these studies. As we make progress in our understanding of the
      pathophysiology of transit disorders, the clinical usefulness of these diagnostic
      tests will be further enhanced.

PMID- 15986845
TI  - A pilot study of the effects of sildenafil on stool characteristics, colon
      transit, anal sphincter function, and rectal sensation in healthy men.
AB  - Nitric oxide is an important mediator of gut smooth muscle relaxation and
      visceral sensation. Sildenafil results in stimulation of the nitric oxide-cyclic
      GMP pathway. We sought to determine the effects of daily sildenafil
      administration on colorectal function. Over a 4-week period, sildenafil was
      administered during weeks 2 and 3. Stool frequency and consistency were assessed
      daily. Anorectal manometry, rectal sensation, and colon transit testing were
      performed at the end of weeks 1 and 3. Ten healthy men were studied. No
      significant differences in segmental or total colon transit time were noted;
      however, significant changes in stool frequency and trends toward decreased stool
      consistency were noted during sildenafil use. A trend toward reduced resting anal
      sphincter pressure was seen after sildenafil. Rectal volumes to first sensation
      and desire to defecate were significantly increased after sildenafil on test day
      2 only. Additionally, volumes to desire to defecate and maximal tolerable volume
      were significantly increased before sildenafil on test day 2 compared to before
      sildenafil on test day 1. We conclude that daily administration of sildenafil is
      well tolerated and results in alterations in colorectal function.

PMID- 15986846
TI  - Chronic gastritis is not associated with gastric dysrhythmia or delayed solid
      emptying in children with dyspepsia.
AB  - To determine if chronic gastritis (CG) is associated with gastric dysrhythmia or
      delayed solid emptying in children with dyspepsia, 22 patients (7-15 years of
      age) with dyspepsia and normal gross endoscopies were studied. Antral biopsies
      were evaluated for chronic gastritis, and immunohistology was performed to
      determine densities of CD3+, CD20+, CD25+, and tryptase-positive cells.
      Electrogastrography (EGG) and gastric scintiscan evaluation were performed within
      2-7 days of endoscopy. CG and increased immune cell densities were not associated
      with altered gastric emptying. Mean CD3+ cell counts were positively correlated
      with the percentage normal slow waves, and patients with a normal EGG had
      increased CD3+ cell density. In children with dyspepsia, chronic antral
      inflammation in the setting of a normal gross endoscopy is not associated with
      EGG abnormalities or delayed solid emptying. Chronic gastritis and gastric
      dysrhythmia may simply be two separate and distinct mechanisms resulting in the
      clinical entity of dyspepsia.

PMID- 15986847
TI  - Stem cell factor (SCF) and interleukin 3 (IL-3) in the sera of patients with
      colorectal cancer.
AB  - For a long time markers that can detect a malignant cell transformation as early
      as possible have been sought. Substances which have been discovered are known as
      tumor markers. Stem cell factor (SCF) and interleukin 3 (IL-3) are members of a
      group of glycoprotein growth factors called hematopoietic cytokines (HCs). These
      factors take part in the regulation of developmental processes of hematopoietic
      progenitor cells and it was proved that HCs can be produced by different cancer
      cells, including colorectal cancer. The aim of this study was to investigate a
      potential role for SCF and IL-3 as tumor markers for colorectal cancer. We
      compared the serum levels of SCF and IL-3 in colorectal cancer patients with
      those in healthy subjects (control group) and commonly accepted tumor markers,
      such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9).
      We defined the diagnostic sensitivity, specificity, positive predictive value,
      negative predictive value, and receiver-operating characteristics (ROC) curve of
      tested substances. SCF and IL-3 were determined using enzyme-linked immunosorbent
      assay (ELISA). CEA and CA 19-9 were measured by microparticle enzyme immunoassay.
      The serum levels of HCs and tumor markers were investigated in 75 patients with
      colorectal cancer and in 40 healthy subjects. There were significant differences
      in the level of circulating SCF and IL-3 in the colorectal cancer patients
      compared to the control group. Moreover, the diagnostic sensitivity of SCF was
      higher than the sensitivity of CEA and CA 19-9. The SCF area under the ROC curve
      was larger than the IL-3 area but smaller than the CEA and CA 19-9 areas. The
      diagnostic specificities of cytokines were lower than those of tumor markers, but
      the combined use of cytokines and tumor markers increased the diagnostic values.
      The highest values of diagnostic parameters were observed for the combined use of
      SCF and CA 19-9. These results suggest a potential role for SCF and IL-3 as tumor
      markers for colorectal cancer, especially in combination with CEA or CA 19-9.

PMID- 15986848
TI  - Apoptosis induced by aspirin and 5-fluorouracil in human colonic adenocarcinoma
      cells.
AB  - Various biochemical, clinical and epidemiological studies have shown that aspirin
      (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) demonstrate
      antineoplastic properties, particularly in the gastrointestinal tract, inhibiting
      the proliferation of colorectal cancer cells. The mechanism of action may be
      prostaglandin mediated through inhibition of the COX enzymatic system. This
      includes two iso-enzymes, COX-I and COX-II, working in concert with the
      activation of apoptosis, activation of immune surveillance, inhibition of
      proliferation, and inhibition of carcinogen activation. 5-Fluorouracil (5-FU) has
      demonstrated activity against colorectal cancer, leading to apoptosis of
      neoplastic cells. We evaluated the effects of varying doses of ASA (0.5, 1, 1.5
      mM), both as a single agent and in combination with 5-FU (50 microg) in HT-29, a
      colon adenocarcinoma cell line. Proliferation assays showed that aspirin at a
      concentration of 1 mM inhibits cell growth. Cells treated with ASA, both alone
      and in combination with 5-FU, demonstrated apoptotic activity with the up
      regulation of Bax protein, which is consistent with 5-FU anticancer treatment.
      Furthermore, there was synergistic cell death with ASA and 5-FU. DNA
      fragmentation, TUNEL, and trypan blue exclusion methods indicated that a
      combination of ASA and 5-FU induces apoptosis in cells in a time- and
      concentration-dependent manner. This study serves to further elucidate the
      mechanism of action of ASA, and ASA in combination with 5-FU, in colorectal
      cancer as evidenced by its effect on the HT-29 cell line.

PMID- 15986849
TI  - An unusual presentation of colon cancer in a young individual.
AB  - Intussusception occurs rarely in adults. It presents with a variety of acute,
      intermittent, and chronic symptoms, thus making its preoperative diagnosis
      difficult. CT scan of the abdomen and pelvis usually reveals the diagnosis of
      intussusception in adults. Surgical resection of the intussusception without
      reduction is the preferred treatment in adults, as almost half of both colonic
      and enteric intussusceptions are associated with malignancy. However, the choice
      and timing of operation will depend on the clinical condition of the patient and
      the status of the invaginating tumor. Colon cancer in young individuals is
      usually aggressive, with a dismal prognosis.

PMID- 15986850
TI  - MR enteroclysis: imaging technique of choice in diagnosis of small bowel
      diseases.
AB  - MR enteroclysis is becoming a very important imaging modality in the workup and
      follow-up of small bowel diseases. The technique has many advantages, including
      the absence of ionizing radiation, ability to control luminal distension,
      superior tissue characterization, multiplanar capabilities, and mural and
      extramural visualization. These capabilities can be obtained with a simple
      protocol showing excellent agreement with conventional enteroclysis. In 29 (18
      with new or known Crohn's disease) of the 50 patients pathology was detected,
      with a very good clinical correlation. In 14 patients MR enteroclysis data
      altered the therapeutic strategy. This contributes to the acceptance of this
      modality as a primary tool in small bowel diseases.

PMID- 15986851
TI  - Double balloon enteroscopy-the last blind-point of the gastrointestinal tract.
AB  - Technical challenges have obstructed the diagnosis and treatment of small
      intestine disease. An innovative form of enteroscopy-the double balloon method
      permits visualization of the complete small intestine, to-and-fro examination of
      an area of interest, and biopsy and endoscopic procedures which are safer,
      faster, and less painful than earlier methods. From October 2003 to May 2004, a
      total of 10 patients with obscure gastrointestinal bleeding received 12
      enteroscopic examinations, 8 per oral and 4 per rectal examinations, while 2
      patients received per oral enteroscopy first and further per rectal procedures 2
      days later. Two cases with intestinal submucosal tumors were discovered by per
      oral enteroscopy, one with a 5-cm SMT with reddish mucosa at the jejunum and
      another with a 4-cm SMT and surface ulceration, in which the biopsy showed GIST.
      Both patients received an operation later. Four patients were found to have
      intestinal angiodysplasia in jejunum(per oral) and one in ileum (per rectal), and
      after local therapy bleeding stopped. Multiple angiodysplasias were observed in a
      patient who was operated on for active bleeding from the ileum after Indian ink
      tattooing. The two patients who received per oral and per rectal procedures did
      not display definite small intestinal lesions. All patients underwent the
      procedures satisfactorily without any complications, and the examination times
      varied from 90 to 360 min. Double balloon enteroscopy permits deep insertion of
      an endoscope into the small intestine without excessive stretching of the
      intestinal tract. This method can use either an oral or an anal approach. To-and
      fro observation of almost the complete small intestine is possible, as are
      interventions.

PMID- 15986852
TI  - Inhibition of bacterial adherence on the surface of stents and bacterial growth
      in bile by bismuth dimercaprol.
AB  - Bacterial infection and biofilm formation on the surface of biliary stents is
      believed to be one of the main factors in stent occlusion. This study explored
      the role of the new reagent, bismuth dimercaprol, in preventing bacterial
      adherence and bacterial biofilm formation on the surface of biliary stents.
      Sterile porcine bile preparations, infected separately with Escherichia coli,
      Klebsiella pneumoniae, Enterobacter, and Enterococcus, were used as the perfusion
      media in an in vitro perfusion system. The bacterial growth in the media and the
      bacterial adherence on the surface of stents were tested when different
      concentrations of bismuth dimercaprol were used in the perfusion media. BisBAL (5
      microM) did not inhibit the growth of any of the tested bacterial species. It
      did, however, significantly decrease the amount of bacteria adhering to the
      surface of stents for all bacterial strains except Escherichia coli. Bismuth
      dimercaprol (20 microM) significantly inhibited the growth of Escherichia coli,
      Klebsiella pneumoniae, and Enterobacter and, thereby, significantly decreased the
      amount of these bacteria adhering to the surface of stents. The unique
      bactericidal and anitbiofilm activities of bismuth thiols might contribute to
      delaying the process of biliary stent occlusion if the effective concentrations
      of bismuth thiols could be delivered to the target sites. The feasibility of this
      application of bismuth thiols deserves further investigation.

PMID- 15986853
TI  - High prevalence of hypothyroidism in patients with autoimmune pancreatitis.
AB  - Autoimmune pancreatitis is a unique form of chronic pancreatitis and has been
      correlated with various extrapancreatic lesions. To search for a correlation
      between autoimmune pancreatitis and thyroid lesions, we measured thyroid
      functions in 41 patients with autoimmune pancreatitis and in 41 patients with
      chronic calcifying pancreatitis and investigated the correlation between HLA
      antigens and hypothyroidism. We found a significant difference in the prevalence
      of antithyroglobulin antibody and hypothyroidism between patients with autoimmune
      pancreatitis and those with chronic pancreatitis (34.1 vs. 7.3%, P = 0.005, and
      26.8 vs. 0%, P = 0.0005, respectively). Patients with hypothyroidism had a
      significantly higher frequency of antithyroglobulin antibody (63.6%) than those
      without hypothyroidism but showed no differences in other findings, including
      serum IgG4 concentration. We could find no significant association between any
      HLA antigens and the hypothyroid state of autoimmune pancreatitis. One quarter of
      the patients with autoimmune pancreatitis have hypothyroidism that may be
      independent of the active state of the pancreatic lesion or systemic fibrosing
      disorder, and thus patients suspected of having autoimmune pancreatitis should be
      evaluated for possible hypothyroidism.

PMID- 15986854
TI  - Comparison of inulin and lactulose as reference standards in the breath hydrogen
      test assessment of carbohydrate malabsorption in patients with chronic pancreatic
      exocrine insufficiency.
AB  - Although often used as a reference standard in the breath hydrogen test (BHT),
      lactulose fermentation produces more hydrogen, compared to starch, and may
      therefore not be ideal. This study compares inulin with lactulose as reference
      standard in the study of carbohydrate malabsorption. Seventeen patients with
      malabsorption due to chronic pancreatitis and 15 normal controls were studied.
      Following overnight fasts, BHTs were performed after ingesting 10 g lactulose, 10
      g inulin, and 200 g (16 g highly resistant starch) maize meal. Lactulose
      fermentation produced significantly more hydrogen than inulin in patients with
      malabsorption (97 +/- 20 vs 45 +/- 22 ppm x hr; P < 0.05) and controls (43 +/- 18
      vs 21 +/- 10 ppm x hr; P < 0.05). Patients produced more hydrogen than controls
      with both standards (lactulose, 97 +/- 20 vs 43 +/- 18 ppm x hr, P < 0.05; inulin
      45 +/- 22 vs 21 +/- 10 ppm x hrs; P < 0.05), suggesting adaptation of the colonic
      flora. Calculated CHO malabsorption was 2.5 +/- 0.8 vs 5.2 +/- 3.8 g with
      lactulose and 5.2 +/- 3.1 vs 11.2 +/- 9.6 g with inulin as standards in controls
      and patients, respectively (P < 0.05). Lactulose produces more breath hydrogen
      than inulin. Calculation of CHO malabsorption using these standards is therefore
      not comparable.

PMID- 15986855
TI  - Acute pancreatitis in patients with ulcerative colitis.
AB  - Twenty-two patients (13 men and 9 women; median age, 34 years; range, 15-64
      years) with ulcerative colitis (UC) were evaluated to determine the incidence of
      acute pancreatitis with UC at the First Department of Internal Medicine, Mie
      University School of Medicine, during 1989-2001. Among these, three patients
      (14%) were diagnosed as having had episodes of acute pancreatitis during the mean
      follow-up period of 6 years. One patient presented with acute pancreatitis and UC
      simultaneously. Two patients had drug-induced pancreatitis (one due to
      azathioprine and the other due to 5-ASA). In conclusion, acute pancreatitis is
      not a frequent, but an occasional extraintestinal manifestation of UC.

PMID- 15986856
TI  - Multiple myeloma involving the porta hepatis and peritoneum causing biliary
      obstruction and malignant ascites.

PMID- 15986857
TI  - Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism
      of gastroesophageal reflux but are not the cause of reflux disease.
AB  - In healthy subjects, the rate of acid reflux during transient lower esophageal
      sphincter relaxations (TLESRs) is more frequent at the proximal margin of the
      LES. In this study, we investigated the hypothesis that the rate of acid reflux
      at the proximal margin of LES during TLESRs is similar in reflux disease to that
      in healthy subjects. Concurrent esophageal manometry and pH monitoring were
      performed in the sitting position for 3 hr after a standard meal in 10 patients
      with reflux disease and 10 age-matched healthy controls. The rate of TLESRs in
      patients with reflux disease (5.0/hr [3.3-6.7]; median [interquartile range]) was
      similar to that of controls (4.5/hr [3.7-5.7]). The incidence of acid reflux 7 cm
      above the LES during TLESRs in patients (48.1% [27.2-71.4%]) was significantly
      higher than that in controls (10.9% [0.0-18.8%]) but there was no difference 2 cm
      above the LES (75.0 [69.2-87.5] vs. 74.3 [55.5-90.0%]). The rate of TLESRs and
      the incidence of acid reflux during TLESRs are not increased in reflux disease.
      These findings, therefore, indicate that reflux disease is not a disorder of
      TLESRs and relates more to the proximal extent of the refluxate.

PMID- 15986858
TI  - Infection with Helicobacter pylori affects all major secretory cell populations
      in the human antrum.
AB  - We have investigated how gastric H. pylori infection affects antrum secretory
      cell types by studying the expression of secretory proteins in antrum epithelium.
      Antrum biopsy specimens were prospectively collected from 102 individuals (49 H.
      pylori-infected). Immunohistochemistry was performed for secretory mucins
      (MUC5AC, MUC5B, MUC6), Trefoil factor family (TFF)-peptides (TFF1, TFF2),
      endocrine peptides (gastrin, chromogranin A), and proliferating cells (Ki-67).
      Protein expression was quantified morphometrically. H. pylori infection was
      significantly correlated to mucosal inflammation and to epithelial atrophy and
      proliferation. In H. pylori-infected patients the number of proliferating cells
      increased significantly, and the zone of proliferating cells shifted toward the
      surface epithelium of the antral glands. Infection was correlated with decreased
      MUC5AC, TFF1, and TFF2 expression and increased MUC6 and MUC5B expression.
      Endocrine cells expressing chromagranin A and gastrin shifted toward the surface
      epithelium of the antral glands in H. pylori-infected patients. H. pylori
      infection and concomitant inflammation induced increased epithelial proliferation
      and triggered coordinate deregulation of secretory cell populations in the
      antrum. In particular, infection led to a coordinated increase in cells
      expressing MUC6 and MUC5B at the expense of MUC5AC-producing cells.

PMID- 15986859
TI  - Gastric mucosa epithelial cell kinetics are differentiated by anatomic site and
      Helicobacter pylori infection.
AB  - Changes in epithelial cell turnover related to Helicobacter pylori infection may
      contribute to gastric cancer development. The response of different anatomic
      sites of the gastric mucosa to H. pylori is not known. We studied apoptosis and
      cell proliferation at the grater and lesser curvature of the antrum and corpus,
      the fundus, and the cardia from 9 H. pylori gastritis patients and 11 H. pylori
      negative controls with normal histology. Proliferation was highest at the major
      curve of the antrum and lowest at the fundus, and apoptosis was highest at the
      cardia and lowest at the major curve of the antrum in both H. pylori gastritis
      and normal mucosa. Proliferation was significantly higher at all anatomic sites,
      while apoptosis was significantly lower only at the major and lesser curve of the
      corpus in H. pylori gastritis compared with normal controls. Our data suggest
      that gastric mucosa epithelial cell kinetics is differentiated by the anatomic
      site and H. pylori infection.

PMID- 15986860
TI  - Direct transmission of H. pylori from challenged to nonchallenged mice in a
      single cage.
AB  - To understand whether direct transmission of H. pylori occurs from infected mouse
      to noninfected mouse, the system using a mouse model we developed previously was
      tested. Six nude mice were challenged with H. pylori inocula; one group consisted
      of one challenged nude mouse 1 week after inoculation raised with four
      nonchallenged nude mice in a single cage. For the single cage, a polycarbonate
      cage or a mesh-floor cage was used. Then three groups were kept in a
      polycarbonate cage and the other three groups kept in a mesh-floor cage to avoid
      H. pylori transmission through stool. After coraising for 1, 2, or 3 weeks, all
      mice were sacrificed to determine the existence of H. pylori in the stomach,
      saliva, and stool by culture or PCR and H. pylori-associated gastritis. RAPD
      fingerprinting patterns using different primers of isolated strains from
      challenged and nonchallenged mice were compared to understand the origin of
      transmitted strains. During 3 weeks after coraising of H. pylori challenged and
      nonchallenged mice, H. pylori was detected in the stomachs in 3 of 12
      nonchallenged mice in the polycarbonate cage and in 2 of 12 nonchallenged mice in
      the cage with a steel mesh floor. H. pylori was detected from saliva or stool in
      two nonchallenged, infected mice in the polycarbonate cage. Moreover, RAPD
      fingerprinting using different primers of the total five strains isolated from
      five nonchallenged, infected mice in both cages showed the same pattern and
      concordance with that of the challenged strain and the strains isolated from
      challenged mice. It is demonstrated that intimate interaction is the cause of H.
      pylori transmission via saliva and stool.

PMID- 15986861
TI  - Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates aspirin
      induced gastric mucosal injury in rats.
AB  - Inhibition of type IV phosphodiesterase (PDE IV) activity reduces the production
      of various proinflammatory cytokine and suppresses neutrophil activation.
      Nonsteroidal anti-inflammatory drugs such as aspirin induce gastric mucosal
      lesions. In the pathogenesis of aspirin-induced gastric mucosal lesion, the
      contributions, of activated inflammatory cells and proinflammatory cytokine
      production are critical. The specific PDE IV inhibitor rolipram is known to be a
      potent inhibitor of inflammation by increasing intracellular cyclic AMP in
      leukocytes. The aim of the present study was to determine whether rolipram can
      ameliorate aspirin-induced gastric mucosal lesions in rats and whether the agent
      can inhibit the inrease in neutrophil accumulation and the production of
      proinflammatory cytokines. Gastric lesions were produced by administration of
      aspirin (200 mg/kg) and HCI (0.15 N; 8.0 ml/kg). Rolipram was injected 30 min
      before aspirin administration. The tissue myeloperoxidase concentration in
      gastric mucosa was measured as an indicat or of neutrophil infiltration. The
      gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) were determined by ELISA. The intragastric
      administration of aspirin induced multiple hemorrhagic erosions in rat gastric
      mucosa. Gastric mucosal lesions induced by aspirin were significantly inhibited
      by treatment with rolipram. The mucosal myeloperoxidase concentration was also
      suppressed by rolipram. Increases in the gastric content of TNF-alpha and IL
      1beta after aspirin administration were inhibited by pretreatment with rolipram.
      We demonstrated that the specific type IV PDE inhibitor, rolipram, could have a
      potent antiulcer effect, presumably mediated by its anti-inflammatory properties.

PMID- 15986862
TI  - Pancreatic and hepatic abscess secondary to fish bone perforation of the
      duodenum.

PMID- 15986863
TI  - Treatment effects of partially hydrolyzed guar gum on symptoms and quality of
      life of patients with irritable bowel syndrome. A multicenter randomized open
      trial.
AB  - The effects of partially hydrolyzed guar gum (PHGG) were compared in patients
      with irritable bowel syndrome, at 10 g/day (N = 40) and 5 g/day (N = 46) for 12
      weeks. Gastrointestinal symptoms (GSRS), quality of life (SF-36), and
      psychological symptoms (HADS) were evaluated at baseline, during treatment
      (months 1 and 3), and at follow-up (month 6). In both groups symptoms and quality
      of life improved significantly after the first month of administration until
      follow-up compared to those at baseline. However, the improvement was
      significantly reduced at follow-up compared to the end of treatment. PHGG was
      effective for improving somatic (gastrointestinal symptoms) and psychological
      (quality of life and psychological distress) symptoms over the short term. Since
      the improvement tended to decrease after the end of the treatment period, further
      studies should evaluate the benefits of PHGG at a maintenance dosage.

PMID- 15986864
TI  - Evaluation of five probiotic products for label claims by DNA extraction and
      polymerase chain reaction analysis.
AB  - Label claims were evaluated for five probiotic products. Specific oligonucleotide
      primers were designed for 11 species from the Bifidobacterium, Lactobacillus, and
      Streptococcus genera. Polymerase chain reaction, gel electrophoresis, and
      amplicon excision with DNA sequencing were performed: Sequence analysis and DNA
      homology comparisons followed. Bifidobacterium bifidum was not detected in two of
      the five samples by PCR analysis. Also, Lactobacillus species were found in two
      of the five product samples for which the species was not listed as an
      ingredient. We conclude that (1) lack of B. bifidum in two probiotic products may
      be attributed to different preparation standards among probiotic manufacturers,
      and (2) identificaition of additional Lactobacillus species may represent
      contamination of the samples related to the fact that manufacturers utilize
      shared equipment to produce all probiotics and PCR is a highly sensitive
      technique.

PMID- 15986865
TI  - Ampullary stenosis with biliary obstruction in duodenal Crohn's disease: a case
      report and review of the literature.

PMID- 15986866
TI  - Abdominal aortitis associated with Crohn's disease.

PMID- 15986867
TI  - Clostridium perfringens spontaneous bacterial peritonitis: report of a case and
      implications for management.

PMID- 15986868
TI  - Intussusception in an adult patient with mild intermittent abdominal pain.

PMID- 15986869
TI  - A clinical-morphological study on cholestatic presentation of nonalcoholic fatty
      liver disease.
AB  - To determine the association among the clinical, biochemical, and histological
      features of cholestasis, we analyzed all the relevant data of the patients
      recorded in our non-alcoholic fatty liver disease (NAFLD) database. We selected
      20 NAFLD patients with abnormal transaminase levels, with both alkaline
      phosphatase >500 U/L and gamma-glutamyl transpeptidase >250 U/L. Their
      histological features were compared with those of a group of patients with NAFLD
      matched for sex, age, and body mass index and of a group of patients matched for
      sex, body mass index and histological NAFLD grading/staging. Cases and controls
      satisfied, on histology, the criteria for NASH. The presence of cholestasis in
      our patients was correlated with injury of the bile duct epithelium,
      characterized by cholangitis, swelling, variable bile duct loss, and bile stasis.
      Compared to NAFLD patients of similar age, sex, and body mass index, the
      cholestatic group had total and severe histological liver impairment. When we
      analyzed the group of patients histologically identified on the basis of
      identical stage and grade severity, we could not find any evidence of significant
      bile damage, compared to cases, despite the control group's significantly older
      age. NAFLD patients with biochemical cholestasis have a histological picture of
      bile damage; they have more advanced histological impairment than patients
      matched for age, sex and body mass index.

PMID- 15986870
TI  - Increased orocecal transit time in patients with nonalcoholic fatty liver
      disease.
AB  - Intestinal bacterial overgrowth (IBO) has been suggested to play a pathogenic
      role in patients with nonalcoholic fatty liver disease (NAFLD). Delayed
      intestinal transit may contribute to IBO development. Ten nondiabetic patients
      with NAFLD and abnormal liver enzymes were recruited. Ten healthy individuals,
      matched by sex, age, and body mass index, were used as controls. Orocecal transit
      time (OCTT) was measured by the lactulose breath test. Anti-endotoxin core
      antibodies (EndoCAb) were determined. The effect of oral norfloxacin (400 mg BID
      during 2 weeks) on liver enzymes, lactulose breath test, and EndoCAb was also
      studied. NAFLD patients had higher basal breathed H2 and prolonged OCTT compared
      to controls (127 +/- 61 vs. 57 +/- 23 min, respectively; P = 0.0037). EndoCAb
      titers were similar in NAFLD patients and controls. Norfloxacin administration
      had no effect on ALT levels, lactulose breath test, or EndoCAb titers in patients
      with NAFLD. The present data show evidence of deranged intestinal motility in
      nondiabetic patients with NAFLD and support the hypothesis that NAFLD could be
      linked to endotoxin-induced liver damage of intestinal origin.

PMID- 15986871
TI  - High rate of seropositivity of Chlamydia pneumoniae IgA in male patients with
      nonalcoholic steatohepatitis.
AB  - The aim of this study was to investigate if there was any relationship between
      nonalcoholic steatohepatitis and the rate of Chlamydia pneumoniae seropositivity
      in a male population. Fifteen men with nonalcoholic steatohepatitis and 20
      healthy men were enrolled in the study. The seropositivity rate of Chlamydia
      pneumoniae immunoglobulin A in the nonalcoholic steatohepatitis and control
      groups was 53.3 and 5%, respectively. The rate of Chlamydia pneumoniae
      immunoglobulin A positivity was significantly higher in the nonalcoholic
      steatohepatitis group than the controls (P = 0.002), while such a difference did
      not occur for Chlamydia pneumoniae immunoglobulin G positivity (P > 0.05). There
      is an association between nonalcoholic steatohepatitis and persistent Chlamydia
      pneumoniae infection as a probable causative or triggering agent. These findings
      suggest that further studies are necessary to clarify this association.

PMID- 15986872
TI  - Dengue hemorrhagic fever and fulminant hepatic failure.

PMID- 15986874
TI  - NACA as a potential cellular target of hepatitis B virus preS1 protein.
AB  - The mechanisms of the attachment and penetration of hepatitis B virus remain
      obscure. It has been demonstrated that the preS1 region is essential for viral
      assembly and infectivity, however, as its cellular receptor has still not been
      identified unequivocally, we used a yeast two-hybrid system to screen the
      cellular proteins that can interact with preS1 protein. The protein recovered
      from a human liver cDNA library was nascent polypeptide-associated complex alpha
      polypeptide. The interaction between preS1 and nascent polypeptide-associated
      complex alpha polypeptide was verified by mating experiment and
      coimmunoprecipitation of COS7 cell lysates expressing both proteins. Based on
      these results, we speculate that nascent polypeptide-associated complex alpha
      polypeptide is a functional target of hepatitis B virus preS1 protein in cells.

PMID- 15986873
TI  - Pegylated interferon alpha-2a with or without ribavirin in HCV/HIV coinfection:
      partially blinded, randomized multicenter trial.
AB  - We evaluated the safety and efficacy of peginterferon alpha-2a (pegIFNalpha-2a),
      with or without ribavirin, in 154 HCV/HIV coinfected patients. All received
      pegIFNalpha-2a (180 microg/week) for 12 weeks, with those achieving an early
      virologic response (EVR) continued on monotherapy through week 48. Patients
      without an EVR were randomized at week 14 to also receive ribavirin (800 mg/day)
      or placebo through week 48. Patients with detectable HCV RNA at week 24 were
      discontinued. An EVR occurred in 59 of 154 patients on monotherapy, and a
      sustained virologic response (SVR) occurred in 19 of 55 of those achieving an EVR
      and continuing monotherapy through week 48. One week 12 nonresponder receiving
      pegIFNalpha-2a plus ribavirin, and none receiving pegIFNalpha-2a plus placebo,
      achieved a SVR. Discontinuations for adverse events occurred in 10 of 154
      patients before, and 16 of 131 after, week 14. HIV RNA and CD4 counts did not
      change significantly during treatment. PegIFNalpha-2a was therefore at least as
      effective as standard interferon and ribavirin combination therapy and was well
      tolerated, without a negative impact on HIV parameters.

PMID- 15986875
TI  - A preliminary study of applying chemical biliary duct embolization to chemical
      hepatectomy in rats.
AB  - The high recurrence of hepatolithiasis, together with the high operative risk of
      hepatectomy for specially located stones, has not been settled effectively to
      date. Thus, this study was designed to investigate the feasibility of applying
      chemical biliary duct embolization (CBDE) to chemical hepatectomy in rats. As
      revealed in our results, the intrahepatic biliary ducts could be partially or
      completely occluded by both phenol and absolute ethanol. In addition, the
      embolization effect was greatly enhanced by further using cyanoacrylate. Also
      noteworthy is that CBDE resulted in massive death of hepatocytes, which were
      replaced by proliferated bile ductules and collagen. More importantly, the
      hepatocytes disappeared completely in the periphery of the embolized lobe where
      chemical hepatectomy was achieved. As for the comparison of embolic agents, the
      combination of phenol and cyanoacrylate exhibited even better fibrogenic effects
      than the combination of ethanol and cyanoacrylate. In conclusion, CBDE might be a
      promising approach for achieving the effects of chemical hepatectomy. The
      combination of phenol and cyanoacrylate potentially acted as a more effective
      agent for biliary duct embolization.

PMID- 15986876
TI  - Primary neurofibroma of the common bile duct as an unusual cause of obstructive
      jaundice: a case report.

PMID- 15986877
TI  - Primary omental torsion: radiologic diagnosis in a young woman.

PMID- 15986878
TI  - Portal venous flow pattern as a useful tool for predicting esophageal varix
      bleeding in cirrhotic patients.
AB  - This study aimed to evaluate whether (1) the portal venous flow pattern
      determined by color Doppler sonography could be related to the clinical severity
      of liver cirrhosis and (2) whether the flow patterns differ between patients with
      bleeding and nonbleeding esophageal varices. One hundred twenty-nine cirrhotic
      patients and 60 noncirrhotic healthy controls were enrolled after endoscopic
      survey for the presence of esophageal varices. Each patient received color
      Doppler echography to define the pattern of blood flow direction as hepatopetal
      or nonhepatopetal (hepatofugal, turbulence, and bidirection) in type. The
      patients with esophageal varices were further categorized into two groups: with
      recent bleeding (BEV; n = 99) and without recent bleeding (NBEV; n = 30). More
      patients in the BEV group (72.7%) had a nonhepatopetal Doppler flow pattern than
      in the control group (1.7%) and NBEV group (13.3%) (P < 0.001). Among the 129
      cirrhotic patients, the nonhepatopetal flow pattern of the portal vein was higher
      in 96% of Child-Pugh grade C patients than in 41.8% of grade A patients and 57.6%
      of grade B patients (P < 0.05). Moreover, for those cirrhotic patients with Child
      Pugh grades A and B, the nonhepatopetal Doppler flow pattern was more commonly
      found in the BEV group than in the NBEV group (63.0 vs. 13.8%; odds ratio, 10.64;
      95% CI, 0.03-0.299; P < 0.001). Portal venous blood flow pattern is related to
      severity of cirrhosis. The presence of a nonhepatopetal flow pattern implicates
      an increased risk of esophageal varices bleeding, especially for those cirrhotic
      patients with Child-Pugh grades A and B.

PMID- 15986879
TI  - Extensive idiopathic colonic varices in a young patient.

PMID- 15986880
TI  - Urgent revascularization of a liver allograft with a saphenous vein interposition
      graft between the hepatic artery and the recipient splenic artery after late
      hepatic artery thrombosis.

PMID- 15986881
TI  - Gastrointestinal zygomycosis complicating heart and lung transplantation in a
      patient with Eisenmenger's syndrome.

PMID- 15986882
TI  - The amrG1 gene is involved in the activation of acetate in Corynebacterium
      glutamicum.
AB  - During growth of Corynebacterium glutamicum on acetate as its carbon and energy
      source, the expression of the pta-ack operon is induced, coding for the acetate
      activating enzymes, which are phosphotransacetylase (PTA) and acetate kinase
      (AK). By transposon rescue, we identified the two genes amrG1 and amrG2 found in
      the deregulated transposon mutant C. glutamicum G25. The amrG1 gene (NCBI
      accession: AF532964) has a size of 732 bp, encoding a polypeptide of 243 amino
      acids and apparently is partially responsible for the regulation of acetate
      metabolism in C. glutamicum. We constructed an in-frame deletion mutant and an
      over-expressing strain of amrG1 in the C. glutamicum ATCC13032 wildtype. The
      strains were then analyzed with respect to their enzyme activities of PTA and AK
      during growth on glucose, acetate and glucose or acetate alone as carbon sources.
      Compared to the parental strain, the amrG1 deletion mutant showed higher specific
      AK and PTA activities during growth on glucose but showed the same high specific
      activities of AK and PTA on medium containing acetate plus glucose and on medium
      containing acetate. In contrast to the gene deletion, overexpression of the amrG1
      gene in C. glutamicum 13032 had the adverse regulatory effect. These results
      indicate that the amrG1 gene encodes a repressor or co-repressor of the pta-ack
      operon.

PMID- 15986883
TI  - Perceptual organization at attended and unattended locations.
AB  - This study examined the effects of attention on forming perceptual units by
      proximity grouping and by uniform connectedness (UC). In Experiment 1 a row of
      three global letters defined by either proximity or UC was presented at the
      center of the visual field. Participants were asked to identify the letter in the
      middle of stimulus arrays while ignoring the flankers. The stimulus onset
      asynchrony (SOA) between stimulus arrays and masks varied between 180 and 500 ms.
      We found that responses to targets defined by proximity grouping were slower than
      to those defined by UC at median SOAs but there were no differences at short or
      long SOAs. Incongruent flankers slowed responses to targets and this flanker
      compatibility effect was larger for UC than for proximity-defined flankers.
      Experiment 2 examined the effects of spatial precueing on discrimination
      responses to proximity- and UC-defined targets. The advantage for targets defined
      by UC over targets defined by proximity grouping was greater at uncued relative
      to cued locations. The results suggest that the advantage for UC over proximity
      grouping in forming perceptual units is contingent on the stimuli not being fully
      attended, and that paying attention to the stimuli differentially benefits
      proximity grouping.

PMID- 15986884
TI  - Raman spectroscopic study on structure of human immunodeficiency virus (HIV) and
      hypericin-induced photosensitive damage of HIV.
AB  - The first Raman spectra of HIV1-HIV2 in human sera and hypericin-induced
      photosensitive damage of the virus have been obtained. The prominent Raman lines
      in the spectra are assigned respectively to the carbohydrates of viral
      glycoprotein, RNA, protein and lipid. The spectra are dominated by Raman
      scattering of the carbohydrates. The lines of D-Mannose and N-acetylglucosamine
      in carbohydrates are obvious and there is a beta-configuration in the anomeric C1
      position in D-Mannose. The viral RNA duplexes bound assumes an A-form geometry.
      The lines of backbone phosphate group, bases (involving interbase hydrogen
      bonding) and ribose of the RNA are complete and distinct. The secondary structure
      of the viral protein maintains alpha-helix, beta-sheet, beta-turn and random
      coil. Its side chains are rich and vary from tryptophan, phenylalanine and
      "buried" tyrosine; the stable conformation of the S-S bond of gauche-gauche
      gauche; the two forms of C-S bonds of gauche and trans; to sulfhydrl group and
      ionized and unionized carboxyl groups. The viral lipid bilayer molecules are
      probably in the liquid ordered phase or the gel phase. It was observed that the
      hypericin-induced photosensitive damage of HIV1-HIV2 in human sera changed
      various components of HIV1-HIV2 in different degrees: The orderly A-form viral
      RNA would become a disordered viral RNA. There were a breakage of interbase
      hydrogen bonds and disruption of vertical base-base stacking interactions. In
      addition, the groups of ribos and four bases were damaged obviously. A decrease
      in ordered structure (alpha-helix and beta-sheet) of viral protein is accompanied
      by an increase in random coil. The Tyr buried in the three-dimensional structure
      of protein was damaged, but it was still "buried" and the damage of C-S bond of
      trans form was stronger. The groups of carbohydrates, including D-Mannos and N
      acetyl glucosamine, in viral envelope glycoprotein had also been changed. The
      hydrophilic C-N bond of choline in viral lipid was damaged, which was the
      possible binding site to hypericin, whereas the viral lipids bilayers were still
      probably in the liquid ordered phase or the gel phase. So the space structure of
      HIV1-HIV2 was damaged under the experimental conditions, which might block viral
      infection and inhibit its growth and breeding. It is apparent that the laser
      Raman spectra have provided certain direct evidence at the molecular level for
      photosensitive damage of HIV1-HIV2.

PMID- 15986885
TI  - Mutations in PurBox1 of the Bacillus subtilis pur operon control site affect
      adenine-regulated expression in vivo.
AB  - Transcription of the Bacillus subtilis pur operon is regulated by a purine
      repressor (PurR)-DNA control site interaction. The pur operon control site has
      two PurBoxes that are required for high-affinity PurR binding. An upstream,
      strong-binding PurBox1 is at position -81 to -68 relative to the transcription
      start site and a downstream weak-binding PurBox2 is at position -49 to -36. We
      constructed three PurBox1 mutations and the effects on binding of PurR to the
      control region in vitro and on regulation of pur operon expression in vivo were
      investigated. The mutations significantly reduced the binding of PurR to control
      region DNA. In strains with G-75A, G-75T and a five bp deletion (delta5) pur
      operon repression was defective in vivo. In addition in vivo PurR titration was
      used to confirm that sequences flanking PurBox1 and PurBox2 are required for PurR
      binding to the puroperon control site.

PMID- 15986886
TI  - Thermostability of photosynthesis in two new chlorophyll b-less rice mutants.
AB  - Leaves of the two new chlorophyll b-less rice mutants VG28-1, VG30-5 and the wild
      type rice cv. Zhonghua 11 were subjected to temperatures 28, 36, 40, 44 and 48
      degrees C in the dark for 30 min or gradually elevated temperature from 30
      degrees C to 80 degrees C at 0.5 degrees C/min. The thermostability of
      photosynthetic apparatus was estimated by the changes in chlorophyll fluorescence
      parameters, photosynthetic rate and pigment content, chloroplast ultrastructure
      and tissue location of H2O2 accumulation. There were different patterns of F(o)
      temperature curves between the Chl b-less mutants and the wild type plant, and
      the temperature of F(o) rising threshold was shifted 3 degrees C lower in the Chl
      b-less mutants (48 degrees C) than in the wild type (51 degrees C). At
      temperature up to about 45 degrees C, chloroplasts were swollen and thylakoid
      grana became misty accompanied with the complete loss of photosynthetic oxygen
      evolution in the two Chl b-less mutants, but chloroplast ultrastructure in the
      wild type showed no obvious alteration. After 55 degrees C exposure, the
      disordered thylakoid and significant H2O2 accumulation in leaves were found in
      the two Chl b-less mutants, whereas in the wild type plant, less H2O2 was
      accumulated and the swollen thylakoid still maintained a certain extent of
      stacking. A large extent of the changes in qP, NPQ and Fv/Fm was consistent with
      the Pn decreasing rate in the Chl b-less mutants during high temperature
      treatment as compared with the wild type. The results indicated that the Chl b
      less mutants showed a tendency for higher thermosensitivity, and loss of Chl b in
      LHC II could lead to less thermostability of PSII structure and function. Heat
      damage to photosynthetic apparatus might be partially attributed to the internal
      oxidative stress produced at severely high temperature.

PMID- 15986887
TI  - Role of trichome of Pteris vittata L. in arsenic hyperaccumulation.
AB  - Environmental scanning electron microscope (ESEM) fitted with an energy
      dispersive X-ray microanalyzer (EDX) was used to investigate the surface
      micromorphology and arsenic (As) micro-distribution in Chinese brake (Pteris
      vittata L.). It was found that amounts of trichome, which possessed multicellular
      structure with the average length of 160 microm and with an average diameter of
      28 microm, existed in the frond of P. vittata, and the density of trichome on the
      pinnate axial surface was higher than that on the petiole. Visible X-ray peak of
      As was recorded in the epidermal cell and trichome. The relative weight of As in
      the pinnate trichome, which contained the highest concentration of As among all
      tissues of the plant, was 2.4 and 3.9 times as much as that in the epidermal and
      mesophyllous cells, respectively. The As concentrations in the basal and stalk
      cells of the same trichome were higher than that in its cap cell. This is the
      first time to report that the trichome of P. vittata plays an important role in
      arsenic hyperaccumulation. The finding from the present study implies that much
      attention should be paid to the role of the trichome in understanding the
      hyperaccumulation and detoxicity of As in the hyperaccumulator and improving the
      ability of As accumulation.

PMID- 15986888
TI  - Monitoring of microbial community structure and succession in the biohydrogen
      production reactor by denaturing gradient gel electrophoresis (DGGE).
AB  - To study the structure of microbial communities in the biological hydrogen
      production reactor and determine the ecological function of hydrogen producing
      bacteria, anaerobic sludge was obtained from the continuous stirred tank reactor
      (CSTR) in different periods of time, and the diversity and dynamics of microbial
      communities were investigated by denaturing gradient gel electrophoresis (DGGE).
      The results of DGGE demonstrated that an obvious shift of microbial population
      happened from the beginning of star-up to the 28th day, and the ethanol type
      fermentation was established. After 28 days the structure of microbial community
      became stable, and the climax community was formed. Comparative analysis of 16S
      rDNA sequences from reamplifying and sequencing the prominent bands indicated
      that the dominant population belonged to low G+C Gram-positive bacteria
      (Clostridium sp. and Ethanologenbacterium sp.), beta-proteobacteria (Acidovorax
      sp.), gamma-proteobacteria (Kluyvera sp.), Bacteroides (uncultured bacterium SJA
      168), and Spirochaetes (uncultured eubacterium E1-K13), respectively. The
      hydrogen production rate increased obviously with the increase of
      Ethanologenbacterium sp., Clostridium sp. and uncultured Spirochaetes after 21
      days, meanwhile the succession of ethanol type fermentation was formed.
      Throughout the succession the microbial diversity increased however it decreased
      after 21 days. Some types of Clostridium sp. Acidovorax sp., Kluyvera sp., and
      Bacteroides were dominant populations during all periods of time. These special
      populations were essential for the construction of climax community. Hydrogen
      production efficiency was dependent on both hydrogen producing bacteria and other
      populations. It implied that the co-metabolism of microbial community played a
      great role of biohydrogen production in the reactors.

PMID- 15986889
TI  - Structural basis of interaction between protein tyrosine phosphatase PCP-2 and
      beta-catenin.
AB  - PCP-2 is a member of receptor-like protein tyrosine phosphatase of the MAM domain
      family. To investigate which part of PCP-2 was involved in its interaction with
      beta-catenin, we constructed various deletion mutants of PCP-2. These PCP-2
      mutants and wild-type PCP-2 were co-transfected into BHK-21 cells with beta
      catenin individually. An in vivo binding assay revealed that the expression of
      wild-type PCP-2, PCP-2 deltaC1C2 (deleted PCP-2 without both PTP domains) and PCP
      2 deltaC2 (deleted PCP-2 without the second PTP domain) could be
      immunoprecipitated by anti-catenin antibody in every co-transfection, but PCP-2
      EXT (deleted PCP-2 without the juxtamembrane region and both PTP domains) was
      missing, which implied that PCP-2 and beta-catenin could associate directly and
      the juxtamembrane region in PCP-2 was sufficient for the process.

PMID- 15986890
TI  - Comparative analysis of the pig BAC sequence involved in the regulation of
      myostatin gene.
AB  - Myostatin (GDF8, MSTN) is a member of the transforming growth factor beta
      superfamily that is essential for proper regulation of skeletal muscle mass. In
      order to study its expression and regulatory mechanism deeply, we have presented
      a comparative analysis of about 170-kb pig BAC sequence containing the myostatin
      gene among pig, human and mouse. The genomic region is characterized by high
      interspersed repeats and low G+C content. As for the myostatin gene, a higher
      sequence similarity is found between human and pig than between these species and
      the mouse. One striking feature is that the structure of two TATA-boxes in the
      nearby downstream of CCAAT-box is identified in the promoter. Further analysis
      reveals that the TATA-box1 is responsible for the transcription in pig and human,
      but the TATA-box2 acts on the transcription in mouse. The other interesting
      feature is that two polyadenylation signal sequences (AATAAA) exist in 3'UTR of
      the pig myostatin gene. Moreover, a large number of potential transcription
      factor-binding sites are also identified in evolutionary conserved regions
      (ECRs), which may be associated with the regulation of myostatin. Many putative
      transcription factors play an important role in the muscle development, and the
      complex interaction between myostatin and these factors may be required for
      proper muscle development.

PMID- 15986891
TI  - DGP1, a drought-induced guard cell-specific promoter and its function analysis in
      tobacco plants.
AB  - The genetic regulation of stomatal movement mainly depends on an efficient
      control system of gene expression, and guard cell-specific promoter is becoming
      the best choice. Here we combined the dehydration responsive element (DRE) with
      guard cell specific element (GCSE) to construct a novel promoter, DGP1.
      Histochemical assays in transgenic tobacco carrying beta, -glucuronidase (gus)
      gene fused to DGP1 demonstrated that GUS activity was found to be highly
      inducible by drought treatment and specifically restricted to guard cells. No GUS
      activity was detected in roots, stems or flowers after treatment. Further
      quantitative analysis showed that GUS activity in the epidermal strips was
      apparently induced by dehydration and dramatically increased with the elongation
      of treatment. The GUS activity after 8 h treatment was 179 times that of those
      without treatment. Although GUS activity in roots, stems or mesophyll increased
      after treatment, no great changes were observed. These results suggested that
      DGP1 could drive target gene expressed in guard cells when plant is subjected to
      drought stress. And this gets us prepared to control opening and closing of
      stomata through plant gene engineering.

PMID- 15986893
TI  - Ear plug article failed the test.

PMID- 15986892
TI  - Insulin-like growth factor 2 as a candidate gene influencing growth and carcass
      traits and its bialleleic expression in chicken.
AB  - We have identified DNA polymorphisms in the gene of insulin-like growth factor 2
      by PCR-SSCP in a resource population, which was generated by Silky reciprocally
      crossing to Broilers. A C --> G mutation was detected in the exon 2 (at position
      71) by sequencing. This single nucleotide polymorphism (SNP) was found to be
      associated with production traits. Chicken with BB genotype showed more chest
      angle width but less 3 week body weight and glandular stomach weight than chicken
      with AA genotype (P < 0.05); while the heterozygote (AB genotype) chicken had
      more abdominal fat weight, eviscerated yield with giblet than AA homozygote
      chicken. Further analysis showed that there were different genetic effects on
      some traits between heterozygote AB (paternal allele given first) and
      heterozygote BA: chickens with genotype BA had more birth weight and breast
      weight but less abdominal fat weight than chickens with genotype AB (P < 0.05),
      which could be hypothetically contributed by genome imprinting. Therefore, Silky
      chickens were selected for production of heterozygotes to confirm whether IGF2
      locus was imprinting. Progeny from heterozygote x homozygote reciprocal cross was
      assayed for expression after the genotype was determined. The transcription of
      IGF2 was detected by RT-PCR-SSCP. IGF2 gene was expressed bialleleically in 1-day
      old neonatal liver and 90-day-old liver, kidney, heart, and muscle of both
      heterozygote AB and BA chickens. Therefore, IGF2 was not an imprinting gene in
      chicken. The different genetic effects between the heterozygote AB and BA remain
      to be elucidated.

PMID- 15986894
TI  - Employers must be alert to comp fraud.

PMID- 15986895
TI  - AIHA's local sections.

PMID- 15986896
TI  - Avoid these 10 mistakes.

PMID- 15986897
TI  - Preventing chlorine gas accidents.

PMID- 15986898
TI  - Understanding oxygen sensor performance.

PMID- 15986899
TI  - I think it's mold! (Now what?).

PMID- 15986900
TI  - Our magnificent workplace obsession.

PMID- 15986901
TI  - Conditioning the air.

PMID- 15986902
TI  - Disposable particle masks.

PMID- 15986903
TI  - Accident victims are more than statistics.

PMID- 15986904
TI  - Tracking down a killer.

PMID- 15986905
TI  - Higher capabilities for safety-rated control circuits.

PMID- 15986907
TI  - Dealing with personal communication in the workplace--what's your policy?

PMID- 15986906
TI  - Rebuilding East Timor--what is an Australian vet up to?

PMID- 15986908
TI  - AVA great debate: 'real vets are men'!

PMID- 15986909
TI  - Anal sac tumours of the dog and their response to cytoreductive surgery and
      chemotherapy.
AB  - A retrospective study of anal sac tumours without pulmonary metastases, from the
      author's clinical records for the period July 1989 to July 2002, was conducted to
      establish the response to treatment with surgery and melphalan chemotherapy. Of
      21 dogs with tumours of the anal sacs 19 had apocrine gland adenocarcinomas of
      anal sac origin, one had a benign papillary cystadenoma and another had a
      malignant melanoma. Two of the 19 dogs had bilateral anal sac adenocarcinomas.
      Ten of the 19 dogs with apocrine gland adenocarcinomas of anal sac origin had
      sublumbar lymphadenopathy. Five dogs were excluded by their owners from
      recommended treatment. Fourteen dogs with apocrine gland adenocarcinomas of anal
      sac origin were treated by surgical cytoreduction and chemotherapy with
      melphalan. Seven of the 14 dogs had regional lymph node metastases. Cytoreduction
      was by local excision of the anal sac in all 14 dogs and concurrent removal of
      the sublumbar retroperitoneal lymph nodes in the seven dogs with regional lymph
      node metastases. The median survival time of dogs with sublumbar nodal metastasis
      was 20 months and for dogs with tumour localised to the anal sac the median
      survival time was 29.3 months. There was no difference in median survival of
      those dogs with sublumbar metastases compared to those without. This study
      suggests there is a role for melphalan in the treatment of dogs with anal sac
      adenocarcinoma when combined with cytoreductive surgery, with treatment survival
      times and the local recurrence rate of the primary tumour comparing favourably
      with previously published treatment regimes.

PMID- 15986910
TI  - Seasonal infertility in large pig production units in an Eastern-European
      climate.
AB  - OBJECTIVES: To demonstrate the occurrence of seasonal infertility of sows in
      large production units in Eastern Europe. DESIGN: Weaners in this trial
      originated from a 1000 sow Croatian herd that weaned piglets at 14 or 28 days of
      age. The production records of 15 indoor (795 to 1849 sows per herd) pig farms
      with identical feeding, similar genetics and health status, were evaluated. The
      reproductive performance of sows when the average daily (9 am to 4 pm)
      temperature was more than 35 degrees C, was compared with the weeks when it was
      lower than 30 degrees C. RESULTS: During periods of high temperature (> 35
      degrees C) sows had significantly (P < or = 0.05) longer weaning to service
      intervals and more regular returns to service (P < or = 0.05) compared to weeks
      of less than 30 degrees C daily temperature in the same summer season. Irregular
      returns to service were low and showed no significant differences during the same
      time periods. Farrowing rates and total litter sizes were lower (P < or = 0.05)
      for periods of higher than 35 degrees C daily temperature compared to weeks of
      less than 30 degrees C daily temperature in the same summer season. CONCLUSION:
      When daily temperatures are higher than 35 degrees C, reproductive performance is
      likely to be depressed in large pig production units.

PMID- 15986911
TI  - Clinical acidosis in a Gippsland dairy herd.
AB  - OBJECTIVE: To report on spontaneous clinical and subclinical acidosis in a large
      dairy herd, to evaluate the diets and feeding strategies involved, and to report
      on measures of rumen function in the cows affected. DESIGN: A Gippsland dairy
      herd was sampled as part of a wider randomised cross-sectional study that
      examined the prevalence, risk factors for, and effects of, acidosis on rumen
      function of dairy cattle. Three herds on the farm were involved in the study: the
      transition herd (cows 3 weeks prior to calving), the very fresh lactating herd (1
      < days in milk < 10, herd 1) and the fresh lactating herd (10 < days in milk <
      120, herd 2) including a small lame herd fed separately. The transition cows were
      fed 2 kg dry matter triticale per cow per day and hay with an estimated total dry
      matter intake of 4.8 kg per cow per day. The lactating cow diet included 6.75 kg
      dry matter triticale per cow per day with total concentrate fed being 8.1 kg dry
      matter per cow per day in the milking parlour. Silage, lucerne cubes, hay and
      pasture (herd 2 only) was also fed to the lactating cows with the estimated total
      dry matter intake for cows in herds 1 and 2 being 13.7 kg and 20.8 kg per cow per
      day respectively. Three primiparous and five multiparous cows in early lactation
      (< 100 days in milk) were randomly selected from each of two lactating herds:
      herds 1 and 2. Rumen fluid was sampled from each cow by both rumenocentesis and
      stomach tube. The rumenocentesis samples were tested for pH at the time of
      sampling. Stomach tube samples were frozen and subsequently tested for volatile
      fatty acid, ammonia, and D- and L-lactate concentration. RESULTS: In the very
      fresh herd, there was a high prevalence of severe lameness and scouring, coupled
      with a mean rumen pH 5.67, low mean total volatile fatty acid concentration 71.0
      mM and high mean concentrations of L- and D-lactate, (7.71 mM and 7.31 mM),
      respectively. Cows in the fresh herd had moderate signs of scouring and lameness.
      A lame herd comprising approximately 50 cows separated from the fresh herd was
      also present on the farm. The mean rumen pH of the fresh herd was 5.74 and mean
      rumen concentrations of volatile fatty acids, ammonia, L- and D-lactate were
      within ranges considered normal. CONCLUSIONS: The transition diet failed to
      supply sufficient energy and protein for maintenance of cows of this live weight
      in late gestation. The diet fed to the very fresh herd was low in effective fibre
      and contained an excessive content of non-structural carbohydrate in the form of
      processed, rapidly fermentable grain. The sudden change from the transition diet
      to the diet fed to the very fresh herd probably also precipitated the outbreak of
      acidosis. This case report provides unique detail, including information on diets
      and rumen parameters, of an outbreak of acidosis in a pasture-fed herd.

PMID- 15986912
TI  - Australian tick paralysis in a dog imported into the UK.

PMID- 15986913
TI  - Microfilaraemia associated with Pelecitus roemeri in a western grey kangaroo
      (Macropus fuliginosus).

PMID- 15986914
TI  - Continuing professional development for veterinarians.

PMID- 15986915
TI  - Prevalence of serum antibodies to canine adenovirus and canine herpesvirus in the
      European red fox (Vulpes vulpes) in Australia.
AB  - OBJECTIVES: To determine the seroprevalence and aspects of the epidemiology of
      canine adenovirus (CAdV) and canine herpesvirus (CaHV-1) in European red foxes
      (Vulpes vulpes) in Australia. DESIGN: Serum samples were collected
      opportunistically from foxes in 1991-1994 in Western Australia (WA) and South
      Australia (SA) and in 1980-1984 and 1990-1994 in New South Wales (NSW) and the
      Australian Capital Territory (ACT). The sera were examined for antibody to CAdV
      and CaHV-1 using ELISAs. Seroprevalence in the different regions was determined
      for both viruses and the CAdV data were analysed for interactions between decade
      of collection, age, season, region and gender using logistic regression. RESULTS:
      The overall prevalence of antibody to CAdV was 23.2% (308/1326) but was
      significantly higher in sera collected in the eastern states of Australia (47%:
      233/498) than in WA (9%: 75/828). Overall, in NSW and the ACT, there was a
      significantly lower prevalence in juveniles than in adults and the prevalence in
      juveniles in the 1990s was significantly lower than in the 1980s. The prevalence
      was also significantly lower in the autumn than in the winter for juveniles but
      the reverse held for adults. The NSW and ACT data were subdivided into eastern
      (including the ACT) and western regions. This revealed a significantly higher
      prevalence in the winter than in the autumn for the west and the reverse in the
      east. In WA, the northern rangeland regions of WA had lower prevalence (1.9%)
      than the southern agriculture regions (10.7%). Seasonally, there was a peak
      prevalence in the spring dropping through the summer and autumn and rising again
      in the winter. This seasonal pattern was also found in the combined data for all
      sites in the 1990s. There was no gender difference in prevalence of CAdV either
      overall or in different regions. The overall prevalence of antibody to CaHV-1 was
      2.2% (28/1300). The small number of positives allowed only limited statistical
      analysis that did not reveal any differences in decade of collection, age, season
      or region. CONCLUSIONS: CAdV infection is common in the Australian fox population
      whereas CaHV-1 infection is rare. For CAdV, the age and seasonal patterns of
      seroprevalence were generally consistent with the recruitment of young
      susceptible foxes into the population in the spring and the accumulation of
      infections with age. The differences in regional prevalences correlated with fox
      density. The low prevalence of antibody to CaHV-1 suggests that CaHV-1 may be a
      more suitable vector than CAdV for bait delivery of immunocontraceptive antigens
      to foxes in Australia.

PMID- 15986916
TI  - Acute post-parturient haemoglobinuria in dairy cows and phosphorus status.
AB  - During the conduct of an experiment designed to examine the nutritional
      management of dairy cows in late pregnancy, four cows out of 72 suffered from
      acute haemoglobinuria two to four weeks after calving. Thirty-six thin and 36 fat
      cows were individually fed one of three diets based on a total mixed ration with
      different energy or protein concentrations during the last 3 to 4 weeks before
      expected calving date. After calving, cows grazed pasture and were offered 6 kg
      dry matter of pelleted concentrates daily. The P concentrations of the feeds
      offered suggested that the cows' diets were marginally deficient in P relative to
      requirements. Plasma P concentrations were significantly (P < 0.05) lower in fat
      cows than in thin cows during the first 6 weeks of lactation (0.87 versus 1.12
      mmol/L), but precalving diet had no effect (P > 0.05). Concentrations of plasma
      inorganic P of the four fat cows that developed acute haemoglobinuria were less
      than 0.3 mmol/L. However, plasma P concentrations in another 12 cows, none of
      which displayed overt symptoms, declined to similar levels. It appeared that
      inadequate dietary P may have predisposed cows to acute haemoglobinuria, but the
      precipitating cause was not readily obvious.

PMID- 15986917
TI  - Femoral asymmetry in the Thoroughbred racehorse.
AB  - OBJECTIVE: To investigate the occurrence of geometrical asymmetries in the macro
      architecture of left and right femurs from Thoroughbred racehorses previously
      used in competitive training and racing in New South Wales, Australia. METHODS:
      Detailed postmortem measurements were made of 37 characteristics of left and
      right femurs from eleven Thoroughbred racehorses euthanased for reasons unrelated
      to the study. Measurements focused on articulating surfaces and sites of
      attachment of muscles and ligaments known to be associated with hindlimb
      locomotion. RESULTS: Five measurements were significantly larger in left compared
      to right femurs (P < 0.05). The regions showing significant differences between
      left and right limbs were proximal cranial and overhead medio-lateral widths,
      greater trochanter depth, depth of the fovea in the femoral head and distal inter
      epicondylar width. CONCLUSION: The left-right differences in femoral morphology
      were associated with sites of muscle and ligament attachment known to be involved
      with hindlimb function in negotiating turns. These differences may be the result
      of selection pressure for racing performance on curved race tracks and/or
      adaptations related to asymmetrical loading of the outside hindlimb associated
      with repeated negotiation of turns on such tracks.

PMID- 15986918
TI  - Drying times of umbilical cords of dairy calves.
AB  - OBJECTIVE: To determine the distribution of drying times of umbilical cords of
      dairy calves and to determine if cord dryness is a reliable indicator of age.
      DESIGN: An observational study was undertaken in a spring calving herd in
      Victoria, of the umbilical cords of 188 calves (82 Friesian bulls, 82 Friesian
      heifers, 24 crossbreds). PROCEDURE: Umbilical cords were examined daily, visually
      and by palpation, until the cord to the junction of the skin on the abdomen of
      the calf was dry, shrivelled and inflexible. RESULTS: Drying times ranged from 1
      to 8 days. By the fifth day of life, the umbilical cords of 96.7% of all calves,
      97.5% Friesian heifer calves, 87.5% of Friesian bull calves and 100% of cross
      bred calves were dry. If cord dryness only was used to select calves for sale,
      91.3% of all calves, 86.4% of Friesian bull calves and 100% of cross bred calves
      could have been sold before their fifth day of life. If calves were selected on
      age only, 3.3% of all calves, 2.5% of Friesian heifer calves and 12.5% of
      Friesian bull calves would have been sold before their umbilical cord was dry.
      CONCLUSION: The dairy industry cannot rely on cord dryness alone as an indicator
      of age for selection of calves for sale and transportation. Cord dryness is a
      poor indicator of age.

PMID- 15986919
TI  - Knemidocoptes intermedius in wild superb lyrebirds (Menura novaehallandiae).

PMID- 15986920
TI  - Overexpression of a rice NPR1 homolog leads to constitutive activation of defense
      response and hypersensitivity to light.
AB  - Arabidopsis NPR1/NIM1 is a key regulator of systemic acquired resistance (SAR),
      which confers lasting broad-spectrum resistance. Previous reports indicate that
      rice has a disease-resistance pathway similar to the Arabidopsis SAR pathway.
      Here we report the isolation and characterization of a rice NPR1 homologue (NH1).
      Transgenic rice plants overexpressing NH1 (NH1ox) acquire high levels of
      resistance to Xanthomonas oryzae pv. oryzae. The resistance phenotype is
      heritable and correlates with the presence of the transgene and reduced bacterial
      growth. Northern analysis shows that NH1ox rice spontaneously activates defense
      genes, contrasting with NPR1-overexpressing Arabidopsis, where defense genes are
      not activated until induction. Wild-type NH1, but not a point mutant
      corresponding to npr1-1, interacts strongly with the rice transcription factor
      rTGA2.2 in yeast two-hybrid. Greenhouse-grown NH1ox plants develop lesion-mimic
      spots on leaves at preflowering stage although no other developmental effects are
      observed. However, when grown in growth chambers (GCs) under low light, NH1ox
      plants are dwarfed, indicating elevated sensitivity to light. The GC-grown NH1ox
      plants show much higher salicylic acid (SA) levels than the wild type, whereas
      greenhouse-grown NH1ox plants contain lower SA. These results indicate that NH1
      may be involved in the regulation of SA in response to environmental changes.

PMID- 15986921
TI  - The LATD gene of Medicago truncatula is required for both nodule and root
      development.
AB  - The evolutionary origins of legume root nodules are largely unknown. We have
      identified a gene, LATD, of the model legume Medicago truncatula, that is
      required for both nodule and root development, suggesting that these two
      developmental processes may share a common evolutionary origin. The latd mutant
      plants initiate nodule formation but do not complete it, resulting in immature,
      non-nitrogen-fixing nodules. Similarly, lateral roots initiate, but remain short
      stumps. The primary root, which initially appears to be wild type, gradually
      ceases growth and forms an abnormal tip that resembles that of the mutant lateral
      roots. Infection by the rhizobial partner, Sinorhizobium meliloti, can occur,
      although infection is rarely completed. Once inside latd mutant nodules, S.
      meliloti fails to express rhizobial genes associated with the developmental
      transition from free-living bacterium to endosymbiont, such as bacA and nex38.
      The infecting rhizobia also fail to express nifH and fix nitrogen. Thus, both
      plant and bacterial development are blocked in latd mutant roots. Based on the
      latd mutant phenotype, we propose that the wild-type function of the LATD gene is
      to maintain root meristems. The strong requirement of both nodules and lateral
      roots for wild-type LATD gene function supports lateral roots as a possible
      evolutionary origin for legume nodules.

PMID- 15986922
TI  - Role of cellulose fibrils and exopolysaccharides of Rhizobium leguminosarum in
      attachment to and infection of Vicia sativa root hairs.
AB  - Infection and subsequent nodulation of legume host plants by the root nodule
      symbiote Rhizobium leguminosarum usually require attachment of the bacteria to
      root-hair tips. Bacterial cellulose fibrils have been shown to be involved in
      this attachment process but appeared not to be essential for successful
      nodulation. Detailed analysis of Vicia sativa root-hair infection by wild-type
      Rhizobium leguminosarum RBL5523 and its cellulose fibril-deficient celE mutant
      showed that wild-type bacteria infected elongated growing root hairs, whereas
      cellulose-deficient bacteria infected young emerging root hairs.
      Exopolysaccharide-deficient strains that retained the ability to produce
      cellulose fibrils could also infect elongated root hairs but infection thread
      colonization was defective. Cellulose-mediated agglutination of these bacteria in
      the root-hair curl appeared to prevent entry into the induced infection thread.
      Infection experiments with V sativa roots and an extracellular polysaccharide
      (EPS)- and cellulose-deficient double mutant showed that cellulose-mediated
      agglutination of the EPS-deficient bacteria in the infection thread was now
      abolished and that infection thread colonization was partially restored.
      Interestingly, in this case, infection threads were initiated in root hairs that
      originated from the cortical cell layers of the root and not in epidermal root
      hairs. Apparently, surface polysaccharides of R. leguminosarum, such as cellulose
      fibrils, are determining factors for infection of different developmental stages
      of root hairs.

PMID- 15986923
TI  - RNA silencing of mycotoxin production in Aspergillus and Fusarium species.
AB  - Mycotoxins are natural fungal products that are defined by their harmful effects
      on humans and animals. Aflatoxin contamination of maize by Aspergillus species
      and trichothecene contamination of small grains by Fusarium species are two of
      the most severe mycotoxin problems in the United States. We are investigating RNA
      silencing in an effort to identify novel ways to control mycotoxin contamination
      of crops. Transformation of two Aspergilli (A. flavus and A. parasiticus) and a
      Fusarium (F. graminearum) with inverted repeat transgenes (IRT) containing
      sequences of mycotoxin-specific regulatory genes suppressed mycotoxin production
      in all three plant-pathogenic fungi. This atoxigenic phenotype was stable during
      infection on corn and wheat, and importantly, F. graminearum IRT strains were
      less virulent on wheat than were wild type. The IRT did not alter physiological
      characteristics of the fungi, such as spore production and growth rate on solid
      media. These results indicate that RNA silencing exists in Aspergillus and
      Fusarium plant pathogens and suggest that RNA silencing technology may be a
      useful tool for eliminating mycotoxin contamination of agricultural products.

PMID- 15986924
TI  - Characterization of the hrpF pathogenicity peninsula of Xanthomonas oryzae pv.
      oryzae.
AB  - The hrp gene cluster of Xanthomonas spp. contains genes for the assembly and
      function of a type III secretion system (TTSS). The hrpF genes reside in a region
      between hpaB and the right end of the hrp cluster. The region of the hrpF gene of
      Xanthomonas oryzae pv. oryzae is bounded by two IS elements and also contains a
      homolog of hpaF of X. campestris pv. vesicatoria and two newly identified genes,
      hpa3 and hpa4. A comparison of the hrp gene clusters of different species of
      Xanthomonas revealed that the hrpF region is a constant yet more variable
      peninsula of the hrp pathogenicity island. Mutations in hpaF, hpa3, and hpa4 had
      no effect on virulence, whereas hrpF mutants were severely reduced in virulence
      on susceptible rice cultivars. The hrpF genes from X. campestris pv. vesicatoria,
      X. campestris pv. campestris, and X. axonopodis pv. citri each were capable of
      restoring virulence to the hrpF mutant of X. oryzae pv. oryzae. Correspondingly,
      none of the Xanthomonas pathovars with hrpF from X. oryzae pv. oryzae elicited a
      hypersensitive reaction in their respective hosts. Therefore, no evidence was
      found for hrpF as a host-specialization factor. In contrast to the loss of Bs3
      dependent reactions by hrpF mutants of X. campestris pv. vesicatoria, hrpF
      mutants of X. oryzae pv. oryzae with either avrXa10 or avrXa7 elicited
      hypersensitive reactions in rice cultivars with the corresponding R genes. A
      double hrpFxoo-hpa1 mutant also elicited an Xa10-dependent resistance reaction.
      Thus, loss of hrpF, hpal, or both may reduce delivery or effectiveness of type
      III effectors. However, the mutations did not completely prevent the delivery of
      effectors from X. oryzae pv. oryzae into the host cells.

PMID- 15986925
TI  - Induction of resistance to Verticillium dahliae in Arabidopsis thaliana by the
      biocontrol agent K-165 and pathogenesis-related proteins gene expression.
AB  - The biocontrol bacterium Paenibacillus alvei K165 has the ability to protect
      Arabidopsis thaliana against Verticillium dahliae. A direct antagonistic action
      of strain K165 against V. dahliae was ruled out, making it likely that K165
      mediated protection results from induced systemic resistance (ISR) in the host.
      K165-mediated protection was tested in various Arabidopsis mutants and transgenic
      plants impaired in defense signaling pathways, including NahG (transgenic line
      degrading salicylic acid [SA]), etr1-1 (insensitive to ethylene), jar1-1
      (insensitive to jasmonate), npr1-1 (nonexpressing NPR1 protein), pad3-1
      (phytoalexin deficient), pad4-1 (phytoalexin deficient), eds5/sid1 (enhanced
      disease susceptibility), and sid2 (SA-induction deficient). ISR was blocked in
      Arabidopsis mutants npr1-1, eds5/sid1, and sid2, indicating that components of
      the pathway from isochorismate and a functional NPR1 play a crucial role in the
      K165-mediated ISR. Furthermore, the concomitant activation and increased
      transient accumulation of the PR-1, PR-2, and PR-5 genes were observed in the
      treatment in which both the inducing bacterial strain and the challenging
      pathogen were present in the rhizosphere of the A. thaliana plants.

PMID- 15986927
TI  - Autoactive alleles of the flax L6 rust resistance gene induce non-race-specific
      rust resistance associated with the hypersensitive response.
AB  - L6 is a nucleotide binding site-leucine rich repeat (NBS-LRR) gene that confers
      race-specific resistance in flax (Linum usitatissimum) to strains of flax rust
      (Melampsora lini) that carry avirulence alleles of the AvrL567 gene but not to
      rust strains that carry only the virulence allele. Several mutant and recombinant
      forms of L6 were made that altered either the methionine-histidine-aspartate
      (MHD) motif conserved in the NBS domain of resistance proteins or exchanged the
      short domain C-terminal to the LRR region that is highly variable among L allele
      products. In transgenic flax some of these alleles are autoactive; they cause a
      gene dosage-dependent dwarf phenotype and constitutive expression of genes that
      are markers for the plant defense response. Their effects and penetrance ranged
      from extreme to mild in their degree of plant stunting, survival, and
      reproduction. Dwarf plants were also resistant to flax rust strains virulent to
      wild-type L6 plants, and this nonspecific resistance was associated with a
      hypersensitive response (HR) at the site of rust infection. The strongest
      autoactive allele, expressed in Arabidopsis from an ethanol-inducible promoter,
      gave rise to plant death dependent on the enhanced disease susceptibility 1
      (EDS1) gene, which indicates that the mutant flax (Linaceae) L6 gene can signal
      cell death through a defined disease-resistance pathway in a different plant
      family (Brassicaceae).

PMID- 15986926
TI  - Isolation of an N-alkylated benzylamine derivative from Pseudomonas putida BTP1
      as elicitor of induced systemic resistance in bean.
AB  - Root treatment of Phaseolus vulgaris with the nonpathogenic Pseudomonas putida
      BTP1 led to significant reduction of the disease caused by the pathogen Botrytis
      cinerea on leaves. The molecular determinant of P. putida BTP1 mainly responsible
      for the induced systemic resistance (ISR) was isolated from cell-free culture
      fluid after growth of the strain in the iron-poor casamino acid medium. Mass
      spectrometry analyses performed on both the bacterial product and synthetic
      analogues revealed a polyalkylated benzylamine structure, with the quaternary
      ammonium substituted by methyl, ethyl, and C13 aliphatic groups responsible for
      the relative hydrophobicity of the molecule. The specific involvement of the N
      alkylated benzylamine derivative (NABD) in ISR elicitation was first evidenced by
      testing the purified compound that mimicked the protective effect afforded by
      crude supernatant samples. The evidence was supported by the loss of elicitor
      activity of mutants impaired in NABD biosynthesis. Our experiments also showed
      that other iron-regulated metabolites secreted by the strain are not involved in
      ISR stimulation. Thus, these results indicate a wider variety of Pseudomonas
      determinants for ISR than reported to date.

PMID- 15986928
TI  - Identification of arabidopsis loci required for susceptibility to the downy
      mildew pathogen Hyaloperonospora parasitica.
AB  - Plants are susceptible to a limited number of pathogens. Most infections fail due
      to active defense or absence of compatibility. Many components of the plant's
      surveillance system and defense arsenal have been identified in the last decades.
      However, knowledge is limited on compatibility; in particular, the role of plant
      factors in the infection process. To gain insight into these processes, we have
      initiated an Arabidopsis thaliana mutant screen for reduced susceptibility to the
      downy mildew pathogen Hyaloperonospora parasitica. Ethyl methane sulfonate (EMS)
      mutants were generated in the highly susceptible Arabidopsis line Ler eds1-2.
      Eight downy mildew-resistant (dmr) mutants were analyzed in detail, corresponding
      to six different loci. Microscopic analysis showed that, in all mutants, H.
      parasitica growth was severely reduced. Resistance of dmr3, dmr4, and dmr5 was
      associated with constitutive expression of PR-1. Furthermore, dmr3 and dmr4, but
      not dmr5, also were resistant to Pseudomonas syringae and Golovinomyces orontii,
      respectively. However, enhanced activation of plant defense was not observed in
      dmr1, dmr2, and dmr6. We postulate that, in these susceptibility mutants,
      cellular processes are disrupted which are required for H. parasitica infection.
      This interesting new set of mutants provides a basis to elucidate the molecular
      processes underlying susceptibility to downy mildew in Arabidopsis.

PMID- 15986929
TI  - Selection of Heterodera glycines chorismate mutase-1 alleles on nematode
      resistant soybean.
AB  - The soybean cyst nematode Heterodera glycines is the most destructive pathogen of
      soybean in the Unites States. Diversity in the parasitic ability of the nematode
      allows it to reproduce on nematode-resistant soybean. H. glycines chorismate
      mutase-1 (Hg-CM-1) is a nematode enzyme with the potential to suppress host plant
      defense compounds; therefore, it has the potential to enhance the parasitic
      ability of nematodes expressing the gene. Hg-cm-1 is a member of a gene family
      where two alleles, Hg-cm-1A and Hg-cm-1B, have been identified. Analysis of the
      Hg-cm-1 gene copy number revealed that there are multiple copies of Hg-cm-1
      alleles in the H. glycines genome. H. glycines inbred lines were crossed to
      ultimately generate three F2 populations of second-stage juveniles (J2s)
      segregating for Hg-cm-1A and Hg-cm-1B. Segregation of Hg-cm-1A and 1B
      approximated a 1:2:1 ratio, which suggested that Hg-cm-1 is organized in a
      cluster of genes that segregate roughly as a single locus. The F2 H. glycines J2
      populations were used to infect nematode-resistant (Hartwig, PI88788, and
      PI90763) and susceptible (Lee 74) soybean plants. H. glycines grown on Hartwig,
      Lee 74, and PI90763 showed allelic frequencies similar to Hg-cm-1A/B, but
      nematodes grown on PI88788 contained predominately Hg-cm-1A allele as a result of
      a statistically significant drop of Hg-cm-1B in the population. This result
      suggests that specific Hg-cm-1 alleles, or a closely linked gene, may aid H.
      glycines in adapting to particular soybean hosts.

PMID- 15986931
TI  - When covering up is a good thing. Family physicians' role in educating the public
      about West Nile virus.

PMID- 15986930
TI  - Functional analysis of the cytochrome P450 monooxygenase gene bcbot1 of Botrytis
      cinerea indicates that botrydial is a strain-specific virulence factor.
AB  - The micrographic phytopathogen Botrytis cinerea causes gray mold diseases in a
      large number of dicotyledonous crop plants and ornamentals. Colonization of host
      tissue is accompanied by rapid killing of plant cells ahead of the growing
      hyphen, probably caused by secretion of nonspecific phytotoxins, e.g., the
      sesquiterpene botrydial. Although all pathogenic strains tested so far had been
      shown to secrete botrydial and although the toxin causes comparable necrotic
      lesions as infection by the fungus, the role of botrydial in the infection
      process has not been elucidated so far. Here, we describe the functional
      characterization of bcbot1, encoding a P450 monooxygenase and provide evidence
      that it is involved in the botrydial pathway, i.e., it represents the first
      botrydial biosynthetic gene identified. We show that bcbot1 is expressed in
      planta and that expression in vitro and in planta is controlled by an alpha
      subunit of a heterotrimeric GTP-binding protein, BCG1. Deletion of bcbot1 in
      three standard strains of B. cinerea shows that the effect on virulence (on
      several host plants) is strain-dependent; only deletion in one of the strains
      (T4) led to reduced virulence.

PMID- 15986932
TI  - Care for psychological problems. Collaborative approach in primary care.

PMID- 15986933
TI  - Help assessing seniors' driving.

PMID- 15986934
TI  - Pregnancy after stem cell transplantation.
AB  - QUESTION: A married woman under my care underwent successful bone marrow
      transplantation as part of treatment for a malignancy. She wishes to start a
      family. What are her chances? Are there risks? ANSWER: Success in becoming
      pregnant after stem cell transplantation depends on such factors as cumulative
      doses of chemotherapy and radiation and mother's age at time of transplant. There
      is increased risk of prematurity, low birth weight, and spontaneous abortion.
      Pregnancy should be managed as high risk.

PMID- 15986935
TI  - Writing postoperative orders.

PMID- 15986936
TI  - Being a camp doctor.

PMID- 15986937
TI  - Clinical pearls from the Cochrane Library.

PMID- 15986938
TI  - Vitamin E might increase risk of death.

PMID- 15986939
TI  - West Nile virus. Primer for family physicians.
AB  - OBJECTIVE: To provide primary care physicians with an understanding of West Nile
      virus in North America. This article focuses on epidemiology, clinical features,
      diagnosis, and prevention of infection. QUALITY OF EVIDENCE: MEDLINE and EMBASE
      searches revealed epidemiologic, surveillance, cohort, and outcome studies
      providing level II evidence. There were no randomized controlled trials of
      treatment. Recommended prevention and treatment strategies are based on level II
      and III evidence. MAIN MESSAGE: The mosquito-borne virus that first appeared on
      this continent in 1999 is now prevalent throughout North America. Most infections
      are asymptomatic. Fewer than 1% of those infected develop severe illness; 3% to
      15% of those with severe illness die. While methods for controlling the mosquito
      population are available, we lack evidence that they reduce infection in the
      general human population. Family physicians have an important role in advising
      their patients on ways to prevent infection and in identifying patients who might
      be infected with West Nile virus. CONCLUSION: The general population is at low
      risk of West Nile virus infection. Prevention of infection rests on controlling
      the mosquito population and educating people on how to protect themselves against
      mosquito bites.

PMID- 15986940
TI  - Pharmacologic treatment of migraine. Comparison of guidelines.
AB  - OBJECTIVE: To compare guidelines (not the primary studies) for pharmacologic
      treatment of migraine as to methods of guideline development; recommendations,
      particularly on triptans; and quality of supporting evidence (with emphasis on
      comparative studies of triptans versus ergot alkaloids and nonsteroidal anti
      inflammatory drugs [NSAIDs]). DATA SOURCES: We searched MEDLINE via PubMed for
      guidelines on migraine management published since 1990 in any language; in
      addition, we browsed the Internet for information. STUDY SELECTION: We found nine
      clinical guidelines on migraine; one guideline, not supported by references, was
      excluded. SYNTHESIS: Preference for triptans is not well founded and is largely
      based on comparisons with placebo. Too few studies compared new drugs with
      established ones (NSAIDs or dihydroergotamine). Guidelines that propose a
      hierarchy for selection of drugs are opinion-based rather than evidence-based.
      CONCLUSION: The current lack of evidence from comparative studies seriously
      limits development of evidence-based clinical practice guidelines for
      pharmacologic treatment of migraine.

PMID- 15986941
TI  - Case report: Recurrent aphthous stomatitis responds to vitamin B12 treatment.

PMID- 15986942
TI  - The Canadian Health Network. A new kind of referral.

PMID- 15986943
TI  - One year later. Starting a family medicine Student Interest Group.

PMID- 15986944
TI  - Dental amalgam is 50% mercury ... or is it?

PMID- 15986945
TI  - Three-year clinical evaluation of a compomer and a resin composite as Class V
      filling materials.
AB  - The purpose of this study was to evaluate the placement of two restorative
      materials, including a compomer (F2000, 3M ESPE) and a resin composite (Silux
      Plus, 3M ESPE), in non-carious cervical lesions using a self-etching bonding
      agent (F2000 self-etching primer/adhesive) and a fifth generation bonding agent
      (Single Bond, 3M ESPE) and to evaluate and compare these restorations for
      marginal discoloration, secondary caries, anatomical form, retention, surface
      texture and marginal adaptation at baseline and annually for three years. F2000
      and Silux Plus were used to restore the teeth with moderate-sized non-carious
      cervical lesions. F2000 was placed using two different bonding agents: F2000 self
      etching primer/adhesive (F2000SE group) and Single Bond (F2000SB group); Silux
      Plus was placed as a control using Single Bond (SiluxSB group). Thirty
      restorations of each material/dentin adhesive combination were placed. All
      restorations were evaluated at baseline and annually for three years using a
      modified USPHS scale. At the end of the three-year recall, Silux Plus had
      significantly better surface texture than F2000 (p < 0.0001). In addition,
      marginal adaptation significantly worsened over time starting at one year, as
      compared with baseline, for all groups (p < 0.0001). When anatomic form was
      compared between F2000 and Silux Plus, the p-value was 0.085, demonstrating that
      F2000 was slightly better than Silux Plus. Likewise, when comparing marginal
      adaptation between the F2000SE and SiluxSB groups, the p-value was 0.064,
      demonstrating that F2000 with the self-etching primer had better margins than
      Silux Plus with Single Bond. No other differences were found among the groups.

PMID- 15986946
TI  - Two-year clinical performance of occlusal and cervical giomer restorations.
AB  - This study evaluated the two-year clinical performance of two types of giomers
      (Beautifil, a surface reaction giomer and Reactmer, a full-reaction giomer), in
      occlusal (Class I) and cervical (Class V) cavities using the USPHS criteria.
      Forty-two cervical erosion and carious lesions were restored using Beautifil and
      Reactmer following manufacturer's instructions. Twenty occlusal cavities were
      restored with Beautifil. Fifteen patients (mean age 35, ranging in age from 20 to
      50 years) participated in the study. The success rate for cervical Beautifil
      restorations after two years was 80%, while the success rate for cervical
      Reactmer restorations was 71%. Occlusal Beautifil restorations had a 100% success
      rate.

PMID- 15986947
TI  - Two-year clinical evaluation of a posterior resin composite using a fourth- and
      fifth-generation bonding agent.
AB  - This study evaluated the clinical performance of a posterior resin composite used
      with a fourth- and fifth-generation bonding agent. Sixty-two Class I and II
      restorations were placed with half the restorations restored with Gluma Solid
      Bond (a fourth-generation bonding system, or total etch two-step system) and the
      other half restored with Gluma Comfort Bond and Desensitizer (a fifth-generation
      bonding system, or total etch one-step system). Solitaire 2 was used as the
      restorative material for all restorations. The bonding systems and resin
      composite were used according to the manufacturer's instructions and all
      procedures were performed with rubber dam isolation. All restorations were
      evaluated at baseline, six months and one and two years. A modified USPHS scale
      was used to evaluate the restorations for marginal discoloration, recurrent
      caries, anatomic form, marginal adaptation and proximal contact. Statistical
      analysis revealed that at two years no significant differences were found between
      the two bonding agents. Overall, Solitaire 2 performed well clinically whether
      Gluma Solid Bond or Gluma Comfort Bond and Desensitizer was used. It was thus
      concluded that Solitaire 2 functions successfully when used as a posterior
      restorative material for at least two years.

PMID- 15986949
TI  - Hybrid layer thickness and morphology: the influence of cavity preparation with
      Er:YAG laser.
AB  - Dentinal surfaces prepared with Er:YAG laser have significantly different
      characteristics from those prepared with conventional instruments. Different
      hybrid layer morphologies and thicknesses occur, which may result in differences
      in the quality of restorations placed on dentinal surfaces prepared with a
      diamond bur when compared with using an Er:YAG Laser. This study compared the
      hybrid layer thickness and morphology formed utilizing Scotchbond Multipurpose
      Plus (SBMP) on dentin prepared with a diamond bur in a high speed handpiece and
      dentin prepared with an Er:YAG laser. Flat dentin surfaces obtained from five
      human teeth were treated with the two methods and then with the dentin adhesive
      system according to the manufacturer's instructions. After a layer of composite
      was applied, the specimens were sectioned, flattened, polished and prepared for
      SEM observation. Ten different measurements of hybrid layer thickness were
      obtained along the bonded surface in each specimen. Results showed that SBMP
      produced a 3.43 +/- 0.75 microm hybrid layer in dentin prepared with a diamond
      bur. This hybrid layer was regular and constantly found. In the laser group, the
      dentin adhesive system produced a 1.54 +/- 0.35 microm hybrid layer that was very
      irregular and not found constantly. Statistical analysis of variance (p < 0.05)
      showed that there was a statistically significant difference between the groups.
      These data indicate that the Er:YAG laser, with parameters used in the
      experiment, is not a preparation method that allows for a thick hybrid layer
      formation, which is in opposition to using a diamond bur in a high speed turbine.

PMID- 15986948
TI  - Effects of five thermal stressing regimens on the flexural and bond strengths of
      a hybrid resin composite.
AB  - Thermocycling is commonly employed in laboratory studies to simulate the in vivo
      aging of restorative materials. However, there is little consistency in the
      regimens used, and some researchers have questioned the clinical relevance and,
      hence, the necessity of including thermal stressing in in vitro protocols. This
      study examined the effects of five thermal stressing regimens on the flexural and
      dentin bond strengths of a hybrid resin composite. METHODS: For flexural strength
      tests, 95 rectangular specimens (15 mm x 2 mm x 2 mm) were fabricated using a
      stainless steel split mold, then light cured for 60 seconds. For bond strength
      tests, 75 caries-free molars were flattened occlusally to expose dentin, then
      polished through 600 grit SiC paper; dentin surfaces were etched, rinsed and
      blotted dry. A dentin adhesive was applied and light cured for 30 seconds; resin
      composite was condensed through a stainless steel split mold (4.3 mm diameter x
      3.5 mm high), then light cured for 60 seconds. All specimens were stored in
      deionized water for 24 hours, then stressed for 100 hours according to one of
      five regimens: 1) cycled between 5 degrees C and 55 degrees C (9000 cycles; 20
      second dwell time); 2) held at 5 degrees C constant; 3) held at 22 degrees C
      constant; 4) held at 55 degrees C constant; 5) held at 5 degrees C for 50 hours,
      then at 55 degrees C for 50 hours. Flexural strengths were measured using an
      Instron 5500R and three-point bending apparatus at a crosshead speed of 0.5
      mm/minute. Shear bond strengths were measured using an MTS Bionix 200 at a
      crosshead speed of 0.5 mm/minute. RESULTS: ANOVA revealed no significant
      differences in either flexural strength or shear bond strength among the five
      thermal regimens.

PMID- 15986950
TI  - The microtensile bond strength of Fuji IX glass ionomer cement to antibacterial
      conditioned dentin.
AB  - INTRODUCTION: Adding antibacterial agents to a dentin conditioner used for a
      glass ionomer cement (GIC) has been shown to be antibacterial; however, it is not
      known whether this antimicrobial conditioning agent affects the bond strength to
      dentin in situ. This study applied GIC to antibacterial conditioned dentin
      without rinsing and determined whether there is an affect on the material's bond
      strength. MATERIALS AND METHODS: Chlorhexidine acetate (CX), benzalkonium
      chloride (BC) and cetrimide (CT) were added to Dentin Conditioner (DC) (GC Corp,
      Japan) at 1% and 5% concentrations. Molars were sectioned coronally to expose
      dentin, onto which 50 microl of the test conditioners was applied for 20 seconds
      with a gentle scrubbing action and the residual liquid was blotted dry, as would
      occur under "field" conditions when performing atraumatic restorative therapy. To
      serve as the control, the DC was left in situ and compared to the DC that was
      washed off. Proportioned Fuji IX GIC (GC Corp, Japan) was built-up on the
      prepared dentin surface and varnish was applied and stored for 24 hours. An
      annular saw was used to create sticks of GIC bonded to dentin, with a bonding
      area 1 mm2. After 24 hours, the specimens were tested to failure in a Universal
      testing machine at a crosshead speed of 1 mm/minute. RESULTS: Five percent CX-DC
      was not tested, as it formed a precipitate. Results in MPa: DC-not washed, 9.3 +/
      2.4; DC-washed, 9.3 +/- 2.5; 1% BC-DC, 8.8 +/- 2.5; 1% CX-DC, 8.7 +/- 2.7; 1% CT
      DC, 8.2 +/- 1.7; 5% CT-DC, 8.1 +/- 2.7; 5% BC-DC, 5.4 +/- 1.0. One-way ANOVA
      showed that there was a significant difference between the test groups (p <
      0.05), and Tukey's studentized range test showed that only 5% BC-dentin
      conditioner left in situ was significantly different from the other groups.
      CONCLUSION: Under the conditions tested, only the 5% BC-DC left in situ affected
      the bond strength of Fuji IX to dentin.

PMID- 15986951
TI  - Effect of peroxide-based bleaching agents on enamel ultimate tensile strength.
AB  - This study evaluated the effects of peroxide bleaching regimens on the ultimate
      tensile strength (UTS) of human enamel. A resin composite block was built-up on
      the bonded occlusal surface of 14 extracted, sound, erupted third molars to
      enable posterior preparation for the microtensile test. The bonded teeth were
      serially sectioned in a buccal-lingual direction into approximately 0.7-mm thick
      slices. Each slice was trimmed with a fine diamond bur to reduce the area of the
      buccal, internal slope of the cusps to a dumb-bell shape with a cross-sectional
      area of less than 1 mm2. The samples were randomly divided into seven groups (n =
      10): unbleached control group and bleached groups treated with six bleaching
      regimens. The specimens were tested in tension at 0.5 mm/minute and the data were
      analyzed by ANOVA and Tukey test. Specimens from the control group presented 51.3
      +/- 8.6 MPa, while the UTS of bleached enamel ranged from 22.0 +/- 5.6 to 36.3 +/
      9.1 MPa. All bleaching procedures significantly reduced enamel UTS (p < 0.05).
      Differences were also observed among treatments. The results suggested that
      bleaching regimens can significantly reduce enamel UTS.

PMID- 15986952
TI  - Liner and light exposure: effect on in-vitro Class V microleakage.
AB  - This in vitro study evaluated the influence of different glass ionomer liners and
      curing methods on microleakage of resin composite restorations. Class V root
      preparations were made in 120 bovine incisors randomly divided into 12 groups
      according to liner and curing method. The resin composite system (Single Bond +
      Z100) was inserted and polymerized in one increment in all groups. Cavity
      preparations were either not lined (control), lined with a resin modified glass
      ionomer cement (Vitrebond) or a conventional glass-ionomer cement (Ketac Bond).
      The restorations were light-cured using one of four curing methods. The teeth
      were thermocycled and immersed in 0.5% basic fuchsin, sectioned, and dye
      penetration was measured (Image Tool). No significant difference in leakage among
      conventional, ramp or pulse-delay methods was seen. High intensity light groups
      showed significantly greater penetration compared to other curing methods. No
      significant difference existed in marginal leakage between liners, but
      microleakage was significantly higher in groups restored using no liner. No
      relationship between lining technique and light curing method was observed. The
      use of glass ionomer liners reduced microleakage, while high intensity light
      curing produced the greatest dye penetration.

PMID- 15986953
TI  - Coronal microleakage of temporary restorations in previously restored teeth with
      amalgam and composite.
AB  - AIM: This study evaluated microleakage at the interface between various temporary
      restorative materials and existing amalgam or composite restorations, and dental
      tissues in previously restored teeth after partial removal of the restoration.
      MATERIALS AND METHODS: The distal half of amal gam (Ag) and composite
      restorations (Co) in 45 teeth were removed, then filled with temporary
      restorative materials (IRM, Coltosol and CLIP). After thermal cycling,
      microleakage was measured microscopically as the penetration of basic fuchsine
      according to a four-unit-scale: The data were evaluated with Friedman and Kruskal
      Wallis tests using Bonferroni correction (p < 0.05). RESULTS: In almost all
      groups except the Co-IRM and Ag-CLIP interface, lower microleakage values were
      observed in temporary restoration-permanent restoration interfaces compared to
      temporary restoration-tooth interfaces. For the Ag and Co groups except for the
      Ag-IRM-b interfaces, the highest microleakage values were observed with IRM for b
      and c interfaces followed by Coltosol and CLIP. Interestingly, although CLIP was
      a temporary restoration, CLIP-tooth interface (Ag-CLIP-c) values were lower than
      amalgam-tooth interface (Ag-CLIP-a) values. CONCLUSIONS: CLIP provided a better
      seal against microleakage at amalgam and especially composite interfaces. This
      material also provided a better seal against microleakage at the tooth tissue
      interface. The use of a resin based temporary restorative material over partially
      removed resin composite restorations could be beneficial in achieving better
      resistance to marginal leakage. Within the limitations of this study, maintaining
      partially removed permanent restorations does not seem to cause a problem with
      achieving marginal seal.

PMID- 15986954
TI  - Factors affecting microleakage of a packable resin composite: an in vitro study.
AB  - This study was designed to determine the effects of three factors on the
      microleakage of a packable resin composite: different adhesive systems (single
      step self-etching adhesive or total-etch and one-bottle adhesive), the use of a
      flowable resin composite (as a liner) and the different techniques of cavity
      preparation. Sixty extracted non-carious human first and second molars were
      selected and randomly divided into six groups. Cervical cavities were prepared
      using the conventional technique on the distal sides and the air-abrasive
      technique was used on the mesial sides of the teeth. The experimental groups were
      restored with PQ1 + SureFil or Prompt L-Pop + SureFil with or without PermaFlo.
      In the control groups, only SureFil was used on 10 teeth and PermaFlo + SureFil
      was applied on the remaining 10 teeth. The restored teeth were stored in 100%
      humidity at 37 degrees C for 24 hours and thermocycled between 5 degrees C and 55
      degrees C for 100 cycles. Each tooth was immersed in India ink for 48 hours, then
      sectioned. Dye penetration at the occlusal and gingival margins was scored by two
      independent operators. The data were statistically analyzed to assess the
      differences between the test and control groups. No significant differences among
      the adhesives in terms of the occlusal margins of the cavities were observed.
      However, PQ1 led to less microleakage compared to Prompt L-Pop at the gingival
      margins (p < 0.0062). When flowable resin composite was used with Prompt L-Pop,
      microleakage was reduced (p < 0.0125). However, no significant difference was
      observed between the two cavity preparation techniques (p > 0.0125).

PMID- 15986955
TI  - Measurement of linear polymerization contraction using digital laser
      interferometry.
AB  - Polymerization shrinkage is an unavoidable consequence of resin composite
      photopolymerization and is one of the most important factors in determining the
      clinical quality and durability of composite filling. Many different methods of
      measuring polymerization shrinkage are described in the literature. Digital laser
      interferometry is a method that enables direct observation of polymerization
      shrinkage in real time. This study used the digital holographic interferometry
      method to measure the linear polymerization contraction of composite materials:
      Tetric Ceram (Vivadent), Spectrum TPH (Dentsply) and Valux Plus (3M Dental
      Products) polymerized with three different curing modes of the Elipar Trilight
      (ESPE) halogen curing unit. The highest polymerization contraction was recorded
      by "standard mode" (ETS) (1.24 +/- 2.66% lin), and the lowest by "medium mode"
      (ETM) (0.40 +/- 0.41% lin) during 40 second illumination. The "exponentional
      mode" (ETE) showed the highest expansion during the first 10 seconds of
      illumination. Curing units with initial low intensity enable better inner
      adaptation of composite material, preventing the detachment of material from
      dentin during polymerization and avoiding the negative consequences of
      polymerization shrinkage.

PMID- 15986956
TI  - Influence of NaOCl treatment of etched and dried dentin surface on bond strength
      and resin infiltration.
AB  - This study evaluated the effect of NaOCl treatment of etched air-dried dentin on
      the bond strength and state of monomer penetration. Ten percent NaOCl was applied
      after rinsing the etchant and air drying the dentin surface. Wet bonded,
      untreated teeth were used as a control. The resin composite was bonded and stored
      in 37 degrees C water for 24 hours, then shear tested. One-way ANOVA, followed by
      the Duncan test, was done. For Raman microscopy, bonded specimens were cut
      parallel to the dentinal tubules and polished. Raman spectra were successively
      recorded along lines perpendicular to the dentin-adhesive interface. The
      decreased bond strengths found with air-dried dentin increased with NaOCl
      treatment, but the highest bond strength was obtained with wet bonding. From
      Raman spectroscopy, the widths of demineralized dentin decreased with prolonged
      NaOCl treatment time. The patterns of gradual transition of components differed
      among the groups.

PMID- 15986957
TI  - Influence of metal conditioner contamination of the dentin surface on bond
      strengths of dentin adhesive systems using self-etching primers.
AB  - Carious lesions around crown margins sometimes lead to failure of fixed
      prosthodontics. This study examined the influence of metal conditioner
      application on a dentin surface prior to bonding procedures, using two-step self
      etching primer systems. Commercially available metal conditioners and self
      etching primer dentin bonding systems were used. Bovine mandibular incisors were
      mounted in self-curing resin, and the facial dentin surfaces were ground wet on
      600-grit SiC paper. The metal primers were applied on the dentin surface followed
      by bonding procedures with four different types of self-etching primer systems.
      The resin composites were condensed into a mold on the dentin surface and light
      activated. Ten specimens per test group were stored in 37 degrees C water for 24
      hours; they were then shear tested at a crosshead speed of 1.0 mm/minute. Two-way
      ANOVA and Tukey's HSD tests were done. When the metal conditioners were applied
      on dentin surfaces before bonding procedures, there was a tendency for decreased
      dentin bond strengths compared to those obtained with the controls. This tendency
      differed among the combinations of metal conditioners and self-etching primer
      systems used. Appropriate surface treatments are required to get optimum bond
      strengths with the use of technique sensitive bonding systems combined with metal
      conditioners.

PMID- 15986958
TI  - In vitro evaluation of the cariostatic action of esthetic restorative materials
      in bovine teeth under severe cariogenic challenge.
AB  - Considering that caries around restorations is a serious problem in dentistry,
      and some restorative materials with fluoride may be important in inhibiting these
      lesions, this research is aimed at performing an in vitro evaluation of the
      cariostatic action of some esthetic restorative materials. Standardized cavities
      were prepared in the center of either intact blocks of bovine enamel or with
      bovine teeth containing early artificial carious lesions. The specimens were
      restored with a high viscosity glass ionomer cement (Molar Ketac), a resin
      modified glass ionomer cement (Vitremer), a polyacid-modified resin composite
      (Dyract AP) and a conventional resin composite (Z-250). In addition to the
      restored specimens, four corresponding control groups were evaluated. All groups,
      except for two control groups, were subjected to a
      demineralization/remineralization cycling model for 14 days, simulating a
      situation of severe cariogenic challenge. The blocks were then longitudinally
      sectioned through the restorations. Mineral loss was evaluated in these specimens
      using the Knoop microhardness profiles in longitudinal sections at three
      different distances of the cavities and at eight distinct depths in relation to
      the external enamel surface. Statistical analysis of the results showed
      significant differences (p < 0.05) among the groups, although none of the study
      materials completely inhibited creation of the lesions. Vitremer demonstrated the
      best cariostatic action in intact bovine enamel. Ketac Molar, in intact or
      demineralized enamel, and Vitremer, in demineralized enamel, presented
      intermediate cariostatic potential. Z-250 and Dyract AP did not demonstrate any
      cariostatic effect. The data suggests that glass ionomer cements demonstrated
      better cariostatic action compared to the other restorative materials.

PMID- 15986959
TI  - Effect of solvent type on microtensile bond strength of a total-etch one-bottle
      adhesive system to moist or dry dentin.
AB  - This study evaluated the effect of organic solvent (acetone or ethanol) on the
      microtensile bond strengths (MTBS) of an adhesive system applied to dry and moist
      dentin. Sixteen extracted human third molars were ground to expose a flat
      occlusal dentin surface and acid etched for 20 seconds (20% phosphoric acid gel,
      Gluma Etch 20 Gel, Heraeus/Kulzer). After rinsing the acid etchant, an ethanol
      based one-bottle adhesive system was applied to the mesial half of the occlusal
      dentin surface. An acetone-based, one-bottle adhesive system was applied to the
      distal half of the ground dentin surface. The teeth were randomly assigned to
      groups. In Group 1, the etched dentin was thoroughly air dried and an ethanol
      based one-bottle adhesive system was applied (Gluma Comfort Bond, Heraeus/Kulzer)
      (GCB). In Group 2, the etched dentin was thoroughly air dried and an acetone
      based one-bottle adhesive system was applied (Gluma One Bond,
      Heraeus/Kulzer)(GOB). In Group 3, excess moisture was removed after acid etching,
      leaving a moist dentin surface and a one-bottle ethanol-based adhesive was
      applied (Gluma Comfort Bond). In Group 4, excess moisture was removed after acid
      etching, leaving a moist dentin surface and an acetone-based adhesive was applied
      (Gluma One Bond). A hybrid resin composite (Venus, Heraeus/Kulzer) was applied to
      the bonded surface in four 1-mm increments and light cured according to
      manufacturer's directions. The specimens were then sectioned with a slow-speed
      diamond saw in two perpendicular directions to obtain sticks with a cross-section
      of 0.5 +/- 0.05 mm2. The microtensile bond strength (MTBS) test was performed
      with a Bencor device in an Instron machine at a crosshead speed of 0.5 mm/minute.
      The data were subjected to a two-way ANOVA and Scheffe Post hoc test (p < 0.05).
      The experimental MTBS measured for dry dentin were Group 1 = 37.0 +/- 10.6 and
      Group 2 = 34.7 +/- 9.0 in MPa (mean +/- SD); and on moist dentin, Group 3 = 50.7
      +/- 11.0 and Group 4 = 38.5 +/- 10.5 in MPa (mean +/- SD). The ethanol based
      adhesives resulted in higher MTBS than acetone-based adhesive (p < 0.008) and
      bonding to moist dentin resulted in higher MTBS (p < 0.001). GCB applied on moist
      dentin resulted in statistically higher bond strengths than the other groups. The
      highest MTBS were achieved with the use of an ethanol-based adhesive to moist
      dentin.

PMID- 15986960
TI  - The shear bond strength between luting cements and zirconia ceramics after two
      pre-treatments.
AB  - This study evaluated the shear-bond strength of 11 luting cements from different
      material classes to manufactured pre-treated zirconia ceramics (Lava: 97% ZrO2,
      stabilized with 3% Y2O3). In addition, the influence of the curing method on
      shear-bond strength was investigated. The cements examined were one zinc
      phosphate cement (Fleck's zinc cement), two standard glass-ionomer cements (Fuji
      I, Ketac-Cem), three resin-modified glass-ionomer cements (Fuji Plus, Fuji Cem,
      RelyX Luting), four standard resin cements (RelyX ARC, Panavia F, Variolink II,
      Compolute) and one self-adhesive universal resin cement (RelyX Unicem). The
      ceramic surface was sand-blasted with 100-microm alumina or tribochemically
      coated with silica. After bonding procedure, one group was tested after 30
      minutes (Time I), the other group was stored in distilled water at 37 degrees C
      for 14 days and subsequently thermocycled 1000 times (Time II). Statistical
      analysis was performed by multifactorial ANOVA models with interactions. For
      multiple pairwise comparisons, the Tukey method was used. After sandblasting, the
      highest shear-bond strength was obtained for the self-adhesive universal resin
      cement at 9.7 MPa (Time I) and 12.7 MPa (Time II), respectively. When using the
      Rocatec system, the highest values were found for one of the resin cements at
      15.0 MPa (Time I) and for the self-adhesive universal resin cement at 19.9 MPa
      (Time II).

PMID- 15986961
TI  - Mechanical properties of light-cured composites polymerized with several
      additional post-curing methods.
AB  - This study determined the microhardness and diametral tensile strength of two
      hybrid resin composites submitted to conventional light curing, which were post
      cured with different methods, and compared these data with the same data
      collected from one indirect resin composite. Two hybrid composites (TPH Spectrum
      and Filtek P60) and an indirect one (Solidex) were used. Conventional composites
      were polymerized with 1) conventional light curing for 40 seconds. Additional
      curing methods were applied with 2) laboratory multi-focal light curing for seven
      minutes, 3) microwave curing for five minutes at 500W, 4) oven curing for 15
      minutes at 100 degrees C, 5) autoclave curing for 15 minutes at 100 degrees C and
      (6) were polymerized only with a laboratory light curing unit in three increments
      for three minutes and post-polymerized for seven minutes. The Solidex group was
      done following the manufacturers' instructions only. Diametral tensile strength
      and Knoop hardness tests were applied for all groups of five samples. Data were
      compared using ANOVA, Tukey and Student t-tests (p < 0.05). Post-curing methods
      increased the Knoop hardness and diametral tensile strength of conventional
      composites. In general, Filtek P60 showed higher hardness and diametral tensile
      strength values than TPH Spectrum resin. The Indirect resin composite showed
      poorer mechanical properties than conventional composites.

PMID- 15986962
TI  - Restoring erosion associated with gastroesophageal reflux using direct resins:
      case report.
AB  - Gastroesophageal reflux disease (GERD) is a condition where stomach acids are
      chronically regurgitated into the esophagus and oral cavity, resulting in
      pathology, such as esophagitis, varices or ulcers. Continual exposure of the
      teeth to these acids can also cause severe dental erosion. This condition
      frequently is asymptomatic, and the only evident sign may be the irreversible
      erosion of tooth structure. The dentist often is the first health care
      professional to identify the affected dentition. Knowledge of this cause and
      effect relationship between GERD and dental erosion will better prepare the
      practitioner to refer patients for appropriate diagnosis and treatment of the
      underlying medical condition and provide treatment for the affected teeth. This
      article presents a case report where dental erosion was present due to GERD.
      After management of the disease with medication, dental treatment of the eroded
      dentition is described, including diagnosis, treatment planning and restorative
      reconstruction.

PMID- 15986963
TI  - Immediate esthetic management of a catastrophically fractured anterior.
AB  - A quick, failsafe method for the esthetic replacement of a catastrophically
      fractured anterior tooth was presented. This method required minimal
      armamentarium and no anesthesia. In addition, it employed a technique that is not
      technique sensitive. The patient and the dental team both benefit by resolving
      the esthetic crisis using simple methods and excellent time resource management.

PMID- 15986964
TI  - Bariatric surgery: malpractice risks and risk management guidelines.
AB  - Providing appropriate medical care to bariatric surgery patients is the primary
      goal of every surgeon. However, with the expected growth of bariatric surgery in
      the future, the number of claims in this area are certain to grow. Therefore, it
      is important for surgeons who are engaged in the practice of bariatric surgery or
      who are contemplating entering the practice of bariatric surgery to consider risk
      management guidelines and principles very carefully. It is important to follow
      the available guidelines and criteria like those established by the American
      Society of Bariatric Surgery to help reduce the risk of liability. Despite
      appropriate care and treatment, unfortunately, these patients will continue to
      suffer complications, some of which are life-threatening. The importance of
      establishing and maintaining a solid physician-patient relationship by using
      appropriate interpersonal skills cannot be overemphasized. Indeed, a good
      relationship with the patient and family remains the most effective way of
      reducing the risk of being sued when there is an unfortunate complication, as
      well as increasing the chances of a successful defense in the event of suit.

PMID- 15986965
TI  - Nonoperative management of blunt splenic injury in infectious mononucleosis.

PMID- 15986966
TI  - Assessment of nonoperative management of blunt spleen and liver trauma.
AB  - An 8-year analysis of nonoperative management (NOM) of spleen and liver trauma
      was done in a level 1 trauma center. Spleen and liver trauma was diagnosed in 279
      patients: 93 children (<18), 137 younger adults (18-54), and 49 older adults (>
      or = 55). Nineteen patients who failed resuscitations died within 0-60 minutes of
      arrival and were excluded from treatment analysis. Operative management (OM) was
      done in 39 (15%) and NOM in 221 (85%) patients with failure (NOMF) in 11 (5%).
      NOM and NOMF was 82 per cent and 5.6 per cent in spleen, 74 per cent and 14.3 per
      cent in combined spleen/liver, and 96 per cent and 1.5 per cent in liver trauma
      (P value <0.001). NOM was done in 99 per cent of children, 81 per cent of younger
      adults, and 68 per cent of older adults with 0 per cent, 8 per cent, and 10 per
      cent NOMF. Higher grades of splenic trauma and CT fluid had higher OM rate. NOM
      success rates were 93.8 per cent in grade 3 and 90.3 per cent in higher grades of
      spleen trauma. There was no NOMF in higher grades of liver trauma. CT fluid grade
      had no impact on NOMF. Female patients had higher mean injury severity score,
      age, and mortality compared to cohorts. NOM should be attempted in
      hemodynamically stable patients. Age over 55, higher grades of injury, and large
      hemoperitoneum were not predictors of failure of NOM.

PMID- 15986967
TI  - Deep venous thrombosis and pulmonary embolism in trauma patients: an
      overstatement of the problem?
AB  - Deep venous thrombosis (DVT) and pulmonary embolism (PE) affect high-risk trauma
      patients (HRTP). Accurate incidence and clinical importance of DVT and PE in HRPT
      may be overstated. We performed a ten-year retrospective analysis of HRTP of the
      Pennsylvania Trauma Outcome Study. High-risk factors (HRF) included pelvic
      fracture (PFx), lower extremity fracture (LEFx), severe head injury (CHI) (AIS -
      head > or =3), and spinal cord injury. HRF alone or in combination, age, Injury
      Severity Score (ISS), and Glasgow Coma Score (GCS) were examined for association
      with DVT/PE. A total of 73,419 HRTP were included: 1377 (1.9%) had DVT, 365
      (0.5%) had PE. The incidence of DVT in level I trauma centers was 2.2 per cent
      and was 1.5 per cent in level II centers. The lowest incidence of DVT was 1.3 per
      cent for isolated LEFx; highest was 5.4% for combined PFx, LEFx, and CHI.
      Variables associated with DVT included age, ISS, and GCS (all P < 0.001). In
      logistic regression analysis, only ISS was consistently predictive for DVT and
      PE. Though increased during the past decade, the overall incidence of DVT in HRTP
      remains below 3 per cent. Only the combination of multiple injuries or an ISS >30
      result in DVT incidence of > or =5 per cent. We believe that current guidelines
      for screening for DVT may need to be reevaluated.

PMID- 15986968
TI  - CT-angiography for the detection of a lower gastrointestinal bleeding source.
AB  - The evaluation of lower gastrointestinal bleeding (LGIB) often involves the
      collaborative efforts of the gastroenterologist, radiologist, and surgeon.
      Efforts to localize the acute LGIB have traditionally involved colonoscopy,
      technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a
      combination of these modalities. The sensitivity of each method of diagnosis is
      limited, with the most common cause of a negative study the spontaneous cessation
      of hemorrhage. Other technical factors include vasospasm, lack of adequate
      contrast volume or exposure time, a venous bleeding source, and a large surface
      bleeding area. We report the use of multidetector computed tomography (MDCT), or
      CT-angiography (CT-A), in the initial evaluation of LGIB, and speculate on the
      incorporation of this technique into a diagnostic algorithm to treat LGIB. MDCT
      may offer a very sensitive means to evaluate the source of acute LGIB, while
      avoiding some of the morbidity and intense resource use of contrast angiography,
      and may provide unique morphologic information regarding the type of pathology.
      Screening with the more rapid and available MDCT, followed by either directed
      therapeutic angiography or surgical management, may represent a reasonable
      algorithm for the early evaluation and management of acute LGIB in which an
      active bleeding source is strongly suspected.

PMID- 15986969
TI  - Single-stage reconstruction of perforated choledochal cyst: case report and
      review of the literature.
AB  - Choledochal cysts represent a rare disease in the Western world. We reviewed our
      recent experience with a case of perforated choledochal cyst, define the
      currently accepted treatment options, and review the literature of this unusual
      disease. An 11-month-old girl presented with abdominal pain and distention as
      well as non-bilious vomiting. Subsequent workup included endoscopic retrograde
      cholangiopancreatography revealing a perforated type I choledochal cyst. She
      underwent single-stage excision and reconstruction with a Roux-en-Y
      hepaticojejunostomy. Perforated choledochal cyst is a rare event, and prompt
      surgical intervention is warranted. Single-stage cystectomy and Roux-en-Y
      reconstruction is possible in select patients. A thorough understanding of the
      pathophysiology, management, and follow-up is required.

PMID- 15986970
TI  - Multiple laparotomies are a predictor of fascial dehiscence in the setting of
      severe trauma.
AB  - The purpose of this study was to determine the incidence of wound dehiscence
      after repeat trauma laparotomy. We performed a retrospective analysis of adult
      trauma patients who underwent laparotomy at an urban level 1 trauma center during
      the past 5 years. Patients were divided into single (SL) and multiple laparotomy
      (ML) groups. Demographic, clinical, and outcome data were collected. Data were
      analyzed using chi2, t testing, and ANOVA. Overall dehiscence rate was 0.7 per
      cent. Multiple laparotomy patients had damage control, staged management of their
      injuries, or abdominal compartment syndrome as the reason for reexploration. SL
      and ML patients had similar age and sex. ML patients had a higher rate of intra
      abdominal abscess than SL patients (13.7% vs 1.2% P < 0.0001), but intra
      abdominal abscess did not predict wound dehiscence in the ML group (P = 0.24).
      This was true in spite of the fact that ML patients had a significantly higher
      Injury Severity Score (ISS) than SL patients (21.68 vs 14.35, P < 0.0001).
      Interestingly, wound infection did not predict dehiscence. Patients undergoing
      repeat laparotomy after trauma are at increased risk for wound dehiscence. This
      risk appears to be associated with intraabdominal abscess and ISS, but not wound
      infection. Surgeons should leave the skin open in the setting of repeat trauma
      laparotomy, which will allow serial assessment of the integrity of the fascial
      closure.

PMID- 15986971
TI  - National analysis of adverse patient safety for events in bariatric surgery.
AB  - Identifying risk factors for adverse events after bariatric surgery (BaS) can
      help define high-risk groups to improve patient safety. We calculated cumulative
      incidence of adverse events and identified risk factors for these events using
      validated surgical patient safety indicators (PSIs) developed by the Agency for
      Healthcare Research and Quality. BaS patients > or =18 years old were identified
      using the 2002 Nationwide Inpatient Sample. Cumulative incidence at discharge was
      calculated for accidental puncture or laceration (APL), pulmonary embolus or deep
      venous thrombosis (PE/DVT), and postoperative respiratory failure (RF). Factors
      predictive of these PSIs were identified. From 7,853,982 discharges, a national
      cohort of 69,490 BaS patients was identified. During BaS hospitalization, the
      cumulative incidences per 1000 discharges of APL, PE/DVT, and RF were 12.6, 3.4,
      and 7.3, respectively. Risk factors for APL included male gender (odds ratio [OR]
      1.6, 95% confidence interval 1.1-2.3, P < 0.05) and age of 40-49 years (OR 1.6
      [1.1-2.3], P < 0.05) compared to ages 18-39 years. Patients aged 50-59 years (OR
      3.5 [1.6-7.7], P < 0.05) had a higher chance of PE/DVT compared to those 18-39
      years. Male gender (OR 1.8 [1.1-2.9], P < 0.05), ages 40-49 (OR 2.1 [1.1-4.2], P
      < 0.05) and 50-59 (OR 3.8 [2.1-6.9], P < 0.05), a history of chronic lung disease
      (OR 1.7 [1.1-2.7], P < 0.05), and Medicare coverage compared to private insurance
      (OR 2.2 [1.2-3.8], P < 0.05) were predictive of RF. This study established
      national measures for BaS adverse events. Further, risk factors associated with
      adverse events varied by gender, age, insurance status, and comorbidity.
      Evaluation of these higher risk BaS groups is needed to improve patient safety.

PMID- 15986972
TI  - A Jehovah's Witness with complex abdominal trauma and coagulopathy: use of factor
      VII and a review of the literature.
AB  - Management of acute bleeding in patients who are Jehovah's Witnesses remains a
      challenge. Clearly, the most important concept is meticulous and early hemostasis
      to minimize ongoing blood loss. This is generally followed by supportive
      measures. Dilutional coagulopathy can present a real challenge, as therapeutic
      options are quite limited in this group of patients. We present a patient who
      arrived in hemorrhagic shock, and despite early surgical therapy, his significant
      blood loss caused dilutional coagulopathy that we treated with activated factor
      VIIa. While use of factor VIIa after injury is gaining popularity, data on its
      use in patients who are Jehovah's Witnesses is quite limited. In this case, we
      believe the product was life-saving. Most importantly, there were no religious
      objections to its use. In appropriate patients, when surgical bleeding is
      controlled and there is still evidence of dilutional coagulopathy, factor VIIa
      may have a real role in patients, particularly those who are Jehovah's Witnesses.

PMID- 15986973
TI  - Initial chest tube management after pulmonary resection.
AB  - Tube thoracostomy management with suction or water seal after anatomical
      pulmonary resection remains somewhat controversial. Initial chest tube management
      may influence the duration of pleural fluid drainage, duration of tube
      thoracostomy, and/or hospital length of stay following pulmonary resection. We
      hypothesized that initial chest tube management with water seal decreases time
      for chest tube removal and decreases time of hospital stay. A retrospective chart
      review was performed on 109 consecutive patients who underwent lobectomy or
      segmentectomy in Western Pennsylvania Hospital between December 1999 and December
      2003. Comparison was made between chest tube management of water seal or suction
      in patients with and without air leak. Of the 109 patients, 78 (72%) had no air
      leak at the completion of surgery, and 31 (28%) had air leak. In the group
      without air leak (n = 78), water seal was used in 32 (41%) patients and suction
      in 46 (59%). In patients placed to water seal initially after surgery (n = 32),
      removal of chest tubes was on postoperative day (POD) 3.19 +/- 0.24 and hospital
      discharge was on POD 5.13 +/- 0.61. In patients placed to suction initially (n =
      46), chest tubes were removed on POD 4.52 +/- 0.40. Hospital discharge was on POD
      6.74 +/- 0.5. Both duration of chest tube (P < 0.007) and length of hospital stay
      (P < 0.04) were significantly lower in the water seal group. In the air leak
      group (n = 31), 7 (23%) patients were managed with water seal and 24 (77%)
      patients with suction. Both duration of chest tube (P = 0.001) and length of
      hospital stay (P < 0.05) were significantly lower in the water seal group. In
      patients without air leak, chest tubes should be managed with water seal
      following anatomical pulmonary resection, resulting in significantly shorter
      chest tube duration and hospital length of stay.

PMID- 15986974
TI  - Percutaneous endoscopic gastrostomy in ICU patients with previous laparotomy.
AB  - To our knowledge, there is an absence of data evaluating the safety and efficacy
      of percutaneous endoscopic gastrostomy (PEG) placement in ICU patients with
      previous abdominal surgery. Our goals were to determine the complication rate of
      PEG in ICU patients who either had a recent or prior laparotomy compared to
      patients without any prior abdominal surgery. Prospective data was collected on
      42 consecutive patients with prior abdominal surgery who underwent PEG placement
      in a university ICU setting during a 3-year period. These patients were further
      stratified by time of previous abdominal surgery: recent = abdominal surgery
      during the current hospitalization; old = abdominal surgery done prior to the
      current hospitalization and >30 days. Complications were defined as technical
      problems, local infection, tube dislodgment, and bleeding. This data was compared
      to results of 75 consecutive PEG placements in ICU patients with no previous
      abdominal surgery (NPAS) at the same institution. A total of 117 patients were
      included in the study. Sixty-two (58%) of the patients were trauma patients and
      45 (42%) had other pathology. The mean age of the study population was 53 +/- 15
      years and they were primarily male (75%). The overall complication rates were as
      follows: local wound = 18.7 per cent, technical problems = 4 per cent, PEG
      dislodgment = 7.4 per cent, and bleeding = 3 per cent. Of the 42 patients with
      prior abdominal surgery, 22 were recent, and 20 were old. Local wound
      complications were the most common complication when stratified by PEG category
      (virgin = 17.3%, recent = 18%, and old = 15%) followed by dislodgment (virgin =
      6.7%, recent = 9%, and old = 5%). There were no significant differences in
      complication rates when comparing specific complications by PEG category as
      analyzed by chi2 analysis. PEG should be considered in all patients with previous
      laparotomy in need for long-term enteral access.

PMID- 15986975
TI  - Age affects presenting symptoms of achalasia and outcomes after myotomy.
AB  - Older patients with achalasia presumably have had a longer, more indolent course
      than younger patients. This study was undertaken to determine the impact of
      patient age and duration of symptoms on symptom severity and outcome after Heller
      myotomy. Two hundred sixty-two patients (142 men and 120 women), of average age
      49 years +/- 17.7 (SD), have undergone laparoscopic Heller myotomy. Patients
      scored their symptoms using a Likert scale and subjectively rated their overall
      outcome. Data are presented as median, mean +/- SD, when appropriate. Follow-up
      is 25 months, 32 months +/- 28.7. Symptom severity scores improved after myotomy
      (P < 0.001 for all, paired Student's t test). Before myotomy, older patients had
      less dysphagia, regurgitation, choking, and chest pain (P < 0.05). Duration of
      preoperative symptoms did not correlate with frequency of symptoms. After
      myotomy, older patients had lower scores for dysphagia, chest pain, choking, and
      heartburn (P < 0.01); patients with prolonged durations of symptoms had lower
      dysphagia and choking scores. Neither age nor duration of symptoms had a
      significant effect on overall subjective outcomes. All patients should expect
      significant reductions in symptoms of achalasia following myotomy. Age and
      duration of symptoms impact symptoms before and after myotomy, but neither seem
      to impact subjective measure of outcome.

PMID- 15986976
TI  - A retroperitoneal bleed induced by enoxaparin therapy.
AB  - Retroperitoneal bleeding is one of the most serious, potentially lethal
      complications of anticoagulation therapy. Although well documented in fully
      heparinized and coumadinized patients, there are only few reports of life
      threatening hemorrhages in low-molecular-weight heparin (LMWH)-treated patients.
      We present a case of almost fatal spontaneous retroperitoneal bleeding in a 71
      year-old woman with pneumonia and acute coronary syndrome. After receiving
      combination therapy with Lovenox (enoxaparin), aspirin, and Plavix for 5 days,
      she developed acute hemorrhagic shock and possible intra-abdominal compartment
      syndrome. Urgent computed tomography scan of the abdomen and pelvis was performed
      and showed a left retroperitoneal hematoma. The patient's condition continued to
      deteriorate, which prompted emergent exploration. After evacuating 3 L of free
      blood from the peritoneal cavity, we managed to stabilize the patient. Our case
      of spontaneous retroperitoneal bleeding adds to the growing number of cases in
      which enoxaparin has been associated with severe bleeding. A high index of
      suspicion is necessary if the patient displays any of the signs and symptoms that
      suggest major hemorrhage. It appears that those at highest risk receive doses
      approaching 1 mg/kg subcutaneously every 12 hours, have renal impairment, are of
      advanced age, and receive concomitant medications that can affect hemostasis. On
      average, a retroperitoneal hematoma occurs within 5 days of therapy with
      enoxaparin. In high-risk patients, enoxaparin activity (anti-factor Xa) should be
      carefully monitored.

PMID- 15986977
TI  - The association between Chance fractures and intra-abdominal injuries revisited:
      a multicenter review.
AB  - The association between Chance fractures and intra-abdominal injuries is reported
      to be as high as 89 per cent. Because prior studies were small series or case
      reports, we conducted a multicenter review to learn the true association between
      Chance fractures and intra-abdominal injuries as well as diagnostic trends.
      Trauma registry data, medical records, and radiology reports from 7 trauma
      centers were used to characterize 79 trauma patients with Chance fractures.
      Initial methods of abdominal assessment were computed tomography (CT) scan (79%),
      clinical examination (16%), and diagnostic peritoneal lavage (DPL) (5%). Twenty
      six (33%) patients had intraabdominal injuries of which hollow viscus injuries
      predominated (22%). Twenty patients (25%) underwent laparotomy. The presence of
      an abdominal wall contusion and automobile restraint use were highly predictive
      of intra-abdominal injury and the need for laparotomy. The association between a
      Chance fracture and intra-abdominal injury is not as high as previously reported.
      CT scan has become the primary modality to assess the abdominal cavity of
      patients with Chance fractures, whereas the role of DPL has diminished.

PMID- 15986978
TI  - Preoperative evaluation of endoscopic ultrasonography and portography in
      selecting devascularization surgery for esophagogastric varices.
AB  - This study assesses the role of endoscopic ultrasonography (EUS) and portography
      in selection of mode of devascularization surgery for esophagogastric varices
      (EGV) in patients with portal hypertension and reports our experience in the
      treatment of EGV with modified devascularization surgery. Forty-two cirrhotic
      patients with EGV were treated with devascularization surgery for variceal
      hemorrhage. Preoperatively, percutaneous transhepatic portography (PTP) and EUS
      were used as the guiding mode for therapy of EGV. In addition to
      devascularization and splenectomy, esophageal transection (ET) was performed in
      26 patients with upward-flow varices (UFV), whereas 16 patients with downward
      flow varices (DFV) underwent proximal gastrectomy instead of ET. In both UFV and
      DFV groups, grade II of intramural varices and extramural collaterals were most
      commonly observed on EUS imaging. There was no significant difference of EUS
      grading between these two groups (P > 0.05). The incidence of postoperative
      complications, mortality, and recurrent varices were not significantly different
      between these two groups. The overall 5-year survival rate for UFV group was 69.2
      per cent, whereas that for the DFV group was 68.7 per cent (P > 0.05). Our study
      shows that devascularization surgery is highly effective for the prevention of
      recurrent bleeding from EGV, and it provides an alternative treatment modality.
      Combined PTP and EUS are very helpful in determining adequate modalities of
      devascularization surgery.

PMID- 15986979
TI  - A case of Cushing syndrome secondary to ectopic adrenocorticotropic hormone
      producing carcinoid of the duodenum.
AB  - Cushing syndrome caused by adrenocorticotropic hormone (ACTH) production from
      solid tumors can result in life-threatening hypercortisolemia. Ectopic ACTH
      production is most commonly associated with bronchial carcinoids and squamous
      cell carcinoma of the lung. We report a case of Cushing syndrome caused by
      ectopic ACTH production from a carcinoid of the duodenum. The patient presented
      to an outside hospital in hypertensive crisis and diabetic ketoacidosis. After
      stabilization, diagnostic studies including a serum cortisol level, and computed
      tomography (CT) scans of the head, chest, abdomen, and pelvis revealed
      hypercortisolemia and a large mass in the head of the pancreas.
      Pancreaticoduodenectomy was performed. Pathologic investigation revealed a 1-cm
      carcinoid of the duodenum with two large metastatic lymph nodes near the head of
      the pancreas. This is the first reported case in the English literature of
      Cushing syndrome caused by ectopic ACTH production from a carcinoid of the
      duodenum.

PMID- 15986980
TI  - Extended right hepatectomy with total caudate lobe resection and biliary tree
      resection for a large colorectal liver metastasis involving both the right and
      left hepatic lobes and the umbilical fissure: a case report.
AB  - Very large right-sided liver tumors may grow up to the base of the umbilical
      fissure and involve the left hepatic duct and can occasionally reach the bile
      duct confluence. This kind of involvement has often been considered a
      contraindication to resection. We report a patient who presented with a large
      hepatic metastasis from colorectal cancer that reached the umbilical fissure and
      involved the left hepatic duct just above the bile duct confluence. An extended
      right hepatectomy including complete resection of caudate lobe was performed. We
      resected the left and common hepatic ducts, as well as both the entire hepatic
      and the proximal third of common bile duct. A long jejunal limb Roux-en-Y (45 cm)
      single-layer left intrahepatic hepaticojejunostomy was constructed. She is still
      well 14 months postoperatively. To the best of our knowledge, this is the first
      report of such a procedure employed for the treatment of a liver metastasis from
      colorectal cancer. Extended right hepatectomy including complete caudate lobe
      resection can be feasible even when the majority of the extrahepatic biliary
      system needs to be resected. Our approach probably offers the only chance to
      prevent early death from liver failure in these patients.

PMID- 15986981
TI  - Laparoscopic resection of periaortic paragangliomas.
AB  - Paragangliomas are extra-adrenal pheochromocytomas that are often located in the
      retroperitoneum along the aorta. Although laparoscopic resection is recommended
      for adrenal pheochromocytomas, few laparoscopic resections for paragangliomas
      have been reported. We describe the presentation and imaging findings of four
      patients with periarotic paraganglioma. Laparoscopic resection was successfully
      performed in three of the four patients; the fourth patient required conversion
      to an open procedure. This report adds to a growing number of cases documenting
      that laparoscopic resection of paragangliomas is safe and feasible.

PMID- 15986982
TI  - A new complication from a new technology: what a general surgeon should know
      about wireless capsule endoscopy.
AB  - Wireless capsule endoscopy has revolutionized the diagnostic evaluation of the
      small intestine and is increasingly used by gastroenterologists. However,
      complications can occur with this seemingly safe procedure. We report two cases
      of Crohn's disease in which capsule endoscopy was performed with retention of the
      capsules. Both patients were taken to the operating room electively after careful
      preoperative planning to address both the surgical aspect of Crohn's disease and
      the retained capsule. We reviewed the literature on the use of wireless capsule
      endoscopy in patients with Crohn's disease and discuss the approach to a new
      surgical complication.

PMID- 15986983
TI  - Sex differences in morbidity and mortality.
AB  - Women have worse self-rated health and more hospitalization episodes than men
      from early adolescence to late middle age, but are less likely to die at each
      age. We use 14 years of data from the U.S. National Health Interview Survey to
      examine this paradox. Our results indicate that the difference in self-assessed
      health between women and men can be entirely explained by differences in the
      distribution of the chronic conditions they face. This is not true, however, for
      hospital episodes and mortality. Men with several smoking-related conditions-
      including cardiovascular disease and certain lung disorders--are more likely to
      experience hospital episodes and to die than women who suffer from the same
      chronic conditions, implying that men may experience more-severe forms of these
      conditions. While some of the difference in mortality can be explained by
      differences in the distribution of chronic conditions, an equally large share can
      be attributed to the larger adverse effects of these conditions on male
      mortality. The greater effects of smoking-related conditions on men's health may
      be due to their higher rates of smoking throughout their lives.

PMID- 15986984
TI  - Race, gender, and marriage: destination selection during the Great Migration.
AB  - Using historical census microdata, we present a unique analysis of racial and
      gender disparities in destination selection and an exploration of hypotheses
      regarding tied migration in the historical context of the Great Migration. Black
      migrants were more likely to move to metropolitan areas and central cities
      throughout the period, while white migrants were more likely to locate in
      nonmetropolitan and farm destinations. Gender differences were largely dependent
      on marital status. Consistent with the "tied-migration" thesis, married women had
      destination outcomes that were similar to those of men, whereas single women had
      a greater propensity to reside in metropolitan locations where economic
      opportunities for women were more plentiful.

PMID- 15986985
TI  - Three dimensions of the survival curve: horizontalization, verticalization, and
      longevity extension.
AB  - Three dimensions of the survival curve have been developed: (1)
      "horizontalization," which corresponds to how long a cohort and how many
      survivors can live before aging-related deaths significantly decrease the
      proportion of survivors; (2) "verticalization," which corresponds to how
      concentrated aging-related ("normal") deaths are around the modal age at death
      (M); and (3) "longevity extension," which corresponds to how far the highest
      normal life durations can exceed M. Our study shows that the degree of
      horizontalization increased relatively less than the degree of verticalization in
      Hong Kong from 1976 to 2001. After age normalization, the highest normal life
      durations moved closer to M, implying that the increase in human longevity is
      meeting some resistance.

PMID- 15986986
TI  - The age pattern of first-birth rates among U.S. women: the bimodal 1990s.
AB  - Between 1990 and 2002, the age pattern of Type I first-birth rates (i.e., the
      hazard of a first birth) among U.S. women was bimodal. This pattern, driven by
      changing differential fertility patterns among racial and ethnic groups, reached
      its apex at the mid-1990s and had almost vanished by the decade's end. Research
      on first-birth timing has tended to focus on Type II first-birth rates and
      therefore has failed to identify this larger, bimodal pattern. This article
      presents the benefits of using Type I rates, documents the emergence of the
      bimodal pattern via two new measures of bimodality, and uses a decomposition
      analysis to discuss the pattern's causes.

PMID- 15986987
TI  - Market transition, educational disparities, and family strategies in rural China:
      new evidence on gender stratification and development.
AB  - Two theoretical perspectives have dominated debates about the impact of
      development on gender stratification: modernization theory, which argues that
      gender inequalities decline with economic growth, and the "women in development"
      perspective, which argues that development may initially widen gender gaps.
      Analyzing cross-sectional surveys and time-series data from China, this article
      indicates the relevance of both perspectives: while girls' educational
      opportunities were clearly more responsive than boys' to better household
      economic circumstances, the era of market transition in the late 1970s and early
      1980s failed to accelerate and, in fact, may have temporarily slowed progress
      toward gender equity.

PMID- 15986988
TI  - Famine, social disruption, and involuntary fetal loss: evidence from Chinese
      survey data.
AB  - Relying on half a million pregnancy histories collected from Chinese women in the
      late 1980s, we studied nearly a quarter century of self-reported miscarriages and
      stillbirths in China. Our results suggest that these two forms of involuntary
      fetal loss are affected not only by biological and demographic factors, such as
      the mother's age, pregnancy order, and pregnancy history, but also by the
      mother's social characteristics and the larger social environment. In this
      article, we focus on how two social and economic crises--the Great Leap Forward
      famine and the Cultural Revolution--resulted in elevated risks of miscarriage and
      stillbirth in the Chinese population.

PMID- 15986989
TI  - Ethnic intermarriage in times of social change: the case of Latvia.
AB  - We gain insight into the dynamics of ethnic intermarriage in times of social
      change by studying marriages between Latvians and Russians (including
      Belarussians and Ukrainians) that occurred in Latvia before and after
      independence from the Soviet Union. Before independence, ethnic intermarriage was
      already rather common, involving about 17% of the marriages annually. Since
      independence, intermarriage between Russians and Latvians has increased
      substantially. Part of this increase can be explained by selective emigration,
      but at least half of it may be due to integrative processes. Although there were
      more marriages between Russian men and Latvian women before independence, the
      gender pattern reversed after independence. Intermarriage levels were the highest
      among the less educated, children of mixed couples, partners with similar
      educational levels, and people in the countryside.

PMID- 15986990
TI  - Migration and relationship power among Mexican women.
AB  - Our study drew on original data collected in Durham, NC, and four sending
      communities in Mexico to examine differences in women's relationship power that
      are associated with migration and residence in the United States. We analyzed the
      personal, relationship, and social resources that condition the association
      between migration and women's power and the usefulness of the Relationship
      Control Scale (RCS) for capturing these effects. We found support for
      perspectives that emphasize that migration may simultaneously mitigate and
      reinforce gender inequities. Relative to their nonmigrant peers, Mexican women in
      the United States average higher emotional consonance with their partners, but
      lower relationship control and sexual negotiation power. Methodologically, we
      found that the RCS is internally valid and useful for measuring the impact of
      resources on women's power. However, the scale appears to combine diverse
      dimensions of relationship power that were differentially related to migration in
      our study.

PMID- 15986992
TI  - Changes in children's time with parents: a correction.
AB  - This article provides corrected estimates of the weekly time that 3- to 12-year
      old children spent either directly engaged with their parents or with their
      parents accessible to them in 1997, replicating the figures presented in the
      original 2001 Demography article. The data come from the 1997 Child Development
      Supplement to the Panel Study of Income Dynamics. The results show a considerably
      greater increase in children's total time in 1997 with mothers, fathers, or
      either parent than was shown in the original article. Some alternative estimates,
      likely reasons for the larger change, and the implications are discussed.

PMID- 15986991
TI  - By what measure? Family time devoted to children in the United States.
AB  - We argue that previous research on time devoted to child care has paid
      insufficient attention to the conceptualization of care time. Three separate
      problems are evident. First, the conventional focus on explicit activities with
      children distracts attention from the larger responsibilities of "passive" care,
      which ranges from time when children are sleeping to time when they are in the
      same general area but are not engaged in an activity with parents. Second, the
      empirical analysis of activity time focuses almost exclusively on parents,
      overlooking the role of relatives such as grandmothers and siblings. Third, the
      measurement of active care time often ignores the impact of overlaps among both
      care providers and recipients. Our analysis of the Child Development Supplement
      of the Panel Study of Income Dynamics sheds light on these three problems and
      presents new measures of passive and active care time.

PMID- 15986993
TI  - Food (miles) for thought--energy balance for locally-grown versus imported apple
      fruit.
AB  - This commentary compares the primary energy requirement for apples (cultivar
      'Braeburn'), which were either imported or locally-grown in Meckenheim, Germany.
      Imported apples of the same cultivar were grown in a Southern hemisphere winter
      in Nelson, Southland, New Zealand, and were picked at the end of March with
      subsequent 28 d transport by sea for sale in April in Germany. Locally-grown
      apples (cultivar 'Braeburn') were picked in mid-October and required a primary
      energy of nearly 6 MJ/kg of fruit including 0.8 MJoule/kg for five months CA
      storage at 1 degrees C during a Northern hemisphere winter until mid-March. This
      compared favourably with 7.5 MJoule/kg for overseas shipment from New Zealand,
      i.e. a ca. 27% greater energy requirement for these imported fruits. Overall, the
      primary energy requirement of regional produce, stored several months on-site,
      partially compensated for the larger energy required to import fresh fruit from
      overseas. This result is in marked contrast to reported overestimates of a
      reported up to 8-fold energy requirement for domestic versus imported apple juice
      concentrate. Our own findings of less primary energy required for domestic apple
      fruit is discussed with respect to providing local employment, fruit orchards
      preserving the countryside, quality assurance systems for local fruit such as QS
      and EUREP-GAP, networking and other factors favouring regional production.

PMID- 15986994
TI  - Green chemistry--views and strategies.
AB  - BACKGROUND AND GOAL: The object of Green Chemistry is the reduction of chemical
      pollutants flowing to the environment. The Chemistry and the Environment Division
      of EuCheMS has assumed Green Chemistry as one of its areas of interest, but one
      question to solve is where Green Chemistry should be placed within the context of
      Chemistry and the Environment. The concept of Green Chemistry, as primarily
      conceived by Paul Anastas and John Warner, is commonly presented through the
      Twelve Principles of Green Chemistry. However, these Twelve Principles, though
      fruit of a great intuition and common sense, do not provide a clear connection
      between aims, concepts, and related research areas of Green Chemistry. These two
      unsolved questions are the object of the present article. DISCUSSION: Green
      Chemistry is here placed as a part of Chemistry for the Environment, concerning
      the still non-existent pollutants. Indeed, the object of Green Chemistry is the
      reduction of pollution and risks by chemicals by avoiding their generation or
      their introduction into the biosphere. The distinction between pollutant
      chemicals and dangerous chemicals, along with the consideration of the exhaustion
      of fossil resources and the acknowledgement of the harmful effects of the
      chemicals employed in a great variety of activities, leads to the recognition of
      four general objectives for Green Chemistry. In order to accomplish these general
      objectives, a number of strategies, or secondary objectives and some fundamental
      concepts, namely, atomic economy, selectivity, potential harm or historical harm
      can be visualized. A connection is finally established between the strategies and
      current and future research areas of Green Chemistry. CONCLUSION: The ultimate
      aim of green chemistry is to entirely cut down the stream of chemicals pouring
      into the environment. This aim seems unattainable at present, but progress in the
      green chemical research areas and their application through successive approaches
      will certainly provide safer specialty chemicals and much more satisfactory
      processes for the chemical industry.

PMID- 15986995
TI  - A simple field method to determine mercury volatilization from soils.
AB  - BACKGROUND: Estimations of gaseous mercury volatilization from soils are often
      complex, stationary and expensive. Our objective was to develop a mobile and more
      simple, easy to handle and more cost-effective field method allowing rapid
      estimates of potential Hg emissions from soils. METHODS: The study site is
      located in Germany, about 100 kilometers south-westerly of Berlin and influenced
      by the river Elbe and its tributary Saale river. The site is representative for a
      lot of other floodplain locations at the river Elbe and highly polluted with Hg
      and other heavy metals. For our study we developed a system consisting of a glass
      chamber gas, two gold traps, a battery operated pump and a gas meter. Adsorbed
      total gaseous mercury (TGM) in the gold traps was determined by use of atomic
      absorption spectrometry (AAS). RESULTS AND DISCUSSION: In contrast to the common
      used flux chambers we designed a chamber without inlet and named it gas suck up
      chamber (GSC). TGM fluxes determined with the GSC showed a very close linear
      correlation (r = 0.993) between the TGM content in the gold traps and the
      corresponding pumped gas volume. The TGM adsorbed, increased proportional with
      increasing gas volume indicating homogenous concentrations of gaseous mercury in
      the soil air sucked. In contrast to the commonly used dynamic flux chamber with
      the aim of precisely measuring actual fluxes of Hg from a defined soil area, we
      focused on developing of a measurement system which will allow rapid estimates of
      potential Hg emissions of a site. Earlier research at the study site indicated a
      high potential for releasing volatile Hg from the soil to the atmosphere. Indeed,
      due to the high Hg content of the soil significant amounts of TGM could be
      detected and no shortage was reached. CONCLUSION: Our initial measurements are
      still too few in number neither to generalize the achieved results nor discuss
      controlling factors and processes. However, we are pleased to communicate that
      the developed GSC is well suited to become an effective sampling set up to
      rapidly estimate the magnitude of Hg volatilization from soils. OUTLOOK: Further
      measurements at other polluted locations are necessary to verify the GSC method.
      In addition the use of a mercury analyzer instead of gold traps is planned for
      faster risk assessments.

PMID- 15986996
TI  - Toxic effects of crude oil combined with oil cleaner simple green on yolk-sac
      larvae and adult rainbow trout Oncorhynchus mykiss.
AB  - BACKGROUND, GOAL AND SCOPE: Cleaner CRYSTAL Simple Green (SG) was used for the
      cleanup of the oil spill in the Baltic Sea near Lithuania in 2001. No scientific
      data are available on the effects and consequences of its application for local
      aquatic life. The aim of this study was to determine and compare sublethal
      effects of a) solution SG; b) crude oil alone; c) SG in combination with oil on
      rainbow trout Oncorhynchus mykiss at different stages of its development in
      laboratory conditions. METHODS: Laboratory studies were performed on adult
      rainbow trout (4-day duration) and on yolk-sac larvae (25-day duration)
      evaluating their biological parameters. Concentrations of water-soluble and thin
      dispersed fractions of petroleum hydrocarbons were measured using gas
      chromatography. RESULTS AND DISCUSSION: SG solution (0.5 mg/l) did not affect the
      survival of larvae and adult fish, and no significant changes were determined in
      respiratory parameters of the exposed lar vae and adult fish. The most expressed
      alterations were found in morphological parameters (a decrease in the average
      body mass) of larvae and in haematological indices (a decrease in the leukocyte
      count) of adult fish at the end of the tests. Crude oil (1610 mg/l) did not
      affect the survival of adult fish during the 4-day exposure. An increase in
      larvae mortality rate (approximately 36%) was recorded at the end of the tests. A
      significant decrease in the average body mass and heart rate of larvae as well as
      in gill ventilation frequency of larvae and adult fish were determined. SG
      combined with oil induced an increase in larval mortality approximately 46% of
      individuals died at the end of the tests. No mortality was recorded in adult
      fish. The average body mass and heart rate of larvae were significantly
      decreased. Marked changes were also found in respiratory parameters (gill
      ventilation frequency of larvae and adult fish significantly decreased, while
      'coughing' rate increased). A 1-day, 2-day exposure of fish to SG combined with
      oil induced a significant decrease in the leukocyte count of adult fish, which
      was also determined at the end of the tests. The augmentation of adverse impact
      could be explained by the data obtained from our studies. When SG was added into
      dilution water with crude oil the concentration of petroleum hydrocarbons in the
      mixture increased 3 approximately 4.5 times after 24 h and 96 h, respectively.
      CONCLUSIONS: The comparative study of the effects of crude oil alone, SG and SG
      combined with oil showed that their toxic effects on fish differed. Oil combined
      with SG was found to be more toxic to fish (larvae and adults) than SG alone and
      oil alone. Fish at early stages of development (yolk-sac larvae) were more
      sensitive to the effects of the compounds studied than adults. RECOMMENDATIONS
      AND OUTLOOK: To diminish the negative impact of oil spill cleanup using chemicals
      on aquatic ecosystems, it is recommended to carry out more comprehensive studies
      of their effects and after-effects in laboratory conditions using a wide scale of
      local aquatic organisms. The selected species of the most sensitive aquatic
      organisms should include those which are unable to escape the impact of combined
      action of oil and cleaners. Special attention should be directed to the research
      of effects of these pollutants on studied organisms at their most sensitive
      stages of life (reproduction, hatching, early stages of development), as after
      effects of exposure to pollutants may be observed in future generations.

PMID- 15986997
TI  - Ethoxyresorufin-O-deethylase (EROD) activity in dab (Limanda limanda) as
      biomarker for marine monitoring.
AB  - GOAL, SCOPE AND BACKGROUND: Ethoxyresorufin-O-deethylase (EROD) is a well
      accepted marker for biological effects in fish and is, therefore, part of
      numerous monitoring programmes. EROD activity was measured in livers of dab
      (Limanda limanda) from the German Bight (North Sea) from 1995 to 2003. The aim of
      the present long-term study was (a) time trend monitoring of EROD activity of dab
      from the German Bight and (b) to elucidate the needs for a successful application
      of EROD activity as an early warning system. METHODS: EROD activities were
      determined fluorimetrically in dab liver microsomes, using resorufin as an
      external standard. The limit of detection (LD) and the limit of quantification
      (LQ) were calculated. Results were referred to protein concentrations. RESULTS
      AND DISCUSSION: EROD activities of 610 female dab caught in different seasons
      between January 1995 and August 2003 were analyzed individually. Activities
      varied from < LD to 1768 pmol/(min mg protein) and showed an annual cycle as well
      as significant differences between the years. Highest EROD activities were
      observed in early summer and lowest activities during the winter period. In
      autumn 2002, significantly elevated EROD activities were detected, possibly
      related to effects of the River Elbe flood event. Two scenarios with different
      EROD baseline data are presented to discuss the prerequisites for the use of EROD
      as a monitoring tool. The comparison of these scenarios underlines the importance
      of appropriate season-specific baseline data. CONCLUSION: The use of EROD as an
      early warning tool for contaminant effects in dab in the German Bight has
      different prospects during the year, because, due to the high background
      variability, elevated EROD activities are less easy to detect in spring/ summer
      than during the remaining times of the year. RECOMMENDATION AND OUTLOOK: The
      availability of site-specific data on the EROD baseline level, its random
      variation and its annual cycle is a necessary prerequisite for monitoring. If
      monitoring is to be carried out only for a limited time period of the year, a
      season with low background variability in EROD activity (autumn) should be chosen
      to avoid the need for a compensation of the temperature-triggered shift in sexual
      cycles and the resulting changes in EROD activity.

PMID- 15986998
TI  - Phytoplankton community and chlorophyll a as trophic state indices of Lake Skadar
      (Montenegro, Balkan).
AB  - BACKGROUND, AIMS AND SCOPE: Phytoplankton, as a first step in trophic cascades of
      lakes, can be a good indicator of trophic states, considering that every
      environmental change affects this community and many species of this community
      are sensitive to changes, and that they response very quickly. In this study, we
      tried to assess and predict the trophic state of Lake Skadar according to
      phytoplankton data. METHODS: Water samples were collected using Ruttner sampling
      bottle. Temperature, dissolved oxygen, ph, conductivity and transparence were
      measured in situ using portable equipment. Nutrients and chlorophyll a were
      measured using standard spectrophotometric methods. A determination of
      phytoplankton species was performed using relevant keys and the counting of cells
      was performed using sedimentation methods. RESULTS AND DISCUSSION: The species
      composition of Lake Skadar revealed 95 taxa, with Chlorophyceae and
      Bacillariophyceae being represented best. According to an average chlorophyll a
      concentration of 5.9 pg/l, Lake Skadar belongs to the mesotrophic level of the
      trophic scale. Developed prediction equation for chlorophyll a revealed a good
      prediction (R2 = 0.71) and the parameter Secchi depth was primarily correlated
      with chlorophyll a concentration. Trophic state indices derived from chlorophyll
      a and transparency, were close together, but both were below the phosphorous
      index. Values of trophic state indices rank the Lake Skadar as being mesotrophic.
      This study also showed that indices of diversity based on phytoplankton are weak
      indicators of trophic status and that they can well characterize only differences
      between assemblages and associations. According to calculated saprobic indices
      (ranging from 1.5 to 2.15), Lake Skadar is on betamesosaprobic level of
      saprobity, which means that it is moderately polluted with organic compounds.
      CONCLUSIONS: Total phosphorus is not the main limiting factor for the
      phytoplankton community in Lake Skadar. Disagreements between chlorophyll and the
      transparency index, on the one hand, and the total phosphorus index, on the
      other, suggest that the phytoplankton in Lake Skadar is probably limited by other
      factors than phosphorus, such as nitrogen, toxic substances or intense
      zooplankton grazing. According to the majority of investigated parameters and
      indices derived from phytoplankton data, Lake Skadar is mesotrophic, with
      tendencies toward eutrophic levels during the summer period. RECOMMENDATIONS AND
      OUTLOOK: Long-term monitoring is required for a better estimation of state and
      the conditions of Lake Skadar. Further studies on factors influencing the
      phytoplankton community, especially zooplankton grazing and toxic substances,
      which were not included in this study, should be continued in the future to
      improve the efficiency of phytoplankton usage in estimating the ecological and
      trophic conditions of Lake Skadar.

PMID- 15986999
TI  - AOX formation and elimination in the oxidative treatment of synthetic wastewaters
      in a UV-free surface reactor.
AB  - INTENTION, GOAL, SCOPE, BACKGROUND: The effect of chloride concentration and pH
      on the UV oxidation systems was examined. Phenol and methanol were used as
      organic substances. The treatment of these chemicals by UV oxidation using a
      newly developed lab scale pretest UV-Free Surface Reactor (UV-FSR) with and
      without Cl- addition at different pH values, is evaluated. Results of this study
      indicated that the Cl- concentration of the water and the chemical structure of
      the substances is more important than the pH of the water. There was no AOX at
      the beginning of the experiments, but a de-novo synthesis of AOX was observed
      during the batch experiments. This is caused by the high chloride content of the
      wastewaters. It can be supposed that OH-radicals oxidize some chloride-ions to
      form chlorine, which further reacts with organic compounds. During the treatment,
      these AOX compounds which are produced from the beginning of the reaction are
      destroyed again. Evaluations of these experiments were done according to TOC and
      AOX results. Approximately 80% and 99% TOC removal efficiencies were obtained for
      the treatment of Phenol and Methanol-containing wastewaters, respectively.
      OBJECTIVE: In the literature, there are no relevant publications concerning the
      AOX formation of wastewater by wet oxidation-iron catalysed or by application of
      UV. For that reason, the main objectives of this study were: 1. to see the
      influence of chloride concentration and pH on the AOX(de.novo) formation with
      newly developed UV-Free Surface Reactor (UV-FSR), 2. to make a comparison of
      different AOPs, 3. to observe the effect of the chloride concentration on the TOC
      degradation efficiency, 4. to optimise reaction conditions. METHODS: In synthetic
      wastewaters, Methanol (CH3OH) and Phenol (C6H5 OH) are used as pollutants. The
      concentration of each substance was 1000 mg/l and COD values were calculated
      theoretically. The H2O2 addition was calculated according to the COD with a
      convenient stoichiometric factor (e.g. 1). During experiments, the pH was always
      kept constant with the addition of either 25% H2SO4 or 33% NaOH depending on the
      experimental conditions. Each substance was treated with the addition of 1000
      mg/l Cl-, 10000 mg/l Cl- and without Cl- addition at pH 3, pH 7 and pH 10,
      respectively. NaCl was used as a Cl- source. Adsorbable Organic Halogenides (AOX)
      were determined using a TOX analyser (European Standard EN 1485 H 14, 1996). TOC
      measurements were carried out using an Elementar High TOC Analyzer equipped with
      an auto sampler. The H2O2 concentration was measured according to German Standard
      Methods (DIN 38409, Part 15, 1987). RESULTS AND DISCUSSION: The first step was to
      determine the effect of pH on the AOX formation in the process. Therefore,
      experiments were carried out at three different pHs: acidic (pH 3), neutral (pH
      7) and basic (pH 10) conditions at a constant initial Methanol concentration of
      1000 mg/l and a hydrogen peroxide concentration of 3185 mg/l (1 x
      stoichiometric). All results were evaluated according to applied pH. At these
      conditions, the amount of H2O2 (53 ml/10 l) concentration was nearly zero after 1
      hour batch treatment of Methanol. There was no AOX at the beginning of the
      experiments, but the AOX value increased after 6-18 min. At the end of 1 hour
      batch treatment this produced AOX was treated again. The maximum AOX production
      was obtained with the addition of 10000 mg/l Cl-, whereas there is no AOX
      production during the experiment when Clwas not used. In all studies, however,
      TOC values decreased to almost zero after 1 hour batch treatment. After the
      experiments with Methanol, Phenol treatment was carried out at different pHs as a
      second experiment. pH was kept constant with the addition of either H2SO4 or NaOH
      depending on the experimental conditions. During experiments with Phenol, the
      colour of the water changed from colourless to a yellowish-red. After 1 hour
      treatment, the colour of the water was red. Therefore, these experiments were
      continued until the water became colourless again, and this took about 5 hours.
      Although there was no AOX at the beginning of the experiments, it increased after
      30 min to 1 hour oxidation with the addition of 1000 mg/l Cl- and 10000 mg/l Cl-.
      There was no AOX production during the experiments when CI- was not added. At the
      end of 5 hours of treatment, formed AOX was degraded and the TOC concentration
      decreased from 766 mg/l to approximately 200 mg/l. CONCLUSION: These experiments
      of this study showed that the effects of Cl- concentration of the water and the
      chemical structure of the substances is more than that of the pH on the AOX
      formation. During the batch experiments, a de-novo synthesis of AOX was observed
      very impressively due to the high chloride content of the wastewaters. It can be
      implied that OH-radicals oxidize some chloride-ions to form chlorine, which
      further reacts with organic compounds so that AOX(de novo) is formed. At the end
      of the reaction times these AOX compounds are also destroyed. RECOMMENDATION AND
      OUTLOOK: It is more cost effective to use these processes for only purposes such
      as toxicity reduction, enhancement of biodegradability, decolourisation and
      removal of micropollutants. However, the most important point is the optimization
      of the reaction conditions for the process of concern. The AOP applied can be
      used, for instance, for AOX reduction and TOC removal of industrial wastewaters.

PMID- 15987000
TI  - Time series of metals in mosses and their correlation with selected sampling site
      specific and ecoregional characteristics in Germany.
AB  - GOAL, SCOPE AND BACKGROUND: The UNECE Heavy Metals in Mosses Surveys provide
      exposure data (Predicted Environmental Concentrations--PEC) for ecotoxicological
      risk assessments by measuring the accumulation of several metals in naturally
      growing mosses throughout Europe. Germany took part in the monitoring campaigns
      1990, 1995 and 2000. The article deals with the description and application of
      the extensive methodical design developed to investigate the following three
      hypotheses: 1. The metal accumulation in mosses measured at up to 1000 sites may
      be geostatistically extrapolated from the sampling sites to ecoregions in order
      to transform the site-specific PEC values to surface PEC values. 2. The metal
      specific measurement values may be aggregated to metals integrating accumulation
      indices. 3. The ecoregional situation as well as sampling site-specific
      topographical features such as altitude, slope gradient or direction influence
      the accumulation of metals in mosses. METHODS: The methodical design integrates
      several data sources as well as statistical analysis and GIS techniques: The site
      specific data on metal accumulation are geostatistically transformed to valid
      surface data on metal accumulation. The sampling site-specific measurement data
      and the estimated surface data on the accumulation of As, Cd, Cr, Cu, Fe, Hg, Ni,
      Pb, Sb, Ti, V and Zn are aggregated to integrative metal accumulation indices by
      means of percentile statistics. The metal-specific estimated data and the metals
      integrating accumulation indices are correlated with site-specific data on
      altitude, slope gradient and direction as well as with the ecoregional conditions
      derived from a multivariate ecoregionalisation. The mean multi-metal accumulation
      index for the whole of Germany over the ten year period from 1990 to 2000 was
      related to the accumulation indices within each of the ecoregions and each of the
      monitoring campaigns 1990, 1995 and 2000. In addition to this ecoregionalisation
      of the temporal trends of metal accumulation, the hot spots of accumulation are
      mapped. RESULTS AND DISCUSSION: The Heavy Metals in Mosses Survey 2000 reveals
      low metal concentrations in most European countries. In Germany, all metals
      decreased about 22% (Cu) to 64% (Pb) from 1990 to 2000. Mapping concentrations as
      dot maps deliver the most unbiased and detailed picture of the spatial structure
      of the metal accumulation in mosses. This information, detailed with respect to
      metal species and sampling site, is spatially generalized by means of
      geostatistical estimation. According to the cross-validation, the precision of
      the geostatistical estimation is quite good so that the extrapolation does not
      bias the spatial structure, but helps to clarify it. By percentile statistics, an
      ordinally scaled multi-metal accumulation index is calculated and spatially
      differentiated over time in terms of ecoregions which were calculated by means of
      Classification and Regression Trees (CART). The integrative statistical analysis
      reveals declinations of up to 80% of the multi-metal accumulation in some of
      Germany's ecoregions from 1990 to 2000. CONCLUSION: The monitoring of heavy metal
      bioaccumulation by means of mosses is an effective and cheap method for the
      analysis of the environmental concentrations of metals accumulated in terrestrial
      ecosystems. Geostatistics, percentile statistics, cross-tabulations and
      ecoregionalisation serve well to clarify the spatial and temporal trends in the
      large data sets coming out of the UNECE Heavy Metals in Mosses Surveys: By
      combining these statistical methods and integrating them into a geographical
      information system (GIS), they allow to detect and map the spatial-temporal
      trends of metal accumulation, to calculate metal-integrating accumulation
      indices, to describe temporal trends of metal accumulation within ecoregions, and
      to detect and map hot spots. RECOMMENDATION AND PERSPECTIVE: The spatial and
      temporal trends of metal accumulation in mosses should be linked with deposition
      data and data on the vitality of forest ecosystems, as well as with data on human
      health. Statistical valid interspecies calibration is needed. The integrated
      methodology of data evaluation presented in the article at hand should be
      implemented in the future UNECE Heavy Metals in Mosses Surveys. The hot spot
      areas should be investigated with special care in the 2005 survey to prove if the
      PEC values of the metals exceed the Predicted no Effect Concentrations (PNEC
      values). In addition to the metals, the 2005 survey should monitor the nitrogen
      accumulation in mosses.

PMID- 15987002
TI  - Life cycle assessment as part of sustainability assessment for chemicals.
AB  - BACKGROUND: LCA is the only internationally standardized environmental assessment
      tool (ISO 14040-43) for product systems, including services and processes. The
      analysis is done 'from cradle-to-grave', i.e. over the whole life cycle. LCA is
      essentially a comparative method: different systems fulfilling the same function
      (serving the same purpose) are compared on the basis of a 'functional unit'--a
      quantitative measure of this function or purpose. It is often believed that LCA
      can be used for judging the (relative) sustainability of product systems. This is
      only partly true, however, since LCA is restricted to the environmental part of
      the triad 'environment/ecology--economy--social aspects (including
      intergenerational fairness)' which constitutes sustainability. Standardized
      assessment tools for the second and the third pillar are still lacking, but Life
      Cycle Costing (LCC) seems to be a promising candidate for the economic part.
      Social Life Cycle Assessment still has to be developed on the basis of known
      social indicators. METHOD AND LIMITATIONS: LCA is most frequently used for the
      comparative assessment or optimization analysis of final products. Materials and
      chemicals are difficult to analyse from cradle-to-grave, since they are used in
      many, often innumerable product systems, which all would have to be studied in
      detail to give a complete LCA of a particular material or substance! This
      complete analysis of a material or chemical is evidently only possible in such
      cases where one main application exists. But even if one main application does
      exist, e.g. in the case of surfactants (chemicals) and detergents (final
      products), the latter may exist in a great abundance of compositions. Therefore,
      chemicals and materials are better analysed 'from cradle-to-factory gate',
      leaving the analysis of the final product(s), the use phase and the 'end-of-life'
      phases to specific, full LCAs. CONCLUSION: A comparative assessment of production
      processes is possible; if the chemicals (the same is true for materials) produced
      by different methods have exactly the same properties. In this case, the
      downstream phases may be considered as a 'black box' and left out of the
      assessment. Such truncated LCAs can be used for environmental comparisons, but
      less so for the (environmental) optimization analysis of a specific chemical: the
      phases considered as 'black box' and left out may actually be the dominant ones.
      A sustainability assessment should be performed at the product level and contain
      the results of LCC and social assessments. Equal and consistent system boundaries
      will have to be used for these life cycle tools which only together can fulfil
      the aim of assessing the sustainability of product systems.

PMID- 15987001
TI  - Distribution and fractionation of copper in soils of apple orchards.
AB  - BACKGROUND: Frequent application of Bordeaux mixture, which includes copper, as a
      fungicide in fruit and grape orchards may lead to copper accumulation in the
      soil, especially when orchard age and application times increase. The objectives
      of this study were: (i) to investigate the copper content and its spatial
      distribution in orchard soils; (ii) to identify the copper fractionation in soil
      and its relationship with plant uptake; (iii) to understand the characteristics
      of copper contamination in orchard soils. MATERIALS AND METHODS: Soil profile
      samples were taken in apple orchards with ages of 0, 5, 10, 20, 30 years and pot
      experiments were also carried out to study the effects of external copper input
      on copper fractionation. All soil samples were air-dried, ground and extracted
      with 0.43 mol L(-1) HNO3 for the total absorbed copper. Fractionation
      determination was conducted following Tessier and Shuman sequential extraction
      methods, and copper was measured with AAS. Plant samples were first dry ashed,
      dissolved with 6 mol L(-1) HCI and then copper and other elements were measured
      with ICP-MS. RESULTS AND DISCUSSION: Soil total Cu was higher in the apple
      orchards than that in non-orchard fields and was seen to have increased with
      orchard age. Soil Cu increased substantially with the average annual copper
      increase, ranging from 2.5 to 9 mg Cu kg(-1). The distribution of copper in the
      soil profile was uneven, decreasing from surface to deeper layers, and the
      differences were significant, but the contents in every layer were also
      significantly correlated with those in the next layers. For all copper fractions,
      the organically bound, crystalline Mn oxide bound, and amorphous Fe bound
      fractions extracted with the Shuman method were much higher than the exchangeable
      and residual fractions. Using the Tessier method, organically bound, carbonate
      bound and Fe-Mn oxide bound fractions were much higher. With an increase in
      external copper input, the organically bound, crystalline Mn oxide bound and
      amorphous Fe bound fractions in the Shuman method and organically bound,
      carbonate bound and Fe-Mn oxide bound fractions in the Tessier method all
      increased significantly, while the changes in other fractions were not
      significant. Soil total copper and copper fractions were found to have good
      correlations with apple tree uptake. Copper in fruit flesh had significant
      correlations with soil total content in the 0-10 cm layer, all the copper
      fractions in the 0-5 cm layer, and some fractions in the deeper layers.
      CONCLUSION: Copper content in orchard soils increased significantly with
      intensive application of Bordeaux mixtures and orchard age. Copper content
      decreased sharply from the topsoil to deeper soil layers. The copper contents in
      different layers also significantly correlated with those in the next layers.
      Dominant fractions of the copper in soil were mainly associated with organic
      matter, iron and manganese oxides and carbonates. A close relationship was found
      between the copper content in soils and in apple tree organs (which contained 8.9
      to 66 mg kg(-1) Cu). RECOMMENDATION AND PERSPECTIVE: Though most copper in the
      soil was specifically adsorbed or immobilized, and copper was mainly distributed
      in topsoil, which was essentially devoid of roots, the copper concentration of
      fruit still had significantly positive correlations with soil copper and most
      copper fractions. Therefore, measures must be taken to control copper
      accumulation in orchard soils and to make the apple fruit production sustainable.

PMID- 15987003
TI  - What is the EuCheMS, Division of Chemistry and the Environment?

PMID- 15987004
TI  - School nurse perceptions of barriers and supports for children with diabetes.
AB  - Adolescents with type 1 diabetes are likely attending most middle and high
      schools. These youth often do not receive the support needed to manage their
      diabetes during or after school. Nurses (n=110) from 3 states responded to a
      survey examining perceptions of barriers to and supports for diabetes management
      during school and after school activities. Results indicated that adolescents
      need more support at school. Support could be facilitated by education of school
      staff; improved communication among youth, parents, school nurses, teachers, and
      physicians; and more communication from adolescents to others about what they
      need to manage well in school. Open-ended questions allowed nurses to provide
      recommendations for supporting youth and ideas for addressing barriers to
      management at school. Future studies should address ways to enable adolescents to
      communicate about their diabetes and ways to educate the school team.

PMID- 15987005
TI  - Perceptions of school toilets as a cause for irregular toilet habits among
      schoolchildren aged 6 to 16 years.
AB  - Irregular bladder and bowel habits can contribute to urinary and bowel problems.
      Schoolchildren undergoing treatment for these problems often do not follow the
      recommendation of regular toilet visits at school, claiming negative perceptions
      of school toilets. This study examined 6- to 16-year-old schoolchildren's
      perceptions of school toilets and whether the perceptions affect bladder and
      bowel habits at school Some 385 Swedish schoolchildren aged 6 to 16 years were
      surveyed using a semistructured questionnaire. Children aged 13 to 16 years had
      the most negative perceptions. Twenty-five percent (overall 16%) of older
      children reported never using the school toilet to urinate, and 80% (overall 63%)
      never used it to defecate. Perceptions of sight and smell and emotional
      constraints hindered children from using the school toilets. Children generally
      based their perceptions of school toilets on physical appearance, offensive
      smell, and feelings of insecurity. Children's perceptions affected their toilet
      habits and would rather endure physical discomfort than the psychological and
      social discomfort of using the school toilet. Children already suffering from
      urinary tract or intestinal problems face particular difficulties without regular
      toilet visits during the day.

PMID- 15987006
TI  - Effects of a nutrition education program on the dietary behavior and nutrition
      knowledge of second-grade and third-grade students.
AB  - This research investigated the effects of a nutrition education program on
      dietary behavior and nutrition knowledge among elementary school-aged children
      participating in a Social Cognitive Theory-based nutrition education program.
      Participants included 1100 second-grade and third-grade students selected by
      convenience-type sampling from public schools in Alabama. A preassessment and
      postassessment control group design assessed dietary behavior and nutrition
      knowledge using Pizza Please, a specially designed interactive evaluation tool. A
      2 x 2 mixed analysis of variance was used to analyze data. Children in the
      treatment group exhibited significantly (p < .001) greater improvement in overall
      dietary behaviors such as consumption of dairy products, fruits, and vegetables,
      than children in the control group. Children in the treatment group exhibited
      significantly (p < .001) greater improvement in nutrition knowledge, including
      Food Guide Pyramid understanding, nutrient-food association, and nutrient-job
      association, than children in the control group. Results suggest that nutrition
      education programs that teach positive dietary messages potentially can improve
      dietary behavior and increase nutrition knowledge in children.

PMID- 15987007
TI  - A cross-national comparison of school drug policies in Washington State, United
      States, and Victoria, Australia.
AB  - Using mail survey data collected from primary and secondary school administrators
      in Washington State, United States, and in Victoria, Australia, this study
      compared aspects of the school drug policy environment in the 2 states.
      Documented substance-use policies were prevalent in Washington and Victoria but
      less prevalent.in primary schools, especially in Victoria. Victorian school
      policy-setting processes were significantly more likely to involve teachers,
      parents, and students than processes in Washington schools. Consistent with
      expectations based on their respective national drug policy frameworks, school
      drug policies in Washington schools were more oriented toward total abstinence
      and more frequently enforced with harsh punishment (such as expulsion or calling
      law enforcement), whereas policies in Victorian schools were more reflective of
      harm-minimization principles. Within both states, however, schools more regularly
      used harsh punishment and remediation consequences for alcohol and illicit-drug
      violations compared to tobacco policy violations, which were treated more
      leniently.

PMID- 15987008
TI  - Charting your course using a seabag philosophy.

PMID- 15987009
TI  - An immunization education program for childcare providers.

PMID- 15987010
TI  - Whose life is it, anyway? The evolving face of euthanasia.

PMID- 15987011
TI  - Awareness and knowledge of diabetes in Chennai--the Chennai Urban Rural
      Epidemiology Study [CURES-9].
AB  - BACKGROUND AND AIM: There are virtually no epidemiological studies from India
      assessing the level of awareness of diabetes in a whole population. The aim of
      the present study was to assess the awareness of diabetes in an urban south
      Indian population in Chennai. METHODS: The Chennai Urban Rural Epidemiology Study
      (CURES) is an ongoing population based study conducted using a systematic
      sampling method on a representative population (aged > or = 20 years - 26001
      individuals) of Chennai [formerly Madras], the largest city in Southern India. A
      structured questionnaire was used to obtain information related to demography,
      education and medical history. The questionnaire included five questions on
      diabetes awareness. RESULTS: Of the total 26,001 individuals, only 75.5%
      (19642/26001) of the whole population reported that they knew about a condition
      called diabetes or conversely nearly 25% of the Chennai population was unaware of
      a condition called diabetes. 60.2% (15656/26001) of all participants and 76.7%
      (1173/1529) of the self reported diabetic subjects knew that the prevalence of
      diabetes was increasing in India. Only 22.2% (5764/ 26001) of the whole
      population and 41.0% (627/1529) of the known diabetic subjects were aware that
      diabetes could be prevented. Knowledge of the role of obesity and physical
      inactivity in producing diabetes was very low, with only 11.9% (3083/26001) of
      study subjects reporting these as risk factors for diabetes. Only 19.0%
      (4951/26001) of whole population knew that diabetes could cause complications.
      Even among the self reported diabetic subjects, only 40.6% (621/1529) were aware
      that diabetes could produce some complications. CONCLUSION: Awareness and
      knowledge regarding diabetes is still grossly inadequate in India. Massive
      diabetes education programmes are urgently needed both in urban and rural India.

PMID- 15987012
TI  - Clinical and etiological profile of hyperprolactinemia--data from a tertiary care
      centre.
AB  - OBJECTIVE: To study the clinical presentation and etiology of hyperprolactinemia,
      a common disorder encountered in endocrine practice. METHODS: We analyzed the
      clinical data, hormone profile and imaging reports of 187 females with documented
      hyperprolactinemia, over a period of 6 years (5 years retrospective analysis and
      one year prospective study). RESULTS: Majority of the 187 subjects studied
      presented in 3rd or 4th decade. Galactorrhoea was the commonest presenting
      symptom occurring in 159 subjects (85%), followed by amenorrhea in 68.9%; both
      amenorrhea and galactorrhea were seen in 45.4%. A microprolactinoma was
      demonstrated in 67 patients (35.8%), a nonfunctioning pituitary macroadenoma with
      stalk hyperprolactinemia occurred in 30 patients (16%) and polycystic ovarian
      disease was documented in 24 (12.8%). In 52 patients (27.8%) no apparent cause
      could be ascertained. CONCLUSIONS: Syndrome of amenorrhea and/or galactorrhea is
      the commonest presentation in hyperprolactinemia. Microprolactinoma was the most
      frequent identifiable etiology followed by idiopathic and stalk
      hyperprolactinemia in our series.

PMID- 15987013
TI  - Imatinib mesylate in chronic myeloid leukemia: a prospective, single arm, non
      randomized study.
AB  - Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder
      characterized by the balanced reciprocal translocation t (9:22). The resulting
      fusion gene, the BCR-ABL, is responsible for oncogenesis. Imatinib mesylate is a
      novel molecule, which inhibits the protein product of this fusion gene and hence
      has been used in the treatment of CML. The present study evaluates 174 patients
      with CML treated with imatinib mesylate. Of these 174 patients, 97 were in
      chronic phase, 47 in accelerated phase and 30 patients had blast crisis. Patients
      in chronic phase received imatinib mesylate in the dose of 400-mg daily, while
      those in accelerated phase and blast crisis received 600 to 800 mg daily. Of the
      97 patients with chronic phase, 49 patients (50.5%) achieved a major (major +
      complete) cytogenetic response. Of the 47 patients in accelerated phase, 10
      patients (21.3%) achieved a major cytogenetic response and in 30 patients with
      blast crisis, 7 (23.3%) achieved a major cytogenetic response. Dermatitis,
      mucositis, neutropenia and thrombocytopenia were some of the major toxicities. Of
      interest, 121 of the 174 patients (69.5%) developed generalized hypopigmentation.
      We conclude that imatinib mesylate is a safe and effective first-line therapy for
      chronic myeloid leukemia.

PMID- 15987014
TI  - Severe ST depression due to hypokalemia mimicking ischaemia.

PMID- 15987015
TI  - Dermatological toxicity of imatinib mesylate.

PMID- 15987016
TI  - Assessment of glycemia in diabetes mellitus: hemoglobin A1c.
AB  - The monitoring of glycemia is an essential component of diabetes care. It may be
      divided into self-monitoring of blood glucose (SMBG), which measures the
      immediate level of glycemia, and measurement of hemoglobin A1c (HbA1c), which
      reflects longer-term glycemia. SMBG was discussed in an earlier review. HbA1c is
      a measure of erythrocyte hemoglobin glycation, and since erythrocytes have about
      a 120 day life span, HbA1c reflects mean glycemia for the previous 3 months
      (weighted to the most recent month). There are several conditions that confound
      the HbA1c measurement such as hemolytic anaemia (lowers HbA1c) or aplastic
      anaemia (raises it), but in most circumstances HbA1c is a valid index of
      glycemia. The recommendation is to measure HbA1c every 3-6 months, and treat to a
      target level of < 7%. If these recommendations were successfully followed in most
      people with diabetes, long-term complications, especially microvascular
      complications, would be markedly reduced.

PMID- 15987017
TI  - Preoperative evaluation for non-cardiac surgery.
AB  - Internists are frequently consulted to perform preoperative risk assessments on
      patient undergoing non-cardiac surgery. Physicians need to assess the cardiac
      risk associated with the surgery, identify the patient's unique risk profile,
      recommend appropriate preoperative testing and make suitable recommendations. By
      a focused history-taking, physical examination, and application of current
      evidence-based guidelines in cardiac risk assessments, patients at high risk for
      complications at surgery can be identified and additional work-up suggested.
      Effective preoperative recommendation includes an assessment of risk (cardiac and
      non-cardiac), recommendations on medication adjustment, thrombo-embolic
      prophylaxis, and use of perioperative beta blockers. Prompt communication with
      the surgeon often enhances the quality of medical consultation and ensures
      compliance.

PMID- 15987018
TI  - Primary amyloidosis presenting with predominant lymphnodal masses.
AB  - A 50 year young farmer presented with clinical features of bilateral carpal
      tunnel syndrome and generalized lymphadenopathy including paratracheal and
      retroperitoneal lymphodes. The histological diagnosis confirmed primary
      amyloidosis of lymphnodes. Presentation of primary amyloidosis as lymphnodal mass
      with deposition of amyloid in carpal tunnel is extremely rare and can only be
      diagnosed by histochemistry. The clinical response to drugs is variable and needs
      surgical intervention for decompressive therapy which can improve the symptoms of
      carpal tunnel syndrome.

PMID- 15987019
TI  - Subcutaneous panniculitis-like T cell lymphoma in a HIV positive patient.
AB  - Immunocompromised patients are at increased risk for developing certain malignant
      tumors, particularly aggressive B cell lymphomas and extranodal lymphomas like
      primary central nervous system lymphoma and primary effusion lymphoma. T cell
      lymphomas are uncommon in these patients. We report a rare case of subcutaneous
      panniculitis-like T cell lymphoma in a HIV positive patient who presented with
      multiple subcutaneous nodules.

PMID- 15987020
TI  - Poisoning due to white seed variety of Abrus precatorius.
AB  - We report an unusual case of poisoning involving the white seed variety of Abrus
      precatorius that caused serious manifestations in a middle-aged male who had
      consumed the seeds on the advice of a folk medicine practitioner. He recovered
      after a prolonged duration of hospital treatment without any subsequent
      complications or sequelae. The case is being reported on account of its rarity.

PMID- 15987021
TI  - Calcium dobesilate-induced agranulocytosis.

PMID- 15987022
TI  - "Madras" motor neurone disease from "West Bengal".

PMID- 15987023
TI  - Medical philately (medical personalities on stamps). Dioscorides (CA 54-68 AD).

PMID- 15987024
TI  - [Understanding health and disease--from the patient's point of view, too].

PMID- 15987025
TI  - [Qualitative methods in medical research--conditions, possibilities and
      challenges].

PMID- 15987026
TI  - [Sleep-related respiration disorders. Definition, prevalence, pathophysiology and
      consequences].

PMID- 15987027
TI  - [Sleep-related respiration disorders. Diagnosis and treatment].

PMID- 15987028
TI  - [Narcolepsy in children--an overlooked diagnosis].

PMID- 15987029
TI  - [Bardet-Biedl syndrome. Insight into this rare inherited syndrome can lead to new
      knowledge of molecular mechanisms].

PMID- 15987030
TI  - [Adolescent social life and smoking in high schools--a dialectical perspective on
      health education].

PMID- 15987031
TI  - [Action research on own practice. Methodological challenges--secondary
      publication].

PMID- 15987032
TI  - [Patient demographics and evaluation of examinations in a neuromuscular clinic
      over a three-year period].

PMID- 15987033
TI  - [The influence of the referring physician's clinical evaluation on the waiting
      time guarantee for breast cancer in the county of Frederiksborg].

PMID- 15987034
TI  - [Narcolepsy in an 8-year-old boy].

PMID- 15987035
TI  - [Subclavian vein puncture].

PMID- 15987036
TI  - [Mycoplasma hominis meningitis in a premature baby with hydrocephalus].

PMID- 15987037
TI  - [Severe progress of septic shock with Mycobacterium tuberculosis infection].

PMID- 15987038
TI  - [Better results with a quick treatment of intestinal cancer--in symptomatic
      patients?].

PMID- 15987039
TI  - [Evidence-based rehabilitation in type 2 diabetes].

PMID- 15987040
TI  - [Medical concepts require content].

PMID- 15987041
TI  - [Probiotics in the treatment of infectious diarrhea].

PMID- 15987042
TI  - [Peripheral facial paralysis in adenocarcinoma of the middle ear].

PMID- 15987043
TI  - [Danish myoses].

PMID- 15987044
TI  - [Bacterial meningitis].

PMID- 15987045
TI  - [Lack of legal rights and pillory].

PMID- 15987047
TI  - [Chronic deep pain--a follow-up contribution I].

PMID- 15987046
TI  - [Health personnel against tobacco].

PMID- 15987048
TI  - [CT colonography instead of coloscopy. A new computer tomographic method in
      suspected colonic polyps or malignant tumors].

PMID- 15987049
TI  - [No evidence of positive effects of pacemaker use in paroxysmal atrial
      fibrillation].
AB  - Sixteen randomised controlled studies examining the use of pacemakers for the
      therapeutic prevention of atrial fibrillation were investigated. Four studies
      dealt with patients without conventional pacemaker indication. A minor positive
      effect was observed in one study. The validity of the observation is however
      limited due to a small number of patients and a short follow-up period. Five
      studies assessed the effect of overdrive pacing and different preventive pacing
      algorithms. A small, statistically significant positive effect was found in one
      of these studies. Six studies investigated dual site pacing or septal pacing.
      Five of these indicated a possible positive effect. Before this approach is
      implemented clinically, further studies are nevertheless required.

PMID- 15987050
TI  - [The use of antidepressive agents in psychotherapy is more and more common.
      Different views on combination therapy demand further studies].

PMID- 15987051
TI  - [Computerize drug handling! Scrutiny of drug prescriptions at four emergency
      hospitals show big shortages].
AB  - As part of quality assessment of hospital drug handling routines we conducted an
      audit of medical records in four major hospitals in order to investigate to what
      extent the prescriptions were correctly written, i.e. to what extent the name of
      the drug, dosage form, strength, administration route, dosage and dosage interval
      were given in the records. Only 20% of the prescriptions were given correctly.
      The failure rate was highest for route of administration and dosage intervals.
      According to a questionnaire, physicians, nurses and pharmacists were in favour
      of audits of this type recommended by the Swedish Medical Quality Council,
      believing that they will lead to improvement in the quality of the drug handling
      routines. Safe such routines are a leadership matter. It is also timely to
      implement computerised physician order entry systems. Such systems can form the
      basis for decision support, for example in dosage adjustments in relation to age
      and renal function, and the identification of drug interactions. This set-up
      would lead to improvement in the quality of health care provided in hospitals.

PMID- 15987052
TI  - [Norwegian pediatrician in Sweden...and Swedish pediatrician in Norway. After the
      dissolution of the union: completely different worlds, but still very much
      alike].

PMID- 15987054
TI  - [The OECD committee suggests international patient safety indicators].

PMID- 15987053
TI  - [Physician exchange in the Nordic countries was a limited phenomenon].

PMID- 15987056
TI  - [Non-therapeutic ventilation , organ transplantation and medical ethics].

PMID- 15987055
TI  - [LFN's evaluation of Inspra illustrates the need of drug committees!].

PMID- 15987057
TI  - [Intensive care after severe cerebral hemorrhage: improved survival--more organ
      donors!].

PMID- 15987058
TI  - [Dying in our time--an ethical no man's land?].

PMID- 15987059
TI  - [Less long-term numbness associated with laparoscopic hernia surgery].

PMID- 15987060
TI  - [Physicians employed by the insurance authorities in Vasternorrland have acted
      honourably].

PMID- 15987061
TI  - Letter from the guest editor. Magnetic resonance imaging of the abdomen--part I.

PMID- 15987062
TI  - Magnetic resonance imaging of the liver: review of techniques and approach to
      common diseases.
AB  - MR imaging examination of the liver should use a combination of single-shot T2W
      and breath-hold T1W images, and include gadolinium enhancement with acquisition
      of multiple phases. MR provides superior characterization of liver masses than
      CT, and multi-phase gadolinium enhancement including a properly timed arterial
      phase is critical. The T1 weighted pre-contrast images must include in-phase/out
      of-phase acquisitions, to assess hepatic lipid and or iron content, and
      dynamically enhanced post-gadolinium images. Timing of the arterial phase images
      is also critical for demonstration of acute hepatitis. The timing of the venous
      and equilibrium phase images are less critical, and are important for grading
      more severe acute hepatitis, demonstration of fibrosis, and for delineating
      vascular abnormalities. In cirrhosis, dynamic post-gadolinium images are critical
      for detection and characterization of regenerative or dysplastic nodules, and
      HCC. The same sequences useful for liver evaluation provide a comprehensive
      evaluation of all the soft tissues of the abdomen, and allow depiction of most of
      the important diseases, thus facilitating use of a universal protocol for
      abdominal imaging.

PMID- 15987063
TI  - Magnetic resonance imaging of the pancreas: the future is now.
AB  - MR imaging has made significant advances in recent years, with an increasingly
      important role in the detection, characterization, and staging of pancreatic
      diseases. MRI is appealing as a noninvasive imaging modality as it can evaluate
      the pancreas, the vasculature, and the pancreaticobiliary ducts in a single
      examination. Advantages of MRI include its excellent soft tissue contrast
      resolution and anatomic detail and absence of ionizing radiation. This article
      reviews the utility of MRI and its use not only as a problem-solving tool but its
      potential use as a primary examination (similar to CT) in a wide variety of
      pancreatic diseases.

PMID- 15987064
TI  - Magnetic resonance imaging of the kidney.
AB  - High tissue contrast, multiplanar image capabilities, and tissue characterization
      render MR into an ideal imaging modality for effective evaluation of a wide range
      of renal disorders. It provides high details of anatomy and can suggest the
      composition of lesions. Improvements of MRI technology during the last years have
      made MRI increasingly attractive for body imaging. Fast imaging sequences and
      parallel imaging techniques have proved to be useful in minimizing artifacts from
      respiratory motion and magnetic susceptibility differences providing superior
      imaging quality. Additionally, the use of renally eliminated paramagnetic
      contrast agents permits assessment of parenchymal perfusion and visualization of
      the excretion of the contrast medium providing information on renal function.

PMID- 15987065
TI  - Magnetic resonance imaging of the adrenal glands.
AB  - Differentiation of pathologic alterations of the adrenal glands is still a
      frequent and challenging problem of daily practice in radiology. Two main groups
      of patients have to be differentiated: those with clinical symptoms, mainly of
      endocrinopathies, and those in which a mass of the adrenal gland is detected
      incidentally. In the first group, magnetic resonance imaging (MRI) plays a minor
      role, although it allows to detect and often even differentiate the cause of the
      disease. In the second group, MRI has an excellent performance in differentiating
      between adenomas and non-adenomatous lesions of the adrenal glands.

PMID- 15987066
TI  - Magnetic resonance imaging in the characterization of pelvic masses.
AB  - Female pelvic masses most commonly arise from the reproductive tract, although
      masses may arise from other structures in the pelvis, such as the
      gastrointestinal or urinary tracts. The evaluation of a pelvic mass often begins
      with the physical exam and proceeds to ultrasound, computed tomography, or
      magnetic resonance imaging. Each of these modalities has a role in the work-up of
      pelvic masses and each modality has inherent advantages and disadvantages. The
      focus of this article is to demonstrate the imaging features and role of MRI, in
      contrast to CT, for detecting, characterizing, and staging pelvic masses. The
      differential diagnosis for pelvic masses is extremely broad. Clinical history,
      precise anatomical localization, and MR imaging characterization can
      significantly narrow the differential diagnosis. With recent advances in
      therapeutic strategies, a non-invasive, preoperative diagnosis is highly
      desirable to suggest prognosis and to tailor the treatment approach.

PMID- 15987067
TI  - [Pharmacogenetics--new therapeutic possibilities].

PMID- 15987068
TI  - [Classical pharmacogenetics].

PMID- 15987069
TI  - [Pharmacogenetic-assisted drug development. Regulatory aspects from the viewpoint
      of the Medical Products Agency].

PMID- 15987071
TI  - [The future of pharmacogenetics--cost-effectiveness and barriers].

PMID- 15987070
TI  - [Lifestyle medicine and pharmacogenetics--individualised drug therapy].

PMID- 15987072
TI  - [Drug targets: identification and evaluation].

PMID- 15987073
TI  - [Pharmacogenetic/regulatory aspects seen from the viewpoint of the industry].

PMID- 15987074
TI  - [Genomic classification of diseases].

PMID- 15987075
TI  - [How far are we from the clinical use of array technology?].

PMID- 15987076
TI  - [Toxicology and pharmacogenetics].

PMID- 15987077
TI  - [Genetic variations in the metabolism of environmental toxins].

PMID- 15987078
TI  - [Individual monitoring of thiopurine and methotrexate treatment].

PMID- 15987079
TI  - [Designer drugs and their rational use in clinical hematology].

PMID- 15987080
TI  - [Biomarkers: medical tradition and a brave new world].

PMID- 15987081
TI  - [Pharmacoepidemiology].

PMID- 15987082
TI  - [Status of and perspectives on psychiatric genomic medicine].

PMID- 15987083
TI  - [Psychopharmacology in a genomic perspective].

PMID- 15987084
TI  - [Future expectations when it comes to pharmacogenetics].

PMID- 15987085
TI  - [The Medical Products Agency and testosterone treatment. Act II].

PMID- 15987087
TI  - [ADHD?].

PMID- 15987086
TI  - [Antibiotics treatment at four intensive care units at a university hospital. A
      descriptive period-prevalence study].

PMID- 15987088
TI  - [Acupuncture can be a contribution in the treatment of postpartum depression].

PMID- 15987089
TI  - Microfluidic gradient-generating device for pharmacological profiling.
AB  - We describe an on-chip microfluidic gradient-generating device that generates
      concentration gradients spanning nearly 5 orders of magnitude starting from a
      single concentration. The exiting stream of drugs held at different
      concentrations remains laminar in a recording chamber and can be presented as 24
      discrete solutions to a cell-based sensor. The high-performance characteristics
      of the device are demonstrated by pharmacological screening of voltage-gated K+
      channels (hERG) and ligand-gated GABA(A) receptors using scanning-probe patch
      clamp measurements. Multiple data point dose-response curves and IC50 and EC50
      values were rapidly obtained, typically in less than 30 min, through its combined
      functionality of gradient generation and open-volume laminar flow. The device
      facilitates rapid pharmacological profiling of ion channel and GPCR effectors and
      enables the acquisition of large numbers of data points with minute sample
      consumption and handling.

PMID- 15987090
TI  - Long-range surface plasmon resonance imaging for bioaffinity sensors.
AB  - A novel bioaffinity sensor based on surface plasmon resonance (SPR) imaging
      measurements of a multiple-layered structure that supports the generation of long
      range surface plasmons (LRSPs) at the water-metal interface is reported. LRSPs
      possess longer surface propagation lengths, higher electric field strengths, and
      sharper angular resonance curves than conventional surface plasmons. LRSPR
      imaging is a version of SPR imaging that requires a symmetric dielectric
      arrangement around the gold thin film. This arrangement is created using an SF10
      prism/Cytop/gold/water multilayer film structure where Cytop is an amorphous
      fluoropolymer with a refractive index very close to that of water. LRSPR imaging
      experiments are performed at a fixed incident angle and lead to an enhanced
      response for the detection of surface binding interactions. As an example, the
      hybridization adsorption of a 16-mer single-stranded DNA (ssDNA) onto a two
      component ssDNA array was monitored with LRSPR imaging. The ssDNA array was
      created using a new fabrication technology appropriate for the LRSPR multilayers.

PMID- 15987091
TI  - Electrospray diagnostics by Fourier analysis of current oscillations and fast
      imaging.
AB  - The different spraying modes in electrospray ionization sources exhibit large
      variations in their ion yield and stability. To achieve consistently optimal ion
      production, active control of the spray parameters is desirable. To diagnose the
      changes in spraying mode, the spray current and its Fourier spectrum were
      monitored under a wide range of conditions, that is, as a function of the spray
      voltage, liquid flow rate, and composition. Most Fourier spectra indicated a
      strong dc component, a low-frequency branch at low flow rates and applied
      voltages, and a high-frequency branch and their harmonics. Changing of these
      parameters resulted in several spraying mode changes that were reflected in the
      Fourier spectra of the spray current. Significant mode changes and the
      malformation of the Taylor cone were detected as peak shifts or sudden changes in
      the spectrum quality. This was confirmed by fast imaging that showed a reduction
      in the size of the Taylor cone under hydrophobic tip conditions and rapid
      periodic ejection of filaments and droplets for high conductivity solutions.
      Comparing the oscillation frequencies of Taylor cones of different sizes, good
      correlation was found with the frequencies of capillary waves on comparablly
      sized liquid spheres. Spray stability was also linked with the positional
      stability of the contact line between the liquid meniscus and the capillary tip.

PMID- 15987092
TI  - From the mouse to the mass spectrometer: detection and differentiation of the
      endoproteinase activities of botulinum neurotoxins A-G by mass spectrometry.
AB  - We have developed an assay (Endopep-MS) that detects the specific endoproteinase
      activities of all seven BoNT types by mass spectrometry (MS). Each BoNT type
      cleaves a unique site on proteins involved in neuronal transmission. Target
      peptide substrates based on these proteins identify a BoNT type by its enzymatic
      action on the substrate and the production of two peptide products, which are
      then detected by matrix-assisted laser desorption/ionization time-of-flight MS or
      liquid chromatography electrospray ionization MS/MS. We showed the ability to
      detect all seven toxin types in a multiplexed assay format. The detection limits
      achieved range from 0.039 to 0.625 mouse LD(50)/mL for toxin types A, B, E, and F
      in a buffer system. The Endopep-MS assay is the first to differentiate all seven
      BoNT types, is sensitive, specific, and has the potential to quantify toxin
      activity.

PMID- 15987093
TI  - Potential of nuclear quadrupole resonance in pharmaceutical analysis.
AB  - Nuclear quadrupole resonance is a radio frequency (rf) spectroscopic technique,
      closely related to NMR, which can be used to detect signals from solids
      containing nuclei with spin quantum number >1/2. It is nondestructive, highly
      specific and noninvasive, requires no static magnetic field, and as such is
      currently used in the detection of explosives and narcotics. Recent technological
      advances in pulsed NQR methods have shortened detection times, eliminated
      spurious signals, and enhanced the sensitivity of detection of 14N frequencies,
      which lie in the low rf range of 0.4-6 MHz, encouraging a wider range of "real
      world" applications. This Perspective highlights some of the advantages of NQR,
      the applications in which it could be used, such as the quantification of
      pharmaceuticals and the identification of polymorphs. Other roles could include
      detection, analysis, and quality control of pharmaceuticals at all stages of
      manufacture. Finally, recent advances which enhance even further the sensitivity
      of detection will be discussed.

PMID- 15987094
TI  - Discovering known and unanticipated protein modifications using MS/MS database
      searching.
AB  - We present an MS/MS database search algorithm with the following novel features:
      (1) a novel protein database structure containing extensive preindexing and (2)
      zone modification searching, which enables the rapid discovery of protein
      modifications of known (i.e., user-specified) and unanticipated delta masses. All
      of these features are implemented in Interrogator, the search engine that runs
      behind the Pro ID, Pro ICAT, and Pro QUANT software products. Speed benchmarks
      demonstrate that our modification-tolerant database search algorithm is 100-fold
      faster than traditional database search algorithms when used for comprehensive
      searches for a broad variety of modification species. The ability to rapidly
      search for a large variety of known as well as unanticipated modifications allows
      a significantly greater percentage of MS/MS scans to be identified. We
      demonstrate this with an example in which, out of a total of 473 identified MS/MS
      scans, 315 of these scans correspond to unmodified peptides, while 158 scans
      correspond to a wide variety of modified peptides. In addition, we provide
      specific examples where the ability to search for unanticipated modifications
      allows the scientist to discover: unexpected modifications that have biological
      significance; amino acid mutations; salt-adducted peptides in a sample that has
      nominally been desalted; peptides arising from nontryptic cleavage in a sample
      that has nominally been digested using trypsin; other unintended consequences of
      sample handling procedures.

PMID- 15987095
TI  - Development of ultrahigh-throughput NMR spectroscopic analysis utilizing
      capillary flow NMR technology.
AB  - An ultrahigh-throughput method for acquiring 1H NMR spectra is described. By
      constructing a continuous flow system utilizing an HPLC pump, autosampler, and a
      capillary flow NMR probe, it was possible to inject samples into the NMR
      spectrometer every 30 s using a continuous flow rate of 30 microL/min. 1H NMR
      spectroscopic data were acquired continuously into a pseudo-2D data file, with a
      96-well-plate completed in <50 min. Spectra in continuous flow mode were readily
      obtained from approximately 3.4 mug (500 MHz), while the LOD was <850 ng. There
      was found to be little variation in either sample broadening within the flow
      system or signal intensities between multiple injections. This system offers
      several advantages over more conventional NMR spectroscopic analyses, notably the
      limited solvent required, high sensitivity, high speed, and improved spectral
      quality as a result of reduced spectral "dead" regions resulting from residual
      solvent levels.

PMID- 15987096
TI  - Arrayed time-of-flight mass spectrometry for time-critical detection of hazardous
      agents.
AB  - The design and operation of an arrayed time-of-flight (TOF) mass spectrometer for
      simultaneous data acquisition from multiple samples is described. Versions of the
      instrument employ sets of two or four linear or reflectron mass analyzers. They
      are housed in the same vacuum chamber and utilize the same laser for ion
      desorption. Instrument performance is illustrated in the example of a two-linear
      mass-analyzer array using MALDI-MS for mixtures of commercially available
      proteins as well as intact microorganisms. We also describe the properties of a
      novel short delay time (<170 ns) pulsed extraction method for linear TOF
      analyzers. This configuration allows uniform resolution improvements to be
      achieved in a wide m/z range. In addition, we present multiplexed sample
      preparation methods, using different reagents prior to mass analysis in the
      arrayed system, to increase the overall sensitivity of the MS method and to allow
      wider and more efficient detection across the entire range of potentially
      hazardous agents. In addition to the multifold increase in data collection rates,
      arrayed TOF-MS configurations provide a high degree of redundancy, critical for
      rapid, high confidence agent identification as well as for reduction in false
      alarm rates.

PMID- 15987097
TI  - Electrochemical sensing based on redox mediation at carbon nanotubes.
AB  - An electrochemical sensing platform was developed based on the integration of
      redox mediators and carbon nanotubes (CNT) in a polymeric matrix. To demonstrate
      the concept, a redox mediator Azure dye (AZU) was covalently attached to
      polysaccharide chains of chitosan (CHIT) and interspersed with CNT to form
      composite films for the amperometric determination of beta-nicotinamide adenine
      dinucleotide (NADH). The incorporation of CNT into CHIT-AZU matrix facilitated
      the AZU-mediated electrooxidation of NADH. In particular, CNT decreased the
      overpotential for the mediated process by an extra 0.30 V and amplified the NADH
      current by approximately 35 times (at -0.10 V) while reducing the response time
      from approximately 70 s for CHIT-AZU to approximately 5 s for CHIT-AZU/CNT films.
      These effects were discussed in terms of the AZU/CNT synergy, which improved
      charge propagation through the CHIT-AZU/CNT matrix. The concept of CNT
      facilitated redox mediation in polymeric matrixes has a potential to be of
      general interest for expediting redox processes in electrochemical devices such
      as sensors, biosensors, and biological fuel cells and reactors.

PMID- 15987098
TI  - Monolithic capillary-based ion-selective electrodes.
AB  - Poly(styrene-co-divinylbenzene)-based monolithic capillaries of an inner diameter
      of 200 mum and a length of 2-5 mm have been used to construct Ca2+-, Ag+-, and
      Na+-selective electrodes. The membranes consist of a solution of ionophore and
      ion exchanger in bis(2-ethylhexyl) sebacate or 2-nitrophenyl octyl ether, which
      are used as plasticizers in conventional PVC-based membranes. With capillaries of
      low porosity, the potentiometric responses down to 10(-8)-10(-9) M solutions do
      not depend on the composition of the internal solution, which indicates a strong
      suppression of transmembrane ion fluxes. Thus, no tedious optimization of the
      inner solution is required with monolith ISEs. The lower detection limits of Ag+-
      and Ca2+-ISEs are comparable to the best ones obtained earlier with optimized
      inner solutions. Additionally, a monolithic Na+-selective ISE has been obtained
      exhibiting a lower detection limit of 3 x 10(-8) M Na+. With monolithic
      capillaries of higher porosity and fused-silica GC capillaries, the transmembrane
      flux effects are noticeable but still significantly smaller than with
      conventional PVC membranes.

PMID- 15987099
TI  - Stable permanently hydrophilic protein-resistant thin-film coatings on
      poly(dimethylsiloxane) substrates by electrostatic self-assembly and chemical
      cross-linking.
AB  - Poly(dimethylsiloxane) (PDMS) is a biomaterial that presents serious surface
      instability characterized by hydrophobicity recovery. Permanently hydrophilic
      PDMS surfaces were created using electrostatic self-assembly of polyethyleneimine
      and poly(acrylic acid) on top of a hydrolyzed poly(styrene-alt-maleic anhydride)
      base layer adsorbed on PDMS. Cross-linking of the polyelectrolyte multilayers
      (PEMS) by carbodiimide coupling and covalent attachment of poly(ethylene glycol)
      (PEG) chains to the PEMS produced stable, hydrophilic, protein-resistant
      coatings, which resisted hydrophobicity recovery in air. Attenuated total
      reflection Fourier transform infrared spectroscopy and X-ray photoelectron
      spectroscopy revealed that the thin films had excellent chemical stability and
      resisted hydrophobicity recovery in air over 77 days of measurement. The spectra
      also showed a dense coverage for PEG dialdehyde and excellent resistance to
      protein adsorption from undiluted rat serum. Atomic force microscopy revealed
      dense coverage with PEG dialdehyde and PEG diamine. Contact angle measurements
      showed that all films were hydrophilic and that the PEG dialdehyde-topped thin
      film had a virtually constant contact angle (approximately 20 degrees ) over the
      five months of the study. Electrokinetic analysis of the coatings in
      microchannels always exposed to air also gave good protein separation and
      constant electroosmotic flow during the five months that the measurements were
      done. We expect that the stable, hydrophilic, protein-resistant thin-film
      coatings will be useful for many applications that require long-term surface
      stability.

PMID- 15987100
TI  - Detection and quantification of on-chip phosphorylated peptides by surface
      plasmon resonance imaging techniques using a phosphate capture molecule.
AB  - We describe herein a detection and quantification system for on-chip
      phosphorylation of peptides by surface plasmon resonance (SPR) imaging techniques
      using a newly synthesized phosphate capture molecule (i.e., biotinylated zinc(II)
      complex). The biotinylated compound is a dinuclear zinc(II) complex that is
      suitable for accessing phosphate anions as a bridging ligand on the two zinc(II)
      ions. The compound was exposed on the peptide array and detected with
      streptavidin (SA) via a biotin-SA interaction by SPR imaging. In the conventional
      method using antibody, both anti-phosphoserine and anti-phosphotyrosine
      antibodies were required for phosphoserine and phosphotyrosine detection,
      respectively. Detection of the phosphate group by the zinc(II) complex, however,
      was independent of the phosphorylated amino acid residues. The calibration curve
      for the phosphorylation ratios was established with a calibration chip, on which
      phosphoserine-containing peptide probes were immobilized. The peptide probes,
      which were phosphorylated on the surface by protein kinase A, were detected and
      quantified by SPR imaging using the zinc(II) complex, SA, and anti-SA antibody.
      The reaction rate and the kinetics of on-chip phosphorylation were also evaluated
      with the peptide array. The phosphorylation ratio was saturated at approximately
      20% in 2 h in this study.

PMID- 15987101
TI  - Experimental validation of the tetrahedral skeleton model pressure drop
      correlation for silica monoliths and the influence of column heterogeneity.
AB  - This paper describes the use of computational fluid dynamics for the calculation
      of the flow resistance through computer-generated models resembling silica
      monoliths. This study was undertaken to determine the effect of skeleton
      heterogeneity on the flow resistance and, more precisely, to test the hypothesis
      that increased skeleton heterogeneity decreases the flow resistance. To evaluate
      the proposed model, 24 real silica monoliths have been prepared using the same
      method, covering a wide range of skeleton sizes (2.2 microm < d(s) < 8 microm)
      and porosities (0.47 < epsilon < 0.66). The permeability of these monoliths was
      determined by pressure drop measurements, and structural information was obtained
      by image analysis of laser scanning confocal microscopy-generated 3D images of
      the skeleton structure. The results indicate that the presence of preferential
      flow paths due to an increased heterogeneity of the flow through pore space
      reduces the flow resistance of monolithic media. It is also shown that the pore
      size is hence a much better suited scaling dimension than the skeleton size to
      reduce the permeability of monolithic columns.

PMID- 15987102
TI  - Computer-controlled microcirculatory support system for endothelial cell culture
      and shearing.
AB  - Endothelial cells (ECs) lining the inner lumen of blood vessels are continuously
      subjected to hemodynamic shear stress, which is known to modify EC morphology and
      biological activity. This paper describes a self-contained microcirculatory EC
      culture system that efficiently studies such effects of shear stress on EC
      alignment and elongation in vitro. The culture system is composed of elastomeric
      microfluidic cell shearing chambers interfaced with computer-controlled movement
      of piezoelectric pins on a refreshable Braille display. The flow rate is varied
      by design of channels that allow for movement of different volumes of fluid per
      variable-speed pump stroke. The integrated microfluidic valving and pumping
      system allowed primary EC seeding and differential shearing in multiple
      compartments to be performed on a single chip. The microfluidic flows caused ECs
      to align and elongate significantly in the direction of flow according to their
      exposed levels of shear stress. This microfluidic system overcomes the small flow
      rates and the inefficiencies of previously described microfluidic and macroscopic
      systems respectively to conveniently perform parallel studies of EC response to
      shear stress.

PMID- 15987103
TI  - Electrokinetically based approach for single-nucleotide polymorphism
      discrimination using a microfluidic device.
AB  - In this work, we describe and implement an electrokinetic approach for single
      nucleotide polymorphism (SNP) discrimination using a PDMS/glass-based
      microfluidic chip. The technique takes advantage of precise control of the
      coupled thermal (Joule heating), shear (electroosmosis), and electrical
      (electrophoresis) energies present at an array of probes afforded by the
      application of external electrical potentials. Temperature controllers and
      embedded thermal devices are not required. The chips can be easily and
      inexpensively fabricated using standard microarray printing methods combined with
      soft-lithography patterned PDMS fluidics, making these systems easily adaptable
      to applications using higher density arrays. Extensive numerical simulations of
      the coupled flow and thermal properties and microscale thermometry experiments
      are described and used to characterize the in-channel conditions. It was found
      that optimal conditions for SNP detection occur at a lower temperature on-chip
      than for typical microarray experiments, thereby revealing the importance of the
      electrical and shear forces to the overall process. To demonstrate the clinical
      utility of the technique, the detection of single-base pair mutations in the
      survival motor neuron gene, associated with the childhood disease spinal muscular
      atrophy, is conducted.

PMID- 15987104
TI  - NMR-based biosensing with optimized delivery of polarized 129Xe to solutions.
AB  - Laser-enhanced (LE) 129Xe nuclear magnetic resonance (NMR) is an exceptional tool
      for sensing extremely small physical and chemical changes; however, the difficult
      mechanics of bringing polarized xenon and samples of interest together have
      limited applications, particularly to biological molecules. Here we present a
      method for accomplishing solution 129Xe biosensing based on flow (bubbling) of LE
      129Xe gas through a solution in situ in the NMR probe, with pauses for data
      acquisition. This overcomes fundamental limitations of conventional solution
      state LE 129Xe NMR, e.g., the difficulty in transferring hydrophobic xenon into
      aqueous environments, and the need to handle the sample to refresh LE 129Xe after
      an observation pulse depletes polarization. With this new method, we gained a
      factor of >100 in sensitivity due to improved xenon transfer to the solution and
      the ability to signal average by renewing the polarized xenon. Polarized xenon in
      biosensors was detected at very low concentrations, </=250 nanomolar, while
      retaining all the usual information from NMR. This approach can be used to
      simultaneously detect multiple sensors with different chemical shifts and is also
      capable of detecting signals from opaque, heterogeneous samples, which is a
      unique advantage over optical methods. This general approach is adaptable for
      sensing minute quantities of xenon in heterogeneous in vitro samples, in
      miniaturized devices and should be applicable to certain in-vivo environments.

PMID- 15987105
TI  - Glucose sensing using near-infrared surface-enhanced Raman spectroscopy: gold
      surfaces, 10-day stability, and improved accuracy.
AB  - This research presents the achievement of significant milestones toward the
      development of a minimally invasive, continuously monitoring, glucose-sensing
      platform based on the optical quantitation of glucose in interstitial fluid. We
      expand our initial successes in the measurement of glucose by surface-enhanced
      Raman scattering (SERS), demonstrating substantial improvements not only in the
      quality and optical properties of the substrate system itself but also in the
      robustness of the measurement methodology and the amenability of the technique to
      compact, diode laser-based instrumentation. Herein, we compare the long-term
      stability of gold to silver film over nanosphere (AuFON, AgFON) substrates
      functionalized with a partitioning self-assembled monolayer (SAM) using both
      electrochemical and SERS measurements. AuFONs were found to be stable for a
      period of at least 11 days. The switch to AuFONs not only provides a more stable
      surface for SAM formation but also yields better chemometric results, with
      improved calibration and validation over a range of 0.5-44 mM (10-800 mg/dL).
      Measured values for glucose concentrations in phosphate-buffered saline (pH
      approximately 7.4) based on 160 independent SERS measurements on AuFONs have a
      root-mean-square error of prediction of 2.7 mM (49.5 mg/dL), with 91% of the
      values falling within an extended A-B range on an expanded Clarke error grid.
      Furthermore, AuFONs exhibit surface plasmon resonances at longer wavelengths than
      similar AgFONs, which make them more efficient for SERS at near-infrared
      wavelengths, enabling the use of low-power diode lasers in future devices.

PMID- 15987106
TI  - Analysis of polyethylene by using cyclopentadienyl cobalt chemical ionization
      combined with laser-induced acoustic desorption/fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - A new mass spectrometric method has been developed for the analysis of low
      molecular weight polyethylene (PE). Laser-induced acoustic desorption (LIAD),
      combined with chemical ionization by the cyclopentadienyl cobalt radical cation
      (CpCo.+) in a Fourier transform ion cyclotron resonance mass spectrometer,
      produces predominantly a quasimolecular ion, (R + CpCo - 2H2).+, for each PE
      oligomer (R). An examination of artificial alkane mixtures revealed no mass bias
      for alkanes of differing molecular weights. However, the success of the
      LIAD/CpCo.+ CI technique depends greatly upon the LIAD sample preparation method
      used. Several sample preparation methods were evaluated, and pneumatically
      assisted spin coating was concluded to provide the best mass spectra as a result
      of its ability to provide uniform PE coverage on the LIAD foils. The molecular
      weight distributions measured for several low molecular weight PE samples (200
      655) were found to be in good agreement with manufacturers' values as determined
      by gel permeation chromatography.

PMID- 15987107
TI  - Determination of bromine stable isotopes using continuous-flow isotope ratio mass
      spectrometry.
AB  - A new methodology for bromine stable isotope determination by continuous-flow
      isotope ratio mass spectrometry (CF-IRMS) was developed. The technique was tested
      on inorganic samples. Inorganic bromide was precipitated in the form of silver
      bromide by using silver nitrate in a standard methodology. Bromine stable isotope
      analysis was carried out on methyl bromide (CH3Br) after converting silver
      bromide to methyl bromide by reacting it with methyl iodide (CH3I). The system
      used in this study is an IsoPrime IRMS, with analytical capabilities of both dual
      inlet and continuous-flow modes coupled with an Agilent 6890 GC equipped with a
      CTC Analytics CombiPAL autosampler. This new technique measures samples as small
      as 0.2 mg of AgBr (1 micromol of Br-). The bromine stable isotope analysis using
      continuous flow technology showed excellent precision and accuracy. The internal
      precision using pure methyl bromide gas is better than +/-0.03 per thousand (+/
      SD); the external precision using seawater standard is better than +/-0.06 per
      thousand (+/-SD) for n = 12. Moreover, the sample analysis time is 16 min, as
      compared to 75 min needed in previous techniques. This allows for 50 samples to
      be analyzed in 1 day, as compared to 8 samples using the conventional techniques.
      A series of natural saline formation waters and brines from sedimentary and
      crystalline rock environments was measured by this new methodology to test the
      potential natural range of delta81Br. The bromine isotopic composition of the
      samples ranged from 0.00 to +1.80 per thousand relative to standard mean ocean
      bromide (SMOB). Initial trends and distinctive isotopic difference were noticed
      between crystalline shield brines and sedimentary formation brines.

PMID- 15987108
TI  - Potential for using isotopically altered metalloproteins in species-specific
      isotope dilution analysis of proteins by HPLC coupled to inductively coupled
      plasma mass spectrometry.
AB  - The production and evaluation of an isotopically enriched metalloprotein standard
      for use as a calibrant in species-specific isotope dilution analysis by HPLC
      coupled to inductively coupled plasma mass spectrometry is described. Using a
      model system involving the copper-containing protein rusticyanin (Rc) from the
      bacterium Acido-thiobacillus ferrooxidans, it was possible to demonstrate the
      analytical conditions that could be used for the measurement of metalloproteins
      by on-line IDMS analysis. Rc was chosen because it is a well-characterized
      protein with an established amino acid sequence and can be produced in suitable
      quantities using a bacterial recombinant system. Three different forms of the
      protein were studied by organic and inorganic mass spectrometry: the native form
      of the protein containing a natural isotopic profile for copper, an isotopically
      enriched species containing virtually all of its copper as the 65Cu isotope, and
      the nonmetalated apo form. Incorporation of the copper isotopes into the apo form
      of the protein was determined using a UV-vis spectrophotometric assay and shown
      to be complete for each of the copper-containing species. The experimental
      conditions required to maintain the conformational form of the protein with a
      nonexchangeable copper center were established using +ve electrospray mass
      spectrometry. A pH 7.0 buffer was found to afford the most appropriate
      conditions, and this was then used with HPLC-ICP-MS to verify the stability of
      the copper center by analysis of mixtures of different isotopic solutions. No
      exchange of the enriched copper isotope from Rc with an added naturally abundant
      inorganic copper cation was observed under a neutral pH environment, indicating
      that species-specific ID-MS analysis of metalloproteins is possible.

PMID- 15987109
TI  - MALDI of individual biomolecule-containing airborne particles in an ion trap mass
      spectrometer.
AB  - Individual airborne biomolecule-containing particles were detected and
      characterized in near real-time by matrix-assisted laser desorption/ionization
      (MALDI) with an ion trap mass spectrometer. Biomolecule-containing particles were
      laboratory-generated and passed through a heated region containing a solution of
      matrix in equilibrium with the gas phase. Passage into a cooler region created a
      supersaturation, resulting in rapid deposition of the matrix vapor onto the
      biomolecule-containing particles, whereupon they were sampled into the inlet of
      our spectrometer. The coated particles were collimated and individually sized by
      light-scattering-based time-of-flight. When the sized particle reached the center
      of the ion trap, it was irradiated with a focused 266-nm laser, and the resulting
      ions were mass-analyzed. Mass spectra of leucine enkephalin, bradykinin,
      substance P, and polylysine-containing particles were determined with attomole
      sensitivity. Structural information of the peptides contained in an individual
      particle was obtained by tandem mass spectrometry. Analysis of the results yields
      insights into the aerosol laser ablation ionization process that suggests an
      optically limited mechanism for ion production that has interesting ramifications
      on the utility of aerosol-based MALDI as an analytical technique.

PMID- 15987110
TI  - Intelligent signal processing for detection system optimization.
AB  - A wavelet-neural network signal processing method has demonstrated approximately
      10-fold improvement over traditional signal processing methods for the detection
      limit of various nitrogen and phosphorus compounds from the output of a
      thermionic detector attached to a gas chromatograph. A blind test was conducted
      to validate the lower detection limit. All 14 of the compound spikes were
      detected when above the estimated threshold, including all 3 within a factor of 2
      above the threshold. In addition, two of six spikes were detected at levels of
      half the concentration of the nominal threshold. Another two of the six would
      have been detected correctly if we had allowed human intervention to examine the
      processed data. One apparent false positive in five nulls was traced to a solvent
      impurity, whose presence was subsequently identified by analyzing a solvent
      aliquot evaporated to 1% residual volume, while the other four nulls were
      properly classified. We view this signal processing method as broadly applicable
      in analytical chemistry, and we advocate that advanced signal processing methods
      should be applied as directly as possible to the raw detector output so that less
      discriminating preprocessing and postprocessing does not throw away valuable
      signal.

PMID- 15987111
TI  - Geometry-independent plate height representation methods for the direct
      comparison of the kinetic performance of LC supports with a different size or
      morphology.
AB  - The advantages of representing experimental plate height data as a plot of
      Kv/u0(2) or H2/Kv versus Kv/(Hu0) instead of as H versus u0 are discussed
      (Kv=column permeability). Multiplying the values on both axes by the ratio of a
      reference pressure drop and mobile-phase viscosity, the obtained plots directly
      yield the kinetic performance limits of the tested support structure, without any
      need for further numerical optimization. Directly showing the range of plate
      numbers or analysis times wherein the tested support geometry can yield faster
      separations or produce more plates than another support type, such kinetic plots
      are ideally suited to compare the performance of differently shaped or sized LC
      supports. The approach hence obviates the need for a common reference length,
      which is a clear problem if it is attempted to compare differently shaped
      supports on the basis of their flow resistance phi and reduced plate height h. It
      is also shown how an MS Excel template file, only requiring the user to paste the
      column permeability Kv and a series of experimental (u0, H) data, can be used to
      automatically establish a series of so-called kinetic performance (KP) numbers,
      which can be used to completely describe the performance characteristics of the
      considered support. The advantages of the proposed data representation methods
      are demonstrated by applying them to several recent literature plate height data
      sets, showing that the obtained kinetic plots directly visualize the range of
      plate numbers where new approaches such as ultra-high-pressure HPLC or the use of
      open-porous silica monoliths can be expected to provide a substantial gain and
      where not. The data analysis also showed that the most generally relevant KP
      numbers are N(opt) (the plate number for which the support achieves its best
      analysis time/pressure cost ratio), t(opt) (the time needed to obtain N(opt)
      plates), and t(1K) (the time needed to generate 1000 or 1 kilo of theoretical
      plates). These KP numbers are much more informative than the H(min), u(0,opt),
      and Kv data traditionally employed to quantify the performance of LC supports.

PMID- 15987112
TI  - Nonmolecular solvents in separation methods: dual nature of room temperature
      ionic liquids.
AB  - Room temperature ionic liquids (RTIL) are molten salts starting to be used as
      nonmolecular solvents in separation methods mainly for their extremely low vapor
      pressure and thermal stability. RTILs are formed by an anion associated to a
      cation. This intrinsic structure gives them a dual nature. When used as additives
      in RPLC mobile phases to enhance basic compound separation, RTILs lose their
      particular physicochemical properties to become just salts. However, a given RTIL
      is not equivalent to another one made with the same cation. It is shown that both
      the anion and the cation contribute to solute retention and peak efficiency
      extending beyond simple "salting-out" or ion-pairing effects. Nine different
      alkyl-methyl-imidazolium ionic liquids with different alkyl chain length and
      chloride or BF(4-) or PF(6-) anions were used as additives (50 mM max. conc.) in
      the liquid chromatography separation of some cationic basic solutes on a Kromasil
      C18 column. It is shown with sodium salts and an acetonitrile-water 30/70 v/v
      mobile phase that anions can adsorb on the stationary phase surface according to
      their lyotropic character. They can also form ion pairs with the cationic basic
      solutes. Alkyl-imidazolium cations also adsorb on the C18 bonded stationary phase
      due to hydrophobic character depending on their alkyl chain length. Anion
      adsorption dramatically increases the cationic solute retention factors when
      cation adsorption decreases them. The cation adsorption is mainly responsible for
      peak shape and efficiency enhancements. RTILs are additives that enhance the
      basic cationic solute peak shape changing peak position. A wise choice of the
      appropriate combination of anion lyotropy with imidazolium cation hydrophobicity
      allows playing with solute selectivity and analysis duration.

PMID- 15987113
TI  - Combining lectin microcolumns with high-resolution separation techniques for
      enrichment of glycoproteins and glycopeptides.
AB  - Silica-based lectin microcolumns are described in this study together with the
      chemical procedures necessary for their preparation. The analytical merits of
      Canavalia ensiformis and Sambucus nigra lectins, [immobilized on activated
      macroporous silica], such as binding capacity, trapping reproducibility, and
      substrate selectivity, have been evaluated using model glycoproteins. The
      described microcolumns are applicable to high-pressure analytical schemes
      utilizing microvalving procedures, washing steps, and quantitative desorption for
      LC/MS analysis. The described analytical systems are amenable to the applications
      aiming at fractionation of complex glycopeptide mixtures and determination of the
      sites of glycosylation.

PMID- 15987114
TI  - An enzyme immunoanalytical system based on sequential cross-flow chromatography.
AB  - A new enzyme immunoanalytical concept that can be used for point-of-care testing
      has been investigated. Enzyme as a tracer requires a separate reaction step for
      signal generation, which follows the completion of immune complex formation with
      analyte (e.g., Hepatitis B surface antigen) in a sample. This has been a major
      factor limiting its utilization within the laboratory. We carried out such
      sequential processes employing chromatographic analysis, using two crosswise
      arranged membrane pads in vertical and horizontal directions. The vertically
      arranged pads were the same as those in the usual format for pregnancy testing,
      for instance, with the exception of the use of horseradish peroxidase (HRP) as
      tracer. By placing the horizontally arranged pads on each lateral side of the
      signal generation pad in the vertical arrangement, they were employed to supply
      substrate to the enzyme present in the immune complexes. The substrate flow was
      initiated after the antigen-antibody bindings to produce a signal, which was
      typically a color change in proportion to the analyte concentration. Under
      optimal conditions, the use of HRP labeling increased the detection capability of
      the assay approximately 30 times compared to that of gold colloids. Potential
      advantages of using the concept investigated are (1) provision of a rapid and
      simple immunoassay, (2) satisfaction of a clinical need for highly sensitive
      determination of analyte, and (3) utilization of relatively inexpensive, portable
      quantitation means.

PMID- 15987115
TI  - Analysis of gangliosides directly from thin-layer chromatography plates by
      infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight
      mass spectrometry with a glycerol matrix.
AB  - A novel method is presented for direct coupling of high-performance thin-layer
      chromatography (HPTLC) with matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) for the analysis of biomolecules. A first key feature is
      the use of a liquid matrix (glycerol), which provides a homogeneous wetting of
      the silica gel and a simple and fast MALDI preparation protocol. A second is the
      use of an Er:YAG infrared laser, which ablates layers of approximately 10-microm
      thickness of analyte-loaded silica gel and provides a soft desorption/ionization
      of even very labile analyte molecules. The orthogonal time-of-flight mass
      spectrometer employed in this study, finally provides a high accuracy of the mass
      determination, which is independent of any irregularity of the silica gel
      surface. The analytical potential of the method is demonstrated by the
      compositional mapping of a native GM3 (II(3)-alpha-Neu5Ac-LacCer) ganglioside
      mixture from cultured Chinese hamster ovary cells. The analysis is characterized
      by a high relative sensitivity, allowing the simultaneous detection of various
      major and minor GM3 species directly from individual HPTLC analyte bands. The
      lateral resolution of the direct HPTLC-MALDI-MS analysis is defined by the laser
      focus diameter of currently approximately 200 microm. This allows one to
      determine mobility profiles of individual species with a higher resolution than
      by reading off the chromatogram by optical absorption. The fluorescent dye
      primuline was, furthermore, successfully tested as a nondestructive, MALDI
      compatible staining agent.

PMID- 15987116
TI  - Plasma phospholipid metabolic profiling and biomarkers of type 2 diabetes
      mellitus based on high-performance liquid chromatography/electrospray mass
      spectrometry and multivariate statistical analysis.
AB  - Liquid chromatography/mass spectrometry (LC/MS) followed by multivariate
      statistical analysis has been successfully applied to the plasma phospholipids
      metabolic profiling in type 2 diabetes mellitus (DM-2). Principal components
      analysis and partial least-squares discriminant analysis (PLS-DA) models were
      tested and compared in class separation between the DM2 and control. The
      application of an orthogonal signal correction filtered model highly improved the
      class distinction and predictive power of PLS-DA models. Additionally, unit
      variance scaling was also tested. With this methodology, it was possible not only
      to differentiate the DM2 from the control but also to discover and identify the
      potential biomarkers with LC/MS/MS. The proposed method shows that LC/MS
      combining with multivariate statistical analysis is a complement or an
      alternative to NMR for metabonomics applications.

PMID- 15987117
TI  - Unambiguous identification of volatile organic compounds by proton-transfer
      reaction mass spectrometry coupled with GC/MS.
AB  - Interest in on-line measurements of volatile organic compounds (VOCs) is
      increasing, as sensitive, compact, and affordable direct inlet mass spectrometers
      are becoming available. Proton-transfer reaction mass spectrometry (PTR-MS)
      distinguishes itself by its high sensitivity (low ppt range), high time
      resolution (200 ms), little ionization-induced fragmentation, and ionization
      efficiency independent of the compound to be analyzed. Yet, PTR-MS has a
      shortcoming. It is a one-dimensional technique that characterizes compounds only
      via their mass, which is not sufficient for positive identification. Here, we
      introduce a technical and analytical extension of PTR-MS, which removes this
      shortcoming, while preserving its salient and unique features. Combining
      separation of VOCs by gas chromatography (GC) with simultaneous and parallel
      detection of the GC effluent by PTR-MS and electron impact MS, an unambiguous
      interpretation of complex PTR-MS spectra becomes feasible. This novel development
      is discussed on the basis of characteristic performance parameters, such as
      resolution, linear range, and detection limit. The recently developed drift tube
      with a reduced reaction volume is crucial to exploit the full potential of the
      setup. We illustrate the performance of the novel setup by analyzing a complex
      food system.

PMID- 15987118
TI  - On-line liquid chromatography electrospray ionization mass spectrometry for the
      characterization of kappa- and iota-carrageenans. Application to the hybrid iota
      /nu-carrageenans.
AB  - An on-line liquid chromatography electrospray ionization mass spectrometry (MS)
      method was developed for the characterization of polymers of kappa- (extracted
      from Kappaphycus alvarezii), iota-, and hybrid iota-/nu-carrageenans (both
      extracted from Eucheuma denticulatum) enzymatically digested with specific
      carrageenase enzymes. Applying either CID MS/MS or in-source fragmentation
      mechanisms, the results demonstrated that none of the polymers of kappa- or iota
      carrageenans existed with their ideal repeating units. On the polymer of kappa
      carrageenan, the nonideal structures identified consisted of iota-neocarrabiose
      sulfate units. On the polymer of iota-carrageenan, the nonideal structures
      identified consisted of the following: (i) kappa-neocarrabiose sulfate units,
      (ii) iota-neocarrabiose sulfate units with an additional sulfate group, and (iii)
      iota-neocarrabiose sulfate units with an additional sulfate and a pyruvate acetal
      group. For both kappa- and iota-carrageenans, the nonideal structures were
      randomly distributed on the polymers. The method was then applied for the
      characterization of a hybrid polymer of iota-/nu-carrageenans, enzymatically
      digested with iota-carrageenase. The results did not reveal an ideal
      oligosaccharide of nu-carrageenan, suggesting that the iota-carrageenase enzyme
      could cleave only reduced "densities" of nu-carrageenan repeating units. In
      addition, information about the sequence of hybrid iota-/nu-carrageenans from E.
      denticulatum is deduced.

PMID- 15987119
TI  - Quantitative chemical derivatization technique in time-of-flight secondary ion
      mass spectrometry for surface amine groups on plasma-polymerized ethylenediamine
      film.
AB  - A chemical derivatization technique in time-of-flight secondary ion mass
      spectrometry (TOF-SIMS) has been developed to quantify the surface density of
      amine groups of plasma-polymerized ethylenediamine thin film deposited on a glass
      surface by inductively coupled plasma chemical vapor deposition. Chemical tags of
      4-nitrobenzaldehyde or pentafluorobenzaldehyde were hybridized with the surface
      amine groups and were detected in TOF-SIMS spectra as characteristic molecular
      secondary ions. The surface amine density was controlled in a reproducible manner
      as a function of deposition plasma power and was also quantified using UV-visible
      spectroscopy. A good linear correlation was observed between the results of TOF
      SIMS and UV-visible measurements as a function of plasma power. This shows that
      the chemical derivatization technique in TOF-SIMS analysis would be useful in
      quantifying the surface density of specific functional groups that exist on the
      organic surface.

PMID- 15987120
TI  - Electron transfer reactions of glucose oxidase at Au111 electrodes modified with
      phenothiazine derivatives.
AB  - The catalytic reaction of glucose oxidase (GOx) mediated by 3-(10
      phenothiazyl)propionic acid (PT-PA) and phenothiazine-labeled poly(ethylene
      oxide) (PT-PEO1000) that are covalently bonded to Au(111) electrodes has been
      investigated. The PT-PA and PT-PEO1000 are reacted with 2-aminoethanethiol (AET),
      followed by the formation of a self-assembled monolayer (SAM) onto the Au
      surface. The PT group immobilized on the SAM of AET acts as an effective mediator
      for the electron transfer (ET) between the electrode and the FAD center of freely
      diffusing GOx in solution. The ET rate constant estimated from the catalytic
      current using a newly derived equation is larger by 1 order of magnitude for the
      PT-PA-modified system (1.1 x 10(5) dm(3) mol(-1) s(-1)) than for the PT-PEO1000
      system (1.4 x 10(4) dm(3) mol(-1) s(-1)). The order of the magnitude of the ET
      rate constant clearly contrasts with the GOx hybrid systems that we previously
      investigated (Anal. Chem. 2003, 75, 910-917), in which the presence of the PEO
      spacer enhances the ET reaction rate. The reduction in the apparent PT
      concentration at the electrode interface due to the high mobility of the PEO
      chain, leading to low efficiency in the formation of an enzyme-mediator complex,
      is a possible reason for the lower mediation ability of PT-PEO1000 than that of
      PT-PA for the ET between the FAD group and PT(+) immobilized on the electrode.
      Inhibition of the penetration of GOx molecules into the monolayer and of the
      accessibility of some part of PT groups to GOx molecules could also be reasons
      for the lower mediation ability of PT-PEO1000 thickly modified on the electrode.

PMID- 15987121
TI  - Determination of bond dissociation energies using electrospray tandem mass
      spectrometry and a derived effective reaction path length approach.
AB  - A new approach for calculating bond dissociation energies (BDEs) from ES-MS/MS
      measurements has been developed. The new method features a "derived effective
      reaction path length" that has been applied to measure BDEs of alkali metal (Li+)
      adducts and halide (Cl-) adducts of monoacylglycerol, 1,2-diacylglycerol, and 1,3
      diacylglycerol lipids. Also studied were lithium-bound dimers of
      monoacylglycerols, 1,2-diacylglycerols, and 1,3-diacylglycerols. BDEs for the
      adducts and dimers of the lipids were derived from collision-induced dissociation
      experiments using a triple quadrupole mass spectrometer with electrospray as the
      ionization source. Mass spectral data were used to empirically derive a single
      exponential growth equation that relates product cross section to collision
      energy. From these single-exponential equations, a general second-order
      polynomial was derived using a multivariate growth curve model that enables
      prediction of BDEs of unknown complexes. Mass spectral results were compared to
      computer-generated bond dissociation energies using Becke-style three-parameter
      density functional theory (B3LYP, employing the Lee-Yang-Parr correlation
      functional), with excellent agreement between experimental and theoretical energy
      values. The newly developed method is general in nature and can be used for the
      measurement of metal or halide ionic adduct bond dissociation energies and for
      the measurement of bond energies of noncovalent interactions such as dimer
      dissociation energies. The validity of the method has been rigorously established
      using a triple quadrupole, but it may also be applied to other mass spectrometers
      that allow user control of the collision cell potential.

PMID- 15987122
TI  - Electron ionization in superimposed magnetic and radio frequency quadrupolar
      electric fields.
AB  - An improved design of a novel electron ionization source for orthogonal
      acceleration time-of-flight mass spectrometry is described, based on the
      superimposition of an axial magnetic field with cylindrical symmetry around a
      radio frequency-only quadrupole. A tubular permanent magnet was designed to
      generate the required strong magnetic field and field profile. An axial electric
      field along the ion guide for efficient ion extraction was introduced using
      segmented quadrupole rods. Details of the source design and the effects of
      various operating parameters are described. The source produces high-quality mass
      spectra with regard to fragmentation, relative abundances, and isotopic ratios.
      Preliminary results have shown excellent sensitivity, with limits of detection in
      the subfemtogram range (octafluoronaphthalene, full spectrum acquisition) in gas
      chromatography/mass spectrometry operation.

PMID- 15987123
TI  - Superimposition of a magnetic field around an ion guide for electron ionization
      time-of-flight mass spectrometry.
AB  - A new electron ionization source was developed for orthogonal acceleration time
      of-flight mass spectrometry (TOFMS) based on the superimposition of a magnetic
      field around a radio frequency-only (rf-only) ion guide. The cylindrically
      symmetric magnetic field compresses the electron beam from the electron source
      into a long narrow volume along the ion guide axis. The magnetic field also helps
      to maintain a narrow energy distribution of electrons that penetrate the full
      length of the ion guide despite the influence of the radial rf field. Ionization
      occurs inside the ion guide with improved efficiency resulting from efficient use
      of electrons, prolonged interaction time, and nontraditionally large ionization
      volume. At the same time, the rf field effectively focuses ions radially and
      confines them to the axis of the ion guide by collisional focusing, leading to
      high ion transmission efficiency. Furthermore, the source can also be operated in
      a trap-and-pulse mode to improve the ion sampling duty cycle of orthogonal
      acceleration TOFMS. To validate the design concept of this new ion source, a
      simple prototype using a single set of cylindrical rods was constructed and
      retrofitted to an orthogonal acceleration TOFMS. A significant increase in ion
      signal intensity was observed by operating the source in a pulsed ion extraction
      mode. Low detection limits (for example, 12 fg for toluene) were determined at
      12.5 spectra s(-1) in the full spectrum mode.

PMID- 15987124
TI  - Application of ion trap-MS with H/D exchange and QqTOF-MS in the identification
      of microbial degradates of trimethoprim in nitrifying activated sludge.
AB  - In this work, the identification of two microbial degradation products of the
      antimicrobial trimethoprim (290 Da) is described. The structural elucidation of
      the metabolites, which were produced by nitrifying activated sludge bacteria in a
      small-scale laboratory batch reactor, was accomplished by electrospray ionization
      ion trap mass spectrometry conducting consecutive fragmentation steps (MS(n))
      combined with H/D-exchange experiments. Although one metabolite corresponded to
      alpha-hydroxytrimethoprim (306 Da), oxidation of the aromatic ring within the
      diaminopyrimidine substructure was determined for the second degradate (324 Da).
      Accurate mass measurements of the two metabolites were provided by a hybrid
      quadrupole time-of-flight-mass spectrometer operated in MS/MS mode. With absolute
      mass errors of <5 mDa, it allowed us to confirm the proposed elemental
      composition for the protonated precursor ions as well as for a series of fragment
      ions that were previously identified by ion trap mass spectrometry. The study
      emphasized the potential of nitrifying activated sludge bacteria for breaking
      down an environmentally relevant pharmaceutical that is otherwise poorly
      degradable by a bacterial community encountered in conventional activated sludge.

PMID- 15987126
TI  - Characterizing dissolved organic carbon using asymmetrical flow field-flow
      fractionation with on-line UV and DOC detection.
AB  - A method of characterizing dissolved organic carbon (DOC) by asymmetrical flow
      field-flow fractionation with on-line UV and DOC detection is described and
      applied to standards and natural water samples. Poly(styrenesulfonate) polymer
      standards, Suwannee River humic standards, and naturally occurring surface water
      and groundwater DOC were analyzed using this coupled detection technique.
      Molecular weight determinations in the samples and standards were 6-30% lower
      with DOC analysis than UV analysis. This difference was attributed to the
      insensitivity of the latter technique to nonaromatic carbon and suggests the
      molecular weight determined with the DOC detector is a more accurate
      representation of the actual molecular weight of the DOC. A normalized intensity
      comparison (NIC) method was proposed to distinguish differences in the relative
      amounts of aromatic and aliphatic carbon in DOC by comparing the two detector
      responses. The NIC method was applied to yield an average aromatic content of the
      bulk DOC and to detail the aromatic content over a range of molecular weights in
      a single DOC fraction.

PMID- 15987125
TI  - Effects of tryptic peptide esterification in MALDI mass spectrometry.
AB  - The effect of esterification on MALDI ion yield is investigated by using alcohols
      having different aliphatic chain lengths. For peptides whose ionization yields
      increase with derivatization, more hydrophobic alcohols tend to yield greater
      peak enhancements. The completeness of the reaction increases from propanol to
      methanol. Undesired solvolysis of the amide group in the side chain of Asn or Gln
      leads to unexpected ester products. Ethanol is suggested as the optimal alcohol
      for esterification in proteomics experiments since it yields almost complete
      esterification without substantial solvolysis. Ethanol esterification was
      employed to facilitate the identification of gel-separated proteins.

PMID- 15987127
TI  - Construction and evaluation of a humic acid column: implication for pesticide
      risk assessment.
AB  - In this paper, humic acid (HA), known to play a large role in the binding and
      transport of pesticides in soil, was immobilized on a chromatographic support.
      Then, the association of some herbicides and rodenticides with the main soil
      component HA was examined using this novel chromatographic column. It appeared
      that HA has a lower affinity for neutral than for charged pesticides. Moreover,
      the influence of various parameters was investigated on the pesticide retention
      in order to providevaluable information about both the binding mechanism and the
      utilization conditions of the HA column. For all the pesticides studied, a change
      was clearly vizualized in the HA-pesticide association mechanism at a critical
      value of the Na+ concentration in the bulk solvent, x(c), equal to 0.6 M. Around
      this value, the HA structure balanced between a flexible linear conformation for
      x < x(c) and a random coil form for x > x(c). This work confirmed the
      conformation change on HA immobilized on silica. As well, only for the charged
      pesticides, it was clearly pointed out that below a Na+ concentration equal to
      0.3 M, the pesticide binding to HA decreased when the salt concentration was
      enhanced due to an ion pair formation and a competition effect between the sodium
      cation and pesticide to bind to the HA molecule. Furthermore, it was established
      that the HA column was stable during an extended period of time, indicating that
      the HA column could soon become very attractive to determine the risk assessment
      of pesticides.

PMID- 15987128
TI  - Hollow fiber flow field-flow fractionation of proteins using a microbore channel.
AB  - Protein separation through hollow fiber flow field-flow fractionation (HF FlFFF)
      at microflow rate regime was successfully achieved by employing a microbore
      hollow fiber. In most of the flow field-flow fractionation (FlFFF) techniques
      applied to the separation of proteins, including hollow fiber FlFFF (HF FlFFF),
      an outflow rate leading to a detector has typically been a few tenths of a
      milliliter per minute. In this study, it is demonstrated for the first time that
      10 microL/min outflow rate in HF FlFFF can be employed for a successful
      separation of proteins by utilizing a small inner diameter (450 microm) hollow
      fiber. Initial evaluations of microbore HF FlFFF separation were made to improve
      separation efficiency by evaluating plate heights, sample recovery, and the limit
      of detection using protein standards. Microbore HF FlFFF was applied for the
      separation of low-abundance blood proteins depleted of high-abundance proteins
      from raw serum using immunoaffinity chromatography.

PMID- 15987129
TI  - Fractal dimension analysis of time-resolved diffusely scattered light from turbid
      samples.
AB  - To improve quantification of optical properties in highly scattering and
      absorbing samples, time-correlated single photon counting measurements were
      analyzed using quantities related to the correlation dimension. Photon time-of
      flight (TOF) distributions were collected in reflection and transmission optical
      configurations from samples made of cream and water-soluble dye (0 < mu(a) < 0.05
      mm(-1); 100 < mu(s) < 250 mm(-1)). It was found that absorption and scattering
      properties of samples could be accurately quantified from information used to
      determine the correlation dimension. Scattering coefficients were estimated with
      less than 4% error for both optical configurations. Absorption estimates were
      made with CVs of 7.5 and 9.6% for reflection and transmission, respectively.
      Overall, fractal dimension analysis of TOF distributions provides a simple method
      of determining the optical properties of a sample.

PMID- 15987130
TI  - Glyphosate immunosensor. Application for water and soil analysis.
AB  - A fully automated immunosensor for the herbicide glyphosate has been developed on
      the basis of the immunocomplex capture assay protocol. The sensor carries out on
      line analyte derivatization prior to the assay and uses a selective anti
      glyphosate serum, a glyphosate peroxidase enzyme tracer, and fluorescent
      detection. Under optimal conditions, the detection limit achieved is 0.021
      microg/L with an analysis rate of 25 min per assay, autonomy of more than 48 h,
      and sensor reusability >500 analytical cycles. The immunosensor is able to
      discriminate structurally related molecules, such as aminomethylphosphonic acid,
      the main metabolite of glyphosate, and other related herbicides, such as
      glufosinate and glyphosine. Interferences from naturally occurring species
      (anions, cations, and humic substances) and their elimination were also studied.
      The immunosensor has been successfully applied to water and soil sample analysis,
      with good recoveries at levels lower than 1 microg/L. Results obtained with the
      immunosensor correlate well with data from a magnetic particle ELISA and LC/LC/MS
      chromatographic method.

PMID- 15987131
TI  - Discriminative detection of volatile sulfur compound mixtures with a plasma
      polymerized film-based sensor array installed in a humidity-control system.
AB  - We demonstrated the discrimination of volatile sulfur compound mixtures with
      different mixing ratios by using an array of the plasma-polymerized film (PPF)
      coated quartz crystal resonators. The PPF sensor array, which contains PPFs
      prepared from amino acids and synthetic polymers, exhibited different response
      patterns to mono or mixed volatile sulfur compounds (VSCs) (hydrogen sulfide and
      methanethiol) under a dry environment. The sensor array was installed in a
      desktop-size relative humidity controller. The relative humidity and temperature
      conditions of the sample flow to the sensor cell were equalized to those of the
      inner atmosphere of the sensor cell based on the concept of the two-separate
      temperatures method. In this way, the baseline drift of PPF sensor response
      caused by the introduction of a highly humid sample was successfully suppressed.
      We compared the sensor array responses under the controlled humidity conditions.
      Presorption of water molecules by PPFs caused a decrease of sensor sensitivity,
      but the films still had the ability to discriminate sub-ppmv VSC mixtures having
      6:1, 1:1, and 1:6 mixture ratios of hydrogen sulfide and methanethiol.

PMID- 15987132
TI  - Electrochemical enzyme immunoassay of a peptide hormone at picomolar levels.
AB  - A novel electrochemical enzyme immunoassay system with a 10 ng L(-1) level
      detection limit was developed for the determination of B-type natriuretic peptide
      (BNP), an important marker for the diagnosis of heart failure. Sample BNP was
      added to a solution containing a certain concentration of
      acetylcholinesterase(AChE)-labeled anti-BNP antibody to undergo an immunological
      reaction. After the immunological reaction, we proposed two assay schemes. One
      involves measuring the amount of antibody-enzyme conjugate that reacted with two
      BNP molecules (reacted conjugate). The other involves measuring the amount of
      antibody-enzyme conjugate with at least one free binding site (unreacted
      conjugate). Then the amount of reacted or unreacted conjugate was determined by
      measuring the AChE activity after the recovery of each conjugate from the
      immunological reaction mixture. To determine the trace level of the recovered
      antibody-enzyme conjugate, the AChE activity was determined with high sensitivity
      on the basis of the chemisorption/electrochemical desorption process of
      thiocholine, which was produced through the enzymatic reaction, on a silver
      surface. The thiocholine chemisorption (i.e., accumulation) on the silver
      electrode surface resulted in a sensitivity for the electrochemical determination
      of the AChE activity that was 2 orders of magnitude greater than that obtained
      when using direct measurement without accumulation. The procedure for determining
      the AChE activity of unreacted conjugate after its recovery on a BNP-modified
      disk was applied to the determination of BNP in serum samples. This procedure
      involves the removal of the immunological reaction mixture before the enzymatic
      reaction process, which allows the AChE activity to be measured without any
      interference from endogenous pseudocholinesterase, which exists with high
      activity in serum. With both procedures, the BNP could be measured within an
      hour. The detection limits were 20 and 40 ng L(-1) using the reacted and
      unreacted conjugate measuring procedures, respectively.

PMID- 15987133
TI  - Supercritical fluid extraction of energetic nitroaromatic compounds and their
      degradation products in soil samples.
AB  - This paper explores the use of supercritical fluid extraction (SFE), in
      combination with various analyte collection strategies, for extracting energetic
      nitroaromatic compounds and their degradation products from soil samples. The
      required selectivity has been achieved by a combination of an SFE program and
      active trapping. Several different collection strategies were tested, using a
      selection of liquids (methanol, toluene, methyl tert-butyl ether, acetonitrile),
      inert and solid-phase extraction materials (Nexus, Oasis, LiChrolut), and 1-cm
      liquid chromatography precolumns (porous graphitic carbon, PGC). The best results
      were obtained using SFE in combination with a PGC precolumn. This setup allows on
      line cleanup of the extract, and comparable results were obtained using either GC
      ECD or GC-chemical ionization-MS for confirmatory analysis. The time required for
      a complete analysis was less than 60 min, and only 1 mL of toluene was needed for
      a 0.5-g representative sample. In contrast, the EPA standard method 8330 required
      18-h sonication and 20 mL of acetonitrile for a 4.0-g sample and further time for
      sample cleanup and HPLC analysis. The method presented here provides method
      detection limits in the low-nanogram range, with relative standard deviations
      lower than 7%. The optimized method has been compared and validated with EPA
      method 8330 in terms of efficiency parameters such as robustness, accuracy
      (trueness and precision), and capability of detection. The validation
      demonstrated that the two analytical methodologies give comparable performance
      for the determination of nitroaromatic compounds, but SFE is superior for
      analyzing amine degradation products.

PMID- 15987134
TI  - Selection of ligands for affinity chromatography using quartz crystal biosensor.
AB  - This paper described a new strategy for rapid selecting ligands for application
      in affinity chromatography using a quartz crystal microbalance (QCM) biosensor.
      An aminoglycoside antibiotic drug, kanamycin (KM), was immobilized on the gold
      electrodes of the QCM sensor chip. The binding interactions of the immobilized KM
      with various proteins in solution were monitored as the variations of the
      resonant frequency of the modified sensor. Such a rapid screen analysis of
      interactions indicated clearly that KM-immobilized sensor showed strong specific
      interaction only with lysozyme (LZM). The resultant sensorgrams were rapidly
      analyzed by using a kinetic analysis software based on a genetic algorithm to
      derive both the kinetic rate constants (k(ass) and k(diss)) and equilibrium
      dissociation constants (K(D)) for LZM-KM interactions. The immobilized KM showed
      higher affinity to LZM with a dissociation constant on the order of 10(-5) M,
      which is within the range of 10(-4)-10(-8) M and suitable for an affinity ligand.
      Therefore, KM was demonstrated for the first time as a novel affinity ligand for
      purification of LZM and immobilized onto the epoxy-activated silica in the
      presence of a high potassium phosphate concentration. The KM immobilized affinity
      column has proved useful for a very convenient purification of LZM from chicken
      egg white. The purity of LZM obtained was higher than 90%, as determined by
      densitometric scanning of sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of purified fraction. These results confirmed that the selected
      KM ligand is indeed a valuable affinity ligand for purification of LZM. The new
      screening strategy based on a QCM biosensor is expected to be a promising way for
      rapid selecting specific ligands for purifying other valuable proteins.

PMID- 15987135
TI  - Adsorption mechanism in RPLC. Effect of the nature of the organic modifier.
AB  - The adsorption isotherms of phenol and caffeine were acquired by frontal analysis
      on two different adsorbents, Kromasil-C18 and Discovery-C18, with two different
      mobile phases, aqueous solutions of methanol (MeOH/H2O = 40/60 and 30/70, v/v)
      and aqueous solutions of acetonitrile (MeCN/H2O = 30/70 and 20/80, v/v). The
      adsorption isotherms are always strictly convex upward in methanol/water
      solutions. The calculations of the adsorption energy distribution confirm that
      the adsorption data for phenol are best modeled with the bi-Langmuir and the tri
      Langmuir isotherm models for Kromasil-C18 and Discovery-C18, respectively.
      Because its molecule is larger and excluded from the deepest sites buried in the
      bonded layer, the adsorption data of caffeine follow bi-Langmuir isotherm model
      behavior on both adsorbents. In contrast, with acetonitrile/water solutions, the
      adsorption data of both phenol and caffeine deviate far less from linear
      behavior. They were best modeled by the sum of a Langmuir and a BET isotherm
      models. The Langmuir term represents the adsorption of the analyte on the high
      energy sites located within the C18 layers and the BET term its adsorption on the
      low-energy sites and its accumulation in an adsorbed multilayer system of
      acetonitrile on the bonded alkyl chains. The formation of a complex adsorbed
      phase containing up to four layers of acetonitrile (with a thickness of 3.4 A
      each) was confirmed by the excess adsorption isotherm data measured for
      acetonitrile on Discovery-C18. A simple interpretation of this change in the
      isotherm curvature at high concentrations when methanol is replaced with
      acetonitrile as the organic modifier is proposed, based on the structure of the
      interface between the C18 chains and the bulk mobile phase. This new model
      accounts for all the experimental observations.

PMID- 15987136
TI  - Polylysine-coated diamond nanocrystals for MALDI-TOF mass analysis of DNA
      oligonucleotides.
AB  - A protocol based on aminated diamond nanocrystals has been developed to isolate,
      concentrate, purify, and digest DNA oligonucleotides in one microcentrifuge tube
      for matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass
      spectrometry. It is shown that use of diamond nanocrystals as a solid-phase
      extraction support not only permits concentration of oligonucleotides in highly
      diluted solutions but also facilitates separation of oligonucleotides from
      proteins in heavily contaminated solutions. Enzymatic digestions can be conducted
      on particle, and additionally, the digests can be easily recovered from the
      solution for base sequencing. In this method, the aminated diamond nanocrystals (
      approximately 100 nm in diameter) were prepared by noncovalent coating of
      carboxylated/oxidized diamonds with poly(L-lysines) (PL), which form stable
      complexes with DNA oligonucleotides. While the complexes are sufficiently stable
      to sustain repeated washing with deionized water, the DNA molecules can be
      readily eluted after incubation of the diamond adducts in aqueous ammonium
      hydroxide at elevated temperatures. No preseparation of PL or diamond
      nanocrystals is required for subsequent MALDI-TOF mass analysis.

PMID- 15987137
TI  - On-chip transformation of bacteria.
AB  - On-chip transformation of Escherichia coli cells was accomplished for the first
      time using a microbial array chip. The continuous E. coli transformation
      procedures were performed on a chip in which the microcompartment was composed of
      PDMS microfluidic channels and a silicon substrate predeposited with different
      plasmid DNAs. The PDMS microfluidic device enabled the parallel transformation of
      E. coli cells with various plasmid DNAs by separating each transformation area.
      The phenotypic differences reflecting different plasmid DNAs were identified by
      various approaches such as colorimetry, fluorometry, and electrochemical methods.
      This microbial array chip could become a versatile tool for many cell biological
      applications.

PMID- 15987138
TI  - SPR sensor chip for detection of small molecules using molecularly imprinted
      polymer with embedded gold nanoparticles.
AB  - Molecularly imprinted polymer gel with embedded gold nanoparticle was prepared on
      a gold substrate of a chip for a surface plasmon resonance (SPR) sensor for
      fabricating an SPR sensor sensitive to a low molecular weight analyte. The
      sensing is based on swelling of the imprinted polymer gel that is triggered by an
      analyte binding event within the polymer gel. The swelling causes greater
      distance between the gold nanoparticles and substrate, shifting a dip of an SPR
      curve to a higher SPR angle. The polymer synthesis was conducted by radical
      polymerization of a mixture of acrylic acid, N-isopropylacrylamide, N,N'
      methylenebisacrylamide, and gold nanoparticles in the presence of dopamine as
      model template species on a sensor chip coated with allyl mercaptan. The modified
      sensor chip showed an increasing SPR angle in response to dopamine concentration,
      which agrees with the expected sensing mechanism. Furthermore, the gold
      nanoparticles were shown to be effective for enhancing the signal intensity (the
      change of SPR angle) by comparison with a sensor chip immobilizing no gold
      nanoparticles. The analyte binding process and the consequent swelling appeared
      to be reversible, allowing one the repeated use of the presented sensor chip.

PMID- 15987139
TI  - Flavin adenine dinucleotide as precursor for NADH electrocatalyst.
AB  - The generation of a new electrocatalytic system for NADH after oxidizing flavin
      adenine dinucleotide (FAD) is shown. The oxidation is performed in alkaline
      medium until +1.4 V (Ag/AgCl) at graphite electrodes. The catalytic activity is
      ascribed to the electrooxidized moiety of FAD and not to quinone surface groups.
      A comparison between this catalyst and that attributed to poly(FAD) (Karyakin, A.
      A.; Ivanova Y. N.; Revunova, K. V.; Karyakina, E. E. Anal. Chem. 2004, 76, 2004
      2009.) is presented. It is concluded that the surface quinone groups generated
      during the strong anodization of the electrode in acidic medium at 2-2.5 V and
      not the poly(FAD) are responsible for the catalytic activity described in the
      above mentioned work.

PMID- 15987140
TI  - Comment on "vibrational spectroscopic analysis of silicones: a fourier transform
      Raman and inelastic neutron scattering investigation".

PMID- 15987141
TI  - Interaction of fullerenes with the concave surfaces of perchloroazatriquinacene.
AB  - [reaction: see text] Crystal structures of the one-to-one co-crystals of
      C(60).perchloroazatriquinacene and C(70).perchloroazatriquinacene show that the
      rigid, chalice-like azatriquinacene packs between completely ordered fullerene
      molecules with multiple, close Cl...fullerene contacts.

PMID- 15987142
TI  - Effect of guest molecule flexibility in access to dendritic interiors.
AB  - [structure: see text] Dendrimers are attractive scaffolds for catalysis, since
      catalytic sites can be isolated and the catalysts are recoverable and reusable.
      Herein, we show that conformationally constrained molecules have better access to
      dendritic cores compared to the more flexible counterparts. The results reported
      here should have implications in utilizing dendrimers as scaffolds for artificial
      selectivity in catalysis.

PMID- 15987143
TI  - Bis-diazeniumdiolates of dialkyldiamines: enhanced nitric oxide loading of parent
      diamines.
AB  - [reaction: see text] The synthesis and characterization of a series of symmetric
      bis-dialkyldiamine-based diazeniumdiolates, RN[N(O)NO(
      )Na(+)](CH(2))(x)()N[N(O)NO(-)Na(+)]R', are reported. Preparation of
      corresponding intramolecular diazeniumdiolates of the form RN[N(O)NO](
      )(CH(2))(x)()NH(2)(+)R' with alkyl groups > (CH(2))(4)CH(3) have been shown
      previously to lack stability. In contrast, sodium-stabilized bis
      diazeniumdiolates of such lipophilic species can be readily formed when these
      same diamines are reacted with NO in basic media. The resulting compounds release
      4 mol of NO per mole of original diamine. This approach enables the synthesis of
      more lipophilic NO donors than previously possible.

PMID- 15987144
TI  - Biogenetically inspired enantioselective approach to Indolo[2,3-a]- and
      benzo[a]quinolizidine alkaloids from a synthetic equivalent of secologanin.
AB  - [reaction: see text] Racemic oxodiester 1 undergoes stereoselective
      cyclocondensation with (S)-tryptophanol, (S)-(3,4-dimethoxyphenyl)alaninol, or
      the corresponding amino acids, in a process involving a tandem dynamic kinetic
      resolution/desymmetrization of diastereotopic groups, to give bicyclic lactams,
      which are cyclized to substituted indolo[2,3-a]- and benzo[a]quinolizidines.

PMID- 15987145
TI  - Asymmetric synthesis of trans-3,4-dialkyl-gamma-butyrolactones via an acyl
      Claisen and iodolactonization route.
AB  - [reaction: see text] A new, efficient, and general asymmetric synthesis of
      enantiomerically pure trans-3,4-dialkyl-gamma-lactones has been developed. The
      key steps are (1) copper-catalyzed three-component coupling of chiral amine,
      aldehyde, and alkyne, (2) acyl-Claisen rearrangement, and (3) iodolactonization.
      The products, chiral gamma-lactones, are versatile synthetic intermediates and
      structural units of natural products and modified nucleosides.

PMID- 15987146
TI  - Toward improving the chemistry of N-acyliminium ions: nucleophilic substitution
      reactions of pyrrolidinone derivatives with trialkylsilyl nucleophiles catalyzed
      by triisopropylsilyltrifluoromethane sulfonate (TIPSOTf).
AB  - [reaction: see text] Nucleophilic substitution reactions of racemic and chiral 5
      acetoxy-, 5-ethoxy-, and 5-methoxypyrrolidin-2-ones by silicon-based nucleophiles
      were efficiently catalyzed by TIPSOTf. This process was found to be general and
      accommodates a broad range of substrate-nucleophile combinations.

PMID- 15987147
TI  - Novel glassy tetra(N-alkyl-3-bromocarbazole-6-yl)silanes as building blocks for
      efficient and nonaggregating blue-light-emitting tetrahedral Materials.
AB  - [structure: see text] Tetrahedral precursors of tetra(N-alkyl-3-bromocarbazole-6
      yl)silanes (1-3), which were amorphous with T(g) being adjustable by changing the
      chain length of the N-substitutent, were developed. Fluorene-conjugated glassy
      compound 4 and hyperbranched polymer 5 were synthesized from the precursors via
      Suzuki coupling reaction. 4 and 5 emitted blue light efficiently in the condensed
      state with high quantum efficiencies of 80 (4) and 59% (5) and small fwhm (full
      width at half-maximum) of 48 (4) and 55 nm (5), indicating that they did not pack
      into detrimental aggregates in the solid state.

PMID- 15987148
TI  - Cobalt(II)-catalyzed intermolecular Diels-Alder reaction of piperine.
AB  - [reaction: see text] An intermolecular cobalt-phosphine-catalyzed Diels-Alder
      reaction of piperine is described. The dimerization of piperine in the presence
      of cobalt-phosphine complexes gave much better yields than that in the presence
      of only cobalt, which, combined with the result under the purely thermal
      conditions, indicates that addition of phosphine ligands changes the inhibition
      of cobalt to the reaction into promotion. For elucidation of the distinction,
      different cobalt-catalyzed mechanisms were proposed for the Diels-Alder
      dimerization of piperine.

PMID- 15987149
TI  - Stereoselective syntheses of the bioactive polypropionates aureothin, N
      acetylaureothamine, and aureonitrile.
AB  - [reaction: see text] Concise total syntheses of the bioactive polypropionates
      aureothin, N-acetylaureothamine, and aureonitrile are described.

PMID- 15987150
TI  - Synthesis of 1,10-dimethylbicyclo[8.8.8]hexacosane and 1,10
      dihydroxybicyclo[8.8.8]hexacosane.
AB  - [structure: see text] 1,10-Dimethylbicyclo[8.8.8]hexacosane (1) and 1,10
      dihydroxybicyclo[8.8.8]hexacosane (2) were prepared in 4% yield over seven steps
      and in 18% yield over three steps, respectively, starting from 1,10
      cyclooctadecanedione. The identities and out,out conformations of these compounds
      were established by single-crystal X-ray analysis.

PMID- 15987151
TI  - The mechanism of photoinduced acylation of amines by N-acyl-5,7-dinitroindoline
      as determined by time-resolved infrared spectroscopy.
AB  - [reaction: see text] The photochemistry of N-acyl-5,7-dinitroindoline (1) was
      studied in acetonitrile using nanosecond time-resolved infrared (TRIR)
      spectroscopy. Upon photolysis, two nearly but not completely overlapping sets of
      transient IR bands are observed that are assigned to two non-interconvertible
      conformers of mixed acetic nitronic anhydride 7. While syn-7 reverts rapidly to
      1, anti-7 is long-lived and is able to acylate amines. Results of density
      functional theory calculations support conclusions based on experimental TRIR
      data.

PMID- 15987152
TI  - Allocolchicinoid synthesis via direct arylation.
AB  - [reaction: see text] A formal enantioselective synthesis of allocolchicine and a
      synthesis of a C-ring analogue have been achieved by employing an intramolecular
      direct arylation of an aryl chloride to form the biaryl carbon-carbon bond and
      the seven-membered ring.

PMID- 15987153
TI  - Template-directed DNA photoligation via alpha-5-cyanovinyldeoxyuridine.
AB  - [reaction: see text] We describe an efficient template-directed photoligation of
      oligodeoxynucleotides (ODNs) using alpha-5-cyanovinyldeoxyuridine (alpha(C)U). An
      efficient photoligation was produced by photoirradiation of an ODN containing
      alpha(C)U at the 3' end with an ODN containing thymine at the 5' end in the
      presence of a template ODN. This photoligation method is a new and efficient way
      to synthesize branched ODNs.

PMID- 15987154
TI  - Single molecular multianalyte sensor: jewel pendant ligand.
AB  - [structure: see text] The jewel pendant ligand has multiple chromogenic units
      combined in a single molecule with the dyes linked to a semiselective binding
      site by three heteroatoms (O, N, S) having different HSAB characteristics, to
      indicate diverse response to individual transition metal ions. Using a single
      molecular multianalyte sensor, multiple analytes could be determined with a
      minimal sensing system.

PMID- 15987155
TI  - Synthesis of a pipecolic acid-based bis-amino acid and its assembly into a spiro
      ladder oligomer.
AB  - [reaction: see text] The synthesis of a new pipecolic acid-based bis-amino acid
      building block 1 (and 2) is presented. Assembly of this monomer into a spiro
      ladder oligomer 3 utilizing solid-phase synthesis followed by in situ activation
      by dicyclohexylcarbodiimide and N-hydroxysuccinimide has been demonstrated. The
      structure of oligomer 3, determined in aqueous solution using two-dimensional
      NMR, reveals that the oligomer forms a left-handed helix and that each monomer
      unit adopts a chair conformation.

PMID- 15987156
TI  - Substitution of benzylic hydroxyl groups with vinyl moieties using vinylboron
      dihalides.
AB  - [reaction: see text] Substitution of benzylic hydroxyl groups with vinyl moieties
      using vinylboron dihalides has been achieved. The reaction provides a novel
      method for preparing stereodefined alkenyl halides.

PMID- 15987157
TI  - Enantiopure sulfinyl azobenzenes as chiroptical switches.
AB  - [reaction: see text] Photoswitchable enantiopure sulfinyl azo compounds have been
      synthesized. A remarkable perturbation of the azo system by the stereogenic
      sulfinyl moiety has been observed by CD in both the trans and the cis azobenzenes
      resulting by photoisomerization. After five irradiation cycles, the
      configurational integrity of these chiral switches remains unchanged.

PMID- 15987158
TI  - Synthesis and biological evaluation of (-)-16-normethyldictyostatin: a potent
      analogue of (-)-dictyostatin.
AB  - [structure: see text] (-)-16-Normethyldictyostatin has been made by total
      synthesis and is a potent antitumor agent in cells expressing wild-type tubulin
      and in one mutant cell line that is resistant to paclitaxel, but it is much less
      active than dictyostatin in another paclitaxel-resistant cell line where Val is
      substituted for Phe270. This provides strong evidence that the C16 methyl group
      of the dictyostatins is oriented toward Phe270 in the paclitaxel-binding site on
      beta-tubulin.

PMID- 15987159
TI  - Compound representatives of a new type of triterpenoid from Aglaia odorata.
AB  - [structure: see text] A novel triterpenoid, 21,25-cyclodammar-20(22)-ene
      3beta,24alpha-diol, has been isolated from Aglaia odorata. Its structure was
      elucidated on the basis of 1D- and 2D-NMR and MS spectra and then confirmed by X
      ray diffraction. It represents a new type of natural five-membered-ring
      triterpenoid, named cyclodammarane. Its possible biopathway was that squalene
      2,3;22,23-diepioxide was directly cyclized to form 24,25-epoxydammar-20(21)-en-3
      ol, followed by protonation of the remaining 24,25-epoxide and the cation
      attacking 21(20) methylene to generate the E ring.

PMID- 15987160
TI  - Applications of 4,4'-(Me3Si)2-BINAP in transition-metal-catalyzed asymmetric
      carbon-carbon bond-forming reactions.
AB  - [structure: see text] A recently developed BINAP derivative with trimethylsilyl
      substituents on the 4- and 4'-positions of the binaphthyl skeleton, 2,2'
      bis(diphenylphosphino)-4,4'-bis(trimethylsilyl)-1,1'-binaphthyl (tms-BINAP), was
      used in a variety of transition-metal-catalyzed asymmetric carbon-carbon bond
      forming reactions. In pi-allylpalladium-mediated reactions, tms-BINAP gave better
      enantioselectivity than the unsubstituted BINAP, and the origin of the improved
      enantioselectivity was gained from an X-ray structural study of [Pd(eta(3)
      C(3)H(5))((R)-tms-BINAP)]ClO(4).

PMID- 15987161
TI  - Water-soluble green perylenediimide (PDI) dyes as potential sensitizers for
      photodynamic therapy.
AB  - [reaction: see text] A series of water-soluble green perylenediimide (PDI) dyes
      have been synthesized. On red light excitation, these dyes were shown to be
      efficient generators of singlet oxygen, and in cell culture media, they were
      shown to display significant light-induced cytotoxic effects on the human
      erythroleukemia cell line (K-562). It appears that highly versatile PDI dyes are
      likely to find new applications in photodynamic therapy.

PMID- 15987162
TI  - Recyclable self-assembly-supported catalytic system for orthoalkylation.
AB  - [reaction: see text] A new recyclable supported catalyst system for
      orthoalkylation was devised using a self-assembly consisting of the barbiturate
      and 2,4,6-triaminopyrimidine H-bonding motifs. At high temperature, the system is
      completely homogeneous so as to give an efficient catalytic activity, while it is
      heterogenized at room temperature to form an insoluble solid phase for the easy
      recovery of the catalyst after the reaction.

PMID- 15987163
TI  - Effects of complexation with 18-crown-6 on the hypernucleofugality of phenyl
      lambda3-iodanyl groups. Synthesis of vinyl-lambda3-iodane.18-crown-6 complex.
AB  - [structure: see text] 4-tert-Butyl-1-cyclohexenyl(phenyl)(tetrafluoroborato)
      lambda(3)-iodane forms a discrete supramolecular complex by the reaction with 18
      crown-6. Solvolysis of the cyclohexenyl-lambda(3)-iodane in the presence of 18
      crown-6 indicates that the complexation with 18-crown-6 tends to decrease the
      leaving group ability of hypervalent phenyl-lambda(3)-iodanyl groups.

PMID- 15987164
TI  - Oceanalin A, a hybrid alpha,omega-bifunctionalized sphingoid
      tetrahydroisoquinoline beta-glycoside from the marine sponge Oceanapia sp.
AB  - [reaction: see text] The novel antifungal compound oceanalin A, an unprecedented
      "hybrid sphingolipid", was isolated from the marine sponge Oceanapia sp. The
      structure was elucidated using NMR and MS spectral analysis and chemical
      degradation. Oceanalin A exhibits in vitro antifungal activity against Candida
      glabrata with an MIC of 30 mug/mL.

PMID- 15987165
TI  - Biomimetic synthesis of elysiapyrones A and B.
AB  - [reaction: see text] The total synthesis of bicyclo[4.2.0]octane natural products
      elysiapyrones A and B is described.

PMID- 15987166
TI  - Configuration of the psymberin amide side chain.
AB  - [structure: see text] The structure of the amide side chain of psymberin, a
      potent and selective cytotoxin, is proposed. Syn and anti models of the amide
      side chain were prepared, and the structural assignment was confirmed by X-ray
      crystallographic analysis of the anti isomer. Comparison of (1)H and (13)C NMR
      data establishes homology between the natural product and the synthetic model
      compound of anti configuration and not the corresponding syn isomer.

PMID- 15987167
TI  - Nickel-catalyzed addition of P(O)-H bonds to propargyl alcohols: one-pot
      generation of phosphinoyl 1,3-butadienes.
AB  - [reaction: see text] Diphenylphosphine oxide and related P(O)H compounds react
      with propargyl alcohols at room temperature in the presence of a catalytic amount
      of Ni(0) complex and Ph(2)P(O)OH to produce high yields of phosphinoyl 1,3-dienes
      though an efficient in situ dehydration process.

PMID- 15987168
TI  - Synthesis of pentafluorophenylmethylamines via silicon Mannich reaction.
AB  - [reaction: see text] The three-component coupling of aldehydes, secondary amines,
      and methoxytris(pentafluorophenyl)silane, MeOSi(C(6)F(5))(3), affording
      pentafluorophenylmethylamines has been described. The generation of the five
      coordinate silicate intermediate is believed to be the key feature responsible
      for the efficiency of the reaction.

PMID- 15987170
TI  - Highly efficient route to o-Allylbiaryls via palladium-catalyzed three-component
      coupling of benzynes, allylic halides, and aryl organometallic reagents.
AB  - [reaction: see text] o-Allylbiaryl derivatives have been prepared in good to
      excellent yields by the palladium-catalyzed three-component reaction of allyl
      halides, benzynes, and aryl organometallic reagents.

PMID- 15987169
TI  - A novel stereocontrolled approach to eudesmanolides: total synthesis of (+/-)
      gallicadiol and (+/-)-isogallicadiol.
AB  - [reaction: see text] A novel approach for the stereocontrolled synthesis of
      eudesmanolides was developed based on a quasi-biomimetic strategy starting from a
      functionalized oxabicyclic template, as shown above, by which the first total
      syntheses of gallicadiol (6) and isogallicadiol (7) were achieved. The key
      elements of the synthesis include: (1) a facile and stereospecific synthesis of a
      functionalized epoxy aldehyde intermediate; (2) a mild Lewis acid-mediated
      stereoselective ene cyclization; and (3) a stereocontrolled gamma-lactonization.

PMID- 15987171
TI  - An approach to the isoschizozygane alkaloid core using a 1,4-dipolar
      cycloaddition of a cross-conjugated heteroaromatic betaine.
AB  - [reaction: see text] A new strategy for the synthesis of the isoschizozygane
      alkaloid core has been developed that is based on a 1,4-dipolar cycloaddition
      reaction of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct
      undergoes loss of COS, and further reduction delivers a 5a-aza-acenaphthylene
      intermediate that was transformed into the isoschizozygane skeleton upon
      treatment with acid.

PMID- 15987172
TI  - Stereoselective synthesis of premisakinolide A, the monomeric counterpart of the
      marine 40-membered dimeric macrolide misakinolide A.
AB  - [structure: see text] The first synthesis of premisakinolide A, the monomeric
      counterpart of misakinolide A, the marine 40-membered macrolide displaying potent
      activity against a variety of human carcinoma cell lines, has been reported. The
      strategy was highlighted by a crucial coupling of a tetrahydropyran fragment and
      an alkynylaluminum reagent having a polypropionate chain, the highly
      stereoselective cross aldol reaction of segment A and segment B, and the
      stereospecific construction of the polypropionate structure based on original
      acyclic stereocontrol.

PMID- 15987173
TI  - In situ generation of o-iodoxybenzoic acid (IBX) and the catalytic use of it in
      oxidation reactions in the presence of Oxone as a co-oxidant.
AB  - [structure: see text] Catalytic use of o-iodoxybenzoic acid (IBX) in the presence
      of Oxone as a co-oxidant is demonstrated for the oxidation of primary and
      secondary alcohols in user- and eco-friendly solvent mixtures. Also demonstrated
      is the in situ (re)oxidation of 2-iodosobenzoic acid (IBA) and even commercially
      available 2-iodobenzoic acid (2IBAcid) by Oxone to IBX allowing one to use these
      less hazardous reagents, in place of potentially explosive IBX, as catalytic
      oxidants.

PMID- 15987175
TI  - Universal strategy for the immobilization of chiral dirhodium catalysts.
AB  - [reaction: see text] Chiral rhodium(II) catalysts used in asymmetric carbenoid
      chemistry can be efficiently heterogenized using a novel immobilization strategy.
      The immobilized catalysts display similar reactivity and stereoselectivity to
      their homogeneous counterparts and can be effectively recycled with limited loss
      in stereoselectivity.

PMID- 15987174
TI  - anti-1,2-Diols via Ni-catalyzed reductive coupling of alkynes and alpha
      oxyaldehydes.
AB  - [reaction: see text] Ni-catalyzed reductive coupling of aryl alkynes (1) and
      enantiomerically enriched alpha-oxyaldehydes (2) afford differentiated anti-1,2
      diols (3) with high diastereoselectivity and regioselectivity, despite the fact
      that the methoxymethyl (MOM) and para-methoxybenzyl (PMB) protective groups
      typically favor syn-1,2-diol formation in carbonyl addition reactions of this
      family of aldehydes.

PMID- 15987177
TI  - Ring expansion of azetidinium ylides: rapid access to the pyrrolizidine alkaloids
      turneforcidine and platynecine.
AB  - [reaction: see text] Azetidinecarboxylate esters react readily with
      metallocarbenes in an inter- or intramolecular fashion to generate azetidinium
      ylides. Efficient [1,2]-shift by the ester-substituted carbon furnishes ring
      expanded pyrrolidine products. In the case of substrate 1, this provides access
      to the pyrrolizidine alkaloids turneforcidine and platynecine via a high-yield,
      five-step sequence starting with readily available methyl 1-benzylazetidine-2
      carboxylate.

PMID- 15987176
TI  - Diastereoselective synthesis of tetrahydrofurans via reaction of gamma,delta
      epoxycarbanions with aldehydes.
AB  - [reaction: see text] Hydroxymethyl-substituted tetrahydrofurans were prepared
      with high diastereoselectivity by reaction of the carbanion derived from 3,4
      epoxybutyl phenyl sulfone with aldehydes in the presence of a mixture of lithium
      and potassium tert-butoxides. Initial formation of aldol-type adducts is a
      nondiastereoselective but reversible process; thus, subsequent formation of one
      main diastereoisomer is controlled by the relative rates of cyclization. The
      configuration of the carbon stereocenter at the oxirane ring is inverted in the
      course of the S(N)2 process, and two new centers are created
      diastereoselectively.

PMID- 15987179
TI  - Stereoselective 4-benzyloxybut-2-enylation of aldehydes via an allyl-transfer
      reaction using a chiral allyl donor.
AB  - [reaction: see text] A direct and highly stereoselective (E)-4-benzyloxybut-2
      enylation of aldehydes was successfully carried out to give 5
      benzyloxyhomoallylic alcohol (11) via an allyl-transfer reaction using a chiral
      allyl donor (10). The chiral allyl donor (10) was prepared by catalytic Sharpless
      asymmetric epoxidation of 3-methylbut-2-en-1-ol, followed by a stereospecific
      vinyl Grignard reaction of the epoxide in the presence of CuBr and selective
      benzylation of the primary alcohol of diol.

PMID- 15987178
TI  - Heptapeptide mimic of ohmefentanyl binding in the discontinuous mu-opiod
      receptor.
AB  - [reaction: see text] Ohmefentanyl binds to the rat mu-opiod receptor via two
      dipeptide sequences (Trp-His and Asp-Tyr) that are separated by 170 residues. A
      turn-inducing tripeptide, Pro-Aib-Aib, holds the dipeptides in a conformation
      that binds the narcotic (K(b) = 7.1 x 10(4) M(-)(1)) in THF. Binding is specific
      for ohmefentanyl over morphine and is accompanied by a conformational change in
      the heptapeptide host. Control experiments with a Gly-Gly-Gly tripeptide linking
      the dipeptides show no evidence of binding.

PMID- 15987180
TI  - Ring-closing alkyne metathesis approach toward the synthesis of alkyne mimics of
      thioether A-, B-, C-, and DE-ring systems of the lantibiotic nisin Z.
AB  - [reaction: see text] Ring-closing alkyne metathesis toward the synthesis of the
      alkyne-brigded A-, B-, C-, and (D)E-ring mimics of the peptide antibiotic nisin Z
      is described. We have successfully synthesized alkyne-bridged cyclic peptides
      containing 4-7 amino acid residues in yields ranging from 18 to 82%.

PMID- 15987181
TI  - Gram-scale synthesis of (-)-epibatidine.
AB  - [reaction: see text] A gram-scale approach toward (-)-epibatidine (1, naturally
      occurring enantiomer), a novel class of amphibian alkaloid, has been developed
      from readily available starting materials using mild and easily controlled
      reactions. The entire synthetic route is straightforward and convenient for gram
      scale synthesis.

PMID- 15987182
TI  - Reactivity-gated photochromism of 1,2-dithienylethenes for potential use in
      dosimetry applications.
AB  - [reaction: see text] A novel molecular switching system based on reactivity-gated
      photochromism operates because a butadiene undergoes a [4 + 2] cycloaddition
      reaction with a dienophile to produce the photoresponsive 1,2-dithienylethene
      backbone. The reversible change in color when samples are irradiated with
      appropriate wavelengths of light occurs only after the Diels-Alder cycloaddition
      reaction takes place.

PMID- 15987183
TI  - Transformation of carbonates into sulfones at the benzylic position via palladium
      catalyzed benzylic substitution.
AB  - [reaction: see text] The nucleophilic substitution of benzylic carbonates with
      sodium arenesulfinates was catalyzed by the palladium complex generated in situ
      from [Pd(eta(3)-C(3)H(5))Cl](2) and DPEphos [bis(2
      diphenylphosphinophenyl)ether]. The catalytic reaction proceeded in DMSO at 80
      degrees C and gave a variety of benzylic sulfones in high yields.

PMID- 15987184
TI  - Phosphine-catalyzed synthesis of 6-substituted 2-pyrones: manifestation of E/Z
      isomerism in the zwitterionic intermediate.
AB  - [reaction: see text] We report a one-step phosphine-catalyzed annulation between
      aldehydes and ethyl allenoate to form 6-substituted 2-pyrones. The mechanistic
      rationale for this reaction requires explicit discussion of the E/Z-isomerism of
      the zwitterionic intermediate formed by the addition of a phosphine to the
      allenoate. Sterically demanding trialkylphosphines facilitate the shift of
      equilibrium toward the E-isomeric zwitterion and lead to the formation of 6
      substituted 2-pyrones. Various aromatic as well as aliphatic aldehydes undergo
      the transformation in moderate to excellent yield.

PMID- 15987185
TI  - Microwave-assisted intramolecular Suzuki-Miyaura reaction to macrocycle, a
      concise asymmetric total synthesis of biphenomycin B.
AB  - [reaction: see text] A concise and efficient total synthesis of biphenomycin B
      has been accomplished featuring a key microwave-assisted intramolecular Suzuki
      Miyaura reaction for formation of the 15-membered meta,meta-cyclophane 20.

PMID- 15987186
TI  - CO-trapping reaction under thermolysis of alkoxyamines: application to the
      synthesis of 3,4-cyclopenta-1-tetralones.
AB  - [reaction: see text] An efficient one-pot sequence comprising a PRE-mediated
      radical 5-exo-cyclization, a radical carbonylation, a nitroxide trapping
      reaction, and a subsequent acid-catalyzed Friedel-Craft-type acylation provides a
      new entry into 3,4-cyclopenta-1-tetralones. Eight examples are presented.

PMID- 15987187
TI  - A novel, expeditious synthesis of racemic camptothecin.
AB  - [reaction: see text] A novel and efficient synthesis of racemic camptothecin,
      starting from a readily accessible hydroxy pyridone, is presented. Key steps
      include a Claisen rearrangement of a functionalized allylic ether, a hindered
      Heck coupling, and a Friedlander condensation.

PMID- 15987188
TI  - Development of a stepwise [3 + 3] annelation to functionalized piperidines.
AB  - [reaction: see text] A stepwise formal [3 + 3] cycloaddition sequence via a
      Grignard addition-cyclization reaction leads to a much improved piperidine
      synthesis. This methodology provides improved flexibility in both the aziridine
      substrate and TMM equivalent.

PMID- 15987190
TI  - Gold(I)-phosphine catalyst for the highly chemoselective dehydrogenative
      silylation of alcohols.
AB  - [reaction: see text] A gold(I) complex of Xantphos AuCl(xantphos) catalyzes the
      dehydrogenative silylation of alcohols with high chemoselectivity and solvent
      tolerance. It is selective for the silylation of hydroxyl groups in the presence
      of alkenes, alkynes, alkyl halides (RCl, RBr), ketones, aldehydes, conjugated
      enones, esters, and carbamates.

PMID- 15987189
TI  - Biyouyanagin A, an anti-HIV agent from Hypericum chinense L. var. salicifolium.
AB  - [structure: see text] A structurally unique hydrophobic compound, biyouyanagin A,
      was isolated from the MeOH extract of the leaves of Hypericum chinense L. var.
      salicifolium. The structure of biyouyanagin A was elucidated on the basis of
      spectroscopic evidence. Biyouyanagin A showed a significant activity against HIV
      and inhibited cytokine production.

PMID- 15987191
TI  - Synthesis of a soluble ureido-naphthyridine oligomer that self-associates via
      eight contiguous hydrogen bonds.
AB  - [structure; see text] An iterative synthetic route to organic-soluble ureido
      naphthyridine oligomers has been developed. Use of this protocol allowed
      synthesis of a short ureido-naphthyridine oligomer, which presents a self
      complementary DDAADDAA hydrogen bonding array (D = hydrogen bond donor, A =
      hydrogen bond acceptor). Strong self-association via eight hydrogen bonds was
      observed in organic solution.

PMID- 15987192
TI  - Performing the synthesis of a complex molecule on sequentially linked columns:
      toward the development of a "synthesis machine".
AB  - [reaction: see text] We describe the diastereoselective synthesis of a
      pharmaceutically active drug candidate via a column-based system. This
      methodology is complementary to classical solid-phase synthesis; individual
      columns are packed with resin-bound reagents and then linked in sequence and/or
      in parallel. In contrast to the traditional solid-phase approach, substrates are
      introduced in the mobile phase where they build up chemical complexity by
      percolating through the linked columns, ultimately eluting as the desired
      product.

PMID- 15987193
TI  - Anion-mediated phase transfer of Zinc(II)-coordinated tyrosine derivatives.
AB  - [reaction: see text] Tyrosine-derived Zn(2+) coordination complexes and their
      fluorescent NBD conjugates are synthesized in a short, high-yielding procedure.
      The Zn(2+) complexes are highly water soluble, but in the presence of sodium
      laurate they readily transfer into an octanol layer. Furthermore, the NBD-labeled
      bis-Zn(2+) complex can partition into vesicle membranes containing anionic
      phospholipids.

PMID- 15987194
TI  - Salvinicins A and B, new neoclerodane diterpenes from Salvia divinorum.
AB  - [reaction: see text] Two new neoclerodane diterpenes, salvinicins A (4) and B
      (5), were isolated from the dried leaves of Salvia divinorum. The structures of
      these compounds were elucidated by spectroscopic techniques, including (1)H and
      (13)C NMR, NOESY, HMQC, and HMBC. The absolute stereochemistry of these compounds
      was assigned on the basis of single-crystal X-ray crystallographic analysis of
      salvinicin A (4) and a 3,4-dichlorobenzoate derivative of salvinorin B.

PMID- 15987195
TI  - Desymmetrization of glycerol derivatives with peptide-based acylation catalysts.
AB  - [reaction: see text] Nucleophile-loaded peptides have been evaluated as catalysts
      for the desymmetrization of glycerol derivatives through an enantioselective
      acylation process. Enantiomeric excesses of up to 97% have been obtained for the
      monoacylated products. A range of other substrates have been examined that shed
      light on the mechanistic basis of the desymmetrizations.

PMID- 15987197
TI  - Colorimetric and ratiometric fluorescent chemosensor with a large red-shift in
      emission: Cu(II)-only sensing by deprotonation of secondary amines as receptor
      conjugated to naphthalimide fluorophore.
AB  - [reaction: see text] A new fluorescent probe N-butyl-4,5-di[2
      (phenylamino)ethylamino]-1,8-naphthalimide 1 senses only Cu(II) among heavy and
      transition metal (HTM) ions by means of a colorimetric (primrose yellow to pink)
      method with a large red-shift in emission (green to red) attributed to the
      deprotonation of the secondary amines as a receptor conjugated to the
      naphthalimide fluorophore.

PMID- 15987196
TI  - Apoptolidins B and C: isolation, structure determination, and biological
      activity.
AB  - [reaction: see text] Apoptolidin (1) is a promising new therapeutic lead that
      exhibits remarkable selectivity against cancer cells relative to normal cells. We
      report the isolation, characterization, solution structure, stability, and
      biological activity of two new members of this family: apoptolidins B (2) and C
      (3). These new agents are found to have antiproliferative activity on par with or
      better than apoptolidin itself in an assay with H292 lung cancer cells.

PMID- 15987198
TI  - TEMPO-promoted Pauson-Khand reaction. Single-electron activation of cobalt
      carbonyl bonds?
AB  - [reaction: see text] The Pauson-Khand reaction is notably accelerated by TEMPO.
      According to DFT calculations, TEMPO could trigger a radical, low-energy pathway
      for the reaction by facilitating the decarbonylation of doublet complexes arising
      either from a CO/nitroxide exchange or from nitroxide addition to a CO ligand.

PMID- 15987199
TI  - Tagalsins I and J, two novel tetraterpenoids from the mangrove plant, Ceriops
      tagal.
AB  - [reaction: see text] Two novel bisdolabrane backbone tetraditerpenoids, tagalsins
      I (1) and J (2), were isolated from the mangrove plant, Ceriops tagal, and their
      structures were elucidated by means of extensive two-dimensional NMR (COSY, HMQC,
      HMBC, and NOESY), IR, and MS data analysis. The stereochemistry of 1 was further
      determined by single-crystal X-ray diffraction.

PMID- 15987200
TI  - 4,4'-Dimethyldinaphtho[a,d]cycloheptane, a naturally occurring polyaromatic
      derivative related to triterpenoids of the serratane series.
AB  - [reaction: see text] The polyaromatic hydrocarbon 4,4'
      dimethyldinaphtho[a,d]cycloheptane (1a) has been identified by NMR studies after
      isolation from an Oligocene sediment. The original symmetrical structure of 1a,
      which bears a central seven-membered ring, is closely related to higher plant
      triterpenoid precursor(s) of the serratane series and is believed to have been
      formed in the subsurface by a microbially mediated aromatization process.

PMID- 15987201
TI  - Total synthesis of (-)-(alpha)-kainic acid via a diastereoselective
      methylenecyclopropane ring expansion.
AB  - [reaction: see text] A concise and enantioselective synthesis of (-)-(alpha)
      kainic acid in 13 steps with an overall yield of 15% is reported. The pyrrolidine
      kainoid precursor with the required C2/C3 trans stereochemistry was prepared with
      excellent diastereoselectivity (>20:1) via a MgI(2)-mediated ring expansion of a
      tertiary methylenecyclopropyl amide. A selective hydroboration was then employed
      to set the remaining stereochemistry at the C4 position en route to (-)-(alpha)
      kainic acid.

PMID- 15987202
TI  - Ionic liquid as catalyst and reaction medium. The dramatic influence of a task
      specific ionic liquid, [bmIm]OH, in Michael addition of active methylene
      compounds to conjugated ketones, carboxylic esters, and nitriles.
AB  - [reaction: see text] A task-specific ionic liquid, [bmIm]OH, has been introduced
      as a catalyst and as a reaction medium in Michael addition. Very interestingly,
      although the addition to alpha,beta-unsaturated ketones proceeds in the usual
      way, giving the monoaddition products, this ionic liquid always drives the
      reaction of open-chain 1,3-dicarbonyl compounds with alpha,beta-unsaturated
      esters and nitriles toward bis-addition to produce exclusively bis-adducts in one
      stroke.

PMID- 15987203
TI  - Total synthesis of (+)-dactylolide.
AB  - [reaction: see text] The development of an approach leading to the total
      synthesis of dactylolide is described. The key features of this route include a
      catalytic asymmetric allylation, a diastereoselective pyran annulation, and a
      Horner-Wadsworth-Emmons macrocyclization.

PMID- 15987204
TI  - DABCO-catalyzed reaction of allenic esters and ketones with salicyl N
      tosylimines: synthesis of highly functionalized chromenes.
AB  - [reaction: see text] DABCO-catalyzed reactions of salicyl N-tosylimines with
      ethyl 2,3-butadienoate and penta-3,4-dien-2-one proceed smoothly at room
      temperature in dichloromethane to give the corresponding chromenes in good to
      excellent yields.

PMID- 15987206
TI  - Intramolecular cyclotrimerization of triynes catalyzed by N-heterocyclic carbene
      CoCl2/Zn or -FeCl3/Zn.
AB  - [reaction: see text] Triynes 1 could effectively be cyclotrimerized to annulated
      benzenes 2 by treatment with a catalytic amount of zinc powder, N-heterocyclic
      carbene, and CoCl(2) or FeCl(3).

PMID- 15987205
TI  - Tuning the regioselectivity of the Staudinger reaction for the facile synthesis
      of kanamycin and neomycin class antibiotics with N-1 modification.
AB  - [reaction: see text] A novel method for achieving the desired regioselective
      reduction of the N-1 azido group on a tetraazidoneamine has been developed that
      leads to the synthesis of both kanamycin and neomycin class antibiotics bearing N
      1 modification. Both classes of aminoglycosides are active against aminoglycoside
      resistant bacteria carrying APH(3')-I and AAC(6')/APH(2'').

PMID- 15987208
TI  - Expeditious approach to 5-aroyl-pyrrolidinones by a novel PIFA-mediated alkyne
      amidation reaction.
AB  - [reaction: see text] A novel metal-free approach to the alkyne amidation reaction
      is presented. The oxidation of properly substituted amides by the hypervalent
      iodine reagent PIFA provides the generation of a nitrenium ion that can react
      intramolecularly with a triple bond, leading to the construction of the title
      compounds.

PMID- 15987207
TI  - An effective and highly stereoselective Julia olefination of cyclopropyl carbinol
      mediated by CeCl3.7H2O/NaI.
AB  - [reaction: see text] An efficient and highly stereoselective synthesis of
      functionalized trisubstituted E-olefins from cyclopropyl carbinol derivatives via
      a Julia-type olefination mediated by an intriguing Lewis acidic system consisting
      of CeCl(3).7H(2)O and NaI in refluxing acetonitrile is reported. This facile
      olefination allows for the iterative incorporation of methylcyclopropyl ketone as
      a C(5) prenylation synthon in the synthesis of acyclic terpenoids, as
      demonstrated in the facile synthesis of plaunotol 6E-isomer 12, a biologically
      significant diterpene diol, and naturally occurring diterpene 17.

PMID- 15987210
TI  - Copper-catalyzed stereospecific N-allenylations of amides. Syntheses of optically
      enriched chiral allenamides.
AB  - [reaction: see text] Syntheses of chiral allenamides via a stereospecific
      amidation of optically enriched allenyl iodides using catalytic copper(I) salt
      and N,N'-dimethylethylene-diamine are described here.

PMID- 15987209
TI  - Highly regioselective, catalytic asymmetric reductive coupling of 1,3-enynes and
      ketones.
AB  - [reaction: see text] Highly regioselective, catalytic asymmetric reductive
      coupling reactions of 1,3-enynes and ketones have been achieved using catalytic
      amounts of Ni(cod)(2) and a P-chiral, monodentate ferrocenyl phosphine ligand.
      These couplings represent the first examples of catalytic, intermolecular
      reductive coupling of alkynes and ketones, enantioselective or otherwise, and
      afford synthetically useful 1,3-dienes possessing a quaternary carbinol
      stereogenic center in up to 70% ee.

PMID- 15987211
TI  - Enynylation of 2-iodo-4-(phenylchalcogenyl)-1-butenes via intramolecular
      chelation: approach to the synthesis of conjugated dienynes or trienynes.
AB  - [reaction: see text] 2-Iodo-4-(phenylchalcogenyl)-1-butenes 3 and 4, which are
      derived from methylenecyclopropanes 1, can be enynylated with alkynes catalyzed
      by Pd(OAc)(2) to give conjugated dienynes 5 and 6 in the absence of any phosphine
      ligand and copper salt, and trienyne 9a can be obtained by oxidation of compound
      5a. A plausible reaction mechanism has been proposed.

PMID- 15987212
TI  - Synthesis of the fully functionalized core structure of the antibiotic
      abyssomicin C.
AB  - [reaction: see text] The fully functionalized core structure 23 of abyssomicin C
      (6) containing an oxabicyclooctane ring and a tetronate was prepared via a Diels
      Alder approach. After hydroxylation of lactone 10 to the alpha-hydroxylactone 12,
      lactone opening led to the hydroxy ester 16. A directed epoxidation furnished the
      desired syn-epoxide 20. Acetylation of the tertiary hydroxyl group, followed by
      intramolecular Claisen condensation, gave directly the core structure 23.

PMID- 15987213
TI  - Inter- and intramolecular radical couplings of ene-ynes or halo-alkenes promoted
      by an InCl3/MeONa/Ph2SiH2 system.
AB  - [reaction: see text] An effective generation of indium hydride (HInCl(2)) under
      nonacidic conditions is achieved by transmetalation between Ph(2)SiH(2) and
      InCl(2)OMe. The presented system achieves the titled coupling reactions in a
      radical manner. In particular, the nonacidic character enables the applications
      to acid-sensitive inter- and intramolecular ene-yne couplings.

PMID- 15987214
TI  - Lipase-catalyzed glucose fatty acid ester synthesis in ionic liquids.
AB  - [reaction: see text] Glucose fatty acid ester synthesis with poly(ethylene
      glycol)-modified Candida antarctica lipase B (CAL-B) was performed in pure 1
      butyl-3-methyl imidazolium tetrafluoroborate [BMIM][BF(4)] (30% conversion) and
      in pure 1-butyl-3-methyl imidazolium hexafluorophosphate [BMIM][PF(6)] (35%
      conversion). In a solvent system composed of ionic liquid and 40% t-BuOH
      conversions up to 90% and isolated yields of up to 89% were achieved using fatty
      acid vinyl esters as acyl donors and commercial CAL-B.

PMID- 15987215
TI  - (+)-Sorangicin A synthetic studies. Construction of the C(1-15) and C(16-29)
      subtargets.
AB  - [structure: see text] Effective stereocontrolled syntheses of subtargets (-)-2
      and (-)-4, comprising respectively the C(16-29) and C(1-15) tetrahydropyran and
      dihydropyran moieties of the potent antibiotic (+)-sorangicin A (1), have been
      achieved. The cornerstone for the synthesis of (-)-2 involved an aldol tactic
      exploiting 1,4-induction, followed in turn by an acid-mediated
      cyclization/ketalization and hydrosilane reduction promoted by TMSOTf, while
      construction of (-)-4 entailed a stereoselective conjugate addition/alpha
      oxygenation sequence.

PMID- 15987216
TI  - Stereoselective intramolecular 1,3 C-H insertion in Rh(II) carbene reactions.
AB  - [reaction: see text] 1,3 C-H insertion has been found to be a predominant
      reaction pathway in the Rh(II)-mediated reaction of beta-tosyl alpha-diazo
      carbonyl compounds.

PMID- 15987217
TI  - Unusual cyclopropanation of 9-bromocamphor derivatives: a novel formal C(1)-C(7)
      bond cleavage of camphor.
AB  - [reaction: see text] An unusual cyclopropanation of 9-bromocamphor derivatives 1
      to a 7-spiro-cyclopropyl camphor derivative 3 was effected by the action of
      potassium tert-butoxide (or sodium hydride) in warm DMSO. The exo-hydroxy group
      and a non-hydrogen endo-substituent at C(2) have proven to be essential
      structural elements, and the solvent DMSO has proven to be the sole effective
      reaction medium. Tricyclic compound 3 undergoes a facile tandem Wagner-Meerwein
      rearrangement-cyclopropyl ring-opening under mild acidic conditions, leading to
      norbornenyl derivative 12 and subsequent Meinwald rearrangement of bicyclic
      epoxide 13 to a formal C(1)-C(7) bond cleavage product 14.

PMID- 15987218
TI  - The polyol domain of amphidinol 3. A stereoselective synthesis of the entire C(1)
      C(30) sector.
AB  - [structure: see text] The richly oxygenated C(1)-C(30) polyol segment of
      amphidinol 3 has been synthesized in protected form. Incorporated in this long
      chain are 10 of the 25 stereogenic centers housed in the target. The asymmetric
      pathway that has been developed is based on the efficient union of three
      independently prepared subunits.

PMID- 15987219
TI  - Total synthesis of quinolizidine alkaloid (-)-217A. Application of
      iminoacetonitrile cycloadditions in organic synthesis.
AB  - [reaction: see text] An intramolecular iminoacetonitrile [4 + 2] cycloaddition
      functions as the key step in an efficient total synthesis of the quinolizidine
      alkaloid (-)-217A.

PMID- 15987220
TI  - Enantioselective synthesis of axially chiral biaryls through rhodium-catalyzed
      complete intermolecular cross-cyclotrimerization of internal alkynes.
AB  - [reaction: see text] We have developed a cationic rhodium(I)/H8-BINAP complex
      catalyzed complete intermolecular cross-cyclotrimerization of internal alkynes
      with dialkyl acetylenedicarboxylates. This reaction was successfully applied to
      enantioselective synthesis of axially chiral biaryls utilizing internal alkynes
      bearing ortho-substituted phenyl and acetoxymethyl in each terminal position. The
      axial chirality is constructed at the formation of benzene rings with high
      enantioselectivity (up to 96% ee).

PMID- 15987221
TI  - Phosphine oxides as preligands in ruthenium-catalyzed arylations via C-H bond
      functionalization using aryl chlorides.
AB  - [reaction: see text] The use of air-stable, electron-rich phosphine oxides as
      preligands allows for unprecedented general ruthenium-catalyzed arylation
      reactions of pyridines and imines through C-H-bond activation using aryl
      chlorides. The catalytic system derived from a sterically hindered adamantyl
      substituted phosphine oxide proves highly efficient and tolerates a number of
      important functional groups.

PMID- 15987222
TI  - Remarkable tris(trimethylsilyl)silyl group for diastereoselective [2 + 2]
      cyclizations.
AB  - [reaction: see text] Diastereoselective [2 + 2] cyclizations of aldehyde- and
      ketone-derived silyl enol ethers with acrylates is described. The use of the
      tris(trimethylsilyl)silyl group allows for unprecedented reactivity, yields, and
      selectivity for these cyclizations. The presence of silicon-silicon bonds proved
      to be important for this transformation, where typical silyl groups (TBS and
      TIPS) failed to give any desired product. The bulky bis(2,6-diphenylphenoxide)
      aluminum triflimide catalyst was essential for high diastereoselectivity.

PMID- 15987223
TI  - Catalytic Synthesis of gamma-Lactams via direct annulations of enals and N
      sulfonylimines.
AB  - [reaction: see text] Cinnamaldehydes and N-sulfonylimines undergo direct
      annulations to cis-disubstituted gamma-lactams via the intermediacy of
      catalytically generated homoenolates. Critical to the success of this process was
      overcoming inhibition of the N-heterocyclic carbene catalyst by the electrophilic
      imines. The overall process proceeds with good yields and diastereoselectivites
      and requires no stoichiometric reagents or additives.

PMID- 15987224
TI  - Price differentiation and transparency in the global pharmaceutical marketplace.
AB  - Pharmaceutical manufacturers have increased the availability of their products
      and sometimes increased their own financial returns by charging lower prices
      outside of the US and by discounting to lower-income patients in the US. Examples
      include discounted HIV-AIDS drugs in developing countries and pharmaceutical
      manufacturers' discount cards in the US. Representatives of some international
      organisations argue that the price reductions are insufficient to make the
      medications widely available to lower-income patients. The WHO advocates both
      differential pricing and price transparency. While its efforts are well meaning,
      this paper identifies six concerns about its methods of comparing the price of a
      given molecule across manufacturers and across countries. More significantly, the
      WHO efforts to increase transparency are likely to lead to less price
      differentiation and less access to innovative pharmaceuticals. An important
      reason why manufacturers are reluctant to charge lower prices in lower-income
      countries is that they fear that such low prices will undermine the prices they
      charge to higher-income consumers. International organisations should not
      facilitate transparency but should dissuade governments from making price
      comparisons and basing their prices on those of lower-income countries.
      Furthermore, they should endeavour to keep low-priced and free drugs in the hands
      of the low-income consumers for which they were intended.

PMID- 15987225
TI  - Evaluating health-related quality-of-life studies in paediatric populations: some
      conceptual, methodological and developmental considerations and recent
      applications.
AB  - Although numerous paediatric-based health-related quality-of-life (HR-QOL)
      instruments are currently in use, there still remain conceptual, methodological
      and developmental issues to address. This paper provides an up-to-date critical
      review of the HR-QOL literature in paediatric medicine. Our analysis indicates
      that there is no consensus on how HR-QOL and overall QOL should be defined and
      measured in children. It is recommended that future studies focus on
      operationalising and distinguishing these constructs from each other and from
      traditional health-status measures. A clear empirical basis for generating
      instrument items and for prioritising specific domains must be described.
      Researchers should consider using the data gathered during their first interviews
      as a springboard from which to test their ideas of HR-QOL and QOL, reformulate
      concepts and subsequently retest their notions before developing instruments.
      Related to methodological challenges, consistency and agreement are still used
      interchangeably when comparing child and parent reports of children's HR-QOL. The
      Pearson correlation is a measure of co-variation in scores, and not a measure of
      agreement. We recommend that researchers focus on determining agreement as
      opposed to consistency. Few, if any, attempts have been made to account for the
      possibility that a response shift may have occurred in the evaluation of HR-QOL.
      Most studies have compared HR-QOL scores of children with illness with their
      healthy peers. As such, there is a dearth of knowledge regarding the normative
      process of adaptation within the context of illness. It is recommended that
      researchers focus on gathering data using a relative standard of comparison. We
      further recommend that researchers interpret HR-QOL data in line with their
      intended purpose. Regarding developmental consideration, particular attention
      ought to be paid to developing instruments that consider children's emerging
      sense of self, cognitive capacity and emotional awareness. Instruments that
      include items that are age appropriate are more likely to maximise reliability
      and validity of reports. The results of many HR-QOL instruments are applied in
      pharmacotherapeutic and pharmacoeconomic assessments. However, there has been
      relative infrequent application of economically valid HR-QOL tools (utility
      scales) and the use of HR-QOL scales as outcome measures in paediatric drug
      trials. As such, few cost-utility analyses have been performed to inform
      paediatric decision making. In addition, many of the concerns in the development
      of HR-QOL instruments should also be applied to the utility scales such that they
      reflect adequately children's preferences for health states.

PMID- 15987226
TI  - The state of patient-reported outcomes in atrial fibrillation : a review of
      current measures.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting
      approximately 2.2 million people in the US. The presentation of AF ranges from
      asymptomatic to severely symptomatic. When symptomatic, AF has been shown to have
      an adverse impact on health-related quality of life (HR-QOL) and to result in
      increased healthcare costs. The objective of this analysis was to review the
      current AF literature on patient-reported outcomes (PROs) in order to evaluate
      the impact of AF on PROs and the applicability of current PRO measures in
      assessing AF outcomes.HR-QOL and symptoms were the most frequently assessed PROs;
      however, the sensitivity of the majority of the questionnaires for detecting
      subtle change is not known. For highly symptomatic patients, interventional
      procedures reduce symptoms and improve HR-QOL; however, this is a small cohort of
      patients with AF. For the most part, PROs are equivalent between pharmacological
      treatments or are not known for the large percentage of patients treated
      pharmacologically with antiarrhythmic or rate-controlling drugs.PRO assessment in
      AF patients is an area that needs continued development. AF-specific PRO measures
      are needed to assess the full range of patient symptoms and treatment outcomes.
      The impact of paroxysmal AF versus permanent AF is not well delineated, and sex
      and nationality differences are not known. In addition, the impact of AF on daily
      activities and HR-QOL is not clearly described.

PMID- 15987227
TI  - Introducing economic evaluation as a policy tool in Korea: will decision makers
      get quality information? : a critical review of published Korean economic
      evaluations.
AB  - Interest in the use of economic evaluations in Korea as an aid for healthcare
      decision makers has been growing rapidly since the financial crisis of the Korean
      National Health Insurance fund and the separation in 2000 of the roles of
      prescribing and dispensing drugs. The Korean Health Insurance Review Agency
      (HIRA) is considering making it mandatory for pharmaceutical companies to submit
      the results of an economic evaluation when demanding reimbursement of new
      pharmaceuticals. The usefulness of the results of economic evaluations depends
      highly on the quality of the studies. The purpose of this paper, therefore, is to
      provide a critical review of economic evaluations of healthcare technologies
      published in the Korean context. Our results show that many studies did not meet
      international standards. Study designs were suboptimal, study perspectives and
      types were often stated incompletely, time periods were often too short, and
      outcome measures were often less than ideal. In addition, some articles did not
      distinguish between measurement and valuation of resource use. Capital, overhead
      and productivity costs were often omitted. Only half of the studies performed
      sensitivity analyses. In order to further rationalise resource allocation in the
      Korean healthcare sector, the quality of the information provided through
      economic evaluations needs to improve. Developing clear guidelines and educating
      and training researchers in performing economic evaluations is necessary.

PMID- 15987228
TI  - Economic assessment of adjustable maintenance treatment with
      budesonide/formoterol in a single inhaler versus fixed treatment in asthma.
AB  - OBJECTIVES: To compare the costs and effectiveness of adjustable maintenance
      dosing with budesonide/formoterol in a single inhaler versus fixed dosing in
      adults with asthma. METHODS: In this prospective, randomised, open-label,
      parallel-group, multicentre trial conducted in Germany, patients with asthma
      received budesonide/formoterol 160 microg/4.5 microg in a single inhaler
      (Symbicort Turbuhaler with two inhalations twice daily for a 4-week run-in
      period. Patients were then randomised to either adjustable maintenance dosing
      (one inhalation twice daily, stepping up to four inhalations twice daily for 1
      week if asthma worsened; n=1679) or fixed dosing (two inhalations twice daily;
      n=1618) for 12 weeks. The primary efficacy variable was the change in health
      related quality of life (HR-QOL), measured using the Asthma Quality of Life
      Questionnaire (standardised) during the randomised treatment period. Resource
      utilisation data were collected in parallel and combined with German unit costs
      to estimate direct and indirect costs (year 2001 values). RESULTS: Both treatment
      regimens were equally effective in maintaining HR-QOL and asthma control during
      the randomised treatment period. However, overall, patients in the adjustable
      maintenance dosing group took fewer daily inhalations of budesonide/formoterol
      than those in the fixed-dosing group (mean: 2.63 vs 3.82 inhalations; p<0.001).
      Adjustable maintenance dosing was associated with significantly lower asthma
      related direct costs compared with fixed dosing (mean: 221 euro vs 292 euro;
      p<0.001). This pattern was maintained when patients were stratified into those
      with peak expiratory flow (PEF) of 60% to <80% predicted normal and those with
      PEF of>/=80% predicted normal and when total costs were considered. CONCLUSION:
      Adjustable maintenance dosing with budesonide/formoterol in a single inhaler
      maintained HR-QOL in adult patients with asthma at a significantly lower cost
      than fixed dosing.

PMID- 15987231
TI  - Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of
      osteoarthritis and rheumatoid arthritis patients in the UK.

PMID- 15987229
TI  - Costs and medical care consequences associated with the diagnosis of peripheral
      arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is increasingly recognised as an
      indicator of disseminated atherothrombosis, but its impact on use of healthcare
      resources is not well understood. OBJECTIVE: To provide a quantitative
      description of the resource utilisation and costs incurred following PAD.
      METHODS: Hospitalisations, physician visits and the corresponding direct medical
      costs were examined in 16,440 patients with a diagnosis of PAD (1985--1995) in
      Saskatchewan, Canada, and compared with 15,590 reference patients with a
      diagnosis of myocardial infarction (MI) [1990--1995]. Medical history and patient
      characteristics were available retrospectively to January 1980 and follow-up to
      December 2000. Rates and timing of all-cause and cardiovascular hospitalisations
      and physician visits within discrete periods in the 10 years following PAD
      diagnosis, and 5 years following MI, were evaluated, as were lengths of stay and
      predictors of hospitalisation. RESULTS: Average follow-up was 5.9 years among
      patients with PAD and 3.6 years for MI. Half (55%) of patients with PAD were male
      versus 64% of reference patients. The mean ages were 67.3 and 66.9 years,
      respectively. Patients with PAD were hospitalised most frequently soon after
      diagnosis, with rates subsequently decreasing to 0.14 per month. These rates were
      similar in the reference group except for the period immediately following MI.
      The average 5-year cost post-diagnosis (2002 Can dollars) per patient was 41,968
      Can dollars vs 48,578 Can dollars for the reference population. CONCLUSIONS: A
      diagnosis of PAD not only imposes a severe burden on patients and their families,
      but it also significantly increases the use of healthcare resources and the
      associated costs. By the end of year 1, this burden is comparable with a
      diagnosis of MI.

PMID- 15987232
TI  - Role of antimicrobial agents in the management of exacerbations of COPD.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a
      common occurrence and characterize the natural history of the disease. Over the
      past decade, new knowledge has substantially enhanced our understanding of the
      pathogenesis, outcome and natural history of AECOPD. The exacerbations not only
      greatly reduce the quality of life of these patients, but also result in
      hospitalization, respiratory failure, and death. The exacerbations are the major
      cost drivers in consumption of healthcare resources by COPD patients. Although
      bacterial infections are the most common etiologic agents, the role of viruses in
      COPD exacerbations is being increasingly recognized. The efficacy of
      antimicrobial therapy in acute exacerbations has established a causative role for
      bacterial infections. Recent molecular typing of sputum isolates further supports
      the role of bacteria in AECOPD. Isolation of a new strain of Haemophilus
      influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was associated
      with a considerable risk of an exacerbation. Lower airway bacterial colonization
      in stable patients with COPD instigates airway inflammation, which leads to a
      protracted self-perpetuating vicious circle of progressive lung damage and
      disease progression. A significant proportion of patients treated for COPD
      exacerbation demonstrate incomplete recovery, and frequent exacerbations
      contribute to decline in lung function. The predictors of poor outcome include
      advanced age, significant impairment of lung function, poor performance status,
      comorbid conditions and history of previous frequent exacerbations requiring
      antibacterials or systemic corticosteroids. These high-risk patients, who are
      likely to harbor organisms resistant to commonly used antimicrobials, should be
      identified and treated with antimicrobials with a low potential for failure. An
      aggressive management approach in complicated exacerbations may reduce costs by
      reducing healthcare utilization and hospitalization.

PMID- 15987233
TI  - As-needed inhaled beta2-adrenoceptor agonists in moderate-to-severe asthma:
      current recommendations.
AB  - Intermediate-acting inhaled beta2-agonists (e.g. albuterol [salbutamol]), once
      recommended for round-the-clock bronchodilation, are now recommended to be used
      exclusively as-needed. Guidelines advise that asthma should be controlled with
      anti-inflammatory therapeutic strategies so that the as-needed requirement for
      inhaled beta2-agonists should be infrequent; ideally less than several times per
      week, up to once a day for exercise, and none at night. These recommendations are
      based upon the recognition that asthma is primarily an inflammatory condition and
      that the major thrust of therapy should be anti-inflammatory, including
      environmental control and administration of inhaled corticosteroids (ICS),
      leukotriene-receptor antagonists, and possibly oral theophylline and inhaled
      cromones; the cromones include cromolyn sodium (sodium cromogylcate) and
      nedocromil. While this is the primary rationale behind the as-needed infrequent
      prescription of the inhaled beta2-agonist paradigm, there are a number of
      detrimental effects that can be seen with regularly scheduled (or frequent as
      needed) use of inhaled beta2-agonists. These include tolerance to the
      bronchodilator and particularly the bronchoprotective effects, increased airway
      responsiveness to allergen, worsened asthma control, and, probably most
      importantly, over-reliance on an excellent symptom reliever leading to
      undertreatment. Any or all of these could be responsible for the demonstrated
      dose-response relationship between inhaled beta2-agonist overuse and death from
      asthma. Several controlled clinical trials, which have included many patients
      with at least moderately severe asthma, have failed to demonstrate any obvious
      advantage to the regular scheduled use of inhaled beta2-agonists compared with as
      needed inhaled beta2-agonists. On the other hand, despite no obvious advantage,
      regular use of albuterol 1000-1200 microg/day appears to be well tolerated and
      reasonably safe. When asthma is treated using an as-needed, infrequent inhaled
      beta2-agonist, the requirements for beta2-agonists become a useful marker of
      whether or not the asthma is adequately controlled. When inhaled beta2-agonists
      are required inordinately frequently (i.e. when asthma is not adequately
      controlled), after ensuring compliance with ICS, the most common strategy is to
      add one of the long-acting inhaled beta2-agonists twice daily. On the basis of
      the available evidence, the as-needed intermediate-acting inhaled beta2-agonist
      therapeutic strategy appears appropriate for patients with moderate-to-severe
      asthma.

PMID- 15987234
TI  - The role of oxidative stress in the pathogenesis of COPD: implications for
      therapy.
AB  - Chronic inflammation and oxidative stress are important features in the
      pathogenesis of COPD. The increased oxidative stress in patients with COPD is the
      result of an increased burden of inhaled oxidants, as well as increased amounts
      of reactive oxygen species (ROS) generated by various inflammatory, immune and
      epithelial cells of the airways. Oxidative stress has important implications on
      several events of lung physiology and for the pathogenesis of COPD. These include
      oxidative inactivation of antiproteases and surfactants, mucus hypersecretion,
      membrane lipid peroxidation, mitochondrial respiration, alveolar epithelial
      injury, remodeling of extracellular matrix, and apoptosis. An increased level of
      ROS produced in the airways is reflected by increased markers of oxidative stress
      in the airspaces, sputum, breath, lungs, and blood in patients with COPD. The
      biomarkers of oxidative stress such as H2O2, F2-isoprostanes, malondialdehyde and
      4-hydroxy-2-nonenal have been successfully measured in breath condensate. ROS and
      aldehydes play a key role in enhancing the inflammation through the activation of
      mitogen-activated protein kinases and redox-sensitive transcription factors such
      as nuclear factor kappa B and activator protein-1. Oxidative stress also alters
      nuclear histone acetylation and deacetylation leading to increased gene
      expression of pro-inflammatory mediators in the lung. Oxidative stress may play a
      role in the poor clinical efficacy of corticosteroids in the treatment of COPD.
      Since a variety of oxidants, free radicals, and aldehydes are implicated in the
      pathogenesis of COPD it is likely that a combination of antioxidants may be
      effective in the treatment of COPD. Antioxidant compounds may also be of
      therapeutic value in monitoring oxidative biomarkers indicating disease
      progression. Various approaches to enhance the lung antioxidant screen and the
      clinical effectiveness of antioxidant compounds in the treatment of COPD are
      discussed.

PMID- 15987235
TI  - Lung volume reduction surgery: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Observational studies have suggested that lung volume reduction
      surgery (LVRS) is superior to optimal medical therapy for selected subsets of
      patients with advanced emphysema. Randomized clinical trials (RCTs) with the
      exception of the National Emphysema Treatment Trial (NETT), failed to enroll a
      sufficient number of patients to provide clinicians and patients with convincing
      outcome data on the usefulness of LVRS. It was postulated that a meta-analysis of
      these RCTs (3-12 months' follow up) may provide more compelling information on
      the value of LVRS in patients with emphysema. METHODS: A comprehensive search of
      the MEDLINE database between January 1994 and January 2004 for RCTs on LVRS was
      performed. RESULTS: From a total of eight RCTs on record, six studies (306
      patients) with 3- to 12-month follow up were deemed suitable for meta-analysis.
      Key baseline features of these RCT populations included heterogeneous emphysema,
      comparable inclusion/exclusion criteria and, in retrospect, low walking capacity
      as measured by the 6-minute walk distance (6MWD). This profile closely resembles
      NETT's 'predominantly upper lobe--low exercise tolerance emphysema' cohort. The
      LVRS arm of the meta-analysis population showed better results than the medical
      cohort in terms of pulmonary function (FEV(1) p < 0.0001, FVC p < 0.0001,
      residual volume p < 0.0001, total lung capacity p = 0.004), gas exchange
      (arterial partial pressure of oxygen p < 0.0001) and exercise capacity (6MWD p =
      0.0002). Although information on quality-of-life measures was not sufficiently
      uniform to qualify for meta-analysis, a survey of available data revealed better
      results in the surgical than in the medical arms of each RCT. Mortality 6-12
      months after random assignment to treatment was similar in the two study arms,
      suggesting that the operative mortality from LVRS was offset, within months, by
      deaths in the medical arm. CONCLUSIONS: This meta-analysis showed that a selected
      subset of patients with advanced, heterogeneous emphysema and low exercise
      tolerance (6MWD) experienced better outcomes from LVRS than from medical therapy.

PMID- 15987236
TI  - Lung volume reduction surgery: a breath of fresh air.

PMID- 15987237
TI  - Ipratropium bromide HFA.
AB  - Ipratropium bromide is a nonselective antagonist of the muscarinic receptors
      located on airway smooth muscle, and is delivered via a metered-dose inhaler
      (MDI). Because of the requirement to phase out chlorofluorocarbon (CFC)-propelled
      MDIs, the ipratropium bromide inhalation aerosol MDI has been redesigned with a
      hydrofluoroalkane as the propellant (ipratropium bromide HFA). Ipratropium
      bromide HFA has recently been approved in the US for the maintenance treatment of
      bronchospasm associated with COPD. Ipratropium bromide HFA 42 microg four times
      daily (one dose [42 microg] is delivered via two puffs of the inhaler)
      demonstrated comparable efficacy to that of ipratropium bromide CFC 42 microg
      four times daily, as measured by spirometric testing, in a large, randomized,
      double-blind, placebo-controlled, 12-week trial in patients with stable COPD.
      Similarly, four-times-daily ipratropium bromide HFA 42 microg and ipratropium
      bromide CFC 42 microg provided a comparable degree of bronchodilation in patients
      with stable COPD during a 1-year, open-label study primarily designed to assess
      safety. In both studies, the tolerability profiles of ipratropium bromide HFA and
      ipratropium bromide CFC were comparable. The most common adverse events were
      related to respiratory system disorders. During the 1-year study, dry mouth was
      reported by 1.3% and 0.7% of patients in the ipratropium bromide HFA or
      ipratropium bromide CFC groups.

PMID- 15987244
TI  - FoxO6 transcriptional activity is regulated by Thr26 and Ser184, independent of
      nucleo-cytoplasmic shuttling.
AB  - Forkhead members of the 'O' class (FoxO) are transcription factors crucial for
      the regulation of metabolism, cell cycle, cell death and cell survival. FoxO
      factors are regulated by insulin-mediated activation of PI3K (phosphoinositide 3
      kinase)-PKB (protein kinase B) signalling. Activation of PI3K-PKB signalling
      results in the phosphorylation of FoxO factors on three conserved phosphorylation
      motifs, which are essential for the translocation of FoxO factors from the
      nucleus to the cytosol. FoxO6, however, remains mostly nuclear due to the fact
      that its shuttling ability is dramatically impaired. FoxO1, FoxO3 and FoxO4 all
      contain an N- and C-terminal PKB motif and a motif located in the forkhead
      domain. FoxO6 lacks the conserved C-terminal PKB motif, which is the cause of the
      shuttling impairment. Since FoxO6 can be considered constitutively nuclear, we
      investigated whether it is also a constitutively active transcription factor. Our
      results show that FoxO6 transcriptional activity is inhibited by growth factors,
      independent of shuttling, indicating that it is not constitutively active. The
      PKB site in the forkhead domain (Ser184) regulated the DNA binding
      characteristics and the N-terminal PKB site acted as a growth factor sensor. In
      summary, FoxO6 is not a constitutively active transcription factor and can be
      regulated by growth factors in a Thr26- and Ser184-dependent manner, independent
      of shuttling to the cytosol.

PMID- 15987245
TI  - Proceedings and abstracts from the 7th Workshop on the Neurobiology of Epilepsy
      (WONOEP VII). Ericeira, Portugal, October 7-11, 2003.

PMID- 15987246
TI  - Differential GABA(A) subunit expression following status epilepticus in seizure
      prone and seizure-resistant rats: a putative mechanism for refractory drug
      response.
AB  - PURPOSE: Two rat strains were selectively bred to be prone (Fast) or resistant
      (Slow) to amygdala kindling. The first objective of this experiment was to
      determine whether that selection was specific to kindling or was sensitive more
      broadly to another seizure induction agent, kainic acid (KA). Second, we
      investigated whether these strains exhibit distinct molecular responses to KA
      with respect to GABA(A) receptor subunit expression. METHODS: Development of
      status epilepticus (SE) was profiled in Fast and Slow rats injected with 20 mg/kg
      KA (i.p.). Two hours post-SE onset, rats received a sedative dose of sodium
      pentobarbital. Behavioral profiles included latency to SE, number of wet dog
      shakes (WDS), and number and duration of stage 3-5 generalized seizures. Rats
      were killed 24 h post-SE, and alpha(1) and alpha(4) mRNA levels were compared in
      the hippocampus and amygdala using QPCR. RESULTS: Slow rats exhibited a much
      greater latency to SE onset (p < 0.01) and many more WDS (p < 0.01) than Fast
      rats. During SE, Fast rats spent more time in and exhibited more repeated bouts
      of generalized stage 3-5 seizures (p < 0.01) than Slow rats. Constitutive levels
      of alpha1 and alpha4 were not different between the strains in either structure
      and equivalent reductions in alpha4 were evident 24 h post-SE. However, while
      Fast rats showed KA-induced reductions in alpha1 in both structures, Slow rats
      showed significant elevations. CONCLUSIONS: Genetic selection for temporal lobe
      excitability, manifested as differential amygdala kindling rates, is paralleled
      by vulnerability to KA-induced SE. Further, these strains exhibited at least one
      opposing molecular response to SE, namely alpha1 expression. This finding may
      offer a putative mechanism through which seemingly similar epilepsies can be
      intractable in some patients but treatable in others.

PMID- 15987247
TI  - Developmental program of epileptogenesis in the brain of EL mice.
AB  - PURPOSE: We recently observed inducible nitric oxide synthetase (iNOS) expression
      and decreased Cu, Zn-superoxide dismutase (Cu, Zn-SOD) activities in the
      hippocampus of epileptic mutant EL mice at the age of 30 weeks. In addition, the
      immediate early gene (IEG) c-fos is unusually expressed in the interictal period,
      suggesting activation of protein cascades associated with the epileptogenesis.
      Furthermore, DNA fragmentation has been detected preferentially in the
      hippocampus CA1 and the parietal cortex of EL mouse brain. It remains to be seen,
      however, how these abnormalities are related to the DNA fragmentation, and
      whether neuronal cell loss is involved. The present study was designed to address
      these issues. METHODS: NOS isoenzymes, pro- (Bax) and antiapoptotic factors (Bcl
      2, Bcl-XL), and neurotrophic factors (brain-derived neurotrophic factor, BDNF;
      neurotrophin-3, NT-3; fibroblast growth factor-2, FGF-2) were determined by
      immunoblotting in the EL mouse brain at various developmental stages. Hematoxylin
      eosin staining was applied to the formalin-fixed brains to examine the cell loss
      in the tissue. IEG expression in the interictal period was analyzed by in situ
      hybridization by using the 35S x-ray emulsion method. RESULTS: nNOS was the major
      component of NOS in the hippocampus of either EL or control DDY mice. In EL mice,
      however, iNOS was detectable at the age of 10 weeks, at which the animals usually
      experience the first seizures. eNOS, which appears in DDY brain, could scarcely
      be identified. Even in the interictal period, EL mice expressed c-fos
      continuously, preferentially in the parietal cortex and hippocampal CA1. In DDY
      mice, very low steady-state levels of Bcl-2 and Bax remained constant throughout
      development. In EL mice, these Bcl-2 and Bax levels were increased even before
      experiencing frequent seizures. BDNF in EL mice markedly increased temporarily
      during ictogenesis and epileptogenesis in their early periods. Unexpectedly, no
      cell loss was found in the hippocampus. CONCLUSIONS: DNA fragmentation without
      cell loss found in EL mouse brains appears to result from initial activation and
      later inactivation of the apoptotic process. Neurotrophic factors may play a role
      in the ictogenesis and the epileptogenesis during the early development. These
      gene expressions closely related to the periods critical for ictogenesis and
      epileptogenesis may be of particular importance in the development of
      antiepileptic drugs (AEDs) with novel mechanisms.

PMID- 15987248
TI  - The subiculum: a potential site of ictogenesis in human temporal lobe epilepsy.
AB  - PURPOSE: This study determines synaptic and intrinsic alterations of subicular
      pyramidal cells that are associated with activity recorded in patients suffering
      from temporal lobe epilepsy. METHODS: Electroencephalograms with sphenoidal
      electrodes were correlated with in vitro single cell recordings of subicular
      pyramidal cells from the corresponding resected epileptic tissue. We determined
      alterations of synaptic and intrinsic properties of subicular pyramidal cells
      that accompany spontaneous rhythmic activity in human sclerotic and nonsclerotic
      epileptic tissue. RESULTS: We found that in sclerotic, but also in nonsclerotic
      hippocampal tissue, the subiculum showed cellular and synaptic changes that were
      associated with spontaneous rhythmic activity correlated to the occurrence and
      frequency of interictal discharges recorded in the electroencephalograms of the
      corresponding patients. CONCLUSIONS: Even though Ammon's horn sclerosis (AHS) in
      resected hippocampi from patients suffering from temporal lobe epilepsy has
      important prognostic implications for freedom from seizures postoperatively, we
      report here that both synaptic and intrinsic alterations enhance seizure
      susceptibility of the subiculum also in the absence of classical AHS.

PMID- 15987249
TI  - Disruption of cortical development as a consequence of repetitive pilocarpine
      induced status epilepticus in rats.
AB  - PURPOSE: The aim of the present study was to observe possible cortical
      abnormalities after repetitive pilocarpine-induced status epilepticus (SE) in
      rats during development. METHODS: Wistar rats received intraperitoneal injection
      of pilocarpine hydrochloride 2% (380 mg/kg) at P7, P8, and P9. All experimental
      rats displayed SE after pilocarpine injections. Rats were killed at P10 and P35,
      and immunocytochemistry procedures were performed on 50-microm vibratome
      sections, by using antibodies against nonphosphorylated neurofilament (SMI-311),
      parvalbumin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase
      (GAD-65). Selected sections were used for the TUNEL method and double-labeling
      experiments, with different mixtures of the same markers. RESULTS: The major
      findings of the present work were (a) altered intracortical circuitry
      development; (b) anticipation of PV immunoreactivity in neocortical interneurons;
      (c) increased GAD-65 immunoreactivity; and (d) reduced neocortical apoptotic
      process. CONCLUSIONS: From these results, we suggest that previously healthy
      brain, without genetic abnormalities, might develop an "acquired" disruption of
      cortical development whose evolution reproduces some characteristics of the
      childhood epilepsies associated with cognitive impairment.

PMID- 15987250
TI  - Changes of cortical interhemispheric responses after status epilepticus in
      immature rats.
AB  - PURPOSE: To study cortical excitability after status epilepticus induced in two
      age groups of immature rats. METHODS: Lithium-pilocarpine status epilepticus was
      elicited in 12- (SE12) or 25-day-old (SE25) rats. Control siblings received
      saline instead of pilocarpine. Interhemispheric responses were elicited by
      stimulation of sensorimotor region of cerebral cortex 3, 6, 9, 13, or 26 days
      after status. Single biphasic pulses with intensities from 0.2 to 4 mA were used
      for stimulation; eight responses were always averaged. Amplitude of the first
      positive and negative waves (i.e., monosynaptic transcallosal responses) was
      measured and used for construction of input-output (I/O) curves. FluoroJade B was
      used to visualize degenerating neurons 24 h after status in both age groups.
      RESULTS: No significant changes were found at short intervals, but only a
      tendency to lower amplitudes 3 days after status in SE12 group. Marked changes
      appeared 26 days after status. The younger group exhibited lower amplitudes than
      did control rats, whereas SE25 animals generated responses with higher amplitude
      than did controls (i.e., the I/O curve was steeper. FluoroJade B-positive neurons
      were scarce in SE12 rats, whereas a substantial number of positive neurons was
      found in SE25 animals. The positive neurons exhibited characteristics of
      interneurons, and their distribution in cortical layers differed in the two
      groups. CONCLUSIONS: Status epilepticus resulted in neuronal death in both SE12
      and SE25 animals. Changes in transcallosal evoked potentials were opposite in the
      two age groups. Augmented amplitude of responses in SE25 rats may indicate an
      increased cortical excitability.

PMID- 15987251
TI  - Outcome of status epilepticus in immature rats varies according to the
      paraldehyde treatment.
AB  - PURPOSE: To test effects of paraldehyde on behavioral outcome of status
      epilepticus (SE) in developing rats. METHODS: Motor SE was induced by LiCl
      pilocarpine in rats on postnatal (P) day 12 or 25. Two hours after SE onset,
      animals were injected with a single dose of paraldehyde (0.07 and 0.3 ml/kg in
      the P12 group and 0.3 and 0.6 ml/kg in the P25 group). Effects on seizure
      severity and mortality were evaluated. Growth of animals and their motor
      abilities were monitored until the adulthood. Three months after SE, cognitive
      abilities were tested by using the Morris water maze. RESULTS: Both tested doses
      of paraldehyde equally affected motor seizures. Convulsions continued until the
      paraldehyde administration, but then they quickly subsided in all groups. During
      the subsequent 24 h, occasional clonic seizures occurred in P25 animals treated
      with the lower dose of paraldehyde. Only hyperactivity and/or automatisms were
      observed in the other experimental groups. Mortality was not affected by the
      dosage of paraldehyde. The higher dosage of paraldehyde improved recovery after
      SE in both age groups. No difference was found in motor abilities between
      controls and SE animals, except shortening of time spent on the rod in the
      rotarod test in the P12 group. In P25 rats, treatment with a higher dosage of
      paraldehyde improved learning abilities compared with the lower dosage. In the
      P12 group, animals treated with the lower dosage exhibited slightly impaired
      learning compared with controls and animals receiving the higher dosage.
      CONCLUSIONS: Paraldehyde injected 2 h after SE onset modulates long-term outcome
      in immature rats in a dose-related manner.

PMID- 15987252
TI  - Programmed neuronal necrosis and status epilepticus.
AB  - We examined the mechanism of neuronal necrosis induced by hypoxia in dentate
      gyrus cultures or by status epilepticus (SE) in adult mice. Our observations
      showed that hypoxic necrosis can be an active process starting with early
      mitochondrial swelling and loss of the mitochondrial membrane potential, followed
      by cytochrome c release and caspase-9-dependent activation of caspase-3. This
      sequence of events (or program) was independent of protein synthesis and may be
      induced by energy failure and/or calcium overloading of mitochondria. We called
      this form of necrosis "programmed necrosis." After SE in adult mice, CA1 and CA3
      pyramidal neurons displayed a necrotic morphology, associated with caspase-3
      immunoreactivity and with double-stranded DNA breaks, suggesting that "programmed
      necrosis" may be involved in SE-induced neuronal loss.

PMID- 15987253
TI  - Reduced serotonin and 3-hydroxyanthranilic acid levels in serum of cystatin B
      deficient mice, a model system for progressive myoclonus epilepsy.
AB  - PURPOSE: To evaluate the levels of tryptophan and its metabolites along serotonin
      (5-HT) and kynurenine (KYN) pathways in serum of progressive myoclonus epilepsy
      (EPM1) patients and cystatin B (CSTB)-deficient mice, a model system for EPM1.
      METHODS: Tryptophan and its metabolites along serotonin (5-HT) and KYN pathways
      were determined in serum of EPM1 patients and CSTB-deficient mice by reverse
      phase high-pressure liquid chromatography (HPLC) with electrochemical detection.
      RESULTS: Reduced levels of 5-HT and KYN intermediate metabolite 3
      hydroxyanthranilic acid were found in serum of CSTB-deficient mice. A similar
      trend was found in EPM1 patients. Although tryptophan concentration was reduced
      in serum of EPM1 patients, no such decrease was observed in CSTB-deficient mice.
      CONCLUSIONS: The present study demonstrates that tryptophan metabolism along 5-HT
      and KYN pathways are disrupted in EPM1. Further studies are needed to elucidate
      the role of KYN pathway in pathogenesis of EPM1.

PMID- 15987254
TI  - Alterations in seizure susceptibility and in seizure-induced plasticity after
      pharmacologic and genetic manipulation of the fibroblast growth factor-2 system.
AB  - PURPOSE: The adult brain undergoes activity-dependent plastic modifications
      during pathologic processes that are reminiscent of those observed during
      development. For example, seizures induce neuronal loss, neurogenesis, axonal and
      dendritic sprouting, gliosis, and circuit remodeling. Neurotrophic factors and
      fibroblast growth factor-2 (FGF-2), in particular, are well-known mediators in
      each of these cellular events. The aim of this minireview is to summarize and
      discuss the data supporting the idea that FGF-2 may be involved in seizure
      generation and in their sequelae. METHODS: We used epilepsy models of kainate and
      kindling, with FGF-2 knockout mice and FGF-2 overexpressing mice. RESULTS:
      Seizures increase FGF-2 mRNA and protein levels in specific brain areas and
      upregulate the expression of its receptor FGFR-1. Short-term intrahippocampal
      injection of FGF-2 cause seizures, whereas long-term i.c.v. infusion of low-dose
      FGF-2 does not affect kainate seizures but promotes behavioral recovery and
      reduces hippocampal damage. Kainate seizure severity is not altered in FGF-2
      knockout mice, but is increased in FGF-2 overexpressing mice. CONCLUSIONS: FGF-2
      is implicated in seizure susceptibility and in seizure-induced plasticity.

PMID- 15987255
TI  - Analysis of seizure onset on the basis of wideband EEG recordings.
AB  - Seventy-five seizure onsets recorded with depth electrodes in the frequency band
      from 0.1 to 70 Hz were analyzed in 19 patients with intractable temporal lobe
      epilepsy. It was shown that 89% of low-voltage fast-type seizures contained an
      initial slow wave, whereas hypersynchronous-type seizures did not show an initial
      slow wave. Voltage depth profile analysis illustrated that the peak amplitude of
      the initial slow-wave onset was in white matter, whereas the peak amplitude of
      hypersynchronous onset was in deep temporal areas (hippocampus, entorhinal
      cortex, or amygdala). The difference in voltage depth profiles suggests that
      these two types of seizure onsets have different mechanisms of generation. The
      absence of phase reversal of the initial slow wave in white matter or at the
      border of deep temporal areas indicates a possible nonneuronal mechanism of
      generation.

PMID- 15987256
TI  - The role of extracellular potassium in the epileptogenic transformation of
      recurrent GABAergic inhibition.
AB  - PURPOSE: Epileptiform burst-firing can occur in hippocampal area CA1 where
      recurrent excitation is relatively weak and recurrent inhibition strong. Recent
      observations suggest that recurrent inhibition can transform into recurrent
      excitation because of collapse of the chloride gradient. Here we assess the role
      of potassium in this epileptogenic transformation. METHODS: Extracellular field
      potential recordings, combined with either intracellular recordings from
      pyramidal neurons or extracellular potassium concentration recordings, were made
      in vitro from isolated CA1 minislices cut from the rat hippocampus and in vivo
      from area CA1 in urethane-anesthetized rats. Burst responses were evoked by 5-Hz
      alveus stimulation. RESULTS: The 5-Hz alveus stimulation in vitro caused a
      transient period of burst responses that was associated with a transient increase
      in synaptic input in stratum oriens and a transient shift of the reversal
      potential of the synaptic potential. These changes were related to the transient
      increase in extracellular potassium concentration in stratum oriens. Observations
      in vivo confirmed the relation between bursting and extracellular potassium
      concentration in stratum oriens. CONCLUSIONS: Use-dependent increase of
      extracellular potassium concentration in stratum oriens facilitates the collapse
      of the chloride gradient in the basal dendrites and transforms gamma-aminobutyric
      acid (GABA)ergic inhibition into GABAergic excitation, giving rise to burst
      firing. Improvement of intracellular chloride homeostasis or extracellular
      potassium homeostasis could reduce epileptogenicity.

PMID- 15987257
TI  - Physiological changes in chronic epileptic rats are prominent in superficial
      layers of the medial entorhinal area.
AB  - PURPOSE: We investigated whether the functional network properties of the medial
      entorhinal area (MEA) of the entorhinal cortex were altered in a rat model of
      chronic epilepsy that is characterized by extensive cell loss in MEA layer III.
      METHODS: Responses were evoked in the entorhinal cortex by electrical stimulation
      of the subiculum in anesthetized chronic epileptic rats, 2-4 months after status
      epilepticus, induced by systemic kainate (KA) injections. Laminar field
      potentials were measured using a 16-channel silicon probe that covered all six
      layers of the MEA; an estimate of the local transmembrane currents was made using
      current source density analysis. RESULTS: Double-pulse stimulation of the
      subiculum evoked responses in deep and superficial layers of the MEA in control
      and KA rats. A current sink in layer I and at the border of layer I and II that
      was induced by antidromic activation of MEA-II, was much more prominent in KA
      rats with extensive neuronal loss in MEA-III than in control rats or KA rats with
      minor MEA-III loss. Furthermore, KA rats that displayed MEA-III loss presented a
      series of oscillations induced by subicular stimulation in the beta/gamma
      frequency range (20-100 Hz), which were confined to superficial layers of MEA.
      These oscillations were never observed in control rats or KA rats with minor MEA
      III loss. CONCLUSIONS: These results indicate that the observed alterations in
      the superficial MEA responses to subiculum stimulation and the occurrence of
      beta/gamma-oscillations are related phenomena, which are a consequence of altered
      and impaired inhibition within these MEA layers in chronic epileptic rats.

PMID- 15987258
TI  - Are cytomegalic neurons and balloon cells generators of epileptic activity in
      pediatric cortical dysplasia?
AB  - PURPOSE: Severe cortical dysplasia (CD) is characterized by the presence of
      cytomegalic neurons and balloon cells. These aberrant cells could participate in
      the generation of epileptic activity. The aim of this study was to
      morphologically and electrophysiologically characterize cells in pediatric CD
      tissue. METHODS: We used infrared video-microscopy to visualize normal and
      abnormal-appearing cells. To characterize electrophysiological properties, we
      used whole-cell patch clamp recordings in tissue slices obtained from 42 cases of
      pediatric CD (ages 0.2-14 years). The pipette contained biocytin for
      determination of morphological features. RESULTS: Approximately 25% of recorded
      cells displayed morphologic differences compared with normal-appearing pyramidal
      neurons, and were divided as follows: immature, misoriented, dysmorphic,
      cytomegalic, and balloon cells. Immature cells displayed electrophysiological
      membrane properties typical of developing neurons. Misoriented pyramidal neurons
      and pyramidal neurons with dysmorphic processes displayed properties similar to
      normal-appearing pyramidal neurons. In contrast, cytomegalic neurons and balloon
      cells displayed abnormal membrane properties. Balloon cells had a very high input
      resistance and lacked voltage-gated Na+ and Ca2+ currents. Cytomegalic neurons
      had a very high membrane capacitance, very low input resistance, and showed signs
      of hyperexcitability, as exemplified by the occurrence of repetitive, slowly
      inactivating Ca2+ spikes when depolarized. CONCLUSIONS: We suggest that
      cytomegalic neurons but not balloon cells have the potential to be epileptic
      generators, although probably not instigators, in severe CD tissue.

PMID- 15987259
TI  - Changes in cytochrome oxidase in the piriform cortex after status epilepticus in
      adult rats.
AB  - PURPOSE: The piriform cortex is involved in genesis and propagation of temporal
      lobe seizures. Degenerating neurons demonstrated by FluoroJade B staining are
      visible early after status epilepticus (SE) as well as after longer intervals.
      Furthermore, the piriform cortex is activated during an early phase of
      experimental temporal seizures, as described by magnetic resonance imaging (MRI)
      studies. It indicates that the early activity of the piriform cortex should be
      accompanied by increased adenosine triphosphate (ATP) production. Cytochrome
      oxidase activity in the brain may be used as an endogenous metabolic marker for
      neurons. The present research studied activity of the cytochrome oxidase
      separately in the rostral and caudal parts of the piriform cortex after lithium
      chloride-pilocarpine-induced SE in adult rats. METHODS: SE was induced by a
      single dose of pilocarpine (40 mg/kg) in LiCl-pretreated adult Wistar rats.
      Cytochrome oxidase activity was mapped by optical density on sections stained
      with histochemistry separately in the rostral and caudal parts of the piriform
      cortex. RESULTS: Optical density of the rostral part of the piriform cortex
      remained nearly unchanged at both 1 week (0.284 +/- 0.009 in SE group vs. 0.297
      +/- 0.005 in controls) and 3 months (0.318 +/- 0.007 in SE group vs. 0.333 +/-
      0.004 in controls) after SE intervals. The caudal part of the piriform cortex
      showed a decrease of optical density in both groups at 1 week (0.265 +/- 0.007 in
      SE group vs. 0.285 +/- 0.009 in controls) and 3 months after SE (0.292 +/- 0.006
      in SE animals vs. 0.310 +/- 0.003 in controls), respectively. Nissl-stained
      sections demonstrated a marked neuronal loss and gliosis and/or necrotic cavities
      through the caudal piriform cortex 1 week after SE. CONCLUSIONS: Our results
      demonstrated that damage of the piriform cortex is not homogeneous and thus that
      its parts are differently involved in epileptic activity.

PMID- 15987260
TI  - The acute and chronic effect of vagus nerve stimulation in genetic absence
      epilepsy rats from Strasbourg (GAERS).
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of acute and chronic
      vagus nerve stimulation (VNS) in genetic absence epilepsy rats from Strasbourg
      (GAERS). This is a validated model for absence epilepsy, characterized by
      frequent spontaneous absences concomitant with spike and wave discharges (SWD) on
      the EEG. Although absences are a benign form of seizures, it is conceptually
      important to investigate the efficacy of VNS in a controlled study by using this
      chronic epilepsy model. METHODS: Both control and stimulated GAERS were implanted
      with five epidural EEG electrodes and a stimulation electrode around the left
      vagus nerve. In the first experiment, VNS was given when SWD occurred in the EEG;
      this was repeated the next day. A randomized crossover design (n = 8) was used.
      In the chronic experiment, GAERS underwent EEG monitoring during a first baseline
      week. During the second week, the treated group (n = 18) received VNS; controls
      (n = 13), on the other hand, only underwent EEG recordings. RESULTS: On day 1 of
      the acute VNS experiment, the mean duration of the SWD when VNS was applied was
      higher than in baseline conditions (p < 0.05). However, on day 2, there was no
      difference in mean duration of the SWD. In the chronic VNS experiment, no
      statistically significant differences were found between control and stimulated
      GAERS. CONCLUSIONS: Acute VNS applied shortly after the onset of SWD prolonged
      the mean duration of SWD in GAERS at least during the first day of VNS. Chronic
      stimulation hardly affected SWD in GAERS.

PMID- 15987261
TI  - Long-term deep brain stimulation for refractory temporal lobe epilepsy.

PMID- 15987262
TI  - Detection of increased local excitatory circuits in the hippocampus during
      epileptogenesis using focal flash photolysis of caged glutamate.
AB  - PURPOSE: Local synaptic circuits, particularly recurrent excitation, are
      hypothesized to contribute to the generation and synchronization of epileptiform
      activity. The present study tested whether local excitatory circuits in the
      hippocampus are increased in an animal model of temporal lobe epilepsy, and thus
      may contribute to epileptic seizures. METHODS: Rats were given hourly injections
      of kainic acid to induce status epilepticus, which led to chronic epilepsy with
      spontaneous recurrent seizures. Whole-cell recording was performed in hippocampal
      slices, and focal flash photolysis of caged glutamate was used to detect local
      excitatory circuits. RESULTS: In the dentate gyrus of rats with kainate-induced
      epilepsy and mossy fiber sprouting, focal stimulations with caged glutamate at
      many different sites in the granule cell layer consistently evoked repetitive
      excitatory postsynaptic currents (EPSCs) in normal medium and prolonged bursts of
      action potentials in bicuculline; these responses were not observed in similarly
      treated slices from control rats. In CA1, focal flash photolysis of caged
      glutamate in stratum pyramidale revealed significantly more excitatory
      connections between CA1 pyramidal cells in rats with kainate-induced epilepsy
      than saline-treated control animals. CONCLUSION: Focal flash photolysis of caged
      glutamate revealed that new local excitatory circuits are formed in both the
      dentate gyrus and CA1 area of rats with kainate-induced epilepsy, which supports
      the hypothesis that the progressive formation of new local excitatory circuits
      occurs in many locations during epileptogenesis.

PMID- 15987263
TI  - GABA receptors as broadcasters of sexually differentiating signals in the brain.
AB  - Epileptic seizures are more common in males than in females. One of the areas
      that has recently been implicated in the higher susceptibility of males to
      seizures is the substantia nigra reticulata (SNR). Several studies support the
      existence of phenotypic differences between male and female infantile SNR
      neurons, and particularly in several aspects of the GABAergic system, including
      its ability to control seizures. We have recently found that at postnatal day 14
      17 (PN14-17) rats, which are equivalent to infants, activation of GABA(A)
      receptors has different physiological effects in male and female SNR neurons.
      This is likely due to the differences in the expression of the neuronal-specific
      potassium-chloride co-transporter KCC2, which regulates the intracellular
      chloride concentration. In male PN14-17 SNR neurons, GABA(A)-receptor activation
      with muscimol causes depolarization and increments in intracellular calcium
      concentration and the expression of calcium regulated genes, such as KCC2.
      Blockade of L-type voltage-sensitive calcium channels (L-VSCC) by nifedipine
      decreases KCC2 mRNA expression. However, in PN14-17 females, muscimol
      hyperpolarizes the SNR neurons, does not increase intracellular calcium, and
      decreases KCC2 mRNA expression. In PN15 females, nifedipine has no effect on KCC2
      mRNA expression in the SNR. This sexually dimorphic function of GABA(A) receptors
      also creates divergent patterns of estradiol signaling. In male PN15 rats,
      estradiol decreases KCC2 mRNA expression in SNR neurons. Pretreatment with the
      GABA(A)-receptor antagonist bicuculline or with nifedipine, prevents the
      appearance of estradiol-mediated downregulation of KCC2 mRNA expression. In
      contrast, in PN15 females, estradiol does not influence KCC2 expression. These
      findings show that, in infantile rats, drugs or conditions that modulate the
      activity of GABA(A) receptors or L-VSCCs have different effects on the
      differentiation of the SNR. As a result, they have the potency of causing long
      term changes in the function of the SNR in the control of seizures, movement, and
      the susceptibility to and course of epilepsy and movement disorders.

PMID- 15987264
TI  - Inflammatory response and glia activation in developing rat hippocampus after
      status epilepticus.
AB  - PURPOSE: We investigated the activation of microglia and astrocytes, induction of
      cytokines, and hippocampal neuronal damage, 4 and 24 h after kainic acid-induced
      status epilepticus (SE) in postnatal day (PN) 9, 15, and 21 rats. METHODS: Limbic
      seizures were induced by systemic injection of kainic acid. Glia activation and
      neuronal cell loss were studied by using immunocytochemistry and Western blot.
      Cytokine expression was analyzed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) followed by Southern blot quantification. RESULTS: After SE
      onset, hippocampal glia activation, cytokine expression, and neuronal damage are
      all age-dependent phenomena. In the hippocampus, neuronal injury occurs only when
      cytokines are induced in glia, and cytokine synthesis precedes the appearance of
      degenerating neurons. Neuronal injury is more pronounced when interleukin-6 (IL
      6) and tumor necrosis factor-alpha (TNF-alpha) are produced in addition to IL
      1beta. CONCLUSIONS: This study shows that cytokine induction in rat brain after
      sustained seizures is age dependent, and it is associated with the appearance of
      cell injury.

PMID- 15987265
TI  - Plastic changes and disease-modifying effects of scopolamine in the pilocarpine
      model of epilepsy in rats.
AB  - PURPOSE: We describe the use of a clinically relevant pharmacological
      intervention that alters the clinical history of status epilepticus (SE)-induced
      spontaneous recurrent seizures (SRS) in the pilocarpine model and the possible
      plastic changes underlying such an effect. METHODS: Two hours after pilocarpine
      induced SE (320-350 mg/kg, i.p.), rats received scopolamine 1-2 mg/kg i.p. or
      saline, every 6 h for 3 days. After that, osmotic minipumps were implanted for
      continuous delivery of scopolamine or saline for an additional 14 days. Animals
      were video-monitored for 12 h/week during the following 3-month period for the
      occurrence of SRS and, thereafter, were perfused, processed, and coronal brain
      sections were stained for acetylcholinesterase (AChE) and for the presence of
      supragranular mossy fibers (Timm). RESULTS: Treatment with scopolamine led to
      significantly fewer SRS. Staining for AChE in the dentate gyrus was significantly
      more intense in naive animals. The scopolamine group had the least intense AChE
      staining of all groups. However, regression analysis of the AChE staining for
      this group did not correlate with the presence or absence of SRS, or the latency
      or frequency of SRS. Supragranular mossy fiber sprouting developed in all animals
      experiencing pilocarpine-induced SE, irrespective of whether or not they were
      treated with scopolamine. CONCLUSIONS: Pilocarpine-induced SE in the presence of
      scopolamine might produce animals that, despite mossy fiber sprouting, were not
      seen to exhibit spontaneous seizures. In addition, our data suggest that the
      encountered changes in the AChE staining in the dentate gyrus that followed
      treatment with scopolamine do not help to explain its disease-modifying effects.

PMID- 15987266
TI  - Growth-associated protein 43 expression in hippocampal molecular layer of chronic
      epileptic rats treated with cycloheximide.
AB  - PURPOSE: GAP43 has been thought to be linked with mossy fiber sprouting (MFS) in
      various experimental models of epilepsy. To investigate how GAP43 expression
      (GAP43-ir) correlates with MFS, we assessed the intensity (densitometry) and
      extension (width) of GAP43-ir in the inner molecular layer of the dentate gyrus
      (IML) of rats subject to status epilepticus induced by pilocarpine (Pilo),
      previously injected or not with cycloheximide (CHX), which has been shown to
      inhibit MFS. METHODS: CHX was injected before the Pilo injection in adult Wistar
      rats. The Pilo group was injected with the same drugs, except for CHX. Animals
      were killed between 30 and 60 days later, and brain sections were processed for
      GAP43 immunohistochemistry. RESULTS: Densitometry showed no significant
      difference regarding GAP43-ir in the IML between Pilo, CHX+Pilo, and control
      groups. However, the results of the width of the GAP43-ir band in the IML showed
      that CHX+Pilo and control animals had a significantly larger band (p = 0.03) as
      compared with that in the Pilo group. CONCLUSIONS: Our current finding that
      animals in the CHX+Pilo group have a GAP43-ir band in the IML, similar to that of
      controls, reinforces prior data on the blockade of MFS in these animals. The
      change in GAP43-ir present in Pilo-treated animals was a thinning of the band to
      a very narrow layer just above the granule cell layer that is likely to be
      associated with the loss of hilar cell projections that express GAP-43.

PMID- 15987267
TI  - Modification of epileptiform discharges in neocortical neurons following
      glutamate uptake inhibition.
AB  - Sodium-dependent high-affinity glutamate transporters regulate synaptic glutamate
      levels to maintain low ambient levels of glutamate and prevent excitotoxicity.
      Most studies using pharmacological inhibition of glutamate transport to examine
      the involvement of glutamate transporters in regulating synaptic activity have
      examined small synaptic currents. Using in vitro brain slices, we investigated
      the effects of uptake inhibition on two types of epileptiform activity,
      bicuculline-induced paroxysmal activity, and epileptiform responses in the freeze
      lesion epilepsy model. In layer II/III pyramidal cells of the prefrontal cortex,
      inhibiting uptake with low concentrations of DL-threo-ss-benzyloxyaspartic acid
      (TBOA) (20 or 30 microM) prolonged bicuculline-induced epileptiform activity. At
      higher concentrations, TBOA (150 or 300 microM) caused a transient enhancement of
      epileptiform discharges that was followed by a decrease. In the freeze-lesion
      model, inhibiting uptake also increased the amplitude and response area of evoked
      activity. The prolongation of epileptiform activity exhibited by the inhibition
      of glutamate uptake (TBOA 20 or 30 microM) is attributed to an increase in the
      level of glutamate extracellularly during uptake blockade, resulting in sustained
      activation of glutamate receptors. The decrease in epileptiform activity at
      higher TBOA concentration could be due to glutamate receptor desensitization or
      loss of excitability due to a depolarization block. The present results suggest
      that decreases in glutamate uptake can be proconvulsant in the two models of
      epilepsy examined.

PMID- 15987268
TI  - Plasticity, synaptic strength, and epilepsy: what can we learn from
      ultrastructural data?
AB  - Central nervous system synapses have an intrinsic plastic capacity to adapt to
      new conditions with rapid changes in their structure. Such activity-dependent
      refinement occurs during development and learning, and shares features with
      diseases such as epilepsy. Quantitative ultrastructural studies based on serial
      sectioning and reconstructions have shown various structural changes associated
      with synaptic strength involving both dendritic spines and postsynaptic densities
      (PSDs) during long-term potentiation (LTP). In this review, we focus on
      experimental studies that have analyzed at the ultrastructural level the
      consequences of LTP in rodents, and plastic changes in the hippocampus of
      experimental models of epilepsy and human tissue obtained during surgeries for
      intractable temporal lobe epilepsy (TLE). Modifications in spine morphology,
      increases in the proportion of synapses with perforated PSDs, and formation of
      multiple spine boutons arising from the same dendrite are the possible sequence
      of events that accompany hippocampal LTP. Structural remodeling of mossy fiber
      synapses and formation of aberrant synaptic contacts in the dentate gyrus are
      common features in experimental models of epilepsy and in human TLE. Combined
      electrophysiological and ultrastructural studies in kindled rats and chronic
      epileptic animals have indicated the occurrence of seizure- and neuron loss
      induced changes in the hippocampal network. In these experiments, the synaptic
      contacts on granule cells are similar to those described for LTP. Such changes
      could be associated with enhancement of synaptic efficiency and may be important
      in epileptogenesis.

PMID- 15987269
TI  - GABA synapses and the rapid loss of inhibition to dentate gyrus granule cells
      after brief perforant-path stimulation.
AB  - PURPOSE: To study the pharmacologic and synaptic basis for the early loss of
      paired-pulse inhibition that occurs in the perforant-path stimulation model of
      status epilepticus. METHODS: Hippocampal slices were prepared from male Wistar
      rats. Test paired pulses (20- to 50-ms interstimulus interval) of the perforant
      path were used before and after an abbreviated period of perforant-path
      stimulation (1-5 min; 2-Hz continuous with 20 Hz of 10 s/min pulses) while either
      recording field potentials from the dentate gyrus granule cell layer or directly
      measuring whole-cell patch-clamp currents from granule cells. Paired-pulse field
      recordings also were obtained during perfusion of the gamma-aminobutyric acid
      (GABA)(A) antagonist bicuculline. RESULTS: Prolonged loss of paired-pulse
      inhibition occurs after brief (< 5 min) perforant-path stimulation in vitro
      (similar to results in vivo) with the paired-pulse population spike amplitude
      ratio (P2/P1) increasing from a baseline of 0.53 +/- 0.29 to 1.17 +/- 0.09 after
      perforant-path stimulation (p < 0.05). After perfusion with the GABA(A)
      antagonist, bicuculline, the P2/P1 ratio also increased from a baseline of 0.52
      +/- 0.16 to 1.15 +/- 0.26 (p < 0.05). After 1-2 min of perforant-path
      stimulation, a 22 +/- 6% (p < 0.05) decrease occurred in the P2/P1 amplitude
      ratio of paired-pulse evoked inhibitory postsynaptic currents. CONCLUSIONS:
      Similar to in vivo, loss of paired-pulse inhibition occurs with brief perforant
      path stimulation in vitro. GABA(A) antagonism causes a similar loss of paired
      pulse inhibition, and the effects of perforant-path stimulation on postsynaptic
      inhibitory currents also are consistent with the involvement of GABA(A) synaptic
      receptors. The findings suggest that loss of inhibition at GABA synapses may be
      an important early event in the initiation of status epilepticus.

PMID- 15987270
TI  - Behavioral and histopathological analysis of domoic Acid administration in
      marmosets.
AB  - PURPOSE: To induce status epilepticus (SE) followed by the subsequent onset of
      spontaneous recurrent seizures, thus characterizing a new model of temporal lobe
      epilepsy in a nonhuman primate. METHODS: Male and female marmosets (Callithrix
      jacchus) (n = 18), ages between 2 and 8 years, were injected with domoic acid
      (0.5-4 mg/kg, i.p.) or saline, and behaviorally assessed with regard to the
      presence of acutely induced seizures and for < or = 6 months for spontaneous
      seizures. Injection of doses ranging from 3.5 to 4 mg/kg either did not induce SE
      or resulted in fatal SE. Even a 5-min SE duration (SE blockade resulting from
      diazepam injection) proved lethal to marmosets within 1 h of domoate
      administration, regardless of intensive care and monitoring of the animals.
      Animals injected with doses ranging from 0.5 to 3 mg/kg that developed only a few
      minor convulsive signs were allowed a 6-month survival period for the assessment
      of spontaneous epileptic events. At the end of the experiment, 6-month period, or
      acute intoxication associated with SE induction, animals were deeply anesthetized
      and had their brains subjected to histologic processing for Nissl and delta-FosB.
      RESULTS: For the animals injected with domoate that did not develop SE (i.e.,
      those that survived), we could not detect any behavioral signs of spontaneous
      epileptic seizures in the 6-month observation period, and only minor indications
      of neuropathologic changes (i.e., neuronal death) over Nissl-stained sections, as
      well as some small changes in the staining for delta-FosB in a few of the
      animals. CONCLUSIONS: Systemic administration of domoic acid to marmosets is not
      effective for the generation of a model of chronic temporal lobe epilepsy.
      Administration of domoic acid at doses that do not lead to SE also did not lead
      to the development of temporal lobe epilepsy or clear-cut behavioral changes over
      a 6-month period.

PMID- 15987271
TI  - Autoantibodies and cell-mediated autoimmunity to NMDA-type GluRepsilon2 in
      patients with Rasmussen's encephalitis and chronic progressive epilepsia
      partialis continua.
AB  - PURPOSE: To evaluate antibody-mediated and cytotoxic T cell-mediated
      pathogenicity that has been implicated as the autoimmune pathophysiological
      mechanism in Rasmussen's encephalitis. METHODS: We examined autoantibodies
      against the N-methyl-d-aspartate glutamate receptor (NMDA-type GluR) epsilon2
      subunit and its epitopes in serum and CSF samples from 20 patients [five
      histologically proven (definitive) Rasmussen's encephalitis with epilepsia
      partialis continua (EPC), four definitive Rasmussen's encephalitis without EPC,
      and 11 clinical Rasmussen's encephalitis with EPC]. We examined 3H-thymidine
      uptake into lymphocytes after stimulation by GluRs. RESULTS: All nine definitive
      patients (five patients with EPC and four without EPC), and 10 of 11 clinical
      Rasmussen's encephalitis patients had the autoantibodies. In four patients, the
      autoantibodies were absent in early stage when epileptic seizures had already
      become frequent, and appeared subsequently. In two patients, the autoantibodies
      persisted in the serum after frontal lobe resection or functional
      hemispherectomy, although epileptic seizures were completely controlled.
      Autoantibodies to the C2 epitope predominated, while autoantibodies to the
      extracellular N epitope were rare. The mean 3H-thymidine uptake ratios
      (stimulation by GluRepsilon2-containing homogenates/stimulation by PHA) were
      significantly higher in definitive and clinical Rasmussen encephalitis patients
      than in controls. The mean 3H-thymidine uptake ratios (relative to PHA) were
      significantly higher for GluRepsilon2-containing homogenate than for control
      homogenate or GluRdelta2-containing homogenate. CONCLUSIONS: Autoantibodies
      against GluRepsilon2 may be one of the diagnostic markers for Rasmussen's
      encephalitis with and without EPC. Patients have activated T cells stimulated by
      GluRepsilon2 in peripheral blood circulation. We speculate that cellular
      autoimmunity and the subsequent humoral autoimmunity against GluRepsilon2 may
      contribute to the pathophysiological processes in Rasmussen's encephalitis.

PMID- 15987272
TI  - Long-term effect of convulsive behavior on the density of adenosine A1 and A 2A
      receptors in the rat cerebral cortex.
AB  - PURPOSE: Adenosine is a neuromodulator that has been proposed to act as an
      anticonvulsant mainly via inhibitory A1 receptors, but recent data show that
      genetic deletion of facilitatory A 2A receptors might also attenuate convulsions.
      Since both A1 and A 2A receptors are prone to down- and upregulation in different
      stressful situations, we investigated if convulsive behavior leads to a long-term
      change in A1 and A 2A receptor density in the rat cerebral cortex. METHODS: Stage
      4-5 convulsions (Racine's scale) were induced in adult Wistar rats either through
      amygdala stimulation (kindling) or by intraperitoneal injection of kainate (10
      mg/ml). Rats were killed after 4 weeks to evaluate adenosine A1 and A 2A receptor
      density in the cerebral cortex using both Western blot and membrane binding
      assays. RESULTS: The binding density of the A1 antagonist, 3H-DPCPX, decreased by
      40. +/- 4.4% and by 20.7 +/- 0.5% after kindling or kainate injection. Likewise,
      A1 receptor immunoreactivity in cortical membranes from kindled or kainate
      injected rats decreased by 19.1 +/- 3.3% and 12.7 +/- 5.7%, respectively. In
      contrast, the binding density of the A 2A receptor antagonist 3H-SCH 58261
      increased by 293 +/- 34% and by 159 +/- 32% in cortical membranes from kindled or
      kainate-injected rats, and A 2A receptor immunoreactivity also increased by 151
      +/- 12% and 79.6 +/- 7.0%. CONCLUSIONS: This indicates that after convulsive
      behavior there is a long-term decrease of A1 receptors accompanied by an
      increased density of A 2A receptors, suggesting that A 2A antagonists rather than
      A1 agonists may be more promising anticonvulsive drugs.

PMID- 15987273
TI  - Modulation of seizures and synaptic plasticity by adenosinergic receptors in an
      experimental model of temporal lobe epilepsy induced by pilocarpine in rats.
AB  - PURPOSE: Adenosine is a major negative neuromodulator of synaptic activity in the
      central nervous system and can exert anticonvulsant and neuroprotective effects
      in many experimental models of epilepsy. Extracellular adenosine can be formed by
      a membrane-anchored enzyme ecto-5'-nucleotidase. The purposes of this study were
      to characterize the role of adenosine receptors in modulating status epilepticus
      (SE) induced by pilocarpine and evaluate its neuroprotective action. Ecto-5'
      nucleotidase activity was studied during the different phases of pilocarpine
      induced epilepsy in rats. METHODS: Adult rats were pretreated with different
      adenosinergic agents to evaluate the latency and incidence of SE induced by
      pilocarpine in rats. The neuroprotective effect also was evaluated. RESULTS: A
      proconvulsant effect was observed with DPCPX and DMPX that reduced the latency of
      SE in almost all rats. Pretreatment with the MRS 1220 did not alter the incidence
      of SE but reduced the latency to develop SE. An anticonvulsant and
      neuroprotective effect was detected with R-PIA. Rats pretreated with R-PIA had a
      decreased number of apoptotic cells in the hippocampus, whereas pretreatment with
      DPCPX did not modify the hippocampal damage. An intensification of neuronal death
      was observed in the dentate gyrus and CA3 when rats were pretreated with DMPX.
      MRS-1220 did not modify the number of apoptotic cells in the hippocampus. An
      increase in the ecto-5 -nucleotidase staining was detected in the hippocampus
      during silent and chronic phases. CONCLUSIONS: The present data show that
      adenosine released during pilocarpine-induced SE via A1-receptor stimulation can
      exhibit neuroprotective and anticonvulsant roles. Similar effects could also be
      inferred with A2a and A3 adenosinergic agents, but further experiments are
      necessary to confirm their roles. Ecto-5 -nucleotidase activity during silent and
      chronic phases might have a role in blocking spontaneous seizures by production
      of inhibitory neuromodulator adenosine, besides taking part in the mechanism that
      controls sprouting.

PMID- 15987274
TI  - Functional properties of ES cell-derived neurons engrafted into the hippocampus
      of adult normal and chronically epileptic rats.
AB  - PURPOSE: Embryonic stem (ES) cell-based therapy strategies are thought to bear
      considerable promise in chronic neurologic disorders. Nonetheless, studies
      addressing the functional properties of ES cell-derived progeny after
      transplantation into the adult, pathologically modified CNS are scarce. METHODS:
      We therefore transplanted ES cell-derived neural precursors expressing enhanced
      green fluorescent protein only in neuronal progeny bilaterally into the
      hippocampi of pilocarpine-treated chronically epileptic and sham-control rats.
      Whole-cell patch-clamp recordings of identified ES cell-derived neurons (ESNs) in
      hippocampal slices were performed 13 to 34 days after transplantation. RESULTS:
      Most ESNs were found in clusters at the transplant site and did not migrate into
      host tissue. However, they gave rise to a dense network of processes extending
      over large distances into the host tissue. All ESNs possessed the ability to
      generate action potentials and expressed voltage-gated Na+ and K+ currents, as
      well as hyperpolarization-activated currents. Likewise, most ESNs received non-N
      methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)A receptor-mediated
      synaptic input. Both types of synapses displayed intact short-term plasticity. An
      unusual feature of the majority of ESNs was the occurrence of spontaneous
      pacemaking activity at frequencies approximately 3 Hertz. No obvious differences
      were found between the functional properties of ESNs in sham-control and in
      pilocarpine-treated rats. CONCLUSIONS: After transplantation into adult control
      and epileptic rats, ESNs displayed intrinsic and synaptic properties
      characteristic of neurons. Even though ESNs remained close to the transplant
      site, the formation of extensive networks of graft-derived processes may be
      useful for ES cell-based substance delivery.

PMID- 15987275
TI  - Central-type benzodiazepine receptors and epileptogenesis: basic mechanisms and
      clinical validity.
AB  - PURPOSE: Gamma-aminobutyric acid (GABA)-A/benzodiazepine receptors (BZRs) play an
      important inhibitory role in epileptogenesis. [123I]Iomazenil (123I-IMZ) is a
      specific ligand for central-type (or neuronal-type) BNRs and is available for
      single-photon emission computed tomography (SPECT) in brain disorders. We
      demonstrated alterations of central-type BZRs in human focal epilepsies and their
      experimental models. METHODS: We examined interictal 123I-IMZ SPECT in patients
      with mesial temporal lobe epilepsy (MTLE; n = 19) with hippocampal sclerosis and
      neocortical epilepsy with focal cortical dysplasia (NE-CD; n = 18), and compared
      those with magnetic resonance imaging (MRI) and 123I-IMP SPECT (for regional
      cerebral blood flow). We also investigated in vitro autoradiography with (123)I
      IMZ at various time courses in the intraamygdala kainate, amygdala kindling, and
      in-utero irradiation models. RESULTS: In MTLE patients, the epileptogenic
      hippocampus often showed decreases in both 123I-IMZ and 123I-IMP SPECT.
      Consistent with those, marked reduction of 125I-IMZ binding was observed in
      hippocampal CA1-3 regions of the kainate model, which clearly paralleled
      pyramidal neuronal loss. In contrast, 125I-IMZ binding was increased in the
      dentate gyrus at 1 month but returned to the normal level at 3-6 months, when
      frequent spontaneous seizures appeared. The amygdala-kindling model demonstrated
      similar increases in 125I-IMZ binding in the dentate gyrus without any changes in
      other brain regions. In NE-CD patients, the epileptogenic foci showed decreased
      123I-IMZ binding with relatively normal 123I-IMP SPECT. 125I-IMZ binding also was
      decreased in the cerebral cortex, hippocampus (areas CA1, 2, and 4), and
      caudate/putamen of the in-utero irradiation model. CONCLUSIONS: These results
      indicate that central-type BZRs neuroimaging is useful for detection of
      epileptogenic foci, but their alterations differ between epilepsy subtypes and
      time-courses.

PMID- 15987276
TI  - Proechimys guyannensis: an animal model of resistance to epilepsy.
AB  - PURPOSE: The potential interest of Proechimys guyannensis (PG), a spiny rat
      species living in the Amazonian region, as an animal model of anticonvulsant
      mechanisms, prompted the investigation of the susceptibility of this animal
      species to different epileptogenic treatments. METHODS: Adult male Wistar and PG
      animals were submitted to amygdala kindling, the pilocarpine model and the
      intrahippocampal kainic acid (KA) model. Electrographic, behavioral, and
      neuropathological changes were compared between Wistar and PG animals. RESULTS:
      PG animals demonstrated a striking resistance to reaching stage 5 of kindling. Of
      the 43 PG rats submitted to the kindling process, only three animals reached
      stage 5. In the pilocarpine and KA models, doses lower than those used in Wistar
      rats were able to induce status epilepticus (SE) in PG animals. Pilocarpine
      induced SE in PG had a shorter duration, rarely exceeding 2 h, in contrast to the
      8- to 12- h long SE in the Wistar rat. Of the 61 PG animals injected with
      pilocarpine, 48 presented with SE and only two presented with some spontaneous
      seizures after silent periods of 60 and 66 days. KA elicited self-sustained
      electrographic SE in PG animals, which lasted for 72 h. None of the surviving
      animals presented with spontaneous seizures in the long-term observation period
      (up to 120 days). CONCLUSIONS: These findings indicate that the PG animal may
      have natural endogenous anticonvulsant mechanisms and also may be an animal model
      that is resistant to epileptogenic treatments.

PMID- 15987282
TI  - Long-lasting follow-up favours a close relationship between progressive facial
      hemiatrophy and scleroderma en coup de sabre.

PMID- 15987283
TI  - Epidermal stem cells.
AB  - The identification of adult epidermal stem cells that are capable of self-renewal
      and can reconstitute not only the epidermis but also the cutaneous appendages
      opens new perspectives for the treatment of a variety of human skin disorders
      including severe burns, cutaneous cancers, alopecia and acne. However, the
      implementation and improvement of these novel treatment strategies require a
      better understanding of the biology of stem cells, in particular regarding their
      isolation and the maintenance of their unique characteristics in culture. In this
      review, we summarize the main features of epidermal stem cells and we present the
      most recent advances in our understanding of the development and maintenance of
      these cells. In addition, we discuss some of the challenges and the potential
      clinical applications of epidermal stem cell technology.

PMID- 15987284
TI  - Tacalcitol in the treatment of psoriasis vulgaris: the Spanish experience.
AB  - BACKGROUND: A group of vitamin D derivatives has revealed to be an efficient
      treatment for psoriasis. Different types of studies have been designed to confirm
      the efficacy of its use without relevant side-effects. OBJECTIVE: Evaluation of
      tolerability and efficacy of tacalcitol ointment in moderate psoriasis. DESIGN: A
      2-month multicentre prospective open-label observational study in patients with
      psoriasis treated with tacalcitol ointment. METHODS: A cohort of patients with
      psoriasis vulgaris seeking medical advice and being treated with tacalcitol based
      on the decision of their dermatologists was selected. A 2-month follow-up was
      performed to assess efficacy and tolerability of tacalcitol in an ointment
      formulation (4 microg/g) once daily. A psoriatic lesion was selected in each
      patient in order to assess clinical symptoms (erythema, desquamation and
      thickness) by means of five-point scale: 0 (none) to 4 (maximal severity).
      Percentages of involved skin, adverse effects, physicians' global assessments of
      efficacy and tolerability, and patients' global satisfaction scores were also
      evaluated after 15-30 days (first visit) and 2 months (second visit) of
      treatment. RESULTS: A total of 556 patients were included. Mean psoriasis
      duration was 10.1 years (range, 0-61 years). Follow-up data were available for
      493 patients in first follow-up visit and 449 in second (final) visit. Adverse
      events were uncommon (1.0% and 0.6% of patients in first and second follow-up
      visits, respectively). At first follow-up visit, mean decrease in selected
      lesions surface area (from a baseline value of 185.8 cm(2) per lesion) was 11.1
      cm(2) (95% CI, 1.6-20.6; P = 0.0213). After 2 months of treatment, mean scores
      for erythema, desquamation and thickness changed from 2.2 +/- 0.8 to 1.1 +/- 0.8
      (19% of patients with no erythema at final visit); from 2.4 +/- 0.8 to 0.6 +/-
      0.7 (55% of patients with no desquamation); and from 2.2 +/- 0.9 to 0.8 +/- 0.6
      (51% of patients with less thickness), respectively. Mean percentage of total
      body skin involvement was 14% (7.5% and 6.9% of anterior and posterior body
      surface, respectively). After 2 months of treatment, a 3.2% (95% CI, 2.7-3.8; P =
      0.0001) and 3.0% (95% CI, 2.4-3.6; P = 0.0001) decrease was observed in the
      percentage of involved anterior and posterior skin surface area, respectively.
      Efficacy and tolerability evaluation by investigators was very good or good in
      94% and 74% of patients, respectively; 78% of patients evaluated study treatment
      as satisfactory/very satisfactory. More than 80%, 50-80% and less than 50% of
      prescribed doses were used by 88%, 9.3% and 2.3% of patients, respectively.
      CONCLUSIONS: Tacalcitol was highly effective in the symptomatic treatment of
      moderate psoriasis. Compliance was very high, probably due to the easy and
      convenient application. Physicians' global assessments of tacalcitol were
      excellent, both for tolerability and efficacy. Excellent tolerability was
      confirmed by the low rate of adverse events. Our results in an everyday clinical
      setting show that tacalcitol is a useful therapy in patients with moderate
      psoriasis.

PMID- 15987285
TI  - Effect of psoriasis treatment on plasma concentrations of metalloproteinase-1 and
      tissue inhibitor of metalloproteinases-1.
AB  - AIM: The aim of this study was to evaluate the effect of psoriasis treatment on
      plasma concentrations of metalloproteinase-1 (MMP-1) and tissue inhibitor of
      metalloproteinases-1 (TIMP-1) with respect to disease severity. METHODS: MMP-1
      and TIMP-1 were measured using an enzyme immunoassay in plasma of 32 patients
      before and after topical treatment. Data were analysed with respect to baseline
      values of the Psoriasis Area and Severity Index (PASI). RESULTS: Baseline plasma
      concentrations of both TIMP-1 and MMP-1 (1487 +/- 102 and 21.0 +/- 2.5 ng/mL,
      respectively) were significantly higher (P = 0.02 and 0.03, respectively) than
      normal. Both TIMP-1 and MMP-1 decreased significantly after completion of
      treatment to values similar to normal (1112 +/- 127 and 11.3 +/- 1.3 ng/mL,
      respectively). There was a significant positive correlation (r = 0.522) between
      baseline PASI and TIMP-1 values. Significant differences were observed between
      baseline TIMP-1 concentrations in groups with PASI < 15 and PASI > 20. Baseline
      values (1697 +/- 162 ng/mL) in patients with severe course of the disease (PASI >
      20) were significantly elevated in comparison to normal values. Treatment caused
      a decrease in TIMP-1 plasma concentrations in all groups, but a significant
      difference was noted only in patients with pretreatment PASI > 20. Baseline MMP-1
      concentrations exceeded significantly normal values only in patients with PASI <
      15 (27.2 +/- 6.3 ng/mL) and 15-20 (18.4 +/- 1.4 ng/mL). Treatment caused a
      significant decrease in MMP-1-values in all groups to levels similar to normal.
      CONCLUSIONS: Our results confirm the role of TIMP-1 and MMP-1 in the pathogenesis
      of psoriasis. Pretreatment plasma TIMP-1 increased whereas MMP-1 decreased in
      patients with a more severe course of the disease. However, successful treatment
      causes normalization of these plasma protein concentrations irrespective of
      psoriasis baseline activity.

PMID- 15987286
TI  - Erythema dyschromicum perstans in children: a report of 14 cases.
AB  - BACKGROUND: Erythema dyschromicum perstans (EDP) or ashy dermatosis is a
      peculiar, slowly progressive, macular hyperpigmentation, which leaves a permanent
      discoloration. It is an acquired dermatosis that occurs most frequently in
      Central and South America. EDP usually appears in adults, but some isolated cases
      and small series have been reported in prepubertal children. METHODS: A
      retrospective review of cases of EDP in 10-year-old children or younger, attended
      in a pediatric hospital between 1990 and 2003. RESULTS: We present 14 cases of
      EDC in children 10 years and younger. With an additional 25 cases reported so far
      in the English language literature, a total of 39 children have been described.
      Unlike adult patients, who are most commonly of Hispanic origin, children with
      EDP are usually Caucasian. Other important facts in children with EDP are the
      absence of consistent trigger factors and an eventual improvement or resolution
      of the lesions in 50% of prepubertal patients. CONCLUSION: We suggest that EDP is
      a distinctive clinical entity, different from lichen planus and lichen planus
      pigmentosus, which may be identical to the so-called idiopathic eruptive macular
      pigmentation.

PMID- 15987287
TI  - Screening of Chlamydia trachomatis urogenital infections among the male and
      female population of the Republic of Macedonia.
AB  - BACKGROUND: Noninvasive urine screening for Chlamydia trachomatis infections
      offers a valuable public health tool, that could be of vast importance in
      Chlamydia control programs. OBJECTIVE: The goal was to determine the prevalence
      of C. trachomatis infections among a sexually active population, to define the
      epidemiological factors associated with it, and to develop potential selective
      screening strategies among asymptomatic individuals in the Republic of Macedonia,
      using a highly sensitive and specific DNA amplification method for C.
      trachomatis. STUDY DESIGN: A total of 1435 urine samples, divided into two main
      groups: asymptomatic individuals (n = 1210) and symptomatic patients (n = 225),
      were tested. Samples from the asymptomatic group were collected during routine
      screening programs, while the symptomatic group consisted of patients with
      symptoms of urogenital tract infection, attending sexually transmitted diseases
      (STD) clinics. The presence of C. trachomatis was determined using commercial
      AMPLICOR C. trachomatis Assay (Roche Diagnostic Systems, Inc., Branchburg, NJ,
      USA). RESULTS: The prevalence of C. trachomatis infections among different groups
      was: recruits 0%, soldiers 0.4%, policemen 3.5%, clerks 4.6%, pregnant women 4%,
      and students 4.4%. The average prevalence for both groups (asymptomatic and
      symptomatic) was 2.3%[95% confidence interval (CI): 1.5-3.1%]. The average
      prevalence for the asymptomatic group was 1.6% (95% CI: 0.8-2.4%), while the
      average prevalence for the symptomatic group was 6.2% (95% CI: 3.1-9.3%) which
      were significantly different (P = 0.00003). CONCLUSION: Testing first void urine
      specimens by AMPLICOR C. trachomatis assay is a highly sensitive and specific
      method for diagnosing C. trachomatis infections in men and women. This method
      provides health care workers and public health officials with a new molecular
      amplification assay that uses noninvasive urine specimens for population-based
      screening purposes. The prevalence of C. trachomatis was relatively low among
      asymptomatic individuals. However, selective screening strategies are highly
      recommended for testing the student population in the Republic of Macedonia.

PMID- 15987288
TI  - Clinical and histopathological features of zoonotic cutaneous leishmaniasis in
      Saudi Arabia.
AB  - BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania major is
      a growing public health problem and endemic in many parts of the Kingdom of Saudi
      Arabia. The vector is Phlebotomus papatasi and the animal reservoirs are mainly
      desert rodents. METHODS: In this prospective study, the clinical and
      histopathological features of ZCL in 120 patients are described and classified.
      The majority of these patients (n = 84) were non-Saudi expatriate workers who
      suffered mostly from multiple and severely inflamed nodulo-ulcerative lesions on
      the exposed parts of the body. Saudi patients were mainly children (n = 21) with
      few(1-3) lesions on their limbs or sometimes unique erysipeloid facial lesions.
      RESULTS: Histopathological grouping of ZCL lesions showed four types of
      granulomatous reactions based on the predominant types of inflammatory cells,
      presence or absence of necrosis and ranking of parasitic index. CONCLUSION: A
      possible correlation between histopathologic evolution of ZCL lesions and the
      immune status of the host is discussed.

PMID- 15987289
TI  - A phase I/II randomized, double-blind, placebo-controlled, dose-ranging study
      evaluating the efficacy, safety and pharmacokinetics of ravuconazole in the
      treatment of onychomycosis.
AB  - OBJECTIVE: To determine the effectiveness and safety of ravuconazole in the
      treatment of toenail onychomycosis. DESIGN: A phase I/II randomized, double
      blind, double-dummy, placebo-controlled, dose-ranging study. Four 12-week dosing
      regimens were used: 200 mg/day; 100 mg/week; 400 mg/week and placebo. Subjects
      returned at weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 36 and 48 for assessment.
      Subjects were enrolled at 10 dermatology practices (seven in the United States,
      one in Canada, two in France). SUBJECTS: Adults with distal subungual
      onychomycosis of one great (hallux) toenail (minimum area of 25%), and at least 2
      mm of proximal nail clear of disease were selected. Onychomycosis was confirmed
      by direct microscopy and/or fungal culture. Subjects with conditions known to
      produce abnormal-appearing nails were excluded. One hundred and fifty-one
      subjects were randomized in a 2:2:2:1 ratio to the treatments above. MAIN OUTCOME
      MEASURES: Primary efficacy was the effective cure rate at week 48 (mycological
      cure, and clinical cure or > 30% improvement). RESULTS: Effective cure was found
      in 56% of subjects using 200 mg/day. Effective cure was 10% in subjects receiving
      100 mg/week, 8% of subjects using 400 mg/week, and 15% of subjects using placebo.
      Mycological cure was seen in 59% of subjects in the 200-mg/day group, which was
      significantly higher than the rates found in the other groups. Drug-related
      adverse events were infrequent in all treatment arms. Headache was the most
      frequently reported event. Abnormal laboratory tests were infrequent over the 12
      weeks of dosing. Abnormal laboratory findings with increases beyond normal of
      Grade 2, 3 or 4 were found in 8/148 subjects (5.4%). Only the 200 mg daily
      regimen had a mean plasma steady state concentration of ravuconazole exceeding
      the MIC(90) adjusted for 98% protein binding (3000 ng/mL). CONCLUSIONS: For the
      treatment of onychomycosis, ravuconazole 200 mg/day for 12 weeks is the most
      effective of the regimens investigated. The safety of all regimens was
      acceptable. The concentrations of ravuconazole in the plasma compared to the
      adjusted MIC(90) may be useful in predicting the clinical and mycologic response
      of therapy.

PMID- 15987290
TI  - Poikiloderma of Civatte: a clinical and epidemiological study.
AB  - BACKGROUND: Although a common dermatosis, idiopathic poikiloderma of the face and
      neck has not been studied in depth for decades. OBJECTIVES: To reassess the
      clinical and epidemiological characteristics of poikiloderma of Civatte (PC).
      MATERIAL AND METHODS: Fifty consecutive patients with PC. Evaluation included
      history taking and physical examination. Epidemiological and clinical parameters
      were recorded and analysed. The literature from 1923 until today, was reviewed
      thoroughly. RESULTS: The frequency of PC among dermatologic patients was
      estimated to be 1.4%. There were 34 females (68%) and 16 males in the present
      study. The mean age at diagnosis was 47.8 years for females and 61.7 years for
      males. The majority (88%) had skin phototype II or III. Among females, 26 were at
      their peri-menopausal stage, including three cases of iatrogenic menopause. Four
      patients reported that other blood-related family members also had PC. The v and
      the sides of the neck and the upper chest were most often affected in a symmetric
      distribution. The face (preauricular and parotid region) was involved in 19
      patients (38%). The erythemato-telangiectatic clinical type predominated (58%),
      followed by the mixed (22%) and the pigmented type (20%). Almost half of the
      patients (46%) were symptomatic (itching, burning and 'flushing'). The mean
      duration from onset to diagnosis was 6.2 years according to the patients' report.
      The course was usually slowly progressive (82%) and irreversible. CONCLUSIONS: PC
      shows characteristic features, supporting the theory that it represents a
      distinct entity. It is rather common in Greece. Although menopausal women
      predominated in our cohort, men were not uncommonly affected and were diagnosed
      at an older age. Based on the predominating clinical feature, PC can be
      classified into three clinical forms. Symmetry and sparing of the anatomically
      shaded areas of the neck are highly characteristic for PC. Face involvement was
      not as common and as severe as it had been considered in the past. Recognition of
      clinical type is important for the selection of the most appropriate treatment,
      which, despite the advent of novel modalities, remains problematic.

PMID- 15987291
TI  - Reactivity to euro coins and sensitization thresholds in nickel-sensitive
      subjects.
AB  - BACKGROUND: The 1- and the 2-euro coins consist of nickel alloys, which release
      nickel. The nickel released by far exceeds the amount allowed by the European
      Union Nickel Directive referring to products intended to come into direct and
      prolonged contact with the skin. As there is only temporary contact with the
      skin, the clinical relevance of nickel-containing coins with regard to nickel
      dermatitis is a matter of debate, although there is evidence that the nickel
      released from the coins affects some nickel-sensitive subjects through
      occupational exposure. OBJECTIVES: Our aim was to study skin reactivity to euro
      coins, and to correlate the frequency and intensity of coin patch test responses
      to sensitization thresholds to nickel. PATIENTS AND METHODS: Sixty-four nickel
      sensitized and 30 non-nickel-sensitized subjects were patch tested with serial
      dilutions of nickel sulfate (5, 1, 0.5, 0.1, 0.05, 0.01 and 0.005% in distilled
      water) and with coins. Italian coins (500, 200, 100 and 50 lira) and euro coins
      (2 and 1 euros, 20 and 5 euro cents) were used for patch testing and compared.
      RESULTS: The application of 1- and 2-euro coins to the skin induced eczematous
      reactions, being more frequent and intense in comparison with those provoked by
      other coins. A correlation between intensity of responses to coin patch tests and
      sensitization threshold to nickel was observed. Patients with the strongest
      reactions to 1- and 2-euro coins showed positive responses to the lowest nickel
      concentrations. CONCLUSIONS: The nickel content in euro coins represents a
      possible health hazard, especially for highly nickel-sensitive subjects. We
      recommend that nickel sulfate patch tests should be performed at different
      concentrations to determine sensitization thresholds at least in individuals with
      occupational exposure to coins.

PMID- 15987292
TI  - A7445G mtDNA mutation present in a Portuguese family exhibiting hereditary
      deafness and palmoplantar keratoderma.
AB  - Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible
      for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with
      deafness without any additional features. To date, only a few cases have been
      described. We report a Portuguese pedigree presenting an inherited combination of
      NEPPK and sensorineural deafness compatible with maternal transmission. Clinical
      expression and age of onset of NEPPK and deafness were variable. Normal
      expression patterns of epidermal keratins and filaggrin, intercellular junction
      proteins including connexin 26, loricrin and cornified envelope proteins, were
      observed. Molecular analysis revealed that all the affected members, previously
      screened for Cx26 mutations with negative results, presented the mtDNA A7445G
      point mutation in the homoplasmic form. To our knowledge, this is the fifth
      family in whom inherited NEPPK and hearing loss are related to this mitochondrial
      mutation.

PMID- 15987293
TI  - A new case of semicircular lipoatrophy associated with repeated external
      microtraumas and review of the literature.
AB  - We present a new case of semicircular lipoatrophy whose lesions disappeared after
      2 months of avoiding a repeated trauma in that area. It seems that this is the
      only associated aetiological factor, and this entity is perhaps a consequence of
      certain postural habits. The repeated microtraumas would damage the fatty tissue
      giving rise to the histopathological findings described, which are compatible
      with traumatic panniculitis. In conclusion, repeated microtraumas may be the
      aetiological factor in these cutaneous lesions. Other data in favour of this
      hypothesis are the disappearance of the lesions after avoiding the mechanical
      trauma, the fact that there were other affected people at work, and that this
      factor has also been identified in the majority of cases reported previously.

PMID- 15987294
TI  - Tumorous variant of scleromyxedema. Successful therapy with intravenous
      immunoglobulins.
AB  - We present an unusual tumorous variety of scleromyxedema mimicking facies leonina
      in lymphoma. In spite of pronounced and widespread cutaneous changes,
      hypergammaglobulinaemia and paraproteinaemia, the general condition of the
      patient was satisfactory, there was no internal involvement and no symptoms of
      any malignancy. Initially, melphalan and corticosteroids were applied but were
      not effective. High-dose intravenous immunoglobulin (IVIG) therapy had dramatic
      effect, and after five 5-day monthly courses the tumours almost regressed and the
      skin became less hard. After a further five courses in the following year there
      was complete clearance, which was sustained without any therapy for 1 year (until
      now). IVIG appears to be the therapy of choice for scleromyxedema. We stress,
      however, that at the start of therapy, IVIG applications should be supplemented
      with small doses of melphalan and/or corticosteroids.

PMID- 15987295
TI  - Impetigo herpetiformis: menstrual exacerbations for 7 years postpartum.
AB  - Impetigo herpetiformis (IH) is a rare pustular dermatosis that shares striking
      clinical and histological similarities to generalized pustular psoriasis. The
      case of a 26-year-old primigravida with IH progressing in the 30th week of her
      pregnancy is presented. The peculiarity of our presentation relies on the
      reappearance of the disease postpartum. Monthly exacerbations during menstruation
      lasted for 7 years. Some probable clues regarding the pathogenesis of IH are
      suggested.

PMID- 15987296
TI  - Childhood granulomatous periorificial dermatitis: lupus miliaris disseminatus
      faciei in children?
AB  - BACKGROUND: Childhood granulomatous periorificial dermatitis (CGPD) is a
      granulomatous disease characterized by monomorphous, small papular eruptions
      around the mouse, nose and eyes, and is thought to be closely related to perioral
      dermatitis. This condition has always been believed to occur more commonly in
      dark-skinned patients; however, recent observations have revealed CGPD to occur
      also in white patients. OBSERVATION: We report an 11-year-old Japanese boy with
      the characteristic features of CGPD. Although sarcoidosis and acne/granulomatous
      rosacea could be differentiated from CGPD, we could find no essential differences
      between CGPD and lupus miliaris disseminatus faciei (LMDF). The cases of LMDF in
      children, which were recorded in the Japanese literature, had highly similar
      clinicopathological features to those of CGPD. This case responded dramatically
      to topical tacrolimus in combination with the oral administration of minocycline.
      CONCLUSIONS: The entity 'facial idiopathic granulomas with regressive evolution'
      is considered to include LMDF (a common adult form), CGPD (a rare childhood form)
      and perioral dermatitis (a peculiar form exacerbated by topical corticosteroids).
      Topical tacrolimus may be recommended as one of the therapies for LMDF as well as
      CGPD.

PMID- 15987297
TI  - Vesiculous prurigo pigmentosa in a 13-year-old girl: good response to
      isotretinoin.
AB  - Prurigo pigmentosa is a rare inflammatory disease of unknown origin, first
      reported from Japan, with only 33 cases described in non-Japanese patients. We
      describe a 13-year-old girl with a pruriginous symmetrical eruption of papules
      and vesicles affecting her back, neck and chest of 1 month duration. She
      remembered a similar, but lighter eruption, 2 months before. As the initial
      diagnosis was of a vesiculobullous form of Darier disease, treatment with
      isotretinoin 40 mg/day was started with good response. Histological study showed
      a superficial perivascular and interstitial dermatitis composed predominantly of
      lymphocytes. The epidermis was spongiotic, with exocytosis of lymphocytes and
      some neutrophils and necrotic keratinocytes. All these findings were consistent
      with prurigo pigmentosa. The lesions resolved leaving a light brown reticulate
      hyperpigmentation. Prurigo pigmentosa has never been reported in prepubescent
      patients, the vesiculobullous forms are unusual, and the only treatments used
      previously are sulphonamides, tetracyclines and macrolides. We report a 13-year
      old Caucasian girl with vesiculobullous prurigo pigmentosa successfully treated
      with isotretinoin.

PMID- 15987298
TI  - Degos disease with an inconspicuous clinical course.
AB  - BACKGROUND: Degos disease is a rare systemic disorder with involvement of the
      skin and visceral organs, leading to death in about 50% of cases within 1 or 2
      years. In recent years, several cases with cutaneous lesions only have been
      recognized. METHODS: We report on a young male patient presenting with single
      inconspicuous papules with bluish/black centres on the trunk and the upper limbs
      that, upon healing turn white. These lesions recurred on different locations over
      the past 6 years, and were never more than two to three at one time. RESULTS:
      Histopathological examinations revealed archetypal features for Degos disease.
      The patient had no other complaints, neither visceral organs nor the central
      nerve system were involved. Laboratory examinations were within normal range.
      CONCLUSIONS: This case increases the number of reports on a benign course of
      Degos disease. It raises the question if the 'malignant' and the 'benign' course
      of the disease represent two distinct diseases or variants of a systemic
      vasculitis with unknown cause.

PMID- 15987299
TI  - Extensive nodular cutaneous amyloidosis: an unusual presentation.
AB  - Amyloidosis is characterized by the deposition of a group of unrelated proteins
      leading to changes in tissue architecture and function. The nodular variant is
      the rarest form of the cutaneous amyloidoses. We report a patient with localized
      nodular amyloidosis without systemic amyloid involvement or paraproteinaemia
      after 6 years of follow-up. The unusual aspects of our case were a plaque
      presentation rather than nodular, and the disseminated pattern observed.

PMID- 15987300
TI  - Adamantiades-Behcet's disease, deep venous thrombosis and anticardiolipin
      antibodies: report of two cases.
AB  - Vascular thrombosis was found in different proportions of patients with
      Adamantiades-Behcet's disease (ABD), depending on the ethnicity of the population
      under study. Various thrombophilic factors, including the levels of
      anticardiolipin antibodies (ACA), were investigated for their role in the
      thrombotic process with conflicting results. The prevalence of ACA varies
      considerably in different studies, but their presence has not been associated
      with increased risk for vascular thrombosis. We present two cases with ABD, deep
      venous thrombosis (DVT) and elevated levels of ACA that fulfil the criteria for
      both ABD and antiphospholipid syndrome (APS).

PMID- 15987301
TI  - Alpha1-antitrypsin deficiency-associated panniculitis: case report and review of
      treatment options.
AB  - Alpha(1)-antitrypsin deficiency, a relatively frequent mutation in the
      population, is associated with the development of panlobular emphysema and liver
      cirrhosis. The deficiency is in rare cases associated with the development of
      panniculitis, and very differentiated clinical courses have been reported in the
      literature. We report a case of panniculitis in a patient with alpha(1)
      antitrypsin deficiency and describe briefly the pathophysiology of the disease
      and current treatment possibilities.

PMID- 15987302
TI  - Circumscribed palmar hypokeratosis: clinical evolution and ultrastructural study
      after prolonged treatment with topical calcipotriol.
AB  - Circumscribed palmar hypokeratosis is a recently described condition that
      consists of a solitary area of depressed skin affecting the palm (or sole). Its
      histopathological features include a thinned horny layer, a slightly diminished
      granular cell layer, and intraepidermal vacuolated cells. Prolonged treatment
      with topical calcipotriol resulted in complete recovery of the affected zone in
      the case reported here. A second biopsy of the lesion taken at around the fourth
      year of therapy showed a normalization of the granular layer, a reduction in the
      intraepidermal vacuolated cells, and a somewhat thicker horny layer. An
      ultrastructural study carried out at the same time showed a reduction in keratin
      bundles and keratohyalin granules, and an increase in lipid droplets up to the
      horny layer. These findings and the therapeutic response to topical calcipotriol
      support the concept that circumscribed palmar hypokeratosis is a focalized
      abnormal keratinization defect morphologically expressed at the granular and
      horny layers.

PMID- 15987303
TI  - Recommendations for the topical treatment of psoriasis.
AB  - Several topical treatments are available for patients with psoriasis. Although
      individualization of the treatment remains important, there is a need for
      treatment recommendations to identify the best treatment out of the available
      treatments and to help with improvement in treatment compliance. In this
      communication we give our views on the assessment of severity of psoriasis. We
      provide recommendations for selection of treatments, reconciling the clearance
      phase and the long-term management. Finally, we provide recommendations for the
      treatment of particular localizations: the scalp and psoriasis at sensitive
      sites.

PMID- 15987305
TI  - The birhombic transposition flap to repair cutaneous lesions.

PMID- 15987304
TI  - Multiple myeloma with scleroderma-like changes.
AB  - We present a case of a patient who presented concomitantly with generalized
      pruritus, brownish sclerodermatous plaques, sclerodactyly and a monoclonal band
      for IgG-kappa. The patient was diagnosed as having multiple myeloma by bone
      marrow examination. The rapidly progressive evolution with acute anuric renal
      failure, malignant hypertension and the skin sclerosis seem to be related to the
      neoplastic disorder. The scleroderma-like changes have to be differentiated from
      systemic scleroderma.

PMID- 15987306
TI  - Cutaneous Mycobacterium chelonae I infection extending in the lower extremities
      in a renal transplanted patient.

PMID- 15987307
TI  - Congenital naevus with 'Spitzoid starting' in an 8-year-old child: dermoscopic
      and histological features.

PMID- 15987308
TI  - Erythema multiforme associated with sporotrichosis.

PMID- 15987309
TI  - Keloid secondary to therapeutic cupping: an unusual complication.

PMID- 15987310
TI  - Amalgam fillings associated with increased matrix metalloproteinase 9 levels in
      human saliva.

PMID- 15987312
TI  - Squamous cell carcinoma arising from lupus vulgaris.

PMID- 15987311
TI  - Nevoid basal cell carcinoma syndrome associated with unilateral renal agenesis:
      acceleration of basal cell carcinomas following radiotherapy.

PMID- 15987313
TI  - Angina bullosa haemorrhagica--a localized amyloidosis?

PMID- 15987314
TI  - Redness, a possible signpost for malignant melanoma.

PMID- 15987315
TI  - Intralesional tuberculin for treatment of refractory warts.

PMID- 15987316
TI  - Skin lesions of lymphomatoid papulosis with a white halo.

PMID- 15987317
TI  - Erythema nodosum migrans.

PMID- 15987318
TI  - Hepatitis C virus RNA in the cutaneous eruption but not in the symptom-free skin
      from patient with prurigo simplex and chronic C hepatitis.

PMID- 15987319
TI  - Generalized pustular psoriasis following withdrawal of short-term cyclosporin
      therapy for psoriatic arthritis.

PMID- 15987322
TI  - Toward optimal screening strategies for older women. Costs, benefits, and harms
      of breast cancer screening by age, biology, and health status.
AB  - CONTEXT: Optimal ages of breast cancer screening cessation remain uncertain.
      OBJECTIVE: To evaluate screening policies based on age and quartiles of life
      expectancy (LE). DESIGN AND POPULATION: We used a stochastic model with proxies
      of age-dependent biology to evaluate the incremental U.S. societal costs and
      benefits of biennial screening from age 50 until age 70, 79, or lifetime. MAIN
      OUTCOME MEASURES: Discounted incremental costs per life years saved (LYS).
      RESULTS: Lifetime screening is expensive (151,434 dollars per LYS) if women have
      treatment and survival comparable to clinical trials (idealized); stopping at age
      79 costs 82,063 dollars per LYS. This latter result corresponds to costs
      associated with an LE of 9.5 years at age 79, a value expected for 75% of 79-year
      olds, about 50% of 80-year-olds, and 25% of 85-year-olds. Using actual treatment
      and survival patterns, screening benefits are greater, and lifetime screening of
      all women might be considered (114,905 dollars per LYS), especially for women in
      the top 25% of LE for their age (50,643 dollars per LYS, life expectancy of
      approximately 7 years at age 90). CONCLUSIONS: If all women receive idealized
      treatment, the benefits of mammography beyond age 79 are too low relative to
      their costs to justify continued screening. However, if treatment is not ideal,
      extending screening beyond age 79 could be considered, especially for women in
      the top 25% of life expectancy for their age.

PMID- 15987323
TI  - Does experience matter? A comparison of the practice of attendings and residents.
AB  - OBJECTIVE: To compare the utilization of health care resources and patterns of
      chronic disease care by patients of medical residents and patients of their
      attending physicians. MATERIALS AND METHODS: This study involved a longitudinal
      cohort of 14,554 patients seen over a 1-year period by 149 residents and 36
      attendings located in an urban academic medical center. Data were acquired
      prospectively through a practice management system used to order tests, write
      prescriptions, and code ambulatory visits. We assessed resource utilization by
      measuring the total direct costs of care over a 1-year period, including
      ambulatory and inpatient costs, and the numbers and types of resources used.
      RESULTS: Residents' patients were similar to attendings' patients in age and
      gender, but residents' patients were more likely to have Medicaid or Medicare and
      to have a higher burden of comorbidity. Total annual ambulatory care costs were
      almost 60% higher for residents' patients than for attendings' patients in
      unadjusted analyses, and 30% higher in analyses adjusted for differences in case
      mix (adjusted mean 888 dollars vs 750 dollars; P=.0001). The primary cost drivers
      on the outpatient side were consultations and radiological procedures. Total
      inpatient costs were almost twice as high for residents' patients compared to
      attendings' patients in unadjusted analyses, but virtually identical in analyses
      adjusted for case mix differences (adjusted mean of 849 dollars vs 860 dollars).
      Admission rates were almost double for residents' patients. Total adjusted costs
      for residents' patients were slightly, but not significantly, higher than for
      attendings' patients (adjusted mean 1,651 dollars vs 1,540 dollars; P>.05).
      Residents' and attendings' patients generally did not differ in the patterns of
      care for diabetes, asthma/chronic obstructive pulmonary disease (COPD),
      congestive heart failure, ischemic heart disease, and depression, except that
      residents' patients with asthma/COPD, ischemic heart disease, and diabetes were
      admitted more frequently than attendings' patients. CONCLUSIONS: Our results
      indicate that residents' patients had higher costs than attendings' patients, but
      the differences would have been seriously overestimated without adjustment. We
      conclude that it costs about 7% more for residents to manage patients than for
      attendings. On the ambulatory side, the larger number of procedures and consults
      ordered for residents' patients appears to drive the higher costs.

PMID- 15987324
TI  - Who can't pay for health care?
AB  - BACKGROUND: In an era of rising health care costs, many Americans experience
      difficulty paying for needed health care services. With costs expected to
      continue rising, changes to private insurance plans and public programs aimed at
      containing costs may have a negative impact on Americans' ability to afford care.
      OBJECTIVES: To provide estimates of the number of adults who avoid health care
      due to cost, and to assess the association of income, functional status, and type
      of insurance with the extent to which people with health insurance report
      financial barriers. RESEARCH DESIGN: Cross-sectional observational study using
      data from the Commonwealth Fund 2001 Health Care Quality Survey, a nationally
      representative telephone survey. PARTICIPANTS: U.S. adults age 18 and older
      (N=6,722). MEASURES: Six measures of avoiding health care due to cost, including
      delaying or not seeking care; not filling prescription medicines; and not
      following recommended treatment plan. RESULTS: The proportion of Americans with
      difficulty affording health care varies by income and health insurance coverage.
      Overall, 16.9% of Americans report at least 1 financial barrier. Among those with
      private insurance, the poor (28.4%), near poor (24.3%), and those with functional
      impairments (22.9%) were more likely to report avoiding care due to cost. In
      multivariate models, the uninsured are more likely (OR, 2.3; 95% CI, 1.7 to 3.0)
      to have trouble paying for care. Independent of insurance coverage and other
      demographic characteristics, the poor (OR, 3.6; 95% CI, 2.1 to 4.6), near poor
      (OR, 2.1; 95% CI, 1.9 to 3.7), and middle-income (OR, 1.8; 95% CI, 1.3 to 2.5)
      respondents as well as those with functional impairments (OR, 1.6; 95% CI, 1.3 to
      2.0) are significantly more likely to avoid care due to cost. CONCLUSIONS:
      Privately and publicly insured individuals who have low incomes or functional
      impairments encounter significant financial barriers to care despite having
      health insurance. Proposals to expand health insurance will need to address these
      barriers in order to be effective.

PMID- 15987325
TI  - Caregiver burden and depression among informal caregivers of HIV-infected
      individuals.
AB  - BACKGROUND: Few studies have examined the factors associated with depression in
      informal caregivers of HIV-infected persons. OBJECTIVE: To investigate the
      relationship between depression and caregiver burden among informal caregivers of
      HIV-infected individuals. DESIGN: Cross-sectional study using baseline data from
      an ongoing randomized trial of a supportive telephone intervention. PARTICIPANTS:
      One hundred seventy-six dyads of HIV patients and their informal caregiver.
      MEASUREMENTS: Depression was defined as a Beck Depression Inventory >10. A
      Caregiver Strain Index >6 identified informal caregivers with a high caregiver
      burden. We used logistic regression to identify characteristics that were
      associated with depression in the informal caregiver. RESULTS: Informal
      caregivers were 42 years old (SD, 13), 53% female, 59% nonwhite, and 30% had
      education beyond high school. Forty-seven percent of informal caregivers were the
      patient's partner, 18% a friend, and 35% a family member. Twenty-seven percent of
      informal caregivers had a high caregiver burden, and 50% were depressed. We found
      significantly greater odds of informal caregiver depression with high caregiver
      burden (OR, 6.08; 95% CI, 2.40 to 15.4), informal caregiver medical comorbidity
      besides HIV (OR, 2.32; 95% CI, 1.09 to 4.92), spending all day together (OR,
      3.92; 95% CI, 1.59 to 9.69), having to help others besides the HIV patient (OR,
      2.55; 95% CI, 1.14 to 5.74), and duration of the HIV patient's diagnosis (OR,
      1.01 per month; 95% CI, 1.00 to 1.01). CONCLUSIONS: High caregiver burden was
      strongly associated with depression among HIV-infected individuals' informal
      caregivers, who themselves had difficult life circumstances. Informal caregivers
      of HIV patients may be in need of both mental health services and assistance in
      caregiving.

PMID- 15987326
TI  - The validity of a single-question self-report of erectile dysfunction. Results
      from the Massachusetts Male Aging Study.
AB  - OBJECTIVE: To determine how well a single question of self-reported erectile
      dysfunction compares to a gold standard clinical urologic examination. DESIGN AND
      SETTING: Clinical validation study nested within the Massachusetts Male Aging
      Study (MMAS), which is an observational cohort study of aging and health in a
      population-based random sample of men. MEASUREMENT: During an in-person
      interview, men were asked to respond to a single-question self-report of erectile
      dysfunction. A subsample of MMAS participants was then subjected to a clinical
      urologic examination to obtain a clinical diagnosis of erectile dysfunction.
      PARTICIPANTS: One hundred thirty-nine men 55 to 85 years of age from the MMAS.
      RESULTS: Complete data were available from 137 men. Erectile dysfunction (ED)
      measured by self-report and independent urologic examination were strongly
      correlated (Spearman r=.80). Receiver operating curve analysis showed that the
      self-reported ED item accurately predicts the clinician-diagnosed ED (area under
      the curve [AUC]=0.888). Stratum-specific likelihood ratios (95% confidence
      intervals) for self-reports predicting the gold standard were: no ED=0.11 (0.06
      to 0.22), minimal ED=1.48 (0.67 to 3.26), moderate ED=8.57 (1.21 to 60.65), and
      complete ED=12.69 (1.81 to 88.79). These data indicate that men diagnosed with ED
      by urologic examination can be distinguished from men not diagnosed with ED by
      urologic examination if the respondent self-reported no, moderate, or complete
      ED. CONCLUSION: Our single-question self-report accurately identifies men with
      clinically diagnosed ED, and may be useful as a referral screening tool in both
      research studies and general practice settings.

PMID- 15987327
TI  - Do blood tests cause anemia in hospitalized patients? The effect of diagnostic
      phlebotomy on hemoglobin and hematocrit levels.
AB  - OBJECTIVE: To determine whether phlebotomy contributes to changes in hemoglobin
      and hematocrit levels in hospitalized general internal medicine patients. DESIGN:
      Retrospective cohort study. SETTING: General internal medicine inpatient service
      at a tertiary care hospital. PARTICIPANTS: All adult patients discharged from the
      Toronto General Hospital's internal medicine service between January 1 and June
      30, 2001. A total of 989 hospitalizations were reviewed and 404 hospitalizations
      were included in our analysis. MEASUREMENTS AND MAIN RESULTS: Mean (SD)
      hemoglobin and hematocrit changes during hospitalization were 7.9 (12.6) g/L
      (P<.0001) and 2.1% (3.8%) (P<.0001), respectively. The mean (SD) volume of
      phlebotomy during hospital stay was 74.6 (52.1) mL. On univariate analysis,
      changes in hemoglobin and hematocrit were predicted by the volume of phlebotomy,
      length of hospital stay, admission hemoglobin/hematocrit value, age, Charlson
      comorbidity index, and admission intravascular volume status. The volume of
      phlebotomy remained a strong predictor of drop in hemoglobin and hematocrit after
      adjusting for other predictors using multivariate analysis (P<.0001). On average,
      every 100 mL of phlebotomy was associated with a decrease in hemoglobin and
      hematocrit of 7.0 g/L and 1.9%, respectively. CONCLUSIONS: Phlebotomy is highly
      associated with changes in hemoglobin and hematocrit levels for patients admitted
      to an internal medicine service and can contribute to anemia. This anemia, in
      turn, may have significant consequences, especially for patients with
      cardiorespiratory diseases. Knowing the expected changes in hemoglobin and
      hematocrit due to diagnostic phlebotomy will help guide when to investigate
      anemia in hospitalized patients.

PMID- 15987328
TI  - Physician responses to ambiguous patient symptoms.
AB  - OBJECTIVE: To examine how primary care physicians respond to ambiguous patient
      symptom presentations. DESIGN: Observational study, using thematic analysis
      within a larger cross-sectional study employing standardized patients (SPs), to
      describe physician responses to ambiguous patient symptoms and patterns of
      physician-patient interaction. SETTING: Community-based primary care offices
      within a metropolitan area. PARTICIPANTS: Twenty-three primary care physicians
      (internists and family physicians). METHOD: Participating physicians had 2
      unannounced SP visits randomly inserted into their daily practice schedules and
      the visits were audiotaped and transcribed. A coding system focusing on physician
      responses to concerned patients presenting with ambiguous symptoms was developed
      through an inductive process. Thematic analyses were then applied to coded data.
      RESULTS: Physicians' responses to ambiguous symptoms were categorized into 2
      primary patterns: high partnering (HP) and usual care (UC). HP was characterized
      by greater responsiveness to patients' expression of concern, positivity,
      sensitivity to patients' clues about life circumstances, greater acknowledgment
      of symptom ambiguity, and solicitation of patients' perspectives on their
      problems. UC was characterized by denial of ambiguity and less inclusion of
      patients' perspectives on their symptoms. Neither HP physicians nor UC physicians
      actively included patients in treatment planning. CONCLUSIONS: Primary care
      physicians respond to ambiguity by either ignoring the ambiguity and becoming
      more directive (UC) or, less often, by acknowledging the ambiguity and attempting
      to explore symptoms and patient concerns in more detail (HP). Future areas of
      study could address whether physicians can learn HP behaviors and whether HP
      behaviors positively affect health outcomes.

PMID- 15987330
TI  - Evaluation of a women's safe shelter experience to teach internal medicine
      residents about intimate partner violence. A randomized controlled trial.
AB  - Although intimate partner violence (IPV) remains a major public health problem,
      physicians often fail to screen female patients. Reported IPV training approaches
      suffer from weak study designs and limited outcome assessments. We hypothesized
      that an educational experience for residents at a women's safe shelter would have
      significantly greater impact on IPV competencies, screening, and care for victims
      than a workshop seminar alone. In a pre-post randomized controlled trial, we
      compared residents exposed to the workshop seminar alone (controls) to residents
      exposed to these methods plus an experience at a women's safe shelter (cases).
      Competencies were assessed by written questionnaire and included knowledge,
      skills, attitudes, resource awareness, and screening behaviors. Of the 36
      residents in the trial, 22 (61%) completed both pre- and postquestionnaires.
      Compared to controls, cases showed significantly greater pre-post improvement in
      the knowledge composite subscale. There were no significant differences between
      cases and controls in the subscales of skills, attitudes, or resource awareness.
      Cases increased their self-reported screening frequency but this did not differ
      significantly from the controls. Enhancing traditional IPV curriculum with a
      women's safe shelter educational experience may result in small improvements in
      residents' knowledge about IPV.

PMID- 15987329
TI  - Not all patients want to participate in decision making. A national study of
      public preferences.
AB  - BACKGROUND: The Institute of Medicine calls for physicians to engage patients in
      making clinical decisions, but not every patient may want the same level of
      participation. OBJECTIVES: 1) To assess public preferences for participation in
      decision making in a representative sample of the U.S. population. 2) To
      understand how demographic variables and health status influence people's
      preferences for participation in decision making. DESIGN AND PARTICIPANTS: A
      population-based survey of a fully representative sample of English-speaking
      adults was conducted in concert with the 2002 General Social Survey (N= 2,765).
      Respondents expressed preferences ranging from patient-directed to physician
      directed styles on each of 3 aspects of decision making (seeking information,
      discussing options, making the final decision). Logistic regression was used to
      assess the relationships of demographic variables and health status to
      preferences. MAIN RESULTS: Nearly all respondents (96%) preferred to be offered
      choices and to be asked their opinions. In contrast, half of the respondents
      (52%) preferred to leave final decisions to their physicians and 44% preferred to
      rely on physicians for medical knowledge rather than seeking out information
      themselves. Women, more educated, and healthier people were more likely to prefer
      an active role in decision making. African-American and Hispanic respondents were
      more likely to prefer that physicians make the decisions. Preferences for an
      active role increased with age up to 45 years, but then declined. CONCLUSION:
      This population-based study demonstrates that people vary substantially in their
      preferences for participation in decision making. Physicians and health care
      organizations should not assume that patients wish to participate in clinical
      decision making, but must assess individual patient preferences and tailor care
      accordingly.

PMID- 15987331
TI  - Placebo HAART regimen as a method for teaching medication adherence issues to
      students.
AB  - Placebo medication regimens may help educate students about adherence issues. In
      this randomized trial, 23 third-year medical students took a 2-week placebo
      regimen mimicking highly active antiretroviral therapy (HAART) during their
      medicine clerkship; 15 students served as controls. Although no effect was
      demonstrated from this intervention on an evaluation instrument examining
      attitudes and beliefs about medication nonadherence, all 23 student-subjects
      agreed in postintervention interviews that the experience was useful and had
      learning value. Representative comments from the 19 subjects who expanded their
      interview responses portray this intervention as an eye-opening and unique method
      for teaching students about medication adherence issues.

PMID- 15987332
TI  - The corporate coauthor.
AB  - Drug marketing techniques include the sponsorship of articles signed by academic
      physicians or researchers and submitted to peer-reviewed medical journals. Some
      of these articles are authored or coauthored by ghostwriters who work for
      pharmaceutical companies or medical education companies hired by pharmaceutical
      companies. Conflicts of interest may be difficult to detect in the subset of
      articles and presentations sponsored by pharmaceutical companies that never
      mention the targeted drug, but focus on stimulating the perceived need for the
      targeted drug or highlighting problems with competing drugs. The current
      voluntary standards for declaring conflicts of interest to readers of medical
      journals and audiences at medical conferences are inadequate. A public database
      that contains conflicts of interest of physicians and researchers would be
      useful.

PMID- 15987333
TI  - Ghost writing initiated by commercial companies.

PMID- 15987334
TI  - Scientific discourse, corporate ghostwriting, journal policy, and public trust.

PMID- 15987335
TI  - The use of life expectancy in cancer screening guidelines. Moving with caution
      from model-based evidence to evidence-based guidelines.

PMID- 15987336
TI  - Uncertainty, competence, and opioids.

PMID- 15987337
TI  - Laceration repair.

PMID- 15987338
TI  - Mononuclear cell subsets in bronchoalveolar lavage fluid during Dictyocaulus
      viviparus infection of calves: a potential role for gamma/delta TCR-expressing
      cells in airway immune responses?
AB  - Mononuclear cell populations in the lungs of calves infected with Dictyocaulus
      viviparus were studied during primary infection and reinfection in order to
      identify cells involved in development of protective immunity to parasitic
      bronchitis. Three groups of calves were either inoculated with 500 third-stage
      larvae at both weeks 0 and 10 (n = 6), inoculated only at week 10 (n = 6), or
      remained uninfected (n = 3). The animals were monitored weekly by collection of
      bronchoalveolar lavage fluid (BALF), blood and faeces. Among mononuclear BALF
      cell populations, the gamma/delta TCR-expressing cells showed a pronounced
      transient increase in proportion as well as in relative cell size 2 weeks post
      primary infection, whereas CD4-, CD8-, Ig- and CD14-expressing cells showed no
      significant differences related to the infection. The increase in gamma/delta TCR
      expressing cells coincided with significantly increased proportions of
      eosinophils and recovery of adult worms in BALF. After reinfection, gamma/delta
      TCR-expressing cells increased again, but not until week 3 post inoculation,
      whereas eosinophils were increased by week 2 and reached higher levels than after
      primary infection. After reinfection, establishment of D. viviparus was less
      successful than after primary infection. In conclusion, these results indicate a
      role for gamma/delta TCR-expressing lymphocytes in the pathogenesis of D.
      viviparus infection.

PMID- 15987339
TI  - Secretory antibodies against Giardia intestinalis in lactating Nicaraguan women.
AB  - Secretory IgA (sIgA) antibodies are important in the host defence against the
      intestinal protozoan parasite Giardia intestinalis. However, few antigens have
      been identified. In this study 100 milk and saliva samples from lactating women,
      living in an endemic region (Leon, Nicaragua), were screened for the presence of
      antibodies against G. intestinalis. Most milk and saliva samples contained anti
      Giardia antibodies (59% and 52%, respectively), with a mean sIgA content 50 times
      higher in milk than in saliva. The positive samples reacted with trophozoite
      membrane, flagella and cytoplasmic antigens. Western blot analysis showed that
      milk and saliva anti-Giardia sIgA recognized up to 16 different Giardia proteins
      in the molecular weight region 20-165 kDa. Two-dimensional Western blotting
      showed that the major immunoreactive proteins were the same as the immunoreactive
      proteins identified by serum from acute giardiasis patients in a non-endemic
      country. The major difference was a stronger reactivity against the variant
      surface proteins (VSPs) in the milk samples. Milk sIgAs also recognized
      recombinant Giardia proteins such as alpha-1 giardin, ornithine carbamoyl
      transferase, VSP-4EX, arginine deaminase and alpha-enolase. These antigens will
      be important targets in the development of new immunodiagnostic tools and
      vaccines.

PMID- 15987340
TI  - Parasite-specific IgM plays a significant role in the protective immune response
      to asexual erythrocytic stage Plasmodium chabaudi AS infection.
AB  - A comparison of Plasmodium chabaudi AS infection in BALB/c and BALB/c IgM
      deficient mice demonstrated a protective role for IgM during infection. IgM-/-
      mice, unlike microMT mice, display competent B cell humoral immune responses.
      Increased susceptibility of IgM-/- mice was demonstrated by increased mortality,
      an advanced ascending infection and higher peak parasitaemia, as well as enhanced
      anaemia and weight loss compared with wild-type mice. The recrudescent
      parasitaemias were also higher in the IgM-/- mice. Early specific IgM production
      in P. chabaudi-infected wild-type mice was followed by IgG1 and IgG2a production,
      while IgG1 and IgG2a production in IgM-/- mice was preceded by specific IgD
      production. No protective role for natural IgM against P. chabaudi AS infection
      was detected as passive transfer of naive WT serum into IgM-/- mice did not alter
      the disease outcome or reduce parasite numbers. Passive transfer of WT antiserum,
      containing predominantly specific IgM, into IgM-/- mice delayed the ascending
      parasitaemia and reduced mortality. Similarly, coating parasitized red blood
      cells with WT antiserum, but not IgM-/- antisera, prior to infection also
      slightly delayed the ascending acute parasitaemia. Specific IgM therefore plays
      an important role in the limitation of parasite replication during asexual
      erythrocytic P. chabaudi AS infection.

PMID- 15987341
TI  - Comparative dynamics and phenotype of the murine immune response to Trichinella
      spiralis and Trichinella pseudospiralis.
AB  - Infection of NIH mice with Trichinella spiralis and Trichinella pseudospiralis
      results in qualitatively comparable immune responses. Antigen-specific
      proliferation by mesenteric lymph node cells was transient and temporally
      associated with intestinal infection, but in contrast was sustained throughout
      infection by splenocytes. Early cytokine production by mesenteric lymph node
      cells was dominated by interleukin 10, but also IL-5 and IL-4, with rapid
      resolution following parasite expulsion from the gut. Splenocytes showed a mixed
      profile of cytokine production, although again dominated by IL-10 and sustained
      over 60 days of infection. All antibody classes were evident, with early
      production of IgA and IgG1, and subsequent secretion of other subclasses
      including IgG2a. Granulocytic infiltration of the spleen was significantly
      greater in T. spiralis infection. The concentration of serum corticosterone
      generally remained within normal boundaries, although was raised by day 60 in T.
      spiralis-infected mice. We conclude that the systemic suppression of inflammation
      reported for T. pseudospiralis does not result from selective induction of
      regulatory cytokines, or a major difference in the immune response to infection
      with T. spiralis.

PMID- 15987342
TI  - Schistosoma infection inhibits cellular immune responses to core HCV peptides.
AB  - Patients coinfected with hepatitis C virus (HCV) and the trematode, Schistosoma
      mansoni, have an increased incidence of viral persistence and accelerated
      fibrosis. To investigate immunological mechanisms responsible for this more
      aggressive natural history of HCV, the core HCV-specific T-cell responses were
      analysed in 44 donated blood units rejected because they had antibodies to HCV
      (anti-HCV). Half also had anti-S. mansoni antibodies, evidence of past or active
      infection. HCV-specific ELISPOT responses were examined using pools of 180
      overlapping 9-mer peptides with offsets of one covering the core of HCV genotype
      4a. Comparison of T-cell responses in blood units positive for both anti-HCV and
      anti-Schistosoma antibodies with blood units positive only for anti-HCV
      antibodies showed a significant decrease in core-specific T-cell IFN-gamma (505+/
      46 vs. 803 +/- 66 ISC/10(6) cells, P < 0.001), IL-4 (2 +/- 108 vs. 641 +/- 131
      ISC/10(6) cells, P < 0.001), and IL-10 (159 +/- 105 vs. 466 +/- 407 ISC/10(6)
      cells, P < 0.002) responses. In contrast, there was no significant difference in
      cell-mediated immune response (CMI) to PHA mitogen between these two groups.
      Therefore, we concluded T cells from persons with anti-Schistosoma have reduced
      IFN-gamma, IL-4, and IL-10 secreting HCV-specific T-cell responses. This may
      explain why Schistosoma coinfection increases persistence and severity of HCV
      infection.

PMID- 15987343
TI  - Identification of karyopherin beta as an immunogenic antigen of the malaria
      parasite using immune mice and human sera.
AB  - A differential immunoscreening of the lambdagt11 Plasmodium falciparum genomic
      expression library was carried out using anti-P. yoelii sera (convalescent-phase
      mouse sera) and immune sera collected from healthy adults, to identify novel
      cross-reactive and possibly protective antigens of the parasite. One clone, with
      an insert size of 1132 bp that reacted strongly with both the sera was selected.
      The insert was found to be a part of the P. falciparum karyopherin beta (PfKbeta)
      homologue. RT-PCR and Northern blot analysis confirmed the expression of PfKbeta
      in the blood stages of the parasite. The approximately 110 kDa protein was
      localized in the cytoplasm at the ring and trophozoite, and in the
      parasitophorous vacuole at the schizont stage. Two large fragments of PfKbeta
      representing the N- and C-terminal halves were expressed in E. coli. The
      recombinant proteins were highly immunogenic in mice, and also found to be the
      target for immune response in natural infections of Plasmodium spp. Anti-sera
      against the protein showed a low level of anti-parasitic activity. Immunization
      with recombinant PfKbeta fragments was only partially protective against a
      heterologous challenge infection in mice. Our results show that the parasite
      releases a highly immunogenic, cytoplasmic protein into the host which may not
      contribute to the development of protective immunity.

PMID- 15987344
TI  - Transfusion medicine illustrated. Iatrogenic green plasma.

PMID- 15987345
TI  - Transfusion-associated adverse pulmonary sequelae: widening our perspective.

PMID- 15987346
TI  - The RADAR repository: providing a prospective perspective on the past.

PMID- 15987347
TI  - Closing the technology gap with supermarkets: implementation of ISBT 128.

PMID- 15987348
TI  - Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis
      of transfusion-associated circulatory overload.
AB  - BACKGROUND: Transfusion-associated circulatory overload (TACO) occurs when the
      transfusion rate or volume exceeds the capacity of a compromised cardiovascular
      system. Characteristic symptoms and signs associated with TACO are neither
      sensitive nor specific. B-natriuretic peptide (BNP) is a 32-amino-acid
      polypeptide secreted from the cardiac ventricles in response to ventricular
      volume expansion and pressure overload. This study was performed to explore the
      usage of BNP in the differential diagnosis of TACO. STUDY DESIGN AND METHODS: Pre
      and posttransfusion BNP levels were determined in 21 patients with suspected
      TACO and 19 control patients. The BNP was considered significant if the
      posttransfusion-to-pretransfusion ratio was at least 1.5 and the posttransfusion
      BNP level was at least 100 pg per mL. RESULTS: The BNP test has a sensitivity and
      specificity of 81 and 89 percent, respectively, in diagnosis of TACO. It has a
      positive predictive value of 89 percent, a negative predictive value of 81
      percent, and an accuracy of 87 percent. In logistic regression analysis, BNP was
      found to have significant predictive power independent of other clinical
      variables in models predicting which patients had TACO. CONCLUSIONS: Our study
      suggests that in patients who present symptoms suggestive of TACO, BNP can be a
      useful adjunct marker in confirming volume overload as the cause of acute dyspnea
      and symptoms related to cardiovascular compromise.

PMID- 15987349
TI  - A prospective randomized trial of a prophylactic platelet transfusion trigger of
      10 x 10(9) per L versus 30 x 10(9) per L in allogeneic hematopoietic progenitor
      cell transplant recipients.
AB  - BACKGROUND: The impact of lowering the platelet (PLT) count threshold for
      prophylactic PLT transfusion on bleeding and PLT use in allogeneic hematopoietic
      progenitor cell (HPC) transplant recipients is a matter of debate. STUDY DESIGN
      AND METHODS: In 166 patients, randomly assigned to receive prophylactic PLT
      transfusion at a trigger level less than 10 x 10(9) PLTs per L (T10; n = 79) or
      less than 30 x 10(9) per L (T30; n = 87), the number of PLT and red blood cell
      (RBC) transfusions given and the number of hemorrhagic events (WHO Grades 2-4)
      were recorded. RESULTS: No significant differences were found between the two
      groups regarding the clinical outcome variables (i.e., bacteremia, engraftment,
      graft-vs.-host disease [GVHD], hospital stay, death, and survival) or in the
      median total number of RBC transfusions given. The incidence, in Group T10 18
      percent (14/79) and in Group T30 15 percent (13/87), as well as the type of
      bleeding were comparable. No deaths were attributed to hemorrhages. The number of
      PLT units transfused, however, was significantly lower in Group T10 (median, 4;
      range, 0-32), than in Group T30 (median, 10; range, 0-48; p < 0.001). Apart from
      the trigger level, the day of engraftment, the presence of acute GVHD, or
      bacteremia also affected the number of PLT transfusions. CONCLUSION: A
      prophylactic PLT transfusion trigger level of less than 10 x 10(9) PLTs per L
      instead of less than 30 x 10(9) PLTs per L in allogeneic HPC transplant
      recipients was found to be safe and resulted in a decreased use of PLTs.

PMID- 15987350
TI  - The RADAR repository: a resource for studies of infectious agents and their
      transmissibility by transfusion.
AB  - BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified
      or emerging pathogens can be transmitted by transfusion. One method to study this
      question is through the use of a contemporary linked donor-recipient repository.
      STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic
      Donor and Recipient (RADAR) repository was established between 2000 and 2003 by
      seven blood centers and eight collaborating hospitals. Specimens from consented
      donors were collected, components from their donations were routed to
      participating hospitals, and recipients of these units gave enrollment and follow
      up specimens for long-term storage. The repository was designed to show that zero
      transmissions to enrolled recipients would indicate with 95 percent confidence
      that the transfusion transmission rate of an agent with prevalence of 0.05 to 1
      percent was lower than 25 percent. RESULTS: The repository contains pre- and
      posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery
      patients, linked to 13,201 donation specimens. The mean number of RADAR donation
      exposures per recipient is 3.85. The distribution of components transfused is 77
      percent red cells, 13 percent whole blood-derived platelet concentrates, and 10
      percent fresh frozen plasma. A supplementary unlinked donation repository
      containing 99,906 specimens from 84,339 donors was also established and can be
      used to evaluate the prevalence of an agent and validate assay(s) performance
      before accessing the donor-recipient-linked repository. Recipient testing
      conducted during the establishment of RADAR revealed no transmissions of human
      immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus.
      CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be
      accessed to study the transfusion transmissibility of emerging agents.

PMID- 15987351
TI  - SEN virus: epidemiology and characteristics of a transfusion-transmitted virus.
AB  - SEN virus (SEN-V) is a blood-borne, single-stranded, nonenveloped DNA virus.
      Although its prevalence varies by geographic region, it has been detected in as
      many as 30 percent of postoperative transfusion recipients, compared to 3 percent
      of postoperative patients who did not receive transfusions. A significant
      association has been observed between transfusion volume and the occurrence of
      SEN-V infection. Transmission by transfusion also has been confirmed by the
      detection of greater than 99 percent homology between SEN-V in donor and
      recipient sera. Concurrent infections with SEN-V and hepatitis B virus, hepatitis
      C virus, or human immunodeficiency virus type 1 have been documented, and these
      observations probably reflect the blood-borne transmission of these viruses as
      well as SEN-V. Although SEN-V was discovered as part of a search for causes of
      posttransfusion hepatitis, there is no firm evidence so far that SEN-V infection
      either causes hepatitis or worsens the course of coexistent liver disease.
      Nevertheless, SEN-V appears to be transmitted by transfusion, and further studies
      may reveal more about its role in the future.

PMID- 15987352
TI  - Does prevalence of transfusion-transmissible viral infection reflect
      corresponding incidence in United States blood donors?
AB  - BACKGROUND: Calculation of viral residual risk is dependent on estimating
      incidence, which is not easily obtainable by most blood centers. Prevalence,
      however, is readily available. Understanding whether prevalence reflects
      corresponding incidence may help blood centers monitor disease risks. STUDY
      DESIGN AND METHODS: With data on 12 million allogeneic donations, prevalence and
      incidence of transfusion-transmitted viral infections (TTVIs) were calculated.
      Relationships between prevalence (in total, first-time, and repeat donations) and
      incidence were analyzed for human immunodeficiency virus (HIV), hepatitis B virus
      (HBV), and hepatitis C virus (HCV) relative to temporal and donor demographic
      stratifications, respectively. RESULTS: Overall prevalence of HIV, HBV, and HCV
      did not consistently reflect corresponding incidence. The relationship between
      prevalence and incidence varied with time and donors' age and was virus-specific.
      CONCLUSION: Incidence of TTVIs cannot be easily predicted from overall
      prevalence. Accurate assessment of TTVI risk necessitates knowledge about
      donation histories and person-years at risk. Establishing comprehensive
      frameworks for monitoring blood donations and infectious disease markers remains
      a key to monitoring blood safety.

PMID- 15987353
TI  - Occurrence of hepatitis A virus genotype III in Germany requires the adaptation
      of commercially available diagnostic test systems.
AB  - BACKGROUND: A blood donation, obtained in 2003 in Germany during the
      preseroconversion diagnostic window period of a hepatitis A virus (HAV)
      infection, tested HAV-negative by commercially available HAV reverse
      transcription-polymerase chain reaction (RT-PCR) detection assays. STUDY DESIGN
      AND METHODS: The virus responsible for this infection was identified as HAV
      genotype IIIA by characterization of the nearly complete genome sequence.
      RESULTS: Thereby, this HAV variant, which was named strain HMH, was detected in
      Germany for the first time. Because the commercially available HAV RNA detection
      systems failed to detect this genotype, a real-time RT-PCR kit was developed that
      allows quantification and detection of all HAV genotypes. The first nearly full
      length nucleotide sequence so far available for HAV genotype IIIA is also
      provided. CONCLUSION: This case demonstrates that owing to the genetic
      variability of HAV, constant monitoring and adaptation of the diagnostic nucleic
      acid assays are required to guarantee the safety of blood and blood products.

PMID- 15987354
TI  - Magnetic bead technology in viral RNA and DNA extraction from plasma minipools.
AB  - BACKGROUND: Nucleic acid testing (NAT) of pooled plasma samples from individual
      blood donations for viral nucleic acids has become widely established. Full
      automation of such sample processing can overcome many of the problems associated
      with methods used so far. STUDY DESIGN AND METHODS: In this study an automated
      extraction method for viral nucleic acids (parvovirus [PAV] B19 DNA, hepatitis B
      virus [HBV] DNA, and hepatitis A virus [HAV] RNA), starting directly from the
      minipool sample (n = 96, 9.6 mL), was evaluated. A magnetic separation module I
      (chemagic, Polymer Laboratories) in combination with the chemagic viral DNA and
      RNA kit special based on the use of magnetic beads was used for this purpose.
      More than 144 pools spiked with defined concentrations of reference material and
      an additional 102 pools negative for the analyte were extracted and amplified.
      The isolated viral nucleic acids were detected by polymerase chain reaction
      (PCR). RESULTS: The assays were highly specific and obtained a 95 percent
      detection limit of 875 IU per mL of pooled single donation for PAV B19, 260 IU
      per mL for HAV, and 1274 IU per mL for HBV, respectively. The crossing points
      showed variation coefficients from 1.49 to 2.76 percent. The turnaround time for
      the whole process was 3 hours. Testing of subpools to determine an infected
      single donation would be possible with the same general extraction method. A
      total of 102 unspiked minipools (96 x 100 microL per donation) were analyzed and
      none tested positive. CONCLUSION: The automated magnetic bead-based extraction in
      combination with real-time PCR detection can be used to routinely screen blood
      donations for viremic donors to further increase the safety of blood products.
      Minipools as well as subpools can be directly processed.

PMID- 15987355
TI  - ISBT Code 128 implementation at a regional blood center.
AB  - BACKGROUND: Application specifications for ISBT 128 bar code symbology and the
      International Council for Commonality in Blood Bank Automation (ICCBBA) were
      created in 1994. By June 2000, the FDA considered ISBT 128 a standard for uniform
      labeling of blood and blood components. Our blood center initiated a change
      process for ISBT 128 implementation and "went live" in 2003. STUDY DESIGN AND
      METHODS: The intention to adopt ISBT 128 symbology with hospitals was actively
      communicated in October 2001. A Codabar-ISBT label cross-reference book was
      developed, FDA approval for the fullface label format in April 2002 was
      requested, and FDA approval was received in March 2003. In December 2002, donor
      identification labels and number sets were ordered, and an integration test plan
      was subsequently developed with departmental process flowcharts for each of the
      nine affected departments. Each step was tested, the labeling changes were
      approved in May 2003, training was completed in June 2003, and ISBT bar code
      symbology was implemented on July 1, 2003. A written survey was sent to hospital
      transfusion services in April 2004. RESULTS: Implementation went smoothly except
      for an unanticipated high rate of "no-reads" on some analyzers in the testing
      lab. The hospitals spent an average of 18 hours preparing for changes, 14 hours
      on validation, 4 hours on documentation and procedure development, and 8 hours on
      training. CONCLUSION: ISBT bar code symbology was successfully implemented.
      Hospital transfusion services made some adjustments and, overall, readily
      accepted the new bar code symbology.

PMID- 15987356
TI  - Alleviating blood shortages in a resource-constrained environment.
AB  - BACKGROUND: The nation devotes considerable resources to the collection,
      processing, and distribution of blood products. Nonetheless, shortages of
      virtually every blood component persist. Economic theory suggests that the
      national blood supply can be increased either by increasing the level of
      resources used in the collection and production of blood components or by
      utilizing existing resources more efficiently. STUDY DESIGN AND METHODS: This
      study uses data envelopment analysis to analyze the efficiency of 70 blood
      centers to determine the extent to which operational efficiency can be improved,
      the increase in the nation's blood supply that would result, and management
      strategies that would lead to such improvements. Data were collected from the
      AABB 2002-2003 Directory of Community Blood Centers. RESULTS: The study found
      that roughly half of the 70 blood centers studied are efficient. The remaining
      blood centers collectively can both increase outputs and decrease some inputs. If
      the inefficient blood centers were to eliminate half of their inefficiency, then
      systemwide output of platelets would be increased by 17 percent, cryoprecipitate
      by 12 percent, plasma by 10 percent, and red blood cells by 7 percent.
      Inefficient blood centers have little opportunity to reduce full-time employees
      or reduce expenditures; however, they can decrease their use of part-time
      employees by 10 percent and volunteers by 9 percent. CONCLUSION: The results
      indicate that efficiency improvements would help to alleviate the nation's
      persistent blood shortages. These findings can be used by blood center managers
      to identify management interventions that can improve operational efficiency,
      resulting in greater output with existing levels of resources.

PMID- 15987357
TI  - Factors affecting the formation of white particulate matter in red blood cell
      components.
AB  - BACKGROUND: Recently white particulate matter (WPM) in red blood cell (RBC)
      components has received increased attention. The nature and causes of WPM
      formation were investigated. STUDY DESIGN AND METHODS: Whole-blood units were
      collected from 18 healthy subjects with three different types of collection sets.
      Six units were collected into each type. Units were divided into four equal parts
      and stored for 4 hours: two parts at room temperature and two at 4 degrees C.
      RBCs were prepared from each quarter-unit: two by heavy centrifugation (5000 x g)
      and two by light centrifugation (2000 x g). Whole blood was inspected for WPM
      over 4 hours and RBCs over 1 hour. RESULTS: No WPM was detected in whole blood,
      but WPM was detected in at least one RBC component from 9 of the 18 donations.
      The 36 components prepared by heavy centrifugation were more likely to contain
      WPM than the 36 prepared by light centrifugation (50% vs. 19%; p < 0.02). The
      incidence of WPM was similar among RBCs stored at room temperature and 4 degrees
      C. Donors of RBCs with WPM had higher total cholesterol levels than donors of
      components without WPM (191 +/- 20 mg/dL vs. 163 +/- 32 mg/dL; p < 0.04), but
      there was no difference in triglyceride levels between the two groups.
      CONCLUSIONS: WPM is an expected consequence of standard RBC manufacturing
      methods, but it is more frequent in RBCs prepared by heavy centrifugation and
      from donors with higher cholesterol levels.

PMID- 15987358
TI  - Use of a pH meter for bacterial screening of whole blood platelets.
AB  - BACKGROUND: Bacterial contamination of blood products is a leading cause of
      transfusion-related morbidity and mortality. Transfusion services are now
      compelled to employ methods of detecting bacteria in platelet (PLT) components.
      The use of pH screening of whole-blood PLTs (WBPs) was evaluated with a pH meter
      at the time of issue as a surrogate test for bacterial contamination. STUDY
      DESIGN AND METHODS: All WBPs selected for transfusion in May through September
      2004 were tested individually for pH at time of issue. Those with a pH value of
      less than 7.0 were cultured in an automated culture system for 5 days. The white
      blood cell (WBC) and PLT counts in 56 representative WBP units that failed pH
      screening were compared to WBP units with acceptable pH values. RESULTS: Of the
      37,060 WBP units that underwent pH screening, 405 had a pH value of less than 7.0
      (1.1%). Four of those units were culture positive (1.0%) for Staphylococcus
      aureus, Bacillus subtilis, diphtheroids, and coagulase-negative Staphylococcus.
      Only one cocomponent red blood cell (RBC) unit was culture-positive and grew the
      same bacteria (S. aureus) as the WBP unit. The rate of pH failure increased with
      WBP storage length with the greatest rate of pH failures occurring in 5-day-old
      WBPs. The units that failed pH screening had significantly more WBCs and PLTs
      than units with acceptable pH values. CONCLUSION: pH screening of WBPs at issue
      prevented transfusion of bacterially contaminated WBPs and RBCs. This method,
      however, results in significant PLT wastage. Higher WBC and PLT content likely
      explains pH failures not due to bacterial contamination.

PMID- 15987359
TI  - In-house validation of the BACTEC 9240 blood culture system for detection of
      bacterial contamination in platelet concentrates.
AB  - BACKGROUND: At present, only two commercially available automated culture systems
      are cleared by the FDA for the purpose of quality control (QC) testing for
      bacterial contamination of platelet (PLT) concentrates: the BacT/ALERT blood
      culture system (bioMerieux) and the Pall eBDS (Pall Corporation), both of which
      allow testing of leukoreduced apheresis as well as whole blood-derived PLTs.
      After the decision of the AABB to institute universal QC testing of PLT
      concentrates for evidence of bacterial contamination, in-house validation of the
      performance of our current blood culture system, the BACTEC 9240, was carried out
      for this purpose. STUDY DESIGN AND METHODS: Serial dilutions of nine species of
      bacteria commonly associated with PLT contamination were prepared in one single
      donor apheresis PLT unit per organism. Four mL of dilutions containing less than
      1 to greater than 10(3) colony-forming units (CFUs) per mL was inoculated into
      blood culture bottles (Standard 10 Aerobic/F, Becton-Dickinson Diagnostic
      Systems) and incubated in a BACTEC 9240 continuously monitored blood culture
      system. Positive bottles were removed from the system and subcultured to insure
      the identity of bacterial growth. RESULTS: With the exception of Streptococcus
      mitis, the BACTEC system provided a detection sensitivity of less than 10 CFUs
      per mL for Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli,
      Serratia marcescens, Klebsiella pneumoniae, Bacillus cereus, Enterobacter
      cloacae, and Pseudomonas aeruginosa. The limit of detection for the S. mitis test
      strain was 61 CFUs per mL. Detection of positive bottles ranged from 6.5 to 17.6
      hours depending on the species tested and the cell density of the inoculum.
      Ongoing use of this system for bacterial detection yielded two true-positive
      samples from 3879 apheresis PLT products collected at our hospital-based donor
      center over 9 months. CONCLUSION: This study validates the use of the BACTEC 9240
      continuously monitored blood culture system for the detection of low-level
      bacterial contamination in single donor apheresis PLTs in less than 24 hours.

PMID- 15987360
TI  - Further evaluation of a new standard of efficacy for stored platelets.
AB  - BACKGROUND: The proposal to assess the viability capabilities of platelets (PLTs)
      collected, treated, or stored in a developmental system against "fresh" PLTs from
      the same subject poses several important methodologic issues pertaining to the
      timing and manner of the collecting and separating the fresh PLTs. This study
      extended the previous validation of this method of comparing fresh and stored
      PLTs, applying it to an assessment of apheresis PLTs stored for 7 days with a
      newly standardized radiolabeling protocol. STUDY DESIGN AND METHODS: Eighteen
      normal subjects donated 1 unit of leukoreduced PLTs, pheresed with a standard,
      approved system. They received an aliquot radiolabeled with 51Cr on Day 7
      simultaneously with 111In-labeled fresh PLTs that had been separated by a manual
      method. Recovery and survival were compared to determine whether the stored PLTs
      were not inferior to the criterion of 67 percent of recovery and 50 percent of
      survival of fresh PLTs. Separate studies were undertaken to document the
      similarity of recovery and survival with 51Cr and 111In radiolabeling in PLTs
      stored to 8 days and to determine the importance of correcting the radioactivity
      in timed samples for the activity remaining in blood beyond the life span of the
      retransfused PLTs. RESULTS: PLTs stored for 7 days demonstrated 88.7 +/- 35.2
      percent of the recovery and 89.9 +/- 21.2 percent of the survival of PLTs
      collected via a nonproprietary, manual system and thus met the comparative
      criterion. In a separate study (n = 12), labeling Day 8 PLTs with 51Cr or 111In
      resulted in recoveries and survivals that were not different. Radiolabel eluted
      from labeled PLTs in vitro was taken up by cellular blood elements in a reuptake
      incubation. CONCLUSION: Apheresis PLTs stored for 7 days met the criterion
      proposed for comparison with fresh PLTs. This analytic approach is feasible with
      PLTs collected and prepared via a manual method. A standardized protocol for
      radiolabeling PLTs with 51Cr and 111In and analyzing the results in a
      standardized fashion was employed successfully, with the two radioisotopes
      yielding similar results. The importance of correcting for residual activity
      after disappearance of injected cells was noted.

PMID- 15987361
TI  - In vitro photochemical inactivation of cell-associated human T-cell leukemia
      virus Type I and II in human platelet concentrates and plasma by use of
      amotosalen.
AB  - BACKGROUND: Human T-cell leukemia virus Types I and II (HTLV-I and HTLV-II),
      blood-borne retroviruses found worldwide, can cause leukemia, immunosuppression,
      and severe neurologic diseases. In most countries, HTLV-I and -II screening is
      not performed systematically for blood donations. A new photochemical treatment
      (PCT) with a synthetic psoralen was developed to inactivate most pathogens in
      platelet (PLT) concentrates or plasma and to improve the safety of blood
      donations. STUDY DESIGN AND METHODS: Cell-associated HTLV-I or -II (10(6)/mL) was
      inoculated in full-size fresh PLT concentrates or fresh frozen plasma and treated
      with 150 micromol per L amotosalen (S-59) and different doses of long-wavelength
      ultraviolet A (UVA) light. The residual viral titer in the treated samples was
      assessed by a cocultivation assay on indicator cells. RESULTS: The inactivation
      obtained at a 3.0 J per cm2 UVA dose was greater than 5.2 log foci-forming units
      (FFUs) per mL for HTLV-I and 4.6 log FFUs per mL for HTLV-II in presence of human
      PLT concentrates and greater than 4.5 log FFUs per mL for HTLV-I and 5.7 log FFUs
      per mL for HTLV-II in the presence of human plasma. The residual infectivity was
      very low and shown as the limit of detection of the cocultivation assay.
      CONCLUSION: In human plasma or PLT concentrates, the retroviruses HTLV-I and -II
      were strongly sensitive to the PCT with 150 micromol per L amotosalen (S-59) and
      a 3.0 J per cm2 UVA dose. This high efficiency for photoinactivation of these
      retroviruses opens a possibility of improving the safety of PLTs or plasma
      transfusion in the future.

PMID- 15987362
TI  - Purification of severe acute respiratory syndrome hyperimmune globulins for
      intravenous injection from convalescent plasma.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a new infectious disease
      caused by the SARS virus. Current first-line treatments are experimental, and
      their effectiveness remains open to question. For more effective treatment and
      prevention of SARS, human SARS hyperimmune globulins for intravenous (IV)
      injection were purified in this study. STUDY DESIGN AND METHODS: A combination of
      cold ethanol precipitation and ion-exchange chromatography was used to process
      pooled SARS convalescent plasma samples. Virus inactivation and removal
      approaches were taken to ensure safety. RESULTS: The purified hyperimmune
      globulins were formulated as a 5 percent solution, with an antibody titer
      specifically against the SARS virus of 1:83, 1:1600, and 1:200, as determined by
      enzyme-linked immunosorbent assay, immunofluorescence assay, and neutralizing
      antibody test, respectively. The purity of the SARS hyperimmune globulins was
      99.0 percent, and the monomer and dimer content was 100 percent. Other variables
      analyzed met the Chinese Requirements of Biologics for IV immune globulin. The
      SARS hyperimmune globulins prepared were subsequently approved for clinical
      evaluation by the Chinese National Institute for the Control of Pharmaceutical &
      Biological Products. CONCLUSION: IV-injectable, purified, and concentrated human
      SARS hyperimmune globulins were prepared from pooled convalescent plasma samples,
      which are ready to be further evaluated.

PMID- 15987363
TI  - Characterization of the alloreactive helper T-cell response to the platelet
      membrane glycoprotein IIIa (integrin-beta3) in human platelet antigen-1a
      alloimmunized human platelet antigen-1b1b women.
AB  - BACKGROUND: The aims were to characterize the helper T-cell response to platelet
      (PLT) glycoprotein (GP) IIIa, which stimulates the alloimmune antibody response
      to human PLT antigen (HPA)-1a, to identify immunodominant epitopes and to examine
      the HLA Class II associations. STUDY DESIGN AND METHODS: Peripheral blood
      mononuclear cells (PBMNCs) were obtained from 21 HPA-1b1b women who had an HPA-1a
      mismatched pregnancy, 14 of whom developed anti-HPA-1a, and 11 control donors.
      PBMNCs were stimulated with two panels of 15-mer peptides corresponding to the
      HPA-1a/1b polymorphic region, with either Leu33 (-1a) or Pro33 (-1b) at each
      possible position, and the proliferative responses were measured. HLA Class II
      and HPA genotyping was by conventional polymerase chain reaction-sequence
      specific priming. RESULTS: Peptides with Leu33 at, or near, the C-terminus
      contained an immunodominant epitope, stimulating proliferation by helper T cells
      from all nine women who had anti-HPA-1a at the time of testing; peptide L1 (Val19
      Leu33) stimulated a response in 50 percent of these women. Their T cells did not
      respond to the corresponding HPA-1b Pro33 peptides, and responses to either
      peptide panel were rare in unimmunized women and controls. HLA-DRB3*01+ was
      significantly overrepresented (p = 0.014) in alloimmunized women whose T cells
      responded to the major HPA-1a Leu33-containing epitope. Conversely, HLA-DRB1*15
      was negatively associated (p = 0.014) with this response. CONCLUSIONS: The HPA-1a
      polymorphic region of GPIIIa contains both the linear T-cell and the
      conformational B-cell epitopes. The immunodominant T-cell epitope is constrained
      by HLA-DRB3*01+, and if presented by a tolerogenic route, a peptide containing
      this epitope may form the basis for the prevention or reversal of the alloimmune
      response to HPA-1a.

PMID- 15987365
TI  - Random survey for RHD alleles among D+ European persons.
AB  - BACKGROUND: RHD alleles are considered more variable in African persons than in
      European persons. A systematic survey, however, was lacking among D+ European
      persons at the molecular level, precluding any definite frequency estimate. STUDY
      DESIGN AND METHODS: A random survey was performed among 500 ccDee, 250 CcDee, and
      250 ccDEe blood donors in southwestern Germany. They were tested by polymerase
      chain reaction with sequence-specific priming (PCR-SSP) for up to 12 single
      nucleotide polymorphisms representative for the most frequent RHD alleles among
      European persons. The RHD exon 5 nucleotide sequence was also tested in all 1000
      samples. The nucleotide sequence of the 10 RHD exons was checked in all samples
      with aberrant exon 5 or positive PCR-SSP procedures. RESULTS: By PCR-SSP, 15
      aberrant RHD alleles were found among the 500 ccDee, 2 among the 250 CcDee, and
      none among the ccDEe samples. One of these was the novel RHD(F223V, E233Q, T379M)
      allele dubbed DAU-5. Weak D type 4 was detected more frequently than expected,
      whereas the population frequencies of the other RHD alleles conformed to
      published estimates. Nucleotide sequencing of RHD exon 5 further revealed three
      novel alleles RHD(G212G), RHD(R234W), and RHD(V245L), dubbed DUC-1, DQC, and DUC
      2. CONCLUSION: In a limited screen at the molecular level among 1000 random D+
      donors in southwestern Germany, 20 donors were found carrying aberrant RHD
      alleles. Four of these alleles were new and likely sporadic. An estimate was
      derived of the variety that may be encountered in genotyping approaches, and it
      was concluded that even within the European population the variety of RHD alleles
      may be larger than anticipated.

PMID- 15987364
TI  - Amino-acid substitution in the disordered loop of blood group B
      glycosyltransferase enzyme causes weak B phenotype.
AB  - BACKGROUND: Few studies have investigated the reaction kinetics and interactions
      with nucleotide donor and acceptor substrates of mutant human ABO
      glycosyltransferases. Previous work identified a B(w) allele featuring a 556G>A
      polymorphism giving rise to a weak B phenotype. This polymorphism is predicted to
      cause a M186V amino-acid mutation within a highly conserved series of 16 amino
      acids present both in both blood group A- and blood group B-synthesizing enzymes.
      These residues are known as the disordered loop because their location cannot be
      determined in the crystal structure of the enzyme. Another patient has been
      identified with a 556G>A B(w) allele and the kinetics of the resulting mutant
      glycosyltransferase were studied. STUDY DESIGN AND METHODS: Serologic testing
      with murine and human reagents, amplification of the coding regions of exons 6
      and 7, and DNA sequencing were performed with standard protocols. Enzyme kinetic
      studies utilized a model of human GTB M186V expressed in Escherichia coli with
      radiolabeled UDP-galactose and UDP-N-acetylgalactosamine as donor substrates and
      synthetic H-disaccharide as acceptor following standard protocols. RESULTS: The
      patient's red blood cells demonstrated a weak, but not mixed-field, B phenotype.
      Kinetic studies on the mutant enzyme revealed diminished activity (k(cat) = 0.15
      per sec with UDP-galactose compared to 5.1 per sec for wild-type GTB) and
      elevated K(m) values for all substrates. CONCLUSION: This enzyme with a mutation
      in the disordered loop produces weak B antigen expression because of greatly
      decreased enzyme activity and reduced affinity for B-donor and acceptor
      substances.

PMID- 15987366
TI  - The alpha4beta1 and alpha5beta1 integrins mediate engraftment of granulocyte
      colony-stimulating factor-mobilized human hematopoietic progenitor cells.
AB  - BACKGROUND: The alpha4beta1 and alpha5beta1 integrins are major adhesion
      molecules of murine and human hematopoietic progenitor cells. Granulocyte-colony
      stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs)
      are the most important source for clinical hematopoietic cell transplantation
      today. The contribution of alpha4beta1 and alpha5beta1 integrins to homing of
      PBPCs has not been studied yet. STUDY DESIGN AND METHODS: The expression of
      alpha4beta1 and alpha5beta1 integrins on purified human PBPCs was analyzed.
      Integrin function in adhesion to recombinant fibronectin and migration on
      fibronectin-coated transwells was assessed with fragments combining different
      adhesion domains and function-blocking antibodies. Finally, the function of those
      integrins in a transplantation model was investigated with repopulating cells of
      nonobese diabetic/severe combined immune-deficient (NOD/SCID) mice. RESULTS: More
      than 90 percent of all purified peripheral blood CD34+ cells express alpha4beta1
      integrins, whereas only 10 to 15 percent express alpha5beta1. The alpha4beta1
      integrin alone influences adhesion whereas alpha4beta1 and alpha5beta1 both
      mediate chemotaxis of clonogenic CD34+ progenitor cells on recombinant
      fibronectin. Importantly, antibodies against the integrins alpha4beta1 and
      alpha5beta1 independently reduce the repopulation of NOD/SCID mouse marrow after
      transplantation of human peripheral blood CD34+ cells. CONCLUSIONS: Alpha4beta1
      and alpha5beta1 integrins are functional and critical adhesion receptors
      expressed on G-CSF-mobilized CD34+ hematopoietic blood progenitor cells with
      repopulating capacity mediating engraftment after transplantation.

PMID- 15987367
TI  - Toward closed-system culture of blood origin endothelial cells.
AB  - BACKGROUND: Blood outgrowth endothelial cells (BOECs) are thought to arise from
      very rare progenitors that are present in the mononuclear fraction of marrow or
      peripheral blood. Recently, BOECs have been expanded from progenitors present in
      buffy coat into confluent monolayers on fibronectin- or collagen-coated
      polystyrene surfaces. A method for sterile closed-system culture of these cells
      has not been described, however. Here, efforts are described toward developing
      closed-system culture of BOECs derived from progenitors present in a mononuclear
      apheresis unit by use of a cord blood filter, a sterile connection device, and a
      fibronectin-coated polycarbonate cassette. STUDY DESIGN AND METHODS: Strongly
      adherent cells from a mononuclear apheresis unit were eluted from a cord blood
      filter and resuspended in EGM-2 with 10 percent serum. Approximately 2 x 10(8)
      eluted cells were introduced into human fibronectin-coated polycarbonate
      cassettes. Medium was introduced and removed from cassettes with a sterile
      connection device and changed every 2 days. After expansion, cells were either
      cryopreserved or characterized by fluorescence-activated cell sorting analysis
      and ability to take up Dil-Ac-LDL. RESULTS: After 2 to 3 weeks of culture, 3 to
      28 colonies with cobblestone morphology were observed in cassettes and passed to
      new cassettes within 3 to 4 weeks. By approximately 5 weeks of culture, 2 x 10(6)
      cells were typically obtained. BOECs uniformly took up Dil-Ac-LDL and were CD31+,
      CD105+, CD146+, CD45-, and CD14-. A population of BOECs was HLA-ABC+ or CD34+.
      CONCLUSION: BOEC progenitors can be isolated from mononuclear apheresis units
      with cord blood filters, expanded with fibronectin-coated polycarbonate
      cassettes, and cryopreserved.

PMID- 15987368
TI  - Establishment and optimization of a flow cytometric method for evaluation of
      viability of CD34+ cells after cryopreservation and comparison with trypan blue
      exclusion staining.
AB  - BACKGROUND: Trypan blue exclusion staining is probably the most frequently
      applied method (Method I) for assessment of viability in peripheral blood
      progenitor cell grafts after cryopreservation. Alternatively, a flow cytometry
      based method (Method II) was established and optimized. STUDY DESIGN AND METHODS:
      In a first series of 22 autologous apheresis products, the influence of duration
      of antibody staining and red cell (RBC) lysis on viability was investigated. In a
      second series of 21 autologous and 1 allogeneic apheresis products, the effect of
      omitting the RBC lysis was evaluated. On the basis of the results of the first
      two series, 155 autologous and 57 allogeneic apheresis products were analyzed
      with Method I and the now optimized Method II. RESULTS: Halving the incubation
      times did not influence the viability of CD45+ or CD34+ cells. Omission of RBC
      lysis resulted in a significantly (p = 0.022) increased median viability of CD45+
      cells (75.8% vs. 71.0%) without any influence on CD34+ cells. In the third
      series, the median viability of CD34+ cells (96.9%) was significantly (p <
      0.0001) higher compared with the viability of CD45+ cells (76.2%) and the
      viability determined by Method I (86.5%). CONCLUSION: The viability of CD34+
      cells was significantly higher compared with the viability of all white blood
      cells. The presented cytometry-based method is superior to the standard trypan
      blue method regarding the number of analyzable cells and documentation, regarding
      observer independence and standardization; it allows the analysis of the cells of
      interest for transplantation after minimal sample manipulation.

PMID- 15987369
TI  - Peripheral blood progenitor cell collection in chronic myeloid leukemia patients
      with complete cytogenetic response after treatment with imatinib mesylate.
AB  - BACKGROUND: Imatinib mesylate (IM) was introduced in chronic myeloid leukemia
      (CML) treatment in the late 1990s and substantially changed the therapeutic
      approach to the disease, by inducing complete cytogenetic response (CCR) in
      approximately 60 percent of cases. Nevertheless, some concerns exist about the
      duration of response to treatment and the onset of resistance to IM. STUDY DESIGN
      AND METHODS: Twenty-five chronic-phase CML patients in stable CCR (>6 months)
      treated for at least 1 year with IM at the standard dose (400 mg/day) were
      mobilized with recombinant human granulocyte-colony-stimulating factor
      (Filgrastim) at 10 microg per kg for 4 to 6 days, with the aim of collecting at
      least 2 x 10(6) CD34+ cells per kg. Standard cytogenetic analysis and first-round
      and/or nested polymerase chain reaction were performed in basal and
      postmobilization samples to examine the presence of bcr-abl transcripts. RESULTS:
      CD34+ cells collection was successful in 16 patients, yielding a median of 3.01 x
      10(6) +/- 1.09 x 10(6) CD34+ cells per kg at the first attempt, and in 4 of the 9
      remaining patients who were remobilized after a temporary withdrawal of IM,
      yielding a median of 2.65 x 10(6) +/- 0.7 x 10(6) CD34+ cells per kg, with an
      overall 80 percent success rate. No correlation between mobilization and duration
      of the disease, length of IM treatment, or previous interferon-alpha and/or
      hydroxyurea treatment was found. CONCLUSIONS: Autologous CD34+ cells may be
      mobilized and collected in most CML patients who achieve CCR after IM treatment,
      with a view to possible use in the event that resistance to IM occurs in patients
      not eligible for allogeneic peripheral blood progenitor cell transplantation or
      those lacking an HLA-matched donor.

PMID- 15987370
TI  - Hemostatic effects of fibrinogen gamma-chain dodecapeptide-conjugated polymerized
      albumin particles in vitro and in vivo.
AB  - BACKGROUND: Prototypes of platelet (PLT) substitutes have been studied and the
      focus was on a dodecapeptide, HHLGGAKQAGDV (H12), which is a fibrinogen gamma
      chain carboxy-terminal sequence (gamma 400-411) and exists only in the fibrinogen
      domain. STUDY DESIGN AND METHODS: H12 was conjugated to the surface of
      polymerized albumin particles (polyAlb) as biocompatible and biodegradable
      particles with a mean diameter of 260 +/- 60 nm, and the hemostatic ability of
      H12-conjugated polyAlb (H12-polyAlb) under flow conditions and thrombocytopenic
      rats have been studied. RESULTS: H12-polyAlb enhanced the in vitro thrombus
      formation of activated PLTs on a collagen-immobilized plate when exposed to the
      flowing thrombocytopenic imitation blood. Furthermore, the analysis of the tail
      bleeding time of rats that were made thrombocytopenic by busulfan injection
      showed that H12-polyAlb had a hemostatic effect. Based on the bleeding time and
      the amount injected, the hemostatic capacity of 20 H12-polyAlb was estimated to
      correspond to that of one PLT. CONCLUSION: These results were important first
      steps toward the development of PLT substitutes and indicated that H12-polyAlb
      may be a suitable candidate for an alternative to human PLT concentrates
      transfused into thrombocytopenic patients in the future.

PMID- 15987371
TI  - Signaled expression of fetal hemoglobin during development.

PMID- 15987373
TI  - Fresh frozen plasma is ineffective for correcting minimally elevated
      international normalized ratios.

PMID- 15987375
TI  - Independent association of massive blood loss with mortality in cardiac surgery.

PMID- 15987376
TI  - Compensating for iron loss in regular blood donors using ferrous gluconate and
      ascorbic acid.

PMID- 15987377
TI  - Comparison of computerized formulae for determination of platelet recovery and
      survival.

PMID- 15987380
TI  - Bench-to-bedside review: Therapeutic options and issues in the management of
      ventilator-associated bacterial pneumonia.
AB  - Despite progress in the diagnosis, prevention and therapy for hospital-acquired
      infections, ventilator-associated pneumonia (VAP) continues to complicate the
      course of a significant proportion of patients receiving mechanical ventilation.
      Mortality rates among patients with VAP have been reported to be as high as 72%,
      and the morbidity associated with VAP is also considerable, adding days to the
      hospital stay and increasing health care costs. Appropriate initial antimicrobial
      therapy for patients with VAP has been shown to reduce mortality rates and
      improve outcomes; therefore, rapid identification of infected patients and
      timely, accurate selection of effective antimicrobial agents are important
      clinical goals. The primary organisms responsible for VAP include
      Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. However,
      aetiologies differ considerably between intensive care units, and the increase in
      antibiotic resistance and nosocomial outbreaks worldwide have presented
      clinicians with a serious dilemma with respect to selecting appropriate empirical
      therapy. To date, no optimal antimicrobial regimen for the treatment of VAP has
      been identified, largely because none of the currently marketed antibiotics has a
      sufficiently extended spectrum of activity to cover all of the potential key
      pathogens. More active, less toxic antibacterial agents are still needed, in
      particular to combat problematic pathogens such as multiresistant Gram-negative
      bacilli and resistant Gram-positive organisms (e.g. methicillin-resistant S
      aureus).

PMID- 15987382
TI  - Clinical review: Devices and drugs for cardiopulmonary resuscitation --
      opportunities and restraints.
AB  - The science and technology of CPR is only just emerging from its infancy.
      However, substantial improvements are anticipated, including the ability of lay
      rescuers to identify cardiac arrest promptly, the availability of additional
      measurements, and expanded intelligence provided by expanded AEDs with which to
      more effectively prompt the rescuer through the resuscitation procedure. Most
      important in our view is the ability to maintain uninterrupted precordial
      compression. Better timing and better waveforms for defibrillation are emerging.
      The recognition of the importance of postresuscitation myocardial dysfunction and
      the selection of better vasopressor agents to minimize the adverse inotropic and
      chronotropic actions of adrenergic drugs are also likely to improve outcomes of
      CPR.

PMID- 15987381
TI  - Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery -- a
      systematic literature review.
AB  - Many adult patients require temporary inotropic support after cardiac surgery. We
      reviewed the literature systematically to establish, present and classify the
      evidence regarding choice of inotropic drugs. The available evidence, while
      limited in quality and scope, supports the following observations; although all
      beta-agonists can increase cardiac output, the best studied beta-agonist and the
      one with the most favourable side-effect profile appears to be dobutamine.
      Dobutamine and phosphodiesterase inhibitors (PDIs) are efficacious inotropic
      drugs for management of the low cardiac output syndrome. Dobutamine is associated
      with a greater incidence of tachycardia and tachyarrhythmias, whereas PDIs often
      require the administration of vasoconstrictors. Other catecholamines have no
      clear advantages over dobutamine. PDIs increase the likelihood of successful
      weaning from cardiopulmonary bypass as compared with placebo. There is
      insufficient evidence that inotropic drugs should be selected for their effects
      on regional perfusion. PDIs also increase flow through arterial grafts, reduce
      mean pulmonary artery pressure and improve right heart performance in pulmonary
      hypertension. Insufficient data exist to allow selection of a specific inotropic
      agent in preference over another in adult cardiac surgery patients. Multicentre
      randomized controlled trials focusing on clinical rather than physiological
      outcomes are needed.

PMID- 15987383
TI  - Clinical review: Emergency department overcrowding and the potential impact on
      the critically ill.
AB  - Critical care constitutes a significant and growing proportion of the practice of
      emergency medicine. Emergency department (ED) overcrowding in the USA represents
      an emerging threat to patient safety and could have a significant impact on the
      critically ill. This review describes the causes and effects of ED overcrowding;
      explores the potential impact that ED overcrowding has on care of the critically
      ill ED patient; and identifies possible solutions, focusing on ED based critical
      care.

PMID- 15987387
TI  - Erythropoietin response in critically ill mechanically ventilated patients: a
      prospective observational study.
AB  - INTRODUCTION: Anemia is a common problem in critically ill patients. The etiology
      of anemia of critical illness is often determined to be multifactorial in the
      clinical setting, but the pathophysiology remains to be elucidated.
      Erythropoietin (EPO) is an endogenous glycoprotein hormone that serves as the
      primary stimulus for erythropoiesis. Recent evidence has demonstrated a blunted
      EPO response as a factor contributing to anemia of critical illness in specific
      subsets of patients. Critically ill patients requiring mechanical ventilation who
      exhibit anemia have not been the subject of previous studies. Our goal was to
      evaluate the erythropoietic response to anemia in the critically ill mechanically
      ventilated patient. METHODS: A prospective observational study was undertaken in
      the medical intensive care unit of a tertiary care, military hospital. Twenty
      patients admitted to the medical intensive care unit requiring mechanical
      ventilation for at least 72 hours were enrolled as study patients. EPO levels and
      complete blood count were measured 72 hours after admission and initiation of
      mechanical ventilation. Admission clinical and demographic data were recorded,
      and patients were followed for the duration of mechanical ventilation. Twenty
      patients diagnosed with iron deficiency anemia in the outpatient setting were
      enrolled as a control population. Control patients had baseline complete blood
      count and iron panel recorded by primary care physicians. EPO levels were
      measured at the time of enrollment in conjunction with complete blood count.
      RESULTS: The mean EPO level for the control population was 60.9 mU/ml. The mean
      EPO level in the mechanically ventilated patient group was 28.7 mU/ml, which was
      significantly less than in the control group (P = 0.035). The mean hemoglobin
      value was not significantly different between groups (10.6 g/dl in mechanically
      ventilated patients versus 10.2 g/dl in control patients; P > 0.05). CONCLUSION:
      Mechanically ventilated patients demonstrate a blunted EPO response to anemia.
      Further study of therapies directed at treating anemia of critical illness and
      evaluating its potential impact on mechanical ventilation outcomes and mortality
      is warranted.

PMID- 15987384
TI  - Clinical review: New technologies -- venturing out of the intensive care unit.
AB  - The delivery of critical care is no longer limited to the intensive care unit.
      The information gained by utilization of new technologies has proven beneficial
      in some populations. Research into earlier and more widespread use of these
      modalities may prove to be of even greater benefit to critically ill patients.

PMID- 15987388
TI  - Outcome and prognostic factors in critically ill patients with systemic lupus
      erythematosus: a retrospective study.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an archetypal autoimmune
      disease, involving multiple organ systems with varying course and prognosis.
      However, there is a paucity of clinical data regarding prognostic factors in SLE
      patients admitted to the intensive care unit (ICU). METHODS: From January 1992 to
      December 2000, all patients admitted to the ICU with a diagnosis of SLE were
      included. Patients were excluded if the diagnosis of SLE was established at or
      after ICU admission. A multivariate logistic regression model was applied using
      Acute Physiology and Chronic Health Evaluation II scores and variables that were
      at least moderately associated (P < 0.2) with survival in the univariate
      analysis. RESULTS: A total of 51 patients meeting the criteria were included. The
      mortality rate was 47%. The most common cause of admission was pneumonia with
      acute respiratory distress syndrome. Multivariate logistic regression analysis
      showed that intracranial haemorrhage occurring while the patient was in the ICU
      (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk =
      6.97) and concurrent septic shock (relative risk = 77.06) were associated with
      greater risk of dying, whereas causes of ICU admission and Acute Physiology and
      Chronic Health Evaluation II score were not significantly associated with death.
      CONCLUSION: The mortality rate in critically ill SLE patients was high.
      Gastrointestinal bleeding, intracranial haemorrhage and septic shock were
      significant prognostic factors in SLE patients admitted to the ICU.

PMID- 15987389
TI  - The effect of activated protein C on experimental acute necrotizing pancreatitis.
AB  - INTRODUCTION: Acute pancreatitis is a local inflammatory process that leads to a
      systemic inflammatory response in the majority of cases. Bacterial contamination
      has been estimated to occur in 30-40% of patients with necrotizing pancreatitis.
      Development of pancreatic necrosis depends mainly on the degree of inflammation
      and on the microvascular circulation of the pancreatic tissue. Activated protein
      C (APC) is known to inhibit coagulation and inflammation, and to promote
      fibrinolysis in patients with severe sepsis. We investigated the effects of APC
      on histopathology, bacterial translocation, and systemic inflammation in
      experimental acute necrotizing pancreatitis. MATERIALS AND METHOD: Forty-five
      male Sprague-Dawley rats were studied. Rats were randomly allocated to three
      groups. Acute pancreatitis was induced in group II (positive control; n = 15) and
      group III (treatment; n = 15) rats by retrograde injection of taurocholate into
      the common biliopancreatic duct. Group I rats (sham; n = 15) received an
      injection of normal saline into the common biliopancreatic duct to mimic a
      pressure effect. Group III rats were treated with intravenous APC 6 hours after
      induction of pancreatitis. Pancreatic tissue and blood samples were obtained from
      all animals for histopathological examination and assessment of amylase, tumor
      necrosis factor-alpha, and IL-6 levels in serum. Bacterial translocation to
      pancreas and mesenteric lymph nodes was measured. RESULTS: Acute pancreatitis
      developed in all groups apart from group I (sham), as indicated by microscopic
      parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid.
      Histopathological pancreatitis scores in the APC-treated group were lower than in
      positive controls (10.31 +/- 0.47 versus 14.00 +/- 0.52; P < 0.001). Bacterial
      translocation to mesenteric lymph nodes and to pancreas in the APC-treated group
      was significantly decreased compared with controls (P < 0.02 and P < 0.007,
      respectively). Serum amylase, tumor necrosis factor-alpha, and IL-6 levels were
      also significantly decreased in comparison with positive controls (P < 0.001, P <
      0.04 and P < 0.001, respectively). CONCLUSION: APC improved the severity of
      pancreatic tissue histology, superinfection rates and serum markers of
      inflammation during the course of acute necrotizing pancreatitis.

PMID- 15987390
TI  - Isolation of Aspergillus spp. from the respiratory tract in critically ill
      patients: risk factors, clinical presentation and outcome.
AB  - INTRODUCTION: Our aims were to assess risk factors, clinical features, management
      and outcomes in critically ill patients in whom Aspergillus spp. were isolated
      from respiratory secretions, using a database from a study designed to assess
      fungal infections. METHODS: A multicentre prospective study was conducted over a
      9-month period in 73 intensive care units (ICUs) and included patients with an
      ICU stay longer than 7 days. Tracheal aspirate and urine samples, and
      oropharyngeal and gastric swabs were collected and cultured each week. On
      admission to the ICU and at the initiation of antifungal therapy, the severity of
      illness was evaluated using the Acute Physiology and Chronic Health Evaluation II
      score. Retrospectively, isolation of Aspergillus spp. was considered to reflect
      colonization if the patient did not fulfil criteria for pneumonia, and infection
      if the patient met criteria for pulmonary infection and if the clinician in
      charge considered the isolation to be clinically valuable. Risk factors,
      antifungal use and duration of therapy were noted. RESULTS: Out of a total of
      1756 patients, Aspergillus spp. were recovered in 36. Treatment with steroids
      (odds ratio = 4.5) and chronic obstructive pulmonary disease (odds ratio = 2.9)
      were significantly associated with Aspergillus spp. isolation in multivariate
      analysis. In 14 patients isolation of Aspergillus spp. was interpreted as
      colonization, in 20 it was interpreted as invasive aspergillosis, and two cases
      were not classified. The mortality rates were 50% in the colonization group and
      80% in the invasive infection group. Autopsy was performed in five patients with
      clinically suspected infection and confirmed the diagnosis in all of these cases.
      CONCLUSION: In critically ill patients, treatment should be considered if
      features of pulmonary infection are present and Aspergillus spp. are isolated
      from respiratory secretions.

PMID- 15987391
TI  - Decreased duration of mechanical ventilation when comparing analgesia-based
      sedation using remifentanil with standard hypnotic-based sedation for up to 10
      days in intensive care unit patients: a randomised trial [ISRCTN47583497].
AB  - INTRODUCTION: This randomised, open-label, multicentre study compared the safety
      and efficacy of an analgesia-based sedation regime using remifentanil with a
      conventional hypnotic-based sedation regime in critically ill patients requiring
      prolonged mechanical ventilation for up to 10 days. METHODS: One hundred and five
      randomised patients received either a remifentanil-based sedation regime (initial
      dose 6 to 9 microg kg(-1) h(-1) (0.1 to 0.15 microg kg(-1) min(-1)) titrated to
      response before the addition of midazolam for further sedation (n = 57), or a
      midazolam-based sedation regime with fentanyl or morphine added for analgesia (n
      = 48). Patients were sedated to an optimal Sedation-Agitation Scale (SAS) score
      of 3 or 4 and a pain intensity (PI) score of 1 or 2. RESULTS: The remifentanil
      based sedation regime significantly reduced the duration of mechanical
      ventilation by more than 2 days (53.5 hours, P = 0.033), and significantly
      reduced the time from the start of the weaning process to extubation by more than
      1 day (26.6 hours, P < 0.001). There was a trend towards shortening the stay in
      the intensive care unit (ICU) by 1 day. The median time of optimal SAS and PI was
      the same in both groups. There was a significant difference in the median time to
      offset of pharmacodynamic effects when discontinuing study medication in patients
      not extubated at 10 days (remifentanil 0.250 hour, comparator 1.167 hours; P <
      0.001). Of the patients treated with remifentanil, 26% did not receive any
      midazolam during the study. In those patients that did receive midazolam, the use
      of remifentanil considerably reduced the total dose of midazolam required.
      Between days 3 and 10 the weighted mean infusion rate of remifentanil remained
      constant with no evidence of accumulation or of a development of tolerance to
      remifentanil. There was no difference between the groups in SAS or PI score in
      the 24 hours after stopping the study medication. Remifentanil was well
      tolerated. CONCLUSION: Analgesia-based sedation with remifentanil was well
      tolerated; it reduces the duration of mechanical ventilation and improves the
      weaning process compared with standard hypnotic-based sedation regimes in ICU
      patients requiring long-term ventilation for up to 10 days.

PMID- 15987392
TI  - Tezosentan-induced attenuation of lung injury in endotoxemic sheep is associated
      with reduced activation of protein kinase C.
AB  - INTRODUCTION: Studies in vitro reveal that endothelin-1 (ET-1) activates the
      alpha isoform of protein kinase C (PKC-alpha) in cultures of endothelial cells,
      thereby deranging cellular integrity. Sepsis and endotoxemia are associated with
      increased plasma concentrations of ET-1 that induce acute lung injury (ALI). We
      recently reported that non-selective ET-1 receptor blockade attenuates ALI in
      sheep by reducing the endotoxin-induced increase in extravascular lung water
      index (EVLWI). The aim of this study was to find out whether this attenuation is
      associated with reduced translocation of PKC-alpha from the cytosolic to the
      membrane fraction of lung tissue homogenate. METHODS: Seventeen awake,
      instrumented sheep were randomly assigned to a sham-operated group (n = 3), a
      lipopolysaccharide (LPS) group (n = 7) receiving an intravenous infusion of
      Escherichia coli 15 ng/kg per min for 24 hours, and a tezosentan group (n = 7)
      subjected to LPS and, from 4 hours, an intravenous injection of tezosentan 3
      mg/kg followed by infusion at 1 mg/kg per hour for the reminder of the
      experiment. Pulmonary micro-occlusion pressure (Pmo), EVLWI, plasma
      concentrations of ET-1, tumor necrosis factor-a (TNF-a), and interleukin-8 (IL-8)
      were determined every 4 hours. Western blotting was used to assess PKC-alpha.
      RESULTS: In non-treated sheep a positive correlation was found between the plasma
      concentration of ET-1 and Pmo in the late phase of endotoxemia (12 to 24 hours).
      A positive correlation was also noticed between Pmo and EVLWI in the LPS and the
      LPS plus tezosentan groups, although the latter was significantly reduced in
      comparison with LPS alone. In both endotoxemic groups, plasma concentrations of
      ET-1, TNF-alpha, and IL-8 increased. In the LPS group, the cytosolic fraction of
      PKC-alpha decreased by 75% whereas the membrane fraction increased by 40% in
      comparison with the sham-operated animals. Tezosentan completely prevented the
      changes in PKC-alpha in both the cytosolic and the membrane fractions,
      concomitantly causing a further increase in the plasma concentrations of ET-1,
      TNF-alpha, and IL-8. CONCLUSION: In endotoxemic sheep, ET-1 receptor blockade
      alleviates lung injury as assessed by a decrease in EVLWI paralleled by a
      reduction in Pmo and the prevention of activation of PKC-alpha.

PMID- 15987393
TI  - Daily enteral feeding practice on the ICU: attainment of goals and interfering
      factors.
AB  - BACKGROUND: The purpose of this study was to evaluate the daily feeding practice
      of enterally fed patients in an intensive care unit (ICU) and to study the impact
      of preset factors in reaching predefined optimal nutritional goals. METHODS: The
      feeding practice of all ICU patients receiving enteral nutrition for at least 48
      hours was recorded during a 1-year period. Actual intake was expressed as the
      percentage of the prescribed volume of formula (a success is defined as 90% or
      more). Prescribed volume (optimal intake) was guided by protocol but adjusted to
      individual patient conditions by the intensivist. The potential barriers to the
      success of feeding were assessed by multivariate analysis. RESULTS: Four-hundred
      and-three eligible patients had a total of 3,526 records of feeding days. The
      desired intake was successful in 52% (1,842 of 3,526) of feeding days. The
      percentage of successful feeding days increased from 39% (124 of 316) on day 1 to
      51% (112 of 218) on day 5. Average ideal protein intake was 54% (95% confidence
      interval (CI) 52 to 55), energy intake was 66% (95% CI 65 to 68) and volume 75%
      (95% CI 74 to 76). Factors impeding successful nutrition were the use of the
      feeding tube to deliver contrast, the need for prokinetic drugs, a high
      Therapeutic Intervention Score System category and elective admissions.
      CONCLUSION: The records revealed an unsatisfactory feeding process. A better use
      of relative successful volume intake, namely increasing the energy and protein
      density, could enhance the nutritional yield. Factors such as an improper use of
      tubes and feeding intolerance were related to failure. Meticulous recording of
      intake and interfering factors helps to uncover inadequacies in ICU feeding
      practice.

PMID- 15987394
TI  - Continuously assessed right ventricular end-diastolic volume as a marker of
      cardiac preload and fluid responsiveness in mechanically ventilated cardiac
      surgical patients.
AB  - INTRODUCTION: Assessing cardiac preload and fluid responsiveness accurately is
      important when attempting to avoid unnecessary volume replacement in the
      critically ill patient, which is associated with increased morbidity and
      mortality. The present clinical trial was designed to compare the reliability of
      continuous right ventricular end-diastolic volume (CEDV) index assessment based
      on rapid response thermistor technique, cardiac filling pressures (central venous
      pressure [CVP] and pulmonary capillary wedge pressure [PCWP]), and
      transesophageal echocardiographically derived evaluation of left ventricular end
      diastolic area (LVEDA) index in predicting the hemodynamic response to volume
      replacement. METHODS: We studied 21 patients undergoing elective coronary artery
      bypass grafting. After induction of anesthesia, hemodynamic parameters were
      measured simultaneously before (T1) and 12 min after volume replacement (T2) by
      infusion of 6% hydroxyethyl starch 200/0.5 (7 ml/kg) at a rate of 1 ml/kg per
      min. RESULTS: The volume-induced increase in thermodilution-derived stroke volume
      index (SVITD) was 10% or greater in 19 patients and under 10% in two. There was a
      significant correlation between changes in CEDV index and changes in SVITD (r2 =
      0.55; P < 0.01), but there were no significant correlations between changes in
      CVP, PCWP and LVEDA index, and changes in SVITD. The only variable apparently
      indicating fluid responsiveness was LVEDA index, the baseline value of which was
      weakly correlated with percentage change in SVITD (r2 = 0.38; P < 0.01).
      CONCLUSION: An increased cardiac preload is more reliably reflected by CEDV index
      than by CVP, PCWP, or LVEDA index in this setting of preoperative cardiac
      surgery, but CEDV index did not reflect fluid responsiveness. The response of
      SVITD following fluid administration was better predicted by LVEDA index than by
      CEDV index, CVP, or PCWP.

PMID- 15987395
TI  - Does fluid loading influence measurements of intestinal permeability?
AB  - INTRODUCTION: Urinary recovery of enterally administered probes is used as a
      clinical test of intestinal mucosal permeability. Recently, evidence has been
      provided that the recovery of some but not all sugar probes is dependent on the
      amount of diuresis and renal function. The aim of this study was to assess the
      effect of fluid loading on the urinary recovery of sugar probes in healthy
      volunteers. METHODS: In a cross-over study, 10 healthy volunteers ingested 100 ml
      of a solution containing 0.2 g of 3-O-methyl-D-glucose (3-OMG), 0.5 g of D
      xylose, 1.0 g of L-rhamnose, and 5.0 g of lactulose on two different days. The
      volunteers were randomized to receive either 2 litres of Ringer acetate or no
      fluid during the following 3 hours. The sugar concentrations were measured in 5
      hour urine samples period. RESULTS: Fluid loading increased urine production and
      urinary recovery of xylose. Fluid loading did not influence the urinary recovery
      of 3-OMG, L-rhamnose, or lactulose. Neither the lactulose/rhamnose ratio nor the
      3-OMG/rhamnose ratio changed. CONCLUSION: Fluid loading increases mediated
      carbohydrate transport but not the lactulose/rhamnose ratio, after oral sugar
      administration in healthy volunteers. It remains to be determined whether sugar
      probes are handled differently in response to fluids in patients with organ
      dysfunctions.

PMID- 15987396
TI  - Effect of ventilator-associated tracheobronchitis on outcome in patients without
      chronic respiratory failure: a case-control study.
AB  - INTRODUCTION: Our objective was to determine the effect of ventilator-associated
      tracheobronchitis (VAT) on outcome in patients without chronic respiratory
      failure. METHODS: This was a retrospective observational matched study, conducted
      in a 30-bed intensive care unit (ICU). All immunocompetent, nontrauma, ventilated
      patients without chronic respiratory failure admitted over a 6.5-year period were
      included. Data were collected prospectively. Patients with nosocomial pneumonia,
      either before or after VAT, were excluded. Only first episodes of VAT occurring
      more than 48 hours after initiation of mechanical ventilation were studied. Six
      criteria were used to match cases with controls, including duration of mechanical
      ventilation before VAT. Cases were compared with controls using McNemar's test
      and Wilcoxon signed-rank test for qualitative and quantitative variables,
      respectively. Variables associated with a duration of mechanical ventilation
      longer than median were identified using univariate and multivariate analyses.
      RESULTS: Using the six criteria, it was possible to match 55 (87%) of the VAT
      patients (cases) with non-VAT patients (controls). Pseudomonas aeruginosa was the
      most frequently isolated bacteria (34%). Although mortality rates were similar
      between cases and controls (29% versus 36%; P = 0.29), the median duration of
      mechanical ventilation (17 days [range 3-95 days] versus 8 [3-61 days]; P <
      0.001) and ICU stay (24 days [range 5-95 days] versus 12 [4-74] days; P < 0.001)
      were longer in cases than in controls. Renal failure (odds ratio [OR] = 4.9, 95%
      confidence interval [CI] = 1.6-14.6; P = 0.004), tracheostomy (OR = 4, 95% CI =
      1.1-14.5; P = 0.032), and VAT (OR = 3.5, 95% CI = 1.5-8.3; P = 0.004) were
      independently associated with duration of mechanical ventilation longer than
      median. CONCLUSION: VAT is associated with longer durations of mechanical
      ventilation and ICU stay in patients not suffering from chronic respiratory
      failure.

PMID- 15987397
TI  - Use of intranasal mupirocin to prevent methicillin-resistant Staphylococcus
      aureus infection in intensive care units.
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) causes severe
      morbidity and mortality in intensive care units (ICUs) worldwide. The purpose of
      this study was to determine whether intranasal mupirocin prophylaxis is useful to
      prevent ICU-acquired infections with MRSA. MATERIALS AND METHODS: We conducted a
      4-year observational retrospective study in a 15-bed adult medical ICU. During
      the first 2-year period mupirocin ointment was included in the MRSA control
      programme; during the second, mupirocin was not used. The main endpoint was the
      number of endogenous ICU-acquired infections with MRSA. RESULTS: The number of
      endogenous acquired infections was significantly higher during the second period
      than during the first (11 versus 1; P = 0.02), although there was no significant
      difference in the total number of patients infected with MRSA between the two
      periods. We also observed that nasal MRSA decolonisation was significantly higher
      in the mupirocin period than in mupirocin-free period (P = 0.002). CONCLUSION:
      Our findings suggest that intranasal mupirocin can prevent endogenous acquired
      MRSA infection in an ICU. Further double-blind, randomised, placebo-controlled
      studies are needed to demonstrate its cost-effectiveness and its impact on
      resistance.

PMID- 15987399
TI  - Worldwide research productivity in critical care medicine.
AB  - INTRODUCTION: The number of publications and the impact factor of journals are
      accepted estimates of the quantity and quality of research productivity. The
      objective of the present study was to assess the worldwide scientific
      contribution in the field of critical care medicine. METHOD: All research studies
      published between 1995 and 2003 in medical journals that were listed in the 2003
      Science Citation Index (SCI) of Journal Citation Reports under the subheading
      'critical care' and also indexed in the PubMed database were reviewed in order to
      identify their geographical origin. RESULTS: Of 22,976 critical care publications
      in 14 medical journals, 17,630 originated from Western Europe and the USA
      (76.7%). A significant increase in the number of publications originated from
      Western European countries during the last 5 years of the study period was
      noticed. Scientific publications in critical care medicine increased
      significantly (25%) from 1995 to 2003, which was accompanied by an increase in
      the impact factor of the corresponding journals (47.4%). Canada and Japan had the
      better performance, based on the impact factor of journals. CONCLUSION:
      Significant scientific progress in critical care research took place during the
      period of study (1995-2003). Leaders of research productivity (in terms of
      absolute numbers) were Western Europe and the USA. Publications originating from
      Western European countries increased significantly in quantity and quality over
      the study period. Articles originating from Canada, Japan, and the USA had the
      highest mean impact factor. Canada was the leader in productivity when
      adjustments for gross domestic product and population were made.

PMID- 15987398
TI  - Influence of support on intra-abdominal pressure, hepatic kinetics of indocyanine
      green and extravascular lung water during prone positioning in patients with
      ARDS: a randomized crossover study.
AB  - INTRODUCTION: Prone positioning (PP) on an air-cushioned mattress is associated
      with a limited increase in intra-abdominal pressure (IAP) and an absence of organ
      dysfunction. The respective influence of posture by itself and the type of
      mattress on these limited modifications during the PP procedure remains unclear.
      The aim of this study was to evaluate whether the type of support modifies IAP,
      extravascular lung water (EVLW) and the plasma disappearance rate of indocyanine
      green (PDRICG) during PP. METHODS: A prospective, randomized, crossover study of
      20 patients with acute respiratory distress syndrome (ARDS) was conducted in a
      medical intensive care unit in a teaching hospital. Measurements were made at
      baseline and repeated after 1 and 6 hours of two randomized periods of 6 hours of
      PP with one of two support types: conventional foam mattress or air-cushioned
      mattress. RESULTS: After logarithmic transformation of the data, an analysis of
      variance (ANOVA) showed that IAP and PDRICG were significantly influenced by the
      type of support during PP with an increase in IAP (P < 0.05 by ANOVA) and a
      decrease in PDRICG on the foam mattress (P < 0.05 by ANOVA). Conversely, the
      measurements of EVLW did not show significant modification between the two
      supports whatever the posture. The ratio of the arterial oxygen tension to the
      fraction of inspired oxygen significantly increased in PP (P < 0.0001 by ANOVA)
      without any influence of the support. CONCLUSION: In comparison with a
      conventional foam mattress, the use of an air-cushioned mattress limited the
      increase in IAP and prevented the decrease in PDRICG related to PP in patients
      with ARDS. Conversely, the type of support did not influence EVLW or oxygenation.

PMID- 15987400
TI  - In vivo validation of the adequacy calculator for continuous renal replacement
      therapies.
AB  - INTRODUCTION: The study was conducted to validate in vivo the Adequacy
      Calculator, a Microsoft Excel-based program, designed to assess the prescription
      and delivery of renal replacement therapy in the critical care setting. METHODS:
      The design was a prospective cohort study, set in two intensive care units of
      teaching hospitals. The participants were 30 consecutive critically ill patients
      with acute renal failure treated with 106 continuous renal replacement therapies
      (CRRT). Urea clearance computation was performed with the Adequacy Calculator
      (KCALC). Simultaneous blood and effluent urea samples were collected to measure
      the effectively delivered urea clearance (KDEL) at the beginning of each
      treatment and, during 73 treatments, between the 18th and 24th treatment hour.
      The correlation between 179 computed and 179 measured clearances was assessed.
      Fractional clearances for urea were calculated as spKt/V (where sp represents
      single pool, K is clearance, t is time, and V is urea volume of distribution)
      obtained from software prescription and compared with the delivered spKt/V
      obtained from empirical data. RESULTS: We found that the value of clearance
      predicted by the calculator was strongly correlated with the value obtained from
      computation on blood and dialysate determination (r = 0.97) during the first 24
      treatment hours, regardless of the renal replacement modality used. The delivered
      spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by
      10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple
      tool for prescribing CRRT and for predicting the delivered dose. The calculator
      might be a helpful tool for standardizing therapy and for comparing disparate
      treatments, making it possible to perform large multi-centre studies on CRRT.

PMID- 15987401
TI  - High-frequency oscillatory ventilation in children: a single-center experience of
      53 cases.
AB  - INTRODUCTION: The present article reports our experience with high-frequency
      oscillatory ventilation (HFOV) in pediatric patients who deteriorated on
      conventional mechanical ventilation. METHODS: The chart records of 53
      consecutively HFOV-treated patients from 1 January 1998 to 1 April 2004 were
      retrospectively analyzed. The parameters of demographic data, cause of
      respiratory insufficiency, Pediatric Index of Mortality score, oxygenation index
      and PaCO2 were recorded and calculated at various time points before and after
      the start of HFOV, along with patient outcome and cause of death. RESULTS: The
      overall survival rate was 64%. We observed remarkable differences in outcome
      depending on the cause of respiratory insufficiency; survival was 56% in patients
      with diffuse alveolar disease (DAD) and was 88% in patients with small airway
      disease (SAD). The oxygenation index was significantly higher before and during
      HFOV in DAD patients than in SAD patients. The PaCO2 prior to HFOV was higher in
      SAD patients compared with DAD patients and returned to normal values after the
      initiation of HFOV. CONCLUSION: HFOV rescue therapy was associated with a high
      survival percentage in a selected group of children. Patients with DAD primarily
      had oxygenation failure. Future studies are necessary to evaluate whether the
      outcome in this group of patients may be improved if HFOV is applied earlier in
      the course of disease. Patients with SAD primarily had severe hypercapnia and
      HFOV therapy was very effective in achieving adequate ventilation.

PMID- 15987402
TI  - Fatality after deliberate ingestion of the pesticide rotenone: a case report.
AB  - Rotenone is a pesticide derived from the roots of plants from the Leguminosae
      family. Poisoning following deliberate ingestion of these plant roots has
      commonly been reported in Papua New Guinea. However, poisoning with commercially
      available rotenone in humans has been reported only once previously following
      accidental ingestion in a 3.5-year-old child. Therefore, the optimal management
      of rotenone poisoning is not known. After deliberate ingestion of up to 200 ml of
      a commercially available 0.8% rotenone solution, a 47-year-old female on regular
      metformin presented with a reduced level of consciousness, metabolic acidosis and
      respiratory compromise. Metformin was not detected in premortem blood samples
      obtained. Despite intensive supportive management, admission to an intensive care
      unit, and empirical use of N-acetylcysteine and antioxidant therapy, she did not
      survive. Poisoning with rotenone is uncommon but is potentially fatal because
      this agent inhibits the mitochondrial respiratory chain. In vitro cell studies
      have shown that rotenone-induced toxicity is reduced by the use of N
      acetylcysteine, antioxidants and potassium channel openers. However, no animal
      studies have been reported that confirm these findings, and there are no previous
      reports of attempted use of these agents in patients with acute rotenone-induced
      toxicity.

PMID- 15987403
TI  - Adhesion of the probiotic bacterium Lactobacillus plantarum 299v onto the gut
      mucosa in critically ill patients: a randomised open trial.
AB  - INTRODUCTION: To achieve any possible positive effect on the intestinal mucosa
      cells it is important that probiotics adhere tightly onto the intestinal mucosa.
      It has been shown in healthy volunteers that Lactobacillus plantarum 299v (Lp
      299v) (DSM 9843), a probiotic bacterium, given orally in a fermented oatmeal
      formula adheres onto the intestinal mucosa, but whether this also occurs in
      critically ill patients is unknown. METHODS: After randomisation, nine enterally
      fed, critically ill patients treated with broad-spectrum antibiotics received an
      oatmeal formula fermented with Lp 299v throughout their stay in the intensive
      care unit; eight patients served as controls. Biopsies of the rectal mucosa were
      made at admission and then twice a week, and the biopsies were analysed blindly.
      RESULTS: Four patients in the control group were colonised with Lp 299v at
      admission but thereafter all their biopsies were negative (Lp 299v is an
      ingredient in a common functional food, ProViva, in Sweden). Of the treated
      patients none was colonised at admission but three patients had Lp 299v adhered
      on the mucosa from the second or third biopsy and in the following samples.
      CONCLUSION: This study shows that Lp 299v could survive the passage from the
      stomach to the rectum and was able adhere onto the rectal mucosa also in
      critically ill, antibiotic-treated patients.

PMID- 15987404
TI  - Radiological weapons: what type of threat?

PMID- 15987405
TI  - Withdrawing may be preferable to withholding.
AB  - The majority of deaths on the intensive care unit now occur following a decision
      to limit life-sustaining therapy, and end-of-life decision making is an accepted
      and important part of modern intensive care medical practice. Such decisions can
      essentially take one of two forms: withdrawing -- the removal of a therapy that
      has been started in an attempt to sustain life but is not, or is no longer,
      effective -- and withholding -- the decision not to make further therapeutic
      interventions. Despite wide agreement by Western ethicists that there is no
      ethical difference between these two approaches, these issues continue to
      generate considerable debate. In this article, I will provide arguments why,
      although the two actions are indeed ethically equivalent, withdrawing life
      sustaining therapy may in fact be preferable to withholding.

PMID- 15987406
TI  - Withdrawing and withholding life-sustaining therapies are not the same.
AB  - Numerous lines of evidence support the premise that withholding and withdrawing
      life support measures in the intensive care unit are not the same. These include
      questionnaires, practical observations and an examination of national medical
      guidelines. It is important to distinguish between the two end of life options as
      their outcomes and management are significantly different. Appreciation of these
      differences allows the provision of accurate information, and facilitates
      decision making that is compassionate, caring and adherent to the needs of the
      patient and their family.

PMID- 15987407
TI  - Ethics roundtable debate: is a physician-patient confidentiality relationship
      subservient to a greater good?
AB  - Is a health care provider's most proximal obligation to individuals or society as
      a whole? Our International panel of critical care providers grapple over the
      issue of whether patient-physician confidentiality exists as an open ended ideal
      it should be subservient to a greater good.

PMID- 15987408
TI  - Recently published papers: out with the old and in with the new ... then
      something new for the old!
AB  - New therapies are challenging older, established practices. One recently
      published report shows us that we may be able to avoid endotracheal intubation in
      patients with a reduced level of consciousness. Recombinant activated factor VII
      is proving to be useful in many coagulation disorders, and intracerebral
      haemorrhage can be added to this list. Homeopathy, in the form of potassium
      dichromate, shows promise as a new treatment for excessive tracheal secretions.
      Rotation protocols for antibiotics have been evaluated with respect to their
      ability to prevent the development of new resistant micro-organisms in our
      hospitals and units. Finally, glucocorticoids may be of benefit to septic
      patients outside the intensive care unit (ICU) and may prevent their
      deterioration and admission to the ICU.

PMID- 15987409
TI  - French multicentre survey on the use of inotropes after cardiac surgery.
AB  - Results from a French multicentre survey on the use of inotropes after cardiac
      surgery are presented. Consideration of these findings, which strictly apply only
      to France, highlights the importance of developing monitoring strategies to help
      in decision making regarding therapy with inotropes in this context.

PMID- 15987410
TI  - Acute pancreatitis: a possible role for activated protein C?
AB  - Acute pancreatitis results from a sequence of events that involve the systemic
      inflammatory response. Activated C has multiple anti-inflammatory activities and
      may attenuate the degree of pancreatic injury and systemic organ dysfunction when
      infused early in pancreatitis.

PMID- 15987411
TI  - Endothelin antagonists: new bullets against lung injury?
AB  - Acute lung injury is a syndrome of inflammation and of increased permeability of
      the blood-gas barrier. Endothelins are thought to exert proinflammatory effects.
      Kuklin and colleagues show that the endothelin receptor antagonist tezosentan
      reduces pulmonary edema in endotoxemic sheep, in parallel with a prevention of
      protein kinase C-alpha activation. In turn, the level of some cytokines increased
      after tezosentan treatment. Whether these contrasting effects of endothelin
      blockade on inflammatory mechanisms have clinical relevance and whether these
      agents might benefit patients with acute lung injury is unknown.

PMID- 15987412
TI  - Narcotic-based sedation regimens for critically ill mechanically ventilated
      patients.
AB  - Sedatives and analgesics are routinely used in the intensive care unit to relieve
      pain and anxiety. These agents have numerous side effects and may contribute to
      poor outcomes such as increased length of mechanical ventilation, longer ICU
      stays and acute and long-term cognitive dysfunction. Modifying sedation paradigms
      utilizing either narcotic-based regimens with remifentanil or fentanyl, or by
      using alpha2 agonists such as dexmedetomidine may help in improving these
      outcomes in critically ill patients.

PMID- 15987413
TI  - The role of high-frequency oscillatory ventilation in paediatric intensive care.
AB  - Mechanical ventilation during acute respiratory failure in children is associated
      with development of ventilator-induced lung injury. Experimental models of
      mechanical ventilation that limit phasic changes in lung volumes and prevent
      alveolar overdistension appear to be less damaging to the lung. High-frequency
      oscillatory ventilation, using very small tidal volumes and relatively high end
      expiratory lung volumes, provides a safe and effective means of delivering
      mechanical ventilatory support with the prospect of reducing the development of
      ventilator-induced lung injury. Despite theoretical advantages and convincing
      laboratory data, however, the use of high-frequency oscillatory ventilation in
      the paediatric population has not yet been associated with significant
      improvements in clinically significant outcome measures.

PMID- 15987414
TI  - Intensive care unit nutrition -- nonsense or neglect?
AB  - Systematic undernutrition of intensive care unit patients is common and
      neglected. Is this inevitable or can better routines and protocols make a
      difference? The necessity of feeding may be regarded as self-evident, but more
      evidence is obviously needed to strengthen this issue. In rich countries it
      should be a human right not to be hungry.

PMID- 15987415
TI  - Prone position in mechanically ventilated patients -- the hard or the soft way?
AB  - Prone positioning may even in patients without abdominal hypertension result in
      an increased intra-abdominal pressure (IAP). Previous research could not
      demonstrate a marked increase in IAP associated with cardiovascular, renal, or
      hepato-splanchnic dysfunction when patients were proned in air-cushioned beds.
      Michelet and colleagues in this issue of Critical Care report that the increase
      in IAP in the prone position depends on the used mattress type. Compared with air
      cushion beds, conventional foam mattresses resulted in a greater increase in IAP
      which was associated with a decrease in the plasma disappearance rate of
      indocyanin green (PDRICG) indicating inadequate heptosplanchnic function.

PMID- 15987416
TI  - Does ventilator-associated tracheobronchitis need antibiotic treatment?
AB  - It is difficult to define ventilator-associated tracheobronchitis (VAT). The most
      accepted definition includes fever (temperature > 38 degrees C), new or increased
      sputum production, a microbiologically positive respiratory sample with counts
      above the accepted thresholds and absence of pulmonary infiltrates on chest X
      ray. Although we have no doubt that this pathologic process exists, the main
      controversy lies on whether this entity has any impact on the outcome and, thus,
      a specific therapeutic approach is suitable. We will discuss the strengths and
      drawbacks of the article on this topic published in this issue by Nseir et al.

PMID- 15987417
TI  - Can mupirocin prevent methicillin-resistant Staphylococcus aureus infections?
AB  - In a retrospective study, Dr Muller and colleagues have assessed the efficacy of
      mupirocin nasal ointment alongside hygienic measures in methicillin-resistant
      Staphylococcus aureus (MRSA)-positive patients admitted to the intensive care
      unit (ICU). Their findings, which suggest that intranasal mupirocin can prevent
      ICU-related MRSA infections, need confirmation in a well-designed clinical trial.
      In general: early identification, isolation and treatment of all MRSA carriers,
      including health care workers, and disinfection of contaminated environments, are
      the main 'ingredients' of an effective MRSA 'search and destroy' program.

PMID- 15987418
TI  - Bench-to-bedside review: Biotrauma and modulation of the innate immune response.
AB  - The innate immune network is responsible for coordinating the initial defense
      against potentially noxious stimuli. This complex system includes anatomical,
      physical and chemical barriers, effector cells and circulating molecules that
      direct component and system interactions. Besides the direct effects of breaching
      pulmonary protective barriers, cyclic stretch generated during mechanical
      ventilation (MV) has been implicated in the modulation of the innate immunity.
      Evidence from recent human trials suggests that controlling MV-forces may
      significantly impact outcome in acute respiratory distress syndrome. In this
      paper, we explore the pertinent evidence implicating biotrauma caused by cyclic
      MV and its effect on innate immune responses.

PMID- 15987420
TI  - Between benzodiazepine over-sedation and neurological damage.

PMID- 15987421
TI  - Hemorrhagic shock, drag-reducing polymers and 'spherical cows'.

PMID- 15987422
TI  - Clonogenic growth of human breast cancer cells co-cultured in direct contact with
      serum-activated fibroblasts.
AB  - INTRODUCTION: Accumulating evidence suggests that fibroblasts play a pivotal role
      in promoting the growth of breast cancer cells. The objective of the present
      study was to characterize and validate an in vitro model of the interaction
      between small numbers of human breast cancer cells and human fibroblasts.
      METHODS: We measured the clonogenic growth of small numbers of human breast
      cancer cells co-cultured in direct contact with serum-activated, normal human
      fibroblasts. Using DNA microarrays, we also characterized the gene expression
      profile of the serum-activated fibroblasts. In order to validate the in vivo
      relevance of our experiments, we then analyzed clinical samples of metastatic
      breast cancer for the presence of myofibroblasts expressing alpha-smooth muscle
      actin. RESULTS: Clonogenic growth of human breast cancer cells obtained directly
      from in situ and invasive tumors was dramatically and consistently enhanced when
      the tumor cells were co-cultured in direct contact with serum-activated
      fibroblasts. This effect was abolished when the cells were co-cultured in
      transwells separated by permeable inserts. The fibroblasts in our experimental
      model exhibited a gene expression signature characteristic of 'serum response'
      (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast
      cancer tissue confirmed that myofibroblasts are in direct contact with breast
      cancer cells. CONCLUSION: Serum-activated fibroblasts promote the clonogenic
      growth of human breast cancer cells in vitro through a mechanism that involves
      direct physical contact between the cells. This model shares many important
      molecular and phenotypic similarities with the fibroblasts that are naturally
      found in breast cancers.

PMID- 15987423
TI  - Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal
      breast cancer patients.
AB  - BACKGROUND: Tamoxifen is widely used as endocrine therapy for oestrogen-receptor
      positive breast cancer. However, many of these patients experience recurrence
      despite tamoxifen therapy by incompletely understood mechanisms. In the present
      report we propose that tamoxifen resistance may be due to differences in activity
      of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6
      (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in
      the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in
      decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and
      SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant
      tamoxifen treatment in order to validate the benefit from the therapy. METHODS:
      The patients were genotyped using PCR followed by cleavage with restriction
      enzymes. RESULTS: Carriers of the CYP2D6*4 allele demonstrated a decreased risk
      of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence
      interval = 0.11-0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1
      homozygotes (relative risk = 0.48, 95% confidence interval = 0.21-1.12, P =
      0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60%
      of the patients and showed a 62% decreased risk of distant recurrence with
      tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19-0.74, P =
      0.0041). CONCLUSION: The present study suggests that genotype of metabolic
      enzymes might be useful as a guide for adjuvant endocrine treatment of
      postmenopausal breast cancer patients. However, results are in contradiction to
      prior hypotheses and the present sample size is relatively small. Findings
      therefore need to be confirmed in a larger cohort.

PMID- 15987424
TI  - Modulation of N-methyl-N-nitrosourea induced mammary tumors in Sprague-Dawley
      rats by combination of lysine, proline, arginine, ascorbic acid and green tea
      extract.
AB  - INTRODUCTION: The limited ability of current treatments to control metastasis and
      the proposed antitumor properties of specific nutrients prompted us to examine
      the effect of a specific formulation (nutrient supplement [NS]) of lysine,
      proline, arginine, ascorbic acid, and green tea extract in vivo on the
      development of N-methyl-N-nitrosourea (MNU)-induced mammary tumors in rats.
      METHODS: A single intraperitoneal dose of MNU was injected into each of 20 female
      Sprague-Dawley rats (aged 50 days) to induce tumors. Two weeks after MNU
      treatment, a time by which the animals had recovered from MNU-induced toxicity,
      the rats were divided into two groups. Rats in group 1 (n = 10) were fed Purina
      chow diet, whereas those in group 2 (n = 10) were fed the same diet supplemented
      with 0.5% NS. After a further 24 weeks, the rats were killed and tumors were
      excised and processed. RESULTS: NS reduced the incidence of MNU-induced mammary
      tumors and the number of tumors by 68.4%, and the tumor burden by 60.5%. The
      inhibitory effect of NS was also reflected by decreased tumor weight; the tumor
      weights per rat and per group were decreased by 41% and 78%, respectively. In
      addition, 30% of the control rats developed ulcerated tumors, in contrast to 10%
      in the nutrient supplemented rats. CONCLUSION: These findings suggest that the
      specific formulation of lysine, proline, arginine, ascorbic acid, and green tea
      extract tested significantly reduces the incidence and growth of MNU-induced
      mammary tumors, and therefore has strong potential as a useful therapeutic
      regimen for inhibiting breast cancer development.

PMID- 15987425
TI  - Assessment of the proliferative, apoptotic and cellular renovation indices of the
      human mammary epithelium during the follicular and luteal phases of the menstrual
      cycle.
AB  - INTRODUCTION: During the menstrual cycle, the mammary gland goes through
      sequential waves of proliferation and apoptosis. In mammary epithelial cells,
      hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical
      effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic
      index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) staining in human mammary epithelial cells during the
      spontaneous menstrual cycle and correlated it with cellular proliferation as
      determined by the expression of Ki-67 during the same period. METHODS: Normal
      breast tissue samples were obtained from 42 randomly selected patients in the
      proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase
      characterization was based on the date of the last and subsequent menses, and on
      progesterone serum levels obtained at the time of biopsy. RESULTS: The
      proliferation index (PI), defined as the number of Ki-67-positive nuclei per
      1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than
      in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of
      TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both
      phases of the menstrual cycle were not statistically significant (P = 0.21).
      However, the cell renewal index (CRI = PI/AI) was significantly higher in the
      luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was
      observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle,
      whereas the CRI reached higher values on the 28th day. CONCLUSIONS: We conclude
      that proliferative activity is dependent mainly on hormonal fluctuations, whereas
      apoptotic activity is probably regulated by hormonal and non-hormonal factors.

PMID- 15987426
TI  - Body fatness during childhood and adolescence and incidence of breast cancer in
      premenopausal women: a prospective cohort study.
AB  - INTRODUCTION: Body mass index (BMI) during adulthood is inversely related to the
      incidence of premenopausal breast cancer, but the role of body fatness earlier in
      life is less clear. We examined prospectively the relation between body fatness
      during childhood and adolescence and the incidence of breast cancer in
      premenopausal women. METHODS: Participants were 109,267 premenopausal women in
      the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20
      years using a validated 9-level figure drawing. Over 12 years of follow up, 1318
      incident cases of breast cancer were identified. Cox proportional hazards
      regression was used to compute relative risks (RRs) and 95% confidence intervals
      (CIs) for body fatness at each age and for average childhood (ages 5-10 years)
      and adolescent (ages 10-20 years) fatness. RESULTS: Body fatness at each age was
      inversely associated with premenopausal breast cancer incidence; the multivariate
      RRs were 0.48 (95% CI 0.35-0.55) and 0.57 (95% CI 0.39-0.83) for the most
      overweight compared with the most lean in childhood and adolescence, respectively
      (P for trend < 0.0001). The association for childhood body fatness was only
      slightly attenuated after adjustment for later BMI, with a multivariate RR of
      0.52 (95% CI 0.38-0.71) for the most overweight compared with the most lean (P
      for trend = 0.001). Adjustment for menstrual cycle characteristics had little
      impact on the association. CONCLUSION: Greater body fatness during childhood and
      adolescence is associated with reduced incidence of premenopausal breast cancer,
      independent of adult BMI and menstrual cycle characteristics.

PMID- 15987427
TI  - Dendritic cells are defective in breast cancer patients: a potential role for
      polyamine in this immunodeficiency.
AB  - INTRODUCTION: Dendritic cells (DCs) are antigen-presenting cells that are
      currently employed in cancer clinical trials. However, it is not clear whether
      their ability to induce tumour-specific immune responses when they are isolated
      from cancer patients is reduced relative to their ability in vivo. We determined
      the phenotype and functional activity of DCs from cancer patients and
      investigated the effect of putrescine, a polyamine molecule that is released in
      large amounts by cancer cells and has been implicated in metastatic invasion, on
      DCs. METHODS: The IL-4/GM-CSF (granulocyte-macrophage colony-stimulating factor)
      procedure for culturing blood monocyte-derived DCs was applied to cells from
      healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal
      cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used
      for DC pulsing. We investigated the effects of stimulation of autologous
      lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic
      activity of T cells was determined in the same target cells. RESULTS: Certain
      differences were observed between donors and breast cancer patients. The yield of
      DCs was dramatically weaker, and expression of MHC class II was lower and the
      percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of
      maturating agents was used, expression of markers of mature DCs was significantly
      lower in patients. Also, DCs from patients exhibited reduced ability to stimulate
      cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was
      enhanced by up to 40% when DCs were from donors but only up to 10% when they were
      from patients. IFN-gamma production was repeatedly found to be enhanced in donors
      but not in patients. By adding putrescine to DCs from donors, it was possible to
      enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic
      activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function.
      These putrescine-induced deficiencies were reversed by treating DCs with all
      trans retinoic acid. CONCLUSION: These data are consistent with blockade of
      antigen-presenting cells at an early stage of differentiation in patients with
      breast cancer. Putrescine released in the microenvironmement of DCs could be
      involved in this blockade. Use of all-trans retinoic acid treatment to reverse
      this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is
      of real interest.

PMID- 15987428
TI  - Polymorphisms in genes involved in estrogen and progesterone metabolism and
      mammographic density changes in women randomized to postmenopausal hormone
      therapy: results from a pilot study.
AB  - INTRODUCTION: Mammographic density is a strong independent risk factor for breast
      cancer, and can be modified by hormonal exposures. Identifying genetic variants
      that determine increases in mammographic density in hormone users may be
      important in understanding hormonal carcinogenesis of the breast. METHODS: We
      obtained mammograms and DNA from 232 postmenopausal women aged 45 to 75 years who
      had participated in one of two randomized, double-blind clinical trials with
      estrogen therapy (104 women, taking 1 mg/day of micronized 17beta-estradiol, E2),
      combined estrogen and progestin therapy (34 women, taking 17beta-estradiol and 5
      mg/day of medroxyprogesterone acetate for 12 days/month) or matching placebos (94
      women). Mammographic percentage density (MPD) was measured on baseline and 12
      month mammograms with a validated computer-assisted method. We evaluated
      polymorphisms in genes involved in estrogen metabolism (catechol-O
      methyltransferase (COMT (Val158Met)), cytochrome P450 1B1 (CYP1B1 (Val432Leu)),
      UDP-glucuronosyltransferase 1A1 (UGT1A1 (<7/>or= 7 TA repeats))) and progesterone
      metabolism (aldo-keto reductase 1C4 (AKR1C4 (Leu311Val))) with changes in MPD.
      RESULTS: The adjusted mean change in MPD was +4.6% in the estrogen therapy arm
      and +7.2% in the combined estrogen and progestin therapy arm, compared with
      +0.02% in the placebo arm (P = 0.0001). None of the genetic variants predicted
      mammographic density changes in women using estrogen therapy. Both the AKR1C4 and
      the CYP1B1 polymorphisms predicted mammographic density change in the combined
      estrogen and progestin therapy group (P < 0.05). In particular, the eight women
      carrying one or two low-activity AKR1C4 Val alleles showed a significantly
      greater increase in MPD (16.7% and 29.3%) than women homozygous for the Leu
      allele (4.0%). CONCLUSION: Although based on small numbers, these findings
      suggest that the magnitude of the increase in mammographic density in women using
      combined estrogen and progestin therapy may be greater in those with genetically
      determined lower activity of enzymes that metabolize estrogen and progesterone.

PMID- 15987429
TI  - Muscarinic receptors participation in angiogenic response induced by macrophages
      from mammary adenocarcinoma-bearing mice.
AB  - INTRODUCTION: The role of macrophages in tumor progression has generated
      contradictory evidence. We had previously demonstrated the ability of peritoneal
      macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to
      increase the angiogenicity of LMM3 tumor cells, mainly through polyamine
      synthesis. Here we investigate the ability of the parasympathetic nervous system
      to modulate angiogenesis induced by TMps through the activation of the muscarinic
      acetylcholine receptor (mAchR). METHODS: Peritoneal macrophages from female
      BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 x 10(5)
      cells per site) into syngeneic mice. Before inoculation, TMps were stimulated
      with the muscarinic agonist carbachol in the absence or presence of different
      muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by
      counting vessels per square millimeter of skin. The expression of mAchR, arginase
      and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and
      COX activities were evaluated by urea and prostaglandin E2 (PGE2) production,
      respectively. RESULTS: TMps, which stimulate neovascularization, express
      functional mAchR, because carbachol-treated TMps potently increased new blood
      vessels formation. This response was completely blocked by preincubating TMps
      with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3
      receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1
      receptor activation by carbachol in TMps triggers neovascularization through
      arginase products because Nomega-hydroxy-L-arginine reversed the agonist action.
      Preincubation of TMps with methoctramine partly prevented carbachol-stimulated
      urea formation. In addition, COX-derived liberation of PGE2 is responsible for
      the promotion of TMps angiogenic activity by M3 receptor. We also detected a
      higher expression of vascular endothelial growth factor (VEGF) in TMps than in
      macrophages from normal mice. Carbachol significantly increased VEGF expression
      in TMps, and this effect was totally reversed by methoctramine and pirenzepine.
      Arginase and COX inhibitors partly decreased VEGF derived from TMps. CONCLUSION:
      TMps themselves induce a potent angiogenic response that is augmented by
      carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis
      and VEGF production, promoting neovascularization.

PMID- 15987430
TI  - The AIB1 glutamine repeat polymorphism is not associated with risk of breast
      cancer before age 40 years in Australian women.
AB  - INTRODUCTION: AIB1, located at 20q12, is a member of the steroid hormone
      coactivator family. It contains a glutamine repeat (CAG/CAA) polymorphism at its
      carboxyl-terminal region that may alter the transcriptional activation of the
      receptor and affect susceptibility to breast cancer through altered sensitivity
      to hormones. METHODS: We evaluated this repeat polymorphism in the context of
      early-onset disease by conducting a case-control study of 432 Australian women
      diagnosed with breast cancer before the age of 40 years and 393 population-based
      control individuals who were frequency matched for age. Genotyping was performed
      using a scanning laser fluorescence imager. RESULTS: There were no differences in
      genotype frequencies between cases and control individuals, or between cases
      categorized by family history or by BRCA1 and BRCA2 germline mutation status.
      There was no evidence that the presence of one or two alleles of 26 glutamine
      repeats or fewer was associated with breast cancer (odds ratio = 1.03, 95%
      confidence interval = 0.73-1.44), or that women with alleles greater than 29
      repeats were at increased risk of breast cancer. Exclusion of women who carried a
      BRCA1 or BRCA2 mutation (24 cases) and non-Caucasian women (44 cases) did not
      alter the risk estimates or inferences. We present raw data, including that on
      mutation carriers, to allow pooling with other studies. CONCLUSION: There was no
      evidence that risk of breast cancer depends on AIB1 CAG/CAA polymorphism status,
      even if affected women carry a mutation in BRCA1 or BRCA2.

PMID- 15987431
TI  - A case-control study of the HER2 Ile655Val polymorphism in relation to risk of
      invasive breast cancer.
AB  - BACKGROUND: Overexpression of the HER2 proto-oncogene in human cancer cells has
      been associated with a poor prognosis, and survival improves with therapy
      targeting the HER2 gene. Animal studies and protein modeling suggest that the
      Ile655Val polymorphism located in the transmembrane domain of the HER2 protein
      might influence breast cancer development by altering the efficiency of
      homodimerization. METHODS: To investigate this genetic polymorphism, incident
      cases of invasive breast cancer (N = 1,094) and population controls of a similar
      age (N = 976) were interviewed during 2001 to 2003 regarding their risk factors
      for breast cancer. By using DNA collected from buccal samples mailed by the
      participants, the HER2 Ile655Val polymorphism was evaluated with the Applied
      Biosystems allelic discrimination assay. Odds ratios (ORs) and 95% confidence
      intervals (95% CIs) were estimated by logistic regression adjusted for numerous
      breast cancer risk factors. Analysis was restricted to women with self-reported
      European descent. RESULTS: Prevalence of the Val/Val genotype was 5.6% in cases
      and 7.1% in controls. In comparison with the Ile/Ile genotype, the Ile/Val
      genotype was not significantly associated with breast cancer risk (OR 0.97, 95%
      CI 0.79 to 1.18), whereas the Val/Val genotype was associated with a reduced risk
      (OR 0.63, 95% CI 0.42 to 0.92). This inverse association seemed strongest in
      older women (OR 0.51, 95% CI 0.29 to 0.89 for women aged more than 55 years),
      women without a family history of breast cancer (OR 0.54, 95% CI 0.35 to 0.84),
      postmenopausal women with greater body mass index (OR 0.43, 95% CI 0.20 to 0.91
      for a body mass index of 25.3 kg/m2 or more), and cases diagnosed with non
      localized breast cancer (OR 0.49, 95% CI 0.26 to 0.90). CONCLUSION: Although
      results from our population-based case-control study show an inverse association
      between the HER2 Ile655Val polymorphism and risk of invasive breast cancer, most
      other studies of this single-nucleotide polymorphism suggest an overall null
      association. Any further study of this polymorphism should involve sample
      populations with complete risk factor information and sufficient power to
      evaluate gene-environment interactions between the HER2 polymorphism and factors
      such as age and family history of breast cancer.

PMID- 15987432
TI  - The membrane cytoskeletal crosslinker ezrin is required for metastasis of breast
      carcinoma cells.
AB  - INTRODUCTION: The membrane cytoskeletal crosslinker ezrin participates in several
      functions including cell adhesion, motility and cell survival, and there is
      increasing evidence that it regulates tumour progression. However, the role
      played by ezrin in breast cancer metastasis has not been clearly delineated.
      METHODS: We examined the role of ezrin in metastasis using a highly metastatic
      murine mammary carcinoma cell line, namely AC2M2. Stable cell clones that
      overexpress wild-type ezrin or a dominant-negative amino-terminal domain of ezrin
      were selected. They were then tested for cell motility and invasion in vitro, and
      metastasis in a mouse in vivo tumour transplantation model. RESULTS: Parental
      AC2M2 cells and cells overexpressing wild-type ezrin were transplanted into the
      mammary fat pad of syngeneic recipient mice; these animals subsequently developed
      lung metastases. In contrast, expression of the dominant-negative amino-terminal
      ezrin domain markedly inhibited lung metastasis. Consistent with this effect, we
      observed that the expression of amino-terminal ezrin caused strong membrane
      localization of cadherin, with increased cell-cell contact and a decrease in cell
      motility and invasion, whereas cells expressing wild-type ezrin exhibited strong
      cytoplasmic expression of cadherins and pseudopodia extensions. In addition,
      inhibitors of phosphatidylinositol 3-kinase and c-Src significantly blocked cell
      motility and invasion of AC2M2 cells expressing wild-type ezrin. We further found
      that overexpression of amino-terminal ezrin reduced levels of Akt pS473 and
      cytoskeletal-associated c-Src pY418 in AC2M2 cells, which contrasts with the high
      levels of phosphorylation of these proteins in cells expressing wild-type ezrin.
      Phosphorylated Erk1/2 was also reduced in amino-terminal ezrin expressing cells,
      although a mitogen-activated protein kinase kinase (MEK) inhibitor had no
      detectable effect on cell motility or invasion in this system. CONCLUSION: Our
      findings indicate that ezrin is required for breast cancer metastasis, and that c
      Src and phosphatidylinositol 3-kinase/Akt are effectors of ezrin in the cell
      motility and invasion stages of the metastatic process. Together, these results
      suggest that blocking ezrin function may represent a novel and effective strategy
      for preventing breast cancer metastasis.

PMID- 15987433
TI  - c-erbB2 and topoisomerase IIalpha protein expression independently predict poor
      survival in primary human breast cancer: a retrospective study.
AB  - INTRODUCTION: c-erbB2 (also known as HER-2/neu) and topoisomerase IIalpha are
      frequently overexpressed in breast cancer. The aim of the study was to analyze
      retrospectively whether the expression of c-erbB2 and topoisomerase IIalpha
      protein influences the long-term outcome of patients with primary breast cancer.
      METHODS: In this study c-erbB2 and topoisomerase IIalpha protein were evaluated
      by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225
      samples of primary breast cancer, obtained between 1986 and 1998. The prognostic
      value of these markers was analyzed. RESULTS: Of 225 primary breast tumor
      samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or
      topoisomerase IIalpha protein (24.9%), whereas in 21 tumors (9.3%) both proteins
      were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase
      IIalpha overexpression had the best long-term survival. Overexpression of either
      c-erbB2 or topoisomerase IIalpha was associated with shortened survival, whereas
      patients overexpressing both c-erbB2 and topoisomerase IIalpha showed the worst
      disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of
      reversing the negative prognostic impact of topoisomerase IIalpha or c-erbB2
      overexpression. CONCLUSION: The results of this exploratory study suggest that
      protein expression of c-erbB2 and topoisomerase IIalpha in primary breast cancer
      tissues are independent prognostic factors and are not exclusively predictive
      factors for anthracycline response in patients with primary breast cancer.

PMID- 15987434
TI  - A case-only analysis of the interaction between N-acetyltransferase 2 haplotypes
      and tobacco smoke in breast cancer etiology.
AB  - INTRODUCTION: N-acetyltransferase 2 is a polymorphic enzyme in humans. Women who
      possess homozygous polymorphic alleles have a slower rate of metabolic activation
      of aryl aromatic amines, one of the constituents of tobacco smoke that has been
      identified as carcinogenic. We hypothesized that women with breast cancer who
      were slow acetylators would be at increased risk of breast cancer associated with
      active and passive exposure to tobacco smoke. METHODS: We used a case-only study
      design to evaluate departure from multiplicativity between acetylation status and
      smoking status. We extracted DNA from buccal cell samples collected from 502
      women with incident primary breast cancer and assigned acetylation status by
      genotyping ten single-nucleotide polymorphisms. Information on tobacco use and
      breast cancer risk factors was obtained by structured interviews. RESULTS: We
      observed no substantial departure from multiplicativity between acetylation
      status and history of ever having been an active smoking (adjusted odds ratio
      estimate of departure from multiplicativity = 0.9, 95% confidence interval 0.5 to
      1.7) or ever having had passive residential exposure to tobacco smoke (adjusted
      odds ratio = 0.7, 95% confidence interval 0.4 to 1.5). The estimates for
      departure from multiplicativity between acetylation status and various measures
      of intensity, duration, and timing of active and passive tobacco exposure lacked
      consistency and were generally not supportive of the idea of a gene-environment
      interaction. CONCLUSION: In this, the largest case-only study to evaluate the
      interaction between acetylation status and active or passive exposure to tobacco
      smoke, we found little evidence to support the idea of a departure from
      multiplicativity.

PMID- 15987435
TI  - Breast cancer and childhood anthropometry: emerging hypotheses?
AB  - In this issue of Breast Cancer Research, Baer and colleagues report a strong
      protective effect of childhood and adolescent body fatness on premenopausal
      breast cancer risk based on a large prospective study. Methodological issues are
      discussed, as are tentative biological interpretations regarding the findings.

PMID- 15987436
TI  - Mammary stem cells, self-renewal pathways, and carcinogenesis.
AB  - The mammary gland epithelial components are thought to arise from stem cells that
      undergo both self-renewal and differentiation. Self-renewal has been shown to be
      regulated by the Hedgehog, Notch, and Wnt pathways and the transcription factor B
      lymphoma Mo-MLV insertion region 1 (Bmi-1). We review data about the existence of
      stem cells in the mammary gland and the pathways regulating the self-renewal of
      these cells. We present evidence that deregulation of the self-renewal in stem
      cells/progenitors might be a key event in mammary carcinogenesis. If 'tumor stem
      cells' are inherently resistant to current therapies, targeting stem cell self
      renewal pathways might provide a novel approach for breast cancer treatment.

PMID- 15987437
TI  - Microarrays and breast cancer clinical studies: forgetting what we have not yet
      learnt.
AB  - This review takes a sceptical view of the impact of breast cancer studies that
      have used microarrays to identify predictors of clinical outcome. In addition to
      discussing general pitfalls of microarray experiments, we also critically review
      the key breast cancer studies to highlight methodological problems in cohort
      selection, statistical analysis, validation of results and reporting of raw data.
      We conclude that the optimum use of microarrays in clinical studies requires
      further optimisation and standardisation of methodology and reporting, together
      with improvements in clinical study design.

PMID- 15987438
TI  - The promise of microarrays in the management and treatment of breast cancer.
AB  - Breast cancer is the most common malignancy afflicting women from Western
      cultures. Developments in breast cancer molecular and cellular biology research
      have brought us closer to understanding the genetic basis of this disease. Recent
      advances in microarray technology hold the promise of further increasing our
      understanding of the complexity and heterogeneity of this disease, and providing
      new avenues for the prognostication and prediction of breast cancer outcomes.
      These new technologies have some limitations and have yet to be incorporated into
      clinical use, for both the diagnosis and treatment of women with breast cancer.
      The most recent application of microarray genomic technologies to studying breast
      cancer is the focus of this review.

PMID- 15987439
TI  - Accelerated partial breast irradiation: the case for current use.
AB  - The treatment of early stage breast cancer is evolving from traditional breast
      conservation techniques, employing conventionally fractionated whole breast
      irradiation, to techniques in which partial breast irradiation is used in an
      accelerated fractionation scheme. A growing body of evidence exists, including
      favorable findings. Additional studies are under way that may ultimately prove
      equivalence. The logic behind this approach is reviewed, and the currently
      available data are presented to support the current use of carefully applied
      partial breast irradiation techniques in appropriately selected and informed
      patients.

PMID- 15987440
TI  - Accelerated partial breast irradiation: technically feasible but who will
      benefit?
AB  - Modern breast cancer radiotherapy aims to increase uncomplicated cure rates. A
      priority is reduction of late effects which include chronic chest wall or breast
      pain, poor cosmesis, and cardiac toxicity. As breast screening detects early
      cancers we may be able to safely restrict irradiation postlumpectomy to the
      tumour bed with a margin, defining a 'partial breast' target volume for
      treatment. Differing technical approaches to partial breast irradiation are being
      evaluated in phase III studies with standard whole breast irradiation. These
      include intra-operative single doses, hypo-fractionated accelerated
      brachytherapy, and LINAC (linear accelerator)-based three-dimensional external
      beam therapy.

PMID- 15987441
TI  - Keystone symposium: the role of microenvironment in tumor induction and
      progression, Banff, Canada, 5-10 February 2005.
AB  - The first Keystone symposium on the role of microenvironment in tumor induction
      and progression attracted 274 delegates from 13 countries to Banff in the heart
      of the Canadian Rockies. The meeting was organized by Mina Bissell, Ronald
      DePinho and Luis Parada, and was held concurrently with the Keystone symposium on
      cancer and development, chaired by Matthew Scott and Roeland Nusse. The 30 oral
      presentations and over 130 posters provided an excellent forum for discussing
      emerging data in this rapidly advancing field.

PMID- 15987442
TI  - Endocrinology and hormone therapy in breast cancer: selective oestrogen receptor
      modulators and downregulators for breast cancer - have they lost their way?
AB  - Although tamoxifen has been an effective treatment for breast cancer, several
      novel anti-oestrogen compounds have been developed with a reduced agonist profile
      on breast and gynaecological tissues. These include selective oestrogen receptor
      modulators (SERMs; both 'tamoxifen-like' and 'fixed-ring' SERMs) and selective
      oestrogen receptor downregulators (SERDs), although none has been proved superior
      in efficacy to tamoxifen in various advanced breast cancer trials. Thus, many
      have questioned whether a need for SERMs in breast cancer still exists, although
      chemoprevention remains a possible niche setting. In contrast, SERDs may have
      useful efficacy following aromatase inhibitors because of their unique mechanism
      of action, and clinical trials to determine their optimal use or sequence are
      ongoing.

PMID- 15987443
TI  - The protective role of pregnancy in breast cancer.
AB  - Epidemiological, clinical, and experimental data indicate that the risk of
      developing breast cancer is strongly dependent on the ovary and on endocrine
      conditions modulated by ovarian function, such as early menarche, late menopause,
      and parity. Women who gave birth to a child when they were younger than 24 years
      of age exhibit a decrease in their lifetime risk of developing breast cancer, and
      additional pregnancies increase the protection. The breast tissue of normally
      cycling women contains three identifiable types of lobules, the undifferentiated
      Lobules type 1 (Lob 1) and the more developed Lobules type 2 and Lobules type 3.
      The breast attains its maximum development during pregnancy and lactation
      (Lobules type 4). After menopause the breast regresses in both nulliparous and
      parous women containing only Lob 1. Despite the similarity in the lobular
      composition of the breast at menopause, the fact that nulliparous women are at
      higher risk of developing breast cancer than parous women indicates that Lob 1 in
      these two groups of women might be biologically different, or might exhibit
      different susceptibility to carcinogenesis. Based on these observations it was
      postulated that Lob 1 found in the breast of nulliparous women and of parous
      women with breast cancer never went through the process of differentiation,
      retaining a high concentration of epithelial cells that are targets for
      carcinogens and are therefore susceptible to undergo neoplastic transformation.
      These epithelial cells are called Stem cells 1, whereas Lob 1 structures found in
      the breast of early parous postmenopausal women free of mammary pathology, on the
      contrary, are composed of an epithelial cell population that is refractory to
      transformation, called Stem cells 2. It was further postulated that the degree of
      differentiation acquired through early pregnancy has changed the 'genomic
      signature' that differentiates Lob 1 of the early parous women from that of the
      nulliparous women by shifting the Stem cells 1 to Stem cells 2 that are
      refractory to carcinogenesis, making this the postulated mechanism of protection
      conferred by early full-term pregnancy. The identification of a putative breast
      stem cell (Stem cells 1) has, in the past decade, reached a significant impulse,
      and several markers also reported for other tissues have been found in the
      mammary epithelial cells of both rodents and humans. Although further work needs
      to be carried out in order to better understand the role of the Stem cells 2 and
      their interaction with the genes that confer them a specific signature,
      collectively the data presently available provide evidence that pregnancy,
      through the process of cell differentiation, shifts Stem cells 1 to Stem cells 2 
      cells that exhibit a specific genomic signature that could be responsible for
      the refractoriness of the mammary gland to carcinogenesis.

PMID- 15987444
TI  - Increased level of phosphorylated akt measured by chemiluminescence-linked
      immunosorbent assay is a predictor of poor prognosis in primary breast cancer
      overexpressing ErbB-2.
AB  - INTRODUCTION: Akt1, Akt2 and Akt3 kinases are downstream components of
      phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which
      influence cell growth, proliferation and survival. Akt2 overexpression and
      amplification have been described in breast, ovarian and pancreatic cancers. The
      present study was designed to investigate the prognostic significance of
      activated Akt in primary breast cancer and its association with other tumour
      biomarkers. METHODS: Using a two-site chemiluminescence-linked immunosorbent
      assay, we measured the quantitative expression levels of total phosphorylated (P
      S473) Akt (Akt1/Akt2/Akt3) on cytosol fractions obtained from fresh frozen tissue
      samples of 156 primary breast cancer patients. RESULTS: Akt phosphorylation was
      not associated with nodal status or ErbB-2 protein expression levels. High levels
      of phosphorylated Akt correlated (P < 0.01) with poor prognosis, and the
      significance of this correlation increased (P < 0.001) in the subset of patients
      with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to
      be associated with mRNA expression levels of several proliferation markers (e.g.
      thymidylate synthase), measured using quantitative real-time RT-PCR. CONCLUSION:
      Our findings demonstrate that, in breast cancer patients, Akt activation is
      associated with tumour proliferation and poor prognosis, particularly in the
      subset of patients with ErbB2-overexpressing tumours.

PMID- 15987445
TI  - Stromal cell derived factor-1: its influence on invasiveness and migration of
      breast cancer cells in vitro, and its association with prognosis and survival in
      human breast cancer.
AB  - INTRODUCTION: Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a
      member of the CXC subfamily of chemokines, which, through its cognate receptor
      (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer
      cells and in tumour metastasis. We conducted the present study to evaluate the
      effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we
      analyzed the expression of SDF-1 and its relation to clinicopathological features
      and clinical outcomes in human breast cancer. METHOD: Expression of SDF-1 mRNA in
      breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human
      breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with
      a SDF-1 expression vector, and their invasiveness and migration was tested in
      vitro. In addition, the expression of SDF-1 was investigated using
      immunohistochemistry and quantitative RT-PCR in samples of normal human mammary
      tissue (n = 32) and mammary tumour (n = 120). RESULTS: SDF-1 expression was
      identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression
      was detected in all cell lines and breast tissues. An autocrine loop was created
      following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1
      negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1+/+)
      or with control plasmid pcDNA4/GFP (MDA-MB-231+/-). MDA-MB-231SDF1+/+ cells
      exhibited significantly greater invasion and migration potential (in transfected
      cells versus in wild type and empty MDA-MB-231+/-; P < 0.01). In mammary tissues
      SDF-1 staining was primarily seen in stromal cells and weakly in mammary
      epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive
      than in node-negative tumours (P = 0.05), in tumours that metastasized (P =
      0.05), and tumours from patients who died (P = 0.03) than in tumours from
      patients who were disease free. It was most notable that levels of SDF-1
      correlated significantly with overall survival (P = 0.001) and incidence-free
      survival (P = 0.035). CONCLUSION: SDF-1 can increase the invasiveness and
      migration of breast cancer cells. Its levels correlated with node involvement and
      long-term survival in patients with breast cancer. SDF-1 may therefore have
      potential value in assessing clinical outcomes of patients with breast cancer.

PMID- 15987446
TI  - Overexpression of beta1-chain-containing laminins in capillary basement membranes
      of human breast cancer and its metastases.
AB  - INTRODUCTION: Laminins are the major components of vascular and parenchymal
      basement membranes. We previously documented a switch in the expression of
      vascular laminins containing the alpha4 chain from predominantly laminin-9
      (alpha4beta2gamma1) to predominantly laminin-8 (alpha4beta1gamma1) during
      progression of human brain gliomas to high-grade glioblastoma multiforme. Here,
      differential expression of laminins was studied in blood vessels and ductal
      epithelium of the breast. METHOD: In the present study the expressions of laminin
      isoforms alpha1-alpha5, beta1-beta3, gamma1, and gamma2 were examined during
      progression of breast cancer. Forty-five clinical samples of breast tissues
      including normal breast, ductal carcinomas in situ, invasive ductal carcinomas,
      and their metastases to the brain were compared using Western blot analysis and
      immunohistochemistry for various chains of laminin, in particular laminin-8 and
      laminin-9. RESULTS: Laminin alpha4 chain was observed in vascular basement
      membranes of most studied tissues, with the highest expression in metastases. At
      the same time, the expression of laminin beta2 chain (a constituent of laminin-9)
      was mostly seen in normal breast and carcinomas in situ but not in invasive
      carcinomas or metastases. In contrast, laminin beta1 chain (a constituent of
      laminin-8) was typically found in vessel walls of carcinomas and their metastases
      but not in those of normal breast. The expression of laminin-8 increased in a
      progression-dependent manner. A similar change was observed from laminin-11
      (alpha5beta2gamma1) to laminin-10 (alpha5beta1gamma1) during breast tumor
      progression. Additionally, laminin-2 (alpha2beta1gamma1) appeared in vascular
      basement membranes of invasive carcinomas and metastases. Chains of laminin-5
      (alpha3beta3gamma2) were expressed in the ductal epithelium basement membranes of
      the breast and diminished with tumor progression. CONCLUSION: These results
      suggest that laminin-2, laminin-8, and laminin-10 are important components of
      tumor microvessels and may associate with breast tumor progression. Angiogenic
      switch from laminin-9 and laminin-11 to laminin-8 and laminin-10 first occurs in
      carcinomas in situ and becomes more pronounced with progression of carcinomas to
      the invasive stage. Similar to high-grade brain gliomas, the expression of
      laminin-8 (and laminin-10) in breast cancer tissue may be a predictive factor for
      tumor neovascularization and invasion.

PMID- 15987447
TI  - Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2
      inhibitor celecoxib in human breast cancer cells.
AB  - INTRODUCTION: Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied
      as anticancer agents. In the present study we evaluated the mechanisms by which a
      highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two
      differentially invasive human breast cancer cell lines. METHODS: MDA-MB-231
      (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated
      with varying concentrations of celecoxib in vitro, and the effects of this agent
      on cell growth and angiogenesis were monitored by evaluating cell proliferation,
      apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of
      MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model.
      RESULTS: The highly invasive MDA-MB-231 cells express higher levels of COX-2 than
      do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2
      activity, indicated by prostaglandin E2 secretion, and caused significant growth
      arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells,
      the mechanism of celecoxib-induced growth arrest was by induction of apoptosis,
      associated with reduced activation of protein kinase B/Akt, and subsequent
      activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth
      arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib
      induced growth inhibition was reversed by addition of exogenous prostaglandin E2
      in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells
      formed significantly fewer extracellular matrix associated microvascular channels
      in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment
      not only inhibited cell growth and vascular channel formation but also reduced
      vascular endothelial growth factor levels. The in vitro findings corroborated in
      vivo data from a mouse xenograft model in which daily administration of celecoxib
      significantly reduced tumor growth of MDA-MB-231 cells, which was associated with
      reduced vascularization and increased necrosis in the tumor mass. CONCLUSION: The
      disparate molecular mechanisms of celecoxib-induced growth inhibition in human
      breast cancer cells depends upon the level of COX-2 expression and the invasive
      potential of the cell lines examined. Data suggest a role for COX-2 not only in
      the growth of cancer cells but also in activating the angiogenic pathway through
      regulating levels of vascular endothelial growth factor.

PMID- 15987448
TI  - Clinical utility of serum HER2/neu in monitoring and prediction of progression
      free survival in metastatic breast cancer patients treated with trastuzumab-based
      therapies.
AB  - INTRODUCTION: The purpose of this retrospective study was to determine the
      clinical utility of serum HER2/neu in monitoring metastatic breast cancer
      patients undergoing trastuzumab-based therapy and to compare these results with
      those obtained using cancer antigen (CA) 15-3. We also sought to determine
      whether early changes in serum HER2/neu concentrations could be a predictor of
      progression-free survival. METHODS: Sera were obtained retrospectively from 103
      women at four medical institutions. Patients eligible for participation were
      women with metastatic breast cancer who had HER2/neu tissue overexpression and
      were scheduled to be treated with trastuzumab with or without additional
      therapies as per the established practices of the treating physicians. A baseline
      serum sample for each patient was taken before trastuzumab-based therapy was
      started. Patients were subsequently monitored over 12 to 20 months and serum
      samples were taken at the time of clinical assessment and tested with Bayer's
      HER2/neu and CA15-3 assays. RESULTS: Concordance between clinical status in
      patients undergoing trastuzumab-based treatment and HER2/neu and CA15-3 used as
      single tests was 0.793 and 0.627, respectively, and increased to 0.829 when the
      tests were used in combination. Progression-free survival times did not differ
      significantly in patients with elevated baseline HER2/neu concentrations (> or =
      15 ng/mL) and those with normal concentrations (<15 ng/mL). However, progression
      free survival differed significantly (P = 0.043) according to whether the
      patient's HER2/neu concentration at 2 to 4 weeks after the start of therapy was
      >77% or < or = 77% of her baseline concentration. The median progression-free
      survival times for these two groups were 217 and 587 days, respectively. A
      similar trend was observed for a subcohort of patients treated specifically with
      a combination of trastuzumab and taxane. CONCLUSION: These findings indicate that
      serum HER2/neu testing is clinically valuable in monitoring metastatic breast
      cancer patients undergoing trastuzumab-based treatment and provides additional
      value over the commonly used CA15-3 test. The percentage of baseline HER2/neu
      concentrations in the early weeks after the start of therapy may be an early
      predictor of progression-free-survival.

PMID- 15987449
TI  - Bioluminescent human breast cancer cell lines that permit rapid and sensitive in
      vivo detection of mammary tumors and multiple metastases in immune deficient
      mice.
AB  - INTRODUCTION: Our goal was to generate xenograft mouse models of human breast
      cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide
      rapid mammary tumor growth; produce metastasis to clinically relevant tissues
      such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of
      both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two
      clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly
      luciferase were isolated following transfection of the parental cells with
      luciferase cDNA. Each subline was passaged once or twice in vivo to enhance
      primary tumor growth and to increase metastasis. The resulting luciferase
      expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent
      stability, primary tumor growth, and distal metastasis to lymph nodes, lungs,
      bone and soft tissues by bioluminescent imaging. Cells were injected into the
      mammary fat pad of nude and nude-beige mice or were delivered systemically via
      intracardiac injection. Metastasis was also evaluated by ex vivo imaging and
      histologic analysis postmortem. RESULTS: The D3H1 and D3H2LN cell lines exhibited
      long-term stable luciferase expression for up to 4-6 months of accumulative tumor
      growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad
      tumor development and detected early spontaneous lymph node metastasis in vivo.
      Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN
      tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected
      additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent
      histologic evaluation of tissue sections from lymph nodes and lung lobes
      confirmed spontaneous tumor metastasis at these sites. Following intracardiac
      injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal
      tissues, lymph nodes, brain and various visceral organs was detected. Weekly in
      vivo imaging data permitted longitudinal analysis of metastasis at multiple sites
      simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal
      and multiple soft tissue tumor metastasis. CONCLUSION: This study characterized
      two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with
      enhanced tumor growth and widespread metastasis in mice. Their application to
      current xenograft models of breast cancer offers rapid and highly sensitive
      detection options for preclinical assessment of anticancer therapies in vivo.

PMID- 15987450
TI  - CYP17 5'-UTR MspA1 polymorphism and the risk of premenopausal breast cancer in a
      German population-based case-control study.
AB  - INTRODUCTION: Studies on the association between the cytochrome P450c17alpha gene
      (CYP17) 5'-untranslated region MspA1 genetic polymorphism and breast cancer risk
      have yielded inconsistent results. Higher levels of estrogen have been reported
      among young nulliparous women with the A2 allele. Therefore we assessed the
      impact of CYP17 genotypes on the risk of premenopausal breast cancer, with
      emphasis on parity. METHODS: We used data from a population-based case-control
      study of women aged below 51 years conducted from 1992 to 1995 in Germany.
      Analyses were restricted to clearly premenopausal women with complete information
      on CYP17 and encompassed 527 case subjects and 904 controls, 99.5% of whom were
      of European descent. The MspA1 polymorphism was analyzed using PCR-RFLP (PCR
      restriction fragment length polymorphism) assay. RESULTS: The frequencies of the
      variant allele among the cases and controls were 43% and 41%, respectively.
      Overall, CYP17 A1/A2 and A2/A2 genotypes compared with the A1/A1 genotype were
      not associated with breast cancer, with adjusted odds ratios (ORs) of 1.04 and
      1.23, respectively. Among nulliparous women, however, breast cancer risk was
      elevated for the A1/A2 (OR = 1.31; 95% confidence interval (CI) 0.74 to 2.32) and
      the A2/A2 genotype (OR = 2.12; 95% CI 1.04 to 4.32) compared with the A1/A1
      genotype, with a trend towards increasing risk associated with number of A2
      alleles (P = 0.04). Otherwise, the CYP17 polymorphism was found neither to be an
      effect modifier of breast cancer risks nor to be associated with stage of
      disease. CONCLUSION: Our results do not indicate a major influence of CYP17 MspA1
      polymorphism on the risk of premenopausal breast cancer, but suggest that it may
      have an impact on breast cancer risk among nulliparous women. The finding,
      however, needs to be confirmed in further studies.

PMID- 15987451
TI  - Relationship of patients' age to histopathological features of breast tumours in
      BRCA1 and BRCA2 and mutation-negative breast cancer families.
AB  - INTRODUCTION: Our aim was to evaluate the relationship of patients' age to
      histopathological features of hereditary breast tumours in a series of breast
      cancer families not selected for age at diagnosis. In sporadic breast cancer,
      tumours from premenopausal patients have been shown to differ from those of
      postmenopausal patients, but this phenomenon has been little studied among
      familial patients. METHODS: Representative areas of all available breast cancer
      tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2, and 74 non-BRCA1/2 breast
      cancer families were punched into a tissue microarray. Immunohistochemical
      staining of oestrogen receptor, progesterone receptor, ERBB2, and p53 as well as
      the histology and grade of tumours in these three groups of families were studied
      in different age groups and compared with each other. RESULTS: We found that only
      breast cancers from young (<50 years) BRCA1+ patients represent features
      documented as being typical of BRCA1-associated cancers, such as high tumour
      grade, negativity for oestrogen and progesterone receptors, and overexpression of
      p53. Among the BRCA2 families, the opposite was found, with a significantly
      higher frequency of tumours negative for oestrogen and progesterone receptors
      among the older patients than among the other groups, but no distinctive tumour
      characteristics among the younger BRCA2 patients. CONCLUSION: Tumours of BRCA1
      and BRCA2 carriers aged 50 years or more differed significantly from those of
      younger carriers. This difference may reflect different biological behaviour and
      pathways of tumour development among the older and the younger BRCA1 and BRCA2
      patients, with impact also on prognosis and survival.

PMID- 15987453
TI  - Effects of milk fermented by Lactobacillus helveticus R389 on a murine breast
      cancer model.
AB  - INTRODUCTION: Antitumour activity is one of the health-promoting effects
      attributed to the lactic acid bacteria and their products of fermentation.
      Previous studies in mice demonstrated that bioactive compounds released in milk
      fermented by Lactobacillus helveticus R389 contribute to its immunoenhancing and
      antitumour properties. The aim of the present work was to study the effects of
      the consumption of milk fermented by L. helveticus R389 or its proteolytic
      deficient variant, L. helveticus L89, on a murine hormone-dependent breast cancer
      model. METHODS: Mice were fed with milk fermented by L. helveticus R389 or L.
      helveticus L89, during 2 or 7 days. The tumour control group received no special
      feeding. At the end of the feeding period, the mice were challenged by a
      subcutaneous injection of tumour cells in the mammary gland. Four days post
      injection, the mice received fermented milk on a cyclical basis. The rate of
      tumour development and the cytokines in serum, mammary gland tissue and tumour
      isolated cells were monitored. Bcl-2-positive cells in mammary glands and
      cellular apoptosis in tumour tissue were also studied. RESULTS: Seven days of
      cyclical administration of milk fermented by either bacterial strain delayed or
      stopped the tumour development. Cytokines demonstrated that L. helveticus R389
      modulated the immune response challenged by the tumour. IL-10 and IL-4 were
      increased in all the samples from this group. In comparison with the tumour
      control, all test groups showed a decrease of IL-6, a cytokine involved in
      oestrogen synthesis. Seven days of cyclical feeding with milk fermented by L.
      helveticus R389 produced an increase in the number of apoptotic cells, compared
      with all other groups. CONCLUSION: This study demonstrated that 7 days of
      cyclical administration of milk fermented by both strains of L. helveticus
      diminishes tumour growth, stimulating an antitumour immune response. Compounds
      released during milk fermentation with L. helveticus R389 would be implicated in
      its immunoregulatory capacity on the immune response in mammary glands and
      tumour, which were correlated with the cytokines found at the systemic level. The
      milk fermented by L. helveticus R389 was able to modulate the relationship
      between immune and endocrine systems (by IL-6 diminution), which is very
      important in oestrogen-dependent tumour and induced cellular apoptosis.

PMID- 15987452
TI  - Preventive and curative effect of melatonin on mammary carcinogenesis induced by
      dimethylbenz[a]anthracene in the female Sprague-Dawley rat.
AB  - INTRODUCTION: It has been well documented that the pineal hormone, melatonin,
      which plays a major role in the control of reproduction in mammals, also plays a
      role in the incidence and growth of breast and mammary cancer. The curative
      effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA
      induced) mammary adenocarcinoma (ADK) has been previously well documented in the
      female Sprague-Dawley rat. However, the preventive effect of melatonin in
      limiting the frequency of cancer initiation has not been well documented.
      METHODS: The aim of this study was to compare the potency of melatonin to limit
      the frequency of mammary cancer initiation with its potency to inhibit tumor
      progression once initiation, at 55 days of age, was achieved. The present study
      compared the effect of preventive treatment with melatonin (10 mg/kg daily)
      administered for only 15 days before the administration of DMBA with the effect
      of long-term (6-month) curative treatment with the same dose of melatonin
      starting the day after DMBA administration. The rats were followed up for a year
      after the administration of the DMBA. RESULTS: The results clearly showed almost
      identical preventive and curative effects of melatonin on the growth of DMBA
      induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory
      effects of melatonin. However, the mechanisms responsible for its strong
      preventive effect are still a matter of debate. At least, it can be envisaged
      that the artificial amplification of the intensity of the circadian rhythm of
      melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the
      frequency of cancer initiation. CONCLUSION: In view of the present results,
      obtained in the female Sprague-Dawley rat, it can be envisaged that the long-term
      inhibition of mammary ADK promotion by a brief, preventive treatment with
      melatonin could also reduce the risk of breast cancer induced in women by
      unidentified environmental factors.

PMID- 15987454
TI  - Designing a HER2/neu promoter to drive alpha1,3galactosyltransferase expression
      for targeted anti-alphaGal antibody-mediated tumor cell killing.
AB  - INTRODUCTION: Our goal was to specifically render tumor cells susceptible to
      natural cytolytic anti-alphaGal antibodies by using a murine
      alpha1,3galactosyltransferase (malphaGalT) transgene driven by a designed form of
      HER2/neu promoter (pNeu), the transcription of which is frequently observed to be
      above basal in breast tumors. Indeed, the alphaGalT activity that promotes
      Galalpha1,3Galbeta1,4GlcNAc-R (alphaGal) epitope expression has been mutationally
      disrupted during the course of evolution, starting from Old World primates, and
      this has led to the counter-production of large amounts of cytotoxic anti
      alphaGal antibodies in recent primates, including man. METHOD: Expression of the
      endogenous c-erbB-2 gene was investigated in various cell lines by northern
      blotting. A malphaGalT cDNA was constructed into pcDNA3 vector downstream of the
      original CMV promoter (pCMV/malphaGalT) and various forms of pNeu were prepared
      by PCR amplification and inserted in the pCMV/malphaGalT construct upstream of
      the malphaGalT cDNA, in the place of the CMV promoter. These constructs were
      transferred into HEK-293 control and breast tumor cell lines. Stably transfected
      cells were analyzed by northern blotting for their expression of alphaGalT and c
      erbB-2, and by flow cytometry for their binding with fluorescein isothiocyanate
      conjugated Griffonia simplicifolia/isolectin B4. RESULTS: We show that expression
      of the malphaGalT was up- or down-modulated according to the level of endogenous
      pNeu activity and the particular form of constructed pNeu. Among several
      constructs, two particular forms of the promoter, pNeu250 containing the CCAAT
      box and the PEA3 motif adjacent to the TATAA box, and pNeu664, which has three
      additional PEA3 motifs upstream of the CCAAT box, were found to promote
      differential alphaGalT expression. CONCLUSION: Our results strengthen current
      concepts about the crucial role played by the proximal PEA3 motif of pNeu, and
      may represent a novel therapeutic approach for the development of targeted
      transgene expression.

PMID- 15987455
TI  - Mutation analysis of the ATR gene in breast and ovarian cancer families.
AB  - INTRODUCTION: Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for
      only 20-30% of the familial aggregation of breast cancer, which suggests the
      involvement of additional susceptibility genes. The ATR (ataxia-telangiectasia-
      and Rad3-related) kinase is essential for the maintenance of genomic integrity.
      It functions both in parallel and cooperatively with ATM, but whereas ATM is
      primarily activated by DNA double-strand breaks induced by ionizing radiation,
      ATR has been shown to respond to a much broader range of DNA damage. Upon
      activation, ATR phosphorylates several important tumor suppressors, including
      p53, BRCA1 and CHK1. Based on its central function in the DNA damage response,
      ATR is a plausible candidate gene for susceptibility to cancer. METHODS: We
      screened the entire coding region of the ATR gene for mutations in affected index
      cases from 126 Finnish families with breast and/or ovarian cancer, 75 of which
      were classified as high-risk and 51 as moderate-risk families, by using
      conformation sensitive gel electrophoresis and direct sequencing. RESULTS: A
      large number of novel sequence variants were identified, four of which --
      Glu254Gly, Ser1142Gly, IVS24-48G>A and IVS26+15C>T -- were absent from the tested
      control individuals (n = 300). However, the segregation of these mutations with
      the cancer phenotype could not be confirmed, partly because of the lack of
      suitable DNA samples. CONCLUSION: The present study does not support a major role
      for ATR mutations in hereditary susceptibility to breast and ovarian cancer.

PMID- 15987456
TI  - TP53-binding protein variants and breast cancer risk: a case-control study.
AB  - INTRODUCTION: The TP53-binding protein (53BP1) has been shown to influence TP53
      mediated transcriptional activation, thus playing a pivotal role in DNA damage
      signalling. Genetic aberrations in TP53 and in ATM and CHEK2 predispose to
      cancer. We have therefore examined the effects of 53BP1 single nucleotide
      polymorphisms (D353E, G412S, and K1136Q) and the novel 53BP1 6bp deletion
      (1347_1352delTATCCC) on breast cancer risk. METHODS: Allelic discrimination was
      performed to investigate the frequencies of 53BP1 D353E, G412S, and K1136Q and of
      1347_1352delTATCCC in 353 patients with breast cancer and 960 control
      individuals. RESULTS: No significant association of 53BP1 D353E, G412S, or K1136Q
      with breast cancer risk was detected. 53BP1 1347_1352delTATCCC, leading to the
      loss of an isoleucine and a proline residue, showed a nonsignificant inverse
      association with breast cancer risk (odds ratio = 0.61, 95% confidence interval =
      0.22 to 1.68, P = 0.34). CONCLUSION: The lack of association casts doubt on the
      putative effects of D353E, G412S, and K1136Q on breast cancer risk. Investigating
      a larger study cohort might elucidate the influence of the 6bp deletion
      1347_1352delTATCCC. Studying the functional effect and the impact of this variant
      on the risk of other cancers may be revealing.

PMID- 15987457
TI  - Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast
      cancer risk and survival: the Shanghai Breast Cancer Study.
AB  - INTRODUCTION: Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme
      responsible for cleavage of plasminogen to angiotensin, which has an angiostatic
      effect. Using data from a population-based case-control study conducted among
      Chinese women in Shanghai, we evaluated the association of breast cancer risk and
      survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter
      region and A1082G in exon, resulting in an amino acid change of asparagine to
      serine. METHODS: Included in the study were 1,129 cases and 1,229 age-frequency
      matched population controls. Breast cancer patients were followed up to determine
      the intervals of overall survival and disease-free survival. RESULTS: The
      frequencies of the G allele in the A-82G and A1082G polymorphism among controls
      were 0.029 and 0.107, respectively. There were no associations between MMP12
      polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the
      A1082G polymorphism showed poorer overall survival (though the difference was not
      statistically significant) than patients with the AA genotype (hazard ratio 1.36,
      95% CI 0.92 to 2.00). CONCLUSION: This result suggests that MMP12 A1082G
      polymorphism may be related to prognosis in breast cancer patients. Additional
      studies with larger sample sizes are warranted.

PMID- 15987458
TI  - CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors:
      Australian Breast Cancer Family Study.
AB  - INTRODUCTION: Because CYP17 can influence the degree of exposure of breast
      tissues to oestrogen, the interaction between polymorphisms in this gene and
      hormonal risk factors is of particular interest. We attempted to replicate the
      findings of studies assessing such interactions with the -34T-->C polymorphism.
      METHODS: Risk factor and CYP17 genotyping data were derived from a large
      Australian population-based case-control-family study of 1,284 breast cancer
      cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95%
      confidence intervals (CIs) were calculated by unconditional logistic regression
      analyses. RESULTS: We found no associations between the CYP17 genotype and breast
      cancer overall. Premenopausal controls with A2/A2 genotype had a later age at
      menarche (P < 0.01). The only associations near statistical significance were
      that postmenopausal women with A1/A1 (wild-type) genotype had an increased risk
      of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95%
      CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59,
      95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other
      studies, and no evidence for interactions. CONCLUSION: We observed no evidence of
      effect modification of reproductive risk factors by CYP17 genotype, although the
      experiment did not have sufficient statistical power to detect small main effects
      and modest effects in subgroups. Associations found only in subgroup analyses
      based on relatively small numbers require cautious interpretation without
      confirmation by other studies. This emphasizes the need for replication in
      multiple and large population-based studies to provide convincing evidence for
      gene-environment interactions.

PMID- 15987459
TI  - Connexin 43 mediated gap junctional communication enhances breast tumor cell
      diapedesis in culture.
AB  - INTRODUCTION: Metastasis involves the emigration of tumor cells through the
      vascular endothelium, a process also known as diapedesis. The molecular
      mechanisms regulating tumor cell diapedesis are poorly understood, but may
      involve heterocellular gap junctional intercellular communication (GJIC) between
      tumor cells and endothelial cells. METHOD: To test this hypothesis we expressed
      connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and
      examined their ability to form gap junctions, establish heterocellular GJIC and
      migrate through monolayers of human microvascular endothelial cells (HMVEC) grown
      on matrigel-coated coverslips. RESULTS: HBL100 cells expressing Cx43 formed
      functional heterocellular gap junctions with HMVEC monolayers within 30 minutes.
      In addition, immunocytochemistry revealed Cx43 localized to contact sites between
      Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of
      diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing cells
      compared to empty vector control cells. The expression of a functionally inactive
      Cx43 chimeric protein in HBL100 cells failed to increase migration efficiency,
      suggesting that the observed up-regulation of diapedesis in Cx43 expressing cells
      required heterocellular GJIC. This finding is further supported by the
      observation that blocking homocellular and heterocellular GJIC with carbenoxolone
      in co-cultures also reduced diapedesis of Cx43 expressing HBL100 tumor cells.
      CONCLUSION: Collectively, our results suggest that heterocellular GJIC between
      breast tumor cells and endothelial cells may be an important regulatory step
      during metastasis.

PMID- 15987460
TI  - Menopausal hormone therapy after breast cancer: a meta-analysis and critical
      appraisal of the evidence.
AB  - INTRODUCTION: Menopausal hormone therapy (HT) is typically withheld from breast
      cancer survivors because of concerns about risk for recurrence. Our objectives
      were to estimate the effects of HT on recurrence in breast cancer survivors and
      to examine the reliability of these estimates. METHODS: In a systematic review of
      the literature we identified all reports of HT use in breast cancer survivors
      that included comparison groups. Study design features that might affect
      selection of participants, detection of recurrence, and manuscript publication
      were assessed. The relative risks for breast cancer recurrence associated with HT
      were combined with random effects models. RESULTS: Two randomized and eight
      observational studies included 1,316 breast cancer survivors who used HT and
      2,839 nonusers. In the observational studies, HT users were younger and more
      commonly node negative; only two reported balanced restaging for HT and control
      groups. Randomized trials suggest that HT increased the risk for recurrence
      (relative risk 3.41, 95% confidence interval 1.59-7.33), whereas observational
      studies suggest that HT decreased this risk (relative risk 0.64, 95% confidence
      interval 0.50-0.82). CONCLUSION: Results from observational studies of HT
      conducted in breast cancer survivors are discrepant with results from randomized
      trials. Observational studies of HT use in breast cancer survivors have design
      limitations that cannot be controlled for using standard statistical methods.
      Therefore, the randomized clinical trial data provide the only reliable estimates
      of the effect of HT use on recurrence risks in breast cancer survivors.

PMID- 15987461
TI  - Effect of reproductive factors on stage, grade and hormone receptor status in
      early-onset breast cancer.
AB  - INTRODUCTION: Women younger than 35 years who are diagnosed with breast cancer
      tend to have more advanced stage tumors and poorer prognoses than do older women.
      Pregnancy is associated with elevated exposure to estrogen, which may influence
      the progression of breast cancer in young women. The objective of the present
      study was to examine the relationship between reproductive events and tumor
      stage, grade, estrogen receptor and progesterone receptor status, and survival in
      women diagnosed with early-onset breast cancer. METHODS: In a population-based,
      case-case study of 254 women diagnosed with invasive breast cancer at age under
      35 years, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated
      using unconditional logistic regression with tumor characteristics as dependent
      variables and adjusting for age and education. Survival analyses also examined
      the relationship between reproductive events and overall survival. RESULTS:
      Compared with nulliparous women, women with three or more childbirths were more
      likely to be diagnosed with nonlocalized tumors (OR = 3.1, 95% CI = 1.3-7.7), and
      early age (<20 years) at first full-term pregnancy was also associated with a
      diagnosis of breast cancer that was nonlocalized (OR = 3.0, 95% CI = 1.2-7.4) and
      of higher grade (OR = 3.2, 95% CI 1.0-9.9). The hazard ratio for death among
      women with two or more full-term pregnancies, as compared with those with one
      full-term pregnancy or none, was 2.1 (95% CI = 1.0-4.5), adjusting for stage.
      Among parous women, those who lactated were at decreased risk for both estrogen
      receptor and progesterone receptor negative tumors (OR = 0.2, 95% CI = 0.1-0.5,
      and OR = 0.4, 95% CI = 0.2-0.8, respectively). CONCLUSION: The results of the
      present study suggest that pregnancy and lactation may influence tumor
      presentation and survival in women with early-onset breast cancer.

PMID- 15987462
TI  - Benign breast disease, recent alcohol consumption, and risk of breast cancer: a
      nested case-control study.
AB  - INTRODUCTION: Alcohol consumption is a well-established risk factor for breast
      cancer. Some studies have suggested that the risk of breast cancer associated
      with alcohol consumption is greater for women with a history of benign breast
      disease (BBD). We hypothesized that among women with biopsy-confirmed BBD, recent
      alcohol consumption would increase the risk of breast cancer in women with
      proliferative breast disease to a greater extent than in women with
      nonproliferative breast disease. METHODS: We conducted a nested case-control
      study in the Nurses' Health Study I and II. The cases (n = 282) were women
      diagnosed with incident breast cancer, with a prior biopsy-confirmed breast
      disease. The controls (n = 1,223) were participants with a previous BBD biopsy,
      but without a diagnosis of breast cancer. Pathologists reviewed benign breast
      biopsy slides in a blinded fashion and classified the BBD as nonproliferative,
      proliferative without atypia, or atypical hyperplasia, according to standard
      criteria. RESULTS: Women with nonproliferative breast disease consuming > or = 15
      g of alcohol per day had a nonsignificant 67% increased risk of breast cancer
      (odds ratio = 1.67; 95% confidence interval 0.65 to 4.34) compared with
      nondrinkers. There was no evidence that recent alcohol consumption increased the
      risk of breast cancer to a greater extent in women with proliferative BBD than
      among women with nonproliferative BBD (P for interactio n = 0.20). CONCLUSION:
      Contrary to our a priori hypothesis, there was no evidence that recent alcohol
      consumption increased the risk of breast cancer to a greater extent among women
      with proliferative BBD than among women with nonproliferative BBD.

PMID- 15987463
TI  - Alternative initiation and splicing in dicer gene expression in human breast
      cells.
AB  - INTRODUCTION: Dicer is a ribonuclease that mediates RNA interference both at the
      transcriptional and the post-transcriptional levels. Human dicer gene expression
      is regulated in different tissues. Dicer is responsible for the synthesis of
      microRNAs and short temporal (st)RNAs that regulate the expression of many genes.
      Thus, understanding the control of the expression of the dicer gene is essential
      for the appreciation of double-stranded (ds)RNA-mediated pathways of gene
      expression. Human dicer mRNA has many upstream open reading frames (uORFs) at the
      5'-leader sequences (the nucleotide sequence between the 5'-end and the start
      codon of the major ORF), and we studied whether these elements at the 5'-leader
      sequences regulate the expression of the dicer gene. METHOD: We determined the 5'
      leader sequences of the dicer mRNAs in human breast cells by 5'-RACE and S1
      nuclease protection analysis. We have analyzed the functions of the 5'-leader
      variants by reporter gene expression in vitro and in vivo. RESULTS: We found that
      the dicer transcripts in human breast cells vary in the sequence of their 5'
      leader sequences, and that alternative promoter selection along with alternative
      splicing of the 5'-terminal exons apparently generate these variations. The
      breast cell has at least two predominant forms of dicer mRNAs, one of which has
      an additional 110 nucleotides at the 5'-end. Sequence comparison revealed that
      the first 80 nucleotides of these mRNA isoforms are encoded by a new exon located
      approximately 16 kb upstream of the reported start site. There are 30 extra
      nucleotides added to the previously reported exon 1. The human breast cells
      studied predominantly express two 5'-leader variants of dicer mRNAs, one with the
      exons 2 and 3 (long form) and the other without them (short form). By reporter
      gene expression analysis we found that the exon 2 and 3 sequences at the 5'
      leader sequences are greatly inhibitory for the translation of the mRNA into
      protein. CONCLUSION: Dicer gene expression in human breast cells is regulated by
      alternative promoter selection to alter the length and composition of the 5'
      leader sequence of its mRNA. Furthermore, alternative splicing of its exon 2 and
      3 sequences of their pre-mRNA creates a more translationally competent mRNA in
      these cells.

PMID- 15987464
TI  - Inhibition of insulin-like growth factor-1 receptor signaling enhances growth
      inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer
      cells.
AB  - INTRODUCTION: Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase
      activity of the epidermal growth factor receptor (EGFR) and inhibits
      proliferation of several human cancer cell types including breast cancer. Phase
      II clinical trials with gefitinib monotherapy showed an objective response of 9
      to 19% in non-small-cell lung cancer patients and less than 10% for breast
      cancer, and phase III results have indicated no benefit of gefitinib in
      combination with chemotherapy over chemotherapy alone. In order to improve the
      antineoplastic activity of gefitinib, we investigated the effects of blocking the
      signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine
      kinase with a crucial role in malignancy that is coexpressed with EGFR in most
      human primary breast carcinomas. METHODS: AG1024 (an inhibitor of IGF-1R) was
      used with gefitinib for treatment of MDA468, MDA231, SK-BR-3, and MCF-7 breast
      cancer lines, which express similar levels of IGF-1R but varying levels of EGFR.
      Proliferation assays, apoptosis induction studies, and Western blot analyses were
      conducted with cells treated with AG1024 and gefitinib as single agents and in
      combination. RESULTS: Gefitinib and AG1024 reduced proliferation in all lines
      when used as single agents, and when used in combination revealed an additive-to
      synergistic effect on cell growth inhibition. Flow cytometry measurements of
      cells stained with annexin V-propidium iodide and cells stained for caspase-3
      activation indicated that adding an IGF-1R-targeting strategy to gefitinib
      results in higher levels of apoptosis than are achieved with gefitinib alone.
      Gefitinib either reduced or completely inhibited p42/p44 Erk kinase
      phosphorylation, depending on the cell line, while Akt phosphorylation was
      reduced by a combination of the two agents. Overexpression of IGF-1R in SK-BR-3
      cells was sufficient to cause a marked enhancement in gefitinib resistance.
      CONCLUSION: These results indicate that IGF-1R signaling reduces the
      antiproliferative effects of gefitinib in several breast cancer cell lines, and
      that the addition of an anti-IGF-1R strategy to gefitinib treatment may be more
      effective than a single-agent approach.

PMID- 15987465
TI  - Basal cytokeratins and their relationship to the cellular origin and functional
      classification of breast cancer.
AB  - Recent publications have classified breast cancers on the basis of expression of
      cytokeratin-5 and -17 at the RNA and protein levels, and demonstrated the
      importance of these markers in defining sporadic tumours with bad prognosis and
      an association with BRCA1-related breast cancers. These important observations
      using different technology platforms produce a new functional classification of
      breast carcinoma. However, it is important in developing hypotheses about the
      pathogenesis of this tumour type to review the nomenclature that is being used to
      emphasize potential confusion between terminology that defines clinical subgroups
      and markers of cell lineage. This article reviews the lineages in the normal
      breast in relation to what have become known as the 'basal-like' carcinomas.

PMID- 15987466
TI  - Imaging in breast cancer: Magnetic resonance spectroscopy.
AB  - A technique called in vivo magnetic resonance spectroscopy (MRS) can be performed
      along with magnetic resonance imaging (MRI) to obtain information about the
      chemical content of breast lesions. This information can be used for several
      clinical applications, such as monitoring the response to cancer therapies and
      improving the accuracy of lesion diagnosis. Initial MRS studies of breast cancer
      show promising results, and a growing number of research groups are incorporating
      the technique into their breast MRI protocols. This article introduces 1H-MRS of
      the breast, reviews the literature, discusses current methods and technical
      issues, and describes applications for treatment monitoring and lesion diagnosis.

PMID- 15987468
TI  - Estrogen-repressed genes -- key mediators of estrogen action?

PMID- 15987469
TI  - Accelerated partial breast irradiation: a valid choice.

PMID- 15987467
TI  - Imaging in breast cancer: Single-photon computed tomography and positron-emission
      tomography.
AB  - Although mammography remains a key imaging method for the early detection and
      screening of breast cancer, the overall accuracy of this test remains low.
      Several radiopharmaceuticals have been proposed as adjunct imaging methods to
      characterize breast masses by single-photon-emission computed tomography (SPECT)
      and positron-emission tomography (PET). Useful in characterizing indeterminate
      palpable masses and in the detection of axillary metastases, these techniques are
      insufficiently sensitive to detect subcentimetric tumor deposits. Their role in
      staging nodal involvement of the axillary areas therefore currently remains
      limited. Several enzymes and receptors have been targeted for imaging breast
      cancers with PET. [18F]fluorodeoxyglucose is particularly useful in the detection
      and staging of recurrent breast cancer and in assessing the response to
      chemotherapy. Several other ligands targeting proliferative activity, protein
      synthesis, and hormone and cell-membrane receptors may complement this approach
      by providing unique information about biological characteristics of breast cancer
      across primary and metastatic tumor sites.

PMID- 15987470
TI  - Laminin isoform expression in breast tumors.
AB  - Certain laminins of vascular basement membranes have been identified in human
      breast tumors and brain gliomas that share the same beta1 chain. These laminins
      are new carcinoma angiogenic markers and might represent potential targets for
      antiangiogenic therapy.

PMID- 15987471
TI  - Menopausal hormone therapy after breast cancer.
AB  - The use of postmenopausal hormone therapy after breast cancer remains
      controversial. Evidence shows variation by study design, and even among three
      randomized controlled trials there is substantial heterogeneity of results. Two
      Swedish trials of comparable size show relative risks of recurrence of 3.3 and
      0.82 on comparing women receiving postmenopausal hormone therapy with control
      women. The extent of use of tamoxifen and concomitant use of progestins in
      combination with estrogen, although raised as one possible explanation for this
      heterogeneity, are not supported by evidence from trials of high-dose progestins
      used after breast cancer. Caution is needed when considering the use of
      postmenopausal hormone therapy after breast cancer.

PMID- 15987472
TI  - Mammary epithelial cell transformation: insights from cell culture and mouse
      models.
AB  - Normal human mammary epithelial cells (HMECs) have a finite life span and do not
      undergo spontaneous immortalization in culture. Critical to oncogenic
      transformation is the ability of cells to overcome the senescence checkpoints
      that define their replicative life span and to multiply indefinitely -- a
      phenomenon referred to as immortalization. HMECs can be immortalized by exposing
      them to chemicals or radiation, or by causing them to overexpress certain
      cellular genes or viral oncogenes. However, the most efficient and reproducible
      model of HMEC immortalization remains expression of high-risk human
      papillomavirus (HPV) oncogenes E6 and E7. Cell culture models have defined the
      role of tumor suppressor proteins (pRb and p53), inhibitors of cyclin-dependent
      kinases (p16INK4a, p21, p27 and p57), p14ARF, telomerase, and small G proteins
      Rap, Rho and Ras in immortalization and transformation of HMECs. These cell
      culture models have also provided evidence that multiple epithelial cell subtypes
      with distinct patterns of susceptibility to oncogenesis exist in the normal
      mammary tissue. Coupled with information from distinct molecular portraits of
      primary breast cancers, these findings suggest that various subtypes of mammary
      cells may be precursors of different subtypes of breast cancers. Full oncogenic
      transformation of HMECs in culture requires the expression of multiple gene
      products, such as SV40 large T and small t, hTERT (catalytic subunit of human
      telomerase), Raf, phosphatidylinositol 3-kinase, and Ral-GEFs (Ral guanine
      nucleotide exchange factors). However, when implanted into nude mice these
      transformed cells typically produce poorly differentiated carcinomas and not
      adenocarcinomas. On the other hand, transgenic mouse models using ErbB2/neu, Ras,
      Myc, SV40 T or polyomavirus T develop adenocarcinomas, raising the possibility
      that the parental normal cell subtype may determine the pathological type of
      breast tumors. Availability of three-dimensional and mammosphere models has led
      to the identification of putative stem cells, but more studies are needed to
      define their biologic role and potential as precursor cells for distinct breast
      cancers. The combined use of transformation strategies in cell culture and mouse
      models together with molecular definition of human breast cancer subtypes should
      help to elucidate the nature of breast cancer diversity and to develop
      individualized therapies.

PMID- 15987473
TI  - Regeneration of the immunoglobulin heavy-chain repertoire after transient B-cell
      depletion with an anti-CD20 antibody.
AB  - B-cell depletive therapies have beneficial effects in patients suffering from
      rheumatoid arthritis. Nevertheless, the role of B cells in the pathogenesis of
      the disease is not clear. In particular, it is not known how the regeneration of
      the B-cell repertoire takes place. Two patients with active rheumatoid arthritis
      were treated with rituximab, and the rearranged immunoglobulin heavy-chain genes
      (Ig-VH) were analysed to follow the B-cell regeneration. Patient A was treated
      with two courses of rituximab, and B-cell regeneration was followed over 27
      months by analysing more than 680 Ig-VH sequences. Peripheral B-cell depletion
      lasted 7 months and 10 months, respectively, and each time was accompanied by a
      clinical improvement. Patient B received one treatment course. B-cell depletion
      lasted 5 months and was accompanied by a good clinical response. B cells
      regenerated well in both patients, and the repopulated B-cell repertoire was
      characterised by a polyclonal and diverse use of Ig-VH genes, as expected in
      adult individuals. During the early phase of B-cell regeneration we observed the
      expansion and recirculation of a highly mutated B-cell population. These cells
      expressed very different Ig-VH genes. They were class-switched and could be
      detected for a short period only. Patient A was followed long term, whereby some
      characteristic changes in the VH2 family as well as in specific mini-genes like
      VH3-23, VH 4-34 or VH 1-69 were observed. In addition, rituximab therapy resulted
      in the loss of clonal B cells for the whole period. Our data show that
      therapeutic transient B-cell depletion by anti-CD20 antibodies results in the
      regeneration of a diverse and polyclonal heavy-chain repertoire. During the early
      phase of B-cell regeneration, highly mutated B cells recirculate for a short time
      period in both the patients analysed. The longitudinal observation of a single
      patient up to 27 months shows subtle intraindividual changes, which may indicate
      repertoire modulation.

PMID- 15987474
TI  - Dynamic magnetic resonance of the wrist in psoriatic arthritis reveals imaging
      patterns similar to those of rheumatoid arthritis.
AB  - This dynamic magnetic resonance imaging (MRI) study is concerned with a
      prospective evaluation of wrist synovitis in patients with psoriatic arthritis
      (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy
      controls. Fifteen consecutive patients with PsA, 49 consecutive patients with RA,
      30 RA patients matched for disease severity with those with PsA, and 8 healthy
      controls were studied. MRI was performed with a low-field (0.2T), extremity
      dedicated machine. After an intravenous bolus injection of gadolinium
      diethylenetriaminepentaacetic acid, 20 consecutive fast spin-echo axial images of
      the wrist were obtained every 18 s. The enhancement ratio was calculated both as
      rate of early enhancement (REE), which shows the slope of the curve of contrast
      uptake per second during the first 55 s, and as relative enhancement (RE), which
      indicates the steady state of enhancement. The REE was 1.0 +/- 0.6 in patients
      with PsA, 1.6 +/- 0.7 in consecutive patients with RA, and 0.1 +/- 0.1 in
      controls (p <0.001). The RE was 87.1 +/- 39.2 in patients with PsA, 125.8 +/-
      48.0 in consecutive RA patients, and 15.5 +/- 19.2 in controls (p <0.001).
      However, the same figures in matched RA patients were 1.3 +/- 0.7 and 107.3 +/-
      48.2, respectively (not significant in comparison with PsA). Rheumatoid-like PsA
      and oligoarticular PsA did not differ from each other in terms of synovial
      enhancement. Dynamic MRI shows the same pattern of synovitis in patients with PsA
      and RA when the two groups are matched for disease severity. This technique
      cannot be used to differentiate PsA from RA. However, REE and RE were
      significantly higher in PsA than in normal controls, with only one instance of
      overlap between values found for the two groups.

PMID- 15987475
TI  - The role of interleukin-1 in the pathogenesis of human intervertebral disc
      degeneration.
AB  - In this study, we investigated the hypotheses that in human intervertebral disc
      (IVD) degeneration there is local production of the cytokine IL-1, and that this
      locally produced cytokine can induce the cellular and matrix changes of IVD
      degeneration. Immunohistochemistry was used to localize five members of the IL-1
      family (IL-1alpha, IL-1beta, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1
      receptor, type I), and ICE (IL-1beta-converting enzyme)) in non-degenerate and
      degenerate human IVDs. In addition, cells derived from non-degenerate and
      degenerate human IVDs were challenged with IL-1 agonists and the response was
      investigated using real-time PCR for a number of matrix-degrading enzymes, matrix
      proteins, and members of the IL-1 family. This study has shown that native disc
      cells from non-degenerate and degenerate discs produced the IL-1 agonists,
      antagonist, the active receptor, and IL-1beta-converting enzyme. In addition,
      immunopositivity for these proteins, with the exception of IL-1Ra, increased with
      severity of degeneration. We have also shown that IL-1 treatment of human IVD
      cells resulted in increased gene expression for the matrix-degrading enzymes (MMP
      3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS
      4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a
      decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen
      I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate
      IVD. It is synthesized by native disc cells, and treatment of human disc cells
      with IL-1 induces an imbalance between catabolic and anabolic events, responses
      that represent the changes seen during disc degeneration. Therefore, inhibiting
      IL-1 could be an important therapeutic target for preventing and reversing disc
      degeneration.

PMID- 15987476
TI  - Serum protein profile in systemic-onset juvenile idiopathic arthritis
      differentiates response versus nonresponse to therapy.
AB  - Systemic-onset juvenile idiopathic arthritis (SJIA) is a disease of unknown
      etiology with an unpredictable response to treatment. We examined two groups of
      patients to determine whether there are serum protein profiles reflective of
      active disease and predictive of response to therapy. The first group (n = 8)
      responded to conventional therapy. The second group (n = 15) responded to an
      experimental antibody to the IL-6 receptor (MRA). Paired sera from each patient
      were analyzed before and after treatment, using surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Despite
      the small number of patients, highly significant and consistent differences were
      observed before and after response to therapy in all patients. Of 282 spectral
      peaks identified, 23 had mean signal intensities significantly different (P <
      0.001) before treatment and after response to treatment. The majority of these
      differences were observed regardless of whether patients responded to
      conventional therapy or to MRA. These peaks represent potential biomarkers of
      active disease. One such peak was identified as serum amyloid A, a known acute
      phase reactant in SJIA, validating the SELDI-TOF MS platform as a useful
      technology in this context. Finally, profiles from serum samples obtained at the
      time of active disease were compared between the two patient groups. Nine peaks
      had mean signal intensities significantly different (P < 0.001) between active
      disease in patients who responded to conventional therapy and in patients who
      failed to respond, suggesting a possible profile predictive of response.
      Collectively, these data demonstrate the presence of serum proteomic profiles in
      SJIA that are reflective of active disease and suggest the feasibility of using
      the SELDI-TOF MS platform used as a tool for proteomic profiling and discovery of
      novel biomarkers in autoimmune diseases.

PMID- 15987477
TI  - Chondrocytes, synoviocytes and dermal fibroblasts all express PH-20, a
      hyaluronidase active at neutral pH.
AB  - Hyaluronan (HA), an important component of connective tissues, is highly
      metabolically active, but the mechanisms involved in its catabolism are still
      largely unknown. We hypothesized that a protein similar to sperm PH-20, the only
      mammalian hyaluronidase known to be active at neutral pH, could be expressed in
      connective tissue cells. An mRNA transcript similar to that of PH-20 was found in
      chondrocytes, synoviocytes, and dermal fibroblasts, and its levels were enhanced
      upon stimulation with IL-1. In cell layers extracted with Triton X-100 - but not
      with octylglucoside - and in culture media, a polyclonal antipeptide anti-PH-20
      antibody identified protein bands with a molecular weight similar to that of
      sperm PH-20 (60 to 65 kDa) and exhibiting a hyaluronidase activity at neutral pH.
      Further, upon stimulation with IL-1, the amounts of the neutral-active
      hyaluronidase increased in both cell layers and culture media. These findings
      contribute potential important new insights into the biology of connective
      tissues. It is likely that PH-20 facilitates cell-receptor-mediated uptake of HA,
      while overexpression or uncontrolled expression of the enzyme can cause great
      havoc to connective tissues: not only does HA fragmentation compromise the
      structural integrity of tissues, but also the HA fragments generated are highly
      angiogenic and are potent inducers of proinflammatory cytokines. On the other
      hand, the enzyme activity may account for the progressive depletion of HA seen in
      osteoarthritis cartilage, a depletion that is believed to play an important role
      in the apparent irreversibility of this disease process.

PMID- 15987478
TI  - A monoclonal antibody against kininogen reduces inflammation in the HLA-B27
      transgenic rat.
AB  - The human leukocyte antigen B27 (HLA-B27) transgenic rat is a model of human
      inflammatory bowel disease, rheumatoid arthritis and psoriasis. Studies of
      chronic inflammation in other rat models have demonstrated activation of the
      kallikrein-kinin system as well as modulation by a plasma kallikrein inhibitor
      initiated before the onset of clinicopathologic changes or a deficiency in high
      molecular-mass kininogen. Here we study the effects of monoclonal antibody C11C1,
      an antibody against high-molecular-mass kininogen that inhibits the binding of
      high-molecular-mass kininogen to leukocytes and endothelial cells in the HLA-B27
      rat, which was administered after the onset of the inflammatory changes. Thrice
      weekly intraperitoneal injections of monoclonal antibody C11C1 or isotype IgG1
      were given to male 23-week-old rats for 16 days. Stool character as a measure of
      intestinal inflammation, and the rear limbs for clinical signs of arthritis
      (tarsal joint swelling and erythema) were scored daily. The animals were killed
      and the histology sections were assigned a numerical score for colonic
      inflammation, synovitis, and cartilage damage. Administration of monoclonal C11C1
      rapidly decreased the clinical scores of pre-existing inflammatory bowel disease
      (P < 0.005) and arthritis (P < 0.001). Histological analyses confirmed
      significant reductions in colonic lesions (P = 0.004) and synovitis (P = 0.009).
      Decreased concentrations of plasma prekallikrein and high-molecular-mass
      kininogen were found, providing evidence of activation of the kallikrein-kinin
      system. The levels of these biomarkers were reversed by monoclonal antibody
      C11C1, which may have therapeutic potential in human inflammatory bowel disease
      and arthritis.

PMID- 15987479
TI  - Mithramycin downregulates proinflammatory cytokine-induced matrix
      metalloproteinase gene expression in articular chondrocytes.
AB  - Interleukin-1 (IL-1), IL-17 and tumor necrosis factor alpha (TNF-alpha) are the
      main proinflammatory cytokines implicated in cartilage breakdown by matrix
      metalloproteinase (MMPs) in arthritic joints. We studied the impact of an anti
      neoplastic antibiotic, mithramycin, on the induction of MMPs in chondrocytes. MMP
      3 and MMP-13 gene expression induced by IL-1beta, TNF-alpha and IL-17 was
      downregulated by mithramycin in human chondrosarcoma SW1353 cells and in primary
      human and bovine femoral head chondrocytes. Constitutive and IL-1-stimulated MMP
      13 levels in bovine and human cartilage explants were also suppressed.
      Mithramycin did not significantly affect the phosphorylation of the mitogen
      activated protein kinases, extracellular signal-regulated kinase, p38 and c-Jun N
      terminal kinase. Despite effective inhibition of MMP expression by mithramycin
      and its potential to reduce cartilage degeneration, the agent might work through
      multiple unidentified mechanisms.

PMID- 15987480
TI  - Early rheumatoid arthritis is characterized by a distinct and transient synovial
      fluid cytokine profile of T cell and stromal cell origin.
AB  - Pathological processes involved in the initiation of rheumatoid synovitis remain
      unclear. We undertook the present study to identify immune and stromal processes
      that are present soon after the clinical onset of rheumatoid arthritis (RA) by
      assessing a panel of T cell, macrophage, and stromal cell related cytokines and
      chemokines in the synovial fluid of patients with early synovitis. Synovial fluid
      was aspirated from inflamed joints of patients with inflammatory arthritis of
      duration 3 months or less, whose outcomes were subsequently determined by follow
      up. For comparison, synovial fluid was aspirated from patients with acute crystal
      arthritis, established RA and osteoarthritis. Rheumatoid factor activity was
      blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines
      measured using a multiplex based system. Patients with early inflammatory
      arthritis who subsequently developed RA had a distinct but transient synovial
      fluid cytokine profile. The levels of a range of T cell, macrophage and stromal
      cell related cytokines (e.g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast
      growth factor and epidermal growth factor) were significantly elevated in these
      patients within 3 months after symptom onset, as compared with early arthritis
      patients who did not develop RA. In addition, this profile was no longer present
      in established RA. In contrast, patients with non-rheumatoid persistent synovitis
      exhibited elevated levels of interferon-gamma at initiation. Early synovitis
      destined to develop into RA is thus characterized by a distinct and transient
      synovial fluid cytokine profile. The cytokines present in the early rheumatoid
      lesion suggest that this response is likely to influence the microenvironment
      required for persistent RA.

PMID- 15987481
TI  - Acute phase reactants add little to composite disease activity indices for
      rheumatoid arthritis: validation of a clinical activity score.
AB  - INTRODUCTION: Frequent assessments of rheumatoid arthritis (RA) disease activity
      allow timely adaptation of therapy, which is essential in preventing disease
      progression. However, values of acute phase reactants (APRs) are needed to
      calculate current composite activity indices, such as the Disease Activity Score
      (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of
      erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI).
      We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI
      modification eliminating APRs - termed the Clinical Disease Activity Index (CDAI;
      i.e. the sum of tender and swollen joint counts [28 joints] and patient and
      physician global assessments [in cm]) - would have comparable validity in
      clinical cohorts. METHOD: Data sources comprised an observational cohort of 767
      RA patients (average disease duration 8.1 +/- 10.6 years), and an independent
      inception cohort of 106 patients (disease duration 11.5 +/- 12.5 weeks) who were
      followed prospectively. RESULTS: Our clinically based hypothesis was
      statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of
      the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with
      DAS28 (R = 0.89-0.90) and comparably to the correlation of SDAI with DAS28 (R =
      0.90-0.91). In additional analyses, the CDAI when compared to the SDAI and the
      DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably
      to the agreement between DAS28 and DAS28-CRP. All three scores correlated
      similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45-0.47). The
      average changes in all scores were greater in patients with better American
      College of Rheumatology response (P < 0.0001, analysis of variance; discriminant
      validity). All scores exhibited similar correlations with radiological
      progression (construct validity) over 3 years (R = 0.54-0.58; P < 0.0001).
      CONCLUSION: APRs add little information on top (and independent) of the
      combination of clinical variables included in the SDAI. A purely clinical score
      is a valid measure of disease activity and will have its greatest merits in
      clinical practice rather than research, where APRs are usually always available.
      The CDAI may facilitate immediate and consistent treatment decisions and help to
      improve patient outcomes in the longer term.

PMID- 15987482
TI  - The differential contribution of tumour necrosis factor to thermal and mechanical
      hyperalgesia during chronic inflammation.
AB  - Therapies directed against tumour necrosis factor (TNF) are effective for the
      treatment of rheumatoid arthritis and reduce pain scores in this condition. In
      this study, we sought to explore mechanisms by which TNF contributes to
      inflammatory pain in an experimental model of arthritis. The effects of an anti
      TNF agent, etanercept, on behavioural pain responses arising from rat
      monoarthritis induced by complete Freund's adjuvant were assessed and compared
      with expression of TNF receptors (TNFRs) by dorsal root ganglion (DRG) cells at
      corresponding time points. Etanercept had no effect on evoked pain responses in
      normal animals but exerted a differential effect on the thermal and mechanical
      hyperalgesia associated with rat arthritis induced by complete Freund's adjuvant
      (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2
      expression on DRG cells, which was maintained throughout the time course of the
      model. TNFR1 expression was increased in neuronal cells of the DRG bilaterally
      after arthritis induction. In contrast, TNFR2 expression occurred exclusively on
      non-neuronal cells of the macrophage-monocyte lineage, with cell numbers
      increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong
      correlation was observed between numbers of macrophages and the development of
      mechanical hyperalgesia in CFA-induced arthritis. These results highlight the
      potential for TNF to play a vital role in inflammatory hyperalgesia, both by a
      direct action on neurons via TNFR1 and by facilitating the accumulation of
      macrophages in the DRG via a TNFR2-mediated pathway.

PMID- 15987483
TI  - Decreased levels of soluble receptor for advanced glycation end products in
      patients with rheumatoid arthritis indicating deficient inflammatory control.
AB  - The receptor for advanced glycation end products (RAGE) is a member of the
      immunoglobulin superfamily being expressed as a cell surface molecule and binding
      a variety of ligands. One of these ligands is high-mobility group box chromosomal
      protein 1, a potent proinflammatory cytokine, expression of which is increased in
      synovial tissue and in synovial fluid of rheumatoid arthritis (RA) patients. The
      interaction of high-mobility group box chromosomal protein 1 with cell-surface
      RAGE leads to an inflammatory response. In contrast, the presence of soluble RAGE
      (sRAGE) may abrogate cellular activation since the ligand is bound prior to
      interaction with the surface receptor. Our aim was to analyse to what extent
      sRAGE is present in patients with chronic joint inflammation (RA) as compared
      with patients with non-inflammatory joint disease and with healthy subjects, and
      to assess whether there is an association between sRAGE levels and disease
      characteristics. Matching samples of blood and synovial fluid were collected from
      62 patients with RA with acute joint effusion. Blood from 45 healthy individuals,
      synovial fluid samples from 33 patients with non-inflammatory joint diseases and
      blood from six patients with non-inflammatory joint diseases were used for
      comparison. sRAGE levels were analysed using an ELISA.RA patients displayed
      significantly decreased blood levels of sRAGE (871 +/- 66 pg/ml, P < 0.0001) as
      compared with healthy controls (1290 +/- 78 pg/ml) and with patients with non
      inflammatory joint disease (1569 +/- 168 pg/ml). Importantly, sRAGE levels in the
      synovial fluid of RA patients (379 +/- 36 pg/ml) were lower than in corresponding
      blood samples and correlated significantly with blood sRAGE. Interestingly, a
      significantly higher sRAGE level was found in synovial fluid of RA patients
      treated with methotrexate as compared with patients without disease-modifying
      anti-rheumatic treatment.We conclude that a decreased level of sRAGE in patients
      with RA might increase the propensity towards inflammation, whereas treatment
      with methotrexate counteracts this feature.

PMID- 15987484
TI  - Characterization of histopathology and gene-expression profiles of synovitis in
      early rheumatoid arthritis using targeted biopsy specimens.
AB  - The disease category of early rheumatoid arthritis (RA) has been limited with
      respect to clinical criteria. Pathological manifestations of synovitis in
      patients whose disease is clinically classified as early RA seem to be
      heterogeneous, with regular variations. To clarify the relation between the
      molecular and histopathological features of the synovitis, we analyzed gene
      expression profiles in the synovial lining tissues to correlate them with
      histopathological features. Synovial tissues were obtained from knee joints of 12
      patients with early RA by targeted biopsy under arthroscopy. Surgical specimens
      of long-standing RA (from four patients) were examined as positive controls. Each
      histopathological parameter characteristic of rheumatoid synovitis in synovial
      tissues was scored under light microscopy. Total RNAs from synovial lining
      tissues were obtained from the specimens selected by laser capture
      microdissection and the mRNAs were amplified by bacteriophage T7 RNA polymerase.
      Their cDNAs were analyzed in a cDNA microarray with 23,040 cDNAs, and the levels
      of gene expression in multilayered lining tissues, compared with those of normal
      like lining tissues in specimens from the same person, were determined to
      estimate gene-expression profiles characteristic of the synovial proliferative
      lesions in each case. Based on cluster analysis of all cases, gene-expression
      profiles in the lesions in early RA fell into two groups. The groups had
      different expression levels of genes critical for proliferative inflammation,
      including those encoding cytokines, adhesion molecules, and extracellular
      matrices. One group resembled synovitis in long-standing RA and had high scores
      for some histopathological features - involving accumulations of lymphocytes and
      plasma cells - but not for other features. Possible differences in the
      histopathogenesis and prognosis of synovitis between the two groups are discussed
      in relation to the candidate genes and histopathology.

PMID- 15987486
TI  - Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes.
AB  - Somatic mutations have a role in the pathogenesis of a number of diseases,
      particularly cancers. Here we present data supporting a role of mitochondrial
      somatic mutations in an autoimmune disease, rheumatoid arthritis (RA). RA is a
      complex, multifactorial disease with a number of predisposition traits, including
      major histocompatibility complex (MHC) type and early bacterial infection in the
      joint. Somatic mutations in mitochondrial peptides displayed by MHCs may be
      recognized as non-self, furthering the destructive immune infiltration of the RA
      joint. Because many bacterial proteins have mitochondrial homologues, the immune
      system may be primed against these altered peptides if they mimic bacterial
      homologues. In addition, somatic mutations may be influencing cellular function,
      aiding in the acquirement of transformed properties of RA synoviocytes. To test
      the hypothesis that mutations in mitochondrial DNA (mtDNA) are associated with
      RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH dehydrogenase
      1 (subunit one of complex I - NADH dehydrogenase) of synoviocyte mitochondria
      from RA patients, using tissue from osteoarthritis (OA) patients for controls. We
      identified the mutational burden and amino acid changes in potential epitope
      regions in the two patient groups. RA synoviocyte mtDNA had about twice the
      number of mutations as the OA group. Furthermore, some of these changes had
      resulted in potential non-self MHC peptide epitopes. These results provide
      evidence for a new role for somatic mutations in mtDNA in RA and predict a role
      in other diseases.

PMID- 15987485
TI  - Osteoporosis in experimental postmenopausal polyarthritis: the relative
      contributions of estrogen deficiency and inflammation.
AB  - Generalized osteoporosis in postmenopausal rheumatoid arthritis (RA) is caused
      both by estrogen deficiency and by the inflammatory disease. The relative
      importance of each of these factors is unknown. The aim of this study was to
      establish a murine model of osteoporosis in postmenopausal RA, and to evaluate
      the relative importance and mechanisms of menopause and arthritis-related
      osteoporosis. To mimic postmenopausal RA, DBA/1 mice were ovariectomized,
      followed by the induction of type II collagen-induced arthritis. After the mice
      had been killed, paws were collected for histology, one femur for bone mineral
      density (BMD) and sera for analyses of markers of bone resorption (RatLaps; type
      I collagen cross-links, bone formation (osteocalcin) and cartilage destruction
      (cartilage oligomeric matrix protein), and for the evaluation of antigen-specific
      and innate immune responsiveness. Ovariectomized mice displayed more severe
      arthritis than sham-operated controls. At termination of the experiment,
      arthritic control mice and non-arthritic ovariectomized mice displayed trabecular
      bone losses of 26% and 22%, respectively. Ovariectomized mice with arthritis had
      as much as 58% decrease in trabecular BMD. Interestingly, cortical BMD was
      decreased by arthritis but was not affected by hormonal status. In addition,
      markers of bone resorption and cartilage destruction were increased in arthritic
      mice, whereas markers of bone formation were increased in ovariectomized mice.
      This study demonstrates that the loss of endogenous estrogen and inflammation
      contribute additively and equally to osteoporosis in experimental postmenopausal
      polyarthritis. Markers of bone remodeling and bone marrow lymphocyte phenotypes
      indicate different mechanisms for the development of osteoporosis caused by
      ovariectomy and arthritis in this model.

PMID- 15987487
TI  - Regional assessment of articular cartilage gene expression and small proteoglycan
      metabolism in an animal model of osteoarthritis.
AB  - Osteoarthritis (OA), the commonest form of arthritis and a major cause of
      morbidity, is characterized by progressive degeneration of the articular
      cartilage. Along with increased production and activation of degradative enzymes,
      altered synthesis of cartilage matrix molecules and growth factors by resident
      chondrocytes is believed to play a central role in this pathological process. We
      used an ovine meniscectomy model of OA to evaluate changes in chondrocyte
      expression of types I, II and III collagen; aggrecan; the small leucine-rich
      proteoglycans (SLRPs) biglycan, decorin, lumican and fibromodulin; transforming
      growth factor-beta; and connective tissue growth factor. Changes were evaluated
      separately in the medial and lateral tibial plateaux, and were confirmed for
      selected molecules using immunohistochemistry and Western blotting. Significant
      changes in mRNA levels were confined to the lateral compartment, where active
      cartilage degeneration was observed. In this region there was significant
      upregulation in expession of types I, II and III collagen, aggrecan, biglycan and
      lumican, concomitant with downregulation of decorin and connective tissue growth
      factor. The increases in type I and III collagen mRNA were accompanied by
      increased immunostaining for these proteins in cartilage. The upregulated lumican
      expression in degenerative cartilage was associated with increased lumican core
      protein deficient in keratan sulphate side-chains. Furthermore, there was
      evidence of significant fragmentation of SLRPs in both normal and arthritic
      tissue, with specific catabolites of biglycan and fibromodulin identified only in
      the cartilage from meniscectomized joints. This study highlights the focal nature
      of the degenerative changes that occur in OA cartilage and suggests that altered
      synthesis and proteolysis of SLRPs may play an important role in cartilage
      destruction in arthritis.

PMID- 15987488
TI  - Reliability of computerized image analysis for the evaluation of serial synovial
      biopsies in randomized controlled trials in rheumatoid arthritis.
AB  - Analysis of biomarkers in synovial tissue is increasingly used in the evaluation
      of new targeted therapies for patients with rheumatoid arthritis (RA). This study
      determined the intrarater and inter-rater reliability of digital image analysis
      (DIA) of synovial biopsies from RA patients participating in clinical trials.
      Arthroscopic synovial biopsies were obtained before and after treatment from 19
      RA patients participating in a randomized controlled trial with prednisolone.
      Immunohistochemistry was used to detect CD3+ T cells, CD38+ plasma cells and
      CD68+ macrophages. The mean change in positive cells per square millimetre for
      each marker was determined by different operators and at different times using
      DIA. Nonparametric tests were used to determine differences between observers and
      assessments, and to determine changes after treatment. The intraclass
      correlations (ICCs) were calculated to determine the intrarater and inter-rater
      reliability. Intrarater ICCs showed good reliability for measuring changes in T
      lymphocytes (R = 0.87), plasma cells (R = 0.62) and macrophages (R = 0.73).
      Analysis by Bland-Altman plots showed no systemic differences between
      measurements. The smallest detectable changes were calculated and their
      discriminatory power revealed good response in the prednisolone group compared
      with the placebo group. Similarly, inter-rater ICCs also revealed good
      reliability for measuring T lymphocytes (R = 0.68), plasma cells (R = 0.69) and
      macrophages (R = 0.72). All measurements identified the same cell types as
      changing significantly in the treated patients compared with the placebo group.
      The measurement of change in total positive cell numbers in synovial tissue can
      be determined reproducibly for various cell types by DIA in RA clinical trials.

PMID- 15987489
TI  - Gene expression profile and synovial microcirculation at early stages of collagen
      induced arthritis.
AB  - A better understanding of the initial mechanisms that lead to arthritic disease
      could facilitate development of improved therapeutic strategies. We characterized
      the synovial microcirculation of knee joints in susceptible mouse strains
      undergoing intradermal immunization with bovine collagen II in complete Freund's
      adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible
      DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA
      resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo
      fluorescence microscopy of knee joints revealed marked leucocyte activation and
      interaction with the endothelial lining of synovial microvessels. This initial
      inflammatory cell response correlated with the gene expression profile at this
      disease stage. The majority of the 655 differentially expressed genes belonged to
      classes of genes that are involved in cell movement and structure, cell cycle and
      signal transduction, as well as transcription, protein synthesis and metabolism.
      However, 24 adhesion molecules and chemokine/cytokine genes were identified, some
      of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic
      factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand
      27 and IL-13 receptor alpha1). Online in vivo data on synovial tissue
      microcirculation, together with gene expression profiling, emphasize the
      potential role played by early inflammatory events in the development of
      arthritis.

PMID- 15987490
TI  - Perforin deficiency attenuates collagen-induced arthritis.
AB  - Collagen-induced arthritis (CIA), an approved animal model for rheumatoid
      arthritis, is thought to be a T cell-dependent disease. There is evidence that
      CD8+ T cells are a major subset controlling the pathogenesis of CIA. They
      probably contribute to certain features of disease, namely tissue destruction and
      synovial hyperplasia. In this study we examined the role of perforin (pfp), a key
      molecule of the cytotoxic death pathway that is expressed mainly in CD8+ T cells,
      for the pathogenesis of CIA. We generated DBA/1J mice suffering from mutations of
      the pfp molecule, DBA/1J-pfp-/-, and studied their susceptibility to arthritis.
      As a result, pfp-deficient mice showed a reduced incidence (DBA/1J-pfp+/+, 64%;
      DBA/1J-pfp-/-, 54%), a slightly delayed onset (onset of disease: DBA/1J-pfp+/+,
      53 +/- 3.6; DBA/1J-pfp-/-, 59 +/- 4.9 (mean +/- SEM), and milder form of the
      disease (maximum disease score: DBA/1J-pfp+/+, 7.3 +/- 1.1; DBA/1J-pfp-/-, 3.4 +/
      1.4 (mean +/- SEM); P < 0.05). Concomitantly, peripheral T cell proliferation in
      response to the specific antigen bovine collagen II was increased in pfp-/- mice
      compared with pfp+/+ mice, arguing for an impaired killing of autoreactive T
      cells caused by pfp deficiency. Thus, pfp-mediated cytotoxicity is involved in
      the initiation of tissue damage in arthritis, but pfp-independent cytotoxic death
      pathways might also contribute to CIA.

PMID- 15987491
TI  - NADPH-oxidase-driven oxygen radical production determines chondrocyte death and
      partly regulates metalloproteinase-mediated cartilage matrix degradation during
      interferon-gamma-stimulated immune complex arthritis.
AB  - In previous studies we have found that FcgammaRI determines chondrocyte death and
      matrix metalloproteinase (MMP)-mediated cartilage destruction during IFN-gamma
      regulated immune complex arthritis (ICA). Binding of immune complexes (ICs) to
      FcgammaRI leads to the prominent production of oxygen radicals. In the present
      study we investigated the contribution of NADPH-oxidase-driven oxygen radicals to
      cartilage destruction by using p47phox-/- mice lacking a functional NADPH oxidase
      complex. Induction of a passive ICA in the knee joints of p47phox-/- mice
      resulted in a significant elevation of joint inflammation at day 3 when compared
      with wild-type (WT) controls as studied by histology. However, when IFN-gamma was
      overexpressed by injection of adenoviral IFN-gamma in the knee joint before ICA
      induction, a similar influx of inflammatory cells was found at days 3 and 7,
      comprising mainly macrophages in both mouse strains. Proteoglycan depletion from
      the cartilage layers of the knee joints in both groups was similar at days 3 and
      7. Aggrecan breakdown in cartilage caused by MMPs was further studied by
      immunolocalisation of MMP-mediated neoepitopes (VDIPEN). VDIPEN expression in the
      cartilage layers of arthritic knee joints was markedly lower (between 30 and 60%)
      in IFN-gamma-stimulated arthritic p47phox-/- mice at day 7 than in WT controls,
      despite significant upregulation of mRNA levels of various MMPs such as MMP-3,
      MMP-9, MMP-12 and MMP-13 in synovia and MMP-13 in cartilage layers as measured
      with quantitative RT-PCR. The latter observation suggests that oxygen radicals
      are involved in the activation of latent MMPs. Chondrocyte death, determined as
      the percentage of empty lacunae in articular cartilage, ranged between 20 and 60%
      at day 3 and between 30 and 80% at day 7 in WT mice, and was completely blocked
      in p47phox-/- mice at both time points. FcgammaRI mRNA expression was
      significantly lower, and FcgammaRII and FcgammaRIII were higher, in p47phox-/-
      mice than in controls. NADPH-oxidase-driven oxygen radical production determines
      chondrocyte death and aggravates MMP-mediated cartilage destruction during IFN
      gamma-stimulated IC-mediated arthritis. Upregulation of FcgammaRI by oxygen
      radicals may contribute to cartilage destruction.

PMID- 15987492
TI  - Screening of an endothelial cDNA library identifies the C-terminal region of
      Nedd5 as a novel autoantigen in systemic lupus erythematosus with psychiatric
      manifestations.
AB  - Anti-endothelial-cell antibodies are associated with psychiatric manifestations
      in systemic lupus erythematosus (SLE). Our primary aim in this study was to seek
      and characterize molecules that behave as endothelial autoantigens in SLE
      patients with psychiatric manifestations. By screening a cDNA library from human
      umbilical artery endothelial cells with serum from an SLE patient with psychosis,
      we identified one positive strongly reactive clone encoding the C-terminal region
      (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family. To evaluate
      anti-Nedd5 serum immunoreactivity, we analyzed by ELISA specific IgG responses in
      17 patients with SLE and psychiatric manifestations (group A), 34 patients with
      SLE without psychiatric manifestations (group B), 20 patients with systemic
      sclerosis, 20 patients with infectious mononucleosis, and 35 healthy subjects.
      IgG specific to Nedd5 C-ter was present in 14 (27%) of the 51 SLE patients. The
      mean optical density value for IgG immunoreactivity to Nedd5 C-ter was
      significantly higher in patients of group A than in those of group B, those with
      infectious mononucleosis, or healthy subjects (0.17 +/- 0.14 vs, respectively,
      0.11 +/- 0.07, P = 0.04; 0.11 +/- 0.06, P = 0.034; and 0.09 +/- 0.045, P = 0.003,
      on Student's t-test). Moreover, IgG immunoreactivity to Nedd5 C-ter was
      significantly higher in patients with systemic sclerosis than in patients of
      group B or healthy subjects (0.18 +/- 0.18 vs, respectively, 0.11 +/- 0.07, P =
      0.046; and 0.09 +/- 0.045, P = 0.003). The percentage of patients with anti-Nedd5
      C-ter serum IgG was higher in group A than in group B (8 (47%) of 17, vs 6 (17%)
      of 34, P = 0.045, on Fisher's exact test). In order to clarify a possible
      mechanism by which Nedd5 might be autoantigenic, we observed that Nedd5 relocated
      from cytoplasm to the plasma membrane of EAhy926 endothelial cells after
      apoptotic stimuli. In conclusion, Nedd5 is a novel autoantigen of potential
      clinical importance that could be successfully used for a more thorough
      investigation of the pathogenesis of psychiatric manifestations in SLE. Although
      anti-Nedd5 autoantibodies are not specific to SLE, they are significantly
      associated with neuropsychiatric SLE and may represent immunological markers of
      psychiatric manifestations in this pathology.

PMID- 15987494
TI  - The role of the complement and the Fc gamma R system in the pathogenesis of
      arthritis.
AB  - Autoantibodies in sera from patients with autoimmune diseases have long been
      known and have become diagnostic tools. Analysis of their functional role again
      became popular with the availability of mice mutant for several genes of the
      complement and Fcgamma receptor (FcgammaR) systems. Evidence from different
      inflammatory models suggests that both systems are interconnected in a
      hierarchical way. The complement system mediators such as complement component 5a
      (C5a) might be crucial in the communication between the complement system and
      FcgammaR-expressing cells. The split complement protein C5a is known to
      inactivate cells by its G-protein-coupled receptor and to be involved in the
      transcriptional regulation of FcgammaRs, thereby contributing to the complex
      regulation of autoimmune disease.

PMID- 15987493
TI  - Catabolic stress induces expression of hypoxia-inducible factor (HIF)-1 alpha in
      articular chondrocytes: involvement of HIF-1 alpha in the pathogenesis of
      osteoarthritis.
AB  - Transcription factor hypoxia-inducible factor (HIF)-1 protein accumulates and
      activates the transcription of genes that are of fundamental importance for
      oxygen homeostasis - including genes involved in energy metabolism, angiogenesis,
      vasomotor control, apoptosis, proliferation, and matrix production - under
      hypoxic conditions. We speculated that HIF-1alpha may have an important role in
      chondrocyte viability as a cell survival factor during the progression of
      osteoarthritis (OA). The expression of HIF-1alpha mRNA in human OA cartilage
      samples was analyzed by real-time PCR. We analyzed whether or not the catabolic
      factors IL-1beta and H2O2 induce the expression of HIF-1alpha in OA chondrocytes
      under normoxic and hypoxic conditions (O2 <6%). We investigated the levels of
      energy generation, cartilage matrix production, and apoptosis induction in HIF
      1alpha-deficient chondrocytes under normoxic and hypoxic conditions. In articular
      cartilages from human OA patients, the expression of HIF-1alpha mRNA was higher
      in the degenerated regions than in the intact regions. Both IL-1beta and H2O2
      accelerated mRNA and protein levels of HIF-1alpha in cultured chondrocytes.
      Inhibitors for phosphatidylinositol 3-kinase and p38 kinase caused a significant
      decrease in catabolic-factor-induced HIF-1alpha expression. HIF-1alpha-deficient
      chondrocytes did not maintain energy generation and cartilage matrix production
      under both normoxic and hypoxic conditions. Also, HIF-1alpha-deficient
      chondrocytes showed an acceleration of catabolic stress-induced apoptosis in
      vitro. Our findings in human OA cartilage show that HIF-1alpha expression in OA
      cartilage is associated with the progression of articular cartilage degeneration.
      Catabolic-stresses, IL-1beta, and oxidative stress induce the expression of HIF
      1alpha in chondrocytes. Our results suggest an important role of stress-induced
      HIF-1alpha in the maintenance of chondrocyte viability in OA articular cartilage.

PMID- 15987495
TI  - Aetiology and pathogenesis of reactive arthritis: role of non-antigen-presenting
      effects of HLA-B27.
AB  - Spondyloarthropathies are inflammatory diseases closely associated with human
      leukocyte antigen (HLA)-B27 by unknown mechanisms. One of these diseases is
      reactive arthritis (ReA), which is typically triggered by Gram-negative bacteria,
      which have lipopolysaccharide as an integral component of their outer membrane.
      Several findings in vivo and in vitro obtained from patients with ReA and from
      different model systems suggest that HLA-B27 modulates the interaction between
      ReA-triggering bacteria and immune cells by a mechanism unrelated to the antigen
      presentation function of HLA-B27. In this review we piece together a jigsaw
      puzzle from the new information obtained from the non-antigen-presenting effects
      of HLA-B27.

PMID- 15987496
TI  - Soluble RAGE: a hot new biomarker for the hot joint?
AB  - The receptor for advanced glycation endproducts (RAGE) interacts with distinct
      ligand families linked to the inflammatory response. Studies in animal models
      suggest that RAGE is upregulated in the inflamed joint and that blockade of the
      receptor, using a ligand decoy soluble form of RAGE (sRAGE), attenuates joint
      inflammation and expression of inflammatory and tissue-destructive mediators. In
      this issue of Arthritis Research & Therapy, Rille Pullerits and colleagues
      reported that plasma levels of sRAGE were reduced in subjects with rheumatoid
      arthritis compared with healthy controls or subjects with non-inflammatory joint
      disease. These findings suggest the possibility that levels of sRAGE might be a
      biomarker of inflammation. Not resolved by these studies, however, is the
      intriguing possibility that endogenously higher levels of sRAGE might be linked
      to a lower incidence of arthritis or to the extent of inflammation. Nevertheless,
      although 'cause or effect' relationships may not be established in this report,
      fascinating insights into RAGE, inflammation and human arthritis emerge from
      these studies.

PMID- 15987497
TI  - Modeling human arthritic diseases in nonhuman primates.
AB  - Models of rheumatoid arthritis (RA) in laboratory animals are important tools for
      research into pathogenic mechanisms and the development of effective, safe
      therapies. Rodent models (rats and mice) have provided important information
      about the pathogenic mechanisms. However, the evolutionary distance between
      rodents and humans hampers the translation of scientific principles into
      effective therapies. The impact of the genetic distance between the species is
      especially seen with treatments based on biological molecules, which are usually
      species-specific. The outbred nature and the closer anatomical, genetic,
      microbiological, physiological, and immunological similarity of nonhuman primates
      to humans may help to bridge the wide gap between inbred rodent strain models and
      the heterogeneous RA patient population. Here we review clinical, immunological
      and pathological aspects of the rhesus monkey model of collagen-induced
      arthritis, which has emerged as a reproducible model of human RA in nonhuman
      primates.

PMID- 15987498
TI  - Histone deacetylases--a new target for suppression of cartilage degradation?
AB  - Increased expression of metalloproteinases is a fundamental aspect of
      arthritispathology and its control is a major therapeutic objective. In cartilage
      cultured in the presence of the cytokines interleukin-1 and oncostatin M,
      chondrocytes produce enhanced levels of metalloproteinases of the ADAMTS (a
      disintegrin and metalloproteinase with thrombospondin motifs) and MMP (matrix
      metalloproteinase) families, resulting in the degradation of aggrecan and
      collagen. The histone deacetylase inhibitors trichostatin A and butyrate were
      shown to drastically reduce expression of these enzymes relatively selectively,
      with concomitant inhibition of breakdown of matrix components. This family of
      enzymes is therefore a promising target for therapeutic intervention.

PMID- 15987499
TI  - Pathogenesis of rheumatoid arthritis: how early is early?
AB  - Studies of cytokine expression in rheumatoid arthritis have provided key insights
      into the pathogenesis of disease and have offered clues for effective therapy.
      Patterns of T-cell products in chronic rheumatoid synovitis suggest that T helper
      type 1 cells contribute to the perpetuation of disease. However, there is no
      guarantee that the mechanisms of late disease are identical to very early
      rheumatoid arthritis. Evaluation of the cytokine profile at the earliest time
      points after onset of symptoms could identify novel targets that prevent
      progression to chronic arthritis.

PMID- 15987500
TI  - ADAMTS proteinases: a multi-domain, multi-functional family with roles in
      extracellular matrix turnover and arthritis.
AB  - Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin
      motifs) family are known to influence development, angiogenesis, coagulation and
      progression of arthritis. As proteinases their substrates include the von
      Willebrand factor precursor and extracellular matrix components such as
      procollagen, hyalectans (hyaluronan-binding proteoglycans including aggrecan),
      decorin, fibromodulin and cartilage oligomeric matrix protein. ADAMTS levels and
      activities are regulated at multiple levels through the control of gene
      expression, mRNA splicing, protein processing and inhibition by TIMP (tissue
      inhibitor of metalloproteinases). A recent screen of human cartilage has shown
      that multiple members of the ADAMTS family may be important in connective tissue
      homeostasis and pathology.

PMID- 15987501
TI  - The TRAF6-NF kappa B signaling pathway in autoimmunity: not just inflammation.

PMID- 15987502
TI  - Fine-needle aspiration of the thyroid: an overview.
AB  - Thyroid nodules (TN) are a common clinical problem. Fine needle aspiration (FNA)
      of the thyroid now is practiced worldwide and proves to be the most economical
      and reliable diagnostic procedure to identify TNs that need surgical excision and
      TNs that can be managed conservatively. The key for the success of thyroid FNA
      consists of an adequate or representative cell sample and the expertise in
      thyroid cytology. The FNA cytologic manifestations of TNs may be classified into
      seven working cytodiagnostic groups consisting of a few heterogenous lesions each
      to facilitate the differential diagnosis. Recent application of diagnostic
      molecular techniques to aspirated thyroid cells proved to be useful in separating
      benign from malignant TNs in several cases of indeterminate lesions.

PMID- 15987503
TI  - Substance P-driven feed-forward inhibitory activity in the mammalian spinal cord.
AB  - In mammals, somatosensory input activates feedback and feed-forward inhibitory
      circuits within the spinal cord dorsal horn to modulate sensory processing and
      thereby affecting sensory perception by the brain. Conventionally, feedback and
      feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn
      is believed to be driven by glutamate, the principle excitatory neurotransmitter
      in primary afferent fibers. Substance P (SP), the prototypic neuropeptide
      released from primary afferent fibers to the dorsal horn, is regarded as a pain
      substance in the mammalian somatosensory system due to its action on nociceptive
      projection neurons. Here we report that endogenous SP drives a novel form of feed
      forward inhibitory activity in the dorsal horn. The SP-driven feed-forward
      inhibitory activity is long-lasting and has a temporal phase distinct from
      glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed
      forward inhibitory activity results in behavioral sensitization. Our findings
      reveal a fundamental role of SP in recruiting inhibitory activity for sensory
      processing, which may have important therapeutic implications in treating
      pathological pain conditions using SP receptors as targets.

PMID- 15987504
TI  - Theme discovery from gene lists for identification and viewing of multiple
      functional groups.
AB  - BACKGROUND: High throughput methods of the genome era produce vast amounts of
      data in the form of gene lists. These lists are large and difficult to interpret
      without advanced computational or bioinformatic tools. Most existing methods
      analyse a gene list as a single entity although it is comprised of multiple gene
      groups associated with separate biological functions. Therefore it is imperative
      to define and visualize gene groups with unique functionality within gene lists.
      RESULTS: In order to analyse the functional heterogeneity within a gene list, we
      have developed a method that clusters genes to groups with homogenous
      functionalities. The method uses Non-negative Matrix Factorization (NMF) to
      create several clustering results with varying numbers of clusters. The obtained
      clustering results are combined into a simple graphical presentation showing the
      functional groups over-represented in the analyzed gene list. We demonstrate its
      performance on two data sets and show results that improve upon existing methods.
      The comparison also shows that our method creates a more simplified view that
      aids in discovery of biological themes within the list and discards less
      informative classes from the results. CONCLUSION: The presented method and
      associated software are useful for the identification and interpretation of
      biological functions associated with gene lists and are especially useful for the
      analysis of large lists.

PMID- 15987506
TI  - The male genital system of the cellar spider Pholcus phalangioides (Fuesslin,
      1775) (Pholcidae, Araneae): development of spermatozoa and seminal secretion.
AB  - BACKGROUND: Most arthropods pass through several molting stages (instars) before
      reaching sexual maturity. In spiders, very little is known about the male genital
      system, its development and seminal secretions. For example, it is unknown
      whether spermatozoa exist prior to-, or only after the final molt. Likewise, it
      is unclear whether sperm are produced throughout male adulthood or only once in a
      lifetime, as is whether seminal secretions contain factors capable of
      manipulating female behavior. In order to shed light on these aspects of the
      reproductive biology of spiders, we investigated the male genital system of the
      common cellar spider Pholcus phalangioides, with special emphasis on its
      development and seminal secretions. RESULTS: Testes already display all stages of
      spermatogenesis in subadult males (about four weeks before the final molt). Their
      vasa deferentia possess proximally a very voluminous lumen containing dense
      seminal fluid and few spermatozoa, whereas the distal part is seemingly devoid of
      contents. Spermatoza of P. phalangioides are typical cleistospermia with
      individual secretion sheaths. In male stages approximately two weeks prior to the
      final molt, the lumina of the testes are wider and filled with a dense secretion.
      The wide, proximal portion of the vasa deferentia is filled with secretion and a
      large number of spermatozoa, and the narrow distal part also contains secretion.
      In adult males, the wide lumina of the testes are packed with spermatozoa and
      secretions. The latter are produced by the somatic cells that bear microvilli and
      contain many vesicles. The lumina of the vasa deferentia are narrow and filled
      with spermatozoa and secretions. We could identify a dense matrix of secretion
      consisting of mucosubstances and at least three types of secretion droplets,
      likely consisting of proteinaceous substances. CONCLUSION: This study reveals
      that spermatogenesis begins weeks before maturity and takes place continuously in
      the long-lived males of P. phalangioides. Possible functions of the various types
      of secretion in the seminal fluid and previously investigated female secretions
      are discussed in the light of sexual selection.

PMID- 15987505
TI  - Dynamic assembly, localization and proteolysis of the Bacillus subtilis SMC
      complex.
AB  - BACKGROUND: SMC proteins are key components of several protein complexes that
      perform vital tasks in different chromosome dynamics. Bacterial SMC forms a
      complex with ScpA and ScpB that is essential for chromosome arrangement and
      segregation. The complex localizes to discrete centres on the nucleoids that
      during most of the time of the cell cycle localize in a bipolar manner. The
      complex binds to DNA and condenses DNA in an as yet unknown manner. RESULTS: We
      show that in vitro, ScpA and ScpB form different complexes with each other, among
      which the level of the putative 2 ScpA/4 ScpB complex showed a pronounced
      decrease in level upon addition of SMC protein. Different mutations of the ATPase
      binding pocket of SMC reduced, but did not abolish interaction of mutant SMC with
      ScpA and ScpB. The loss of SMC ATPase activity led to a loss of function in vivo,
      and abolished proper localization of the SMC complex. The formation of bipolar
      SMC centres was also lost after repression of gyrase activity, and was abnormal
      during inhibition of replication, resulting in single central clusters.
      Resumption of replication quickly re-established bipolar SMC centres, showing
      that proper localization depends on ongoing replication. We also found that the
      SMC protein is subject to induced proteolysis, most strikingly as cells enter
      stationary phase, which is partly achieved by ClpX and LonA proteases. Atomic
      force microscopy revealed the existence of high order rosette-like SMC structures
      in vitro, which might explain the formation of the SMC centres in vivo.
      CONCLUSION: Our data suggest that a ScpA/ScpB sub-complex is directly recruited
      into the SMC complex. This process does not require SMC ATPase activity, which,
      however, appears to facilitate loading of ScpA and ScpB. Thus, the activity of
      SMC could be regulated through binding and release of ScpA and ScpB, which has
      been shown to affect SMC ATPase activity. The proper bipolar localization of the
      SMC complex depends on a variety of physiological aspects: ongoing replication,
      ATPase activity and chromosome supercoiling. Because the cellular concentration
      of SMC protein is also regulated at the posttranscriptional level, the activity
      of SMC is apparently regulated at multiple levels.

PMID- 15987507
TI  - Genetic diversity in populations of asexual and sexual bag worm moths
      (Lepidoptera: Psychidae).
AB  - BACKGROUND: Despite the two-fold cost of sex, most of the higher animals
      reproduce sexually. The advantage of sex has been suggested to be its ability,
      through recombination, to generate greater genetic diversity than asexuality,
      thus enhancing adaptation in a changing environment. We studied the genetic
      diversity and the population structure of three closely related species of bag
      worm moths: two strictly sexual (Dahlica charlottae and Siederia rupicolella) and
      one strictly asexual (D. fennicella). These species compete for the same
      resources and share the same parasitoids. RESULTS: Allelic richness was
      comparable between the sexual species but it was higher than in the asexual
      species. All species showed high heterozygote deficiency and a large variation
      was observed among FIS values across loci and populations. Large genetic
      differentiation was observed between populations confirming the poor dispersal
      ability of these species. The asexual species showed lower genotype diversity
      than the sexual species. Nevertheless, genotype diversity was high in all asexual
      populations. CONCLUSION: The three different species show a similar population
      structure characterised by high genetic differentiation among populations and low
      dispersal. Most of the populations showed high heterozygote deficiency likely due
      to the presence of null alleles at most of the loci and/or to the Wahlund effect.
      Although the parthenogenetic D. fennicella shows reduced genetic diversity
      compared to the sexual species, it still shows surprisingly high genotype
      diversity. While we can not totally rule out the presence of cryptic sex, would
      explain this high genotype diversity, we never observed sex in the
      parthenogenetic D. fennicella, nor was there any other evidence of this.
      Alternatively, a non-clonal parthenogenetic reproduction, such as automictic
      thelytoky, could explain the high genotypic diversity observed in D. fennicella.

PMID- 15987508
TI  - The quality of antimalarials available in Yemen.
AB  - BACKGROUND: Malaria has always been a major public health problem in Yemen.
      Several studies in developing countries have demonstrated ineffective and poor
      quality drugs including antimalarials. Therefore, quality assessment of
      antimalarial drugs is of crucial importance. This study aimed to assess the
      quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine) available in
      Yemen and to determine whether the quality of these products was related to the
      level of the distribution chain at which the samples were collected or related to
      the manufacturers. METHODS: Four samples from each antimalarial product were
      collected from each of the various levels of the distribution chain. One sample
      was kept with the research team. Two were tested at Sana'a and Aden Drug Quality
      Control Laboratories. The fourth was sent to the Centre for Quality Assurance of
      Medicines in Potchefstroom, South Africa, for analysis. Quality indicators
      measured were the content of the active ingredient and dissolution rate (for
      tablets only) in comparison to standard specifications for these products in the
      relevant pharmacopoeia. RESULTS: The results identified several problems of sub
      standard products within the drug distribution chain. They included high and low
      failures in ingredient content for chloroquine tablets and chloroquine syrup.
      There was some dissolution failure for chloroquine tablets, and high
      sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the
      dissolution of the pyrimethamine were found at most of the collection points. No
      clear relationship neither between the quality products and the level of the
      distribution chain, nor between locally manufactured and imported products was
      observed. CONCLUSION: There are sub-standard antimalarial products circulating
      within the drug distribution chains in the country, which will have serious
      implications on the reduced therapeutic effectiveness and on the development of
      drug resistance. This appears to be due to non-compliance with Good Manufacturing
      Practice guidelines by manufacturers in the production of the antimalarials.

PMID- 15987509
TI  - Sentinel node biopsy as an adjunct to limb salvage surgery for epithelioid
      sarcoma of the hand.
AB  - BACKGROUND: Epithelioid sarcomas of the hand are rare, high-grade tumors with a
      propensity for regional lymphatic spread approaching 40%. CASE PRESENTATION: A 54
      year-old male with an epithelioid sarcoma of the palm was treated with
      neoadjuvant radiation, wide excision, and two-stage reconstruction. Sentinel
      lymph node biopsy was used to stage the patient's axilla. Sentinel node biopsy
      results were negative. The patient has remained free of local, regional and
      distant disease for the follow-up time of 16 months. CONCLUSION: The rarity of
      this tumor makes definitive conclusions difficult but SLN biopsy appears to be a
      useful adjunct in the treatment of these sarcomas.

PMID- 15987510
TI  - Conservation of pregnancy-specific glycoprotein (PSG) N domains following
      independent expansions of the gene families in rodents and primates.
AB  - BACKGROUND: Rodent and primate pregnancy-specific glycoprotein (PSG) gene
      families have expanded independently from a common ancestor and are expressed
      virtually exclusively in placental trophoblasts. However, within each species, it
      is unknown whether multiple paralogs have been selected for diversification of
      function, or for increased dosage of monofunctional PSG. We analysed the
      evolution of the mouse PSG sequences, and compared them to rat, human and baboon
      PSGs to attempt to understand the evolution of this complex gene family. RESULTS:
      Phylogenetic tree analyses indicate that the primate N domains and the rodent N1
      domains exhibit a higher degree of conservation than that observed in a
      comparison of the mouse N1 and N2 domains, or mouse N1 and N3 domains. Compared
      to human and baboon PSG N domain exons, mouse and rat PSG N domain exons have
      undergone less sequence homogenisation. The high non-synonymous substitution
      rates observed in the CFG face of the mouse N1 domain, within a context of
      overall conservation, suggests divergence of function of mouse PSGs. The rat PSG
      family appears to have undergone less expansion than the mouse, exhibits lower
      divergence rates and increased sequence homogenisation in the CFG face of the N1
      domain. In contrast to most primate PSG N domains, rodent PSG N1 domains do not
      contain an RGD tri-peptide motif, but do contain RGD-like sequences, which are
      not conserved in rodent N2 and N3 domains. CONCLUSION: Relative conservation of
      primate N domains and rodent N1 domains suggests that, despite independent gene
      family expansions and structural diversification, mouse and human PSGs retain
      conserved functions. Human PSG gene family expansion and homogenisation suggests
      that evolution occurred in a concerted manner that maintains similar functions of
      PSGs, whilst increasing gene dosage of the family as a whole. In the mouse, gene
      family expansion, coupled with local diversification of the CFG face, suggests
      selection both for increased gene dosage and diversification of function. Partial
      conservation of RGD and RGD-like tri-peptides in primate and rodent N and N1
      domains, respectively, supports a role for these motifs in PSG function.

PMID- 15987511
TI  - The evolutionary origins and significance of drug addiction.
AB  - By looking at drug addiction from an evolutionary perspective, we may understand
      its underlying significance and evaluate its three-fold nature: biology,
      psychology, and social influences. In this investigation it is important to delve
      into the co-evolution of mammalian brains and ancient psychotropic plants.
      Gaining an understanding of the implications of ancient psychotropic substance
      use in altering mammalian brains will assist in assessing the causes and effects
      of addiction in a modern-day context. By exploring addiction in this manner, we
      may move towards more effective treatment early prevention, treating the root of
      the issue rather than the symptoms.

PMID- 15987512
TI  - Case report: late perianal mucinous adenocarcinoma after Crohn's disease
      proctectomy: an oncological rarity.
AB  - BACKGROUND: As in ulcerative colitis, there is an increased incidence of
      colorectal carcinoma in Crohn's disease. While carcinoma formation originating
      from ano-rectal fistulas is generally considered as a rare event there are
      different publications reporting on mucinous adenocarcinoma formation in
      association with a neovagina and rectovaginal fistulas. To the best of our
      knowledge this is the first description of a perianal mucinous adenocarcinoma
      arising in a patient after Crohn's disease proctocolectomy. CASE PRESENTATION: We
      report the case of a 50-year old female with a mucinous adenocarcinoma forming in
      the perineum eleven years after proctocolectomy for Crohn's disease. The patient
      was readmitted with perineal pain, leucocytosis and a perineal mass highly
      suspicious of abscess formation in the MRI-Scan. Histological examination
      revealed a mucinous adenocarcinoma. Exenteration including vagina, uterus and
      ovaries together with the coccygeal-bone was performed. CONCLUSION: Mucinous
      adenocarcinoma formation is a rare complication of Crohn's disease and so far
      unreported after proctocolectomy.

PMID- 15987513
TI  - Identifying differential expression in multiple SAGE libraries: an overdispersed
      log-linear model approach.
AB  - BACKGROUND: In testing for differential gene expression involving multiple serial
      analysis of gene expression (SAGE) libraries, it is critical to account for both
      between and within library variation. Several methods have been proposed,
      including the t test, tw test, and an overdispersed logistic regression approach.
      The merits of these tests, however, have not been fully evaluated. Questions
      still remain on whether further improvements can be made. RESULTS: In this
      article, we introduce an overdispersed log-linear model approach to analyzing
      SAGE; we evaluate and compare its performance with three other tests: the two
      sample t test, tw test and another based on overdispersed logistic linear
      regression. Analysis of simulated and real datasets show that both the log-linear
      and logistic overdispersion methods generally perform better than the t and tw
      tests; the log-linear method is further found to have better performance than the
      logistic method, showing equal or higher statistical power over a range of
      parameter values and with different data distributions. CONCLUSION: Overdispersed
      log-linear models provide an attractive and reliable framework for analyzing SAGE
      experiments involving multiple libraries. For convenience, the implementation of
      this method is available through a user-friendly web-interface available at
      http://www.cbcb.duke.edu/sage.

PMID- 15987514
TI  - Wearable feedback systems for rehabilitation.
AB  - In this paper we describe LiveNet, a flexible wearable platform intended for long
      term ambulatory health monitoring with real-time data streaming and context
      classification. Based on the MIT Wearable Computing Group's distributed mobile
      system architecture, LiveNet is a stable, accessible system that combines
      inexpensive, commodity hardware; a flexible sensor/peripheral interconnection
      bus; and a powerful, light-weight distributed sensing, classification, and inter
      process communications software architecture to facilitate the development of
      distributed real-time multi-modal and context-aware applications. LiveNet is able
      to continuously monitor a wide range of physiological signals together with the
      user's activity and context, to develop a personalized, data-rich health profile
      of a user over time. We demonstrate the power and functionality of this platform
      by describing a number of health monitoring applications using the LiveNet system
      in a variety of clinical studies that are underway. Initial evaluations of these
      pilot experiments demonstrate the potential of using the LiveNet system for real
      world applications in rehabilitation medicine.

PMID- 15987515
TI  - Safe storage of methadone in the home--an audit of the effectiveness of safety
      information giving.
AB  - BACKGROUND: Accidental poisoning by methadone occurs, particularly as a result of
      children ingesting a parent's methadone. Health care professionals have a
      responsibility to provide information and guidance to methadone users on safe
      storage of methadone. The objective of the study was to audit the effectiveness
      of information giving on the safety of methadone consumption, dose measurement
      and storage, and the effectiveness of sources of advice available for patients.
      METHODS: The study was undertaken prior to the introduction of a scheme for the
      supervised consumption of methadone, in the setting of an NHS Methadone clinic
      serving a district population of 490,000 in the UK. 185 consecutive patients
      attending a methadone clinic to collect a methadone prescription were the subject
      of an anonymous survey. Issues of safety of methadone consumption, storage and
      safety information provisions were assessed. A telephone survey of the community
      pharmacists dispensing the methadone covered the availability of measuring
      devices and provision of advice on safety was undertaken. RESULTS: Methadone was
      stored in a variety of locations, a cupboard being most frequent. 95 patients
      (60.1%) had children either living in or visiting their home. All stored their
      methadone in a bottle with a child resistant lid; the majority measured doses
      using either the container supplied by the pharmacist or a plastic measure. 126
      patients (78%) confirmed that a pharmacist provided a measuring container on
      their first visit, 24 (15%) were given a measure on every visit to the
      pharmacist. Advice on safe storage was recalled by 30% of the patients, and
      advice on measuring methadone by 28%. Methadone was seen as potentially dangerous
      by 82% of the patients. CONCLUSION: The risks resulting from unsafe storage of
      methadone may be reduced by daily installment prescribing and provision of
      measuring containers on request. Recall of provision of information on safety
      issues is poor and the adoption of a standard policy on provision information
      should be seen as a priority. A re-audit of safety of storage of methadone is
      recommended following the introduction of a standard policy on information
      provision.

PMID- 15987516
TI  - Interaction of silver nanoparticles with HIV-1.
AB  - The interaction of nanoparticles with biomolecules and microorganisms is an
      expanding field of research. Within this field, an area that has been largely
      unexplored is the interaction of metal nanoparticles with viruses. In this work,
      we demonstrate that silver nanoparticles undergo a size-dependent interaction
      with HIV-1, with nanoparticles exclusively in the range of 1-10 nm attached to
      the virus. The regular spatial arrangement of the attached nanoparticles, the
      center-to-center distance between nanoparticles, and the fact that the exposed
      sulfur-bearing residues of the glycoprotein knobs would be attractive sites for
      nanoparticle interaction suggest that silver nanoparticles interact with the HIV
      1 virus via preferential binding to the gp120 glycoprotein knobs. Due to this
      interaction, silver nanoparticles inhibit the virus from binding to host cells,
      as demonstrated in vitro.

PMID- 15987517
TI  - Comparative effects of the herbal constituent parthenolide (Feverfew) on
      lipopolysaccharide-induced inflammatory gene expression in murine spleen and
      liver.
AB  - BACKGROUND: Parthenolide, a major sesquiterpene lactone present in extracts of
      the herb Feverfew, has been investigated for its inhibitory effects on mediators
      of inflammation, including the proinflammatory cytokines. Although parthenolide's
      anti-inflammatory effects have been investigated in vitro, little in vivo data
      are available. Moreover, the molecular mechanisms for these inhibitory effects
      are not fully understood. The objective of this study was to test the hypothesis
      that parthenolide suppresses lipopolysaccharide (LPS)-induced serum (interleukin)
      IL-6, tumor necrosis factor (TNF)-alpha, IL-1beta and cyclooxygenase (COX)-2
      expression in mice as indicated by reduced splenic and liver mRNA levels.
      METHODS: Mice were co-treated i.p. with LPS (1 mg/kg bw) and parthenolide (5
      mg/kg bw) and blood, spleen and liver collected. Serum was analyzed for IL-6, TNF
      alpha and IL-1beta by ELISA. Total RNA was extracted from spleen and liver, and
      real-time RT-PCR was used to determine relative mRNA expression of IL-1beta, IL
      6, TNF-alpha and COX-2. RESULTS: LPS induced increases in serum IL-6 and TNF
      alpha concentrations with only IL-6 being suppressed in parthenolide-treated
      mice. Induction of IL-6 mRNA was reduced, TNF-alpha and COX-2 mRNAs unchanged,
      and IL-1beta mRNA increased in spleens of parthenolide plus LPS co-treated
      animals compared to LPS-only. No significant differences were observed in
      inflammatory gene expression between these two groups in liver samples. Overall,
      mRNA expression of each proinflammatory gene was much higher in spleen when
      compared to liver. CONCLUSION: In summary, only one gene, IL-6, was modestly
      suppressed by parthenolide co-exposure which contrasts with many in vitro studies
      suggesting anti-inflammatory effects of this compound. Also, LPS evoked greater
      effects in spleen than liver on expression of proinflammatory genes. Further
      study of the effects of parthenolide and other herbal constituents on
      inflammatory gene expression using model animal systems as described here are
      critical to evaluating efficacy of such supplements as well as elucidating their
      mechanisms of action.

PMID- 15987518
TI  - Using hierarchical clustering methods to classify motor activities of COPD
      patients from wearable sensor data.
AB  - BACKGROUND: Advances in miniature sensor technology have led to the development
      of wearable systems that allow one to monitor motor activities in the field. A
      variety of classifiers have been proposed in the past, but little has been done
      toward developing systematic approaches to assess the feasibility of
      discriminating the motor tasks of interest and to guide the choice of the
      classifier architecture. METHODS: A technique is introduced to address this
      problem according to a hierarchical framework and its use is demonstrated for the
      application of detecting motor activities in patients with chronic obstructive
      pulmonary disease (COPD) undergoing pulmonary rehabilitation. Accelerometers were
      used to collect data for 10 different classes of activity. Features were
      extracted to capture essential properties of the data set and reduce the
      dimensionality of the problem at hand. Cluster measures were utilized to find
      natural groupings in the data set and then construct a hierarchy of the
      relationships between clusters to guide the process of merging clusters that are
      too similar to distinguish reliably. It provides a means to assess whether the
      benefits of merging for performance of a classifier outweigh the loss of
      resolution incurred through merging. RESULTS: Analysis of the COPD data set
      demonstrated that motor tasks related to ambulation can be reliably discriminated
      from tasks performed in a seated position with the legs in motion or stationary
      using two features derived from one accelerometer. Classifying motor tasks within
      the category of activities related to ambulation requires more advanced
      techniques. While in certain cases all the tasks could be accurately classified,
      in others merging clusters associated with different motor tasks was necessary.
      When merging clusters, it was found that the proposed method could lead to more
      than 12% improvement in classifier accuracy while retaining resolution of 4
      tasks. CONCLUSION: Hierarchical clustering methods are relevant to developing
      classifiers of motor activities from data recorded using wearable systems. They
      allow users to assess feasibility of a classification problem and choose
      architectures that maximize accuracy. By relying on this approach, the clinical
      importance of discriminating motor tasks can be easily taken into consideration
      while designing the classifier.

PMID- 15987520
TI  - Interventions to facilitate health workforce restructure.
AB  - There are recognised shortages in most health professions in Australia. This is
      evidence that previous attempts at health workforce planning have failed. This
      paper argues that one reason for such failure is the lack of appropriate
      structures for health workforce planning. It also suggests that Australia needs
      to move beyond planning for particular professions and that health workforce
      planning needs to be based on identifying skill shortages as much as shortages in
      particular named professionals. The paper proposes specific policy suggestions to
      facilitate workforce flexibility and health workforce planning in Australia.

PMID- 15987519
TI  - Green tea polyphenol extract attenuates lung injury in experimental model of
      carrageenan-induced pleurisy in mice.
AB  - Here we investigate the effects of the green tea extract in an animal model of
      acute inflammation, carrageenan-induced pleurisy. We report here that green tea
      extract (given at 25 mg/kg i.p. bolus 1 h prior to carrageenan), exerts potent
      anti-inflammatory effects in an animal model of acute inflammation in vivo.
      Injection of carrageenan (2%) into the pleural cavity of mice elicited an acute
      inflammatory response characterized by fluid accumulation in the pleural cavity
      that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues
      and increased production of nitrite/nitrate, tumour necrosis factor alpha. All
      parameters of inflammation were attenuated by green tea extract treatment.
      Furthermore, carrageenan induced an up-regulation of the adhesion molecule ICAM
      1, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) formation, as
      determined by immunohistochemical analysis of lung tissues. Staining for the ICAM
      1, nitrotyrosine, and PARS was reduced by green tea extract. Our results clearly
      demonstrate that treatment with green tea extract exerts a protective effect and
      offers a novel therapeutic approach for the management of lung injury.

PMID- 15987521
TI  - A selective cyclic integrin antagonist blocks the integrin receptors alphavbeta3
      and alphavbeta5 and inhibits retinal pigment epithelium cell attachment,
      migration and invasion.
AB  - BACKGROUND: Proliferative vitreoretinopathy (PVR) is a leading cause of blindness
      after failed retinal reattachment surgery. PVR is characterized by the
      proliferation, migration and contraction of retinal pigmented epithelial cells
      (RPE), and these cellular responses are influenced by the expression and function
      of integrin receptors. The effect of a cyclic integrin antagonist containing the
      amino acid sequence Arg-Gly-Asp-D-Phe-Val (RGDfV), specific for the integrin
      receptors alphavbeta3 and alphavbeta5, was investigated on basic fibroblast
      growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), and serum
      induced human RPE proliferation, migration, invasion and attachment to the
      extracellular matrix. Furthermore, the effects of bFGF and PDGF-BB regulated
      expression of integrins alphavbeta3 and alphavbeta5 on RPE cells was examined.
      METHODS: The effect of a cyclic integrin antagonist and a control peptide (0.01
      microg/ml to 300 microg/ml) was investigated on serum or cytokine (bFGF or PDGF
      BB pretreatment) induced human fetal RPE cell proliferation by H3-thymidine
      uptake. The effect of the cyclic integrin antagonist on RPE cell attachment onto
      different extracellular matrices (laminin, collagen IV, fibronectin), RPE cell
      invasion stimulated by PDGF-BB or serum, and migration stimulated by PDGF-BB,
      vascular endothelial growth factor (VEGF) or serum was explored. PDGF-BB and bFGF
      modulation of the integrin receptors alphavbeta3 and alphavbeta5 was evaluated by
      flow cytometry. RESULTS: The integrin antagonist did not inhibit DNA synthesis
      stimulated by serum, bFGF, or PDGF-BB treatment. RPE attachment onto fibronectin
      was inhibited in a concentration range of 1-10 microg/ml (p < 0.05). Attachment
      of the RPE cells onto collagen IV and laminin was inhibited in a range of 3-10
      microg/ml (p < 0.05). Serum and PDGF-BB stimulated migration was inhibited by the
      cyclic integrin antagonist in a concentration range of 1-10 microg/ml (p < 0.05).
      Furthermore, the cyclic integrin antagonist inhibited PDGF-BB stimulated RPE cell
      invasion through fibronectin (3 microg/ml: 66% inhibition, p < 0.001). In each of
      these experiments, the control peptides had no significant effects. PDGF-BB and
      bFGF pretreatment of RPE cells increased the expression of integrin receptors
      alphavbeta3 (bFGF: 1.9 fold, PDGF-BB: 2.3 fold) and alphavbeta5 (bFGF: 2.9 fold,
      PDGF-BB: 1.5 fold). CONCLUSION: A selective inhibition of the integrin receptors
      alphavbeta3 and alphavbeta5 through a cyclic integrin antagonist is able to
      inhibit RPE cell attachment, migration and invasion. Since these steps are of
      importance for the progression of PVR, a cyclic integrin antagonist should be
      further evaluated for the treatment of this disease.

PMID- 15987522
TI  - The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive,
      non-randomized study of cancer-free and oral squamous cell carcinoma subjects.
AB  - BACKGROUND: The purpose of the present investigation was to determine if the
      salivary counts of 40 common oral bacteria in subjects with an oral squamous cell
      carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free)
      controls. METHODS: Unstimulated saliva samples were collected from 229 OSCC-free
      and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria
      using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were
      determined for each species, averaged across subjects in the 2 subject groups,
      and significance of differences between groups determined using the Mann-Whitney
      test and adjusted for multiple comparisons. Diagnostic sensitivity and
      specificity in detection of OSCC by levels of salivary organisms were computed
      and comparisons made separately between a non-matched group of 45 OSCC subjects
      and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age,
      gender and smoking history. RESULTS: Counts of 3 of the 40 species tested,
      Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis,
      were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as
      diagnostic markers the 3 species were found to predict 80% of cancer cases
      (sensitivity) while excluding 83% of controls (specificity) in the non-matched
      group. Diagnostic sensitivity and specificity in the matched group were 80% and
      82% respectively. CONCLUSION: High salivary counts of C. gingivalis, P.
      melaninogenica and S. mitis may be diagnostic indicators of OSCC.

PMID- 15987523
TI  - The impact of a pharmacist-managed dosage form conversion service on
      ciprofloxacin usage at a major Canadian teaching hospital: a pre- and post
      intervention study.
AB  - BACKGROUND: Despite cost containment efforts, parenteral (IV) ciprofloxacin
      appears to be overutilized at Vancouver General Hospital. In November 2003, the
      Pharmacist-managed intravenous to oral (IV-PO) Dosage Form Conversion Service was
      implemented, enabling autonomous pharmacist-initiated dosage form conversion for
      ciprofloxacin. This study evaluates characteristics of ciprofloxacin use prior to
      and following implementation of this conversion service. METHODS: This was a
      single-centre, two-phase (pre/post), unblinded study. Phase I occurred between
      November 12, 2002 and November 11, 2003 (365 days), and Phase II between November
      12, 2003 and March 11, 2004 (120 days). All patients receiving ciprofloxacin IV
      during these periods were reviewed. The primary endpoint was IV:PO ciprofloxacin
      use ratio. Secondary endpoints were total number of ciprofloxacin doses,
      proportion of inappropriate IV ciprofloxacin doses, cost of therapy between
      phases, and estimated cost avoidance with the intervention. RESULTS: Two hundred
      ciprofloxacin IV treatment courses were evaluated (100 per phase). The IV:PO
      ciprofloxacin use ratio was 3.03 (Phase I) vs. 3.48 (Phase II). Total number of
      doses and ratio of IV to total doses across phases were similar (p = 0.2830). IV
      PO ciprofloxacin conversion occurred in 27/100 (27%) of IV courses in Phase I and
      23/100 (23%) in Phase II. Proportion of inappropriate ciprofloxacin IV doses
      decreased between Phases I and II (244/521 (47%) vs. 201/554 (36%) (p = 0.0005),
      respectively). Furthermore, the proportion of pharmacist-preventable
      inappropriate ciprofloxacin IV doses was reduced between Phases I and II (114/244
      (47%) vs. 65/201 (32%) (p = 0.0026). Proportional cost avoidance associated with
      total inappropriate IV use was 7,172 Can dollars/16,517 Can dollars (43%) (in
      Canadian dollars) in Phase I vs. 6,012 Can dollars/17,919 Can dollars (34%) in
      Phase II (p = 0.001). Similarly, proportional cost avoidance associated with
      pharmacist-preventable inappropriate IV doses was reduced from 3,367 Can
      dollars/16,517 Can dollars (20%) in Phase I to 1,975 Can dollars/17,919 Can
      dollars (11%) in Phase II (p = 0.001). CONCLUSION: While overall utilization of
      ciprofloxacin remained unchanged and the proportion of IV to total doses was
      stable during the study period, the proportion of inappropriate IV doses and its
      associated costs appear to have declined subsequent to implementation of a
      Pharmacist-managed IV-PO Dosage Form Conversion Service. Such a program may be a
      beneficial adjunct in facilitating appropriate and cost-effective usage of
      ciprofloxacin.

PMID- 15987525
TI  - Immunologic testing of xeno-derived osteochondral grafts using peripheral blood
      mononuclear cells from healthy human donors.
AB  - BACKGROUND: One means of treating osteoarthritis is with autologous or allogeneic
      osteochondral grafts. The purpose of this study was to evaluate the innate
      immunological response in humans toward xeno-derived osteochondral grafts that
      have been partially or entirely treated by the photooxidation process. METHODS:
      The antigens tested included bovine, porcine, ovine and equine osteochondral
      samples that have been treated in successive steps of photooxidation. ELISPOT
      assays were used to evaluate the production of IL-1, IL-4, IL-6, IL-10, IL-12 and
      TNF-alpha by human monocytes in response to the antigens. RESULTS: Results
      indicated vigorous production of IL-1, IL-6, IL-10 and TNF-alpha in response to
      untreated bovine, porcine and equine specimens. This indicates that these samples
      are perceived as foreign, or stimulatory, by the human monocytes. There was no
      induction of IL-4 or IL-12, which is required for Th2 and Th1 immunity,
      respectively. In contrast, the processed bovine, porcine and equine samples did
      not induce significant activation of cells of the innate immune system. This
      occurred after the first step in processing (after cleaning in increasing
      strengths of ethanol). This suggests that the processing steps dramatically, if
      not completely, negated the immunostimulatory properties of the test sample. The
      results for the ovine samples indicate a reverse response. CONCLUSION: The
      findings of the study suggest that photooxidized bovine, porcine or equine
      samples have the potential to be used as an osteochondral graft. Although the
      first step in processing reduced the immunological response, photooxidation is
      still necessary to retain the structure and mechanical integrity of the
      cartilage, which would allow for immediate joint resurfacing.

PMID- 15987524
TI  - Qualitatively and quantitatively similar effects of active and passive maternal
      tobacco smoke exposure on in utero mutagenesis at the HPRT locus.
AB  - BACKGROUND: Induced mutagenesis in utero is likely to have life-long
      repercussions for the exposed fetus, affecting survival, birth weight and
      susceptibility to both childhood and adult-onset diseases, such as cancer. In the
      general population, such exposures are likely to be a consequence of the
      lifestyle choices of the parents, with exposure to tobacco smoke one of the most
      pervasive and easily documented. Previous studies attempting to establish a
      direct link between active smoking and levels of somatic mutation have largely
      discounted the effects of passive or secondary exposure, and have produced
      contradictory results. METHODS: Data from three studies of possible smoking
      effects on in utero mutagenesis at the HPRT locus were compiled and reanalyzed,
      alone and in combination. Where possible, passive exposure to environmental
      tobacco smoke was considered as a separate category of exposure, rather than
      being included in the non-smoking controls. Molecular spectra from these studies
      were reanalyzed after adjustment for reported mutation frequencies from the
      individual studies and the entire data set. RESULTS: A series of related studies
      on mutation at the X-linked HPRT locus in human newborn cord blood samples has
      led to the novel conclusion that only passive maternal exposure to tobacco
      mutagens has a significant effect on the developing baby. We performed a pooled
      analysis of the complete data from these studies, at the levels of both induced
      mutation frequency and the resulting mutational spectrum. CONCLUSION: Our
      analysis reveals a more commonsensical, yet no less cautionary result: both
      active maternal smoking and secondary maternal exposure produce quantitatively
      and qualitatively indistinguishable increases in fetal HPRT mutation. Further, it
      appears that this effect is not perceptibly ameliorated if the mother adjusts her
      behavior (i.e. stops smoking) when pregnancy is confirmed, although this
      conclusion may also be affected by continued passive exposure.

PMID- 15987527
TI  - Review of Doody's Core Titles in the Health Sciences 2004 (DCT 2004).

PMID- 15987526
TI  - Electronic learning can facilitate student performance in undergraduate surgical
      education: a prospective observational study.
AB  - BACKGROUND: Our institution recently introduced a novel internet accessible
      computer aided learning (iCAL) programme to complement existing surgical
      undergraduate teaching methods. On graduation of the first full cycle of
      undergraduate students to whom this resource was available we assessed the
      utility of this new teaching facility. METHOD: The computer programme
      prospectively records usage of the system on an individual user basis. We
      evaluated the utilisation of the web-based programme and its impact on class
      ranking changes from an entry-test evaluation to an exit examination in surgery.
      RESULTS: 74.4% of students were able to access iCAL from off-campus internet
      access. The majority of iCAL usage (64.6%) took place during working hours (08:00
      18:00) with little usage on the weekend (21.1%). Working hours usage was
      positively associated with improvement in class rank (P = 0.025, n = 148) but out
      of hours usage was not (P = 0.306). Usage during weekdays was associated with
      improved rank (P = 0.04), whereas weekend usage was not (P = 0.504). There were
      no significant differences in usage between genders (P = 0.3). Usage of the iCAL
      system was positively correlated with improvement in class rank from the entry to
      the exit examination (P = 0.046). Students with lower ranks on entry examination,
      were found to use the computer system more frequently (P = 0.01). CONCLUSION:
      Electronic learning complements traditional teaching methods in undergraduate
      surgical teaching. Its is more frequently used by students achieving lower class
      ranking with traditional teaching methods, and this usage is associated with
      improvements in class ranking.

PMID- 15987528
TI  - Prospective assessment of Y-chromosome microdeletions and reproductive outcomes
      among infertile couples of Japanese and African origin.
AB  - BACKGROUND: To compare the frequency of Y-chromosome microdeletions in Japanese
      and African azoospermic and oligozoospermic men and describe embryo
      characteristics and reproductive outcome following in vitro fertilization (IVF)
      with intracytoplasmic sperm injection (ICSI). METHODS: Our study was performed
      prospectively at two centers, a private IVF clinic and a university hospital.
      Japanese and African (Tanzanian) men with nonobstructive azoospermia (NOA) and
      oligozoospermia (concentration < 5 x 10(6) /ml) were evaluated for Y-chromosome
      microdeletions (n = 162). Of the 47 men with NOA, 26 were Japanese and 21 were
      Africans. Of the 115 men with oligozoospermia, 87 were Japanese and 28 were
      Africans. Reproductive outcomes of patients with Y-chromosome microdeletions were
      then compared with those of 19 IVF+ICSI cycles performed on couples with Y
      chromosome intact males/tubal factor infertility which served as a control group.
      RESULTS: Seven azoospermic and oligozoospermic patients had Y-chromosome
      deletions; the total number of deletions in the AZFc region was five. There was
      only one deletion in the AZFa region and one complete deletion involving all
      three regions (AZFa, b, and c) within AZF. In our study population, microdeletion
      frequency among Japanese men was 6.2% (95% CI, 4.25%-14.45%), whereas no
      deletions were identified in the African group (95% CI, 0.0%-7.27%). The
      difference between the two groups was not statistically significant, however.
      Embryos derived from ICSI utilizing sperm with Y-chromosome microdeletion showed
      reduced rates of fertilization, blastocyst development, implantation, and
      pregnancy compared to the Y-chromosome intact group, although these observed
      differences were not statistically significant. CONCLUSION: The observed
      frequency of Y-chromosome microdeletion was 6.2% among Japanese azoospermic and
      oligozoospermic males; no microdeletions were identified among our African study
      patients. In this population of couples undergoing IVF+ICSI, there was no
      statistically significant difference in embryo characteristics or pregnancy
      outcome between patients with Y-chromosome microdeletion and those with an intact
      Y-chromosome.

PMID- 15987529
TI  - Signal transduction pathway profiling of individual tumor samples.
AB  - BACKGROUND: Signal transduction pathways convey information from the outside of
      the cell to transcription factors, which in turn regulate gene expression. Our
      objective is to analyze tumor gene expression data from microarrays in the
      context of such pathways. RESULTS: We use pathways compiled from the
      TRANSPATH/TRANSFAC databases and the literature, and three publicly available
      cancer microarray data sets. Variation in pathway activity, across the samples,
      is gauged by the degree of correlation between downstream targets of a pathway.
      Two correlation scores are applied; one considers all pairs of downstream
      targets, and the other considers only pairs without common transcription factors.
      Several pathways are found to be differentially active in the data sets using
      these scores. Moreover, we devise a score for pathway activity in individual
      samples, based on the average expression value of the downstream targets.
      Statistical significance is assigned to the scores using permutation of genes as
      null model. Hence, for individual samples, the status of a pathway is given as a
      sign, + or -, and a p-value. This approach defines a projection of high
      dimensional gene expression data onto low-dimensional pathway activity scores.
      For each dataset and many pathways we find a much larger number of significant
      samples than expected by chance. Finally, we find that several sample-wise
      pathway activities are significantly associated with clinical classifications of
      the samples. CONCLUSION: This study shows that it is feasible to infer signal
      transduction pathway activity, in individual samples, from gene expression data.
      Furthermore, these pathway activities are biologically relevant in the three
      cancer data sets.

PMID- 15987530
TI  - Species-specific analysis of protein sequence motifs using mutual information.
AB  - BACKGROUND: Protein sequence motifs are by definition short fragments of
      conserved amino acids, often associated with a specific function. Accordingly
      protein sequence profiles derived from multiple sequence alignments provide an
      alternative description of functional motifs characterizing families of related
      sequences. Such profiles conveniently reflect functional necessities by pointing
      out proximity at conserved sequence positions as well as depicting distances at
      variable positions. Discovering significant conservation characteristics within
      the variable positions of profiles mirrors group-specific and, in particular,
      evolutionary features of the underlying sequences. RESULTS: We describe the tool
      PROfile analysis based on Mutual Information (PROMI) that enables comparative
      analysis of user-classified protein sequences. PROMI is implemented as a web
      service using Perl and R as well as other publicly available packages and tools
      on the server-side. On the client-side platform-independence is achieved by
      generally applied internet delivery standards. As one possible application
      analysis of the zinc finger C2H2-type protein domain is introduced to illustrate
      the functionality of the tool. CONCLUSION: The web service PROMI should assist
      researchers to detect evolutionary correlations in protein profiles of defined
      biological sequences. It is available at http://promi.mpimp-golm.mpg.de where
      additional documentation can be found.

PMID- 15987531
TI  - Shape based assignment tests suggest transgressive phenotypes in natural sculpin
      hybrids (Teleostei, Scorpaeniformes, Cottidae).
AB  - BACKGROUND: Hybridization receives attention because of the potential role that
      it may play in generating evolutionary novelty. An explanation for the emergence
      of novel phenotypes is given by transgressive segregation, which, if frequent,
      would imply an important evolutionary role for hybridization. This process is
      still rarely studied in natural populations as samples of recent hybrids and
      their parental populations are needed. Further, the detection of transgressive
      segregation requires phenotypes that can be easily quantified and analysed. We
      analyse variability in body shape of divergent populations of European sculpins
      (Cottus gobio complex) as well as natural hybrids among them. RESULTS: A distance
      based method is developed to assign unknown specimens to known groups based on
      morphometric data. Apparently, body shape represents a highly informative set of
      characters that parallels the discriminatory power of microsatellite markers in
      our study system. Populations of sculpins are distinct and "unknown" specimens
      can be correctly assigned to their source population based on body shape. Recent
      hybrids are intermediate along the axes separating their parental groups but
      display additional differentiation that is unique and coupled with the hybrid
      genetic background. CONCLUSION: There is a specific hybrid shape component in
      natural sculpin hybrids that can be best explained by transgressive segregation.
      This inference of how hybrids differ from their ancestors provides basic
      information for future evolutionary studies. Furthermore, our approach may serve
      to assign candidate specimens to their source populations based on morphometric
      data and help in the interpretation of population differentiation.

PMID- 15987532
TI  - Silencing the epidermal growth factor receptor gene with RNAi may be developed as
      a potential therapy for non small cell lung cancer.
AB  - Lung cancer has emerged as a leading cause of cancer death in the world. Non
      small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. Current
      therapies are ineffective, thus new approaches are needed to improve the
      therapeutic ratio. Double stranded RNA (dsRNA)-mediated RNA interference (RNAi)
      has shown promise in gene silencing, the potential of which in developing new
      methods for the therapy of NSCLC needs to be tested. We report here RNAi induced
      effective silencing of the epidermal growth factor receptor (EGFR) gene, which is
      over expressed in NSCLC. NSCLC cell lines A549 and SPC-A1 were transfected with
      sequence- specific dsRNA as well as various controls. Immune fluorescent labeling
      and flow cytometry were used to monitor the reduction in the production of EGFR
      protein. Quantitative reverse-transcriptase PCR was used to detect the level of
      EGFR mRNA. Cell count, colony assay, scratch assay, MTT assay in vitro and tumor
      growth assay in athymic nude mice in vivo were used to assess the functional
      effects of EGFR silencing on tumor cell growth and proliferation. Our data showed
      transfection of NSCLC cells with dsRNA resulted in sequence specific silencing of
      EGFR with 71.31% and 71.78 % decreases in EGFR protein production and 37.04% and
      54.92% in mRNA transcription in A549 and SPC-A1 cells respectively. The decrease
      in EGFR protein production caused significant growth inhibition, i.e.: reducing
      the total cell numbers by 85.0% and 78.3%, and colony forming numbers by 63.3%
      and 66.8%. These effects greatly retarded the migration of NSCLC cells by more
      than 80% both at 24 h and at 48 h, and enhanced chemo-sensitivity to cisplatin by
      four-fold in A549 cells and seven-fold in SPC-A1. Furthermore, dsRNA specific for
      EGFR inhibited tumor growth in vivo both in size by 75.06% and in weight by
      73.08%. Our data demonstrate a new therapeutic effect of sequence specific
      suppression of EGFR gene expression by RNAi, enabling inhibition of tumor
      proliferation and growth. However, in vivo use of dsRNA for gene transfer to
      tumor cells would be limited because dsRNA would be quickly degraded once
      delivered in vivo. We thus tested a new bovine lentiviral vector and showed
      lentivector-mediated RNAi effects were efficient and specific. Combining RNAi
      with this gene delivery system may enable us to develop RNAi for silencing EGFR
      into an effective therapy for NSCLC.

PMID- 15987533
TI  - Development of a Multiple-Locus Variable Number of Tandem Repeat Analysis (MLVA)
      for Leptospira interrogans and its application to Leptospira interrogans serovar
      Australis isolates from Far North Queensland, Australia.
AB  - BACKGROUND: Leptospirosis is a zoonotic disease caused by the genus, Leptospira.
      Leptospira interrogans is the most common genomospecies implicated in the
      disease. Epidemiological investigations are needed to distinguish outbreak
      situations or to trace reservoirs of the organisms. Current methodologies used
      for typing Leptospira have significant drawbacks. The development of an easy to
      perform yet high resolution method is needed for this organism. METHODS: In this
      study we have searched the available genomic sequence of L. interrogans serovar
      Copenhageni strain Fiocruz L1-130 for the presence of tandem repeats. These
      repeats were evaluated against reference strains for diversity. Six loci were
      selected to create a Multiple Locus Variable Number of Tandem Repeats (VNTR)
      Analysis (MLVA) to explore the genetic diversity within L. interrogans serovar
      Australis clinical isolates from Far North Queensland. RESULTS: The 39 reference
      strains used for the development of the method displayed 39 distinct patterns.
      Diversity Indexes for the loci varied between 0.80 and 0.93 and the number of
      repeat units at each locus varied between less than one to 52 repeats. When the
      MLVA was applied to serovar Australis isolates three large clusters were
      distinguishable, each comprising various hosts including Rattus species, human
      and canines. CONCLUSION: The MLVA described in this report, was easy to perform,
      analyse and was reproducible. The loci selected had high diversity allowing
      discrimination between serovars and also between strains within a serovar. This
      method provides a starting point on which improvements to the method and
      comparisons to other techniques can be made.

PMID- 15987534
TI  - Trends in hospitalization and mortality for subarachnoid hemorrhage and
      unruptured aneurysms in the United States.
AB  - OBJECTIVE: During the past decade, endovascular obliteration of intracranial
      aneurysms and new treatments for vasospasm and cerebral ischemia have been
      introduced. To analyze the effectiveness of these new strategies, we evaluated
      changes in morbidity and mortality rates in patients at least 18 years of age who
      were hospitalized for ruptured and unruptured intracranial aneurysms during the
      past 16 years. METHODS: National estimates of hospitalization for subarachnoid
      hemorrhage (SAH) and unruptured intracranial aneurysms and associated in-hospital
      outcomes and mortality were obtained from National Hospital Discharge Survey
      data. All the variables pertaining to hospitalization were compared for three
      distinct time periods: 1986-1990, 1991-1995, and 1996-2001. RESULTS: There were
      94,692, 104,746, and 133,269 admissions for SAH during the periods 1986-1990,
      1991-1995, and 1996-2001, respectively. Mortality rates for hospitalizations
      related to SAH demonstrated no significant change in mortality during the periods
      1986-1990, 1991-1995, and 1996-2001 (27.6%, 24.6%, and 26.3%, respectively.
      Procedures performed for SAH from 1996 to 2001 included surgical clipping (28%),
      endovascular/wrapping (2%), and no procedure (70%). The number of admissions for
      unruptured intracranial aneurysms was 23,481 from 1986 to 1990, 28,017 from 1991
      to 1995, and 51,904 from 1996 to 2001. There was an overall trend (P = 0.07)
      toward reduced in-hospital mortality during the three periods: 5.9%, 6.3%, and
      1.4% for 1986-1990, 1991-1995, and 1996-2001, respectively. CONCLUSION: The
      mortality rate for unruptured intracranial aneurysms demonstrates a significant
      trend of reduction during the past 16 years. The mortality rate for SAH
      demonstrates limited change during the same period; it is presumed that this is
      attributable to the multitude of factors that influence outcome.

PMID- 15987535
TI  - Effect of the neurosurgeon's surgical experience on outcomes from intraoperative
      aneurysmal rupture.
AB  - OBJECTIVE: The neurosurgeon's surgical experience is one of the most important
      and least studied factors affecting a patient's outcome after an intraoperative
      rupture of an aneurysm. Therefore, this analysis was undertaken to evaluate the
      effect of the neurosurgeon's experience on the management of this catastrophe in
      a consecutive series of patients treated microsurgically. METHODS: The
      neurosurgeon's surgical experience was analyzed in terms of annual aneurysm case
      volume and duration. Management of intraoperative aneurysmal rupture was analyzed
      in terms of timing of rupture, duration of temporary clipping, and neurological
      outcomes using the Glasgow Outcome Scale. During a 7-year period in which 1038
      aneurysms were treated microsurgically in 838 patients, 68 (6.6%) ruptured
      intraoperatively. RESULTS: The neurosurgeon's annual aneurysm case volume
      increased by 35% over this period, and mean case duration decreased by 31%. The
      annual frequency of intraoperative ruptures fluctuated, with most (88%) occurring
      with previously ruptured aneurysms in patients with subarachnoid hemorrhage. With
      increasing surgical experience, the number of ruptures during predissection and
      clip application, the mean duration of temporary clipping, and the surgical
      mortality rate all declined, whereas the number of patients experiencing a good
      outcome (Glasgow Outcome Scale score of 5 or 4) increased. CONCLUSION:
      Intraoperative rupture is an unavoidable danger in aneurysm surgery that does not
      diminish with increasing surgical experience of the neurosurgeon performing the
      operation. However, experience did improve the neurosurgeon's response to
      aneurysm rupture and the patients' outcomes. Mental anticipation and technical
      repetition over time transform into efficiency, confidence, and insight in the
      management of this distressing intraoperative event.

PMID- 15987536
TI  - D-dimer predicts outcome after aneurysmal subarachnoid hemorrhage: no effect of
      thromboprophylaxis on coagulation activity.
AB  - OBJECTIVE: Approximately one-third of all patients with acute nontraumatic
      subarachnoid hemorrhage (SAH) experience complications owing to delayed ischemic
      deficit. We reported recently that enoxaparin 40 mg once daily for 10 days seems
      safe and demonstrates thromboprophylactic efficacy, but it failed to improve
      outcome in a randomized SAH trial. In the present study, we assessed hemostatic
      variables associated with clinical status and outcome of SAH. We also monitored
      the effect of enoxaparin on activation of coagulation and fibrinolysis after
      closure of the ruptured aneurysm. METHODS: Blood samples to measure activation of
      coagulation and fibrinolysis were collected from 42 patients participating in the
      enoxaparin trial for acute aneurysmal SAH at four time points: 1) at hospital
      admission; 2) 12 to 24 hours after aneurysm surgery but before initiation of
      enoxaparin therapy; 3) 3 hours after the first dose; and 4) at the conclusion of
      treatment. RESULTS: At admission, several variables of coagulation and
      fibrinolysis were elevated and correlated well with clinical status.
      Specifically, D-dimer levels at all four time points correlated with patients'
      long-term outcomes. A single dose of enoxaparin suppressed early coagulation
      activity, but thrombin generation was not inhibited during thromboprophylaxis.
      However, PAI-1 activity was suppressed. CONCLUSION: D-dimer offers a useful
      laboratory tool for assessing early and late clinical severity of SAH. A
      thromboprophylactic dose of enoxaparin inhibited PAI-1 activity but failed to
      down-regulate coagulation activity and D-dimer. These findings are compatible
      with the lack of efficacy of enoxaparin in reducing ischemic deficit after SAH.

PMID- 15987537
TI  - Survival of cardiac arrest after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Survival of cardiac arrest (CA) after aneurysmal subarachnoid
      hemorrhage (SAH) is poorly characterized. We analyzed the clinical course and
      outcome of patients who survived resuscitation for CA after aneurysmal SAH.
      METHODS: Medical records of all patients with acute SAH treated at Mayo Clinic
      between 1990 and 1997 were reviewed. Three hundred five consecutive patients with
      angiographically proven aneurysmal SAH presenting within 7 days of ictus were
      analyzed. CA was defined as a pulseless state, documented by medical personnel,
      for which resuscitation was performed. Outcome was measured with the Glasgow
      Outcome Scale score at longest follow-up (mean, 16 mo). RESULTS: Data from 11
      patients (3.6%) who had 14 episodes of CA were analyzed. Six patients had CA
      before reaching the hospital and were successfully resuscitated. Nine of 14 CA
      episodes occurred at hemorrhage or rehemorrhage. No patient with in-hospital CA
      failed to be resuscitated. Overall mortality in patients who had CA (46%) was
      higher than that of patients without CA (15%; P = 0.019). Outcome for all
      patients who had CA (mean Glasgow Outcome Scale score, 2.5) was worse than for
      patients without CA (mean Glasgow Outcome Scale score, 3.9; P = 0.005). However,
      half of the survivors of CA after SAH were living independently with limited
      deficit at longest follow-up. CONCLUSION: Most cases of CA occur at the time of
      initial or recurrent SAH. Resuscitation for in-hospital CA is likely to be
      successful. Although CA after aneurysmal SAH is associated with significantly
      higher mortality, the outcome of survivors of CA is not worse than that for other
      patients after aneurysmal SAH.

PMID- 15987538
TI  - Comparison of conventional region of interest and statistical mapping method in
      brain single-photon emission computed tomography for prediction of hyperperfusion
      after carotid endarterectomy.
AB  - OBJECTIVE: Hyperperfusion after carotid endarterectomy (CEA) has been proposed as
      the main mechanism of intracerebral hemorrhage, which is a disastrous
      complication. The aim of this study was to compare the predictive value of
      cerebral blood flow (CBF) abnormalities for hyperperfusion after CEA with the
      conventional region of interest (ROI) analysis and statistical brain mapping
      analysis. METHODS: For 46 patients with unilateral carotid stenosis of 70% or
      more, CBF and cerebral vasoreactivity were investigated with resting and
      acetazolamide-challenge single-photon emission computed tomography before CEA and
      1 day after CEA. Three-dimensional stereotactic surface projection (3-D-SSP)
      analysis of CBF changes was performed by automatic quantification with a
      predefined template. RESULTS: Logistic regression analysis demonstrated CBF
      reduction (z-score) to be the only significant variable for postoperative
      hyperperfusion on 3-D-SSP with thalamic normalization but no significant variable
      with the ROI method. Receiver operating characteristic (ROC) analysis
      demonstrated significant improvement in the predictive value of CBF reduction (z
      score) on 3-D-SSP (area under the ROC curve = 0.93) in comparison with the ROI
      method (area under the ROC curve = 0.78) (P = 0.049). According to the optimal
      cutoff values provided by ROC analysis, patients were categorized into two
      groups: Type I (CBF decrease < 20%, n = 23) and Type II (CBF decrease > or = 20%,
      n = 23) on ROI analysis and Type A (z-score < or = 2, n = 40) and Type B (z-score
      > 2, n = 6) on 3-D-SSP. There was a significant difference in incidence of
      hyperperfusion between Type A (1 of 40) and Type B (5 of 6) on 3-D-SSP (P =
      0.00003) but not between Type I (1 of 23) and Type II (5 of 23) on ROI analysis.
      Cerebral vasoreactivity did not show significant value in the prediction of
      hyperperfusion with either the ROI or the 3-D-SSP method. CONCLUSION: Objective
      assessment of CBF status, especially baseline CBF reduction (z-score), with
      automatic quantification by 3-D-SSP with normalization had a higher diagnostic
      value than conventional ROI analysis to identify patients at risk for
      hyperperfusion after CEA.

PMID- 15987539
TI  - Long-term results after fractionated radiation therapy for large brain
      arteriovenous malformations.
AB  - OBJECTIVE: To study the results after fractionated radiotherapy of large
      arteriovenous malformations (AVMs). METHODS: Twenty-eight patients harboring
      large AVMs were treated between 1980 and 1985 with fractionated radiotherapy with
      up to 3.5 Gy per fraction twice a week to a total dose of 41 to 50 Gy. All but 5
      patients were examined with an angiogram at least 4 years after the treatment.
      RESULTS: Two AVMs (8%) were obliterated after the treatment. Eight patients died:
      five as a result of hemorrhages, two of unknown causes, and one as a result of
      lung carcinoma. Five patients deteriorated slightly, three moderately, and four
      severely after the treatment. The longer the observation time, the higher the
      incidence of neurological deterioration. The AVMs were significantly larger in
      the four patients who developed a severe deficit after the treatment. The annual
      hemorrhage rate was 6% after the treatment, suggesting that radiation did not
      protect from hemorrhage unless the AVM was occluded. AVMs with a pretreatment
      rupture had a annual hemorrhage rate of 12%, compared with 1% in the unruptured
      cases. CONCLUSION: The obliteration rate after fractionated radiotherapy with a
      dose per fraction of 2 to 4 Gy to a total dose of up to 50 Gy was low. The
      clinical outcome suggests that the radiation treatment may have caused
      significant side effects. Although the risk for hemorrhage in previously ruptured
      large AVMs is high, the use of fractionated radiotherapy using low doses per
      fraction cannot be recommended.

PMID- 15987540
TI  - Sensory and motor interhemispheric integration after section of different
      portions of the anterior corpus callosum in nonepileptic patients.
AB  - OBJECTIVE: We evaluated somatosensory and motor interhemispheric integration in
      four patients who underwent transection of different portions of the anterior
      corpus callosum (CC) for removal of an intraventricular cyst. The study goal was
      to relate their performances to the topographical organization of the CC.
      METHODS: Experimental tasks included bimanual coordination, tactile cross
      localization, and intermanual and interfield comparisons of somesthetic
      information. Response accuracy and response times were measured. In addition,
      interhemispheric transmission times were obtained in the somesthetic modality.
      RESULTS: Section of the middle portion of the genu caused a deficit in motor
      coordination, which was absent in patients with more posteriorly located lesions,
      whereas section of more rostral portions of the genu seemed to interfere with
      motor planning. The most posterior section in our sample, including the anterior
      portion of the body of the corpus, abolished interhemispheric transfer of simple
      somesthetic information (perception of touch) but not tactile discrimination
      (intermanual comparisons of shapes). We speculate that more complex somesthetic
      information is transferred through the caudal region of the body of the CC, which
      was spared in all patients. Thus, it seems that section of different portions of
      the anterior CC (genu and anterior body) produces specific deficits in
      interhemispheric integration in the motor and somesthetic modalities. These
      deficits are consistent with the anteroposterior topography of anterior callosal
      fibers. CONCLUSION: The specific disconnections deficits observed in this study
      may provide the surgeon with information regarding the consequences of anterior
      callosotomy and allow for remedial measures to be implemented if required.

PMID- 15987541
TI  - Stereotactic radiotherapy for vestibular schwannomas: favorable outcome with
      minimal toxicity.
AB  - OBJECTIVE: To determine the outcome and toxicity in patients with vestibular
      schwannomas treated with conventionally fractionated stereotactic radiotherapy
      (SRT) and to identify prognostic factors that are predictive of outcome. METHODS:
      Between 1992 and 2001, 70 patients with vestibular schwannomas were treated with
      linear accelerator-based SRT in our institutions. Eleven patients had
      neurofibromatosis Type II (NF2). The median age was 53 years (range, 17-82 yrs).
      The median tumor volume was 2.4 cm3 (range, 0.05-21.1 cm3). The indications for
      SRT were distributed as follows: 47% newly diagnosed, 31% progressive tumors
      after watchful waiting, 3% adjuvant postoperative radiation, and 19% recurrent
      tumors after surgical resection. The median dose was 54 Gy in 1.8 Gy per
      fraction, prescribed to 95% of the isodose line. Relocatable stereotactic frames
      were used for daily treatments. The median follow-up was 45.3 months. RESULTS:
      Tumor recurrence was defined as progressive enlargement of tumor on follow-up
      magnetic resonance imaging studies. One patient had a tumor recurrence at 38
      months after SRT. The actuarial tumor control rates were 100 and 98% at 3 and 5
      years, respectively. Three patients with a median tumor volume of 16.2 cm3
      required surgical resection for persistent or increasing symptoms at a median of
      37 months. The actuarial freedom from resection rates were 98 and 92% at 3 and 5
      years, respectively. In multivariate analysis, tumor volume at time of treatment
      was predictive for neurosurgical intervention (surgical resection or shunt
      placement) after SRT (P = 0.001). The 3- and 5-year actuarial rates of freedom
      from any neurosurgical intervention were 100 and 97% for patients with tumor
      volume less than 8 cm3 and 74 and 47% respectively for patients with tumor of at
      least 8 cm3 (P < 0.0001). The 3-year actuarial rates of facial and trigeminal
      nerve preservation were 99 and 96%, respectively. Surgery before SRT was
      predictive of posttreatment trigeminal neuropathy. The 3-year actuarial rates of
      freedom from trigeminal neuropathy were 86 and 98% for patients with and without
      previous resection, respectively (P = 0.04). There was no difference in tumor
      control and cranial nerve function preservation rates seen in NF2 patients
      compared with non-NF2 patients. No second primary cancer or malignant
      transformation was observed. CONCLUSION: SRT in the conventionally fractionated
      approach results in a very favorable outcome with minimal toxicity, with results
      comparable to those of the best of the radiosurgery series. Patients with large
      tumors are more likely to undergo neurosurgical interventions after SRT. Patients
      who have undergone previous surgery are at increased risk of developing
      trigeminal neuropathy.

PMID- 15987542
TI  - Risk of hemorrhage in hemangioblastomas of the central nervous system.
AB  - OBJECTIVE: Hemangioblastomas are benign vascular tumors of the central nervous
      system. Several cases of spontaneous hemorrhage within these tumors have been
      reported. However, the risk of hemorrhage in these tumors remains unknown.
      METHODS: To clarify the incidence of hemorrhage in hemangioblastomas, we reviewed
      our large clinical database of 277 patients with central nervous system
      hemangioblastomas for the incidence of spontaneous or perioperative hemorrhage.
      Clinical characteristics such as tumor size, tumor location, von Hippel-Lindau
      disease status, and clinical symptoms before hemorrhage were correlated with
      hemorrhage risk. Furthermore, we reviewed the literature for cases of spontaneous
      hemorrhage from hemangioblastoma. RESULTS: Among all patients in our series, we
      observed seven cases of spontaneous hemorrhage from a hemangioblastoma within the
      summarized follow-up time. Thus, we calculate a spontaneous hemorrhage
      probability of 0.0024 per person per year. The average diameter of tumors that
      bled was 3 cm in our series and 2.3 cm in the literature review, whereas the
      average diameter of hemangioblastomas in major series ranges from 0.8 to 1.1 cm.
      Furthermore, we have observed severe postoperative hemorrhage in two
      extraordinarily large solid hemangioblastomas (4 and 5 cm). CONCLUSION: The
      overall incidence of hemorrhage in patients with hemangioblastoma is low. An
      important indicator for the probability of hemorrhage is tumor size, as
      spontaneous or postoperative hemorrhage occurred exclusively in extraordinarily
      large tumors. Hemangioblastomas smaller than 1.5 cm (the vast majority of these
      tumors) harbor virtually no risk of spontaneous hemorrhage.

PMID- 15987543
TI  - Facial and cochlear nerve function after surgery of cerebellopontine angle
      meningiomas.
AB  - OBJECTIVE: Meningiomas of the cerebellopontine angle (CPA) share a common
      location, but their site of dural origin and their relationship to surrounding
      neurovascular structures of the CPA are variable. The clinical presentation and
      outcome after surgical resection are different because of the diversity of this
      tumor entity. We report on a series of 421 patients with CPA meningiomas, with
      special emphasis on the analysis of the preoperative and postoperative facial and
      cochlear nerve function in relation to the site of dural attachment and main
      tumor location in the CPA cistern. METHODS: Among 421 patients, the charts of 347
      patients with complete clinical data, including the history and audiograms,
      imaging studies, surgical records, discharge letters, histological records, and
      follow-up records, were reviewed retrospectively. Data about preoperative and
      postoperative facial nerve function were available in 334 patients, and
      audiometric analysis was conducted in 333 patients. Patients with
      neurofibromatosis Type 2 were excluded from the study. RESULTS: There were 270
      women and 77 men, with a mean age of 53.4 years (range, 17.6-84 yr). Among these
      patients, 32.9% of the tumors originated at the petrous ridge anterior to the
      inner auditory canal (IAC) (Group 1), 22.2% showed involvement of the IAC (Group
      2), 20.2% were located superior to the IAC (Group 3), 11.8% were inferior to the
      IAC (Group 4), and 12.9% were posterior to the IAC, originating between the IAC
      and the sigmoid sinus (Group 5). Patients presented with disturbance of Cranial
      Nerves V-VIII, the lower cranial nerves, and ataxia, depending on the main tumor
      location. Tumor resection was performed through a suboccipital-retrosigmoidal
      approach in the semisitting position in 95% of the patients. A combined
      supratentorial-infratentorial presigmoidal approach was performed in 5%. Total
      tumor removal (Simpson Grade 1 and 2) was achieved in 85.9% and subtotal removal
      in 14.1%. The best initial postoperative facial and auditory nerve function was
      observed in tumors belonging to Groups 3 and 5. Recovery from preoperative
      deafness was observed in 1.8% of patients. On long-term follow-up, good facial
      nerve function (House-Brackmann Grade 1 or 2) was observed in 88.9% of patients.
      Hearing preservation among patients with preoperative functional hearing was
      documented in 90.8% on long-term follow-up. CONCLUSION: Although the outcome of
      facial and cochlear nerve function is different in CPA meningiomas, depending on
      the topographic classification of these tumors, preservation of the cochlear
      nerve is possible in every tumor group and should be attempted in every patient
      with CPA meningioma. It has to be kept in mind that recovery of hearing was also
      observed in patients with preoperative profound hearing deficits.

PMID- 15987544
TI  - Clinical features and long-term results of spontaneous intracranial hypotension.
AB  - OBJECTIVE: Although spontaneous intracranial hypotension (SIH) is an increasingly
      recognized syndrome, the long-term outcomes have not been established. We
      conducted a long-term follow-up study to clarify the clinical features and long
      term outcomes of patients with this disorder. METHODS: We performed a
      retrospective study in 13 consecutive patients with SIH treated between 1998 and
      2003. The diagnosis of intracranial hypotension was made on the basis of clinical
      symptoms, lumbar puncture, radiological studies (e.g. brain magnetic resonance
      imaging, spine magnetic resonance imaging, computed tomographic myelography) and
      radionuclide cisternography. We collected follow-up clinical information of the
      patients by telephone or by examination at an outpatient clinic. RESULTS: All
      patients were treated by nonsurgical conservative treatments, such as absolute
      bed rest, intravenous hydration and repetitive epidural blood patch (5 patients).
      The mean duration of follow up was 51.4 months (range, 15-80 mo). Among 13
      patients included in this study, only one patient (7.7%) developed recurrent SIH,
      and the other patients improved from orthostatic headache. Although 7 of 13
      patients had complete resolution of headache at a minimum of 2 years follow-up, 4
      patients had mild headache and 2 patients continued to have moderate headache at
      the final examination. CONCLUSION: In this series, the outcome of SIH after
      conservative treatment was not as satisfactory as that reported in previous
      studies. We conclude that periodic follow-up examinations must be performed and a
      more effective treatment modality developed to achieve complete resolution of
      SIH.

PMID- 15987545
TI  - Rapidly rising incidence of cerebrospinal fluid shunting procedures for
      idiopathic intracranial hypertension in the United States, 1988-2002.
AB  - OBJECTIVE: Obesity, a major risk factor for idiopathic intracranial hypertension
      (IIH), is rapidly increasing in all ages of the United States population. We
      studied trends in the incidence of cerebrospinal fluid (CSF) shunts for IIH in
      the United States between 1988 and 2002, using a national hospital discharge
      database. METHODS: This was a retrospective study using the Nationwide Inpatient
      Sample and robust weighted least-squares regression, adjusted for stratified
      survey methodology. RESULTS: There were 2779 admissions for CSF shunting
      procedures (new or revision) in IIH patients in the database. In-hospital
      mortality for new shunts was 0.5% (0.9% for ventricular shunts and 0.2% for
      lumbar shunts). The estimated total United States caseload of CSF shunting
      procedures for IIH increased 350% between 1988 and 2002 (P < 0.001). (The 2002
      United States caseload was 1370 admissions). New shunt placements increased 320%
      during this interval (P < 0.001). In some subpopulations in which obesity is less
      important as a risk factor for IIH, caseload increases were less marked:
      pediatric IIH shunting (age < 13 yr) increased 52% and shunting in male IIH
      patients increased 38%, but shunting in older patients (age > 44 yr) increased
      240% during the study period. Bariatric procedures (e.g., gastric bypass)
      increased very rapidly in incidence since 1998, with nearly 200 such procedures
      performed on IIH patients in 2002. CONCLUSION: The incidence of CSF shunting for
      IIH is increasing in the population of the United States at about the same
      relative rate as morbid obesity. Studies to establish the best shunting method in
      IIH and to explore alternative treatment strategies, such as optic nerve sheath
      fenestration and bariatric surgery, are urgently needed.

PMID- 15987546
TI  - Gravitational shunts in longstanding overt ventriculomegaly in adults.
AB  - OBJECTIVE: A new entity of chronic hydrocephalus was introduced recently in the
      international literature: longstanding overt ventriculomegaly in adults. Previous
      experience with this disorder has demonstrated that shunt therapy for such
      patients involves a considerable risk of overdrainage. In the present study, we
      aimed to clarify whether this risk could be avoided by use of gravitational
      shunts. METHODS: A total of 26 adults (age range, 17-75 yr) with macrocephaly and
      progressive hydrocephalus symptoms underwent implantation of either an adjustable
      Codman Hakim gravity-assisted shunt (Codman Medos, LeLocle, Switzerland) plus an
      Aesculap-Miethke ShuntAssistant (Miethke KG, Kleinmachnow, Germany) or a
      nonadjustable gravitational shunt (Aesculap-Miethke gravity-assisted valve). The
      follow-up period averaged 29 +/- 13 months (range, 6-48 mo). RESULTS: Significant
      sustained clinical improvement was achieved in 87% of patients. In more than 90%
      of patients, Evans index decreased postoperatively by less than 10%. No
      correlation was documented between the degree of ventricle width reduction and
      clinical improvement. Only two patients developed subdural hematoma, which was
      caused by insufficient hydrostatic pressure compensation owing to errors in
      estimation of intraperitoneal pressure. CONCLUSION: Unlike conventional
      differential pressure shunts, gravitational shunts can be used in the treatment
      of high-risk patients with longstanding overt ventriculomegaly in adults.
      Significant risk of overdrainage can be avoided. Gravitational shunts offer a
      viable alternative to endoscopic third ventriculostomy, provided the choice and
      adjustment of the shunt opening pressure is based on a correct assessment of the
      hydrostatic pressure to be compensated for.

PMID- 15987547
TI  - Management and outcomes of 42 surgical suprascapular nerve injuries and
      entrapments.
AB  - OBJECTIVE: Retrospective chart reviews of 42 patients with surgical suprascapular
      nerve (SSN) injury/entrapment were performed. Presenting symptoms, findings,
      operative approach, and results are documented. METHODS: Forty-two patients with
      SSN injuries/entrapments underwent operations between 1970 and 2002. Charts were
      retrospectively reviewed for the presence of shoulder pain; spinati muscle
      function was evaluated with the Louisiana State University Health Sciences Center
      grading system. Side of lesion and sex were equally represented; mean follow-up
      was 18 months (range, 12-48 mo). SSN injuries/entrapments were associated with
      occupational overuse, sports-related injury, direct trauma and ganglion cysts.
      Thirty-one (79%) of 39 patients with suprascapular notch SSN
      injuries/entrapments, excluding ganglion cysts, presented with mild to moderate
      shoulder pain and spinati weakness. RESULTS: Motor function for these 31 patients
      was graded on a scale of 0 to 5. Preoperatively, patients had supraspinatus
      function Grades 0 to 2 and infraspinatus function Grades 0 to 2. Supraspinatus
      function improved postoperatively to Grade 4 or better in 28 patients (90%) and
      to Grades 2 to 3 in 3 patients (10%). Infraspinatus function improved to better
      than Grade 3 in 10 patients (32%), to Grades 2 to 3 in 14 patients (45%), and to
      Grade 1 in 7 patients (23%). Preoperatively, eight (21%) of 39 patients
      presenting with persistent severe pain had Grade 3 spinati strength. Of these
      eight patients, seven (88%) had an improvement in pain postoperatively. Strength
      in this group remained the same or improved to Grade 4. Postoperatively, three
      patients with ganglion cysts had good improvement in spinati function.
      CONCLUSION: Although SSN injury/entrapment is rare, 42 patients are presented who
      responded well to SSN release. Supraspinatus muscle improvement was as good as or
      better than that achieved in the infraspinatus.

PMID- 15987548
TI  - Chronic traumatic encephalopathy in a National Football League player.
AB  - OBJECTIVE: We present the results of the autopsy of a retired professional
      football player that revealed neuropathological changes consistent with long-term
      repetitive concussive brain injury. This case draws attention to the need for
      further studies in the cohort of retired National Football League players to
      elucidate the neuropathological sequelae of repeated mild traumatic brain injury
      in professional football. METHODS: The patient's premortem medical history
      included symptoms of cognitive impairment, a mood disorder, and parkinsonian
      symptoms. There was no family history of Alzheimer's disease or any other head
      trauma outside football. A complete autopsy with a comprehensive
      neuropathological examination was performed on the retired National Football
      League player approximately 12 years after retirement. He died suddenly as a
      result of coronary atherosclerotic disease. Studies included determination of
      apolipoprotein E genotype. RESULTS: Autopsy confirmed the presence of coronary
      atherosclerotic disease with dilated cardiomyopathy. The brain demonstrated no
      cortical atrophy, cortical contusion, hemorrhage, or infarcts. The substantia
      nigra revealed mild pallor with mild dropout of pigmented neurons. There was mild
      neuronal dropout in the frontal, parietal, and temporal neocortex. Chronic
      traumatic encephalopathy was evident with many diffuse amyloid plaques as well as
      sparse neurofibrillary tangles and tau-positive neuritic threads in neocortical
      areas. There were no neurofibrillary tangles or neuropil threads in the
      hippocampus or entorhinal cortex. Lewy bodies were absent. The apolipoprotein E
      genotype was E3/E3. CONCLUSION: This case highlights potential long-term
      neurodegenerative outcomes in retired professional National Football League
      players subjected to repeated mild traumatic brain injury. The prevalence and
      pathoetiological mechanisms of these possible adverse long-term outcomes and
      their relation to duration of years of playing football have not been
      sufficiently studied. We recommend comprehensive clinical and forensic approaches
      to understand and further elucidate this emergent professional sport hazard.

PMID- 15987549
TI  - Resorbable polylactic acid interbody spacers with vertebral autograft for
      anterior cervical discectomy and fusion.
AB  - OBJECTIVE: Resorbable polylactic acid spinal implants have recently become
      commercially available. These spacers carry the advantages of allowing for clear
      visualization of new bone growth, eliminating the risk of pathogen transmission,
      and providing for consistent biomechanical quality. However, previously published
      reports on the use of these spacers have all utilized bone morphogenetic proteins
      to supplement the fusion. This report describes our early experience with the use
      of these devices for interbody reconstruction in anterior cervical discectomy
      with fusion. METHODS: Twenty patients underwent an anterior cervical discectomy
      with fusion at 30 levels during an 18-month period. All patients were implanted
      with polylactic acid interbody spacers using the Smith-Robinson technique.
      Supplementary anterior cervical plating was applied using unicortical
      semiconstrained screws, and the spacers were filled with vertebral endplate
      autograft bone shavings. Seven of the patients were smokers, and three were
      diabetics. Radiographic fusion was determined with dynamic cervical spine x-rays,
      and clinical responses were determined using the Medical Outcomes Study Short
      Form 36-Item Health Survey, Odom's criteria, Nurick scores, and functional
      outcome swallowing score dysphagia scores. Follow-up averaged 11.6 months.
      RESULTS: Of the 9 patients with myelopathy, all experienced clinical improvement,
      with the mean Nurick score improving from 2.7 to 1.3. Of the 14 patients who had
      radiculopathy, 9 had complete resolution of symptoms, 4 experienced some
      improvement, and 1 had no improvement. All 20 patients demonstrated radiographic
      fusion at last follow-up as demonstrated by bridging bone between the vertebral
      bodies and the absence of motion on dynamic x-rays. CONCLUSION: Resorbable
      polylactic acid interbody spacers are safe and effective for anterior cervical
      discectomy and fusion. Use of locally harvested vertebral endplate bone packed
      within the spacer is sufficient to promote fusion in anterior cervical discectomy
      with fusion.

PMID- 15987550
TI  - Potent mimicry of fibronectin-induced intracellular signaling in glioma cells by
      the homodimeric snake venom disintegrin contortrostatin.
AB  - OBJECTIVE: The snake venom disintegrin contortrostatin (CN) is able to inhibit
      tumor progression and angiogenesis in vivo and therefore is of considerable
      interest as a potential antitumor drug. CN specifically binds to certain
      integrins on the tumor cell and angiogenic endothelial cell surface and inhibits
      their interaction with the extracellular matrix, resulting in blockage of cell
      motility and invasiveness. To understand the molecular consequences of CN binding
      to integrins, we set out to investigate and compare the effects of CN and
      fibronectin (FN) on integrin-induced signaling and the resulting alteration in
      cellular cytoskeletal morphology. METHODS: Two different malignant glioma cell
      lines were exposed to soluble or immobilized CN, FN, or both, and the
      consequences for intracellular signaling and cellular adhesion to matrix were
      investigated. RESULTS: CN binding to integrins can mimic the intracellular
      signaling cascade evoked by FN, because the phosphorylation of the key signaling
      proteins focal adhesion kinase, paxillin, and p130 Crk-associated substrate and
      the association of Src with focal adhesion kinase are similar. However, CN is at
      least one order of magnitude more potent than FN. When soluble CN is added to
      cells that are already attached to an FN-coated matrix, it effectively disrupts
      the binding of integrin to FN, leading to a decrease in integrin signaling,
      which, in turn, results in the disruption of the cytoskeleton and cellular
      detachment. CONCLUSION: Our results provide a mechanistic explanation of how
      soluble CN might block cellular migration and invasion, namely, by disrupting and
      preventing the binding of integrins to the extracellular matrix. We envision that
      this property of CN could be used in the treatment of gliomas, namely, by
      intratumoral infusion of CN to prevent glioma and endothelial cell interactions
      with the extracellular matrix, leading to inhibition of cell invasion.

PMID- 15987551
TI  - Correlation of hippocampal morphological changes and morris water maze
      performance after cortical contusion injury in rats.
AB  - OBJECTIVE: The hippocampus is essential to the processing and formation of
      memory. This study analyzed the relationship among memory dysfunction as revealed
      by Morris water maze (MWM) trial, cortical lesion volume, and regional
      hippocampal morphological changes after controlled cortical contusion (CCC). We
      also analyzed the influence of pretreatment with the nitrone radical scavenger
      alpha-phenyl-N-tert-butyl-nitrone (PBN). METHODS: Rats were subjected to CCC. We
      used two levels of CCC (mild, 1.5 mm and severe, 2.5 mm) and pretreated some
      severely injured animals with PBN. The animals were killed 15 days postinjury. We
      evaluated morphological changes to the hippocampus semiquantitatively by scoring
      sections immunohistochemically stained for microtubule-associated protein 2 with
      a four-point scale for the cornu ammonis (CA) 1, CA2, CA3, and hilus of the
      dentate gyrus (HDG). The cortical lesion volume was quantified. RESULTS: Rats
      subjected to severe, but not mild, CCC demonstrated impaired spatial learning
      ability in the MWM, but this impairment was attenuated with pretreatment with the
      radical scavenger PBN. We documented bilateral morphological changes in CA1, CA3,
      and HDG and an ipsilateral neocortical cavitation in severely injured rats. PBN
      treatment attenuated (P < 0.05) the morphological characteristics of abnormality
      in the ipsilateral CA1, CA2, HDG, and the contralateral HDG and reduced the
      cortical lesion volume. Mild injury led to minor ipsilateral hippocampal and
      cortical damage but no MWM deficiency. Hippocampal morphological scores and total
      mean latencies in the MWM task were strongly correlated (r = 0.69; P < 0.001).
      The correlation between the cortical lesion volume and MWM latency was weaker (r
      = 0.48; P = 0.02). CONCLUSION: Severe CCC causes bilateral morphological changes
      in the hippocampus and ipsilateral neocortical cavitation, which correlate to
      impairment in a spatial learning task (MWM). PBN protected the structure of the
      CA2 ipsilaterally and HDG bilaterally and reduced the cortical lesion volume,
      correlating to improved functional outcome.

PMID- 15987553
TI  - Neurosurgery at Tribhuvan University Teaching Hospital, Nepal.
AB  - February 6, 2005, marks the 10th anniversary of the first neurosurgical procedure
      performed at Tribhuvan University Teaching Hospital, one of only a few tertiary
      care hospitals in Nepal. Neurosurgery began at the hospital with the arrival of
      an American neurosurgeon to train Nepalese surgeons locally and, later, the
      return of these Nepalese surgeons to Kathmandu after subsequent fellowship
      training in the United States. This article traces the origins of neurosurgery in
      Nepal, outlines the specialty's development in Kathmandu at Tribhuvan University
      Teaching Hospital during the past decade from international education strategies,
      and describes the status of and challenges facing the provision of neurosurgical
      care in Nepal. The role of neurosurgical services in improving the health care
      status of populations in developing countries is considered. Neurosurgeons in
      developing and developed countries alike should continue to work to remedy the
      inequitable distribution of neurosurgical knowledge and services throughout the
      world.

PMID- 15987552
TI  - Hypothesis of the postconcussive vulnerable brain: experimental evidence of its
      metabolic occurrence.
AB  - OBJECTIVE: We evaluated the effects of two consecutive concussive injuries on
      brain energy metabolism and N-acetylaspartate (NAA) to investigate how the
      temporal interval between traumatic events influences overall injury severity.
      METHODS: Rats were injured to induce diffuse traumatic brain injury (TBI) (mild,
      450 g/1 m; severe, 450 g/2 m). In two groups, two mild TBIs were delivered in 3-
      or 5-day intervals. Three additional animal groups were used: single mild TBI,
      single severe TBI, and sham. All animals were killed 48 hours postinjury.
      Adenosine 5'-triphosphate (ATP), adenosine diphosphate, and NAA concentrations
      were analyzed with high-performance liquid chromatography on deproteinized whole
      brain extracts. RESULTS: In control animals, the NAA concentration was 9.17 +/-
      0.38 micromol/g wet weight, the ATP concentration was 2.25 +/- 0.21 micromol/g
      wet weight, and the ATP-to-adenosine diphosphate ratio was 9.38 +/- 1.23. These
      concentrations decreased to 6.68 +/- 1.12 micromol/g wet weight, 1.68 +/- 0.24
      micromol/g wet weight, and 6.10 +/- 1.21 micromol/g wet weight, respectively, in
      rats that received two mild TBIs at a 5-day interval (P < 0.01; not different
      from results in rats with single mild TBI). When a second TBI was delivered after
      3 days, the NAA concentration was 3.86 +/- 0.53 micromol/g wet weight, the ATP
      concentration was 1.11 +/- 0.18 micromol/g wet weight, and the ATP-to-adenosine
      diphosphate ratio was 2.64 +/- 0.43 (P < 0.001 versus both controls and 3-day
      interval; not different from rats receiving a single severe TBI). CONCLUSION: The
      biochemical modification severity in double TBI is dependent on the interval
      between traumatic events, which demonstrates the metabolic state of the
      vulnerable brain after mild TBI. These data support the hypothesis of the
      application of proton magnetic resonance spectroscopy to measure NAA as a
      possible tool to monitor the full recovery of brain metabolic functions in the
      clinical setting, particularly in sports medicine.

PMID- 15987554
TI  - Hippocrates: a pioneer in the treatment of head injuries.
AB  - Hippocrates' treatise On Wounds in the Head represents an excellent source of
      information regarding the extent of experience with head injuries in classical
      antiquity. On the basis of clinical observation, the great physician gives an
      accurate description of the external appearance and consistency of the cranium.
      Fractures of the cranium are divided into six main categories, each of which is
      discussed separately, regarding its mechanism, clinical assessment, and
      treatment. The medical history and clinical evaluation are considered the most
      important factors when dealing with cranial trauma. Trepanation, a neurosurgical
      procedure still in practice today, is presented in detail. As a whole, the
      treatise, the first written work in medical history dealing exclusively with
      cranial trauma, reveals that Hippocrates was a pioneer in treating head injuries.

PMID- 15987555
TI  - Optic nerve glioma and optic neuritis mimicking one another: case report.
AB  - OBJECTIVE AND IMPORTANCE: The clinical and radiographic presentations of optic
      nerve gliomas and optic neuritis are for the most part distinct and their
      diagnoses straightforward. We present two cases illustrating the occasional
      difficulty one can encounter in distinguishing neoplastic from inflammatory optic
      neuropathies. CLINICAL PRESENTATION: Patient 1 is a 17-year-old girl who
      presented with acute onset of pain and rapidly progressive visual loss in the
      right eye. Patient 2 is a 38-year-old man who presented with painless progressive
      visual loss in the left eye. INTERVENTION: Patient 1 was initially diagnosed with
      idiopathic retrobulbar optic neuritis. Interval increase of the optic nerve on
      magnetic resonance imaging prompted a biopsy of the optic nerve, which revealed a
      pilocytic astrocytoma. Patient 2 was found to have left optic nerve enhancement
      most consistent with an optic nerve glioma. Before a biopsy, the patient
      spontaneously improved without treatment, indicating an inflammatory process.
      CONCLUSION: Differentiating between optic nerve neoplasm and inflammation may be
      difficult. On occasion, the classic clinical finding of pain with eye movement
      and the radiographic finding of enlargement and enhancement of the optic nerve
      may be misleading. Open biopsy of the optic nerve is indicated only after a
      completely negative metabolic, infectious, and inflammatory workup; interval
      increase of the optic nerve on magnetic resonance imaging; and failure of the
      patient to recover vision.

PMID- 15987556
TI  - Synchronous multicentric pleomorphic xanthoastrocytoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Pleomorphic xanthoastrocytoma (PXA) is a rare, low
      grade astrocytoma of adolescence. Relatively favorable outcomes have been
      achieved with complete surgical resection. However, few data exist regarding the
      treatment of recurrent, deep-seated, or multicentric lesions. We report the first
      case to our knowledge of synchronous multicentric PXA and discuss the related
      therapeutic challenges. CLINICAL PRESENTATION: A 13-year-old Hispanic girl
      presented with a 1-year history of progressive headaches, polyuria, and
      generalized fatigue. Findings from the neurological examination were notable only
      for the presence of papilledema. Results of laboratory studies revealed diabetes
      insipidus and hypothyroidism. The magnetic resonance imaging study revealed
      numerous nodular, homogeneously enhancing lesions, approximately 1 cm in size,
      scattered throughout both cerebral hemispheres. INTERVENTION: A right frontal
      craniotomy was performed for excisional biopsy of a superficial lesion beneath
      the coronal suture. Results of the histological examination were consistent with
      a diagnosis of PXA. The patient was treated with whole-brain radiation of 3600
      cGy, with additional intensity-modulated boosts to the enhancing lesions of 1440
      cGy. Three years after treatment, the patient remains neurologically nonfocal and
      shows no evidence of disease progression. Surgical intervention will be
      considered if accessible lesions progress in size on later imaging studies.
      CONCLUSION: Synchronous multicentric PXA presents unique challenges in that gross
      total resection would impose significant surgical morbidity; histological
      homogeneity among the lesions cannot be confirmed; and the well-described
      potential for anaplastic transformation may be increased with multiple lesions.
      The optimal treatment for patients with this rare and challenging diagnosis
      awaits further study.

PMID- 15987557
TI  - Supratentorial cortical ependymoma: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: Extraventricular ependymomas account for 50% of
      supratentorial ependymomas. Some tumors may extend to the gray matter reaching
      the pial surface, but pure cortical ependymomas are uncommon. Here, we report
      three patients with supratentorial intracortical ependymoma. CLINICAL
      PRESENTATION: We reviewed the clinicopathological findings of all patients
      operated on for ependymomas at the Bellaria Hospital during an 11-year period and
      found three lesions described as cortical ependymomas. The three lesions
      represented 2.5% of all ependymal tumors and 21.4% of supratentorial tumors
      operated on during the study period. The patient were aged 52, 24, and 11 years
      (mean, 32.3 yr). One was female. All presented with seizures. On imaging, the
      lesions were confined to the gray matter, were solid, and demonstrated diffuse
      enhancement. INTERVENTION: Gross total resection was achieved in all instances.
      Two patients were treated with surgery, and one was treated with surgery and
      postoperative radiotherapy. All tumors were low grade. After a mean follow-up of
      92.6 months, no patient had recurrence or leptomeningeal dissemination. Review of
      preoperative magnetic resonance imaging scans confirmed an intracortical
      location. Routine sections were reviewed, and additional immunoreactions for
      epithelial membrane antigen, glial fibrillary acidic protein, synaptophysin,
      neurofilament proteins, S-100 protein, and Ki-67 and electron microscopy were
      performed. CONCLUSION: Cortical ependymomas seem to behave as benign tumors
      amenable to surgical removal. Local recurrence and leptomeningeal dissemination
      seem to be unlikely. Postoperative radiotherapy is unnecessary.

PMID- 15987558
TI  - Hydatid cyst of the craniocervical junction: case report.
AB  - OBJECTIVE AND IMPORTANCE: Although rare in developed countries, hydatid disease
      is a serious parasitic infection in endemic areas. Spinal disease most commonly
      involves the thoracic region, and involvement of the upper cervical spine is
      extremely rare. In this report, a case of hydatid disease involving the
      craniocervical junction is presented, along with a review of the literature.
      CLINICAL PRESENTATION: A 44-year-old man presented with the complaint of neck
      pain. The results of his physical and neurological examinations were within
      normal ranges, except for pain exacerbated by neck motion and spasm of the
      cervical musculature. Magnetic resonance imaging demonstrated a cystic lesion
      involving the odontoid process and body of C1 and C2, with thin and regular cyst
      walls and cyst contents similar in intensity to that of cerebrospinal fluid. The
      results of serological tests performed with the suspected diagnosis of hydatid
      disease were positive. INTERVENTION: The patient initially underwent surgery to
      provide stabilization of the craniocervical junction, using autogenous bone graft
      and sublaminar wiring from the occiput to C3 via a posterior approach. The cyst
      was approached via a transoral route, using a U-shaped pharyngeal incision. There
      were no neurological deficits after surgery. Postoperative magnetic resonance
      imaging scans confirmed complete excision of the cyst, and the patient was
      discharged on the 12th postoperative day. He received six cycles of albendazole
      treatment, each consisting of 28 days with an intervening drug-free period of 2
      weeks. Magnetic resonance imaging scans performed 1 year after surgery revealed
      the patient was still disease-free. CONCLUSION: Hydatid disease should be
      considered in the differential diagnosis of spinal cord compression, especially
      in endemic areas. Although the chance of obtaining a cure is unlikely, radical
      surgery coupled with antihelminthic therapy seems to provide long-lasting relief.

PMID- 15987559
TI  - Fusion around cervical disc prosthesis: case report.
AB  - OBJECTIVE AND IMPORTANCE: Cervical arthroplasty is a relatively new method to
      maintain motion after cervical anterior discectomy. Two cases are presented in
      which bony fusion occurred around a cervical disc prosthesis. CLINICAL
      PRESENTATION: A 30-year-old man and a 49-year-old woman underwent a right-sided
      anterior cervical discectomy because of pain in the right arm resulting from a
      herniated disc (C5-C6). INTERVENTION: A cervical disc prosthesis (Bryan disc
      prosthesis) was implanted. Postoperatively, the patients were completely free of
      pain. At the regular 1- and 2-year follow-up examinations, bony fusion was seen
      on plain x-rays of the cervical spine. The patients were still completely free of
      signs and symptoms. CONCLUSION: This is the first report in the literature of
      bony fusion after cervical arthroplasty with the Bryan disc prosthesis.

PMID- 15987560
TI  - Spinal solitary fibrous tumors: a series of four patients: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intraspinal solitary fibrous tumors, which are rare
      mesenchymal tumors, have previously been reported as case reports. We review our
      experience and, to our knowledge, the first small institutional series with
      respect to clinical presentation, diagnosis, surgical management,
      pathohistological analysis, progression-free survival, and long-term outcome.
      CLINICAL PRESENTATION: In this retrospective review, four patients (three male
      and one female) ranging in age from 17 to 59 years (mean, 38.5 yr) had spinal
      solitary fibromas located throughout the spinal canal. Three tumors were located
      in the thoracic region and one in the cervical spine. All patients presented with
      pain and paresthesia. Two patients had an associated spinal deformity. All had
      gross total resection as confirmed by postoperative imaging studies.
      INTERVENTION: All four patients underwent surgical treatment for spinal solitary
      fibromas. None of these patients underwent irradiation or chemotherapy after
      surgery at our center; therefore, outcome was attributed to surgery alone. There
      were no surgical deaths, and the 5-year actuarial survival rate was 100%. At the
      most recent follow-up examination, neurological function was stable or improved
      in 90% of patients. CONCLUSION: Patients with solitary fibrous tumors have a long
      survival. These tumors have an indolent course, and radiotherapy or chemotherapy
      seems to be unnecessary.

PMID- 15987561
TI  - Primary isolated amyloidoma of the lumbar spine causing neurological compromise:
      case report and literature review.
AB  - OBJECTIVE AND IMPORTANCE: We describe a patient with cauda equina compression
      secondary to amyloidoma to alert other clinicians to this rare cause of a
      compressive epidural lesion. It is the fourth published report of primary lumbar
      amyloidoma causing neurological compromise. CLINICAL PRESENTATION: A 53-year-old,
      previously fit salesman presented with several years history of back pain and
      recent weakness, especially in the left leg. He also had numbness and tingling
      radiating down the left leg. On examination, the left knee jerk was diminished,
      and both ankle jerks were absent. Power was reduced to 4/5 in ankle dorsiflexion
      bilaterally. A magnetic resonance imaging scan of the lumbar spine revealed an
      extradural mass, compressing the theca at L3-L4. This was enhancing in T1
      weighted images and had low signal intensity in T2-weighted images. There was no
      evidence of systemic amyloidosis or development of multiple myeloma.
      INTERVENTION: L3-L4 laminectomy was performed, with removal of the epidural mass.
      The patient had complete resolution of sciatica and regained normal power in both
      lower limbs. There was no evidence of any recurrence at 1-year follow-up.
      CONCLUSION: Lumbar epidural amyloidoma is an extremely rare cause of cauda equina
      compression. Clinical presentation can be nonspecific, and radiologically, it can
      be indistinguishable from a tumor. Diagnosis is made at histological examination
      of a Congo red-stained section under polarized light. Complete resection of the
      localized epidural amyloid mass is associated with a good prognosis.

PMID- 15987562
TI  - Lateral sacral artery aneurysm: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: We report the third case of an aneurysm of the lateral
      sacral artery (AnLSA). In all cases, because of an incorrect preoperative
      diagnosis, the surgeons were confronted with severe and unexpected hemorrhaging,
      and surgery was aborted without effective treatment. Our purpose is to present
      the preoperative features of AnLSA and its treatment modalities. CLINICAL
      PRESENTATION: A 54-year-old man had a medical history of renal transplantation on
      his left external iliac artery. He complained of acute lumbar pain associated
      with cauda equina syndrome, which resolved within a few hours. At that time, a
      magnetic resonance imaging (MRI) scan revealed an intracanal hematoma extending
      from S1 to T12. Six weeks later, a second MRI scan demonstrated an oval-shaped
      intracanal mass behind the vertebral body of S1 with intense gadolinium
      enhancement. INTERVENTION: An anterior epidural mass was found. An incision into
      this mass resulted in significant arterial hemorrhaging. Transparietal
      embolization with a cotton compress and closure of the aneurysm wall were
      performed. The postoperative clinical status was stable, and a delayed
      angiographic study suggested a diagnosis of aneurysm of the right LSA, a branch
      of the internal iliac artery. Its pathophysiology was explained by the
      development of a high-flow transpelvic shunt from the right iliac artery
      territory to the left, to maintain the renal graft blood flow that had initially
      been reduced by stenosis of the left common iliac artery. Six weeks later, a new
      MRI scan demonstrated that the AnLSA had increased in size. The lesion was then
      excluded endovascularly by injection of glue. CONCLUSION: A medical history of
      renal transplantation with MRI scans showing an anterior epidural mass behind S1
      or a spontaneous spinal epidural hematoma are features that must evoke a
      diagnosis of AnLSA. Treatment is mandatory and is best achieved by embolization.
      Surgery based on angiographic findings is indicated if the lesion is responsible
      for a compressive hematoma.

PMID- 15987563
TI  - Evaluation of the portable infrared pupillometer.

PMID- 15987564
TI  - Dexmedetomidine for neurological surgery.
AB  - Dexmedetomidine is a new intravenous drug gaining popularity in neuroanesthesia
      and neurocritical care practice. This alpha2-adrenergic receptor agonist offers a
      unique "cooperative sedation," anxiolysis, and analgesia with no respiratory
      depression. Cerebral effects are generally consistent with a desirable
      neurophysiological profile, including neuroprotective characteristics. In
      addition, sympatholytic and antinociceptive properties allow for hemodynamic
      stability at critical moments of neurosurgical stimulation. This review will
      address the neuropharmacology and neurophysiology of alpha2-adrenergic agonists
      and will specifically consider the rapidly evolving applicability of
      dexmedetomidine as an adjuvant to neurosurgical case management.

PMID- 15987565
TI  - Vascular anatomy of the anteriorly based pericranial flap.
AB  - OBJECTIVE: The purpose of this study was to examine the vascular supply of the
      anteriorly based frontal pericranial flap to determine whether separating the
      pericranium from the galea above the orbital rim would devascularize the
      pericranial flap. METHODS: The arteries supplying and the veins draining the
      frontal pericranial flap were examined in 17 adult cadavers using x3 to x30
      magnification. The arteries were examined on 25 sides and the veins on 16 sides.
      RESULTS: The main trunk and superficial branches of the supraorbital and
      supratrochlear arteries, which course in the galea-frontalis muscle layer, give
      rise to the deep branches that supply the pericranium. These pericranial branches
      may arise in the orbit or at the level of or above the orbital rim. Pericranial
      arteries that arose above the level of the orbital rim and would be divided in
      separating the galea and pericranium were found in 28% of the sides examined.
      Pericranial veins that coursed above the orbital rim and would be divided in
      separating the galea-frontalis muscle layer from the pericranial layer were found
      in 43.8% of the sides examined. CONCLUSION: In preparing a pericranial flap based
      anteriorly on the supraorbital rim, the separation of the galea-frontalis muscle
      layer from the pericranium layer should not extend into the 10 mm above the
      supraorbital rim if the arterial and venous pedicle of the pericranial flap is to
      be preserved.

PMID- 15987566
TI  - Microsurgical anatomic features of the olfactory nerve: relevance to olfaction
      preservation in the pterional approach.
AB  - OBJECTIVE: The pterional approach represents the standard approach for most
      lesions of the anterior and middle cranial fossa. It requires some degree of
      frontal lobe retraction, which may result in temporary or permanent damage of
      olfaction because of nerve avulsion or mechanical compression. The purpose of
      this study, based on microanatomic dissection of human cadaveric specimens, was
      to review the microsurgical anatomic features of the nerve and suggest operative
      nuances that may contribute to reducing the rate of postoperative olfactory
      dysfunction. METHODS: Twenty olfactory nerves and tracts were examined in 10
      human cadaveric heads obtained from three fresh and seven formalin-fixed adult
      cadavers. A standard pterional craniotomy was performed. The olfactory nerve was
      dissected from its arachnoidal envelopes and then mobilized for an average length
      of 30 mm (range, 25-35 mm). RESULTS: The possible retraction of the frontal lobe
      was 10 to 15 mm. More retraction invariably resulted in nerve disruption.
      CONCLUSION: The standard sylvian and basal cistern opening may be insufficient to
      guarantee preservation of olfactory function. Early identification and
      arachnoidal dissection of the nerve may reduce the rate of olfaction compromise.
      The opening of the subarachnoidal space should be performed in a proximal-to
      distal manner to allow early visualization of the olfactory bulb and its
      dissection. The arachnoidal dissection should be performed with sharp
      instruments, avoiding any traction on the posterior portion of the olfactory
      tract. Any direct retractor compression should also be avoided to spare the
      microvasculature lying on the dorsal surface of the nerve.

PMID- 15987567
TI  - Microanatomy of the intrachoroidal vasculature of the lateral ventricle.
AB  - OBJECTIVE: Intraventricular surgery requires a detailed knowledge of the
      microanatomy of the choroid plexus vasculature. METHODS: Twenty choroid plexuses
      were microdissected, and two additional plexuses were prepared for microscopic
      examination. RESULTS: The choroid plexus was perfused primarily by the anterior
      choroidal artery (AChA) and the lateral posterior choroidal artery (LPChA). The
      AChA, which averaged 650 microm in diameter, most often (in 75% of cases) divided
      into the medial and lateral trunks, which averaged 450 microm in diameter. The
      medial trunk gave off the bush-like intrachoroidal branches, whereas the lateral
      trunk divided into the parallel arteries. The inferior LPChA was present in 50%
      of the hemispheres, both the inferior and superior LPChAs in 40%, and their
      common trunk in 10%. In 40%, the LPChA, which averaged 670 microm in diameter,
      divided into the terminal trunks, with a mean diameter of 490 microm. The
      anastomoses involving the trunks of the LPChA and other choroidal arteries
      averaged 310 microm in diameter. All primary intrachoroidal branches of the AChA
      and LPChA were divided into three groups. The parallel branches, which averaged
      from 220 to 230 microm in diameter, coursed along the lateral part of the choroid
      plexus. The tortuous glomus vessels, which averaged 310 microm in size,
      originated from the AChA (45%), the LPChA (15%), or both (40%). The bush-like
      vessels, with a mean diameter between 155 and 190 microm, ramified into smaller
      twigs, up to the intrachoroidal capillaries. CONCLUSION: The data obtained on the
      microanatomy of the intrachoroidal vasculature may have certain neurosurgical
      implications.

PMID- 15987568
TI  - Anatomic analysis of the transforaminal ligament in the lumbar intervertebral
      foramen.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical significance
      of the transforaminal ligaments (TFLs) in relation to the area of the lumbar
      intervertebral foramen (IVF) by analyzing cadaveric spines. METHODS: One hundred
      ninety-eight cadaveric lumbar IVFs were studied, and the existence and type of
      TFLs were identified. All IVFs were photographed, and the images were saved. The
      areas of the IVFs and TFLs were measured with the Scion Image for Windows image
      analysis program. RESULTS: TFLs were found in 82.8% of the IVFs. The oblique
      inferior transforaminal ligament was the most common. The mean area of the IVFs
      was 155.8 +/- 51.1 mm2, and the mean area occupied by the TFLs was 46.3 +/- 37.6
      mm2. The mean percentage of the IVF area occupied by the TFLs was 28.5 +/- 18.8%.
      CONCLUSION: TFLs are common structures in the IVF and may reduce the space
      available for the spinal nerve root within the IVF. In this circumstance, any
      compromise of the IVF may impinge on the nerve root.

PMID- 15987569
TI  - Cerebral cavernous malformations associated with venous anomalies: surgical
      considerations.
AB  - OBJECTIVE: Once thought to be rare entities, mixed cerebrovascular malformations
      with pathological features of more than one type of malformation within the same
      lesion are now being recognized with increasing frequency. Their identification
      generates several hypotheses about common pathogenesis or causation-evolution
      among different types of lesions and leads to controversial discussion on
      therapeutic strategies. METHODS: Fifteen patients drawn from a consecutive series
      of 58 patients harboring cavernous malformations (25.9%) were found to have an
      associated venous malformation (VM). Three (33.3%) of the first 9 patients, in
      whom the large draining vein of the VM had been left untouched at previous
      interventions, developed recurrent and/or de novo lesions. RESULTS:
      Histopathological analysis, interestingly, revealed that the new lesions were
      different in nature (three arteriovenous angiomas in two patients, a capillary
      telangiectasia in one patient). During extirpation of the new malformation, the
      draining vein of the VM in these three patients could be coagulated without any
      adverse events. Coagulation and dissection of the draining vein of the associated
      VM was performed in six more patients of our series, and this has prevented
      development of new lesions up to now. CONCLUSION: Our results are in favor of the
      hypothesis that the draining vein of a VM is the actual underlying abnormality of
      mixed vascular malformations. Causing flow disturbances and having the potential
      for hemorrhages, the VM seems to promote the development of new adjacent
      malformations. Thus, permanent cure of associated malformations might depend on
      the surgical treatment of the VM. We present a preliminary personal series and a
      thorough review of the literature.

PMID- 15987570
TI  - Tumors of the jugular foramen: diagnosis and management.
AB  - OBJECTIVE: Jugular foramen tumors are rare cranial base lesions that present
      diagnostic and management difficulties. With the availability of new diagnostic
      procedures these tumors have been more precisely studied and questions of
      whether, when, and how these lesions should be treated often arise. Data from 106
      consecutive patients surgically treated in the past 17 years were retrospectively
      analyzed to identify surgical outcomes. METHODS: The tumors were approached by a
      multidisciplinary team composed of neurosurgeons, ear, nose, and throat surgeons,
      and neuroradiologists. Hypervascular lesions were embolized 3 to 5 days before
      surgery. The same surgical technique was used to resect all tumors. The surgical
      defect was covered with vascularized myofascial flaps. The internal carotid
      artery was infiltrated in two patients, and a saphenous graft bypass was carried
      out before removal of the lesions. The facial nerve was reconstructed with nerve
      grafts (great auricular nerve) or XII/VII anastomosis in five cases.
      Postoperative radiotherapy was carried out for malignant and invasive tumors.
      RESULTS: Paragangliomas were the most frequent lesions, followed by schwannomas
      and meningiomas. Complete excision was possible in 89% of benign tumors and 80%
      of paragangliomas. Lower cranial nerve deficit was the most frequent complication
      (10 patients, 9.4%), transient in 4 patients. Facial and cochlear nerve paralysis
      occurred in 8 patients (7.5%). The function of the facial nerve recovered
      spontaneously in 3 patients. Four patients (3.7%) developed postoperative
      cerebrospinal fluid leakage. Four patients (3.7%) died after surgery. CONCLUSION:
      Radical removal of benign jugular foramen tumors is the treatment of choice and
      may be curative. Large lesions can be radically excised in one surgical procedure
      with preservation of lower cranial nerves. Cranial base reconstruction with
      vascularized myofascial flaps reduces the incidence of postoperative
      cerebrospinal fluid leakage. Damage of the lower cranial nerves is the most
      serious surgical complication.

PMID- 15987571
TI  - Automated three-dimensional volume rendering of helical computed tomographic
      angiography for aneurysms: an advanced application of neuronavigation technology.
AB  - OBJECTIVE: To introduce the possibility of volume-rendered helical computed
      tomographic (CT) angiographic data sets by use of Medtronic StealthStation Treon
      surgical navigation technology (Medtronic Surgical Navigation Technologies,
      Louisville, CO) and to evaluate the clinical usefulness of the method in planning
      and performing surgical treatment of intracranial aneurysms. METHODS: Between
      November 2002 and July 2003, we studied 15 patients with suspected intracranial
      aneurysms. All patients but two received conventional digital subtraction
      angiography, which failed to provide the requested information. Helical CT
      angiography was performed in all patients, and data sets were transferred to the
      StealthStation system across an electronic network to be automatically
      postprocessed by use of three-dimensional (3-D) volume rendering. The 3-D volume
      rendered images were accurately analyzed to obtain more complete information
      about the aneurysm and to provide accurate treatment planning. In all patients,
      the 3-D volume-rendered model was displayed on the screen of the StealthStation
      system for the duration of the surgical procedure and compared with the
      intraoperative image. RESULTS: Data sets from CT angiography were automatically
      postprocessed by the StealthStation in seconds with excellent results, providing
      us, before and during surgery, with additional information not always available
      on traditional digital subtraction angiographic investigation. Because of the
      very short time necessary to complete this process (<5 min to obtain 3-D volume
      rendered images), it was possible to perform emergency clipping of the aneurysms
      in two patients who had been admitted in very compromised neurological
      conditions. In 12 patients, integrated digital subtraction angiography and
      automated 3-D volume-rendered images allowed an accurate presurgical evaluation.
      Furthermore, in all patients on whom surgery was performed, aneurysms were found
      in the exact location and with the same anatomic features as depicted by the 3-D
      volume-rendered models. CONCLUSION: Reports in the literature indicate that
      information gathered by CT angiography with volume rendering shows a significant
      impact on aneurysm management. The StealthStation system upgraded with the
      adequate algorithm seems to provide a time- and cost-effective method of
      performing automated 3-D volume rendering of CT angiography and provides an
      interesting alternative to the available investigation modalities in case of
      emergency.

PMID- 15987572
TI  - Localized transcranial electrical motor evoked potentials for monitoring cranial
      nerves in cranial base surgery.
AB  - OBJECTIVE: To describe a novel monitoring technique that allows "functional"
      assessment of cranial nerve continuity during cranial base surgery. METHODS:
      Facial motor evoked potentials (MEP) in 71 consecutive patients were obtained by
      localized transcranial electrical stimulation in all patients requiring facial
      nerve monitoring during the period from November 2002 to August 2004. With
      transcranial electrical stimulation localized to the contralateral cortex, facial
      nerve MEPs are obtained through stimulation of more proximal intracranial
      structures. RESULTS: Logistic regression revealed that the final-to-baseline
      facial MEP ratio predicted satisfactory (House-Brackmann Grade 1 and 2 function)
      immediate postoperative facial function (0.005 > P > 0.0005). Contingency table
      analysis showed high correlation (chi2, P < or = 2 x 10(8)) and acceptable test
      characteristics using a 50% final-to-baseline MEP ratio. CONCLUSION: Facial nerve
      MEPs recorded intraoperatively during cranial base surgery using the proposed
      technique predicts immediate postoperative facial nerve outcome. This technique
      can also be used to monitor other motor cranial nerves in cranial base surgery.

PMID- 15987573
TI  - Preserving olfactory function in anterior craniofacial surgery through cribriform
      plate osteotomy applied in selected patients.
AB  - OBJECTIVE: Olfaction is often sacrificed to gain access to the cranial base in
      anterior craniofacial surgery. We describe the long-term results of olfactory
      function in patients who underwent anterior craniofacial surgery and a cribriform
      plate osteotomy to preserve olfaction. METHODS: Between 1992 and 2004, 28
      patients underwent 29 cribriform plate osteotomies in an attempt to preserve
      olfaction during anterior craniofacial surgery performed through modified
      extended transbasal approaches. Patients' charts and office notes were reviewed
      retrospectively. Formal olfactory testing was available in 5 patients, but most
      data were based on patients' subjective reports of olfaction. Olfactory
      preservation was defined by the subjective ability to detect fumes such as
      coffee, chocolate, roses, and orange juice regardless of the intensity of the
      sensation. Follow-up was based on phone calls to patients. RESULTS: Four patients
      were lost to follow-up and excluded. Therefore, follow-up was available in 24
      patients after 25 procedures. On the basis of patients' subjective reports,
      olfaction was spared in 22 patients after 23 procedures (92%) and was confirmed
      objectively in the five patients formally tested. After surgery, only two
      patients were anosmic. CONCLUSION: Olfaction can be preserved in selected
      patients undergoing anterior craniofacial surgery. At least 1 cm of nasal mucosa
      should remain attached to the cribriform plate, which can be achieved by
      including the nasal bone in the osteotomy of the orbital bar. A medial orbital
      canthopexy is therefore necessary after these procedures.

PMID- 15987574
TI  - Functional magnetic resonance imaging in anesthetized patients: a relevant step
      toward real-time intraoperative functional neuroimaging.
AB  - OBJECTIVE: The introduction of intraoperative 1.5-T magnetic resonance imaging
      may provide up-to-date functional information in the surgical environment.
      However, feasible passive paradigms that allow the examination of anesthetized
      patients will be a precondition for intraoperative functional magnetic resonance
      imaging (fMRI). The aim of this study is to evaluate the feasibility of a
      recently developed passive fMRI paradigm for functional neuroimaging in
      anesthetized patients. METHODS: We investigated four anesthetized patients with
      intracranial pathological conditions not related to the sensorimotor cortex. All
      patients had been anesthetized with standard total intravenous anesthesia for
      more than 24 hours before the fMRI scan. Anesthesia and monitoring were sustained
      during the scanning procedure. A simultaneous electrical stimulation of the
      median and tibial nerves was applied to elicit a cortical activation using a
      custom-designed magnetoelectrically shielded conductor. Statistical evaluation
      using Statistical Parametric Mapping software (Wellcome Department of Imaging
      Neuroscience, University College, London, England) and the Talairach Daemon
      Client (Version 1.1; Research Imaging Center, University of Texas Health Science
      Center, San Antonio, TX) followed. RESULTS: Three of four patients showed a good
      activation of the sensorimotor cortex under anesthesia. In one patient, no
      significant activation was observed, presumably as a result of increased body
      impedance because of severe edema. Standard dosages of the narcotics did not
      influence the cortical response; however, stimulation intensity had to be
      increased compared with awake patients. We did not detect relevant interferences
      with magnetic resonance imaging arising from the technical setup. CONCLUSION: The
      method presented proved to be a feasible paradigm for fMRI evaluation of the
      sensorimotor cortex in anesthetized patients and thus forms a relevant step
      toward real intraoperative functional neuroimaging.

PMID- 15987575
TI  - Craniotomy for fenestration of multiloculated hydrocephalus in pediatric
      patients.
AB  - OBJECTIVE: To assess the treatment of progressive multiloculated hydrocephalus by
      craniotomy for microsurgical fenestration of cerebrospinal fluid (CSF)
      compartments to minimize the number of ventricular catheters. METHODS: We studied
      33 pediatric patients who underwent craniotomies for fenestration of progressive
      multiloculated hydrocephalus between 1989 and 2003. In 20 of 33 patients,
      hydrocephalus was attributed to intraventricular hemorrhage associated with
      prematurity. Twenty-three of 33 patients had previous central nervous system
      infections. Craniotomy was typically performed via a posterior parietal approach.
      Communication between bilateral supratentorial loculated compartments and
      posterior fossa compartments was achieved. Surgical and neurological outcomes
      were assessed. RESULTS: Fenestration of loculated CSF spaces was performed
      successfully in all patients. No new neurological deficits were noted after
      surgery, and no patients required intraoperative blood transfusions. CSF
      infections within 3 months after surgery occurred in 4 of 33 patients. Over a
      median follow-up period of 3.7 years (range, 1.5 mo to 8.7 yr), 19 of 33 patients
      required additional fenestration procedures. The number of repeat fenestration
      procedures ranged from one to six, and a total of 47 additional fenestrations
      were performed in these 19 patients. The majority of patients (n = 25) ultimately
      required shunt systems with only one ventricular catheter. The neurological
      status of these patients was extremely poor both before and after surgery. Twenty
      nine of 33 patients were severely delayed, and four were mildly delayed.
      CONCLUSION: Fenestration of multiloculated CSF compartments can enable most
      patients to function with a single ventricular catheter shunt system.
      Neurological status remains poor in this patient population.

PMID- 15987576
TI  - Intraoperative and postoperative gamma detection of somatostatin receptors in
      bone-invasive en plaque meningiomas.
AB  - OBJECTIVE: Scintigraphy with a radiolabeled somatostatin analog ((111)In
      diethylenetriaminepenta-acetic acid octreotide) detects the somatostatin
      receptors that are found in vitro in all meningiomas. Previous studies have
      proved the benefit of radioimmunoguided surgery, with a hand-held gamma probe,
      for the assessment and removal of neuroendocrine tumors. We conducted a study to
      determine whether intraoperative radiodetection of somatostatin receptors is
      feasible and could increase the probability of complete meningioma resection,
      especially for bone-invasive en plaque meningiomas, which are difficult to
      control surgically. METHODS: Eighteen patients with en plaque sphenoid wing and
      cranial convexity meningiomas were studied by preoperative and postoperative
      somatostatin receptor scintigraphy. In 10 of them, intraoperative radiodetection
      with a hand-held gamma probe was performed 24 hours after the intravenous
      administration of (111)In-diethylenetriaminepenta-acetic acid octreotide. This
      procedure was combined with a computer-aided navigation system. RESULTS: All
      preoperative scintigrams were positive. Intraoperative gamma probe detection was
      achieved for the invaded bone, dura, and periorbit of sphenoid wing meningiomas.
      The average tumor/nontumor count ratio was 2:1, with a maximum of 12:1, thus
      allowing precise detection capable of defining the tumor margins. In three cases
      of sphenoid wing meningiomas, postoperative scintigrams were helpful for the
      determination of recurrences that magnetic resonance imaging failed to detect.
      CONCLUSION: These preliminary data show that intraoperative radiodetection of
      somatostatin receptors with a hand-held gamma probe is feasible and may be
      helpful to guide the surgical removal of bone-invasive en plaque meningiomas.
      Preoperative and postoperative scintigraphy may be useful for the management and
      follow-up of patients with these tumors.

PMID- 15987577
TI  - Volumetric image guidance for motor cortex stimulation: integration of three
      dimensional cortical anatomy and functional imaging.
AB  - OBJECTIVE: Epidural electrical stimulation of the motor cortex is a promising
      treatment option in patients with intractable pain. Varying rates of success in
      long-term pain relief have been attributed to inaccurate positioning of the
      electrode array, partly because the sulcal landmarks are not directly visualized.
      We describe an integrated protocol for precise electrode placement, combining
      functional image guidance and intraoperative electrical stimulation in the awake
      patient. METHODS: Volumetric rendering of a three-dimensional (3-D) magnetic
      resonance data set was used to visualize the cortical surface and to superimpose
      functional magnetic resonance imaging data in six patients with refractory
      chronic pain. The intraoperative positioning of the quadripolar electrode array
      was monitored by functional 3-D image guidance. Continuous electrophysiological
      monitoring and clinical assessment of the motor effects complemented the
      procedure. RESULTS: Volumetrically rendered 3-D images were advantageous for the
      location of the burr hole over the perirolandic area by revealing individual
      cortical morphological features (e.g., the hand knob) and function at the same
      time. The exact position of the electrodes was verified reliably by cortical
      stimulation. No complications were observed throughout the procedures.
      CONCLUSION: The combination of 3-D functional neuronavigation, intraoperative
      electrical stimulation, and continuous motor output monitoring in awake patients
      provides optimal information for the identification of the appropriate
      somatotopic area of motor cortex. This combined imaging and stimulation approach
      for electrode positioning offers a safe and minimal invasive strategy for the
      treatment of intractable chronic pain in selected patients.

PMID- 15987578
TI  - Functional monitoring for visual pathway using real-time visual evoked potentials
      and optic-radiation tractography.
AB  - OBJECTIVE: It has been difficult to obtain anatomic and functional information
      about the visual pathway during neurosurgical operations. The aim of this study
      was to combine the information of the visual evoked potentials (VEPs) and the
      anatomic navigation of the optic radiation by diffusion tensor imaging-based
      tractography for functional monitoring of the visual pathway. METHODS: The
      subjects were two patients with brain lesions adjacent to the visual pathway.
      Diffusion tensor imaging-based tractography of the optic radiation was performed
      by selecting appropriate regions of interest and by fractional anisotropy. During
      surgery, cortical VEPs were recorded continuously under general anesthesia with
      sevoflurane. In Patient 2, the results of optic radiation tractography were
      imported to a neuronavigation system to better understand the spatial
      relationships between the lesions and the visual pathway (functional
      neuronavigation). RESULTS: In Patient 1, the lesion did not seem to be attached
      to the optic radiation, and VEP profiles remained stable during resection. In
      Patient 2, who had a lesion adjacent to the posterior horn of the lateral
      ventricle, VEPs suddenly diminished when resection reached the optic radiation as
      illustrated on the neuronavigation system. As a result, complete left hemianopia
      developed after surgery in Patient 2. CONCLUSION: We confirmed functional
      correlations of the results of diffusion tensor imaging-based tractography by
      monitoring intraoperative VEPs. The combination of continuous VEP and optic
      radiation tractography is reliable to monitor the visual function and is helpful
      in performing neurosurgical planning near the visual pathway.

PMID- 15987579
TI  - Integration of [11C]methionine-positron emission tomographic and magnetic
      resonance imaging for image-guided surgical resection of infiltrative low-grade
      brain tumors in children.
AB  - OBJECTIVE: To evaluate the interest of integrating positron emission tomography
      (PET) images with the radiolabeled tracer [(11)C]methionine (Met) into the image
      guided navigation planning of infiltrative low-grade brain tumors (LGBTs) in
      children. METHODS: Twenty-two children underwent combined Met-PET with magnetic
      resonance imaging (MRI) scans in the planning of a navigation procedure. These
      children presented an LGBT (astrocytomas, 10; oligodendrogliomas, 4; ependymomas,
      4; gangliogliomas, 4) located close to functional areas. Tumor boundaries were
      ill-defined on MRI (including T2-weighted and fluid-attenuated inversion-recovery
      scans) and could not be clearly identified for allowing a complete, or at least a
      large, image-guided resection. The PET tracer Met was chosen because of its
      higher sensitivity and specificity than MRI to detect tumor tissue. The level and
      extension of MET uptake were analyzed to define the PET contour, subsequently
      projected onto MRI scans to define a final target contour for volumetric
      resection. The quality of tumor resection was assessed by an early postoperative
      MRI and Met-PET workup. RESULTS: In 20 of the 22 children with ill-defined LGBTs,
      PET improved tumor delineation and contributed to define a final target contour
      different from that obtained with MRI alone. Met-PET guidance allowed a total
      resection of Met uptake in 17 cases that were considered total tumor resections
      because the operative margin left in place contained nontumor tissue. CONCLUSION:
      These data suggested that Met-PET guidance could help to improve the number of
      total resections and the amount of tumor removed in infiltrative LGBTs in
      children.

PMID- 15987580
TI  - In situ bypass in the management of complex intracranial aneurysms: technique
      application in 13 patients.
AB  - OBJECTIVE: Cerebral revascularization is an important part of the treatment of
      complex intracranial aneurysms that require deliberate occlusion of a parent
      artery. In situ bypass brings together intracranial donor and recipient arteries
      that lie parallel and in close proximity to one another rather than using an
      extracranial donor artery. An experience with in situ bypasses was
      retrospectively reviewed. METHODS: Thirteen aneurysms were treated with in situ
      bypasses between 1997 and 2004. During this time, 1071 aneurysms were treated
      microsurgically and 46 bypasses were performed as part of the aneurysm treatment.
      RESULTS: Treated aneurysms were located at the middle cerebral artery (MCA) in
      five patients, posteroinferior cerebellar artery (PICA) in three patients,
      vertebral artery in three patients, and anterior communicating artery in two
      patients. Seven aneurysms were fusiform or dolichoectatic, and six aneurysms were
      saccular. Microsurgical revascularization techniques included side-to-side
      anastomosis of intracranial arteries in eight patients and aneurysm excision with
      end-to-end reanastomosis of the parent artery in five patients. In situ bypasses
      included A3-A3 anterior cerebral artery bypass in two patients, anterior temporal
      artery-MCA bypass in one patient, MCA-MCA bypass in one patient, and PICA-PICA
      bypass in four patients. Aneurysm excision with arterial reanastomosis included
      three MCA aneurysms and two PICA aneurysms. On angiography, all aneurysms were
      completely obliterated and 12 bypasses were patent. CONCLUSION: In situ bypass is
      a safe and effective alternative to extracranial-intracranial bypasses and high
      flow bypasses using saphenous vein or radial artery grafts. Although in situ
      bypasses are more demanding technically, they do not require harvesting a donor
      artery, can be accomplished with one anastomosis, and are less vulnerable to
      injury or occlusion.

PMID- 15987581
TI  - Use of a novel absorbable hydrogel for augmentation of dural repair: results of a
      preliminary clinical study.
AB  - OBJECTIVE: To evaluate the safety and performance of a synthetic dural sealant as
      an adjunct to standard surgical dural repair techniques to prevent cerebrospinal
      fluid (CSF) leakage. METHODS: This study was designed as a prospective,
      nonrandomized, single-center clinical trial. The dural sealant is a synthetic
      absorbable hydrogel. Consecutive series of patients scheduled for elective
      cranial and intradural spinal surgery were included until a total of 50
      applications were achieved. It was used primarily as an adjunct to ensure
      watertight dural closure. The end point was defined as no leak with the Valsalva
      maneuver after dural sealant application. The patients were followed up for 3
      months after surgery to check for CSF leakage, standard laboratory and
      neurological examinations, and possible adverse advents. RESULTS: Of the 49
      patients, 46 were included and treated with the dural sealant because of
      spontaneous leak (n = 34; 69%) or leak after the Valsalva maneuver (n = 12; 25%).
      There was no leak in the other patients (n = 3; 6%). After application of the
      dural sealant, there was no leak in all 46 patients (100%). Of the 46 patients
      included, there was one case of overt CSF leak. One patient had a
      pseudomeningocele. There were no adverse events other than those related to the
      disease or to the surgical procedure itself. CONCLUSION: The dural sealant, a
      synthetic absorbable hydrogel, is a useful adjunct to achieve watertight dural
      closure. Application resulted in 100% closure of intraoperative CSF leaks. There
      are no evident adverse effects.

PMID- 15987582
TI  - MacCarty keyhole and inferior orbital fissure in orbitozygomatic craniotomy.
AB  - OBJECTIVE: This study had two objectives. The first was to define the ideal
      position of the MacCarty keyhole, a commonly used craniotomy entry site into
      which three of the bone cuts in orbitozygomatic craniotomy extend. The second
      objective was to examine the relationships in the inferior orbital fissure, a
      site into which two of the bone cuts in orbitozygomatic craniotomy extend.
      METHODS: Twenty frontotemporal regions from adult skulls were examined to
      delineate the relationships between the surface anatomy of the fronto
      orbitozygomatic region and the underlying frontal fossa and orbit. Drill holes
      placed along, above, and below the frontosphenoid suture were made beginning
      anteriorly at an area referred to as the three-suture junction, located at the
      junction of the frontozygomatic, sphenozygomatic, and frontosphenoid sutures. The
      site of the deep end of each hole was recorded to clarify the ideal position of
      the keyhole. The relationships in the inferior orbital fissure, the site of the
      lower end of the bone cut that begins in the orbital portion of the keyhole and
      extends along the lateral orbital wall, were also examined. CONCLUSION: Placing
      the MacCarty keyhole on the frontosphenoid suture 5 to 6 mm behind the three
      suture junction results in greater preservation of the lateral wall and roof of
      the orbit than when the hole is placed at a more anterior site, as previously
      recommended. The anterolateral part of the inferior orbital fissure, which faces
      the temporal fossa and into which the bone cuts in the orbitozygomatic craniotomy
      extend, has a lower density of vascular and neural structures than the middle and
      posteromedial parts, which are related to the infratemporal and pterygopalatine
      fossa.

PMID- 15987583
TI  - Contralateral approaches to multiple cerebral aneurysms.
AB  - Not infrequently, patients with bilateral cerebral aneurysms are encountered. In
      such patients, the ability to treat bilateral aneurysms through a unilateral
      approach spares the patient the risk and inconvenience associated with a separate
      craniotomy. The contralateral approach for aneurysm repair is technically
      feasible and safe in appropriately selected patients. Herein, we review our
      technique for maximizing contralateral exposure and clipping contralateral
      aneurysms through the four anatomic triangles that serve as corridors in this
      approach.

PMID- 15987584
TI  - Supratentorial arteriovenous malformations.
AB  - Arteriovenous malformations are a heterogeneous group of intra-axial central
      nervous system vascular lesions consisting of tangles of abnormal arteriovenous
      connections without intervening capillary beds. The heterogeneity of
      arteriovenous malformations is described by the Spetzler-Martin grading scale, a
      scale that also forms the basis for clinical decision making. The microsurgical
      treatment of appropriately selected supratentorial arteriovenous malformations is
      based on the tenets of circumferential isolation and transection of arterial
      feeders, preservation of vessels en passant and surrounding functional neural
      tissue, and skeletonization and transection of venous drainage.

PMID- 15987585
TI  - Transcranial surgery for pituitary adenomas.
AB  - Although the transsphenoidal approach is the preferred approach to the vast
      majority of pituitary tumors with or without suprasellar extension, the
      transcranial approach remains a vital part of the neurosurgical armamentarium for
      1 to 4% of these tumors. The transcranial approach is effective when resection
      becomes necessary for a portion of a pituitary macroadenoma that is judged to be
      inaccessible from the transsphenoidal route because of isolation by a narrow
      waist at the diaphragma sellae, containment within the cavernous sinus lateral to
      the carotid artery, projection anteriorly onto the planum sphenoidale, or
      projection laterally into the middle fossa. The application of a transcranial
      approach in these circumstances may still be mitigated by response to prolactin
      inhibition of prolactinomas, the frequent lack of necessity to remove
      asymptomatic nonsecretory adenomas from the cavernous sinus, and the lack of
      evidence that sustained chemical cures can be reliably achieved by removal of
      secretory adenomas (adrenocorticotropic hormone, growth hormone) from the
      cavernous sinus. Cranial base surgical techniques have refined the surgical
      approach to pituitary adenomas but have had less effect on actual surgical
      indications than anticipated. Because application of the transcranial approach to
      pituitary adenomas is and should be rare in clinical practice, it is useful to
      standardize the technique to a default mode with which the surgical team is most
      experienced and, therefore, most comfortable. Our default mode for transcranial
      pituitary surgery is the frontotemporal-orbitozygomatic approach.

PMID- 15987586
TI  - Surgical resection of intrinsic insular tumors.
AB  - This report, with an accompanying videotape, details the authors' technique for
      performing radical resections of tumors intrinsic to the insular lobe. The
      resection technique takes advantage of the fact that many intrinsic insular
      tumors grow within the confines of the insula, usually without violating pial
      borders or invading the medial structures. The method described is based on an
      anatomic dissection of the insula that uses the internal boundaries of the
      region, particularly the peri-insular sulci, as guides for resection. The
      videotape provides a visual description of this method.

PMID- 15987587
TI  - Local delivery of ibuprofen via controlled-release polymers prevents angiographic
      vasospasm in a monkey model of subarachnoid hemorrhage.
AB  - OBJECTIVE: Adhesion and migration of leukocytes into the periadventitial space
      play a role in the pathophysiology of vasospasm after subarachnoid hemorrhage
      (SAH). Intercellular adhesion molecule-1 is a determinant cell adhesion molecule
      involved in this process. Ibuprofen has been shown to inhibit intercellular
      adhesion molecule-1 upregulation and prevent vasospasm in animal models of SAH.
      In this study, we report the toxicity and efficacy of locally delivered ibuprofen
      incorporated into controlled-release polymers to prevent vasospasm in a monkey
      model of SAH. METHODS: Ibuprofen was incorporated into ethylene-vinyl acetate
      (EVAc) polymers at 45% loading (wt:wt). For the toxicity study, cynomolgus
      monkeys (n = 5) underwent surgical implantation of either blank/EVAc polymers (n
      = 3) or 45% ibuprofen/EVAc polymers (n = 2) in the subarachnoid space, were
      followed up for 13 weeks, and were killed for histopathological analysis. For the
      efficacy study, cynomolgus monkeys (n = 14) underwent cerebral angiography 7 days
      before and 7 days after surgery and SAH and were randomized to receive either a
      45% ibuprofen/EVAc polymer (n = 7; mean dose of ibuprofen, 6 mg/kg) or blank EVAc
      polymers (n = 7) in the subarachnoid space. Angiographic vasospasm was determined
      by digital image analysis. Student's t test was used for analysis. RESULTS:
      Animals implanted with ibuprofen polymers showed no signs of local or systemic
      toxicity. Animals treated with ibuprofen polymers had 91 +/- 9% lumen patency of
      the middle cerebral artery, compared with 53 +/- 11% of animals treated with
      blank/EVAc polymers (P < 0.001). CONCLUSION: Ibuprofen polymers are safe and
      prevent angiographic vasospasm after SAH in the monkey model. These findings
      support the role of cell adhesion molecules and inflammation in the
      pathophysiology of vasospasm.

PMID- 15987588
TI  - A novel minimally occlusive microvascular anastomosis technique using a temporary
      intraluminal shunt: a prospective technique to minimize brain ischemia time
      during superficial temporal artery-to-middle cerebral artery bypass.
AB  - OBJECTIVE: To describe a new technique of suturing microvessels with persistent
      perfusion via a temporary intraluminal microshunt. METHODS: Experiments were
      conducted in Wistar rats. Abdominal aorta grafts were explanted from donor rats.
      A soft silicon microcatheter was introduced into the lumen of this graft. The
      abdominal aorta of a recipient rat was prepared for end-to-side microvascular
      anastomosis. Acland clamps (S&T AG, Neuhausen, Switzerland) were applied, and a
      linear arteriotomy was made. One end of the graft-clad microcatheter was
      introduced into the lumen and occluded with a fenestrated Acland clamp. At a more
      distal part, a similar arteriotomy was performed, and the other end of the
      microcatheter was introduced into the lumen and clamped with a fenestrated Acland
      clip. This created a temporary shunt through the graft-clad microcatheter. Then,
      the graft was anastomosed to the arteriotomies at both ends, over the
      microcatheter, in an end-to-side manner. The microcatheter was explanted from the
      vessel lumen through an arteriotomy in the middle of the graft. The graft was
      clipped short to close this arteriotomy. The mean total occlusion time before
      perfusion was reestablished amounted to 3.7 minutes. This experiment was repeated
      in 12 animals (6 with and 6 without heparin) without technical complications. As
      controls, conventional anastomoses were made in 2 animals. RESULTS: Suturing
      microvessels mandates their occlusion during the period of anastomosis. Although
      ischemia is well tolerated by other tissue types, the brain is quite sensitive to
      even short windows of ischemia. Nonocclusive anastomotic techniques have been
      developed recently. These are confined to vessels with luminal diameters greater
      than 3 mm. We have evolved a novel technique that can be used with microvessels,
      as pertinent to superficial temporal artery-to-middle cerebral artery bypass.
      CONCLUSION: We have described a new technique for performing microvascular
      anastomoses over a temporary intraluminal microcatheter shunt.

PMID- 15987589
TI  - Microvascular retractor: a new concept of retracting and repositioning cerebral
      blood vessels.
AB  - OBJECTIVE: In this technical note, we report our results with a newly designed
      retractor blade that can be directly applied for the retraction and repositioning
      of cerebral blood vessels and delicate neural structures. METHODS: This new
      malleable retractor with a semicircular tip was designed to fit in the flexible
      arms of a self-retaining retractor system. After prototype evaluation and
      optimization in laboratory studies, we used the new retractor in 15 patients
      during surgical procedures that included retraction of the internal carotid
      artery during aneurysm clipping, expansion of the surgical window, and
      transposition of cranial nerves. RESULTS: No intraoperative injuries occurred to
      neurovascular structures. The retractor blade remained stable on pulsating
      vessels during the procedure and largely preserved the vessel diameter.
      CONCLUSION: The new retractor incorporates the existing advantages offered by
      flexible self-retaining retractor blades with those features that adapt to blood
      vessel retraction. Rather than concentrating force at one point as typical
      retractors do, the semicircular tip distributes the retraction force over
      multiple points along its circumference.

PMID- 15987590
TI  - New endoscope shaft for endoscopic transsphenoidal pituitary surgery.
AB  - OBJECTIVE: To describe a new endoscope shaft developed for suction-aspiration
      during endoscopic transsphenoidal pituitary surgery. METHODS: A custom-made shaft
      for a Wolf endoscope (Richard Wolf GmbH, Knittlingen, Germany) was developed with
      a height of 10 mm and a width of 5 mm, allowing an additional working channel for
      the endoscope for flexible suction tubes with a diameter of up to 10-French.
      RESULTS: The new shaft was used in 30 consecutive endoscopic transsphenoidal
      procedures for pituitary adenomas. It allowed true bimanual manipulation without
      having to fixate the endoscope. Tumor removal was facilitated, technical problems
      were not encountered, and operation time was reduced. There were no
      instrumentation-related complications. CONCLUSION: The new shaft improves the
      ergonomics of endoscopic transsphenoidal pituitary surgery in cases in which the
      endoscope is handheld.

PMID- 15987591
TI  - Revascularization of the anterior cerebral artery with an A3-A3 anastomosis and a
      superficial temporal artery bypass using an A3-radial artery graft to trap a
      giant anterior communicating artery aneurysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: How to manage the distal anterior cerebral artery (ACA)
      circulation in the treatment of a giant anterior communicating artery aneurysm or
      a giant azygous A2 aneurysm is still controversial. CLINICAL PRESENTATION: We are
      reporting the case of a 70-year-old man who presented with an evolving giant
      thrombosed anterior communicating artery aneurysm. INTERVENTION: He was
      successfully treated by trapping the aneurysm in conjunction with an A3-A3 side
      to-side anastomosis and a superficial temporal artery bypass using an A3-radial
      artery graft. The postoperative angiography showed an excellent filling of all
      the bilateral distal ACA area through the bypass. CONCLUSION: In cases in which
      direct clipping to preserve distal ACA flow is quite difficult, the bilateral ACA
      revascularization described here should be considered as another possibility.

PMID- 15987592
TI  - Sole stenting bypass for the treatment of vertebral artery aneurysms: technical
      case report.
AB  - OBJECTIVE AND IMPORTANCE: Vertebrobasilar aneurysms have a risk of rupture
      ranging from 2.5 to 50% (especially those larger than 7 mm) and a repeat bleeding
      rate of between 30 and 70%. For this reason, patients with aneurysms larger than
      7 mm should be treated. Considering the high complexity of surgical approaches in
      this area, an increasing number of reported cases are being treated with
      endovascular therapy. The purpose of this article is to determine the
      effectiveness and safety of sole stenting bypass in the treatment of three
      consecutive patients with vertebrobasilar aneurysms. CLINICAL PRESENTATION: Three
      patients (one woman and two men) with vertebrobasilar junction aneurysms were
      included in this study. Two of the patients presented with subarachnoid
      hemorrhage. INTERVENTION: An endovascular procedure was performed under general
      (two patients) or local (one patient) anesthesia and via a right femoral
      approach. By use of road map guidance, sole Express (one patient) or Express 2
      (two patients) coronary stents (Boston Scientific/Scimed, Maple Grove, MN) were
      deployed on the diseased vessel. When the stent was in place, an immediate
      partial thrombosis of the aneurysm was observed, related primarily to an intra
      aneurysmal flow pattern modification, possibly facilitated by modification of the
      angle of the parent vessel. Follow-up angiograms showed complete exclusion of the
      aneurysms within the circulation. Only one patient presented visual deficit as a
      thrombotic complication, but it disappeared completely 6 months after treatment.
      CONCLUSION: The sole stenting bypass technique seems to be a good alternative for
      the treatment of complex vertebral aneurysms by inducing thrombosis of the
      aneurysm with preservation of the parent vessel lumen.

PMID- 15987593
TI  - Treatment of a middle cerebral artery bifurcation aneurysm using a double
      neuroform stent "Y" configuration and coil embolization: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Wide-necked cerebral aneurysms have been particularly
      difficult to treat using coil embolization. The introduction of the first
      intracranial flexible stent (Neuroform stent; Boston Scientific/Target, Fremont,
      CA) has provided a great advantage to this dilemma by forming a bridge across the
      aneurysm neck and allowing the packing of coils. Despite this advancement, some
      parent vessel bifurcation aneurysms can still remain elusive to single stent and
      coiling technique. CLINICAL PRESENTATION: A 55-year-old woman presented for a
      routine follow-up angiogram. Her past history was significant for a subarachnoid
      hemorrhage and clipping of an anterior communicating aneurysm with full recovery.
      An incidental new right middle cerebral artery aneurysm was found on the
      angiogram. We report here a case of an unruptured asymptomatic wide-neck middle
      cerebral artery bifurcation aneurysm that was treated with a novel endovascular
      repair. INTERVENTION: The aneurysm was successfully treated using a double stent
      "Y" configuration and coil embolization technique using the Neuroform stent.
      Technical aspects are discussed. Perioperative management issues and potential
      pitfalls are also considered. CONCLUSION: Double stenting in "Y" configuration
      and coiling is feasible. This technique should increase the ability to
      endovascularly treat wide-necked aneurysms.

PMID- 15987594
TI  - Monorail snare technique for the recovery of stretched platinum coils: technical
      case report.
AB  - OBJECTIVE AND IMPORTANCE: Coil stretching represents a potentially hazardous
      technical complication not infrequently encountered during the embolization of
      cerebral aneurysms. Often, the stretched coil cannot be advanced into the
      aneurysm or withdrawn intact. The operator is then forced to attempt to retract
      the damaged coil, which may result in coil breakage, leaving behind a significant
      length of potentially thrombogenic stretched coil material within the parent
      vessel. To overcome this problem, we devised a technique to snare the distal,
      unstretched, intact portion of the platinum coil by use of the indwelling
      microcatheter and stretched portion of the coil as a monorail guide. CLINICAL
      PRESENTATION: We have used this technique successfully in four patients to snare
      coils stretched during cerebral aneurysm embolization. Three of these patients
      were undergoing Neuroform (Boston Scientific/Target, Fremont, CA) stent-supported
      coil embolization of unruptured aneurysms. In all cases, the snare was advanced
      easily to the targeted site for coil engagement by use of the microcatheter as a
      monorail guide. Once the intact distal segment of the coil was ensnared, coil
      removal was uneventful, with no disturbance of the remainder of the indwelling
      coil pack or Neuroform stent. TECHNIQUE: A 2-mm Amplatz Goose Neck microsnare
      (Microvena Corp., White Bear Lake, MN) was placed through a Prowler-14
      microcatheter (Cordis Corp., Miami, FL). The hub of the indwelling SL-10
      microcatheter (Boston Scientific, Natick, MA) was then cut away with a scalpel,
      leaving the coil pusher wire intact, and removed. The open 2-mm snare was then
      advanced over the outside of the coil pusher wire and microcatheter. The snare
      and Prowler-14 microcatheter were then advanced into the guiding catheter (6- or
      7-French) as a unit over the indwelling SL-10 microcatheter. By use of the SL-10
      microcatheter and coil as a "monorail" guide, the snare was advanced over and
      beyond the microcatheter and the stretched portion of the coil until the snare
      was in position to engage the distal unstretched coil. At this point, the snare
      was then closed around the intact portion of the coil, and the microcatheters,
      snare, and coil were removed as a unit. CONCLUSION: The monorail snare technique
      represents a fast, safe, and easy method by which a stretched coil can be
      removed.

PMID- 15987595
TI  - Aggressive cranial vault decompression for cranial hyperostosis: technical case
      report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Camurati-Engelmann's disease, also known as progressive
      diaphysial dysplasia, is a disorder of the bone metabolism. Neurological
      manifestations of progressive diaphysial dysplasia include cranial nerve
      dysfunction, generalized weakness, cerebellar herniation, and increased
      intracranial pressure. In the past, surgical intervention has been of limited and
      temporary benefit. We present two patients with cranial hyperostosis secondary to
      Camurati-Engelmann's disease who were treated successfully with a single surgery
      involving a combination of multiple craniotomies for cranial vault decompression.
      CLINICAL PRESENTATION: Two patients presented with signs and symptoms of
      increased intracranial pressure secondary to Camurati-Engelmann's syndrome.
      Radiological workup revealed marked cranial hyperostosis. INTERVENTION: The
      patients underwent aggressive cranial vault decompression. Multiple craniotomies
      were performed, and the inner table was then drilled down until the bone was 1 cm
      thick. CONCLUSION: Effective surgical options are needed for clinically
      significant cranial hyperostosis. In an effort to further define operative
      management in these patients, we describe a single, aggressive surgical procedure
      that may be used for successful cranial decompression.

PMID- 15987596
TI  - The expanded endonasal approach: a fully endoscopic transnasal approach and
      resection of the odontoid process: technical case report.
AB  - The transoral approach to the odontoid process is considered the "gold standard"
      for resection of extradural lesions at this location. A completely transnasal
      endoscopic approach is feasible based on anatomic studies and our experience with
      the expanded endonasal approach for neoplasms of the cranial base. An
      illustrative case is presented to demonstrate the technical details of a fully
      transnasal completely endoscopic approach for the resection of the odontoid
      process. A 73-year-old woman with a long-standing history of rheumatoid arthritis
      presented with progressive cervicomedullary compression. Complete resection of
      the odontoid was achieved with no significant morbidity. This is the first
      reported case of a completely endoscopic resection of the odontoid using a fully
      transnasal route. The report demonstrates the feasibility of this approach and
      larger clinical series with long-term follow-up will be needed to determine the
      reproducibility and validation of any potential benefits.

PMID- 15987597
TI  - Remote cerebellar hemorrhage after a spinal surgery complicated by dural tear:
      case report and literature review.
AB  - OBJECTIVE AND IMPORTANCE: This report presents a case in which cerebellar
      hemorrhage occurred after lumbar decompression surgery that was complicated by
      dural tear and prolonged cerebrospinal fluid leakage. Remote cerebellar
      hemorrhage after spinal surgery is extremely rare. Our objective is to describe
      this unusual complication, discuss the possible mechanisms of remote cerebellar
      hemorrhage, and review the literature. CLINICAL PRESENTATION: A 73-year-old woman
      underwent surgery for lumbar spinal stenosis. A dural tear occurred during
      decompression, and the patient developed remote cerebellar hemorrhage on
      postoperative Day 2. INTERVENTION: The cerebellar hemorrhage was treated
      surgically, and a biopsy of hemorrhagic brain parenchyma revealed an
      arteriovenous malformation. CONCLUSION: Although it is an extremely rare
      complication, remote cerebellar hemorrhage should be kept in mind as a possible
      complication of spinal surgery, especially in operations complicated by dural
      tears.

PMID- 15987598
TI  - Use of ultrasonic aspiration for dural opening in cranial reoperations: technical
      note.
AB  - OBJECTIVE: Dural detachment from the brain in cranial reoperations has been
      accomplished previously by selective coagulation and the cutting of brain-dural
      adhesions. The results of ultrasonic aspiration during tumor surgery or brain
      cutting procedures led the authors to speculate that the detachment of the dura
      mater from brain tumors by applying the Cavitron ultrasonic surgical aspirator
      (Valleylab, Boulder, CO [formerly Cavitron, Inc., Stamford, CT]) to the brain
      dura mater interface could be used to reduce bleeding and facilitate dural
      opening during cranial reoperations. METHODS: Ten patients underwent a second
      craniotomy for epilepsy surgery (five cases of extended temporal lobectomy and
      five cases of extended extratemporal lesionectomy). The use of ultrasonic
      aspiration and its effects on brain separation from the dura mater were examined.
      RESULTS: Intraoperative use of the Cavitron ultrasonic surgical aspirator during
      dural opening produced immediate blanching of the dura mater and enhanced
      visualization of the cortical surface without distortion of the brain anatomy.
      CONCLUSION: Incremental dural opening and brain visualization is achieved by
      careful application of ultrasonic aspiration directly into the brain-dura limit,
      producing immediate regional dural devascularization. Use of this technique
      reduces cortical and dural bleeding and enhances the ease and effectiveness of
      brain visualization.

PMID- 15987599
TI  - The host type I interferon response to viral and bacterial infections.
AB  - Type I interferons (IFN) are well studied cytokines with anti-viral and immune
      modulating functions. Type I IFNs are produced following viral infections, but
      until recently, the mechanisms of viral recognition leading to IFN production
      were largely unknown. Toll like receptors (TLRs) have emerged as key transducers
      of type I IFN during viral infections by recognizing various viral components.
      Furthermore, much progress has been made in defining the signaling pathways
      downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent
      as universally important in inducing type I IFN during infection with most
      viruses, particularly by plasmacytoid dendritic cells. New intracellular viral
      pattern recognition receptors leading to type I IFN production have been
      identified. Many bacteria can also induce the up-regulation of these cytokines.
      Interestingly, recent studies have found a detrimental effect on host cells if
      type I IFN is produced during infection with the intracellular gram-positive
      bacterial pathogen, Listeria monocytogenes. This review will discuss the recent
      advances made in defining the signaling pathways leading to type I IFN
      production.

PMID- 15987600
TI  - Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18
      expression in pulmonary epithelial cells through an interaction with cytokeratin
      18 intron 1.
AB  - The role of Ese-2, an Ets family transcription factor, in gene regulation is not
      known. In this study, the interaction between Ese-2 and cytokeratin 18 (K18)
      intron 1 was characterized in lung epithelial cells. Reporter gene assays showed
      Ese-2 was able to upregulate K18 intron 1 enhanced reporter gene expression by
      approximately 2-fold. We found that full length Ese-2 did not bind DNA strongly,
      therefore truncated versions of the protein, containing the ETS domain or Pointed
      domain, were created and tested in electrophoresis mobility shift assays.
      Multiple interactions between the ETS domain and putative DNA binding sites
      within K18 intron 1 were observed, which led to the determination of a possible
      Ese-2 DNA binding consensus sequence. These experiments suggest that Ese-2 could
      play a role in the regulation of K18 expression in lung epithelial cells.

PMID- 15987601
TI  - Expression of TRAIL and TRAIL receptors in normal and malignant tissues.
AB  - TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a member of
      the TNF family of proteins. Tumour cells were initially found to have increased
      sensitivity to TRAIL compared with normal cells, raising hopes that TRAIL would
      prove useful as an anti-tumor agent. The production of reliable monoclonal
      antibodies against TRAIL and its receptors that can stain fixed specimens will
      allow a thorough analysis of their expression on normal and malignant tissues.
      Here we report the generation of monoclonal antibodies against TRAIL and its four
      membrane-bound receptors (TR1-4), which have been used to stain a range of normal
      and malignant cells, as routinely fixed specimens. Low levels of TRAIL expression
      were found to be limited mostly to smooth muscle in lung and spleen as well as
      glial cells in the cerebellum and follicular cells in the thyroid. Expression of
      the TRAIL decoy receptors (TR3 and 4) was not as widespread as indicated by
      Northern blotting, suggesting that they may be less important for the control of
      TRAIL cytotoxicity than previously thought. TR1 and TR2 expression increases
      significantly in a number of malignant tissues, but in some common malignancies
      their expression was low, or patchy, which may limit the therapeutic role of
      TRAIL. Taken together, we have a panel of monoclonal antibodies that will allow a
      better assessment of the normal role of TRAIL and allow assessment of biopsy
      material, possibly allowing the identification of tumors that may be amenable to
      TRAIL therapy.

PMID- 15987602
TI  - Identification of eight genes that are potentially involved in tamoxifen
      sensitivity in breast cancer cells.
AB  - Although the antiestrogen agent tamoxifen has long been used to treat women with
      hormone receptor positive invasive breast carcinoma, the mechanisms of its action
      and acquired resistance to tamoxifen during treatment are largely unknown. A
      number of studies have revealed that over-activation of some signaling pathways
      can cause tamoxifen resistance; however, very little information is available
      regarding the genes whose loss-of-function alternation contribute to tamoxifen
      resistance. Here we used a forward genetic approach in vitro to generate
      tamoxifen resistant cells from the tamoxifen sensitive breast cancer cell line ZR
      75-1, and further identified the disrupted gene in different tamoxifen resistant
      clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, g
      glutamyltransferase-like activity 1, slit-robo RhoGTPase-activating protein,
      tetraspan NET-4, HSPC194, amiloride-sensitive epithelial sodium channel gene, and
      Notch2, were the eight mutated genes identified in different tamoxifen resistant
      clones, suggesting their requirement for tamoxifen sensitivity in ZR-75-1 cells.
      Since the functions of these genes are not related to each other, it suggests
      that multiple pathways can influence tamoxifen sensitivity in breast cancer
      cells.

PMID- 15987603
TI  - Characterization of transgene integration pattern in F4 hGH-transgenic common
      carp (Cyprinus carpio L.).
AB  - The integration pattern and adjacent host sequences of the inserted pMThGH
      transgene in the F4 hGH-transgenic common carp were extensively studied. Here we
      show that each F4 transgenic fish contained about 200 copies of the pMThGH
      transgene and the transgenes were integrated into the host genome generally with
      concatemers in a head-to-tail arrangement at 4-5 insertion sites. By using a
      method of plasmid rescue, four hundred copies of transgenes from two individuals
      of F4 transgenic fish, A and B, were recovered and clarified into 6 classes. All
      classes of recovered transgenes contained either complete or partial pMThGH
      sequences. The class I, which comprised 83% and 84.5% respectively of the
      recovered transgene copies from fish A and B, had maintained the original
      configuration, indicating that most transgenes were faithfully inherited during
      the four generations of reproduction. The other five classes were different from
      the original configuration in both molecular weight and restriction map,
      indicating that a few transgenes had undergone mutation, rearrangement or
      deletion during integration and germline transmission. In the five types of
      aberrant transgenes, three flanking sequences of the host genome were analyzed.
      These sequences were common carp b-actin gene, common carp DNA sequences
      homologous to mouse phosphoglycerate kinase-1 and human epidermal keratin 14,
      respectively.

PMID- 15987605
TI  - Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3
      ketoacyl-CoA reductased from developing cotton fibers.
AB  - Genes encoding enzymes involved in biosynthesis of very long chain fatty acids
      were significantly up-regulated during early cotton fiber development. Two cDNAs,
      GhKCR1 and GhKCR2 encoding putative cotton 3-ketoacyl-CoA reductases that
      catalyze the second step in fatty acid elongation, were isolated from developing
      cotton fibers. GhKCR1 and 2 contain open reading frames of 963 bp and 924 bp
      encoding proteins of 320 and 307 amino acid residues, respectively. Quantatitive
      RT-PCR analysis showed that both these genes were highly preferentially expressed
      during the cotton fiber elongation period with much lower levels recovered from
      roots, stems and leaves. GhKCR1 and 2 showed 30%-32% identity to Saccharomyces
      cerevisiae Ybr159p at the deduced amino acid level. These cotton cDNAs were
      cloned and expressed in yeast haploid ybr159wD mutant that was deficient in 3
      ketoacyl-CoA reductase activity. Wild-type growth rate was restored in ybr159wD
      cells that expressed either GhKCR1 or 2. Further analysis showed that GhKCR1 and
      2 were co-sedimented within the membranous pellet fraction after high-speed
      centrifugation, similar to the yeast endoplasmic reticulum marker ScKar2p. Both
      GhKCR(s) showed NADPH-dependent 3-ketoacyl-CoA reductase activity in an in vitro
      assay system using palmitoyl-CoA and malonyl-CoA as substrates. Our results
      suggest that GhKCR1 and 2 are functional orthologues of ScYbr159p.

PMID- 15987604
TI  - Cx31 is assembled and trafficked to cell surface by ER-Golgi pathway and degraded
      by proteasomal or lysosomal pathways.
AB  - Gap junctions, consisting of connexins, allow the exchange of small molecules
      (less than 1 KD) between adjacent cells, thus providing a mechanism for
      synchronizing the responses of groups of cells to environmental stimuli. Connexin
      31 is a member of the connexin family. Mutations on connexin 31 are associated
      with erythrokeratodermia variabilis, hearing impairment and peripheral
      neuropathy. However, the pathological mechanism for connexin 31 mutants in these
      diseases are still unknown. In this study, we analyzed the assembly, trafficking
      and metabolism of connexin 31 in HeLa cells stably expressing connexin 31.
      Calcein transfer assay showed that calcein transfer was inhibited when cells were
      treated with Brefeldin A or cytochalasin D, but not when treated with nocodazole
      or a-glycyrrhetinic acid, suggesting that Golgi apparatus and actin filaments,
      but not microtubules, are crucial to the trafficking and assembly of connexin 31,
      as well as the formation of gap junction intercellular communication by connexin
      31. Additionally, a-glycyrrhetinic acid did not effectively inhibit gap
      junctional intercellular communication formed by connexin 31. Pulse-chase assay
      revealed that connexin 31 had a half-life of about 6 h. Moreover, Western
      blotting and fluorescent staining demonstrated that in HeLa cells stably
      expressing connexin 31, the amount of connexin 31 was significantly increased
      after these cells were treated with proteasomal or lysosomal inhibitors. These
      findings indicate that connexin 31 was rapidly renewed, and possibly degraded by
      both proteasomal and lysosomal pathways.

PMID- 15987606
TI  - Identification, characteristic and phylogenetic analysis of type II DNA
      topoisomerase gene in Giardia lamblia.
AB  - The genes encoding type II DNA topoisomerases were investigated in Giardia
      lamblia genome, and a type IIA gene, GlTop 2 was identified. It is a single copy
      gene with a 4476 bp long ORF without intron. The deduced amino acid sequence
      shows strong homology to eukaryotic DNA Top 2. However, some distortions were
      found, such as six insertions in the ATPase domain and the central domain, a
      approximately 100 aa longer central domain; a approximately 200 aa shorter C
      terminal domain containing rich charged residues. These features revealed by
      comparing with Top 2 of the host, human, might be helpful in exploiting drug
      selectivity for antigiardial therapy. Phylogenetic analysis of eukaryotic enzymes
      showed that kinetoplastids, plants, fungi, and animals were monophyletic groups,
      and the animal and fungi lineages shared a more recent common ancestor than
      either did with the plant lineage; microsporidia grouped with fungi. However,
      unlike many previous phylogenetic analyses, the "amitochondriate"G. lamblia was
      not the earliest branch but diverged after mitochondriate kinetoplastids in our
      trees. Both the finding of typical eukaryotic type IIA topoisomerase and the
      phylogenetic analysis suggest G. lamblia is not possibly as primitive as was
      regarded before and might diverge after the acquisition of mitochondria. This is
      consistent with the recent discovery of mitochondrial remnant organelles in G.
      lamblia.

PMID- 15987608
TI  - Levodopa and the progression of Parkinson's disease.

PMID- 15987607
TI  - Hippocampal function, declarative memory, and schizophrenia: anatomic and
      functional neuroimaging considerations.

PMID- 15987609
TI  - Rivastigmine for dementia associated with Parkinson's disease.

PMID- 15987611
TI  - The non-motor symptom complex of Parkinson's disease: a comprehensive assessment
      is essential.
AB  - Parkinson's disease (PD) is a progressive disease that usually affects the motor
      system but is also associated with a non-motor symptom (NMS) complex that ranges
      from dribbling saliva, constipation, depression, sleep disorders, apathy,
      hallucinations, and dementia. These features contribute significantly to
      morbidity and institutionalization, more than quadrupling the cost of care.
      Furthermore, recent evidence suggests that NMS such as constipation, olfaction,
      rapid eye movement behavior disorder, fatigue, and depression may be markers of a
      preclinical stage of PD. PD-NMS are not well recognized in clinical practice and
      part of the reason is the lack of any instrument that aims to assess the complex
      range of NMS of PD in a unified and integrated manner. Recently, an
      international, multidisciplinary PD-NMS group has developed an integrated
      questionnaire and scale to assess NMS of PD in a comprehensive manner. This will
      help improve care and treatment of PD in the future.

PMID- 15987610
TI  - Restless legs syndrome.
AB  - Restless legs syndrome is a very common and still under-diagnosed neurologic
      condition that can cause severe morbidity. The pathology centers around central
      nervous system iron homeostatic dysregulation with subsequent alterations in
      dopaminergic functioning. Genetic studies will hopefully soon identify specific
      abnormalities. Treatment of restless legs syndrome with dopaminergic medications
      is highly effective, although augmentation may occur eventually and require
      dosing flexibility.

PMID- 15987613
TI  - Sleep disturbances in epilepsy patients.

PMID- 15987614
TI  - Functional magnetic resonance imaging in the treatment of epilepsy.
AB  - Although structural magnetic resonance imaging (MRI) is now in routine use in the
      evaluation and management of epilepsy, functional MRI (fMRI) has recently begun
      to provide a noninvasive and widely available modality for assessing regional
      brain function. fMRI studies of language and memory are able to show discrete
      areas of activation in cerebral cortex, are useful in lateralizing language and
      memory during presurgical evaluation, and are providing further insight into the
      processes underlying cerebral plasticity in the brains of epilepsy patients. The
      use of fMRI for localization of ictal phenomena may also contribute to the
      localization of seizure foci and to a better understanding of the pathophysiology
      of electrographic spikes. The combination of fMRI with electroencephalogram and
      other advanced structural imaging techniques may not only improve seizure
      localization, but may also contribute valuable information towards a better
      understanding of the pathophysiology of epilepsy and its consequences on brain
      development.

PMID- 15987615
TI  - Genetics of drug resistance in epilepsy.
AB  - Drug resistance is a major clinical problem in epilepsy, affecting one in three
      patients. It is likely to have a complex multifactorial basis, with environmental
      and genetic contributions. Knowledge of robust genetic factors underlying drug
      resistance might both improve prediction and permit the development of novel
      rational treatments for resistance. A number of genetic association studies have
      been undertaken examining the effect of a range of candidate genes for
      resistance. Although some of these candidates have good biologic motivation for
      mediating resistance, currently there are no common genetic variants proven to
      generate the common clinical phenomenon of resistance. Much work remains to be
      done, but the scene is set for exciting developments that will hold therapeutic
      potential for patients with drug-resistant epilepsy.

PMID- 15987612
TI  - Movement disorder emergencies.
AB  - For the past 4 years, Dr. Stanley Fahn and I have given a course at the American
      Academy of Neurology annual meeting on the topic of movement disorder
      emergencies. The purpose of this review article is to summarize the topic and to
      present it to readers of this journal. The text of this article has appeared in
      nearly the same form as the Academy syllabus accompanying our course. It is being
      presented here so that readers of the journal may review the material.

PMID- 15987616
TI  - Continuous electroencephalogram monitoring in critically ill patients.
AB  - The past few years have witnessed remarkable advances in continuous EEG
      monitoring (cEEG). The indications and applications for cEEG are broadening,
      including detection of nonconvulsive seizures, spell characterization, and
      prognostication. Seizures are common in the critically ill, are usually
      nonconvulsive, and can easily be missed without cEEG. Interpretation and clinical
      management of the complex periodic and rhythmic EEG patterns commonly identified
      in these patients require further study. With the use of quantitative analysis
      techniques, cEEG can detect cerebral ischemia very early, before permanent
      neuronal injury occurs. This article reviews the indications and recent advances
      in cEEG in critically ill patients. Continuous brain monitoring with cEEG is
      rapidly becoming the standard of care in critically ill patients with neurologic
      impairment.

PMID- 15987617
TI  - The use of monotherapy in patients with epilepsy: an appraisal of the new
      antiepileptic drugs.
AB  - The use of antiepileptic drugs (AEDs) in monotherapy is always preferred to a
      polytherapy regimen because monotherapy facilitates drug compliance, is
      associated with a lower risk of toxicity, and is less costly. In addition, the
      yield of polytherapy to render a patient seizure-free when monotherapy regimens
      did not is relatively low. The available data derived from randomized controlled
      trials suggest that standard and new AEDs appear to display comparable
      antiepileptic efficacy but they differ with respect to tolerability and toxicity,
      which may be related to their pharmacodynamic and pharmacokinetic properties. New
      AEDs appear to be better tolerated than standard AEDs and to have fewer
      pharmacokinetic interactions than standard AEDs. In this article, we review the
      advantages of using AEDs in monotherapy in patients with newly diagnosed and
      refractory epilepsies, focusing on the individual properties of the drugs that
      may make them more appropriate in various patient groups.

PMID- 15987619
TI  - Facilitated percutaneous coronary intervention: is this strategy ready for
      implementation?
AB  - Reperfusion therapy with pharmacologic fibrinolysis has provided striking
      reductions in mortality following acute ST-elevation myocardial infarction
      (STEMI). Nevertheless, the limitations of fibrinolysis are well recognized.
      Attempts to improve reperfusion with bolus-only fibrinolysis, and combination
      regimens including enoxaparin and glycoprotein IIb/IIIa inhibition have not led
      to improvements in mortality. Although both prehospital fibrinolysis and primary
      percutaneous coronary intervention (PCI) have reduced mortality, these strategies
      are associated with considerable logistic constraints, hampering widespread
      implementation. Potentially, a hybrid strategy combining the speed and simplicity
      of pharmacologic reperfusion with the ability to ensure epicardial vessel
      patency, and providing definitive management of the culprit lesion remains an
      attractive option. Facilitated PCI for STEMI may extend the benefit of myocardial
      reperfusion to a greater number of patients. The true benefit of this strategy
      will be defined by ongoing large-scale clinical trials. If results are positive,
      the clinical practice determinants required for the effective application of this
      strategy to the wider clinical community will need careful consideration.

PMID- 15987620
TI  - Resistance to antiplatelet therapy.
AB  - Cardiovascular mortality continues to be high and events continue to occur in
      patients taking antiplatelet medications. Aspirin and clopidogrel have become
      integral parts of management in patients with coronary artery disease and after
      percutaneous angioplasty. However, the platelet responses to aspirin and
      clopidogrel are not uniform. Diminished or lack of response to these agents has
      been termed aspirin resistance and clopidogrel resistance. These phenomena have
      tremendous clinical significance as together they may occur in more than 50% of
      all patients on chronic therapy with aspirin or clopidogrel. Postulated
      mechanisms of aspirin and clopidogrel resistance include alterations in genetic,
      pharmacokinetic, and platelet properties. There is a dearth of information in
      regard to their clinical significance, methods to test them, and strategies to
      treat them. Further research is necessary in these areas to identify these
      patients and treat them appropriately.

PMID- 15987621
TI  - Acute coronary syndromes in black Americans: is treatment different? Should it
      be?
AB  - Black Americans with acute coronary syndromes (ACS) are at greater risk and have
      poorer outcomes than white Americans. The reasons for this appears, at least in
      part, to be due to a greater burden of baseline risk factors, longer delays prior
      to seeking medical care, and underutilization of aggressive treatment strategies
      in high-risk individuals. A guiding principle of treatment of ACS is that
      patients at highest risk should receive the most immediate and aggressive
      therapy. However, compared with whites, blacks with ACS paradoxically receive
      less aggressive medical therapy, and are less often referred for cardiac
      catheterization, percutaneous coronary interventions, and bypass surgery.
      Treatment is--but should not be--different in black Americans. Changing this and
      improving care for ACS in blacks requires better strategies for decreasing
      patient delays, earlier recognition and diagnosis of ACS, and more effective
      implementation of evidence-based treatment guidelines.

PMID- 15987622
TI  - Direct thrombin inhibitors.
AB  - Direct thrombin inhibitors (DTIs) are a new class of therapeutics possessing
      theoretic advantages over unfractionated heparin (UFH). In contrast to UFH, DTIs
      do not activate platelets, have no circulating inhibitors, and bind to both free
      and clot-bound thrombin. These theoretical advantages have spurred clinical
      trials investigating DTIs in a variety of cardiovascular indications. Currently,
      the major role for DTIs in cardiology is as an adjunct during percutaneous
      coronary intervention (PCI). Such a role stems from the results of the Randomized
      Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2
      randomized trial, in which bivalirudin with provisional abciximab was
      demonstrated to be equivalent to UFH plus planned abciximab with respect to
      ischemic endpoints, while being associated with less bleeding. Ongoing clinical
      trials will define the role of bivalirudin as an adjunct to primary PCI for ST
      segment elevation myocardial infarction and in non-ST segment elevation acute
      coronary syndrome as an adjunct to an early invasive strategy.

PMID- 15987624
TI  - Issues with care in the elderly patient presenting with acute ischemia.
AB  - The issues surrounding care of the elderly patient with acute coronary syndromes
      (ACS) present significant challenges to clinicians and investigators. The elderly
      often have atypical symptoms of acute ischemia, have greater medical
      comorbidities, and are more likely to die from ischemic heart disease. Important
      differences exist among elderly patients with ACS as compared with their younger
      counterparts, including age-related changes in physiology, metabolism of drugs,
      and overall functional status, all of which influence treatment patterns and
      clinical outcomes. Given the absence of elderly patients in many clinical trials,
      these high-risk individuals are sometimes managed with more conservative
      strategies, which at times diverge from accepted guidelines. This review
      addresses clinically important issues in the care of elderly patients with acute
      ischemia and highlights recent studies that provide new insight into this complex
      area of cardiovascular care.

PMID- 15987623
TI  - Using biomarkers to assess risk and consider treatment strategies in non-ST
      segment elevation acute coronary syndromes.
AB  - Since the first biomarker of myocardial necrosis was described in 1954, cardiac
      specific biomarkers have been increasingly identified. This, coupled with
      dramatic evolution in assay technology and resultant highly sensitive assays, has
      rendered a remarkable transformation in the medical use of biomarkers. Initially
      used to aid in diagnosis of myocardial infarction, newer biomarkers of
      inflammation, plaque instability, and ischemia may complement biomarkers of
      necrosis by providing tools to diagnose impending myocardial necrosis before
      irreversible damage occurs, and offering additional information for risk
      stratification. Importantly, biomarkers of different processes may be combined to
      enhance risk stratification above that of any single marker.

PMID- 15987625
TI  - Heart failure and shock complicating acute coronary syndromes.
AB  - Heart failure (HF) complicating acute coronary syndromes (ACS) is a heterogeneous
      clinical syndrome characterized by varying degrees of pulmonary congestion, and
      in its severest form, by profound organ hypoperfusion (cardiogenic shock). The
      occurrence of HF in patients with ACS has long been recognized as a strong
      predictor of increased morbidity and mortality. As such, there is increased
      interest in better understanding the epidemiology and management of this common
      clinical syndrome. This manuscript reviews recent insights from work in this
      area, including recent important trials evaluating the impact of renin
      angiotensin system inhibition, early beta-blockade, and aggressive reperfusion
      strategies.

PMID- 15987626
TI  - How aggressive should lipid lowering be among patients with acute coronary
      syndromes?
AB  - Results from recent clinical trials have advanced our understanding of the role
      of HMG-CoA reductase inhibitors (statins) in the management of patients following
      acute coronary syndrome (ACS) episodes. In aggregate, these trials have
      demonstrated the safety and efficacy associated with initiation of intensive
      statin therapy prior to hospital discharge following an ACS episode, independent
      of baseline low-density lipoprotein (LDL) cholesterol concentrations. Based on
      the results of these trials, there is now compelling evidence to support
      intensive lipid lowering with high-dose statins initiated prior to hospital
      discharge for all patients suffering ACS episodes with a target for LDL
      cholesterol of 70 mg/dL or lower, recommendations that have been incorporated
      into clinical practice guideline recommendations in the most recent position
      statement from the National Cholesterol Education Panel.

PMID- 15987627
TI  - Clinical presentations of unoperated and operated adults with congenital heart
      disease.
AB  - The clinical presentation of adults with congenital heart disease (ACHD) is
      exceptionally diverse. Operated, unoperated acyanotic, and cyanotic patients
      often have similar physiologic characteristics, and thus shared clinical
      symptomatology. Five illustrative cases are included to highlight important
      considerations in the diagnosis and management of ACHD. This article focuses on
      epidemiology, natural history, clinical outcomes, and use of ancillary studies in
      commonly encountered cardiac defects.

PMID- 15987628
TI  - Transposition of the great arteries: long-term outcome and current management.
AB  - There is a large group of young adults who survived atrial baffle repair of
      transposition of the great arteries. Most survivors are asymptomatic, although
      nearly all have decreased exercise capacity. Loss of sinus rhythm and atrial
      arrhythmias are common and increase with age. There is concern about the ability
      of the right ventricle to function long term as a systemic pump, and recent
      publications have highlighted right ventricular dysfunction in this patient
      population. Sudden death and congestive heart failure are the main causes of
      death, and outcomes beyond 30 years are unknown. Pulmonary artery banding, late
      arterial switch, and cardiac transplantation are employed when intractable
      arrhythmias or right ventricular failure threaten survival or quality of life.

PMID- 15987629
TI  - Pregnancy in women with congenital heart disease.
AB  - Congenital heart disease is the most common form of structural heart disease
      affecting women of childbearing age in developed countries. Pregnancy in these
      patients is associated with an increased risk to both mother and fetus.
      Appropriate prepregnancy evaluation and counseling is recommended to assess the
      pregnancy-related maternal and fetal risk and to identify patients who should
      avoid pregnancy. Once pregnancy occurs, cardiovascular reevaluation is generally
      recommended; the frequency is individualized. Monitoring during delivery may be
      necessary and the postpartum period is a concern in select individuals. Data
      regarding the outcome of pregnancy in patients with operated congenital cardiac
      defects are available. Individualized care is mandatory.

PMID- 15987630
TI  - A full house: complications from an uncorrected patent ductus arteriosus.
AB  - True aneurysms of the pulmonary artery are rare, and are most often due to
      pulmonary hypertension arising from congenital heart defects. We report the case
      of a 40-year-old man with an uncorrected patent ductus arteriosus who presented
      with pulmonary infarction and pneumonia, and subsequently died of cardiac arrest.
      Autopsy revealed a large pulmonary artery aneurysm, in situ pulmonary artery
      thrombosis complicated by pulmonary infarction, pulmonary artery dissection, and
      cardiac tamponade. Although each of these complications is rare in and of itself,
      this case demonstrates the entire spectrum of complications from a single
      uncorrected congenital cardiac anomaly.

PMID- 15987631
TI  - MK-801 and dextromethorphan block microglial activation and protect against
      methamphetamine-induced neurotoxicity.
AB  - Methamphetamine causes long-term toxicity to dopamine nerve endings of the
      striatum. Evidence is emerging that microglia can contribute to the neuronal
      damage associated with disease, injury, or inflammation, but their role in
      methamphetamine-induced neurotoxicity has received relatively little attention.
      Lipopolysaccharide (LPS) and the neurotoxic HIV Tat protein, which cause dopamine
      neuronal toxicity after direct infusion into brain, cause activation of cultured
      mouse microglial cells as evidenced by increased expression of intracellular
      cyclooxygenase-2 and elevated secretion of tumor necrosis factor-alpha. MK-801, a
      non-competitive NMDA receptor antagonist that is known to protect against
      methamphetamine neurotoxicity, prevents microglial activation by LPS and HIV Tat.
      Dextromethorphan, an antitussive agent with NMDA receptor blocking properties,
      also prevents microglial activation. In vivo, MK-801 and dextromethorphan reduce
      methamphetamine-induced activation of microglia in striatum and they protect
      dopamine nerve endings against drug-induced nerve terminal damage. The present
      results indicate that the ability of MK-801 and dextromethorphan to protect
      against methamphetamine neurotoxicity is related to their common property as
      blockers of microglial activation.

PMID- 15987632
TI  - Genome-wide analysis of sex-enriched gene expression during C. elegans larval
      development.
AB  - Sex determination in C. elegans is controlled by the TRA-1 zinc finger protein, a
      Ci/GLI homolog that promotes female cell fates throughout the body. The
      regulatory hierarchy that controls TRA-1 is well established, but the downstream
      effectors that establish sexual dimorphism during larval development remain
      largely unknown. Here, we describe the use of cDNA microarrays to identify sex
      enriched transcripts expressed during three stages of C. elegans larval
      development. By excluding previously identified germline-enriched transcripts, we
      focused on somatic sexual development. This approach identified a large number of
      sex-enriched transcripts that are good candidates to encode regulators of somatic
      sexual development. We found little overlap between genes with sex-enriched
      expression in early versus late larval development, indicating that distinct
      sexual regulatory programs operate at these times. Genes with sex-enriched
      expression are found throughout the genome, with no strong bias between autosomes
      and X chromosomes. Reporter gene analysis revealed that these genes are expressed
      in highly specific patterns in a variety of sexually dimorphic cells. We searched
      for TRA-1 consensus DNA binding sites near genes with sex-enriched expression,
      and found that most strongly sex-enriched mRNAs are likely to be regulated
      indirectly by TRA-1. These results suggest that TRA-1 controls sexual dimorphism
      through a small number of intermediary regulators rather than by acting directly
      on the full constellation of genes involved in sex-specific differentiation.

PMID- 15987633
TI  - Aspirin inhibits NF-kappaB activation in a glycolysis-depleted lung epithelial
      cell line.
AB  - Inhibition of glycolysis at the phosphofructo-1-kinase step slows cell growth.
      For this reason, overexpression of fructose-2,6-bisphosphatase is a potential
      target for antineoplasic treatments. However, therapeutic objectives may be
      compromised by side effects of glycolysis restriction, including enhanced
      resistance to oxidants and tumor necrosis factor-alpha (TNF-alpha), as well as
      increased activity of the nuclear factor kappa B (NF-kappaB). In this study we
      evaluated aspirin as an adjuvant drug for glycolysis restriction by
      overexpression of fructose-2,6-bisphosphatase. The effect of aspirin on
      antioxidant defences and NF-kappaB activity were evaluated both in control cells
      and in fructose-2,6-bisphosphatase-overexpressing cells. Interestingly, aspirin
      induced inhibition of NF-kappaB activity was greater in transfectants with
      restricted glycolysis than in control cells. Our results indicate that aspirin is
      a suitable complement to therapy based on glycolysis restriction to overcome
      resistance associated with increased NF-kappaB activity and oxidative stress.

PMID- 15987635
TI  - The effects of curcumin on depressive-like behaviors in mice.
AB  - Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese
      medicinal formula, which has been used effectively to treat depression-related
      diseases in China. There is no information available about the antidepressant
      activity of curcumin, the active component of curcuma longa. In the present
      study, we analyzed the effects of curcumin on depressive-like behaviors in mice,
      using two animal models of depression. Our results showed that curcumin treatment
      at 5 and 10 mg/kg (p.o.) significantly reduced the duration of immobility in both
      the tail suspension and forced swimming tests. These doses that affected the
      immobile response did not affect locomotor activity. In addition, the
      neurochemical assays showed that curcumin produced a marked increase of serotonin
      and noradrenaline levels at 10 mg/kg in both the frontal cortex and hippocampus.
      Dopamine levels were also increased in the frontal cortex and the striatum.
      Moreover, curcumin was found to inhibit monoamine oxidase activity in the mouse
      brain. These findings suggest that the antidepressant-like effects of curcumin
      may involve the central monoaminergic neurotransmitter systems.

PMID- 15987634
TI  - Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte
      differentiation.
AB  - We investigated the effects of anandamide on peroxisome proliferator-activated
      receptor gamma (PPARgamma) activity. In two different transactivation systems
      using either full-length or only the ligand binding domain of PPARgamma, we
      showed that anandamide, but not palmitoylethanolamide induced transcriptional
      activation of PPARgamma in a dose dependent manner with an EC50 of 8 microM. In
      addition, competition binding experiments showed that anandamide but not
      palmitoylethanolamide binds directly to PPAR-ligand binding domain. We also found
      that anandamide treatment induced 3T3-L1 fibroblast differentiation into
      adipocytes. Indeed, anandamide induced triglyceride droplet accumulation and the
      expression of PPARgamma responsive genes such as CCAAT enhancer binding protein
      alpha (C-EBPalpha), aP2, PerilipinA and Acrp30. Furthermore, the PPARgamma
      antagonist (GW9662) inhibited the anandamide-induced 3T3-L1 differentiation
      confirming that this is a PPARgamma-mediated process. Altogether, these data
      indicate that anandamide binds PPARgamma and induces cellular PPARgamma
      signaling.

PMID- 15987636
TI  - Transfer of beta subunit regulation from high to low voltage-gated Ca2+ channels.
AB  - High voltage-activated Ca(2+) channel expression and gating is controlled by
      their beta subunits. Although the sites of interaction are known at the atomic
      level, how beta modulates gating remains to be determined. Using a chimeric
      approach, beta subunit regulation was conferred to a low voltage-activated
      channel. Regulation was dependent on a rigid linker connecting the alpha(1)
      interaction domain to IS6. Chimeric channels also revealed a role for IS6 in
      channel gating. Taken together, these results support a direct coupling model
      where beta subunits alter movements in IS6 that occur as the channel transits
      between closed, open, and inactivated states.

PMID- 15987637
TI  - Arabidopsis ubiquitin-specific protease 6 (AtUBP6) interacts with calmodulin.
AB  - Calmodulin (CaM), a key Ca(2+) sensor in eukaryotes, regulates diverse cellular
      processes by interacting with many proteins. To identify Ca(2+)/CaM-mediated
      signaling components, we screened an Arabidopsis expression library with
      horseradish peroxidase-conjugated Arabidopsis calmodulin2 (AtCaM2) and isolated a
      homolog of the UBP6 deubiquitinating enzyme family (AtUBP6) containing a Ca(2+)
      dependent CaM-binding domain (CaMBD). The CaM-binding activity of the AtUBP6
      CaMBD was confirmed by CaM mobility shift assay, phosphodiesterase competition
      assay and site-directed mutagenesis. Furthermore, expression of AtUBP6 restored
      canavanine resistance to the Deltaubp6 yeast mutant. This is the first
      demonstration that Ca(2+) signaling via CaM is involved in ubiquitin-mediated
      protein degradation and/or stabilization in plants.

PMID- 15987638
TI  - Parkin interacts with the proteasome subunit alpha4.
AB  - Mutations in the parkin gene encoding an E3 ligase are responsible for autosomal
      recessive Parkinson's disease. Putative parkin substrates and interacting
      partners have been identified, but the molecular mechanism underlying parkin
      related neurodegeneration is still unclear. We have identified the 20S
      proteasomal subunit alpha4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a
      new interacting partner of parkin. The C-terminal IBR-RING domain of parkin and
      the C-terminal part of alpha4 were essential for the interaction. Biochemical
      studies revealed that alpha4 was not a substrate for parkin-dependent
      ubiquitylation. Putative functions of the interaction might therefore be
      substrate presentation to the proteasome or regulation of proteasomal activity.
      Full-length parkin and parkin lacking the N-terminal ubiquitin-like domain
      slightly increased the proteasomal activity in HEK 293T cells, in line with the
      latter hypothesis.

PMID- 15987639
TI  - Sphingosine-1-phosphate induces a PDGFR-dependent cell detachment via inhibiting
      beta1 integrin in HEK293 cells.
AB  - Several different types of interactions between sphingosine-1-phosphate (S1P)
      receptors and platelet-derived growth factor receptor (PDGFR) have been revealed
      recently. In this work, we used HEK293 cells to further investigate the potential
      crosstalk. Interestingly, we observed that S1P specifically induced a PDGFR
      dependent cell detachment in HEK293 cells, which could be inhibited by AG1296, a
      specific inhibitor for PDGFR. EGFR on the other hand, did not have any effect on
      cell detachment. The detachment was extracellular matrix (ECM) protein specific,
      suggesting the involvement of specific integrin molecules. When beta(1) integrin
      was engaged into an active state, S1P-induced cell detachment was blocked,
      suggesting that S1P induced an inside-out inhibitory effect on beta(1) integrin.
      G(i) protein and ERK activation were required for the cell detachment induced by
      S1P, suggesting an endogenous receptor for S1P is likely to be involved.

PMID- 15987640
TI  - Spark-induced agglomeration of aqueous polymeric suspensions.
AB  - Discharging a high-energy spark underwater creates a shock wave that dissipates
      through an acoustic field. Colloidal acrylate polymers suspended in water
      containing dissolved calcium are agglomerated as a result. The degree of
      agglomeration increases with the number of sparks applied and with increasing
      calcium content. The calcium decreases the charge on the colloidal particles and
      thereby increases their propensity to be agglomerated by the acoustic wave. These
      observations are confirmed in full-scale trials in paper recycling mills where
      sparking improves the efficiency of centrifugal cleaners by increasing the
      particle size of the contaminants.

PMID- 15987641
TI  - Thermodynamically stable dispersions induced by depletion interactions.
AB  - When small particles are added to a colloidal dispersion of large particles, a
      depletion interaction between large particles occurs because the small ones are
      depleted from the gaps between the former particles. In the present paper, a cell
      model is employed to examine the behavior of a dispersion of large particles
      immersed in an electrolyte solution containing small particles. In this model,
      each cell consists of one large particle in its center and an associated
      atmosphere. Double-layer, van der Waals, and depletion interactions, as well as
      entropic effects, have been taken into account. When the change of the free
      energy with respect to that of the electrolyte solution is negative (and this
      happens in most cases), the dispersions of large particles are stable from a
      thermodynamic point of view. With increasing volume fraction of the small
      particles, the free energy change becomes more negative. The formation of gels
      observed experimentally in concentrated emulsions is explained through the
      formation of a thermodynamically stable dispersion.

PMID- 15987642
TI  - A quantitative high-throughput chemotaxis assay using bioluminescent reporter
      cells.
AB  - Here we report on a novel biophotonic assay system for the detection and
      quantitation of chemotaxis, the directed movement of cells in response to
      chemokine concentration gradients. Our assay employs a firefly luciferase (ffLuc)
      generated biophotonic signal to quantify cellular migration in 96-well microplate
      chemotaxis instruments. When compared to direct cell enumeration, the biophotonic
      reporter method is superior in accuracy, reproducibility, and sensitivity. As a
      proof-of-concept, we demonstrate the utility of this assay for quantifying the
      chemotactic response of ex vivo expanded ffLuc(+) primary human T-cells to
      recombinant human chemokines MCP-1, RANTES, and IP-10. The 96-well microplate
      format and in situ biophotonic detection of cells are amenable to high-throughput
      screening of peptides and small molecule libraries to identify agonists and
      antagonists of cellular chemotaxis, to analyze biological fluids for chemotactic
      activity, and to study chemotaxis in a variety of cell types.

PMID- 15987643
TI  - Expression of matrix metalloproteinase-26 (MMP-26) mRNA in mouse uterus during
      the estrous cycle and early pregnancy.
AB  - Matrix metalloproteinases (MMPs) and their tissue inhibitors play important roles
      in the remodeling of extracellular matrix (ECM). MMP-26, also called endometase
      or matrilysin-2, is a novel member of the MMP family. The present study was to
      investigate the temporal and spatial expression of MMP-26 mRNA in mouse uterus
      during the estrous cycle and early pregnancy by using in situ hybridization and
      semi-quantitative RT-PCR. In this study, MMP-26 mRNA was found to be localized to
      the luminal and glandular epithelium at proestrus and estrus, and the expression
      level was decreased significantly from metestrus to dioestrus. During pre
      implantation period, MMP-26 mRNA was predominantly expressed in luminal and
      glandular epithelium at much higher level; whereas it switched to stroma during
      peri-implantation period, and also appeared in the blastocysts and the
      implantation sites. The results suggested that MMP-26 might play a role in the
      cycling changes of mouse uterus during the estrous cycle and embryo implantation.

PMID- 15987644
TI  - Biomonitoring in occupational health: scientific, socio-ethical, and regulatory
      issues.
AB  - Biomonitoring is one of the best available tools for the prevention of
      deleterious effects resulting from occupational exposure to chemicals. The
      availability of analytical techniques having low detection limits allows for the
      measurement of numerous biomarkers. Complemented with quality control programs,
      our ability to collect validated information on exposure to toxicants improves.
      This is important as exposure doses tend to decrease in workplaces. Concurrently,
      there is an increasing preoccupation towards skin exposure, which cannot
      currently be reliably assessed through external measurements. Furthermore, as
      lower exposure doses are encountered, background concentrations of some
      biomarkers become a serious limitation to their use. This prompts researchers to
      seek for minor, more specific metabolites, that may however be produced through
      metabolic pathways that are prone to larger inter-individual variations.
      Assessment of exposure to complex mixtures of chemicals is another major
      challenge. There is a growing interest towards ethical issues in biomonitoring.
      The understanding of the advantages and of the limits of this preventive approach
      may be very different among occupational health professionals, but more
      importantly, between health professionals and those they are seeking to protect,
      i.e., the workers themselves. Many organizations have proposed guideline values
      for biomarker concentrations, but these seldom find their way in the various
      countries' bylaws. One underlying reason might be the greater complexity of the
      scientific aspects of biomarkers, whose understanding is required to set limit
      values, compared to the process of setting airborne limit concentrations. But the
      fact that the latter does not consider all aspects of biological complexity does
      not make it more reliable.

PMID- 15987645
TI  - Novel extrahepatic cytochrome P450s.
AB  - The cytochrome P450 enzymes are highly expressed in the liver and are involved in
      the metabolism of xenobiotics. Because of the initiatives associated with the
      Human Genome Project, a great progress has recently been seen in the
      identification and characterization of novel extrahepatic P450s, including
      CYP2S1, CYP2R1, CYP2U1 and CYP2W1. Like the hepatic enzymes, these P450s may play
      a role in the tissue-specific metabolism of foreign compounds, but they may also
      have important endogenous functions. CYP2S1 has been shown to metabolize all
      trans retinoic acid and CYP2R1 is a major vitamin D 25-hydroxylase. Regarding
      their metabolism of xenobiotics, much remains to be established, but CYP2S1
      metabolizes naphthalene and it is likely that these P450s are responsible for
      metabolic activation of several different kinds of xenobiotic chemicals and
      contribute to extrahepatic toxicity and carcinogenesis.

PMID- 15987646
TI  - Ethical and practical issues regarding research in children: the European
      perspective.
AB  - Children, like all humans, are exposed to compounds in the environment and
      sometimes to drugs. The effect of this exposure cannot simply be deducted from
      studies in adults or animals. Effects might be different and even more dramatic
      than in adults due to the stage of growth and development of the infant. Around
      80% of drugs used in young individuals are not licensed for use in this age
      group. Almost three new chemical compounds enter the environment each day.
      Toxicological studies in infants and children therefore are needed and ethically
      acceptable. However, appropriate safeguards must be taken into account. According
      to the Good Clinical Practice Directive of the European Parliament (2001/20) not
      only therapeutic, but also non-therapeutic research in infants and children is
      allowed, provided the study can only be conducted in children, and the results of
      the study in children will be of benefit to the group represented and no more
      than minimal harm and risk is inflicted to the children. Many more toxicological
      studies are needed in children and infants. Not conducting these studies is
      detrimental for this age group.

PMID- 15987647
TI  - Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm
      Chromatin Structure Assay (SCSA).
AB  - Studies over the past two decades have clearly shown that reproductive toxicants
      cause sperm DNA fragmentation. This DNA fragmentation can usually be detected
      prior to observing alterations of metaphase chromosomes in embryos. Thus, Sperm
      Chromatin Structure Assay (SCSA)-detected DNA damage is viewed as the molecular
      precursor to later gross chromosome damage observed under the light microscope.
      SCSA measurements of animal or human sperm consist of first obtaining a fresh or
      flash frozen neat semen sample in LN2 or dry ice. Samples are then sent to a SCSA
      diagnostic laboratory where the samples are thawed, diluted to approximately 1-2
      x 106 sperm/ml, treated for 30 s with a pH 1.2 detergent buffer and then stained
      with acridine orange (AO). The low pH partially denatures DNA at the sites of DNA
      strand breaks and the AO-ssDNA fluoresces red while the AO-dsDNA fluoresces
      green. Flow cytometry measurements of 5000 sperm/sample provide statistically
      robust data on the ratio of red to green sperm, the extent of the DNA
      fragmentation and the standard deviations of measures. Numerous experiments on
      rodents treated with reproductive toxicants clearly showed that SCSA measures are
      highly dose responsive and have a very low CV. Different agents that act on germ
      cells at various stages of development usually showed sperm DNA fragmentation
      when that germ cell fraction arrived in the epididymis or ejaculate. Some of
      these treated samples were capable of successful in vitro fertilization but with
      frequent embryo failure. A 2-year longitudinal study of men living a valley town
      with a reported abnormal level of infertility and spontaneous miscarriages and
      also a seasonal atmospheric smog pollution, showed, for the first time, that SCSA
      measurements of human sperm DNA fragmentation were detectable and correlated with
      dosage of air pollution while the classical semen measures were not correlated.
      Also, young men spraying pesticides without protective gear are at an increased
      risk for elevated sperm DNA fragmentation. Extensive DNA fragmentation probably
      cannot be repaired by the egg and the spontaneous abortion rate is approximately
      2x higher if a man has more than 30% of sperm showing DNA fragmentation. DNA
      fragmentation is an excellent marker for exposure to potential reproductive
      toxicants and a diagnostic/prognostic tool for potential male infertility.

PMID- 15987648
TI  - Neuroprotective properties of nitric oxide and S-nitrosoglutathione.
AB  - Oxidative stress and apoptosis may play an important role in the
      neurodegeneration. The present paper outlines antioxidative and antiapototic
      mechanisms of nitric oxide and S-nitrosothiols, which could mediate
      neuroprotection. Nitric oxide generated by nitric oxide synthase or released from
      an endogenous S-nitrosothiol, S-nitrosoglutathione may up-regulate antioxidative
      thioredoxin system and antiapototic Bcl-2 protein through a cGMP-dependent
      mechanism. Moreover, nitric oxide radicals have been shown to have direct
      antioxidant effect through their reaction with free radicals and iron-oxygen
      complexes. In addition to serving as a stabilizer and carrier of nitric oxide, S
      nitrosoglutathione may have protective effect through transnitrosylation
      reactions. Based on these new findings, a hypothesis arises that the homeostasis
      of nitric oxide, S-nitrosothiols, glutathione, and thioredoxin systems is
      important for protection against oxidative stress, apoptosis, and related
      neurodegenerative disorders.

PMID- 15987649
TI  - Trouble shooting in toxicopathology.
AB  - Toxicopathology, also referred to as toxicologic pathology, can be defined as the
      study of structural and functional changes in cells, tissues, and organs that are
      induced by toxicants (such as drugs, industrial and agricultural chemicals),
      toxins (chemicals of biological origin such as mycotoxins and phycotoxins), and
      physical agents (such as heat and radiation); the investigation of the mechanisms
      by which these changes are induced; and the development of risk assessment and
      risk management policies based on such information. Toxicologic pathology
      primarily deals with the morphologic or structural effects of the toxicant and
      the mechanism by which this structural effect is induced. This article highlights
      some of the problems that toxicologic pathologists may encounter in obtaining and
      interpreting pathology lesions. By alerting toxicologists to some of these
      issues, it is hoped that a better understanding of the use and limitations of
      toxicologic pathology data will occur.

PMID- 15987650
TI  - Natural controlled HIV infection: preserved HIV-specific immunity despite
      undetectable replication competent virus.
AB  - Long-term non-progressive HIV infection, characterized by low but detectable
      viral load and stable CD4 counts in the absence of antiviral therapy, is observed
      in about 5% of HIV-infected patients. Here we identified four therapy naive
      individuals who are strongly seropositive for HIV-1 but who lack evidence of
      detectable HIV p24 antigen, plasma RNA, and proviral DNA in routine diagnostic
      testing. With an ultrasensitive PCR, we established that frequencies of pol
      proviral DNA sequences were as low as 0.2-0.5 copies/10(6) PBMC. HIV could not be
      isolated using up to 30x10(6) patient PBMC. One individual was heterozygous for
      CCR5 Delta32, but CCR5 expression on CD4+ T cells was normal to high in all four
      individuals. In vitro R5 and X4 HIV-1 susceptibility of CD8-depleted PBMC of all
      study subjects was significantly lower than the susceptibility of CD8-depleted
      PBMC of healthy blood donors. All individuals expressed protective HLA-B*58s
      alleles and showed evidence of HIV-specific cellular immunity either by staining
      with HLA-B*57 tetramers folded with an HIV RT or gag peptide or after stimulation
      with HIV-1 p24 gag, RT, or nef peptides in ELIspot analysis. HIV-specific CD4+ T
      helper cells were demonstrated by proliferation of CD4+ T cells and intracellular
      staining for IL-2 and IFNgamma after stimulation with an HIV-gag peptide pool.
      Sera of all individuals showed antibody-mediated neutralization of both R5 and X4
      HIV-1 variants. These data implicate that very low-level antigen exposure is
      sufficient for sustained HIV-specific immunity and suggest the possibility of a
      multi-factorial control of HIV infection.

PMID- 15987651
TI  - Degradation and metabolism of hexazinone by two isolated bacterial strains from
      soil.
AB  - Two hexazinone-degrading bacterial strains were isolated from soil by enrichment
      culture technique, and identified as Pseudomonas sp. and Enterobacter cloacap.
      The two purified isolates, designated as WFX-1 and WFX-2, could rapidly degrade
      hexazinone with a half-life of 3.08 days and 2.95 days in mineral salt medium
      (MSM), while their mixed bacterial culture was found to degrade hexazinone, at an
      initial concentration of 50 microg/ml, by enhancing 2.3-fold over that when the
      isolates were used alone. Two microbial metabolites (A and D) were obtained by
      preparative TLC and identified on the basis of the spectral data of IR, 1H NMR
      and HPLC-ESI-MS, but both of them were known products as they had been reported
      in soil and vegetation metabolites of hexazinone. However, metabolites B and C
      were new degradates, whose molecular weights (MW) were 157 and 156, respectively,
      being reported from microbial metabolism for the first time.

PMID- 15987652
TI  - Transient effect of the herbicide flazasulfuron on carbohydrate physiology in
      Vitis vinifera L.
AB  - In the Champagne vineyard, most of the areas treated in early 2000 with the newly
      approved herbicide flazasulfuron had vines with altered growth and yellow leaves
      throughout the growing season. In order to clarify the physiological
      perturbations caused on the non-target grapevine and their potential
      consequences, C nutrition of grape plants grown in vineyards treated or not with
      flazasulfuron in 2000 was characterized during the following season. Vines from
      treated areas exhibited yellow leaves and an alteration of photosynthetic
      activity, characterized by declines in leaf gas exchanges (by 85%) and
      photosynthetic pigment concentrations (by 88%), and a marked disorganization of
      the leaf plastids. The herbicide also caused a decrease in leaf starch and
      soluble carbohydrate levels (-74% and -90%, respectively). Surprisingly, some
      vines re-greened after bloom, then exhibiting similar carbohydrate physiology to
      those grown in a non-treated area. Thus, recovery of CO(2) fixation rates,
      plastid ultra-structure, pigment concentrations and carbohydrate levels was found
      in re-greening leaves. Unlike the informations available in the literature, our
      results showed that flazasulfuron may be phytotoxic for grapevine. However, this
      toxicity was overcome the following year, indicating that vines have the
      potential to recover from this herbicide stress after one season.

PMID- 15987653
TI  - Zinc tolerance and accumulation in Pteris vittata L. and its potential for
      phytoremediation of Zn- and As-contaminated soil.
AB  - A field investigation and pot experiments were conducted to determine the
      potential of arsenic (As) hyperaccumulator, Pteris vittata L., to remediate sites
      co-contaminated with zinc (Zn) and As. We found that P. vittata L. had a very
      high tolerance to Zn and grew normally at sites with high Zn concentrations. In
      addition, P. vittata L. could effectively take up Zn into its fronds, with a
      maximum of 737 mg kg(-1) under field conditions. In pot experiments, the
      accumulated Zn concentration increased significantly as the Zn treatment was
      raised from 0 to 2000 mg kg(-1), with a maximum Zn accumulation of 0.22 mg pot(
      1). Although the concentration of As in P. vittata L. was reduced by the addition
      of Zn, total frond accumulation of As was elevated when the Zn treatment was
      increased from 0 to 1000 mg kg(-1), with a maximum As accumulation of 8.3 mg pot(
      1) in the presence of 1000 mg kg(-1) Zn. The high Zn tolerance, relatively high
      ability to accumulate Zn, and great capacity to accumulate As under conditions of
      suppression by high Zn suggest that P. vittata L. could be useful for the
      remediation of sites co-contaminated with Zn and As.

PMID- 15987654
TI  - Seasonal variations in natural organic matter and its impact on coagulation in
      water treatment.
AB  - In the past decade, a number of UK and US water utilities have been experiencing
      operational difficulties connected with the increased dissolved organic carbon
      (DOC) levels during the autumn and winter periods. This has been observed as an
      increase in the production of disinfection-by-products (DBP), and a greater
      coagulant demand. Resin adsorption techniques were used to fractionate raw water
      and investigate the variation in surface charge and coagulant-humic interactions
      over a 36-month period. A change in the natural organic matter (NOM) composition
      throughout the year was observed, with the fulvic acid fraction (FAF) increasing
      from 36% in September to 61% in November. However, a reduction in treatment
      performance is not simply due to an increase in DOC concentrations (from 4.3 to
      14.5 mg L-1), but also a change in the charge density of the NOM. It was found
      that hydrophilic NOM fractions possess negligible charge density (<0.06 meq g
      1DOC), and it is the hydrophobic NOM fractions, FAF in particular, that exert the
      greater dominance on coagulation control. The hydrophilic NOM fractions are less
      amenable to removal through conventional coagulation with metal salts, and are
      therefore likely to indicate the DOC residual remaining after treatment.
      Understanding the seasonal changes in NOM composition and character and their
      reactivity with coagulants should lead to a better optimisation of the
      coagulation process and a more consistent water quality.

PMID- 15987655
TI  - simBio: a Java package for the development of detailed cell models.
AB  - Quantitative dynamic computer models, which integrate a variety of molecular
      functions into a cell model, provide a powerful tool to create and test working
      hypotheses. We have developed a new modeling tool, the simBio package (freely
      available from ), which can be used for constructing cell models, such as cardiac
      cells (the Kyoto model from Matsuoka et al., 2003, 2004 a, b, the LRd model from
      Faber and Rudy, 2000, and the Noble 98 model from Noble et al., 1998), epithelial
      cells (Strieter et al., 1990) and pancreatic beta cells (Magnus and Keizer,
      1998). The simBio package is written in Java, uses XML and can solve ordinary
      differential equations. In an attempt to mimic biological functional structures,
      a cell model is, in simBio, composed of independent functional modules called
      Reactors, such as ion channels and the sarcoplasmic reticulum, and dynamic
      variables called Nodes, such as ion concentrations. The interactions between
      Reactors and Nodes are described by the graph theory and the resulting graph
      represents a blueprint of an intricate cellular system. Reactors are prepared in
      a hierarchical order, in analogy to the biological classification. Each Reactor
      can be composed or improved independently, and can easily be reused for different
      models. This way of building models, through the combination of various modules,
      is enabled through the use of object-oriented programming concepts. Thus, simBio
      is a straightforward system for the creation of a variety of cell models on a
      common database of functional modules.

PMID- 15987656
TI  - 'Ca(2+)-induced Ca(2+) entry' or how the L-type Ca(2+) channel remodels its own
      signalling pathway in cardiac cells.
AB  - The adjustment of Ca(2+) entry in cardiac cells is critical to the generation of
      the force necessary for the myocardium to meet the physiological needs of the
      body. In this review, we present the concept that Ca(2+) can promote its own
      entry through Ca(2+) channels by different mechanisms. We refer to it under the
      general term of 'Ca(2+)-induced Ca(2+) entry' (CICE). We review short-term
      mechanisms (usually termed facilitation) that involve a stimulating effect of
      Ca(2+) on the L-type Ca(2+) current (I(Ca-L)) amplitude (positive staircase) or a
      lessening of Ca(2+)-dependent inactivation of I(Ca-L). This latter effect is
      related to the amount of Ca(2+) released by ryanodine receptors (RyR2) of the
      sarcoplasmic reticulum (SR). Both effects are involved in the control of action
      potential (AP) duration. We also describe a long-term mechanism based on Ca(2+)
      dependent down-regulation of the Kv4.2 gene controlling functional expression of
      the repolarizing transient outward K(+) current (I(to)) and, thereby, AP
      duration. This mechanism, which might occur very early during the onset of
      hypertrophy, enhances Ca(2+) entry by maintaining Ca(2+) channel activation
      during prolonged AP. Both Ca(2+)-dependent facilitation and Ca(2+)-dependent down
      regulation of I(to) expression favour AP prolongation and, thereby, promote
      sustained voltage-gated Ca(2+) entry used to enhance excitation-contraction (EC)
      coupling (with no change in the density of Ca(2+) channels per se). These self
      maintaining mechanisms of Ca(2+) entry have significant functions in remodelling
      Ca(2+) signalling during the cardiac AP. They might support a prominent role of
      Ca(2+) channels in the establishment and progression of abnormal Ca(2+)
      signalling during cardiac hypertrophy and congestive heart failure.

PMID- 15987657
TI  - Stage I squamous cell carcinoma of vagina complicating pregnancy: successful
      conservative treatment.
AB  - BACKGROUND: Vaginal squamous cell carcinoma in pregnancy is very rare situation.
      CASE: The patient was a 33-year-old woman, presenting with a complaint of vaginal
      brownish discharge at a 23 weeks of gestation. On pelvic examination at that
      time, a 2 by 2 cm mass on posterior vaginal fornix was seen. Biopsy of the lesion
      demonstrated a nonkeratinizing type invasive squamous cell carcinoma. She desired
      to continue the pregnancy and postpone the treatment until after delivery. On 23
      weeks of gestation, we performed wide local excision, confirming T1 stage. On 33
      weeks of gestation, a pelvic lymphadenectomy was carried out at the time of
      cesarean section to secure lymph node status pathologically. Further, she began
      intracavitary brachytherapy via vaginal cylinder in an adjuvant setting. She is
      36 months from her initial surgery and remains disease free. CONCLUSION:
      Treatment could be individualized for primary stage I vaginal squamous cell
      carcinoma complicating pregnancy.

PMID- 15987658
TI  - Developmental expression of clock genes in the Syrian hamster.
AB  - Transcription/translation feedback loops consisting of multiple clock genes are
      thought to be essential for circadian oscillations at cellular, tissue and
      organismal levels. We examined the developmental expressions of three clock genes
      (Bmal1, Cry1 and Per1) in the Syrian hamster to probe the oscillatory properties
      of the suprachiasmatic nucleus (SCN) over the first 4 days after the completion
      of SCN neurogenesis. Samples were taken at the dam's circadian times 6, 12, and
      18 daily over 4 days in constant dim light and processed for in situ
      hybridization using 35S-labeled RNA probes. Collection times were based on the
      phases of Bmal1 and Per1 rhythms in adult SCN and on an observed difference in
      Per1 mRNA at CT6 and 18 on postnatal day 2. For the developmental study, sections
      from each brain were processed in parallel for the three genes. Bmal1 was
      prominently expressed in the fetal SCN while Per1 and Cry1 were only weakly
      expressed. Transcripts of all three genes showed higher abundance just after
      birth. At subsequent ages, Bmal1 showed a significant decrease, while Per1
      continued to be greater than prenatal levels. Significant variation was detected
      across circadian times for Cry1, but no circadian variation was detected for Per1
      and Bmal1. Molecular oscillations equivalent to those observed in adults were not
      present in the fetal SCN despite evidence for an entrainable pacemaker at that
      time. An absence of robust oscillations during early SCN development may in part
      explain the strong phase-setting effects of pharmacological agents on the
      fetal/neonatal clock.

PMID- 15987659
TI  - A 10-min method for preparation of highly electrocompetent Pseudomonas aeruginosa
      cells: application for DNA fragment transfer between chromosomes and plasmid
      transformation.
AB  - A rapid microcentrifuge-based method is described for preparation of Pseudomonas
      aeruginosa electrocompetent cells with up to 10,000-fold increased transformation
      efficiencies over existing procedures. This increased efficiency now enables the
      use of transformation for all applications requiring DNA transfer. These include
      transfer of chromosomal mutations marked with antibiotic resistance genes between
      P. aeruginosa strains, which solves the riddle of not having an efficient and
      reliable transduction procedure for this bacterium. Not surprisingly, the method
      also allows for very efficient transformation with replicative plasmids, with
      transformation efficiencies ranging from 10(7) to >10(11) transformants per
      microgram of DNA. Lastly, with efficiencies of up to >10(3) transformants per
      microgram of DNA the method replaces in most instances conjugation for the
      transfer of non-replicative plasmids used in gene replacement, site-specific gene
      integration and transposon mutagenesis experiments.

PMID- 15987660
TI  - RNA-conjugated template-switching RT-PCR method for generating an Escherichia
      coli cDNA library for small RNAs.
AB  - The cDNA conversion of RNA molecules is a prerequisite for their analysis. In the
      case of prokaryotic RNAs, cDNA conversion is difficult due to a lack of the long
      poly(A) tails that are found in eukaryotic mRNAs. The full cDNAs for eukaryotic
      mRNAs can be amplified by the reverse transcription polymerase chain reaction (RT
      PCR) using the template-switching method together with an oligo(dT) primer. To
      amplify the full cDNAs for prokaryotic RNAs, we modified the template-switching
      RT-PCR method by adopting an RNA linker at the 3' end of the target RNAs. Using
      this method, which we named as RNA-conjugated template-switching RT-PCR (RC/TS RT
      PCR), we constructed a cDNA library for small RNAs from cold-shock-treated
      Escherichia coli cells. To confirm that the cDNAs were amplified by RC/TS RT-PCR
      without a loss of sequence information, clones carrying the 6S RNA sequence were
      analyzed from the cDNA library for small RNAs ranging from 130 to 350 nt. We
      found that the 6S RNA sequences were fully converted into the corresponding
      cDNAs, confirming that RC/TS RT-PCR is a useful method for constructing a cDNA
      library for small RNAs in E. coli. This method can be also used to construct a
      cDNA library for non-poly(A)-containing RNAs from eukaryotic cells.

PMID- 15987661
TI  - Interactions of GRF(1-29)NH2 with plasma proteins and their effects on the
      release of the peptide from a PLAGA matrix.
AB  - The administration of the GRF(1-29)NH2 Growth Hormone Releasing Hormone analog is
      known as relevant of the concept of drug delivery system using a bioresorbable
      matrix. However, the release of this peptide from poly(dl-lactic acid-co-glycolic
      acid) matrices is affected by its insolubility at neutral in salted media and in
      plasma as well. In order to investigate the origin and the nature of the
      insolubility in these media in more details, the precipitates collected when the
      peptide was set in contact with saline, isotonic pH=7.4 phosphate buffer and
      plasma were analyzed by various techniques, namely weighting, gel chromatography,
      1D- and 2D-immunoelectrophoresis, and dialysis to discern the soluble from the
      insoluble or aggregated fractions. It is shown that precipitation in protein-free
      salted media is due to a salting out phenomenon complemented by the
      neutralization of the solubilizing electrostatic charges in the isotonic buffer.
      In contrast, the precipitation in plasma is due to inter polyelectrolyte-type
      complexation that involved polyanionic proteins having a rather low isoelectric
      point like albumin, transferin, haptoglobulin and IgG immunoglobulins. When a
      rather large quantity of GRF(1-29)NH2 was entrapped in bioresorbable pellets
      working at a percolating regime after subcutaneous implantation in rats, the
      peptide was slowly released despite the complexation with plasma proteins.
      However only a very small part of the peptide was found in blood, this small part
      being still large enough to cause a detectable increase of the circulating growth
      hormone concentration. Attempts made to increase the solubility of the peptide in
      plasma were successful when the peptide was combined with arginine, an amino acid
      known to promote the poor hormonal activity of injected GRF(1-29)NH2 solutions
      under clinical conditions.

PMID- 15987662
TI  - The Palliative Care in Assisted Living (PCAL) pilot study: successes, shortfalls,
      and methodological implications.
AB  - Troubling deficits exist in palliative care (PC) of older adults under the
      prevailing "terminal care"-oriented model. We previously described a PC model-
      TLC--that provides a blueprint for remedying these shortfalls. In this model, PC
      is envisioned as Timely and Team-oriented, Longitudinal, and Collaborative and
      Comprehensive. We present results of the Palliative Care in Assisted Living
      pilot, comparing two TLC model-based, facility delivered interventions for
      improving the PC of elderly assisted living residents in Sacramento, California,
      a growing and under-researched population. The less intensive intervention
      involved one assessment followed by a PC improvement recommendation letter to the
      resident, family member, primary provider, and facility staff, while the more
      intensive intervention involved assessments and letters every three months.
      Primary outcomes were SF-36 Physical (PCS) and Mental (MCS) Component scores and
      recommendation adherence. Eighty-one subjects enrolled (mean age 85), 58 in the
      more and 23 in the less intensive group. A loved one attended 56% of baseline
      assessments. Most subjects expressed a preference for maintaining current quality
      of life over prolonging life at reduced quality. None were eligible for hospice
      care. A total of 418 recommendations (mean 5.1 per subject) were generated
      concerning symptoms, mood, functional impairments, and advance directives. We
      found no significant differences in recommendation adherence between more (42%)
      and less (44%) intensive groups, and no significant changes in PCS and MCS scores
      within or between groups. However, a loved one's attendance of the baseline
      assessment was associated with improved PCS scores (p=0.04). Our pilot study had
      methodological limitations that could account for the lack of significant outcome
      effects. In this context, and given the myriad unmet PC needs we detected,
      interventions based on the TLC model might allow delivery of timely PC to
      assisted living residents not eligible for hospice care. Further studies
      exploring the TLC model appear warranted.

PMID- 15987663
TI  - A new microperoxidase from Marinobacter hydrocarbonoclasticus.
AB  - The preparation and characterization of a new microperoxidase obtained from
      proteinase K-treated cytochrome c(552) from Marinobacter hydrocarbonoclasticus
      (previously known as Pseudomonas nautica) are presented. This microperoxidase
      (MMP-5) has novel structural properties relative to previously reported
      microperoxidases, as the two intervening amino acid (X) residues within the
      consensual CXXCH c-type heme binding motif are missing, yielding a heme
      pentapeptide with increased solubility in aqueous solvents and a 1-2 order of
      magnitude higher stability of the monomeric state relative to canonical
      microperoxidases. The electronic spectra in the near-UV and visible regions have
      been studied as a function of MMP-5 concentration and pH. The spectroscopic
      properties of MMP-5 are typical of microperoxidases with high-spin hexa- or
      pentacoordinate heme species dominant in the 1-8 pH range and low-spin states
      prevailing at higher pH values. In the presence of hydrogen peroxide, MMP-5
      displays peroxidatic activities towards several compounds.

PMID- 15987664
TI  - Systematic variation in effects of serotonin and norepinephrine on repetitive
      firing properties of ventral horn neurons.
AB  - Spinal interneurons are essential integrators of descending and peripheral input
      that receive profuse monoaminergic influence from brainstem nuclei. In this
      study, the effects of the monoamines serotonin and norepinephrine on the
      intrinsic properties of ventral horn interneurons were investigated in a slice
      preparation of the lumbar cord of 7-19 day old rats. Three cell groups with
      distinct firing patterns in response to steps of injected current were observed
      and classified as repetitive-firing, initial-burst or single-spiking. Input
      conductance tended to be largest in single-spiking cells whereas repetitive
      firing cells showed the greatest tendency for spontaneous firing and had the
      fastest rate of rise for the action potential. Rhythmic firing behaviors were
      defined by the frequency-current relation evoked by linearly increasing current
      ramps. The monoaminergic modulation of firing patterns and frequency-current
      relations was primarily studied in repetitive-firing cells. The frequency-current
      threshold current was decreased in cells with high pre-drug values and increased
      in cells with low pre-drug values. Therefore, monoamine administration decreased
      the input-output heterogeneity of the repetitive-firing cells by compressing the
      range of frequency-current threshold currents. This action of monoamines may have
      a key role in the suppression of sensory-evoked reflexes and the production of
      coordinated movement.

PMID- 15987665
TI  - Control of oro-facio-lingual movements by the substantia nigra pars reticulata:
      high-frequency electrical microstimulation and GABA microinjection findings in
      rats.
AB  - To provide direct evidence for substantia nigra pars reticulata (SNr) control of
      oro-facio-lingual muscle activity, high-frequency electrical microstimulation
      (mainly trains of 20, 333-Hz cathodal pulses at 40-60 microA) and GABA
      microinjection (1-5 microl of 10 mM GABA in saline) were carried out using a
      three-barreled microelectrode at the same SNr site in lightly anesthetized,
      chronically decorticated rats (n=39). Decortication eliminated the possibility
      that SNr microstimulation might activate corticofugal fibers descending in the
      adjoining cerebral peduncle. When the most ventral layer of the SNr was
      approached, high-amplitude electromyographic (EMG) activity of up to 6 mV with a
      distinctive waveform appeared synchronously with electrical stimuli in the
      anterior digastric, masseter, genioglossus, and levator labii superioris muscles.
      This EMG activity was evoked bilaterally, with an ipsilateral predominance. Eye
      movements, mostly rotation of the eyeball vertically down in the orbit, were
      noted. Infrequent blinking was also noted. Histologic examination localized the
      effector site to the middle third of the mediolateral extent of the caudal SNr
      corresponding to between 5.8 mm (level of the oculomotor nerve) and 6.5mm (caudal
      end of the SNr) caudal to bregma; and to the ventralmost peripeduncular region of
      the SNr corresponding to 7.7 mm to 8.0 mm beneath the cortical surface. We
      referred to this site as the substantia nigra pars reticulata oro-facio-lingual
      (SNr-ofl) region. GABA injection produced tonic EMG discharge with consistent
      amplitude in all of the four muscles studied. The GABA effect was negated by a
      preceding microinjection of the GABA-A receptor antagonist bicuculline, whereas
      saline control injection had no effect. Changes in amplitude of evoked EMG
      activity according to location of the stimulating microelectrode reflected
      somatotopic organization of the SNr-ofl region. This extremely localized
      electrical and receptor microstimulation in the SNr produced synchronized
      powerful contraction of jaw, tongue, and facial muscles with different neural
      innervation. These findings advance our understanding of the mechanisms of the
      SNr concerning oro-facio-lingual movements.

PMID- 15987666
TI  - Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell.
AB  - Most drugs of abuse increase dopamine (DA) in the nucleus accumbens (NAc), and do
      so every time as a pharmacological response. Palatable food also releases
      accumbens-shell DA, but in naive rats the effect can wane during a long meal and
      disappears with repetition. Under select dietary circumstances, sugar can have
      effects similar to a drug of abuse. Rats show signs of DA sensitization and
      opioid dependence when given intermittent access to sucrose, such as alterations
      in DA and mu-opioid receptors, cross-sensitization with amphetamine and alcohol,
      and behavioral and neurochemical signs of naloxone-precipitated withdrawal. The
      present experiment asks whether sucrose-dependent rats release DA each time they
      binge. We also predict that acetylcholine (ACh), which rises as the end of a
      meal, will be delayed in rats with intermittent access to sucrose. To create
      dependency, the experimental group (Daily Intermittent Sucrose) was maintained on
      a diet of 12-h food deprivation that extended 4 h into the dark, followed by 12-h
      access to a 10% sucrose solution and chow, daily, for 21 days. As the main
      result, these rats gradually increased their sucrose intake from 37 to 112 ml per
      day (from 13 to 20 ml in the first hour of access), and repeatedly increased
      extracellular DA to 130% of baseline as measured in the NAc shell by
      microdialysis during the first hour of sucrose access on day 1, day 2 and day 21.
      Three control groups failed to show a significant increase in extracellular DA on
      day 21: Sucrose only for 1 h on days 1 and 21 (Sucrose Twice), ad libitum access
      to sucrose and chow (Daily Ad libitum Sucrose), and intermittent chow instead of
      sucrose (Daily Intermittent Chow). Acetylcholine measured at the same time as DA,
      increased significantly toward the end and after each test meal in all groups. In
      the Daily Intermittent Sucrose group, the highest ACh levels (133%) occurred
      during the first sample after the sucrose meal ended. In summary, sucrose
      dependent animals have a delayed ACh satiation response, drink more sucrose, and
      release more DA than sucrose- or binge-experienced, but non-dependent animals.
      These results suggest another neurochemical similarity between intermittent
      bingeing on sucrose and drugs of abuse: both can repeatedly increase
      extracellular DA in the NAc shell.

PMID- 15987667
TI  - Testosterone modulates Ca(v2.2) calcium channels' functional expression at rat
      levator ani neuromuscular junction.
AB  - Spinal nucleus of bulbocavernosus and its target musculature, the bulbocavernosus
      and levator ani muscles, are sexually dimorphic, and their sexual differentiation
      depends on plasmatic levels of testosterone. Electrophysiological and
      immunocytochemical studies have demonstrated that at mammalian adult
      neuromuscular junctions only P/Q-type Ca2+ channels (Ca(v2.1)), mediate evoked
      transmitter release. Here we report that N-type Ca2+ channel (Ca(v2.2)) blocker
      omega-Conotoxin GVIA, as well as Ca(v2.1) blocker omega-Agatoxin IVA,
      significantly reduced quantal content of transmitter release by approximately 80%
      and approximately 70% respectively at levator ani muscle of the adult rats,
      indicating that neuromuscular transmission is jointly mediated by both types of
      channels. In these synapses, we also observed that castration and restitution of
      plasmatic testosterone in rats resulted in changes in the sensitivity to omega
      Conotoxin GVIA. Castration induced, whereas testosterone treatment avoided,
      functional loss of Ca(v2.2), as mediators of transmitter release in these
      synapses. Strikingly, the expression and localization of alpha1B subunits, which
      form the pore of the Ca(v2.2) channel, were similar at control, gonadectomized
      and gonadectomized testosterone-treated rats, suggesting that testosterone may
      regulate the coupling mechanisms between Ca(v2.2) and transmitter release at the
      neuromuscular junctions of these sexually dimorphic motoneurons.

PMID- 15987668
TI  - Genetic characterization of the mitochondrial DNA from Lepeophtheirus salmonis
      (Crustacea; Copepoda). A new gene organization revealed.
AB  - The mitochondrial DNA (mtDNA) from the salmon louse, Lepeophtheirus salmonis, is
      15445 bp. It includes the genes coding for cytochrome B (Cyt B), ATPase subunit 6
      and 8 (A6 and A8), NADH dehydrogenase subunits 1-6 and 4L (ND1, ND2, ND3, ND4,
      ND4L, ND5 and ND6), cytochrome c oxidase subunits I-III (COI, COII and COIII),
      two rRNA genes (12S rRNA and 16S rRNA) and 22 tRNAs. Two copies of tRNA-Lys are
      present in the mtDNA of L. salmonis, while tRNA-Cys was not identified. Both DNA
      strands contain coding regions in the salmon louse, in contrast to the other
      copepod characterized Tigriopus japonicus, but only a few genes overlap. In
      vertebrates, ND4 and ND4L are transcribed as one bicistronic mRNA, and are
      therefore localized together. The same organization is also found in crustaceans,
      with the exceptions of T. japonicus, Neocalanus cristatus and L. salmonis that
      deviate from this pattern. Another exception of the L. salmonis mtDNA is that A6
      and A8 do not overlap, but are separated by several genes. The protein-coding
      genes have a bias towards AT-rich codons. The mitochondrial gene order in L.
      salmonis differs significantly from the copepods T. japonicus, Eucalanus bungii,
      N. cristatus and the other 13 crustaceans previously characterized. Furthermore,
      the mitochondrial rRNA genes are encoded on opposite strands in L. salmonis. This
      has not been found in any other arthropods, but has been reported in two starfish
      species. In a phylogenetic analysis, using an alignment of mitochondrial protein
      sequences, L. salmonis groups together with T. japonicus, being distant relatives
      to the other crustaceans.

PMID- 15987669
TI  - Performance of diadochokinetic movements in schizophrenic patients.
AB  - Motor deficits are common and disabling symptoms in schizophrenic patients, which
      have enormous impact on the long-term outcome of the disease by affecting work
      performance and daily functioning. They are attributed to the disorder itself, as
      well as to treatment with dopamine-blocking antipsychotics. This study assessed
      the kinematic parameters of motor performance of a diadochokinetic hand movement
      in 20 drug-naive, 20 conventionally treated (haloperidol or fluphenazine), and 20
      atypically treated (olanzapine) patients, as well as in 20 healthy controls using
      a three-dimensional ultrasonic movement analysis system. It also tested
      differences in motor enhancement as induced by an attentional strategy and in
      dexterity advantages of motor performance for the dominant hand between the four
      study groups. Amplitude and peak velocity of diadochokinetic hand movements were
      significantly reduced in all patient groups compared to the controls, while
      frequency of the repetitive movement remained unaffected. The reduction was most
      pronounced in the conventionally treated patients. In addition, movement
      automation was impaired, primarily under conventional antipsychotic treatment.
      The study also revealed weaker effects of an attentional enhancing strategy on
      the movement amplitude in atypically and conventionally treated patients compared
      to both controls and drug-naive patients. Alterations of dexterity could not be
      detected either in the drug-naive or in the treated patients. The results
      indicate that patients with schizophrenia suffer from a specific primary motor
      deficit in diadochokinesia with reduction of amplitude and peak velocity. This
      deficit is significantly worsened by conventional antipsychotic treatment.
      Antipsychotic treatment additionally reduces the enhancing effect of an
      attentional strategy on motor performance.

PMID- 15987670
TI  - The neural correlates of understanding the other's distress: a positron emission
      tomography investigation of accurate empathy.
AB  - The purpose of the present study was to assess the relationship between brain
      metabolism and empathic response. Six right-handed healthy volunteers were
      scanned with PET and fluorodeoxyglucose twice: during an interview about neutral
      story themes and during an empathic response eliciting interview about a story of
      a character in distress. Metabolic values in the medial and superior frontal
      gyrus, occipitotemporal cortices, thalamus and the cerebellum were higher during
      empathic response than during the neutral theme interview. Furthermore, the
      subjects' empathy scores were positively correlated with metabolism in the medial
      aspects of the superior frontal gyrus. Our results suggest that empathy consists
      of both affective and cognitive components and hence may involve cortices that
      mediate simulation of emotional processing and mental state attribution.

PMID- 15987671
TI  - Anxiety sensitivity as a predictor of labor pain.
AB  - Psychosocial factors have been implicated in the pain experience during
      childbirth, which can have both short- and long-term consequences on the mother's
      health and her relationship with her infant. The present study evaluated
      important demographic, social, and psychological factors as predictors of
      multiple dimensions of labor pain among 35 mothers during childbirth. The results
      indicated that anxiety sensitivity (AS), as measured by the Anxiety Sensitivity
      Index, shared a significant relation with maximum pain during labor as well as
      sensory and affective components of pain as measured by the McGill Pain
      Questionnaire. AS predicted both maximum pain during labor and sensory aspects of
      pain above and beyond demographic and social factors as well as other
      theoretically important psychological factors (e.g., depression and state
      anxiety). These data replicate previous research that has demonstrated the
      significant impact of AS on pain responding in other areas (e.g., chronic pain)
      and extend knowledge in this literature to demonstrate the important role that AS
      serves among women and their experience of labor pain. Clinical implications are
      highlighted and discussed.

PMID- 15987672
TI  - Enhanced efficacy of cholesterol-minus sonic hedgehog in postnatal skin.
AB  - The role of Sonic hedgehog (Shh) as a morphogen in diverse developmental settings
      depends on covalent addition of cholesterol. In this study, expression of Shh
      lacking cholesterol stimulated hair growth with greater efficacy than native Shh,
      suggesting that Shh acts as a chemokine rather than a morphogen in this postnatal
      role. Thus, a structural modification that renders a morphogen ineffective in
      developmental models may have distinct advantages for postnatal applications.

PMID- 15987673
TI  - Establishment of cementoblast cell lines from rat cementum lining cells by
      transfection with temperature-sensitive simian virus-40 T-antigen gene.
AB  - Defining the regulatory mechanisms promoting differentiation and proliferation of
      cementoblasts has not been well understood, because of the lack of cell models in
      vitro. To establish an in vitro cell model for the cementoblasts, extracted rat
      molars obtained from 8-week-old rats were used. Cells lining the root surface
      (cemetoblasts) were obtained by an enzymatic digestion method, and immediately
      immortalized by transfection of thermolabile SV40 T-antigen gene. The transfected
      cementum lining cell clones, RCM-C3 and -C4, were maintained for more than 200
      population doublings (PD), while the original cells stopped their growth at 60
      PD. Thus, immortalized cell lines decreased expression of SV40 T-antigen and
      subsequently cell proliferation at non-permissive temperature (39 degrees C).
      Reverse-transcribed-polymerase chain reaction indicated expression of gene for
      type I collagen, alkaline phosphatase (ALP), osteopontin, and osteocalcin mRNA at
      both permissive (33 degrees C) and non-permissive (39 degrees C) temperatures.
      RCM-C4 expressed higher bone siaploprotein (BSP) mRNA than RCM-C3, and further
      RCM-C4 showed higher BSP mRNA at 39 degrees C than 33 degrees C. High ALP
      activity and mineralized nodule formation were observed at 39 degrees C in both
      cell lines. These findings suggested that the cell lines, RCM-C3 and -C4, are
      useful model for studying the regulatory mechanisms of differentiation and
      proliferation of cementoblasts.

PMID- 15987674
TI  - Identification of novel resident pulmonary stem cells: form and function of the
      lung side population.
AB  - Resident lung stem cells function to replace all lineages of pulmonary tissue,
      including mesenchyme, epithelium, and vasculature. The phenotype of the lung side
      population (SP) cells is currently under investigation; their function is
      currently unknown. Recent data suggest lung SP cells are an enriched tissue
      specific source of organ-specific pulmonary precursors and, therefore, a source
      of adult stem cells. The adult lung SP cell population has been isolated and
      characterized for expression of markers indicative of stem cell, epithelial, and
      mesenchymal lineages. These studies determined that the adult mouse lung SP has
      epithelial and mesenchymal potential that resides within a CD45- mesenchymal
      subpopulation, as well as limited hematopoietic ability, which resides in the
      bone marrow-derived CD45+ subpopulation. The ability to identify these adult lung
      precursor cells allows us to further study the potential of these cells and their
      role in the regulation of tissue homeostasis and response to injury. The
      identification of this target population will potentially allow earlier treatment
      and, long term, a functional restoration of injured pulmonary tissue and lung
      health.

PMID- 15987675
TI  - How family 26 glycoside hydrolases orchestrate catalysis on different
      polysaccharides: structure and activity of a Clostridium thermocellum lichenase,
      CtLic26A.
AB  - One of the most intriguing features of the 90 glycoside hydrolase families (GHs)
      is the range of specificities displayed by different members of the same family,
      whereas the catalytic apparatus and mechanism are often invariant. Family GH26
      predominantly comprises beta-1,4 mannanases; however, a bifunctional Clostridium
      thermocellum GH26 member (hereafter CtLic26A) displays a markedly different
      specificity. We show that CtLic26A is a lichenase, specific for mixed
      (Glcbeta1,4Glcbeta1,4Glcbeta1,3)n oligo- and polysaccharides, and displays no
      activity on manno-configured substrates or beta-1,4-linked homopolymers of
      glucose or xylose. The three-dimensional structure of the native form of CtLic26A
      has been solved at 1.50-A resolution, revealing a characteristic (beta/alpha)8
      barrel with Glu-109 and Glu-222 acting as the catalytic acid/base and nucleophile
      in a double-displacement mechanism. The complex with the competitive inhibitor,
      Glc-beta-1,3-isofagomine (Ki 1 microm), at 1.60 A sheds light on substrate
      recognition in the -2 and -1 subsites and illuminates why the enzyme is specific
      for lichenan-based substrates. Hydrolysis of beta-mannosides by GH26 members is
      thought to proceed through transition states in the B2,5 (boat) conformation in
      which structural distinction of glucosides versus mannosides reflects not the
      configuration at C2 but the recognition of the pseudoaxial O3 of the B2,5
      conformation. We suggest a different conformational itinerary for the GH26
      enzymes active on gluco-configured substrates.

PMID- 15987676
TI  - Specificity of protein interactions mediated by BRCT domains of the XRCC1 DNA
      repair protein.
AB  - Protein interactions critical to DNA repair and cell cycle control systems are
      often coordinated by modules that belong to a superfamily of structurally
      conserved BRCT domains. Because the mechanisms of BRCT interactions and their
      significance are not well understood, we sought to define the affinity and
      specificity of those BRCT modules that orchestrate base excision repair and
      single-strand break repair. Common to these pathways is the essential XRCC1 DNA
      repair protein, which interacts with at least nine other proteins and DNA. Here,
      we characterized the interactions of four purified BRCT domains, two from XRCC1
      and their two partners from DNA ligase IIIalpha and poly(ADP-ribosyl) polymerase
      1. A monoclonal antibody was selected that recognizes the ligase IIIalpha BRCT
      domain, but not the other BRCT domains, and was used to capture the relevant
      ligase IIIalpha BRCT complex. To examine the assembly states of isolated BRCT
      domains and pairwise domain complexes, we used size-exclusion chromatography
      coupled with on-line light scattering. This analysis indicated that isolated BRCT
      domains form homo-oligomers and that the BRCT complex between the C-terminal
      XRCC1 domain and the ligase IIIalpha domain is a heterotetramer with 2:2
      stoichiometry. Using affinity capture and surface plasmon resonance methods, we
      determined that specific heteromeric interactions with high nanomolar
      dissociation constants occur between pairs of cognate BRCT domains. A structural
      model for a XRCC1 x DNA ligase IIIalpha heterotetramer is proposed as a core base
      excision repair complex, which constitutes a scaffold for higher order complexes
      to which other repair proteins and DNA are brought into proximity.

PMID- 15987677
TI  - p300/CBP-associated factor drives DEK into interchromatin granule clusters.
AB  - DEK is a mammalian protein that has been implicated in the pathogenesis of
      autoimmune diseases and cancer, including acute myeloid leukemia, melanoma,
      glioblastoma, hepatocellular carcinoma, and bladder cancer. In addition, DEK
      appears to participate in multiple cellular processes, including transcriptional
      repression, mRNA processing, and chromatin remodeling. Sub-nuclear distribution
      of this protein, with the attendant functional ramifications, has remained a
      controversial topic. Here we report that DEK undergoes acetylation in vivo at
      lysine residues within the first 70 N-terminal amino acids. Acetylation of DEK
      decreases its affinity for DNA elements within the promoter, which is consistent
      with the involvement of DEK in transcriptional repression. Furthermore,
      deacetylase inhibition results in accumulation of DEK within interchromatin
      granule clusters (IGCs), sub-nuclear structures that contain RNA processing
      factors. Overexpression of P/CAF acetylase drives DEK into IGCs, and addition of
      a newly developed, synthetic, cell-permeable P/CAF inhibitor blocks this
      movement. To our knowledge, this is the first reported example of acetylation
      playing a direct role in relocation of a protein to IGCs, and this may explain
      how DEK can function in multiple pathways that take place in distinct sub-nuclear
      compartments. These findings also suggest that DEK-associated malignancies and
      autoimmune diseases might be amenable to treatment with agents that alter
      acetylation.

PMID- 15987678
TI  - Multiple GTF2I-like repeats of general transcription factor 3 exhibit DNA binding
      properties. Evidence for a common origin as a sequence-specific DNA interaction
      module.
AB  - A hallmark of general transcription factor 3 (GTF3) is the presence of multiple
      GTF2I-like repeats that were suggested to mediate protein-protein interactions.
      However, we have recently demonstrated that repeat 4 is necessary and sufficient
      for binding of GTF3 to the bicoid-like motif of the Troponin I slow enhancer.
      Given the sequence similarity between different GTF2I-like repeats we
      hypothesized that DNA binding might be a common property of this domain type. We
      subjected five repeats of GTF3 to random oligonucleotide selection (SELEX) to
      assess their DNA binding potentials. We delineated the consensus sequence
      G(TC)G(A)GATTA(G)BG(A) for repeat 4 and showed that binding sites for GTF3 in
      enhancers for Troponin I and homeobox c8 (HOXc8) are in very good agreement with
      this motif. SELEX selections for repeats 5 and 2 enriched for oligonucleotides
      that were also bound by R4, suggesting that they share common sequence
      preferences, whereas repeat 3 exhibited relaxed sequence requirements for DNA
      binding. No binding was observed for repeat 1. We also show that GTF2I-like
      repeats 4 and 6 of transcription factor II-I (TFII-I) exhibit modest DNA binding
      properties. Lastly, we identified several amino acids of GTF3 repeat 4 required
      for high affinity protein-DNA interaction. Based on the ability of many repeats
      to bind DNA in vitro, we suggest that GTF2I-like domains evolved by duplication
      and diversification of a prototypic DNA-binding ancestor.

PMID- 15987679
TI  - The MUC1 SEA module is a self-cleaving domain.
AB  - MUC1, a glycoprotein overexpressed by a variety of human adenocarcinomas, is a
      type I transmembrane protein (MUC1/TM) that soon after its synthesis undergoes
      proteolytic cleavage in its extracellular domain. This cleavage generates two
      subunits, alpha and beta, that specifically recognize each other and bind
      together in a strong noncovalent interaction. Proteolysis occurs within the SEA
      module, a 120-amino acid domain that is highly conserved in a number of heavily
      glycosylated mucin-like proteins. Post-translational cleavage of the SEA module
      occurs at a site similar to that in MUC1 in the glycoproteins IgHepta and MUC3.
      However, as in the case of other proteins containing the cleaved SEA module, the
      mechanism of MUC1 proteolysis has not been elucidated. Alternative splicing
      generates two transmembrane MUC1 isoforms, designated MUC1/Y and MUC1/X. We
      demonstrated here that MUC1/X, whose extracellular domain is comprised solely of
      the SEA module in addition to 30 MUC1 N-terminal amino acids, undergoes
      proteolytic cleavage at the same site as the MUC1/TM protein. In contrast, the
      MUC1/Y isoform, composed of an N-terminally truncated SEA module, is not cleaved.
      Cysteine or threonine mutations of the MUC1/X serine residue (Ser-63) immediately
      C-terminal to the cleavage site generated cleaved proteins, whereas mutation of
      the Ser-63 residue of MUC1/X to any other of 17 amino acids did not result in
      cleavage. In vitro incubation of highly purified precursor MUC1/X protein
      resulted in self-cleavage. Furthermore, addition of hydroxylamine, a strong
      nucleophile, markedly enhanced cleavage. Both these features are signature
      characteristics of self-cleaving proteins, and we concluded that MUC1 undergoes
      autoproteolysis mediated by an N --> O-acyl rearrangement at the cleavage site
      followed by hydrolytic resolution of the unstable ester and concomitant cleavage.
      It is likely that all cleaved SEA module-containing proteins follow a similar
      route.

PMID- 15987681
TI  - JLP associates with kinesin light chain 1 through a novel leucine zipper-like
      domain.
AB  - Scaffolding proteins exist in eukaryotes to properly assemble signaling proteins
      into specific multimeric functional complexes. JLP is a novel leucine zipper
      protein belonging to a family of scaffolding proteins that assemble JNK signaling
      modules. JLP is a proline-rich protein that contains two leucine zipper domains
      and a highly conserved C-terminal domain. We have identified kinesin light chain
      1 (KLC1) as a binding partner for the second leucine zipper domain of JLP using
      yeast two-hybrid screening. The interaction domain of KLC1 was mapped to its
      tetratripeptide repeat, which contains a novel leucine zipper-like domain that is
      crucial for the interaction with JLP. Mutations of Leu-280, Leu-287, Val-294, and
      Leu-301 within this domain of KLC1 disrupted its ability to associate with JLP.
      Immunofluorescence studies showed that JLP and KLC1 co-localized in the cytoplasm
      and that the localization of JLP was dependent on its second leucine zipper.
      Ectopic expression of a dominant negative form of KLC1 resulted in the
      mislocalization of endogenous JLP. Moreover, the association between JLP and KLC1
      occurred in vivo and was important in the formation of ternary complex with JNK1.
      These results identify a novel protein-protein interaction between KLC1 and JLP
      that involves leucine zipper-like domains and support the role of motor proteins
      in the spatial regulation of signaling modules.

PMID- 15987680
TI  - Interplay of Ca2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell
      line.
AB  - Ca2+ and cAMP are important second messengers that regulate multiple cellular
      processes. Although previous studies have suggested direct interactions between
      Ca2+ and cAMP signaling pathways, the underlying mechanisms remain unresolved. In
      particular, direct evidence for Ca2+-regulated cAMP production in living cells is
      incomplete. Genetically encoded fluorescence resonance energy transfer-based
      biosensors have made possible real-time imaging of spatial and temporal gradients
      of intracellular cAMP concentration in single living cells. Here, we used
      confocal microscopy, fluorescence resonance energy transfer, and insulin
      secreting MIN6 cells expressing Epac1-camps, a biosynthetic unimolecular cAMP
      indicator, to better understand the role of intracellular Ca2+ in cAMP
      production. We report that depolarization with high external K+, tolbutamide, or
      glucose caused a rapid increase in cAMP that was dependent on extracellular Ca2+
      and inhibited by nitrendipine, a Ca2+ channel blocker, or 2',5'-dideoxyadenosine,
      a P-site antagonist of transmembrane adenylate cyclases. Stimulation of MIN6
      cells with glucose in the presence of tetraethylammonium chloride generated
      concomitant Ca2+ and cAMP oscillations that were abolished in the absence of
      extracellular Ca2+ and blocked by 2',5'-dideoxyadenosine or 3-isobutyl-1
      methylxanthine, an inhibitor of phosphodiesterase. Simultaneous measurements of
      Ca2+ and cAMP concentrations with Fura-2 and Epac1-camps, respectively, revealed
      a close temporal and causal interrelationship between the increases in
      cytoplasmic Ca2+ and cAMP levels following membrane depolarization. These
      findings indicate highly coordinated interplay between Ca2+ and cAMP signaling in
      electrically excitable endocrine cells and suggest that Ca2+-dependent cAMP
      oscillations are derived from an increase in adenylate cyclase activity and
      periodic activation and inactivation of cAMP-hydrolyzing phosphodiesterase.

PMID- 15987682
TI  - Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type
      mitochondrial aspartate-glutamate carrier.
AB  - Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly
      distributed in brain and skeletal muscle, involved in the transport of aspartate
      from mitochondria to cytosol, and in the transfer of cytosolic reducing
      equivalents into mitochondria as a member of the malate-aspartate NADH shuttle.
      In the present study, we describe the characteristics of aralar-deficient (Aralar
      /-) mice, generated by a gene-trap method, showing no aralar mRNA and protein,
      and no detectable malate-aspartate shuttle activity in skeletal muscle and brain
      mitochondria. Aralar-/- mice were growth-retarded, exhibited generalized
      tremoring, and had pronounced motor coordination defects along with an impaired
      myelination in the central nervous system. Analysis of lipid components showed a
      marked decrease in the myelin lipid galactosyl cerebroside. The content of the
      myelin lipid precursor, N-acetylaspartate, and that of aspartate are drastically
      decreased in the brain of Aralar-/- mice. The defect in N-acetylaspartate
      production was also observed in cell extracts from primary neuronal cultures
      derived from Aralar-/- mouse embryos. These results show that aralar plays an
      important role in myelin formation by providing aspartate for the synthesis of N
      acetylaspartate in neuronal cells.

PMID- 15987683
TI  - Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice.
AB  - Beta-secretase (BACE1) is the rate-limiting protease for the generation of the
      amyloid beta-peptide (Abeta) in Alzheimer disease. Mice in which the bace1 gene
      is inactivated are reported to be healthy. However, the presence of a homologous
      gene encoding BACE2 raises the possibility of compensatory mechanisms. Therefore,
      we have generated bace1, bace2, and double knockout mice. We report here that
      BACE1 mice display a complex phenotype. A variable but significant number of
      BACE1 offspring died in the first weeks after birth. The surviving mice remained
      smaller than their littermate controls and presented a hyperactive behavior.
      Electrophysiologically, subtle alterations in the steady-state inactivation of
      voltage-gated sodium channels in BACE1-deficient neurons were observed. In
      contrast, bace2 knockout mice displayed an overall healthy phenotype. However, a
      combined deficiency of BACE2 and BACE1 enhanced the bace1-/- lethality phenotype.
      At the biochemical level, we have confirmed that BACE1 deficiency results in an
      almost complete block of Abeta generation in neurons, but not in glia. As glia
      are 10 times more abundant in brain compared with neurons, our data indicate that
      BACE2 could indeed contribute to Abeta generation in the brains of Alzheimer
      disease and, in particular, Down syndrome patients. In conclusion, our data
      challenge the general idea of BACE1 as a safe drug target and call for some
      caution when claiming that no major side effects should be expected from blocking
      BACE1 activity.

PMID- 15987684
TI  - Calmodulin and calcium interplay in the modulation of TRPC5 channel activity.
      Identification of a novel C-terminal domain for calcium/calmodulin-mediated
      facilitation.
AB  - TRPC5 forms Ca2+-permeable nonselective cation channels important for neurite
      outgrowth and growth cone morphology of hippocampal neurons. Here we studied the
      activation of mouse TRPC5 expressed in Chinese hamster ovary and human embryonic
      kidney 293 cells by agonist stimulation of several receptors that couple to the
      phosphoinositide signaling cascade and the role of calmodulin (CaM) on the
      activation. We showed that exogenous application of 10 microM CaM through patch
      pipette accelerated the agonist-induced channel activation by 2.8-fold, with the
      time constant for half-activation reduced from 4.25 +/- 0.4 to 1.56 +/- 0.85 min.
      We identified a novel CaM-binding site located at the C terminus of TRPC5, 95
      amino acids downstream from the previously determined common CaM/IP3R-binding
      (CIRB) domain for all TRPC proteins. Deletion of the novel CaM-binding site
      attenuated the acceleration in channel activation induced by CaM. However,
      disruption of the CIRB domain from TRPC5 rendered the channel irresponsive to
      agonist stimulation without affecting the cell surface expression of the channel
      protein. Furthermore, we showed that high (>5 microM) intracellular free Ca2+
      inhibited the current density without affecting the time course of TRPC5
      activation by receptor agonists. These results demonstrated that intracellular
      Ca2+ has dual and opposite effects on the activation of TRPC5. The novel CaM
      binding site is important for the Ca2+/CaM-mediated facilitation, whereas the
      CIRB domain is critical for the overall response of receptor-induced TRPC5
      channel activation.

PMID- 15987685
TI  - Diverse biochemical properties of Shp2 mutants. Implications for disease
      phenotypes.
AB  - Mutations in the Src homology 2 (SH2)-containing protein-tyrosine phosphatase
      Shp2 (PTPN11) underlie half of the cases of the autosomal dominant genetic
      disorder Noonan syndrome, and somatic Shp2 mutations are found in several
      hematologic and solid malignancies. Earlier studies of small numbers of mutants
      suggested that disease-associated mutations cause constitutive (SH2 binding
      independent) activation and that cancer-associated mutants are more active than
      those associated with Noonan syndrome. We have characterized a larger panel of
      Shp2 mutants and find that this "activity-centric" model cannot explain the
      behaviors of all pathogenic Shp2 mutations. Instead, enzymatic, structural, and
      mathematical modeling analyses show that these mutants can affect basal
      activation, SH2 domain-phosphopeptide affinity, and/or substrate specificity to
      varying degrees. Furthermore, there is no absolute correlation between the
      mutants' extents of basal activation and the diseases they induce. We propose
      that activated mutants of Shp2 modulate signaling from specific stimuli to a
      subset of effectors and provide a theoretical framework for understanding the
      complex relationship between Shp2 activation, intracellular signaling, and
      pathology.

PMID- 15987686
TI  - The rise and fall of the chemoattractant receptor GPR33.
AB  - Chemokine and chemoattractant receptors are members of the large superfamily of G
      protein-coupled receptors (GPCR), which control leukocyte chemotaxis. In addition
      to their physiological role, several chemokine and chemoattractant receptors,
      such as CCR5 and Duffy, have been directly associated with pathogen entry. GPR33
      is an orphan chemoattractant GPCR that was previously identified as a pseudogene
      in humans. GPR33 evolved in mammals about 125-190 million years ago. The cloning
      and analysis of more than 120 mammalian GPR33 orthologs from 16 of 18 eutherian
      orders revealed an inactivation of this chemoattractant GPCR not only in humans,
      but also in several great ape and rodent species. Intriguingly, in all ape and
      some rodent species where the inactivation occurred, samples harbored both
      pseudogene and intact gene variants. The analysis of over 1200 human individuals
      representing all major linguistic groups revealed that the intact allele of GPR33
      is still present in the human population. Estimates of the age of the human
      alleles suggest inactivation in the past 1 million years. Similarly, analysis of
      more than 120 wild-caught gray rats (Rattus norvegicus), revealed that
      inactivation of gpr33 is worldwide fixed and occurred in less than 0.7 million
      years ago. The coincidental inactivation and its fixation in several species of
      distantly related mammalian orders suggest a selective pressure on this
      chemoattractant receptor gene.

PMID- 15987687
TI  - Crystal structure of the Actinomadura R39 DD-peptidase reveals new domains in
      penicillin-binding proteins.
AB  - Actinomadura sp. R39 produces an exocellular DD-peptidase/penicillin-binding
      protein (PBP) whose primary structure is similar to that of Escherichia coli
      PBP4. It is characterized by a high beta-lactam-binding activity (second order
      rate constant for the acylation of the active site serine by benzylpenicillin:
      k2/K = 300 mm(-1) s(-1)). The crystal structure of the DD-peptidase from
      Actinomadura R39 was solved at a resolution of 1.8 angstroms by single anomalous
      dispersion at the cobalt resonance wavelength. The structure is composed of three
      domains: a penicillin-binding domain similar to the penicillin-binding domain of
      E. coli PBP5 and two domains of unknown function. In most multimodular PBPs,
      additional domains are generally located at the C or N termini of the penicillin
      binding domain. In R39, the other two domains are inserted in the penicillin
      binding domain, between the SXXK and SXN motifs, in a manner similar to
      "Matryoshka dolls." One of these domains is composed of a five-stranded beta
      sheet with two helices on one side, and the other domain is a double three
      stranded beta-sheet inserted in the previous domain. Additionally, the 2.4
      angstroms structure of the acyl-enzyme complex of R39 with nitrocefin reveals the
      absence of active site conformational change upon binding the beta-lactams.

PMID- 15987688
TI  - Peptide blockers of the inhibition of neuronal nicotinic acetylcholine receptors
      by amyloid beta.
AB  - Alzheimer disease (AD) is characterized by accumulation of the neurotoxic amyloid
      beta peptide (Abeta) and by the loss of cholinergic neurons and nicotinic
      acetylcholine receptors (nAChRs) throughout the brain. Direct inhibition of
      nAChRs by Abeta has also been suggested to contribute to cholinergic dysfunction
      in AD. In an effort to find ligands capable of blocking Abeta-induced inhibition
      of nAChRs, we have screened a phage display library to identify peptides that
      bind to Abeta. Using this approach, we identified a heptapeptide denoted IQ,
      which binds with nanomolar affinity to Abeta and is homologous to the
      acetylcholine-binding protein and to most subtypes of nAChRs. Rapid kinetic whole
      cell current-recording measurements showed that Abeta inhibits nAChR function in
      a dose-dependent manner in neuronal differentiated PC12 cells and that nanomolar
      concentrations of IQ completely block the inhibition by Abeta. These results
      indicate that the Abeta binding site in nAChRs is homologous to the IQ peptide
      and that this is a relevant target for Abeta neurotoxicity in AD and, more
      generally, for the regulation of nAChR function by soluble Abeta in a
      physiological context. Furthermore, the results suggest that the IQ peptide may
      be a lead for the development of novel drugs to block the inhibition of nAChRs in
      AD.

PMID- 15987689
TI  - Ca2+/calmodulin-dependent protein kinase II is an essential mediator in the
      coordinated regulation of electrocyte Ca2+-ATPase by calmodulin and protein
      kinase A.
AB  - The aim of this study was to investigate (a) whether Ca2+/calmodulin-dependent
      protein kinase II (CaM kinase II) participates in the regulation of plasma
      membrane Ca2+-ATPase and (b) its possible cross-talk with other kinase-mediated
      modulatory pathways of the pump. Using isolated innervated membranes of the
      electrocytes from Electrophorus electricus L., we found that stimulation of
      endogenous protein kinase A (PKA) strongly phosphorylated membrane-bound CaM
      kinase II with simultaneous substantial activation of the Ca2+ pump
      (approximately 2-fold). The addition of cAMP (5-50 pM), forskolin (10 nM), or
      cholera toxin (10 or 100 nM) stimulated both CaM kinase II phosphorylation and
      Ca2+-ATPase activity, whereas these activation processes were cancelled by an
      inhibitor of the PKA alpha-catalytic subunit. When CaM kinase II was blocked by
      its specific inhibitor KN-93, the Ca2+-ATPase activity decreased to the levels
      measured in the absence of calmodulin; the unusually high Ca2+ affinity dropped 2
      fold; and the PKA-mediated stimulation of Ca2+-ATPase was no longer seen.
      Hydroxylamine-resistant phosphorylation of the Ca2+-ATPase strongly increased
      when the PKA pathway was activated, and this phosphorylation was suppressed by
      inhibition of CaM kinase II. We conclude that CaM kinase II is an intermediate in
      a complex regulatory network of the electrocyte Ca2+ pump, which also involves
      calmodulin and PKA.

PMID- 15987690
TI  - Clavulanic acid inactivation of SHV-1 and the inhibitor-resistant S130G SHV-1
      beta-lactamase. Insights into the mechanism of inhibition.
AB  - Clavulanic acid is a potent mechanism-based inhibitor of TEM-1 and SHV-1beta
      lactamases, enzymes that confer resistance to beta-lactams in many gram-negative
      pathogens. This compound has enjoyed widespread clinical use as part of beta
      lactam beta-lactamase inhibitor therapy directed against penicillin-resistant
      pathogens. Unfortunately, the emergence of clavulanic acid-resistant variants of
      TEM-1 and SHV-1 beta-lactamase significantly compromise the efficacy of this
      combination. A single amino acid change at Ambler position Ser130 (Ser --> Gly)
      results in resistance to inactivation by clavulanate in the SHV-1 and TEM-1beta
      lactamases. Herein, we investigated the inactivation of SHV-1 and the inhibitor
      resistant S130G variant beta-lactamases by clavulanate. Using liquid
      chromatography electrospray ionization mass spectrometry, we detected multiple
      modified proteins when SHV-1 beta-lactamase is inactivated by clavulanate. Matrix
      assisted laser desorption ionization-time of flight mass spectrometry was used to
      study tryptic digests of SHV-1 and S130Gbeta-lactamases (+/- inactivation with
      clavulanate) and identified peptides modified at the active site Ser70.
      Ultraviolet (UV) difference spectral studies comparing SHV-1 and S130Gbeta
      lactamases inactivated by clavulanate showed that the formation of reaction
      intermediates with absorption maxima at 227 and 280 nm are diminished and delayed
      when S130Gbeta-lactamase is inactivated. We conclude that the clavulanic acid
      inhibition of the S130G beta-lactamase must follow a branch of the normal
      inactivation pathway. These findings highlight the importance of understanding
      the intermediates formed in the inactivation process of inhibitor-resistant beta
      lactamases and suggest how strategic chemical design can lead to novel ways to
      inhibit beta-lactamases.

PMID- 15987692
TI  - Structural characterization of calcineurin B homologous protein 1.
AB  - Calcineurin B homologous protein 1 (CHP1), also known as p22, is a calcium
      binding EF-hand protein that plays a role in membrane trafficking. It binds to
      multiple effector proteins, including Na(+)/H(+) exchangers, a serine/threonine
      kinase, and calcineurin, potentially modulating their function. The crystal
      structure of calcium-bound CHP1 from rat has been determined at 2.2 Angstroms of
      resolution. The molecule has a compact alpha-helical structure containing four EF
      hands. The overall folding topology of the protein is similar to that of the
      regulatory B subunit of calcineurin and to that of calcium- and integrin-binding
      protein. The calcium ion is coordinated in typical fashion in the third and
      fourth EF-hands, but the first and second EF-hands contain no calcium ion. The
      first EF-hand is maintained by internal interactions, and the second EF-hand is
      stabilized by hydrophobic interactions. CHP1 contains a hydrophobic pocket on the
      opposite side of the protein to the EF-hands that has been implicated in ligand
      binding.

PMID- 15987691
TI  - Expression of scavenger receptors in glial cells. Comparing the adhesion of
      astrocytes and microglia from neonatal rats to surface-bound beta-amyloid.
AB  - Astrocytes and microglia associate to amyloid plaques, a pathological hallmark of
      Alzheimer disease. Microglia are activated by and can phagocytose beta-amyloid
      (Abeta). Scavenger receptors (SRs) are among the receptors mediating the uptake
      of fibrillar Abeta in vitro. However, little is known about the function of the
      astrocytes surrounding the plaques or the nature of their interaction with Abeta.
      It is unknown whether glial cells bind to nonfibrillar Abeta and if binding of
      astrocytes to Abeta depends on the same Scavenger receptors described for
      microglia. We determined the binding of glia to Abeta by an adhesion assay and
      evaluated the presence of scavenger receptors in glial cells by
      immunocytochemistry, immunohistochemistry of brain sections, and immunoblot. We
      found that astrocytes and microglia from neonatal rats adhered in a concentration
      dependent manner to surfaces coated with fibrillar Abeta or nonfibrillar Abeta.
      Fucoidan and poly(I), known ligands for SR-type A, inhibited adhesion of
      microglia and astrocytes to Abeta and also inhibited Abeta phagocytosis. In
      contrast, a ligand for SR-type B like low density lipoprotein, did not compete
      glial adhesion to Abeta. Microglia presented immunodetectable SR-BI, SR-AI/AII,
      RAGE, and SR-MARCO (macrophage receptor with collagenous structure, a member of
      the SR-A family). Astrocytes presented SR-BI and SR-MARCO. To our knowledge, this
      is the first description of the presence of SR-MARCO in astrocytes. Our results
      indicate that both microglia and astrocytes adhere to fibrillar and nonfibrillar
      Abeta. Adhesion was mediated by a fucoidan-sensitive receptor. We propose that SR
      MARCO could be the Scavenger receptor responsible for the adhesion of astrocytes
      and microglia to Abeta.

PMID- 15987693
TI  - Involvement of intracellular Ca2+ levels in nonsteroidal anti-inflammatory drug
      induced apoptosis.
AB  - We recently reported that nonsteroidal anti-inflammatory drug (NSAID)-induced
      gastric lesions involve NSAID-induced apoptosis of gastric mucosal cells, which
      in turn involves the endoplasmic reticulum stress response, in particular the up
      regulation of CCAAT/enhancer-binding protein homologous transcription factor
      (CHOP). In this study, we have examined the molecular mechanism governing this
      NSAID-induced apoptosis in primary cultures of gastric mucosal cells. Various
      NSAIDs showed membrane permeabilization activity that correlated with their
      apoptosis-inducing activity. Various NSAIDs, particularly celecoxib, also
      increased intracellular Ca2+ levels. This increase was accompanied by K+ efflux
      from cells and was virtually absent when extracellular Ca2+ had been depleted.
      These data indicate that the increase in intracellular Ca2+ levels that is
      observed in the presence of NSAIDs is due to the stimulation of Ca2+ influx
      across the cytoplasmic membrane, which results from their membrane
      permeabilization activity. An intracellular Ca2+ chelator partially inhibited
      celecoxib-induced release of cytochrome c from mitochondria, reduced the
      magnitude of the celecoxib-induced decrease in mitochondrial membrane potential
      and inhibited celecoxib-induced apoptotic cell death. It is therefore likely that
      an increase in intracellular Ca2+ levels is involved in celecoxib-induced
      mitochondrial dysfunction and the resulting apoptosis. An inhibitor of calpain, a
      Ca2+-dependent cysteine protease, partially suppressed mitochondrial dysfunction
      and apoptosis in the presence of celecoxib. Celecoxib-dependent CHOP-induction
      was partially inhibited by the intracellular Ca2+ chelator but not by the calpain
      inhibitor. These results suggest that Ca2+-stimulated calpain activity and CHOP
      expression play important roles in celecoxib-induced apoptosis in gastric mucosal
      cells.

PMID- 15987695
TI  - Unusual metaxylem tracheids in petioles of Amorphophallus (Araceae) giant leaves.
AB  - BACKGROUND AND AIMS: Petioles of huge solitary leaves of mature plants of
      Amorphophallus resemble tree trunks supporting an umbrella-like crown. Since they
      may be 4 m tall, adaptations to water transport in the petioles are as important
      as adaptations to mechanical support of lamina. The petiole is a cylindrical
      shell composed of compact unlignified tissue with a honeycomb aerenchymatous
      core. In both parts numerous vascular bundles occur, which are unique because of
      the scarcity of lignified elements. In the xylemic part of each bundle there is a
      characteristic canal with unlignified walls. The xylem pecularities are described
      and interpreted. MATERIAL: Vascular bundles in mature petioles of Amorphophallus
      titanum and A. gigas plants were studied using light and scanning electron
      microscopy. KEY RESULTS: The xylemic canal represents a file of huge metaxylem
      tracheids (diameter 55-200 microm, length >30 mm) with unlignified lateral walls
      surrounded by turgid parenchyma cells. Only their end walls, orientated steeply,
      have lignified secondary thickenings. The file is accompanied by a strand of
      narrow tracheids with lignified bar-type secondary walls, which come into direct
      contact with the wide tracheid in many places along its length. CONCLUSIONS: The
      metaxylem tracheids in A. petioles are probably the longest and widest tracheids
      known. Only their end walls have lignified secondary thickenings. Tracheids are
      long due to enormous intercalary elongation and wide due to a transverse growth
      mechanism similar to that underlying formation of aerenchyma cavities. The lack
      of lignin in lateral walls shifts the function of 'pipe walls' to the turgid
      parenchyma paving the tracheid. The analogy to carinal canals of Equisetum, as
      well as other protoxylem lacunas is discussed. The stiff partitions between the
      long and wide tracheids are interpreted as structures similar to the end walls in
      vessels.

PMID- 15987694
TI  - Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty
      acid amide hydrolase-dependent arachidonic acid conjugation in the nervous
      system.
AB  - Acetaminophen (paracetamol) is a popular domestic analgesic and antipyretic agent
      with a weak anti-inflammatory action and a low incidence of adverse effects as
      compared with aspirin and other non-steroidal anti-inflammatory drugs. Here we
      show that acetaminophen, following deacetylation to its primary amine, is
      conjugated with arachidonic acid in the brain and the spinal cord to form the
      potent TRPV1 agonist N-arachidonoylphenolamine (AM404). This conjugation is
      absent in mice lacking the enzyme fatty acid amide hydrolase. AM404 also inhibits
      purified cyclooxygenase (COX)-1 and COX-2 and prostaglandin synthesis in
      lipopolysaccharide-stimulated RAW264.7 macrophages. This novel metabolite of
      acetaminophen also acts on the endogenous cannabinoid system, which, together
      with TRPV1 and COX, is present in the pain and thermoregulatory pathways. These
      findings identify fatty acid conjugation as a novel pathway for drug metabolism
      and provide a molecular mechanism for the occurrence of the analgesic N
      acylphenolamine AM404 in the nervous system following treatment with
      acetaminophen.

PMID- 15987696
TI  - Distribution of fertility-restorer genes for wild-abortive and Honglian CMS lines
      of rice in the AA genome species of genus Oryza.
AB  - BACKGROUND AND AIMS: Rice (Oryza sativa) is one of the most important cereal
      plants in the world. Wild-abortive (WA) and Honglian (HL) cytoplasmic male
      sterility (CMS) have been used extensively in the production of hybrid seeds.
      Although a variable number of fertility-restorer genes (Rf) for WA and HL-CMS
      have been identified in various cultivars, information on Rf in Oryza species
      with the AA-genome is sparse. Therefore the distribution and heredity of Rf for
      WA and HL-CMS in wild rice species of Oryza with the AA-genome were investigated.
      METHODS: Fertility-restorer genes for WA and HL-CMS in wild rice species with the
      AA-genome were investigated by following the fertility of microspores identified
      by I2-KI staining and by following the seed-setting rate of spikelets. A genetic
      model of Rf in some selected restorer accessions was analysed based on the
      fertility segregation of BC1F1 populations. KEY RESULTS: Fertility analysis
      showed that 21 out of 35 HL-type F1s, and 13 out of 31 WA-type F1s were scored as
      fertile. The frequency of Rf in wild rice was 60% for HL-CMS and 41.9% for WA
      CMS, respectively. The fertility-restorer accessions, especially those with
      complete restoring ability, aggregated mainly in two species of O. rufipogon and
      O. nivara. The wild rice accessions with Rf for HL-CMS were distributed in Asia,
      Oceania, Latin American and Africa, but were centered mainly in Asia, whilst the
      wild restorer accessions for WA-CMS were limited only to Asia and Africa. Apart
      from one restorer accession that possessed two pairs of Rf for WA-CMS, all of the
      other nine tested wild restorer accessions each contained only a single Rf for WA
      CMS or HL-CMS. Allele analysis indicated that there existed at least three Rf
      loci for the WA and HL-CMS systems. CONCLUSIONS: These data support the
      hypothesis that fertility-restorer genes exist widely in Oryza species with the
      AA-genome, and that Rf in Oryza sativa originated from the Oryza rufipogon/Oryza
      nivara complex, the ancestor of cultivated rice in Asia. The origin and evolution
      of Rf is tightly linked to that of CMS in wild rice, and fertility of a given CMS
      type is controlled by several Rf alleles in various wild restorer accessions.

PMID- 15987697
TI  - The distribution of aquaporin subtypes (PIP1, PIP2 and gamma-TIP) is tissue
      dependent in soybean (Glycine max) root nodules.
AB  - BACKGROUND AND AIMS The inner cortical cells (IC-cells) of legume root nodules
      have been previously shown to regulate the resistance to nodule O2 diffusion by a
      rapid contraction/expansion mechanism, which controls the volume of intercellular
      spaces and their occlusion by a liquid phase. The expression of aquaporins in IC
      cells was also found to be involved in this nodule O2 diffusion mechanism. The
      aim of this study was to compare the expression of plasma membrane intrinsic
      proteins (PIP) aquaporin isoforms with tonoplast intrinsic protein (gamma-TIP) in
      both IC-cells and adjacent cell types. METHODS: Using immunogold labelling in
      ultra-thin sections of Glycine max nodules, the expression of two PIP isoforms
      was observed and compared with the gamma-TIP pattern. KEY RESULTS: The plasma
      membrane aquaporins PIP1 and PIP2 were expressed more in IC-cells and endodermis
      than in pericycle and infected cells. The tonoplast aquaporin gamma-TIP has shown
      a distribution pattern similar to that of the PIPs. CONCLUSIONS: PIPs and gamma
      TIP aquaporins are highly expressed in both plasmalemma and tonoplast of nodule
      IC-cells. This distribution is consistent with the putative role of water fluxes
      associated with the regulation of nodule conductance to O2 diffusion and the
      subsequent ATP-dependent nitrogenase activity. In the endodermis, these
      aquaporins might also be involved in nutrient transport between the infected zone
      and vascular traces.

PMID- 15987698
TI  - Factors influencing recombination frequency and distribution in a human meiotic
      crossover hotspot.
AB  - Little is known about the factors that influence the frequency and distribution
      of meiotic recombination events within human crossover hotspots. We now describe
      the detailed analysis of sperm recombination in the NID1 hotspot. Like the
      neighbouring MS32 hotspot, the NID1 hotspot is associated with a minisatellite,
      suggesting that hotspots predispose DNA to tandem repetition. Unlike MS32,
      crossover resolution breakpoints in NID1 avoid the minisatellite, producing a
      cold spot within the hotspot. This avoidance may be related to the palindromic
      nature of the minisatellite interfering with the generation and/or processing of
      recombination intermediates. The NID1 hotspot also contains a single nucleotide
      polymorphism (SNP) close to the centre, which appears to directly influence the
      frequency of crossover initiation. Quantitative gene conversion assays show that
      this SNP affects the frequency of gene conversion and crossover to a very similar
      extent, providing evidence that conversions and crossovers are triggered by the
      same recombination initiating events. The recombination-suppressing allele is
      over-transmitted to recombinant progeny, and provides the most dramatic example
      to date of recombination-mediated meiotic drive, of a magnitude sufficient to
      virtually guarantee that the recombination suppressor will eventually replace the
      more active allele in human populations.

PMID- 15987699
TI  - Genetic dissection of Pax6 dosage requirements in the developing mouse eye.
AB  - Haploinsufficiency of the transcription factor Pax6/PAX6 has been implicated in a
      number of congenital eye disorders in humans and mice, such as aniridia and Small
      eye, which affect the development and function of the lens, cornea, anterior eye
      segment and neuroretina. However, the widespread distribution of Pax6/PAX6
      protein within the developing and adult eye preclude the identification and
      direct study of the ocular tissues affected by a reduction in Pax6/PAX6 dosage.
      Here, we employed Cre/loxP-mediated inactivation of a single Pax6 allele in
      either the lens/cornea or the distal optic cup to dissect the tissue-specific
      sensitivity to Pax6 haploinsufficiency. Exclusive inactivation of a single Pax6
      allele in the lens recapitulates the Small-eye lens and corneal defects, while
      only mildly affects iris morphology in a non-cell-autonomous fashion. Conversely,
      selective inactivation of a single Pax6 allele in the distal optic cup revealed
      primarily cell-autonomous dosage requirements for proper iris differentiation,
      with no affects on either lens or corneal morphology. Pax6 dosage within the
      distal optic cup is found here to influence the number of progenitors destined
      for the anterior ocular structures, the timing of iris muscle-cell
      differentiation and iris stroma development. Taken together, we genetically
      dissected the complex mouse Small-eye phenotype, thereby pinpointing the
      underlying Pax6/PAX6 haploinsufficiency to autonomous dosage requirements within
      the developing iris and lens/cornea tissues.

PMID- 15987700
TI  - Meta-analysis of genome scans of age-related macular degeneration.
AB  - A genetic contribution to the development of age-related macular degeneration
      (AMD) is well established. Several genome-wide linkage studies have identified a
      number of putative susceptibility loci for AMD but only a few of these regions
      have been replicated in independent studies. Here, we perform a meta-analysis of
      six AMD genome screens using the genome-scan meta-analysis method, which allows
      linkage results from several studies to be combined, providing greater power to
      identify regions that show only weak evidence for linkage in individual studies.
      Results from non-parametric analysis for a broad AMD clinical phenotype
      (including two studies with quantitative traits) were extracted. For each study,
      120 genomic bins of approximately 30 cM were defined and ranked according to
      maximum evidence for linkage within each bin. Bin ranks were weighted according
      to study size and summed across all studies; the summed rank (SR) for each bin
      was assessed empirically for significance using permutation methods. A high SR
      indicates a region with consistent evidence for linkage across studies. The
      strongest evidence for an AMD susceptibility locus was found on chromosome 10q26
      where genome-wide significant linkage was observed (P=0.00025). Several other
      regions met the empirical significance criteria for bins likely to contain linked
      loci including adjacent pairs of bins on chromosomes 1q, 2p, 3p and 16. Several
      of the regions identified here showed only weak evidence for linkage in the
      individual studies. These results will help prioritize regions for future
      positional and functional candidate gene studies in AMD.

PMID- 15987701
TI  - The prion gene is associated with human long-term memory.
AB  - Human cognitive processes are highly variable across individuals and are
      influenced by both genetic and environmental factors. Although genetic variations
      affect short-term memory in humans, it is unknown whether genetic variability has
      also an impact on long-term memory. Because prion-like conformational changes may
      be involved in the induction of long-lasting synaptic plasticity, we examined the
      impact of single-nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP)
      on long-term memory in healthy young humans. SNPs in the genomic region of PRNP
      were associated with better long-term memory performance in two independent
      populations with different educational background. Among the examined PRNP SNPs,
      the common Met129Val polymorphism yielded the highest effect size. Twenty-four
      hours after a word list-learning task, carriers of either the 129MM or the 129MV
      genotype recalled 17% more information than 129VV carriers, but short-term memory
      was unaffected. These results suggest a role for the prion protein in the
      formation of long-term memory in humans.

PMID- 15987702
TI  - Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in
      tumours which result from germline FH and SDH mutations.
AB  - The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate
      dehydrogenase (SDHB, -C and -D), act as tumour suppressors. Germline mutations in
      FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas
      mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL). In this
      study, we have shown that FH-deficient cells and tumours accumulate fumarate and,
      to a lesser extent, succinate. SDH-deficient tumours principally accumulate
      succinate. In situ analyses showed that these tumours also have over-expression
      of hypoxia-inducible factor 1alpha (HIF1alpha), activation of HIF1alphatargets
      (such as vascular endothelial growth factor) and high microvessel density. We
      found no evidence of increased reactive oxygen species in our cells. Our data
      provide in vivo evidence to support the hypothesis that increased succinate
      and/or fumarate causes stabilization of HIF1alpha a plausible mechanism,
      inhibition of HIF prolyl hydroxylases, has previously been suggested by in vitro
      studies. The basic mechanism of tumorigenesis in HPGL and HLRCC is likely to be
      pseudo-hypoxic drive, just as it is in von Hippel-Lindau syndrome.

PMID- 15987703
TI  - LKB1 interacts with and phosphorylates PTEN: a functional link between two
      proteins involved in cancer predisposing syndromes.
AB  - Germline mutations of the LKB1 (STK11) tumor suppressor gene lead to Peutz
      Jeghers syndrome (PJS) and predisposition to cancer. LKB1 encodes a
      serine/threonine kinase generally inactivated in PJS patients. We identified the
      dual phosphatase and tumor suppressor protein PTEN as an LKB1-interacting
      protein. Several LKB1 point mutations associated with PJS disrupt the interaction
      with PTEN suggesting that the loss of this interaction might contribute to PJS.
      Although PTEN and LKB1 are predominantly cytoplasmic and nuclear, respectively,
      their interaction leads to a cytoplasmic relocalization of LKB1. In addition, we
      show that PTEN is a substrate of the kinase LKB1 in vitro. As PTEN is a dual
      phosphatase mutated in autosomal inherited disorders with phenotypes similar to
      those of PJS (Bannayan-Riley-Ruvalcaba syndrome and Cowden disease), our study
      suggests a functional link between the proteins involved in different
      hamartomatous polyposis syndromes and emphasizes the central role played by LKB1
      as a tumor suppressor in the small intestine.

PMID- 15987705
TI  - Complete myocardial revascularization: between myth and reality.

PMID- 15987704
TI  - Risk of cancer after low doses of ionising radiation: retrospective cohort study
      in 15 countries.
AB  - OBJECTIVES: To provide direct estimates of risk of cancer after protracted low
      doses of ionising radiation and to strengthen the scientific basis of radiation
      protection standards for environmental, occupational, and medical diagnostic
      exposures. DESIGN: Multinational retrospective cohort study of cancer mortality.
      SETTING: Cohorts of workers in the nuclear industry in 15 countries.
      PARTICIPANTS: 407 391 workers individually monitored for external radiation with
      a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS:
      Estimates of excess relative risks per sievert (Sv) of radiation dose for
      mortality from cancers other than leukaemia and from leukaemia excluding chronic
      lymphocytic leukaemia, the main causes of death considered by radiation
      protection authorities. RESULTS: The excess relative risk for cancers other than
      leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of
      causes of death related or unrelated to smoking indicate that, although
      confounding by smoking may be present, it is unlikely to explain all of this
      increased risk. The excess relative risk for leukaemia excluding chronic
      lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these
      estimates, 1-2% of deaths from cancer among workers in this cohort may be
      attributable to radiation. CONCLUSIONS: These estimates, from the largest study
      of nuclear workers ever conducted, are higher than, but statistically compatible
      with, the risk estimates used for current radiation protection standards. The
      results suggest that there is a small excess risk of cancer, even at the low
      doses and dose rates typically received by nuclear workers in this study.

PMID- 15987706
TI  - Extent of ST-segment depression and cardiac events in non-ST-segment elevation
      acute coronary syndromes.
AB  - AIMS: We sought to determine whether the extent of myocardial ischaemia on the
      admission electrocardiogram (ECG) has independent predictive value for short-term
      risk stratification of patients with non-ST-segment elevation acute coronary
      syndromes (NSTE ACS). Although the presence of ischaemic ECG changes on admission
      has been shown to predict outcome, the relationship between the extent of ECG
      changes and the risk of cardiac events is still ill defined. METHODS AND RESULTS:
      We analysed the admission ECGs of 5192 ACS patients enrolled in the GUSTO-IIb
      trial, without an ECG indication for thrombolysis. ECG tracings showing one or
      more of the following were eligible: ST-segment depression >0.5 mm, T-wave
      inversion >1 mm, and ST-segment elevation >0.5 mm but <1 mm. ECG variables
      associated with unfavourable 30 day outcomes in a univariable analysis were
      further assessed in a multivariable logistic regression model including
      independent clinical predictors. In the multivariable clinical, enzymatic, and
      ECG model, the sum of ST-segment depression (in millimetres) in all leads was a
      powerful independent predictor of 30 day death (P<0.0001), with a continuous
      increase in risk with the extent of ST-segment depression. The sum of ST-segment
      depression (P<0.0001) and the presence of minimal inferior ST-segment elevation
      (P<0.0001) or anterior ST-segment elevation (P=0.0182) were also independent
      predictors of the composite of death and myocardial infarction or reinfarction.
      The extent of ST-segment depression showed a highly significant correlation with
      the prevalence of three-vessel (P<0.0001) or left main coronary disease
      (P<0.0001), and also with the peak levels of creatine kinase (P<0.0001) during
      the index episode of ACS. CONCLUSION: In patients with NSTE ACS, the sum of ST
      segment depression in all ECG leads is a powerful predictor of all-cause
      mortality at 30 days, independent of clinical variables and correlates with the
      extent and severity of coronary artery disease. The presence of even minimal (<1
      mm) ST-segment elevation in anterior or inferior leads is independently
      associated with adverse outcomes.

PMID- 15987707
TI  - Effect of exercise training on plasma levels of C-reactive protein in healthy
      adults: the HERITAGE Family Study.
AB  - AIMS: To study the effect of exercise training on plasma C-reactive protein, a
      marker of inflammation. METHODS AND RESULTS: We performed a 20 week standardized
      exercise training programme in 652 sedentary healthy white and black men and
      women. C-reactive protein was measured with a high sensitivity assay. The study
      sample was stratified according to baseline C-reactive protein levels using a
      recommended classification (low <1.0 mg/L, n=265; moderate 1.0-3.0 mg/L, n=225;
      high >3.0 mg/L, n=162). The median C-reactive protein reduction was 1.34 mg/L in
      the high baseline C-reactive protein group. C-reactive protein levels did not
      change in the low or moderate baseline C-reactive protein groups. The difference
      among the C-reactive protein groups was significant adjusting for all correlates
      of baseline C-reactive protein (P<0.001) and additionally for changes in body
      weight, glucose, insulin, LDL cholesterol, HDL cholesterol, triglycerides,
      systolic and diastolic blood pressure, and maximal oxygen uptake (P<0.001). The C
      reactive protein reduction in the high baseline C-reactive protein group was
      consistent across all population groups (P<0.001 for difference among baseline C
      reactive protein groups). CONCLUSION: Plasma C-reactive protein levels are
      reduced in response to exercise training in sedentary healthy adults with high
      initial C-reactive protein levels. This finding may partly explain the
      effectiveness of regular physical activity in the prevention and treatment of
      cardiovascular and metabolic diseases.

PMID- 15987708
TI  - Two basic questions usually neglected: the definition of the technical parameters
      and contrast injection.

PMID- 15987709
TI  - Rapid and complete coronary arterial tree visualization with magnetic resonance
      imaging: feasibility and diagnostic performance.
AB  - AIMS: Current imaging of the coronary arteries with magnetic resonance coronary
      angiography (MRCA) is restricted to limited coverage of the coronary arterial
      tree and requires complex planning. We present and evaluate a rapid, single-scan
      MRCA approach with complete coverage of the coronary arterial tree. METHODS AND
      RESULTS: Fifty-five consecutive patients with suspected coronary artery disease
      underwent free-breathing, navigator-gated MRCA using a single three-dimensional
      volume with transversal slice orientation and nearly isotropic spatial resolution
      (1.2 x 1.2 x 1.4 mm(3)) with coverage of the whole heart [steady-state free
      precession (SSFP); TR/TE/flip angle: 5.3 ms/2.6 ms/90 degrees ; Philips Intera CV
      1.5T]. The acquisition duration per heart beat was individually adapted to the
      cardiac rest period. Correction of respiratory motion was done using a patient
      specific affine prospective navigator technique (two navigator beams: cranio
      caudal position on the dome of the right hemidiaphragm and anterior-posterior
      position on the right chest wall; gating window 10 mm). The diagnostic
      performance of MRCA in detecting significant coronary stenoses was evaluated
      against X-ray angiography as the standard of reference (32 patients) using a 16
      segment model. Effective scan duration was 18+/-6 min (navigator efficiency: 68+/
      14%). In all examinations, the main epicardial vessels [left anterior descending
      artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)],
      including their distal segments and major side branches (number of visible side
      branches: LAD, 2.0+/-0.9; LCX, 1.5+/-0.6; RCA, 2.3+/-0.9), were reliably
      visualized. Eighty-three per cent of all coronary segments were evaluable;
      sensitivity, specificity, and diagnostic accuracy were 78, 91, and 89%,
      respectively. CONCLUSION: The combination of an imaging sequence with an
      intrinsically high contrast (SSFP) and a sophisticated navigator technique
      (affine transformation) resulted in high quality, high resolution imaging of the
      whole coronary arterial tree within a short examination duration. Robustness and
      diagnostic accuracy may allow for a routine application in the near future.

PMID- 15987710
TI  - Blunted erythropoietin production and defective iron supply for erythropoiesis as
      major causes of anaemia in patients with chronic heart failure.
AB  - AIMS: Anaemia is often observed in patients with chronic heart failure (CHF), and
      it may be associated with a worse prognosis. Aim of this study was to identify
      the individual mechanisms of anaemia in CHF patients. METHODS AND RESULTS: One
      hundred and forty-eight consecutive patients with haemoglobin concentration <13
      g/dL (if males) or <12 g/dL (if females) were enrolled. Factors responsible for
      anaemia were investigated by evaluating endogenous erythropoietin (Epo)
      production, serum cytokines levels, body iron status, and iron supply for
      erythropoiesis. Most patients (57%) presented anaemia of chronic disease and
      among them, 92% showed evidence of a defective endogenous Epo production. This
      was indicated by an observed/predicted log(serum Epo) ratio less than 0.8 and/or
      a defective iron supply for erythropoiesis diagnosed by low transferrin
      saturation and/or increased value of soluble transferrin receptor. According to
      regression analysis sex, renal failure, and serum Epo were correlated with
      anaemia. CONCLUSION: According to our study, about half of anaemic CHF patients
      showed anaemia of chronic disease with blunted endogenous Epo production and/or a
      defective iron supply for erythropoiesis. Determination of the individual
      mechanisms of anaemia in CHF could justify a rational therapeutic approach to
      anaemia.

PMID- 15987711
TI  - Expression and function of inducible costimulator on peripheral blood T cells in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the role of inducible costimulator (ICOS) in the
      pathogenesis of SLE, we assessed its expression on peripheral blood CD4 and CD8 T
      cells and functional roles in patients with systemic lupus erythematosus (SLE).
      METHODS: Expression of ICOS on peripheral blood CD4 and CD8 T cells and ICOS
      ligand (ICOSL) on peripheral blood CD19 B cells from patients with SLE, patients
      with rheumatoid arthritis (RA) and healthy volunteers were determined by two
      colour flow cytometry. The functional costimulatory effects of ICOS on peripheral
      blood mononuclear cells (PBMC) were assessed by T-cell proliferative responses,
      cytokines, anti-double-stranded DNA (anti-dsDNA) antibody and total IgG
      production. RESULTS: Peripheral blood CD4 and CD8 T cells expressing ICOS were
      significantly increased in patients with SLE compared with patients with RA and
      healthy subjects. Peripheral blood CD19 B cells expressing ICOSL in SLE were
      markedly reduced compared with RA. Proliferative responses of anti-CD3/ICOS
      costimulation were significantly higher than those of anti-CD3/hamster IgG (HIgG)
      in healthy subjects, but not in patients with SLE. Anti-CD3/ICOS-stimulated SLE
      PBMC secreted similar levels of IL-10 and IFN-gamma but a significantly lower
      level of IL-2 than healthy PBMC. Anti-CD3/ICOS-mediated costimulation
      significantly enhanced the production of anti-dsDNA antibodies and total IgG in
      patients with SLE. CONCLUSION: Hyperexpression of ICOS on peripheral blood CD4
      and CD8 T cells from patients with SLE contributed to the dysregulated T-cell
      proliferation, T-cell activation and pathogenic autoantibody production, which
      showed that the abnormality of ICOS costimulation may play an immunopathological
      role(s) in the pathogenesis of SLE.

PMID- 15987712
TI  - Antiphospholipid antibodies are associated with enhanced oxidative stress,
      decreased plasma nitric oxide and paraoxonase activity in an experimental mouse
      model.
AB  - OBJECTIVE: Oxidative stress contributes to atherosclerosis, and evidence of
      enhanced oxidative stress exists in antiphospholipid syndrome (APS). In a non
      lupus murine model, we evaluated whether anticardiolipin (aCL) antibodies could
      affect the oxidant/antioxidant balance as an early biochemical step of APS.
      METHODS: Hybridomas producing human and murine aCL and anti-beta(2)-glycoprotein
      I (abeta2-GPI) monoclonal antibodies were injected into three groups of five
      female BALB/c severe combined immunodeficiency (SCID) mice. Corresponding
      hybridomas secreting non-antiphospholipid antibodies of the same isotype were
      employed as controls. Sera and organs were collected after 30 days. Paraoxonase
      (PON) activity, peroxynitrite, superoxide, nitric oxide (NO) and nitrotyrosine
      were measured in plasma. Expression of endothelial nitric oxide synthase and
      inducible nitric oxide synthase (iNOS) was assessed by western blot and
      immunohistochemistry. RESULTS: PON activity and NO (sum of nitrate and nitrite)
      levels were reduced in the human aCL IgG group (P<0.002 and P<0.04,
      respectively), whilst peroxynitrite and superoxide and expression of total
      antioxidant capacity of plasma were increased (P<0.01). PON and NO were decreased
      in the murine abeta2-GPI IgG and IgM aCL groups (P<0.03 and P<0.05,
      respectively). Nitrotyrosine was elevated in the human aCL IgG group (P<0.03).
      Western blotting showed reduced iNOS expression in the hearts of the IgG aCL
      group, confirmed by immunostaining. PON inversely correlated with IgG aCL titres
      (P<0.001), superoxide (P<0.008) and peroxynitrite levels (P<0.0009).
      Peroxynitrite and total IgG aCL were independent predictors of PON (P<0.0009 and
      P<0.02, respectively). Superoxide was the only independent predictor of NO
      (P<0.008) and of nitrotyrosine (P<0.002). CONCLUSION: aCL antibodies are
      associated with the decreased PON activity and reduced NO that may occur in the
      preclinical phase of APS.

PMID- 15987713
TI  - Carcinogen exposure and gene promoter hypermethylation in bladder cancer.
AB  - Tobacco smoking, certain occupational exposures, and exposure to inorganic
      arsenic in drinking water have been associated with the occurrence of bladder
      cancer. However, in these tumors the exposure-associated pattern of somatic
      alterations in genes in the causal pathway for disease has been poorly
      characterized. In particular, the mechanism by which arsenic induces bladder
      cancer and the effects of lower environmental levels of exposure remain
      uncertain. Animal and in-vitro studies have suggested that arsenic and other
      exposures may act through epigenetic mechanisms. We, therefore, examined, in a
      population-based study of human bladder cancer, the relationship between
      epigenetic silencing of three tumor suppressor genes, p16(INK4A), RASSF1A and
      PRSS3, and exposure to both tobacco and arsenic in bladder cancer. Promoter
      methylation of each of these genes occurred in approximately 30% of bladder
      cancers, and both RASSF1A and PRSS3 promoter methylation were associated with
      advanced tumor stage (P<0.001 and P<0.04, respectively). Arsenic exposure,
      measured as toenail arsenic, was associated with RASSF1A (P<0.02) and PRSS3
      (P<0.1) but not p16INK4A promoter methylation, in models adjusted for stage and
      other factors. Cigarette smoking was associated with a >2-fold increased risk of
      promoter methylation of the p16INK4A gene only, with greater risk seen in
      patients with exposures more recent to disease diagnosis. These results, from
      human bladder tumors, add to the body of animal and in vitro evidence that
      suggests a role in epigenetic alterations for bladder carcinogens.

PMID- 15987715
TI  - 1alpha,25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via
      modulation of selective proteases.
AB  - Inhibition of invasion and metastasis has become a new approach for treatment of
      advanced prostate cancer in which secondary hormone therapy has failed.
      Accumulating evidence indicates that 1alpha,25-dihydroxyvitamin D3 (1,25-VD)
      suppresses prostate cancer progression by inhibition of tumor growth and
      metastasis. However, the detailed mechanisms underlying these effects remain to
      be determined. Here, we used the in vitro cell invasion assay to demonstrate that
      1,25-VD inhibits the invasive ability of human prostate cancer cell lines, LNCaP,
      PC-3 and DU 145. Three major groups of proteases, the matrix metalloproteinases
      (MMPs), the plasminogen activators (PAs) and the cathepsins (CPs), that are
      involved in tumor invasion were then examined for changes in activity and
      expression after 1,25-VD treatment. We found that 1,25-VD decreased MMP-9 and
      CPs, but not PAs activities, while it increased the activity of their
      counterparts, tissue inhibitors of metalloproteinase-1 (TIMP-1) and cathepsin
      inhibitors. Mechanistic studies showed that 1,25-VD did not suppress MMP-9
      expression at the transcriptional level, but reduced its mRNA stability. In
      addition, 1,25-VD increased AP-1 complexes binding to TIMP-1 promoter, which
      contributed to the enhancement of TIMP-1 activity, and thus resulted in
      inhibition of MMP activity and tumor invasion. These findings support the idea
      that vitamin D-based therapies might be beneficial in the management of advanced
      prostate cancer, especially among patients who have higher MMP-9 and CPs
      activities.

PMID- 15987716
TI  - Dietary grape-seed proanthocyanidin inhibition of ultraviolet B-induced immune
      suppression is associated with induction of IL-12.
AB  - We have shown previously that dietary grape seed proanthocyanidins (GSPs) inhibit
      UVB-induced photocarcinogenesis in mice. As UVB-induced immune suppression has
      been implicated in the development of skin cancer risk, we investigated whether
      dietary GSPs can modulate the effects of UVB on the immune system. We found that
      the UVB-induced (180 mJ/cm2) ear swelling response (inflammatory reaction) was
      significantly lower in mice fed with a GSP-supplemented (0.5 and 1.0%, w/w) diet
      than mice fed with the standard AIN76A diet. Dietary GSPs markedly inhibited UVB
      induced (180 mJ/cm2) suppression of contact hypersensitivity responses in a local
      model of immunosuppression but had only moderate inhibitory effect in a systemic
      model of immunosuppression. Dietary GSPs reduced the UVB-induced increase in
      immunosuppressive cytokine interleukin (IL)-10 in skin and draining lymph nodes
      compared with mice that did not receive GSPs. In contrast, GSPs enhanced the
      production of immunostimulatory cytokine IL-12 in the draining lymph nodes.
      Intraperitoneal injection of GSPs-fed mice with a neutralizing anti-IL-12
      antibody abrogated the protective effects of the GSPs against UVB-induced
      suppression of the contact hypersensitivity response. These data indicate for the
      first time that GSPs modulate UVB-induced immunosuppression and suggest that this
      may be one of the possible mechanisms by which they prevent photocarcinogenesis
      in mice.

PMID- 15987714
TI  - Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and
      risk of pancreatic cancer.
AB  - To test the hypothesis that genetic variation in the metabolism of tobacco
      carcinogens, such as aromatic amines (AA) and heterocyclic amines (HCA),
      contributes to pancreatic cancer, we have examined genetic polymorphisms of three
      key enzymes, i.e. cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 and 2
      (NAT1 and NAT2), in a hospital-based case-control study of 365 patients with
      pancreatic adenocarcinoma and 379 frequency-matched healthy controls. Genotypes
      were determined using PCR-restriction fragment length polymorphism (RFLP) and
      Taqman methods. Smoking information was collected by personal interview. Adjusted
      odds ratio (AOR) and 95% confidence interval (CI) was estimated by unconditional
      multivariate logistic regression analysis. We found that the NAT1 'rapid' alleles
      were associated with a 1.5-fold increased risk of pancreatic cancer (95% CI: 1.0
      2.1) with adjustment of potential confounders. This effect was more prominent
      among never smokers (AOR: 2.4, 95% CI: 1.4-4.3) and females (AOR: 1.8, 95% CI:
      1.0-3.1). Some genotypes were significantly associated with increased risk for
      pancreatic cancer among smokers, especially heavy smokers (<20 pack years). For
      example, heavy smokers with the CYP1A2*1D (T-2467delT) delT, CYP1A2*1F(A-163C) C
      allele, NAT1 'rapid' or NAT2 'slow' alleles had an AOR (95% CI) of 1.4 (0.7-2.3),
      1.9 (1.1-3.4), 3.0 (1.6-5.4) and 1.5 (0.8-2.6), respectively, compared with never
      smokers carrying the non-at-risk alleles. These effects were more prominent in
      females than in males. The corresponding AOR (95% CI) was 3.1 (1.0-8.0), 3.8 (1.5
      10.1), 4.5 (1.6-12.7) and 2.0 (0.8-5.1) for females versus 1.0 (0.4-1.9), 1.1
      (0.5-2.4), 2.1 (1.0-4.6) and 1.1 (0.5-2.6) for males. A significant synergistic
      effect of CYP1A2*1F C allele and NAT1"rapid" alleles on the risk for pancreatic
      cancer was also detected among never smokers (AOR: 2.9, 95% CI: 1.2-6.9) and
      among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms
      of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer.

PMID- 15987717
TI  - Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer
      susceptibility.
AB  - Gastric cancer remains a major cause of death in the developed countries, and a
      large percentage is still genetically unexplained. Because of their major role in
      cell survival, mutations in translation factors and altered expression of these
      genes have been associated with cancer development. Apart from its role in
      translation termination, the eukaryotic translation release factor 3 (eRF3) is
      involved in several critical cellular processes, such as cell cycle regulation,
      cytoskeleton organization and apoptosis. The aim of this study was to evaluate
      eRF3/GSPT1 gene as a potential genetic susceptibility associated locus for
      gastric cancer, analysing a stable GGC expansion in exon 1 encoding a polyglycine
      tract in the N-terminal domain of the protein. DNA was obtained from 139 patients
      with gastric cancer and from 100 individuals of a healthy control population. The
      GGC expansion was amplified by PCR and the number of repeats determined by
      genotyping in an automatic sequencer. There are five known alleles encoding from
      8 to 12 glycines. The most common allele encodes 10 glycines. The 12-Gly allele
      was detected exclusively in the cancer patients (allelic frequency = 5%).
      Regardless of the genotype, patients with the 12-Gly allele had a 20-fold
      increased risk for gastric cancer. We also detected a single-base alteration in
      the gene (G274T) although no correlation with cancer development has been found.
      Thus, our results show that the GGC expansion may have a potential role in
      regulating eRF3/GSPT1 expression and/or changing the protein function that can
      lead to gastric cancer development.

PMID- 15987718
TI  - Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation
      of death receptor 5 (DR5).
AB  - Curcumin exhibits anti-inflammatory and antitumor activities. Although its
      functional mechanism has not been elucidated so far, numerous studies have shown
      that curcumin induces apoptosis in cancer cells. In the present study, we show
      that subtoxic concentrations of curcumin sensitize human renal cancer cells to
      the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated
      apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not
      interrupted by Bcl-2 overexpression. We found that treatment with curcumin
      significantly induces death receptor 5 (DR5) expression both at its mRNA and
      protein levels, accompanying the generation of the reactive oxygen species (ROS).
      Not only the pretreatment with N-acetylcystine but also the ectopic expression of
      peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis
      induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5
      upregulation. Taken together, the present study demonstrates that curcumin
      enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.

PMID- 15987722
TI  - Re: "Why evidence for the fetal origins of adult disease might be a statistical
      artifact: the 'reversal paradox' for the relation between birth weight and blood
      pressure in later life".

PMID- 15987719
TI  - Cells with pathogenic biallelic mutations in the human MUTYH gene are defective
      in DNA damage binding and repair.
AB  - Inherited biallelic mutations in the human MUTYH gene are responsible for the
      recessive syndrome--adenomatous colorectal polyposis (MUTYH associated polyposis,
      MAP)--which significantly increases the risk of colorectal cancer (CRC).
      Defective MUTYH activity causes G:C to T:A transversions in tumour APC and other
      genes thereby altering genomic integrity. We report that of the four established
      cell lines, derived from patients with the MAP phenotype and containing biallelic
      MUTYH mutations, three contain altered expressions of MUTYH protein (MUTYH Y165C(
      /-), MUTYH 1103delC/G382D and MUTYH Y165C/G382D but not MUTYH G382D(-/-)), but
      that all four cell lines have wild type levels of MUTYH mRNA. Mutant MUTYH
      proteins in these four cell lines possess significantly lowered binding and
      cleavage activities with heteroduplex oligonucleotides containing A.8-oxoG and 8
      oxoA.G mispairs. Transfection of mitochondrial or nuclear MUTYH cDNAs partially
      correct altered MUTYH expression and activity in these defective cell lines.
      Finally, we surprisingly find that defective MUTYH may not alter cell survival
      after hydrogen peroxide and menadione treatments. The Y165C and 1103delC
      mutations significantly reduce MUTYH protein stability and thus repair activity,
      whereas the G382D mutation produces dysfunctional protein only suggesting
      different functional molecular mechanisms by which the MAP phenotype may
      contribute to the development of CRC.

PMID- 15987723
TI  - Body size changes in relation to postmenopausal breast cancer among women on Long
      Island, New York.
AB  - To examine effects of body size change on postmenopausal breast cancer, the
      authors conducted a population-based case-control study among 990 cases and 1,006
      controls participating in the Long Island Breast Cancer Study Project in 1996
      1997. Women who had gained more than 15 kg (33 pounds) since age 20 years were at
      a 1.6-fold increased risk of breast cancer (95% confidence interval (CI): 1.11,
      2.26) relative to their counterparts with stable (+/-3 kg) weight. Subjects who
      had gained more than 11 kg (24 pounds) during the peri- and postmenopausal years
      (since age 50 years) had 1.62 times the risk of breast cancer of those whose
      weight remained unchanged during this time period. This effect of peri- and
      postmenopausal body size gain was present only among never users of hormone
      replacement therapy (odds ratio (OR) = 2.02 (95% CI: 1.35, 3.02) as opposed to
      0.81 (95% CI: 0.43, 1.53) for ever users; multiplicative interaction: p < 0.01)
      and was more pronounced among women with estrogen receptor-positive/progesterone
      receptor-positive breast cancer (OR = 2.17, 95% CI: 1.38, 3.42). Weight loss over
      the lifetime was associated with decreased risk of postmenopausal breast cancer
      (OR = 0.55, 95% CI: 0.32, 0.96). These results add to the literature by focusing
      on the perimenopausal weight trajectory and support efforts urging women to avoid
      weight gain as they age.

PMID- 15987724
TI  - Cancer mortality among US men and women with asthma and hay fever.
AB  - The relation between self-reported physician-diagnosed asthma and/or hay fever
      and cancer mortality was explored in a prospective cohort study of 1,102,247 US
      men and women who were cancer-free at baseline. During 18 years of follow-up,
      from 1982 to 2000, there were 81,114 cancer deaths. Cox proportional hazards
      models were used to obtain adjusted relative risks for all cancer mortality and
      for cancer mortality at 12 sites associated with allergy indicators. There were
      significant inverse associations between a history of both asthma and hay fever
      and overall cancer mortality (relative risk (RR) = 0.88, 95% confidence interval
      (CI): 0.83, 0.93) and colorectal cancer mortality (RR = 0.76, 95% CI: 0.64, 0.91)
      in comparison with persons with neither of these allergic conditions. A history
      of hay fever only was associated with a significantly lowered risk of pancreatic
      cancer mortality, and a history of asthma only was associated with a
      significantly lowered risk of leukemia mortality. In never smokers, these
      associations persisted but were no longer significant. Results for mortality from
      cancer at other sites were less consistent. Collectively, these results suggest
      an inverse association between a history of allergy and cancer mortality;
      however, the strength of evidence for this association is limited.

PMID- 15987725
TI  - Adjusting effect estimates for unmeasured confounding with validation data using
      propensity score calibration.
AB  - Often, data on important confounders are not available in cohort studies.
      Sensitivity analyses based on the relation of single, but not multiple,
      unmeasured confounders with an exposure of interest in a separate validation
      study have been proposed. In this paper, the authors controlled for measured
      confounding in the main cohort using propensity scores (PS's) and addressed
      unmeasured confounding by estimating two additional PS's in a validation study.
      The "error-prone" PS exclusively used information available in the main cohort.
      The "gold standard" PS additionally included data on covariates available only in
      the validation study. Based on these two PS's in the validation study, regression
      calibration was applied to adjust regression coefficients. This propensity score
      calibration (PSC) adjusts for unmeasured confounding in cohort studies with
      validation data under certain, usually untestable, assumptions. The authors used
      PSC to assess the relation between nonsteroidal antiinflammatory drugs (NSAIDs)
      and 1-year mortality in a large cohort of elderly persons. "Traditional"
      adjustment resulted in a hazard ratio for NSAID users of 0.80 (95% confidence
      interval (CI): 0.77, 0.83) as compared with an unadjusted hazard ratio of 0.68
      (95% CI: 0.66, 0.71). Application of PSC resulted in a more plausible hazard
      ratio of 1.06 (95% CI: 1.00, 1.12). Until the validity and limitations of PSC
      have been assessed in different settings, the method should be seen as a
      sensitivity analysis.

PMID- 15987726
TI  - Re: "Association between reported alcohol intake and cognition: results from the
      Women's Health Initiative Memory Study".

PMID- 15987727
TI  - Relation between ambient air quality and selected birth defects, seven county
      study, Texas, 1997-2000.
AB  - A population-based case-control study investigated the association between
      maternal exposure to air pollutants, carbon monoxide, nitrogen dioxide, ozone,
      sulfur dioxide, and particulate matter <10 microm in aerodynamic diameter during
      weeks 3-8 of pregnancy and the risk of selected cardiac birth defects and oral
      clefts in livebirths and fetal deaths between 1997 and 2000 in seven Texas
      counties. Controls were frequency matched to cases on year of birth, vital
      status, and maternal county of residence at delivery. Stationary monitoring data
      were used to estimate air pollution exposure. Logistic regression models adjusted
      for covariates available in the vital record. When the highest quartile of
      exposure was compared with the lowest, the authors observed positive associations
      between carbon monoxide and tetralogy of Fallot (odds ratio = 2.04, 95%
      confidence interval: 1.26, 3.29), particulate matter <10 microm in aerodynamic
      diameter and isolated atrial septal defects (odds ratio = 2.27, 95% confidence
      interval: 1.43, 3.60), and sulfur dioxide and isolated ventricular septal defects
      (odds ratio = 2.16, 95% confidence interval: 1.51, 3.09). There were inverse
      associations between carbon monoxide and isolated atrial septal defects and
      between ozone and isolated ventricular septal defects. Evidence that air
      pollution exposure influences the risk of oral clefts was limited. Suggestive
      results support a previously reported finding of an association between ozone
      exposure and pulmonary artery and valve defects.

PMID- 15987728
TI  - Easy SAS calculations for risk or prevalence ratios and differences.

PMID- 15987729
TI  - When is baseline adjustment useful in analyses of change? An example with
      education and cognitive change.
AB  - In research on the determinants of change in health status, a crucial analytic
      decision is whether to adjust for baseline health status. In this paper, the
      authors examine the consequences of baseline adjustment, using for illustration
      the question of the effect of educational attainment on change in cognitive
      function in old age. With data from the US-based Assets and Health Dynamics Among
      the Oldest Old survey (n = 5,726; born before 1924), they show that adjustment
      for baseline cognitive test score substantially inflates regression coefficient
      estimates for the effect of schooling on change in cognitive test scores compared
      with models without baseline adjustment. To explain this finding, they consider
      various plausible assumptions about relations among variables. Each set of
      assumptions is represented by a causal diagram. The authors apply simple rules
      for assessing causal diagrams to demonstrate that, in many plausible situations,
      baseline adjustment induces a spurious statistical association between education
      and change in cognitive score. More generally, when exposures are associated with
      baseline health status, this bias can arise if change in health status preceded
      baseline assessment or if the dependent variable measurement is unreliable or
      unstable. In some cases, change-score analyses without baseline adjustment
      provide unbiased causal effect estimates when baseline-adjusted estimates are
      biased.

PMID- 15987730
TI  - Neighborhood contextual influences on depressive symptoms in the elderly.
AB  - To understand whether neighborhood contexts contribute to the onset or
      maintenance of mental health problems independently of individual characteristics
      requires the use of multilevel study designs and analytical strategies. This
      study used a multilevel analytical framework to examine the relation between
      neighborhood context and risk of depressive symptoms, using data from the New
      Haven component of the Established Populations for Epidemiologic Studies of the
      Elderly, a community-based sample of noninstitutionalized men and women aged 65
      years or older and living in the city of New Haven, Connecticut, in 1982.
      Neighborhoods were characterized by census-based characteristics and also by
      measures of the neighborhood service environment using data abstracted from the
      New Haven telephone book Yellow Pages. Living in a poor neighborhood was
      associated with higher levels of depressive symptoms in older adults, above and
      beyond individual vulnerabilities. In addition, the presence of more elderly
      people in the neighborhood was associated with better mental health among older
      adults. The authors found no evidence that access to services hypothesized to
      promote social engagement, to provide health services, or to affect the
      reputation of a neighborhood explained (i.e., mediated) neighborhood variations
      in depressive symptoms.

PMID- 15987731
TI  - Systematic review and meta-analysis of the association between {beta}2
      adrenoceptor polymorphisms and asthma: a HuGE review.
AB  - A number of studies have investigated two common polymorphisms in the beta(2)
      adrenoceptor gene, Arg/Gly16 and Gln/Glu27, in relation to asthma susceptibility.
      The authors performed a meta-analysis of each polymorphism, as well as haplotype
      analysis, for adult and pediatric populations separately, using published data,
      supplemented by additional data requested from the original authors. Individual
      analysis detected no effect of Arg/Gly16 in adults but did suggest a recessive
      protective effect of Gly16 for children, with an odds ratio of 0.71 (95%
      confidence interval (CI): 0.53, 0.96) compared with the other genotypes. Results
      for Gln/Glu27 in adults seem to indicate that heterozygotes are at decreased risk
      of asthma than either homozygote (odds ratio = 0.73, 95% CI: 0.62, 0.87),
      although the studies are heterogeneous; in children, the Glu/Glu genotype has a
      decreased risk of asthma (odds ratio = 0.60, 95% CI: 0.35, 0.99) compared with
      the other genotypes. Despite the proximity of these two polymorphic sites, the
      linkage disequilibrium coefficient of 0.41 was not high (p < 0.001). Haplotype
      analysis suggests that there may be an interaction between the two sites, with a
      lower risk of asthma associated with the Glu27 allele (compared with Gln27), and
      that this risk is modified by the allele at position 16.

PMID- 15987732
TI  - The association of body mass index and pancreatic cancer in residents of
      southeastern Michigan, 1996-1999.
AB  - Increased body mass index has emerged as a potential risk factor for pancreatic
      cancer. The authors examined whether the association between body mass index and
      pancreatic cancer was modified by gender, smoking, and diabetes in residents of
      southeastern Michigan, 1996-1999. A total of 231 patients with newly diagnosed
      adenocarcinoma of the exocrine pancreas were compared with 388 general population
      controls. In-person interviews were conducted to ascertain information on
      demographic and lifestyle factors. Unconditional logistic regression models
      estimated the association between body mass index and pancreatic cancer. Males'
      risk for pancreatic cancer significantly increased with increasing body mass
      index (p(trend) = 0.048), while no relation was found for women (p(trend) =
      0.37). Among nonsmokers, those in the highest category of body mass index were
      3.3 times (95% confidence interval: 1.2, 9.2) more likely to have pancreatic
      cancer compared with those with low body mass index. In contrast, no relation was
      found for smokers (p(trend) = 0.94). While body mass index was not associated
      with pancreatic cancer risk among insulin users (p(trend) = 0.11), a significant
      increase in risk was seen in non-insulin users (p(trend) = 0.039). This well
      designed, population-based study offered further evidence that increased body
      mass index is related to pancreatic cancer risk, especially for men and
      nonsmokers. In addition, body mass index may play a role in the etiology of
      pancreatic cancer even in the absence of diabetes.

PMID- 15987733
TI  - Angiotensin II induces apoptosis in vivo in skeletal, as well as cardiac, muscle
      of the rat.
AB  - Our previous work has established that angiotensin II is cardiotoxic. Here we
      sought to investigate whether skeletal muscle is similarly susceptible to damage.
      Male Wistar rats were either given a single subcutaneous injection of angiotensin
      II (range 1 microg kg-1 to 10 mg kg-1) or only the vehicle and killed 7 h later,
      or implanted with preconditioned osmotic pumps dispensing 1 mg kg-1 day-1
      angiotensin II and killed 9 or 18 h later. Apoptotic (caspase 3 positive)
      myocytes were counted on cryosections of the heart, soleus, tibialis anterior and
      diaphragm muscle. Single injections of 100 microg kg-1 to 10 mg kg-1 angiotensin
      II induced significant (P<0.05) myocyte apoptosis (per 10(4) viable myocytes) in
      the heart and this was heterogeneously distributed, peaking (5.7+/-0.6; P<0.05)
      at a point 6 mm from the apex, i.e. approximately three-quarters of the way
      towards the base. The slow-twitch soleus muscle was also damaged significantly
      (peak=2.6+/-0.4; P<0.05), while only the administration of 1 mg kg-1 induced
      significant (P<0.05) apoptosis in the fast-twitch tibialis anterior muscle
      (peak=1.2+/-0.3). Infusion of 1 mg kg-1 day-1 angiotensin II induced more myocyte
      apoptosis than a single bolus administration of the same dose, and in general
      there was a higher incidence of apoptosis in muscles harvested after 18 than
      after 9 h. Infusion of 1 mg kg-1 day-1 angiotensin II over 18 h induced
      significant (P<0.05) myocyte apoptosis in the heart (3.3+/-0.4), soleus (3.9+/
      1), tibialis anterior (5.9+/-0.4) and diaphragm (19.8+/-5.6) muscle. Depending on
      the muscle type, angiotensin II induces myocyte apoptosis in skeletal muscle to a
      similar or greater extent as in cardiac muscle, supporting the hypothesis that
      angiotensin II is generally toxic to all striated muscles.

PMID- 15987734
TI  - The terminal phase of cytokinesis in the Caenorhabditis elegans early embryo
      requires protein glycosylation.
AB  - RNA interference (RNAi) was used to characterize the requirement of protein
      glycosylation for cell membrane stability during cytokinesis in the early embryo.
      This screen targeted 13 enzymes or components of polypeptide sugar transferases
      that initiate either N-glycosylation or three different pathways of O
      glycosylation. RNAi of genes in the mucin-type and epidermal growth factor-fringe
      glycosylation pathways did not affect cytokinesis. However, embryos deficient in
      N-glycosylation exhibited a variable inability to complete cytokinesis. The most
      potent block in early embryonic cell division was obtained by RNAi of the
      polypeptide xylose transferase (ppXyl-T), which is required to initiate the
      proteoglycan modification pathway. Two generations of ppXyl-T RNAi-feeding
      treatment reduced the body size, mobility, brood size, and life span of adult
      animals. Embryos escaping ppXyl-T and Gal-T2 RNAi lethality develop to adulthood
      but have cytokinesis-deficient offspring, suggesting that glycosyltransferases in
      the proteoglycan pathway are maternal proteins in the early embryo. Gal-T2::GFP
      fusions and anti-Gal-T2 antibodies revealed a perinuclear staining pattern,
      consistent with the localization of the Golgi apparatus. RNAi in green
      fluorescent protein (GFP)-tagged strains to follow tubulin, PIE-1, and chromatin
      showed that deficient proteoglycan biosynthesis uncouples the stability of newly
      formed cell membranes from cytokinesis, whereas cleavage furrow initiation,
      mitotic spindle function, karyokinesis, and partitioning of intrinsic components
      are intact.

PMID- 15987735
TI  - Differential intranuclear organization of transcription factors Sp1 and Sp3.
AB  - Sp1 and Sp3 are ubiquitously expressed mammalian transcription factors that
      activate or repress the expression of a variety of genes and are thought to
      compete for the same DNA binding site. We used indirect immunofluorescence
      microscopy and image deconvolution to show that Sp1 and Sp3 are organized into
      distinct nonoverlapping domains in human breast and ovarian cells. Domains of Sp1
      and Sp3 infrequently associate with sites of transcription. Sp3 partitions with
      the tightly bound nuclear protein fraction of hormone responsive MCF-7 breast
      cancer cells, whereas only a subpopulation of Sp1 is found in that fraction. Both
      Sp1 and Sp3 are bound to the nuclear matrix, and the nuclear matrix-associated
      sites of Sp1 and Sp3 are different. Indirect immunofluorescence studies
      demonstrate that Sp1 and Sp3 associate with histone deacetylases 1 and 2 and with
      the estrogen receptor alpha, albeit at low frequencies in MCF-7 cells. Chromatin
      immunoprecipitation (ChIP) and re-ChIP assays revealed that although both Sp1 and
      Sp3 bind to the estrogen-responsive trefoil factor 1 promoter in MCF-7 cells,
      they do not occupy the same promoter. Our results demonstrate the different
      features of Sp1 and Sp3, providing further evidence that Sp3 is not a functional
      equivalent of Sp1.

PMID- 15987736
TI  - The Salmonella effector PipB2 affects late endosome/lysosome distribution to
      mediate Sif extension.
AB  - After internalization into mammalian cells, the bacterial pathogen Salmonella
      enterica resides within a membrane-bound compartment, the Salmonella-containing
      vacuole (SCV). During its maturation process, the SCV interacts extensively with
      host cell endocytic compartments, especially late endosomes/lysosomes (LE/Lys) at
      later stages. These interactions are mediated by the activities of multiple
      bacterial and host cell proteins. Here, we show that the Salmonella type III
      effector PipB2 reorganizes LE/Lys compartments in mammalian cells. This activity
      results in the centrifugal extension of lysosomal glycoprotein-rich membrane
      tubules, known as Salmonella-induced filaments, away from the SCV along
      microtubules. Salmonella overexpressing pipB2 induce the peripheral accumulation
      of LE/Lys compartments, reducing the frequency of LE/Lys tubulation. Furthermore,
      ectopic expression of pipB2 redistributes LE/Lys, but not other cellular
      organelles, to the cell periphery. In coexpression studies, PipB2 can overcome
      the effects of dominant-active Rab7 or Rab34 on LE/Lys positioning. Deletion of a
      C-terminal pentapeptide motif of PipB2, LFNEF, prevents its peripheral targeting
      and effect on organelle positioning. The PipB2 homologue PipB does not possess
      this motif or the same biological activity as PipB2. Therefore, it seems that a
      divergence in the biological functions of these two effectors can be accounted
      for by sequence divergence in their C termini.

PMID- 15987737
TI  - Intermediate filaments interact with dormant ezrin in intestinal epithelial
      cells.
AB  - Ezrin connects the apical F-actin scaffold to membrane proteins in the apical
      brush border of intestinal epithelial cells. Yet, the mechanisms that recruit
      ezrin to the apical domain remain obscure. Using stable CACO-2 transfectants
      expressing keratin 8 (K8) antisense RNA under a tetracycline-responsive element,
      we showed that the actin-ezrin scaffold cannot assemble in the absence of
      intermediate filaments (IFs). Overexpression of ezrin partially rescued this
      phenotype. Overexpression of K8 in mice also disrupted the assembly of the brush
      border, but ezrin distributed away from the apical membrane in spots along
      supernumerary IFs. In cytochalasin D-treated cells ezrin localized to a subapical
      compartment and coimmunoprecipitated with IFs. Overexpression of ezrin in
      undifferentiated cells showed a Triton-insoluble ezrin compartment negative for
      phospho-T567 (dormant) ezrin visualized as spots along IFs. Pulse-chase analysis
      showed that Triton-insoluble, newly synthesized ezrin transiently
      coimmunoprecipitates with IFs during the first 30 min of the chase. Dormant, but
      not active (p-T567), ezrin bound in vitro to isolated denatured keratins in Far
      Western analysis and to native IFs in pull-down assays. We conclude that a
      transient association to IFs is an early step in the polarized assembly of apical
      ezrin in intestinal epithelial cells.

PMID- 15987738
TI  - Multiple myosin II heavy chain kinases: roles in filament assembly control and
      proper cytokinesis in Dictyostelium.
AB  - Myosin II filament assembly in Dictyostelium discoideum is regulated via
      phosphorylation of residues located in the carboxyl-terminal portion of the
      myosin II heavy chain (MHC) tail. A series of novel protein kinases in this
      system are capable of phosphorylating these residues in vitro, driving filament
      disassembly. Previous studies have demonstrated that at least three of these
      kinases (MHCK A, MHCK B, and MHCK C) display differential localization patterns
      in living cells. We have created a collection of single, double, and triple gene
      knockout cell lines for this family of kinases. Analysis of these lines reveals
      that three MHC kinases appear to represent the majority of cellular activity
      capable of driving myosin II filament disassembly, and reveals that cytokinesis
      defects increase with the number of kinases disrupted. Using biochemical
      fractionation of cytoskeletons and in vivo measurements via fluorescence recovery
      after photobleaching (FRAP), we find that myosin II overassembly increases
      incrementally in the mutants, with the MHCK A(-)/B(-)/C(-) triple mutant showing
      severe myosin II overassembly. These studies suggest that the full complement of
      MHC kinases that significantly contribute to growth phase and cytokinesis myosin
      II disassembly in this organism has now been identified.

PMID- 15987739
TI  - Role of the endocytic machinery in the sorting of lysosome-associated membrane
      proteins.
AB  - The limiting membrane of the lysosome contains a group of transmembrane
      glycoproteins named lysosome-associated membrane proteins (Lamps). These proteins
      are targeted to lysosomes by virtue of tyrosine-based sorting signals in their
      cytosolic tails. Four adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4,
      interact with such signals and are therefore candidates for mediating sorting of
      the Lamps to lysosomes. However, the role of these complexes and of the coat
      protein, clathrin, in sorting of the Lamps in vivo has either not been addressed
      or remains controversial. We have used RNA interference to show that AP-2 and
      clathrin-and to a lesser extent the other AP complexes-are required for efficient
      delivery of the Lamps to lysosomes. Because AP-2 is exclusively associated with
      plasma membrane clathrin coats, our observations imply that a significant
      population of Lamps traffic via the plasma membrane en route to lysosomes.

PMID- 15987740
TI  - Functions of the small proteins in the TOM complex of Neurospora crasssa.
AB  - The TOM (translocase of the outer mitochondrial membrane) complex of the outer
      mitochondrial membrane is required for the import of proteins into the organelle.
      The core TOM complex contains five proteins, including three small components
      Tom7, Tom6, and Tom5. We have created single and double mutants of all
      combinations of the three small Tom proteins of Neurospora crassa. Analysis of
      the mutants revealed that Tom6 plays a major role in TOM complex stability,
      whereas Tom7 has a lesser role. Mutants lacking both Tom6 and Tom7 have an
      extremely labile TOM complex and are the only class of mutant to exhibit an
      altered growth phenotype. Although single mutants lacking N. crassa Tom5 have no
      apparent TOM complex abnormalities, studies of double mutants lacking Tom5
      suggest that it also has a minor role in maintaining TOM complex stability. Our
      inability to isolate triple mutants supports the idea that the three proteins
      have overlapping functions. Mitochondria lacking either Tom6 or Tom7 are
      differentially affected in their ability to import different precursor proteins
      into the organelle, suggesting that they may play roles in the sorting of
      proteins to different mitochondrial subcompartments. Newly imported Tom40 was
      readily assembled into the TOM complex in mitochondria lacking any of the small
      Tom proteins.

PMID- 15987741
TI  - Transendothelial migration of melanoma cells involves N-cadherin-mediated
      adhesion and activation of the beta-catenin signaling pathway.
AB  - Cancer metastasis is a multistep process involving many types of cell-cell
      interactions, but little is known about the adhesive interactions and signaling
      events during extravasation of cancer cells. Transendothelial migration of cancer
      cells was investigated using an in vitro assay, in which melanoma cells were
      seeded on top of a monolayer of endothelial cells. Attachment of melanoma cells
      on the endothelium induced a twofold increase in N-cadherin expression in
      melanoma cells and the redistribution of N-cadherin to the heterotypic contacts.
      Transendothelial migration was inhibited when N-cadherin expression was repressed
      by antisense RNA, indicating a key role played by N-cadherin. Whereas N-cadherin
      and beta-catenin colocalized in the contact regions between melanoma cells and
      endothelial cells during the initial stages of attachment, beta-catenin
      disappeared from the heterotypic contacts during transmigration of melanoma
      cells. Immunolocalization and immunoprecipitation studies indicate that N
      cadherin became tyrosine-phosphorylated, resulting in the dissociation of beta
      catenin from these contact regions. Concomitantly, an increase in the nuclear
      level of beta-catenin occurred in melanoma cells, together with a sixfold
      increase in beta-catenin-dependent transcription. Transendothelial migration was
      compromised in cells expressing a dominant-negative form of beta-catenin, thus
      supporting a regulatory role of beta-catenin signaling in this process.

PMID- 15987742
TI  - Smad2 and Smad3 play different roles in rat hepatic stellate cell function and
      alpha-smooth muscle actin organization.
AB  - Hepatic stellate cells (HSC) play a central role in the pathogenesis of liver
      fibrosis, transdifferentiating in chronic liver disease from "quiescent" HSC to
      fibrogenic myofibroblasts. Transforming growth factor-beta (TGF-beta), acting
      both directly and indirectly, is a critical mediator of this process. To
      characterize the function of the TGF-beta signaling intermediates Smad2 and Smad3
      in HSC, we infected primary rat HSC in culture with adenoviruses expressing wild
      type and dominant negative Smads 2 and 3. Smad3-overexpressing cells exhibited
      increased deposition of fibronectin and type 1 collagen, increased chemotaxis,
      and decreased proliferation compared with uninfected cells and those infected
      with Smad2 or either dominant negative, demonstrating different biological
      functions for the two Smads. Additionally, coinfection experiments suggested that
      Smad2 and Smad3 signal via independent pathways. Smad3-overexpressing cells as
      well as TGF-beta-treated cells demonstrated more focal adhesions and increased
      alpha-smooth muscle actin (alpha-SMA) organization in stress fibers, although all
      cells reached the same level of alpha-SMA expression, indicating that Smad3 also
      regulates cytoskeletal organization in HSC. We suggest that TGF-beta, signaling
      via Smad3, plays an important role in the morphological and functional maturation
      of hepatic myofibroblasts.

PMID- 15987743
TI  - Involvement of PI3K and MAPK signaling in bcl-2-induced vascular endothelial
      growth factor expression in melanoma cells.
AB  - We have previously demonstrated that bcl-2 overexpression in tumor cells exposed
      to hypoxia increases the expression of vascular endothelial growth factor (VEGF)
      gene through the hypoxia-inducible factor-1 (HIF-1). In this article, we
      demonstrate that exposure of bcl-2 overexpressing melanoma cells to hypoxia
      induced phosphorylation of AKT and extracellular signal-regulated kinase (ERK)1/2
      proteins. On the contrary, no modulation of these pathways by bcl-2 was observed
      under normoxic conditions. When HIF-1alpha expression was reduced by RNA
      interference, AKT and ERK1/2 phosphorylation were still induced by bcl-2.
      Pharmacological inhibition of mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of
      VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia. No differences
      were observed between control and bcl-2-overexpressing cells in normoxia, in
      terms of VEGF protein secretion and in response to PI3K and MAPK inhibitors. We
      also demonstrated that RNA interference-mediated down-regulation of bcl-2
      expression resulted in a decrease in the ERK1/2 phosphorylation and VEGF
      secretion only in bcl-2-overexpressing cell exposed to hypoxia but not in control
      cells. In conclusion, our results indicate, for the first time, that bcl-2
      synergizes with hypoxia to promote expression of angiogenesis factors in melanoma
      cells through both PI3K- and MAPK-dependent pathways.

PMID- 15987745
TI  - Asymmetric dimethylarginine and kidney disease--marker or mediator?

PMID- 15987744
TI  - Localized RhoA activation as a requirement for the induction of membrane
      ruffling.
AB  - We examined the spatio-temporal activity of RhoA in migrating cells and growth
      factor-stimulated cells by using probes based on the principle of fluorescence
      resonance energy transfer. In HeLa cells migrating at a low cell density, RhoA
      was activated both at the contractile tail and at the leading edge. However, RhoA
      was activated only at the leading edge in MDCK cells migrating as a monolayer
      sheet. In growth factor-stimulated Cos1 and NIH3T3 cells, the activity of RhoA
      was greatly decreased at the plasma membrane, but remained high at the membrane
      ruffles in nascent lamellipodia. These observations are in agreement with the
      proposed role played by RhoA in stress fiber formation, but they also implicated
      RhoA in the regulation of membrane ruffling, the induction of which is a typical
      phenotype of activated Rac. In agreement with this view, dominant negative RhoA
      was found to inhibit membrane ruffling induced by active Rac. Furthermore, we
      found that Cdc42 activity was also required for high RhoA activity in membrane
      ruffles. Finally, we found that mDia1, but not ROCK, was stably associated with
      membrane ruffles. In conclusion, these results suggested that RhoA cooperates
      with Rac1 and Cdc42 to induce membrane ruffles via the recruitment of mDia.

PMID- 15987746
TI  - Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4
      activated transcription and profibrogenic effects of connective tissue growth
      factor.
AB  - Pentoxifylline (PTX) is a potent inhibitor of connective tissue growth factor
      (CTGF), but its underlying mechanism is poorly understood. Here, it was
      demonstrated that PTX inhibited not only TGF-beta1-induced CTGF expression but
      also CTGF-induced collagen I (alpha1) [Col I (alpha1)] expression in normal rat
      kidney fibroblasts (NRK-49F) and alpha-smooth muscle actin expression in normal
      rat kidney proximal tubular epithelial cells (NRK-52E). Furthermore, PTX
      attenuated tubulointerstitial fibrosis, myofibroblasts accumulation, and
      expression of CTGF and Col I (alpha1) in unilateral ureteral obstruction kidneys.
      The mechanism by which PTX reduced CTGF in NRK-49F and NRK-52E was investigated.
      Activation of Smad3/4 was essential for TGF-beta1-induced CTGF transcription, but
      PTX did not interfere with TGF-beta1 signaling to Smad2/3 activation and
      association with Smad4 and their nuclear translocation. However, PTX was capable
      of blocking activation of TGF-beta1-induced Smad3/4-dependent reporter as well as
      CTGF promoter, suggesting that PTX affects a factor that acts cooperatively with
      Smad3/4 to execute transcriptional activation. It was found that PTX increased
      intracellular cAMP and caused cAMP response element binding protein
      phosphorylation. The protein kinase A antagonist H89 abolished the inhibitory
      effect of PTX on Smad3/4-dependent CTGF transcription, whereas dibutyryl cAMP and
      forskolin recapitulated the inhibitory effect. In conclusion, these results
      indicate that PTX inhibits CTGF expression by interfering with Smad3/4-dependent
      CTGF transcription through protein kinase A and blocks the profibrogenic effects
      of CTGF on renal cells. Because of the dual blockade, PTX potently attenuates the
      tubulointerstitial fibrosis in unilateral ureteral obstruction kidneys.

PMID- 15987747
TI  - Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal
      disease.
AB  - The rise in the number of patients with HIV-associated nephropathy and HIV
      infection with end-stage renal disease (HIV+ ESRD) continues to be a substantial
      concern for the ESRD program. In order to assess the impact of highly active
      antiretroviral therapy (HAART) on the progression of patients with AIDS to the
      development of ESRD and to project the prevalence of HIV+ ESRD through 2020, a
      mathematical model of the dynamics of HIV+ infection in the ESRD population was
      developed. Epidemiologic data on AIDS and HIV+ ESRD among black individuals in
      the United States were obtained since 1991 from the Centers for Disease Control
      and Prevention and US Renal Data System, respectively. The model was constructed
      to predict the prevalence of HIV+ ESRD incorporating the current rate of growth
      in AIDS prevalence. Two possible trends were considered: linear AIDS growth and
      exponential AIDS growth. The likely effectiveness of HAART in slowing progression
      to HIV+ ESRD was estimated from the best fit of the model to the data after 1995,
      when HAART was introduced. The model was then used to evaluate recent data and to
      project the prevalence of HIV+ ESRD through 2020. The model suggested that HAART
      has reduced the rate of progression from AIDS to HIV+ ESRD by 38%. The model
      projected an increase in HIV+ ESRD prevalence in the future as a result of the
      increase in the AIDS population among black individuals. This increase was
      predicted even assuming a 95% reduction in the progression from AIDS to HIV+
      ESRD. Despite the potential benefit of HAART, the prevalence of HIV+ ESRD in the
      United States is expected to rise in the future as a result of the expansion of
      the AIDS population among black individuals. It is concluded that prevention of
      progression to ESRD should focus on early antiretroviral treatment of HIV
      infected patients who have evidence of HIV-associated nephropathy.

PMID- 15987748
TI  - Predictive factors of acute rejection after early cyclosporine withdrawal in
      renal transplant recipients who receive mycophenolate mofetil: results from a
      prospective, randomized trial.
AB  - The aim of this randomized, open-labeled trial was to compare the incidence of
      acute rejection after an early (3 mo posttransplantation) withdrawal of
      cyclosporine (CsA) or mycophenolate mofetil (MMF) in renal transplantation. Among
      218 eligible recipients, 108 nonsensitized, rejection-free patients who were
      under a triple drug regimen (CsA-MMF-prednisone) and had received a first kidney
      from a deceased donor were enrolled. At 3 mo after graft, they were gradually
      withdrawn from CsA (MMF group, n = 54) or MMF (CsA group, n = 54). A graft biopsy
      and a pharmacokinetic study of CsA and mycophenolic acid were systematically
      performed before the randomization. At 1 yr, graft and patient survival rates
      were 100% in each group. Renal function was improved in the MMF group compared
      with the CsA group (Cockcroft calculated clearance 64.7 +/- 18.7 versus 56.5 +/-
      18.0 ml/min; P = 0.023). However, the probability of acute rejection was higher
      in the MMF group (18.5 versus 5.6%; P = 0.045). The 10 patients who developed
      acute rejection after CsA withdrawal had a significantly higher incidence of
      borderline changes on the randomization biopsy than the 44 rejection-free
      patients (five of 10 versus eight of 44; P = 0.034), and they displayed a lower
      area under the curve of mycophenolic acid (43 +/- 9 versus 58 +/- 22 mg/h per L;
      P = 0.045). Multivariate analysis confirmed that borderline changes and area
      under the curve of mycophenolic acid were significant risk factors of acute
      rejection after CsA discontinuation. It is concluded that a systematic graft
      biopsy and a pharmacokinetic study of mycophenolic acid are needed to reduce the
      risk for acute rejection after CsA withdrawal.

PMID- 15987749
TI  - American Society of Pediatric Nephrology position paper on linking reimbursement
      to quality of care.

PMID- 15987750
TI  - Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside:
      role of p53 and Bcl-2-related family proteins.
AB  - Nephrotic-range proteinuria is due to glomerular diseases characterized by
      podocyte injury. Glucocorticoids are the standard of care for most forms of
      nephrotic syndrome. However, the precise mechanisms underlying the beneficial
      effects of glucocorticoids on podocytes, beyond its general immunosuppressive and
      anti-inflammatory effects, are still unknown. This study tested the hypothesis
      that the synthetic glucocorticoid dexamethasone directly reduces podocyte
      apoptosis. Growth-restricted immortalized mouse podocytes in culture were exposed
      to puromycin aminonucleoside (PA) to induce apoptosis. Our results showed that
      dexamethasone significantly reduced PA-induced apoptosis by 2.81-fold.
      Dexamethasone also rescued podocyte viability when exposed to PA. PA-induced
      apoptosis was associated with increased p53 expression, which was completely
      blocked by dexamethasone. Furthermore, the inhibition of p53 by the p53 inhibitor
      pifithrin-alpha protected against PA-induced apoptosis. Dexamethasone also
      lowered the increase in the proapoptotic Bax, which was increased by PA, and
      increased expression of the antiapoptotic Bcl-xL protein. Moreover, the decrease
      in p53 by dexamethasone was associated with increased Bcl-xL levels. Podocyte
      apoptosis induced by PA was caspase-3 independent but was associated with the
      translocation of apoptosis-inducing factor (AIF) from the cytoplasm to nuclei.
      AIF translocation was inhibited by dexamethasone. These results show that PA
      induced podocyte apoptosis is p53 dependent and associated with changes in Bcl-2
      related proteins and AIF translocation. The protective effects of dexamethasone
      on PA-induced apoptosis were associated with decreasing p53, increasing Bcl-xL,
      and inhibition of AIF translocation. These novel findings provide new insights
      into the beneficial effects of corticosteroids on podocytes directly, independent
      of its immunosuppressive effects.

PMID- 15987751
TI  - Permanent genetic tagging of podocytes: fate of injured podocytes in a mouse
      model of glomerular sclerosis.
AB  - Injured podocytes lose differentiation markers. Therefore, the true identity of
      severely injured podocytes remains unverified. A transgenic mouse model equipped
      with a podocyte-selective injury induction system was established. After
      induction of podocyte injury, mice rapidly developed glomerulosclerosis, with
      downregulation of podocyte marker proteins. Proliferating epithelial cells
      accumulated within Bowman's space, as seen in collapsing glomerulosclerosis. In
      this study, the fate of injured podocytes was pursued. Utilizing Cre-loxP
      recombination, the podocyte lineage was genetically labeled with lacZ in an
      irreversible manner. After podocyte injury, the number of lacZ-labeled cells,
      which were often negative for synaptopodin, progressively declined, correlating
      with glomerular damage. Parietal epithelial cells, but not lacZ-labeled
      podocytes, avidly proliferated. The cells proliferating within Bowman's capsule
      and, occasionally, on the outer surface of the glomerular basement membrane were
      lacZ-negative. Thus, when podocytes are severely injured, proliferating parietal
      epithelial cells migrate onto the visceral site, thereby mimicking proliferating
      podocytes.

PMID- 15987752
TI  - Role of p38 mitogen-activated protein kinase activation in podocyte injury and
      proteinuria in experimental nephrotic syndrome.
AB  - Podocytes play an important role in maintaining normal glomerular function and
      structure, and podocyte injury leads to proteinuria and glomerulosclerosis. The
      family of mitogen-activated protein kinases (MAPK; extracellular signal-regulated
      kinase [ERK], c-Jun N-terminal kinase, and p38) may be implicated in the
      progression of various glomerulopathies, but the role of MAPK in podocyte injury
      remains elusive. This study examined phosphorylation of p38 MAPK in clinical
      glomerulopathies with podocyte injury, as well as in rat puromycin
      aminonucleoside (PAN) nephropathy and mouse adriamycin (ADR) nephropathy. The
      effect of treatment with FR167653, an inhibitor of p38 MAPK, was also
      investigated in rodent models. In human podocyte injury diseases, the increased
      phosphorylation of p38 MAPK was observed at podocytes. In PAN and ADR
      nephropathy, the phosphorylation of p38 MAPK and ERK was marked but transient,
      preceding overt proteinuria. Pretreatment with FR167653 (day -2 to day 14,
      subcutaneously) to PAN or ADR nephropathy completely inhibited p38 MAPK
      activation and attenuated ERK phosphorylation, with complete suppression of
      proteinuria. Electron microscopy and immunohistochemistry for nephrin and
      connexin43 revealed that podocyte injury was markedly ameliorated by FR167653.
      Furthermore, early treatment with FR167653 effectively prevented
      glomerulosclerosis and renal dysfunction in the chronic phase of ADR nephropathy.
      In cultured podocytes, PAN or oxidative stress induced the phosphorylation of p38
      MAPK along with actin reorganization, and FR167653 inhibited such changes. These
      findings indicate that the activation of MAPK is necessary for podocyte injury,
      suggesting that p38 MAPK and, possibly, ERK should become a potential target for
      therapeutic intervention in proteinuric glomerulopathies.

PMID- 15987753
TI  - Engagement of transferrin receptor by polymeric IgA1: evidence for a positive
      feedback loop involving increased receptor expression and mesangial cell
      proliferation in IgA nephropathy.
AB  - IgA nephropathy (IgAN), the most common primary glomerulonephritis in the world,
      is characterized by IgA immune complex-mediated mesangial cell proliferation. The
      transferrin receptor (TfR) was identified previously as an IgA1 receptor, and it
      was found that, in biopsies of patients with IgAN, TfR is overexpressed and co
      localizes with IgA1 mesangial deposits. Here, it is shown that purified polymeric
      IgA1 (pIgA1) is a major inducer of TfR expression (three- to four-fold increase)
      in quiescent human mesangial cells (HMC). IgA-induced but not cytokine-induced
      HMC proliferation is dependent on TfR engagement as it is inhibited by both TfR1
      and TfR2 ectodomains as well as by the anti-TfR mAb A24. It is dependent on the
      continued presence of IgA1 rather than on soluble factors released during IgA1
      mediated activation. In addition, pIgA1-induced IL-6 and TGF-beta production from
      HMC was specifically inhibited by mAb A24, confirming that pIgA1 triggers a TfR
      dependent HMC activation. Finally, upregulation of TfR expression induced by sera
      from patients with IgAN but not from healthy individuals was dependent on IgA. It
      is proposed that deposited pIgA1 or IgA1 immune complexes could initiate a
      process of auto-amplification involving hyperexpression of TfR, allowing
      increased IgA1 mesangial deposition. Altogether, these data unveil a functional
      cooperation between pIgA1 and TfR for IgA1 deposition and HMC proliferation and
      activation, features that are commonly implicated in the chronicity of mesangial
      injuries observed in IgAN and that could explain the recurrence of IgA1 deposits
      in the mesangium after renal transplantation.

PMID- 15987754
TI  - Renal tubulointerstitial changes after internal irradiation with alpha-particle
      emitting actinium daughters.
AB  - The effect of external gamma irradiation on the kidneys is well described.
      However, the mechanisms of radiation nephropathy as a consequence of targeted
      radionuclide therapies are poorly understood. The functional and morphologic
      changes were studied chronologically (from 10 to 40 wk) in mouse kidneys after
      injection with an actinium-225 (225Ac) nanogenerator, a molecular-sized, antibody
      targeted, in vivo generator of alpha-particle-emitting elements. Renal
      irradiation from free, radioactive daughters of 225Ac led to time-dependent
      reduction in renal function manifesting as increase in blood urea nitrogen. The
      histopathologic changes corresponded with the decline in renal function.
      Glomerular, tubular, and endothelial cell nuclear pleomorphism and focal tubular
      cell injury, lysis, and karyorrhexis were observed as early as 10 wk. Progressive
      thinning of the cortex as a result of widespread tubulolysis, collapsed tubules,
      glomerular crowding, decrease in glomerular cellularity, interstitial
      inflammation, and an elevated juxtaglomerular cell count were noted at 20 to 30
      wk after treatment. By 35 to 40 wk, regeneration of simplified tubules with
      tubular atrophy and loss with focal, mild interstitial fibrosis had occurred. A
      lower juxtaglomerular cell count with focal cytoplasmic vacuolization, suggesting
      increased degranulation, was also observed in this period. A focal increase in
      tubular and interstitial cell TGF-beta1 expression starting at 20 wk, peaking at
      25 wk, and later declining in intensity with mild increase in the extracellular
      matrix deposition was noticed. These findings suggest that internally delivered
      alpha-particle irradiation-induced loss of tubular epithelial cells triggers a
      chain of adaptive changes that result in progressive renal parenchymal damage
      accompanied by a loss of renal function. These findings are dissimilar to those
      seen after gamma or beta irradiation of kidneys.

PMID- 15987755
TI  - Primed peripheral polymorphonuclear leukocyte: a culprit underlying chronic low
      grade inflammation and systemic oxidative stress in chronic kidney disease.
AB  - This study characterizes the causal relationship between peripheral
      polymorphonuclear leukocyte (PMNL) priming, systemic oxidative stress (OS), and
      inflammation in patients with varying degrees of renal insufficiency (chronic
      kidney disease [CKD] not on renal replacement therapy [RRT]: continuous
      ambulatory peritoneal dialysis or hemodialysis [HD]) and healthy control
      subjects. Rate of superoxide release was measured after stimulation of PMNL with
      phorbol 12-myristate 13-acetate or zymosan. Priming was estimated by the rate of
      superoxide release after phorbol 12-myristate 13-acetate stimulation. Systemic OS
      was related to PMNL priming and intracellular myeloperoxidase activity.
      Inflammation was linked to peripheral white blood cells and PMNL counts, PMNL
      apoptosis, and PMNL ex vivo survival in autologous and heterologous sera. PMNL
      priming and counts were related to the severity of renal failure in CKD not on
      RRT. Compared with control subjects, PMNL from all CKD patients showed increased
      priming, highest in HD, with a significant decrease in their response to zymosan.
      PMNL myeloperoxidase activity and apoptosis were increased in all renal failure
      patients. Decreased ex vivo cell survival and elevated leukocyte counts were
      found in all patients, highest in HD. Both PMNL priming and counts correlated
      negatively with the GFR. A positive significant correlation was shown between
      PMNL counts and their priming in all groups, suggesting that the increased PMNL
      count in peripheral blood is an adaptive response to PMNL priming. Hence, PMNL
      priming is a key mediator of low-grade inflammation and OS associated with renal
      failure, occurring before the onset of RRT and further augmented in chronic HD.

PMID- 15987756
TI  - Microalbuminuria and lower glomerular filtration rate at young adult age in
      subjects born very premature and after intrauterine growth retardation.
AB  - This prospective follow-up study of 422 19-yr-old subjects born very preterm in
      The Netherlands was performed to determine whether intrauterine growth
      retardation (IUGR) predisposes to abnormal GFR and microalbuminuria in
      adolescents. GFR (ml/min per 1.73 m2) was estimated using the Cockcroft-Gault
      equation, and albumin-creatinine ratio (mg/mmol) was calculated in a cohort of 19
      yr-old subjects born very preterm (gestational age <32 wk) in 1983. Birth weights
      were adjusted for gestational age and expressed as standard deviation scores
      (sds) as a measure of IUGR. All subjects had normal renal function. Birth weight
      (sds) was associated negatively with serum creatinine concentration (micromol/L)
      (beta = -1.0 micromol/L, 95% confidence interval [CI]: -1.9 to -0.2), positively
      with GFR (beta = 3.0, 95% CI: 1.7 to 4.2), and negatively with the logarithm of
      albumin-creatinine ratio (beta = -0.05, 95% CI: -0.09 to -0.01) in young adults
      born very preterm. IUGR is associated with unfavorable renal functions at young
      adult age in subjects born very premature. These data suggest that intrauterine
      growth-retarded subjects born very premature have an increased risk to develop
      progressive renal failure in later life.

PMID- 15987757
TI  - Transynaptic effects of tetanus neurotoxin in the oculomotor system.
AB  - The question whether general tetanus arises from the independent sum of multiple
      local tetani or results from the actions of the transynaptic tetanus neurotoxin
      (TeNT) in higher brain centres remains unresolved. Despite the blood-borne
      dissemination of TeNT from an infected wound, the access to the central nervous
      system is probably prevented by the blood-brain barrier. However, several long
      term sequelae (e.g. autonomic dysfunction, seizures, myoclonus, and sleep
      disturbances) present after the subsidence of muscle spasms might be indicative
      of central actions that occur farther away from lower motoneurons. Subsequently,
      the obvious entry route is the peripheral neurons followed by the transynaptic
      passage to the brain. We aimed at describing the pathophysiological correlates of
      TeNT translocation using the oculomotor system as a comprehensive model of cell
      connectivity and neuronal firing properties. In this study, we report that
      injection of TeNT into the medial rectus muscle of one eye resulted in bilateral
      gaze palsy attributed to firing alterations found in the contralaterally
      projecting abducens internuclear neurons. Functional alterations in the abducens
      to-oculomotor internuclear pathway resembled in part the classically described
      TeNT disinhibition. We confirmed the transynaptic targeted action of TeNT by
      analysing vesicle-associated membrane protein2 (VAMP2) immunoreactivity (the
      SNARE protein cleaved by TeNT). VAMP2 immunoreactivity decreased by 94.4% in the
      oculomotor nucleus (the first synaptic relay) and by 62.1% presynaptic to
      abducens neurons (the second synaptic relay). These results are the first
      demonstration of physiological changes in chains of connected neurons that are
      best explained by the transynaptic action of TeNT on premotor neurons as shown
      with VAMP2 immunoreactivity which serves as an indicator of TeNT activity.

PMID- 15987758
TI  - Spatial properties of central vestibular neurons of monkeys after bilateral
      lateral canal nerve section.
AB  - Thirty-seven neurons were recorded in the superior vestibular nucleus (SVN) of
      two cynomolgus monkeys 1-2 yr after bilateral lateral canal nerve section to test
      whether the central neurons had spatially adapted for the loss of lateral canal
      input. The absence of lateral canal function was verified with eye movement
      recordings. The relation of unit activity to the vertical canals was determined
      by oscillating the animals about a horizontal axis with the head in various
      orientations relative to the axis of rotation. Animals were also oscillated about
      a vertical axis while upright or tilted in pitch. In the second test, the
      vertical canals are maximally activated when the animals are tilted back about 
      50 degrees from the spatial upright and the lateral canals when the animals are
      tilted forward about 30 degrees . We reasoned that if central compensation
      occurred, the head orientation at which the response of the vertical canal
      related neurons was maximal should be shifted toward the plane of the lateral
      canals. No lateral canal-related units were found after nerve section, and
      vertical canal-related units were found only in SVN not in the rostral medial
      vestibular nucleus. SVN canal-related units were maximally activated when the
      head was tilted back at -47 +/- 17 and -50 +/- 12 degrees (means +/- SD) in the
      two animals, close to the predicted orientation of the vertical canals. This
      indicated that spatial adaptation of vertical canal-related vestibular neurons
      had not occurred. There were substantial neck and/or otolith-related inputs
      activating the vertical canal-related neurons in the nerve-sectioned animals,
      which could have contributed to oculomotor compensation after nerve section.

PMID- 15987759
TI  - Role of primate visual area V4 in the processing of 3-D shape characteristics
      defined by disparity.
AB  - We studied the responses of V4 neurons in awake, fixating monkeys to a diverse
      set of stereoscopic stimuli, including zero-order disparity (frontoparallel)
      stimuli, surfaces oriented in depth, and convex and concave shapes presented at
      various mean disparities. The responses of many V4 cells were significantly
      modulated across each of these stimulus subsets. In general, V4 cells were
      broadly tuned for zero-order disparity, and at any given disparity value, about
      four-fifths of the cells responded significantly above background. The response
      modulation by flat surfaces oriented in depth was significant for about one
      quarter of cells, and the responses of about one-third of the cells were
      significantly modulated by convex or concave surfaces at various mean
      disparities. However, we encountered no cells that unambiguously distinguished a
      given three-dimensional (3-D) shape independent of mean disparity. Thus 3-D
      shapes defined by disparity are unlikely to be represented explicitly at the
      level of individual V4 cells. Nonetheless, V4 cells likely play an important role
      in the processing of 3-D shape characteristics defined by disparity as a part of
      a distributed network.

PMID- 15987760
TI  - Dynamic spatiotemporal synaptic integration in cortical neurons: neuronal gain,
      revisited.
AB  - Gain modulation is a ubiquitous phenomenon in cortical neurons, providing
      flexibility to operate under changing conditions. The prevailing view is that
      this modulation reflects a change in the relationship between mean input and
      output firing rate brought about by variation in neuronal membrane
      characteristics. An alternative mechanism is proposed for neuronal gain
      modulation that takes into account the capability of cortical neurons to process
      spatiotemporal synaptic correlations. Through the use of numerical simulations,
      it is shown that voltage-gated and leak conductances, membrane potential, noise,
      and input firing rate modify the sensitivity of cortical neurons to the degree of
      temporal correlation between their synaptic inputs. These changes are expressed
      in a change of the temporal window for synaptic integration and the range of
      input correlation over which response probability is graded. The study also
      demonstrates that temporal integration depends on the distance between the inputs
      and that this interplay of space and time is modulated by voltage-gated and leak
      conductances. Thus, gain modulation may reflect a change in the relationship
      between spatiotemporal synaptic correlations and output firing probability. It is
      further proposed that by acting synergistically with the network, dynamic
      spatiotemporal synaptic integration in cortical neurons may serve a functional
      role in the formation of dynamic cell assemblies.

PMID- 15987761
TI  - Subtype-specific GABA transporter antagonists synergistically modulate phasic and
      tonic GABAA conductances in rat neocortex.
AB  - GABAergic inhibition in the brain can be classified as either phasic or tonic.
      gamma-Aminobutyric acid (GABA) uptake by GABA transporters (GATs) can limit the
      time course of phasic currents arising from endogenous and exogenous GABA, as
      well as decrease a tonically active GABA current. GABA transporter subtypes 1 and
      3 (GAT-1 and GAT-3) are the most heavily expressed of the four known GAT
      subtypes. The role of GATs in shaping GABA currents in the neocortex has not been
      explored. We obtained patch-clamp recordings from layer II/III pyramidal cells
      and layer I interneurons in rat sensorimotor cortex. We found that selective GAT
      1 inhibition with NO711 decreased the amplitude and increased the decay time of
      evoked inhibitory postsynaptic currents (IPSCs) but had no effect on the tonic
      current or spontaneous IPSCs (sIPSCs). GAT-2/3 inhibition with SNAP-5114 had no
      effect on IPSCs or the tonic current. Coapplication of NO711 and SNAP-5114
      substantially increased tonic currents and synergistically decreased IPSC
      amplitudes and increased IPSC decay times. sIPSCs were not resolvable with
      coapplication of NO711 and SNAP-5114. The effects of the nonselective GAT
      antagonist nipecotic acid were similar to those of NO711 and SNAP-5114 together.
      We conclude that synaptic GABA levels in neocortical neurons are controlled
      primarily by GAT-1, but that GAT-1 and GAT-2/3 work together extrasynaptically to
      limit tonic currents. Inhibition of any one GAT subtype does not increase the
      tonic current, presumably as a result of increased activity of the remaining
      transporters. Thus neocortical GAT-1 and GAT-2/3 have distinct but overlapping
      roles in modulating GABA conductances.

PMID- 15987762
TI  - Quantitative characterization of disparity tuning in ventral pathway area V4.
AB  - We performed a quantitative characterization of binocular disparity-tuning
      functions in the ventral (object-processing) pathway of the macaque visual
      cortex. We measured responses of 452 area V4 neurons to stimuli with disparities
      ranging from -1.0 to +1.0 degrees. Asymmetric Gaussian functions fit the raw data
      best (median R = 0.90), capturing both the modal components (local peaks in the 
      1.0 to +1.0 degrees range) and the monotonic components (linear or sigmoidal
      dependency on disparity) of the tuning patterns. Values derived from the
      asymmetric Gaussian fits were used to characterize neurons on a modal x monotonic
      tuning domain. Points along the modal tuning axis correspond to classic tuned
      excitatory and inhibitory patterns; points along the monotonic axis correspond to
      classic near and far patterns. The distribution on this domain was continuous,
      with the majority of neurons exhibiting a mixed modal/monotonic tuning pattern.
      The distribution in the modal dimension was shifted toward excitatory patterns,
      consistent with previous results in other areas. The distribution in the
      monotonic dimension was shifted toward tuning for crossed disparities
      (corresponding to stimuli nearer than the fixation plane). This could reflect a
      perceptual emphasis on objects or object parts closer to the observer. We also
      found that disparity-tuning strength was positively correlated with orientation
      tuning strength and color-tuning strength, and negatively correlated with
      receptive field eccentricity.

PMID- 15987763
TI  - Serotonin modulates axo-axonal coupling between neurons critical for learning in
      the leech.
AB  - S cells form a chain of electrically coupled neurons that extends the length of
      the leech CNS and plays a critical role in sensitization during whole-body
      shortening. This process requires serotonin, which acts in part by altering the
      pattern of activity in the S-cell network. Serotonin-containing axons and
      varicosities were observed in Faivre's nerve where the S-to-S-cell electrical
      synapses are located. To determine whether serotonin modulates these synapses, S
      cell action-potential (AP) propagation was studied in a two-ganglion chain
      containing one electrical synapse. Suction electrodes were placed on the cut ends
      of the connectives to stimulate one S cell while recording the other, coupled S
      cell's APs. A third electrode, placed en passant, recorded the APs near the
      electrical synapse before they propagated through it. Low concentrations of the
      gap junction inhibitor octanol increased AP latency across the two-ganglion
      chain, and this effect was localized to the region of axon containing the
      electrical synapse. At higher concentrations, APs failed to propagate across the
      synapse. Serotonin also increased AP latency across the electrical synapse,
      suggesting that serotonin reduced coupling between S cells. This effect was
      independent of the direction of propagation and increased with the number of
      electrical synapses in progressively longer chains. Furthermore, serotonin
      modulated instantaneous AP frequency when APs were initiated in separate S cells
      and in a computational model of S-cell activity after mechanosensory input. Thus
      serotonergic modulation of S-cell electrical synapses may contribute to changes
      in the pattern of activity in the S-cell network.

PMID- 15987764
TI  - Mechanisms underlying reorganization of fractured tactile cerebellar maps after
      deafferentation in developing and adult rats.
AB  - Our previous studies showed that fractured tactile cerebellar maps in rats
      reorganize after deafferentation during development and in adulthood while
      maintaining a fractured somatotopy. Several months after deafferentation of the
      infraorbital branch of the trigeminal nerve, the missing upper lip innervation is
      replaced in the tactile maps in the granule cell layer of crus IIa. The
      predominant input into the denervated area is always the upper incisor
      representation. This study examined whether this reorganization was caused by
      mechanisms intrinsic to the cerebellum or extrinsic, i.e., occurring in
      somatosensory structures afferent to the cerebellum. We first compared normal and
      deafferented maps and found that the expansion of the upper incisor is not caused
      by a preexisting bias in the strength or abundance of upper incisor input in
      normal animals. We then mapped tactile representations before and immediately
      after denervation. We found that the pattern of reorganization observed in the
      cerebellum several months later is not caused by unmasking of a silent or weaker
      upper incisor representation. Both results indicate that the reorganization is
      not a result of subsequent growth or sprouting mechanism within the cerebellum
      itself. Finally, we compared postlesion maps in the cerebellum and the
      somatosensory cortex. We found that the upper incisor representation
      significantly expands in both regions and that this expansion is correlated,
      suggesting that reorganization in the cerebellum is a passive consequence of
      reorganization in afferent cerebellar pathways. This result has important
      developmental and functional implications.

PMID- 15987765
TI  - Cluster analysis-based physiological classification and morphological properties
      of inhibitory neurons in layers 2-3 of monkey dorsolateral prefrontal cortex.
AB  - In primates, little is known about intrinsic electrophysiological properties of
      neocortical neurons and their morphological correlates. To classify inhibitory
      cells (interneurons) in layers 2-3 of monkey dorsolateral prefrontal cortex we
      used whole cell voltage recordings and intracellular labeling in slice
      preparation with subsequent morphological reconstructions. Regular spiking
      pyramidal cells have been also included in the sample. Neurons were successfully
      segregated into three physiological clusters: regular-, intermediate-, and fast
      spiking cells using cluster analysis as a multivariate exploratory technique.
      When morphological types of neurons were mapped on the physiological clusters,
      the cluster of regular spiking cells contained all pyramidal cells, whereas the
      intermediate- and fast-spiking clusters consisted exclusively of interneurons.
      The cluster of fast-spiking cells contained all of the chandelier cells and the
      majority of local, medium, and wide arbor (basket) interneurons. The cluster of
      intermediate spiking cells predominantly consisted of cells with the morphology
      of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a
      quantitative approach enabled us to demonstrate that intrinsic
      electrophysiological properties of neurons in the monkey prefrontal cortex define
      distinct cell types, which also display distinct morphologies.

PMID- 15987766
TI  - Characteristic membrane potential trajectories in primate sensorimotor cortex
      neurons recorded in vivo.
AB  - We examined the membrane potentials and firing properties of motor cortical
      neurons recorded intracellularly in awake, behaving primates. Three classes of
      neuron were distinguished by 1) the width of their spikes, 2) the shape of the
      afterhyperpolarization (AHP), and 3) the distribution of interspike intervals.
      Type I neurons had wide spikes, exhibited scoop-shaped AHPs, and fired
      irregularly. Type II neurons had narrower spikes, showed brief postspike
      afterdepolarizations before the AHP, and sometimes fired high-frequency doublets.
      Type III neurons had the narrowest spikes, showed a distinct post-AHP
      depolarization, or "rebound AHP" (rAHP), lasting nearly 30 ms, and tended to fire
      at 25-35 Hz. The evidence suggests that an intrinsic rAHP may confer on these
      neurons a tendency to fire at a preferred frequency governed by the duration of
      the rAHP and may contribute to a "pacemaking" role in generating cortical
      oscillations.

PMID- 15987767
TI  - Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of
      {beta}-cell ATP-sensitive potassium channels.
AB  - ATP-sensitive potassium (K(ATP)) channels of pancreatic beta-cells mediate
      glucose-induced insulin secretion by linking glucose metabolism to membrane
      excitability. The number of plasma membrane K(ATP) channels determines the
      sensitivity of beta-cells to glucose stimulation. The K(ATP) channel is formed in
      the endoplasmic reticulum (ER) on coassembly of four inwardly rectifying
      potassium channel Kir6.2 subunits and four sulfonylurea receptor 1 (SUR1)
      subunits. Little is known about the cellular events that govern the channel's
      biogenesis efficiency and expression. Recent studies have implicated the
      ubiquitin-proteasome pathway in modulating surface expression of several ion
      channels. In this work, we investigated whether the ubiquitin-proteasome pathway
      plays a role in the biogenesis efficiency and surface expression of K(ATP)
      channels. We provide evidence that, when expressed in COS cells, both Kir6.2 and
      SUR1 undergo ER-associated degradation via the ubiquitin-proteasome system.
      Moreover, treatment of cells with proteasome inhibitors MG132 or lactacystin
      leads to increased surface expression of K(ATP) channels by increasing the
      efficiency of channel biogenesis. Importantly, inhibition of proteasome function
      in a pancreatic beta-cell line, INS-1, that express endogenous K(ATP) channels
      also results in increased channel number at the cell surface, as assessed by
      surface biotinylation and whole cell patch-clamp recordings. Our results support
      a role of the ubiquitin-proteasome pathway in the biogenesis efficiency and
      surface expression of beta-cell K(ATP) channels.

PMID- 15987768
TI  - Notch-mediated CBF-1/RBP-J{kappa}-dependent regulation of human vascular smooth
      muscle cell phenotype in vitro.
AB  - Vascular smooth muscle cell (VSMC) phenotypic modulation is a key factor in
      vascular pathology. We have investigated the role of Notch receptor signaling in
      controlling human vascular smooth muscle cell (hVSMC) differentiation in vitro
      and established a role for cyclic strain-induced changes in Notch signaling in
      promoting this phenotypic response. The expression of alpha-actin, calponin,
      myosin, and smoothelin was examined by performing immunocytochemistry, Western
      blot analysis, and quantitative real-time PCR in hVSMCs cultured under static
      conditions after forced overexpression of constitutively active Notch 1 and 3
      receptors, inhibition of endogenous Cp-binding factor 1 (CBF-1)/recombination
      signal sequence-binding protein-Jkappa (RBP-Jkappa) signaling, and exposure to
      cyclic strain using a Flexercell Tension Plus unit. Overexpression of
      constitutively active Notch intracellular (IC) receptors (Notch 1 IC and Notch 3
      IC) resulted in a significant downregulation of alpha-actin, calponin, myosin,
      and smoothelin expression, an effect that was significantly attenuated after
      inhibition of Notch-mediated, CBF-1/RBP-Jkappa-dependent signaling by
      coexpression of RPMS-1 (Epstein-Barr virus-encoded gene product) and selective
      knockdown of basic helix-loop-helix factors [hairy enhancer of split (HES) gene
      and Hes-related transcription (Hrt) factors Hrt-1, Hrt-2, and Hrt-3] using
      targeted small interfering RNA. Cells cultured under conditions of defined
      equibiaxial cyclic strain (10% strain, 60 cycles/min, 24 h) exhibited a
      significant reduction in Notch 1 IC and Notch 3 IC expression concomitant with a
      significant increase in VSMC differentiation marker expression. Moreover, this
      cyclic strain-induced increase was further enhanced after inhibition of CBF-1/RBP
      Jkappa-dependent signaling with RPMS-1. These findings suggest that Notch
      promotes changes in hVSMC phenotype via activation of CBF-1/RBP-Jkappa-dependent
      pathways in vitro and contributes to the phenotypic response of VSMCs to cyclic
      strain-induced changes in VSMC differentiation.

PMID- 15987769
TI  - Expression of pro-Muclin in pancreatic AR42J cells induces functional regulated
      secretory granules.
AB  - It is not clear how protein cargo is sorted to and retained in forming regulated
      secretory granules (RSG). Here, the sulfated mucin-type glycoprotein pro-Muclin
      was tested for its ability to induce RSG in the poorly differentiated rat
      pancreatic cell line AR42J. AR42J cells express RSG content proteins, but they
      fail to make granules. Adenovirus-pro-Muclin-infected AR42J cells store amylase,
      accumulate RSG, and respond to hormonal stimulation by secreting the stored
      protein. Expression of pro-Muclin combined with the inducing effect of
      dexamethasone resulted in a significant enhancement of the efficiency of
      regulated secretion. The effect of pro-Muclin was a strong decrease in
      constitutive secretion compared with dexamethasone-induction alone. A pro-Muclin
      construct missing the cytosolic tail domain was less effective at improving the
      efficiency of regulated secretion compared with the full-length construct.
      Increased expression of cargo (using adenovirus amylase) also modestly enhanced
      regulated secretion, indicating that part of pro-Muclin's effect may be due to
      increased expression of cargo protein. Overall, the data show that pro-Muclin
      acts as a sorting receptor that can induce RSG, and that its cytosolic tail is
      important in this process.

PMID- 15987770
TI  - {Omega}-3 and {omega}-6 polyunsaturated fatty acids block HERG channels.
AB  - Dietary polyunsaturated fatty acids (PUFAs) have been reported to exhibit
      antiarrhythmic properties, which have been attributed to their availability to
      modulate Na(+), Ca(2+), and several K(+) channels. However, their effects on
      human ether-a-go-go-related gene (HERG) channels are unknown. In this study we
      have analyzed the effects of arachidonic acid (AA, omega-6) and docosahexaenoic
      acid (DHA, omega-3) on HERG channels stably expressed in Chinese hamster ovary
      cells by using the whole cell patch-clamp technique. At 10 microM, AA and DHA
      blocked HERG channels, at the end of 5-s pulses to -10 mV, to a similar extent
      (37.7 +/- 2.4% vs. 50.2 +/- 8.1%, n = 7-10, P > 0.05). 5,6,11,14
      Eicosatetrayenoic acid, a nonmetabolizable AA analog, induced effects similar to
      those of AA on HERG current. Both PUFAs shifted the midpoint of activation curves
      of HERG channels by -5.1 +/- 1.8 mV (n = 10, P < 0.05) and -11.2 +/- 1.1 mV (n =
      7, P < 0.01). Also, AA and DHA shifted the midpoint of inactivation curves by
      +12.0 +/- 3.9 mV (n = 4; P < 0.05) and +15.8 +/- 4.3 mV (n = 4; P < 0.05),
      respectively. DHA and AA accelerated the deactivation kinetics and slowed the
      inactivation kinetics at potentials positive to +40 mV. Block induced by DHA, but
      not that produced by AA, was higher when measured after applying a pulse to -120
      mV (I-->O). Finally, both AA and DHA induced a use-dependent inhibition of HERG
      channels. In summary, block induced by AA and DHA was time, voltage, and use
      dependent. The results obtained suggest that both PUFAs bind preferentially to
      the open state of the channel, although an interaction with inactivated HERG
      channels cannot be ruled out for AA.

PMID- 15987771
TI  - Modulation of tyramine signaling by osmolality in an insect secretory epithelium.
AB  - The control of water balance in multicellular organisms depends on absorptive and
      secretory processes across epithelia. This study concerns the effects of
      osmolality on the function of the Malpighian tubules (MTs), a major component of
      the insect excretory system. Previous work has shown that the biogenic amine
      tyramine increases transepithelial chloride conductance and urine secretion in
      Drosophila MTs. This study demonstrates that the response of MTs to tyramine, as
      measured by the depolarization of the transepithelial potential (TEP), is
      modulated by the osmolality of the surrounding medium. An increase in osmolality
      caused decreased tyramine sensitivity, whereas a decrease in osmolality resulted
      in increased tyramine sensitivity; changes in osmolality of +/-20% resulted in a
      nearly 10-fold modulation of the response to 10 nM tyramine. The activity of
      another diuretic agent, leucokinin, was similarly sensitive to osmolality,
      suggesting that the modulation occurs downstream of the tyramine receptor. In
      response to continuous tyramine signaling, as likely occurs in vivo, the TEP
      oscillates, and an increase in osmolality lengthened the period of these
      oscillations. Increased osmolality also caused a decrease in the rate of urine
      production; this decrease was attenuated by the tyraminergic antagonist
      yohimbine. A model is proposed in which this modulation of tyramine signaling
      enhances the conservation of body water during dehydration stress. The modulation
      of ligand signaling is a novel effect of osmolality and may be a widespread
      mechanism through which epithelia respond to changes in their environment.

PMID- 15987772
TI  - Hypoxia-inducible factor-dependent histone deacetylase activity determines stem
      cell fate in the placenta.
AB  - Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor composed
      of HIFalpha and the arylhydrocarbon receptor nuclear translocator
      (ARNT/HIF1beta). Previously, we have reported that ARNT function is required for
      murine placental development. Here, we used cultured trophoblast stem (TS) cells
      to investigate the molecular basis of this requirement. In vitro, wild-type TS
      cell differentiation is largely restricted to spongiotrophoblasts and giant
      cells. Interestingly, Arnt-null TS cells differentiated into chorionic
      trophoblasts and syncytiotrophoblasts, as demonstrated by their expression of
      Tfeb, glial cells missing 1 (Gcm1) and the HIV receptor CXCR4. During this
      process, a region of the differentiating Arnt-null TS cells underwent granzyme B
      mediated apoptosis, suggesting a role for this pathway in murine
      syncytiotrophoblast turnover. Surprisingly, HIF1alpha and HIF2alpha were induced
      during TS cell differentiation in 20% O2; additionally, pVHL levels were
      modulated during the same time period. These results suggest that oxygen
      independent HIF functions are crucial to this differentiation process. As histone
      deacetylase (HDAC) activity has been linked to HIF-dependent gene expression, we
      investigated whether ARNT deficiency affects this epigenetic regulator.
      Interestingly, Arnt-null TS cells had reduced HDAC activity, increased global
      histone acetylation, and altered class II HDAC subcellular localization. In wild
      type TS cells, inhibition of HDAC activity recapitulated the Arnt-null phenotype,
      suggesting that crosstalk between the HIFs and the HDACs is required for normal
      trophoblast differentiation. Thus, the HIFs play important roles in modulating
      the developmental plasticity of stem cells by integrating physiological,
      transcriptional and epigenetic inputs.

PMID- 15987773
TI  - Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial
      cell maturation.
AB  - We have previously shown that a forkhead transcription factor Foxa1 interacts
      with androgen signaling and controls prostate differentiated response. Here, we
      show the mouse Foxa1 expression marks the entire embryonic urogenital sinus
      epithelium (UGE), contrasting with Shh and Foxa2, which are restricted to the
      basally located cells during prostate budding. The Foxa1-deficient mouse prostate
      shows a severely altered ductal pattern that resembles primitive epithelial cords
      surrounded by thick stromal layers. Characterization of these mutant cells
      indicates a population of basal-like cells similar to those found in the
      embryonic UGE, whereas no differentiated or mature luminal epithelial cells are
      found in Foxa1-deficient epithelium. These phenotypic changes are accompanied
      with molecular aberrations, including focal epithelial activation of Shh and
      elevated Foxa2 and Notch1 in the null epithelium. Perturbed epithelial-stromal
      interactions induced by Foxa1-deficient epithelium is evident, as demonstrated by
      the expansion of surrounding smooth muscle and elevated levels of stromal factors
      (Bmp4, Fgf7, Fgf10 and Gli). The prostatic homeobox protein Nkx3.1, a known
      proliferation inhibitor, was downregulated in Foxa1-deficient epithelial cells,
      while several prostate-specific androgen-regulated markers, including a novel
      Foxa1 target, are absent in the null prostate. These data indicate that Foxa1
      plays a pivotal role in controlling prostate morphogenesis and cell
      differentiation.

PMID- 15987774
TI  - Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated
      directly by Forkhead and GATA transcription factors through a distal enhancer
      element.
AB  - The GATA family of zinc-finger transcription factors plays key roles in the
      specification and differentiation of multiple cell types during development.
      GATA4 is an early regulator of gene expression during the development of endoderm
      and mesoderm, and genetic studies in mice have demonstrated that GATA4 is
      required for embryonic development. Despite the importance of GATA4 in tissue
      specification and differentiation, the mechanisms by which Gata4 expression is
      activated and the transcription factor pathways upstream of GATA4 remain largely
      undefined. To identify transcriptional regulators of Gata4 in the mouse, we
      screened conserved noncoding sequences from the mouse Gata4 gene for enhancer
      activity in transgenic embryos. Here, we define the regulation of a distal
      enhancer element from Gata4 that is sufficient to direct expression throughout
      the lateral mesoderm, beginning at 7.5 days of mouse embryonic development. The
      activity of this enhancer is initially broad but eventually becomes restricted to
      the mesenchyme surrounding the liver. We demonstrate that the function of this
      enhancer in transgenic embryos is dependent upon highly conserved Forkhead and
      GATA transcription factor binding sites, which are bound by FOXF1 and GATA4,
      respectively. Furthermore, the activity of the Gata4 lateral mesoderm enhancer is
      attenuated by the BMP antagonist Noggin, and the enhancer is not activated in
      Bmp4-null embryos. Thus, these studies establish that Gata4 is a direct
      transcriptional target of Forkhead and GATA transcription factors in the lateral
      mesoderm, and demonstrate that Gata4 lateral mesoderm enhancer activation
      requires BMP4, supporting a model in which GATA4 serves as a downstream effector
      of BMP signaling in the lateral mesoderm.

PMID- 15987775
TI  - Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in
      the gastrulating embryo.
AB  - The maternal Toll signaling pathway sets up a nuclear gradient of the
      transcription factor Dorsal in the early Drosophila embryo. Dorsal activates
      twist and snail, and the Dorsal/Twist/Snail network activates and represses other
      zygotic genes to form the correct expression patterns along the dorsoventral
      axis. An essential function of this patterning is to promote ventral cell
      invagination during mesoderm formation, but how the downstream genes regulate
      ventral invagination is not known. We show here that wntD is a novel member of
      the Wnt family. The expression of wntD is activated by Dorsal and Twist, but the
      expression is much reduced in the ventral cells through repression by Snail.
      Overexpression of WntD in the early embryo inhibits ventral invagination,
      suggesting that the de-repressed WntD in snail mutant embryos may contribute to
      inhibiting ventral invagination. The overexpressed WntD inhibits invagination by
      antagonizing Dorsal nuclear localization, as well as twist and snail expression.
      Consistent with the early expression of WntD at the poles in wild-type embryos,
      loss of WntD leads to posterior expansion of nuclear Dorsal and snail expression,
      demonstrating that physiological levels of WntD can also attenuate Dorsal nuclear
      localization. We also show that the de-repressed WntD in snail mutant embryos
      contributes to the premature loss of snail expression, probably by inhibiting
      Dorsal. Thus, these results together demonstrate that WntD is regulated by the
      Dorsal/Twist/Snail network, and is an inhibitor of Dorsal nuclear localization
      and function.

PMID- 15987776
TI  - Pulmonary bioactivation of trichloroethylene to chloral hydrate: relative
      contributions of CYP2E1, CYP2F, and CYP2B1.
AB  - Pulmonary cytotoxicity induced by trichloroethylene (TCE) is associated with
      cytochrome P450-dependent bioactivation to reactive metabolites. In this
      investigation, studies were undertaken to test the hypothesis that TCE metabolism
      to chloral hydrate (CH) is mediated by cytochrome P450 enzymes, including CYP2E1,
      CYP2F, and CYP2B1. Recombinant rat CYP2E1 catalyzed TCE metabolism to CH with
      greater affinity than did the recombinant P450 enzymes, rat CYP2F4, mouse CYP2F2,
      rat CYP2B1, and human CYP2E1. The catalytic efficiencies of recombinant rat
      CYP2E1 (V(max)/K(m) = 0.79) for generating CH was greater than those of
      recombinant CYP2F4 (V(max)/K(m) = 0.27), recombinant mouse CYP2F2 (V(max)/K(m) =
      0.11), recombinant rat CYP2B1 (V(max)/K(m) = 0.07), or recombinant human CYP2E1
      (V(max)/K(m) = 0.02). Decreases in lung microsomal immunoreactive CYP2E1, CYP2F2,
      and CYP2B1 were manifested at varying time points after TCE treatment. The loss
      of immunoreactive CYP2F2 occurred before the loss of immunoreactive CYP2E1 and
      CYP2B1. These protein decreases coincided with marked reduction of lung
      microsomal p-nitrophenol hydroxylation and pentoxyresorufin O-dealkylation. Rates
      of CH formation in the microsomal incubations were time-dependent and were
      incremental from 5 to 45 min. The production of CH was also determined in human
      lung microsomal incubations. The rates were low and were detected in only three
      of eight subjects. These results showed that, although CYP2E1, CYP2F, and CYP2B1
      are all capable of generating CH, TCE metabolism is mediated with greater
      affinity by recombinant rat CYP2E1 than by recombinant CYP2F, CYP2B1, or human
      CYP2E1. Moreover, the rates of CH production were substantially higher in murine
      than in human lung.

PMID- 15987777
TI  - Oxidation of tamoxifen by human flavin-containing monooxygenase (FMO) 1 and FMO3
      to tamoxifen-N-oxide and its novel reduction back to tamoxifen by human
      cytochromes P450 and hemoglobin.
AB  - Tamoxifen (TAM), used as the endocrine therapy of choice for breast cancer,
      undergoes metabolism primarily forming N-desmethyltamoxifen, 4-hydroxytamoxifen,
      alpha-hydroxytamoxifen, and tamoxifen-N-oxide (TNO). Our earlier studies
      demonstrated that flavin-containing monooxygenases (FMOs) catalyze the formation
      of TNO. The current study demonstrates that human FMO1 and FMO3 catalyze TAM N
      oxidation to TNO and that cytochromes P450 (P450s), but not FMOs, reduce TNO to
      TAM. CYP1A1, CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4
      all reduced TNO, with CYP2A6, CYP1A1, and CYP3A4 producing the greatest
      reduction. A portion of TAM formed by CYP3A4-mediated reduction of TNO was
      further metabolized, but not TAM formed by the other P450s. TNO reduction by
      P450s is extremely rapid with considerable TAM formation detected at the earliest
      time point that products could be measured. TAM formation exhibited a lack of
      linearity with incubation time but increased linearly as a function of TNO and
      P450 concentration. TNO was converted into TAM by reduced hemoglobin (Hb) and
      NADPH-P450 oxidoreductase, suggesting involvement of the same heme-Fe(2+) complex
      in both Hb and P450s. The findings raise the question of whether the reductive
      activity may be nonenzymatic. Results of this in vitro study demonstrate the
      potential of TAM and TNO to be interconverted metabolically. FMO seems to be the
      major enzymatic oxidant, whereas several P450 enzymes and even reduced hemoglobin
      are capable of reducing TNO back to TAM. The possibility that these processes may
      comprise a metabolic cycle in vivo is discussed in this article.

PMID- 15987778
TI  - Phosphorylation-regulated endoplasmic reticulum retention signal in the renal
      outer-medullary K+ channel (ROMK).
AB  - The renal outer-medullary K+ channel (ROMK; Kir1.1) mediates K+ secretion in the
      renal mammalian nephron that is critical to both sodium and potassium
      homeostasis. The posttranscriptional expression of ROMK in the plasma membrane of
      cells is regulated by delivery of protein from endoplasmic reticulum (ER) to the
      cell surface and by retrieval by dynamin-dependent endocytic mechanisms in
      clathrin-coated pits. The S44 in the NH(2) terminus of ROMK1 can be
      phosphorylated by PKA and serum- and glucocorticoid-inducible kinase-1, and this
      process increases surface expression of functional channels. We present evidence
      that phosphorylation of S44 modulates channel expression by increasing its cell
      surface delivery consequent to suppression of a COOH-terminal ER retention
      signal. This phosphorylation switch of the ER retention signal could provide a
      pool of mature and properly folded channels for rapid delivery to the plasma
      membrane. The x-ray crystal structures of inward rectifier K+ channels have shown
      a close apposition of the NH(2) terminus with the distal COOH terminus of the
      adjacent subunit in the channel homotetramer, which is important to channel
      gating. Thus, NH(2)-terminal phosphorylation modifying a COOH-terminal ER
      retention signal in ROMK1 could serve as a checkpoint for proper subunit folding
      critical to channel gating.

PMID- 15987779
TI  - Evolution of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase-encoding genes
      in the yeast Saccharomyces cerevisiae.
AB  - The shikimate pathway resulting in three aromatic amino acids is initiated in
      different organisms by two and three 3-deoxy-d-arabino-heptulosonate-7-phosphate
      synthases, respectively. Aro3p and Aro4p are the yeast enzymes feedback-inhibited
      by phenylalanine and tyrosine, respectively. A yeast strain deficient in the
      general control transcriptional regulatory system of amino acid biosynthesis is
      unable to live in the presence of high amounts of phenylalanine and tyrosine.
      Here, we show that this yeast strain can be rescued by the expression of aroH
      from Escherichia coli encoding the tryptophan-regulated AroH as third isoenzyme.
      Yeast carrying Ec AroH as the only enzyme for the initial step of the shikimate
      pathway can grow in the absence of tryptophan. Without aromatic amino acids, this
      yeast strain survives only when the yeast ARO3 promoter instead of the ARO4
      promoter drives E. coli aroH. The detailed analysis of Aro3p and Aro4p revealed a
      triple feedback control by tyrosine/phenylalanine and tryptophan. Dissecting this
      control allowed engineering of Aro4p S195A as an enzyme, which is inhibited like
      AroH only by tryptophan. In addition, Aro4p variants were constructed that show
      an equally strong inhibition by tyrosine and tryptophan (Aro4p P165G Q302R) and
      in which the regulation by tyrosine and tryptophan was reversed (Aro4p P165G).
      Our data suggest that yeast possesses only two instead of three isogenes encoding
      3-deoxy-D-arabino-heptulosonate-7-phosphate synthases because both isoenzymes can
      be fine tuned by tryptophan as additional effector and because transcriptional
      regulation by the general control system can be induced as backup when aromatic
      amino acids in the environment are imbalanced.

PMID- 15987780
TI  - Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)
      associated SOD1 mutants.
AB  - Amyotrophic lateral sclerosis is a neurodegenerative syndrome associated with 114
      mutations in the gene encoding the cytosolic homodimeric enzyme Cu/Zn superoxide
      dismutase (SOD). In this article, we report that amyotrophic lateral sclerosis
      associated SOD mutations with distinctly different disease progression can be
      rationalized in terms of their folding patterns. The mutations are found to
      perturb the protein in multiple ways; they destabilize the precursor monomers
      (class 1), weaken the dimer interface (class 2), or both at the same time (class
      1 + 2). A shared feature of the mutational perturbations is a shift of the
      folding equilibrium toward poorly structured SOD monomers. We observed a link,
      coupled to the altered folding patterns, between protein stability, net charge,
      and survival time for the patients carrying the mutations.

PMID- 15987781
TI  - Variation in commercial rodent diets induces disparate molecular and
      physiological changes in the mouse uterus.
AB  - Although ovarian estrogen, estradiol-17beta, is a key modulator of normal
      reproductive functions, natural and synthetic compounds with estrogen-like
      activities can further influence reproductive functions. Plant-derived
      phytoestrogens specifically have received much attention because of associated
      health benefits. However, a comprehensive understanding of the beneficial and/or
      detrimental impacts of phytoestrogen consumption through commercial rodent diets
      on uterine biology and early pregnancy at the molecular level remains largely
      unexplored. Using multiple approaches, we demonstrate here that exposure of adult
      female mice to a commercial rodent diet with higher phytoestrogen levels
      facilitates uterine growth in the presence or absence of ovarian estrogen, alters
      uterine expression of estrogen-responsive genes, and advances the timing of
      implantation compared with a diet with lower phytoestrogen levels. The finding
      that variability in phytoestrogen content in commercial rodent diets, both within
      and between brands, influences experimental results stresses the importance of
      this investigation and raises caution for investigators using rodents as animal
      models.

PMID- 15987783
TI  - Enzyme replacement therapy results in substantial improvements in early clinical
      phenotype in a mouse model of globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD) or Krabbe disease is a devastating,
      degenerative neurological disorder caused by mutations in the
      galactosylceramidase (GALC) gene that severely affect enzyme activity. Currently,
      treatment options for this disorder are very limited. Enzyme replacement therapy
      (ERT) has been shown to be effective in lysosomal storage disorders with
      predominantly peripheral manifestations such as type I Gaucher's and Fabry's
      disease. Little however is known about the possible benefit of ERT in GLD, which
      has a substantial central nervous system component. In this study, we examined
      the effect of peripheral GALC injections in the twitcher mouse model of the
      disease. Although we were unable to block the precipitous decline that normally
      occurs just before death, we did observe significant early improvements in motor
      performance, a substantial attenuation in the initial failure to thrive, and an
      increase in life span. Immunohistochemical and activity analyses demonstrated
      GALC uptake in multiple tissues, including the brain. This was associated with a
      decrease in the abnormal accumulation of the GALC substrate psychosine, which is
      thought to play a pivotal role in disease pathology. These results indicate that
      peripheral ERT is likely to be beneficial in GLD.

PMID- 15987784
TI  - Evaluation based on systematic review of epidemiological evidence among Japanese
      populations: tobacco smoking and total cancer risk.
AB  - BACKGROUND: We evaluated the association between tobacco smoking and total cancer
      risk among Japanese populations based on a systematic review of epidemiological
      evidence. METHODS: Original data were obtained from searches of MEDLINE using
      PubMed, complemented with manual searches. Evaluation of associations was based
      on the strength of evidence and the magnitude of association, together with
      biological plausibility as previously evaluated by the International Agency for
      Research on Cancer. Meta-analysis of associations was also conducted to obtain
      summary estimates of association. RESULTS: A total of eight cohort studies were
      identified. In men, all studies consistently showed a moderately increased risk
      of total cancer in current smokers compared with never-smokers. In women, an
      increase in risk was seen but was weaker than in men. The summary relative risk
      was estimated as 1.53 (95% confidence interval 1.41-1.65). CONCLUSION: We
      conclude that there is convincing evidence that current tobacco smoking
      moderately increases the risk ( approximately 1.5 times) of total cancer in the
      Japanese population compared with never-smoking Japanese.

PMID- 15987782
TI  - Control of T helper 2 cell function and allergic airway inflammation by PKCzeta.
AB  - Asthma is a disease of chronic airway inflammation in which T helper (Th) 2 cells
      play a critical role. The molecular mechanisms controlling Th2 differentiation
      and function are of paramount importance in biology and immunology. PKCzeta has
      been implicated in the regulation of apoptosis and NF-kappaB, as well as in the
      control of T-dependent responses, although no defects were detected in naive T
      cells from PKCzeta-/- mice. Here, we report that PKCzeta is critical for IL-4
      signaling and Th2 differentiation. Thus, PKCzeta levels are increased during Th2
      differentiation, but not Th1 differentiation, of CD4+ T cells, and the loss of
      PKCzeta impairs the secretion of Th2 cytokines in vitro and in vivo, as well as
      the nuclear translocation and tyrosine phosphorylation of Stat6 and Jak1
      activation, essential downstream targets of IL-4 signaling. Moreover, PKCzeta-/-
      mice display dramatic inhibition of ovalbumin-induced allergic airway disease,
      strongly suggesting that PKCzeta can be a therapeutic target in asthma.

PMID- 15987785
TI  - Enhanced microarray performance using low complexity representations of the
      transcriptome.
AB  - Low abundance mRNAs are more difficult to examine using microarrays than high
      abundance mRNAs due to the effect of concentration on hybridization kinetics and
      signal-to-noise ratios. This report describes the use of low complexity
      representations (LCRs) of mRNA as the targets for cDNA microarrays. Individual
      sequences in LCRs are more highly represented than in the mRNA populations from
      which they are derived, leading to favorable hybridization kinetics. LCR targets
      permit the measurement of abundance changes that are difficult to measure using
      oligo(dT) priming for target synthesis. An oligo(dT)-primed target and three LCRs
      detect twice as many differentially regulated genes as could be detected by the
      oligo(dT)-primed target alone, in an experiment in which serum-starved
      fibroblasts responded to the reintroduction of serum. Thus, this target
      preparation strategy considerably increases the sensitivity of cDNA microarrays.

PMID- 15987786
TI  - Immobilized stem-loop structured probes as conformational switches for enzymatic
      detection of microbial 16S rRNA.
AB  - We have designed and evaluated novel DNA stem-loop structured probes for
      enzymatic detection of nucleic acid targets. These probes constitute a novel
      class of conformational switches for enzymatic activity, which in the absence of
      a target sterically shield an affinity label and upon hybridization of the target
      to the recognition sequence that forms the loop of the probe restore
      accessibility of the label for the binding of a reporter enzyme. Analysis of
      probe characteristics revealed stem stability as the most important parameter
      governing detection functionality, while other factors such as the length of
      linker molecules attaching the label to the stem-loop structure and the nature of
      the solid support proved to be less critical. Apparently, the bulky nature of the
      reporter enzyme facilitates shielding of the label in the absence of the target,
      thereby conferring considerable structural tolerance to the conformational switch
      system. The stem-loop structured probes allow sensitive detection of unlabeled
      nucleic acid targets. Employing a microtiter assay format, 4 ng of bacterial 16S
      ribosomal RNA corresponding to 8 fmol could be detected, which can be compared
      favorably with current immobilized molecular beacon concepts based on
      fluorescence detection.

PMID- 15987787
TI  - Conditional knockdown of Fgfr2 in mice using Cre-LoxP induced RNA interference.
AB  - RNA interference (RNAi)-mediated gene knockdown is a potent approach for studying
      gene function. We have previously reported a plasmid-based, tamoxifen-inducible
      gene knockdown system in cultured cells using a combined RNAi and Cre-LoxP
      system. Here, we validate this system in mouse and show that it can be used to
      suppress the expression of an endogenous gene (Fgfr2) with high efficiency. We
      show that transgenic mice carrying the U6-ploxPneo-Fgfr2 RNAi construct are
      normal, displaying Fgfr2 transcripts equivalent to those of wild-type controls,
      indicating that the U6 promoter is inactive in vivo due to the presence of the
      neo in the promoter. After excision of the neo by crossing with transgenic mice
      that express Cre in the mouse germline, the U6 promoter is activated, leading to
      over 95% reduction of Fgfr2 transcripts, and consequently, embryonic lethality.
      On the other hand, activation of the U6 promoter using transgenic mice that
      express Cre in the progress zone of the limb results in live mice with
      malformation of digits of both the forelimbs and hindlimbs. This method provides
      a fast, yet efficient way to decipher gene functions in vivo in a tissue-specific
      manner.

PMID- 15987788
TI  - EID3 is a novel EID family member and an inhibitor of CBP-dependent co
      activation.
AB  - EID1 (E1A-like inhibitor of differentiation 1) functions as an inhibitor of
      nuclear receptor-dependent gene transcription by directly binding to co
      regulators. Alternative targets include the co-repressor small heterodimer
      partner (SHP, NR0B2) and the co-activators CBP/p300, indicating that EID1
      utilizes different inhibitory strategies. Recently, EID2 was characterized as an
      inhibitor of muscle differentiation and as an antagonist of both CBP/p300 and
      HDACs. Here, we describe a third family member designated EID3 that is highly
      expressed in testis and shows homology to a region of EID1 implicated in binding
      to CBP/p300. We demonstrate that EID3 acts as a potent inhibitor of nuclear
      receptor transcriptional activity by a mechanism that is independent of direct
      interactions with nuclear receptors, including SHP. Furthermore, EID3 directly
      binds to and blocks the SRC-1 interacting domain of CBP, which has been
      implicated to act as the interaction surface for nuclear receptor co-activators.
      Consistent with this idea, EID3 prevents recruitment of CBP to a natural nuclear
      receptor-regulated promoter. Our study suggests that EID-family members EID3 and
      EID1 act as inhibitors of CBP/p300-dependent transcription in a tissue-specific
      manner.

PMID- 15987789
TI  - Human microRNA prediction through a probabilistic co-learning model of sequence
      and structure.
AB  - MicroRNAs (miRNAs) are small regulatory RNAs of approximately 22 nt. Although
      hundreds of miRNAs have been identified through experimental complementary DNA
      cloning methods and computational efforts, previous approaches could detect only
      abundantly expressed miRNAs or close homologs of previously identified miRNAs.
      Here, we introduce a probabilistic co-learning model for miRNA gene finding,
      ProMiR, which simultaneously considers the structure and sequence of miRNA
      precursors (pre-miRNAs). On 5-fold cross-validation with 136 referenced human
      datasets, the efficiency of the classification shows 73% sensitivity and 96%
      specificity. When applied to genome screening for novel miRNAs on human
      chromosomes 16, 17, 18 and 19, ProMiR effectively searches distantly homologous
      patterns over diverse pre-miRNAs, detecting at least 23 novel miRNA gene
      candidates. Importantly, the miRNA gene candidates do not demonstrate clear
      sequence similarity to the known miRNA genes. By quantitative PCR followed by RNA
      interference against Drosha, we experimentally confirmed that 9 of the 23
      representative candidate genes express transcripts that are processed by the
      miRNA biogenesis enzyme Drosha in HeLa cells, indicating that ProMiR may
      successfully predict miRNA genes with at least 40% accuracy. Our study suggests
      that the miRNA gene family may be more abundant than previously anticipated, and
      confer highly extensive regulatory networks on eukaryotic cells.

PMID- 15987790
TI  - Distinct regions of RPB11 are required for heterodimerization with RPB3 in human
      and yeast RNA polymerase II.
AB  - In Saccharomyces cerevisiae, RNA polymerase II assembly is probably initiated by
      the formation of the RPB3-RPB11 heterodimer. RPB3 is encoded by a single copy
      gene in the yeast, mouse and human genomes. The RPB11 gene is also unique in
      yeast and mouse, but in humans a gene family has been identified that potentially
      encodes several RPB11 proteins differing mainly in their C-terminal regions. We
      compared the abilities of both yeast and human proteins to heterodimerize. We
      show that the yeast RPB3/RPB11 heterodimer critically depends on the presence of
      the C-terminal region of RPB11. In contrast, the human heterodimer tolerates
      significant changes in RPB11 C-terminus, allowing two human RPB11 variants to
      heterodimerize with the same efficiency with RPB3. In keeping with this
      observation, the interactions between the conserved N-terminal 'alpha-motifs' is
      much more important for heterodimerization of the human subunits than for those
      in yeast. These data indicate that the heterodimerization interfaces have been
      modified during the course of evolution to allow a recent diversification of the
      human RPB11 subunits that remains compatible with heterodimerization with RPB3.

PMID- 15987791
TI  - Protein tyrosine phosphatase kappa and SHP-1 are involved in the regulation of
      cell-cell contacts at adherens junctions in the exocrine pancreas.
AB  - BACKGROUND: We have previously shown that cell contacts between pancreatic acinar
      cells dissociate early in pancreatitis and that this is a prerequisite for the
      development of pancreatic oedema. Here we studied the underlying mechanism.
      METHODS: Employing experimental caerulein induced pancreatitis in vivo and
      isolated pancreatic acini ex vivo, in conjunction with protein chemistry,
      morphology, and electron microscopy, we determined whether cell contact
      regulation in the pancreas requires or involves: (1) changes in cadherin-catenin
      protein expression, (2) tyrosine phosphorylation of adhesion proteins, or (3)
      alterations in the actin cytoskeleton. RESULTS: During initial cell-cell contact
      dissociation at adherens junctions, expression of adhesion proteins remained
      stable. At time points of dissociated adherens junctions, the cadherin-catenin
      complex was found to be tyrosine phosphorylated and internalised. The receptor
      type protein tyrosine phosphatase (PTP)kappa was constitutively associated with
      the cadherin-catenin complex at intact cell contacts whereas following the
      dissociation of adherens junctions, the internalised components of the cadherin
      catenin complex were tyrosine phosphorylated and associated with the cytosolic
      PTP SHP-1. In isolated acini, inhibition of endogenous protein tyrosine
      phosphatases alone was sufficient to induce dissociation of adherens junctions
      analogous to that found with supramaximal caerulein stimulation. Dissociation of
      actin microfilaments had no effect on adherens junction integrity. CONCLUSIONS:
      These data identify tyrosine phosphorylation as the key regulator for cell
      contacts at adherens junctions and suggest a definitive role for the protein
      tyrosine phosphatases PTPkappa and SHP-1 in the regulation, maintenance, and
      restitution of cell adhesions in a complex epithelial organ such as the pancreas.

PMID- 15987792
TI  - Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal
      mechanosensory function.
AB  - AIMS: Members of the acid sensing ion channel (ASIC) family are strong candidates
      as mechanical transducers in sensory function. The authors have shown that ASIC1a
      has no role in skin but a clear influence in gastrointestinal
      mechanotransduction. Here they investigate further ASIC1a in gut
      mechanoreceptors, and compare its influence with ASIC2 and ASIC3. METHODS AND
      RESULTS: Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and
      dorsal root ganglia (DRG), and was lost in mice lacking the respective genes.
      Recordings of different classes of splanchnic colonic afferents and vagal gastro
      oesophageal afferents revealed that disruption of ASIC1a increased the mechanical
      sensitivity of all afferents in both locations. Disruption of ASIC2 had varied
      effects: increased mechanosensitivity in gastro-oesophageal mucosal endings,
      decreases in gastro-oesophageal tension receptors, increases in colonic serosal
      endings, and no change in colonic mesenteric endings. In ASIC3-/- mice, all
      afferent classes had markedly reduced mechanosensitivity except gastro
      oesophageal mucosal receptors. Observations of gastric emptying and faecal output
      confirmed that increases in mechanosensitivity translate to changes in digestive
      function in conscious animals. CONCLUSIONS: These data show that ASIC3 makes a
      critical positive contribution to mechanosensitivity in three out of four classes
      of visceral afferents. The presence of ASIC1a appears to provide an inhibitory
      contribution to the ion channel complex, whereas the role of ASIC2 differs widely
      across subclasses of afferents. These findings contrast sharply with the effects
      of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with
      pharmacological agents may have different and more pronounced effects on
      mechanosensitivity in the viscera.

PMID- 15987793
TI  - Complete cystic fibrosis transmembrane conductance regulator gene sequencing in
      patients with idiopathic chronic pancreatitis and controls.
AB  - BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene-many of which cause cystic fibrosis-have also been reported in
      patients with chronic pancreatitis. The authors examine whether mild or severe
      CFTR mutations, homozygous or compound heterozygous CFTR mutations, or even
      simple cystic fibrosis carrier status alone increases the risk of developing
      pancreatitis. METHODS: After exclusion of patients with trypsinogen (PRSS1)
      mutations, cystic fibrosis, or pulmonary disease, and with known risk factors for
      pancreatitis 67 patients with idiopathic chronic pancreatitis (ICP) from
      northwest Germany and 60 geographically and ethnically matched controls were
      recruited. The entire coding region of the CFTR gene was sequenced in all
      patients and controls. ICP patients were also analysed for serine protease
      inhibitor Kazal type 1 (SPINK1) gene mutations. RESULTS: Abnormal CFTR alleles
      were found to be twice as frequent in ICP patients as in controls (25/134 v
      11/120; p<0.05). Three of four severe CFTR mutations detected in patients were
      compound heterozygous with another abnormal CFTR allele, whereas among controls
      three severe CFTR mutations were found in heterozygous cystic fibrosis carriers.
      In ICP patients 19 uncommon/mild mutations, including combinations of the 5T
      allele with 12TG repeats, were identified compared with only five in controls (p
      = 0.012). Heterozygous SPINK1 mutations were detected in eight ICP patients (15%
      v 1% in controls) but only one also carried an additional mild CFTR mutation.
      CONCLUSIONS: These data show that not only compound heterozygosity, but also
      cystic fibrosis carrier status for different types of CFTR mutations, including
      uncommon/mild mutations, significantly increase the risk of developing
      pancreatitis. Although 45% of the study's ICP patients carried predisposing
      genetic risk factors (for example, mutations in CFTR or SPINK1), the authors
      found no evidence that the risk conveyed by CFTR mutations depends on co
      inherited SPINK1 mutations.

PMID- 15987794
TI  - Acute induction of human IL-8 production by intestinal epithelium triggers
      neutrophil infiltration without mucosal injury.
AB  - AIM: Neutrophil migration in the intestine depends on chemotaxis of neutrophils
      to CXC chemokines produced by epithelial cells. The goal of this project was to
      determine if acute induction of a CXC chemokine gradient originating from
      intestinal epithelial cells is sufficient to induce neutrophil influx into intact
      intestinal tissue. METHODS AND RESULTS: The authors developed a double transgenic
      mouse model with doxycycline induced human IL-8 expression restricted to
      intestinal epithelial cells. Doxycycline treatment of double transgenic mice for
      three days resulted in a 50-fold increase in the caecal IL-8 concentration and
      influx of neutrophils into the lamina propria. Although neutrophils entered the
      paracellular space between epithelial cells, complete transepithelial migration
      was not observed. Doxycycline treatment also increased the water content of the
      caecal and colonic stool, indicating dysfunctional water transport. However, the
      transmural electrical resistance was not decreased. Neutrophils recruited to the
      intestinal epithelium did not show evidence of degranulation and the epithelium
      remained intact as judged by histology. CONCLUSIONS: This conditional transgenic
      model of chemokine expression provides evidence that acute induction of IL-8 in
      the intestinal epithelium is sufficient to trigger neutrophil recruitment to the
      lamina propria, but additional activation signals are needed for full activation
      and degranulation of neutrophils, mucosal injury, and complete transepithelial
      migration.

PMID- 15987795
TI  - Influence of intestinal bacteria on induction of regulatory T cells: lessons from
      a transfer model of colitis.
AB  - BACKGROUND: The resident flora plays a critical role in initiation and
      perpetuation of intestinal inflammation, as demonstrated in experimental models
      of colitis where animals fail to develop disease under germ free conditions.
      However, the importance of exposure to commensal bacteria before the onset of
      colitis is unclear. Our aim was to investigate the influence of previous exposure
      of donor animals to bacterial antigens on colitis development using a transfer
      model. METHODS: Clinical course and histology were evaluated after transfer of
      CD4(+)CD62L(+) lymphocytes from germ free and conventionally housed donor mice
      into SCID recipients. Cotransfer of CD4(+)CD62L(+) cells with CD4(+)CD62L(-
      )lymphocytes from both groups of mice was initiated. Lymphocytes were analysed by
      FACS, polarisation potential of cells determined, and cytokines measured within
      the supernatant by enzyme linked immunosorbent assay. RESULTS: Animals that
      received cells from germ free donors developed an earlier onset of colitis
      compared with mice reconstituted with lymphocytes from conventionally housed
      animals. Additionally, CD4(+)CD62L(- )cells from germ free mice were not able to
      abrogate colitis induced by cotransfer with CD4(+)CD62L(+) lymphocytes whereas
      CD4(+)CD62L(- )T cells from normal mice ameliorated disease. The higher
      percentage of CD4(+)GITR(+) expressing lymphocytes and the production of
      interleukin 10 after priming by dendritic cells suggests the presence of T(reg)
      cells within the CD4(+)CD62L(+) lymphocyte subset derived from conventional
      housed mice and assumes a lack of T(reg) cells within germ free mice. CONCLUSION:
      The results indicate that bacterial antigens are crucial for the generation
      and/or expansion of T(reg) cells in a healthy individual. Therefore, bacterial
      colonisation is of great importance in maintaining the immunological balance.

PMID- 15987796
TI  - Thin and strong! The bioengineering dilemma in the structural and functional
      design of the blood-gas barrier.
AB  - In gas exchangers, the tissue barrier, the partition that separates the
      respiratory media (water/air and hemolymph/blood), is exceptional for its
      remarkable thinness, striking strength, and vast surface area. These properties
      formed to meet conflicting roles: thinness was essential for efficient flux of
      oxygen by passive diffusion, and strength was crucial for maintaining structural
      integrity. What we have designated as "three-ply" or "laminated tripartite"
      architecture of the barrier appeared very early in the evolution of the
      vertebrate gas exchanger. The design is conspicuous in the water-blood barrier of
      the fish gills through the lungs of air-breathing vertebrates, where the plan
      first appeared in lungfishes (Dipnoi) some 400 million years ago. The similarity
      of the structural design of the barrier in respiratory organs of animals that
      remarkably differ phylogenetically, behaviorally, and ecologically shows that the
      construction has been highly conserved both vertically and horizontally, i.e.,
      along and across the evolutionary continuum. It is conceivable that the blueprint
      may have been the only practical construction that could simultaneously grant
      satisfactory strength and promote gas exchange. In view of the very narrow
      allometric range of the thickness of the blood-gas barrier in the lungs of
      different-sized vertebrate groups, the measurement has seemingly been optimized.
      There is convincing, though indirect, evidence that the extracellular matrix and
      particularly the type IV collagen in the lamina densa of the basement membrane is
      the main stress-bearing component of the blood-gas barrier. Under extreme
      conditions of operation and in some disease states, the barrier fails with
      serious consequences. The lamina densa which in many parts of the blood-gas
      barrier is <50 nm thin is a lifeline in the true sense of the word.

PMID- 15987797
TI  - The retinal pigment epithelium in visual function.
AB  - Located between vessels of the choriocapillaris and light-sensitive outer
      segments of the photoreceptors, the retinal pigment epithelium (RPE) closely
      interacts with photoreceptors in the maintenance of visual function. Increasing
      knowledge of the multiple functions performed by the RPE improved the
      understanding of many diseases leading to blindness. This review summarizes the
      current knowledge of RPE functions and describes how failure of these functions
      causes loss of visual function. Mutations in genes that are expressed in the RPE
      can lead to photoreceptor degeneration. On the other hand, mutations in genes
      expressed in photoreceptors can lead to degenerations of the RPE. Thus both
      tissues can be regarded as a functional unit where both interacting partners
      depend on each other.

PMID- 15987798
TI  - Ion channel development, spontaneous activity, and activity-dependent development
      in nerve and muscle cells.
AB  - At specific stages of development, nerve and muscle cells generate spontaneous
      electrical activity that is required for normal maturation of intrinsic
      excitability and synaptic connectivity. The patterns of this spontaneous activity
      are not simply immature versions of the mature activity, but rather are highly
      specialized to initiate and control many aspects of neuronal development. The
      configuration of voltage- and ligand-gated ion channels that are expressed early
      in development regulate the timing and waveform of this activity. They also
      regulate Ca2+ influx during spontaneous activity, which is the first step in
      triggering activity-dependent developmental programs. For these reasons, the
      properties of voltage- and ligand-gated ion channels expressed by developing
      neurons and muscle cells often differ markedly from those of adult cells. When
      viewed from this perspective, the reasons for complex patterns of ion channel
      emergence and regression during development become much clearer.

PMID- 15987799
TI  - Controlling cell behavior electrically: current views and future potential.
AB  - Direct-current (DC) electric fields are present in all developing and
      regenerating animal tissues, yet their existence and potential impact on tissue
      repair and development are largely ignored. This is primarily due to ignorance of
      the phenomenon by most researchers, some technically poor early studies of the
      effects of applied fields on cells, and widespread misunderstanding of the
      fundamental concepts that underlie bioelectricity. This review aims to resolve
      these issues by describing: 1) the historical context of bioelectricity, 2) the
      fundamental principles of physics and physiology responsible for DC electric
      fields within cells and tissues, 3) the cellular mechanisms for the effects of
      small electric fields on cell behavior, and 4) the clinical potential for
      electric field treatment of damaged tissues such as epithelia and the nervous
      system.

PMID- 15987800
TI  - Expression and function of laminins in the embryonic and mature vasculature.
AB  - Endothelial cells of the blood and lymphatic vasculature are polarized cells with
      luminal surfaces specialized to interact with inflammatory cells upon the
      appropriate stimulation; they contain specialized transcellular transport
      systems, and their basal surfaces are attached to an extracellular basement
      membrane. In adult tissues the basement membrane forms a continuous sleeve around
      the endothelial tubes, and the interaction of endothelial cells with basement
      membrane components plays an important role in the maintenance of vessel wall
      integrity. During development, the basement membrane of endothelium provides
      distinct spatial and molecular information that influences endothelial cell
      proliferation, migration, and differentiation/maturation. Microvascular
      endothelium matures into phenotypically distinct types: continuous, fenestrated,
      and discontinuous, which also differ in their permeability properties.
      Development of these morphological and physiological differences is thought to be
      controlled by both soluble factors in the organ or tissue environment and by cell
      cell and cell-matrix interactions. Basement membranes of endothelium, like those
      of other tissues, are composed of laminins, type IV collagens, heparan sulfate
      proteoglycans, and nidogens. However, isoforms of all four classes of molecules
      exist, which combine to form structurally and functionally distinct basement
      membranes. The endothelial cell basement membranes have been shown to be unique
      with respect to their laminin isoform composition. Laminins are a family of
      glycoprotein heterotrimers composed of an alpha, beta, and gamma chain. To date,
      5alpha, 4beta, and 3gamma laminin chains have been identified that can combine to
      form 15 different isoforms. The laminin alpha-chains are considered to be the
      functionally important portion of the heterotrimers, as they exhibit tissue
      specific distribution patterns and contain the major cell interaction sites.
      Vascular endothelium expresses only two laminin isoforms, and their expression
      varies depending on the developmental stage, vessel type, and the activation
      state of the endothelium. Laminin 8 (composed of laminin alpha4, beta1, and
      gamma1 chains) is expressed by all endothelial cells regardless of their stage of
      development, and its expression is strongly upregulated by cytokines and growth
      factors that play a role in inflammatory events. Laminin 10 (composed of laminin
      alpha5, beta1, and gamma1 chains) is detectable primarily in endothelial cell
      basement membranes of capillaries and venules commencing 3-4 wk after birth. In
      contrast to laminin 8, endothelial cell expression of laminin 10 is upregulated
      only by strong proinflammatory signals and, in addition, angiostatic agents such
      as progesterone. Other extracellular matrix molecules, such as BM40 (also known
      as SPARC/osteonectin), thrombospondins 1 and 2, fibronectin, nidogens 1 and 2,
      and collagen types VIII, XV, and XVIII, are also differentially expressed by
      endothelium, varying with the endothelium type and/or pathophysiological state.
      The data argue for a dynamic endothelial cell extracellular matrix that presents
      different molecular information depending on the type of endothelium and/or
      physiological situation. This review outlines the unique structural and
      functional features of vascular basement membranes, with focus on the endothelium
      and the laminin family of glycoproteins.

PMID- 15987801
TI  - Invertebrate muscles: muscle specific genes and proteins.
AB  - This is the first of a projected series of canonic reviews covering all
      invertebrate muscle literature prior to 2005 and covers muscle genes and proteins
      except those involved in excitation-contraction coupling (e.g., the ryanodine
      receptor) and those forming ligand- and voltage-dependent channels. Two themes
      are of primary importance. The first is the evolutionary antiquity of muscle
      proteins. Actin, myosin, and tropomyosin (at least, the presence of other muscle
      proteins in these organisms has not been examined) exist in muscle-like cells in
      Radiata, and almost all muscle proteins are present across Bilateria, implying
      that the first Bilaterian had a complete, or near-complete, complement of present
      day muscle proteins. The second is the extraordinary diversity of protein
      isoforms and genetic mechanisms for producing them. This rich diversity suggests
      that studying invertebrate muscle proteins and genes can be usefully applied to
      resolve phylogenetic relationships and to understand protein assembly
      coevolution. Fully achieving these goals, however, will require examination of a
      much broader range of species than has been heretofore performed.

PMID- 15987802
TI  - Structure and function of CLCA proteins.
AB  - CLCA proteins were discovered in bovine trachea and named for a calcium-dependent
      chloride conductance found in trachea and in other secretory epithelial tissues.
      At least four closely located gene loci in the mouse and the human code for
      independent isoforms of CLCA proteins. Full-length CLCA proteins have an
      unprocessed mass ratio of approximately 100 kDa. Three of the four human loci
      code for the synthesis of membrane-associated proteins. CLCA proteins affect
      chloride conductance, epithelial secretion, cell-cell adhesion, apoptosis, cell
      cycle control, mucus production in asthma, and blood pressure. There is a
      structural and probable functional divergence between CLCA isoforms containing or
      not containing beta4-integrin binding domains. Cell cycle control and tumor
      metastasis are affected by isoforms with the binding domains. These isoforms are
      expressed prominently in smooth muscle, in some endothelial cells, in the central
      nervous system, and also in secretory epithelial cells. The isoform with
      disrupted beta4-integrin binding (hCLCA1, pCLCA1, mCLCA3) alters epithelial mucus
      secretion and ion transport processes. It is preferentially expressed in
      secretory epithelial tissues including trachea and small intestine. Chloride
      conductance is affected by the expression of several CLCA proteins. However, the
      dependence of the resulting electrical signature on the expression system rather
      than the CLCA protein suggests that these proteins are not independent Ca2+
      dependent chloride channels, but may contribute to the activity of chloride
      channels formed by, or in conjunction with, other proteins.

PMID- 15987803
TI  - Myocardial substrate metabolism in the normal and failing heart.
AB  - The alterations in myocardial energy substrate metabolism that occur in heart
      failure, and the causes and consequences of these abnormalities, are poorly
      understood. There is evidence to suggest that impaired substrate metabolism
      contributes to contractile dysfunction and to the progressive left ventricular
      remodeling that are characteristic of the heart failure state. The general
      concept that has recently emerged is that myocardial substrate selection is
      relatively normal during the early stages of heart failure; however, in the
      advanced stages there is a downregulation in fatty acid oxidation, increased
      glycolysis and glucose oxidation, reduced respiratory chain activity, and an
      impaired reserve for mitochondrial oxidative flux. This review discusses 1) the
      metabolic changes that occur in chronic heart failure, with emphasis on the
      mechanisms that regulate the changes in the expression of metabolic genes and the
      function of metabolic pathways; 2) the consequences of these metabolic changes on
      cardiac function; 3) the role of changes in myocardial substrate metabolism on
      ventricular remodeling and disease progression; and 4) the therapeutic potential
      of acute and long-term manipulation of cardiac substrate metabolism in heart
      failure.

PMID- 15987804
TI  - New ligase-derived RNA polymerase ribozymes.
AB  - The search is underway for a catalytic RNA molecule capable of self-replication.
      Finding such a ribozyme would lend crucial support to the RNA World hypothesis,
      which holds that very early life-forms relied on RNA for both replicating and
      storing genetic information. We previously reported an RNA polymerase isolated
      from a pool of variants of an existing RNA ligase ribozyme. Here we report eight
      additional ligase-derived polymerase ribozymes isolated from this pool. Because
      each of them is a new potential starting point for further in vitro evolution and
      engineering, together they substantially enrich the set of candidates from which
      an RNA replicase ribozyme might eventually emerge.

PMID- 15987805
TI  - Genome-wide analyses of two families of snoRNA genes from Drosophila
      melanogaster, demonstrating the extensive utilization of introns for coding of
      snoRNAs.
AB  - Small nucleolar RNAs (snoRNAs) are an abundant group of noncoding RNAs mainly
      involved in the post-transcriptional modifications of rRNAs in eukaryotes. In
      this study, a large-scale genome-wide analysis of the two major families of
      snoRNA genes in the fruit fly Drosophila melanogaster has been performed using
      experimental and computational RNomics methods. Two hundred and twelve gene
      variants, encoding 56 box H/ACA and 63 box C/D snoRNAs, were identified, of which
      57 novel snoRNAs have been reported for the first time. These snoRNAs were
      predicted to guide a total of 147 methylations and pseudouridylations on rRNAs
      and snRNAs, showing a more comprehensive pattern of rRNA modification in the
      fruit fly. With the exception of nine, all the snoRNAs identified to date in D.
      melanogaster are intron encoded. Remarkably, the genomic organization of the
      snoRNAs is characteristic of 8 dUhg genes and 17 intronic gene clusters,
      demonstrating that distinct organizations dominate the expression of the two
      families of snoRNAs in the fruit fly. Of the 267 introns in the host genes, more
      than half have been identified as host introns for coding of snoRNAs. In contrast
      to mammals, the variation in size of the host introns is mainly due to
      differences in the number of snoRNAs they contain. These results demonstrate the
      extensive utilization of introns for coding of snoRNAs in the host genes and shed
      light on further research of other noncoding RNA genes in the large introns of
      the Drosophila genome.

PMID- 15987806
TI  - Induced fit of RNA on binding the L7Ae protein to the kink-turn motif.
AB  - The kink-turn is a widespread motif in RNA consisting of a three-nucleotide bulge
      flanked on one side by consecutive A3G mismatches. Important examples are found
      in the ribosome, U4 RNA, and in snoRNAs involved in RNA modification. The motif
      is a common protein binding site, and the RNA has been found to adopt a tightly
      kinked conformation in crystal structures. However, in free solution there is a
      dynamic exchange between kinked and extended conformations, with the equilibrium
      driven toward the kinked form by the addition of metal ions. Here we used
      fluorescence resonance energy transfer (FRET) to show that the L7Ae protein of
      Archaeoglobus fulgidus binds to RNA containing a kink-turn with nanomolar
      affinity, and induces folding into the tightly kinked conformation even in the
      absence of metal ions. Thus this RNA may act as a relatively flexible hinge
      during RNA folding, until fixed into its ultimate kinked structure by the binding
      of L7 or related protein.

PMID- 15987807
TI  - An end-healing enzyme from Clostridium thermocellum with 5' kinase, 2',3'
      phosphatase, and adenylyltransferase activities.
AB  - We identify and characterize an end-healing enzyme, CthPnkp, from Clostridium
      thermocellum that catalyzes the phosphorylation of 5'-OH termini of DNA or RNA
      polynucleotides and the dephosphorylation of 2',3' cyclic phosphate, 2'
      phosphate, and 3'-phosphate ribonucleotides. CthPnkp also catalyzes an
      autoadenylylation reaction via a polynucleotide ligase-type mechanism. These
      characteristics are consistent with a role in end-healing during RNA or DNA
      repair. CthPnkp is a homodimer of an 870-amino-acid polypeptide composed of three
      catalytic domains: an N-terminal module that resembles the polynucleotide kinase
      domain of bacteriophage T4 Pnkp, a central metal-dependent phosphoesterase
      module, and a C-terminal module that resembles the nucleotidyl transferase domain
      of polynucleotide ligases. The distinctive feature of CthPnkp vis-a-vis known RNA
      repair enzymes is that its 3' end modification component belongs to the
      calcineurin-type phosphatase superfamily. It contains putative counterparts of
      the amino acids that form the dinuclear metal-binding site and the phosphate
      binding site of bacteriophage lambda phosphatase. As with lambda phosphatase, the
      2',3' cAMP phosphatase activity of CthPnkp is specifically dependent on nickel or
      manganese. We identify homologs of CthPnkp in other bacterial proteomes.

PMID- 15987808
TI  - Biochemical and genomic analysis of substrate recognition by the double-stranded
      RNA binding domain of yeast RNase III.
AB  - Members of the RNase III family of double-stranded RNA (dsRNA) endonucleases are
      important enzymes of RNA metabolism in eukaryotic cells. Rnt1p is the only known
      member of the RNase III family of endonucleases in Saccharomyces cerevisiae.
      Previous studies have shown that Rnt1p cleaves dsRNA capped by a conserved AGNN
      tetraloop motif, which is a major determinant for Rnt1p binding and cleavage. The
      solution structure of the dsRNA-binding domain (dsRBD) of Rnt1p bound to a
      cognate RNA substrate revealed the structural basis for binding of the conserved
      tetraloop motif by alpha-helix 1 of the dsRBD. In this study, we have analyzed
      extensively the effects of mutations of helix 1 residues that contact the RNA. We
      show, using microarray analysis, that mutations of these amino acids induce
      substrate-specific processing defects in vivo. Cleavage kinetics and binding
      studies show that these mutations affect RNA cleavage and binding in vitro to
      different extents and suggest a function for some specific amino acids of the
      dsRBD in the catalytic positioning of the enzyme. Moreover, we show that 2'
      hydroxyl groups of nucleotides of the tetraloop or adjacent base pairs predicted
      to interact with residues of alpha-helix 1 are important for Rnt1p cleavage in
      vitro. This study underscores the importance of a few amino acid contacts for
      positioning of a dsRBD onto its RNA target, and implicates the specific
      orientation of helix 1 on the RNA for proper positioning of the catalytic domain.

PMID- 15987809
TI  - Characterization of a highly variable eutherian microRNA gene.
AB  - Mouse microRNAs (miRNAs) miR-290-miR295 are encoded by a cluster of partially
      homologous pre-miRNA hairpins and are likely to be functionally important in
      embryonic stem (ES) cells and preimplantation embryos. We present evidence that a
      spliced, capped, and polyadenylated primary transcript spans this entire Early
      Embryonic microRNA Cluster (EEmiRC). Partial Drosha processing yields additional
      large nuclear RNA intermediates. A conserved promoter element containing a TATA
      box directs EEmiRC transcription. Sequence analysis shows that the EEmiRC
      transcription unit is remarkably variable and can only be identified
      bioinformatically in placental (eutherian) mammals. Consistent with eutherian
      specific function, EEmiRC is expressed in trophoblastic stem (TS) cells. When
      analyzing evolutionary and functional relationships, the organization of the
      entire miRNA loci should be considered in addition to the mature miRNA sequences.
      Application of this concept suggests that EEmiRC is a recently acquired rapidly
      evolving gene important for eutherian development.

PMID- 15987810
TI  - Crystal structure and functional analysis of DEAD-box protein Dhh1p.
AB  - The control of mRNA translation and degradation are critical for proper gene
      expression. A key regulator of both translation and degradation is Dhh1p, which
      is a DEAD-box protein, and functions both to repress translation and enhance
      decapping. We describe the crystal structure of the N- and C-terminal truncated
      Dhh1p (tDhh1p) determined at 2.1 A resolution. This reveals that, like other DEAD
      box proteins, tDhh1p contains two RecA-like domains, although with a unique
      arrangement. In contrast to eIF4A and mjDEAD, in which no motif interactions
      exist, in Dhh1p, motif V interacts with motif I and the Q-motif, thereby linking
      the two domains together. Electrostatic potential mapping combined with
      mutagenesis reveals that motifs I, V, and VI are involved in RNA binding. In
      addition, trypsin digestion of tDhh1p suggests that ATP binding enhances an RNA
      induced conformational change. Interestingly, some mutations located in the
      conserved motifs and at the interface between the two Dhh1 domains confer
      dominant negative phenotypes in vivo and disrupt the conformational switch in
      vitro. This suggests that this conformational change is required in Dhh1 function
      and identifies key residues involved in that transition.

PMID- 15987811
TI  - A potential link between transgene silencing and poly(A) tails.
AB  - Argonaute proteins function in gene silencing induced by double-stranded RNA
      (dsRNA) in various organisms. In Drosophila, the Argonaute proteins AGO1 and AGO2
      have been implicated in post-transcriptional gene-silencing (PTGS)/RNA
      interference (RNAi). In this study, we found that AGO1 and AGO2 depletion caused
      the accumulation of multicopied enhanced green fluorescence protein (EGFP)
      transgene transcripts in Drosophila S2 cells. Depletion of AGO1, the essential
      factor for miRNA biogenesis, led to an increased transcriptional rate of the
      transgenes. In contrast, depletion of AGO2, the essential factor for siRNA
      directed RNAi, resulted in EGFP mRNA stabilization with concomitant shortening of
      the EGFP mRNA poly(A) tail. Our findings suggest that AGO1 and AGO2 mediate
      multicopied transgene silencing by different mechanisms. Intriguingly, Dicer2
      depletion phenocopies AGO2 depletion, with an increase in EGFP protein levels and
      shortening of the EGFP mRNA poly(A) tail. The possibility that AGO2 and Dicer2
      involve, at least in part, poly(A) length maintenance of transgene mRNA suggests
      a potentially important link between transgene silencing and poly(A) tails.

PMID- 15987812
TI  - NMR spectroscopy of RNA duplexes containing pseudouridine in supercooled water.
AB  - We have performed NMR experiments in supercooled water in order to decrease the
      temperature-dependent exchange of protons in RNA duplexes. NMR spectra of aqueous
      samples of RNA in bundles of narrow capillaries that were acquired at
      temperatures as low as -18 degrees C reveal resonances of exchangeable protons
      not seen at higher temperatures. In particular, we detected the imino protons of
      terminal base pairs and the imino proton of a non-base-paired pseudouridine in a
      duplex representing the eukaryotic pre-mRNA branch site helix. Analysis of the
      temperature dependence of chemical shift changes (thermal coefficients) for imino
      protons corroborated hydrogen bonding patterns observed in the NMR-derived
      structural model of the branch site helix. The ability to observe non-base-paired
      imino protons of RNA is of significant value in structure determination of RNA
      motifs containing loop and bulge regions.

PMID- 15987813
TI  - The positional, structural, and sequence requirements of the Drosophila TLS RNA
      localization element.
AB  - The subcellular localization of mRNAs is a key step in the polarization of cells
      in organisms from yeast to man. Here, we use a transgenic fly/in situ
      hybridization assay system to define the positional, structural, and sequence
      requirements of the TLS, a stem loop RNA sequence element that mediates the
      subcellular localization of K10 and Orb transcripts in Drosophila oocytes. We
      find that the TLS is a highly robust and modular element. It mediates efficient
      RNA localization regardless of sequence context or position within the
      transcript. Site-specific mutagenesis experiments indicate that the size and
      shape of the stem and loop regions are critical determinants of TLS activity.
      Such experiments also identify specific base residues that are important for TLS
      activity. All such residues map to the stem portion of the structure.
      Significantly, mutations at these residues interfere with TLS activity only when
      they alter the stereochemistry of the stem's minor groove. For example, mutation
      of the A:U base pair at position 3 of the TLS stem to G:C severely reduces TLS
      activity, while mutation of the same base pair to U:A has no effect. Extensive
      searches for TLS-like elements in other Drosophila mRNAs using sequence and
      structural parameters defined by our experiments indicate that the TLS is unique
      to K10 and Orb mRNAs. This unexpected finding raises important questions as to
      how the many hundreds of other mRNAs that are known or thought to exhibit K10 and
      Orb-like localization are localized.

PMID- 15987814
TI  - The stem-loop binding protein stimulates histone translation at an early step in
      the initiation pathway.
AB  - Metazoan replication-dependent histone mRNAs do not have a poly(A) tail but end
      instead in a conserved stem-loop structure. Efficient translation of these mRNAs
      is dependent on the stem-loop binding protein (SLBP). Here we explore the
      mechanism by which SLBP stimulates translation in vertebrate cells, using the
      tethered function assay and analyzing protein-protein interactions. We show for
      the first time that translational stimulation by SLBP increases during oocyte
      maturation and that SLBP stimulates translation at the level of initiation. We
      demonstrate that SLBP can interact directly with subunit h of eIF3 and with
      Paip1; however, neither of these interactions is sufficient to mediate its
      effects on translation. We find that Xenopus SLBP1 functions primarily at an
      early stage in the cap-dependent initiation pathway, targeting small ribosomal
      subunit recruitment. Analysis of IRES-driven translation in Xenopus oocytes
      suggests that SLBP activity requires eIF4E. We propose a model in which a novel
      factor contacts eIF4E bound to the 5' cap and SLBP bound to the 3' end
      simultaneously, mediating formation of an alternative end-to-end complex.

PMID- 15987815
TI  - The Cm56 tRNA modification in archaea is catalyzed either by a specific 2'-O
      methylase, or a C/D sRNP.
AB  - We identified the first archaeal tRNA ribose 2'-O-methylase, aTrm56, belonging to
      the Cluster of Orthologous Groups (COG) 1303 that contains archaeal genes only.
      The corresponding protein exhibits a SPOUT S-adenosylmethionine (AdoMet)
      dependent methyltransferase domain found in bacterial and yeast G18 tRNA 2'-O
      methylases (SpoU, Trm3). We cloned the Pyrococcus abyssi PAB1040 gene belonging
      to this COG, expressed and purified the corresponding protein, and showed that in
      vitro, it specifically catalyzes the AdoMet-dependent 2'-O-ribose methylation of
      C at position 56 in tRNA transcripts. This tRNA methylation is present only in
      archaea, and the gene for this enzyme is present in all the archaeal genomes
      sequenced up to now, except in the crenarchaeon Pyrobaculum aerophilum. In this
      archaea, the C56 2'-O-methylation is provided by a C/D sRNP. Our work is the
      first demonstration that, within the same kingdom, two different mechanisms are
      used to modify the same nucleoside in tRNAs.

PMID- 15987816
TI  - A surprisingly large RNase P RNA in Candida glabrata.
AB  - We have found an extremely large ribonuclease P (RNase P) RNA (RPR1) in the human
      pathogen Candida glabrata and verified that this molecule is expressed and
      present in the active enzyme complex of this hemiascomycete yeast. A structural
      alignment of the C. glabrata sequence with 36 other hemiascomycete RNase P RNAs
      (abbreviated as P RNAs) allows us to characterize the types of insertions. In
      addition, 15 P RNA sequences were newly characterized by searching in the
      recently sequenced genomes Candida albicans, C. glabrata, Debaryomyces hansenii,
      Eremothecium gossypii, Kluyveromyces lactis, Kluyveromyces waltii, Naumovia
      castellii, Saccharomyces kudriavzevii, Saccharomyces mikatae, and Yarrowia
      lipolytica; and by PCR amplification for other Candida species (Candida
      guilliermondii, Candida krusei, Candida parapsilosis, Candida stellatoidea, and
      Candida tropicalis). The phylogenetic comparative analysis identifies a
      hemiascomycete secondary structure consensus that presents a conserved core in
      all species with variable insertions or deletions. The most significant
      variability is found in C. glabrata P RNA in which three insertions exceeding in
      total 700 nt are present in the Specificity domain. This P RNA is more than twice
      the length of any other homologous P RNAs known in the three domains of life and
      is eight times the size of the smallest. RNase P RNA, therefore, represents one
      of the most diversified noncoding RNAs in terms of size variation and structural
      diversity.

PMID- 15987819
TI  - Cumulus cells accelerate aging of mouse oocytes.
AB  - The role of cumulus cells (CCs) that surround oocytes in maturation, ovulation,
      and fertilization has been extensively studied, yet little is known about their
      role in oocyte aging. Although early studies have shown that when ovulated
      oocytes are aged in vitro displayed similar morphological alterations as those
      aged in vivo, a recent study found that vitro culture of mouse oocytes retarded
      oocyte aging. The objective of this study was to test the hypothesis that CCs
      would accelerate oocyte aging. During in vitro aging with CCs of both in vivo
      matured and in vitro-matured mouse oocytes, activation rates increased, whereas
      the maturation-promoting factor (MPF) activity decreased significantly as during
      in vivo aging of the ovulated oocytes. During aging after denudation of CCs,
      however, activation rates of both in vivo-matured and in vitro-matured oocytes
      remained low and the MPF activity decreased much more slowly compared to that of
      oocytes aged with CCs. Although many oocytes aged in vivo and in vitro with CCs
      showed a partial cortical granule (CG) release, very few cumulus-free oocytes
      released their CGs during in vitro aging. When denuded oocytes were cultured with
      cumulus-oocyte-complexes at a 1:2 ratio or on a CC monolayer, activation rates
      increased, while MPF activity decreased significantly. The results strongly
      suggested that CCs accelerated the aging progression of both in vivo-matured and
      in vitro-matured mouse oocytes.

PMID- 15987817
TI  - Evolutionary conservation of minor U12-type spliceosome between plants and
      humans.
AB  - Splicing of rare, U12-type or AT-AC introns is mediated by a distinct spliceosome
      that assembles from U11, U12, U4atac, U6atac, and U5 snRNPs. Although in human
      cells the protein composition of minor and major snRNPs is similar, differences,
      particularly in U11 and U12 snRNPs, have been recently described. We have
      identified an Arabidopsis U11 snRNP-specific 35K protein as an interacting
      partner of an RS-domain-containing cyclophilin. By using a transient expression
      system in Arabidopsis protoplasts, we show that the 35K protein incorporates into
      snRNP. Oligo affinity selection and glycerol gradient centrifugation revealed
      that the Arabidopsis 35K protein is present in monomeric U11 snRNP and in U11/U12
      di snRNP. The interaction of the 35K protein with Arabidopsis SR proteins
      together with its strong sequence similarity to U1-70K suggests that its function
      in splicing of minor introns is analogous to that of U1-70K. Analysis of
      Arabidopsis and Oryza sativa genome sequences revealed that all U11/U12-di-snRNP
      specific proteins are conserved in dicot and monocot plants. In addition, we have
      identified an Arabidopsis gene encoding the homolog of U4atac snRNA and a second
      Arabidopsis gene encoding U6atac snRNA. Secondary structure predictions indicate
      that the Arabidopsis U4atac is able to form dimeric complexes with both
      Arabidopsis U6atac snRNAs. As revealed by RNaseA/T1 protection assay, the U4atac
      snRNA gene is expressed as an ~160-nt RNA, whereas the second U6atac snRNA gene
      seems to be a pseudogene. Taken together, our data indicate that recognition and
      splicing of minor, AT-AC introns in plants is highly similar to that in humans.

PMID- 15987818
TI  - Vertebrate GLD2 poly(A) polymerases in the germline and the brain.
AB  - Cytoplasmic polyadenylation is important in the control of mRNA stability and
      translation, and for early animal development and synaptic plasticity. Here, we
      focus on vertebrate poly(A) polymerases that are members of the recently
      described GLD2 family. We identify and characterize two closely related GLD2
      proteins in Xenopus oocytes, and show that they possess PAP activity in vivo and
      in vitro and that they bind known polyadenylation factors and mRNAs known to
      receive poly(A) during development. We propose that at least two distinct
      polyadenylation complexes exist in Xenopus oocytes, one of which contains GLD2;
      the other, maskin and Pumilio. GLD2 protein interacts with the polyadenylation
      factor, CPEB, in a conserved manner. mRNAs that encode GLD2 in mammals are
      expressed in many tissues. In the brain, mouse, and human GLD2 mRNAs are abundant
      in anatomical regions necessary for long-term cognitive and emotional learning.
      In the hippocampus, mouse GLD2 mRNA colocalizes with CPEB1 and Pumilio1 mRNAs,
      both of which are likely involved in synaptic plasticity. We suggest that
      mammalian GLD2 poly(A) polymerases are important in synaptic translation, and in
      polyadenylation throughout the soma.

PMID- 15987820
TI  - Role of FOXO1A in the regulation of insulin-like growth factor-binding protein-1
      in human endometrial cells: interaction with progesterone receptor.
AB  - Insulin-like growth factor-binding protein-1 (IGFBP1) is a major secretory
      product of the decidualized endometrium. In the present study, we investigated
      the role of two transcription factors, progesterone receptor (PGR) and a member
      of the forkhead box class O family of transcription factors (FOXO1A), in the
      regulation of the IGFBP1 gene in endometrial cells. Human endometrial fibroblasts
      (HuF) expressed FOXO1A, progesterone receptor A (PGRA), and progesterone receptor
      B (PGRB) proteins, whereas the endometrial adenocarcinoma cell line, HEC-1B
      cells, expressed only FOXO1A and no detectable PGR proteins. When FOXO1A
      expression was silenced using small interference RNA, IGFBP1 expression decreased
      in both HuF and HEC-1B cells. Using the chromatin immunoprecipitation technique,
      we demonstrated that liganded PGR was recruited to the IGFBP1 promoter region (
      358 to -49). In addition, immunoprecipitation of HuF nuclear proteins with a PGR
      antibody followed by immunoblotting with anti-FOXO1A revealed that these two
      proteins interact in these cells. Reporter studies demonstrated that whereas
      liganded PGRA or PGRB increased a progesterone response element-linked reporter
      construct, pPRE/ GRE.E1b.Luc, coexpression of FOXO1A inhibited the PGRB response
      in HuF and synergistically increased PGRA and PGRB response in HEC-1B cells.
      Furthermore, in HEC-1B cells, FOXO1A increased IGFBP1 promoter activity, and
      coexpression of PGRA or PGRB further increased the promoter activity in a
      cooperative manner. In HuF, the response to FOXO1A and PGR was not additive; in
      fact, it was lower than the sum of the individual responses. Thus, FOXO1A and PGR
      associate with one another, and each influences the transactivating potential of
      the other. The cell type-dependent responses strongly implicate the involvement
      of other cofactors.

PMID- 15987821
TI  - Translational regulation of MOS messenger RNA in pig oocytes.
AB  - The temporal and spatial translation control of stored mRNA in oocytes is
      regulated by elements in their 3'-untranslated region (3'-UTR). The MOS 3'-UTR in
      pig oocytes is both heterogeneous (180, 480, or 530 nucleotides), and it contains
      multiple U-rich elements and extensive A-rich sequences (CA13CA5CA5CA6). We have
      examined the role of these potential regulatory elements by fusing wild-type or
      mutant MOS 3'-UTRs to luciferase mRNA and then injecting these chimeric
      transcripts into oocytes. We draw six main conclusions. First, the length of the
      MOS 3'-UTR tightly controls the level of translation of luciferase during oocyte
      maturation. Second, two U-rich (U5A) elements and the hexanucleotide signal
      (AAUAAA) are required for translation. Third, mutations, duplications, or
      relocations of the A-rich sequence reduce or block translation. Fourth, the
      relative importance of the A-rich and U-rich elements in controlling the level of
      translation differs. Fifth, none of our MOS 3'-UTR manipulations relieved
      translational repression before germinal vesicle breakdown. Sixth, all the MOS
      mRNA variants underwent polyadenylation during maturation. Whereas mutations to
      the hexanucleotide signal block both polyadenylation and translation, mutations
      to either the A-rich sequence or the U-rich elements block translation without
      fully blocking polyadenylation. We conclude that MOS mRNA translation in pig
      oocytes is subject to a more extensive series of controls than that in lower
      vertebrates.

PMID- 15987822
TI  - Shedding of the germinal angiotensin I-converting enzyme (gACE) involves a serine
      protease and is activated by epididymal fluid.
AB  - The present report describes how the soluble germinal angiotensin I-converting
      enzyme (gACE) appears in the epididymal fluid, where it has been identified in
      some laboratory rodents and domestic ungulates. We showed that this gACE results
      from an active proteolytic process that releases the enzyme's extracellular
      domain from sperm in a precise spatiotemporal location during epididymal transit
      and that this process involves serine protease activity. Using polyclonal
      antibodies against the C-terminal intracellular sequence of ACE, a fragment of
      approximately 10 kDa was detected on the sperm extract only in the epididymal
      region, where the gACE release occurs. The fluid enzyme was purified, and the
      cleavage site was determined by mass spectrometry to be between Arg622 and Leu623
      of the mature sheep gACE sequence (equivalent to Arg627 and Arg1203 of the human
      mature gACE and somatic ACE sequences, respectively). Thereafter, the C-terminal
      Arg was removed, leaving Ala621 as a C-terminal. Using an in vitro assay, gACE
      cleavage from sperm was strongly increased by the presence of epididymal fluid
      from the release zone, and this increase was inhibited specifically by the serine
      protease-inhibitor AEBSF but not by para-aminobenzamidine. None of the other
      inhibitors tested, such as metallo- or cystein-protease inhibitors, had a similar
      effect on release. It was also found that this process did not involve changes in
      gACE phosphorylation.

PMID- 15987823
TI  - Meiotic messenger RNA and noncoding RNA targets of the RNA-binding protein
      Translin (TSN) in mouse testis.
AB  - In postmeiotic male germ cells, TSN, formerly known as testis brain-RNA binding
      protein, is found in the cytoplasm and functions as a posttranscriptional
      regulator of a group of genes transcribed by the transcription factor CREM-tau.
      In contrast, in pachytene spermatocytes, TSN is found predominantly in nuclei.
      Tsn-null males show a reduced sperm count and high levels of apoptosis in meiotic
      cells, suggesting a critical function for TSN during meiosis. To identify meiotic
      target RNAs that associate in vivo with TSN, we reversibly cross-linked TSN to
      RNA in testis extracts from 17-day-old and adult mice and immunoprecipitated the
      complexes with an affinity-purified TSN antibody. Extracts from Tsn-null mice
      were used as controls. Cloning and sequencing the immunoprecipitated RNAs, we
      identified four new TSN target mRNAs, encoding diazepam-binding inhibitor-like 5,
      arylsulfatase A, a tetratricopeptide repeat structure-containing protein, and
      ring finger protein 139. In contrast to the population of postmeiotic
      translationally delayed mRNAs that bind TSN, these four mRNAs are initially
      expressed in pachytene spermatocytes. In addition, anti-TSN also precipitated a
      nonprotein-coding RNA (ncRNA), which is abundant in nuclei of pachytene
      spermatocytes and has a putative polyadenylation signal, but no open reading
      frame. A second similar ncRNA is adjacent to a GGA repeat, a motif frequently
      associated with recombination hot spots. RNA gel-shift assays confirm that the
      four new target mRNAs and the ncRNA specifically bind to TSN in testis extracts.
      These studies have, for the first time, identified both mRNAs and a ncRNA as TSN
      targets expressed during meiosis.

PMID- 15987824
TI  - Regulation of mouse follicle development by follicle-stimulating hormone in a
      three-dimensional in vitro culture system is dependent on follicle stage and
      dose.
AB  - The developmental requirements of ovarian follicles are dependent on the
      maturation stage of the follicle; in particular, elegant studies with genetic
      models have indicated that FSH is required for antral, but not preantral,
      follicle growth and maturation. To elucidate further the role of FSH and other
      regulatory molecules in preantral follicle development, in vitro culture systems
      are needed. We employed a biomaterials-based approach to follicle culture, in
      which follicles were encapsulated within matrices that were tailored to the
      specific developmental needs of the follicle. This three-dimensional system was
      used to examine the impact of increasing doses of FSH on follicle development for
      two-layered secondary (100-130 microm; two layers of granulosa cells surrounding
      the oocyte) and multilayered secondary (150-180 microm, several layers of
      granulosa cells surrounding the oocyte) follicles isolated from mice. Two-layered
      secondary follicles were FSH responsive when cultured in alginate-collagen I
      matrices, exhibiting FSH dose-dependent increases in follicle growth, lactate
      production, and steroid secretion. Multilayered secondary follicles were FSH
      dependent, with follicle survival, growth, steroid secretion, metabolism, and
      oocyte maturation all regulated by FSH. However, doses greater than 25 mIU/ml of
      FSH negatively impacted multilayered secondary follicle development (reduced
      follicle survival). The present results indicate that the hormonal and
      environmental needs of the follicular complex change during the maturation
      process. The culture system can be adapted to each stage of development, which
      will be especially critical for translation to human follicles that have a longer
      developmental period.

PMID- 15987825
TI  - Differential steroidogenic gene expression in the fetal adrenal gland versus the
      testis and rapid and dynamic response of the fetal testis to di(n-butyl)
      phthalate.
AB  - The phthalate ester di(n-butyl) phthalate (DBP) causes feminization of male rats
      upon in utero exposure by repressing expression of genes required for testicular
      steroidogenesis. Previous work in our laboratory has shown that repression of
      gene expression and steroidogenesis in the fetal testis is apparent within a few
      hours of DBP exposure. The purpose of this study was to determine the precise
      timing of DBP-associated gene expression changes in the fetal testis using
      transcriptional profiling and to determine whether DBP exerts similar effects on
      steroidogenesis in the fetal adrenal. A DBP time-course experiment showed that
      testicular steroidogenesis was decreased within 1 h of DBP exposure and that this
      decrease preceded the repressed transcription of Star (steroidogenic acute
      regulatory protein); Scarb1 (scavenger receptor class B, member 1; also know as
      Sr-b1); Cyp11a1 (cytochrome P450, family 11, subfamily a, polypeptide 1; also
      known as P450SCC); and Cyp17a1 (cytochrome P450 family 17, subfamily a,
      polypeptide 1; also known as Cyp17). Gene expression profiling demonstrated rapid
      (within 1 to 3 h) and transient induction of immediate early genes in the fetal
      testis after administration of DBP to the pregnant dam. There was a statistically
      insignificant decrease in corticosterone production by the fetal adrenal after in
      utero exposure to DBP from Gestation Day 12 to Gestation Day 19. The extent of
      steroidogenesis diminution was much less in the adrenal than in the testis
      (approximately 45% decrease in the adrenal versus 87% decrease in the testis) and
      expression of genes required for steroidogenesis in the adrenal was unaffected by
      DBP. Together, these studies demonstrate that DBP initiates a rapid and dynamic
      change in gene expression in the fetal testis that likely plays a role in the
      reduction in steroidogenesis that is unique to the fetal testis relative to the
      steroidogenically active fetal adrenal.

PMID- 15987826
TI  - Dynamics of microtubules and positioning of female pronucleus during bovine
      parthenogenesis.
AB  - The zygote centrosome, consisting of both paternal and maternal centrosomal
      components, is the microtubule-organizing center necessary for pronuclear
      migration and positioning in fertilization. Maternal centrosomal function in
      microtubule organization and pronuclear positioning, however, remains unclear. In
      the present study, we sought to elucidate the function of maternal centrosomes
      during bovine parthenotes in the microtubule organizational processes required to
      move the pronucleus to the cell center without sperm centrosomal components.
      Microtubule organization, pronuclear position, and distribution of gamma-tubulin,
      which is thought to be the major component of maternal centrosomal material, were
      imaged by immunocytochemistry and conventional epifluorescence microscopy. In
      bovine parthenotes treated with paclitaxel, a microtubule-stabilizing drug, the
      cytoplasmic microtubule asters became organized after chemical activation, and
      the microtubules radiated dynamically toward the female pronucleus. The
      microtubule patterns correlated well with pronuclear movement to the cell center.
      Microtubules aggregated at regions of gamma-tubulin concentration, but gamma
      tubulin did not localize to a spot until the first interphase of bovine
      parthenogenesis. These findings indicate that gamma-tubulin is responsible for
      microtubule organization as the maternal centrosome. In bovine parthenogenesis,
      the maternal centrosome then organizes cytoplasmic microtubules to move the
      female pronucleus into the cell center. We propose that the maternal centrosome
      plays a role as a functional centrosome despite the lack of a sperm contribution,
      making this structure less competent for microtubule organization in comparison
      with centrosomes containing sperm centrosomal components.

PMID- 15987827
TI  - Vascular endothelial growth factor (VEGF) production by the monkey corpus luteum
      during the menstrual cycle: isoform-selective messenger RNA expression in vivo
      and hypoxia-regulated protein secretion in vitro.
AB  - Experiments were designed to investigate the expression and regulation of
      vascular endothelial growth factor (VEGF) in the primate corpus luteum (CL)
      throughout the luteal life span in the natural menstrual cycle. Corpora lutea
      were collected during the early (ECL; Days 3-5 post-LH surge), mid (MCL; Day 6-8
      post-LH surge), mid-late (MLCL; Days 10-12 post-LH surge), late (LCL; Days 14-16
      post-LH surge), and very late (Days 17- 18 post-LH surge) luteal phase. Specific
      primers were designed to amplify mRNAs encoding VEGF isoforms 206, 189, 183, 165,
      145, and 121. Only two cDNA products were obtained by reverse transcription
      polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends; cloning
      and sequencing confirmed their 98% homology to the corresponding human VEGF 165
      and 121 sequences. Semiquantitative RT-PCR assays indicated that VEGF 165 mRNA
      levels increased (P < 0.05) from ECL to MLCL but then declined (P < 0.05) by LCL.
      Although VEGF 121 mRNA levels were limited in ECL, they increased significantly
      in MCL (P < 0.05). Levels of VEGF protein, as measured by Western blot analysis,
      were two- to fourfold higher for VEGF 165 versus VEGF 121. Also, VEGF 165 levels
      were higher (P < 0.05) in ECL and MCL compared to those at later stages. During 2
      day culture, preparations of dispersed luteal cells secreted VEGF into the media;
      the highest levels were observed in ECL and declined (P < 0.05) by LCL.
      Regardless of luteal stage, hypoxic conditions increased (P < 0.05) VEGF levels,
      whereas LH exposure increased (P < 0.05) progesterone, but not VEGF, in the
      media. These results are consistent with a dynamic, local regulation of VEGF
      production during the life span of the primate CL that is not directly controlled
      by LH.

PMID- 15987828
TI  - Chronic morphine up-regulates G alpha12 and cytoskeletal proteins in Chinese
      hamster ovary cells expressing the cloned mu opioid receptor.
AB  - A growing body of literature indicates that chronic morphine exposure alters the
      expression and function of cytoskeletal proteins in addition to the well
      established interactions between mu opioid receptors and G proteins. In the
      present study, we hypothesized that chronic morphine alters the expression and
      functional effects of G alpha12, a G protein that regulates downstream
      cytoskeletal proteins via its control of RhoA. Our results showed that chronic
      morphine treatment decreased the expression of G alpha i2 (64%) and G alpha i3
      (60%), had no effect of G alpha o, and increased G alpha12 (66%) expression in
      Chinese hamster ovary (CHO) cells expressing the cloned human mu opioid receptors
      (hMOR-CHO cells) but not in cells expressing a mutant mu opioid receptor that do
      not develop morphine tolerance and dependence (T394A-CHO cells). Morphine
      treatment had no significant effect on PAR-1 thrombin receptor-activated G
      protein activity, as measured by thrombin-stimulated guanosine 5'-O-(3
      [35S]thio)triphosphate binding. Chronic morphine treatment significantly enhanced
      thrombin-stimulated RhoA activity and thrombin-stimulated expression of alpha
      actinin, a cytoskeletal anchoring protein, in hMOR-CHO cells. Proteomic analysis
      of two-dimensional gel spots prepared from hMOR-CHO cells showed that morphine
      treatment affected the expression of a number of proteins associated with
      morphological changes. Up-regulation of G alpha12 and alpha-actinin by chronic
      morphine was also observed in mouse brain. Viewed collectively, these findings
      indicate, for the first time, that chronic morphine enhances the G alpha12
      associated signaling system, which is involved in regulating cellular morphology
      and growth, supporting other findings that chronic morphine may alter cellular
      morphology, in addition to cellular function.

PMID- 15987829
TI  - Neurotensin-deficient mice have deficits in prepulse inhibition: restoration by
      clozapine but not haloperidol, olanzapine, or quetiapine.
AB  - Prepulse inhibition (PPI) of the acoustic startle reflex is a commonly used
      measure of preattentive sensorimotor gating. Disrupted PPI in rodents represents
      an animal model of the sensorimotor gating deficits characteristic of
      schizophrenia. The neurotensin (NT) system is implicated in the pathophysiology
      of schizophrenia, and NT has been hypothesized to act as an endogenous
      antipsychotic. In rats, NT receptor agonists restore PPI disrupted by dopamine
      receptor agonists and N-methyl-D-aspartate receptor antagonists, and pretreatment
      with an NT receptor antagonist blocks restoration of isolation rearing induced
      deficits in PPI by some antipsychotic drugs. The current studies further
      scrutinized the role of the NT system in the regulation of PPI and in
      antipsychotic drug-induced restoration of PPI using NT-null mutant mice (NT-/-).
      NT-/- mice exhibited significantly higher pulse alone startle amplitudes and
      disrupted PPI compared with NT+/+ mice. Haloperidol (0.1 mg/kg) and quetiapine
      (0.5 mg/kg) administered 30 min before PPI testing significantly increased PPI in
      NT+/+ mice but had no effect on PPI in NT-/- mice. In contrast, clozapine (1.0
      mg/kg) significantly increased PPI in both NT-/- and NT+/+ mice, whereas
      olanzapine (0.5 mg/kg) had no effect on PPI in either NT-/- or NT+/+ mice. In a
      separate experiment, amphetamine (2.0 mg/kg i.p.) significantly disrupted PPI in
      NT+/+ mice but not NT-/- mice. These results provide evidence that the effects of
      antipsychotic drugs (APDs) may be differentially affected by the state of NT
      neurotransmission and, moreover, that APDs differ in their dependence on an
      intact NT system.

PMID- 15987830
TI  - Dieldrin induces ubiquitin-proteasome dysfunction in alpha-synuclein
      overexpressing dopaminergic neuronal cells and enhances susceptibility to
      apoptotic cell death.
AB  - Exposure to pesticides is implicated in the etiopathogenesis of Parkinson's
      disease (PD). The organochlorine pesticide dieldrin is one of the environmental
      chemicals potentially linked to PD. Because recent evidence indicates that
      abnormal accumulation and aggregation of alpha-synuclein and ubiquitin-proteasome
      system dysfunction can contribute to the degenerative processes of PD, in the
      present study we examined whether the environmental pesticide dieldrin impairs
      proteasomal function and subsequently promotes apoptotic cell death in rat
      mesencephalic dopaminergic neuronal cells overexpressing human alpha-synuclein.
      Overexpression of wild-type alpha-synuclein significantly reduced the proteasomal
      activity. Dieldrin exposure dose-dependently (0-70 microM) decreased proteasomal
      activity, and 30 microM dieldrin inhibited activity by more than 60% in alpha
      synuclein cells. Confocal microscopic analysis of dieldrin-treated alpha
      synuclein cells revealed that alpha-synuclein-positive protein aggregates
      colocalized with ubiquitin protein. Further characterization of the aggregates
      with the autophagosomal marker mondansyl cadaverine and the lysosomal marker and
      dot-blot analysis revealed that these protein oligomeric aggregates were distinct
      from autophagosomes and lysosomes. The dieldrin-induced proteasomal dysfunction
      in alpha-synuclein cells was also confirmed by significant accumulation of
      ubiquitin protein conjugates in the detergent-insoluble fraction. We found that
      proteasomal inhibition preceded cell death after dieldrin treatment and that
      alpha-synuclein cells were more sensitive than vector cells to the toxicity.
      Furthermore, measurement of caspase-3 and DNA fragmentation confirmed the
      enhanced sensitivity of alpha-synuclein cells to dieldrin-induced apoptosis.
      Together, our results suggest that increased expression of alpha-synuclein
      predisposes dopaminergic cells to proteasomal dysfunction, which can be further
      exacerbated by environmental exposure to certain neurotoxic compounds, such as
      dieldrin.

PMID- 15987831
TI  - Distribution of the novel antifolate pemetrexed to the brain.
AB  - Pemetrexed disodium is a novel antifolate that exhibits potent inhibitory effects
      on multiple enzymes in folate metabolism. Phase II/III clinical trials have shown
      that pemetrexed is effective against various solid tumors. Like methotrexate,
      pemetrexed may be useful in treatment of primary and secondary brain tumors. In
      this study, we examined the central nervous system (CNS) distribution of
      pemetrexed and the interaction with an organic anion transport inhibitor
      indomethacin. Male Wistar rats were administered pemetrexed by either single
      intravenous bolus or constant intravenous infusion. Unbound pemetrexed in blood
      and brain was measured by simultaneous arterial blood and frontal cortex
      microdialysis sampling. In the i.v. bolus experiments, indomethacin was
      administered by i.v. bolus (10 mg/kg) followed by i.v. infusion (0.1 mg/kg/h) in
      a crossover manner. In the infusion experiments, the same dose of indomethacin
      was administered after a steady state was reached for pemetrexed. CNS
      distributional kinetics was analyzed by compartmental and noncompartmental
      methods. Both bolus and infusion studies showed that pemetrexed has a limited CNS
      distribution. The mean area under concentration-time curve
      (AUC)(brain)/AUC(plasma) ratio of unbound pemetrexed was 0.078 +/- 0.038 in the
      i.v. bolus study. The pemetrexed steady-state brain-to-plasma unbound
      concentration ratio after i.v. infusion was 0.106 +/- 0.054. The distributional
      clearance into the brain was approximately 10% of the clearance out of the brain
      in both the compartmental and noncompartmental analyses. Indomethacin had no
      effect on either the brain-to-plasma AUC ratio or the steady-state brain-to
      plasma concentration ratio. The distribution of pemetrexed into the brain is
      limited, and an efflux clearance process, such as an efflux transporter, may be
      involved.

PMID- 15987832
TI  - Role and relevance of peptide transporter 2 (PEPT2) in the kidney and choroid
      plexus: in vivo studies with glycylsarcosine in wild-type and PEPT2 knockout
      mice.
AB  - The strategic localization of peptide transporter 2 (PEPT2), a proton-coupled
      oligopeptide transporter, to the apical membrane of epithelial cells in the
      kidney and choroid plexus suggests that it plays an important role in the
      disposition of peptides/mimetics in the body. Therefore, the in vivo significance
      of PEPT2 was investigated in wild-type and PEPT2 null mice following an i.v.
      bolus dose (0.05 micromol/g body weight) of [14C]glycylsarcosine (GlySar). In
      PEPT2 null mice, the clearance (total and renal) of GlySar was markedly increased
      (2-fold), resulting in concomitantly lower systemic concentrations. In addition,
      renal reabsorption was almost abolished, and GlySar was eliminated by glomerular
      filtration. Of the 46% of GlySar reabsorbed in wild-type mice, PEPT2 accounted
      for 86% and PEPT1 accounted for 14% of reabsorbed substrate. Analysis of GlySar
      uptake in kidney sections revealed that PEPT2 was primarily localized in the
      outer medullary region. Wild-type mice also had greater choroid plexus
      concentrations of GlySar and a 5-fold greater choroid plexus/cerebrospinal fluid
      (CSF) ratio as compared with null mice at 60 min. Null mice exhibited a greater
      CSF/blood ratio at 60 min (0.9 versus 0.2) and area under the curve
      (AUC)(CSF)/AUC(blood) ratio over 60 min (0.45 versus 0.12), indicating that PEPT2
      significantly reduces the exposure of GlySar in CSF. Our in vivo results
      demonstrate that PEPT2 is the predominant peptide transporter in kidney and that
      it acts as an efflux transporter in choroid plexus. Thus, PEPT2 may have profound
      effects on the sensitivity and/or toxicity of peptides and peptide-like drugs.

PMID- 15987833
TI  - The para substituent of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3
      trifluoromethyl-phenyl)-propionamides is a major structural determinant of in
      vivo disposition and activity of selective androgen receptor modulators.
AB  - Selective androgen receptor modulators (SARMs) have many potential therapeutic
      applications, including male hypogonadism, osteoporosis, muscle-wasting diseases,
      sexual libido, and contraception. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N
      (4-nitro-3-trifluoromethyl-phenyl)-propionamides bearing a four-halogen
      substituent in the B-ring that displayed in vivo activity were identified in our
      previous study. Interestingly, in vivo pharmacological activity was not
      correlated with in vitro androgen receptor (AR) binding affinity. In this study,
      analysis of the area under the concentration-time curve-response relationship
      demonstrated that the discrepancy between in vitro and in vivo pharmacological
      activity of these halogen-substituted SARMs was due to differences in systemic
      exposure rather than intrinsic pharmacological activity. Studies also suggested
      that two simple criteria (i.e., Ki < 10 nM and lower in vivo clearance) could be
      used to identify efficacious and potent SARMs. We tested this hypothesis using a
      series of four compounds incorporating either a nitro or cyano substituent at the
      para-position of the A- and B-aromatic rings. The S-3-(4-nitrophenoxy) and S-3-(4
      cyanophenoxy) 2-hydroxy-2-methyl-N-(4-nitro-3-trifluromethylphenyl) propionamides
      (S-19 and S-20, respectively) and S-3-(4-nitrophenoxy) and S-3-(4-cyanophenoxy) 2
      hydroxy-2-methyl-N-(4-cyano-3-trifluromethylphenyl) propionamides (S-21 and S-22,
      respectively) demonstrated high AR binding affinity, with Ki values ranging from
      2.0 to 3.8 nM. Pharmacokinetic studies of selected compounds showed that the in
      vivo clearance of S-22 was the slowest followed sequentially by S-20, S-21, and S
      19. The dose-response relationships for S-22 showed that S-22 exerted efficacious
      and selective activity in anabolic tissues at dose rates as low as 0.03 mg/day,
      indicative of the high potency of this compound in anabolic tissue (relative
      potency 4.41) and its potential for clinical use in androgen deficiency-related
      disorders.

PMID- 15987834
TI  - Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to
      neurochemical profile of novel antipsychotics: frontocortical dopamine and
      hippocampal serotonin release in rat brain.
AB  - Several novel antipsychotics, such as aripiprazole, bifeprunox, SSR181507 [(3
      exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8
      azabicyclo(3.2.1)octane-3-methanamine], and SLV313 [1-(2,3-dihydro
      benzo[1,4]dioxin-5-yl)-4-[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-piperazine],
      activate serotonin 5-hydroxytryptamine (5-HT)1A receptors. Such activity is
      associated with enhanced treatment of negative symptoms and cognitive deficits,
      which may be mediated by modulation of cerebral dopamine and serotonin levels. We
      employed microdialysis coupled to high pressure liquid chromatography with
      electrochemical detection to examine 5-HT1A receptor activation in the modulation
      of extracellular dopamine in medial prefrontal cortex and serotonin in
      hippocampus of freely moving rats. The above compounds were compared with drugs
      that have less interaction with 5-HT1A receptors (clozapine, nemonapride,
      ziprasidone, olanzapine, risperidone, and haloperidol). Hippocampal 5-HT was
      decreased by bifeprunox, SSR181507, SLV313, sarizotan, and nemonapride, effects
      similar to those seen with the 5-HT1A agonist, (+)-8-hydroxy-2-(di-n
      propylamino)tetralin [(+)8-OH-DPAT], consistent with activation of 5-HT1A
      autoreceptors. These decreases were reversed by the selective 5-HT1A antagonist,
      WAY100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl)cyclohexanecarboxamide]. In contrast, haloperidol, risperidone,
      clozapine, olanzapine, ziprasidone, and aripiprazole did not significantly modify
      hippocampal serotonin levels. In medial prefrontal cortex, dopamine levels were
      increased by SSR181507, SLV313, sarizotan, and (+)8-OH-DPAT. These effects were
      reversed by WAY100635, indicating mediation by 5-HT1A receptors. In contrast, the
      increases in dopamine levels induced by clozapine, risperidone, olanzapine, and
      ziprasidone were not blocked by WAY100635, consistent with predominant influence
      of other mechanisms in the actions of these drugs. Haloperidol, nemonapride, and
      the D2 partial agonists, aripiprazole and bifeprunox, did not significantly alter
      dopamine release. Taken together, these data demonstrate the diverse contribution
      of 5-HT1A receptor activation to the profile of antipsychotics and suggest that
      novel drugs selectively targeting D2 and 5-HT1A receptors may present distinctive
      therapeutic properties.

PMID- 15987836
TI  - Nutritional and functional importance of intestinal sulfur amino acid metabolism.
AB  - The metabolism of sulfur amino acids, methionine and cysteine, has been linked to
      several key aspects of human health and cellular function. In addition, the
      metabolism of dietary amino acids by the gastrointestinal tract is nutritionally
      important for normal function. In the case of sulfur amino acids (SAAs), in vivo,
      stable isotope studies in adults suggest that the splanchnic tissues utilize as
      much as 30-44% of the dietary methionine and cysteine. Similarly, the dietary
      methionine requirement is 30% lower in total parenteral nutrition (TPN)-fed
      piglets, a condition in which dietary nutrients largely bypass intestinal
      metabolism. These data suggest that intestinal metabolism of methionine is
      substantial, yet the intestinal metabolic fate of dietary methionine is largely
      unknown. Dietary cysteine likely plays a key role in intestinal epithelial
      antioxidant function as a precursor for glutathione. Moreover, cysteine and
      glutathione may also regulate epithelial cell proliferation via modulation of
      redox status. Recent evidence indicates that transformed colonic epithelial cells
      are capable of methionine transmethylation and transsulfuration. This review
      discusses the evidence of intestinal SAA metabolism and how this affects nutrient
      requirements and epithelial function.

PMID- 15987837
TI  - The nutritional phenotype in the age of metabolomics.
AB  - The concept of the nutritional phenotype is proposed as a defined and integrated
      set of genetic, proteomic, metabolomic, functional, and behavioral factors that,
      when measured, form the basis for assessment of human nutritional status. The
      nutritional phenotype integrates the effects of diet on disease/wellness and is
      the quantitative indication of the paths by which genes and environment exert
      their effects on health. Advances in technology and in fundamental biological
      knowledge make it possible to define and measure the nutritional phenotype
      accurately in a cross section of individuals with various states of health and
      disease. This growing base of data and knowledge could serve as a resource for
      all scientific disciplines involved in human health. Nutritional sciences should
      be a prime mover in making key decisions that include: what environmental inputs
      (in addition to diet) are needed; what genes/proteins/metabolites should be
      measured; what end-point phenotypes should be included; and what informatics
      tools are available to ask nutritionally relevant questions. Nutrition should be
      the major discipline establishing how the elements of the nutritional phenotype
      vary as a function of diet. Nutritional sciences should also be instrumental in
      linking the elements that are responsive to diet with the functional outcomes in
      organisms that derive from them. As the first step in this initiative, a
      prioritized list of genomic, proteomic, and metabolomic as well as functional and
      behavioral measures that defines a practically useful subset of the nutritional
      phenotype for use in clinical and epidemiological investigations must be
      developed. From this list, analytic platforms must then be identified that are
      capable of delivering highly quantitative data on these endpoints. This
      conceptualization of a nutritional phenotype provides a concrete form and
      substance to the recognized future of nutritional sciences as a field addressing
      diet, integrated metabolism, and health.

PMID- 15987838
TI  - Commentary on: tissue distribution of quercetin in rats and pigs.

PMID- 15987839
TI  - D-lactate in human and ruminant metabolism.
AB  - D-lactate is normally present in the blood of mammals at nanomolar concentrations
      due to methylglyoxal metabolism; millimolar d-lactate concentrations can arise
      due to excess gastrointestinal microbial production. Grain overload in ruminants,
      short-bowel syndrome in humans, and diarrhea in calves can all result in profound
      D-lactic acidemia, with remarkably similar neurological manifestations. In the
      past, D-lactate was thought to be excreted mainly in the urine, and metabolized
      slowly by the enzyme d-alpha-hydroxy acid dehydrogenase. More recent studies
      reported that mammals have a relatively high capacity for D-lactate metabolism
      and identified a putative mammalian D-lactate dehydrogenase. A growing body of
      literature is also emerging describing subclinical elevation of D-lactate as an
      indicator of sepsis and trauma. This article describes advances in the
      understanding of D-lactate metabolism, D-lactic acidosis in ruminants and humans,
      and subclinical elevation of d-lactate.

PMID- 15987840
TI  - Uptake of micellar long-chain fatty acid and sn-2-monoacylglycerol into human
      intestinal Caco-2 cells exhibits characteristics of protein-mediated transport.
AB  - Long-chain fatty acid and sn-2-monoacylglycerol (2-MG) are the digestive products
      of dietary triacylglycerol (TG) hydrolysis. Although fatty acid uptake into the
      enterocyte has been examined widely, less is known about 2-MG uptake, and few
      studies have mimicked the physiologic conditions present in the postprandial
      situation. In this study, the cellular uptake of oleic acid and 2-monoolein,
      presented in taurocholate micellar solution, was examined in human intestinal
      Caco-2 cells to model the postprandial intestinal milieu. Initial uptake of oleic
      acid and 2-MG displayed a saturable function of their monomer concentrations,
      suggesting that fatty acid and 2-MG uptake may be protein-mediated processes at
      low unbound concentrations of lipid. The initial rate of oleate uptake was faster
      and the apparent Km was lower than values for 2-MG. Unlabeled oleic acid and, to
      a lesser extent, unlabeled 2-MG, inhibited the uptakes of both [3H]oleic acid and
      [3H]2-monoolein, suggesting competitive uptake. The nonphysiologic isomer sn-1-MG
      had effects similar to 2-MG, whereas the intermediate digestive product,
      diacylglycerol (DG), did not inhibit either oleate or 2-monoolein uptake. These
      results suggest that in the postprandial state, fatty acid and 2-MG derived from
      dietary TG are transported into the enterocyte, at least in part, via a protein
      mediated pathway that is shared by both lipids, but not by the intermediate
      digestive product, DG.

PMID- 15987841
TI  - Soy protein isolate increases hepatic thyroid hormone receptor content and
      inhibits its binding to target genes in rats.
AB  - Our previous studies showed that intake of 20% alcohol-washed soy protein isolate
      (SPI) significantly increased hepatic thyroid hormone receptor (TR) beta1 protein
      content in rats. However, whether SPI influences the binding ability of TR to its
      target genes is unknown. The purpose of this study was to examine the effect of
      increasing amounts of dietary SPI on hepatic TRbeta1 content and the binding of
      TR to thyroid hormone response element (TRE) in rats. Sprague-Dawley rats (28 d
      old) were fed diets containing casein (20%) with or without isoflavone
      supplementation (50 mg/kg diet) or alcohol-washed SPI (5, 10, or 20%) for 90 d.
      The hepatic TRbeta1 protein content was measured by Western blot, and the binding
      ability of TR to DNA was examined by electrophoretic mobility shift assay.
      Consumption of the 20% SPI diet increased pancreatic relative weight and
      decreased spleen relative weight. Intake of SPI markedly elevated TRbeta1 content
      in both male and female rats compared with a casein-based control diet. The
      increase in TRbeta1 in females was much higher than that in males. Interestingly,
      the binding abilities of TR to DNA were significantly inhibited by increasing
      amounts of dietary SPI in female rats. In conclusion, this study shows for the
      first time that dietary SPI increases hepatic TRbeta1 protein content and
      inhibits the binding of TR to target genes. Modulation of hepatic TRbeta1, a key
      regulator of gene expression involved in lipid metabolism, by SPI may be a novel
      mechanism by which soy components lower blood lipid level and exert their
      hypocholesterolemic actions.

PMID- 15987842
TI  - Impairment of VLDL secretion by medium-chain fatty acids in chicken primary
      hepatocytes is affected by the chain length.
AB  - To determine the effect of the chain length of medium-chain fatty acids (MCFAs)
      on VLDL secretion, the media of chicken hepatocyte cultures were supplemented
      with hexanoate (6:0), octanoate (8:0), decanoate (10:0), or dodecanoate (12:0).
      The supplementation of palmitate (16:0) or bovine serum albumin (BSA) alone in
      media was used as the positive control or the control, respectively. Palmitate
      significantly increased intracellular triacylglycerol (TG) accumulation and VLDL
      TG, -cholesterol, and -apolipoprotein (apo)B secretion. On the other hand, the
      addition of hexanoate did not affect these variables relative to control cultures
      supplemented with BSA alone, whereas octanoate, decanoate, and dodecanoate
      decreased apoB secretion from the chicken hepatocytes. ApoB secretion from
      hepatocytes cultured with 1.0 mmol/L MCFA, in particular decanoate and
      dodecanoate, in the presence of 0.2 mmol/L palmitate was significantly lower than
      that obtained with 0.2 mmol/L palmitate alone. Decanoate at 0.25-1.0 mmol/L dose
      dependently reduced apoB mRNA expression compared with the control (BSA alone).
      The levels of 3-hydroxy-3-metylglutaryl-CoA reductase and apoA-I mRNA were
      significantly lower in cultures supplemented with hexanoate, octanoate, and
      decanoate than in cultures with dodecanoate and palmitate. These changes did not
      correspond to the reduction in VLDL-apoB secretion. We suggest that MCFAs with
      different chain lengths differentially affect apoB secretion and mRNA expression,
      with decanoate being the most effective at decreasing VLDL-apoB secretion by
      regulating apoB mRNA expression at the transcriptional level.

PMID- 15987843
TI  - Fructose selectively modulates c-jun N-terminal kinase activity and insulin
      signaling in rat primary hepatocytes.
AB  - Fructose is a unique nutrient, due in part to its selective metabolism in the
      liver. Diets enriched in fructose or sucrose induce a hepatic stress response
      characterized by activation of c-jun N-terminal kinase. The aim of this study was
      to examine the regulation of c-jun N-terminal kinase by fructose in rat primary
      hepatocytes. Fructose was provided to rat primary hepatocytes using a fructose
      regenerating system, consisting of inulin and inulinase. This system provides a
      more physiologic delivery of fructose and avoids large disturbances in hepatocyte
      ATP concentrations. Fructose delivery increased c-jun N-terminal kinase activity
      and serine 307 phosphorylation of insulin receptor substrate-1 and reduced
      tyrosine phosphorylation of insulin receptor substrate-1. Activation of c-jun N
      terminal kinase was maximal at a fructose concentration of 0.6 mmol/L. Fructose
      delivery did not increase the phosphorylation of p38 mitogen-activated protein
      kinase, extracellular signal regulated kinase, c-jun, or activating transcription
      factor-2, the latter 2 downstream nuclear targets of c-jun N-terminal kinase.
      However, fructose delivery increased the phosphorylation of mitogen-activated
      protein kinase kinase-7 (MKK7), an upstream activator of c-jun N-terminal kinase,
      and the association of c-jun N-terminal kinase with c-jun N-terminal kinase
      interacting protein-1, a scaffold protein that can sequester protein signaling
      complexes in the cytosol. These data suggest that fructose may selectively
      activate c-jun N-terminal kinase via regulation of MKK7 and scaffold proteins.

PMID- 15987844
TI  - All-trans retinoic acid antagonizes the action of calciferol and its active
      metabolite, 1,25-dihydroxycholecalciferol, in rats.
AB  - An antagonistic interaction between retinol and calciferol has been established.
      However, the mechanism by which this antagonism occurs is unclear. One
      possibility is that retinol affects the metabolism of calciferol. To investigate
      this hypothesis, retinol- and calciferol-depleted rats were given various amounts
      of ergocalciferol, cholecalciferol, 1alpha,25-dihydroxycholecalciferol
      [1,25(OH)2D3], or 24,24-difluoro-1alpha,25-dihydroxycholecalciferol [24-F2
      1,25(OH)2D3] in combination with various amounts of retinyl acetate or all-trans
      retinoic acid (ATRA) in a series of studies. Rats administered 1720 or 3440
      microg retinyl acetate once every 3 d for 33 d in combination with 25.8 ng
      ergocalciferol or 25 ng cholecalciferol every 3 d had lower serum calcium and
      greater serum phosphorus concentrations than rats fed 0 or 11.4 mug retinyl
      acetate every 3 d. In addition, rats fed 400 microg ATRA/d in combination with
      25.8 ng ergocalciferol every 3 d, 25 ng cholecalciferol every 3 d, 2-5 ng
      1,25(OH)2D3/d, or 0.5-1 ng 24-F2-1,25(OH)2D3/d had significantly lower serum
      calcium and higher serum phosphorus concentrations than rats not given ATRA in
      the diet. Therefore, both retinyl acetate and ATRA are able to antagonize the
      action of ergocalciferol and cholecalciferol in vivo. Additionally, ATRA
      antagonizes the in vivo action of 1,25(OH)2D3 and an analog, 24-F2-1,25(OH)2D3,
      that cannot be 24-hydroxylated. Together, these results suggest that retinol does
      not antagonize the action of calciferol by altering the metabolism of calciferol
      or 1,25(OH)2D3, but does so by another mechanism.

PMID- 15987845
TI  - Spray-dried porcine plasma reduces the effects of staphylococcal enterotoxin B on
      glucose transport in rat intestine.
AB  - We investigated the intestinal transport of D-glucose (D-Glc) and 3 essential
      amino acids in a model of intestinal inflammation, and the effects of dietary
      supplementation with animal plasma proteins on this function. Wistar Lewis rats
      were fed a diet containing an isonitrogenous amount of milk protein (control
      group) or a diet supplemented with either spray-dried animal plasma (SDAP) or
      immunoglobulin concentrate (IC) from porcine plasma, from d 21 of life (weaning)
      until d 35. On d 30 and 33, rats were challenged intraperitoneally with
      Staphylococcus aureus enterotoxin B (SEB; groups SEB, SEB-SDAP, and SEB-IC) and
      on d 35, brush border membrane vesicles (BBMVs) were prepared and used for
      transport and binding studies. Administration of SEB reduced D-Glc transport
      across sodium glucose transporter 1 [SGLT1; 20% reduction in maximal transport
      rate (Vmax); P < 0.05], without affecting the Michaelis constant (Km). The
      results from specific phlorizin binding, Western blot, and immunohistochemistry
      supported the view that the effects of SEB are due to reduced expression of D-Glc
      transporters in the apical membrane. SEB increased the passive diffusion constant
      (Kd) for D-Glc 3-fold (P < 0.05). SEB did not affect mediated or passive amino
      acid fluxes of L-leucine, L-methionine, or L-lysine. Dietary SDAP increased the D
      Glc Vmax in the SEB group without affecting the passive component. Changes in d
      Glc Vmax due to SEB and to the dietary treatments were correlated with changes in
      the number of SGLT1 transporters present in the BBMVs (r = 0.9468; P < 0.05).
      Dietary IC had no observed effect. We estimate that, in rats challenged with SEB,
      SDAP supplementation can increase glucose absorption by 8-9% during the
      interdigestive periods.

PMID- 15987846
TI  - High-throughput immunoblotting identifies biotin-dependent signaling proteins in
      HepG2 hepatocarcinoma cells.
AB  - Biotin affects the abundance of mRNA coding for approximately 10% of genes
      expressed in human-derived hepatocarcinoma (HepG2) cells. Here, we determined
      whether effects of biotin on gene expression are associated with changes in the
      abundance of distinct proteins in cell signaling and structure. HepG2 cells were
      cultured in media containing the following concentrations of biotin: 0.025 nmol/L
      (denoted "deficient"), 0.25 nmol/L ("physiological" = control), and 10 nmol/L
      ("pharmacological") for 10 d before harvesting. The abundance of 1009 proteins
      from whole-cell extracts was quantified by using high-throughput immunoblots. The
      abundance of 44 proteins changed by at least 25% in biotin-deficient and biotin
      supplemented cells compared with physiological controls. One third of these
      proteins participate in cell signaling. Specifically, proteins associated with
      receptor tyrosine kinase-mediated signaling were identified as targets of biotin;
      the abundance of these proteins was greater in biotin-deficient cells than in
      controls. This was associated with increased DNA-binding activities of the
      transcription factors Fos and Jun, and increased expression of a reporter gene
      driven by activator protein (AP)1-binding elements in biotin-deficient cells
      compared with physiological controls. The abundance of selected signaling
      proteins was not paralleled by the abundance of mRNA, suggesting that biotin
      affects expression of these genes at a post-transcriptional step. Additional
      clusters of biotin-responsive proteins were identified that play roles in
      cytoskeleton homeostasis, nuclear structure and transport, and neuroscience. This
      study is consistent with the existence of clusters of biotin-responsive proteins
      in distinct biological processes, including signaling by Fos/Jun; the latter
      might mediate the proinflammatory and antiapoptotic effects of biotin deficiency.

PMID- 15987847
TI  - Insulin-like growth factor II and binding proteins 1 and 3 from second trimester
      human amniotic fluid are associated with infant birth weight.
AB  - The developing fetus begins to swallow amniotic fluid (AF) early in gestation, a
      process that results in ingestion of numerous growth factors. Our objectives were
      2-fold: 1) to assess the concentration and distribution of insulin-like growth
      factor II (IGF II) and its binding proteins (BP) 1 and 3 in 2nd trimester
      amniotic fluid using ELISA, and 2) to establish whether concentrations of AF IGF
      II and its binding proteins IGF BP1 and 3, measured early in pregnancy, were
      associated with and predictive of infant birth weight. Birth weights were
      categorized using recently developed birth-weight-for-gestational-age percentiles
      for fetal growth in which infants < 10% were classified as SGA (small-for
      gestational-age) and those > 90% as LGA (large-for-gestational-age). AF samples
      were collected after routine genetic testing (15.1 +/- 0.04 wk, range 12-20 wk)
      from 543 mother-infant pairs in Montreal, QC, Canada. Maternal and fetal
      characteristics were obtained from questionnaires and medical chart review.
      Multivariate regression analysis that controlled for maternal height,
      prepregnancy weight, smoking behavior, infant gender, gestational age, parity, as
      well as amniocentesis week showed that higher AF IGF BP1 was associated with
      lower birth weight (partial r2 = 0.0062). Regression analyses revealed that AF
      IGF BP3 was positively associated with birth weight within LGA and macrosomia
      subpopulations (partial r2 = 0.0283 and 0.0404, respectively). These results show
      that 2nd trimester AF IGF BP1, BP3, and IGF II may emerge as early indicators of
      fetal growth.

PMID- 15987848
TI  - Ascorbate increases human oxaluria and kidney stone risk.
AB  - Currently, the recommended upper limit for ascorbic acid (AA) intake is 2000
      mg/d. However, because AA is endogenously converted to oxalate and appears to
      increase the absorption of dietary oxalate, supplementation may increase the risk
      of kidney stones. The effect of AA supplementation on urinary oxalate was studied
      in a randomized, crossover, controlled design in which subjects consumed a
      controlled diet in a university metabolic unit. Stoneformers (n = 29; SF) and age
      and gender-matched non-stoneformers (n = 19; NSF) consumed 1000 mg AA twice each
      day with each morning and evening meal for 6 d (treatment A), and no AA for 6 d
      (treatment N) in random order. After 5 d of adaptation to a low-oxalate diet,
      participants lived for 24 h in a metabolic unit, during which they were given 136
      mg oxalate, including 18 mg 13C2 oxalic acid, 2 h before breakfast; they then
      consumed a controlled very low-oxalate diet for 24 h. Of the 48 participants, 19
      (12 stoneformers, 7 non-stoneformers) were identified as responders, defined by
      an increase in 24-h total oxalate excretion > 10% after treatment A compared with
      N. Responders had a greater 24-h Tiselius Risk Index (TRI) with AA
      supplementation (1.10 +/- 0.66 treatment A vs. 0.76 +/- 0.42 treatment N) because
      of a 31% increase in the percentage of oxalate absorption (10.5 +/- 3.2%
      treatment A vs. 8.0 +/- 2.4% treatment N) and a 39% increase in endogenous
      oxalate synthesis with treatment A than during treatment N (544 +/- 131 A vs. 391
      +/- 71 micromol/d N). The 1000 mg AA twice each day increased urinary oxalate and
      TRI for calcium oxalate kidney stones in 40% of participants, both stoneformers
      and non-stoneformers.

PMID- 15987849
TI  - Cholesterol metabolism is affected by calcium phosphate supplementation in
      humans.
AB  - Dietary calcium and phosphate precipitate in the small intestine to form
      insoluble amorphous calcium phosphate (ACP). The ability of ACP to bind and
      inactivate luminal bile acids might have an effect on cholesterol metabolism. To
      test this hypothesis, a placebo-controlled, double-blind, crossover study with
      pentacalcium hydroxy-triphosphate supplementation (CaP; 1.0 g elemental calcium)
      was conducted in 31 young healthy volunteers. The CaP was incorporated into
      bread. Serum cholesterol concentrations were lower after 4 wk of supplementation
      than after 4 wk of placebo (4.36 vs. 4.60 mmol/L; P = 0.008). Serum LDL
      cholesterol and the ratio of LDL:HDL cholesterol also tended to be lower after
      CaP supplementation than after placebo (-5.6%, P = 0.083 and -5.4%, P < 0.062,
      respectively). The participants' fat and cholesterol intakes and fecal fat
      excretion did not differ in the 2 periods. Although the analysis of fecal samples
      showed no difference in the excretion of total neutral sterols (sum of
      cholesterol and its transformation products), the excretion of cholesterol itself
      increased (9.64 vs. 5.80 micromol/g dry matter; P = 0.025; n = 25), whereas the
      excretion of the metabolite coprostanol decreased (18.5 vs. 21.0 mumol/g dry
      matter; P = 0.025; n = 25) in the CaP period. Bile acid excretion increased
      during the CaP period compared with the placebo period (25.4 vs. 22.9 micromol/g
      dry matter; P = 0.003). The observed beneficial effects on cholesterol metabolism
      are not the result of an increased excretion of cholesterol, but might be
      explained by an increased bile acid excretion and a subsequent regeneration of
      bile acids from endogenous cholesterol in the liver.

PMID- 15987850
TI  - Children's experiences of food insecurity can assist in understanding its effect
      on their well-being.
AB  - An understanding of the experience of food insecurity by children is essential
      for better measurement and assessment of its effect on children's nutritional,
      physical, and mental health. Our qualitative study explored children's
      perceptions of household food insecurity to identify these perceptions and to use
      them to establish components of children's food insecurity experience. Children
      (n = 32; 11-16 y old) from after school programs and a middle school in low
      income areas participated in individual semistructured in-depth interviews.
      Children as young as 11 y could describe behaviors associated with food
      insecurity if they had experienced it directly or indirectly. Using the constant
      comparative method of qualitative data analysis, children's descriptions of
      behaviors associated with food insecurity were categorized into components of
      quantity of food, quality of food, psychological aspects, and social aspects
      described in the household food insecurity literature. Aspects of quantity
      included eating less than usual and eating more or eating fast when food was
      available. Aspects of quality included use of a few kinds of low-cost foods.
      Psychological aspects included worry/anxiety/sadness about the family food
      supply, feelings of having no choice in the foods eaten, shame/fear of being
      labeled as poor, and attempts to shield children. Social aspects of food
      insecurity centered on using social networks to acquire food or money and social
      exclusion. These results provide valuable information in understanding the effect
      of food insecurity on children's well-being especially relative to the social and
      emotional aspects of well-being.

PMID- 15987851
TI  - Lactation counseling increases exclusive breast-feeding rates in Ghana.
AB  - Exclusive breast-feeding (EBF) rates remain low despite numerous health benefits
      associated with this behavior. We conducted a randomized trial on the effect of
      lactation counseling on EBF, which controlled for the Hawthorne effect while also
      varying the timing of the intervention. Pregnant women attending prenatal clinics
      in Tema were randomly assigned to 1 of 2 intervention groups (IG) or to a control
      group (C), as follows: 1) EBF support given pre-, peri-, and postnatally (IG1; n
      = 43); 2) EBF support given only peri- and postnatally (IG2; n = 44); or 3)
      nonbreast-feeding health educational support (C; n = 49) that had an equal amount
      of contact with lactation counselors. Two educational sessions were provided
      prenatally, and 9 home follow-up visits were provided in the 6-mo postpartum
      period. Infant feeding data were collected monthly at the participant's home. The
      3 groups did not differ in sociodemographic characteristics. At 6 mo postpartum,
      90.0% in IG1 and 74.4% in IG2 had exclusively breast-fed during the previous
      month. By contrast, only 47.7% in C were doing so (P = 0.008). Similarly, the
      percentage of EBF during the 6 mo was significantly higher (P = 0.02) among IG1
      and IG2 (39.5%) than among C (19.6%). The 100% increase in EBF rates can be
      attributed to the lactation counseling provided. Additional prenatal EBF support
      may not be needed within a context of strong routine prenatal EBF education.

PMID- 15987852
TI  - Rye bread enhances the production and plasma concentration of butyrate but not
      the plasma concentrations of glucose and insulin in pigs.
AB  - The present investigation was undertaken to study the gastrointestinal and
      physiologic properties of diets based on soft and crisp wheat and rye breads
      similar in dietary fiber (DF; 230-235 g/kg dry matter) but with different
      proportions of the main DF polymers: in wheat, cellulose, and in rye,
      arabinoxylans (AX). The 2 diets provided all macronutrients; consequently, they
      had lower fat and sugar contents and a higher DF content than human mixed diets.
      The nutritional properties were studied in experiments in which pigs with
      cannulated ilea and catheterized portal veins and mesenteric arteries served as
      models for humans. The characteristics studied were degradation of nutrients,
      flow at the ileum, fecal output, absorption of nutrients deriving from the
      assimilation of cereal carbohydrates, and the insulin response. Apparent
      viscosity at the terminal small intestine, the ileal flow of water, flow and
      digestibility of noncarbohydrate constituents, but not of carbohydrates at the
      terminal ileum or the plasma concentrations of glucose and insulin, were higher
      when pigs consumed the rye compared with the wheat diet. The 2 diets provided
      approximately equal amounts of carbohydrates available for fermentation in the
      large intestine but because AX from the rye diet was more degradable than
      cellulose from the wheat diet, the quantitative degradation in the large
      intestine was more than twice as high when pigs consumed the former compared with
      the latter diet. The consequences included moister feces and significantly
      enhanced gut production and plasma concentrations of butyrate when pigs consumed
      the rye diet compared with the wheat diet.

PMID- 15987853
TI  - Differences in the intramolecular structure of structured oils do not affect
      pancreatic lipase activity in vitro or the absorption by rats of (n-3) fatty
      acids.
AB  - The fatty acid composition and intramolecular structure of dietary
      triacylglycerols (TAGs) influence their absorption. We compared the in vitro
      pancreatic lipase activity and the lymphatic transport in rats of fish oil and 2
      enzymatically interesterified oils containing 10:0 and (n-3) PUFAs of marine
      origin to investigate whether the positional distribution of fatty acids
      influenced the overall bioavailability of (n-3) PUFAs in the body. The structured
      oils had the (n-3) PUFA either mainly at the sn-1,3 position (LML, M = medium
      chain fatty acid, L = long-chain fatty acid) or mainly at the sn-2 position
      (MLM). Oils were administered to lymph-cannulated rats and lymph was collected
      for 24 h. The fatty acid composition as well as the lipid class distribution of
      lymph samples was determined. In vitro pancreatic lipase activity was greater
      when fish oil was the substrate than when the structured oils were the substrates
      (P < 0.001 at 40 min). This was consistent with a greater 8-h recovery of total
      fatty acids from fish oil compared with the 2 structured oils (P < 0.05). The
      absorption profiles of MLM and LML in rats and their in vitro rates of lipase
      activity did not differ. This indicates that the absorption rate is highly
      influenced by the lipase activity, which in turn is affected by the fatty acid
      composition and intramolecular structure. The lipid class distribution in lymph
      collected from the 3 groups of rats did not differ. In conclusion, the
      intramolecular structure did not affect the overall absorption of (n-3) PUFAs.

PMID- 15987854
TI  - Dietary S-methylmethionine, a component of foods, has choline-sparing activity in
      chickens.
AB  - Acid hydrolysis of dehulled soybean meal (SBM) and corn gluten meal (CGM)
      followed by chromatographic amino acid analysis (ninhydrin detection) revealed
      substantial quantities of S-methylmethionine (SMM) in both ingredients (1.65 g
      SMM/kg SBM; 0.5 g SMM/kg CGM). Young chicks were used to quantify the methionine-
      (Met) and choline-sparing bioactivity of crystalline L-SMM, relative to L-Met and
      choline chloride standards in 3 assays. A soy isolate basal diet was developed
      that could be made markedly deficient in Met, choline, or both. When singly
      deficient in choline or in both choline and Met, dietary SMM addition produced a
      significant (P < 0.01) growth response. In Assay 2, dietary SMM did not affect (P
      > 0.10) growth of chicks fed a Met-deficient, choline-adequate diet. A standard
      curve growth assay revealed choline bioactivity values (wt:wt) of 14.2 +/- 0.8
      and 25.9 +/- 5.1 g/100 g SMM based on weight gain and gain:food responses,
      respectively. A fourth assay, using standard-curve procedures, showed choline
      bioactivity values of 20.1 +/- 1.1 and 22.9 +/- 1.7 g/100 g SMM based on weight
      gain and gain:food responses, respectively. It is apparent that SMM in foods and
      feeds has methylation bioactivity, and this has implications for proper
      assessment of dietary Met and choline requirements as well as their
      bioavailability in foods and feeds.

PMID- 15987855
TI  - Tissue distribution of quercetin in rats and pigs.
AB  - Quercetin is a dietary polyphenolic compound with potentially beneficial effects
      on health. Claims that quercetin has biological effects are based mainly on in
      vitro studies with quercetin aglycone. However, quercetin is rapidly metabolized,
      and we have little knowledge of its availability to tissues. To assess the long
      term tissue distribution of quercetin, 2 groups of rats were given a 0.1 or 1%
      quercetin diet [approximately 50 or 500 mg/kg body weight (wt)] for 11 wk. In
      addition, a 3-d study was done with pigs fed a diet containing 500 mg
      quercetin/kg body wt. Tissue concentrations of quercetin and quercetin
      metabolites were analyzed with an optimized extraction method. Quercetin and
      quercetin metabolites were widely distributed in rat tissues, with the highest
      concentrations in lungs (3.98 and 15.3 nmol/g tissue for the 0.1 and 1% quercetin
      diet, respectively) and the lowest in brain, white fat, and spleen. In the short
      term pig study, liver (5.87 nmol/g tissue) and kidney (2.51 nmol/g tissue)
      contained high concentrations of quercetin and quercetin metabolites, whereas
      brain, heart, and spleen had low concentrations. These studies have for the first
      time identified target tissues of quercetin, which may help to understand its
      mechanisms of action in vivo.

PMID- 15987856
TI  - A novel galactooligosaccharide mixture increases the bifidobacterial population
      numbers in a continuous in vitro fermentation system and in the proximal colonic
      contents of pigs in vivo.
AB  - Prebiotics are nondigestible food ingredients that encourage proliferation of
      selected groups of the colonic microflora, thereby altering the composition
      toward a more beneficial community. In the present study, the prebiotic potential
      of a novel galactooligosaccharide (GOS) mixture, produced by the activity of
      galactosyltransferases from Bifidobacterium bifidum 41171 on lactose, was
      assessed in vitro and in a parallel continuous randomized pig trial. In situ
      fluorescent hybridization with 16S rRNA-targeted probes was used to investigate
      changes in total bacteria, bifidobacteria, lactobacilli, bacteroides, and
      Clostridium histolyticum group in response to supplementing the novel GOS
      mixture. In a 3-stage continuous culture system, the bifidobacterial numbers for
      the first 2 vessels, which represented the proximal and traverse colon, increased
      (P < 0.05) after the addition of the oligosaccharide mixture. In addition, the
      oligosaccharide mixture strongly inhibited the attachment of enterohepatic
      Escherichia coli (P < 0.01) and Salmonella enterica serotype Typhimurium (P <
      0.01) to HT29 cells. Addition of the novel mixture at 4% (wt:wt) to a commercial
      diet increased the density of bifidobacteria (P < 0.001) and the acetate
      concentration (P < 0.001), and decreased the pH (P < 0.001) compared with the
      control diet and the control diet supplemented with inulin, suggesting a great
      prebiotic potential for the novel oligosaccharide mixture.

PMID- 15987857
TI  - Magnesium proteinate is more protective than magnesium oxide in heat-stressed
      quail.
AB  - We evaluated the effects of dietary supplementation with Mg-oxide and Mg
      proteinate on performance; nutrient digestibilities; malondialdehyde (MDA)
      concentrations in serum, liver, and thigh meat; and serum cholesterol and
      triacylglycerol concentrations in Japanese quail (Coturnix coturnix japonica)
      exposed to high ambient temperature. The birds (n = 360; 10 d old) were randomly
      assigned to 12 treatment groups consisting of 6 replicates of 5 birds each in a 2
      x 2 x 3 factorial arrangement (temperature, Mg source, Mg level). Birds were
      maintained in temperature-controlled rooms at 22 degrees C for 24 h/d or 34
      degrees C for 8 h/d (0900-1700 h) and fed a basal diet or that diet supplemented
      with 1 or 2 g Mg-oxide or Mg-proteinate/kg of diet. Heat exposure decreased (P =
      0.0001) live weight gain, feed intake, feed efficiency, and carcass weight in
      quail fed the basal diet. A linear increase in feed intake (P = 0.008) and body
      weight (P = 0.001), and improvements in feed efficiency (P = 0.001), carcass
      weight (P < 0.0001), digestibility of dry matter, organic matter, crude protein,
      and ether extract were found in Mg-supplemented, heat-stressed quail. The effects
      of Mg-proteinate were greater than those of Mg-oxide (P < or = 0.0001). Serum Mg
      (P = 0.001) concentration increased, whereas the concentration of MDA in serum (P
      = 0.0001), liver (P = 0.04), and thigh meat (P = 0.0001) and serum triglyceride
      and cholesterol concentrations decreased linearly (P = 0.001) with the level of
      Mg in the diet. Interactions between dietary Mg source, temperature, and level of
      supplementation (P < or = 0.05) were found for several variables. Results of the
      present study suggest that supplementation with Mg-proteinate is more protective
      than Mg-oxide in reducing the negative effects of heat stress in quail.

PMID- 15987858
TI  - Dietary fat and an exogenous emulsifier increase the gastrointestinal absorption
      of a major soybean allergen, Gly m Bd 30K, in mice.
AB  - The mechanisms by which food allergens are absorbed and sensitized via the
      gastrointestinal tract have not been well characterized. In this study, the
      gastrointestinal absorption of a major soybean allergen, Gly m Bd 30K, in young
      and older mice, and the effects of dietary fat and exogenous emulsifier were
      investigated. In Expt. 1, Gly m Bd 30K [0, 500 or 2000 mg/kg body weight (BW)]
      was administered orally to 24-d-old mice, and blood was sampled at various time
      points over a 120-min period. Plasma Gly m Bd 30K was measured by sandwich ELISA
      and immunoblotting. Its concentration peaked at 30 min and was dose dependent.
      Intact Gly m Bd 30K and its 20-kDa fragments were identified in plasma after
      absorption. In Expt. 2, 24-d-old mice administered soy milk containing 1 mg Gly m
      Bd 30K showed a steady increase in plasma Gly m Bd 30K from 60 to 120 min that
      was significantly higher than that in 10-wk-old mice. In Expt. 3, when corn oil
      (5 or 30%) was coadministered with Gly m Bd 30K (2000 mg/kg BW) to 24-d-old mice,
      the plasma concentration increased significantly and generally reached a plateau
      after 30 min. The absorption after the coadministration of 30% corn oil and 3%
      sucrose fatty acid ester was higher than after the administration of 30% corn oil
      alone. Intact Gly m Bd 30K and its fragments that were < 20 kDa survived
      digestion and were absorbed into the blood. We propose that absorption was
      enhanced by fat carrier-mediated transport.

PMID- 15987859
TI  - Dietary (n-3) polyunsaturated fatty acids modulate murine Th1/Th2 balance toward
      the Th2 pole by suppression of Th1 development.
AB  - We showed that dietary long-chain (n-3) PUFAs present in fish oil (FO) affect
      CD4(+) T cell proliferation and cytokine production in C57BL/6 mice. To test the
      hypothesis that the anti-inflammatory effect of dietary (n-3) PUFAs could be due
      to the indirect suppression of T helper (Th)1 cells by cross-regulation of
      enhanced Th2 activation, mice were fed a wash-out control diet [5% corn oil (CO),
      (n-6) PUFA] for 1 wk, followed by the control diet or a fish oil diet [1% CO + 4%
      FO, (n-3) PUFA] for 2 wk. Splenic CD4+ T cells were cultured under both neutral
      and Th2 polarizing conditions for 2 d. Cells were reactivated and analyzed for
      interleukin-4 and interferon-gamma by intracellular cytokine staining. Dietary
      fish oil significantly increased the percentage of Th2 polarized cells and
      suppressed Th1 cell frequency under neutral conditions. However, under Th2
      polarizing conditions, although the suppression of Th1 cells was maintained in FO
      fed mice, no effect was observed in Th2 cells. Dietary fish oil increased the
      Th2/Th1 ratio in the presence of homologous mouse serum under both neutral (P =
      0.0009) and Th2 polarizing conditions (P = 0.0185). The FO diet did not
      significantly affect proliferation under Th2 polarizing conditions. Thus, the
      anti-inflammatory effects of FO may be explained in part by a shift in the
      Th1/Th2 balance, due to the direct suppression of Th1 development, and not by
      enhancement of the propensity of CD4+ T cells to be polarized toward a Th2
      phenotype, at least in vitro.

PMID- 15987860
TI  - Alive and dead Lactobacillus rhamnosus GG decrease tumor necrosis factor-alpha
      induced interleukin-8 production in Caco-2 cells.
AB  - Certain probiotic bacteria show anti-inflammatory activity after being heat
      killed, whereas others do not, suggesting that the gastrointestinal environment
      may alter the activity of probiotic bacteria. Occasionally, probiotics are
      provided when a patient is also being treated with oral antibiotics; this may
      have an effect on the probiotic activity. We hypothesized that Lactobacillus
      rhamnosus GG (LGG) are capable of downregulating tumor necrosis factor-alpha
      (TNFalpha)-induced interleukin (IL)-8 production under all 3 of these conditions,
      and that LGG act through the nuclear factor kappaB (NFkappaB)/inhibitor of kappaB
      (IkappaB) pathway. Caco-2 cells were treated with live or heat-killed LGG in
      doses ranging from 10(4) to 10(10) cfu/L, in the presence or absence of
      antibiotics and TNFalpha in the media. TNFalpha-induced production of IL-8 by
      Caco-2 cells was modulated by LGG under all 3 conditions. However, higher doses
      of live LGG without TNFalpha in the presence or absence of antibiotics in vitro
      induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the
      TNFalpha-induced IL-8 production (P < 0.01), but by itself did not increase IL-8
      production at higher doses as markedly as live LGG (P < 0.05). LGG reduced the
      TNFalpha-induced NFkappaB translocation to the nucleus and lessened the decrease
      in IkappaB in the cytoplasm (P < 0.05). LGG reduced TNFalpha-induced IL-8
      production by affecting the NFkappaB/IkappaB pathway in Caco-2 cells. High doses
      of live LGG markedly increased IL-8 production, but heat-killed LGG caused only a
      slight increase in IL-8. Thus, heat-killed LGG may effectively ameliorate
      inflammation with a lower potential than live LGG at high doses to cause
      inflammation.

PMID- 15987861
TI  - Major dietary patterns and risk of renal cell carcinoma in a prospective cohort
      of Swedish women.
AB  - Links between specific foods and the risk of renal cell carcinoma (RCC) are not
      well established. Dietary patterns may be a better predictor of RCC risk. Our aim
      was to identify and examine major dietary patterns and their relation to the risk
      of RCC in a large prospective cohort study of Swedish women. Complete dietary
      information was available from a FFQ from 46,572 women aged 40-76 y at baseline.
      We conducted factor analysis to identify dietary patterns. Cox proportional
      hazard models were used to estimate rate ratios (RRs) and 95% CIs. During a mean
      of 14.3 y of follow-up, we identified 93 cases of RCC. We observed 3 major
      dietary patterns in the cohort: Healthy (vegetables, tomato, fish, fruits,
      poultry, whole grains), Western (sweets, processed meat, refined grains,
      margarine/butter, high-fat dairy products, fried potato, soft drinks, meat) and
      Drinker (wine, hard liquor, beer, snacks) pattern. Higher Healthy pattern scores
      were not significantly associated with decreased risk of RCC (highest vs. lowest
      tertile RR = 0.81; 95% CI 0.45-1.48 and RR = 0.54; 95% CI 0.27-1.10 among women <
      or = 65 y). There was a suggestion of an inverse association between the Drinker
      pattern and RCC risk (RR comparing the 2nd and 3rd with the first tertile, 0.56;
      95% CI, 0.34-0.95; and 0.72; 95% CI, 0.42-1.22, respectively, P = 0.08 by Wald
      test); the association was clearer among women < or = 65 y (P = 0.02 by Wald
      test). Our data suggest an inverse association between Drinker pattern and the
      risk of RCC.

PMID- 15987862
TI  - Some dietary and adipose tissue carotenoids are associated with the risk of
      nonfatal acute myocardial infarction in Costa Rica.
AB  - Antioxidants, particularly carotenoids and tocopherols, may protect against
      cardiovascular disease. The objective of this study was to determine whether
      dietary and adipose tissue carotenoids and tocopherols are associated with the
      risk of myocardial infarction (MI). Cases (n = 1456) of a first acute MI were
      identified and matched by age, sex, and residence to randomly selected population
      controls (n = 1456) living in Costa Rica. Carotenoids and tocopherols were
      measured in adipose tissue using HPLC. Dietary intake was assessed using a
      validated FFQ. Anthropometrical and lifestyle data were collected using an
      interviewer-administered questionnaire. Subjects were distributed into quintiles
      of intake or adipose tissue concentration of carotenoids or tocopherols. The
      lowest quintile was used as the referent in conditional logistic regression
      analyses. Adipose tissue beta-carotene showed a significant inverse relation with
      MI risk; the odds ratio (OR) comparing the highest to the lowest quintile was
      0.70 (95% CI: 0.51-0.96, P for trend = 0.02). Intake of fruits and vegetables
      that are rich in beta-carotene was also inversely associated with the risk of MI
      (OR = 0.74; CI: 0.54-1.01, P for trend = 0.09). In contrast, lutein + zeaxanthin
      in adipose tissue (OR = 1.46; CI: 1.05-2.05, P for trend = 0.02) and diet (OR =
      1.18; CI: 0.88-1.57, P for trend = 0.02) was positively associated with MI risk.
      MI risk was not associated with any of the other carotenoids or tocopherols in
      the diet or adipose tissue. Thus, the inverse association between beta-carotene
      and MI risk suggests that beta-carotene protects against MI or it is a marker of
      some protective factor in foods containing beta-carotene. The mechanism
      underlying the positive association between lutein + zeaxanthin and the risk of
      MI warrants investigation.

PMID- 15987863
TI  - Decreased consumption of dried mature beans is positively associated with
      urbanization and nonfatal acute myocardial infarction.
AB  - Legumes may protect against myocardial infarction (MI). The objective of this
      study was to determine whether consumption of dried mature beans (referred to as
      beans), the main legume in Latin America, is associated with MI. The cases (n =
      2119) were survivors of a first acute MI and were matched by age, sex, and area
      of residence to randomly selected population controls (n = 2119) in Costa Rica.
      Dietary intake was assessed with a validated FFQ. Of the population, 69% consumed
      > or = 1 serving of beans/d (1 serving = one-third cup of cooked beans,
      approximately 86 g). Consumption of > or = 1 serving/d was significantly higher
      (P < 0.001) in rural (81%) than in urban (65%) areas. Individuals who never eat
      dried beans or whose consumption was < 1 time/mo were classified as nonconsumers.
      Compared with nonconsumers, intake of 1 serving of beans/d was inversely
      associated with MI in analyses adjusted for smoking, history of diabetes, history
      of hypertension, abdominal obesity, physical activity, income, intake of alcohol,
      total energy, saturated fat, trans fat, polyunsaturated fat, and cholesterol
      [odds ratio (OR) = 0.62; 95% CI: 0.45-0.88]. No further protection was observed
      with increased number of servings/d (OR = 0.73; 95% CI: 0.52-1.03 for > 1
      serving/d). In summary, we found that consumption of 1 serving of beans/d is
      associated with a 38% lower risk of MI. No additional protection was observed at
      intakes > 1 serving/d. These findings are timely given the trend toward increased
      obesity, cardiovascular disease, and a reduction in the intake of beans in Latin
      American countries.

PMID- 15987864
TI  - Multivitamin supplementation of HIV-positive women during pregnancy reduces
      hypertension.
AB  - Hypertension during pregnancy increases fetal growth retardation, preterm
      deliveries, and perinatal deaths, and yet its causes remain unclear. In HIV
      infected women, preterm birth additionally increases the risk of HIV transmission
      to the infant. Oxidative stress and endothelial cell dysfunction of the placenta
      have been implicated in the development of hypertension during pregnancy. Vitamin
      intake can reduce oxidative stress and improve endothelial function. We therefore
      evaluated the effect of multivitamin (20 mg thiamine, 20 mg riboflavin, 25 mg B
      6, 50 microg B-12, 500 mg C, 30 mg E, and 0.8 mg folic acid) and vitamin A
      supplements (30 mg beta-carotene plus 5000 IU preformed vitamin A) in relation to
      hypertension during pregnancy (systolic blood pressure > or = 140 mm Hg or
      diastolic blood pressure > or = 90 mm Hg at any time during pregnancy). In a
      double-blind, placebo-controlled, randomized, clinical trial, conducted among
      1078 HIV-positive pregnant Tanzanian women, those who received multivitamins were
      38% less likely to develop hypertension during pregnancy than those who did not
      [relative risk (RR) = 0.62, 95% CI 0.40-0.94, P = 0.03]. There was no overall
      effect of vitamin A on hypertension during pregnancy (RR = 1.00, 95% CI 0.66
      1.51, P = 0.98). Hypertension during pregnancy was more likely in women with high
      baseline systolic blood pressure (>120 vs. < or = 120 mm Hg) (RR = 6.02, 95%CI
      2.59-13.97, P < 0.001), and those with higher mid-upper arm circumference (RR =
      1.12, 95% CI 1.04-1.19, P = 0.002). Taking multivitamins containing vitamins B,
      C, and E during pregnancy may be an inexpensive and effective strategy to improve
      the health of the mother and baby.

PMID- 15987865
TI  - Supplement use is associated with health status and health-related behaviors in
      the 1946 British birth cohort.
AB  - Use of dietary supplements may be one of a number of health-related behaviors
      that cluster together. The current study investigated the underlying diet, health
      related characteristics, and behaviors of users and nonusers of dietary
      supplements in a longitudinal study of health. Participants (n = 1776) completed
      a 5-d food diary including information on dietary supplement use (vitamins,
      minerals, and nutraceuticals) at age 53 y. Sociodemographic information and data
      on smoking, alcohol, and physical activity were obtained along with
      anthropometric measurements, blood pressure, and a blood sample (nonfasting
      subjects). A significantly greater percentage of women reported supplement use
      compared with men (45.1 vs. 25.2%). Supplement use was associated with lower BMI,
      lower waist circumference, higher plasma folate and plasma vitamin B-12
      concentrations, nonsmoking, participation in physical activity, and nonmanual
      social class in women and with plasma folate concentrations and participation in
      physical activity in men. Nonsupplement users tended to be nonconsumers of
      breakfast cereals, fruit, fruit juice, yogurt, oily fish, and olive oil and had
      lower dietary intakes of potassium, magnesium, phosphorus, iron, and vitamin C
      even after adjustment for sociodemographic and behavioral factors. Overall,
      supplement users tended to differ from nonsupplement users on a range of health
      related behaviors and health status indicators, although there were fewer
      significant associations in men. Similarly, dietary supplements users tended to
      have underlying diets that, were healthier and those taking supplements may be
      the least likely to need them. These results support the notion of a clustering
      of healthy behaviors and cardiovascular risk factors, particularly for women.

PMID- 15987866
TI  - High resolution inductively coupled plasma mass spectrometry allows rapid
      assessment of iron absorption in infants and children.
AB  - Stable isotope absorption studies of iron have been limited by the high cost and
      limited availability of isotope ratio analysis using thermal ionization MS
      (TIMS). The development of high-resolution double focusing inductively coupled
      plasma MS (ICP-MS) may permit more cost-efficient sample analysis due to its high
      throughput, lower cost, easy sample pretreatment, and greater availability. Our
      objective was to develop an ICP-MS methodology for the measurement of iron
      isotope ratios using very small blood volumes. We developed a technique using
      multiple iron-nickel mixing standard solutions to adjust for nickel interference
      calibration. RBC samples from human subjects previously given 58Fe and 57Fe were
      analyzed for iron isotope ratios and compared with our current methodology
      (TIMS). Reproducibility of iron isotope ratios provided external relative SD <
      0.5 and 0.7% (1 SD) for 57Fe/54Fe and 58Fe/54Fe, respectively. Iron isotope
      ratios from ICP-MS analysis did not differ from those from TIMS based on
      statistical analyses, nor did the calculated iron absorption values. The mean and
      SD of iron absorption did not differ when measured by TIMS or ICP-MS. A 2-microL
      RBC sample was sufficient for ICP-MS iron isotope ratio analysis with an internal
      relative SD < 0.5% and analytical time < 5 min. This technique may assist groups
      in increasing their use of stable isotope methods to assess iron absorption in
      infants and children.

PMID- 15987867
TI  - Computer access to research on dietary supplements: a database of federally
      funded dietary supplement research.
AB  - Dietary supplement use is prevalent in the United States, but support for
      supplement research has been relatively modest and only recently emphasized at
      the NIH. The Dietary Supplement Health and Education Act of 1994 led to the
      creation of the Office of Dietary Supplements (ODS) at the NIH to promote
      research on dietary supplements. In order to track federally funded dietary
      supplement research, the ODS developed a database known as Computer Access to
      Research on Dietary Supplements (CARDS). This article provides an overview of the
      development and potential uses of the CARDS database. In addition, we report that
      NIH-funded dietary supplement research steadily increased from fiscal year (FY)
      1999 through 2002. The majority of NIH institutes or centers (ICs) funded
      research relevant to dietary supplements during this time, led by the National
      Cancer Institute and one of the newest NIH ICs, the National Center for
      Complementary and Alternative Medicine. CARDS data indicate that NIH-funded
      dietary supplement research from FY 1999 through 2002 involved primarily
      vitamins, minerals, botanicals and phytochemicals. Cancer and cardiovascular
      disease, two of the leading causes of morbidity and mortality in the United
      States, collectively accounted for almost 45% of the research related to dietary
      supplements. A variety of types of research studies were funded, with the
      majority consisting of human intervention studies. This information is useful to
      evaluate trends in federally funded dietary supplement research, identify
      research gaps, and help research scientists identify potential sources of NIH
      funding.

PMID- 15987868
TI  - Nutritional consequences of critical illness myopathies.

PMID- 15987869
TI  - Apoptosis of skeletal muscle on steroid-induced myopathy in rats.
AB  - Apoptotic cell death of differentiated skeletal muscle has been reported in an
      experimental steroid-induced myopathy of rats. To investigate the underlying
      molecular changes in the apoptosis of skeletal muscle, in situ end labeling
      (ISEL), Fas expression, and Western blot analysis for apoptosis-related proteins
      in the soleus muscle of triamcinolone acetonide (TA)-induced myopathy of rats
      were studied. Proteins for Western blot analysis included Fas-associated death
      domain (FADD) and caspase 8 for extrinsic pathway, as well as Bcl-2, Bcl-XL, Bax,
      Bad, Bid, Akt, p-Akt, and caspase 9 for intrinsic pathway. ISEL-positive
      myonuclei in TA-treated rats were 1.8 +/- 1.2%, whereas Fas-positive muscle
      fibers were 4.5 +/- 2.0%. One-fourth of Fas-positive muscle fibers had ISEL
      positive myonuclei. Levels of FADD, Bax, Bad, and Bid were substantially
      increased in the TA-induced myopathy group, whereas Bcl-2, Bcl-XL, Akt, p-Akt,
      and caspase 9 did not change between control and myopathy groups. Caspase 8
      activity increased in the myopathy group. These findings indicate that apoptosis
      of skeletal muscle in TA-induced myopathy may be triggered by Fas-Fas ligand
      signals and promoted mainly by overexpression of the pro-apoptotic molecules of
      FADD and caspase 8 involving the extrinsic pathway. The apoptotic process
      presented in this study supports a direct, nongenomic effect of a glucocorticoid
      on cellular membranes leading to cellular apoptosis rather than genomic effector
      mechanism of steroid hormone mediated by cytosolic steroid receptors.

PMID- 15987870
TI  - Amino acid supplementation for reversing bed rest and steroid myopathies.
AB  - Muscular inactivity is inherent in many circumstances, including convalescence
      from serious illness or injury, spaceflight, and the progression of aging.
      Inactivity in a healthy individual leads to a decrease in whole-body protein
      turnover composed primarily of a decrease in muscle protein synthesis. The
      decrease in muscle protein synthesis leads to a substantial loss of lean body
      mass. We have demonstrated that this loss of lean mass is greater when inactivity
      is accompanied by stress, specifically hypercortisolemia. During convalescence
      from trauma or injury, the anabolic stimulus provided by nutrient ingestion
      represents a primary means of ameliorating the loss of muscle protein. We have
      previously demonstrated that ingestion of essential amino acids (EAAs),
      formulated to mimic the proportion of EAAs in muscle, provides a potent anabolic
      stimulus for muscle protein. Recently, we demonstrated that EAA supplementation
      throughout 28 d of bed rest stimulated net muscle protein synthesis. The repeated
      stimulation translated to maintenance of lean body mass and an amelioration of
      functional decrement compared to a placebo treatment. We have also demonstrated
      that this EAA supplement stimulates net protein synthesis during acute
      hypercortisolemia and are currently testing the effects during prolonged
      inactivity. Although EAAs promote muscle anabolism during hypercortisolemia, it
      is unlikely that a nutritional intervention alone would be effective in
      maintaining lean body mass during severe stress. It may be necessary to
      concomitantly reduce the catabolic influence of cortisol or provide another
      anabolic stimulus.

PMID- 15987871
TI  - Understanding critical illness myopathy: approaching the pathomechanism.
AB  - Myopathies occurring in critically ill patients have gained increasing interest
      during the past years. For the patient, they represent a crucial factor for
      prolonged intensive care unit treatment and secondary complications. Critical
      illness myopathies (CIMs) seem to be related to various pathogenic factors. Among
      those, the septic inflammatory response syndrome seems to play a major role. It
      has been suggested that, similar to sepsis-related multiorgan failure, CIM might
      be considered a failure of the organ muscle. Muscle function might be impaired by
      proposed "myotoxic" humoral factors. These could be endogenously produced during
      the innate immune response to sepsis. This article follows up recent evidence for
      such active fractions in the blood serum of CIM patients. To explain muscle
      weakness in CIM, serum fractions acutely modified membrane excitability and
      subcellular Ca2+ regulation in an animal model. From the differential serum
      effects, early-phase CIM seems to involve a reduction in the overall force
      generation in muscle but also a compensation by the membrane, increasing the
      excitability. Different animal models will help to elucidate the underlying
      mechanisms accounting for the specific proteolytic activities found in different
      forms of CIM. CIM represents a systemic rather than a local disorder. Humoral
      factors might initiate the local reaction of skeletal muscle clinically seen as
      muscle weakness, altered excitability, and proteolysis of contractile proteins.
      Establishing the interactions in the excitation-contraction cascade in CIM is a
      challenging task, not only to clarify its pathomechanism but also to deduce
      clinical interventions.

PMID- 15987872
TI  - Myopathies in critical illness: characterization and nutritional aspects.
AB  - Myopathies related to critical illness have received increasing recognition over
      the past decade and are common in patients even after a brief period in the
      intensive care unit. Recent studies have revealed that myopathies in the
      critically ill may in fact be more prevalent than neuropathies and that morbidity
      and mortality may be greater. Protein catabolism, an increase in urinary nitrogen
      loss, and muscle wasting are observed in critical illness myopathy. Muscle
      biopsies in critically ill patients demonstrate low glutamine levels, low
      protein/DNA levels, and high concentrations of extracellular water. The increased
      flux of glutamine in muscle in these patients is thought to be insufficient to
      meet the body's requirement for glutamine, and thus in critical illness this
      amino acid may be classified as "conditionally essential." Three subtypes of
      critical illness myopathy have been described that are often grouped together as
      acute quadriplegic myopathy: thick-filament myopathy, critical illness myopathy,
      and necrotizing myopathy. These can be differentiated based on clinical features
      and muscle biopsy. Treatments for critical illness myopathies range from primary
      prevention, i.e., avoiding myopathy-inducing drugs, to novel nutritional
      therapies, such as glutamine and glutathione supplementation. One should be
      particularly vigilant for the development of myopathies in critically ill
      alcoholic patients, who may have a chronic alcoholic myopathy at baseline. In the
      past decade, advances have been made in characterizing and identifying patients
      with myopathies due to critical illness. However, additional studies must be
      performed in order to develop appropriate therapies for this potentially
      devastating disorder.

PMID- 15987873
TI  - Metabolic consequences of muscle disuse atrophy.
AB  - In response to decreased usage, skeletal muscle undergoes an adaptive reductive
      remodeling. This adaptive response has been found with disuse during human
      spaceflight, rat spaceflight, rat hind-limb unloading, bed rest, and aging. The
      reductive remodeling of skeletal muscle with disuse is largely independent of the
      reason for the disuse. The process involves more than a transition from slow to
      fast myosin fiber types. There are associated metabolic changes including a fuel
      shift toward glycolysis, decreased capacity for fat oxidation, and energy
      substrate accumulation in the atrophied muscles. Glycolysis is very effective for
      high-intensity short-duration acute activities, but if sustained output is
      needed, an energy profile where fat use is favored rather than compromised is
      desirable. For astronauts, there is a need to maintain as much functional
      capacity as possible during spaceflight for extravehicular activities. The shift
      toward increased activity of the glycolytic enzymes in atrophied muscle is
      accommodated by an increase in gluconeogenic capacity in the liver.

PMID- 15987874
TI  - Inferring the effects of demography and selection on Drosophila melanogaster
      populations from a chromosome-wide scan of DNA variation.
AB  - Identifying regions of the Drosophila melanogaster genome that have been recent
      targets of positive Darwinian selection will provide evidence for adaptations
      that have helped this species to colonize temperate habitats. We have begun a
      search for such genomic regions by analyzing multiple loci (about 250) dispersed
      across the X chromosome in a putatively ancestral population from East Africa and
      a derived European population. For both populations we found evidence for past
      changes in population size. We estimated that a major bottleneck associated with
      the colonization of Europe occurred about 3,500-16,000 years ago. We also found
      that while this bottleneck can account for most of the reduction in variation
      observed in the European sample, there is a deficit of polymorphism in some
      genomic regions that cannot be explained by demography alone.

PMID- 15987875
TI  - Gene expression evolves faster in narrowly than in broadly expressed mammalian
      genes.
AB  - Despite much recent interest, it remains unclear what determines the rate of
      evolution of gene expression. To study this issue we develop a new measure,
      called "Expression Conservation Index" (ECI), to quantify the degree of tissue
      expression conservation between two homologous genes. Applying this measure to a
      large set of gene expression data from human and mouse, we show that tissue
      expression tends to evolve rapidly for genes that are expressed in only a limited
      number of tissues, whereas tissue expression can be conserved for a long time for
      genes expressed in a large number of tissues. Therefore, expression breadth is an
      important determinant for evolutionary conservation of tissue expression. In
      addition, we find a rapid decrease in ECI with the synonymous divergence between
      duplicate genes, suggesting fast divergence in tissue expression between
      duplicate genes.

PMID- 15987876
TI  - Molecular mechanisms of extensive mitochondrial gene rearrangement in
      plethodontid salamanders.
AB  - Extensive gene rearrangement is reported in the mitochondrial genomes of lungless
      salamanders (Plethodontidae). In each genome with a novel gene order, there is
      evidence that the rearrangement was mediated by duplication of part of the
      mitochondrial genome, including the presence of both pseudogenes and additional,
      presumably functional, copies of duplicated genes. All rearrangement-mediating
      duplications include either the origin of light-strand replication and the nearby
      tRNA genes or the regions flanking the origin of heavy-strand replication. The
      latter regions comprise nad6, trnE, cob, trnT, an intergenic spacer between trnT
      and trnP and, in some genomes, trnP, the control region, trnF, rrnS, trnV, rrnL,
      trnL1, and nad1. In some cases, two copies of duplicated genes, presumptive
      regulatory regions, and/or sequences with no assignable function have been
      retained in the genome following the initial duplication; in other genomes, only
      one of the duplicated copies has been retained. Both tandem and nontandem
      duplications are present in these genomes, suggesting different duplication
      mechanisms. In some of these mitochondrial DNAs, up to 25% of the total length is
      composed of tandem duplications of noncoding sequence that includes putative
      regulatory regions and/or pseudogenes of tRNAs and protein-coding genes along
      with the otherwise unassignable sequences. These data indicate that imprecise
      initiation and termination of replication, slipped-strand mispairing, and
      intramolecular recombination may all have played a role in generating repeats
      during the evolutionary history of plethodontid mitochondrial genomes.

PMID- 15987877
TI  - Molecular evolutionary analyses of the odorant-binding protein gene Gp-9 in fire
      ants and other Solenopsis species.
AB  - The fire ant Solenopsis invicta exists in two social forms, one with colonies
      headed by a single reproductive queen (monogyne form) and the other with colonies
      containing multiple queens (polygyne form). This variation in social organization
      is associated with variation at the gene Gp-9, with monogyne colonies harboring
      only the B allelic variant and polygyne colonies containing b-like variants as
      well. We generated new Gp-9 sequences from 15 Solenopsis species and combined
      these with previously published sequences to conduct a comprehensive,
      phylogenetically based study of the molecular evolution of this important gene.
      The exon/intron structure and the respective lengths of the five exons of Gp-9
      are identical across all species examined, and we detected no evidence for
      intragenic recombination. These data conform to a previous suggestion that Gp-9
      lies in a genomic region with low recombination, and they indicate that evolution
      of the coding region in Solenopsis has involved point substitutions only. Our
      results confirm a link between the presence of b-like alleles and the expression
      of polygyny in all South American fire ant species known to possess colonies of
      both social forms. Moreover, phylogenetic analyses show that b-like alleles
      comprise a derived clade of Gp-9 sequences within the socially polymorphic
      species, lending further support to the hypothesis that monogyny preceded
      polygyny in this group of fire ants. Site-specific maximum likelihood tests
      identified several amino acids that have experienced positive selection, two of
      which are adjacent to the inferred binding-pocket residues in the GP-9 protein.
      Four other binding-pocket residues are variable among fire ant species, although
      selection is not implicated in this variation. Branch-specific tests revealed
      strong positive selection on the stem lineage of the b-like allele clade, as
      expected if selection drove the amino acid replacements crucial to the expression
      of polygyne social organization. Such selection may have operated via the ligand
      binding properties of GP-9, as one of the two amino acids uniquely shared by all
      b-like alleles is predicted to be a binding-pocket residue.

PMID- 15987878
TI  - MUSTANG is a novel family of domesticated transposase genes found in diverse
      angiosperms.
AB  - While transposons have traditionally been viewed as genomic parasites or "junk
      DNA," the discovery of transposon-derived host genes has fueled an ongoing debate
      over the evolutionary role of transposons. In particular, while mobility-related
      open reading frames have been known to acquire host functions, the contribution
      of these types of events to the evolution of genes is not well understood. Here
      we report that genome-wide searches for Mutator transposase-derived host genes in
      Arabidopsis thaliana (Columbia-0) and Oryza sativa ssp. japonica (cv. Nipponbare)
      (domesticated rice) identified 121 sequences, including the taxonomically
      conserved MUSTANG1. Syntenic MUSTANG1 orthologs in such varied plant species as
      rice, poplar, Arabidopsis, and Medicago truncatula appear to be under purifying
      selection. However, despite the evidence of this pathway of gene evolution,
      MUSTANG1 belongs to one of only two Mutator-like gene families with members in
      both monocotyledonous and dicotyledonous plants, suggesting that Mutator-like
      elements seldom evolve into taxonomically widespread host genes.

PMID- 15987879
TI  - Rapid evolution of genomic Acp complement in the melanogaster subgroup of
      Drosophila.
AB  - Unusual properties of molecular evolution in reproduction-related Drosophila
      genes, including atypically rapid rates of protein evolution, support the idea
      that natural selection plays an important role in divergence of reproductive
      function in Drosophila. We used subtractive hybridization to investigate another
      potential side of evolution of the male reproductive transcriptome. We carried
      out a screen for genes with much greater transcript abundance in Drosophila
      simulans reproductive tracts than in Drosophila melanogaster reproductive tracts.
      Such genes could be present in both species but diverged dramatically in
      transcript abundance or could be present in D. simulans but absent from D.
      melanogaster. Here we report data from melanogaster subgroup species for three
      previously unknown accessory gland protein genes (Acps) identified in this
      screen. We found multiple Acps that were present in some lineages yet absent from
      other closely related melanogaster subgroup lineages, representing several losses
      of genes. An Acp that may have been lost in D. melanogaster and Drosophila erecta
      is segregating a null allele in Drosophila yakuba, yet shows evidence of adaptive
      protein evolution in contrasts of polymorphism and divergence within and between
      D. yakuba and its close relative, Drosophila teissieri. These data suggest that
      turnover of Acps occurs rapidly in Drosophila, consistent with rapid evolution of
      seminal fluid function.

PMID- 15987880
TI  - Activation shift from medial to lateral temporal cortex associated with recency
      judgements following impoverished encoding.
AB  - Recency judgements can be performed on the basis of across-event relational
      information that directly provides temporal order among past events. Non
      relational item-based information internal to individual past events, such as
      information retrieved through familiarity, may also contribute to recency
      judgements. The present functional magnetic resonance imaging study examined
      neural substrates for item-based processing during recency judgements as an
      alternative to relational recency judgements. One half of word stimuli were
      encoded relationally prior to recency judgements, and the relational encoding of
      the other half was hampered such that the words were processed relatively in an
      item-based manner. Brain activity in the medial temporal lobe was observed during
      recency judgements for words studied with relational memory processing, whereas
      brain activity in the lateral temporal cortex was observed during recency
      judgements for words studied relatively in an item-based manner. It was revealed
      further that recognition of individual words per se, which can also be regarded
      as familiarity/recency judgements but is non-relational in nature, also activated
      the lateral temporal region. These results indicate multiple routes for recency
      judgements within the temporal lobe that are recruited depending on how past
      episodes are represented and retrieved for judgements of their temporal order.

PMID- 15987883
TI  - Integrated modeling of the major events in the MHC class I antigen processing
      pathway.
AB  - Rational design of epitope-driven vaccines is a key goal of immunoinformatics.
      Typically, candidate selection relies on the prediction of MHC-peptide binding
      only, as this is known to be the most selective step in the MHC class I antigen
      processing pathway. However, proteasomal cleavage and transport by the
      transporter associated with antigen processing (TAP) are essential steps in
      antigen processing as well. While prediction methods exist for the individual
      steps, no method has yet offered an integrated prediction of all three major
      processing events. Here we present WAPP, a method combining prediction of
      proteasomal cleavage, TAP transport, and MHC binding into a single prediction
      system. The proteasomal cleavage site prediction employs a new matrix-based
      method that is based on experimentally verified proteasomal cleavage sites.
      Support vector regression is used for predicting peptides transported by TAP. MHC
      binding is the last step in the antigen processing pathway and was predicted
      using a support vector machine method, SVMHC. The individual methods are combined
      in a filtering approach mimicking the natural processing pathway. WAPP thus
      predicts peptides that are cleaved by the proteasome at the C terminus,
      transported by TAP, and show significant affinity to MHC class I molecules. This
      results in a decrease in false positive rates compared to MHC binding prediction
      alone. Compared to prediction of MHC binding only, we report an increased overall
      accuracy and a lower rate of false positive predictions for the HLA-A*0201, HLA
      B*2705, HLA-A*01, and HLA-A*03 alleles using WAPP. The method is available online
      through our prediction server at http://www-bs.informatik.uni-tuebingen.de/WAPP

PMID- 15987884
TI  - The E. coli NusA carboxy-terminal domains are structurally similar and show
      specific RNAP- and lambdaN interaction.
AB  - The carboxy-terminal domain of the transcription factor Escherichia coli NusA,
      NusACTD, interacts with the protein N of bacteriophage lambda, lambdaN, and the
      carboxyl terminus of the E. coli RNA polymerase alpha subunit, alphaCTD. We
      solved the solution structure of the unbound NusACTD with high-resolution nuclear
      magnetic resonance (NMR). Additionally, we investigated the binding sites of
      lambdaN and alphaCTD on NusACTD using NMR titrations. The solution structure of
      NusACTD shows two structurally similar subdomains, NusA(353-416) and NusA(431
      490), matching approximately two homologous acidic sequence repeats. Further
      characterization of NusACTD with 15N NMR relaxation data suggests that the
      interdomain region is only weakly structured and that the subdomains are not
      interacting. Both subdomains adopt an (HhH)2 fold. These folds are normally
      involved in DNA-protein and protein-protein interactions. NMR titration
      experiments show clear differences of the interactions of these two domains with
      alphaCTD and lambdaN, in spite of their structural similarity.

PMID- 15987885
TI  - Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated
      channels.
AB  - Acid-sensing ion channels (ASIC) are proton-gated sodium channels that have been
      implicated in pain transduction associated with acidosis in inflamed or ischemic
      tissues. APETx2, a peptide toxin effector of ASIC3, has been purified from an
      extract of the sea anemone Anthopleura elegantissima. APETx2 is a 42-amino-acid
      peptide cross-linked by three disulfide bridges. Its three-dimensional structure,
      as determined by conventional two-dimensional 1H-NMR, consists of a compact
      disulfide-bonded core composed of a four-stranded beta-sheet. It belongs to the
      disulfide-rich all-beta structural family encompassing peptide toxins commonly
      found in animal venoms. The structural characteristics of APETx2 are compared
      with that of PcTx1, another effector of ASIC channels but specific to the ASIC1a
      subtype and to APETx1, a toxin structurally related to APETx2, which targets the
      HERG potassium channel. Structural comparisons, coupled with the analysis of the
      electrostatic characteristics of these various ion channel effectors, led us to
      suggest a putative channel interaction surface for APETx2, encompassing its N
      terminus together with the type I-beta turn connecting beta-strands III and IV.
      This basic surface (R31 and R17) is also rich in aromatic residues (Y16, F15,
      Y32, and F33). An additional region made of the type II'-beta turn connecting
      beta-strands I and II could also play a role in the specificity observed for
      these different ion effectors.

PMID- 15987887
TI  - Glucosylation of beta-lactoglobulin lowers the heat capacity change of unfolding;
      a unique way to affect protein thermodynamics.
AB  - Chemical glycosylation of proteins occurs in vivo spontaneously, especially under
      stress conditions, and has been linked in a number of cases to diseases related
      to protein denaturation and aggregation. It is the aim of this work to study the
      origin of the change in thermodynamic properties due to glucosylation of the
      folded beta-lactoglobulin A. Under mild conditions Maillard products can be
      formed by reaction of epsilon-amino groups of lysines with the reducing group of,
      in this case, glucose. The formed conjugates described here have an average
      degree of glycosylation of 82%. No impact of the glucosylation on the protein
      structure is detected, except that the Stokes radius was increased by
      approximately 3%. Although at ambient temperatures the change in Gibbs energy of
      unfolding is reduced by 20%, the denaturation temperature is increased by 5
      degrees C. Using a combination of circular dichroism, fluorescence, and
      calorimetric approaches, it is shown that the change in heat capacity upon
      denaturation is reduced by 60% due to the glucosylation. Since in the denatured
      state the Stokes radius of the protein is not significantly smaller for the
      glucosylated protein, it is suggested that the nonpolar residues associate to the
      covalently linked sugar moiety in the unfolded state, thereby preventing their
      solvent exposure. In this way coupling of small reducing sugar moieties to
      solvent exposed groups of proteins offers an efficient and unique tool to deal
      with protein stability issues, relevant not only in nature but also for
      technological applications.

PMID- 15987886
TI  - Protein-protein interactions as a tool for site-specific labeling of proteins.
AB  - Probing structures and dynamics within biomolecules using ensemble and single
      molecule fluorescence resonance energy transfer requires the conjugation of
      fluorophores to proteins in a site-specific and thermodynamically nonperturbative
      fashion. Using single-molecule fluorescence-aided molecular sorting and the
      chymotrypsin inhibitor 2-subtilisin BPN' complex as an example, we demonstrate
      that protein-protein interactions can be exploited to afford site-specific
      labeling of a recombinant double-cysteine variant of CI2 without the need for
      extensive and time-consuming chromatography. The use of protein-protein
      interactions for site-specific labeling of proteins is compatible with and
      complementary to existing chemistries for selective labeling of N-terminal
      cysteines, and could be extended to label multiple positions within a given
      polypeptide chain.

PMID- 15987888
TI  - Oligomerization of the fifth transmembrane domain from the adenosine A2A
      receptor.
AB  - The human adenosine A2A receptor (A(2A)R) belongs to one of the largest family of
      membrane proteins, the G-protein coupled receptors (GPCRs), characterized by
      seven transmembrane (TM) helices. Little is known about the determinants of their
      structures, folding, assembly, activation mechanisms, and oligomeric states.
      Previous studies in our group showed that peptides corresponding to all seven TM
      domains form stable helical structures in detergent micelles and lipid vesicles.
      However, the peptides behave differently; TM5 is the only peptide to have a ratio
      [theta]222/[theta]208 obtained by circular dichroism (CD) spectroscopy>1. This
      finding suggested to us that TM5 might self-associate. In the present study, we
      investigate the unique properties of the TM5 domain. We performed detailed
      analyses of TM5 peptide behavior in membrane-mimetic environments using CD
      spectroscopy, fluorescence spectroscopy and Forster resonance energy transfer,
      and gel electrophoresis. We find that TM5 peptide has the ability to self
      associate to form oligomeric structures in various hydrophobic milieus and that
      these oligomers are highly resistant to temperature and chemical denaturation. We
      also find that mutation of the full-length A(2A)R at position M193, which is
      located in the fifth TM domain, noticeably alters A(2A)R monomer: dimer ratio as
      observed on SDS-PAGE. Our results suggest that parallel association of TM5 dimers
      may play a role in the known adenosine A2A receptor dimerization. This study
      represents the first evidence of an individual GPCR transmembrane domain self
      association.

PMID- 15987889
TI  - Simultaneous optimization of enzyme activity and quaternary structure by directed
      evolution.
AB  - Natural evolution has produced efficient enzymes of enormous structural
      diversity. We imitated this natural process in the laboratory to augment the
      efficiency of an engineered chorismate mutase with low activity and an unusual
      hexameric topology. By applying two rounds of DNA shuffling and genetic
      selection, we obtained a 400-fold more efficient enzyme, containing three non
      active-site mutations. Detailed biophysical characterization of the evolved
      variant suggests that it exists predominantly as a trimer in solution, but is
      otherwise similarly stable as the parent hexamer. The dramatic structural and
      functional effects achieved by a small number of seemingly innocuous
      substitutions highlights the utility of directed evolution for modifying protein
      protein interactions to produce novel quaternary states with optimized
      activities.

PMID- 15987890
TI  - Solution structure of the ubiquitin-like domain of human DC-UbP from dendritic
      cells.
AB  - The previously identified dendritic cell-derived ubiquitin-like protein (DC-UbP)
      was implicated in cellular differentiation and apoptosis. Sequence alignment
      suggested that it contains a ubiquitin-like (UbL) domain in the C terminus. Here,
      we present the solution NMR structure and backbone dynamics of the UbL domain of
      DC-UbP. The overall structure of the domain is very similar to that of Ub despite
      low similarity (<30%) in amino-acid sequence. One distinct feature of the domain
      structure is its highly positively charged surface that is different from the
      corresponding surfaces of the well-known UbL modifiers, Ub, NEDD8, and SUMO-1.
      The key amino-acid residues responsible for guiding polyubiquitinated proteins to
      proteasome degradation in Ub are not conserved in the UbL domain. This implies
      that the UbL domain of DC-UbP may have its own specific interaction partners with
      other yet unknown cellular functions related to the Ub pathway.

PMID- 15987891
TI  - A scalable, GFP-based pipeline for membrane protein overexpression screening and
      purification.
AB  - We describe a generic, GFP-based pipeline for membrane protein overexpression and
      purification in Escherichia coli. We exemplify the use of the pipeline by the
      identification and characterization of E. coli YedZ, a new, membrane-integral
      flavocytochrome. The approach is scalable and suitable for high-throughput
      applications. The GFP-based pipeline will facilitate the characterization of the
      E. coli membrane proteome and serves as an important reference for the
      characterization of other membrane proteomes.

PMID- 15987892
TI  - Mutagenic analysis of the nucleation propensity of oxidized Alzheimer's beta
      amyloid peptide.
AB  - The formation of polypeptide aggregates represents a nucleated polymerization
      reaction in which an initial nucleation event (lag phase) is followed by the
      extension of newly formed nuclei into larger aggregates, including fibrils
      (growth phase). The efficiencies of these reactions relate to the lag time (lag
      phase) and to the rate of aggregation (growth phase), which can be determined
      from experimental aggregation curves. Here we present a mutagenic analysis in
      which we replace valine 18 of the Alzheimer's Abeta (1-40) peptide with 17
      different amino acids and determine its effect on the lag time, and therefore, on
      the propensity of nucleation. Comparison with various physico-chemical properties
      shows that nucleation is affected in a predictable manner depending on the beta
      sheet propensity and hydrophobicity of residue 18. In addition, we observe a
      direct proportionality between the lag time and the rate of aggregation. These
      data imply that the two reactions, nucleation and polymerization, are governed by
      very similar physicochemical principles and that they involve the formation of
      the same types of noncovalent interactions.

PMID- 15987893
TI  - Solution structure of thioredoxin h1 from Arabidopsis thaliana.
AB  - Present in virtually every species, thioredoxins catalyze disulfide/dithiol
      exchange with various substrate proteins. While the human genome contains a
      single thioredoxin gene, plant thioredoxins are a complex protein family. A total
      of 19 different thioredoxin genes in six subfamilies has emerged from analysis of
      the Arabidopsis thaliana genome. Some function specifically in mitochondrial and
      chloroplast redox signaling processes, but target substrates for a group of eight
      thioredoxin proteins comprising the h subfamily are largely uncharacterized. In
      the course of a structural genomics effort directed at the recently completed A.
      thaliana genome, we determined the structure of thioredoxin h1 (At3g51030.1) in
      the oxidized state. The structure, defined by 1637 NMR-derived distance and
      torsion angle constraints, displays the conserved thioredoxin fold, consisting of
      a five-stranded beta-sheet flanked by four helices. Redox-dependent chemical
      shift perturbations mapped primarily to the conserved WCGPC active-site sequence
      and other nearby residues, but distant regions of the C-terminal helix were also
      affected by reduction of the active-site disulfide. Comparisons of the oxidized
      A. thaliana thioredoxin h1 structure with an h-type thioredoxin from poplar in
      the reduced state revealed structural differences in the C-terminal helix but no
      major changes in the active site conformation.

PMID- 15987894
TI  - The effect of long-range interactions on the secondary structure formation of
      proteins.
AB  - The influence of long-range residue interactions on defining secondary structure
      in a protein has long been discussed and is often cited as the current limitation
      to accurate secondary structure prediction. There are several experimental
      examples where a local sequence alone is not sufficient to determine its
      secondary structure, but a comprehensive survey on a large data set has not yet
      been done. Interestingly, some earlier studies denied the negative effect of long
      range interactions on secondary structure prediction accuracy. Here, we have
      introduced the residue contact order (RCO), which directly indicates the
      separation of contacting residues in terms of the position in the sequence, and
      examined the relationship between the RCO and the prediction accuracy. A large
      data set of 2777 nonhomologous proteins was used in our analysis. Unlike previous
      studies, we do find that prediction accuracy drops as residues have contacts with
      more distant residues. Moreover, this negative correlation between the RCO and
      the prediction accuracy was found not only for beta-strands, but also for alpha
      helices. The prediction accuracy of beta-strands is lower if residues have a high
      RCO or a low RCO, which corresponds to the situation that a beta-sheet is formed
      by beta-strands from different chains in a protein complex. The reason why the
      current study draws the opposite conclusion from the previous studies is
      examined. The implication for protein folding is also discussed.

PMID- 15987895
TI  - Structure-function analysis of the alpha5 and the alpha13 helices of human
      glucokinase: description of two novel activating mutations.
AB  - It was recently described that the alpha5 and the alpha13 helices of human
      pancreatic glucokinase play a major role in the allosteric regulation of the
      enzyme. In order to understand the structural importance of these helices, we
      have performed site-directed mutagenesis to generate glucokinase derivatives with
      altered residues. We have analyzed the kinetic parameters of these mutated forms
      and compared them with wild-type and previously defined activating mutations in
      these helices (A456V and Y214C). We found two new activating mutations, A460R and
      Y215A, which increase the affinity of the enzyme for glucose. Our results suggest
      that substitutions in the alpha5 or the alpha13 helices that favor the closed,
      active conformation of the enzyme, either by improving the interaction with
      surrounding residues or by improving the flexibility of the region defined by
      these two helices, enhance the affinity of the enzyme for glucose, and therefore
      its performance as a glucose phosphorylating enzyme.

PMID- 15987896
TI  - Interaction of serine acetyltransferase with O-acetylserine sulfhydrylase active
      site: evidence from fluorescence spectroscopy.
AB  - Serine acetyltransferase is a key enzyme in the sulfur assimilation pathway of
      bacteria and plants, and is known to form a bienzyme complex with O-acetylserine
      sulfhydrylase, the last enzyme in the cysteine biosynthetic pathway. The
      biological function of the complex and the mechanism of reciprocal regulation of
      the constituent enzymes are still poorly understood. In this work the effect of
      complex formation on the O-acetylserine sulfhydrylase active site has been
      investigated exploiting the fluorescence properties of pyridoxal 5'-phosphate,
      which are sensitive to the cofactor microenvironment and to conformational
      changes within the protein matrix. The results indicate that both serine
      acetyltransferase and its C-terminal decapeptide bind to the alpha-carboxyl
      subsite of O-acetylserine sulfhydrylase, triggering a transition from an open to
      a closed conformation. This finding suggests that serine acetyltransferase can
      inhibit O-acetylserine sulfhydrylase catalytic activity with a double mechanism,
      the competition with O-acetylserine for binding to the enzyme active site and the
      stabilization of a closed conformation that is less accessible to the natural
      substrate.

PMID- 15987897
TI  - Precursor complex structure of pseudouridine synthase TruB suggests coupling of
      active site perturbations to an RNA-sequestering peripheral protein domain.
AB  - The pseudouridine synthase TruB is responsible for the universally conserved post
      transcriptional modification of residue 55 of elongator tRNAs. In addition to the
      active site, the "thumb", a peripheral domain unique to the TruB family of
      enzymes, makes extensive interactions with the substrate. To coordinate RNA
      binding and release with catalysis, the thumb may be able to sense progress of
      the reaction in the active site. To establish whether there is a structural
      correlate of communication between the active site and the RNA-sequestering
      thumb, we have solved the structure of a catalytically inactive point mutant of
      TruB in complex with a substrate RNA, and compared it to the previously
      determined structure of an active TruB bound to a reaction product. Superposition
      of the two structures shows that they are extremely similar, except in the active
      site and, intriguingly, in the relative position of the thumb. Because the two
      structures were solved using isomorphous crystals, and because the thumb is very
      well ordered in both structures, the displacement of the thumb we observe likely
      reflects preferential propagation of active site perturbations to this RNA
      binding domain. One of the interactions between the active site and the thumb
      involves an active site residue whose hydrogen-bonding status changes during the
      reaction. This may allow the peripheral RNA-binding domain to monitor progress of
      the pseudouridylation reaction.

PMID- 15987898
TI  - Crystal structure and substrate specificity of the beta-ketoacyl-acyl carrier
      protein synthase III (FabH) from Staphylococcus aureus.
AB  - beta-Ketoacyl-ACP synthase III (FabH), an essential enzyme for bacterial
      viability, catalyzes the initiation of fatty acid elongation by condensing
      malonyl-ACP with acetyl-CoA. We have determined the crystal structure of FabH
      from Staphylococcus aureus, a Gram-positive human pathogen, to 2 A resolution.
      Although the overall structure of S. aureus FabH is similar to that of
      Escherichia coli FabH, the primer binding pocket in S. aureus FabH is
      significantly larger than that present in E. coli FabH. The structural
      differences, which agree with kinetic parameters, provide explanation for the
      observed varying substrate specificity for E. coli and S. aureus FabH. The rank
      order of activity of S. aureus FabH with various acyl-CoA primers was as follows:
      isobutyryl- > hexanoyl- > butyryl- > isovaleryl- >> acetyl-CoA. The availability
      of crystal structure may aid in designing potent, selective inhibitors of S.
      aureus FabH.

PMID- 15987899
TI  - Not all J domains are created equal: implications for the specificity of Hsp40
      Hsp70 interactions.
AB  - Heat shock protein 40s (Hsp40s) and heat shock protein 70s (Hsp70s) form
      chaperone partnerships that are key components of cellular chaperone networks
      involved in facilitating the correct folding of a broad range of client proteins.
      While the Hsp40 family of proteins is highly diverse with multiple forms
      occurring in any particular cell or compartment, all its members are
      characterized by a J domain that directs their interaction with a partner Hsp70.
      Specific Hsp40-Hsp70 chaperone partnerships have been identified that are
      dedicated to the correct folding of distinct subsets of client proteins. The
      elucidation of the mechanism by which these specific Hsp40-Hsp70 partnerships are
      formed will greatly enhance our understanding of the way in which chaperone
      pathways are integrated into finely regulated protein folding networks. From in
      silico analyses, domain swapping and rational protein engineering experiments,
      evidence has accumulated that indicates that J domains contain key specificity
      determinants. This review will critically discuss the current understanding of
      the structural features of J domains that determine the specificity of
      interaction between Hsp40 proteins and their partner Hsp70s. We also propose a
      model in which the J domain is able to integrate specificity and chaperone
      activity.

PMID- 15987900
TI  - An NMR view of the unfolding process of rusticyanin: Structural elements that
      maintain the architecture of a beta-barrel metalloprotein.
AB  - The unfolding process of the blue copper protein rusticyanin (Rc) as well as its
      dynamic and D(2)O/H(2)O exchange properties in an incipient unfolded state have
      been studied by heteronuclear NMR spectroscopy. Titrations of apo, Cu(I), and
      Cu(II)Rc with guanidinium chloride (GdmCl) show that the copper ion stabilizes
      the folded species and remains bound in the completely unfolded state. The
      oxidized state of the copper ion is more efficient than the reduced form in this
      respect. The long loop of Rc (where the first ligand of the copper ion is
      located) is one of the most mobile domains of the protein. This region has no
      defined secondary structure elements and is prone to exchange its amide protons.
      In contrast, the last loop (including a short alpha-helix) and the last beta
      strand (where the other three ligands of the metal ion are located) form the most
      rigid domain of the protein. The results taken as a whole suggest that the first
      ligand detaches from the metal ion when the protein unfolds, while the other
      three ligands remain bound to it. The implications of these findings for the
      biological folding process of Rc are also discussed.

PMID- 15987901
TI  - Improved membrane protein topology prediction by domain assignments.
AB  - Topology predictions for integral membrane proteins can be substantially improved
      if parts of the protein can be constrained to a given in/out location relative to
      the membrane using experimental data or other information. Here, we have
      identified a set of 367 domains in the SMART database that, when found in soluble
      proteins, have compartment-specific localization of a kind relevant for membrane
      protein topology prediction. Using these domains as prediction constraints, we
      are able to provide high-quality topology models for 11% of the membrane proteins
      extracted from 38 eukaryotic genomes. Two-thirds of these proteins are single
      spanning, a group of proteins for which current topology prediction methods
      perform particularly poorly.

PMID- 15987902
TI  - Design of improved membrane protein production experiments: quantitation of the
      host response.
AB  - Eukaryotic membrane proteins cannot be produced in a reliable manner for
      structural analysis. Consequently, researchers still rely on trial-and-error
      approaches, which most often yield insufficient amounts. This means that membrane
      protein production is recognized by biologists as the primary bottleneck in
      contemporary structural genomics programs. Here, we describe a study to examine
      the reasons for successes and failures in recombinant membrane protein production
      in yeast, at the level of the host cell, by systematically quantifying cultures
      in high-performance bioreactors under tightly-defined growth regimes. Our data
      show that the most rapid growth conditions of those chosen are not the optimal
      production conditions. Furthermore, the growth phase at which the cells are
      harvested is critical: We show that it is crucial to grow cells under tightly
      controlled conditions and to harvest them prior to glucose exhaustion, just
      before the diauxic shift. The differences in membrane protein yields that we
      observe under different culture conditions are not reflected in corresponding
      changes in mRNA levels of FPS1, but rather can be related to the differential
      expression of genes involved in membrane protein secretion and yeast cellular
      physiology.

PMID- 15987903
TI  - Lessons from the design of a novel atomic potential for protein folding.
AB  - We investigate all-atom potentials of mean force for estimating free energies in
      protein folding and fold recognition. We search through the space potentials and
      design novel atomic potentials with a random mixing approximation and a contact
      correlated Gaussian approximation of decoy states. We show that the two derived
      potentials are highly correlated, supporting the use of the random energy model
      as an accurate statistical description of protein conformational states. The
      novel atomic potentials perform well in a Z-score and fold decoy recognition
      test. Furthermore, the designed atomic potential performs slightly and
      significantly better than atomic potentials derived under a quasi-chemical
      assumption. While accounting for connectivity correlations between atom types
      does not improve the performance of the designed potential, we show these
      correlations lead to ambiguities in the distribution of energetic contributions
      for atoms on the same residue. Within the confines of the model then, many
      potentials may exist which stabilize all native folds in subtly different ways.
      Comparison of different protein conformations under the various atomic potentials
      reveals both a remarkable degree of correspondence in the estimated free energies
      and a remarkable degree of correspondence in the identity of the contacts types
      that make the dominant contributions to the estimated free energies. This
      consistency may be interpreted as a sign that the design procedure is extracting
      physically meaningful quantities.

PMID- 15987904
TI  - Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase
      inhibitors, as potential antidiabetic drugs.
AB  - Acyl ureas were discovered as a novel class of inhibitors for glycogen
      phosphorylase, a molecular target to control hyperglycemia in type 2 diabetics.
      This series is exemplified by 6-{2,6-Dichloro- 4-[3-(2-chloro-benzoyl)-ureido]
      phenoxy}-hexanoic acid, which inhibits human liver glycogen phosphorylase a with
      an IC(50) of 2.0 microM. Here we analyze four crystal structures of acyl urea
      derivatives in complex with rabbit muscle glycogen phosphorylase b to elucidate
      the mechanism of inhibition of these inhibitors. The structures were determined
      and refined to 2.26 Angstroms resolution and demonstrate that the inhibitors bind
      at the allosteric activator site, where the physiological activator AMP binds.
      Acyl ureas induce conformational changes in the vicinity of the allosteric site.
      Our findings suggest that acyl ureas inhibit glycogen phosphorylase by direct
      inhibition of AMP binding and by indirect inhibition of substrate binding through
      stabilization of the T' state.

PMID- 15987905
TI  - Protein flexibility prediction by an all-atom mean-field statistical theory.
AB  - We extended a mean-field model to proteins with all atomic detail. The all-atom
      mean-field model was used to calculate the dynamic and thermodynamic properties
      of a three-helix bundle fragment of Staphylococcal protein A (Protein Data Bank
      [PDB] ID 1BDD) and alpha-spectrin SH3 domain protein (PDB ID 1SHG). We show that
      a model with all-atomic detail provides a significantly more accurate prediction
      of flexibility of residues in proteins than does a coarse-grained residue-level
      model. The accuracy of flexibility prediction is further confirmed by application
      of the method to 18 additional proteins with the largest size of 224 residues.

PMID- 15987906
TI  - Identifying Plasmodium falciparum merozoite surface antigen 3 (MSP3) protein
      peptides that bind specifically to erythrocytes and inhibit merozoite invasion.
AB  - Receptor-ligand interactions between synthetic peptides and normal human
      erythrocytes were studied to determine Plasmodium falciparum merozoite surface
      protein-3 (MSP-3) FC27 strain regions that specifically bind to membrane surface
      receptors on human erythrocytes. Three MSP-3 protein high activity binding
      peptides (HABPs) were identified; their binding to erythrocytes became saturable,
      had nanomolar affinity constants, and became sensitive on being treated with
      neuraminidase and trypsin but were resistant to chymotrypsin treatment. All of
      them specifically recognized 45-, 55-, and 72-kDa erythrocyte membrane proteins.
      They all presented alpha-helix structural elements. All HABPs inhibited in vitro
      P. falciparum merozoite invasion of erythrocytes by ~55%-85%, suggesting that MSP
      3 protein's role in the invasion process probably functions by using mechanisms
      similar to those described for other MSP family antigens.

PMID- 15987907
TI  - Boundaries and physical characterization of a new domain shared between mammalian
      53BP1 and yeast Rad9 checkpoint proteins.
AB  - Eukaryotic cells have evolved DNA damage checkpoints in response to genome
      damage. They delay the cell cycle and activate repair mechanisms. The kinases at
      the heart of these pathways and the accessory proteins, which localize to DNA
      lesions and regulate kinase activation, are conserved from yeast to mammals. For
      Saccharomyces cerevisiae Rad9, a key adaptor protein in DNA damage checkpoint
      pathways, no clear human ortholog has yet been described in mammals. Rad9,
      however, shares localized homology with both human BRCA1 and 53BP1 since they all
      contain tandem C-terminal BRCT (BRCA1 C-terminal) motifs. 53BP1 is also a key
      mediator in DNA damage signaling required for cell cycle arrest, which has just
      been reported to possess a tandem Tudor repeat upstream of the BRCT motifs. Here
      we show that the major globular domain upstream of yeast Rad9 BRCT domains is
      structurally extremely similar to the Tudor domains recently resolved for 53BP1
      and SMN. By expressing several fragments encompassing the Tudor-related motif and
      characterizing them using various physical methods, we isolated the independently
      folded unit for yeast Rad9. As in 53BP1, the domain corresponds to the SMN Tudor
      motif plus the contiguous HCA predicted structure region at the C terminus. These
      domains may help to further elucidate the structural and functional features of
      these two proteins and improve knowledge of the proteins involved in DNA damage.

PMID- 15987908
TI  - Rv0216, a conserved hypothetical protein from Mycobacterium tuberculosis that is
      essential for bacterial survival during infection, has a double hotdog fold.
AB  - The Mycobacterium tuberculosis genome contains about 4000 genes, of which
      approximately a third code for proteins of unknown function or are classified as
      conserved hypothetical proteins. We have determined the three-dimensional
      structure of one of these, the rv0216 gene product, which has been shown to be
      essential for M. tuberculosis growth in vivo. The structure exhibits the greatest
      similarity to bacterial and eukaryotic hydratases that catalyse the R-specific
      hydration of 2-enoyl coenzyme A. However, only part of the catalytic machinery is
      conserved in Rv0216 and it showed no activity for the substrate crotonyl-CoA. The
      structure of Rv0216 allows us to assign new functional annotations to a family of
      seven other M. tuberculosis proteins, a number if which are essential for
      bacterial survival during infection and growth.

PMID- 15987909
TI  - The crystal structure of TrxA(CACA): Insights into the formation of a [2Fe-2S]
      iron-sulfur cluster in an Escherichia coli thioredoxin mutant.
AB  - Escherichia coli thioredoxin is a small monomeric protein that reduces disulfide
      bonds in cytoplasmic proteins. Two cysteine residues present in a conserved CGPC
      motif are essential for this activity. Recently, we identified mutations of this
      motif that changed thioredoxin into a homodimer bridged by a [2Fe-2S] iron-sulfur
      cluster. When exported to the periplasm, these thioredoxin mutants could restore
      disulfide bond formation in strains lacking the entire periplasmic oxidative
      pathway. Essential for the assembly of the iron-sulfur was an additional cysteine
      that replaced the proline at position three of the CGPC motif. We solved the
      crystalline structure at 2.3 Angstroms for one of these variants, TrxA(CACA). The
      mutant protein crystallized as a dimer in which the iron-sulfur cluster is
      replaced by two intermolecular disulfide bonds. The catalytic site, which forms
      the dimer interface, crystallized in two different conformations. In one of them,
      the replacement of the CGPC motif by CACA has a dramatic effect on the structure
      and causes the unraveling of an extended alpha-helix. In both conformations, the
      second cysteine residue of the CACA motif is surface-exposed, which contrasts
      with wildtype thioredoxin where the second cysteine of the CXXC motif is buried.
      This exposure of a pair of vicinal cysteine residues apparently allows
      thioredoxin to acquire an iron-sulfur cofactor at its active site, and thus a new
      activity and mechanism of action.

PMID- 15987910
TI  - Mycobacterium tuberculosis serine/threonine kinases PknB, PknD, PknE, and PknF
      phosphorylate multiple FHA domains.
AB  - The physiologic roles and the substrates of the Mycobacterium tuberculosis (Mtb)
      serine/threonine kinases are largely unknown. Here, we report six novel
      interactions of PknB, PknD, PknE, and PknF with the Forkhead-Associated (FHA)
      domains of Rv0020c and the putative ABC transporter Rv1747. Purified PknB and
      PknF kinase domains phosphorylated multiple FHA-domain proteins in vitro.
      Although they remain to be verified in vivo, these reactions suggest a web of
      interactions between STPKs and FHA domains.

PMID- 15987912
TI  - Images in clinical medicine. Calcific arteriopathy.

PMID- 15987911
TI  - Characterization of peptide folding nuclei by hydrogen/deuterium exchange-mass
      spectrometry.
AB  - Covalently linked pairs of well-chosen peptides can be good model systems for
      protein folding studies because they can adopt stable secondary, side-chain, and
      tertiary structure under certain conditions. We demonstrate a method for
      characterizing the structure in such peptide pairs by hydrogen/deuterium exchange
      of individual amide groups analyzed by collision-induced dissociation tandem mass
      spectrometry, in concert with circular dichroism spectroscopy. We apply the
      method to two peptides (and their three possible pairs) from bovine pancreatic
      trypsin inhibitor to address specific hypotheses regarding the stabilization of
      local secondary structure by long-range interactions.

PMID- 15987913
TI  - Genetic justice.

PMID- 15987914
TI  - DNA as evidence--the technology of identification.

PMID- 15987915
TI  - Close calls with club drugs.

PMID- 15987916
TI  - Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B.
AB  - BACKGROUND: Treatment with adefovir dipivoxil for 48 weeks resulted in
      histologic, virologic, and biochemical improvement in patients with hepatitis B e
      antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of
      continued therapy as compared with cessation of therapy. METHODS: One hundred
      eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to
      receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks (ratio,
      2:1). After week 48, patients receiving adefovir dipivoxil were again randomly
      assigned either to receive an additional 48 weeks of the drug or to switch to
      placebo. Patients originally assigned to placebo were switched to adefovir
      dipivoxil. Patients treated with adefovir dipivoxil during weeks 49 through 96
      were subsequently offered continued therapy. The primary end points were changes
      in hepatitis B virus (HBV) DNA and alanine aminotransferase levels. RESULTS:
      Treatment with adefovir dipivoxil resulted in a median decrease in serum HBV DNA
      of 3.47 log copies per milliliter (on a base-10 scale) at 96 weeks and 3.63 log
      copies per milliliter at 144 weeks. HBV DNA levels were less than 1000 copies per
      milliliter in 71 percent of patients at week 96 and 79 percent at week 144. In
      the majority of patients who were switched from adefovir dipivoxil to placebo,
      the benefit of treatment was lost (median change in HBV DNA levels from baseline,
      -1.09 log copies per milliliter; only 8 percent of patients had levels below 1000
      copies per milliliter at week 96). Side effects during weeks 49 through 144 were
      similar to those during the initial 48 weeks. Resistance mutations rtN236T and
      rtA181V were identified in 5.9 percent of patients after 144 weeks. CONCLUSIONS:
      In patients with HBeAg-negative chronic hepatitis B, the benefits achieved from
      48 weeks of adefovir dipivoxil were lost when treatment was discontinued. In
      patients treated for 144 weeks, benefits were maintained, with infrequent
      emergence of viral resistance.

PMID- 15987917
TI  - Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic
      hepatitis B.
AB  - BACKGROUND: Current treatments for chronic hepatitis B are suboptimal. In the
      search for improved therapies, we compared the efficacy and safety of pegylated
      interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine,
      and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)-positive
      chronic hepatitis B. METHODS: A total of 814 patients with HBeAg-positive chronic
      hepatitis B received either peginterferon alfa-2a (180 microg once weekly) plus
      oral placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine
      alone. The majority of patients in the study were Asian (87 percent). Most
      patients were infected with hepatitis B virus (HBV) genotype B or C. Patients
      were treated for 48 weeks and followed for an additional 24 weeks. RESULTS: After
      24 weeks of follow-up, significantly more patients who received peginterferon
      alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who
      received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19
      percent [P<0.001] and 27 percent vs. 19 percent [P=0.02], respectively) or HBV
      DNA levels below 100,000 copies per milliliter (32 percent vs. 22 percent
      [P=0.01] and 34 percent vs. 22 percent [P=0.003], respectively). Sixteen patients
      receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface
      antigen (HBsAg) seroconversion, as compared with 0 in the group receiving
      lamivudine alone (P=0.001). The most common adverse events were those known to
      occur with therapies based on interferon alfa. Serious adverse events occurred in
      4 percent, 6 percent, and 2 percent of patients receiving peginterferon alfa-2a
      monotherapy, combination therapy, and lamivudine monotherapy, respectively. Two
      patients receiving lamivudine monotherapy had irreversible liver failure after
      the cessation of treatment--one underwent liver transplantation, and the other
      died. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B,
      peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of
      HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.

PMID- 15987918
TI  - Capecitabine as adjuvant treatment for stage III colon cancer.
AB  - BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard
      adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an
      established alternative to bolus fluorouracil plus leucovorin as first-line
      treatment for metastatic colorectal cancer. We evaluated capecitabine in the
      adjuvant setting. METHODS: We randomly assigned a total of 1987 patients with
      resected stage III colon cancer to receive either oral capecitabine (1004
      patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983
      patients) over a period of 24 weeks. The primary efficacy end point was at least
      equivalence in disease-free survival; the primary safety end point was the
      incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS:
      Disease-free survival in the capecitabine group was at least equivalent to that
      in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis,
      P<0.001 for the comparison of the upper limit of the hazard ratio with the
      noninferiority margin of 1.20). Capecitabine improved relapse-free survival
      (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and
      was associated with significantly fewer adverse events than fluorouracil plus
      leucovorin (P<0.001). CONCLUSIONS: Oral capecitabine is an effective alternative
      to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon
      cancer.

PMID- 15987919
TI  - Daclizumab to prevent rejection after cardiac transplantation.
AB  - BACKGROUND: Daclizumab, a humanized monoclonal antibody against the interleukin-2
      receptor, reduced the risk of rejection without increasing the risk of infection
      among renal-transplant recipients and, in a single-center trial, among cardiac
      transplant recipients. We conducted a multicenter, placebo-controlled, double
      blind study to confirm these results in cardiac-transplant patients. METHODS: We
      randomly assigned 434 recipients of a first cardiac transplant treated with
      standard immunosuppression (cyclosporine, mycophenolate mofetil, and
      corticosteroids) to receive five doses of daclizumab or placebo. The primary end
      point was a composite of moderate or severe cellular rejection, hemodynamically
      significant graft dysfunction, a second transplantation, or death or loss to
      follow-up within six months. RESULTS: By six months, 104 of 218 patients in the
      placebo group had reached the primary end point, as compared with 77 of the 216
      patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1
      percent absolute risk reduction and a 25 percent relative reduction. The rate of
      rejection was lower in the daclizumab group than in the placebo group (41.3
      percent vs. 25.5 percent). Among patients reaching the primary end point, the
      median time to the end point was almost three times as long in the daclizumab
      group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1
      year (96 vs. 26 days). More patients in the daclizumab group than in the placebo
      group died of infection (6 vs. 0) when they received concomitant cytolytic
      therapy. CONCLUSIONS: Daclizumab was efficacious as prophylaxis against acute
      cellular rejection after cardiac transplantation. Because of the excess risk of
      death, concurrent or anticipated use of cytolytic therapy with daclizumab should
      be avoided.

PMID- 15987920
TI  - Clinical practice. Lung cancer screening.

PMID- 15987922
TI  - Images in clinical medicine. The virtual apple core of a colonic carcinoma.

PMID- 15987921
TI  - Gamma-hydroxybutyric acid.

PMID- 15987923
TI  - Case records of the Massachusetts General Hospital. Case 20-2005. A 58-year-old
      man with locally advanced pancreatic cancer.

PMID- 15987924
TI  - The maze of treatments for hepatitis B.

PMID- 15987925
TI  - Adjuvant therapy for colon cancer--the pace quickens.

PMID- 15987926
TI  - Immunosuppression in cardiac transplantation.

PMID- 15987927
TI  - Aspirin in the prevention of cardiovascular disease in women.

PMID- 15987928
TI  - The ubiquilin 1 gene and Alzheimer's disease.

PMID- 15987929
TI  - Cardiac revascularization in specialty and general hospitals.

PMID- 15987930
TI  - Polycystic ovary syndrome.

PMID- 15987931
TI  - Hypothyroidism due to ethionamide.

PMID- 15987932
TI  - Gestational exposure to lovastatin followed by cardiac malformation misclassified
      as holoprosencephaly.

PMID- 15987933
TI  - NMDA receptor subunit-dependent [Ca2+] signaling in individual hippocampal
      dendritic spines.
AB  - Ca2+ influx through synaptic NMDA receptors (NMDA-Rs) triggers a variety of
      adaptive cellular processes. To probe NMDA-R-mediated [Ca2+] signaling, we used
      two-photon glutamate uncaging to stimulate NMDA-Rs on individual dendritic spines
      of CA1 pyramidal neurons in rat brain slices. We measured NMDA-R currents at the
      soma and NMDA-R-mediated [Ca2+] transients in stimulated spines (Delta[Ca2+]).
      Uncaging-evoked NMDA-R current amplitudes were independent of the size of the
      stimulated spine, implying that smaller spines contain higher densities of
      functional NMDA-Rs. The ratio of Delta[Ca2+] over NMDA-R current was highly
      variable (factor of 10) across spines, especially for small spines. These
      differences were not explained by heterogeneity in spine sizes or diffusional
      coupling between spines and their parent dendrites. In addition, we find that
      small spines have NMDA-R currents that are sensitive to NMDA-R NR2B subunit
      specific antagonists. With block of NR2B-containing receptors, the range of
      Delta[Ca2+]/NMDA-R current ratios and their average value were much reduced. Our
      data suggest that individual spines can regulate the subunit composition of their
      NMDA-Rs and the effective fractional Ca2+ current through these receptors.

PMID- 15987934
TI  - Gustatory neural responses in the medial orbitofrontal cortex of the old world
      monkey.
AB  - The primary taste cortex has widespread and occasionally dense projections to the
      orbitofrontal cortex (OFC) in the macaque. Nonetheless, electrophysiological
      studies have revealed that only 2-8% of the cells in the OFC are activated by
      taste stimuli on the tongue. We describe an area centered in Brodmann's area 13m
      of the medial OFC (mOFC) where taste neurons are more concentrated. It consists
      of a 12 mm2 core, where gustatory neurons constituted 20% of the population, and
      a 1 mm perimeter in which 8% of the cells responded to taste. Data were collected
      from three awake cynomolgus monkeys (Macaca fascicularis) prepared for chronic
      recording. Single neurons were isolated with epoxylite-coated tungsten
      microelectrodes and tested for responsiveness to 1.0 m glucose, 0.3 m NaCl, 0.03
      m HCl, and 0.001 m QHCl. These stimuli elicited responses that were 96%
      excitatory and ranged from 5.2 to 5.9 spikes/s. Cells were broadly tuned (H =
      0.79), similar to those in the anterior insula (H = 0.70), and decidedly unlike
      the narrowly tuned taste neurons in the caudolateral OFC (clOFC; H = 0.39).
      Whereas 82% of the taste cells in the clOFC respond to glucose, in the mOFC, HCl
      responsive (56%), glucose-responsive (50%), NaCl-responsive (43%), and QHCl
      responsive (40%) cells were almost evenly represented. The mOFC taste area
      appears to comprise a major gustatory relay that lies anatomically and
      functionally between the anterior insula and the clOFC.

PMID- 15987935
TI  - Interplay between Na+/Ca2+ exchangers and mitochondria in Ca2+ clearance at the
      calyx of Held.
AB  - The clearance of Ca2+ from nerve terminals is critical for determining the build
      up of residual Ca2+ after repetitive presynaptic activity. We found previously
      that K+-dependent Na+/Ca2+ exchangers (NCKXs) show polarized distributions in
      axon terminals of supraoptic magnocellular neurons and play a major role in Ca2+
      clearance. The role of NCKXs in presynaptic terminals, however, has not been
      studied. We investigated the contribution of NCKX in conjunction with other Ca2+
      clearance mechanisms at the calyx of Held by analyzing the decay of Ca2+
      transients evoked by depolarizing pulses. Inhibition of Na+/Ca2+ exchange by
      replacing external Na+ with Li+ decreased the Ca2+ decay rate by 68%. Selective
      inhibition of NCKX by replacing internal K+ with TEA+ (tetraethylammonium) or Li+
      decreased the Ca2+ decay rate by 42%, and the additional inhibition of the K+
      independent form of Na+/Ca2+ exchanger (NCX) by reducing external [Na+] caused an
      additional decrease by 26%. Inhibition of plasma membrane Ca2+-ATPase (PMCA)
      decreased the Ca2+ decay rate by 23%, whereas inhibition of SERCA (smooth
      endoplasmic reticulum Ca2+-ATPase) had no effect. The contribution of
      mitochondria was negligible for small Ca2+ transients but became apparent at
      [Ca2+]i > 2.5 microM, when Na+/Ca2+ exchange became saturated. Mitochondrial
      contribution was also observed when the duration of Ca2+ transients was prolonged
      by inhibiting Na+/Ca2+ exchangers or by increasing Ca2+ buffers. These results
      suggest that, in response to small Ca2+ transients (<2 microM), Ca2+ loads are
      cleared from the calyx of Held by NCKX (42%), NCX (26%), and PMCA (23%), and that
      mitochondria participate when the Ca2+ load is larger or prolonged.

PMID- 15987936
TI  - A subpopulation of neurons in the medial prefrontal cortex encodes emotional
      learning with burst and frequency codes through a dopamine D4 receptor-dependent
      basolateral amygdala input.
AB  - The basolateral nucleus of the amygdala (BLA) and medial prefrontal cortex (mPFC)
      are involved importantly in the processing and encoding of emotionally salient
      learned associations. Here, we examined the possible role of the mPFC in the
      acquisition and encoding of emotional associative learning at the behavioral and
      single-neuron level. A subpopulation of neurons in the mPFC that received
      monosynaptic and orthodromic inputs from the BLA demonstrated strong associative
      responding to odors paired previously with footshock by increasing spontaneous
      activity and bursting activity. This occurred specifically in response to
      postconditioning presentations of the footshock-paired odors but not to odors
      presented in the absence of footshock. In contrast, mPFC neurons that failed to
      respond to BLA stimulation showed no associative responding. Systemic or intra
      mPFC blockade of dopamine (DA) D4 receptors prevented this emotional associative
      learning in neurons of the mPFC and blocked the expression of olfactory
      conditioned fear. These results demonstrate that individual neurons in the mPFC
      that receive a functional input from the BLA actively encode emotional learning
      and that this process depends on DA D4 receptor stimulation in the mPFC.

PMID- 15987937
TI  - The primate thalamus is a key target for brain dopamine.
AB  - The thalamus relays information to the cerebral cortex from subcortical centers
      or other cortices; in addition, it projects to the striatum and amygdala. The
      thalamic relay function is subject to modulation, so the flow of information to
      the target regions may change depending on behavioral demands. Modulation of
      thalamic relay by dopamine is not currently acknowledged, perhaps because
      dopamine innervation is reportedly scant in the rodent thalamus. We show that
      dopaminergic axons profusely target the human and macaque monkey thalamus using
      immunolabeling with three markers of the dopaminergic phenotype (tyrosine
      hydroxylase, dopamine, and the dopamine transporter). The dopamine innervation is
      especially prominent in specific association, limbic, and motor thalamic nuclei,
      where the densities of dopaminergic axons are as high as or higher than in the
      cortical area with the densest dopamine innervation. We also identified the
      dopaminergic neurons projecting to the macaque thalamus using retrograde tract
      tracing combined with immunohistochemistry. The origin of thalamic dopamine is
      multiple, and thus more complex, than in any other dopaminergic system defined to
      date: dopaminergic neurons of the hypothalamus, periaqueductal gray matter,
      ventral mesencephalon, and the lateral parabrachial nucleus project bilaterally
      to the monkey thalamus. We propose a novel dopaminergic system that targets the
      primate thalamus and is independent from the previously defined nigrostriatal,
      mesocortical, and mesolimbic dopaminergic systems. Investigating this "thalamic
      dopaminergic system" should further our understanding of higher brain functions
      and conditions such as Parkinson's disease, schizophrenia, and drug addiction.

PMID- 15987938
TI  - Nicotinic acetylcholine receptors at glutamate synapses facilitate long-term
      depression or potentiation.
AB  - The hippocampus is a center for learning and memory that receives abundant
      cholinergic innervation and richly expresses nicotinic acetylcholine receptors
      (nAChRs). Nicotinic mechanisms acting on the hippocampus influence attention,
      learning, and memory. During Alzheimer's dementia, nAChRs and cholinergic
      innervation decline in the hippocampus. Using mouse hippocampal slices, we
      examined the potential diversity of nAChR influences at the Schaffer collateral
      synapse onto CA1 pyramidal neurons. When nAChR currents were elicited locally at
      those excitatory synapses, various outcomes were possible depending on the
      relationship between the nAChR-mediated excitation and mild electrical
      stimulation. When mild presynaptic stimulation coincided with or preceded nAChR
      induced action potentials by 1-5 s, then long-term potentiation was induced.
      However, if the nAChR-induced action potentials fell within 1 s before the
      electrical stimulation, then long-term depression resulted. Outside of these time
      frames, the mismatch of nAChR activity and stimulation led to short-term
      potentiation. The results indicate that nAChRs may have various influences over
      excitatory events in the hippocampus. Ongoing nAChR activity likely modulates the
      impact of glutamate transmission and alters the probabilities for various forms
      of synaptic plasticity. The fine network of cholinergic fibers running through
      the hippocampus forms synaptic contacts onto pyramidal cells, granule cells, and
      interneurons, ensuring continual modulatory influence by nicotinic mechanisms
      throughout the hippocampal complex. Disruption of events such as those described
      here may contribute to the deficits associated with the decline of nicotinic
      cholinergic functions during degenerative diseases such as Alzheimer's dementia.

PMID- 15987939
TI  - Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory
      receptor neuron apoptosis.
AB  - Olfactory receptor neurons (ORNs) undergo caspase-mediated retrograde apoptosis
      after target removal (bulbectomy), in which axonal caspase-9 and caspase-3
      activation leads to terminal apoptosis in ORN soma of the olfactory epithelium.
      Here, we show that caspase-8 can act as an initiator of ORN apoptosis after
      bulbectomy and also after synaptic instability is induced by NMDA-mediated
      excitotoxic death of ORN target neurons in the olfactory bulb. Caspase-8 and
      caspase-3 are sequentially activated within ORN presynaptic terminals, and
      caspase-8 complexes with dynactin p150Glued, (a retrograde motor protein) and is
      transported retrogradely, preceding axonal caspase-3 activation and apoptosis of
      ORN cell bodies. Focal in vivo inhibition of initiator caspase activation or
      microtubule-dependent transport (with Taxol) at the lesioned axon terminus
      results in a significant reduction in retrograde axonal caspase-8 and caspase-3
      activation and inhibition of retrograde ORN death. Caspase-8 activation and
      retrograde transport after NMDA lesion is similarly reduced in mice null for p75,
      the low-affinity nerve growth factor receptor. The retrograde apoptosis of ORNs
      thus involves a novel mechanism that used p75 in the local activation of caspase
      8. Once caspase-8 is maximally activated in the presynaptic terminal, it is
      transported retrogradely by the motor complex dynactin/dynein, a process that can
      be inhibited focally to inhibit ORN apoptosis after acute axonal lesion. These
      data have revealed a novel mechanism of retrograde apoptosis, in which caspase-8
      complexes directly with axonal dynactin p150Glued to reveal a differential
      vulnerability of subpopulations of ORNs to undergo apoptosis after axonal damage
      and the loss of olfactory bulb target neurons.

PMID- 15987940
TI  - Integrin-mediated dendrite branch maintenance requires Abelson (Abl) family
      kinases.
AB  - Dendrite arbor structure is a critical determinant of nervous system function
      that must be actively maintained throughout life, but the signaling pathways that
      regulate dendrite maintenance are essentially unknown. We report that the Abelson
      (Abl) and Abl-related gene (Arg) nonreceptor tyrosine kinases are required for
      maintenance of cortical dendrites in the mouse brain. arg-/- cortical dendrites
      initially develop normally and are indistinguishable from wild-type dendrites at
      postnatal day 21. Dendrite branches are not efficiently maintained in arg-/-
      neurons, leading to a reduction in dendrite arbor size by early adulthood. More
      severe dendrite loss is observed in abl-/-arg-/- neurons. Elevation of Arg kinase
      activity in primary cortical neurons promotes axon and dendrite branching.
      Activation of integrin receptors by adhesion to laminin-1 or Semaphorin 7A also
      promotes neurite branching in cortical neurons, but this response is absent in
      arg-/- neurons because of the reduced dynamic behavior of mutant neurite
      branches. These data suggest that integrin signaling through Abl and Arg support
      cortical dendrite branch maintenance by promoting dendrite branch dynamics in
      response to adhesive cues.

PMID- 15987941
TI  - Epac mediates a cAMP-to-PKC signaling in inflammatory pain: an isolectin B4(+)
      neuron-specific mechanism.
AB  - The epsilon isoform of protein kinase C (PKCepsilon) has emerged as a critical
      second messenger in sensitization toward mechanical stimulation in models of
      neuropathic (diabetes, alcoholism, and cancer therapy) as well as acute and
      chronic inflammatory pain. Signaling pathways leading to activation of PKCepsilon
      remain unknown. Recent results indicate signaling from cAMP to PKC. A mechanism
      connecting cAMP and PKC, two ubiquitous, commonly considered separate pathways,
      remains elusive. We found that, in cultured DRG neurons, signaling from cAMP to
      PKCepsilon is not mediated by PKA but by the recently identified cAMP-activated
      guanine exchange factor Epac. Epac, in turn, was upstream of phospholipase C
      (PLC) and PLD, both of which were necessary for translocation and activation of
      PKCepsilon. This signaling pathway was specific to isolectin B4-positive [IB4(+)]
      nociceptors. Also, in a behavioral model, cAMP produced mechanical hyperalgesia
      (tenderness) through Epac, PLC/PLD, and PKCepsilon. By delineating this signaling
      pathway, we provide a mechanism for cAMP-to-PKC signaling, give proof of
      principle that the mitogen-activated protein kinase pathway-activating protein
      Epac also stimulates PKC, describe the first physiological function unique for
      the IB4(+) subpopulation of sensory neurons, and find proof of principle that G
      protein-coupled receptors can activate PKC not only through the G-proteins
      alpha(q) and betagamma but also through alpha(s).

PMID- 15987942
TI  - Reelin, very-low-density lipoprotein receptor, and apolipoprotein E receptor 2
      control somatic NMDA receptor composition during hippocampal maturation in vitro.
AB  - Reelin is a secreted protein that regulates brain layer formation during
      embryonic development. Reelin binds several receptors, including two members of
      the low-density lipoprotein (LDL) receptor family, the apolipoprotein E receptor
      2 (ApoER2) and the very-low-density lipoprotein receptor (VLDLR). Despite the
      high level of expression of Reelin and ApoER2 in the postnatal brain, their
      functions in the adult CNS remain elusive. Here, using electrophysiological,
      immunocytochemical, and biochemical approaches in cultured postnatal hippocampal
      neurons, we show that Reelin controls the change in subunit composition of
      somatic NMDA glutamate receptors (NMDARs) during maturation. We found that
      maturation is characterized by the gradual decrease of the participation of
      NR1/2B receptors to whole-cell NMDAR-mediated currents. This maturational change
      was mirrored by a timely correlated increase of both Reelin immunoreactivity in
      neuronal somata and the amount of secreted Reelin. Chronic blockade of the
      function of Reelin with antisense oligonucleotides or the function-blocking
      antibody CR-50 prevented the decrease of NR1/2B-mediated whole-cell currents.
      Conversely, exogenously added recombinant Reelin accelerated the maturational
      changes in NMDA-evoked currents. The maturation-induced change in NMDAR subunits
      also was blocked by chronic treatment with an inhibitor of the Src kinase
      signaling pathway or an antagonist of the LDL receptors, but not by inhibitors of
      another class of Reelin receptor belonging to the integrin family. Consistent
      with these results, immunocytochemistry revealed that NR1-expressing neurons also
      expressed ApoER2 and VLDLR. These data reveal a new role for Reelin and LDL
      receptors and reinforce the idea of a prominent role of extracellular matrix
      proteins in postnatal maturation.

PMID- 15987943
TI  - Effect of the temporal pattern of contralateral inhibition on sound localization
      cues.
AB  - We studied the temporal coding properties of identified interneurons in the
      auditory system of crickets, using information theory as an analytical tool. The
      ascending neuron 1 (AN1), which is tuned to the dominant carrier frequency (CF)
      of cricket songs, selectively codes the limited range of amplitude modulation
      (AM) frequencies that occur in these signals. AN2, which is most sensitive to the
      ultrasonic frequencies that occur in echolocation calls of insectivorous bats,
      codes a broader range of AM frequencies, as occur in bat calls. A third neuron,
      omega neuron 1 (ON1), which is dually tuned to both ranges of carrier frequency,
      was shown previously to have CF-specific coding properties, allowing it to
      represent accurately the differing temporal structures of both cricket songs and
      bat calls. ON1 is a source of contralateral inhibition to AN1 and AN2, enhancing
      binaural contrast and facilitating sound localization. We used dichotic
      stimulation to examine the importance of the temporal structure of contralateral
      inhibition for enhancing binaural contrast. Contralateral inhibition degrades the
      coding of temporal pattern by AN1 and AN2, but only if the temporal pattern of
      inhibitory input matches that of excitation. Firing rate is also decreased most
      strongly by temporally matched contralateral inhibition. This is apparent for AN1
      in its mean firing rate; for AN2, high-frequency firing is selectively
      suppressed. Our results show that the CF-specific coding properties of ON1 allow
      this single neuron to enhance effectively localization cues for both cricket-like
      and bat-like acoustic signals.

PMID- 15987944
TI  - Rapid, nongenomic responses to ecdysteroids and catecholamines mediated by a
      novel Drosophila G-protein-coupled receptor.
AB  - Nongenomic response pathways mediate many of the rapid actions of steroid
      hormones, but the mechanisms underlying such responses remain controversial. In
      some cases, cell-surface expression of classical nuclear steroid receptors has
      been suggested to mediate these effects, but, in a few instances, specific G
      protein-coupled receptors (GPCRs) have been reported to be responsible. Here, we
      describe the activation of a novel, neuronally expressed Drosophila GPCR by the
      insect ecdysteroids ecdysone (E) and 20-hydroxyecdysone (20E). This is the first
      report of an identified insect GPCR interacting with steroids. The Drosophila
      melanogaster dopamine/ecdysteroid receptor (DmDopEcR) shows sequence homology
      with vertebrate beta-adrenergic receptors and is activated by dopamine (DA) to
      increase cAMP levels and to activate the phosphoinositide 3-kinase pathway.
      Conversely, E and 20E show high affinity for the receptor in binding studies and
      can inhibit the effects of DA, as well as coupling the receptor to a rapid
      activation of the mitogen-activated protein kinase pathway. The receptor may thus
      represent the Drosophila homolog of the vertebrate "gamma-adrenergic receptors,"
      which are responsible for the modulation of various activities in brain, blood
      vessels, and pancreas. Thus, DmDopEcR can function as a cell-surface GPCR that
      may be responsible for some of the rapid, nongenomic actions of ecdysteroids,
      during both development and signaling in the mature adult nervous system.

PMID- 15987946
TI  - Reward-spatial view representations and learning in the primate hippocampus.
AB  - The primate anterior hippocampus (which corresponds to the rodent ventral
      hippocampus) receives inputs from brain regions involved in reward processing,
      such as the amygdala and orbitofrontal cortex. To investigate how this affective
      input may be incorporated into primate hippocampal function, we recorded neuronal
      activity while rhesus macaques performed a reward-place association task in which
      each spatial scene shown on a video monitor had one location that, if touched,
      yielded a preferred fruit juice reward and a second location that yielded a less
      preferred juice reward. Each scene had different locations for the different
      rewards. Of 312 neurons analyzed in the hippocampus, 18% responded more to the
      location of the preferred reward in different scenes, and 5% responded to the
      location of the less-preferred reward. When the locations of the preferred
      rewards in the scenes were reversed, 60% of 44 hippocampal neurons tested
      reversed the location to which they responded, showing that the reward-place
      associations could be altered by new learning in a few trials. The majority (82%)
      of these 44 hippocampal neurons tested did not respond to reward associations in
      a visual discrimination, object-reward association task. Thus, the primate
      hippocampus contains a representation of the reward associations of places "out
      there" being viewed. By associating places with the rewards available, the
      concept that the primate hippocampus is involved in object-place event memory is
      now extended to remembering goals available at different spatial locations. This
      is an important type of association memory.

PMID- 15987945
TI  - Sortilin controls intracellular sorting of brain-derived neurotrophic factor to
      the regulated secretory pathway.
AB  - Brain-derived neurotrophic factor (BDNF), after activity-dependent secretion from
      neurons, modulates critical nervous system functions. Recently, a variant in the
      human bdnf gene, resulting in a valine to methionine substitution in the
      prodomain, has been shown to lead to defective regulated secretion from neurons
      and memory impairment. Here, we report a novel function for a Vps10p domain
      protein, sortilin, in controlling BDNF sorting to the regulated secretory
      pathway. Sortilin interacts specifically with BDNF in a region encompassing the
      methionine substitution and colocalizes with BDNF in secretory granules in
      neurons. A truncated form of sortilin causes BDNF missorting to the constitutive
      secretory pathway without affecting neurotrophin-4 (NT-4) secretion. In addition,
      sortilin small interfering RNA introduced into primary neurons also led to BDNF
      missorting from the regulated to the constitutive secretory pathway. Together,
      these data suggest a mechanism to understand the defect associated with variant
      BDNF and provide a framework, based on divergent presynaptic regulation of
      sorting to secretory pathways, to explain how two ligands for tropomyosin-related
      kinase B, BDNF and NT-4, can mediate diverse biological responses.

PMID- 15987948
TI  - GABAergic inhibition controls neural gain in inferior colliculus neurons
      sensitive to interaural time differences.
AB  - We investigated the role of GABAergic inhibition on the responses of inferior
      colliculus (IC) neurons sensitive to interaural time differences (ITDs) in
      anesthetized guinea pigs. Responses to static and dynamic ITDs were obtained
      before, during, and after recovery from ionotophoretic application of GABA, or
      antagonists to the GABA(A) receptor gabazine and bicuculline. For most neurons, a
      linear relationship was observed between discharge rates evoked by a particular
      ITD during drug application and control discharge rates. Blocking GABAergic
      inhibition, or adding exogenous GABA, scaled IC discharge rates in a
      multiplicative (divisive) and/or additive (subtractive) manner. When the
      influence of iontophoresed GABA antagonists or exogenous GABA on discharge rates
      was accounted for, GABAergic inhibition was found to have no effect on the ITD
      tuning properties of IC neurons. The tuning sharpness of ITD functions, the ITD
      that evoked 50% response magnitude, and the relative symmetry of ITD functions
      around their peak response were unaffected by blockade of inhibition or addition
      of tonic inhibition. However, the ability of neurons to discriminate between ITDs
      by virtue of differences in their discharge rate was altered by blocking or
      adding GABA. We propose that inhibition in the IC is involved in the control of
      the neural gain of the output of IC neurons rather than the regulation of ITD
      tuning. This gain control appears to arise from a combination of additive and
      multiplicative processes, and may involve mechanisms such as shunting inhibition
      or changes in the efficacy of inhibitory and excitatory inputs.

PMID- 15987947
TI  - Bistable network behavior of layer I interneurons in auditory cortex.
AB  - GABAergic interneurons in many areas of the neocortex are mutually connected via
      chemical and electrical synapses. Previous computational studies have explored
      how these coupling parameters influence the firing patterns of interneuronal
      networks. These models have predicted that the stable states of such
      interneuronal networks will be either synchrony (near zero phase lag) or
      antisynchrony (phase lag near one-half of the interspike interval), depending on
      network connectivity and firing rates. In certain parameter regimens, the network
      can be bistable, settling into either stable state depending on the initial
      conditions. Here, we investigated how connectivity parameters influence spike
      patterns in paired recordings from layer I interneurons in brain slices from
      juvenile mice. Observed properties of chemical and electrical synapses were used
      to simulate connections between uncoupled cells via dynamic clamp. In uncoupled
      pairs, action potentials induced by constant depolarizing currents had randomly
      distributed phase differences between the two cells. When coupled with simulated
      chemical (inhibitory) synapses, however, these pairs exhibited a bimodal firing
      pattern, tending to fire either in synchrony or in antisynchrony. Combining
      electrical with chemical synapses, prolonging tau(Decay) of inhibitory
      connections, or increasing the firing rate of the network all resulted in
      enhanced stability of the synchronous state. Thus, electrical and inhibitory
      synaptic coupling constrain the relative timing of spikes in a two-cell network
      to, at most, two stable states, the stability and precision of which depend on
      the exact parameters of coupling.

PMID- 15987949
TI  - Retrograde endocannabinoid signaling in a postsynaptic neuron/synaptic bouton
      preparation from basolateral amygdala.
AB  - Retrograde synaptic signaling by endogenous cannabinoids (endocannabinoids) is a
      recently discovered form of neuromodulation in the brain. In the basolateral
      amygdala (BLA), endocannabinoid signaling has been implicated in learning and
      memory, specifically in extinction of aversive memories. To examine retrograde
      endocannabinoid signaling in this brain region, BLA neurons were freshly isolated
      using an enzyme-free procedure. These isolated neurons retain attached functional
      excitatory and inhibitory synaptic boutons. Spontaneous GABAergic IPSCs (sIPSCs)
      were isolated from these freshly isolated neurons and a 4 s step of
      depolarization from -60 to 0 mV produced suppression of sIPSC frequency and
      amplitude. A similar depolarization-induced suppression of inhibition (DSI) was
      observed in neurons in BLA slices. DSI in the single-cell preparation was
      abolished by the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1
      (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, and DSI duration was
      shortened in the presence of 2-methyl-6-(phenylethynyl) pyridine, an mGluR5
      (metabotropic glutamate receptor 5) antagonist. The initial decrease in sIPSCs
      induced by the DSI procedure was greatly attenuated in recordings with 20 mm
      BAPTA containing postsynaptic internal solution, but a delayed-onset decrease was
      observed under this recording condition. A CB1 agonist decreased sIPSC frequency
      and amplitude, whereas CB1 antagonists increased these responses. The antagonist
      induced increase was abolished in 20 mm BAPTA-filled cells. These data provide
      solid evidence for retrograde endocannabinoid signaling in the BLA and also
      indicate that this retrograde signaling requires only a postsynaptic neuron and
      attached synaptic boutons.

PMID- 15987950
TI  - Conditioned nicotine withdrawal profoundly decreases the activity of brain reward
      systems.
AB  - Withdrawal from nicotine decreases the activity of brain reward systems, measured
      in rats by elevations of intracranial self-stimulation (ICSS) thresholds. This
      reward deficit is hypothesized to contribute to the persistence of the tobacco
      habit in tobacco smokers. Accumulating evidence suggests that aspects of drug
      withdrawal may become conditioned to previously neutral environmental stimuli via
      pavlovian conditioning processes. Here we investigated whether hedonically
      neutral stimuli repeatedly paired with nicotine withdrawal gained "affective
      valence" such that withdrawal-associated conditioned stimuli alone decreased
      brain reward function. Nicotine-dependent rats were presented with a light/tone
      conditioned stimulus and injected with the nicotinic receptor antagonist dihydro
      beta-erythroidine (DHbetaE; 3 mg/kg) for 4 d consecutively; ICSS thresholds were
      assessed before and immediately after DHbetaE injection. On the test day, the
      rats were presented with the conditioned stimulus and injected with saline; next,
      ICSS thresholds were assessed. During conditioning sessions, DHbetaE elevated
      reward thresholds, and the magnitude by which thresholds were elevated increased
      during successive conditioning sessions. These data suggest that withdrawal
      associated conditioned stimuli potentiated the magnitude of nicotine withdrawal
      as their motivational significance increased. Most importantly, on the test day,
      the conditioned stimulus alone elevated reward thresholds. Similarly, in a
      separate experiment, withdrawal-associated cues elevated reward thresholds in
      morphine-dependent rats. These data provide the first empirical verification that
      conditioned nicotine withdrawal may occur after exposure to withdrawal-paired
      cues. Moreover, these data demonstrate that withdrawal-paired conditioned stimuli
      attain negative affective valence and can decrease the activity of brain reward
      systems, mimicking the reward deficit observed during withdrawal from nicotine
      and other addictive drugs.

PMID- 15987951
TI  - Treatment with an amyloid-beta antibody ameliorates plaque load, learning
      deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer's
      disease.
AB  - PDAPP transgenic mice overexpress a mutant form of human amyloid precursor
      protein under control of the platelet-derived growth factor promoter in CNS
      neurons that causes early onset, familial Alzheimer's disease in humans. These
      mice, on a mixed genetic background, have been shown to have substantial learning
      impairments from early ages, as well as an age-dependent decline in learning
      ability that has been hypothesized to be caused by amyloid-beta (Abeta)
      accumulation. The goals of this study were to determine: (1) whether PDAPP mice
      on a pure C57BL/6 background develop more severe age-dependent learning deficits
      than wild-type mice; (2) if so, whether Abeta accumulation accounts for the
      excessive decline in learning ability; and (3) whether the learning deficits are
      reversible, even after significant Abeta deposition. At 4-6, 10-12, or 17-19
      months of age, PDAPP and littermate wild-type mice on a C57BL/6 background were
      tested on a 5 week water maze protocol in which the location of the escape
      platform changed weekly, requiring the mice to repeatedly learn new information.
      PDAPP mice exhibited impaired spatial learning as early as 4 months (pre-Abeta
      deposition), and the performance of both wild-type and PDAPP mice declined with
      age. However, PDAPP mice exhibited significantly greater deterioration with age.
      Direct evidence for the role of Abeta accumulation in the age-related worsening
      in PDAPP mice was provided by the observation that systemic treatment over
      several weeks with the anti-Abeta antibody 10D5 reduced plaque deposition,
      increased plasma Abeta, improved hippocampal long-term potentiation, and improved
      behavioral performance in aged PDAPP mice with substantial Abeta burden.

PMID- 15987952
TI  - Presynaptic regulation of quantal size by the vesicular glutamate transporter
      VGLUT1.
AB  - A fundamental question in synaptic physiology is whether the unitary strength of
      a synapse can be regulated by presynaptic characteristics and, if so, what those
      characteristics might be. Here, we characterize a newly proposed mechanism for
      altering the strength of glutamatergic synapses based on the recently identified
      vesicular glutamate transporter VGLUT1. We provide direct evidence that filling
      in isolated synaptic vesicles is subject to a dynamic equilibrium that is
      determined by both the concentration of available glutamate and the number of
      vesicular transporters participating in loading. We observe that changing the
      number of vesicular transporters expressed at hippocampal excitatory synapses
      results in enhanced evoked and miniature responses and verify biophysically that
      these changes correspond to an increase in the amount of glutamate released per
      vesicle into the synaptic cleft. In addition, we find that this modulation of
      synaptic strength by vesicular transporter expression is endogenously regulated,
      both across development to coincide with a maturational increase in vesicle
      cycling and quantal amplitude and by excitatory and inhibitory receptor
      activation in mature neurons to provide an activity-dependent scaling of quantal
      size via a presynaptic mechanism. Together, these findings underscore that
      vesicular transporter expression is used endogenously to directly regulate the
      extent of glutamate release, providing a concise presynaptic mechanism for
      controlling the quantal efficacy of excitatory transmission during synaptic
      refinement and plasticity.

PMID- 15987953
TI  - Dopamine cells respond to predicted events during classical conditioning:
      evidence for eligibility traces in the reward-learning network.
AB  - Behavioral conditioning of cue-reward pairing results in a shift of midbrain
      dopamine (DA) cell activity from responding to the reward to responding to the
      predictive cue. However, the precise time course and mechanism underlying this
      shift remain unclear. Here, we report a combined single-unit recording and
      temporal difference (TD) modeling approach to this question. The data from
      recordings in conscious rats showed that DA cells retain responses to predicted
      reward after responses to conditioned cues have developed, at least early in
      training. This contrasts with previous TD models that predict a gradual stepwise
      shift in latency with responses to rewards lost before responses develop to the
      conditioned cue. By exploring the TD parameter space, we demonstrate that the
      persistent reward responses of DA cells during conditioning are only accurately
      replicated by a TD model with long-lasting eligibility traces (nonzero values for
      the parameter lambda) and low learning rate (alpha). These physiological
      constraints for TD parameters suggest that eligibility traces and low per-trial
      rates of plastic modification may be essential features of neural circuits for
      reward learning in the brain. Such properties enable rapid but stable initiation
      of learning when the number of stimulus-reward pairings is limited, conferring
      significant adaptive advantages in real-world environments.

PMID- 15987954
TI  - Mice with genetically altered glucocorticoid receptor expression show altered
      sensitivity for stress-induced depressive reactions.
AB  - Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the
      pathogenesis of major depression. To mimic the human situation of altered GR
      function claimed for depression, we generated mouse strains that underexpress or
      overexpress GR, but maintain the regulatory genetic context controlling the GR
      gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant
      mice (GR+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by
      a yeast artificial chromosome resulting in a twofold gene dose elevation. GR+/-
      mice exhibit normal baseline behaviors but demonstrate increased helplessness
      after stress exposure, a behavioral correlate of depression in mice. Similar to
      depressed patients, GR+/- mice have a disinhibited hypothalamic-pituitary-adrenal
      (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone
      test. Thus, they represent a murine depression model with good face and construct
      validity. Overexpression of GR in mice evokes reduced helplessness after stress
      exposure, and an enhanced HPA system feedback regulation. Therefore, they may
      represent a model for a stress-resistant strain. These mouse models can now be
      used to study biological changes underlying the pathogenesis of depressive
      disorders. As a first potential molecular correlate for such changes, we
      identified a downregulation of BDNF protein content in the hippocampus of GR+/-
      mice, which is in agreement with the so-called neurotrophin hypothesis of
      depression.

PMID- 15987955
TI  - Brain-derived neurotrophic factor is required for the establishment of the proper
      number of dopaminergic neurons in the substantia nigra pars compacta.
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in regulating
      neuronal survival, differentiation, and synaptic plasticity. Reduced expression
      of BDNF within the substantia nigra accompanies the deterioration of dopaminergic
      neurons in Parkinson's disease (PD) patients. Analysis of the effects of long
      term BDNF absence from the CNS has been difficult because of the early postnatal
      lethality of BDNF-/- mice. Mice with a floxed BDNF allele were bred with Wnt1-Cre
      mice to generate Wnt-BDNF(KO) mice that lack BDNF from the midbrain-hindbrain
      (MHB). These mice are viable but exhibit hindlimb clutching and poor rotarod
      performance. Tyrosine hydroxylase (TH)-positive neuron numbers in the substantia
      nigra pars compacta (SNC) were estimated using stereological methods, revealing a
      persistent approximately 23% reduction of these cells at postnatal day 21 (P21)
      in Wnt-BDNF(KO) mice compared with controls. The diminishment of TH-expressing
      neurons was present at birth and continued through P120. This deficit appears
      selective for the dopaminergic population, because at P21, total neuron number
      within the SNC, defined as neuronal nuclei protein-positive cells, was not
      significantly reduced. Interestingly, and similar to observations in PD patients,
      SNC neuron subpopulations are not equally affected. Calbindin- and calretinin
      expressing SNC populations show no significant difference between Wnt-BDNF(KO)
      mice and controls. Thus, BDNF depletion from the MHB selectively leads to reduced
      TH expression in a subpopulation of neurons, but it remains unclear whether these
      cells are lost.

PMID- 15987956
TI  - ALG9 mannosyltransferase is involved in two different steps of lipid-linked
      oligosaccharide biosynthesis.
AB  - N-linked protein glycosylation follows a conserved pathway in eukaryotic cells.
      The assembly of the lipid-linked core oligosaccharide Glc3Man9GlcNAc2, the
      substrate for the oligosaccharyltransferase (OST), is catalyzed by different
      glycosyltransferases located at the membrane of the endoplasmic reticulum (ER).
      The substrate specificity of the different glycosyltransferase guarantees the
      ordered assembly of the branched oligosaccharide and ensures that only completely
      assembled oligosaccharide is transferred to protein. The glycosyltransferases
      involved in this pathway are highly specific, catalyzing the addition of one
      single hexose unit to the lipid-linked oligosaccharide (LLO). Here, we show that
      the dolichylphosphomannose-dependent ALG9 mannosyltransferase is the exception
      from this rule and is required for the addition of two different alpha-1,2-linked
      mannose residues to the LLO. This report completes the list of lumen-oriented
      glycosyltransferases required for the assembly of the LLO.

PMID- 15987957
TI  - Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N
      acetylmannosamine kinase activities in human hereditary inclusion body myopathy.
AB  - Hereditary inclusion body myopathy (HIBM) is an autosomal recessive neuromuscular
      disorder associated with mutations in uridine diphosphate (UDP)-N
      acetylglucosamine (GlcNAc) 2-epimerase (GNE)/N-acetylmannosamine (ManNAc) kinase
      (MNK), the bifunctional and rate-limiting enzyme of sialic acid biosynthesis. We
      developed individual GNE and MNK enzymatic assays and determined reduced
      activities in cultured fibroblasts of patients, with HIBM harboring missense
      mutations in either or both the GNE and MNK enzymatic domains. To assess the
      effects of individual mutations on enzyme activity, normal and mutated GNE/MNK
      enzymatic domains were synthesized in a cell-free in vitro transcription
      translation system and subjected to the GNE and MNK enzymatic assays. This cell
      free system was validated for both GNE and MNK activities, and it revealed that
      mutations in one enzymatic domain (in GNE, G135V, V216A, and R246W; in MNK,
      A631V, M712T) affected not only that domain's enzyme activity, but also the
      activity of the other domain. Moreover, studies of the residual enzyme activity
      associated with specific mutations revealed a discrepancy between the fibroblasts
      and the cell-free systems. Fibroblasts exhibited higher residual activities of
      both GNE and MNK than the cell-free system. These findings add complexity to the
      tightly regulated system of sialic acid biosynthesis. This cell-free approach can
      be applied to other glycosylation pathway enzymes that are difficult to evaluate
      in whole cells because their substrate specificities overlap with those of
      ancillary enzymes.

PMID- 15987958
TI  - Science to practice: can multi-detector row spiral CT be used to assess left
      ventricular function?

PMID- 15987959
TI  - CT colonography reporting and data system: a consensus proposal.

PMID- 15987960
TI  - Idiopathic interstitial pneumonias: CT features.
AB  - Idiopathic interstitial pneumonias comprise usual interstitial pneumonia (UIP),
      nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia
      (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD),
      cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP), and
      lymphoid interstitial pneumonia (LIP). Each of these entities has a typical
      imaging and histologic pattern, although in practice the imaging patterns may be
      variable. Each entity may be idiopathic or may be secondary to a recognizable
      cause such as collagen vascular disease or inhalational exposure. The diagnosis
      of idiopathic interstitial pneumonia is made by means of correlation of clinical,
      imaging, and pathologic features. The characteristic computed tomographic (CT)
      features of UIP are predominantly basal and peripheral reticular pattern with
      honeycombing and traction bronchiectasis. NSIP is characterized by predominantly
      basal ground-glass opacity and/or reticular pattern, often with traction
      bronchiectasis. DIP and RB-ILD are smoking-related lung diseases characterized by
      ground-glass opacity and centrilobular nodules. COP is characterized by patchy
      peripheral or peribronchovascular consolidation. AIP manifests as diffuse lung
      consolidation and ground-glass opacity. LIP is associated with a CT pattern of
      ground-glass opacity sometimes associated with perivascular cysts.

PMID- 15987961
TI  - Does litigation influence medical practice? The influence of community
      radiologists' medical malpractice perceptions and experience on screening
      mammography.
AB  - PURPOSE: To assess the relationship between radiologists' perception of and
      experience with medical malpractice and their patient-recall rates in actual
      community-based clinical settings. MATERIALS AND METHODS: All study activities
      were approved by the institutional review boards of the involved institutions,
      and patient and radiologist informed consent was obtained where necessary. This
      study was performed in three regions of the United States (Washington, Colorado,
      and New Hampshire). Radiologists who routinely interpret mammograms completed a
      mailed survey that included questions on demographic data, practice environment,
      and medical malpractice. Survey responses were linked to interpretive performance
      for all screening mammography examinations performed between January 1, 1996, and
      December 31, 2001. The odds of recall were modeled by using logistic regression
      analysis based on generalized estimating equations that adjust for study region.
      RESULTS: Of 181 eligible radiologists, 139 (76.8%) returned the survey with full
      consent. The analysis included 124 radiologists who had interpreted a total of
      557 143 screening mammograms. Approximately half (64 of 122 [52.4%]) of the
      radiologists reported a prior malpractice claim, with 18 (14.8%) reporting
      mammography-related claims. The majority (n = 51 [81.0%]) of the 63 radiologists
      who responded to a question regarding the degree of stress caused by a medical
      malpractice claim described the experience as very or extremely stressful. More
      than three of every four radiologists (ie, 94 [76.4%] of 123) expressed concern
      about the impact medical malpractice has on mammography practice, with over half
      (72 [58.5%] of 123) indicating that their concern moderately to greatly increased
      the number of their recommendations for breast biopsies. Radiologists' estimates
      of their future malpractice risk were substantially higher than the actual
      historical risk. Almost one of every three radiologists (43 of 122 [35.3%]) had
      considered withdrawing from mammogram interpretation because of malpractice
      concerns. No significant association was found between recall rates and
      radiologists' experiences or perceptions of medical malpractice. CONCLUSION: U.S.
      radiologists are extremely concerned about medical malpractice and report that
      this concern affects their recall rates and biopsy recommendations. However,
      medical malpractice experience and concerns were not associated with recall or
      false-positive rates. Heightened concern of almost all radiologists may be a key
      reason that recall rates are higher in the United States than in other countries,
      but this hypothesis requires further study.

PMID- 15987962
TI  - Assessment of mitral valve regurgitation at electron-beam CT: comparison with
      Doppler echocardiography.
AB  - PURPOSE: To prospectively compare mitral valve regurgitation fractions calculated
      at electron-beam computed tomography (CT) (Doppler echocardiography as reference
      standard) and to evaluate accuracy of electron-beam CT volume and flow
      measurements compared with magnetic resonance (MR) imaging results. MATERIALS AND
      METHODS: Institutional review board approval and informed consent were obtained.
      Volume and flow measurements were performed at electron-beam CT in 219 patients
      (197 men, 22 women; mean age, 61.5 years +/- 10.4 [standard deviation]), of whom
      157 had known isolated mitral valve regurgitation. Regurgitation volume was
      calculated as the difference between left ventricular total and forward stroke
      volumes. Regurgitation fractions were compared with corresponding
      echocardiographic grades (grades 0-IV) by using Spearman rank correlation and a
      weighted kappa test. In 22 patients, CT volume and flow measurements were
      compared with MR results by using intraclass correlation. RESULTS: Regurgitation
      fractions at CT correlated well with echocardiographic grading (rank correlation
      coefficient, r(S) = 0.82; P < .05). Mean regurgitation fractions for
      echocardiographic grades 0, I, II, III, and IV were 3.1% +/- 6.2, 12.7% +/- 9.9,
      25.3% +/- 12.3, 40.4% +/- 11.5, and 55.9% +/- 13.7, respectively. The most
      suitable thresholds for differentiating echocardiographic grades were calculated
      regurgitation fractions of 6%, 20%, 30%, and 44%; with these thresholds,
      individual echocardiographic grades were differentiated (grades 0 vs I-IV, 0-I vs
      II-IV, 0-II vs III-IV, and 0-III vs IV, respectively) with sensitivities of 89%,
      87%, 86%, and 93% and specificities of 81%, 87%, 92%, and 91%, respectively.
      There was perfect agreement in classification of mitral valve insufficiency
      between electron-beam CT and echocardiography in 134 (61%) patients and a
      mismatch by one grade in 72 (33%) and by two grades in 13 (6%) (kappa = 0.84).
      Intraclass correlation coefficients between CT and MR imaging for total and
      forward stroke volumes and regurgitation volume and fraction were 0.88, 0.79,
      0.93, and 0.89, respectively. CONCLUSION: Electron-beam CT provides quantitative
      information on severity of mitral valve regurgitation, but semiquantitative
      classification of regurgitation showed mismatch between electron-beam CT and
      Doppler echocardiography by at least one grade in more than one-third of all
      patients.

PMID- 15987963
TI  - Aortoiliac occlusive disease in patients with known or suspected peripheral
      vascular disease: safety and efficacy of gadofosveset-enhanced MR angiography-
      multicenter comparative phase III study.
AB  - PURPOSE: To prospectively determine the safety and efficacy of the gadolinium
      based blood pool magnetic resonance (MR) imaging contrast agent gadofosveset in
      patients known to have or suspected of having peripheral vascular disease.
      MATERIALS AND METHODS: Ethical committee approval and patient written informed
      consent were obtained. This study was compliant with the Health Insurance
      Portability and Accountability Act. Adults known or suspected to have peripheral
      vascular disease received gadofosveset (0.03 mmol per kilogram of body weight)
      for MR angiography of the aortoiliac region. Gadofosveset-enhanced MR angiography
      and unenhanced two-dimensional time-of-flight MR angiography were compared with
      the reference standard, conventional angiography, for the presence of vascular
      stenosis. All patients were monitored for adverse events with hematologic
      analysis, analysis of blood chemistry, urinalysis, and electrocardiographic
      parameters; these methods were analyzed to determine safety. RESULTS: A total of
      274 patients were enrolled at 37 centers. Gadofosveset-enhanced MR angiography
      showed significant improvement (P < .001) compared with unenhanced MR angiography
      for each of the readers for diagnosis of clinically significant (> or = 50%)
      stenosis. Specificity and accuracy were significantly greater for three readers,
      and sensitivity increased significantly for two readers. For all readers, the
      area under the receiver operator characteristic curve for both quantitative and
      qualitative measures of significant disease increased (P < .001) for gadofosveset
      enhanced MR angiography versus two-dimensional time-of-flight MR angiography. All
      readers also expressed more confidence in diagnosis (P < .001) and found fewer
      images to be uninterpretable (0.5% vs 11.0%). The most common adverse events were
      as follows: feeling hot, 12 (4.4%) patients; nausea, 10 (3.6%) patients;
      headache, nine (3.3%) patients; and burning sensation, eight (2.9%) patients.
      Only four serious adverse events were reported, in three patients, and all events
      were rated as unlikely related to the drug. No patients were excluded because of
      adverse events or laboratory abnormalities. There were no clinically important
      trends in the findings of hematologic analysis, blood chemistry, urinalysis,
      electrocardiography, or physical examination. CONCLUSION: On the basis of
      substantial improvements over non-contrast MR angiography in efficacy and a
      minimal and transient side-effect profile, gadofosveset was found to be safe and
      effective for MR angiography in patients known or suspected to have peripheral
      vascular disease.

PMID- 15987965
TI  - Case 84: desmoid tumor of the abdominal wall.

PMID- 15987966
TI  - Role of US in detection of Crohn disease: meta-analysis.
AB  - PURPOSE: To evaluate the accuracy of ultrasonography (US) in the detection of
      Crohn disease in adults by systematically reviewing both cohort studies (those
      including patients whose clinical characteristics were consistent with those
      caused by an inflammatory bowel disease) and case-control studies (those in which
      patients with Crohn disease were compared with patients with other bowel diseases
      or healthy control subjects). MATERIALS AND METHODS: The MEDLINE, EMBASE, and
      Cochrane Library databases were used to retrieve all the cross-sectional studies
      that assessed the diagnostic accuracy of US against that of one of several
      predefined reference standards (ie, radiologic, endoscopic, or histologic
      findings). The studies that fulfilled the inclusion criteria were identified, and
      their methodological quality was evaluated. Of the 2860 primary studies
      identified, two case-control and five cohort series fulfilled the inclusion
      criteria. Statistical analysis was performed by using the summary receiver
      operating characteristic (SROC) model. RESULTS: The ranges of US sensitivity and
      specificity for the diagnosis of Crohn disease reported for the included series
      were 75%-94% and 67%-100%, respectively; the heterogeneity of these values
      prevented the calculation of a cumulative value. The SROC curve revealed a clear
      cutoff effect that depended on the chosen bowel wall thickness threshold.
      Sensitivity and specificity of 88% and 93%, respectively, were achieved when a
      bowel wall thickness threshold greater than 3 mm was used, and sensitivity and
      specificity of 75% and 97%, respectively, were achieved when a threshold greater
      than 4 mm was used. CONCLUSION: US examination seems appropriate for confirming
      or excluding Crohn disease as a diagnosis in a clinical context characterized by
      a pretest probability of Crohn disease that ranges from 12% to about 60%. In
      particular, for Crohn disease limited to the ileum, US may represent a valid
      alternative to the small-bowel series, while for colonic involvement US may be
      useful in ruling out the diagnosis.

PMID- 15987967
TI  - Polyp size at CT colonography after electronic subtraction cleansing in an
      anthropomorphic colon phantom.
AB  - PURPOSE: To evaluate the effect of various bowel contrast material concentrations
      and subtraction software on size measurements of well-defined polyp lesions in a
      colon phantom at CT colonography. MATERIALS AND METHODS: Repeated scanning and a
      precise reference standard required the use of a colon phantom in which 21 polyps
      were randomly distributed. Two readers who had each reviewed computed tomographic
      (CT) colonographic images from more than 100 cases evaluated polyp size on images
      obtained when the phantom was partially filled with varying concentrations of
      contrast material, scanned by using CT colonography, and subjected to electronic
      subtraction cleansing. The single largest dimension was recorded for each reader
      for a randomized series of polyps. These measurements were compared with a
      reference standard that was based on a combination of the manufacturer's polyp
      size specifications and the subsequent verification of these sizes by an
      independent consensus panel. Six weeks after initial observations, readers
      evaluated images of the phantom scanned without the presence of contrast
      material. Polyp size estimations for the two readers for each series were
      compared with the reference standard to obtain a mean absolute measurement error
      for each reader for each series. Data for each reader were compared by using a
      nonparametric Kruskal-Wallis analysis of variance test. A pair-wise comparison of
      the experimental and control series was then performed by using the Dunn post hoc
      test. RESULTS: Contrast material dilutions resulting in an average attenuation of
      less than 500 HU resulted in complete subtraction and the absence of streak
      artifacts. There was no statistically significant difference between the average
      measurement error for contrast attenuations between 300 and 500 HU when compared
      with that of control. Streak artifact was noticeable for the highest dilution
      (mean, 840 HU). No statistically significant differences were observed for series
      in which cleansing software was used in the absence of bowel contrast material.
      CONCLUSION: The combination of electronic cleansing and bowel contrast
      enhancement in the range of 300-500 HU results in no substantial change in
      readers' estimations of polyp size at CT colonography.

PMID- 15987968
TI  - Hepatic hemorrhage caused by percutaneous tumor ablation: radiofrequency ablation
      versus cryoablation in a porcine model.
AB  - PURPOSE: To determine the extent of hepatic hemorrhage caused by percutaneous
      cryoablation performed with a small-diameter cryoablation probe compared with
      that caused by percutaneous radiofrequency (RF) ablation in a porcine model.
      MATERIALS AND METHODS: The study was pre-approved by the institutional research
      animal care and use committee, and husbandry and experiments complied with
      National Institutes of Health standards for care and use of laboratory animals.
      Percutaneous hepatic ablation was performed in 18 domestic pigs (mean weight, 45
      kg) by using a 17-gauge (1.5-mm-diameter) RF electrode (n = 6), a cluster of
      three RF electrodes (n = 6), or a 13-gauge (2.4 mm-diameter) cryoprobe (n = 6).
      Ablation was performed in four sites per liver. Total blood loss, minimum lesion
      diameter, maximum lesion diameter, and lesion volume were determined for each
      group and compared by using analysis of variance. RESULTS: Mean blood loss was
      11.11 mL +/- 11.47 (standard deviation), 105.29 mL +/- 175.58, and 28.06 mL +/-
      30.97 with the single RF electrode, RF electrode cluster, and cryoablation probe,
      respectively. Mean minimum and maximum lesion diameters were largest with the RF
      electrode cluster (2.40 and 3.98 cm, respectively), followed by the cryoablation
      probe (2.38 and 3.94 cm) and single RF electrode (1.49 and 2.63 cm). Mean minimum
      and maximum lesion diameters were significantly different between the single RF
      electrode and the RF electrode cluster, as well as between the single RF
      electrode and the cryoablation probe (P < .001). Mean lesion volume was largest
      for the RF electrode cluster (24.03 cm3), followed by those for the cryoablation
      probe (17.46 cm3) and single RF electrode (9.05 cm3) (single RF electrode vs
      cryoablation probe, P < .05). Lesion volumes were not significantly different
      with the RF electrode cluster versus the single RF electrode (P = .052) or with
      the RF electrode cluster versus the cryoablation probe (P = .381). CONCLUSION:
      Mean blood loss from percutaneous cryoablation in this model was between that for
      RF ablation with the single electrode and that for RF ablation with the electrode
      cluster.

PMID- 15987969
TI  - Radiofrequency versus microwave ablation in a hepatic porcine model.
AB  - PURPOSE: To compare microwave (MW) and radiofrequency (RF) ablation in a hepatic
      porcine model. MATERIALS AND METHODS: Institutional animal research committee
      approval was obtained. Nineteen pigs were divided into groups based on time of
      sacrifice (group A, immediate; group B, 2 days; group C, 28 days; group D, 28
      days). Groups A, B, and C each underwent a combination of RF and MW ablation.
      Group D underwent either four MW or four RF ablations. Ablation was performed
      with a prototype MW device (915 Mhz, 40 W, 10 minutes) and a commercial RF system
      (150 W, 10 minutes, 3-cm deployment). Computed tomography (CT) was performed in
      groups B and C at 2 days and in group C at 28 days. Group D underwent serial
      laboratory testing. Specimens were serially sectioned, and short-axis diameter
      and length of each were measured. The percentage deflection caused by local blood
      vessels (heat-sink effect) was also measured in group A. Likelihood ratio tests
      and unpaired t tests were used for statistical analyses as appropriate. RESULTS:
      MW ablation zones were longer at days 0, 2, and 28 (P < .05), but short-axis
      diameter was not different from that with RF ablation at any time point (P >
      .05). Local blood vessels caused 3.5% +/- 5.3 (standard deviation) deflection at
      MW ablation compared with 26.2% +/- 27.9 at RF ablation (P < .05). MW and RF
      ablation zones were indistinguishable at CT or pathologic evaluation. Laboratory
      test results were similar between RF ablation-only animals and MW ablation-only
      animals, with the exception of a slightly higher alkaline phosphatase levels at
      day 2 in RF ablation-only animals (P < .02). CONCLUSION: MW and RF ablation zones
      are similar in pathologic appearance and imaging characteristics. Increased
      length with MW ablation is likely caused by the length of the radiating segment
      of the antenna. MW ablation may be less affected by the heat-sink effect that is
      thought to contribute to local recurrence after RF ablation.

PMID- 15987970
TI  - Cartilage MR imaging at 3.0 versus that at 1.5 T: preliminary results in a
      porcine model.
AB  - PURPOSE: To compare 1.5- and 3.0-T magnetic resonance (MR) images of porcine knee
      specimens containing artificial cartilage lesions in terms of accuracy of lesion
      depiction, image quality, and signal-to-noise ratio (SNR). MATERIALS AND METHODS:
      This Health Insurance Portability and Accountability Act-compliant study had
      institutional review board approval, and informed consent was obtained from the
      human volunteers. Two fat-saturated cartilage MR imaging sequences (an
      intermediate-weighted fast spin-echo [SE] sequence and a spoiled gradient-echo
      [GRE] sequence) were optimized for imaging at 3.0 T in two human volunteers and
      then used to image 10 porcine knees in which 29 artificial cartilage lesions had
      been created. Corresponding sequences were used at 1.5 T for all specimens.
      Images were assessed by two radiologists in consensus, and diagnostic performance
      in lesion depiction was determined by using macroscopic findings in specimen
      slices as a reference standard. SNRs were also calculated. For statistical
      analysis, the McNemar test of discordant pairs was used with a level of
      significance of P < .05. RESULTS: The best diagnostic performance for both the
      intermediate-weighted fast SE and the spoiled GRE sequences was achieved at 3.0
      T. With use of corresponding fat-saturated intermediate-weighted fast SE
      sequences with an identical acquisition time (9 minutes 44 seconds), 26 (90%) of
      29 lesions were detected at 3.0 T, while 18 (62%) were detected at 1.5 T. With
      use of fat-saturated spoiled GRE sequences, 24 (83%) of 29 lesions were detected
      at 3.0 T (acquisition time, 8 minutes 48 seconds), and 23 (79%) lesions were
      detected at 1.5 T (acquisition time, 11 minutes 14 seconds). The rate of correct
      lesion grade assessment was 65% (17 of 26 lesions) at 3.0 T and 61% (11 of 18
      lesions) at 1.5 T with the intermediate-weighted fast SE sequences and 83% (20 of
      24 lesions) at 3.0 T and 70% (16 of 23 lesions) at 1.5 T with the spoiled GRE
      sequences. Both subjective evaluation of image quality and SNR values were
      significantly higher at 3.0 T (P < .05). CONCLUSION: In this animal model, MR
      imaging at 3.0 T increased the accuracy of cartilage lesion assessment when
      compared with imaging at 1.5 T. Image quality and SNR were highest at 3.0 T.

PMID- 15987971
TI  - Chitin-based embolic materials in the renal artery of rabbits: pathologic
      evaluation of an absorbable particulate agent.
AB  - PURPOSE: To prospectively evaluate the tissue reaction to and the embolic effect
      and absorption of chitin and chitosan microspheres and polyvinyl alcohol (PVA) in
      the renal artery of rabbits. MATERIALS AND METHODS: This experiment was performed
      in accordance with regulations on animal care and experiments. Thirty-six New
      Zealand white rabbits were divided into four groups according to the materials
      (PVA, chitin particles, and chitosan particles, and chitosan microspheres;
      diameter, 150-250 microm) used for embolization of the right renal artery. A
      rabbit from each group was sacrificed 1 and 3 days and 1, 2, 4, 8, 16, 24, and 32
      weeks after embolization. Gross and microscopic pathologic findings were examined
      with hematoxylin-eosin, Masson trichrome, and Victoria blue staining. RESULTS:
      Gross pathologic findings were examined, and swelling of embolized kidneys was
      observed 1 and 3 days after embolization, whereas shrinkage of the embolized
      kidneys was consistently seen after 2 weeks, with a hard consistency and nodular
      surfaces being noted. At histologic analysis, chitosan microspheres filled the
      lumen more compactly than did other particles. With PVA, a large amount of
      capillary formations occurred within the embolized arteries, whereas chitin
      particles and chitosan microspheres showed a lower rate of capillary formation.
      The shape of all embolic materials remained intact until week 8, at which time
      the materials gradually decreased in size and number. The chitosan particles and
      the chitosan microspheres were absorbed around weeks 16 and 24, respectively.
      CONCLUSION: Chitosan microspheres have great potential as a new embolic material
      since they block blood vessels more compactly with a lower rate of capillary
      formation. This material is biocompatible, and it is absorbed 24 weeks after
      embolization.

PMID- 15987972
TI  - Spasmolysis at CT colonography: butyl scopolamine versus glucagon.
AB  - PURPOSE: To retrospectively determine if the use of butyl scopolamine or glucagon
      in the supine patient improves colonic distention and reduces the number of
      collapsed intestinal segments at computed tomographic (CT) colonography.
      MATERIALS AND METHODS: This study had institutional review board approval;
      subject informed consent was not required. CT colonography was performed without
      the administration of an intravenous spasmolytic in 80 asymptomatic subjects
      (group 1; 45 women, 35 men; age range, 48-77 years; mean, 61.9 years). These
      subjects were matched with two groups of 80 subjects who were similar in age but
      were premedicated with glucagon (group 2; 41 women, 39 men; age range, 43-76
      years; mean, 63.1 years) or butyl scopolamine (group 3; 43 women, 37 men; age
      range, 34-77 years; mean, 63.4 years). All 240 subjects were examined in the
      supine position with multisection CT and a section thickness of 1 mm after
      intravenous contrast agent administration and rectal carbon dioxide insufflation.
      The colon was divided into seven segments, and the colon length, total volume,
      radial distensibility, and number of non-distended segments were calculated for
      each subject and compared among the three groups. Statistical analysis was
      performed with analysis of variance and chi2 testing. RESULTS: Mean bowel length
      was not significantly different among the groups. Mean colon volumes and radial
      distensibilities, respectively, were 1.84 L and 3.69 cm in group 1, 2.14 L and
      3.98 cm in group 2, and 2.35 L and 4.23 cm in group 3; differences in colon
      volume and radial distensibility were significant only between group 1 and group
      3 (P < .001). At CT colonography, 29 segments in 20 group 1 subjects were
      collapsed, 23 segments in 12 group 2 subjects were collapsed, and 11 segments in
      six group 3 subjects were collapsed (P = .016). CONCLUSION: Premedication with
      butyl scopolamine or, less effectively, glucagon improves colonic distention in
      the supine subject.

PMID- 15987973
TI  - Functional renal volume: quantitative analysis at gadolinium-enhanced MR
      angiography--feasibility study in healthy potential kidney donors.
AB  - PURPOSE: To assess the feasibility of quantifying functional renal volume with
      gadolinium-enhanced magnetic resonance (MR) angiography. MATERIALS AND METHODS:
      Institutional review board approval was obtained, and all subjects gave informed
      consent. A contour-detection three-dimensional algorithm for determining renal
      volumes was developed. The method was validated in 18 cadaveric pig kidneys by
      measuring the water displacement caused by the kidneys. The kidney lengths and
      volumes in 19 consecutive potential kidney donors who underwent gadolinium
      enhanced MR angiography of the renal arteries also were determined. Differences
      in volume measurements between men and women and between left and right kidneys
      were analyzed by using the Student t test. The volume of perfused renal cortex
      was calculated by extracting voxels on the basis of the cortex signal intensity
      threshold. The relevance of renal function parameters--namely, creatinine
      clearance rates--in the donor candidates was assessed by using a linear
      regression model. Intra- and interobserver variabilities of the measurements were
      determined by using the Bland-Altman method. RESULTS: Volume measurements of the
      cadaveric pig kidneys obtained by using MR angiography and the water displacement
      method were strongly correlated (r = 0.99). The mean total renal volume in the
      donor candidates was 196 mL (range, 136-295 mL). No significant differences in
      total renal volume between the men and women or between the left and right
      kidneys were found. The correlation between calculated renal cortex volumes
      (mean, 67 mL; range, 40-105 mL) and creatinine clearance rates was good (r =
      0.69). Inter- and intraobserver variabilities were lower than 7%. CONCLUSION:
      Quantification of functional renal volume with three-dimensional gadolinium
      enhanced MR angiography seems feasible with use of the described semiautomatic
      method.

PMID- 15987974
TI  - Uterine fibroids: diffusion-weighted MR imaging for monitoring therapy with
      focused ultrasound surgery--preliminary study.
AB  - PURPOSE: To prospectively determine the feasibility of using diffusion-weighted
      (DW) imaging and apparent diffusion coefficient (ADC) mapping before (baseline)
      and after treatment and at 6-month follow-up to monitor magnetic resonance (MR)
      image-guided focused ultrasound surgical ablation of uterine fibroids. MATERIALS
      AND METHODS: Informed consent was obtained from patients before treatment with
      our study protocol, as approved by the institutional review board, and the study
      complied with the Health Insurance Portability and Accountability Act. Fourteen
      patients (mean age, 46 years +/- 5 [standard deviation]) who underwent DW imaging
      were enrolled in this study, and 12 of 14 completed the inclusive MR examination
      with DW imaging at 6-month follow-up. Treatment was performed by one radiologist
      with a modified MR image-guided focused ultrasound surgical system coupled with a
      1.5-T MR imager. Pre- and posttreatment and 6-month follow-up MR images were
      obtained by using phase-sensitive T1-weighted fast spoiled gradient-recalled
      acquisition, T1-weighted contrast material-enhanced, and DW imaging sequences.
      Total treatment time was 1-3 hours. Trace ADC maps were constructed for
      quantitative analysis. Regions of interest localized to areas of hyperintensity
      on DW images were drawn on postcontrast images, and quantitative statistics were
      obtained from treated and nontreated uterine tissue before and after treatment
      and at 6-month follow-up. Statistical analysis was performed with analysis of
      variance. Differences with P < .05 were considered statistically significant.
      RESULTS: T1-weighted contrast-enhancing fibroids selected for treatment had no
      hyperintense or hypointense signal intensity changes on the DW images or ADC maps
      before treatment. Considerably increased signal intensity changes that were
      localized within the treated areas were noted on DW images. Mean baseline ADC
      value in fibroids was 1504 mm(-6)/sec2 +/- 290. Posttreatment ADC values for
      nontreated fibroid tissue (1685 mm(-6)/sec2 +/- 468) differed from posttreatment
      ADC values for fibroid tissue (1078 mm(-6)/sec2 +/- 293) (P = .001). A
      significant difference (P < .001) between ADC values for treated (1905 mm(
      6)/sec2 +/- 446) and nontreated (1437 mm(-6)/sec2 +/- 270) fibroid tissue at 6
      month follow-up was observed. CONCLUSION: DW imaging and ADC mapping are feasible
      for identification of ablated tissue after focused ultrasound treatment of
      uterine fibroids.

PMID- 15987975
TI  - Krabbe disease treated with hematopoietic stem cell transplantation: serial
      assessment of anisotropy measurements--initial experience.
AB  - PURPOSE: To prospectively compare diffusion-tensor magnetic resonance (MR)
      imaging anisotropy measurements of white matter (WM) regions in early and late
      treatment groups of Krabbe disease patients treated with stem cell
      transplantation. MATERIALS AND METHODS: The study was approved by the
      Institutional Review Board and was compliant with Health Insurance Portability
      and Accountability Act; informed consent was obtained from the families of all
      patients. Patients with early-onset Krabbe disease (four girls and three boys)
      underwent diffusion-tensor MR imaging before and after stem cell transplantation.
      Fractional anisotropy (FA) values from serial studies were compared in patients
      who underwent transplantation at less than 1 month (early group, two girls and
      one boy) and those who underwent transplantation at 5-8 months (late group, two
      girls and two boys). FA values were measured in the genu and splenium of the
      corpus callosum, the frontal WM, and the internal capsule; were compared with
      those of five age-matched children in the comparison group (normal MR images and
      no proved neurologic disease); and were expressed as a ratio. Images obtained
      after transplantation were evaluated at approximately 1 (n = 7), 2 (n = 6), 3 (n
      = 1), and 4 (n = 1) years. RESULTS: Before transplantation, mean FA ratios in the
      early group for all four WM regions ranged between 97% and 117%. At 1 year, mean
      FA ratios at all locations were either 92% or 93%. At 2 years after
      transplantation, mean FA ratios were between 83% and 92%. In one patient imaged
      at 3 years, the mean FA ratio was 97%; in another patient imaged at 4 years, the
      mean FA ratio was 77%. Before transplantation, mean FA ratios in the late group
      ranged between 55% and 74%. Mean FA ratios were between 37% and 50% at 1 year
      after transplantation and between 36% and 39% at 2 years. CONCLUSION: All
      patients had decreases in FA ratios over time. The early group had higher initial
      FA ratios and lower subsequent decreases, which may indicate amelioration of the
      dysmyelinating process.

PMID- 15987976
TI  - Reactive carpal synovitis: initial experience with MR imaging.
AB  - PURPOSE: To retrospectively evaluate the accuracy of various magnetic resonance
      (MR) imaging findings in the diagnosis of reactive carpal synovitis. MATERIALS
      AND METHODS: Institutional review board approval was obtained, and the need for
      informed consent was waived. This study was compliant with the Health Insurance
      Portability and Accountability Act. Thirty-five consecutive patients (19 male and
      16 female patients; age range, 13-57 years) who underwent arthroscopy and MR
      imaging within 4 weeks of surgery were evaluated by two reviewers for the
      following potential findings of synovitis: (a) distention of the pisotriquetral
      recess by fluid, (b) distention of the radial and/or prestyloid recess, (c)
      synovial enhancement (in patients who received contrast material), (d) amount of
      dorsal capsule distention, and (e) the location of bone marrow edema, if any. The
      chi2 and paired t tests were used to assess these findings in patients with and
      patients without arthroscopically proved synovitis. The sensitivity, specificity,
      positive and negative predictive values, and accuracy of these findings in the
      detection of synovitis were calculated. RESULTS: Fluid in the pisotriquetral
      recess was seen in nine of the 14 patients with synovitis and five of the 21
      patients without synovitis (P = .018). Distention of the radial and/or prestyloid
      recess was observed in six of the 14 patients with synovitis and two of the 21
      patients without synovitis (P = .027). Among the 24 patients who received
      contrast material, synovial enhancement was seen in seven of eight patients with
      synovitis and three of 16 patients without synovitis (P = .002). The dorsal
      capsule measured 1-7 mm (mean, 3.07 mm) in the 14 patients with synovitis and 2-7
      mm (mean, 3.76 mm) in the 21 patients without synovitis (P = .193). Although bone
      marrow edema was seen globally in similar frequencies (nine of 14 patients with
      synovitis, nine of 21 patients without synovitis), pisotriquetral bone marrow
      edema was seen only in patients with synovitis (two of nine patients).
      CONCLUSION: Fluid in the pisotriquetral recess, enhancing synovium, and, less
      commonly, pisotriquetral bone marrow edema are MR imaging findings that may help
      in the diagnosis of reactive carpal synovitis.

PMID- 15987977
TI  - Fibrocystic changes at anterosuperior femoral neck: prevalence in hips with
      femoroacetabular impingement.
AB  - PURPOSE: To retrospectively evaluate if there is an association between juxta
      articular fibrocystic changes at the anterosuperior femoral neck and
      femoroacetabular impingement (FAI). MATERIALS AND METHODS: The institutional
      review board approved this study and did not require informed patient consent. An
      orthopedic surgeon and a radiologist in consensus retrospectively reviewed the
      anteroposterior (AP) pelvic radiographs of 117 hips with FAI and compared these
      images with the AP radiographs of a control group of 132 hips with developmental
      dysplasia (DD) to determine the prevalence of juxta-articular fibrocystic changes
      at the anterosuperior femoral neck. Criteria for juxta-articular fibrocystic
      changes at the anterosuperior femoral neck were location close to the physis and
      a diameter (of the fibrocystic change) of greater than 3 mm. The sensitivity and
      specificity of AP pelvic radiography in the detection of these fibrocystic
      changes were calculated by using an additional 61 hips with FAI and on the basis
      of findings at magnetic resonance (MR) arthrography, which was routinely
      performed for assessment of FAI. In 24 patients who underwent joint-preserving
      surgery for FAI, the fibrocystic changes were localized intraoperatively and the
      spatial relation of the region of these changes to the area of FAI was
      identified. Joint-preserving surgery consisted of anterior surgical dislocation
      of the hip with osteochondroplasty of the proximal femur and/or the acetabular
      rim to improve the impingement-free range of hip motion. For statistical
      comparisons, nonparametric tests were performed. RESULTS: Fibrocystic changes
      were identified on the AP radiographs of 39 (33%) of the 117 FAI-affected hips
      and on none of the radiographs of the 132 DD-affected hips. According to MR
      arthrogram findings, the sensitivity, specificity, and positive and negative
      predictive values of AP pelvic radiography were 64%, 93%, 91%, and 71%,
      respectively. The mean diameter of the juxta-articular fibrocystic changes was 5
      mm (range, 3-15 mm); smaller lesions were more prevalent. Dynamic MR imaging with
      the hip flexed and intraoperative observations revealed a close spatial
      relationship between the region of the fibrocystic changes at the anterosuperior
      femoral neck and the acetabular rim. CONCLUSION: The high prevalence of juxta
      articular fibrocystic changes at the anterosuperior femoral neck and their
      spatial relation to the impingement site suggest an association and possible
      causal relationship between these alterations and FAI.

PMID- 15987978
TI  - Seizure disorders: functional MR imaging for diagnostic evaluation and surgical
      treatment--prospective study.
AB  - PURPOSE: To prospectively evaluate effect of functional magnetic resonance (MR)
      imaging on diagnostic work-up and treatment planning in patients with seizure
      disorders who are candidates for surgical treatment. MATERIALS AND METHODS:
      Institutional review board approval was obtained; informed consent was obtained
      either from the patient or the parent or guardian in all patients. This study was
      conducted with Health Insurance Portability and Accountability Act compliance.
      Sixty consecutively enrolled patients (33 males, 27 females; mean age, 15.8 years
      +/- 8.7 [standard deviation]; range, 6.8-44.2 years) were prospectively examined.
      Forty-five (75%) patients were right handed, nine (15%) were left handed, and six
      (10%) had indeterminate hand dominance. Prospective questionnaires were used to
      evaluate diagnostic work-up, counseling, and treatment plans of the seizure team
      before and after functional MR imaging. Confidence level scales were used to
      determine effect of functional MR imaging on diagnostic and therapeutic thinking.
      Paired t test and 95% confidence interval analyses were performed. RESULTS: In 53
      patients, language mapping was performed; in 33, motor mapping; and in seven,
      visual mapping. The study revealed change in anatomic location or lateralization
      of language-receptive (Wernicke) (28% of patients) and language-expressive
      (Broca) (21% of patients) areas. Statistically significant increases were found
      in confidence levels after functional MR imaging in regard to motor and visual
      cortical function evaluation. In 35 (58%) of 60 patients, the seizure team
      thought that functional MR imaging results altered patient and family counseling.
      In 38 (63%) of 60 patients, functional MR imaging results helped to avoid further
      studies, including Wada test. In 31 (52%) and 25 (42%) of 60 patients,
      intraoperative mapping and surgical plans, respectively, were altered because of
      functional MR imaging results. In five (8%) patients, two-stage surgery with
      extra-operative direct electrical stimulation mapping was averted, and resection
      was accomplished in one stage. In four (7%) patients, extent of surgical
      resection was altered because eloquent areas were identified close to seizure
      focus. CONCLUSION: Functional MR imaging results influenced diagnostic and
      therapeutic decision making of the seizure team; results indicated language
      dominance changed, confidence level in identification of critical brain function
      areas increased, patient and family counseling were altered, and intraoperative
      mapping and surgical approach were altered.

PMID- 15987979
TI  - Intracortical lesions in multiple sclerosis: improved detection with 3D double
      inversion-recovery MR imaging.
AB  - PURPOSE: To prospectively compare the depiction of intracortical lesions by using
      multislab three-dimensional (3D) double inversion-recovery (DIR), multislab 3D
      fluid-attenuated inversion-recovery (FLAIR), and T2-weighted spin-echo (SE)
      magnetic resonance (MR) imaging in patients with multiple sclerosis. MATERIALS
      AND METHODS: Local ethics review board approval and informed consent were
      obtained. Conventional T2-weighted SE and multislab 3D FLAIR and DIR images were
      acquired in 10 patients with multiple sclerosis (five women, five men) and 11 age
      matched healthy control subjects (seven women, four men). Mean age was 40 years
      (range, 25-54 years) in patients and 34 years (range, 24-55 years) in control
      subjects. Lesions were classified according to seven anatomic regions:
      intracortical, mixed white matter-gray matter, juxtacortical, deep gray matter,
      periventricular white matter, deep white matter, and infratentorial lesions. The
      numbers of lesions per category were compared between techniques (Dunnett
      corrected analysis of variance). Gain or loss (with 95% confidence intervals
      [CIs]) of numbers of lesions detected at 3D DIR imaging was calculated in
      comparison with those detected at T2-weighted SE and 3D FLAIR imaging. RESULTS:
      Total number of lesions did not differ between 3D DIR and 3D FLAIR sequences, but
      the 3D DIR sequence showed a gain of 21% (95% CI: 4%, 41%) in comparison with the
      T2-weighted SE sequence. Because of high gray matter-white matter contrast, DIR
      images depicted more intracortical lesions (80 lesions in 10 patients) than both
      SE (10 lesions) and FLAIR (31 lesions) images; gains with DIR were 538% (95% CI:
      191%, 1297%) and 152% (95% CI: 15%, 453%) compared with SE and FLAIR,
      respectively. Only four intracortical lesions were detected in control subjects.
      Also, DIR imaging enabled a better definition of mixed white matter-gray matter
      lesions because of greater contrast between the lesion and its surroundings.
      CONCLUSION: MR imaging with 3D DIR enables increased intracortical lesion
      detection in the multiple sclerosis brain, as well as improved distinction
      between juxtacortical and white matter-gray matter lesions.

PMID- 15987980
TI  - Focal uptake of fluorodeoxyglucose by the thyroid in patients undergoing initial
      disease staging with combined PET/CT for non-small cell lung cancer.
AB  - PURPOSE: To retrospectively evaluate the prevalence of focal fluorodeoxyglucose
      (FDG) uptake by the thyroid gland on combined positron emission tomographic (PET)
      and computed tomographic (CT) scans in patients undergoing staging of newly
      diagnosed non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      Institutional review board approval was obtained, informed consent was waived,
      and the study was Health Insurance Portability and Accountability Act-compliant.
      Whole-body PET/CT scans and medical records of 140 consecutive patients with
      newly diagnosed NSCLC (80 men, 60 women; mean age, 66 years; range, 39-89 years)
      were retrospectively reviewed by two experienced PET/CT scan readers. Maximum
      standardized uptake value (SUV) was calculated for FDG-avid thyroid foci.
      Corresponding thyroid CT findings were recorded in patients with focal increased
      FDG thyroid uptake. RESULTS: PET results showed that six patients (4.3%) had
      seven foci of increased FDG uptake in the thyroid. Five of the seven foci (in
      four patients) corresponded to a low-attenuation thyroid lesion on the non
      enhanced CT scan. Lesions ranged in diameter from 0.8 to 2.5 cm. Four of the
      lesions were found to be papillary thyroid cancers at fine-needle aspiration
      biopsy. The fifth lesion was found to be benign at thyroidectomy. The remaining
      two patients did not have histologic confirmation of their thyroid lesion because
      no specific biopsy site was visualized on CT or sonographic images and lesions
      were considered benign. Maximum SUV of the thyroid cancers ranged from 3.0 to
      32.9 (mean, 13.7). Maximum SUV of benign thyroid lesions ranged from 4.6 to 6.2
      (mean, 5.4). CONCLUSION: Focal thyroid FDG uptake found during the initial
      staging of NSCLC at PET/CT indicates a high likelihood of primary thyroid cancer.

PMID- 15987981
TI  - The thread and streak sign.

PMID- 15987982
TI  - Cardiovascular screening with parallel imaging techniques and a whole-body MR
      imager.
AB  - The purpose of this study was to integrate parallel acquisition techniques into a
      comprehensive whole-body cardiovascular screening protocol to image all relevant
      organ systems without compromising spatial or temporal resolution. The study was
      approved by the institutional review board, and oral and written informed consent
      was obtained from each subject. Fifty subjects underwent whole-body magnetic
      resonance imaging that included imaging of heart, blood vessels, brain, lungs,
      and abdominal organs with a standard eight-channel imager. Image quality and
      pathologic findings were evaluated by two readers. The same protocol was then
      implemented with a new 32-channel whole-body imager. Depiction of 1476 (73.2%) of
      2016 vessel segments was rated as good to excellent, and that of 1744 (86.5%), as
      without venous overlay. Interobserver agreement was good in evaluation of image
      quality and excellent in evaluation of pathologic findings. Acquisition time was
      reduced significantly (P < .05) with use of the whole-body imager and parallel
      acquisition techniques, which provided high-quality fast cardiovascular imaging.

PMID- 15987983
TI  - Multi-detector row CT pulmonary angiography: comparison of standard-dose and
      simulated low-dose techniques.
AB  - PURPOSE: To compare standard-dose and simulated low-dose multi-detector row
      computed tomography (CT) pulmonary angiography. MATERIALS AND METHODS: The
      institutional review board approved the study protocol and waived patient
      informed consent because the study was based on existing data. Raw data from 21
      CT scans obtained at 90 mAs (effective) in 11 women and 10 men aged 25-74 years
      (mean, 52 years) that showed at least one filling defect within a pulmonary
      artery were used to simulate CT pulmonary angiography with reduced radiation
      doses, at 60, 40, 20, and 10 mAs. Three independent readers coded each central
      and segmental pulmonary artery twice as positive, negative, or inconclusive for
      presence of a filling defect. The second reading of images obtained with 90 mAs
      was considered the reference standard. The potential dependence of results on
      reader, radiation dose, and/or pulmonary artery segment was investigated with
      analysis of variance. Positive and negative consistent values were calculated for
      standard-dose scans and simulated low-dose scans in the first reading session.
      The branching order of the artery with the most distal filling defect was
      recorded. The quality of intravascular contrast at each tube current-time product
      setting was scored on a five-point scale. Interreader agreement was investigated
      with kappa statistics. RESULTS: The frequencies of positive and inconclusive
      results (P = .21 and .08, respectively), positive and negative consistent values
      (P = .19 and .34, respectively), and branching order of the most distal artery
      with a filling defect (P = .41) did not depend on the radiation dose. Values for
      inter- and intrareader agreement were higher for central arterial segments than
      for branch arteries but were not influenced by dose reduction, regardless of
      arterial segment. The quality of intravascular contrast was not significantly
      changed when the tube current-time product was reduced from 90 to 40 mAs (P = .10
      to >.99). CONCLUSION: The evaluated parameters remained stable when tube current
      time product was reduced from 90 (effective) to 10 (simulated) mAs at multi
      detector row CT pulmonary angiography.

PMID- 15987984
TI  - Pulmonary cryptococcosis: CT findings in immunocompetent patients.
AB  - PURPOSE: To evaluate retrospectively the computed tomographic (CT) findings in
      immunocompetent patients with pulmonary cryptococcosis. MATERIALS AND METHODS:
      Institutional review board approval was obtained with a waiver of informed
      consent, and the study complied with requirements of the Health Insurance
      Portability and Accountability Act. Chest CT scans of 10 immunocompetent patients
      with clinically proved pulmonary cryptococcosis were retrospectively reviewed by
      four reviewers in consensus. Criterion for diagnosis of pulmonary cryptococcosis
      was (a) the histopathologic presence of the organism at lung biopsy or (b) a
      positive culture of a respiratory specimen or positive serum cryptococcal antigen
      test with clinical or radiographic evidence of active pulmonary infection.
      Patients included six women and four men ranging in age from 46 to 73 years
      (mean, 59 years). Scans were evaluated for nodules, masses, areas of ground-glass
      attenuation or of hazy increased attenuation, areas of consolidation, areas of
      cavitation, pleural effusions, linear opacities, septal thickening,
      lymphadenopathy, extent of parenchymal involvement, and distribution. RESULTS:
      The most common CT finding was pulmonary nodules (n = 9). Multiple nodules (n =
      7) were more common than solitary nodules (n = 2). Nodules most commonly occupied
      less than 10% of the pulmonary parenchyma (n = 7), measured less than 10 mm in
      diameter (n = 7), and had middle and upper lung predominance (n = 6). The
      majority of the nodules were well defined with smooth margins (n = 7). Multiple
      nodules were usually bilaterally distributed (n = 5). Masses (n = 2),
      lymphadenopathy (n = 2), areas of consolidation (n = 2), areas of hazy increased
      attenuation (n = 1), pleural effusion (n = 1), and areas of cavitation (n = 1)
      were uncommon. CONCLUSION: CT most commonly demonstrated pulmonary nodules in
      immunocompetent patients with pulmonary cryptococcosis. The nodules were most
      often multiple, small, well defined, and smoothly marginated with middle and
      upper lung predominance.

PMID- 15987985
TI  - Vascular brachytherapy with 192Ir after femoropopliteal stent implantation in
      high-risk patients: twelve-month follow-up results from the Vienna-5 trial.
AB  - PURPOSE: To prospectively evaluate the effectiveness of endovascular
      brachytherapy in the prevention of restenosis after femoropopliteal stent
      implantation in high-risk patients. MATERIALS AND METHODS: Patients provided
      written informed consent to participate in this study, which was approved by the
      ethics committee. A total of 88 patients (mean age, 67.7 years +/- 10.1; 57 men
      [65%], 31 women [35%]) with femoropopliteal lesions (mean treatment length, 16.8
      cm +/- 7.3) were included. Patients underwent percutaneous transluminal
      angioplasty (PTA) and stent implantation and were randomized in a double-blind
      fashion to undergo either gamma brachytherapy with an iridium 192 source or
      treatment with nonradioactive seeds. A 14-Gy dose of iridium 192 was prescribed
      at 2 mm into the arterial wall (target depth equals vessel radius plus 2 mm). The
      primary end point of the study was angiographic binary restenosis of more than
      50% at 6-month follow-up. Secondary end point was either percutaneous or surgical
      target lesion revascularization after 6 months. Continuous data are presented as
      mean +/- standard deviation. Categorical data are expressed as percentages.
      Student t test was used to compare continuous data; chi(2) test was used to
      compare categorical values. Survival function was calculated with the Kaplan
      Meier method. Multivariate Cox proportional hazard regression analysis was
      performed to enable evaluation of multivariate predictors of recurrence at 6- and
      12-month follow-up. Variables included brachytherapy, clinical stage, lesion
      length, de novo and recurrent lesion, vessel run off, prior stenosis or
      occlusion, diabetes mellitus, and stent model. RESULTS: Revascularization and
      brachytherapy were accomplished successfully in all patients. The overall 6-month
      recurrence rate was 35% in patients who underwent only stent implantation and 33%
      in patients who underwent both stent implantation and brachytherapy (P = .89).
      Nine (10%) patients developed early reocclusion in the segment treated with a
      stent (two patients [4%] in the stent group and seven [17%] in the stent and
      brachytherapy group); of these patients, three in the stent and brachytherapy
      group experienced reocclusion within 24 hours of the intervention. Late (>30 days
      after intervention) thrombotic occlusion was observed in three patients (7%) in
      the stent and brachytherapy group. CONCLUSION: Brachytherapy does not improve 6
      month patency after femoropopliteal stent implantation in high-risk patients
      because of a high incidence of early and late thrombotic occlusion.

PMID- 15987986
TI  - Comments on routine chest radiography.

PMID- 15987987
TI  - Test-bolus versus bolus-tracking techniques for CT angiographic timing.

PMID- 15987988
TI  - Osteonecrosis in the postoperative knee.

PMID- 15987989
TI  - Angiographic findings in patients with autoimmune pancreatitis.

PMID- 15987991
TI  - Promising new advances in head and neck radiotherapy.
AB  - Efforts to improve the efficacy of treatment for SCCHN have led to the use of
      multimodality approaches with combinations of surgery, radiotherapy and
      chemotherapy. Conventional head and neck radiotherapy, a standard approach for
      locoregionally advanced disease, is associated with a variety of well-known acute
      and long-term toxicities. These chronic toxicities (i.e. xerostomia, dysphagia,
      fibrosis) can impact negatively on patient quality of life. Altered radiation
      fractionation regimens that incorporate acceleration and/or hyperfractionation
      can improve locoregional control but also increase acute toxicities for head and
      neck cancer patients. Intensity modulated radiation therapy (IMRT) has emerged as
      a promising method for delivering effective radiation dose to head and neck
      tumour targets while reducing exposure of surrounding healthy tissue. Another
      method for improving head and neck cancer outcome with conventional radiotherapy
      is with the concurrent addition of chemotherapy. Indeed, chemoradiotherapy is now
      a standard treatment approach for locoregionally advanced disease. Molecular
      targeted agents, such as the epidermal growth factor receptor (EGFR) antagonist,
      cetuximab (Erbitux), have recently been shown to enhance the effects of
      radiotherapy, and reports to date suggest that this potentiation occurs without
      an increase in the characteristic toxicities associated with head and neck
      radiation.

PMID- 15987992
TI  - New approaches to enhance chemotherapy in SCCHN.
AB  - Chemotherapy is the standard approach to the treatment of patients with recurrent
      and metastatic squamous cell carcinoma of the head and neck (SCCHN) and is also
      now a common component of treatment for patients with locoregionally advanced,
      non-metastatic disease. Cisplatin has for many years been the agent of choice,
      alone or in combination with other agents, particularly 5-FU. The advent of the
      taxanes, which demonstrate good non-clinical activity against SCCHN, spawned a
      series of investigations aimed at integrating these agents into treatment
      regimens. Molecular targeted agents, which do not demonstrate overlapping
      toxicities with commonly used chemotherapy agents for SCCHN, represent a
      promising avenue of investigation. The epidermal growth factor receptor (EGFR) is
      expressed both widely and at high levels in SCCHN and is associated with poor
      prognosis. The EGFR-directed monoclonal antibody (MAb) cetuximab (Erbitux) in
      combination with chemotherapy has shown some activity in the treatment of
      recurrent/metastatic disease both as first-line therapy and following cisplatin
      failure, and preliminary results suggest single-agent activity in platinum
      resistant disease. Promising activity has also been observed with a number of
      other EGFR inhibitors, both MAbs and tyrosine kinase inhibitors.

PMID- 15987993
TI  - Current treatments and promising investigations in a multidisciplinary setting.
AB  - The care of the patient with squamous cell carcinoma of the head and neck (SCCHN)
      requires a multidisciplinary approach. For many years, radiotherapy following
      surgery was considered the standard approach to the treatment of locally advanced
      resectable disease. Data from randomized trials have confirmed the benefits of
      concurrent chemotherapy and radiotherapy (chemoradiotherapy) in this setting and
      this is now the gold standard for treatment. Chemoradiotherapy is also the
      recommended approach for unresectable disease. Neoadjuvant chemotherapy has been
      useful in resectable disease where organ preservation is desirable, but a
      concomitant approach is superior. Although survival benefits have not been
      consistently demonstrated, the theoretical potential of this approach has lead to
      continued investigations using newer agents, such as the taxanes. Novel targeted
      agents, such as antagonists of the epidermal growth factor receptor (EGFR), are
      showing promise in the treatment of patients with both locally advanced and
      recurrent/metastatic SCCHN. Treatment issues that require immediate attention
      include identifying optimal chemoradiotherapy regimens, clarifying the role of
      neoadjuvant chemotherapy, defining the optimal integration of targeted therapies
      into combined modality approaches and identifying useful prognostic and
      predictive factors.

PMID- 15987994
TI  - Redefining 'state of the art' in head and neck cancer.

PMID- 15987995
TI  - Current clinical outcomes demand new treatment options for SCCHN.
AB  - Head and neck cancer can be a devastating disease. The mainstays of treatment for
      early stage disease are either radiotherapy or surgery. However, although disease
      responds well at this stage, the risk of a second primary cancer is high, with a
      development rate of about 4% per year. Advanced diseases are treated either by
      surgery with postoperative radiotherapy or by definitive radiotherapy, with
      surgery in reserve for salvage if necessary. Over the past two decades major
      advances have been made in surgery (reconstructive surgery, non-mutilating
      surgery). Either definitive or postoperative, radiotherapy is an integral part of
      the treatment for the majority of non-metastatic stages of disease and ways of
      improving the effects of radiotherapy are constantly being explored. Good
      activity has been reported for the use of altered radiation fractionation
      regimens, which allow the delivery of intensified radiation doses. In addition,
      in recent years randomized trials and meta-analyses have confirmed the survival
      benefit of adding chemotherapy to radiotherapy in a number of different settings.
      Cisplatin-based regimens have been identified as the most active and are now
      standard treatment choices. The survival benefits of chemotherapy appear to be
      limited to concomitant administration and do not extend to neoadjuvant
      administration, although this has demonstrated clinical utility in preserving
      organ function. Platinum-based combination chemotherapy is by many clinicians
      considered the standard approach to the treatment of recurrent/metastatic disease
      for patients who are able to tolerate such regimens, but the prognosis for these
      patients remains poor; this is particularly true for those whose disease
      progresses on such therapy. This paper discusses current approaches and recent
      advances in the treatment of head and neck cancer, specifically squamous cell
      carcinoma, and suggests future management aims for the different disease stages.

PMID- 15987996
TI  - Redox homeostasis and antioxidant signaling: a metabolic interface between stress
      perception and physiological responses.

PMID- 15987997
TI  - Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a
      transforming target of Aurora-A.
AB  - Aurora-A, a mitotic serine/threonine kinase with oncogene characteristics, has
      recently drawn intense attention because of its association with the development
      of human cancers and its relationship with mitotic progression. Using the gene
      expression profiles of Aurora-A as a template to search for and compare
      transcriptome expression profiles in publicly accessible microarray data sets, we
      identified HURP (encodes hepatoma upregulated protein) as one of the best Aurora
      A-correlated genes. Empirical validation indicates that HURP has several
      characteristics in common with Aurora-A. These two genes have similar expression
      patterns in hepatocellular carcinoma, liver regeneration after partial
      hepatectomy, and cell cycle progression and across a variety of tissues and cell
      lines. Moreover, Aurora-A phosphorylated HURP in vitro and in vivo. Ectopic
      expression of either the catalytically inactive form of Aurora-A or the HURP-4P
      mutant, in which the Aurora-A phosphorylation sites were replaced with Ala,
      resulted in HURP instability and complex disassembly. In addition, HURP-wild-type
      stable transfectants were capable of growing in low-serum environments whereas
      HURP-4P grew poorly under low-serum conditions and failed to proliferate. These
      studies together support the view that the ability to integrate evidence derived
      from microarray studies into biochemical analyses may ultimately augment our
      predictive power when analyzing the potential role of poorly characterized
      proteins. While this combined approach was simply an initial attempt to answer a
      range of complex biological questions, our findings do suggest that HURP is a
      potential oncogenic target of Aurora-A.

PMID- 15987998
TI  - Involvement of human release factors eRF3a and eRF3b in translation termination
      and regulation of the termination complex formation.
AB  - eRF3 is a GTPase associated with eRF1 in a complex that mediates translation
      termination in eukaryotes. In mammals, two genes encode two distinct forms of
      eRF3, eRF3a and eRF3b, which differ in their N-terminal domains. Both bind eRF1
      and stimulate its release activity in vitro. However, whether both proteins can
      function as termination factors in vivo has not been determined. In this study,
      we used short interfering RNAs to examine the effect of eRF3a and eRF3b depletion
      on translation termination efficiency in human cells. By measuring the
      readthrough at a premature nonsense codon in a reporter mRNA, we found that eRF3a
      silencing induced an important increase in readthrough whereas eRF3b silencing
      had no significant effect. We also found that eRF3a depletion reduced the
      intracellular level of eRF1 protein by affecting its stability. In addition, we
      showed that eRF3b overexpression alleviated the effect of eRF3a silencing on
      readthrough and on eRF1 cellular levels. These results suggest that eRF3a is the
      major factor acting in translation termination in mammals and clearly demonstrate
      that eRF3b can substitute for eRF3a in this function. Finally, our data indicate
      that the expression level of eRF3a controls the formation of the termination
      complex by modulating eRF1 protein stability.

PMID- 15987999
TI  - The yeast FACT complex has a role in transcriptional initiation.
AB  - A crucial step in eukaryotic transcriptional initiation is recognition of the
      promoter TATA by the TATA-binding protein (TBP), which then allows TFIIA and
      TFIIB to be recruited. However, nucleosomes block the interaction between TBP and
      DNA. We show that the yeast FACT complex (yFACT) promotes TBP binding to a TATA
      box in chromatin both in vivo and in vitro. The SPT16 gene encodes a subunit of
      yFACT, and we show that certain spt16 mutations are synthetically lethal with TBP
      mutants. Some of these genetic defects can be suppressed by TFIIA overexpression,
      strongly suggesting a role for yFACT in TBP-TFIIA complex formation in vivo.
      Mutations in the TOA2 subunit of TFIIA that disrupt TBP-TFIIA complex formation
      in vitro are also synthetically lethal with spt16. In some cases this spt16 toa2
      lethality is suppressed by overexpression of TBP or the Nhp6 architectural
      transcription factor that is also a component of yFACT. The Spt3 protein in the
      SAGA complex has been shown to regulate TBP binding at certain promoters, and we
      show that some spt16 phenotypes can be suppressed by spt3 mutations. Chromatin
      immunoprecipitations show TBP binding to promoters is reduced in single spt16 and
      spt3 mutants but increases in the spt16 spt3 double mutant, reflecting the mutual
      suppression seen in the genetic assays. Finally, in vitro studies show that yFACT
      promotes TBP binding to a TATA sequence within a reconstituted nucleosome in a
      TFIIA-dependent manner. Thus, yFACT functions in establishing transcription
      initiation complexes in addition to the previously described role in elongation.

PMID- 15988000
TI  - Expression of a human cytochrome p450 in yeast permits analysis of pathways for
      response to and repair of aflatoxin-induced DNA damage.
AB  - Aflatoxin B1 (AFB1) is a human hepatotoxin and hepatocarcinogen produced by the
      mold Aspergillus flavus. In humans, AFB1 is primarily bioactivated by cytochrome
      P450 1A2 (CYP1A2) and 3A4 to a genotoxic epoxide that forms N7-guanine DNA
      adducts. A series of yeast haploid mutants defective in DNA repair and cell cycle
      checkpoints were transformed with human CYP1A2 to investigate how these DNA
      adducts are repaired. Cell survival and mutagenesis following aflatoxin B1
      treatment was assayed in strains defective in nucleotide excision repair (NER)
      (rad14), postreplication repair (PRR) (rad6, rad18, mms2, and rad5), homologous
      recombinational repair (HRR) (rad51 and rad54), base excision repair (BER) (apn1
      apn2), nonhomologous end-joining (NHEJ) (yku70), mismatch repair (MMR) (pms1),
      translesion synthesis (TLS) (rev3), and checkpoints (mec1-1, mec1-1 rad53, rad9,
      and rad17). Together our data suggest the involvement of homologous recombination
      and nucleotide excision repair, postreplication repair, and checkpoints in the
      repair and/or tolerance of AFB1-induced DNA damage in the yeast model. Rev3
      appears to mediate AFB1-induced mutagenesis when error-free pathways are
      compromised. The results further suggest unique roles for Rad5 and abasic
      endonuclease-dependent DNA intermediates in regulating AFB1-induced mutagenicity.

PMID- 15988001
TI  - Regulation of mTOR and cell growth in response to energy stress by REDD1.
AB  - The tuberous sclerosis tumor suppressors TSC1 and TSC2 regulate the mTOR pathway
      to control translation and cell growth in response to nutrient and growth factor
      stimuli. We have recently identified the stress response REDD1 gene as a mediator
      of tuberous sclerosis complex (TSC)-dependent mTOR regulation by hypoxia. Here,
      we demonstrate that REDD1 inhibits mTOR function to control cell growth in
      response to energy stress. Endogenous REDD1 is induced following energy stress,
      and REDD1-/- cells are highly defective in dephosphorylation of the key mTOR
      substrates S6K and 4E-BP1 following either ATP depletion or direct activation of
      the AMP-activated protein kinase (AMPK). REDD1 likely acts on the TSC1/2 complex,
      as regulation of mTOR substrate phosphorylation by REDD1 requires TSC2 and is
      blocked by overexpression of the TSC1/2 downstream target Rheb but is not blocked
      by inhibition of AMPK. Tetracycline-inducible expression of REDD1 triggers rapid
      dephosphorylation of S6K and 4E-BP1 and significantly decreases cellular size.
      Conversely, inhibition of endogenous REDD1 by short interfering RNA increases
      cell size in a rapamycin-sensitive manner, and REDD1-/- cells are defective in
      cell growth regulation following ATP depletion. These results define REDD1 as a
      critical transducer of the cellular response to energy depletion through the TSC
      mTOR pathway.

PMID- 15988002
TI  - GDF11 forms a bone morphogenetic protein 1-activated latent complex that can
      modulate nerve growth factor-induced differentiation of PC12 cells.
AB  - All transforming growth factor beta (TGF-beta) superfamily members are
      synthesized as precursors with prodomain sequences that are proteolytically
      removed by subtilisin-like proprotein convertases (SPCs). For most superfamily
      members, this is believed sufficient for activation. Exceptions are TGF-betas 1
      to 3 and growth differentiation factor 8 (GDF8), also known as myostatin, which
      form noncovalent, latent complexes with their SPC-cleaved prodomains. Sequence
      similarities between TGF-betas 1 to 3, myostatin, and superfamily member GDF11,
      also known as bone morphogenetic protein 11 (BMP11), prompted us to examine
      whether GDF11 might be capable of forming a latent complex with its cleaved
      prodomain. Here we demonstrate that GDF11 forms a noncovalent latent complex with
      its SPC-cleaved prodomain and that this latent complex is activated via cleavage
      at a single specific site by members of the developmentally important
      BMP1/Tolloid family of metalloproteinases. Evidence is provided for a molecular
      model whereby formation and activation of this complex may play a general role in
      modulating neural differentiation. In particular, mutant GDF11 prodomains
      impervious to cleavage by BMP1/Tolloid proteinases are shown to be potent
      stimulators of neurodifferentiation, with potential for therapeutic applications.

PMID- 15988003
TI  - c-Src-mediated phosphorylation of TRIP6 regulates its function in
      lysophosphatidic acid-induced cell migration.
AB  - TRIP6 (thyroid receptor-interacting protein 6), also known as ZRP-1 (zyxin
      related protein 1), is a member of the zyxin family that has been implicated in
      cell motility. Previously we have shown that TRIP6 binds to the LPA2 receptor and
      associates with several components of focal complexes in an agonist-dependent
      manner and, thus, enhances lysophosphatidic acid (LPA)-induced cell migration.
      Here we further report that the function of TRIP6 in LPA signaling is regulated
      by c-Src-mediated phosphorylation of TRIP6 at the Tyr-55 residue. LPA stimulation
      induces tyrosine phosphorylation of endogenous TRIP6 in NIH 3T3 cells and c-Src
      expressing fibroblasts, which is virtually eliminated in Src-null fibroblasts.
      Strikingly, both phosphotyrosine-55 and proline-58 residues of TRIP6 are required
      for Crk binding in vitro and in cells. Mutation of Tyr-55 to Phe does not alter
      the ability of TRIP6 to localize at focal adhesions or associate with actin.
      However, it abolishes the association of TRIP6 with Crk and p130cas in cells and
      significantly reduces the function of TRIP6 to promote LPA-induced ERK
      activation. Ultimately, these signaling events control TRIP6 function in
      promoting LPA-induced morphological changes and cell migration.

PMID- 15988005
TI  - A conserved Swi2/Snf2 ATPase motif couples ATP hydrolysis to chromatin
      remodeling.
AB  - Yeast (Saccharomyces cerevisiae) SWI/SNF is a prototype for a large family of ATP
      dependent chromatin-remodeling enzymes that facilitate numerous DNA-mediated
      processes. Swi2/Snf2 is the catalytic subunit of SWI/SNF, and it is the founding
      member of a novel subfamily of the SF2 superfamily of DNA helicase/ATPases. Here
      we present a functional analysis of the diagnostic set of helicase/ATPase
      sequence motifs found within all Swi2p/Snf2p family members. Whereas many of
      these motifs play key roles in ATP binding and/or hydrolysis, we identify
      residues within conserved motif V that are specifically required to couple ATP
      hydrolysis to chromatin-remodeling activity. Interestingly, motif V of the human
      Swi2p/Snf2p homolog, Brg1p, has been shown to be a possible hot spot for
      mutational alterations associated with cancers.

PMID- 15988004
TI  - Transcriptional repression of the Neurofibromatosis-1 tumor suppressor by the
      t(8;21) fusion protein.
AB  - Von Recklinghausen's disease is a relatively common familial genetic disorder
      characterized by inactivating mutations of the Neurofibromatosis-1 (NF1) gene
      that predisposes these patients to malignancies, including an increased risk for
      juvenile myelomonocytic leukemia. However, NF1 mutations are not common in acute
      myeloid leukemia (AML). Given that the RUNX1 transcription factor is the most
      common target for chromosomal translocations in acute leukemia, we asked if NF1
      might be regulated by RUNX1. In reporter assays, RUNX1 activated the NF1 promoter
      and cooperated with C/EBPalpha and ETS2 to activate the NF1 promoter over 80
      fold. Moreover, the t(8;21) fusion protein RUNX1-MTG8 (R/M), which represses
      RUNX1-regulated genes, actively repressed the NF1 promoter. R/M associated with
      the NF1 promoter in vivo and repressed endogenous NF1 gene expression. In
      addition, similar to loss of NF1, R/M expression enhanced the sensitivity of
      primary myeloid progenitor cells to granulocyte-macrophage colony-stimulating
      factor. Our results indicate that the NF1 tumor suppressor gene is a direct
      transcriptional target of RUNX1 and the t(8;21) fusion protein, suggesting that
      suppression of NF1 expression contributes to the molecular pathogenesis of AML.

PMID- 15988006
TI  - Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of
      MEF2 by NF-kappaB and histone deacetylases.
AB  - Activation of the endothelium by inflammatory cytokines is a key event in the
      pathogenesis of vascular disease states. Proinflammatory cytokines repress the
      expression of KLF2, a recently identified transcriptional inhibitor of the
      cytokine-mediated activation of endothelial cells. In this study the molecular
      basis for the cytokine-mediated inhibition of KLF2 is elucidated. Tumor necrosis
      factor alpha (TNF-alpha) potently inhibited KLF2 expression. This effect was
      completely abrogated by a constitutively active form of IkappaBalpha, as well as
      treatment with trichostatin A, implicating a role for the NF-kappaB pathway and
      histone deacetylases. Overexpression studies coupled with observations with
      p50/p65 null cells support an essential role for p65. A combination of promoter
      deletion and mutational analyses, chromatin immunoprecipitation assays, and co
      immunoprecipitation studies indicates that p65 and histone deacetylases 4
      cooperate to inhibit the ability of MEF2 factors to induce the KLF2 promoter.
      These studies identify a novel mechanism by which TNF-alpha can inhibit
      endothelial gene expression. Furthermore, the inhibition of MEF2 function by p65
      and HDAC4 has implications for other cellular systems where these factors are
      operative.

PMID- 15988007
TI  - Double-strand break formation by the RAG complex at the bcl-2 major breakpoint
      region and at other non-B DNA structures in vitro.
AB  - The most common chromosomal translocation in cancer, t(14;18) at the 150-bp bcl-2
      major breakpoint region (Mbr), occurs in follicular lymphomas. The bcl-2 Mbr
      assumes a non-B DNA conformation, thus explaining its distinctive fragility. This
      non-B DNA structure is a target of the RAG complex in vivo, but not because of
      its primary sequence. Here we report that the RAG complex generates at least two
      independent nicks that lead to double-strand breaks in vitro, and this requires
      the non-B DNA structure at the bcl-2 Mbr. A 3-bp mutation is capable of
      abolishing the non-B structure formation and the double-strand breaks. The
      observations on the bcl-2 Mbr reflect more general properties of the RAG complex,
      which can bind and nick at duplex-single-strand transitions of other non-B DNA
      structures, resulting in double-strand breaks in vitro. Hence, the present study
      reveals novel insight into a third mechanism of action of RAGs on DNA, besides
      the standard heptamer/nonamer-mediated cleavage in V(D)J recombination and the in
      vitro transposase activity.

PMID- 15988008
TI  - Sum1p, the origin recognition complex, and the spreading of a promoter-specific
      repressor in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, Sum1p is a promoter-specific repressor. A single
      amino acid change generates the mutant Sum1-1p, which causes regional silencing
      at new loci where wild-type Sum1p does not act. Thus, Sum1-1p is a model for
      understanding how the spreading of repressive chromatin is regulated. When wild
      type Sum1p was targeted to a locus where mutant Sum1-1p spreads, wild-type Sum1p
      did not spread as efficiently as mutant Sum1-1p did, despite being in the same
      genomic context. Thus, the SUM1-1 mutation altered the ability of the protein to
      spread. The spreading of Sum1-1p required both an enzymatically active
      deacetylase, Hst1p, and the N-terminal tail of histone H4, consistent with the
      spreading of Sum1-1p involving sequential modification of and binding to histone
      tails, as observed for other silencing proteins. Furthermore, deletion of the N
      terminal tail of H4 caused Sum1-1p to return to loci where wild-type Sum1p acts,
      consistent with the SUM1-1 mutation increasing the affinity of the protein for H4
      tails. These results imply that the spreading of repressive chromatin proteins is
      regulated by their affinities for histone tails. Finally, this study uncovered a
      functional connection between wild-type Sum1p and the origin recognition complex,
      and this relationship also contributes to mutant Sum1-1p localization.

PMID- 15988009
TI  - Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit
      transcription indirectly via NF-kappaB and AP-1.
AB  - Glutamate-cysteine ligase catalytic subunit (GCLC) is regulated transcriptionally
      by Nrf1 and Nrf2. tert-Butylhydroquinone (TBH) induces human GCLC via Nrf2
      mediated trans activation of the antioxidant-responsive element (ARE).
      Interestingly, TBH also induces rat GCLC, but the rat GCLC promoter lacks ARE.
      This study examined the role of Nrf1 and Nrf2 in the transcriptional regulation
      of rat GCLC. The baseline and TBH-mediated increase in GCLC mRNA levels and rat
      GCLC promoter activity were lower in Nrf1 and Nrf2 null (F1 and F2) fibroblasts
      than in wild-type cells. The basal protein and mRNA levels and nuclear binding
      activities of c-Jun, c-Fos, p50, and p65 were lower in F1 and F2 cells and
      exhibited a blunted response to TBH. Lower c-Jun and p65 expression also occurs
      in Nrf2 null livers. Levels of other AP-1 and NF-kappaB family members were
      either unaffected (i.e., JunB) or increased (i.e., Fra-1). Overexpression of Nrf1
      and Nrf2 in respective cells restored the rat GCLC promoter activity and response
      to TBH but not if the AP-1 and NF-kappaB binding sites were mutated. Fra-1
      overexpression lowered endogenous GCLC expression and rat GCLC promoter activity,
      while Fra-1 antisense had the opposite effects. In conclusion, Nrf1 and Nrf2
      regulate rat GCLC promoter by modulating the expression of key AP-1 and NF-kappaB
      family members.

PMID- 15988010
TI  - The MRG domain mediates the functional integration of MSL3 into the dosage
      compensation complex.
AB  - The male-specific-lethal (MSL) proteins in Drosophila melanogaster serve to
      adjust gene expression levels in male flies containing a single X chromosome to
      equal those in females with a double dose of X-linked genes. Together with
      noncoding roX RNA, MSL proteins form the "dosage compensation complex" (DCC),
      which interacts selectively with the X chromosome to restrict the transcription
      activating histone H4 acetyltransferase MOF (males-absent-on-the-first) to that
      chromosome. We showed previously that MSL3 is essential for the activation of
      MOF's nucleosomal histone acetyltransferase activity within an MSL1-MOF complex.
      By characterizing the MSL3 domain structure and its associated functions, we now
      found that the nucleic acid binding determinants reside in the N terminus of
      MSL3, well separable from the C-terminal MRG signatures that form an integrated
      domain required for MSL1 interaction. Interaction with MSL1 mediates the
      activation of MOF in vitro and the targeting of MSL3 to the X-chromosomal
      territory in vivo. An N-terminal truncation that lacks the chromo-related domain
      and all nucleic acid binding activity is able to trigger de novo assembly of the
      DCC and establishment of an acetylated X-chromosome territory.

PMID- 15988011
TI  - Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation.
AB  - Mitogen-activated protein kinase (MAPK) cascades are central components of the
      intracellular signaling networks used by eukaryotic cells to respond to a wide
      spectrum of extracellular stimuli. An MAPK is activated by an MAPK kinase, which
      in turn is activated by an MAPK kinase kinase (MAP3K). However, little is known
      about the molecular aspects of the regulation and activation of large numbers of
      MAP3Ks that are crucial in relaying upstream receptor-mediated signals through
      the MAPK cascades to induce various physiological responses. In this study, we
      identified a novel MEKK2-interacting protein, Mip1, that regulates MEKK2
      dimerization and activation by forming a complex with inactive and
      nonphosphorylated MEKK2. In particular, Mip1 prevented MEKK2 activation by
      blocking MEKK2 dimer formation, which in turn blocked JNKK2, c-Jun N-terminal
      kinase 1 (JNK1), extracellular signal-regulated kinase 5, and AP-1 reporter gene
      activation by MEKK2. Furthermore, we found that the endogenous Mip1-MEKK2 complex
      was dissociated transiently following epidermal growth factor stimulation. In
      contrast, the knockdown of Mip1 expression by siRNA augmented the MEKK2-mediated
      JNK and AP-1 reporter activation. Together, our data suggest a novel model for
      MEKK2 regulation and activation.

PMID- 15988012
TI  - GAC63, a GRIP1-dependent nuclear receptor coactivator.
AB  - Nuclear receptors (NRs) regulate target gene transcription through the
      recruitment of multiple coactivator complexes to the promoter regions of target
      genes. One important coactivator complex includes a p160 coactivator (GRIP1, SRC
      1, or ACTR) and its downstream coactivators (e.g., p300, CARM1, CoCoA, and Fli
      I), which contribute to transcriptional activation by protein acetylation,
      protein methylation, and protein-protein interactions. In this study, we
      identified a novel NR coactivator, GAC63, which binds to the N-terminal region of
      p160 coactivators as well as the ligand binding domains of some NRs. GAC63
      enhanced transcriptional activation by NRs in a hormone-dependent and GRIP1
      dependent manner in transient transfection assays and cooperated synergistically
      and selectively with other NR coactivators, including GRIP1 and CARM1, to enhance
      estrogen receptor function. Endogenous GAC63 was recruited to the estrogen
      responsive pS2 gene promoter of MCF-7 cells in response to the hormone. Reduction
      of the endogenous GAC63 level by small interfering RNA inhibited transcriptional
      activation by the hormone-activated estrogen receptor. Thus, GAC63 is a
      physiologically relevant part of the p160 coactivator signaling pathway that
      mediates transcriptional activation by NRs.

PMID- 15988013
TI  - Aberrant morphology and residual transmitter release at the Munc13-deficient
      mouse neuromuscular synapse.
AB  - In cultured hippocampal neurons, synaptogenesis is largely independent of
      synaptic transmission, while several accounts in the literature indicate that
      synaptogenesis at cholinergic neuromuscular junctions in mammals appears to
      partially depend on synaptic activity. To systematically examine the role of
      synaptic activity in synaptogenesis at the neuromuscular junction, we
      investigated neuromuscular synaptogenesis and neurotransmitter release of mice
      lacking all synaptic vesicle priming proteins of the Munc13 family. Munc13
      deficient mice are completely paralyzed at birth and die immediately, but form
      specialized neuromuscular endplates that display typical synaptic features.
      However, the distribution, number, size, and shape of these synapses, as well as
      the number of motor neurons they originate from and the maturation state of
      muscle cells, are profoundly altered. Surprisingly, Munc13-deficient synapses
      exhibit significantly increased spontaneous quantal acetylcholine release,
      although fewer fusion-competent synaptic vesicles are present and nerve
      stimulation-evoked secretion is hardly elicitable and strongly reduced in
      magnitude. We conclude that the residual transmitter release in Munc13-deficient
      mice is not sufficient to sustain normal synaptogenesis at the neuromuscular
      junction, essentially causing morphological aberrations that are also seen upon
      total blockade of neuromuscular transmission in other genetic models. Our data
      confirm the importance of Munc13 proteins in synaptic vesicle priming at the
      neuromuscular junction but indicate also that priming at this synapse may differ
      from priming at glutamatergic and gamma-aminobutyric acid-ergic synapses and is
      partly Munc13 independent. Thus, non-Munc13 priming proteins exist at this
      synapse or vesicle priming occurs in part spontaneously: i.e., without dedicated
      priming proteins in the release machinery.

PMID- 15988014
TI  - Nucleolar sequestration of RelA (p65) regulates NF-kappaB-driven transcription
      and apoptosis.
AB  - The molecular mechanisms that regulate nuclear NF-kappaB to determine whether the
      stimulation of this pathway has a pro- or anti-apoptotic effect on cells have yet
      to be fully defined. Nuclear compartmentalization is increasingly recognized as
      an important mechanism for regulating the activity of transcription-related
      proteins and modulating cell growth and death. We have investigated whether such
      compartmentalization serves as a mechanism for regulating NF-kappaB
      transcriptional activity. We demonstrate that the RelA component of NF-kappaB is
      sequestered in the nucleolus in response to the proapoptotic NF-kappaB stimuli
      aspirin, serum withdrawal, and UV-C radiation. In contrast, RelA is excluded from
      the nucleolus in response to the cytokines tumor necrosis factor and TRAIL. We
      identify an N-terminal motif of RelA that is essential for the nucleolar
      localization of the protein and show that deleting this motif inhibits the
      translocation of RelA from the nucleoplasm to the nucleolus. We demonstrate that
      the nucleolar accumulation of RelA is paralleled by a decrease in basal levels of
      NF-kappaB transcriptional activity and by apoptosis. Furthermore, we show that
      the retention of RelA in the nucleoplasm inhibits this decrease in NF-kappaB
      driven transcription and blocks apoptosis induced by aspirin and UV-C radiation.
      This work identifies a novel cellular mechanism for regulating NF-kappaB-driven
      transcription and apoptosis, involving the nucleolar sequestration of a key NF
      kappaB subunit. These data contribute to the understanding of the complexities of
      NF-kappaB function and have considerable relevance to cancer prevention and
      therapy.

PMID- 15988015
TI  - Erythroid cell-specific alpha-globin gene regulation by the CP2 transcription
      factor family.
AB  - We previously demonstrated that ubiquitously expressed CP2c exerts potent
      erythroid-specific transactivation of alpha-globin through an unknown mechanism.
      This mechanism is reported here to involve specific CP2 splice variants and
      protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice
      isoform of CP2, CP2b, which is identical to CP2a except that it has an additional
      36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific
      transcriptional activation domain, which requires the extra exon and can form
      heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity
      found in CP2a and CP2c. Transcriptional activation of alpha-globin occurred
      following dimerization between CP2b and CP2c in erythroid K562 and MEL cells, but
      this dimerization did not activate the alpha-globin promoter in nonerythroid 293T
      cells, indicating that an additional erythroid factor is missing in 293T cells.
      PIAS1 was confirmed as a CP2 binding protein by the yeast two-hybrid screen, and
      expression of CP2b, CP2c, and PIAS1 in 293T cell induced alpha-globin promoter
      activation. These results show that ubiquitously expressed CP2b exerts potent
      erythroid cell-specific alpha-globin gene expression by complexing with CP2c and
      PIAS1.

PMID- 15988016
TI  - Sites that direct nuclear compartmentalization are near the 5' end of the mouse
      immunoglobulin heavy-chain locus.
AB  - VDJ rearrangement in the mouse immunoglobulin heavy chain (Igh) locus involves a
      combination of events, including a large change in its nuclear
      compartmentalization. Prior to rearrangement, Igh moves from its default
      peripheral location near the nuclear envelope to an interior compartment, and
      after rearrangement it returns to the periphery. To identify any sites in Igh
      responsible for its association with the periphery, we systematically analyzed
      the nuclear positions of the Igh locus in mouse non-B- and B-cell lines and,
      importantly, in primary splenic lipopolysaccharide-stimulated B cells and
      plasmablasts. We found that a broad approximately 1-Mb region in the 5' half of
      the variable-gene region heavy-chain (Vh) locus regularly colocalizes with the
      nuclear lamina. The 3' half of the Vh gene region is less frequently colocalized
      with the periphery, while sequences flanking the Vh gene region are infrequently
      so. Importantly, in plasmacytomas, VDJ rearrangements that delete most of the Vh
      locus, including part of the 5' half of the Vh gene region, result in loss of
      peripheral compartmentalization, while deletion of only the proximal half of the
      Vh gene region does not. In addition, when Igh-Myc translocations move the Vh
      genes to a new chromosome, the distal Vh gene region is still associated with the
      nuclear periphery. Thus, the Igh region that interacts with the nuclear periphery
      is localized but is likely comprised of multiple sites that are distributed over
      approximately 1 Mb in the 5' half of the Vh gene region. This 5' Vh gene region
      that produces peripheral compartmentalization is the same region that is
      distinguished by requirements for interleukin-7, Pax5, and Ezh2 for rearrangement
      of the Vh genes.

PMID- 15988017
TI  - Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2
      complex in embryonic stem cells.
AB  - Embryonic stem cells (ESCs) are pluripotent cells that can either self-renew or
      differentiate into many cell types. Oct4 and Sox2 are transcription factors
      essential to the pluripotent and self-renewing phenotypes of ESCs. Both factors
      are upstream in the hierarchy of the transcription regulatory network and are
      partners in regulating several ESC-specific genes. In ESCs, Sox2 is
      transcriptionally regulated by an enhancer containing a composite sox-oct element
      that Oct4 and Sox2 bind in a combinatorial interaction. It has previously been
      shown that Pou5f1, the Oct4 gene, contains a distal enhancer imparting specific
      expression in both ESCs and preimplantation embryos. Here, we identify a
      composite sox-oct element within this enhancer and show that it is involved in
      Pou5f1 transcriptional activity in ESCs. In vitro experiments with ESC nuclear
      extracts demonstrate that Oct4 and Sox2 interact specifically with this
      regulatory element. More importantly, by chromatin immunoprecipitation assay, we
      establish that both Oct4 and Sox2 bind directly to the composite sox-oct elements
      in both Pou5f1 and Sox2 in living mouse and human ESCs. Specific knockdown of
      either Oct4 or Sox2 by RNA interference leads to the reduction of both genes'
      enhancer activities and endogenous expression levels in addition to ESC
      differentiation. Our data uncover a positive and potentially self-reinforcing
      regulatory loop that maintains Pou5f1 and Sox2 expression via the Oct4/Sox2
      complex in pluripotent cells.

PMID- 15988018
TI  - Activation of a nuclear Cdc2-related kinase within a mitogen-activated protein
      kinase-like TDY motif by autophosphorylation and cyclin-dependent protein kinase
      activating kinase.
AB  - Male germ cell-associated kinase (MAK) and intestinal cell kinase (ICK) are
      nuclear Cdc2-related kinases with nearly identical N-terminal catalytic domains
      and more divergent C-terminal noncatalytic domains. The catalytic domain is also
      related to mitogen-activated protein kinases (MAPKs) and contains a corresponding
      TDY motif. Nuclear localization of ICK requires subdomain XI and interactions of
      the conserved Arg-272, but not kinase activity or, surprisingly, any of the
      noncatalytic domain. Further, nuclear localization of ICK is required for its
      activation. ICK is activated by dual phosphorylation of the TDY motif.
      Phosphorylation of Tyr-159 in the TDY motif requires ICK autokinase activity but
      confers only basal kinase activity. Full activation requires additional
      phosphorylation of Thr-157 in the TDY motif. Coexpression of ICK with
      constitutively active MEK1 or MEK5 fails to increase ICK phosphorylation or
      activity, suggesting that MEKs are not involved. ICK and MAK are related to Ime2p
      in budding yeast, and cyclin-dependent protein kinase-activating kinase Cak1p has
      been placed genetically upstream of Ime2p. Recombinant Cak1p phosphorylates Thr
      157 in the TDY motif of recombinant ICK and activates its activity in vitro.
      Coexpression of ICK with wild-type CAK1 but not kinase-inactive CAK1 in cells
      also increases ICK phosphorylation and activity. Our studies establish ICK as the
      prototype for a new group of MAPK-like kinases requiring dual phosphorylation at
      TDY motifs.

PMID- 15988019
TI  - Dysregulation of the peroxisome proliferator-activated receptor target genes by
      XPD mutations.
AB  - Mutations in the XPD subunit of TFIIH give rise to human genetic disorders
      initially defined as DNA repair syndromes. Nevertheless, xeroderma pigmentosum
      (XP) group D (XP-D) patients develop clinical features such as hypoplasia of the
      adipose tissue, implying a putative transcriptional defect. Knowing that
      peroxisome proliferator-activated receptors (PPARs) are implicated in lipid
      metabolism, we investigated the expression of PPAR target genes in the adipose
      tissues and the livers of XPD-deficient mice and found that (i) some genes are
      abnormally overexpressed in a ligand-independent manner which parallels an
      increase in the recruitment of RNA polymerase (pol) II but not PPARs on their
      promoter and (ii) upon treatment with PPAR ligands, other genes are much less
      induced compared to the wild type, which is due to a lower recruitment of both
      PPARs and RNA pol II. The defect in transactivation by PPARs is likely
      attributable to their weaker phosphorylation by the cdk7 kinase of TFIIH. Having
      identified the phosphorylated residues in PPAR isotypes, we demonstrate how their
      transactivation defect in XPD-deficient cells can be circumvented by
      overexpression of either a wild-type XPD or a constitutively phosphorylated PPAR
      S/E. This work emphasizes that underphosphorylation of PPARs affects their
      transactivation and consequently the expression of PPAR target genes, thus
      contributing in part to the XP-D phenotype.

PMID- 15988020
TI  - Differential recognition of response elements determines target gene specificity
      for p53 and p63.
AB  - p63 is a member of the p53 tumor suppressor gene family, which regulates
      downstream target gene expression by binding to sequence-specific response
      elements similar to those of p53. By using oligonucleotide expression microarray
      analysis and analyzing the promoters of p63-induced genes, we have identified
      novel p63-specific response elements (p63-REs) in the promoter regions of EVPL
      and SMARCD3. These p63-REs exhibit characteristic differences from the canonical
      p53-RE (RRRCWWGYYY) in both the core-binding element (CWWG) as well as the RRR
      and/or YYY stretches. Luciferase assays on mutagenized promoter constructs
      followed by electromobility shift analysis showed that p53 preferentially
      activates and binds to the RRRCATGYYY sequence, whereas p63 preferentially
      activates RRRCGTGYYY. Whereas EVPL protein is highly expressed in epithelial
      cells of the skin and pharynx in the p63+/+ mouse, it is undetectable in these
      tissues in the p63-/- mouse. Our results indicate that p63 can regulate
      expression of specific target genes such as those involved in skin, limb, and
      craniofacial development by preferentially activating distinct p63-specific
      response elements.

PMID- 15988021
TI  - Targeted deletion of the integrin beta4 signaling domain suppresses laminin-5
      dependent nuclear entry of mitogen-activated protein kinases and NF-kappaB,
      causing defects in epidermal growth and migration.
AB  - The alpha6beta4 integrin-a laminin-5 receptor-mediates assembly of hemidesmosomes
      and recruitment of Shc and phosphoinositide 3-kinase through the unique
      cytoplasmic extension of beta4. Mice carrying a targeted deletion of the
      signaling domain of beta4 develop normally and do not display signs of skin
      fragility. The epidermis of these mice contains well-structured hemidesmosomes
      and adheres stably to the basement membrane. However, it is hypoplastic due to
      reduced proliferation of basal keratinocytes and undergoes wound repair at a
      reduced rate. Keratinocytes from beta4 mutant mice undergo extensive spreading
      but fail to proliferate and migrate in response to epidermal growth factor (EGF)
      on laminin-5. EGF causes significant phosphorylation of extracellular signal
      regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) and
      phosphorylation and degradation of IkappaB in beta4 mutant cells adhering to
      laminin-5. Unexpectedly, however, ERK, JNK, and NF-kappaB remain in the cytoplasm
      in beta4 mutant cells on laminin-5, whereas they enter effectively into the
      nucleus in the same cells on fibronectin or in wild-type cells on both matrix
      proteins. Inhibitor studies indicate that alpha6beta4 promotes keratinocyte
      proliferation and migration through its effect on NF-kappaB and P-JNK. These
      findings provide evidence that beta4 signaling promotes epidermal growth and
      wound healing through a previously unrecognized effect on nuclear translocation
      of NF-kappaB and mitogen-activated protein kinases.

PMID- 15988022
TI  - Multiple roles of vertebrate REV genes in DNA repair and recombination.
AB  - In yeast, Rev1, Rev3, and Rev7 are involved in translesion synthesis over various
      kinds of DNA damage and spontaneous and UV-induced mutagenesis. Here, we
      disrupted Rev1, Rev3, and Rev7 in the chicken B-lymphocyte line DT40. REV1-/-
      REV3-/- REV7-/- cells showed spontaneous cell death, chromosomal
      instability/fragility, and hypersensitivity to various genotoxic treatments as
      observed in each of the single mutants. Surprisingly, the triple-knockout cells
      showed a suppressed level of sister chromatid exchanges (SCEs), which may reflect
      postreplication repair events mediated by homologous recombination, while each
      single mutant showed an elevated SCE level. Furthermore, REV1-/- cells as well as
      triple mutants showed a decreased level of immunoglobulin gene conversion,
      suggesting participation of Rev1 in a recombination-based pathway. The present
      study gives us a new insight into cooperative function of three Rev molecules and
      the Polzeta (Rev3-Rev7)-independent role of Rev1 in vertebrate cells.

PMID- 15988023
TI  - Structural dynamics of alpha-actinin-vinculin interactions.
AB  - Alpha-actinin and vinculin orchestrate reorganization of the actin cytoskeleton
      following the formation of adhesion junctions. alpha-Actinin interacts with
      vinculin through the binding of an alpha-helix (alphaVBS) present within the R4
      spectrin repeat of its central rod domain to vinculin's N-terminal seven-helical
      bundle domain (Vh1). The Vh1:alphaVBS structure suggests that alphaVBS first
      unravels from its buried location in the triple-helical R4 repeat to allow it to
      bind to vinculin. alphaVBS binding then induces novel conformational changes in
      the N-terminal helical bundle of Vh1, which disrupt its intramolecular
      association with vinculin's tail domain and which differ from the alterations in
      Vh1 provoked by the binding of talin. Surprisingly, alphaVBS binds to Vh1 in an
      inverted orientation compared to the binding of talin's VBSs to vinculin.
      Importantly, the binding of alphaVBS and talin's VBSs to vinculin's Vh1 domain
      appear to also trigger distinct conformational changes in full-length vinculin,
      opening up distant regions that are buried in the inactive molecule. The data
      suggest a model where vinculin's Vh1 domain acts as a molecular switch that
      undergoes distinct structural changes provoked by talin and alpha-actinin binding
      in focal adhesions versus adherens junctions, respectively.

PMID- 15988024
TI  - Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B: distinct
      roles in telomeric silencing and general chromatin.
AB  - We previously discovered that the ubiquitin protease Ubp10/Dot4p is important for
      telomeric silencing through its interaction with Sir4p. However, the mechanism of
      Ubp10p action was unknown. We now provide evidence that Ubp10p removes ubiquitin
      from histone H2B; cells with UBP10 deleted have increased steady-state levels of
      H2B ubiquitination. As a consequence, ubp10delta cells also have increased steady
      state levels of histone H3 Lys4 and Lys79 methylation. Consistent with its role
      in silencing, Ubp10p is preferentially localized to silent chromatin where its
      ubiquitin protease activity maintains low levels of H3 Lys4 and Lys79 methylation
      to allow optimal Sir protein binding to telomeres and global telomeric silencing.
      The ubiquitin protease Ubp8p has also been shown to remove ubiquitin from H2B,
      and ubp8delta cells have increased steady-state levels of H2B ubiquitination
      similar to those in ubp10delta cells. Unlike ubp10delta cells, however, ubp8delta
      cells do not have increased steady-state levels of H3 Lys4 and Lys79 methylation,
      nor is telomeric silencing affected. Despite their separate functions in
      silencing and SAGA-mediated transcription, respectively, deletion of both UBP10
      and UBP8 results in a synergistic increase in the steady-state levels of H2B
      ubiquitination and in the number of genes with altered expression, indicating
      that Ubp10p and Ubp8p likely overlap in some of their target chromatin regions.
      We propose that Ubp10p and Ubp8p are the only ubiquitin proteases that normally
      remove monoubiquitin from histone H2B and, while there are regions of the genome
      to which each is specifically targeted, both combine to regulate the global
      balance of H2B ubiquitination.

PMID- 15988025
TI  - HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene
      regulation at the G1/S phase cell cycle transition.
AB  - Genome replication in eukaryotic cells necessitates the stringent coupling of
      histone biosynthesis with the onset of DNA replication at the G1/S phase
      transition. A fundamental question is the mechanism that links the restriction
      (R) point late in G1 with histone gene expression at the onset of S phase. Here
      we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent
      histone H4 genes, interacts directly with p220(NPAT), a substrate of cyclin
      E/CDK2, to coactivate histone genes during S phase. HiNF-P and p220 are targeted
      to, and colocalize at, subnuclear foci (Cajal bodies) in a cell cycle-dependent
      manner. Genetic or biochemical disruption of the HiNF-P/p220 interaction
      compromises histone H4 gene activation at the G1/S phase transition and impedes
      cell cycle progression. Our results show that HiNF-P and p220 form a critical
      regulatory module that directly links histone H4 gene expression at the G1/S
      phase transition to the cyclin E/CDK2 signaling pathway at the R point.

PMID- 15988026
TI  - DNA-binding and transactivation activities are essential for TAp63 protein
      degradation.
AB  - The p53-related p63 gene encodes six isoforms with differing N and C termini.
      TAp63 isoforms possess a transactivation domain at the N terminus and are able to
      transactivate a set of genes, including some targets downstream of p53.
      Accumulating evidence indicates that TAp63 plays an important role in regulation
      of cell proliferation, differentiation, and apoptosis, whereas transactivation
      inert deltaNp63 functions to inhibit p63 and other p53 family members. Mutations
      in the p63 gene that abolish p63 DNA-binding and transactivation activities cause
      human diseases, including ectrodactyly ectodermal dysplasia and facial clefting
      (EEC) syndrome. In this study, we show that mutant p63 proteins with a single
      amino acid substitution found in EEC syndrome are DNA binding deficient,
      transactivation inert, and highly stable. We demonstrate that TAp63 protein
      expression is tightly controlled by its specific DNA-binding and transactivation
      activities and that p63 is degraded in a proteasome-dependent, MDM2-independent
      pathway. In addition, the N-terminal transactivation domain of p63 is
      indispensable for its protein degradation. Furthermore, the wild-type TAp63gamma
      can act in trans to promote degradation of mutant TAp63gamma defective in DNA
      binding, and the TA domain deletion mutant of TAp63gamma inhibits transactivation
      activity and stabilizes the wild-type TAp63 protein. Taken together, these data
      suggest a feedback loop for p63 regulation, analogous to the p53-MDM2 feedback
      loop.

PMID- 15988027
TI  - Replacement by Drosophila melanogaster protamines and Mst77F of histones during
      chromatin condensation in late spermatids and role of sesame in the removal of
      these proteins from the male pronucleus.
AB  - Chromatin condensation is a typical feature of sperm cells. During mammalian
      spermiogenesis, histones are first replaced by transition proteins and then by
      protamines, while little is known for Drosophila melanogaster. Here we
      characterize three genes in the fly genome, Mst35Ba, Mst35Bb, and Mst77F. The
      results indicate that Mst35Ba and Mst35Bb encode dProtA and dProtB, respectively.
      These are considerably larger than mammalian protamines, but, as in mammals, both
      protamines contain typical cysteine/arginine clusters. Mst77F encodes a linker
      histone-like protein showing significant similarity to mammalian HILS1 protein.
      ProtamineA-enhanced green fluorescent protein (eGFP), ProtamineB-eGFP, and Mst77F
      eGFP carrying Drosophila lines show that these proteins become the important
      chromosomal protein components of elongating spermatids, and His2AvDGFP vanishes.
      Mst77F mutants [ms(3)nc3] are characterized by small round nuclei and are sterile
      as males. These data suggest the major features of chromatin condensation in
      Drosophila spermatogenesis correspond to those in mammals. During early
      fertilization steps, the paternal pronucleus still contains protamines and Mst77F
      but regains a nucleosomal conformation before zygote formation. In eggs laid by
      sesame-deficient females, the paternal pronucleus remains in a protamine-based
      chromatin status but Mst77F-eGFP is removed, suggesting that the sesame gene
      product is essential for removal of protamines while Mst77F removal is
      independent of Sesame.

PMID- 15988029
TI  - Loss of histochemical identity in mast cells lacking carboxypeptidase A.
AB  - Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule
      protease. The onset of expression in mast cell progenitors and lineage
      specificity suggest an important role for Mc-cpa in mast cells. To address the
      function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa-/- mast cells lacked
      carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While
      Mc-cpa-/- peritoneal mast cells were ultrastructurally normal and synthesized
      normal amounts of heparin, they displayed striking histochemical and biochemical
      hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature
      phenotype characterized by differential histochemical staining with proteoglycan
      reactive dyes (cells do not stain with alcian blue but stain with safranin and
      with berberine) and a high side scatter to forward scatter ratio by flow
      cytometry and were detergent resistant. In contrast, Mc-cpa-/- peritoneal mast
      cells, like immature bone marrow-derived cultured mast cells, stained with alcian
      blue normally or weakly and either did not stain with safranin and berberine or
      stained weakly, had a low side scatter to forward scatter ratio, and were
      detergent sensitive. This phenotype was partially ameliorated with age. Thus,
      histochemistry and flow cytometry, commonly used to measure mast cell maturation,
      deviated from morphology in Mc-cpa-/- mice. The Mc-cpa-/- mast cell phenotype was
      not associated with defects in degranulation in vitro or passive cutaneous
      anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation
      of phenotypically mature mast cells.

PMID- 15988028
TI  - A human T-cell lymphotropic virus type 1 enhancer of Myc transforming potential
      stabilizes Myc-TIP60 transcriptional interactions.
AB  - The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4+
      lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive
      lymphoproliferative disease that is often fatal. Here, we demonstrate that the
      HTLV-1 pX splice-variant p30II markedly enhances the transforming potential of
      Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon
      its conserved Myc-responsive E-box enhancer elements, which are associated with
      increased S-phase entry and multinucleation. Enhancement of c-Myc transforming
      activity by HTLV-1 p30II is dependent upon the transcriptional coactivators,
      transforming transcriptional activator protein/p434 and TIP60, and it requires
      TIP60 histone acetyltransferase (HAT) activity and correlates with the
      stabilization of HTLV-1 p30II/Myc-TIP60 chromatin-remodeling complexes. The p30II
      oncoprotein colocalizes and coimmunoprecipitates with Myc-TIP60 complexes in
      cultured HTLV-1-infected ATLL patient lymphocytes. Amino acid residues 99 to 154
      within HTLV-1 p30II interact with the TIP60 HAT, and p30II transcriptionally
      activates numerous cellular genes in a TIP60-dependent or TIP60-independent
      manner, as determined by microarray gene expression analyses. Importantly, these
      results suggest that p30II functions as a novel retroviral modulator of Myc-TIP60
      transforming interactions that may contribute to adult T-cell leukemogenesis.

PMID- 15988030
TI  - Nuclear PTEN-mediated growth suppression is independent of Akt down-regulation.
AB  - The tumor suppressor gene PTEN is a phosphoinositide phosphatase that is
      inactivated by deletion and/or mutation in diverse human tumors. Wild-type PTEN
      is expressed both in the cytoplasm and nucleus in normal cells, with a
      preferential nuclear localization in differentiated or resting cells. To
      elucidate the relationship between PTEN's subcellular localization and its
      biologic activities, we constructed different PTEN mutants that targeted PTEN
      protein into different subcellular compartments. Our data show that the
      subcellular localization patterns of a PTEN (deltaPDZB) mutant versus a G129R
      phosphatase mutant were indistinguishable from those of wild-type PTEN. In
      contrast, the Myr-PTEN mutant demonstrated an enhanced association with the cell
      membrane. We found that nuclear PTEN alone is capable of suppressing anchorage
      independent growth and facilitating G1 arrest in U251MG cells without inhibiting
      Akt activity. Nuclear compartment-specific PTEN-induced growth suppression is
      dependent on possessing a functional lipid phosphatase domain. In addition, the
      down-regulation of p70S6K could be mediated, at least in part, through activation
      of AMP-activated protein kinase in an Akt-independent fashion. Introduction of a
      constitutively active mutant of Akt, Akt-DD, only partially rescues nuclear PTEN
      mediated growth suppression. Our collective results provide the first direct
      evidence that PTEN can contribute to G1 growth arrest through an Akt-independent
      signaling pathway.

PMID- 15988031
TI  - Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial
      biogenesis.
AB  - Although several genes involved in mitochondrial function are direct Myc targets,
      the role of Myc in mitochondrial biogenesis has not been directly established. We
      determined the effects of ectopic Myc expression or the loss of Myc on
      mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased
      oxygen consumption and mitochondrial mass and function. Conversely, compared to
      wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial
      mass and decreased number of normal mitochondria. Reconstitution of Myc
      expression in Myc null fibroblasts partially restored mitochondrial mass and
      function and normal-appearing mitochondria. Concordantly, we also observed in
      primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase
      resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray
      analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role
      for Myc in mitochondrial biogenesis, since genes involved in mitochondrial
      structure and function are overrepresented among the Myc-induced genes. In
      addition to the known direct binding of Myc to many genes involved in
      mitochondrial structure and function, we found that Myc binds the TFAM gene,
      which encodes a key transcriptional regulator and mitochondrial DNA replication
      factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum
      stimulated primary human 2091 fibroblasts with induced endogenous MYC. These
      observations support a pivotal role for Myc in regulating mitochondrial
      biogenesis.

PMID- 15988032
TI  - The oncogenic TLS-ERG fusion protein exerts different effects in hematopoietic
      cells and fibroblasts.
AB  - The oncogenic TLS-ERG fusion protein is found in human myeloid leukemia and
      Ewing's sarcoma as a result of specific chromosomal translocation. To unveil the
      potential mechanism(s) underlying cellular transformation, we have investigated
      the effects of TLS-ERG on both gene transcription and RNA splicing. Here we show
      that the TLS protein forms complexes with RNA polymerase II (Pol II) and the
      serine-arginine family of splicing factors in vivo. Deletion analysis of TLS-ERG
      in both mouse L-G myeloid progenitor cells and NIH 3T3 fibroblasts revealed that
      the RNA Pol II-interacting domain of TLS-ERG resides within the first 173 amino
      acids. While TLS-ERG repressed expression of the luciferase reporter gene driven
      by glycoprotein IX promoter in L-G cells but not in NIH 3T3 cells, the fusion
      protein was able to affect splicing of the E1A reporter in NIH 3T3 cells but not
      in L-G cells. To identify potential target genes of TLS-ERG, the fusion protein
      and its mutants were stably expressed in both L-G and NIH 3T3 cells through
      retroviral transduction. Microarray analysis of RNA samples from these cells
      showed that TLS-ERG activates two different sets of genes sharing little
      similarity in the two cell lines. Taken together, these results suggest that the
      oncogenic TLS-ERG fusion protein transforms hematopoietic cells and fibroblasts
      via different pathways.

PMID- 15988033
TI  - Gamma interferon-inducible protein 10 induces HeLa cell apoptosis through a p53
      dependent pathway initiated by suppression of human papillomavirus type 18 E6 and
      E7 expression.
AB  - Gamma interferon-inducible protein 10 (IP10) is a member of the CXC family of
      chemokines. By differential mRNA display, we have demonstrated the upregulation
      of IP10 in coxsackievirus B3 (CVB3)-infected mouse hearts. Functional
      characterization of the IP10 gene in IP10-transfected Tet-On HeLa cells has found
      that IP10 induced cell apoptosis and inhibited viral replication. In the
      characterization of the IP10-induced apoptotic pathway, we found that
      overexpression of IP10 upregulated p53 and resulted in altered expression of p53
      responsive genes such as the p21Cip1, p27kip1, NF-kappaB, Bax, and PUMA genes and
      the mitochondrial translocation of Bax. However, transduction of the IP10 cells
      with adenovirus expressing dominant negative p53 not only ablated p53-triggered
      gene expression but also abolished IP10-induced apoptosis and restored CVB3
      replication to the control levels. These data suggest a novel mechanism by which
      IP10 inhibits viral replication through the induction of host cell death via a
      p53-mediated apoptotic pathway. We also found that constantly high-level
      expression of p53 in these tumor cells is attributed to the IP10-induced
      suppression of human papillomavirus E6 and E7 oncogene expression. Taken
      together, these data reveal not only a previously unrecognized link between
      chemokine IP10 and p53 in antiviral defense but also a mechanism by which IP10
      inhibits tumor cell growth.

PMID- 15988034
TI  - Inhibiting myosin light chain kinase induces apoptosis in vitro and in vivo.
AB  - Previous short-term studies have correlated an increase in the phosphorylation of
      the 20-kDa light chain of myosin II (MLC20) with blebbing in apoptotic cells. We
      have found that this increase in MLC20 phosphorylation is rapidly followed by
      MLC20 dephosphorylation when cells are stimulated with various apoptotic agents.
      MLC20 dephosphorylation is not a consequence of apoptosis because MLC20
      dephosphorylation precedes caspase activation when cells are stimulated with a
      proapoptotic agent or when myosin light chain kinase (MLCK) is inhibited
      pharmacologically or by microinjecting an inhibitory antibody to MLCK. Moreover,
      blocking caspase activation increased cell survival when MLCK is inhibited or
      when cells are treated with tumor necrosis factor alpha. Depolymerizing actin
      filaments or detaching cells, processes that destabilize the cytoskeleton, or
      inhibiting myosin ATPase activity also resulted in MLC20 dephosphorylation and
      cell death. In vivo experiments showed that inhibiting MLCK increased the number
      of apoptotic cells and retarded the growth of mammary cancer cells in mice. Thus,
      MLC20 dephosphorylation occurs during physiological cell death and prolonged
      MLC20 dephosphorylation can trigger apoptosis.

PMID- 15988035
TI  - Cardiac tissue-specific repression of CELF activity disrupts alternative splicing
      and causes cardiomyopathy.
AB  - Members of the CELF family of RNA binding proteins have been implicated in
      alternative splicing regulation in developing heart. Transgenic mice that express
      a nuclear dominant-negative CELF protein specifically in the heart (MHC
      CELFDelta) develop cardiac hypertrophy and dilated cardiomyopathy with defects in
      alternative splicing beginning as early as 3 weeks after birth. MHC-CELFDelta
      mice exhibit extensive cardiac fibrosis, severe cardiac dysfunction, and
      premature death. Interestingly, the penetrance of the phenotype is greater in
      females than in males despite similar levels of dominant-negative expression,
      suggesting that there is sex-specific modulation of splicing activity. The
      cardiac defects in MHC-CELFdelta mice are directly attributable to reduced levels
      of CELF activity, as crossing these mice with mice overexpressing CUG-BP1, a wild
      type CELF protein, rescues defects in alternative splicing, the severity and
      incidence of cardiac hypertrophy, and survival. We conclude that CELF protein
      activity is required for normal alternative splicing in the heart in vivo and
      that normal CELF-mediated alternative splicing regulation is in turn required for
      normal cardiac function.

PMID- 15988036
TI  - Platelet-derived growth factor D is activated by urokinase plasminogen activator
      in prostate carcinoma cells.
AB  - Platelet-derived growth factor (PDGF) protein family members are potent mitogens
      and chemoattractants for mesenchymal cells. The classic PDGF ligands A and B are
      single-domain protein chains which are secreted as active dimers capable of
      activating their cognate PDGF receptors (PDGFRs). In contrast to PDGFs A and B,
      PDGF D contains an N-terminal complement subcomponent C1r/C1s, Uegf, and Bmp1
      (CUB) domain and a C-terminal PDGF domain. PDGF D must undergo extracellular
      proteolytic processing, separating the CUB domain from the PDGF domain, before
      the PDGF domain can stimulate beta-PDGFR-mediated cell signal transduction. Here,
      we report that prostate carcinoma cells LNCaP and PC3 autoactivate latent full
      length PDGF D into its active form under serum-independent conditions and that
      this autoactivation is inhibited by PAI-1, a urokinase plasminogen activator
      (uPA)/tissue plasminogen activator (tPA) inhibitor. Interestingly, uPA, but not
      the closely related protease tPA, is capable of processing recombinant latent
      PDGF DD into the active form. We identify the uPA cleavage site between the CUB
      and PDGF domains of the full-length PDGF D by mutational analysis and show that
      PDGF D and uPA colocalize in human prostate carcinoma. This evidence provides a
      direct link between uPA- and PDGF D-mediated cell signaling, which may contribute
      to the progression of prostate cancer.

PMID- 15988037
TI  - Impaired mitotic progression and preimplantation lethality in mice lacking OMCG1,
      a new evolutionarily conserved nuclear protein.
AB  - While highly conserved through evolution, the cell cycle has been extensively
      modified to adapt to new developmental programs. Recently, analyses of mouse
      mutants revealed that several important cell cycle regulators are either
      dispensable for development or have a tissue- or cell-type-specific function,
      indicating that many aspects of cell cycle regulation during mammalian embryo
      development remain to be elucidated. Here, we report on the characterization of a
      new gene, Omcg1, which codes for a nuclear zinc finger protein. Embryos lacking
      Omcg1 die by the end of preimplantation development. In vitro cultured Omcg1-null
      blastocysts exhibit a dramatic reduction in the total cell number, a high mitotic
      index, and the presence of abnormal mitotic figures. Importantly, we found that
      Omcg1 disruption results in the lengthening of M phase rather than in a mitotic
      block. We show that the mitotic delay in Omcg1-/- embryos is associated with
      neither a dysfunction of the spindle checkpoint nor abnormal global histone
      modifications. Taken together, these results suggest that Omcg1 is an important
      regulator of the cell cycle in the preimplantation embryo.

PMID- 15988039
TI  - The impact of the NIH public access policy on literature informatics: What role
      can the neuroinformaticists play?

PMID- 15988041
TI  - Comparison of vector space model methodologies to reconcile cross-species
      neuroanatomical concepts.
AB  - Generating informational thesauri that classify, cross-reference, and retrieve
      diverse and highly detailed neuroscientific information requires identifying
      related neuroanatomical terms and acronyms within and between species (Gorin et
      al., 2001) Manual construction of such informational thesauri is laborious, and
      we describe implementing and evaluating a neuroanatomical term and acronym
      reconciliation (NTAR) system to assist domain experts with this task. NTAR is
      composed of two modules. The neuroanatomical term extraction (NTE) module employs
      a hidden Markov model (HMM) in conjunction with lexical rules to extract
      neuroanatomical terms (NT) and acronyms (NA) from textual material. The output of
      the NTE is formatted into collections of term- or acronym-indexed documents
      composed of sentences and word phrases extracted from textual material. The
      second information retrieval (IR) module utilizes a vector space model (VSM) and
      includes a novel, automated relevance feedback algorithm. The IR module retrieves
      statistically related neuroanatomical terms and acronyms in response to queried
      neuroanatomical terms and acronyms. Neuroanatomical terms and acronyms retrieval
      obtained from term-based inquiries were compared with (1) term retrieval obtained
      by including automated relevance feedback and with (2) term retrieval using
      "document-to-document" comparisons (context-based VSM). The retrieval of
      synonymous and similar primate and macaque thalamic terms and acronyms in
      response to a query list of human thalamic terminology by these three IR
      approaches was compared against a previously published, manually constructed
      concordance table of homologous cross-species terms and acronyms. Term-based VSM
      with automated relevance feedback retrieved 70% and 80% of these primate and
      macaque terms and acronyms, respectively, listed in the concordance table.
      Automated feedback algorithm correctly identified 87% of the macaque terms and
      acronyms that were independently selected by a domain expert as being appropriate
      for manual relevance feedback. Context-based VSM correctly retrieved 97% and 98%
      of the primate and macaque terms and acronyms listed in the term homology table.
      These results indicate that the NTAR system could assist neuroscientists with
      thesauri creation for closely related, highly detailed neuroanatomical domains.

PMID- 15988040
TI  - Statistical criteria in FMRI studies of multisensory integration.
AB  - Inferences drawn from functional magnetic resonance imaging (fMRI) studies are
      dependent on the statistical criteria used to define different brain regions as
      "active" or "inactive" under the experimental manipulation. In fMRI studies of
      multisensory integration, additional criteria are used to classify a subset of
      the active brain regions as "multisensory." Because there is no general agreement
      in the literature on the optimal criteria for performing this classification, we
      investigated the effects of seven different multisensory statistical criteria on
      a single test dataset collected as human subjects performed auditory, visual, and
      auditory- visual object recognition. Activation maps created using the different
      criteria differed dramatically. The classification of the superior temporal
      sulcus (STS) was used as a performance measure, because a large body of
      converging evidence demonstrates that the STS is important for auditory-visual
      integration. A commonly proposed criterion, "supra-additivity" or "super
      additivity", which requires the multisensory response to be larger than the
      summed unisensory responses, did not classify STS as multisensory. Alternative
      criteria, such as requiring the multisensory response to be larger than the
      maximum or the mean of the unisensory responses, successfully classified STS as
      multisensory. This practical demonstration strengthens theoretical arguments that
      the super-additivity is not an appropriate criterion for all studies of
      multisensory integration. Moreover, the importance of examining evoked fMRI
      responses, whole brain activation maps, maps from multiple individual subjects,
      and mixed-effect group maps are discussed in the context of selecting statistical
      criteria.

PMID- 15988043
TI  - A new era in computational neuroscience.

PMID- 15988044
TI  - Expression of foreign genes in Dunaliella by electroporation.
AB  - An electroporation procedure has been described for introducing plasmid DNA into
      Dunaliella salina cells. By this procedure, a bulk of plasmid DNA was delivered
      into the cells and retained for at least 3 d. Reverse transcriptase polymerase
      chain reaction (RT-PCR) and sequencing analyses indicated that the transcription
      and pre-mRNA splicing of ble gene (contributing the Zeocin resistance) were
      detected in the cells as early as 1 h after the electroporation. Individual
      colonies could retain the resistance to 10 mg/L Zeocin for at least 6 mo.
      Subsequent Southern blot analysis showed the existence of introduced plasmid DNA
      inside these colonies. However, most of the cells (approx 90%) lost the
      resistance in the presence of 5 mg/L Zeocin during subculturing, which was
      consistent with the observations of both rearranged and episomal plasmid DNA
      existed in the cells. Nevertheless, the electroporation procedure allows
      introducing a gene of interest and studying its expression and function in D.
      salina cells.

PMID- 15988042
TI  - Development of a model for microphysiological simulations: small nodes of ranvier
      from peripheral nerves of mice reconstructed by electron tomography.
AB  - The node of Ranvier is a complex structure found along myelinated nerves of
      vertebrate animals. Specific membrane, cytoskeletal, junctional, extracellular
      matrix proteins and organelles interact to maintain and regulate associated ion
      movements between spaces in the nodal complex, potentially influencing response
      variation during repetitive activations or metabolic stress. Understanding and
      building high resolution three dimensional (3D) structures of the node of
      Ranvier, including localization of specific macromolecules, is crucial to a
      better understanding of the relationship between its structure and function and
      the macromolecular basis for impaired conduction in disease. Using serial section
      electron tomographic methods, we have constructed accurate 3D models of the nodal
      complex from mouse spinal roots with resolution better than 7.5 nm. These
      reconstructed volumes contain 75-80% of the thickness of the nodal region. We
      also directly imaged the glial axonal junctions that serve to anchor the terminal
      loops of the myelin lamellae to the axolemma. We created a model of an intact
      node of Ranvier by truncating the volume at its midpoint in Z, duplicating the
      remaining volume and then merging the new half volume with mirror symmetry about
      the Z-axis. We added to this model the distribution and number of Na+ channels on
      this reconstruction using tools associated with the MCell simulation program
      environment. The model created provides accurate structural descriptions of the
      membrane compartments, external spaces, and formed structures enabling more
      realistic simulations of the role of the node in modulation of impulse
      propagation than have been conducted on myelinated nerve previously.

PMID- 15988045
TI  - Overexpression in Escherichia coli and functional reconstitution of anchovy
      trypsinogen from the bacterial inclusion body.
AB  - We have synthesized and optimized a high-yielding Escherichia coli expression
      system to produce trypsinogen from anchovy Engraulis japonicus and have developed
      conditions for its successful refolding. Recombinant anchovy trypsinogen
      precipitated in E. coli Rosetta (DE3) pLacI strain as inclusion bodies was
      denatured by 6 M guanidine-HCl followed by refolding with drop wise addition to a
      large excess of a folding buffer containing 0.5 M non-detergent sulfobetaine
      (NDSB-251) and a redox potential of oxidized and reduced glutathiones. The folded
      trypsinogen was autocatalytically activated to its mature form, trypsin, and
      purified with a MonoQ ion-exchange column. NH2-terminal amino acid sequencings
      revealed that E. coli efficiently processed NH2-terminal methionine residue from
      the expressed trypsinogen and that trypsinogen was activated at the correct site
      to generate active trypsin. The recombinant enzyme showed kinetic properties
      comparable to those of the native enzyme and demonstrated a typical cleavage
      preference for arginine over lysine residue against a protein substrate. The
      optimized expression and folding procedures yielded 12 mg of purified, active
      trypsin from 1 L of bacterial culture or 45 g wet weight cells, which is quite
      enough for various analytical and semipreparative purposes.

PMID- 15988046
TI  - Characterization of monoclonal antibodies against altered (T103I) amidase from
      Pseudomonas aeruginosa.
AB  - Monoclonal antibodies (MAbs) against mutant (T103I) amidase from Pseudomonas
      aeruginosa were raised by hybridoma technology. To select MAbs suitable for
      immunoaffinity chromatography, hybridoma clones secreting polyol-responsive MAbs
      (PR-MAbs) were screened that bind antigen tightly but release under mild and
      nondenaturing elution conditions. It was found that about 10% of enzyme-linked
      immunosorbent assay (ELISA)-positive hybridoma produce these MAbs as their ag-ab
      complex can be disrupted by propylene glycol in the presence of a suitable salt.
      Two of these hybridoma clones (F6G7 and E2A6) secreting PR-MAbs against mutant
      amidase were selected for optimization of experimental conditions for elution of
      amidase by using ELISA elution assay. These hybridoma cell lines secreted MAbs of
      IgM class that were purified in a single step by gel filtration chromatography,
      which revealed a single protein band on native polyacrylamide gel electrophoresis
      (PAGE). Specificity studies of this MAb revealed that it recognized specifically
      a common epitope on mutant and wild-type amidases as determined by direct ELISA.
      This MAb exhibited a higher affinity for denatured forms of wild-type and mutant
      amidases than for native forms as revealed by affinity constants (K), suggesting
      that it recognizes a cryptic epitope on an amidase molecule. Furthermore, MAb
      E2A6 inhibited about 60% of wild-type amidase activity, whereas it activated
      about 60% of mutant amidase (T103I) activity. The data presented in this work
      suggest that this MAb acts as a very useful probe to detect conformational
      changes in native and denatured amidases as well as to differentiate wild-type
      and mutant (T103I) amidases.

PMID- 15988047
TI  - An HIV-1 tat-autoantigen fusion protein suppresses insulitis in NOD mice.
AB  - To assess the immunomodulatory activity of the HIV Tat transduction peptide for
      enhancement of suppression of Type 1 autoimmune diabetes, the 11 amino acid HIV-1
      Tat transduction peptide was genetically linked to the major islet autoantigens
      proinsulin (INS) and glutamic acid decarboxylase (GAD). The Tat-autoantigen
      fusion proteins were synthesized in Escherichia coli and characterized by
      acrylamide gel separation and immunoblot analysis. Histological examination of
      pancreatic islets isolated from juvenile NOD mice inoculated orally with the Tat
      autoantigen conjugates revealed a significant reduction in islet inflammation
      (insulitis) in comparison with islets from unimmunized mice. Increased serum IgG1
      antibody isotype titers detected in Tat-autoantigen inoculated mice suggest that
      the transduction peptide-autoantigen fusion proteins stimulate Th2 lymphocyte
      mediated bystander suppression. The reduction of islet insulitis observed in Tat
      autoantigen inoculated mice suggests that the adjuvant effect of the Tat
      transduction peptide resides in Tat enhanced delivery of linked autoantigens
      through enterocytes to lymphocytes in the gut-associated lymphoid tissues.

PMID- 15988048
TI  - Differentiation response of acute promyelocytic leukemia cells and PML/RARa
      leukemogenic activity studies by real-time RT-PCR.
AB  - Acute promyelocytic leukemia (APL) is a human cancer generated by a chromosomal
      translocation t(15;17) involving the promyelocytic leukemia (PML) and retinoic
      acid receptor alpha (RARalpha) genes. The PML/RARalpha oncoprotein expressing
      blasts show two of the most important biological features of neoplastic
      progression: block of differentiation, at the promyelocytic state, and increased
      survival. Although PML/RARalpha interferes with the normal maturation of myeloid
      precursors to granulocytes, pharmacological doses of retinoic acid are sufficient
      to restore the differentiation processes. We designed an assay based on the Real
      Time reverse transcriptase polymerase chain reaction (RT-PCR) to experimentally
      follow the differentiation response of leukemic cells even after short-time
      differentiating treatments. Amplifying CD11b, CD11c, and CD14 mRNAs, as specific
      markers of differentiation, by the real-time RT-PCR assay we could detect both
      retinoic acid (RA) and vitamin D3 and human transforming growth factor beta1
      (VitD3/TGFbeta1) induced cellular maturation more precociously than the canonical
      flow-cytofluorimetric assay. Moreover, by amplifying CD14 mRNA it was possible to
      monitor the ability of PML/RARalpha oncoprotein to block VitD3/TGFbeta1 induced
      differentiation in U937-PR9 promonocytic inducible model systems.The proposed
      real-time quantitative RT-PCR approach is a reproducible and highly sensitive
      assay and can be considered a valid method to study both cellular maturation
      state and differentiation response.

PMID- 15988049
TI  - Storage and retrieval of microarray data and open source microarray database
      software.
AB  - Microarray technology has been widely adopted by researchers who use both home
      made microarrays and microarrays purchased from commercial vendors. Associated
      with the adoption of this technology has been a deluge of complex data, both from
      the microarrays themselves, and also in the form of associated meta data, such as
      gene annotation information, the properties and treatment of biological samples,
      and the data transformation and analysis steps taken downstream. In addition,
      standards for annotation and data exchange have been proposed, and are now being
      adopted by journals and funding agencies alike. The coupling of large quantities
      of complex data with extensive and complex standards require all but the most
      small-scale of microarray users to have access to a robust and scaleable database
      with various tools. In this review, we discuss some of the desirable properties
      of such a database, and look at the features of several freely available
      alternatives.

PMID- 15988050
TI  - Flavonoid compounds in maintenance of prostate health and prevention and
      treatment of cancer.
AB  - Compounds based on a flavonoid (di-phenolic) ring structure are emerging as a
      potentially important new class of pharmaceutical compounds with a broad range of
      biological activities, most prominent of which are their potential role as
      anticancer agents. These compounds exert a wide range of upregulating and
      downregulating effects on signal transduction processes within cells in both
      plants and animals. The observation that human communities, which consume large
      quantities of these compounds (legume-based vegetarian diets), have a lower
      incidence of many degenerative diseases and some cancers has led to the
      speculation that these compounds, or synthetic analogs, may be of therapeutic
      value. This article reviews the evidence supporting this hypothesis and provides
      some examples of attempts to develop new therapeutics based on dietary
      isoflavones or novel isoflavonoid structures in maintaining prostate health and
      in cancer treatment and management. One of these compounds, phenoxodiol, is now
      in human clinical trials and has shown promise in patients with recurrent ovarian
      cancer where the cancer is refractory or resistant to standard chemotherapy, and
      in patients with hormone-refractory prostate cancer.

PMID- 15988051
TI  - Study of cyclic adenosine monophosphate microdomains in cells.
AB  - Cyclic adenosine monophosphate (cAMP) controls the physiological response to many
      diverse extracellular stimuli. To maintain signal specificity, cAMP-mediated
      signaling is finely tuned by means of a complex array of proteins that control
      the spatial and temporal dynamics of the second messenger within the cell. To
      unravel the way a cell encodes cAMP signals, new biosensors have recently been
      introduced that allow imaging of the second messenger in living cells with high
      spatial resolution. The more recent generation of such biosensors exploits the
      phenomenon of fluorescence resonance energy transfer between the green
      fluorescent protein- tagged subunits of a chimeric protein kinase A, as the way
      to visualize and measure the dynamic fluctuations of cAMP. This chapter describes
      the molecular basis on which such a genetically encoded cAMP sensor relies and
      the tools and methods required to perform cAMP measurements in living samples.

PMID- 15988053
TI  - Cygnets: in vivo characterization of novel cGMP indicators and in vivo imaging of
      intracellular cGMP.
AB  - The second messenger cyclic guanosine 5'-monophosphate (cGMP) plays a key role in
      the control and regulation of a steadily increasing number of diverse
      physiological processes. As the appreciation of the importance of understanding
      the cGMP signaling pathway has grown, so has the awareness of the limited
      techniques with which to study the rapid intracellular cGMP kinetics. We have
      previously demonstrated the construction of cygnets, cGMP indicators using energy
      transfer comprised of cyan and yellow variants of green fluorescent protein
      flanked by conformationally sensitive cGMP receptor portion taken from the cGMP
      dependent protein kinase. Here, we report that cGMP binds to Cygnet-2.1,
      utilizing ECFP and Citrine, with an apparent equilibrium-binding constant of 600
      nM causing a total fluorescence intensity ratio change of 45%. In contrast, cAMP
      could elicit a maximal 10% change in fluorescence resonance energy transfer
      (FRET) ratio, demonstrating an approx 500-fold selectivity for cGMP. When
      expressed in vascular smooth muscle cells, cygnets demonstrated even cytosolic
      distribution and nuclear exclusion. Cultured rat aortic smooth muscle cells,
      which exhibit a noncontractile, synthetic phenotype typically seen in response to
      atherosclerosis or vascular injury, responded to natriuretic peptide (BNP)
      mediated activation of the particulate guanylyl cyclase. In conclusion, cygnets
      have facilitated the temporal resolution and evaluation of the contributions of
      cyclases and phosphodiesterases in determining overall cGMP accumulation, and the
      visualization of novel spatial dynamics that will contribute to more fully
      understanding the role of cGMP in the mediation of smooth muscle relaxation.

PMID- 15988052
TI  - High-resolution measurements of cyclic adenosine monophosphate signals in 3D
      microdomains.
AB  - A large number of hormones, neurotransmitters, and odorants exert their effects
      on cells by triggering changes in intracellular levels of cyclic adenosine
      monophosphate (cAMP). Although the effector proteins that bind cAMP have been
      identified, it is not known how this single messenger can differentially regulate
      the activities of hundreds of cellular proteins. It has been clear, for some
      time, that compartmentation of cAMP signals must be taking place, but the
      physical basis for compartmentation and the nature of local cAMP signals are
      mostly unknown. We present here a high-resolution method for measuring cAMP
      signals near the membrane in single cells. Cyclic nucleotide-gated (CNG) ion
      channels from olfactory receptor neurons have been genetically modified to
      improve their cAMP-sensing properties. We outline how these channels can be used
      in electrophysiological experiments to measure accurately changes in cAMP
      concentration near the membrane, where most adenylyl cyclases reside. We also
      describe how the method has been employed to dissect the roles of diffusion
      barriers and differential phosphodiesterase activity in creating distinct cAMP
      signals. This approach has much greater spatial and temporal resolution than
      other methods for measuring cAMP and should help to unravel the complexities of
      signaling by this ubiquitous messenger.

PMID- 15988054
TI  - High-throughput screening of phosphodiesterase activity in living cells.
AB  - Phosphodiesterases (PDEs) hydrolyze the second messengers cyclic adenosine
      monophosphate (cAMP) and cyclic guanosine 5'-monophosphate (cGMP) and play a
      crucial role in the termination and spatial segregation of cyclic nucleotide
      signals. Despite a wealth of molecular information, very little is known about
      how PDEs regulate cAMP and cGMP signals in living cells because conventional
      methods lack the necessary spatial and temporal resolution. We present here a
      sensitive optical method for monitoring cAMP levels and PDE activity near the
      membrane, using cyclic nucleotide-gated (CNG) ion channels as sensors. These
      channels are directly opened by the binding of cyclic nucleotides and allow
      cations to cross the membrane. The olfactory channel A subunit (CNGA2) has been
      genetically modified to improve its cAMP sensitivity and specificity. Channel
      activity is assessed by measuring Ca2+ influx using standard fluorometric
      techniques. In addition to studying PDEs in their native setting, the approach
      should be particularly useful in high-throughput screening assays to test for
      compounds that affect PDE activity, as well as the activities of the many G
      protein-coupled receptors that cause changes in intracellular cAMP.

PMID- 15988055
TI  - Assessment of phosphodiesterase isozyme contribution in cell and tissue extracts.
AB  - Cyclic nucleotide phosphodiesterases (PDEs), which are ubiquitously distributed
      in mammalian tissues, play a major role in cell signaling by hydrolyzing cyclic
      adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate. Owing to
      their diversity, which allows specific distribution at the cellular and
      subcellular level, PDEs can selectively regulate various cellular functions. We
      present here a convenient and sensitive radioenzymatic assay for characterizing
      and determining the contribution of the various PDE families in cell and tissue
      extracts. This assay is based on the knowledge and use of chosen PDE family
      specific inhibitors in order to determine the distinct PDE isozyme contribution
      in the overall cyclic nucleotide hydrolyzing activity. It can be used to
      characterize total, cytosolic, and membrane-associated PDE activities, as well as
      PDEs associated with purified subcellular structures. This approach is useful for
      comparing data of control and treated extracts and is therefore quite valuable
      for viewing the PDE status in different physiopathological conditions.

PMID- 15988056
TI  - Localization of cyclic guanosine 3',5'-monophosphate-hydrolyzing
      phosphodiesterase type 9 in rat brain by nonradioactive in situ hydridization.
AB  - In this chapter, we describe a protocol for the localization of the cyclic
      guanosine 3',5'-monophosphate-specific phosphodiesterase type 9 (PDE9) mRNA in
      the adult rat brain that uses digoxigenin-labeled riboprobes in a nonradioactive
      in situ hybridization (ISH). The three different riboprobes used all showed
      similar PDE9 mRNA expression patterns, detecting PDE9 in cell bodies throughout
      the whole brain. By using immunocytochemical double labeling of the ISH sections
      with the neuronal marker NeuN or the glial cell marker glial fibrillary acidic
      protein, the cells expressing PDE9 mRNA were further characterized. Double
      labeling experiments revealed that PDE9 was predominantly expressed in neurons.

PMID- 15988058
TI  - Adenovirus-mediated overexpression of murine cyclic nucleotide phosphodiesterase
      3B.
AB  - To construct the recombinant adenovirus vector containing the cDNA for
      recombinant mouse cyclic nucleotide phosphodiesterase 3B (mPDE3B), the cDNA for
      mPDE3B was subcloned into pACCMV.pLpA. Subsequently, this recombinant plasmid,
      pACCMV.mPDE3B, was cotransfected with pJM17 plasmid containing the adenoviral
      genome into 293 human embryonic kidney cells, and the replication-deficient
      adenovirus AdCMV.mPDE3B was generated via homologous recombination. Large-scale
      preparation of adenovirus yielded 10(11)-10(13) viral particles/mL and could be
      quantitated by real-time polymerase chain reaction using iCycler (Bio-Rad).
      Efficiency of gene transfer was assessed by infecting FDCP2 or H4IIE cells with a
      recombinant adenovirus expressing beta-galactosidase (beta-gal); greater than 75%
      of cells were infected. Expression of mPDE3B in H4IIE hepatoma cells, FDCP2
      hematopoietic cells, and beta-cells from isolated pancreatic islets was detected
      by Western blot analysis. In lysates from FDCP2 cells and H4IIE hepatoma cells
      infected with recombinant adenoviral mPDE3B constructs, mPDE3B activity was
      increased 10- to 30-fold compared with the activity in lysates from cells
      infected with beta-gal adenovirus. Stimulation of FDCP2 cells infected with
      mPDE3B adenovirus with insulin (100 nM, 10 min) resulted in an approx 1.7-fold
      increase in endogenous PDE3B and recombinant wild-type PDE3B activities.
      Infection of rat pancreatic islets resulted in a 5- to 10-fold increase in PDE3B
      expression and activity and subsequent blunting of insulin secretion. Thus,
      adenovirus-mediated gene transfer is effective for studying expression and
      regulation of recombinant PDE3 in insulin-responsive cells as well as insulin
      secreting cells.

PMID- 15988057
TI  - Determination of Ca2+/calmodulin-stimulated phosphodiesterase activity in intact
      cells.
AB  - Ca(2+)/calmodulin (CaM)-stimulated phosphodiesterases (PDEs) constitute a large
      family (PDE1 family) of enzymes. All members of the PDE1 family can be stimulated
      by Ca(2+) in the presence of CaM in vitro. It has been shown that the Ca(2+)/CaM
      stimulated PDE activity present in the vessel wall or vascular smooth muscle
      cells can be stimulated in vivo by contracting reagents that increase
      intracellular Ca(2+) concentrations. We describe in detail a technique used to
      estimate the extent of PDE1 activation in vivo by measuring in vitro the PDE
      activity that represents the extent of association between Ca(2+)-CaM and PDE1 in
      vivo. The technique involves the extraction and rapid assay of enzyme activity at
      a low temperature and in the presence of trifluoperazine to minimize the changes
      in association between Ca(2+)-CaM and the PDE1 family member during cell lysis
      and assaying activity. This technique can be used to measure Ca(2+)/CaM
      stimulated PDE activity in cultured cells or tissues.

PMID- 15988059
TI  - Identification of promoter elements in 5'-flanking region of murine cyclic
      nucleotide phosphodiesterase 3B gene.
AB  - We describe techniques for identifying functional promoter elements in the 5'
      flanking region of the murine cyclic nucleotide phosphodiesterase 3B (mPDE3B)
      gene. The 5'-flanking region of the mPDE3B gene was cloned and sequenced, and
      putative transcription factor binding sites were identified with computational
      tools. A series of reporter plasmids containing the luciferase gene fused to
      different fragments of the 5'-flanking region of the mPDE3B gene was constructed
      and used to transfect 3T3-L1 fibroblasts or differentiating adipocytes. Reporter
      gene assays showed that there are two promoter regions in the 5'-flanking region
      in the mPDE3B gene: a distal region located approx 4 kb upstream of the
      translation initiation site that contains cAMP-response element (CRE) cis-acting
      elements, and a proximal region that is GC rich and lacks TATA sequences. The
      distal promoter region induced much higher luciferase activity than did the
      proximal one. Mutation of the CRE sequences or reversal of the orientation of the
      CRE-containing region abolished promoter activity of the distal region.
      Electrophoretic mobility shift assay analysis indicated that binding to CRE
      elements was greater in nuclear extracts from differentiating adipocytes than
      from fibroblasts. Mapping of transcription initiation sites suggested that the
      distal promoter region might function as an enhancer, whereas the proximal
      promoter drives transcription of the mPDE3B gene.

PMID- 15988061
TI  - Cyclic guanosine 5'-monophosphate binding to regulatory GAF domains of
      photoreceptor phosphodiesterase.
AB  - Of the 11 families of mammalian cyclic nucleotide phosphodiesterases (PDEs), 5
      contain regulatory domains capable of binding cyclic guanosine 5'-monophosphate
      (cGMP). The best understood of the GAF-containing PDEs is the family of rod
      (PDE6R) and cone (PDE6C) photo receptor PDEs. Binding of cGMP to the rod PDE6
      catalytic dimer (alphabeta) allosterically regulates the affinity of the
      inhibitory subunits of PDE6 (gamma) for the enzyme. Two nonidentical, high-
      affinity cGMP-binding sites exist on the nonactivated mammalian PDE6R holoenzyme
      (alphabetagammagamma). One of the sites does not readily exchange with free cGMP
      when the catalytic dimer is complexed with Pgamma. On dissociation of gamma from
      the catalytic dimer, one of the two cGMP-binding sites undergoes a transition
      from high to low affinity. This chapter describes techniques to quantify cGMP
      binding to PDE6 in order to study the regulatory significance of the GAF domains.
      For high-affinity cGMP binding sites on PDE6, membrane filtration is the method
      of choice because of its speed, simplicity, and sensitivity. However, lower
      affinity cGMP-binding sites require a method that does not perturb the
      equilibrium between bound and free ligand. The use of ammonium sulfate solutions
      during filtration extends to lower-binding affinities the useful range of
      membrane filtration. However, a centrifugal separation technique that minimizes
      perturbation of the cGMP-binding equilibrium is also presented for measuring
      lower-affinity cGMP-binding sites. These methods are applicable to understanding
      the regulatory mechanisms regulating other GAF-containing PDEs as well.

PMID- 15988062
TI  - Renaturation of the catalytic domain of PDE4A expressed in Escherichia coli as
      inclusion bodies.
AB  - Owing to simplicity, speed, cost advantage, and a generally high product yield,
      expression in Escherichia coli is the method of choice for the production of
      large amounts of protein. However, because of the high expression level, proteins
      often accumulate within the cells as insoluble aggregates called inclusion
      bodies. The inclusion body protein is misfolded and biologically inactive and,
      thus, needs to be refolded into its native conformation. There is no universal
      method for refolding inclusion bodies and optimal conditions have to be
      determined empirically for any given protein. Here, we describe a simple and
      efficient refolding protocol for the catalytic domain of type 4 cyclic nucleotide
      phosphodiesterases (PDE4s). This method has the potential for adaptation to other
      PDE subtypes.

PMID- 15988060
TI  - Purification of PDE6 isozymes from mammalian retina.
AB  - The photoreceptor phosphodiesterase (PDE6) is the central effector of visual
      transduction in vertebrate retinal photoreceptors. Distinct isozymes of PDE6
      exist in rods and cones. Mammalian retina serves as an abundant source of tissue
      for PDE6 purification. Methods are described for the isolation and purification
      of membrane-associated PDE6 from rod outer segment membranes. Purification of
      cone PDE6 from the soluble fraction of retinal extracts is also described.
      Several procedures that can purify the rod and cone isozymes to homogeneity,
      including anion exchange, hydrophobic interaction, gel filtration,
      hydroxyapatite, and immunoaffinity chromatography, are presented. A method to
      activate PDE6 by limited proteolysis of its inhibitory gamma-subunit is also
      provided.

PMID- 15988063
TI  - Determining the subunit structure of phosphodiesterases using gel filtration and
      sucrose density gradient centrifugation.
AB  - Size-exclusion chromatography (gel filtration) is a widely used method to
      determine the molecular weight of a protein. Often, the elution volume of several
      standard proteins is plotted against their known molecular weight to generate a
      standard curve, which is then used to determine the molecular weight of the
      protein of interest by its elution volume. However, gel filtration does not
      measure the mass of a particle as such, but the Stokes radius (Rs), a property
      dependent on mass, shape, and hydration of a protein. Thus, this method works
      well only if the protein of interest has a spherical symmetrical shape and an
      average hydration level. For all other proteins, the use of gel filtration as the
      sole means to determine the molecular weight will be misleading. The molecular
      weight of any given protein can be calculated, however, using the method of
      Siegel and Monty. This method combines Stokes radii obtained from gel filtrations
      and sedimentation coefficients derived from density gradient centrifugations to
      calculate the mass of a protein independently of its shape or hydration. It has
      been shown previously that PDE4D3, a representative of the long PDE4 splice
      forms, behaves as a dimer, whereas PDE4D2, a prototype of the short PDE4 splice
      forms, is a monomer. Both proteins exhibit an anomalous behavior on gel
      filtration columns. For this reason, they are used in this study to demonstrate
      the necessity of performing both gel filtration and density gradient
      centrifugation to determine the molecular weight of a protein.

PMID- 15988064
TI  - Crystallization of cyclic nucleotide phosphodiesterases.
AB  - Selective inhibitors of cyclic nucleotide phosphodiesterases (PDEs) have been
      widely studied as therapeutic agents for the treatment of various human diseases.
      Three-dimensional structures are essential for the design of highly selective
      inhibitors, but their availability is limited by the speed of crystallization. We
      describe crystallization of the catalytic domains of the unligated PDE4B2B,
      rolipram-bound PDE4D2, and 3-isobutyl-1-methylxanthine-bound PDE5A1 using the
      methods of vapor diffusion and microdialysis. We also briefly describe general
      methods of protein crystallization to provide a background to readers outside of
      the crystallographic field. Finally, we discuss detailed procedures for and
      pitfalls of the crystallization of PDEs, which may be valuable for
      crystallization of other PDE members.

PMID- 15988065
TI  - Generation of PDE4 knockout mice by gene targeting.
AB  - The development of gene-targeting techniques has ushered in a new era in mouse
      genetics. Two discoveries have been instrumental: the finding that an exogenous
      DNA introduced in mammalian cells can recombine with homologous chromosomal
      sequences, a process known as gene targeting, and the revelation that cultured
      embryonic stem (ES) cells when injected into early stage mouse embryos can
      contribute to produce germ-line chimeras. On the basis of these seminal findings,
      gene targeting by homologous recombination in mouse ES cells in vitro has been
      established as a powerful means of altering specific loci in the mouse genome. As
      a result, gene function can be studied in vivo. By applying this technology,
      targeted disruption of PDE4 alleles is created in cultured ES cells and,
      subsequently, the mutant ES cells are injected into blastocysts and returned to
      pseudopregnant foster mothers to produce germ-line chimeric pups. In this
      chapter, we describe the basic protocols used to generate the PDE4 knockout mice.

PMID- 15988066
TI  - Immunoprecipitation of PDE2 phosphorylated and inactivated by an associated
      protein kinase.
AB  - A PDE2A2-associated protein kinase phosphorylates PDE2A2 in vivo and in vitro to
      inhibit its catalytic activity. Rat brain PDE2A2 may be solubilized using nona
      (ethylene glycol) mono dodecyl ether (Lubrol 12A9). PDE2A2 exists in a complex
      with a protein kinase regulating its activity in an adenosine triphosphate
      dependent manner. When native or recombinant PDE2 is immunoprecipitated from PC12
      cells using an antibody to the amino terminus in a buffer containing Lubrol 12A9,
      protease inhibitors, and phosphatase inhibitors, a coimmunoprecipitating nerve
      growth factor-stimulated protein kinase acts to phosphorylate it. PDE2A2
      phosphoryla-tion occurs optimally at pH 6.5 in a sodium 2-(4-morpholino)-ethane
      sulfonate buffer with 5 mM MgCl2 and 1 mM Na3VO4. I describe protocols for
      producing an antibody to an amino-terminal bacterial fusion protein encoding
      amino acids 1-251 of PDE2A2 as well as the use of this antibody in
      immunoprecipitating a PDE2: tyrosine protein-kinase complex from rat brain or
      PC12 cells.

PMID- 15988067
TI  - Investigation of extracellular signal-regulated kinase 2 mitogen-activated
      protein kinase phosphorylation and regulation of activity of PDE4 cyclic
      adenosine monophosphate-specific phosphodiesterases.
AB  - Recently, it has been shown that enzymes of the cyclic adenosine monophosphate
      (cAMP)-specific phosphodiesterase (PDE) family 4 can be directly phosphorylated
      by extracellular signal-regulated kinase 2 (ERK2). Phosphorylation of PDE4s by
      ERK2 is dependent on two docking domains on either side of the target serine that
      allow specificity and high-fidelity binding of the kinase. The functional
      consequence of PDE4 phosphorylation by ERK is either an increase or a decrease in
      PDE activity, depending on whether the PDE4 contains only one of the upstream
      conserved regions (UCR1) that are typical of PDE4s or both (UCR1 and UCR2). We
      detail some of the methods that have been crucial in elucidating these important
      discoveries that represent a novel point of cross talk between the cAMP signaling
      system and the ERK mitogen-activated protein kinase cascade.

PMID- 15988068
TI  - Radiolabeled ligand binding to the catalytic or allosteric sites of PDE5 and
      PDE11.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) have been investigated for years as
      targets for therapeutic intervention in a number of pathophysiological processes.
      Phosphodiesterase-5 (PDE5), which is highly specific for guanosine 3'-5'-cyclic
      monophosphate (cGMP) at both its catalytic site and its allosteric sites, has
      generated particular interest because it is potently and specifically inhibited
      by three drugs: sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly-ICOS), and
      vardenafil (Levitra, Bayer GSK). Previously, we have used [(3)H]cGMP to directly
      study the interaction of cGMP with the allosteric sites of PDE5, but because cGMP
      binds with relatively low affinity to the catalytic site, it has been difficult
      to devise a binding assay for this particular binding reaction. This approach
      using measurement of radiolabeled ligand binding continues to allow us to more
      precisely define functional features of the enzyme. We now use a similar approach
      to study the characteristics of high-affinity [(3)H]inhibitor binding to the PDE5
      catalytic domain. For these studies, we have prepared [(3)H]sildenafil and
      [(3)H]tadalafil, two structurally different competitive inhibitors of PDE5. The
      results demonstrate that radiolabeled ligands can be used as probes for both
      catalytic site and allosteric site functions of PDE5. We describe herein the
      methods that we have established for studying the binding of radiolabeled ligands
      to both types of sites on PDE5. These techniques have also been successfully
      applied to the study of binding of radiolabeled PDE5 inhibitors to PDE11,
      suggesting that these methods are applicable to the study of other PDEs, and
      perhaps other enzyme families.

PMID- 15988069
TI  - Analysis of dimerization determinants of PDE6 catalytic subunits.
AB  - An absolute majority of cyclic nucleotide phosphodiesterases (PDEs) form
      catalytic dimers. The structural determinants and functional significance of PDE
      dimerization are poorly understood. Furthermore, all known dimeric PDEs with the
      exception of retinal rod guanosine 3',5'-cyclic-monophosphate PDE (PDE6) are
      homodimeric enzymes. Rod PDE6 is a catalytic heterodimer composed of alpha- and
      beta-subunits. Gel filtration, sucrose gradient centrifugation, and
      immunoprecipitation are standard techniques used to study dimerization of
      proteins. We successfully applied these methods to investigate dimerization of
      chimeric proteins between PDE6alphabeta and PDE5, which allowed us to elucidate
      the structural basis for heterodimerization of rod PDE6. This chapter outlines
      approaches to the investigation of PDE6 dimerization that can be utilized in a
      broader analysis of PDE dimerization.

PMID- 15988070
TI  - Interactions between catalytic and inhibitory subunits of PDE6.
AB  - Rod and cone photoreceptor guanosine 3'5'-cyclic-monophosphate phosphodiesterases
      (PDEs) are classified into the PDE6 family of cyclic nucleotide PDEs. A unique
      feature of the PDE6 enzymes is the presence of inhibitory gamma-subunits
      (Pgamma). The inhibitory interaction between Pgamma and the rod PDE6alphabeta
      catalytic subunits is critically important for understanding the mechanism of
      phototransduction. Recent insights into the molecular interface between Pgamma
      and PDE6alphabeta have been achieved using mutagenesis of Pgamma, fluorescence
      labeling, and crosslinking approaches.

PMID- 15988071
TI  - Purification, reconstitution on lipid vesicles, and assays of PDE6 and its
      activator G protein, transducin.
AB  - PDE6 in rod and cone photoreceptors is the principal effector of
      phototransduction. It is kept at a very low activity level in the dark, and in
      the light it is strongly activated by the guanosine 5'-triphosphate-bound form of
      the alpha-subunit of the G protein, transducin. Both transducin and PDE6 are
      peripheral proteins, and understanding both their interactions with one another
      and the roles of lipids in their function requires reconstituting purified
      proteins on the surfaces of defined lipid bilayers. We describe here methods for
      purifying the proteins, reconstituting them with vesicles, and assaying catalytic
      activity and binding.

PMID- 15988072
TI  - [Is there a rationale for use of antibiotics in hair transplantation surgery?].
AB  - Currently hair transplantation is the number one cosmetic surgical procedure in
      men. American Academy of Cosmetic Surgery (AACS) estimated that there were
      177,000 hair transplantation sessions done in the year 2000. As for other
      cutaneous surgery, various antibiotics are administered during hair
      transplantation to minimize complications. But the use of prophylactic
      antibiotics to avoid surgical side infection for clean surgical wounds remains
      controversial. Although antibiotic prophylaxis can decrease the incidence of
      surgical side infection, the benefits should be weighed against the risks of
      toxic and allergic reactions, dysbacteriosis, and the emergence of bacterial
      resistance. In any case most of surgeons routinely prescribe the use of
      antibiotics preoperatively (from 1 hour to 2 days before the procedure) and
      postoperatively (range 5-7 days) for all patients. The objective of this work was
      the complete clinical observation for surgical side infection risk assessment
      during large hair transplant sessions which would help us to answer the question:
      should the antibiotic prophylaxis be used routinely in hair transplant
      procedures? Three groups of study subjects were defined: first group--100
      patients who were operated in our clinic in 2002-2004 years. Number of
      transplanted FU per session varied between 350-4516 (average 1983+/-4,8). In this
      group antibiotics were not be administrated. Second group--100 patients who were
      operated in the same period with 2016+/-47 FU transplantation. In this group all
      patients received 1,0 gr. ceftriaxone (rocephin, Roche) before surgery and 1,0
      gr. ceftriaxone every day after surgery during 5 days. Third group--342 patients
      who were operated during 1999-2002 years with transplantation of 420-3000 FU
      (average 1411+/-3,9) per session. In this group all patients received Duracef 500
      mg (Bristol Mayers) twice per day after surgery during 1 week. Our observations
      demonstrated no accidents of surgical side infection or irritation of recipient
      side or central necrosis in first two groups. 7 cases of SSI and central necrosis
      were occurred in the third group, but the primary cause of these complications
      was due to the rough technique in creation of recipient sites (using N16 Nokor
      needle) or donor closure. Analysis of our clinical observations which has been
      continued for 6 years and included 542 cases, assures us that prophylactic
      prescription of antibiotics after hair transplantation is unnecessary especially
      during strict adherence to the aseptic rules.

PMID- 15988074
TI  - [Histological and morphological characteristics of the different stages of
      cervical glandular intraepithelial neoplasia].
AB  - Currently there is no world system classification of glandular hyperplasia of
      uterine cervix (endocervix). Different authors give nonmonosemantic estimations
      to each type of cervical hyperplasia. Cervical Glandular Intraepithelial
      Neoplasia (CGIN) or Glandular Dysplasia is considered as a precancerous lesion of
      endocervix. Morphometric investigations have shown that for estimation of the
      degree of the endocervical glandular and intraepithelial neoplasia it is
      necessary the quantitative evaluation of the following criteria: type of
      epithelium--prismal, columnar, estimation of nucl/cytopl index >1, <1, =1,
      stratification, hyperchromatosis, hypochromatosis, big nucleoli, small nucleoli,
      stromal/parenchimal index >1, <1, =1. Based on our observations we suppose that
      glandular neoplasia must be divided into low grade intraepithelial neoplasia 
      CGIN 1, and high grade intraepithelial neoplasia -CGIN 2, and CGIN 3.

PMID- 15988073
TI  - [Hemodynamics during arterial hypertension in pregnant women].
AB  - The aim of the study was to evaluate hemodynamic profile of arterial hypertension
      during pregnancy. The study group consisted of 84 pregnant women with arterial
      hypertension (age 29+/-3,6 years), control group included 21 healthy women (age
      20+/-1,3 years). In the study group the following subgroups were identified:
      chronic arterial hypertension (24 cases), preeclampsia (22 cases), combination of
      preeclampsia with chronic arterial hypertension (18 cases), gestational
      hypertension (20 cases). The status of hemodynamics was evaluated by Doppler
      echocardiography (Sonoline-elegra-Siemens, Germany). It was proved, that in the
      pregnant women with chronic hypertension, preeclampsia, combination of
      preeclampsia with chronic hypertension and gestational hypertension, high-output
      hemodynamic syndrome has been developed. Significant differences in diameter of
      the root of aorta, thickness of the posterior wall of the left ventricle and end
      diastolic volume of the left ventricle was revealed, those correlated with age of
      the arterial hypertension.

PMID- 15988076
TI  - [Usage of medicines inducing secretolisys in treatment of acute otitis media in
      children].
AB  - Acute otitis media is one of the most common diseases in childhood and
      adolescence. Its incorrect and non-rational treatment increases the frequency of
      complicated acute forms of the disease. Objective of the study was to define
      effectiveness of mucoregulatory medication (namely Sinupret produced by Bionorica
      A.G. Germany) for treatment of complicated forms of AOM along with antibiotics in
      children. The trial has been conducted at Tbilisi M. Guramishvili Pediatric
      Clinic. It represented a randomized controlled trial of two prescribing
      strategies for acute otitis media. The participants have been 64 children with
      AOM-preperforation stage. Among them 32 patients (study group) got oral
      antibiotics--Amoxicillin along with the mucoregulatory remedy (Sinupret) and the
      rest 32 patients (control group) received Amoxicillin orally (Amoxicillin was
      used 40-45 mg/kg/24 h in children and 1,5-3 g/24 h in adults) divided in three
      administrations. The clinical effect of treatment was assessed according to the
      following data: subjectively-complaints of patients; objectively-clinical
      examination data (otoscopy), blood test data; tympanometric data. Measurements
      have been conducted at the beginning of treatment, on the third, seventh days, at
      the end of the course of treatment and two weeks later. Subjectively patients
      complained about unbearable pains in the ear, anxiety, abrupt reduction of
      hearing, murmurs in the ears acquiring pulsative nature, high temperature. For
      the treatment of complicated forms of acute otitis media (III stage)
      mucoregulatory remedies in combination with antibiotics were quite effective. It
      reduces necessity of paracentesys; increases the efficiency of accompanying
      antibiotic therapy and reduces frequency of complications.

PMID- 15988075
TI  - [Principles of preoperative and postoperative management of patients with
      hypospadias].
AB  - Retrospective analysis of the operated patients (during 1995-2000) with different
      forms of the hypospadias have been performed. It was shown that early onset
      postoperative complications as well as remote complications (relapse of a
      meatostenosis, uric fistulas, a divergence of the lips of the wounds, urethral
      diverticulum, concrement formation and urethral pilosis) are associated with
      cutaneal insufficiency of the penis, low-quality suture material, and the age of
      patients (older than 4-6 years). On the basis of the analysis of unsuccessful
      surgical interventions authors have developed a complex of activities on
      prevention of complications at different stages of correction of the defect. At
      the same time new methods of one-stage surgery using new types of suture material
      and carrying out of operations in the age under 3-4 years have been introduced.
      In 309 patients operated during 2001-2004 significant decrease in the frequency
      of postoperative complications has been noted.

PMID- 15988077
TI  - [Definition of therapeutic effect of mildronate in patients with chronic heart
      failure].
AB  - In developed countries chronic heart failure (CHF) is one of the main reasons of
      death and physical disability. CHF affects approximately 1-2% of the population
      and its prevalence is still increasing. Today ACE inhibitors, beta-blockers,
      diuretics are the first line drugs in treatment of CHF. Mildronate is a new drug
      optimizing cardiac energy metabolism and could be an effective approach in CHF
      patients' management. The aim of the study was to investigate the efficacy and
      safety of mildronate in treatment of CHF (NYHA III-IV funct. class) patients. 110
      patients with CHF, stable on conventional treatment (diuretics, ACE inhibitors,
      beta-blokers, digoxin), were treated additionally with mildronate. Assessment was
      performed with clinical data, FC change, ECO-cardiography, 6-minute walk test.
      Mildronate showed to be an effective drug in complex treatment of chronic heart
      failure.

PMID- 15988078
TI  - Factors related to the process of seeking and completing treatment for drug abuse
      (qualitative methods in drug abuse research).
AB  - Numerous studies have demonstrated the effectiveness of drug abuse treatment. Yet
      many drug abusers do not enter treatment, many who do enter leave prematurely,
      and relapse following treatment is common. Understanding motivation for change
      and treatment readiness is key to understanding how to induct and engage drug
      users in treatment. To the extent that treatment programs focus initially on
      reducing drug use, rather than psychosocial problems that motivate individuals to
      seek treatment, treatment programs may fail to meet the primary needs of users
      and thus fail to attract or engage them. Outcomes of substance abuse treatment
      programs historically have been measured by successful program completion,
      reduced drug use and illegal activity, and improved social functioning
      (employment, education etc). There is minimal reference to client expectations of
      treatment and factors that influenced treatment-seeking behavior. Studies that
      have assessed client dropout from substance abuse treatment have generally
      focused upon quantitative measures that attempt to determine what types of
      clients drop out or stay, or what types of characteristics best predict client
      dropout. Qualitative methods are the most appropriate to fill these gaps in
      substance abuse treatment research.

PMID- 15988079
TI  - [Assessment of cortical bone mineral density and biochemical markers of bone
      metabolism in postmenopausal osteoporosis].
AB  - The aim of this study was to assess cortical bone mineral density and biochemical
      markers of bone metabolism according to age of patients and menopause in
      postmenopausal osteoporosis. 87 women aged 40-70 years with radiologically
      documented postmenopausal osteoporosis were studied. Standard radiological
      investigation of spine and ultrasound densitometry was performed. Magnetic
      resonance imaging computed tomography was provided in some cases for establishing
      the diagnosis of osteoporosis. SOS (speed of sound) of cortical bone was measured
      in the middle of the tibia by ultrasound densitometer-Sound Scan Compact (Myriad
      Israel). Significant correlations were not found between the radiological changes
      of the axial skeleton and peripheral cortical BMD. Our results showed that
      cortical BMD correlates with the age of menopause (p<0,001) and decreases as
      patients aged. The method of peripheral ultrasound cortical bone densitometry
      frequently leads to hypodiagnosis in postmenopausal osteoporosis (23%). Therefore
      this method could not be used as an independent diagnostic tool and can be used
      for screening the elderly patients. The investigation of biochemical markers of
      bone turnover showed significant decreases of osteocalcin in the group with the
      age of menopause more then 10 years (p<0,001) while significant changes in
      calcium urinary excretion were not identified. That enables us to assume that
      misbalance between bone resorbtion and formation increases according to the age
      of menopause, towards the bone resorbtion.

PMID- 15988081
TI  - [Mexidol in treatment of children with generalized epilepsy and febrile
      seizures].
AB  - The aim of our study was to estimate the role of Mexidol in ceasing of epileptic
      fits and improving electroencephalographic (EEG) pathological patterns in
      children. 120 patients with generalized epilepsy (from 4 to 16 years old) were
      investigated. All patients were treated by Depakin chrono 30 mg/kg. Children were
      divided into 2 groups: 1st--study group consisted of 60 children with combined
      treatment with Depakin and Mexidol (5 mg/kg). In the control group (60 children)
      treatment was performed only by Depakin. 100 children with the first episode of
      febrile seizures (from 6 months to 4 years old) were investigated. 50 children
      composed the study group with monotheraphy by Mexidol and 50 patients--the
      control group, without any treatment. The EEG examination was done by computer
      EEG Topography "Brain Surveyor Saico". Using Depakin in combination with Mexidol
      in the study group of patients with generalized epilepsy, improvement of clinical
      picture of disease and normalization of EEG patterns in 93% of cases has been
      observed. In the study group of patients with febrile seizures, normalization of
      EEG pathological patterns was observed in 82% cases and in 18% its improvement
      was seen. The relapse of seizures at high temperature was observed in 3 patients.
      In control group EEG patterns were improved only in 20%, in 48% no positive
      effect was observed and in 41% the worsening of EEG findings was seen. The
      relapse of febrile seizures was observed in 26 cases. Mexidol titrated to the
      target doze of 5mg/kg may be effective in combination with Depakin for treatment
      of patients with generalized epilepsy and as monotherapy in patients with first
      episode of febrile seizures.

PMID- 15988080
TI  - [MRI findings in patients with epilepsy debuting with febrile seizures].
AB  - One of the most controversial issues in epilepsy research is whether prolonged
      febrile seizures (FS) cause mesial temporal sclerosis (MTS) and temporal lobe
      epilepsy (TLE). Mesial temporal sclerosis is the pathological substrate found in
      patients with TLE and history of FS. The reasons that determine development of
      TLE and FC are presented by two main groups: perinatal and postnatal. 16 patients
      with TLE were examined to study the relation between FC and MTS. 10 patients
      (62,5%) had a history of complex febrile convulsions (with prolonged duration,
      focal features, posttical periods). We present specific magnetic resonance
      characteristics of mesial temporal sclerosis. Temporal size decrease and
      ipsilateral dilatation of the inferior horn of lateral ventricle were identified
      as specific MTS markers. One of the most characteristic magnetic resonance (MR)
      findings in temporal lobe epilepsy patients with FC is a high-signal area
      observable on T2-weighted images, mainly in the mesial temporal region.

PMID- 15988082
TI  - [Neurological symptoms of cytomegalovirus infection in children].
AB  - Cytomegalovirus is considered as one of the most common causes of congenital
      infections. Clinical signs of infection are present in newborns whose mothers
      were infected during pregnancy. Disease is most severe if mother were infected
      during the first trimester. Congenital cytomegalovirus infection causes damage of
      CNS (central nervous system) and the liver, atrophy of optical nerve and hearing
      retardation up to complete loss. The most severe and frequent damage is of CNS.
      Under our observation were 20 children of different ages, among them 8 newborns.
      Verification of cytomegalovirus infection was done by ELISA. Polymerase Chain
      Reaction (PCR) was also used for diagnostic reasons. Examination of CNS was
      performed by neurosonography, electroencephalography and computed tomography.
      Four from eight newborns died at the age of 6-8 weeks (in these cases the
      generalized form of infection with severe damage of CNS was present). In the rest
      patients treatment with specific anticytomegalovirus immunoglobulin together with
      syndrome therapy yielded positive effect. Lately moderate retardation of
      phychomotor development became apparent in all cases. 12 patients, who come to
      our clinic in the period from 2 months to 1.5 years of age, psychomotor
      retardation, micro or hydrocephaly, hyperkinesias, absentia (epileptica),
      convulsive syndrome and malignant hypertension were present. On tomograms
      intracranial calcificats and cysts, also atrophy of cerebrum and encephalomalacia
      was visible. Sensory hearing loss was apparent in two patients. The study showed
      the presence of severe and in most cases irreversible CNS damages in the cases of
      congenital cytomegalovirus infection.

PMID- 15988083
TI  - [Functional morphology of adrenal cortex in aging rat under the influence of
      barocameral hypoxia].
AB  - The aim of the study was the assessment of adrenocorticocytes morphology in aging
      rat under the influence of hypobaric hypoxia. Adrenocorticocytes samples were
      collected from 11-18 months age 15 albino males under chronic hypobaric hypoxia
      of 60 days duration. The exposure time was 2 hours, pO2 was decreasing till 364
      372 mm Hg. Histology, histochemistry and electronmicroscopic techniques were used
      to assess the weight and thickness of adrenal cortex. Remarkable fibrosis,
      decreasing of weight (14%) and thickness of zone glomerulosa (37%) and z.
      fasciculata (24%) were detected. Involution of cells and cellular organelles
      (lipid droplets), activation of scavenger cells and secondary lysosomes play a
      crucial role in secretory function depletion of glandular cells. There were
      revealed the giant mitochondria in Z. glomerulosa glandular cells. Morphological
      analysis have shown the involutive influence of hypoxia on the adrenal cortex
      conditioned by age.

PMID- 15988084
TI  - [Adaptation of standard method of experimental burn injury for phagobioderm
      investigation].
AB  - The experimental study of thermal injury requires the use of different animal
      models in order to reproduce physiopathological conditions. It is described an
      experimental burn model using rats which allows to study different degrees of
      thermal damage. The described experimental burn model is comparable, reproducible
      by other researchers, reliable in results, simple in performance and low in cost.
      With this experimental model we have evaluated effects of skin burn treatment by
      Phagobioderm in rats. This was impossible to do by means of other experimental
      burn models, because they have not given possibility to investigate precisely the
      local histological reaction caused by treatment of burns with polymer films (in
      our case Phagobioderm). In our estimation, present modification of experimental
      model will be very useful and makes it possible to extend animal experimentation
      in the field of burns to units, which are not specialized and have only limited
      resources.

PMID- 15988086
TI  - [Differential description of heart rate regulatory mechanisms of young men at
      sensory-motor and psychoemotional load during high frequency sound exposure].
AB  - The goal of the study was the differential description of the heart rate
      regulatory mechanisms of young men and productivity of task performance during
      sensory-motor and psychoemotional load on the background of high frequency (4000
      8000 Hz) sound exposure. Analysis of statistical and spectral components of the
      heart rate variability was done for description of heart rate regulatory
      mechanisms. Sensory-motor and psychoemotional load was studied with Landolt
      rings. The study was a community trial and performed by single blind method, on
      volunteer young men (age 18-22, n=22). From the results of the study it may be
      concluded that during high frequency sound exposure, quality of sensory-motor and
      psychoemotional task performance deteriorates. In individuals with initial
      domination of sympathetic part of vegetative nervous system during high frequency
      sound exposure and sensory-motor load, sympathetic domination decreases, but
      during complex tasks of identification and selection, initially dominant
      sympathetic effects on heart increases, which creates starting conditions for
      regulatory mechanisms overload mode.

PMID- 15988085
TI  - [Diagnostic and prognostic value of the oncoprotein her-2/neu in the breast
      cancer tissue].
AB  - 49 breast cancer tissues were investigated by imunnohistochemical method, to
      reveal the expression and distribution of the oncoprotein HER-2/neu. It was
      found, that expression of the oncoprotein HER-2/neu in the tumor tissues is very
      variable, which depends on the cancer histogenesis, histological form,
      differentiation and stage of tumor development. Intensity of expression of the
      oncoprotein HER-2/neu is higher in the ductal forms of the cancer, there is
      reciprocal relationship between the intensity of the expression of the
      oncoprotein HER-2/neu and steroid hormones. Using these data we can define
      histogenesis, rate of maturation and other tumor features in more objective
      manner. This is very important for selection of the breast cancer treatment
      methods.

PMID- 15988087
TI  - [Role of NO and several mechanisms of plaferon lb action in the regulation of
      arterial blood pressure during hemorrhagic shock].
AB  - The present study aimed to establish the role of NO and mechanisms of plaferon LB
      (PLB) (USA patent N WO 02/12444 A2) effectiveness in the regulation of arterial
      blood pressure (ABP) during hemorrhagic shock (HS). As it follows from the
      results of our study and literary data analysis, stress-hormone mediated receptor
      induced accumulation of Ca2+ ions in vascular cells occurs during experimental
      HS. At that, rapid release of large amount of NO due to Ca-dependent eNOS
      activation in endothelium results in the prevalence of NO-dependent relaxation
      mechanisms over Ca2+-dependent constriction in smooth muscle cells with
      subsequent abrupt decrease in ABP. In experimental HS, reproduced against
      preliminary administration of isoptine, blockage of Ca entry in endothelial cells
      prevents intensification of Ca-dependent synthesis of nitric oxide, and
      consequently, prevents activation of NO-dependent mechanisms of dilatation
      thereby facilitating ABP elevation. Preliminary administration of LNAME inhibits
      nitric oxide synthesis in blood vessel endothelium and consequently prevents
      activation of NO-dependent mechanisms of dilatation. Insignificant (by 17%)
      increase of Ca2+ levels in artery of animals of this experimental group is likely
      due to transitory hormone-induced entry of calcium through slow Ca channels,
      which at the inhibition of NO-dependent vasodilatation provides constriction of
      blood vessels and normalization of ABP. Given the ability of PLB to regulate
      nitric oxide synthesis at various pathological processes, we suggest that
      normalization of ABP by this preparation during HS is mainly due to NO-modulating
      activity of PLB. PLB maintains physiological concentrations of NO in blood
      vessels. Nitric oxide, in its turn, provides normalization of ABP in experimental
      animals due to the regulation of vascular smooth muscle tone through the
      modulation of Ca2+ levels. Thus, we can conclude that nitric oxide plays
      significant role in the regulation of the balance between constrictory and
      dilatatory mechanisms of vascular tone. PLB due to its NO modulating activity
      provides maintenance of physiological activity of nitric oxide, normalization of
      Ca2+ levels and ABP in blood vessels.

PMID- 15988088
TI  - [The role of oxidative metabolism disturbance in the development of NO-related
      endothelial dysfunction during chronic hearth failure].
AB  - The aim of the work was to establish the oxidative metabolism changes and NO data
      in Chronic Hearth Failure (HF). 52 patients were included in the investigation,
      among them 37 patients with CHD and chronic HF (II-IV functional class by NIHA)
      and 17 without it (control group). For revealing of organism redox-status
      (ceruloplasmine, Fe3+-transfferine, Mn2+, methemoglobine) the blood paramagnetic
      centers was studied by electron paramagnetic resonance method. For revealing of
      blood free NO, the diethyldithiocarbamat (SIGMA) was used. In chronic HF the
      oxidative process intensification and organism compensate reaction reduction with
      low Fe3+-transferine levels, increased Mn2++, methaemoglobin and inactivation of
      erythrocytes membranes adrenergic receptors were revealed. In chronic HF the
      accumulation of reactive oxygen levels provoke NO transformation in peroxynitrote
      with following decreases of blood free NO and develop the endothelial
      dysfunction.

PMID- 15988089
TI  - [Mechanosensoric homeostatic function of the stomach].
AB  - Using original experimental method (partial, different extent emptying of stomach
      from contents in various parts of time after satiety condition--denying the food
      intake) the mechanosensoric, homeostatic function of the stomach was revealed
      while performing the chronic experiments on adult male dogs, while on puppies the
      ageing peculiarities of its formation was shown. On polyfistuled (stomach,
      proximal and distal parts of duodenum) adult dogs, it was demonstrated that
      duodenum participates in maintenance and formation of satiety only while complex
      irritation by chime of the interoreceptors of gastrointestinal tract in natural
      succession of digestion takes place together with the sensoric processes in
      stomach.

PMID- 15988092
TI  - [The characteristic state of health of ammonia nitrate producing workers].
AB  - The workers producing ammonia nitrate have professional contact with ammonia
      nitrate aerosol and nitrogenous gases. The state of health of ammonia producing
      workers has been examined. The morbidity, the therapeutic, neurological and
      laryngeal status have been inspected. Electrocardiography and examination by peak
      flow meter by Wotchall has been conducted. Peripheral blood test and radiography
      of backbone has been carried out as been required. It has been estimated that the
      illnesses of respiratory apparatus and musculoskeletal system predominate in the
      morbidity structure. The clinical examination of the workers with basic
      professions of the production of ammonia nitrate shows the frequent cases of
      chronic bronchitis and radiculoneuropathy. The results of function study show the
      damage of airways, the myocardiodystrophy and the changes of T wave. The nitrogen
      containing particulate pollutants that irritate respiratory systems and hard
      manual labor at these working places determine these illnesses. This fact
      corresponds with the hygiene and sanitary conditions of labor at major working
      places of production. This confirms the major role of occupational-productional
      factors in the etiology of these pathological conditions. In order to prevent the
      remote structural lesion of respiratory and cardiovascular systems it is required
      to amend the functional damage. On the basis of carefully performed study a
      complex of recreation measures has been carried out in order to improve the
      service conditions.

PMID- 15988090
TI  - [Antinecrotic and antiischemic effect of mexidol and trental in ischemia of the
      skin graft].
AB  - Antinecrotic activity of 2-ethyl-6-methyl-3 oxipyridin succinate (mexidol) and
      pentoxifylline (trental) was investigated on 32 mail rats with average body
      weight of 170-220 g. Under the influence of mexidol and trental, which were
      injected 15 min before the insection of skin graft and then once per day during 3
      days, necrotized area of skin graft is reduced by 22 and 15%, the amount of lost
      keranocytes--by 33 and 30%. In skin graft homogenates under the influence of
      mexidol rises the reduced under ischemia succinate dehydrogenase activity, while
      under trental influence it does not change. Under the influence of mexidol and
      trental on third day content of ATP rises by 29,5 and 19,5 %, ADP increases and
      decreases by 27%, creatinphosphate--by 33 and 21% correspondingly. Trentale
      improves elasticity of erythrocytes. It is suggested, that positive effect of
      mexidol on skin graft is conditioned by its ability to activate succinate
      dependent detour in oxygen phosphorilation chain of mitochondries and to raise
      content of ubiquinone, whereas the effect of trental relates with intensification
      of microcirculation, delivery of oxygen on periphery. That allows recommending
      combined use of preparations in ischemia of skin.

PMID- 15988091
TI  - [Changes of ultrastructure and p-53 protein expression on the peripheral blood
      lymphocytes of patients with vulgar form of psoriasis after balneal therapy in
      resort "nunisi"].
AB  - Analysis of peripheral blood lymphocytes ultrastructure and P-53 apoptotic
      protein expression in patients with psoriasis before and after balneal therapy in
      "Nunisi" has been performed. Samples of peripheral blood of 10 patients (22-46
      years of age) with vulgar form of psoriasis (4--disseminated form, 6--focal) were
      investigated. Duration of illness--from 2 to 24 years, remission--6-12 months.
      Balneal bath therapy in "Nunisi" included the course of 15-18 procedures, t
      degrees--36-37 degrees. Total number of patients under our observation was 65, 25
      of them received basic therapy, 40--balneal therapy. 25 persons were practically
      healthy, 5 of them were blood donors. Cells of lymphoid population from
      peripheral blood were investigated by electron microscopy and
      immunohistochemistry using of P-53 protein's marker ("Novo Castra") visualized by
      system "DAB". Character of P-53 preapoptotic protein expression and changes in
      lymphocytes ultrastructure testify to the trend of lymphocytes necrosis and
      apoptosis development especially in large granular lymphocytes during basic
      therapy. After the course of balneal therapy in "Nunisi", large granular
      lymphocytes, with signs of protein synthetic activity, as well as the psoriatic
      lesion foci in epidermis were reduced.

PMID- 15988094
TI  - Correlates of tobacco-use pattern amongst adolescents in two schools of New
      Delhi, India.
AB  - BACKGROUND: As adolescent tobacco use has been found to be a major predictor of
      future use, preventive efforts need to be focused on this section of population.
      OBJECTIVES: To assess the role of knowledge regarding tobacco, risk-taking
      attitude, peers, and other influencers on tobacco and areca nut use, amongst
      adolescents. SETTINGS AND DESIGN: A school-based cross-sectional study covering
      two schools. Students of classes IX and XI, of selected schools, participated in
      the study (n = 596). METHODS: A pretested and validated, close ended, self
      administered questionnaire was used. Sociodemographic factors, awareness
      regarding tobacco, risk-taking attitudes, role of peers and other influencers,
      and tobacco, areca nut and alcohol use, were studied. STATISTICAL ANALYSIS: Point
      estimates, 98% Confidence Intervals, tests of significance, bivariate and
      multivariate analysis (multiple logistic regression). RESULTS: Almost 42% of
      tobacco users started before the age of 12 years. Peer pressure, general stress,
      and media were important influencers. Logistic regression analysis showed that
      students in public school were using more tobacco [Odds ratio (OR) = 1.85, P =
      0.174] and tobacco/areca nut (OR = 1.14, P = 0.02). The difference in use between
      the genders and class in which studying was statistically not significant. Lesser
      proportion of those possessing adequate knowledge regarding tobacco used it as
      compared to those without adequate knowledge (OR = 0.13, P < 0.001) however,
      possession of adequate knowledge was not a good predictor of areca nut
      consumption (OR = 0.86, P = 0.585). The most important correlate for tobacco use
      (OR = 6.41, P < 0.001) and areca nut use (OR = 11.17, P < 0.001) was risk-taking
      attitude. CONCLUSION: Multi-pronged and concerted efforts targeting children at
      an early age are required to prevent tobacco and areca nut use among adolescents.

PMID- 15988093
TI  - Survivin protein expression positively correlated with proliferative activity of
      cancer cells in bladder cancer.
AB  - CONTEXT: Survivin is an inhibitor of apoptosis that is selectively over-expressed
      in common human cancers, but not in normal tissues, and that correlates with
      aggressive disease and unfavorable outcomes. AIMS: To identify the role of
      survivin in bladder carcinogenesis and the correlation between survivin protein
      expression and the occurrence of spontaneous apoptosis, proliferative activity of
      cancer cells. SETTINGS AND DESIGN: Retrospective analysis. METHODS AND MATERIAL:
      Bladder transitional cell cancer (BTCC) tissue samples for 128 patients were
      investigated, with normal bladder tissues serving as controls. From these tumor
      samples, 42 (32.8%) were grade I, 59 (46.1%) were grade II, and 27 (21.1%) were
      grade III; 72 (56.2%) were superficial, 56 (43.8%) were invasive. The survivin
      protein level was quantified by Western blot analysis. The apoptotic index (AI)
      using in situ labeling apoptotic DNA fragment kit and the Ki-67 labeling index
      (Ki-67LI) with an anti-Ki-67 monoclonal antibody were analyzed in these tumors,
      respectively. STATISTICAL ANALYSIS USED: Differences in the S/beta ratio between
      tumor grade and stage were evaluated by using unpaired t-test and F-test. The
      relationships between the S/beta ratios and AIs, Ki-67LIs of tumors were
      evaluated by Pearson correlation coefficient. RESULTS: High survivin levels were
      detected by Western blot analysis in tumor tissue extracts. None of the
      expression of survivin protein was found in normal bladder tissues. Survivin
      levels were significantly different from different clinical stages and
      pathological grades of the tumors (P > 0.05, respectively). Spearman rank
      correlation test revealed a positively correlation between survivin protein level
      and the proliferative activity (P < 0.001) and failed to find significant
      correlation between AI and survivin protein level (P > 0.05). CONCLUSIONS:
      Survivin protein expression played an important role in the malignant progression
      of BTCC.

PMID- 15988095
TI  - Investigation of genetic heterogeneity in Mycobacterium tuberculosis isolates
      from tuberculosis patients using DNA fingerprinting.
AB  - BACKGROUND: DNA fingerprinting of Mycobacterium tuberculosis (MTB) based on
      IS6110 has been shown to be a powerful epidemiologic tool. Restriction enzyme
      analysis (REA) is a fingerprinting technique, which is used for differentiation
      and investigation of genetic diversity among mycobacterial species. AIMS: To
      investigating the genetic heterogeneity in MTB isolates in Ahvaz, Iran. SETTINGS
      AND DESIGN: It was a cross-sectional study conducted in Ahvaz, Iran. METHODS AND
      MATERIAL: One hundred and eighty clinical isolates of MTB were collected from TB
      reference unit, PHLS, Ahvaz, Iran. The PCR-REA employed uses a simple DNA
      extraction followed by a PCR step involving a single primer based on the
      insertion sequence IS6110. Restriction enzyme analysis was performed on the
      amplification products using HaeIII enzyme. STATISTICAL ANALYSIS: Data was
      analyzed using SPSS software and chi-square test/Fishers' exact test was applied
      wherever applicable. RESULTS: The isolates were divided into four clusters based
      on their REA patterns. Cluster I contained 71.1% of strains with two fragments of
      72 and 118. Cluster II with three fragments of 72, 118, and 194; cluster III with
      three fragments of 118, 194, and 234; and cluster IV with four fragments of 72,
      118, 194, and 234 base pairs. As many as 73.8% of the identical fingerprint
      patterns were seen in male patients. Accounting the men as the major population
      in the study, there was no significant difference between REA patterns and sex;
      similarly, with age, patients' occupation and degree of smear positivity.
      However, we found significant correlation between REA patterns and patients'
      origin. As many as 61.6% of identical patterns were found in the patients who
      were lived in the same suburb. CONCLUSIONS: By PCR-based REA typing, the isolates
      studied were grouped into four clusters each containing between two and four
      fragments. However, in order to ascertain the level of heterogeneity of MTB
      isolates in their sample, further testing with a more discriminatory method is
      needed.

PMID- 15988096
TI  - Transphyseal spread of benign tumors and infections in pediatric patients: a
      series of six cases.
AB  - Epiphyseal extension of benign pathology is regarded as an infrequent occurrence.
      This observation has been attributed to anatomical and biochemical phenomenon
      unique to physeal cartilage. We report a retrospective series of six patients
      over a period of 4 years, diagnosed with benign pathologies that showed crossing
      of an open physeal plate by the disease. Four of these cases were infections and
      two were benign tumors. The patients were aged between 5 and 11 years, all of
      them were treated at a tertiary referral centre and followed up for a minimum
      period of 6 months to evaluate the progress of disease. The findings are more
      than just a pathological curiosity as they alter the management and surgical
      procedure that needs to be performed for these conditions. The recognition of the
      fact that benign tumors may occasionally present with transphyseal spread will
      prevent unjustified radical procedures that are best reserved for aggressive
      malignant conditions.

PMID- 15988097
TI  - Vesicocutaneous fistula arising from a bladder diverticulum.
AB  - A 55-year-old man presented with intermittent episodes of urinary leak through
      the left groin following an abscess drainage at that site at the age of 5 years.
      Since then he had been suffering from recurrent urinary tract infections and
      urinary leak, which used to be treated symptomatically. Intravenous urogram
      (IVU), voiding cystourethrogram (VCU), and cystoscopy done in our institution
      revealed a bladder diverticulum with a stone in situ, which was communicating
      with the fistulous opening located in the left groin. Diverticulectomy and
      excision of the fistulous tract cured the patient. A long-standing fistula
      arising from a bladder diverticulum at relatively distant site is of extreme
      rarity. Vesicocutaneous fistula from an iatrogenic injury to vesical diverticulum
      resulting from a groin surgery has not been reported so far.

PMID- 15988098
TI  - Idiopathic mediastinal fibrosis presenting as mediastinal compression syndrome.
AB  - Mediastinal compression syndrome is a commonly seen entity. Mediastinal
      compression, mostly due to a space-occupying lesion, is distinct and different
      from mediastinitis/mediastinal fibrosis, which could also lead to superior vena
      cava syndrome. Idiopathic mediastinal fibrosis should also be considered as
      differential diagnosis of mediastinal structures with various radiological, CT
      and MRI and histological features if feasible. Medical therapy is disappointing
      while surgical cure has limitations. This interesting patient presented as
      mediastinal compression syndrome, which on investigation was postulated as
      idiopathic mediastinal fibrosis, as a diagnosis on exclusion of other causes,
      which is rare, hence is being reported.

PMID- 15988099
TI  - Tuberculosis of urinary bladder presenting as pseudoureterocele.

PMID- 15988100
TI  - Morbidity of Myocardial Infarction Multicenter Study in Japan (3M Study): study
      design and event rates for myocardial infarction and coronary death by age
      category in Japanese workers.
AB  - BACKGROUND: Although there have been regional studies, there has not been a
      detailed nationwide investigation of the morbidity from acute myocardial
      infarction (MI) in Japanese workers. METHODS AND RESULTS: Registration of MI and
      sudden death was done by full-time occupational physicians in Japan. Among
      133,099 workers (109,550 men, 23,549 women) from 41 workplaces (April 1994 to
      March 1997) and 257,440 workers (207,310 men, 50,130 women) from 76 workplaces
      (April 1997 to March 2000), 297 fatal and nonfatal cardiac events were
      registered. The definitions of MI and coronary death followed the criteria of the
      WHO MONICA Project. The event rate in men rose sharply around the age of 45
      years. Using definition 1 (fatal definite + fatal possible + fatal unclassifiable
      + nonfatal definite), the age-standardized annual event rate and case fatality
      rate for men aged 35-64 years was 40.2 per 100,000 persons and 22.2%,
      respectively. These figures were significantly lower compared with those from
      Western reports and were also lower than previously reported for Japanese
      communities. CONCLUSION: The Morbidity of Myocardial Infarction Multicenter Study
      in Japan revealed a surprisingly low incidence of coronary events, which may be
      attributable to prevention and early treatment of coronary risk factors among
      company workers in Japan.

PMID- 15988101
TI  - Impact of the revised criteria for acute myocardial infarction using cardiac
      troponins in a Japanese population with acute coronary syndromes.
AB  - BACKGROUND: The clinical implications of applying the new criteria of acute
      myocardial infarction (AMI) with cardiac troponins in terms of their diagnostic
      and prognostic impact in patients with suspected acute coronary syndromes (ACS)
      have not been well evaluated. METHODS AND RESULTS: The study group comprised 973
      consecutive patients who were diagnosed as having ACS with or without ST
      elevation (STE). They were divided into 3 groups: unstable angina (UA) group
      (n=195) representing patients with no significant elevations of creatine kinase
      (CK) and troponin T (TnT); TnT-myocardial infarction (MI) group (n=170) with TnT
      elevation and no CK elevation (additionally detected AMI by the new criteria); CK
      MI group (n=608) with significant elevation of CK (AMI by the old criteria). In
      the TnT-MI group, 140 (76%) patients had non-STE ACS. In-hospital mortality rates
      for STE ACS were 0%, 2.5% and 9.7% in the UA, TnT-MI and CK-MI groups,
      respectively. The corresponding values for non-STE ACS were 1.8%, 4.6%, and
      16.5%, respectively (p<0.0001), suggesting a pivotal role of TnT. In multiple
      logistic regression analysis, significant CK elevation was selected as an
      independent predictor of in-hospital death in concurrence with age > or =75
      years, prior MI, shock and low left ventricular ejection fraction in non-STE ACS.
      CONCLUSIONS: The new criteria result in a substantial increase in the diagnosis
      of AMI from non-STE ACS in particular. They assist greatly in detailed risk
      stratification of ACS patients, notably in cooperation with the old CK criteria.

PMID- 15988103
TI  - Novel index of coronary collateral development as a useful predictor of clinical
      outcome in type 2 diabetic patients with coronary artery disease.
AB  - BACKGROUND: There is a paucity of information regarding the impact of the
      coronary collaterals on prognosis in type 2 diabetic (T2DM) patients. We
      developed a novel index, which considers not only the degree of collateral
      circulation but also the stimulus of collateral development, and investigated its
      prognostic value in T2DM patients with coronary artery disease (CAD). METHODS AND
      RESULTS: One hundred and ninety four consecutive T2DM patients were analyzed and
      followed for an average of 30 months. We measured the diameter stenosis (DS; %),
      corrected TIMI frame count (CTFC) and Rentrop score at 3 major epicardial
      coronary arteries. The collateral development (CD) score was calculated by:
      (Sigma Rentrop score +1)/Sigma [DS (%) x CTFC] x1,000. During the follow-up,
      acute cardiovascular events occurred in 49 patients. By multivariate analysis,
      the CD score was an independent predictor of adverse events not only in the total
      population (p<0.001), but in all 3 subgroups (p=0.020 for coronary artery bypass
      grafting, p=0.030 for percutaneous transluminal coronary angioplasty (PTCA) and
      p=0.003 for the medical group). Furthermore, patients in the tertile with the
      highest CD score showed improved survival by Kaplan-Meier analysis in the total
      population, the PTCA and the medical group. CONCLUSIONS: The CD score, a novel
      index of collateral development, may be a useful predictor of clinical outcome in
      T2DM patients with CAD.

PMID- 15988102
TI  - Randomized comparison of cilostazol vs ticlopidine for antiplatelet therapy after
      coronary stenting.
AB  - BACKGROUND: Cilostazol and ticlopidine are commonly prescribed for prevention of
      thrombosis after coronary stenting, but few studies have compared them. METHODS
      AND RESULTS: In the present study 642 patients who underwent stenting were
      randomized to treatment either with cilostazol + aspirin (C group, 321 patients)
      or ticlopidine + aspirin (T group, 321 patients). Quantitative coronary
      angiography (QCA) was performed immediately after stenting and at the 6-month
      follow-up. Treatment was continued until follow-up angiography. Baseline patient
      characteristics did not differ significantly. With the exception of a higher rate
      of stenting in a venous graft in the C group, there were no differences in
      angiographic characteristics or stent type. Baseline QCA analysis of the
      reference diameter, minimal lumen diameter (MLD) showed no significant
      differences. Follow-up QCA analysis of the MLD showed no significant differences.
      There were also no differences in restenosis or target lesion revascularization
      rates, or in the incidence of adverse reactions. However, the rate of subacute
      thrombosis (SAT) was significantly higher in the C group than in the T group (2%
      vs 0.3%, p=0.02). CONCLUSION: In the present study there was a similar restenosis
      rate with cilostazol or ticlopidine, but the rate of SAT was significantly higher
      with cilostazol. There was no significant difference in adverse reactions.

PMID- 15988104
TI  - Polymorphism of the 3'-untranslated region of interleukin-12 p40 gene is not
      associated with the presence or severity of coronary artery disease.
AB  - BACKGROUND: Interleukin (IL)-12 is thought to play an important role in the
      development of atherosclerosis and recently, polymorphism of the 3'-untranslated
      region of the IL-12 p40 gene (A1188C) was reported to be associated with diabetes
      and multiple sclerosis. However, the association between this genetic
      polymorphism and coronary artery disease (CAD) has not been studied. METHODS AND
      RESULTS: The frequency of this polymorphism was investigated in 555 patients
      undergoing coronary angiography: 395 had CAD, of whom 161 also had a myocardial
      infarction (MI). With regard to the IL-12 p40 polymorphism, 125 had the A/A, 268
      had the A/C, and 162 had the C/C genotype. The prevalence of CAD did not differ
      among the groups (71%, 73%, and 69%, respectively; p= NS). The prevalence of MI
      was also similar among the groups (28%, 27%, and 33%, respectively; p= NS).
      Moreover, the number of >50% stenotic vessels, >50% stenotic segments, and < or
      =50% stenotic segments did not differ among the 3 groups. CONCLUSIONS:
      Polymorphism of IL-12 p40 gene was not found to be associated with the presence
      or severity of CAD, suggesting that it does not play an important role in the
      development of this disease.

PMID- 15988105
TI  - Abnormal ankle brachial indices may predict cardiovascular disease among diabetic
      patients without known heart disease.
AB  - BACKGROUND: Cardiovascular disease remains the primary cause of diabetes
      associated morbidity and mortality. Previous studies have failed to provide
      accurate, inexpensive, screening techniques to detect cardiovascular disease in
      diabetics. Ankle brachial indices (ABI) testing may be an effective screening
      technique for diabetics. METHODS AND RESULTS: The aim of this 100-subject
      clinical study was to determine cardiovascular disease prevalence, via perfusion
      stress testing, in diabetic patients having abnormal ABI (<0.90) and without
      known heart disease who were referred to the South Carolina Heart Center,
      Columbia, SC for nuclear perfusion stress testing. Study data were analyzed using
      frequency and descriptive statistics and 2-sample T-testing. Mean subject age was
      62+/-11 years, ABI 0.76+/-13, and ejection fraction 60+/-12%. Perfusion stress
      testing detected 49 abnormal electrocardiograms, 36 subjects with coronary
      ischemia, 20 with diminished left ventricular function, and 26 subjects having
      significant thinning of the myocardium. There were 71 subjects who tested
      positive for at least one form of cardiovascular disease. The sole predictive
      variable reaching significance for the presence of cardiovascular disease was an
      ABI score <0.90 (p< or =0.0001). CONCLUSION: Cardiovascular disease may be
      predicted among diabetic patients via ABI scores and confirmed by nuclear
      perfusion testing.

PMID- 15988106
TI  - Assessing muscle vasodilation using near-infrared spectroscopy in cardiac
      patients.
AB  - BACKGROUND: In patients with chronic heart failure, an inadequate increase in
      muscle blood flow resulting from impaired vasodilation plays a key role in their
      exercise intolerance. However, no non-invasive methods to assess muscle
      vasodilation during dynamic exercise were available. We investigated whether the
      changes in tissue hemoglobin and myoglobin content (total-Hb + Mb) determined by
      non-invasive measurement using near-infrared spectroscopy (NIRS) reflect vessel
      conductance of working muscle during exercise. METHODS AND RESULTS: Sixteen
      patients (10 patients with normal cardiac systolic function, 6 with cardiac
      dysfunction) performed incremental bicycle exercise testing. Total-Hb + Mb from
      the right vastus lateralis muscle was monitored using NIRS. Leg blood flow (LBF)
      in the right femoral vein was measured using a thermodilution technique every 30
      60 s. Leg vessel conductance was calculated as LBF/mean arterial pressure at each
      time of the measurement. In all cases except 1, the levels of total-Hb + Mb
      showed significant correlation with the leg vessel conductance (r=0.792 to
      0.980). Intra-subject reproducibility of the NIRS measurement was also confirmed
      in 6 patients. CONCLUSIONS: Total-Hb + Mb from NIRS reflected muscle vasodilation
      during sub-maximal dynamic exercise in patients with and without cardiac
      dysfunction, indicating that NIRS provides a valuable method to assess the
      working muscle vasodilation.

PMID- 15988107
TI  - Brachial -- ankle pulse wave velocity is a simple and independent predictor of
      prognosis in patients with acute coronary syndrome.
AB  - BACKGROUND: Although a very simple method of measuring brachial -- ankle pulse
      wave velocity (baPWV) has become available in a clinical setting, whether baPWV
      can predict future cardiovascular events remains uncertain. We examined whether
      baPWV is a predictor of cardiovascular events in patients with acute coronary
      syndrome (ACS). METHODS AND RESULTS: baPWV measurement was performed in 215
      consecutive patients with ACS. During the follow-up period (26+/-10 months), 46
      patients experienced post-hospitalization cardiovascular events (18 patients
      experienced a major event (eg, stroke, re-admission for heart failure or cardiac
      death), and 28 patients experienced coronary re-intervention). A receiver
      operating characteristic curve demonstrated that the best cut-off point of a
      baPWV for predicting a post-hospitalization cardiovascular event was 17.00 m/s
      and that for predicting a major cardiovascular event was 18.00 m/s. After the
      adjustment for the conventional risk factors influencing the prognosis, a
      multivariate Cox proportional hazards model demonstrated that both cut-off points
      of baPWV had a significant hazard ratio for a post-hospitalization event: 5.47
      (2.69-11.09) and for a major cardiovascular event: 9.22 (2.78-30.56).
      CONCLUSIONS: baPWV is a simple predictor of the prognosis of patients with ACS
      that is independent of conventional risk factors for ACS.

PMID- 15988108
TI  - Paroxysmal atrial fibrillation coincident with cardiac decompensation is a
      predictor of poor prognosis in chronic heart failure.
AB  - BACKGROUND: The prognostic significance of atrial fibrillation (AF) in chronic
      heart failure (CHF) remains poorly understood. METHODS AND RESULTS: Death and
      rehospitalizaion for CHF exacerbation for 427 consecutive patients hospitalized
      from 1996 to 2002 were retrospectively analyzed in relation to cardiac rhythm:
      sinus rhythm (SR; n=239) or AF (n=188). The AF group was classified according to
      an Intervention (n=57) or Non-Intervention (n=131) group for defibrillating AF.
      During the follow-up of 34+/-23 months, there was no significant difference of
      mortality or morbidity between the SR and AF groups, or between the Intervention
      and Non-Intervention groups, respectively. However, the Non-Intervention group
      consisted of 28 patients with paroxysmal AF (PAF), which spontaneously converted
      to SR during hospitalization, and 103 with chronic AF (CAF). The
      rehospitalization for CHF exacerbation was significantly higher in PAF than that
      in CAF and SR (p=0.00005 and 0.002, respectively). Multivariate Cox analysis
      demonstrated that, PAF, but not CAF, was a predictor of readmission (relative
      risk 2.30, p=0.004, 95% confidence interval 1.30 to 4.05). CONCLUSIONS: The
      present data implied that PAF coincident with cardiac decompensation could be a
      new predictor of prognosis for CHF. The management strategies of AF in CHF should
      be discussed according to the phenotype of AF.

PMID- 15988109
TI  - Beneficial effects of biatrial pacing on cardiac function in patients with
      bradycardia -- tachycardia syndrome.
AB  - BACKGROUND: Biatrial (BiA) pacing prevents atrial fibrillation. By an unknown
      mechanism. The purpose of this study was to use Doppler echocardiography to
      evaluate the hemodynamic effects during BiA pacing. METHODS AND RESULTS: The
      subjects were 7 patients with bradycardia - tachycardia syndrome with an
      implanted pacemaker. Atrial pacing sites were the right atrial appendage (RAA)
      and coronary sinus. P wave duration during BiA pacing (123 +/-16 ms) was
      significantly shorter than during either RAA pacing (167+/-19 ms, p<0.05) or
      sinus rhythm (148+/-12 ms, p<0.05). Doppler echocardiography revealed a greater
      cardiac output during BiA pacing than during RAA pacing (4.1+/-1.1 vs 3.5+/-0.7
      L/min, p=0.042). The Doppler waveform of transmitral flow indicated that the left
      ventricular contraction interrupted the atrial filling wave during RAA pacing.
      The interval between the end of the atrial filling wave of transmitral flow and
      the mitral valvular closing sound was significantly increased by BiA pacing
      compared with RAA pacing (56+/-65 vs 40+/-57 ms, p=0.047). CONCLUSION: Cardiac
      hemodynamics were improved by BiA pacing and reduction of left atrial load may be
      one of the mechanisms.

PMID- 15988110
TI  - Catheter ablation of tachycardias after undergoing a surgical atriotomy using a
      multipolar electrode catheter: conventional mapping method without an
      electroanatomical mapping system.
AB  - BACKGROUND: A variety of supraventricular tachyarrhythmias may occur in patients
      after undergoing a surgical atriotomy. The purpose of this study was to
      characterize them and determine the role of conventional mapping. METHODS AND
      RESULTS: In 45 patients after a surgical atriotomy, 68 atrial tachyarrhythmias
      were observed. A conventional mapping system with a 20-pole electrode catheter
      used in the electrophysiological study detected 39 atrial tachycardias (ATs).
      Type 1 atrial flutter (AFL) was observed in 23 and reverse type 1 AFL in 4. AT
      was classified into 3 subgroups, namely, incisional macroreentrant AT (n=31),
      incisional focal AT (n=1) and non-incisional AT (n=7). In the patients with
      incisional macroreentrant AT after the standard right atriotomy, the 20-pole
      electrode catheter placed on the incision could easily record the entire sequence
      of the atrial activation. Successful catheter ablation was achieved in all
      patients with incisional reentrant AT. The ablation site of incisional reentrant
      AT was the isthmus between the incision and the superior vena cava cannulation
      scar in 4, between the incision and the inferior vena cava cannulation scar in
      22, and the area at the septal incision in 3. The remaining 2 incisional ATs were
      left atrial AT and right atrial transincisional AT. CONCLUSIONS: The conventional
      mapping system is still very useful for making an electrophysiological diagnosis
      in patients after a standard right atriotomy.

PMID- 15988111
TI  - Valve dysfunction of the cloth-covered Starr-Edwards ball valve.
AB  - BACKGROUND: Between June 1968 and March 1977, Starr-Edwards cloth-covered ball
      valves were used for valve replacement on a routine basis. METHODS AND RESULTS:
      Among the 66 operative survivors who underwent an isolated aortic or mitral valve
      replacement, 20 patients required reoperation 22 times because of valve
      dysfunction, thromboembolic complication, paravalvular leakage, hemolytic anemia,
      and/or prosthetic valve endocarditis. Reoperation was performed at a mean of
      15.9+/-9.8 years after initial replacement. Excised valves were examined and
      reoperation after initial operation was reviewed. Operative mortality was 10.0%.
      Freedom from reoperation for aortic valve replacement and mitral valve
      replacement was 56.2% at 34 years and 61.0% at 37 years after initial operation,
      respectively. Cloth wear or pannus formation were observed in all excised
      prostheses. Orifice cloth was more markedly worn in mitral valves than in aortic
      valves, particularly in mitral valves of more than 20 years old. Pannus
      overgrowth contributed to valve regurgitation in the older valves. CONCLUSIONS:
      Early diagnosis of valve dysfunction and reoperation are recommended as soon as
      symptoms appear.

PMID- 15988112
TI  - Bone marrow cell-seeded biodegradable polymeric scaffold enhances angiogenesis
      and improves function of the infarcted heart.
AB  - BACKGROUND: The present study examined whether a bioengineered polyglycolic acid
      cloth (PGAC) impregnated with bone marrow cells (BMC) improved the function and
      angiogenesis of the infarcted heart. METHODS AND RESULTS: The coronary artery was
      ligated in Lewis rats and the infarcted area was covered with a PGAC in group 1
      (n=8), with a PGAC containing basic-fibroblast growth factor (b-FGF) in group 2
      (n=11) and a PGAC containing b-FGF and freshly isolated BMC in group 3 (n=10). In
      addition, BMC derived from transgenic mice expressing green fluorescent protein
      (GFP)-BMC were seeded into a PGAC, which was sutured over the infarcted area of
      C57BL/6 mice (n=5). In the rat study, developed and systolic pressures, dp/dt max
      and dp/dt min) were the highest in group 3, as were the capillary density in the
      PGAC and infarcted area. In the mouse study, there were few GFP-BMC in the PGAC,
      but none in the infarcted area. CONCLUSIONS: A PGAC with BMC improved cardiac
      function by inducing angiogenesis without migration of BMC. Freshly isolated BMC
      work as angiogenic inducers and a PGAC is useful as a "drug delivery system".

PMID- 15988113
TI  - Pilsicainide-induced coronary vasospasm in a patient with Brugada-type
      electrocardiogram.
AB  - A 65-year-old man with Brugada-type electrocardiogram (ECG) was admitted to our
      hospital for chest pain, palpitation and faintness. In the cardiac
      electrophysiological study, no ventricular tachyarrthymia was induced either at
      baseline or after pilsicainide (50 mg) infusion. Intravenous administration of
      pilsicainide exaggerated ST-segment elevation in V(1-4) and converted it to the
      coved type in V(1), accompanied by severe chest pain. Coronary angiography
      revealed the vasospasm of the right coronary artery was induced by pilsicainide,
      not by ergonovine. This is the first case report of coronary vasospasm induced by
      a pure sodium channel blocker in a patient with Brugada-type ECG.

PMID- 15988114
TI  - Reoperation for ascending aortic aneurysm, coronary ostial aneurysm and patent
      Cabrol trick after bentall operation for aortitis syndrome.
AB  - A 38-year-old woman who had undergone an original Bentall operation in December
      1995 for annuloaortic ectasia associated with ulcerative colitis required
      reoperation for ascending aortic aneurysm, coronary ostial aneurysm, and patent
      Cabrol trick. The initial Bentall operation included aortic root replacement
      using a valved conduit and reconstruction of the coronary arteries. Both coronary
      ostia were directly anastomosed to the composite valved graft, which was wrapped
      with the dilated aortic wall, and a Cabrol trick was added at the same time. She
      underwent reoperation for a 60 mm ascending aortic aneurysm which had been used
      for wrapping at the initial operation. The findings at reoperation were a patent
      Cabrol trick, leakage from the distal anastomosis, aneurysm of both coronary
      ostia, and paravalvular leakage. The repairs included graft replacement, leaving
      the valvular prosthesis, reconstruction of both coronary arteries by the Piehler
      method and Carrel patch technique, repair of the paravalvular leakage, and
      closure of the Cabrol trick. Her postoperative course was uneventful, and the
      serum concentration of C-reactive protein remained within normal limits. Strict
      follow-up care is required to avoid further anastomotic dehiscence.

PMID- 15988115
TI  - Idiopathic premature ventricular contractions arising from the pulmonary artery:
      importance of mapping in the pulmonary artery in left bundle branch block-shaped
      ventricular arrhythmias.
AB  - A patient underwent radiofrequency (RF) catheter ablation of symptomatic
      idiopathic ventricular contractions (PVCs). RF energy applications at 2 sites in
      the right ventricular outflow tract (RVOT), where both the earliest ventricular
      activation and near-perfect pace mapping were obtained, did not abolish the PVC
      but resulted in changes in the QRS morphology of the PVC. Complete elimination of
      the PVC was achieved with RF energy application at a site within the pulmonary
      artery 13 mm above the pulmonary valve, which was greater than 20 mm away from
      the failed ablation sites within the RVOT.

PMID- 15988116
TI  - Two adults requiring implantable defibrillators because of ventricular
      tachycardia and left ventricular dysfunction caused by presumed Kawasaki disease.
AB  - There is an adult patient population in Japan with undiagnosed coronary artery
      lesions caused by Kawasaki disease (KD) occurring before 1967, the time at which
      KD was first described. Two adult patients presented with a low left ventricular
      (LV) ejection fraction and ventricular tachycardia (VT) caused by presumed KD. A
      43-year-old man with rapid VT had a history of an acute febrile illness with
      desquamation of the fingertips at the age of 10 months. Coronary angiography
      (CAG) showed segmental stenosis of the right coronary artery (RCA) and occlusion
      of the left anterior descending artery with a giant aneurysm. The other patient
      was a 48-year-old man with a history of ischemic cardiomyopathy diagnosed after a
      previous myocardial infarction when he was 32 years old. He had segmental
      stenosis of the RCA on CAG. Non-sustained VT with transient unconsciousness was
      observed during 24-h Holter electrocardiography. Rapid VT with syncope was
      induced in both patients in the electrophysiologic studies and an implantable
      defibrillator was required to prevent sudden death. Physicians must be aware that
      VT can occur in older patients with LV dysfunction many years after KD.

PMID- 15988118
TI  - Prediction of theophylline clearance in CCl4-treated rats using in vivo CYP1A2
      and CYP3A2 contents assessed with the PKCYP test.
AB  - We previously established a method to predict the drug metabolism capacity of
      injured liver based on pharmacokinetic estimation of the amount of cytochrome
      P450 (CYP) in vivo (PKCYP test), by introducing the apparent liver-to-blood free
      concentration gradient in vivo (qg) as a parameter. Here we show that the amount
      of CYP3A2 in CCl(4)-treated rats can be estimated appropriately by applying the
      PKCYP test using midazolam (MDZ) as a probe, assuming that the qg value in
      control rats does not change. We applied the results to predict the clearance of
      theophylline as a model drug with a physiologically based pharmacokinetic model.
      Male Sprague-Dawley rats were pretreated with CCl4, and the amount of CYP (A
      CYP(vivo)) was quantified by Western blotting. The qg value of MDZ was determined
      in control rats and used to estimate the amounts of CYP3A2 in CCl4-treated rats;
      the result agreed well with the observed values. The qg value of CYP3A2 estimated
      with MDZ as a probe was used together with our previously reported value for
      CYP1A2 (theophylline metabolism in the liver is known to be almost entirely
      mediated by CYP3A2 and CYP1A2) to predict the total body clearance (CL(tot)) of
      theophylline in CCl4-treated rats. The predicted CL(tot) was about one-third of
      the observed value, which was considered acceptable. The time-course of
      theophylline concentration in serum simulated with a physiologically-based
      pharmacokinetic model agreed well with the observed values. Thus, the PKCYP test
      using MDZ as a probe can be used to predict the amount of CYP3A2 and the CL(tot)
      of theophylline in CCl4-treated rats.

PMID- 15988117
TI  - Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based
      therapies.
AB  - Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole,
      esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver.
      There are genetically determined differences in the activity of this enzyme. The
      genotypes of CYP2C19 are classified into the three groups, rapid extensive
      metabolizer (RM), intermediate metabolizer (IM), and poor metabolizer (PM). The
      pharmacokinetics and pharmacodynamics of PPIs depend on CYP2C19 genotype status.
      Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are
      lowest, those in the IM group come next, and those in the PM group are highest of
      the three groups. These CYP2C19 genotype-dependent differences in
      pharmacokinetics and pharmacodynamics of PPIs influence the cure rates for the
      gastro-esophageal reflux disease and H. pylori infection by PPI-based therapies.
      For the better PPI-based treatment, doses and dosing schemes of PPIs should be
      optimized based on CYP2C19 genotype status.

PMID- 15988119
TI  - Evaluation of dextromethorphan metabolism using hepatocytes from CYP2D6 poor and
      extensive metabolizers.
AB  - It is important to estimate the defective metabolism caused by genetic
      polymorphism of drug metabolizing enzymes before the clinical stage. We evaluated
      the utility of cryopreserved human hepatocytes of CYP2D6 poor metabolizer (PM)
      for the estimation of the metabolism in PM using dextromethorphan (DEX) as the
      probe drug for CYP2D6 substrate. The results of low formations of dextrorphan
      (DXO) and 3-hydroxymorphinan (3-HM) in CYP2D6 PM hepatocytes incubated with
      dextromethorphan reflected the clinical data. Formation of 3-methoxymorphinan (3
      MEM) normalized by CYP3A4/5 activity in the PM hepatocytes reached about 2.8-fold
      higher than that in CYP2D6 extensive metabolizer (EM) hepatocytes, which clearly
      showed the compensatory metabolic pathway of O-demethylation catalyzed by CYP2D6
      as seen in clinical study. On the contrary, in the condition of the EM
      hepatocytes with CYP2D6 inhibitors, the enhancement of 3-MEM formation was not
      observed. In phase II reaction, the glucuronide formation rate of DXO in the PM
      hepatocytes was lower than that in the EM hepatocytes, which was consistent with
      clinical data of DXO-glucuronide (DXO-glu) concentration. These results would
      suggest that CYP2D6 PM hepatocytes could be a good in vitro tool for estimating
      CYP2D6 PM pharmacokinetics.

PMID- 15988120
TI  - Effect of protein binding of pilsicainide on the pharmacokinetics.
AB  - To evaluate the effect of protein binding of pilsicainide on its clearance and
      the contribution of protein binding to optimized pilsicainide therapy, clinical
      laboratory and pharmacokinetic data were studied in 160 Japanese inpatients
      (Study 1) and 18 Japanese inpatients (Study 2). To determine the relation between
      protein concentration and the protein binding ratio of pilsicainide in vitro, the
      effect of human alpha1-acid glycoprotein (AAG) and human albumin on the binding
      ratio was studied. The mean ratio of serum pilsicainide concentration to dose per
      body weight (C/D) increased with increases in the C-reactive protein (CRP)
      concentration in Study 1. The AAG level increased with increases in the CRP
      concentration and the binding ratio increases in the AAG concentration in the
      Study 2. The binding ratios increased with increased AAG and albumin
      concentrations; the AAG concentration relative to the ratio was particularly
      large in vitro study. These results suggest C/D is increased in patients with
      high CRP levels because of binding of pilsicainide to protein, resulting
      decreased clearance.

PMID- 15988121
TI  - Pharmacokinetic-pharmacodynamic analysis of antipsychotics-induced extrapyramidal
      symptoms based on receptor occupancy theory incorporating endogenous dopamine
      release.
AB  - We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical
      and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic
      (PK-PD) model based on the receptor occupancy. We collected the data for EPS
      induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a
      typical antipsychotic, haloperidol from literature and analyzed the following
      five indices of EPS, the ratio of patients obliged to take anticholinergic
      medication, the occurrence rates of plural extrapyramidal symptoms (more than one
      of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.),
      parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e.,
      a model incorporating endogenous dopamine release owing to 5-HT2A receptor
      inhibition and a model not considering the endogenous dopamine release, and used
      them to examine the relationship between the D2 receptor occupancy of endogenous
      dopamine and the extent of drug-induced EPS. The model incorporating endogenous
      dopamine release better described the relationship between the mean D2 receptor
      occupancy of endogenous dopamine and the extent of EPS than the other model, as
      assessed by the final sum of squares of residuals (final SS) and Akaike's
      Information Criteria (AIC). Furthermore, the former model could appropriately
      predict the risks of EPS induced by two other atypical antipsychotics, clozapine
      and ziprasidone, which were not incorporated into the model development. The
      developed model incorporating endogenous dopamine release owing to 5-HT2A
      receptor inhibition may be useful for the prediction of antipsychotics-induced
      EPS.

PMID- 15988122
TI  - Transcellular transport of creatinine in renal tubular epithelial cell line LLC
      PK1.
AB  - BACKGROUND/AIM: Creatinine is excreted into urine via tubular secretion in
      addition to glomerular filtration. In the present study, characteristics of the
      creatinine transport in renal epithelial cells were investigated. METHODS: The
      transcellular transport and accumulation of [14C]creatinine and
      [14C]tetraethylammonium (TEA) were assessed using LLC-PK1 cell monolayers
      cultured on porous membrane filters. RESULTS: [14C]Creatinine was transported
      directionally from the basolateral to apical side of LLC-PK1 cell monolayers.
      Basolateral uptake of [14C]creatinine was dependent on membrane potential, and
      was saturable with apparent K(m) and V(max) values of 13.2+/-2.8 mM and 13.1+/
      3.1 nmol/mg protein/5 min, respectively. Concomitant administration of organic
      cations (1 mM) such as cimetidine, quinidine and trimethoprim inhibited both the
      transcellular transport and accumulation of [14C]creatinine. Furthermore, apical
      excretion of [14C]creatinine was not dependent on acidification of the apical
      medium. CONCLUSIONS: Creatinine was subjected to directional transport across
      renal epithelial cells from the basolateral to apical side. The organic cation
      transporter should be involved in the basolateral uptake of creatinine.

PMID- 15988124
TI  - Identification of human UDP-glucuronosyltransferase isoform(s) responsible for
      the glucuronidation of 2-(4-chlorophenyl)- 5-(2-furyl)-4-oxazoleacetic acid (TA
      1801A).
AB  - We characterized the hepatic and intestinal UDP-glucuronosyltransferase (UGT)
      isoform(s) responsible for the glucuronidation of 2-(4-chlorophenyl)-5-(2-furyl)
      4-oxazoleacetic acid (TA-1801A) in humans through several in vitro mechanistic
      studies. Assessment of a panel of recombinant UGT isoforms revealed the TA-1801A
      glucuronosyltransferase activity of UGT1A1, UGT1A3, UGT1A7, UGT1A9, and UGT2B7.
      Kinetic analyses of the TA-1801A glucuronidation by recombinant UGT1A1, UGT1A3,
      UGT1A9, and UGT2B7 showed that the K(m) value for UGT2B7 was apparently
      consistent with those in human liver and jejunum microsomes. The TA-1801A
      glucuronosyltransferase activity in human liver microsomes was inhibited by
      bilirubin (typical substrate for UGT1A1), propofol (typical substrate for
      UGT1A9), diclofenac (substrate for UGT1A9 and UGT2B7), and genistein (substrate
      for UGT1A1, UGT1A3, and UGT1A9). The inhibition by bilirubin, propofol, and
      diclofenac of the TA-1801A glucuronidation was less pronounced in jejunum
      microsomes than liver microsomes, suggesting that the contribution of UGT1A1,
      UGT1A9, and UGT2B7 to the TA-1801A glucuronidation is smaller in the intestine
      than the liver. In contrast, genistein strongly inhibited the TA-1801A
      glucuronosyltransferase activity in both human liver and jejunum microsomes.
      These results suggest that the glucuronidation of TA-1801A is mainly catalyzed by
      UGT1A1, UGT1A9, and UGT2B7 in the liver, and by UGT1A1, UGT1A3, and UGT2B7 in the
      intestine in humans.

PMID- 15988123
TI  - Glucuronidation of 2-(4-chlorophenyl)-5-(2-furyl)-4-oxazoleacetic acid (TA-1801A)
      in humans: species differences in liver and intestinal microsomes.
AB  - The metabolism of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-4-oxazoleacetate (TA
      1801), a potent hypolipidemic agent, was studied in humans after oral
      administration and compared with that found in rats, rabbits, and dogs
      previously. Hydrolysis of the ethyl ester to produce metabolite M1 (TA-1801
      active form; TA-1801A) is the first metabolic step and the subsequent
      biotransformation includes the glucuronidation to form the metabolite M4 and the
      oxidation to form the metabolites M2 and M3. The metabolism of TA-1801 in humans
      was qualitatively similar to that in the experimental animals studied, although
      species differences were seen in the amount of metabolites. M4, the glucuronide
      of TA-1801A was the most abundant metabolite in human urine (24.3% of the dose).
      In vitro studies using human liver and jejunum microsomes indicated that the TA
      1801A glucuronosyltransferase activity in human jejunum microsomes was 2-fold
      higher than that in liver microsomes. With regard to the interspecies differences
      in the TA-1801A glucuronosyltransferase activities, the intrinsic clearance for
      the TA-1801A glucuronidation in liver microsomes was in the following order:
      rabbit>monkey>human=rat=dog. In jejunum microsomes, the intrinsic clearance for
      the TA-1801A glucuronidation was in the following order:
      human>monkey>rabbit>rat=dog. These results suggest that the species differences
      in the intestinal TA-1801A glucuronidation contribute to the species differences
      in the excretion rate of TA-1801A glucuronide into the urine.

PMID- 15988125
TI  - Simultaneous determination of single nucleotide polymorphisms of MDR1 genes by
      electrochemical DNA chip.
AB  - The on-chip genotyping system ("the electrochemical DNA chip") has been developed
      as a more cost-effective genotyping system and was applied to MDR1 genotyping in
      the present study, which is required for wide use in clinical application and for
      personalized medication based on genotype. The electrochemical DNA chip was
      optimized and applied to simultaneous genotyping of four MDR1 polymorphisms (T
      129C, C1236T, G2677(A,T) and C3435T) using synthetic model oligonucleotide DNA
      and human genomic DNA. The electrochemical DNA chip successfully gave the T-129C,
      C1236T, G2677(A,T) and C3435T genotypes, which were completely consistent with
      those determined by direct sequencing. In conclusion, the electrochemical DNA
      chip is useful for simultaneous determination of some genotypes and haplotypes,
      and efficient genotyping using this system can support future genotype-phenotype
      studies at a large scale.

PMID- 15988126
TI  - Inhibitory mechanism of papaverine on carbachol-induced contraction in bovine
      trachea.
AB  - We have demonstrated that the relaxing mechanism of papaverine in phasic muscles
      such as ileum, urinary bladder, and uterus is different from tonic muscles such
      as aorta. In this study, we examined the inhibitory mechanism of papaverine on
      carbachol (CCh)-induced contraction in the bovine trachea. Papaverine inhibited
      muscle contraction and increase in [Ca(2+)](i) level induced by CCh. Papaverine
      increased cAMP content but not cGMP content. Papaverine did not affect CCh
      induced oxidized flavoproteins fluorescence or reduced pyridine nucleotides
      fluorescence. Papaverine (30 microM) remarkably inhibited muscle tension, but
      slightly decreased creatine phosphate and ATP contents. Iberiotoxin restored the
      inhibitions of muscle contraction and [Ca(2+)](i) level induced by papaverine or
      dibutyryl-cAMP. These results suggested that the relaxing mechanism of papaverine
      in the bovine trachea is mainly due to increases of cAMP content by inhibiting
      phosphodiesterase and the mechanism is partially involved in the activation of BK
      channel by cAMP.

PMID- 15988127
TI  - Upregulation of phospholipase d expression and activation in ventricular pressure
      overload hypertrophy.
AB  - Evidence for a role of phospholipase D (PLD) in cellular proliferation and
      differentiation is accumulating. We studied PLD activity and expression in normal
      and hypertrophic rat and human hearts. In rat heart, abdominal aortic banding
      (constriction to 50% of original lumen) caused hypertrophy in the left ventricle
      (as shown by weight index and ANP expression) by about 15% after 30 days without
      histological evidence of fibrosis or signs of decompensation and in the right
      ventricle after 100 days. The hypertrophy was accompanied by small increases of
      basal PLD activity and strong potentiation of stimulated PLD activity caused by
      4beta-phorbol-12beta,13alpha-dibutyrate (PDB) and by phenylephrine. The mRNA
      expressions of both PLD1 and PLD2 determined by semiquantitative competitive RT
      PCR were markedly enhanced after aortic banding. In the caveolar fraction of the
      rat heart, PLD2 protein determined by Western blot analysis was upregulated in
      parallel with the expression of caveolin-3. A similar induction of PLD mRNA and
      protein expression was observed in hypertrophied human hearts of individuals (39
      45-year-old) who had died from non-cardiac causes. In conclusion, PLD1 and PLD2
      expressions were strongly enhanced both in rat and human heart hypertrophy, which
      may be responsible for the coincident potentiation of the PLD activation by alpha
      adrenoceptor and protein kinase C stimulation. These results are compatible with
      a significant role of PLD activation in cell signaling of ventricular pressure
      overload hypertrophy.

PMID- 15988128
TI  - Spatial learning of mice lacking a neuron-specific epidermal growth factor family
      protein, NELL2.
AB  - NELL2 is a neuron-specific thrombospondin-1-like extracellular protein containing
      six epidermal growth factor-like domains. We previously disrupted the NELL2 gene
      in mice by gene targeting and showed that long-term potentiation is enhanced in
      vivo in the dentate gyrus of NELL2-deficient mice. To further elucidate the
      physiological roles of NELL2, we performed a behavioral characterization of
      NELL2(-/-) and their heterozygous control mice. NELL2-deficient mice exhibited
      learning impairment in the Morris water maze task. However, we observed no
      difference in passive avoidance learning between NELL2(-/-) and NELL2(+/-) mice.
      These observations suggest that NELL2 plays an important role in hippocampus
      dependent spatial learning and that emotional learning does not depend critically
      on NELL2.

PMID- 15988129
TI  - Long-term effects of high doses of nicotine on feeding behavior and brain nitric
      oxide synthase activity in female mice.
AB  - We studied the long-term effects of repeated doses of nicotine, causing
      dependence, 120 days after its withdrawal on feeding behavior and on brain nitric
      oxide (NO) formation in female mice. Nicotine dependence was induced by
      subcutaneous (s.c.) nicotine injection (2 mg/kg, four injections daily) for 14
      days. Daily food intake was evaluated for the entire observational period (120
      days). Moreover, 30, 60, and 120 days after nicotine withdrawal, we evaluated
      food intake, nitrite/nitrate levels, and nitric oxide synthase (NOS) activity and
      expression in the hypothalamus after food deprivation (24 h). In animals in which
      nicotine dependence was induced (NM), daily food intake was similar to that of
      controls (M). However, following food deprivation, NM mice showed i) a
      significant increase in food intake, ii) changes in weight gain and in
      hypothalamic nitrite/nitrate levels, and iii) enhancement of hypothalamic
      neuronal NOS (nNOS) activity. Results indicate that high doses of nicotine
      producing dependence induce long-term changes in feeding behavior consequent to
      food deprivation associated to alterations in the brain nitrergic system.

PMID- 15988131
TI  - Changes in grain size and grain storage protein of rice (Oryza Sativa L.) in
      response to elevated UV-B radiation under outdoor conditions.
AB  - Variation in growth, grain size and grain storage protein content of rice (Oryza
      sativa L.) in response to elevated UV-B radiation under sunlight was examined in
      a cool rice-growing region of Miyagi Prefecture, Japan, in 1999, 2001 and 2002.
      Tiller number, dry mass, panicle number, grain yield and grain size significantly
      decreased under elevated UV-B radiation in 2001 and 2002. The effects of elevated
      UV-B radiation on the reduction of each growth parameter were greatly enhanced by
      daily lower temperature during the ripening stage in those two years. On the
      contrary, total grain nitrogen content and grain storage protein content
      significantly increased under elevated UV-B radiation in 2001 and 2002. Among
      grain storage proteins, glutelin content significantly increased but albumin
      globulin and prolamin contents did not. It was thus evident that not only grain
      size but also grain storage protein of rice was markedly influenced due to
      elevated UV-B radiation.

PMID- 15988132
TI  - Repeated irradiations with gamma-rays at a Dose of 0.5 Gy may exacerbate asthma.
AB  - We previously showed that 0.5 Gy whole-body gamma-ray irradiation with a single
      or small number of repeated exposures inhibits tumor growth in mice, via
      elevation of the IFN-gamma/IL-4 ratio concomitantly with a decrease in the
      percentage of B cells. Here we examined whether repeated 0.5 Gy gamma-rays
      irradiation can improve asthma in an OVA-induced asthmatic mouse model. We found
      that repeated irradiation (10 times) with 0.5 Gy of gamma-rays significantly
      increased total IgE in comparison with the disease-control group. The levels of
      IL-4 and IL-5 were also significantly higher in the gamma-ray-irradiated group,
      while that of IFN-gamma was significantly lower, resulting in a further decrease
      of the IFN-gamma/IL-4 ratio from the normal value. These results indicate that
      the repeated irradiation with gamma-rays may exacerbate asthma, and may have
      opposite effects on different immune reactions unlike the irradiation with a
      single or small number of repeated exposures.

PMID- 15988130
TI  - Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and
      neck cancer patients undergoing radiotherapy.
AB  - This study evaluated cytogenetic damage by measuring the frequency of
      micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck
      cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31
      patients before, during, and after radiotherapy, and in 17 healthy controls
      matched for gender, age, and smoking habits. Results showed no statistically
      significant difference between patients and controls prior to radiotherapy in
      cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment,
      increased MNC frequencies were observed in both cell types. Micronucleated
      lymphocyte levels remained high in samples collected 30 to 140 days after the end
      of treatment, while MNC frequency in buccal mucosa decreased to values
      statistically similar to baseline values. There is controversy over the effects
      of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However,
      increased frequency of micronucleated buccal mucosa cells was seen in patients
      under 60 years old and in those with tumors >4 cm. In conclusion, the data show
      that radiotherapy has a potent clastogenic effect in circulating lymphocytes and
      buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC
      frequency in these two tissues is not a sensitive marker for head-and neck
      neoplasm.

PMID- 15988133
TI  - CPD photolyase gene from Spinacia oleracea: repair of UV-damaged DNA and
      expression in plant organs.
AB  - The UV-B radiation contained in solar radiation has deleterious effects on plant
      growth, development and physiology. Specific damage to DNA caused by UV radiation
      involves the cyclobutyl pyrimidine dimers (CPD) and the pyrimidine (6-4)
      pyrimidone photoproducts. CPDs are repaired by CPD photolyase via a UV-A/blue
      light-dependent mechanism. The gene for the class II CPD photolyase has been
      cloned from higher plants such as Arabidopsis, cucumbers and rice. We isolated
      and characterized the cDNA and a genomic clone encoding the spinach class II CPD
      photolyase. The gene consisted of 3777 bases and 9 exons. The sequence of amino
      acids predicted from the nucleotide sequence of the cDNA of the gene was highly
      homologous to that of the higher plants listed above. When a photolyase-deficient
      Escherichia coli strain was transformed with the cDNA, photoreactivation activity
      was partially restored, by the illumination with photoreactivating light,
      resulting in an increased survival and decreased content of CPDs in the
      Escherichia coli genome. In both the male and female plants, the gene was highly
      expressed in leaves and flowers under the condition of 14-h light and 10-h dark
      cycle. The expression in the roots was quite low compared with the other organs.

PMID- 15988134
TI  - Radioprotective property of the ethanolic extract of Piper betel Leaf.
AB  - The radioprotective activity of Piper betel ethanolic extract (PE) has been
      studied using rat liver mitochondria and pBR 322 plasmid DNA as two model in
      vitro systems. The extract effectively prevented gamma-ray induced lipid
      peroxidation as assessed by measuring thiobarbituric acid reactive substrates,
      lipid hydroperoxide and conjugated diene. Likewise, it prevented radiation
      induced DNA strand breaks in a concentration dependent manner. The
      radioprotective activity of PE could be attributed to its hydroxyl and superoxide
      radicals scavenging property along with its lymphoproliferative activity. The
      radical scavenging capacity of PE was primarily due to its constituent phenolics,
      which were isolated and identified as chevibetol and allyl pyrocatechol.

PMID- 15988135
TI  - Identification of Skin injury-related genes induced by ionizing radiation in
      human keratinocytes using cDNA microarray.
AB  - The skin is an external organ that is most frequently exposed to radiation. High
      dose radiation initiates and promotes skin cancer and acute radiation injury. It
      is important to investigate the influence of high-dose radiation exposure on the
      skin at the molecular level to understand acute radiation injury. To identify
      genes that are associated with injury caused by high-dose radiation exposure of
      the skin, we used microarray technology to examine the effect of irradiation on
      approximately 1000 genes in normal human epidermal keratinocytes at 3 h
      postirradiation with a cytotoxic dose of X-ray (5 Gy). We found that 16 and 59
      genes were up- and down-regulated respectively in the keratinocytes. Several
      apoptosis-related genes, for example, BAK and TSC-22, and anti-proliferative
      genes, for example, BTG-1 and BTG-3, were up-regulated. We focused on ATF3
      because ATF3 is induced most strongly by X-irradiation, and its function in
      keratinocytes is unknown. The induction of the ATF3 mRNA and protein in
      keratinocytes following X-ray was confirmed by RT-PCR and western blot analysis.
      ATF3 was also induced and accumulated within the nuclei of keratinocytes after X
      ray irradiation in vivo and in vitro. Exogenous EYFP-ATF3 also accumulated within
      the nuclei of keratinocytes. In the transient expression assay, EYFP-ATF3, but
      not EYFP, induced apoptosis in keratinocytes. Taken together, these results
      suggest that ATF3 plays a role in apoptosis in keratinocytes and is associated
      with skin injury caused by ionizing radiation.

PMID- 15988136
TI  - Tumor induction in mice locally irradiated with carbon ions: a retrospective
      analysis.
AB  - Tumor induction in mice legs that were locally irradiated with carbon ions was
      compared to tumor induction by gamma rays after single and fractionated
      irradiation. A total of 250 tumors were induced in 1104 mice that received carbon
      ion doses of 5 through 65 Gy. A total of 77 tumors were induced in 371 mice that
      received gamma-ray doses of 45 through 95 Gy. Of 91 carbon-ion induced tumors
      examined histologically, 97 percent were malignant, and sarcomas such as
      malignant fibrous histiocytoma (47%) and fibrosarcoma (32%) were most frequently
      observed. Malignant fibrous histiocytoma was also the most frequently observed
      tumor (12 out of 20 tumors; 60%) after gamma-ray irradiation, followed by
      carcinomas (25%) such as adenocarcinoma and squamous cell carcinoma. Neither dose
      fractionation nor linear energy transfer affected tumor induction for carbon ions
      and gamma rays. Dose responses were linear for carbon ions and gamma rays, and
      showed no saturation up to 65 Gy of carbon ions and 95 Gy of gamma rays. The
      relative biological effectiveness of carbon ions was 2.2 for tumor induction and
      1.9 for early skin reaction. We conclude that risk of secondary tumor induction
      by carbon-ion radiotherapy would not be seriously higher than anticipated.

PMID- 15988138
TI  - Differences in effects of oncogenes on sensitivity to anticancer drugs.
AB  - Methods to predict the responsiveness of a particular tumor to a particular
      anticancer drug are desirable not only for chemotherapy but also for
      chemoradiotherapy. Here, we examined the effects of viral or activated oncogenes
      on sensitivity to anticancer drugs by using SHOK (Syrian hamster Osaka-Kanazawa)
      cells and their transfectants. The IC50 of each transfectant was compared with
      that of the pSV2Neo transfected control. Cells transfected with the c-myc, v-mos,
      or v-fgr gene increased their sensitivity to bleomycin, while those transfected
      with the H-ras gene developed resistance. Resistance to cisplatin was conferred
      by the introduction of the H-ras or c-cot gene. In the case of adriamycin, the c
      myc or c-cot transfectant increased sensitivity and the H-ras transfectant
      decreased it. Mitomycin C resistance was observed by the introduction of the K
      ras gene. Thus, the H-ras gene was found to be involved in the development of
      resistance to three of the four anticancer drugs. In addition, we have for the
      first time shown that mos and cot have an effect on sensitivity to three and all
      of the four anticancer drugs, respectively. These results suggest that the
      expression of each oncogene would differently affect sensitivity to the four
      anticancer drugs used in this study, and this property could be a possible marker
      to predict chemosensitivity.

PMID- 15988137
TI  - Induction of micronuclei in CHO cells by bleomycin but not by X-irradiation is
      decreased by treatment with HMG-CoA reductase inhibitors.
AB  - We investigated the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors, pravastatin and fluvastatin, on the induction of
      micronuclei by ionizing radiation or bleomycin in Chinese hamster ovary cells in
      order to assess the radical-scavenging ability of these inhibitors. The results
      indicated that both pravastatin and fluvastatin had no effect on the induction of
      micronuclei by X-irradiation when they were applied for either pre-treatment or
      post-treatment. In contrast, both drugs effectively reduced the frequency of
      bleomycin-induced micronuclei when they were applied for simultaneous treatment
      or post-treatment, but not for pre-treatment. This indicates that the radical
      scavenging ability of these two HMG-CoA reductase inhibitors differs according to
      the origins of the radicals--e.g., X-rays or bleomycin--even when the two drugs
      are compared at an equivalent cytotoxic dose. Our results suggest that both
      pravastatin and fluvastatin have the ability to scavenge certain types of
      radicals and to protect cells against oxidative stress.

PMID- 15988139
TI  - The Shizosaccharomyces pombe homolog (SpMYH) of the Escherichia coli MutY is
      required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent G:C
      to C:G transversions.
AB  - The frequency of G:C-->C:G transversions significantly increases upon exposure of
      cells to ionizing radiation or reactive oxygen species. Transversions can be
      prevented by base excision repair, which removes the causative modified bases
      from DNA. Our previous studies revealed that MutY is responsible for removing
      guanine from 7,8-dihydro-8-oxoguanine/guanine mispairs (8-oxoG/G) and prevents
      the generation of G:C-->C:G transversions in E. coli. SpMYH, a homolog of E. coli
      MutY, had been identified and characterized in the fission yeast S. pombe.
      Purified SpMYH has adenine DNA glycosylase activity on A/8-oxoG and A/G mismatch
      containing oligonucleotides. In this study, we examined whether SpMYH has a
      similar activity allowing it to remove G from 8-oxoG/G in DNA. The purified SpMYH
      tightly bound to duplex oligonucleotides containing 8-oxoG/G and removed the
      unmodified G from 8-oxoG/G as efficiently as A from 8-oxoG/A. The activity was
      absent in the cell extract prepared from an SpMYH-knockout strain of S. pombe.
      The expression of SpMYH markedly reduced the frequency of spontaneous G:C-->C:G
      transversions in the E. coli mutY mutant. These results demonstrate that SpMYH is
      involved in the repair of 8-oxoG/G, by which it prevents mutations induced by
      oxidative stress in S. pombe.

PMID- 15988141
TI  - Non-homologous end-joining genes are not inactivated in human radiation-induced
      sarcomas with genomic instability.
AB  - DNA double-strand break (DSB) repair pathways are implicated in the maintenance
      of genomic stability. However the alterations of these pathways, as may occur in
      human tumor cells with strong genomic instability, remain poorly characterized.
      We analyzed the loss of heterozygosity (LOH) and the presence of mutations for a
      series of genes implicated in DSB repair by non-homologous end-joining in five
      radiation-induced sarcomas devoid of both active Tp53 and Rb1. LOH was
      recurrently observed for 8 of the 9 studied genes (KU70, KU80, XRCC4, LIG4,
      Artemis, MRE11, RAD50, NBS1) but not for DNA-PKcs. No mutation was found in the
      remaining allele of the genes with LOH and the mRNA expression did not correlate
      with the allelic status. Our findings suggest that non-homologous end-joining
      repair pathway alteration is unlikely to be involved in the high genomic
      instability observed in these tumors.

PMID- 15988140
TI  - Preferential sensitization of tumor cells to radiation by heat shock protein 90
      inhibitor geldanamycin.
AB  - The purpose of this study was to investigate the radiosensitizing effect of
      geldanamycin (GA), an inhibitor of heat shock protein 90, on tumour cells and
      normal cells. We tested the effect of a combination of GA and radiation on cell
      survival, PI3K/Akt-related proteins and apoptosis induction. GA sensitized tumour
      cells to radiation in preference to normal cells. In addition, a combination of
      radiation and GA abolished Akt activities and strongly enhanced the induction of
      apoptosis in tumour cells which depend on Akt protein activities for cell
      survival. The present data support the hypothesis that GA sensitizes tumour cells
      by modulating the balance among mitogenic, antiproliferative and apoptotic
      pathways. Targeting Hsp90 in tumour cells may lead to the development of new
      radiosensitizing strategies in radiotherapy.

PMID- 15988142
TI  - Evaluation of radioprotective effects of Rajgira (Amaranthus paniculatus) extract
      in Swiss albino mice.
AB  - The radioprotective efficacy of aqueous extract of Rajgira (Amaranthus
      paniculatus) leaves against whole body gamma radiation was studied in Swiss
      albino mice. The oral administration of Rajgira extract at 800 mg/kg body
      weight/day for 15 consecutive days before whole body exposure to radiation was
      found to be effective with the LD50/30 values of 6.33 and 8.62 Gy for irradiation
      alone and Rajgira+irradiation group, respectively, giving a dose reduction factor
      of 1.36. This effect of Rajgira accompanied the increased endogenous spleen
      colonies and the spleen weight without any side effect or toxicity, as well as
      the modulation of the radiation-induced decrease of reduced glutathione and the
      radiation-induced increase in lipid peroxidation assessed in the liver and the
      blood.

PMID- 15988143
TI  - Pretreatment with rituximab enhances radiosensitivity of non-Hodgkin's lymphoma
      cells.
AB  - The present study examines the effects of ionizing radiation in combination with
      rituximab (RTX), a chimeric human anti-CD20 monoclonal antibody, on
      proliferation, cell cycle distribution and apoptosis in B-lymphoma RL and Raji
      cells. Exposure to ionizing radiation (9 Gy) induced cell growth delay and
      apoptosis in RL cells, whereas Raji cells showed moderate radio-resistance. The
      simultaneous exposure of lymphoma cells to ionizing radiation and RTX (10
      microg/mL) markedly enhanced apoptosis and cell growth delay in RL and Raji
      cells. Cooperative antiproliferative and apoptotic effects of RTX and radiation
      were achieved through the inhibition of c-myc and bcl-XL expression. Furthermore,
      RTX-modulated expression of cell cycle regulating proteins, such as p53,
      p21/WAF1, p27/KIP1, contributed to the development of radiation-induced cell
      killing and growth arrest. Each NHL cell line that underwent apoptosis induced by
      combination treatment revealed enhanced caspase-3 and poly (ADP-ribose)
      polymerase (PARP) cleavage as compared to only irradiated cells. These findings
      show that rituximab synergistically enhances radiation-induced apoptosis and cell
      growth delay through the expression of proteins involved in the programmed cell
      death and cell cycle regulation pathways.

PMID- 15988144
TI  - Aml1 gene rearrangements and mutations in radiation-associated acute myeloid
      leukemia and myelodysplastic syndromes.
AB  - Several studies suggested a causal link between AML1 gene rearrangements and both
      radiation-induced acute myeloid leukaemia (AML) and myelodysplastic syndromes
      (MDS). Fifty-three AML samples were analyzed for the presence of AML1
      abnormalities using fluorescent in-situ hybridization (FISH) and reverse
      transcription polymerase chain reaction (RT-PCR). Of these patients, 24 had
      experienced radiation exposure due to the Chernobyl accident, and 29 were non
      irradiated spontaneous AML cases and served as controls. AML1/ETO translocations
      were found in 9 of 29 spontaneous AML but only in 1 of 24 radiation-associated
      AML cases. This difference between translocation frequencies is statistically
      significant in the age-unstratified cohorts (p=0.015). Following age
      stratification, the difference becomes less pronounced but remains on borderline
      significance (p=0.053). AML1 mutation status was assessed in 5 clean-up workers
      at Chernobyl NPP with MDS, or AML following MDS, by direct sequencing of genomic
      DNA from the coding region (exon 3 through 8). In one patient who developed MDS
      following an acute radiation syndrome, a hexanucleotide duplication of CGGCAT in
      exon 8 was found, inserted after base position 1502. Our results suggest that
      AML1 gene translocations are infrequent in radiation-induced leukemogenesis but
      are consistent with the idea that radiation may contribute to the development of
      MDS through AML1 gene mutation.

PMID- 15988145
TI  - Combined exposure of ELF magnetic fields and x-rays increased mutant yields
      compared with x-rays alone in pTN89 plasmids.
AB  - We have examined mutations in the supF gene carried by pTN89 plasmids in
      Escherichia coli (E. coli) to examine the effects of extremely low frequency
      magnetic fields (ELFMFs) and/or X-rays to the plasmids. The plasmids were
      subjected to sham exposure or exposed to an ELFMF (5 mT), with or without X-ray
      irradiation (10 Gy). For the combined treatments, exposure to the ELFMF was
      immediately before or after X-ray irradiation. The mutant fractions were 0.94x10(
      5 )for X-rays alone, 1.58x10(-5) for an ELFMF followed by X-rays, and 3.64x10(-5)
      for X-rays followed by an ELFMF. Increased mutant fraction was not detected
      following exposure to a magnetic field alone, or after sham exposure. The mutant
      fraction for X-rays followed by an ELFMF was significantly higher than those of
      other treatments. Sequence analysis of the supF mutant plasmids revealed that
      base substitutions were dominant on exposure to X-rays alone and X-rays plus an
      ELFMF. Several types of deletions were detected in only the combined treatments,
      but not with X-rays alone. We could not find any mutant colonies in sham
      irradiated and an ELFMF alone treatment, but exposure to ELFMFs immediately
      before or after X-ray irradiation may enhance the mutations. Our results indicate
      that an ELFMF increases mutation and alters the spectrum of mutations.

PMID- 15988146
TI  - Transcriptional response of human umbilical vein endothelial cells to low doses
      of ionizing radiation.
AB  - We used cDNA microarray hybridization technology to monitor the transcriptional
      response of Human Umbilical Vein Endothelial (HUVEC) cells to x-rays doses
      ranging from 2 to 200 cGy. An early time window from irradiation (4h) was
      selected in order to minimize the effects of the cell cycle blockage eventually
      induced at high doses of irradiation. Three different gene-clustering algorithms
      have been used to group the 4134 monitored ORF based on their transcriptional
      response in function of the irradiation dose. The results show that while few
      genes exhibit a typical dose-dependent modulation with a variable threshold, most
      of them have a different modulation pattern, peaking at the two intermediate
      doses. Strikingly even the lowest dose used (2 cGy) seems to be very effective in
      transcriptional modulation. These results confirm the physiological relevance of
      sublethal-dose exposures of endothelial cells and strengthens the hypothesis that
      alternative dose-specific pathways of radioadaptive response exist in the
      mammalian cells. 111 genes were found to be modulated at all doses of
      irradiation. These genes were functionally classified by cellular process or by
      molecular function. Genes involved in coagulation and peroxidase activity and
      structural constituent of ribosomes were over-represented among the up-regulated
      genes as compared with their expected statistical occurrence. Three genes coding
      for regulatory kinase activities (CDK6; PRCKB1 and TIE) are found down-regulated
      at all doses of irradiation.

PMID- 15988147
TI  - Radioprotective effects of melatonin on radiation-induced cataract.
AB  - One of the mechanisms proposed to explain lens opacification is the oxidation of
      crystallins, either by radiation or reactive oxygen species (ROS). It has been
      shown that melatonin has both an anti-peroxidative effect on several tissues and
      a scavenger effect on ROS. The purpose of this study was to determine the
      antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in
      the lens after total-cranium irradiation of rats with a single dose of 5 Gy.
      Sprague-Dawley rats were divided into four groups. Control group received neither
      melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats
      (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single
      dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups
      were administered 5 mg/kg melatonin daily by intraperitoneal injections during
      ten days. Chylack's cataract classification was used in this study. At the end of
      the 10th day, the rats were killed and their eyes were enucleated to measure the
      antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde
      (MDA)). Irradiation significantly increased the MDA level, as an end product of
      lipid peroxidation, and also significantly decreased SOD and GSH-Px activity,
      emphasizing the generation of increased oxidative stress. Rats injected with
      melatonin only did not cause cataract formation. Melatonin supplementation with
      irradiation significantly increased the activity of SOD and GSH-Px enzymes and
      significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a
      single dose enhanced cataract formation, and melatonin supplementation protected
      the lenses from radiation-induced cataract formation. Our results suggest that
      supplementing cancer patients with adjuvant therapy of melatonin may reduce
      patients suffering from toxic therapeutic regimens such as chemotherapy and/or
      radiotherapy and may provide an alleviation of the symptoms due to radiation
      induced organ injuries.

PMID- 15988149
TI  - Early growth of experimental lung metastasis in mouse.
AB  - A radiobiological method was developed to measure the initial growth of
      clonogenic tumor cells metastasizing to the lung. The thoraxes of mice were
      externally irradiated by g rays after an intravenous transplantation of syngeneic
      fibrosarcoma cells. The lung colonies which developed 11 days after irradiation
      were counted and provided surviving fractions. Survival curves moved downward
      when the time interval between transplantation and radiation was delayed from 1
      to 21 hr, but shifted upward at 48 hr or later. Survival ratios at given doses
      and the extrapolation number of survival curves fitted to multi-target model were
      calculated, and plotted against time after the intravenous transplantation.
      Doubling times of 13.3 and 13.1 hr were obtained by use of the survival ratio and
      of the extrapolation number, respectively. This method is useful to measure the
      growth dynamics of clonogenic tumor cells at the site of a metastasized organ.

PMID- 15988148
TI  - A cytogenetic study of Korean native goat bred in the nuclear power plant using
      the micronucleus assay.
AB  - Cytogenetic and hematological analysis was performed on the peripheral blood
      lymphocytes (PBLs) obtained from Korean native goats bred in two nuclear power
      plants (Wolsong and Uljin) and a control area. The frequencies of gamma-ray
      induced micronuclei (MN) in the cytokinesis-blocked (CB) lymphocytes at several
      doses were measured in three Korean native goats. The measurements performed
      after irradiation showed dose-related increases in the MN frequency in each of
      the donors. The results were analyzed using a linear-quadratic model with a line
      of best fit of y=0.1019D+0.0045D2+0.0093 (y=number of MN/CB cells and
      D=irradiation dose in Gy). The MN rates in the goats from the Wolsong and Uljin
      nuclear power plant, and the control area were 9.60+/-2.88, 6.83+/-1.47 and
      9.88+/-4.32 per 1,000 CB lymphocytes, respectively. The apparent difference is
      not statistically significant. The MN frequencies of PBLs from goats bred in
      three areas means that the values are within the background variation in this
      experiment. The MN frequencies and hematological values were similar regardless
      of whether the goats were bred in the nuclear power plant or the control area.

PMID- 15988150
TI  - Ca2+ entry channels involved in endothelin-1-induced contractions of vascular
      smooth muscle cells.

PMID- 15988151
TI  - Dependency of endothelial cell function on vascular smooth muscle cells in guinea
      pig mesenteric arteries and arterioles.
AB  - Using guinea-pig mesenteric arteries and arterioles, we investigated the membrane
      potential of endothelial cells at rest and during application of acetylcholine
      (ACh) with and without the smooth muscle layers attached. When smooth muscle and
      endothelial layers were in close apposition, the resting membrane potentials of
      the two types of cells were closely related and were slightly more negative in
      the smooth muscle cells than in the endothelial cells. Once the endothelial layer
      was separated from the smooth muscle layer, the endothelial cells depolarized
      (the average, -4.2 mV). In the isolated endothelial layer, ACh did not induce a
      membrane hyperpolarization as expected, but did induce a quick depolarization
      soon after conventional whole-cell recording was started. However, as the pipette
      solution (high K+) gradually diffused into the endothelial layer, the membrane
      response to ACh gradually changed toward hyperpolarization. ACh-induced
      hyperpolarization was also observed after incubating preparations in a high
      potassium bath solution. Our results indicate that vascular smooth muscle cells
      and endothelial cells are influencing each other as a functional unit and that
      the endothelial cells rely on the smooth muscle cells for their intracellular
      ionic composition and resting membrane potential.

PMID- 15988152
TI  - Diminution of angiotensin II-induced contraction of the abdominal aorta isolated
      from Watanabe heritable hyperlipidemic rabbits.
AB  - The purpose of this study was to investigate the changes in vasocontractile
      responses in atherosclerosis, using abdominal aortic strips isolated from
      Watanabe heritable hyperlipidemic (WHHL) rabbits and Japanese White (control)
      rabbits. The aortic strips from WHHL rabbits showed a significantly lower
      contractile response to angiotensin II than that in strips from control rabbits.
      The contractile responses to phenylephrine and 5-hydroxytryptamine were not
      different in WHHL and control groups. The contractile response to angiotensin II
      was higher in endothelium-denuded aortic strips than in endothelium-intact
      strips, but to a greater extent in the control group than in the WHHL group. The
      contractile response to angiotensin II in the absence of the endothelium was also
      lower in the WHHL group than in the control group. Pretreatment with N(G)-nitro-L
      arginine significantly increased the contractile response to angiotensin II in
      the endothelium-intact aortic strips in both the WHHL and control groups, while
      pretreatment with diclofenac did not affects the aortic contractile response to
      angiotensin II. The contractile responses to angiotensin II in the presence of
      N(G)-nitro-L-arginine and diclofenac were lower in the WHHL group than in the
      control group. The contractile response to angiotensin II in the presence of
      PD123319 was also lower in the WHHL group than in the control group. Endothelium
      dependent relaxation by acetylcholine occurred to the some extent in the WHHL and
      control groups. These results suggest that the WHHL rabbit abdominal aorta
      displays attenuated angiotensin II-induced contraction, mainly due to an
      abnormality in the angiotensin II-specific contractile pathway of the medial
      smooth muscle.

PMID- 15988153
TI  - Motor and electrogastrographic activity of the gastric tube formed after
      esophagectomy.
AB  - In order to characterize the motor activity of a surgically constructed gastric
      tube, several hours of ambulatory intraluminal pressure recordings were performed
      in 6 patients following esophagectomy and gastric tube construction. Whole
      pressure waves were spectrally analyzed by Fast Fourier Transform (FFT).
      Simultaneous abdominal and thoracic electrogastrograms (EGGs) were recorded for
      about 20 min both before and after meals during ambulatory pressure recording.
      The pressure waves and EGGs for each 20 min recording were analyzed by the
      maximal entropy method (MEM). While the motility index of the pressure waves
      decreased after a meal, the 3 cpm component of these waves (2.4-3.7 cpm)
      increased significantly (n=6, P<0.05). Both bradygastria (0-2.4 cpm) and the
      duodeno-respiratory component (10-15 cpm) decreased, while the tachygastria
      component (3.7-10 cpm) increased, although these differences were not
      significant. The peak power of the gastric tube abdominal EGGs was significantly
      larger than that of control abdominal or thoracic EGGs in each of the 1 cpm (0
      2.4 cpm), 6 cpm (5.0-7.4) and 8 cpm components (7.5-9.9). The thoracic EGG
      consisted mainly of the 3 cpm component, while the spectral amplitudes of the 1,
      6, 8 and 10 cpm components were below 6% of the 3 cpm component. The peak
      spectral frequency both of the intraluminal pressure waves by FFT and of the
      thoracic EGGs by MEM occurred within the 3 cpm component. A cross correlation of
      about 0.2-0.3 occurred between the thoracic EGGs and the intraluminal pressure
      waves. Thus the gastric tube seems to preserve most of the original gastric motor
      characteristics and to contribute as a substitute for the original esophagus and
      stomach.

PMID- 15988154
TI  - Effect of phorbol 12,13-dibutyrate on smooth muscle tone in rat stomach fundus.
AB  - We investigated the effects of phorbol 12,13-dibutyrate (PDBu), a typical protein
      kinase C (PKC) activator, on smooth muscle tone in the rat stomach fundus. In 5
      hydroxytriptamine (5-HT)-precontracted stomach fundus strips, PDBu induced dose
      dependent relaxation, but 4alpha-phorbol 12,13-didecanoate, a phorbol ester that
      does not activate PKC, did not induce relaxation. A PDBu-induced dose-dependent
      relaxation was also observed in strips precontracted with platelet-activating
      factor (PAF), carbachol, or 60 mM K+. In stomach fundus strips pretreated with
      PDBu, the contractile responses to 5-HT and PAF were completely blocked, but
      those induced by carbachol and endothelin-1 (ET-1) were only partially inhibited.
      In stomach fundus strips preincubated with carbachol in Ca2+-free medium, the
      Ca2+-induced contraction was decreased by preincubation with PDBu. In strips
      preincubated with 5-HT, PAF, or ET-1 in Ca2+-free medium, Ca2+-induced
      contractions were greatly inhibited by pretreatment with PDBu. These results
      suggest that in rat stomach fundus strips, PDBu-induced relaxation is mediated by
      activation of PKC. We speculate that a major factor mediating the relaxant action
      of PDBu in rat stomach fundus smooth muscle is represented by a reduction in Ca2+
      influx via an inhibition of Ca2+ channels.

PMID- 15988155
TI  - A trajectory of increasing activity and the elaboration of chemosensory modality:
      a new perspective on vertebrate origins.
AB  - This article reviews recent advances in comparative biological studies of
      vertebrate origins, with the aim of revisiting the long-standing controversy
      concerning these origins. Since early vertebrate evolution is paralleled by an
      evolutionary trend towards increasing activity, I focus on the evolution of
      respiratory and circulatory systems and discuss their potential roles in early
      vertebrate evolution. I give particular attention to the nasohypophyseal duct, an
      orifice characteristically found in agnathan vertebrates, and hypothesize that
      this duct originally functioned to convey oxygen dissolved in seawater to the
      respiratory gills. The chemosensory cell population that originated from the wall
      of the duct became the incipient olfactory organ and played a role in the
      organization of feeding behavior. An increase in chemosensory receptor genes via
      large-scale genomic evolution in the vertebrate lineage caused the repertoire of
      chemosensory cells to diversify and led to the appearance of the integrative
      center, including telencephalic structures typically lacking in protochordates.

PMID- 15988156
TI  - Genetic diversity in domestic cats Felis catus of the Tsushima Islands, based on
      mitochondrial DNA cytochrome b and control region nucleotide sequences.
AB  - Nucleotide sequences of mitochondrial DNA (mtDNA) of 50 domestic cats (Felis
      catus) obtained from the Tsushima Islands were determined and the genetic
      diversity was analyzed. In the cats, six haplotypes of the complete cytochrome b
      sequences (1,140 base-pairs, bp) and ten haplotypes of the partial control region
      sequences (350 bp) were identified. Haplotypes obtained from both genes showed
      existence of at least 11 maternal lineages of domestic cats in Tsushima. Mean
      values of polymorphic site numbers and sequences differences in the control
      region were 2.4 times and 1.8 times higher than those in the cytochrome b gene,
      respectively. Our results support the idea that the evolutionary rate of the
      control region was faster than that of the cytochrome b as reported in other
      mammals. Molecular phylogenetic trees showed the similar clustering of haplotypes
      for both genes. Meanwhile, no individual variations within the Tsushima leopard
      cat (Felis bengalensis euptilura), which is native to Tsushima, were observed,
      possibly as a result of genetic drift in the small ancestral population by
      geographical isolation. In contrast, the diversity of the domestic cat population
      was higher than that of the leopard cats, because the genetic variability of the
      former's founders, which were repeatedly brought to Tsushima in the past, still
      remains. In addition, no sequences of the leopard cat mtDNA were detected in any
      domestic cats. However, because the possibility that the domestic cat would
      crossbreed with the leopard cat cannot be denied, genetic monitoring of two
      species is necessary to biological conservation in Tsushima.

PMID- 15988157
TI  - Tungstate-induced color-pattern modifications of butterfly wings are independent
      of stress response and ecdysteroid effect.
AB  - Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase)
      inhibitor, to pupae immediately after pupation have been shown to efficiently
      produce characteristic color-pattern modifications on the wings of many species
      of butterflies. Here we demonstrated that the tungstate-induced modification
      pattern was entirely different from other chemically-induced ones in a species of
      nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic
      injections of tungstate produced characteristic expansion of black area and
      shrinkage of white area together with the move of parafocal elements toward the
      wing base. Overall, pattern boundaries became obscure. In contrast, an entirely
      different modification pattern, overall darkening of wings, was observed by the
      injections of stress-inducing chemicals, thapsigargin, ionomycin, or
      geldanamycin, to pupae under the rearing conditions for the adult summer form. On
      the ventral wings, this darkening was due to an increase of the proportion of
      peppered dark scales, which was reminiscent of the natural fall form of this
      species. Under the same rearing conditions, the injections of ecdysteroid, which
      is a well-known hormone being responsible for the seasonal polyphenism of
      nymphalid butterflies, yielded overall expansion of orange area especially around
      eyespots. Taken together, we conclude that the tungstate-induced modifications
      are clearly distinguishable from those of stress response and ecdysteroid effect.
      This conclusion then suggests that the putative PTPase signaling pathway that is
      sensitive to tungstate uniquely contributes to the wing-wide color-pattern
      development in butterflies.

PMID- 15988158
TI  - Alternative male mating behaviors dependent on relative body size in captive oval
      squid Sepioteuthis lessoniana (Cephalopoda, Loliginidae).
AB  - We observed the reproductive behavior of the oval squid Sepioteuthis lessoniana
      in captivity. The male used three different mating behaviors: male-parallel (MP),
      male-upturned (MU) and sneaking. Male competition over females frequently
      occurred before and during the female egg-laying period, and the outcome of most
      fights depended on male body size. Larger males guarded their partners from other
      males and performed MP mating during the egg-laying period of the paired females.
      In contrast, there was no pairing and mate guarding in MU mating and sneaking,
      which were adopted by smaller subordinate males as alternative tactics outside
      female egg-laying period and during the period, respectively. MP matings were 95%
      successful, but more than half of MU matings were unsuccessful. Higher mating
      success in MP mating was achieved through pairing, whereas males in MU mating
      were less successful because mating attempts without pair formation were often
      foiled by escape of the female. Sneaking was successful in all cases but occurred
      less frequently. Spermatophores were attached at the opening of the oviduct in MP
      mating, whereas they were attached around the female buccal membrane in MU mating
      and sneaking. Considering the route of egg transportation, higher fertilization
      success can be expected in MP mating because of the advantageous location of the
      attached spermatophores. Our results suggest that MP mating is used by larger,
      paired males during the female egg-laying period, and that MU mating and sneaking
      are alternative tactics adopted by smaller, subordinate males. These alternative
      mating behaviors would be conditional strategy dependent on relative body size,
      because some individual males displayed both MP and MU mating behaviors.

PMID- 15988159
TI  - A skeletochronological study on a subtropical, riparian ranid (Rana swinhoana)
      from different elevations in Taiwan.
AB  - We estimated the age, longevity, and growth patterns of a subtropical ranid, Rana
      swinhoana from high (Lishing) and low (Wulai) elevations using skeletochronology.
      In addition, we also measured body mass and length of frogs from five other
      localities. Results showed that both snout-vent length and body mass of frogs
      were significantly correlated with altitudes for both sexes. Frogs of Lishing
      were significantly larger and older than that of Wulai. We used LAGs to estimate
      the age and growth of frogs and found that the growth of Wulai frog of both sexes
      slowed down at an earlier age than that of Lishing frogs. Male and female frogs
      from Wulai did not exceed 6 and 7 years, respectively, while the maximum age of
      males and females of Lishing was 7 and 11 years, respectively. Results suggest
      that the LAGs observed in R. swinhoana correspond to low temperature and/or
      decreased food availability instead of desiccation during the harsh annual period
      (November to February). Skeletochronological data suggest that the variations of
      body size of R. swinhoana among elevations are likely associated with the growth,
      age at sexual maturity, and longevity.

PMID- 15988160
TI  - Intraspecific contact and egg production in the massive coral Goniastrea aspera
      in Okinawa, subtropical Japan.
AB  - The effect of intraspecific contact (Contact) on egg production was examined in
      the massive coral Goniastrea aspera in Okinawa, subtropical Japan. The contact
      was non-aggressive without damaging soft tissues each other. Within Contact
      colonies, polyp volume, polyp fertility (%polyps with gonad), and NE/PV (number
      of eggs per polyp volume) were significantly smaller in marginal (Mg) polyps
      without direct intraspecific contact than other polyps, but no difference was
      found between non-marginal and Mg-Contact (marginal with direct intraspecific
      contact) polyps. Comparisons of non-marginal polyps (non-marginal and Mg-Contact
      polyps were combined in Contact colonies) between Non-Contact and Contact
      colonies showed that fertility and NE/PV were significantly larger in Contact
      colonies than in Non-Contact colonies, but polyp volume were not different
      significantly. Further analyses dividing colonies at Non-Contact maturation
      colony size (60 polyps) revealed that fertility and NE/PV were significantly
      larger in Contact colonies than in Non-Contact colonies only in the small
      colonies (<60 polyps), indicating that the intraspecific contact promoted sexual
      maturation at smaller colony size; one polyped Contact coral was also
      reproductive. The lack of correlation between polyp volume and NE/PV in the small
      Contact colonies, and the similarity of NE/PV in non-marginal and Mg-Contact
      polyps within a colony, suggest that the maturation at smaller size in Contact
      colonies is realized by reproductive integration of polyps at the colony level.
      The present results show that size-structured populations such as colonial corals
      may show phenotypic diversity in key demographic parameters, such as reproductive
      output, dependent on ecological conditions.

PMID- 15988161
TI  - Effects of photoperiod and food availability on growth, leptin, sexual maturation
      and maintenance in the Mongolian gerbils (Meriones unguiculatus).
AB  - Reproductive activity of Mongolian gerbils is regulated by photoperiod
      nevertheless body weight regulation is controlled without ambient photoperiod.
      Food intake is a major factor affecting rodent reproductive efficiency. Leptin is
      a hormone secreted by adipose tissue and modulates food intake, energy
      expenditure and body fat stores. In this study we studied the interaction of
      photoperiod and food availability on growth, sexual maturation and leptin
      concentration in the male and female gerbils. Gerbils were gestated and reared in
      either 14L:10D or 2L:22D. At weaning, gerbils were housed individually and
      divided into three groups: fed ad libitum, fed 80% of ad libitum or fed 60% of ad
      libitum. Body weights were recorded at weaning and every week thereafter. After
      twelve weeks of treatment, animals were sacrificed and testes and uterine weights
      were determined and blood was collected for leptin measurement. Food restriction
      reduced body weight and inhibited reproductive development. Absolute paired
      testis weights were similar in ad lib and 80% of ad lib groups but significantly
      different compared with the 60% of ad lib group in both photoperiods. Body
      weights were also directly dependent upon the level of food restriction. Uterine
      mass was only affected in the 60% of ad lib group in 14L but both food
      restriction levels significantly affected the uterine weights in 2L. Significant
      variations were found in leptin profiles. Leptin concentration was highest in ad
      lib and 80% of ad lib groups and lowest in 60% of ad lib groups. These results
      suggest that the reproductive activity of Mongolian gerbils is sensitive to food
      intake and multiple potential environmental cues (e.g., food availability,
      temperature) can be utilized.

PMID- 15988162
TI  - New complete mitochondrial DNA sequence of the lancelet Branchiostoma lanceolatum
      (Cephalochordata) and the identity of this species' sequences.
AB  - Three mitochondrial (mt) genes were sequenced for two Atlantic lancelet species,
      Branchiostoma lanceolatum and B. floridae, to examine a serious discrepancy among
      previously published results of molecular studies: substantial sequence
      difference in a nuclear gene vs. virtual identity in the mt genome sequence. The
      results revealed that three mt genes of B. lanceolatum, collected from Helgoland
      in the North Sea and Naples in the Mediterranean, were quite diverged from those
      of B. floridae, collected from Tampa Bay, Florida. Therefore, the previously
      recognized identity in the mt genome between the two species is attributable to
      misidentification of materials used. To correct this misleading information, the
      complete mtDNA sequence of B. lanceolatum was determined for an individual from
      Helgoland.

PMID- 15988163
TI  - Localization and developmental expression of mRNA for cortical rod protein in
      kuruma prawn Marsupenaeus japonicus.
AB  - The mature penaeid oocytes possess cortical rods that contain two related
      cortical rod proteins (CRP, 28.6 kDa and 30.5 kDa). In the present study,
      localization of CRP mRNA and gene expression profiles of CRP and vitellogenin
      (Vg) during ovarian development were examined in kuruma prawn, Marsupenaeus
      japonicus, an economically important species for shrimp and prawn farming.
      Northern blot analysis revealed that CRP mRNA was expressed in the ovary. In situ
      hybridization showed strong signals for CRP transcripts in the oocytes at early
      developmental stages in both immature and mature ovaries. Quantitative analysis
      by real-time polymerase chain reaction revealed that CRP mRNA levels were higher
      in the previtellogenic and endogenous (primary) vitellogenic stages than in more
      advanced stages. Unlike CRP mRNA, Vg mRNA levels were low in the ovary and
      hepatopancreas in previtellogenic females. When the ovary developed into the
      endogenous vitellogenic stage, ovarian Vg mRNA levels increased significantly,
      followed by rapid decrease in more advanced stages. The Vg mRNA levels in the
      hepatopancreas, on the other hand, tended to be high in the exogenous (secondary)
      vitellogenic and maturation stages, in which ovarian Vg mRNA levels were
      decreased. Our findings indicate that CRP mRNA is highly expressed before the
      onset of vitellogenesis, suggesting that the transcription, translation, and
      cortical-rod formation of CRP occur at different phases of oocyte development.
      The endogenous vitellogenic stage is a crucial stage for the initiation of CRP
      and Vg syntheses. The coincidence of these protein syntheses suggests that CRP
      and Vg syntheses are regulated by closely-related mechanisms.

PMID- 15988164
TI  - Molecular cloning of Dmrt1 and its expression in the gonad of Xenopus.
AB  - Sex is determined by various transcription factors in vertebrates. SRY on the Y
      chromosome in mammals has been isolated as the sex-determining gene. In birds,
      Dmrt1 on the Z chromosome of chickens is expressed in the indifferent gonad
      before sex determination. In amphibians, the sex-determining gene is not known
      yet. To examine whether Dmrt1 is expressed during sex determination in Xenopus
      laevis, we first isolated the cDNA, and examined its expression in gonadal
      development by RT-PCR analysis. The expression of Xenopus Dmrt1 (xDmrt1) was
      observed exclusively in the testis amosis. The expression was much higher in the
      testis than in the ovary. This was a pattern different from that in human, mouse,
      and fish such as tilapia and rainbow trout. In addition, the Dmrt1 mRNA was first
      detected in the gonad/mesonephros complex of tadpoles at stage 53, at which time
      the gonads were still indifferent. Taken together, the results suggest that Dmrt1
      may be involved in gonadal differentiation of Xenopus.

PMID- 15988165
TI  - Wnt4 expression in the differentiating gonad of the frog Rana rugosa.
AB  - Wnt4, a member of the Wnt family, is known to influence the sex-determination
      cascade. In mice having a targeted deletion of Wnt4, masculinization occurs in XX
      pups. Therefore, in addition to Sry, Wnt4 is also involved in sex determination
      in mice. In humans, a chromosomal duplication of the WNT4 causes feminization of
      XY-individuals. Thus, for better understanding of the mechanism of sex
      determination in vertebrates, it is necessary to examine the expression of Wnt4
      at early gonadal development stages in non-mammalians. We first isolated the Wnt4
      cDNA from the tetsis of the frog Rana rugosa. R. rugosa Wnt4 had a high
      similarity (>86%) at the amino acid level with zebra fish, chicken, mouse, and
      human Wnt4s. We next employed RT-PCR analysis to examine whether Wnt4 was
      expressed in a sexually dimorphic fashion at early stages of gonadal development
      in R. rugosa. Wnt4 was transcribed first in the embryos at the late gastrula
      stage, and its expression was maintained until the indifferent gonad
      differentiated into a testis or an ovary. Wnt4 expression in the differentiating
      gonad appeared in a non-sexually dimorphic pattern. The results, taken together,
      suggest that Wnt4 is highly conserved through evolution, and that its expression
      in the indifferent gonad takes place with no sexual dimorphism. Thus, Wnt4 is not
      a key factor to initiate the development of a testis or an ovary from the
      indifferent gonads in R. rugosa. However, this gene probably forms part of a
      gonadal-development pathway in this species.

PMID- 15988166
TI  - Sex difference and postnatal change of maternal behavioral patterns in juvenile
      male and female rats.
AB  - Juvenile rats are known to show certain elements of maternal behavior. In this
      experiment, to investigate sex difference and postnatal change of retrieving and
      pup-cleaning (licking) behaviors in juvenile rats, these behaviors were recorded
      using new observation method at 20, 30 and 45 days of age in female and male
      Wistar rats. At 20 days of age, maternal behavior was observed in a common
      plastic observation cage (test A) and then test B was performed. In the test B,
      observation was carried out using a cage with a wooden box that was open on one
      side, helping the juveniles to establish a nest. As the results of day 20, most
      rats in all groups showed licking behavior in both the test A and B. The
      incidence of retrieving behavior increased from the test A to the test B with the
      box in both sexes, especially in males (p<0.01). The box is thought to play a
      facilitative role in induction of retrieving. Moreover, the incidence in males
      was higher than that in females in the test B (p<0.001). At 30 and 45 days of
      age, only a test B with box was performed. The incidences of licking and
      retrieving behaviors at 30 days of age were decreased significantly compared to
      those at 20 days of age in both sexes(p<0.001). Further decrease from 30 days to
      45 days was observed. These results suggest that in juvenile rat, incidence of
      retrieving behavior in males is higher than that in females but there is no sex
      difference in incidence of licking behavior. Potency to show these behaviors
      decreases acutely before puberty in rats.

PMID- 15988167
TI  - Incorporation and utilization of multiple forms of vitellogenin and their
      derivative yolk proteins during vitellogenesis and embryonic development in the
      mosquitofish, Gambusia affinis.
AB  - We previously demonstrated the presence of three forms of vitellogenin (Vg), two
      600 kDa Vgs (600Vg; VgA and VgB) and a 400 kDa Vg (400Vg; phosvitinless Vg) in
      plasma from maturing female viviparous mosquitofish, Gambusia affinis. For
      further quantitative elucidation of the accumulation and utilization of the
      multiple Vg-derived yolk proteins, two sandwich enzyme-linked immunosorbent
      assays (ELISA) were developed using antisera against 600Vgs and a 400 kDa yolk
      protein (400Yp; derived from 400Vg), respectively. Contents of 560 kDa yolk
      protein (560Yp; lipovitellins derived from 600Vg) and 400Yp measured by the
      ELISAs increased in accordance with the growth of vitellogenic oocytes, keeping
      their proportional ratio (mol/mol) at about 4:1. A similar ratio obtained for
      plasma Vgs suggests that the proportional accumulation of the multiple Vg-derived
      yolk proteins is regulated by the hepatic synthesis and secretion of their
      precursor Vgs. When egg homogenate was analyzed by gel chromatography, three
      peaks, consisting of 560Yp, 400Yp and 28 kDa native beta'-component, were
      observed. The elution profile showed no change until embryos reached the early
      neurula stage, however, the relative height of the 560Yp peak as compared to the
      400Yp one decreased after retinal pigmentation. Results from measurements of
      560Yp and 400Yp at each embryonic stage supported the occurrence of unequal
      utilization of the two yolk proteins. The proportional ratios (mol/mol) of 560Yp
      content versus 400Yp content gradually decreased from 4.1 fold in early neurula
      embryo to 1.4 fold in larva just before parturition. The present study thus
      demonstrated unequal utilization of the multiple Vg-derived yolk proteins in
      developing embryos of mosquitofish.

PMID- 15988169
TI  - Airway hyperresponsiveness to methacholine in chemical warfare victims.
AB  - BACKGROUND: The lung is one of the most exposable organs to chemical warfare
      agents such as sulfur mustard gas. Pulmonary complications as a result of this
      gas range from severe bronchial stenosis to mild or no symptoms. Airway
      hyperresponsiveness (AHR) which is usually assessed as response to inhaled
      methacholine is the most characteristic feature of asthma. AHR is reported in
      chronic obstructive pulmonary disease patients and smokers, and may also show in
      chemical warfare victims. However, there are little reports regarding AHR in
      chemical warfare victims. OBJECTIVE: Therefore, in this study, airway
      responsiveness to methacholine in victims of chemical warfare was examined.
      METHODS: The threshold concentrations of inhaled methacholine required for a 20%
      change in forced expiratory flow in 1 s (FEV1; PC20) or a 35% change in specific
      airway conductance (PC35) were measured in 15 chemical war victims and 15 normal
      control subjects. RESULTS: In 10 out of 15 chemical warfare victims (two thirds),
      PC20 and PC35 methacholine could be measured and subjects were called responders.
      AHR to methacholine in responder chemical war victims (PC20 = 0.41 and PC35 =
      0.82 g/l) was significantly lower than in normal subjects (PC20 = 5.69 and PC35 =
      4.60 g/l, p < 0.001 for both cases). There was a significant correlation between
      FEV1 and PC20 methacholine (r = 0.688, p < 0.001). The correlations between PC20
      and PC35 were statistically significant as well (r = 0.856, p < 0.001).
      CONCLUSION: Results showed increased airway responsiveness of most chemical
      warfare victims to methacholine which correlated with the FEV1 value and which
      may be related to chronic airway inflammation or irreversible airway changes.

PMID- 15988170
TI  - The association of pulmonary lymphangioleiomyomatosis with renal and hepatic
      angiomyolipomas in a prepubertal girl: a previously unreported entity.
AB  - Pulmonary lymphangioleiomyomatosis (PLAM) is a rare, diffuse progressive
      interstitial lung disease that affects females of childbearing age and is
      characterized by diffuse proliferation of abnormal smooth muscle fibers
      predominantly developing in the lung and leading to cystic destruction. A
      prepubertal 13-year-old girl with PLAM associated with renal and hepatic
      angiomyolipomas who was treated by nephroureterectomy and thoracoscopic
      pleurodesis is presented. To the best of our knowledge, this is the first
      reported case of PLAM associated with renal and hepatic angiomyolipomas at the
      prepubertal age. After evaluating the clinicopathologic features of this rare
      entity, the authors conclude that PLAM should be considered in the differential
      diagnosis of cystic pulmonary pathologies in children, particularly teenagers.
      The most important clinical aid is to bear this rare entity in mind when a child
      presents with renal and/or hepatic angiomyolipomas. Thoracoscopic pleurodesis is
      the most effective treatment modality for recurrent pneumothoraces.

PMID- 15988172
TI  - Evaluation of a portable recording device (Reggie) with actimeter and
      nasopharyngeal/esophagus catheter incorporated.
AB  - BACKGROUND: Portable recording devices without electroencephalogram recordings
      are frequently used for diagnosis of sleep-disordered breathing. However, an
      exact measure of sleep is important, since the diagnosis is based on the average
      number of events per hour of sleep, the apnea/hypopnea index (AHI). Actimetry is
      a simplified method for distinguishing sleep and wakefulness by measurements of
      activity. OBJECTIVES: In this study, recording with a portable recording device
      (Reggie) including an incorporated actimeter and polysomnography were done
      simultaneously in order to test the effect of the actimeter. METHODS: The study
      was performed at the sleep-related breathing disorder unit at the Ullevaal
      University Hospital, Oslo, Norway. Fifty-two consecutive patients referred to the
      hospital for diagnosis of sleep-disordered breathing were included. RESULTS:
      There is agreement between the AHI obtained from the polysomnography and the AHI
      obtained from the Reggie system. The estimated mean difference is 3.5, with an SD
      of 5.3 (r = 0.98). The sleep time calculated with the Reggie system is greater
      than the sleep time obtained by polysomnography, the mean difference being 46
      min, SD 56 min (r = 0.45). CONCLUSIONS: Sleep time calculations with the Reggie
      system overestimate the sleep time. Still, the AHIs obtained by the two systems
      show good agreement. There is a slight tendency for the Reggie system to provide
      an AHI which is too low. This difference is small, and in most cases, it will be
      of no clinical significance.

PMID- 15988187
TI  - Liposomes: a new way to deliver pain medications.

PMID- 15988189
TI  - Skin flora: unwanted dead or alive.

PMID- 15988188
TI  - Caring for a patient having a miscarriage.

PMID- 15988190
TI  - Administering medication by the Z-track method.

PMID- 15988171
TI  - Inflammatory response to sputum induction measured by exhaled markers.
AB  - BACKGROUND: Sputum induction is increasingly used to study both cellular and
      biochemical composition of the airways. However, there is a significant rise in
      the percentage of neutrophils at 8 h after inhalation with hypertonic saline.
      OBJECTIVE: The aim of this study was to assess whether markers of inflammation in
      exhaled air and exhaled air condensate change after sputum induction in normal
      and asthmatic subjects. METHODS: We measured leukotriene B(4) (LTB(4)) and a
      marker of oxidative stress, 8-isoprostane, (by enzyme immunoassay) in exhaled air
      condensate and exhaled nitric oxide (NO; by chemiluminescence analyzer) in 15
      healthy subjects (8 females, mean age 35 +/- 4 years, FEV(1) 97.4% predicted) and
      in 8 mild asthmatic subjects (5 males, mean age 34 +/- 2 years, FEV(1) 70.5%
      predicted). RESULTS: LTB(4) was significantly higher compared with baseline at 6
      h but did not remain increased at 24 h after sputum induction (134.3 +/- 30.15
      and 75.4 +/- 14.32 vs. 64.6 +/- 11.6 pg/ml at baseline; p < 0.02 and p > 0.05,
      respectively) in healthy subjects. An inverse correlation between LTB(4) and
      exhaled NO at 6 h after sputum induction was observed in healthy subjects (r = 
      0.66, p < 0.03). No increase in LTB(4) levels was observed in asthmatic patients.
      Baseline 8-isoprostane levels were higher in asthmatic patients than in healthy
      subjects (47.3 +/- 37.1 vs. 17.5 +/- 8.8 pg/ml; p < 0.01). A trend towards
      increased levels of 8-isoprostane could be observed at 6 and 24 h after
      inhalation in healthy subjects (26.2 +/- 3.7 and 26.7 +/- 3.9 pg/ml; p = 0.09 and
      p = 0.07, respectively). In healthy subjects, exhaled NO was significantly higher
      compared with baseline at 6 h and remained increased 24 h after sputum induction
      (7.96 +/- 3.5 vs. 5.61 +/- 1.86 ppb; p < 0.01 and p < 0.05, respectively).
      Exhaled NO levels were increased in asthmatic patients but did not further
      increase after sputum induction. CONCLUSIONS: Sputum induction with hypertonic
      saline causes an inflammatory response which should be considered when using the
      technique to monitor airway inflammation.

PMID- 15988194
TI  - Documenting peripheral I.V. therapy.

PMID- 15988191
TI  - Keep a close eye on vacuum-assisted wound closure.

PMID- 15988195
TI  - What causes celiac disease?

PMID- 15988217
TI  - What Ruth knew.
AB  - My patient had been uncommunicative for years before coming to our nursing home
      for daytime care. Could I help her now?

PMID- 15988215
TI  - Clearing away pulmonary secretions.
AB  - Excess or retained pulmonary secretions impair ventilation, invite infection, and
      may threaten survival. Find out who's at greatest risk and how to keep airways
      clear.

PMID- 15988218
TI  - Clear the air with closed suctioning.
AB  - Using a closed system to remove airway secretions helps protect your patient and
      yourself.

PMID- 15988219
TI  - Why not nursing.
AB  - Does nursing have an image problem that scares off potential nursing students?
      Here's what high-school students and adult career-switchers think about nursing
      as a potential career choice.

PMID- 15988220
TI  - Helping parents reduce the risk of SIDS.
AB  - Sudden infant death syndrome can strike without warning, but some babies are more
      vulnerable than others. Learn what you can do to minimize the danger.

PMID- 15988221
TI  - Patient-education guide: sudden infant death syndrome (SIDS).

PMID- 15988222
TI  - Canine units: the softer side of security.
AB  - Try a different breed of security officer to improve safety and boost morale in
      your facility.

PMID- 15988223
TI  - Looking at lymphoma and leukemia.
AB  - Learn the signs and symptoms of these liquid tumors and how to help patients
      manage them.

PMID- 15988229
TI  - Bulletin boards: not just for kids anymore.

PMID- 15988231
TI  - Identifying infection in chronic wounds.

PMID- 15988232
TI  - . . . About hypercalcemia.

PMID- 15988233
TI  - Yellow fever.

PMID- 15988236
TI  - Pacemaker malfunction.

PMID- 15988237
TI  - Indications and rationale for use of vascularized fibula bone flaps in cervical
      spine arthrodeses.
AB  - BACKGROUND: Anterior cervical spine arthrodesis for large defects using autograft
      or allograft fibula for anterior structural support is a widely accepted
      procedure. In unique demand situations, a vascularized fibular flap is regarded
      as an "improvement" to the standard procedure. While a vascularized flap does
      deliver living tissue to the region, it does so with added potential morbidity
      and increased technical demand. The indications in the literature for this
      procedure have not been clearly defined. In this article, the authors review
      specific high-demand situations where they believe a vascularized flap is
      indicated. They also review patient outcomes after this procedure. METHODS:
      Fibular free flaps were used in six patients with failed previous cervical spine
      arthrodeses. Three of the six patients had preoperative radiation therapy, and
      one received postoperative radiation treatment. All six patients had tumor and/or
      osteomyelitis present. RESULTS: One patient died of intraoperative hypotension 3
      days after a successful free flap transfer during an elective posterior spine
      instrumentation procedure. One flap was lost from a venous thrombosis, and the
      patient was then treated successfully with a second fibular free flap. Clinical
      and radio-graphic evidence of fusion was obtained at 3 months in the five
      surviving patients, and neurologic function remained stable or improved.
      CONCLUSIONS: Analyzing their results and the literature, the authors propose that
      fibular free flaps are indeed a useful adjunct in difficult cervical spine
      stabilization procedures. Indications for this flap include combinations of the
      following situations: failed prior attempts at fusion, anterior cervical
      arthrodeses of three or more vertebral levels, osteomyelitis of the spine, and
      tumor cases when the spine has been or will be radiated.

PMID- 15988238
TI  - Microphthalmia and synostotic frontal plagiocephaly: a rare clinical entity with
      implications for craniofacial reconstruction.

PMID- 15988239
TI  - Management of superficial leiomyosarcoma: a retrospective study of 10 cases.
AB  - BACKGROUND: Superficial leiomyosarcoma is a rare soft-tissue tumor. Management of
      this tumor, including pathological evaluations and therapies, is not clearly
      defined in the existing literature. METHODS: Ten patients with superficial
      leiomyosarcoma treated in our institutes were recalled and scheduled for
      examination. Assessments were carried out according to clinical characteristics,
      therapies used, histological grade (based on the grading system of the Federation
      Nationale des Centres de Lutte Contre Le Cancer), tumor-node-metastasis stage
      (using the American Joint Committee on Cancer staging system), recurrences rates,
      state of metastases, and the current condition of each patient. RESULTS: No local
      recurrences or distant metastases were seen in eight patients with low-grade and
      early-stage disease, whereas two patients with high-grade and advanced-stage
      disease had recurrence and one of these two patients died of the disease.
      CONCLUSIONS: This study indicates that evaluations using the Federation Nationale
      des Centres de Lutte Contre Le Cancer grading system and the American Joint
      Committee on Cancer tumor staging system were useful. The authors advocate that
      surgical treatment of low-grade cutaneous leiomyosarcoma by complete excision
      with a narrow margin is adequate. For low-grade and early-state subcutaneous or
      soft-tissue leiomyosarcoma, wide excision with a minimum 2-cm lateral margin and
      one-tissue barrier deep margin is recommended. Management of high-grade
      leiomyosarcomas is still difficult; adequate wide excision may be the only
      option.

PMID- 15988240
TI  - Unusual etiology of simultaneous deep space hand infection and necrotizing
      fasciitis of the foot.

PMID- 15988241
TI  - "Keystone" approach for intracranial nasofrontal dermoid sinuses.
AB  - Nasofrontal dermoid sinus tracts that extend intracranially through the foramen
      cecum or ethmoid can be difficult to completely resect. Complete extirpation of
      nasofrontal dermoid sinus cysts is essential for effective treatment of this
      problem to minimize the chance of recurrence. The authors describe a new
      technique based on parasagittal osteotomies through the supraorbital bar, or
      bandeau, that ensures that the resection of the nasofrontal dermoid sinus cysts
      is complete. This technique also limits the size of the external nasal incision
      and enhances the surgeon's exposure of the anterior cranial base for resection of
      intradural extension. This approach also enhances exposure for the direct repair
      of the dura and the cranial vault.

PMID- 15988242
TI  - The pediatric mandible: I. A primer on growth and development.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe embryonic and fetal mandibular development. 2. Summarize the
      aggregate changes in mandibular form from birth to puberty. 3. Describe the
      eruption and maturation of the deciduous and permanent mandibular dentition.
      BACKGROUND: In this, the first of two articles addressing the surgical management
      of pediatric mandibular fractures, the authors provide a detailed discussion of
      mandibular development and anatomy during the fetal period, infancy, and
      childhood. METHODS: A review of the pertinent literature was performed. The
      changing structure of the developing mandible is discussed, with particular
      attention to surgically relevant anatomical structures. RESULTS: Throughout
      development, key anatomical structures with relevance to surgical therapy change
      markedly in position. The mandible undergoes significant change in its bony
      structure and the composition of its surrounding soft tissues. The mandible's
      bony structure becomes more robust, with an increasingly acute gonial angle and
      enlargement of the ramus and body. Furthermore, the mandible provides the bony
      structure from which tooth buds erupt as the deciduous and permanent dentition--a
      process that generates significant growth of the alveolar process. As a
      consequence, the distance between the developing dentition and the inferior
      mandibular border increases. While the canal of the inferior alveolar nerve
      undergoes significant superior displacement, the mental foramen becomes
      positioned more posteriorly over time. In addition, the ligamentous and muscular
      attachments that surround the temporomandibular joint become increasingly robust.
      Throughout childhood and adolescence, the blood supply of the mandibular body
      changes little, with the buccal periosteal plexus and inferior dental artery
      making significant contributions. CONCLUSIONS: Mandibular growth provides the
      basis for normal occlusal relations and the generation of increasingly large
      masticatory force. Although the exact mechanisms of bone remodeling during
      mandibular development remain unclear, the process likely receives contributions
      from primary growth centers and the response to local alterations in
      biomechanical force produced by surrounding soft-tissue structures. A working
      knowledge of the changing mandibular anatomy is a prerequisite for effective
      clinical management of traumatic injury.

PMID- 15988243
TI  - Autogenous fascia lata grafts: clinical applications in reanimation of the
      totally or partially paralyzed face.
AB  - BACKGROUND: Although they are traditionally reserved for "aesthetic refinement"
      in the latter stages of facial reanimation surgery, the author uses a variety of
      autogenous fascia lata grafts in a very aggressive approach as the primary
      therapeutic option in static facial rebalancing and/or in conjunction with
      dynamic muscle transfers to achieve architectural integrity and functional
      restoration of the totally or partially paralyzed face. METHODS: Forty-nine
      autogenous fascia lata grafts, harvested through serial incisions in the lateral
      thigh, were placed in 35 totally or partially paralyzed faces. The grafts were
      categorized by anatomical location: I and II, lateral lip in totally paralyzed
      and partially paralyzed faces, respectively; III, nostril suspension; IV, lower
      eyelid suspension; V, bimalar lower lip sling; and VI, platysma
      transfer/autogenous fascia lata extension for lower lip invagination. RESULTS: In
      all group I and II cases, static balance of facial architecture was restored at 4
      to 6 weeks (after swelling resolved). Average lip commissure displacement was
      corrected to within 0.5 cm of the horizontal axis. Subjective functional
      improvement in speech, fluid retention, and chewing was immediate in all cases.
      In group I (n = 10; median age, 10.5 years), a 60 to 100 percent symmetrical
      smile was achieved with voluntary gracilis contraction of 3 of 5 to 5 of 5. In
      group II (n = 20; median age, 33 years), with 16 sling only patients, one to two
      grades of voluntary risorius and lip elevator motion were achieved in most. When
      accompanied by a temporalis turnover flap, both risorius and lip elevator
      function improved two to three grades. In group III (n = 5), inspiratory collapse
      was ameliorated in all cases and nasal flow improved subjectively 80 to 100
      percent. In group IV (n = 4), scleral show and keratitis were improved in all
      cases. In group V (n = 6), improved oral competence was achieved in all patients.
      In group VI (n = 4), static lip evagination was achieved in all cases; voluntary
      lip depressor function was two to four grades improved. CONCLUSIONS: Early
      placement of autogenous fascia lata restores static balance of the deeper facial
      architecture in repose. Functional improvement of chewing, fluid retention,
      speech articulation, smile symmetry, and ectropion is immediate. The
      psychological effect is also immediate, with achievement of self-esteem and
      acceptance by family and peers.

PMID- 15988245
TI  - Botulinum toxin for aberrant facial nerve regeneration: double-blind, placebo
      controlled trial using subjective endpoints.
AB  - BACKGROUND: Aberrant facial nerve regeneration syndrome is systematically studied
      by constructing a subjective questionnaire organized into pertinent domains
      (impairment of quality of life, social interactions, perception of self
      appearance, visual function, and perception of problem severity) and by physical
      assessment of degree of involuntary palpebral fissure closure during routine
      facial movements using videotaping and a physicians' grading scale. METHODS: The
      videotape measurements of corneal light reflex to upper lid margin distance and
      vertical palpebral distance were made during adynamic and active facial
      expression. Thirty-six patients were studied (six in an open-label pilot study
      design and 30 in a multicenter, double-blind, placebo-controlled trial).
      Botulinum toxin type A injections consistently suppressed the degree of
      involuntary eyelid movement associated with smiling, chewing, and puckering by
      each measurement and in both study designs. RESULTS: In all subjective morbidity
      domains, improvement was demonstrated in the double-blind study design (quality
      of life, p < 0.05; social interaction, p < 0.001; personal appearance, p < 0.001;
      peripheral visual impairment, p < 0.01; and perception of severity, p < 0.05).
      Correlation between degrees of physical impairment was significant but low
      comparing degree of subjective impairment to direct videotaped measurements.
      Correlation was more significant comparing subjective scores to the physicians'
      grading scale assessment of degree of physical impairment. CONCLUSIONS:
      Impairment in quality of life, social interactions, and self-assessment of
      appearance closely reflected the nature of the morbidity associated with
      palpebral fissure asymmetry associated with aberrant facial nerve regeneration.
      The physicians' grading scale best reflected subjective morbidity over direct
      videotaped measurements.

PMID- 15988246
TI  - Five-year experience with the transoral endoscopically assisted treatment of
      displaced condylar mandible fractures.
AB  - BACKGROUND: From April of 1998 to May of 2003, the minimally invasive transoral
      approach for endoscopically assisted reduction and osteosynthesis of 62 displaced
      condylar mandible fractures was performed in 58 patients. METHODS: By means of
      limited transoral incision, the endoscopically assisted reduction and fixation of
      condylar fractures was performed using 30- and 45-degree angled endoscopes.
      Twenty-five fractures were condylar and 37 were subcondylar. The condylar neck of
      the proximal fragment was displaced medially in 17 fractures and laterally in 45
      fractures. Four patients presented bilateral condylar mandible fractures. Using
      angled endoscopes, good visibility of the fracture site was obtained, which
      allowed for precise anatomical reduction in all patients. An angulated drill and
      screwdriver facilitated miniplate fixation by means of the transoral approach.
      The mean operating time was measured in the last 30 consecutive cases: 1 hour 5
      minutes. RESULTS: Postoperatively, all patients showed quick recovery to
      preinjury occlusion. Normal temporomandibular joint function was noted 6 months
      after surgery in all patients. CONCLUSIONS: The transoral endoscopically assisted
      treatment using an angulated drill and screwdriver is the method of choice for
      surgical management of displaced condylar fractures, even in fractures with
      medial override. Facial nerve injury and visible scars are avoided by using the
      transoral approach.

PMID- 15988247
TI  - Internal midface distraction in correction of severe maxillary hypoplasia
      secondary to cleft lip and palate.
AB  - BACKGROUND: Maxillary hypoplasia is a familiar deformity in patients with cleft
      lip and palate. A large amount of maxilla advancement is often needed to correct
      the severe deformity, but local soft-tissue scars around the maxilla restrict
      maxilla advancement and increase the relapse rate. By gradually lengthening both
      the bones and the soft tissues, midface distraction can greatly increase
      postoperative stability and lower the relapse rate. METHODS: Ten patients with
      severe maxillary hypoplasia secondary to cleft lip and palate were treated with
      midface distraction using three kinds of internal distraction devices. Among
      them, six patients received an alveolar bone graft from the iliac crest during
      their Le Fort I osteotomy, and a bilateral sagittal split ramus osteotomy was
      performed simultaneously to push back the mandible in five patients with
      prognathia, to obtain a normal soft-tissue profile and occlusal relationship.
      RESULTS: Successful maxillary advancements ranging from 5 to 15 mm were measured
      from preoperative and postoperative cephalograms. Patients' sella-nasion-point A
      angles increased from an average of 71.25 degrees preoperatively to 79.05 degrees
      postoperatively. Orthodontic therapies were adopted before and/or after midface
      distraction. After the consolidation period, dense new bone was found to have
      formed in the distraction gap. During the follow-up period, the position of the
      maxilla and the final occlusal relationship were stable and acceptable, and no
      obvious relapses were seen. CONCLUSION: Midface distraction is an ideal choice
      for the correction of severe maxillary hypoplasia secondary to cleft lip and/or
      palate.

PMID- 15988248
TI  - Unilateral cleft lip repair: an anatomical subunit approximation technique.
AB  - BACKGROUND: A technique of unilateral cleft lip repair is described. The repair
      draws from a variety of previously described repairs and adheres to a concept of
      anatomical subunits of the lip. Cases from within the spectrum of the deformity
      have been chosen from a series of 144 consecutive cases to demonstrate the
      applicability of the technique in all forms of unilateral cleft lip. METHODS:
      Incisions cross the lip perpendicular to the cutaneous roll at the cleft side
      peak of Cupid's bow of the medial lip and at the base of the philtral column of
      the lateral lip. Above this level, incisions ascend the lip to allow for
      approximation along a line symmetrical with the non-cleft-side philtral column.
      Incisions then ascend superolaterally bordering the lip columellar crease to the
      point of closure in the nostril sill. A Rose-Thompson lengthening effect occurs
      just above the level of the cutaneous roll. If necessary, a small triangle
      positioned just above the cutaneous roll is often used. Any central vermilion
      deficiency is augmented by a laterally based triangular vermilion flap from the
      lateral lip element. RESULTS: Since January of 2000, this technique has been used
      in 144 consecutive unilateral cleft lip repairs. The inferior triangle is small
      (average, 1.24 mm; range, 0 to 2 mm). The technique can be applied to all degrees
      of unilateral cleft lip. CONCLUSIONS: A technique of unilateral cleft lip repair
      is described. The repair allows for a repair line that ascends the lip at the
      seams of anatomical subunits.

PMID- 15988249
TI  - Furlow palatoplasty for management of velopharyngeal insufficiency: a prospective
      study of 148 consecutive patients.
AB  - BACKGROUND: The objectives of the study were to describe speech outcomes in a
      large series of patients undergoing Furlow palatoplasty for management of
      velopharyngeal insufficiency and to test whether preoperative velopharyngeal gap
      size and other patient characteristics significantly affect those outcomes.
      METHODS: Data collected included age at the time of surgery, surgeon, type of
      cleft, syndrome diagnosis, preoperative velopharyngeal gap size as determined by
      videonasendoscopy, and preoperative and postoperative perceptual speech
      assessments. Descriptive statistics were generated and ordinal logistic
      regression on the outcome variable, postoperative velopharyngeal insufficiency
      severity score, was performed. RESULTS: In this series of 154 patients, 148 had
      complete perceptual speech data. Of these 148 patients, 72 percent had
      improvement in velopharyngeal insufficiency severity after the procedure and 56
      percent had complete resolution of velopharyngeal insufficiency. Postoperative
      insufficiency was scored as none or minimal (i.e., resolution) in 38 of 52
      patients (73 percent) with a small preoperative velopharyngeal gap, 26 of 51
      patients (51 percent) with a moderate preoperative gap, and four of 21 patients
      (19 percent) with a large preoperative gap. Preoperative velopharyngeal gap size
      was significantly associated (p < 0.0001) with postoperative insufficiency on
      ordinal multivariate logistic regression after controlling for preoperative
      insufficiency and other covariates. There was not a significant association
      between syndrome diagnosis, age at Furlow palatoplasty (younger than 5 years
      versus older), gender, surgeon, or presence of submucous cleft palate and
      postoperative speech outcome, in either the unadjusted or adjusted analyses.
      CONCLUSIONS: Preoperative velopharyngeal gap size, as determined with
      nasendoscopy, was significantly associated with postoperative velopharyngeal
      insufficiency severity after Furlow palatoplasty. Small gap size is associated
      with a greater likelihood of resolution.

PMID- 15988251
TI  - The correction of velopharyngeal insufficiency by Furlow palatoplasty in patients
      older than 3 years undergoing Veau-Wardill-Kilner palatoplasty: a prospective
      clinical study.
AB  - BACKGROUND: Velopharyngeal insufficiency may persist after primary repair of the
      palate. This insufficiency causes a speech deficit. Although there are many
      treatment alternatives, the most effective treatment of velopharyngeal
      insufficiency remains controversial. METHODS: The authors performed Furlow
      palatoplasty in patients older than 3 years who had undergone primary
      palatoplasty with the Veau-Wardill-Kilner technique. Speech was assessed by a
      speech therapist before and after the operation. Velopharyngeal closure and velum
      motion were recorded using a video nasendoscope before and also 12 months after
      the operation. Any increase in velum length was measured. RESULTS: After Furlow
      palatoplasty, 10 of 27 patients (37 percent) made complete recovery and 12 (44
      percent) made substantial recovery from hypernasal resonance, but five (18.5
      percent) showed no improvement. Regarding nasal emission, 16 of 27 patients (59.3
      percent) made complete and eight (29.6 percent) made substantial recovery, but
      there was no change in three (11 percent). Five of 27 patients (18.5 percent)
      achieved complete intelligibility and 18 of 27 (66.7 percent) improved
      intelligibility, but four (14.8 percent) did not show any improvement in
      intelligibility. Articulation improved considerably in 17 of 27 (63 percent). The
      overall rate of surgical success and near misses who benefited from the surgery
      was 18 of 27 (67 percent), and a positive correlation between surgical success
      and articulation and intelligibility was noticed. Video nasendoscopy showed
      complete velopharyngeal closure in 15 of 27 patients (56 percent). The mean velar
      length increased by 44 percent. After secondary Furlow palatoplasty, patients
      with small gaps benefited more. CONCLUSIONS: The results suggest that Furlow
      palatoplasty performed in later years improves not only speech but also
      velopharyngeal closure by reorienting the levator veli palatini muscle and
      augmenting the velum.

PMID- 15988253
TI  - Application and refinement of the superior gluteal artery perforator free flap
      for bilateral simultaneous breast reconstruction.
AB  - BACKGROUND: The gluteal artery perforator free flap represents the state of the
      art in autogenous breast reconstruction for the patient with insufficient
      abdominal donor tissue. Preservation of the gluteal musculature limits morbidity
      and allows for rapid patient recovery. The need for intraoperative repositioning
      has historically limited gluteal artery perforator flap breast reconstruction to
      one breast per operation. This results from a desire to avoid marathon surgical
      times when the flaps are dissected out sequentially and/or having the patient lie
      on the first reconstructed breast as the second flap is harvested. Prior
      protocols have relied on staging the reconstructions weeks apart to address these
      concerns. This is a significant issue for patients requiring bilateral mastectomy
      and results in the patient being subjected to two major sequential operations and
      their associated recoveries. METHODS: The authors describe their experience and
      associated technical considerations with an initial 20 patients (40 flaps).
      RESULTS: The average operative time was 7 hours 47 minutes (excluding
      mastectomy). There were no vascular complications and no flap failures.
      CONCLUSIONS: Bilateral simultaneous gluteal artery perforator flap breast
      reconstruction may be performed safely with reproducible success and a
      complication rate that is comparable to that of other commonly performed
      autogenous tissue techniques. This report represents the largest described
      experience to date and the first dedicated treatise on a protocol that provides
      significant advantages and an option that has heretofore been unavailable to this
      group of patients.

PMID- 15988255
TI  - Analyzing the vascular architecture of the free TRAM flap using intraoperative ex
      vivo angiography.
AB  - BACKGROUND: Using ex vivo intraoperative angiography to analyze 14 flaps from 12
      breast reconstruction patients, the authors investigated the vascular
      architecture of free transverse rectus abdominis musculocutaneous (TRAM) flaps
      nourished by the deep inferior epigastric artery. METHODS: Contrast medium was
      injected through the deep inferior epigastric artery and flaps were radiographed
      to observe their vascular patterns. RESULTS: TRAM flaps showed one or two
      segmental arteries stained on their ipsilateral side (zones 1 and 3) and serving
      as the flap's axial artery. These segmental arteries directly connect to the
      large perforators (axial perforators) and emerge not only from the paraumbilical
      perforators but also from the caudal branches of the deep inferior epigastric
      artery. Arterial density is always lower in the contralateral area (zones 2 and
      4) than in the ipsilateral area (zones 1 and 3). CONCLUSIONS: Because the
      cephalic half of zone 2 and all of zone 4 remain unstained, these areas are prone
      to skin or fat necrosis, especially in high-risk patients. Ex vivo angiography,
      by providing specific information about the individual flap and by reflecting its
      flow physiology, enables one to observe and to chart the vascular architecture of
      free TRAM flaps nourished by the deep inferior epigastric artery.

PMID- 15988256
TI  - Unilateral vertical scar breast reduction with glandular transposition of the
      nipple-areola in breast asymmetry.
AB  - BACKGROUND: A unilateral breast reduction procedure to mimic the contralateral
      breast poses a challenge to the plastic surgeon. All aspects of breast aesthetics
      are essential surgical considerations. The authors have used a vertical scar
      technique with glandular transposition of the nipple-areola complex. METHODS: In
      this series of patients, the larger of the asymmetrical breasts was reduced using
      a modified vertical scar breast reduction technique to simulate the shape and
      size of the smaller breast. Thirty-four patients are presented. Preoperative
      marking of the patient was modified to simulate the smaller breast, including
      measurements from the sternal notch to the nipple, to the midline of the
      submammary fold, the base of the breast, and the diameter of the nipple-areola
      complex. The mean resection weight was 282 g (range, 76 to 860 g) and the mean
      follow-up period was 15 months. A glanduloplasty was performed to simulate the
      shape of the contralateral breast. RESULTS: Thirty-one of the 34 patients
      reported that, overall, they were satisfied (91 percent) with the final shape of
      the breasts, symmetry, and the nature of the scars. Three patients were not
      entirely satisfied. Two of these requested further resection and one requested a
      minor scar revision because of persistent wrinkles in the submammary fold.
      CONCLUSIONS: Adequate long-term breast symmetry was achieved as confirmed by a
      high patient satisfaction rate. Unilateral vertical scar breast reduction with
      glandular transposition of the nipple-areola has been a valuable method in
      selected cases of breast asymmetry.

PMID- 15988258
TI  - A prospective study of antibiotic efficacy in preventing infection in reduction
      mammaplasty.
AB  - BACKGROUND: The role of prophylactic antibiotics in reduction mammaplasty remains
      controversial. However, most surgeons choose to use antibiotics. In addition to
      cost and potential allergic reactions, unnecessary administration of antibiotics
      can suppress host natural flora and produce resistant organisms. METHODS: Fifty
      patients were sequentially assigned to one of three study limbs: (1) no
      antibiotics, (2) preoperative antibiotics only, or (3) preoperative and
      postoperative antibiotics. The study was designed to include approximately 17
      patients in each group. Cephalosporin antibiotics were used unless there was any
      question of allergy, in which case an alternative antibiotic regimen was used.
      Preoperative data collected on patients included age, body mass index, history of
      diabetes mellitus, peripheral vascular disease, previous breast surgery, steroid
      therapy, and tobacco use. Operative data included specimen weight, operative
      time, estimated blood loss, prolonged intraoperative hypotension, adjunctive
      axillary and breast tail liposuction, and intraoperative breast tissue culture.
      RESULTS: The patient population in the three limbs of the study was similar.
      Thus, there was no significant difference among the groups insofar as the
      preoperative data were concerned (p > 0.20): age, body mass index, diabetes
      mellitus, peripheral vascular disease, previous breast surgery, and steroid or
      tobacco use. Furthermore, no significant difference (p > 0.12) was noted among
      intraoperative data in the three groups: specimen weight, operative time,
      estimated blood loss, prolonged hypotension, adjunctive breast liposuction, and
      positive bacterial culture from intraoperative breast tissue samples. Ninety
      percent of positive intraoperative breast tissue cultures revealed Staphylococcus
      epidermidis. Using strict criteria, the infection rate ranged from 19 to 20
      percent. There was no significant difference (p > 0.91) in rate of infection
      among the three study limbs. There was, however, a significant reduction (p =
      0.002) in delayed wound healing in the group that received preoperative
      antibiotics only. Among the studied risk factors for infection, only positive
      intraoperative culture of breast tissue was significant (p = 0.008) for
      development of infection. There was a significant association between delayed
      wound healing and infection (p = 0.003). CONCLUSIONS: This prospective study did
      not find that prophylactic antibiotics in reduction mammaplasty have an effect on
      infection; however, a single preoperative dose significantly improved wound
      healing.

PMID- 15988259
TI  - Surgical strategy for infant obstetrical brachial plexus palsy: experiences at
      Chang Gung Memorial Hospital.
AB  - BACKGROUND: Strategies for management of infant obstetrical brachial plexus palsy
      remain controversial, including timing of surgery and treatment modalities.
      METHODS: The senior author (Chuang) performed surgical explorations on 78 infant
      obstetrical brachial plexus palsy patients from 1992 to 1999. Sixty-eight
      patients underwent brachial plexus operation during the infant period (2 to 11
      months), and 10 patients underwent surgery beyond the infant period. RESULTS: For
      the ruptured upper and/or middle trunk injury (Erb's palsy), better shoulder and
      elbow function was observed in those who received numerous short grafts from C5
      to the suprascapular and posterior division and from the C6 spinal nerve to the
      anterior division of the upper trunk. For the rupture injury associated with root
      avulsion (total palsy), nerve graft and transfer (intraplexus and extraplexus)
      provided a one-stage reconstruction for shoulder, elbow, and especially hand
      functions. The contralateral C7 or ipsilateral part of the ulnar nerve transfer
      was rarely used in infant obstetrical brachial plexus palsy, compared with adult
      brachial plexus injury. CONCLUSIONS: The operative results proved that earlier
      timing of nerve surgery (within 3 months) is strongly indicated in patients who
      have total palsy, and only relatively indicated in patients with isolated rupture
      of the upper plexus.

PMID- 15988262
TI  - Complications after Pi Plate osteosynthesis.
AB  - BACKGROUND: Distal intraarticular radius fractures can be operated on by means of
      a palmar or dorsal approach. The dorsal approach has been reported as a treatment
      option that often leads to tendon ruptures. The purpose of this study was to show
      that a dorsal implant does not lead to a high rate of tendon ruptures. METHODS: A
      retrospective study was conducted in which the patient population was analyzed
      for complaints and complications, follow-up time, and further surgical
      procedures. RESULTS: A series of 389 patients with distal intraarticular
      fractures of the radius treated with the dorsal Pi Plate is reported. There was a
      complication rate of 6.7 percent within the first 2 postoperative months. A
      special focus was on the occurrence of extensor tendon ruptures, which occurred
      in five cases in the patient population. This most feared complication occurred
      within the first 8 months after surgery and in no case at a later stage. All
      tendon ruptures were reconstructed and healed without further complications.
      Hardware was removed in 75.5 percent of patients after 6 to 8 months. In the
      remaining 24.5 percent of patients, the plates were left in situ for more than 33
      months, and 89 percent of these patients were free of pain and had excellent
      movement in the wrist. CONCLUSIONS: The authors conclude that the Pi Plate is a
      very good surgical option, especially in complicated, comminuted fractures
      classified as C3. It is not associated with an overly high risk of extensor
      tendon ruptures, as has been suggested by other authors.

PMID- 15988261
TI  - Biceps femoris perforator free flap for upper extremity reconstruction:
      anatomical study and clinical series.
AB  - BACKGROUND: Perforator flaps are an important development in reconstructive
      surgery. The description of new perforator flaps is an open field in anatomical
      and surgical research. METHODS: The anatomy of the musculocutaneous perforating
      vessels of the short head of the biceps femoris muscle was investigated as a
      possible source for free tissue transfer in 10 fresh specimens. A series of 10
      free biceps femoris perforator flaps for upper extremity reconstruction is
      described. RESULTS: There were three constant sizable perforators, located at 6
      cm (range, 5 to 6.5 cm), 11.6 cm (range, 10 to 14 cm), and 15.3 cm (range, 14 to
      17 cm), respectively, from the knee joint line. The distalmost perforator was a
      branch off the superior lateral genicular artery in all anatomical specimens. The
      middle perforator was a direct branch off the popliteal artery in 60 percent of
      the cases and off the profunda femoris in the remaining 40 percent. The uppermost
      perforator was usually a branch off the middle perforator. The flaps of the
      clinical series were based on the middle perforator (11.6 cm). All 10 free flaps
      were used for upper extremity trauma coverage, with a 100 percent success rate,
      although one flap required pedicle revision because of arterial thrombosis and
      developed partial necrosis. Donor-site delayed wound healing occurred in two
      patients. CONCLUSIONS: The vascular anatomy is relatively constant. Flap
      dissection is straightforward under tourniquet control, donor morbidity is low
      provided a primary closure is possible, and pedicle size is appropriate for
      repair. When a moderate-size free flap with moderate thickness and a medium-sized
      pedicle is needed, the biceps femoris perforator flap should be considered in the
      first-choice group of donor areas.

PMID- 15988263
TI  - Free perforator flaps in children.
AB  - BACKGROUND: Raising perforator flaps is said to be a tedious procedure. The
      benefits, however, are great. In adults, perforator flaps have proved their
      usefulness and reliability in various clinical situations. In children, donor
      sites for free flaps are particularly scarce because of the need for a long and
      reliable vascular pedicle of sufficient size. There is also the need to minimize
      donor-site morbidity from aesthetic, functional, and psychological perspectives.
      METHODS: The authors present a series of 23 consecutive free perforator flaps
      performed by the first author in 20 children; ages at the time of operation
      ranged from premature (born at 28 weeks) to 16 years (mean age, 7 years 5
      months). Three children presented with upper limb defects; the remaining 17
      children sustained major soft-tissue defects of the lower limb. All the lesions
      necessitated extensive coverage with a free flap. Flaps used in this series
      included nine deep inferior epigastric artery perforator flaps, seven
      thoracodorsal artery perforator flaps, and seven compound ("chimera")
      thoracodorsal artery perforator flaps. RESULTS: All flaps but one were
      successful. With a follow-up of up to 7 years, the results in this series compare
      favorably with those of perforator flaps in adults or pediatric free flaps in the
      literature. CONCLUSIONS: In children, as in adults, perforator flaps are a
      valuable alternative to the traditional muscle or myocutaneous free flap. Because
      of the added advantage of reducing donor-site morbidity, perforator flaps have
      become the authors' preferred option in reconstructive cases in children.

PMID- 15988264
TI  - Bone exposure in the leg: is a free muscle flap mandatory?
AB  - BACKGROUND: In lower leg defects with bone, hardware, or articular exposure, a
      free tissue transfer is often the only valuable option. However, in well-selected
      clinical cases, pedicled flaps are still indicated because they provide an
      alternative for the more demanding and risky microsurgical procedure. The medial
      adipose-fascial flap of the leg represents an ideal local regional fascial flap.
      METHODS: Twenty-two medial adipose-fascial flaps (performed in 21 patients) were
      reviewed retrospectively and compared with a series of 22 free gracilis flaps (22
      patients) selected out of 150 muscular free flaps for lower leg reconstruction.
      All patients with defects larger than 40 cm, peripheral vascular disease, deep
      defects, and osteomyelitis were excluded in order to obtain the same surgical
      indications in which the local medial adipose-fascial flap could have been used.
      RESULTS: The overall surgical results were comparable, but more medical
      complications, a longer operative time, and a longer hospital stay were seen in
      the free muscle group. Moreover, patients reconstructed with a medial adipose
      fascial flap appeared to be more satisfied with the aesthetic result of their
      reconstruction. CONCLUSIONS: Muscle coverage is not mandatory to cover bone in
      the lower leg. The medial adipose-fascial flap can provide a good alternative for
      free flap coverage. This flap seems to have fewer medical complications, requires
      a shorter operative time and hospital stay, and can provide better aesthetic
      results than a free muscle flap.

PMID- 15988266
TI  - Defining vascular supply and territory of thinned perforator flaps: part I.
      Anterolateral thigh perforator flap.
AB  - BACKGROUND: The anterolateral thigh perforator flap is increasingly being used
      for trauma and reconstructive surgical cases. With the thinned flap design,
      greater survivability and a decrease in donor-site morbidity are observed. To
      increase our knowledge of the vascular territories in these flaps, an anatomic
      study was performed to determine pedicle number, location, and diameter;
      accompanying veins; vascular territory; and where surgical incisions can be made
      safely during thinning, as opposed to the "danger zone." METHODS: Thirteen
      anterolateral thigh perforator flaps were harvested from seven adult cadavers.
      The largest perforator arteries were cannulated, and flaps were thinned to a
      thickness of 6 to 8 mm, with a 2.5-cm radius from the perforator retained.
      Vascular territories were quantified before and after thinning by nonradiographic
      and radiographic methods. A series of dyes were injected: red dye for skin
      (photography) followed by Omnipaque for the whole flap (radiography) before
      thinning, and blue dye for skin (photography) and lead oxide for the whole flap
      (radiography) after thinning. Pedicle locations were determined by ratios of
      anatomical landmarks. Danger zone measurements were derived at specific
      thicknesses using lateral radiographs of each flap. RESULTS: In anterolateral
      thigh perforator flaps, the mean perforator artery diameter at the fascia level
      was 1.00 +/- 0.08 mm (range, 0.84 to 1.11 mm) and the mean number of perforator
      arteries was 1.69 +/- 1.03 (+/-SD). Perforator pedicles were located near the
      midpoint of the line between the anterior superior iliac spine and the lateral
      aspect of the patella in the vertical axis. The mean vascular territories were
      256 +/- 52.5 cm2 (photography) and 351 +/- 72.8 cm2 (radiography) in unthinned
      flaps and 211 +/- 65.7 cm2 (photography) and 289 +/- 106.6 cm2 (radiography) in
      thinned flaps. Differences in overall vascular territories after thinning were
      83.3 percent (photography) and 81.8 percent (radiography) compared with unthinned
      flaps. Four respective vascular territory maps were drawn showing surgical
      territories using percentile confidence intervals (98th and 90th) and averages.
      From the skin at thicknesses of 4, 6, and 8 mm, the 98th percentile danger zones
      were 33 to 37 mm (proximal to distal), 30 to 35 mm, and 27 to 31 mm from the
      pedicle in the vertical axis, respectively; in the horizontal axis, they were 30
      to 34 mm (medial to lateral), 28 to 31 mm, and 25 to 29 mm. CONCLUSIONS: These
      data define anterolateral thigh perforator flap pedicle location, number, and
      diameter before harvesting, surgical danger zones during thinning, and vascular
      territories after thinning. The authors' guidelines provide surgeons with
      anatomical vascular territory maps to design and harvest specific flaps for
      optimal results.

PMID- 15988267
TI  - Cranial defect regeneration in a reserved space.
AB  - BACKGROUND: Cranial defects exceeding a certain size do not heal spontaneously
      and require surgical treatment. The prevention of uncontrolled soft-tissue
      ingrowth is crucial in the bony healing of such defects. METHODS: Bone
      regeneration of full-thickness cranial defects was assessed in 16 adult New
      Zealand White rabbits. A single epicranially placed cover was compared with a
      hollow chamber with an additional barrier on the dural side. After 8 weeks, bone
      regeneration in the defects was assessed radiologically, histologically, and by
      fluorescence microscopy. RESULTS: The hollow chamber design resulted in almost
      complete cranial defect healing. In contrast, five out of 16 defects covered with
      a single epicranial burr-hole cover showed hardly any visible bone. Inside the
      reserved space, there was twice as much bone coverage as compared with burr-hole
      covers only. CONCLUSIONS: Providing a reserved space for bone regeneration
      reduces the statistical spread significantly and thus makes the clinical outcome
      more predictable. Use of a hollow chamber can serve as a useful tool to assess
      the effect of bone-stimulating factors such as growth factors and bone
      substitutes. Hollow resorbable implants may offer a new approach in bone
      regeneration by reducing the need for bone autografting and the associated donor
      site morbidity.

PMID- 15988268
TI  - Circulating level of vascular endothelial growth factor in differentiating
      hemangioma from vascular malformation patients.
AB  - BACKGROUND: The majority of vascular anomalies can be diagnosed accurately based
      on natural history and physical examination; however, there is no convenient,
      noninvasive, and objective method to (1) differentiate hemangioma from vascular
      malformation; (2) determine whether a hemangioma is in the proliferating or
      involuting phase; (3) tell whether or not corticosteroids or interferon alfa-2a
      is effective for hemangioma; or (4) follow up hemangioma. Although the
      differences in endothelial cell, protein, and mRNA expression levels of some
      positive and negative angiogenic factors in the lesions can help to solve these
      problems, these methods (pathological section, immunohistochemical analysis, and
      in situ hybridization techniques) necessitate that a biopsy be performed, and the
      procedures are complicated. A nonsurgical and convenient method would have
      significant clinical applications. METHODS: Fifty-nine patients with
      proliferating hemangiomas, 38 with involuting hemangiomas, 18 with vascular
      malformations, and 12 negative control subjects were examined for serum levels of
      vascular endothelial growth factor using enzyme-linked immunosorbent assays.
      RESULTS: The serum level of vascular endothelial growth factor in proliferating
      hemangiomas was significantly higher than that in involuting hemangiomas,
      vascular malformations, and negative controls, while differences among involuting
      hemangiomas, vascular malformations, and negative controls were not statistically
      significant. In addition, after systemic steroid therapy, the serum level of
      vascular endothelial growth factor was significantly reduced compared with
      pretreatment levels in six patients with proliferating hemangiomas. CONCLUSIONS:
      The serum level of vascular endothelial growth factor may be useful in
      differentiating hemangioma from vascular malformations, staging hemangiomas,
      judging the efficacy of steroid therapy, and evaluating follow-up criteria for
      hemangiomas. The results probably shed new light on the pathogenesis of
      hemangiomas.

PMID- 15988269
TI  - The effect of tirofiban on microvascular thrombosis: crush model.
AB  - BACKGROUND: Microvascular anastomotic thrombosis is a significant clinical
      problem, particularly in crush and avulsion injuries. Platelet deposition plays a
      particularly important role in the initiation and propagation of microvascular
      thrombosis, whereas thrombin has little effect in the acute phase of thrombus
      formation. Nevertheless, heparin (a specific thrombin inhibitor) remains the most
      widely used microvascular irrigant. The purpose of this study was to evaluate
      tirofiban HCl (Aggrastat), a glycoprotein IIb/IIIa inhibitor, and its role in
      preventing postoperative thrombosis in a crush anastomosis model. METHODS: A
      crush injury model using the rat femoral artery was used. End-to-end
      microvascular repairs were performed. One milliliter of irrigant was used within
      the vessel lumen before placement of the last suture. The irrigant used was
      randomized into one of four groups: lactated Ringer's as a control, tirofiban (50
      microg/ml), heparin (100 U/ml), and a combination of heparin (100 U/ml) and
      tirofiban (50 microg/ml). The vessels were reexamined 24 hours postoperatively
      and patency was assessed. A total of 62 vessels were used for the study. RESULTS:
      The patency rate was two of 20 (10 percent) for the control group, 13 of 22 (59
      percent) for the tirofiban group, one of 10 (20 percent) for the heparin group,
      and eight of 10 (80 percent) for the heparin plus tirofiban group. This study
      demonstrates a statistically significant improvement in patency with tirofiban
      irrigation in a crush anastomosis rat model when compared with saline or heparin
      alone. CONCLUSIONS: Clinically, tirofiban may have utility as a potent
      anticoagulant and is potentially useful in microvascular injuries that have a
      significant crush/avulsion component.

PMID- 15988270
TI  - 5-fluorouracil selectively inhibits collagen synthesis.
AB  - BACKGROUND: Fibroproliferative disorders, such as Dupuytren's contracture of the
      hand, are characterized by excessive production of collagen. 5-Fluorouracil has
      been used to treat fibroproliferative disorders of the eye and skin and is
      thought to inhibit thymidylate synthetase blocking DNA replication. 5
      Fluorouracil has been shown to down-regulate fibroblast proliferation and
      differentiation in vitro. METHODS: This study investigated the dose-dependent
      effect of 5-fluorouracil on fibroblast extracellular matrix production.
      Fibroblasts were derived from tendon and primary Dupuytren's disease of the hand,
      a fibroproliferative disorder of the palmar aponeurosis (n = 4 patients). Total
      collagen synthesis was determined by means of the incorporation of radiolabeled
      proline. Fibroblast secretion of the profibrotic factor transforming growth
      factor-beta1 (TGF-beta1) was measured by a sandwich enzyme-linked immunosorbent
      assay. Gene expression of collagen types I and III and TGF-beta1 were quantified
      by means of reverse-transcriptase polymerase chain reaction assays. RESULTS: The
      authors found that 5-fluorouracil caused a dose-dependent, selective, and
      specific decrease in collagen production by Dupuytren's fibroblasts compared with
      noncollagenous protein synthesis. By contrast, procollagen types I and III mRNA
      were unaffected by 5-fluorouracil treatment. These changes did not appear to be
      mediated by alterations in the endogenous secretion of TGF-beta1 or its autocrine
      effect on collagen metabolism. CONCLUSIONS: The clinical implication is that 5
      fluorouracil could possibly reduce extracellular matrix production and therefore
      reduce recurrence of Dupuytren's disease of the hand.

PMID- 15988272
TI  - Strain-dependent control of transforming growth factor-beta function in
      osteoblasts in an in vitro model: biochemical events associated with distraction
      osteogenesis.
AB  - BACKGROUND: Distraction osteogenesis is an important clinical method for
      increasing bone mass, but its effects on bone-forming cells are not well
      understood. In this study, the authors asked how the mechanical forces that occur
      during this procedure alter specific osteoblast activities such as matrix
      synthesis, the rate of cell replication, and enzyme activities. The authors
      further asked whether these changes relate to differences in the biochemical
      response of osteoblasts to transforming growth factor-beta (TGF-beta), a potent
      regulator of bone formation. METHODS: Osteoblasts were plated on flexible,
      collagen-coated membranes. One group was unstrained, a second group experienced a
      single maximum strain load once every 6 hours to simulate intermittent force
      associated with a distraction protocol of four screw turns per day, and a third
      group was strained continuously for 24 hours. In the third group, some cell
      cultures were allowed to recover from strain before analysis. Subsequently, each
      group was treated with vehicle or TGF-beta at 12 pM (0.3 ng/ml) or 120 pM (3
      ng/ml). Data were collected from a minimum of 15 replicate cell culture wells
      obtained from at least three separate primary culture preparations. Results were
      assessed with statistical software. Differences were considered significant with
      values of p < 0.05. RESULTS: Both strain protocols increased basal osteoblast DNA
      synthesis but suppressed the relative stimulatory effect of TGF-beta on this
      event. However, neither intermittent nor continuous strain significantly altered
      collagen or noncollagen protein synthesis or the relative effect of TGF-beta on
      these processes in osteoblasts. Basal alkaline phosphatase activity, an
      intermediate marker of osteoblast differentiation and an early marker of matrix
      mineralization, decreased significantly in response to continuous strain or to
      TGF-beta treatment, and even more so in response to both conditions. In addition,
      TGF-beta binding to the type III TGF-beta receptor was increased in proportion to
      strain intensity. CONCLUSIONS: This study shows that cyclic strain can alter
      osteoblast activity in multiple ways and predicts that TGF-beta has different
      effects during the distraction process on osteoblasts and therefore on their
      ability to effect bone formation. They further indicate that mechanical load
      permits early aspects of osteoblast activation but delays in part later
      biochemical parameters associated with mineralization to allow new bone growth
      before consolidation.

PMID- 15988273
TI  - A virtual reality model of eustachian tube dilation and clinical implications for
      cleft palate repair.

PMID- 15988274
TI  - Reduction mammaplasty with resection of a trapezoid base prism and adduction of
      the arms.

PMID- 15988275
TI  - A "sandwich toe" flap: a new strategy for reconstruction of the distal phalanx of
      the finger.

PMID- 15988276
TI  - Laser resurfacing of smallpox scars.
AB  - BACKGROUND: At the beginning of the twentieth century, smallpox affected every
      continent and country in the world, but over the first half of the twentieth
      century this disease was eliminated in most countries, including Korea, thanks to
      the World Health Organization's eradication program. Most survivors of smallpox
      have facial scars with a distinct cobblestone appearance. Though most smallpox
      scar patients want smooth skin, it is difficult to achieve good results with
      dermabrasion or chemical peeling. Recently, with advances in laser technology,
      laser resurfacing has become more effective and safer than conventional methods
      because of its depth control precision. METHODS: Between September of 1996 and
      August of 2001, 76 patients with significant smallpox scars were treated with a
      high-powered carbon dioxide laser at Korea University's Anam Medical Center.
      Different resurfacing methods, such as even-depth resurfacing, the shoulder
      technique, and the laser punch-out method, were applied according to the depth
      and pattern of the scars. RESULTS: The authors found that 54 patients (71
      percent) had excellent or good results. The sharply demarcated margins of the
      smallpox scars faded out, and the depth and width of the depressed scars improved
      in most patients. Only seven patients sustained hypertrophic scarring after laser
      resurfacing, but this was resolved by intradermal triamcinolone injections.
      Prolonged erythema occurred in six patients (7.9 percent) and hyperpigmentation
      occurred in 15 (19.7 percent), but the erythema disappeared spontaneously and the
      hyperpigmentation could be readily managed with postoperative skin care.
      CONCLUSION: Laser resurfacing was found to be a useful treatment method for
      smallpox scarring.

PMID- 15988278
TI  - The boxy nasal tip, the ball tip, and alar cartilage malposition: variations on a
      theme--a study in 200 consecutive primary and secondary rhinoplasty patients.
AB  - BACKGROUND: Although "boxy" and "ball" nasal tips have received considerable
      attention in the rhinoplasty literature, their association with cephalic rotation
      of the alar cartilage lateral crura ("malposition") has not been emphasized. The
      thesis of this article is that most boxy and ball tips are not unique entities
      but rather constitute anatomical variants of alar cartilage malposition. METHODS:
      Data were generated from a review of 100 consecutive primary and 100 consecutive
      secondary rhinoplasty patients on whom the author had operated before February of
      1999. RESULTS: The majority of the patients (68 percent of primary rhinoplasty
      patients and 87 percent of secondary patients) studied had alar cartilage
      malposition (axes toward the medial rather than the lateral canthi) (p < 0.001).
      Orthotopic lateral crura were significantly more common than malpositioned
      lateral crura among primary patients (p < 0.001); conversely, the frequency of
      malpositioned crura was significantly higher in secondary patients than in
      primary patients (p < 0.001). Most of the primary and secondary patients with
      malposition (74 percent and 72 percent, respectively) had boxy or ball tips.
      Among patients with alar cartilage malposition, ball tips were most common (31
      percent of primary patients and 36 percent of secondary patients); boxy tips were
      second-most common (19 percent of primary patients and 27 percent of secondary
      patients); the remaining patients had lateral crura that were considered to be
      "flat" (18 percent and 24 percent, respectively). The most common configuration
      among primary patients was the malpositioned boxy or ball tip with inadequate
      projection (54 percent). All primary and secondary rhinoplasty patients with alar
      cartilage malposition, regardless of tip lobular configuration, had incompetence
      at their external nasal valves; valvular reconstruction at least doubled the
      geometric mean nasal airflow in most patients. In primary patients, treatment for
      each variant was identical: lateral crural resection, crushing, and replacement
      along the alar rim. Some secondary patients also required composite grafts.
      CONCLUSIONS: The morphological and functional results of this study indicate that
      the surgeon seeing a patient with a boxy or ball tip can predict that the patient
      has seven times the likelihood of having malpositioned, rather than orthotopic,
      lateral crura. The importance of most boxy and ball tips is therefore not only
      the lobular deformity itself but also the functional deficit associated with it.

PMID- 15988279
TI  - Evaluation of the effects of tip-binding sutures and cartilaginous grafts on tip
      projection and rotation.
AB  - BACKGROUND: Numerous approaches and techniques have been described to achieve a
      desired result in tip surgery, but there are few studies that define or analyze
      the changes that occur after surgery. Therefore, the authors planned a study to
      document changes in nasal tip projection, crural and lobular lengths of the
      columella, columellar length, and proportional relationships of tip projection
      and columella with dorsal length. METHODS: Analysis was based on data collected
      from preoperative and 1-year postoperative lateral views of 18 patients who were
      randomly chosen. The tip-binding suture group included nine patients and the
      cartilaginous graft group included nine patients. The measurements were obtained
      using the parameters regarding tip projection and rotation on standardized
      photographs. The values were statistically analyzed with paired and unpaired t
      tests. RESULTS: The changes in all parameters except crural length were
      statistically significant in the tip-binding suture group. In contrast, the
      statistical analysis of the cartilaginous graft group revealed prominent
      dimensional changes in tip projection and especially in crural and lobular
      segments. CONCLUSIONS: The authors believe that cartilaginous grafts should be
      considered if the dimensional changes have priority in the preoperative plan. The
      columellar strut graft provides satisfactory structural tip support and
      dimensional changes in crural length. Shield grafting causes augmentation in the
      lobular segment. If minor dimensional changes with more rotational alterations
      are planned, tip suture techniques should be preferred.

PMID- 15988280
TI  - Anchor-line abdominoplasty: a comprehensive approach to abdominal wall
      reconstruction and body contouring.
AB  - BACKGROUND: Classic abdominoplasty leads to disappointing aesthetic results in
      patients with preexisting supraumbilical scars. Various techniques involving
      vertical and horizontal incisions have been described. The authors point out the
      validity of the "anchor-line" approach. METHODS: In a retrospective study, the
      authors reviewed the charts of 42 patients who underwent an anchor-line
      abdominoplasty between March of 1997 and March of 2003 at the Campus Bio-Medico
      University in Rome. The vascular anatomy of the abdominal wall was carefully
      reviewed, and they reported Huger's classification into three zones (zones I, II,
      and III). The third zone, which corresponds to the lateral areas of the abdomen,
      provides the vascular supply to the undermined abdominal wall flaps. Whenever
      this lateral vascularization is spared, there is no risk of skin necrosis. The
      anchor-line abdominoplasty implies the en bloc resection of a lower horizontal
      ellipsis plus an upper vertical triangle of abdominal skin and subcutaneous fat.
      The vertical triangle entails the supraumbilical scars. Plication of the rectus
      muscle sheath is always carried out. RESULTS: Follow-up ranged from 1 to 5 years.
      The following complications were seen: seroma (n = 3), anemia (n = 2), infection
      (n = 1), and minor skin necrosis (n = 1). CONCLUSION: The anchor-line technique,
      because of its easy execution, is a valid procedure in candidates for an
      abdominoplasty with supraumbilical median or paramedian scars.

PMID- 15988281
TI  - Calf augmentation and restoration.
AB  - BACKGROUND: Calf augmentation is indicated for cosmetic reasons or to reconstruct
      a shrunken lower leg that is the result of injury, illness, or congenital
      disability. Calf implants are made of solid semisoft silicone, which can be
      customized by carving, or of a thick shell of solid silicone containing cohesive
      silicone. METHODS: During the years 1991 through 2004, 18 patients (13 women and
      five men) underwent 20 calf augmentations at the Lidingo Clinic in Stockholm.
      Indication for operation was aesthetic in 10 patients. Four patients were body
      builders. Another four underwent unilateral crural restoration because of the
      deformity caused by an illness. Both cigar-shaped and anatomically formed
      silicone implants filled with cohesive gel were used. Several technical
      improvements were introduced; among them, a new instrument for insertion of the
      implants. The long-acting anesthetic ropivacaine was used to flush the dissected
      cavity and for intermittent regional analgesia during the first postoperative
      day. One or two implants were placed in the space between the investing crural
      fascia and gastrocnemius muscle, depending on the aesthetic demand. In five
      patients, an augmentation procedure was combined with circumferential liposuction
      of the lower legs. RESULTS: All patients obtained good aesthetic improvement and
      were satisfied with the outcome. No serious complications were encountered in
      this series. Liposuction contributed to better cosmesis and symmetry in some
      aesthetic patients and was particularly important in the reconstructive cases.
      Ropivacaine flush almost eliminated the postoperative pain and discomfort.
      Several clinical examples of calf augmentation attributable for aesthetic and/or
      medical reasons are presented. CONCLUSION: Calf augmentation or reconstruction
      with silicone implants is a safe, efficient, and satisfying aesthetic procedure.

PMID- 15988283
TI  - Circumauricular incision (water-drop shape) for mid- to lower face lift.
AB  - The conventional method of mid- to lower face rhytidectomy that involves removing
      a strip of occipital scalp always creates a conspicuous transverse scar crossing
      the postauricular skin, which may leave a stair-step deformity at the occipital
      hairline. The author has designed a new face lift method using a circumauricular
      incision, shaped like a water droplet, that curves around the auricle. In this
      new method, the upper part of the "O" shape is modified to the tip of a water
      droplet. The dissection of the cheek and neck is performed as in the conventional
      method with light-retractor assistance. The temporal region above the deep
      temporal fascia is managed under endoscopic control. This dissection can extend
      to the forehead region lateral to the supraoptic nerve and around the lateral
      orbital rim to release the arcus marginalis. A mesentery of superficial temporal
      fascia is created cephalic to the zygomatic arch. The postauricular dissection is
      performed beneath the galea in the upper part and beneath the occipital scalp and
      neck skin in the lower area. The lifting vector is upward and backward for the
      anterior skin flap and upward for the posterior skin flap. The excess skin is
      trimmed around the ear. The wound at the upper pole of the incision is closed in
      a V-to-Y advancement fashion. The dog-ear is left above the normal hairline, and
      there is little or no hairy scalp to be removed. The skin pleating in the
      postauricular region will settle down spontaneously after several months. The dog
      ear in the scalp will become smaller and flat as well. The scar around the ear is
      quite inconspicuous and well covered under the upper pole of the auricle. From
      the author's experience, the new "water drop" circumauricular incision is a good
      alternative for the mid- to lower face lift. It can also be used in conjunction
      with endoforehead lift for full-face rejuvenation.

PMID- 15988284
TI  - Effects of mild hypothermia on blood coagulation in patients undergoing elective
      plastic surgery.
AB  - BACKGROUND: The aim of this prospective, controlled study was to evaluate the
      effects on coagulation function of active patient warming during elective plastic
      surgery. METHODS: Seventy-six patients undergoing elective plastic surgery
      (additive and reductive mastoplasty, rhinoplasty, and liposuction) were either
      covered with standard sterile drapes (control group, n = 38) or actively warmed
      during surgery with countercurrent fluid warming and forced-air skin warming
      (treatment group, n = 38). Complete evaluation of the coagulation activity was
      performed 1 hour before general anesthesia was induced and then at the end of
      surgery. RESULTS: Although no differences in preoperative core temperature were
      observed (36.0 +/- 0.5 degrees C in the control group and 36.1 +/- 0.4 degrees C
      in the treatment group; p = 0.12), core temperature was lower at the end of
      surgery in the control group (34 +/- 1.0 degrees C) than in the treatment group
      (36 +/- 0.6 degrees C) (p = 0.0005). No differences in prothrombin time and
      fibrinogen plasma concentrations were observed between the two groups. At the end
      of surgery, control group patients showed significantly larger activated partial
      thromboplastin times (36.8 +/- 3.5 seconds) and bleeding times (8.1 +/- 1.6
      minutes) as compared with patients maintained normothermic during surgery (34.0
      +/- 2.9 seconds and 4.3 +/- 1.1 minutes; p = 0.0005 and p = 0.0005,
      respectively). CONCLUSION: Actively maintaining intraoperative normothermia
      allows patients to maintain normal coagulation function during elective plastic
      surgery lasting longer than 2 hours, potentially reducing the occurrence of
      bleeding-related complications after plastic surgery.

PMID- 15988286
TI  - Aprotinin: role in minimizing perioperative blood loss.

PMID- 15988292
TI  - Management of acute migraine headache with lidocaine.

PMID- 15988293
TI  - Coapt Systems Endotine technology for brow lift.

PMID- 15988294
TI  - The keloid fillet flap.

PMID- 15988295
TI  - Total ear reconstruction using the omental free flap.

PMID- 15988296
TI  - Estimation of breast burn size.

PMID- 15988297
TI  - Estimation of breast burn size.

PMID- 15988298
TI  - Composite syringe dressing after nipple-areola reconstruction.

PMID- 15988299
TI  - The outcome of abdomimoplasty performed under conscious sedation.

PMID- 15988300
TI  - See-and-treat plastic surgery: experience at the University Hospital of North
      Durham.

PMID- 15988301
TI  - Is there any relationship between vascular lesions and blood group?

PMID- 15988302
TI  - A simple modification of the cubital flap to avoid skin grafting of the secondary
      defect.

PMID- 15988303
TI  - Policy for the handling of amputation parts in accident and emergency
      departments.

PMID- 15988304
TI  - Our early experience in the use of tissue glue to reduce the incidence of seroma
      formation from the latissimus dorsi flap donor site.

PMID- 15988305
TI  - Basal cell carcinoma arising in a laparoscopic port site scar at the umbilicus.

PMID- 15988306
TI  - The use of sandpaper as a precision tool for dermabrasion in burn surgery.

PMID- 15988307
TI  - Salvage of an ischemic toe with piracetam.

PMID- 15988308
TI  - Ox tongue: an alternative model for surgical training.

PMID- 15988309
TI  - A no. 2 Prolene suture as a tissue expander.

PMID- 15988310
TI  - Simplest and most convenient method of closing full-thickness skin defects.

PMID- 15988311
TI  - The looped square knot revisited.

PMID- 15988312
TI  - Silicone gel registry requirement.

PMID- 15988314
TI  - Neurobiology of the stress response: contribution of the sympathetic nervous
      system to the neuroimmune axis in traumatic injury.
AB  - Acute injury produces an immediate activation of neuroendocrine mechanisms aimed
      at restoring hemodynamic and metabolic counter-regulatory responses. These
      counter-regulatory responses are mediated by the systemic and tissue-localized
      release of neuroendocrine-signaling molecules known to affect immune function.
      This has led to the recognition of the importance of neuroendocrine-immune
      modulation during acute injury as well as throughout the recovery period. The
      period immediately after acute injury is characterized by upregulation of
      proinflammatory cytokine expression leading to a later period of generalized
      immunosuppression. The course and progression of the host recovery from traumatic
      injury and the integrity of its response to a secondary challenge is directly
      related to the effective control of the immediate proinflammatory responses to
      the initial insult. Among the neuroendocrine mechanisms involved in restoring
      homeostasis, the sympathetic nervous system plays a central role in mediating
      acute counter-regulatory stress responses to injury. In addition to its
      recognized cardiovascular, hemodynamic, and metabolic effects, the
      neurotransmitters released by the sympathetic nervous system have been shown to
      affect immune function through specific adrenergic receptor-mediated pathways. In
      turn, cells of the immune system and their products have been shown to influence
      peripheral and central neurotransmission, leading to the conceptualization of a
      bidirectional neuroimmune communication system. The reflex activation of this
      bidirectional neuroimmune pathway in response to injury, integrated with the
      parasympathetic nervous system, and opioid and glucocorticoid pathways
      responsible for orchestrating the counterregulatory stress response, results in
      dynamic regulation of host defense mechanisms vital for immune competence and
      tissue repair. This review provides the biological framework for the integration
      of our understanding of the neuroendocrine mechanisms involved in mediating the
      stress response and their role in modulating immune function during and after
      traumatic injury.

PMID- 15988315
TI  - Genome-wide monocytic mRNA expression in polytrauma patients for identification
      of clinical outcome.
AB  - Immune activation in multiple trauma is closely linked to the development of
      multiple organ dysfunction and failure, and consequently, has a profound
      influence on patient outcome. Although peripheral blood monocytes play a critical
      role in this immune response, the biological significance of changes in genome
      wide expression immediately after traumatic injury have not been explored
      previously. Thirteen patients presenting with multiple blunt trauma were studied.
      Peripheral blood monocytes were obtained within 90 min and at 6, 12, 24, 48, and
      72 h after trauma. Apparent genome-wide expression was determined with Affymetrix
      U133A microarrays. Supervised analysis identified 698 probe sets that were
      differentially expressed in the 13 trauma subjects (P < 0.001) over the 72-h
      study period. An additional 763 probe sets were differentially expressed in
      patients who died (n = 3) compared with those who survived (n = 10). The ability
      of these probe sets to function as a classifier of survival was significantly
      demonstrated with six prediction models. Using pathway analysis, a network of
      proinflammatory genes and intracellular signaling pathways leading to c-JUN
      activation were consistently overexpressed in patients who died. Genome-wide mRNA
      expression patterns in circulating peripheral blood monocytes from multiple
      injured patients can discriminate clinical outcome. The pattern of gene
      expression in patients who died suggests that in these individuals, there is a
      reprioritization of gene expression consistent with an early activation of
      selected genes involved in the initiation and propagation of a proinflammatory
      response.

PMID- 15988316
TI  - Cytosolic ubiquitin and ubiquitylation rates in human peripheral blood
      mononuclear cells during sepsis.
AB  - The ubiquitin system plays a crucial role in the immune system, and
      ubiquitylation is regarded as one of the most common posttranslational
      modifications of proteins. However, its regulation in human peripheral blood
      mononuclear cells during sepsis is unknown. Thus, we investigated cytosolic
      levels of free and conjugated ubiquitin and the total ubiquitylation rate in cell
      free extracts from healthy donors (n = 10) and patients (n = 10) with sepsis.
      During sepsis, the total ubiquitin concentration was significantly reduced (P <
      0.001), which was caused by a significant decrease in conjugated ubiquitin (7.4
      +/- 1.9 ng vs. 11.75 +/- 1.4 ng conjugated ubiquitin/mug protein, P < 0.001),
      whereas free ubiquitin was unchanged. The proportion between free and conjugated
      ubiquitin showed a linear relationship in physiologic conditions (r, 0.76, P =
      0.001) but not in sepsis (r, 0.27, P = 0.12). These changes were accompanied by a
      decreased total ubiquitin protein ligase activity (1.7 +/- 1.1 pkat/mg vs. 5.7 +/
      2.9 pkat/mg, P = 0.002). The tight regulation of the cytosolic ubiquitin pool
      appears to be significantly altered during sepsis. In addition to alterations in
      ubiquitin turnover, these findings suggest that reduced ubiquitylation rates also
      contribute to the decrease in endogenous conjugated ubiquitin. This indicates
      that a major pathway of posttranslational protein modification in all eukaryotes
      is profoundly altered in peripheral blood mononuclear cells from critically ill
      sepsis patients. This may contribute to the well-known impairment of host defense
      mechanisms in sepsis.

PMID- 15988317
TI  - Interleukin 12 and interferon-gamma synthetic deficiency is associated with
      dendritic cell cytopenia after cardiac surgery.
AB  - Traumatic or inflammatory injury associates with deactivation of monocytes and
      impaired synthesis of proinflammatory cytokines. We conducted a prospective,
      observational study to test whether cardiac surgery additionally impaired
      dendritic and natural killer (NK) cell functions responsible for innate immune
      production of interleukin (IL)-12-dependent interferon (IFN)-gamma in response to
      bacteria or toll-like receptor agonists. Blood samples were taken just before
      induction of anesthesia and 24 h postoperatively. LPS- and fixed Staphylococcus
      aureus-inducible IFNgamma synthesis in whole blood culture after surgery was
      reduced to 5% of preoperative values (P < 0.001). Production of IL-12 p70, a
      critical inducer of IFNgamma in the innate immune response, was reduced to 30% of
      that produced by preoperative samples (P = 0.013). Circulating CD11c, DR myeloid
      dendritic cells (DC) that are known sources of IL-12 p70 in normal blood,
      declined to approximately 25% of presurgical numbers (P = 0.004). Experimental
      depletion of CD11c, but not CD14, cells from normal peripheral blood mononuclear
      cell (PBMC) similarly disabled Staphylococcus aureus Cowan 1 (SAC)-induced
      production of IL-12 p70 and IFNgamma. Consistent with SAC-induced IFNgamma
      expression in CD56 NK and NK-T cells, CD56 depletion ablated IFNgamma production
      in normal whole blood. However, repletion of IL-12 p70, IL-18, IL-15, and IL-23
      in postoperative blood failed to restore presurgical levels of IFNgamma synthesis
      (P < 0.05). We conclude that DC cytopenia after major surgery is sufficient to
      explain postoperative IL-12 p70 and IFNgamma synthetic deficiency. In addition,
      postoperative blood became hyporesponsive to IFNgamma-inducing cytokines as a
      further contribution to IFNgamma insufficiency. The novel finding of DC cytopenia
      after major surgery may portend a lack of other immunologic functions provided by
      this potent accessory cell population.

PMID- 15988318
TI  - Association between nucleated red blood cells in blood and the levels of
      erythropoietin, interleukin 3, interleukin 6, and interleukin 12p70.
AB  - The appearance of nucleated red blood cells (NRBC) in the circulation is
      associated with a variety of severe diseases, and indicates a relatively poor
      prognosis. Whether a malfunction of the bone marrow leads to this phenomenon is
      as unknown as the possible role that cytokines could play in this process. We
      analyzed erythropoietin, interleukin (IL)-3, IL-6, and IL-12p70 in the blood of
      301 patients with circulating NRBCs. Two hundred fifty NRBC-negative patients
      served as controls. Multiple logistic regression revealed a significant
      association between the appearance of NRBCs in the blood and erythropoietin (odds
      ratio, 1.017; 95% confidence limits, 1.007-1.027; P < 0.001), IL-3 (odds ratio,
      1.293; 95% confidence limits, 1.180-1.417; P < 0.001), IL-6 (odds ratio, 1.138;
      95% confidence limits, 1.016-1.275; P < 0.05), and age (odds ratio, 1.019; 95%
      confidence limits, 1.009-1.030; P < 0.001), respectively. Gender and IL-12p70
      were not significantly associated with the appearance of NRBC in the blood. To
      estimate the RBC production in the bone marrow, the increase in the reticulocyte
      concentration in blood was measured. The reticulocyte concentration in NRBC
      positive patients was 69 +/- 2/nL, which was significantly higher than in NRBC
      negative patients (60 +/- 2/nL; P < 0.01). Taken together, NRBC could be a marker
      that sums up hypoxic and inflammatory injuries. Thus, generally, the appearance
      of NRBC in blood is a valid parameter to identify patients at high mortal risk.
      Moreover, the increased number of reticulocytes in the blood of NRBC-positive
      patients may indicate that the appearance of NRBC is not associated with
      disturbed bone marrow function as far as the erythropoiesis is concerned.

PMID- 15988319
TI  - Harmful and protective roles of neutrophils in sepsis.
AB  - The current studies demonstrate protective and harmful effects of neutrophils
      (PMN) during experimental sepsis after cecal ligation and puncture (CLP). It is
      known that CLP induces signaling defects in blood PMN. When PMN were depleted 12
      h after CLP, there were dramatic reductions in levels of bacteremia, evidence for
      reduced liver and renal dysfunction, sharp reductions in serum levels of
      cytokines (IL-1beta, IL-6, IL-10, TNF-alpha, and IL-2), and improved survival. In
      contrast, PMN depletion before CLP resulted in substantial increases in
      bacteremia and no evidence for attenuation of liver and renal failure
      dysfunction. These data suggest that at the onset of sepsis, PMN are important in
      regulating the levels of bacteremia, whereas after the onset of sepsis, as they
      lose innate immune functions, their presence is associated with higher levels of
      bacteremia and intensified organ dysfunction.

PMID- 15988320
TI  - Rapid alterations in transferrin sialylation during sepsis.
AB  - The inflammatory process is associated with alterations in iron metabolism.
      Transferrin, an acute-phase N-glycosylated glycoprotein, plays an important role
      in iron transport. Human serum transferrin contains two biantennary glycans, each
      consisting of 0 to 4 molecules of sialic acid (SA); its SA content is
      heterogeneous with high concentration of tetrasialotransferrin (4SA) and low
      amounts of disialo-, trisialo-, penta-, and hexasialotransferrin. The hepatic
      uptake of iron is greater for desialylated transferrin isoforms
      (disialotransferrin) than for the other forms. We hypothesized that serum levels
      of carbohydrate-deficient transferrin (CDT, disialotransferrin) may increase
      rapidly in septic patients. Blood samples were obtained from critically ill
      patients with (n = 15) and without (n = 14) documented sepsis and compared with
      healthy volunteers. The different forms of transferrin were studied by capillary
      zone electrophoresis; SA concentrations were measured by enzymatic colorimetric
      assay. There was a significant increase in the proportion of CDT in septic
      compared with nonseptic patients and volunteers (18.3% [1.3-30.5] vs. 0.7% [0.5
      0.9]; P < 0.01 and 0.9% [0.5-1.1]; P < 0.05). Conversely, tri- and
      tetrasialotransferrin levels were lower in septic patients. Total and free SA
      concentrations were significantly higher in septic patients than in healthy
      volunteers. In a sheep model of septic shock secondary to peritonitis, serum free
      SA was already increased after 15 h. Sepsis is associated with decreased SA
      content on circulating transferrin and with an increase in blood free SA
      concentrations. In view of these rapid modifications and the long half-life of
      transferrin, the most likely explanation is degradation of transferrin by
      neuraminidase. Further studies including measurement of blood neuraminidase
      concentration and activity are needed to understand the process and exact role of
      SA decrease in septic patients.

PMID- 15988322
TI  - 15-Deoxy-delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), a peroxisome proliferator
      activated receptor gamma ligand, reduces tissue leukosequestration and mortality
      in endotoxic shock.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear
      receptor that requires ligand activation for transcription. Experimental studies
      have shown that 15-deoxy-Delta-PGJ2 (15d-PGJ2) is a natural PPARgamma ligand
      which has potent anti-inflammatory properties. This study was designed to examine
      the effect and the molecular mechanisms of 15d-PGJ2 on tissue neutrophil
      infiltration and survival in endotoxic shock. Male Swiss albino mice were
      subjected to intraperitoneal injection of Escherichia coli lipopolysaccharide
      (LPS, 25 mg/kg). Three hours after LPS mice received vehicle or 15d-PGJ2 (1
      mg/kg) and continued treatment every 12 hours. Survival was monitored for 72
      hours. In a separate experiment, mice were sacrificed 6 hours after LPS and
      tissue examined. In vehicle-treated mice, LPS injection resulted in a survival
      rate of 9%. Marked lung injury was characterized by hemorrhage, infiltration of
      inflammatory cells and reduction of alveolar space. Elevated levels of
      myeloperoxidase activity in lung and small intestine were indicative of
      infiltration of neutrophils. Increased expression of intercellular adhesion
      molecule-1, vascular cellular adhesion molecule-1 and E-selectin were observed in
      the lung and small intestine. These inflammatory events were associated with
      reduced expression of PPARgamma and with activation of nuclear factor-kappaB (NF
      kappaB) in the lung. Treatment with 15d-PGJ2 improved survival rate to 55%,
      downregulated expression of adhesion molecules and reduced neutrophil
      infiltration in tissues. These beneficial effects were associated with reduced
      activation of NF-kappaB DNA binding, whereas expression and DNA binding of
      PPARgamma and expression of the cytoprotective heat shock protein (HSP) 70 were
      increased in the lung. Our data demonstrate that 15d-PGJ2 ameliorates endotoxic
      shock most likely through repressing the proinflammatory pathway of NF-kappaB and
      enhancement of the cytoprotective heat shock response.

PMID- 15988321
TI  - Rho-associated kinase modulates myocardial inflammatory cytokine responses.
AB  - Rho, a Ser-Thr kinase identified as a member of the RAS GTPase super family, is
      highly expressed in the heart, and has been implicated in the development of
      heart failure. GTPase Rho is located downstream of Gq, and Rho and the associated
      kinase (Rho kinase) regulate myofibril organization, apoptosis, and myofibrillar
      sensitivity to calcium. Myocardial injury and dysfunction occur after major burn
      injury, and this phenomenon has been linked to cardiac myocyte synthesis and the
      secretion of proinflammatory cytokines. Whether Rho-associated kinase modulates
      any aspect of cardiomyocyte synthesis of inflammatory mediators, contributing to
      myocardial dysfunction, has not been studied and was the focus of this study.
      Hearts were collected at several times postburn to determine if an acute injury
      such as thermal trauma altered myocardial Rho kinase expression. In addition,
      cardiomyocytes were isolated (collagenase digestion) from adult control Sprague
      Dawley rats, plated (5 x 10 cells/microtiter well), incubated with medium alone
      or in the presence of burn serum (collected 24 h after burn over 40% total body
      surface area in rats) in a CO2 incubator at 37 degrees C in the presence/absence
      of specific Rho-kinase inhibitors (HA1077, 10 microM or Y27632, 10 microM). After
      18 h, supernatants were collected to measure secreted cytokines (enzyme-linked
      immunoabsorbant assay), cells were loaded with Fura-2AM (2 microg) or sodium
      binding benzofuran isophthalate (2 microg) for 45 min at 37 degrees C, and
      fluorescence was measured with an InCyt IM2 fluorescence imaging system to
      measure myocyte calcium and sodium. In parallel studies, cells were examined to
      determine if burn serum challenge increased Rho kinase in this cell population.
      In vivo burn injury or in vitro burn serum challenge of isolated myocytes
      increased Rho-kinase expression and promoted cardiomyocyte secretion of tumor
      necrosis factor-alpha, interleukin 1beta, and interleukin 6, and increased
      cardiomyocyte calcium and sodium levels compared with values measured when
      myocytes were incubated in medium alone (P < 0.05). Pretreating cardiomyocytes
      with Rho-kinase inhibitor (HA1077 or Y27632) prevented burn serum-related
      upregulation of Rho-kinase and attenuated the associated inflammatory cytokine
      responses, and attenuated myocyte calcium and sodium loading. Our data suggest
      that the Rho-kinase pathway is one potential upstream regulator of cardiac
      inflammatory response to burn injury.

PMID- 15988323
TI  - Early difference in tissue pH and microvascular hemodynamics in hemorrhagic shock
      resuscitation using polyethylene glycol-albumin- and hydroxyethyl starch-based
      plasma expanders.
AB  - The hamster chamber window model was subjected to hemorrhagic shock by the
      withdrawal of 50% of blood volume (BV). BV was restored 1 h after hemorrhage with
      a single volume infusion (resuscitation) of 25% BV with polyethylene glycol (PEG)
      conjugated bovine serum albumin (Alb) and hydroxyethyl starch (HES). Hemorrhage,
      shock, and resuscitation were monitored continuously in terms of mean arterial
      pressure (MAP), microvascular blood flow, capillary perfusion, and tissue pH.
      Blood samples for laboratory parameters were taken at baseline, shock, and
      resuscitation. Intravascular and tissue pO2 were assessed after resuscitation,
      and microvascular oxygen supply and extraction were calculated and corrected for
      pH effect on hemoglobin saturation. Resuscitation with PEG-Alb restored systemic
      and microvascular parameters up to the end of the observation period (90 min).
      HES was identical to PEG-Alb resuscitation during the initial 10 to 15 min, but
      was not sustained subsequently. The trend of recovery in MAP for HES persisted
      beyond the time when both function capillary density and tissue pH decreased,
      thus MAP was not indicative of early microvascular dysfunction. Hemoglobin oxygen
      saturation estimation showed a significant pH dependence. However, oxygen
      dependant parameters corrected for pH varied less than 10% from uncorrected data.
      Early differences found at the microvascular levels suggest that decisions to
      amend end-result of resuscitation may be short and on the order of minutes.
      Furthermore, PEG-Alb appears to provide early and long-term sustained systemic
      and microvascular recovery when used to restitute perfusion and metabolic
      conditions after resuscitation from hemorrhagic shock.

PMID- 15988324
TI  - The acute inflammatory response in diverse shock states.
AB  - A poorly controlled acute inflammatory response can lead to organ dysfunction and
      death. Severe systemic inflammation can be induced and perpetuated by diverse
      insults such as the administration of toxic bacterial products (e.g., endotoxin),
      traumatic injury, and hemorrhage. Here, we probe whether these varied shock
      states can be explained by a universal inflammatory system that is initiated
      through different means and, once initiated, follows a course specified by the
      cellular and molecular mechanisms of the immune and endocrine systems. To examine
      this question, we developed a mathematical model incorporating major elements of
      the acute inflammatory response in C57Bl/6 mice, using input from experimental
      data. We found that a single model with different initiators including the
      autonomic system could describe the response to various insults. This model was
      able to predict a dose range of endotoxin at which mice would die despite having
      been calibrated only in nonlethal inflammatory paradigms. These results show that
      the complex biology of inflammation can be modeled and supports the hypothesis
      that shock states induced by a range of physiologic challenges could arise from a
      universal response that is differently initiated and modulated.

PMID- 15988325
TI  - Lipid peroxidation inhibition by raxofelast improves angiogenesis and wound
      healing in experimental burn wounds.
AB  - We investigated the effects of raxofelast, a lipid peroxidation inhibitor, in an
      experimental model of burn wounds. C57BL/6 male mice of 25-30 g were immersed in
      80 degrees C water for 10 seconds to achieve a partial-thickness scald burn.
      Animals received intraperitoneally either raxofelast (20 mg/kg/day for 14 days in
      100 microL) or its vehicle alone (100 microL/day for 14 days). On day 14, burn
      areas were used for measuring conjugated dienes, reduced glutathione levels,
      histological damage, neoangiogenesis by immunohistochemistry and expression
      (Western blot) of the specific endothelial marker CD31 as well as quantification
      of microvessel density, VEGF wound content, endothelial and inducible nitric
      oxide synthase (eNOS and iNOS) expression and wound nitrite content. Raxofelast
      decreased tissue conjugated dienes (vehicle 6.1 +/- 1.4 DeltaABS/mg protein;
      raxofelast 3.7 +/- 0.8 DeltaABS/mg protein), prevented tissue glutathione
      consumption (vehicle 3.2 +/- 0.9 micromol/g protein; raxofelast 6.7 +/- 1.8
      mumol/g protein), increased epithelial proliferation, extracellular matrix
      maturation, and augmented neoangiogenesis as suggested by the marked increase in
      microvessel density and by the robust expression of the specific endothelial
      marker CD31 (vehicle 9.4 +/- 1.1 integrated intensity; raxofelast 14.8 +/- 1.8
      integrated intensity). Furthermore, raxofelast enhanced VEGF wound content
      (vehicle 1.4 +/- 0.4 pg/mg protein; raxofelast 2.4 +/- 0.6 pg/mg protein), caused
      a marked expression of eNOS (vehicle 16.1 +/- 3 integrated intensity; raxofelast
      26.2 +/- 4 integrated intensity) and iNOS (vehicle 9.1 +/- 1.8 integrated
      intensity; raxofelast 16.2 +/- 3.5 integrated intensity) and increased wound
      nitrite content. Lipid peroxidation inhibition by raxofelast may be an effective
      therapeutic approach to improve clinical outcomes after thermal injury.

PMID- 15988326
TI  - Benefit of slow infusion of hypertonic saline/dextran in swine with uncontrolled
      aortotomy hemorrhage.
AB  - In laboratory models of uncontrolled hemorrhage, immediate resuscitation from
      hemorrhage is associated with high mortality. However, in clinical practice,
      resuscitation is often delayed and the rate of fluid administration is limited.
      We hypothesized that a slow rate of infusion after delayed resuscitation,
      reflecting the clinical environment, might improve survival in the presence of
      uncontrolled hemorrhage. To investigate the rate of administration in the
      presence of delayed resuscitation, we subjected anesthetized swine weighing 35 to
      45 kg to wire suture abdominal aortotomy that resulted in an uncontrolled
      hemorrhage. After a 30-min delay, hemorrhaged swine were infused i.v. with 4
      mL/kg hypertonic saline/Dextran solution (7.5% saline in 6% Dextran 70)
      administered as a bolus over 1 min or as a slow infusion over 12 min (the time
      period to administer a similar volume to a human with a gravity feed i.v. and an
      18-gauge needle) and were then monitored for another 90 min. Survival increased
      to 78% (seven of nine) in the slow infusion group compared with a survival rate
      of 56% (five of nine) in the bolus group and 50% (7/14) in the untreated
      controls. Blood loss was significantly higher in the bolus group (926 +/- 77 mL)
      compared with the slow infusion (714 +/- 83 mL) and control groups (604 +/- 46
      mL). Hypertonic saline/Dextran administered slowly significantly increased
      cardiac output and blood pressure. Taken together, these results are consistent
      with the hypothesis that resuscitation solutions can be effective for treatment
      of uncontrolled hemorrhage when administered at a slow infusion rate 30 min after
      the insult.

PMID- 15988327
TI  - Myocardial ischemia/reperfusion-induced oxidative renal damage in rats:
      protection by caffeic acid phenethyl ester (CAPE).
AB  - Myocardial ischemia-reperfusion (MI/R) may induce renal damage. A rat model of
      M/IR injury was established. The left coronary artery was clamped for 30 min,
      constituting the ischemic period, and was then released for 120 min, thus
      constituting the reperfusion period. The purpose of this study was to evaluate
      the effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on renal
      dysfunction in rats undergoing MI/R. CAPE (50 mumol/kg) was administered by
      infusion 10 min before ischemia and during occlusion. Hemodynamic changes were
      recorded during the different periods. At the end of the reperfusion period, rats
      were sacrificed, and the kidneys were quickly removed for biochemical
      determination and histopathological analysis. MI/R was accompanied by a
      significant increase in malondialdehyde (MDA) production and decrease in
      glutathione (GSH) content in the rat kidney. Administration of CAPE reduced MDA
      production and prevented depletion of GSH content. These beneficial changes in
      these biochemical parameters were also associated with parallel changes in
      histopathological appearance. These findings imply that MI/R plays a causal role
      in kidney injury through overproduction of oxygen radicals or insufficient
      antioxidant, and CAPE exerts renal-protective effects probably by its radical
      scavenging and antioxidant activities.

PMID- 15988330
TI  - [Emergency room deaths.]
AB  - 3-MONTH RETROSPECTIVE ANALYSIS: OBJECTIVES: Determine the characteristics of
      patients who died in the emergency unit and assess the number for whom care was
      limited or withdrawn. METHODS: A 3-month single-center retrospective study of all
      the patients who died in the emergency room. Bivariate analysis was used to
      compare the clinical characteristics of patients who died despite maximum care
      (MC) with those for whom care was limited (LC). RESULTS: 84 patients died during
      the study period: 48 men and 36 women (mean age: 73 +/- 18 years). Half had
      normal mobility (43 patients, 50%), and 35 (40%) lived at home. Nearly all (72
      patients, 72%) had a severe chronic disease. In descending order, death was
      ascribed to neurological (n=22, 24%), cardiac (n=14, 15%), septic (n=13, 14%) and
      respiratory (n=9, 10%) causes. The decision was made to limit or stop active care
      for 73 patients (84%) and recorded in 48 case files (55%). The principal
      differences between patients receiving MC and LC were respectively C and D Knaus
      classification and their age. CONCLUSION: Death is frequent in emergency units
      and often strikes elderly patients with impaired mobility and severe chronic
      diseases. The decisions to limit or stop active care are the predominant direct
      cause, but their modalities warrant further exploration in a prospective study.

PMID- 15988331
TI  - Key points.

PMID- 15988332
TI  - [Prevention of cardiovascular risks, in pursuit of excellence.]

PMID- 15988333
TI  - [Mortality related to the heatwave in 2003 in France: forecasted or over the
      top?].

PMID- 15988334
TI  - [A purposeful research policy, now].

PMID- 15988335
TI  - [Authors' affiliations and addresses in published articles. Lack of care
      penalizes French universities in international rankings].
AB  - OBJECTIVE: To assess, through the example of the universite Claude Bernard Lyon
      1, whether the poor international visibility of French universities may be due in
      part to a lack of care by researchers in listing their affiliations and address
      on their scientific publications. METHOD: Querying the heading "address" of
      Medline, Embase.com and Pascal Biomed for 2003 in searches for publications from
      Universite Claude Bernard Lyon 1. RESULTS: In 300 bibliographic entries studied,
      we found 44 different forms of the university's name. Only 15% of the addresses
      were correct, and 44% did not mention the author's affiliation with the
      university. DISCUSSION: Authors' lack of care in listing their affiliations and
      address and the absence of a standardized official name for the university may
      explain the poor visibility of French universities. Recommendations about this
      topic might help to promote the reputation and work of French researchers
      internationally.

PMID- 15988336
TI  - [A descriptive national survey of 166 Alzheimer health networks].
AB  - OBJECTIVE: Assess and describe the organization, operation, and aims of Alzheimer
      health networks in France. METHODS: Questionnaire sent by post or handed to
      physicians in France identified as involved in management of Alzheimer patients
      by Novartis Pharma sales representatives. RESULTS: 166 networks managing
      Alzheimer's disease (2/3 primarily gerontological and 1/3 specializing
      specifically in Alzheimer's). In 61.9% of the cases, the physician supervising
      the network was a hospital staff physician, often a geriatrician (48%). The other
      member physicians were essentially general practitioners. Several paramedics and
      social workers also participated. Most networks were organized as not-for-profit
      organizations. Financial support most often came from the relevant ministries and
      the health insurance funds. The number of active cases handled by the networks
      could not be globally assessed. The operating tools for the networks included
      membership charters, management guidelines and protocols, and shared medical
      files, but fewer than 30% of the networks used any one of these. The networks had
      as their primary objectives training and information, patient follow-up and
      gerontological coordination. These aims were consistent with the goals they felt
      that had come closest to attaining, i.e., improving the quality and organization
      of care, sharing information with and training other health professionals, and
      providing information to the public. Barely one third of the networks had
      developed an assessment procedure. Among the obstacles to network operations were
      the participants' lack of availability, the absence of collaboration between
      professionals, and financial problems. CONCLUSION: Despite the disparity in the
      quality and exhaustiveness of the data collected, our survey confirmed the
      diversity and dynamism, but also the lack of formal structure and the
      difficulties confronted by the Alzheimer networks in France.

PMID- 15988337
TI  - [Multisystemic amyloidosis. Clinical study of 39 patients in Lebanon].
AB  - OBJECTIVE: Clinical analysis of multisystem amyloidosis in Lebanon, by
      histological type. METHOD: Retrospective study of 39 cases of multisystem
      amyloidosis diagnosed histologically in a university hospital center between 1991
      and 2002. It analyzed the following clinical data: age, gender, type of
      presentation, time from symptom onset to diagnosis, clinical features,
      concomitant diseases, family history of amyloidosis, biopsy sites, presence of
      urinary or serum monoclonal gammopathy, immunohistochemical type, prognosis and
      treatment. RESULTS: Median age at diagnosis was 56+/-18 years. The overall ratio
      of men to woman was 1.4. AL amyloidosis (amyloid light chain) accounted for 54%
      (21/39) of the cases, AA (amyloid-associated) amyloidosis 36% (14/39), while 10%
      (4/39) were not typed. Among the 21 cases of AL amyloidosis, 12 were idiopathic
      (57%) and 9 (43%) were associated with multiple myeloma; among the 14 cases of AA
      amyloidosis, 7 were associated with familial Mediterranean fever and 5 with
      chronic disorders. Proteinuria was often the first symptom. The initial
      manifestations in AL amyloidosis patients with myeloma were more often related to
      amyloidosis than to myeloma. Renal involvement was seen in 95% (37/39) of all
      cases (95% of AL versus 93% of AA), proteinuria in 87% of cases and renal failure
      in 72%. Cardiac amyloidosis (57% of AL versus 7% of AA; p>0.05), infiltration of
      the tongue (19% of AL versus 0% of AA; p>0.05) and neurological manifestations
      (24% of AL versus 7% of AA; p>0.05) were more frequent in AL amyloidosis. The 7
      patients who died (18%) had AL amyloidosis (5 of them had myeloma). Heart failure
      was the most frequent cause of death related to amyloid. CONCLUSION: Multisystem
      amyloidosis is frequent in Lebanon and familial Mediterranean fever is still
      frequently associated with the secondary type. Accurate diagnosis and
      classification are essential for the prognosis and treatment of the disease. Poor
      prognosis was associated with the AL type, especially when accompanied by
      myeloma, and with cardiac amyloidosis.

PMID- 15988338
TI  - [Severe dehydration and August 2003 heat wave in a cohort of adults with cystic
      fibrosis].
AB  - OBJECTIVE: To study dehydration related to the August 2003 heat wave in France in
      a cohort of adults with cystic fibrosis. Method Retrospective study of the
      telephone calls received from and hospital admissions of all adult cystic
      fibrosis patients (n=245) regularly followed in our specialized clinic. RESULTS:
      Six patients developed extracellular dehydration with functional kidney failure
      concomitant to intracellular dehydration with hypokalemia and hypochloremia.
      Rehydration measures normalized the blood chemistry measures within 48 hours for
      all patients except one, who died of malignant hyperthermia. CONCLUSION: In hot
      weather, it is essential for patients with cystic fibrosis to take measures
      (hydration, salt supplementation) to prevent severe dehydration.

PMID- 15988339
TI  - [Pigmented villonodular synovitis].
AB  - OBJECTIVE: To evaluate clinical, radiological and histological characteristics as
      well as outcome of pigmented villonodular synovitis (PVNS) in 14 patients.
      METHODS: This retrospective study examined data from 14 cases of pathologically
      confirmed PVNS over a 10-year period (1990-1999). RESULTS: All 14 cases (9 women
      and 5 men) of PVNS involved the knee. Mean age at diagnosis was 32.7 years. The
      principal functional signs were mechanical pain and disability. All patients had
      radiographs (normal for 8 patients); 3 had arthrography, which found diffuse cyst
      formations, 2 had MRI, which showed images characteristic of PVNS, and 4 had
      arthroscopy. All patients underwent complete surgical excision, and 4 also had
      osmic acid synoviorthesis. Recurrence occurred in 4 patients, within 10 months on
      average. CONCLUSION: MRI and arthroscopy improve the early management of
      pigmented villonodular synovitis.

PMID- 15988340
TI  - [Autochthonous hepatitis E virus in Southeastern France. 2 cases].
AB  - INTRODUCTION: Hepatitis E virus is endemic in developing countries where it is
      especially lethal among pregnant women. As the circulation of goods and people
      grows between these countries and the industrialized nations, this virus is
      emerging as a cause of imported acute hepatitis in the latter, where authentic
      autochthonous cases also exist. OBSERVATIONS: We report two cases observed in
      Marseille, in men aged 27 and 81 years; no mode of contamination was detected,
      and both outcomes were positive. DISCUSSION: This virus is circulating in non
      endemic areas (as shown by its seroprevalence, which ranges from 0.4 to 2.6%, its
      identification in urban sewage, and the autochthonous cases reported). This
      dissemination, combined with its high mortality rate, even outside pregnancy (up
      to 12%), show the need for systematic consideration of and an early search for
      the often-fleeting presence of the virus and of IgM and IgG type serum antibodies
      in plasma and (when necessary) feces in cases of acute hepatitis, because of
      their often transient nature. Prophylaxis is based on improving water hygiene and
      is thus more difficult in industrialized countries where the level of hygiene is
      already high, especially when no risk factors can be identified in the
      autochthonous cases. Recombinant vaccines are under development.

PMID- 15988341
TI  - [Ossification of the common posterior longitudinal ligament of the spine and
      spinal cord compression in a patient from Senegal].
AB  - INTRODUCTION: Ossification of the posterior longitudinal ligament of the spine is
      a rare cause medullar compression. OBSERVATION: A 50-year-old man from Senegal
      was referred with recent-onset mechanical lumbar pain with proximal motor
      deficiency of the lower limbs and somatosensory disorders. Magnetic resonance
      imaging revealed layered medullar compression, due to anterior cervical and mixed
      anterior and posterior thoracic ossification. Corticosteroid treatment led to
      regression of the pain and neurological disorders within a few days. DISCUSSION:
      This case report of ossification of the posterior longitudinal ligament of the
      spine appears to be an idiopathic form corresponding to the "Japanese disease"
      initially thought to be limited to that population.

PMID- 15988342
TI  - [Rash and nephrotic syndrome: consider syphilis].
AB  - INTRODUCTION: Kidney disease is among the clinical manifestations of secondary
      syphilis, as this case report shows. OBSERVATION: During serologically confirmed
      secondary syphilis, a 63-year-old man developed a nephrotic syndrome diagnosed
      after biopsy as membranous nephropathy. DISCUSSION: Membranous nephropathy is an
      immunological complication of secondary syphilis. Recovery usually follows
      treatment. It is often associated with signs that may erroneously suggest
      connective tissue disease.

PMID- 15988343
TI  - [The mirages of the hospital-enterprise].

PMID- 15988345
TI  - [Diagnosis of psychological and behavioural disorders in Alzheimer's disease].
AB  - Although Alzheimer's disease has long been considered mainly a cognitive
      disorder, behavioral and psychological symptoms are present from its onset and at
      all the stages of the disease in most patients. They must be identified from the
      beginning because they orient the diagnosis. They include affective and emotional
      disorders, delusions and hallucinations, disorders of instinctual behavior and
      behavioral problems. The best tool for assessing them is the Neuropsychiatric
      Inventory (NPI). They are generally related to neurobiological aspects of the
      disease but may, especially when acute, have multiple etiologies: somatic,
      iatrogenic, psychological and environmental. They condition the course of the
      disease. As a source of suffering and reduced quality of the life and as the
      primary cause of distress for the caregivers and hence of hospitalization and
      institutionalization, they increase the costs of care. The challenge today is to
      learn more about them and thus improve their treatment and especially their
      prevention.

PMID- 15988346
TI  - [Treatment of the psychological and behavioural disorders of Alzheimer's
      disease].
AB  - When psychological and behavioral disorders of Alzheimer's disease appear
      suddenly, somatic, iatrogenic and reactive or relational psychological causes
      must be ruled out or treated before concluding that the cause is lesional. Non
      pharmacological interventions should be privileged for the prevention and
      management of behavioral manifestations of mild to moderate intensity:
      psychological support of the patient (short therapies), training the caregiver,
      work on daily habits, reorganization of the home, behavioral measures against
      apathy and especially agitation, rehabilitation strategies, and therapy involving
      music, light, aromas, etc. Pharmacological therapies are only moderately
      effective in these disorders. They must be targeted and follow a sequence of
      prescription that maximizes tolerance and distinguishes treatment of acute and
      chronic states. Anticholinesterase agents may be useful in this domain to prevent
      or ease some symptoms (especially apathy). The efficacy of memantine must be
      confirmed by additional data. Some selective serotonin reuptake inhibitors agents
      may be useful not only in depression but also anxiety, emotional disturbances,
      irritability and compulsiveness. Atypical neuroleptics are better tolerated than
      the classic ones. They are most effective in this context but must be reserved
      for specific indications and limited in time because of the increased risk of
      stroke. Other psychotropics (benzodiazepines, carbamates, antiepileptics) should
      be used cautiously in this context.

PMID- 15988347
TI  - [The handling of anti-cancer drugs in elderly patients].
AB  - The management of elderly patients with cancer is not established. The use of
      antineoplastic agents (particularly of chemotherapy) raises a lot of questions.
      Efficiency and toxicity. Data come from subgroups of clinical trials and from
      selected populations. Chronological age itself does not contra-indicate
      chemotherapy. Pharmacokinetics. Physiologic and functional changes occur with
      aging but there is great inter-patient variability. Oral chemotherapy. Oral
      treatments underline the problem of compliance. Under-treatment. Elderly patients
      are under-represented in clinical trials. Relevant issues have to be defined
      individually and cancer's real place in patient's general situation has to be
      specified. Geriatric assessment. This tool has proved its usefulness in many
      domains for global management of elderly patients. A multidisciplinary team is
      necessary, under geriatrician coordination. The aim is to elaborate an
      individualized medico-social intervention program. Geriatric assessment in
      oncology. Its interest for cancer patients is shown by emerging reports but its
      routine use by oncologists is impossible. Treatment strategies. They are not
      validated. FUTURE: New clinical and pharmacokinetic studies are necessary in
      order to specify the place of the various tools and to enhance the handling of
      such molecules.

PMID- 15988348
TI  - [Systemic mastocytosis].
AB  - Systemic mastocytosis is characterized by abnormal mast cell proliferation in
      different organs. The 2001 consensus classification distinguishes in separate
      categories indolent systemic mastocytosis, systemic mastocytosis with concomitant
      blood disease, aggressive systemic mastocytosis and mast cell leukemia. Clinical
      manifestations are caused by tissue infiltration by proliferating mastocytes and
      by release of mediators. The principal organs affected are the skin, bones,
      digestive tract, liver, spleen and lymph nodes. Diagnosis of mastocytosis is
      based on appropriate stains (Giemsa, toluidine blue) and immunophenotype features
      (tryptase, CD117, also known as c-KIT and stem cell factor receptor). Serum
      tryptase levels reflect the total mast cell burden. Treatment must prevent
      release of mast cell mediators (histamine antagonists, cromolyn sodium,
      corticosteroids, or leukotriene-receptor inhibitors), limit bone involvement
      (bisphosphonates) and reduce the number of circulating mast cells (interferon,
      cladribine, or tyrosine kinase inhibitors). Enhanced understanding of the
      pathogenic mechanisms (mutation of c-kit and platelet-derived growth factor
      receptor alpha has led to the development of targeted treatments, including new
      inhibitors of tyrosine kinase and of nuclear factor Kappa B.

PMID- 15988349
TI  - [Heerfordt's syndrome].

PMID- 15988350
TI  - [Ask more of an antibiotic to obtain the least].

PMID- 15988351
TI  - [Isotretinoin in danger! So are the dermatologists!].

PMID- 15988352
TI  - [Isotretinoin: compliance with recommendations in childbearing women].
AB  - INTRODUCTION: The aim of this survey is to ascertain if the incidence of
      isotretinoin exposed pregnancies was reduced by the late recommendations of
      prescription and issue (AMM modification on 06/08/2001 and 25/09/2001). METHODS:
      All isotretinoin exposed pregnancies registered by the French Regional Drug
      Monitoring Centres, the Information Centre for Teratogenic Agents and Roche
      (Roaccutane), Pierre Fabre (Curacne Ge) and Expanscience (Procuta Ge)
      laboratories, from January 1st, 1999 to December 31st, 2002, were analysed.
      Enforcement of the strengthening of isotretinoin prescription recommendations was
      analysed on a sample of 68 prescriptions from 45 pharmacies throughout France.
      RESULTS: In 4 years, 103 isotretinoin exposed pregnancies (Roaccutane 97 p. 100,
      Curacne(R) Ge 3 p. 100) during teratogenic risk period, were registered.
      Pregnancy started less than one month after isotretinoin stopping (37 p. 100),
      during the treatment (43 p. 100), or was in progress when the treatment was
      initiated (20 p. 100). The reason of the 22 lacking contraception was known 12
      times, i.e. an absence of prescription (6 times), a refusal to take a prescribed
      contraception (3 times) and a self-medication (3 times). Among the 71 pregnancies
      whose contraceptive status is known, 48 p. 100 could had been avoided if
      recommendations had been followed (pregnancies due to a premature stopping or an
      absence of contraception). The issue of pregnancies is a voluntary termination in
      60 cases (87 p. 100). Malformations frequency is 25 p. 100. Incidence of
      isotretinoin exposed pregnancies remained stable, 0.26/1000 treated women (vs
      0.34 after 2001's AMM modifications). Of 68 prescriptions studied, 23 (24 p. 100)
      carried all the legal warnings, which is close to the previous survey's results.
      Contraception was in accordance with the recommendations in 78 p. 100 of cases
      and women learned and applied information given in 38 p. 100 of cases. At last,
      only 6 patients (9 p. 100) have both a correctly written prescription, a
      contraception and a time between the pregnancy test date and prescription and
      issue dates, in accordance with the licence and have had a correct information
      and understood it. Regarding the previous survey, pregnancy test before treatment
      was more often prescribed (96 p. 100 vs 88 p. 100). On the other hand, less women
      knew the necessity to keep on taking contraception one month after isotretinoin
      stopping (82 p. 100 vs 93 p. 100). CONCLUSION: Despite 3 successive isotretinoin
      prescription and issue recommendations strengthening in childbearing women,
      pregnancies can't be totally avoided. Bad compliance concerns the prescription
      and/or an incomplete or not understood information by the patient who does not
      scrupulously apply the care and contraception agreement. However, this study does
      not allow to assess the proportion of issued prescriptions despite their non
      accordance with the licence criteria. The National Commission of
      Pharmacovigilance did not like to limit isotretinoin prescription to
      dermatologists only. It estimates that the administrative authority must
      intensify information by dermatologists, general practitioners and pharmacists,
      about measures to take to avoid an exposure to isotretinoin during pregnancy.

PMID- 15988353
TI  - [Sensitive skin in France: an epidemiological approach].
AB  - INTRODUCTION: Sensitive skin is a frequently evoked cosmetic disorder, but its
      prevalence in France is unknown. METHODS: Using a survey of a representative
      sample of the French population aged over 15 carried out by ISPSOS-Sante, we
      assessed the frequency of sensitive skin. We used the quota method (gender, age,
      occupation of the head of the family) and stratification by area and category of
      the agglomeration. RESULTS: One thousand and six persons were surveyed. The non
      response rate was less than 1 p.cent. Fifty-two percent claimed they had
      sensitive or very sensitive skin. Women were predominantly concerned (59 vs. 44
      p.cent, p<0.0001). There was no significant difference between the socio
      professional categories. Twenty-eight p.cent of the population claiming their
      skin was very sensitive declared they had a concomitant dermatological disease,
      whereas 14 p.cent with sensitive skin, 7 p.cent with not very sensitive skin and
      2 p.cent with normal skin declared likewise. Skin sensitivity was triggered by
      emotion, cold, heat or cosmetics. A quality-of-life assessment using the SF-12
      scale showed significant alteration in the psychological dimension (but not
      physical) of the score for those with sensitive and very sensitive skin compared
      with the others, notably in the women (p<0.0001). DISCUSSION: This survey
      revealed a prevalence of sensitive skin in France equal to that found in England.
      It only measured the subjective feeling of sensitive skin experienced by those
      surveyed, since there was no clinical examination. The phenomenon appears
      frequent. Although women appeared to suffer more, a large proportion of men also
      suffered from sensitive skin.

PMID- 15988354
TI  - [Epidemic of Trichophyton tonsurans tinea capitis in a nursery school in the
      Southern suburbs of Paris].
AB  - INTRODUCTION: In March 2001 a school and family survey was conducted in a nursery
      school in the Southern suburbs of Paris, during an epidemic of Trichophyton
      tondsurans tinea. PATIENTS AND METHODS: One hundred twenty-nine children aged 3
      to 6 were examined as well as 15 adults working in the school. A survey of the
      contaminated children or asymptomatic carriers was performed. All the children
      and adults concerned were treated at the same time, without eviction from school.
      RESULTS: T. tonsurans was detected in 10 cases of tinea (7.7 p.cent of the
      persons examined), in 18 cases of cutaneous lesions (13.9 p.cent) and in 25
      asymptomatic carriers on the scalp (19.4 p.cent). The majority of the positive
      cases came from the same school class as the original case: 23 of the 26 children
      (88 p.cent), with 6 tinea, 14 asymptomatic carriers and 13 cutaneous lesions.
      Only one of the 15 adults exhibited a T. tonsurans cutaneous lesion. Among the 13
      families studied, 2 had several members involved, the first being that of the
      original case (3 tinea and 2 asymptomatic carriers). DISCUSSION: Several
      important points are underlined by this study: 1) the high contagiousness of T.
      tonsurans; 2) the detection of 2 mechanisms of indirect contamination (rag doll
      mascot in the class and the family hair-clipper); 3) the one-year time lapse
      between the arrival of the contaminating child in the class and the survey,
      explaining the extent of the contamination; 4) the underestimation of the
      epidemic due to the lack of mycological examinations; 5) the identification of
      several dermatophytes in the same school:M. canis, T soudanense and T. tonsurans,
      and 7) the futility of eviction from school when all the children can be treated.

PMID- 15988355
TI  - [Anti-H1 in dermatological practice].
AB  - INTRODUCTION: Histamine is an inflammation mediator that is fundamental for the
      development of some allergic reactions and is also implied in several common
      dermatological affections. Anti-H1s are molecules capable of couteracting the
      effect of histamine on its specific receptors. There are two types: first
      generation anti-H1 and second generation anti-H1. OBJECTIVE: To assess the
      efficacy of anti-H1 in the treatment of skin diseases. PATIENTS AND METHODS: A
      reference search was made using the Pubmed data bank. Critical analysis was made
      of the articles selected based on their evidence. RESULTS AND CONCLUSION:
      Demonstration of the efficacy of anti-H1 was only confirmed in a few dermatitis.
      Urticaria is the indication of choice. The symptomatic use of anti-H1 may be
      justified within the context of other dermatitis. The second rather than the
      first generation molecules should be preferred because of the lesser side effects
      and improved pharmacokinetic profile.

PMID- 15988356
TI  - [Incomplete expression of PHACE (S) syndrome: facial hemangioma associated with
      absence of the internal carotid artery].
AB  - INTRODUCTION: Hemangiomas are the most common benign tumors in childhood. In rare
      cases, they can be associated with dysmorphic malformations. The acronym, the
      PHACE (S) syndrome, was recently described by Frieden et al. in 1996 as a large
      facial or cervical Hemangioma, associated with one or more of the following
      systemic abnormalities including:Posterior fossa malformation, Arterial
      abnormalities, Coarctation of the aorta and/or cardiac defects, Eye abnormalities
      and Sternal clefts. CASE REPORT: A 2 year-old girl presented with a large left
      hemifacial hemangioma. The rest of the clinical examination was normal.
      Initially, simple clinical surveillance was scheduled. The outcome was good with
      almost complete regression of the hemangioma by the age of 8. However, there were
      remains to the left of the upper lip and plastic surgery was scheduled. Pre
      operative conventional arteriography revealed the complete, asymptomatic, absence
      of the ipsilateral internal carotid artery. Cerebral MRI and cardiac
      ultrasonography were normal. In the absence of somatic manifestations, regular
      clinical surveillance was decided on. DISCUSSION: Large facial or cervical
      hemagiomas can be associated with one or more systemic abnormalities described by
      the PHACE (S) acronym. Its prevalence is unknown, but is shows marked female
      preponderance. Among the systemic abnormalities, neurological and cardiac
      malformations predominate. Hence the PHACE (S) syndrome must be recognized.
      Moreover, in patients presenting with large facial or cervical hemangioma, the
      following examinations should be performed: neurological examination and cerebral
      MRI to rule out abnormality of the posterior fossa, completed by a sequence of
      angio-MRI in the search for cerebral artery malformations; cardiovascular
      exploration, completed by echocardiography in the case of doubt and examination
      of the eyes and sternum. Lastly, the enhanced risk of laryngeal sub-glottis
      hemangioma should be kept in mind.

PMID- 15988357
TI  - [Hypopigmented mycosis fungoides].
AB  - INTRODUCTION: Hypopigmented mycosis fungoides is a rare clinical form of the
      disease, first described in 1978. Since then, only a hundred odd cases have been
      documented. CASE REPORT: A young 19 year-old African woman had presented with
      hypochromatic macules since the age of 9 and for which the diagnostic enquiry had
      finally concluded in hypopigmented mycosis fungoides. DISCUSSION: The
      particularities of this form of mycosis fungoides, grade I according to the TNM
      classification, are principally its onset in black-skinned persons or of Asian
      origin, and the age of early onset with a predominance of pediatric cases. Its
      course is indolent for several years and thus source of delayed diagnosis. The
      differential diagnoses to be evoked are basically vitiligo, achromate eczematides
      and parapsoriasisis. The post-inflammatory depigmentation, frequent in black
      skinned subjects, is only an eliminating diagnosis. Its treatment is that of
      classical Grade I mycosis fungoides: topical mechlorethamine, phototherapy and
      topical corticosteroids.

PMID- 15988358
TI  - [Demodecidosis in a patient infected by HIV: successful treatment with
      ivermectin].
AB  - INTRODUCTION: Demodex is a saprophyte parasite in mammals. In Man, it is
      associated with differing clinical profiles (rosacea-like dermatitis,
      folliculitis and blepharitis). We report a case of demodecidosis in an HIV
      infected patient that was successfully treated with ivermectin. CASE REPORT: A
      man from Laos, infected by HIV and treated for glandular tuberculosis, presented
      with a prurigenous eruption on the face and the pre-sternal and interscapular
      areas. Direct examination of scraped product and histopathological examinations
      confirmed the diagnosis of demodecidosis. Clinical cure was obtained after 2
      single cures of ivermectin a one month's distance. DISCUSSION: The features of
      demodecidosis are often similar to those of rosacea. In immunodeficient patients,
      the semiology remains the same but the eruption is more abundant. During HIV
      infection, demodecidosis occurs at the AIDS stage or with a CD4 count lower than
      200/mm3. Many anti-dust mite molecules are used to treat the disease but
      frequently lead to irritation. Administration of a single cure of ivermectin,
      repeated if necessary, appears to be an interesting alternative to contact anti
      dust mite agents.

PMID- 15988359
TI  - [Actinomycosis of the buttock].
AB  - INTRODUCTION: Cutaneous actinomycosis of the buttocks is a rare granulomatous
      bacterial infection that usually starts in the perianal area. We present an
      exceptional case in the form of a pseudo-tumor. CASE REPORT: A 69 year-old woman,
      in general good health, developed an indurate mass on the supra-external quadrant
      of the right buttock. The tumor was centered by an ulcerated nodule with a
      diameter of around 10 centimeters. Imaging showed invasion of the soft tissue of
      the skin in the internal psoas muscle, the adipose tonality of which was
      compatible with a liposarcoma. The skin biopsy revealed characteristic bacterial
      grain in the center of a cholesterol granuloma. Subsequent culture in aerobic
      milieu identified Actinomyces gerencseriae. Cure was obtained following complete
      exeresis of the fibrous tissue and 8 months of antibiotic amoxicillin-clavulanic
      acid therapy. DISCUSSION: Other than the most unusual clinical aspect, the
      originality of this case of actinomycosis of the buttocks is based on its
      potential appendix origin, 4 years after acute appendicitis, with slow posterior
      fistulation. Other cases of actinomycosis of appendix origin have been reported
      and its delayed onset following the intervention has been documented. The pseudo
      sarcomatous aspect was responsible for diagnostic wandering. The histological
      image and, subsequently, the results of the bacteriological culture confirmed the
      diagnosis.

PMID- 15988360
TI  - [Spontaneous cholecystocutaneous fistula].
AB  - INTRODUCTION: Spontaneous cholecystocutaneous fistula is now a rare entity due to
      the advent of antibiotics, ultrasonography, and safe and early surgical treatment
      of biliary tract diseases. Such a case is reporting here, revealed by the
      systematic histological examination of the skin biopsy. OBSERVATION: A 65 year
      old male presented with an inflammatory and ulcerated lesion located on his right
      flank, with a long-standing but asymptomatic course. Biological tests and biliary
      tract ultrasonography were not very contributive. Histopathological findings
      consisted in a granulomatous dermal reaction enclosing biliary fragments. Per
      operative data were in favour of a compound biliocutaneous fistula complicating
      an inflammatory process of the gall-bladder. DISCUSSION: Spontaneous
      cholecystocutaneous fistula is unusual. Diagnosis might be difficult because of
      the lack of clinical specificity and a occasionally insidious evolution.
      Consequently, systemic histological examination is fundamental.

PMID- 15988361
TI  - [Capillary malformations associated with cerebral cavernous malformation].
AB  - INTRODUCTION: Capillary malformations such as benign hereditary telangiectasia
      are a familial affection, of dominant autosomal transmission, characterized by
      the progressive development of cutaneous telangiectasia during childhood. The
      association with cutaneous vascular, arteriovenous or lymphatic malformations is
      exceptional and has only recently been described. CASE REPORT: A 5 year-old girl
      presented with widespread erythematous, predominantly telangiectasic, congenital
      and acquired macules when she was one year-old. Her history was marked by right
      temporal cerebral hemorrhage at the age of 4, revealing a right temporal
      cavernoma-like vascular malformation. The familial history of telangiectasic
      macules and clinical and histological examination led to the diagnosis of benign
      hereditary telangiectasia. DISCUSSION: This case report raises doubt on the
      exclusively cutaneous nature of benign hereditary telangiectasic-type capillary
      malformations. Moreover, it illustrates the possibility of a particular clinical
      form of this affection, associating classical telangiectasia and post-wine stain
      type macules. The recent localization of the locus implied in this affection in
      5q14 in the same chromosomic space as the CMC1 locus incriminated in familial
      capillary malformations, suggests that these two affections are in fact phenotype
      variations of a single and same clinical entity.

PMID- 15988362
TI  - [Erosive pustulosis of the scalp: 3 cases].
AB  - BACKGROUND: Erosive pustulosis of the scalp is a rare entity of unknown etiology
      mainly affecting elderly people. It is often triggered by local trauma and
      features chronic pustules of the scalp evolving toward scarring alopecia. Its
      treatment is not yet codified. OBSERVATIONS: Two patients (66 and 87 years old)
      presented with crusted and erosive pustules of the scalp following surgical
      removal of actinic keratosis and total skin graft. In a third patient, similar
      lesions appeared after hair grafting. Clinical features were consistent with the
      clinical pattern of erosive pustulosis of the scalp. In all three patients, oral
      zinc gluconate in combination with topical steroids associated resulted in
      significant improvement. CONCLUSION: An association of topical steroids and oral
      zinc gluconate might be an interesting therapeutic option in this chronic, often
      disabling affection.

PMID- 15988363
TI  - [Atopic dermatitis: comparison of prevalence in France and Tunisia].

PMID- 15988364
TI  - [Trichophyton soudanense infection in two young girls].

PMID- 15988365
TI  - [The "one hand--two feet" syndrome in Algeria].

PMID- 15988366
TI  - [Acral papules: a clinico pathological review].

PMID- 15988367
TI  - [Symptomatic treatment of pruritus].

PMID- 15988368
TI  - [Allergy to methyldibromoglutaronitrile (dibromodicyanobutane)].

PMID- 15988369
TI  - [Spitz naevus].

PMID- 15988370
TI  - [Troubles in keratinization disorders: news].

PMID- 15988371
TI  - [Post traumatic mucosal ectopia of the eyelid].

PMID- 15988372
TI  - [Granulocytic sarcoma ("chloroma")].

PMID- 15988374
TI  - [Allergy to lanolin: myth or reality?].

PMID- 15988373
TI  - [Methoxypsoralene plus UVA and unexpected side effects].

PMID- 15988377
TI  - [RET mutations and preventive treatment of medullary thyroid cancer].

PMID- 15988378
TI  - Genetic testing for pheochromocytoma-associated syndromes.
AB  - Pheochromocytoma and paraganglioma are tumors of the autonomic nervous system.
      Various syndromes have been found to be associated with the development of
      pheochromocytomas and paragangliomas: multiple endocrine neoplasia type 2 (MEN 2,
      susceptibility gene: RET), von Hippel-Lindau disease (VHL, susceptibility gene:
      VHL), neurofibromatosis 1 (NF 1), and paraganglioma syndromes type 1, 3, and 4
      (susceptibility genes: succinate dehydrogenase gene, SDH, subunits D, C and B,
      respectively). Prevalence and clinical features of pheochromocytomas and
      paragangliomas are different for each of these syndromes. Mutational analysis of
      the susceptibility genes of these syndromes in patients presenting with
      pheochromocytoma or paraganglioma may help to judge the risks of multifocality of
      the tumor as well as development of malignant pheochromocytoma or of other
      malignant tumors. Here we review the recent progress in clinical characterization
      and genetic testing for these syndromes. Based on tumor characteristics and
      prevalence data we give recommendations for an efficient genetic testing
      procedure in patients presenting with pheochromocytomas and paragangliomas.

PMID- 15988379
TI  - [Pigmented micronodular dysplasia of the adrenal glands and Carney complex].

PMID- 15988380
TI  - Lessons from genes mutated in multiple endocrine neoplasia (MEN) syndromes.
AB  - Multiple endocrine neoplasia (MEN) types 1 and 2 syndromes are rare hereditary
      cancer syndromes expressing a variety of endocrine and non-endocrine neoplasias
      and lesions. The improving of both molecular and clinical genetics knowledge
      helps health care providers in the whole spectrum of the clinical managements of
      MEN patients. The MEN1 gene, a tumour suppressor gene, is responsible of MEN1
      syndrome, and is probably involved in the regulation of several cell functions,
      including DNA replication and repair and transcriptional machinery. RET proto
      oncogene encodes for a receptor tyrosine kinase protein whose expression is
      fundamental for appropriate migration, development and differentiation of
      neuroendocrine cells originating from neural crest. Currently, DNA testing makes
      possible the early identification of germline mutation in asymptomatic mutant
      gene carriers in both MEN syndromes. Consequently, the combination of new genetic
      and diagnostic tools could permit a precocious detection of MEN-associated
      neoplasms, and in particular the identification of a strong genotype-phenotype
      correlations in MEN2 syndrome demonstrates an improving outcome and quality of
      life for affected subjects.

PMID- 15988381
TI  - [Contribution of genetic testing after diagnosis of hypocalcemia].
AB  - Serum calcium is a fine-tuned biological value. In recent years, fundamental
      research and study of molecular anomalies causing certain hereditary diseases of
      phosphocalcium metabolism have greatly contributed to our knowledge of the
      factors involved in this regulation, from the embryogenesis of the parathyroid
      glands to the assay value of serum calcium. Targeted research on these genetic
      anomalies would be useful not only for the clinician, but also for the patient,
      contributing to the etiological search, patient follow-up, and possibly to
      antenatal diagnosis. The main genetic anomalies identified to date are: CaSR,
      GNAS, AIRE, VDR, mitochondrial DNA, 22q11 deletion.

PMID- 15988382
TI  - [Genetic anomalies of the androgen receptor and sexual ambiguity with normal
      testicular function at birth].

PMID- 15988383
TI  - 21-Hydroxylase deficiency: an exemplary model of the contribution of molecular
      biology in the understanding and management of the disease.
AB  - Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders
      caused by mutations in genes encoding the enzymes involved in one of the various
      steps of adrenal steroid synthesis. Steroid 21-hydroxylase deficiency (21-OHD) is
      responsible for over 95% of the 5 forms of CAH, and results due to enzymatic
      defect owing to mutation in the CYP21 gene. The disease has two major clinical
      presentations. The "classical" form is severe, and divided into a salt wasting
      (SW) and simple virilizing (SV) subgroups. In both, affected female fetuses
      undergo virilization of the external genitalia prenatally and present at birth
      with sexual ambiguity. In addition, in both sexes infants with SW CAH are at risk
      of life-threatening adrenal crisis without treatment. This is why it is so
      important to make a diagnosis and to counsel the families. The diagnosis is easy
      by measuring the plasma levels of 17-hydroxyprogesterone (17-OHP) in antenatal
      (amniotic fluid), or perinatal samples (peripheral blood). Confirmation by
      molecular genetic analysis is advised. The second form of 21-OHD is called "non
      classical" because the presentation is much less severe and the onset of clinical
      expression occurs long after birth, often in the peripubertal period, as non
      specific symptoms of hyperandrogeny. The unambiguous diagnosis of the latter
      requires a simple short ACTH test, with the measurement of 17-OHP at 60 min. In
      both forms, the mutations on the gene CYP21 responsible for the disease are now
      well known and can be identified by molecular biology techniques. There is a good
      correlation between phenotypes and genotypes, due to variable amount of the 21
      hydroxylase-enzyme activity left (null to 50-60%). SW, SV and NC forms are
      associated with distinct mutations or combination of mutations. Nowadays, by
      combining hormonal and molecular tests, it is possible to predict the clinical
      form of the disease in a given family in the context of a prenatal diagnosis,
      which can lead to a prenatal treatment. Therefore, 21-OHD genotyping also appears
      essential for a new approach of genetic counseling, prediction of clinical form
      after postnatal screening and to define the post-ACTH 17-OHP values indicating
      the cut-off lines between NC, heterozygote and normal subjects.

PMID- 15988384
TI  - The role of SF1/DAX1 in adrenal and reproductive function.

PMID- 15988385
TI  - [Familial aspect of primary hyperaldosteronism: analysis of families compatible
      with primary hyperaldosteronism type 2].

PMID- 15988386
TI  - Genetics of ACTH insensitivity syndromes.
AB  - The last decade has seen remarkable progress in our understanding of the genetic
      causes of these potentially lethal conditions. Clearly, other genes that cause
      FGD remain to be discovered, and further work is required on the functions of
      MRAP and ALADIN in the expectation that they will provide insights into essential
      biological processes and perhaps identify key therapeutic strategies and targets
      for these diseases.

PMID- 15988387
TI  - [Genetics of anterior hypopituitary diseases].

PMID- 15988388
TI  - Inactivating and activating mutations of the Gs alpha gene.

PMID- 15988389
TI  - Syndromes of thyroid hormone resistance.
AB  - Thyroid hormone resistance (RTH) is a rare autosomal dominant disorder,
      characterized clinically by goiter and biochemically by elevated circulating free
      thyroid hormone levels in the presence of measurable serum TSH concentrations.
      About 85% of patients with RTH are harboring mutations in thyroid hormone
      receptor beta (TRB). These mutations cluster in three different "hot spot" in the
      T3 binding domain of the receptor. When mapped to their homologous residues in
      the TR crystal structure, these three clusters of mutations border the T3-binding
      pocket. As a consequence, most TRB mutations impair the hormone binding to the
      receptor and interfere with the mechanism(s) of corepressor release and the
      consequent recruitment of coactivators. Thus, the remodeling of chromatin
      structure throughout the process of histone acetylation is prevented and the
      transcriptional activity of the mutant receptor on both positively and negatively
      regulated genes, severely disrupted. The lack of interaction with coactivators
      appears to be an additional mechanism for the dominant negative effects of mutant
      TRB on the transcriptional activity of the normal receptor.

PMID- 15988390
TI  - [Laminopathies: lipodystrophies, insulin resistance, syndromes of accelerated
      ageing... and others].
AB  - Laminopathies are a group of diseases due to mutations of type A-lamins, a group
      of proteins lining the inner aspect of cell nuclei. These diseases illustrate the
      complexity of the genotype-phenotype relationship characteristic of same genetic
      diseases. Since the discovery of the causal role of LMNA gene mutations in the
      genesis of Emery Dreifuss muscular dystrophy in 1999, no less than eight other
      diseases have been associated with mutations of this same gene! The tissue
      specific nature of the clinical manifestations, contrasting with the ubiquitous
      expression of these proteins, has incited much research concerning the
      physiological role of lamins, considered to be much broader than the structural
      function initially put forward. Certain laminopathies, which combine insulin
      resistance, android distribution of adipose tissue, dyslipidemia, early
      atherosclerosis, and hepatic steatosis, appear very similar though more severe to
      the frequent dysmetabolism syndrome. The relationships of laminopathies with
      accelerated aging syndrome, Hutchinson-Gilford progeria, or progeroid syndromes,
      which are also related to A/C lamin anomalies, could provide new avenues of
      research on the pathogenesis of the metabolic syndrome. In addition, clinicians
      have to be aware of atypical and milder forms of laminopathies, that require
      specific investigations and molecular screening of relatives allowing an adequate
      medical management.

PMID- 15988391
TI  - [Monogenic diabetes: a useful dimension for diabetology practice].
AB  - The number of identified monogenic diabetes progressively increases with time
      even if these forms of diabetes represent less than 5% of the cases. Every
      monogenic diabetes is characterized by an impairment of Beta cell at various
      levels. They are good models of diabetes-prone mechanisms. Diabetologists should
      recognize these forms because the management of the patients could be modified as
      a function of the genetic anomaly, in terms of either choice of hypoglycaemic
      agents, prognostic, management of associated manifestations or genetic
      counselling.

PMID- 15988392
TI  - [Psychological aspects of genetic diagnosis of endocrine tumors].

PMID- 15988393
TI  - [Molecular genetics in endocrinology].

PMID- 15988394
TI  - [Genetic testing, the legal setting in France and Europe].

PMID- 15988395
TI  - [The Paris experience in preimplantation genetic diagnosis: evaluation after the
      first births].
AB  - OBJECTIVE: To report the birth of the first thirteen infants conceived after
      preimplantation genetic diagnosis (PGD) within the medical assistance federation
      of Paris. PATIENTS AND METHODS: Fifty-nine couples were enrolled between January
      2000 and July 2001. They had a total of 71 oocyte pick-up cycles. The collected
      oocytes were inseminated by intracytoplasmic sperm injection. The resulting
      embryos were biopsied on the third day of development and the genetic analysis
      was performed on the same day. Most of the embryo transfers were carried out on
      the fourth day. RESULTS: The 71 oocyte pick-up cycles yielded 872 oocytes of
      which 731 were suitable for intracytoplasmic sperm injection. 421 embryos were
      biopsied and genetic diagnosis was obtained from 312 (74%) of these. 127 embryos
      were transferred during the course of 58 transfer procedures. There were 18
      biologic and 12 clinical (7 singles, 4 twins and 1 triple) pregnancies. Thirteen
      infants have been born and 4 are expected. CONCLUSIONS: PGD has gained a place
      among the choices offered to couples at risk of transmission of a serious and
      incurable genetic disease.

PMID- 15988398
TI  - Colonoscopy preparations.
AB  - Polyethylene glycol solutions versus sodium phosphate in preparing the bowel for
      colonoscopy.

PMID- 15988399
TI  - CYP3A and drug interactions.

PMID- 15988400
TI  - Pegaptanib sodium (Macugen) for macular degeneration.

PMID- 15988401
TI  - Thyrotoxicosis and the cardiovascular system.
AB  - Thyrotoxicosis is associated with increased cardiovascular morbidity and
      mortality, primarily due to heart failure and thromboembolism. Palpitations,
      caused by sinus tachycardia and occasionally by atrial fibrillation, are the most
      frequent cardiovascular symptom. As atrial fibrillation may be the only
      manifestation of thyrotoxicosis, thyroid hormone excess should routinely be
      excluded in patients with this rhythm disturbance. Heart failure occurs mostly in
      the presence of underlying heart disease or tachycardia-induced cardiomyopathy in
      patients with long-standing atrial fibrillation. On occasion, long-standing
      hyperthyroidism may lead to heart failure even in the absence of concomitant
      cardiac conditions. Beta-blockers offer symptomatic relief and at the same time
      slow the ventricular response in patients with atrial fibrillation. Amiodarone,
      and occasionally iodinated contrast agents, may cause iodine-induced
      thyrotoxicosis. Clinical suspicion is essential in the diagnosis of amiodarone
      induced thyrotoxicosis (AIT), because the antiadrenergic effect of the drug may
      conceal symptoms. AIT should be considered in any patient on amiodarone in the
      presence of new-onset or recurrent atrial arrhythmias or unexplained weight loss.
      Beyond discontinuation of amiodarone, treatment options include propylthiouracil
      or methimazole, potassium perchlorate, steroids, lithium and, if pharmacological
      treatment fails, surgery. Amiodarone may potentially be used less frequently in
      the future since recent studies have shown that this drug is inferior to
      implantable cardioverter defibrillators in prevention of sudden cardiac death in
      patients with severe heart failure. In addition, non-iodinated amiodarone
      analogues are currently in advanced phase of clinical testing.

PMID- 15988402
TI  - [Treatment of patient having thyroid nodules: dimension of disease, diagnostic
      choices and guide-lines].
AB  - The demand of nodule thyroid diagnosis has increased very much in the last years,
      because of large diffusion of medical information among the population, the
      increased use and improvement of medical technology that evidences more and more
      morphology alterations of the gland. The prevalence of palpable thyroid nodule is
      2.1-4.2%, but when the ultrasonography is used the prevalence can reach in
      average 67%. The thyroid cancer however is a rare event: 1% of all malign
      tumours. The medium incidence is 2.1 for 100,000 men per year, and 5.19 for
      100,000 women per year. pretest illness low probability presents a necessity of a
      very accurate diagnostic test. The introduction of FNA in the 70 has changed the
      diagnosis, and allowed to spare time and money. The patient with thyroid nodules
      should be evaluated by experienced physicians in the thyreopathy field, using
      efficient remote and family anamnesis, by an accurate palpation of the thyroid
      and the neck, cl AIM: ing necessary diagnostic controls. The physician should
      perform the FNA with a cytopathologist and should convey to him all the clinical
      and biotumoral information. He should be able to interpret correctly the results
      of the FNA and to suggest the diagnostic and therapeutical follow-up. This review
      reveals the best compromise between cost-effectiveness, based on the evidence
      results taken from international literature, taking into consideration various
      diagnostic opportunities at our disposal. Guide-lines for the treatment of
      patients with thyroid nodule are proposed.

PMID- 15988403
TI  - Thyroid disease in pregnancy and childhood.
AB  - The subject of thyroid disease in pregnancy is receiving increasing attention
      from many scientific disciplines. Thyroid function in pregnancy is characterised
      by a T4 surge at 12 weeks declining thereafter. Serum thyroid hormone
      concentrations fall in the second half of pregnancy but there are few data on
      normal reference ranges. Fetal brain development depends on T4 transport into the
      fetus which in turn depends on sufficient maternal iodine supply. There is
      current concern that adequate iodisation is not present in large parts of Europe.
      There is increasing evidence that thyroid autoimmunity is associated with fetal
      loss but the mechanism is unclear and therapy requires carefully conducted
      studies. While hyperthyroidism in pregnancy is uncommon, effects on both mother
      and child are critical if untreated. The use of propylthiouracil is recommended
      together with measurement of TSH receptor antibodies at 36 weeks gestation. Women
      receiving thyroxine therapy for hypothyroidism or as suppressive therapy should
      have their dose increased by up to 50% during pregnancy. There are now
      substantial data to show deleterious effects on child IQ resulting from low
      maternal T4 (or high TSH) during gestation. Major advances in molecular biology
      have contributed to elucidation of many genetic causes of congenital
      hypothyroidism. However, the aetiology of the majority of cases is still unclear
      and further research is required. The presence of TPO antibodies in about 10% of
      pregnant women in early gestation is a predictor of an increased incidence of
      subclinical hypothyroidism during pregnancy and also of postpartum thyroid
      dysfunction. The latter condition occurs in 5-9% of women and 25-30% progress to
      permanent hypothyroidism. This review suggests that screening for thyroid
      function in early pregnancy and levothyroxine intervention therapy for maternal
      subclinical hypothyroidism should be considered but evidence is awaited.
      Screening for both thyroid dysfunction and thyroid antibodies ideally at a
      preconception clinic but certainly in early gestation is recommended.

PMID- 15988404
TI  - [Methimazole versus methimazole and diphosphonates in hyperthyroid and
      osteoporotic patients].
AB  - AIM: It is well-know that hyperthyroidism is one of the key causes of secondary
      osteoporosis. High values of thyroid hormones increase the bone mineral turnover
      speed by promoting osteoclastic and osteoblastic activities. The aim of our study
      is to evaluate the increase of bone mineral density (BMD) in osteoporotic and
      hyperthyroid patients treated with only antithyroid drugs versus patients treated
      with antithyroid drugs and diphosphonates. METHODS: Twenty-six elderly male
      patients, 65-75 years, were selected. In all these patients, thyroid function
      (FT3, FT4, TSH, Tg, AbTg, AbTPO) was evaluated at baseline and after 6 and 12
      months from the start of medical treatment; the following were evaluated: BMD,
      calcium serum, phosphorus serum, alkaline phosphatase, PTH and 24 hours urinary
      calcium, phosphorus and hydroxyprolin. Thirteen patients (group 1) were treated
      with antithyroid drugs (methimazole 5-20 mg/die/os) and diphosphonates
      (alendronate 10 mg/die/os). The control group of 13 patients (group 2) was
      treated with antithyroid drugs only. RESULTS: After 6 months of treatment, the
      patients of group 1 showed a mean increase of 2.5% in lumbar spine BMD compared
      with a mean increase of 0.3% in group 2 (p<0.01). After 12 months, group 1 showed
      a mean increase of 6.2% in lumbar spine BMD, compared with a mean increase of 2%
      in group (p<0.001). CONCLUSIONS: The combination of antithyroid and
      diphosphonates drugs appears to be more efficacious than antithyroid therapy
      alone for the treatment of osteoporosis in male hyperthyroid patients.

PMID- 15988405
TI  - [Effect of long-term treatment with octreotide-lar in a TSH-secreting pituitary
      macroadenoma and secondary hyperthyroidism].
AB  - A 74 year-old man was admitted to the hospital for heart failure and atrial
      fibrillation episodes. He had been irregularly treated for hyperthyroidism during
      the previous 3 years, with poor control. Thyroid function evaluation showed
      secondary hyperthyroidism, with high free thyroid hormone levels and TSH
      inappropriately in the high-normal range (4.2 mU/ml), only slightly responsive to
      TRH-stimulation (6 microU/ml). Alpha-subunits were hyper-responsive to TRH
      stimulation (+123%). Thyroid autoimmunity tests were negative and ultrasonography
      evidenced a diffusely enlarged gland. Magnetic resonance (MR) imaging of the
      pituitary showed a macroadenoma. The patient underwent transphenoidal
      adenomectomy, and immunohistochemistry confirmed the diagnosis of a TSH-secreting
      pituitary macroadenoma. A moderate secondary hyperthyroidism was still present
      and a new MR evidenced residual disease, involving the right cavernous sinus. A
      (111)In-octreoscan revealed an increased captation in this area. The patient was
      treated with octreotide-Lar (20 mg/monthly), which normalized FT3, FT4 and TSH
      levels already after 3 months of therapy. This effect is still maintained at 42
      months of treatment. MR imaging showed a reduction in the residual lesion after
      18 months (>50% in comparison with postsurgical MR) and a further decrease after
      36 months of treatment). This suggests that the antiproliferative effect on the
      adenomatous cells is progressive and continues over time. This patients did not
      receive radiotherapy, so this action is entirely due to the medical treatment. No
      significant side effects developed and the patient's compliance was good. He has
      not had further arrhythmic episodes.

PMID- 15988406
TI  - Annual smoking-attributable mortality, years of potential life lost, and
      productivity losses--United States, 1997-2001.
AB  - Smoking harms nearly every organ of the body, causing many diseases and reducing
      quality of life and life expectancy. This report assesses the health consequences
      and productivity losses attributable to smoking in the United States during 1997
      2001. CDC calculated national estimates of annual smoking-attributable mortality
      (SAM), years of potential life lost (YPLL) for adults and infants, and
      productivity losses for adults. The findings indicated that, during 1997-2001,
      cigarette smoking and exposure to tobacco smoke resulted in approximately 438,000
      premature deaths in the United States, 5.5 million YPLL, and 92 billion dollars
      in productivity losses annually. Implementation of comprehensive tobacco-control
      programs as recommended by CDC can reduce smoking prevalence and related
      mortality and health-care costs.

PMID- 15988407
TI  - Heat-related mortality--Arizona, 1993-2002, and United States, 1979-2002.
AB  - Hyperthermia is the elevation of body temperature resulting from the body's
      inability to dissipate heat. Continued exposure to ambient heat close to body
      temperature (98.6 degrees F [37.0 degrees C]) contributes to a substantial number
      of deaths from hyperthermia, especially among elderly persons. To assess the
      health risk from hyperthermia, Arizona health practitioners and CDC researched
      cases of heat-related death and illness in Arizona, used U.S. death certificate
      data to summarize trends in heat-related deaths, and compared age-specific, heat
      related death rates in Arizona with those in the United States overall. Findings
      indicated that, during 1979-2002, a total of 4,780 heat-related deaths in the
      United States were attributable to weather conditions and that, during 1993-2002,
      the incidence of such deaths was three to seven times greater in Arizona than in
      the United States overall. Public health agencies in communities affected by
      periods of extreme heat should educate populations at risk (e.g., persons aged >
      or = 65 years) and consider designing and implementing location-specific heat
      response plans (HRPs).

PMID- 15988408
TI  - Update: Influenza activity--United States and worldwide, 2004-05 season.
AB  - During the 2004-05 influenza season, influenza A (H1),* A (H3N2), and B viruses
      cocirculated worldwide, and influenza A (H3N2) viruses predominated. In addition,
      several Asian countries continued to report widespread outbreaks of avian
      influenza A (H5N1) among poultry; in Vietnam, Thailand, and Cambodia, these
      outbreaks were associated with severe illnesses and deaths among humans. In the
      United States, the 2004-05 influenza season peaked in February, was moderate, and
      was associated predominantly with influenza A (H3N2) viruses. This report
      summarizes influenza activity in the United States and worldwide during the 2004
      05 influenza season.

PMID- 15988409
TI  - Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell
      expression of HB-EGF.
AB  - PURPOSE: To compare the gene expression pattern of control postmortem retinas
      with retinas from patients with proliferative vitreoretinopathy (PVR), to
      determine the expression of the heparin binding epidermal growth factor-like
      growth factor (HB-EGF) by glial cells in fibroproliferative membranes, and to
      examine whether cells of the human Muller cell line, MIO-M1, respond to HB-EGF
      with proliferation, migration, and secretion of the vascular endothelial growth
      factor (VEGF). METHODS: To identify genes that were differently expressed in PVR
      and control retinas, the RNA from the neural retinas of seven postmortem donors
      and of two patients with PVR were analyzed for differential gene expression, by
      hybridization of labeled cRNA probes to an Affymetrix human genome microarray
      set. The results were validated by real time PCR experiments investigating RNA
      from 6 postmortem retinas and 4 PVR retinas. Epiretinal PVR membranes were
      immunohistochemically stained for colocalization of HB-EGF and the glial cell
      marker, glial fibrillary acidic protein (GFAP). The HB-EGF evoked proliferation
      of cultured Muller cells was investigated by a bromodeoxyuridine immunoassay,
      chemotaxis was assessed with a migration assay, and the release of VEGF was
      evaluated by ELISA. RESULTS: Out of the 12,600 genes and expressed sequence tags
      investigated, the levels of 80 showed an increased expression, and 21 were
      expressed at decreased levels, in the retinas of PVR patients compared to the
      control retinas. The upregulated signals include genes for nuclear and cell cycle
      related proteins, extracellular secretory proteins, cytosolic signaling proteins,
      and proteins of the membrane and the extracellular matrix. The genes of the
      hepatocyte growth factor and of HB-EGF were found to be expressed in PVR retinas
      but not in control retinas. In epiretinal membranes of patients with PVR, HB-EGF
      immunoreactivity partially colocalized with GFAP. In cultured Muller cells, HB
      EGF stimulated both proliferation and chemotaxis, and the secretion of VEGF, via
      activation of the extracellular signal regulated kinases 1 and 2 and of the
      phosphatidylinositol-3 kinase. CONCLUSIONS: The development of PVR is accompanied
      by complex changes of the gene expression in the neural retina, with an
      upregulation of genes that support cell proliferation, cell signaling, cell
      motility, and extracellular matrix remodeling. HB-EGF is one of the factors that
      are significantly upregulated in PVR retinas. HB-EGF expression in
      fibroproliferative tissue and its stimulatory effect on glial cell proliferation,
      chemotaxis, and VEGF secretion suggest that HB-EGF may be a factor mediating
      glial cell responses during PVR.

PMID- 15988410
TI  - Neutrophils promote experimental choroidal neovascularization.
AB  - PURPOSE: To investigate the role of neutrophils in the development of laser
      induced experimental choroidal neovascularization (CNV). METHODS: CNV was induced
      by laser photocoagulation in adult male C57BL/6J mice. Neutrophil infiltration
      was evaluated by histology and confocal immunohistology. The expression of
      neutrophil chemotactic chemokines in the regions of laser injury was determined
      by quantitative real-time PCR. Animals were treated with NIMP-R14, an anti-murine
      neutrophil monoclonal antibody (mAb), intraperitoneally to deplete neutrophils.
      The specific neutrophil depletion was confirmed by flow cytometry. The CNV
      responses were compared between neutropenic and untreated control mice on the
      basis of fluorescein angiography (FA), CNV lesion volume and lesion histology,
      and vascular endothelial growth factor (VEGF) expression by ELISA. Expression of
      VEGF and Angiopoietin-1 and Angiopoietin-2 protein by murine neutrophils was
      evaluated by confocal immunohistochemistry. RESULTS: Neutrophils infiltrated the
      sites of laser injury as early as day 1 after laser treatment and peaked at day
      3. The neutrophil infiltration correlated with enhanced mRNA expression of
      neutrophil chemotactic chemokines MIP-2 and KC in the lesions. Administration of
      NIMP-R14 mAb specifically depleted neutrophils. Analysis of FA, CNV volume, and
      lesion histology, all demonstrated a moderate decrease in the CNV response in
      neutropenic mice compared to control mice (p<0.01). The reduction in the CNV
      response in neutropenic mice was associated with decreased VEGF protein levels in
      the ocular posterior segment. Murine neutrophils contained VEGF and Angiopoietin
      1 and Angiopoietin-2 proteins. CONCLUSIONS: Neutrophil invasion was part of early
      inflammatory responses during laser induced CNV. Neutrophil depletion correlated
      with reduced CNV responses and decreased VEGF protein expression. These data
      suggest that neutrophils promoted the early development of CNV possibly via
      secretion of angiogenic growth factors.

PMID- 15988411
TI  - Lentiviral mediated gene delivery to the anterior chamber of rodent eyes.
AB  - PURPOSE: To study the in vivo efficiency of lentiviral vectors in delivering
      genes to the trabecular meshwork (TM) of rodent eyes. METHODS: Lentiviral vectors
      were constructed using the elongation factor 1 alpha (EF-1alpha) promoter driving
      expression of the green fluorescent protein (GFP) gene. The viral construct was
      injected intracamerally through the peripheral cornea into the anterior chamber
      of live rodent eyes. Several variables were evaluated to determine the optimal
      conditions for TM cell transduction. These parameters included viral
      concentration, injection volume, needle rotation, and the modulation of anterior
      chamber current convections. Changes in intraocular pressures (IOPs) were
      monitored using a Tonopen XL. Signs of inflammation and corneal
      neovascularization were evaluated by slit lamp observation. Three weeks after
      injection, the eyes were enucleated and analyzed for GFP expression and
      distribution. RESULTS: A single intracameral viral dose between 10(7) and 10(8)
      pfu produced a high and evenly distributed expression of GFP in the TM and
      corneal endothelial cells. The cornea remained clear and no signs of inflammation
      were present during the course of the experiment. Moreover, no significant
      changes in IOPs were observed. CONCLUSIONS: A high transduction efficiency of TM
      and corneal endothelial cells can be effectively obtained after a single dose of
      recombinant lentivirus. The EF-1alpha promoter induces high expression of the
      reporter gene and is a reliable alternative to the CMV promoter when stable, long
      term expression is desired.

PMID- 15988412
TI  - Association between glaucoma and gene polymorphism of endothelin type A receptor.
AB  - PURPOSE: Endothelin 1 (ET-1), a potent vasoconstrictor, may affect regulation of
      intraocular pressure and ocular vessel tone. Thus, ET-1 and its receptors may
      contribute to development of glaucoma. We investigated whether gene polymorphisms
      of ET-1 (EDN1) and its receptors ETA (EDNRA) and ETB (EDNRB) were associated with
      glaucoma phenotypes and clinical features. METHODS: We studied 224 normal
      Japanese controls and 426 open angle glaucoma (OAG) patients including 176 with
      primary open angle glaucoma (POAG) and 250 with normal tension glaucoma (NTG).
      Nine single nucleotide polymorphisms were detected among the participants using
      the Invader assay; four for EDN1 (T-1370G, +138/ex1 del/ins, G8002A, K198N), four
      for EDNRA (G-231A, H323H, C+70G, C+1222T), and one for EDNRB (L277L). Genotype
      distributions were compared between normal controls and OAG. Age at diagnosis,
      untreated maximum intraocular pressure (IOP), and visual field defects at
      diagnosis were examined for association with polymorphisms. RESULTS: Of the 9
      polymorphisms, genotype distributions showed no significant differences between
      OAG patients and controls adjusted by age. The GG genotype of EDNRA/C+70G was
      associated with worse visual field defects in NTG patients (p=0.014; Mann-Whitney
      U test, and p=0.027; logistic regression analysis). CONCLUSIONS: The polymorphism
      of EDNRA/C+70G may be related to NTG risk factors.

PMID- 15988415
TI  - Peptic ulcer disease.

PMID- 15988417
TI  - Developing an efficient model to select emergency department patient satisfaction
      improvement strategies.
AB  - STUDY OBJECTIVE: Patient satisfaction is an important performance measure for
      emergency departments (EDs), but the most efficient ways of improving
      satisfaction are unclear. This study uses optimization techniques to identify the
      best possible combination of predictors of overall patient satisfaction to help
      guide improvement efforts. METHODS: The results of a satisfaction survey from
      20,500 patients who visited 123 EDs were used to develop ordinal logistic
      regression models for overall quality of care, overall medical treatment,
      willingness to recommend the ED to others, and willingness to return to the same
      ED. Originally, 68,981 surveys were mailed, and 20,916 were returned,
      representing an overall response rate of 30.3%. We then incorporated these
      regressions into an optimization model to select the most efficient combination
      of predictors necessary to increase the 4 overall satisfaction measures by 5%. A
      sensitivity analysis was also conducted to explore differences across hospital
      peer groups and regions. RESULTS: Results differ slightly for each of the 4
      overall satisfaction measures. However, 4 predictors were common to all of these
      measures: "perceived waiting time to receive treatment," "courtesy of the nursing
      staff," "courtesy of the physicians," and "thoroughness of the physicians." The
      selected predictors were not necessarily the strongest predictors identified
      through regression models. The optimization model suggests that most of these
      predictors must be improved by 15% to increase the overall satisfaction measures
      by 5%. CONCLUSION: This study introduces the use of optimization techniques to
      study ED patient satisfaction and highlights an opportunity to apply this
      technique to widely collected data to help inform hospitals' improvement
      strategies. The results suggest that hospitals should focus most of their
      improvement efforts on the 4 predictors mentioned above.

PMID- 15988418
TI  - Patient satisfaction and the curse of Kelvin.

PMID- 15988419
TI  - Images in emergency medicine. Dorsal dislocation.

PMID- 15988422
TI  - Emergency department HIV testing and counseling: an ongoing experience in a low
      prevalence area.
AB  - STUDY OBJECTIVE: Despite recommendations, emergency department (ED)-based HIV
      screening is not widespread, and feasibility studies are generally limited to
      settings with high HIV prevalence (>1%). This investigation was to evaluate an
      ongoing, publicly funded, ED-based HIV counseling and testing program in a low
      prevalence area. METHODS: We reviewed a database of patients treated by an ED
      based HIV counseling and testing program at a large, urban, teaching hospital for
      1998 to 2002. ED patients at risk for HIV were targeted for standard serologic
      testing and counseling. Data were collected prospectively using standardized
      forms as part of clinical operations rather than in the context of rigorous
      research methodology; patient-oriented outcomes were not assessed. Counselors
      were trained according to Centers for Disease Control and Prevention guidelines,
      and health department guidelines for counseling and testing centers were
      followed. The main outcome measure was the number and proportion of patients
      newly diagnosed with HIV. RESULTS: Eight thousand five hundred seventy-four
      patients were approached; 5,504 consented to HIV testing. Mean age was 29 years
      (SD 9.4 years), 76% were black, and 50% were men. Five thousand three hundred
      seventy-four (97.6%) patients tested negative and 39 (0.7%) patients tested
      positive. Seventy-five percent of negative-test patients and 79% of positive-test
      patients were notified of test results. Information for seropositive patients not
      notified of results was forwarded to the health department. All notified HIV
      positive patients entered treatment. Risk factors included sexually transmitted
      disease (47%), multiple sexual partners (40%), unprotected sex while using drugs
      or alcohol (30%), men having sex with men (5%), and intravenous drug use (4%).
      CONCLUSION: Identification of HIV-positive patients is possible in low-prevalence
      ED settings. In this instance, it was possible to perpetuate an ED-based HIV
      intervention program during an extended time. Although our work expands the
      profile of ED-based HIV counseling and testing beyond previous reports, the
      results should not be overgeneralized.

PMID- 15988420
TI  - Older emergency department patients with acute myocardial infarction receive
      lower quality of care than younger patients.
AB  - STUDY OBJECTIVE: We assessed the independent relationship between age and the
      quality of medical care provided to patients presenting to the emergency
      department (ED) with acute myocardial infarction. METHODS: We conducted a 2-year
      retrospective cohort study of 2,216 acute myocardial infarction patients
      presenting urgently to 5 EDs in Colorado and California from July 1, 2000,
      through June 30, 2002. Data on patient characteristics, clinical presentation,
      and ED processes of care were obtained from the ED record and ECG review.
      Patients were divided into 6 groups based on their age at the time of their ED
      visit: younger than 50 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, 80
      to 89 years, and 90 years or older. Hierarchic multivariable regression was used
      to assess the independent association between age and the provision of aspirin,
      beta-blockers, and reperfusion therapy (fibrinolytic agent or percutaneous
      coronary intervention) in the ED to eligible acute myocardial infarction
      patients. RESULTS: Of ideal candidates for treatment in the ED, 1,639 (80.5%) of
      2,036 received aspirin, 552 (60.3%) of 916 received beta-blockers, and 358
      (77.8%) of 460 received acute reperfusion therapy. After adjustment for
      demographic, medical history, and clinical factors, older patients were less
      likely to receive aspirin (odds ratio [OR] 0.85, 95% confidence interval [CI]
      0.77 to 0.93), beta-blockers (OR 0.79, 95% CI 0.71 to 0.88), and reperfusion
      therapy (OR 0.30, 95% CI 0.18 to 0.52). CONCLUSION: Older patients presenting to
      the ED with acute myocardial infarction receive lower-quality medical care than
      younger patients. Further investigation to identify the reasons for this
      disparity and to intervene to reduce gaps in care quality will likely lead to
      improved outcomes for older acute myocardial infarction patients.

PMID- 15988423
TI  - Clinical efficacy of racemic albuterol versus levalbuterol for the treatment of
      acute pediatric asthma.
AB  - STUDY OBJECTIVE: An efficacy treatment study is conducted comparing levalbuterol
      to racemic albuterol for acute pediatric asthma in the emergency department (ED).
      METHODS: This was a prospective, double-blind, randomized, controlled study
      involving 129 children (2 to 14 years), presenting to a pediatric ED with an
      acute moderate or severe asthma exacerbation. Children were treated using a
      standard ED asthma pathway. Primary outcomes were changes from baseline in
      clinical asthma score and the percentage of predicted forced expiratory volume in
      1 second after the first, third, and fifth treatment. Secondary outcomes included
      number of treatments, length of ED care, rate of hospitalization, and changes in
      pulse rate, respiratory rate, and oxygen saturation. Occurrence of adverse events
      was recorded. RESULTS: Sixty-four children in the racemic albuterol and 65
      children in the levalbuterol group completed the study. There were no differences
      between groups in primary outcomes, secondary outcomes, or adverse events.
      CONCLUSION: There was no difference in clinical improvement in children with
      acute moderate to severe asthma exacerbations treated with either racemic
      albuterol or levalbuterol.

PMID- 15988424
TI  - Comparison of 1- versus 2-person bag-valve-mask techniques for manikin
      ventilation of infants and children.
AB  - STUDY OBJECTIVE: We compare the mean tidal volumes per weight and peak pressures
      generated by the 1- and 2-person techniques of bag-valve-mask ventilation in a
      pediatric model. METHODS: This was a prospective, descriptive study in which
      postgraduate year 1, postgraduate year 2, and postgraduate year 3 pediatric
      residents, postgraduate year 2 emergency medicine residents, pediatric emergency
      department nurses, transport personnel, and paramedics were asked to perform 1-
      and 2-person bag-valve-mask ventilation on infant and child manikins.
      Participants were randomly assigned a partner and performed both techniques.
      Tidal volume and peak pressure were recorded every 15 seconds for 3 minutes by a
      blinded assistant. RESULTS: Seventy participants, 10 in each group, completed the
      study. Overall, for the infant- and child-manikin groups, the 2-person technique
      generated higher mean tidal volume per weight than the 1-person technique
      (infant: 7.2 versus 5.9; child: 8.8 versus 6.1). Overall, the 2-person technique
      generated higher mean peak pressures than the 1-person technique (infant: 27.4
      versus 22.0; child: 27.2 versus 21.8). Similar results were found among all
      provider groups. Paramedics were the only providers able to generate a
      recommended median tidal volume per weight of 10 mL/kg in the child manikin group
      when using either technique and were the only providers, when using the 2-person
      technique, to generate a mean tidal volume per weight of 10 mL/kg in the infant
      group. CONCLUSION: Two-person bag-valve-mask ventilation provided greater mean
      tidal volumes per weight and peak pressures in the infant- and child-manikin
      model compared with the 1-person technique.

PMID- 15988425
TI  - The efficacy of ketamine in pediatric emergency department patients who present
      with acute severe asthma.
AB  - STUDY OBJECTIVE: We determine whether a continuous infusion of ketamine can
      decrease the severity of a moderately severe acute asthma exacerbation by a
      clinically significant 2 points using a 15-point Pulmonary Index scoring scale.
      METHODS: A double-blinded, randomized, placebo-controlled trial was performed to
      evaluate patients aged 2 to 18 years who presented to a pediatric emergency
      department with an acute asthma exacerbation. Exclusion criteria included
      temperature greater than 39 degrees C (102 degrees F), focal infiltrate on
      radiograph, or any glucocorticoid use in the last 72 hours. Eligible patients
      received 3 treatments with albuterol, ipratropium bromide, and a dose of oral or
      parenteral glucocorticoids. If the Pulmonary Index score remained 8 to 14,
      enrollment proceeded. All enrolled patients received continuous nebulized
      albuterol at 10 mg/hour and were randomized to receive an intravenous bolus of
      0.2 mg/kg of ketamine, followed by a 2-hour ketamine infusion at 0.5 mg/kg per
      hour or an equal-volume regimen with normal-saline placebo. A Pulmonary Index
      score was performed on patients at 0, 30, 60, 90, and 120 minutes. RESULTS: Sixty
      eight patients were enrolled, with 33 randomized to the ketamine infusion and 35
      randomized to placebo. Mean ages of patients enrolled, chronic severity of
      asthma, and duration of symptoms before presentation were similar between groups.
      At enrollment, the mean Pulmonary Index score in the placebo group was 10.3+/-1.1
      versus 10.5+/-1.5 for the ketamine group (difference of means 0.2; 95% confidence
      interval [CI] -0.5 to 0.8). Sixty-two patients completed the entire 2-hour
      infusion protocol. No significant difference between groups was seen in rate of
      improvement in the Pulmonary Index score at completion. The mean decrease in the
      Pulmonary Index scores at the end of the infusion was 3.6+/-1.3 in the placebo
      group versus 3.2+/-2.0 in the ketamine group (difference of means 0.4; 95% CI 
      0.4 to 1.3). No short-term adverse effects necessitating discontinuation of the
      infusion or adverse behavioral impacts at 48 hours after discharge were noted.
      CONCLUSION: We conclude that ketamine given at 0.2 mg/kg followed by an infusion
      of 0.5 mg/kg per hour for 2 hours provided no incremental benefit to standard
      therapy in this cohort of children with a moderately severe asthma exacerbation.

PMID- 15988426
TI  - Xanthrochromia? By what method? A comparison of visual and spectrophotometric
      xanthrochromia.
AB  - STUDY OBJECTIVE: Most US hospitals use visual inspection for the detection of
      cerebrospinal fluid xanthrochromia. We compared visual inspection with
      spectrophotometric xanthrochromia and studied the effect of tube diameter on the
      sensitivity of visual inspection. METHODS: Blinded, experienced laboratory
      technicians visually examined unmarked samples to determine the presence or
      absence of xanthrochromia. Samples were prepared by lysing RBCs in distilled
      water. Serial dilutions were placed in clear polystyrene tubes obtained from
      standard lumbar puncture trays. Laboratory technicians were asked to examine each
      sample for xanthrochromia using visual inspection. Next, they were asked to
      interpret the same set of samples with the assistance of a threshold standard.
      Last, they were asked to interpret the same dilutions, but this time presented in
      a larger-diameter tube. The absorbance of each sample was measured in a double
      beam spectrophotometer at wavelengths between 300 and 700 nm. Samples were said
      to demonstrate spectrophotometric xanthrochromia if they had an absorbance
      greater than 0.023 at 415 nm. RESULTS: Sixteen laboratory technicians were shown
      a total of 160 samples, of which 64 (40%) demonstrated spectrophotometric
      xanthrochromia. Visual inspection of the samples was 26.6% sensitive (95%
      confidence interval [CI] 16% to 38%) and 97.9% specific (95% CI 95% to 100%) for
      spectrophotometric xanthrochromia. Using a reference standard did not improve the
      performance of visual inspection, but increasing collection-tube diameter
      increased the sensitivity to 55% (95% CI 43% to 68%). CONCLUSION: Visual
      inspection is not sensitive for the detection of spectrophotometric
      xanthrochromia. Increasing the diameter of the collection tubes did improve
      sensitivity. Emergency physicians should be aware of how xanthrochromia is
      determined at their institutions and understand the implications of using visual
      detection to determine the presence or absence of xanthrochromia.

PMID- 15988427
TI  - Survey of emergency physicians about recombinant tissue plasminogen activator for
      acute ischemic stroke.
AB  - STUDY OBJECTIVE: The use of recombinant tissue plasminogen activator (rt-PA) for
      acute ischemic stroke is controversial among emergency physicians. We survey
      emergency physicians to determine (1) the proportion of emergency physicians
      resistant to using rt-PA in the ideal setting because of the risk of symptomatic
      intracerebral hemorrhage; (2) the proportion of emergency physicians resistant to
      using rt-PA in the ideal setting because of the perceived lack of benefit; (3)
      the highest acceptable symptomatic intracerebral hemorrhage risk; and (4) the
      lowest acceptable accompanying relative improvement in neurologic outcome.
      METHODS: The American College of Emergency Physicians randomly selected 2,600 of
      its active members for anonymous Web-based or paper survey. The proportion of ED
      physicians resistant to rt-PA use because of symptomatic intracerebral hemorrhage
      risk and perceived lack of benefit, in addition to the mean acceptable
      symptomatic intracerebral hemorrhage risk and associated benefit, was calculated
      with 95% confidence intervals (CIs). Multivariable logistic regression was used
      to identify factors independently associated with willingness to use rt-PA in the
      ideal setting. RESULTS: The median age of the 1,105 (43%) respondents was 44
      years. Overall, the mean upper limit of symptomatic intracerebral hemorrhage
      tolerable was 3.4% (95% CI 3.2% to 3.5%), with associated lowest acceptable mean
      relative improvement of 40% (95% CI 39% to 41%). Forty percent (95% CI 37% to
      44%) of physicians reported that they were not likely to use rt-PA. Of these, 65%
      (95% CI 61% to 69%) of physicians reported this was because of the risk of
      symptomatic intracerebral hemorrhage, 23% (95% CI 19% to 27%) reported the cause
      was the perceived lack of benefit, and 12% (95% CI 9% to 15%) reported both
      reasons were the cause. Independently associated with willingness to use rt-PA
      were female sex (odds ratio 2.30 [1.57, 3.36]) and previous use of rt-PA for
      stroke (3.13 [2.33, 4.17]). CONCLUSION: Symptomatic intracerebral hemorrhage risk
      is the factor most likely to preclude rt-PA use by emergency physicians. Of the
      40% of physicians who would not use rt-PA, about two thirds reported this was due
      to symptomatic intracerebral hemorrhage risk, and about a quarter of physicians
      cited the relative lack of benefit. Treatment trials that aim to reduce
      symptomatic intracerebral hemorrhage risk to 2% to 3% are likely to stimulate the
      interest of emergency physicians in the use of thrombolytics for acute ischemic
      stroke.

PMID- 15988428
TI  - Thinking globally, acting locally.

PMID- 15988429
TI  - Pontine hemorrhage presenting as an isolated facial nerve palsy.
AB  - We report a case of an isolated facial nerve palsy in a young, otherwise healthy
      man who was found to have a pontine hemorrhage on computed tomography. Pontine
      hemorrhage is a rare cause of facial nerve palsy and has been reported in the
      literature as an isolated neurologic finding in only 1 other instance. This case
      reminds the emergency physician to remain vigilant for alternative causes of
      facial nerve palsy other than "idiopathic" Bell's palsy.

PMID- 15988431
TI  - Epidemiology of epistaxis in US emergency departments, 1992 to 2001.
AB  - STUDY OBJECTIVE: The epidemiology of emergency department (ED) visits for
      epistaxis is unknown. We use national data to fill this gap and test hypotheses
      that epistaxis visits are more common with increasing age and in winter. METHODS:
      We identify ED visit with epistaxis from 10 years of the National Hospital
      Ambulatory Medical Care Survey. We calculate visit rates by age and other
      demographic characteristics and assess mode of arrival and disposition. Results
      are presented with 95% confidence intervals (CIs). RESULTS: From 1992 to 2001,
      epistaxis occurred at 4,503,000 ED visits, or 0.46% (95% CI 0.41% to 0.51%) of
      all visits. Per 1,000 population, 1.7 (95% CI 1.5 to 1.9) ED visits for epistaxis
      occurred annually. The age-related frequency was bimodal, with peaks among those
      younger than 10 years (4.0 per 1,000 visits) and aged 70 to 79 years (12.0 per
      1,000 visits). Most cases (83%; 95% CI 80% to 86%) were atraumatic. Traumatic
      cases were younger than atraumatic cases (mean age 31 versus 49 years). From
      December to February, atraumatic epistaxis occurred in 0.50% (95% CI 0.40% to
      0.60%) of all visits versus 0.34% (95% CI 0.30% to 0.39%) during nonwinter
      months. Fifteen percent (95% CI 12% to 18%) of cases arrived by ambulance, and 6%
      (95% CI 5% to 7%) of patients were hospitalized. CONCLUSION: Epistaxis accounts
      for about 1 in 200 ED visits in the United States. Although there is an early age
      peak (age >10 years), the frequency increases from age 20 years onward, with the
      highest rates in the elderly. Epistaxis visits are more common in the winter.
      Future efforts to decrease epistaxis visits might focus on education of the
      elderly and parents of young children about nasal mucosa care and basic
      approaches to home management.

PMID- 15988430
TI  - Evaluation of a brief intervention in an inner-city emergency department.
AB  - STUDY OBJECTIVE: This study tests the effect of a brief intervention with
      emergency department (ED) patients to reduce at-risk drinking. METHODS: We
      enrolled patients aged 18 years or older who screened positive for at-risk
      drinking in an urban academic ED and used alternative allocation to assign them
      to control or intervention status. A 20-minute, semiscripted, negotiated
      interview was conducted with the intervention group in English and Spanish by 3
      health promotion advocates (peer educators). The Alcohol Use Identification Test
      (AUDIT) was administered at baseline and 3 months after enrollment. RESULTS:
      Among 1,036 patients screened for at-risk drinking, 295 with CAGE questionnaire
      score greater than 1 and no alcohol treatment in the past year enrolled in the
      study and were randomly assigned to the control arm (n=151) or the intervention
      arm (n=144). Follow-up was achieved with 88 patients in the intervention group
      and 97 patients in the control group (63% of enrollees). Among the 185 patients
      followed up, 64% of the intervention group versus 80% of the control group scored
      greater than 7 on the follow-up AUDIT (scored on a scale of 1 to 40; P<.05, odds
      ratio [OR] 2.35, 95% confidence interval [CI] 1.21 to 4.55). Multinomial logistic
      regression analysis demonstrates, after controlling for demographic
      characteristics and other independent variables, that assignment to intervention
      status decreased the odds of at-risk (moderate) drinking as defined by AUDIT
      scores of 7 to 18 (OR 0.42, P<.05, 95% CI 0.19 to 0.91) but did not affect
      patients with AUDIT scores in the 19 to 40 range. CONCLUSION: Brief motivational
      intervention administered by peer educators to ED patients appears to reduce
      moderately risky drinking and associated problems.

PMID- 15988432
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug
      use, or other nonoccupational exposure to HIV in the United States.

PMID- 15988434
TI  - Evidence-based emergency medicine/rational clinical examination abstract. The
      clinical diagnosis of streptococcal pharyngitis.

PMID- 15988435
TI  - Evidence-based emergency medicine/rational clinical examination abstract.
      Clinical assessment for acute thoracic aortic dissection.

PMID- 15988436
TI  - The boy who cried unicorn: a parable.

PMID- 15988437
TI  - Images in emergency medicine. Emphysematous cholecystitis.

PMID- 15988438
TI  - 24/7: the next big thing?

PMID- 15988439
TI  - Is the initial diagnostic impression of "noncardiac chest pain" adequate to
      exclude cardiac disease?

PMID- 15988440
TI  - HIV postexposure prophylaxis in victims of child sexual abuse.

PMID- 15988442
TI  - Weighing the 480-pound person.

PMID- 15988443
TI  - Building capacity and competency in conducting health disparities research.

PMID- 15988444
TI  - The Social Security debate: considering aging, health disparities, and AAN
      stance.

PMID- 15988447
TI  - Transformation for health: a framework for health disparities research.
AB  - The task of generating knowledge addressing disparities in health among
      vulnerable populations in American society is explored. The community-based
      participatory approach as an alternate paradigm to traditional research is
      mentioned as a process for understanding the realities of the populations of
      interest. Identification and testing of mediating and moderating variables is
      suggested to guide the process of increasing knowledge regarding health
      disparities. Transformation for Health is proposed as a conceptual framework to
      study how these third variables influence the relationship between the primary
      variables of interest. A theoretical example is offered describing the
      application of the framework to study the mediators and moderators in an
      investigation of childhood obesity. Analytical challenges in the exploration of
      "third variables" are described, and the authors recommend that salient
      methodological issues should be addressed when conducting these types of
      investigations.

PMID- 15988448
TI  - Participatory action research to understand and reduce health disparities.
AB  - Participatory action research (PAR) is an excellent way to systematically learn
      about the conditions under which people experience health disparities, what it is
      like from the perspective of those experiencing such disparities and, even more
      importantly, how to ameliorate this major public health problem and create a more
      equitable and effective health care system. This article describes the method of
      PAR, supports the appropriateness of PAR to learn about and reduce health
      disparities, and then presents some specific examples of research projects that
      have employed or are planning to employ PAR. These examples are from the work of
      several authors of this article, who are members of an interdisciplinary working
      group that serves as a forum for discussion of issues related to qualitative
      research methods and facilitates the development of qualitative studies. All of
      the authors of this article are part of a task force of this working group that
      is focusing specifically on community outreach with the goal of reducing health
      disparities within specific communities.

PMID- 15988449
TI  - Developing and refining interventions in persons with health disparities: the use
      of qualitative description.
AB  - Eliminating health disparities by the year 2010 has become a clear priority for
      nursing and health sciences research. To date, much of the research has relied on
      traditional analytic methods to identify the disparities and develop clinical
      interventions. However, health disparities are typically embedded in complex,
      cultural and contextual issues. Interventions to improve access, quality and care
      among vulnerable populations need to be developed with these factors in mind.
      This article illustrates the benefits of using Qualitative Description as one
      method for assessing, developing and refining interventions with vulnerable
      populations. Qualitative Description study results have tremendous potential to
      translate directly to pressing health care situations and provide clear
      information about ways to improve care.

PMID- 15988450
TI  - The use of focus group methodology in health disparities research.
AB  - Focus group methodology uses focused interviews to obtain information from
      individuals and interactions among individuals in a small group setting. In this
      article we share the insights we have gained from using focus group methodology
      in work with an under-served population of black menopausal women. This
      methodology holds promise for advancing our understanding of, and ultimately
      eliminating, health disparities. Included is a discussion of planning and
      facilitating the focus group, recruiting group members, collecting and analyzing
      the data and reporting the results. Throughout, we explain how we applied these
      principles and we conclude by sharing lessons learned from our study on menopause
      and midlife experiences in Black women.

PMID- 15988451
TI  - Lessons learned: research with rural Mexican-American women.
AB  - The authors share lessons learned from 5 community-based research studies
      involving rural Mexican-American women. The 10 lessons revolved around
      compensation, confidentiality, recruitment, crossing paths, mailings, locating
      people, participation/attendance, translation, children, and closure. Despite
      their clinical knowledge and previous experiences in service with this
      population, researchers found recruiting and retaining participants and data
      collection far more challenging than expected. This article is significant as it
      illustrates the extensive time, expense, and effort required to conduct research
      with a rural population experiencing health disparities. Recommendations are
      provided to assist in planning and designing community-based and culturally
      sensitive research that has realistic time and budget allowances.

PMID- 15988452
TI  - Strategies for successful conduct of research with low-income African American
      populations.
AB  - Health disparities among racial and ethnic minorities are associated with poor
      health outcomes. African Americans bear a disproportionate amount of the burden
      of health disparities. The elimination of health disparities among the nation's
      racial and ethnic groups requires immediate action that the health care community
      cannot accomplish in isolation. Eliminating health disparities calls for new and
      non-traditional partnerships across diverse sectors of the community that include
      research initiatives using culturally competent and participatory action
      methodologies. While there is much evidence documenting health disparities in
      racial and ethnic groups, there is little evidence of successful interventions
      that address health disparities in African Americans. Furthermore, there is
      little direction for successful strategies for recruiting African Americans for
      participation in health disparities research. This article addresses important
      factors to consider when conducting research with low income African Americans
      based on the authors' research experience in health promotion and cancer
      detection and prevention. Strategies for successful conduct of research with low
      income African American populations are offered.

PMID- 15988454
TI  - Chiron Mentoring Program: leadership opportunity in nursing.

PMID- 15988453
TI  - Advancement of health disparities research: a conceptual approach.
AB  - Although nurse researchers have contributed in significant ways to the body of
      literature on health disparities, a broad framework and approach to health
      disparities is needed if we are to understand the complex interplay of variables
      that contribute to health disparities. This article reports on the work of the
      Center for the Advancement of Health Disparities Research and its development of
      a conceptual framework and method for approaching health disparities research and
      on a sample of nursing research consistent with this framework.

PMID- 15988456
TI  - American Academy of Nursing/American Organization of Nurse Executives Workforce
      Commission Technology-Enhanced Nursing Practice Project.

PMID- 15988458
TI  - Airway management in the obese pediatric patient.

PMID- 15988463
TI  - LifeFlight passes second decade of service.

PMID- 15988464
TI  - Revenue generation through GPS-measured mileage.

PMID- 15988465
TI  - Assessment of air medical coverage using the Atlas and Database of Air Medical
      Services and correlations with reduced highway fatality rates.

PMID- 15988466
TI  - Oxygen conservation during long distance transport of ventilated patients.

PMID- 15988467
TI  - Subchronic rolipram delivery activates hippocampal CREB and arc, enhances
      retention and slows down extinction of conditioned fear.
AB  - Rolipram, a type IV-specific phosphodiesterase inhibitor, is known to improve
      memory under various learning tasks. Moreover, Rolipram treatments have been
      shown to increase expression and phosphorylation of a key factor for hippocampal
      memory consolidation, the cAMP-dependent response element-binding protein, CREB.
      However, the exact correlation between hippocampal CREB phosphorylation and
      memory improvement induced by Rolipram has not yet been determined in a CREB
      dependent type of hippocampal-related learning in normogenic, intact rodents.
      Here, we report that subchronic Rolipram delivery by using osmotic minipumps
      increased the basal rat hippocampal expression and phosphorylation of CREB, as
      well as the expression of the cAMP-dependent, memory-related protein, Arc. In
      parallel, the same treatment improved memory consolidation of conditioned fear.
      Furthermore, the increase of CREB phosphorylation and Arc expression consequent
      to the learning experience was enhanced in Rolipram-treated rats, compared to
      controls. By evaluating the time course of memory extinction over 10 days after
      the initial learning test, we also observed significant slowing down of the
      memory extinction rate in Rolipram-treated rats. This effect could be attributed
      to CREB phosphorylation and memory having been initially higher, as osmotic
      minipumps stopped to release Rolipram the first day after the initial learning
      test. Our data define the conditions through which the pharmacological
      manipulation of hippocampal CREB expression and activation result in memory
      amelioration in normogenic, intact animals. These results are relevant for the
      study of molecular correlates of memory, and may also be important in view of the
      efforts to design new pharmacological treatments, targeting the CREB pathway and
      leading to enhancement of learning and memory, even in the absence of patent
      neuropathology.

PMID- 15988468
TI  - Nalmefene induced elevation in serum prolactin in normal human volunteers:
      partial kappa opioid agonist activity?
AB  - In humans, mu- and kappa-opioid receptor agonists lower tuberoinfundibular
      dopamine, which tonically inhibits prolactin release. Serum prolactin is,
      therefore, a useful biomarker for tuberoinfundibular dopamine. The current study
      evaluated the unexpected finding that the relative mu- and kappa-opioid receptor
      selective antagonist nalmefene increases serum prolactin, indicating possible
      kappa-opioid receptor agonist activity. In all, 33 healthy human volunteers (14
      female) with no history of psychiatric or substance use disorders received
      placebo, nalmefene 3 mg, and nalmefene 10 mg in a double-blind manner. Drugs were
      administered between 0900 and 1000 on separate days via 2-min intravenous
      infusion. Serial blood specimens were analyzed for serum levels of prolactin.
      Additional in vitro studies of nalmefene binding to cloned human kappa-opioid
      receptors transfected into Chinese hamster ovary cells were performed. Compared
      to placebo, both doses of nalmefene caused significant elevations in serum
      prolactin (p<0.002 for nalmefene 3 mg and p<0.0005 for nalmefene 10 mg). There
      was no difference in prolactin response between the 3 and 10 mg doses. Binding
      assays confirmed nalmefene's affinity at kappa-opioid receptors and antagonism of
      mu-opioid receptors. [(35)S]GTPgammaS binding studies demonstrated that nalmefene
      is a full antagonist at mu-opioid receptors and has partial agonist properties at
      kappa-opioid receptors. Elevations in serum prolactin following nalmefene are
      consistent with this partial agonist effect at kappa-opioid receptors. As kappa
      opioid receptor activation can lower dopamine in brain regions important to the
      persistence of alcohol and cocaine dependence, the partial kappa agonist effect
      of nalmefene may enhance its therapeutic efficacy in selected addictive diseases.

PMID- 15988469
TI  - Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic
      response identical to that obtained by complex environment rearing.
AB  - Recent data suggest that Alzheimer's patients who discontinue treatment with
      cholinesterase inhibitors have a significantly delayed cognitive decline as
      compared to patients receiving placebo. Such observations suggest cholinesterase
      inhibitors to provide a disease-modifying effect as well as symptomatic relief
      and, moreover, that this benefit remains after drug withdrawal. Consistent with
      this suggestion, we now demonstrate that chronic administration of tacrine,
      nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the
      basal frequency of dentate polysialylated neurons in a manner similar to the
      enhanced neuroplasticity achieved through complex environment rearing. While both
      drug-treated and complex environment reared animals continue to exhibit memory
      associated activation of hippocampal polysialylated neurons, the magnitude is
      significantly reduced suggesting that such interventions induce a more robust
      memory pathway that can acquire and consolidate new information more efficiently.
      This hypothesis is supported by our findings of improved learning behavior and
      enhanced resistance to cholinergic deficits seen following either intervention.
      Furthermore, the level of enhancement of basal neuroplastic status achieved by
      either drug or environmental intervention correlates directly with improved
      spatial learning ability. As a combination of both interventions failed to
      further increase basal polysialylated cell frequency, complex environment rearing
      and chronic drug regimens most likely enhanced cognitive performance by the same
      mechanism(s). These findings suggest that improved memory-associated synaptic
      plasticity may be the fundamental mechanism underlying the disease modifying
      action of drugs such as cholinesterase inhibitors. Moreover, the molecular and
      cellular events underpinning neuroplastic responses are identified as novel
      targets in the search for interventive drug strategies for the treatment of
      neurodegenerative and neuropsychiatric disorders.

PMID- 15988470
TI  - Association of DNA polymorphisms in the synaptic vesicular amine transporter gene
      (SLC18A2) with alcohol and nicotine dependence.
AB  - The brain synaptic vesicular amine transporter SLCA18A2 is a key component for
      the uptake of monoamines like dopamine or serotonin into vesicles. We have
      analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for
      association with alcohol- and nicotine dependence, using a family-based design.
      Our sample comprised 131 families with alcohol-dependent offspring and 96
      families with at least one nicotine-dependent offspring. For the alcohol
      dependent sample, we found statistical significant association for two single
      markers (rs363387, P=0.03; rs363333, P=0.0066) as well as for several haplotypes
      (minimal P=0.0038). When the sample with alcohol dependence was stratified
      according to gender, we observed increased association for the male subgroup
      (rs363387, P=0.0011). None of the markers showed association in the sample of
      families with nicotine dependence. However, analysis of a combined sample of
      alcohol and nicotine-dependent families resulted in single markers as well as
      several haplotypes showing statistical significant association with substance
      dependence (minimal P=0.0044). We conclude that DNA polymorphisms located in
      SLC18A2 might contribute to the development of substance dependence.

PMID- 15988471
TI  - Hypocretin/orexin selectively increases dopamine efflux within the prefrontal
      cortex: involvement of the ventral tegmental area.
AB  - Hypocretins (HCRTs) modulate a variety of behavioral and physiological processes,
      in part via interactions with multiple ascending modulatory systems. Further,
      HCRT efferents from the lateral hypothalamus innervate midbrain dopamine (DA)
      nuclei, and DA cell bodies express HCRT receptors. Combined, these observations
      suggest that HCRT may influence behavioral state and/or state-dependent processes
      via modulation of DA neurotransmission. The current studies used in vivo
      microdialysis in the unanesthetized rat to first characterize the effect of
      intracerebroventricular infusion of HCRT-1 (0.07, 0.7 nmol) on extracellular
      levels of DA within the prefrontal cortex (PFC) and nucleus accumbens (Acc).
      Electroencephalographic/electromyographic measures of sleep-wake state were
      collected along with select behavioral measures (eg locomotor activity,
      grooming). HCRT-1 dose-dependently increased PFC dialysate DA levels, and these
      increases were closely correlated with increases in time spent awake. In
      contrast, Acc DA levels were unaffected. Additional studies examined whether HCRT
      1 acts directly within the ventral tegmental area (VTA) to selectively increase
      PFC DA efflux and modulate behavioral state. Unilateral infusion of HCRT-1 (0.1,
      1.0 nmol) within the VTA increased PFC, but not Acc, DA levels. Importantly,
      intra-VTA infusion of HCRT-1 increased the time spent awake and grooming.
      Moreover, HCRT-induced increases in both time spent awake and time spent grooming
      were significantly correlated with post-infusion PFC DA levels. The current
      observations predict a prominent modulatory influence of HCRT on PFC-dependent
      cognitive and affective processes that results, in part, from actions within the
      VTA. Additionally, these observations suggest that the activation of VTA DA
      neurons contributes to the behavioral state-modulatory actions of HCRT.

PMID- 15988472
TI  - Genetic inactivation of melanin-concentrating hormone receptor subtype 1 (MCHR1)
      in mice exerts anxiolytic-like behavioral effects.
AB  - The biological effects of the melanin-concentrating hormone (MCH) are mediated by
      the melanin concentrating hormone receptor 1 (MCHR1) in mice. This receptor is
      enriched in brain areas that are involved in the modulation of mood and affect,
      suggesting that MCH-dependent signaling may influence neurobiological mechanisms
      underlying fear and anxiety processes. To test this, we have generated mice
      lacking functional MCHR1 and characterized phenotypic traits using a number of
      behavioral tests. Mice carrying a null mutation of the MCHR1 gene display
      anxiolytic-like behavior across a battery different behavioral paradigms commonly
      used to assess fear and anxiety responses in rodents: open field, elevated plus
      maze, social interaction, and stress-induced hyperthermia. The brain serotonin (5
      HT) system is central to the control of mood- and anxiety-related processes. To
      examine the impact of MCHR1 receptor deletion on 5-HT neurotransmission, we used
      in vivo microdialysis in freely moving knockout and wild-type mice. Baseline
      dialysate 5-HT levels were significantly lower in MCHR1 knockout mice as compared
      with wild-type controls (9.53+/-0.24 fmol for wild types vs 6.91+/-0.36 fmol for
      knockouts) in the prefrontal cortex (PFC), one of the main target structures of
      the serotonergic system and one that is highly associated with the control of
      emotional processes. Moreover, forced swim increased 5-HT efflux in the PFC of
      wild-type but not MCHR1 knockout mice. In summary, we show that MCHR1 can
      modulate stress- and anxiety-like behaviors and suggest that this may be due to
      changes in serotonergic transmission in forebrain regions.

PMID- 15988473
TI  - Aripiprazole attenuates the discriminative-stimulus and subject-rated effects of
      D-amphetamine in humans.
AB  - The results of animal research suggest that the use of partial agonists at
      dopamine (DA) D2 receptors may be an effective strategy for the treatment of
      stimulant dependence. Aripiprazole is an atypical antipsychotic that has partial
      agonist activity at D2 receptors. In this experiment, seven human participants
      with a history of nontherapeutic stimulant use learned to discriminate 15 mg oral
      D-amphetamine. After acquiring the discrimination (ie > or =80% correct
      responding on four consecutive sessions), the effects of a range of doses of D
      amphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with
      aripiprazole (0 and 20 mg), were assessed. D-Amphetamine alone functioned as a
      discriminative stimulus, produced prototypical subject-rated drug effects (eg
      increased ratings of Active, Alert, Energetic) and elevated cardiovascular
      indices. These effects were generally a function of dose. Aripiprazole alone did
      not occasion D-amphetamine-appropriate responding or produce subject-rated
      effects, but modestly impaired performance. Administration of aripiprazole
      significantly attenuated the discriminative-stimulus and cardiovascular effects
      of D-amphetamine, as well as some of the subject-rated drug effects. These data
      are consistent with previous preclinical findings and suggest that DA partial
      agonists deserve further evaluation as potential pharmacotherapies in the
      management of stimulant dependence. Future studies should investigate the ability
      of aripiprazole or related compounds to attenuate the behavioral effects of
      stimulants associated with a greater degree of dependence, such as
      methamphetamine or cocaine, in dependent individuals.

PMID- 15988474
TI  - Cortical white matter microstructural abnormalities in bipolar disorder.
AB  - This article reports on preliminary findings describing microstructural
      abnormalities in the white matter of cortical areas thought to be associated with
      bipolar disorder. In all, 14 patients with bipolar disorder and 21
      nonpsychiatrically ill control subjects underwent MR imaging including a
      diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm(2)/s).
      DTI data were analyzed on a workstation using a program that allowed calculation
      of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the
      following three white matter fiber tracts bilaterally: the orbital frontal
      cortex, and the superior and middle frontal gyri. These values were compared
      across patient groups. The left and right orbital frontal white matter exhibited
      significantly higher ADC values in bipolar subjects than control subjects on both
      the left (p=0.028) and right (p=0.011). Microstructural changes in the white
      matter of the orbital frontal areas as reflected by increased ADC values appear
      to be associated with bipolar disorder. Further research is needed to better
      understand the interaction of microstructural changes and bipolar symptoms and
      whether these changes are specific to bipolar disorder.

PMID- 15988475
TI  - Intersubject variability and reproducibility of 15O PET studies.
AB  - Oxygen-15 positron emission tomography (15O PET) can provide important data
      regarding patients with head injury. We provide reference data on intersubject
      variability and reproducibility of cerebral blood flow (CBF), cerebral blood
      volume (CBV), cerebral metabolism (CMRO2) and oxygen extraction fraction (OEF) in
      patients and healthy controls, and explored alternative ways of assessing
      reproducibility within the context of a single PET study. In addition, we used
      independent measurements of CBF and CMRO2 to investigate the effect of
      mathematical correlation on the relationship between flow and metabolism. In
      patients, intersubject coefficients of variation (CoV) for CBF, CMRO2 and OEF
      were larger than in controls (32.9%+/-2.2%, 23.2%+/-2.0% and 22.5%+/-3.4% versus
      13.5%+/-1.4%, 12.8%+/-1.1% and 7.3%+/-1.2%), while CoV for CBV were lower
      (15.2%+/-2.1% versus 22.5%+/-2.8%) (P<0.001). The CoV for the test-retest
      reproducibility of CBF, CBV, CMRO2 and OEF in patients were 2.1%+/-1.5%, 3.8%+/
      3.0%, 3.7%+/-3.0% and 4.6%+/-3.5%, respectively. These were much lower than the
      intersubject CoV figures, and were similar to alternative measures of
      reproducibility obtained by fractionating data from a single study. The
      physiological relationship between flow and metabolism was preserved even when
      mathematically independent measures were used for analysis. These data provide a
      context for the design and interpretation of interventional PET studies. While
      ideally each centre should develop its own bank of such data, the figures
      provided will allow initial generic approximations of sample size for such
      studies.

PMID- 15988476
TI  - Neurotoxic zinc translocation into hippocampal neurons is inhibited by
      hypothermia and is aggravated by hyperthermia after traumatic brain injury in
      rats.
AB  - Hypothermia reduces excitotoxic neuronal damage after seizures, cerebral ischemia
      and traumatic brain injury (TBI), while hyperthermia exacerbates damage from
      these insults. Presynaptic release of ionic zinc (Zn2+), translocation and
      accumulation of Zn2+ ions in postsynaptic neurons are important mechanisms of
      excitotoxic neuronal injury. We hypothesized that temperature-dependent
      modulation of excitotoxicity is mediated in part by temperature-dependent changes
      in the synaptic release and translocation of Zn2+. In the present studies, we
      used autometallographic (AMG) and fluorescent imaging of N-(6-methoxy-8-quinolyl)
      para-toluenesulfonamide (TSQ) staining to quantify the influence of temperature
      on translocation of Zn2+ into hippocampal neurons in adult rats after weight drop
      induced TBI. The central finding was that TBI-induced Zn2+ translocation is
      strongly influenced by brain temperature. Vesicular Zn2+ release was detected by
      AMG staining 1 h after TBI. At 30 degrees C, hippocampus showed almost no
      evidence of vesicular Zn2+ release from presynaptic terminals; at 36.5 degrees C,
      the hippocampus showed around 20% to 30% presynaptic vesicular Zn2+ release; and
      at 39 degrees C vesicular Zn2+ release was significantly greater (40% to 60%)
      than at 36.5 degrees C. At 6 h after TBI, intracellular Zn2+ accumulation was
      detected by the TSQ staining method, which showed that Zn2+ translocation also
      paralleled the vesicular Zn2+ release. Neuronal injury, assessed by counting
      eosinophilic neurons, also paralleled the translocation of Zn2+, being minimal at
      30 degrees C and maximal at 39 degrees C. We conclude that pathological Zn2+
      translocation in brain after TBI is temperature-dependent and that hypothermic
      neuronal protection might be mediated in part by reduced Zn2+ translocation.

PMID- 15988477
TI  - Temporal profile of T2-weighted MRI distinguishes between pannecrosis and
      selective neuronal death after transient focal cerebral ischemia in the rat.
AB  - Transient middle cerebral artery occlusion (MCAO) by an intraluminal thread leads
      to primarily subcortical infarctions with little sensorimotor impairment in the
      Wistar rat strain. We investigated the course of infarct development in this
      lesion type for 10 weeks using magnetic resonance imaging (MRI) along with
      histological characterization. MCAO was induced in male Wistar rats (260 to 300
      g) for 60 mins. Animals received follow-up T1- and T2-weighted MRI from day 1
      until week 10. Separate groups of animals were analyzed histologically after 2,
      6, and 10 weeks. Histology included immunohistochemistry for neuronal and
      astrocytic markers as well as hematoxylin eosin and luxol fast blue-cresyl violet
      staining. In contrast to lesions involving the cortex, exclusively subcortical
      infarctions were characterized by a complete resolution of initially increased T1
      and T2 relaxation times by 10 weeks. Between 2 and 10 weeks, neuronal death and
      gliosis as well as a dense inflammatory infiltrate were evident in these lesions,
      without damage to fiber tracts or development of cystic cavities. Exclusively
      subcortical lesions in Wistar rats are characterized by normalization of T1 and
      T2 relaxation times, which might, however, not be mistaken for tissue recovery.
      Despite this MRI normalization, selective neuronal death and gliosis develop.
      Although MRI at individual time points might therefore be ambiguous, the temporal
      profile of relaxation time changes over the chronic time period allows
      discrimination of the lesion development into selective neuronal death or
      pannecrosis.

PMID- 15988479
TI  - Sustainable outcomes from Gleneagles.

PMID- 15988478
TI  - A high-resolution map of active promoters in the human genome.
AB  - In eukaryotic cells, transcription of every protein-coding gene begins with the
      assembly of an RNA polymerase II preinitiation complex (PIC) on the promoter. The
      promoters, in conjunction with enhancers, silencers and insulators, define the
      combinatorial codes that specify gene expression patterns. Our ability to analyse
      the control logic encoded in the human genome is currently limited by a lack of
      accurate information regarding the promoters for most genes. Here we describe a
      genome-wide map of active promoters in human fibroblast cells, determined by
      experimentally locating the sites of PIC binding throughout the human genome.
      This map defines 10,567 active promoters corresponding to 6,763 known genes and
      at least 1,196 un-annotated transcriptional units. Features of the map suggest
      extensive use of multiple promoters by the human genes and widespread clustering
      of active promoters in the genome. In addition, examination of the genome-wide
      expression profile reveals four general classes of promoters that define the
      transcriptome of the cell. These results provide a global view of the functional
      relationships among transcriptional machinery, chromatin structure and gene
      expression in human cells.

PMID- 15988480
TI  - Crystal clear.

PMID- 15988481
TI  - Bringing neuroscience to the classroom.

PMID- 15988483
TI  - Clear skies raise global-warming estimates.

PMID- 15988484
TI  - Japan consoled with contracts as France snares fusion project.

PMID- 15988487
TI  - Shrinking budget grounds German space research.

PMID- 15988485
TI  - Japan's university shake-up wins faint praise after first year.

PMID- 15988488
TI  - Science and Africa: a message to the G8 summit.

PMID- 15988490
TI  - Energy: China's burning ambition.

PMID- 15988491
TI  - Educational research: big plans for little brains.

PMID- 15988492
TI  - AIDS vaccine duo.

PMID- 15988493
TI  - Array of possibilities opens up in genotyping.

PMID- 15988494
TI  - Despite some flaws, online submission is the future.

PMID- 15988495
TI  - Thoughtful peer review is worth the time it takes.

PMID- 15988496
TI  - Science and religion can strengthen each other.

PMID- 15988497
TI  - Promoting dialogue is the best way to combat ID in classrooms.

PMID- 15988502
TI  - Now you see it, now you don't.

PMID- 15988503
TI  - Evolutionary biology: males from Mars.

PMID- 15988504
TI  - Fluid dynamics: impact on Everest.

PMID- 15988505
TI  - Cancer biology: summing up cancer stem cells.

PMID- 15988506
TI  - Geophysics: hot fluids and cold crusts.

PMID- 15988507
TI  - Cancer: a changing global view.

PMID- 15988508
TI  - Biophysics: fashionable cells.

PMID- 15988509
TI  - Imaging techniques: particular magnetic insights.

PMID- 15988510
TI  - Gene regulation: expression and silencing coupled.

PMID- 15988512
TI  - Obituary: Keiiti Aki (1930-2005).

PMID- 15988513
TI  - Animal behaviour: continuous activity in cetaceans after birth.
AB  - All mammals previously studied take maximal rest or sleep after birth, with the
      amount gradually decreasing as they grow to adulthood, and adult fruitflies and
      rats die if they are forcibly deprived of sleep. It has therefore been assumed
      that sleep is necessary for development and serves a vital function in adults.
      But we show here that, unlike terrestrial mammals, killer-whale and bottlenose
      dolphin neonates and their mothers show little or no typical sleep behaviour for
      the first postpartum month, avoiding obstacles and remaining mobile for 24 hours
      a day. We find that neonates and their mothers gradually increase the amount of
      time they spend resting to normal adult levels over a period of several months,
      but never exceed these levels. Our findings indicate either that sleep behaviour
      may not have the developmental and life-sustaining functions attributed to it, or
      that alternative mechanisms may have evolved in cetaceans.

PMID- 15988514
TI  - China's environment in a globalizing world.

PMID- 15988515
TI  - Strong present-day aerosol cooling implies a hot future.
AB  - Atmospheric aerosols counteract the warming effects of anthropogenic greenhouse
      gases by an uncertain, but potentially large, amount. This in turn leads to large
      uncertainties in the sensitivity of climate to human perturbations, and therefore
      also in carbon cycle feedbacks and projections of climate change. In the future,
      aerosol cooling is expected to decline relative to greenhouse gas forcing,
      because of the aerosols' much shorter lifetime and the pursuit of a cleaner
      atmosphere. Strong aerosol cooling in the past and present would then imply that
      future global warming may proceed at or even above the upper extreme of the range
      projected by the Intergovernmental Panel on Climate Change.

PMID- 15988516
TI  - Short-lived orogenic cycles and the eclogitization of cold crust by spasmodic hot
      fluids.
AB  - Collision tectonics and the associated transformation of continental crust to
      high-pressure rocks (eclogites) are generally well-understood processes, but
      important contradictions remain between tectonothermal models and petrological
      isotopic data obtained from such rocks. Here we use 40Ar-39Ar data coupled with a
      thermal model to constrain the time-integrated duration of an orogenic cycle (the
      burial and exhumation of a particular segment of the crust) to be less than 13
      Myr. We also determine the total duration of associated metamorphic events to be
      approximately 20 kyr, and of individual heat pulses experienced by the rocks to
      be as short as 10 years. Such short timescales are indicative of rapid tectonic
      processes associated with catastrophic deformation events (earthquakes). Such
      events triggered transient heat advection by hot fluid along deformation (shear)
      zones, which cut relatively cool and dry subducted crust. In contrast to current
      thermal models that assume thermal equilibrium and invoke high ambient
      temperatures in the thickened crust, our non-steady-state cold-crust model
      satisfactorily explains several otherwise contradictory geological observations.

PMID- 15988518
TI  - The U/Th production ratio and the age of the Milky Way from meteorites and
      Galactic halo stars.
AB  - Some heavy elements (with atomic number A > 69) are produced by the 'rapid' (r)
      process of nucleosynthesis, where lighter elements are bombarded with a massive
      flux of neutrons. Although this is characteristic of supernovae and neutron star
      mergers, uncertainties in where the r-process occurs persist because stellar
      models are too crude to allow precise quantification of this phenomenon. As a
      result, there are many uncertainties and assumptions in the models used to
      calculate the production ratios of actinides (like uranium-238 and thorium-232).
      Current estimates of the U/Th production ratio range from approximately 0.4 to
      0.7. Here I show that the U/Th abundance ratio in meteorites can be used, in
      conjunction with observations of low-metallicity stars in the halo of the Milky
      Way, to determine the U/Th production ratio very precisely (0.57(+0.037)(-0.031).
      This value can be used in future studies to constrain the possible nuclear mass
      formulae used in r-process calculations, to help determine the source of Galactic
      cosmic rays, and to date circumstellar grains. I also estimate the age of the
      Milky Way (14.5(+2.8)(-2.2)Gyr in a way that is independent of the uncertainties
      associated with fluctuations in the microwave background or models of stellar
      evolution.

PMID- 15988517
TI  - Structure of a Na+/H+ antiporter and insights into mechanism of action and
      regulation by pH.
AB  - The control by Na+/H+ antiporters of sodium/proton concentration and cell volume
      is crucial for the viability of all cells. Adaptation to high salinity and/or
      extreme pH in plants and bacteria or in human heart muscles requires the action
      of Na+/H+ antiporters. Their activity is tightly controlled by pH. Here we
      present the crystal structure of pH-downregulated NhaA, the main antiporter of
      Escherichia coli and many enterobacteria. A negatively charged ion funnel opens
      to the cytoplasm and ends in the middle of the membrane at the putative ion
      binding site. There, a unique assembly of two pairs of short helices connected by
      crossed, extended chains creates a balanced electrostatic environment. We propose
      that the binding of charged substrates causes an electric imbalance, inducing
      movements, that permit a rapid alternating-access mechanism. This ion-exchange
      machinery is regulated by a conformational change elicited by a pH signal
      perceived at the entry to the cytoplasmic funnel.

PMID- 15988519
TI  - Neutron and X-ray diffraction study of the broken symmetry phase transition in
      solid deuterium.
AB  - The solid hydrogen compounds D2, HD and H2 remain quantum molecular solids up to
      pressures in the 100 GPa range. A remarkable macroscopic consequence is the
      existence of a pressure-induced broken symmetry phase transition, in which the
      molecules go from a spherical rotational state to an anisotropic rotational
      state. Theoretical understanding of the broken symmetry phase structure remains
      controversial, despite numerous studies. Some open questions concern the
      existence of long- or short-range orientational order; whether a strong isotopic
      shift on the transition pressure should be assigned to the nuclear zero-point
      motion or to quantum localization; and whether the structures are cubic,
      hexagonal or orthorhombic. Here we present experimental data on the structure of
      the broken symmetry phase in solid D2, obtained by a combination of neutron and X
      ray diffraction up to 60 GPa. Our data are incompatible with orthorhombic
      structures predicted by recent theoretical works. We find that the broken
      symmetry phase structure is incommensurate with local orientational order, being
      similar to that found in metastable cubic para-D2.

PMID- 15988520
TI  - Soft X-ray microscopy at a spatial resolution better than 15 nm.
AB  - Analytical tools that have spatial resolution at the nanometre scale are
      indispensable for the life and physical sciences. It is desirable that these
      tools also permit elemental and chemical identification on a scale of 10 nm or
      less, with large penetration depths. A variety of techniques in X-ray imaging are
      currently being developed that may provide these combined capabilities. Here we
      report the achievement of sub-15-nm spatial resolution with a soft X-ray
      microscope--and a clear path to below 10 nm--using an overlay technique for zone
      plate fabrication. The microscope covers a spectral range from a photon energy of
      250 eV (approximately 5 nm wavelength) to 1.8 keV (approximately 0.7 nm), so that
      primary K and L atomic resonances of elements such as C, N, O, Al, Ti, Fe, Co and
      Ni can be probed. This X-ray microscopy technique is therefore suitable for a
      wide range of studies: biological imaging in the water window; studies of wet
      environmental samples; studies of magnetic nanostructures with both elemental and
      spin-orbit sensitivity; studies that require viewing through thin windows,
      coatings or substrates (such as buried electronic devices in a silicon chip); and
      three-dimensional imaging of cryogenically fixed biological cells.

PMID- 15988521
TI  - Tomographic imaging using the nonlinear response of magnetic particles.
AB  - The use of contrast agents and tracers in medical imaging has a long history.
      They provide important information for diagnosis and therapy, but for some
      desired applications, a higher resolution is required than can be obtained using
      the currently available medical imaging techniques. Consider, for example, the
      use of magnetic tracers in magnetic resonance imaging: detection thresholds for
      in vitro and in vivo imaging are such that the background signal from the host
      tissue is a crucial limiting factor. A sensitive method for detecting the
      magnetic particles directly is to measure their magnetic fields using
      relaxometry; but this approach has the drawback that the inverse problem
      (associated with transforming the data into a spatial image) is ill posed and
      therefore yields low spatial resolution. Here we present a method for obtaining a
      high-resolution image of such tracers that takes advantage of the nonlinear
      magnetization curve of small magnetic particles. Initial 'phantom' experiments
      are reported that demonstrate the feasibility of the imaging method. The
      resolution that we achieve is already well below 1 mm. We evaluate the prospects
      for further improvement, and show that the method has the potential to be
      developed into an imaging method characterized by both high spatial resolution as
      well as high sensitivity.

PMID- 15988522
TI  - Remobilization of southern African desert dune systems by twenty-first century
      global warming.
AB  - Although desert dunes cover 5 per cent of the global land surface and 30 per cent
      of Africa, the potential impacts of twenty-first century global warming on desert
      dune systems are not well understood. The inactive Sahel and southern African
      dune systems, which developed in multiple arid phases since the last interglacial
      period, are used today by pastoral and agricultural systems that could be
      disrupted if climate change alters twenty-first century dune dynamics. Empirical
      data and model simulations have established that the interplay between dune
      surface erodibility (determined by vegetation cover and moisture availability)
      and atmospheric erosivity (determined by wind energy) is critical for dunefield
      dynamics. This relationship between erodibility and erosivity is susceptible to
      climate-change impacts. Here we use simulations with three global climate models
      and a range of emission scenarios to assess the potential future activity of
      three Kalahari dunefields. We determine monthly values of dune activity by
      modifying and improving an established dune mobility index so that it can account
      for global climate model data outputs. We find that, regardless of the emission
      scenario used, significantly enhanced dune activity is simulated in the southern
      dunefield by 2039, and in the eastern and northern dunefields by 2069. By 2099
      all dunefields are highly dynamic, from northern South Africa to Angola and
      Zambia. Our results suggest that dunefields are likely to be reactivated (the
      sand will become significantly exposed and move) as a consequence of twenty-first
      century climate warming.

PMID- 15988523
TI  - Imaging the Indian subcontinent beneath the Himalaya.
AB  - The rocks of the Indian subcontinent are last seen south of the Ganges before
      they plunge beneath the Himalaya and the Tibetan plateau. They are next glimpsed
      in seismic reflection profiles deep beneath southern Tibet, yet the surface seen
      there has been modified by processes within the Himalaya that have consumed parts
      of the upper Indian crust and converted them into Himalayan rocks. The geometry
      of the partly dismantled Indian plate as it passes through the Himalayan process
      zone has hitherto eluded imaging. Here we report seismic images both of the
      decollement at the base of the Himalaya and of the Moho (the boundary between
      crust and mantle) at the base of the Indian crust. A significant finding is that
      strong seismic anisotropy develops above the decollement in response to shear
      processes that are taken up as slip in great earthquakes at shallower depths.
      North of the Himalaya, the lower Indian crust is characterized by a high-velocity
      region consistent with the formation of eclogite, a high-density material whose
      presence affects the dynamics of the Tibetan plateau.

PMID- 15988524
TI  - Experimental demonstration of chaos in a microbial food web.
AB  - Discovering why natural population densities change over time and vary with
      location is a central goal of ecological and evolutional disciplines. The
      recognition that even simple ecological systems can undergo chaotic behaviour has
      made chaos a topic of considerable interest among theoretical ecologists.
      However, there is still a lack of experimental evidence that chaotic behaviour
      occurs in the real world of coexisting populations in multi-species systems. Here
      we study the dynamics of a defined predator-prey system consisting of a
      bacterivorous ciliate and two bacterial prey species. The bacterial species
      preferred by the ciliate was the superior competitor. Experimental conditions
      were kept constant with continuous cultivation in a one-stage chemostat. We show
      that the dynamic behaviour of such a two-prey, one-predator system includes
      chaotic behaviour, as well as stable limit cycles and coexistence at equilibrium.
      Changes in the population dynamics were triggered by changes in the dilution
      rates of the chemostat. The observed dynamics were verified by estimating the
      corresponding Lyapunov exponents. Such a defined microbial food web offers a new
      possibility for the experimental study of deterministic chaos in real biological
      systems.

PMID- 15988525
TI  - Clonal reproduction by males and females in the little fire ant.
AB  - Sexual reproduction can lead to major conflicts between sexes and within genomes.
      Here we report an extreme case of such conflicts in the little fire ant Wasmannia
      auropunctata. We found that sterile workers are produced by normal sexual
      reproduction, whereas daughter queens are invariably clonally produced. Because
      males usually develop from unfertilized maternal eggs in ants and other
      haplodiploid species, they normally achieve direct fitness only through diploid
      female offspring. Hence, although the clonal production of queens increases the
      queen's relatedness to reproductive daughters, it potentially reduces male
      reproductive success to zero. In an apparent response to this conflict between
      sexes, genetic analyses reveal that males reproduce clonally, most likely by
      eliminating the maternal half of the genome in diploid eggs. As a result, all
      sons have nuclear genomes identical to those of their father. The obligate clonal
      production of males and queens from individuals of the same sex effectively
      results in a complete separation of the male and female gene pools. These
      findings show that the haplodiploid sex-determination system provides grounds for
      the evolution of extraordinary genetic systems and new types of sexual conflict.

PMID- 15988526
TI  - Orofacial somatomotor responses in the macaque monkey homologue of Broca's area.
AB  - In the ventrolateral frontal lobe of the human brain there is a distinct entity,
      cytoarchitectonic area 44 (Broca's area), which is crucial in speech production.
      There has been controversy over whether monkeys possess an area comparable to
      human area 44. We have addressed this question in the macaque monkey by combining
      quantitative architectonic analysis of the cortical areas within the
      ventrolateral frontal region with electrophysiological recording of neuron
      activity and electrical intracortical microstimulation. Here we show that,
      immediately in front of the ventral part of the agranular premotor cortical area
      6, there is a distinct cortical area that is architectonically comparable to
      human area 44 and that this monkey area 44 is involved with the orofacial
      musculature. We suggest that area 44 might have evolved originally as an area
      exercising high-level control over orofacial actions, including those related to
      communicative acts, and that, in the human brain, area 44 eventually also came to
      control certain aspects of the speech act.

PMID- 15988527
TI  - Auxin inhibits endocytosis and promotes its own efflux from cells.
AB  - One of the mechanisms by which signalling molecules regulate cellular behaviour
      is modulating subcellular protein translocation. This mode of regulation is often
      based on specialized vesicle trafficking, termed constitutive cycling, which
      consists of repeated internalization and recycling of proteins to and from the
      plasma membrane. No such mechanism of hormone action has been shown in plants
      although several proteins, including the PIN auxin efflux facilitators, exhibit
      constitutive cycling. Here we show that a major regulator of plant development,
      auxin, inhibits endocytosis. This effect is specific to biologically active
      auxins and requires activity of the Calossin-like protein BIG. By inhibiting the
      internalization step of PIN constitutive cycling, auxin increases levels of PINs
      at the plasma membrane. Concomitantly, auxin promotes its own efflux from cells
      by a vesicle-trafficking-dependent mechanism. Furthermore, asymmetric auxin
      translocation during gravitropism is correlated with decreased PIN
      internalization. Our data imply a previously undescribed mode of plant hormone
      action: by modulating PIN protein trafficking, auxin regulates PIN abundance and
      activity at the cell surface, providing a mechanism for the feedback regulation
      of auxin transport.

PMID- 15988528
TI  - The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C.
      elegans and S. cerevisiae.
AB  - SCF-type E3 ubiquitin ligases are multi-protein complexes required for
      polyubiquitination and subsequent degradation of target proteins by the 26S
      proteasome. Cullins, together with the RING-finger protein Rbx1, form the
      catalytic core of the ligase, and recruit the substrate-recognition module.
      Cycles of covalent modification of cullins by the ubiquitin-like molecule Nedd8
      (neddylation) and removal of Nedd8 by the COP9 signalosome (deneddylation)
      positively regulate E3 ligase activity. Here we report the identification and
      analysis of a widely conserved protein that is required for cullin neddylation in
      the nematode Caenorhabditis elegans and the yeast Saccharomyces cerevisiae. C.
      elegans DCN-1 and S. cerevisiae Dcn1p (defective in cullin neddylation) are
      characterized by a novel UBA-like ubiquitin-binding domain and a DUF298 domain of
      unknown function. Consistent with their requirements for neddylation, DCN-1 and
      Dcn1p directly bind Nedd8 and physically associate with cullins in both species.
      Moreover, overexpression of Dcn1p in yeast results in the accumulation of Nedd8
      modified cullin Cdc53p. Both in vivo and in vitro experiments indicate that Dcn1p
      does not inhibit deneddylation of Cdc53p by the COP9 signalosome, but greatly
      increases the kinetics of the neddylation reaction.

PMID- 15988529
TI  - Global histone modification patterns predict risk of prostate cancer recurrence.
AB  - Aberrations in post-translational modifications of histones have been shown to
      occur in cancer cells but only at individual promoters; they have not been
      related to clinical outcome. Other than being targeted to promoters,
      modifications of histones, such as acetylation and methylation of lysine and
      arginine residues, also occur over large regions of chromatin including coding
      regions and non-promoter sequences, which are referred to as global histone
      modifications. Here we show that changes in global levels of individual histone
      modifications are also associated with cancer and that these changes are
      predictive of clinical outcome. Through immunohistochemical staining of primary
      prostatectomy tissue samples, we determined the percentage of cells that stained
      for the histone acetylation and dimethylation of five residues in histones H3 and
      H4. Grouping of samples with similar patterns of modifications identified two
      disease subtypes with distinct risks of tumour recurrence in patients with low
      grade prostate cancer. These histone modification patterns were predictors of
      outcome independently of tumour stage, preoperative prostate-specific antigen
      levels, and capsule invasion. Thus, widespread changes in specific histone
      modifications indicate previously undescribed molecular heterogeneity in prostate
      cancer and might underlie the broad range of clinical behaviour in cancer
      patients.

PMID- 15988530
TI  - Dynamics of chronic myeloid leukaemia.
AB  - The clinical success of the ABL tyrosine kinase inhibitor imatinib in chronic
      myeloid leukaemia (CML) serves as a model for molecularly targeted therapy of
      cancer, but at least two critical questions remain. Can imatinib eradicate
      leukaemic stem cells? What are the dynamics of relapse due to imatinib
      resistance, which is caused by mutations in the ABL kinase domain? The precise
      understanding of how imatinib exerts its therapeutic effect in CML and the
      ability to measure disease burden by quantitative polymerase chain reaction
      provide an opportunity to develop a mathematical approach. We find that a four
      compartment model, based on the known biology of haematopoietic differentiation,
      can explain the kinetics of the molecular response to imatinib in a 169-patient
      data set. Successful therapy leads to a biphasic exponential decline of leukaemic
      cells. The first slope of 0.05 per day represents the turnover rate of
      differentiated leukaemic cells, while the second slope of 0.008 per day
      represents the turnover rate of leukaemic progenitors. The model suggests that
      imatinib is a potent inhibitor of the production of differentiated leukaemic
      cells, but does not deplete leukaemic stem cells. We calculate the probability of
      developing imatinib resistance mutations and estimate the time until detection of
      resistance. Our model provides the first quantitative insights into the in vivo
      kinetics of a human cancer.

PMID- 15988531
TI  - Escherichia coli swim on the right-hand side.
AB  - The motion of peritrichously flagellated bacteria close to surfaces is relevant
      to understanding the early stages of biofilm formation and of pathogenic
      infection. This motion differs from the random-walk trajectories of cells in free
      solution. Individual Escherichia coli cells swim in clockwise, circular
      trajectories near planar glass surfaces. On a semi-solid agar substrate, cells
      differentiate into an elongated, hyperflagellated phenotype and migrate
      cooperatively over the surface, a phenomenon called swarming. We have developed a
      technique for observing isolated E. coli swarmer cells moving on an agar
      substrate and confined in shallow, oxidized poly(dimethylsiloxane) (PDMS)
      microchannels. Here we show that cells in these microchannels preferentially
      'drive on the right', swimming preferentially along the right wall of the
      microchannel (viewed from behind the moving cell, with the agar on the bottom).
      We propose that when cells are confined between two interfaces--one an agar gel
      and the second PDMS--they swim closer to the agar surface than to the PDMS
      surface (and for much longer periods of time), leading to the preferential
      movement on the right of the microchannel. Thus, the choice of materials guides
      the motion of cells in microchannels.

PMID- 15988535
TI  - NRAMP1 is not associated with asthma, atopy, and serum immunoglobulin E levels in
      the French Canadian population.
AB  - Reduced infection by mycobacteria, including Mycobacterium tuberculosis, may be
      partly responsible for increased prevalence of allergic and autoimmune diseases
      in developed countries. In a murine model of innate resistance to mycobacteria,
      the Nramp1 gene has been shown to affect asthma susceptibility. From this
      observation, it was proposed that human NRAMP1 may be a modulator of asthma risk
      in human populations. To experimentally test the candidacy of NRAMP1 in asthma
      susceptibility, we characterized five genetic variants of NRAMP1 (5'CAn, 274C>T,
      469+14G>C, D543N, and 1729+del4) in an asthma family-based cohort from
      northeastern Quebec. We did not observe any significant association between
      NRAMP1 variants (either allele or haplotype specific) with asthma, atopy, or
      serum immunoglobulin E levels. These results demonstrate that, in spite of direct
      involvement of Nramp1 in a murine asthma model, in human populations NRAMP1 is
      not likely to be a major contributor to the genetic etiology of asthma and asthma
      related phenotypes.

PMID- 15988536
TI  - Gender-related differences in left ventricular structural and functional
      responses to hypertension.

PMID- 15988537
TI  - Is there an association between hypertension and the development of coronary
      collateral flow?

PMID- 15988538
TI  - US demographic trends in mid-arm circumference and recommended blood pressure
      cuffs: 1988-2002.
AB  - Mid-arm circumference (AC) measurement is a prerequisite for the selection of
      properly sized blood pressure (BP) cuffs and accurate BP readings. This study
      examined trends in the frequency distribution of mid-AC and corresponding
      recommended BP cuff sizes using National Health and Nutrition Examination Survey
      (NHANES) III (1988-1994) and NHANES 1999-2002 data. Both surveys used a complex
      sample design to obtain nationally representative samples of the civilian
      noninstitutionalized US population. The sample consisted of 7453 men and 8372
      women from NHANES III and 4295 men and 4838 women from NHANES 1999-2002. Mean mid
      AC (cm) and associated American Heart Association-defined cuff sizes were
      assessed. Variables were analysed by gender, age, race/ethnicity, and by
      hypertension or diabetic co-morbidity. Mid-AC increased significantly between
      surveys for all age groups; the greatest increase in mid-AC occurred in the 20-39
      year age group. Data from NHANES 1992-2002 show that among nonHispanic white and
      nonHispanic black men aged 20-59 years, the mean mid-AC was >34 cm. Among NHB
      women aged 40 years and above, the mean mid-AC was greater than or equal to 34
      cm. In all, 42% of all men and 26% of all women aged 40-59 years required large
      BP cuffs. In all, 39% of individuals classified as hypertensive and 47% of self
      reported diabetics required a BP cuff greater than the standard adult size. In
      conclusion, mean mid-AC has increased across many demographic subgroups in the US
      with implications for the accuracy of BP measurement in clinical practice.

PMID- 15988539
TI  - Geographical difference in the prevalence of isolated systolic hypertension in
      middle-aged men and women in Korea: the Korean Health and Genome Study.
AB  - To compare geographical difference in the prevalence of isolated systolic
      hypertension (ISH) in between urban (Ansan) and rural (Ansung) Korean adults aged
      40-69 years, 4351 men and 4604 women enrolled in the Korean Health and Genome
      Study were analysed. Information was collected regarding gender, alcohol intake,
      smoking status, household income, occupation, and years of education by trained
      interviewers. Eligible subjects included untreated hypertensive and normotensive
      subjects. ISH was defined as a systolic blood pressure (SBP) > or = 140 mmHg and
      diastolic BP <90 mmHg. The overall age-adjusted prevalence of ISH was 4.1%. The
      prevalence of ISH in Ansung (5.7%) was higher than in Ansan (2.5%, P < 0.05).
      Also it increased with increments of age, from 1.0 to 12.8% in Ansung (P < 0.05)
      and from 0.3 to 13.0% in Ansan (P < 0.05). In those with body mass index (BMI) >
      or = 30.0 kg/m2 in Ansung, the prevalence of ISH in women was twice as much as in
      men. The prevalence of ISH in obese men and women with a waist-hip ratio > or
      =1.0 and > or = 0.85, respectively, was more than that of nonobese men and women
      in both areas. In Korea, because of industrialization, the age distribution was
      skewed and the Korean population in rural areas is more aged. ISH will become a
      truly major health problem in rural area, because ISH is related to age, BMI and
      waist-hip ratio. Therefore, the Korean government will be required to institute
      different policies in the hypertension management to target populations in rural
      and urban areas.

PMID- 15988540
TI  - Detection and treatment of hypertension in general health-care practice: a
      patient-based study.
AB  - The aim of this study was to describe the pattern of blood pressure (BP)
      distribution in a multiethnic primary care practice in relation to
      sociodemographic characteristics, lifestyle and risk factors. Another aim was to
      analyse the quality of diagnosis and effectiveness of hypertension (HT)
      treatment. In all, 470 adult patients (> or =16 years old) who visited the
      Jordbro Health Centre (JHC), Haninge Municipality, participated in this study. A
      general questionnaire with questions about sociodemographic characteristics,
      lifestyle, health status and chronic disease was used. Medical records:
      information on consultations with the general practitioner and prescriptions were
      collected from the medical records for the year 2001. Furthermore, a medical
      examination was performed: this consisted of weight, height, systolic (SBP) and
      diastolic (DBP) blood pressure, and laboratory analyses including fasting blood
      glucose, serum cholesterol, serum triglycerides, electrocardiogram and
      spirometry. Out of 464 patients, 114 (24.6%) reported HT. Among the HT patients,
      93 (81.6%) had SBP > or =140 mmHg and 52 (45.6%) DBP > or =90 mmHg. Among the
      nonhypertensive patients (n=350), 120 (34.3%) had SBP > or =140 mmHg and 50
      (14.3%) DBP > or =90 mmHg. Furthermore, there are some patients with high BP who
      are unknown or undetected. HT treatment among this population is unsatisfactory
      and greater efforts are required to identify people with high BP and to ensure
      that they are managed according to the best available evidence.

PMID- 15988541
TI  - Association between carotid haemodynamics and inflammation in patients with
      essential hypertension.
AB  - Previous studies have shown that high blood pressure causes chronic inflammation.
      Hypertensive patients are reported to have high-circulating levels of
      proinflammatory cytokines such as interleukin-6 (IL-6) and high sensitive C
      reactive protein (hs-CRP). The pulsatility index (PI) and resistive index (RI)
      are used as markers of peripheral vascular resistance. In the present study, we
      evaluated the relationship between carotid haemodynamics and the proinflammatory
      cytokines, IL-6 and hs-CRP. In all, 41 patients with essential hypertension
      participated. The intima-media thickness (IMT), peak systolic velocity (pVs),
      peak diastolic velocity (pVd) and mean velocity (mV) in the common carotid artery
      were measured using ultrasound Doppler flow methods, and PI [(pVs-pVd)/mV] and RI
      [(pVs-pVd)/pVs] were calculated. Serum IL-6 and hs-CRP concentrations were
      measured by an enzyme-linked immunosorbent assay. IMT was positively correlated
      with age and pulse pressure. Both PI and RI were positively correlated with pulse
      pressure, IL-6 and hs-CRP. A multiple regression analysis revealed that PI and RI
      were independently associated with hs-CRP. These results suggested that carotid
      haemodynamic parameters such as PI and RI are associated with atherosclerosis and
      inflammation in hypertensive patients.

PMID- 15988542
TI  - The prevalence of male sexual dysfunction and potential risk factors in Turkish
      men: a Web-based survey.
AB  - The purpose of this study is to detect the prevalence of sexual dysfunction and
      also to investigate possible risk factors that may cause sexual dysfunction in
      Turkish men. We developed a Web-based survey. In total, 3185 invitations to
      complete the survey were e-mailed and 2288 individuals submitted responses (72%).
      The men were interviewed in person, using the Florida Sexual History
      Questionnaire (FSHQ) Turkish version, and sexual dysfunction was assessed by this
      questionnaire. male sexual dysfunction (MSD) was evaluated with FSHQ. According
      to the FSHQ Turkish version, sexual function domains included sexual desire,
      sexual development, intercourse, erection, ejaculation, and satisfaction.
      According to the FSHQ score, 43.3% reported on MSD (FSHQ score<or=95). The
      prevalence of MSD was 56% in the ages of 15-24 y, 35% in 25-34 y, 26% in 35-44 y,
      40% in the ages of 45-54 y, and 72% in the ages of 55-60 y. MSD was detected as a
      desire problem in 7.3%, sexual development problem in 54.7%, intercourse problem
      in 50.3%, arousal/erectile problem in 59.7%, orgasm/ejaculation problem in 52.7%,
      and satisfaction problem in 59.7%. The age-adjusted risk of developing MSD was
      higher for men with smoking, lower education, and chronic medical diseases. In
      conclusion, the prevalence of MSD is 43.3% in Turkish men. The most important
      risk factor for MSD is smoking. In addition, the presence of younger and older
      age, chronic medical diseases, and lower educational level are important risk
      factors that may cause MSD.

PMID- 15988543
TI  - What is sexual medicine?
AB  - Sexual medicine is unique in that it permeates throughout various medical
      specialties, without having its own defined borders. Urology, gynecology, primary
      care, endocrinology and cardiology are connected to sexual medicine to varying
      degrees. Should sexual medicine be a requisite part of the aforementioned
      teaching programs? Dr Martin Resnick, Lester Persky Professor and Chairman,
      Department of Urology, Case Western Reserve University, provides a perspective on
      this topic.

PMID- 15988544
TI  - Multi-institutional outcome study on the efficacy of closed-suction drainage of
      the scrotum in three-piece inflatable penile prosthesis surgery.
AB  - Infection is a devastating complication of penile prosthesis surgery that occurs
      in approximately 2-5% of all primary inflatable penile primary implants in most
      series. Prevention of hematoma and swelling with closed-suction drains has been
      shown not to increase infection rate and yield an earlier recovery time. Despite
      the intuitive advantages of short-term closed-suction drainage in reducing the
      incidence of postoperative scrotal swelling and associated adverse effects, many
      urologists are reluctant to drain the scrotum because of a theoretical risk of
      introducing an infection. In conclusion, this study was undertaken to evaluate
      the incidence of infection in three-piece penile prosthesis surgery with scrotal
      closed-suction drainage. A retrospective review of 425 consecutive primary three
      piece penile prosthesis implantations was performed at three institutions in New
      Jersey, Ohio, and Arkansas from 1998 to 2002. Following the prosthesis insertion,
      10 French Round Blake (Johnson & Johnson) or, in a few cases, 10 French Jackson
      Pratt, closed-suction drains were placed in each patient for less than 24 h. All
      subjects received standard perioperative antibiotic coverage. Average age at
      implant was 62 y (range 24-92 y). Operative time (incision to skin closure) was
      less than 60 min in the vast majority of cases. There were a total of 14 (3.3%)
      infections and three hematomas (0.7%) during an average 18-month follow-up
      period. In conclusion, this investigation revealed that closed-suction drainage
      of the scrotum for approximately 12-24 h following three-piece inflatable penile
      prosthesis surgery does not result in increased infection rate and is associated
      with a very low incidence of postoperative hematoma formation, swelling, and
      ecchymosis.

PMID- 15988545
TI  - Sexual dysfunction after pelvic surgery.
AB  - Pelvic surgeries are among the most common causes of organic sexual dysfunction
      in men and women. The impact of nerve-sparing surgery on potency has been well
      documented in radical prostatectomy. However, its impact on potency needs to be
      evaluated in other pelvic surgeries. Sexual dysfunction is highly prevalent even
      after multiple technical advances in the field of oncological surgeries. The
      prevalence varies from 8 to 82%, depending on the type of pelvic surgery. In
      females, sexual dysfunction has not been evaluated adequately using validated
      questionnaires. However, in subspecialized circles, treatment for female sexual
      dysfunction is becoming routine. Currently, physicians have several options for
      the treatment of erectile dysfunction (ED) in men. Since the introduction of oral
      PDE-5 inhibitors, oral therapy has become the first-line treatment option for ED,
      irrespective of etiology. Currently available treatment options for the female
      sexual dysfunction include estrogens, androgens, phosphodiesterase inhibitors,
      and dopamine receptor antagonists. Initial reports regarding the role of early
      rehabilitation are encouraging and may become the part of routine practice in the
      management of ED after pelvic surgery. In this article, we summarize the sexual
      dysfunction following pelvic surgeries and their management.

PMID- 15988546
TI  - The relationship between lipid profile and erectile dysfunction.
AB  - The objective of this study is to investigate the relation between serum lipids
      (cholesterol, LDL, HDL, triglyceride (TG)) and erectile dysfunction (ED). The
      experimental methods involved comparison of 100 patients with organic ED (mean
      age of 43.59+/-10.51 y), with 100 healthy individuals (mean age of 43.72+/-9.76
      y) regarding their lipid profile from January 2000 to June 2003 (cholesterol, TG,
      HDL, LDL). The results showed that there was a significant difference between
      mean plasma cholesterol and LDL levels in the individuals suffering from ED and
      the control group (P=0.04 and 0.02, respectively). The TG and HDL mean plasma
      level differences were not significant (P=0.583 and 0.299, respectively). Odds
      ratios for high plasma cholesterol level (>240 mg/dl) and high plasma LDL level
      (>160 mg/dl) were 1.74 and 1.97. The R2 was 0.04 for both cholesterol and LDL.
      Applying linear regression, the coefficient for cholesterol and LDL reduced the
      International Index of Erectile Function questionnaire scores by -0.036 and 
      0.035. In conclusion, this study, the correlation of cholesterol and LDL levels
      with ED strongly supports the role of hyperlipidemia treatment in both the
      prevention and management of ED.

PMID- 15988547
TI  - Using a three-dimension head mounted displayer in audio-visual sexual stimulation
      aids in differential diagnosis of psychogenic from organic erectile dysfunction.
AB  - We designed this study to compare the efficacy of using a three-dimension head
      mounted displayer (3-D HMD) and a conventional monitor in audio-visual sexual
      stimulation (AVSS) in differential diagnosis of psychogenic from organic erectile
      dysfunction (ED). Three groups of subjects such as psychogenic ED, organic ED,
      and healthy control received the evaluation. The change of penile tumescence in
      AVSS was monitored with Nocturnal Electrobioimpedance Volumetric Assessment and
      sexual arousal after AVSS was assessed by a simple question as being good, fair,
      or poor. Both the group of healthy control and psychogenic ED demonstrated a
      significantly higher rate of normal response in penile tumescence (P<0.05) and a
      significantly higher level of sexual arousal (P<0.05) if stimulated with 3-D HMD
      than conventional monitor. In the group of organic ED, even using 3-D HMD in AVSS
      could not give rise to a better response in both assessments. Therefore, we
      conclude that using a 3-D HMD in AVSS helps more to differentiate psychogenic
      from organic ED than a conventional monitor in AVSS.

PMID- 15988548
TI  - Cutaneous effects of smoking.
AB  - BACKGROUND: Cigarette smoking is the single biggest preventable cause of death
      and disability in developed countries and is a significant public health concern.
      While known to be strongly associated with a number of cardiovascular and
      pulmonary diseases and cancers, smoking also leads to a variety of cutaneous
      manifestations. OBJECTIVE: This article reviews the effects of cigarette smoking
      on the skin and its appendages. METHODS: A literature review was based on a
      MEDLINE search (1966-2004) for English-language articles using the MeSH terms
      cutaneous, dermatology, tobacco, skin, and smoking. An additional search was
      subsequently undertaken for articles related to smoking and associated
      mucocutanous diseases, with the focus on pathogenesis and epidemiologic data.
      Articles presenting the highest level of evidence and latest reports were
      preferentially selected. RESULTS: Smoking is strongly associated with numerous
      dermatologic conditions including poor wound healing, wrinkling and premature
      skin aging, squamous cell carcinoma, psoriasis, hidradenitis suppurativa, hair
      loss, oral cancers, and other oral conditions. In addition, it has an impact on
      the skin lesions observed in diabetes, lupus, and AIDS. The evidence linking
      smoking and melanoma, eczema, and acne is inconclusive. Anecdotal data exist on
      the possible protective effects of smoking in oral/genital aphthosis of Behcet's
      disease, herpes labialis, pyoderma gangrenosum, acral melanoma, and Kaposi's
      sarcoma in AIDS patients. CONCLUSIONS: An appreciation of the adverse cutaneous
      consequences of smoking is important. Dermatologists can play an integral role in
      promoting smoking cessation by providing expert opinion and educating the public
      on the deleterious effects of smoking on the skin.

PMID- 15988549
TI  - The frequent use of oral retinoids in combination with other treatments for
      psoriasis: a retrospective analysis.
AB  - BACKGROUND: Combination treatment in psoriasis may be common, logical, and
      appropriate, even if not well tested or well documented by clinical trials. While
      oral retinoids such as acitretin can be used as monotherapy, efficacy can be
      further augmented by combination use with other agents. Similarly, because of its
      safety profile, acitretin can be added in low doses to help patients who have not
      achieved adequate control with other psoriasis treatments. OBJECTIVE: The purpose
      of this study was to assess how oral retinoids are used in combination with other
      drugs to treat psoriasis. METHODS: We assessed the use of acitretin and other
      oral retinoids for the treatment of psoriasis using two sources of information:
      nationally representative survey data from the National Ambulatory Medical Care
      Survey (NAMCS) and local data obtained by chart review of 518 patients seen in a
      university dermatology clinic. RESULTS: In the NAMCS, oral retinoids were
      prescribed with other psoriasis medications at 71% of visits. In the chart
      review, combination use was even more frequent (96% of subjects were on
      combination treatment) and included combinations of acitretin with topicals,
      phototherapy, and other systemic treatments. Adverse events were reported in 53%
      of patients treated with acitretin, although none were severe. CONCLUSION: Use of
      acitretin in combination with many other psoriasis treatments is a common
      practice. Mucocutaneous side effects of oral retinoids are common but with
      appropriate dosing are generally mild.

PMID- 15988550
TI  - Photosensitivity to exogenous agents.
AB  - OBJECTIVE: To better understand cutaneous photosensitivity reactions, a review of
      its etiologic factors, clinical characteristics, pathogenesis, and treatment
      modalities was undertaken. METHODS: Articles discussing the above aspects of
      phototoxic and photoallergic reactions were used to demonstrate what is currently
      known about photoinduced reactions and how to treat them. RESULTS: Upon
      interaction of solar UV radiation with the chemical that is present in
      significant levels on the skin, one of two known reactions may occur in
      susceptible patients: a phototoxicity and/or photoallergy. Phototoxic and
      photoallergic reactions can be diagnosed separately on the basis of pathogenesis,
      clinical characteristics, and histology. Examples of drugs capable of inducing a
      phototoxic reaction include amiodarone, retinoids, nonsteroidal antiinflammatory
      agents, diuretics, and antibiotics. Substances known to cause a photoallergic
      response are fragrances, sunscreens, topical antimicrobials, NSAID, and
      psychiatric medications, such as chlorpromezine. CONCLUSION: Photoinduced
      reactions produced by exogenous chemicals are common skin disorders. Definitive
      therapy requires identifying and removing the offending agent, either the
      photosensitizing chemical or light. The use of fully protective clothing and a
      sunscreen of high SPF are important measures when light exposure is inevitable.

PMID- 15988551
TI  - Metastatic zosteriform squamous cell carcinoma in an immunocompetent patient.
AB  - BACKGROUND: Although described in several reports of internal malignancies
      metastasizing to the skin, zosteriform metastases have been reported in only two
      cases of cutaneous squamous cell carcinoma (SCC). In both of these reports, the
      patients were immunosuppressed related to renal transplantation. OBJECTIVE: We
      present a case of an immunocompetent patient with zosteriform metastases
      originating from a recurrent cutaneous SCC. The lesions were present along the
      maxillary division of the trigeminal nerve. METHODS: Biopsies from eight lesions
      were studied using hematoxylin and eosin (H&E) and with immunohistochemistry.
      RESULTS: Neural involvement was detected in H&E preparations before and during
      excision of the metastatic nodules by Mohs micrographic surgery. The tumor cells
      reacted with antikeratin antibodies. The patient has had no evidence of
      recurrence or metastases 30 months following surgery. CONCLUSION: To our
      knowledge, this is the first case of cutaneous SCC with zosteriform metastases in
      a patient with an intact immune system. SCC should be included in the
      differential diagnosis of lesions presenting in a dermatomal distribution.

PMID- 15988552
TI  - Kikuchi-Fujimoto's necrotizing lymphadenitis in association with discoid lupus
      erthematosus: a case report.
AB  - BACKGROUND: Kikuchi-Fujimoto's necrotizing lymphadenitis (KFNL) is a rare,
      benign, self-limited condition characterized by constitutional symptoms,
      lymphadenopathy, and skin lesions. OBJECTIVE: We report a case of KFNL in a 43
      year-old East Indian woman with a ten-year history of discoid lupus erythematosus
      (DLE) of the scalp and a three-month history of a erythematous plaque on the left
      nasal bridge, cervical lymphadenopathy, and fever. Skin biopsy samples were taken
      from the face and lymph node. RESULTS: Histopathological examination of the skin
      revealed a mixed infiltrate of inflammatory cells, nuclear dust, and histiocytes
      phagocytosing nuclear debris in the reticular dermis. The lymph node showed
      interfollicular liquefactive necrosis, immunoblasts, and a similar cellular
      infiltrate as the skin. The non-necrotic areas demonstrated follicular
      hyperplasia. These pathological changes are associated with a diagnosis of KFNL.
      CONCLUSIONS: KFNL is reported in association with systemic lupus erythematosus,
      but only two other cases of systemic KFNL in association with DLE exist in the
      literature. This case is unique in that the patient presented with cutaneous and
      systemic KFNL in the setting of longstanding DLE.

PMID- 15988553
TI  - An unusual cause of refractive chronic bilateral leg ulceration.
AB  - BACKGROUND: Ulceration of the lower extremities is a common disorder that can be
      very painful. It occurs most frequently in the elderly population as a result of
      venous hypertension. We report an unusual case of a 32-year-old man with an 11
      year history of extensive, painful, bilateral leg ulcers resistant to
      conventional treatment necessitating above-knee amputation of the left leg.
      Eventually, the patient was treated with prednisone, which led to almost complete
      healing of the ulcers of the right leg. OBJECTIVE: The objective of this report
      is to discuss a rare cause of chronic bilateral leg ulceration. METHODS: Detailed
      histopathologic examination showed a complex pattern of overlapping features of
      several specific dermatologic conditions, including necrobiosis lipoidica (NL),
      necrobiotic xanthogranuloma (NXG), and the destructive form of granuloma annulare
      (GA). CONCLUSION: The characteristics of our patient suggest a variant of a
      cutaneous necrobiotic disorder that has not been previously reported. When
      clinicians are confronted with recalcitrant ulcerations in the lower extremity,
      this group of disorders should be considered in the differential diagnosis.

PMID- 15988554
TI  - Cost effectiveness of Elidel in the management of patients with atopic dermatitis
      in Canada.
AB  - BACKGROUND: With increasing pressure on health care resources, it is necessary to
      demonstrate that new treatments are both effective and cost effective. OBJECTIVE:
      The purpose of this study was to assess the cost effectiveness of pimecrolimus
      (Elidel) compared to usual therapy in the treatment of both adults and children
      with atopic eczema in Canada. METHODS: Analysis was performed using a decision
      model which estimated the incremental cost per quality adjusted life year (QALY)
      gained from both a societal and health care perspective. RESULTS: For children,
      Elidel leads an incremental cost per QALY of 38,000 dollars from a societal
      perspective. For adults, the incremental cost per QALY was 35,000 dollars.
      CONCLUSION: Elidel will lead to an overall increase in costs but with an
      improvement in clinical outcomes. The cost effectiveness ratios for Elidel were
      consistently below 50,000 dollars per QALY gained. Given previous funding
      decisions in Canada, Elidel may be considered a cost-effective use of health care
      resources.

PMID- 15988556
TI  - Decreased bone mineral density in patients with neurofibromatosis 1.
AB  - Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases.
      Although there is a considerable variability in clinical expression, NF1 is
      almost fully penetrant in adult patients and may be associated with a variety of
      skeletal anomalies. Spinal deformities are the most common skeletal
      manifestation, with an incidence estimated from 10-25% in various studies. Some
      NF1 patients have a dystrophic form of scoliosis, which is characterized by early
      age at onset and rapid progression. Complications have been reported during
      spinal instrumentation of dystrophic curves due to soft, non-resistant vertebral
      bony tissue, suggesting that an alteration of bone quality may occur in NF1
      patients. Recent studies have suggested that decreased bone mineral density (BMD)
      may occur among patients with NF1. We performed a cross-sectional study on 104
      adults with NF1, using quantitative ultrasonometry (QUS) to investigate whether
      decreased BMD is a general phenomenon in NF1 patients. The data reveal that BMD,
      as measured by age- and gender- adjusted Z-scores, is significantly lower in NF1
      patients than in the normal reference population. The decrease in BMD appears to
      be even more marked among NF1 patients with scoliosis that requires surgical
      treatment. The findings indicate that NF1 produces a generalized alteration of
      bone in addition to the focal osseous dysplasias of the vertebrae, tibia, and
      sphenoid wing that characterize this condition. The pathological mechanism
      underlying these bony changes remains to be elucidated.

PMID- 15988557
TI  - Eosinophilic fasciitis associated with autoimmune phenomena after bone marrow
      transplantation: report of two cases.
AB  - Between January 1992 and May 2004, 189 patients underwent allogeneic bone marrow
      transplantation (BMT) for haematological malignancies from HLA-identical sibling
      donors in our transplantation unit. Of the 189 patients, 2 developed eosinophilic
      fasciitis (EF). The first patient developed Hashimoto's thyroiditis and EF 11 and
      21 months after BMT, respectively. In the second patient EF occurred 9 months
      after BMT, accompanied by antinuclear antibodies, antiextractable nuclear
      antigens and antigliadin antibodies. Both patients were treated with
      extracorporeal photochemotherapy (ECP), resulting in improvement of fasciitis in
      both and normalization of antithyroid antibodies in the first patient. Our data
      confirm the rarity of fasciitis after BMT and the efficacy of ECP, recently
      applied experimentally in one patient for the treatment of fasciitis after BMT.
      Moreover, we report for the first time the association of fasciitis with
      autoimmune phenomena after BMT. The correlation between the two entities is
      supported by remission of Hashimoto's thyroiditis after ECP treatment for
      fasciitis.

PMID- 15988558
TI  - Vasculitic complications of interferon-alpha treatment for chronic hepatitis C
      virus infection: case report and review of the literature.
AB  - Chronic infection with hepatitis C virus (HCV) may be complicated by the
      development of systemic vasculitis. Vasculitis is either caused by mixed
      cryoglobulinemia or a non-cryoglobulinemic vasculitis resembling polyarteritis
      nodosa (PAN). Antiviral treatment with interferon-alpha (IFN) and subsequent
      clearing of HCV mostly leads to improvement of vasculitic symptoms, but
      vasculitis may also be exacerbated and even cases of new onset of vasculitis may
      occur. Exacerbations of both cryoglobulinemic and PAN-type vasculitis in chronic
      HCV infection have been described under treatment with IFN. The most common
      symptom is vasculitic neuropathy. However, peripheral neuropathy in a HCV
      infected patient treated with IFN may also be caused by direct neurotoxic or
      antiangiogenic effects of IFN itself, often requiring a nerve biopsy to establish
      the exact diagnosis. The clinical course of vasculitic complications of IFN
      treatment is variable and ranges from regression of symptoms despite continuation
      of IFN treatment to fatal exacerbations despite termination of IFN treatment and
      additional immunosuppressive therapy. In most cases of IFN-induced vasculitis,
      immunosuppressive therapy with corticosteroids has been employed, leading to
      improvement of symptoms. We report the case of a patient with chronic HCV
      infection who first developed cryoglobulinemic vasculitis after initiation of
      therapy with the polyethylene glycol (PEG)-conjugated form of IFN (PEG-IFN) and
      discuss it in the context of the relevant literature. First onset of
      cryoglobulinemic vasculitis after initiation of IFN therapy has not been
      described so far.

PMID- 15988559
TI  - AINTEGUMENTA-like (AIL) genes are expressed in young tissues and may specify
      meristematic or division-competent states.
AB  - Although several members of the AP2/ERF family of transcription factors are
      important developmental regulators in plants, many genes in this large protein
      family remain uncharacterized. Here, we present a phylogenetic analysis of the 18
      genes that make up the AP2 subgroup of this family. We report expression analyses
      of seven Arabidopsis genes most closely related to the floral development gene
      AINTEGUMENTA (ANT) and show that all AINTEGUMENTA-like (AIL) genes are
      transcribed in multiple tissues during development. They are expressed primarily
      in young actively dividing tissues of a plant and not in mature leaves or stems.
      The spatial distribution of AIL5, AIL6, and AIL7 mRNA in inflorescences was
      characterized by in situ hybridization. Each of these genes is expressed in a
      spatially and temporally distinct pattern within inflorescence meristems and
      flowers. Ectopic expression of AIL5 resulted in a larger floral organ phenotype,
      similar to that resulting from ectopic expression of ANT. Our results are
      consistent with AIL genes having roles in specification of meristematic or
      division-competent states.

PMID- 15988560
TI  - Identification of cis-elements for ethylene and circadian regulation of the
      Solanum melongena gene encoding cysteine proteinase.
AB  - We have previously shown that the expression of SmCP which encodes Solanum
      melongena cysteine proteinase is ethylene-inducible and is under circadian
      control. To understand the regulation of SmCP, a 1.34-kb SmCP 5'-flanking region
      and its deletion derivatives were analyzed for cis-elements using GUS and luc
      fusions and by in vitro binding assays. Analysis of transgenic tobacco
      transformed with SmCP promoter-GUS constructs confirmed that the promoter region 
      415/+54 containing Ethylene Responsive Element ERE(-355/-348) conferred threefold
      ethylene-induction of GUS expression, while -827/+54 which also contains ERE(
      683/-676), produced fivefold induction. Using gel mobility shift assays, we
      demonstrated that each ERE binds nuclear proteins from both ethephon-treated and
      untreated 5-week-old seedlings, suggesting that different transcriptions factors
      bind each ERE under varying physiological conditions. Binding was also observed
      in extracts from senescent, but not young, fruits. The variation in binding at
      the EREs in fruits and seedlings imply that organ-specific factors may
      participate in binding. Analysis of transgenic tobacco expressing various SmCP
      promoter-luc constructs containing wild-type or mutant Evening Elements (EEs)
      confirmed that both conserved EEs at -795/-787 and -785/-777 are important in
      circadian control. We confirmed the binding of total nuclear proteins to EEs in
      gel mobility shift assays and in DNase I footprinting. Our results suggest that
      multiple proteins bind the EEs which are conserved in plants other than
      Arabidopsis and that functional EEs and EREs are present in the 5'-flanking
      region of a gene encoding cysteine proteinase.

PMID- 15988561
TI  - Suppression of the cysteine protease, aleurain, delays floret senescence in
      Brassica oleracea.
AB  - An aleurain-like protein, BoCP5, is up-regulated during harvest-induced
      senescence in broccoli floret and leaf tissue. BoCP5 is most closely related to
      an Arabidopsis protein (91%, AAF43041) and has 71% identity to barley aleurain
      (P05167). The mRNA for this gene accumulates within 6 h after harvest in broccoli
      florets, and its expression is reduced in tissue that has been held in senescence
      delaying treatments (e.g. water, sucrose feeding, controlled atmosphere). The
      gene is also expressed in leaves during aging-related and harvest-induced
      senescence. Analysis of protein bands that cross-react with antibodies raised to
      the bacterial BoCP5 fusion protein, revealed prominent immunoreactive bands at
      ca. 26, 28, 31, and 38 kD in floret tissue. The 31 kD band was absent in protein
      extracts from leaf tissue. Agrobacterium-mediated transformation was used to
      produce transgenic broccoli plants with down-regulated BoCP5. A reduction in the
      postharvest expression of BoCP5 in floret tissue was achieved for four transgenic
      lines in the current study. In three of these lines postharvest floret senescence
      (yellowing) was delayed, and florets contained significantly greater chlorophyll
      levels during postharvest storage at 20 degrees C than wild-type plants. Line 4
      showed the greatest down-regulation of BoCP5, and in this line postharvest
      protease activity remained at pre-harvest levels, and the yield of soluble
      proteins extracted from florets after harvest was significantly greater than that
      of wild-type tissue.

PMID- 15988562
TI  - Isolation and characterization of a polymorphic stigma-specific class III
      peroxidase gene from Senecio squalidus L. (Asteraceae).
AB  - A novel stigma-specific class III peroxidase gene, SSP (Stigma-Specific
      Peroxidase), has been isolated from the self-incompatible daisy Senecio squalidus
      L. (Asteraceae). Expression of SSP in flower buds is developmentally regulated,
      with maximal levels of expression coinciding with anthesis, when stigmas are most
      receptive to pollen and when self-incompatibility is fully developed. In situ
      hybridization revealed SSP expression to be localized exclusively to the
      specialized secretory epidermal cells (papillae) of the stigma, which receive and
      discriminate pollen. SSP is therefore the first tissue-specific and cell-specific
      peroxidase gene identified in a plant. SSP belongs to a distinct clade of class
      III plant peroxidases that possess two introns, instead of the more normal
      situation of three conserved introns. The deduced amino acid sequence of SSP
      revealed a 27 amino acid signal peptide, suggesting that the SSP protein is
      secreted to the cell wall of the stigmatic papillae. In-gel peroxidase activity
      assays showed that SSP has relatively low peroxidase activity compared to other,
      as yet uncharacterized, peroxidases present in stigmatic extracts. Six SSP
      alleles have been cloned from different lines of S. squalidus carrying a range of
      self-incompatibility (S)-alleles but there was no consistent association between
      the presence of a particular SSP allele and S-genotype indicating that SSP is not
      the female determinant of SSI in S. squalidus. Nevertheless, the precise
      expression of SSP in stigmatic papillae suggests that it may have a more general
      function in pollen-stigma interactions, or alternatively in protection of stigmas
      from pathogen attack. Extensive database screens have identified homologues of
      SSP in other plant species, but available expression data for these genes
      indicates that none are flower-specific, suggesting that SSP represents a new
      functional type of class III peroxidase specific to the stigma. We discuss the
      possible function(s) of S. squalidus SSP in pollen-stigma interactions and in
      protection of stigmas from pathogen attack.

PMID- 15988563
TI  - Cloning and expression of the tobacco CHLM sequence encoding Mg protoporphyrin IX
      methyltransferase and its interaction with Mg chelatase.
AB  - S-adenosyl-L-methionine:Mg-protoporphyrin IX methyltransferase (MgPMT) is an
      enzyme in the Mg branch of the tetrapyrrole biosynthetic pathway. The nucleotide
      sequence of tobacco (Nicotiana tabacum) CHLM was identified and the cDNA sequence
      was used to express the precursor, the mature and a truncated recombinant MgPMT
      for enzymatic activity tests and for the formation of polyclonal antibodies.
      Comparison of the mature and the truncated MgPMT revealed three critical amino
      acids at the N-terminus of MgPMT for the maintenance of enzyme activity. To
      assess the contribution of CHLM expression to the control of the metabolic flow
      in the tetrapyrrole pathway, CHLM transcripts and protein levels, the enzyme
      activity and the steady-state levels of Mg protoporphyrin and Mg protoporphyrin
      monomethylester were analysed during greening of seedlings and plant development
      as well as under day/night and continuous growth conditions. These expression
      studies revealed posttranslational activation of MgPMT during greening and
      light/dark-cycles. Using the yeast two-hybrid system physical interaction was
      demonstrated between MgPMT and the CHLH subunit of Mg chelatase. Activity of
      recombinant MgPMT expressed in yeast cells was stimulated in the presence of the
      recombinant CHLH subunit. Implications for posttranslational regulation of MgPMT
      are discussed for the enzymatic steps at the beginning of the Mg branch.

PMID- 15988564
TI  - Specific patterns of changes in wheat gene expression after treatment with three
      antifungal compounds.
AB  - The two fungicides azoxystrobin and fenpropimorph are used against powdery mildew
      and rust diseases in wheat (Triticum aestivumL). Azoxystrobin, a strobilurin,
      inhibits fungal mitochondrial respiration and fenpropimorph, a morpholin,
      represses biosynthesis of ergosterol, the major sterol of fungal membranes.
      Although the fungitoxic activity of these compounds is well understood, their
      effects on plant metabolism remain unclear. In contrast to the fungicides which
      directly affect pathogen metabolism, benzo(1,2,3) thiadiazole-7-carbothioic acid
      S-methylester (BTH) induces resistance against wheat pathogens by the activation
      of systemic acquired resistance in the host plant. In this study, we monitored
      gene expression in spring wheat after treatment with each of these agrochemicals
      in a greenhouse trial using a microarray containing 600 barley cDNA clones.
      Defence-related genes were strongly induced after treatment with BTH, confirming
      the activation of a similar set of genes as in dicot plants following salicylic
      acid treatment. A similar gene expression pattern was observed after treatment
      with fenpropimorph and some defence-related genes were induced by azoxystrobin,
      demonstrating that these fungicides also activate a defence reaction. However,
      less intense responses were triggered than with BTH. The same experiments
      performed under field conditions gave dramatically different results. No gene
      showed differential expression after treatment and defence genes were already
      expressed at a high level before application of the agrochemicals. These
      differences in the expression patterns between the two environments demonstrate
      the importance of plant growth conditions for testing the impact of agrochemicals
      on plant metabolism.

PMID- 15988565
TI  - Temporal evolution of the Arabidopsis oxidative stress response.
AB  - We have carried out a detailed analysis of the changes in gene expression levels
      in Arabidopsis thaliana ecotype Columbia (Col-0) plants during and for 6 h after
      exposure to ozone (O3) at 350 parts per billion (ppb) for 6 h. This O3 exposure
      is sufficient to induce a marked transcriptional response and an oxidative burst,
      but not to cause substantial tissue damage in Col-0 wild-type plants and is
      within the range encountered in some major metropolitan areas. We have developed
      analytical and visualization tools to automate the identification of expression
      profile groups with common gene ontology (GO) annotations based on the sub
      cellular localization and function of the proteins encoded by the genes, as well
      as to automate promoter analysis for such gene groups. We describe application of
      these methods to identify stress-induced genes whose transcript abundance is
      likely to be controlled by common regulatory mechanisms and summarized our
      findings in a temporal model of the stress response.

PMID- 15988566
TI  - Colonization of the Arabidopsis rhizosphere by fluorescent Pseudomonas spp.
      activates a root-specific, ethylene-responsive PR-5 gene in the vascular bundle.
AB  - Plants of which the roots are colonized by selected strains of non-pathogenic,
      fluorescent Pseudomonas spp. develop an enhanced defensive capacity against a
      broad spectrum of foliar pathogens. In Arabidopsis thaliana, this rhizobacteria
      induced systemic resistance (ISR) functions independently of salicylic acid but
      requires responsiveness to jasmonic acid and ethylene. In contrast to pathogen
      induced systemic acquired resistance (SAR), ISR is not associated with systemic
      changes in the expression of genes encoding pathogenesis-related (PR) proteins.
      To identify genes that are specifically expressed in response to colonization of
      the roots by ISR-inducing Pseudomonas fluorescens WCS417r bacteria, we screened a
      collection of Arabidopsis enhancer trap and gene trap lines containing a
      transposable element of the Ac/Ds system and the GUS reporter gene. We identified
      an enhancer trap line (WET121) that specifically showed GUS activity in the root
      vascular bundle upon colonization of the roots by WCS417r. Fluorescent
      Pseudomonas spp. strains P. fluorescens WCS374r and P. putida WCS358r triggered a
      similar expression pattern, whereas ISR-non-inducing Escherichia coli bacteria
      did not. Exogenous application of the ethylene precursor 1-aminocyclopropane-1
      carboxylate (ACC) mimicked the rhizobacteria-induced GUS expression pattern in
      the root vascular bundle, whereas methyl jasmonic acid and salicylic acid did
      not, indicating that the Ds element in WET121 is inserted in the vicinity of an
      ethylene-responsive gene. Analysis of the expression of the genes in the close
      vicinity of the Ds element revealed AtTLP1 as the gene responsible for the in cis
      activation of the GUS reporter gene in the root vascular bundle. AtTLP1 encodes a
      thaumatin-like protein that belongs to the PR-5 family of PR proteins, some of
      which possess antimicrobial properties. AtTLP1 knockout mutant plants showed
      normal levels of WCS417r-mediated ISR against the bacterial leaf pathogen
      Pseudomonas syringae pv. tomato DC3000, suggesting that expression of AtTLP1 in
      the roots is not required for systemic expression of ISR in the leaves. Together,
      these results indicate that induction of AtTLP1 is a local response of
      Arabidopsis roots to colonization by non-pathogenic fluorescent Pseudomonas spp.
      and is unlikely to play a role in systemic resistance.

PMID- 15988567
TI  - Translation initiation factors eIF4E and eIFiso4E are required for polysome
      formation and regulate plant growth in tobacco.
AB  - Eukaryotic initiation factor eIF4E plays a pivotal role in translation
      initiation. As a component of the ternary eIF4F complex, eIF4E interacts with the
      mRNA cap structure to facilitate recruitment of the 40S ribosomal subunit onto
      mRNA. Plants contain two distinct cap-binding proteins, eIF4E and eIFiso4E, that
      assemble into different eIF4F complexes. To study the functional roles of eIF4E
      and eIFiso4E in tobacco, we isolated two corresponding cDNAs, NteIF4E1 and
      NteIFiso4E1, and used these to deplete cap-binding protein levels in planta by
      antisense downregulation. Antibodies raised against recombinant NteIF4E1 detected
      three distinct cap-binding proteins in tobacco leaf extracts; NteIF4E and two
      isoforms of NteIFiso4E. The three cap-binding proteins were immuno-detected in
      all tissues analysed and were coordinately regulated, with peak expression in
      anthers and pollen. Transgenic tobacco plants showing significant depletion of
      either NteIF4E or the two NteIFiso4E isoforms displayed normal vegetative
      development and were fully fertile. Interestingly, NteIFiso4E depletion resulted
      in a compensatory increase in NteIF4E levels, whereas the down-regulation of
      NteIF4E did not trigger a reciprocal increase in NteIFiso4E levels. The antisense
      depletion of both NteIF4E and NteIFiso4E resulted in plants with a semi-dwarf
      phenotype and an overall reduction in polyribosome loading, demonstrating that
      both eIF4E and eIFiso4E support translation initiation in planta, which suggests
      their potential role in the regulation of plant growth.

PMID- 15988569
TI  - [Skin and soft tissue infections].
AB  - Infection can involve all layers of soft tissue. The severity of infection can
      range from a simple cutaneous infection to widespread necrosis of the skin,
      muscle, and fascia. While infections of soft tissue are common, and can usually
      be managed using conservative therapy or local surgery, clinicians should be
      aware of less commonly seen invasive infections that need immediate radical
      surgical debridement to treat the source adequately, contributing to improved
      survival.

PMID- 15988568
TI  - DET1 regulates the proteasomal degradation of LHY, a component of the Arabidopsis
      circadian clock.
AB  - Multiple photoreceptors contribute to the entrainment of the Arabidopsis
      circadian clock to daily cycles of light and darkness but little is known of the
      mechanisms by which these pathways affect the central oscillator. Here we
      investigate the epistatic interaction between DE-ETIOLATED 1 (DET1), a negative
      regulator of light-regulated gene expression, and LATE ELONGATED HYPOCOTYL (LHY),
      one of the core components of the circadian oscillator. The daily onset of LHY
      gene expression was advanced by approximately 4 h in det1-1 mutant plants,
      suggesting that the wild-type DET1 protein might function to repress its
      transcription during the subjective night. lhy-1 det1-1 double mutants exhibited
      arrhythmic expression of the CAB gene in constant light, similar to the lhy-1
      mutant parent. However, additive effects of the lhy-1 and det1-1 mutations on
      CAB2 expression patterns were revealed under diurnal light-dark cycles. Since the
      lhy-1 mutation causes aberrant, constitutive transcription of LHY from a
      constitutive viral promoter, this observation indicated that effects of DET1 were
      not mediated through the regulation of LHY transcription. Furthermore, the light
      driven, rhythmic accumulation of the LHY protein in the lhy-1 mutant was altered
      by the det1-1 mutation, suggesting that DET1 might regulate LHY expression at the
      post-transcriptional level. In vitro protein degradation assays demonstrated that
      the LHY protein is turned over rapidly through the proteasome pathway. Similar
      degradation was observed whether plant tissue was harvested during the light or
      dark portion of the diurnal cycle, but the process was significantly accelerated
      in det1-1 mutant extracts. These results indicate that the wild-type DET1 protein
      acts to inhibit the proteolytic turnover of the LHY protein, and suggest a
      mechanism for the period-shortening effect of the det1-1 mutation. These findings
      add to recent evidence suggesting a role for DET1 in a ubiquitination pathway and
      identify a substrate for DET1-regulated protein turn-over.

PMID- 15988570
TI  - [Kirschner wire migration in the contralateral lung after osteosynthesis of a
      clavicular fracture].
AB  - A 59-year-old patient was admitted complaining breathing-dependent pain in the
      lower right chest and increasing dyspnoea. Diminished breath sounds in the right
      lung and dullness in the lower right chest were found. Chest x-ray and
      complementary CT scan showed an intrapulmonary Kirschner wire and a large
      haematothorax but no pneumothorax. At 6 weeks before admission, the patient
      suffered a fracture of the medial left clavicle which was treated by closed
      reduction and percutaneous osteosynthesis with two Kirschner wires. The migrated
      K-wire and the haematoma were removed by video-assisted thoracoscopy without
      complications. Migration of Kirschner wires after clavicle fracture
      osteosynthesis is rare but dangerous. Migrations into the heart, lung, pulmonary
      vein or the cervical spinal cord have been recorded. Patients with K-wire
      osteosynthesis should be informed of the risk of wire migration and should
      undergo regular postoperative follow-ups including radiography every 2-4 weeks.

PMID- 15988571
TI  - The effects of DHBE and MLA on nicotine-induced enhancement of contextual fear
      conditioning in C57BL/6 mice.
AB  - RATIONALE: Previous research indicates that nicotine administration enhances
      hippocampus-dependent forms of learning, including contextual fear conditioning.
      This effect is blocked by mecamylamine, a noncompetitive, broad-spectrum
      nicotinic receptor antagonist. OBJECTIVES: The present study extends previous
      research by further characterizing the nicotinic acetylcholinergic receptor
      (nAChR) subtypes through which nicotine acts to enhance contextual fear
      conditioning. METHODS: C57BL/6J mice were trained with two conditioned stimulus
      (CS; 30 s, 85-dB white noise)-unconditioned stimulus (US; 2 s, 0.57-mA foot
      shock) pairings and tested 24 h later for contextual and cued fear conditioning.
      The effects of the alpha7 nAChR antagonist methyllycaconitine (MLA; 1.00, 10.00,
      and 20.00 mg/kg) and the effects of the alpha4beta2 nAChR antagonist dihydro-beta
      erythroidine (DHBE; 1.00, 3.00, and 6.00 mg/kg) on cued and contextual fear
      conditioning and on the enhancement of contextual fear conditioning by nicotine
      (0.25 mg/kg) were examined. RESULTS: We demonstrate that DHBE (all doses)
      administration attenuates the enhancing effect of nicotine on contextual fear
      conditioning, and MLA administration has no significant effect on the enhancement
      of contextual fear conditioning by nicotine. CONCLUSIONS: The data suggest that
      non-alpha7 nAChRs (most likely alpha4beta2 nAChRs) underlie the enhancement of
      contextual fear conditioning by nicotine.

PMID- 15988573
TI  - Purification and properties of a family-10 xylanase from Aureobasidium pullulans
      ATCC 20524 and characterization of the encoding gene.
AB  - An extracellular endo-1,4-beta-xylanase was purified from the culture supernatant
      of the ascomycete Aureobasidium pullulans ATCC 20524 grown on xylan. The purified
      enzyme was homogeneous as judged by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis and isoelectric focusing, which showed an apparent M (r) of 39
      kDa and a pI of 8.9, respectively. Xylanase activity was optimal at pH 6.0 and 70
      degrees C. The genomic DNA and cDNAs encoding this protein were cloned and
      sequenced. The xylanase gene (xynII) encoded a 26 amino acid signal peptide and a
      335 amino acid mature protein. DNA regions encoding the signal sequence and the
      mature protein were interrupted by introns of 56 and 73 bp, respectively. The
      xynII 5'-noncoding region had two consensus binding sites (5'-GCCARG-3') for the
      transcription factor PacC mediating pH regulation. Quantitative real-time
      polymerase chain reaction analysis revealed that the transcription levels at pH
      6.0 and 8.0 were 8-fold and 22-fold higher than that at pH 2.7, respectively. A
      cloned xynII cDNA was expressed and secreted in the yeast Pichia pastoris.
      Sequence alignment and phylogenetic analysis suggested that the XynII belongs to
      glycosyl hydrolase family 10 and that it is evolutionarily distant from two
      clusters formed by other family-10 xylanases.

PMID- 15988572
TI  - Long-term citalopram administration reduces responsiveness of HPA axis in
      patients with major depression: relationship with S-citalopram concentrations in
      plasma and cerebrospinal fluid (CSF) and clinical response.
AB  - RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a
      well-documented neurobiological finding in major depression. Moreover, clinically
      effective therapy with antidepressant drugs may normalize the HPA axis activity.
      OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects
      the function of the HPA axis in patients with major depression (DSM IV). METHODS:
      Twenty depressed patients (11 women and 9 men) were challenged with a combined
      dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH)
      stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16
      weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent
      reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the
      DEX/CRH test both in treatment responders and nonresponders within 16 weeks.
      There was a significant relationship between post-DEX baseline cortisol levels
      (measured before administration of CRH) and severity of depression at
      pretreatment baseline. Multiple linear regression analyses were performed to
      identify the impact of psychopathology and hormonal stress responsiveness and R/S
      CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of
      decrease in cortisol responsivity from pretreatment baseline to week 4 on drug
      [delta-area under the curve (AUC) cortisol] was a significant predictor
      (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e.,
      decrease in HAM-D21 total score). The model demonstrated that the interaction of
      CSF S-CIT concentrations and clinical improvement was the most powerful predictor
      of AUC cortisol responsiveness. CONCLUSION: The present study shows that
      decreased AUC cortisol was highly associated with S-CIT concentrations in plasma
      and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations
      rather than the R/S-CIT dose should be considered as an indicator of the
      selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis
      responsiveness as measured by AUC cortisol response.

PMID- 15988574
TI  - Direct mating between diploid sake strains of Saccharomyces cerevisiae.
AB  - Various auxotrophic mutants of diploid heterothallic Japanese sake strains of
      Saccharomyces cerevisiae were utilized for selecting mating-competent diploid
      isolates. The auxotrophic mutants were exposed to ultraviolet (UV) irradiation
      and crossed with laboratory haploid tester strains carrying complementary
      auxotrophic markers. Zygotes were then selected on minimal medium. Sake strains
      exhibiting a MATa or MATalpha mating type were easily obtained at high frequency
      without prior sporulation, suggesting that the UV irradiation induced
      homozygosity at the MAT locus. Flow cytometric analysis of a hybrid showed a
      twofold higher DNA content than the sake diploid parent, consistent with
      tetraploidy. By crossing strains of opposite mating type in all possible
      combinations, a number of hybrids were constructed. Hybrids formed in crosses
      between traditional sake strains and between a natural nonhaploid isolate and
      traditional sake strains displayed equivalent fermentation ability without any
      apparent defects and produced comparable or improved sake. Isolation of mating
      competent auxotrophic mutants directly from industrial yeast strains allows
      crossbreeding to construct polyploids suitable for industrial use without
      dependence on sporulation.

PMID- 15988575
TI  - The yeast split-ubiquitin system to study chloroplast membrane protein
      interactions.
AB  - Each photosynthetic complex within the thylakoid membrane consists of several
      different subunits. During formation of these complexes, numerous regulatory
      factors are required for the coordinated transport and assembly of the subunits.
      Interactions between transport/assembly factors and their specific polypeptides
      occur in a membraneous environment and are usually transient and short-lived.
      Thus, a detailed analysis of the underlying molecular mechanisms by biochemical
      techniques is often difficult to perform. Here, we report on the suitability of a
      genetic system, i.e. the yeast split-ubiquitin system, to investigate protein
      protein interactions of thylakoid membrane proteins. The data confirm the
      previously established binding of the cpSec-translocase subunits, cpSecY and
      cpSecE, and the interaction of the cpSec-translocase from Arabidopsis thaliana
      with Alb3, a factor required for the insertion of the light-harvesting
      chlorophyll-binding proteins into the thylakoid membrane. In addition, the
      proposed interaction between D1, the reaction center protein of photosystem II
      and the soluble periplasmic PratA factor from Synechocystis sp. PCC 6803 was
      verified. A more comprehensive analysis of Alb3-interacting proteins revealed
      that Alb3 is able to form dimers or oligomers. Interestingly, Alb3 was also shown
      to bind to the PSII proteins D1, D2 and CP43, to the PSI reaction center protein
      PSI-A and the ATP synthase subunit CF(0)III, suggesting an important role of Alb3
      in the assembly of photosynthetic thylakoid membrane complexes.

PMID- 15988576
TI  - The epidemic of type 2 diabetes is a statistical artefact.

PMID- 15988577
TI  - Atorvastatin does not decrease or delay diabetes onset in two different mouse
      models of type 1 diabetes.

PMID- 15988578
TI  - Implantation of primary cultured adipocytes that secrete insulin modifies blood
      glucose levels in diabetic mice.
AB  - AIM/HYPOTHESIS: In type 1 diabetic patients, basal insulin supplementation plays
      a central role in tight glycaemic control. Therefore, safe and steady
      supplementation of basal insulin is strongly desirable, despite the need for
      multiple injections. The aim of this study was to investigate a procedure for
      supplementation using genetically engineered, primary-cultured adipocytes in
      diabetic mice. METHODS: Furin-cleavable human proinsulin cDNA was transferred
      into murine primary-cultured adipocytes using a retroviral vector. The cells were
      implanted subcutaneously into streptozotocin-induced diabetic mice. RESULTS: The
      transfected cells secreted substantial amounts of mature insulin, as well as C
      peptide, into conditioned medium. Syngeneic implantation of the cells
      significantly improved hyperglycaemia and blood HbA(1)c concentrations in a
      manner that was dependent on cell number, without causing hypoglycaemia. The
      plasma insulin concentration was dependent on the implanted cell number, and the
      systemic effect of the circulating insulin was confirmed by marked improvement of
      body weight reduction and liver glycogen content. Additionally, surgical
      resection of the implants, in which the insulin secretion was immunologically
      confirmed after transplantation, diminished the glucose-lowering effect,
      suggesting that in vivo expression could be eliminated if necessary.
      CONCLUSIONS/INTERPRETATION: These results indicate that the autotransplantation
      of functionalised adipocytes may lead to a clinical application in the treatment
      of diabetes.

PMID- 15988579
TI  - Diabetic cardiomyopathy in uncomplicated type 2 diabetes is associated with the
      metabolic syndrome and systemic inflammation.

PMID- 15988580
TI  - Degradation products of proteins damaged by glycation, oxidation and nitration in
      clinical type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Hyperglycaemia in diabetes is associated with increased
      glycation, oxidative stress and nitrosative stress. Proteins modified
      consequently contain glycation, oxidation and nitration adduct residues, and
      undergo cellular proteolysis with release of corresponding free adducts. These
      free adducts leak into blood plasma for eventual renal excretion. The aim of this
      study was to perform a comprehensive quantitative analysis of protein glycation,
      oxidation and nitration adduct residues in plasma protein and haemoglobin as well
      as of free adducts in plasma and urine to quantify increased protein damage and
      flux of proteolytic degradation products in diabetes. METHODS: Type 1 diabetic
      patients (n=21) and normal healthy control subjects (n=12) were studied. Venous
      blood samples, with heparin anticoagulant, and 24-h urine samples were taken.
      Samples were analysed for protein glycation, oxidation and nitration adducts by a
      quantitative comprehensive screening method using liquid chromatography with
      triple quadrupole mass spectrometric detection. RESULTS: In type 1 diabetic
      patients, the concentrations of protein glycation, oxidation and nitration adduct
      residues increased up to three-fold in plasma protein and up to one-fold in
      haemoglobin, except for decreases in pentosidine and 3-nitrotyrosine residues in
      haemoglobin when compared with normal control subjects. In contrast, the
      concentrations of protein glycation and oxidation free adducts increased up to
      ten-fold in blood plasma, and urinary excretion increased up to 15-fold in
      diabetic patients. CONCLUSIONS/INTERPRETATION: We conclude that there are
      profound increases in proteolytic products of glycated and oxidised proteins in
      diabetic patients, concurrent with much lower increases in protein glycation and
      oxidation adduct residues.

PMID- 15988581
TI  - Imaging of protein movement induced by chromosomal breakage: tiny 'local' lesions
      pose great 'global' challenges.
AB  - Interruption of chromosomal integrity by DNA double-strand breaks (DSBs) causes a
      major threat to genomic stability. Despite tremendous progress in understanding
      the genetic and biochemical aspects of DSB-induced genome surveillance and repair
      mechanisms, little is known about organization of these molecular pathways in
      space and time. Here, we outline the key spatio-temporal problems associated with
      DSBs and focus on the imaging approaches to visualize the dynamics of DSB-induced
      responses in mammalian cells. We delineate benefits and limitations of these
      assays and highlight the key recent discoveries where live microscopy provided
      unprecedented insights into how cells defend themselves against genome
      destabilizing effects of DNA damage.

PMID- 15988582
TI  - Pre-medication to block [(18)F]FDG uptake in the brown adipose tissue of
      pediatric and adolescent patients.
AB  - BACKGROUND: Radiopharmaceutical uptake of [(18)F]2-deoxy-2-glucose (FDG) in brown
      adipose tissue is noted on 15-20% of positron emission tomography (PET) scans in
      children and adolescents. One report suggests that moderate-dose oral diazepam
      can partly or completely block FDG uptake in brown adipose tissue. OBJECTIVE: To
      determine whether [(18)F]FDG uptake in brown adipose tissue can be adequately
      blocked by pre-medication other than moderate-dose oral diazepam. MATERIALS AND
      METHODS: One hundred and eighteen [(18)F]FDG PET body imaging studies were
      performed in 69 pediatric patients with a variety of solid tumors. The mean age
      at the time of imaging was 12.9 years (range 1.2-22.6 years), and 33 studies were
      performed in patients younger than 10 years old. Seventy-six were performed in
      boys and 42 in girls. Patients were imaged using a dedicated PET camera. Pre
      medication was given in 88 studies: 45 received intravenous fentanyl (0.75-1.0
      mug/kg), 34 received low-dose oral diazepam (0.06 mg/kg) and 9 received moderate
      dose oral diazepam (0.10 mg/kg). Thirty patients received no pre-medication, 7 of
      whom were known to have received opiates for pain during the 12 h before the
      study. Six body regions in the neck and chest were reviewed for [(18)F]FDG uptake
      in brown adipose tissue. Uptake of FDG in brown fat was visually graded: 0 for no
      FDG uptake, 1 for low-grade uptake, 2 for moderate uptake, and 3 for intense
      uptake. Visual grades 2 and 3 were considered to interfere potentially with image
      interpretation in the neck and chest. Data were analyzed by multivariate
      regression using a Poisson distribution. RESULTS: [(18)F]FDG uptake in brown
      adipose tissue was most often seen in the lateral neck region and superior and
      lateral to the lungs (in 36 and 39 studies, respectively). Uptake was also seen
      near the costovertebral junctions (15 studies), in the superior and central neck
      in 7 studies and in the anterior mediastinum in 2. Brown adipose tissue uptake
      was thought to interfere potentially with image interpretation (visual grades 2
      and 3) in 19 studies-in 6 of 23 (26.1%) studies after no pre-medication and no
      opiates for pain, in 10 of 34 (29.4%) after low-dose oral diazepam, in 0 of 9
      (0%) after moderate-dose oral diazepam, in 3 of 45 (6.7%) after intravenous
      fentanyl, and in 0 of 7 (0%) after opiates prescribed for pain. Intravenous
      fentanyl reduced the grade of brown adipose tissue compared to no drug (P=0.0039)
      and low-dose diazepam (P=0.0024). Low-dose diazepam had no effect when compared
      to no drug (P=0.984). There were inadequate data for statistical testing of
      moderate-dose valium and opiates prescribed for pain. Children younger than 10
      years had lower uptake grades (P=0.019) than those older than 10 years. SUMMARY:
      The frequency of interfering [(18)F]FDG uptake in brown adipose tissue is reduced
      by intravenous fentanyl pre-medication, which appears to be an effective
      alternative to the existing standard pre-medication, moderate-dose oral diazepam.

PMID- 15988583
TI  - Sensitivity to detergents and plasmid curing in Enterococcus faecalis.
AB  - This research reports the sensitivity of a clinical isolate of Enterococcus
      faecalis to sodium N-lauroylsarcosinate (sarkosyl) and sodium dodecyl sulfate
      (SDS), as well as the efficiency of these detergents in curing the strain.
      Compared to Escherichia coli, Enterococcus faecalis was very sensitive to both
      detergents, with minimum inhibitory concentrations (MIC) for the latter being 100
      times lower than for Escherichia coli. The clinical isolate of Enterococcus
      faecalis used in this study exhibited plasmid-borne resistance to kanamycin (MIC
      2 mg/ml) and tetracycline (MIC 50 mug/ml); 3% curing was observed after growth in
      the presence of sarkosyl but no curing was observed after growth in the presence
      of either SDS or acridine orange. In contrast, 35% curing of plasmid-bearing
      Escherichia coli was observed after growth in the presence of either SDS or
      acridine orange, but none was observed after growth in the presence of sarkosyl.

PMID- 15988584
TI  - Purification and characterization of a serine alkaline protease from Bacillus
      clausii GMBAE 42.
AB  - An extracellular serine alkaline protease of Bacillus clausii GMBAE 42 was
      produced in protein-rich medium in shake-flask cultures for 3 days at pH 10.5 and
      37 degrees C. Highest alkaline protease activity was observed in the late
      stationary phase of cell cultivation. The enzyme was purified 16-fold from
      culture filtrate by DEAE-cellulose chromatography followed by (NH(4))(2)SO(4)
      precipitation, with a yield of 58%. SDS-PAGE analysis revealed the molecular
      weight of the enzyme to be 26.50 kDa. The optimum temperature for enzyme activity
      was 60 degrees C; however, it is shifted to 70 degrees C after addition of 5 mM
      Ca(2+) ions. The enzyme was stable between 30 and 40 degrees C for 2 h at pH
      10.5; only 14% activity loss was observed at 50 degrees C. The optimal pH of the
      enzyme was 11.3. The enzyme was also stable in the pH 9.0--12.2 range for 24 h at
      30 degrees C; however, activity losses of 38% and 76% were observed at pH values
      of 12.7 and 13.0, respectively. The activation energy of Hammarsten casein
      hydrolysis by the purified enzyme was 10.59 kcal mol(-1) (44.30 kJ mol(-1)). The
      enzyme was stable in the presence of the 1% (w/v) Tween-20, Tween-40,Tween-60,
      Tween-80, and 0.2% (w/v) SDS for 1 h at 30 degrees C and pH 10.5. Only 10%
      activity loss was observed with 1% sodium perborate under the same conditions.
      The enzyme was not inhibited by iodoacetate, ethylacetimidate, phenylglyoxal,
      iodoacetimidate, n-ethylmaleimidate, n-bromosuccinimide, diethylpyrocarbonate or
      n-ethyl-5-phenyl-iso-xazolium-3'-sulfonate. Its complete inhibition by
      phenylmethanesulfonylfluoride and relatively high k (cat) value for N-Suc-Ala-Ala
      Pro-Phe-pNA hydrolysis indicates that the enzyme is a chymotrypsin-like serine
      protease. K (m) and k (cat) values were estimated at 0.655 microM N-Suc-Ala-Ala
      Pro-Phe-pNA and 4.21 x 10(3) min(-1), respectively.

PMID- 15988585
TI  - Time-resolved echo-shared parallel MRA of the lung: observer preference study of
      image quality in comparison with non-echo-shared sequences.
AB  - The aim of this study was to evaluate the image quality of time-resolved echo
      shared parallel MRA of the lung. The pulmonary vasculature of nine patients
      (seven females, two males; median age: 44 years) with pulmonary disease was
      examined using a time-resolved MRA sequence combining echo sharing with parallel
      imaging (time-resolved echo-shared angiography technique, or TREAT). The
      sharpness of the vessel borders, conspicuousness of peripheral lung vessels,
      artifact level, and overall image quality of TREAT was assessed independently by
      four readers in a side-by-side comparison with non-echo-shared time-resolved
      parallel MRA data (pMRA) previously acquired in the same patients. Furthermore,
      the SNR of pulmonary arteries (PA) and veins (PV) achieved with both pulse
      sequences was compared. The mean voxel size of TREAT MRA was decreased by 24%
      compared with the non-echo-shared MRA. Regarding the sharpness of the vessel
      borders, conspicuousness of peripheral lung vessels, and overall image quality
      the TREAT sequence was rated superior in 75-76% of all cases. If the TREAT images
      were preferred over the pMRA images, the advantage was rated as major in 61-71%
      of all cases. The level of artifacts was not increased with the TREAT sequence.
      The mean interobserver agreement for all categories ranged between fair (artifact
      level) and good (overall image quality). The maximum SNR of TREAT did not differ
      from non-echo-shared parallel MRA (PA: TREAT: 273+/-45; pMRA: 280+/-71; PV:
      TREAT: 273+/-33; pMRA: 258+/-62). TREAT achieves a higher spatial resolution than
      non-echo-shared parallel MRA which is also perceived as an improved image
      quality.

PMID- 15988586
TI  - Low-dose multidetector-row CT angiography of the infra-renal aorta and lower
      extremity vessels: image quality and diagnostic accuracy in comparison with
      standard DSA.
AB  - To investigate the possibility of reducing X-ray exposure during multidetector
      row spiral computed tomographic (MDCT) angiography and to compare the image
      quality and diagnostic accuracy of different dosages with digital subtraction
      angiography (DSA) in the evaluation of the infra-renal aorta and lower
      extremities vessels. Seventy-five patients, randomly divided into three groups of
      25 patients each, were evaluated for atherosclerotic disease with four-row spiral
      CT angiography (4x2.5 mm) and DSA. MDCT scanning parameters were kept constant,
      except for milliamperage (mAs): group A: 50 mAs; group B: 100 mAs; group C: 130
      mAs. Images were analysed by two vascular radiologists in consensus. DSA
      represented the standard of reference. The diagnostic value of MDCT and total
      radiation exposure were evaluated for each data set. The simulated effective dose
      was 3.7 mSv for 50 mAs, 8.2 mSv for 100 mAs and 13.7 mSv for 130 mAs for men, and
      4 mSv for 50 mAs, 8.9 mSv for 100 mAs and 14.8 mSv for 130 mAs for women. The
      dose reduction was 74% for group A and 40% for group B. The evaluation of the
      presence and degree of stenoses revealed a sensitivity, specificity, accuracy,
      PPV and NPV of 96%, 94%, 95%, 83% and 99% for Group A (50 mAs), 96%, 96%, 96%,
      89% and 99% for Group B (100 mAs) and 98%, 96%, 97%, 91% and 100% for the
      standard dose protocol, Group C (130 mAs). Low-dose scanning is thus a feasible
      and accurate option for four-row CT angiography of the peripheral vessels. This
      technique provides substantial reduction of the radiation dose delivered to the
      patient while maintaining optimal diagnostic accuracy.

PMID- 15988587
TI  - Testis calcification of the tunica albuginea.

PMID- 15988588
TI  - ATP elicits inward currents in isolated vasopressinergic neurohypophysial
      terminals via P2X2 and P2X3 receptors.
AB  - Effects of extracellular adenosine tri-phosphate (ATP) on ionic currents were
      investigated using the perforated-patch whole-cell recording technique on
      isolated terminals of the Hypothalamic Neurohypophysial System (HNS). ATP induced
      a current response in 70% of these isolated terminals. This inwardly-rectifying,
      inactivating current had an apparent reversal near 0 mV and was dose-dependent on
      ATP with an EC50=9.6+/-1.0 microM. In addition, current amplitudes measured at
      maximal ATP concentrations and optimum holding potentials had a current density
      of 70.8 pA pF(-1) and were greatly inhibited by suramin and PPADS. Different
      purinergic receptor agonists were tested, with the following efficacy: ATP > or =
      2-methylthioATP > ATP-gamma-S > Bz-Bz-ATP > alpha,beta-methylene-ATP > beta,gamma
      methylene-ATP. However, UTP and ADP were ineffective. These data suggest the
      involvement of a P2X purinergic receptor in the ATP-induced responses.
      Immunocytochemical labeling in vasopressinergic terminals indicates the existence
      of P2X(2,3,4, and 7), but not P2X6 receptors. Additionally, P2X(2 and 3) were not
      found in terminals which labeled for oxytocin. In summary, the EC50, decay,
      inactivation, and pharmacology indicate that a functional mixture of P2X(2 and 3)
      homomeric receptors mediate the majority of the ATP responses in vasopressinergic
      HNS terminals. We speculate that the characteristics of these types of receptors
      reflect the function of co-released ATP in the terminal compartment of these and
      other CNS neurons.

PMID- 15988589
TI  - Functional role of TRPC channels in the regulation of endothelial permeability.
AB  - The endothelial cells (ECs) form a semipermeable barrier between the blood and
      the tissue. An important function of the endothelium is to maintain the integrity
      of the barrier function of the vessel wall. Ca(2+) signaling in ECs plays a key
      role in maintaining the barrier integrity. Transient receptor potential canonical
      (TRPC) channels are mammalian homologs of Drosophila TRP Ca(2+)-permeable
      channels expressed in EC. TRPC channels are thought to function as a Ca(2+) entry
      channel operated by store-depletion as well as receptor-activated channels in a
      variety of cell types, including ECs. Inflammatory mediators such as thrombin,
      histamine, bradykinin, and others increase endothelial permeability by actin
      polymerization-dependent EC rounding and formation of inter-endothelial gaps, a
      process critically dependent on the increase in EC cytosolic [Ca(2+)]
      ([Ca(2+)](i)). Increase in endothelial permeability depends on both intracellular
      Ca(2+) release and extracellular Ca(2+) entry through TRPC channels. This review
      summarizes recent findings on the role of TRPC channels in the mechanism of
      Ca(2+) entry in ECs, and, in particular, the role of TRPC channels in regulating
      endothelial barrier function.

PMID- 15988590
TI  - TRPV4 and the mammalian kidney.
AB  - Transient receptor potential vanilloid 4 (TRPV4) was identified as the mammalian
      homologue of the Caenorhabditis elegans osmosensory channel protein, OSM-9. In
      mammals, TRPV4 is activated by a variety of stimuli including thermal stress,
      fatty acid metabolites, and hypotonicity. Two distinct mechanisms have been
      described through which TRPV4 may be activated by hypotonicity: one involves the
      Src family of nonreceptor protein tyrosine kinases, whereas a second is mediated
      via arachidonic acid metabolites. TRPV4 likely plays a role in systemic
      osmoregulation; accordingly, it is expressed in the blood-brain barrier-deficient
      osmosensory nuclei of the hypothalamus. TRPV4 is also abundantly expressed in the
      kidney, and its precisely demarcated distribution along the kidney tubule permits
      speculation about a physiological role in this tissue. TRPV4-expressing and TRPV4
      negative tubule segments co-exist at all levels of the kidney, from the cortex
      through the inner medulla. It is conceivable that basolaterally expressed TRPV4
      transmits signals arising in the interstitium (e.g, changing tonicity) to more
      distal tubule segments where "fine-tuning" of the incipient urine takes place.

PMID- 15988591
TI  - Maintenance of stimulus-secretion coupling and single beta-cell function in
      cryopreserved-thawed human islets of Langerhans.
AB  - Studies of stimulus-secretion coupling in human beta-cells have been hampered by
      poor availability of tissue due to variability of the supply of cadaver pancreati
      and in the adequacy of enzymatic liberation of islets as well as by the shunting
      of isolates into transplant trials. Here we establish that aliquots of islets,
      several from high-quality but low-yield islet isolates (50,000-100,000 islets),
      cryopreserved and then thawed as needed, respond to glucose in a calcium- and
      metabolic-dependent fashion. Insulin secretion is modulated by blockers of
      voltage-dependent Na+ and Ca2+ channels, and paracrine hormones (glucagon and
      somatostatin) in manners indistinguishable from fresh tissue preparations. Using
      single-cell electrophysiological and electrochemical assays we demonstrate that
      single beta-cells from cryopreserved islets display (1) stimulus-depolarization
      coupling based on rapid closure of K+ (ATP) channels; (2) action potential
      electrogenesis with upstrokes based on voltage-dependent Na and Ca currents; and
      (3) Ca2+ entry-mediated depolarization-exocytosis coupling sustained over
      multiple bouts of stimulation and modulated by paracrine hormones. All of these
      features are indistinguishable from those seen in single cells from freshly
      harvested islets. These results support the utility of cryopreservation, even of
      low-yield but functional isolates, as a means of ensuring a steady source of
      repeatedly accessible tissue for research on normal and diabetic islets.

PMID- 15988592
TI  - NH3 and NH4+ permeability in aquaporin-expressing Xenopus oocytes.
AB  - We have shown recently, in a yeast expression system, that some aquaporins are
      permeable to ammonia. In the present study, we expressed the mammalian aquaporins
      AQP8, AQP9, AQP3, AQP1 and a plant aquaporin TIP2;1 in Xenopus oocytes to study
      the transport of ammonia (NH3) and ammonium (NH4+) under open-circuit and voltage
      clamped conditions. TIP2;1 was tested as the wild-type and in a mutated version
      (tip2;1) in which the water permeability is intact. When AQP8-, AQP9-, AQP3- and
      TIP2;1-expressing oocytes were placed in a well-stirred bathing medium of low
      buffer capacity, NH3 permeability was evident from the acidification of the
      bathing medium; the effects observed with AQP1 and tip2;1 did not exceed that of
      native oocytes. AQP8, AQP9, AQP3, and TIP2;1 were permeable to larger amides,
      while AQP1 was not. Under voltage-clamp conditions, given sufficient NH3, AQP8,
      AQP9, AQP3, and TIP2;1 supported inwards currents carried by NH4+. This
      conductivity increased as a sigmoid function of external [NH3]: for AQP8 at a
      bath pH (pH(e)) of 6.5, the conductance was abolished, at pH(e) 7.4 it was half
      maximal and at pH(e) 7.8 it saturated. NH4+ influx was associated with oocyte
      swelling. In comparison, native oocytes as well as AQP1 and tip2;1-expressing
      oocytes showed small currents that were associated with small and even negative
      volume changes. We conclude that AQP8, AQP9, AQP3, and TIP2;1, apart from being
      water channels, also support significant fluxes of NH3. These aquaporins could
      support NH4+ transport and have physiological implications for liver and kidney
      function.

PMID- 15988593
TI  - Surgery for metastatic renal cell cancer.
AB  - Renal cell carcinoma (RCC) often presents in its metastatic form, or progresses
      after curative treatment. While the management of metastatic RCC has historically
      been mainly surgical, contemporary approaches often incorporate systemic
      immunotherapy. This review examines the current indications and scope of surgical
      treatment of patients with metastatic RCC. Surgery is sometimes indicated for
      symptom palliation at either the primary or secondary sites. However, other less
      invasive therapies may be equally effective, and should be considered carefully.
      Cytoreductive surgery prior to immunotherapy appears to confer a survival
      advantage, but only selected patients are suitable for this treatment regimen.
      Primary immunotherapy followed by surgical removal of the tumour in partial
      responders is an alternative treatment strategy, which has not yet been evaluated
      as in randomized trials. As immunotherapy develops further, the precise timing
      and role of surgery in multimodality treatment will need to be carefully
      evaluated. Occasionally, the complete surgical excision of metastases, and the
      primary tumour, if present, is feasible and this may prolong survival.
      Empirically, it would seem that such patients should also be treated with
      adjuvant immunotherapy, as eventual relapse is frequent. Surgery with the aim of
      inducing spontaneous tumour regression is not justifiable, given the rarity of
      this phenomenon.

PMID- 15988594
TI  - New tined lead electrode in sacral neuromodulation: experience from a multicentre
      European study.
AB  - The use of a new tined lead electrode for sacral neuromodulation (SNS) was
      evaluated in a European study including 127 patients with chronic voiding
      dysfunction. The tined lead can be implanted during the first stage of the SNS
      procedure, which makes a longer test period possible before implanting the pulse
      generator in a second stage. Implantation of the tined lead was performed under
      local anaesthesia in 89% of patients. Screening lasted on average 30 days.
      Screening with the tined lead was considered successful by the physicians in 77%
      of patients (n=72). In 74% of first stage patients (n=70), at least 50%
      improvement in the main symptoms versus baseline was obtained. This was sustained
      for up to 6 weeks. All of these patients received the pulse generator in a second
      stage. The outcome of this study supports the use of the tined lead electrode as
      a screening tool in SNS therapy.

PMID- 15988595
TI  - Auditory sequence learning: differential sensitivity to task relevant and task
      irrelevant sequences.
AB  - Using a serial reaction time task, this study examines whether learning of
      auditory sequences is possible without a corresponding motor response, i.e., by
      listening alone. The dual sequence paradigm used by Mayr (in Journal of the
      Experimental Psychology: Learning memory and cognition 22:350-354, 1996,
      Experiment 1) was adapted to the auditory domain. Four different actors spoke the
      same four colour words. These were presented such that speaker identity followed
      one sequence, and the word spoken followed a different sequence. Subjects were
      asked to respond (with a key press) to one of these dimensions (identity or
      word), and ignore the other. Results showed learning for either type of stimulus,
      but only when it was responded to. No learning of either type of auditory
      sequence by listening alone was found. The results add evidence to visual
      implicit learning studies that have failed to find learning of event sequences
      when spatial or response selection was not an important factor in processing. The
      findings are discussed in the context of implicit learning as a general and
      fundamental cognitive process.

PMID- 15988596
TI  - The development of a dialogue between cortex and midbrain to integrate
      multisensory information.
AB  - The anterior ectosylvian (AES) and rostral lateral suprasylvian (rLS) sulci send
      critical signals to multisensory superior colliculus (SC) neurons that enable
      them to integrate information from different senses. When either of these areas
      is temporarily deactivated in adult animals, the ability of SC neurons to
      integrate multisensory information and, thereby, enhance their responses to cross
      modal stimuli is temporarily compromised. As a consequence, the ability to use
      cross-modal stimuli to enhance SC-mediated behavioral performance is also
      compromised. In contrast, removal of either one of these areas during early life
      has little effect on the development of multisensory processes in the SC or on SC
      mediated multisensory behaviors and these animals seem very similar to normal
      controls. These observations suggest that there is considerable plasticity in
      these cortico-collicular systems during early life, with each area able to
      compensate for the early loss of the other. However, when both AES and rLS are
      removed early in life, there appears to be no compensation. The SC neurons now
      deal with sensory stimuli, even those embedded in multisensory complexes, as if
      they were there alone, precluding any SC-mediated behavioral benefit to cross
      modal stimuli.

PMID- 15988598
TI  - The role of systemic hypermobility and condylar hypermobility in
      temporomandibular joint dysfunction syndrome.
AB  - OBJECTIVE: To evaluate the risk of temporomandibular joint dysfunction (TMD),
      when both systemic joint hypermobility (SJH) and localized condylar hypermobility
      (LCH) exist. MATERIALS AND METHODS: Sixty-four consecutive outpatients with
      temporomandibular joint clicking or pain, and 77 sex- and age-matched control
      subjects, were recruited in the study. LCH was diagnosed when condylar
      subluxation was present, and SJL was diagnosed by using Beighton's method. The
      frequency of symptoms, mean mouth opening, and the frequency of subjects with SJL
      and LCH were the main outcome measures. RESULTS: Out of the 64 patients, 16
      patients were suffering from pain, 20 patients from joint-clicking and 28
      patients from both. Both SJH and LCH were more frequently observed in those
      patients with TMD than in control subjects. The risk of TMD was higher if LCH and
      SJH existed jointly. CONCLUSION: Both systemic and localized hypermobility may
      have a role in the etiology of TMD.

PMID- 15988597
TI  - On the use of superadditivity as a metric for characterizing multisensory
      integration in functional neuroimaging studies.
AB  - A growing number of brain imaging studies are being undertaken in order to better
      understand the contributions of multisensory processes to human behavior and
      perception. Many of these studies are designed on the basis of the physiological
      findings from single neurons in animal models, which have shown that multisensory
      neurons have the capacity for integrating their different sensory inputs and give
      rise to a product that differs significantly from either of the unisensory
      responses. At certain points these multisensory interactions can be
      superadditive, resulting in a neural response that exceeds the sum of the
      unisensory responses. Because of the difficulties inherent in interpreting the
      results of imaging large neuronal populations, superadditivity has been put forth
      as a stringent criterion for identifying potential sites of multisensory
      integration. In the present manuscript we discuss issues related to using the
      superadditive model in human brain imaging studies, focusing on population
      responses to multisensory stimuli and the relationship between single neuron
      measures and functional brain imaging measures. We suggest that the results of
      brain imaging studies be interpreted with caution in regards to multisensory
      integration. Future directions for imaging multisensory integration are discussed
      in light of the ideas presented.

PMID- 15988599
TI  - Dysautonomia in fibromyalgia syndrome: sympathetic skin responses and RR interval
      analysis.
AB  - This study was planned to investigate the dysfunction of the autonomic nervous
      system in fibromyalgia syndrome (FM) using sympathetic skin responses (SSR) and
      RR interval analysis. Thirty-four FM and 22 healthy subjects were recruited for
      the study. They were questioned for symptoms that are characteristic for FM and
      medical outcome study short form-36 (SF-36) was used to determine the quality of
      life of the subjects. Tender points were counted and the disease duration was
      noted. SSR was recorded from palm and sole with stimulation of contralateral
      median and tibial nerves respectively. R-R interval variation was evaluated at
      rest (R%) and during deep breathing (DR%). The mean ages of the patients were
      37+/- 10.2 and 37+/-10.6, respectively. The mean tender point count was 14.9+/
      2.3 and the disease duration was 16.6+/-12.1 months. The symptoms were discrepant
      in FM (P<0.001). The scores of the eight items of SF-36 in FMS patients were
      significantly lower than the control group (P<0.001). We could not elicit SSR in
      five FM patients (15%) from the sole and in two patients (6%) from the palm. The
      latencies of SSR recorded from both palms and soles of FM patients were
      significantly longer than healthy subjects (P<0.001). The mean amplitude of SSR
      recorded from both palm and sole was not statistically different from control
      subjects (P>0.05). RRIV obtained from FM and the control subjects at rest and
      during deep breathing showed that the decrease in DR% was significant compared to
      normal subjects (P<0.001). As a result, we can state that sympathetic as well as
      parasympathetic nervous system dysfunction occurs in FM patients and this
      abnormality could be determined by SSR and RRIV analysis.

PMID- 15988600
TI  - Catalase and PPARgamma2 genotype and risk of rheumatoid arthritis in Koreans.
AB  - Catalase (CAT) and peroxisome proliferator activated receptor-gamma2 (PPARgamma2)
      are important regulators of oxidative stress and inflammation, and may contribute
      to the development of rheumatoid arthritis (RA). We investigated the association
      between CAT and PPARgamma2 genotypes and risk and severity of RA using 474 cases
      and 400 controls. Genotyping for the -262C-->T polymorphism of CAT and the
      Pro12Ala polymorphism of PPARgamma2 was performed by PCR-RFLP analysis. Severity
      of RA was assessed by the anatomical stage according to Steinbrocker, and a
      Korean language version of a Health Assessment Questionnaire (KHAQ). No
      association was observed between CAT and PPARgamma2 genotypes and risk of RA. Our
      results suggest that genetic polymorphisms of CAT and PPARgamma2 do not play a
      significant role in the susceptibility to RA among Koreans.

PMID- 15988601
TI  - Polymyalgia rheumatica in primary Sjogren's syndrome.
AB  - The aim of the study was to describe the clinical and laboratory aspects of
      primary Sjogren's syndrome (pSS) associated with polymyalgia rheumatica (PMR).
      The retrospective study compares the clinical and laboratory aspects of patients
      with pSS associated with PMR on a relatively large cohort of patients (n=16) and
      pSS patients without PMR (n=531). The prevalence of PMR among pSS patients was
      3%, while in the average population, the prevalence of PMR is only 0.75%. PMR
      developed 8.7 years after the diagnosis of pSS in the older female pSS population
      (over 50 years of age), and in those with only glandular features. Interestingly
      the pSS/PMR patients had hypo gammaglobuline levels, while in the pSS patient
      group hypergammaglobulinaemia presented. Furthermore, positive ANA serology was
      more frequent among pSS/PMR patients. Since the clinical management of pSS/PMR is
      different from pSS, a better understanding of this clinical entity is essential.

PMID- 15988602
TI  - Hepatozoon spp.: pathological and partial 18S rRNA sequence analysis from three
      Brazilian dogs.
AB  - Molecular and histopathological studies were carried out on samples from three
      Brazilian dogs with persistent hepatozoonosis parasitemia. Canine hepatozoonosis
      was confirmed by finding gametocytes in blood smears. Histopathological
      examination of skeletal muscle biopsy revealed muscle degeneration and atrophy,
      and degenerating/regenerating myofibers, similar to the muscle degeneration
      caused by Hepatozoon americanum . However, the large cystic structures typical of
      H. americanum were not observed in muscle biopsies from these dogs. Partial 18S
      rRNA sequences amplified by PCR from the three Brazilian samples demonstrated
      closest similarity to the Hepatozoon sp. Fukuoka described in Japan (>99%
      identity). These results indicate that both additional clinical cases and genes
      need examination in order to determine the phylogenetic relatedness among canid
      Hepatozoon species.

PMID- 15988603
TI  - Ultrastructure of the spermatozoon of Raillietina (Raillietina) baeri
      (Cyclophyllidea, Davaineidae) an intestinal parasite of the multimammate rat,
      Mastomys huberti (Rodentia, Muridae).
AB  - The mature Raillietina (Raillietina) baeri spermatozoon exhibits an apical cone
      of electron-dense material about 2.5 microm long and 0.5 microm wide and two
      helicoidal crest-like bodies roughly 100-125 nm thick. The latter are of
      different lengths, spiralized and stand in an angle of about 50 degrees with the
      spermatozoon axis. The axoneme is of the 9 + "1" pattern and does not reach the
      posterior extremity of the gamete. The nucleus is an electron-dense cord coiled
      in a spiral around the axoneme. The cytoplasm exhibits a posterior densification
      and contains few small electron-dense granules in regions I, II and V of the
      spermatozoon. In regions III and IV, it is divided into irregular compartments by
      walls of electron-dense material. The cortical microtubules are spiralized and
      make an angle of 40-50 degrees to the spermatozoon axis. In this work, we
      describe, for the first time, a spermatozoon of a davaineidaean cestode parasitic
      of mammals. This has enabled us to show a wide apical cone, which has never been
      described before in a cyclophyllidean species the spermatozoon of which has two
      crest-like bodies.

PMID- 15988604
TI  - [Haemostaseology].
AB  - The design and development of new antithrombotics, i.e. anticoagulants and
      antiplatelet drugs, is a rapidly expanding area of pharmacological research. New
      anticoagulants, i.e. inhibitors of thrombin formation and action have been
      developed and some of them are already in clinical use. This includes hirudin and
      its analogs, such as bivalirudin. In contrast to heparins, these compounds as
      well as low-molecular weight inhibitors of thrombin and factor Xa directly
      inhibit thrombus-associated generation and action of thrombin, eventually
      associated with a reduced bleeding tendency. Orally active compounds are
      available and currently subject of clinical trials. It appears possible that
      these new agents may replace cumarins as oral anticoagulants, specifically in
      long-term use, in the near future. The introduction of clopidogrel marks another
      important development in the field of antiplatelet drugs. Synergistic actions of
      this compound with acetylsalicylic acid and GP-IIb/IIIa-antagonists because of
      their different mode of action enhance the antithrombotic potential considerably
      and have been clinically confirmed. Despite of this optimistic outlook, the
      individual risk/benefit ratio of these new drugs, in particular in the area of
      anticoagulants, still needs to be defined.

PMID- 15988606
TI  - [Modern mycologic diagnosis. Problems in the daily practice].
AB  - Mycological diagnosis is an integral part of dermatology. Modern aspect include
      not only the identification of causative agents but also sensitivity testing
      against topical and systemic antimycotic agents and more detailed molecular
      biological diagnosis using fingerprinting and PCR. In routine practice, the
      essential question is if a fungal infection is present or not. A positive culture
      identification should precede use of systemic antimycotic agents especially when
      dealing with advanced onychomycosis, tinea capitis and chronic candidosis.
      Determination of resistance is important when dealing with recurrent infections
      with special candidal species. PCR is most useful in diagnosing otherwise
      difficult to identify causative agents and in analyzing the chain of infection.

PMID- 15988605
TI  - The recycling of carbon in glucose, lactate and alanine in sheep.
AB  - Pregnant ewes with catheters implanted in an artery and the uterine and recurrent
      tarsal veins were infused at a constant rate with U-(14)C-labelled glucose,
      alanine or bicarbonate. Measurements were made of the overall and local
      fractional contribution of glucose and alanine to CO(2) production and of the
      extent of interconversion of these metabolites. In the whole animal, by coupling
      the results with the authors' previous study of lactate metabolism, a solution
      was obtained to an open unrestricted 4-compartment model of the exchange of
      carbon between glucose, lactate, alanine and CO(2). A more limited study was made
      with non-pregnant sheep because complete data for lactate interactions with
      alanine were not available. Our analysis of glucose/lactate/alanine/CO(2)
      interactions in pregnant sheep suggests that about two-thirds of the glycogenic
      carbon was oxidised fairly directly to CO(2). There was relatively little
      recycling of glucose carbon through lactate and alanine so that most of the
      remaining glycogenic carbon was stored as product with relatively long turnover
      time. It is possible that much of this was in the form of muscle glycogen, and
      analysis of glycogenic carbon exchange across the hind limb muscle was consistent
      with this conclusion. In non-pregnant ewes, the findings, although incomplete,
      suggested that there were no great differences from the findings in pregnant
      ewes.

PMID- 15988607
TI  - Chromosome aberration and environmental physical activity: Down syndrome and
      solar and cosmic ray activity, Israel, 1990-2000.
AB  - The possibility that environmental effects are associated with chromosome
      aberrations and various congenital pathologies has been discussed previously.
      Recent advances in the collection and computerization of data make studying these
      potential associations more feasible. The aim of this study was to investigate a
      possible link between the number of Down syndrome (DS) cases detected prenatally
      or at birth yearly in Israel over a 10-year period compared with the levels of
      solar and cosmic ray activity 1 year before the detection or birth of each
      affected child. Information about 1,108,449 births was collected for the years
      1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of
      DS were detected prenatally or at birth--138 in the non-Jewish community and
      1,172 in the Jewish population. Solar activity indices--sunspot number and solar
      radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999--were compared with the
      number of DS cases detected. Pearson correlation coefficients (r) and their
      probabilities (P) were established for the percentage of DS cases in the whole
      population. There was a significant inverse correlation between the indices of
      solar activity and the number of cases of DS detected--r=-0.78, P=0.008 for
      sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that
      cosmophysical factors inversely related to solar activity play a role in the
      pathogenesis of chromosome aberrations should be considered. We have confirmed a
      strong trend towards an association between the cosmic ray activity level and the
      incidence of DS.

PMID- 15988608
TI  - Variations in the protective immune response against streptococcal superantigens
      in populations of different ethnicity.
AB  - Superantigens (SAgs) from group A streptococcus (GAS) are potent T cell mitogens,
      and have been suggested to play a role in severe streptococcal disease.
      Neutralizing antibodies protect against SAg-mediated disease and their levels
      should therefore be inversely related to severe streptococcal infection.
      Neutralizing anti-SAg titers in patients with severe GAS infection and patients
      without disease were compared in two separate groups. The first group comprised
      patients with invasive GAS disease from New Zealand European, Maori, and Pacific
      Island descent. The second group comprised Aboriginal Australian individuals with
      rheumatic heart disease and/or a past history of acute rheumatic fever. Patients
      sera were tested for their ability to neutralize T cell mitogenicity of
      recombinant streptococcal SAgs as a measure of functional SAg-neutralizing
      antibody concentration. In both studies, no inverse correlation was observed
      between disease and the level of serum SAg-neutralizing activity. Notably, much
      higher levels of natural immunity to all streptococcal SAgs were found in New
      Zealand Maori, New Zealand Pacific Island, and Aboriginal Australian individuals,
      suggesting a high degree of natural exposure and seroconversion in these groups
      compared to the New Zealand European cohort. Levels of serum antibodies against
      SAgs could not be used to predict disease susceptibility in groups with existing
      high levels of SAg-neutralizing antibodies.

PMID- 15988609
TI  - Significance of the mechanical environment during regeneration of the
      intervertebral disc.
AB  - The prevalence of low back pain is high, and the intervertebral (IV) disc is
      regarded as one of the major causes. Various approaches have been reported to
      either slow down disc degeneration or to repair/regenerate the disc. So far, the
      effect of the mechanical environment has not been addressed in these approaches,
      although several investigations have shown its influence on other mesenchymal
      tissues. In this paper, we propose that the biophysical stimuli from the
      mechanical environment can directly influence cell type, as well as their
      metabolic activity during repair/regeneration of the IV disc. To demonstrate the
      potential of this idea, data from the literature, as well as explorative
      experimental results, are presented.

PMID- 15988610
TI  - Non-invasive imaging of cardiac transgene expression with PET: comparison of the
      human sodium/iodide symporter gene and HSV1-tk as the reporter gene.
AB  - PURPOSE: Genes encoding for intracellular enzymes or transmembrane proteins are
      suitable as reporters, but may differ in terms of applicability for cardiac
      imaging. The aim of this study was to compare the human sodium iodide symporter
      gene (hNIS) with the herpes simplex virus type 1 thymidine kinase gene (HSV1-tk)
      as the reporter gene in non-invasive imaging of cardiac transgene expression with
      positron emission tomography (PET). METHODS: Equal doses of adenoviral vectors
      encoding for hNIS, wild-type HSV1-tk, mutant HSV1-sr39tk or LacZ as the control
      gene were directly injected into the myocardium of 34 animals. Two days later,
      dynamic PET was performed with a clinical scanner, using reporter probes specific
      for the respective reporter gene. Imaging with (13)N-ammonia was also performed
      to identify cardiac regions of interest. RESULTS: Kinetics differed
      significantly: (124)I as the probe for hNIS showed rapid early uptake, remaining
      stable over time. Maximal myocardial concentration was 3.61+/-1.15%. The
      nucleoside (18)F-FHBG, as the specific probe for HSV1-sr39tk, showed increasing
      uptake over time, but maximal accumulation was significantly lower (1.45+/-0.54%,
      P=0.0009). (124)I-FIAU, as the specific probe for wild-type HSV1-tk, showed early
      uptake with subsequent washout. Maximal accumulation was lowest (0.63+/-0.23%,
      P<0.0001). Post-mortem analysis by autoradiography and gamma counting confirmed
      the in vivo data. CONCLUSION: Reporter genes encoding for transporter proteins
      such as hNIS are an attractive alternative to overexpression of intracellular
      enzymes for cardiac gene product imaging. hNIS yielded higher signal intensity
      and imaging contrast for PET than did HSV1-tk and HSV1-sr39tk. Therefore, this
      approach may be preferable for the future monitoring of cardiac gene- or cell
      based therapy.

PMID- 15988611
TI  - Early plaque formation on fibre-reinforced composites in vivo.
AB  - In the present study, two different fibre-reinforced composites (FRCs) (glass and
      polyethylene FRC), dental ceramic and restorative composite were compared with
      respect to early plaque formation in vivo. Disc-shaped specimens were randomly
      distributed among the upper first and second molars of 14 healthy adult
      volunteers. Plaque samples were collected 24 h after the attachment of the
      specimens. Mutans streptococci (MS), non-mutans streptococci and total
      facultative bacteria were cultured. The plaque recovered from polyethylene FRC
      harboured significantly more MS than the plaque of ceramic, restorative composite
      and glass FRC. For the counts of non-mutans streptococci and total facultative
      bacteria, polyethylene FRC showed the highest counts, and ceramic showed a trend
      towards lower counts. The amount of plaque accumulation showed an association to
      the earlier reported surface roughness values of the studied materials. It was
      concluded that in the oral environment, polyethylene FRC promotes plaque
      accumulation and adhesion of MS more than glass FRC, restorative composite and
      dental ceramic. Glass FRC resembles restorative composite with respect to plaque
      accumulation and the adherence of MS.

PMID- 15988612
TI  - [Transparotidean approach to surgical management of condylar neck fractures. A
      prospective study].
AB  - AIM: Different surgical approaches for the open treatment of mandibular condylar
      fractures are described in the literature. We evaluated the morbidity of the
      transparotidean approach in a prospective study over 5 1/2 years. PATIENTS AND
      METHODS: A total of 48 patients with 52 condylar neck fractures class II and IV
      according to the Spiessl and Schroll classification were treated by a
      transparotidean approach. Rigid internal fixation was performed by means of
      miniplate fixation. After surgery, no mandibulomaxillary fixation was performed.
      The occurrence of surgical and functional complications was documented both
      during hospitalization and 1, 3, 6 and >9 months after surgery. RESULTS: In none
      of our patients were major problems in wound healing such as infection of the
      fracture site observed. At the beginning of the study, in four cases a fistula of
      the parotid gland was seen within the initial days after surgery; after careful
      wound closure of the parotid capsula in the following operations, no further
      complications involving fistulas were observed. Signs of temporary palsy of the
      facial nerve caused by the hooks occurred in ten (19.6%) of all patients but was
      completely reversible within the first 6 months after the procedure. One patient
      suffered temporarily from a minimal malocclusion and two patients from symptoms
      of the temporomandibular joint 6 months postoperatively. In three patients we
      observed miniplate fractures without consecutive dysfunction of the TMJ or
      malocclusion. CONCLUSION: Open reduction and rigid internal fixation of condylar
      neck fractures by transparotidean approach is a recommendable procedure in class
      II and IV fractures. With the advantages of minimal tissue alteration and rare
      complications on the one hand and sufficient exposure of the fracture site on the
      other hand, this technique has been established as a standard procedure in
      treating condylar neck fractures by open reduction.

PMID- 15988613
TI  - Looking at hydrocephalus: where are we now, where are we going?

PMID- 15988614
TI  - Jack Walker.

PMID- 15988615
TI  - Lipid peroxides, superoxide dismutase and circulating IL-8 and GCP-2 in patients
      with severe obstructive sleep apnea: a pilot study.
AB  - Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and
      mortality and many other physiological and immunological disorders. An increase
      in hypoxia due to OSA may cause generation of reactive oxygen species (ROS). ROS
      are toxic to biomembranes and may lead to peroxidation of lipids. An increase in
      systemic biomarkers of inflammation and oxidative stress has been found in
      patients with OSA. The first aim of this study was to test the hypothesis that
      OSA is linked to increased oxidative stress (lipid peroxidation) and decreased
      antioxidant defense [superoxide dismutase (SOD)]. The second aim was to measure
      the serum levels of neutrophil chemokines [interleukin-8 (IL-8)], and granulocyte
      chemotactic protein-2 (GCP-2) in OSA patients. Twenty five patients with severe
      OSA and 17 healthy subjects were recruited. IL-8 and GCP-2 were measured in the
      serum by a specific enzyme immunoassay kit. Oxidative stress level was
      quantitated by measurement of thiobarbituric acid reactive substances. SOD
      enzymatic activity was measured by purely chemical system based on NAD(P)H
      oxidation. Mean SOD and lipid peroxidation concentrations of patients were not
      significantly different from those of control subjects (0.29+/-0.015 vs 0.31+/
      0.01 U/ml and 4.64+/-0.57 vs 4.62+/-0.54 mmol/ml, respectively). Higher
      concentrations of IL-8 and GCP-2 were found in OSA patients (198.8+/-4.76 vs
      180.83+/-3.38 and 383.34+/-46.19 vs 218+/-13.16 pg/ml, respectively, p<0.005).
      The present study does not support the hypothesis that OSA is linked to increased
      oxidative stress and decreased antioxidant defense. On the other hand, it
      suggests that systemic inflammation characterizes OSA patients.

PMID- 15988616
TI  - Minimal activity in both proliferation and apoptosis of interstitial cells
      indicates seasonally persisting Leydig cell population in roe deer.
AB  - Seasonally regulated breeding is associated with significant changes in testis
      mass, structure and function. This includes the variation in size, structure and
      function of the Leydig cells. Recently, interstitial cells have been
      characterised as a numerically constant population in roe deer. However, no
      consistent data are available regarding changes in the number of Leydig cells,
      their differentiation or turnover in seasonally breeding mammals. This study has
      quantified the numbers of both proliferating and apoptotic cells in roe deer
      testis bimonthly during a complete annual cycle. Proliferation was detected by
      immunolocalisation of PCNA and Ki-67 in tissue sections, whereas apoptosis was
      localised by the TUNEL technique and an antibody to caspase-3. The labelled cells
      were counted by using a computer-aided image-analysing system. The number of
      proliferating spermatogenic cells per tubule cross section showed seasonal
      changes with a maximum in April (14.9+/-0.6) and a subsequent decline up to
      December (1.6+/-0.3). Percentages of positive cells per square millimetre of
      interstitial area were below 1% throughout the year. The average number of
      apoptotic cells per tubule cross section was low and varied only between 0.5 and
      1.4 (caspase-3) or 0.1 and 2.1 (TUNEL). In the interstitial compartment, only a
      few apoptotic cells (<or=0.7%) were found sporadically scattered within the
      intertubular region during all studied seasonal periods. The results suggest that
      a constant total number of interstitial cells arise from a conserved cell
      population of changing functional state rather than from a steady-state
      population with a definite turnover of cells during seasonal changes in
      testicular activity.

PMID- 15988617
TI  - Dexamethasone stimulates differentiation of odontoblast-like cells in human
      dental pulp cultures.
AB  - Regenerative dental pulp strategies require the identification of precursors able
      to differentiate into odontoblast-like cells that secrete reparative dentin after
      injury. Pericytes have the ability to give rise to osteoblasts, chondrocytes, and
      adipocytes, a feature that has led to the suggestion that odontoblast-like cells
      could derive from these perivascular cells. In order to gain new insights into
      this hypothesis, we investigated the effects of dexamethasone (Dex), a synthetic
      glucocorticoid employed to induce osteogenic differentiation in vitro, in a
      previously reported model of human dental pulp cultures containing pericytes as
      identified by their expression of smooth muscle actin (SMA) and their specific
      ultrastructural morphology. Our data indicated that Dex (10(-8) M) significantly
      inhibited cell proliferation and markedly reduced the proportion of SMA-positive
      cells. Conversely, Dex strongly stimulated alkaline phosphatase (ALP) activity
      and induced the expression of the transcript encoding the major odontoblastic
      marker, dentin sialophosphoprotein. Nevertheless, parathyroid hormone/parathyroid
      hormone-related peptide receptor, core-binding factor a1/osf 2, osteonectin, and
      lipoprotein lipase mRNA levels were not modified by Dex treatment. Dex also
      increased the proportion of cells expressing STRO-1, a marker of multipotential
      mesenchymal progenitor cells. These observations indicate that glucocorticoids
      regulate the commitment of progenitors derived from dental pulp cells to form
      odontoblast-like cells, while reducing the proportion of SMA-positive cells.
      These results provide new perspectives in deciphering the cellular and molecular
      mechanisms leading to reparative dentinogenesis.

PMID- 15988621
TI  - Ipsilateral breast tumor recurrence after breast-conserving therapy: A comparison
      of quadrantectomy versus lumpectomy at a single institution.
AB  - The aims of study were to compare the rates of ipsilateral breast tumor
      recurrence (IBTR), for patients treated with either quadrantectomy or lumpectomy
      at a single institution, and to identify predictors of IBTR after breast
      conserving therapy (BCT). The database and medical records of 807 patients who
      underwent BCT for breast cancer between 1987 and 2002 were reviewed. The age of
      the patient, tumor size, lymph node status, extensive intraductal component
      (EIC), re-excision, final margin status, and the extent of surgery were examined
      in reference to IBTR rates. Of the total 807 patients, 456 (56.5%) had undergone
      quadrantectomy and 351 patients (43.5%) had lumpectomy. Apart from the higher re
      excision rate in the lumpectomy group (p < 0.001), there were no significant
      differences in clinical and pathologic characteristics between the patients in
      the two groups. At the median follow-up time of 72 months, 28 cases of IBTR
      (3.4%) and 56 cases of systemic recurrence (6.9%) had developed in 72 patients
      (8.9%). On multivariate analysis, young age (< or =35) (p = 0.041), positive
      lymph node (p < 0.001), and the presence of EIC (p = 0.004) were independent
      predictors of IBTR. However, we could not find a significant difference in IBTR
      rate between the two groups (p = 0.546). Thus, the extent of breast surgery
      (quadrantectomy or lumpectomy) did not make a significant difference in IBTR if
      adequate surgical margins could be achieved.

PMID- 15988622
TI  - High hospital volume is associated with better outcomes for breast cancer
      surgery: analysis of 233,247 patients.
AB  - BACKGROUND: The relationship between hospital volume and outcomes needs to be
      further elucidated for low-risk procedures such as surgical therapy of localized
      breast cancer. The objective of this investigation was to assess the relationship
      between hospital volume and outcomes for breast cancer surgery. METHODS: A total
      of 233,247 patients who underwent breast-conserving therapy (BCT) and breast
      ablative therapy (BAT) for localized breast cancer were extracted from 13 years
      (1988-2000) of the Nationwide Inpatient Samples. Hospital volume was classified
      as low (<30 cases/year), intermediate (> or =30 to <70 cases/year), and high (>
      or =70 cases/year). Multiple linear and logistic regression analyses were used to
      assess the risk-adjusted association between hospital volume and outcomes.
      RESULTS: In risk-adjusted analyses, patients operated on at low-volume hospitals
      were 3.04 (p = 0.03) times more likely to die after BCT compared with patients
      operated on at high-volume hospitals. Similarly, low-volume hospitals had a
      significantly higher likelihood of postoperative complications (odds ratio [OR] =
      1.73, p = 0.01 for BCT; OR = 1.44, p < 0.001 for BAT) compared with high-volume
      hospitals. Compared with low-volume hospitals, length of hospital stay was
      significantly shorter and nonroutine patient discharge significantly lower for
      high-volume providers for both BCT and BAT (all p < 0.001). Patients were also
      significantly less likely to undergo BCT if operated on in a low- or intermediate
      volume hospital compared with a high-volume provider (p < 0.001). CONCLUSIONS:
      High-volume hospitals had significantly lower nonroutine patient discharge,
      postoperative morbidity and mortality, shorter length of hospital stay, and
      higher likelihood of performing BCT. Referral of patients with localized breast
      cancer to high-volume hospitals may be justified.

PMID- 15988623
TI  - Multimodal treatment of gastrointestinal tract tumors: consequences for surgery.
AB  - Formerly an exclusive business of surgery, gastrointestinal (GI) tumors are
      nowadays increasingly approached with multimodal strategies. Neoadjuvant concepts
      have had a particularly far-reaching impact on surgery and have contributed to
      improved survival. Modern pre-treatment staging and risk assessment provide the
      basis for decision on one of three general treatment concepts (1) Early cancers,
      confined to the mucosal/submucosal layers, are approached with primary surgery,
      without prior antineoplastic therapy. (2) Systemically metastasized tumors
      receive merely palliative treatment. (3) Locally advanced cancers are
      increasingly approached with neoadjuvant strategies. The benefit from these
      preoperative protocols is proven for diverse entities, but is evidently confined
      to a specific subgroup patients, i.e., the responders to neoadjuvant treatment.
      These are the ones benefiting most from subsequent surgical resection, which is
      required to ensure complete removal of the residual tumor tissue, as complete
      tumor regression occurs very rarely and cannot be proven without a specimen. The
      fact that responders will benefit and non-responders will not benefit or will
      even deteriorate during the neoadjuvant treatment makes early response prediction
      most demanding. An amazing new approach is the use of position emission
      tomography with fluro-desoxyglucose (FDG-PET) to assess the "metabolic response,"
      which is possible as early as 14 days after initiation of the neoadjuvant
      protocol. This strategy offers the chance for modulating the surgical approach in
      accord i.e., with such metrobolic response termination of the protocol and
      proceeding to resection in the case of nonresponse. The future of GI cancer
      surgery is multimodal therapy in a response-based fashion and requires reponse
      based trials for further evaluation.

PMID- 15988624
TI  - Rod and cone opsin families differ in spectral tuning domains but not signal
      transducing domains as judged by saturated evolutionary trace analysis.
AB  - The visual receptor of rods and cones is a covalent complex of the apoprotein,
      opsin, and the light-sensitive chromophore, 11-cis-retinal. This pigment must
      fulfill many functions including photoactivation, spectral tuning, signal
      transmission, inactivation, and chromophore regeneration. Rod and cone
      photoreceptors employ distinct families of opsins. Although it is well known that
      these opsin families provide unique ranges in spectral sensitivity, it is unclear
      whether the families have additional functional differences. In this study, we
      use evolutionary trace (ET) analysis of 188 vertebrate opsin sequences to
      identify functionally important sites in each opsin family. We demonstrate the
      following results. (1) The available vertebrate opsin sequences produce a
      definitive description of all five vertebrate opsin families. This is the first
      demonstration of sequence saturation prior to ET analysis, which we term
      saturated ET (SET). (2) The cone opsin classes have class-specific sites compared
      to the rod opsin class. These sites reside in the transmembrane region and tune
      the spectral sensitivity of each opsin class to its characteristic wavelength
      range. (3) The cytoplasmic loops, primarily responsible for signal transmission
      and inactivation, are essentially invariant in rod versus cone opsins. This
      indicates that the electrophysiological differences between rod and cone
      photoreceptors cannot be ascribed to differences in the protein interaction
      regions of the opsins. SET shows that chromophore binding and regeneration are
      the only aspects of opsin structure likely to have functionally significant
      differences between rods and cones, whereas excitatory and adaptational
      properties of the opsin families appear to be functionally invariant.

PMID- 15988625
TI  - Image quality assurance of soft copy display systems.
AB  - Image quality assurance has traditionally been a high priority in medical imaging
      departments. Recently, it has often been neglected with the transition from hard
      copy (film) to soft copy (computer) display systems, which could potentially
      result in difficulty in reading images or even misdiagnosis. This transition
      therefore requires careful management such that comparable image quality is
      achieved at a minimum. It is particularly difficult to maintain appropriate image
      quality in the clinical settings outside of medical imaging departments because
      of the volume of display systems and the financial restraints that prohibit the
      widespread use of dedicated computers and high-quality monitors. In this study, a
      protocol to test and calibrate display systems was developed and validated by
      using an inexpensive calibration tool. Using this protocol, monitors were
      identified in a hospital in which image quality was found to be inadequate for
      medical image viewing. It was also found that most monitors could achieve a
      substantial increase in image quality after calibration. For example, the 0 and
      5% luminance difference was discernable on 30% of the piloted display systems
      before calibration, but it was discernable on 100% post calibration. In addition,
      about 50% of the piloted display systems did not have the maximum luminance
      (white level) suitably set, and 35% of them did not have the minimum luminance
      (dark level) suitably set. The results indicate that medical display systems must
      be carefully selected and strictly monitored, maintained, and calibrated to
      ensure adequate image quality.

PMID- 15988626
TI  - General consumer communication tools for improved image management and
      communication in medicine.
AB  - We elected to explore new technologies emerging on the general consumer market
      that can improve and facilitate image and data communication in medical and
      clinical environment. These new technologies developed for communication and
      storage of data can improve the user convenience and facilitate the communication
      and transport of images and related data beyond the usual limits and restrictions
      of a traditional picture archiving and communication systems (PACS) network. We
      specifically tested and implemented three new technologies provided on Apple
      computer platforms. (1) We adopted the iPod, a MP3 portable player with a hard
      disk storage, to easily and quickly move large number of DICOM images. (2) We
      adopted iChat, a videoconference and instant-messaging software, to transmit
      DICOM images in real time to a distant computer for conferencing teleradiology.
      (3) Finally, we developed a direct secure interface to use the iDisk service, a
      file-sharing service based on the WebDAV technology, to send and share DICOM
      files between distant computers. These three technologies were integrated in a
      new open-source image navigation and display software called OsiriX allowing for
      manipulation and communication of multimodality and multidimensional DICOM image
      data sets. This software is freely available as an open-source project at
      http://homepage.mac.com/rossetantoine/OsiriX. Our experience showed that the
      implementation of these technologies allowed us to significantly enhance the
      existing PACS with valuable new features without any additional investment or the
      need for complex extensions of our infrastructure. The added features such as
      teleradiology, secure and convenient image and data communication, and the use of
      external data storage services open the gate to a much broader extension of our
      imaging infrastructure to the outside world.

PMID- 15988627
TI  - Benefits of the DICOM modality performed procedure step.
AB  - A few years ago, the Digital Imaging and Communications in Medicine standard
      introduced a network transaction that is initiated by modality equipment, mainly
      at the beginning and at the end of the acquisition. This transaction, the
      Modality Performed Procedure Step (MPPS), is sent to the Picture Archiving and
      Communication System and/or to the Radiology Information System. It carries
      information about what really has been performed by the modality equipment during
      acquisition. In this paper, we present MPPS and discuss its benefits. We show how
      MPPS enables efficient radiology workflow and how it ensures accuracy and
      completeness of imaging information. We think our paper helps bridge the gap
      between MPPS implementation and deployment. By understanding all the MPPS
      benefits, the end user becomes aware of the great enhancement in patient care
      that this transaction provides.

PMID- 15988628
TI  - Joint toxicity of triazine herbicides and organophosphate insecticides to the
      midge Chironomus tentans.
AB  - A series of recent studies demonstrated that the triazine herbicide atrazine,
      although not itself acutely toxic, potentiated the toxicity of certain
      organophosphate insecticides (OPs) to the midge Chironomus tentans. In the
      current study, a series of triazine herbicides and triazine herbicide degradation
      products were tested to determine if other triazines potentiate OP toxicity to
      midges. Chlorpyrifos and diazinon were the OPs tested. Toxicity tests were
      conducted using a factorial design and analysis of variance to statistically
      determine if each triazine had an effect on expected toxicity. Log-probit
      procedures were also used to evaluate the magnitude of change in median effective
      concentration (EC50) values during coexposure with each triazine. All of the
      triazine herbicides tested (atrazine, simazine, cyanazine, and hexazinone) were
      capable of potentiating the toxicity of the OPs, whereas the degradation products
      (s-triazine, deethylatrazine, and deisopropylatrazine) had less effect. In most
      cases, a triazine concentration of 100 microg/L was necessary to significantly
      increase OP toxicity, and higher concentrations of triazine caused a greater
      degree of potentiation. Changes in EC50 values ranged from no change to a 2.5
      fold increase in toxicity. Generally, EC50 values changed by less than a factor
      of 2, indicating that the effect may be of limited concern in regard to future
      risk assessments of OPs.

PMID- 15988629
TI  - Exocellular peptides from Antarctic psychrophile Pseudoalteromonas Haloplanktis.
AB  - A novel diketopiperazine, named cyclo-(D-pipecolinyl-L-isoleucine) (DKP 1), and 7
      known diketopiperazines were isolated from the cell-free culture supernatant of
      the Antarctic psychrophilic bacterium Pseudoalteromonas haloplanktis TAC125. Two
      diketopiperazines containing pipecolinyl moiety were isolated for the first time
      from a natural source. Two new linear peptides, stable to bacterial proteolytic
      enzymes, were also characterized. The structures of the isolated compounds were
      elucidated by means of spectroscopic data (1D-, 2D-NMR, EIMS, FABMS, and
      ESIMS/MS) and chiral high-performance liquid chromatography. The potential
      antioxidant activity of the isolated compounds was evaluated by a DPPH free
      radical scavenging assay.

PMID- 15988630
TI  - Development of panel of monoclonal antibodies specific to urochordate cell
      surface antigens.
AB  - Monoclonal antibodies are an important tool in the study of botryllid ascidians'
      immunology and developmental biology. Here we describe the development of a panel
      of 38 monoclonal antibodies that are specific to Botryllus schlosseri
      (Ascidiacea; subfamily Botryllinae) cell surface antigens. Many of these
      hybridomas recognize (by enzyme-linked immunosorbent assay and
      immunohistochemistry) epitopes of Botrylloides subpopulations (SP) II and III
      from the Mediterranean coast of Israel and show, on blood cell smear assays,
      reactions with subsets of Botryllus circulating blood cells. Fluorescence
      activated cell sorting analyses using antibodies positive for botryllid tissues
      revealed up to 3.6% positive cells. ELISA screenings were performed with 64 new
      monoclonal antibodies on 5 different individual botryllid ascidian colonies (B.
      schlosseri, Botrylloides). The positive antibodies in this panel identified a
      large number of different antigenic determinants, some of which distinguish
      Botryllus versus Botrylloides colonies, and other, different colonies within
      these two species, or different cell types within tissues, embryos, and buds of
      individual colonies. Only 21 monoclonal antibodies tested positive with all
      colonies. Cross-reactivity with at least one Botrylloides colony was recorded in
      49 hybridomas that identified Botryllus cells. This wide panel of monoclonal
      antibodies is the first such detailed set of monoclonals available for studies on
      botryllid ascidians.

PMID- 15988631
TI  - Attitudes and knowledge about pain: an assessment of West Virginia family
      physicians.
AB  - BACKGROUND AND OBJECTIVES: This study's objective was to determine the
      attitudes/beliefs and knowledge of West Virginia's family physicians regarding
      evaluation and treatment of patients with pain. METHODS: A 20-item instrument (10
      attitudinal/behavioral and 10 knowledge items) was mailed to 537 members of the
      West Virginia Chapter of the American Academy of Family Physicians in October
      2002. Five percent of the surveys were mailed to out-of-state members. No follow
      up questionnaire was mailed. RESULTS: A total of 186 surveys (186/537, 34.6%)
      were returned. The typical respondent was a male ages 30-54 graduating in 1983 or
      later and having 15.5 years of practice experience. The majority of respondents
      were in a solo or group practice. There were no differences in response rates
      according to age, gender, years in practice, and practice setting. Chronic
      nonmalignant pain and assessing pain in the elderly are problematic for many
      physician providers. Perceived regulatory scrutiny does impact physician
      prescribing of opioids for patients in pain. Knowledge gaps were uncovered in the
      areas of fentanyl administration, the use of propoxyphene in the elderly, the
      management of opioid-induced constipation, laxative prescription, and the use of
      oxygen to manage opioid-induced respiratory depression. The majority of
      respondents felt that their formal medical training did not prepare them to
      effectively manage pain. CONCLUSIONS: This survey provides valuable insight into
      the attitudes/behaviors and knowledge about pain and its management by West
      Virginia family physicians. A national sample, using a revised instrument, is
      needed to more fully characterize and validate the findings from this statewide
      survey.

PMID- 15988632
TI  - Elder abuse and neglect: the experience, knowledge, and attitudes of primary care
      physicians.
AB  - BACKGROUND AND OBJECTIVES: Two million elderly Americans are abused or neglected
      each year. Elderly patients visit their physicians approximately five times each
      year. Yet physicians initiate only about 2% of the reported cases of abuse and
      neglect. This study's purpose was to assess the experience, knowledge, and
      attitudes of primary care physicians toward elder mistreatment. METHODS: A self
      report questionnaire was mailed to a random sample of 500 primary care
      physicians. The population included 250 family physicians and 250 general
      internists in Ohio, divided equally between large urban, suburban, and rural
      practice settings. RESULTS: The overall response rate was 78%, with 216 family
      physicians and 176 internists responding. Nearly 72% of those responding reported
      no exposure or only minimal exposure to the physical, emotional, or sexual abuse
      of the elderly. More than half of the respondents in both groups reported that
      they had never identified a case of elder mistreatment. Both family physicians
      and general internists estimated its prevalence as roughly less than 25% of the
      prevalence documented in the medical literature, and both were reluctant to
      accept the problem as universal. More than 60% of clinicians in both groups
      indicated they had never asked their elderly patients about abuse. Family
      physicians tended to have a better knowledge of those elements encompassing elder
      mistreatment and were more aware of management options. CONCLUSIONS: Physicians
      need more education about elder mistreatment.

PMID- 15988633
TI  - Family medicine residents do not ask better-formulated clinical questions as they
      advance in their training.
AB  - OBJECTIVE: We investigated whether family medicine residents demonstrated
      increased skill in formulating clinical questions over their 3 years of training.
      METHODS: We conducted an analysis of 454 questions asked by 49 family physician
      residents engaged in informal consultation with subspecialists using an e-mail
      based system. Clinical question formulation was measured on a scale of 0 to 2 by
      awarding 1 point each for the presence of a proposed intervention and a desired
      outcome. Changes in question formulation as residents progressed in their
      training were assessed using cross-sectional and repeated measures. FINDINGS: The
      mean question quality was scored at 1.10, and there was no significant change
      over the 3 years. Thirteen residents used the e-mail service over their entire 3
      year training period. The individual residents showed substantial differences in
      how well they formulated clinical questions, with their mean question quality
      scores ranging from 0.38 to 1.45. There was, however, no evidence that the
      quality of their questions changed as they progressed in their medical training.
      CONCLUSIONS: Resident physicians asked moderately well-formulated clinical
      questions, but question formulation did not improve as they progressed in
      clinical training. Further training in formulating clinical questions may be
      helpful.

PMID- 15988634
TI  - Where Canadian family physicians learn procedural skills.
AB  - BACKGROUND AND OBJECTIVES: Little is known about where family physicians learn
      procedural skills. In this study, we examine where Canadian family medicine
      graduates learned to do the procedures they perform. METHODS: In 2001, a cross
      sectional postal survey was conducted of the 369 family medicine graduates from
      the University of Alberta and the University of Calgary between 1996 - 2000. From
      a list of 31 procedures, respondents identified procedures regularly performed
      over the past 2 years and indicated which procedures they had stopped performing.
      Respondents indicated whether the procedures performed were learned primarily
      during medical school and residency, through formal skills training following
      residency, or in the practice setting. RESULTS: The 282 (76.4% response rate)
      respondents reported performing a mean of 10.5 (SD=5.3) procedures. The vast
      majority reported learning procedural skills in medical school or during family
      medicine residency training (91.1%), followed by the clinical practice setting
      (12.6%), then formal skills training (6.4%). Those in rural practice learned a
      relatively greater proportion of procedural skills through formal skills
      training. CONCLUSIONS: For Canadian family physicians, procedural skill
      acquisition occurs across the learning continuum. Medical schools and residency
      training programs play a role in facilitating the learning of procedural skills
      and supporting self-directed learning.

PMID- 15988635
TI  - Residency recruitment and NRMP success.

PMID- 15988636
TI  - The effects of shortening residency training.

PMID- 15988637
TI  - The increasing rate of repeat cesarean section at a community FM residency
      program.

PMID- 15988638
TI  - Orienting family medicine residents and medical students to office practice.

PMID- 15988639
TI  - Teaching cervical dilation measurement to family medicine residents.
AB  - BACKGROUND AND OBJECTIVES: Cervical dilation measurement is difficult to teach.
      This pilot study's objective was to determine if residents participating in an
      innovative workshop improved their cervical measurement accuracy when using soft
      cervical models in the classroom. METHODS: Resident physicians measured cervical
      models before and after the workshop. We compared pre-workshop and post-workshop
      coefficients of variation using a standard t test. CONCLUSION: Residents reduced
      their measurement error from 38.2% to 15.6%.

PMID- 15988640
TI  - Report and reflections on a day working in the fields.

PMID- 15988641
TI  - Literature and medical interventions: an experiential course for undergraduates.

PMID- 15988642
TI  - Functional fitness: maintaining or improving function for elders with chronic
      diseases.
AB  - OBJECTIVE: This study's objective was to prove or disprove four hypotheses, three
      addressing physical function and a subjective measure of self-perceived well
      being from participating in an elder functional fitness program. METHODS:
      Participants included 17 chronically ill residents from an assisted-living center
      in Maine. Measures on mobility, metabolic equivalent estimation (MET) levels,
      resting heart rate, blood pressure, oxygen saturation, muscular strength,
      flexibility, and body weight were conducted at three intervals-baseline, 6
      months, and 1 year. SAS software was used for analysis of means and paired t
      test. RESULTS: Increases in or maintenance of function proved significant. The
      subjective hypothesis also proved significant. DISCUSSION: Research on elder
      exercise focuses on one or two components, rather than the benefits of a thorough
      fitness program. This study illustrated improvements in physical function and
      well-being from participating in a comprehensive elder fitness program.

PMID- 15988643
TI  - A short transitional course can help medical students prepare for clinical
      learning.
AB  - BACKGROUND AND OBJECTIVES: Despite the move toward integrated 4-year medical
      school curricula, many medical schools still offer a "2+2" curriculum divided
      into preclinical and clinical phases. These phases represent distinct learning
      environments that require different learning skills. To prepare students for
      learning in the clinical environment of the second 2 years, many medical schools
      offer transitional experiences before the third-year clerkships. Few of these
      transitional courses have published evaluations, and there is no consensus on the
      ideal content. In this paper, we provide evaluation and content validity data on
      a 2-week intensive clinical transition course for beginning third-year medical
      students. METHODS: A multidisciplinary team designed, implemented, and evaluated
      a 2-week transition course. Students indicated through surveys how prepared they
      felt for 18 clinical skills. We analyzed pre- and post-survey data using a
      Wilcoxen rank sum test and compared current to prior students using a chi-square
      analysis. RESULTS: Students felt more prepared for 16 of 18 skills after the
      transitional course and for 14 of 18 skills compared to historical controls.
      CONCLUSIONS: A transitional course based on common skills is relevant to
      students' clerkship experiences and can increase students' self-reported
      preparedness for the clinical years of medical school.

PMID- 15988644
TI  - Family medicine in Iran: the birth of a new specialty.
AB  - Since the revolution of 1978-1979, the government of Iran has worked toward
      development of a primary health care system to improve basic health for its
      citizens. Although infant mortality and other parameters have improved,
      increasing urbanization and poor lifestyle choices continue to present major
      challenges to improving overall health statistics in the country. Generalist
      physicians, with no training beyond medical school graduation, have not inspired
      confidence from patients or specialist colleagues. Therefore, many patients
      prefer to receive care for common health complaints from specialist physicians.
      Health care for many individuals tends to be episodic, driven by patient concerns
      for acute illness rather than by patient-centered, longitudinal care. The
      government of Iran has decided to develop family medicine as a specialty within
      the country to help respond to these problems. Based on an initial consultation
      with some leaders in the Ministry of Health and Medical Education, as well as
      students, nursing staff, subspecialists, administrators, and medical educators, a
      number of suggested steps were recommended to support the development of family
      medicine in Iran. These involved, among others, further development of the
      specialty and parity with other specialties, development of faculty and
      curricula, and a plan for financing rural health care.

PMID- 15988645
TI  - Prostate cancer and sexually transmitted diseases: a meta-analysis.
AB  - BACKGROUND: Prostate cancer is the most common neoplasm of American men and the
      second most common cause of cancer-related deaths. Research suggests that
      infection and subsequent inflammation may be an important risk factor in the
      pathogenesis of prostate cancer. In this meta-analysis, we examine the current
      epidemiological evidence for the association between specific sexually
      transmitted diseases (STDs) and prostate cancer. METHODS: Using an English
      language search of Medline and CINAHL (Cumulative Index to Nursing and Allied
      Health) since 1966, 29 case-control studies were identified. These studies
      included a total of 6,022 cases of prostate cancer and 7,320 controls. Using
      Review Manager, combined odds ratios (ORs) were calculated for any STDs,
      gonorrhea, syphilis, and human papillomavirus (HPV) for prostate cancer. RESULTS:
      Significant elevated ORs for prostate cancer were demonstrated for any STDs
      (1.48, 95% confidence interval [CI] 1.26-1.73), gonorrhea (1.35, 95% CI 1.05
      1.83), and human papillomavirus (1.39, 95% CI 1.12-2.06). CONCLUSIONS: This meta
      analysis provides evidence of a higher rate of prostate cancer in men with a
      history of an exposure to gonorrhea, HPV, or any STD. Further research,
      especially with cohort studies, is required to confirm this potentially
      modifiable risk factor.

PMID- 15988646
TI  - The end of the beginning: the redesign imperative in family medicine.

PMID- 15988650
TI  - Anatomy of the jawline, neck, and perioral area with clinical correlations.
AB  - The dramatic rise in the number of cosmetic procedures performed during the past
      5 years reflects a heightened public awareness of and interest in facial
      rejuvenation. Concomitant with this rise has been the addition of new injectable
      fillers, lasers, and minimal incision techniques to the surgeon's armamentarium.
      Perhaps the greatest applicability of these modalities has been the rejuvenation
      of the perioral region, neck, and jawline, with reduced "downtime" but visible
      results. Signs of aging that are clearly visible in the lower third of the face
      include the loss of elasticity and descent of fat in the jowl region; laxity of
      the neck skin, muscle, and fat; development of perioral rhytids, deep nasolabial
      folds, and marionette lines; and the loss of definition of the lips. The purpose
      of this article is to highlight our approach to rejuvenation of these areas,
      elucidate the role of newer technologies, and provide special techniques and
      pearls utilized in rhytidectomy.

PMID- 15988651
TI  - Surgical management of the aging neck.
AB  - Blunting of the cervicomental angle with age is caused by progressive laxity of
      the skin and subcutaneous tissues, along with proliferation of fatty deposits and
      platysma muscle banding. This contributes to a loss of the slender neckline
      associated with youth, often a primary point of concern for patients. Surgeons
      may avail themselves of several surgical techniques in common use to restore
      definition to this region. A thorough evaluation of bone and soft tissue anatomy
      informs the appropriate surgical approach and allows successful rejuvenation of
      the aging neck. The lead author's tactics for enhancement of the neck are
      outlined.

PMID- 15988652
TI  - Minimal incision facelift.
AB  - Many procedures have been developed in an attempt to improve facial ptosis. These
      have ranged from subcutaneous dissections with skin excision to deeper
      dissections focused on supporting the superficial musculoaponeurotic system and
      even the periosteal layer. These deeper dissections, although theoretically
      giving better and longer lasting results, also carry an increased risk of
      complications. This article describes a new facelift technique that minimizes
      complications while maximizing cosmetic results (especially in the neck and jowl
      areas) and patients' comfort and satisfaction. Aesthetic results (as determined
      by pre- and postoperative photographs) and complications of 35 consecutive
      patients undergoing both traditional rhytidectomy and minimal incision facelift
      are compared. The minimal incision facelift technique has shown improved cosmetic
      results and a decreased complication rate compared with traditional rhytidectomy
      and is a safe and very effective technique for the treatment of facial ptosis.

PMID- 15988653
TI  - Restoration of the jawline and the neck after bariatric surgery.
AB  - Bariatric surgery can result in massive, rapid weight loss. Patients who undergo
      this surgery can be left with significant facial and neck skin redundancy and may
      request restorative facial plastic surgery. Optimal results require a thorough
      understanding of the unique physiologic, metabolic, and anatomic findings in
      these patients. Modifications of standard rhytidectomy techniques are necessary
      to suit the specific features of the patient after bariatric surgery.

PMID- 15988654
TI  - Effects of subperiosteal midfacial elevation via an endoscopic brow-lift incision
      on lower facial rejuvenation.
AB  - Many techniques have been developed for rejuvenation of the midface. This article
      describes the technique of subperiosteal midface elevation via an endoscopic brow
      incision approach developed by the senior author and reviews the results of this
      technique, with specific emphasis upon the effect on lower facial rejuvenation.

PMID- 15988655
TI  - Chin and prejowl augmentation in the management of the aging jawline.
AB  - The effects of aging in the lower face and neck are reflected in the contour of
      the jawline. Soft tissue atrophy, the formation of jowls, and retrusion of the
      chin are all age-associated changes that contrast starkly with the smooth harmony
      of a young lower face. These soft tissue changes in the jawline are exacerbated
      by the effects of aging on the bony portion of the mandible. Bone resorption of
      the mandible seen with aging can lead to the development of a hypoplastic mentum
      and the formation of an anterior mandibular groove. Rhytidectomy serves to
      address the soft tissue changes from aging but cannot counter the effects of
      aging on the bony mandible itself. Understanding the effects of bone resorption
      on the aging mandible allows the facial plastic surgeon to augment the mandible
      appropriately to achieve a more effective rejuvenation of the lower face. The
      aging process in the mandible and the development of the prejowl sulcus are
      reviewed. The use of chin and prejowl augmentation as a valuable adjuvant to
      facelift surgery is discussed.

PMID- 15988656
TI  - Alternative management of the aging jawline and neck.
AB  - The lower third of the face and neck have distinct changes that occur with aging.
      These changes can be globally and dramatically addressed with a traditional
      rhytidectomy. However, as the demographics of facial plastic surgery patients
      evolve, patients seek increasingly less invasive procedures that will result in
      faster recovery time and less postoperative morbidity. To accommodate this
      change, today's facial plastic surgeon must include less invasive procedures in
      the treatment strategies for the lower face and neck. Correct, patient-specific
      procedure selection and patient education can yield results similar to those of a
      traditional facelift. This article discusses options available for treatment of
      the lower face and neck.

PMID- 15988657
TI  - The functional anatomy of the lower face as it applies to rejuvenation via
      chemodenervation.
AB  - Botulinum toxin type A (Botox) injections have revolutionized nonsurgical
      rejuvenation of the upper face since their introduction in the early 1990s. Their
      use in the lower face has not become nearly as popular. The key to using Botox to
      improve the appearance of the lower face lies in understanding the functional
      anatomy of the lower face musculature. Although the facial plastic surgeon should
      be familiar with the muscles of the lower face and anatomic variations, the
      functional anatomy of the lower face varies widely from patient to patient and
      even more from one side of the face to the other. Understanding how the lower
      face moves is the key to using Botox to improve nasolabial folds, perioral
      rhytids, chin dimpling, marionette's lines, and downturned oral commissures. This
      is not an area for the novice injector, as a few stray units are not tolerated
      nearly so well as they are in the upper face.

PMID- 15988658
TI  - Current concepts in nonablative radiofrequency rejuvenation of the lower face and
      neck.
AB  - With the multitude of treatment options and emerging technology available for
      rejuvenation of the lower face and neck, it is often difficult to determine which
      specific treatment would benefit an individual patient. Monopolar radiofrequency
      (MRF) nonablative skin rejuvenation is a promising new procedure that is utilized
      to tighten and contour nonsurgically mild to moderate laxity of the skin of the
      lower face and neck in patients without significant underlying structural ptosis.
      In these selected patients and others who wish to avoid surgical treatment
      modalities, MRF treatment offers a noninvasive method of tightening skin and soft
      tissue, causing softening of the nasolabial lines, tightening of the jowl, and
      improving the definition of the cervicomental angle, all without significant
      recovery time or complications. Further development of MRF technology and
      refinement of treatment protocols may allow even greater tightening of the skin
      and more dramatic modulation of underlying deeper structures, making the
      treatment more universally applicable for patients desiring facial rejuvenation.

PMID- 15988659
TI  - Soft tissue fillers for management of the aging perioral complex.
AB  - Rejuvenative therapy of the lower face has traditionally been surgical in nature,
      with office-based treatments such as soft tissue fillers relegated to "second
      tier" status. However, traditional rhytidectomy does not significantly affect the
      perioral complex and leaves the central lower face unaltered and unimproved. If
      it is left untreated, there is a clear disparity between the rejuvenated neck and
      aged perioral area. Soft tissue augmentation of the perioral area can provide
      rapid aesthetic improvement. Careful analysis of this area and appropriate
      treatment can harmonize these areas and produce a globally aesthetic result.

PMID- 15988660
TI  - [Diagnosis and treatment of acute pancreatitis: are the guidelines accepted?].
AB  - BACKGROUND AND OBJECTIVE: Eight international guidelines exist for the diagnosis
      and treatment of acute pancreatitis, a disease that is often difficult to assess
      and treat, particularly when the necrotising variety of the disease is present.
      The knowledge of and compliance with these guidelines in Germany is unknown.
      METHOD: In order to assess the knowledge and compliance with acute pancreatitis
      guidelines, a structured questionnaire was sent out to the 190 members of the
      ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausarzte), a
      professional organisation of gastroenterology chairmen, who, in their respective
      institutions, are responsible for the diagnosis and treatment of acute
      pancreatitis. University hospitals were excluded to cover the entire severity
      spectrum of the disease and to avoid a referral bias. RESULTS: The questionnaire
      was responded by 182 (96 %) members. To a large extent (acceptance > 2/3 of the
      consultants), guideline recommendations were complied with. There was,
      nevertheless, disagreement regarding the prophylactic use of antibiotics
      (acceptance < 2/3 of the consultants), as to when a contrast-enhanced computed
      tomography was indicated, and the timing of cholecystectomy for biliary
      pancreatitis. The choice of pain therapy for patients with acute pancreatitis
      also remained equivocal. CONCLUSION: Based on the high response rate which
      excludes a non-responder bias, the results of our study reflect the current
      status of the diagnosis and therapy of acute pancreatitis in Germany and to what
      extent international guidelines are known and complied with. This study also
      highlights the need for additional clinical trials in areas of diagnostic or
      therapeutic uncertainty.

PMID- 15988661
TI  - [Complications and diagnostic limitations of chronic meningitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 37-year-old woman was admitted with total loss
      of vision of the left eye within 24 hours. Additionally, she complained about
      fatigue, headache, chills, fever, muscle pain and neck stiffness since 4 days. At
      admission, the body temperature was 38.7 degrees C. Neurological examination
      revealed papilledema and meningism. INVESTIGATIONS: Ophthalmologic findings were
      consistent with a papillitis. The vision was lost, the pattern-shift checkerboard
      visual evoked potentials were not measurable. MRI of the brain and the optical
      nerve was without pathological findings, meningeal or cerebral Gadolinium
      enhancement was not present. The CSF analysis yielded a lymphocytic meningitis
      with 249 cells/mm (3), the glucose ratio of cerebrospinal fluid and serum was
      normal. DIAGNOSIS, TREATMENT AND COURSE: The papillitis was treated
      unsuccessfully with high-dose methylprednisolone, the left eye remained blind.
      Persistence of the pleocytosis under initial treatment with aciclovir and
      ceftriaxone, reduction of the glucose ratio of cerebrospinal fluid and serum and
      intrathecal immunoglobuline A -- synthesis required a change of the diagnostic
      and therapeutic regimen. Various common and rare differential diagnoses were
      considered and ruled out, a chronic meningitis of unclear aetiology with the
      complication of amaurosis was diagnosed. In consideration of the most probable
      diagnosis, a tuberculostatic therapy was initiated. A prolonged reduction of the
      pleocytosis and normalization of cerebrospinal fluid parameters could be
      observed. CONCLUSIONS: A large number of aetiologies can cause chronic
      meningitis; this case report reviews the most important differential diagnoses
      and highlights the limitations of the diagnostic work-up although various methods
      are available. Clinical course and symptoms of chronic meningitis are mild to
      moderate and may even be absent, but it can cause severe complications.

PMID- 15988662
TI  - [Hamartoma of the duodenum].
AB  - HISTORY AND ADMISSION FINDINGS: A 61-year-old man had been suffering from
      repeated episodes of postprandial vomiting and a feeling of fullness as well as a
      weight loss of 8 kg for two months. Three years prior to this, a laparoscopic
      cholecystectomy had been carried out at a different institution after a
      pancreatitis on the assumption of a biliary genesis. There were no sings of
      jaundice or gastro-intestinal bleeding. The physical examination was -- apart
      from epigastric pain -- unremarkable. INVESTIGATIONS: The routine laboratory
      parameters and tumor markers were within normal range. Endoscopy revealed a
      thickened duodenal wall with a stenosis at the level of the papilla, and a
      tumorous mass in the duodenal bulb. The biopsy specimens gave no evidence of
      malignancy. The barium upper GI series revealed an excentric stenosis of the
      duodenal pars II. Computerized tomography showed no evidence for tumor growth
      extending beyond the wall or a pathologic enlargement of the adjacent lymph
      nodes. THERAPY AND COURSE: A pylorus-preserving partial duodenopancreatectomy was
      performed and the postoperative course was without any complications. The
      histological examination of the resectate showed -- besides a chronically
      fibrosing pancreatitis -- a hamartoma of the duodenal wall. CONCLUSION: Besides
      the endoscopic removal of a hamartoma of the duodenum a surgical transduodenal
      resection represents the most frequently applied procedure. The partial
      duodenopancreatectomy is a rather rare therapeutic option. It was chosen in our
      patient on account of the atypical presentation of the tumor, unclear histology
      and an adequate operative risk.

PMID- 15988664
TI  - [Pulmonary embolism -- actual diagnostics].

PMID- 15988665
TI  - [Medical assessment of fitness for detention in police custody].

PMID- 15988666
TI  - [Ethics and diagnosis related groups].
AB  - At the turn of the year 2003/2004 a change took place in the in-patient sector of
      the German public health care system from the former daily-rate-based
      reimbursement of medical services to a reimbursement in accordance with diagnosis
      related groups (DRGs). At the same time, there are indications for a paradigm
      change in the allocation of medical services: away from the even provision of
      medical care across all country's municipalities towards a concentration in
      specialized medical centres - with uncertain ethical implications. On one hand,
      one hopes to cut costs in the in-patient area. On the other hand, it is
      questionable, whether cutting costs still allows an adequate treatment of
      multimorbid, chronically ill patients. The new system likely favours the active,
      autonomously deciding patient, who is capable of using additional information
      from the planned quality reports to obtain the best possible medical services.
      But the new system could create a disadvantage for the less informed patient
      groups, especially those who don't have easy access to such information. It is
      not our intention to idealise the German health care system before the invention
      of diagnosis related groups. Based on a survey of studies from the U.S., the
      article assesses consequences of such a system and relates them to ethical
      considerations.

PMID- 15988667
TI  - [Information to patients on risks and adverse effects of medications. Decision on
      patients' rights of Mar 14 005].

PMID- 15988668
TI  - [Is patient care planning applicable for physicians?].

PMID- 15988669
TI  - [Evidence-based medicine and real-world studies using diabetes mellitus as an
      example].

PMID- 15988670
TI  - [Epidemiology and costs of diabetes mellitus in Germany].

PMID- 15988671
TI  - [Definition, procedures and goals of evidence-based medicine].

PMID- 15988672
TI  - [Expectations of the bearer of the cost of clinical studies and transformation to
      care by physicians under contract].

PMID- 15988673
TI  - [Real-world studies for answering real-world questions].

PMID- 15988674
TI  - [Experiences with the realisation of innovative study designs using the example
      of the HOPE-study].

PMID- 15988675
TI  - [Retrolective study design -- a new tool of evidence-based medicine].

PMID- 15988676
TI  - [Performance of real-world studies for inhaled insulin].

PMID- 15988679
TI  - Screening for non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality and is usually discovered at
      an advanced stage, when treatment is generally not effective. Many researchers
      have investigated the value of screening for lung cancer, which would
      theoretically allow earlier detection and more effective treatment.
      Unfortunately, no trials of screening strategies for lung cancer have shown a
      mortality benefit, and as a result, no major medical organization currently
      recommends screening. Research continues to seek proof of the benefit of
      screening as new techniques are developed, including low-dose spiral computed
      tomography (CT), autofluorescence bronchoscopy, and advanced techniques of sputum
      analysis. Although there are promising data on the sensitivity of these newer
      screening methods, especially low-dose CT, for detecting early lung cancer, none
      of the published trials are controlled, and they have not yet proven a decrease
      in mortality. There are ongoing randomized, controlled trials aiming to
      demonstrate a mortality benefit. Patients who are interested in being screened
      for lung cancer should be encouraged to participate in well-designed clinical
      trials whenever possible.

PMID- 15988680
TI  - Novel strategies for the early detection and prevention of lung cancer.
AB  - Lung cancer is the leading cause of cancer death in the United States. Despite
      evidence of molecular abnormalities in biological specimens, progress in this
      disease is hampered by the lack of diagnostic markers useful for clinical
      practice. The majority of patients with lung cancer are still diagnosed at an
      advanced stage, when prognosis is poor. This article reviews new strategies being
      studied for the early detection of lung cancer. These strategies involve new
      methods of imaging (including low-dose computed tomography [CT] scanning), DNA
      analysis, and proteomic-based techniques. These strategies have not only improved
      our understanding of lung cancer but show promise in offering better survival to
      patients with this deadly disease. Of paramount importance in the search for
      methods of early detection is the need for the identification of the ideal
      population to screen, a multidisciplinary approach, and validation of promising
      techniques.

PMID- 15988677
TI  - A combined genomewide linkage scan of 1,233 families for prostate cancer
      susceptibility genes conducted by the international consortium for prostate
      cancer genetics.
AB  - Evidence of the existence of major prostate cancer (PC)-susceptibility genes has
      been provided by multiple segregation analyses. Although genomewide screens have
      been performed in over a dozen independent studies, few chromosomal regions have
      been consistently identified as regions of interest. One of the major
      difficulties is genetic heterogeneity, possibly due to multiple, incompletely
      penetrant PC-susceptibility genes. In this study, we explored two approaches to
      overcome this difficulty, in an analysis of a large number of families with PC in
      the International Consortium for Prostate Cancer Genetics (ICPCG). One approach
      was to combine linkage data from a total of 1,233 families to increase the
      statistical power for detecting linkage. Using parametric (dominant and
      recessive) and nonparametric analyses, we identified five regions with
      "suggestive" linkage (LOD score >1.86): 5q12, 8p21, 15q11, 17q21, and 22q12. The
      second approach was to focus on subsets of families that are more likely to
      segregate highly penetrant mutations, including families with large numbers of
      affected individuals or early age at diagnosis. Stronger evidence of linkage in
      several regions was identified, including a "significant" linkage at 22q12, with
      a LOD score of 3.57, and five suggestive linkages (1q25, 8q13, 13q14, 16p13, and
      17q21) in 269 families with at least five affected members. In addition, four
      additional suggestive linkages (3p24, 5q35, 11q22, and Xq12) were found in 606
      families with mean age at diagnosis of < or = 65 years. Although it is difficult
      to determine the true statistical significance of these findings, a conservative
      interpretation of these results would be that if major PC-susceptibility genes do
      exist, they are most likely located in the regions generating suggestive or
      significant linkage signals in this large study.

PMID- 15988681
TI  - Mediastinal staging 2005: pictures, scopes, and scalpels.
AB  - Staging of the mediastinum for lung cancer has matured dramatically with the
      advent of newer technologies in imaging and endoscopic surveillance. Some of
      these technologies such as positron emission tomography (PET) scanning are
      becoming mainstream in the evaluation of patients with clinically suspicious
      mediastinal disease as seen on computed tomography (CT), while others such as
      endobronchial ultrasound are reserved for specialty expertise and await
      validation. While much improvement has been made in the accurate preoperative
      staging of patients having surgery as the primary modality in lung cancer,
      controversy exists regarding the restaging of locally advanced cases after
      induction chemotherapy or chemoradiotherapy. A major concentration on these
      restaging issues is warranted since it is now generally agreed that sterilization
      of the mediastinum after induction therapy has an impact on the prognosis of
      patients with stage IIIA disease, and accurate staging after therapy may
      rationally guide diverse therapeutic interventions in these patients.

PMID- 15988682
TI  - Adjuvant chemotherapy in early-stage non-small cell lung cancer.
AB  - Approximately 80% of lung malignancies are non-small cell lung carcinoma (NSCLC).
      Patients diagnosed with early-stage disease (about 30% of patients) undergo
      surgery, but up to 50% develop local or distant recurrence. In an effort to
      improve survival for patients with resectable NSCLC, chemotherapy has been
      explored in the adjuvant setting. Several adjuvant trials were launched in the
      mid 1990s after an individual data-based meta-analysis suggested a 5% survival
      benefit at 5 years. Among those, the International Adjuvant Lung Cancer Trial
      (IALT) study, with 1,867 patients included, confirmed the benefit of
      postoperative chemotherapy in resected NSCLC. More recently, modern platinum
      containing doublets showed a 10% to 15% overall benefit compared to no adjuvant
      treatment. In this article, the current status of adjuvant chemotherapy is
      reviewed, and future prospects are discussed.

PMID- 15988683
TI  - Current standards and ongoing controversies in the management of locally advanced
      non-small cell lung cancer.
AB  - Despite the fact that nearly half of all patients with non-small cell lung cancer
      (NSCLC) present with stage III disease, this is the treatment setting with the
      least well-established standards. Generally treated with curative intent,
      patients with stage III disease usually receive more than one of the three main
      therapeutic approaches to lung cancer-surgery, radiation, and chemotherapy. In
      addition, the staging system encompasses a remarkably heterogeneous range of
      tumor burden and location within the rubric of stage III. Consequently, an
      individualized approach is often invoked to address particular concerns for
      resectability, toxicity, and patient and physician preferences. For patients with
      locally advanced NSCLC, therapeutic outcomes have improved overall for this
      population over the past few decades. While there exists a range of acceptable
      standard approaches to the treatment of stage III NSCLC, this review will
      describe several conclusions that have emerged and how they evolved.

PMID- 15988684
TI  - Prophylactic cranial irradiation with combined modality therapy for patients with
      locally advanced non-small cell lung cancer.
AB  - Central nervous system (CNS) metastasis is a significant problem for many
      patients with non-small cell lung cancer (NSCLC). The earlier data reported a
      high incidence of CNS metastasis in patients with locally advanced NSCLC who were
      treated with radiotherapy alone. However, poor control of both thoracic and
      extracranial systemic disease dominated the results of the early trials. The risk
      for CNS metastasis as the first site of failure remains a significant concern for
      patients who have completed modern combined modality therapy. With improvements
      in the treatment of thoracic and systemic disease, there is renewed interest in
      prophylactic cranial irradiation (PCI). The results from the Radiation Therapy
      Oncology Group (RTOG) trial of PCI to prevent CNS relapse in patients with
      locally advanced NSCLC are anticipated.

PMID- 15988685
TI  - Advances in cytotoxic chemotherapy for the treatment of metastatic or recurrent
      non-small cell lung cancer.
AB  - Improvements in drug development and clinical trial design have resulted in a
      wider range of treatment options for patients with advanced non-small cell lung
      cancer (NSCLC). Combination chemotherapy is the standard of care for medically
      fit patients. A variety of chemotherapeutic doublets, including nonplatinum
      combinations, with similar clinical activity are now available, allowing
      oncologists to match acceptable toxicity profiles to individual patients'
      comorbidities and preferences. Single-agent treatment of refractory or recurrent
      disease has been shown to improve survival and offer improved quality of life
      (QOL). For special patient populations, such as the elderly and patients with
      limited performance status (PS), treatment with single-agent chemotherapy results
      in modest survival benefits and combination chemotherapy may be appropriate for
      some of these patients.

PMID- 15988686
TI  - Current management of advanced non-small cell lung cancer: targeted therapy.
AB  - Lung cancer is one of the most frequent causes of cancer-related death in the
      United States. For patients with advanced non-small cell lung cancer (NSCLC),
      chemotherapy, alone or in combination with radiation therapy, is considered the
      standard treatment. Although this treatment may result in a modest improvement in
      patient survival, overall prognosis of these patients remains dismal, and the
      treatment is nonspecific, nonselective, and toxic. Therefore, new therapeutic
      strategies are needed. During the past decade, several molecules that contribute
      to lung cancer progression and metastasis have been identified. Growth factors
      and proangiogenic factors have been the focus of intense research in cancer since
      therapeutic approaches for their inhibition do exist. The role of these factors
      was studied in different organs and tumors and was found to be phenotypically
      distinct. Several molecular targeted therapies have shown efficacy and had been
      approved for treatment of specific cancers. Most advanced in clinical research
      for lung cancer are targeted therapies that inhibit the epidermal growth factor
      receptor (EGFR) and the vascular endothelial growth factor (VEGF) signaling
      pathways. Others are signaling pathway inhibitors. The first targeted therapy for
      lung cancer is gefitinib, an EGFR inhibitor, which was approved in several
      countries in 2003. Goals of molecular targeted therapy studies include the
      following: better understanding of the exact role of particular growth factors in
      specific tumors; establishment of new clinical study designs for biological
      agents; and tailoring appropriate combinations of conventional chemotherapy
      and/or radiotherapy with biological therapy for specific patients. Achievement of
      these goals will hopefully lead to incorporation of biological therapy into the
      current anticancer arsenal, for the benefit of lung cancer patients.

PMID- 15988687
TI  - Redefining bronchioloalveolar carcinoma.
AB  - Bronchioloalveolar carcinoma (BAC) is a subtype of non-small cell lung cancer
      (NSCLC) with distinct clinical and pathologic features. Although BAC appears to
      be on a pathologic continuum with adenocarcinoma, the most recent World Health
      Organization (WHO) classification system has set stringent criteria for the
      diagnosis. Though malignant, these cancers tend to be peripheral and grow in a
      lepedic fashion along the alveolar septae without parenchymal invasion. This
      clear distinction based on histopathology allows for a more definite separation
      of the natural history and behavior of BAC in clinical studies. Recent clinical
      trials of molecular targeted anticancer therapies have led to a deeper
      understanding of the unique features of this cancer and suggest that BAC may
      require a different therapeutic paradigm from other NSCLCs.

PMID- 15988688
TI  - New agents in the management of advanced mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a seemingly uncommon tumor whose
      incidence has in fact increased steadily and progressively over the last 30
      years. Indeed, an actual "epidemic" is expected in Europe over the next 20 years.
      Despite unquestionable improvement in the diagnostic methods at our disposal and
      the availability of new treatment strategies, the prognosis of MPM patients
      remains dramatically poor (12 to 18 months' median survival from diagnosis),
      although exceptional cases of long-survivors are reported in all literature
      series. The current review will cover the dramatic improvements in the treatment
      of this rare disease that have been recently achieved, as well as the promise
      that new, molecular-targeted therapies, such as bortezomid, mTOR ( m ammalian t
      arget o f r apamycin) inhibitors, and Met inhibitors, seem to offer for the next
      few years. With pemetrexed we now have a drug that is able to impact patient
      survival. Together with the newer drugs, rapidly emerging from the laboratory to
      be applied in the clinic, we have the hope of making further advances in the
      struggle against this disease.

PMID- 15988690
TI  - Response of protein synthesis to hypercapnia in rats: independent effects of
      acidosis and hypothermia.
AB  - Acute metabolic acidosis has been shown to inhibit muscle protein synthesis,
      although little is known on the effect of acidosis of respiratory origin. The aim
      of this study was to investigate the effect of acute respiratory acidosis on
      tissue protein synthesis. Rats (n = 8) were made acidotic by increasing the CO2
      content of inspired air to 12% for 1 hour. Similar rats breathing normal air
      served as controls (n = 8). Muscle and liver protein synthesis rates were then
      measured with L-[ 2H5 ]phenylalanine (150 micromol per 100 g body weight, 40
      mol%). The results show that protein synthesis is severely depressed in skeletal
      muscle (-44% in gastrocnemius, -39% in plantaris, and -24% in soleus muscles, P <
      .01) and liver (-20%, P < .001) in acidotic animals. However, because breathing
      CO2 -enriched air was found to lower body temperature by approximately 2 degrees
      C, in a second experiment (n = 10), the difference in body temperature between
      treated and control animals was minimized by gently wrapping rats breathing CO2 
      enriched air in porous cloths. This second experiment confirmed that respiratory
      acidosis depresses protein synthesis in muscle (-22% in gastrocnemius, P < .001; 
      19% in plantaris, P < .01; and -4% in soleus, P = NS). However, no effect on
      liver protein synthesis could be detected, suggesting that liver protein
      synthesis may be sensitive to changes in body temperature but is not affected by
      acute respiratory acidosis for 1 hour. The results show that respiratory acidosis
      inhibits protein synthesis in skeletal muscle and indicates that acidosis,
      whether of metabolic or respiratory origin, may contribute to loss of muscle
      protein in patients with compromised renal or respiratory function.

PMID- 15988691
TI  - Antisense oligonucleotides targeted against glucocorticoid receptor reduce
      hepatic glucose production and ameliorate hyperglycemia in diabetic mice.
AB  - Abstract Specific blockade of glucocorticoid receptor (GCCR) action in the liver
      without affecting the hypothalamus-pituitary-adrenal axis could be a novel
      pharmaceutical approach to treat type 2 diabetes. In the present study, we
      applied an antisense oligonucleotide (ASO) against GCCR (ASO-GCCR) to reduce the
      expression of liver GCCR and examined its impact on the diabetic syndrome in ob /
      ob and db / db mice. A 3-week treatment regimen of ASO-GCCR (25 mg/kg IP, twice
      per week) markedly reduced liver GCCR messenger RNA and protein expression with
      no alteration of GCCR messenger RNA expression in the hypothalamus, pituitary, or
      adrenal gland. The ASO-GCCR treatment lowered blood glucose levels by 45% and 23%
      in ob / ob and db / db mice, respectively, compared with those observed in the
      control group. The ASO-GCCR-treated mice also showed significant enhancement of
      insulin-mediated inhibition of hepatic glucose production during a euglycemic
      hyperinsulinemic clamp as well as marked reduction of phosphoenolpyruvate
      carboxykinase and glucose 6-phosphatase activity compared with control mice. The
      ASO-GCCR treatment did not change peripheral insulin sensitivity during the
      clamp. The ob / ob mice treated with ASO-GCCR had no significant difference in
      the plasma corticosterone and corticotropin levels compared with control mice.
      Lean mice receiving a similar treatment regimen of ASO-GCCR exhibited no change
      in blood glucose levels, oral glucose tolerance tests, or insulin tolerance
      tests. Our results demonstrate that selective inhibition of GCCR expression in
      the liver by the ASO-GCCR treatment reduced hepatic glucose production and
      improved blood glucose control under diabetic conditions.

PMID- 15988692
TI  - Changes in plasma antioxidant capacity and oxidized low-density lipoprotein
      levels in men after short-term cranberry juice consumption.
AB  - Low-density lipoprotein (LDL) oxidation is closely implicated in the development
      of atherosclerotic cardiovascular disease (CVD), and thus, reducing LDL
      susceptibility to oxidation with antoxidants could be of importance in CVD
      prevention. Flavonoids, polyphenolic compounds found in a large selection of
      fruits and vegetables, have been characterized as having a strong antioxidant
      potential, and intake of flavonoid-rich foods has been related to decreased
      morbidity and mortality from heart disease. The present study was therefore
      undertaken to investigate the effect of flavonoid-rich cranberry juice
      supplementation on plasma lipoprotein levels and LDL oxidation. For that purpose,
      21 men (age +/- SD, 38 +/- 8 years) were enrolled in a 14-day intervention and
      instructed to drink cranberry juice 7 mL/kg body weight per day. Physical and
      metabolic measures including plasma lipid and oxidized LDL (OxLDL) concentrations
      as well as antioxidant capacity were performed before and after the intervention.
      At baseline, we found that plasma OxLDL levels were significantly associated with
      waist circumference ( r = 0.47, P = .0296) as well as plasma triglyceride ( r =
      0.68, P = .0007) and apolipoprotein B ( r = 0.91, P < .0001) concentrations. The
      intervention led to a reduction in plasma OxLDL levels (-9.9% +/- 17.8%, P =
      .0131) and increase in antioxidant capacity (+6.5% +/- 10.3%, P = .0140).
      However, no relationship was found between both of these changes ( r = -.01, not
      significant). The intervention did not result in any improvement of plasma
      lipoprotein-lipid or inflammatory marker concentrations. Our results show that
      short-term cranberry juice supplementation is associated with significant
      increase in plasma antioxidant capacity and reduction in circulating OxLDL
      concentrations. Although the physiological relevance of our observations needs to
      be further examined, our study supports the potential role of antioxidant-rich
      foods in maintaining health and preventing CVD.

PMID- 15988693
TI  - Leptin responses to insulin administration in children with short stature.
AB  - Abstract The aim of the study was to investigate the effect of standard insulin
      tolerance test on plasma leptin levels in children with idiopathic short stature
      (ISS) and in children with growth hormone deficiency (GHD). Furthermore, plasma
      leptin levels were analyzed with regard to age, body mass index (BMI), and plasma
      levels of human growth hormone and of insulin-like growth factor-1 (IGF-1). Sixty
      three patients with a height below the third percentile, an age of 10.24 +/- 0.40
      years and a BMI standard deviation score (SDS) of -0.78 +/- 0.13 (weight SDS 
      0.07 +/- 0.12; height SDS -2.39 +/- 0.10) were investigated (mean +/- SD). Based
      on responses to insulin tolerance test, the patients were classified as ISS (n =
      49) or GHD (n = 14). Plasma leptin levels were significantly lower in all
      patients 60 minutes ( P < .001) and 120 minutes ( P < .001) after insulin
      administration. This effect was independent of GHD, and no difference in leptin
      decrease was found when comparing patients with ISS to those with GHD. A
      correlation was found when comparing plasma leptin levels of all patients to BMI
      SDS (r = 0.43; P < .001) and plasma IGF-1 levels (r = 0.31; P < .01).
      Furthermore, positive correlation was found when BMI SDS was compared to IGF-1 (r
      = 0.25; P < .05). In summary, we found that insulin administration in children
      with short stature decreases plasma leptin levels, equally in those with and
      without GHD.

PMID- 15988694
TI  - Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine
      levels of postmenopausal women with type 2 diabetes.
AB  - This study examined the independent and combined effects of diet and exercise on
      adipocytokine and inflammatory cytokines in postmenopausal women with type 2
      diabetes. Using a randomized, controlled design, 33 women (age, 50-70 years) were
      assigned to diet alone (D), exercise alone (EX), or diet + exercise (D + E) for
      14 weeks. Before and after the interventions, blood samples for adipocytokines
      and inflammatory markers were drawn, a meal test was performed, and abdominal fat
      distribution was measured by magnetic resonance imaging (MRI). Body weight
      decreased approximately 4.5 +/- 0.6 kg ( P < .05) after the D and D + E
      interventions, whereas only small changes in body weight were found with the
      exercise-alone intervention. Plasma C-reactive protein levels were decreased by
      approximately 15% with all 3 interventions, whereas leptin levels were reduced
      with the D and D + E intervention (D: pre = 48.7 +/- 6.0, post = 38.9 +/- 5.0
      ng/mL; D + E: pre = 38.5 +/- 6.0, post = 22.9 +/- 5.0 ng/mL; P < .05) with no
      differences between groups. There was a trend for leptin levels to decrease in
      the EX group ( P = .06). Plasma resistin levels were not altered by the 3
      interventions from pre- to posttreatment (D: pre = 6.9 +/- 0.6, post = 6.2 +/-
      0.4 ng/mL; D + E: pre = 5.6 +/- 0.6, post = 5.7 +/- 0.4 ng/mL; E: pre = 6.2 +/-
      0.6, post = 5.9 +/- 0.6 ng/mL, P > .05), and no differences in adiponectin and
      tumor necrosis factor alpha (TNF- alpha ) levels were found. Visceral adipose
      tissue and tumor necrosis factor alpha were the only predictors of calculated
      insulin resistance ( P < .05), explaining 43% of the variability. A typically
      prescribed weight loss program with lifestyle changes resulted in few changes in
      adipocytokines and inflammatory cytokines in older women with type 2 diabetes,
      suggesting that dramatic weight loss or clinical interventions are needed.

PMID- 15988695
TI  - Energy adaptation to glucocorticoid-induced hyperleptinemia in human beings.
AB  - Recombinant leptin therapy potently decreases food intake and body weight in
      aleptinemic individuals with leptin gene mutations. However, it is unknown
      whether manipulation of endogenous leptin secretion alters ingestive behavior in
      otherwise healthy subjects. We therefore assessed energy consumption during
      administration of hydrocortisone (HC), a known leptin secretagogue. Six healthy
      adults were admitted overnight on 2 occasions and given HC (12.5 mg/h IV) or
      saline infusion for 24 hours (8:00 am -8:00 am ) in a randomized crossover
      design. Total energy and macronutrient intake was calculated using a computerized
      nutrient analysis program. Blood sampling for measurement of leptin, cortisol,
      glucose, and insulin was performed at baseline and every 1 to 2 hours. A rise in
      plasma leptin level was noted after approximately 5 hours of HC infusion and was
      sustained throughout the study period. The total energy consumed was 3004 +/- 231
      kcal for saline and 2486 +/- 214 kcal for HC ( P = .005); breakfast energy values
      on day 1 were similar but energy values consumed at lunch, dinner, and day 2
      breakfast were all significantly lower during induced hyperleptinemia. Analysis
      of macronutrients indicated significant decreases in carbohydrate and fat intake
      during glucocorticoid-induced hyperleptinemia as compared with placebo. These
      results indicate that stimulation of native leptin secretion decreases energy
      consumption, similar to the effect observed with recombinant leptin therapy. To
      our knowledge, this is the first report documenting anti-ingestive responses to a
      leptin secretagogue. Because chronic glucocorticoid therapy is fraught with
      adverse effects, we suggest that nonsteroidal or steroidomimetic leptin
      secretagogues may be good candidates for anorectic and antiobesity drug
      development.

PMID- 15988696
TI  - Glucose and lipid metabolism after liver transplantation in inbred rats:
      consequences of hepatic denervation.
AB  - The liver plays a central role in glucose and lipid homeostasis. Because liver
      transplantation severs the hepatic nerves which influence this function, we
      hypothesized that insulin resistance and hyperlipidemia develop after liver
      transplantation, thus increasing the atherosclerotic risk. Therefore, we studied
      inbred rats 8 months after orthotopic liver transplantation (Tx, n = 39) or
      laparotomy (sham, n = 37) by either oral glucose tolerance test (Tx, n = 13;
      sham, n = 8), meal tolerance test (Tx, n = 9; sham, n = 13), or euglycemic
      hyperinsulinemic clamp with tritiated glucose infusion (Tx, n = 17; sham, n =
      16). We found that liver transplantation significantly increased basal hepatic
      glucose production (HGP) in the clamp study by 20% (37.3 +/- 2.2 vs 31.0 +/- 2.1
      micromol kg -1 .min -1 , P < .05) and fasting plasma low-density lipoprotein
      (LDL) cholesterol by 36% (0.79 +/- 0.06 vs 0.58 +/- 0.05 mmol/L, P < .05).
      However, it did not affect HGP, total glucose uptake, metabolic clearance rate of
      insulin, and suppression of plasma nonesterified fatty acids, which were all
      normal in response to rising plasma insulin concentrations in the dose-response
      clamp studies. The oral glucose tolerance test and meal tolerance test also
      showed normal glucose and nonesterified fatty acids homeostasis with adequate
      pancreatic insulin secretion and hepatic insulin clearance after liver
      transplantation. The only consequences of liver transplantation are increased
      basal HGP and plasma LDL cholesterol, which may be caused by persistent vagal
      denervation of the liver. Although insulin resistance is absent, elevated plasma
      LDL cholesterol increases the atherosclerotic risk.

PMID- 15988697
TI  - Serum glucose concentration and ACP1 genotype in healthy adult subjects.
AB  - Acid phosphatase locus 1 (ACP 1 ) or cytosolic low molecular weight protein
      tyrosine phosphatase is a polymorphic enzyme that can hydrolyze phosphotyrosine
      containing peptides of the human insulin receptor and of band 3 protein. High
      activity ACP 1 may favor an increase in serum glucose concentration through a
      depression of insulin action and through inactivation of aldolase,
      phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase induced by
      dephosphorylation of band 3 protein. In diabetic subjects, we have previously
      reported lower serum glucose concentration in subjects with low-activity ACP 1 A
      and AB phenotypes. We have now studied the relationship between serum glucose
      concentration and ACP 1 genotype in a sample of 137 healthy adult workers of our
      university. In males, serum glucose concentration is significantly higher in
      medium-high- than in low-activity ACP 1 genotypes. With advancing age in males,
      there is a progressive increase in glycemic differential between medium-high- and
      low-activity ACP 1 genotypes. The data suggest that normal variability of ACP 1
      genotype influences serum glucose concentration in normal individuals. Such
      influence depends on sex and in males becomes more marked with advancing age.

PMID- 15988698
TI  - Pharmacological inhibition of p38 MAP kinase results in improved glucose uptake
      in insulin-resistant 3T3-L1 adipocytes.
AB  - Inhibition of p38, a member of the mitogen-activated protein kinase family, has
      been shown to prevent the loss of GLUT4 protein expression in insulin-resistant
      adipocytes without improving insulin receptor substrate 1 (IRS-1) protein levels
      and presumably insulin signaling. Thus, it was unclear whether p38 inhibitors
      would have a beneficial effect upon insulin-stimulated glucose uptake. We
      evaluated the effects of p38 inhibition during the development of insulin
      resistance upon glucose uptake and components of the insulin signaling pathway to
      determine the therapeutic value of p38 inhibitors. Treatment with the specific
      p38 inhibitor, A304000, during the development of insulin resistance increased
      basal glucose uptake as well as glucose uptake in response to a subsequent
      insulin stimulation. p38 inhibition increased GLUT1 protein levels and prevented
      the loss of GLUT4. However, p38 inhibition did not prevent the loss of IRS-1
      protein levels or insulin signaling to PKB in insulin-resistant cells. Rapamycin,
      an inhibitor or mTOR, could partially improve insulin-stimulated glucose uptake
      through maintaining IRS-1 protein levels. Combined treatment with both A304000
      and rapamycin had an additive effect upon glucose uptake. These data indicate
      that p38 inhibition can enhance glucose uptake through regulating the expression
      of GLUT1 and 4, but did not prevent the development of insulin resistance.

PMID- 15988699
TI  - Normal triglyceride levels despite insulin resistance in African Americans: role
      of lipoprotein lipase.
AB  - Abstract Lipoprotein lipase (LPL), the enzyme responsible for hydrolyzing
      triglyceride (TG) in plasma lipoproteins, is a key regulator of plasma TG levels.
      In Caucasians, postheparin-LPL (PH-LPL) activity is impaired in the presence of
      insulin resistance and leads to elevated TG levels. However, African Americans
      are often both insulin-resistant and normotriglyceridemic. But in African
      Americans, the effect of insulin resistance on PH-LPL activity has not been
      studied. In African Americans, if insulin resistance is not associated with a
      decrease in PH-LPL activity, this could account for the simultaneous presence of
      insulin resistance and normotriglyceridemia. Therefore, our goal was to determine
      in African Americans the relationship between insulin resistance and PH-LPL
      activity. In a cross-sectional study of 107 nondiabetic African Americans (57 men
      and 50 women; age mean +/- SD, 35 +/- 8 years, range 22-50 years; body mass index
      31.6 +/- 7.9 kg/m 2 , range 18.5-54.7 kg/m 2 ), fasting TG levels and PH-LPL
      activity were determined. Visceral adipose tissue was measured by abdominal
      computed tomographic scan. Insulin resistance was determined by the insulin
      sensitivity index ( S I ). Subjects were divided into tertiles by S I . The range
      of S I in each tertile was 12.75 to 3.99, 3.87 to 2.20, 2.06 to 0.17 mU . L -1 .
      min -1 . Insulin resistance was defined as being in the third tertile. TG levels
      in the men and women were 82.2 +/- 35.5 versus 56.4 +/- 30.1 mg/dL, P < .001.
      There were no sex difference in PH-LPL activity (8.9 +/- 2.5 vs 9.6 +/- 3.2
      mmol/h per liter, P = .30) or S I (3.65 +/- 2.59 vs 3.23 +/- 1.89 L . mU -1 . min
      -1 , P = .49). Although 47% of the subjects were obese, only 4% of subjects had
      hypertriglyceridemia (TG > or =150 mg/dL). By 2 separate analyses, PH-LPL was a
      major determinant of TG levels. First, there was a significant inverse
      correlation between PH-LPL activity and TG levels (men: r = -0.46, P < .001;
      women: r = -0.28, P = .046). Second, in the multiple regression analysis with TG
      as the dependent variable and PH-LPL, age, sex, S I , and visceral adipose tissue
      as independent variables, adjusted R 2 was 54% and the effect of PH-LPL on TG
      levels was highly significant( P < .001). However, insulin resistance did not
      appear to influence PH-LPL activity. This is demonstrated in 3 ways: first, PH
      LPL activity was not different in the S I tertiles (9.10 +/- 2.75, 9.52 +/- 2.91,
      9.13 +/- 2.89 mmol/h per liter, P = .78); the correlation between PH-LPL and S I
      was not significant (men: r = 0.09, P = .51; women: r = -0.03, P = .78), and a
      multiple regression with PH-LPL as the dependent variable and age, S I , body
      mass index, and sex as independent variables, adjusted R 2 was <2% and the
      contribution of S I was not significant ( P = .53). Hence, in African Americans,
      increased PH-LPL activity is associated with a decrease in TG levels. The lack of
      an effect of insulin resistance on PH-LPL could allow LPL to clear TG even in the
      presence of insulin resistance and explain the coexistence of insulin resistance
      and normotriglyceridemia in African Americans.

PMID- 15988700
TI  - Inverse effects of the PPAR(gamma)2 Pro12Ala polymorphism on measures of
      adiposity over 15 years in African Americans and whites. The CARDIA study.
AB  - Few studies have addressed the association of the Pro12Ala polymorphism of the
      peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) gene with
      longitudinal measures of adiposity and insulin sensitivity during young
      adulthood, or reported on its relationship with these outcomes in African
      Americans. These issues were examined in the biracial Coronary Artery Risk
      Development in Young Adults (CARDIA) cohort, a population-based sample of 5115
      African Americans and whites followed prospectively over 15 years. Frequency of
      the Ala12 allele was 2.1% in African Americans and 12.8% in whites, consistent
      with previous reports. A generalized estimating equation method was used to
      simultaneously examine the cross-sectional and longitudinal relationships between
      the Pro12Ala polymorphism and the measures of adiposity and insulin sensitivity.
      The Pro12Ala polymorphism was significantly associated with mean 15-year levels
      of adiposity, but these associations were in opposite direction in the 2 racial
      groups. On average, African Americans carrying the Ala12 allele had a 1.1 kg/m2
      lower body mass index (BMI) ( P = .02) and whites a 0.6 kg/m2 higher BMI ( P =
      .01), as compared to Pro12 homozygotes. The Ala12 allele was also significantly
      associated with a decreased risk of incident insulin resistance syndrome in each
      race (OR = 0.44, P = .04 in African Americans; OR = 0.61, P = .01 in whites) and
      lower mean 15-year levels of fasting insulin ( P = .02), glucose ( P = .02), and
      homeostasis model assessment ( P = .01) in African Americans but not in whites.
      Important roles of BMI and ethnic background in influencing the complex
      relationships among PPAR gamma gene variation, adiposity, and insulin resistance
      are suggested.

PMID- 15988701
TI  - Younger, premenopausal women with major depressive disorder have more abdominal
      fat and increased serum levels of prothrombotic factors: implications for greater
      cardiovascular risk.
AB  - Major depressive disorder (MDD) is one of the most common psychiatric illnesses
      in the adult population. It is often associated with an increased risk of
      cardiovascular disease. We measured body fat distribution as well as plasminogen
      activator inhibitor-1 (PAI-1) concentration and factor VIII (fVIII) activity at
      8:00 am and 8:00 pm in 45 premenopausal women with MDD vs 28 healthy controls
      (age, 37 +/- 6.8 vs 35 +/- 6.5; weight [kg], 75.3 +/- 17.2 vs 67.9 +/- 10.2; mean
      +/- SD] participating in a prospective study of bone turnover, the POWER Study.
      At the time of evaluation, women with MDD were mildly depressed and mostly in
      clinical remission on antidepressants. After adjusting for body weight, women
      with MDD had greater waist circumference and abdominal fat as well as
      significantly higher evening (8:00 pm) PAI-1 and fVIII levels than controls. Even
      when age-, race-, and body mass index-matched subsets were compared, the MDD
      group continued to exhibit statistically higher PAI-1 and fVIII levels. The
      observed alterations in body fat distribution (increased abdominal fat) and
      prothrombotic factors (increased PAI-1 and fVIII) may be in part responsible for
      the increased risk of cardiovascular disease reported in association with major
      depression.

PMID- 15988702
TI  - Relationships between fasting plasma ghrelin levels and metabolic parameters in
      children and adolescents.
AB  - Recent findings suggest that ghrelin may have a beneficial effect on vasculature.
      In the present study, we examined the associations between plasma ghrelin
      concentration and metabolic parameters in children and adolescents. We measured
      fasting plasma ghrelin concentrations in 50 Korean children and adolescents (28
      boys and 22 girls, mean +/- SD age 12.6 +/- 2.7 years, body mass index 22.7 +/-
      5.1 kg/m 2 ), and analyzed the associations between fasting plasma ghrelin level
      and anthropometric measurements, metabolic parameters, leptin concentration, and
      fasting insulin level. We found that fasting plasma ghrelin concentration was
      negatively correlated with height, weight, body mass index, percent body fat,
      waist circumference, and hip circumference in both boys and girls. Fasting plasma
      ghrelin levels were significantly negatively correlated with triglycerides and
      fasting insulin levels and positively correlated with high-density lipoprotein
      cholesterol in boys, but not in girls. Our results thus demonstrate that higher
      plasma ghrelin levels have beneficial effects on metabolic parameters in boys and
      that the relationships between fasting plasma ghrelin levels and metabolic
      parameters differed according to sex.

PMID- 15988703
TI  - Biokinetics of buccal spray insulin in patients with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the metabolic effect of buccal spray insulin compared with
      subcutaneous regular insulin in patients with type 1 diabetes. RESEARCH DESIGN
      AND METHODS: This study compared plasma glucose, insulin, and C-peptide levels in
      18 patients with type 1 diabetes treated with subcutaneous regular or buccal
      spray insulin on 2 consecutive mornings. On day 1, patients were treated with
      their usual subcutaneous regular insulin regimens. On day 2, patients received
      buccal spray insulin. In the morning of both days 1 and 2, patients received a
      standard meal of 630 kJ. No intermediate or long-acting insulin was administered
      to patients on the morning of the test. Blood samples were collected for up to 4
      hours for biokinetic analysis. In a subset of 3 patients, premeal buccal spray
      insulin was administered for 2 entire consecutive days. In these patients,
      glucose levels were monitored using the glucose sensor monitoring system.
      RESULTS: Overall, there were no statistically significant differences in glucose,
      insulin, or C-peptide levels measured after administration of subcutaneous vs
      buccal spray insulin. However, at 90 and 120 minutes after subcutaneous regular
      insulin administration, significantly higher insulin levels and more prolonged
      hypoglycemic effect were detected compared with buccal spray insulin
      administration. In the 3 patients who received 1 day of regular and 2 entire days
      of buccal spray insulin, no significant differences were observed in glucose
      levels during the 3 days of glucose sensor monitoring. CONCLUSIONS: Insulin
      administered via the buccal spray formulation is as effective as the subcutaneous
      route in lowering blood glucose levels.

PMID- 15988704
TI  - Endurance running acutely raises plasma osteoprotegerin and lowers plasma
      receptor activator of nuclear factor kappa B ligand.
AB  - Abstract The balance of the 2 cytokines, osteoprotegerin (OPG) and the receptor
      activator of nuclear factor kappa B ligand (soluble (s)RANKL), is known to have
      considerable influence on bone formation and degradation. Plasma concentrations
      of OPG and (s)RANKL were determined in a total of 31 long-distance runners before
      and immediately after running distances of either 15 or 42.195 km, respectively.
      In both groups of endurance runners, a significant decrease of sRANKL was
      observed during the run, the extent of which correlated to the running distance.
      Furthermore, OPG increased only in runners covering the marathon distance of
      42.195 km. We hypothesize that the known positive effect of long-distance running
      on the skeletal mass may be mediated by the OPG/sRANKL system.

PMID- 15988705
TI  - Effects of raloxifene and low-dose simvastatin coadministration on plasma lipids
      in postmenopausal women with primary hypercholesterolemia.
AB  - Abstract Raloxifene and low-dose simvastatin can each reduce low-density
      lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL)
      cholesterol and triglycerides. The objective of this double-blind, 12-week study
      is to determine whether raloxifene and simvastatin coadministration gives added
      benefit beyond either monotherapy in affecting fasting lipoproteins and
      apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL
      cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d,
      simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10
      mg/d. Raloxifene, simvastatin, and coadministration therapy reduced mean LDL
      cholesterol by 10.5%, 23.3%, and 31.0% from baseline, respectively ( P < .003 vs
      baseline; P < .02 vs placebo), and mean apolipoprotein B by 10.4%, 24.2%, and
      30.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo).
      Each active treatment decreased non-HDL cholesterol compared with placebo ( P <
      .01). Coadministration treatment was more effective than either monotherapy in
      reducing LDL cholesterol ( P < .05). Coadministration treatment reduced mean
      apolipoprotein B ( P < .001) and non-HDL cholesterol ( P < .001) when compared
      with raloxifene, but was not significantly different when compared with
      simvastatin. Coadministration therapy increased HDL cholesterol and
      apolipoprotein A1 levels compared with placebo ( P < .02). No significant effect
      on triglycerides, very low density lipoprotein cholesterol, and lipoprotein (a)
      occurred with any active treatment. Raloxifene, simvastatin, and the
      coadministration therapy were generally well tolerated with clinical adverse
      effects similar to placebo. No woman had clinically significant elevated liver
      function tests requiring drug discontinuation. Further data on safety and lipid
      lowering effects are needed before raloxifene and statin coadministration may be
      considered as therapeutic interventions for treating postmenopausal women to
      achieve National Cholesterol Education Program-Adult Treatment Panel III
      treatment guidelines.

PMID- 15988706
TI  - Pravastatin does not affect insulin sensitivity and adipocytokines levels in
      healthy nondiabetic patients.
AB  - BACKGROUND: The effect of statins on insulin resistance is controversial and
      poorly studied in nondiabetic subjects. In addition, the effect of statins on
      leptin and adiponectin has never been studied. METHODS: Forty healthy nondiabetic
      volunteers (22 men and 18 women) aged 28 to 72 were randomized either to placebo
      or pravastatin 40 mg daily for a 12-week period. Insulin resistance, assessed
      using the Quantitative Insulin Sensitivity Check Index (QUICKI), as well as serum
      leptin and adiponectin levels, was measured at baseline and at the end of
      therapy. RESULTS: Pravastatin treatment decreased total cholesterol, low-density
      lipoprotein cholesterol, and triglycerides levels by 24%, 32%, and 14%,
      respectively ( P < .05 for all), but did not affect glucose and insulin levels,
      the (QUICKI) index, and adiponectin and leptin levels. When stratification was
      performed according to QUICKI index or sex, no significant differences were
      observed in the prevalues and postvalues of leptin, adiponectin, or QUICKI index
      in the pravastatin group. Adiponectin, leptin, and QUICKI index were
      statistically higher in women than in men ( P < .001 for both variables).
      Adiponectin was negatively correlated with body mass index (BMI; r = -0.39, P <
      .05) and positively correlated with the QUICKI index ( r = 0.54, P < .001) and
      with high-density lipoprotein cholesterol ( r = 0.50, P < .01). The relation
      between adiponectin and QUICKI index remained significant after adjustment for
      sex and BMI ( P = .005 and P = .007, respectively). Leptin was only related to
      BMI ( r = 0.57, P < .001) and to sex ( P < .001) with no significant correlations
      with lipid parameters or QUICKI index. Both sex and BMI are independent
      predictors of leptin ( P < .001 and P < .001). CONCLUSION: A 12-week treatment
      with pravastatin 40 mg/d does not change the QUICKI index and leptin and
      adiponectin levels in healthy volunteers. In addition, our results emphasize the
      importance of sex and BMI in the determination of both adiponectin and leptin.
      Adiponectin was also related to QUICKI index, whereas this relation was not found
      with leptin.

PMID- 15988707
TI  - Effect of elevated lipid concentrations on human skeletal muscle gene expression.
AB  - Dietary fatty acids regulate the abundance and activity of various proteins
      involved in the regulation of fat oxidation by functioning as regulators of gene
      transcription. To determine whether the transcription of key lipid metabolic
      proteins necessary for fat metabolism within human skeletal muscle are regulated
      by acute elevations in circulating free fatty acid (FFA) concentrations, 7
      healthy men underwent 3 randomized resting infusions of Intralipid (20%) with
      heparin sodium, saline and heparin sodium, or saline only for 5 hours. These
      infusions significantly elevated plasma FFA concentrations by 15-fold (to 1.67 +/
      0.13 mmol/L) in the Intralipid infusion trial, with modest elevations observed
      in the saline and heparin sodium and saline alone infusion groups (0.67 +/- 0.09
      and 0.49 +/- 0.087 mmol/L, P < .01 both vs Intralipid infusion). Analysis of
      messenger RNA (mRNA) concentration demonstrated that pyruvate dehydrogenase
      kinase isoform 4 (PDK4) mRNA, a key negative regulator of glucose oxidation, was
      increased in all trials with a 24-fold response after Intralipid infusion, 15
      fold after saline and heparin infusion, and 9-fold after saline alone. The PDK4
      increases were not significantly different between the 3 trials. The mRNA
      concentration of the major uncoupling protein within skeletal muscle, uncoupling
      protein 3, was not elevated in parallel to the increased plasma FFA as similar (
      approximately 2-fold) increases were evident in all trials. Additional genes
      involved in lipid transport (fatty acid translocase/CD36), oxidation (carnitine
      palmitoyltransferase I), and metabolism (1-acylglycerol-3-phosphate O 
      acyltransferase 1, hormone-sensitive lipase, and peroxisomal proliferator
      activated receptor-gamma coactivator-1alpha) were not altered by increased
      circulating FFA concentrations. The present data demonstrate that of the genes
      analyzed that encode proteins that are key regulators of lipid homeostasis within
      skeletal muscle, only the PDK4 gene is uniquely sensitive to increasing FFA
      concentrations after increased plasma FFA achieved by intravenous lipid infusion.

PMID- 15988709
TI  - Impaired response of cardiac autonomic nervous system to glucose load in severe
      obesity.
AB  - OBJECTIVE: This study was undertaken to further analyze the response of the
      cardiovascular autonomic nervous system (ANS) to changes in plasma insulin
      concentration induced by an oral glucose load. We hypothesized that, as a
      consequence of insulin resistance, an inability of insulin to increase the
      sympathetic modulation of heart rate (HR) and blood pressure (BP) would be
      observed in normotensive obese patients. METHODS: We used spectral analysis to
      measure simultaneously the short-term variability of HR and BP in 23 never-obese
      subjects and in 70 normotensive overweight or obese patients subdivided into 3
      subgroups: (1) overweight group (body mass index [BMI], 25-29.9 kg/m 2 ), n = 23;
      (2) class I-II obese group (BMI, 30-39.9 kg/m 2 ), n = 23; (3) class III obese
      group (BMI, > or =40 kg/m 2 ), n = 23. RESULTS: Oral glucose ingestion and the
      related increased insulinemia caused significant changes in the indices of
      sympathetic modulation (low-frequency [LF] power and LF/high-frequency ratio) of
      both HR and BP in normal weight, overweight, and obese subjects. However, the LF
      increments gradually decreased with the BMI classes, suggesting that sympathetic
      nervous system modulation in these subjects may be insulin-resistant. CONCLUSION:
      Obesity could develop resistance to the sympatho-excitatory effects of insulin
      that might play a role in the etiology of obesity. Spectral analysis of BP and HR
      can be used in research to evaluate the reactivity of the sympathetic nervous
      system in a manner that represents another feature of the obesity/insulin
      resistance syndrome.

PMID- 15988708
TI  - Modest weight loss improves insulin action in obese African Americans.
AB  - OBJECTIVE: We have previously shown that short-term energy restriction followed
      by modest lifestyle changes improves glucose tolerance for up to 1 year in obese
      individuals. The purpose of the present study was to determine the mechanism by
      which improvements in glucose tolerance occur in obese African Americans with
      insulin resistance and abnormal glucose tolerance. RESEARCH DESIGN AND METHODS:
      Nine subjects (53 +/- 2 years; body mass index, 37 +/- 3 kg/m 2 [mean +/- SEM])
      received a low-energy diet (3883 +/- 222 kJ/d) for 1 week, and then followed a
      modest lifestyle intervention program for up to 1 year. Body composition was
      estimated by hydrostatic weighing, and insulin secretion and action were assessed
      during a hyperglycemic clamp with superimposed arginine infusion and fat meal.
      Baseline and final tests were performed during weight stability. RESULTS:
      Significant improvements ( P < .05) were observed for body weight (-6.1 +/- 1.1
      kg), body composition (-5.5 +/- 1.3 kg fat mass), fasting plasma glucose (-1.1 +/
      0.3 mmol/L), fasting insulin (-52 +/- 21 pmol/L), oral glucose tolerance, and
      insulin action (+24%), defined as an increase in glucose disposal rate relative
      to plasma insulin concentration during the hyperglycemic clamp. These
      improvements were independent of an acute effect of energy restriction or weight
      loss, because body weight was stable. CONCLUSIONS: These results suggest that the
      improvements in glucose tolerance with a modest lifestyle intervention were
      attributable to an improvement in insulin action, and provide evidence that
      despite persistent obesity (body mass index, 34.7 +/- 2.4 kg/m 2 ), long-term
      benefits can be achieved with relatively small weight loss in obese African
      Americans.

PMID- 15988710
TI  - Genetic regulation of the variation of circulating insulin-like growth factors
      and leptin in human pedigrees.
AB  - Recent literature has shown that circulating levels of insulin-like growth factor
      I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk
      assessment of several chronic diseases including cancer, cardiovascular disease,
      diabetes mellitus and so on. The present study examined the extent of genetic and
      environmental influences on the populational variation of circulating IGF-I and
      IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The
      plasma levels of each of the studied biochemical indices were determined by
      enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative
      genetic analysis showed that the IGF-I variation was appreciably attributable to
      genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of
      the interindividual variation was explained by genetic determinants. Common
      familial environment factors contributed significantly only to IGF-BP-1 variation
      (23.3% +/- 7.8%). In addition, we examined the covariations between these
      molecules and between them and IGF-BP-3 and leptin that were previously studied
      in the same sample. The analysis revealed that the pleiotropic genetic effects
      were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for
      IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and
      0.15 +/- 0.05. The common environmental factors were consistently a significant
      source of correlation between all pairs (barring IGF-I and leptin) of the studied
      molecules; they were the sole predictors of correlation between IGF-I and IGF-BP
      1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of
      specific and common genetic pathways that in combination determine a substantial
      proportion of the circulating variation of these molecules.

PMID- 15988712
TI  - In-source decay of Boc-carbo-beta3-peptides in matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.

PMID- 15988713
TI  - Characterization of the improvised explosive urea nitrate using electrospray
      ionization and atmospheric pressure chemical ionization.
AB  - Mass spectra of urea nitrate were measured in electrospray ionization and in
      atmospheric pressure chemical ionization in the negative mode. In both ionization
      methods two characteristic adduct ions containing the intact molecule [urea
      nitrate+NO3]- and [urea nitrate+HNO3+NO3]- are shown. The structure of the two
      adduct ions was deduced using measurements of isotopically labeled urea nitrate.
      Collision-induced dissociation measurements of the adduct ions show typical
      losses enabling the identification of urea nitrate in trace amounts. Using these
      methods urea nitrate was identified in real cases.

PMID- 15988714
TI  - Development of a rapid method for the determination of glimepiride in human
      plasma using liquid-liquid extraction based on 96-well format micro-tubes and
      liquid chromatography/tandem mass spectrometry.
AB  - A semi-automated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method
      was developed for the determination of glimepiride in human plasma. The plasma
      samples were treated by liquid-liquid extraction (LLE) in 1.2 mL 96-well format
      micro-tubes. Glimepiride and the internal standard (IS) glibenclamide were
      extracted from human plasma by LLE, using a mixture of ethyl acetate/diethyl
      ether 50:50 (v/v) as the organic solvent. After vortexing, centrifugation and
      freezing, the supernatant organic solvent was evaporated. The analyte and IS were
      dissolved in a small volume of a reconstitution solution, an aliquot of which was
      analyzed by reversed-phase LC/MS/MS with positive ion electrospray ionization,
      using multiple reaction monitoring. The method proved to be sensitive and
      specific for both drugs, and statistical evaluation revealed excellent linearity
      for the range of concentrations 2.0-500.0 ng/mL with very good accuracy and inter
      and intra-day precisions. The proposed method enabled the rapid and reliable
      determination of glimepiride in pharmacokinetic or bioequivalence studies after
      per os administration of a 3 or 4 mg tablet of glimepiride.

PMID- 15988715
TI  - Structural characterization of 2-aminobenzamide-derivatized oligosaccharides
      using a matrix-assisted laser desorption/ionization two-stage time-of-flight
      tandem mass spectrometer.
AB  - Oligosaccharides were derivatized by reductive amination using 2-aminobenzamide
      (2-AB) and analyzed by matrix-assisted laser desorption/ionization two-stage time
      of-flight (MALDI-TOF/TOF) tandem mass spectrometry (MS/MS) in the positive ion
      mode. The major signals were obtained under these conditions from the [M+Na]+
      ions for all 2-AB-derivatized oligosaccharides. A systematic study was conducted
      on a series of 2-AB-derivatized oligosaccharides to allow rationalization of the
      fragmentation processes. The MALDI-TOF/TOF-MS/MS spectra of the [M+Na]+ ions of 2
      AB-derivatized oligosaccharides were dominated by glycosidic cleavages. These
      fragments originating both from the reducing and the non-reducing ends of the
      oligosaccharide yield information on sequence and branching. Moreover, the MALDI
      TOF/TOF-MS/MS spectra were also characterized by abundant cross-ring fragments
      which are very informative on the linkages of the monosaccharide residues
      constituting these oligosaccharides. MALDI-TOF/TOF-MS/MS analysis of 2-AB
      derivatized oligosaccharides, by providing structural information at the low
      picomole level, appears to be a powerful tool for carbohydrate structural
      analysis.

PMID- 15988716
TI  - Determination of the natural abundance delta15N of nicotine and related alkaloids
      by gas chromatography/isotope ratio mass spectrometry.
AB  - A method is described by which the natural abundance delta15N values of nicotine,
      analogues, and metabolites can be determined. The alkaloids are extracted from
      their biological matrix by solid-phase extraction and analysis is conducted using
      isotope ratio mass spectrometry interfaced to gas chromatography. Repeatability
      and precision are sufficient to allow differences in the delta15N values of less
      than 1.0 per thousand to be satisfactorily measured, with a standard deviation
      routinely less than 0.5 per thousand. The methodology has been tested by
      determining the changes in the delta15N values of nicotine, N-methyl-2
      phenylpyrrolidine and their respective demethylation products, nornicotine and 2
      phenylpyrrolidine, during biotransformation by cell suspension cultures of
      Nicotiana species. Sufficient precision and reproducibility were obtained to
      allow the kinetic isotope effects associated with the demethylation reaction to
      be calculated.

PMID- 15988717
TI  - Determination of proanthocyanidins in fresh grapes and grape products using
      liquid chromatography with mass spectrometric detection.
AB  - Fresh grapes and grape products, such as grape wine and grape juice, were
      analyzed for proanthocyanidins (PACs) using liquid chromatography with
      electrospray ionization mass spectrometric (MS) detection. PACs were successfully
      separated and analyzed on the basis of their protonated molecules, allowing the
      identification of PACs in different degrees of polymerization from monomers to
      oligomers (up to 7 units), and in various isomeric forms. Using reversed-phase
      high-performance liquid chromatography (HPLC) combined with MS detection, the PAC
      monomers, (+)-catechin (C), (-)-epicatechin (EC), (-)-catechin gallate (CG), and
      (-)-epicatechin gallate (ECG), were successfully quantified using selected ion
      monitoring (SIM) mode. Standard curves were fitted for each PAC ranging from 43.8
      to 5600 ng/mL for C, from 42.2 to 5400 ng/mL for EC, from 36.7 to 4700 ng/mL for
      CG, and from 39.8 to 5100 ng/mL for ECG. Good linearity (r2>0.999) was achieved
      for each analyte. The accuracy and precision (RSD) were within 10% (n=8) at the
      limit of detection. This method allows direct quantification of monomeric PACs in
      fresh grapes and grape-derived products. Additionally, flow injection analysis
      (FIA) was applied to estimate the concentration levels of PAC oligomers by
      comparing their FIA-MS peak areas, which were well correlated (r2=0.936) to the
      total concentrations of PAC monomers.

PMID- 15988718
TI  - Proteomics of gluten: mapping of the 1Bx7 glutenin subunit in Chinese Spring
      cultivar by matrix-assisted laser desorption/ionization.
AB  - The verification of the cDNA-deduced sequence of the high molecular weight
      glutenin subunit 1Bx7 in Chinese Spring cultivar was achieved by direct matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS) analysis of the tryptic fragments. The published sequence of the 1Bx7
      subunit contains 5 Lys and 15 Arg residues but, due to the presence of three Arg
      Pro bonds, which are generally resistant to cleavage by trypsin, or cleaved to a
      very limited extent by trypsin, 19 peptides can be predicted. The identification
      of the tryptic fragments was achieved by direct MALDI-MS analysis by using three
      different matrices (DHB, SA and HCCA) in combination with the most compatible
      sample preparation procedures in order to obtain the maximum sequence coverage.
      MALDI analysis of the 1Bx7 tryptic digest resulted in the identification of the
      expected peptides and additional fragments arising from non-specific cleavages;
      the fragments that were not detected are peptides with low mass (from 147.2 to
      317.4), so we obtained a sequence coverage of 98.8%. The results reported here
      also indicated that the sequence of the 1Bx7 subunit from cv. Chinese Spring is
      different from the cDNA-deduced sequence reported in the literature; in
      particular, a possible insertion of the hexapeptide QPGQGQ within the sequence
      Gln630-Tyr725 was suggested. Finally, it is possible to rule out glycosylation of
      the 1Bx7 subunit, or any other post-translational modification, to within the
      detection limits of the method.

PMID- 15988719
TI  - Prediction of insect adipokinetic hormone sequences assists in de novo structure
      elucidation.

PMID- 15988720
TI  - Use of carbon dioxide as collision gas in tandem mass spectrometry.

PMID- 15988721
TI  - An evaluation of the utility of in vacuo methylation for mass-spectrometry-based
      analyses of peptides.
AB  - In vacuo trimethylation of the N-terminus of a lyophilized peptide with methyl
      iodide was previously reported to enhance the peptide's signal in matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-MS) and to suppress alkali
      adduct formation in electrospray ionization mass spectrometry (ESI-MS). Both the
      signal enhancement and alkali adduct suppression observed for methylated peptides
      are believed to be due to the permanent positive charge on the N-terminus of the
      peptide resulting from the formation of a quaternary ammonium moiety. The present
      work evaluates the general utility of the in vacuo methylation procedure for the
      MS analysis of peptides, and specifically addresses the issue of whether the
      methylation of nucleophilic sites other than the N-terminal amine affects the
      MALDI signal of modified peptides. This work establishes that, although certain
      side-chain modifications are inevitable using present reaction conditions, the
      derivatization leads to significant MALDI-MS signal improvement. The experimental
      results demonstrate that the N-terminal trimethylammonium derivatives of peptides
      exhibit MALDI signals comparable to or exceeding those of arginine-containing
      standards such as angiotensin I. The advantages and limitations of the in vacuo
      methylation procedure are discussed.

PMID- 15988722
TI  - Development of a multiresidue method for analysis of major Fusarium mycotoxins in
      corn meal using liquid chromatography/tandem mass spectrometry.
AB  - A sensitive and reliable liquid chromatography/electrospray ionization tandem
      mass spectrometry (LC/ESI-MS/MS) method has been developed to determine, in a
      single run, eight trichothecenes, three fumonisins, zearalenone and alpha
      zearalenol, in corn meal samples. LC and MS conditions were varied to find the
      best compromise in terms of sensitivity and separation. An acceptable compromise
      was obtained using a C18 column thermostatted at 45 degrees C and a mobile phase
      gradient of methanol/water with 10 mmol/L formate buffer (pH 3.8). A multiple
      reaction monitoring program, in which fumonisins and trichothecenes (except
      nivalenol and deoxynivalenol) are acquired in positive ESI as [M+H]+ or [M+NH4]+,
      and all other compounds in negative ESI, was developed to match appropriate
      retention time windows. Sample preparation used a simple homogenization of the
      corn meal sample with acetonitrile/water (75:25, v/v) followed by extraction on a
      C18 cartridge and clean-up on a cartridge containing graphitized carbon black.
      Method detection limits were in the range 2-14 ng/g, with the exception of
      nivalenol (27 ng/g), deoxynivalenol (40 ng/g) and 15-acetyldeoxynivalenol (30
      ng/g). Good accuracy (recoveries 81-104%) and precision (RSD 4-11%) were obtained
      by performing calibration using a spiked analyte-free extract.

PMID- 15988723
TI  - Development of a low volume plasma sample precipitation procedure for liquid
      chromatography/tandem mass spectrometry assays used for drug discovery
      applications.
AB  - The demand for high sensitivity bioanalytical methods has dramatically increased
      in the drug discovery stage; in addition, there has been a growing trend of
      reducing the sample volume that is required for these assays. A sensitive high
      performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedure
      has been developed and tested to meet these needs. The assay requires only a low
      plasma sample volume (10 microL) and employs a protein precipitation procedure
      using a 1:6 plasma/acetonitrile ratio. The supernatant is injected directly into
      the LC/MS/MS system using the selected reaction monitoring (SRM) procedure for
      detection. A generic HPLC gradient based on a methanol/water mobile phase with a
      flow rate set to 0.8 mL/min was used. The test method showed very good linearity
      between 0.1-1000 ng/mL (R2 = 0.9737), precision (%RSD = 6-9), accuracy (%RE = -2)
      and reproducibility (%RSD = 11). A drug discovery IV/PO study was assayed using
      both the new low volume method and our standard volume (50 microL) method. The
      correlation of the two sets of data from the two methods was excellent (R2 =
      0.9287). This new assay procedure has been successfully used in our laboratory
      for over 100 different rat or mouse discovery PK studies.

PMID- 15988724
TI  - Rapid comparison of diacetylmorphine on banknotes by tandem mass spectrometry.
AB  - A procedure is described for the determination of the distribution of the
      contamination of banknotes with controlled drugs using tandem mass spectrometry.
      The method is illustrated using diacetylmorphine, which is the major active
      component of heroin. A series of banknotes is introduced into the mass
      spectrometer and the intensities of two product ions (m/z 328 and 268) derived
      from the precursor protonated molecule (m/z 370) are recorded. A banknote is
      considered contaminated if it shows a significant peak for both product ions, and
      if the ratio of intensities of these two peaks falls within accepted limits. The
      distribution of diacetylmorphine on sterling banknotes taken from general
      circulation within the UK can be modelled by an arcsin (square root)
      transformation of the data or by a log transformation of the data with a higher
      proportion of contamination. The two models were found to be in close agreement,
      predicting an upper limit (at 99.9% confidence) of contamination on banknotes
      from general circulation between 9 and 10%. The percentage contamination in a
      case study was calculated and compared to the background distribution using the
      two models proposed. This comparison revealed that the contamination present in
      the case study was inconsistent with that present on banknotes in general
      circulation.

PMID- 15988725
TI  - Comparison of negative and positive ion electrospray ionization mass spectra of
      calmodulin and its complex with trifluoperazine.
AB  - The protein calmodulin (apoCaM) undergoes a conformational change when it binds
      calcium. This structure of the protein (Ca4CaM) is a dumbbell-shaped molecule
      that undergoes a further profound conformational change on binding of the
      antipsychotic drug trifluoperazine (TFP). Experimental conditions were developed
      to prepare samples of apoCaM, Ca4CaM and Ca4CaM/TFP that were substantially free
      of sodium. The effects of the conformational changes of calmodulin on the charge
      state distributions observed in positive ion and negative ion electrospray
      ionization (ESI) mass spectra were examined. Conversion of apoCaM into Ca4CaM was
      concomitant with a change in the negative ion ESI mass spectrum whereby the 16-
      ion was the most abundant ion observed for the apo form and the 8- ion was the
      most abundant for the complex. In contrast, in the positive ion ESI mass spectra
      of apoCaM and Ca4CaM, the most abundant species in each case was the 8+ ion. When
      a complex of Ca4CaMwith TFP was prepared, the most abundant species was the 5+
      ion. This is consistent with a conformational change of Ca4CaM that rendered some
      basic sites inaccessible to ionization in the ESI process. Using the same
      Ca4CaM/TFP mixture, no complex with TFP was observed in negative ion ESI mass
      spectra. These observations are discussed in the context of the structural
      changes that are known to occur in calmodulin, and suggestions are made to
      explain the apparently conflicting data. The results reported here reflect on the
      validity of using differences in charge-state distributions observed in ESI mass
      spectra to assess conformational changes in proteins.

PMID- 15988726
TI  - On-line desalting and determination of morphine, morphine-3-glucuronide and
      morphine-6-glucuronide in microdialysis and plasma samples using column switching
      and liquid chromatography/tandem mass spectrometry.
AB  - A sensitive and reproducible method for the determination of morphine and the
      metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was
      developed. The method was validated for perfusion fluid used in microdialysis as
      well as for sheep and human plasma. A C18 guard column was used to desalt the
      samples before analytical separation on a ZIC HILIC (hydrophilic interaction
      chromatography) column and detection with tandem mass spectrometry (MS/MS). The
      mobile phases were 0.05% trifluoroacetic acid (TFA) for desalting and
      acetonitrile/5 mM ammonium acetate (70:30) for separation. Microdialysis samples
      (5 microL) were directly injected onto the system. The lower limits of
      quantification (LLOQ) for morphine, M3G and M6G were 0.50, 0.22 and 0.55 ng/mL,
      respectively, and the method was linear from LLOQ to 200 ng/mL. For plasma, a
      volume of 100 microL was precipitated with acetonitrile containing internal
      standards (deuterated morphine and metabolites). The supernatant was evaporated
      and reconstituted in 0.05% TFA before the desalting process. The LLOQs for sheep
      plasma were 2.0 and 3.1 ng/mL and the ranges were 2.0-2000 and 3.1-3100 ng/mL for
      morphine and M3G, respectively. For human plasma, the LLOQs were 0.78, 1.49 and
      0.53 ng/mL and the ranges were 0.78-500, 1.49-1000 and 0.53-500 ng/mL for
      morphine, M3G and M6G, respectively.

PMID- 15988727
TI  - High-throughput biological sample analysis using on-line turbulent flow
      extraction combined with monolithic column liquid chromatography/tandem mass
      spectrometry.
AB  - A high-throughput liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      method, which combines on-line sample extraction through turbulent flow
      chromatography with a monolithic column separation, has been developed for direct
      injection analysis of drugs and metabolites in human plasma samples. By coupling
      a monolithic column into the system as the analytical column, the method enables
      running 'dual-column' extraction and chromatography at higher flow rates, thus
      significantly reducing the time required for the transfer and mixing of extracted
      fraction onto the separation column as well as the time for gradient separation.
      A strategy of assessing and reducing the matrix suppression effect on the on-line
      extraction LC/MS/MS has also been discussed. Experiments for evaluating the
      resolution, peak shape, sensitivity, speed, and matrix effect were conducted with
      dextromethorphan and its metabolite dextrorphan as model compounds in human
      plasma matrix. It was demonstrated that the total run time for this assay with a
      baseline separation of two analytes is less than 1.5 min.

PMID- 15988728
TI  - Characterization of moenomycin antibiotics from medicated chicken feed by ion
      trap mass spectrometry with electrospray ionization.
AB  - The antimicrobial moenomycin, commonly used as a growth promoter in livestock,
      was isolated from medicated chicken feed. The purified extract was subjected to
      reversed-phase liquid chromatographic separation followed by structural
      characterization using ion-trap mass spectrometry (ITMS), which allowed
      identification of five moenomycins (A, A12, C1, C3, and C4) as the major
      components. The fragmentation patterns of the protonated and deprotonated
      moenomycin molecules, as well as of a series of sodium adducts, were investigated
      using ITMS after electrospray ionization. While the protonated molecules [M+H]+
      proved highly unstable and underwent extensive in-source fragmentation, isolation
      and activation of the [M--H]- ions (m/z 1580 for moenomycin-A) yielded simple
      mass spectra with a dominant base peak corresponding to the loss of the carboxy
      glycol and the C25-hydrocarbon chain (m/z 1152 for moenomycin-A). Further study
      of this fragment ion in an MS3 experiment gave rise to a peculiar product ion
      (m/z 902 for moenomycin-A) that was attributed to the expulsion of a carbohydrate
      moiety representing a central building block of the linear molecule. In positive
      ion mode the generation of the mono-sodiated adduct ions, [M+Na]+, was promoted
      by amending the mobile phase with 100 microM sodium acetate, but this also
      resulted in higher adducts of the type [M+2Na--H]+ and [M+3Na--2H]+ arising from
      the formation of the sodium salts of the phosphate acid diester and subsequently
      of the carboxylic acid. Substantial differences among the fragment-rich product
      ion profiles of the three species were observed, and could in part be traced back
      to the mode of complexation of the additional sodium cation(s).

PMID- 15988729
TI  - Structural characterization of flavonol di-O-glycosides from Farsetia aegyptia by
      electrospray ionization and collision-induced dissociation mass spectrometry.
AB  - This study reports the application of mass spectrometric methods to characterize
      unknown flavonoids of the herb Farsetia aegyptia Turra (Crucifereae). High
      performance liquid chromatography was performed in combination with UV-photodiode
      array detection (LC/UV-DAD) and electrospray ionization mass spectrometry (LC/ESI
      MS) in both positive and negative ion modes. Collision-induced dissociation (CID)
      mass spectral data were obtained off-line by nanospray (nano-ESI) analysis, which
      provided a wealth of information and led to the structural proposal of the
      flavonol di-O-glycosides present in the herb extract. In addition to the mass
      spectral data, we also report NMR data for the major compound which allowed the
      completion of its structural elucidation. The Farsetia aegyptia Turra herb
      extract was found to contain three flavonol di-O-glycosides containing a
      monosaccharidic residue linked to the 3-O position and a disaccharidic residue
      linked to the 7-O position; the major compound was characterized as the new
      flavonoid, isorhamnetin 3-O-alpha-L-arabinoside 7-O-[beta-D-glucosyl-1 --> 2]
      alpha(L)rhamnoside. Different types of CID spectra, i.e., low-energy [M+H]+,
      [M+Na]+ and [M--H]- spectra as well as high-energy [M+Na]+ spectra, were
      evaluated with respect to their utility to locate the O-linked saccharidic
      residues in flavonol di-O-glycosides and to determine the sequence in the
      disaccharidic part. In agreement with previously published data, the 3-O-glycosyl
      residue was more readily lost from the protonated molecule than the 7-O-glycosyl
      residue. The opposite behavior was noted for the fragmentation of the
      deprotonated and sodiated molecules. Radical ions were observed in the high
      energy [M+Na]+ CID spectra which provided supporting information on the
      glycosylation positions.

PMID- 15988730
TI  - Determination of the geographical origin of green coffee by principal component
      analysis of carbon, nitrogen and boron stable isotope ratios.
AB  - In this study we show that the continental origin of coffee can be inferred on
      the basis of coupling the isotope ratios of several elements determined in green
      beans. The combination of the isotopic fingerprints of carbon, nitrogen and
      boron, used as integrated proxies for environmental conditions and agricultural
      practices, allows discrimination among the three continental areas producing
      coffee (Africa, Asia and America). In these continents there are countries
      producing 'specialty coffees', highly rated on the market that are sometimes
      mislabeled further on along the export-sale chain or mixed with cheaper coffees
      produced in other regions. By means of principal component analysis we were
      successful in identifying the continental origin of 88% of the samples analyzed.
      An intra-continent discrimination has not been possible at this stage of the
      study, but is planned in future work. Nonetheless, the approach using stable
      isotope ratios seems quite promising, and future development of this research is
      also discussed.

PMID- 15988731
TI  - Acetonitrile-induced unfolding of the photosystem II manganese-stabilizing
      protein studied by electrospray mass spectrometry.
AB  - In this paper an acetonitrile-induced unfolding of the manganese-stabilizing
      protein (MSP) of photosystem II was discovered. More distinct unfolding states of
      MSP were identified than previously by using mainly electrospray ionization mass
      spectrometry (ESI-MS), together with fluorescence spectra and far-UV circular
      dichroism (CD) at pH 2.0, 6.2 or 11.6, and with acetonitrile concentrations from
      0 to 50%. At pH 6.2 with acetonitrile concentration changing from 0 to 10%,
      relatively broad charge-state distributions and poor intensity were observed in
      ESI-MS, indicating the presence of coexisting conformers. It was concluded that
      the structure of the MSP protein is unlikely to be a tightly folded form. When
      the concentration of acetonitrile was 20-40%, simulating the state in the
      biological membrane, changes in the state of unfolding of MSP were observed to a
      certain extent using ESI-MS, fluorescence and CD spectroscopy. The charge-state
      distribution in ESI-MS was found to move toward high states (from 13+ to 27+ to
      15+ to 31+) with increasing acetonitrile concentration. At pH 2.0, the MSP
      structure is rearranged into an unfolded state, and at pH 11.6 the MSP structure
      is induced to assume another unordered state by deprotonation of appropriate
      residues. An interesting observation was that a second peak envelope emerged with
      20-50% acetonitrile in the medium at pH 11.6.

PMID- 15988732
TI  - Enhancement of phosphoprotein analysis using a fluorescent affinity tag and mass
      spectrometry.
AB  - A fluorescent affinity tag (FAT) was synthesized and was utilized to selectively
      modify phosphorylated serine and threonine residues via beta-elimination and
      Michael addition chemistries in a 'one-step' reaction. This labeling technique
      was used for covalent modification of both phosphoproteins and phosphopeptides,
      allowing identification of these molecular species by fluorescence imaging after
      solution- or gel-based separation methods. In addition to the strong fluorescence
      of the rhodamine tag, a commercially available antibody can be used to enrich low
      abundance post-labeled phosphopeptides present in complex mixtures. Application
      of this methodology to phosphorylation-site mapping has been evaluated for a
      phosphoprotein standard, bovine beta-casein. Initial results demonstrated low
      femtomole detection limits after fluorescence image analysis of FAT-labeled
      proteins or peptides.

PMID- 15988733
TI  - Dissociation of peptide ions by fast atom bombardment in a quadrupole ion trap.
AB  - A new technique for fragmentation of cations and anions of peptides stored in ion
      traps including radiofrequency devices is described. The technique involves
      irradiation of peptide ions by a beam of particles generated by a fast atom
      bombardment (FAB) gun. This irradiation leads to fragmentation of N--C(alpha)
      backbone bonds (c- and z-fragments) and S--S bonds for cations and C(alpha)-C
      backbone bonds (a- and x-fragments) for anions of peptides. The fragmentation
      patterns observed are hypothesized to be due to the interaction of peptide ions
      with metastable, electronically excited species generated by the FAB gun.
      Interaction of a metastable atom A* with a peptide n-cation M(n+) leads to the
      electron transfer from the metastable atom to the polycation through the
      formation of an ion-pair collision complex A(+.) . . . M((n-1)+.) and subsequent
      fragmentation of the peptide cation. Thus, for polycations, this metastable
      induced dissociation of ions (MIDI) is similar to the phenomenon of electron
      capture dissociation (ECD). Interaction of A* with an anion leads to the
      deexcitation of the metastable species and detachment of an electron from the
      anion. This in turn leads to backbone fragmentation similar to that in electron
      detachment dissociation (EDD). The MIDI technique is robust and efficient, and it
      is applicable to peptides in as low charge states as 2+ or 2-.

PMID- 15988734
TI  - Life-threatening third-trimester hemorrhage following a vanishing twin phenomenon
      in early pregnancy.

PMID- 15988735
TI  - Is there an increased rate of megacystis in twins?

PMID- 15988736
TI  - Congenital pulmonary lymphangiectasia presenting as nonimmune fetal hydrops and
      severe respiratory distress at birth: not uniformly fatal.
AB  - Pulmonary lymphangiectasia is a rare cause of respiratory distress in the newborn
      associated with a very poor outcome. We describe three premature newborns
      presenting at birth with nonimmune hydrops, bilateral chylothorax, and severe
      respiratory distress in the immediate newborn period secondary to pulmonary
      lymphangiectasia. We review the similarities of these cases and discuss their
      antenatal and neonatal course. One patient survived and is thriving at 9 months
      of age. With continuing advances in antenatal and neonatal care, an improved
      outcome may be possible in what was previously described as a uniformly fatal
      condition.

PMID- 15988738
TI  - Burden of rhinitis in children with asthma.
AB  - Although the clinical association of allergic rhinitis and asthma has been
      recognized for centuries, in recent years the association appears to be stronger
      than was reported previously. However, data for children are less clear, and some
      studies indicate that results observed in developing countries may differ from
      those observed in Western populations. We therefore intended to document the
      association of rhinitis with pediatric asthma in terms of caregivers' perception,
      physician practice, and file records. Asthmatic children aged 3-16 years with at
      least 1-year follow-up in an allergy-asthma outpatient clinic were invited to
      participate in the study during a 10-month interval. In addition to a face-to
      face questionnaire-based interview, file records were evaluated retrospectively
      to obtain information relating to asthma and rhinitis. Of 396 patients included
      in the study, 369 with consistent replies were included in the analyses. The mean
      age of the study group was 10.6 +/- 0.2 (mean +/- SEM) years, and a greater
      proportion of the respondents were male (63.7%), atopic (78.3%), and mildly
      asthmatic (50.7%). House dust mite and grass pollens were the most commonly
      sensitized allergens (50.7% and 46.9%, respectively). Although only 5.4% of our
      study population regarded themselves as rhinitic and 23.8% had been diagnosed
      with allergic rhinitis according to the file records, almost 57.7% of patients
      had required medications for rhinitis within the last year, and 68.8% had
      findings consistent with allergic rhinitis. Furthermore, 41.2% and 58.8% reported
      that their rhinitis symptoms caused a significant burden in their daily life and
      exacerbated their asthma, respectively, and almost 50% felt that their rhinitis
      had not been given significant consideration by their physician. In conclusion,
      although we report a large discrepancy between caregivers' perception of
      rhinitis, documentation in file records, and treatments for rhinitis, the
      allergic rhinitis prevalence determined in the survey and the medication use for
      rhinitis appeared to be in agreement. We recommend a greater effort be made to
      identify, label, and educate children with rhinitis and their families in asthma
      outpatient clinics.

PMID- 15988737
TI  - In vitro studies of calcium phosphate glass ceramics with different solubility
      with the use of human bone marrow cells.
AB  - Two glass ceramics in the CaO--P2O5--MgO system with the incorporation of K2O or
      TiO2 oxides were prepared with the goal of using them as potential bone graft
      substitutes. The incorporation of TiO2 and K2O led to the preparation of specific
      crystalline phases in the structure of the glass ceramics, which show different
      degrees of biodegradation. In fact, the 45CaO--45P2O5--5MgO--5K2O has been
      previously demonstrated to be much more soluble in aqueous solutions than the
      45CaO--37P2O5--5MgO--13TiO2 glass ceramic. The in vitro biological activity of
      the two calcium phosphate glass ceramics was studied with the use of human bone
      marrow osteoblast cell cultures maintained for 28 days, and seeded materials were
      assessed for cell proliferation and function. The Ti-containing glass ceramic
      showed a stable surface throughout the culture time, on macroscopic and SEM
      observation. Osteoblast cells proliferated gradually, especially during the third
      week, with a high alkaline phosphatase activity and formation of a mineralized
      matrix. On SEM observation, attached cells appeared with a spread-polygonal
      morphology typical of the osteoblast cells, with extensive cell-to-cell contact.
      Cell behavior on the seeded material was similar to that found on cultures
      performed on tissue-culture-grade polystyrene; except for the presence of lower
      cell numbers during the first 2 weeks. By contrast, the K-containing glass
      ceramic showed a highly instable surface with dissolution/precipitation processes
      occurring throughout the culture time. Few cells adhered to the material surface,
      and subsequent proliferation was also hindered, especially from the first week
      onwards. Cell numbers were significantly lower than those observed in the Ti
      containing glass ceramic during most of the incubation time. Results suggest that
      the different in vitro biological behavior of these two glass ceramics is mainly
      due to the significant differences in the surface degradation rate, which is
      directly correlated to the chemical composition of the mother glass.

PMID- 15988739
TI  - Tubulin glycylation and glutamylation deficiencies in unconventional insect
      axonemes.
AB  - Though the 9+2 axonemal organization has generally been conserved throughout
      metazoan evolution, insect spermatozoa possess a substantial variety in axoneme
      ultrastructure, displaying different axonemal patterns. Therefore, insects
      provide a wide range of models that may be useful for the study of the mechanisms
      of axoneme assembly. We have used antibodies specific for glutamylated,
      monoglycylated, and polyglycylated tubulin to investigate the tubulin isoform
      content expressed in the unorthodox sperm axonemes of four insect species
      belonging to both of the superorders Palaeoptera and Neoptera. Each one of these
      axonemal models exhibits distinctive structural features, either showing the
      typical radial organization endowed with a ninefold symmetry or consisting of an
      helical arrangement with up to 200 microtubular doublets, but in all cases these
      axonemes share the absence of a microtubule central pair. Our results showed that
      all these atypical patterns are characterized by a dramatic decrease in both
      tubulin glycylation and glutamylation levels or even lack of both
      polymodifications. These data provide the first examples of a simultaneous
      extreme reduction or even absence of both polymodifications in axonemal tubulin.
      Given the unrelated positions of the analyzed species in the insect phylogenetic
      tree, this common feature is probably not due to evolutionary relationships.
      Therefore, our findings support the hypothesis of the existence of a correlation
      between the low level of polymodifications and the lack of a microtubule central
      pair in these peculiar insect flagellar axonemes, similarly as was previously
      proposed for cilia of Tetrahymena glycylation site mutants.

PMID- 15988740
TI  - Myosin genes in Tetrahymena.
AB  - This report presents an initial comparison of motor, neck, and tail domains of
      myosin genes in Tetrahymena thermophila. An unrooted phylogenetic tree drawn from
      alignment of predicted amino acid translations determined the relationship among
      13 myosins in Tetrahymena and their relationship to the myosin superfamily. The
      myosins in Tetrahymena did not align with any of the previously named myosin
      classes. Twelve of the Tetrahymena myosins form a new class designated as XX. The
      other Tetrahymena myosin is divergent from the twelve. Surprisingly, none of the
      myosins in Tetrahymena aligned with either class I, class II, or class V myosins.
      Apparent absence of a class II myosin is an indication that cytokinesis in
      Tetrahymena either utilizes an unconventional myosin or does not require a myosin
      motor.

PMID- 15988741
TI  - Impact of sirolimus-eluting stents on outcomes of patients treated for acute
      myocardial infarction by primary angioplasty.
AB  - Sirolimus-eluting stents (SESs) are currently being used in patients undergoing
      percutaneous coronary intervention (PCI). SESs have not been evaluated in the
      treatment of acute myocardial infarction by primary angioplasty. We report our
      initial experience with SESs implanted during primary angioplasty. One hundred
      and three patients were treated within 12 hr after onset of acute myocardial
      infarction (AMI) with primary angioplasty and SES implantation. Those patients
      were compared to 504 patients treated with bare metal stents (BMSs). Angiographic
      success (TIMI flow grade 3 and residual stenosis < 50%) was completed in 98% of
      patients with SESs and no subacute stent thrombosis was reported. In-hospital
      outcomes were similar in the SES and BMS groups. At 6 months, major cardiac
      events were less frequent in the SES group than in the BMS group (9% vs. 24%,
      respectively; P < 0.001), driven by a lesser need for repeat revascularization
      with SESs (1% vs. 10.3% with BMSs; P = 0.014). Mortality at 6 months was 7% with
      SESs and 11% with BMSs (P = 0.14). SESs are safe and effective for the treatment
      of AMI by primary angioplasty. As compared to BMSs, SESs improve long-term
      outcome after AMI, mainly by reducing the need for repeat revascularization.

PMID- 15988742
TI  - Poor long-term patient and graft survival after primary percutaneous coronary
      intervention for acute myocardial infarction due to saphenous vein graft
      occlusion.
AB  - Primary percutaneous coronary intervention (PCI) for ST segment elevation
      myocardial infarction (STEMI) due to saphenous vein graft (SVG) occlusion has
      been associated with poor procedural results and poor short-term outcomes, but
      long-term graft patency and patient survival have not been evaluated. Consecutive
      patients (n = 2,240) with STEMI treated with primary PCI from 1984 to 2003 were
      followed for 6.6 years (median). Follow-up angiography was obtained in 80% of
      hospital survivors following primary PCI for SVG occlusion at 2.3 years (median).
      Patients with primary PCI for SVG occlusion (n = 57) vs. native artery occlusion
      had more prior MI, advanced Killip class, and three-vessel coronary disease and
      lower acute ejection fraction (EF). Patients with SVG occlusion had lower rates
      of TIMI 3 flow post-PCI (80.7% vs. 93.6%; P = 0.0001), higher in-hospital
      mortality (21.1% vs. 8.0%; P = 0.0004), and lower follow-up EF (49.3% vs. 54.7%;
      P = 0.055). Culprit SVGs were patent in 64% of patients at 1 year and 56% at 5
      years. Late survival was strikingly worse in patients with primary PCI for SVG
      occlusion vs. native vessel occlusion (49% vs. 76% at 10 years), and SVG
      occlusion was the second strongest predictor of late cardiac mortality by
      multivariate analysis (HR = 2.11; 95% CI = 1.38-3.23; P = 0.0006). Patients with
      STEMI due to SVG occlusion treated with primary PCI have poor acute procedural
      results, frequent late reocclusion, and very high late mortality. The
      introduction of new adjunctive therapies (distal protection, thrombectomy, and
      drug-eluting stents) may improve short-term outcomes, but improved long-term
      outcomes may require new and more durable revascularization strategies.

PMID- 15988743
TI  - Circular dichroism studies on repeating polypeptide sequences of abductin.
AB  - The secondary structure of abductin was investigated by CD and NMR studies of
      several synthetic peptides. Results obtained with these peptides showed the
      dominant conformations to be the polyproline II (PPII) structure in aqueous
      solution and different types of beta-turns in the less polar solvent
      trifluoroethanol. Accordingly, a preliminary structure-elasticity relationship
      for abductin, not unlike that currently accepted for elastin, is proposed.

PMID- 15988744
TI  - HPLC separation of hesperidin and the C-2 epimer in commercial hesperidin samples
      and herbal medicines.
AB  - Hesperidin (2S-form), the flavanone 7-O-glycoside, is the main constituent of
      some Citrus species. The peels of two Citrus species are used as a crude drug,
      Aurantii nobilis pericarpium, in the Japanese Pharmacopoeia and as components in
      Kampo formulae. Thus, HPLC analysis of hesperidin as a marker compound is needed
      for quality control of medicines. Hesperidin was separated from the corresponding
      C-2 epimer by normal-phase HPLC using a chiral column. Moreover, narirutin and
      neohesperidin were also separated from the corresponding C-2 epimer. The analyses
      of commercial hesperidin samples revealed that they contained the C-2 epimer and
      that the relative ratio of hesperidin to the epimer ranged from 92:8 to 59:41.
      The HPLC application to Citrus extracts suggested that naturally occurring
      hesperidin in Citrus has the 2S configuration; however, the dry extracts of
      rikkunshito and chotosan, which are Kampo formulations containing Aurantii
      nobilis pericarpium, were found to contain a considerable amount of the (2R)
      epimer. These data suggest that the decoction process of the formulae partly
      converts hesperidin to the epimer. Because diastereomers differ from each other
      in physicochemical and biological activities, HPLC to separate hesperidin from
      the C-2 epimer should be introduced into the letter of approval for herbal
      medicines.

PMID- 15988745
TI  - Arachnoidal cyst, orofacial dysplasia, poor motor control, and severe language
      delay.

PMID- 15988746
TI  - Another case of Varadi-Papp Syndrome with a molar tooth sign.

PMID- 15988747
TI  - Genetics and women in science.

PMID- 15988748
TI  - Diaphanospondylodysostosis (DSD): confirmation of a recessive disorder with
      abnormal vertebral ossification and nephroblastomatosis.
AB  - We report on four patients from three families, with similar radiological
      findings: absent (or severely delayed) ossification of vertebral bodies and
      associated anomalies. The babies were stillborn or died soon after birth of
      respiratory insufficiency. Two patients are sibs (female and male) born to first
      cousin Malian parents. The two others were non-consanguineous. This perinatally
      lethal entity comprises short neck, short wide thorax, and normally shaped limbs.
      Associated, inconstant anomalies are myelomeningocele, cystic kidneys with
      nephrogenic rests (in the sibs), and cleft palate. Radiologically, the hallmarks
      are absence of ossification of the vertebral bodies and sacrum, abnormal position
      of the vertebral pedicles, which are lamellar and angulated, ribbon-like ribs
      reduced in number, narrow pelvis, upward widening of the iliac wings, and unusual
      tilt of the ischiopubic rami, contrasting with the normal appendicular skeleton.
      Maroteaux briefly described one of the patients in the 2002 edition of "Maladies
      osseuses de l'enfant" and three sibs with similar renal and radiological findings
      were reported in 2003 in this Journal. Combined with the latter cases, these four
      new patients allow delineation of a specific lethal AR syndrome with ossification
      defect of the axial skeleton and renal dysplasia. We propose to name this entity
      diaphanospondylodysostosis.

PMID- 15988749
TI  - Surface-binding autoantibodies to cerebellar neurons in opsoclonus syndrome.
AB  - Childhood opsoclonus-myoclonus syndrome can occur with or without associated
      neuroblastoma. An autoimmune pathogenesis has been discussed for both forms. We
      show here that the majority of children with opsoclonus-myoclonus syndrome
      (10/14) have autoantibodies binding to the surface of isolated rat cerebellar
      granular neurons. In some patients, these antibodies are masked by IgG binding to
      ubiquitous surface antigens, which could be removed by preincubation with the
      nonneuronal control cell line HEK 293. A newly introduced competitive binding
      assay showed that the surface binding is directed against the same autoantigen in
      different patients. Therefore, we hypothesize that opsoclonus-myoclonus syndrome
      may be the result of an autoimmune process against a neuronal surface protein.

PMID- 15988750
TI  - Sex differences in cell death.
AB  - Female patients experience substantial neuroprotection after experimental stroke
      compared with male patients, a finding attributed to the protective effects of
      gonadal hormones. This study examined the response of male- and female-derived
      organotypic hippocampal slices to oxidative and excitotoxic injury. Both oxygen
      and glucose deprivation and N-methyl-D-aspartic acid exposure led to neuronal
      death; however, female-derived cultures sustained less injury than male-derived
      cultures. Cell death after oxygen and glucose deprivation was ameliorated in male
      cultures, but not female cultures, by the addition of 7-nitroindazole, a neuronal
      nitric oxide synthase inhibitor. These studies have relevance to researchers
      investigating neuroprotective agents in mixed sex experiments.

PMID- 15988751
TI  - Saline irrigation does not affect bone formation or fixation strength of
      hydroxyapatite/tricalcium phosphate-coated implants in a rat model.
AB  - Intramembranous bone regeneration is critical to implant fixation. In cementless
      joint replacement (as opposed to cemented joint replacement), saline irrigation
      is not typically performed during surgery so that the osteogenic stimulus
      provided by the marrow is preserved. Several groups are now using the rat marrow
      ablation model to study intramembranous bone regeneration and implant fixation.
      In this model, the marrow contents are mechanically disrupted, and debris is
      often cleared by saline irrigation, a step that appears inconsistent with the
      clinical situation. Furthermore, in contrast to conventional wisdom, it has been
      reported that saline irrigation enhanced bone-implant contact and peri-implant
      bone formation in the rat model (Ishizaka et al. Bone 1996;19:589-594), although
      mechanical fixation of the implant was not investigated. Accordingly, the present
      study was performed to determine if saline irrigation leads to enhanced
      mechanical fixation of implants in the rat model. Forty-eight 400 to 450 g male
      rats were divided equally into two groups. The treatment group, in contrast to
      the control group, received saline irrigation in the ablated medullary canal
      prior to placement of hydroxyapatite/tricalcium phosphate-coated implants. Eight
      animals in each group were killed at 2, 4, or 8 weeks after implantation, at
      which time the specimens were analyzed by micro computed tomography to measure
      bone formation around the implant, followed by a mechanical pull-out test to
      measure the strength of fixation of the implant. As expected, there was increased
      fixation strength over time, but there were no significant differences in peri
      implant bone volume, bone-implant contact, or implant fixation strength between
      the two groups. Thus, we found no effect of saline irrigation on bone formation
      or implant fixation strength in this study in which the implant had an
      osteoconductive coating.

PMID- 15988752
TI  - Porous scaffolds of gelatin-hydroxyapatite nanocomposites obtained by biomimetic
      approach: characterization and antibiotic drug release.
AB  - Gelatin-hydroxyapatite (HA) nanocomposite porous scaffolds were fabricated
      biomimetically, and their feasibility as a drug-delivery carrier for tissue
      regeneration and wound-healing treatments was addressed. The composite sols were
      prepared by the precipitation of HA up to 30 wt % within a gelatin solution with
      the use of calcium and phosphate precursors, and the porous scaffold was obtained
      by casting the sols and further freeze drying. The obtained bodies were
      crosslinked with carbodiimide derivatives to retain chemical and thermal
      integrity. The apatite precipitates were observed to be a poorly crystallized
      carbonate-substituted HA. The nanocomposite scaffolds had porosities of
      approximately 89-92% and exhibited a bimodal pore distribution, that is, the
      macropores (approximately 300-500 microm) of the framework structure, and
      micropores (approximately 0.5-1 microm) formed on the framework surface.
      Transmission electron microscopy (TEM) observation revealed the precipitation of
      highly elongated HA nanocrystals on the gelatin network. The well-developed
      porous structure and organized nanocomposite configurations were in marked
      contrast to the directly mixed gelatin-HA powder conventional composites. For
      drug-release tests, tetracycline, an antibiotic drug, was entrapped within the
      scaffold, and the drug-release profile was examined with processing parameters,
      such as HA amount in gelatin, crosslinking degree, and initial drug addition. The
      drug entrapment decreased with increasing HA amount, but increased with
      increasing crosslinking degree and initial drug addition. The crosslinking of the
      gelatin was the prerequisite to sustaining and controlling the drug releases.
      Compared to pure gelatin, the gelatin-HA nanocomposites had lower drug releases,
      because of their lower water uptake and degradation. All the nanocomposite
      scaffolds released drugs in proportion to the initial drug addition, suggesting
      their capacity to deliver drugs in a controlled manner. Based on the findings of
      the well-developed morphological feature and controlled drug-release profile, the
      gelatin-HA nanocomposite porous scaffolds are suggested to be potentially useful
      for hard-tissue regeneration.

PMID- 15988753
TI  - Angiogenesis, endothelial cell functions, and tumor cell growth in biodegradable
      and nonbiodegradable devices.
AB  - Development of tissue engineering creates multiple potentials for clinical
      treatment and scientific research. Biodegradable collagen matrices have been
      found to support simultaneous autotransplantation of hepatocytes after major
      liver resection. Dynamic angiogenesis in biodegradable devices (BDD) and
      nondegradable devices (NDD) transplanted into the renal subcapsule and
      subcutaneous tissue was measured by the distribution of radiolabeled red blood
      cells and serum albumin. The circulation, microvascular integrity, and capacities
      of endothelial cells (adhesion, proliferation, and migration) were investigated
      within 2 weeks after subcutaneous transplantation of both devices. Patterns of
      tumor cell growth in both devices were morphologically studied. After
      subcutaneous transplantation, significant angiogenesis was noted at 1 week in BDD
      implants and from 2 weeks and on in NDD implants, with an increase in implant
      blood and plasma volumes. Leakage index of radiolabeled albumin in NDD implants
      was significantly higher than in BDD implants, while the leakage index 2 weeks
      after BDD implant was similar to that in subcutaneous tissues. Adhesion,
      proliferation and migration rates of endothelial cells isolated from both devices
      were higher than from subcutaneous tissues. Endothelial proliferation and
      migration rates in BDD implants were significantly higher at 1 week, while in NDD
      at 2 weeks. Tumor cells migrated and grew on the top surface of NDD with a
      flattened shape, while growing within the BDD forming a round mass. Endothelial
      capacities, angiogenetic procedure, and biological and physical characteristics
      of the device contribute to patterns of tumor cell growth in the device.
      Biodegradable collagen matrix with three-dimensional structure is suitable for
      simultaneous transplantation with cells without prevascularization.

PMID- 15988754
TI  - RNT-1 regulation in C. elegans.
AB  - RUNXs are important transcription factors, which are involved in animal
      development and human carcinogenesis. RNT-1, the only homologue of RUNXs, in
      Caenorhabditis elegans (C. elegans) has been identified and viable mutant animals
      of rnt-1 gene have been isolated and characterized recently. Genetic analyses
      using rnt-1 mutants have shown that RNT-1 is regulated by TGFbeta- and Wnt
      signaling pathways in the body size regulation and male tail development. Here,
      we review our current understanding of RNT-1 functions in these signaling
      pathways. Furthermore, future prospects of RNT-1 and BRO-1 studies in C. elegans
      are discussed in this review.

PMID- 15988755
TI  - Simultaneous activation of JAK1 and JAK2 confers IL-3 independent growth on Ba/F3
      pro-B cells.
AB  - JAK1 and JAK2 are tyrosine kinases involved in the regulation of cell
      proliferation, differentiation, and survival. These proteins may play a key role
      in mediating the effects of the cytokine IL-3 on hematopoietic cells. IL-3
      induces tyrosine phosphorylation of both JAK1 and JAK2. However, it is not clear
      whether the activation of JAK1, JAK2, or both is sufficient to confer factor
      independent growth in IL-3 dependent cells. To address this issue, fusion
      proteins CD16/CD7/JAK (CDJAK), comprised of a CD16 extracellular domain, a CD7
      transmembrane domain, and a JAK cytoplasmic region (either a wild-type JAK or a
      dominant negative mutant of JAK) were constructed. We established several Ba/F3
      derivatives that stably overexpress the conditionally active forms of either
      CDJAK1, CDJAK2, or both these fusion proteins. In this study, the
      autophosphorylation of CDJAK1 or CDJAK2 was induced by crosslinking with anti
      CD16 antibody. We demonstrated that, like their wild-type counterparts, CDJAK1
      and CDJAK2 were preassociated with the IL-3 receptor beta and alpha subunits,
      respectively. Furthermore, the simultaneous activation of both CDJAK1 and CDJAK2
      fusion proteins, but not either one alone, led to the tyrosine phosphorylation of
      the IL-3 receptor beta subunit, the activation of downstream signaling molecules,
      including STAT5, Akt, and MAPK, and the conferring of factor-independent growth
      to IL-3-dependent Ba/F3 cells. Coexpression of dominant negative mutants CDJAK1KE
      or CDJAK2KE with wild type CDJAK2 or CDJAK1, respectively, inhibited these
      activation activities. These results suggest that JAK1 and JAK2 must work
      cooperatively and not independently and that their actions are dependent on
      having normal kinase activity to trigger downstream signals leading to IL-3
      independent proliferation and survival of Ba/F3 cells.

PMID- 15988756
TI  - Control of adenovirus packaging.
AB  - The results of studies of Adenovirus have contributed to our basic understanding
      of the molecular biology of the cell. While a great body of knowledge has been
      developed concerning Ad gene expression, viral replication, and effects on the
      infected host, the molecular details of the assembly process of Adenovirus
      particles are largely unknown. In this article, we would like to propose a
      theoretical model for the packaging and assembly of Adenovirus and present an
      overview of the studies that have contributed to our present understanding. In
      particular, we will summarize the molecular details of the process for packaging
      of viral DNA into virus particles and highlight the events in packaging and
      assembly that require further study.

PMID- 15988757
TI  - The bacterial nucleoid: a highly organized and dynamic structure.
AB  - Recent advances in bacterial cell biology have revealed unanticipated structural
      and functional complexity, reminiscent of eukaryotic cells. Particular progress
      has been made in understanding the structure, replication, and segregation of the
      bacterial chromosome. It emerged that multiple mechanisms cooperate to establish
      a dynamic assembly of supercoiled domains, which are stacked in consecutive order
      to adopt a defined higher-level organization. The position of genetic loci on the
      chromosome is thereby linearly correlated with their position in the cell. SMC
      complexes and histone-like proteins continuously remodel the nucleoid to
      reconcile chromatin compaction with DNA replication and gene regulation.
      Moreover, active transport processes ensure the efficient segregation of sister
      chromosomes and the faithful restoration of nucleoid organization while DNA
      replication and condensation are in progress.

PMID- 15988758
TI  - The potential promoter regions on the 5' flank sequence of the mu opioid receptor
      gene in lymphocytes.
AB  - The human mu opioid receptor is known to mediate a variety of physiological and
      pharmacological effects of morphine in many tissues. However, the molecular
      processes that regulate the expression of the mu opioid receptor gene in immune
      cells are not well understood. To study regulatory elements that affect the
      expression of the mu opioid receptor gene in human lymphocytes (LMOR), a 2,278 bp
      fragment of the 5' regulatory region of the mu opioid receptor gene was cloned
      and sequenced from CEM x174 cells. The transcriptional initiation site was mapped
      through a primer extension assay. A series of 5'-deleted plasmids were
      constructed and transiently transfected into cultured CEM x174 cells. The data
      indicated that morphine up-regulated the mRNA level of LMOR in a dose-dependent
      manner, which could be blocked by the opioid receptor antagonist naloxone. Only
      one transcription initiation site (TIS) about 110 bp upstream of the translation
      start codon was identified. The regions from -372 to -253 and -2279 to -1371
      located in the 5' regulatory sequence of the mu opioid receptor gene contained
      enhancer elements, while the regions from -1371 to -968 and -650 to -370
      possessed repressor elements. Those promoter elements were involved in the
      transcriptional regulation of the mu opioid receptor gene. Collectively, this
      data strongly indicates that the expression of the mu opioid receptor gene in
      lymphocytes is subject to the regulation of cis-elements upstream from the TIS.

PMID- 15988759
TI  - A role for plakophilin-1 in the initiation of desmosome assembly.
AB  - Plakophilins (pkp-1, -2, and -3) comprise a family of armadillo-repeat containing
      proteins that are found in the desmosomal plaque and in the nucleus. Plakophilin
      1 is most highly expressed in the suprabasal layers of the epidermis and loss of
      plakophilin-1 expression results in skin fragility-ectodermal dysplasia syndrome,
      which is characterized by a reduction in the number and size of desmosomes in the
      epithelia of affected individuals. To investigate the role of plakophilin-1
      during desmosome formation, we fused plakophilin-1 to the hormone-binding domain
      of the estrogen receptor to create a fusion protein (plakophilin-1/ER) that can
      be activated in cell culture by the addition of 4-hydroxytamoxifen. When
      plakophilin-1/ER was expressed in A431 cells it was incorporated into endogenous
      desmosomes and did not disrupt desmosome formation. A derivative of A431 cells
      (A431D) do not form desmosomes, even though they express all the components
      believed to be necessary for desmosome assembly. Expression and activation of
      plakophilin-1/ER in A431D cells resulted in punctate desmoplakin staining on the
      cell surface. Co-expression of a classical cadherin (N-cadherin) and plakophilin
      1/ER in A431D cells resulted in punctate desmoplakin staining at cell-cell
      borders. These data suggest that plakophilin-1 can induce assembly of desmosomal
      components in A431D cells in the absence of a classical cadherin; however a
      classical cadherin (N-cadherin) is required to direct assembly of desmosomes
      between adjacent cells. The activatable plakophilin-1/ER system provides a unique
      culture system to study the assembly of the desmosomal plaque in culture.

PMID- 15988760
TI  - Extracellular matrix-dependent regulation of angiogenin expression in human
      placenta.
AB  - Knowledge of the rapidly developing hierarchy of controls affecting vascular
      development in placenta is required to understand how the growth factors and
      their receptor-mediated signals actually produce vessels. At the cell biological
      level, these events clearly require stable interactions between the cells, and
      cells with the surrounding ECM. The objective of the study was to understand the
      role of integrins and ECM on the expression and secretion of angiogenin in
      placentas and from trophoblasts in culture. Functionally active term placental
      explant culture and trophoblast cultures were used to demonstrate the
      differential secretion profile of angiogenin and real-time quantitative RT-PCR to
      demonstrate the mRNA expression in the presence or absence of ECM proteins. In
      this study, a significant increase in expression and secretion of angiogenin
      occurred in the presence of vitronectin (VN) and fibronectin (FN). Using antibody
      blocking experiments it was also demonstrated that the angiogenin secretion is
      mediated by placental integrins, alpha(V)beta3 and alpha5beta1. In addition,
      exposure to hypoxic conditions resulted in diminished angiogenin secretion in the
      presence of both ECMs suggesting that angiogenin expression in the presence of
      ECM is modulated by local O2 concentration. In conclusion, this study provides
      evidence for the regulatory role of ECM and integrins on the mRNA expression and
      secretion of angiogenin in human placenta. ECMs may have a pivotal role in
      enhancing secretion of this peptide necessary for placental angiogenesis and
      provides the impetus as additional targets for the control of angiogenesis in
      pathological pregnancy.

PMID- 15988761
TI  - A paradigm for the treatment of prostate cancer bone metastases based on an
      understanding of tumor cell-microenvironment interactions.
AB  - The pliability of cancer cells to mutate into several different phenotypes in an
      attempt to find one that will survive and colonize at the metastatic site is a
      tremendous "hurdle" to overcome in designing novel cancer therapeutics. New
      targets of therapy are essential if we are to effectively overcome the
      evasiveness of cancer. The interaction between the tumor cell and the surrounding
      microenvironment creates a vicious cycle that perpetuates disease survival and
      progression. The future of cancer therapy resides in the ability to focus on the
      recruited and exploited relationships of the cancer cell with the host
      environment. These therapies target cancer cell growth early and interrupt the
      vicious cycle that is created by the tumor cells interacting with bone components
      by inhibiting osteoclasts, osteoblasts, stromal cells, and endothelial cells.
      They alter the bone microenvironment, creating a hostile "soil" that prevents the
      "seed" from developing into bone metastases and represent a potential new
      platform for the development of prostate cancer therapeutics.

PMID- 15988762
TI  - Regulation of parathyroid hypertensive factor secretion by vitamin D3 analogs in
      parathyroid cells derived from spontaneously hypertensive rats.
AB  - Parathyroid hypertensive factor (PHF) is a novel substance secreted by the
      parathyroid gland (PTG), which is elevated in 30-40% of all hypertensive
      patients; specifically, the low-renin subset. However, very little is known about
      the regulation of PHF secretion. Since the classical parathyroid regulator, 1,25
      dihydroxyvitamin D3 (1,25-(OH)2D3), may be elevated concurrent with or preceding
      the development of low-renin hypertension and elevated plasma PHF, we
      hypothesized that 1,25-(OH)2D3 would stimulate PHF release. To test this
      hypothesis, PTG organ and cell cultures, derived from spontaneously hypertensive
      rats (SHR) and the normotensive genetic control Wistar Kyoto (WKY) rats, were
      exposed to various vitamin D3 metabolites and PHF release measured by ELISA. 1,25
      (OH)2D3 rapidly stimulated PHF release with enhanced sensitivity in SHR versus
      WKY cultures indicated by a leftward shift in the dose-response curve, whereas
      24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) had the converse effect. Vitamin D3
      analog "BT," an agonist for the classical nuclear vitamin D receptor
      (1,25VDR(nuc)), was without effect suggesting a 1,25VDR(nuc)-independent
      mechanism and potential involvement of the plasma membrane-bound vitamin D
      receptor (1,25 D3-MARRS). Interestingly, protein expression of the 1,25 D3-MARRS
      was increased in SHR versus WKY parathyroid cells. In conclusion, these results
      support the idea that 1,25-(OH)2D3 may contribute to elevated plasma PHF in the
      SHR.

PMID- 15988763
TI  - Bilateral hippocampal volume reduction in adults with post-traumatic stress
      disorder: a meta-analysis of structural MRI studies.
AB  - Over the last decade a significant number of studies have reported smaller
      hippocampal volume in individuals with symptoms of post-traumatic stress disorder
      (PTSD) relative to control groups, and in some cases hemispheric asymmetries in
      this effect have been noted. However these reported asymmetries have not been in
      a consistent direction, and other well-controlled studies have failed to observe
      any hippocampal volume difference. This paper reports a systematic review and
      meta-analysis of studies in which hippocampal volume was estimated from magnetic
      resonance images in adult patients with PTSD. After applying a variety of
      selection criteria intended to minimize potential confounds in pooled effect-size
      estimates, the meta-analysis included 13 studies of adult patients with PTSD that
      compared the patients to well-matched control groups, for a total of 215 patients
      and 325 control subjects. The studies varied with respect to participant age,
      gender distribution, source of trauma, severity of symptoms, duration of
      disorder, the nature of the control groups, and the methods employed for
      volumetric quantification. Despite these differences, pooled effect size
      calculations across the studies indicated significant volume differences in both
      hemispheres. On average PTSD patients had a 6.9% smaller left hippocampal volume
      and a 6.6% smaller right hippocampal volume compared with control subjects. These
      volume differences were smaller when comparing PTSD patients with control
      subjects exposed to similar levels of trauma, and larger when comparing PTSD
      patients to control subjects without significant trauma exposure. Such
      differences are consistent with the notion that exposure to stressful experiences
      can lead to hippocampal atrophy, although prospective studies would be necessary
      to unambiguously establish such a relationship.

PMID- 15988764
TI  - Dimethyl carbonate in the supercages of NaY zeolite: the role of local fields in
      promoting methylation and carboxymethylation activity.

PMID- 15988765
TI  - Partial protection against Botulinum B neurotoxin-induced blocking of exocytosis
      by a potent inhibitor of its metallopeptidase activity.
AB  - Clostridium botulinum neurotoxins (BoNTs) cause botulism, which is characterized
      by a flaccid paralysis, through inhibition of acetylcholine release by peripheral
      cholinergic nerve terminals. This is due to the zinc metallopeptidase activity of
      the neurotoxin, cleaving one component (synaptobrevin for BoNT/B) of the
      exocytosis machinery. Yet, there are no specific agents able to control the
      peptidase-related effects of BoNT/B. We recently developed the first compounds to
      inhibit this enzymatic activity in the nanomolar range. Here we report that two
      of our best inhibitors prevent the BoNT/B-induced cleavage of native
      synaptobrevin on synaptic vesicles, and partially inhibit the suppression of
      [3H]noradrenaline release from synaptosomes that is caused by BoNT/B. These
      results were obtained at micromolar concentrations, consistent with the measured
      inhibitory potency of these inhibitors on the native toxin. These compounds
      provide a new way to possibly prevent and/or to control the neurotoxin effects of
      botulinum.

PMID- 15988766
TI  - Shotgun cloning and heterologous expression of the patellamide gene cluster as a
      strategy to achieving sustained metabolite production.

PMID- 15988767
TI  - Effect of ArcA and FNR on the expression of genes related to the oxygen
      regulation and the glycolysis pathway in Escherichia coli under microaerobic
      growth conditions.
AB  - Escherichia coli has several elaborate sensing mechanisms for response to the
      availability of oxygen and the presence of other electron acceptors. The adaptive
      responses are coordinated by a group of global regulators, which include the one
      component Fnr protein, and the two-component Arc system. To quantitate the
      contribution of Arc and FNR dependent regulation under microaerobic conditions,
      the gene expression pattern of the fnr the arcA and arcB regulator genes, and the
      glycolysis related genes in a wild-type E. coli, an arcA mutant, an fnr mutant,
      and a double arcA, fnr mutant, in glucose limited cultures and different oxygen
      concentrations was studied in chemostat cultures at steady state using QRT-PCR.
      It was found that ArcA has a negative effect on fnr expression under microaerobic
      conditions. Moreover, the expression levels of the FNR regulated genes, yfiD and
      frdA, were higher in cultures of the arcA mutant strain compared to the wild
      type. These imply that a higher level of the FNR regulator is in the activated
      form in cultures of the arcA mutant strain compared to the wild-type during the
      transition from aerobic to microanaerobic growth. The results also show that the
      highest expression level of aceE, pflB, and adhE were obtained in cultures of the
      arcA mutant strain under microaerobic growth while higher levels of ldhA
      expression were obtained in cultures of the arcA mutant strain and the arcA, fnr
      double mutant strain compared to the wild-type and the fnr mutant strain. While
      the highest expression of adhE and pflB in cultures of the arcA mutant strain can
      explain the previous report of high ethanol flux and flux through pyruvate
      formate lyase (PFL) in cultures of this strain, the higher level of ldhA
      expression was not sufficient to explain the trend in lactate fluxes. The results
      indicate that lower conversion of pyruvate to acetyl-CoA is the main reason for
      high fluxes through lactate dehydrogenase (LDH) in cultures of the arcA, fnr
      double mutant strain.

PMID- 15988768
TI  - Use of water to evaluate hydrophobicity of organically-modified xerogel enzyme
      supports.
AB  - Silica xerogels are a new class of materials suitable for the immobilization of
      enzymes for various applications including biotransformations and biosensors. The
      physicochemical properties of xerogels, such as hydrophobicity, can be
      manipulated by the introduction of organically-modified silicates. This allows
      the immobilization matrix to be engineered to suit the enzyme and its
      application. Interfacial activation of lipase is a phenomenon in which the enzyme
      displays increased activity when it is bound to a hydrophobic interface. Lipase
      was entrapped in organically-modified xerogels in which the hydrophobicity of the
      enzyme support was modulated by the selection of different alkyltrimethoxysilane
      co-precursors and the ratio in which they were combined with tetramethyl
      orthosilicate. Interaction between the enzyme support and water was investigated
      with two methods to quantitatively assess the hydrophobicity of the entrapment
      matrix. The contact angle formed between the xerogel and water was used to
      determine hydrophobicity on a macroscopic level. Temperature-controlled water
      desorption was used to determine hydrophobicity on a microscopic level. Both
      methods were suitable for quantitatively discriminating between hydrophobic and
      hydrophilic materials. Further, the hydrophobicity of the enzyme support
      influenced the hydrolytic activity of the entrapped lipase under non-aqueous
      conditions. The specific activity of lipase increased only when entrapped in
      xerogels which could be classified as hydrophobic materials, that is with contact
      angles greater than 90 degrees or hydrophobicity values as determined by water
      desorption greater than 0.65.

PMID- 15988769
TI  - CO oxidation catalyzed by supported gold: cooperation between gold and
      nanocrystalline rare-earth supports forms reactive surface superoxide and
      peroxide species.

PMID- 15988770
TI  - Oxidative cyclization of diols derived from 1,5-dienes: formation of enantiopure
      cis-tetrahydrofurans by using catalytic osmium tetroxide; formal synthesis of (+)
      cis-solamin.

PMID- 15988771
TI  - Quasi-continuous combined scattered light and fluorescence measurements: a novel
      measurement technique for shaken microtiter plates.
AB  - A novel quasi-continuous on-line measuring technique for shaken microtiter plates
      is presented. Light scattering as well as intracellular and/or protein
      fluorescence (e.g. NADH, YFP) is measured during the shaking procedure, thus
      allowing a process monitoring of 96 different simultaneous cultures in a
      microtiter plate. In contrast to existing measurement techniques, the shaking
      process does not have to be stopped to take the measurements, thus avoiding the
      corresponding interruption of the cultures' oxygen supply and any unpredictable
      effects on the cultures. Experiments were conducted with E. coli in LB, TB, and
      MOPS minimal medium and V. natriegens in modified LB and TB media. Intensity
      curves of scattered light and NADH fluorescence were used to distinguish
      different lag phases, growth velocities, or inoculation densities. Data from this
      new method corresponded well to the off-line measured optical densities and to
      the oxygen transfer rates of cultures run in simultaneously conducted shake flask
      experiments at equivalent oxygen transfer capacities. With the aid of yellow
      fluorescence protein fused to interleukin-6 the optimal induction time of an
      expressing E. coli strain could be determined by on-line monitoring of product
      formation. Thus, this measuring technique enables the researcher to evaluate and
      to discriminate different cultures on a screening level and to improve screening
      conditions, process development and scale-up.

PMID- 15988772
TI  - Probing the mechanism of the palladium-catalyzed addition of organoboronic acids
      to allenes in the presence of AcOH by ESI-FTMS.

PMID- 15988773
TI  - Diversity oriented one-pot synthesis of complex macrocycles: very large steroid
      peptoid hybrids from multiple multicomponent reactions including bifunctional
      building blocks.

PMID- 15988774
TI  - The Co ligand field: a key parameter in photomagnetic CoFe prussian blue
      derivatives.

PMID- 15988775
TI  - Ligand-induced formation of an adamantanoid hexanuclear (pi-Allyl)Pd(II)(mu3
      Hydroxo) cluster stacked as hydrogen-bonded double strands.

PMID- 15988776
TI  - Elucidation of the reaction mechanism for the palladium-catalyzed synthesis of
      vinyl acetate.

PMID- 15988777
TI  - Protonated isobutene in zeolites: tert-butyl cation or alkoxide?

PMID- 15988778
TI  - Highly water-soluble thermally responsive poly(thiophene)-based brushes.

PMID- 15988779
TI  - An electrolytic system that uses solid-supported bases for in situ generation of
      a supporting electrolyte from acetic acid solvent.

PMID- 15988780
TI  - Mechanism of remote conjugate addition of a lithium organocuprate to a
      polyconjugated carbonyl compound.

PMID- 15988781
TI  - Highly fluorescent self-coordinated phthalocyanine dimers.

PMID- 15988782
TI  - Temperature-induced inversion of nanoparticle-stabilized emulsions.

PMID- 15988784
TI  - Prenatal diagnosis of echogenic lung: evolution and outcome.
AB  - OBJECTIVES: Despite the feasibility of detecting lung lesions by antenatal
      ultrasound, there are problems in correlating the prenatal diagnosis with the
      final histology and in predicting the outcome. In order to better describe these
      factors, we reviewed the outcome of fetuses that had been diagnosed with
      echogenic lung in a referral fetal medicine unit. METHODS: We searched the
      database of a tertiary fetal medicine unit for all cases of fetal echogenic lung
      seen since 1994 and studied the maternal and neonatal records found. RESULTS:
      There were 48 cases of echogenic lung diagnosed at a median gestational age of 21
      (range, 19-29) weeks, including 43 (90%) cases of congenital cystic adenomatoid
      malformation (CCAM) and 5 (10%) of pulmonary sequestration (PS). The evolution of
      the fetal abnormality after diagnosis was: in 22 (45.8%) cases the lesion
      disappeared; in 17 (35.5%) cases the lesion remained stable and six (12.5%) cases
      became severe. Three (6%) women underwent termination of pregnancy. The lesions
      were equally distributed between the two sides of the thorax. Mediastinal shift
      was associated with a threefold increase in the possibility of clinical
      deterioration (17% vs. 5%), and the disappearance of the lesion was twice as
      likely to occur when the lesion was classified as microcystic as when it was
      macrocystic (67% vs. 36%). Features of hydrops were found in 9 (21%) fetuses and
      in six (13%) cases progressed and resulted in intrauterine or neonatal death.
      Sixty-four percent of cases with lesions that disappeared during the pregnancy
      had an abnormal computed tomography (CT) scan, and the prenatal diagnosis
      correlated with histology in 36% of these cases. Of the cases in which the
      lesions remained stable, 70.5% had an abnormal CT scan and the prenatal diagnosis
      correlated with the histology in 67% of the cases. CONCLUSIONS: Prenatally
      diagnosed echogenic lung has a good prognosis in the absence of hydrops. The
      ability to correctly assess echogenic lung lesions and the need for surgery by
      prenatal ultrasound is limited.

PMID- 15988783
TI  - Bone marrow and blood plasma levels of IL-8 in aplastic anemia and their
      relationship with disease severity.
AB  - Interleukin-8 (IL-8), a CXC chemokine, is also a potent inhibitor of
      myelopoiesis, the hematopoietic process that is severely impaired in aplastic
      anemia (AA). To elucidate its role in the disease, we have investigated levels of
      IL-8 by quantitative enzyme-linked immunosorbent assay in bone marrow and
      peripheral blood plasma of 27 AA patients and in the marrow of 16 controls and
      blood of 20 controls. Significantly increased levels of IL-8 were observed in the
      marrow and blood of patients as compared to controls (470.4 +/- 549.6 vs. 37.5 +/
      30.3; P < 0.0001) and (247.3 +/- 286.3 vs. 7.9 +/- 5.5; P < 0.0001),
      respectively. Among the patients, the IL-8 levels were higher in patients with
      severe AA than those with nonsevere AA in the marrow (568.8 +/- 586.9 vs. 126.3
      +/- 102.5; P < 0.005) as well as in the blood (296.6 +/- 305.5 vs. 75.0 +/- 84.4;
      P < 0.008) plasma. The marrow and blood of 74% (20/27) of the patients had
      increased levels of IL-8 compared to 12% (2/16; P < 0.001) and 10% (2/20, P <
      0.001) of the controls, respectively. These results suggest that IL-8 may have an
      important role in the pathogenesis of AA.

PMID- 15988785
TI  - Early prenatal diagnosis of endocardial fibroelastosis.

PMID- 15988786
TI  - Two-dimensional and three-dimensional ultrasound imaging of suburethral slings.
AB  - OBJECTIVE: Suburethral slings have become the most commonly performed anti
      incontinence procedures in many developed countries. Three types of implant
      account for the majority of such surgery in Australia: tensionless vaginal tape
      (TVT), suprapubic arc procedure (SPARC) and intravaginal slingplasty (IVS). The
      aim of this study was to determine differences in position and mobility of these
      implants, and to determine whether such differences explain variations in
      clinical outcome. METHODS: In a prospective randomized controlled trial, 195
      women were randomized to TVT (n = 67), IVS (n = 64) or SPARC (n = 64). Thirteen
      women were excluded from the study due to incomplete preoperative data. Of the
      remaining 182 women, 146 (50 TVT, 48 IVS, 48 SPARC) were seen between 2 and 23
      months after their procedure (80%). After an interview, two-dimensional (2D) and
      three-dimensional (3D) pelvic floor ultrasound was performed. 3D-volume analysis
      was carried out on a computer with the help of proprietary software (GE Kretz 4D
      View). Assessors of ultrasound data were blinded against group allocation.
      RESULTS: There were no significant differences in subjective cure/improvement of
      stress or urge incontinence or overall subjective cure/improvement. Symptoms,
      including those of voiding dysfunction, did not vary between groups. All tapes
      could be imaged by ultrasound. TVT and SPARC were highly echogenic, with the
      SPARC generally flatter and of wider weave. The IVS seemed narrower and less
      echogenic. Tape position and mobility were similar, with a trend towards greater
      distances between tape and symphysis pubis and greater horizontal tape mobility
      in the SPARC group. CONCLUSIONS: The three types of suburethral sling, namely
      TVT, SPARC and IVS, investigated using 2D and 3D ultrasound, have comparable
      short-term clinical and anatomical outcomes.

PMID- 15988787
TI  - Prenatal detection of a fetal parotid tumor.

PMID- 15988788
TI  - Kinetic investigation of the effect of the amino acid side chains in the
      selective acidolysis of N-acyl-N,alpha,alpha-trialkyl glycine amides.
AB  - Accurate kinetic measurements of the rate constants for the acidolysis of five N
      acetyl-N-(4-methoxybenzyl)-alpha,alpha-trialkyl glycine cyclohexyl amides in TFA
      were performed at 25 degrees C and the reactions monitored by HPLC. In all cases
      the results were consistent with a first order behaviour with respect to the
      substrate. No direct correlation was obtained with these data between the rate
      constant values and structure, but a good correlation coefficient was obtained
      when a multiple regression analysis was applied by taking advantage of a Taft
      equation using appropriate polar and steric substituent parameters. In a plot of
      the values observed for log k against those calculated by this equation all five
      points fell very close to the line of perfect correlation. The calculated
      sensitivity coefficients to polar and steric contributions were used to discuss
      the experimental results and showed that the acidolysis were comparatively less
      affected by steric effects than expected.

PMID- 15988789
TI  - Enzymatic polymerization behavior using cellulose-binding domain deficient
      endoglucanase II.
AB  - A mutant enzyme, EGII(core), in which the cellulose-binding domain was deleted
      from endoglucanase II from Trichoderma viride, was expressed in yeast, and the
      secreted enzyme was examined for the enzymatic polymerization to obtain
      artificial cellulose. EGII(core) polymerized beta-cellobiosyl fluoride to afford
      crystalline cellulose of type II. Comparison of the polymerization behavior of
      EGII(core) with that of EGII revealed the following: i) the crystalline product
      obtained with EGII(core) was stable in the polymerization solution, although the
      product was readily hydrolyzed in the presence of EGII; ii) the turnover number
      of EGII(core) was as high as that of EGII; iii) EGII(core) produced highly
      crystalline cellulose. EGII(core) is therefore advantageous for enzymatic
      polymerization.

PMID- 15988790
TI  - Enzymatic transformation of bacterial polyhydroxyalkanoates into repolymerizable
      oligomers directed towards chemical recycling.
AB  - The enzymatic transformation into an oligomer was carried out with the objective
      of developing the chemical recycling of bacterial polyesters. Poly(R-3
      hydroxyalkanoate)s (PHAs), such as poly[(R-3-hydroxybutyrate)-co-12%(R-3
      hydroxyhexanoate)] and poly[(R-3-hydroxybutyrate)-co-12%(R-3-hydroxyvalerate)],
      were degraded by granulated Candida antarctica lipase B immobilized on
      hydrophilic silica (lipase GCA) in a diluted organic solvent at 70 degrees C. The
      degradation products were cyclic oligomers having a molecular weight of a few
      hundreds. The obtained cyclic oligomer was readily repolymerized by the same
      lipase (lipase GCA) to produce the corresponding polyester in a concentrated
      solution. The cyclic oligomer was copolymerized with epsilon-caprolactone using
      lipase to produce the corresponding terpolymers having an Mw of 21,000. This is
      the first example of the enzymatic chemical recycling of bacterial PHAs using
      lipase. Poly(R-3-hydroxybutyrate) [P(3HB)] was also degraded into the linear-type
      R-3HB monomer to trimer by P(3HB)-depolymerase (PHBDP) in phosphate buffer at 37
      degrees C. The degradation using PHBDP required a longer reaction time compared
      with the lipase-catalyzed degradation in organic solvent. The monomer composition
      of the oligomer depended on the origin of the PHBDP. The R-3HB monomer was
      predominately produced by PHBDP from Pseudomonas stutzeri, while the R-3HB dimer
      was produced by PHBDP from Alcaligenes faecalis T1. Repolymerization of these
      oligomers by lipase in concentrated organic solvent produced a relatively low
      molecular-weight P(3HB) (e.g., Mw=2,000). Degradation of P(3HB) by lipase in
      organic solvent into repolymerizable cyclic oligomer and degradation of P(3HB) by
      PHBDP in buffer into hydroxy acid type R-3HB dimer.

PMID- 15988791
TI  - Multicentre validation study of sentinel node biopsy for staging in breast
      cancer.
AB  - BACKGROUND: The aim of this study was to validate sentinel node biopsy for
      axillary staging after the initial learning phase, and to analyse factors
      associated with false-negative biopsies. METHODS: Some 675 patients, who had
      standard sentinel node biopsy followed by level I and II axillary clearance in
      one of 20 hospitals in Sweden and were operated on by 36 different surgeons, were
      recruited prospectively. RESULTS: The overall detection rate was 94.5 per cent.
      It varied between surgeons but was not influenced by the number of operations per
      surgeon. Moreover, it was lower among older patients. The overall false-negative
      rate was 7.7 per cent. This rate was not affected by patient age, tumour
      histological type or Elston grade, but was increased in patients with multifocal
      tumours. Some 21 per cent of patients with a multifocal tumour diagnosed on
      postoperative histopathological analysis had a false-negative biopsy compared
      with 5.6 per cent of those with unifocal tumours (P = 0.004). CONCLUSION:
      Sentinel node biopsy was shown to be a reliable method for axillary staging of
      unifocal breast tumours.

PMID- 15988792
TI  - Risk factors associated with ileal pouch-related fistula following restorative
      proctocolectomy.
AB  - INTRODUCTION: Pouch-related fistula occurs in 5-10 per cent of patients after
      restorative proctocolectomy. The present study identified risk factors associated
      with the development of such fistulas. METHODS: Data on preoperative and
      postoperative risk factors were recorded from 1965 patients who underwent
      restorative proctocolectomy in a single tertiary centre between 1983 and 2001.
      Cox regression analysis was used to identify independent predictors of pouch
      perineal, pouch-abdominal wall and pouch-vaginal fistula during follow-up.
      RESULTS: Median patient follow-up was 4.1 (range 0-19) years. By 15 years' follow
      up, pouch-vaginal fistulas had occurred in 44 women (5.2 per cent). The
      prevalence of ileal pouch-perineal and pouch-abdominal wall fistula was 3.6 per
      cent (70 patients) and 1.5 per cent (30 patients) respectively. Independent
      predictors of pouch-related fistula identified by multivariate analysis were
      diagnosis of indeterminate colitis or Crohn's disease (hazard ratio (HR) 1.28 (95
      per cent confidence interval (c.i.) 1.00 to 1.65) and 1.73 (95 per cent c.i. 1.07
      to 3.48) respectively versus ulcerative colitis or familial adenomatous
      polyposis), previous anal pathology (HR 3.43 (95 per cent c.i. 2.43 to 4.84) and
      4.02 (95 per cent c.i. 1.27 to 12.77) respectively for perineal abscess and
      fistula in ano versus no previous anal pathology), abnormal anal manometry (HR
      4.29 (95 per cent c.i. 2.33 to 7.91)), patient sex (HR 0.74 (95 per cent c.i.
      0.58 to 0.95) for men versus women) and pelvic sepsis (HR 3.79 (95 per cent c.i.
      2.48 to 5.79)). CONCLUSION: This study suggests that Crohn's disease and the
      clinical signs that favour the diagnosis of Crohn's disease may contribute to the
      development of pouch-related fistula.

PMID- 15988793
TI  - Primary endocrine tumours of the liver.
AB  - BACKGROUND: In patients with hepatic endocrine tumours, a primary neoplasm is not
      always found elsewhere despite extensive investigations, raising the possibility
      that the hepatic lesion is the primary tumour. The aim of this study was to
      assess the incidence, characteristics and prognosis of patients with primary
      hepatic endocrine tumours. METHODS: Patients with histologically confirmed
      hepatic endocrine tumours identified since 1993 were reviewed. All those with no
      primary tumour identified by computed tomography of the thorax, abdomen and
      pelvis, upper and lower digestive endoscopy, duodenopancreatic endoscopic
      ultrasonography or somatostatin receptor scintigraphy (SRS) were included.
      Clinical and tumour characteristics were assessed retrospectively. RESULTS: Of
      393 patients with digestive endocrine tumours, 17 (seven men; median age 55
      (range 26-69) years) had hepatic endocrine tumours without evidence of an
      extrahepatic primary lesion either at diagnosis or during a median follow-up of
      43 (range 12-108) months. Ten patients had multiple and seven had single tumours.
      The tumours were non-functional in 13 patients and well differentiated in 14
      patients. SRS was positive in the liver in 11 patients. Curative resection was
      performed in seven. Overall actuarial survival rates were 100, 69 and 51 per cent
      at 1, 3 and 5 years respectively. Only poor differentiation was associated with
      an unfavourable outcome (relative risk 20.8; P < 0.001). CONCLUSION: Primary
      hepatic endocrine tumours were identified in almost 5 per cent of patients with
      digestive endocrine tumours. Poor differentiation was the only factor associated
      with unfavourable outcome.

PMID- 15988794
TI  - Subtotal parathyroidectomy with thymectomy for autonomous hyperparathyroidism
      after renal transplantation.
AB  - BACKGROUND: There is currently no consensus on the operation that should be
      performed in patients with tertiary hyperparathyroidism (HPT) after renal
      transplantation. METHODS: : A retrospective analysis of 70 patients with tertiary
      HPT who underwent subtotal parathyroidectomy with transcervical thymectomy was
      performed. RESULTS: Mean (s.d.) follow-up was 5.6(5.0) years. Mean (s.d.)
      glomerular filtration rate (GFR) at follow-up was 42(29) ml/min and was less than
      30 ml/min in 26 patients (37 per cent), 30-60 ml/min in 25 (36 per cent) and more
      than 60 ml/min in 19 (27 per cent). One patient had persistent disease and was
      cured after reoperation. No patient was hypercalcaemic. Four patients (6 per
      cent) with a GFR below 30 ml/min had a parathyroid hormone (PTH) level more than
      four times the normal value without any signs or symptoms of secondary HPT. One
      patient (1 per cent) was hypocalcaemic and two (3 per cent) were normocalcaemic,
      with undetectable or below-normal PTH levels while receiving oral vitamin D and
      calcium medication. CONCLUSION: Systematic subtotal parathyroidectomy associated
      with thymectomy is effective in treating most renal transplant recipients with
      tertiary HPT and also minimizes the recurrence of HPT in patients with declining
      renal function.

PMID- 15988795
TI  - Integration of the heart rhythmogenesis levels: heart rhythm generator in the
      brain.
AB  - We propose that along with the intracardiac pacemaker, a generator of cardiac
      rhythm exists in the central nervous system--in the efferent structures of the
      cardiovascular center of the medullar oblongata. Signals in the medulla oblongata
      arise as a result of the hierarchic interaction of the brain structures. Neural
      signals originating there in the form of bursts of impulses conduct to the heart
      along the vagus nerves and after interaction with cardiac pacemaker structures,
      cause generation of the cardiac pulse in exact accordance with the frequency of
      "neural bursts". The intrinsic cardiac rhythm generator (the sinus node) is a
      life-sustaining factor that maintains the heart pumping function when the central
      nervous system is in a stage of deep inhibition, (e.g., under anesthesia or
      during unconsciousness). The brain generator is the factor that provides heart
      adaptive reactions in behaving organism. The integration of the two levels of
      rhythmogenesis in the brain and heart provides reliability and functional
      perfection of the cardiac rhythm generation system in the whole organism.

PMID- 15988796
TI  - Selecting parameters for phase space reconstruction of the electrocorticogram
      (ECoG).
AB  - The selection of parameters for phase space reconstruction of empirically
      observed data has been a source of criticism when estimating the correlation
      dimension (D2) from observed data rather than from the solution of differential
      equations, when analyzing noisy and potentially non-stationary signals, such as
      the electroencephalogram (EEG). The largely arbitrary selection of the time-delay
      reconstruction (T) of temporal dynamics, and for the embedding (M) of these
      series, has been widely criticized. This study adopted an analytic and
      statistical framework within which the scaling behavior of D2 with respect to T
      and M, could be examined over five data lengths (N = 4096, 8192, 12288, 16384,
      and 20480) over an 8 x 8 grid of cat EEG. It was found that D2 was invariant over
      all data lengths only within a very narrow T range (T = 10-16) for M = 4. A
      statistically significant T by M interaction was found using multiple analysis of
      variance, with D2 being highly correlated over T as a function of M. Finally, an
      examination of phase-randomized surrogates indicated that statistically
      significant differences existed between EEG and phase-randomized surrogates over
      all data lengths, with time delays (T = 10-16), indicating that the D2 for EEG is
      phase-dependent when it is invariant with respect to data length. The
      implications of these findings are discussed with respect to current models of
      ECoG generation, and their implication with respect to the integration in the
      brain.

PMID- 15988797
TI  - Emerging concepts of brain function.
AB  - For over 40 years, since I first obtained evidence for nonsynaptic diffusion
      neurotransmission (most scientists call it Volume Transmission), I have been
      convinced that we scientists were ignoring organizational dynamics other than the
      mechanistic synaptic organization of the brain. For many years it was an uneasy
      feeling, since I was aware there are so many avenues to explore in brain
      function. I have wondered how much we scientists have ignored, in our quest to
      understand how the brain really works, due to our efforts to "be scientific". In
      addition to the difficulty of understanding how the brain functions, how could we
      even begin to explore the human experience? In this paper I will first discuss
      some emerging concepts of brain function. I will then comment on the development
      of concepts that have been a part of my own research experience.

PMID- 15988798
TI  - Synaptic inhibition and pathologic hyperexcitability through enhanced neuron
      astrocyte interaction: a modeling study.
AB  - Recently, upregulation of metabotropic glutamate receptors (mGluRs) on
      hippocampal astrocytes in epileptic tissues has become part of the etiology of
      epilepsy and suggests the involvement of astrocytes in the disease. Through
      computational modeling, we have shown in previous work that upregulated mGluRs on
      astrocytes can give rise to positive feedback in closed loop neuron-astrocyte
      circuits with epilepsy-type spontaneous neuronal spiking. In this paper we
      further quantify the necessary degree of upregulation of astrocytic mGluRs,
      relate it to recent clinical and experimental studies, and address through
      computational modeling the role of synaptic inhibition through interneurons in
      this form of hyperexcitability. We conclude that inhibitive circuitry cannot tame
      this form of hyperexcitability.

PMID- 15988799
TI  - Rallian "equivalent" cylinders reconsidered: comparisons with literal
      compartments.
AB  - In Rall's "equivalent" cylinder morphological-to-electrical transformation,
      neuronal arborizations are reduced to single unbranched core-conductors. The
      conventional assumption that such an "equivalent" reconstructs the electrical
      properties of the fibers it represents was tested directly; electrical properties
      and responses of "equivalent" cylinders were compared with those of their literal
      branch constituents for fibers with a single symmetrical bifurcation. The
      numerical solution methods were validated independently by their accurate
      reconstruction of the responses of an analog circuit configured with
      compartmental architecture to solve the cable equation for passive fibers with a
      symmetrical bifurcation. In passive fibers, "equivalent" cylinders misestimated
      the spatial distribution of voltage amplitudes and steady-state input resistance,
      partly due to the lack of axial current bifurcation. In active fibers with a
      single propagating action potential, the spatial distributions of point-to-point
      conduction velocity values (measured in meters/second) for a literal branch point
      differed significantly from those of their "equivalent" cylinders. "Equivalent"
      cylinders also underestimated the diameter-dependent delay in propagation through
      the branch point and branches, due to the larger "equivalent" diameter.
      Corrections to the "equivalent" cylinder did not reconcile differences between
      "equivalent" and literal models. However, "equivalent" and literal branch fibers
      had the same (a) steady-state resistance "looking into" an isolated symmetrical
      branch point and (b) geometry-independent point-to-point propagation velocity
      when measured in space constants per millisecond except within +/-1 space
      constant from the geometrical inhomogeneity. In summary, Rall's "equivalent"
      cylinders did not accurately reconstruct all passive or active
      electrophysiological properties and responses of their literal compartments. For
      the modeling of individual neurons, the requirement of single-branch resolution
      is discussed.

PMID- 15988800
TI  - Event based self-supervised temporal integration for multimodal sensor data.
AB  - A method for synergistic integration of multimodal sensor data is proposed in
      this paper. This method is based on two aspects of the integration process: (1)
      achieving synergistic integration of two or more sensory modalities, and (2)
      fusing the various information streams at particular moments during processing.
      Inspired by psychophysical experiments, we propose a self-supervised learning
      method for achieving synergy with combined representations. Evidence from
      temporal registration and binding experiments indicates that different cues are
      processed individually at specific time intervals. Therefore, an event-based
      temporal co-occurrence principle is proposed for the integration process. This
      integration method was applied to a mobile robot exploring unfamiliar
      environments. Simulations showed that integration enhanced route recognition with
      many perceptual similarities; moreover, they indicate that a perceptual hierarchy
      of knowledge about instant movement contributes significantly to short-term
      navigation, but that visual perceptions have bigger impact over longer intervals.

PMID- 15988801
TI  - Efficacy of oral etidronate for skeletal diseases in Japan.
AB  - Etidronate is an oral bisphosphonate compound that is known to reduce bone
      resorption through the inhibition of osteoclastic activity. The efficacy of
      etidronate for involutional (postmenopausal and senile) and glucocorticoid
      induced osteoporosis, as well as that for other skeletal diseases, was reviewed
      in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2
      weeks about every 3 months) increases the lumbar bone mineral density (BMD) in
      patients with involutional osteoporosis and prevents incident vertebral fractures
      in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar
      BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic
      patients after stroke are prevented, and the lumbar BMD is possibly increased,
      preventing fragile fractures in adult patients with osteogenesis imperfecta type
      I. Furthermore, proximal bone resorption around the femoral stem is reduced and
      some complications may be prevented in patients who undergo cementless total hip
      arthroplasty. Oral etidronate treatment may also help to transiently relieve
      metastatic cancer bone pain followed by a decrease in abnormally raised bone
      resorption in patients with painful bone metastases from primary cancer sites,
      such as the lung, breast and prostate. Thus, oral etidronate treatment is
      suggested to be efficacious for osteoporosis, as well as other skeletal diseases
      associated with increased bone resorption, in Japanese patients. Randomized
      controlled trials needed to be conducted on a large number of patients to confirm
      these effects.

PMID- 15988802
TI  - Interest groups' influence over drug pricing policy reform in South Korea.
AB  - In 1999, the Korean government made a drug pricing policy reform to improve the
      efficiency and transparency of the drug distribution system. Yet, its policy
      formation process was far from being rational. Facing harsh resistance from
      various interest groups, the government changed its details into something
      different from what was initially investigated and planned. So far, little
      evidence supports any improvement in Korea's drug distribution system. Instead,
      the new drug pricing policy has deteriorated Korea's national health insurance
      budget, indicating a heavier economic burden for the general public. From Korea's
      experience, we may draw some lessons for the future development of a better
      health care system. As a society becomes more pluralistic, the government should
      come out of authoritarianism and thoroughly prepare in advance for resistance to
      reform, by making greater efforts to persuade strong interest groups while
      informing the general public of potential benefits of the reform. Additionally,
      facing developing civic groups, the government should listen but not rely too
      much on them at the final stage of the policy formation. Many of the civic groups
      lack expertise to evaluate the details of policy and tend to act in a somewhat
      emotional way.

PMID- 15988803
TI  - Development of a structural model explaining medication compliance of persons
      with schizophrenia.
AB  - The purpose of this study was to develop and test a structural model explaining
      medication compliance of schizophrenia. From a review of the literature, a
      hypothetical model was developed based on the conceptual framework of the Health
      Belief Model with medication knowledge, symptom severity and social support as
      the exogenous variables, and perceived benefits, perceived barriers, substance
      use and medication compliance as the endogenous variables. Data was collected at
      various mental health facilities, including psychiatric outpatient clinics of
      general hospitals and community mental health centers, between March and May,
      2001. A structured questionnaire was used by one- on- one interviews to collect
      data on 208 schizophrenic patients. Well established measurement instruments,
      with confirmed reliability, were used to assess each method variable. As a result
      of covariance structural analysis, the hypothetical model was found not to fit
      the empirical data well, so a parsimonious model was adopted after modifying the
      model. The final model was able to explain the 33 % medication compliance.
      Medication knowledge, social support and perceived benefits had significant
      effects on medication compliance. The findings of this study address the
      importance of medication education and social support to promote medication
      compliance. It is also suggested that various education programs and support
      groups are needed to enhance medication compliance.

PMID- 15988804
TI  - Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice.
AB  - Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the
      suppression of Th1 cells or the activation of Th2 cells has been regarded as a
      plausible immunologic intervention for the prevention of type 1 diabetogenesis in
      a rodent model. CpG ODN is an immunostimulatory sequence primarily present in
      bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1
      cell activator, which has been clinically applied to cancer, allergy and
      infectious disease. Recently, there was a promising report of that CpG ODN
      administration suppressed the development of type 1 diabetes in NOD mice by
      inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG
      ODN on NOD mice is controversial. Thus, two studies were serially undertaken with
      various kinds of CpG motif to find a more optimal sequence and administration
      method. In the first study, CpG ODN was vaccinated four times and pancreatic
      inflammation and the quantity of serum insulin subsequently evaluated. In the
      second study, the amounts of IFN gamma and IL-4 in sera were measured as
      representative cytokines of Th1 and Th2 cells, respectively. As a result,
      vaccination or continuous injection of CpG ODN failed to show a preventive effect
      on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had
      no affect on the result. CpG ODN also consistently showed affect on the
      pancreatic pathology. The productions of IFN gamma and IL-4 were detected only in
      the K and D type CpG ODN administration groups. Comparison of the two cytokines
      leads to the conclusion that CpG ODN generated a Th1-weighted response in both
      study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine
      milieu, which can overcome the genetically determined phenotype of NOD mice.
      Given these results, it was concluded that the immunotherapeutic application of
      CpG ODN on Type 1 diabetes had clear limitations.

PMID- 15988805
TI  - Effectiveness of real-time quantitative PCR compare to repeat PCR for the
      diagnosis of Charcot-Marie-Tooth Type 1A and hereditary neuropathy with liability
      to pressure palsies.
AB  - The majority of cases of Charcot-Marie-Tooth type 1A (CMT1A) and of hereditary
      neuropathy with a liability to pressure palsies (HNPP) are the result of
      heterozygosity for the duplication or deletion of peripheral myelin protein 22
      gene (PMP22) on 17p11.2. Southern blots, pulsed-field gel electrophoresis (PFGE),
      fluorescence in situ hybridization (FISH) and polymorphic marker analysis are
      currently used diagnostic methods. But they are time-consuming, labor-intensive
      and have some significant limitations. We describe a rapid real- time
      quantitative PCR method for determining gene copy number for the identification
      of DNA duplication or deletion occurring in CMT1A or HNPP and compare the results
      obtained with REP-PCR. Six patients with CMT1A and 14 patients with HNPP
      [confirmed by Repeat (REP)-PCR], and 16 patients with suspicious CMT1A and 13
      patients with suspicious HNPP [negative REP-PCR], and 15 normal controls were
      studied. We performed REP-PCR, which amplified a 3.6 Kb region (including a 1.7Kb
      recombination hotspot), using specific CMT1A-REP and real-time quantitative PCR
      on the LightCycler system. Using a comparative threshold cycle (Ct) method and
      beta -globin as a reference gene, the gene copy number of the PMP22 gene was
      quantified. The PMP22 duplication ratio ranged from 1.35 to 1.74, and the PMP22
      deletion ratio from 0.41 to 0.53. The PMP22 ratio in normal controls ranged from
      0.81 to 1.12. All 6 patients with CMT1A and 14 patients with HNPP confirmed by
      REP-PCR were positive by real-time quantitative PCR. Among the 16 suspicious
      CMT1A and 13 suspicious HNPP with negative REP-PCR, 2 and 4 samples,
      respectively, were positive by real-time quantitative PCR. Real-time quantitative
      PCR is a more sensitive and more accurate method than REP-PCR for the detection
      of PMP22 duplications or deletions, and it is also faster and easier than
      currently available methods. Therefore, we believe that the real-time
      quantitative method is useful for diagnosing CMT1A and HNPP.

PMID- 15988806
TI  - The involvement of multipotential progenitor cells in Mooren's ulcer.
AB  - The aim of this study was to assess the involvement of multipotential progenitor
      cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining
      techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who
      underwent lamellar keratectomy. Immunohistochemical staining patterns were
      analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and a-SMA. Strong
      positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens,
      especially in the superficial stroma. A few weakly expressed CD34 stroma cells
      were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1
      could be found. CD45RO positive T cells were found to have infiltrated in
      Mooren's ulcer. The immunostaining pattern of VEGF and a- SMA was closely
      correlated with the degree of expression and the number of CD34 positive cells.
      Bone marrow-derived multipotential progenitor cells may be involved in the
      pathogenesis of Mooren's ulcer by synergizing with other factors to amplify
      autoimmune destructive reactions and to contribute to the regeneration process.
      Specific therapeutic strategies that target the role of these cells in the
      disease are warranted.

PMID- 15988807
TI  - Ocular motility disturbances in orbital wall fracture patients.
AB  - It is difficult to identify the exact cause of ocular motility disturbances in
      orbital wall fracture patients. By performing CT and ocular motility tests before
      and after surgery, this study analyzes the functions of the extraocular muscles
      and determines correlations between the results. Between February 2001 and
      January 2003, 45 eyes of 45 patients with orbital wall fractures, whose medical
      records could be traced back at least 6 months, underwent surgical repair in our
      hospital. All variables were analyzed using the independent t-test, paired t
      test, and Chi-square test. There was no significant difference in the location
      and degree of fracture and the incarceration pattern of 6 patients who had
      moderate or severe diplopia, and of the remaining patients 6 months after
      surgery. However, in the case of diplopia, the sum of ocular motility limitation
      was 5.67 +/- 4.18, and the degree of extraocular motility disturbance was 3.67 +/
      2.42 before surgery. When there was no diplopia, the sum of ocular motility
      limitation was 1.13 +/- 1.38, and the degree of extraocular motility disturbance
      was 1.08 +/- 1.16 (p < 0.005, independent t-test). Ocular movement was
      successfully recovered by surgical reduction within 3 weeks from trauma.
      Postoperative ocular motility disturbance was more related to various ocular
      motility test results than CT findings. Ocular motility disturbances can remain
      after surgery if ocular motility limitation and extraocular motility disturbance
      are significant after trauma. Additional studies on the various tests to examine
      functions of extraocular muscles are required to identify and analyze the exact
      cause of ocular motility disturbance.

PMID- 15988808
TI  - Contrast sensitivity function of sound eye after occlusion therapy in the
      amblyopic children.
AB  - To verify the changes of mesopic and photopic contrast sensitivity function of
      sound eye whose visual acuity was kept the same after occlusion therapy in the
      amblyopic children. Fourteen sound eyes of amblyopic children (mean; 7.67 years;
      S.D., 1.50 years) who kept their visual acuity the same after the occlusion
      therapy were tested. The children had 6 hours of part-time patch therapy for 3
      months prior to this examination. Among 14 amblyopic children, 8 were anisometric
      and 6 were strabismic amblyopes. Using the visual capacity analyzer which
      measures the minimal contrast level at from low to high spatial frequencies, the
      contrast sensitivity of sound eye was measured, under both photopic and mesopic
      condition, before and after 3 months of occlusion therapy. Comparing the contrast
      sensitivity of sound eye after the occlusion therapy to that before the
      occlusion, there was no statistical difference in photopic condition. When it
      comes to mesopic condition, the contrast sensitivity decreased at the
      intermediate spatial frequency level (3-13 c.p.d, p=0.028) after the occlusion
      therapy. The occlusion caused statistically significant decrease in mesopic
      contrast sensitivity, when the visual acuity was not changed after the occlusion
      therapy. It may indicate that mesopic contrast sensitivity can be considered as a
      useful tool for early detection of hidden occlusion amblyopia.

PMID- 15988809
TI  - Cortical margining capabilities of fins associated with ventral cervical spine
      instrumentation.
AB  - Fins incorporated into the design of a dynamic cervical spine implant have been
      employed to enhance axial load- bearing ability, yet their true biomechanical
      advantages, if any, have not been defined. Therefore, the goal of this study was
      to assess the biomechanical and axial load-bearing contributions of the fin
      components of the DOC ventral cervical stabilization system. Eighteen fresh
      cadaveric thoracic vertebrae (T1-T3) were obtained. Three test conditions were
      devised and studied: Condition A (DOC implants with fins were placed against the
      superior endplate and bone screws were not inserted); Condition B (DOC implant
      without fins was placed and bone screws were inserted); and Condition C (DOC
      implant with fins were placed against the superior endplate and bone screws were
      inserted). Specimens were tested by applying a pure axial compressive load to the
      superior platform of the DOC construct, and load-displacement data were
      collected. Condition C specimens had the greatest stiffness (459 +/- 80 N/mm) and
      yield load (526 +/- 168 N). Condition A specimens were the least stiff (266 +/-
      53 N/mm), and had the smallest yield loads (180 +/- 54 N). The yield load of
      condition A plus condition B was approximately equal to that of condition C, with
      condition A contributing about one-third and condition B contributing two-thirds
      of the overall load-bearing capacity. Although the screws alone contributed to a
      substantial portion of axial load-bearing ability, the addition of the fins
      further increased load-bearing capabilities.

PMID- 15988810
TI  - Neurologic recovery according to early magnetic resonance imaging findings in
      traumatic cervical spinal cord injuries.
AB  - The aim of this study was to determine the usefulness of early magnetic resonance
      imaging findings in predicting neurologic recovery at or below the injured level
      in traumatic cervical spinal cord injuries. Thirty patients with traumatic
      cervical spinal cord injuries were included. All of the patients received a
      magnetic resonance imaging and a neurologic examination in the emergency room,
      within 7 days of injury and at 6 months following the injury. To quantify
      neurologic recovery below the injured level, we modified clinical scales,
      particularly the motor ratio and the sensory ratio. We used the neurologic level
      to quantify recovery around the injured level. We assessed neurologic recovery
      according to MRI patterns and lesion extents. The pure hemorrhagic MRI pattern
      was not observed. In edematous and mixed types, the improvement of neurologic
      levels was not significantly different. The motor ratio and sensory ratio
      improved significantly more in edematous type patients than in mixed type
      patients. Based on MRI lesion extent, the improvement of neurologic levels was
      not significantly different, and motor ratio and sensory ratio improved
      significantly more in those with one or two segments involved than in those with
      more than two segments involved. In conclusion, early MRI pattern and lesion
      extent after traumatic cervical spinal cord injury may provide important
      information to help predict neurologic recovery, especially below the injured
      level.

PMID- 15988811
TI  - Usefulness of bone metabolic markers in the diagnosis of bone metastasis from
      lung cancer.
AB  - Bone metastasis is common in lung cancer patient and the diagnosis of bone
      metastasis is usually made by using imaging techniques, especially bone
      scintigraphy. However, the diagnostic yield from bone scintigraphy is limited.
      The aim of this study is to assess the clinical usefulness of urinary
      pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), urinary
      deoxypyridinoline (DPD), and serum alkaline phosphatase (ALP) in the assessment
      of bone metastasis in patients with lung cancer. Urinary NTx, DPD, and serum ALP
      were measured in 151 lung cancer patients (33 with and 118 without bone
      metastasis). Lung cancer patients with bone metastasis had a higher urinary
      excretion of NTx and DPD, and a higher serum ALP than those without bone
      metastasis. NTx had a better receiver operating characteristic (ROC) curve than
      DPD and ALP, since the areas under the ROC curve were 0.82, 0.79, and 0.71,
      respectively. Although correlation coefficients among NTx, DPD and ALP were
      significantly positive (p < 0.005), the strongest relationship was appeared
      between NTx and DPD (R = 0.616). In conclusion, our results showed the utility of
      the new bone markers in detecting bone metastasis and suggested that measurement
      of urinary NTx was valid diagnostic method of bone metastasis from lung cancer.

PMID- 15988812
TI  - Pretreatment with ursodeoxycholic acid (UDCA) as a novel pharmacological
      intervention in hepatobiliary scintigraphy.
AB  - The purpose of this volunteer study was to investigate whether pretreatment with
      UDCA before the administration of (99m)Tc DISIDA affects the biliary excretion of
      the DISIDA, and whether it can shorten the total imaging time. Ten young, healthy
      volunteers (eight males, two females, mean age: 26.3 +/- 2.1 years) participated
      in the study. Hepatobiliary scintigraphies were performed twice per volunteer
      within three days, for the control and the UDCA-pretreated studies. In the
      control study, the gallbladder (GB) was observed first in four cases and the
      intestine was observed first in another four cases; in contrast, in the UDCA
      challenge study, the GB was observed first in eight cases. The quantitative
      results for the factors related to the GB differed significantly between the
      control and challenge studies. When the subjects were pretreated with UDCA, the
      time duration until visualization of the GB was shortened, and the maximum
      activity of the GB became more intense. In conclusion, UDCA pretreatment before
      hepatobiliary scintigraphy can shorten the total imaging time for evaluating
      functional obstructions of the cystic duct and increase the specificity of the
      process.

PMID- 15988813
TI  - Comparison of rifaximin and lactulose for the treatment of hepatic
      encephalopathy: a prospective randomized study.
AB  - Rifaximin has been reported to be effective for the treatment of hepatic
      encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is
      effective for the treatment of HE in Koreans, therefore we conducted a open-label
      prospective randomized study to evaluate the efficacy of rifaximin versus
      lactulose in Korean patients. Fifty-four patients with liver cirrhosis and
      hepatic encephalopathy were enrolled. Thirty-two patients were randomized to
      receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before
      and at the end of treatment, gradation of blood ammonia, flapping tremor, mental
      status, number connection test (NCT) were performed and estimation of HE indexes
      determined. Both rifaximin and lactulose were effective in the majority of
      patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor,
      mental status, and NCT was significantly improved by rifaximin and lactulose, and
      the post- treatment levels of these measures were similar for the rifaximin and
      lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p =
      0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with
      rifaximin complained of abdominal pain, which was easily controlled. There was no
      episode of renal function impairment in either treatment group. Rifaximin proved
      to be as safe and as effective as lactulose for the treatment of Korean patients
      with hepatic encephalopathy.

PMID- 15988814
TI  - The relationship between maximal urethral closure pressure and functional
      urethral length in anterior vaginal wall prolapse patients according to stage and
      age.
AB  - MUCP (Maximal urethral closure pressure) is known to be increased in patients
      with vaginal wall prolapse due to the mechanical obstruction of the urethra.
      However, urethral function following reduction has not yet been completely
      elucidated. Predicting postoperative urethral function may provide patients with
      important, additional information prior to surgery. Thus, this study was
      performed to evaluate the relationship between MUCP and functional urethral
      length (FUL) according to stage and age in anterior vaginal wall prolapse
      patients. 139 patients diagnosed with anterior vaginal wall prolapse at Yonsei
      University Medical College (YUMC) from March 1999 to May 2003 who had underwent
      urethral pressure profilometry following reduction were included in this study.
      The stage of pelvic organ prolapse (POP) was determined according to the
      dependent portion of the anterior vaginal wall (Aa, Ba). (By International
      Continence Society's POP Quantification system) Patients were divided into one of
      four age groups: patients in their 40s (n = 13), 50s (n = 53), 60s (n = 54), and
      70 and over (n = 16). No difference in MUCP was found between the age groups. The
      FUL of patients in their 40s was shorter than that of patient's in their 50s and
      60s. Patients were also divided into stages: stage II (n = 35), stage III (n =
      76), and stage IV (n = 25). No significant difference in MUCP was found according
      to stage and FUL. However, a significant difference was noted between stage III
      and IV as stage IV was longer. Anterior vaginal wall prolapse is known to affect
      urethral function due to prolapse itself, but according to our study, prolapse
      itself did not alter urethral function. This suggests that, regardless of age and
      stage, prolapse corrective surgery does not affect the urethral function.

PMID- 15988815
TI  - Prostate-specific antigen, digital rectal examination and transrectal
      ultrasonography: a meta-analysis for this diagnostic triad of prostate cancer in
      symptomatic korean men.
AB  - We conducted a meta-analysis using results from the Korean literature to
      determine whether prostate-specific antigen (PSA) or digital rectal examination
      (DRE) or transrectal ultrasonography (TRUS) provides a better diagnostic outcome
      for possible prostate cancer patients. An extensive literature search of MedRIC
      database et al. (1980 to 2003) was performed using the medical subject headings
      "PSA", "DRE", "TRUS" and "prostate cancer". Of the 108 articles that we
      retrieved, 13 studies (2,029 subjects) were selected for this meta-analysis. The
      criteria for quality evaluation were as follows: the study subjects must have
      been compared clinically for suspected prostate cancer, and the articles must
      have included individual data about sensitivity and specificity for this
      diagnostic triad based on the biopsy results as a reference standard. For the
      quantitative meta-analysis process the Hasselblad method was utilized. The pooled
      sensitivity and specificity for a PSA level greater than 4ng/mL were 91.3 % and
      35.9 %, respectively; and those for a PSA level greater than 10ng/mL were 77.3 %
      and 67.5 %, respectively; and those for DRE were 68.4 % and 71.5 %, respectively;
      and those for TRUS were 73.6 % and 61.3 %, respectively. According to the results
      in a fixed effect model for PSA criteria, the estimates of d for PSA4 and PSA10
      were 0.8517 [95 % confidence interval (CI): 0.6694, 1.0340] and 1.0996 (95 % CI:
      0.9459, 1.2534), respectively. Also, according to the results using a random
      effect model for both DRE and TRUS criteria, the estimates of d for DRE and TRUS
      were 0.8398 (95 % CI: 0.7169, 0.9627) and 0.8002 (95 % CI: 0.6714, 0.9289),
      respectively. The detection rate for combination testing of PSA, DRE and TRUS for
      the diagnosis of prostate cancer jumped further to 68.3 % or to 76.8 %. In
      conclusion, this study suggests that this diagnostic triad for prostate cancer
      was noneffective when they were used separately. Therefore, we recommend that the
      urologists should use PSA together with DRE and TRUS for the primary diagnosis of
      prostate cancer in men with lower urological symptoms.

PMID- 15988816
TI  - An unusual case of spontaneous remission of Hodgkin's disease after a single
      cycle of COPP-ABV chemotherapy followed by infectious complications.
AB  - Advanced Hodgkin's disease is usually treated with six or more cycles of
      combination chemotherapy. Spontaneous regression of the cancer is very rarely
      reported in patients with Hodgkin's disease. We present an unusual case of a
      patient with Hodgkin's disease who experienced complete remission with a single
      cycle of chemotherapy, followed by pneumonia. The case was a 36-year-old man
      diagnosed with stage IVB mixed cellularity Hodgkin's disease in November 2000.
      After treatment with one cycle of COPP-ABV (cyclophosphamide, vincristine,
      procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) chemotherapy
      without bleomycin, the patient developed interstitial pneumonia and was cared in
      the intensive care unit (ICU) for two months. Follow-up chest computerized
      tomography (CT), performed during the course of ICU care, revealed markedly
      improved mediastinal lymphomatous lesions. Furthermore, follow-up whole body CT
      and 18-fluorodeoxyglucose positron emission tomography showed complete
      disappearance of the lymphomatous lesions. Four years later, the patient is well
      and without relapse. This report is followed by a short review of the literature
      on spontaneous regression of Hodgkin's disease. To the best of our knowledge,
      this is the first case report of spontaneous remission of Hodgkin's disease in
      Korea.

PMID- 15988817
TI  - Nosocomial Oral Myiasis by Sarcophaga sp. in Turkey.
AB  - We present a case of oral myiasis in a 15-year-old boy with tuberculosis
      meningitis. The diagnosis was based on the visual presence of wriggling larvae
      about 1 cm in size and on the microscopic features of the maggots, especially
      those relating to stigmatic structures. The larvae were identified as third-stage
      larvae of Sarcophaga sp.

PMID- 15988818
TI  - Spontaneous splenic rupture in a hemodialysis patient.
AB  - Spontaneous splenic rupture (SSR) in a patient undergoing hemodialysis has been
      described as an extremely rare and potentially fatal complication. We report here
      spontaneous splenic rupture in a 52-year-old woman undergoing regular
      hemodialysis for end-stage renal disease (ESRD). She complained of colicky
      abdominal pain in the left upper quadrant area and dizziness when she assumed an
      upright posture. Her vital signs revealed low blood pressure and tachycardia,
      which was suggestive of hypovolemic shock. Abdomen CT scan showed splenic
      hematoma and hemoperitoneum. However, she had no history of any event triggering
      the splenic rupture. An exploratory laparotomy showed a ruptured spleen and an
      emergency splenectomy was performed. We suggest that spontaneous spleen rupture
      may be attributed to uremic coagulopathy and heparin-induced coagulopathy.

PMID- 15988819
TI  - Primary idiopathic chylopericardium associated with cervicomediastinal cystic
      hygroma.
AB  - Chylopericardium is a rare clinical entity in which chylous fluid accumulates in
      the pericardial cavity. We report a case of primary idiopathic chylopericardium
      associated with multiple, small cervicomediastinal cystic hygromas occurring in
      an asymptomatic 43-year-old woman with no history of trauma, thoracic surgery,
      malignancy, infection or tuberculosis. Echocardiography showed a large amount of
      pericardial effusions and pericardial fluid analysis revealed inappropriately
      elevated triglyceride. We did not demonstrate communication between the thoracic
      duct and the pericardial sac by lymphangiography and chest computed tomography.
      She successfully responded to 30 days of continuous pericardial drainage and 15
      days of a medium-chain triglyceride diet after 30 days of total parenteral
      nutrition. Follow-up echocardiography 6 months after treatment commencement
      showed a minimal reaccumulation of pericardial fluid without symptom. We conclude
      that if a patient is asymptomatic and can well tolerate daily life, surgery
      including pericardiectomy or ligation of the thoracic duct is not necessarily
      required.

PMID- 15988821
TI  - Bibliography. Current world literature. Paediatric and neonatal infections.

PMID- 15988820
TI  - Dieulafoy's lesion of jejunum: presenting small bowel mass and stricture.
AB  - Dieulafoy's lesion is an uncommon cause of gastrointestinal bleeding. Hemorrhage
      occurs through mucosal erosion from an abnormally dilated submucosal artery.
      Although Dieulafoy's lesion is usually located in the stomach, it may occur
      anywhere in the gastrointestinal tract. We report here on a case of jejunal
      Dieulafoy's lesion presenting as a mass and short segment stricture on CT and
      enteroclysis.

PMID- 15988822
TI  - COMPARE/Radiology, an interactive Web-based radiology teaching program evaluation
      of user response.
AB  - RATIONALE AND OBJECTIVES: The aim of this study is to assess user benefits of
      COMPARE/Radiology, a highly interactive World Wide Web-based training program for
      radiology, as perceived by its users. MATERIALS AND METHODS: COMPARE/Radiology
      (http://www.idr.med.uni-erlangen.de/compare.htm), an interactive training program
      based on 244 teaching cases, was created by the authors and made publicly
      available on the Internet. An anonymous survey was conducted among users to
      investigate the composition of the program's user base and assess the acceptance
      of the training program. In parallel, Web access data were collected and analyzed
      using descriptive statistics. RESULTS: The group of responding users (n = 1370)
      consisted of 201 preclinical medical students (14.7%), 314 clinical medical
      students (22.9%), 359 residents in radiology (26.2%), and 205 users of other
      professions (14.9%). A majority of respondents (1230; 89%) rated the
      interactivity of COMPARE/Radiology as good or excellent. Many respondents use
      COMPARE/Radiology for self-study (971; 70%) and for teaching others (600; 43%).
      Web access statistics show an increase in number of site visits from 1248 in
      December 2002 to 4651 in April 2004. CONCLUSION: Users appreciate the benefits of
      COMPARE/Radiology. The interactive instructional design was rated positively by
      responding users. The popularity of the site is growing, evidenced by the number
      of network accesses during the observation period.

PMID- 15988823
TI  - Progression of dystonia in complex regional pain syndrome.

PMID- 15988824
TI  - Gene symbol: JAG1. Disease: Alagille syndrome.

PMID- 15988825
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15988826
TI  - Gene symbol: IRF6. Disease: Van der Woude syndrome.

PMID- 15988827
TI  - Gene symbol: MLH1. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15988828
TI  - Gene symbol: GLB1. Disease: GM1 gangliosidosis infantile.

PMID- 15988829
TI  - Gene symbol: HMBS. Disease: Porphyria, acute intermittent.

PMID- 15988830
TI  - BhairPred: prediction of beta-hairpins in a protein from multiple alignment
      information using ANN and SVM techniques.
AB  - This paper describes a method for predicting a supersecondary structural motif,
      beta-hairpins, in a protein sequence. The method was trained and tested on a set
      of 5102 hairpins and 5131 non-hairpins, obtained from a non-redundant dataset of
      2880 proteins using the DSSP and PROMOTIF programs. Two machine-learning
      techniques, an artificial neural network (ANN) and a support vector machine
      (SVM), were used to predict beta-hairpins. An accuracy of 65.5% was achieved
      using ANN when an amino acid sequence was used as the input. The accuracy
      improved from 65.5 to 69.1% when evolutionary information (PSI-BLAST profile),
      observed secondary structure and surface accessibility were used as the inputs.
      The accuracy of the method further improved from 69.1 to 79.2% when the SVM was
      used for classification instead of the ANN. The performances of the methods
      developed were assessed in a test case, where predicted secondary structure and
      surface accessibility were used instead of the observed structure. The highest
      accuracy achieved by the SVM based method in the test case was 77.9%. A maximum
      accuracy of 71.1% with Matthew's correlation coefficient of 0.41 in the test case
      was obtained on a dataset previously used by X. Cruz, E. G. Hutchinson, A.
      Shephard and J. M. Thornton (2002) Proc. Natl Acad. Sci. USA, 99, 11157-11162.
      The performance of the method was also evaluated on proteins used in the '6th
      community-wide experiment on the critical assessment of techniques for protein
      structure prediction (CASP6)'. Based on the algorithm described, a web server,
      BhairPred (http://www.imtech.res.in/raghava/bhairpred/), has been developed,
      which can be used to predict beta-hairpins in a protein using the SVM approach.

PMID- 15988831
TI  - Pcleavage: an SVM based method for prediction of constitutive proteasome and
      immunoproteasome cleavage sites in antigenic sequences.
AB  - This manuscript describes a support vector machine based method for the
      prediction of constitutive as well as immunoproteasome cleavage sites in
      antigenic sequences. This method achieved Matthew's correlation coefficents of
      0.54 and 0.43 on in vitro and major histocompatibility complex ligand data,
      respectively. This shows that the performance of our method is comparable to that
      of the NetChop method, which is currently considered to be the best method for
      proteasome cleavage site prediction. Based on the method, a web server,
      Pcleavage, has also been developed. This server accepts protein sequences in any
      standard format and present results in a user-friendly format. The server is
      available for free use by all academic users at the URL
      http://www.imtech.res.in/raghava/pcleavage/ or
      http://bioinformatics.uams.edu/mirror/pcleavage/.

PMID- 15988832
TI  - A girl with abnormal head and eye movements: Joubert syndrome (2005:3b).
AB  - We describe a mentally retarded patient with developmental delay, abnormal head
      and eye movements with suspected blindness and episodes of abnormal breathing.
      Subsequent CT and MRI were performed to reach to the final diagnosis. The
      clinical history and the imaging findings were classical for Joubert syndrome.

PMID- 15988833
TI  - Faulty heart devices force some scary decisions; patients weigh risks of
      replacing unit through surgery.

PMID- 15988834
TI  - MN: waking & dressing pts. before shift starts: fired employee denied
      unemployment benefits.

PMID- 15988835
TI  - Congress scrutinizes hospitals' tax-exempt status.

PMID- 15988836
TI  - [A rare case of combination of ischemic stroke and arteriovenous lung aneurism in
      a patient with hereditary hemorrhagic telangiectasia].
AB  - A case of 38-year old man with typical symptoms of Randu-Osler disease, having
      lung bilateral vascular malformation as well as the signs of brain blood flow
      lesion (ischemic stroke) is reported. A genesis of the cerebral vascular signs is
      discussed.

PMID- 15988837
TI  - [Methods in the treatment of rheumatoid arthritis with Chinese herbal drugs:
      experimental study on collagen-induced arthritis].

PMID- 15988838
TI  - A new species of Acanthobothrium (Cestoda: Tetraphyllidea: Onchobothriidae) from
      the ocellate river stingray, Potamotrygon motoro (Chondrichthyes:
      Potamotrygonidae), in Argentina.
AB  - Examination of the spiral intestines of 44 freshwater stingrays, Potamotrygon
      motoro, from tributary rivers of the Parana River in Argentina, allowed for the
      collection of specimens of an undescribed species of Acanthobothrium.
      Acanthobothrium ramiroi n. sp. can be distinguished from all other congeners by
      the combination of the following characters: asymmetrical hooks (medial and
      lateral hooks conspicuously different in size and form, with axial prong of
      medial hooks stouter than abaxial prong), hook size (total length of medial hooks
      up to 242 microm, total length of lateral hooks up to 239 microm), bothridia not
      fused to the scolex proper at posterior ends, worm size (51-84 mm long), and the
      presence of a conspicuous vaginal sphincter. The new species is different from
      all other species of Acanthobothrium in freshwater potamotrygonids, except
      Acanthobothrium terezae, in having conspicuous asymmetrical hooks. The main
      differences that allow for the distinction between A. ramiroi and A. terezae
      include hook size, the way the bothridia are attached to the scolex proper, and
      the shape of the older gravid segments. The discovery of a new species of
      Acanthobothrium from a potamotrygonid extends our understanding of the diversity
      of the genus in freshwater stingrays in South America.

PMID- 15988839
TI  - Challenges and opportunities for pathogen detection using DNA microarrays.
AB  - DNA microarrays offer the potential for simultaneous detection of many pathogens
      that are of interest to homeland security, public health, medicine, and
      veterinary diagnostics. These tools are best suited for detecting the presence or
      absence of genetic sequences characteristic of specific pathogens, but
      microarrays are poorly suited for determining pathogen viability, and current
      methods provide only limited potential for pathogen enumeration. Two basic
      strategies have been described for pathogen detection: using enzymatic
      amplification to generate targets for interrogation with a microarray, or using
      direct interrogation of DNA or RNA without pre-amplification. Multiplex PCR has
      the advantage of a high degree of sensitivity and specificity, but associated
      microarrays are necessarily limited in scope. PCR-independent, whole-genome
      amplification eliminates biases inherent in PCR amplification and can accommodate
      more extensive microarrays, but assay sensitivity is compromised and these
      methods are probably of limited use when testing tissue samples. Direct
      hybridization of DNA or RNA provides the least bias in gene detection, but also
      the lowest level of analytic sensitivity. Ultimately, cost and limited sample
      throughput make it unlikely that planar microarrays will play a significant role
      in future pathogen detection schemes. Alternative microarray formats such as bead
      arrays, however, may circumvent the cost and throughput limitations and permit us
      to apply what we have learned from planar microarrays to develop robust pathogen
      detection systems. Assay validation and sample preparation will continue to be
      significant challenges for these detection systems.

PMID- 15988840
TI  - A role for school health personnel in supporting children and families following
      childhood injury.

PMID- 15988841
TI  - Proceedings of the 16th Annual Workshop on Eosinophils in Allergy and Related
      Diseases. June 26, 2004. Tokyo, Japan.

PMID- 15988842
TI  - Abstracts of ISCO 2005 (International Society for Cellular Oncology), Belfast,
      Northern Ireland, 5-8 April 2005.

PMID- 15988843
TI  - Abstracts of the 28th Annual Conference on Shock. Marco, Island, Florida, USA, 4
      7 June 2005.

PMID- 15988844
TI  - Abstracts of the 1st North American Chapter Meeting of the International Society
      for Peritoneal Dialysis (ISPD). Chicago, Illinois, USA, April 29-May 1, 2005.

PMID- 15988845
TI  - Abstracts of the 40th Congress of the European Society for Surgical Research
      (ESSR). Konya, Turkey, May 25-28, 2005.

PMID- 15988847
TI  - How does an accident become an experiment? Secret science and the exposure of the
      public to biological warfare agents.

PMID- 15988846
TI  - Risk versus risk: decision-making dilemmas of drug regulation in the United
      States and Germany.

PMID- 15988848
TI  - Contemporary science communication as a world of political invention.

PMID- 15988849
TI  - Abstracts of the 65th Scientific Sessions of the American Diabetes Association.
      San Diego, California, USA, 10-14 June 2005.

PMID- 15988850
TI  - Abstracts of the 12th International Congress of Biorheology and the 5th
      International Conference on Clinical Hemorheology. Chongqing, China, May 30-June
      3, 2005.

PMID- 15988851
TI  - Orthopaedic proceedings: 2003, 2004.

PMID- 15988852
TI  - [Abstracts of the 25th International Congress of the Association of
      Dermatologists of the French Speaking Community. Aoste, Italy, 22-25 June 2005].

PMID- 15988853
TI  - Abstracts of the 20th Annual Meeting of the European Association of
      Cardiothoracic Anaesthesiologists.

PMID- 15988854
TI  - [Concept of self and love in psychopathology].

PMID- 15988855
TI  - International Conference on Harmonisation; guidance on Q5E Comparability of
      Biotechnological/Biological Products Subject to Changes in Their Manufacturing
      Process; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "Q5E Comparability of Biotechnological/Biological Products
      Subject to Changes in Their Manufacturing Process." The guidance was prepared
      under the auspices of the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH). The purpose
      of the guidance is to provide principles for assessing the comparability of
      biotechnological/biological products before and after changes are made in the
      manufacturing process for the drug substance or drug product. The guidance is
      intended to assist in the collection of relevant technical information that
      serves as evidence that the manufacturing process changes will not have an
      adverse impact on the quality, safety, and efficacy of the drug product.

PMID- 15988856
TI  - [Prevention of old age syndrome and becoming bed-ridden due to accidental
      falling].

PMID- 15988857
TI  - [Views of care management in health care, care giving and social welfare for the
      aged].

PMID- 15988858
TI  - Proceedings of the 4th Asia-Pacific Regional Meeting of the International Society
      for Neonatal Screening. October 17-19, 2001, Mandaluyong City, Philippines.

PMID- 15988859
TI  - Pharmacovigilance--Current and Future Challenges. Abstracts of the International
      Society of Pharmacovigilance annual conference. Dublin, Ireland, 6-8 October
      2004.

PMID- 15988860
TI  - Abstracts of the 8th Conference on Progress in Etiopathogenesis of Seizures.
      Lublin, Poland, 21 November 2003.

PMID- 15988861
TI  - Regulating preimplantation genetic diagnosis: the pathologization problem.

PMID- 15988862
TI  - Assessing the viability of a substantive due process right to in vitro
      fertilization.

PMID- 15988863
TI  - [Studies on delirium].

PMID- 15988864
TI  - [Drug therapy for aged patients with psychosomatic symptoms].

PMID- 15988865
TI  - [Community strategies for rehabilitation in senile dementia].

PMID- 15988866
TI  - New HIPAA complaint and enforcement procedures.

PMID- 15988867
TI  - Leadership retention strategies.

PMID- 15988868
TI  - The predictable swarm: staying on top of radiology's cyclical staffing "bug".
AB  - Partners HealthCare System in Boston, MA, took some progressive and bold steps to
      address the recent staffing shortages in radiology. By addressing the shortage at
      the system level versus the individual hospital level, Partners was able to
      successfully recruit and support more than 80 new radiologic technologists from
      initial interest through graduation in 2 years. The recruitment effort helped
      reduce the utilization of temporary/agency personnel that cost the system more
      than dollar 6 million in 2001. The system utilized a multi-disciplinary team of
      professionals at many levels in the organization to achieve significant results
      in a relatively short period of time. Further, the organization channeled all
      available resources, including a grant from the US Department of Labor (DOL). The
      Boston Private Industry Council (BPIC), a local organization well known to the
      Partners HealthCare community benefits and human resources departments, managed
      the DOL grant. At least 64 of the first 80 graduates have accepted positions
      within Partners HealthCare radiology departments. The organization has further
      populated a database of more than 1,000 interested candidates, some of whom are
      currently in school and preparing for a future career in radiology, hopefully
      within the Partners HealthCare System. Partners HealthCare has managed to
      maintain a diversity rate at over 25% people of color by utilizing targeted
      recruiting efforts. Partners plans to continue to offer scholarships and other
      methods of support and career laddering for radiologic technologists in order to
      continue to meet staffing needs well in to the future. Partners HealthCare
      developed and implemented a "grow your own" strategy, and the system's leaders
      hold the philosophy that workforce development is a long-term investment
      requiring a flexible, permanent plan to stay ahead of the clinical staffing
      curve.

PMID- 15988869
TI  - Identifying elements of job satisfaction to improve retention rates in
      healthcare.
AB  - According to the American Hospital Association, by the year 2010, the United
      States will need 1,000,000 qualified nurses to care for patients, an additional
      75,000 licensed radiologic technologists, and several other ancillary medical
      staff employees. A number of health professionals question why there is such a
      significant shortage--especially considering that many facilities; are
      implementing cost initiatives and insurance companies are decreasing the length
      of patient hospital stays. One specific factor may not be fully appreciated:
      Although the length of stay is decreasing,the acuity level of the patient is
      increasing. The number and types of available opportunities also contribute to
      the staffing shortage. Hospitals and healthcare facilities are now working
      diligently to address the crisis and answer that one very important question: How
      can they keep employees satisfied and willing commit long-term to the
      organization? This review focuses on identifying those key variables of job
      satisfaction that will lead to long-term retention of healthcare workers,
      including money, work environment, performance feedback, advancement
      opportunities, group cohesion, and relationships with management. It also
      discusses the effects of demographic characteristics such as age and gender on
      job satisfaction.

PMID- 15988870
TI  - Guess what? You do make a difference!

PMID- 15988871
TI  - PET coding.

PMID- 15988872
TI  - Make your RIS/PACS work ... for you.

PMID- 15988873
TI  - Multislice CT: 64 slices and beyond.
AB  - Since the first introduction of 4-slice multislice computed tomography (MSCT)
      more than 6 years ago, MSCT imaging has achieved widespread acceptance and became
      a standard of care in routine clinical practice by offering high-speed, non
      invasive, thin-slice diagnostic scanning for a wide range of clinical
      applications in radiology and cardiology. In the past year, the industry has
      witnessed an explosive increase in the amount of data obtained by MSCT and in the
      number at acquired slices to 32 and 64. While some experts have argued that a 16
      slice system is sufficient from a practical standpoint, a closer examination of
      32- and 64-slice systems offers new and superior clinical benefits over and above
      16-slice technology, especially in imaging of the coronary arteries and in
      multiphase and functional studies. With the introduction of 32-slice computed
      tomography (CT) systems, the routinely acquired slice thicknesses have been
      reduced to 0.5 mm and 1 mm. At these slice thickness levels, it is possible to
      acquire isotropic volume data sets in all CT scans. Recently, diagnosis based on
      isotropic volume data has become the standard in CT imaging as it offers far
      greater clinical benefits than previous 16-slice CT technology. While many of the
      clinical benefits of a 64-slice CT system center around imaging the heart, there
      are several distinct areas in the radiology practice that benefit as well. One
      key area is in the field of interventional neuroradiology and the ability to
      separate venous from arterial flow using computed tomography angiography (CTA).
      The evolution of MSCT has opened up new frontiers in diagnostic imaging that were
      unimaginable just a few years ago.

PMID- 15988874
TI  - Non-invasive technology used to detect and treat heart disease.

PMID- 15988875
TI  - Ease off the gas pedal.

PMID- 15988876
TI  - Hooked on electronics.

PMID- 15988877
TI  - In search of intelligent solutions.

PMID- 15988878
TI  - Lending climate brightens. Cautious optimism order of the day.

PMID- 15988879
TI  - Focus on caregiving. Falls prevention in dementia populations.

PMID- 15988880
TI  - New clinical materials and techniques in guided tissue regeneration.
AB  - AIM: To review the evidence on using Guided Tissue Regeneration (GTR) techniques
      and materials in various clinical circumstances. METHOD: Literature review. MAIN
      OUTCOME MEASURES: The success of GTR techniques and materials in halting or
      reversing the destruction of tooth attachment apparatus caused by progressive
      periodontal disease. RESULTS: GTR and osseous grafting are the two techniques
      with the most clinical and histological documentation of periodontal
      regeneration. CONCLUSIONS: GTR materials, whether non-resorbable or
      bioabsorbable, give similar clinical results. GTR procedures have been
      demonstrated to be clinically effective in treating infrabony osseous defects,
      recession defects, preserving alveolar bone in recent extraction sites and in
      some types of furcation defects. GTR procedures are technique sensitive and are
      adversely affected by poor home oral hygiene care, poor follow-up professional
      maintenance care and smoking.

PMID- 15988881
TI  - Setting global goals for oral health for the year 2010.
AB  - OBJECTIVE: To discuss the determinants for the possible setting of global goals
      for oral health for the year 2010. RESULTS AND CONCLUSIONS: If the application of
      oral health goals is to measure the outcome of oral health strategies and plans,
      they need to be substantially redesigned to reflect disparities in oral health
      and access to oral health care. It is no longer acceptable to focus only upon one
      or two arbitrarily selected disease entities and say these reflect the oral well
      being of communities and the success (or failure) of oral health programmes. The
      use of validated socio-dental indicators to assess prevalence of socio-dental
      impacts seems essential, as does the avoidance of goals for conditions that are
      strongly influenced by culture, class, ethnicity and other widely variable local
      influences.

PMID- 15988882
TI  - Oral health services in PR China as evaluated by dentists and patients.
AB  - OBJECTIVE: To describe the function of oral health services and the delivery of
      oral health care in PR China. DESIGN: Cross-sectional surveys. Self-administered
      questionnaires gathered information on professional practices and attitudes of
      Chinese dentists. Patients were examined clinically for caries and services
      rendered. Patients were interviewed about oral health status, reason of dental
      visits and consumption of services, perceived need for care and self-care
      practices. SETTING: Wuhan City of the Hubei Province of China. SUBJECTS: Random
      samples of dentists (n = 250) working with child and adult patients in 1998 in
      Wuhan City. Each dentist had a representative sample of 20 patients attending
      consecutively for care enrolled in the study. RESULTS: On average, the dentists
      saw 12 patients per day, with most time devoted to restorative treatment and
      extraction. The majority of dentists held the opinion that in China little
      attention is given to preventive care. Forty per cent of the patients were new to
      the dentists and more than half attended care because of pain or acute symptoms.
      The reported mean number of decayed, missing, and filled teeth varied from 2.6
      for 12-year-old patients to 10.7 for patients aged 65-74. Daily toothbrushing was
      practised by more than 90% of the patients in all age groups, however, the
      tradition of regular dental visits was weak. Most patients (51-75 per cent)
      attended for care due to acute problems or pain. CONCLUSION: The study indicated
      the need for reorientation of the Chinese oral health services towards
      prevention.

PMID- 15988883
TI  - Social images of medicine and dentistry in Japan. An exploratory study using
      correspondence analysis.
AB  - OBJECTIVE: To investigate social images associated with dentistry in comparison
      with nine other medical disciplines. DESIGN: A questionnaire survey among members
      of the general public. Subjects were asked to state, in not more than five words,
      the images which they associated with each of the ten disciplines. SETTING:
      Komaki City, Shikatsu Town and Nagoya City in Japan. PARTICIPANTS: 261
      respondents from a convenience sample of 300 residents, not associated with any
      branch of medicine. OUTCOME MEASURES: Frequency distribution of word images used
      on at least five occasions and a correspondence analysis of the responses for the
      ten disciplines. RESULTS: Of the 163 coded image items, 60 were related to
      internal medicine, 56 to dentistry, 55 to dermatology, 51 to orthopaedic surgery,
      51 to ophthalmology, 50 to surgery, 47 to obstetrics and gynaecology, 43 to
      otolaryngology, 40 to paediatrics and 33 to psychiatry. Correspondence analysis
      applied to the 163 items and 10 medical disciplines indicated that three similar
      paired image groups were found, namely between dermatology and ophthalmology,
      surgery and orthopaedic surgery, and between dentistry and internal medicine,
      which were the more commonly encountered disciplines across all age groups.
      However, compared with the other specialities, dentistry had a significantly
      greater association with pain, this response being four times more common than
      for surgery. CONCLUSIONS: This group of members of the public in Japan perceived
      dentistry-associated images in a similar way to internal medicine, but the
      negative associations with pain need to be addressed by the dental profession and
      health educators alike.

PMID- 15988884
TI  - Utilisation of dental care at the University Dental Hospital, Southern Thailand.
AB  - OBJECTIVES: To identify the need and demand for dental care among patients
      attending the government University Dental Hospital (Prince of Songkla
      University, PSU) located in Southern Thailand (Haad Yai, Songkhla). DESIGN: Data
      were analysed descriptively focusing particularly on demography, occupation,
      chief complaints, and treatment needs of patients. SUBJECTS: Records of 4,175
      self-referred and dental and medical practitioner referred patients, who
      registered for the first time at the University Dental Hospital in 1992. RESULTS:
      Patients in the 21-30, 11-20, 31-40 age groups showed the greatest demand for
      dental services (30.5 per cent, 26.4 per cent, 24.6 per cent respectively)
      especially females. Conservative dentistry, oral surgery, prosthodontics and
      orthodontics were the main types of dental treatment needed (43.8 per cent, 28.2
      per cent, 22.4 per cent, 3.6 per cent respectively). CONCLUSIONS: Eighty per cent
      of patients sought dental treatment because of symptoms. Age, sex, occupation,
      and distance were associated with the utilisation of dental services.

PMID- 15988885
TI  - Reasons for tooth extraction in a Brazilian population.
AB  - AIM: To identify the reasons for tooth extraction in Recife, Brazil and to test
      whether they differ by socio-economic groups and levels of caries experience.
      DESIGN: Cross-sectional survey. SETTING: Ten health centres of the public health
      system and ten health centres of insurance companies. PARTICIPANTS: Patients
      attending health centres. METHODS: Ten dentists from each selected centre and two
      patients from each selected dentist were randomly selected from; the list of all
      health centres in Recife, all dentists carrying out dental extractions at each
      selected centre and all patients who had an appointment with the selected
      dentists respectively. Participants were examined by both the researcher (AC) and
      dentists. OUTCOME MEASURE: Reasons for tooth extraction. RESULTS: Of the 404
      teeth extracted, 70.3 per cent were because of caries and its sequelae; 15.1 per
      cent because of periodontal disease; 6.4 per cent for pre-prosthetic reasons; 3.7
      per cent wisdom teeth, 2.5 per cent for orthodontic reasons and 1 per cent for
      trauma and patient's request. A trend was observed for patients with less than
      secondary school education and lower salaries to have more tooth extraction due
      to caries, but the differences were not of statistical significance.

PMID- 15988886
TI  - Endodontic patient profile of Hacettepe University, Faculty of Dentistry in
      Ankara, Turkey.
AB  - AIM: To assess previous patient experience of endodontic treatment and to
      quantify their satisfaction with the endodontic treatment provided in a dental
      school clinic. DESIGN: Self-completed questionnaire. SETTING: Hacettepe
      University, Faculty of Dentistry, Department of Endodontics, Ankara, Turkey.
      PARTICIPANTS: 200 randomly selected, scheduled non-emergency patients in good
      health and older than 11 years who were to be treated by undergraduate, graduate
      students and academics. MAIN OUTCOME MEASURES: Patient satisfaction and attitudes
      to root canal therapy. RESULTS: 96 per cent of patients, regardless their level
      of education, age and sex, reported that they expected RCT would save their
      teeth. 15 per cent of the patients were in favour of extraction versus RCT before
      the therapy, but this reduced to only 2.5 per cent post treatment. 82 per cent of
      patients reported that they were satisfied with their treatment and the clinic.
      CONCLUSIONS: Increasing public knowledge of and interest in endodontic treatment
      indicates that the need for an increase in teaching of the subject and associated
      resources will be required.

PMID- 15988887
TI  - The initial dental health status of British Army Gurkha recruits.
AB  - AIM: To describe the initial dental health status of British Army Gurkhas who
      were recruited in 1999 and to compare the present caries data with previous
      unpublished data from before 1970 and 1983. DESIGN AND SETTING: A clinical
      examination was conducted on the 228 Gurkhas, the entire UK intake for 1999,
      during their second week of military training. The focus of the examinations was
      on caries experience. A questionnaire was employed to collect demographic data as
      well as information on the recruits' reported dental behaviour and beliefs.
      RESULTS: 1999 recruits who reported a dental problem within the past year were
      significantly more likely to have visited a dentist before compared to those
      recruits who reported no dental problems. The frequency distributions of D3MFT
      for the 1983 and 1999 recruits were very similar. CONCLUSIONS: Gurkha men are at
      relatively low risk of dental caries and predicted treatment time suggests a
      relatively small use of resources would be needed to make this group dentally
      fit. These recruits are an extremely homogeneous group who remain discernible
      from the general Nepalese population.

PMID- 15988888
TI  - Treatment of dentinal hypersensitivity using a dentine bonding system.
AB  - AIMS AND OBJECTIVES: Many agents have been used in treatment of dentinal
      hypersensitivity in the past, but dentine bonding systems have recently been
      suggested as being effective. This study examined the effectiveness of a dentine
      bonding system in the treatment of dentinal hypersensitivity in dental practice
      conditions. METHODS: Dentists in two dental practices agreed to carry out the
      project. One practice was in the UK, the other in India. A total of 34 patients
      who were diagnosed to have dentinal hypersensitivity were treated using the
      dentine bonding system. Patients were requested to record their perception of
      their pain on a 100mm linear scale, pre-treatment, one day and one week post
      treatment. RESULTS: All patients experienced relief of pain, both 1 day and 1
      week after treatment. Profile plots of the patients' perceived pain scores for
      the two practices separately indicated that there was a general trend across both
      practices for these to fall quite sharply one day after treatment and then
      generally level out one week post-treatment. There was evidence indicating a
      possible difference in pain perception in the two communities from which the
      patients were drawn. CONCLUSION: The dentine bonding system evaluated was
      successful in reducing the pain of dentinal hypersensitivity, at least in the
      short term.

PMID- 15988889
TI  - The prevalence of caries and of tooth tissue loss in a group of children living
      in a social welfare institute in Jeddah, Saudi Arabia.
AB  - AIM: To measure the prevalence of caries, rampant caries and erosion in a group
      of 4-5-year-old children living in an institution in the city of Jeddah in the
      West Province of Saudi Arabia. DESIGN: Descriptive, cross sectional. SAMPLE AND
      METHODS: A total of 80 children (51 boys, 29 girls) living in the Institute were
      examined visually for caries using BASCD criteria. Erosion of palatal and buccal
      surfaces of maxillary incisors was scored: 0 (no erosion), 1 (erosion into
      enamel), 2 (erosion into dentine) and 3 (erosion involving the pulp). RESULTS:
      Twenty-four of the Children (30 per cent) had caries and two had rampant caries.
      Mean dmft was 0.95 (+/- 2.03) and mean dmfs was 3.2 (+/- 6.51). These values are
      lower than other estimates for children of this age in Saudi Arabia. Ten children
      (12.5 per cent) had erosion affecting buccal or palatal surfaces of their
      maxillary incisor teeth. In seven, erosion was confined to enamel but in three it
      extended into dentine. CONCLUSION: The lower caries levels seen in this group of
      children may be at least partly attributable to the effectiveness of strict
      dietary control and regular oral hygiene measures.

PMID- 15988890
TI  - 'Tis the time to say thank you and sayonara.

PMID- 15988891
TI  - Good fences.

PMID- 15988892
TI  - Report of the executive director - 2001.

PMID- 15988893
TI  - My friend, James Kahoe.

PMID- 15988894
TI  - The need for CE & your participation.

PMID- 15988895
TI  - Master craftsman & convention organizer.

PMID- 15988896
TI  - Information technology streamlines dental practice.

PMID- 15988897
TI  - The role of general anesthesia in pediatric dentistry.

PMID- 15988898
TI  - HDA volunteers doing a big job on the Big Island.

PMID- 15988899
TI  - Kalalau valley, nature at its best & most dangerous.

PMID- 15988900
TI  - Cultural discovery in Hiroshima.

PMID- 15988901
TI  - Sacred fillings.

PMID- 15988902
TI  - HDPAC: the Hawaii Dental PAC.

PMID- 15988903
TI  - Access to a brighter future.

PMID- 15988904
TI  - Passive fit: a technique for seating implant frameworks.

PMID- 15988905
TI  - Use of a thermoplastic retainer as an interim prosthesis for implant therapy: a
      case report.

PMID- 15988906
TI  - The dentist from Kathmandu.

PMID- 15988907
TI  - Seven habits of the Web-driven dentist: how to make the Web work for your
      business.

PMID- 15988908
TI  - Priming anticancer active specific immunotherapy with dendritic cells.
AB  - Dendritic cells (DCs) probably represent the most powerful naturally occurring
      immunological adjuvant for anticancer vaccines. However, the initial enthusiasm
      for DC-based vaccines is being tempered by clinical results not meeting
      expectations. The partial failure of current vaccine formulations is explained by
      the extraordinary complexity of the immune system, which makes the task of
      exploiting the potential of such a biotherapeutic approach highly challenging.
      Clinical findings obtained in humans so far indicate that the immune system can
      be actively polarized against malignant cells by means of DC-based active
      specific immunotherapy, and that in some cases this is associated with tumor
      regression. This implies that under some unique circumstances, the naturally
      'dormant' immune effectors can actually be employed as endogenous weapons against
      malignant cells. Only the thorough understanding of DC biology and tumor-host
      immune system interactions will allow researchers to reproduce, in a larger set
      of patients, the cellular/molecular conditions leading to an effective immune
      mediated eradication of cancer.

PMID- 15988909
TI  - Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies.
AB  - Cancer immunotherapy utilizing vaccines has relied upon the patients' pre
      existing immune activation capabilities, augmented by existing adjuvants, to
      promote tumor-antigen specific immune responses. Generating effective antitumor
      responses in this way requires overcoming multiple mechanisms of tumor evasion of
      the immune system. In addition, the generation of tumor immunity must overcome
      tolerance to tumor antigens, which in most cases are self-antigens. One approach
      to generate more effective immune responses to tumors is through the manipulation
      of co-stimulatory molecules that control T-cell reactivity through both positive
      and negative signaling mechanisms. This review will focus on the T-cell co
      stimulatory molecule CTLA4. Engagement of CTLA4 by the ligands B7-1 and B7-2
      imparts a negative signal to T-cells and results in alteration of T-cell activity
      and selection. In murine tumor models, antibodies to CTLA4 can promote tumor
      rejection and tumor immunity. Antibodies to human CTLA4 have entered clinical
      trials and demonstrated objective clinical responses, initially for metastatic
      melanoma. Interestingly, CTLA4 blockade has been associated with organ-specific
      inflammatory adverse events. These events usually respond readily to short-term
      anti-inflammatory treatment and cessation of drug treatment, and even when
      suppressed in this manner appear to correlate with clinically significant and
      durable antitumor responses.

PMID- 15988910
TI  - Therapeutic vaccines for prostate cancer: a review of clinical data.
AB  - Prostate cancer is the most common, non-cutaneous cancer and the second leading
      cause of cancer death among men in the US. A greater understanding of basic
      immunological principles has led to the development of a variety of new
      techniques, which in turn has led to advances in the field of prostate cancer
      vaccines. This review will discuss the rationale for the development of vaccines
      involving whole tumor cells and dendritic cells, as well as pox viral vectors,
      and will summarize selected clinical studies that have incorporated these
      strategies.

PMID- 15988911
TI  - Vaccine therapy for non-Hodgkin's lymphoma and other B-cell malignancies.
AB  - Immunity against tumor antigens, including the passive transfer of humoral
      (antibody-based) immunity or cellular immunity in the form of cytotoxic T
      lymphocyte clones, has been exploited for the treatment of non-Hodgkin's lymphoma
      and other B-cell malignancies in recent years. In many strategies, the idiotype
      expressed on B-cell malignancies is the antigen used to induce active immunity.
      Early studies using purified idiotype, immune adjuvant and cytokines to induce
      anti-idiotype immunity have demonstrated that these methods are safe and
      potentially effective, and they are now being tested in prospective, randomized
      clinical trials. Methods for improvement include recombinant sources of idiotype,
      DNA vectors, enhancement of antigen delivery and presentation by using dendritic
      cells, boosting immune help through the use of cytokine delivery or foreign
      antigens, and blocking negative regulators. The goal of this approach is to
      induce lasting and individualized immunity against B-cell malignancies that is
      readily available and cost-effective.

PMID- 15988912
TI  - Telomerase as a target for cancer therapy.
AB  - Normal human somatic cells undergo telomeric attrition and replicative senescence
      because of inadequate levels of telomerase; however, most immortal cancer cells
      cope with this by deregulating telomerase. Inhibiting telomerase causes renewed
      telomeric attrition and eventually highly specific death in cancer cells that
      express the enzyme. However, most cancer cells undergo many cell divisions before
      they die, opening the way for acquired drug resistance. Recent attempts to solve
      this problem include the development of drugs that are more potent catalytic
      inhibitors, that deny telomerase access to the telomere in situ, or affect
      telomere structure. Combinations of these approaches may ultimately produce the
      best clinical results.

PMID- 15988913
TI  - Activity of epothilones.
AB  - Epothilones represent a novel class of anticancer drugs which inhibit the cell
      cycle and strongly influence cell division. The biological activity of
      epothilones is associated with their capacity to bind to the protein tubulin of
      microtubules and to disturb the dynamic equilibrium between microtubule
      assembling and disassembling. Consequently, in dividing cells, it leads to
      mitotic arrest and to apoptotic cell death. A number of epothilones demonstrate a
      potent inhibitory effect on cell proliferation in human tumor cell lines, as well
      as antitumor activity in experimental animals bearing human tumor xenografts.
      This review will focus on the recent preclinical studies of the in vitro and in
      vivo activities of four epothilones, EPO-906, BMS-247550, KOS-862 and BMS-310705.
      Several epothilones are undergoing clinical evaluation and are promising
      candidates for advanced cancer therapy.

PMID- 15988914
TI  - ABT-751 (Abbott).

PMID- 15988915
TI  - Tasidotin HCl (Genzyme).

PMID- 15988916
TI  - CNTO-328 (Centocor).

PMID- 15988917
TI  - [Somnambulism: clinical and eletrophysiological aspects].
AB  - The authors review the literature on the epidemiology, the clinical and
      electrophysiological symptoms of somnambulism. The disorder specified as "nREM
      parasomnia with awakening disorder" belongs to the nREM sleep (awakening)
      parasomnias. In most of the cases its occurence is familial with the highest
      prevalence at age 12 year. Above age 12 year most cases recover whereas 6% of
      prevalence is reported in adults. It is probable that most patients seek medical
      help only in severe cases associated with injuries, accidents or violence. Its
      etiology is unknown; in essence it is a sleep regulation disorder characterised
      by a dissociated state of partial awakening from nREM sleep: the motor system
      becomes awake while consciousness remains clouded. There are several medicines
      inducing somnambulism in patients otherwise free from this disorder. In
      somnambule patients the most important provoking factors are sleep deprivation as
      well as pathological states and circumstances evoking sleep loss. Somnambulism
      should be differentiated from complex partial epileptic seizures and REM
      behaviour disorder. As there is no specific treatment at the moment it is
      important to assure safe sleeping circumstances - ground flour, closed windows,
      and no fragile furniture. Clonazepam and selective serotonin reuptake inhibitors
      prove sometimes effective, but the most effective methods in decreasing the
      frequency of somnambule episodes are the regular sleep-wakefulness schedule and
      the avoidance of sleep deprivation.

PMID- 15988918
TI  - [Carotid intima-media thickness measured by ultrasonography: effect of different
      pharmacotherapies on atherosclerosis progression].
AB  - The clinical manifestations of arteriosclerosis (cardiovascular, stroke and
      peripheral artery diseases) represent the leading causes of morbidity and
      mortality in industrialized countries. The early in vivo diagnosis and follow up
      of subclinical progression of arteriosclerosis is important for the evaluation of
      efficient preventive and therapeutic interventions. The carotid artery intima
      media thickness (IMT) is a reliable surrogate marker of the arteriosclerosis and
      could be easily investigated with high resolution B-mode sonography. Due to its
      good reproducibility, the IMT measurement is optimal for tracking the progression
      or regression of atherosclerotic disease. The increase of IMT is influenced by
      numerous vascular risk factors (age, smoking, hypertension, dyslipidemia, alcohol
      etc.) and positively associated with the incidence of vascular events in the
      arterial vasculature (stroke, myocardial infarct). Studies with lipid-lowering,
      antihypertensive, antidiabetic drugs, hormones confirmed, that modifying of
      vascular risk factors significantly reduces the progression of IMT. It is
      probable, that reduced progression of IMT is also accompanied with the decrease
      of future vascular events.

PMID- 15988919
TI  - [Possibilities in the treatment of primary biliary cirrhosis].
AB  - The primary biliary cirrhosis (PBC) is a chronic, progressive disease of unknown
      origin with immune pathomechanism. The disease is accompanied with the chronic
      inflammation of the small and middle intra-hepatic bile ducts. It occurs in 90
      per cent of women. The authors summarizes the possibilities ot its therapy after
      the review of the pathogenesis and clinical findings. They discuss the
      pathomechanism and the effects on the biochemical and histological findings of
      ursodeoxycholic acid (UDCA), which is the basis therapy of this disease, The
      place and indication of immunosuppressive drugs as well as possibilities of
      immune modulation are also reviewed on the basis of literary data. The therapy in
      the complication PBC and concomitant diseases are also discussed. The authors
      mention the opportunities of the therapy which will be applied in the future as a
      fruitful therapy.

PMID- 15988920
TI  - [Novel treatment modalities in cutaneous T cell lymphoma. Biologic response
      modifiers].
AB  - Biologic response modifiers. Biologic response modifiers such as IFN-alpha,
      retinoids and extracorporeal photopheresis have been widely used in the treatment
      of cutaneous lymphoma. The novel treatment modalities like cytokine therapies,
      monoclonal antibodies and fusion proteins have been used only in limited number
      of patients with therapy refractory diseases, in advanced stages. The treatment
      responses of novel cytokine therapies, IFN-gamma, IL-2 and IL-12, are
      encouraging. Anti- CD52 monoclonal antibody treatment resulted in complete or
      partial remission in both mycosis fungoides and Sezary syndrome, however serious
      infectious complications hinder the wide-range usage. DAB 389IL-2 fusion protein
      consisting of the toxic portion of diphtheria toxin and the IL-2 sequence has
      been used for advanced stages of CTCL. RXR retinoids are effective treatment for
      both early and advanced stages, in form of monotherapy or in combination
      treatment.

PMID- 15988921
TI  - [Primary squamous cell carcinoma of the breast].
AB  - Primary squamous cell carcinoma of the breast is a rare tumor that presents an
      unique biologic behavior. Thus, it challenges the justification for routine
      axillary dissection and adjuvant therapy. Squamous cell carcinoma has several
      unique biologic characteristics; it is associated with a lower rate of lymph node
      metastasis and significant rate of distant metastasis without lymph node
      involvement. The diagnosis of primary squamous cell carcinoma of the breast can
      only be established if the metastatic tumor origin can be excluded, the tumor is
      not attached to the skin and no other histological type of carcinoma is detected
      in the course of detailed histological examination. The authors present two cases
      from their own experience. One of them has preexisted fine needle aspiration
      cytology.

PMID- 15988922
TI  - Clinical follow-up of conjunctival malignant melanoma.
AB  - PURPOSE: To investigate the clinical features and course of conjunctival
      malignant melanoma in Korea. METHODS: The medical records of 15 patients, 5 males
      and 10 females, diagnosed with conjunctival malignant melanoma who had been
      treated at Severance Hospital from May 1991 to March 2004 were reviewed
      retrospectively. The clinical parameters of the patients, tumors, and treatment
      were analyzed for their relation to outcome measures. RESULTS: The mean age at
      the time of diagnosis was 53.4 years (+/- 11.7 years). In all cases, the disease
      was unilateral and all patients had experienced at least one recurrence. Local
      lymph node metastasis was found in 3 patients (20%) and the mean time to
      metastasis was 3.5 years. Systemic metastasis was found in 6 patients (40%) and
      the mean time to metastasis was 9.3 years. There were 5 cases of tumor-related
      death (33.3%), 4 of which were attributed to systemic metastasis. The Kaplan
      Meier estimates of cumulative survival rate were 90% at 30 months and 56.6% at 70
      months. CONCLUSIONS: Although conjunctival malignant melanoma is a rare disease,
      it is life-threatening and complete tumor excision at an early stage is
      mandatory, as is additional therapy to prevent local recurrence and systemic
      metastasis.

PMID- 15988923
TI  - Impression cytology of herpetic simplex keratitis in rabbits.
AB  - PURPOSE: To use impression cytology to examine the structural changes in corneal
      epithelial cells infected with the herpes simplex virus in rabbit eyes. METHODS:
      Corneal surfaces of 7 rabbits were scratched using a 25-gauge needle. Herpes
      simplex virus (type 1, Kos strain) was inoculated to the injured cornea. As the
      corneal diseases were observed using slit lamp biomicroscopy, impression cytology
      was performed for 18 days after inoculation. Specimens were stained with
      hematoxylin-eosin and examined using optical microscopy. RESULTS: Corneal lesions
      consisted mainly of round epithelial cells, inflammatory cells, ballooning cells,
      multinucleated giant cells, and various inclusion bodies. Over time, the comeal
      epithelial cells peeled away as a result of corneal edema in the comeal lesions.
      Dendritic lesions were also observed. In the recovery phase, the number of
      detached cells and infiltrated inflammatory cells decreased. CONCLUSIONS: It was
      presumed that dendritic lesions might have been formed at the scratched cornea
      region, thereby aggravating the epithelial cells falling off as a result of the
      infiltration of inflammatory cells. These cytopathologic effects occur in
      experimental herpes simplex keratitis.

PMID- 15988924
TI  - Effect of experimental scleral shortening on axial length of the rabbit eye.
AB  - PURPOSE: To evaluate the change of axial length (AL), intraocular pressure (IOP),
      and corneal astigmatism after scleral shortening with scleral invagination in the
      rabbit eye. METHODS: The authors performed scleral shortening (3 mm) with scleral
      invagination in two groups of 6 eyes each: 180 degrees (group 1) and 360 degrees
      (group 2). RESULTS: Average AL shortening was more prominent in group 2 (0.5 +/-
      0.17 mm) than in group 1 (0.37 +/- 0.29 mm), but the difference was not
      statistically significant. IOP increased immediately after the procedure and was
      maintained at a high level through 2 months postoperatively. Induced corneal
      astigmatism was more prominent in group 1 than in group 2. The difference was
      statistically significant in group 1 (p<0.05) but not in group 2. CONCLUSIONS: In
      the scleral shortening with scleral invagination procedure, a large amount of
      scleral invagination resulted in more shortening of axial length, but there was
      more corneal astigmatism in 180-degree invagination of the sclera than in 360
      degree. Further research is required to determine the effect of the extent of
      scleral invagination on the change of these values.

PMID- 15988925
TI  - Study of blue and red flash in dark-adapted electroretinogram.
AB  - PURPOSE: To investigate the characteristics of the waveform generated by blue and
      red light stimulations in a dark-adapted electroretinogram (ERG) and those of
      cone responses in the dark-adapted condition. METHODS: The study subjects were 52
      persons (88 eyes) with no previous medical history. The author recorded b-waves
      (rod response) with red light stimulation and the x-waves (dark-adapted cone
      response) that appeared before the b-waves. The author also recorded b-waves with
      blue light stimulation, which had the same amplitude as the b-waves from the red
      light stimulation. The differences with respect to age and gender were studied.
      Waveforms of the dark-adapted cone ERGs were recorded by using a digital
      subtraction technique. RESULTS: The x-wave always appeared before the b-wave with
      0 dB (2.4 cd.s/m2) red stimulation. With blue stimulation, a b-wave equivalent to
      the b-wave stimulated with the red light of 0 dB intensity appeared at an average
      of -14.57 dB. The implicit time for the b-wave was delayed significantly for the
      male group. There were no significant differences between different age groups.
      The dark-adapted cone ERG demonstrated the waveform of a negative response
      followed by a series of oscillatory potentials (OPs) and a positive response.
      CONCLUSIONS: The cone responses were followed by the rod responses with red light
      stimulation of 0 dB in the dark-adapted ERG. The waveforms of the cone ERGs were
      obtained in dark adaptation with red and blue light stimulation.

PMID- 15988926
TI  - Bilateral retinal dysplasia and secondary glaucoma associated with homozygous
      protein C deficiency.
AB  - PURPOSE: Protein C deficiency is an autosomal recessive disorder, which
      predisposes the patient to potentially blinding and widespread lethal
      thromboembolic complications, especially in the homozygous type. We here report
      the first Korean case of ophthalmic involvement and its surgical treatment in
      homozygous protein C deficiency. METHODS: A 3.4kg, full term girl was born by
      normal delivery but showed bilateral leukocoria on day 2. Laboratory results
      disclosed a very low protein C activity level (10%) in the patient and moderately
      decreased levels in the other family members. Ophthalmic examination showed
      bilateral corneal opacity and shallow anterior chamber. B-scan ultrasonography
      which showed intravitreal mass lesions without microphthalmos and a funnel-shaped
      retinal detachment suggested bilateral retinal dysplasia. RESULTS: As the eyes
      were under progression of secondary glaucoma, bilateral lensectomies were
      performed at 2 months old and corneal opacity was regressed to some degree.
      However, at 14 months old, the left eye showed moderate corneal opacity with a
      band keratopathy. CONCLUSIONS: Although visual outcome was very poor after
      surgery, we could impede or slow down the progression of secondary glaucoma and
      save the eyeballs in the infant with homozygous protein C deficiency.

PMID- 15988927
TI  - Protective effect of heat shock proteins 70.1 and 70.3 on retinal photic injury
      after systemic hyperthermia.
AB  - PURPOSE: This study aimed to determine the relationship between the heat shock
      protein 70 from hsps70.1 and 70.3 on retinal photic injury after systemic
      hyperthermia. METHODS: Eight-week-old female C57BU6 mice were kept at a constant
      temperature of 41-42 degrees C for 25-30 minutes. After dark-adaptation for 8
      hours, intense light of 11000 lux was maintained for 6 hours. Histology and
      immunohistochemistry for the inducible heat shock protein 70 (hsp70), the
      constitutive heat shock protein 70 (hsc70), and westem blot analysis, reverse
      transcriptase-polymerase chain reaction for hsp70.1 and hsp70.3 were performed
      just before photic injury and after 1, 4, 7, and 14 days. RESULTS: Light-induced
      retinal degeneration was prevented by thermotolerance. After hyperthermia, hsp70
      was densely expressed in the inner segment of the photoreceptor layer on the
      photic injury. Hsp70 expression increased for 4 days after photic injury and
      slowly decreased thereafter. mRNA from hsp70.3 was induced earlier than that of
      hsp70.1. CONCLUSIONS: Retinal photic injury was prevented by hyperthermia-induced
      hsp70. Hsp70 from hsp70.3 may be a rapid and short-lived responder, and that from
      hsp70.1 is a slower and more sustained responder. Hsp70 from hsp70.3 may be an
      initial retinal chaperone while hsp70 from hsp70.1 may be a sustained chaperone.

PMID- 15988928
TI  - Intraocular pressure elevation after intravitreal triamcinolone acetonide
      injection.
AB  - PURPOSE: This study investigated firstly the change of intraocular pressure (IOP)
      after injection of intravitreal triamcinolone acetonide (IVTA) for the treatment
      of macular edema and secondly the factors that influence these changes. METHODS:
      A prospective, non-comparative study was performed in 60 patients at Kangnam
      Sacred Heart Hospital from October 2003 to September 2004. All the patients
      received 4-mg IVTA injection. RESULTS: Mean IOP was elevated from the day after
      injection and peaked at 20.5 mmHg after 2 months (p=0.000). Twenty-six eyes
      (43.3%) showed significant IOP elevation. IOP was not controlled despite full
      glaucoma medication in 7 (11.7%) eyes. Two eyes underwent filtering surgery.
      Younger age was a statistically significant predictive factor for IOP elevation
      (p=0.009). CONCLUSIONS: In this study, patients who needed filtering surgery
      developed an IOP spike within one week after the injection. Therefore, clinicians
      should consider checking IOP at the end of the first week. Furthermore, greater
      cautions is mandatory with relatively younger patients.

PMID- 15988929
TI  - Decompression retinopathy after trabeculectomy.
AB  - PURPOSE: To present a case of a unilateral diffuse retinal hemorrhage in a 15
      year-old girl, who underwent bilateral trabeculectomy for steroid induced
      glaucoma. METHODS: Despite the maximally tolerable medical treatment, IOP in the
      right eye remained above 50 mmHg for four months, and was simultaneously elevated
      in the left eye. So we performed bilateral trabeculectomy. RESULTS: On the first
      postoperative day, diffuse retinal hemorrhages were observed in the right eye;
      however, no retinal hemorrhage was found in the left eye. The hemorrhages
      resolved completely without consequences two months later. CONCLUSIONS: In the
      case of high IOP for a long period, sudden lowering of IOP may acutely increase
      the blood flow and consequently rupture multiple retinal capillaries because of
      altered autoregulatory function. Special care is therefore needed to prevent an
      abrupt fall in IOP before, during, and after surgery, especially when IOP has
      been highly elevated for an extended period.

PMID- 15988930
TI  - The clinical features of Korean patients with Duane's retraction syndrome.
AB  - PURPOSE: To describe the clinical features of Duane's retraction syndrome (DRS)
      in Korean patients. METHODS: We retrospectively analyzed the 78 DRS cases that
      presented to our department between 1995 and 2004. The clinical features
      investigated included sex distribution, laterality, type of presentation,
      deviation in primary position, anomalous vertical movements, face turn, amblyopia
      and anisometropia. RESULTS: There were 38 (48.7%) affected males and 40 (51.3%)
      females. Left eye predominance (83.3%) was observed, as was type I presentation
      (85.9%). Orthotropia was found to be the most common primary position in 46 cases
      (59.0%). Face turn in unilateral DRS was noted in 13 patients (17.1%). There were
      6 cases (7.7%) with anisometropia and 4 (5.1%) with amblyopia. CONCLUSIONS: The
      clinical manifestations of DRS in our study were different from those of
      equivalent Caucasian studies yet similar to those previously reported for Asian
      groups. Racial and regional differences were noted, for which further research is
      needed to elaborate the reasons and mechanisms.

PMID- 15988931
TI  - Change of stereoacuity with aging in normal eyes.
AB  - PURPOSE: Stereopsis in normal subjects aged between 7 and 76 years was compared
      to examine changes in stereopsis with age. METHODS: Eighty subjects with no
      ocular disease were divided into 8 groups by age. Near stereopsis was evaluated
      with the TNO, Titmus, and Randot tests; distance stereopsis with the Mentor B-VAT
      II video acuity tester. RESULTS: The results of all 4 tests showed decreased
      stereopsis with increasing age (p<0.05). Compared to the stereoacuity of 7 to 10
      year-old group, both the TNO and distance stereopsis test results were
      significantly decreased for the 6th, 7th, and 8th decade groups, while both the
      Titmus and Randot test results were significantly decreased for the 8th decade
      group (p<0.05). CONCLUSIONS: Overall, both near and distance stereopsis decreased
      with increasing age. Thus, decreased stereopsis should be taken into account when
      performing the stereopsis test.

PMID- 15988932
TI  - The clinical course of recurrent exotropia after reoperation for exodeviation.
AB  - PURPOSE: To determine the clinical course of recurrent exotropia after a
      secondary operation for exotropia. METHODS: The surgical results in 58 patients
      who had undergone reoperation for recurrent exotropia (reoperation group) were
      retrospectively investigated and compared with those of 100 patients who had
      undergone primary strabismus surgery only (primary operation group) using
      survival analysis. RESULTS: In the reoperation group, recurrence occurred in 19
      of the 58 patients (33%). Survival analysis revealed that the recurrence rates in
      the reoperation group were significantly lower than those in the primary
      operation group at the same follow-up period after the corresponding strabismus
      surgery (p=0.018). The distant esodeviation at the postoperative 1st week after
      reoperation was the only significant factor associated with the recurrence after
      reoperation (p=0.01). CONCLUSIONS: Exotropia did recur after a secondary
      operation, although the recurrence rate was lower than that after a primary
      operation only.

PMID- 15988933
TI  - Shift of colorimetric values in ishihara pseudoisochromatic plates with plate
      aging.
AB  - PURPOSE: This study aimed to quantify the shift of colorimetric values in the
      Ishihara pseudoisochromatic test with aging of the plates. METHODS: Three sets of
      Ishihara pseudoisochromatic plates with different published dates (printed in
      1971, 1983 and 2001) were tested. Positions matching 32 dots with 13 colors were
      chosen from each set and the colorimetric values with the CIELAB and HSB/HLS
      color systems were measured with a spectrophotometer. Lightness (L*), red-green
      (a*), blue-yellow (b*), chroma, red hue, yellow hue, and green hue values from
      each set were compared. RESULTS: L* and chroma values were significantly higher
      in the older versions. The a* values shifted to red (increased a*) and the b*
      values shifted to yellow (increased b*) with plate aging. CONCLUSIONS: Our
      results showed that the pseudoisochromatic plates had significant changes in
      color values and a directional shift with aging.

PMID- 15988934
TI  - Development of pupillography using image processing.
AB  - PURPOSE: Pupillary examination is an important objective method to diagnose
      lesions of the anterior visual pathways. However, errors and faults may easily
      alter the interpretation and value of the test as it is highly dependent on the
      examiner's skills. Therefore, we tried to develop a pupillography which is
      independent of the examiner. METHODS: Hardware composed of a binocularly
      measuring instrument adapted for an infrared charge coupled device (CCD) was
      developed. Two arrays of infrared light emitting diodes (LED) were supplied in
      front of each of the subject's eyes. A microcontroller to modulate these LED was
      developed, as was software to save and analyze the pupil images. The hardware was
      able to deliver a light to either eye or to both eyes, and to change the time,
      frequency, and intensity of the stimulus. The software automatically analyzed the
      pupil size and location by image processing. Pupil size was calculated
      continuously. After artifact elimination, the response amplitudes of the pupils
      were determined for the right and left pupils. RESULTS: Pupillary images of size
      320 x 240, at 30 frames/second, were saved and processed to evaluate the change
      of the actual pupil size and the velocity of pupillary response. CONCLUSIONS: A
      pupillography to measure, save and analyze the pupillary response using image
      processing was developed. Further detailed clinical studies with a large number
      of patients will be required to validate this new method.

PMID- 15988935
TI  - A Korean case of Cornelia de Lange syndrome.
AB  - PURPOSE: Cornelia de Lange syndrome is a rare disease showing characteristic
      facial appearance, developmental delay, growth retardation, low birth weight,
      skeletal formation anomaly, hirsutism and various ophthalmologic problems.
      METHODS: We experienced a case of an 18-year-old female with Cornelia de Lange
      syndrome showing superficial keratitis with entropion, ptosis, high myopia,
      lacrimal cutaneous fistula and characteristic facial appearance. She was born
      with low birth weight, operated for cleft palate and diagnosed with ventricular
      septal defect. In addition, she showed psychological lag and developmental
      impairment. RESULTS: We performed entropion correction surgery, administered
      medical therapy for superficial keratitis and prescribed glasses for her myopia.
      CONCLUSIONS: This is the first case report on the successful correction of
      entropion with Cornelia de Lange syndrome in Korea.

PMID- 15988936
TI  - A case of congenital corneal keloid.
AB  - PURPOSE: To describe a case of unilateral comeal keloid and present the clinical
      and histopathological findings and the management. METHODS: A 23-year-old Asian
      male patient was examined for a white spot on the left cornea that had been
      present since birth. On biomicroscopic examination, a well-demarcated
      vascularized comeal mass was found located nasal to the center. The pupil was
      displaced superiorly, and gonioscopic examination showed peripheral iridocomeal
      adhesion at 12 o'clock. The patient underwent penetrating keratoplasty. RESULTS:
      Histopathologic study showed a variously thickened epithelial layer, an absence
      of Bowman's layer, subepithelial fibrovascular hyperplasia, and an absence of
      dermal elements. These histopathologic findings suggested a congenital comeal
      keloid. The central graft comea remained clear at 18 months after surgery and the
      patient was satisfied with the result. CONCLUSIONS: Penetrating keratoplasty may
      be an effective surgical option for congenital keloids in young adult patients.

PMID- 15988937
TI  - Is the 'waste hierarchy' sustainable?

PMID- 15988938
TI  - What is waste? To whom?--An anthropological perspective on garbage.
AB  - What is waste? To whom?--An anthropological perspective on garbage explores the
      fact that what constitutes waste is a highly subjective notion. In Tacna, Peru,
      the place from where this article draws its empirical material, waste is not only
      seen as a risk to public health and the environment. Some find it is a mere
      aesthetic inconvenience, for others it is the only source of income. Yet another
      way of perceiving waste is as a social contagion, in which the negative qualities
      of garbage are transmitted to surrounding people in the eyes of others. Such
      perceptions of waste, it is argued, are important parts of local waste management
      systems, and the understanding of such perceptions might increase the
      effectiveness of waste management campaigns.

PMID- 15988939
TI  - Solid waste management techniques for the waste generated and brought down from
      campsites in the hill spots, trails and expedition tops.
AB  - The increasing self-generated solid waste from the visitors in the hill towns,
      trails and expedition tops is one of the most adverse forms of human impacts in
      mountain environments. The direct managing authorities, such as municipalities in
      the hill spots, have no proper places to dispose of municipal waste nor the other
      infrastructure required nor adequate funds. The trekking and expedition areas are
      entirely dependent on the moral responsibilities of the local people, as well as
      visitors, because these locations are in remote areas, outside municipal
      boundaries. Based on five major case studies representing the Himalayas, the
      status of solid waste generation, its physical composition and management options
      in tourist [Kullu: 1,219 metres above average sea level (m), Rewalsar: 1,300 m,
      Manali: 2,050 m], trekking (in and around the Valley of Flowers: 1,830-4,330 m)
      and expedition areas (Pindari valley: 2,300-5,500 m) were studied. The inflow of
      visitors ranged from 150,000 to 1,140,251 in the hill spots, and from 25,000 to
      116,392 in the expedition and trekking areas, respectively. The capita = t day 1
      waste generation varied from 200-300 g in hill spots and from 200-288 g in
      expedition and trekking areas, respectively. Biodegradable waste varied from 65.2
      to 83.1% of the total waste generated and was of greater quantity than non
      biodegradable waste in expedition areas. Non-biodegradable waste was the
      predominant form in the expedition (66.4%) and trekking areas (84.5%). The
      ultimate aim of the study is to make the concerned local people, visitors and
      government aware of the need to harness energy from waste. This can be done in
      various ways including biocomposting, and the reuse and recycling of waste
      otherwise considered valueless and useless.

PMID- 15988940
TI  - Moisture retention of municipal solid waste mixed with sewage sludge and ash in a
      semi-arid climate.
AB  - Mechanisms involved in moisture storage in refuse are explored using data from
      four sets of experiments in a semi-arid climate. Two laboratory series of
      experiments contained municipal solid waste (MSW) amended with sewage sludge, one
      with higher proportions of ash in the MSW than the other. Outdoor experiments
      contained waste streams with different proportions of ash. Field cells compared
      moisture retention of refuse and MSW co-disposed with sewage sludge. Sewage
      sludge at high loads was found to increase the moisture storage relative to
      unamended MSW. Belt-pressed sludge retained water as bound water that was
      released by decay and changing pH. Sun-dried sludge also retained more moisture
      than MSW alone. In gravimetric terms, ash reduced the storage potential of MSW,
      in laboratory and outdoor experiments. However, outdoor experiments released less
      leachate from ash-rich refuse than middle-income waste with no ash fraction.

PMID- 15988941
TI  - Leaching behaviour of elements and evaluation of pre-treatment methods for
      municipal solid waste incinerator residues in column leaching tests.
AB  - Two new pre-treatment methods (water-washing/carbonation and
      carbonation/phosphate stabilization) of municipal solid waste (MSW) incinerator
      residues were evaluated by column leaching tests under aerobic conditions and
      anaerobic conditions (which were changed to aerobic conditions after 10 months).
      A mixture of bottom ash and fly ash (5:1 ratio) was pre-treated using each
      method. Shredded incombustible residues (SIR) were added to each ash preparation
      in proportions similar to the ratios present in landfills. For comparison,
      landfill wastes typical of Japan, namely, a mixture of bottom ash, chelating-pre
      treated fly ash, and SIR, were also examined. Leachate samples were collected
      periodically and analysed over a 15-month period. When compared with chelating
      pretreatment, both water-washing/carbonation and carbonation/ phosphate
      stabilization reduced the leaching of Pb, Al, and Cu by about one to two orders
      of magnitude. Moreover, the initial concentrations of Ca and Pb in leachates from
      column of water-washing/carbonation were 56-57% and 84-96% less than those from
      the column of carbonation/phosphate stabilization. Therefore, water
      washing/carbonation was considered to be a promising approach to obtain early
      waste stabilization and to reduce the release of heavy metals to near-negligible
      levels. The leaching behaviour of elements was also discussed.

PMID- 15988942
TI  - Analysis of leachate pollution index and formulation of sub-leachate pollution
      indices.
AB  - An index known as leachate pollution index (LPI) for quantifying the leachate
      contamination potential of municipal landfills had been developed and reported by
      the authors. It is a quantitative tool by which the leachate pollution data of
      landfill sites can be reported uniformly. LPI is an increasing scale index and
      has been formulated based on the Delphi technique. It provides a convenient means
      of summarizing complex leachate pollution data and facilitates its communication
      to the general public, field professionals and policy makers. However, it is
      observed that the LPI, like any other environmental index, fails to effectively
      communicate the details about the strength of various pollutants/pollutant groups
      present. In an effort to make the LPI more informative and useful, it is proposed
      to divide the LPI into three sub-indices. The aggregation of these three sub-LPIs
      will result in the overall LPI. The formulation and the application of LPI and
      its three sub-indices are presented in this paper. It has been concluded that the
      splitting of LPI into three sub-indices provides a better insight on the strength
      of various pollutants and can be useful to the experts in deciding various
      management issues regarding leachate treatment. The leachate characteristics of a
      UK landfill have been used as a case study to demonstrate the calculation of
      three sub-LPIs and the overall LPI.

PMID- 15988943
TI  - Effects of equipment loadings on geosynthetic-lined slope behaviour.
AB  - When combined in the lining and covering of waste-containment facilities, soil
      and geosynthetic components protect the environment by acting as a hydraulic
      barrier. Equipment loading may significantly increase the tensile stress induced
      in geosynthetic components, leading to a potential stability problem. Large
      equipment loadings may also result in a localized circular slip surface during
      construction operations. New analytical method based on discrete element
      modelling is proposed for estimating the distribution of tensile force developed
      in the individual geosynthetic components of the lining system and for evaluating
      the safety factor of slope failure due to equipment loading. The analytical
      results of an example are presented to demonstrate the applicability of the
      analytical method for the lining system of a waste landfill. The analyses of the
      example show that equipment loading provide a substantial increase in the tensile
      forces of the geosynthetic components of a lining system and that the possibility
      of shallow failure due to equipment loading increases as the slope becomes
      steeper. This method is a useful tool for analysing the lining system of waste
      landfills with complex lining components.

PMID- 15988944
TI  - The use of volcanic soil as mineral landfill liner--I. Physicochemical
      characterization and comparison with zeolites.
AB  - The main physicochemical characteristics of the volcanic soil of Southern Chile,
      with allophane as the main pedogenic mineral phase were analysed and compared
      with common zeolites (clinoptilolite) of the European market. The ultimate goal
      of this study was to test volcanic soil for the use as mineral landfill liner.
      The main results indicated that the clay and silt fractions together of the
      volcanic soil were between 38 and 54%. The buffering capacity of the volcanic
      soil was higher compared with the studied zeolites, whereas the cationic exchange
      capacity of the volcanic soil (between 5.2 and 6.5 cmol + kg(-1)) is of the same
      order of magnitude of the studied zeolites (between 9.7 and 11.4 cmol + kg(-1)).
      Moreover, the anionic exchange capacity of the volcanic soil was higher compared
      to the zeolites analysed. The hydraulic conductivity of the volcanic soil,
      measured in the laboratory at maximum proctor density, ranges between 5.16 x 10(
      9) and 6.48 x 10(-9) m s(-1), a range that is comparable to the value of 4.51 x
      10(-9) m s(-1) of the studied zeolite. The Proctor densities of the volcanic soil
      are in a lower range (between 1.11 and 1.15 g ml(-1)) compared with zeolites
      (between 1.19 and 1.34 g ml(-1)). The volcanic soil physicochemical
      characteristics are comparable to all the requirements established in the
      Austrian landfill directive (DVO, 2000). Therefore, the use as mineral landfill
      basal sealing of the analysed volcanic soil appears reasonable, having a
      pollutant adsorption capacity comparable to zeolites. It is of special interest
      for Southern Chile, because there are no alternative mineral raw materials for
      basal liners of landfills.

PMID- 15988945
TI  - The use of volcanic soil as mineral landfill liner--III. Heavy metals retention
      capacity.
AB  - The volcanic soil of Southern Chile was tested for its heavy metal retention
      capacity. The maximum uptakes for CrO4(2-) (CrVI), Cu(2+), Zn(2+) and Pb(2+) were
      determined to be 2.74, 5.32, 5.86 and 7.44 mg g(-1), respectively. At a slightly
      alkaline pH value (7.5), it seems that a precipitation-adsorption process was
      responsible for the Cu(2+) and Zn(2+) uptake onto volcanic soil. All the
      determined values are of the same order of magnitude as natural zeolites heavy
      metals adsorption capacities. In addition, the heavy metals diffusion model
      through a 1 m volcanic soil mineral liner shows breakthrough times of 21.6, 10.2
      and 8.9 years, for Pb(2+), Zn(2+) and Cu(2+), respectively, confirming the trend
      obtained in the adsorption isotherms. The natural volcanic soil of Southern Chile
      is an interesting material for possible use as landfill mineral basal sealing. It
      has an appropriate sealing potential (average Kf value of 5.85 x 10(-9) m s(-1))
      and a heavy metals retention capacity comparable with natural zeolites. About two
      thirds of the agricultural land in Chile (approximately 0.4 million km2) is
      derived from volcanic ash, suggesting an important soil volume for future
      landfill projects, that could be obtained in sufficient quantities from urban
      building activities.

PMID- 15988946
TI  - A side-by-side comparison of two systems of sequencing coupled reactors for
      anaerobic digestion of the organic fraction of municipal solid waste.
AB  - The objective of this work was to compare the performance of two laboratory
      scale, mesophilic systems aiming at the anaerobic digestion of the organic
      fraction of municipal solid wastes (OFMSW). The first system consisted of two
      coupled reactors packed with OFMSW (PBR1.1-PBR1.2) and the second system
      consisted of an upflow anaerobic sludge bed reactor (UASB) coupled to a packed
      reactor (UASB2.1-PBR2.2). For the start-up phase, both reactors PBR 1.1 and the
      UASB 2.1 (also called leading reactors) were inoculated with a mixture of non
      anaerobic inocula and worked with leachate and effluent full recirculation,
      respectively. Once a full methanogenic regime was achieved in the leading
      reactors, their effluents were fed to the fresh-packed reactors PBR1.2 and
      PBR2.2, respectively. The leading PBR 1.1 reached its full methanogenic regime
      after 118 days (Tm, time to achieve methanogenesis) whereas the other leading
      UASB 2.1 reactor reached its full methanogenesis regime after only 34 days. After
      coupling the leading reactors to the corresponding packed reactors, it was found
      that both coupled anaerobic systems showed similar performances regarding the
      degradation of the OFMSW. Removal efficiencies of volatile solids and cellulose
      and the methane pseudo-yield were 85.95%, 80.88% and 0.109 NL CH4 g(-1) VS(fed)
      in the PBR-PBR system; and 88.75%, 82.61% and 0.115 NL CH4 g(-1) VS(fed0 in the
      UASB-PBR system [NL, normalized litre (273 degrees K, 1 ata basis)]. Yet, the
      second system UASB-PBR system showed a faster overall start-up.

PMID- 15988947
TI  - Quality is in the eye of the consumer.

PMID- 15988948
TI  - Health web site accreditation: opportunities and challenges.
AB  - The development of the health Internet creates opportunities and challenges for
      health care organizations. One challenge is building trust among users of online
      health resources. Research suggests that consumers do not fully trust health Web
      sites, with privacy and content quality among their concerns. Accreditation may
      offer a mechanism for health Web sites to demonstrate quality and trustworthiness
      to patients. URAC has created such an accreditation program, which was fully
      implemented in December 2001.

PMID- 15988949
TI  - Information therapy answers the Institute of Medicine's harsh report.
AB  - Information therapy is the prescription of specific information to a specific
      person at a specific time to help with a health decision. Correctly prescribed,
      information becomes medicine--powerful medicine. Information therapy can be as
      important to a patient's health as any drug, medical test, or surgery. Physicians
      value the information and advice they give to patients as their most important
      service, yet the way they perform that service hasn't changed for a hundred
      years. Doctors still rely chiefly on their clinical experience, their memory, and
      the spoken word to convey essential information to patients. When patients
      misunderstand, ignore, or forget the information, this vital service is wasted.

PMID- 15988950
TI  - Patients, physicians, and the Internet.
AB  - Washington-based Group Health Cooperative has been providing personalized
      services to patients over the Internet for a year through the MyGroupHealth
      member portal. We continue to refine our communications to meet the needs of our
      patients online in the absence of experience comparable to that which we have
      gained in 54 years of in-person and telephone interactions.

PMID- 15988951
TI  - Towers Perrin 2002 Health Care Cost Survey: what consumers and employers are
      doing about the increases.

PMID- 15988952
TI  - Public opinion, market share and the future of HMOs: a conversation with Allan
      Baumgarten.

PMID- 15988953
TI  - Patient care cancer clinical trials at the National Cancer Institute: a resource
      for payers and providers.
AB  - Clinical trials form the evidence base for medical decision making and may
      provide patients with life-threatening conditions their best chance to find an
      effective treatment. A growing number of states and the federal government are
      mandating coverage of the routine costs of cancer clinical trials, although the
      extent of coverage varies. Individual health plans are following suit on behalf
      of their beneficiaries. Trials conducted at the National Cancer Institute (NCI)
      are an attractive resource for payers, because NCI provides medical services at
      no charge, enables patient access to promising care, emphasizes continuity with
      patients' regular physicians, and makes the referral and enrollment process easy
      and efficient through its Clinical Studies Support Center's toll-free information
      line 1-888-NCI-1937.

PMID- 15988954
TI  - Stark II Final Rule (Phase I): some answers, more questions.

PMID- 15988955
TI  - Take the high road: build trust on the health Internet.

PMID- 15988956
TI  - Health information on the web.

PMID- 15988957
TI  - Boon for consumers? Hospital quality regulator and big business health purchasing
      coop join forces.

PMID- 15988958
TI  - Think before reacting to the lures of consumerism.

PMID- 15988959
TI  - Pharmaceutical company-sponsored disease management programs.

PMID- 15988960
TI  - Helen Primrose LeVesconte: occupational therapy clinician, educator, and maker of
      history.
AB  - BACKGROUND: The Canadian history of our profession is not well known and our
      identity is thought to suffer as a result. Helen Primrose LeVesconte (7896-1982)
      is one pioneer in our development whose story has not been told. PURPOSE: Our
      purpose is to explore LeVesconte's life and work in order to expand knowledge of
      our roots and thereby strengthen our identity. METHOD: Using interpretive
      biography methods we draw on LeVesconte's own writings, articles written about
      her, and archival documents to describe turning point moments in her life and to
      display meaningful patterns in her work. RESULTS: LeVesconte's work as a
      clinician and her role and reputation as an educator, show her to have been a
      strong and visionary leader. Her views on the client's role, the importance of
      the therapist-client relationship, prevention, community-based programs, and
      vocational rehabilitation are of particular interest. PRACTICE IMPLICATIONS:
      Because LeVesconte educated over 1,850 students while director of the
      occupational therapy program at the University of Toronto, her influence has been
      felt throughout the country. Her perspective is compared to current practice; and
      questions are raised as to aspects of her legacy and philosophy that might now be
      reconsidered.

PMID- 15988961
TI  - Perceptions of power mobility use and safety within residential facilities.
AB  - BACKGROUND: Power wheelchairs enhance quality of life by enabling occupation,
      improving self-esteem and facilitating social interaction. Despite these
      benefits, the risks associated with power mobility use raise serious concerns in
      residential facilities. PURPOSE: As there is no gold standard to assess when a
      client is unsafe, a two-phase study was conducted to develop client-centred
      guidelines for power mobility use. METHOD: In the first phase of the study,
      presented here, 18 in-depth, qualitative interviews were conducted with a variety
      of stakeholders, including power mobility users, other residents, staff and
      family members. RESULTS: A thematic analysis of the interviews revealed four main
      themes: 1) the meaning of power mobility, 2) learning the rules of the road, 3)
      red flags: concerns about safety, and 4) solutions. PRACTICE IMPLICATIONS: Given
      the importance of power mobility, safety measures need to address issues of
      mobility and safety for power mobility drivers and those around them.

PMID- 15988962
TI  - A web-based tutorial to enhance student learning of activity analysis.
AB  - BACKGROUND: This paper describes the impact on learning of a web-based tutorial
      for the application of activity analysis, with occupational therapy students, at
      McGill University, Montreal, Quebec. This tutorial offers unique, interactive
      instructional strategies allowing for self-directed higher cognitive and
      reflective learning, which has not been possible, to date, in current web-based
      technology. SCOPE: Through repeated practice, students collaboratively (in dyads)
      apply concepts of activity analysis, and receive immediate feedback by comparing
      their answers to a standard. METHODS AND RESULTS: Comparisons of performance
      outcomes on summative exams before and after implementation of the tutorial are
      made, suggesting a decrease in variance scores indicating fewer students are
      falling below the class average. These results are attributed to opportunities to
      practice activity analysis and to receive immediate feedback. PRACTICE
      IMPLICATIONS: Web-based instruction can impact student learning if the
      instructional strategies ensure coherence with all other instructional
      components, match the learning outcomes, facilitate self-directed and
      collaborative learning, and allow for practice and feedback.

PMID- 15988963
TI  - Social profile: assessment of validity and reliability with preschool children.
AB  - BACKGROUND: The Social Profile evaluates the social participation levels of
      children in activity groups and is based on the concepts of group social
      participation, interaction behavioural skills, and process factors. The 7 factors
      for each of the group levels in the Social Profile are cooperation, norms, roles,
      communication, activity behaviour, power and attraction. PURPOSE: This study
      evaluates the validity and reliability of the Social Profile. METHOD: A panel of
      eleven judges examined the content of the Social Profile and their
      recommendations were incorporated. Two occupational therapy observers measured
      group skills in 15 preschool groups of typically developing children. RESULTS:
      Cluster analysis of the study data indicated distinctions between skill clusters
      of social participation levels. Factor analysis confirmed these theoretical and
      clinical field component factors as distinct behaviours. CLINICAL IMPLICATIONS:
      The Social Profile has the potential to be used with a wide range of children to
      assess and treat their social skill deficits. Occupational therapy students and
      clinicians can use the assessment for training and to expand their observational
      abilities for evaluating social skills.

PMID- 15988964
TI  - It's the activity that counts: what clients value in psycho-educational groups.
AB  - BACKGROUND: This qualitative pilot research study provides client-centred
      outcomes by evaluating psycho-educational groups from the clients'perspective.
      PURPOSE: This study was designed to determine what clients value in three psycho
      educational groups offered in an acute inpatient psychiatric setting. METHODS:
      Interviews lasting 30 to 60 minutes relating to the 8 participants group
      experiences were recorded and transcribed verbatim. A constant comparative
      approach was used to analyze data allowing for both expected and emergent themes
      to be integrated into later interviews. RESULTS: Identified themes were group
      structure, readiness to attend groups and process information, and group milieu.
      Participants valued voluntary attendance and supportive milieu of groups.
      Insertion of relevant activity into groups to promote interaction, learning and
      information retention was also valued. PRACTICE IMPLICATIONS: Occupational
      therapists offering mental health groups should consider a number of factors.
      These include the importance of transitioning clients from activity groups to
      psycho-educational groups, as well as the value clients place in determining
      their readiness to attend a group and having a supportive milieu with limits to
      emotional disclosure.

PMID- 15988965
TI  - Canadian occupational therapists' contributions to prisoners of war in World War
      II.
AB  - BACKGROUND: A small number of Canadian occupational therapists provided materials
      to prisoners of war who were experiencing occupational deprivation in German
      camps during World War II. Although the occupational therapy contribution was
      relatively minor relative to the overall efforts of assistance to prisoners of
      war, it represented dedication, commitment and further sacrifice at a time when
      occupational therapists faced difficult choices. METHOD: An historical research
      method approach was employed to gather information from primary sources found in
      the Canadian Association of Occupational Therapy archives. Secondary sources were
      also consulted to provide additional background information. This paper outlines
      the need and context for the response, method of organization, materials sent,
      challenges experienced, and impact that this effort had on both POWs and the
      occupational therapists themselves. PRACTICE IMPLICATIONS: This account may
      inform and inspire current day occupational therapists who are considering the
      implications of occupational deprivation within frameworks of social and
      occupational justice.

PMID- 15988966
TI  - Meeting the responsibility that comes with the privilege: introducing a taxonomic
      code for understanding occupation.

PMID- 15988967
TI  - [Impact of tuberculosis morbidity on the health indices of a special contingent
      of the reformatory system].
AB  - The reformatory system of the Ivanovo Region shows a tense epidemic situation due
      to tuberculosis that heads the list of morbidity and ranks second in mortality in
      the region. 90-92% and 8-10% of new cases of tuberculosis occur in the
      reformatories and solitary confinements, respectively, the intracell morbidity in
      the solitary confinements being not more than 8.5-9%. Regular semiannual
      fluorographic examinations reveal that in the pattern of clinical forms of
      tuberculosis, its prevalent "small forms" (focal tuberculosis and infiltrative
      tuberculosis of 1-2 segments of one lung without decay) are prevalent.

PMID- 15988968
TI  - [Problems of tuberculosis in the penitentiary facilities of the Savatov Region
      and ways of their solution].

PMID- 15988969
TI  - [Problems in the identification and recording of patients with tuberculosis in
      investigatory solitary cells].
AB  - The analysis of the results of the detection, diagnosis, and recording of
      patients with active tuberculosis in an investigatory solitary cells of the
      Department of Penitentiary Facilities, Ministry of Justice of the Republic of
      Moldova, has revealed significant features that greatly differ not only from such
      a direction of work in the health care facilities, but also from other
      institutions (penal colonies, settlements) of this system. These features are
      associated with the specificity of the working conditions of investigatory
      solitary cells and mainly with the constant change of this contingent.

PMID- 15988970
TI  - [The tuberculosis situation in the penitentiaries of Buryatia and measures of its
      stabilization].
AB  - The paper presents the results of the tuberculosis situation in the
      penitentiaries of the Republic of Buryatia. It analyzes organizational measures
      for prevention of tuberculosis and its early detection in the prisoners and
      reflect the main reasons of the spread of tuberculous infection in the
      reformatories. The paper also shows the interdepartmental interactions of the
      medical service of the Ministry of Justice of the Russian Federation in the
      Republic of Buryatia with the Republican Tuberculosis Dispensary in notifying and
      controlling the patients who are in the reformatories, as well as the mechanisms
      of deporting the accused and convicts who suffer from tuberculosis.

PMID- 15988971
TI  - [Tuberculosis in the prisons of the Sverdlovsk Region].
AB  - In 1997 to 2002, the Sverdlovsk Region showed a reduction in the proportion of
      the accused and prisoners among adults and adolescents from 37.2 to 17.3% in the
      structure of tuberculosis morbidity and from 18.2 to 3.2% in that of its
      mortality. In 2003, prophylactic examinations revealed tuberculosis in 95% of the
      accused and prisoners. As compared with the general population, in adult and
      adolescent prisoners, morbidity due to tuberculosis was 8 times higher, its
      relapses were 9 times greater (early and late relapses being 28 and 3 times
      greater, respectively), its incidence was 9-fold and mortality, 1.3-fold.

PMID- 15988972
TI  - [Spread of multidrug resistance of Mycobacterium and its impact on the efficiency
      of treatment in patients with tuberculosis in the penitentiaries of the
      Arkhangelsk Region].
AB  - The paper deals with drug resistance of Mycobacterium tuberculosis in the prisons
      of the Arkhangelsk Region. The present study was undertaken to examine the spread
      of multidrug resistance of Mycobacterium tuberculosis and its impact on the
      outcomes of treatment of new cases of tuberculosis in the penitentiaries of the
      Arkhangelsk Region.

PMID- 15988973
TI  - [Tuberculosis control in the penitentiaries of the Republic of Belarus: state-of
      the-art and prospects].

PMID- 15988974
TI  - [Analysis of risk factors of the occurrence of drug resistance in patients with
      tuberculosis from civil and penitentiary sectors in the Samara Region].
AB  - The true prevalence rates of multidrug-resistant tuberculosis (MDRT) are unknown
      for most regions of Russia. This study was conducted in the Samara Region that
      differs from other regions in the rapid spread of HIV infection. The purpose of
      this study was to determine the primary and acquired resistance of Mycobacterium
      tuberculosis (MBT) to first-line antituberculous drugs in patients from civil and
      penitentiary sectors and to reveal risk factors of drug resistance of MBT. Six
      hundred patients (309 civilians and 291 prisoners who had been bacteriologically
      diagnosed as having tuberculosis. The authors have established the following:--in
      new cases, primary drug resistance is as follows: to isoniazid [38.9% (95% CI,
      31.3-36.9%)], to rifampicin [25.9% (95% CI, 19.4-33.4%)] and to MDRT [23.0% (95%
      CI, 16.7-30.3%)];--in prisoners, the primary resistance of MBT was statistically
      more significant than in civilians;--male sex, in adequate prior or current
      treatment for tuberculosis for more than 4 weeks, the presence of fibrocavernous
      tuberculosis and previous prison stay are essential risk factors of the
      development of resistance of MBT to both any first-line drug and MDRT;--HIV
      infection is unassociated with resistance.

PMID- 15988975
TI  - [Surgical aid to patients with respiratory tuberculosis].

PMID- 15988976
TI  - [Characterization of changes in the epidemiological tuberculosis situation in
      Russia on the basis of integral estimates].
AB  - The paper substantiates and provides evidence for that it is necessary to use
      summarized estimates to characterize the tuberculosis endemic situation. Some
      individual epidemiological indices are inadequately estimated to give a correct
      idea of epidemiological well-being. By using his own method for deriving an
      integral estimates, the author has analyzed the dynamics of the tuberculosis
      situation in Russia in 1985 to 2003. Two turning points have been established in
      the dynamics of the epidemic situation: 1) improvement up to 1991 inclusive and
      2) a subsequent deterioration up to 2002, thereafter the epidemic situation had
      tended to improve. A correlation matrix has been derived, which reflects a
      correlation of integral estimates with individual epidemiological indices.

PMID- 15988977
TI  - [Diagnostic features of recurrent respiratory tuberculosis].
AB  - In 1998-2001, prophylactic examinations revealed recurrences of respiratory
      tuberculosis in 70.1-69.8% of cases; among the persons having pronounced
      posttuberculosis changes, the recurrences being, on the contrary, detected in 61
      70% of cases on their visits to health care facilities for the symptoms of
      inflammatory bronchopulmonary disease. The recurrences of respiratory
      tuberculosis in the past years (1999-2001) are characterized by their predominant
      development in intact lung tissue and in the presence of minor residual
      tuberculosis-induced changes (64.8%) while those in the previous years (1991
      1993) occurred in 64.9% in the presence of pronounced residual changes. In 14.6%
      of patients, recurrent pulmonary tuberculosis are identified by detecting
      Mycobacterium tuberculosis in the sputum in the absence of clinical, X-ray, and
      laboratory data on the activity of residual tuberculosis-induced changes. Thus,
      18.7% and 19.6% of focal and infiltrative tuberculosis, respectively, and 66.7%
      of tuberculomas are detected. Common severe forms (disseminated, fibrocavernous,
      caseous pneumonia) are found in 66.7-100% of cases on referral to therapeutic
      institutions.

PMID- 15988979
TI  - [The Third Congress of the European Region of the International Union of
      Tuberculosis and Lung Diseases Control].

PMID- 15988978
TI  - [The cytogenic status of peripheral lymphocytes in pulmonary tuberculosis before
      and during chemotherapy].
AB  - The cytogenic status of peripheral lymphocytes was studied in 67 patients with
      drug-sensitive pulmonary tuberculosis. The latter was found to be attended by
      cytogenetic disorganization whose signs were present before and 2 months of
      intensive chemotherapy. In pulmonary tuberculosis, structural disorganization in
      the lymphocytic chromosomal apparatus was characterized by the elevated levels of
      cells and with changes in the structure and number of chromosomes. They are most
      pronounced in infiltrative and disseminated tuberculosis than in caseous
      pneumonia, as well as 2 months after rather than before chemotherapy. Patients
      with infiltrative pulmonary tuberculosis had also decreased lymphocytic activity
      of DNA reparation, followed by its normalization after a course of chemotherapy.

PMID- 15988980
TI  - [Clinical classification of extrapulmonary tuberculosis].
AB  - The authors propose a clinical classification of extrapulmonary tuberculosis,
      which is based on the standard reporting signs. They give the definitions of
      classification criteria established in any locations of tuberculous infection:
      etiology (tuberculosis, BCG infection, tuberculoallergic lesions), the extent and
      activity of a process with regard to clinical and morphological stages; bacterial
      isolation with consideration of the drug resistance of Mycobacteria; the nature
      of complications and sequels, etc. The characterization of local lesion includes
      the determination of organ-dependent clinical forms of tuberculosis; the type and
      form of complication; residual and sequels.

PMID- 15988981
TI  - Limitations of current proteomics technologies.
AB  - Application of proteomics technologies in the investigation of biological systems
      creates new possibilities in the elucidation of biopathomechanisms and the
      discovery of novel drug targets and early disease markers. A proteomic analysis
      involves protein separation and protein identification as well as
      characterization of the post-translational modifications. Proteomics has been
      applied in the investigation of various disorders, like neurological diseases,
      and the application has resulted in the detection of a large number of
      differences in the levels and the modifications of proteins between healthy and
      diseased states. However, the current proteomics technologies are still under
      development and show certain limitations. In this article, we discuss the major
      drawbacks and pitfalls of proteomics we have observed in our laboratory and in
      particular during the application of proteomics technologies in the investigation
      of the brain.

PMID- 15988982
TI  - Determination of UV-filter residues in bathing waters by liquid chromatography UV
      diode array and gas chromatography-mass spectrometry after micelle mediated
      extraction-solvent back extraction.
AB  - A preconcentration methodology utilizing the cloud point phenomenon is described
      in this study for the determination of sunscreen agent residues in bathing waters
      by reversed phase liquid chromatography with UV detection and gas chromatography
      (GC) with mass spectrometric (MS) detection. The method employs the entrapment of
      the analytes in the micelles of the non-ionic surfactant TX-114, upon increase of
      the solution temperature to 60 degrees C. The analytes are either re-extracted or
      back extracted from the final micellar extract into appropriate organic solvents,
      a procedure that facilitates the direct application of the method not only with
      liquid chromatography but mostly importantly with gas chromatographic analysis.
      Ultrasonication was employed to assist the procedure and accelerate the
      extraction of the analytes into the solvent phase. Under the optimum experimental
      conditions, the method affords satisfactory recoveries in the range of 95-102%
      and relative standard deviation lower than 6% without interference from the
      presence of the surfactant. The method was successfully applied to the
      determination of UV filters in natural waters.

PMID- 15988983
TI  - A first principles explanation for the experimentally observed increase in A-term
      band broadening in small domain silica monoliths and other chromatographic
      supports.
AB  - The present computational study illustrates how the existence of a residual lower
      limit on the variance of the skeleton and through-pore size of monolithic columns
      can be expected to severely compromise the possibility to prepare well-performing
      small domain monolithic columns. Adopting rather conservative estimates for the
      minimal standard deviation on the pore and the skeleton size (0.2 and 0.04
      microm, respectively), the presented calculations show that, if such a fixed
      lower limit on the size variance exists, it will be impossible to decrease the A
      term band broadening below a given critical value, no matter how small the domain
      size is made. From a given critical domain size value on, any attempt to further
      decrease the domain size without being able to co-reduce the size variance can be
      expected to be counterproductive and leads to an increase instead of to a further
      decrease of the plate heights.

PMID- 15988984
TI  - Determination of [S,S']-ethylenediamine disuccinic acid (EDDS) by high
      performance liquid chromatography after derivatization with FMOC.
AB  - The paper describes a new HPLC method for the determination of ethylenediamine
      disuccinic acid (EDDS). EDDS is derivatized with FMOC reagent followed by HPLC
      separation on a reversed-phase column. The eluents consist of phosphate buffer at
      pH 6.8 and acetonitrile. Separation was carried out using gradient elution. The
      FMOC-EDDS derivative is detected with a fluorescence detector with an excitation
      wavelength of 265 nm and an emission wavelength of 313 nm. The detection limit is
      0.01 microM. The method is applicable to the determination of the compound in
      water, soil solution and plant material at trace levels.

PMID- 15988985
TI  - Development and optimization of a method for the analysis of Brazilein by HPLC
      with electrochemical detection.
AB  - The aim of this study was to establish an easy and accurate method for the
      determination of Brazilein in plant samples due to its potential pharmacological
      activities. High-performance liquid chromatography (HPLC) with electrochemical
      detection (ED) was used for the assay of Brazilein in this study for the first
      time. Crucial influence parameters including concentration of dodecane-1-sulfonic
      acid sodium salt (DSASS), inorganic modifier, tetrabutyl-ammonium hydroxide
      solution (TBAOH), and applied potential of proposed method were investigated. The
      proposed method is simple, rapid (analysis time: approximately 10 min), sensitive
      [(detection limit: 0.6 ng per injection (20 microl) at a signal-noise ratio
      3:1)], highly selective and precise (intra- and inter-day precisions were within
      5%, n = 7). The calibration graph of Brazilein was linear in the range 0.6-150 ng
      per injection 20 microl. Recovery of Brazilein was over 92% by standard addition
      method.

PMID- 15988986
TI  - Automated solid-phase extraction and high-performance liquid chromatographic
      determination of nitrosamines using post-column photolysis and tris(2,2'
      bipyridyl) ruthenium(III) chemiluminescence.
AB  - A sensitive and selective post-column detection system for nitrosamines is
      described. The principle upon which the detector works is that UV irradiation of
      aqueous solutions of nitrosamines leads to cleavage of the N-NO bond. The amine
      generated is subsequent detected by chemiluminescence using tris(2,2'-bipyridyl)
      ruthenium(III), which is on-line generated by photo-oxidation of the
      ruthenium(II) complex in the presence of peroxydisulfate. Factors affecting the
      photochemical and chemiluminescent reactions were optimized to minimise their
      contribution to the total band-broadening. This detection system was tested for N
      nitrosodimethylamine, N-nitroso-diethylamine, N-nitrosomorpholine, N
      nitrosopiperidine and N-nitrosopyrrolidine, which were separated on an ODS column
      by isocratic reversed-phase chromatography with acetonitrile-water containing 5
      mM acetate buffer at pH 4.0. A linear relationship between analyte concentration
      and peak area was obtained within the range 0.13-500 microg l(-1) with
      correlation coefficients greater than 0.9995 and detection limits of between 0.03
      and 0.76 microg l(-1). Intra- and inter-day precision values of about 1.2% RSD (n
      = 11) and 2.5% RSD (n = 10), respectively, were obtained. The sensitivity may
      increase from 9 to 280 times with respect to UV detection, depending on the
      nitrosamine in question. An automated solid-phase extraction (SPE) system was
      used in conjunction with HPLC to determine nitrosamine residues in waters.
      Detection limits within the range 0.10-3.0 ng l(-1) were achieved for only 250 ml
      of sample.

PMID- 15988988
TI  - Determination of chlorinated toluenes in raw and treated water samples from the
      Llobregat river by closed loop stripping analysis and gas chromatography-mass
      spectrometry detection.
AB  - A study of the occurrence of chlorinated toluenes in Llobregat river (NE Spain)
      has been carried out. These compounds are currently being used in local textile
      industries as dye carriers and have replaced the common trichlorobenzene
      mixtures. Closed loop stripping analysis (CLSA), routinely used to monitor the
      quality of river water for a broad range of volatile compounds, has been employed
      as an analytical tool to determine them at ng/L levels in wastewater and textile
      industry effluents and also in raw and treated water from two drinking water
      treatment plants situated in the river course. The CLSA extracts were analyzed by
      HRGC/MS. Ring halogenated dichloro- and, to a lesser extent, mono- and
      trichlorotoluenes have been identified. These compounds have not been reported to
      our knowledge as common water pollutants.

PMID- 15988987
TI  - Location of double bonds in diene and triene acetates by partial reduction
      followed by methylthiolation.
AB  - Two random reduction procedures (NH2NH2/H2O2 and NH2NH2/O2) were compared and
      conditions optimized for the reduction of two synthetic pheromone compounds
      (9Z,11E)-9,11-tetradecadienyl acetate and (9Z,12E)-9,12-tetradecadienyl acetate
      on a 300 microg scale at 60 degrees C. The relative amounts of the four products
      (completely reduced acetate, unreacted diene acetate and two monoene acetates),
      characterized by gas chromatography (GC) from the reaction mixture, depended on
      the reaction conditions. The reduction was straightforward without any detectable
      undesired side products. The reaction yields were reproducible with both the
      reducing reagents. The optimized reduction conditions thus established were
      utilized to reduce seven synthetic compounds (four diene and three triene
      acetates) on a micro scale (5 microg). In all cases, expected compounds were
      identified by GC-MS. After reduction, two methods were used to locate the
      position of double bonds in the partially reduced compounds. In the first method,
      the products from the above seven compounds were isolated by extraction with
      hexane and reacted with dimethyl disulfide to give the DMDS adducts. In the
      second method ("one-pot"), the reduced compounds were not isolated but instead,
      the solvents were evaporated and the DMDS derivatives formed. In both cases,
      determination of the position of the double bonds was possible by GC-MS analyses.
      The complete procedure (reduction and DMDS derivative formation) could be carried
      out on a 100 ng scale. Although neither of the partial reduction methods offered
      significant advantages over the other, partial reduction with NH2NH2/H2O2 was
      more convenient and hence should be the method of choice, together with DMDS
      derivative formation to locate double bonds in pheromones. In addition, a new
      procedure is described using ND2ND2/H2O2 and DMDS derivative formation capable of
      distinguishing between the double bond positions in (Z)-9-tetradecenyl acetate
      and (9Z,12E)-9,12-tetradecadienyl acetate (1:1 mixture).

PMID- 15988989
TI  - Determination of partition behavior of organic surrogates between paperboard
      packaging materials and air.
AB  - The suitability of recycled paperboard packaging materials for direct food
      contact applications is a major area of investigation. Chemical contaminants
      (surrogates) partitioning between recycled paper packaging and foods may affect
      the safety and health of the consumer. The partition behavior of all possible
      organic compounds between cardboards and individual foodstuffs is difficult and
      too time consuming for being fully investigated. Therefore it may be more
      efficient to determine these partition coefficients indirectly through
      experimental determination of the partitioning behavior between cardboard samples
      and air. In this work, the behavior of organic pollutants present in a set of two
      paper and board samples intended to be in contact with foods was studied.
      Adsorption isotherms have been plotted and partition coefficients between paper
      and air have been calculated as a basis for the estimation of their migration
      potential into food. Values of partition coefficients (Kpaper/air) from 47 to
      1207 were obtained at different temperatures. For the less volatile surrogates
      such as dibutyl phthalate and methyl stearate higher Kpaper/air values were
      obtained. The adsorption curves showed that the more volatile substances are
      partitioning mainly in air phase and increasing the temperature from 70 to 100
      degrees C their concentrations in air (Cair) have almost doubled. The analysis of
      surrogates was performed with a method based on solvent extraction and gas
      chromatographic-flame ionization detection (GC-FID) quantification.

PMID- 15988990
TI  - Characterisation of natural polysaccharides (plant gums) used as binding media
      for artistic and historic works by capillary zone electrophoresis.
AB  - The monosaccharide constituents of plant gums were separated by capillary
      electrophoresis at pH 12.1 and detected with indirect UV absorbance. The plant
      gums investigated were gum arabic, gum acacia, gum tragacanth, cherry gum and
      locust bean gum (carob gum). The monosaccharides obtained after hydrolysis with
      2M trifluoroacetic acid and lyophilisation of the hydrolysate were arabinose,
      galactose, mannose, rhamnose, xylose, fucose, and glucose, and the two sugar
      acids galacturonic and glucuronic acid, in accordance with the literature. They
      were separated in a background electrolyte consisting of NaOH to adjust the pH,
      20 mM 2,6-pyridinedicarboxylic acid as chromophore for detection and 0.5 mM
      cetyltrimethylammonium bromide as additive to reverse the electroosmotic flow.
      Based on their electropherograms, the plant gums could be identified by their
      typical composition (depicted in a decision scheme) as follows: a peak of
      glucuronic acid, together with that of rhamnose, is indicative for gum arabic.
      Peaks of galacturonic acid and fucose point to gum tragacanth. Locust bean gum
      shows a major peak for mannose (with the concomitant galactose peak in ratio 4
      1), whereas a glucuronic acid and a mannose peak together with a prominent
      arabinose peak indicates cherry gum. The method was applied to identify the plant
      gums in samples like watercolours and in several paint layers like gum tempera or
      those with egg white or drying oils as additives. Artificial aging experiments of
      thin layers of gum arabic on paper or glass carried out with UV-A radiation (366
      nm) did not result in changes of the saccharide patterns, in contrast to the
      simultaneously conducted aging of a drying oil layer.

PMID- 15988991
TI  - Determination of ephedrine alkaloid stereoisomers in dietary supplements by
      capillary electrophoresis.
AB  - Three complementary capillary electrophoresis (CE) methods were developed for the
      separation and quantification of ephedrine and pseudoephedrine stereoisomers.
      Either single or dual cyclodextrin-based chiral selector systems provided
      enantioselective separation of the compounds of interest. The three methods were
      applied to the analysis of a suite of five standard reference materials (SRMs)
      containing ephedra. Use of a high-sensitivity UV detection cell enhanced
      quantification of the analytes of interest over the wide range of concentrations
      encountered in the SRMs. Results for (-)-ephedrine ranged from 0.31 to 76.43
      mg/g, and for (+)-pseudoephedrine ranged from 0.049 to 9.23 mg/g in the materials
      studied. Results from the three methods agreed well with each other and with the
      results from other methods of analysis. The addition of known amounts of specific
      enantiomers was used to confirm the enantiomeric identity of the analytes. The
      results obtained by the three CE methods were utilized for value assignment of
      the ephedrine alkaloid content of these five SRMs.

PMID- 15988992
TI  - Purification of astilbin and isoastilbin in the extract of smilax glabra rhizome
      by high-speed counter-current chromatography.
AB  - Purification of astilbin from the rhizome extract of Smilax glabra was conducted
      using a high-speed counter-current chromatograph equipped with a 700 mL column.
      In a single operation, 1.5 g of crude sample was separated to yield 105 mg of
      component astilbin and 48 mg of isoastilbin while the upper phase of the two
      phase solvent system composed of n-hexane-n-butanol-water (1:1:2, v/v/v) was used
      for stationary phase. The chemical structures of the two flavonoid glycosides
      were confirmed by electrospray ionization ion trap multiple mass spectrometry and
      nuclear magnetic resonance experiments.

PMID- 15988993
TI  - [Chief therapists of the fronts and Navy in the Great Patriotic War (1941-1945)].

PMID- 15988994
TI  - [Outstanding figures of the USSR Navy--admiral N.G. Kuznetsov and academician of
      the USSR Academy of Medical Sciences A.L. Myasnikov].

PMID- 15988995
TI  - [Medical problems of the Great Patriotic War (1941-1945)].

PMID- 15988996
TI  - [Trends in the rheumatic diseases morbidity in the Russian Federation population
      for 1999-2003].

PMID- 15988997
TI  - [Evaluation of rheumatoid arthritis activity in clinical practice].
AB  - AIM: To develop inflammatory activity index (IAI) for assessment of rheumatoid
      arthritis (RA) activity in wide clinical practice. MATERIAL AND METHODS:
      Leflunomide was given to 414 patients for 18.4 +/- 5.7 weeks, on the average. The
      assessment of the drug efficacy was made by arthralgia severity according to
      visual analog scale (VAS), duration of morning stiffness, the number of painful
      joints at palpation, number of swollen joints (NSJ), general condition (GC) of
      the patient, ESR. DAS28 was used as a basic indicator of the disease activity and
      efficacy. IAI was formed on the basis of DAS28 and 3 baseline components--NSJ (28
      joints), GC and ESR. RESULTS: DAS28 and IAI significantly correlated (r = 0.87, p
      < 0.01). Comparison of pairs of these indices can specify ranges of IAI
      corresponding to high, moderate and low RA activity in assessment by DAS28.
      CONCLUSION: IAI is a simple and reliable index of RA activity in clinical
      practice.

PMID- 15988998
TI  - [Clinical and laboratory markers of immune dysfunction in patients with
      rheumatoid arthritis and their blood relatives].
AB  - AIM: To ascertain clinical and laboratory signs of immune disorders in patients
      with rheumatoid arthritis (RA), their healthy blood relatives and healthy females
      without autoimmune disease family history. MATERIAL AND METHODS: Immune status
      was studied in 66 RA patients, their 56 female relatives of the first and 10
      female relatives of the second degree of kinship, 63 healthy females without
      family history of autoimmune disorders. Immune response was assessed
      conventionally. RESULTS: 87.5% relatives of the first degree had symptoms of
      immune dysfunction (control--50.8%). Combinations of immunopathological syndromes
      were registered in 41.1% examinees of this group (control--17.5%). Autoimmune
      syndrome was most frequent (64.3%, control--19%). Infectious syndrome occurred in
      51.8% relatives and 33.3% controls (the difference is significant). Despite
      immunosuppressive therapy, occurrence of infectious syndrome in RA (18.6%) was
      much lower than in controls. It was found that before RA onset 81.4% patients
      suffered from frequent long-term infections. RA onset reduced the infections
      frequency. Allergy was in 12.5, 19 and 6.2% of the relatives, controls and
      patients, respectively. The relatives demonstrated a significant decline of
      compliment activity close to such in patients. CONCLUSION: Immune disorders in
      blood relatives of women suffering from RA are more frequent and severe than in
      women without autoimmune disorders in family history. However, subclinical
      immunopathological symptoms in them did not realize in certain disease during the
      observation period. This may be explained by weaker congenital defects of immune
      system functioning or the existence of compensatory mechanisms suppressing
      development of pathological autoimmune processes.

PMID- 15988999
TI  - [Rheumatoid arthritis: family and disease].

PMID- 15989000
TI  - [Experience in long-term therapy of active rheumatoid arthritis with
      leflunomide].
AB  - AIM: To study therapeutic potential of a novel basic drug leflunomide in
      suppression of activity and progression of rheumatoid arthritis (RA). MATERIAL
      AND METHODS: Leflunomide efficacy was investigated in a 36 month trial including
      50 patients with moderate and high activity RA. Monthly registrations were made
      of the articular syndrome quantitative parameters (Richi's index, number of
      painful and swollen joints, severity of pain and general condition of the
      patient), morning stiffness duration, ESR, CRP, RF. Leflunomide efficacy was
      assessed by EULAR and ACR criteria. Dynamics of the extrajoint manifestations
      observed in 70% patients before therapy were examined clinically and by device
      tests. Speed of progression of erosive arthritis was quantified by a modified
      Sharp's method in hand and foot joints, carpal bones each 6 months. Arava
      tolerance was controlled clinically and by laboratory tests. RESULTS: Leflunomide
      was found effective in 94% RA patients. A rapid (within the first month) and
      significant improvement in parameters of articular syndrome and CRP level was
      observed. To month 4 of therapy 1/5 patients achieved remission by EULAR
      criteria, to month 12--1/3 patients. By ACR criteria, 6-month leflunomide
      treatment produced good and exellent results in 71% patients which persisted up
      to the 36th month of therapy. The effect was better in shorter history of RA,
      moderate RA, in the absence of osteolyses and ankyloses. Leflunomide
      significantly reduced RF concentration in the serum, suppressed extrajoint RA
      manifestations (except Sjogren's syndrome). The mean number of new joint erosions
      for 6 consecutive months was 2.93 +/- 3.2, 1.41 +/- 1.8, 0.78 +/- 2.0 (median 0),
      while progression coefficient corresponded to slow progression to the treatment
      month 18. No new erosions occurred after 12 months of arava treatment in 41%
      patients and after 18 months--in 62%. CONCLUSION: Leflunomide is well tolerated.
      The drug was discontinued because of cutaneous pruritus and diarrhea in 5 and 1
      patients, respectively.

PMID- 15989001
TI  - [Vascular symptoms of Behcet's disease].
AB  - AIM: To characterize vascular symptoms of Behcet's disease (BD) in patients
      treated for the last 10 years in the Institute of Rheumatology. MATERIAL AND
      METHODS: Vascular symptoms of BD were studied in 151 patients with BD (mean age
      33.5 +/- 9.5 years, duration of the disease 14.0 +/- 10.1 years, 104 males and 47
      females, 67.4% carried HLA B51(5) antigen). Duplex vascular scanning was made to
      detect venous thrombosis. RESULTS: Thrombotic complications were found in 37 of
      151 (24.5%) patients with BD (30 males and 7 females, mean age 37.1 +/- 9.1
      years, mean duration of the disease 7.3 +/- 9.7 years). Venous thromboses
      prevailed (36 patients). Four males (2.6%) had arterial lesions: aneurysms of the
      iliac arteries (n = 1), thrombosis of the iliac artery (n = 1), pulmonary
      infarction and thrombosis of the pulmonary arteries (n = 2). Combination of
      venous and arterial manifestations occurred in 3 patients. One patient had
      thrombosis of the venous sinus, occlusion of the retinal vessels was diagnosed in
      7 patients. CONCLUSION: Incidence of vascular disorders was observed in 1/4 of
      the patients. This corresponds to those observed worldwide and concerns venous
      thrombosis and other thromboses. Among the examinees, vascular disorders were
      associated with a young age, earlier development of thrombotic complications in
      males than in females.

PMID- 15989002
TI  - [Catastrophic antiphospholipid syndrome: diagnosis and treatment].
AB  - AIM: To analyse data on patients who developed catastrophic antiphospholipid
      syndrome (CAPS) in primary and secondary APS, to assess outcomes of CAPS.
      MATERIAL AND METHODS: We analysed retrospectively the data on 164 patients with
      systemic lupus erythematosus (SLE) and APS, on 76 patients with primary APS
      (PAPS) treated in the Institute of Rheumatology from 1989. Verification of
      vascular complications was made using ultrasonic dopplerography (UDG) of
      peripheral vessels, echocardiography of the heart, CT of the brain, abdominal
      organs. Anticardiolipin antibodies (ACLab) and lupus anticoagulant (LA) served as
      serological markers of APS. RESULTS: In the observation period of 9.4 +/- 4.2
      years, 33 patients (23 females and 10 males) out of 164 patients with SLE+APS
      developed CAPS, 8 of them survived while 25 died. CAPS patients had no
      differences by age, duration of the disease, its activity and symptoms from
      patients who had no CAPS. Ten out of 76 patients with PAPS developed CAPS, 7 of
      them died. The analysis of the concomitant factors which may initiate PAPS showed
      that in SLE and APS these factors consisted of initial menopause (n = 2),
      infection (n = 12), including pneumonia (n = 7), acute respiratory disease (n =
      3), food poisoning (n = 1), abscess (n = 1). Cancer was in one patient, trauma
      after road accident in one patient. Trigger factor was not determined in 13
      patients. In PAPS provoking factors were pneumonia (n = 2) and abscess (n = 1),
      in 7 patients these factors were not detected. CONCLUSION: Any infection in SLE
      patients should be adequately treated with antibiotics; APS patients treated
      surgically should receive parenteral anticoagulants instead of oral ones;
      puerperas with APS must receive adequate parenteral anticoagulant therapy for at
      least 6 weeks; in exacerbation of SLE, APS patients should receive parenteral
      anticoagulants with following hypocoagulation with oral anticoagulants.

PMID- 15989003
TI  - [Antiphospholipid syndrome in the structure of hematogenic thrombophilia in young
      and middle-aged patients with venous thrombosis].
AB  - AIM: To specify detectability and clinical presentation of antiphospholipid
      syndrome (APS) in young and middle aged patients with phlebothromboses (PT).
      MATERIAL AND METHODS: Enzyme immunoassays for lupus anticoagulant, PCR
      determination of G1691A mutation in the gene of coagulation factor V, mutation
      G20210A in prothrombin gene, mutation C677T in methylenetetrahydrofolate
      reductase (MTHFR) gene were made in 97 patients (57 males and 40 females) with
      venous thrombosis as well as estimation of external and internal coagulation,
      antithrombin III activity, protein C activity, plasma fibrinogen, stimulated
      platelet aggregation, blood and plasma viscosity. RESULTS: APS was detected in
      20.6% young and middle-aged patients with venous thrombosis, in 18.5% of them-
      primary APS. In APS patients acquired risk factors of thrombosis occurred
      significantly less frequently than in patients with venous thrombosis free of APS
      (30 and 70%, respectively). Recurrent pulmonary artery thromboembolism (TEPA)
      prevailed in APS patients. In patients with combined hemostatic disturbances
      (APS+mutation) TEPA was diagnosed more frequently than in APS patients and in the
      absence of markers of genetic thrombophilia. Plasma viscosity is most important
      diagnostically among rheological indices.

PMID- 15989004
TI  - [Classification of microangiopathy in systemic sclerosis].
AB  - AIM: To classify main types of morphological changes of nailfold capillaries in
      systemic sclerosis (SSc). MATERIAL AND METHODS: Nailfold videocapillaroscopy
      (NCS) was performed in 103 patients with SSc (34 patients with dSSc and 69
      patients with ISSc) with a median age of 47.9 +/- 13.3 years and mean disease
      duration of 8.1 +/- 7.1 years. The control group consisted of 35 healthy persons.
      RESULTS: On the basis of a quantitative estimation of changes the main
      capillaroscopic patterns of structural changes of capillaries in SSc were
      distinguished. The first (early) type is characterized by changes mainly of sizes
      of capillaries and a rather moderate decrease of their amount. In the second
      (transitive) type simultaneously with change of the sizes of capillaries an
      appreciable decrease of the amount of capillaries with formation of avascular
      sites is observed. The third (late) type of changes is characterized by marked
      reduction of capillaries and plenty of avascular sites in the absence or presence
      of few dilated capillaries. NCS enables to reveal destruction and new growth of
      capillaries. The statistical analysis has shown authentic distinctions of NCS
      parameters between main types of changes and close association of these types
      with activity of the disease. CONCLUSION: Definition of a type of capillaroscopic
      changes can serve a reliable and objective criterion of a stage and activity of
      microangiopathy in SSc which reflects duration of illness as a whole.

PMID- 15989005
TI  - [Effective treatment of systemic sclerosis with leflunomide].

PMID- 15989006
TI  - [Severity of a female gout course].
AB  - AIM: Comparison of a gout course in males and females. MATERIAL AND METHODS: The
      trial enrolled 34 patients (17 females and 17 males). The patients were matched
      by age and the disease duration. Severity of a gout course was assessed by the
      disease history, articular syndrome, concomitant diseases, blood biochemistry.
      Statistical processing was made with a computer program "Statistica 6.0".
      RESULTS: Events predisposing to purin metabolism disturbances and, therefore, to
      development of gout occur more frequently in females than in males. For the most
      part this concerns arterial hypertension and intake of diuretics. Women often
      have endocrine pathology (artificial menopause, dysmenorrhea, euthyroid goiter).
      In women gout runs a more severe course manifesting in early chronization,
      polyarticularity, lingering arthritis, rapid formation of tophuses. Both groups
      demonstrated marked polymorbidity with accumulation of the diseases related to
      atherosclerosis. Distinct group differences by content of uric acid seem to arise
      from early onset of chronic renal failure in women. CONCLUSION: In the absence of
      sex- and age-related differences, a more severe course of gout is observed in
      women. This may be due to hyperuricemia and a trend to the disease chronization,
      high prevalence of arterial hypertension and renal failure.

PMID- 15989007
TI  - [Markers of vascular endothelium activation in gout].
AB  - AIM: To determine clinical significance of laboratory markers of vascular
      endothelium activation in gout. MATERIAL AND METHODS: A total of 16 males aged 31
      68 years with gout entered the study. The diagnosis satisfied Vallas' criteria,
      duration of the disease varied from 1.5 to 14 years. Six (37%) patients had
      chronic gouty arthritis, ten (63%) patients were in the attack-free period. All
      the patients had metabolic syndrome, 7 (43.7%) of them suffered from diabetes
      mellitus type 2. Arterial hypertension was diagnosed in 12 (75%) patients.
      Thickness of the intima-media complex (IMC) of the carotid arteries was measured
      in 12 patients with duplex ultrasonic scanning. Solid phase enzyme immunoassay
      studied serum concentrations of a soluble form VCAM-1 (sVCAM-1) and von
      Willebrand factor antigen (WF:Ag) as laboratory markers of endothelial
      activation. The above immunoassay was also used to study acute phase inflammatory
      changes by the levels of C-reactive protein (CRP). RESULTS: Concentration of
      sVCAM-1 in gout was 1385.2 +/- 341.0 ng/ml and was significantly higher than in
      the control group (p < 0.001). Mean values of WF:Ag and CRP in the serum were
      also significantly higher in the study group. The levels of both sVCAM-1 and
      WF:Ag were elevated in 25% patients. CRP was elevated (8 mg/l) in 6 (37.5%)
      patients. They had no infectious complications and age-, duration- and stage
      related specific features of the disease. There was no significant differences
      between mean levels of sVCAM-1, WF:Ag, CRP in patients with diabetes mellitus and
      metabolic syndrome. There was no correlation between uric acid level and IMC
      thickness (r = 0.12; p > 0.05). A weak positive insignificant correlation was
      found between concentration of CRP, sVCAM-1 and IMC thickness of the carotid
      arteries (r = 0.28 and r = 0.36, respectively; p > 0.05). However, this index
      significantly correlated with WF:Ag(r = 0.62; p < 0.05). A moderate positive but
      insignificant correlation was detected between the levels of sVCAM-1 and WF:Ag (r
      = 0.47; p > 0.05). Concentration of sVCAM-1 weakly correlated with that of CRP (r
      = 0.35; p > 0.05). WF:Ag and CRP levels correlated significantly (r = 0.51; p <
      0.05). CONCLUSION: Increased concentrations of sVCAM-1 and WF:Ag in gout reflect
      not only activation of vascular endothelium but also development of
      atherosclerotic process in these patients.

PMID- 15989008
TI  - [Incidence rates of articular pain in urban and rural population of Russia
      (preliminary data)].
AB  - AIM: Screening of the population sample for articular pain and swelling. MATERIAL
      AND METHODS: A screening questionnaire for detection of arthritides and
      arthralgias was filled in for each adult rural and urban citizen aged over 18
      years from 15 RF regions. Rural population was covered with a complete
      examination, urban one was examined by formation of a representative sample from
      general population. The screening covered a total of 31424 persons, mean age of
      whom was 47.6 +/- 17.6 years. Among them 14001 lived in the cities and 17423 in
      the villages. 61% respondents were women. RESULTS: Prevalence of arthralgias in
      the population reaches 46%. While the symptoms alleviated with time in 8%, they
      became chronic in the rest. The articular complaints rate in the population is
      sex-related and depends on the age. In persons under 20 years arthralgia occurs
      in 9%. Urban citizens have articular pains more frequently than rural population-
      43 and 33%, respectively. CONCLUSION: Pilot results of the screening program
      demonstrate prevalence of arthralgias in Russia and the importance of joint
      pathology problem in Russia.

PMID- 15989009
TI  - [Gastroduodenal safety of selective inhibitors of cyclooxigenase-2: practical
      validation].
AB  - AIM: To evaluate rate of erosions and ulcers of the upper gastroduodenal tract
      (UGDT) in patients treated with selective cyclooxigenase inhibitors (C-NAID).
      MATERIAL AND METHODS: A retrospective analysis of esophagogastroduodenoscopies
      made in the Institute of Rheumatology in 2002-2004 was made for two groups. The
      study group received C-NAID (nimesulid, n = 330; meloxicam, n = 371; celecoxib, n
      = 66), the control group--diclofenak (n = 1935). The groups were matched by age,
      gender and concomitant therapy. Incidence of ulcers in the past was significantly
      higher in the study group. RESULTS: Occurrence of erosions and ulcers in the
      study and control groups was comparable: 22.4, 24.5, 21.2 and 27.6%,
      respectively. Multiple erosions (ME, n > 10) and ulcers significantly less
      frequently occurred in the study group: 8.8, 10.5, 10.6 and 14.6%, respectively
      (p < 0.05). Significant difference in occurrence of erosions and ulcers in UGDT
      for different C-NAID was not found. ME and ulcers in patients with ulcer
      anamnesis were recorded less frequently in intake of C-NAID than diclofenak (22.5
      and 46.2%, resopectively, p < 0.001). CONCLUSION: Selective inhibitors of COG-2
      are not safe enough in relation to gastrointestinal pathology, especially in
      patients with ulcer anamnesis. Nimesulid, meloxicam and celecoxibe were
      comparable in respect to detectability of gastrointestinal erosions and ulcers.

PMID- 15989010
TI  - [Unwanted reactions to modifying antirheumatic drugs].
AB  - AIM: To specify causes of discontinuation of the disease-modifying antirheumatic
      drugs (DMAD) used in rheumatoid arthritis (RA) by the results of special
      questionnaire survey. MATERIAL AND METHODS: The study included 298 RA patients
      treated in the Institute of Rheumatology (34 males and 264 females aged 18-82,
      mean age 54.6%, duration of the disease 1 to 38 years, mean 10.7 years) who
      responded to questioning. RESULTS: The following DMAD were used: metotrexate (n =
      137), sulfasalasine (n = 49), aminoquinoline drugs (n = 33), chlorbutin (n = 19),
      azathioprin (n = 13), tauredon (n = 11), cyclophosphamide (n = 5). The drugs were
      discontinued due to unwanted effects in 50, 10, 46, 9, 4, 3, 3 (methotrexate,
      sulfasalasin, aminoquinolines, chlorbutin, azathioprin, Ag salts,
      cyclophosphamide, respectively). Cyclophosphamide and chlorbutin appeared most
      toxic, while sulfasalasine and aminoquinolines were found least effective.
      CONCLUSION: DMAD discontinuation rate ranges from 12.1% (aminoquinolines) to 60%
      (cyclophosphamide), mean 31.1%.

PMID- 15989011
TI  - [Drug disease: is it iatrogeny?].
AB  - AIM: To draw attention of medical professionals to the problem of side effects of
      medication. MATERIAL AND METHODS: Analysis of evolution of views on unwanted
      effects of the drugs. RESULTS: The authors hold that the problem of side effects
      of many drugs is underestimated in Russia as relevant information is scare.
      CONCLUSION: Detection of side effects of the drugs allows conduction of
      prophylactic measures.

PMID- 15989012
TI  - [Ischemic postconditioning of the myocardium: a new method of heart protection
      against reperfusion damage].
AB  - AIM: To examine effects of ischemic postconditioning on persistent ventricular
      fibrillation (VF) induced by reperfusion on the model of isolated rat heart.
      MATERIAL AND METHODS: Isolated by Langendorf hearts (n = 46) were ischemized for
      30 min with following reperfusion. Hearts with persisting VF (n = 11) persisting
      to reperfusion minute 15 were randomized into two groups: control (n = 6)-
      reperfusion without interventions, study group on postconditioning (n = 5)--2 min
      global ischemia followed by reperfusion. Left ventricular pressure, heart rate,
      coronary blood flow were registered continuously. RESULTS: VF converted to a
      regular rhythm in all the hearts exposed to postconditioning. Regular
      contractions were made by all the postconditioned hearts in the course of further
      reperfusion. None of the control hearts had normal rhythm in the end of the
      experiment. In the end of reperfusion pulse left ventricular pressure of the
      postconditioned hearts was lower than that in hearts without persistent VF.
      CONCLUSION: Ischemic postconditioining exerts an arrhythmic effect in relation to
      persistent reperfusion ventricular tachyarrhythmias. Postconditioning may serve a
      new strategy for myocardial protection.

PMID- 15989013
TI  - [Comparison of noliprel and caposide efficacy in patients with arterial
      hypertension of high risk].
AB  - AIM: To compare clinical efficacy and tolerance of fixed combinations of
      perindopril and indapamide (noliprel), capoten+hydrochlorotiaside (caposide) in
      arterial hypertension stage I-II of high and very high risk which failed prior
      monotherapy. MATERIAL AND METHODS: A blind randomized trial in parallel groups
      recruited 40 patients (20 patients each). The patients received 1 tablet a day
      noliprel (2 mg/0.625 mg) or caposide (50 mg/25 mg) for 6 months. Target pressure
      patients were counted. Speed of the pulse wave, blood lipids and electrolytes,
      left ventricular myocardium posterior wall thickness were estimated. RESULTS: By
      antihypertensive efficacy and ability to reduce left ventricular hypertrophy and
      to improve arterial elasticity, low-dose fixed combination (noliprel) was not
      inferior to caposide (high-dose fixed combination) while by T/P noliprel was more
      effective than caposide, it lowered cholesterol more but potassium level--less.
      CONCLUSION: Noliprel has the the same with caposide antihypertensive efficacy and
      ability to diminish LVH. It has benefits by action on lipid and electrolyte
      indices.

PMID- 15989014
TI  - [Knee joint osteoarthrosis: updated approach to treatment].

PMID- 15989015
TI  - [Aceclofenac (aertal) in rheumatological practice].

PMID- 15989016
TI  - [Current ideas about factors responsible for renal damage in gout].

PMID- 15989017
TI  - [Comparative assessment of urological, neurological, obstetric, and gynecological
      risk factors of urinary incontinence in women].
AB  - To compare the effects of urological, neurological and obstetricogynecological
      risk factors of urine incontinence (UI) in women, we made a questionnaire survey
      covering a representative sample of 4336 female residents of Moscow aged 25-74
      years. We used standard epidemiological methods and unified criteria, descriptive
      statistics and modeling by means of logical regression in 6.12 version of SAS
      system. We revealed that chronic cystitis and other inflammatory urinary diseases
      provoke a 4-fold increase in the relative risk (RR) of UI in women being higher
      than obstetricogynecological risk factors (RR 1.5-2.8) and neurological risk
      factors (RR 1.3-2.0). UI in many cases is of stress type, but in urinary
      inflammation a mixed type occurs 1.8 times more frequently. Thus, chronic
      cystitis and other urinary inflammatory diseases are essential UI risk factors in
      women.

PMID- 15989018
TI  - [Morphometic characteristics of the kidneys in peritonitis].

PMID- 15989019
TI  - [Correction of ureteropelvic segment stenosis by Kuchere: the operative technique
      and results].
AB  - Efficacy of surgical correction of stenosed pelviureteral segment (SPS) in 30
      patients with hydronephrosis was analysed. Twenty three patients have undergone
      extended resection of the extrarenal pelvis together with SPS. Repair of the
      pelviureteral segment in these patients was made by Kuchere technique. Histologic
      examination of resected SPS detected advanced sclerosis of all the layers of the
      ureteral and renal pelvis walls in chronic mucosal inflammation. The operative
      technique is described. Postoperative complications were absent. The control
      examination upon discharge and 1-15 year follow-up results registered good
      functioning of the operated-on kidney with rehabilitation of the calyceal-pelvic
      structure. Plastic operation was successful due to creation of a wide anastomosis
      between the resected renal pelvis and the ureter with obligatory renal drainage
      using nephrostoma. In other 4 cases of SPS strictures graft plastic operations
      were made. Good functional results were achieved in 3 patients. The long-term
      results favour resections and creation of pelviureteral anastomosis by Kuchere.

PMID- 15989020
TI  - [The role of phytotherapy in pre- and postoperative period in patients with
      urolithiasis].
AB  - Effects of a biologically active food additive Prolit (PT Industry Djamu
      Borobudur, Indonesia) on the urinary system and metabolic status of patients with
      urolithiasis were studied. Total urinalysis, biochemical blood and urine tests by
      12 indices, ultrasonic investigation of the kidneys, excretory and plain
      urography were made in 30 patients aged 23 to 70 years (7 females, 23 males).
      Prolit was given in a dose 1125 mg three times a day for 1-6 months. Prolit
      decreased hypercalciuria and urinary pH. A trend was observed to lowering of the
      degree of leukocyturia, hyperuricemia, hyperuria and hyperoxaluria. Urolithiasis
      recurrences were absent in 10 cases of 12 (83%), in 18 of 20 patients (90%)
      concrements did not increase in size. Prolit had no side effects.

PMID- 15989021
TI  - [Spontaneous ruptures of renal tumors].
AB  - Spontaneous retroperitoneal hemorrhages are a rare but severe complication of
      retroperitoneal organs and tissues disorders. For the last five years we treated
      10 patients (7 females and 3 males) with spontaneous subcapsular or paranephral
      hematoma resultant from renal tumor rupture. Morphologically, 4 tumors were renal
      angiomyolipoma and 6 tumors--renal cell carcinoma. Most characteristic symptoms
      consisted in acute lumbar pain on the affected side (100%) and the absence of
      macrohematuria in all the patients. Marked hemodynamic disorders of a hypotonic
      type were observed in 50% patients (4 patients lost consciousness). Left kidney
      tumor ruptures were more frequent (70%). An accurate preoperative diagnosis was
      made in 70% cases with application of ultrasonic investigation, computed
      tomography, MR imaging, Of 4 patients with renal angiomyolipoma, conservative
      surgery (enucleation, enucleoresection) was conducted in 3 (75%) patients. Of 6
      patients with renal cell carcinoma, tumor removal with preservation of the kidney
      was feasible only in 1 (16.6%) patient, in the rest 5 patients radical
      nephrectomy was made. In 2 patients it was combined with venacavathrombectomy.
      Thus, patients with spontaneous rupture of renal tumors are characterized by
      absence of macrohematuria, prevalent location of the tumor on the left and in the
      middle segment of the kidney (90%), high diagnostic effectiveness of
      ultrasonography, no rise in local tumor recurrence consequently to rupture of the
      tumor tissue.

PMID- 15989022
TI  - [Intestinal plastic surgery of the ureter].
AB  - Intestinal plastic surgery for ureteral stricture was made in 25 patients (10
      unilateral and 15 bilateral strictures). Stricture of the lower third of both
      ureters was primarily second to operations for colorectal cancer, urinary bladder
      diverticulesis and scars after radiotherapy. Unilateral strictures resulted from
      postradiation changes in 9 patients and a shotgun wound of the ureter in 1
      patient. Grafts of an isolated segment of the ileum and the vermiform process on
      the mesentery were transplanted in 22 and 3 patients, respectively. Postoperative
      intestinal ileus was observed only in one patient who was treated with
      relaparotomy, intestinal intubation and abdominal drainage. Another patient was
      reoperated for failure of ureteroappendicoanastomosis. The results of the
      reoperations were successful. No lethal outcomes were recorded. Upon 0.5-7 year
      follow-up, all the patients restored normal urodynamics and function of the
      affected kidney. Thus, use of an isolated segment of the small intestine ensures
      repair of the defects of one or both the ureters of any location and length.
      Intestinal repair in extended ureteral lesion is an operation of choice as it
      reestablishes urine outflow from the kidney, improves its function, relieves
      symptoms of chronic pyelonephritis and puts away continuous renal and ureteral
      fistulas.

PMID- 15989023
TI  - [Autotransplantation of the kidney in ureteral injuries].
AB  - In 1988-2003 we operated 156 patients with various ureteral lesions. Of them 7
      patients (6 males and 1 female, mean age 34-43 years) received kidney transplant
      (autotransplantation). Ureteral lesions were caused by previous surgery (n=3),
      gunshot wound (n=2), urolithiasis (n=2. The follow-up results (for 15 period
      maximum) show that operative outcomes were satisfactory in 6 patients. One
      transplant was removed 7 days after the transplantation because of purulent
      pyelonephritis and necrosis of the ureter. The rest patients retain good function
      of the transplanted kidney and passability of the upper urinary tract. Thus,
      surgical autotransplantation of the kidney performed in affected middle and low
      thirds of the ureter is an alternative to life-long nephrostomy and nephrectomy
      and has a good long-term prognosis in relation to function of a transplanted
      kidney.

PMID- 15989024
TI  - [Renal function after cystectomy and intestinal plastic surgery in cancer of the
      urinary bladder].
AB  - We studied renal function after intestinal plastic reconstruction of the urinary
      bladder with an ilial graft in 52 patients with urinary bladder cancer (UBC). We
      created artificial urinary bladder in 39 patients and urinary reservoir in 13
      ones. The control group consisted of 40 patients who had undergone Brikker's
      operation (n=13) or ureterocutaneostomy (n=27). Most information about renal
      function was obtained with dynamic nephroscintigraphy and color duplex scanning
      of renal vessels. As shown by 5-year postoperative follow-up, late postoperative
      condition of the kidneys is determined by the method of urine derivation. Ilial
      plastic reconstruction of the urinary bladder has a minimal negative effect on
      renal function while quality of life improves. Ureterocutaneostomy deteriorates
      renal function, the same in Brikker's operation but in a lesser degree. Thus,
      ilial plastic repair of the urinary bladder is a method of choice in the
      treatment of patients with invasive cancer of the urinary bladder.

PMID- 15989025
TI  - [Endoscopic operations in invasive cancer of the urinary bladder].
AB  - Long-term results of conservative treatment of 153 patients with invasive cancer
      of the urinary bladder were studied retrospectively. The patients had stage T2
      (n=121, 79.1%), T3 (n=26, 17%), T4 (n=6, 3.9%). All the patients had transitional
      cell cancer. GI, G2 and G3 tumors were registered in 104 (68%), 35 (24%) and 12
      (8%) cases, respectively. 88 (57.5%) patients received combined treatment, 65
      (42.5%) patients--only surgery. In the patients with a small invasive tumor of
      the urinary bladder subjected to surgery alone (TUR-vaporization), overall 5-year
      survival was 70.4%. In patients with advanced cancer of the urinary bladder who
      had received curative radiotherapy in case of superficial residual tumor had TUR
      vaporization of the urinary bladder overall 5-year survival was 76.5%. In
      patients exposed to large-fraction (TFD 20-25 Gy) preoperative radiotherapy
      followed by TUR-vaporization, survival at this moment was 84.6%. Three-year
      overall and recurrence-free survival at stage T2 was 97.5 and 47.4%,
      respectively; at stage T3 and T4 overall 3-year survival was 57.1 and 26.6%,
      respectively. Thus, the conclusion is that transurethral electrosurgery in
      conservative therapy of patients with invasive cancer of the urinary bladder is a
      promising approach.

PMID- 15989026
TI  - [Complications of transrectal biopsy of the prostate].
AB  - The aim of the study was to assess frequency of various complications of
      transrectal multifocal biopsy of the prostate (TMBP), to specify prophylactic
      measures against such complications. Primary TMBP under US guidance was made in
      612 patients (mean age 65.8 years, mean level of PSA 12.6 ng/ml). TMBP
      complications include: hematuria (220 patients, 35.9%), hemospermia (166
      patients, 27.1%), pain in the perineum and the rectum (189, 30.9%), acute
      prostatitis (21 patients, 3.4%), acute orchiepididymitis (7 patients, 1.1%),
      acute urine retention (9 patients, 1.5%), long-term rectal hemorrhage (13
      patients, 2.1%), loss of consciousness during the biopsy (7 patients, 1.1%). The
      analysis of TMBP complications leads to the conclusion that adequate preparation
      of the patients and accurate conduction of the prostatic biopsy technique under
      US guidance make this invasive manipulation diagnostically effective and safe.

PMID- 15989027
TI  - [Validity of using physical therapy in combined treatment of chronic
      prostatitis].
AB  - To evaluate efficacy of combined physiotherapy in patients with chronic
      prostatitis (chronic bacterial, chronic abacterial prostatitis), an open
      comparative trial was made by specialists of the Research Institute of Urology in
      2003-2004 of the unit Andro-Gin. Before the treatment, a standard examination was
      made including analysis of case history and complaints, rectal palpation,
      questionnaire filling-in, prostatic secretion tests, PCR diagnosis, transrectal
      ultrasonic scanning and uroflowmetry. In group 1 (chronic bacterial prostatitis)
      given monotherapy with an etiotropic drug (ED) or combination of ED with Andro
      Gin treatment, a significant improvement was achieved by the scale NIH-CPSI,
      Sorensen scale (p < 0.05). In group 2 (chronic abacterial prostatitis with
      inflammation) subgroups C,D,E patients showed significant improvement by the
      scales NIH-CPSI and Sorensen (p < 0.05). The highest symptomatic effect was
      recorded in the subgroup D in combined treatment with ED and Andro-Gin
      physiotherapy. In group 3 low NIH-CPSI scale score occurred due to alleviation of
      pain in subgroup F (p < 0.05), In subgroup G symptoms by the above scales did not
      change. Uroflowmetry featured moderate dynamics of the increment in maximal
      voiding speed. Voiding improved significantly in subgroup F in patients with
      chronic abacterial prostatitis in the absence of inflammation.

PMID- 15989028
TI  - [Using energetic Doppler-angiography in combined diagnostics of prostatic
      abscess].
AB  - Diagnostic possibilities of conventional clinical-laboratory, physical methods,
      seroscale echography and energetic dopplerangiography (EDA) were compared in 32
      patients with prostatic abscess (PA). Nonspecific symptoms hamper conventional PA
      diagnosis. PA is detected, as a rule, at transrectal ultrasonic investigation
      (TUI) which is effective in formed PA (sensitivity 100%) but is low effective in
      early PA (sensitivity 50%). Minimal size of PA detectable by TUI is 7 mm (mean 12
      +/- 1.2 mm). EDA improves diagnostic potential of TUI in infiltrative PA
      (sensitivity 91.7%). In established PA, EDA confirms TUI findings. Transabdominal
      ultrasonography has insufficient resolution and must be used for PA screening.

PMID- 15989029
TI  - [Clinical efficacy and safety of terazosine (setegis) in patients with benign
      prostatic hyperplasia with concomitant cardiovascular diseases].
AB  - The aim of the study was assessment of clinical efficacy and safety of terazosine
      (setegis) in patients with benign prostatic hyperplasia (BPH) and concomitant
      cardiovascular disease. A total of 62 BPH patients with cardiovascular disease
      (ischemic heart disease, hypertension) having indications for alpha
      adrenoblockers (mean age 74 +/- 11 years, 58-85) received terazosine in a dose 1
      5 mg for 2 months. Clinical efficacy of terazosine was assessed by IPSS scale,
      residual urine, maximal voiding velocity. Safety of the drug was controlled by
      monitoring of arterial pressure, ECG, echo-CG. All the tests were made before
      therapy, on the treatment week 2, 4 and 8. The response was 90.3%. Overall
      symptoms score decreased by 37.0%, quality of life score rose by 23.8%. Amount of
      residual urine fell by 64.8%, maximal voiding velocity increased by 36.6%.
      Moderate effects of the drug (vertigo, weakness) occurred in 11.3% patients for 1
      or 2 days after start of the therapy and were due to a moderate fall of arterial
      pressure in normotensive patients. Later artertial pressure stabilized, ECG
      registered no exacerbations of ischemic heart disease, no anginal attacks, no
      change in cardiac rhythm. Thus, terazosine (setegis) is effective and safe in BPH
      patients with cardiovascular disease. Pretreatment consultation of the
      cardiologist is desirable for correction of basic antianginal therapy.

PMID- 15989030
TI  - [Systemic approach to investigation of levitra efficacy in patients with chronic
      prostatitis with erectile dysfunction].
AB  - Ultrasonic dopplerography of prostatic, scrotal and penile vessels before and
      after intake of levitra in a dose 10 mg was made in 22 patients with chronic
      abacterial prostatitis in combination with erectile dysfunction and after their
      combined levitra treatment for a month taken each other day. It was found that
      levitra accelerates arterial inflow to the prostatic gland, testicles and penis
      (even in the absence of sexual stimulation and erection). This evidence indicates
      a distinct vasculogenic effect of levitra on male genitalia. Thus, levitra is a
      promising drug in the treatment of chronic prostatitis, excretory infertility. It
      is recommended to take levitra regularly 2-3 times a week to manage vascular
      genital disorders.

PMID- 15989031
TI  - [Urodynamics of the lower urinary tract of the fetus during physiological
      pregnancy].
AB  - To evaluate urodynamic parameters of the fetal lower urinary tracts in
      physiological pregnancy and without malformations, a monitoring of filling and
      voiding of fetal urinary bladder was made by the results of ultrasonic study of
      76 fetuses at getation term 20-40 weeks. All the infants of the first year of
      life have undergone clinical examination of urination, 24-h monitoring of
      spontaneous voiding rhythms, ultrasonic measurements of residual urine. Normal
      urodynamic parameters of fetal lower urinary tract depending on gestation
      duration were obtained. These parameters can be used as prognostic criteria in
      diagnosis of intrauterine urinary disorders.

PMID- 15989032
TI  - [Analysis of protein concentration in the urine of children with metabolic
      nephropathy, crystal-calcium crystalluria].
AB  - We compared the efficacy of a routine sulphosalycilic acid method and a new
      technique of pirogallolic red staining for urine protein assay in children with
      metabolic nephropathy, crystal-calcium crystaluria. The former method was found
      ineffective in proteinuria diagnosis in children with metabolic nephropathy. The
      pirogallolic method appeared more effective as it detects microproteinuria and
      therefore allows accurate diagnosis, control of its treatment and finally to
      improve the results of therapeutic and prophylactic measures.

PMID- 15989033
TI  - [Extracorporeal lithotripsy of ureteral calculi after cystectomy with
      ureterosygmoanastomosis in progressive bladder cancer].

PMID- 15989034
TI  - [Symposium "Nephropathy Caused by Contrast Media" (in the program of the XLI
      congress of the European Kidney Association. 15-18 May, 2004, Lisbon)].

PMID- 15989035
TI  - [Transurethral prostatic resection in the treatment of patients with prostatic
      cancer].

PMID- 15989036
TI  - [The role of urogenital infections in etiology of cystitis and non-obstructive
      pyelonephritis in women (part 1)].

PMID- 15989037
TI  - Improved algorithm for simulations of divergent-light halos.
AB  - Divergent-light halos are produced when light from nearby light sources is
      scattered by ice crystals in the atmosphere. We present a theory of divergent
      light halos leading to an improved algorithm for the simulation of such halos.
      Contrary to the algorithm that we presented earlier for simulating such halos,
      the new algorithm includes a mathematically rigorous weighting of the events. The
      computer implementation is very compact, and the whole procedure is elegant and
      conceptually easy to understand. We also present a new simulation atlas showing
      halos produced by crystals of different shapes and orientations for a set of
      elevations of the light source.

PMID- 15989038
TI  - Extracting mode components in laser intensity distribution by independent
      component analysis.
AB  - With increasingly sophisticated laser applications in industry and science, a
      reliable method to characterize the intensity distribution of the laser beam has
      become a more and more important task. However, traditional optic and electronic
      methods can offer only a laser beam intensity profile but, cannot separate the
      main mode components in the laser beam intensity distribution. Recently,
      independent component analysis has been a surging and developing method in which
      the goal is to find a linear representation of a non-Gaussian data set. Such a
      linear representation seems to be able to capture the essential structure of a
      laser beam profile. After assembling image data of a laser spot, we propose a new
      analytical approach to extract laser beam mode components based on the
      independent component analysis technique. For noise reduction and laser spot area
      location, wavelet thresholding, Canny edge detection, and the Hough transform are
      also used in this method before extracting mode components. Finally, the
      experimental results show that our approach can separate the principal mode
      components in a real laser beam efficiently.

PMID- 15989039
TI  - Temporal evolution of the laser-induced breakdown spectroscopy spectrum of
      aluminum metal in different bath gases.
AB  - The spectral emission of gas-phase aluminum and aluminum oxide was measured
      during and immediately after exposure of a bulk-aluminum sample to a laser
      induced spark produced by a focused, pulsed laser beam (Nd:YAG, 10-ns pulse
      duration, 35 mJ/pulse, lambda = 1064 nm). The spectral emission was measured as a
      function of time after the onset of the laser pulse, and it was also measured in
      different bath gases (air, nitrogen, oxygen, and helium).

PMID- 15989040
TI  - Laser-induced carbon plasma emission spectroscopic measurements on solid targets
      and in gas-phase optical breakdown.
AB  - We report measurements of time- and spatially averaged spontaneous-emission
      spectra following laser-induced breakdown on a solid graphite/ambient gas
      interface and on solid graphite in vacuum, and also emission spectra from gas
      phase optical breakdown in allene C3H4 and helium, and in CO2 and helium
      mixtures. These emission spectra were dominated by CII (singly ionized carbon),
      CIII (doubly ionized carbon), hydrogen Balmer beta (Hbeta), and Swan C2 band
      features. Using the local thermodynamic equilibrium and thin plasma assumptions,
      we derived electron number density and electron temperature estimates. The former
      was in the 10(16) cm(-3) range, while the latter was found to be near 20000 K. In
      addition, the vibration-rotation temperature of the Swan bands of the C2 radical
      was determined to be between 4500 and 7000 K, using an exact theoretical model
      for simulating diatomic emission spectra. This temperature range is probably
      caused by the spatial inhomogeneity of the laser-induced plasma plume.
      Differences are pointed out in the role of ambient CO2 in a solid graphite target
      and in gas-phase breakdown plasma.

PMID- 15989041
TI  - Glass-batch composition monitoring by laser-induced breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy is an almost ideal technique for the in situ
      monitoring of the composition of a glass batch before it enters the glass-melting
      furnace, saving a significant amount of energy by the optimization of the furnace
      parameters for a particular composition of the glass batch. We investigate this
      application of laser-induced breakdown spectroscopy by determining the elemental
      composition of the glass batch used (i) as a surrogate for radioactive glass
      waste and (ii) to manufacture the most common type of flat glass. The surrogate
      glass-batch and flat-glass calibration curves for the major constituents have
      been prepared using both the line intensity and the line-intensity ratio. The
      analytical figure of merit of the glass-batch data obtained from the two
      different detection systems, namely, the Czerny-Turner spectrometer with an
      intensified diode-array detector and the echelle spectrometer fitted with an
      intensified CCD camera, are compared.

PMID- 15989042
TI  - Wide-bandwidth mode-hop-free tuning of extended-cavity GaN diode lasers.
AB  - We present a new approach for extended-cavity diode-laser tuning to achieve wide
      mode-hop-free tuning ranges. By using a multiple piezoactuated grating mount, the
      cavity length and grating angle in the laser can be adjusted independently,
      allowing mode-hop-free tuning without the need for a mechanically optimized pivot
      point mount. Furthermore, synchronized diode injection-current tuning allows
      diode lasers without antireflection coatings to be employed. In combination these
      two techniques make the construction of a cheap, efficient, and easily optimized
      extended-cavity diode laser possible. A theoretical analysis is presented for
      optimal control of piezoactuator displacements and injection current to achieve
      the widest possible mode-hop-free tuning ranges, and a comparison is made with
      measurements. The scheme is demonstrated for blue and violet GaN lasers operating
      at approximately 450 nm and approximately 410 nm, for which continuous tuning
      ranges exceeding 90 GHz have been achieved. Examples of applications of these
      lasers are also given.

PMID- 15989043
TI  - Diatomic Honl-London factor computer program.
AB  - A new method is presented for computation of diatomic rotational line strengths,
      or Honl-London factors. The traditional approach includes separately calculating
      line positions and Honl-London factors and assigning parity labels. The present
      approach shows that one merely computes the line strength for all possible term
      differences and discards those differences for which the strength vanishes.
      Numerical diagonalization of the upper and lower Hamiltonians is used, which
      directly obtains the line positions, Honl-London factors, total parities, and e/f
      parities for both heteronuclear and homonuclear diatomic molecules. The FORTRAN
      computer program discussed is also applicable for calculating n-photon diatomic
      spectra.

PMID- 15989044
TI  - Fiber-optic sensor for handgrip-strength monitoring: conception and design.
AB  - Handgrip strength is an easy measure of skeletal muscle function as well as a
      powerful predictor of disability, morbidity, and mortality. In order to measure
      grip strength, a novel fiber-optic approach is proposed and demonstrated. The
      strain-dependent wavelength response of fiber Bragg gratings has been utilized to
      obtain the strength of individual fingers. Finite-element analysis is carried out
      to optimize the pressure transmission from the finger to the fiber Bragg grating.
      The effect of stiffness of the pressurizing media, its thickness, and the effect
      of contact fraction are evaluated. It is found that significant enhancement in
      the pressure sensitivity and wavelength-tuning range is achievable by optimizing
      these parameters. Also the stress-induced birefringence could be reduced to an
      insignificant near-zero value. The device is calibrated in terms of load to
      convert the wavelength shift to the strength of the grip. The time-dependent
      wavelength fluctuation is also studied and presented.

PMID- 15989045
TI  - Superresolution with nonorthogonal polarization coding.
AB  - One can achieve high-resolution (superresolution) imaging, beyond the classical
      limit, by exploiting certain degrees of freedom such as time and polarization for
      the object under consideration. We present an implementation, based on
      polarization coding, that requires insertion of a single mask into the object
      plane followed by postprocessing of the detected signal. We describe the
      procedure and provide experimental evidence for the implementation of the
      proposed technique.

PMID- 15989046
TI  - Brewster angle with a negative-index material.
AB  - The demonstration and confirmation of metamaterials with simultaneous negative
      permittivity and permeability, and thus a negative refractive index, has resulted
      in a surge of interest in the reflection and refraction phenomena at the
      interfaces of these so-called negative-index materials (NIMs). We present a
      systematic study of the Brewster angle, i.e., the angle of incidence at which no
      reflection occurs, for both TE and TM waves scattering at the interface between
      two semi-infinite planar media, one of which may be a NIM. Detailed physical
      explanations that account for the Brewster angle for a plane wave incident upon a
      NIM are provided under the framework of the Ewald-Oseen extinction theorem,
      considering the reemission of induced electric and magnetic dipoles. The
      conditions under which the Brewster angle exists are concisely summarized in a
      map of different material parameter regimes.

PMID- 15989047
TI  - Distinction of cervical cancer biopsies by use of infrared microspectroscopy and
      probabilistic neural networks.
AB  - Fourier-transform infrared spectroscopy has shown alterations of spectral
      characteristics of cells and tissues as a result of carcinogenesis. The research
      reported here focuses on the diagnosis of cancer in formalin-fixed biopsied
      tissue for which immunochemistry is not possible and when PAP-smear results are
      to be confirmed. The data from two groups of patients (a control group and a
      group of patients diagnosed with cervical cancer) were analyzed. It was found
      that the glucose/phosphate ratio decreases (by 23-49%) and the RNA/DNA ratio
      increases (by 38-150%) in carcinogenic compared with normal tissue. Fourier
      transform microspectroscopy was used to examine these tissues. This type of study
      in larger populations may help to set standards or classes with which to use
      treated biopsied tissue to predict the possibility of cancer. Probabilistic
      neural networks and statistical tests as parts of these biopsies predict the
      possibility of cancer with a high degree of accuracy (> 95%).

PMID- 15989048
TI  - Computations of the acoustically induced phase shifts of optical paths in
      acoustophotonic imaging with photorefractive-based detection.
AB  - Acoustophotonic imaging uses ultrasound-modulated scattered light to improve the
      quality of optical imaging in diffusive media. Experiments that use
      photorefractive-crystal-based detection have shown that there is a large dc shift
      in the acoustically modulated or ac optical signal, which could be utilized to
      further improve optical imaging resolution. We report that photon paths in a
      diffusive medium were generated by a Monte Carlo simulation, and the optical
      phase shifts of the various photons induced by the presence of a realistic
      focused ultrasound beam were calculated. Quantities that characterize the ac and
      dc signal components were evaluated by use of the calculated phase shifts. It was
      confirmed that the dc component dominates owing to coherent summation of the
      contributions from all the photons.

PMID- 15989049
TI  - Micro gradient-index conical lenses: simulation and fabrication methods.
AB  - In this paper, a micro gradient-index conical lens, which has a larger acceptance
      angle than a conventional microlens, is presented. Methods on how to simulate
      these lenses in commercial optical design software CodeV are introduced, and the
      effects of several index profiles and cone shapes are compared in simulation.
      Results show that a micro gradient-index conical lens has a four times larger
      acceptance angle compared with a microlens. Additionally, conical lenses with a
      Gaussian-index profile show a larger acceptance angle than those with a solid
      refractive index. Fabricated conical lenses show an acceptance angle of more than
      27 degrees for a detection threshold of 50%, which agrees with the simulation
      result.

PMID- 15989050
TI  - Control of spatial polarization by use of a liquid crystal with an optically
      treated alignment layer and its application to beam apodization.
AB  - We have investigated the alignment of a liquid crystal whose orientation is
      controlled by photoisomerization reaction for use in developing optical devices
      to improve beam quality. A glass window of a liquid-crystal cell that is coated
      with poly(vinyl alcohol) doped with azo dye was illuminated with a Hg lamp. We
      confirmed the dependence of the spatially controlled alignment direction of a
      liquid crystal on the irradiation time of this ultraviolet light. The new azo dye
      used in this study substantially reduced the illumination energy density required
      for aligning liquid-crystal molecules. We have demonstrated the control of
      polarization and successfully fabricated a serrated apodizing aperture and a soft
      aperture.

PMID- 15989051
TI  - Light propagation through a monolayer of discrete scatterers: analysis of
      coherent transmission and reflection coefficients.
AB  - An investigation of the coherent transmission and reflection coefficients of a
      monolayer of spherical scatterers as a function of their size, optical constants,
      and concentration is carried out. An analysis is performed of the quasi
      crystalline approximation of the multiple-wave scattering theory and on the
      single-scattering approximation (SSA). The results permit determining the limits
      of applicability of the SSA to the layers with the partial ordering of spherical
      scatterers in analyzing the phases of the transmitted and the reflected waves.
      The phase of the transmitted and the reflected waves is investigated in the
      conditions of the quenching effect. It is shown that in such a case small changes
      in the refractive index of particles can cause dramatic phase changes. This
      effect can be used to modulate the light-wave phase, e.g., by electrically
      controlled composite liquid-crystals films.

PMID- 15989052
TI  - Multilayer optical thin films for use at terahertz frequencies: method of
      fabrication.
AB  - A new method of fabricating multilayer optical coatings used at terahertz
      frequencies has been developed. Using plasma-enhanced chemical-vapor deposition,
      a multilayer antireflection coating for germanium optics at terahertz frequencies
      was fabricated. The coating consists of amorphous silicon and silicon-oxide
      layers. The transmittance and structure of the coating were experimentally
      investigated. The transmittance spectrum of the coating on the Ge substrate shows
      a wideband antireflection behavior in the 40-120 cm(-1) region.

PMID- 15989053
TI  - Fourier analysis of harmonic frequency transmission dielectric structures.
AB  - We use an analytical calculation based on the Fourier-transform method to study
      the transmission spectra of multilayer dielectric optical structures as a
      function of the relative widths of the layers that constitute the unit cell. We
      can select which harmonics of the fundamental design frequency are transmitted.
      The results of this Fourier-transform approach are compared with the exact
      transmission calculated by means of the transfer matrix method and provide a more
      intuitive understanding of the transmission spectrum. A simple phasor diagram is
      derived from this Fourier-transform analysis for this purpose. Inasmuch as it is
      difficult for us to perform experiments in the optical region, we fabricate rf
      analogs of these structures, using coaxial cables that have different impedances.
      Experimental results agree with theory.

PMID- 15989054
TI  - Face recognition by using feature-specific imaging.
AB  - We present a face-recognition system based on the optical measurement of linear
      features. We describe a polarization-based optical system that computes linear
      projections of an incident irradiance distribution. We quantify the fundamental
      limitations of optical feature measurement. We find that higher feature fidelity
      can be obtained by feature-specific imaging than by postprocessing a conventional
      image. We present feature-fidelity results for wavelet, principal component, and
      Fisher features. We study face recognition by using a k-nearest neighbors
      classifier and two different feed-forward neural networks. Each image block is
      reduced to either a one- or a two-dimensional feature space for input to these
      recognition algorithms. As high as 99% recognition has been achieved with one
      dimensional wavelet feature projections and 100% has been achieved with two
      dimensional projections. A 95-fold increase in noise tolerance by use of feature
      specific imaging has been demonstrated for an example of the face-recognition
      problem. An optical experiment is performed to validate these results.

PMID- 15989055
TI  - Empirical relationships between extinction coefficient and visibility in fog.
AB  - Relationships between visibility and an extinction coefficient that is due to fog
      in optical windows that are free from molecular absorption are derived. The
      extinction coefficients in the visible (0.55 microm), the near IR (1.2 microm),
      and the mid IR (3.7 microm) are comparable to and roughly twice as much as that
      in the far IR (10.6 microm) when visibility is less than a few hundred meters.
      The advantage of far-IR radiation compared with shorter wavelengths grows as
      visibility exceeds 500 m. Correspondingly, the relationship between extinction
      coefficient and visibility becomes more sensitive to variations in the particle
      size distribution of fog.

PMID- 15989056
TI  - Analysis of shipboard aerosol optical thickness measurements from multiple
      sunphotometers aboard the R/V Ronald H. Brown during the Aerosol Characterization
      Experiment--Asia.
AB  - Marine sunphotometer measurements collected aboard the R/V Ronald H. Brown during
      the Aerosol Characterization Experiment-Asia (ACE-Asia) are used to evaluate the
      ability of complementary instrumentation to obtain the best possible estimates of
      aerosol optical thickness and Angstrom exponent from ships at sea. A wide range
      of aerosol conditions, including clean maritime conditions and highly polluted
      coastal environments, were encountered during the ACE-Asia cruise. The results of
      this study suggest that shipboard hand-held sunphotometers and fast-rotating
      shadow-band radiometers (FRSRs) yield similar measurements and uncertainties if
      proper measurement protocols are used and if the instruments are properly
      calibrated. The automated FRSR has significantly better temporal resolution (2
      min) than the hand-held sunphotometers when standard measurement protocols are
      used, so it more faithfully represents the variability of the local aerosol
      structure in polluted regions. Conversely, results suggest that the hand-held
      sunphotometers may perform better in clean, maritime air masses for unknown
      reasons. Results also show that the statistical distribution of the Angstrom
      exponent measurements is different when the distributions from hand-held
      sunphotometers are compared with those from the FRSR and that the differences may
      arise from a combination of factors.

PMID- 15989057
TI  - Intensity-referenced and temperature-independent curvature-sensing concept based
      on chirped fiber Bragg gratings.
AB  - An intensity-referenced temperature-independent curvature-measurement technique
      that uses a smart composite that comprises two chirped fiber Bragg gratings is
      demonstrated. The two gratings are embedded on opposite sides of the composite
      laminate and act simultaneously as curvature sensors and as wavelength
      discriminators, enabling a temperature-independent intensity-based scheme to
      measure radius of curvature. Also, the system's performance is independent of
      arbitrary power losses that are induced in the lead fibers to the sensing head.
      It is demonstrated that the measurement range depends on the relative positions
      of the chirped fiber Bragg gratings and on their spectral bandwidths. By using
      two chirped fiber Bragg gratings with bandwidths W1 = 2.8 nm and W2 = 3.7 nm and
      with central wavelengths at lambda 01 = 1560.3 nm and lambda 02 = 1563.7 nm, we
      obtained a resolution of 1.6 mm/square root of Hz for the measurement of the
      radius of curvature (approximately R = 350 mm) over the measurement range 190 mm
      < R < infinity.

PMID- 15989058
TI  - Improvement in visibility of an in-focus reconstructed image in digital
      holography by reduction of the influence of out-of-focus objects.
AB  - When a reconstruction is performed on a digital holographic image that contains
      small objects at different depths, diffraction that is due to out-of-focus
      objects disrupts the visibility of the nearby focused objects. We propose a
      method to substitute for focused object amplitudes other amplitudes that will
      reduce propagation diffraction effects when other depths are investigated. The
      replacement amplitudes are computed by use of an algorithm that reduces the
      highest spatial frequencies of the resultant image. The theoretical aspects of
      the method are presented, and results for simulated and experimental examples are
      shown.

PMID- 15989059
TI  - Linear optoacoustic underwater communication.
AB  - The linear mechanism for optical-to-acoustic energy conversion is explored for
      optoacoustic communication from an in-air platform or surface vessel to a
      submerged vessel such as a submarine or unmanned undersea vehicle. The
      communication range that can be achieved is addressed. A number of conventional
      signals used in underwater acoustic telemetry applications are shown to be
      capable of being generated experimentally through the linear optoacoustic regime
      conversion process. These results are in agreement with simulation based on
      current theoretical models. A number of practical issues concerning linear
      optoacoustic communication are addressed that lead to a formulation of a linear
      regime optoacoustic communication scheme. The use of oblique laser beam incidence
      at the air-water interface to obtain considerable in-air range from the laser
      source to the in-water receiver is addressed. Also, the effect of oblique
      incidence on in-water range is examined. Next, the optimum and suboptimum linear
      optoacoustic sound-generation techniques for selecting the optical wavelength and
      signaling frequency for optimizing in-water range are addressed and discussed.
      Optoacoustic communication techniques employing M-ary frequency shift keying and
      multifrequency shift keying are then compared with regard to communication
      parameters such as bandwidth, data rate, range coverage, and number of lasers
      employed.

PMID- 15989060
TI  - Comparison between orthogonal subspace projection and background subtraction
      techniques applied to remote-sensing data.
AB  - The basic measurement equation r = B + alphad + n is solved for alpha (the weight
      or abundance of the spectral target vector d) by two methods: (a) by subtracting
      the stochastic spectral background vector B from the spectral measurement's
      vector r (subtraction solution) and (b) by orthogonal subspace projection (OSP)
      of the measurements to a subspace orthogonal to B (the OSP solution). The
      different geometry of the two solutions and in particular the geometry of the
      noise vector n is explored. The angular distribution of the noise angle between B
      and n is the key factor for determining and predicting which solution is better.
      When the noise-angle distribution is uniform, the subtraction solution is always
      superior regardless of the orientation of the spectral target vector d. When the
      noise is more concentrated in the direction orthogonal to B, the OSP solution
      becomes better (as expected). Simulations and one-dimensional hyperspectral
      measurements of vapor concentration in the presence of background radiation and
      noise are given to illustrate these two solutions.

PMID- 15989061
TI  - [Advances in molecular nutrition: nutrigenomics and/or nutrigenetics].
AB  - The application of molecular biology techniques and the success of the Human
      Genome Project have opened a new era for both Medicine and Nutrition. To date, at
      least 1,000 human genes causing disease have been identified and partially
      characterized, 97% of which we now know that are the cause of monogenic diseases.
      However, other diseases such as obesity, cardiovascular disease, diabetes, and
      cancer are due to complex interactions between several genes and environmental
      factors. In spite of the many association studies, over 600 published since 2002,
      the molecular base of chronic diseases is still uncertain. Information about
      nucleotide polymorphisms and haplotypes maps is an additional resource for
      identifying genes implicated in diseases. Genomic development gets close, however
      we frequently do not accurately know the dietary components and their mechanisms
      that importantly influence on genetic information expression and its pathologic
      impairments. The food industry has the opportunity for utilizing the bioactive
      components of foods to improve health and prevent diseases while considering the
      consumers' genetic constitution. This new era of molecular nutrition--gene
      nutrient interactions--may evolve in several ways, although two of them are
      essential. On the one hand, the study of the influence of nutrients on gene
      expression (nutrigenomics) and, on the other hand, to know the influence of
      genetic variations in the organism response to nutrients (nutrigenetics).

PMID- 15989062
TI  - Nutritional risks and colorectal cancer in a Portuguese population.
AB  - BACKGROUND: Food and nutrition as major causes of colorectal cancer (CRC) are
      still debatable. AIM OF THE STUDY: This cross-sectional study in a Portuguese
      population aimed to characterize and identify "high-risk" diets/life-styles and
      explore their associations with colorectal cancer. METHODS: In 70 colorectal
      cancer patients and 70 sex, age-matched subjects without cancer history, we
      evaluated: diet history and detailed nutrient intake (DIET-PLAN5 2002, UK),
      alcohol (amount, type, years), smoking (number packages/year, years), physical
      activity, co-morbidities and body mass index. Age-adjusted Relative Risks were
      calculated, Proportional Hazards models adjusted the analysis for multiple risk
      factors. RESULTS: Smoking was a risk factor (1.90). Increased colorectal cancer
      risk regarding the lowest vs the highest intake quartile emerged for: vitamin B12
      (3.41), cholesterol (3.15), total fat (2.87), saturated fat (1.98), animal
      protein (1.95), energy (1.85), alcohol (1.70), iron (1.49), refined carbohydrates
      (1.39). Reduced colorectal cancer risk for the highest vs the lowest intake
      quartile was found for: n-3 fatty acids (0.10), insoluble fiber/folate (0.15),
      flavonoids/vitamin E (0.25), isoflavones/beta-carotene (0.30), selenium (0.36),
      copper (0.41), vitamin B6 (0.46). CONCLUSION: Our results corroborated well
      established risk factors and identified emergent nutrients. Prolonged excessive
      intake of macronutrients and some micronutrients concurrent with marked deficits
      of fiber and protective compounds were dominant in colorectal cancer and more
      significant than alcohol and smoking. The interaction diet-colorectal cancer is
      consistent and the relevance of new nutrients is emerging.

PMID- 15989063
TI  - [Implementation of an assisted electronic prescription system applied to
      parenteral nutrition in a general hospital].
AB  - Integrated and shared information systems allow obtaining a high degree of
      information about processes, costs and outcomes, and considerably reducing
      prescription errors. Assisted electronic prescription, in the setting of total
      parenteral nutrition, integrated with other hospital databases and with the
      hospital drugs management system, is a tool that allows increasing patient'
      safety (by reducing prescription errors), improving quality assistance, improving
      information systems and information management and the efficiency of used
      resources. In this work, implementation of an assisted electronic prescription
      system applied to parenteral nutrition in a hospital and processes reengineering
      performed in the nutrition setting are described. This implementation was
      performed by medical staff from the Nutrition and Diet Department and pharmacists
      from the Pharmacy Department of Ramon y Cajal Hospital using "Nutriwin" computer
      software. For two months prior and after its implementation, a follow-up of time
      consumed in the circuit prescription-validation-elaboration-dispensation of
      parenteral nutrition formulas has been performed. After implementation, treatment
      orders reach on average 1 h and 15 minutes sooner the Pharmacy Department; by
      avoiding transcription, a saving of 3 min per nutrition formula calculations is
      achieved, besides reducing potential errors; elaboration of nutrition formulas
      can be started on average 1 h and 20 minutes sooner as compared to manual
      prescription. Besides, the staff that writes down the prescription may know in
      real time the nutritional profile for each patient in the current episode and the
      patient's historic. Electronic prescription of treatment orders in this area has
      represented for our hospital an optimization of the employed resources, a
      reduction of potential errors that may occur, an improvement in consumption
      management, and an increase in the whole process quality.

PMID- 15989064
TI  - [Nutritional intervention in children and adolescents with cystic fibrosis.
      Relationship with pulmonary function].
AB  - OBJECTIVE: To assess the effects of early and continuous nutritional intervention
      in pediatric patients with cystic fibrosis (CF) and its possible implication in
      pulmonary function. PATIENTS AND METHODS: Included is the follow-up of 19
      patients with CF (11 female and 8 male children), from 17 months to 18 years of
      age, and a mean disease duration of 10 years. Genotype from 16 patients is delta
      F 508 (10 homozygotic, 6 heterozygotic). The following items have been performed
      every 2-3 months: clinical, dietary and anthropometrical assessment, classifying
      nutritional status (NS) by Z scores of weight/height, % of weight to height, body
      mass index, and Z scores of height/age. Concurrently, respiratory secretions
      culture and spirometry were obtained; and annually, biochemistry, hematologic and
      feces determinations. Nutritional intervention included: dietary recommendations,
      oral or invasive enteral nutrition (EN) and pharmacologic treatment with
      pancreatic enzymes, fat-soluble vitamins, minerals and oligoelements. RESULTS AND
      COMMENTARIES: Most of them experienced anthropometrical improvement being
      significant for weight, the relationship of weight/height and the tricipital fold
      (p < 0.05). The Z score for height has remained steady. Sixteen patients (84%)
      have developed exocrine pancreatic failure, and 3 (16%) glucose intolerance.
      Fourteen (73%) have been colonized by Pseudomonas aeruginosa. Last mean
      spirometry values were: FVC (%) 85.4 +/- 18.6 and FEV1 (%) 85.9 +/- 24.1, with a
      significant correlation between % of weight to height and FVC (coefficient 0.552,
      p = 0.022) and FEV1 (coefficient 0.625, p = 0.007). Seventy nine percent have
      required some sort of nutritional support: 3 cases (16%) invasive EN, and the
      remaining oral EN. CONCLUSIONS: Without nutritional support, many patients with
      CF do not seem to meet their demands. EN monitoring allows for and early and
      effective intervention. A close correlation has been demonstrated between
      nutritional status and pulmonary function.

PMID- 15989065
TI  - [Plasmatic and erythrocytic zinc and copper levels in critically ill patients on
      parenteral nutrition and their relationship with formulas content: preliminary
      study].
AB  - OBJECTIVES: To study in severe patients that required parenteral nutrition the
      relationship between Zn and Cu amounts present in formulas, the clinical course
      and changes in some biochemical parameters (plasmatic and erythrocytic Zn and Cu
      levels) during the parenteral nutrition therapy. PATIENTS AND METHODOLOGY: Five
      adult severe patients were studied, submitted to major abdominal surgery, and
      that required parenteral nutrition. Determinations were done for: 1) Zinc and
      copper in parenteral formulas; 2) in patients, at the beginning (T0) and at the
      end (Tf) of treatment, in erythrocytes: zinc (Zn-E) and cupper (Cu-E); in plasma,
      zinc (Zn-Pl) and in serum, cupper (Cu-S). Zinc and cupper were determined by
      means of atomic absorbance spectrometry. RESULTS: mean +/- standard deviation
      values and ranges (between brackets) were: parenteral formulas (microg/g): zinc:
      0.6 +/- 1.1 (2.2 - 7.0); Cupper: 2.4 +/- 0.7 (0.5-3.7). Biochemical parameters:
      at T0 (n = 5): Zn-E (microg/mL): 21.6 +/- 10.0 (13.6-36.1); Zn-Pl (microg/dL): 88
      +/- 72 (29-205); Cu-E (microg/dL): 113 +/- 22 (60-102); Cu-E (microg/dL): 139 +/-
      29 (106 +/- 156); Cu-S (microg/dL): 172 +/- 20 (158-195). Individual values
      compared to reference ones (normal individual from Buenos Aires with adequate
      nutrition) indicated that the three patients with favorable course normalized Zn
      Pl and Zn-E levels. However, Cu-S increased in the three cases and Cu-E in two of
      them. CONCLUSIONS: These results make clear that in the studied patients Zinc
      levels in parenteral formulas would be adequate to prevent deficiency while
      Copper levels could be too high.

PMID- 15989066
TI  - [Nutritional status assessment in a group of university students by means of
      dietary parameters and body composition].
AB  - OBJECTIVE: To assess the nutritional status in a young adults by means of dietary
      parameters and body composition. METHODOLOGY: The sample comprises 49 young men
      (35 women and 14 men) with a mean age of 21.9 +/- 2.9 ages, at Alfonso X el Sabio
      University of Madrid. Body composition was analyzed through anthropometrical
      parameters. By means of validated questionnaires, physical activity performed
      within a week was assessed, as well as energy and nutrients intake. The later was
      estimated through a registry of all foods and beverages consumed for the last 14
      days performed by each one of the participants (previously instructed) and
      estimating the amounts by weight or home or standard servings. The resting energy
      waste was determined by indirect calorimetry and through the Harris-Benedict
      predictive formula. RESULTS: Body mass index was similar in both men and women (p
      = 0.10) (23.5 +/- 1.9 and 22.0 +/- 2.8 kg/m2). The percentage of fat obtained
      through anthropometrics was 16.4 +/- 3.5% and 27.1 +/- 3.8% (p < 0.05) in men and
      women, respectively. The physical activity was light-moderate. Daily energy
      intake was appropriate for the total needs when the later were determined by
      indirect calorimetry. The caloric intake for macronutrients was unbalanced: high
      in lipids, and very low in carbohydrates. With regards to micronutrients, the
      assessed diets were in general appropriate but for folic acid, calcium, magnesium
      for both genders and vitamin A in men, with levels below the recommended ones.
      CONCLUSIONS AND RECOMMENDATIONS: In some aspects, the diet from this group
      deviates from current dietary standards. It would be advisable to increase the
      physical activity that would allow a higher food intake in order to cover for the
      insufficient intake of some nutrients without energetically unbalancing the diet.
      The assessment of resting energetic waste by indirect calorimetry seems to better
      predict the energetic needs.

PMID- 15989067
TI  - [Macronutrients intake in school teenagers in Soria capital].
AB  - OBJECTIVES: To study the macronutrients intake in Soria teenagers from 10 to 19
      years, as well as their body mass index (BMI). METHODS: A seven-day diet
      questionnaire filled in by an accidental sample of teenagers (54 boys and 56
      girls) from public schools in the capital. Working out the average daily intake
      of energy, carbohydrates, lipids and proteins by the software of "Alimentacion y
      Salud" which also gives values of individual recommended dietary allowances
      (RDAs) related to each individual's particular characteristics. Use of Student's
      t-test to compare the average values of the estimated intakes of different
      nutrients and their RDAs. RESULTS: In general, the intakes of energy, proteins
      and lipids are statistically significant over the RDAs, while the carbohydrates
      intake is under the recommendations. With reference to the type of lipids, the
      intake is over the RDAs for cholesterol, monounsaturated fatty acids, and
      saturated fatty acids, but not for polyunsaturated fatty acids. Among girls from
      13 years of age more than 12% have a higher BMI than 26 kg/m2, but between 10 and
      12 years of age more than 20% of the students have this parameter under 16 kg/m2.
      CONCLUSIONS: According to the results, it would be useful to implement some
      nutritional intervention among the adolescents in Soria capital to promote a
      healthy feeding in order to avoid possible disorders (obesity, anorexia, etc.).

PMID- 15989068
TI  - [Prognostic morbidity and mortality factors in hospital enteral nutrition:
      prospective study].
AB  - OBJECTIVE: To determine the prognostic factors that may best for see the outcome
      of an enteral nutritional intervention and to assess the assistance quality of a
      nutrition unit. SETTING AND SUBJECTS: Patients that required enteral nutrition
      during hospital admission at a third level center. INTERVENTIONS: Observational
      prospective study in which 160 patients were included by means of consecutive
      sampling, for a 6-months follow-up period. Underlying pathology, disability
      degree, nutritional assessment, type of enteral nutrition, complications, nursing
      care, and clinical course of patients were determined. RESULTS: severe caloric
      and protein hyponutrition was diagnosed in 48.4 and 52.9% of patients; stress
      degree was moderate in 52.2% and severe in 36.5%. In 88.2% of patients variation
      of protein parameters was unchanged or improved, with a 0.26 g/dL increase in
      albumin levels and 2.4 m/dL in prealbumin (p < 0.05). Multivariate analysis
      adjusted for plasma albumin at admission showed that besides this biochemical
      parameter, a severe stress degree, a decreased alertness level, and worsening of
      protein variation during admission are independent prognostic mortality factors
      during an enteral nutritional intervention in the hospitalized patient (p <
      0.05). CONCLUSIONS: alertness level, degree of caloric hyponutrition, stress
      degree, plasma albumin levels, and variation of protein parameters during
      nutritional support are independent prognostic factors for the nutritional
      intervention outcomes. The development of global monitoring systems of assistance
      activity and quality of Nutrition Units is paramount in order to improve the
      efficiency of enteral nutritional support at the hospital setting, to advance in
      patients care and promote the development of nutritional therapy.

PMID- 15989069
TI  - [Breakfast and snack of schooled adolescents in Santander].
AB  - OBJECTIVE: To study the breakfast model and food intake at mid-morning (snack) in
      schooled adolescents at Santander city. SUBJECTS: A cross-sectional study was
      performed analyzing a sample of 403 adolescents: 232 girls (58%; 95% CI: 52%-62%)
      and 171 boys (42%; 95% CI: 38%-48%), with ages between 12 and 19 years, schooled
      at 12 second degree education centers of Santander, by means of a closed
      questionnaire and a recall 24 hours later. RESULTS: Five percent (95% CI: 3.1%
      7.6%) of the adolescents referred neglecting breakfast. The most consumed foods
      were milk (47%; 95% CI: 42%-52%), chocolate milk (40%; 95% CI: 36%-45%), and
      cookies (45%; 95%CI: 36%-45%). On the other hand, 63% of adolescents consume
      whole milk (95% CI: 58%-70%), 21% semi-skimmed milk (95%CI: 17%-26%), and 11%
      skimmed milk (95% CI: 8%-15%). A decreasing lineal tendency in whole milk
      consumption is observed and a parallel increase in consumption of milks with a
      lower fat content as the academic year of adolescents advances (Armitage's chi
      square test for lineal tendency = 2.32; p = 0.02). Boys consume an average of 3.0
      (SD = 1.35) different foods during breakfast and girls 2.4 (SD = 1.20). Forty
      three percent (95% CI: 38%-48%) of adolescents have a snack, which means that 2%
      of adolescents do not have breakfast or a snack (95% CI: 1%-4%). Breakfast
      represents 18% (95% CI: 16%-19%) of the total daily energy intake, whereas for
      snack, this percentage is 16% (95% CI: 14%-17%). CONCLUSION: it is necessary to
      promote consumption of a healthy breakfast and snack that provide an appropriate
      quantitative and qualitative intake.

PMID- 15989070
TI  - [Conjugated linoleic acid lowers hypercholesterolemia but increases the risk for
      biliary lithiasis].
AB  - The term conjugated linoleic acid (CLA) refers to a series of linoleic acid
      isomers present in meat and diary products from ruminants that have their double
      bonds in a conjugated position. The aim of the present work was to study the
      effects of a CLA isomer, trans-10,cis-12, on cholesterolemia and biliary
      lithiasis risk in an animal model of diet-induced hypercholesterolemia. For that,
      two groups of hamsters were fed with a hypercholesterolemic diet supplemented
      with 0.5% linoleic acid or with the trans-10,cis-12 CLA isomer, respectively.
      Daily food intake and weight were determined and, 6 weeks later, serum and bile
      samples were obtained, and livers and spleens were dissected and weighted.
      Cholesterolemia, hepatic and splenic cholesterol content, and biliary cholesterol
      phosnolipid and bileacid concentrations were determined; Biliary Lithogenic Index
      was calculated, and presence of gallstones was assessed. CLA did not modify
      energetic intake or final body weight, spleen size or spleen cholesterol content,
      but it did significantly reduce total serum cholesterol (-18%) at the expense of
      c-LDL (-66%), and it also significantly reduced hepatic content of free
      cholesterol (-26%), without changes in esterified cholesterol. Besides, CLA
      produced a 32% increase in biliary cholesterol concentration, a 28% increase in
      Lithogenic Index, and a higher incidence of biliary lithiasis. Therefore, the
      present study shows that the CLA trans-10,cis-12 isomer is hypercholesterolemic
      since it increases, at least in part, cholesterol secretion to the bile. As a
      consequence, this effect increases the risk for biliary lithiasis.

PMID- 15989071
TI  - [Probable hypersensitivity reaction to parenteral nutrition: report of a case].
AB  - A probable case of hypersensitivity reaction to Total Parenteral Nutrition (TPN)
      in a 55 years old patient diagnosed with gastric adenocarcinoma is presented.
      Onset of TPN infusion coincides with the time of the onset of a disseminated
      pruritic cutaneous eruption that repeats after a second exposure to nutrition.
      The likely causes of this hypersensitivity reaction are analyzed.

PMID- 15989072
TI  - Benign EEG variants.
AB  - EEG is a valuable tool that assists in the accurate diagnosis of seizure
      disorders. The precise interpretation of EEG requires an ability to recognize
      patterns that are benign in nature but may be misinterpreted as indicative of a
      seizure tendency. This review will summarize benign variants encountered in adult
      EEGs including: small sharp spikes, wicket spikes, fourteen- and six-hertz
      positive bursts, six-hertz spike and wave, rhythmic temporal theta bursts of
      drowsiness, subclinical rhythmic electroencephalographic discharge in adults, and
      midline theta rhythms. Although most of these patterns are relatively uncommon,
      it is imperative that the clinical neurophysiologist identifies them as benign
      variants.

PMID- 15989073
TI  - Regional attenuation without delta (RAWOD): a distinctive EEG pattern that can
      aid in the diagnosis and management of severe acute ischemic stroke.
AB  - Acute thrombolysis with recombinant tissue plasminogen activator (tPA) is the
      only treatment of proven effectiveness in acute ischemic stroke (AIS). Cerebral
      edema (CE) is the most feared and fatal complication of AIS. For both of these
      conditions, patient selection for treatment and timing of intervention are
      crucial but controversial issues. Conventional diagnostic tools for AIS,
      including the neurological exam, computerized cerebral tomography (CT) Scan, and
      magnetic resonance imaging (MRI) have not as yet been able to determine which
      patients are the best risk-benefit candidates for thrombolysis, nor are they
      sensitive to the early detection of patients at risk for cerebral edema. This
      article suggests that the use of Emergency EEG (EmEEG) in AIS can reveal a
      distinctive EEG pattern that adds value to the selection of patients for
      thrombolytic and cerebral edema treatment. This pattern, called RAWOD (Regional
      Attenuation WithOut Delta) can identify patients with massive AIS earlier than CT
      or MRI. Patients with RAWOD are unlikely to benefit from thrombolysis but may be
      candidates for early surveillance and intervention for cerebral edema.

PMID- 15989074
TI  - How some drugs affect the electroencephalogram (EEG).
AB  - The effects of drugs on the EEG vary and are often dose dependent. In general,
      drugs effects on the EEG are fairly predictable and include: no effect,
      accentuation of beta activity, background slowing with decreased amplitude and/or
      frequency of the alpha rhythm, intermixed theta and/or delta activity, decreased
      seizure activity, and lowering of the seizure threshold with increased spike and
      wave discharges. In severe overdose cases, the EEG may demonstrate alpha/theta
      coma, burst suppression, or even a "flat" EEG pattern.

PMID- 15989075
TI  - Hurst exponents and linear regression with an application to low-power beta
      characterization in meditation EEG.
AB  - A lever-like EEG feature-extraction method based on the Hurst exponent and
      regression-fitting errors is proposed for identifying beta rhythms. The proposed
      method is superior to most methods using the time- and frequency-domain feature
      extraction parameters for identifying beta rhythms.

PMID- 15989076
TI  - Low impedances: how important are they with digital recordings?

PMID- 15989077
TI  - Waveform Window.

PMID- 15989078
TI  - Modification by L-NAME of codeine induced analgesia: possible role of nitric
      oxide.
AB  - Objectives were to investigate the effect of nonselective nitric oxide synthase
      (NOS) inhibitor, L-NAME on codeine-induced analgesia and to see the role of NO in
      its antinociceptive effect. Also, to see if L-NAME can potentiate the
      antinociceptive response of sub-effective dose of codeine and to explore if
      opioid receptors have some role to play in L-NAME effects. Mice were injected
      with selected doses of codeine or other selected agents intraperitoneally and the
      latency to hot plate was recorded at zero, 15, 30, and 60 min of the treatments.
      The antinociceptive response of codeine (10 mg/kg, i.p.) was studied in
      comparison to those of the NOS inhibitor, L-NAME, and of nitric oxide donor,
      sodium nitroprusside (SNP). Assessment of nitrates and nitrites (NOx) in the sera
      of treated mice were also made. Codeine (20 mg/kg dose), induced analgesia
      significantly and dose dependently only after 15 min. L-NAME at 20, 40, and 80
      mg/kg dose levels significantly changed the nonanalgesic effect of codeine (10
      mg/kg) to highly significant analgesia. The effect of L-NAME 40 mg/kg was
      significantly higher than the other two doses and was almost equal to that of the
      higher dose of codeine. Naloxone itself did not show any intrinsic effect but
      almost abolished the L-NAME-codeine induced analgesia. Similarly, SNP (1 mg/kg)
      reversed the decrease in reaction time by L-NAME-codeine to its control values,
      significantly. Pretreatment with L-NAME rendered the nonanalgesic dose of codeine
      significantly analgesic almost in an equal potency to the high dose of codeine
      alone and indicate that the NO modulatory effect on the opioid analgesic codeine
      is probably, at least in part, through opioid receptors.

PMID- 15989079
TI  - Effects of losartan on blood pressure, oxidative stress, and nitrate/nitrite
      levels in the nitric oxide deficient hypertensive rats.
AB  - Losartan, an angiotensin II type-1 receptor (AT1) antagonist, was used to
      investigate whether it can offer protection against the sustained hypertension,
      cardiac hypertrophy, and renal damage induced by chronic inhibition of nitric
      oxide (NO) by Nomega-nitro-L-arginine methyl ester (L-NAME). We studied the
      involvement of both NO metabolism and oxidative stress in L-NAME-induced
      hypertension, and how AT1 receptor antagonism may interact. Male Wistar albino
      rats were subjected to NO synthesis inhibition by the use of L-NAME (60
      mg/kg/day), and the effects of losartan (10 mg/kg/day) in drinking water for six
      weeks were observed. After six weeks, animals were subjected to the measurements
      for systolic, mean, and diastolic blood pressure (BPs, BPm, and BPd,
      respectively). Under light ether anesthesia blood was withdrawn for ACE activity,
      NOx and creatinine determinations. Heart and kidneys were weighed, and organ
      indices were calculated comparing to their body weights. These tissues were
      immediately preserved for GSH, MDA, NOx estimations. Chronic L-NAME treatment
      raised BPs, BPm, and BPd, respectively, above the normal. Treatment also
      increased NOx in plasma, significantly decreased it in the heart, and tended to
      increase it in kidney. L-NAME caused GSH depletion in the heart and kidney
      tissues with a concomitant increase in MDA contents in both the tissues. Plasma
      creatinine doubled in L-NAME-treated animals. Plasma ACE activity showed a
      nonsignificant decrease below control. Concurrent treatment with losartan almost
      completely inhibited any rise in blood pressure. Losartan replenished the partly
      depleted cardiac and renal antioxidant GSH and ameliorated the increase of
      oxidative stress damage index, MDA. However, losartan alone did not change
      appreciably the plasma level or cardiac and renal contents of NO,. Losartan plus
      L-NAME treatment caused an increase in plasma ACE activity above control.
      Furthermore, losartan ameliorated the L-NAME induced increase in creatinine back
      to value nonsignificantly different from control.

PMID- 15989080
TI  - High efficiency activation of L-type Ca2+ current by 5-HT in human atrial
      myocytes.
AB  - In human atrial myocytes, serotonin rather than sympathetic, stimulation is more
      frequently associated with atrial fibrillation. So does the arrhythmogenic effect
      of serotonin result from the mechanism of action of the receptor or the context
      of its action upon cardiac myocytes? The capacity of agonists to produce cAMP
      followed the sequence 5-HT < Iso < Forskolin to increase ICaL with 5-HT = Iso =
      Forskolin. The simultaneous application of threshold concentrations of 5-HT and
      Iso maximally increased ICaL. We will show that the effect of 5-HT upon human
      atrial myocytes is an imbalance between low production of cAMP and maximal
      activation of ICaL.

PMID- 15989081
TI  - Regulation of receptor-coupling to (multiple) G proteins. A challenge for basic
      research and drug discovery.
AB  - G protein-coupled receptors induce intracellular signals via interaction of with
      cytosolic/peripheral membrane proteins, mainly G proteins. There has been much
      debate about the mode of interaction between the receptors, G proteins and
      effectors, their mobility and the ways of determining the specificity of
      interaction. Additional complexity has been added to system upon the discovery of
      i) coupling of single receptors to several G proteins and ii) active direction of
      this by different ligands (stimulus trafficking). These data suggest that the
      most primary unit in the signal transduction is the receptor complexed with a
      specific G protein, making the investigation of the mechanism of receptor-G
      protein selection and interaction even more important. In this review, I will
      summarize the general knowledge of receptor interaction with G proteins and
      effectors and the ways of investigating this.

PMID- 15989082
TI  - Human gastric tissues simultaneously express the classical and alternative
      splicing cholecystokinin-B/gastrin receptors.
AB  - To explore whether cholecystokinin-B/gastrin receptor (CCKBRwt) gene and its
      alternative splicing variant preserving intron 4 (CCKBRi4sv) are expressed in
      human gastric carcinoma cell line and tissue, we detect mRNA expression of
      CCKBRwt and CCKBRi4sv in 30 gastric carcinoma and their corresponding normal
      tissues, 10 gastritis, and 2 autopsied normal stomach specimens as well as in a
      gastric carcinoma cell line SGC-7901 cells by RT-PCR and sequencing. The results
      revealed that human normal, inflammatory, and malignant gastric tissues
      simultaneously expressed the classical and alternative splicing cholecystokinin
      B/gastrin receptor genes. The alternative splicing variant contains the intron 4
      of cholecystokinin-B/gastrin receptor gene.

PMID- 15989083
TI  - Integrating service learning into a curriculum to reduce health risks at
      alternative high schools.
AB  - Service learning has been identified as a promising approach to reduce sexual
      risk behavior, among other outcomes. This study used qualitative data analysis to
      offer suggestions for optimally integrating service learning into a program to
      reduce sexual risks among alternative school students. Data were collected from
      student participants in the All4You! Project using classroom materials, focus
      groups, and individual interviews. Project educators and project staff also
      provided data through summary forms and field notes. Qualitative data analysis
      revealed 5 strategies for creating positive service experiences for alternative
      school students: (1) find appropriate service-learning sites, (2) create staff
      support, (3) maintain appropriate student participation and behavior; (4) enhance
      student reflection on service-learning experiences, and (5) address students'
      self-images.

PMID- 15989084
TI  - Models for delivering school-based dental care.
AB  - School-based health centers (SBHCs) often are located in high-need schools and
      communities. Dental service is frequently an addition to existing comprehensive
      services, functioning in a variety of models, configurations, and locations.
      SBHCs are indicated when parents have limited financial resources or inadequate
      health insurance, limiting options for primary care and preventive services, or
      within low-access areas such as dental health professional shortage areas. Poor
      health and concomitantly poor oral health can lead to attendance problems. Oral
      health services in school-based setting are often the only access to services a
      child may have. Children who attend schools with SBHCs have immediate access to
      services that are coordinated with the student'sfamily and school personnel or
      administrators. Comprehensive services can be collaborative, with support or
      administration provided by more than 1 organization. For example, the Children's
      Aid Society (CAS), Columbia University School of Dental and Oral Surgery
      (CUSDOS), and Columbia University Mailman School of Public Health developed,
      implemented, and currently operate SBHCs in 2 communities in the northern
      Manhattan section of New York City (Central Harlem and Washington
      Heights/Inwood). The clinics operate in or are affiliated with public schools in
      New York City. All CAS and Columbia University sites include dental components,
      using a variety of delivery models. Determining which dental delivery system to
      use for a particular community or population is a complex decision. The models,
      reasons for selection, and sustainability of each system are described.

PMID- 15989085
TI  - A qualitative study of Mexican American adolescents and depression.
AB  - Depressive disorders are present in a high percentage of Mexican American
      adolescents. Among the US Mexican American population, suicide is the fourth
      leading cause of death among 10- to 19-year-olds. Little research, however, has
      focused on Mexican American adolescents' knowledge and views about depression and
      seeking help for depression. Results from a qualitative study on Mexican American
      adolescents' attitudes about depression are investigated in this paper. Sixty
      five high school and middle school students in a largely Mexican American, urban
      school district in San Antonio, Tex, participated in 9 semistructured, focus
      group interviews where participants were asked questions to elicit their
      understanding of depression, treatment for depression, and words used to describe
      it. Coding of salient words and themes from transcribed interviews were entered
      into Atlas. ti for qualitative analysis. Three themes emerged: (1) adolescents'
      definitions of depression, (2) beliefs about adolescent depression, and (3)
      treatment for adolescent depression. While depressive symptoms among Mexican
      American adolescents are common and recognized, resource and treatment knowledge
      is scarce. An understanding of the beliefs, attitudes, and knowledge of these
      adolescents can provide crucial information about the content and structure of a
      universal, school-based, peer-facilitated depression awareness program.

PMID- 15989086
TI  - Protecting you/protecting me: effects of an alcohol prevention and vehicle safety
      program on elementary students.
AB  - This paper describes an evaluation of Protecting You/Protecting Me (PY/PM), a
      classroom-based, alcohol-use prevention and vehicle safety program for elementary
      students in first through fifth grades developed by Mothers Against Drunk
      Driving. PY/PM lessons and activities focus on teaching children about (I) their
      brains (why their brain is important, how their brain continues to develop
      throughout childhood and adolescence, what alcohol does to the developing brain,
      and why it is important to protect their brain); (2) vehicle safety (what to do
      to protect themselves should they ever ride with an impaired driver); and (3)
      life skills (decision making, stress management, and media literacy). Fourth- and
      fifth-grade students from schools in the fourth year of PY/PM implementation were
      surveyed. Results indicated that, relative to comparison students from matched
      schools, PY/PM students increased their knowledge of alcohol's effect on
      development; gained decision-making, stress-management, and vehicle safety
      skills; and demonstrated changes in attitudes toward underage alcohol use and its
      harm. Further, students retained lessons learned in previous years and their
      scores improved with increased exposure to PY/PM. In addition, the findings
      demonstrate that it is possible to design and implement a program that can
      improve young children's knowledge regarding alcohol and their developing brains,
      teach them skills to protect themselves in dangerous situations, increase already
      high antialcohol attitudes, and change perceptions of alcohol's harmfulness.

PMID- 15989087
TI  - Adolescent exposure to and perceptions of environmental tobacco smoke.
AB  - Environmental tobacco smoke (ETS) poses an underappreciated risk to adolescent
      health. This study examined perceptions of adolescents (n = 574) regarding ETS.
      About one half (54%) were exposed to ETS the previous week, and one third (30%)
      were exposed to 3 or more hours of ETS the past week. Concurrently, 29% believed
      that breathing someone else's cigarette smoke had little or no effect on their
      health. Most adolescents (56%) believed that smoking should not be allowed in
      restaurants without bars but were less supportive of prohibiting smoking in
      restaurants with bars (20%) or in bars (14%). Two thirds (69%) of adolescents
      believed that the government should be involved in making laws that protect the
      health of people who work in bars and restaurants. Almost one half (49%) believed
      that the government should be involved in passing laws that make it illegal for
      people to smoke in public places. Odds ratios revealed that females, nonwhites,
      younger students, nonsmoking students, and students who believed that ETS
      exposure had a moderate or major effect on health were statistically
      significantly more likely to support clean indoor air ordinances in select
      locations compared to males, whites, older students, students who smoke, and
      students who perceived that ETS exposure has little to no effect on health.

PMID- 15989088
TI  - Let's sell health!

PMID- 15989089
TI  - Recruitment strategies for the Princeton (Ohio) City School District
      epidemiological study.

PMID- 15989090
TI  - [Advances in brachytherapy].

PMID- 15989091
TI  - [Testicular tumors: association between preoperative clinical, radiological and
      immuno-serological factors, and histology and stage].
AB  - OBJECTIVES: To evaluate and quantify the association between clinical, ultrasound
      and immunoserological data and histologic type and stage of testicular tumors.
      METHODS: We analyze a cohort of 80 patients who underwent orchiectomy for
      testicular neoplasia. Mean patient age was 30.4 years. Past medical history,
      first symptoms, time from first symptom to operation, physical examination and
      ultrasound data, and preoperative serum levels of alpha-fetoprotein and beta HCG
      were retrospectively collected. RESULTS: Patients with non seminomatous germ cell
      tumor (NSGCT) had a significantly lower mean age (23.7 yr.) than patients with
      pure seminoma (41.3 yr.), and these latter a significantly lower age than
      patients with non germinal tumors (50.7 yr.). Initial presentation with general
      malaise or lumbar pain increased 2.56 times the relative risk of having a tumor
      in advanced stage (higher than stage I) . Presence of gynecomastia increased 16.5
      times the relative risk of having a non germ cell tumor, due to the inclusion of
      Leydig's tumors in this group. Detection of heterogeneous nodules by ultrasound
      increased 4.5 times the risk of having a non seminomatous germ cell tumor.
      Preoperative elevation of alpha-fetoprotein ruled out the existence of seminoma
      and non germ cell tumor; whereas preoperative elevation of beta HCG increased
      3.21 times the risk of having a non seminomatous germ cell tumor. No significant
      association was shown between preoperative tumor markers and tumor stage.
      CONCLUSIONS: The existence of gynecomastia, age, detection of heterogeneous
      nodules on ultrasound, and preoperative alpha-fetoprotein and beta HCG are
      relevant data in relation to histological type of tumor. Lumbar pain or malaise
      are clinical data associated with tumor stage.

PMID- 15989092
TI  - [Surgical treatment of renal adenocarcinoma with venous thrombus].
AB  - OBJECTIVES: To analyze therapeutic management and survival of renal
      adenocarcinoma with tumor venous extension treated by surgery in our experience.
      METHODS: We retrospectively evaluate a series of 29 cases of renal adenocarcinoma
      with venous thrombus who underwent radical nephrectomy and thrombectomy from
      January 1986 to November 2003. Mean age was 63.4 11.9 (29-79) years. 23 patients
      were males (79%) and 6 (21%) females. 17 (59%) patients had the tumor in the
      right kidney and 12 (42%) in the left kidney. Tumor thrombus level was: Level I
      (renal vein-inferior vena cava) 13 (45%), Level II (infrahepatic vena cava) 9
      (31%), Level III (retrohepatic vena cava/suprahepatic) 3 (10%), and Level IV
      (auricula) 4 (14%). 92% of the cases presented perirenal fat involvement.
      Survival analysis was performed including 24 cases of the 29. We analyzed overall
      and cancer-specific survival, as well as possible influence of tumor thrombus
      level, fat involvement, and tumor grade as prognostic factors. RESULTS: Mean
      tumor size was 8.15 +/- 2.25 cm (5-13). Surgical approach was purely abdominal in
      23 cases (79%) and thoraco-phreno-laparotomy in 6 (21%). Hepatic mobilization
      maneuvers and hepatic pedicle clamping were performed in 5 (17%) patients. Venous
      clamping was: renal-cava 13 cases (44%), triple clamping I1 (37%) (9 infrahepatic
      and 2 suprahepatic), and supradiaphragmatic-auricula 5 (17%). Conventional
      extracorporeal circulation (CEC) with moderate hypothermia (26-28 degrees C) was
      employed in 4 cases and CEC with heart arrest (4 min) in one. Mean follow-up was
      52 months. At the time of review 9 patients were alive, 11 had died from tumor
      and 4 had died from other causes. Mean overall survival was 71 +/- 12 months and
      cancer specific survival 86 +/- 14 months. Neither renal fat involvement (p=0.6)
      nor tumor thrombus level (p = 0.9) were prognostic factors for survival in the
      univariant analysis, but tumor grade was (p = 0.03). CONCLUSIONS: Patients with
      venous tumor extension without lymph node involvement or metastasis should be
      treated by radical surgery with complete excision of the tumor thrombus. Tumor
      grade was a prognostic factor for survival, but venous involvement level and
      presence of perirenal fat involvement were not.

PMID- 15989093
TI  - [Subcapsular orchiectomy in the treatment of prostate cancer: results].
AB  - OBJECTIVES: To analyze the role of orchiectomy in the management of metastasic
      prostate cancer in our environment. METHODS: We studied 76 patients with the
      diagnosis of prostate cancer who underwent subcapsular orchiectomy. RESULTS: Mean
      age was 72 years, median Gleason score was 7, and only 17% had organ confined
      tumors. Mean follow-up was 2.3 yr. and hospital stay median three days. Ten of
      the 76 patients in the study died from cancer, being overall five-year survival
      75%. Regarding cost analysis, surgical castration was cheaper in the long-term
      but has the disadvantage of its greater psychological impact. CONCLUSIONS:
      Orchiectomy is a valid hormonal blockade option when estimated patient survival
      is longer than one year.

PMID- 15989094
TI  - [Filling phase abnomalities and cystocele].
AB  - OBJECTIVES: To evaluate the clinical and urodynamic characteristics of a series
      of women with lower urinary tract symptoms (bladder filling phase) presenting
      various rates of cystocele. METHODS: 119 female patients were included in this
      study; mean age was 55.8 yr. (range 15-87). All patients underwent urogynecologic
      physical examination (cystocele was graded 0-3) and complete urodynamic study.
      Urodynamic terminology and measurements comply with the ICS (InternationaL
      Continence Society) standards. Statistical significance was established below
      0.05. Quantitative variables were compared by the Student's t and non parametric
      variables by Pearson's chi-square. RESULTS: The most frequently reported symptom
      was urinary incontinence when coughing (77/118, 65.3%), followed by urge
      incontinence (71 patients, 60.2%). The grade of cystocele was 0 in 31.1%, 1 in
      25.2%, and 2 in 26.1%, and 3 in 17.6%. There was a statistically significant
      association between grade of cystocele and the symptom "vaginal bulge"
      (p=0.00002). The presence of cystocele did not show any statistical association
      with lower urinary tract symptoms of the filling phase. Mean cystomanometric
      bladder capacity was 224.8 ml. Involuntary contractions of the detrusor muscle
      appeared in 38 cases (21.9%), stress urinary incontinence in 19 (16%), mixed
      incontinence in 8 (6.7%) and absence of evidence of urinary incontinence in 58
      (48.7%). Patients with urgency had a lower bladder capacity than patients without
      it (p = 0.02), as did patients with urge incontinence (p = 0.02). Nocturia (p =
      0.05), urgency (p = 0.02) and urge incontinence (p = 0.01) were significantly
      associated to bladder capacity. The existence of involuntary contractions was
      statistically associated with urge incontinence (p = 0.01). Patients with
      involuntary contractions during the filling phase showed increased diurnal
      voiding frequency (p = 0.02), as well as patients without a stress urinary
      incontinence (p = 0.04) and cases without a stress urinary incontinence (p =
      0.04). The symptom incontinence with coughing had a significant statistical
      association with the urodynamic diagnosis of stress urinary incontinence (p=
      0.01). Bladder capacity was augmented in grade 3 cystocele (p = 0.003). The
      existence of cystocele was not associated with bladder hyperactivity (p = 0.65),
      neither was the diagnosis of a stress urinary incontinence (p = 0.37).
      CONCLUSIONS: No relationship has been demonstrated between existence and degree
      of cystocele and functional lower urinary tract symptoms of the filling phase, on
      the one hand, and urodynamic evidence of bladder hyperactivity and incontinence
      on the other hand. This could have important therapeutic implications.

PMID- 15989095
TI  - [Factors for voiding dysfunction and cystocele].
AB  - OBJECTIVES: To evaluate the clinical and urodynamic features of a series of women
      with post void residual urine (disbalanced voiding) and various degrees of
      associated cystocele. METHODS: 119 female patients were studied by clinical
      evaluation, urodynamics, and imaging tests (VCUG). All patients underwent history
      and genitourological examination (evaluating cystoceles from grade o to 3), neuro
      urological examination, and complete urodynamic study. Fifty patients (42%)
      underwent radiological studies of the upper urinary tract. Disbalanced voiding
      was defined as existence of post void residual greater than 20% of the voided
      volume. Urethral resistance was measured by URA. Structural obstruction was
      characterized by PURR (CHESS classification). Functional obstruction was studied
      by DURR and perineal EMG (associated with flowmetry). Detrusor contractile power
      was evaluated by W max, W 80-20, and duration of contraction. Urodynamic
      terminology and measurements complied with the International Continence Society
      (ICS) standards. Statistical significance was established at 0.05. Statistical
      analysis was done by Student's t for quantitative variables, and Pearson's chi
      square for non parametric variables. RESULTS: 119 patients were enrolled. Mean
      age was 55.84 yr. (range 15-87). Regarding post void residual (114 valid
      uroflowmetry studies), 25 patients were classified as voiding disbalance (21.9%)
      and 89 as balanced (74.8%). Regarding clinical data, there were only significant
      differences between groups in voiding difficulty. For uroflowmetry, only the
      percentile of the Maximal flow (Qmax) showed significant differences (35 vs. 22
      for balanced/disbalanced voiding respectively, p = 0.02). Pressure/volume studies
      demonstrated bladder hyperactivity in 16 cases (64%) in the group of disbalanced
      voiding and 31 cases (34.8%) in the normal voiding group (p = 0.008), which
      presented associated with increased urethral resistance (URA)(p = 0.01) . In the
      pressure/flow study, there were significant differences in the URA (14.7 vs.
      25.3, p = 0.001). There were statistically significant differences in the degree
      of constrictive (0.5 vs. 1.1, p = 0.009) and compressive (0.5 vs. 1.1; p = 0.04)
      obstruction (Chess classification). There were not significant differences in the
      analysis of isometric contractility (Wmax), but there were in the isotonic
      contractility (W80-20) and detrusor contraction duration. These latter
      differences presented significant association with the degree of cystocele. DURR
      and perineal EMG data did not show differences between groups. Radiological
      abnormalities of urethral morphology were statistically different between groups,
      presenting in 10% of the patients with normal voiding and 50% of the disbalanced
      voiding group, although there was not statistical association with obstruction (p
      = 0.64). The existence of cystocele did not show a statistical association with
      these variables either. CONCLUSIONS: Disbalanced voiding appeared with organic
      obstruction of the lower urinary tract (constrictive most significantly), as well
      as detrusor abnormal contractility, but whereas the first was not significantly
      associated with presence and grade of cystocele, the second showed such
      association.

PMID- 15989096
TI  - [Epididymal cysts in childhood].
AB  - OBJECTIVES: To retrospectively review all cases of epididymal cysts registered
      over the last five years; 15 cases have been included. Simple epididymal cysts
      are a rare pathology in childhood, being most of them diagnosed in puberty.
      Currently, due to the scarce case series, there is not consensus about the most
      adequate therapy. METHODS/RESULTS: Mean age at presentation was 11.5 yr. (1-16).
      50% were diagnosed incidentally and 29% presented increased scrotal size. 46% of
      the cases had associated left varicocele (n = 6) and 26% had history of
      orchiepididymitis. Diagnosis was based on physical examination and confirmed by
      ultrasound. 40% of the patients underwent surgery and the remainder received
      conservative treatment without evidence of complications on follow-up.
      CONCLUSIONS: Due to the benign character and good evolution of all cases of
      epididymal cysts treated conservatively and the absence of benefit after surgical
      treatment, we believe that management should be conservative with clinical and
      ultrasound controls, leaving surgery for cysts with complications. The frequent
      association between epididymal cysts and varicocele is related to coincidence of
      both pathologies in the prepuberal age.

PMID- 15989097
TI  - [Stone Cone: a device that prevents ureteral stone migration during
      intracorporeal lithotripsy].
AB  - OBJECTIVES: Proximal migration of stone fragments during ureteroscopic
      lithotripsy is a common problem influenced by pressure of irrigation solution,
      type of energy for lithotripsy, site and degree of fixation of the stone to the
      ureteral wall, and degree of proximal ureteral dilation. The Stone Cone (Boston
      Scientific & Spencer) is a device that helps to prevent proximal migration of
      fragments and favours a safe extraction during ureteroscopic lithotripsy.
      TECHNIQUE: The Stone Cone is an helical device made of stainless steel and
      nitinol alloy, which consists of an internal guide wire and a sheath-like
      radiopaque catheter with a 3 Fr. calibre. Once the cone is placed above the stone
      it is maintained in that position during lithotripsy to avoid fragment migration.
      The external catheter is used to coil and unroll the cone, and allows access to
      place the cone above the stone. METHODS: We describe two cases of urinary calculi
      in the left lumbar ureter treated by ureteroscopy and intracorporeal lithotripsy
      with holmium YAG laser using the Stone Cone to avoid migration of fragments.
      RESULTS: One month after surgery no lithiasic fragments were observed in the
      imaging tests. CONCLUSIONS: The Stone Cone decreases the need to perform repeated
      ureteral instrumentations, and is also a safer and simpler method for the
      extraction of stone fragments. The use of Stone Cone seems to have more
      advantages than Dormia's basket during ureteroscopic lithotripsy in terms of
      lower incidence of residual fragments and reoperation rate.

PMID- 15989098
TI  - [Transurethral resection with saline solution: a technological achievement not
      yet assimilated by the urological community].
AB  - OBJECTIVES: To objectively demonstrate the advantages provided by TURP with
      saline solution (an adjustment made possible thanks to the technological
      development of new high frequency current generators), although it surprisingly
      has been received with scepticism in the urological community. METHODS: A first
      group of 51 patients (group A) underwent low hydraulic pressure TURP with a
      pulsed bipolar system (Gyrus Plasmakinetic, with large loop) using physiologic
      saline solution as irrigation. A second group of 49 patients underwent low
      hydraulic pressure TURP with a conventional monopolar system (Erbe 350) using
      glycine-ethanol solution. RESULTS: A better surgical performance was obtained in
      the first group, as well as a lower degree of bleeding. No intraoperative
      complications appear in either group. Only one case of late hematuria was
      registered one month after surgery in a patient of group A. CONCLUSIONS: Pulsed
      bipolar TURP has a minimal thermal in-depth diffusion, achieves vessel hemostasis
      by dessication instead of charring, has an extremely precise cutting quality,
      does not produce neuromuscular stimulation, and makes the use of saline solution
      irrigation possible. All these translate to lower tissue injury, null risk of
      sequelae secondary to electric current leak, a finer technique, a lower risk of
      accidental perforation, and the possibility of duplicate or triplicate the
      surgical time without risk, especially when working with low hydraulic pressure.

PMID- 15989099
TI  - [Secondary bladder amyloidosis with severe recurrent hematuria: transurethral
      Mickuliz procedure as hemostatic option].
AB  - OBJECTIVES: Primary localized amyloidosis of the urinary bladder generally has a
      benign course. On the contrary, secondary amyloidosis, a consequence of systemic
      amyloidosis, may have massive bleeding and produce complications such as bladder
      rupture or life-threatening hemodynamic problems requiring desperate hemostatic
      procedures such as hypogastric artery embolization or ligature, or cystectomy. We
      report one case in which hemostasis was achieved by a Mickulicz transurethral
      bladder tamponage. METHODS: 58 year old female with very aggressive rheumatoid
      arthritis and secondary renal amyloidosis under chronic hemodialysis presenting
      with severe hematuria after hip replacement. An inflamed bladder was found, the
      biopsy of which showed edema in all layers with blood vessel walls enlarged by
      amiloyd deposits. After several unsuccessful transurethral hemostatic procedures,
      intravesical formalin irrigation was carried out together with a Mikulicz type
      gauze packaging after urethral dilation. The gauze was withdrawn three days later
      without bleeding recurrence; however she presented subsequent neurological
      impairment and finally died 14 days after the last urological procedure.
      CONCLUSIONS: Transurethral packaging of the urinary bladder in a woman with
      massive hematuria is a hemostatic option that we recommend to be used before
      other more dramatic or invasive options are chosen.

PMID- 15989100
TI  - [Ureteral actinomycosis. Case report].
AB  - OBJECTIVES: To report one case of pseudotumoral lesion of the iliac ureter with
      obstructive uropathy leading to loss of function of the renal unit. METHODS: 66
      year-old male being studied for BPH who presents with a self-limited
      monosymptomatic hematuria. RESULTS: Renal ultrasound detected grade II
      pyelocaliectasis of the right kidney. IVU showed absence of function of the right
      kidney. Urine cytology was consistent with low-grade transitional cell carcinoma.
      Percutaneous nephrostomy was performed confirming irreversible function loss.
      Antegrade pyelography showed a filling defect in the right iliac ureter. Radical
      nephroureterectomy with bladder cuff was carried out with good results. Pathology
      reported chronic pyelonephritis and parietal inflammatory lesion of the ureter
      obliterating the lumen with inflammatory infiltrates, urothelial erosion and
      presence of actinomyces. CONCLUSIONS: Actinomycosis is a chronic bacterial
      infection, with A. israeli being the most common pathogen. It is part of the
      normal flora of the oral cavity and GI tract, and cervical-facial region is the
      most frequent clinical involvement (60% of the cases). Urinary tract infection is
      exceptional. No other focus was found in the long-term follow-up.

PMID- 15989101
TI  - [Subepithelial hematoma of the renal pelvis producing a filling defect in the
      upper urinary tract radiological study].
AB  - OBJECTIVES: After taking care of a patient with suspicion of upper urinary tract
      neoplasia which was finally diagnosed of renal pelvis subepithelial hematoma
      (Antopol-Goldman lesion), we decided to review such unfrequent pathology with the
      aim to summarize its main characteristics. METHODS: The patient presented
      clinically and radiologically as an upper urinary tract tumor and underwent
      nephroureterectomy. Past history was significant for oral anticoagulative
      treatment after deep vein thrombosis. RESULTS: Pathologic study of the
      nephrectomy specimen reported absence of urothelial tumor and presence of a
      subepithelial hematoma of the renal pelvis, which explained both clinical
      manifestations and radiological findings. Our case is very similar to the other
      27 published in the bibliography. CONCLUSIONS: Subepithelial hematoma of the
      renal pelvis is a benign lesion, more frequent in females, which appears between
      the fourth and sixth decades of life. Not much is known about its
      etiopathogenesis, it probably is a multifactorial process. It simulates an upper
      urinary tract urothelial tumor, both clinically and radiologically, and so is
      treated in most published cases. It is necessary to know this entity as possible
      differential diagnosis of upper urinary tract radiological study filling defects
      to avoid non necessary nephrectomies.

PMID- 15989102
TI  - [Renal carcinoma and ipsilateral pheochromocytoma].
AB  - OBJECTIVES: To report one case of associated renal cancer and ipsilateral
      pheochromocytoma treated by laparoscopic surgery METHODS: We describe the case of
      a 67-year-old female presenting with left lumbar pain and recurrent urinary tract
      infections. Ultrasound and abdominal CT scan were performed revealing renal
      carcinoma and ipsilateral adrenal mass, which was confirmed by MRI. With the
      diagnosis of left renal carcinoma and possible adrenal metastasis, laparoscopic
      left nephrectomy and adrenalectomy were performed. RESULTS: Pathologic study of
      the specimen reported a chromophobic renal cell carcinoma and adrenal
      pheochromocytoma. CONCLUSIONS: The association of renal carcinoma and
      pheochromocytoma is unfrequent, as suggested by the limited available
      bibliography on the topic. The presence of an adrenal mass in a patient with
      history of primary tumor is frequently secondary to metastasic disease, although
      primary adrenal neoplasia should not be discarded.

PMID- 15989103
TI  - [Giant adrenal myelolipoma].
AB  - OBJECTIVE: We report a case of a giant myelolipoma of the adrenal gland
      METHODS/RESULTS: A case of a giant myelolipoma of the adrenal gland, an uncommon
      non-functioning tumour of the adrenal cortex comprised of haematopoietic and
      adipose tissue, that had been detected incidentally during evaluation with CT
      because of its characteristic fatty composition. The clinical features, diagnosis
      and treatment are discussed.

PMID- 15989104
TI  - [Cryptorchidism and cancer].
AB  - OBJECTIVES: To demonstrate the presence of neoplasic degeneration within non
      descended testicles and the effect that late orchydopexy could have in the
      increased incidence. METHODS: We review the medical records of 22 patients with
      the diagnosis of malignant testicular tumor cared for at the Department of
      Urology of the Hospital CQ D Comandante M. Fajardo between 1982 and 2004, looking
      for history of cryptorchidism, age at the time of orchydopexy (if carried out),
      histological diagnosis and stage, and post operative outcome. We include one case
      which did not belong to this series because it was not reported previously.
      RESULTS: Four patients with history of cryptorchidism were found, the youngest
      was 12 years old and the time of orchydopexy and the oldest 57. All cases of
      testicles outside the scrotum at the time of diagnosis were seminomas. The only
      case with successful orchydopexy presented teratocarcinoma and died before two
      years from orchiectomy. All cases of seminoma received radiotherapy and are
      disease-free with negative tumor markers. CONCLUSIONS: Cryptorchid testicles
      operated after the age of two years only provide hormonal supply adequate for
      development of secondary sexual features but not fertility, so that in unilateral
      cases late orchydopexy would only help to detect neoplasic degeneration before
      the appearance of pain or symptoms from metastases. If there are not important
      psychological or cosmetic reasons orchiectomy should be the first therapeutic
      option for adult's cryptorchidism.

PMID- 15989105
TI  - [Unusual ureteral iatrogenic disease].

PMID- 15989106
TI  - [Extremely premature infants--survival and lifespan at the limits of
      feasibility].

PMID- 15989107
TI  - [Survival is not referred to as viable in premature births: what have we been
      expecting?].

PMID- 15989108
TI  - [Perinatology--quo vadis?].

PMID- 15989109
TI  - The multiple functions of Tamm-Horsfall protein in human health and disease: a
      mystery clears up.
AB  - Tamm-Horsfall protein (THP) is exclusively produced by renal tubular cells of the
      distal loop of Henle and is the most abundant urinary protein in mammals. The
      physiological function of THP has remained elusive for over half a century;
      however, new lines of research position it as a central antimicrobial molecule
      combating urinary tract infection (UTI). Furthermore, the genetic basis of
      familial juvenile hyperuricemic nephropathy (FJHN), glomerulocystic kidney
      disease (GCKD) and autosomal dominant medullary cystic kidney disease 2 (MCKD2)
      has been recently attributed to mutations within the THP gene. In these clinical
      conditions misfolded THP accumulates in the tubular cells, ultimately leading to
      overt renal insufficiency. UTI is the most common nonepidemic bacterial infection
      in humans, where both innate and adaptive components of the immune system as well
      as the bladder epithelium are involved in its prevention and clearance. Since the
      urogenital tract is devoid of typical physical barriers such as mucus or a
      ciliated epithelium, soluble mediators with potent anti-bacterial capabilities
      might exist. Recently, genetic ablation of the THP gene was shown to lead to
      severe infection and lethal pyelonephritis in experimental models of UTI. In
      addition, mounting evidence indicates that, beyond simply a direct antimicrobial
      activity, THP is a potent immunoregulatory molecule that induces specific THP
      directed cell-mediated immunity. In light of these novel findings the particular
      role of THP as a specialized defense molecule in the urinary tract is discussed.

PMID- 15989110
TI  - Solid variant of alveolar rhabdomyosarcoma of the spermatic cord.

PMID- 15989111
TI  - Survival of "pre-viable" infants in the United States.
AB  - OBJECTIVE: We investigated temporal trend in survival of pre-viable (200-499 g)
      fetuses over the previous decade, and estimated future survival rates based on
      previous and current survival thresholds. DESIGN, SETTING AND PARTICIPANTS: This
      was a retrospective cohort study on live-born pre-viable fetuses (200-499 g) in
      the United States comparing two period cohorts; 1985-1988 versus 1995-1999. We
      computed survival of pre-viable babies (who were still alive at 24 hours) during
      the two periods and based on these results, we estimated future survival rates
      for the coming decades. MAIN OUTCOMES: Survival beyond the neonatal period.
      RESULTS: About 35 million live births were analyzed for the two periods. In the
      first period (1985-1988), 927 live births among pre-viable fetuses were recorded
      while in the second period (1995-1999) 2585 were counted, equivalent to a birth
      rate of 60.6 and 131.9 per million live births respectively. This corresponds to
      an increase of more than 100% across the decade (p for trend < 0.0001). Survival
      improved by about 50% across the period, from 12.0% to 17.4% (p < 0.0001). Based
      on these results, the survival rate among pre-viable fetuses will be expected to
      rise to about 24.0% within the next 6 years (2010). CONCLUSIONS: Survival among
      pre-viable fetuses is increasing in the United States. This raises ethical, legal
      and medical issues concerning the defined viability status of these babies, which
      is currently described as "non-viable".

PMID- 15989112
TI  - Sources of bias in reviews of spinal manipulation for back pain.
AB  - The effectiveness of spinal manipulation as a treatment for back pain remains
      uncertain and controversial. This is because of methodological weakness in many
      of the published clinical trials and also because of markedly opposing
      interpretations of the primary data by different reviewers. We have
      systematically assessed a representative sample of recent reviews on this topic.
      Reviews were included in the analysis if they were published between 1993 and
      March 2004, were listed in PubMed with an abstract and categorised as a review or
      meta-analysis, and were written in English. They were also required to present
      the evidence from at least two referenced clinical trials of spinal manipulation
      for back pain and to reach a conclusion about the effectiveness of the
      intervention. Each review was evaluated for methodological quality. Twenty-nine
      reviews met the inclusion criteria. Sixteen reached an overall positive
      conclusion, 7 a negative conclusion and 6 a neutral conclusion regarding
      therapeutic effectiveness. There were statistically significant pairwise
      correlations between each of the three factors: direction of conclusion,
      methodological quality and authorship by osteopaths or chiropracters. This
      indicates an association between authorship by osteopaths or chiropractors and
      low methodological quality and positive conclusion. We conclude that the outcomes
      of reviews of this subject are strongly influenced by both scientific rigour and
      profession of authors. The effectiveness of spinal manipulation for back pain is
      less certain than many reviews suggest; most high quality reviews reach negative
      conclusions.

PMID- 15989113
TI  - Dynamics of inflammation parameters prior to tachyarrhythmias in critically ill
      patients.
AB  - BACKGROUND: The aim of this study was to assess the dynamics of inflammation
      parameters prior to a tachyarrhythmic event in critically ill patients. We
      evaluated the course of inflammation parameters over 48 hours before the
      occurrence of tachyarrhythmias. METHODS: Prospective observational study
      conducted at a cardiologic medical-postoperative tertiary intensive care unit at
      the Vienna university hospital. Between November 1996 and July 1999 all
      consecutive patients (n = 756) were screened for the occurrence of arrhythmias.
      Patients with sustained tachyarrhythmias (n = 119) form the basis of the report.
      The tachyarrhythmia episodes were related to the evolution of C-reactive protein,
      leukocytes and fibrinogen during the 48 hours before the arrhythmic event.
      RESULTS: A total of 278 tachyarrhythmia episodes was identified (wide QRS complex
      tachycardia, n = 168; narrow QRS complex tachycardia, n = 108; ventricular
      fibrillation, n = 2). The body temperature on the day of arrhythmia was 37.4 +/-
      1 degrees C. Overall, there was no statistically significant change in any
      inflammation parameter within 48 hours prior to tachyarrhythmias (C-reactive
      protein: 17.4 +/- 12 [-48 h], 16.2 +/- 11 [-24 h], 15.2 +/- 12 [0 h] mg/dl, p =
      0.2). When stratifying for different levels of C-reactive protein on the day of
      arrhythmia, the trend was inhomogenous. For lower strata, values were
      significantly decreasing towards arrhythmias; for higher strata, an increase in C
      reactive protein was observed (stratum A: 8.5 +/- 7.2 [-48 h], 6.6 +/- 4.9 [-24
      h], 4.8 +/- 2.9 mg/dl [0 h], p = 0.0001; stratum B: 16.0 +/- 7.1 [-48 h], 13.8 +/
      6.0 [-24 h], 14.4 +/- 2.6 mg/dl [0 h], p = 0.09; stratum C: 21.2 +/- 7.4 [-48
      h], 21.5 +/- 7.5 [-24 h], 24.9 +/- 3.0 mg/dl [0 h], p = 0.008; stratum D: 34.3 +/
      13.4 [-48 h], 35.7 +/- 9.0 [-24 h], 39.7 +/- 5.5 mg/dl [0 h], p = 0.13).
      CONCLUSION: In this group of critically ill patients inflammation parameters did
      not change significantly during the 48 hours prior to the arrhythmic event. For
      different levels of C-reactive protein at the time of arrhythmia, no clear
      dynamics of inflammatory signs were observed.

PMID- 15989114
TI  - Diurnal variation of arterial stiffness and subendocardial perfusion
      noninvasively assessed using applanation tonometry in healthy young men.
AB  - BACKGROUND: Arterial stiffness is at least partially controlled by vascular tone.
      Vascular tone and underlying physiological processes, e.g. sympathetic activity,
      have been shown to follow diurnal variations. METHODS: This study investigated
      whether arterial stiffness and perfusion of subendocardial myocardium relative to
      cardiac workload show diurnal variations under physiological conditions. The
      aortic augmentation index (AIx) and subendocardial viability ratio (SEVR) were
      measured noninvasively in 26 healthy young men (27.6 +/- 3.4 years) using
      applanation tonometry at three different times (8:00, 12:00, 17:00) during one
      day. RESULTS: Mean AIx was significantly higher and mean SEVR significantly lower
      at 8:00 than at the later times. No significant differences were found between
      mean AIx and mean SEVR at 12:00 and at 17:00. CONCLUSIONS: The observed diurnal
      variations of AIx and SEVR will be of value when applanation tonometry is used in
      human research. In order to arrive at comparable data in longitudinal
      investigations, measurements should be made at similar times during the course of
      a day. In addition, our observation should assist in studies in which novel
      pharmacological compounds with activity on the vasculature are investigated.

PMID- 15989115
TI  - Enhanced plasma catecholamine and cAMP response during the head-up tilt test in
      patients with vasovagal syncope.
AB  - AIMS: Vasovagal syncope appears related to transient changes in sympathetic
      neural outflow. Several studies have documented sympathetic inhibition at the
      time of syncope. However, data on the activity of the sympathetic nervous system
      a short time before the onset of syncope are controversial. The aim of the study
      was to examine sympathoadrenal activity by measuring levels of plasma
      catecholamines and plasma cAMP in patients with vasovagal syncope induced in the
      head-up tilt test (HUT). METHODS AND RESULTS: Sixty-one syncopal patients (age 35
      +/- 15 years) underwent the passive HUT (60 degrees, 45 minutes). Blood samples
      for measurement of noradrenaline (NA), adrenaline (A) and dopamine (D) were
      obtained prior to tilt (0 minutes), at 5 minutes of tilt and at syncope or at the
      end of the HUT (45 minutes). Two samples were obtained for measurement of cAMP:
      at 0 minutes and at the end of the test. Plasma levels of NA, A and D were
      measured using high-performance liquid chromatography; plasma cAMP was measured
      using a radioimmunoassay technique. Thirty-three patients (15 men, age 35 +/- 16
      years) developed vasovagal syncope during the test (HUT-positive); twenty-eight
      patients (15 men, age 34 +/- 14 years) completed the test without syncope (HUT
      negative). No significant differences in NA, A and D were observed between the
      two groups at baseline or at 5 minutes of tilt. At the time of syncope,
      catecholamine levels in HUT-positive patients were higher than baseline levels
      (NA 428 vs. 209 pg/ml, A 90 vs. 55 pg/ml, D 297 vs. 142 pg/ml) and higher than in
      HUT-negative patients (NA 428 vs. 263 pg/ml, A 98 vs. 67 pg/ml, D 297 vs. 195
      pg/ml). cAMP levels increased at syncope and were higher than in non-syncopal
      patients at the end of the HUT (607 +/- 460 vs. 328 +/- 297 nmol/ml). CONCLUSION:
      Vasovagal syncope induced by tilt testing is associated with increased levels of
      noradrenaline, adrenaline, dopamine and cAMP. These results suggest that
      sympathoadrenal activation antecedes development of vasovagal syncope and may
      play a role in its pathophysiology.

PMID- 15989116
TI  - Motivation for therapy and the results of inpatient treatment of patients with a
      generalized anxiety disorder: a prospective study.
AB  - Whether the primary motivation for entering therapy significantly influences the
      results of inpatient psychotherapeutic treatment is subject to debate. The
      purpose of this study was to examine this question in women with generalized
      anxiety disorder. The monitored results from 54 female inpatients (29 who were
      highly motivated to enter therapy and 25 who were minimally motivated) were
      compared. The questionnaire for measuring psychotherapy motivation (FMP), the
      symptom checklist (SCL-90-R) and the questionnaire for measuring change of
      experience and behavior (VEV) were used to assess motivation and results of
      treatment. The patients were tested at admission and after the fourth and sixth
      weeks of therapy, at which time the patients with high primary motivation showed
      a significantly more marked reduction of anxiety symptoms (SCL-90-R, P < 0.01).
      These patients also had better test results on the VEV (P < 0.01). However, both
      quantitative and qualitative improvements in motivation for therapy were observed
      among the less motivated patients, and this improvement did not differ from that
      of the highly motivated group on most scales of the FMP (P < 0.05 to P = 0.43).
      Highly motivated patients with generalized anxiety disorder can profit
      significantly more from inpatient psychosomatic treatment than those who have
      less primary motivation. However, less motivated patients can show significant
      positive changes in developing motivation for therapy, as well as in the final
      results of treatment. Establishing and developing motivation prior to
      hospitalization might contribute to more efficient and cost-effective clinical
      treatment.

PMID- 15989117
TI  - Phlegmonous gastritis in a patient with rheumatoid arthritis.
AB  - Phlegmonous gastritis is an acute infection of the stomach wall by pyogenic
      bacteria. It represents an extremely rare disease with a fulminating course and a
      high mortality rate. A precise lifetime diagnosis is generally unsuccessful. The
      inflammation, most often caused by alpha-hemolytic streptococci, is most
      frequently expressed in patients who are more susceptible to infection. Among
      these are elderly patients, women, patients with chronic gastritis, chronic
      peptic ulcer, hepatic cirrhosis and decreased immune tolerance, T-cell leukemia,
      patients with a low socio-economic status and alcoholics. In our paper we are
      describing the case of a 66-year old female patient, who had received many years
      of treatment for rheumatoid arthritis. She died due to phlegmonous gastritis,
      which was only established post-mortem. The authors share the opinion that the
      occurrence of the phlegmonous form of gastritis was influenced significantly by
      the treatment with nonsteroidal antirheumatics and corticosteroids, which she had
      received for many years and also immediately prior to the complication.

PMID- 15989118
TI  - [Leopards, lions and wolves--a short visit to the zoo of dermatological
      diagnoses].

PMID- 15989119
TI  - Experimentally manipulating the effects of involuntary conscious memory on a
      priming task.
AB  - Recent studies showed that involuntary conscious memory can enhance priming in
      implicit tasks. However, because the results of these studies were based on post
      hoc selection methods in which subjects were assigned to conditions (aware or
      unaware) based on their responses on a posttest questionnaire, it is possible
      that subject selection effects may have influenced the results. The present study
      used a novel method that experimentally manipulated the effects of involuntary
      conscious memory on a word stem task. This was accomplished by inducing the
      experience of word recollection in one test condition while inhibiting it in
      another. This study showed that subjects who experienced word recollection showed
      significantly higher rates of priming than those who did not. The results
      represent the first purely experimental demonstration of involuntary conscious
      memory's ability to affect priming on implicit tasks.

PMID- 15989120
TI  - Unconscious perception or not? An evaluation of detection and discrimination as
      indicators of awareness.
AB  - Most investigations of unconscious perception use a dissociation design in which
      an awareness variable (e.g., detection) is compared with a perceptual processing
      variable (e.g., identification). Unconscious perception is inferred when the
      awareness variable lacks sensitivity to the stimulus but evidence of perceptual
      processing is still obtained. In two studies we examined the relationship between
      word identification and detection (Study 1) or discrimination (words vs.
      nonwords; Study 2) with a variety of techniques. In both studies, dissociations
      suggestive of unconscious perception occurred when the data were examined with
      subjective threshold approaches, but these differences disappeared when the
      variables were compared with techniques derived from signal detection theory
      (SDT). These results do not support unconscious perception in subjective
      threshold paradigms. In addition, detection appears to be the most sensitive and
      appropriate task for assessing stimulus awareness, provided that several SDT
      assumptions are met.

PMID- 15989121
TI  - The cognitive interview: does it successfully avoid the dangers of forensic
      hypnosis?
AB  - Seventy-two undergraduates viewed a videotape of a bank robbery that culminated
      in the shooting of a young boy. Several days later, participants were interviewed
      about their recollection of events in the film through baseline oral and written
      narrative accounts followed by random assignment to a hypnosis (HYP) condition,
      the cognitive interview (CI), or a motivated, repeated recall (MRR) control
      interview. Participants also completed a forced interrogatory recall test, which
      indexed potential report criterion differences between the interview conditions.
      In terms of information provided for the first time during treatment interviews,
      HYP led to greater productivity than the CI or the MRR interview, which did not
      differ significantly from each other. Evidence that these differences in recall
      resulted primarily from report criterion differences rather than differences in
      accessible memory was obtained from the forced interrogatory recall test. In this
      test, no differences were observed between the three interview conditions.
      Finally, the data revealed that participants' hypnotic ability was associated
      with the recall of erroneous and confabulatory material for those tested in the
      HYP and CI conditions but not those in the MRR condition. This suggests that some
      CI mnemonics may invoke hypnotic-like processes in hypnotizable people.

PMID- 15989122
TI  - The nature of memory errors for verbally quantified information.
AB  - A variety of theoretical proposals claim that memory is not a faithful
      reproduction of what was encountered but a blend of what was encountered and
      knowledge from other sources. We showed participants simple pairings of a
      person's name and a height or weight or a food name and a calorie count at study.
      Once veridical responses were removed, there was little evidence that the
      remaining responses were influenced by the specific value of the studied
      stimulus. These results suggest that the appearance of memory blends for verbally
      quantified information may be induced by averaging over different knowledge
      states.

PMID- 15989123
TI  - Is the worldview of qualitative inquiry a proper guide for psychological
      research?
AB  - Qualitative methods are becoming increasingly popular in psychology. Although the
      distinction between qualitative and quantitative often is stated in terms of
      methods, the real distinction is between worldviews: that favored by most
      qualitative methodologists, which emphasizes subjective experience and multiple
      realities, and that commonly accepted in science. The worldview accepted by most
      adherents of qualitative inquiry suggests the exclusive use of methods that
      include verbal reports of lived experience. Qualitative methods serve an
      important function in psychology, but their use as recommended by their adherents
      is limited in 2 respects: The adherents use a narrow and unconventional approach
      to qualitative methods that differs from that normally understood, and they favor
      use of a restricted range of qualitative methods over other qualitative methods
      and quantitative methods. If qualitative inquiry is to make a greater
      contribution to psychology, researchers in that tradition must acquire a better
      understanding of contemporary science, correct their misunderstandings of the
      rationale for quantitative methods, and address the apparent limitations of their
      methods emphasizing reported experience.

PMID- 15989124
TI  - What didTriplett really find? A contemporary analysis of the first experiment in
      social psychology.
AB  - In 1898, Norman Triplett published was has been called the first experiment in
      social psychology and sports psychology. Claiming to demonstrate "the dynamogenic
      factors in pacemaking and competition," this oft-cited article began the serious
      investigation of social facilitation. This area of research now numbers in the
      hundreds of published works, includes the study of humans and other animials, and
      encompasses basic research and applied settings. But what did Triplett really
      find? I examine Triplett's original data and show that very little evidence
      existed for the social facilitation of the simple task he investigated. These
      analyses indicate the need to correct contemporary accounts of Triplett's work
      and underscore the differences in how research was evaluated at that time
      compared with today.

PMID- 15989125
TI  - [Standards for weaning smokers].

PMID- 15989127
TI  - Influence of naturally acquired feline leukemia virus (FeLV) infection on the
      phagocytic and respiratory burst activity of neutrophils and monocytes of
      peripheral blood.
AB  - The purpose of this study was cytometric evaluation of phagocytic and oxidative
      burst activity of neutrophils and monocytes in cats naturally infected with FeLV.
      To conduct the study, the peripheral blood was obtained from 33 cats naturally
      infected with FeLV. The control group consisted of 30 FeLV-, FIV-, clinically
      healthy cats. The percentage of phagocytizing neutrophils of peripheral blood was
      lower in FeLV+ than in FeLV- cats. The percentage of neutrophils and monocytes in
      which an oxidative burst occurred was lower in FeLV+ than in FeLV-animals. Also
      an oxidative product formation in neutrophils after E. coli and PMA stimulation
      was lower in FeLV+ than in FeLV-animals. Obtained results allow to conclude that
      diminished phagocytic and oxidative burst activity of peripheral blood leukocytes
      may cause impairment of innate immunity in cats infected with FeLV.

PMID- 15989126
TI  - The effect of intramuscular injections of boar pheromone 5alpha-androstenol on
      the hormonal regulation of the estrous cycle in hypoosmatic gilts.
AB  - Until 1999 it was accepted that pheromones act exclusively by stimulating the
      dendritic receptors present in olfactory epithelium. Cycling gilts with an
      experimentally-disrupted neural olfactory pathway were used to test the
      hypothesis that boar pheromone 5alpha-androstenol may affect the secretion of
      hormones involved in the regulation of the estrous cycle by the humoral pathway.
      On day 12 of the estrous cycle the nasal cavity of gilts (n=15) was irrigated
      with zink sulfate solution. From day 16 to 20, the experimental group (n=10) was
      injected intramuscularly with 5alpha-androstenol (20 microg) twice a day. Blood
      samples were collected from the jugular vein at 4 h intervals on days 17-21 to
      estimate plasma concentration of LH, oxytocin, estradiol-17beta, testosterone and
      progesterone. The experimental group displayed a significantly lower mean
      concentration of LH than the control animals (P<0.0001). The decrease in
      concentration of LH was accompanied by the reduction of oxytocin (P<0.001),
      estradiol-17beta (P<0.001) and testosterone (P<0.01) secretion. These results
      demonstrated that 5alpha-androstenol influenced hormonal regulation by humoral
      pathway and might be considered to be the priming pheromone in gilts.

PMID- 15989128
TI  - Effect of leukotoxin of Mannheimia haemolytica and LPS of E. coli on secretory
      response of bovine neutrophils in vitro.
AB  - To evaluate the role of leukotoxin (LKT) of Mannheimia haemolytica and
      lipopolysaccharide (LPS) of E. coli 055:B5 in pathogenesis of bovine respiratory
      disease (BRD) we investigated their in vitro effects on cultured bovine
      neutrophils. Functional parameters of neutrophils including degranulation,
      generation of superoxide, and nitric oxide were distorted in response to both
      toxins. The most essential reaction of neutrophils was found in respect to
      release of elastase after addition of LKT as well as LPS at concentration of 300
      microg/ml. Moreover, we observed an increased release of myeloperoxidase (MPO)
      and alkaline phosphatase (ALK-P) from polymorphonuclear cells (PMN) after
      addition of LKT and LPS. We also found enhanced superoxide generation by bovine
      neutrophils after exposure to different concentrations of LKT and LPS. In
      cultures of PMN treated with LKT, concentration of nitrite increased with growing
      concentrations of LKT. Lower values of nitrite were obtained in cultures exposed
      to LPS. Partial lysis of PMN, determined by LDH (lactate dehydrogenase) leakage,
      started at concentration of 300 microg/ml for both toxins, meanwhile LKT
      concentration above 300 microg/ml was lethal. Our study has revealed that
      neutrophils in response to both toxins exaggerate release of analysed substances,
      which participate in worsening the course of the disease and play a role in lung
      injury during BRD. Toxins introduced to the cultural medium stimulate release of
      studied constituents from neutrophils by combined activation and lysis of
      neutrophils.

PMID- 15989129
TI  - Values of selected immune and haematological parameters in healthy rabbits.
AB  - In the paper, values of selected indices of non-specific immunity as well as
      white and redblood cell patterns were presented in healthy rabbits at the age of
      3 to 4,5 months. The purpose of the study was to provide reference values in
      healthy rabbits being frequent research model in the studies of several diseases
      in humans and animals.

PMID- 15989130
TI  - Influence of progesterone, pregnenolone and 17beta-hydroxyprogesterone on the
      function of bovine luteal cells treated with luteinizing hormone, noradrenaline
      and prostaglandin E2.
AB  - The aim of the present study was to investigate the influence of progesterone
      (P4), its precursor (pregnenolone; P5) and metabolite (17beta
      hydroksyprogesterone; 17betaOHP4) on secretory function of bovine luteal cells on
      days 6-10 of the estrous cycle and on intracellular Ca2+ mobilization. The luteal
      cells were pre-incubated for 24 h and after change of medium they were incubated
      for 30 min with P5 and 17betaOHP4 (10(-5) each). Next, the medium was
      supplemented with LH (100 ng/ml), noradrenaline (NA; 10(-5) M) and prostaglandin
      (PG)E2 (10(-6) M), the cells were incubated for further 4 h and the medium was
      collected for P4 determination. Another set of luteal cells (5x10(4)/well) was
      incubated with P4, P5 and 17betaOHP4 at the dose of 10(-5) M each for 30 min and
      intracellular Ca2+ mobilization was measured every 5 s three times before and for
      60 s after cells stimulation with LH, NA and PGE2. Metabolite of P4 did not
      affect the stimulatory effect of LH, PGE2 and NA on P4 secretion to the medium.
      Whereas all used steroids reduced calcium release from small but not from large
      luteal cells. It is suggested that steroids could temporary impair effect of
      luteotropins on the luteal cells via non-genomic way.

PMID- 15989131
TI  - Concentration of ascorbic acid in the blood of cows with subclinical mastitis.
AB  - The aim of the investigations was evaluation of ascorbic acia concentration in
      the blood or cows in the subclinical form of mastitis. The research was conducted
      on 56 cows. The cows were divided into 4 groups: A, B, and C with subclinical
      form of mastitis caused by Staphylococcus aureus, Streptococcus agalactiae and
      Escherichia col, and D control. The ascorbic acid concentration in the serum of
      cows was measured by the hydrazine method. We observed a marked decrease in
      ascorbic acid concentration in the serum of cows from experimental groups A, B
      and C, respectively: 34.2, 35.9, and 39.4 micromol/dm3 when we compared them with
      control group D--69.8 micromol/dm3. In cows with subclinical form of inflammation
      of the mammary gland, a decreased potential of antioxidant protection in the
      blood was noticed, which manifested itself as a lower ascorbic acid
      concentration.

PMID- 15989132
TI  - Studies on nucleolar organiser regions (AgNors) in selected spontaneous and
      transplantable animal tumors.
AB  - Behaviour of argyrophilic nucleolus organising regions (AgNOR) was estimated in
      various types of spontaneous and transplantable tumors in animals. The studies
      were performed on spontaneous epithelial and mesenchymal tumors, malignant and
      non-malignant, as well as transplantable tumors: Morris hepatoma, mammary gland
      carcinoma and Yoshid sarcoma. The examinations were made on paraffin sections,
      using silver-staining method according to Ploton et al. Quantitative assessment
      was made with computer-aided microscopic image analysis system Multi-Scan Base
      V.8 for Windows, coupled with Carl Zeiss microscope. It was demonstrated that
      AgNOR index reflects malignancy of the tumor, since it increases clearly in
      cancers and sarcomas, both spontaneous and transplantable. The highest AgNOR
      index--0.13--was noted in the group of spontaneous tumors in epithelial malignant
      tumors, and in the group of transplantable tumors in mesenchymal tumors (Yoshid
      sarcoma) it was 0.15. Classification of the studied spontaneous and
      transplantable tumors into groups of the same histogenesis, though phenotypically
      different, was aimed at demonstration of the increasing tendency of AgNOR index.

PMID- 15989134
TI  - Prevalence of the suilysin gene in Streptococcus suis strains isolated from
      diseased and healthy carrier pigs.
AB  - Knowledge of virulence factors of Streptococcus suis is limited. Several
      virulence factor candidates have been proposed, among them suilysin, which is
      responsible for a toxic effect on epithelial cells. The aim of this study was to
      detect the suilysin gene sequence in Streptococcus suis strains of various
      origin. In total 63 Streptococcus suis isolates were investigated. Forty four of
      them originated from tissues of streptococcosis affected animals. The remaining
      19 strains were isolated from tonsils of healthy carrier pigs. Suilysin gene
      specific sequence was detected in 79% of the strains tested. In isolates obtained
      from pigs with signs of streptococcosis this gene sequence was recorded in 85% of
      cases. In Streptococcus suis strains isolated from healthy carrier pigs the
      suilysin gene was detected in 63% of the isolates. It seems that suilysin toxic
      activity is only one of the many steps involved in the pathogenesis of
      Streptococcus suis infection and that strain's virulence cannot be stated only on
      the basis of suilysin gene sequence presence.

PMID- 15989133
TI  - Comparison of some serological methods and coproscopic examinations for diagnosis
      of Giardia spp. invasion in dogs.
AB  - Giardiasis was detected in 53.5% of dogs examined by FASTest Giardia Strip for
      use in dogs. Using the ProSpecT Giardia EZ Microplate Assay 52.2% of these
      results was confirmed. Cysts of Giardia spp. were found only in 6.5% of samples
      of feces examined by flotation or decantation techniques. The examinations
      confirmed problems with coproscopic diagnosis of giardiasis in dogs. They
      confirmed the greater usefulness of FASTest Giardia Strip for immunodiagnostic of
      giardiasis in carnivores.

PMID- 15989135
TI  - Laparoscopic removal of gastric foreign bodies in dogs--comparison of manual
      suturing and stapling viscerosynthesis.
AB  - This study was an attempt to evaluate the application of various laparoscopic
      techniques of removing foreign bodies from the stomach in dogs in comparison to
      conventional laparotomy. The research was conducted on two groups of 10 dogs each
      with clinically confirmed foreign bodies in the stomach. In case of all patients,
      a laparoscopic instrument, EndoBag, was used for the removal of the foreign body
      from the stomach and the abdominal cavity. Manual suturing with the use of Szabo
      Berci suturing kit was used for the gastrotomy wound closure in group I. In group
      II, linear staplers were used for viscerosynthesis. All patients were subjected
      to radiological assessment of tightness of anastomosis. No significant
      differences between the quality of the performed stomach anastomosis were shown.
      Therefore, the competitiveness of an economical manual suturing in comparison
      with the very expensive mechanical suturing preferred in human surgery was
      confirmed. The described procedures of laparoscopic gastrotomy seem to be
      applicable for removing foreign bodies from the stomach in a clinical veterinary
      practice.

PMID- 15989136
TI  - The influence of experimental ileitis on the neuropeptide coding of enteric
      neurons in the pig.
AB  - In the present study, both the ELISA test and immunohistochemical staining were
      used to investigate the influence of artificially induced ileitis on the chemical
      coding of enteric neurons in the pig. The ileum wall in experimental (E) pigs was
      injected in multiple sites with 4% paraformaldehyde to induce inflammation, while
      in the control (C) animals, the organ was injected with 0.1M phosphate buffer (pH
      7.4). Three days after ileitis induction, samples of ileum wall from all the
      animals were evaluated for VIP, SP, CGRP, NPY, GAL and SOM concentration (ELISA
      test) and the expression of these biologically active substances by the enteric
      neurons (immunohistochemical staining). Quantitative results showed that ileitis
      decreased tissue concentration of VIP, CGRP and SOM but increased tissue
      concentration of SP, NPY and GAL. Immunochemistry revealed that in both the
      experimental and control pigs, VIP-positive (VIP+) nerve fibers supplied mainly
      ileal blood vessels, and the labeled pericarya were located in the inner (ISP)
      and outer submucous plexus (OSP). SP+ and CGRP+ nerve terminals were found in
      both the mucous and muscular membrane, while the labeled pericarya were found in
      ISP, OSP and myenteric plexus (MP). In both C and E pigs, the very few nerve
      terminals containing NPY and SOM were located mainly in the mucous membrane. NPY-
      or/and SOM-immunopositive nerve cell bodies were found in ISP, OSP and MP. GAL+
      nerve fibers supplied all layers of the ileum and were most numerous in the
      muscular membrane, while the labeled pericarya were present in all the enteric
      plexuses. The present results suggest that enteric neurons are highly plastic in
      their response to inflammation.

PMID- 15989137
TI  - Perineal hernia in 3 cats.
AB  - Cases of perineal hernias in three cats are described. All the cats were male (2
      castrated, 1 intact). The hernias were situated between the external anal
      sphincter and the levator ani muscle. The hernial sac contained a dilated rectum
      filled with fecal content (2 cats) as well as a small amount of retroperitoneal
      fatty tissue (2 cats) and urinary bladder (1 cat). A standard perineal
      herniorrhaphy in two cats, and herniorrhaphy via elevation of the internal
      obturator muscle in one cat were performed. No recurrence of the problem was
      observed in two cats during 9 months following the surgery. In one case, mild
      stretching of the pelvic diaphragm was noted with sporadic mild defecation
      problems observed after a 12-month period.

PMID- 15989138
TI  - Treatment of chronic complete rupture of achilles tendon in three dogs with
      locking loop suture and own suture technique.
AB  - The present case report describes three heavy dogs, Caucasian Shepherd breed,
      with chronic complete traumatic rupture of Achilles tendon, which was repaired
      with two types of sutures. Surgical treatment involved shortening the Achilles
      tendon, and using a locking loop suture technique and own suture technique with
      four buttons. Additionally, positional screw and cast supported the sutures.
      Twelve months postoperatively no discomfort and lameness were observed on
      clinical examination. This paper shows that treatment of chronic complete rupture
      of Achilles tendon with locking loop suture and own suture technique gives good
      results.

PMID- 15989139
TI  - Vinyl chloride-a classical industrial toxicant of new interest.
AB  - The carcinogenicity of vinyl chloride in humans was recognized in 1974 based on
      observations of hepatic angiosarcomas in highly exposed workers. A multiplicity
      of endpoints has been demonstrated. The primary target organ, the liver, displays
      differential susceptibilities of hepatocytes and sinusoidal cells, which are
      modified by factors of age and dose. There is consistency in organotropism
      between experimental animals and humans. Vinyl chloride is a pluripotent
      carcinogen, predominantly directed toward hepatic endothelial (sinusoidal) cells,
      and second toward the parenchymal cells of the liver. The similarity of results
      between experimental animals and humans is a solid basis of an amalgamation of
      experimental and epidemiological risk estimates. Vinyl chloride requires
      metabolic activation for carcinogenicity and mutagenicity, and toxicokinetics are
      a key to interpret the dose response. Practically the entire initial metabolism
      of vinyl chloride is oxidative. At higher exposure concentrations this is
      nonlinear, and metabolic saturation of metabolism in rats is reached at about 250
      ppm. This is consistent with the plateau of hepatic angiosarcoma incidence in rat
      bioassays. Physiologically based pharmacokinetic/toxicokinetic (PBPK) models have
      been developed and successfully applied within the frame of human cancer risk
      assessments. The major DNA adduct induced by vinyl chloride (approximately 98% of
      total adducts in rats), 7-(2-oxoethyl)guanine, is almost devoid of promutagenic
      activity. The clearly promutagenic "etheno" adducts N2,3-ethenoguanine and 3,N4
      ethenocytosine each represent approximately 1% of the vinyl chloride DNA adducts
      in rats, and 1,N6-ethenoadenine is found at even lower concentrations. Etheno
      adducts appear to have a long persistence and are repaired by glycosylases. Vinyl
      chloride represents a human carcinogen for which a series of mechanistic events
      connects exposure with the carcinogenic outcome. These include (1) metabolic
      activation (to form chloroethylene oxide), (2) DNA binding of the reactive
      metabolite (to exocyclic etheno adducts), (3) promutagenicity of these adducts,
      and (4) effects of such mutations on protooncogenes/tumor suppressor genes at the
      gene and gene product levels. In rat hepatocytes, a further event is a biomarker
      response. Cancer prestages (enzyme-altered foci), as quantitative biomarkers,
      provide a tool to study dose response even within low dose ranges where a
      carcinogenic risk cannot be seen in cancer bioassays directly. Such biomarker
      responses support a linear nonthreshold extrapolation for low-dose assessment of
      carcinogenic risks due to vinyl chloride. Published risk estimates based on
      different sets of data (animal experiments, epidemiological studies) appear
      basically consistent, and on this basis an angiosarcoma risk of approximately 3 x
      10(-4) has been deduced by extrapolation, for exposure to 1 ppm vinyl chloride
      over an entire human working lifetime. An important point that should be
      considered in regulatory standard settings is the presence of a physiological
      background of those etheno DNA adducts, which are also produced by vinyl
      chloride. Likely reasons for this background are oxidative stress and lipid
      peroxidation. In essence, fundamentals of the hepatocarcinogenicity of vinyl
      chloride appear now well established, providing a solid scientific basis for
      regulatory activities.

PMID- 15989140
TI  - Role of metabolism in drug-induced idiosyncratic hepatotoxicity.
AB  - Rare adverse reactions to drugs that are of unknown etiology, or idiosyncratic
      reactions, can produce severe medical complications or even death in patients.
      Current hypotheses suggest that metabolic activation of a drug to a reactive
      intermediate is a necessary, yet insufficient, step in the generation of an
      idiosyncratic reaction. We review evidence for this hypothesis with drugs that
      are associated with hepatotoxicity, one of the most common types of idiosyncratic
      reactions in humans. We identified 21 drugs that have either been withdrawn from
      the U.S. market due to hepatotoxicity or have a black box warning for
      hepatotoxicity. Evidence for the formation of reactive metabolites was found for
      5 out of 6 drugs that were withdrawn, and 8 out of 15 drugs that have black box
      warnings. For the other drugs, either evidence was not available or suitable
      studies have not been carried out. We also review evidence for reactive
      intermediate formation from a number of additional drugs that have been
      associated with idiosyncratic hepatotoxicity but do not have black box warnings.
      Finally, we consider the potential role that high dosages may play in these
      adverse reactions.

PMID- 15989142
TI  - Look what's next in telemedicine: the physician assistant and telemedicine.

PMID- 15989141
TI  - Differential effects of histone deacetylase inhibitors in tumor and normal cells
      what is the toxicological relevance?
AB  - Histone deacetylase (HDAC) inhibitors target key steps of tumor development: They
      inhibit proliferation, induce differentiation and/or apoptosis, and exhibit
      potent antimetastatic and antiangiogenic properties in transformed cells in vitro
      and in vivo. Preliminary studies in animal models have revealed a relatively high
      tumor selectivity of HDAC inhibitors, strenghtening their promising potential in
      cancer chemotherapy. Until now, preclinical in vitro research has almost
      exclusively been performed in cancer cell lines and oncogene-transformed cells.
      However, as cell proliferation and apoptosis are essential for normal tissue and
      organ homeostasis, it is important to investigate how HDAC inhibitors influence
      the regulation of and interplay between proliferation, differentiation, and
      apoptosis in primary cells as well. This review highlights the discrepancies in
      molecular events triggered by trichostatin A, the reference compound of
      hydroxamic acid-containing HDAC inhibitors, in hepatoma cells and primary
      hepatocytes (which are key targets for drug-induced toxicity). The implications
      of these differential outcomes in both cell types are discussed with respect to
      both toxicology and drug development. In view of the future use of HDAC
      inhibitors as cytostatic drugs, it is highly recommended to include both tumor
      cells and their healthy counterparts in preclinical developmental studies.
      Screening the toxicological properties of compounds early in their development
      process, using a battery of different cell types, will enable researchers to
      discard those compounds bearing undesirable adverse activity before entering into
      expensive clinical trials. This will not only reduce the risk for harmful
      exposure of patients but also save time and money.

PMID- 15989143
TI  - Community-acquired Escherichia coli meningitis in adult.
AB  - We report a case of E. coli meningitis presented initially without nuchal
      rigidity. Despite intensive care treatment, CSF was not sterilized and the
      patient died at 17 days after his admission. Patients with an unexplained altered
      sensorium with fever should undergo LP to evaluate for this rare entity and to
      direct early antimicrobial treatment which possesses efficacy for meningeal
      infection.

PMID- 15989144
TI  - Improved hypercalcemia after debulking of uremic tumoral calcinosis in a
      parathyroidectomized patient.
AB  - Uremic Tumoral Calcinosis (UTC) is a rare complication of chronic kidney disease
      on dialysis, characterized by large periarticular calcification. Among some
      cases, hypercalcemia with no conventional etiologies has been reported. We
      present a case of UTC in which hypercalcemia occurred after parathyroidectomy and
      introduction of low-calcium containing dialysate. Work-up of hypercalcemia did
      not reveal any conventional etiology, but hypercalcemia resolved after debulking
      of the tumor. This change in serum calcium gives us an insight into the mechanism
      of hypercalcemia, occasionally seen among cases with UTC.

PMID- 15989145
TI  - The Clinical Research Center of Hawaii: a nine year progress report.
AB  - The UH-CRC is an NIH minority funded infrastructure program at the University of
      Hawaii in partnership with Hawaii Pacific Health, now in its ninth year. The main
      purpose of the UH-CRC is to foster clinical research at UH in order to improve
      the health of the citizens of Hawaii, particularly those who suffer
      disproportionately from disorders affecting these communities. This status report
      documents the continued success and progress of the Center Manuscripts published
      or in press have increased from an average of 43 in years 1-3 to 54 in years 4-6
      to 84 for years 7-9. Actual dollars received per year ranged from 1-7 million
      dollars the first 6 years, but reached 8-22 million dollars the last three years.
      This status report also documents the mandate for this clinical research
      infrastructure program to compete successfully for mainstream funding status by
      2010.

PMID- 15989146
TI  - Medical school hotline: clinical faculty at JABSOM.

PMID- 15989147
TI  - Cancer research center hotline: complement depletion: use of human C3/cobra venom
      factor (CVF) chimeric proteins as therapeutic agents.

PMID- 15989148
TI  - Resources for editors and editorial board members.

PMID- 15989149
TI  - Tips for success: matching journals and topics.

PMID- 15989151
TI  - Plagiarism.

PMID- 15989152
TI  - Genomics and public health.

PMID- 15989153
TI  - Paradox of vitamin A supplementation to children in India.

PMID- 15989154
TI  - Prevalence of disability and handicaps in geriatric population in rural south
      India.
AB  - Proportion of aged persons in India is increasing and is expected to be around 70
      million by the end of the year 2000. The epidemiological consequences would be
      increase in the geriatric problems, particularly, impairments, disabilities and
      handicaps There are not many community-based studies using the International
      Classification of Impairments, Disabilities and Handicaps (ICIDH). The main
      objective of this study was to estimate the prevalence of disabled in the elderly
      population (aged above 60 years) in a district of south India using ICIDH
      classification. Thirty villages were selected using probability proportional to
      size linear systematic sampling (PPSLSS) from Villupuram health unit district in
      Tamilnadu in south India. One hundred and five households were selected from each
      selected village by using linear systematic sampling. A structured proforma was
      administered to 974 subjects to obtain information on disability as perceived by
      rural geriatric population. Visual disability was found to be the most important
      single preventable disability (56%). Only 33% of persons with visual disability
      wore spectacles. A decline in social interaction was reported. There was an
      urgent need to strengthen health care activities related to geriatric health care
      to improve the quality of life of the elderly population, including care of
      vision in particular.

PMID- 15989155
TI  - Nutritional status of adolescent girls in a rural area of North 24 Parganas
      district, West Bengal.
AB  - A community based, cross-sectional study was conducted during June to December
      1999 in Amdanga block of North 24 Parganas district, West Bengal. Among a sample
      of 143 adolescent girls (10-19 years), selected through multistage sampling
      procedure. Data was collected by interviewing the adolescent girls and their
      parent, whenever necessary using pre-designed, pre-tested, semi-structured
      schedule. Anthropometric measurements were recorded using standardized
      methodology as recommended by WHO and standard clinical examination procedures
      were followed. Standard operational definitions were used. Appropriate
      statistical tests like Chi-square test were applied as and when required. Overall
      prevalence of 'thinness' and 'stunting' were found to be 14.7% and 37.8%
      respectively. There was no significant association (p > 0.05) of thinness or
      stunting with per capita monthly family income and literacy status of parents.
      Common nutritional deficiency disorders were anaemia (44.8%), dental caries
      (25.9%), angular stomatitis (15.4%) etc.

PMID- 15989156
TI  - Sero-positivity of brucellosis in human beings.
AB  - Two hundred and fifty human serum samples were collected (122 from general
      population and the rest from people associated with animals) from central Kerala
      and tested for Brucella agglutinins using various standard tests. The overall
      seropositivity for brucellosis using all the tests was 1.6%. Among the general
      population a prevalence of 2.45% was observed and among the veterinary students
      1.14%.

PMID- 15989157
TI  - Epidemiological aspects of acute childhood poisoning among patients attending a
      hospital at Kolkata.
AB  - A retrospective study from a tertiary care teaching hospital in Kolkata revealed
      3.6% of total paediatric admissions were due to poisoning. Majority of the cases
      included oral/chemical poisoning followed by biological/envennomation. Kerosene
      was the commonest among all poisoning. Most of the cases were accidental.

PMID- 15989158
TI  - Mother's use of medication in their children of preschool age.
AB  - Self medication by mothers influences the morbidity and mortality in children.
      The present study evaluates mothers' attitude and practices regarding use of
      medication in their preschool age children. 976 mothers having at least one child
      <6 years with history of illness in past 30 days were interviewed according to a
      predesigned questionnaire. Five hundred and seventy five (58.91%) used medication
      on their own, most commonly for cough & cold (23.9%). The commonest nonprescribed
      drugs used were analgesics--antipyretics (34.9%). Inspite of the nonresponse,
      shortage of money and availability of the drugs without prescription has
      encouraged self medication. These findings necessitates mothers' education and
      enforcement of law against selling of non-prescribed drugs.

PMID- 15989159
TI  - Knowledge and attitude of males regarding birth spacing and contraception.
AB  - A cross sectional study with 368 males (husbands of women delivered at Regional
      Institute of Medical Sciences hospital) revealed that 89% of them were aware of
      contraception. But only the meaning of birth spacing was known to 13% of them
      correctly. Education, income and parity were significantly associated with
      knowledge on birth spacing.

PMID- 15989160
TI  - Awareness of HIV/AIDS among medical students.
AB  - A cross-sectional study among 145 fresh entrants of medical education revealed
      that, 99% of boys and 98% of girls are aware of AIDS by its definition and its
      causation. 96% of girls, compared to 91% of boys are aware that, HIV spreads by
      blood. Very few, 5% of girls and 2.5% of boys are of the misconception that HIV
      may be transmitted through health personnel on examination of HIV patient. About
      80% of boys and 90% of girls opine that HIV is transmitted through pregnancy.

PMID- 15989161
TI  - A study of compliance status of diabetes mellitus patients.
AB  - A clinic based descriptive (case series) study was conducted among 106 study
      subjects with poor glycaemic control in a tertiary care hospital, Kolkata. Poor
      compliance was observed in 89.62% and 10.38% had good/acceptable compliance.
      Compliance was better in above 60 years age group, in males, in married and
      educated persons. Non-compliance factors acted mostly in combination.

PMID- 15989162
TI  - Spring and fall seem to be the "seasons" of conferences.

PMID- 15989163
TI  - The power of narratives.

PMID- 15989164
TI  - Global biological threats to health: an imperative for collaboration.
AB  - Biological threats to health are challenging governments worldwide. National
      strategies for preventing and managing existing and emerging threats require
      significant collaboration across borders, sectors, services, agencies and
      professions. Perhaps most important are the partnerships of key national health
      leaders who can develop and foster these relationships. Government Chief Nursing
      Officers (CNOs) and Chief Medical Officers (CMOs), providing leadership in more
      than 100 countries worldwide, play crucial roles in addressing biological threats
      to health. However, much of this leadership is exercised without the benefit of
      strong collaborative relationships between these two key national leaders.
      Unfortunately, without functional partnerships between nurses and physicians at
      all levels, national and global capacity to address biological and other threats
      will be greatly compromised. For these reasons, the first ever global forum for
      CNOs and CMOs teams was hosted by the Lillian Carter Center for International
      Nursing in Atlanta, in June 2004. Representatives from 70 countries focused on
      biological threats in relation to three key purposes: (1) gaining shared
      scientific and practical knowledge; (2) developing and strengthening
      collaboration and partnerships among CNOs and CMOs; and, (3) creating a joint
      plan for advancing national preparedness. This article describes the content,
      process and outcomes of this historic meeting.

PMID- 15989165
TI  - Tobacco control in the 21st century: a critical issue for the nursing profession.
AB  - Tobacco control is central to reducing death and disability and improving quality
      of life worldwide and nursing action is imperative. This article addresses
      tobacco as a global health issue with implications for nursing practice,
      education, research, and policy development. The lack of knowledge and skills,
      lack of expectation for clinical intervention, limited research, an absence of
      professional policies, and minimal nursing leadership have diminished the
      critical role that nurses can play in confronting this epidemic. Swift action is
      needed to ensure that all nurses are prepared to effectively engage in activities
      to prevent tobacco use, provide evidence-based cessation interventions, and
      support efforts to prevent exposure to secondhand smoke. Increased opportunities
      are needed to support creative nursing research efforts that test interventions
      and strategies to reduce barriers to tobacco control within different cultures,
      subcultures, and countries.

PMID- 15989166
TI  - Synthesis of intervention research to modify physical activity and dietary
      behaviors.
AB  - A descriptive literature review was conducted to examine conceptual and
      methodological issues of interventions aimed at improving both physical activity
      and diet behaviors according to critical elements established by Sidani and
      Braden (1998). The method of the review of 30 articles describing 17 intervention
      studies focused on the following nine elements: (a) relevance of the intervention
      to the targeted outcome; (b) theoretical components of the intervention; (c)
      intervention components; (d) complexity, strength, and integrity of the
      intervention; (e) extraneous factors; (f) adherence to the intervention and
      retention; (g) reliability and validity of the outcome measures; (h) expected
      outcomes; and (i) effectiveness of the intervention. The results were that the
      interventions were relevant and included multiple components, but most
      interventions lacked an explicit theoretical framework. Adherence to the
      intervention and retention were problems. Overall, to varying degrees and for
      those completing the programs, the interventions were effective for increasing
      physical activity, lowering dietary fat, weight loss, and reducing risk for
      illness. Twelve "lessons learned" evolved that have practical and research
      implications. One salient lesson and future priority is to incorporate theory to
      reveal the intervention content and mechanisms to modify physical activity and
      dietary behaviors concurrently so that future interventions are more efficacious
      and efficient. Another lesson revealed the need for more sensitive measures, and
      examination of ways to improve intervention adherence and retention and prevent
      relapse.

PMID- 15989167
TI  - Ethnic differences in predictors of hearing protection behavior between Black and
      White workers.
AB  - The purpose of the study is to determine whether there are ethnic differences in
      predictors of hearing protection behavior between Black and White workers. The
      Predictors of Use of Hearing Protection Model (PUHPM) derived from Pender's
      Health Promotion Model (Pender, 1987) was used as a conceptual model. A total of
      2,119 (297 Blacks, 1,822 Whites) were included in the analysis. Internal
      consistency of instrument items was assessed using theta reliability estimates.
      Significant predictors of the use of hearing protective devices (HPDs) for Black
      and White workers and differences in predictors between the two groups were
      examined using multiple regression with interaction terms. Ethnic differences in
      scale or individual item scores were assessed using chi-square and t-test
      analyses. Different factors influenced hearing protection behavior among Black
      and White workers. The model was much less predictive of Blacks' hearing
      protection behavior than Whites' (R2 = .12 vs. .36). Since the PUHPM was not as
      effective in predicting hearing protection behavior for Blacks as for Whites,
      future studies are needed to expand the PUHPM through qualitative study and to
      develop culturally appropriate models to identify factors that better predict
      hearing protection behavior as a basis for developing effective interventions.

PMID- 15989168
TI  - Depression and suicidal ideation among Mexican American school-aged children.
AB  - The purpose of this study was to describe depression and suicidal ideation rates
      in a community sample of 182 urban fourth and fifth grade Mexican American
      children using the Children's Depression Inventory (CDI). We used a descriptive
      secondary data analysis design. The mean CDI score was 9.55 (SD = 5.8). Thirty
      one percent fell in the depressed range using a clinical cut point of 12 and 7%
      fell into the depressed range using the non-clinical cut point of 19. Thirty
      eight percent (n = 69) reported suicidal ideation. The depression rate was
      consistent with national rates. A non-clinical cut point of 19 showed that 87% of
      children reporting suicidal ideation were not identified as depressed. Many of
      these children do not report the most typical symptoms of depression. The results
      of this study provide school nurses with vital information to support efforts
      addressing the mental health needs of Mexican American children.

PMID- 15989169
TI  - The lived experience of moral distress: nurses who assisted with elective
      abortions.
AB  - The concept of moral distress has been studied mainly as an occupational issue
      and has not been developed for use in clinical practice. This study was designed
      to bridge prior studies of occupational moral distress with future clinical
      investigations of moral distress. Study aims were to discover the essence,
      properties, and full content domain of the concept of moral distress in order to
      develop a universal definition of the concept. A modified phenomenological study
      of nurses' experience of a particular moral issue was conducted. A maximum
      variation sampling strategy was used to recruit a final sample of registered
      nurses (N = 10). Interior aversion is the essential act of moral distress. Five
      properties of the lived experience of moral distress were identified: perception,
      pain, valuing, altered participation, and perspective. Three types of moral
      distress identified in this study were: shocked, muted, and suppressed
      (persistent). Type of moral distress was related to situational conditions,
      recognition of moral ends, quality of coping processes, and temporal breadth.
      Negative outcomes of moral distress, which probably exist, were undetectable with
      this study design. The definition has been composed in universal terms, but
      remains tentative, since the full content domain of moral distress was largely
      but not definitively identified.

PMID- 15989170
TI  - USDA takes steps to battle CWD.

PMID- 15989171
TI  - Coalition aims to generate veterinary pathologists.

PMID- 15989172
TI  - Peddie leaves lasting assets.

PMID- 15989173
TI  - Laugh yourself healthy: studies show humor-health link.

PMID- 15989174
TI  - Questions limitation in treatment of hepatozoonosis.

PMID- 15989175
TI  - Requests clarification on loan consolidation.

PMID- 15989176
TI  - Sees more to the large animal veterinarian shortage.

PMID- 15989177
TI  - Effects of animal rights issues on the veterinary profession.

PMID- 15989178
TI  - What is your diagnosis? Interstitial disease with alveolar infiltration.

PMID- 15989179
TI  - ECG of the month. Atrial flutter.

PMID- 15989180
TI  - Use of a eutectic mixture of lidocaine 2.5% and prilocaine 2.5% as a local
      anesthetic in animals.

PMID- 15989181
TI  - Extralabel intramammary use of drugs in dairy cattle.

PMID- 15989182
TI  - Characteristics of pain and response to analgesic treatment in dogs and cats
      examined at a veterinary teaching hospital emergency service.
AB  - OBJECTIVE: To estimate the prevalence and characteristics of pain in dogs and
      cats examined by an emergency service at a veterinary teaching hospital and
      evaluate the response of dogs and cats with signs of pain to analgesic treatment.
      DESIGN: Cross-sectional study. ANIMALS: 317 dogs and 112 cats. PROCEDURE: A
      questionnaire was used to categorize the characteristics of pain. The location,
      cause, and signs of pain were determined by obtaining a thorough history and
      conducting a physical examination. Pain was categorized by type (superficial
      somatic, deep somatic, or visceral), mechanism (inflammatory, neuropathic, or
      both), severity (mild, moderate, or severe), and duration. Evidence for primary
      or secondary hypersensitivity and hyposensitivity to manipulation was determined.
      The response to single or multiple analgesic drug administration was assessed.
      RESULTS: 179 (56%) dogs and 60 (54%) cats had signs of pain. In most of these
      dogs and cats, pain was classified as acute (< 24 hours' duration) and of
      moderate severity and was associated with primary hypersensitivity. Most dogs had
      deep somatic pain; most cats had visceral pain. Inflammation was the most common
      mechanism. One hundred nineteen (66%) dogs and 41 (68%) cats were treated with
      analgesic drugs. Analgesic treatment was considered effective in 73 (61%) dogs
      and 31 (76%) cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      moderate to severe acute somatic pain caused by inflammation is common in dogs
      and cats examined by an emergency service and that a combination of multiple
      analgesic drugs is more effective than any single analgesic drug in the treatment
      of pain in these dogs and cats.

PMID- 15989183
TI  - Use of pedometers to measure physical activity in dogs.
AB  - OBJECTIVE: To determine whether pedometers can be used to measure physical
      activity in dogs. DESIGN: Cross-sectional study. ANIMALS: 26 dogs. PROCEDURE: To
      determine pedometer accuracy, number of steps recorded with the pedometer as dogs
      walked, trotted, and ran for a distance of approximately 30 m (100 ft) at each
      gait was compared with actual number of steps. Dogs and owners then wore
      pedometers for 7 to 14 days, and dog pedometer output was compared with body
      condition score, owner-reported activity of the dog, and owner pedometer output.
      RESULTS: Most owners classified their dogs as active or quite active and
      indicated that their dogs exercised 3 to 7 days/wk. For all dogs, body condition
      score was 5, 6, or 7 on a scale from 1 to 9. At a walk, pedometers overestimated
      actual number of steps by approximately 17% in large and medium dogs and
      underestimated actual number of steps by approximately 7% in small dogs. No
      significant differences between pedometer-recorded and actual number of steps
      were detected when dogs trotted or ran. Number of steps per day for the dogs was
      significantly correlated with owner-reported activity of the dog (r = 0.305) and
      number of steps per day for the owners (r = 0.469) and was inversely correlated
      with body condition score (r = -0.554). CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that pedometers can measure physical activity in dogs with
      reasonable accuracy. A lower number of steps per day was associated with a higher
      body condition score, and less active owners generally had less active dogs.

PMID- 15989184
TI  - Isolation of necrotoxigenic Escherichia coli from a dog with hemorrhagic
      pneumonia.
AB  - A 7-month-old sexually intact male Cocker Spaniel was admitted to the North
      Carolina State University Veterinary Teaching Hospital for evaluation of
      lethargy, panting, and excessive salivation that had become progressively severe
      during a 5-hour period. Despite intensive medical care, the dog died within the
      first 24 hours of hospitalization, and death was attributed to acute, severe,
      necrotizing pneumonia. Lung tissue collected at necropsy by use of swabs was
      cultured and yielded an isolate of Escherichia coli; because of the rapid
      progression of illness in an otherwise healthy dog, the isolate underwent
      virulence typing and was determined to be a necrotoxigenic E. coli.
      Necrotoxigenic E. coli produce a toxin called cytotoxic necrotizing factor and
      are known to be involved in extraintestinal infections, including urinary tract
      infection, in humans and animals. Virulence typing of E. coli isolates from dogs
      with peracute pneumonia is recommended to further characterize the epidemiologic
      characteristics and public health importance of necrotoxigenic E. coli.

PMID- 15989185
TI  - Evaluation of ameroid ring constrictors for treatment for single extrahepatic
      portosystemic shunts in dogs: 168 cases (1995-2001).
AB  - OBJECTIVES: To evaluate use of an ameroid ring constrictor (ARC) for treatment
      for single extrahepatic portosystemic shunts (PSSs) and identify factors
      associated with postoperative death, continued portosystemic shunting, and long
      term outcome in dogs. DESIGN: Retrospective study. ANIMALS: 168 dogs with a
      single extrahepatic PSS. PROCEDURE: Medical records of dogs that had a single
      extrahepatic PSS and were treated with an ARC were reviewed. Signalment, history,
      clinical signs, results of preoperative blood analyses and portal pressure
      measurements, PSS location, ARC size, postoperative complications, and
      postoperative scintigraphy results were recorded. Owners were interviewed 6
      months to 6 years after surgery. Results-Postoperative complications developed in
      10% of dogs. Postoperative mortality rate was 7.1%. Predictive factors for
      postoperative death included high preoperative WBC count and postoperative
      complications. Twenty-one percent of dogs in which portal scintigraphy was
      performed 6 to 10 weeks after surgery had continued shunting. Predictive factors
      for persistent shunting included low preoperative plasma albumin concentration,
      high portal pressure after complete occlusion, and high portal pressure
      difference (postocclusion minus baseline). Clinical outcome in 108 dogs was
      classified as excellent (80%), good (14%), or poor (6%). Predictive factors for
      excellent long-term clinical outcome included high preoperative plasma albumin
      concentration, low preoperative leukocytosis, low portal pressure after complete
      occlusion, absence of postoperative seizures, and absence of continued shunting.
      CONCLUSIONS AND CLINICAL RELEVANCE: Use of an ARC for treatment for a single
      extrahepatic PSS resulted in low morbidity and mortality rates. Certain
      preoperative factors were associated with increased risk of postoperative death,
      continued portosystemic shunting, and long-term outcome.

PMID- 15989186
TI  - Evaluation of Lactobacillus pentosus WE7 for prevention of diarrhea in neonatal
      foals.
AB  - OBJECTIVE: To evaluate the efficacy of Lactobacillus pentosus WE7, an equine
      origin organism with potentially beneficial in vitro properties, as a probiotic
      for prevention of neonatal diarrhea in foals. DESIGN: Randomized controlled
      clinical trial. ANIMALS: 153 foals. PROCEDURE: Foals were enrolled at 24 to 48
      hours of age and randomly assigned to treatment or control groups. The treatment
      group received approximately 2 x 10(11) CFU of freeze-dried L. pentosus WE7
      orally once daily for 7 days, whereas the control group received a placebo.
      Clinical monitoring was performed for 14 days. RESULTS: Probiotic administration
      was significantly associated with development of signs of depression, anorexia,
      and colic and the need for veterinary examination and treatment. Probiotic
      treated foals also had more days of diarrhea, compared with the control group,
      although not significantly. In a multivariate model, probiotic administration was
      significantly associated with development of diarrhea and diarrhea plus
      additional clinical abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of L. pentosus WE7 did not prevent diarrhea; rather, it was
      associated with development of diarrhea and, most importantly, development of
      diarrhea plus additional clinical abnormalities and the need for veterinary
      intervention. The promising in vitro properties of L. pentosus WE7 were not
      evident in vivo. Results raise concern about the variety of untested probiotic
      products that are commercially available. Safety and efficacy testing needs to be
      performed for all potential equine probiotics.

PMID- 15989187
TI  - Septic arthritis and granulomatous synovitis caused by infection with
      Mycobacterium avium complex in a horse.
AB  - A 12-year-old American Saddlebred gelding was referred to a veterinary teaching
      hospital for evaluation of a chronic lameness problem in the right radiocarpal
      joint. The horse had been treated for osteoarthritis of the right radiocarpal
      joint with multiple injections of cortisone during the past 3 years. The horse
      was severely lame on the right forelimb at a trot. Radiography and computed
      tomography revealed a 3 x 2-cm lytic defect in the distal portion of the radius
      and periarticular bone proliferation around the right radiocarpal joint.
      Ultrasonography of the distal portion of the radius revealed a soft tissue mass
      in the palmarolateral aspect of the joint. Proliferative synovium with a large
      amount of fibrin was observed in the dorsal and palmar aspects of the joint via
      arthroscopic examination of the right radiocarpal joint. Histologic examination
      of synovial biopsy specimens revealed proliferative granulomatous synovitis with
      giant cells. Mycobacterium avium complex was cultured from the synovial fluid.
      Infection with M avium complex should be considered in horses with chronic
      recurring arthritis associated with granulomatous synovitis.

PMID- 15989188
TI  - Intravascular hemolysis associated with severe cutaneous burn injuries in five
      horses.
AB  - Five horses were evaluated because of severe cutaneous burn injuries following a
      barn fire. Gross hemolysis and morphologic changes in RBCs consistent with
      oxidative damage were detected in all of the horses. Of these horses, 4 became
      azotemic. The overall goals of treatment included wound care, correction of
      dehydration and provision of diuresis, control of inflammation, pain management,
      and prophylaxis against sepsis. After treatment, 2 horses survived and were
      discharged from the hospital. Red blood cell damage and hemolysis following
      cutaneous burn injury have been investigated in other species and appear to be a
      result of the release of oxygen radicals from complement-activated neutrophils.
      Early intervention with aggressive fluid therapy is recommended in the treatment
      of human burn patients and is likely to be of benefit in horses with burn
      injuries; a beneficial role of free radical scavengers and xanthine oxidase
      inhibitors has also been suggested.

PMID- 15989189
TI  - Effect of intrauterine administration of ceftiofur on fertility and risk of
      culling in postparturient cows with retained fetal membranes, twins, or both.
AB  - OBJECTIVE: To determine the effect of intrauterine administration of ceftiofur
      sodium on fertility and the risk of culling in postparturient cows with retained
      fetal membranes (RFM), twins, or both. DESIGN: Single-blind randomized clinical
      trial and prospective cohort study. ANIMALS: 2442 cows that calved from January
      1, 2000, to May 31, 2001. PROCEDURE: Cows with RFM, twins, or both were randomly
      allocated to control or treatment (ceftiofur) groups. Ceftiofur-group cows
      received 1 g of ceftiofur sodium sterile powder reconstituted with 20 mL of
      sterile water as a single intrauterine infusion once between 14 and 20 days after
      parturition. Control-group cows received no treatment. Cows that calved but did
      not have RFM or twins were considered the referent group. Reproductive, culling,
      and health data were recorded. RESULTS: There was no significant difference in
      the overall proportion of ceftiofur-group cows confirmed pregnant, compared with
      cows in the control group. Ceftiofur-group cows were significantly less likely to
      be culled and were culled at a later time in lactation than control-group cows.
      In the cohort study, the risk of pregnancy and the risk of being culled in
      ceftiofur-group cows were not significantly different from cows in the referent
      group. CONCLUSIONS AND CLINICAL RELEVANCE: Intrauterine treatment of cows with
      RFM, twins, or both with ceftiofur sodium increased longevity of cows in the herd
      as measured by the risk of culling and the time to culling. Intrauterine
      administration of ceftiofur in cattle is considered extralabel drug use, and the
      attending veterinarian must follow the AMDUCA guidelines for extralabel drug use.

PMID- 15989190
TI  - Evaluation of the efficacy of disinfectant footbaths as used in veterinary
      hospitals.
AB  - OBJECTIVE: To evaluate efficacy of 2 disinfectants as used in footbaths in
      veterinary hospitals for reducing bacterial contamination of footwear. DESIGN:
      Prospective study. SAMPLE POPULATION: Bacteria collected from the soles of rubber
      boots after experimental contamination and exposure to disinfectant solutions or
      control conditions. PROCEDURES: Investigators contaminated boots by walking
      through soiled straw animal bedding. Swab samples were collected from the sole of
      1 boot (right or left) without treatment. The other boot was briefly immersed in
      a disinfectant solution (either a quaternary ammonium compound [QAC] or a
      peroxygen compound) or water, and samples were collected after 7 minutes.
      Differences associated with the experimental treatments were analyzed
      statistically. Veterinary teaching hospitals (VTHs) in the United States and
      Canada were contacted to obtain information about the use of footbaths. RESULTS:
      Mean bacterial concentrations from peroxygen-treated boots were 67% to 78% lower,
      compared with samples taken from untreated boots. In contrast, there were no
      statistically detectable differences in mean bacterial concentrations in samples
      taken from QAC- or water-treated boots, compared with control boots. Disinfectant
      footbaths were reportedly used in 30 of 31 VTHs. CONCLUSIONS AND CLINICAL
      RELEVANCE: Disinfectant solution containing peroxygen applied in a footbath
      reduced bacterial concentrations on rubber boots under conditions representative
      of those found in VTHs. Footbaths are commonly used as a method to control
      infectious diseases in veterinary hospitals. Disinfectant footbaths should not be
      expected to sterilize footwear, but they may help in reducing the risk for
      nosocomial infection when used with effective disinfectants.

PMID- 15989191
TI  - Eastern equine encephalitis in a flock of African penguins maintained at an
      aquarium.
AB  - Eastern equine encephalitis (EEE) was diagnosed in a flock of African penguins.
      Diagnosis was based on history and clinical signs and confirmed via serologic
      testing, virus isolation, reverse transcriptase-polymerase chain reaction (RT
      PCR) assay, and histologic examination. Clinical signs in penguins included
      anorexia, behavior changes, depression, regurgitation, ataxia, recumbency, and
      seizures, and some penguins did not have any clinical signs. Mean +/- SD number
      of days that affected penguins had clinical signs was 12 +/- 5 days.
      Abnormalities initially detected on CBC included heterophilic leukocytosis and
      anemia; lymphocytosis and monocytosis were detected later. Plasma biochemical
      abnormalities included high activities of aspartate amino-transferase and
      creatine kinase, hyponatremia, hypochloremia, hyperglycemia, and high
      concentrations of globulin, triglycerides, and cholesterol. Mean +/- SD number of
      days required for resolution of CBC and plasma biochemical abnormalities was 67
      +/- 24 days after the onset of clinical signs. Treatment consisted of supportive
      therapy. All penguins survived with the exception of one that was euthanatized;
      histopathologic findings were consistent with encephalitis. Results of RT-PCR
      assays performed on tissue from the right cerebrum of the penguin that was
      euthanatized were positive for EEE viral RNA. An inability to isolate virus
      several weeks after illness suggested successful viral clearance in recovered
      penguins. To the authors' knowledge, EEE infection in any penguin species has not
      been reported.

PMID- 15989195
TI  - The mystery of healing.

PMID- 15989196
TI  - Why in the world is there suffering?

PMID- 15989197
TI  - Florence Nightingale's changing image? Part I: Nightingale the feminist,
      statistician and nurse.

PMID- 15989198
TI  - Can music help us heal?

PMID- 15989199
TI  - The patchwork quilt: healing after sexual abuse.

PMID- 15989200
TI  - A gift from God: healing from ovarian cancer.

PMID- 15989201
TI  - No end in sight: living with chronic pain.

PMID- 15989202
TI  - A grim prognosis: can hope survive?

PMID- 15989203
TI  - Nursing diagnosis: chronic sorrow.

PMID- 15989204
TI  - Close calls in Iraq.

PMID- 15989206
TI  - Newer challenges for influenza prevention. Lessons from 2004-2005.

PMID- 15989208
TI  - Pain and discomfort associated with mammography among urban low-income African
      American women.
AB  - African-American women have lower rates of breast cancer screening than Caucasian
      women. Discomfort during mammography may deter women from rescreening. Research
      to date has focused primarily on Caucasian women. This study examined mammography
      associated discomfort among urban, low-income African-American women, and how
      discomfort influenced rescreening intentions. Using survey data from 530 urban
      African-American women aged 45 years and older, we assessed sociodemographic,
      psychological, and health-related predictors of pain or discomfort, and
      associations between pain or discomfort and intention for rescreening. Seventy
      six percent of women reported discomfort; reasons included machine compression
      (96%), breast size (36%), stature (30%), and roughness by technicians (18%).
      Intention to rescreen within 2 years was significantly reduced with reporting any
      discomfort (OR 0.61; 95% CI: 0.38, 0.98), reporting two specific reasons-stature
      (OR 0.47; 95% CI: 0.31, 0.72) and technician roughness (OR 0.43; 95% CI: 0.26,
      0.72), and attributing more sources for pain or discomfort (p for trend = 0.02).
      Most women reported discomfort; for some, this influenced intended adherence.
      Offering women the opportunity to control the amount of compression may reduce
      the pain associated with mammography and subsequently increase compliance.

PMID- 15989207
TI  - Measuring sustained mammography use by urban African-American women.
AB  - Although the numbers of African-American women who are 'ever' screened for breast
      cancer has increased, sustaining regular screening over a lifetime remains a
      problem. Face-to-face interviews about breast cancer screening were conducted
      with 576 African-American women from an east coast city. The well-screened index
      measuring adherence to breast cancer screening guidelines was developed and
      tested. This index incorporated a woman's past and present use of mammography
      plus her future intent to be screened. Respondents were dichotomized into well
      screened and not well-screened groups. Social and psychological factors
      associated with sustained screening as measured by this index were then explored.
      In bivariate analyses, education, health insurance, usual source of care,
      chronicity and preference for provider ethnicity and gender were significantly
      different for the two groups. In the multivariate model, women who were well
      screened were significantly more likely to report recent physician contact, Pap
      smear, dental visit, history of breast problems, and beliefs that screening
      should be done annually and that early detection improves outcomes. Women
      reporting poor health were less likely to be well-screened. The well-screened
      index can potentially be used for assessment by clinicians and for program
      evaluation; however further validation studies need to be conducted. Despite
      limited resources, the majority of these urban African-American women are
      building lifetime patterns of regular breast cancer screening. Focused efforts
      are needed to achieve sustained screening patterns in the 25% who are not
      regularly screened.

PMID- 15989209
TI  - The association of distraction and caution displayed by pedestrians at a lighted
      crosswalk.
AB  - The rates of deaths and injuries among pedestrians have fallen in recent years,
      but still remain public health problems as about 5000 pedestrians die each year.
      Because pedestrians have been shown to be responsible or partially responsible
      for many of the crashes in which they are involved, we sought to assess the
      relationship of distracted walking and performing routine cautionary behaviors of
      pedestrians crossing a busy street in a southwestern city at an intersection,
      adjacent a university. The behavior of 866 individuals was recorded by trained
      observers as pedestrians walked across a 105-foot wide street served by a stop
      light and zebra painted crosswalk. We defined distracted pedestrians as those
      wearing headphones, talking on a cell phone, eating, drinking, smoking or talking
      as they crossed the street. Caution was measured by looking left and right, and
      entering the crosswalk only when the white proceed light was illuminated. We
      found that only 13.5% of walkers looked left and right and entered the crosswalk
      while the white light was flashing. Approximately 20% of walkers were distracted
      as they crossed the street. Regression analysis indicated that distraction was
      negatively, but weakly associated with displaying cautious pedestrian behaviors.
      Because traffic lights were routinely ignored and lack of caution was predicted
      by distraction, we suggest that inexpensive education efforts target pedestrians
      near college campuses.

PMID- 15989211
TI  - Use of a patient assistant to facilitate medical visits for Latino patients with
      low health literacy.
AB  - In the face of limited resources, evidence-based prioritization is needed to
      maximize the reach of health services for the underserved. A medical referral
      project that referred low income uninsured individuals to discounted appointments
      with office-based doctors found that some Latino patients had difficulty in
      taking advantage of these appointments. These individuals appeared to face
      barriers beyond the cultural and linguistic barriers faced by most patients in
      the project. One additional bilingual staff person, a Patient Assistant, was
      hired to facilitate doctor visits by these patients. The Patient Assistant
      performed the duties of a navigator, trouble shooter, and interpreter--and
      assisted with communications. The project staff derived a screening question to
      encourage patients to identify themselves as those who would need the help of the
      Patient Assistant. These patients were subsequently questioned in a waiting room
      survey designed to characterize them. The characteristics of these patients were
      compared with a comparison group of project patients. The target group and the
      comparison group differed in their levels of education. Sixty percent of the
      target group had less than 4 years of schooling compared to 13% of the comparison
      group. The target group was comprised entirely of immigrants from South and
      Central America. This report underscores the conclusions of the recent report of
      the Institute of Medicine on the problem of health literacy--patients' ability to
      understand and act in their own interest--and highlights the needs of Latin
      American immigrants who are burdened by cultural and linguistic barriers, low
      health literacy, and minimal education.

PMID- 15989210
TI  - Osteoporosis medications used by older African-American women: effects of
      socioeconomic status and psychosocial factors.
AB  - This study examined the effects of socioeconomic status, knowledge and Health
      Belief Model variables on ever use of hormone therapy and other osteoporosis
      medications among older African-American women. One-hundred and two African
      American women, 60 years old or older, randomly selected from Registers of Voters
      and a list of participants in educational activities of a university hospital,
      were interviewed in their homes. Data collected concerned knowledge of
      osteoporosis, Health Belief Model variables, and cues to action such as history
      of hysterectomy, personal and family history of cancer, bone mineral density
      testing, and discussion with a physician about osteoporosis. Socioeconomic status
      indicators included years of education and household income. The average
      respondent age was 71.1 years; 47% were current or previous users (ever users) of
      hormone therapy, and 11% were ever users of other osteoporosis medications.
      Knowledge of osteoporosis, (odds ratio = 1.4), Hormone therapy benefits, (odds
      ratio = 1.63), a hysterectomy (odds ratio = 4.35), and a family history of cancer
      (odds ratio = 4.0) increased the odds of ever using hormone therapy. Perceptions
      of susceptibility (odds ratio = 3.5) and discussion with a physician about
      osteoporosis (odds ratio = 6.4) increased odds of ever using other osteoporosis
      medications. Socioeconomic status mediated the effects of knowledge of
      osteoporosis on ever using hormone therapy. Efforts to promote bone health to
      older African-American women should focus primary efforts to increasing
      perceptions of susceptibility to fracture and persuading physicians to initiate
      discussions about fracture prevention with African-American patients before a
      fracture occurs.

PMID- 15989212
TI  - A. Lincoln, esquire defends the murderer of a physician.
AB  - After only about a year of law practice, Abraham Lincoln participated in his
      first murder trial. Dr. Jacob M. Early was shot and killed in a bitter political
      imbroglio. Lincoln joined a defense team of highly accomplished litigators.
      Despite his having the least legal experience, he was selected to give the
      defense summation. In his argument, he spoke to the jury in a conversational tone
      making his point that Dr. Early had a deadly weapon in his hands, namely an
      upraised wooden chair, when he was shot. His self-defense plea indicated that
      Henry B. Truett, the defendant, truly believed that he was in danger of being
      crushed by the upraised chair. Interestingly, Lincoln knew both the defendant and
      the murdered physician. He handled litigation for the former and served in the
      Black Hawk War under the command of the latter. Furthermore Lincoln knew at least
      five of the jurors.

PMID- 15989213
TI  - Stewardship and accountability.
AB  - In March 2003 The Chronicle for Philanthropy reported a sea change in fund
      development. After 25 years of consistent research on donor motivation, a study
      came out with new information. Donors ranked on a scale of 1-10 what mattered
      most to them when considering giving. Until now, most donors reported that a
      belief in the mission of the organization and the desire to have an impact on the
      people served was their number one motivation. Certainly gratitude for life
      saving or life-changing service made that belief in mission and impact that much
      more powerful as a motivation. Improving their community was consistently the
      number two reason for giving. But, according to the 2003 survey, something
      changed. Six of the 10 reasons involve stewardship and accountability.

PMID- 15989214
TI  - Building relationships a giver at a time.
AB  - In his book, Servanthood: Leadership for the Third Millennium, Bennett Sims
      states boldly, "To challenge people to give is to do them a favor." As
      development professionals, do we truly agree? When we ask someone to give, do we
      believe we are doing them a favor? To challenge people to give, our greatest
      effort should center on creating meaningful donor relationships.

PMID- 15989215
TI  - Moves Management for physician fundraising in a capital campaign.
AB  - Hospitals are turning to philanthropy as a significant source of funding for
      capital programs, and physicians are a key resource. Through their own giving and
      their community-wide influence, physicians provide a high return on capital
      campaign investment. By adapting Moves Management, the premier method for
      prospecting and cultivation, development officers can achieve a high rate of
      participation by the hospital's physicians and, through them, attain increased
      community giving. Moves Management is defined as a process that involves managing
      a series of steps (moves) with identified prospects (the 10 percent who can give
      90 percent). The number and type of steps depend upon the individual involved,
      such that each prospect is moved from attention to interest to desire to action
      and then back to interest until he or she has given everything he/she will or can
      to the organization.

PMID- 15989216
TI  - Hospital quality is directly related to success in philanthropy.

PMID- 15989217
TI  - Taking the high road.
AB  - Somehow, over time, ethics has been neglected at conferences and even in articles
      in many association publications. Thinking about how many times we open the
      newspaper to read about corporate scandals, why shouldn't we be just as concerned
      about the "ethics" of how we go about our business of fundraising?

PMID- 15989218
TI  - [Identification of ammonia oxidation Streptomyces strain A2 and study of its
      autotrophic ammonium oxidation characteristics].
AB  - Streptomyces strain A2 was isolated from a nitrification reactor. According to
      the characteristics of morphology, cultivation, physiology, (G + C)mol% content,
      16S rDNA sequence and DNA-DNA hybridization. it was identified as Streptomyces
      bikiniensis. Strain A2 could heterotrophically grow on YD medium and could also
      autotrophically grow on inorganic medium. The heterotrophical growth rate
      (0.39mg/L.d) was higher than the autotrophical growth rate (0.22mg/L.d). During
      heterotrophical growth ammonia was mainly assimilated. During autotrophical
      growth, however, one part of ammonia was assimilated and other part of ammonia
      was converted into nitrite. When grown on the inorganic medium, the maximum
      ammonium oxidation rate reached at ammonium concentration of 118mgN/L. The
      optimal pH for growth and ammonia oxidation was 9.36 and 9.29, respectively. The
      optimal temperature for growth and ammonia oxidation was 31 degrees C and 40.6
      degrees C, respectively. A high concentration of dissolved oxygen was good for
      growth and ammonia oxidation, and growth was more sensitive to dissolved oxygen
      change than to ammonia oxidation.

PMID- 15989219
TI  - [Isolation and identification of a Streptomyces strain against ginger bacterial
      wilt caused by Pseudomonas solanacearum Smith].
AB  - Streptomyces SR-11 was isolated from the soil of ginger in Sichuan Province
      against ginger bacterial wilt caused by Pseudomonas solanacearum Smith. It had
      distinctively inhibitive effect on gram-positive bacterium, gram-negative
      bacterium and some kinds of pathogenic fungi. It's morphological, cultural
      physiological, biochemical characteristics, chemotaxonomy and 16S rDNA sequences
      analysis were studied. The substrate mycelium have no partition, the aerial
      mycelium are ramose; The spore-bearing filaments are spiral, the spores are oval
      and the surface are smooth. Cell wall type I, Sugar type C. When SR-11 is
      matured, the aerial mycelium are gray and the strain can give out an earthy
      smell. A phylogenetic tree was constructed by comparing with the published 16S
      rDNA sequences of the related bacteria species. In the phylogenetic tree the
      overall similarity value between strain SR-11 and 12 type Streptomyces sp are
      96.5-98.3%.

PMID- 15989220
TI  - [Molecular analysis of the microbial communities of the Dagang Kongdian flooding
      bed oilfield].
AB  - Both PCR-TGGE (temperature gradient gel electrophoresis, TGGE) and 16S rRNA gene
      clone library construction were used to comparatively analyze the microbial
      communities of a water injection well (WW) and an oil well (OW) in Dagang
      oilfield. TGGE analysis of the PCR amplified 16S rDNA V3 region products showed
      great difference between these two microbial communities. Six major bands were
      detected in the TGGE profile of the WW sample, while only one predominant band in
      the OW sample was found. Two 16S rRNA gene clone libraries were also constructed,
      and 108 and 50 clones were selected from the WW and OW library respectively for
      amplified ribosomal DNA restriction analysis (ARDRA). 33 taxanomic operational
      units (OTUs) were found in the WW library with 6 major OTUs, while only 8 OTUs
      were found in the OW library with one OTU predominant. The results of TGGE and
      clone library profiling analysis both indicated that microbial community of the
      WW had higher diversity than the OW. Sequence analysis of the representative
      clone of each OTU showed that most bacteria of the WW were affiliated with alpha,
      beta, and gamma Proteobacteria and Actinobacteria, especially Rhodobacter (47%).
      Most bacteria of the OW were affiliated with alpha, beta, and gamma
      Proteobacteria, especially Pseudomonas (62%). Molecular analysis of the microbial
      diversity in oilfield provides foundation for better application of MEOR
      (Microbial Enhanced Oil Recovery).

PMID- 15989221
TI  - [Molecule biology study on the effective bacteria in ANAMMOX sludge].
AB  - A greater understanding of anaerobic ammonium oxidation bacteria will help to
      pave the way for the new biological nitrogen removal process application in
      practice. To this end, this study used molecule biology methods. Crude DNA of the
      total bacteria in a cultivated sludge with ANAMMOX capability was extracted and
      purified. Then PCR amplification using specific primers, clone and sequencing
      processes were performed. The partial 16S rDNA sequence of cultivated ANAMMOX
      bacteria is 836bp. Some clones have one to two base mutation(s). Phylogenetic
      analysis indicates that the cultivated ANAMMOX bacteria in this study close to
      Candidatus Brocadia anammoxidans, anaerobic ammonium-oxidizing Planctomycete and
      uncultured anoxic sludge bacterium KUI with the same function, whereas the
      cultivated ANAMMOX bacteria are relatively low DNA sequence similarity to the
      forementioned bacteria using alignment analysis. The results suggest that there
      is a kind of bacterium which has never been found before with ANAMMOX capability
      existing in nature.

PMID- 15989222
TI  - [Transcriptional regulation of noeAB from Sinorhizobium meliloti 042BM].
AB  - The expression regulation of S. meliloti 042BM noeAB was studied. The results
      showed that trigonelline could not elevate the level of noeAB expression, which
      indicated that these genes are not regulated by nodD2. Since association of nodD3
      and syrM could not change the level of the genes expression, they aren't also
      controlled by nodD3-syrM system. However, induction of luteolin resulted in 16
      times increase of noeAB expression, which indicated that noeAB was regulated by
      nodD1. Most interestingly, more than 30 times increase in its expression was
      observed on TY medium without any flavonoid. Thus, it was suggested that noeAB
      may be controlled by other unknown factors.

PMID- 15989223
TI  - [Transcriptional repression of pltZ on pyoluteorin ABC transporter of Pseudomonas
      sp. M18].
AB  - A pltZ gene involved in negatively regulating pyoluteorin (Plt) biosynthesis, and
      an ABC (ATP-binding cassette) transporter involved in pyoluteorin secretion and
      itself resistance, were identified downstream of Plt biosynthesis gene cluster in
      Pseudomonas sp. M18. The ABC transporter gene pltH'-lacZ translational and
      transcriptional fusion expression plasmids, pHZLF and pHZCF, were constructed
      using promoter probe vector pME6015 and pME6522 respectively, and then were
      introduced into the wild-type strain of Pseudomonas sp. M18 and the pltZ mutant
      strain M18Z. The chromosomal pltZ disruption mutant gave rise to 3.7-8.4-fold
      enhancement of translational pltH'-'lacZ fusion expression and 2.8-7.4-fold
      enhancement of transcriptional pltH'-'lacZ fusion expression compared with those
      in the wild-type strain M18. These results suggested that pltZ can repress
      transcription of Plt ABC transporter, and it can indirectly regulate Plt
      biosynthesis negatively through the Plt ABC transporter system.

PMID- 15989224
TI  - [Construction and characterization of Salmonella typhimurium SL7207 SifA- mutant
      strain].
AB  - One characteristic of Salmonella typhimurium SifA- mutant strain is to enter the
      cytosol of eukaryotic cells. The SifA- mutation of S. typhimurium P3H6 was
      transferred into S. typhimurium vaccine vector SL7207 by P22 phage transduction
      and the new strain was named as SL7207*. SL7207* had similar growth curve in LB
      medium and similar invasiveness for eukaryotic cells. It was found that SL7207*
      replicates within MDCK cells at a higher rate than SL7207, but is defective for
      replication in macrophage cell line RAW264.7. SL7207* was more attenuated than
      SL7207 in BALB/c mice when innoculated intraperitoneally or intravenously.
      SL7207*, but not SL7207, could transfer eukaryotic expression plasmid into
      RAW264.7 cells. These results showed that SL7207* could be a promising candidate
      vaccine vector to express foreign antigen or act as a eukaryotic expression
      plasmid carrier.

PMID- 15989225
TI  - [Breeding of high-yield strain of taxol by mutagensis of protoplast and primary
      discussion of genetic differences between mutants and their parent strain].
AB  - The breeding of high-yield strain of taxol was performed by protoplast
      mutagenesis of strain NCEU-1 using ultraviolet radiation and combined treatment
      of UV and LiCl. The mutants UV40-19 and UL50-6 were obtained, which raised the
      taxol yield from 314.07 microg/L to 376.38 microg/L and 392.63 microg/L
      respectively. Genetic differences between the mutants UV40-19, UL50-6 and their
      parent strain were primarily compared through random amplified polymorphic DNA
      (RAPD) and isozyme technique. The results showed that the genetic differences
      were very obviously between the parent strain and its mutants and between the two
      mutants, which laid foundation of molecular mechanism for the study of genes
      related to the taxol biosynthesis and mutants for raising the taxol yield.

PMID- 15989226
TI  - [Influence of nonessential region on protective efficacy of recombinant fowlpox
      viruses].
AB  - Because of the interference of maternal antibodies, the recombinant fowlpox virus
      (rFPV) vaccine has not been used widely. The selection of a well-defined FPV
      nonessential region might be a desirable way to solve this problem. Two pairs of
      primers were designed according to the genome of a pathogenic FPV to amplify two
      flanking regions (FPV1 and FPV2) of the supposed nonessential region by PCR, and
      then a series of plasmid vectors were constructed to generate the expression
      vector pP12LS, which containing FPV1, FPV2, the expression cassette of P11-LacZ
      reporter gene and the promoter Ps. To abtain the vector pP12LSF, the F gene of
      ZJ1 strain Newcastle Disease Virus (NDV) was inserted into pP12LS, in which the F
      gene was located downstream of the promoter Ps. pP12LSF was transfected into
      chicken embryo fibroblast (CEF) pre-nfected with 282E4 strain FPV. The
      recombinant FPV, rFPV-FSC, was purified by blue plaque selection. The LacZ and F
      genes could be expressed by rFPV-FSC after 20 successive passages in CEF. The FPV
      nonessential region was the only difference between rFPV-FSC and rFPV-FSB. These
      two rFPVs could induce completely protection in SPF chickens against lethal
      challenge with F48E8 strain NDV. However, the protective efficacy showed a
      significant difference in commercial chickens with maternal antibodies. The
      protective efficacy of rFPV-FSC was 100% and rFPV-FSB was 61.54%. The results
      indicate that the selection of a well-defined FPV nonessencial region is an
      effective way to increase the protective efficacy of rFPVs, especially in
      chickens with maternal antibodies.

PMID- 15989227
TI  - [Study on the characterization of the bi-directional promoter between pp38 gene
      and 1.8kb mRNA transcripts of Marek's disease viruses].
AB  - The bi-directional promoter between pp38 gene and 1.8kb mRNA transcripts of
      Marek's disease viruses (MDV) was divided into two single-direction promoters
      from the replication of MDV genomic DNA. The pp38 gene was cloned into pUC18
      vector for plasmid pUC-pp38. Then the complete bi-directional promoter was cloned
      into pUC-pp38 in two directions to form plasmids pPro(f)pp38 and pPro(r)pp38, and
      the divided two single directional promoters were cloned in pUC-pp38 for plasmids
      pdPro(f)pp38 and pdPro(r)pp38. 24 to 48 hours after transfection to chicken
      embryo fibroblast (CEF) cells, the expression of pp38 could be detected in above
      4 samples with Indirect Immuno-fluorescent Assay (IFA). In order to analysis the
      activity of the promoter quantificationally, CAT was used as the report gene. The
      complete or divided promoters were cloned into pCAT-Basic vector for plasmids
      pPro(f)CAT, pPro(r)CAT, pdPro(f)CAT and pdPro(r)CAT. The activity of CAT was
      measured from the lysed CEF cells, when they were transfected for 48 hours by the
      above four plasmids, respectively. The results showed the activity of the divided
      promoters reduce on both directions, especially for the direction of 1.8kb mRNA
      transcript, nearly down to 1/41.

PMID- 15989228
TI  - [Cloning and functional characterization of the gacS gene of the biocontrol
      strain Pseudomonas fluorescens 2P24].
AB  - Pseudomonas fluorescens 2P24, a biocontrol agent for soil-borne diseases has been
      isolated from the wheat take-all decline soil, and was characterized with
      efficient production of antifungal compounds. In this study, the gacS gene was
      cloned by PCR from the P. fluorescens 2P24 genomic library. Nucleotide sequencing
      indicated that the gacS gene contains 2754 bp, and is predicted to encode a
      peptide of 917 amino acids with molecular mass of 101 kD. The deduced amino acid
      sequence shares 91% identity to that of the sensor kinase GacS of P. chlororaphis
      and 89% identity to GacS of P. fluorescens CHAO. Further research revealed that
      the gacS-knock-out mutant was unable to produce anti-fungal metabolites, such as
      2,4-DAPG, HCN and proteinase. Moreover, it lost the ability to inhibit the growth
      of Gaeumannomyces graminis in Petri dish and to control the development of wheat
      take-all disease in greenhouse. The complemented strain containing a plasmid
      bearing gacS gene could restore all of the lost phenotypes. The results indicated
      that GacS in an important regulatory factor and directly controls the synthesis
      of key biocontrol factors and the biocontrol efficacy of P. fluorescens 2P24.

PMID- 15989229
TI  - [Generation of A/Chicken/Shanghai/F/98 (H9N2) avian influenza virus from eight
      plasmids].
AB  - Eight-plasmid system was used for the generation of Avian influenza virus (AIV)
      strain A/Chicken/Shanghai/F/98 (H9N2) which was isolated in China in 1998. In
      this plasmid-based expression system, viral cDNA was inserted beteen the RNA
      polymerase I (pol I) promoter and terminator sequences. The entire pol I
      transcription unit was flanked by an RNA polymerase II (pol II) promoter and a
      poly (A) site. Twenty-four hours after the transfection of eight expression
      plasmid into cos1 cells, the supernatant and cos1 cells transfected were
      inoculated into the allantoic cavity of 10-day-old specific-pothgen-free (SPF)
      chicken eggs. The HA titer was determined after passage of the rescued virus in
      chicken eggs, and as high as that of the parental wild-type virus.

PMID- 15989230
TI  - [Antigenic analysis of the recombinant capsid protein of porcine circovirus type
      2].
AB  - The nuclear localization signal (NLS)-defected capsid protein gene (dCap) of
      porcine circovirus type 2 (PCV2) was expressed firstly in Escherichia coli as a
      fusion protein with glutathione S-transferase (rGST-dCap protein). The purified
      rGST-dCap protein and NLS-defected Cap protein of PCV2 (rdCap protein) from the
      purified rGST-dCap protein reacted specifically with swine antiserum to PCV2.
      Furthermore, the obtained monoclonal antibodies (mAbs) to rdCap protein were
      shown to bind to PCV2 particles replicated in PK15 cell. MAbs to rdCap protein
      also revealed the neutralizing ability to PCV2 particles. These results
      demonstrate that rGST-dCap protein expressed in E. coli is folded correctly or at
      least partly, and all mAbs to rdCap protein possess the binding epitopes of PCV2
      particle whereas mAbs 4C4,3F6 and 2G7 to rdCap protein keep the neutralization
      epitopes of PCV2 particle, showing a potential of rGST-dCap protein as a vaccine
      antigen or serodiagnostic reagent.

PMID- 15989231
TI  - [Construction of recombinant Escherichia coli strains producing poly (4
      hydroxybutyric acid) homopolyester from glucose].
AB  - The aim of this study is to construct recombinant Escherichia coli strains
      capable of producing poly(4-hydroxybutyric acid) homopolyester from glucose as
      sole carbon source. A glutamate: succinate semialdehyde transaminase gene from
      Escherichia coli, a glutamate decarboxylase gene from E. coli, and a 4
      hydroxybutyrate dehydrogenase gene from Ralstonia eutropha were cloned by PCR and
      assembled onto the plasmid pKSSE5.3 which haboured the PHA synthase gene from
      Ralstonia eutropha and 4-hydroxybutyrate: CoA transferase from Clostridium
      kluyveri. The resulting plasmids were transformed into E. coli and the pathway
      for biosynthesis of poly(4-hydroxybutyric acid) from glucose via alpha
      ketoglutarate, an intermediate in TCA cycle was established in recombinant E.
      coli strains. Recombinant strains synthesized the homopolyester P(4HB), when
      cells were cultivated in Luria-Bertani broth with glucose as carbon source.
      P(4HB) accumulation was enhanced up to 30% of cell dry weight, when cells were
      cultivated in mineral salts M9 medium plus glucose as sole carbon source with
      addition of yeast extract, tryptone, casein hydrolate into medium respectively.

PMID- 15989232
TI  - [Expression of porcine interleukin-6 in Pichia pastoris].
AB  - As a kind of pleiotropic cytokine, Interleukin-6 (IL-6) becomes more and more
      popular in the fields of disease diagnosis and candidate adjuvants. In this
      study, the porcine Interleukin-6 (pIL-6) cDNAs un-coding signal peptides was
      cloned into pPIC9K (the expression vector of Pichia pastoris) to construct the
      pPIC9K-IL6, which was further transformed into P. pastoris GS115 strain. After
      being induced by 1% methanol, the recombinant strain excreted a protein in
      supernate of culture, with molecular weight of 24.5KD approximately, which was
      proved to be pIL6 through SDS-PAGE and western blotting. This P. pastoris product
      wasn't modified by N-hyperglycosylation. After purified, pIL-6 could reach to 8 x
      10(4) IU/mg of bioactivity unit by the cell proliferation of B9 assay. Through
      researching the characters of the recombinant protein pIL6, we have made a great
      progress on the study of rpIL6 as veterinary vaccine's adjuvant.

PMID- 15989233
TI  - [Construction of superagonist mutein of human CNTF and its expression in Pichia
      pastoris].
AB  - Human ciliary neurotrophic factor (hCNTF) and its derivatives are promising
      therapeutics for obesity associated with diabetes. To reduce its side effects and
      increase its efficacy, superagonist mutein of human CNTF was constructed by the
      introduction of S165D/Q166H mutation into AX15(R13K), which is a mutein of
      naturally occurring hCNTF, with improved biological activity, stability,
      solubility and KEX2 resistance. In vitro TF-1 cell survival assay and in vivo
      antiobesity tests showed DH-AX(R13K) was about 5 fold more potent than
      AX15(R13K). It was further demonstrated that the antiobesity effect of DH
      AX15(R13K) was more durable than that of AX15(R13K). The more durable effects of
      DH-AX15(R13K) is ascribed to its higher specific activity, but not to its
      prolonged half-life. The superagonist mutein of human CNTF would have an improved
      side effect profile and thus have superior therapeutic potential.

PMID- 15989234
TI  - [PCR detection of PCV-2 and PRRSV in porcine pleuropneumonia samples].
AB  - PCV-2 (Porcine circovirus type-2, PCV-2) and PRRSV (Porcine reproductive and
      respiratory syndrome virus, PRRSV) were detected by PCR from 253 porcine
      pleuropneumonia samples and 125 clinically healthy lung samples were collected
      from different districts of Shandong province. The results showed that 171
      samples for PCV-2 and 101 samples for PRRSV were positive. The positive ratio
      were 67.5% and 40%, respectively. The co-infection number of PCV-2 and PRRSV was
      68 in 253 samples, the positive ratio was 26.8%. While in the clinically healthy
      samples, only 21 samples for PCV-2 and 12 samples for PRRSV were detected
      positive, the positive ratio were 16.8% and 9.6%, respectively, no co-infection
      samples were found. Statistical result showed significant difference between
      positive ratio for PCV-2 and PRRSV in porcine pleuropneumonia samples and that of
      in clinically healthy samples. The above results demonstrated that there maybe
      some relationship between the infection of porcine pleuropneumonia and PCV-2 and
      PRRSV in pigs.

PMID- 15989235
TI  - [Study on rotavirus detection with single-tube seminested RT-PCR method in
      shellfish].
AB  - Being a foodborne virus, Rotavirus was often carried by shellfish. At the
      present, RT-PCR was the most effective method of Rotavirus detection in
      shellfish, but its sensitivity was low because of low levels of virus
      contamination and PCR inhibitors in shellfish. So contaminated shellfish
      experimentally in laboratory, and imitated the natural environment to concentrate
      Rotavirus, then detected by the developed single-tube seminested RT-PCR. Compared
      with ELISA and the conventional RT-PCR, the detection sensitivity is improved by
      1000 times and 10 times respectively. In addition, the outer and inner
      contamination is reduced dramatically and the detection time is decreased from 6h
      to 4.5h. When the whole shellfish and only the digestive tissues of shellfish
      serve as samples, the detection ratio and sensitivity are more higher when sample
      is the latter.

PMID- 15989236
TI  - [Regulatory effects of ammonium ions on the biosynthesis of meilingmycin].
AB  - Based on the effects of different ammonium sulfate concentrations on meilingmycin
      biosynthesis, the results show that lower concentration of ammonium ions
      stimulates the biosynthesis of meilingmycin, while the concentration of higher
      than 5mmol/L inhibits the mycelial growth and the biosynthesis of the products.
      However, the sugar consumption rate increases with the elevating concentration of
      ammonium sulfate. On this basis, six enzymes, which are greatly related to the
      meilingmycin biosynthesis and the glucose metabolism, were measured and analyzed
      during the meilingmycin fermentation process. The results suggest that glucose-6
      phosphate dehydrogenase, citrate synthase, succinate dehydrogenase and fatty acid
      synthase are stimulated by higher concentration of ammonium ions, while valine
      dehydrogenase and methylmalonyl-CoA carboxyltransferase are inhibited. From the
      results it follows that ammonium ions favors primary metabolism, that is, the HMP
      passway and the TCA circle is enhanced, as well as the source of the precursors
      for the biosynthesis of meilingmycin is restricted, which bring about the lower
      production of meilingmycin.

PMID- 15989237
TI  - [Comparative proteomics research on removing of large invasive plasmid pINV of
      Shigella flexneri 2a strain 2457T].
AB  - S. flexneri 2a strain 2457T and its derivative without large invasive plasmid
      pINV-2457T were cultured to middle logarithm phase. Whole cellular protein
      extracts of the two strains were examined by two dimensional (2D) electrophoresis
      using immobilized pH gradient (IPG) technology. After in-gel protein digestion,
      the different-expressed spots were detected by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI TOF MS). All the peptide mass
      fingerprints (PMFs) were searched by the program Mascot developed by Matrix
      Science Ltd. For identifying proteins, databases of S. flexneri 2a 2457T was
      used. Ten proteins with changed expression level were found. Results indicate
      that expression levels of several enzymes involved in nucleic acid metabolism
      have risen, and expression increase of deoxycytidine deaminase, purine nucleoside
      phosphorylase, and uridine nucleoside phosphorylase might lead to increase of
      uridine and uridine nucleoside synthesization.

PMID- 15989238
TI  - [Protein profiling of human dendritic cells infected with mycobacterium
      tuberculosis].
AB  - The response of dendritic cells (DCs) plays an essential role in the initiation
      of immune responses following Mycobacterium tuberculosis (MTB) challenge. Two
      dimensional electrophoresis (2-DE) was employed to compare the global protein
      patterns between human DCs infected and that uninfected with MTB H37Rv ATCC 27294
      strains, and 45 protein spots were found to express differentially. Four protein
      spots which remarkably changed in DCs infected with MTB H37Rv ATCC 27294 strains
      were measured by matrix assisted laser desorption/ionization tandem time-of
      flight (TOF/TOF) mass spectrometry. The data obtained from peptide mass
      fingerprinting were used in protein database search. Four protein spots in gel
      were identified as Human Arsenite-stimulated ATPase (hASNA-I), Annexin IV, gamma
      actin and Heat shock protein27 (HSP27). These data provide insight into the
      changed global protein patterns of the DCs after infection and may prove useful
      for further study in the interaction between MTB and host.

PMID- 15989239
TI  - [The community and structure of nitrogen-fixing microorganism in Sanjiangyuan
      natural reserve].
AB  - Research on the diversity of microorganism community in natural environment has
      been concerned hot spot using the newly molecular biotechnology in the world now.
      To understand the composition and structure of nitrogen-fixing bacteria
      communities in the Qingzang plateau, the molecular diversity and phylogenetic of
      nifH genes of Sangjiangyuan natural reserve were examined by using the PCR-RFLP
      based cloning approach. The 3 samples were come from different sites and
      different plant types, and their biogeochemical parameters were diverse. DNA was
      directly extracted from the soil microorganism and amplified the nifH gene
      fragment using PCR by the primers of nifH-34F 5'-AAAGG(C/T)GG(A/T)
      ATCGG(C/T)AA(A/G) TCCACCAC-3' and nifH-491R 5'
      TFGTT(G/C)GC(G/C)GC(A/G)TACAT(G/C)GCCATCAT-3'. For the nifH gene segment, diverse
      PCR products were characterized by cloning, restriction fragment length
      polymorphism (RFLP) analysis and sequencing. A total of 233 clones and 99
      operational taxonomic units (OTUs) which were digested the clones by the
      restriction enzymes MspI and RsaI were obtained from all samples. YS-1 had 63
      clones and 24 OTUs, ZD-1 had 75 clones and 28 OTUs, and NQ-1 had 95 clones and 47
      OTUs, respectively. They were found 1-2 significant domain groups of clones and
      shared 4 OTUs in all samples. A wide range of sequence divergence was observed in
      the 26 nifH clones that were sequenced from all samples. Sequence comparison
      showed that the nifH clones were 66% to 98% similar. The phylogenetic tree was
      constructed by the Clustal W and Mega software. 26 sequences could be subdivided
      into 4 clusters in the phylogenetic tree, and some of them had the closely
      similar to Proteobacteria, but The majority of the clones were not closely
      related to any known cultivated nitrogen-fixing bacteria, Therefore, most of them
      are unique and may represent novel sequences of nitrogen-fixing bacteria.

PMID- 15989240
TI  - [Relationship among growth temperature, membrane fatty acid composition and
      pressure resistance of Escherichia coli].
AB  - The relationship among growth temperature, membrane fatty acid composition and
      pressure resistance of Escherichia coli was studied. Results indicated that-the
      pressure resistance of exponential-phase cell was maximal in cell growth at 10
      degrees C and decreased with increasing growth temperatures up to 45 degrees C.
      By contrast, the pressure resistance of stationary-phase cell was lowest in cell
      growth at 10 degrees C and increased with increasing growth temperature, reaching
      a maximum at 30 to 37 degrees C before decreasing at 45 degrees C. The proportion
      of unsaturated fatty acids in the membrane lipids decreased with increasing
      growth temperature in both exponential- and stationary-phase cell and correlated
      closely with the melting point of the phospholipids extracted from whole cells.
      Therefore, pressure resistance in exponential-phase cell increased with greater
      membrane fluidity, whereas in stationary-phase cell, there was apparently no
      simple relationship between membrane fluidity and pressure resistance.

PMID- 15989241
TI  - [Effect of glucose on biofilm and the gene ica expression in Staphylococcus
      epidermidis with different biofilm-forming capability].
AB  - The infection of S. epidermidis, an opportunistic human pathogen, depends on
      biofilm formation, and biofilm formation is closely related to environment.
      Researches in the thesis focused on two strains of S. epidermidis with different
      capability of biofilm formation. To find the mechanism of response to environment
      on biofilm formation, biofilm formation and expression of ica, icaR, AtlE in
      theses S. epidermidis cultivated in different grow environment and in media with
      glucose for different time were assayed. Glucose can induce the biofilm formation
      by inducing ica gene, but the inducing do not need continued ica expression, and
      other genes also contribute to the regulation; anti-ODN specially binding icaADBC
      can withstand biofilm inducing from glucose. These results suggest that biofilm
      formation closely related to growth environment, which is a complex regulation
      mechanism. Biofilm formation is closely related to bacteria energy metabolism and
      cell wall synthesis. Some crucial factors in the complex and integrated
      regulation system have not been known yet.

PMID- 15989242
TI  - [Construction of infectious clone of subgroup J avian leukosis virus strain
      NX0101 and its pathogenicity].
AB  - By using PCR, 3 fragments of provirus cDNA of avian leukosis virus (ALV-J) strain
      NXO101 were amplified from the genomic DNA of ALV-J infected cells,and then
      combined in the right direction and sequences into recombinant plasmid pALV-J-NX,
      containing the whole genome of NX0101. After transfection of chicken embryo
      fibroblast (CEF) cells with plasmid pALV-J-NX DNA, the rescued virus was
      identified in CEF by indirect fluorescence antibody test with ALV-J specific
      monoclonal antibody JE9. The rescued virus could replicate in CEF at a titer of
      10(5.6)/mL. The chicken experiment demonstrated that the rescued virus was still
      able to induce tumors in commercial meat-type broilers.

PMID- 15989243
TI  - [Influence of JEV E-HSP70 (Mycobacterium tuberculosis) fusion protein on immune
      response in BALB/c mice].
AB  - JEV infection can cause severe central nerve system disease which result in high
      mortality or developing permanent neurological sequelae in more than half of the
      survivors. The envelope (E) protein of JEV is the major antigen peptide fused to
      it. A recombinant hsp70 protein expression vector pPICZalpha-E-HSP70 in
      methylotrophic yeast Pichia pastoris was developed that permits major antigenic
      segment of JEV E protein fused to the amino terminus of M. tuberculosis hsp70.
      This core vector avoided inclusion bodies formed in Escherichia coli and complex
      purification. Moreover,it ruled out contamination of LPS. Two other vectors
      pPICZalpha-E and pPICZalpha-HSP70 were also constructed. The two vectors were
      constructed by routine molecular technique. All vectors were transformed into
      yeast X-33 by electroporation. Expression of the fusion protein in yeast was
      induced by the addition of methanol every 24 hours and analysed by SDS-PAGE and
      western blot. Major antigenic segment of E protein was produced at a yield of 290
      mg per litter of culture, hsp70 protein at a yield of 178 mg per litter of
      culture and E-HSP70 fusion protein at a yield of 33 mg per litter of culture in
      methylotrophic yeast Pichia pastoris. To examine cell and body immune response
      after BALB/c mice were immunized with E-hsp70 fusion protein expressed in Pichia
      pastoris, there were three groups with ten mice in each group. 5.7 microg
      (50pmol) of E-hsp70 fusion protein, 2.2 microg (50pmol) major antigenic segment
      of E protein and a mixture of hsp70 and major antigenic segment of E protein
      (1:1) including 3.5 microg (50pmol) Hsp70 and 2.2 microg (50pmol) major antigenic
      segment of JEV E protein were used per mouse i.p. on day 0 and day 21. The
      production of mIL-2 was quantitated by semi-quantitative RT-PCR. Besides,
      proliferation of lymphocytes was measured by MTT and titers of antibody was
      determined by ELISA. These data show that the fusion protein is a more powerful
      antigen than major antigenic segment of JEV E protein. So it also illustrates the
      effectiveness of hsp70 in eliciting a humoral and cellular response to an
      attached molecule in the absence of adjuvant and affirms the potential utility of
      hsp70 in vaccine development.

PMID- 15989244
TI  - [Microbial community composition and phylogenetic analysis of deodor biofilter
      under different pH conditions].
AB  - Molecular biological methods were applied to analyze the genetic diversity of
      microbe community in biofilter. V3 variable fragments of genes coding for 16S
      rRNA were amplified by Polymerase Chain Reaction. Then PCR-DGGE combined
      technique were used to analyze the microbial population composition and phylogeny
      of deodorant biofilter. The results indicate that there are prominent differences
      in microbial diversity and abundance between acid and neutral conditions. Owing
      to the selective pressure of extreme acidity, there is less diversity of microbe
      compared with that in neutral environment. It is demonstrated the obvious
      distinction of spacial diversity in different biofilter bed as well. PCR and T
      vector cloning sequencing results shows that the sulfur-oxidizing bacteria are
      the predominant population. The research offers the valid scientific basis for
      better treatment of odorant gas and the theoretical foundation for application of
      bio-deodorization.

PMID- 15989245
TI  - [Construction of the genomic library of Halobacillus sp. D8 and isolation of the
      glycine betaine transporter betH gene].
AB  - Halobacillus sp. D8 is a sporing-forming, gram-positive moderately halophilic
      bacterium which could tolerate up to 25% (W/V) NaCl. A genomic library of
      Halobacillus sp. D8 was constructed using pUC18 as vector, and 9000 recombinant
      plasmids were obtained. By dot blot hybridization, colony PCR and DNA sequencing,
      the entire glycine betaine transporter betH gene was isolated from the
      constructed library. Inspection of the sequenced 4.3 kb DNA region revealed the
      presence of three ORFs. The putative ORF of betH is 1515bp long, encoding a 505
      residue protein (BetH) with a calculated molecular mass of 56.1kD. Hydrophobicity
      plot analysis of BetH indicated a transmembrane protein containing 12
      transmembrane regions. Homology searches for BetH of strain D8 in the GenBank
      using the BLAST program revealed significant sequence identities to other glycine
      betaine transporters: the putative glycine betaine transporter of O. iheyensis
      (64% identity), OpuD of B. subtilis (51% identity), BetH of H. trueperi (49%
      identity), BetL of L. monocytogenes (48% identity), BetM of M. halophilus (43%
      identity) and the putative glycine betaine transporter of B. halodurans (44%
      identity).

PMID- 15989246
TI  - [The expression of gene related to salt tolerance from Sinorhizobium meliloti
      042BM in Escherichia coli and purification of its fusion protein].
AB  - A 1.9kb DNA fragment related to salt tolerance of S. meliloti strain 042BM
      containing two open reading frames were obtained by PCR amplification and ligated
      into shuttle vector pBBR1-MCS2. The complementation experiment showed that ORF2
      is related to salt tolerance and named as rstA gene. Then the gene was cloned
      into the expression vector pThio-HisA, B and C, respectively, and recombinant
      expression vectors pGSA, pGB and pGC were constructed, and transformed into E.
      coli Top10. Inducing by IPTG and analyzing with SDS-PAGE, the fusion protein
      encoded by pGSA was obtained,and it is 36% content of whole cell protein. It was
      isolated and purified by affinity chromography on ProBond, and the inclusion body
      precipitated by saturated sulfate ammonium, and 95% purity of fusion protein was
      obtained. The final product displayed a single band with a corresponding
      molecular weight 43kD in SDS-PAGE, and was verified by the Western blot.

PMID- 15989247
TI  - [Expression and analysis of biological activity of the recombination anthrax
      edema factor].
AB  - Anthrax toxin consists of three separate proteins, protective antigen (PA),
      lethal factor (LF) and edema factor (EF). EF is bacterial adenylate cyclase
      which, upon activation by its eukaryotic cofactor, calmodulin, causes a rapid
      increase in the intracellular cAMP level of host cells. EF can reduce the
      protective ability of host animal. In order to further research the mechanism of
      anthrax toxin, the expression plasmid was constructed and the structural gene for
      anthrax edema factor (EF) was expressed in Escherichia coli. Recombinant EF (rEF)
      was purified to homogeneity by a three-step procedure involving metal chelating
      affinity chromatography, cation-exchange chromatography and gel chromatography.
      From 1 liter of culture, 5mg of biologically active EF was easily purified.
      Rabbits were immuned with rEF, anti-EF antibodies were prepared and can
      neutralize rEF in cells. Tests in vitro proved rEF have good biological activity.
      rEF can competed the binding regions of PA with rLF in J774A.1 and CHO cells. rEF
      and rLF can restrain each other by competition. The successful expression of rEF
      has placed a solid foundation for the research on toxicity mechanism of EF, and
      screening for inhibitors against EF.

PMID- 15989248
TI  - [Characterization and influence factors of Fe(III) reduction of Shewanella cinica
      D14T].
AB  - This is the first time to described the dissimilatory Fe(III) reducing
      characteristics of Shewanella cinica D14T. The effects of O2, light, temperature
      and pH on dissimilatory Fe(III) reduction were examined. The results suggested
      that the rate of Fe(III) reduction decreased with increasing Fe(III)
      concentration. Fe(III) reduction was partially inhibited by the presence of
      either O2 or light. The optimum temperature for Fe(III) reduction is 37 degrees
      C. At pH 6.0-10.0, strain D14T can reduce Fe(III). The soluble Fe(III) is more
      easy to be reduced than the insoluble one. Results of protein denaturants SDS and
      OGP suggest that the Fe(III) reduction activity of S. cinica is mostly localized
      to the soluble outer membrane fraction. The azo dye decolorization and Fe(III)
      reduction in strain D14T were enhanced in the presence of Fe(III) and dye.

PMID- 15989249
TI  - [Analysis of insecticidal crystal proteins from Bacillus thuringiensis strain
      4.0718 through two-dimensional gel electrophoresis and MALDI-TOF-mass
      spectrometry].
AB  - The present study analyses the insecticidal crystal proteins (ICPs) from Bacillus
      thuringiensis strain 4.0718 through two-dimensional electrophoresis and matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS). By comparing and optimizing the composition of lysis solution, the volume of
      sample loading and the protocol for isoelectric focusing, a well-focused 2-DE map
      with high resolution and reproducibility was achieved for the first time. And
      after an tryptic enzymolisis and a test of part of protein spots by means of
      MALDI-TOF-MS, the peptides mass fingerprint (PMF) was obtained and, by referring
      to Swiss-Prot, Cry1Ac and Cry2Aa contained in Bt 4.0718 were identified, with
      their molecular weights 134160 Da and 71097 Da respectively.

PMID- 15989250
TI  - [Research progress of ethanologenic Zymomonas mobilis].
AB  - Zymomonas mobilis is one of the natural ethanologenic microbes. With the unique
      Entner-Doudoroff pathway and some other special pathways of glycolytic and
      energetic metabolism, Z. mobilis has remarkable characters of higher rate of
      ethanol production and higher tolerance to ethanol. Glycolytic and energetic
      metabolism, tolerances (e.g., to ethanol, osmotic stress, etc.) and genetic
      improvements of Z. mobilis are reviewed to elucidate the huge potential of Z.
      mobilis in fuel ethanol production.

PMID- 15989251
TI  - [Ecological interpretation and related strategies for low culturability of
      microorganisms].
AB  - Pure culture technique has been a fundamental method since its invention in
      microbiology, but its isolated and monotonous environment contradicts microbial
      diversity and cooperation relationship in natural environment. And this
      contradiction directly results in the uncultivability of some microbes in media.
      From ecological viewpoint, the recovery barriers of natural microbes mainly
      include the crash of cooperation in natural environment, the great change of
      nutrient in new environment and the loss of native niche. The main methods and
      strategies on low curturability of microorganisms are culture-independent
      methods, enrichment culture, mixed culture, dilution culture, simulating nature
      culture and synthetic method, which can to some degree compensate for the
      traditional approach and improve the low culturability of some bacteria.

PMID- 15989252
TI  - [Bacterial diversity in the sediments of Taihu Lake by using traditional nutrient
      medium and dilution nutrient medium].
AB  - Bacterial diversity in the sediments of Taihu Lake was studied by using
      traditional nutrient medium (NM) and 10-fold dilution of traditional nutrient
      medium (DNM). Results showed that the amount of the bacteria cultured on DNM was
      3-5 times higher of those on NM. The similarities of 16S rRNA gene sequences
      (about 500 bp of 5'-end) of 164 isolates were analyzed. The results indicated
      that the different concentrations of nutrient medium did have effects on the
      dominant bacteria. On traditional nutrient medium, the dominant bacterial groups
      were gamma-Proteobacteria (35.1%), Actinobacteria (24.5%) and Firmicutes (22.3%).
      Most of the bacteria isolated from NM were closely related to genera Pseudomonas,
      Bacillus and Archrobacter. However, the dominant bacterial groups isolated from
      DNM were Actinobacteria (27.1%), Firmicutes (25.7%), alpha-Proteobacteria (21.4%)
      and gamma-Proteobacteria (15.7%). Bacillus-related strains were predominant
      bacteria. The conclusion is that using different concentration media will assist
      to isolate more and comprehensive bacteria from the sediments of Taihu Lake.

PMID- 15989253
TI  - [Molecular diversity and phylogenetic analysis of nitrogen-fixing (nifH) genes in
      alp prairie soil of Sanjiangyuan natural reserve].
AB  - Research on the diversity of microorganism community in natural environment has
      been concerned hot spot using the newly molecular biotechnology in the world now.
      This was the first description of the molecular diversity and phylogenetic
      analysis of nitrogen-fixing (nifH) genes in alp prairie soil of Sanjiangyuan
      natural reserve. DNA was directly extracted from the soil microorganism and
      amplified the nifH gene fragment using PCR by the primers of nifH-34F 5'
      AAAGG(C/T)GG(A/T) ATCGG(C/T)AA(A/G) TCCACCAC-3' and nifH-491R 5'
      TYGTT(G/C)GC(G/C)GC(A/G)TACAT(G/C)G CCATCAT-3'. For the gene fragment, diverse
      PCR products were characterized by cloning, restriction fragment length
      polymorphism (RFLP) analysis and sequencing. 143 clones and 35 different RFLP
      patterns were received in two samples by the restriction enzymes MspI and RsaI
      digested. ZD sample had 82 clones and 21 different RFLP patterns, and YS sample
      had 61 clones and 19 different RFLP patterns. There were shared 5 RFLP patterns
      in two samples. The analysis result found a significant dominant group of clones
      occurring in both samples which account for 29.3% and 32.8%, respectively, and
      several minor groups were also detected. 21 clones were sequenced, and their
      levels of nucleotide identity were from 71% to 98%. None of the sequenced nifH
      gene was completely identical to any deposited in the data banks, and therefore
      each of them belong to a noncharacterized bacterium. Finally, the phylogenetic
      tree was constructed by the Clustal W and Mega software. 21 sequences can be
      subdivided into 4 clusters in the phylogenetic tree, and most of them had the
      closely similar toalpha- , beta-, and gamma-Proteobacteria . The significant
      dominant group in YS sample and ZD sample had the closely related with
      Rhodobacter sphaeroides and Delftia tsuruhatensis, respectively. The YS-nifH-11
      was the only sequence which had highly similar to Cyanobacteria .

PMID- 15989254
TI  - [Identification of a pathogenic strain of locusts and its toxicity and
      pathology].
AB  - A pathogen was isolated from naturally dead grasshoppers. Its pathogenicity was
      testified by law of KOCH. It was identified as Serratia marcescens by
      physiological, biochemical test and molecular systematic analysis. Toxicity of HR
      3 to grasshoppers was assayed by means of oral infection. The results show that
      the linear regression relationship between the logarithm(y) of HR-3 concentration
      and the probability (x) of corrected grasshopper morality is y = 1.067 + 0.809x,
      and the median lethal concentration is LC50 = 1.164 x 10(8) cfu/mLo The infection
      mechanism of HR-3 to grasshoppers were also studied. The histopathological
      studies show that midgut epithelia are damaged at the beginning of infection, and
      then partial denaturalization and putrescence occurr in this area. After 48h
      infection, vacuoles appear in most regions of midgut epithelia.

PMID- 15989255
TI  - [Identification of Vibrio campbellii isolated from cultured pacific oyster].
AB  - Four bacterial strains were isolated from cultured pacific oyster (Crassostrea
      gigia) in September 2003 at coast of Fujian province. Their morphological,
      physiological and biochemical characteristics and 16S rRNA sequence were
      analyzed. And the relationship between reproduction of the bacterium and NaCl
      concentrations, pH and temperature were also determined. The results showed that
      four strains were gram-negative rods with a single polar flagellum, glucose
      fermented without gas production, oxidase positive, required sodium ions for
      growth, no pigment, non-luminescence; They grew well on TCBS-plate as green
      colonies and were sensitive to the vibriostratic agent O/129. Therefore, it was
      confirmed that the strains belonged to the genus of Vibrio. The sequence analysis
      of 16S rRNA gene of SXS1 isolation and comparison with that of other related
      vibrios- showed that SXS1 was very close to Vibrio campbellii. The similarities
      was 99%. The distribution of V. campbellii in environment and its relationship to
      the diseases of aquaculture animals were discussed.

PMID- 15989256
TI  - [Isolation and identification of a strain DN2 degrading nicotine].
AB  - A bacterial strain which was able to utilize nicotine as its sole carbon source
      was isolated from soil in which tobacco had grown at Sanming region in FUjian
      Province and named as DN2. Upon chemotaxonomic characterization and phylogenetic
      inference based 16S rDNA analysis, the strain DN2 was identified as a
      proteobacteria, Ochrobactrum intermedium. For DN2 degrading nicotine, the optimal
      pH and temperature is 6.5, 30 degrees C respectively. It can tolerate high
      concentration of nicotine up to 4000 mg/L in basal media. Using 500 mg/L nicotine
      as its sole carbon, the strain was able to degrade 15 mg/L of nicotine per liter
      per hour and reached its stationary phase in about 36 hours.

PMID- 15989257
TI  - [16S rDNA diversity analysis of 30 Streptomycetes isolates displaying significant
      cytotoxic activity against B16 cell from near-shore sediments of Hainan Island].
AB  - A total of 354 isolates of actinomycetes, of which 76 were detected cytotoxic
      activity was isolated from near-shore marine samples collected at Wenchang
      mangrove, DanZhou harbor and YanPu harbor. Four isolation methods were employed,
      which are SDS pretreatment, phenol pretreatment, heating pretreatment and
      potassium dichromate selection culture, and media such as'Yeast extract-Malt
      extract (YE), Glucose-Asprine (GA), Starch-Casin (SC), Starch-KNO3 (Gause) were
      used. It was showed that heating pretreatment and potassium dichromate selection
      culture were more considerable methods for extensive isolation of actinomycetes.
      Medium YE and Gause showed best results in both the total number of actinomycetes
      and the number of active isolates against tumor cell B16. The genotypic diversity
      of 30 strains of Streptomycetes possessing strong cytotoxic activity against B16
      cell (ID50 > or =200) was analyzed by 16S ARDRA, which resulted in 17 RFLP types,
      and indicated relatively rich genotypic diversity among these Streptomycetes. 16S
      rDNA sequence analysis of three strains, 050642, 060386 and 060524 (ID50 > or =
      1200) further confirmed that they all belong to Streptomyces genus and strain
      050642 was suggested a novel Streptomyces. Spp with the highest similarity of 95%
      to Streptomyces cattleya.

PMID- 15989258
TI  - [Construction and characterization of some virulence determinants-deficient
      strain in Aeromonas hydrophila].
AB  - Cell conjugation was carried out between the donor E. coli CG120 with pAM120
      (Tc(r)/Tn916) and the recipient Aeromonas hydrophila J-1 by filter mating. 3800
      positive clones were gained according to the ability of growth on LB medium with
      10 g/mL tetracycline (Tc) and 100 g/mL cephazolin (cfz). Conjugation efficiency
      was 3 x 10(-5) per donor. When 16S rDNA PCR amplification was performed with
      special primers, positive results were gained in all the 38 conjugants. To
      demonstrate the insertion of Tn916 into the genomes of conjugants, tetracycline
      gene (tet) PCR amplification was performed. A special band could be gained in the
      conjugants with Tc(r). Compared with the parent J-1 strain, some genes of main
      virulence determinants, such as proteases, hemolysins, DNase and amylases, could
      not be expressed in the conjugants. The pathogenicity capability of conjugants
      was greatly decreased and the 50% lethal dose for mice was more than 10(9) CFU.
      By serially passaged for 10 times, the above virulent characters had not been
      regained despite the disappearance of Tc(r). The results showed that by the
      insertion of Tn916, stable and avirulent A. hydrophila mutants could be gained.
      The mechanisms, by which Tn916 induced the changes of virulence characters in A.
      hydrophila, are not definite. It is suspected that there might exist hot spots of
      Tn916 or pathogenicity island on the chronosome of A. hydrophila.

PMID- 15989259
TI  - [Cloning, deletion and functional analysis of noeA from Sinorhizobium meliloti
      042BM].
AB  - 042BM noeA was obtained by PCR. It is identical to that of S. meliloti 1021 at
      99% level, and similarity of their NoeA is 97%. In addition, it was found that
      this protein shares significant homology with the SAM-dependent methyltransferase
      of Mesorhizobium sp. BNC1 (32% similarity), and the similarity of its 303-362
      region to the 160- 220 region of Ll11 methyltransferases of E. coli (PrmA) is
      41%. Compared to 042BM, the noeA deletion mutant 042BMA-Km showed different
      degrees of increase in number of nodule, fresh weight of nodule and plant top dry
      weight on alfalfa cultivars of Putong Zihua, Baoding, Ningxia, Baifa and Aohan,
      but decrease on Milu. However, this mutant has no significant change in ability
      to nodulate cultivars of Huanghou and Zahua. Hence, noeA is involved in alfalfa
      cultivar-specific nodulation.

PMID- 15989260
TI  - [Mangrove soil community analysis using DGGE of 16S rDNA V3 fragment polymerase
      chain reaction products].
AB  - The 16S rDNA V3 fragment polymerase chain reaction products amplified from
      mangrove soil-DNA extracts were analyzed by denaturing gradient gel
      electrophoresis (DGGE) followed by clone technology. Regional factors and
      mangrove species were found to influence the soil microbe community. Two DNA
      slices separated on denaturing gradient gel from Sonneratia alba soil sample were
      recovered and the recovered DNA were used to establish two clone libraries. Some
      clones were sequenced and each sequence was compared with all nucleotide
      sequences in GenBank database. Most cloned sequences were found not in GenBank
      database. These results suggest that DGGE followed by clone technique is a
      practicable protocol to research the complex community of soil microbe.

PMID- 15989261
TI  - [Fusion of betal-toxin gene and beta2-toxin gene from Clostridium perfringens
      type C].
AB  - Betal-toxin and beta2-toxin genes from chromosomal DNA of Clostridium perfringens
      type C were amplified by PCR, PCR products were cleaved with restriction
      endonucleases and recovered. The recombinant plasmid pETXB1-2 containing beta1
      beta2 fusion genes was constructed by recombinant technique and then transformed
      into Escherichia coli BL21 (DE3). The beta1-beta2 fusion proteins were expressed
      in recombinant strain BL21 (DE3) (pETXB1-2), and the expression level of the
      beta1-beta2 fusion proteins was about 15.36% of total cellular protein by SDS
      PAGE and thin-layer gel scanning analysis. More importantly, immunization in a
      mouse model with crude preparation containing the fusion protein inclusion bodies
      or inactivated recombinant strain induced protection against at least 1 MLD of
      the toxin from Clostridium perfringens type C. Hence the fusion proteins possess
      a good immunogenicity. The constructed recombinant strain BL21 (DE3) (pETXB1-2)
      can be used as a candidate of vaccine strain.

PMID- 15989262
TI  - [Coexistence and competition of two satellite RNAs of Cucumber mosaic virus in
      systemic hosts].
AB  - Two Cucumber mosaic virus (CMV) satellite RNAs, namely Yns and Yi and of 385nt
      and 369nt respectively, were introduced to systemic host plants with a satellite
      RNA-free isolate of CMV (CNa), after in vitro transcription of satellite RNAs
      from cDNA clones and by co-inoculation with CMV genomic RNAs. The competition and
      coexistence of the two satellite RNAs were studied by RT-PCR detection, double
      stranded RNA analysis and sequencing comparison. The results showed that, in the
      inoculated leaves of Nicotiana glutinosa, both satellite RNA presented together
      after inoculated 5 days after pseudo-recombination. In the systemic leaves of N.
      glutinosa, both satellite RNAs were detected at 5 days and 10 days post first
      inoculation, however, only the 369nt satellite (Yi) was recovered at 15 days post
      first inoculation and second inoculation transferred from the pseudo
      recombination plants. Comparison of full sequences of the satellite RNAs obtained
      by RT-PCR from pseudo-recombinant virus showed that no mutation and mutual
      exchange of the satellite genome has been found. The results indicate that both
      369nt satellite RNA and 385nt satellite RNA can be introduced to CMV-CNa with in
      vitro transcription products and both replicated to a high level depending on the
      helper virus. But after transferring to new systemic plants, only one satellite
      of 369nt can be kept as co-infection for long with the helper CMV. Co-existence
      and competition are found between different satellite RNAs in the same plant.

PMID- 15989263
TI  - [Construction and immunogenicity of recombinant Canine adenovirus type 2 with the
      external part of glycoprotein of rabies virus].
AB  - The cases of rabies increase greatly in recent years in China and rabies
      continues to be a serious problem in developing countries due to the reservoirs
      of Rabies virus in dogs and wildlife vectors. The control of rabies depends on
      the development of safe, effective, economical vaccines that may be used for
      preexposure vaccination in animals. For this purpose, the external part of
      glycoprotein gene of Rabies virus strain SRV9 (RVG) was amplified by the RT-PCR
      and cloned into pEGFP-C1 with replacement of the GFP gene. The expression
      cassette pERVG2 is composed of CMV promoter, external glycoprotein gene and SV40
      early mRNA polyadenylation signal. The expression cassette was released by Ase I
      /Mlu I double digestion and it was cloned rightwards and leftwards into Canine
      adenovirus type 2(CAV-2) E3 region plasmid pVAXE3 in which E3 region was deleted
      partly by Ssp I /Dra III digestion. After the replacement of CAV-2 E3 region in
      plasmid pCAV-2 which contains CAV-2 genome with the recombinant E3 region,
      recombinant CAV-2 genome plasmid was obtained. Recombinant CAV-2 genome was
      released from plasmid by Asc I /Cla I digestion, and then transfected into MDCK
      cells. Two replication-competent recombinant CAV2 expressing Rabies Virus
      external part of glycoprotein were produced. Vaccination experiment showed that
      the recombinant viruses can elicit an efficient antibody response in dogs.

PMID- 15989264
TI  - [Modification of hybrid antimicrobial peptide CecA-mil gene and its over
      secretion expression in Pichia pastoris].
AB  - According to the partiality codon of Pichia pastoris, hybrid antimicrobial
      peptide CecA-mil gene was reconstructed, synthesized and cloned into pPICZalpha-A
      to construct the recombinant expression vector pPICZa-A-CM. The pPICZalpha-A-CM
      was transformed into yeast host strain X-33. Under the control of the promoter
      AOX1 (alcohol oxidase 1), a approximately 1.9 kD cecA-mil protein was expressed
      with the high level of 245 microg/mL after optimized the requirements for the
      flask-shaking culture fermentation of the Pichia pastoris rX-33/pPICZalpha-A-CM.
      The hybrid antibacterial peptide had a broad spectrum antibacterial activity on
      both gram-positive and gram-negative bacteria, especially showed potent
      antibacterial activity against ampicillin-resistant and kanamycin- resistant
      bacteria, such as Staphylococcus aureus (cowan I) and pathogenic E. coli (O1)
      from chicken. In addition, the hybrid antibacterial peptide showed an extreme
      heat-stable and acid-stable characteristic. Based on these characteristics, the
      recombinant antibacterial peptide CecA-mil display application foreground in the
      field of antisepsis of food, prevention of disease, additives of animal feedstuff
      and so on.

PMID- 15989265
TI  - [Recombinant design and expression of human three-domain antibody against BoNTa].
AB  - VH and Vkappa genes were amplified from human ScFv B17 specific against botulinum
      neurotoxin serotype A (BoNTa). Gene sequence encoding 5'-terminal 12 amino acid
      of heavy chain constant region CH1, as a linker, linked VH and Vkappa to
      construct a new three-domain antibody molecule VH/Vkappa. VH/Vkappa was expressed
      at high level over 34% of total host cell proteins in E. coli. Recombinant
      protein were purified up to 95% by affinity column. As a result, recombinant
      VH/Vkappa could recognize and bind specific to BoNTa in ELISA. However, comparing
      with its parent ScFv, VH/Vkappa has higher relative affinity and stability.

PMID- 15989266
TI  - [Research of restriction display technique in cDNA microarrays preparation for
      detecting of HCV].
AB  - The cDNA microarrays for HCV detection was prepared. With the restriction display
      technique (RD), restriction enzyme Sau3A I was chosen to digest the full-length
      HCV cDNAs. The products were classified and amplified by RD-PCR. We separated the
      differential genes through polyacrylamide gel electrophoresis and sliver
      staining. Single bands were isolated which were cut out from the polyacrylamide
      gel. The third-round PCR could be performed by using the single bands as PCR
      template. The RD-PCR fragments were purified and cloned into the pMD18-T vectors.
      The recombinant plasmids were extracted from positive clones and the target gene
      fragments were sequenced. The cDNA microarray was prepared by spotting PCR
      products to the surface of amido modified glass slides by the robotics. We
      validated the detection of microarray by the hybridization and the results of
      sequence analysis. A total of 24 different cDNA fragments ranging from 200 to 800
      bp were isolated and sequenced, which were the specific gene fragments of HCV.
      These fragments could be further used as probes in the microarray preparations.
      From the results of hybridization and sequence date analysis, the specificity,
      sensitivity, accuracy, reproducibility and linearity in detecting HCV RNA were
      satisfactory. RD technique is of great value in obtaining a large number of size
      comparable gene probes, which provide a swift protocol in generating probes for
      the preparation of microarrays, and the optimized microarray is sensitive and
      effective in clinical diagnosis of HCV.

PMID- 15989267
TI  - [Effects of culture conditions on coenzyme Q10 production by Rhizobium
      radiobacter by metabolic flux analysis].
AB  - Metabolic pathway network of CoQ10 synthesis by R. radiobacter WSH2601 were
      instructed. The metabolic flux and its changes were determined under the
      conditions of changing DO concentration and addition of 1% CSL in the medium. The
      results illustrated that the Ru5P flux (r7) increased by 26.6 when increasing the
      DO concentration, r7 increased by 17.2 when addition of 1% CSL. The ratio of EMP
      and HMP flux as well as TCA flux decreased at these two conditions. DPP flux had
      a little change at these two conditions. Therefore, the CoQ10 accumulation is
      greatly determined by two key enzymes activities of condensation reaction between
      p-hydroxybenzoate acid (PHB) and decaprenyl diphosphate (DPP). The nodes of G6P,
      pyruvate and PEP are principal nodes in primary metabolism of CoQ10 fermentation.
      The flexibility of principal nodes was evaluated that the G6P node is elastic,
      while pyruvate node is weakly flexibility, at the condition of changing culture
      conditions. The increase of DCW is associated with the improvement of HMP pathway
      flux.

PMID- 15989268
TI  - [High-level expression of an extreme-thermostable xylanase B from Thermotoga
      maritima MSB8 in Escherichia coli and Pichia pastoris].
AB  - The family 10 xylanase (XynB) from Thermotoga maritima MSB8 is extremely
      thermostable and great potential in the applications of various fields of
      industry. The gene mxynB(64) was amplified by the method of PCR with the template
      of the genomic DNA of Thermotoga maritima MSB8, and cloned into the expression
      vectors of Escherichia coli and Pichia pastoris respectively. Xylanase B(40kD)
      was successfully expressed by the two heterologous protein expression systems
      with high-level production. The recombinant protein of XynB expressed in Pichia
      pastoris showed extreme thermostability and pH stability, which was optimally
      active at 90 degrees C and quite stable over the pH range of pH 5.0-10.8 at 70
      degrees C. After incubation of the enzyme at 100 degrees C for 30 min, XynB
      retained 70% higher residual activity. The recombinant XynB expressed in Pichia
      pastoris is of great use in a variety of industrial and agricultural
      applications.

PMID- 15989269
TI  - [High expression of alpha-D-galactosidase gene (aga1) of Bifidobacterium breve
      203 in Escherichia coli].
AB  - Alpha-D-galactosidase gene (agal) of Bifidobacterium breve 203 was cloned into
      temperature expression vector pBV220 and transformed into E. coli. The
      recombinant plasmid pBVagal was induced to express with temperature. The specific
      activities of recombinant enzyme Agal in E. coli DH5alpha, E. coli DH10B and E.
      coli BL21 were 28.08 U/mg, 19.44 U/mg and 13.85 U/mg, respectively. The
      recombinant plasmid pBVagal is more stable in E. coli BL21. The molecular weight
      of Agal as determined by SDS-PAGE was about 67 kD. The optimum pH of Agal was pH
      4.0-4.4, and it was stable between pH 3.6 and 6.0 (kept at 4 degrees C
      overnight). The optimum temperature of Agal was 45 degrees C, and it was stable
      below 40 degrees C (incubated for 30 min). Km-values for p-nitrophenyl-alpha
      galactopyranoside (pNPGal) and melibiose were calculated with 1.43 mmol/L and 261
      mmol/L, respectively. No transgalactosylation activity was found when Agal
      hydrolyzed melibiose or raffinose. The results suggest that Agal is much
      different from reported alpha-D-galactosidase from Bi. breve 203. Agal is another
      kind of alpha-D-galactosidase in the same bifidobacteria strain.

PMID- 15989271
TI  - [Cloning and expression in yeasts of the class V chitinase cDNA gene from
      Trichoderma harzianum].
AB  - To explore the integrated bio-control mechanism of Trichoderma harzianum and
      acquire some bio-control associated novel genes, a Trichoderma harzianum mycelium
      cDNA library has been constructed and thereby randomly selected clones were
      sequenced and analyzed by bioinformatics analysis. Full-length cDNA, encoding
      class v chitinase (ChiV), successfully cloned. The results indicated that the ORF
      of ChiV was 1194 bp, encoding 397 aa, deduced molecular weight 44 kD. The gene
      was ligated to the vector of pYES2 and thereby transformed to the yeast of H158
      species. The enzyme activity reached the peak expression after cultured for 60 h
      induced by beta-galactose. The optimal temperature of ChiV is 37 degrees C and
      the optimal pH is 6 and 8.

PMID- 15989270
TI  - [Overexpression of Aspergillus candidus lactase and analysis of enzymatic
      properties].
AB  - The lactase gene lacb' from Aspergillus candidus was fused behind alpha-factor
      signal sequence in the Pichia pastoris expression vector pPIC9, then integrated
      into the genome of P. pastoris by recombination events. The P. pastoris
      recombinants for lactase overexpression were screened by enzyme activity analysis
      and SDS-PAGE. The lactase expressed in P. pastoris was glycosylated protein with
      an apparent molecular weight of 130 kD, while the deglycosylated lactase treated
      with Endo H had an apparent molecular weight of about 110 kD. The expression
      level of secreted lactase protein in recombinant P. pastoris was 6 mg/mL with
      enzymatic activity of 3600 U/mL in the 5 L fermenter, which was the highest among
      that of all kinds of recombinant strains reported now. The optimal pH and optimal
      temperature of the lactase are 5.2 and 60 degrees C. The Vmax, Km, and specific
      activity of the lactase are 3.3 micromol/min, 1.7 mmol/L and 706.5 +/- 2.6 U/mg,
      respectively. Compare to the lactase from Aspergillus oryzae ATCC 20423, the
      expressed lactase from A. candidus have better enzymatic properties including the
      high thermostability, high specific activity and wide pH range for enzyme
      reaction.

PMID- 15989272
TI  - [Identification of psychrotrophs SYP-A2-3 producing cold-adapted protease from
      the No. 1 Glacier of China and study on its fermentation conditions].
AB  - The psychrotrophs SYP-A2-3 producing the cold-adapted protease has been isolated
      from the bacterial samples collected from the No. 1 Glacier of China and
      identified as Bacillus cereus according to its morphological and physiochemical
      characteristics and 16s rDNA gene sequence analysis. It could grow between 0
      degree C and 38 degrees C while its optimal growth temperature was 25 degrees C
      and the optimal temperature for its protease production was 15 degrees C. The
      cold-adapted protease was identified as neutral metallo-protease, the molecular
      weight was 34.2 kD shown by SDS-PAGE, the optimal pH and temperature for activity
      was 7.0-8.5 and 42 degrees C, respectively. Various fermentation conditions of
      its protease production were also investigated. The results showed that casein
      was the best nitrogen source while glucose and starch were suitable carbon source
      for its protease production. The initial pH of fermentation broth ranged from 6.5
      to 7.0 was optimal. Under optimized conditions, the protease activity produced by
      SYP-A2-3 could reach 3800 U/mL and 4800 U/mL conducted in shaking flask and 5 L
      stirred jar experiment, respectively.

PMID- 15989273
TI  - [Characterization of the changes in protease of Deinococcus radiodurans following
      irradiation].
AB  - The activity of protease from Deinococcus radiodurans R1 (DRR1) recovered from UV
      light and gamma-ray irradiation were characterized by SDS-PAGE zymography or FITC
      labeled casein as substrate. It was demonstrated that proteases with large
      molecular weight were abundantly and constitutively expressed in DRR1, which
      consistent with the hypothesis that proteases were among the PHX (predicted
      highly expressed) proteins in DRR1. A broad range of gelatinolytic protease with
      molecular mass more than 140 kD and caseinolytic protease with molecular mass
      more than 120 kD were present in DRR1 cell. The prominent gelatinolytic protease
      of 174 kD was also active when denatured by SDS and displayed different operation
      dynamics during the repair process post UV-irradiation and gamma-irradiation, the
      protease showed its highest activity during gamma-irradiation and in the late
      recovery stage post-irradiation. Some proteases were demonstrated to be induced
      specifically by irradiation which suggests that these proteases may regulate
      breakdown of proteins responsible in sequential pathway, and an elaborate and
      fine tuning protease system may exist in D. radiodurans during the repair process
      post irradiation. The expression of protease was also influenced by the nutrition
      of the culture. A rod-shaped and radiation resistant bacterium RR533.2 isolated
      from soil in Beijing, China was revealed to display similar zymography pattern
      using gelatin or casein as substrate.

PMID- 15989274
TI  - [Purification and properties of a thermostable chitinase from thermophilic fungus
      Thermomyces lanuginosus].
AB  - A thermostable extracellular chitinase from culture supernatant of a thermophilic
      fungus Thermomyces lanuginosus was purified to SDS-PAGE homogeneity, by using
      ammonium sulfate fraction, DEAE-Sepharose Fast flow chromatography, Phenyl
      Sepharose Fast Flow chromatography. A molecular mass of the purified enzyme was
      between 48-49.8 kD determined by SDS-PAGE and gel filtration chromatography. The
      chitinase exhibited optimum catalytic activity at pH 4.5 and 55 degrees C
      respectively. It was thermostable at 50 degrees C and retained 24% activity after
      20 min at 70 degrees C. The half life time of the enzyme at 65 degrees C was 25
      min. Different metal ions showed different effects on the chitinase activity.
      Ca2+, Ba2+, Na+, K+ enhanced the enzyme activity, whereas Fe2+, Ag+, Hg2+, Cu2+
      caused obvious inhibition. The Km and Vmax values of chitinase on colloidal
      chitin were 9.56 mg/mL and 22.12 micromol/min respectively. The chitinase showed
      antifungal activity aginst tested fungi to different degree.

PMID- 15989275
TI  - [Effect of blue light on conidiation development and glucoamylase enhancement in
      Aspergillus niger].
AB  - Pure blue (BL) or red light (RL) were obtained by filtering blue or red
      fluorescent lamp light through plastic filters. With the dark condition as
      control, the effect of BL and RL on the Aspergillus niger were studied including
      soluble protein content of mycelium, glucoamylase activity, the biomass as well
      as sporangiophore photomorphogenesis and vegetative spore development.
      Irradiation with BL and RL wholly promoted glucoamylase activity together with
      the rise of the soluble protein content and the mycelium growth. The glucoamylase
      activity of mycelia culture under blue light was enhanced 2.54 times than that of
      control. In the phases of developmental growth (young mycelia and
      sporangiophores), glucoamylase activity and relative conductivity ratio of
      mycelium were higher under blue light than under dark, the enhanced glucoamylase
      activity likely stemmed from development of macrosporangiophores of Aspergillus
      niger promoted by blue light. In addition, the increase of glucoamylase activity
      under blue light was highest at the stage of macrosporangiophores forming and
      conidiation, then declined owing to spores aging. As to young
      microsporangiophores under darkness the glucoamylase activity just relatively
      increased and declined rapidly with age. Different from control, irradiation with
      blue light at the time of 72 h after inoculation was able to stimulate
      development of macrosporangiophore and conidium along with the rise of
      glucoamylase activity of Aspergillus niger.

PMID- 15989276
TI  - [Effect of exogenous beta-carotene and illumination on sclerotial differentiation
      and carotenoid yield of Penicillium sp. PT95].
AB  - The influence of exogenous beta-carotene and illumination on sclerotial
      differentiation and carotenoid yield of Penicillium sp. PT95 was studied. The
      results showed that in the medium supplemented with exogenous beta-carotene, the
      time of both exudates and sclerotial initials of PT95 strain were delayed. The
      higher the concentration of exogenous beta-carotene was, the longer the time of
      delay. But the time of sclerotial maturation was not changed. On the other hand,
      the exogenous beta-carotene also caused a concentration-dependent reduction of
      both lipid peroxidation and content of carotenoid in sclerotia. The growth
      condition at high (light) oxidative stress favored the sclerotial differentiation
      and pigment accumulation of PT95. The sclerotia biomass and carotenoid yield was
      1.18 and 2.01 fold higher respectively at high than at low (dark) oxidative
      stress. These data revealed that in order to attain higher sclerotia biomass and
      pigment yield, the strain PT95 should be grown under high oxidative stress and in
      the absence of antioxidants.

PMID- 15989277
TI  - [Production and releasing sites of superoxide anion in phytopathogenic bacteria].
AB  - Many phytopathogenic bacteria were founded to release the superoxide anion (O2-)
      by themselves from different sites and the production of O2- was related to the
      pathogenicity of strains. The presences of O2- in cytomembrane, cell wall and
      filtrate were confirmed by chemical method and electron spin resonance (ESR). The
      results show that filtrate may be the primary site of O2- production due to its
      higher O2- generating activity either in the presence or the absence of DDC.
      Additional lines of evidence further suggested a regulatory mechanism of O2-
      production in phytopathogenic bacteria.

PMID- 15989278
TI  - [Cloning of alpha-tubulin gene from Fusarium graminearum and analyzing its
      relationship with carbendazim-resistance].
AB  - The full-length nucleotide sequence of alpha-tubulin gene from each of 6 Fusarium
      graminearum strains from China which had different carbendazim (MBC) sensitivity
      phenotypes were separated using PCR with 4 primer sets designed in accordance
      with nucleotide sequence of the gene from the reference isolate, NRRL 31084 (PH
      1). The DNA sequence comparison showed that there was no difference in the
      nucleotide sequence of alpha-tubulin gene amongst 3 sensitive and 3 resistant
      strains from China. This result demonstrates that there is no relationship
      between MBC-resistance and alpha-tubulin gene. The full-length of the gene spans
      1718 bp, including 6 introns, encoding 449 amino acids. With 99% homology, there
      is 5 nucleotide differences in alpha-tubulin gene between PH-1 isolate and the 6
      strains from China. The homology of the deduced amino acid sequence of the gene
      is 99.78% between the 6 strains and PH-1 isolate, and 37%-86% between the 6
      strains and other 6 species of fungi.

PMID- 15989279
TI  - [Evaluation on the biosafety of classical swine fever DNA vaccine].
AB  - The biosafety of DNA vaccine is one of the key questions which should be solved
      before it is used in the clinical trail. In order to evaluate the biosafety of
      DNA vaccine, the CSFV DNA vaccine was used in the studying target, two main
      aspects of the vaccine were explored in the study. Firstly, the possibility of
      integration of two kinds of DNA vaccine plasmids into pig genome was analyzed by
      PCR technology after the different vaccines were injected through the
      intramuscular introduction. The results showed that both plasmids DNA were
      detected as the form were not integrated into pig genome, it can be detected 30
      copies plasmid DNA in 1 microg total genomic DNA as the sensibility of PCR,
      indicated the safety of the DNA vaccine. Afterward the environmental fecal and
      soil samples in the experimental pens were picked up. Then the antibiotic
      resistant bacteria were isolated and its resistant genes were analyzed by PCR and
      gene sequencing. The results demonstrated that the transfer and spreading of two
      DNA vaccine plasmids studied into environmental bacteria from receptor pigs were
      not found. The results showed that the CSFV DNA vaccine is safe to both pigs and
      the surrounding environment.

PMID- 15989280
TI  - [Cloning and expression of Mycobacterium bovis secreted protein MPB51 in
      Escherichia coli].
AB  - The gene encoding MPB51 was amplified from M. bovis Valleel11 chromosomal DNA
      using PCR technique, and the PCR product was approximately 800 bp DNA segment.
      Using T-A cloning technique, the PCR product was cloned into pGEM-T vector and
      cloning plasmid pGEM-T-51 was thus constructed successfully. pGEM-T-51 and
      pET28a( + ) were digested by BamH I and EcoR I double enzymes. The purified MPB51
      gene was subcloned into the expression vector pET28a( + ), and the prokaryotic
      expression vector pET28a-51 was thus constructed. Plasmid containing pET28a-51
      was transformed into competence E. coli BL21 (DE3). The bacterium was induced by
      IPTG and its lysates were loaded directly onto SDS-PAGE, approximately 30 kD
      exogenous protein was observed on the SDS-PAGE. The protein was analyzed using
      Western blot. The results indicate that the protein is antigenic activity of MB.
      The results are expected to lay foundation for further studies on the subunit
      vaccine and DNA vaccine of MPB51 gene in their prevention of bovine tuberculosis.

PMID- 15989282
TI  - [Two genotypes of Canine coronavirus simultaneously detected in the fecal samples
      of healthy foxes and raccoon dogs].
AB  - 61 fecal samples from healthy foxes and 24 from healthy raccoon dogs were
      examined by RT-nested PCR assays for the presence and genotypic identification of
      Canine coronaviruses (CCVs). 77.0% fox samples were recognized as CCV positive,
      43 of which belonged to type II and 29 to type I, as well as both genotypes were
      simultaneously detected in 25 samples. Out of the total 24 fecal samples from
      raccoon dogs, 22 were CCV positive for type II and 16 for type I. M gene
      fragments of 8 samples were sequenced, 4 of which were confirmed as CCV type I
      and the other 4 as CCV type II. Sequence analysis showed that the M gene of CCV
      type I had a high similarity of 96.7% - 98.1% between the fox-and raccoon dog
      strains and the reported Italian strain from diarrhea dogs. The two genotypes,
      with an identity of 88.3% - 89.7%, formed two separate branches in phylogenetic
      tree. Interestingly, the sequence at several nucleic acid sites of CCV type II
      differed between foxes and raccoon dogs. The co-existence and popularity of the
      two CCV genotypes in healthy foxes and raccoon dogs were first confirmed in this
      article.

PMID- 15989281
TI  - [Tomato R-protein Tm-2(2) gene interacting with ToMV movement protein triggered
      programmed cell death in tobacco transformants].
AB  - Tomato Tm-2(2) and ToMV MP gene are a pair of R-Avr mediated response genes. Tm
      2(2) and MP gene expressed in tobacco transformants with single-copy integration
      respectively. Tm-2(2) transformants displayed virus-resistant specificity as the
      reaction of original Tm-2(2) tomato species in virus-inoculation test. The
      results of agro-infiltration experiment and transformant-crossing test between Tm
      2(2) plants and MP plants indicated that: (1) Tm-2(2) and ToMV-MP maintained
      "Gene for Gene" characters in transgenic tobacco; (2) The interaction between Tm
      22 and MP of ToMV could induce the programmed cell death in the host tobacco by
      exo-ethylene stimulation. This result will be useful in furthering understanding
      of molecular mechanism of Tm-2(2) interaction with ToMV-MP.

PMID- 15989283
TI  - [Preparation of oligosaccharides from alginate by fermenting combined with
      membrane separation method and analysis of the oligomers].
AB  - Changes in biomass, oligosaccharides content and alginate lyase activity in broth
      of Alteromonas sp. incubated in shaking flask and fermentation jar were studied.
      According to those changes, parameters were established for preparing
      oligosaccharides from alginate by fermentation combined with nano-filtration
      membrane separation method. Resulting oligosaccharides were analyzed by gel
      permeation chromatography and thin layer chromatography. One liter culture
      medium(pH 7.5) contains 5 g yeast extract, l0 g peptone, 0.1 g FeSO4, 12 g sodium
      alginate and 1.5 g NaCl. When incubating at 28 degrees C, the result showed that
      the optimal fermentation time was 30 h to obtain the highest production of
      oligosaccharides in the broth. After ultra-filtration and nano-filtration, 94.0%
      of the total oligosaccharides was recovered from the broth, and meanwhile 93.3%
      of the salt was removed. Gel permeation chromatography and TLC analyses indicated
      that the resulting oligosaccharides were composed of five fractions with
      different degree of polymerization.

PMID- 15989284
TI  - [Sterilizing effect of atmospheric pressure plasma jet on microbes].
AB  - To study the sterilizing effect and mechanism of APPJ on microbes preliminarily,
      three representative bacteria, Staphylococcus aureus, Escherichia coli, Bacillus
      subtilis var. niger were treated by two kinds of plasma, DBD (dielectric barrier
      discharge) and APPJ. The survival curves of different microbes were compared and
      analyzed; Furthermore, the morphological change to cell walls and cell membranes
      were studied by scanning electric microscope. These results demonstrated that in
      the beginning phase the sterilizing effect of two kinds of plasmas on three
      microorganisms was stronger than in the later phase, and APPJ was more effective
      than DBD (D value of DBD on Bacillus subtilis var. niger was 70 s, whereas APPJ's
      was 4 s, much more efficient). Meanwhile, the gross morphological damage of E.
      coli cells under SEM after APPJ treatment was observed. These gave the obvious
      evidence that APPJ can destroy the microbes very efficiently, and more likely
      through the damage of cell walls and membranes of microbes treated by APPJ.

PMID- 15989285
TI  - [Progress in the effect of probiotics on cholesterol and its mechanism].
AB  - Because in vitro studies have shown that bacteria can remove cholesterol from
      culture media, much attention has been given to the cholesterol-lowering
      potential of probiotics--especially Lactobacillus and Bifidobacterium, which
      survive passage through the gastrointestinal tract and have beneficial effects on
      the host. Recent research development concerning the in vitro and in vivo
      experimental data were reviewed in this paper, including relationship between
      microbial growth and removal of cholesterol, impact of pH, function of bile
      salts, BSH activities, prebiotics, feeding trial on human beings and animals.
      Moreover, some hypotheses on mechanism of cholesterol removal were discussed,
      such as co-precipitation with bile salts, deconjugation of BSH to bile salts,
      incorporation of cholesterol into the cellular membrane and microbial
      assimilation of cholesterol. In addition, the future research directions and the
      prospect of the probiotics were also viewed.

PMID- 15989286
TI  - Introduction to biostatistics: Part 1. Measurement scales and their summary
      statistics.

PMID- 15989288
TI  - Dalteparin reduced venous thromboembolic events without increased bleeding in
      acutely ill medical patients.

PMID- 15989289
TI  - Review: high-dose vitamin E supplementation is associated with increased all
      cause mortality.

PMID- 15989290
TI  - Rofecoxib increased thrombotic events in patients with colorectal adenomas.

PMID- 15989291
TI  - Celecoxib increased cardiovascular events in patients with colorectal adenomas.

PMID- 15989292
TI  - Reviparin reduced a composite endpoint of death, reinfarction, stroke, and
      ischemia at 7 and 30 days after acute MI.

PMID- 15989293
TI  - A glucose-insulin-potassium infusion did not reduce mortality, cardiac arrest, or
      cardiogenic shock after acute MI.

PMID- 15989294
TI  - An implantable cardioverter-defibrillator but not amiodarone reduced risk for
      death in congestive heart failure.

PMID- 15989295
TI  - Ximelagatran was not inferior to warfarin for preventing stroke and systemic
      embolism in nonvalvular atrial fibrillation.

PMID- 15989296
TI  - Patient self-management of anticoagulants reduced arterial thromboembolism and
      adverse effects.

PMID- 15989297
TI  - Aspirin plus esomeprazole reduced recurrent ulcer bleeding more than clopidogrel
      in high-risk patients.

PMID- 15989298
TI  - Review: dipyridamole given with or without aspirin reduces recurrent stroke.

PMID- 15989299
TI  - Review: population-based screening for abdominal aortic aneurysm reduces cause
      specific mortality in older men.

PMID- 15989300
TI  - Prophylactic coronary artery revascularization before elective vascular surgery
      did not improve long-term survival.

PMID- 15989301
TI  - Review: bisphosphonates are modestly better than placebo for relieving painful
      bone metastases.

PMID- 15989302
TI  - Review: atypical antipsychotic drugs modestly improve neuropsychiatric symptoms
      of dementia.

PMID- 15989303
TI  - Review: little evidence supports the efficacy of major commercial and organized
      self-help weight loss programs.

PMID- 15989304
TI  - Review: somatostatin and its analogues do not reduce mortality in acute bleeding
      esophageal varices.

PMID- 15989305
TI  - Nasogastric and nasojejunal feeding did not differ for acute-phase response or
      pain in severe acute pancreatitis.

PMID- 15989306
TI  - Pegaptanib was effective and safe without a dose-response relation in
      neovascular, age-related, macular degeneration.

PMID- 15989307
TI  - Review: noninvasive positive pressure ventilation reduces intubation and length
      of ICU stay in acute respiratory failure.

PMID- 15989308
TI  - Review: adding long-acting beta2-agonists to inhaled corticosteroids reduces
      asthma exacerbations more than adding antileukotrienes.

PMID- 15989309
TI  - The accuracy of physicians in predicting successful treatment response in
      suspected obstructive sleep apnea did not differ between home monitoring and
      polysomnography.

PMID- 15989310
TI  - Colonoscopy detected colon polyps better than air-contrast barium enema or
      computed tomographic colonography.

PMID- 15989311
TI  - Inhaled corticosteroids did not increase nonvertebral fractures in adults with
      asthma or chronic obstructive pulmonary disease.

PMID- 15989312
TI  - The risk for injury in the elderly may vary by benzodiazepine, independent of
      half-life.

PMID- 15989313
TI  - A risk stratification tool predicted in-hospital mortality in acute decompensated
      heart failure.

PMID- 15989314
TI  - Control of helix formation in vinylogous gamma-peptides by (E)- and (Z)-double
      bonds: a way to ion channels and monomolecular nanotubes.
AB  - [structure: see text] A complete overview on the alternative and competitive
      helices in vinylogous gamma-peptides is given, which was obtained on the basis of
      a systematic conformational analysis at various levels of ab initio MO theory
      (HF/6-31G*, DFT/B3LYP/6-31G*, PCM/HF/6-31G*). Contrary to the parent gamma
      peptides, there is a strict control of helix formation by the configuration of
      the double bond between the C(alpha) and C(beta) atoms of the monomer
      constituents. (E)-Double bonds favor helices with larger pseudocycles beginning
      with 14- up to 27-membered hydrogen-bonded rings, whereas the (Z)-configuration
      of the double bonds supports a distinct preference of helices with smaller seven-
      and nine-membered pseudocycles showing interactions between nearest-neighbor
      peptide bonds. The rather stable helices of the (E)-vinylogous peptides with 22-,
      24-, and 27-membered hydrogen-bonded pseudocycles have inner diameters large
      enough to let molecules or ions pass. Thus, they could be interesting model
      compounds for the design of membrane channels and monomolecular nanotubes. Since
      (E)- and (Z)-vinylogous gamma-amino acids and their oligomers are synthetically
      accessible, our study may stimulate structure research in this novel field of
      foldamers.

PMID- 15989315
TI  - Structure and reactivity of the dammarenyl cation: configurational transmission
      in triterpene synthesis.
AB  - [reaction: see text] The dammarenyl cation (13) is the last common intermediate
      in the cyclization of oxidosqualene to a diverse array of secondary triterpene
      metabolites in plants. We studied the structure and reactivity of 13 to
      understand the factors governing the regio- and stereospecificity of triterpene
      synthesis. First, we demonstrated that 13 has a 17beta side chain in Arabidopsis
      thaliana lupeol synthase (LUP1) by incubating the substrate analogue (18E)-22,23
      dihydro-20-oxaoxidosqualene (21) with LUP1 from a recombinant yeast strain devoid
      of other cyclases and showing that the sole product of 21 was 3beta-hydroxy
      22,23,24,25,26,27-hexanor-17beta-dammaran-20-one. Quantum mechanical calculations
      were carried out on gas-phase models to show that the 20-oxa substitution has
      negligible effect on substrate binding and on the activation energies of
      reactions leading to either C17 epimer of 13. Further molecular modeling
      indicated that, because of limited rotational freedom in the cyclase active site
      cavity, the C17 configuration of the tetracyclic intermediate 13 can be deduced
      from the angular methyl configuration of the pentacyclic or 6-6-6-6 tetracyclic
      product. This rule of configurational transmission aided in elucidating the
      mechanistic pathway accessed by individual cyclases. Grouping of cyclases
      according to mechanistic and taxonomic criteria suggested that the transition
      between pathways involving 17alpha and 17beta intermediates occurred rarely in
      evolutionary history. Two other mechanistic changes were also rare, whereas
      variations on cation rearrangements evolved readily. This perspective furnished
      insights into the phylogenetic relationships of triterpene synthases.

PMID- 15989316
TI  - Asymmetric lithiation-substitution sequences of substituted allylamines.
AB  - [reaction: see text] (-)-Sparteine-mediated asymmetric lithiation-substitution
      sequences of 2- and 3-substituted N-(Boc)-N-(p-methoxyphenyl) allylic amines with
      electrophiles have been investigated. Asymmetric lithiation-substitutions of N
      (Boc)-N-(p-methoxyphenyl) allylic amines 11, 12, 13, 14, and 15 provide highly
      enantioenriched enecarbamates in good yields. Further transformations to give
      aldehydes, acids, ketones, and a Diels-Alder adduct are reported. The 1,4
      addition products from reactions of the lithiated allylic amines from 14 and 15
      with conjugated activated alkenes gives enecarbamates with two and three
      stereogenic centers in good yields with high diastereomeric and enantiomeric
      ratios. Synthetic transformation of these products by acid hydrolysis and
      subsequent cyclization provide stereoselective access to bicyclic compounds
      containing four and five stereogenic centers with high diastereoselectivity and
      enantioselectivity. It is suggested that allyllithium complexes generated by
      asymmetric deprotonation react with most electrophiles with inversion of
      configuration.

PMID- 15989317
TI  - Practical enantioselective synthesis of beta-substituted-beta-amino esters.
AB  - [reaction: see text] A practical, large-scale synthesis of a beta-amino ester 1
      was developed. A chiral imine derived from (S)-phenylglycinol and 3
      trimethylsilylpropanal was coupled with the Reformatsky reagent 3 with high
      diastereoselectivity (de > 98%) to give (SS)-4a as the major isomer. The amino
      alcohol residue of the coupling product 4 was oxidatively cleaved with sodium
      periodate in the presence of methylamine. An unusual selective oxidative cleavage
      of the (SS)-isomer was observed and the imine 6 was obtained with ee > 99% while
      the (RS)-4b isomer was not cleaved. Reaction with p-toluenesulfonic acid
      monohydrate allowed for the hydrolysis of the imine and the isolation of the
      amine as its salt. The title compound 1 was then obtained by transesterification,
      desilylation, and hydrochloride salt formation in a one-pot process. The method
      was successfully applied toward the synthesis of a wide variety of beta-amino
      esters.

PMID- 15989318
TI  - Calix[4]arene-based Zn2+ complexes as shape- and size-selective catalysts of
      ester cleavage.
AB  - [structures: see text] The kinetics of methanolysis of a number of esters endowed
      with a carboxylate anchoring group have been investigated in the presence of di-
      and trinuclear Zn2+ complexes of calix[4]arenes functionalized at the upper rim
      with nitrogen ligands. The results (i) emphasize the importance of a good match
      between ester size and intermetal distance, (ii) reveal a substrate independent
      superiority of the 1,2-vicinal dinuclear catalyst 1-Zn2 to its 1,3-distal
      regioisomer 2-Zn2, and (iii) provide further evidence for the concurrence of the
      three metal ions of 3-Zn3 in the catalytic mechanism.

PMID- 15989319
TI  - Synthesis and structure of cyclopropano-annelated homosesquinorbornene
      derivatives containing pyramidalized double bonds: evidence for the sterical
      effect of a cyclopropyl group on the degree of C=C double-bond pyramidalization.
AB  - [reaction: see text] endo- and exo-2,3,4,7-tetrahydro-1H-1,4
      methanobenzocycloheptene-7-carboxylic acid ethyl esters have been synthesized,
      and their Diels-Alder cycloaddition reactions with maleic anhydride, dimethyl
      acetylenedicarboxylate and singlet oxygen have been investigated. The X-ray
      analysis of four adducts indicated the pyramidalization of the central double
      bond. Density functional theory calculations on the isolated products and model
      compounds showed excellent agreement between the experimental and theoretical
      determined butterfly angles. Furthermore, it has been shown that a cyclopropyl
      group fused to [2.2.2] system decreases significantly the degree of the
      pyramidalization which is attributed to the steric interactions between the
      cyclopropyl group and ethano bridge of the norbornene systems. Due to the
      instability of the bicyclic endoperoxides, their X-ray analysis could not be
      carried out. DFT calculations on model compounds showed increased bending in the
      case of the product obtained by the addition of singlet oxygen to endo-2,3,4,7
      tetrahydro-1H-1,4-methanobenzocycloheptene-7-carboxylic acid ethyl ester.

PMID- 15989320
TI  - Recyclable and reusable Pd(OAc)2/DABCO/PEG-400 system for Suzuki-Miyaura cross
      coupling reaction.
AB  - [reaction: see text] A stable and efficient Pd(OAc)2/DABCO (triethylenediamine)
      catalytic system for Suzuki-Miyaura cross-coupling reaction has been developed.
      In the presence of Pd(OAc)2 and DABCO, coupling of aryl halides with arylboronic
      acids was carried out smoothly to afford good to excellent yields and high
      turnover numbers (TONs) (the maximal TONs were up to 960,000 for the reaction of
      1-iodo-4-nitrobenzene with phenylboronic acid) using PEG-400 as the solvent.
      Moreover, the Pd(OAc)2/DABCO/PEG-400 system could be recycled and reused five
      times without any loss of catalytic activity for aryl iodides and bromides.

PMID- 15989321
TI  - Asymmetric synthesis of 2,4,5-trisubstituted piperidines from sulfinimine-derived
      delta-amino beta-ketoesters. Formal synthesis of pseudodistomin B triacetate.
AB  - [reaction: see text] N-Sulfinyl delta-amino beta-ketoester enaminones, a new
      sulfinimine-derived chiral building block, undergoes, on hydrolysis in one pot,
      an intramolecular Michael addition followed by a retro-Michael-type elimination
      to give enantiopure 2,4,5-trisubstituted piperidines, a structural motif found in
      numerous biologically active alkaloids. This new chiral building block is readily
      prepared by treating N-sulfinyl delta-amino beta-ketoesters with
      dimethylformamide dimethyl acetal. This new protocol was illustrated with a
      concise formal asymmetric synthesis of marine alkaloid pseudodistomin B
      triacetate.

PMID- 15989322
TI  - Simple and efficient methods of synthesis of 3,3-diarylcyclobutanone and 3,3
      diarylcyclobutylamine derivatives using the TiCl4/R3N reagent system.
AB  - [reaction: see text] The iminium ions generated in situ by the oxidation of N,N
      diisopropyl-N-benzylamine using iodine react with diaryl ketones in the presence
      of TiCl4/R3N to give the corresponding 3,3-diarylcyclobutanones in moderate to
      good yields (49-86%). The 3,3-diarylcyclobutanone iminium ions formed in this
      transformation was reduced in situ with B2H6 to produce the corresponding 3,3
      diarylcyclobutylamines (52-79% yields), a class of compounds with potential
      antidepressant activity. In addition, a series of N,N-dimethyl-3,3
      diarylcyclobutylamines were synthesized by the reductive amination of the
      corresponding 3,3-diarylcyclobutanone derivatives.

PMID- 15989323
TI  - Open versus closed 1,3-dipolar additions of C60: a theoretical investigation on
      their mechanism and regioselectivity.
AB  - [reactions: see text] 1,3-Dipolar additions of C60 with dipoles, diazomethane,
      nitrile oxide, and nitrone have been modeled at the B3LYP/6-31G(d,p)//AM1 level,
      and their mechanism, regiochemistry, and nature of addition are investigated. All
      of these reactions lead to the formation of fullerene fused heterocycles;
      theoretically, these reactions can take up four types of additions, viz., closed
      [6,6], open [5,6], closed [5,6], and open [6,6] additions, and all of them have
      been examined. Energetics and thermodynamic analysis of these reactions show that
      closed [5,6] and open [6,6] additions are not probable and that closed [6,6]
      additions are the most favored ones and follow a concerted mechanism.
      Experimental evidence that C60-diazomethane reactions yielded closed [6,6]
      fullerenopyrazoline provides good support to the theoretical predictions. The
      observed order of reactivity has been explained based on the double bond
      character, forcing double bonds in the pentagons of C60, and strain. During the
      addition, dipoles distort more than C60 and concerted closed [6,6] TSs are found
      to be more reactant-like or early TS. Inclusion of toluene as solvent through the
      PCM model increases the reaction rate and exothermicity. NICS values computed at
      the centers of the reacting benzenoid ring of fullerene clearly reveal, in both
      open and closed additions, the loss in them of aromaticity during the reaction.

PMID- 15989324
TI  - 2,5-Dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene: first member of
      the hetero-DuPHOS family.
AB  - [reaction: see text] The 2,5-dimethyl-3,4-bis[(2R,5R)-2,5
      dimethylphospholano]thiophene (UlluPHOS), a new thiophene-based analogue of (R,R)
      1,2-bis(phospholano)benzene (Me-DuPHOS), was synthesized, geometrically and
      electronically characterized, and employed as ligand of Rh and Ru in some
      standard hydrogenation reactions of prostereogenic functionalized carbon-carbon
      and carbon-oxygen double bonds. The synthesis of UlluPHOS is much easier than
      that provided for Me-DuPHOS. UlluPHOS and Me-DuPHOS display very similar
      geometries, while the electronic availability of the former is higher than that
      exhibited by the latter. The Rh and Ru complexes of UlluPHOS produced excellent
      enantiomeric excesses (98.9-99.5%) in the hydrogenation of N-acetyl-alpha-enamino
      acids and reaction rates higher than those found when employing the analogous
      complexes of Me-DuPHOS.

PMID- 15989325
TI  - Toward self-assembled surface-mounted prismatic altitudinal rotors. A test case:
      trigonal and tetragonal prisms.
AB  - [structure: see text] A self-assembly path toward prismatic molecular rotors
      based on transversely reactive terminally metalated molecular rods and pyridine
      terminated star connectors has been extended. The concept has been tested on the
      assembly of trigonal and tetragonal prisms from the biphenyl rod,
      [Ph2P(CH2)3PPh2]Pt+ -C6H4-C6H4-Pt+ [Ph2P(CH2)3PPh2], and the star-shaped
      connectors, 1,3,5-tris(4-ethynylpyridyl)benzene and [tetrakis(4
      pyridyl)cyclobutadiene]cyclopentadienylcobalt, respectively. The prisms have been
      fully characterized by NMR and MS, including diffusion-ordered NMR and collision
      induced dissociation, and their chiral structures optimized by molecular
      mechanics are discussed.

PMID- 15989326
TI  - Total synthesis of polycavernoside A, a lethal toxin of the red alga
      Polycavernosa tsudai.
AB  - [structure: see text] Two approaches to the synthesis of the aglycon 120 of
      polycavernoside A (1) were developed, only one of which was completed. The
      successful "second-generation" route assembled the aglycon seco acids 102 and 106
      via Nozaki-Hiyama-Kishi coupling of aldehyde 70, prepared from methyl (S)-3
      hydroxy-2-methylpropionate (72) and (S)-pantolactone (73), with vinyl bromide 71.
      The latter was obtained from a sequence which commenced from the silyl ether 24
      of 3-hydroxypropionaldehyde and entailed cyclization of (Z)-zeta-hydroxy
      alpha,beta-unsaturated ester 82. Regioselective Yamaguchi lactonization of
      trihydroxycarboxylic acids 102 and 106 and subsequent functional-group
      adjustments led to macrolactone 120, to which the fucopyranosylxylopyranoside
      moiety was attached. Stille coupling of the glycosidated aglycon 128 with
      dienylstannane 129 furnished polycavernoside A in a synthesis for which the
      longest linear sequence was 25 steps. The overall yield to lactone 120 was 4.7%.

PMID- 15989327
TI  - Cubane, cuneane, and their carboxylates: a calorimetric, crystallographic,
      calculational, and conceptual coinvestigation.
AB  - [reaction: see text] This study is a multinational, multidisciplinary
      contribution to the thermochemistry of dimethyl1,4-cubanedicarboxylate and the
      corresponding isomeric, cuneane derivative and provides both structural and
      thermochemical information regarding the rearrangement of dimethyl 1,4
      cubanedicarboxylate to dimethyl 2,6-cuneanedicarboxylate. The enthalpies of
      formation in the condensed phase at T = 298.15 K of dimethyl 1,4
      cubanedicarboxylate (dimethyl pentacyclo[4.2.0.0.(2,5)0.(3,8)0(4,7)]octane-1,4
      dicarboxylate) and dimethyl 2,6-cuneanedicarboxylate (dimethyl
      pentacyclo[3.3.0.0.(2,4)0.(3,7)0(6,8)]octane-2,6-dicarboxylate) have been
      determined by combustion calorimetry, delta(f) H(o)m (cr)/kJ x mol(-1) = -232.62
      +/- 5.84 and -413.02 +/- 5.16, respectively. The enthalpies of sublimation have
      been evaluated by combining vaporization enthalpies evaluated by correlation-gas
      chromatography and fusion enthalpies measured by differential scanning
      calorimetry and adjusted to T = 298.15 K, delta(cr) (g)Hm (298.15 K)/kJ x mol(-1)
      = 117.2 +/- 3.9 and 106.8 +/- 3.0, respectively. Combination of these two
      enthalpies resulted in delta(f) H(o)m (g., 298.15 K)/kJ x mol(-1) of -115.4 +/-
      7.0 for dimethyl 1,4-cubanedicarboxylate and -306.2 +/- 6.0 for dimethyl 2,6
      cuneanedicarboxylate. These measurements, accompanied by quantum chemical
      calculations, resulted in values of delta(f) Hm (g, 298.15 K) = 613.0 +/- 9.5 kJ
      x mol(-1) for cubane and 436.4 +/- 8.8 kJ x mol(-1) for cuneane. From these
      enthalpies of formation, strain enthalpies of 681.0 +/- 9.8 and 504.4 +/- 9.1 kJ
      x mol(-1) were calculated for cubane and cuneane by means of isodesmic reactions,
      respectively. Crystals of dimethyl 2,6-cuneanedicarboxylate are disordered; the
      substitution pattern and structure have been confirmed by determination of the X
      ray crystal structure of the corresponding diacid.

PMID- 15989328
TI  - Oxidative coupling of benzenes with alpha,beta-unsaturated aldehydes by the
      Pd(OAc)2/molybdovanadophosphoric acid/O2 system.
AB  - [reaction: see text] The oxidative coupling reaction of benzene with an
      alpha,beta-unsaturated aldehyde was examined by the combined catalytic system of
      Pd(OAc)2 with molybdovanadophosphoric acid (HPMoV) under atmospheric dioxygen.
      Thus, the reaction of benzene with acrolein under dioxygen (1 atm) by the use of
      catalytic amounts of Pd(OAc)2 and H4PMo11VO40 x 26H2O in the presence of
      dibenzoylmethane as a ligand in propionic acid at 90 degrees C for 1.5 h afforded
      cinnamaldehyde in 59% yield and beta-phenylcinnamaldehyde in 5% yield. This
      catalytic system was extended to the direct oxidative coupling through the C-H
      bond activation of various arenes with acrolein and methacrolein.

PMID- 15989329
TI  - De novo synthesis of stable tetrahydroporphyrinic macrocycles: bacteriochlorins
      and a tetradehydrocorrin.
AB  - [structures: see text] Bacteriochlorins (tetrahydroporphyrins) are attractive for
      diverse photochemical applications owing to their strong absorption in the near
      infrared spectral region, as exemplified by the bacterial photosynthetic pigment
      bacteriochlorophyll a, yet often are labile toward dehydrogenation to give the
      chlorin. Tetradehydrocorrins (ring-contracted tetrahydroporphyrins) are
      attractive for studies of catalysis analogous to that of vitamin B12. An eight
      step synthesis toward such tetrahydroporphyrinic macrocycles begins with p
      tolualdehyde and proceeds to a dihydrodipyrrin-acetal (1) bearing a geminal
      dimethyl group and a p-tolyl substituent. Self-condensation of 1 in CH3CN
      containing BF3 x OEt2 at room temperature afforded a readily separable mixture of
      two free base bacteriochlorins and a free base B,D-tetradehydrocorrin. Each
      bacteriochlorin contains two geminal dimethyl groups to lock-in the
      bacteriochlorin hydrogenation level, p-tolyl substituents at opposing (2,12) beta
      positions, and the absence (H-BC) or presence (MeO-BC) of a methoxy group at the
      5- (meso) position. The B,D-tetradehydrocorrin (TDC) lies equidistant between the
      hydrogenation levels of corrin and corrole, is enantiomeric, and contains two
      geminal dimethyl groups, 2,12-di-p-tolyl substituents, and an acetal group at the
      pyrroline-pyrrole junction. Examination of the effect of the concentrations of 1
      (2.5-50 mM) and BF3 x OEt2 (10-500 mM) revealed a different response surface for
      each of H-BC, MeO-BC, and TDC, enabling relatively selective preparation of a
      given macrocycle. The highest isolated yield of each was 49, 30, and 66%,
      respectively. The macrocycles are stable to routine handling in light and air.
      The bacteriochlorins display characteristic spectral features; for example, H-BC
      exhibits near-IR absorption (lambda(Qy) = 737 nm, epsilon(Qy) = 130,000 M(-1) cm(
      1)) and emission (lambda(em) = 744 nm, phi(f) = 0.14). In summary, this simple
      entry to stable bacteriochlorins and tetradehydrocorrins should facilitate a wide
      variety of applications.

PMID- 15989330
TI  - Roles of C-H...O=S and pi-stacking interactions in the 2-bromoacrolein complex
      with N-tosyl-(S)-tryptophan-derived oxazaborolidinone catalyst.
AB  - [structures: see text] Ab initio and density functional calculations were
      employed to examine the structures and binding energies of various complexes
      between 2-bromolacrolein and N-tosyl-(S)-tryptophan-derived B-butyl-1,3,2
      oxazaborolidin-5-one (NTOB), a catalyst commonly used for Diels-Alder reactions.
      Our calculations show that the chiral oxazaborolidinone catalyst serves as a
      tridentate complexation agent via B...O donor-acceptor, C-H...O hydrogen-bonded,
      and pi-stacking interactions. The most stable complex (1TS) is predicted to have
      a binding energy of -93 kJ mol(-1) (deltaG(298) = -29 kJ mol(-1)). The formyl C
      H...O hydrogen bond and pi-stacking interaction are the key factors governing the
      relative stabilities of the four acrolein-NTOB complexes examined. The calculated
      structure and binding properties of 1TS are consistent with the experimental
      results on the absorption spectrum of the acrolein-NTOB complex and the effects
      of substituents on the reactivity of Diels-Alder reactions. 1TS differs from
      Corey's proposed model of transition-state assembly in two aspects: (1) it
      involves the s-trans-acrolein and (2) it favors a C-H...O interaction via the
      sulfonyl oxygen (C-H...O=S), rather than the ring oxygen (C-H...O-B). This
      calculated structure of the acrolein-catalyst complex provides an alternate
      explanation of the origin of stereoselectivity in the NTOB-catalyzed Diels-Alder
      reactions.

PMID- 15989331
TI  - Development of a third-generation total synthesis of (+)-discodermolide: an
      expedient Still-Gennari-type fragment coupling utilizing an advanced beta
      ketophosphonate.
AB  - [structure: see text] A novel total synthesis of the complex polyketide
      discodermolide, a promising anticancer agent of marine sponge origin, has been
      completed in 11.1% overall yield over 21 linear steps. This third-generation
      approach features an unprecedented Still-Gennari-type HWE olefination reaction
      between advanced C1-C8 beta-ketophosphonate 61 and C9-C24 aldehyde 7, introducing
      the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1-C8
      subunit 61 was established via a highly diastereoselective boron-mediated aldol
      reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)
      configuration was installed by the reduction of enone 73 with K-Selectride.

PMID- 15989332
TI  - Cross-metathesis of C-allyl iminosugars with alkenyl oxazolidines as a key step
      in the synthesis of C-iminoglycosyl alpha-amino acids. A route to iminosugar
      containing C-glycopeptides.
AB  - [structures: see text] A general access to a novel class of sugar alpha-amino
      acids composed of iminofuranose and iminopyranose residues anomerically linked to
      the glycinyl group through an alkyl chain is described. A set of eight compounds
      was prepared by the same reaction sequence involving as an initial step the
      Grubbs Ru-carbene-catalyzed cross-metathesis (CM) of various N-Cbz-protected
      allyl C-iminoglycosides with N-Boc-vinyl- and N-Boc-allyloxazolidine. The
      isolated yields of the CM products (mixtures of E- and Z-alkenes) varied in the
      range 40-70%. Each mixture was elaborated by first reducing the carbon-carbon
      double bond using in situ generated diimide and then unveiling the N-Boc glycinyl
      group [CH(BocNH)CO2H] by oxidative cleavage of the oxazolidine ring by the Jones
      reagent. All amino acids were characterized as their methyl esters. The insertion
      of a model C-iminoglycosyl-2-aminopentanoic acid into a tripeptide via sequential
      carboxylic and amino group coupling with L-phenylalanine derivatives was carried
      out as a demonstration of the potential of these sugar amino acids in designed
      glycopeptide synthesis.

PMID- 15989333
TI  - Catalytic N-sulfonyliminium ion-mediated cyclizations to alpha-vinyl-substituted
      isoquinolines and beta-carbolines and applications in metathesis.
AB  - [reaction: see text] Catalytic Sn(OTf)2-induced cyclization of linear, aryl
      containing allylic N,O-acetals produced vinyl-substituted tetrahydroisoquinolines
      and tetrahydro-1H-beta-carbolines. The usefulness of the vinyl moiety in the
      resulting products was demonstrated via the synthesis of various key building
      blocks for alkaloid structures. The alpha-vinyl moiety was utilized in a [2,3]
      sigmatropic rearrangement, in ring-closing metathesis and a cross-metathesis
      based synthesis of vincantril, an antianoxia agent, and a synthetic member of the
      vincamine type natural products.

PMID- 15989334
TI  - Synthesis of pharmacologically relevant indoles with amine side chains via tandem
      hydroformylation/Fischer indole synthesis.
AB  - [reaction: see text] The sequence of hydroformylation and Fischer indole
      synthesis starting from amino olefins and aryl hydrazines is described. In a
      convergent manner, the two units bearing pharmacologically relevant substituents
      are assembled in the final indolization step. This modular and diversity-oriented
      approach to tryptamines and homotryptamines can be conducted in water and allows
      synthesis of branched and nonbranched tryptamines as well as tryptamine-based
      pharmaceuticals such as the 5-HT1D agonist L 775 606.

PMID- 15989335
TI  - A flexible and versatile strategy for the covalent immobilization of chiral
      catalysts based on pyridinebis(oxazoline) ligands.
AB  - [reaction: see text] Flexible and versatile methods have been developed for the
      immobilization of chiral pyridinebis(oxazoline) ligands by covalent bonding to a
      solid support, either by grafting or by polymerization. Different spacers can
      easily be introduced to modulate the support-ligand distance and the electronic
      properties of the chiral ligand. As an example, 2,6-bis[(S)-4-isopropyloxazolin-2
      yl]pyridine has been immobilized on polystyrene resins, both on a Merrifield-type
      resin by grafting and on supports prepared by polymerization of 4-vinyl
      substituted ligands. The corresponding Ru complexes have been tested as catalysts
      in the cyclopropanation reaction between styrene and ethyl diazoacetate. The
      catalytic activity, the enantioselectivity, and the recyclability are strongly
      dependent on the catalyst preparation method and the total exclusion of oxygen
      and moisture in the filtration process. Under such optimized conditions, yields
      over 60% with up to 90% ee can be obtained in four successive reactions-the best
      cyclopropanation results described to date for a chiral solid ruthenium catalyst.

PMID- 15989336
TI  - Synthesis and properties of novel fluorescent switches.
AB  - [reaction: see text] Photochromic dithienylethene moieties were covalently
      attached to fluorescent 4,4-difluoro-8-(4'-iodophenyl)-1,3,5,7-tetramethyl-4-bora
      3a,4a-diaza-s-indacene (iodo-BODIPY) via a phenylacetylene linker. UV light
      induced isomerization of the photochrome results in significant decrease in
      fluorescence intensity. This fluorescence can be recovered with visible light.
      Steady-state fluorescence measurements demonstrate that the emission of the dye
      can be modulated by external light. An intramolecular energy transfer mechanism
      accounts for the fluorescence quenching in the UV light produced isomers.

PMID- 15989337
TI  - Synthesis and hydrolysis behavior of side-chain functionalized norbornenes.
AB  - [reaction: see text] The stabilities of various functionalized norbornenes that
      are monomers for the ring-opening metathesis polymerization (ROMP) in aqueous
      solution were evaluated toward hydrolysis under a range of temperatures (37, 60,
      and 80 degrees C) and pH values (3-9). All monomers contain hydrolyzable linkages
      to pendant functional groups, and conclusions were drawn relating to how the
      chemical diversity of these pendant functional groups, in accordance with the pH
      and temperature variations, affect hydrolysis of the aforementioned linkages. The
      hydrolysis was monitored by reverse phase HPLC analysis, and/or NMR spectroscopy.
      As expected, monomers containing ester linkages were fairly labile at higher pH
      values, while acetal-based linkers were cleaved at lower pH values. Beta-amino
      ester groups experienced a significant increase in hydrolysis rate, while
      carboxylic acid-containing monomers did not follow any clear trend. Saccharide
      containing monomers exhibited unique behaviors for various pH values and
      temperature ranges.

PMID- 15989338
TI  - Intramolecular Diels-Alder reactions of ester-linked 1,3,8-nonatrienes.
AB  - [structures: see text] Penta-1,3-dienyl acrylates undergo kinetically controlled
      intramolecular Diels-Alder (IMDA) reactions and DFT calculations (B3LYP/6
      31+G(d)) predict stereoselectivities that are in very good agreement with the
      experimental values. The nature of the diene C1 substituent has virtually no
      influence upon reactivity or trans/cis-stereoselectivity whereas terminal C9
      dienophile substituents have a substantial effect on both the reactivity and
      stereoselectivity of these IMDA reactions. The TSs highlight contributions from
      strain in the developing tether-containing ring, and steric and electronic
      effects between tether and dienophile substituents, thus providing insight into
      the origins of IMDA reactivity and stereoselectivity.

PMID- 15989339
TI  - A modular synthesis of unsymmetrical tetraarylazadipyrromethenes.
AB  - [reaction: see text] A stepwise route to unsymmetrical
      tetraarylazadipyrromethenes by a condensation of 2,4-diaryl-5-nitroso-pyrroles
      with 2,4-diarylpyrroles is described. This modular building-block approach allows
      for the introduction of up to four different aryl substituents on the
      azadipyrromethene and is tolerant of a varied substituent set. An efficient
      synthesis of the 2,4-diarylpyrroles building blocks from 1,3-diaryl-4-nitro-butan
      1-ones by nitro hydrolysis to a keto-aldehyde and subsequent ammonia condensation
      reaction has been achieved. The facile conversion of 2,4-diarylpyrroles into
      their alpha-nitroso analogues by their reaction with sodium nitrite generated the
      second building block required for the synthesis.

PMID- 15989340
TI  - Ester dienolate [2,3]-Wittig rearrangement in natural product synthesis:
      diastereoselective total synthesis of the triester of viridiofungin A, A2, and
      A4.
AB  - [structure: see text] An ester dienolate [2,3]-Wittig rearrangement was utilized
      to access the alkylated citric acid skeleton 6 that is characteristic for the
      viridiofungins and other members of the alkyl citrate family of secondary natural
      products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the
      rearrangement product (+/-)-syn-16 in moderate yield and with very good
      diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect
      the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the
      viridiofungins. Amide formation between the racemic viridiofungin precursors 35a
      c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by
      preparative reversed-phase HPLC provided the isopropyl dimethyl ester of
      viridiofungin A ((+)-39a), A2 ((+)-39b), and A4 ((+)-39c) as well as the
      nonnatural diastereomers (-)-38a-c.

PMID- 15989341
TI  - Tetracyanoanthraquinodimethanes with a chiral amide group: preparation,
      properties, and charge-transfer photochirogenetic reaction with 1,2
      dianisylacenaphthene-1,2-diol.
AB  - [reaction: see text] A series of butterfly-shaped tetracyanoanthraquinodimethanes
      (TCNAQs) with a chiral amide auxiliary 1a-f were prepared from the corresponding
      anthraquinones. They are stronger acceptors than the unsubstituted derivative and
      undergo one-wave two-electron reduction. They form weak electron-donor-acceptor
      (EDA) complexes with the title pinacol 2. Upon charge-transfer excitation of
      these complexes, dihydro-TCNAQs 3 and 1,8-dianisoylnaphthalene 4 were efficiently
      formed, the latter of which is the product of a retropinacol reaction via 2+*.
      Partial enantiodifferentiation of rac-2 was realized during the photoreactions
      with 2-[(R)-1-phenylethylcarbamoyl]-TCNAQ 1ain CD3CN. Thus, optically active
      (S,S)-(+)-pinacol 2 (12.3% ee at 54% conversion; 21.5% ee at 70% conversion) was
      recovered from the photolyzates. This reaction represents a new and rare example
      of the pseudokinetic resolution of tert-alcohol accompanied by C-C bond fission.
      Significant differences in the association constants for the diastereomeric EDA
      complexes are responsible for the observed enantiodifferentiation.

PMID- 15989342
TI  - Synthesis of mono- and dihydroxylated furanoses, pyranoses, and an oxepanose for
      the preparation of natural product analogue libraries.
AB  - [structures: see text] Numerous biologically active natural products contain
      furanoses and pyranoses with mono- and dihydroxylated substituents. However, much
      of the structure-activity studies on such molecules is gathered on the aglycons
      without attention to the corresponding carbohydrate components. Consequently,
      there are few synthetic procedures that enable the rapid preparation of mono- and
      dihydroxyfuranoses and mono- and dihydroxypyranoses and no report for a 3,4
      dihydroxyoxepanose. In this article we report the practical synthesis of
      orthogonally protected five-, six-, and seven-membered carbohydrate derivatives.
      The succinct manner in which these molecules were synthesized allows the rapid
      preparation of analogues aimed at discovering the role of ring size and
      individual hydroxyl moieties on the pyranose skeleton.

PMID- 15989343
TI  - Palladium-catalyzed isomerization of methylenecyclopropanes in acetic acid.
AB  - [reaction: see text] Pd(PPh3)4-catalyzed isomerization of MCPs 1 in acetic acid
      proceeds smoothly at 80 degrees C in toluene to give the corresponding 1
      substituted or 1,1-disubstituted dienes 2 in good to excellent yields under mild
      conditions. The plausible mechanism has been disclosed on the basis of a
      deuterium-labeling experiment.

PMID- 15989344
TI  - Phosphinoselenothioic acids and their salts: synthesis, characterization, and
      reaction with electrophiles.
AB  - [reaction: see text] Phosphinoselenothioic acid ammonium salts were synthesized
      in good yields by reacting phosphinoselenothioic acid S-[2-(trimethylsilyl)ethyl]
      esters with ammonium fluorides. Phosphinoselenothioic acid alkali metal salts
      were obtained as 18-crown-6 ether complexes with high efficiency by treating the
      esters with alkali metal fluorides and 18-crown-6 ether. The salts were stable
      under air and soluble in water. The structures of the phosphinoselenothioic acid
      tetramethylammonium salt and P-methylseleno-P-methylthiophosphonium triflate were
      determined by X-ray molecular structure analyses. These salts exhibited monomeric
      structures, and the central phosphorus atoms adopted tetrahedral structures.
      Alkylation of the ammonium salts selectively gave phosphinoselenothioic acid Se
      alkyl esters, whereas acylation of the salts preferentially gave S-acyl products.
      Protonation of the salts selectively gave the phosphinoselenothioic S-acid. The S
      acid generated in situ was reacted with alpha,beta-unsaturated carbonyl compounds
      and cyclohexene oxide to give the adducts. Molecular orbital calculations were
      carried out for the model compound H2P(Se)S- to elucidate the electronic
      structure.

PMID- 15989345
TI  - Pyridinium salt photochemistry in a concise route for synthesis of the trehazolin
      aminocyclitol, trehazolamine.
AB  - [reaction: see text] A strategy for the concise synthesis of trehazolamine, the
      aminocyclitol core of the potent trehalase inhibitor trehazolin, has been
      developed. The methodology takes advantage of photocyclization reaction of 1
      methoxyethoxymethyl-3-pivaloxymethylpyridinium perchlorate to generate a bicyclic
      aziridine intermediate, which is transformed under aziridine ring opening
      conditions to the key intermediate, 3,5-diacetoxy-3-pivaloxymethyl-4-(N
      acetylamino)cyclopentene. In addition, the strategy is used in an enantio
      divergent sequence for preparation of the natural (+)-trehazolamine and its
      unnatural (-)-enantiomer. In this route, the chiral auxiliary containing 1
      (tetracetyl-alpha-D-glucosyl)-3-pivaloxymethylpyridinium perchlorate undergoes
      photocyclization to generate separable, diastereomeric bicyclic-aziridines, which
      are then independently transformed to enantiomeric 3,5-diacetoxy-3-pivaloxymethyl
      4-(N-acetylamino)cyclopentenes.

PMID- 15989346
TI  - Aminolysis of aryl N-ethyl thionocarbamates: cooperative effects of atom pairs O
      and S on the reactivity and mechanism.
AB  - [reaction: see text] The aminolysis reactions of aryl N-ethyl thionocarbamates
      (ETNC/EtHN-C(=S)-OC6H4Z) with benzylamines (XC6H4CH2NH2) in acetonitrile are
      investigated at 30.0 degrees C. The rate of ETNC is slower by a factor of ca. 3
      than the corresponding aminolysis of aryl N-ethyl thiocarbamate (AETC/EtHN-(C=O)
      SC6H4Z), which has been interpreted in terms of cooperative effects of atom pairs
      O and S on the reactivity and mechanism. For concerted processes, these effects
      predict a rate sequence, -C(=S)-S- < -C(=S)-O- < -C-(=O)-S- < -C-(=O)-O-, and the
      present results are consistent with this order. The negative cross-interaction
      constant, rho(XZ) = -0.87, the magnitude of betaZ (= 0.36-0.50) and failure of
      the RSP are in accord with the concerted mechanism. The normal kinetic isotope
      effects, kH/kD = 1.52-1.78, involving deuterated benzylamines suggest a hydrogen
      bonded cyclic transition state. Other factors influencing the mechanism are also
      discussed.

PMID- 15989347
TI  - Selective synthesis of allylated oxime ethers and nitrones based on palladium
      catalyzed allylic substitution of oximes.
AB  - [reaction: see text] The viability of oximes as nucleophiles in transition-metal
      catalyzed allylic substitution was examined. The oxygen atom of oxime acted as a
      reactive nucleophile in the reaction of a pi-allyl palladium complex. In the
      presence of Pd(PPh3)4, the allylic substitution of oximes with allylic carbonate
      afforded the linear O-allylated oxime ethers selectively without a base. In
      contrast, the palladium-catalyzed reaction with allylic acetate proceeded
      smoothly in the presence of K2CO3 or Et2Zn as a base. Selective formation of
      nitrones was achieved by using palladium(II) catalyst. In the presence of
      Pd(cod)Cl2, the allylic substitution of oximes with allylic acetate afforded the
      N-allylated nitrones under solvent-free conditions, as a result of the reaction
      with the nitrogen atom of oximes.

PMID- 15989348
TI  - Two-step metal-mediated transformation of isoxazolidine-5-spirocyclopropanes into
      pyridone derivatives.
AB  - [reaction: see text] The two-step metal-catalyzed overall transformation of
      isoxazolidine-5-spirocyclopropanes into the corresponding dihydro- and
      tetrahydropyridones is described. The first step is the chemoselective reduction
      of the N-O bond of the isoxazolidine ring preserving the fragile cyclopropanol
      moiety while the second transformation is the Pd(II) or Pd(0) conversion of the
      beta-aminocyclopropanol derivatives into the final compounds. The scope and
      limitations of this strategy are described.

PMID- 15989349
TI  - First asymmetric total synthesis of synerazol, an antifungal antibiotic, and
      determination of its absolute stereochemistry.
AB  - [reaction: see text] By synthesizing two possible diastereomers, the first
      asymmetric total synthesis of synerazol, an antifungal antibiotic, has been
      accomplished, allowing determination of its absolute stereochemistry. A more
      practical second generation route was also established. The key steps are
      racemization-free deprotection of a TIPS group and introduction of a methyl ether
      by DMD oxidation of the benzylidene moiety in a substrate having a small
      protecting group.

PMID- 15989350
TI  - Stereoselective synthesis of beta-anomeric 4'-thiaspirocyclic ribonucleosides
      carrying the full complement of RNA-level hydroxyl substitution.
AB  - [reaction: see text] Stereoselective syntheses of a group of 4'-thiaspirocyclic
      ribonucleosides featuring both pyrimidine and purine classes and both possible
      configurations at C-5' are described. Use is made of the Pummerer reaction of
      substrates carrying an alpha-oriented 2,4-dimethoxybenzoyloxy substituent at C-2
      in order to gain reliable stereocontrol via neighboring group participation.
      Irrespective of the S or R configuration of the pivotal sulfoxide intermediates,
      the nucleobase is captured from the beta-face. The competing process is formation
      of unsaturated sulfoxides, presumably via competing E2-type elimination. Although
      differences in reactivity between the two stereoisomeric series were noted, the
      common route has successfully given rise for the first time to desirable beta
      anomeric sulfur-containing spiroribonucleosides with minimum formation of the
      alpha-anomers.

PMID- 15989351
TI  - An asymmetric nitro-Mannich reaction applicable to alkyl, aryl, and heterocyclic
      imines.
AB  - [reaction: see text] A protocol for the enantioselective nitro-Mannich coupling
      between alkyl, aryl, and heterocyclic p-methoxybenzylimines and
      trimethylsilylnitropropanate catalyzed by a chiral tBu-BOX Cu(II) catalyst is
      described. It uses the lowest reported loading of commercially available metal
      catalyst and chiral ligand, and gives the highest yields and selectivities for a
      broad substrate range including nonaromatic aldimines. The resultant beta
      nitroamines are obtained in 70-94% enantiomeric excess in good yield and can be
      readily reduced to synthetically useful 1,2-diamines.

PMID- 15989352
TI  - Theoretical and experimental investigation of the basicity of
      phosphino(silyl)carbenes.
AB  - [reaction: see text] The reactivity of phosphino(trimethylsilyl)carbenes 1 with
      several organic acids has been examined in order to evaluate the pKa values of
      the conjugate acids. Carbenes 1 react efficiently with C-organic acids such as
      1,3-dimesitylimidazolium chloride, phenylacetylene, acetonitrile, and
      acetyltrimethylsilane, which have pKa's in DMSO in the range 18-31. However, the
      reaction of the conjugate acids 1H+ with the anion perturbs the determination of
      the genuine basicity of 1. Theoretical calculations have been performed in order
      to quantify the basicity of phosphino(trimethylsilyl)carbenes 1 and to compare
      them with that of N-heterocyclic carbenes 2. The pKa of 1H+ in DMSO has been
      computed to be in the 23.0-23.4 range, so that 1 is not strong enough as a base
      to spontaneously deprotonate organic acids such as phenylacetylene, acetonitrile,
      or acetyltrimethylsilane. However, its conjugate acid 1H+ is a strong
      electrophile and easily reacts with the nucleophilic conjugate bases of these
      acids leading to the formation of the corresponding phosphorus ylides.

PMID- 15989353
TI  - Direct, facile aldehyde and ketone alpha-selenenylation reactions promoted by L
      prolinamide and pyrrolidine sulfonamide organocatalysts.
AB  - [reaction: see text] A new catalytic method for direct alpha-selenenylation
      reactions of aldehydes and ketones has been developed. The results of exploratory
      studies have demonstrated that L-prolinamide is an effective catalyst for alpha
      selenenylation reactions of aldehydes, whereas pyrrolidine
      trifluoromethanesulfonamide efficiently promotes reactions of ketones. Under
      optimized reaction conditions, using N-(phenylseleno)phthalimide as the
      selenenylation reagent in CH2Cl2 in the presence of L-prolinamide (2 mol %) or
      pyrrolidine trifluoromethanesulfonamide (10 mol %), a variety of aldehydes and
      ketones undergo this process to generate alpha-selenenylation products in high
      yields. Mechanistic insight into the L-proline and L-prolinamide catalyzed alpha
      selenenylation reactions of aldehydes with N-(phenylseleno)phthalimide has come
      from theoretical studies employing ab initio methods and density functional
      theory. The results reveal that (1) the rate-limiting step of the process
      involves attack of the enamine intermediate at selenium in N
      (phenylseleno)phthalimide and (2) the energy of the transition state for the
      reaction catalyzed by prolinamide is lower than that promoted by proline. This
      result is consistent with experimental observations. The role of hydrogen bond
      interactions in stabilizing the transition states for this process is also
      discussed.

PMID- 15989354
TI  - Total synthesis of pinnamine and anatoxin-a via a common intermediate. A caveat
      on the anatoxin-a endgame.
AB  - [reaction: see text] This paper describes the total synthesis of the naturally
      occurring alkaloids pinnamine (1) and anatoxin-a (2) from a common
      enantiomerically pure intermediate (7) easily available from pyroglutamic acid.
      The synthesis of enantiopure pinnamine proceeded in 10 steps and 4.8% overall
      yield, and the route was flexible enough to allow stereocontrolled access to a
      non-natural congener (5-epi-pinnamine) of the natural product. Intramolecular
      reaction of an N-acyl iminium ion was a key step in the synthesis of both
      pinnamine and anatoxin-a. However, in stark contrast to literature precedent,
      complete racemization was observed during the reaction of the N-acyliminium ion
      leading to the latter alkaloid.

PMID- 15989355
TI  - Functionalized [3 + 3]cycloalkynes: substituent effect on self-aggregation by
      nonplanar pi-pi interactions.
AB  - [reaction: see text] Optically active (M)-2,11-dihydroxy-1,12
      dimethylbenzo[c]phenanthrene-5,8-dicarbonitrile was synthesized from (M)-1,12
      dimethyl-2,11-dinitrobenzo[c]phenanthrene-5,8-dicarbonitrile by the reduction and
      hydroxylation of nitro groups. The compound was converted to several oxygen
      functionalized [3 + 3]cycloalkynes with -OH, -OSiMe2-t-Bu, -OAc, -OTf, or -ONf
      groups, which are chiral arylene ethynylene macrocycles containing three
      helicenes. The aggregation behaviors of these [3 + 3]cycloalkynes were examined
      in CHCl3, THF, and acetone using 1H NMR, CD, and vapor pressure osmometry (VPO)
      studies and were compared with that of the parent [3 + 3]cycloalkyne. An
      increasing strength of aggregation in CHCl3 was observed in the following order
      of the substituted derivatives: -H > -ONf > -OTf > -OAc > -OSiMe2-t-Bu. In THF
      the following strength of aggregation was observed: -OTf > -ONf > -OAc > -H > 
      OSiMe(2)-t-Bu > -OH. The aggregation of the functionalized [3 + 3]cycloalkynes is
      stronger for the compounds with electron-withdrawing substituents than for those
      with electron-donating substituents. (M)-1,12-dimethylbenzo[c]phenanthrene
      2,5,8,11-tetraol was also synthesized from the same intermediate. This electron
      rich helicene was readily oxidized to 5,6-quinone in air, and the quinone was
      suggested to form a self-charge-transfer complex in solid state.

PMID- 15989356
TI  - Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase
      A.
AB  - [structure: see text] Matrix metalloproteinases (MMPs), of which 26 are known,
      have been implicated in a number of pathological conditions, including tumor
      metastasis. We have previously described the first mechanism-based inhibitor for
      MMPs (J. Am. Chem. Soc. 2000, 122, 6799-6800), which in chemistry mediated by the
      active site zinc ion selectively and covalently inhibits MMP-2, -3, and -9.
      Computational analyses indicated that this selectivity in inhibition of MMPs
      could be improved by design of new variants of the inhibitor class. We report
      herein the syntheses of methyl 2-(4-{4-[(2
      thiiranylpropyl)sulfonyl]phenoxy}phenyl)acetate (3) and 2-(4-{4-[(2
      thiiranylpropyl)sulfonyl]phenoxy}phenyl)acetic acid (4), and show that compound 3
      serves as a mechanism-based inhibitor exclusively for MMP-2. This molecule should
      prove useful in delineating the functions of MMP-2 in biological systems.

PMID- 15989357
TI  - X-ray quality geometries of geodesic polyarenes from theoretical calculations:
      what levels of theory are reliable?
AB  - [structure: see text] Computational methods for calculating molecular geometries
      have not been well calibrated heretofore against X-ray data for bowl-shaped
      polycyclic aromatic hydrocarbons (PAHs). The analysis presented here capitalizes
      on a rare opportunity provided by corannulene to account explicitly for molecular
      distortions from crystal packing forces. Within the error limits of an extensive
      X-ray data set, B3LYP/6-31G* calculations were found to correctly reproduce all
      of the experimental bond distances and bond angles. The reliability and
      shortcomings of geometry calculations at other levels of theory are enumerated.

PMID- 15989358
TI  - Why, on interaction of urea-based receptors with fluoride, beautiful colors
      develop.
AB  - [reaction: see text] Urea-based receptors, containing electron-withdrawing
      chromogenic substituents, in a DMSO solution, in the presence of varying excess
      of fluoride, do not form H-bond complexes, but undergo stepwise deprotonation of
      the two N-H fragments, an event which is signaled by the development of vivid
      colors. Double deprotonation is also observed in the presence of hydroxide. Less
      basic anions (CH3COO-, H2PO4-) induce deprotonation of only one N-H.

PMID- 15989359
TI  - A convenient enantioselective synthesis of (S)-alpha-trifluoromethylisoserine.
AB  - [reaction: see text] This report describes two straightforward synthetic
      methodologies to obtain alpha-CF3-isoserine, a new alpha,alpha-disubstituted beta
      amino acid, from alpha-(trifluoromethyl)acrylic acid. The routes involve the
      synthesis of five-membered cyclic sulfates (using sulfuryl chloride) or
      sulfamidates (using the Burgess reagent) from the corresponding chiral diols,
      which are obtained by a catalytic asymmetric dihydroxylation (AD) reaction.

PMID- 15989360
TI  - An efficient synthesis of achiral and chiral 1,2,4-triazolium salts: bench stable
      precursors for N-heterocyclic carbenes.
AB  - [reaction: see text] The promising utility of triazolyl N-heterocyclic carbene
      catalysts in umpolung aldehyde chemistry requires a straightforward reliable
      synthesis from readily available materials. Herein, we describe the synthesis of
      a variety of triazolyl N-heterocyclic carbene precursors. The reactions commence
      from commercially available amino acids and proceed in 44-68% overall yields. The
      N-heterocyclic salts are air-stable crystalline solids that can be stored with no
      special precaution and can generate the active catalyst when treated with an
      appropriate base.

PMID- 15989361
TI  - A new saccharide sensor based on a tetrathiafulvalene-anthracene dyad with a
      boronic acid group.
AB  - [reaction: see text] A new saccharide sensor based on a tetrathiafulvalene
      anthracene dyad with a boronic acid group was designed and synthesized. Our study
      employed the tetrathiafulvalene (TTF) unit as the electron-rich group in the
      saccharide sensor instead of an amine group, and this new sensor detects fructose
      with good selectivity.

PMID- 15989362
TI  - Me2Zn-mediated addition of acetylenes to aldehydes and ketones.
AB  - [reaction: see text] Contrary to expectations, commercially available 2 M Me2Zn
      in toluene is able to promote the addition of phenylacetylene to aldehydes and
      ketones. This reactivity is determined by a new, unprecedented mechanism, which
      involves activation of the zinc reagent via coordination with carbonyl substrates
      that behave "ligand like". Broad scope, high tolerance to functional groups, and
      a simple procedure make this new method highly interesting for the synthetic
      chemist.

PMID- 15989363
TI  - Convenient synthesis of oxazolidinones by the use of halomethyloxirane, primary
      amine, and carbonate salt.
AB  - [reaction: see text] Primary amines reacted with carbonate salts (Na2CO3, K2CO3,
      Cs2CO3, and Ag2CO3) and halomethyloxiranes in the presence of a base such as DBU
      or TEA to give oxazolidinones in high yields. The use of K2CO3 among these
      carbonate gave the best yield in this synthesis. A reaction mechanism was
      proposed that the oxazolidinone was obtained from an oxazinanone intermediate via
      a bicyclo[2.2.1] intermediate. The present reaction can be widely applied to
      convenient synthesis of useful N-substituted oxazolidinones and chiral
      oxazolidinones.

PMID- 15989364
TI  - A convenient route to diverse heterocycles through an addition of beta-amino
      carbonyl compounds to 3-halogeno-4-methoxybenzynes.
AB  - [reaction: see text] 3-Halogeno-4-methoxybenzynes 5 generated from 5-(3-halogeno
      4-methoxyphenyl)thianthrenium perchlorates 1 and LDA in THF at reflux reacted
      with various beta-amino carbonyl compounds and 2-aminophenyl benzenesulfonate
      etc. to give diverse heterocyclic compounds.

PMID- 15989365
TI  - New highly nucleophilic and practically accessible chlorocarbenoids for carbonyl
      olefination.
AB  - [reaction: see text] Direct oxidative addition of CHCl3 to the Mg-TiCl4
      bimetallic species resulted in the generation of a highly nucleophilic and
      practically convenient chloromethylenetitanium complex, which efficiently
      effected condensation even with enolizable or inert carbonyl compounds, such as
      sterically congested ketones, to provide vinyl chloride compounds.

PMID- 15989366
TI  - Synthesis and NMR studies on a C3-symmetrical triquinolina triscationic
      bicyclophane.
AB  - [structure: see text] Two-step syntheses of triple-bridged triscationic
      bicyclophanes are presented. Molecular modeling has been undertaken by means of
      ab initio calculations (6-31G level) on the triquinolina triscationic
      bicyclophane. This compound exists as two diastereomeric sets of enantiomers, one
      with C3 symmetry and the other with C1 symmetry. The C3-symmetrical derivative is
      1.94 kcal mol(-1) more stable than its C1-symmetrical one. This energy difference
      is sufficient to consider the former and its enantiomer the only two
      conformations existing in solution at room temperature.

PMID- 15989367
TI  - Highly efficient, reversible addition of activated methylene compounds to styrene
      derivatives catalyzed by silver catalysts.
AB  - [reaction: see text] A highly efficient inter- and intramolecular addition of 1,3
      diketone/beta-ketoester to alkenes was developed by using silver catalysts.
      Silver triflate shows the highest catalytic activity. The reaction is reversible
      through the cleavage of a carbon-carbon bond by silver at an elevated
      temperature.

PMID- 15989368
TI  - Formal synthesis of (-)-perhydrohistrionicotoxin via cyclic amino acid ester
      enolate Claisen rearrangement and ring-closing metathesis.
AB  - [reaction: see text] We have successfully synthesized an advanced synthetic
      intermediate, hydroxy lactam 3, which has previously been converted to
      perhydrohistrionicotoxin. An important feature of this synthesis is the creation
      of stereogenic centers by using the cyclic amino acid ester-enolate Claisen
      rearrangement together with a ring-closing metathesis for azaspirocyclic skeleton
      construction.

PMID- 15989369
TI  - Reactions of enamines with selectfluor: a straightforward route to difluorinated
      carbonyl compounds.
AB  - [reaction: see text] Reactions of enamines, preformed from beta-dicarbonyl and
      monocarbonyl compounds, with Selectfluor (1-chloromethyl-4-fluoro-1,4
      diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) under mild conditions
      (triethylamine (TEA) or molecular sieves) easily led to the corresponding
      difluorinated carbonyl compounds in high yields.

PMID- 15989370
TI  - A new route to methyl (R,E)-(-)-tetradeca-2,4,5-trienoate (pheromone of
      Acanthoscelides obtectus) utilizing a palladium-catalyzed asymmetric allene
      formation reaction.
AB  - [reaction: see text] A formal total synthesis of the sex attractant of male dried
      bean beetle, methyl (R,E)-(-)-tetradeca-2,4,5-trienoate, was achieved by a new
      efficient route utilizing the Pd-catalyzed asymmetric allene synthesis reaction.
      It was found that the atropisomeric biaryl bisphosphine (R)-segphos showed better
      enantioselectivity than (R)-binap in the Pd-catalyzed reaction for preparing
      alkyl-substituted axially chiral allenes.

PMID- 15989371
TI  - A facile oxidation and oxygen insertion of the cyclopentadiene ring by molecular
      oxygen in solution.
AB  - [reaction: see text] Oxidation of substituted cyclopentadienes by molecular
      oxygen afforded the corresponding pyrylium cations in acidic solution, whereby an
      oxygen atom was inserted into the cyclopentadiene ring. This novel one-step
      reaction proceeds in a different yield depending on substitution patterns of the
      cyclopentadiene. A possible reaction pathway and formation mechanism of the
      pyrylium cation are proposed and discussed.

PMID- 15989373
TI  - JOC recent reviews. Number 77.

PMID- 15989374
TI  - Manifestations and management of chronic insomnia in adults.

PMID- 15989375
TI  - Update on acute bacterial rhinosinusitis.

PMID- 15989376
TI  - Post-myocardial infarction depression.

PMID- 15989377
TI  - Knowledge and access to information on recruitment of underrepresented
      populations to cancer clinical trials.

PMID- 15989378
TI  - Plantar fasciitis: diagnosis and therapeutic considerations.
AB  - Plantar fasciitis is the most common cause of inferior heel pain. The pain and
      discomfort associated with this condition can have a dramatic impact on physical
      mobility. The etiology of this condition is not clearly understood and is
      probably multi-factorial in nature. Weight gain, occupation-related activity,
      anatomical variations, poor biomechanics, overexertion, and inadequate footwear
      are contributing factors. Although plantar fasciitis is generally regarded as a
      self-limited condition, it can take months to years to resolve, presenting a
      challenge for clinicians. Many treatment options are available that demonstrate
      variable levels of efficacy. Conservative therapies include rest and avoidance of
      potentially aggravating activities, stretching and strengthening exercises,
      orthotics, arch supports, and night splinting. Other considerations include use
      of anti-inflammatory agents, ultrasonic shockwave therapy, and, in the most
      extreme cases, surgery. This article reviews plantar fasciitis, presents the most
      effective treatment options currently available, and proposes nutritional
      considerations that may be beneficial in the management of this condition.

PMID- 15989379
TI  - Benefits and requirements of vitamin D for optimal health: a review.
AB  - Vitamin D sufficiency is required for optimal health. The conditions with strong
      evidence for a protective effect of vitamin D include several bone diseases,
      muscle weakness, more than a dozen types of internal cancers, multiple sclerosis,
      and type 1 diabetes mellitus. There is also weaker evidence for several other
      diseases and conditions. There are good reasons that vitamin D sufficiency be
      maintained during all stages of life, from fetal development to old age. Adequate
      calcium intake is also recommended. The current vitamin D requirements in the
      United States are based on protection against bone diseases. These guidelines are
      being revised upward in light of new findings, especially for soft-tissue health.
      The consensus of scientific understanding appears to be that vitamin D deficiency
      is reached for serum 25-hydroxyvitamin D (25OHD) levels less than 20 ng/mL (50
      nmol/L), insufficiency in the range from 20-32 ng/mL, and sufficiency in the
      range from 33-80 ng/mL, with normal in sunny countries 54-90 ng/mL, and excess
      greater than 100 ng/mL. Solar ultraviolet-B (UVB) irradiation is the primary
      source of vitamin D for most people. In general, the health benefits accruing
      from moderate UV irradiation, without erythema or excess tanning, greatly
      outweigh the health risks, with skin pigmentation (melanin) providing much of the
      protection. In the absence of adequate solar UVB irradiation due to season,
      latitude, or lifestyle, vitamin D can be obtained from fortified food, oily fish,
      vitamin D supplements, and artificial sources of UVB radiation.

PMID- 15989380
TI  - An exploratory ethnobotanical study of the practice of herbal medicine by the
      Akan peoples of Ghana.
AB  - This exploratory ethnobotanical study took place in Kumasi, the capital city of
      the Asante, one of the Akan tribes. Data was collected using the multi-method
      approach of descriptive review, semi-structured interviews with traditional
      medical practitioners, and brief scientific review. Traditional Akan medicine is
      holistic and does not separate the physical world from the supernatural world. It
      is deeply rooted in traditional religion, with illness seen as a departure from
      the natural equilibrium. Traditional healers are either spiritually based or non
      spiritually based. This study found the traditional knowledge of healing and use
      of medicinal plants is disseminated through generations by family members.
      However, the acquisition of academic qualifications is now a priority, and formal
      training is taking place in the workplace and a university. Techniques used in
      diagnosis and treatment consist of a fusion of traditional and biomedical
      methods. Treatment of hypertension was used as an example, with all practitioners
      recognizing hypertension's clinical signs and symptoms. Medicinal plants are
      predominantly wildcrafted and dispensed mainly by decoction, although prepared
      formulas are given. To prevent self-medication, patients are seen frequently.
      Scientific evidence validates the pharmacological actions of the medicinal
      plants. Public health care in Ghana is accessed by a cash and carry system that
      is only available to those who can afford it. Approximately 75 percent of the
      population depends on traditional medicine for primary health care. A national
      health insurance scheme was introduced in 2004, and it has been proposed that
      traditional medicine will be integrated into this new system.

PMID- 15989381
TI  - Safety and effectiveness of an L-lysine, zinc, and herbal-based product on the
      treatment of facial and circumoral herpes.
AB  - CONTEXT: L-lysine, an essential amino acid, inhibits normal replication of Herpes
      simplex virus (HSV), shortening the normal course and duration of the disease.
      This study was conducted to determine the effectiveness of a combination of L
      lysine with botanicals and other nutrients in relieving the symptoms of facial
      and circumoral herpes. METHODS: This small pilot study was conducted using an
      outcome (open-label) model. Thirty male and female participants (15 in each
      group) meeting the inclusion/exclusion criteria were admitted to the study. The
      10 outcome measures used to monitor the sores were tingling, itching, burning,
      tenderness, prickling, soreness, bump/swelling, small blister(s), oozing
      blister(s), and crusting, as well as before-and-after photographs of the lesion,
      and a daily diary. RESULTS: At the end of treatment the ointment produced full
      resolution in 40 percent of the participants by the third day and in 87 percent
      by the end of the sixth day. A cold sore episode may last up to 21 days without
      treatment. CONCLUSIONS: Overall data indicated significant improvement in
      participants by the sixth day of treatment for all but two participants. There
      were no adverse effects reported during this study.

PMID- 15989382
TI  - Lutein and zeaxanthin. Monograph.

PMID- 15989383
TI  - L-theanine . Monograph.

PMID- 15989384
TI  - L-arginine. Monograph.

PMID- 15989385
TI  - When conversation is not enough: assessing infinitival complements through
      elicitation.
AB  - Children with language impairment have been found to show limited usage of
      infinitival complements, one of the earliest complex sentence types to emerge and
      a significant form in school-age language. Children's production of infinitival
      complements in conversation is not sufficient to tell us what they know about
      this form. This article describes a story completion procedure for eliciting
      infinitival complements. The procedure includes 2 situational contexts requiring
      different infinitive sentence forms and a variety of verbs with which infinitival
      complements can be produced. The child's response includes both production of an
      utterance to complete each story and then an acting out of the meaning of that
      utterance. This enables the examiner to look not only at the forms produced by
      the child but also at the relationship between form and meaning.

PMID- 15989386
TI  - Working memory in aphasia: theory, measures, and clinical implications.
AB  - Recently, researchers have suggested that deficits in working memory capacity
      contribute to language-processing difficulties observed in individuals with
      aphasia (e.g., I. Caspari, S. Parkinson, L. LaPointe, & R. Katz, 1998; R. A.
      Downey et al., 2004; N. Friedmann & A. Gvion, 2003; H. H. Wright, M. Newhoff, R.
      Downey, & S. Austermann, 2003). A theoretical framework of working memory can aid
      in our understanding of a disrupted system (e.g., after stroke) and how this
      relates to language comprehension and production. Additionally, understanding the
      theoretical basis of working memory is important for the measurement and
      treatment of working memory. The literature indicates that future investigations
      of measurement and treatment of working memory are warranted in order to
      determine the role of working memory in language processing.

PMID- 15989387
TI  - Oral language expectations for African American children in grades 1 through 5.
AB  - Reference profiles for characterizing the language abilities of elementary-grade
      African American students are important for assessment and instructional
      planning. H. K. Craig and J. A. Washington (2002) reported performance for 100
      typically developing preschoolers and kindergartners on 5 traditional language
      measures: mean length of communication units, amount of complex syntax
      production, number of different spoken words, responses to wh-questions, and
      understanding of active/passive sentence construction. The present study reports
      performances on the same measures for 295 typically developing African American
      children in the 1st through 5th grades. Findings revealed increasing performance
      scores with increasing grades on 4 of the tasks. A ceiling effect was evident on
      the task that assessed comprehension of active and passive voice. Gender,
      socioeconomic status, and community influenced the values in systematic ways, and
      responses to requests for information varied relative to vocabulary skill. These
      measures are recommended for inclusion in culturally fair assessment protocols
      designed to characterize the language abilities of elementary-grade African
      American students.

PMID- 15989388
TI  - Use of narrative-based language intervention with children who have specific
      language impairment.
AB  - Ten 7-8-year-old children with specific language impairment participated in a 6
      week program of narrative-based language intervention (NBLI) in an effort to
      evaluate NBLI's feasibility. Each intervention session targeted story content as
      well as story and sentence form using story retell and generation tasks. Eight
      children achieved the clinically significant improvement criterion from pre- and
      posttest comparisons of at least 1.45 points on a narrative quality (NQ) rating
      (p<.013). Throughout the NBLI program, the children were informally observed to
      show increased self-confidence in their narrative production skills. Nearly all
      children preferred story generation activities over story retell tasks, while
      story retell tasks were favored over sentence imitation drills. Pre- and posttest
      comparisons for number of different words, developmental sentence score, and a
      sentence imitation task were nonsignificant. This indicated no further evidence
      of positive outcomes for NBLI. Based on the significant findings for NQ, NBLI is
      worthy of further investigation. Modifications to enhance its ability to produce
      positive gains are discussed.

PMID- 15989389
TI  - Effect of presentation modality on immediate and delayed recall in individuals
      with Alzheimer's disease.
AB  - Episodic memory (EM) deficits are the hallmark of Alzheimer's disease (AD). Story
      retelling tasks are particularly sensitive to EM impairments and require
      participants to recall a short story immediately and after a delay. The purpose
      of this study was to determine whether presentation modality influences story
      recall in AD participants. Thirty AD participants and 30 healthy elders recalled
      short stories in (a) auditory, (b) visual, and (c) combined auditory-visual
      modalities. Recall was assessed immediately as well as after 15- and 30-min
      delays. Presentation modality significantly influenced story recall in AD
      participants. AD participants demonstrated better recall after silently reading a
      story than after hearing an examiner tell the story or simultaneously hearing and
      reading the story. Clinical implications of these results are discussed.

PMID- 15989390
TI  - Concurrent validity of the language development survey: associations with the
      MacArthur-Bates communicative development inventories: words and sentences.
AB  - This study examined the concurrent validity of the Language Development Survey
      (LDS), a 310-word parent report screening tool for language delay in toddlers, by
      testing its associations with the MacArthur-Bates Communicative Development
      Inventories: Words and Sentences (CDI:WS), a 680-word parent report instrument.
      Participants were 239 toddlers 23-25 months of age. The correlation between total
      vocabulary score on the 2 instruments was .95, and correlations across comparable
      semantic categories ranged from .84 to .94. The correlation between the LDS and
      the CDI:WS for mean length of phrases calculated on 3 examples of the child's
      longest and best phrases was .90. Both instruments demonstrated that parents
      reported higher vocabulary and mean phrase length scores for girls. The study
      indicates that information obtained from the LDS about rank ordering of toddlers
      in terms of their reported vocabulary and mean length of phrases is equivalent to
      that obtained from the longer CDI:WS.

PMID- 15989391
TI  - Effect of rate reduction and increased loudness on acoustic measures of
      anticipatory coarticulation in multiple sclerosis and Parkinson's disease.
AB  - The present study compared patterns of anticipatory coarticulation for utterances
      produced in habitual, loud, and slow conditions by 17 individuals with multiple
      sclerosis (MS), 12 individuals with Parkinson's disease (PD), and 15 healthy
      controls. Coarticulation was inferred from vowel F2 frequencies and consonant
      first-moment coefficients. Rate-related changes in coarticulation differed
      depending on the particular phonetic events in an utterance. In some instances,
      the slow condition was associated with stronger anticipatory effects, but in
      other instances the slow condition was associated with weaker anticipatory
      effects, relative to other speaking conditions. In contrast, coarticulatory
      patterns for the loud and habitual conditions typically did not differ.
      Coarticulatory patterns also tended to be similar among speaker groups within
      each condition. Finally, when acoustic measures of coarticulation differed among
      speaking conditions, the direction and magnitude of the effect generally were
      similar for healthy controls, speakers with MS, and speakers with PD. These
      results are consistent with studies suggesting mostly preserved patterns of
      coarticulation for speakers with mild to moderate dysarthria, as well as research
      indicating only subtle coordination deficits for individuals with dysarthria. The
      finding that increased loudness had a negligible effect on coarticulation also
      appears to be at odds with the suggestion that increased loudness stimulates
      orofacial coordination for speakers with dysarthria, although studies including
      speakers exhibiting coordination impairments at habitual speaking rates would
      provide a stronger test of this suggestion. Lastly, the fact that speaking
      condition similarly affected acoustic measures of anticipatory coarticulation for
      all speaker groups suggests the feasibility of applying theories and models of
      speech production for neurologically normal talkers to the study of dysarthria.

PMID- 15989392
TI  - Lexical priming in picture naming of young children who do and do not stutter.
AB  - The purpose of this investigation was to assess the influence of lexical/semantic
      priming on the speech reaction time of young children who do and do not stutter
      during a picture-naming task. Participants were 23 children who stutter, age
      matched (+/-4 months) to 23 children who do not stutter, ranging in age from 3;0
      (years;months) to 5;11. Procedures involved a computer-assisted picture-naming
      task, during which each participant was presented with the same set of 28
      pictures in each of 3 different conditions: (a) no-prime condition, in which no
      auditory stimulus was presented before picture display; (b) related-prime
      condition, in which a word, semantically related to the target picture, was
      presented auditorily 700 ms before picture display; and (c) unrelated-prime
      condition, in which a semantically unrelated word was presented auditorily 700 ms
      before picture display. Results indicated that when compared with a no-prime
      condition, presentation of semantically related words before the picture-naming
      response led to shorter or faster speech reaction times for children who do not
      stutter, but for children who stutter, it led to longer or slower speech reaction
      times. Moreover, children who do not stutter and who had higher receptive
      vocabulary scores exhibited faster speech reaction times and a greater semantic
      priming effect, whereas no such relationships were found for children who
      stutter. Findings were taken to suggest that children who stutter may exhibit
      subtle difficulties with lexical encoding and that this difficulty with speech
      language planning may be one variable that contributes to childhood stuttering.

PMID- 15989393
TI  - Speech interactions with linguistic, cognitive, and visuomotor tasks.
AB  - Lip movements were examined across several repetitive speaking conditions (speech
      alone and speaking concurrently with a linguistic, cognitive, or visuomotor
      challenge task) in 20 young adults. Performance in these nonspeech activities was
      also compared between isolated tasks and concurrent speech conditions. Linguistic
      challenges resulted in increased spatiotemporal variability of lip displacement
      across repetitions. Motor challenges led to more rapid speech with smaller lip
      displacement. These qualitatively different changes suggest that different
      aspects of attention are required for linguistic versus manual visuomotor
      activity. Vocal intensity increased for all concurrent task conditions compared
      with speech alone, suggesting increased effort compared to the control condition.
      Scores for linguistic performance decreased when utterance repetition occurred
      concurrently with the syntactic challenge. These findings reveal that speech
      motor activity can influence linguistic performance as well as be influenced by
      it. Although these data come from healthy speakers, they suggest that clinicians
      working with disordered speakers should not overlook the potential interactions
      among the demands of language formulation, cognitive activity, and speech motor
      performance.

PMID- 15989394
TI  - Forced-choice analysis of segmental production by Chinese-accented English
      speakers.
AB  - This study describes the development of a minimal-pairs word list targeting
      phoneme contrasts that pose difficulty for Mandarin Chinese-speaking learners of
      English as a second language. The target phoneme inventory was compiled from
      analysis of phonetic transcriptions of about 800 mono- and polysyllabic English
      words with examples of all the vowels, diphthongs, and syllable onsets and codas
      of the language. The Mandarin-specific minimal-pairs list derived from the
      phonetic transcription analyses contains 190 items. Tape recordings were made of
      8 Mandarin speakers reading a randomized version of target items from the minimal
      pairs list and a set of 20 sentences. Listeners who were native American English
      speakers judged the words in a forced-choice task and wrote down what they
      understood of the sentences. Correlations between listener responses on the
      forced-choice task and the sentence intelligibility scores showed differences in
      the strength of the relationship with sentence intelligibility across categories
      of minimal-pairs contrasts. Multiple regression analysis found listener responses
      on the minimal-pairs task to account for approximately 76% of the variance in
      speakers' sentence intelligibility scores, showing that performance on the
      minimal pairs of the probe list does predict connected speech intelligibility.
      Analyses of individual contrasts indicate target phonemes most often misperceived
      by native listeners.

PMID- 15989395
TI  - Application of psychometric theory to the measurement of voice quality using
      rating scales.
AB  - Rating scales are commonly used to study voice quality. However, recent research
      has demonstrated that perceptual measures of voice quality obtained using rating
      scales suffer from poor interjudge agreement and reliability, especially in the
      mid-range of the scale. These findings, along with those obtained using
      multidimensional scaling (MDS), have been interpreted to show that listeners
      perceive voice quality in an idiosyncratic manner. Based on psychometric theory,
      the present research explored an alternative explanation for the poor
      interlistener agreement observed in previous research. This approach suggests
      that poor agreement between listeners may result, in part, from measurement
      errors related to a variety of factors rather than true differences in the
      perception of voice quality. In this study, 10 listeners rated breathiness for 27
      vowel stimuli using a 5-point rating scale. Each stimulus was presented to the
      listeners 10 times in random order. Interlistener agreement and reliability were
      calculated from these ratings. Agreement and reliability were observed to improve
      when multiple ratings of each stimulus from each listener were averaged and when
      standardized scores were used instead of absolute ratings. The probability of
      exact agreement was found to be approximately .9 when using averaged ratings and
      standardized scores. In contrast, the probability of exact agreement was only .4
      when a single rating from each listener was used to measure agreement. These
      findings support the hypothesis that poor agreement reported in past research
      partly arises from errors in measurement rather than individual differences in
      the perception of voice quality.

PMID- 15989396
TI  - Comparison of measures of variability of speech movement trajectories using
      synthetic records.
AB  - In speech research, it is often desirable to assess quantitatively the
      variability of a set of speech movement trajectories. This problem is studied
      here using synthetic trajectories, which consist of a common pattern and terms
      representing amplitude and phase variability. The results show that a technique
      for temporal alignment of the records based on functional data analysis allows us
      to extract the pattern and variability terms as separate functions, with good
      approximation. Indices of amplitude and phase variability are defined, which
      provide a more accurate assessment of variability than previous approaches.

PMID- 15989397
TI  - The role of home literacy practices in preschool children's language and emergent
      literacy skills.
AB  - This study examined how 4 specific measures of home literacy practices (i.e.,
      shared book reading frequency, maternal book reading strategies, child's
      enjoyment of reading, and maternal sensitivity) and a global measure of the
      quality and responsiveness of the home environment during the preschool years
      predicted children's language and emergent literacy skills between the ages of 3
      and 5 years. Study participants were 72 African American children and their
      mothers or primary guardians primarily from low-income families whose home
      literacy environment and development have been followed since infancy. Annually,
      between 18 months and 5 years of age, the children's mothers were interviewed
      about the frequency they read to their child and how much their child enjoyed
      being read to, and the overall quality and responsiveness of the home environment
      were observed. Mothers also were observed reading to their child once a year at
      2, 3, and 4 years of age, and maternal sensitivity and types of maternal book
      reading strategies were coded. Children's receptive and expressive language and
      vocabulary were assessed annually between 3 years of age and kindergarten entry,
      and emergent literacy skills were assessed at 4 years and kindergarten entry. The
      specific home literacy practices showed moderate to large correlations with each
      other, and only a few significant associations with the language and literacy
      outcomes, after controlling for maternal education, maternal reading skills, and
      the child's gender. The global measure of overall responsiveness and support of
      the home environment was the strongest predictor of children's language and early
      literacy skills and contributed over and above the specific literacy practice
      measures in predicting children's early language and literacy development.

PMID- 15989398
TI  - Probed serial recall in Williams syndrome: lexical influences on phonological
      short-term memory.
AB  - Williams syndrome is a genetic disorder that, it has been claimed, results in an
      unusual pattern of linguistic strengths and weaknesses. The current study
      investigated the hypothesis that there is a reduced influence of lexical
      knowledge on phonological short-term memory in Williams syndrome. Fourteen
      children with Williams syndrome and 2 vocabulary-matched control groups, 20
      typically developing children and 13 children with learning difficulties, were
      tested on 2 probed serial-recall tasks. On the basis of previous findings, it was
      predicted that children with Williams syndrome would demonstrate (a) a reduced
      effect of lexicality on the recall of list items, (b) relatively poorer recall of
      list items compared with recall of serial order, and (c) a reduced tendency to
      produce lexicalization errors in the recall of nonwords. In fact, none of these
      predictions were supported. Alternative explanations for previous findings and
      implications for accounts of language development in Williams syndrome are
      discussed.

PMID- 15989399
TI  - Preschoolers learning Hmong and English: lexical-semantic skills in L1 and L2.
AB  - Picture naming and picture identification tasks were used to investigate lexical
      semantic skills in young children learning Hmong as a first language (L1) and
      English as a second language (L2). A total of 19 children, ages 3;4
      (years;months)-5;2, participated in this study. Performance on lexical tasks was
      analyzed as a function of development (older and younger participants), language
      (Hmong and English), modality (receptive and expressive skills), and the nature
      of total or "composite" vocabulary scores (translation equivalents or singles,
      reflecting comparable forms in both languages as compared to concepts lexicalized
      into only 1 language). Older participants outperformed younger participants in
      English, but not Hmong, indicating a relative stabilization of L1 skills,
      alongside more robust growth in L2. The difference between expressive and
      receptive performance was also much greater in Hmong than English. Composite
      scores were always greater than single language scores and the proportion of
      translation equivalents increased with age.

PMID- 15989400
TI  - The incidence of error in young children's Wh-questions.
AB  - Many current generativist theorists suggest that young children possess the
      grammatical principles of inversion required for question formation but make
      errors because they find it difficult to learn language-specific rules about how
      inversion applies. The present study analyzed longitudinal spontaneous sampled
      data from twelve 2-3-year-old English speaking children and the intensive diary
      data of 1 child (age 2;7 [years;months] to 2;11) in order to test some of these
      theories. The results indicated significantly different rates of error use across
      different auxiliaries. In particular, error rates differed across 2 forms of the
      same auxiliary subtype (e.g., auxiliary is vs. are), and auxiliary DO and modal
      auxiliaries attracted significantly higher rates of errors of inversion than
      other auxiliaries. The authors concluded that current generativist theories might
      have problems explaining the patterning of errors seen in children's questions,
      which might be more consistent with a constructivist account of development.
      However, constructivists need to devise more precise predictions in order to
      fully explain the acquisition of questions.

PMID- 15989401
TI  - A functional magnetic resonance imaging investigation of verbal working memory in
      adolescents with specific language impairment.
AB  - This study used neuroimaging and behavioral techniques to examine the claim that
      processing capacity limitations underlie specific language impairment (SLI).
      Functional magnetic resonance imaging (fMRI) was used to investigate verbal
      working memory in adolescents with SLI and normal language (NL) controls. The
      experimental task involved a modified listening span measure that included
      sentence encoding and recognition of final words in prior sets of sentences. The
      SLI group performed significantly poorer than the NL group for both encoding and
      recognition and displayed slower reaction times for correct responses on high
      complexity encoding items. fMRI results revealed that the SLI group exhibited
      significant hypoactivation during encoding in regions that have been implicated
      in attentional and memory processes, as well as hypoactivation during recognition
      in regions associated with language processing. Correlational analyses indicated
      that adolescents with SLI exhibited different patterns of coordinating activation
      among brain regions relative to controls for both encoding and recognition,
      suggesting reliance on a less functional network. These findings are interpreted
      as supporting the notion that constraints in nonlinguistic systems play a role in
      SLI.

PMID- 15989402
TI  - Differences at 17 months: productive language patterns in infants at familial
      risk for dyslexia and typically developing infants.
AB  - Productive vocabulary composition is investigated in 17-month-old children who
      are participating in an ongoing longitudinal dyslexia research project in the
      Netherlands. The project is searching for early precursors for dyslexia and
      follows a group of children who are genetically at risk for dyslexia and a
      control group during the first 10 years of their lives. Among other measures, the
      Dutch version of the MacArthur Communicative Development Inventory: Words and
      Sentences (N-CDI) is used to investigate early vocabulary development. In this
      article, the first N-CDI results from the 2 groups of 17-month-old children are
      compared with each other, with other cross-sectional, cross-linguistic studies,
      and with a similar Finnish longitudinal dyslexia project. The Dutch children show
      the same general acquisition pattern as documented for other languages, but there
      are significant differences between the two groups of 17-month-old children in
      total number of words produced and in the linguistic composition of their
      productive vocabulary.

PMID- 15989403
TI  - Word learning in children with vocabulary deficits.
AB  - Word learning in 16 children with specific language impairment (SLI) was compared
      with that of chronological-age controls (CAC) and vocabulary-age controls (VAC),
      to examine the extent and nature of word-learning deficits in the children with
      SLI. The children were exposed to novel words in a story and an explicit teaching
      context. Five tasks assessed how much the children had learned about the words'
      phonological form and semantic properties after 6 repetitions (Time 1) and again
      after 12 repetitions (Time 2) of the words in each context. The SLI group
      performed significantly worse than the CAC group at both Time 1 and Time 2 on all
      measures of the words presented in both contexts. They performed similarly to the
      VAC group (who were on average 21/2 years younger) on Time 1 and Time 2 measures
      from both contexts, except for the Naming task at Time 2, on which their
      performance was significantly lower. These findings suggest that children with
      vocabulary deficits have difficulties with both phonological and semantic aspects
      of word learning.

PMID- 15989404
TI  - Age 13 language and reading outcomes in late-talking toddlers.
AB  - Language and reading outcomes at 13 years of age were examined in 28 children
      identified at 24 to 31 months as late talkers, all of whom came from middle- to
      upper-class socioeconomic status (SES) families and had normal nonverbal ability
      and age-adequate receptive language at intake. Late talkers were compared with a
      group of 25 typically developing children matched at intake on age, SES, and
      nonverbal ability. As a group, late talkers performed in the average range on all
      standardized language and reading tasks at age 13. However, they scored
      significantly lower than SES-matched peers on aggregate measures of vocabulary,
      grammar, and verbal memory, as well as on reading comprehension. They were
      similar to comparison peers in reading mechanics and writing aggregates.
      Intercorrelations between outcome measures were moderately high, suggesting
      considerable shared variance. Regression analyses indicated that age 2 Language
      Development Survey vocabulary score was a significant predictor of age 13
      vocabulary, grammar, verbal memory, and reading comprehension. Findings suggest
      that slow language development at age 2-2 1/2 is associated with a weakness in
      language-related skills into adolescence relative to typically developing peers.

PMID- 15989405
TI  - The association between cardiovascular disease and cochlear function in older
      adults.
AB  - The purpose of this research was to evaluate the relation between self-reported
      cardiovascular disease (CVD) and cochlear function in older adults. The
      Epidemiology of Hearing Loss Study (EHLS) is an ongoing population-based study of
      hearing loss and its risk factors in Beaver Dam, Wisconsin. As part of the EHLS
      questionnaire, participants were asked about their cardiovascular medical
      history. CVD history was determined from questions regarding history of angina,
      myocardial infarction (MI), and stroke. Questions about the use of
      antihypertensive medication and blood pressure measurements determined the
      presence or absence of hypertension. Among the audiologic measures completed were
      distortion product otoacoustic emissions (DPOAEs). Cochlear function was measured
      using DPOAEs and participants were categorized as having (a) cochlear impairment,
      (b) possible cochlear impairment, or (c) no cochlear impairment. There were 1,501
      participants with complete CVD and DPOAE data from the 1998-2000 examination
      phase. Women with a self-reported history of MI were twice as likely (age
      adjusted odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.15-3.46) to
      have cochlear impairment than women without a history of MI. This association was
      not significant in men (age-adjusted OR = 0.98, 95% CI = 0.61-1.58).
      Additionally, no other CVD variables were associated with cochlear impairment.
      This study provides data on a possible sex-specific association between CVD and
      DPOAEs in older adults.

PMID- 15989406
TI  - Effects of age and hearing loss on gap detection and the precedence effect:
      narrow-band stimuli.
AB  - Deficits in temporal resolution and/or the precedence effect may underlie part of
      the speech understanding difficulties experienced by older listeners in degraded
      acoustic environments. In a previous investigation, R. Roberts and J. Lister
      (2004) identified a positive correlation between measures of temporal resolution
      and the precedence effect, specifically across-channel gap detection (as measured
      dichotically) and fusion. Across-channel gap detection may also be measured using
      frequency-disparate markers. Thus, the present investigation was designed to
      determine if the relation is specific to dichotic gap detection or may generalize
      to all types of across-channel gap detection. Gap-detection thresholds (GDTs) for
      fixed-frequency and frequency-disparate markers and lag-burst thresholds (LBTs)
      were measured for 3 groups of listeners: young with normal hearing sensitivity
      (YNH), older with normal hearing sensitivity (ONH), and older with sensorineural
      hearing loss (OIH). Also included were conditions of diotic and dichotic GDT.
      Largest GDTs were measured for the frequency-disparate markers, whereas largest
      LBTs were measured for the fixed-frequency markers. ONH and OIH listeners
      exhibited larger frequency-disparate and dichotic GDTs than YNH listeners.
      Listener age and hearing loss appeared to influence temporal resolution for
      frequency-disparate and dichotic stimuli, which is potentially important for the
      resolution of timing cues in speech. Age and hearing loss did not significantly
      influence fusion as measured by LBTs. Within each participant group, most GDTs
      and LBTs were positively, but not significantly, correlated. For all participants
      combined, across-channel GDTs and LBTs were positively and significantly
      correlated. This suggests that the 2 tasks may rely on a common across-channel
      temporal mechanism.

PMID- 15989407
TI  - Auditory brainstem responses in young males with Fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common inherited cause of mental retardation
      resulting in developmental delays in males. Atypical outer ear morphology is
      characteristic of FXS and may serve as a marker for abnormal auditory function.
      Despite this abnormality, studies of the hearing of young males with FXS are
      generally lacking. A few studies have suggested that a significant proportion of
      individuals with FXS demonstrate prolonged auditory brainstem response (ABR)
      latencies. The purpose of this study was to determine whether young males with
      FXS display atypical auditory brainstem function compared to typically developing
      males when conductive and sensorineural hearing loss are ruled out as possible
      contributors to atypical findings. Participants were 23 males with FXS, 21
      typically developing males who were matched for developmental age, and 17
      typically developing males who were matched for chronological age. A battery of
      tests to assess peripheral hearing, cochlear function, and auditory pathway
      integrity through the level of the brainstem was completed. Males with FXS were
      similar to typically developing males who were matched for developmental age
      level or chronological age level on all measures. They had normal hearing
      sensitivity and middle ear function and scored similar to the typically
      developing children on the measures of auditory brainstem pathway integrity. In
      summary, ABRs in young males with FXS were within normal limits.

PMID- 15989409
TI  - Report from the CDC. Changes in selected chronic disease-related risks and health
      conditions for nonpregnant women 18-44 years old BRFSS.
AB  - We examined changes in the prevalence of selected chronic disease-related
      indicators among women aged 18-44 years using the Behavioral Risk Factor
      Surveillance System (BRFSS) data for two time periods, 1991-1992 and 2000-2001.
      We examined alcohol use, cigarette smoking, leisure time physical activity, body
      mass index (BMI), having had Pap smear screening, and having been diagnosed with
      hypertension, diabetes, high cholesterol, and asthma. We created a multicondition
      index by combining multiple chronic disease-related conditions. Younger women,
      <25 years of age, reported a higher prevalence of cigarette smoking and binge
      drinking. Black women and women with lower educational levels had a higher
      prevalence of obesity, and higher proportions were diagnosed with hypertension
      and diabetes. About 35% of the women had been diagnosed with at least one chronic
      disease-related condition. More than 10% of black women reported being diagnosed
      with two chronic disease-related conditions, compared with 7% in white women and
      8% in Hispanic women. The BRFSS data can be used for monitoring the prevalence of
      multiple chronic disease-related behaviors and conditions.

PMID- 15989410
TI  - Toward optimal health: Linda Brubaker, M.D. discusses urinary incontinence
      [Interview by Jodi R Godfrey].

PMID- 15989411
TI  - Supplementation with DHEA: effect on muscle size, strength, quality of life, and
      lipids.
AB  - OBJECTIVE: To evaluate the effects of combination estrogen/androgen therapy on
      muscle mass, strength and endurance, serum hormone and lipid profiles, and
      quality of life measures in postmenopausal women. METHODS: Prospective,
      randomized, placebo-controlled pilot study at a tertiary care medical center.
      Fifty postmenopausal women were randomized to a 12-week course of (1)
      dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen
      (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main
      outcome measures of lower extremity muscle (calf) mass, functional muscle
      parameters, serum hormone and lipid levels, and quality of life (QOL) were
      obtained at baseline and after treatment. Statistical analysis compared percent
      change from baseline values and treatment differences among outcomes. RESULTS:
      Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and
      androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments
      when compared with placebo. Compared with no hormone therapy, none of the
      supplemental hormone groups caused significant changes in muscle mass, muscle
      strength, muscle endurance, feelings of well-being, sleep, or sexual function.
      CONCLUSIONS: Androgen replacement therapy, with DHEA, to menopausal women
      increases serum androgen levels without any appreciable effect on muscle cross
      sectional area, muscle strength, muscle function, or improvement in health
      related QOL.

PMID- 15989412
TI  - Correlates of prescription drug use during pregnancy.
AB  - PURPOSE: To evaluate the extent of prescription drug use and the use of category
      D or X drugs during pregnancy and examine the maternal characteristics associated
      with use. METHODS: Medical record and survey data from an observational cohort of
      pregnant women from 2001 to 2003 (n=1626) were analyzed to examine the use of
      prescription drugs and the use of category D or X drugs. RESULTS: A majority of
      these pregnant women were prescribed a prescription drug (56%), and 4% of women
      were prescribed a category D or X drug. The most common classes of medications
      prescribed were antibiotics (62%), analgesics (18%), asthma medications (18%),
      and antiemetics (17%). After adjustment for sociodemographic and clinical
      characteristics, African American women were more likely to use a prescription
      drug than white women. Lower levels of educational attainment were also
      associated with greater use of prescription drugs compared with women who had
      graduated from college. Women with a chronic health condition, gestational
      diabetes, a prenatal hospitalization, a history of infertility, or symptoms of
      acid reflux were also more likely to use a prescription drug than women without
      these conditions. Nulliparous women and women who were married or living with a
      partner were less likely to use category D or X drugs during pregnancy than women
      without these characteristics. Women with a history of infertility and those with
      a chronic health condition were more likely to use a category D or X drugs during
      pregnancy than those without these conditions. CONCLUSIONS: The common use of
      prescription drugs during pregnancy supports the importance of expanding the
      evidence about the risks and benefits of prescription drug use during pregnancy
      and suggests the need for systems to safeguard prescribing practices for women of
      reproductive age.

PMID- 15989413
TI  - Effects of hormone replacement on progression of coronary calcium as measured by
      electron beam tomography.
AB  - PURPOSE: The recent Women's Health Initiative (WHI) results have demonstrated
      that combined estrogen plus progestin imparts a small but significant increase in
      cardiovascular risk and breast cancer among asymptomatic women. However, the
      effect and potential benefit of unopposed estrogen is not as clear. We sought to
      evaluate the progression of subclinical atherosclerosis in postmenopausal women
      using no hormone replacement therapy (HRT), combined therapy, and estrogen alone
      in an observational study. METHODS: Postmenopausal women without symptoms or
      known coronary heart disease (CHD) were evaluated at our center for follow-up of
      coronary calcification. Patients were physician referred and underwent two
      consecutive electron beam tomography scans at least 1 year apart. All women
      fitting the study criteria were asked to participate, and those who consented
      were included. Demographic data, risk factors for CHD, HRT, and other medication
      use were collected by interview. RESULTS: The study included 177 asymptomatic
      women. Calcium progression was 14.6%+/-21% in women taking any hormone therapy
      (n=97). Annual calcium progression rates in nonusers (n=80) was 22.3%+/-32%.
      Relative to the nonuser group, HRT treatment inhibited the progression of
      atherosclerosis by 35% (p=0.01). This effect was independent of age, risk,
      cardiovascular factors, statin use, or baseline CAC score. Thirty-five of the 97
      women (36%) were taking estrogen plus progestin, with an annual increase in
      calcium scores of 24%+/-23%, similar to the non-HRT women (22%). Those women
      taking estrogen replacement only (n=62) was 63% lower (9%+/-22%). CONCLUSIONS:
      This is an observational study, and the results are in accordance with the
      recently published WHI study, demonstrating no benefit of estrogen plus progestin
      compared with no therapy. However, women taking unopposed estrogen demonstrated a
      significant slowing of subclinical atherosclerosis compared with non-HRT and
      estrogen plus progestin.

PMID- 15989414
TI  - Women with diabetes have poorer control of blood pressure than men.
AB  - OBJECTIVE: Diabetes is associated with a higher coronary heart disease (CHD)
      mortality in women compared with men. Less aggressive control of the CHD risk
      factors in women can contribute to this excess mortality. Because hypertension
      has a high prevalence in subjects with diabetes, we compared the control of this
      risk factor between men and women. METHODS: This was a retrospective cohort study
      comparing blood pressure levels and trends over a 1-year period between men and
      women with diabetes receiving primary care. Using a chronic disease registry
      database, subjects with type 1 and type 2 diabetes, aged >or=18, were identified
      for inclusion. Mean weighted systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) were calculated for subjects with multiple longitudinal readings.
      Subjects were classified into four blood pressure control categories based on the
      mean weighted blood pressure. Comparisons were made between men and women before
      and after controlling for baseline characteristics. RESULTS: A total of 3181
      subjects (46% women) were included in the study. More women than men were in the
      moderate and severely elevated blood pressure categories (40% and 6% compared
      with 32% and 5%, respectively, p<0.001). The unadjusted mean SBP was 3 mm Hg
      higher in women (139 mm Hg in women compared with 136 in men, p<0.001). These
      differences remained significant after controlling for baseline variables.
      CONCLUSIONS: In subjects with diabetes receiving medical care, women had poorer
      control of blood pressure and a significantly higher mean SBP compared with men.
      These findings might partially explain the excess CHD mortality in women with
      diabetes.

PMID- 15989415
TI  - Preferences and practices related to vaginal lubrication: implications for
      microbicide acceptability and clinical testing.
AB  - BACKGROUND: Research on vaginal microbicides for HIV prevention is progressing
      rapidly; the first large-scale effectiveness trials were launched in 2004. The
      majority of candidate microbicides are formulated as gels, which will act as
      lubricants when used during sex. Preferences and practices regarding lubrication
      during sex, therefore, likely influence microbicide acceptability and use.
      Researchers seek to maximize consistent and correct use of candidate microbicides
      during clinical trials to enable valid estimates of product effectiveness, and if
      proven effective, microbicides will be widely used only if acceptable. METHODS:
      We conducted a comprehensive literature review and interviewed 13 key informants
      from nine countries in Africa, Asia, Latin America, and North America. RESULTS:
      We found that norms and practices regarding lubrication during sex exist in many
      different countries. Despite significant variation, common themes emerged. In the
      majority of countries, women's genital hygiene is highly valued, and women are
      expected to achieve a moderate amount of vaginal lubrication during sex that is
      neither excessive nor inadequate. Women may try to achieve this by engaging in a
      wide variety of vaginal practices. CONCLUSIONS: Even though some informants
      expressed concerns about the acceptability of lubricating microbicides in some
      settings, they thought that microbicides should be developed, that women and men
      may be willing to accept a certain level of increased lubrication in exchange for
      protection from HIV, and that lubricating microbicides may be considered more
      acceptable when perceived as genital hygiene products. Recommendations are made
      on how to take vaginal practices into account during clinical testing of
      microbicides.

PMID- 15989416
TI  - Electroacupuncture in obese women: a randomized, controlled pilot study.
AB  - OBJECTIVE: To compare the effects of electroacupuncture and sit-up exercise on
      reducing body weight (BW) and waist circumference (WC) among obese women.
      METHODS: A randomized, controlled clinical trial was conducted from July 1, 2002,
      to June 30, 2003, in the outpatient department of Taipei Hospital, Taiwan. The
      subjects were 72 obese women, with WC>90 cm and body mass index (BMI)>30 kg/m2
      and who had not received any other weight control maneuver within the prior 3
      months. The subjects were randomly divided into groups A, B, and C. Group A
      (n=22) received electroacupuncture, group B (n=20) was assigned sit-up exercises,
      and group C (n=21) received no intervention. All three treatments lasted for 6
      weeks. The measurements of BW, BMI, and WC were performed in the beginning and
      after 6 weeks. The data were compared and expressed as percent reductions.
      RESULTS: Electroacupuncture showed significantly greater percent reductions in BW
      (p=0.009, 0.004), BMI (p=0.008, 0.016), and WC (p=0.013, 0.006) compared with sit
      up exercises or no intervention. CONCLUSIONS: In this pilot study,
      electroacupuncture treatment was more effective than situp exercise or no
      intervention in reducing BW, BMI, and WC.

PMID- 15989417
TI  - Living in fear of experiencing physical and sexual abuse is associated with
      severe depressive symptomatology among young women.
AB  - PURPOSE: To analyze the relationship among fear of being abused, direct
      experience of physical and sexual abuse, and severe depressive symptoms among
      young women. METHODS: A cross-sectional survey was conducted in schools and
      households among 3615 young Hungarian women, ages 15-24 years, of whom 2016 were
      students. A multistage stratified sampling method was applied. The shortened Beck
      Depression Inventory (BDI) and the modified Abuse Assessment Screen were used.
      Odds ratios (ORs) were calculated, and a general linear model was used to test
      effects of variables on the BDI score. RESULTS: Severe depressive symptoms were
      significantly more common among women who were abused physically (OR=3.474, 95%
      CI 2.170-5.562) or sexually (OR=6.436, 95% CI 3.085-13.429) in the past year or
      abused by a partner (OR=3.167, 95% CI 1.806-5.554) or important person (OR=2.989,
      95% CI 1.922-4.648) during their lifetime. Severe depressive symptoms were also
      found among those young women who reported feeling fearful of someone in the
      family (OR=5.027, 95% CI 2.805-9.012) or in their environment (OR=3.779, 95% CI
      2.120-6.738). In a linear regression analysis, fear of someone in the environment
      or family had the strongest effect on BDI scores after controlling for frequent
      anxiety. CONCLUSIONS: Not only the direct lifetime experience of abuse but also
      the presence of fear of abuse is associated with severe depressive symptomatology
      among young women. Fear of abuse is also an important factor to take into
      consideration in assessing young women with depressive symptoms.

PMID- 15989418
TI  - Potential testosterone therapy for hypogonadal sexual dysfunction in women.

PMID- 15989420
TI  - Martin Tabler, Ph.D. June 20, 1956-April 3, 2005.

PMID- 15989421
TI  - A society of our own.

PMID- 15989422
TI  - Blocking mouse MMP-9 production in tumor cells and mouse cornea by short hairpin
      (sh) RNA encoding plasmids.
AB  - In this study, we assessed the efficacy of the specific knockdown of matrix
      metalloprotein-9 (MMP-9) in vitro and in vivo using short hairpin RNA (shRNA)
      against MMP-9. Two plasmids were generated encoding shRNA (pshRNA) targeted
      against two distinct MMP-9 gene sequences. Transfection of these pshMMP-9s could
      be shown to specifically inhibit MMP-9 expression both in vivo and in vitro. The
      effect occurred in vitro both in cells that endogenously produce MMP-9 and in
      cells exogenously transfected with an MMP-9-encoding plasmid. Using an in vivo
      transfection approach, the pshMMP- 9 was also effective at inhibiting MMP-9
      protein expression in the mouse cornea. pshMMP-9s were also tested against herpes
      simplex virus (HSV) in the cornea. Delivery of the pshMMP-9 stopped angiogenesis
      and decreased the severity of herpetic keratitis. However, interferon-alpha (IFN
      alpha) and IFN- beta induced by pshRNA might also contribute to inhibition of
      herpetic simplex keratitis (HSK) in the cornea.

PMID- 15989423
TI  - Therapeutically promising PNA complementary to a regulatory sequence for c-myc:
      pharmacokinetics in an animal model of human Burkitt's lymphoma.
AB  - In Burkitt's lymphoma (BL) cells c-myc is often translocated in proximity to the
      Emu enhancer of the Ig gene locus. This translocation causes c-myc
      hyperexpression and an increase in the cells' proliferative capacity. A peptide
      nucleic acid (PNA) complementary to enhancer Emu intronic sequence (PNAEmu),
      linked to a nuclear localization signal (NLS), selectively and specifically
      blocks the expression of the c-myc oncogene under Emu control in vitro,
      suggesting potential therapeutic use. To explore this issue further, we have
      determined the pharmacokinetics of (14)C-labeled PNAEmu in SCID mice where a
      human tumor is established by inoculation of cells from a BL cell line. The data
      demonstrate that the compound has a relatively long life in vivo in tissues and,
      in particular, in BL tumor mass. Furthermore, in this animal model, PNAEmu shows
      low or no toxicity. All these results are in favor of a successful preclinical
      application in a BL human tumor animal model of a PNA targeting a regulatory,
      nontranscribed DNA sequence that can selectively inhibit the hyperexpression of a
      translocated gene linked to neoplastic cell expansion.

PMID- 15989424
TI  - Intracerebral and intrathecal infusion of the TGF-beta 2-specific antisense
      phosphorothioate oligonucleotide AP 12009 in rabbits and primates: toxicology and
      safety.
AB  - Here, we provide first evidence that long-term continuous infusion of highly
      purified antisense phosphorothioate oligodeoxynucleotides (S-ODN) into brain
      parenchyma is well tolerated and thus highly suitable for in vivo application. AP
      12009 is an S-ODN for the therapy of malignant glioma. It is directed against
      human transforming growth factor-beta (TGF-beta2) mRNA. In the clinical setting,
      AP 12009 is administered intratumorally by continuous infusion directly into the
      brain tumor. In view of this clinical application, the focus of our data is on
      local toxicology studies in rabbits and monkeys to evaluate the safety of AP
      12009. AP 12009 was administered either by intrathecal bolus injection into the
      subarachnoidal space of the lumbar region of both cynomolgus monkeys and rabbits
      or by continuous intraparenchymatous infusion directly into the brain tissue of
      rabbits. Intrathecal bolus administration of 0.1 ml of 500 microM AP 12009 showed
      neither clinical signs of toxicity nor macroscopically visible or
      histomorphologic changes. After a 7-day intraparenchymatous continuous infusion
      of 500 microM AP 12009 at 1 microl/h in rabbits, there was no evidence of
      toxicity except for local mild to moderate lymphocytic leptomeningoencephalitis.
      Additionally, AP 12009 showed good tolerability in safety pharmacology as well as
      in acute toxicity studies and 4-week subchronic toxicity studies in mice, rats,
      and monkeys. This favorable safety profile proves the suitability of AP 12009 for
      local administration in brain tumor patients from the point of view of
      toxicology.

PMID- 15989425
TI  - Induction of toll-like receptors and NALP/PAN/PYPAF family members by modified
      oligonucleotides in lung epithelial carcinoma cells.
AB  - ISIS 199044 is a chimeric 2'-O-methyl-containing oligonucleotide that produces
      toxicity in several cultured cell lines. Upon investigation into the mechanism of
      cytotoxicity, we discovered that treatment of lung epithelial carcinoma cells,
      A549, with ISIS 199044 and several other cytotoxic oligonucleotides induces a
      group of genes that are not normally expressed in these cells. These genes are
      involved in host response to foreign materials. Among them were toll-like
      receptor 7 (TLR7) and TLR9, members of the toll-like receptor family, responsible
      for immune response to nucleic acids and cryopyrin, a member of NALP/PAN/PYPAF
      family, which is known to assemble with ASC and regulate NF-kappaB activation and
      to modulate apoptosis. Maximal induction occurred 12-24 hours posttreatment with
      500 nM oligonucleotide in the presence of Lipofectin reagent. Furthermore, we
      have shown that this induction is chemistry dependent; it can be negated by
      certain modifications, such as replacement of 2'-O-methyl with 2'-O-methoxyethyl
      groups or substitution of phosphorothioates with phosphodiester linkages. DNA
      microarray analysis identified additional genes modulated by ISIS 199044,
      particularly genes involved in DNA damage/repair.

PMID- 15989426
TI  - Quantification of oligodeoxynucleotides in human plasma with a novel
      hybridization assay offers greatly enhanced sensitivity over capillary gel
      electrophoresis.
AB  - Capillary gel electrophoresis using UV detection (CGE-UV) has been used to
      quantify oligodeoxynucleotides (ODN) in human plasma. Although the sensitivity of
      this method is adequate to detect antisense ODN, which are administered in daily
      doses up to 10 mg/kg, CGE-UV is not sensitive enough to detect the much lower
      quantities of ODN administered for other purposes, such as immune stimulation by
      CpG ODN. We have developed a very sensitive colorimetric hybridization assay that
      increases the sensitivity of detection by more than four logs compared with CGE
      UV. The hybridization assay uses sequence-specific capture and detection ODN
      probes complementary to portions of the ODN sequence. Herein we provide a
      prototype for assay development and validation using a 24- mer immunostimulatory
      phosphorothioate ODN. Probes were locked nucleic acids (LNA), resulting in
      increased sensitivity and specificity. The linear range of the assay is 7.8-1000
      pg/ml, with a 7.8 pg/ml lower limit of quantification (LLOQ) and a detection
      limit of 2.8 pg/ml. This translates to detection of 40 attamoles. Intraassay and
      interassay precision were < or =5.0% CV and < or =12.9% CV, respectively, for
      quality control samples. The assay is suitable for a variety of matrices,
      including monkey and rat plasma, allowing application to toxicokinetic samples.
      The methodology is highly specific, with the ability to distinguish almost all
      single-base mismatched ODN. The assay detects 100% of the parent as well as some
      metabolites up to N-4, which are known to be the primary metabolites forming in
      the first hours after in vivo administration and are physiologically active with
      in vitro assays.

PMID- 15989427
TI  - Application of small interfering RNA (siRNA) for modulation of airway epithelial
      gene expression.
AB  - Small interfering RNA (siRNA) was developed as a novel tool to inhibit gene
      function in human disease. The aim of the present study was to modify the
      function of NF-kappaB in airway epithelial cells by application of siRNA. 1HAEo
      cells were transfected with siRNA directed to the p65 subunit of NF- kappaB
      (siRNA.p65). Application of siRNA.p65 caused decreased levels of p65 mRNA or
      protein after 72 hours, as determined by quantitative RT-PCR or Western blot
      analysis. The tumor necrosis factor- alpha (TNF-alpha)-induced release of
      interleukin-6 (IL-6) and IL-8 was significantly inhibited by the application of
      siRNA.p65. Well-differentiated primary cells were resistant to transfection with
      siRNA.p65. However, when undifferentiated primary cells were transfected, an
      effect of the siRNA could still be observed when the cells were differentiated in
      an air-liquid interface culture system. In conclusion, siRNA can be used to
      regulate the activity of NF-kappaB in airway epithelial cells.

PMID- 15989428
TI  - Inducible H1 promoter-driven lentiviral siRNA expression by Stuffer reporter
      deletion.
AB  - Introduction of 19-23-bp small interfering RNA (siRNA) into mammalian cells has
      become a standard procedure to downregulate mRNA with high efficacy. siRNAs can
      be introduced into cells either as synthetic duplexes or as hairpin structures
      produced by Pol III promoter-driven vectors. Pol III promoter-expressed small
      hairpin RNAs (shRNAs) offer a great possibility for the production of endogenous
      siRNA, which can be used for stable siRNA production in vivo. A major drawback of
      this strategy is the incapability of detecting rapidly occurring cellular
      responses. Here, we present a lentiviral shRNA-producing vector system, which can
      be induced by CRE recombinase enzyme to overcome these limitations. Following the
      addition of CRE, the pLIND (LentiINDucible) will activate siRNA production by
      deleting EGFP and a stop cassette between the promoter and siRNA oligo. Target
      gene downregulation capacity was comparable to that of a noninducible siRNA
      system.

PMID- 15989430
TI  - Reduction mammoplasty in an HIV-positive woman.
AB  - Mortality rates have decreased in medically compliant patients with HIV. More HIV
      positive patients are requesting procedures that improve their quality of life.
      Reduction mammoplasty has been proven to predictably relieve back, neck, and
      shoulder pain related to macromastia. A case report is presented demonstrating an
      HIV patient who underwent a reduction mammoplasty for symptomatic macromastia.

PMID- 15989431
TI  - Hepatic steatosis and HIV infection.
AB  - There is increasing concern that patients with chronic HIV infection may be at
      increased risk of nonalcoholic fatty liver disease (NAFLD), which can evolve into
      nonalcoholic steatohepatitis (NASH) and cirrhosis. Multiple factors have been
      hypothesized to be necessary for the development and progression of this
      condition. Potential risk factors, which tend to accumulate in the HIV-positive
      population, include metabolic derangements, chronic inflammation, hepatitis
      coinfection, and treatment with certain nucleoside reverse transcriptase
      inhibitors (NRTIs). HIV-associated conditions such as hyperlactatemia and
      lipodystrophy frequently overlap with fatty liver disease. The cornerstone of
      management of HIV-associated fatty liver disease is currently to treat the
      predominant underlying condition. There is a need for more epidemiologic data to
      better define the role of comorbidities and drugs in the development of NAFLD.
      Further work is also needed to elucidate the pathogenesis and to evaluate the
      therapeutic effect of treating comorbidities and avoiding certain antiretroviral
      drugs.

PMID- 15989432
TI  - Antiretroviral treatment considerations in Latino patients.
AB  - Latinos in the United States have been disproportionately affected by HIV, with a
      higher rate of infection, later diagnosis, and a higher death rate than
      Caucasians. Complicating the issue is that "Latino" is a broad term that
      encompasses diverse ethnic and racial groups, requiring a targeted approach to
      prevention and management of HIV infection. This article explores the
      demographics of HIV infection among Latinos in the United States, discusses
      cultural beliefs among Latinos that have an impact on prevention and access to
      care, and reviews strategies for managing HIV infection in this population.

PMID- 15989433
TI  - Human herpesvirus-8 seropositivity and clinical correlations in HIV-1-positive
      and highly exposed, persistently HIV-seronegative individuals in Greece.
AB  - The prevalence of anti-human herpesvirus 8 (HHV-8) antibodies was retrospectively
      assessed in a cohort of 248 consecutive HIV-1-positive patients followed up in an
      academic unit in Greece during a 14-year period and in 46 highly exposed,
      persistently HIV-seronegative (HEPS) individuals. The impact of the initial anti
      HHV-8 status on tumorgenesis and mortality was studied. The first available serum
      sample from the department's pool was tested. Demographics and data regarding
      history of sexually transmitted diseases, Hepatitis B surface antigen (HbsAg) and
      hepatitis C (HCV) status were collected. Patients who developed either HHV-8
      related or non-HHV-8-related neoplasms during long-term follow-up were also
      identified. Forty-eight percent of the HIV-1-positive patients and 56% of the
      HEPS subjects were found anti-HHV-8-positive. No difference was observed
      regarding the development of HHV-8-related or non-HHV-8-related neoplasia and
      mortality on grounds of initial anti- HHV-8 status. Mortality was positively
      associated with the presence of HBsAg. HCV infection showed a trend to be more
      common in anti-HHV-8-positive patients. In summary, the seroprevalence of HHV-8
      among HIV-1-positive patients is higher than the one reported in the Western
      world. The initial anti-HHV-8 status is not a prognostic factor in HIV-1-positive
      individuals. The high seroprevalence in HEPS individuals possibly reflects their
      risk-prone lifestyle. HbsAg-positive status is a long-term negative prognostic
      factor in HIV infection.

PMID- 15989434
TI  - Theory- and evidence-based intervention to improve adherence to antiretroviral
      therapy among HIV-infected patients in the Netherlands: a pilot study.
AB  - The objectives of this study were to describe and pilot-test a theory- and
      evidence-based intervention to improve adherence of HIV-infected patients with
      antiretroviral medication. Twenty-six treatment-experienced patients (>6 months
      on treatment) participated in a within-subject comparison design. Adherence was
      measured electronically with Medication Event Monitoring System (MEMS) caps for
      at least 5 months: 2 months before the intervention and 3 months during the
      intervention. MEMS data were used to measure the outcome of the intervention, but
      also served as feedback to participants during the intervention. Mean adherence
      during the month before intervention was compared to mean adherence during the
      third month of intervention. Data for the process evaluation were gathered
      through direct observation and semi-structured interviews. Adherence improved
      significantly during the intervention (Z = -2.1, p < 0.05). Mean adherence
      (percentage of prescribed doses taken within correct time interval) before the
      intervention was 81.8% compared to 92.5% during the third month of the
      intervention. More than 65% of the nonadherent patients (<95% adherence) before
      the intervention were adherent during the third month of the intervention. Both
      health care professionals and patients positively evaluated the intervention
      protocol and the electronic measurement of adherence. The only critique from some
      patients was the lack of userfriendliness of the MEMS cap and its medication
      container (size and shape). It can be concluded that the proposed intervention
      fits in standard care procedures, can be executed by trained HIV nurses, seems to
      improve adherence to antiretroviral medication, and is positively evaluated by
      the users. Large-scale and long-term research is warranted.

PMID- 15989435
TI  - Predictors of changes in health-related quality of life among men with HIV
      infection in the HAART era.
AB  - In a prospective cohort study between February 2001 and January 2004, baseline
      and 12-month follow-up data were collected on 226 and 197 men with HIV infection
      at three infectious disease clinics in a southern state, respectively. While many
      studies have provided important information on the correlates of health-related
      quality of life (HRQOL) during HIV infection, little research attention has been
      directed toward examining the impact of factors on change in HRQOL over time.
      This study evaluated changes in HRQOL, and examined whether baseline active
      coping, family social support, depressive symptoms and CD4 cell counts predicted
      HRQOL changes over time among men with HIV infection. Patients' HRQOL, social
      support and depressive symptoms were measured with the HIV Cost and Services
      Utilization Study tool, Coping with HIV Questionnaire, Social Support Appraisals
      Scale, and Centers for Epidemiological Studies Depression instrument.
      Multivariate linear regression analyses were conducted to determine the time
      related effects of the psychosocial variables and CD4 cell counts on each HRQOL
      dimension. Our results indicated that higher family support and CD4 cell counts
      at baseline were predictive of improved changes in physical and social
      functioning over time, and higher depressive symptoms at baseline were predictive
      of diminished role functioning, emotional well-being, and general health
      perception. These findings underline the importance of enhancing family social
      support, identifying and treating depression, and improving immune function to
      optimize HRQOL among men with HIV infection.

PMID- 15989436
TI  - Linking HIV-infected persons of color and injection drug users to HIV medical and
      other services: the California Bridge Project.
AB  - Our objectives were to describe the strategies and successes in linking out-of
      treatment HIV-infected persons of color and injection drug users (IDUs) to a
      comprehensive HIV care, treatment, and prevention program and other community
      services. Peer-based outreach staff at 21 sites throughout California provided
      assessments and referrals to 1453 persons living with HIV but without routine
      care. A linkage was defined as the receipt of a referred service. Half (49.7%) of
      persons of color and 41.6% of IDUs received services at a California Early
      Intervention Program (EIP) site after the date of first contact with peer staff;
      58.1% of clients referred to EIP were linked to the program. IDUs were less
      likely to link to EIP. However, IDU clients were less likely to be referred to
      EIP, and more likely to be referred and linked to other community programs.
      Interventions such as the California Bridge Project can effectively link HIV
      infected persons from marginalized populations to care, treatment, and prevention
      services. Programs that address immediate needs such as housing are more
      appealing to IDUs than programs offering HIV medical care.

PMID- 15989437
TI  - Pregnancy category change for efavirenz.

PMID- 15989438
TI  - New web site on HIV and TB.

PMID- 15989439
TI  - Minimizing minimally invasive surgery: the 5-mm trocar laparoscopic pyeloplasty.
AB  - BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty has evolved into the procedure
      of choice when definitive repair of the obstructed ureteropelvic junction is
      contemplated. Its main advantage over the gold standard of open pyeloplasty is
      decreased morbidity. We have utilized only three 5-mm ports in our last 15
      pyeloplasties in an effort to further reduce morbidity and improve acceptance by
      an often-younger patient population. PATIENTS AND METHODS: Fifteen consecutive
      patients underwent laparoscopic transperitoneal pyeloplasty by the 5-mm port
      technique. Three trocars were utilized, two for the working instruments and one
      for a 5-mm telescope mounted on a voice-activated robotic arm (AESOP; Intuitive
      Surgical, Sunnyvale, CA). Three patients required an additional trocar for liver
      retraction. All patients underwent dismembered pyeloplasty and had indwelling
      double-pigtail stents placed for 4 to 6 weeks. RESULTS: The mean operative time
      was 195 minutes (range 120-240 minutes). The average blood loss was 30 mL. None
      of our patients required open conversion. With a median follow-up of 10 months
      (range 3-15 months), all 15 patients have shown both subjective (freedom from
      symptoms) and objective (renal scan) improvement. CONCLUSION: We believe our
      technique has further minimized the morbidity of laparoscopic pyeloplasty without
      compromising the outcome. The 5-mm trocars obviate fascial closure, decrease
      patient discomfort, and improve cosmesis. Furthermore, the use of the robotic arm
      eliminates the need for a surgical assistant and makes this an essentially "one
      person" procedure.

PMID- 15989440
TI  - Laparoscopic adrenalectomy for large adrenal tumors.
AB  - BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy remains a controversial
      procedure for large tumors. We examined the outcome and complications of
      laparoscopic adrenalectomy for such lesions. PATIENTS AND METHODS: A total of 178
      patients underwent laparoscopic adrenalectomy, of whom 29 patients had large (>or
      =5 cm) tumors. Their mean age was 47.9 years (range 21-72 years), and the mean
      tumor size was 6.5 cm (range 5.0-11.0 cm). They were compared with patients whose
      adrenal tumors were <5 cm. RESULTS: The large-tumor group had a mean operating
      time of 176 +/- 48 minutes (range 84-278 minutes) and a mean blood loss of 136.6
      mL (range 10-800 mL) and required a mean of 1.8 days before starting oral intake.
      None of these values is significantly different from the results in the control
      group (P > 0.05). The length of recovery was significantly longer in the large
      tumor group (5.4 v 4.5 days; P < 0.05), but this was not true if a patient with a
      23-day postoperative stay is excluded. The overall incidence of complications was
      12% in the large-tumor group, which was not significantly different from that in
      the control group (P > 0.05). CONCLUSIONS: The operating time, blood loss, and
      incidence of complications after laparoscopic adrenalectomy did not differ
      between the patients with large and small adrenal tumors, indicating that
      experienced surgeons can safely and effectively use laparoscopy for larger
      tumors. However, it is necessary to consider carefully whether laparoscopic
      surgery is indicated for tumors that show infiltration on preoperative imaging or
      for patients who have undergone previous upper-retroperitoneal surgery.

PMID- 15989441
TI  - Validity of the MISTELS simulator for laparoscopy training in urology.
AB  - BACKGROUND AND PURPOSE: The McGill Inanimate System for Training and Evaluation
      of Laparoscopic Skills (MISTELS) consists of a series of five laparoscopic
      exercises performed in an endotrainer box. MISTELS has been validated for use in
      both training and evaluation of general surgery residents in fundamental
      laparoscopic skills. The purpose of this study was to demonstrate the construct
      validity of MISTELS for urology residents. SUBJECTS AND METHODS: Seventeen
      participants were evaluated during performance of the five MISTELS tasks (peg
      transfer, pattern cutting, ligating loop, and suturing with extracorporeal and
      intracorporeal knots) using the standardized scoring system, which rewards both
      speed and precision. Participants included 13 urology residents (PGY 1-5), 1
      fellow, and 3 urologists experienced in laparoscopy. Results are expressed as
      median (range). The Mann-Whitney U-test was used to compare MISTELS scores for 9
      novice (PGY 1-4) and 8 experienced urologists (PGY 5-attending). P < 0.05 was
      considered statistically significant. RESULTS: The median MISTELS total
      normalized score for novices was 52.3 (range 15-68.9) compared with 71.7 (range
      56.3-82.9) for experienced urologists (P = 0.007). Although the experienced group
      achieved higher scores in all five individual tasks, statistically significant
      differences were demonstrated for the peg transfer and intracorporeal suture
      tasks only. CONCLUSION: These data provide evidence for construct validity of the
      MISTELS system for urology residents.

PMID- 15989442
TI  - Can the need for palliative transurethral prostatic resection in patients with
      advanced carcinoma of the prostate be predicted?
AB  - PURPOSE: To identify the factors predicting the need for palliative transurethral
      resection of the prostate (channel TURP) in patients with advanced carcinoma of
      the prostate (CAP) receiving androgen ablation therapy. PATIENTS AND METHODS:
      From January 1996 to January 2004, 203 patients with advanced CAP were treated by
      androgen ablation. Patients presenting with retention were catheterized
      initially, and those (N = 12) who failed a catheter-free trial and had immediate
      channel TURP were excluded. The remaining 191 patients were followed every 3
      months (mean 35.5 months, range 6-92 months). Patients requiring channel TURP
      (group 1; N = 42 [22%]) during follow-up were compared with those who did not
      (group 2) for predictive factors, viz. retention of urine, serum prostate
      specific antigen (PSA) concentration, Gleason sum, prostate size, and bony
      metastasis at presentation. RESULTS: Channel TURP was performed at a mean of 21
      months (range 3-72 months). The mean Gleason sum in this group was 7.88, whereas
      it was 7.29 in group 2 (P = 0.013). Retention at presentation was significantly
      more common in group 1 (N = 26; 61.9%) than in group 2 (N = 46; 30.8%; P =
      0.001). Patients who did not present with retention and had Gleason sums < or =7
      (N = 32) did not require channel TURP. Of the 14 patients who voided successfully
      after a catheter-free trial but had Gleason sums of >7, 71.4% required channel
      TURP. Other factors were not found to be significantly different in the two
      groups. CONCLUSION: High Gleason sum and retention at presentation are
      significant factors predictors of the need for channel TURP during follow-up in
      patients with advanced CAP receiving androgen ablation therapy.

PMID- 15989443
TI  - Change in serum prostate specific antigen concentration after holmium laser
      enucleation of the prostate: a marker for completeness of adenoma resection?
AB  - BACKGROUND AND PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is a
      well-established technique for the treatment of benign prostatic hyperplasia
      (BPH). To date, changes in serum prostate specific antigen (PSA) after HoLEP have
      not been published. We hypothesized that HoLEP produces a diminution in PSA
      similar to that produced by the gold-standard therapies for BPH. To test this
      hypothesis, we have examined PSA data before and after HoLEP from two
      institutions performing high volumes of this procedure. PATIENTS AND METHODS:
      Between August 1998 and September 2004, 509 HoLEPs were performed at two
      institutions for which complete PSA data were available. Preoperative demographic
      and transrectal ultrasonography (TRUS) volume measurements were recorded;
      postoperative pathology and TRUS volume were obtained. Change in PSA as a
      function of the weight of prostate resected and the relation of preoperative TRUS
      volume to PSA was determined. RESULTS: The average weight of adenoma resected was
      49.8 g (range 5-300 g) in the McGill group and 90.4 g (range 7.9-312 g) in the
      Methodist Hospital group. The mean decrease in PSA was 81.7% in the McGill group
      (range 6.0-1.1 ng/mL; P < 0.0001) and 86.0% in the Methodist Hospital group
      (range 8.6-1.2 ng/mL; P < 0.0001). Log transformed preoperative PSA correlated
      well with TRUS volume (r = 0.45), as did the weight of adenoma resected with
      absolute change in PSA (r = 0.38). The TRUS volume decreased significantly, from
      111.9 cc to 26.5 cc, in the Methodist Hospital group (P < 0.0001). CONCLUSION:
      The HoLEP procedure produces a significant diminution in PSA that correlates well
      with the weight of adenoma resected. Measurement of PSA may be a useful tool for
      the objective assessment of ablative therapies for BPH, as the reduction in PSA
      corresponds well with the amount of adenoma removed.

PMID- 15989445
TI  - Report on the basic research session.

PMID- 15989444
TI  - Holmium laser enucleation of the prostate: a comparison of efficiency measures at
      two institutions.
AB  - BACKGROUND AND PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is
      perceived to be technically difficult, time consuming, and inefficient. We
      assessed the efficiency of HoLEP by documenting the technical features of the
      procedure at two hospitals located on different continents. PATIENTS AND METHODS:
      A retrospective analysis of all patients who underwent HoLEP at the Methodist
      Hospital of Indiana and Tauranga Hospital in New Zealand was performed. A series
      of 40 patients from the Indiana cohort were pair-matched, by the weight of
      prostate tissue retrieved, with 40 patients from the New Zealand cohort.
      Enucleation time and morcellation time were compared in the two groups. RESULTS:
      The mean weight of the tissue retrieved from the Indiana cohort was 27.1 g and
      that from the New Zealand cohort was 22.9 g (P = 0.41). The mean enucleation
      times were 47.6 minutes and 29.2 minutes, respectively (P < 0.001). The mean
      morcellation times were 9.9 minutes and 7.7 minutes (P = 0.201). The mean rates
      of enucleation were 0.58 g/min and 0.71 g/min (P = 0.17). The mean rates of
      morcellation were 3.4 g/min and 4.3 g/min (P = 0.20). The HoLEP efficiency
      increased as a function of gland size (R(2) = 0.56). CONCLUSIONS: Holmium laser
      enucleation of the prostate is a reproducible technique, as there is little
      variation in efficiency from one surgeon to another. Furthermore, the efficiency
      of HoLEP increases as prostate size increases, which suggests that HoLEP may be
      an ideal treatment for men with large prostates.

PMID- 15989446
TI  - Comparison of Peditrol irrigation device and common methods of irrigation.
AB  - BACKGROUND AND PURPOSE: The Peditrol is a novel hands-free irrigation device that
      delivers a bolus of irrigant through the ureteroscope when the foot pedal is
      deployed. The purpose of this study was to compare the flow and pressures created
      by the Peditrol with those of commonly used methods of irrigation. MATERIALS AND
      METHODS: Flows through a flexible 6.9F Olympus ureteroscope (F-URS) and a 7.5F
      semirigid ACMI ureteroscope (S-URS) were measured in duplicate with the working
      channel empty and with a 2.2F Nitinol basket or a laser fiber in the working
      port. Irrigant flow was pressurized by gravity drainage at 100 cm H(2)O (GI),
      pressurized irrigant bag at 300 cm H(2)O (PI), handheld 60-cc syringe (HS), and
      the Peditrol. A 20-gauge angiocatheter was placed through the parenchyma into the
      renal pelvis of an ex-vivo cadaveric porcine kidney and attached to a pressure
      transducer. Pressures were measured in triplicate using the same irrigation
      techniques. RESULTS: With a basket or 200-microm laser fiber in the working port
      of the F-URS, Peditrol mean flows were superior to those of PI (3.3 and 6.3
      times, respectively; P < 0.001) but similar to those of HS (0.7 to 1.1 times).
      All irrigation types resulted in intrarenal pressures greater than gravity
      irrigation (P < 0.05). The Peditrol demonstrated intrapelvic pressures <40 cm
      H(2)O when used with a 12/14F ureteral access sheath (AS). Without an AS, the
      intrapelvic pressure reached 92 cm H(2)O, similar to the pressures reached with
      the S-URS under various irrigation conditions (84-287 cm H(2)O) and comparable to
      the HS method through the F-URS (97 cm H(2)O). CONCLUSIONS: The Peditrol
      irrigation device generates superior flow through an F-URS compared with GI or
      PI, particularly with an instrument in the working port. Intrarenal pressures
      when used with an F-URS and AS are low. When an AS is not used, the intrarenal
      pressure is similar to or lower than pressures obtained using an S-URS with
      different irrigation modalities.

PMID- 15989447
TI  - Hand-assisted laparoscopic partial nephrectomy in the porcine model using gelatin
      matrix hemostatic sealant without hilar occlusion.
AB  - BACKGROUND AND PURPOSE: Gelatin matrix hemostatic sealant (GMHS) has been used
      for hemostasis during partial nephrectomy with hilar clamping. The objective of
      this study was to determine the ability of GMHS to achieve hemostasis without
      hilar clamping in the porcine model. MATERIALS AND METHODS: In this feasibility
      study, eight farm pigs underwent a left-hand-assisted laparoscopic partial
      nephrectomy (HALPN). The lower fourth of the kidney was removed with cold
      scissors, and GMHS was applied laparoscopically. Samples were collected for
      measurement of serum hemoglobin (Hb) and creatinine (Cr) prior to surgery and at
      4 and 30 days after HALPN. The kidneys were harvested at 30 days, and retrograde
      pyelograms and pathologic analysis were performed. RESULTS: Application of GMHS
      achieved complete hemostasis in all eight animals. The mean estimated blood loss
      was 40 mL, and the operating time was short (mean 92.5 minutes). In three
      kidneys, a significant collecting system opening was noted but not repaired. At
      harvest, there were no hematomas, infections, or urine leaks in any animals. In
      one animal, a 2-cm contained fluid collection was identified. There was no
      difference in the preoperative and harvest Hb (9.63 v 9.21 g/dL; P = 0.49), but
      there was a slight increase in Cr (1.21 v 1.46 mg/dL; P = 0.01) possibly because
      of the decreased renal mass after partial nephrectomy. CONCLUSION: Even without
      hilar occlusion, GMHS was 100% safe and effective in controlling bleeding after
      HALPN in the porcine model. Avoidance of hilar occlusion may reduce the risk
      associated with warm renal ischemia and the extra dissection required to isolate
      the hilum in preparation for clamping.

PMID- 15989448
TI  - Evaluation of superficial bladder transitional-cell carcinoma by optical
      coherence tomography.
AB  - BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) is a new modality that
      allows noninvasive examination of the internal structure of biological tissue in
      vivo with a spatial resolution of 10 to 15 microm. This study evaluated the
      clinical application of OCT to determine epithelial and subepithelial anatomic
      structure and invasiveness of bladder epithelial lesions. MATERIALS AND METHODS:
      The OCT examination was performed with a 980-nm 10 mW superluminescent diode
      using a 2.7-mm-diameter optical fiber positioned cystoscopically. A total of 261
      scans of 1.5 seconds' duration, which generated 200 x 200-pixel images, were
      performed on 87 areas in 24 patients at high risk of having transitional-cell
      carcinoma (TCC). Lesions, visually suspect, and normal areas were photographed,
      scanned, and biopsied. The scans were evaluated independently before comparison
      with histopathology findings. RESULTS: Of the 87 areas, 29 of 36 visually suspect
      areas and 35 of 35 normal areas, were correctly diagnosed with OCT. Of the 16
      areas with papillary TCC, all 16 were diagnosed correctly as tumor, and 9 of 10
      were diagnosed correctly as invasive, including 6 with lamina propria invasion
      only. Papillary and flat tumors, carcinoma in situ, inflammation, chronic
      cystitis, and von Brunn's nests were scanned. Overall, OCT had a sensitivity of
      100%, overall specificity of 89%, positive predictive value of 75%, and negative
      predictive value of 100%. The accuracy was 92%. The positive predictive value for
      invasion was 90%. CONCLUSION: Optical coherence tomography is a simple, portable,
      promising modality for evaluation of bladder lesions and depth of tumor
      penetration. Further refinement of this technology may lead to the development of
      an optical surrogate for biopsy.

PMID- 15989449
TI  - Radial dilation of ureteral balloons: comparative in vitro analysis.
AB  - BACKGROUND AND PURPOSE: The dynamics of ureteral balloon expansion may differ
      with increasing extrinsic compressive forces and inflation pressures. This study
      compared the ability of ureteral balloons to expand under different conditions.
      MATERIALS AND METHODS: The balloons tested were the Cook Accent, Ascend, Ascend
      AQ, and Pursuit; the Bard 195503 and UroForce; and the Boston Scientific
      Microvasive UroMax Ultra. When available, multiple balloon diameters and lengths
      were tested. With a guidewire in place, the balloon tip was secured by elevated
      vise grips on either side of the balloon. A string was wrapped around the balloon
      center once, and incremental increases in load were added (2 g, 42 g, 82 g, 122
      g) to represent increasing extrinsic compression. The balloon was inflated with
      contrast medium, and circumference changes were measured at increments of 2 atm
      up to burst pressure. Balloons were tested in triplicate for each weight.
      RESULTS: The majority of the balloons were unable to reach 90% of their expected
      diameter with larger constrictive loads (122 g) at low inflation pressure (4
      atm). The only balloons that achieved a diameter at 4 atm that was at least 90%
      of the expected diameter with a coefficient of variance (CV) of <10% at all
      radial loads were the Pursuit 6 mm x 4 cm (98.2 +/- 2.2%; CV 7.88%), UroMax Ultra
      7 mm x 4 cm (97.5 +/- 1.4%; CV 5.94%), and the UroMax Ultra 7 mm x 6 cm (101 x
      1.2%; CV 7.67%). At inflation burst pressure, the balloons able to maintain a
      diameter at or above 100% of expected with a CV of <5% at burst pressure were the
      Ascend AQ 4 mm x 4 cm (116 +/- 1.0%; CV 3.34%) and the Pursuit 6 mm x 4 cm (108
      +/- 2.0%; CV 4.53%). CONCLUSION: Reaching maximum inflation diameter at low
      pressures in the face of increasing extrinsic compression may help minimize the
      risk of ureteral injury. Reliable expansion to maximum diameter even with higher
      extrinsic compressive forces is another important characteristic of ureteral
      balloons. Balloon material, configuration, and dimensions may contribute to
      differences in dilation properties.

PMID- 15989450
TI  - Monitoring radiofrequency renal lesions in real time using contrast-enhanced
      ultrasonography: a porcine model.
AB  - BACKGROUND AND PURPOSE: Ablation by cold (cryoablation) or radiofrequency energy
      (RFA), has been popularized for the treatment of small renal tumors. Regrettably,
      there currently is no reliable method of radiologically monitoring the
      propagation of RF lesions in real time. Ultrasonography enhanced by gas-filled
      microbubble contrast agents allows depiction of regions of tissue perfusion and
      has been described as a useful adjunct in diagnosing renal pseudotumors,
      improving prostate biopsy results, and confirming successful ablation of liver
      tumors. We hypothesized that contrast-enhanced ultrasonography (CEUS) would allow
      us to define, in real time, areas of cell death secondary to RFA and thus
      determine successful treatment. MATERIALS AND METHODS: Five female swine
      underwent initial laparoscopic exploration and creation of ipsilateral upper- and
      lower-pole renal RFA lesions. Lesion size was measured with standard gray-scale,
      Doppler, and microbubble CEUS. After 2 weeks, an identical procedure was
      performed on the contralateral kidney, including repeat sonographic measurements
      on the first kidney. All swine were then immediately sacrificed, and both kidneys
      (20 lesions) were harvested for pathologic analysis (hematoxylin-eosin and
      nicotinamide adenine dinucleotide stains). Radiographic lesion size was then
      compared with the gross and microscopic findings. RESULTS: The RFA lesions could
      not be imaged accurately in real time with standard gray-scale or Doppler
      sonography. However, microbubble CEUS was able to monitor parenchymal blood flow
      and, thus, the lesions (no blood flow) in real time. Hypoechoic lesions (no
      bubble enhancement) imaged during contrast sonography corresponded with regions
      of cell death as demonstrated on pathologic analysis. CONCLUSIONS: Microbubble
      CEUS is can monitor RFA lesions in real time. This novel imaging modality should
      allow more effective renal tumor ablation.

PMID- 15989451
TI  - A new SWL titanium stent (Zebra Stent): resistance to shockwave exposure.
AB  - BACKGROUND AND PURPOSE: Recently, a new-concept lumen-less Teflon-coated double-J
      wire stent (Zebra stent) has been introduced to facilitate residual stone
      clearance, in particular after SWL. Its metal core expresses highly mismatched
      acoustic impedance. It was the aim of this study to exclude damage to the stent
      through shockwaves. Also, its Teflon coating should to some degree prevent
      encrustation, and stents removed from stone formers were examined for
      encrustation. MATERIALS AND METHODS: Series of 2000 shockwaves of an average and
      a maximum energy were applied to defined areas of Zebra stents in a waterbath on
      a Siemens Multiline Lithotriptor. Stents were then examined for core and sheath
      damage by digital photography, scanning electron microscopy, and
      microradiography. In addition, two Zebra stents and one conventional double-J
      stent from two stone formers were assessed in the same way for damage and
      encrustation. RESULTS: There was no damage whatsoever to either of the stents.
      Whereas there was considerable encrustation on the conventional double-J stent,
      there was none on the Zebra stents after 4 and 5 weeks in situ. CONCLUSIONS:
      Zebra stents resist shockwaves to a maximum number and energy sufficiently to be
      applied safely under SWL. Whether they resist encrustation to a higher degree in
      the short term than conventional stents remains to be established.

PMID- 15989452
TI  - Effectiveness of eutectic mixture of local anesthetic cream and occlusive
      dressing with low dosage of fentanyl for pain control during shockwave
      lithotripsy.
AB  - BACKGROUND AND PURPOSE: To investigate the effect and usefulness of Eutectic
      Mixture of Local Anesthetic (EMLA) applied with an occlusive dressing and used
      simultaneously with a low dose of fentanyl during shockwave lithotripsy (SWL).
      PATIENTS AND METHODS: One hundred sixty patients with kidney stones, aged between
      19 and 68 years, were randomly divided into seven groups that were treated as
      follows: group 1: fentanyl 1 microg/kg by intravenous infusion (IV); group 2: IV
      fentanyl 0.25 microg/kg; group 3: occlusive dressing and IV fentanyl 0.25
      microg/kg; group 4: placebo cream and IV fentanyl 0.25 microg/kg; group 5: EMLA
      cream and IV fentanyl 0.25 microg/kg; group 6: placebo cream and IV fentanyl 0.25
      microg/kg with an occlusive dressing; and group 7: EMLA cream and IV fentanyl
      0.25 microg/kg with an occlusive dressing. The mean arterial pressure (MAP),
      heart rate, ventilatory rate, and oxygen saturation (SpO(2)) were recorded on all
      patients. A visual analog scale 0-100 mm (VAS) was used for the evaluation of
      pain. The skin integrity was inspected to detect any lesions after SWL. RESULTS:
      The SpO(2) in group 1 was lower statistically than in the other groups. The VAS
      score in group 7 was clearly lower than in the others in the first, tenth, and
      twentieth minutes and at the end of SWL. In groups 6 and 7, additional fentanyl
      doses were lower than in the other groups, but only in group 7 was the total
      fentanyl dosage low. Skin lesions were not seen only in groups 3, 6, and 7.
      CONCLUSION: Use of EMLA and an occlusive dressing with low doses of fentanyl
      during SWL provides appropriate analgesia with minimal morbidity.

PMID- 15989453
TI  - Intravenous urography in evaluation of asymptomatic microscopic hematuria.
AB  - BACKGROUND AND PURPOSE: In 2001, the American Urologic Association Best Practice
      Policy Panel recommended CT or intravenous urography (IVU) over ultrasonography
      as the initial imaging modality in patients with asymptomatic microhematuria. We
      here present results of a study initiated many years ago and completed prior to
      2001 that provides information pertinent to the use of IVU as the initial imaging
      modality for such patients. PATIENTS AND METHODS: This study compared the results
      of IVU and ultrasonography in patients 40+ years of age who were referred to a
      single urology department for evaluation of microscopic hematuria between 1994
      and 2000. There were 290 patients who agreed to participate by undergoing
      ultrasonography in addition to IVU; 247 completed both tests. There were 81 men
      and 166 women with a mean age of 56.4 years (range 40-86 years). Thirty patients
      (12%) were smokers. RESULTS: A renal lesion or mass suggestive of tumor was found
      in 8 patients (3.2%); 3 patients had this finding on the IVU examination and 5 on
      ultrasonography. None of the patients had such a lesion/mass on both
      examinations. Two patients with suspect lesions were ultimately found to have
      renal-cell carcinoma. Both of the patients with renal cancer had a suspect lesion
      on the ultrasound examination but not on the contemporaneous IVU. CONCLUSION:
      Intravenous urography may miss lesions/masses that lead to a diagnosis of upper
      tract neoplasia.

PMID- 15989456
TI  - HTLV-2 horizontal and vertical transmission in a family from a Brazilian urban
      area: seroepidemiological, clinical and molecular study.
AB  - Human T cell lymphotropic virus type 2 (HTLV-2) has been shown to be endemic in
      Brazilian Indians and among intravenous drug users in urban areas, but
      transmission of this infection seems to be infrequent in the general population
      living in urban areas in Brazil. Six persons in three generations of a Brazilian
      family were evaluated to assess HTLV-2 transmission and its molecular features in
      the positive cases. The index was detected during screening (HTLV EIA) of donated
      blood in Fundacao Hemominas, Belo Horizonte, Brazil. Confirmatory serological
      test and viral typing were performed by Western blotting and polymerase chain
      reaction. The family consisted of husband, wife (index case), three daughters,
      and the mother of the index case. The husband and one daughter were found
      positive, thus pointing to horizontal and vertical transmission. The husband was
      a truck driver, who reported casual sex during frequent traveling. The positive
      daughter was breast-fed for 3 months, as opposed to the remaining two
      (seronegative), who breast-fed for 1 month. The index case's mother was negative.
      To identify HTLV-2 subtype(s), phylogenetic analysis of the noncoding long
      terminal repeat region and part of the env and tax coding regions was performed.
      These new isolates from Belo Horizonte are related to subtype IIa but present a
      molecular variant with extended tax, previously reported in subtype IIc.
      Analyzing both LTR and env regions, the family's sequences clustered with
      isolates of Brazilian intravenous drug users and transfusion transmitted virus.

PMID- 15989457
TI  - Reasons for stopping antiretrovirals used in an initial highly active
      antiretroviral regimen: increased incidence of stopping due to toxicity or
      patient/physician choice in patients with hepatitis C coinfection.
AB  - Low adherence and toxicities among HIV-positive patients starting highly active
      antiretroviral therapy (HAART) can lead to discontinuation of therapy and
      treatment failure. Little is known about hepatitis C (HCV) status and
      discontinuation of HAART. Poisson regression was used to determine factors
      related to discontinuation of any part of an initial HAART regimen due to
      treatment failure (TF) or toxicities and patient/ physician choice (TOX), and to
      investigate the relationship between HCV and discontinuation of a HAART regimen
      in 1198 patients staring HAART after 1999 from the EuroSIDA study. At 1 year
      after starting HAART, 70% of patients remained on their original regimen, 24% had
      changed, and 6% were off all treatment. The most frequent reason for
      discontinuation was toxicities (30.4%). The incidence of any discontinuation was
      significantly lower after 1999 compared to before [incidence rate ratio (IRR)
      0.43; 95% CI 0.35-0.53, p < 0.0001], this pattern was most marked for toxicities
      (IRR 0.28; 95% CI 0.20-0.39, p < 0.0001) and patient/physician choice (IRR 0.49;
      95% CI 0.33-0.73, p < 0.0001). Patients with HCV had a higher incidence of
      discontinuation due to TOX (IRR 1.46, 95% CI 1.13-1.88, p = 0.0042) compared to
      patients without HCV. Patients with HCV were more likely to discontinue all or
      part of their HAART regimens due to toxicity or patient/physician choice.
      Managing adverse events must remain a key intervention in maintaining HAART.
      There is a need for further studies to describe the relationship between HCV,
      specific antiretrovirals, and different treatment strategies.

PMID- 15989458
TI  - Temporal trends in HIV Type 1 incidence among inner-city childbearing women in
      Atlanta: use of the IgG-capture BED-enzyme immunoassay.
AB  - Recently, we developed an immunoglobulin G (IgG)-capture BED-enzyme immunoassay
      (BED-CEIA) to identify recent HIV-1 infections. We estimated HIV-1 incidence
      among inner-city pregnant women in Atlanta, Georgia (1991-1998) using this assay.
      The annual cumulative incidence was estimated at 2.4/1000 (95% CI = 2.0-2.9).
      Incidence declined from 3.1/1000 in 1991-1994 to 1.4/1000 in 1995-1998 (risk
      ratio = 2.3, 95% CI = 1.5-3.4). Women with recent HIV-1 infection more often
      reported a previous negative antibody test (p = 0.018) and sexual relations with
      men other than the father during the past year (p = 0.046). Fewer seroconverters
      in 1995-1998 used crack cocaine than in the earlier time period. A high but
      declining HIV-1 incidence was found among inner-city pregnant women in Atlanta.

PMID- 15989459
TI  - Redistribution of human immunodeficiency virus type 1 variants resistant to
      protease inhibitors after a protease inhibitor-sparing regimen.
AB  - The redistribution of mutations related to protease inhibitor (PI) resistance
      after a PI-sparing regimen in human immunodeficiency virus (HIV)-infected, highly
      PI-experienced patients was prospectively assessed. Twenty-five patients failing
      a PI-including regimen were given PI-sparing antiretroviral therapy, and then
      followed for 24 weeks after PI resumption. Genotyping was performed by direct
      sequencing before and during the PI-sparing regimen. The median (interquartile
      range, IQR) baseline CD4+ T-lymphocyte count was 198 (120-255) cells/microl, and
      the median HIV-RNA level was 82,000 (41,000-300,000) copies/ml. Patients had
      experienced a median of 4.5 (4-5.25) PIs. The median number of PI mutations was
      eight (6-9). The PI-sparing regimen consisted of a median of three (3-4) drugs
      and lasted for a median of 53 (24-67) weeks. At the end of the study, the median
      number of PI mutations was 6.5 (6-9). The median change in the number of PI
      mutations was -1 (IQR from -1 to 0). A reduction from baseline was observed in 13
      cases (52%); nine (36%) showed no change and three (12%) showed an increased
      number of PI substitutions. In highly PI-experienced patients, a PI-sparing
      regimen may lead to a reduction, no change, or increase in the number of PI
      mutations. The reduction is negligible in most cases.

PMID- 15989460
TI  - Changes in nevirapine plasma concentrations over time and its relationship with
      liver enzyme elevations.
AB  - Liver enzyme elevations are frequently seen in patients treated with nevirapine
      (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem
      to favor the development of NVP-related liver toxicity. We have examined
      variation on NVP C(trough) over time, as well as the impact of NVP C(trough)
      concentrations and the role of chronic hepatitis C on the incidence of liver
      enzyme elevations over a 48-week study period in HIV-infected patients on NVP
      therapy. Thirty-seven patients who initiated a triple regimen of NVP (200 mg bid)
      plus two nucleoside reverse transcriptase inhibitors (NRTI) were analyzed. A
      significant increase in serum transaminase levels occurred progressively over
      time. However, no significant variations in NVP plasma C(trough) were noticed in
      48 weeks. In total population, maximum fold increase (MFI) in serum AST, ALT, and
      GGT was correlated with 24 week NVP C(trough). In HCV+ subjects, 12-week NVP
      C(trough) was closely correlated with maximum transaminase elevations, whereas in
      HCV- patients, 24-week concentrations were correlated with maximum transaminase
      increase. However, no differences in either NVP plasma C(trough) or in MFI in
      transaminase levels could be determined when comparing patients with and without
      hepatitis C at any time point.

PMID- 15989461
TI  - Immunological predictors of survival in HIV type 2-infected rural villagers in
      Guinea-Bissau.
AB  - We investigated the association between beta2-microglobulin, neopterin, serum
      levels of soluble urokinase-type plasminogen activator receptor (suPAR), CD4
      count, and plasma viremia with survival in 133 HIV-2-infected villagers and 160
      controls living in rural Guinea-Bissau. Subjects were recruited in 1991 and
      visited at home every 3-6 months until 1998. Median beta2-microglobulin,
      neopterin, and suPAR were significantly higher and CD4% significantly lower among
      HIV-2-infected individuals than controls. Thirty-one HIV-2-infected individuals
      died and 7 were lost to follow-up. beta2-Microglobulin, CD4%, and plasma viral
      load were associated independently with survival in multivariate analyses.
      Neopterin and suPAR did not reach statistical significance. These findings
      suggest that immune activation is central to the pathogenesis of HIV. They also
      have important implications for resource-poor settings where CD4 count and plasma
      viral load are unaffordable.

PMID- 15989462
TI  - Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic
      individual and potential role in virus attenuation.
AB  - Recent reports have determined that HIV-1 Vif counteracts an innate antiviral
      cellular factor, Apobec3G. However, the function of Vif during HIV-1 pathogenesis
      remains poorly understood. To gain a better understanding of Vif function, the
      viral isolate from an HIV-1-infected long-term nonprogressor (LTNP) that
      displayed a Vif-mutant replication phenotype was studied. This LTNP has been
      infected since before 1983 and has no HIV-related disease in the absence of
      antiretroviral therapy. From separate samples, obtained on more than one study
      visit, virus grew in cocultures of LTNP cells with Vif-complementing T cell
      lines, but not the parental T cell lines. An unusual amino acid motif (KKRK) was
      found in the Vif sequence at positions 90 to 93. Since this motif commonly
      functions as a nuclear localization sequence, experiments were performed to
      determine the ability of this KKRK motif to mediate nuclear localization of Vif.
      Wild-type Vif displayed a predominantly cytoplasmic distribution. In contrast,
      the KKRK Vif showed a predominantly nuclear localization. The effect of the KKRK
      mutation on virus production and infectivity was also studied. The KKRK motif
      that mislocalizes Vif to the nucleus also reduces viral replication and
      infectivity in nonpermissive cells. Our data highlight the importance of Vif in
      HIV-1 pathogenesis and also provide a unique tool to investigate the interaction
      of Vif and Apobec3G.

PMID- 15989463
TI  - Full-length HIV type 1 genome analysis showing evidence for HIV type 1
      transmission from a nonprogressor to two recipients who progressed to AIDS.
AB  - Epidemiologically-linked HIV-1 transmission cohorts serve as excellent models to
      study HIV disease progression. The actual relationship between viral variability
      and HIV disease outcome can be extrapolated only through such rare
      epidemiologically linked HIV-1-infected cohorts. We present here a cohort of
      three patients with the source termed donor A (a nonprogressor) and two
      recipients B and C. Both recipients acquired HIV through blood transfusion from
      donor A and have progressed to AIDS. By analyzing 15 near full-length HIV- 1
      genomes (8.7 kb each genome) from longitudinally collected peripheral blood cell
      samples (four time points for patient A, four for patient B, and seven from
      patient C), we were able to demonstrate transmission of HIV from donor A and
      epidemiologic linkage among members A, B, and C after 10 years of HIV infection.
      These analyses are novel in demonstrating that HIV-1-infected nonprogressing
      individuals bear the potential to transmit HIV-1 variants and that HIV variants,
      which led to a benign disease in a nonprogressor donor, were able to cause
      disease in other individuals. Overall, these studies highlight the utility of
      full genome sequencing in establishing epidemiologic linkage in a chronically
      infected HIV cohort after 10 years of initial infection.

PMID- 15989464
TI  - Genetic markers on the HTLV-1 p12I protein sequences from Brazilian HAM/TSP
      patients and asymptomatic HTLV-1 carrier isolates.
AB  - The human T cell leukemia/lymphotropic virus type-1 (HTLV-1) genome has
      approximately 9 kb and contains the pX region that codes for regulatory and
      accessory proteins. The pX ORF-I encodes for the p12 protein, a 99 aa peptide,
      which presents several functional putative domains, such as leucine zipper
      motifs, SH3- binding motifs, and a dileucine motif, p12I. Also, a rare p12IK88
      allele was found mainly in HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) patients, suggesting it is a marker of pathogenesis,
      although recent studies showed p12IK in asymptomatic HTLV-1 carriers. To extend
      the observations on p12I motifs, we sequenced 26 p12I from HAM/TSP patients and
      asymptomatic HTLV-1 carriers. Amino acid analysis of 48 p12I motifs demonstrated
      the presence of several alleles, but the allelic variation, including p12IK, was
      not prevalent in HAM/TSP isolates. Nonetheless, some genetic markers were
      recognized in association with isolates from HTLV-1a subgroup B and Brazilian
      HTLV-1aA strains.

PMID- 15989465
TI  - Enfuvirtide is active against HIV type 1 group O.
AB  - A high diversity within the HR1/HR2 regions of viral gp41 and one natural change
      (N42D) within the 36-45 aa domain in HIV-1 group O in comparison with HIV-1 group
      M isolates have led us to suspect that enfuvirtide (ENF) should not be active
      against HIV-1 group O. We analyzed in vitro and in vivo the antiviral activity of
      ENF against HIV-1 group O isolates. The IC50 at baseline was 0.15 +/- 0.028
      microg/ml in a clinically derived virus specimen. After initiating treatment with
      ENF, a significant decline in plasma HIV-RNA and CD4 gain was noticed in one
      patient. Therefore, individuals with HIV-1 group O strains might benefit from ENF
      therapy.

PMID- 15989467
TI  - Characterization of a long terminal repeat region from an infectious Indian HIV
      type 2 isolate.
AB  - An infectious Indian human immunodeficiency virus type 2 isolate from Mumbai,
      propagated in this laboratory, was found to bear an unusually short long terminal
      repeat (LTR) region. Complete sequencing of the 601 bp LTR indicated a loss of
      around 250 nucleotide pairs from the unique 3' (U3) region as compared to other
      well-characterized HIV-2 isolates. Phylogenetic analysis of this LTR shows
      closest relatedness to the Guinea-Bissau subtype A isolates HIV-2(CAM2) and HIV
      2(ALI). The LTR from the biologically active infectious clone with the observed
      deletion contained all functionally relevant promoter and polyadenylation
      sequences.

PMID- 15989466
TI  - Sequences of clustered epitopes in Gag and Nef potentially presented by
      predominant class I human leukocyte antigen (HLA) alleles A and B expressed by
      human immunodeficiency virus type 1 (HIV-1)-infected patients in Vietnam.
AB  - The aim of this study was to define pluriepitopic regions in Gag and Nef possibly
      relevant in the perspective of a vaccine design in a vietnamese population. The
      protein sequences derived from gag and nef genes and phenotyping of the class I
      human leukocyte antigens (HLA) A and B alleles were established for 28 human
      immunodeficiency virus type 1 (HIV-1)-infected patients from Ho Chi Minh City,
      Vietnam. The protein sequences display polymorphism mutations as compared with a
      B reference strain (HXB2). The most frequently represented HLA-A and -B alleles
      were HLA-A11, A02, and A33 expressed by 35.7, 23.2, and 21.4% of the patients,
      respectively, and HLA-B75, B46, and B62 expressed by 35.7, 25, and 17.9% of the
      patients, respectively. This study allows us to determine four pluriepitopic
      regions in Gag and Nef that should be chosen for a vaccine design in a Vietnamese
      population.

PMID- 15989468
TI  - Nevirapine absorbed well despite chronic diarrhea.

PMID- 15989469
TI  - In vitro characterization of a bivalent anti-HER-2 affibody with potential for
      radionuclide-based diagnostics.
AB  - The 185 kDa transmembrane glycoprotein human epidermal growth factor receptor 2
      (HER-2) (p185/neu, c-ErbB-2) is overexpressed in breast and ovarian cancers.
      Overexpression in breast cancer correlates with poor patient prognosis, and
      visualization of HER-2 expression might provide valuable diagnostic information
      influencing patient management. We have previously described the generation of a
      new type of affinity ligand, a 58-amino-acid affibody (Z(HER2:4)) with specific
      binding to HER-2. In order to benefit from avidity effects, we have created a
      bivalent form of the affibody ligand, (Z(HER2:4))2. The monovalent and bivalent
      ligands were compared in various assays. The new bivalent affibody has a
      molecular weight of 15.6 kDa and an apparent affinity (K(D)) against HER-2 of 3
      nM. After radioiodination, using the linker molecule N-succinimidyl p
      (trimethylstannyl) benzoate (SPMB), in vitro binding assays showed specific
      binding to HER-2 overexpressing cells. Internalization of 125I was shown after
      delivery with both the monovalent and the bivalent affibody. The cellular
      retention of 125I was longer after delivery with the bivalent affibody when
      compared to delivery with the monovalent affibody. With approximately the same
      affinity as the monoclonal antibody trastuzumab (Herceptin) but only one tenth of
      the size, this new bivalent molecule is a promising candidate for radionuclide
      based detection of HER-2 expression in tumors. 125I was used in this study as a
      surrogate marker for the diagnostically relevant radioisotopes 123I for single
      photon emission computed tomography (SPECT)/gamma-camera imaging and 124I for
      positron emission tomography (PET).

PMID- 15989470
TI  - Study of monoglutathionyl conjugates TC-99M-sestamibi and TC-99M-tetrofosmin
      transport mediated by the multidrug resistance-associated protein isoform 1 in
      glioma cells.
AB  - The emergence of multidrug resistance (MDR) is a major obstacle to successful
      chemotherapy of malignant glioma tumors. Overexpression of the multidrug
      resistance-associated protein isoform 1 (MRP1), associated with a high level of
      intracellular glutathione (GSH), is a well-characterized mechanism of MDR in
      glioma cells. Previously, we have investigated the role of GSH and MRP1 in the
      accumulation of two radiopharmaceuticals classically used in nuclear medicine:
      (99m)Tc-sestamibi (MIBI) and (99m)Tc-tetrofosmin (TFOS), in a model of glioma
      cell lines. Although the involvement of GSH in MRP1-mediated transport of the two
      radiopharmaceuticals has been demonstrated, the exact transport mechanisms
      involving phase II (conjugation) and phase III (efflux) detoxification of these
      lipophilic cations has not been fully elucidated. To clarify the difference of
      release kinetics observed between MIBI and TFOS, we have studied the efficiency
      of formation of monogluthationyl conjugates mediated by glutathione S-transferses
      (GSTs). Our results clearly demonstrate that, in our model, the main efflux
      mechanism for radiopharmaceuticals is on monoglutathionyl-conjugates of MIBI
      (MIBI-SG) and TFOS (TFOS-SG). These mechanisms involving MRP1, and the phase II
      of detoxification is not efficient for TFOS in resistant glioma cells. A
      relatively slower catalytic efficiency of formation of TFOS-SG conjugate
      (0.006%.s(-1)) prevents its expulsion, contrary to MIBI (0.133%.s(-1)),
      suggesting that TFOS should be interesting in the detection and management of
      patients with high-grade glioma.

PMID- 15989471
TI  - Significant tumor regression induced by microencapsulation of recombinant tumor
      cells secreting fusion protein.
AB  - Implantation of microencapsulated engineered cells secreting molecules with
      antineoplastic properties into tumors is a novel approach to cancer gene therapy.
      In this study, we constructed an engineered tumor cell line, VkCk/RM4-TNF-alpha,
      which secreted RM4/TNF-alpha fusion protein containing the chimeric antitumor
      antibody, F(ab')2 (RM4), recognizing the tumor antigen TAG72, as well as the TNF
      alpha moiety. The engineered cells were encapsulated into microencapsules. The
      RM4/TNF-alpha fusion protein secreted by encapsulated VkCk/RM4-TNF-alpha cells
      could be diffused through the microencapsule membrane into the supernatant and
      exert a cytotoxic effect on L929 cells in vitro. The antigen-specific binding
      reactivity of RM4/TNF-alpha for the TAG72 antigen was confirmed by
      immunohistochemical staining of rat LMCR tumor cells which expressed TAG72
      antigen. Implantation of microencapsules containing VkCk/RM4-TNF-alpha cells into
      LMCR tumors in rats induced tumor regression as a result of tumor necrosis
      formation. Taken together, these data suggest that microencapsulation of
      recombinant tumor cells secreting antibody/cytokine fusion protein might be an
      alternative approach in the treatment of cancers.

PMID- 15989472
TI  - Chemoembolization using cisplatin crystals as neoadjuvant treatment of oral
      cancer.
AB  - Chemoembolization for cancer of the head and neck has been used very rarely in
      the past owing to local characteristics and risks. By combining the
      antineoplastic activity and embolizing effect in the same drug, a more routine
      use seems possible. A cisplatin suspension in normal saline (5 mg in 1 mL) with
      precipitation of microembolizing cisplatin crystals and without additional drugs
      was prepared. The cisplatin dosage was 150 mg/m2, the maximum absolute dose 300
      mg, and the maximum amount of fluid 60 mL. One hundred and three consecutive
      patients with previously untreated squamous cell carcinomas of the oral cavity
      and the anterior oropharynx were treated in a neoadjuvant setting with
      superselective chemoembolization using the cisplatin suspension. Acceptance by
      the patients has been excellent with no refusal. Overall response after one
      intervention has been 73%, with 18.5% showing pathological complete remissions.
      The highest response rates could be seen in T1-3 tumors and tumors of the oral
      tongue and floor of the mouth. Measurable acute systemic toxicity has been low.
      Postembolization syndrome, especially swelling, had to be observed carefully.
      There have been 3.5% interventional and 10% local complications, which could be
      significantly reduced by the use of this procedure only in cancers of the oral
      tongue, floor of the mouth, and mandibular alveolar ridge. Chemoembolization of
      cancer in the head and neck area can be carried out regularly and safely using
      this method, and it is highly effective. It could be used as an induction before
      definitive surgery or radiotherapy. Further investigation is mandatory to assess
      the potential of chemoembolization for the improvement of local control and
      survival.

PMID- 15989473
TI  - Dose-dependent treatment benefit in high-risk melanoma patients receiving
      adjuvant high-dose interferon alfa-2b.
AB  - This retrospective analysis of 150 consecutive high-risk melanoma patients
      treated with high-dose interferon alfa-2b at a single institution demonstrates
      similar relapse-free and overall survival data, as previously published from
      Eastern Cooperative Oncology Group (ECOG) and Intergroup trials. The data suggest
      at least a transient dose dependency of the treatment effect on relapse-free and
      overall survival with high-dose interferon in high-risk melanoma patients.
      BACKGROUND: Adjuvant high-dose interferon seems to be the best adjuvant treatment
      option for patients with high-risk melanoma (AJCC-stage IIC, III) after
      definitive surgery. METHODS: One-hundred fifty consecutive patients were treated
      at our institution during the period from September 1997 to March 2003 were
      retrospectively studied. RESULTS: After a median follow-up of 35 months, 63% of
      patients had developed a melanoma relapse, and 37% were relapse- free. Fifty-five
      percent of patients are still alive, and 45% had died-all but 3 patients from
      melanoma. Patients with stage IIC disease demonstrated a similar unfavorable
      course of disease as patients with stage IIIC disease (2-year relapse-free
      survival 18% and 26%). We identified two groups of patients with different
      cumulative interferon dose-levels (> or =90% and <90% of the projected dose,
      according to the protocol), who demonstrated at least transient differences, both
      in terms of relapse-free and overall survival; the predictive impact was
      statistically independent upon the Cox regression analysis. CONCLUSIONS: Our
      clinical data are consistent with the published ECOG and Intergroup data dealing
      with highdose interferon in high-risk melanoma patients. The data suggest a dose
      dependency on the treatment effect and, therefore, support further prospective
      trials comparing different dose-distribution patterns in high-dose interferon.

PMID- 15989474
TI  - Molecular and immunophenotypical characterization of progressive and regressive
      leukemia cell lines.
AB  - The P815 and P198 cell lines are clonally related mouse mastocytoma cell lines.
      They differ in their biologic behavior in that P815 is a progressive tumor cell
      line, whereas P198 is a regressive one. These cell lines have been extensively
      used as models for the study of tumor-host relationships and tumor immunology.
      Although some of their biological properties have been well documented, the
      molecular mechanisms underlying tumor progression or regression have not been
      completely elucidated. In this study, we characterized the growth behavior and
      immunophenotype of these two cell lines, and analyzed their gene profiles using a
      complementary deoxynucleic acid (cDNA) microarray composed of 514 immunologically
      relevant genes. Our data showed that the two cell lines exhibited quite
      dissimilar and contrasting growth characteristics when inoculated into syngeneic
      mice. P815 tumors grew unremittingly, while P198 tumors gradually regressed. From
      a molecular viewpoint, P815 cells showed a higher expression of genes promoting
      tumor growth, such as IGF-1, IL-8R, FGFR1, VEGF-A, and VEGF-B. On the other hand,
      P198 tumor cells expressed CD11b and CD80, which favor the recruitment of
      lymphocytes and antigen-presenting cells (APCs), as well as the elicitation of
      antitumor immunity. P198 tumor cells also depicted a higher expression of genes
      inhibiting tumor growth, such as TNF-alpha, SOCS-1, CIS1, 4-1BB, and GDF-10. In
      conclusion, our results contribute further information in the understanding of
      the molecular mechanisms associated with the regression and progression of P815
      and P198 tumor cells.

PMID- 15989475
TI  - Radiotherapy of human xenograft NSCLC tumors in nude mice with a 90Y-labeled anti
      tissue factor antibody.
AB  - Tissue factor (TF) is a type I transmembrane protein and the initiator of the
      extrinsic blood coagulation pathway. TF plays a critical role in tumor
      development and its overexpression is observed in many tumors. To understand the
      prevalence and relative level of TF expression in non-small-cell lung cancer
      (NSCLC), we analyzed 50 NSCLC tumors by immunohistochemical staining and found
      that 88% of human NSCLC tumors overexpressed TF. We then generated a high
      affinity anti-TF antibody, TF278, which specifically binds TF on the surface of
      cells and is internalized upon binding. An 111In-labeled TF278 demonstrated
      favorable tumor accumulation in an SW-900 xenograft tumor model with a maximum
      mean percent of injected dose per gram of tissue (%ID/g) of 73.1% at 96 hours
      postinjection. In addition, we labeled the antibody with 90Y and tested its
      ability to inhibit the growth of tumors in an SW-900 xenograft tumor model in
      immunocompromised mice. The 90Y-TF278 slowed the growth of SW-900 tumors at a 50
      microCi dose and completely regressed SW-900 tumors at a 150 microCi dose with
      little toxicity.

PMID- 15989476
TI  - Biodistribution and imaging of FDG in rats with LS174T carcinoma xenografts and
      focal Escherichia coli infection.
AB  - OBJECTIVE: The aim of this study was to compare the dynamic distribution of
      fluorodeoxyglucose (FDG) in malignant and in infectious lesions. METHODS: The
      dynamic distribution of FDG was studied in Rowett nude (RNU) rats with a LS174T
      carcinoma xenograft in the left front leg and an Escherichia coli-induced focal
      infection in the right front leg. In 5 rats, dynamic FDG-PET was performed (27
      frames of 6-15 minutes) up to 4 hours after injection of 11 MBq 18FDG. The mean
      FDG uptake (SUV) was calculated and plotted by using a region of interest (ROI)
      centered over both lesions. In groups of 6 rats, the biodistribution of FDG was
      determined by counting dissected tissues at 1, 2, 3, and 4 hours after an
      injection of 11 MBq FDG. Means +/- the standard error of the mean (SEM) were
      calculated. RESULTS: Dynamic positron emission tomography (PET) visualized both
      the tumor and the infection. The ROI analysis showed that FDG uptake in the
      infections was faster and higher, as compared to the tumor lesions. FDG uptake in
      the tumor reached a standardized uptake value (SUV) of 0.8 +/- 0.3 at 60 minutes
      and in the infectious lesions a SUV of 1.6 +/- 0.2 at 45 minutes, both remaining
      constant until 4 hours postinjection (p.i.). In the biodistribution study with ex
      vivo tissue counting, FDG had accumulated up to 1.1 +/- 0.1 %ID/g and 0.8 +/- 0.1
      %ID/g at 1 hour in the tumor and infection, respectively, and remained constant
      until 4 hours for both lesions without significantly different wash-out from the
      2 lesions. The tumor/blood and abscess/ blood ratios increased with time to 57 +/
      17 and 48 +/- 14, respectively. CONCLUSION: Although in this model differences
      in absolute FDG uptake and initial kinetics between tumor and infection were
      observed, the wash-out rate of FDG from the lesions was similar over time. The
      retention of FDG in the inflammatory lesion indicated that dual time-point
      imaging does not necessarily resolve diagnostic pitfalls for FDG-PET in oncology
      in order to discriminate between malignant tumorous and benign infectious
      lesions.

PMID- 15989478
TI  - Generation of dose-volume histograms using Monte Carlo simulations on a
      multicellular model in radionuclide therapy.
AB  - An accurate calculation of the absorbed dose at the cellular level can lead to
      the optimization of the administered activity and the best clinical response in
      radionuclide therapy. This paper describes the implementation of dose-volume
      histograms (DVHs) for dosimetry at the cellular level in radionuclide therapy.
      The FOTELP code, based on Monte Carlo simulations of photon and electron
      transport, was used on a three-dimensional multicellular tumor model, which
      includes tumor morphometry and cell-labeling parameters. Differential and
      cumulated DVHs were generated for different radionuclides (Cu-67, I-131, Sm-153,
      Y-90, and Re-188) and labeled cell densities (10, 20, 40, 80, and 100%). DVHs
      were generated as a percentage of tumor cells in the function of a relative
      absorbed dose, defined as a cell-absorbed dose divided by an average tumor
      absorbed dose. DVHs for high-energy beta emitters, such as Re-188 and Y- 90, were
      very close to the average tumor-absorbed dose. For low-energy beta emitters, such
      as Cu-67 and I-131, spectra showed that many cells absorbed a much lower dose
      than the average tumor-absorbed dose. Nonhomogeneity of the radionuclide
      distribution in tumor, presented by labeled cell density, had a greater influence
      on DVHs for low-energy beta emitters. Radionuclide therapy plans can be optimized
      using DVHs.

PMID- 15989479
TI  - OEDIPE: a personalized dosimetric tool associating voxel-based models with MCNPX.
AB  - AIM: A new tool, named OEDIPE (a French acronym that stands for "Tool for
      Personalized Internal Dose Assessment") was developed to carry out personalized
      internal dosimetry calculations for nuclear medicine (for both therapeutic and
      diagnostic procedures) and for radiation safety (in the case of internal
      contamination). It was developed under the PV-Wave visual data analysis system by
      the Institute of Radioprotection and Nuclear Safety (IRSN) in collaboration with
      the French Institute of Health and Medical Research (INSERM). This software
      creates anthropomorphic voxel-based phantoms from computed tomography (CT) and
      magnetic resonance imaging (MRI) patient images through the use of a friendly
      graphical user interface (GUI). Several tools have been built-in to allow for
      image segmentation. Source data, including VOI localization and cumulated
      activities, are assessed by single photon emission computed tomography (SPECT)
      images, and the source may be specified in any number of organs either as a point
      source or a homogeneously distributed source. It is also possible to choose the
      dosimetric parameters required for the study (mean organ dose or a dose
      distribution). Phantom, source, and dosimetric parameters are automatically
      written into a file. That file is then processed by the Monte Carlo code MCNPX
      (LANL) to perform the actual dose calculation. RESULTS: OEDIPE can compute either
      the absorbed dose in each organ (in a few minutes), or the absorbed dose in each
      voxel of the phantom (i.e. the spatial dose distribution at a tissue level) in a
      few hours or more. OEDIPE automatically reads the MCNPX output file and processes
      results to give a list of absorbed doses in each organ or a plot of isodose
      curves superimposed onto the phantom. Because of the long calculation times
      required to compute an absorbed dose within an entire whole-body phantom at a
      spatial resolution of a few millimeters, modifications were made to reduce
      computational times to reasonable values. To illustrate this tool, results of a
      dosimetric study of technetium-99m labeling of a bone-scanning agent are
      presented. CONCLUSION: OEDIPE is a tool that can be used for patient-specific
      dosimetry--for example, in targeted radiotherapy--by taking into account the
      individual patient anatomy, including tumors.

PMID- 15989480
TI  - Distribution of radiation in synovectomy of the knee with 166Ho-FHMA using image
      fusion.
AB  - BACKGROUND: Radiation synovectomy is an effective technique for the treatment of
      chronic synovitis in patients with rheumatoid arthritis (RA), and is an
      alternative for surgical synovectomy. Holmium ferric hydroxide macroaggregates
      (166Ho-FHMA) is suitable for radiation synovectomy, especially because it emits
      high-energy beta particles and a smaller proportion of low-energy photons that
      are suitable for gamma-camera imaging. OBJECTIVE: The aim of this study was to
      develop a method to fuse 166Ho-FHMA single photon emission computed tomography
      (SPECT) and magnetic resonance (MRI) images, to show the distribution of 166Ho
      FHMA inside the joint with images that localize synovitis. METHODS: The knees of
      6 patients with RA were treated with 166Ho-FHMA. (99m)Tc-human immunoglobulin
      ((99m)Tc-HIG) SPECT images and MRI images were taken before 166Ho-FHMA
      injections. 166Ho-FHMA SPECT images were taken 4, 28, and 40 hours after
      injections. SPECT and MRI images were merged using a specific image fusion
      method, called mutual information algorithm, to study associations between
      anatomical and metabolic information from these images. RESULTS: Fusion of SPECT
      and MRI images indicated that intensity of radioactivity was associated with the
      amount of synovitis. Activity distribution of 166Ho-FHMA could be registered
      using anatometabolic images. CONCLUSIONS: A new method to fuse the distribution
      of radiation in the synovectomy of the knee was developed using SPECT/MRI image
      registration. Image registration of SPECT and MRI can be used to determine the
      activity distribution of radioisotopes in relation to synovitis.

PMID- 15989481
TI  - Radiosynoviorthesis for treatment of hemophilic hemarthrosis--Slovenian
      experience.
AB  - Radiosynoviorthesis is a well-accepted method for the treatment of recurrent
      hemarthrosis in hemophilic patients. OBJECTIVES: The aims of our study were to
      evaluate the effectiveness of radiosynoviorthesis in patients suffering from
      hemophilic hemarthrosis, to determine the effect of treatment on antihemophilic
      factor consumption, and to assess the patient's satisfaction with
      radiosynoviorthesis. METHODS: Between 2001 and 2003, 26 radiosynoviortheses were
      done in 21 hemophilic patients; in 4 patients the treatment was repeated, and in
      1 patient two joints were treated. 90Y colloid was used for the knee joint, and
      186Re colloid was used for ankle, shoulder, and elbow radiosynoviorthesis.
      RESULTS: The bleeding frequency decreased by at least 50% in 53% of patients in
      the year after radiosynoviorthesis, as compared to the year prior to the therapy.
      Considering only those patients who had at least 12 bleedings into the treated
      joints in the year preceding the therapy, the bleeding frequency decreased by at
      least 50% in 62% of these patients. In this group, the consumption of the
      antihemophilic factor was notably reduced (on average, by 25,800 I.U./year). All
      patients reported that the treated joint was much better or better than before
      the radiosynoviorthesis. CONCLUSION: Radiosynoviorthesis is an effective method
      for the treatment of hemophilic hemarthrosis, particularly in patients with
      frequent intra-articular bleedings. The antihemophilic factor consumption was
      markedly reduced only in patients with frequent joint bleeding.
      Radiosynoviorthesis is well accepted by patients suffering from hemophilic
      hemarthrosis.

PMID- 15989482
TI  - Effects of radiosynovectomy with p-32 colloid therapy in hemophilia and
      rheumatoid arthritis.
AB  - AIM: The aim of this study was to assess the effects of treatment with our
      locally produced P-32 colloidal suspension on knee synovitic inflammations of
      hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results
      with chemical synovectomy or corticoid intra-articular injections and evaluate
      the cost-benefit ratio. MATERIALS AND METHODS: Thirty-six hemophilic male
      patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires,
      Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26
      patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10
      patients). Parents' informed consent was obtained. The following procedures were
      performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus
      monthly methylene diphosphonate (MDP) controls. Patients were included in this
      study only if several knee episodes had occurred. Exclusion criteria included
      bone destruction and big Baker's cyst. Twelve RA patients were included, with
      similar selection criteria: 6 RA patients received P-32 therapy, and the other 6
      patients intra-articular corticoids. Clinical, blind evaluation (state of joint
      involvement, pain, motility, requirements of antihemophilic factors, corticoids,
      or analgesics) was registered in follow-up charts. If required, joint aspiration
      was carried out. Intra-articular instillation of saline plus flushing was done
      before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the
      gamma camera for early and late imaging to confirm the absence of leakage. For
      intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA
      (macroaggregates) was used. Immobilization and relative rest for 72 hours
      followed the procedures. RESULTS: There were neither local or systemic effects,
      nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids
      procedures required frequent injections. Comparison of regions of interest (ROIs)
      in treated knees during soft-tissue scintigraphies in pre- and post-third MDP
      control showed knee improvement. The follow-up evaluation demonstrated an
      increase in joint motion, diminished volume, and less requirement and frequency
      of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21
      of 26), thus lowering health costs. Five female RA patients (5 of 6) had
      decreased joint swelling and pains, resulting in increased joint motion.
      CONCLUSIONS: Radiosynovectomy in RA showed a 3-month pain palliative effect. One
      intra-articular knee radiosynoviorthesis in haemophilic patients provides a more
      than 3- month relief of symptoms after treatment with locally produced P-32 (11
      patients). This turned out to be a safe, economic alternative procedure in
      emerging nations where the availability of AHF is difficult and expensive.

PMID- 15989483
TI  - Radiosynoviorthesis in osteoarthritis and other disorders with concomitant
      synovitis in comparison to rheumatoid arthritis.
AB  - AIM: The aim of this study was to evaluate the effectiveness of
      radiosynoviorthesis (RSO) in osteoarthritis and other disorders with concomitant
      synovitis versus rheumatoid arthritis by means of a standardized questionnaire.
      METHODS: Eight-hundred and three RSO treatments were monitored in 691 patients by
      seven centers in three countries, using standardized questionnaires. Patients
      were assigned to three groups according to their age (20-40, 41-60, and 61-80
      years). Additionally, the data was analyzed separately for patients with
      rheumatoid arthritis (group A) and those with osteoarthritis, psoriasis
      arthritis, pigmental villonodular synovitis, or persistent effusions after joint
      replacement (group B). RESULTS: Quality of life improved in 78% of group A and
      59% of group B (p < 0.01). Ameliorations of joint pain, swelling/effusion, or
      flexibility were found in 80% of group A and 56% of group B (p < 0.01). The
      response rate was similar for small- and large-sized joints in group A, but was
      significantly higher for large-sized joints in group B (p < 0.01). The positive
      effects on joint pain, swelling/effusion, or flexibility lasted longer in group A
      (p < 0.01). Repeated RSOs were as effective as initial RSOs. The clinical outcome
      was not influenced by age, gender, or transient immobilization for 48 hours after
      RSO. CONCLUSION: Although slightly more efficient in rheumatoid arthritis, RSO
      represents an effective treatment option also in osteoarthritis and other
      disorders with concomitant synovitis.

PMID- 15989484
TI  - Reradiosynoviorthesis of the knee.
AB  - The aim of this study was to compare the treatment results between
      radiosynoviorthesis and reradiosynoviorthesis of knees. Before the
      radiosynoviorthesis, an ultrasonography, X-ray, and three-phase bone scintigraphy
      were done. The treatment effect can be expected if a synovitis is proved by these
      examinations. To knees, 200 MBq of the yttrium citrate was injected for the first
      radiosynoviorthesis or for reradiosynoviorthesis. After an application, it is
      possible to do the scintigraphic examination, when information about a tracer
      distribution in joints is obtained. The treatment effect was evaluated by the
      clinical examination, the ultrasonography, and the three-phase bone scintigraphy
      with some lapse of time. If the effect of the radiosynoviorthesis was not
      satisfying, it could be repeated no sooner than 6 months later. Among our
      patients we had a high percentage of the repeated radiosynoviorthesis. The
      authors applicated the yttrium citrate to 1243 knees. A rate between single
      radiosynoviorthesis and reradiosynoviorthesis was 11:8. Repeated
      radiosynoviorthesis were as effective as the initial ones, and their repeated use
      does not decrease the expected therapeutic effect.

PMID- 15989485
TI  - Radiosynovectomy in hemophilic synovitis: correlation of therapeutic response and
      blood-pool changes.
AB  - AIM: The aim of this study was to evaluate the efficacy of 90Y and 186Re
      radiosynovectomy in patients with hemophilic synovitis. METHODS: Radiosynovectomy
      was performed in 32 joints of 20 patients with hemophilic synovitis by using 90Y
      citrate colloid in the knee and 186Re sulfide colloid in the elbow, shoulder, and
      ankle. The indication for radiosynovectomy was the continuous presence of intra
      articular blood or effusion and three or more hemorrhages into the same joint
      within the last 6 months. Response to therapy was first assessed at the 4th month
      with blood-pool imaging. Patients were followed up by clinical evaluation based
      on assessments of joint-bleeding frequency, using range of motion measurements at
      6-month intervals for an average of 1 year (range, 9-15 months). RESULTS: A
      marked decrease (an 80%-100% decrease) in bleeding episodes was seen in 24 of 32
      (75%) joints, a moderate decrease (51%-79% decrease) in 1 (9%) joint, and a mild
      decrease (30%-50%) in 3 (13%) joints. Frequency of intra-articular bleeding after
      treatment was unchanged in only 13% of the joints. The number of hemarthroses
      significantly decreased after therapy (p < 0.05). The mean bleeding frequency of
      the joints were 1.7 +/- 0.9 and 0.3 +/- 0.7 per month before and after therapy,
      respectively. The ratios of joints which had marked improvement after therapy
      were 86% in the ankle, 73% in the elbow, and 58% in the knee. There was no
      significant difference between percent joint range of motion limitations measured
      before and after therapy (p > 0.05). The correlation between therapeutic outcome
      (in terms of joint bleeding) and the difference of pre- and posttherapeutic blood
      pool indices were significant (r = 0.594; p < 0.05), while the correlation
      between therapeutic outcome and pretherapeutic radiologic scale and
      pretherapeutic blood-pool indices were not significant (r = 0.095; p > 0.05; r = 
      0.089; p > 0.05, respectively). CONCLUSION: Radiosynovectomy is a simple but
      quite effective and efficient procedure in limiting the frequency of joint
      hemorrhage in patients with hemophilia. Blood-pool imaging may be an objective
      means for monitoring therapy response in these patients.

PMID- 15989493
TI  - The role of endothelin receptor antagonists in cardiovascular pharmacotherapy.
AB  - Endothelin (ET) is a hormone produced predominantly by endothelial cells which
      has been recognised to play a significant role in the development of several
      cardiovascular disease states. In order to combat the deleterious effects of ET,
      several ET-receptor antagonists (ETRA) are currently in clinical development. The
      agents developed thus far inhibit the actions of ET through either selective
      inhibition of the ET(A) receptors or non-selective inhibition of both ET(A) and
      ET(B) receptors. However, due to the differing proportions of the two receptor
      subtypes in various tissues, animal models and pathologies, it remains a matter
      of debate whether receptor selective agents impart significant clinical benefits
      over non-selective agents. This paper seeks to briefly summarise the important
      preclinical and clinical effects that have been reported in the literature and
      will attempt to provide a rationale for the use of both types of ETRAs in the
      treatment of both systemic and pulmonary hypertension as well as chronic heart
      failure (CHF).

PMID- 15989494
TI  - Emerging therapies for hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) has infected millions of people worldwide and has emerged
      as a global health crisis. The currently available therapy is interferon (IFN)
      either alone or in combination with ribavirin. However, the disappointing
      efficacy of IFN has led to the considerable need for improved treatments and a
      number of new therapies are under evaluation in clinical trials. These include
      pegylated IFNs, which have altered physiochemical characteristics allowing once
      weekly dosing. Combination of pegylated IFN with ribavirin should further improve
      sustained response rates. However, not all patients are successfully treated with
      IFNs, particularly those infected with genotype 1 of the virus, and it is likely
      that potent, specific drugs will be required. The majority of new approaches
      currently trying to combat this viral disease are aimed at inhibition of viral
      targets. Most effort has been directed towards inhibition of the NS3 serine
      protease, and potent inhibitors have now been described. However, a clinical
      candidate is yet to emerge against this difficult target. Considerable work by
      leading researchers has provided crystal structures of the key replicative
      enzymes, NS3 protease, NS3 helicase, NS5B polymerase and full-length NS3 protease
      helicase, and there is much hope that such structural information will bear
      fruit. More recently, inhibition of host targets, particularly inosine
      monophosphate dehydrogenase (IMPDH), has become of interest and there are on
      going clinical trials with such inhibitors. Research aimed at novel treatments
      for HCV disease is gathering pace and very recent developments in cell-based
      assay systems can only hasten the discovery of improved therapies.

PMID- 15989495
TI  - Oxazolidinones: new players in the battle against multi-resistant Gram-positive
      bacteria.
AB  - For many years the pharmaceutical industry did not pursue the development of
      antimicrobial agents that specifically targeted Gram-positive bacteria. Semi
      synthetic penicillins and vancomycin were the mainstays of therapy for
      methicillin-susceptible and -resistant strains of staphylococci, respectively, as
      was penicillin for Streptococcus pneumoniae and beta-lactam-aminoglycoside
      combinations for serious enterococcal infections. In the 1980s enterococci
      resistant to glycopeptides emerged, followed shortly thereafter by a
      dissemination of penicillin-insensitive S. pneumoniae and, more recently, the
      occurrence of vancomycin-intermediately susceptible Staphylococcus aureus. The
      emergence of fully glycopeptide-resistant S. aureus is clearly on the horizon.
      Multi-resistant Gram-positive bacteria now pose an important therapeutic
      challenge for clinicians. New drugs with activity against some of these dangerous
      pathogens have recently been pursued, and linezolid, the first member of the
      oxazolidinone class, has now been licensed for clinical use in many countries.
      This drug has excellent in vitro and in vivo activity against all clinically
      relevant multi-resistant Gram-positive cocci and fills an important void in
      infectious disease chemotherapy.

PMID- 15989496
TI  - Serotonergic modulation and irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a debilitating disease, which is characterised
      by recurrent abdominal cramping and pain, and is associated with either
      constipation and/or diarrhoea. It is approximately twice as prevalent in women as
      it is in men and is among the most common gastrointestinal (GI) disorders
      encountered in primary care. The aetiology of the disease is poorly understood
      but may include motility dysregulation, visceral sensitivity, inflammation,
      bacterial infection, dietary antigens, psychological stress, GI surgery or a gut
      brain phenomenon. At present, there is no acceptable treatment for IBS, although
      recent advances indicate that some relief may be achieved by the administration
      of compounds that act on 5-HT (serotonin) receptors. This suggestion is the
      result of numerous studies which have shown that 5-HT may exert a number of
      diverse effects on human GI tissues. In addition, it has emerged that the levels
      of the 5-HT metabolite (5-HIAA) are raised in the plasma of IBS patients and that
      administration of 5-HT-like compounds may mimic the symptoms of IBS. It has
      therefore been proposed that therapy with compounds that act at 5-HT receptors
      will return the intestine to normal activity and alleviate the pain experienced
      by these patients. One compound (alosetron, a 5-HT3 receptor antagonist) has
      already been released onto the market but showed benefit in female patients only
      and only in those whose primary symptom was diarrhoea. In addition, the compound
      was recently withdrawn following concerns over its safety. The reasons why
      alosetron only appears to show efficacy in females, why these treatments are only
      effective in a subset of the population of IBS patients and why alosetron elicits
      its particular side effect profile have not been elucidated. One further
      serotonergic compound, tegaserod (Zelmac, a 5-HT4 receptor agonist), has shown
      promise for the treatment of patients with constipation-predominant IBS and is
      currently in pre-registration for this indication. It is clear, however, that
      further research will have to take place before the utility of serotonergic
      modulation in the treatment of IBS can be fully validated.

PMID- 15989497
TI  - Clinical trials of a new class of therapeutic agents: antisense oligonucleotides.
AB  - Antisense oligodeoxynucleotides (ODNs) are short stretches of DNA complementary
      to a target mRNA. The ODNs selectively hybridise to their complementary RNA by
      Watson-Crick base pairing rules. In theory, the use of antisense ODNs provides a
      method to specifically inhibit the intracellular expression of any disorder whose
      genetic aetiology is well known. For this reason, researchers thought that if
      antisense drugs proved to be so specific there would be no side effects. However,
      toxicity-related problems arose in initial animal studies of antisense drugs in
      the early 1990s and since then companies have been using these compounds
      cautiously. In order to be useful therapeutically, an ODN must (a) exhibit
      reasonable stability in the physiological environment, (b) be taken up and
      retained in adequate quantities by the target cells, (c) specifically bind target
      mRNA with high affinity, (d) have an acceptable therapeutic ratio, free of
      unwanted toxic and non-specific side effects and (e) be easily synthesised in
      sufficient quantities to allow clinical use. Most of these criteria have already
      been met by ODNs recently used in this way. This review describes certain
      therapeutic applications of antisense techniques currently under investigation in
      oncology, haematopathology and inflammatory diseases.

PMID- 15989498
TI  - Caspase inhibitors as neuroprotective agents.
AB  - Apoptotic neuronal cell death has been demonstrated to occur in the central
      nervous system (CNS), following both acute injury and during chronic
      neurodegenerative conditions. Currently, the majority of experimental evidence
      for a role of caspases in CNS damage has been established following acute
      neuronal insults, including ischaemic stroke, traumatic brain injury and spinal
      cord injury. In vitro and in vivo models have been used to demonstrate caspase
      activation, and treatment with available caspase inhibitors can provide
      significant protection. Overall, acute neuronal injury represents a major unmet
      medical need and caspase inhibitors may be an attractive approach to preserve
      neuronal function by extending the therapeutic window and providing long-term
      neuroprotection. Currently, several inhibitors are in preclinical drug
      development and this review summarises recent advances in the development of
      novel caspase inhibitors for the treatment of acute neuronal injury.

PMID- 15989499
TI  - The effect of HMG-CoA reductase inhibitors on chronic allograft rejection.
AB  - Hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have
      pleiotropic actions that affect many systems other than lowering blood
      cholesterol concentrations. Hypercholesterolaemia is an adverse effect of
      immunosuppressive drug therapy and hence it is a common finding after organ
      transplantation. HMG-CoA reductase inhibitors lower cholesterol concentrations in
      transplant recipients but they also offer additional benefits. Since they impair
      the production of mevalonate, they reduce the concentrations of downstream
      products including farnesyl and geranyl phosphate. These isoprenoid moieties are
      required for protein prenylation and HMG-CoA reductase inhibitors impair this
      function in some cells. This action affects the immune system, especially in
      patients taking cyclosporin, and has been proposed as the mechanism whereby these
      drugs increase the half-life of transplanted organs. Other mechanisms have also
      been proposed including an increase in the free fraction of cyclosporin and a
      reduction in the time that low density lipoprotein (LDL) spends in blood. The
      latter effect reduces the extent of oxidation of LDL and hence reduces the damage
      caused by oxidised LDL. Chronic rejection is poorly understood but appears to
      involve both immune and non-immune processes. HMG-CoA reductase inhibitors affect
      both processes. At present, the evidence of benefit from statin prescription is
      confined to heart and kidney transplant recipients but it is likely that
      recipients of other organ transplants would also benefit. Drug interactions
      between cyclosporin and HMG-CoA reductase inhibitors are a limiting factor to
      their use. Pravastatin appears to be the best HMG-CoA reductase inhibitor for
      organ transplant recipients because of its lesser potential to interact with
      cyclosporin and hence cause myositis, which may thus allow higher doses to be
      used. Other, non-immunosuppressive drugs (including diltiazem and ketoconazole)
      have been shown to reduce transplant organ damage by unknown mechanisms and are
      widely prescribed in some transplant centres. More specific inhibitors of protein
      prenylation may afford useful immunosuppression, thereby prolonging transplant
      organ half-lives and also reducing the risk of cancer.

PMID- 15989500
TI  - Emerging anticoagulant and thrombolytic drugs.
AB  - Since its discovery, heparin has been used intensely as an anticoagulant for
      several medical and surgical indications. However, efforts are in progress to
      replace heparin because of its serious complications, such as intraoperative and
      postoperative bleeding, osteoporosis, alopecia, heparin resistance, heparin
      rebound, heparin-induced thrombocytopenia (HIT) and thrombosis syndrome (HITTS),
      and other disadvantages. Significant developments in the field of new
      anticoagulants have resulted in the evaluation and introduction of low molecular
      weight heparins (LMWHs) and heparinoids, hirudin, ancrod, synthetic peptides and
      peptidomimetics. However, despite significant progress in the development of
      these new anticoagulants, a better or an ideal anticoagulant for cardiovascular
      patients is not yet available and heparin still continues to amaze both basic
      scientists and the clinicians. To minimise the adverse effects of heparin, newer
      approaches to optimise its use in combination with the new anticoagulants may
      provide better clinical outcome. In our experience, the off-label use of
      argatroban at a dose of 300 microg/kg iv. bolus followed by 10 microg/kg/minute
      infusion in combination with aggrastat (a glycoprotein [GP] IIb/IIIa inhibitor)
      at a dose of 10 microg/kg iv. bolus followed by an infusion of 0.15
      microg/kg/minute in patients with HIT undergoing percutaneous coronary
      interventions resulted in elevation of celite activated clotting time (ACT) to
      300 seconds followed by a gradual decline and the ACT remained above 200 seconds
      even after 200 min of drug administration. A bewildering array of newer
      anticoagulants now exist, such as LMWHs and heparinoids, indirect or direct
      thrombin inhibitors, oral thrombin inhibitors, such as melagatran (AstraZeneca)
      and HC-977 (Mitsubishi Pharmaceuticals), Factor IXa inhibitors, indirect or
      direct Factor Xa inhibitors, Factor VIIa/tissue factor (TF) pathway inhibitor,
      newer antiplatelet agents, such as GPIIb/IIIa inhibitors, fibrin specific
      thrombolytic agent, such as tenecteplase and modulation of the endogenous
      fibrinolytic activity by thrombin activatable fibrinolytic inhibitor (TAFI),
      Factor XIIIa inhibitors and PAI-1 inhibitors. The quest for newer anticoagulant,
      antiplatelet and fibrinolytic agents will continue until ideal agents are found.

PMID- 15989501
TI  - Therapeutic potential of oestrogen receptor ligands in development for
      osteoporosis.
AB  - Accelerated bone loss secondary to loss of ovarian function at menopause is well
      recognised as a major risk factor for osteoporotic fractures in postmenopausal
      women. Postmenopausal bone loss can be prevented or arrested by oestrogen
      replacement therapy (ERT). It has also been reported that ERT protects against
      cardiovascular disease by improving the serum lipid profile, however there are
      mixed reports concerning these benefits. Unopposed ERT causes an unacceptable
      increase in the risk of endometrial cancer and proliferative effects in mammary
      tissue resulting in an increased risk of breast cancer. While this can be
      counteracted by combining ERT with a low-dose of a progestin, withdrawal bleeding
      and the continuing uncertainty about the effect of oestrogen on the risk of
      breast cancer contribute to poor compliance for long-term use. Because of the
      known and suspected risks of oestrogen therapy it has been estimated that in the
      US < 40% of women on ERT will continue treatment beyond one year. An ideal
      therapy would retain the desirable skeletal and cardiovascular effects of
      oestrogen, lack oestrogenic activity on the endometrium and reduce the incidence
      of breast cancer. The concept of selective oestrogen receptor modulation (SERM)
      has been demonstrated for a number of compounds including tamoxifen, raloxifene,
      droloxifene, GW-5638 and levormeloxifene. However, the clinical utility of these
      agents will depend on the profile of tissue-specific effects and the extent to
      which they are translated into in vivo efficacy. A SERM is defined as a compound
      that has oestrogen agonism on one or more of the desired target tissues, such as
      bone or liver, and has antagonism and/or minimal agonism (i.e., clinically
      insignificant) in reproductive tissue, such as the breast or uterus. Although
      tamoxifen acts as a SERM, it is also associated with an increased incidence (4%
      gynaecological symptoms greater than placebo control) of endometrial cancer.
      Indeed, there have been a number of mechanistic-based studies to explain the
      increased incidence of endometrial carcinomas in tamoxifen treated patients,
      which provide an in vitro insight into the adverse clinical observations in vivo.
      Attempts to improve on the pharmacological profile of tamoxifen have resulted in
      compounds that differ in their oestrogen agonist/antagonist characteristics,
      including the pure oestrogen antagonists. This suggests that it may be possible
      to develop a molecule with a desired profile of tissue-specific
      agonist/antagonist activities by establishing bone and cardiovascular protective
      effects but having no effects (or even behaving as an antagonist) in the
      reproductive tissues.

PMID- 15989502
TI  - Tumour angiogenesis: a novel therapeutic target in patients with malignant
      disease.
AB  - Angiogenesis refers to the formation of new blood vessels from an existing
      vasculature and is recognised as a necessary requirement for most tumours to grow
      beyond 1-2 mm in diameter. Factors established as playing a role in angiogenesis
      may be divided into two principal groups: (a) those that stimulate endothelial
      cell proliferation and/or elongation, migration and vascular morphogenesis
      including vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), platelet derived endothelial cell growth factor (PD-ECGF) and the
      tie and tek receptors, and (b) proteases and their receptors involved in the
      breakdown of basement membranes and the extracellular matrix (ECM) including the
      matrix metalloproteinases (MMPs), cathepsins and those involved in the plasmin
      cascade. Angiogenesis has been identified as a potential target for development
      of anticancer agents. The discovery of a range of naturally-occurring factors
      which negatively regulate angiogenesis, including the thrombospondins,
      angiostatin and endostatin, and the tissue inhibitors of MMPs (TIMPs), has given
      added impetus to this approach. Synthetic anti-angiogenic compounds have been
      developed, including TNP-470, carboxyamidotriazole, VEGF-tyrosine kinase
      inhibitors and MMP inhibitors (MMPI) which, like the naturally-occurring anti
      angiogenic factors, inhibit angiogenesis in vitro and in vivo, and tumour
      development, growth and metastasis in vivo. Anti-angiogenic agents also enhance
      the antitumour activity of many conventional cytotoxic chemotherapeutic agents.
      Such combinations may have a particular role as adjuvant therapies following
      surgical resection of primary tumours. Unlike tumour cells, tumour associated
      endothelial cells do not develop resistance to anti-angiogenic agents.
      Furthermore, anti-angiogenic agents are generally cytostatic rather than
      cytotoxic. As such, these agents are, in general, likely to be administered over
      long periods of time. Therefore, as well as having proven antitumour efficacy, an
      anti-angiogenic compound will need to be well-tolerated if it is to become
      established in the clinical management of patients with malignant disease.

PMID- 15989503
TI  - GABAB receptor agonists and antagonists: pharmacological properties and
      therapeutic possibilities.
AB  - Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, is widely
      distributed throughout the brain and spinal cord. Two major families of GABA
      receptors have been identified, GABAA and GABAB. While much is known about the
      pharmacological and molecular properties of GABAA receptors, it is only within
      the last few years that potent and selective antagonists have been developed for
      the GABAB site, and only within the past few months that this receptor has been
      cloned. Thus, tools are now available to define more fully the GABAB receptor in
      terms of its biology and the therapeutic potential of manipulating this site.
      Data suggest that, in addition to their established use as muscle relaxants,
      GABAB receptor agonists possess analgesic and antitussive properties, and may be
      useful for treating bladder dysfunction. While there is less clinical data on
      GABAB receptor antagonists, preclinical results indicate that they may be of
      value in treating absence epilepsy, cognitive dysfunction and, possibly,
      pulmonary and intestinal disorders. However, for this potential to be fully
      exploited, it is necessary to identify and characterise molecularly and
      pharmacologically distinct GABAB receptor subtypes.

PMID- 15989504
TI  - Vagus nerve stimulation: current status and clinical applications.
AB  - Despite the recent introduction of new anti-epileptic drugs (AEDs), many patients
      with epilepsy, especially those with partial-onset seizures, continue to have
      seizures that are refractory to pharmacotherapy. Other patients are unable to
      tolerate the side-effects of AEDs given singly or in combination. Cerebral
      resective surgery may be an option for a sub-group of these patients; however,
      many patients with refractory partial epilepsy are not optimal candidates for
      epilepsy surgery. Consequently, the introduction of left vagus nerve stimulation
      (VNS) for those patients who have been afflicted by seizures or medication side
      effects has opened up a new, non-pharmacological approach to epilepsy treatment.
      The mechanism of action of VNS is uncertain. VNS exerts an anticonvulsant effect
      in a variety of animal seizure models; has no effect on hepatic metabolic
      processes, serum concentrations of AEDS, or laboratory values; and has no
      clinically significant effect on vagally-mediated physiological processes. VNS is
      safe and well-tolerated in patients with long-standing, medically-refractory,
      partial-onset epilepsy. Adverse effects are usually mild to moderate in severity
      and related to stimulation, and almost always resolve with adjustment in
      stimulation settings. Controlled studies of patients on AED therapy show that
      adjunctive VNS is effective for partial-onset seizures when given every 5 min for
      30 s intervals. Results of studies in paediatric patients are encouraging.

PMID- 15989505
TI  - Emerging applications of hormonal therapy of paroxysmal central nervous system
      disorders.
AB  - Gonadal and adrenal steroidal hormones and their related neuropeptides affect
      seizures. Seizures, in their turn, may affect the functioning of these endocrine
      systems. Both these sets of effects may be clinically important and open to
      therapeutic manipulation. Recent advances in understanding the effects of these
      hormones and their metabolites on neuronal excitability have opened the way for a
      number of new, hormonally-based therapeutic approaches to seizure management.
      Some of these have reached various stages of clinical trials, while others are
      still in the preclinical stages of testing. Similarly, treatment of some of the
      hormonal consequences of seizures has recently been explored and will be
      discussed.

PMID- 15989506
TI  - Novel developments with selective, non-peptidic kappa-opioid receptor agonists.
AB  - Despite the recent introduction of a number of new compounds, there has of late
      been a cooling of interest by pharmaceutical companies in the development of
      centrally-active, selective kappa opioid agonists for therapeutic purposes. This
      is reflected in the discontinuation of a number of clinical trials, for reasons
      that are often not completely clear to outside observers. Spiradoline and
      enadoline have apparently been abandoned as potential analgesics because they
      induce dose-limiting central side-effects (i.e., dysphoria) in models of post
      surgical pain. The development of niravoline as an aquaretic for the treatment of
      cirrhosis with ascites and other hyponatraemic disorders has also been halted.
      Enadoline may yet find some application against ischaemic stroke and severe head
      injury, presumably in comatose patients in whom psychiatric side-effects are
      taken to be immaterial, while apadoline and TRK 820 remain in Phase II clinical
      testing against cancer pain. The peripherally-selective kappa agonists,
      asimadoline, and the atypical compound, fedotozine, are well-tolerated in man.
      Results of Phase III trials of fedotozine against irritable bowel syndrome and
      dyspepsia have, however, ultimately been disappointing, whereas asimadoline is
      currently in Phase II clinical trials against pain of rheumatic and
      osteoarthritic origin. The results of these trials are eagerly awaited.

PMID- 15989507
TI  - Animal models with potential applications for screening compounds for the
      treatment of obsessive-compulsive disorder.
AB  - The availability of an animal model for obsessive-compulsive disorder (OCD) is
      necessary for the development of novel pharmacological treatments. To be useful,
      the model must be predictive of clinical performance, possess characteristic
      criteria and distinguish anti-OCD from antidepressant compounds. Due to the lack
      of OCD models useful for drug discovery, all compounds currently used for OCD
      were developed first as antidepressants. In this article, we discuss the relative
      merits of: stereotypic behaviours (canine acral lick, feather picking,
      amphetamine- and 5-HT-induced stereotypy); adjunctive and displacement behaviours
      (schedule-induced polydipsia, wheel running, resident-intruder grooming);
      anxiolytic tests (separation and shock-induced ultrasonic vocalisation and marble
      burying); and depression tests (inescapable shock-induced escape and immobility
      in forced swim) as potential OCD models. We conclude that adjunctive and
      displacement behaviours, and in particular schedule-induced polydipsia, may prove
      to be the best models for compulsive behaviour in animals that can be used for
      the discovery of novel anti-OCD agents.

PMID- 15989508
TI  - The therapeutic use of botulinum toxin.
AB  - Since Alan Scott's research, botulinum toxin (BoNT) has been used in several
      diseases or conditions characterised by muscular overactivity. BoNT acts on
      either neuromuscular or autonomic cholinergic junctions. Seven different
      serotypes are known, with antigenic specificity and different therapeutic
      profiles. BoNT is made up of a heavy chain, involved in binding and membrane
      translocation, and a light chain, involved in blocking neuroexcytosis. Each
      serotype shares a specific acceptor on the presynaptic membrane of a cholinergic
      junction. The available BoNT preparations differ in toxicity, purity and
      stability. Injection of the neurotoxin produces several modifications at a
      neuromuscular junction. Axonal sprouting, muscular fibre atrophy, and new end
      plates are the most evident histological events after BoNT treatment. They appear
      to be reversible in untreated muscles. Diffusion can occur at first by
      haematogeneous or local BoNT spread. Several factors, such as dose, volume, site
      of injection, muscle size, and muscular fascia, can influence the amount of
      diffusion and possible side-effects. After prolonged BoNT treatment patients can
      become unresponsive. Antibodies directed against BoNT have been observed with
      ELISA or mouse bioassay. Different serotypes have been used to treat non
      responder patients. Novel toxins with lower immunogenicity and prolonged clinical
      efficacy are required for more effective treatment.

PMID- 15989509
TI  - Muscarinic agonists for the treatment of Alzheimer's disease: progress and
      perspectives.
AB  - Much interest has focused on the development of selective muscarinic agonists for
      the treatment of Alzheimer's disease (AD). Cholinergic replacement therapy is
      thought to be beneficial in alleviating some of the cognitive dysfunctions in
      this disorder. The cholinergic neuronal tracts are involved in memory and
      learning processes, and the extent of the degeneration of the cortical
      projections correlates with the severity of the dementia. An M1 selective
      muscarinic agonist may be effective in treating at least some of the cognitive
      symptoms in AD. Highly selective M1 agonists, producing cellular excitation,
      should be beneficial in AD, regardless of the extent of degeneration of
      presynaptic cholinergic projections to the frontal cortex or hippocampus.
      Functional abnormalities in AD may also occur along various signal transduction
      pathways mediated, in part, at least, by muscarinic receptors. In general,
      activities associated with mAChR subtypes and m1 receptors, in particular,
      indicate that M1 agonists may also be useful for this aspect of AD. Mismetabolism
      of amyloid precursor proteins (APPs) may induce AD. Recent studies indicate that
      the formation of the b-amyloid peptide (Abeta) and amyloid plaques is linked to
      the loss of cholinergic function in AD. New data on the activation of m1 mAChRs
      in conjunction with recent findings that the induction of such receptors
      stimulates neurotrophic-like activities, decreases tau phosphorylation and
      inhibits apoptosis indicate that restoring the cholinergic tone in AD may be
      useful both in improving memory function and in altering the onset and
      progression of AD dementia. This article focuses on the recent, promising
      developments in this field and assesses the value of muscarinic agonists
      currently under development for the treatment of AD.

PMID- 15989510
TI  - AIT-082, a novel purine derivative with neuroregenerative properties.
AB  - Preclinical and clinical evidence support the effectiveness of neurotrophins in
      Alzheimer's disease (AD) and neurodegenerative diseases. Delivery of
      neurotrophins to target sites in the brain remains a major obstacle for their use
      in humans. Development of orally active agents that mimic the effects of nerve
      growth factor and other neurotrophins provides a promising alternative
      therapeutic strategy. AIT-082, a purine analogue, has been shown to reverse age
      induced memory deficits in mice and is a growth factor-mimetic agent. It is
      orally active, rapidly penetrates the blood-brain barrier and induces the
      production of multiple growth factors at the appropriate target site in the
      central nervous system (CNS).

PMID- 15989511
TI  - Adenoviral vectors: development and application.
AB  - One of the prerequisites for the successful application of gene vaccination and
      therapy is the development of efficient gene delivery vectors. The rate-limiting
      nature of vectors was clearly manifested during the first wave of gene therapy
      testing, resulting in the demand for more effective and suitable vector systems.
      Adenoviral (Ad) vectors have recently played a central role in the development of
      gene-vector technology due to their practical advantages and potential
      applications. A large number of preclinical and clinical studies both have
      generated an overwhelming amount of data and literature on this vector system. It
      is the intention of this article to provide a systematic and broad spectrum
      review of this system, outlining the principle, potential, and limitations, and
      evaluating the rational development of this delivery approach. Recombinant
      adenoviruses (Ad), helper cell lines, and related technologies have been
      developed and applied to many indications owing to progress in virological
      research, molecular and cellular biology, eukaryotic protein expression,
      recombinant vaccines, and gene therapy. The technical depth this article covers
      should be useful to both the experienced researcher and to beginners in this
      field.

PMID- 15989512
TI  - Towards a gene therapy for cystic fibrosis lung disease.
AB  - Gene therapy for the treatment of the pulmonary manifestations of cystic fibrosis
      (CF) has been at the forefront of gene therapy research over the last several
      years. During this time, however, despite immense efforts, controlled clinical
      trials with CF patients have failed to demonstrate significant and reproducible
      ;correction' of the CF bioelectrical functional defect. The target tissue
      requiring ;correction' in CF lung disease is the respiratory epithelium that
      lines the airways of the lung, and evidence is now emerging that the epithelium
      has evolved to elude the uptake of potential pathogens, including viruses,
      bacteria and gene transfer vectors. The majority of studies with gene transfer to
      the airway epithelium have used the adenovirus as the gene delivery vector, since
      high efficiency gene transfer to airway epithelial cells grown in culture can be
      demonstrated. However, when these vectors are tested in the airways of animals
      and humans in vivo, the efficiency of gene transfer is low. It is likely that
      these observations are not limited to adenoviral vectors (Ad), since similar gene
      transfer discrepancies are observed with a range of vector systems being
      developed for CF lung gene therapy. Therefore, this update will focus on the
      factors responsible for efficient gene transfer to airway epithelial cells in
      vitro and, using Ad as examples, discuss the development of ;targeted' gene
      transfer vectors that may overcome the resistance of the airway epithelium in
      vivo to efficient gene transfer.

PMID- 15989513
TI  - Adhesion molecules: opportunities for modulation and a paradigm for novel
      therapeutic approaches in cancer.
AB  - In the past decade, there have been major advances in the elucidation of
      processes underlying tumour invasion and metastasis, in which adhesion molecules
      play a critical role. These advances have revolutionised our ability to devise
      novel approaches for cancer treatment. This review gives an insight into the
      adhesion pathways, and highlights the current status of adhesion molecules as
      potential therapeutic targets.

PMID- 15989514
TI  - Dual beta-lactam-fluoroquinolone compounds: a novel approach to antibacterial
      treatment.
AB  - Codrugs comprise a beta-lactam-fluoroquinolone antibacterial hybrid. These new
      agents have been developed with the aim of enhancing the antibacterial spectrum
      of current therapies, overcoming intrinsic and acquired resistance, and
      diminishing severe side-effects. A few compounds, including Ro 23-9424, have
      entered Phase I clinical trials. Furthermore, a series of oral codrugs have been
      synthesised, although clear oral bioavailability has not yet been demonstrated.
      New drugs are urgently needed to treat Gram-positive resistant bacteria.

PMID- 15989515
TI  - Sialidase as a target for inhibitors of influenza virus replication.
AB  - Structure-based drug design has led to the identification of potent and selective
      inhibitors of influenza virus sialidase, which have antiviral activity in vitro
      and in experimental animal models of influenza infection. Clinical studies with
      one such sialidase inhibitor, zanamivir, have shown this compound to be a safe
      and effective therapy for influenza infections in man. Passage of influenza
      viruses in the presence of zanamivir in vitro has been shown to result in the
      selection of viruses with reduced sensitivity to this drug. To date, however,
      there have been no reports of the isolation of zanamivir-resistant viruses during
      clinical studies of this compound. Further application of structure-based drug
      design is yielding novel classes of potent inhibitors of influenza virus
      sialidase.

PMID- 15989516
TI  - Head injury therapies.
AB  - The results of clinical trials in traumatic brain injury have to date been
      disappointing, despite promising results with animal models. Some of the agents
      which have been tested in clinical trials and some which are currently under
      evaluation are reviewed, and possible reasons for the lack of clinical benefit
      are discussed.

PMID- 15989517
TI  - Donepezil (E2020): a new acetylcholinesterase inhibitor. Review of its
      pharmacology, pharmacokinetics, and utility in the treatment of Alzheimer's
      disease.
AB  - Donepezil is an acetylcholinesterase inhibitor under development for the
      treatment of mild-moderately Alzheimer's disease. In vitro, donepezil is about 10
      times more potent than tacrine as an inhibitor of acetylcholinesterase. Donepezil
      is 500 - 1000 fold selective for acetylcholinesterase over butyrylcholinesterase.
      In animal models, donepezil produces positive effects on both working memory and
      long term memory. In man, donepezil is slowly absorbed from the gastrointestinal
      (GI) tract. The compound has a terminal elimination half-life of 50 - 70 h in
      young volunteers; in elderly volunteers, the half-life of the compound is
      extended to over 100 h. Donepezil is extensively metabolised after oral
      administration. The parent compound is 93% bound to plasma proteins. Results from
      two clinical trials with donepezil were published. The largest of these trials
      was a 12 week 161 patient Phase II investigation in the USA. Results from this
      investigation showed that donepezil produced dose-related improvements, with
      statistically significant effects occurring at doses of 3 and 5 mg/day. The
      results published to date suggest that donepezil will be a useful agent in the
      symptomatic treatment of Alzheimer's disease.

PMID- 15989518
TI  - Tazarotene: a review of its pharmacological profile and potential for clinical
      use in psoriasis.
AB  - Psoriasis appears to be a T-cell-mediated, HLA-associated genetic skin disease
      that profoundly alters epidermal differentiation in a reversible manner. The
      topical treatment of mild-to-moderate stable plaque psoriasis is limited by side
      effects, cosmetic problems, and often by unsatisfactory efficacy, while systemic
      therapy is usually not warranted because of safety concerns. Tazarotene is the
      first member of a novel acetylenic and non-isomerisable class of retinoids to
      undergo extensive clinical testing. Tazarotene therapy regulates gene
      transcription via interaction with specific nuclear retinoic acid receptors
      (RARs), thereby modulating the three key pathogenic factors in psoriasis.
      Systemic absorption is minimal and, in contrast to some other retinoids,
      elimination is rapid. The results of Phase II and Phase III controlled clinical
      studies have shown tazarotene to be an effective treatment for psoriasis. The
      clinical response is rapid, and in many patients was sustained for several weeks
      following discontinuation of therapy. Adverse effects are generally limited to
      mild-to-moderate local effects, as seen with other topical retinoid therapies.
      Convenient once-daily application of tazarotene gel is effective first-line
      monotherapy for mild-to-moderate plaque psoriasis, providing rapid and sustained
      benefits, while minimal systemic absorption and rapid elimination appear to limit
      the potential for systemic side-effects.

PMID- 15989519
TI  - The 134th British Pharmaceutical Conference.
AB  - The 134th British Pharmaceutical Conference was held at Scarborough from 15th -
      18th September 1997. Among a wide variety of topics, proffered papers and posters
      were two symposia on aspects of drug design.

PMID- 15989520
TI  - Prospects and problems of gene therapy: an update.
AB  - The gene therapy approach can vary from delivering extra copies of a gene,
      through modifications of a genome using the properties of ribozymes or
      chimeraplasts, to injection of modified cells. For the treatment of genetic
      deficits the ultimate goal would be the repair of the mutated gene in the target
      tissue(s). The techniques required for such an approach are emerging, albeit
      slowly. Therefore, delivery of an extra copy of a normal gene in a specific
      vector remains the predominant approach. Moreover, this method finds wider
      applications in gene therapy relating to disorders other than heritable defects,
      e.g., malignancies, cardiovascular diseases and infections. The major and most
      intensive areas of research are: i) vectors and delivery methods, ii) regulation
      of transgene expression and iii) stability of expression. Targeting of the
      therapeutic gene is being accomplished by using viral vectors or non-viral
      delivery systems, either ex vivo or in vivo. The choice of vectors and delivery
      routes depends on the nature of the target cells and the required levels and
      stability of expression. Although there have been the first positive clinical
      results and significant technical achievements over the past 2 years, there are
      still obstacles to the development of effective clinical products and these
      remain largely unchanged. The most important barriers are the low levels and
      stability of expression and immune responses to vectors and/or gene products. The
      safety aspects of gene therapy have become painfully evident with the first death
      conclusively linked to gene therapy. The progress in AAV and lentiviral vectors,
      improved regulation of transgene expression and advances in stem cell technology
      are among the recent most exciting developments.

PMID- 15989521
TI  - Emerging therapies for human papillomavirus infection.
AB  - Human papillomavirus (HPV) is the most common sexually transmitted infection,
      with > 50% of sexually active women being affected. The virus causes a wide
      variety of benign and pre-malignant epithelial tumours and although most
      infections are transient, it is estimated that 1% of the sexually active
      population in the US have clinically apparent genital warts. A subset of genital
      HPVs, termed high-risk HPVs, is highly associated with the development of genital
      cancers including cervical carcinoma. Therapies for these HPV related cancers are
      however outside of the scope of this review. The absence of a simple monolayer
      cell culture system for analysis and propagation of the virus has substantially
      retarded progress in the development of diagnostic and therapeutic strategies for
      HPV infection. In spite of these difficulties, great progress has been made in
      the elucidation of the molecular controls of virus gene expression, replication
      and pathogenesis, and there has been some progress in the development of
      prophylactic and therapeutic vaccines and of other therapies.

PMID- 15989522
TI  - Fusion/entry inhibitors as therapies for HIV.
AB  - A combination of three or more antiretroviral drugs, commonly termed 'highly
      active antiretroviral therapy' (HAART), has become the standard-of-care treatment
      for HIV-related disease in the developed world. Since its initiation in the mid
      1990s, HAART has led to substantial reductions in both mortality and morbidity.
      There are, however, significant problems associated with existing therapies
      including high pill burdens and serious side effects in many patients, as well as
      the emergence and transmission of drug-resistant HIV variants. There is,
      therefore, a need for new medicines to treat HIV infections, both from the
      existing drug classes and, perhaps more importantly, a need for medicines that
      act against the virus in entirely new ways. In recent years, much has been
      learned about how HIV enters its target cells and this work has led to the
      identification of compounds that potently inhibit the individual steps of viral
      entry. The status of current research focussed on preventing HIV entry is
      described below.

PMID- 15989523
TI  - Antiviral activity of 4-benzyl pyridinone derivatives as HIV-1 reverse
      transcriptase inhibitors.
AB  - In this overview, the antiviral properties of the Curie-pyridinone compounds, a
      new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) developed
      as anti-HIV agents, are described. These compounds are hybrids between
      hydroxyethoxymethyl-phenylthiothymine (HEPT) and Merck pyridinones. Several
      structure-activity relationships (SAR) studies between HIV-1 reverse
      transcriptase (RT) and the Curie-pyridinones are described. The Curie-pyridinones
      are potent inhibitors of both HIV-1 replication in cell culture and of HIV-1 RT
      activity in vitro. They are specific to HIV-1 and do not inhibit the replication
      of HIV-2. The mechanism of inhibition is non-competitive with respect to the
      natural substrate dGTP. For these reasons, the Curie-pyridinones can be
      considered as non-nucleoside inhibitors of HIV-1 RT. Moreover, they have the
      unusual ability to reach the reverse transcription complex inside the
      extracellular virions and may therefore be useful as retrovirucides. This might
      lead to the design and synthesis of new drugs able to interact with the
      retroviral enzyme inside the viral core.

PMID- 15989524
TI  - Medications for the treatment of narcolepsy.
AB  - Narcolepsy is a syndrome of unknown aetiology characterised by excessive daytime
      sleepiness (often severe) usually in association with cataplexy (brief episodes
      of partial or complete muscle paralysis) and often with other uncommon symptoms.
      Due to limited disease-specific knowledge, medication treatment for this
      condition has focussed on specific symptom amelioration rather than improving or
      eliminating underlying disease mechanisms. Such treatment generally consists of
      stimulants for daytime sleepiness and anticataplectic medication for cataplexy;
      hence, both types of agents are reviewed in this article. Recent discoveries,
      including the finding that canine familial narcolepsy is caused by a single gene
      defect in the hypocretin receptor, coupled with the findings in human
      narcoleptics of undetectable hypocretin levels in the CSF and of severe
      hypocretin-containing neuronal atrophy in brains of deceased narcoleptics, have
      shifted the focus of narcolepsy treatment research to the hypocretin system. The
      hope is that a single agent can be developed to provide effective treatment for
      all symptoms of narcolepsy. While the mechanism of action in narcolepsy is
      unknown, gamma-hydroxybutyrate (GHB) is proving to be such an agent.
      Interestingly, GHB is not known to impact hypocretin pathways in the brain, yet
      specific research exploring this possible interaction has not been performed. The
      market for medications limited to use by narcoleptics is small because of the
      relatively low prevalence of narcolepsy; however, the prevalence of clinically
      important daytime sleepiness and/or fatigue is surprisingly high. New agents that
      effectively manage the sleepiness of narcolepsy thus have a much larger potential
      for appropriate use in treating sleepiness and fatigue in the general population.
      This fact has recently been demonstrated by the tremendous success of modafinil,
      a drug introduced to the market a little over 2 years ago, which was developed to
      treat sleepiness in narcolepsy but now is used in a much larger patient
      population.

PMID- 15989525
TI  - Emerging drugs for neuropathic pain.
AB  - Although there are many analgesics on the market for the treatment of nociceptive
      pain, there are none with FDA approval for the treatment of neuropathic pain.
      With a better understanding of the anatomy and physiology of pain, there is a
      significant effort in developing new drugs that interact specifically with pain
      pathways. This higher drug specificity is likely to result in drugs that are more
      efficacious with fewer side effects. This has led to the development of many
      drugs for the treatment of neuropathic pain. These drugs are divided into the
      following therapeutic classes: 1) N-methyl-D-aspartate (NMDA) receptor
      antagonists, 2) ion channel antagonists, 3) alpha2-agonists, 4) nicotinic
      receptor agonists, 5) prostaglandin receptor antagonists, 6) adenosine agonists
      and adenosine kinase inhibitors, 7) neuropeptide antagonists, and 8) prosaposins.
      The results of preclinical and clinical trials are promising for these new
      agents. Whether these agents will be efficacious as single agents is yet to be
      determined; however, preliminary results show that combination therapy may be
      more beneficial with fewer side effects.

PMID- 15989526
TI  - Biological activity of plant extracts: novel analgesic drugs.
AB  - The plant-derived secondary metabolites have, over the years, greatly contributed
      to our current understanding of the important mechanisms related to the process
      of pain transmission and treatment. Furthermore, they have permitted us to
      characterise receptor types and identify endogenous ligands involved in the
      mechanism of nociception. In this review, we discuss the recent advances that
      have occurred regarding plant-derived substances in the process of development of
      new analgesic drugs. Plants, such as Papaver somniferum, Cannabis sativa and
      those of the Capsicum and Salix species, have greatly accounted for the
      development of clinically relevant drugs which are useful for the management of
      pain disorders. The recent advances in our understanding of the mechanisms of
      action of the above plant-derived substances, together with use of molecular
      biology techniques, have greatly accelerated attempts to identify promising
      targets for the discovery of new, safe and efficient analgesic drugs. Despite the
      great progress which has occurred in the elucidation of pain transmission and
      despite decades of use, leaving aside its known undesirable sides effects,
      morphine continues to be one of the most used drugs in clinical practice for the
      treatment of pain disorders. Thus, safer and more efficacious analgesic drugs are
      urgently needed. A search through the literature reveals that many potentially
      active antinociceptive plant-derived compounds have been identified. However,
      studies aiming to investigate their cellular and molecular mechanisms of action
      and well-controlled clinical trials to prove their efficacy in humans are still
      lacking. Nevertheless, natural or synthetic substances that bind to vanilloid or
      cannabinoid receptors, or even those that are capable of modulating the
      endogenous ligands which bind to these receptors, are expected to soon appear to
      assist in the treatment of several pain disorders, including those of neuropathic
      or neurogenic origin.

PMID- 15989527
TI  - Pharmacological treatment for prevention of restenosis.
AB  - Coronary artery disease (CAD) is the leading cause of mortality and morbidity
      among adults in the Western world. Coronary artery bypass grafting and
      percutaneous coronary interventions (PCI) have gained widespread acceptance for
      the treatment of symptomatic CAD. There has been an explosive growth worldwide in
      the utilisation of PCI, such as balloon angioplasty and stenting, which now
      accounts for over 50% of coronary revascularisation. Despite the popularity of
      PCI, the problem of recurrent narrowing of the dilated artery (restenosis)
      continues to vex investigators. In recent years, significant advances have
      occurred in the understanding of restenosis. Two processes seem to contribute to
      restenosis: remodelling (vessel size changes) and intimal hyperplasia (vascular
      smooth muscle cell [VSMC] proliferation and extracellular matrix [ECM]
      deposition). Despite considerable efforts, pharmacological approaches to decrease
      restenosis have been largely unsuccessful and the only currently applied modality
      to reduce the restenosis rate is stenting. However, stenting only prevents
      remodelling and does not inhibit intimal hyperplasia. Several potential targets
      for inhibiting restenosis are currently under investigation including platelet
      activation, the coagulation cascade, VSMC proliferation and migration, and ECM
      synthesis. In addition, new approaches for local drug therapy, such as drug
      eluting stents, are currently being evaluated in preclinical and clinical
      studies. In this article, we critically review the current status of drugs that
      are being evaluated for restenosis at various stages of development (in vitro,
      preclinical animal models and human trials).

PMID- 15989528
TI  - Drugs targeted against protein kinases.
AB  - Current treatments for cancer (surgery, radiation and chemotherapy) are
      successful for early stage localised disease but have severe side effects. New
      treatments are needed to increase the cure rate and life expectancy of patients.
      With the discovery of oncogenes, tumour suppressor genes and an understanding of
      their role in the development of the malignant disease, a new era of therapy has
      begun. Cancer is a manifestation of deregulated signalling pathways that mediate
      cell growth and programmed cell death. Protein kinases are essential elements in
      these signalling pathways. In the US, Novartis launched Gleevec (imantinib, STI
      571) in May 2001 as the first anticancer drug whose mechanism of action is kinase
      inhibition. In Phase I trials, 23/24 patients with chronic myelogenous leukaemia
      (CML) had complete remissions and the drug is relatively non-toxic. Herceptin
      (trastuzumab) is a monoclonal antibody (mAb) against a member of the growth
      factor receptor family (HER-2/neu) that was launched in 1998 by Genentech for the
      treatment of breast cancer. Trastuzumab has an excellent antitumour profile,
      particularly when used in combination with doxorubicin and paclitaxol. These
      drugs are pioneering the treatment of cancer based on the molecular understanding
      of the disease. Numerous drugs that target growth factor receptors and their
      signalling pathways are in advanced clinical trials. Herein, antibodies against
      receptors and small molecule inhibitors of kinases in signalling pathways will be
      summarised. Inter-disciplinary preclinical studies have identified chemicals that
      target specific kinases. We believe that clinical studies of these agents will
      yield new anticancer agents that target specific diseases and that are less toxic
      than current agents.

PMID- 15989529
TI  - A therapeutic area review of oncology products and players.
AB  - This article reviews the dynamics of the oncology market and treatment trends and
      provides strategic guidance to those concerned with new product discovery and
      development. Cancer is the therapeutic area of highest potential, with an annual
      market value expected to be in excess of US 40 billion dollars in 2020. The
      global incidence of cancer cases is forecast to more than double over the next 20
      years. Investments in research and development will keep pace with the growing
      demand for effective treatments, aiming to fulfil the many and often discrete
      unmet medical needs. Recent breakthroughs promise more successful outcomes,
      particularly with the advent of more selective chemotherapy and novel therapeutic
      approaches. Among the latter, a number of angiogenesis inhibitors and monoclonal
      antibodies (mAbs) should show encouraging levels of efficacy by 2004. Oncology is
      a complex and high-risk therapeutic area that offers high rewards. It is
      appropriate for only the stronger or more focused serious players within the
      pharmaceutical industry. The winners will be the companies with a long-term
      strategic intent, a credible portfolio and engagement in appropriate alliances,
      particularly in discovery. The future presents ethical, clinical and commercial
      challenges, given the wide disparity of therapeutic outcomes among cancer
      patients around the world. The real success will thus be to treat cancer in
      innovative ways that benefit everyone and are, in volume and across the life
      cycle, commercially attractive to the treatment provider.

PMID- 15989530
TI  - Synthetic polymer systems in drug development.
AB  - The use of synthetic polymers in drug discovery is reviewed, with particular
      reference to the increasing number of chemistries for therapeutic candidate
      preparation that employ linear polymers possessing differential solubilities in a
      variety of solvents. The uses of these polymers as primary components in liquid
      phase organic synthesis, particularly applied to the generation of chemical
      compound libraries, are discussed, along with the challenges facing synthetic
      chemists and pharmaceutical scientists in preparing new and more efficient
      supports. The advantages inherent to the emerging field of liquid-phase
      combinatorial synthesis (LPCS) are considered and a number of key therapeutic
      targets prepared by newer polymer-supported routes are highlighted. Finally, the
      potential development issues for both liquid and solid-phase organic chemistries
      applied to parallel or combinatorial synthesis are discussed, taking into account
      future trends in the drug discovery and development process as a whole.

PMID- 15989531
TI  - Synthetic polymer systems in drug delivery.
AB  - The development of synthetic polymers for applications in drug delivery is
      reviewed, with particular reference to polymers that can be activated to release
      a medicinal agent in vivo or that can respond to changes in environment to
      enhance the effectiveness of therapy. The mechanisms by which these polymers are
      designed to deliver drugs are highlighted, along with the challenges facing
      synthetic chemists and pharmaceutical scientists in designing new and more active
      therapeutic vehicles. Currently, synthetic materials with biomimetic properties
      are attracting growing attention as possible new dosage formulations and the
      potential applications of these increasingly sophisticated polymers in cell
      specific drug targeting and in the emerging field of gene therapy are also
      considered. Finally, the potential development issues for delivery of
      therapeutics using active or 'smart' polymers are discussed with an analysis of
      the future trends in this rapidly expanding area of research.

PMID- 15989532
TI  - Advances in the therapeutic modulation of angiogenesis.

PMID- 15989533
TI  - New agents for the treatment of systemic fungal infections--current status.
AB  - Systemic antifungal chemotherapy is enjoying its most dynamic era. More
      antifungal agents are under development than ever before, including agents in
      entirely new classes. Major goals of current investigations are to identify
      compounds with a wide spectrum of activity, minimal toxicity and a high degree of
      target specificity. The antifungal drugs in development include new azoles
      {voriconazole, posaconazole (formerly SCH-56592), ravuconazole (formerly BMS
      207147)}, lipid formulations of amphotericin B, a lipid formulation of nystatin,
      echinocandins {anidulafungin (formerly, LY-303366, VER-002), caspofungin
      (formerly MK-991), micafungin (formerly FK-463)}, antifungal peptides other than
      echinocandins, and sordarin derivatives. This discussion reviews the currently
      available antifungal agents and summarises the developmental issues that surround
      these new systemic antifungal drugs.

PMID- 15989534
TI  - Pharmacological agents in development for invasive aspergillosis.
AB  - The urgent medical need for new potent antifungal agents in the management of
      invasive aspergillosis (IA) has resulted in the development of several compounds
      which may be of value in the future for the treatment or prophylaxis of IA. In
      the past years, several novel types of drugs have been discovered and developed,
      some of which are already in late-stage clinical trials and ready to enter the
      market. This paper discusses the antifungal agents, classified by their mode of
      action, that are currently available and the agents which are still in
      development for treatment or prevention of IA.

PMID- 15989535
TI  - Histatin-derived peptides: potential agents to treat localised infections.
AB  - Histatins are a family of histidine-rich, cationic peptides composed of up to 38
      amino acids. They are secreted by the salivary glands of humans and some subhuman
      primates and are thought to be part of the host defence system in the oral
      cavity. Histatins exhibit in vitro activity against both bacteria and yeast,
      common to other antimicrobial peptides. Because of these activities, histatin
      based peptides could play an important role in the treatment and prevention of
      infectious diseases. A 12 amino acid amidated fragment of histatin 5, designated
      P-113, has been identified as the smallest fragment that retains antimicrobial
      activity comparable to the parent compound. Animal studies and human clinical
      trials showed that P-113 has potential in preventing the development of
      gingivitis, with no adverse side effects. Histatin peptides also could be used
      for other therapeutic applications in which the infection is localised and
      accessible via topical delivery, such as treatment of candidiasis (thrush) and
      mucositis in the oral cavity, skin infections and treatment of lung infections
      afflicting cystic fibrosis patients.

PMID- 15989536
TI  - Developments in the treatment of leishmaniasis and trypanosomiasis.
AB  - The leishmaniases and trypanosomiases are diseases caused by related parasites
      belonging to the kinetoplastidae family. They share common biological traits,
      which are comparatively better known than for other parasites, and which would
      favour the identification of common targets. Yet, very few new drugs are on the
      horizon and treatment relies on old, often toxic and ineffective drugs.
      Miltefosine may soon become the first oral drug registered for Leishmaniasis.
      Other compounds in clinical trials are paromomycin, sitamquine and lipid
      formulations of amphotericin B. For African trypanosomiasis old drugs primarily
      indicated for Chagas disease are being considered (nifurtimox, megazole). Earlier
      projects are berenil, bisamidines and triazines for African trypanosomiasis, and
      novel azoles and cruzipain inhibitors for Chagas disease.

PMID- 15989537
TI  - Emerging drugs in psoriasis.
AB  - Psoriasis is a relatively common, chronic skin disease affecting 1-2% of the
      population in the developed countries. It is an inflammatory, autoimmune skin
      disorder characterised by an accelerated rate of epidermal proliferation and
      disordered differentiation. Since our last review in 1999, considerable progress
      has been made in understanding the immunopathogenesis of this disease, and new
      drugs have become available for its treatment. Recent clinical trials showed the
      efficacy of novel biotechnology approaches, such as blocking tumour necrosis
      factor-alpha or T-cell-mediated immune response by the anti-CD2, anti-CD11a, anti
      B7, anti-CD4 or anti-CD25 approaches. Agents which block type 1 cytokines or skew
      immune reactions into type 2 are other promising approaches. Other possible
      targets are chemokines and their receptors, the cytokines and receptors involved
      in T cell trafficking into the skin, and peroxisome proliferator-activated
      receptors. Relatively little development is reported of the drugs targeting the
      keratinocyte or the classical antipsoriatic compounds which include
      glucocorticoids, vitamin D derivatives and cytostatic agents.

PMID- 15989538
TI  - New and emerging treatments for irritable bowel syndrome and functional
      dyspepsia.
AB  - The symptomatic management of irritable bowel syndrome (IBS) and functional
      dyspepsia, which often overlap, can be frustrating and difficult. Education and
      reassurance remain central for management although controlled trials are lacking.
      Psychological interventions may be useful in select patients but methodological
      inadequacies in clinical trials limit their interpretability. For symptom
      exacerbations, drug treatment is reasonable but no current treatment successfully
      targets the full symptom complex. Bulking agents are not of proven efficacy in
      IBS; they may improve constipation but worsen bloating and pain. Anticholinergics
      are of uncertain value in IBS. A meta-analysis of trials of smooth muscle
      relaxants for IBS has been reported to be positive but the quality of the trials
      included was poor. Antidepressants for IBS and functional dyspepsia appear to be
      efficacious based on the limited published evidence; both global symptoms and
      abdominal pain improve. Selective serotonin reuptake inhibitors (SSRIs) are of
      uncertain efficacy but anecdotally appear to be useful. Laxatives are not of
      proven efficacy in IBS. Loperamide improves diarrhea, but not abdominal pain in
      IBS. No drug is of proven efficacy for bloating. Acid suppression remains the
      mainstay of therapy for functional dyspepsia but the majority of patients do not
      have an adequate response. Promising drugs include new prokinetics for
      constipation-predominant IBS (e.g., tegaserod, a partial 5-HT4 agonist,
      prucalopride, a full 5-HT4 agonist, and dexloxiglumide, a cholecystokinin1
      antagonist), agents for diarrhea-predominant IBS (e.g., 5-HT3 antagonists, alpha2
      receptor agonists and corticotrophin receptor-1 antagonists), other visceral
      analgesics (e.g. tachykinin antagonists, opioid agonists) and in dyspepsia fundus
      relaxing agents (e.g., 5-HT1 agonists, tegaserod).

PMID- 15989539
TI  - Cellular mechanisms for the treatment of chronic heart failure: the nitric oxide-
      and adenosine-dependent pathways.
AB  - Accumulated evidence suggests that several drugs proven to improve survival in
      patients with chronic heart failure (CHF) enhance endogenous nitric oxide (NO)-
      and/or adenosine-dependent pathways. Indeed, we and others have demonstrated
      that: i) antagonists of either renin-angiotensin-aldosterone or beta-adrenergic
      systems enhance NO-dependent pathways; ii) although carvedilol and amlodipine
      belong to different drug classes, both of them can increase cardiac adenosine
      levels; iii) increased adenosine levels by dipyridamole are associated with the
      improvement of CHF. Interestingly, both NO and adenosine have multifactorial
      beneficial actions in cardiovascular systems. First of all, both of them induce
      vasodilation and decrease myocardial hypercontractility, which may contribute to
      a reduction in the severity of myocardial ischaemia. Both adenosine and NO are
      also involved in cardioprotection attributable to acute and late phases of
      ischaemic preconditioning, respectively. Secondly, they can modulate the
      neurohormonal systems that contribute to the progression of CHF. Thus, we propose
      that enhancement of endogenous NO and/or adenosine as potential therapeutic
      targets in a new strategy for the treatment for CHF.

PMID- 15989540
TI  - Antithrombotic agents in the treatment of severe sepsis.
AB  - Sepsis, a systemic inflammatory syndrome, is a response to infection and when
      associated with multiple organ dysfunction is termed severe sepsis. It remains a
      leading cause of mortality in the critically ill. The response to the invading
      microorganisms may be considered as a balance between a pro-inflammatory and an
      anti-inflammatory reaction. While an inadequate pro-inflammatory reaction and a
      strong anti-inflammatory response could lead to overwhelming infection and the
      death of the patient, a strong and uncontrolled pro-inflammatory response,
      manifested by the release of pro-inflammatory mediators may lead to microvascular
      thrombosis and multiple organ failure. Endotoxin triggers sepsis via the release
      of various mediators such as tumour necrosis factor-alpha and interleukin-1 (IL
      1). These cytokines activate the complement and coagulation systems, release
      adhesion molecules, prostaglandins, leukotrienes, reactive oxygen species and
      nitric oxide. Other mediators involved in the sepsis syndrome include IL-1, -6
      and -8; arachidonic acid metabolites; platelet activating factor; histamine;
      bradykinin; angiotensin; complement components and vasoactive intestinal peptide.
      These pro-inflammatory responses are counteracted by IL-10. Most of the trials
      targeting the different mediators of the pro-inflammatory response have failed
      due to a lack of correct definition of sepsis. Understanding the exact
      pathophysiology of the disease will enable more advanced treatment options.
      Targeting the coagulation system with various anticoagulant agents including,
      activated protein C, and tissue factor pathway inhibitor (TFPI) is a rational
      approach. Many clinical trials have been conducted to evaluate these agents in
      severe sepsis. While trials on antithrombin and TFPI were not so successful, the
      double-blind, placebo-controlled, Phase III trial of recombinant human activated
      Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) was successful,
      creating a significant decrease in mortality when compared to the placebo group.
      A better understanding of the pathophysiologic mechanism of severe sepsis will
      provide better treatment options, and combination antithrombotic treatment may
      provide a multipronged approach for the treatment of severe sepsis.

PMID- 15989541
TI  - Advances in glaucoma therapeutics.
AB  - Glaucoma is a major cause of irreversible blindness in the world. The prevalence
      of glaucomatous loss in vision will continue to grow as our populations age.
      Ocular hypertension is a major risk factor for the development of glaucoma and
      current glaucoma therapy is directed at lowering intraocular pressure. Several
      new ocular hypotensive agents have been introduced in the past several years
      providing a variety of treatment options. In addition, various classes of
      neuroprotective agents demonstrating activity in a wide variety of animal models
      have been proposed as potential new glaucoma therapeutics. Although these
      approaches will slow the progression of vision loss, they do not directly
      intervene in the disease process(es). Advances have been made attempting to
      understand the pathogenic pathways involved in glaucomatous damage to the eye and
      in methods to clinically measure glaucoma damage. An increased understanding of
      the pathophysiology of glaucoma will lead to the development of new therapeutic
      agents that intervene and perhaps even reverse glaucomatous damage to the eye.
      There also is a need to develop new methods to clinically measure glaucoma damage
      because, currently, considerable damage occurs before glaucoma is diagnosed and
      glaucoma remains underdiagnosed in the general population.

PMID- 15989542
TI  - Insulin-sensitising agents: beyond thiazolidinediones.
AB  - The global prevalence of Type 2 diabetes mellitus is increasing rapidly, at least
      in part as a function of obesity. The results of the United Kingdom Prospective
      Diabetes Study emphasise the importance of developing safe, efficacious new
      agents for the treatment of Type 2 diabetes. The pharmaceutical industry has
      recently focused on strategies to improve insulin resistance, particularly
      modulation of PPAR-gamma. Here we review current thinking on the mechanism of
      action of these agents, and consider future directions that may arise as a result
      of increasing understanding of the biology of these receptors and of insulin
      action. Studies of thiazolidinedione action in adipose tissue have revealed
      several novel adipocyte-derived hormones that may also be future pharmacological
      targets for increasing insulin sensitivity. The role of other hormones, such as
      cortisol and dehydroepiandrosterone, are also discussed in a therapeutic context,
      as are other novel approaches to the pharmacological management of patients with
      insulin resistance and Type 2 diabetes.

PMID- 15989543
TI  - Growth factors in haematological cancers.
AB  - Since their discovery just under a century ago, growth factors (GFs) have been
      used almost ubiquitously in haematology. Many haematological cancers are
      associated with bone marrow failure, either as a direct consequence of the
      disease or its treatment. Colony stimulating factors (CSFs) have been used to
      address the problems associated with the resulting cytopenias, however, concerns
      about the potential leukaemogenic effects of some of these CSFs led to a degree
      of initial hesitancy in usage, particularly in the management of acute myeloid
      leukaemia (AML). This has now been largely overcome. Other limitations have
      included cost and side effect profiles (the latter particularly with the
      multilineage factors). There has been wide variation locally, nationally and
      internationally in the usage of GFs. The American Society of Clinical Oncologists
      (ASCO) attempted to rationalise the usage of GFs by producing a consensus
      document enumerating the evidence-based indications for use of GFs. There is
      little information on cost effectiveness, this remains an important issue for the
      future. Peripheral blood stem cell transplantation (PBSCT) has revolutionised the
      management of many malignant conditions and has contributed to the increased use
      of growth factors. Many other indications are emerging for GFs used singly or in
      combination. Current clinical applications of GFs include: i) amelioration of
      cytopenias following chemotherapy and stem cell transplantation, ii) chemotherapy
      dose maintenance and escalation, iii) chemosensitisation and modification of
      disease states, iv) optimisation of methods for mobilisation of progenitor stem
      cells, v) immunotherapy, and vi) as therapeutic targets for treatment of
      haematolgical malignancies.

PMID- 15989544
TI  - New hope for neglected diseases.

PMID- 15989545
TI  - Emerging melanoma vaccines.

PMID- 15989546
TI  - Inhibition of bacterial efflux pumps: a new strategy to combat increasing
      antimicrobial agent resistance.
AB  - Resistance to multiple drugs in medically important bacteria results in
      therapeutic challenges for the clinician. The mechanisms by which bacteria evade
      the effects of antimicrobial agents are many, but in recent years it has become
      apparent that efflux is a significant means of resistance and probably explains
      the intrinsic resistance to numerous drugs observed in species such as
      Pseudomonas aeruginosa. Drug efflux is mediated by membrane-based hydrophobic
      proteins belonging to several distinct families, the members of which are related
      by structural characteristics, mechanism of action and energy source for the
      transport process. The multi-drug efflux transporters are particularly
      problematic as they are capable of extruding numerous structurally dissimilar
      drugs. Inhibition of these pumps, and even those with more limited substrate
      specificity, has been shown to decrease intrinsic resistance, reverse acquired
      resistance and reduce the emergence of mutants with higher-level target-based
      mutational resistance. Combining broad spectrum efflux pump inhibitors with
      current drugs that are pump substrates can recover clinically relevant activity
      of those compounds and thus may reduce the need for the discovery and development
      of new antimicrobial agents that are not pump substrates. Additional effort
      toward the identification, characterisation and determination of the clinical
      utility of efflux pump inhibitors is warranted.

PMID- 15989547
TI  - Anti-TNF agents for the treatment of spondyloarthropathies.
AB  - For the treatment of spondyloarthropathies (SpA), therapeutic options using
      disease-modifying drugs are rather limited compared to other inflammatory
      rheumatic diseases such as rheumatoid arthritis (RA). This is especially true for
      the spinal symptoms of the spondyloarthropathies, of which ankylosing spondylitis
      (AS) is the prototype. New TNF-alpha blockers have been proven highly effective
      in improving the spinal symptoms and extra-spinal manifestations of SpA.
      Convincing data in the form of placebo-controlled trials are already available
      for AS and psoriatic arthritis (PsA). However, limited data suggests that TNF
      alpha blockers might be similarly effective in other spondylolarthropathies. Side
      effects, mainly infections and allergic reactions, occur similar to those
      observed in RA treatment. Currently, there is no reason to combine TNF-alpha
      blockers with other disease-modifying anti-rheumatic drugs (DMARDs) for the
      treatment of AS and other SpA, as these DMARDs are not effective. Thus, TNF-alpha
      blockers seem to be a major breakthrough in the treatment of SpA. The patients
      who are primary candidates for such treatments are yet to be defined,
      particularly in light of the high costs and unknown long-term side effects
      involved. Furthermore, future studies need to show whether these biologicals not
      only suppress inflammation but also prevent long-term bony damage.

PMID- 15989548
TI  - Emerging therapies for heart failure.
AB  - Although multiple advancements have been made in the treatment of heart failure
      (HF), mortality rates remain alarmingly high. The accepted arsenal of
      therapeutics includes a diuretic, digitalis, a beta-blocking agent and an
      inhibitor of the renin-angiotensin-aldosterone system. Despite the employment of
      a vast array of agents, nearly 300,000 patients in the US die annually with HF as
      a primary or contributory cause of death. Additional molecular targets are being
      evaluated in preclinical and clinical settings including vasopeptidase
      inhibitors, endothelin-1 receptor antagonists, arginine vasopressin antagonists,
      selective aldosterone blockers, TNF-alpha blockers and matrix metalloproteinase
      inhibitors. Although these approaches hold promise as viable therapeutics, a
      thorough evaluation of clinical benefit from these agents requires additional
      trials. Future disease-modifying approaches will also undoubtedly include cell
      transplantation and gene therapy. It is likely that notable advances in HF
      treatment will come from agents that attenuate myocardial remodelling. Indeed,
      maintenance or improvement of cardiac structure can attenuate HF development and
      improve mortality.

PMID- 15989549
TI  - The immediate future for the medical treatment of atrial fibrillation.
AB  - Atrial fibrillation is the most commonly sustained cardiac arrhythmia and a
      common reason for mortality and morbidity. Atrial fibrillation causes disease for
      three reasons: i) the ventricular rate is often high, which leads to symptoms
      ranging from discomfort to life threatening heart failure; ii) the rhythm causes
      loss of atrioventricular synchrony, which reduces diastolic filling and may lead
      to heart failure; and iii) atrial contraction is lost leading to stagnant blood
      that again may lead to atrial thrombi and peripheral embolism. Thus, the
      treatment of atrial fibrillation is focused on the maintenance of sinus rhythm,
      rate control and prevention of embolism. For the maintenance of sinus rhythm, all
      drugs under current development are potassium channel blockers; the so-called
      class III anti-arrhythmic drugs. Those which have been further investigated
      appear to be valuable for maintenance of sinus rhythm but all carry a significant
      risk of pro-arrhythmia, in particular Torsade de Pointe ventricular tachycardia.
      Rate control has been a focus of treatment for many years and several very old
      drugs, including digoxin, are used for this. There is, to the author's knowledge,
      no current effort for evaluating new drugs for this indication. Prevention of
      embolism has for many years been obtained with vitamin K antagonists for which
      the clinical evidence is overwhelming. Previous attempts to replace vitamin K
      antagonists with aspirin have not been fruitful. A large number of newer
      anticoagulation regimes are in development, but to the author's knowledge only a
      single thrombin inhibitor is actively being developed for atrial fibrillation.

PMID- 15989550
TI  - New drugs for treatment of attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is one of the longest recognised
      and most common neuropsychiatric disorders of childhood. Recent research
      indicates that ADHD is most often a lifelong condition associated with
      significant impairment in multiple domains of functioning. ADHD is a clinical
      diagnosis made on the basis of history and clinical examination. Current
      molecular, neuroimaging and neuropsychological studies have greatly elucidated
      our understanding of the basic science of ADHD. The underlying pathophysiology of
      ADHD has been theorised to be dysregulation of inhibitory noradrenergic
      frontocortical activity on dopaminergic striatal structures. Pharmacotherapy is
      recognised as the most effective component of ADHD treatment, although some role
      exists for proper educational placement, parent management training and social
      skills development. Methylphenidate and amphetamine are the current standards in
      ADHD medication treatment. Other medication classes such as tricyclic
      antidepressants and certain antihypertensives are also used in off-label therapy.
      Anticipated improvements in new ADHD medications include the development of
      extended release delivery systems, improved tolerability, alternative mechanisms
      of action and enhanced efficacy in treatment refractory cases.

PMID- 15989551
TI  - Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents.
AB  - Heat-shock protein 90 (Hsp90) is a molecular chaperone whose association is
      required for the stability and function of multiple mutated, chimeric and
      overexpressed signalling proteins that promote cancer cell growth and/or
      survival. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt,
      HER2/Neu (ErbB2) and hypoxia inducible factor-1alpha (HIF-1alpha). Through
      specific interaction with a single molecular target, Hsp90 inhibitors cause the
      destabilisation and eventual degradation of Hsp90 client proteins, and they have
      shown promising antitumour activity in preclinical model systems. One Hsp90
      inhibitor, 17-allylamino-geldanamycin (17-AAG), is currently in Phase I clinical
      trials. Hsp90 inhibitors are unique in that, although they are directed towards a
      specific molecular target, they simultaneously inhibit multiple signalling
      pathways on which cancer cells depend for growth and survival. Further, because
      of the unique effect that Hsp90 inhibition has on cancer cells, combination of an
      Hsp90 inhibitor with standard chemotherapeutic agents may dramatically increase
      the in vivo efficacy of the standard agent.

PMID- 15989552
TI  - Rituximab and other emerging monoclonal antibody therapies for lymphoma.
AB  - The recent approval of rituximab, gemtuzumab ozogamicin, alemtuzumab and
      ibritumomab tiuxetan by the FDA in the US revealed clear evidence that monoclonal
      antibodies (mAbs) have significant roles in the current treatment of haematologic
      malignancies. Among the mAbs under clinical development, anti-CD20 mAbs have been
      most extensively investigated and have shown definitive clinical efficacy.
      Rituximab is a genetically engineered chimeric anti-CD20 mAb, with mouse variable
      and human constant regions. Consecutive clinical trials conducted in the US,
      Europe and Japan have revealed that rituximab is a highly effective agent with
      acceptable toxicities against indolent and aggressive B cell non-Hodgkin's
      lymphomas (B-NHLs) as a single agent and in combination with cytotoxic drugs. A
      recent French Phase III study in elderly patients with untreated aggressive B-NHL
      suggested that the addition of rituximab to standard CHOP (cyclophosphamide,
      doxorubicin, vincristine and prednisone) chemotherapy increases the complete
      response rate and prolongs event-free and overall survival. Lymphoma cells are
      inherently sensitive to radiation. The aim of radioimmunotherapy is to use the
      mAb to target radiation to lymphoma tissue while minimising toxicity to normal
      cells. The clinical trials of 90Y ibritumomab tiuxetan and (131)I tositumomab
      showed they have definitive efficacy in relapsed indolent B-NHL with acceptable
      toxicities. A recent comparative study in relapsed indolent B-NHL showed that 90Y
      ibritumomab tiuxetan produces higher response rates than rituximab. In addition,
      BL22, a recombinant anti-CD22 immunotoxin, showed significant efficacy in
      patients with chemotherapy-resistant hairy cell leukaemia. MAbs will have
      significant roles in the treatment of lymphoid malignancies in the future.

PMID- 15989553
TI  - Aromatase inhibitors and other novel agents in breast cancer treatment.
AB  - Thirty years after the introduction of tamoxifen, which was expanded from
      palliation of metastatic cancer to recent application for chemoprevention, the
      primacy of this drug as the mainline pharmacological intervention is currently
      being challenged by the third generation aromatase inhibitors and inactivators.
      In contrast to the oestrogen receptor blockade provided by tamoxifen, aromatase
      inhibitors result in deprivation of oestrogens in postmenopausal women both
      through paracrine/intracrine and endocrine modulation. Experimental evidence has
      shown a significant (97-99%) reduction of in vivo aromatase activity and an equal
      or sometimes better antitumour activity compared with megestrol acetate when
      these drugs are used as second-line treatment for metastatic breast cancer.
      Recent pivotal studies in first-line settings comparing tamoxifen for metastatic
      breast cancer and preliminary results from the neoadjuvant trials demonstrate
      that third generation aromatase inhibitors are superior to tamoxifen. With a
      better understanding of local tissue production of oestrogen through oestrone
      sulfatase, which hydrolyses oestrone sulfate to oestrone, and 17-beta
      hydroxysteroid dehydrogenase Type 1, which in turn catalyses the reduction of
      oestrone to oestradiol, more powerful tactics for oestrogen starvation of cancer
      may be realised in future.

PMID- 15989554
TI  - Photodynamic therapy systems and applications.
AB  - Photodynamic therapy (PDT) is a form of photochemotherapy requiring the
      simultaneous presence of a photosensitiser, activating light of the proper
      wavelength and molecular oxygen in order to produce a localised therapeutic
      effect thought to be due to high-energy singlet oxygen generation. Neither drug
      nor light alone are effective as therapeutic agents and thus PDT treatment
      methods should be looked upon as true, necessary, drug and device combinations
      ('systems'). Selectivity of treatment is imparted by a combination of factors,
      including accumulation of photosensitiser by the target lesion and targeted
      application of activating light. The most common systemic side effect of
      systemically administered photosensitisers is cutaneous photosensitivity of
      varying periods of time. Local toxicities depend on the area of treatment.
      Sources of light which have been used in PDT include lasers, arc lamps, light
      emitting diodes and fluorescent lamps. PDT has been used for a wide variety of
      clinical applications. In 1995, the first PDT system, using porfimer sodium
      (Photofrin, Axcan Pharma, Inc.), lasers and fibre optic light delivery methods,
      developed by QuadraLogic Technologies, was approved in the US for endoscopic
      palliation of malignant dysphagia caused by oesophageal cancer. A topical PDT
      system, aminolevulinic acid HCL (Levulan Kerastick) and the large-area BLU-U PDT
      Illuminator, was developed by DUSA Pharmaceuticals, Inc. for the treatment of
      actinic keratoses of the face and scalp and approved in the US in 2000. Topical
      PDT has applicability to a wide variety of skin cancers and precancerous
      conditions. In 2001, Novartis launched the systemically administered verteporfin
      (Visudyne) laser-based PDT system in the US as the first pharmacologic treatment
      for age-related macular degeneration. Development programmes are continuing to
      investigate PDT for the potential treatment of a variety of diseases, yielding
      therapeutic results with minimal toxicity.

PMID- 15989555
TI  - 38th Annual Meeting of the American Society of Clinical Oncology. 18-21 May 2002,
      Orlando, Florida, USA.
AB  - The American Society of Clinical Oncology 38th Annual Meeting has continued to
      showcase an increasing number of biological and targeted therapies for the
      treatment of cancer and its complications. This review will provide an overview
      of the posters and presentations describing novel biological agents.

PMID- 15989556
TI  - Cytokine networks in allergic lung inflammation: an opportunity for drug
      intervention.
AB  - Eosinophils and mast cells have long been considered as the major effector cells
      ultimately responsible for bronchial obstruction and airway hyper-responsiveness
      in asthmatics. However, there is now accumulating evidence that products of Th2
      lymphocytes may orchestrate the generation, accumulation, and activation of these
      cells within the airway wall. Since the first report by Mosmannet al. in 1986
      that murine helper T-cell clones could be divided into two subsets, Th1 and Th2,
      depending on their pattern of cytokine secretion, and observations that
      polarisation of Th1- or Th2-dependent cytokine production could be correlated
      with distinct autoimmune and allergic disorders, there has been an increasing
      interest in the possibility that pharmacological manipulation of the Th1/Th2
      paradigm could provide novel treatments for human disease. This review summarises
      the evidence to date, attempts to explain some apparent discrepancies, and
      indicates opportunities for therapeutic intervention.

PMID- 15989557
TI  - The immunomodulatory actions of E-type prostaglandins.
AB  - Prostaglandins (PGs) have been recognised as modulators of immune responses. This
      has been proved by both in vitro studies and from observations in animals and
      humans. Administration of prostaglandins for therapeutic purposes, however, has
      been hampered by their limited bioavailability and their pleiotropic effects,
      with resultant toxicological profile. Despite this, some success has been
      demonstrated in the clinic for the control of graft rejection, especially when
      used as part of a broader immunosuppressant regimen. Full realisation of the
      therapeutic potential of prostaglandins will depend on a better understanding of
      their mechanism of action at the cellular level. Recently, it has been
      appreciated that prostaglandins do not merely inhibit T-cell function, but appear
      to modulate the profile of lymphocyte sub-populations through regulation of
      cytokine synthesis and release. Recent efforts have also begun to focus on
      identifying prostaglandin receptor subtypes important for immune regulation and
      offer a means, together with targeted delivery, of utilising the
      immunosuppressant/anti-inflammatory effects of E-type prostaglandins in a safe
      and effective manner.

PMID- 15989558
TI  - Nicotine: therapeutic potential for the treatment of ulcerative colitis.
AB  - Ulcerative colitis (UC) is predominantly a disease of non-smokers, and nicotine
      may be the agent responsible for this association. Transdermal nicotine has been
      shown to improve disease activity and sigmoidoscopic appearance in the active
      disease but in one study had no effect on maintenance of remission. Since side
      effects with nicotine patches occur in up to two thirds of patients, attempts to
      reduce systemic levels and improve drug tolerance have been developed with
      colonic delivery systems of nicotine. Preliminary observations with nicotine
      enemas in UC have shown clinical benefit, but controlled trials are needed.
      Mechanisms responsible for the association of smoking with colitis and for the
      therapeutic effect of nicotine remain an enigma; possibilities include:
      modulation of the immune response, alterations of colonic mucus and eicosanoid
      production, changes in rectal blood flow, decreased intestinal permeability and
      the release of endogenous glucocorticoids. With current treatment for UC limited
      to corticosteroids and formulations of 5-aminosalicylic acid, alternative
      treatments are required and nicotine may fulfil this role.

PMID- 15989559
TI  - Do beta-blockers have a role in the treatment of chronic heart failure?
AB  - There has been growing interest in and recognition of the role of beta-blockers
      in chronic heart failure (CHF). The mode of action is complex and several
      mechanisms have been proposed. The principal rationale for the use of beta
      blockade is to counteract neurohormonal activation and its deleterious
      consequences in CHF. While the positive effect of this treatment on
      haemodynamics, exercise tolerance and quality of life, and a clear trend in
      favour of improved prognosis have been shown, there is still no concrete proof
      that beta-blockers reduce mortality in CHF. Several large-scale, prospective,
      randomised, placebo-controlled trials, designed to provide a definitive answer,
      are underway.

PMID- 15989560
TI  - Planned, ongoing and recently completed clinical trials for atherosclerosis
      prevention and regression: an update.
AB  - Recent landmark studies using hydroxy-methyl-glutaryl-Co-enzyme A reductase
      inhibitors (HMG-CoA reductase inhibitors or statins), specifically, pravastatin
      and simvastatin, have led to dramatic changes in medical practice. These clinical
      trials have demonstrated that clinicians can impact coronary morbidity and
      mortality in primary (pravastatin) and secondary (pravastatin, simvastatin)
      prevention settings, including post-infarct patients with 'normal' cholesterol
      levels (pravastatin). The clinical benefit can be seen irrespective of risk
      factors at baseline and in women, the elderly and diabetics.

PMID- 15989561
TI  - Leflunomide and malononitriloamides.
AB  - Leflunomide is a new immunomodulatory drug effective in experimental models of
      autoimmune diseases and allo- or xenotransplantation. In a Phase II clinical
      trial leflunomide has shown high tolerability and efficacy in patients with
      advanced rheumatoid arthritis. The immunomodulatory activity of leflunomide is
      attributed to its primary metabolite, A77 1726, a malononitriloamide. The in
      vitro and in vivo mechanisms of action of this class of compounds remain to be
      completely defined. A77 1726 and several malononitriloamide analogues inhibit T-
      and B-cell proliferation, suppress immunoglobulin production, and interfere with
      cell adhesion. While no one central molecular mechanism of action has been
      proposed to explain all the effects of the malononitriloamides, inhibition of de
      novo pyrimidine biosynthesis and inhibition of cytokine- and growth factor
      receptor associated tyrosine kinase activity are leading hypotheses for the
      effects of A77 1726 on T- and B-cell proliferation and function. Leflunomide is
      effective when administered at daily doses of 10 and 25 mg to patients with
      active rheumatoid arthritis. The improved efficacy at the 25 mg dose is
      associated with a higher incidence of adverse effects (gastrointestinal symptoms,
      weight loss, allergic reactions, skin rash, and reversible alopecia). Due to the
      long plasma half-life of A77 1726 (11-16 days), loading doses are required to
      achieve steady-state concentrations. Phase III randomised, placebo-controlled
      trials using daily doses of 10 or 20 mg are underway in the US and Europe to
      confirm and extend the results of the Phase II study. Malononitriloamide
      analogues of A77 1726 are being evaluated for immunosuppressive efficacy in
      preclinical models of transplantation, because these compounds have a shorter
      half-life in animals than A77 1726. If these analogues show efficacies similar to
      leflunomide in these models and have shorter half-lives than A77 1726 in Phase I
      trials, the preclinical and Phase I data will be used to select the analogues for
      Phase II trials in organ transplant recipients.

PMID- 15989562
TI  - Venlafaxine:a novel antidepressant compound.
AB  - Venlafaxine is a new antidepressant that inhibits the reuptake of both 5
      hydroxytryptamine (serotonin; 5-HT) and noradrenaline (NA). It is somewhat more
      potent as an inhibitor of the reuptake of 5-HT than NA. Its potency to inhibit
      the reuptake of 5-HT is comparable to that of tricyclic antidepressants (TCAs)
      such as amitriptyline or imipramine, but it is less potent than these drugs at
      inhibiting the reuptake of NA. Consequently, at low doses, venlafaxine may be a
      more effective inhibitor of the reuptake of 5-HT than that of NA. The major
      metabolite of venlafaxine in humans, O-desmethylvenlafaxine, has comparable
      potency to the parent drug for inhibiting the reuptake of either NA or 5-HT in
      vitro, but it is less potent in vivo. Both venlafaxine and O-desmethylvenlafaxine
      are essentially devoid of activity at muscarinic cholinergic, H1 histaminergic,
      and 1-adrenoceptors. This probably accounts for venlafaxine having a side-effect
      profile similar to that of selective serotonin reuptake inhibitors (SSRIs) rather
      than that of TCAs. Venlafaxine is subject to extensive first-pass metabolism and
      is metabolised by the cytochrome P450 isoenzyme IID6 in the liver. The half-life
      of venlafaxine is 3-4 h and that of its principal metabolite is about 10 h. The
      daily dose of venlafaxine can be administered as either two or three divided
      doses without altering significantly the pharmacokinetics of venlafaxine. The
      most common side-effects of venlafaxine are nausea, sedation, dizziness, dry
      mouth and sweating, as well as sexual dysfunctions, primarily problems with
      erection and delayed ejaculation. In some patients, venlafaxine also causes
      sustained elevations in both systolic and diastolic blood pressure; this effect
      is dose-dependent. Venlafaxine is much safer in overdosage than the TCAs.
      Antidepressant efficacy of venlafaxine has been found both in out-patients and in
      patients. In general, its efficacy is comparable to that of comparator drugs
      (primarily TCAs or SSRIs), and in some cases even greater, and its efficacy is
      greater than that measured with placebo.

PMID- 15989563
TI  - COX-2 inhibitors at the 8th International Conference of the Inflammation Research
      Association.
AB  - An intensive search is underway for novel selective inhibitors of cyclo-oxygenase
      (COX)-2. These compounds promise to be potent anti-inflammatory agents with
      little gastrointestinal intolerance. Meloxicam, with some selectivity for COX-2,
      is already marketed, and at least two companies are carrying out clinical studies
      with selective inhibitors. A variety of potential successor compounds were
      presented at the 8th International Conference of the Inflammation Research
      Association (IRA) in Hershey, PA on 27-31 October 1996.

PMID- 15989564
TI  - Subtypes of muscarinic receptors: the seventh international symposium.
AB  - This meeting, sponsored by Boston University School of Medicine and Johann
      Wolfgang Goethe University, was co-ordinated by Dr R Levine (Boston University
      School of Medicine) and a scientific committee composed of Drs N Birdsall
      (National Institute of Medical Research), D Brown (University College London), A
      Giachetti (A Menarini), E Mutschler (Johann Wolfgang Goethe University) and N
      Nathanson (University of Washington). The meeting format consisted of both formal
      and poster presentations and a workshop, and was attended by over 200
      participants from industry and academia. The initial sessions covered muscarinic
      M1, M2 and M3 receptors, while later sessions covered the comparative aspects and
      functional interactions of these subtypes.

PMID- 15989565
TI  - 69th scientific sessions of the American Heart Association.
AB  - Out of more than 12,000 abstract submissions, 4359 were selected for presentation
      at the 69th Scientific Sessions of the American Heart Association, held in New
      Orleans, Louisiana, USA. The abstracts have been published in a supplement to
      Circulation (Volume 94, Number 8).

PMID- 15989566
TI  - The therapeutic potential of novel anticoagulants.
AB  - Conventional anticoagulant therapy has been based on indirect inhibition of
      coagulation factors with heparin and warfarin. These agents display liabilities
      prompting the development of new anticoagulants over the last two decades. The
      first to be developed was a series of low molecular weight heparins(LMWHs). Their
      favourable pharmacokinetic profiles and risk/benefit ratios led to widespread use
      in Europe and, more recently, approval for their use in the USA. Paralleling the
      development of LMWHs has been the pursuit of a different strategy focused on
      direct rather than indirect inhibition of enzymes in the coagulation cascade. In
      contrast to heparin, LMWHs, or other glycosaminoglycans, direct inhibitors exert
      their effects independent of either antithrombin III (ATIII) or heparin cofactor
      II (HCII) and more effectively inhibit clot-bound thrombin or FXa. Highly potent,
      selective (versus other serine proteases)direct thrombin and FXa inhibitors have
      been identified and isolated from natural sources, such as leeches, ticks and
      hookworms. The recombinant forms and analogues of the senatural proteins have
      been produced using molecular biology techniques, i.e., rHirudin, Hirulogs,
      recombinant tick anticoagulant peptide (rTAP), recombinant antistasin (rATS) and
      recombinant nematode anticoagulant peptide-5 (rNAP-5). The design of novel
      structures or the modification of existing chemicals has led to the synthesis of
      many non-peptide, low molecular weight inhibitors of thrombin and FXa. Some of
      them are orally active and may be suitable for long-term clinical use. In
      addition, considerable progress has been made in developing specific TF/VIIa
      complex inhibitors. The anticoagulation properties of the new agents are being
      characterised in experimental studies. Some of them have been advanced to large
      scale clinical trials and their effectiveness, and sometimes relative
      ineffectiveness,in arterial and venous thromboembolic disorders has been
      demonstrated. They are being tested for their potential as new antithrombotic
      agents that act via direct enzyme inhibition. Thus,the clinician should in future
      be able to target different thrombotic conditions with proven, specific
      anticoagulant interventions.

PMID- 15989567
TI  - Overview of clinical trials with glycoprotein IIb-IIIa receptor antagonists in
      the prevention and management of coronary.
AB  - Platelet aggregation is mediated by the glycoprotein IIb-IIIa receptor, a member
      of the integrin superfamily of membrane-bound adhesion molecules. In the
      activated platelet, binding to the major adhesive proteins, fibrinogen and von
      Willebrand, occurs due to a conformational change of the glycoprotein IIb-IIIa
      receptor. Glycoprotein IIb-IIIa receptor antagonists effectively block the
      binding of these adhesive proteins and thus inhibit platelet aggregation. Large
      scale clinical trials have demonstrated the benefits of these agents in patients
      undergoing percutaneous coronary angioplasty and with acute coronary syndromes
      compared to conventional antiplatelet therapy. Furthermore, trials are in
      progress in patients with acute myocardial infarction. The beneficial effects of
      these agents was first demonstrated with abciximab, a monoclonal antibody to the
      glycoprotein IIb-IIIa receptor, in patients at risk of coronary arterial
      thrombosis, and was further illustrated in trials with other IIb-IIIa receptor
      blocking agents, both with synthetic peptide and non-peptide receptor
      antagonists. This review focuses on the glycoprotein IIb-IIIa receptor
      antagonists most advanced in clinical development.

PMID- 15989568
TI  - The role of the renin angiotensin system in chronic renal disease.
AB  - End-stage renal disease (ESRD) is a costly and debilitating condition affecting
      250,000 patients in the United States. The incidence of ESRD has doubled in the
      past 10 years and is expected to continue to increase well into the next century
      as our population ages. Over the past 20 years investigative efforts have been
      focused on defining the pathophysiological basis of chronic renal disease and on
      therapeutic interventions designed to prevent its progression to renal failure.
      Several experimental models of progressive renal disease have been developed and
      used to examine potential mechanisms which may contribute to the pathophysiology
      of renal failure. Data from these studies indicate that the renin-angiotensin
      system (RAS) contributes significantly to the pathophysiology of renal disease in
      the experimental models examined. Data from clinical studies also indicates that
      the RAS contributes to the progression of renal disease in man as well. While our
      knowledge in this area is far from complete, numerous experimental and clinical
      studies have demonstrated that the blockade of the RAS has a distinct advantage
      in preventing the progression of renal insufficiency to complete renal failure.

PMID- 15989569
TI  - The antiatherogenic potential of blocking the renin-angiotensin system.
AB  - Angiotensin converting enzyme (ACE) inhibitors have proved effective in
      preventing or ameliorating clinical manifestations of atherosclerosis, such as
      myocardial infarction (MI) and heart failure. Experimental evidence demonstrates
      their anti-atherogenic potential; ACE inhibitors do not only suppress the
      formation of proatherogenic angiotensin II (AII), but also enhance the formation
      and release of anti-atherogenic nitric oxide (NO) at local tissue sites; both
      mechanisms are implicated in the suppression of neointima formation in the
      balloon-injured vessel wall. A similar anti-atherogenic potential is provided by
      the blockade of the renin-angiotensin system (RAS) at the level of the
      angiotensin type-1 (AT1) receptor. AT1 receptor antagonists do not only block the
      proatherogenic actions of AII, but also induce an enhanced formation and release
      of anti-atherogenic NO at local tissue sites. AT1 receptor antagonists may
      therefore prove as effective as ACE inhibitors in patients with manifest
      atherosclerosis.

PMID- 15989570
TI  - Recent advances in the development of haemoglobin-based blood substitutes.
AB  - The term 'blood substitute' is commonly used to describe products which can carry
      and deliver oxygen. These products are also referred to as 'oxygen carriers' or
      'oxygen therapeutics'. Blood substitutes are a new generation of oxygen
      therapeutics and their introduction will redefine treatment approaches in a wide
      range of medical and surgical practices. There are two major classes of this new
      generation of oxygen therapeutics (1) modified haemoglobin solutions, referred to
      as haemoglobin-based blood substitutes (HBBS) and (2) perfluorocarbon emulsions.
      Tremendous progress has been made in the past four years with the development of
      HBBS. In comparison, not much progress has been made in the development of
      perfluorocarbons as oxygen carriers. In the present review we have limited our
      discussion to the development of HBBS. Several types of HBBS have been developed
      and are in different phases of clinical trials. Free haemoglobin has been
      crosslinked, conjugated, polymerised or encapsulated to prevent its dissociation
      into dimers. The stability and purity of HBBS are extremely important in
      overcoming most of the significant toxicities of these products. Commercial
      manufacturers have utilised better proprietary formulations and purification
      technologies, and HBBS developed by these organisations have demonstrated safety
      in both preclinical and clinical studies. Recent research activities suggest a
      broad range of therapeutic applications for these new generation of oxygen
      therapeutics, 'blood substitutes'. The introduction of HBBS in critical care
      medicine will introduce a new approach of not only improving perfusion, but
      delivering oxygen to tissues.

PMID- 15989571
TI  - Growth factor antagonists for the treatment of diabetic vascular complications.
AB  - Diabetic vascular disease is characterised by altered vascular reactivity and
      blood flow, hyperpermeability, hyperproliferative responses, and increased
      extracellular matrix deposition in tissues that are sites of complications. These
      vascular functional and structural changes have been linked to excessive glucose
      metabolism in target organs via at least three pathophysiological mechanisms,
      including increased sorbitol (polyol) pathway activity, increased nonenzymatic
      glycation of vascular wall proteins, and increased protein kinase C (PKC)
      activity. These potential mechanisms of glucose toxicity remain the subject of
      intense scientific investigation, and therapies targeting each of them are being
      evaluated in clinical trials. It is becoming increasingly clear that excessive
      production of growth factors provides a common denominator linking these diverse
      mechanisms of glucose toxicity to the functional and structural vascular
      alterations associated with diabetes. Increased expression of vascular
      endothelial growth factor (VEGF) has been linked to increased metabolism of
      glucose via the sorbitol pathway, to nonenzymatic glycation, and to increased PKC
      activity, and appears to modulate the hyperpermeability and hyperproliferative
      responses of diabetes. Consequently, because of the unmet medical need and market
      size, numerous pharmaceutical and biotechnology companies have initiated research
      programmes evaluating growth factor antagonists as a potential therapeutic
      approach for treating complications associated with diabetic vascular disease.
      However, before growth factor antagonists can enter clinical testing, a number of
      important issues must be clarified, including the physiological effect of chronic
      growth factor inhibition, which appears to be necessary for ameliorating chronic
      vascular deterioration of diabetes, and administration routes, especially for
      protein-based therapies.

PMID- 15989572
TI  - Gene therapy for haemophilia.
AB  - Progress toward the development of a gene therapy protocol for the treatment of
      haemophilia has been substantial. Recent achievements include high level clotting
      factor expression in mice, dogs, and monkeys as well as phenotypic correction in
      both mouse and canine models of haemophilia. Studies using adenoviral vectors
      have contributed to much of the recent success. However, the repertoire of gene
      transfer vehicles being applied to the development of gene therapy strategies for
      haemophilia has expanded. In particular, encouraging data has been generated from
      studies using recombinant adeno-associated virus vectors. Progress toward human
      clinical trials has been inhibited by host immune responses to treatment which
      can limit the duration of therapy and prevent readministration. Several
      strategies have demonstrated the feasibility of circumventing host immune
      responses, but more effective, clinically applicable procedures remain to be
      developed. While direct in vivo gene therapy strategies have generated
      significant progress, the results from ex vivo strategies have not been as
      encouraging.

PMID- 15989573
TI  - New prospects for cardiovascular gene therapy.
AB  - Cardiovascular gene therapy has been hampered by the lack of suitable gene
      delivery vectors for in vivo applications. Low transduction efficiencies, lack of
      persistent transgene expression and undesirable inflammatory and immune responses
      have limited the prospects for human gene therapy in the cardiovascular system.
      New prospects for cardiovascular gene therapy are a result of recent vector
      developments, in particular with the use of adeno-associated virus (AAV) based
      vectors in the heart and peripheral vasculature.

PMID- 15989574
TI  - Novelties in the field of macrolides.
AB  - Research in the field of macrolide antibiotics has continued. The aims of
      research efforts are quite different with 14-, 15- and 16-membered ring
      macrolides. A review of 14- and 15-membered ring macrolides covering the period
      up to 1995 was published in a previous issue of this journal.

PMID- 15989575
TI  - Anticancer activity of farnesyltransferase and geranylgeranyltransferase I
      inhibitors: prospects for drug development.
AB  - Inhibition of farnesyltransferase (FTase) has been thoroughly investigated as a
      strategy to discover novel anticancer drugs because the oncoprotein Ras, requires
      farnesylation for its cancer-causing activity. Several highly potent and
      selective FTase inhibitors have been made and show excellent antitumour activity
      against human tumours in animal models without toxicity to normal cells. However,
      resistance of the most frequently mutated form of Ras, K-Ras, to FTase inhibitors
      and its alternative prenylation by geranylgeranyltransferase I (GGTase I), has
      cast doubts on whether K-Ras is the target for FTase inhibitors. This monthly
      update focuses on issues of critical importance to the further development of
      FTase inhibitors as anticancer agents. Alternative prenylation of K-Ras by GGTase
      I as a mechanism of resistance to FTase inhibitors, targets for FTase inhibitors
      other than K-Ras and the relevance of GGTase I inhibitors as antitumour agents
      will be discussed.

PMID- 15989576
TI  - Antigen-specific therapies for the treatment of multiple sclerosis: a clinical
      trial update.
AB  - Within the past year a host of antigen-specific therapies for multiple sclerosis
      (MS) progressed along the path from IND submission to FDA approval. The Immune
      Response Corporation vaccinated patients with a Vbeta6 peptide, demonstrating
      that the vaccine was immunogenic, well tolerated, and reduced the number of
      Vbeta6+ T-cells in the cerebrospinal fluid (CSF). Connetics Corp. conducted a
      Phase I/II trial on chronic progressive MS patients vaccinated with CDR2 peptides
      from TCR Vbeta55.2 and found that patients with a measurable response to the
      vaccine remained clinically stable for a year. A study at the University of
      Alberta MS Patient Care and Research Clinic demonstrated that intrathecal
      injection of a B cell/T cell epitope of myelin basic protein (MBP) decreased the
      level of antiMBP antibody, but iv. administration did not decrease the relapse
      rate. AutoImmune Inc. completed a Phase III trial of oral myelin in the spring of
      1997 which failed to show a statistical difference between those patients fed
      placebo and those fed daily capsules of myelin protein (Myoral). Three phase I
      trials of iv. myelin antigen(s) were initiated: MP4 (Alexion Pharmaceuticals,
      Inc.), a recombinant fusion of myelin basic protein and proteolipid protein;
      AG284 (Anergen, Inc.), a solubilised HLA-DR2:MBP peptide complex; and NBI-5788
      (Neurocrine Biosciences, Inc.), an altered peptide ligand of an immunodominant
      MBP T-cell epitope. Following the conclusion of a successful Phase III clinical
      trial, TEVA Pharmaceutical Industries LTD received FDA approval to market
      Copaxone (glatiramer acetate) for the treatment of relapsing-remitting MS in
      December of 1996 and launched the product in 1997. The recent preclinical
      research and clinical trial status of these antigen-specific MS therapeutics are
      summarized in this review.

PMID- 15989577
TI  - Sertindole (Serdolect): preclinical and clinical findings of a new atypical
      antipsychotic.
AB  - This review first describes the preclinical findings with sertindole, a novel
      phenyl indole derivative antipsychotic agent. Second, a summary is provided of
      the major clinical trials conducted to date. Based on these findings, sertindole
      appears to be an effective antipsychotic agent for the treatment of positive and
      negative symptoms of schizophrenia, with efficacy that is clearly superior to
      placebo. Sertindole is as effective as haloperidol, however, is much better
      tolerated with significantly fewer adverse neurologic effects across a wide
      dosage range of both drugs. Sertindole is associated with a significant mean
      prolongation of the QT and QTc intervals of 3 - 6% from baseline in placebo
      controlled studies. This potential adverse effect should be taken into account
      when treating specific patients with known risk factors for ventricular
      arrhythmias. Sertindole should prove to be a very useful addition to the
      therapeutic options available for the treatment of psychotic disorders.

PMID- 15989578
TI  - Olanzapine (Zyprexa):characteristics of a new antipsychotic.
AB  - Olanzapine is a thienobenzodiszepine antipsychotic,which exerts broad-spectrum
      receptor antagonism in the central nervous system.It demonstrates regionally
      selective dopamine antagonist activity as measured with the depolarisation block
      model and fos activation paradigm. Early in vivo imaging studies suggest a
      relatively low D2 occupancy in th striatum (69%) with a higher 5-HT2 occupancy in
      the cortex (84%) of 10 mg.Its pharmaco-kinetics are dose-proportional; Tmax is 5
      h and the elimination half-life is 31 h (range:21-54 h). Efficacy studies show
      equivalent antipsychotic efficacy to haloperidol with the possibility of superior
      efficacy on negative symptoms and depression. Motor side-effects are minimal with
      mild akathisia emerging at the highest doses; non-motor side-effects are also
      minimal. Olanzapine is a highly effective antipsychotic drug with minimal side
      effects. It will be an important new drug for treating schizophrenia.

PMID- 15989579
TI  - 10th International Conference on Antiviral Research.
AB  - The 10th Annual International Conference on Antiviral Research held in Atlanta,
      GA was attended by nearly 500 participants representing 23 countries. The next
      meeting will be held in San Diego, CA in April 1998. The web site for additional
      information is www.ISAR-ICAR.com.

PMID- 15989580
TI  - Fertilisation Promoting Peptide: a key player in male fertility/subfertility?
AB  - 'Male factor' problems contribute to subfertility in a significant proportion of
      couples. In some instances, defective sperm production has qualitative and/or
      quantitative effects on the semen profile; in others, no obvious defects can be
      detected, yet spermatozoa are non-fertilising. Recent studies have revealed that
      fertilisation promoting peptide (FPP), which is structurally related to
      thyrotrophin releasing hormone (TRH) and found in the prostate gland and seminal
      plasma of many mammals, has important biologically relevant effects on both mouse
      and human spermatozoa. In the presence of physiological concentrations of FPP,
      spermatozoa become fertile more quickly and are then inhibited from undergoing
      spontaneous acrosome loss, a step that would render them non-fertilising. In
      vivo, these responses could be extremely important in maximising fertilising
      potential of the few spermatozoa that reach the site of fertilisation. Prostatic
      dysfunction results in decreased production of FPP and increased production of
      less bioactive FPP-related peptides. A putative receptor (TCP-11) for FPP has
      been identified in the mouse; the gene (with a human homologue) which codes for
      TCP-11 resides within a complex known to contain genes affecting male fertility.
      These results strongly suggest that FPP plays an important role in normal
      fertility and that it might therefore provide both new therapeutic approaches for
      some cases of unexplained infertility and new approaches for male contraception.

PMID- 15989581
TI  - The role of phosphodiesterase inhibitors in impotence.
AB  - Penile erection is mediated by nitric oxide (NO) and its second messenger cyclic
      guanosine monophosphate (cGMP). The activity of cGMP is modulated by the enzyme
      phosphodiesterase (PDE). The most important physiological isoform of the enzyme
      in the penis is PDE5. Sildenafil is a specific inhibitor of this enzyme which
      potentiates nitrergic cavernosal relaxation in vitro and in animals. Clinical
      studies suggest that it is effective in the treatment of male erectile
      dysfunction (MED), which would make it the first orally active therapy for this
      condition.

PMID- 15989582
TI  - Beta3-adrenergic agonists: potential therapeutics for obesity.
AB  - During the last decade a number of beta3-adrenergic receptor agonists have been
      advanced to clinical trials. The results of human studies to date have been
      disappointing with respect to sustained increases in metabolic rate and weight
      loss. Cloning of beta3-adrenoceptors in a number of species and subsequent
      pharmacological evaluations revealed these early investigational drugs to be
      weakly active against the human receptor, suggesting an explanation for the poor
      performance of these compounds in clinical trials. This information has been
      integrated into subsequent research efforts resulting in the discovery of agents
      with activities optimised for the human receptor. This new generation of
      compounds is in late preclinical/early clinical development and are poised to
      address the role beta3-adrenoceptor signalling plays in the obese state. Issues
      related to the potential for beta3-adrenergic agonists to positively impact
      metabolic parameters in humans are also discussed.

PMID- 15989583
TI  - Neuropeptide Y receptor antagonists in obesity.
AB  - Neuropeptide Y (NPY) is a 36 amino acid amidated peptide with high sequence
      homology to the endocrine peptides, peptide YY (PYY) and pancreatic polypeptide
      (PP). They appear to interact with a family of receptors that possess high
      affinity for one or more of these peptides. Five members of the receptor family
      have been cloned, with several additional members postulated through
      pharmacological evidence. All are members of the seven transmembrane domain-G
      protein coupled receptor family. The Y1 receptor is the best characterised, with
      several nonpeptide antagonists available. This receptor appears to mediate a
      constriction of the peripheral vasculature and the 'anxiolytic' effects of
      centrally administered NPY. Less is known about the other receptors in the
      family. The Y2 receptor is believed to be presynaptic and mediates a reduction in
      neurotransmitter release. The Y4 receptor appears to be the receptor for
      pancreatic polypeptide, with high amounts of mRNA for this receptor found in the
      periphery, but lower levels in the brain. The Y5 receptor is expressed in the
      hypothalamus and has been postulated to be the receptor which mediates the
      increased food consumption seen following centrally administered NPY. Finally,
      the Y6 receptor has been cloned in the mouse and other species, but does not
      appear to encode a functional gene product in humans. Several types of nonpeptide
      Y1 and a series of Y5 antagonists have been described in the patent literature,
      though these compounds have limitations that will confine their use to
      preclinical studies. Nevertheless, considerable progress has been made in
      understanding the role of NPY and its receptors in experimental obesity. The next
      step will be the discovery of potent and selective nonpeptide antagonists, to add
      further credence to the therapeutic potential.

PMID- 15989584
TI  - Small molecule mimetics of GHRP-6.
AB  - In 1981, Bowers reported that xenobiotic peptides, derived from the Leu- and Met-
      enkephalins, demonstrated novel growth hormone (GH) secretory activity. The most
      potent peptide reported, GH releasing peptide-6 (GHRP-6), was shown to release GH
      by a different pathway to the known signalling peptide, growth hormone releasing
      hormone (GHRH). The discovery of a peptidyl GH secretagogue laid the foundation
      for the search for smaller, orally active mimetics of GHRP-6, as well as for its
      mechanism of action. This review focuses on the recent developments in the field
      of small molecule GH secretagogues from a medicinal chemistry perspective, and
      discusses various structural classes of mimetics recently reported in the
      literature.

PMID- 15989585
TI  - Dual topoisomerase I/II poisons as anticancer drugs.
AB  - Topoisomerases I and II, intranuclear enzymes that play vital roles in DNA
      replication and transcription, are attractive targets for cancer chemotherapy.
      Topoisomerase-active drugs either inhibit the ability of the enzymes to initially
      cleave DNA (catalytic inhibitors) or stabilise the fragile and normally transient
      'cleavable complexes' they form by preventing strand religation (poisons). Many
      clinically useful drugs exert their cytotoxic effects through poisoning of either
      topo I or topo II. Because the level and time-course of expression of these
      enzymes vary in different cell types, and the development of resistance to one
      type of inhibitor is often accompanied by a concomitant rise in the level of the
      other enzyme, there is an increasing interest in drugs that can act as dual topo
      I/II poisons. The major classes of such dual poisons are benzophenanthridine
      alkaloids, indolocarbazoles and lipophilic bis(naphthalimides), but include
      anthraquinones, pyridoindoles, indenoquinolones and acridines. No overall
      structure-activity relationships are discernible for this property, but small
      structural changes within a particular series appear to markedly alter the
      relative activities of analogues towards the two enzymes. This observation
      supports the 'drug stacking' model of interaction, where inhibitors with a 'deep
      intercalation mode' are responsible for topo I-mediated cleavage and those with
      an 'outside binding mode' are responsible for topo II-mediated cleavage.

PMID- 15989586
TI  - Docetaxel: a new active agent in the therapy of metastatic breast cancer.
AB  - Breast cancer is the most common malignancy in women, accounting for about 18% of
      female cancers, and over half a million new cases are diagnosed worldwide each
      year. Its incidence increases with age and is currently rising. Although the
      increased availability of screening programs has allowed earlier detection and
      treatment of primary breast cancers, many patients relapse with metastases after
      apparently successful treatment of their primary tumor and over 15,000 women in
      the UK and about 50,000 in the USA die from advanced disease each year. The
      natural course of breast cancer is very variable even after the development of
      metastases, and depends on a variety of tumor characteristics and prognostic
      factors. This is reflected in the large number of treatments currently employed.
      However, despite this wide choice and considerable research over the years,
      treatment of metastatic breast cancer (MBC) prolongs average survival times only
      slightly. Current therapy is aimed at achieving a balance between producing
      maximal tumor shrinkage to produce the most effective possible palliation of
      symptoms, and minimizing adverse effects. Anticancer chemotherapy is the
      preferred option in patients who do not respond to hormones, those with hormone
      independent tumors, those with aggressive breast cancer subtypes. A variety of
      anticancer chemotherapy regimens, using both single and combined agents, have
      been shown to be effective in achieving tumor regression in MBC. Anthracyclines
      (doxorubicin, epirubicin) are the most active of the established monotherapies,
      typically producing response rates of 50-60% during initial (first-line)
      treatment for metastatic disease, but being effective in fewer than 25% of
      patients requiring second-line therapy. The drawbacks of anthracyclines include
      dose-limiting cumulative cardiotoxicity and the development of resistant tumor
      clones after the use of anthracyclines for adjuvant or first-line therapy,
      especially if subsequent courses are required within a year. The success of these
      established chemotherapeutic agents depends greatly on the number and location of
      metastatic sites. Lymph node and soft tissue secondaries tend to respond well,
      while visceral metastases (especially in the liver) carry a particularly poor
      prognosis despite treatment. The outlook for patients with metastases involving
      more than two organ systems is also bleak. Although some patients can live for
      years with metastatic disease, the average survival time in patients with MBC is
      18-24 months, while in those with liver metastases, life expectancy averages only
      6 months. High-dose anticancer chemotherapy with granulocyte-colony stimulating
      factor (G-CSF) or autologous bone marrow transplantation has allowed the dose
      intensity of anthracyclines to be increased, and has improved the response rate
      to about 70% in selected patients with MBC. However, this approach has not been
      proven to improve survival, involves the risk of greater toxicity and drug
      related mortality, and patients with reduced clearance of anthracyclines due to
      hepatic dysfunction from liver metastases may not be suitable candidates. A
      number of new anticancer agents have also recently been introduced in an attempt
      to improve on the performance and avoid the tolerability problems associated with
      anthracyclines. Among these, antitubulin agents (taxoids and vinorelbine) have
      shown highly promising activity in MBC. This paper reviews the preclinical, phase
      I and phase II data for one taxoid, docetaxel. Docetaxel (Taxotere) belongs to
      the taxoid class of cytotoxic agents, the development of which began more than 20
      years ago. In 1971, paclitaxel (Taxol) was identified as the active compound of
      the crude extract of the bark of the Pacific Yew tree Taxus brevifolia. However,
      at that time the development of paclitaxel was hampered because of the limited
      source of the drug and difficulties with isolation, extraction and formulation.
      The second active taxoid, docetaxel, was isolated by Potier et al. in 1986.
      Docetaxel is prepared from a non-cytotoxic precursor, extracted from the needles
      of the European Yew tree Taxus baccata, that is condensed with a chemically
      synthesized side-chain. As the docetaxel precursor is freely available because of
      the regenerating capacity of the needles the development of docetaxel has thus
      been rapid.

PMID- 15989587
TI  - AL-3789: a novel ophthalmic angiostatic steroid.
AB  - Ocular neovascular diseases are a leading cause of blindness in the world.
      Research is beginning to unravel the complex mechanisms involved in the
      pathogenesis of ocular neovascular diseases, but currently there are very few
      methods for the effective treatment of these blinding disorders. AL-3789 (Alcon
      Laboratories) is an angiostatic steroid which shows significant activity in
      inhibiting new blood vessel formation in a wide variety of models of
      neovascularisation, including neovascularisation in ocular tissues. This
      angiostatic steroid has broad angiostatic activity and is effective in a number
      of different animal species and tissues, regardless of the angiogenic stimulus.
      AL-3789 is devoid of conventional steroid hormone activity and does not appear to
      have any other pharmacological side-effects at the doses and routes of
      administration tested. In preclinical safety studies, AL-3789 has no apparent
      ocular or systemic toxicity when dosed chronically by topical ocular, or by
      systemic administration and therefore it appears to be a relatively safe
      compound.

PMID- 15989588
TI  - Interleukin-16 for the gene therapy of HIV infection.
AB  - Interleukin 16 (IL-16) has been shown to function as chemoattractant factor, as a
      modulator of T-cell activation and as an inhibitor of human immunodeficiency
      virus (HIV) replication. It is now clear that IL-16 is synthesised as a large
      precursor molecule (pro-IL-16), from which as yet unidentified proteases release
      a bioactive carboxyterminal fragment. The mechanism for IL-16 secretion is still
      unknown, but it is likely that the secreted protein is smaller than the
      originally published 130 amino acids. Upon transfection of an IL-16 cDNA, human T
      cells became virtually resistant against HIV infection. This system may well be
      helpful in studying the mechanism of HIV suppression by this lymphokine. In
      addition, this approach could potentially be important for the development of
      gene therapy against HIV.

PMID- 15989589
TI  - The local anaesthetic activity of levobupivacaine does not differ from racemic
      bupivacaine (Marcain): first clinical evidence.
AB  - The local anaesthetic efficacy of levobupivacaine was compared with racemic
      bupivacaine (Marcain) in healthy male volunteers who were undergoing ulnar nerve
      blockade. Levobupivacaine, like racemic bupivacaine, produced blockade of nerve
      function with evidence of a dose response relationship for levobupivacaine. There
      were no statistically significant differences with respect to duration of sensory
      pain, sensory touch or motor block when the adjusted mean for the levobupivacaine
      groups (0.125, 0.25 and 0.5%) were compared with the 0.25% racemic bupivacaine
      control group. It is concluded that levobupivacaine is an effective local
      anaesthetic in humans with a dose-related duration of effect. Its local
      anaesthetic effect did not differ from that of racemic bupivacaine.

PMID- 15989590
TI  - Drug delivery across the skin.
AB  - Since the introduction of the first through the skin (TTS) therapeutic in 1980, a
      total of 34 TTS products have been marketed and numerous drugs have been tested
      by more than 50 commercial organisations for their suitability for TTS delivery.
      Most of the agents which have been tested have had low molecular weights, due to
      the impermeability of the skin barrier. This barrier resides in the outermost
      skin layer, the stratum corneum. It is mechanical, anatomical, as well as
      chemical in nature; laterally overlapping cell multi-layers are sealed by tightly
      packed, intercellular, lipid multi-lamellae. Chemical skin permeation enhancers
      increase the transport across the barrier by partly solubilising or extracting
      the skin lipids and by creating hydrophobic pores. This is often irritating and
      not always well-tolerated. The TTS approach allows drugs (< 400 kDa in size) to
      permeate through the resulting pores in the skin, with a short lag-time and
      subsequent steady-state period. Drug bioavailability for TTS delivery is
      typically below 50%, avoiding the first pass effect. Wider, hydrophilic channels
      can be generated by skin poration, with the aid of a small electrical current (>
      0.4 mA/cm2) across the skin (iontophoresis) or therapeutic ultrasound (few W/cm2;
      sonoporation). High-voltage (> 150 V, electroporation) widens the pores even more
      and often irreversibly. These standard poration methods require experience and
      equipment and are therefore, not practical; at best, charged/small molecules (<
      or = 4000 kDa in size) can be delivered efficiently across the skin. In spite of
      the potential harm of gadget-driven skin poration, this method is used to deliver
      molecules which conventional TTS patches are unable to deliver, especially
      polypeptides. Lipid-based drug carriers (liposomes, niosomes, nanoparticle
      microemulsions, etc.) were proposed as alternative, low-risk delivery vehicles.
      Such suspensions provide an improved drug reservoir on the skin, but the
      aggregates remain confined to the surface. Conventional carrier suspensions
      increase skin hydration and/or behave as skin permeation enhancers. The recently
      developed carriers; Transferomes, comprise pharmaceutically-acceptable,
      established compounds and are thought to penetrate the skin barrier along the
      naturally occurring transcutaneous moisture gradient. Transfersomes are believed
      to penetrate the hydrophilic (virtual) channels in the skin and widen the former
      after non-occlusive administration. Both small and large hydrophobic and
      hydrophilic molecules are deliverable across the stratum after conjugation with
      Transfersomes. Drug distribution after transdermal delivery probably proceeds via
      the lymph. This results in quasi-zero order kinetics with significant systemic
      drug levels reached after a lag-time of up to a few hours. The relative
      efficiency of TTS drug delivery with Transfersomes is typically above 50 %; with
      the added possibility of regional drug targeting.

PMID- 15989591
TI  - Clinical trials report on ongoing trials in lung cancer.
AB  - This review summarises major studies that are underway in the treatment of lung
      cancer in the world. A large number of small Phase I and II trials are being
      performed, in particular including new cytotoxic agents. This review focuses on
      randomised Phase III trials, and those mainly conducted by large co-operative
      groups.

PMID- 15989592
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
AB  - Over 10,000 research scientists attended the ICAAC meeting in Toronto, Canada.
      The continued increase in the rate of resistance in bacteria and fungi and the
      underlying mechanisms of resistance were the focus of many presentations this
      year. So, too, were the attempts to combat this emerging resistance crisis. Many
      papers described new modifications to older antimicrobials, novel classes of
      antimicrobials and the potential use of new antibacterial and antifungal targets.

PMID- 15989593
TI  - To sequence or not to sequence?
AB  - There is now incontrovertible evidence that a combination of two nucleoside
      analogues is superior to AZT monotherapy for the treatment of HIV infection.
      There is also evidence that a range of antiretroviral combinations can produce
      profound drops in plasma HIV viral load, often below the detectable limits of the
      assay. A lower rate of viral replication is associated with delays in the
      selection of viral mutants resistant to drugs; the principal reason for
      therapeutic failure. These highly effective combinations are likely to delay
      clinical events and considerably improve the prognosis in HIV-infected
      individuals. Using mathematical modelling techniques to assess the half-life of
      plasma virus infectious cells and proviral DNA, one group has gone so far as to
      suggest it may be possible to stop therapy after several years, as the virus will
      have been eliminated. More sanguine investigators, however, believe that this is
      unlikely, as some infected cellular compartments may have long half-lives and the
      virus may persist, or even continue to replicate slowly, in sanctuary sites, such
      as the CNS and genital tract, poorly penetrated by drugs. Thus, some virologists
      and clinicians believe that it is crucially important to give initial therapy
      with the strongest possible combination of drugs to achieve an 'undetectable'
      plasma viral load and that, providing compliance is good, this will lead to a
      prolonged therapeutic effect. In these circumstances no sequencing issues arise.
      Others, however, continue to believe that, in due course, the virus is likely to
      evade drug pressure. In these circumstances, consideration of a sequence of
      drugs, to avoid initial and subsequent therapy from squandering future therapy
      options through, principally, cross-resistance, becomes an important issue. None
      of the issues discussed in this review has been tested by controlled clinical
      trials but they generate hypotheses requiring urgent evaluation.

PMID- 15989594
TI  - Macrolide antibiotics in food-animal health.
AB  - Several 14- and 16-membered-ring macrolide antibiotics have acquired important
      roles in the modern production of food animals. Macrolide antibiotics exhibit
      many similar antimicrobial properties whether used in veterinary or human
      medicine. In addition to their direct inhibitory action on micro-organisms,
      macrolides exert a variety of subinhibitory concentration (sub-MIC) effects that
      are being increasingly recognised as important factors in the explanation of
      therapeutic results. Macrolides achieve wide tissue distribution and high
      intracellular concentrations that contribute prominently to their efficacy.
      Another important factor governing efficacy is the complex interaction between
      macrolides, micro-organisms, and phagocytes that may enable the host defence
      system to enhance the antibiotic's inhibitory action. A potential role for
      macrolides in modulating inflammatory processes has also been recognised. In both
      sub-MIC effects and interactions with the host immune system, different
      macrolides exert different responses that may reinforce or oppose each other.
      This complexity of responses requires additional studies in appropriate disease
      states and animal species in order to elucidate a more comprehensive
      understanding and explanation of in vivo outcomes.

PMID- 15989595
TI  - Treatment of Acinetobacter infections.
AB  - Gram-negative non-fermentative aerobic bacilli are becoming increasingly more
      involved in nosocomial infections. It has generally been recognised that the
      members of the Acinetobacter genus are among the most common agents responsible
      for severe hospital infections; their clinical importance has increased due to
      the development of antibacterial resistance mechanisms by these organisms. Over
      the last two decades the antibacterial armamentarium has progressed significantly
      and newer broad spectrum antibiotics have been used during therapy of hospital
      infections due to drug-resistant Acinetobacter spp. Despite various mechanisms of
      resistance to beta-lactams, aminoglycosides, fluoroquinolones developed by these
      organisms, the control of Acinetobacter infections can be effected by the use of
      several antibiotic combinations in 'conventional' antibiotic therapy. Recent
      surveys have pointed out the importance of using combinations of 2-amino-5
      thiazolyl cephalosporins, or imipenem with aminoglycosides, or alpha-carboxy-
      penicillins (ticarcillin) combined with beta-lactamase inhibitors. Amongst the
      latter drugs, the place of sulbactam should be redefined thanks to its intrinsic
      activity against the Acinetobacter species, associated with its inhibitory power
      against beta-lactamases. The fluoroquinolones were initially very active against
      Acinetobacter infections, but resistance to this major class of drugs has
      occurred very rapidly. However, newer compounds of this class with increased anti
      Acinetobacter activities can be used in combinations with beta-lactams or
      aminoglycosides. The potential role of rifampicin is still underestimated for the
      treatment of Acinetobacter infections despite promising in vitro activity. Novel
      derivatives of cephalosporins, carbapenems, fluoroquinolones, or completely new
      antibiotic classes, of which several investigational drugs seem promising, may
      constitute the future of antibiotic therapy and hence the treatment of
      Acinetobacter infections.

PMID- 15989596
TI  - Recent developments in pradimicin-benanomicin and triazole antibiotics.
AB  - Fungal infections are on the rise as the number of patients with compromised
      immune systems continues to increase. The need for safer and more effective
      antifungals has resulted in the search for novel drug classes and for
      modifications to existing classes, with the aim of enhancing their antifungal
      spectra and potency. In this review, two classes of antifungals are discussed:
      the pradimicin-benanomicin antibiotics and the newer triazole derivatives. These
      have activity against Candida spp., Cryptococcus neoformans and Aspergillus spp.,
      as well as variable activity against other less commonly encountered fungi
      including Pneumocystis carinii. Pradimicins-benanomicins are generally
      fungicidal, whereas the newer azoles appear to be selectively fungicidal to
      Cryptococcus neoformans and Aspergillus spp. Pradimicin-benanomicin acts by
      binding to mannan and alters membrane integrity. One water-soluble pradimicin
      candidate, BMS-181184, has been selected for clinical development. The triazoles
      act by inhibiting cytochrome P450 sterol 14a-demethylase. Four triazoles either
      currently in clinical development (voriconazole and D0870) or being considered as
      clinical candidates (ER-30346 and Sch 56592) will be discussed. The antifungal
      spectra, pharmacokinetic and toxicologic data in animals, and efficacy results in
      experimental infection models will be reviewed for BMS-181184 and the four newer
      triazoles. Results from the early clinical trials for voriconazole and D0870 will
      also be discussed.

PMID- 15989597
TI  - Antifungals targeted to the cell wall.
AB  - Serious fungal infections are increasingly common in immunocompromised patients
      and existing antifungals do not completely satisfy the medical need. The latter
      have either considerable toxicity, e.g., amphotericin, which is, however, less
      toxic in lipid formulations, or have limited activity, e.g., azoles. Cell wall
      acting antifungals are inherently selective and fungicidal; two classes of
      compounds--nikkomycin Z targeted at chitin synthase, and echinocandin LY 303366
      and pneumocandin L-743,872 targeted at alpha-1,3-glucan synthase--are currently
      in clinical development.

PMID- 15989598
TI  - Oxazolidinone antibacterial agents: development of the clinical candidates
      eperezolid and linezolid.
AB  - Antimicrobial resistance is a significant nosocomial problem and is of increasing
      importance in community-acquired infections. One approach for overcoming
      resistance is the discovery and development of agents with new mechanisms of
      action. The oxazolidinones make up a relatively new class of antimicrobial agents
      which possess a unique mechanism of bacterial protein synthesis inhibition.
      Eperezolid and linezolid are two novel analogues that have demonstrated a variety
      of positive attributes. These agents inhibit many clinically-significant
      bacterial species both in vitro and in animal models of human infection.
      Furthermore they have oral bioavailability, and are well tolerated in humans at
      doses which produce plasma concentrations in excess of the levels predicted to be
      necessary for efficacy. In this review, we discuss the key information from the
      literature that supports the Phase II development of linezolid.

PMID- 15989599
TI  - Meta-analysis and investigation of anti-infective therapies.
AB  - Meta-analysis offers an alternative approach to examining specific sub-groups,
      such as classes of antibiotics, types of bacteria as well as patient groups whose
      response to the agent under investigation may not be equivalent. In this review,
      the strengths and pitfalls of meta-analyses of anti-infective therapies will be
      discussed.

PMID- 15989600
TI  - The development of antibody delivery systems to target cancer with highly potent
      maytansinoids.
AB  - Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour
      reactive monoclonal antibodies may lead to novel, more potent agents for cancer
      therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro
      than current clinical anticancer drugs. We recently demonstrated that conjugation
      of maytansinoid drugs to monoclonal antibodies renders them highly efficacious
      against cancers of breast and colon in both in vitro and in in vivo tumour
      models. Antibody-maytansinoids represent a new generation of immunoconjugates
      that may yet fulfil the promise of effective cancer therapy through antibody
      targeting of cytotoxic agents.

PMID- 15989601
TI  - Valaciclovir: development, clinical utility and potential.
AB  - Valaciclovir (Valtrex, Zelitrex), the L-valine ester of aciclovir, increases
      aciclovir bioavailability by 3- to 5-fold over that achievable with oral
      aciclovir. It addresses many unmet needs of currently available anti-herpesvirus
      therapies. Valaciclovir extends the efficacy of aciclovir in the treatment of
      herpes zoster and genital HSV infections, using less frequent dose regimens but
      retaining the highly acceptable safety profile established for aciclovir. The
      potential for valaciclovir in CMV prophylaxis has now been proven, and further
      refining to identify the optimal dose regimen is ongoing. After oral
      administration, valaciclovir is rapidly absorbed and extensively converted to
      aciclovir and L-valine, the essential amino acid. The mode of action and spectrum
      of antiviral activity of valaciclovir are thus identical to aciclovir. The
      bioavailability of aciclovir after valaciclovir, characterised from studies in
      healthy adult volunteers, is similar in a wide range of patient populations,
      including the elderly, those with advanced HIV disease, patients with impaired
      liver or renal function, or undergoing bone marrow transplantation. No clinically
      significant drug interactions with valaciclovir have so far been identified.
      Dosage reductions in clinical use of valaciclovir are only necessary when renal
      function is severely impaired. In controlled clinical trials in herpes zoster,
      valaciclovir (1000 mg three times daily) is superior to aciclovir in speeding the
      resolution of zoster-associated pain and post-herpetic neuralgia. It is as
      effective as aciclovir in hastening rash healing. In patients with ophthalmic
      zoster, no differences were evident between valaciclovir and aciclovir treatment
      on zoster-associated pain or the occurrence of ocular complications. The safety
      profiles of valaciclovir, aciclovir and placebo were not different in this study
      programme. In a series of controlled, randomised trials of valaciclovir,
      aciclovir and placebo for the acute treatment of genital HSV infections in
      approximately 3000 patients, twice daily valaciclovir was proven as effective as
      the standard 5 times daily aciclovir regimen in resolving the clinical signs and
      symptoms of lesional disease. Early patient-initiated valaciclovir therapy (500
      mg twice daily) of recurrent genital herpes episodes was shown significantly to
      increase the chance of prevention of vesicular or ulcerative lesions, a valuable
      clinical advantage not prospectively proven for aciclovir. When used for periods
      of up to one year, valaciclovir (500 mg once daily) effectively suppresses
      genital herpes recurrences. Long-term studies of valaciclovir for HSV
      suppression, evaluating doses of up to 1000 mg daily in approximately 3000
      patients, about 25% of whom were HIV seropositive (CD+ > 100 cells/microl),
      revealed a highly acceptable clinical tolerability profile for valaciclovir that
      did not differ from aciclovir or placebo. There were no cases resembling
      thrombotic microangiopathy in these long-term studies. The aciclovir safety
      heritage and pharmacokinetic rationale for the development of valaciclovir have
      been realised through the clinical research programmes in the zoster and HSV
      indications. Further studies in these and related areas, including CMV
      prophylaxis, are in progress and aim to expand further the clinical potential of
      valaciclovir in the future.

PMID- 15989602
TI  - Stavudine:pharmacology,clinical use and future role.
AB  - Stavudine is a nucleoside analogue reverse transcriptase inhibitor of HIV-1 and
      HIV-2 and demonstrates in vitro activity with an acceptable therapeutic index in
      a range of T-lymphocyte and haematopoietic precursor cell lines. It is additive
      or synergistic in vitro with a range of other antiretrovirals, including the
      proteinase inhibitor saquinavir, in two- and three-way combinations and is active
      against zidovudine (ZDV)-resistant virus. It exhibits excellent oral
      bioavailability, with cerebrospinal fluid (CSF)/plasma penetration. In clinical
      use, stavudine monotherapy exhibits similar antiretroviral activity to ZDV, and
      is of proven clinical benefit in ZDV-pre-treated patients. In combination with
      ddI and/or nelfinavir it results in more substantial and durable responses in
      immunological and virological markers than reported with either drug alone.
      Further data on stavudine in combination with other antiretrovirals are now
      awaited. Comparative trials in ZDV-experienced patients suggest a similar
      frequency of adverse events to that observed with ZDV. Peripheral neuropathy is
      the most common dose-limiting toxicity, with haematological and hepatic function
      disturbance being infrequent. Resistance to stavudine develops slowly in vitro
      and in vivo but may lead to co-resistance to ZDV or ddI. Stavudine will be used
      clinically as a combination agent both in initial therapy and in patients with
      prior ZDV experience.

PMID- 15989603
TI  - Creutzfeldt-Jakob disease: therapeutic strategies.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative illness which belongs
      to the group of transmissible subacute spongiform encephalopathies (TSSE). Today,
      no treatment is available for TSSE. The appearance of a new variant of CJD, which
      affects young people and could be linked to so-called ;mad cow disease', has
      stimulated researchers to develop new therapies against CJD. A few drugs have
      already been shown to delay the onset of experimental TSSE. They could contribute
      to the understanding of the pathogenic mechanisms involved in TSSE and,
      therefore, could be the basis for therapeutic strategies against CJD.

PMID- 15989604
TI  - Structure-based design in drug discovery--the application of a peptoid drug
      design strategy for the development of non-peptide neuropeptide receptor ligands.
AB  - Over the last decade the increasing availability of metabolically- stable non
      peptide antagonists targeted at neuropeptide receptors has led directly to a more
      thorough understanding of the role of neuropeptides in mammalian physiology. By
      far the majority of these non-peptide neuropeptide receptor antagonists thus far
      disclosed have been developed from leads identified from broad screening of
      company compound files or natural product collections, and may thus bear little
      obvious structural resemblance to the endogenous peptide ligand. This review will
      focus on an alternative structure-based approach to non-peptide neuropeptide
      receptor ligand design, referred to as the 'peptoid' drug design strategy, in
      which an appreciation of the structure of the neuropeptide is the key to the
      success of this approach. The development and current clinical progress of
      peptoid cholecystokinin and tachykinin receptor ligands that have thus far
      resulted from this process will be highlighted and used to exemplify the
      importance of this novel approach.

PMID- 15989605
TI  - Recent advances in the identification of alpha1- and alpha2-adrenoceptor
      subtypes: therapeutic implications.
AB  - The cloning of multiple subtypes of both alpha1- and alpha2-adrenoceptors has
      renewed interest in the therapeutic application of agents interacting with these
      receptors. Effort has primarily been directed towards the design of uroselective
      alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia
      (BPH). Evidence is accumulating for the involvement of a novel alpha1
      adrenoceptor, designated as alpha1L-adrenoceptor, in alpha1-adrenoceptor-mediated
      smooth muscle contraction in prostatic and other urogenital tissues. While
      several antagonists showing a high degree of uroselectivity in animal models have
      been identified, their clinical superiority over the currently available alpha1
      adrenoceptor antagonists has not yet been demonstrated. It is possible that the
      interaction with alpha1-adrenoceptors, as yet uncharacterised subtypes, at non
      prostatic sites contributes to the therapeutic activity of this drug class in
      BPH. The alpha1-adrenoceptor subtypes involved in the control of vascular tone
      are currently being evaluated, and the profile of interaction with the various
      alpha1-adrenoceptor subtypes may play a key role in the efficacy of
      cardiovascular drugs such as carvedilol. Alpha2-adrenoceptor agonists are now
      being employed for a variety of therapeutic applications, most involving actions
      on receptors within the central nervous system (CNS). These agents are useful in
      the treatment of hypertension, glaucoma, opiate withdrawal and attention deficit
      hyperactivity disorder (ADHD), and as analgesics and adjuncts to general
      anaesthesia. While subtype selectivity has not yet been applied to the design of
      new alpha2-adrenoceptor agonists for these applications, recent gene
      mutation/knock-out experiments have identified the alpha2-subtypes involved in
      some of these actions, and optimisation of a therapeutic profile may be possible.
      Furthermore, the design of agents combining affinities for multiple adrenoceptor
      subtypes, or the combination of a specific adrenoceptor affinity profile with
      another pharmacological action, may offer advantages over molecules selective for
      an individual adrenoceptor subtype.

PMID- 15989606
TI  - N-methyl-D-aspartate antagonists for stroke and head trauma.
AB  - The N-methyl-D-aspartate (NMDA) receptor is a ligand-gated ion channel which is
      widely distributed in the central nervous system (CNS), and which mediates most
      of the fast excitatory neuronal transmission in the CNS. As with other ligand
      gated ion channels, the NMDA receptor is a macromolecular complex which possesses
      a number of intricate regulatory sites within and around a central ion channel.
      The key regulatory components for which prototypic antagonists have been
      developed are the competitive NMDA antagonist binding site, the non-competitive
      NMDA antagonist binding site within the ion channel, and the NMDA receptor
      associated glycine antagonist site. The binding domains for each of these binding
      sites possess discrete and non-overlapping SAR with regard to the chemical series
      developed to date. The potential utility of NMDA antagonists in the treatment of
      stroke and traumatic brain injury was investigated soon after the synthesis of
      the first bioavailable NMDA antagonists. Efficacy in preclinical models was
      demonstrated with both competitive and non-competitive NMDA antagonists. However,
      preclinical testing also revealed potentially clinically-limiting side-effects
      which included phencyclidine (PCP)-like actions indicative of possible
      psychotomimetic activity, cerebral vacuolisation of limbic cortical neurones, low
      therapeutic indices relative to incapacitating motor side-effects and, in the
      case of non-competitive antagonists, hypertension. These limitations have led to
      the design of clinical trials that should define the therapeutic index for this
      type of compound in humans. Currently, the first competitive antagonist to enter
      clinical trials, selfotel, is on hold, while D-CPPene is still in development.
      The non-competitive antagonist, aptiganel, is currently in Phase III clinical
      trials and its therapeutic efficacy and index should be defined in 1997 and 1998.
      The well-defined limitations of competitive and non-competitive NMDA antagonists
      have been a key impetus in the investigation of alternative approaches to
      modulating the NMDA receptor complex. In the case of glycine site antagonists,
      these compounds have been shown in preclinical studies to be devoid of PCP-like
      actions and the neuronal vacuolisation associated with the competitive and non
      competitive NMDA antagonists. This has induced the development of a number of
      chemical series with at least three compounds currently in Phase I and II
      clinical trials. These include ACEA 1021, GV150526A and ZD9379. Clinical
      efficacies and therapeutic indices of these compounds should be defined in 1998
      and 1999. An alternative approach using a partial agonist of the glycine site (1
      aminocyclopropane-carboxylic acid, ACPC) has been halted in Phase I. Another
      approach which has led to the development of NMDA receptor antagonists, selective
      for the NMDA receptor subunits 1A/2B (NR1A/2B subtype), was the discovery in
      early studies of the neuroprotective actions of ifenprodil. Structural analogues
      include eliprodil, CP-101,606 and lubeluzole. In the cases of eliprodil and
      lubeluzole, these compounds have demonstrated neuroprotection in preclinical
      models, but they possess the extremely dangerous side-effect of increasing
      cardiac repolarisation time (i.e., increased QTc interval). The therapeutic index
      for these compounds is low. This has led to the termination of eliprodil's
      development and has limited the current dosing strategy with lubeluzole. It has
      not been disclosed if CP-101,606 possesses this dose-limiting side-effect. In
      summary, strategies for drug design and development based on our knowledge of the
      NMDA receptor complex have led to the development of a new generation of
      compounds for the treatment of stroke and traumatic brain injury, which remain to
      be evaluated in the clinic. The success of this approach will be defined in the
      next two to three years.

PMID- 15989607
TI  - Melatonin receptors: potential targets for central nervous system disorders.
AB  - The pineal hormone melatonin has become the subject of considerable speculation
      in both the scientific and lay press. Media coverage, coupled with scientific
      interest fuelled by the recent molecular cloning of a family of melatonin
      receptors, has led to a renaissance in melatonin research. While numerous
      physiological effects have been attributed to melatonin, the lack of selective
      agonists and antagonists for individual melatonin receptor subtypes has hampered
      progress towards the elucidation of the roles of these receptors. This review
      focuses on the molecular and pharmacological characterisation of melatonin
      receptors, the possible clinical utility of melatonin receptor ligands, and the
      progress towards the identification of selective ligands for these receptors.

PMID- 15989608
TI  - The therapeutic potential of anti-cytokine strategies in central nervous system
      ischaemia.
AB  - Central nervous system (CNS) ischaemia is associated with an acute inflammatory
      response which appears to potentiate CNS injury, especially following
      reperfusion. This response includes the release of inflammatory mediators,
      including the cytokines interleukin-1 (IL-1) and TNF-alpha. These trigger the
      production of additional cytokines, including IL-6, and activate leukocytes which
      infiltrate the CNS. IL-6 appears to play a central role in modulating this
      response, exhibiting both pro-inflammatory and anti-inflammatory activities.
      Preliminary clinical studies suggest that plasma levels of IL-6 are correlated
      with stroke size and functional recovery. Conversely, brain levels of cytokines
      have been demonstrated to increase following experimental ischaemia. Although
      there are at present no clinical ;anti-cytokine' treatment studies, experimental
      studies modulating cytokines have shown neuroprotection.

PMID- 15989609
TI  - Ademetionine (S-adenosylmethionine) neuropharmacology: implications for drug
      therapies in psychiatric and neurological disorders.
AB  - Ademetionine (S-adenosylmethionine; SAMe) is a ubiquitous metabolite present in
      all cells and biological fluids, and serves as a methyl donor in a multitude of
      different methylation reactions involving proteins, phospholipids, catecholamines
      and DNA. Pharmaceutical preparations of some stable salts of SAMe are available
      for parenteral and oral use in humans, and have been shown to increase plasma and
      cerebrospinal fluid SAMe concentrations. In experimental studies administration
      of SAMe is associated with increases in brain monoamine neurotransmitters and b
      adrenergic and muscarinic receptor functions. These neuropharmacological effects
      are postulated to be involved in the antidepressant activity of SAMe which has
      been confirmed in numerous controlled studies. Preliminary studies indicate that
      SAMe has therapeutic potential in the treatment of other CNS disorders including
      dementia, acquired immune deficiency syndrome (AIDS)-associated myelopathy, and
      brain ischaemia. This review will focus on recent experimental and clinical
      aspects of SAMe in the central nervous system, and the therapeutic use in
      psychiatric and neurological disorders.

PMID- 15989610
TI  - Investigational drugs for eating disorders.
AB  - Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) each
      occur in about 0.5-1.5% of the population in westernised countries, and primarily
      affect women. At present, a variety of pharmacological treatments are used in
      addition to psychotherapy, with antidepressants being most the common. Currently
      available drugs, while helpful, fall far short of desired levels of efficacy.
      Based on current knowledge about neural mechanisms that regulate feeding
      behaviour, several classes of compounds are in development to treat eating
      disorders. These include cholecystokinin (CCK) antagonists, corticotropin
      releasing hormone (CRH) antagonists, histamine-3 (H3) receptor antagonists,
      neuropeptide Y (NPY) antagonists, and a variety of serotonin uptake inhibiting
      drugs. Based on currently available effective treatments, it seems reasonable
      that the serotonin uptake inhibiting drugs might hold the greatest likelihood of
      benefit for these illnesses, but the receptor antagonists in development might
      provide substantial improvement in response rates.

PMID- 15989611
TI  - The therapeutic potential of neuropeptide Y in cardiovascular disease.
AB  - Neuropeptide Y (NPY), a widely distributed peptide neurotransmitter, is
      implicated in both the central and peripheral control of the cardiovascular
      system. Pathological changes in endogenous NPY release and receptor function may
      contribute to the development and maintenance of hypertension, myocardial
      ischaemia and cardiac failure. At least six NPY receptor subtypes are known to
      exist, and the activation of a certain number of these results in complex central
      and peripheral changes in cardiovascular function. The cloning and sequencing of
      NPY receptor subtypes has led to the possibility of developing subtype-specific
      ligands targeted at NPY receptors, and this article will consider their
      therapeutic potential in cardiovascular disease.

PMID- 15989612
TI  - New prospects for the treatment of malaria.
AB  - This update focuses on drugs for both uncomplicated and severe falciparum
      malaria. Chloroquine, long the mainstay of therapy, is no longer reliable because
      of widespread resistance, but is still attractive because of its very low cost.
      The following strategies for the future use of 4-aminoquinolines in uncomplicated
      malaria are discussed: the use of other existing 4-aminoquinolines such as
      amodiaquine, drug-induced reversal of chloroquine resistance, and the development
      of new 4-aminoquinolines with activity against resistant isolates. Pyrim-
      ethamine-sulfadoxine is now the drug of first-choice in much of Africa, but
      resistance to this antifolate combination is expected to become clinically
      apparent within the next five years. Research into the utility of novel
      antifolate combinations is described. Mefloquine and halofantrine are drugs which
      are extensively used in Southeast Asia, but are too expensive for general use in
      most African countries. The possible roles for artemisinine derivatives (alone
      and in combination with either mefloquine or benflumitol), pyronaridine and
      atovaquone-proguanil are described. The absolute importance of drug cost as a
      determinant of its utility in poorer countries is emphasised.

PMID- 15989613
TI  - The 98th Annual Meeting of the American Society for Clinical Pharmacology and
      Therapeutics.
AB  - The 98th Annual Meeting of the American Society for Clinical Pharmacology and
      Therapeutics was held on March 5-8, 1997. Over 850 researchers and clinicians pre
      registered for this meeting. Papers presented at the conference focused on new
      observations. Firstly, novel therapeutic agents were discussed, then compounds
      that represent standard therapy for a number of different disease states were
      addressed. State of the art lectures provided concise updates on the status of a
      number of different issues. The following is a summary of some of the highlights
      and presentations at the conference. This summary is divided into four sections.
      Section 1 focuses on the Public Policy Debate on the ethics and utility of the
      placebo-controlled trial. Part 2 is a summary of the current status of gene
      therapy with particular reference to cystic fibrosis treatment. Part 3 is a
      summary of data on two recently approved compounds (donepezil and zafirlukast).
      The last part of this article discusses the results of drug therapy in two
      different disease states (benign prostatic hypertrophy and migraine).

PMID- 15989614
TI  - Cardiopulmonary indications for endothelin receptor antagonists: review of recent
      efficacy trials.
AB  - Recent clinical and experimental animal trials indicate that endogenously
      produced endothelin-1 (ET-1) contributes to the abnormal systemic and pulmonary
      vascular resistance associated with congestive heart failure (CHF) and pulmonary
      hypertension (PH). In experimental CHF, the chronic blockade of ET-1 actions by
      ET receptor antagonists clearly improves haemodynamic status, and improves
      cardiac structure and survival. The latter is based on limited results. In
      experimental PH there are consistent reports of prevention and reversal of PH,
      pulmonary vascular remodelling and right ventricular hypertrophy, independent of
      the inciting mechanisms. These results in experimental animals illustrate the
      potential efficacy of the ET receptor antagonists in future clinical trials. With
      five ET receptor antagonists in clinical development, and more on the way, their
      potential will soon be realised.

PMID- 15989615
TI  - Angiotensin II receptor antagonists - antihypertensive agents.
AB  - Blockade of the renin-angiotensin system (RAS) is now recognised as an effective
      approach for the treatment of hypertension and congestive heart failure (CHF).
      Today, it is possible to antagonise the effects of angiotensin II more
      specifically by blocking its receptors using non-peptide receptor antagonists.
      These compounds, which at first were used to identify the various subtypes of
      angiotensin II receptors, are now available clinically. Some of them have
      recently been launched on the market and several others are preregistered for the
      treatment of hypertension. These new molecules are as effective as angiotensin
      converting enzyme (ACE) inhibitors at lowering blood pressure in hypertensive
      patients, and appear to have similar systemic and renal haemodynamic properties
      in patients with CHF and renal diseases. Large-scale clinical trials such as the
      LIFE, the ELITE and the RENAAL studies are now underway to investigate the long
      term benefits of one of these agents in hypertension, heart failure and Type II
      diabetic nephropathy. The major clinical advantage of AT1 receptor antagonists is
      that, in contrast to ACE inhibitors, they do not induce cough. With the more
      widespread use of AT1 receptor antagonists, two unresolved questions remains
      unanswered: what is the role of AT2 receptors? Are the unblocked effects of
      angiotensin II on AT2 receptor sites of any clinical relevance to the safety
      profile or efficacy of AT1 receptor antagonists? Another interesting question is
      whether the combination of an ACE inhibitor with an AT1 receptor antagonist is
      advantageous. Studies attempting to answer these questions are underway and will
      certainly enable researchers to define more precisely the role and the advantages
      of these new specific non-peptide AT1 receptor antagonists in the treatment of
      hypertension and heart failure.

PMID- 15989616
TI  - Calcium channel blockers in cerebral ischaemia.
AB  - Ischaemic stroke usually results from the obstruction of a major cerebral vessel
      which leads to a decrease in cerebral blood flow, and a subsequent reduction in
      ATP. This energy loss leads to impaired cellular function due to reduced ATP
      dependent processes and a disruption in ionic gradients across membranes. Under
      these conditions, there is a significant efflux of K+ from cells producing
      cellular depolarisation and the movement of extracellular calcium into cells
      through calcium channels. It is this increase in intracellular calcium that leads
      to the 'calcium toxicity' that has been associated with cerebral ischaemia.
      Increased intracellular calcium triggers the break-down of phospholipids,
      proteins and nucleic acids. This is activated by calcium-dependent
      phospholipases, proteases and endonucleases, and contributes to structural and
      functional damage of the cell membrane, which compromises cell function and
      facilitates cell death. Calcium channel blockers are used routinely to treat
      cardiovascular disease and hypertension. Although some experimental studies over
      the last decade suggest efficacy/benefit in the treatment of experimental
      ischaemic stroke, clinical data do not bear this out. This article discusses the
      role of voltage-operated calcium channel blockers in stroke, and reviews much of
      the available experimental and clinical data.

PMID- 15989617
TI  - Recent developments in the management of membranous nephropathy.
AB  - Idiopathic membranous nephropathy is one of the most commonly encountered forms
      of nephrotic syndrome in adults. The natural history of the disease, observed in
      a small sample of untreated patients, reveals that a large proportion of patients
      experience spontaneous remission, whereas approximately one third of them
      progress towards renal insufficiency, and thus require dialysis. Hence, several
      attempts to treat this condition have been investigated and several protocols,
      based on different combinations of corticosteroids and/or immunosuppressive
      agents, have been proposed. However, none of these protocols has been uniformly
      adopted by renal physicians, either because of no or limited efficacy of most of
      them, or due to the potential of short- and long-term untoward effects. In this
      review, we examine the available data on the natural course of the disease and
      the possibility of identifying clinical and laboratory characteristics that could
      help to predict the course of membranous nephropathy. We also summarise the
      results of the most relevant clinical trials, and offer an updated meta-analysis
      of treatment studies, including the latest data on cyclosporin.

PMID- 15989618
TI  - Nitric oxide-releasing non-steroidal anti-inflammatory drugs: a new generation of
      antithrombotics?
AB  - Long-term use of aspirin as an antithrombotic agent is limited by its toxicity in
      the gastrointestinal tract. Even very low doses of aspirin can markedly increase
      the risk of gastrointestinal bleeding and ulceration. Addition of a nitric oxide
      (NO)-releasing moiety to non-steroidal anti-inflammatory drugs (NSAIDs) has been
      shown to greatly reduce their ulcerogenic properties as well as their renal
      toxicity. We proposed that similar derivatisation of aspirin may yield a potent,
      gastrointestinal-sparing antithrombotic drug. Two prototype compounds (NCX-4215
      and NCX-4016; Nicox SA) have been evaluated thus far. Each shows comparable or
      better anti-aggregatory activity to aspirin while not inducing detectable gastric
      damage. Current studies are aimed at determining what the optimal balance is
      between nitric oxide release and inhibition of thromboxane synthesis to achieve
      good antithrombotic activity with low toxicity. NO-aspirin derivatives appear to
      offer great potential as gastrointestinal-sparing antithrombotic drugs.

PMID- 15989619
TI  - The status of plasminogen activator inhibitor-1 as a therapeutic target.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of
      tissue-type plasminogen activator (tPA). An increase in the plasma concentration
      of PAI-1 has been proposed as a risk factor in thrombotic disease and elevated
      PAI-1 is associated with a poor prognosis in a variety of cancers. These
      observations have led to numerous studies addressing the physiological and
      pathophysiological role of PAI-1 and to the proposal that manipulation of PAI-1
      activity presents a new therapeutic target. Recent experimental studies with anti
      PAI-1 antibodies and low molecular weight inhibitors have demonstrated efficacy
      in both arterial and venous thrombosis models. These studies have confirmed the
      potential clinical benefit of reducing PAI-1 activity. As it is now possible to
      manipulate PAI-1 activity in vivo, future studies should be aimed at confirming
      the importance of PAI-1 as a major therapeutic target.

PMID- 15989620
TI  - Transcription inhibitors in inflammation.
AB  - Advances in molecular medicine have revealed a key role for altered gene
      expression in the aetiology of many inflammatory diseases, including asthma,
      rheumatoid arthritis, inflammatory bowel disease and sepsis. Until recently,
      however, modulation of gene transcription has not been the subject of directed
      pharmaceutical research efforts. Notwithstanding, it is clear that the efficacy
      of several well-established anti-inflammatory therapeutics is mediated through
      their ability to modulate gene transcription. Understanding the mechanisms of
      action of these therapeutics and defining new gene regulatory pathways has
      stimulated a new wave of anti-inflammatory drug discovery. This update aims to
      cover our current understanding of transcription inhibitors in inflammation,
      including the mechanism of action of established therapeutics and the properties
      of new chemical entities recently described in the literature.

PMID- 15989621
TI  - Mibefradil (Ro 40-5967): the first selective T-type Ca2+ channel blocker.
AB  - Mibefradil is a novel Ca2+ antagonist acting on both L- and T-type Ca2+ channels,
      with a ten-fold selectivity for T-type Ca2+ channels. It belongs to a chemical
      class different from other Ca2+ antagonists (tetralol derivative), and binds to a
      new receptor site on the L-type Ca2+ channel, where it does not affect
      dihydropyridine (DHP) binding but appears to overlap the verapamil and
      fantofarone sites. In vitro and in vivo studies indicate that mibefradil has a
      high selectivity for the coronary vasculature over the peripheral vasculature and
      the myocardium. It has no relevant negative inotropic effects in various animal
      models, in normotensive patients, and patients with hypertension or angina
      pectoris. Instead, treatment with mibefradil slightly decreases heart rate and
      improves cardiac function. Clinical studies confirm that mibefradil is an
      effective antihypertensive and anti-ischaemic drug, which may be beneficial in
      the treatment of heart failure. Its excellent pharmacological and safety profile
      combined with high bioavailability makes it a promising new drug. Many of the
      unique pharmacological properties of mibefradil may derive from its selective
      block of T-type Ca2+ channels.

PMID- 15989622
TI  - Lifibrol: first member of a new class of lipid-lowering drugs?
AB  - Management of dyslipoproteinaemia is one of the key strategies in the prevention
      of cardiovascular disease. The major target of hypolipidaemic drugs is the
      reduction of low density lipoprotein (LDL) cholesterol. Lifibrol, a novel lipid
      lowering agent, is highly potent in reducing total cholesterol, LDL cholesterol,
      and apolipoprotein B. Its efficacy in lowering serum triglycerides,
      lipoprotein(a) and fibrinogen implies additional benefit in the prophylaxis and
      treatment of coronary heart disease. Thus, lifibrol appears to be a multivalent
      anti-atherosclerotic agent. The hypolipidaemic properties of lifibrol have been
      examined in several clinical trials and in various animal models. The mode of
      action of lifibrol involves at least three mechanisms: lifibrol enhances LDL
      catabolism by sterol-independent stimulation of LDL receptor activity, reduces
      cholesterol absorption from the intestine, and slightly decreases hepatic
      cholesterol biosynthesis. Lifibrol's lipid-lowering profile and putative mode of
      action clearly distinguish it from other classes of hypolipidaemic drugs, such as
      HMG-CoA reductase inhibitors or fibric acid derivatives. Thus, lifibrol may
      represent a new class of agents affecting lipid metabolism.

PMID- 15989623
TI  - Topotecan, an active new antineoplastic agent: review and current status.
AB  - Topotecan (Hycamtin) is a water soluble semisynthetic analogue of the alkaloid
      camptothecin which has antitumour activity in preclinical models in vitro and in
      vivo. A range of Phase I studies has been performed and a daily x 5 iv. schedule,
      which showed most promising evidence of activity, was selected for extensive
      clinical evaluation. To date, topotecan has been shown to be active in a number
      of malignancies, including metastatic ovarian cancer, recurrent small cell lung
      cancer (SCLC), non-small cell lung cancer (NSCLC), breast cancer, colorectal
      cancer and myelodysplastic syndrome. In ovarian cancer, response rates of around
      15% were identified in patients who had failed standard chemotherapy, and in a
      randomised, comparative study with paclitaxel response rates of 20% (topotecan)
      and 13% (paclitaxel) were observed. In addition, overall time to progression was
      impressive at 23 weeks (topotecan) compared with 14 weeks (paclitaxel). In
      recurrent SCLC, topotecan has shown good activity in sensitive patients with a
      response rate of 39%, although the response rate in refractory patients was
      considerably lower (7%). Median survival of all patients was 5.4 months,
      acceptable for this difficult clinical scenario. Topotecan is well-tolerated in
      the majority of patients and subjective toxicities are uncommon. The principal
      side-effect is myelosuppression, mainly neutropenia. Serious clinical sequelae
      are relatively uncommon and non-cumulative. Nonhaematological toxicities are
      generally mild and not dose-limiting. In clinical use, topotecan has exhibited
      activity in multiple tumour types, with a side-effect profile that is predictable
      and manageable. The drug is under evaluation in other tumour types and in
      combination chemotherapy regimens.

PMID- 15989624
TI  - Selective cyclooxygenase-2 inhibitors: pharmacology, clinical effects and
      therapeutic potential.
AB  - Since the discovery of a second isozyme of cyclooxygenase, COX-2, the field of
      prostaglandin and inflammation research has rapidly developed. It is becoming
      more evident that inhibition of COX-2 results in the analgesic and anti
      inflammatory actions of non-steroidal anti-inflammatory drugs (NSAIDs), and that
      inhibition of COX-1 results in the adverse side-effects seen with these
      compounds. The mechanisms causing intestinal ulceration and renal toxicity are
      being elucidated, and large scale clinical trials with a preferential COX-2
      inhibitor, meloxicam, and the first clinical results with highly selective COX-2
      inhibitors, such as MK966 and celecoxib, support a superior benefit to risk
      ratio. In addition, important new areas where COX-2 expression is elevated, such
      as colonic cancer, have been identified and a role for COX-2 has also been
      proposed in Alzheimer's disease. Inhibition of COX-2 for these indications by
      selective COX-2 inhibitors may provide effective new therapies in the future.

PMID- 15989625
TI  - Anti-oxidant therapy: does it have a role in the treatment of human disease?
AB  - Free radical oxidative stress has been implicated in the pathogenesis of a
      variety of human diseases. Natural anti-oxidant defences have also been found to
      be defective in many of the same diseases. Many researchers have concluded that,
      if the imbalance between the oxidative stresses and anti-oxidant defence can be
      corrected by supplementing natural anti-oxidant defences, it may be possible to
      prevent or retard disease progression. Potential anti-oxidant therapies include
      natural anti-oxidant enzymes and vitamins or synthetic agents with anti-oxidant
      activity. Diseases where anti-oxidant therapy may be beneficial can be divided
      into those involving acute intervention, such as reperfusion injury or
      inflammation, and those involving chronic preventative therapy, such as
      atherosclerosis, carcinogenesis and diabetic vascular disease. The pharmaceutical
      considerations are different in each case. The principles guiding the
      development, use and assessment of anti-oxidant therapies are discussed in this
      review.

PMID- 15989626
TI  - The therapeutic potential of interleukin-6 hyperagonists and antagonists.
AB  - Interleukin-6 (IL-6) is a 4-helical protein that binds to a specific IL-6
      receptor on target cells and to two molecules of the promiscuous signal
      transducing protein, glycoprotein 130 (gp130). Structure-function analysis has
      led to the definition of molecular contacts between IL-6 and its receptor
      subunits. This knowledge has led to the design of competitive antagonistic
      proteins that retain their receptor binding capability, but fail to stimulate one
      or both gp130 proteins; the properties of such recombinant antagonistic proteins
      are compared with traditional neutralising monoclonal antibodies targeted at IL-6
      or receptor subunits. Furthermore, several strategies have been employed to
      construct molecules with increased bioactivity. Possible therapeutic applications
      in putative IL-6 dependent haematologic disorders, e.g., Castleman's disease
      (CD), POEMS syndrome, multiple myeloma, and bone diseases, e.g., Paget's disease,
      osteoporosis, are outlined. IL-6 antagonists could also, in theory, suppress
      inflammatory activity in rheumatic and autoimmune diseases and could prevent
      secondary amyloidosis. This principle may prove advantageous in myocardial
      infarction (MI) and unstable angina pectoris. More generally, IL-6 antagonists
      could improve the wasting and microcytic anaemia of chronic diseases. IL-6
      antagonists might slow down development of mesangio-proliferative
      glomerulonephritis (MPGN). Hyperagonistic variants of IL-6 have a potential use
      in the ex vivo expansion of haematopoietic progenitor cells and as thrombopoietic
      agents. They might well be the first drugs to aid liver regeneration in vivo.

PMID- 15989627
TI  - Melanoma vaccines: prospects for the treatment of melanoma.
AB  - A number of melanoma vaccines, made from whole melanoma cells or components of
      melanoma cells, are being tested in Phase II or III trials in patients after
      surgical removal of high risk primary or regional lymph node metastases, or in
      those with disseminated melanoma. During the progress of these trials, a number
      of melanoma antigens and their peptide epitopes that are recognised by human T
      cells have been described. These findings and new information about antigen
      recognition by human T-cells have made it possible to explore the use of peptide
      epitopes targeted at T-cells as melanoma vaccines. Preliminary results are
      encouraging and suggest that it may soon be possible to use well defined
      vaccines, selected on the basis of the antigenic phenotype of the patient's
      melanoma and their HLA status. Equally exciting advances have been made preparing
      and using recombinant viral vectors containing genes that code for melanoma
      antigens. Experimental studies on the use of naked DNA as vaccines are also
      proceeding. Several fundamental obstacles preventing the effective use of T-cell
      epitope vaccines remain. These include selection of HLA and tumour antigen loss
      variants by the immune system, and conditioning of an ineffective immune response
      by the growing tumour. These aspects suggest that the development of effective
      vaccine therapy in the future may require a combination of strategies designed to
      stimulate HLA-restricted and -non-restricted effector cells, and judicious use of
      cytokines to obtain an effective immune response.

PMID- 15989628
TI  - Phospholipase A2 inhibitors in development.
AB  - To date, three isoforms of phospholipase A2 (PLA2) have been identified. Of
      these, the two Ca2+-dependent isoforms, secretory (sPLA2) and cytosolic
      phospholipase A2 (cPLA2), are targets for new anti-inflammatory drugs. The
      catalytic mechanisms and functions of the third isoform, Ca2+-independent
      cytosolic phospholipase A2 (iPLA2), are unknown at present. sPLA2 and cPLA2 are
      both implicated in the release of arachidonic acid and prophlogistic lipid
      mediators. However, recent findings provide evidence that cPLA2 is the dominant
      isoform in various kinds of inflammation, such as T-cell-mediated experimental
      arthritis. A triple function of PLA2-derived lipid mediators has been suggested:
      causing immediate inflammatory signs, involvement in secondary processes, e.g.,
      superoxide free radical (O2) generation, apoptosis, or tumour necrosis factor
      alpha (TNF-alpha)-cytotoxicity, and controlling the expression and activation of
      pivotal proteins implicated in inflammation and cell development, e.g.,
      cytokines, adhesion proteins, proteinases, NF-kappaB, fos/jun/AP-1, c-Myc, or
      p21ras. In the past, research predominantly focused on the development of sPLA2
      inhibitors; however, present techniques enable discrimination of cPLA2, sPLA2,
      and iPLA2, and specific inhibitors of each of the three isoforms are likely to
      appear soon. Over the last decade, between 40 and 50 sPLA2 inhibitors have been
      described; and the list is growing. However, of these, few have the potential for
      clinical success, and those that do are predominantly active site-directed
      inhibitors, e.g., BMS-181162, LY311727, ARL-67974, FPL67047, SB-203347, Ro-23
      9358, YM-26734, and IS-741. At present, there are no likely clinical candidates
      emerging from the ranks of cPLA2 and iPLA2 inhibitors in development. Indications
      for which PLA2 inhibitors are being pursued include, sepsis, acute pancreatitis,
      inflammatory skin and bowel diseases, asthma, and rheumatoid arthritis. The three
      main obstacles to the successful development of PLA2 inhibitors include,
      insufficient oral bioavailability, low affinity for the enzyme corresponding to
      low in vivo efficacy and insufficient selectivity.

PMID- 15989629
TI  - N-alkyl-substituted glycopeptide antibiotics.
AB  - The glycopeptide antibiotic vancomycin has proved valuable in the treatment of
      staphylococcal and enterococcal infections, particularly those caused by strains
      resistant to other antibiotics. The emergence of high-level resistance to
      vancomycin within the enterococci, and its potential for transfer to other
      pathogenic Gram-positive cocci, has led to interest in developing new
      glycopeptide antibiotics with activity against vancomycin resistant organisms.
      The N-alkylated glycopeptide antibiotics, under development by Lilly Research
      Laboratories, represent a new series of compounds possessing these properties.
      The lead compound in this series, LY 333328, is reported to be in Phase I trials.

PMID- 15989630
TI  - Novelties in the field of parenteral cephem antibacterials since 1993.
AB  - There is still considerable interest in cephem antibacterial agents. In fact,
      there are a significant number of patents submitted for this antibacterial class.
      All the new cephem derivatives, independent of which group they belong to (III to
      V), possess a 2-amino-5-thiazolyl or a 5-amino-2-thiadiazolyl ring with an oxime
      group (at position 7 of the cephem nucleus). At position 3, they have a C-3'
      quaternary ammonium moiety. Research has focused on the following structural
      modifications: the nature of the oxime residues and the charged azolium
      heterocycle, and the addition of the vinylogous chain. The aim of researchers is
      to increase the overall activity of these compounds against Gram-negative
      bacilli, including against isolates producing type 1 beta-lactamases or extended
      spectrum beta-lactamases (Enterobacteriaceae). Non-fermentative Gram-negative
      bacilli are now included in the first screening process, in addition to
      Pseudomonas aeruginosa. Extensive research is ongoing with the aim of solving the
      MRSA problem. New promising entities have been reported.

PMID- 15989631
TI  - Meloxicam: a selective COX-2 inhibitor non-steroidal anti-inflammatory drug.
AB  - Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) that selectively
      inhibits the inducible isoform of the cyclo-oxygenase (COX)-2 enzyme. This enzyme
      has a major role in mediating the inflammatory response, while synthesis of
      prostaglandins required for normal physiological functioning of the stomach and
      kidneys is under the control of the constitutive isoform, COX-1. Other NSAIDs in
      clinical use show varying degrees of selectivity towards COX-1. Only meloxicam
      and (albeit to a lesser extent) nimesulide could be described as selective for
      COX-2. In comparative trials of patients with osteo- and rheumatoid arthritis,
      meloxicam has been found to be at least as effective as other NSAIDs, but with a
      greatly reduced incidence of gastrointestinal side-effects. There is no evidence
      that meloxicam causes any deterioration in renal function in patients with
      moderate degrees of renal failure, and no evidence of drug accumulation with
      continued use. Meloxicam's half-life of 20 h makes it ideal for once daily
      administration, and it is 99% converted to inactive metabolites prior to
      excretion. No clinically significant drug interactions have been detected, making
      it suitable for use in patients with co-existing pathology. Meloxicam's safety
      and tolerability make it a significant advance in the treatment of rheumatic
      disease.

PMID- 15989632
TI  - Pharmacological developments in male contraception.
AB  - To date, the current methods of male contraception are limited to condoms, coitus
      interruptus and vasectomy, all of which are beset with difficulties. The condom
      is inconvenient, dulls sensation, and although somewhat effective against
      sexually transmitted disease, has an increased failure rate over time of usage.
      Coitus interruptus reduces the pleasurable aspects of intercourse and is plagued
      with a high failure rate. Vasectomy is virtually sterilisation. The current
      research into new forms of contraception is as diverse as the mechanisms
      controlling male fertility. The majority of effort has focused on
      antispermatogenic agents. Hormonal agents that suppress spermatogenesis appear
      nearest to final development and are primarily centred around various
      testosterone esters. These can be administered alone or in combination with
      progestogens. Another promising line of study centres on gonadotropin releasing
      hormone (GnRH) antagonism resulting in suppression of gonadotropins. Non-hormonal
      antispermatogenic agents include numerous phytochemicals, and testicular enzyme
      inhibitors. Post-testicular approaches to male contraception include agents that
      interfere with sperm metabolism, motility, maturation or transport. This review
      summarises recent clinical and animal studies on these compounds with emphasis on
      their mechanism of action, advantages and drawbacks.

PMID- 15989633
TI  - Parathyroid hormone and related peptides for the treatment of postmenopausal
      osteoporosis.
AB  - Osteopenia, a skeletal condition characterised by bone loss, affects over 10% of
      the North American population, with a worldwide incidence of 200 m. In the
      absence of treatment, osteopenia usually progresses to osteoporosis,
      characterised by more severe bone loss and, ultimately, by fractures. In the US
      alone osteoporosis affects more than 25 m people, and causes more than 1.3 m
      fractures a year. This skeletal deterioration is accelerated subsequent to
      menopause and thus can affect women at a relatively young age. Treatment of
      postmenopausal osteoporosis primarily involves the use of hormones (calcitonin,
      oestrogen) or organic molecules (bisphosphonates) which are able to prevent
      skeletal loss through inhibition of osteoclastic bone resorption. While this may
      be adequate prior to significant skeletal deterioration and fractures, the
      patient who has already lost large amounts of bone, in the presence or absence of
      fractures, requires more aggressive therapy to rapidly rebuild the skeleton.
      There is now substantial evidence that parathyroid hormone (PTH) is an agent
      capable of reversing such skeletal loss characteristic of osteoporosis. Numerous
      animal studies, in conjunction with investigator-initiated clinical trials, have
      demonstrated the anabolic effects of PTH and related peptides in osteoporotic
      conditions associated with lack of oestrogen. Large, well-controlled clinical
      trials are underway to evaluate the safety and efficacy of PTH and PTH-like
      peptides in postmenopausal osteoporosis. The addition of these agents to the
      clinician's armamentarium should provide more effective treatment of this
      condition, thereby preventing the fractures and debilitation that frequently
      accompany osteoporosis.

PMID- 15989634
TI  - Insulin and lipid metabolism: new developments in drug therapy.
AB  - Current treatments for non-insulin-dependent diabetes mellitus (NIDDM) remain far
      from ideal. The presence of both hyperinsulinaemia and resistance to insulin
      action in NIDDM challenges the rationale of treatments which primarily boost
      insulin secretion. Novel therapeutic strategies focus mainly on increasing
      peripheral sensitivity to endogenous insulin, an approach which has the potential
      not only to treat, but also to prevent NIDDM in high-risk individuals. The most
      promising new agents are the thiazolidinedione derivatives, in particular
      troglitazone. Thiazolidinediones are ligands for a specific subtype of the
      peroxisome proliferator activated receptor (PPAR), and decrease plasma glucose
      levels in both obesity and NIDDM, while at the same time reducing circulating
      insulin and free fatty acid levels. The current development status of these
      agents is reviewed, along with an assessment of their potential in the prevention
      and treatment of diverse pathophysiological states characterised by insulin
      resistance, including atherosclerosis and polycystic ovarian disease. Reference
      is made to the current status of other experimental agents including hydantoin
      derivatives, (3)-adrenoceptor agonists, and inhibitors of lipolysis.

PMID- 15989635
TI  - The role of B7-2 (CD86) in tumour immunity.
AB  - Tumour cells engineered to express co-stimulatory molecules on their surface
      provide researchers with powerful new tools to manipulate antitumour responses.
      It has been demonstrated that B7-1+ and B7-2+ tumour cells can elicit effective
      responses against their wild-type counterparts. This response is primarily
      mediated by CD8+ cytolytic T-lymphocytes. The co-stimulatory ability of B7-2+
      tumour cells is comparable to that of B7-1+ tumour cells, though with some
      exceptions. However, on host antigen-presenting cells (APC), B7-2 plays a
      dominant role in inducing T-cell-mediated immune responses. Up-regulation of B7-2
      on host APC may, therefore, present an effective means of generating potent
      antitumour immunity.

PMID- 15989636
TI  - Gene-directed enzyme prodrug therapy: a review of enzyme/prodrug combinations.
AB  - Gene-directed enzyme prodrug therapy (GDEPT) is a promising, new, two-step
      treatment for cancer chemotherapy. In the first step, the gene for a foreign
      enzyme is administered and is directed to the tumour, where it is expressed by
      the use of specific promoters. In the second step, injected prodrugs are
      activated by the foreign enzyme. The design and synthesis of prodrugs able to
      undergo enzymatic activation in such systems is an essential component. This
      review focuses on the requirements which must be fulfilled by the components of
      GDEPT systems in order for this therapy to be considered a realistic possibility.
      A special emphasis is placed on the description of the prodrugs used in GDEPT
      protocols and the requirement for a bystander effect is also discussed.

PMID- 15989637
TI  - Low molecular weight heparins: a developmental perspective.
AB  - Low molecular weight heparins (LMWHs) are now universally accepted as drugs of
      choice for post-surgical prophylaxis of deep vein thrombosis (DVT). Currently
      these agents are also being developed for the treatment of thrombosis and various
      cardiovascular indications. Due to manufacturing differences, each of the LMWHs
      exhibits a distinct pharmacological and biochemical profile. The specific
      activity of these agents in the anticoagulant assays ranges from 35 - 45 anti-IIa
      U/mg, whereas the specific activity in terms of anti-Xa units is designated as 80
      - 145 anti-Xa U/mg. These LMWHs are capable of producing product-specific dose-
      and time-dependent antithrombotic effects in animal models of thrombosis. While
      the ex vivo effects are initially present at doses that are antithrombotic, these
      agents have been found to produce sustained antithrombotic effects without any
      detectable ex vivo anticoagulant actions. In experimental animal models and in
      various clinical trials, these agents have also been found to release tissue
      factor pathway inhibitor (TFPI) after both iv. and sc. administration. Repeated
      administration of LMWHs produces progressively stronger antithrombotic effects;
      however, the haemorrhagic responses vary and are largely dependent on the product
      used. The release of TFPI following iv. and sc. administration in a primate model
      also demonstrates product individuality and the relevance of this inhibitor to
      the actions of LMWHs. Furthermore, repeated administration, mimicking the post
      surgical prophylaxis of DVT, leads to product-based augmentation of the
      antithrombotic or haemorrhagic effects. Antithrombotic and haemorrhagic studies
      are discussed, comparing the pharmacological profile of some of the available
      LMWHs. Product individuality, in terms of relative potency in different assays
      and the failure of standardisation protocols to provide any guidelines for
      product substitution and prediction of the clinical effects, is also addressed.

PMID- 15989638
TI  - Alzheimer's disease and related dementias: prospects for treatment.
AB  - Alzheimer's disease (AD) represents a major challenge to healthcare costs and to
      academic and pharmaceutical research efforts. The approval in 1996 of the first
      of the second generation acetylcholinesterase inhibitors, donepexil (Aricept,
      Eisai/Pfizer), has offered new hope, albeit palliative, to AD sufferers and care
      givers. Research has continued on the genetics of AD with the identification of
      the autosomal dominant inheritance of genetic defects in one of three distinct
      genes coding for the presensilins 1 and 2 and amyloid precursor protein (APP).
      While driving an ever increasing research effort related to the production,
      deposition and clearance of Abeta peptides, these mutations account for less than
      10% of the AD cases reported, indicating that other causative factors, both
      genetic and environmental, may contribute to the pathophysiology of AD unrelated
      to familial cohorts. A newly developed transgenic mouse model and a broader
      appreciation of the multifactorial nature of this complex, chronic disease state
      may help provide a more objective approach to understanding the disease per se as
      opposed to amyloid neurotoxicity specifically which may or may not be causative.

PMID- 15989639
TI  - The therapeutic potential of neuropeptide Y in central nervous system disorders
      with special reference to pain and sympathetically maintained pain.
AB  - Neuropeptide Y (NPY), a widely distributed peptide, has been shown to have
      numerous effects in both the central and peripheral nervous systems. In
      particular, NPY has an important role in mediating analgesia and hyperalgesia by
      distinct central and peripheral mechanisms. At least six NPY receptor subtypes
      are known to exist and the development of subtype-specific ligands targeted at
      NPY receptors will offer novel therapeutic agents. This article will review the
      involvement of NPY in diverse pathologies of the nervous system, including pain,
      and will propose a role for NPY in the maintenance of sympathetically maintained
      pain.

PMID- 15989640
TI  - American Association for Cancer Research 1997: progress and new hope in the fight
      against cancer.
AB  - Considerable progress has been made with tyrosine kinase inhibitors. After long
      and sustained efforts, several tyrosine kinase inhibitors with convincing in vivo
      experimental antitumour properties such as CP-358,774, ZD 1839, CEP-751 are
      entering Phase I clinical trials. Significant in vivo experimental antitumour
      activity has also been described for two new families of farnesyl transferase
      inhibitors (SCH 59228 and PD 083176 series). Novel inhibitors of tubulin
      polymerisation are on the verge of entering clinical trials. These include
      F12458, an analogue of vinorelbine, and C52/C55 cryptophycin derivatives.

PMID- 15989641
TI  - Identification and development of novel antifibrotic agents.
AB  - The second IBC meeting on fibrosis was held in Washington DC on April 28 - 29.
      Presentations covered a broad range of topics, including investigation of basic
      mechanisms that underlie the causes of fibrosis to novel therapeutic methods.
      Although the investigative area is in an early stage, much progress has been made
      concerning the development of a uniform mechanism for fibrotic disorders. It is
      anticipated that significant gains in the understanding of the cellular and
      molecular base for these disorders will lead to the development of effective
      therapeutic approaches in the near future.

PMID- 15989642
TI  - Future therapies for rheumatoid arthritis: remedies from the horns of a dilemma?
AB  - Drugs used to treat arthritis can be broadly classified into either anti
      inflammatory or immunosuppressive/immunomodulatory agents. Non-steroidal anti
      inflammatory drugs (NSAIDs) are used for both osteoarthritis (OA) and rheumatoid
      arthritis (RA), while drugs with an immunological mechanism of action are only
      applicable to RA. The total market value for anti-arthritic drugs is estimated to
      be 8.4 bn dollars, with the OA segment worth 6.9 bn dollars. In contrast, the
      major RA markets are valued at approximately 1.5 bn dollars. Drugs currently in
      late phase development reflect the accepted approaches towards treating the
      symptoms of arthritis, or suppressing immunological mechanisms considered to be
      the driving force for the underlying disease process in RA. The size of both the
      RA and OA markets, however, creates an incentive to develop new therapeutics
      which do not conform to these two approaches, but target new molecular
      mechanisms. Compounds currently in preclinical development demonstrate that it
      may be possible to combine anti-inflammatory and slow-acting antirheumatic
      activity into a single therapeutic. This new generation of anti-arthritic
      compounds has the potential to redefine the way in which common forms of
      arthritis, mixed connective tissue diseases and musculoskeletal diseases are
      treated in the future.

PMID- 15989643
TI  - Tryptase inhibitors: a novel class of anti-inflammatory drugs.
AB  - Tryptase, a serine protease released from mast cell secretory granules, is found
      at elevated levels in pathophysiologic conditions associated with allergic
      inflammation. The in vitro and in vivo biological activities of tryptase strongly
      suggest that tryptase influences lung function, inflammation, matrix degradation,
      and tissue remodelling. The pathophysiologic role for tryptase in diseases of
      airway inflammation such as asthma has been confirmed from studies using the
      selective tryptase inhibitor APC 366 in the allergic sheep model. APC 366
      inhibited the allergen-induced early and late airway responses, blocked
      postchallenge airway hyperresponsiveness, and reduced airway inflammation. A
      pilot clinical trial with mild to moderate asthmatics also showed that APC 366
      protected against allergen-induced early and late responses and reduced airway
      hyperresponsiveness. Current data provide compelling evidence that tryptase plays
      a fundamental role in allergic inflammation, and selective tryptase inhibitors
      may represent a novel class of anti-inflammatory therapeutics for treating asthma
      and other mast cell-mediated diseases.

PMID- 15989644
TI  - Cholecystokinin-A receptor antagonists: therapies for gastrointestinal disorders.
AB  - Cholecystokinin (CCK) is a peptide that exerts several regulatory functions in
      the periphery, as well as in the brain. The biological functions attributed to
      CCK are mediated by two receptor subtypes, termed CCKA and CCKB, located
      predominantly in the gastrointestinal (GI) tract and in the brain, respectively.
      Several selective and potent non-petide CCKA receptor antagonists have been
      synthesised and fully characterised in preclinical studies. A few of them have
      been, and continue to be tested in humans. This paper focuses on the data
      available on the effect of CCKA receptor antagonist administration in humans, and
      shows how, in addition to allowing a more exact definition of the role of CCK in
      the regulation of some GI functions, these drugs may also possess therapeutic
      potential in GI disorders.

PMID- 15989645
TI  - Gene therapy for arthritis.
AB  - In the two years since arthritis gene therapy was last reviewed in this journal,
      there has been rapid progress on several fronts. Although vector development
      remains a slow process and long-term gene expression is not easily obtained, very
      encouraging preclinical data in animal models of arthritis are now emerging.
      Collectively, these demonstrate the principle that transfer of cytokine
      antagonist genes to joints has a marked anti-arthritic effect. Other options
      under active investigation are the transfer of cytotoxic genes to effect a
      surgical synovectomy, and the transfer of oligonucleotides that antagonise the
      actions of transcription factors. Two human clinical trials of gene therapy for
      rheumatoid arthritis have been initiated. There are now preliminary data
      suggesting that gene therapy may also be helpful in osteoarthritis, as well as in
      the repair of cartilage, meniscus, ligaments, tendons and bones.

PMID- 15989646
TI  - Subversion of chemokine receptors by HIV: how can we exploit this?
AB  - The recent discovery that the chemokines RANTES (regulated upon activation,
      normal T-cell-expressed and secreted), macrophage inflammatory protein-1alpha
      (MIP-1a), and macrophage inflammatory protein-1beta (MIP-1b) are important
      modulators of HIV-1 infection and the subsequent identification of the essential
      role that chemokine receptors play as co-receptors for HIV-1 infection have
      provided new insight into the pathogenesis of HIV-1. On May 10, 1996, Ed Berger's
      group of the NIH announced the identity of one of the elusive ;co-receptors' for
      HIV-1. This, and subsequent papers showing that the expression of specific seven
      transmembrane (7TM) chemokine receptors and CD4 confers susceptibility to
      infection by HIV-1, has led to rapid and exciting advances in both chemokine and
      HIV research. During the year since then, a number of elegant studies by
      different groups have identified additional co-receptors for HIV-1 and the
      receptor involved in HIV-2 infection, as well as extended our understanding of
      the mechanism HIV utilises to enter cells. A number of researchers at academic
      institutes, pharmaceutical and biotech companies are gambling that this will
      translate into new therapeutics for the treatment of HIV infection and AIDS.

PMID- 15989647
TI  - The therapeutic potential of inducing molecules.
AB  - Many fundamental developmental mechanisms that result in the generation and
      formation of specific cells and organ systems are not limited to embryogenesis.
      Regenerative processes in the adult serve to help regulate cellular turnover in
      systems where specific cell numbers or balance is crucial. In addition, these
      processes can be re-activated to replace cell populations which are lost due to
      damage or disease. Induction of differentiation of one cell type by another is
      one mechanism that also acts as a regenerative process in the adult. Molecules
      which direct these processes are termed inducing molecules and they are prevalent
      and active in many adult organ systems such as the haematopoietic, osteogenic and
      reproductive systems. To date, recombinant forms of inducing molecules identified
      in the haematopoietic system are being used clinically to stimulate production of
      specific cell types that are depleted during chemotherapy or dialysis treatments.
      The prospect that other inducing molecules for other organ systems may be as
      effective clinically has prompted intense research. The ability to harness
      inducing molecules as effective therapeutic agents to treat cell deficits in
      congenital or acquired disease states is the goal of several biotechnology
      companies.

PMID- 15989648
TI  - Schizophrenia - advances in drug therapy.
AB  - It has become increasingly clear that classical drug treatments for
      schizophrenia, while valuable for many patients, are far from optimal. Not only
      do they induce unpleasant side-effects, but they are also limited in their
      antipsychotic efficacy in a substantial proportion of patients. Using the
      uniquely effective but pharmacologically complex drug, clozapine, as a model, a
      variety of receptors in addition to the dopamine D2 site have been identified as
      targets for drug development; the 5-HT2A site has received the greatest interest
      in this respect. Several new drugs in development as antipsychotics have
      pharmacological effects at 5-HT2 and other clozapine-sensitive receptors; the
      receptor mechanisms underlying both the antipsychotic efficacy and limitations of
      these compounds are reviewed here, as are some other potential drug therapies
      that do not share clozapine's receptor pharmacology.

PMID- 15989649
TI  - Epothilones: novel microtubule-stabilising agents.
AB  - The past few years have witnessed the regulatory approvals of the anticancer
      microtubule stabilising taxane drugs, Taxol and Taxotere, which are rapidly
      gaining acceptance as important antineoplastic agents with potential against
      numerous solid tumour malignancies. Despite a basic understanding of the
      biochemical target of taxanes dating back nearly 20 years, new classes of tubulin
      binding microtubule polymerisation enhancers were only reported in the last two
      years. Epothilones and discodermolide are newly discovered compounds, which are
      structurally distinct from the taxanes, but which possess similar tubulin
      polymerising and cell biological effects. In the first studies reported, these
      compounds displayed similar or greater potencies than taxanes, and the
      epothilones may represent an advance over the taxanes in retaining toxicity
      against various taxane-resistant cell lines. This review summarises the data
      published on epothilones and discodermolide and proposes further steps that could
      establish these new classes of compounds as potential second generation
      microtubule polymerisation enhancers.

PMID- 15989650
TI  - DNA minor groove binding ligands: a new class of anticancer agents.
AB  - This paper gives an overview of the available pharmacological and clinical data
      of a new class of anticancer drugs which act by binding DNA in the minor groove,
      comprising cyclopropylpyrrolo-indole (CC-1065) derivatives and Distamycin
      derivatives. The emphasis of this review is placed on the distinctive mode of
      action of these drugs. Molecular pharmacology studies indicate that CC-1065 and
      its derivatives, and the benzoyl mustard derivative of Distamycin, Tallimustine,
      possess the most striking DNA sequence specificity of alkylation observed to date
      for an alkylating agent of relatively small molecular weight. The effects on the
      regulation of gene transcription, the perturbation of the cell cycle, and the
      mechanism involved in the repair of the DNA lesions induced by these drugs all
      strongly support the view that minor groove ligands act by a mechanism different
      from those previously described for other anticancer drugs. The CC-1065
      derivatives, Adozelesin and its prodrug, Carzelesin, and Tallimustine were found
      to be very effective against several murine tumours and human xenografts, and
      were shown to be active against experimental tumours that were resistant to other
      antineoplastic agents, including conventional alkylating agents. The clinical
      studies performed so far do not confirm in humans the remarkable antitumour
      activity observed in mice. The major reason appears to be a very high
      susceptibility of human bone marrow to both CC-1065 derivatives and Tallimustine
      as compared to mouse bone marrow, which makes it impossible to administer these
      drugs at sufficiently high doses to exert antitumour effects. The search for new
      minor groove binders, which possess a different DNA sequence specificity of
      alkylation and which are less cytotoxic for human bone marrow cells, is still in
      progress. It will be several years before it is possible to draw firm conclusions
      on the clinical effectiveness of this class of drugs.

PMID- 15989651
TI  - Pantoprazole: a new and more specific proton pump inhibitor.
AB  - Pantoprazole is the third proton pump inhibitor (PPI) to be launched for the
      treatment of acid-peptic diseases. Like other drugs in this class, pantoprazole
      causes long-lasting inhibition of acid secretion by inactivating the parietal
      cell H+/K+-ATPase. Compared with H2 antagonists, pantoprazole results in faster
      pain relief, more rapid ulcer healing, healing of resistant ulcers and far
      greater efficacy in oesophageal reflux disease. The three PPIs currently
      available display almost identical efficacy in the treatment of acid-peptic
      diseases and when included as part of Helicobacter pylori eradication regimes.
      However, pantoprazole shows improvements in selectivity and pharmacokinetic
      properties compared with omeprazole and lansoprazole. The bioavailability of
      pantoprazole is considerably higher than omeprazole, remains constant upon
      repeated dosing, and is unaffected by food. Significantly, pantoprazole does not
      influence hepatic cytochrome P450 activity and does not therefore interact with
      co-administered drugs. This is in contrast to omeprazole, which inhibits P450,
      and lansoprazole, which appears to weakly induce multiple metabolic pathways.
      Although pantoprazole is entering an antisecretory market dominated by omeprazole
      and ranitidine, it has a number of potential advantages. In this respect it is
      worth recalling that enhanced specificity and the absence of drug interactions
      were decisive factors in determining market share in the H2 antagonist era.
      Pantoprazole may therefore achieve significant market penetration, particularly
      at the expense of lansoprazole and the H2 blockers.

PMID- 15989652
TI  - Psoriasis: latest advances in understanding and novel therapeutic approaches.
AB  - Psoriasis is a chronic disabling skin disorder which is the end result of a
      pathological process involving genetic and environmental elements. Both a T-cell
      origin and a primary defect in keratinocytes have been considered as the starting
      point. Recently, transgenic animal models and severe combined immunodeficiency
      (SCID) grafting have been developed. Research into the basic biology and
      immunology of psoriasis is generating a wide range of new treatments, including
      differentiating agents and immunomodulatory drugs. Flaws in conducting clinical
      trials of psoriasis have been repeatedly described, and methodological
      improvements are required.

PMID- 15989654
TI  - Drugs for cardiovascular disease. Spoilt for choice?
AB  - It is believed that the number of drugs, and indeed different classes of drugs,
      potentially available for treating cardiovascular disease has increased
      enormously. The object of this conference, held at the Royal College of
      Physicians in London on 1st and 2nd May 1997, was to evaluate both current
      treatment options and alternative research strategies.

PMID- 15989653
TI  - The 97th Annual Meeting of the American Society for Microbiology.
AB  - The Annual Meeting of the American Society for Microbiology took place in Miami
      Beach, Florida, from May 4-8, 1997. Over 9000 scientists attended this meeting,
      which covers all major aspects of prokaryotic research (basic, applied, medical,
      and diagnostic). Genomics discussions were a major part of the meeting agenda,
      with scientists detailing both basic and applied research effort using genomics
      and bioinformatics. New ideas for potential novel antimicrobials have also
      surfaced as the tools to pursue Drug Discovery have fallen into place and
      pharmaceutical companies have ;rediscovered' anti-infectives.

PMID- 15989655
TI  - Viral resistance patterns selected by antiretroviral drugs and their potential to
      guide treatment choice.
AB  - Massive viral turnover and reverse transcriptase's high error rate create the
      potential for drug-resistant viral variants to appear rapidly under the selective
      pressure of antiretroviral therapy. Loss of antiviral effect in treatment
      adherent persons is most commonly coincident with the appearance of viral mutants
      with reduced drug sensitivity. Thus, detection of viral resistance may represent
      an early marker of therapy failure. Similarly, control of viral replication in
      the plasma compartment, as defined by plasma viral load below the levels of assay
      quantification, is associated with a sustained therapeutic response and delayed
      development of viral resistance. Information on patterns of resistance to and
      cross-resistance between antiretroviral agents is increasingly well characterised
      and represents an important consideration when deciding how to combine and/or
      sequence antiretrovirals to achieve optimal antiviral effects. Given the limited
      number of antiretrovirals presently available or in advanced development, it is
      important not to limit future therapeutic options by using therapies early in the
      treatment sequence which may select for cross-resistant viral variants and hence
      potentially reduce the magnitude of therapeutic response when treatment is
      changed to another member of that drug class. However, no studies using
      resistance to guide clinical decision making have been reported to date and
      available sequencing studies have focused largely on switching or adding
      therapies to patients experienced with zidovudine monotherapy. Thus, no
      resistance driven treatment algorithm is currently available.

PMID- 15989656
TI  - Assays for HIV with improved sensitivity and specificity.
AB  - Increased knowledge of the human immunodeficiency virus (HIV) and the infection
      it causes in humans has resulted in an enormous expansion in the understanding of
      viral parameters and host changes. HIV is a virus which mutates readily and
      rapidly, presenting many challenges to assay developers, and monitors of therapy
      and drug-resistance. Prolific viral replication at all the stages of the disease
      means that an accurate assessment of viral burden, viral load and changes to
      immune system markers is essential for effective clinical management and
      treatment. In the present review we have summarised current opinion on the
      kinetics of HIV infection and the pathogenesis of the disease it causes, and have
      provided a background to the evolution of HIV assays. Sensitivities and
      specificities of assays used for anti-HIV and HIV detection have improved, and
      new assays have been developed employing novel molecular techniques, which are
      being applied to meet continually evolving demands for more sensitive measurement
      of an increasing number of parameters. The future of HIV testing is also
      considered in the light of new knowledge concerning virus dynamics in vivo, the
      likelihood of the emergence of new subtypes and the changing approach to therapy.
      Assays will be, on the whole, used to quantify virus and to measure the host
      reactions to infection, often in the presence of antivirals. Thus, extreme
      sensitivity and specificity will be required.

PMID- 15989657
TI  - Interleukin-12 and infectious diseases: a potential novel therapy.
AB  - Interleukin-12 (IL-12) is emerging as a central component of both innate and
      acquired immunity. The multiplicity of biological activities associated with this
      cytokine, particularly the stimulation of cell-mediated immunity, suggests that
      it may be crucial in the control of extracellular and intracellular infections.
      In in vitro studies, IL-12 production is initiated rapidly after infection with a
      variety of viral, parasitic, fungal and bacterial agents. This induction
      correlates well with the reported resistance or susceptibility of animals to
      infection with these agents. Other factors may, however, influence responses in
      vivo, including host genetic make-up, microbial load and the induction of
      antagonistic cytokine pathways, notably IL-4 and IL-10. In some situations, IL-12
      may direct immune responses to inappropriate pathways, and worsen disease, so
      that careful consideration of the type of required immune response is needed
      before IL-12 therapy is initiated. IL-12 treatment may also be useful in
      promoting protective immune responses to vaccines, allowing systemic immunisation
      with lower doses, or even normally non-immunogenic preparations, of antigen.
      Finally, IL-12 has been demonstrated to act in concert with standard
      antimicrobial chemotherapy in viral, parasitic, fungal and bacterial infections,
      allowing a reduction in the dose of the agent used and providing hope that such
      combination therapy may more effectively control drug-resistant strains of
      infectious agents.

PMID- 15989658
TI  - New developments in the treatment of viral respiratory tract infections.
AB  - Most respiratory tract infections are viral in origin, yet until recently only a
      few effective therapies had been developed. This reflected the large number of
      causative agents and the generally benign course of most infections. However,
      increasing numbers of serious respiratory infections have been seen in recent
      years, due to the rising prevalence of immunodeficient patients and the emergence
      of previously unrecognised pathogens. Better understanding of viral structure,
      and novel methods of drug design and discovery are leading to the development of
      potentially valuable new treatments, particularly for influenza and respiratory
      syncytial virus infection.

PMID- 15989659
TI  - Novel targets for antibiotics--an update.
AB  - The emergence of widespread antibiotic resistance as an impediment in the
      treatment of bacterial diseases is of growing concern. In some instances,
      clinicians are left with few or no antibiotics for treatment of infections and
      this problem will more than likely grow in magnitude. One approach to get around
      the problem of antibiotic resistance is to develop new drugs with novel targets
      and mechanisms of action. Due to the 'newness' of these novel targets as
      therapeutic targets, the likelihood that resistance will initially be widespread
      is low. Three approaches are discussed in this overview: discovery of new
      essential genes that are expressed exclusively in vivo development of compounds
      that act on global bacterial gene regulators; and interference with virulence
      determinants. By exploiting virulence related attributes or genes expressed
      exclusively in vivo, the risk of resistance is reduced since inhibiting these
      products will probably alter the ecology (habitats) of these organisms rather
      than causing direct cell death. This might also lead to a selective targeting of
      pathogens with the beneficial consequence of ignoring organisms growing in their
      normal habitat, such as in the gastrointestinal tract or skin.

PMID- 15989660
TI  - Approaches to antibacterial drug discovery.
AB  - The discovery of new antibacterial drugs can be based either upon empirical
      screening methods or structure-based design. Empirical methods utilise both
      intact bacteria and isolated biochemical targets for high throughput screening of
      natural product or chemical libraries to detect inhibitor leads. Structure-based
      methods for drug design are based upon understanding the molecular architecture
      of the active site in an appropriate target molecule. Empirical methods have been
      widely applied to screen for antibacterial agents and the introduction of
      combinatorial methods for the synthesis of chemical libraries considerably
      expands the potential of empirical screening methods. In contrast, structure
      based drug design has not yet been widely applied to the development of
      antibacterial drugs, although it has proved to be a successful approach in other
      therapeutic areas. Recent advances in the sequencing of bacterial genomes will
      assist both empirical and structure-based approaches by identifying new,
      essential bacterial genes whose products may become the targets of new agents
      with selective antibacterial activity.

PMID- 15989661
TI  - Mechanisms and clinical effects of thiazolidinediones.
AB  - Studies of pioglitazone, troglitazone, BRL 49653 and other thiazolidinediones in
      preclinical animal models of non-insulin dependent diabetes mellitus (NIDDM) and
      obesity led to the observation that these compounds were effective in reducing
      hyperglycaemia and hyperlipidaemia. In these models, animals treated with
      thiazolidinediones had notable improvements in blood glucose levels, hepatic
      glucose output, peripheral insulin resistance, and serum lipid levels.
      Mechanistic studies indicate that thiazolidinediones act at many intracellular
      sites and can influence several processes to increase cell sensitivity to
      insulin. These include influence on insulin receptor kinase activity, control of
      insulin receptor phosphorylation, change in number of insulin receptors, quantity
      and activity of GLUT-4, modulation of tumour necrosis factor (TNF) activity,
      activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and
      alteration of hepatic glucose metabolism. Available data on pioglitazone and
      troglitazone from clinical studies support the efficacy and safety of this class
      of compounds in reducing hyperglycaemia, hypertriglyceridaemia and insulin
      resistance associated with NIDDM. Currently, only troglitazone is approved for
      use in the United States and only in combination with insulin. This new
      pharmacological class of drugs has great promise for the treatment of NIDDM and
      also as a valuable research tool to further the understanding of the mechanisms
      that underlie NIDDM and insulin resistance syndrome.

PMID- 15989662
TI  - New non-sulfonylurea insulin secretagogues.
AB  - Current treatments for non-insulin dependent diabetes mellitus (NIDDM) remain far
      from ideal. The universal finding of islet dysfunction characterised by the
      absence of first phase insulin secretion, even prior to the level of
      hyperglycaemia diagnostic of NIDDM, challenges the rationale for treatments that
      only enhance insulin action. To date, however, the sulfonylureas are the only
      insulin secretagogues available and even the most rapid acting of these fail to
      restore early insulin release in response to meals. Four novel non-sulfonylurea
      insulin secretagogues are in advanced clinical development: A-4166, KAD-1229, BTS
      67 582 and repaglinide. These promising new agents control prandial
      hyperglycaemia by augmenting the early insulin response to meals. Preclinical and
      early clinical data suggest that their potencies vary considerably, as do their
      pharmacokinetics and, importantly, their pharmacodynamics. The two shortest
      acting compounds, A-4166 and KAD-1229, will be developed to be taken prior to
      each main meal, while the slower, longer duration agents, repaglinide and BTS 67
      582, may be developed to be taken twice daily. With a sufficiently rapid onset
      and short duration of action, the new non-sulfonylurea insulin secretagogues may
      improve or even restore the impairment of early insulin secretion without
      inducing the prolonged hyperinsulinaemia characteristic of sulfonylureas.
      Treatment with these new agents will immediately improve prandial glucose control
      and with continued treatment these agents are expected to improve the overall
      metabolic state. Furthermore, a short-acting secretagogue will have minimal
      propensity to elicit prolonged or delayed hypoglycaemia and it is expected that
      by minimising chronic hyperinsulinaemia the weight gain that accompanies
      sulfonylurea treatment will be avoided. In summary, the new non-sulfonylurea
      insulin secretagogues will make an important contribution to the limited and
      inadequate armamentarium currently available for the treatment of NIDDM, and
      their use in combination with insulin sensitising agents may provide, for the
      first time, an approximation to ideal metabolic control in NIDDM.

PMID- 15989663
TI  - Antiretroviral therapies in HIV-1 infection.
AB  - Recent progress in our understanding of the viral dynamics and immunobiology of
      HIV infection, coupled with the introduction of a new generation of
      antiretroviral agents, has led to significant advances in the medical management
      of HIV infection. Eleven antiretroviral drugs are currently licensed in the
      United States, and eight are licensed in Europe. These include the nucleoside
      reverse transcriptase inhibitors (AZT, ddI, ddC, 3TC and d4T); the non-nucleoside
      reverse transcriptase inhibitors (nevirapine and delavirdine) and the protease
      inhibitors (saquinavir, indinavir and ritonavir). This report summarises recent
      developments in the use of antiretroviral therapies and the main treatment
      strategies under evaluation in current trials. These strategies include the
      evaluation of novel antiretroviral agents; combinations to achieve maximal viral
      suppression; optimal sequencing of antiretroviral agents; and subtraction
      therapy. However, many important issues in the use of antiretroviral therapies
      remain unresolved, including the optimal role of new agents, such as protease
      inhibitors (PIs), and the use of triple combination therapy in initial and
      subsequent treatment regimens; when therapy should be changed; which alternative
      agents should then be used; and the most appropriate methods for monitoring the
      efficacy of therapy.

PMID- 15989664
TI  - Brimonidine.
AB  - Brimonidine tartrate is a highly selective alpha2-adrenergic receptor agonist
      indicated for the chronic treatment of glaucoma and ocular hypertension.
      Glaucoma, a serious worldwide public health problem causing blindness in 5.2
      million people, is treated by drugs that lower the intraocular pressure (IOP), a
      primary risk factor in glaucomatous optic neuropathy. Currently, beta-blockers
      are the most common therapy. In two 12-month clinical comparison trials with
      timolol 0.5% (n = 926), twice-daily brimonidine produced IOP lowering comparable
      to twice-daily timolol. In a 3-month trial with betaxolol 0.25% suspension (n =
      206), twice-daily brimonidine was more effective in lowering IOP than twice-daily
      betaxolol. Brimonidine was well-tolerated ocularly and systemically in these
      trials. It caused no clinically significant mean changes in heart rate or blood
      pressure. Brimonidine produced no significant effect on FEV1 in clinical trials,
      and it is not contraindicated in patients with cardiopulmonary disease.
      Brimonidine 0.2% dosed twice daily has clinical utility as a first-line drug
      therapy. It is an effective and safe alternative to beta-blockers, particularly
      in patients at risk for pulmonary or cardiovascular disease. It decreases aqueous
      humour production and increases uveoscleral outflow, and has an additive ocular
      hypotensive effect used concomitantly with other agents. Brimonidine has
      demonstrated neuroprotective properties in laboratory animal studies. Additional
      studies are warranted to determine whether brimonidine has clinical benefit in
      protecting the optic nerve head from glaucomatous damage. Brimonidine is an
      important contribution to glaucoma management.

PMID- 15989665
TI  - Topiramate: current status and therapeutic potential.
AB  - Topiramate (TPM) is a structurally unique, highly effective new antiepileptic
      drug (AED). Three mechanisms of action that may contribute to TPM anticonvulsant
      activity include modulation of voltage-dependent sodium channels, potentiation of
      gamma-aminobutyric acid (GABA)-induced chloride fluxes and blockade of kainate
      glutamate receptors. TPM is rapidly absorbed, has linear pharmacokinetics, a half
      life of 20 - 30 h in the absence of hepatic-enzyme-inducing AEDs, and few
      pharmacokinetic interactions with other drugs. TPM is not extensively metabolised
      and is excreted renally. The most common adverse effects reported in controlled
      trials were mild to moderate in severity, mainly CNS-related, and occurred most
      frequently during the titration period when the TPM dosage was rapidly increased.
      Combined data from five double-blind, placebo-controlled trials showed TPM
      produced statistically significant reductions in seizures regardless of age,
      gender or baseline seizure frequency. Seizure control appears to be maintained
      with long-term TPM therapy; no evidence of tolerance was seen in patients
      receiving TPM for periods of up to 7 years. Preliminary findings on TPM as
      monotherapy for partial epilepsy and as adjunctive therapy for generalised tonic
      clonic seizures of non-focal origin, Lennox-Gastaut syndrome, and partial
      epilepsy in children have been promising.

PMID- 15989666
TI  - Alteplase.
AB  - Alteplase (recombinant human tissue type plasminogen activator, rt-PA) was
      identified as a naturally occurring plasminogen activator in 1975, cloned from a
      human melanoma cell line in 1981, introduced into clinical trials in 1982, and
      received a product licence for the treatment of acute myocardial infarction in
      1986. The present review will concentrate on assessing its current status as a
      clinically effective thrombolytic agent, but will touch briefly on its
      biochemical, physiological and pharmacological properties. Since alteplase is an
      approved pharmaceutical name, the term tPA will be used to refer to the naturally
      occurring substance in its physiological context.

PMID- 15989667
TI  - Reteplase (r-PA): a new plasminogen activator.
AB  - Reteplase (r-PA) is a genetically engineered deletion mutant of wild-type tissue
      type plasminogen activator. The structural differences lead to different
      functional properties, such as a prolonged half-life. The compound demonstrated
      good thrombolytic efficacy in in vitro as well as in animal studies. In
      angiographically controlled patency studies (GRECO, GRECO-2 RAPID-1, RAPID-2),
      the double-bolus application scheme was established, and a superior patency
      profile for reteplase in comparison to alteplase was demonstrated. Mortality
      studies established reteplase as a safe drug with a 30-day mortality at least
      equivalent to streptokinase (INJECT) and very similar to alteplase (GUSTO-3). A
      possible advantage may be the double-bolus application without a need for weight
      adjustment, especially in a prehospital setting. Thus, reteplase can be regarded
      as an excellent alternative to streptokinase or alteplase for thrombolytic
      therapy in acute myocardial infarction.

PMID- 15989668
TI  - TNF-alpha antagonists: monoclonal antibodies, soluble receptors, thalidomide and
      other novel approaches.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic molecule produced in
      response to a variety of stimuli during normal host defence. At low levels, TNF
      alpha confers protection against infectious agents, tumours and tissue damage,
      and plays a role in the development of humoral immunity. However, overproduction
      of TNF-alpha has been implicated in the pathogenesis of a wide variety of
      conditions, including autoimmunity, malignancy, inflammatory and
      immunopathological diseases. Furthermore, TNF-alpha is a key regulator of other
      pro-inflammatory cytokines; infiltrating mononuclear cells that produce excessive
      amounts of TNF-alpha at sites of inflammation are, therefore, primary targets for
      therapeutic intervention. Traditional anti-inflammatory drugs, such as
      cyclosporin, have widespread immunosuppressive effects and are now being replaced
      by more specific anti-TNF-alpha compounds. In this report, work presented at the
      recent Cambridge Symposia meeting on TNF-alpha antagonists in Santa Fe, New
      Mexico, will be highlighted and discussed.

PMID- 15989669
TI  - Eighth European meeting on hypertension.
AB  - The Eighth European Meeting on Hypertension, held in Milan, Italy, was attended
      by approximately 4000 people. The programme consisted of 120 presentations, 337
      poster sessions, 6 invited lectures/debates (endothelin antagonists; cardiac
      renin-angiotensin system; cancer and hypertension; adducin; angiotensin
      converting enzyme (ACE) gene polymorphism; pulse pressure) and 2 plenary sessions
      on 'sleep apnea and hypertension' and 'treatment of hypertension in the elderly'.

PMID- 15989670
TI  - 57th American Diabetes Association annual meeting.
AB  - The annual meeting of the American Diabetes Association was held in Boston, MA.
      There were over 6500 participants, one-third from overseas, and 1103 papers were
      presented. Abstracts from the meeting have been published, from which abstract
      numbers are given below, e.g., (A141). Considerable progress has been made in
      understanding the complexities of diabetes and obesity, and new treatments for
      diabetes and associated metabolic diseases have great potential. These are likely
      to expand greatly by the further elucidation of specific metabolic defects that
      exist, improved diagnosis of the existing disease, as well as the development of
      novel or as yet under-utilised drugs.

PMID- 15989671
TI  - Recurrent glomerulonephritis in the renal allograft: an update of selected areas.
AB  - Glomerular diseases, including diabetes and various forms of glomerulonephritis,
      account for more than 70% of patients undergoing renal transplantation. Among
      these patients, more than 40% develop significant proteinuria, and around 15%
      develop persistent nephrotic syndrome. The most common cause of
      posttransplantation proteinuria is chronic allograft nephropathy (60%), followed
      by recurrent (15%) and de novo (10%) glomerulonephritis. Persistent proteinuria
      is associated with a significantly reduced rate of graft survival but often can
      be controlled with non-disease-specific therapy including angiotensin-converting
      enzyme inhibitors and angiotensin receptor blockers with favorable effects on
      long-term prognosis. Recurrent or de novo glomerulonephritis occurs in 6%-20% of
      patients overall and is more common in patients transplanted with
      glomerulonephritic organs. Glomerulonephritis in the allograft is also associated
      with a reduction in long-term (5-year) graft survival (40% vs 70%). The most
      common diseases associated with allograft glomerulonephritis and their recurrence
      rates in transplantation patients are idiopathic focal glomerular sclerosis (20%
      30%), IgA nephropathy (25%), membranoproliferative glomerulonephritis (type 1,
      25%; type 2, 80%), membranous nephropathy (30%), and hemolytic-uremic syndrome
      (classic, 10%; atypical, 40%; familial, 60%). This article reviews new
      developments in the understanding of 3 of these diseases-focal glomerular
      sclerosis, membranous nephropathy, and hemolytic-uremic syndrome-as they relate
      to the incidence of recurrence, the effects of recurrence on graft survival, risk
      factors for recurrence, and management issues for nephrologists caring for
      patients with renal allografts. Proper donor selection, early diagnosis in high
      risk patients, and appropriate management can prolong graft survival and improve
      long-term outcomes.

PMID- 15989672
TI  - Bacteremia using the molecular adsorbent recirculating system in patients bridged
      to liver transplantation.
AB  - OBJECTIVE: To retrospectively analyze the incidence and implications of
      bacteremia in patients supported by a molecular adsorbent recirculating system
      bridged to liver transplantation. MATERIAL AND METHODS: From September 2000 to
      April 2003, 30 patients (17 males and 13 females, aged 15-70 years; median age,
      52 years) presenting with acute-on-chronic liver failure were treated with a
      molecular adsorbent recirculating system. RESULTS: Nine patients (30%) developed
      bacteremia (positive blood culture) during treatment, 100% of them died during
      the same hospital admission. The most common isolates were Pseudomonas aeruginosa
      (44.4%) and Escherichia coli (33.3%). Sputum (44.4%) and ascites (33.3%)
      represented the most common sources of infection followed by urine and purely
      bloodborne infections (11.1% each). The isolate in the sputum was Pseudomonas
      aeruginosa 100% of the time, whereas Escherichia coli was found in 66.6% of the
      ascites cultures. The hemodynamic profile of patients who developed positive
      blood cultures showed significantly lower systemic vascular resistance indexes
      compared with those of nonbacteremic patients before and after treatment. There
      was a statistically significant difference (P = 0.0002) in survival between the
      bacteremic (who all died) and the nonbacteriemic patients treated. CONCLUSIONS:
      Bacteremia was found to be a negative prognostic factor for patients supported
      with a molecular adsorbent recirculating system and therefore, a contraindication
      to starting and/or continuing treatment. Infection should be carefully ruled out
      prior to initiating treatment using a molecular adsorbent recirculating system.
      Moreover, prophylaxis with broad-spectrum antibiotics that provide double
      coverage against Gram-negative bacteria should be mandatory.

PMID- 15989673
TI  - Cyclosporine lymphocyte maximum level: a new alternative for cyclosporine
      monitoring in kidney transplantation.
AB  - OBJECTIVES: To determine the relationship between clinical outcome, lymphocyte
      count (LC), and cyclosporine (CsA) lymphocyte maximum level (LT(m)L) in kidney
      transplant recipients. MATERIALS AND METHODS: CsA LT(m)L was determined in
      patients with biopsy-proven graft dysfunction and in patients with normal graft
      function. Clinical outcome was compared according to CsA LT(m)L, dosage, blood
      trough (C(0)) and maximum (C(max)) levels, hematocrit level, and LC. RESULTS:
      Rejecting patients had significantly lower LT(m)L than did those with normal
      graft function (27 -/+ 11 pg/Lc vs 71 -/+ 79 pg/Lc; P < 0.01) and similar LTmL to
      those with nephrotoxicity (27 -/+ 8 pg/Lc). Patients with normal graft function
      exhibited significantly lower LC (0.001292 -/+ 696 x 10(9)/L) and serum
      creatinine levels (88.4 -/+ 35 micromol/L) when compared with rejecting patients
      (0.001717 -/+ 364 x 10(9)/L, 132.6 -/+ 8.8 micromol/L) and those with
      nephrotoxicity (0.001884 -/+ 582 x 10(9)/L, 123.7 -/+ 8.8 micromol/L) (P < 0.03,
      P < 0.001). No significant difference was observed among the 3 groups with regard
      to CsA dosage, C(0), C(max), mycophenolate mofetil (MMF) dosage, and mycophenolic
      acid (MPA) plasma levels. CsA LT(m)L closely correlated in an exponential (R(2) =
      0.98) and linear (R(2) = 0.35) fashion with LC and hematocrit level,
      respectively. Conversely, CsA C(max) failed to correlate with C(0) and these 2
      latter parameters. Weak correlations were observed between CsA C(max) and its
      corresponding LT(m)L. CONCLUSIONS: CsA LT(m)L appears to correlate better than
      CsA C(max) with rejection-free outcome and LC. An increase in hematocrit appears
      to have an adverse effect on CsA lymphocyte binding. CsA LT(m)L may offer a new
      alternative for CsA monitoring in kidney transplantation.

PMID- 15989674
TI  - Organ donations from deceased persons in the Saudi Arabian population.
AB  - OBJECTIVE: We aimed to determine the factors that influence organ donation
      consent and refusal in Saudi Arabia and see if they are different from those
      reported elsewhere. By determining these, we hope to introduce strategies to
      enhance donor consent by families of deceased persons. METHODS: We examined next
      of-kin records of Saudi brain dead persons who had been approached for consent
      for donation during 1998. These same next of kin were approached in 2004 and
      asked to fill out a questionnaire examining demographics, awareness, and emotions
      regarding their decision to donate a family member's organ(s). In addition, data
      related to the deceased persons also were recorded. RESULTS: During 1998, 41
      Saudi next of kin had been approached for permission to obtain organs from their
      deceased relatives. Of these, 16 consented and 25 did not. We obtained responses
      from all the consenters (group 1) and from 16 of the nonconsenters (group 2). The
      consenters were more educated; had positive feelings about donation and still do;
      and had keener knowledge regarding organ donation, religious standpoints about
      donation, and the results of transplantation. CONCLUSIONS: The results
      demonstrate that consent for donation depends on prior knowledge and awareness of
      the various aspects of organ donation. Public education methods used to encourage
      organ donation need review. We found no differences in economic status or age
      between consenters and nonconsenters. The relationship between the deceased
      person and the next of kin does not appear to play a role in determining consent
      or refusal. On the other hand, consent was less likely when death was caused by a
      motor vehicle accident than it when other factors led to death.

PMID- 15989675
TI  - Hepatocyte transplantation: a review of worldwide clinical developments and
      experiences.
AB  - Hepatocyte transplantation is a promising treatment for several liver diseases
      and can also be used as a "bridge" to liver transplantation in cases of liver
      failure. Although the first animal experiments with this technique began in 1967,
      it was first applied in humans in 1992. Clearly, the most important advantage of
      this treatment, compared with liver transplantation, is its simplicity, since no
      surgery is required for implantation of the cells. Much work has been done over
      the years to maximize the number of viable hepatocytes that can be isolated from
      a liver, to prepare the cells prior to transplantation so that the outcome will
      be more successful, and to identify the optimal site for implantation. We review
      these efforts along with the worldwide clinical experience with hepatocyte
      transplantation during the last 13 years.

PMID- 15989676
TI  - Improvement in isolation of human peripheral blood leukocyte subpopulations:
      application in diagnosing human cytomegalovirus infection in bone marrow
      transplant patients.
AB  - OBJECTIVES: High-yield isolation and purification of human leukocyte
      subpopulations from whole blood is fundamental to many biological and medical
      applications including qualitative and quantitative PCR-based techniques of
      determining human cytomegalovirus infection. Several procedures have been
      reported to purify morphologically and functionally intact human leukocyte
      subpopulations for diagnostic proposes. Here, we report and evaluate a technique
      for high-yield purification of intact and viable human leukocyte subpopulations
      based on modification of a previous methodology. MATERIALS AND METHODS: One
      hundred peripheral blood samples were collected from bone marrow transplant
      recipients (n = 60), bone marrow donors (n = 20), and healthy blood donors (n =
      20). The samples were tested in parallel using 4 different leukocyte separation
      methods. The methods were evaluated based on the concentration, purity, and
      viability of the isolated leukocyte subpopulations. RESULTS: When compared with
      standard methods, our methods produced 99% purity for both polymorphonuclear or
      mononuclear leukocytes. The corresponding viability for the methods was
      determined to be 98%. No erythrocyte contamination was demonstrated. However, the
      maximum concentration for polymorphonuclear or mononuclear leukocytes obtained by
      standard methods was 70%. The corresponding viability for all the methods was
      determined to be 98%. CONCLUSIONS: Our results indicate that in patients with
      decreased whole blood leukocyte numbers, using either a modified Ficoll NH(4)Cl
      or a modified dextran method would be valuable for simultaneous separation of
      polymorphonuclear and mononuclear leukocytes with high purity, viability, and
      concentration.

PMID- 15989677
TI  - Induction therapy.
AB  - Transplantation is a suitable option for patients with end-stage organ failure.
      Many immunosuppressive agents are available, and this may pose difficulty in
      choosing an appropriate combination for maintenance therapy, treating episodes of
      acute rejection of varying severities, and tailoring therapies for specific
      patients. Induction therapy strategies are accomplished either by relatively high
      doses of conventional immunosuppressants or by using poly- or monoclonal
      antibodies. These antibodies are an integral part of transplant medicine today.
      The rationale for antibody therapy aims at augmenting immunosuppression, ensuring
      that delayed introduction of calcineurin inhibitors is safe, encouraging steroid
      withdrawal, and facilitating treatment of patients sensitized to human leukocytic
      antigens in addition to its crucial role in immunologic conditioning either by
      tolerance induction or alternatively minimizing the immunosuppressive drugs.
      Different trends in induction therapy initially consisted of anti-thymocyte
      globulin, then anti- CD3 Orthoclone, and finally anti-CD20, 25, and 52 agents.
      Induction therapy is associated with beneficial short- and long-term outcomes
      when increased risk of adverse effects related to immune system suppression are
      an issue, especially from cytomegalovirus and lymphomas.

PMID- 15989678
TI  - Weight-gain-related factors in renal transplantation.
AB  - OBJECTIVES: Previous studies of renal transplant recipients have suggested that
      weight gain after transplantation is relatively common. The purpose of this study
      was to define the occurrence, magnitude, and predictors of weight gain in this
      group. MATERIAL AND METHODS: We conducted a prospective study of 100 renal
      transplant recipients from 2002 to 2004 at Imam-Reza Hospital in Mashhad, Iran,
      to identify patterns of weight change attributed to sex, age at transplantation,
      socioeconomic class, and duration of dialysis. A descriptive study also was made
      on serum cholesterol and triglyceride levels in renal transplant recipients 12
      months after transplantation. Patients' weights were evaluated at 3, 6, 9, and 12
      months after transplantation. RESULTS: Univariate analyses at 1 year
      posttransplantation showed that women had greater weight gains than did men (P =
      0.003); older recipients had greater weight gains than did younger recipients (P
      = 0.009); weight gain was correlated with an increase in serum triglyceride and
      cholesterol levels (P = 0.000 and P = 0.004); and socioeconomic class was not
      correlated with weight changes (P = 0.955). CONCLUSIONS: Female sex, older age,
      and increasing incidences of hypercholesterolemia and hypertriglyceridemia were
      significantly associated with weight gain 1 year after organ transplantation.

PMID- 15989679
TI  - Transplantation activities in Iran.
AB  - Iran is a tropical country with a land area of 1,648,000 square kilometers and a
      population of 68,100,000. Iran has a recorded history that dates back 2553 years.
      Its earliest medical school was Pasargad. Jondi Chapour University was founded
      1753 years ago during the Sassanid dynasty as a center for higher education in
      medicine, philosophy, and pharmacology. Indeed, the idea of xenotransplantation
      dates back to days of Achaemenidae (Achaemenian dynasty), as evidenced by
      engravings of many mythologic chimeras still present in Persepolis. Avicenna (980
      1037 AD), the great Iranian physician, performed the first nerve repair.
      Transplantation progress in Iran follows roughly the same pattern as that of the
      rest of the world, with some 10-20 years' delay. Modern organ transplantation
      dates back to 1935, when the first cornea transplant was performed at Farabi
      Hospital in Tehran, Iran. The first living-related kidney transplantation
      performed at Shiraz University Hospital dates back to 1968. The first bone marrow
      transplant was performed at Dr. Shariaati's Hospital in Tehran. The first heart
      transplant was performed 1993 in Tabriz, Iran. The first liver transplant was
      performed in 1993 in Shiraz. The first lung transplant was performed in 2001, and
      the first heart and lung transplants were performed in 2002, both at Tehran. In
      late 1985, the renal transplantation program was officially started in a major
      university hospital in Tehran and was poised to carry out 2 to 4 transplantations
      each week. Soon, another large center initiated a similar program. Both of these
      centers accepted surgical, medical, and nursing teams from other academic medical
      centers for training in kidney transplantation. Since 2002, Iran has grown to
      include 23 active renal, 68 cornea, 2 liver, 4 heart, 2 lung, and 2 bone marrow
      transplantation centers in different cities. In June 2000, the Organ
      Transplantation Brain Death Act was approved by the Parliament, followed by the
      establishment of the Iranian Network for Transplantation Organ Procurement. This
      act helped to expand heart, lung, and liver transplantation programs. By 2003,
      Iran had performed 131 liver, 77 heart, 7 lung, 211 bone marrow, 20,581 cornea,
      and 16,859 liver tranplantations. Sources of these donations were living
      unrelated donor, 82%; cadaver, 10%; and living-related donor, 8%. The 3-year
      renal transplant patient survival rate was 92.9%, and the 40-month graft survival
      rate was 85.9%. Another large step in expanding the transplantation program is
      the construction of the Avi- Cenna (Abou Ali Sina) Transplant Hospital in Shiraz.
      This hospital hopefully will begin operation in 2 years. It will offer the
      opportunity for the exchange and sharing of organs and increased cooperation
      between transplant teams in the Middle East. The hospital offers great promise
      for transplant medicine in Iran and other Persian Gulf countries.

PMID- 15989680
TI  - Can renal scan findings predict biopsy-proven allograft rejection?
AB  - OBJECTIVES: To assess the usefulness of isotopic renogram in diagnosing acute
      renal graft rejection. MATERIALS AND METHODS: Degree of perfusion and allograft
      uptake of tracer were correlated with the clinical and biopsy diagnoses in 15
      postrenal transplant patients with varying degrees of renal impairment.
      Renographic findings and perfusion calculations were done by a blinded observer.
      RESULTS: A strong correlation was found between renal histology and renal scan
      findings in 13 of 15 patients. Sensitivity and specificity of renal scanning in
      diagnosing acute rejection were 85% and 50% respectively (using renal biopsy
      findings as the gold standard). CONCLUSION: Our results demonstrate a strong
      correlation between blinded perfusion assessment and biopsy-proven acute
      rejection. We conclude, therefore, that single renal flow scan with DTPA
      (noninvasive/nonnephrotoxic) allows a physician to tailor therapy for acute renal
      graft dysfunction. We suggest that in cases with a renographic diagnosis of AR,
      the patient should receive standard antirejection therapy. Renal biopsy should be
      reserved for those instances when the renographic findings are not definitive and
      those when the patient fails to respond to a standard methylprednisolone therapy.

PMID- 15989681
TI  - Posttransplant lymphoproliferative disease presenting as adrenal insufficiency:
      case report.
AB  - This is the first reported case of lymphoproliferative disease presenting with
      adrenal insufficiency after liver transplantation. A 38-year-old white man was
      admitted 8 months after transplantation for cryptogenic cirrhosis with fever (38
      39 degrees C), chills, cough, and dyspnea. His blood pressure was 100/70 mm Hg,
      there was pallor of the conjunctiva, and a lymph node was palpable in the left
      groin. Laboratory analyses revealed the following values: serum sodium
      concentration (112 mmol/L), potassium (5.4 mmol/L), hemoglobin (7.8 g/L), white
      blood cell count (7.7 x 10(9)/L), glucose 3.9 (mmol/L), and mildly elevated liver
      functions. Abdominal ultrasound showed multiple hypoechoic solid-appearing
      lesions throughout the liver and spleen. Results of a biopsy specimen of the
      groin node confirmed polymorphic B-cell lymphoma. A negative Epstein- Barr virus
      screen before transplant became positive. The patient's fever increased to 40
      degrees C. He subsequently developed sepsis and later, multiple organ failure.
      Autopsy confirmed extensive abdominal disease. The adrenal glands had been
      completely replaced by the tumor. Primary Epstein-Barr virus infection is
      associated with posttransplant lymphoproliferative disease. Replacement of the
      adrenal glands with a tumor produces a clinical picture of adrenal insufficiency.

PMID- 15989682
TI  - Characterization of the functional role of allosteric site residue Asp102 in the
      regulatory mechanism of human mitochondrial NAD(P)+-dependent malate
      dehydrogenase (malic enzyme).
AB  - Human mitochondrial NAD(P)+-dependent malate dehydrogenase (decarboxylating)
      (malic enzyme) can be specifically and allosterically activated by fumarate. X
      ray crystal structures have revealed conformational changes in the enzyme in the
      absence and in the presence of fumarate. Previous studies have indicated that
      fumarate is bound to the allosteric pocket via Arg67 and Arg91. Mutation of these
      residues almost abolishes the activating effect of fumarate. However, these amino
      acid residues are conserved in some enzymes that are not activated by fumarate,
      suggesting that there may be additional factors controlling the activation
      mechanism. In the present study, we tried to delineate the detailed molecular
      mechanism of activation of the enzyme by fumarate. Site-directed mutagenesis was
      used to replace Asp102, which is one of the charged amino acids in the fumarate
      binding pocket and is not conserved in other decarboxylating malate
      dehydrogenases. In order to explore the charge effect of this residue, Asp102 was
      replaced by alanine, glutamate or lysine. Our experimental data clearly indicate
      the importance of Asp102 for activation by fumarate. Mutation of Asp102 to Ala or
      Lys significantly attenuated the activating effect of fumarate on the enzyme.
      Kinetic parameters indicate that the effect of fumarate was mainly to decrease
      the K(m) values for malate, Mg2+ and NAD+, but it did not notably elevate kcat.
      The apparent substrate K(m) values were reduced by increasing concentrations of
      fumarate. Furthermore, the greatest effect of fumarate activation was apparent at
      low malate, Mg2+ or NAD+ concentrations. The K(act) values were reduced with
      increasing concentrations of malate, Mg2+ and NAD+. The Asp102 mutants, however,
      are much less sensitive to regulation by fumarate. Mutation of Asp102 leads to
      the desensitization of the co-operative effect between fumarate and substrates of
      the enzyme.

PMID- 15989683
TI  - Choosing the optimal endpoint(s) for a clinical trial on transfusion.

PMID- 15989684
TI  - Endpoints in clinical trials involving hemostasis and bleeding in patients with
      hemophilia.

PMID- 15989685
TI  - Endpoints in clinical trials of fluid resuscitation of patients with traumatic
      injuries.

PMID- 15989686
TI  - Endpoints in clinical trials on transfusion requirements: the need for a
      structured approach.

PMID- 15989687
TI  - Regulatory perspectives on clinical trials for trauma, transfusion, and
      hemostasis.

PMID- 15989688
TI  - Benign gastro-bronchial fistula - an uncommon complication of esophagectomy: case
      report.
AB  - BACKGROUND: Gastro-bronchial fistula (GBF) is a rare and devastating complication
      following esophagectomy. Making the correct diagnosis is difficult and there is
      no agreement on the treatment for this rare condition. CASE PRESENTATION: We
      report the case of a 56-year-old man who presented with features of repeated
      aspiration and chest infections six years following an esophagectomy for
      Barrett's esophagus. Despite extensive investigations the cause of symptoms was
      difficult to determine. The correct diagnosis of fistula from stomach to right
      main stem bronchus was made at bronchoscopy under general anesthesia. After
      ruling out local recurrence of cancer, a successful primary repair was carried
      out by resection of fistula and direct repair of gastric conduit and bronchus. He
      is well after 6 months of treatment. CONCLUSION: Late development of gastro
      bronchial fistula is a rare complication of esophageal resection that may be
      difficult to diagnose. Surgical resection and direct closure is the treatment of
      choice, although the method of treatment should be tailored according to the
      anatomy of the fistula and the patient's condition.

PMID- 15989689
TI  - Central inhibition and placebo analgesia.

PMID- 15989690
TI  - The basophil activation test by flow cytometry: recent developments in clinical
      studies, standardization and emerging perspectives.
AB  - The diagnosis of immediate allergy is mainly based upon an evocative clinical
      history, positive skin tests (gold standard) and, if available, detection of
      specific IgE. In some complicated cases, functional in vitro tests are necessary.
      The general concept of those tests is to mimic in vitro the contact between
      allergens and circulating basophils. The first approach to basophil functional
      responses was the histamine release test but this has remained controversial due
      to insufficient sensitivity and specificity. During recent years an increasing
      number of studies have demonstrated that flow cytometry is a reliable tool for
      monitoring basophil activation upon allergen challenge by detecting surface
      expression of degranulation/activation markers (CD63 or CD203c). This article
      reviews the recent improvements to the basophil activation test made possible by
      flow cytometry, focusing on the use of anti-CRTH2/DP2 antibodies for basophil
      recognition. On the basis of a new triple staining protocol, the basophil
      activation test has become a standardized tool for in vitro diagnosis of
      immediate allergy. It is also suitable for pharmacological studies on non
      purified human basophils. Multicenter studies are now required for its clinical
      assessment in large patient populations and to define the cut-off values for
      clinical decision-making.

PMID- 15989691
TI  - Comparative modelling of protein structure and its impact on microbial cell
      factories.
AB  - Comparative modeling is becoming an increasingly helpful technique in microbial
      cell factories as the knowledge of the three-dimensional structure of a protein
      would be an invaluable aid to solve problems on protein production. For this
      reason, an introduction to comparative modeling is presented, with special
      emphasis on the basic concepts, opportunities and challenges of protein structure
      prediction. This review is intended to serve as a guide for the biologist who has
      no special expertise and who is not involved in the determination of protein
      structure. Selected applications of comparative modeling in microbial cell
      factories are outlined, and the role of microbial cell factories in the
      structural genomics initiative is discussed.

PMID- 15989692
TI  - Acute hepatic failure and multi-system organ failure secondary to replacement of
      the liver with metastatic melanoma.
AB  - BACKGROUND: Metastatic malignant melanoma to the liver resulting in fulminant
      hepatic failure is a rare occurrence. CASE PRESENTATION: A 46 year old man
      presented to hospital with massive hepatomegaly, elevated liver enzymes and
      increased lactate three weeks following resection of a malignant melanoma from
      his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours
      subsequent to presentation with respiratory failure requiring mechanical
      ventilation, distributive shock requiring high dose vasopressor infusion,
      coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and
      severe metabolic abnormalities including hyperkalemia, acidosis,
      hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive
      physiologic support he received palliation. Autopsy revealed >80% liver
      infiltration by metastatic malignant melanoma. CONCLUSION: We report a case of
      fulminant hepatic failure secondary to metastatic malignant melanoma infiltration
      of the liver.

PMID- 15989693
TI  - Overexpression of cathepsin F, matrix metalloproteinases 11 and 12 in cervical
      cancer.
AB  - BACKGROUND: Cervical carcinoma (CC) is one of the most common cancers among women
      worldwide and the first cause of death among the Mexican female population. CC
      progression shows a continuum of neoplastic transitions until invasion. Matrix
      metalloproteinases (MMPs) and cathepsins play a central role on the enhancement
      of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and
      connective tissue degradation. MMPs -2 and -9 expression has been widely studied
      in cervical cancer. Nevertheless, no other metalloproteinases or cathepsins have
      been yet related with the progression and/or invasion of this type of cancer.
      METHODS: Three HPV18 CC cell lines, two HPV16 CC cell lines and three HPV16 tumor
      CC tissues were compared with three morphologically normal, HPV negative,
      cervical specimens by cDNA arrays. Overexpression of selected genes was confirmed
      by end point semiquantitative reverse transcription-PCR with densitometry. In
      situ hybridization and protein expression of selected genes was further studied
      by means of two tissue microarrays, one consisting of 10 HSIL and 15 CC and the
      other one of 15 normal cervical and 10 LSIL tissues. RESULTS: TIMP1, Integrins
      alpha 1 and 4, cadherin 2 and 11, Cathepsins F, B L2, MMP 9, 10 11 and 12 were
      upregulated and Cathepsin S, L, H and C, Cadherins 3 and 4, TIMP3, MMP 13,
      Elastase 2 and Integrin beta 8 were found to be downregulated by cDNA arrays.
      Endpoint RT-PCR with densitometry gave consistent results with the cDNA array
      findings for all three genes selected for study (CTSF, MMP11 and MMP12). In situ
      hybridization of all three genes confirmed overexpression in all the HSIL and CC.
      Two of the selected proteins were detected in LSIL, HSIL and CC by
      immunohistochemistry. CONCLUSION: Novel undetected CC promoting genes have been
      identified. Increased transcription of these genes may result in overexpression
      of proteins, such as CTSF, MMP11 and MMP12 which could contribute to the
      pathogenesis of CC.

PMID- 15989694
TI  - Spinocerebellar ataxia type 17: report of a family with reduced penetrance of an
      unstable Gln49 TBP allele, haplotype analysis supporting a founder effect for
      unstable alleles and comparative analysis of SCA17 genotypes.
AB  - BACKGROUND: Spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder
      in man, is caused by an expanded polymorphic polyglutamine-encoding trinucleotide
      repeat in the gene for TATA-box binding protein (TBP), a main transcription
      factor. Observed pathogenic expansions ranged from 43-63 glutamine (Gln) codons
      (Gln43-63). Reduced penetrance is known for Gln43-48 alleles. In the vast
      majority of families with SCA17 an expanded CAG repeat interrupted by a CAA CAG
      CAA element is inherited stably. RESULTS: Here, we report the first pedigree with
      a Gln49 allele that is a) not interrupted, b) unstable upon transmission, and c)
      associated with reduced penetrance or very late age of onset. The 76-year-old
      father of two SCA17 patients carries the Gln49 TBP allele but presents without
      obvious neurological symptoms. His children with Gln53 and Gln52 developed ataxia
      at the age of 41 and 50. Haplotype analysis of this and a second family both with
      uninterrupted expanded and unstable pathological SCA17 alleles revealed a common
      core genotype not present in the interrupted expansion of an unrelated SCA17
      patient. Review of the literature did not present instability in SCA17 families
      with expanded alleles interrupted by the CAA CAG CAA element. CONCLUSION: The
      presence of a Gln49 SCA17 allele in an asymptomatic 76-year-old male reams the
      discussion of reduced penetrance and genotypes producing very late disease onset.
      In SCA17, uninterrupted expanded alleles of TBP are associated with repeat
      instability and a common founder haplotype. This suggests for uninterrupted
      expanded alleles a mutation mechanism and some clinical genetic features distinct
      from those alleles interrupted by a CAA CAG CAA element.

PMID- 15989695
TI  - Neuro-ophthalmic emergencies for the neurologist.
AB  - A variety of acute neurologic disorders present with visual signs and symptoms.
      In this review the authors focus on those disorders in which the clinical outcome
      is dependent on timely and accurate diagnosis. The first section deals with acute
      visual loss, specifically optic neuritis, ischemic optic neuropathy (ION),
      retinal artery occlusion, and homonymous hemianopia. The authors include a
      discussion of those clinical features that are helpful in distinguishing between
      inflammatory and ischemic optic nerve disease and between arteritic and
      nonarteritic ION. The second section concerns disc edema with an emphasis on the
      prevention of visual loss in patients with increased intracranial pressure. The
      third section deals with abnormal ocular motility, and includes orbital
      inflammatory disease, carotid-cavernous fistulas, painful ophthalmoplegia,
      conjugate gaze palsies, and neuromuscular junction disorders. The final section
      concerns pupillary abnormalities, with a particular emphasis on the dilated pupil
      and on carotid artery dissection. Throughout there are specific guidelines for
      the management of these disorders, and areas are highlighted in which there is
      ongoing controversy.

PMID- 15989696
TI  - Postresuscitation encephalopathy. Current views, management, and prognostication.
AB  - BACKGROUND: Cardiac arrest has a high mortality rate. Postresuscitation
      encephalopathy is commonly associated with significant morbidity. REVIEW SUMMARY:
      Among those patients who achieve a return to spontaneous circulation, more than
      half die during the subsequent hospital course. Few survivors recover without
      significant neurologic disability. Clinical examination is often used for
      predicting subsequent neurologic outcome in these patients. The role of ancillary
      investigations and the judicious combination of these parameters with the
      findings on clinical examination to achieve accurate prognostication is discussed
      in this review. Only a few parameters have a strong predictive value in coma
      after cardiac arrest. These include pupillary light reflexes and motor responses
      at 3 days, absent somatosensory evoked potential, and possibly diffuse magnetic
      resonance imaging changes. CONCLUSION: The authors discuss the physiology,
      pathology, and consequences of cardiac arrest to the central nervous system, and
      the use of various parameters in prognostication. Induced hypothermia is a new
      therapeutic development.

PMID- 15989697
TI  - Facial pain.
AB  - Facial pain is a common symptom that may be a feature of a primary headache
      disorder or a secondary feature of organic disease. A thorough clinical history
      and physical examination may reveal the characteristic clinical features and
      assist in diagnosis. However, in some cases, the etiology may remain
      indeterminate.

PMID- 15989698
TI  - 10 most commonly asked questions about idiopathic inflammatory myopathies.

PMID- 15989699
TI  - Cluster headaches.

PMID- 15989700
TI  - 9th Annual International Congress on Hematologic Malignancies, Whistler, BC,
      Canada; 41st Annual Meeting of the American Society of Clinical Oncology,
      Orlando, FL; 46th Annual Meeting of the American Society of Hematology, San
      Diego, CA.

PMID- 15989701
TI  - Adult Burkitt's lymphoma.
AB  - Burkitt's lymphoma is a mature B-cell lymphoma that is characterized by a rapid
      proliferative rate and propensity for extranodal sites of involvement such as the
      gastrointestinal tract and central nervous system. This subtype of non-Hodgkin's
      lymphoma is associated with unique cytogenetic translocations involving the c-MYC
      oncogene on chromosome 8, which appears to be involved in the pathogenesis of
      this disease. Although current literature is limited by a lack of randomized
      trials, Burkitt's lymphoma appears to be curable in a high proportion of cases if
      treated with aggressive multiagent chemotherapy regimens. The use of autologous
      stem cell transplantation appears to benefit patients who have had chemotherapy
      sensitive relapses. The role of allogeneic stem cell transplantation for this
      disease remains uncertain. Patients with HIV-associated Burkitt's lymphoma appear
      to have a better prognosis today, which is likely a result of more effective
      antiretroviral therapy and the ability to treat selected patients with more
      aggressive chemotherapeutic regimens than before. This article will review the
      epidemiologic, biologic, diagnostic, and therapeutic aspects of Burkitt's
      lymphoma in adults.

PMID- 15989702
TI  - Prognosis of follicular lymphomas.
AB  - Although numerous treatment approaches are proposed for patients with follicular
      lymphoma, criteria to help in choosing a treatment for a given patient and for
      comparing trial results are lacking. Several retrospective studies have analyzed
      prognostic factors, but their conclusions rely on limited numbers of patients
      treated during long periods, and their results are discordant. The Follicular
      Lymphoma International Prognostic Index was designed from the data recorded over
      8 years of nearly 5000 patients registered worldwide. Five factors are used (age,
      Ann Arbor stage, number of nodal sites, serum lactate dehydrogenase level, and
      hemoglobin level) to build a 3-category index. This index, together with new
      biologic markers such as gene profiling and proteomics, could help provide an
      optimal treatment option for patients with follicular lymphoma.

PMID- 15989703
TI  - The combination of fludarabine, cyclophosphamide, and granulocyte-macrophage
      colony-stimulating factor in the treatment of patients with relapsed chronic
      lymphocytic leukemia and low-grade Non-Hodgkin's lymphoma.
AB  - PURPOSE: The goal of this study was to evaluate the efficacy of the
      fludarabine/cyclophosphamide combination in patients with relapsed chronic
      lymphocytic lymphoma (CLL) and low-grade non-Hodgkin's lymphoma (NHL) and to
      assess the impact of adding granulocyte-macrophage colony-stimulating factor (GM
      CSF) to this regimen in a randomized fashion. PATIENTS AND METHODS: Thirty-four
      patients (CLL, n=16; low-grade NHL, n=18) were enrolled. The median number of
      previous treatments was 2. Patients received <or=6 cycles of fludarabine at 30
      mg/m2 per day and cyclophosphamide at 300 mg/m2 per day on days 1-3 of a 28-day
      cycle. Patients were randomized to supportive care or to receive GM-CSF at 250
      mg/m2 per day, starting 24 hours after completion of chemotherapy and continuing
      up to 48 hours before the next cycle. Those who had received >6 months of
      previous therapy with an alkylating agent or had preexisting cytopenias received
      a 25% dose reduction. Twenty-two patients (65%) were randomized to receive GM
      CSF. Patients completed a median of 5 cycles of treatment (range, 1-6 cycles).
      Twenty-seven patients (80%) received >or=3 cycles of treatment and were evaluated
      for response. RESULTS: Seven patients (26%) exhibited a complete response; 6 of
      the 7 had low-grade NHL. Fourteen patients (52%) exhibited a partial response,
      and 6 patients (22%) had stable disease. Notably, 6 of the 7 patients who
      exhibited complete response and 9 of 14 patients with partial responses were
      randomized to the GM-CSF arm. The duration of response ranged from 4 months to 26
      months. The toxicities were mainly hematologic. Nineteen patients (70%)
      experienced >or=1 episode of grade 3/4 neutropenia, but only 4 (15%) experienced
      febrile neutropenia; 3 of those patients were assigned to the GM-CSF arm.
      CONCLUSIONS: The combination of fludarabine and cyclophosphamide is a well
      tolerated and effective treatment regimen for patients with relapsed CLL and low
      grade NHL. A higher percentage of complete responses were noted in patients with
      low-grade NHL compared with patients with CLL. Granulocyte-macrophage colony
      stimulating factor did not seem to decrease the incidence of febrile neutropenia.
      However, the higher number of complete and partial responses noted on the GM-CSF
      arm is intriguing and warrants further investigation.

PMID- 15989704
TI  - Long-term follow-up high-dose chemotherapy (drug-only program) followed by
      autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas.
AB  - PURPOSE: To investigate the feasibility of high-dose chemotherapy (HDCT) followed
      by autologous stem cell transplantation (ASCT) for aggressive non-Hodgkin's
      lymphoma (NHL), we conducted HDCT with ASCT using a drug-only protocol without
      total body irradiation. Previously untreated and treated adult patients with
      aggressive lymphoma were enrolled onto this study. For the HDCT protocol, we
      developed the AECC regimen, a drug-only regimen consisting of etoposide,
      carboplatin, cyclophosphamide, and nimustine (ie, ACNU). Mobilized peripheral
      blood stem cells were used mainly as a source for ASCT and were used based on
      collection rates of CD34 cells. PATIENTS AND METHODS: Fifty-six patients were
      enrolled and assessed for this study. The median length of follow-up was 6.5
      years, with a range of 0.2-12.5 years. Retrospective immunophenotypic examination
      indicated that the majority of the patients were diagnosed with B-cell lymphoma.
      RESULTS: Before HDCT, 37 patients still had disease (26 partial responses [PRs]
      and 11 cases of no response), and 19 patients exhibited a complete response (CR)
      before HDCT with ASCT. Among 56 patients, 37 (66%) exhibited a CR, including
      patients continuing their first CR and those experiencing a second or further CR,
      and 11 patients (19.6%) exhibited PR on HDCT with ASCT. Outcomes of patients
      without CR were significantly poorer than those of the patients with CR, and 7
      year overall survival rates of patients with and without CR were 63% and 27.2%,
      respectively. No patients developed a second malignancy, including leukemia or
      myelodysplastic syndrome. CONCLUSIONS: High-dose chemotherapy followed by ASCT is
      one of the available consolidation therapies for aggressive NHL, and additional
      involved-field irradiation could play a role in the management of patients with
      NHL who do not exhibit a CR after treatment with HDCT containing a drug-only
      program.

PMID- 15989705
TI  - Non-Hodgkin's lymphoma of the breast: a report of 19 cases and a review of the
      literature.
AB  - PURPOSE: Non-Hodgkin's lymphoma of the breast represents 0.04%-0.50% of malignant
      lesions of the mammary gland. In this article, we report a single institution's
      experience with this rare disease. MATERIALS AND METHODS: Between 1982 and 1997,
      19 patients with breast lymphoma were diagnosed, treated, and followed at this
      institution. RESULTS: There were 18 female patients and 1 male patient. All but
      one were cases of aggressive B-cell lymphoma. Ann Arbor stages were IE (n=5), IIE
      (n=9), IIIE (n=2), and IV (n=3). International Prognosis Index scores were 0
      (n=2), 1 (n=8), 2 (n=7), and 3 (n=2). According to the Wiseman and Liao
      classification established in 1972, 11 cases were primary lymphomas of the
      breast, and 8 cases were secondary involvement of the breast. Median survival
      time was 21.5 months (range, 5.1-114.7 months). The 5-year overall survival was
      29%. Median event-free survival time was 8.3 months. The clinical, radiologic,
      and histologic patterns of presentation match previously published data, even if
      the response rates and the survival times seem disappointing, probably because of
      the initial treatment by tumorectomy or mastectomy for some patients.
      CONCLUSIONS: Systemic chemotherapy should be the mainstay of treatment. Based on
      our experience and a review of the literature, the use of Wiseman and Liao's
      classification is questionable. In fact, it fails to detect whether some
      lymphomas of the breast present a specific natural history and therefore require
      specific management. New clinical and histologic criteria are to be identified.

PMID- 15989706
TI  - Activity of gallium nitrate in refractory peripheral T-cell lymphoma.
AB  - Peripheral T-cell lymphomas (PTCLs) are post-thymic malignancies characterized by
      an aggressive clinical course and an inferior outcome with standard therapies.
      The authors report significant clinical activity of infusional gallium nitrate in
      a patient with stage IV PTCL disease refractory to chemotherapy.

PMID- 15989707
TI  - Intravascular large B-Cell lymphoma with bone marrow involvement and superior
      sagittal sinus thrombosis: report of a case successfully treated with a
      CHOP/rituximab combination regimen.
AB  - Intravascular large B-cell lymphoma (ILBCL) is a rare subtype of diffuse large B
      cell lymphoma (as currently recognized by the World Health Organization
      classification) and is characterized by proliferation of mature B-cells within
      the lumina of small and medium vessels. We report on a 66-year-old man who
      presented with a fever of undetermined origin, a splenomegaly, and an elevated
      lactate dehydrogenase level. The diagnosis of ILBCL was established by a bone
      marrow biopsy that showed CD20+ tumor cells confined within the lumina of
      sinuses. A karyotypic analysis obtained from the bone marrow aspirate showed a
      hypotetraploid clone. Magnetic resonance imaging of the brain revealed multiple
      high-signal areas in the periventricular white matter above the tentorium. Focal
      dural enhancement (pachymeningitis) close to the medium third of the superior
      sagittal sinus was also observed and was related to a partial superior sagittal
      sinus thrombosis as confirmed by venous magnetic resonance angiography. After 8
      courses of a CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) plus
      rituximab regimen, normalization of the superior sagittal sinus and of the bone
      marrow was obtained. With a follow-up of 15 months, the patient is still
      considered in complete remission. This observation highlights an unusual vascular
      aspect of ILBCL and the efficacy of the current standard treatment for this age
      group (CHOP/rituximab) in this particularly aggressive lymphoma subtype.

PMID- 15989708
TI  - ABVD, the Stanford V regimen, and BEACOPP for Hodgkin's lymphoma: what should an
      oncologist do?

PMID- 15989709
TI  - Revisiting the use of recombinant erythropoietin in myelodysplastic syndromes.

PMID- 15989710
TI  - A randomized phase III study of gemcitabine, dexamethasone, and cisplatin versus
      dexamethasone, cytarabine, and cisplatin as salvage chemotherapy followed by
      posttransplantation rituximab maintenance therapy versus observation for
      treatment of aggressive B-Cell and T-Cell non-Hodgkin's lymphoma.

PMID- 15989711
TI  - Phase III randomized trial of patient-specific vaccination for previously
      untreated patients with follicular lymphoma in first complete remission: protocol
      summary and interim report.

PMID- 15989724
TI  - Can opportunistic case-finding of paraproteins be clinically justified?
AB  - The addition of serum protein electrophoresis by laboratory staff upon finding an
      increased total protein or globulin appears to be practised widely in the UK. The
      criteria for assessing which samples are subject to electrophoresis vary
      considerably. They consist of initial objective laboratory data subsequently
      modified, somewhat subjectively, by other laboratory data and clinical details,
      but have often been chosen pragmatically. The aim of the practice is to identify
      patients with occult B-cell malignancies that warrant treatment. While it has
      been lent legitimacy in many cases by involving clinical haematologists in
      discussions, the views of other stakeholders, including other physicians and
      patients, have often not been considered, thus raising a number of ethical
      questions that need to be addressed. The practice is reviewed against both
      current knowledge of B-cell malignancies and monoclonal gammopathy of
      undetermined significance and criteria for screening, of which this forms a
      particular example. The arguments for and against addition of electrophoresis are
      finely balanced, partly because of the very limited outcome data available. We
      conclude that those currently following this practice should continue to do so,
      there is a need to establish outcome data as widely as possible according to
      standard criteria and there should be involvement of physicians, patients and
      national bodies in discussions about the practice so that the practical and
      ethical issues can be addressed.

PMID- 15989725
TI  - The effect of plant stanol- and sterol-enriched foods on lipid metabolism, serum
      lipids and coronary heart disease.
AB  - Phytosterols are plant sterols, mainly campesterol and sitosterol, and their
      respective stanols (5alpha-saturated derivatives), which chemically resemble
      cholesterol. They are present in a normal diet and are absorbed proportionally to
      cholesterol, but to a much lesser extent, such that less than 0.1% of serum
      sterols are plant sterols. Phytosterols inhibit intestinal cholesterol
      absorption, and fat-soluble plant stanol esters were introduced as a functional
      food for lowering serum cholesterol in the early 1990s; plant sterol esters
      entered the market at the end of the 1990s. Inhibition of the intestinal
      absorption of cholesterol stimulates cholesterol synthesis, a factor which limits
      serum cholesterol lowering to about 10% with phytosterols. Enrichment of the diet
      with plant stanol esters reduces absorption and serum concentrations of both
      cholesterol and plant sterols, whereas enrichment of the diet with plant sterol
      esters, especially in combination with statins, lowers serum cholesterol but
      increases serum plant sterol levels. Recent studies have suggested that high
      serum plant sterol levels may be associated with increased coincidence of
      coronary heart disease. Estimates of coronary heart disease reduction by 20--25%
      with plant sterols/stanols is based mainly on short-term studies. Long-term
      cholesterol lowering, needed for the prevention of coronary heart disease, may be
      successful with plant stanol esters, which lower serum cholesterol in both
      genders over at least a year.

PMID- 15989726
TI  - Discovery and consequences of apolipoprotein-epsilon(3Groningen): a G-insertion
      in codon 95/96 that is predicted to cause a premature stop codon.
AB  - BACKGROUND: We found an unexplained, persistent discrepancy between the outcomes
      of two apolipoprotein-E (apo-E) genotyping methods for a patient with features of
      familial dysbetalipoproteinaemia (FD). Polymerase chain reaction - restriction
      fragment length polymorphism resulted in the apo-epsilon(2)/epsilon(2) genotype,
      whereas minisequencing indicated apo-epsilon(2)/epsilon(3). The discrepancy was
      predicted to derive from a novel mutation. METHODS: Sequencing of patient DNA,
      set-up of a mutation analysis method and establishment of mutation occurrence in
      19 family members of the proband and investigation of its association with serum
      lipid indices. RESULTS: Sequencing demonstrated a G-insertion in codon 95 or 96
      ((95)AAG-(96-)GAG-->(95)AAG-(96)GGA-G) of the apo-epsilon(3) allele. The
      mutation, designated apo-epsilon(3Groningen), was predicted to cause a
      frameshift, a premature stop codon at codon 146 (AAG-->TAA) and the expression of
      a truncated apo-E protein, if any. Four family members with the apo
      epsilon(3Groningen) were identified. Two family members with apo
      epsilon(3)/epsilon(3Groningen) had serum lipid indices within reference ranges
      but low-serum apo-E. Three subjects with apo-epsilon(2)/epsilon(3Groningen),
      proband included, had serum cholesterol, triglycerides and calculated low-density
      lipoprotein-cholesterol levels above the reference ranges. Their electrophoresis
      pattern showed the classical broad-beta band, indicative of FD. CONCLUSION: Apo
      epsilon(3Groningen) heterozygosity is unlikely to precipitate FD, unless provoked
      by compound apo-epsilon(2) heterozygosity or other FD precipitating factors.

PMID- 15989727
TI  - Markers of oxidative damage, antioxidant status and clinical outcome in
      critically ill patients.
AB  - BACKGROUND: Oxidative stress is a consequence of critical illness, and may have
      an impact on survival. We studied markers of oxidative damage and antioxidant
      (AO) protection and compared them with clinical scores and outcome. METHODS:
      Blood sampling and clinical scoring was carried out on 60 consecutively admitted
      intensive therapy unit (ITU) patients within 24 h of admission and then every
      three days of ITU stay. The patients included 30 surgical and 30 medical
      patients, of whom 46 survived their stay in ITU. Clinical scoring was by Acute
      Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ
      dysfunction (MOD) score and sepsis rating. Oxidative damage was assessed by
      measurement of plasma malondialdehyde (MDA) and F2 isoprostanes (F2 IsoPs). AO
      protection was assessed by measurement of plasma total AO status, AO gap,
      ascorbic acid and the enzymes glutathione peroxidase and superoxide dismutase.
      RESULTS: Both clinical markers, APACHE II and MOD, and oxidative damage markers
      MDA and F2 IsoPs were significantly higher in non-survivors (NS) than in
      survivors (S) at the time of admission. Median (interquartile ranges) were
      (APACHE II), 14[12--17] (S), 20.5[16.7--22.2] (NS),P<0.0001; (MOD), 3.0[2.0--5.0]
      (S), 8.0[4.7--9.2] (NS), P<0.0005; (MDA, mumol/L), 0.22[0.19--0.27] (S),
      0.25[0.20--0.34] (NS), P=0.04 and (F2 IsoPs, pg/mL), 9.7[6.0--9.9] (S), 11.0[9.0-
      12.0] (NS), P=0.01. Oxidative damage markers reduced (improved) in the survivors
      but increased in the non-survivors. There was little difference between the
      groups in AO protection markers. There was a significant positive correlation
      between MOD and markers of oxidative damage at the time of admission (r=0.40,
      P=0.003, F2 IsoPs; r=0.28, P=0.035, MDA) and between the oxidative damage markers
      themselves (r=0.32, P=0.017). CONCLUSION: Increased oxidative stress is
      associated with poor outcome in critically ill patients, and may be a prognostic
      indicator. Oxidative damage markers are more useful than AO protection markers in
      predicting outcome.

PMID- 15989728
TI  - Replacement of immunoassay by LC tandem mass spectrometry for the routine
      measurement of drugs of abuse in oral fluid.
AB  - BACKGROUND: There is increasing interest in the use of oral fluid as the matrix
      for the detection of drugs of abuse which requires the use of sensitive
      immunoassays to achieve the low detection limits required. The use of liquid
      chromatography linked to tandem mass spectrometry (LC/MS/MS) is explored as a
      possible replacement for immunoassay in screening for drugs of abuse in oral
      fluid samples. METHODS: Oral fluid samples collected from 72 subjects attending
      an addiction clinic were screened for opiates, cocaine, methadone and
      benzodiazepines using both enzyme-linked immunosorbent assays (ELISA) and
      LC/MS/MS. The latter analysis used a short gradient elution with individual drugs
      detected by multiple reaction monitoring using tandem mass spectrometry. Results
      between the two methods were compared qualitatively using the cut-off
      concentrations defined by the ELISA assays. RESULTS: With regard to the ELISA
      assays which show group specificity, LC/MS/ MS detected the presence of 6
      monoacetylmorphine, morphine or dihydrocodeine in all but two of 49 samples
      positive for opiates. Of 55 samples positive for benzodiazepines by ELISA, all
      but two were confirmed by LC/MS/MS. Overall, LC/MS/MS compared favourably with
      ELISA for detection of specific drugs or their metabolites in the case of
      morphine, methadone and the cocaine metabolite benzoylecgonine. Many of the
      discrepant results between the two assays were a result of samples with drug
      concentrations near to the cut-off concentrations and the imprecision of these
      assays at very low concentrations. CONCLUSION: LC/MS/MS offers a more flexible,
      specific and sensitive alternative to the screening of oral fluid samples for
      drugs of abuse than ELISA. A wide range of drugs and metabolites can be detected
      from a single sample injection.

PMID- 15989729
TI  - The effects of green tea ingestion over four weeks on atherosclerotic markers.
AB  - BACKGROUND: The objective of this study was to evaluate the effects of green tea
      ingestion over four weeks on atherosclerotic biological markers. METHODS: After a
      one-week baseline period, 12 healthy male volunteers aged 28--42 years drank 600
      mL of green tea daily for four weeks. Lipid profile, oxidized low-density
      lipoprotein (ox-LDL), total antioxidant capacity (TAC), C-reactive protein (CRP)
      and soluble cell adhesion molecules were measured at baseline and after two and
      four weeks ingestion of green tea. RESULTS: There was no significant change in
      the concentrations of lipid profile, TAC, CRP, soluble intercellular adhesion
      molecule-1 (sICAM-1), or soluble E-selectin after ingestion of green tea. The
      levels of ox-LDL and soluble vascular cell adhesion molecule-1 (sVCAM-1) were
      significantly decreased after four weeks of green tea ingestion (Wilcoxon signed
      rank test, P=0.006). CONCLUSIONS: The results of this study suggest an in vivo
      anti-oxidative effect for green tea and an influence of green tea on
      atherosclerotic biological markers. The effect of green tea seen on ox-LDL and
      sVCAM-1 provides a potential mechanism for the cardiovascular benefits of regular
      ingestion of green tea.

PMID- 15989731
TI  - Gynaecomastia, hyperprolactinaemia and HIV infection.
AB  - Endocrine complications of human immunodeficiency virus (HIV) and its treatment
      are being increasingly recognized. We discuss the diagnosis and management of an
      HIV seropositive man who presented with bilateral gynaecomastia and
      'hyperprolactinaemia' due to macroprolactin within six months of starting
      antiretroviral therapy. We suggest that the gynaecomastia may be a feature of
      immune reconstitution disease. Measurement of serum prolactin in the
      investigation of gynaecomastia should be reserved for those with
      hypogonadotrophic hypogonadism. Since macroprolactin contributes to circulating
      prolactin in HIV-seropositive subjects, hyperprolactinaemic samples in these
      patients should be tested for macroprolactin.

PMID- 15989730
TI  - A simple precipitation method for measuring sialic acid in apolipoprotein B
      containing lipoproteins in plasma.
AB  - BACKGROUND: A convenient method for the measurement of sialic acid in plasma apoB
      containing lipoproteins is described. METHODS: Dextran sulphate-Mg(2+)
      precipitation and enzymatic sialic acid assay were combined and applied to
      analysis of plasma from 96 healthy controls and 136 hyperlipidaemic subjects of
      types IIa (n=46), IIb (n=43), and IV (n=47). RESULTS: The sialic acid
      concentrations (mean+/-SD) in plasma apoB-containing lipoproteins were 19.4+/
      5.9, 24.3+/-4.7 (P<0.0001 versus normal), 23.0+/-4.7 (P<0.0001), 27.9+/-5.2
      (P<0.0001), and 22.3+/-3.4 mg/L (P<0.002), for normal, all types of
      hyperlipidaemia, types IIa, IIb, and IV, respectively. The contents of sialic
      acid in apoB were 2.03+/-0.41%, 2.09+/-0.35% (no significance versus normal),
      1.86+/-0.27% (P<0.0001), 1.97+/-0.26% (P<0.02), and 2.28+/-0.41% (P<0.002), for
      normal, all types of hyperlipidaemia, types IIa, IIb, and IV, respectively.
      CONCLUSION: The content of sialic acid in apoB decreased significantly in type
      IIa but increased in type IV hyperlipidaemia, which may reflect the presence of
      sialic acid in very low-density lipoprotein apolipoproteins other than apoB. This
      simple precipitation method will be useful to evaluate the sialic acid content in
      low-density lipoprotein in hyperlipidaemic subjects, especially of type IIa.

PMID- 15989732
TI  - Alcohol-associated severe hyperhomocysteinaemia.
AB  - We report the cases of three men with severe hyperhomocysteinaemia that was
      associated with high alcohol intake and which resolved on reduction of alcohol
      intake. Investigation to identify other obvious causes of the
      hyperhomocysteinaemia excluded renal failure and vitamin deficiencies. Alcohol as
      a possible cause of significantly increased plasma homocysteine may be under
      recognized by clinicians.

PMID- 15989733
TI  - Model car fuel poisoning.

PMID- 15989734
TI  - Recurrent dizzy spells: all in the head.

PMID- 15989735
TI  - Estimating GFR from plasma creatinine measurements.

PMID- 15989740
TI  - Normal reference value of hemoglobin of middleaged women and altitude.
AB  - AIM: In order to supply a scientific basis for uniting the normal reference value
      standard of hemoglobin of Chinese middlescent women. METHODS: A research is made
      about the relationship between the normal reference value of 25,917 examples of
      hemoglobin of middlescent women and altitude in 268 areas in China, the normal
      reference values of hemoglobin of middlescent women are determined by the
      hemoglobincyanide method. RESULTS: The correlation between the normal reference
      value of hemoglobin of middlescent women and altitude is quite significant (r =
      0.827). By using the method of univariate linear regression analysis, one
      regression equation is inferred. CONCLUSION: If the altitude values are obtained
      in some areas, the normal reference value of hemoglobin of middlescent women of
      this area can be reckoned by using the regression equation. Furthermore,
      depending on the altitude, China can be divided into three districts: Qingzang
      District, Central District, and Eastern District.

PMID- 15989741
TI  - A real-time PCR assay for the detection and quantitation of Campylobacter jejuni
      using SYBR Green I and the LightCycler.
AB  - Campylobacter jejuni is recognized as a leading human food-borne pathogen.
      Traditional biochemical identification for C. jejuni is not reliable due to
      special growth requirements and the possibility that this bacterium can enter a
      viable but nonculturable (VNC) state. Nucleic acid-based tests have emerged as a
      useful alternative to traditional testing. In this article, we present
      fluorescent quantitative PCR assay for quantitative detection of C. jejuni, the
      assay was carried out using a LightCycler instrument and product formation was
      monitored continuously with the fluorescent double-stranded DNA binding dye SYBR
      Green I. When this assay was applied, the assay positive for all of the isolates
      of C. jejuni tested (11 isolates, including type strain ATCC33560) and negative
      for all other Campylobacter spp. (three isolates) and several other bacteria
      (five species tested). The total assay could be completed in 60 min with a
      detection limit of approximately 1 CFU, and a correlation coefficient was 1.000.
      Result indicated that fluorescent quantitative detection methods provided a
      special, sensitive, rapid, reproducible and accurate method for quantitative
      detection of C. jejuni.

PMID- 15989742
TI  - Helping the poor emerge from "urban barbarism to civic civilization": public
      bathhouses in America, 1890-1915.
AB  - In an era when the luxury of private bathrooms had not yet been made widely
      available to the masses, local charities and municipal governments worked
      feverishly to construct public bathhouses. Reformers, including city officials,
      engineers, physicians, and members of the clergy, increased the number of public
      bath facilities across America from a mere six in 1894 to 49 by 1904. The urban
      poor took tens of millions of showers at the turn of the century as a result.
      What the poor may not have realized, however, is that the reformers of the
      Progressive Era had in mind a form of social engineering. Bathing, they argued,
      not only assisted in the containment of disease; it also served to instill upper
      middle class values of self-respect, morality, and citizenship into the life and
      practice of the poor.

PMID- 15989743
TI  - Lymphoplasmacytic sclerosing pancreato-cholangitis: a case report and review of
      the literature.
AB  - Autoimmune pancreatitis is a rare but important cause of pancreatitis that is
      becoming increasingly recognized in the West. Lymphoplasmacytic sclerosing
      pancreatitis (LPSP) is a benign form of chronic pancreatitis characterized
      clinically by infrequent attacks of abdominal pain, jaundice, and weight loss,
      and pathologically by focal or diffuse chronic or lymphoplasmacytic inflammatory
      infiltrates centered around pancreatic ducts and ductules, accompanied by
      obliterative phlebitis, acinar atrophy, and interstitial fibrosis. It has been
      described alone or as a part of the spectrum of autoimmune gallbladder and
      biliary tract disease, with clinical, radiological, and pathological overlap
      reported with primary sclerosing cholangitis. It has been described as "primary
      sclerosing pancreatitis," "sclerosing cholangitis," "non-alcoholic duct
      destructive chronic pancreatitis," and "autoimmune pancreatitis." We report a
      case of LPSP that mimicked pancreatic adenocarcinoma and was subsequently treated
      with a pylorus-preserving Whipple procedure. This may point towards a primary
      biliary autoimmune process involving the pancreatic duct, causing a benign form
      of chronic pancreatitis that may be difficult to characterize pre-operatively to
      avoid surgery. This case typifies the growing awareness of this relatively
      recently characterized clinical entity, its similar presentation to pancreatic
      carcinoma, and the importance for LPSP to be included in the differential
      diagnosis of pancreaticobiliary disease. Finally, we review the literature.

PMID- 15989744
TI  - Recovery of neuromuscular function after a combination of mivacurium and
      rocuronium.
AB  - PURPOSE: The present study was undertaken to evaluate onset, and early and late
      recovery of neuromuscular block after a combination of mivacurium (M) and
      rocuronium (R). METHODS: In this controlled, randomized study, 45 consenting ASA
      I-II patients were assigned to one of three treatment groups: 2.ED95 R alone
      (2R); 2.ED95 R plus 1.ED95 M (2R1M). or 2.ED95 R plus 2.ED95 M (2R2M).
      Neuromuscular monitoring of the ulnar nerve consisted of surface electrode
      stimulation and force transduction of the adductor pollicis muscle. Stable
      baseline stimulation (1 Hz, square-wave, supramaximal current) was established
      prior to relaxant administration and continued until 95 percent twitch height
      depression (onset). Thereafter, train-of-four stimulation every 10 seconds was
      used to record recovery data until 95 percent recovery (T(95%)). Data were
      analyzed using grouped t-tests, ANOVA, and Newman-Keuls multiple comparison
      tests. Significance was defined at the p < 0.05 level. RESULTS: The addition of
      mivacurium to rocuronium did not accelerate onset of block. The combination
      prolonged the clinical duration (time to 5 percent recovery, T(5%)), but did not
      affect subsequent recovery parameters: T(5%) in the 2R1M and 2R2M groups were 100
      percent and 118 percent longer than in the 2R group, respectively (p < 0.05) the
      T(5-25%) (early recovery) and T(25-75%) (linear recovery) indexes were similar in
      all three groups. CONCLUSIONS: The present study did not note an acceleration of
      block onset when mivacurium was added to rocuronium. The findings suggest that
      the addition of mivacurium (1-2.ED95) to rocuronium (2.ED95) prolongs the
      clinical duration of the longer-acting agent, rocuronium, but has no effect on
      the early or linear recovery indexes of rocuronium. Thus, although clinical
      duration is prolonged, recovery from the combination regimens proceeds as if no
      mivacurium had been added to rocuronium.

PMID- 15989745
TI  - Faculty mentorship and first year students at the Yale School of Medicine:
      reflections and perspective.

PMID- 15989746
TI  - Genome-wide linkage disequilibrium from 100,000 SNPs in the East Finland founder
      population.
AB  - Information about linkage disequilibrium (LD) is important in understanding the
      genome structure and has its applications in association studies. Here we present
      the first genome-wide LD study based on a founder population (East Finland). The
      LD data consist of 118 unrelated individuals and around 480,000 SNP pairs
      genotyped with the Affymetrix 100K genotyping assay. Using the minor allele
      frequency (MAF) limit of .05, the squared correlation coefficient between two
      loci (r(2)) was .48, .37, .28, and .20 for distances of 5, 10, 20, and 40 kb
      respectively. MAF had a significant effect on the mean r(2) so that the extent of
      useful LD (r(2) > .3) varied from 17 kb to 80 kb depending on the limit set for
      the MAF. For D' the effect of MAF was smaller but reflected the possible age of
      the mutation: SNPs with high MAF had lower D' than those with low MAF. The X
      chromosome showed higher D' values than autosomes and the extent of useful LD
      (r(2) > .3) was twice as long on the X chromosome than on the autosomes. Based on
      the results, LD varies across the genome and is correlated to local recombination
      rate between and within chromosomes. However, the recombination rate does not
      explain all the variation found in LD. We also report a number of long
      chromosomal regions where exceptionally high or low LD were detected.

PMID- 15989747
TI  - The first "classical" twin study? Analysis of refractive error using monozygotic
      and dizygotic twins published in 1922.
AB  - The first classical twin studies, recognizing the potential of comparing findings
      in identical twins, have previously been reported to be those by Siemens and by
      Merriman, both published in 1924. However, we would like to bring to attention a
      study performed by Walter Jablonski, 2 years earlier (1922), investigating the
      contribution of heredity to refraction in human eyes. Jablonski examined the eyes
      of 52 twin pairs and by comparing the size of within-pair differences between
      identical and nonidentical twins was able to infer the heritability of a trait.
      Therefore, this is likely to be the first reported classical twin study.

PMID- 15989748
TI  - Quantifying and addressing parameter indeterminacy in the classical twin design.
AB  - The classical twin design (CTD) is the most common method used to infer genetic
      and environmental causes of phenotypic variation. As has long been acknowledged,
      different combinations of the common environment/assortative mating, and
      additive, dominant, and epistatic genetic effects can lead to the same observed
      covariation between twin pairs, meaning that there is an inherent indeterminacy
      in parameter estimates arising from the CTD. The CTD circumvents this
      indeterminacy by assuming that higher-order epistasis is negligible and that the
      effects of either dominant genetic variation or the common environment are
      nonexistent. These assumptions, however, lead to consistent biases in parameter
      estimation. The current paper quantifies these biases and discusses alternative
      strategies for dealing with parameter indeterminacy in twin designs. One strategy
      is to model the similarity among other relatives in addition to twins (extended
      twin-family designs), which reduces but does not eliminate indeterminacy in
      parameter estimates. A more general strategy, applicable to all twin designs, is
      to present the parameter indeterminacy explicitly, as in a graph. Presenting the
      space of mathematically equally likely parameter values is important, not only
      because it aids the proper interpretation of twin design findings, but also
      because it keeps behavioral geneticists themselves mindful of methodological
      assumptions that can easily go unexamined.

PMID- 15989749
TI  - Estimating the extent of parameter bias in the classical twin design: a
      comparison of parameter estimates from extended twin-family and classical twin
      designs.
AB  - The classical twin design (CTD) circumvents parameter indeterminacy by assuming
      (1) negligible higher-order epistasis; and (2) either nonadditive genetic or
      common environmental effects are nonexistent, creating two potential sources of
      bias (Eaves et al., 1978; Grayson, 1989). Because the extended twin-family design
      (ETFD) uses many more unique covariance observations to estimate parameters,
      common environmental and nonadditive genetic parameters can be simultaneously
      estimated. The ETFD thereby corrects for what is likely to be the largest of the
      two sources of bias in CTD parameter estimates (Keller & Coventry, 2005). In the
      current paper, we assess the extent of this and other potential sources of bias
      in the CTD by comparing all published ETFD parameter estimates to CTD parameter
      estimates derived from the same data. CTD estimates of the common environment
      were lower than ETFD estimates of the common environment for some phenotypes, but
      for other phenotypes (e.g., stature in females and certain social attitudes),
      what appeared as the common environment was resolved to be assortative mating in
      the ETFD. On average, CTD estimates of nonadditive genetic factors were 43%
      lower, and additive genetic factors 63% higher, than ETFD estimates. However,
      broad-sense heritability estimates from the CTD were only 18% higher than ETFD
      estimates, highlighting that the CTD is useful for estimating broad-sense but not
      narrow-sense heritability. These results suggest that CTD estimates can be
      misleading when interpreted literally, but useful, albeit coarse, when
      interpreted properly.

PMID- 15989750
TI  - Co-twin dependence modifies heritability of abstinence and alcohol use: a
      population-based study of Finnish twins.
AB  - The role of co-twin dependence (twins' closeness or reliance on the co-twin) was
      examined as a moderator of genetic and environmental influences on alcohol use in
      adolescence and early adulthood in a large longitudinal population-based study of
      Finnish twins (FinnTwin16). The associations between co-twin dependence and
      alcohol use were studied first at an individual level in adolescence (n = 3362)
      and early adulthood (n = 2912). Then, maximum likelihood models were fit to the
      two waves of data from same-sex twin pairs to assess the differences and changes
      in genetic and environmental influences on alcohol use (abstinence, drinking
      frequency, intoxication frequency); N = 1342 pairs in adolescence, and N = 1078
      pairs in early adulthood. Overall, no significant associations were found between
      co-twin dependence and individual alcohol use. However, co-twin dependence
      importantly modulated genetic effects on drinking habits, especially in
      adolescence, but also in early adulthood. Co-twin-dependent twins reported
      greater similarity in their alcohol-related behavior across all alcohol-use
      measures at both time points, and the role of genes and environments varied
      according to co-twin dependence. Shared environmental factors explained most of
      the variation in drinking among co-twin-dependent twins in adolescence and
      contributed to drinking to intoxication during early adulthood. In contrast,
      among co-twin-independent twin pairs, genetic variance contributed significantly
      to all alcohol-use measures at both time-points. An interdependent sibling
      relationship is an important modifier of drinking habits, and it appears to
      reduce the impact of inherited liabilities on alcohol-related behavior especially
      in adolescence.

PMID- 15989751
TI  - Genetic component of noise sensitivity.
AB  - We investigated the genetic component of noise sensitivity using a twin-study
      design. The study sample consisted of 573 same-sexed twin pairs from the Finnish
      Twin Cohort. The 131 monozygotic (MZ) and 442 dizygotic (DZ) twin pairs with an
      age range of 31 to 88 years replied to a questionnaire on noise and health
      related items in 1988. The noise sensitivity of respondents was defined as high,
      quite high, quite low or low. MZ pairs were more similar with regards noise
      sensitivity than DZ pairs, and quantitative genetic modeling indicated
      significant familiality. The best z-fitting genetic model provided an estimate of
      heritability of 36% (95% CI = .20-.50) and when hearing impaired subjects were
      excluded this rose to 40% (95% CI = .24-.54). In conclusion, noise sensitivity
      does aggregate in families and probably has a genetic component.

PMID- 15989752
TI  - Short- and long-term effects of child care on problem behaviors in a Dutch sample
      of twins.
AB  - This study examined the association between early child care on the development
      of behavior problems. At the age of 5 years, child care information was collected
      from parents on a large group of twins who were born between 1985 and 1997.
      Mothers and fathers rated the behavior of the child at ages 3, 7, and 10 years
      using the Child Behavior Checklist (CBCL) and teachers reported on the same
      children's behaviors using the Teacher's Report Form (TRF) at ages 7 and 10. At
      the age of 3 years, children with nonparental child care experiences had more
      externalizing problems than children with only parental child care. The long-term
      effects of quantity of child care were mixed and were only significant for mother
      ratings and for children from families with a low socioeconomic status. Overall,
      the effect sizes of child care were very small (effect sizes were between .12 and
      .23). Children with a larger amount of child care did not show more behavior
      problems, therefore it was questioned whether the increased levels of behavior
      problems could be attributed to quantity of child care.

PMID- 15989753
TI  - A retrospective study of the accuracy of sonographic chorionicity determination
      in twin pregnancies.
AB  - The aim of this study was to determine the accuracy of sonographic chorionicity
      determination in the largest sample of twin pregnancies to date. We
      retrospectively analyzed 463 twin pregnancies delivered over a 6-year period to
      determine in each case what the antenatal sonographic prediction of chorionicity
      was, and then what the subsequent post partum pathological diagnosis of
      chorionicity was. Out of 436 twin pregnancies, 428 were correctly diagnosed for
      chorionicity as confirmed by pathology reports. Sonography as a screening tool
      for monochorionic twin pregnancies has a sensitivity of 100%, a specificity of
      97.9% and a predictive value positive of 88.2%. Transvaginal scanning in the
      first trimester determined twin chorionicity with a sensitivity and a specificity
      of 100%. This study has confirmed in the largest sample to date that sonographic
      chorionicity determination is best done in the first trimester using vaginal
      scans, where it has 100% accuracy.

PMID- 15989754
TI  - The case of monochorionic twin gestation complicated by intrauterine demise of
      one fetus in the first trimester.
AB  - The study investigated the clinical and pathomorphological characteristics of
      monochorionic diamniotic twin gestations complicated by the spontaneous loss of
      one fetus during the first trimester. Nine monochorionic diamniotic twin
      gestations were analyzed in which the demise of one fetus occurred during the
      first trimester. During the course of the study, 178 twin gestations were
      sonographically identified during the first trimester. Forty-three (24.2%) were
      complicated by the intrauterine demise of one fetus before the end of the 12th
      week of pregnancy. Nine cases were monochorionic diamniotic. The gestational age
      of the demised fetuses ranged between 5 and 11 weeks (mean 7.4 weeks). The
      prognoses for the surviving fetuses were rather poor with the surviving co-twin
      dying 1 to 3 weeks after the first twin, with abortion of both fetuses. In only
      one case was gestation concluded on the 40th week with delivery of a live
      neonate. No blood coagulation changes were observed in the affected pregnant
      women, and the one live newborn did not reveal any haematological or neurological
      abnormalities. A postnatal study provided evidence for the history of
      monochorionic diamniotic placentation in all of the cases. In two cases, probable
      causes of fetal death were established (congenital malformation, the presence of
      anastomoses between blood vessels). The obtained results suggest an extremely
      high risk of mortality for the surviving twin fetus following the co-twin's death
      in cases of monochorial placentation. The morphological evaluation of placentas
      and fetal membranes enables the establishment of the type of placenta and, in
      certain cases, the probable cause of the intrauterine demise of one twin fetus
      during the first trimester of monochorionic diamniotic twin gestation.

PMID- 15989755
TI  - Midupper arm circumference (MUAC) changes in late pregnancy predict fetal growth
      in twins.
AB  - The objective of the study was to test the hypothesis that changes in arm
      anthropometry can be used to determine the risk of faltering growth in twin
      gestations. Serial data on midupper arm circumference (MUAC) and maternal weight
      gain were collected from a sample of 156 mothers. Changes in MUAC were monitored
      from 20 to 34 weeks. Women with a large loss of MUAC (greater than 1.5 cm),
      particularly when it occurred within two to four weeks of delivery, were
      significantly heavier, had higher pregravid Body Mass Indexes (BMIs), but gained
      less weight than mothers with no change in MUAC. In analysis of covariance models
      adjusting for length of gestation, black ethnicity, males per twin pair,
      monochorionicity, and baseline MUAC at 20 weeks, a large loss of MUAC was
      associated with significantly lower birthweight (2263 g vs. 2499 g) and
      birthweight z-score (-0.92 SDU vs. -0.39 SDU). Changes in MUAC from 20 to 34
      weeks, and especially near delivery, are significantly associated with fetal
      growth in twin pregnancies. A positive change may indicate that the mother has
      adequate dietary intake or nutrient stores to continue to accrue lean body mass
      and support fetal growth, while a loss of MUAC indicates that dietary intake or
      nutrient stores may be inadequate. This simple, relatively precise, measure of
      change in maternal body composition during pregnancy may be useful in identifying
      twin pregnancies at risk for faltering intrauterine growth, particularly among
      overweight or obese women.

PMID- 15989757
TI  - Development and application of stem cells.

PMID- 15989756
TI  - Memories of the Child Development Center study of adopted monozygotic twins
      reared apart: an unfulfilled promise.

PMID- 15989758
TI  - cDNA microarray in isolation of novel differentially expressed genes related to
      human glioma and clone of a novel full-length gene.
AB  - BACKGROUND: This investigation was undertaken to obtain differentially expressed
      genes related to human glioma using cDNA microarray and the characterization of
      one novel full-length gene. METHODS: Total RNA was extracted from human glioma
      tissues and normal brain tissues, and mRNA was used to make probes. After
      hybridization and washing, the results were scanned using a computer system. The
      gene named 681F05 clone was an expressed gene to human glioma through four-time
      hybridization and scanning. Subsequently northern blot analysis was performed by
      northern blot, 5'RACE and bioinformatics. RESULTS: Fifteen differentially
      expressed genes to human glioma were obtained through four-time hybridization and
      scanning. Northern blot analysis confirmed that 681F05 clone was low-expressed in
      human brain tissues and over-expressed in human glioma tissues. The analysis of
      BLASTn and BLASTx showed that 681F05 clone is two cDNA clones encoding two novel
      proteins that are highly identified to the cyclophilin isoform 10 of C. Elgans,
      respectively. Sequence analysis revealed the two cDNA clones are two different
      splicing variants of a novel cycophilin-like gene (PPIL3a and PPIL3b).
      CONCLUSIONS: cDNA microarray technology can be successfully used to identify
      differentially expressed genes. The novel full-length gene of human PPIL3 may be
      correlated with the formation of human glioma.

PMID- 15989759
TI  - Microsurgical resection of craniopharyngioma of the third ventricle via an
      improved transventricular approach.
AB  - BACKGROUND: Craniopharyngioma of the third ventricle is difficult to treat and
      its therapeutic regimens and operative approaches have been controversial. This
      study was undertaken to probe indications for microsurgical resection of
      craniopharyngioma of the third ventricle via an improved transventricular
      approach, its surgical procedures and therapeutic effects, and prevention of
      postoperative complications. METHODS: Fifty-one patients with craniopharyngioma
      of the third ventricle were treated from January 2000 to October 2004 by an
      improved transventricular approach for removing the tumor via the
      interventricular foramen, the intermedius of the septum pellucidum or choroid
      fissure. Symptoms and signs of the patients, and results of imaging, operation,
      and follow-up were analyzed. RESULTS: Of the 51 patients who had received the
      improved transventricular resection, 4 underwent a combined approach with an
      entrance of the pterion. Forty patients (78.43%) underwent total resection and
      others subtotal resection, without an operative death. Epileptic seizures were
      found in 3 patients (5.88%) and subdural effusion in the operative field in 4
      (7.84%). All patients showed good general conditions after operation, and follow
      up for an average of 27.52 months showed relapse of the tumour in 8 patients
      (15.69%). CONCLUSIONS: Microsurgical resection of craniopharyngioma of the third
      ventricle by an improved transventricular approach has advantages of operative
      safety and efficacy, lower mortality and disability, and less complications.

PMID- 15989760
TI  - Clinical and pathological characteristics of septum pellucidum tumor and choice
      of surgical approaches for its resection.
AB  - BACKGROUND: Tumor involving the septum pellucidum is uncommon. Surgery as the
      main therapeutic procedure for this lesion is a challenge to neurosurgeons. We
      analyzed the clinical characteristics and pathological features of septum
      pellucidum tumor in 41 patients and compared the curative effects of frontal
      transcortical, trans-sulcal and interhemispheric transcallosal approaches.
      METHODS: Clinical characteristics and the pathological features of septum
      pellucidum tumor were investigated retrospectively in 41 patients. The
      differences in postoperative residual rates, extents of tumors and resection of
      normal brain tissues after use of the three approaches in these patients were
      analyzed statistically. RESULTS: Septum pellucidum tumor is more likely to attack
      young or middle-aged persons. The tumor mainly presents itself as a central
      neurocytoma or cerebral low-grade glioma in pathology and manifests as
      intracranial hypertension clinically. No difference was found in the extent of
      tumor resection but significant difference in the extent of normal brain tissue
      resection and in postoperative disability rate among the three approaches. The
      transcortical approach brought about the most serious injury to brain tissue and
      the highest disability rate, Whereas the frontal transcallosal approach the
      lightest injury and the lowest disability rate. The injury to brain tissue and
      the disability rate brought about by the front trans-sulcus approach were between
      the above two approaches. CONCLUSIONS: Operation is still regarded the major
      treatment for septum pellucidum tumor. Transcallosal and trans-sulcus approaches
      are fit with the concept of minimally invasive surgery, and transcallosal
      approach is the first choice for septum pellucidum tumor.

PMID- 15989761
TI  - Effects and wavelet spectral entropy analysis of rhubarb extracts rhein on
      synaptic transmission in rat hippocampal ca1 area in vitro.
AB  - BACKGROUND: 5-dihydroxyanthraquinone-2-carboxylic acid (rhein) inhibits
      oxidoreduction induced by reducing nicotingamide adenine dinucleotide in the
      mitochondria and reducing reactive oxygen species, it also suppresses lipid
      peroxidation in rat brain homogenates. This study was to assess the effects of
      anthraquinone derivatives, rhein on synaptic transmission in the rat hippocampal
      CA1 pyramidal cell layer by intracellular recording. METHODS: The excitatory
      postsynaptic potential (EPSP) evoked by stimulation of the Schaffer collaterals
      in the presence of bicuculline (15 micromol/L) was depressed by application of
      rhein (0.3 - 30 micromol/L). The amplitude of the EPSP was restored within 20
      minutes after removal of rhein from the supernatant. At a concentration of 30
      micromol/L, rhein reduced the amplitude of the EPSP to 42% +/- 3.7% (n = 24) of
      the control. Subsequently, wavelet spectral entropy was used to analyze the EPSP.
      RESULTS: A strong positive correlation was observed between the wavelet spectral
      entropy and other parameters such as amplitude, slope of rising phase and slope
      of descending phase of the EPSP. The paired-pulse facilitation (PPF) of the EPSP
      was significantly increased by rhein (30 micromol/L). The inhibitory postsynaptic
      potential (IPSP) recorded in the presence of CNQX (20 micromol/L) and APV (40
      micromol/L) is not altered by rhein (30 micromol/L). CONCLUSIONS: Rhein (30
      micromol/L) can decrease the frequency but not the amplitude of the miniature
      EPSP (mEPSP). It is suggested that rhein inhibits excitatory synaptic
      transmission by decreasing the release of glutamate in rat hippocampal CA1
      pyramidal neurons.

PMID- 15989762
TI  - Localization and distribution of magnetic chemotherapeutic drugs with magnetic
      targeting in rat brain.
AB  - BACKGROUND: Magnetic targeting therapy may be a new method for the treatment of
      malignent tumors. The purpose of this study was to investigate the localization
      and distribution of ferrofluid microsphere of human serum albumin methotrexate
      (FM-HSA-MTX) carriers in the brain and to explore the magnetic targeting
      chemotherapy for malignant brain tumor. METHODS: Ninety SD rats were divided into
      three groups: targeting group, non-magnetic targeting group, and control group.
      Synthesized FM-HSA-MTX carriers (MTX 25 mg/kg) were injected into the systemic
      circulation via the caudal vein (magnetic targeting group, n = 30). A 0.6 T
      magnetic field was placed around the right hemisphere. The non-magnetic targeting
      group (n = 30) was administered with FM-HSA-MTX without external magnetic field,
      meanwhile the control group (n = 30) was treated with MTX and a magnetic field.
      Random serial sacrifices (n = 10) were conducted at 15, 30 and 45 minutes after
      drug administration. Bilateral hemispheres were collected respectively, and
      analyzed for total MTX content. RESULTS: MTX content in the right hemisphere of
      the magnetic targeting group was significantly higher than that in the other two
      groups at 15, 30 and 45 minutes after drug administration (P < 0.05) No
      difference was seen between the non-targeting group and control group. In the
      magnetic targeting group, MTX returned to the peak level [(0.564 +/- 0.018) mg/g,
      q15-45 = 32.252, P < 0.05] 45 minutes after the injection but it deceased in the
      other two groups [non-magnetic targeting group: (0.060 +/- 0.015) mg/g, q15-45 =
      9.245, P < 0.05, control group: (0.074 +/- 0.045) mg/g, q15-45 = 6.299, P <
      0.05]. In the magnetic targeting group, the concentration of MTX in the right
      hemisphere was significantly higher than that in the left hemisphere (t45min =
      21.135, P = 0.000) but no difference was observed between bilateral hemispheres
      in the other two groups (non-magnetic targeting group: t45min = 0.434, P = 0.670;
      control group: t45min = 0.533, P = 0.600). CONCLUSION: In the presence of the
      external magnetic field, FM-HSA-MTX can distribute successfully in the targeting
      areas of the brain.

PMID- 15989763
TI  - Microsurgical resection of tumors lateroventral and ventral to the high cervical
      spinal cord.
AB  - BACKGROUND: Since there are a complex anatomic structure and vital function in
      the high cervical spinal cord, it is difficult to remove the tumors lateroventral
      and ventral to the high cervical spinal cord. This clinical study was undertaken
      to analyze surgical approaches, manner of tumor resection and postoperative
      management. METHODS: Thirty-four patients underwent microsurgical excision of
      tumors lateroventral and ventral to the high cervical spinal cord by means of
      three approaches. The tumors comprised mostly Schwannoma and meningioma (88.24%,
      30/34) in this group. Tumor volume varied from 3.0 cm x 2.5 cm x 2.0 cm to 12 cm
      x 3.0 cm x 2.5 cm. Of the 34 patients, 4 had dumbbell-shaped tumors growing
      outside the spinal canal and 7 tumors growing into the intracranium. RESULTS: The
      tumor was totally removed in 32 patients (94.1%). Follow-up for 7 months to 6.4
      years (median 3.6 years) showed a recovery of a normal life or work ability in 30
      (83.3%) patients. CONCLUSION: Modified operative approaches and microsurgical
      techniques can raise the rate of total tumor removal and reduce the disability of
      patients.

PMID- 15989764
TI  - Microvascular decompression in patients with hemifacial spasm: report of 1200
      cases.
AB  - BACKGROUND: Microvascular Decompression (MVD) operation is the most reliable
      treatment for hemifacial spasm (HFS), but it causes many complications. The aim
      of this retrospective study was to investigate the factors relavent to the
      effects and postoperative complications of microvascular decompression on
      hemifacial spasm. METHODS: A total of 1200 HFS patients treated with MVD were
      studied retrospectively. The root exit zone (REZ) of the facial nerve was exposed
      through the infraflocculus approach, the offending vessels were identified and
      separated from the REZ, and a Teflon graft was interposed between the offending
      vessels and the brain stem. Brain stem auditory evoked potential (AEP) was
      monitored intraoperatively. RESULTS: The offending vessels can be identified in
      all patients. The anteroinferior cerebellar artery was the main offending vessel
      (42.6%). Patients with vertebral artery compression had a multiple vascular
      compression fashion. Follow-up for 2 - 10 years (mean 4.2 years) showed that
      88.7% patients were cured and 5.6% relieved, with an effective rate of 94.3%.
      Recurrence rate was 3.2%, and the ineffective rate was 2.6%. The most frequent
      complication was hearing dysfunction (2.8%). CONCLUSIONS: MVD is the most
      definitive treatment method of HFS. The key procedures of this operation include
      adequate exposure of the REZ, identification of the offending vessels, and proper
      positioning of Teflon grafts. Complications can be reduced effectively by
      utilizing a real-time AEP monitoring during the operation.

PMID- 15989765
TI  - Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland
      Chinese patients and clinical and molecular characterization of spinocerebellar
      ataxia type 6.
AB  - BACKGROUND: Dominantly inherited spinocerebellar ataxia (SCA) is a clinically and
      genetically heterogeneous group of neurodegenerative disorders. This study was to
      further assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2,
      SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7,
      SCA8, SCA10, SCA12, SCA14, SCA17 and DRPLA (dentatorubro-pallidoluysian atrophy)
      in mainland Chinese, and to specifically characterize mainland Chinese patients
      with SCA6 in terms of clinical and molecular features. METHODS: Using a molecular
      approach, we investigated SCA in 120 mainland Chinese families with dominantly
      inherited ataxias and in 60 mainland Chinese patients with sporadic ataxias.
      Clinical and molecular features of SCA6 were further characterized in 13 patients
      from 4 families. RESULTS: SCA3/MJD was the most common type of autosomal dominant
      SCA in mainland Chinese, accounting for 83 patients from 59 families (49.2%),
      followed by SCA2 [8 (6.7%)], SCA1 [7 (5.8%)], SCA6 [4 (3.3%)], SCA7 [1 (0.8%)],
      SCA8 (0%), SCA10 (0%), SCA12 (0%), SCA14 (0%), SCA17 (0%) and DRPLA (0%). The
      genes responsible for 41 (34.2%) of dominantly inherited SCA families remain to
      be determined. Among the 60 patients with sporadic ataxias in the present series,
      3 (5.0%) was found to harbor SCA3 mutations while none was found to harbor SCA6
      mutations. In the 4 families with SCA6, significant anticipation was found in the
      absence of genetic instability on transmission. CONCLUSION: A geographic cluster
      of families with SCA6 subtype was initially identified in a mainland Chinese
      population.

PMID- 15989766
TI  - Multi-slice CT angiography by triple-phase enhancement in preoperative evaluation
      of hepatocellular carcinoma.
AB  - BACKGROUND: Triple-phase enhancement of multi-slice computed tomography (MSCT)
      has markedly improved the diagnostic accuracy of hepatocellular carcinoma (HCC),
      and MSCT angiography (MSCTA) has been proved useful in detecting vascular anatomy
      noninvasively. This study aimed to explore the value of MSCTA by triple-phase
      enhancement in preoperative evaluation of HCC. METHODS: Fifty-six consecutive
      cases of primary HCC scheduled for resection were studied with MSCTA by triple
      phase enhancement. The raw data images were processed on a workstation for
      multiplanar reconstruction (MPR) and three-dimensional (3D) reconstruction. The
      findings after processing of the data were compared with those after surgery or
      intraoperative sonography. RESULTS: The false positive rate of MSCTA by triple
      phase enhancement was 10.1% and its false negative rate was 4.3% in detecting
      HCC. No significant difference was observed in MSCTA and surgery or
      intraoperative sonography in detecting vascular anatomy anomalies and pathologic
      variations, whereas significant difference was found in detecting bile duct
      invasion with MSCT compared to intraoperative sonography. CONCLUSIONS: MSCTA by
      triple-phase enhancement not only improves the detection of HCC, but also
      provides valuable preoperative information about hepatic vascular architecture
      and parenchyma. MSCTA by triple-phase enhancement is worthy of application as a
      non-invasive method in preoperative evaluation of HCC.

PMID- 15989767
TI  - A novel method for orthotopic testicular transplantation in rats.

PMID- 15989768
TI  - Relations of nuclear factor-kappa B activity in the kidney of children with
      primary nephrotic syndrome to clinical manifestations, pathological types, and
      urinary protein excretion.

PMID- 15989769
TI  - Immune response in Balb/c mice induced by recombinant spike protein of severe
      acute respiratory syndrome coronavirus.

PMID- 15989770
TI  - Severe vulgaris psoriatic patients with acute myelogenous leukaemia and
      resolution after allogeneic bone marrow transplantation/peripheral blood stem
      cell transplantation.

PMID- 15989771
TI  - Twenty-six patients with nonfunctional pheochromocytomas.

PMID- 15989772
TI  - Pregnancy and delivery after liver transplantation: the first successful case in
      China.

PMID- 15989773
TI  - Early-onset primary torsional dystonia in a 4-generation Chinese family with a
      mutation in the DYT1 gene.

PMID- 15989774
TI  - Pelvic compartment syndrome caused by retroperitoneal hematoma of pelvic
      fracture.

PMID- 15989776
TI  - [Expression of human CGT52TGT MBL mutant in CHO cells and analysis of the
      expression product].
AB  - AIM: To explore preliminarily the mechanisms of immunodeficiency resulted from
      the CGT52TGT point mutation of mannan-binding lectin(MBL) gene. METHODS: The MBL
      gene containing CGT52TGT point mutation was amplified from the plasmid pMBLm52 by
      PCR, and then inserted into the eukaryotic expression vector pcDNA4/HisMax C.
      After confirmed by DNA sequencing, the recombinant expression vector was
      transfected into Chinese-hamster ovary(CHO) cells by electroporation. Zeocin of
      800 mg/L had been used for 30 days to select electroporated CHO cells, and then
      200 mg/L for another 30 days to obtain stable transfectant. The expression of
      mRNA was analyzed by RT-PCR, the recombinant protein was purified from the
      culture supernatant by Ni-NTA agarose chromatography and analyzed by SDS-PAGE
      under nonreducing condition and Western blot. RESULTS: The cDNA fragment
      amplified from pMBLm52 plasmid by PCR was about 750 bp and the recombinant
      plasmid pcDNA4/HisMax C-MBLm52 was constructed and transfected into CHO cells.
      The expression product purified from the culture supernatant appeared mainly at
      the site of M(r) 60,000, indicating a much lower oligomerization level than that
      of the recombinant human wild MBL and human plasma-derived MBL. CONCLUSION: The
      CGT52TGT point mutation of MBL gene does not affect the secretion of its product,
      but a Cys introduced by the mutation could form another disulfide bond which may
      disrupt the structure of MBL molecule as well as its function.

PMID- 15989777
TI  - [Expression of Tim-3 in tumor tissue and its role in the induction of tumor
      immune tolerance].
AB  - AIM: To explore the role of T cell immunoglobulin- and mucin- domain containing
      molecule-3 (Tim-3) in the induction of tumor immune tolerance by investigating
      the expression of two types of Tim-3 at the early stage of tumorigenesis and the
      temporal-spatial relationship between the expression of Tim-3 and other immuno
      inhibitory genes in tumor. METHODS: By using semi-quantitative RT-PCR method, we
      investigated the expression of Tim-3, forkhead box P3 (Foxp3), cytotoxic T
      lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor
      receptor family-related receptor (GITR), TGF-beta, IL-10 and IFN-gamma at
      different time in tumor of tumor-bearing mice. Meanwhile, the growth of tumor was
      determined. RESULTS: At the early stage of tumorigenesis, sTim-3 was expressed
      before flTim-3 in tumor. When flTim-3 was expressed, the expression of sTim-3 was
      down-regulated. The expression of Foxp3, and GITR was simultaneous with that of
      flTim-3 and was up-regulated gradually with tumor growth. The expression of CTLA
      4 was earlier than that of flTim-3 and also up-regulated gradually. The
      expression of flTim-3 and Foxp3 was also consistent with each other in tissue
      distribution. The growth of tumor was postively correlated with the expression of
      flTim-3, Foxp3, and CTLA-4 and negatively with the expression of sTim-3.
      CONCLUSION: Along with the growth of tumor, immune tolerance was gradually
      established in tumor. flTim-3 but not sTim-3 may induce tumor immunological
      tolerance.

PMID- 15989778
TI  - [Construction of the eukaryotic expression vector pIRES2-EGFP-Axin and its
      expression in glioma cells].
AB  - AIM: To construct the eukaryotic expression vector pIRES2-EGFP-Axin, and to
      express Axin in C6 glioma cells. METHODS: The Axin gene was amplified by PCR
      using pCMV5-HA-Axin as a template, and confirmed by DNA sequencing. The
      eukaryotic expression vector pIRES2-EGFP-Axin was constructed by introducing Axin
      DNA fragment into the sites of Nhe I and Sal I of pIRES2-EGFP vector. The plasmid
      was transfected into the C6 cells using lipofectamine. The expressed EGFP was
      observed under fluorescent microscope and the Axin protein expression was
      detected by immunostaining using anti-Axin antibody. RESULTS: The eukaryotic
      expression vector pIRES2-EGFP-Axin was constructed and transfected successfully
      into C6 glioma cells. The green fluorescence of EGFP was observed in the plasma
      and nuclei of transfected cells, and Axin protein was only found in the plasma.
      CONCLUSION: The recombinant expression vector pIRES2-EGFP-Axin was constructed,
      and the EGFP and Axin gene could be co-expressed in the C6 cells. This study laid
      a foundation for the further research of the function of Axin in cell
      differentiation, growth and tumorigenesis.

PMID- 15989779
TI  - [The study on the relationship between the tumor-like proliferation of
      synoviocytes and the expression of c-myc and ODC genes in adjuvant arthritis
      rats].
AB  - AIM: To investigate the mechanism of the tumor-like proliferation of synoviocytes
      in adjuvant arthritis (AA) rats. METHODS: Wistar rats were randomly divided into
      2 groups, AA group and control group. Freund's complete adjuvant was injected
      into AA group rats to induce adjuvant arthritis. The knee synovial tissues of the
      rats were taken and synoviocytes were separated and cultured in vitro. The
      proliferation of cultured synoviocytes was measured by MTT colorimetry.
      Meanwhile, the mRNAs of C-myc and ODC genes in synovial tissues of the rats were
      detected by semi-quantitative RT-PCR. RESULTS: (1)Synoviocytes of AA rats
      proliferated more markedly than those of control rats (P<0.01), and exhibited a
      tumor-like proliferation. (2)The mRNAs of C-myc and ODC genes were obviously
      higher in synovial tissues of AA rats than those of control rats. CONCLUSION: The
      tumor-like proliferation of synoviocytes from AA rat joint might be related to
      the increased mRNAs of C-myc and ODC genes.

PMID- 15989780
TI  - [Expression and genetic immunization of hantaan virus G2 recombinant adenovirus].
AB  - AIM: To express hantaan virus(HTNV) envelope glycoprotein G(2) recombinant
      adenovirus(Adeno-G(2)) in vero E6 cells and explore its property of inducing
      immune response. METHODS: Vero E6 cells were infected with the HTNV Adeno-G(2)
      (100 MOI). The expression of Adeno-G(2) in the infected Vero E6 cells was
      detected by IFA. BALB/c mice were immunized with HTNV Adeno-G(2), then the immune
      response to Adeno-G(2) was tested by ELISA, microcell-culture neutralizing
      experiment and lymphocyte proliferation test (MTT colorimetry). RESULTS: IFA
      detection showed the expression of Adeno-G(2) in the infected Vero E6 cells. The
      titer of specific antibody was 1:40; The low-titer neutralization antibody was
      also detected. But the lymphocyte proliferation reaction was not notable.
      CONCLUSION: The HTNV Adeno-G(2) can stimulate BALB/c mice to develop specific
      humoral immune response instead of specific cell-mediated immunity. This study
      provides the experimental basis for the development of gene engineering vaccine
      of HFRS.

PMID- 15989781
TI  - [Effects of berberine on DNFB-induced delayed type hypersensitivity in mice].
AB  - AIM: To investigate the effect of berberine (Ber) on DNFB-induced delayed type
      hypersensitivity (DTH) and explore the mechanism of the immunosuppression effect
      of berberine. METHODS: BALB/c mice were divided into three groups: control group,
      DTH group, and Ber-treated DTH group. The DTH group was sensitized to DNFB by
      painting the shaved abdomen with DNFB dissolved in propanone/olive oil. The Ber
      treated DTH group was injected (i.p.) with berberine daily for 7 consecutive
      days, with the total dose of 30 mg/kg. The control group was treated with the
      solvent without DNFB. All mice were then challenged by painting 10 microL of 2
      g/L DNFB on the left ears. The weight of right and left ears was measured at 48 h
      after challenge. Histological changes of mouse auricles were observed under light
      microscopy. Violet crystal staining was used to determine the effect of Ber on
      adhesion of mouse splenic lymphocytes to extracellular matrix (ECM). Annexin-V
      staining was used to detect the apoptotic rate of the lymphocytes in the lymph
      nodes. RESULTS: The results of ear weighting showed that Ber significantly
      inhibited DTH reaction (P<0.05). Histological observation indicated Ber reduced
      markedly the infiltration of lymphocytes. The adhesion of T lymphocytes to ECM
      was also notably decreased by Ber treatment (P<0.05). There was no obvious
      difference in apoptotic rates of the lymphocytes among Ber-treated DTH group, DTH
      group and control group (P>0.05). CONCLUSION: Ber can significantly inhibit the
      DNFB-induced DTH in mice. The reduced adhesion between mouse T lymphocytes and
      ECM may be one of the mechanisms of suppression of DTH by Ber.

PMID- 15989782
TI  - [Expression and identification of F1 antigen of Y.pestis in Saccharomyces
      cerevisiae].
AB  - AIM: To construct the recombinant vector containing F1 gene caf1 of Y.pestis and
      express it in Saccharomyces cerevisiae. METHODS: F1 gene caf1 of Y.pestis was
      inserted into pHSS6-mTn-3xHA/lacZ plasmid to construct recombinant vector pHSS6
      mTn-3xHA/lacZ-caf1. The recombinant plasmid was linearized with Not I and then
      transformed into yeast cells by acetate lithium (LiAc) method. Positive
      recombinants were selected with uracil-lack medium. The expressed F1 antigen was
      identified by SDS-PAGE and Western blot. RESULTS: SDS-PAGE and Western blot
      analysis showed that F1 antigen was expressed in Saccharomyces cerevisiae.
      CONCLUSION: The recombinant vector pHSS6-mTn-3xHA/lacZ-caf1 has been constructed
      and expressed successfully in Saccharomyces cerevisiae. These results lay the
      foundation for preparing gene vaccine of Y.pestis which could be taken via
      alimentary tract pathway.

PMID- 15989783
TI  - [Prokaryotic expression of HPV 16 L1 gene and identification of its immune
      activity].
AB  - AIM: To express the major capsid protein of human papillomavirus type 16 L1(HPV
      16 L1) in E.coli and identify its immune activity. METHODS: The L1 gene of HPV 16
      was cloned into the expression vector pThioHisC. The recombinant expression
      vector was transformed into E.coli, and the HisC-L1 protein was expressed under
      IPTG induction. The fusion protein was characterized by SDS-PAGE and Western
      blot. RESULTS: The HPV16-L1 gene in plasmid pThioHisC was expressed in E.coli as
      a fusion protein with M(r) about 70,800. The fusion protein reacted specifically
      with antibodies against HPV16-L1. CONCLUSION: The HPV-16 L1 gene was expressed
      successfully in E.coli, which provides necessary basis for preparing HPV-16 L1
      vaccine in human.

PMID- 15989784
TI  - [Identification of proteins interacting with adaptor protein Bam32].
AB  - AIM: To study the role of adaptor protein Bam32 in B cell antigen receptor (BCR)
      signaling cascades. METHODS: Using full length Bam32 as bait, yeast two-hybrid
      technique was used to screen the protein that could interact with Bam32. The
      interaction was further confirmed by co-transfection of 293T cells and
      coimmunoprecipitation. RESULTS: Protein tyrosine kinase Lyn was one of the strong
      positive clones identified by the yeast two-hybrid screening. This interaction
      was further confirmed in 293T cells by co-transfection and coimmunoprecipitation.
      By using specific anti-phosphotyrosine antibody, it was found that Bam32 could be
      phosphorylated by Lyn. CONCLUSION: The interaction of Bam32 with Lyn leads to
      Bam32 phosphorylation, which might play an important role in activating
      downstream signaling molecules.

PMID- 15989785
TI  - [Construction of cblN/Zap and its down-regulating effect on TCRzeta protein in
      Jurkat cells].
AB  - AIM: To construct the chimeric cblN/Zap molecule, and to observe its effect on
      TCRzeta protein in pcDNA3.1(+)-cblN/Zab transfected Jurkat cells. METHODS: Total
      RNA of Jurkat cells were isolated and reversely transcribed into cDNA, which were
      used as templates to amplify Zap SH2 by PCR. cblN gene tagged with 24 bp flag was
      amplified by PCR using pEFHAcbl plasmid encoding human cbl as templates. BamH I
      and EcoR V restriction enzyme digestion sites were introduced into flank SH2 in
      pcDNA3.1(+) cblN by overlapping extension PCR. Then pcDNA3.1(+)-cblN/Zap was
      obtained by replacing SH2 of cblN with ZapSH2. After confirmation by enzyme
      digestion and sequencing, the recombined vector was stably transfected into
      Jurkat cells with lipofectin. The expression of flag-cblN/Zap was detected by RT
      PCR and Western blot, and its effect on TCRzeta protein was analyzed by Western
      blot. RESULTS: Restriction enzyme digestion analysis of the pcDNA3.1(+)-cblN/Zap
      recombinant vector showed that the expected fragments were produced and confirmed
      by sequencing. pcDNA3.1(+)-cblN/Zap was stably transfected into Jurkat cells and
      the expression of flag-cblN/Zap in the stable clones was confirmed by both RT-PCR
      and Western blot. The expressed cblN/Zap down-regulated TCRzeta protein in Jurkat
      cells. CONCLUSION: Chimeric cblN/Zap is able to down-regulate TCRzeta in Jurkat
      cells.

PMID- 15989786
TI  - [The effect of retinoic acid on C3 and factor B secretion of human alveolar type
      II epithelial cells induced with cytokines].
AB  - AIM: To explore the effect of retinoic acid (RA)on C3 and factor B (Bf) secretion
      by human alveolar type II epithelial cell line A549 induced with cytokines.
      METHODS: The levels of C3 and Bf in culture supernatant of A549 cells induced
      with cytokines were detected by ELISA. The expression of C3 and Bf mRNAs was
      analyzed by RT-PCR. RESULTS: TNF-alpha, IL-1beta, IL-6 and IFN-gamma could induce
      the secretion of C3 and Bf of A549 cells. RA alone had no effect on secretion of
      C3 and Bf of A549 cells but could notably enhance the secretion of C3 and Bf of
      A549 cells induced by the cytokines. CONCLUSION: RA can up-regulate the
      expression of C3 and Bf of A549 cells induced with TNF-alpha, IL-1beta, IL-6 and
      IFN-gamma, and regulate the immunological defence of local lung tissue, which
      provides a theoretical basis for prevention and treatment of pulmonary diseases
      by using RA and cytokines.

PMID- 15989787
TI  - [Improving the affinity of an anti-TNF-alpha scFv by random mutation].
AB  - AIM: To improve the affinity of an anti-TNF-alpha scFv. METHODS: A mutant phage
      antibody library derived from an anti-TNF-alpha scFv gene was generated by error
      prone PCR. The mutated genes were then subjected to DNA shuffling. Mutants with
      improved affinity were selected by bio-panning. Affinity improvement of the
      selected mutants was verified by dot blot ELISA and thiocyanate elusion ELISA.
      RESULTS: One mutant was obtained with relative affinity index (1.37 mol/L) higher
      than that of the parent scFv (0.48 mol/L). CONCLUSION: Error-prone PCR plus DNA
      shuffling is effective in improving the affinity of antibodies.

PMID- 15989788
TI  - [Construction of a large human scFv library against SARS virus].
AB  - AIM: To construct a large human scFv library against SARS virus by using in vivo
      recombination. METHODS: Total RNA was isolated from the lymphocytes of 6 patients
      recovered from SARS. mRNA was isolated and reverse transcribed into cDNA. The
      V(H) and V(L) fragments were amplified from the cDNA and then assembled into scFv
      genes. The scFv genes were amplified and ligated into phagemid pDAN5. The primary
      library was constructed by transforming the recombinant phagemid into E.coli TG1.
      The secondary library was generated by in vivo recombination in E.coli BS1365
      following the infection of BS1365 by primary library phages. RESULTS: A primary
      library of 3x10(9) and a second library of 3x10(11) were constructed. CONCLUSION:
      A large human scFv library against SARS virus with good diversity was
      constructed, which may be used for screening antibodies to SARS virus antigens.

PMID- 15989789
TI  - [Screening the antibody mimic peptide binding to hepatocellular carcinoma cells
      by phage display technique].
AB  - AIM: To screen the antibibody mimic peptide binding to hepatocellular carcinoma
      (HCC) from the circular 7-mer peptide libraries. METHODS: The enrichment of phage
      was achieved by repetitious biopanning. The affinity of peptide was evaluated by
      ELISA, and the binding site of the peptide was analysed by the competition ELISA.
      RESULTS: The output of phage gradually rose along with increasing of biopanning
      times. The obtained circular 7-mer peptide showed good binding activity to
      hepatocellular carcinoma cell lines SMMC-7721 and BEL-7402 (P<0.05), and its
      affinity to SMMC-7721 cells was superior to that of BEL-7402 (P<0.05). At the
      level of alpha=0.01, the screened 7-mer peptide monoclonal stocks could obviously
      compete with scFv to bind SMMC-7721 cells (0.005<P<0.01). As the concentration of
      scFv gradually fell, the competition inhibition rate dropped accordingly.
      Sequence analysis showed that the sequences of 7-mer positive monoclonal stocks
      were identical. CONCLUSION: The peptide obtained through biopanning was specific
      and effective, which may provide further support for target therapy of HCC.

PMID- 15989790
TI  - [Prokaryotic expression of DnaJ-homologous chaperon PBP and preparation of rabbit
      antibody against PBP].
AB  - AIM: To express DnaJ-homologous chaperon peripherin-binding protein(PBP) gene in
      E.coli and prepare the rabbit antibody against PBP. METHODS: The PBP cDNA was
      amplified from the human fetal brain tissue by RT-PCR. After confirmed by DNA
      sequencing, the PBP-cDNA was cloned into expression vector pET28a and then the
      PBP gene was expressed in E.coli under the IPTG induction. The expressed protein
      was purified through Ni-NTA affinity chromatography column. The rabbit antibody
      against PBP was prepared by immunizing two New Zealand white rabbits using the
      purified PBP as immunogen. The titer and specificity of the antisera were
      determined by Western blot. RESULTS: The 720 bp PBP gene was amplified, cloned,
      and expressed in E.coli. The expressed product existed in the bacterial inclusion
      body and the supernatant of the bacteria lysate. The purified PBP reached
      electrophoretic purity. The rabbit antibody against PBP was prepared and its
      titer was about 1:1,600. Western blot analysis showed that the antibody could
      bind to the expressed PBP protein specifically. CONCLUSION: The PBP protein was
      expressed in E.coli and rabbit antibody against PBP was prepared successfully,
      which lays the foundation for further study on the structure and biological
      function of PBP.

PMID- 15989791
TI  - [Expression of a candidate human Era binding protein A19 and the preparation of
      its polyclonal antibody].
AB  - AIM: To express a candidate hEra binding protein A19 in Escherichia coli and to
      prepare anti-A19 antibody. METHODS: A19 gene was amplified by PCR from the
      plasmid containing A19 gene and was cloned into the expression vector pGEX-4T3
      which was then transformed into E.coli. The A19 protein was expressed under IPTG
      induction. Antiserum was prepared by immunizing rabbits with the expressed A19
      protein. The titer and specificity of polyclonal antibody were detected by
      Western blot. RESULTS: The expressed A19 accounted for about 30.2% of total
      bacterial protein. The titer of the antiserum was about 1:4 000. Western blot
      analysis indicated that the antiserum had high specificity. CONCLUSION: A19
      fusion protein was highly expressed. The specific anti-A19 antiserum was prepared
      successfully.

PMID- 15989792
TI  - [Prokaryotic expression of human cTnI and preparation of rabbit anti-hcTnI
      antibody].
AB  - AIM: To construct the prokaryotic expression vector pET-21a(+)-hcTnI and prepare
      the rabbit anti-hcTnI antibody using hcTnI expressed in E.coli as immunogen.
      METHODS: The full-length gene encoding human cardiac troponin I (hcTnI) was
      synthesized chemically and inserted into expression plasmid pET-21a(+) to
      construct recombinant plasmid pET-21a(+)-hcTnI. The recombinant plasmid was
      transformed into E.coli BL21 (DE3) plysS which then expressed hcTnI under IPTG
      induction. The immunological activity of the expressed hcTnI was analyzed by
      Western blot. A rabbit was immunized with purified hcTnI to prepare anti-hcTnI
      antibody and the Ab's properties were identified. RESULTS: Human cTnI gene was
      synthesized and confirmed by DNA sequencing. Positive recombinant clones were
      identified by restriction enzyme digestion analysis and DNA sequencing. After
      induction with IPTG, hcTnI with M(r) being 24 000 was expressed in E.coli BL21
      (DE3) plysS, and the expressed hcTnI accounted for 28% of total bacterial
      protein. Western blot analysis showed that the hcTnI protein could be recognized
      by an anti-hcTnI antibody. Rabbit polyclonal antibody with a good specificity was
      obtained. The titer of the polyclonal antibody was 3x10(-4). CONCLUSION: The
      recombinant expression plasmid of hcTnI was constructed successfully and
      expressed in E.coli. The prepared rabbit anti-hcTnI antibody had a high titer and
      specificity.

PMID- 15989793
TI  - [Cloning of variable region and signal peptide genes of anti-CD20 monoclonal
      antibody by RLM-RACE].
AB  - AIM: To seek a good method for simultaneous cloning V(L), V(H) and signal peptide
      genes of anti-CD20 monoclonal antibody (mAb) from hybridoma cells 1-28. METHODS:
      Total RNA was prepared from hybridoma cells 1-28 by Trizol. Two methods were used
      to clone the target genes. One was traditional rapid amplification of 5' cDNA end
      (T-5' RACE), and the other was RNA ligase-mediated rapid amplification of 5' cDNA
      end (RLM-RACE). The PCR products were then cloned into pGEM-T Easy vector,
      sequenced and analyzed with Blast method using Kabat and GenBank Databases.
      RESULTS: The target genes of L chain and H chain were both successfully cloned by
      RLM-RACE, while only V(L) gene and its signal peptide genes were obtained by T-5'
      RACE. CONCLUSION: RLM-RACE is a good method for cloning antibody's V gene and
      signal peptide genes.

PMID- 15989794
TI  - [Construction and expression of scFv phage antibody from natural anti-keratin
      monoclonal antibody 3B4].
AB  - AIM: To construct and express the scFv phage antibody from natural anti-keratin
      monoclonal antibody 3B4 in E.coli and then compare its antigenic specificity with
      that of the parental antibody 3B4. METHODS: The V(H) and V(L) of 3B4 were
      amplified by PCR from pMD-18T- mAb 3B4 V(H) and pMD-18T- mAb 3B4 V(L), and then
      cloned into the phagemid pscMH. E.coli was transfected by recombined pscMH and
      superinfected by the helper phage VCSM13. Then the antigenic specificity of the
      scFv concentrated from the supernatant of the transfected E.coli was detected by
      indirect ELISA. RESULTS: DNA sequence analysis showed that the scFv sequence was
      the same as the original sequence except that there was one base mutation in the
      FR1 of V(L). Indirect ELISA showed that the scFv phage antibody was polyreactive
      as mAb 3B4, but its antigenic specificity was not the same with that of mAb 3B4.
      CONCLUSION: The scFv phage antibody from natural anti-keratin monoclonal antibody
      3B4 was successfully constructed and expressed. Its antigenic specificity was
      different from that of its parental antibody 3B4.

PMID- 15989795
TI  - [Preparation and characterization of non-agglutinating mAbs against membrane
      antigen on human erythrocytes].
AB  - AIM: To prepare monoclonal antibodies (mAbs) against membrane antigens on human
      erythrocytes and characterize their properties. METHODS: BALB/c mice were
      immunized with the membrane antigens of human type O erythrocytes. The
      splenocytes of the immunized mice were fused with Sp2/0 myeloma cells by
      hybridoma technique. The antibodies to common antigen on human erythrocytes were
      screened by hexadimethrine bromide (polybrene) test tube method and then the
      agglutinating antibodies (complete antibodies) were weeded out by slide
      hemagglutination assay. The hybridoma cells secreting non-agglutinating
      antibodies (incomplete antibodies) were cloned by limiting dilution method. The
      stability of the obtained hybridoma cells and the properties of the mAbs were
      identified. RESULTS: One hybridoma cell 2E8 was obtained, which secreted non
      agglutinating antibody. The mAb 2E8 belonged to IgG1, could agglutinate H
      antigen, and had no species cross-agglutination reaction. The titers of culture
      supernatant and ascites of 2E8 were 1:1,024 and 1:64x10(6), respectively. When
      the affinity of mAb 2E8 was evaluated by agglutination reaction, erythrocytes
      began to agglutinate after 7 seconds and the clots exceeded 1 mm(2) in 3 minutes.
      CONCLUSION: The non-agglutinating mAb against H antigen was prepared
      successfully. The mAb 2E8 has good titer, affinity and specificity, which lays
      the foundation for preparation of bispecific antibodies (BsAb).

PMID- 15989796
TI  - [Preparation of polyclonal and monoclonal antibodies against CRF and change of
      CRF in the sleep-deprived rat brain].
AB  - AIM: To produce polyclonal and monoclonal antibodies against corticotropin
      releasing factor (CRF) and to study the changes of CRF in sleep-deprived rat
      brain with the antibodies acquired. METHODS: Commercial CRF was linked to bovine
      throglobulin (BTG) and bovine serum albumin (BSA) respectively to produce
      immunogen and embedding antigen. New Zealand rabbits and BALB/c mice were
      immunized with the BTG-CRF immunogen to produce polyclonal and monoclonal
      antibodies, respectively. The acquired antibodies were appraised with ELISA and
      immnohistochemical staining. The characterized antibodies were used to observe
      the changes of CRF in the rat brain 48 h after sleep deprivation. RESULTS: CRF
      polyclonal antibody and 9 clones of monoclonal antibodies were obtained with high
      titer, affinity and specificity. Among them, the polyclonal antibody and 2
      monoclonal antibodies (1D10, 2F4) were excellent in immunocytochemical staining.
      The CRF-like immunoreactive substances were found more strongly expressed in the
      neurons of paraverticular hypothalamic nucleus (PVN), central subnucleus of
      amygdala (CeA), oval subnucleus of bed nucleus of stria terminalis (BNSTov), and
      nucleus of solitary tract (NTS) in sleep-deprived rat brain. While they were much
      weaker and even absent in the control. CONCLUSION: The polyclonal and monoclonal
      antibodies against CRF were successfully produced for immunocytochemical studies.
      The results indicate that CRF may play an important role in stress-responsive
      modulation during sleep deprivation. PVN, CeA and BNSTov are integral part of
      brain circuit related to the stress modulation.

PMID- 15989797
TI  - [Exploration of mechanisms underlying T-cell anergy induced by immunotherapy in
      allergic murine asthma model].
AB  - AIM: To explore the mechanisms underlying the T cell anergy induced by
      immunotherapy for the treatment of allergic asthma. METHODS: Murine model of
      allergic asthma was established through the OVA sensitization and challenge.
      Three injections of 1 mg OVA were used as immunotherapy. Pathological examination
      of lung tissues, cell count and differential count of bronchoalveolar lavage
      fluid (BALF), determination of serum OVA-specific IgE, and measurement of IL-2
      and IL-4 production and proliferation of the splenic T cells to OVA were
      preformed to analyze the effect of immunotherapy on asthma. The expression of
      CTLA-4 on splenic T cells was detected by FACS. RESULTS: Asthma-specific
      immunotherapy could alleviate lung inflammation, decrease eosinophil infiltration
      in BALF (P<0.01) and serum OVA-specific IgE, inhibit the production of IL-2 and
      IL-4 and the proliferation of splenic T cells to OVA (P<0.01), and up-regulate
      the expression of CTLA-4 on splenic T cells. CONCLUSION: The up-regulation of
      CTLA-4 expression on T cells may be involved in the T cell anergy induced by
      asthma-specific immunotherapy.

PMID- 15989798
TI  - [Relationship between glomerular lesion and NF-kappaB p65 activity in rat
      multiple organ failure caused by zymosan].
AB  - AIM: To observe the relationship between NF-kappaB p65 activity and glomerular
      lesion in rat multiple organ failure (MOF) caused by zymosan. METHODS: Twenty
      female Wistar rats aged 6-8 weeks were divided randomly into two groups, ten each
      group. 24 hours after MOF model was induced successfully by intraperitoneal
      injection of zymosan-paraffin oil suspension, the rats were sacrificed and the
      functions of liver and kidney as well as blood gas were analysed. At the meaning
      time, the pathological change in renal tissues was examined by H.E, PAS, PASM and
      Masson staining, whereas the NF-kappaB p65 activity in glomeruli was detected by
      immunohistochemical staining and ELISA. RESULTS: The levels of PO(2) and pH in
      blood of MOF model group were significantly lower than those of control group,
      while the levels of serum ALT and Cr were quite to the contrary. Pathological
      examination showed that in MOF model rats, there were notable proliferation of
      glomeruli, partial sclerotic glomeruli and a large number of infiltrating
      inflammatory cells in glomeruli and periglomeruli. Besides, the activity of NF
      kappaB p65 in rat glomeruli of MOF model group was significantly higher than that
      of control group(P<0.01), and the increased activity of NF-kappaB p65 was
      positively corelated to the cell number in glomeruli, and area density of
      basement membrane as well as mesangial area, but negatively correlated to the
      area density of capillary loop. CONCLUSION: The increase in the activity of NF
      kappaB p65 may play an important role in glomerular lesions of MOF model rats
      caused by zymosan.

PMID- 15989799
TI  - [Detection of expression of endometriosis-related cytokine and their receptor
      genes by cDNA microarray technique].
AB  - AIM: To study the pathogenesis of endometriosis(EM) by investigating cytokine(CK)
      and CKR genes expression involved in the development of EM. METHODS: The CK and
      CKR gene expression pattern in samples of EM and normal endometrial tissues were
      analyzed by using cDNA microarrays. RESULTS: 119 genes were expressed differently
      between 3 cases EM tissues and 3 cases normal endometria tissues. Among them, 15
      were CK and CKR genes, including IL-1, IL-2, IL-6, IL-8, VEGFR, TGF, EGF, FGF,
      and EPOR etc. CONCLUSION: These 15 differently expressed CK and CKR genes may be
      correlated with the development of EM.

PMID- 15989800
TI  - [Induction of specific immunity against tumor endothelial cells by dendritic
      cells in vitro].
AB  - AIM: To study the specific cytotoxicity of cytotoxic T lymphocytes(CTLs) induced
      by dendritic cells(DCs) loaded with tumor-derived endothelial cells (Td-ECs)
      antigen. METHODS: Td-ECs were generated from human umbilical vein endothelial
      cells (HUVECs) by induction with cultured supernatants of tumor cells. The
      expression of tumor endothelial marker(TEM) was detected by RT-PCR. Human
      peripheral blood monocyte-derived DCs were loaded with Td-EC freeze-thawing
      antigen, and the autologous stimulation capacity of DCs was determined via mixed
      lymphocytes reaction employing MTS colorimetry. Specific cytolytic activity of
      CTLs induced by DCs was assessed by lactate dehydrogenase(LDH) assay. RESULTS:
      TEM1 and TEM8 were detected only on Td-ECs. DCs loaded with Td-EC antigen
      stimulated lymphocytes proliferation significantly. CTLs induced by DCs loaded
      with Td-EC antigen showed higher cytolytic activity against Td-EC than that of
      the control groups (33% vs 14% at E/T ratio 20, 27% vs 10% at E/T ratio 10).
      CONCLUSION: DC loaded with Td-EC antigen can effectively induce specific CTLs
      against Td-ECs in vitro.

PMID- 15989801
TI  - [Study on the surface markers on peripheral blood dendritic cells and their
      secretion of IL-12 and IFN-alpha in SLE patients].
AB  - AIM: To analyze the surface markers on peripheral blood dendritic cells (DCs) in
      SLE patients and explore the relationship between the DCs and pathogenesis of
      SLE. METHODS: The peripheral blood monouclear cells (PBMCs) were separated by
      density gradient centrifugation. After culture of 3 hours in tissue culture
      flask, the suspended cells were removed and GM-CSF, IL-4 and TNF-alpha were used
      to stimulate the proliferation and maturation of the peripheral blood DCs from
      normal persons and SLE patients. The surface markers on the DCs were analyzed by
      flow cytometry and the levels of IL-12 and IFN-alpha in supernatants were
      measured by ELISA after culture of 9 days. RESULTS: The positive percentages of
      CD1a, CD11c, CD40, CD83 and CD123 expressed on DCs of SLE patients were (58.88+/
      7.64)%, (54.4+/-10.88)%, (37.29+/-8.08)%, (57.76+/-11.54)% and (13.14+/-4.44)%,
      respectively, whereas those of normal subjects were (47.71+/-4.01)%, (43.12+/
      8.82)%, (28.59+/-7.07)%, (48.31+/-8.79)% and (9.85+/-3.97)%, respectively,
      (P<0.05). But the positive proportion of CD80 expression was (55.16+/-10.12)% in
      SLE group and (47.95+/-12.21)% in the control group, without significant
      difference (P>0.05). The level of IL-12 in SLE group was (9.78+/-0.76) ng/L,
      higher than that in normal group. The level of IFN-alpha in SLE group (2.95+/
      0.61) ng/L was not significant difference from that in control group (2.70+/
      0.29) ng/L (P>0.05). And there was no significant difference in IL-12 and IFN
      alpha levels between non-active and active stages of SLE patients. CONCLUSION:
      The DCs may be involved in the pathogenetic process of SLE possibly by means of
      enhancement of antigen presenting function of DCs and secretion of IL-12.

PMID- 15989802
TI  - [The relationship between Helicobacter pylori infection and IL-8 expression in
      remnant stomach mucosa].
AB  - AIM: To explore the relationship between helicobacter pylori (Hp) infection and
      expression of interleukin-8 (IL-8) in the remnant stomach mucosa. METHODS: Fifty
      eight patients with gastrectomy were examined by upper gastrointestinal
      endoscopy. Biopsy specimens were obtained from stoma and the greater curvature of
      the upper corpus to detect Hp infection (by H.E. and Giemsa staining) and IL-8
      expression (by real-time semi-quantitative RT-PCR). RESULTS: Hp infection was
      detected in 65.5% (38/58)of the remnant stomach mucosa. In 34 patients with
      Billroth I (BI) anastomosis, IL-8 in corpus was significantly higher in Hp
      positive patients than that in Hp-negative patients (0.11+/-0.07 vs 0.02+/-0.01,
      P<0.05). In 24 patients with Billroth II (BII) anastomosis, IL-8 in stoma and
      corpus in Hp-positive patients was significantly higher than that in Hp-negative
      patients (P<0.05). CONCLUSION: Hp infection induces IL-8 expression in remnant
      stomach mucosa. In corpus, IL-8 mRNA expression is mainly related with Hp
      infection, while in stoma, IL-8 mRNA expressions may be related with bile reflux
      besides Hp infection.

PMID- 15989803
TI  - [Evaluation of IL-6 level in serum and bronchoalveolar lavage fluid of patients
      with non-small cell lung cancer (NSCLC)].
AB  - AIM: To study the relationship between the interleukin-6(IL-6) level in serum and
      broncheoalveolar lavage fluid(BALF) and non-small cell lung cancer(NSCLC).
      METHODS: The concentration of IL-6 in serum or BALF of 62 NSCLC patients, 36
      patients of pulmonary inflammatory diseases (PID) and 25 normal controls were
      measured by ELISA. RESULTS: (1)The concentration of IL-6 in BALF of NSCLC
      patients was significantly higher than that of PID patients and normal controls
      (P<0.01). The concentration of IL-6 in sera of NSCLC patients was higher than
      that of normal controls (P<0.01) but not statistically different from that of PID
      patients. (2)In patients with NSCLC, the concentration of IL-6 in BALF was
      slightly higher than that of serum IL-6, but this difference was not
      statistically significant (P>0.05). (3)Serum IL-6 level was higher in NSCLC of
      advanced stages (stage IIIa, IIIb and IV), as compared with that in NSCLC
      patients of early stages (stage Ia-IIb). BALF IL-6 level of NSCLC patients at
      different stages was not different. (4)IL-6 (level in serum but not in BALF) of
      PID patients correlated with the serum concentration of C reactive protein
      (r=0.74). CONCLUSION: IL-6 in BALF might be used as a marker for NSCLC. Serum IL
      6 level might be an indicator for the stage of NSCLC. The serum IL-6 can also
      reflect the severity of acute lung inflammatory response.

PMID- 15989804
TI  - [Relationship between the amount of nitric oxide and apoptosis of germ cells in
      the semen of infertile men].
AB  - AIM: To explore the relationship between nitric oxide(NO) and apoptosis of germ
      cells in the semen of infertile men. METHODS: Copper-coated cadmium reduction
      fluorescence assay was used to detect nitrate, the metabolic product of NO. The
      apoptosis and ultrastructure of germ cells were detected and observed by TdT
      mediated dUTP nick end labeling (TUNEL) and transmission electronls microscope
      (TEM), respectively. RESULTS: In normal control group, concentration of NO and
      the apoptotic rate of germ cells were (56.83+/-11.65) micromol/L and (4.60+/
      1.25)%, respectively; while in inferile group were (128.86+/-23.76) micromol/L
      and (17.36+/-3.05)%, respectively. The differences in NO concentration and the
      apoptotic rate of germ cells between the two groups were significant (P<0.01).
      The concentration of NO was positively correlated with the apoptotic rate of germ
      cells in infertile group (r=0.96). The apoptotic germ cells showed typical
      morphology of apoptosis, including nuclear chromatin condensation and
      margination, nuclear memberane folding, and formation of apoptotic bodies.
      CONCLUSION: The amount of NO in semen from infertile men has close relationship
      with apoptotic rate of germ cells. High concentration of NO may result in the
      increase of germ cell apoptosis rate and lead to male infertility.

PMID- 15989805
TI  - [Expression and nuclease activity analysis of staphylococcus nuclease in E.coli].
AB  - AIM: To express staphylococcus nuclease (SN) in E.coli and prepare rabbit
      antisera against SN. METHODS: The SN gene was amplified by high-fidelity PCR from
      plasmid pPLC-SN and then subcloned into expression vector pLEX to obtain the
      recombinant plasmid pLEX-SN. The expression of recombinant protein was induced by
      tryptophan. The expressed SN was used to immunize a rabbit to prepare specific
      antibody. RESULTS: SDS-PAGE analysis showed that the relative molecular mass
      (M(r)) of the expressed SN was about 17,000 and the expressed SN accounted for
      about 37% of total bacterial proteins. The prepared antisera were specific to
      react with recombinant SN. CONCLUSION: Expression vector of SN has been
      successfully constructed and rabbit antibody against SN was prepared. These
      results lay the foundation for developing SN as antiviral protein.

PMID- 15989806
TI  - [Exploration of ganglioside GM1 as an activation marker on T cells].
AB  - AIM: To compare and analyze the patterns of ganglioside GM1 and CD69 expressions
      on activated gammadeltaT cells and CD3(+) T cells from human peripheral blood.
      METHODS: PBMCs were stimulated in vitro with anti-CD3 mAb or Mycobacterium
      tuberculosis antigen (Mtb-Ag). In some experimental groups, PBMCs were pretreated
      with different inhibitors of signal transduction pathway before stimulation. The
      expressions of GM1 or CD69 on gammadeltaT and CD3(+) T cells at different time
      points after stimulation were measured by flow cytometry (FCM). RESULTS: GM1
      appeared on gammadeltaT cells at 30 min after stimulation with Mtb-Ag and
      retained a higher level with the lapse of time; whereas CD69 expression appeared
      at 3 h after stimulation and reached peak at 24 h, and then decreased gradually
      to the resting level on day 6 after stimulation. The expressions of CD69 and GM1
      on CD3(+) T cells stimulated with anti-CD3 mAb were similar to those on
      gammadeltaT cells. The expression of GM1 on gammadeltaT cells was inhibited by
      pretreatment with PD98059 or LY294002. PMA increased the expression of GM1.
      CONCLUSION: GM1 can serve as a novel marker of activated T cells. During the
      activation of T cells, the dynamic expression of GM1 was different from that of
      CD69, a very early activation antigen. The Ras-Erk signal transduction pathway
      and PI3K and PKC might be involved in the expression of GM1.

PMID- 15989807
TI  - [Histamine release properties of human basophils in response to various stimuli].
AB  - AIM: To investigate the effects of protease activated receptor-2 (PAR-2) agonist,
      heparin and other stimuli on histamine release from human basophils. METHODS:
      Peripheral blood mononuclear cells (PBMCs) were separated by density gradient
      centrifugation. The PBMCs were then resuspended in complete Hank's balanced salt
      solution (HBSS) and challenged with various stimulating agents. Histamine level
      in samples was determined by ELISA. RESULTS: 10 mg/L trypsin could induce
      histamine release from basophils. However, its stimulatory effect on basophils
      was weaker than that of anti-IgE, calcium ionophore (CI), F-Met-Leu-Phe (FMLP),
      C5a and substance P. PAR-2 agonist SLIGKV-NH(2) failed to activate basophils.
      Heparin, C5 and adenosine did not induce any histamine release at concentrations
      tested, but heparin enhanced histamine release induced by C5a and substance P.
      CONCLUSION: Trypsin, anti-IgE, CI, FMLP, C5a and substance P can induce histamine
      release from baosophils, but PAR-2 agonist can not. Heparin can greatly enhance
      the ability of C5a and substance P to stimulate histamine release, which may be a
      novel mechanism of amplification of basophil activation signal.

PMID- 15989808
TI  - [Study on apoptosis of human cervical carcinoma HeLa cells with RNA interference
      targeting hTERT].
AB  - AIM: To study the induction of tumor cell apoptosis by RNA interference-mediated
      inhibition of the expression of telomerase in cancer cells. METHODS: HeLa cells
      were transfected with the successfully established siRNA(small interfering RNA)
      expression vectors targeting hTERT (human telomerase reverse transcriptase). By
      electronic microscopy, Western blot and FCM (flow cytometry), the apoptosis of
      HeLa cells was tested. RESULTS: The established siRNA expression vectors could
      induce apoptosis of HeLa cells. CONCLUSION: Transfection of siRNA expression
      vectors targeting hTERT can induce apoptosis of HeLa cells.

PMID- 15989809
TI  - [Mechanism of apoptin-induced apoptosis of human lymphoma cells U937].
AB  - AIM: To study the role of c-Jun N-terminal kinase (JNK) in the apoptosis induced
      by apoptin gene in human lymphoma cell U937. METHODS: The U937 cells were
      transiently transfected by pcDNAA3 plasmids containing apoptin gene. Apoptosis of
      U937 cells was measured by flow-cytometry. Activation of JNK signal pathway was
      detected by Western blot. RESULTS: Apoptin could induce apoptosis of U937 cells
      in vitro at 48 h after transfection. The level of phosphorylated JNK was
      increased at 24 h and reached the peak level at 48 h after transfection.
      CONCLUSION: Apoptin gene can induce apoptosis of U937 cells in which JNK signal
      pathway plays an important role.

PMID- 15989810
TI  - [Manometric factors associated with recurrence in botulinum toxin treatment for
      chronic anal fissure].
AB  - INTRODUCTION AND AIM: To evaluate the effectiveness of botulinum toxin in the
      treatment of chronic anal fissure after long-term follow-up and establish the
      manometric factors related to recurrence. PATIENTS AND METHOD: We performed a
      prospective study in 50 consecutive patients with chronic anal fissure who were
      treated with 25 U botulinum toxin injected into the internal sphincter. Clinical
      and manometric parameters were recorded until the fourth year of follow-up.
      RESULTS: There was a tendency to progressive recurrence over time (54% at 4
      years) associated with manometric factors indicating hyperexcitability of the
      internal anal sphincter (persistently elevated mean resting pressure, percentage
      of time with slow waves, and number of patients or percentage of time with ultra
      slow waves after treatment). CONCLUSIONS: Treatment of chronic anal fissure with
      botulinum toxin leads to long-term cure in less than 50% of patients. In patients
      with manometric factors related to recurrence, this treatment is insufficient for
      definitive cure.

PMID- 15989811
TI  - [Study of gastronitestinal transit times with capsule endoscopy].
AB  - INTRODUCTION: Until the introduction of capsule endoscopy (CE), studies of
      gastrointestinal transit times were based on indirect data or data obtained with
      radiographic techniques. We analyzed gastric and intestinal transit times through
      the images obtained with EC and evaluated the influence of age, sex, body mass
      index (BMI) and abdominal perimeter on these times. PATIENTS AND METHOD: Of the
      total number of procedures performed over one year, we reviewed 89 in which CE
      reached the blind gut. Transit times through the pylorus and the ileocecal valve,
      as well as a series of clinical and epidemiological characteristics of the
      patients, were recorded. RESULTS: The mean age of the patients was 59.2 years
      with a mean BMI of 25.5. Gastric transit times ranged from 0.7 to 171 min (mean
      22.6) while small intestine transit times ranged from 91 to 416 min (mean 283.3).
      No significant associations were found between gastric and intestinal transit
      times with age, sex, BMI, or abdominal perimeter. A significant negative
      correlation (p < 0.05) was found between transit time of CE through the stomach
      with respect to the time taken between the pylorus and the cecal pole.
      CONCLUSION: CE is a good method to study gastrointestinal transit times directly
      and could lead to greater knowledge of the pathogenesis of various
      gastrointestinal entities. Age, sex and nutritional status do not seem to
      influence intestinal kinetics. In contrast, longer or shorter gastric emptying
      times have an inverse effect on the transit of CE through the small intestine.

PMID- 15989812
TI  - [Clinical heterogeneity and distinct outcomes in hepatic epithelioid
      hemangioendothelioma].
AB  - Epithelioid hemangioendothelioma is an infrequent mesenchymal tumor of unknown
      etiology and variable clinical symptoms. It usually affects black, middle-aged
      women. The most frequent symptoms are right hypochondrium pain, abdominal
      discomfort and constitutional syndrome with progressive liver damage. Diagnosis
      is difficult and detailed pathological analysis is required. Controlled clinical
      studies are lacking and there are no factors that predict the clinical course or
      serve as a guide to the most effective treatment. We report 3 cases with distinct
      clinical course ranging from clinical stability to dissemination and death.
      Treatment differed in the three patients.

PMID- 15989813
TI  - [Intestinal occlusion due to pancreatitis mimicking stenosing neoplasm of the
      splenic angle of the colon].
AB  - Colonic involvement in patients with severe acute pancreatitis or chronic
      pancreatitis is common and complications such as paralytic ileus, segmental
      necrosis and pancreatic-colonic fistulae have been described. However, mechanical
      occlusion of the colon due to pancreatitis is infrequent. We present the case of
      a 45-year-old man with occlusion of the colon secondary to asymptomatic
      pancreatitis mimicking a locally advanced stenosing neoplasm of the splenic
      angle. Ten years prior to the present episode the patient had presented acute
      alcoholic pancreatitis complicated by a pseudocyst requiring surgery. The current
      reason for admission was abdominal colic pain and constipation with onset 5 days
      previously. Contrast enema was administered showing colonic occlusion caused by
      stenosis at the splenic flexure, suggesting the presence of a neoplasm. Urgent
      laparotomy showed the presence of a tumor originating in the colon that
      infiltrated the splenic hilum. Subtotal colectomy and en-bloc splenectomy were
      performed. Histopathological analysis showed pericolonic inflammation and
      fibrosis secondary to pancreatitis; the colonic mucosa showed no tumoral
      infiltration. To date, fewer than 30 cases of this infrequent complication have
      been published.

PMID- 15989814
TI  - [Portal-splenic-mesenteric venous thrombosis secondary to a mutation of the
      prothrombin gene].
AB  - Thrombosis of the portal-mesenteric axis is an infrequent cause of intestinal
      ischemia or infarction. In addition to the multiple acquired factors that
      contribute to the development of this entity, hereditary risk factors, especially
      the factor V Leiden mutation and the G20210A mutation of the prothrombin gene,
      have been implicated. The G20210A mutation of the prothrombin gene is found in up
      to 40% of patients with splenic-portal-mesenteric thrombosis. The present case
      illustrates the unusual and nonspecific presentation of this mutation in the form
      of diarrhea and images of thrombosis of the superior mesenteric-portal vein and
      cavernous transformation of the portal vein. Delayed diagnosis is highly frequent
      since the clinical signs, laboratory investigations and radiological tests do not
      suggest the diagnosis. The patient received anticoagulant treatment and showed
      clinical improvement with complete portal-mesenteric recanalization. Currently
      the diagnostic technique of choice is magnetic resonance angiography or
      computerized tomography angiography and treatment consists of indefinite
      anticoagulation. This case illustrates that an unusual or atypical localization
      of venous thrombosis may be a manifestation of thrombophilia, emphasizing the
      importance of genetic screening in these cases.

PMID- 15989815
TI  - [Recombinant factor VII in the treatment of acute hemorrhage due to esophageal
      varices].

PMID- 15989816
TI  - [Screening the at-risk population for squamous cell carcinoma of the esophagus].
AB  - Together with adenocarcinoma, epidermoid esophageal carcinoma is the most
      clinically important neoplasm of the esophagus. Because of the low incidence of
      epidermoid esophageal carcinoma in the general population, strategies for its
      early diagnosis are not a priority compared with other neoplasms. However,
      because survival is low when the disease is diagnosed in symptomatic patients
      (less than 20% at 5 years), methods for its early diagnosis should be
      investigated. The use of cytology or Lugol chromoendoscopy in countries with a
      high incidence of epidermoid carcinoma or in individuals at increased risk
      (mainly alcoholics and smokers) has allowed early diagnosis and potentially
      curative treatment, substantially increasing life expectancy in this group of
      patients. These results should stimulate the evaluation and eventual
      implementation of programs to achieve early diagnosis and therefore greater
      survival in patients with epidermoid esophageal carcinoma in Western countries.

PMID- 15989817
TI  - [Endoscopic treatment of bleeding ulcers: has everything been said and done?].
AB  - Endoscopic treatment reduces bleeding recurrence, the need for surgery and
      mortality in patients with bleeding ulcers. However endoscopic treatment fails in
      10-15% of patients, leading to high morbidity and mortality. The therapeutic
      measures with demonstrated effectiveness in reducing the risk of hemorrhagic
      recurrence and its complications are combined endoscopic treatment (adrenaline
      plus a second hemostatic intervention) and proton pump inhibitors. Also useful,
      although there is less evidence, are immediate resuscitation and <<second look>>
      endoscopy. Some studies suggest that activated recombinant factor VII infusion or
      supra-selective arterial embolization can be useful in severe hemorrhage. Further
      studies are required to determine optimal treatment according to the
      characteristics of each patient.

PMID- 15989818
TI  - [Genetic and molecular biology techniques for the analysis of hereditary
      colorectal cancer].
AB  - The knowledge acquired in genetics and molecular biology over the last 2 decades
      has led to advances in the molecular diagnosis of some diseases, among them
      hereditary forms of colorectal cancer such as hereditary non-polyposis colorectal
      cancer and familial adenomatous polyposis. Moreover, the discovery of the genes
      causing these diseases has had implications beyond hereditary diseases since the
      same genes that cause hereditary forms of cancer also play a role in the much
      more frequent sporadic forms. Genetic diagnosis allows clinical diagnosis to be
      confirmed, as well as presymptomatic and even prenatal diagnoses to be made, with
      implications for patients with these hereditary diseases and their families.

PMID- 15989819
TI  - [Severe acute hepatitis after anesthesia with sevoflurane].

PMID- 15989820
TI  - [Celiac disease and selective IgA deficit].

PMID- 15989821
TI  - [Perforation of the small intestine due to cholesterol embolism].

PMID- 15989822
TI  - [Difficulties of selecting patients to receive treatment against hepatitis C
      virus in patients with HIV coinfection].

PMID- 15989824
TI  - [25 semFYC Congresses: a long distance covered, a long way to go].

PMID- 15989823
TI  - [Non-alcoholic fatty liver disease, serum iron indexes and iron concentration in
      the liver].

PMID- 15989825
TI  - [Medication for ending tobacco dependency. Current state].

PMID- 15989826
TI  - [Influence of maternal anxiety on the frequency of paediatric primary care
      visits].
AB  - AIM: To know the influence of mother's anxiety in the number of office visits
      made by the children al primary care paediatric setting. DESIGN: Case control
      study. SETTING: Primary care. 17th Health Area. Valencian Community. Spain.
      PATIENTS: 134 mothers. Overuse was defined as number of visits higher than the
      average of visits in all children plus one standard deviation in a certain
      period. 14.89% were over users. 46 mothers (35.12%) from over user children and
      85 (64.88%) from non over users. MEASURES: Anxiety scale STAI (Spielberger State
      Trait Anxiety Inventory) short form. Mother's job and number of mother's
      children. RESULTS: Mother's of over user's children score higher in STAI scale.
      Number of children or mother's job is not associated with STAI scores. In
      multivariate analysis anxiety is an important factor associated to over user's
      children. CONCLUSIONS: Mother's anxiety is associated with over user's children
      in primary care paediatric setting. This is a modifiable factor to influence in
      the number of inappropriate office visits.

PMID- 15989827
TI  - [Commentary: giving solutions and teaching people how to find solutions.
      Goodness, what a lot of work!].

PMID- 15989828
TI  - [Attitudes of primary care professionals in Madrid in relation to work with
      groups].
AB  - OBJECTIVES: To learn about attitudes of health professionals with regard to work
      with groups in primary care. DESIGN: Qualitative-structural research. LOCATION:
      Autonomous Community of Madrid. PARTICIPANTS: General practicioners,
      pediatricians, specialists in family and community medicine, nurses, and social
      workers. METHODS: 4 discussion groups and 4 open interviews. RESULTS: 3 positions
      were identified in these professionals: the "convinced," mainly social workers,
      followed by nurses and some doctors (more often the family/community specialists
      than the GPs), who "believe" in groups; the "sceptics," mostly doctors and some
      nurses, who defend a basically clinical-care model; and the "convincibles,"
      clearly the largest group, made up of doctors and nurses who, given a series of
      favourable conditions, would be prepared to make groups. CONCLUSIONS: The
      development of health education groups in primary care in Madrid is conditioned
      by the scepticism of professionals.

PMID- 15989829
TI  - [Usefulness of relaxation techniques for patients with ischaemic cardiopathy:
      intervention in a health district].
AB  - OBJECTIVE: To determine the effectiveness of a programme of relaxation used in
      primary care for patients with ischaemic cardiopathy (IC) through evaluation of
      the anxiety levels and the quality of life of these patients. DESIGN: Controlled
      intervention study without randomisation. SETTING: Two primary care teams in the
      city of Sabadell. PARTICIPANTS: Patients from 15 to 69 years old with IC:
      intervention group (IG), 57 patients; control group (CG), 47. Interventions. In
      the IG, conventional treatment and relaxation techniques (RT). In the CG,
      conventional treatment. MAIN MEASUREMENTS: Degree of anxiety was measured by
      means of the STAI scale-questionnaire. Quality of life was measured by means of
      the SF-36 health questionnaire. Blood pressure and smoking were recorded.
      RESULTS: At 12 months, 70% of patients practised relaxation at least for a short
      time. In the IG, anxiety dropped significantly at 3, 6, and 12 months, especially
      the anxiety characteristics scale, which was still significant at 12 months
      (P=.002). Quality of life at 3 and 6 months in the IG showed better scores in
      most dimensions except body pain. At 12 months, scores continued to be better
      than at the start (social function P=.012), except in the mental health
      dimension. No significant changes were found in blood pressure or tobacco
      consumption. CONCLUSIONS: Our results suggest that an RT workshop in primary care
      is beneficial if correctly applied and leads to improved quality of life.

PMID- 15989830
TI  - [Mental health perceived demand and training necessities of primary care
      physicians].
AB  - OBJECTIVE: To know the opinion of the primary health care (PHC) physicians on the
      assistance demand in mental health (MH), their training necessities and their
      attitudes about this disorders. DESIGN: Observational and transversal study.
      SETTING: Primary care. PARTICIPANTS: The subjects of the study were PHC
      physicians. From a total of 1191 PHC physicians in Castilla-La Mancha region, 301
      were selected by random stratified sampling. Main measurements. A self
      complimented questionnaire was elaborated, being identified the following
      variables: professional and sociodemographics characteristics, their perceived
      demands of MH problems, perceived difficulties in resolution, training in MH,
      knowledge about specialized resources and their attitudes about mental disorders.
      RESULTS: 63.5% (95% confidence interval [CI], 57.6-69.4) considered that the
      mental problems are related with, at least, 20% of the consultations. Very
      frequent consulted problems were: anxiety disorders (75.9%), affective disorders
      (73.5%), and somatoform disorders (40.5%). 63.6% (95% CI; 57.8-69.6) considered
      to have enough information about specialized resources. About attitudes, 43.7%
      (95% CI; 37.7-49.8) said the PHC physicians cannot be taken charge of the
      existent demand. This opinion as significantly more frequents in physicians with
      more patient assigned, more assistance pressure, without postgraduate assistance
      formation (Spanish MIR system), with less perceived demand, without training in
      MH and worse knowledge of the specialized resources. CONCLUSIONS: In opinion of
      most of the physicians the mental disorders are related with, at least, 1 of each
      5 consultations. A high proportion considers that the teams of PHC cannot be
      taken charge of the existent demand, mainly when it is high the assistance
      pressure. Most says that more specific training should exist in MH and more
      coordination with the specialized services.

PMID- 15989831
TI  - [Prescription medicines information: Spanish general population survey].
AB  - OBJECTIVE: To assess Spanish general population opinion on prescription medicine
      information which they currently access or would like to. Design. Cross-sectional
      descriptive study through telephone interviews. Setting. Spanish general
      population. February-March 2003. PARTICIPANTS: A total of 1069 subjects from 16
      to 90 years old were interviewed. Main measures. Questionnaire developed after
      reviewing legislation and literature, and validated by an expert panel in medical
      information. RESULTS: A total of 87.7% of subjects usually obtain medicines upon
      medical prescription. The most important prescription medicine information
      sources are drug information leaflet (75.9%; 95% CI, 73.3-78.5), physicians
      (54.9%; 95% CI, 51.8-58.0), pharmacists (17.4%; 95% CI, 15.1-19.7 and nurses
      (6.7%; 95% CI, 5.2-8.2). Less than 3% of subjects obtain prescription medicine
      information through Internet. A total of 52.9% (95% CI, 49.9-55.8) of subjects
      feel they are inadequately informed about prescription medicine and would like to
      have more access to it through sources different than health care staff. A total
      of 45.6% (95% CI, 42.6-48.6) of subjects would find convenient to receive
      information from pharmaceutical companies. This information should be qualified
      and supervised by health authorities. Brief written materials provided by
      physicians or pharmacists, would be the most appropriate way for patients to
      obtain prescription medicine information from pharmaceutical companies.
      CONCLUSIONS: Spanish general population feel they have poor information on
      prescription medicine and would like to get access to qualified information from
      different sources, including the one provided by the pharmaceutical industry.

PMID- 15989832
TI  - [Ethical approaches to treating tobacco dependency].

PMID- 15989833
TI  - [Moderate alcohol consumption and mortality for various reasons].

PMID- 15989834
TI  - [Study of the professional quality of life of primary care workers in Madrid area
      1].

PMID- 15989835
TI  - [Toxic hepatitis after flutamide treatment].

PMID- 15989836
TI  - [Improvised sexual education to fill in the gaps: does it prevent sexually
      transmitted diseases?].

PMID- 15989837
TI  - [Authorization for use of photographic images in the educational model of primary
      care].

PMID- 15989838
TI  - [Assessment of long-term renal function after nephrectomy. Study of 53 patients].
AB  - BACKGROUND AND OBJECTIVE: Patients with unilateral nephrectomy maintain the
      remaining kidney function over time, as it has been described in healthy kidney
      donors. PATIENTS AND METHOD: We performed a cross-sectional study of 53 patients
      who were followed 5 or more years after nephrectomy. Serum creatinine, BUN,
      Glomerular Filtration Rate (GFR) (24 hours urine collection and Cockcroft
      formula), microalbuminuria, proteinuria, Body Mass Index and the annual loss rate
      of renal function were measured or calculated over the follow-up period. We
      retrospectively considered the presence of risk factors like diabetes,
      hypertension, microalbuminuria, dyslipemia, smoking habit, obesity and ACE
      inhibitors or angiotensin-receptor antagonists treatment. We divided our patients
      into two groups: group I (normal or mild renal failure: GFR > 50 cc/min and or
      serum creatinine < 1.4 mg/dL) and group II (moderate or severe renal failure).
      RESULTS: The main cause of nephrectomy was renal tuberculosis, followed by
      lithiasis and pyonephrosis. In addition, 7.5% of patients were kidney donors. At
      the time of study, 22.7% had diabetes, 60.4% hypertension and 39.6% were obese.
      The mean age was 60 years (37 years at the moment of nephrectomy). The GFR final
      mean was 53.6 cc/min (58.8 cc/min by Cockcroft formula). The mean renal function
      loss rate was 1 cc/min/year. 35% of the patients had moderate or severe kidney
      failure and were included in group II; 32% had proteinuria and 56.6% had abnormal
      microalbuminuria. The univariate risk factors analysis for the development of
      renal failure showed inter-group statistical significative differences in current
      age, nephrectomy age, microalbuminuria, proteinuria, and hypertension prevalence
      (p = 0.008). With regard to the progression rate, we found a significant
      correlation with final microalbuminuria (r = 0.358, p = 0.03). Current age and
      final proteinuria were found to be significant risk factors in the multivariate
      analysis. CONCLUSIONS: A high prevalence of renal insufficiency was found among
      patients with unilateral nephrectomy, which is mainly related to age and
      proteinuria. The renal function loss rate is slow and is influenced by
      microalbuminuria.

PMID- 15989839
TI  - [Linguistic adaptation into Spanish and validation of the Arthritis Treatment
      Satisfaction Questionnaire].
AB  - BACKGROUND AND OBJECTIVE: Linguistic adaptation and validation into Spanish of
      the ARTS questionnaire, a self reported instrument designed to measure four
      osteoarthritis treatment satisfaction dimensions: treatment advantages, treatment
      convenience, apprehension about treatment and satisfaction with medical care.
      MATERIAL AND METHOD: Adaptation was performed using conceptual equivalence,
      supervised by a panel of 6 experts and 4 independent translators, who were in
      charge of performing translation and back-translation of the items. A sample of
      patients suffering from knee, hip or column osteoarthritis was used to estimate
      the psychometric properties of feasibility, reliability, validity and sensitivity
      to change. Three groups were identified: adequate analgesic effect and
      tolerability, treatment-switch because of a weak analgesic effect, and treatment-
      switch due to poor tolerability. The ARTS was administered at baseline, 1 week
      later for retest, and after 4 weeks of treatment with NSAIDs or Cox II
      inhibitors. RESULTS: A sample of 163 patients was formed (67.7 [9.2] years old).
      No floor or ceiling effects were found, items were well understood and non-
      response rates were below 1%. Cronbach's alpha for the total scales was 0.85, and
      the intraclass correlation coefficient was 0.81. Exploratory factor analysis
      yielded 4 dimensions which were coherent with those proposed by the original
      authors. Concurrent validity was measured with SF-36, a pain VAS instrument, a
      treatment compliance VAS, and the Morisky-Green compliance questionnaire. The
      adapted instrument showed a good discriminatory validity, and it was able to
      distinguish between patients needing a change in treatment and those who did not
      need it. It was also sensitive to changes in patients' treatment effectiveness
      after a 30 days follow up. CONCLUSIONS: A psychometrically valid and conceptually
      equivalent ARTS questionnaire has been produced to explore satisfaction with
      treatment in patients with osteoarthritis in Spanish speaking countries.

PMID- 15989840
TI  - [Electrocardiographic and echocardiographic findings in children with overweight
      and obesity].
AB  - BACKGROUND AND OBJECTIVE: Obesity is associated with cardiovascular risk factors
      and heart failure. SUBJECTS AND METHOD: Thirty children with overweight or
      obesity were matched with 30 healthy children. Corrected QT interval (QTc) and QT
      dispersion (QTd), left ventricular mass, left ventricular mass index, fractional
      shortening and fractional ejection, were measured. RESULTS: QTc and QTd were
      significantly greater in patients with overweight or obesity than in the control
      group. Left ventricular mass and left ventricular mass index were significantly
      higher in overweight or obese children than in controls. CONCLUSIONS: Children
      with overweight-obesity have an increase of corrected QT and QT interval
      dispersion and of the volume and mass of the left ventricle and a greater risk of
      arrhythmia, in relation to controls. These results make consider the need for a
      special cardiac monitoring of obese children, especially in the severe forms.

PMID- 15989841
TI  - [Varicella outbreak in a work center for psychologically handicapped adults].
AB  - BACKGROUND AND OBJECTIVE: An outbreak of varicella is described in a training and
      work center for psychologically handicapped adults with a high susceptibility to
      the disease. PATIENTS AND METHOD: Descriptive and case-control study. A
      questionnaire self-complimented by parents and staff of the center was used. A
      serologic study in order to determine antibodies againts varicella was carried
      out for people without varicella vaccination or disease history. RESULTS: Four
      cases of varicella occurred among 56 students of the center and none among the
      staff (12 people). 51.8% of students had not history of varicella versus 8.3% of
      staff (p = 0.009). A recommendation of vaccination against varicella was made for
      people without history of varicella, and 52.2% were vaccinated. After
      vaccination, no new cases occurred. In the serological study (11 students and 1
      staff), 5 students were sero-negative. In the case-control study, risk of
      suffering varicella was lower for students with history of varicella, those
      vaccinated against varicella and those attending less commonly the center.
      CONCLUSIONS: The outbreak occurred in a high susceptible population, and it is
      suggested that it is a previously unidentified group of risk. Serological studies
      of varicella with vaccination of susceptible individuals in these populations may
      be indicated.

PMID- 15989842
TI  - [Satisfaction with treatment].

PMID- 15989843
TI  - ["Seronegative" myasthenia gravis and antiMuSK positive antibodies: description
      of Spanish series].
AB  - BACKGROUND AND OBJECTIVE: Recently, the presence of antibodies to a muscle
      specific tyrosine kinase (MuSK) has been reported in some patients with
      seronegative generalized myasthenia gravis. Our objective was to describe a group
      of patients who were positive for anti-MuSK antibodies. PATIENTS AND METHOD:
      Detection of antibodies using a radioimmunoassay was performed in the serum of 26
      patients with generalized myasthenia gravis. We identified 9 patients with anti
      MuSK antibodies (MuSK+). Clinical and therapeutic data from these patients were
      reviewed. RESULTS: Eight of nine patients were women aged between 20 and 40
      years. Clinically, all of them showed prevalent bulbar signs, initially or during
      the progression of the disease. 77% of patients showed ocular involvement and 44%
      had symptoms of fatigability involving limbs. None of them improved upon
      thymectomy. Response to acetylcholinesterase inhibitors was variable. All of them
      responded to immunotherapy, although 30% required polytherapy. CONCLUSIONS: The
      study of anti-MuSK antibodies defines a subgroup of patients, 34,61% in our
      series, with seronegative generalized myasthenia. This group is characterized by
      an homogenous clinical presentation with prevalent bulbar symptoms. The knowledge
      of the immunopathogenic mechanisms of anti-MuSK antibodies will allow a better
      understanding of both the variable response to acetylcholinesterase inhibitors
      and the absence of response to thymectomy in these patients.

PMID- 15989844
TI  - [Female doctors: from incorporation to discrimination].

PMID- 15989846
TI  - [Torsades de pointes in an HIV infected patient].

PMID- 15989845
TI  - [Medical management of primary nonalcoholic fatty liver disease].
AB  - The need for an effective and safe medical treatment of nonalcoholic fatty liver
      disease is urgent due to its high prevalence and progressive character. At the
      moment, therapeutic strategies are largely empirical and based on the control of
      associated clinical conditions (especially obesity, type 2 diabetes mellitus, and
      hypertriglyceridemia) and the use of some specific drugs (insulin sensitizing
      agents, cytoprotectives, antioxidants, and anticytokines) as an attempt to
      counteract known elements of the pathogenesis. None of these specifics measures
      have been found to display enough evidence to recommend their clinical use. It is
      indispensable to join efforts in coordinated networks to define, as soon as
      possible, the best treatment and the best time to start it.

PMID- 15989847
TI  - [Brain abscess caused by Eikenella corrodens and Streptococcus intermedius
      associated with bowel carcinoid tumour].

PMID- 15989848
TI  - [Sporadic hepatitis E in Spain: study of 9 autochthonous and 3 imported cases].

PMID- 15989849
TI  - [Acute renal failure associated to hepatitis A infection].

PMID- 15989851
TI  - [Impact of age and comorbidity on survival and toxicity of irradiated prostate
      cancer patients].
AB  - BACKGROUND AND OBJECTIVE: We intended to assess the impact of age on radiation
      outcome in patients treated for prostate cancer with 2D planning radiation
      therapy in clinical practice at the Hospital Clinic of Barcelona Radiation
      Oncology Department. PATIENTS AND METHOD: One hundred eighty three patients,
      treated from November 1993 to April 1999, were included. Median follow-up was
      41.8 months and median age was 70 years old. Median dose to prostate was 70 Gy.
      Univariate (Kaplan-Meier with log rank test comparison) and multivariate analysis
      (Cox's regression models) were done to assess the effect of age on toxicity and
      to study prognostic factors for disease control, survival and radiation treatment
      toxicity. RESULTS: Five years disease free survival probability was 61.94%, with
      an overall survival probability of 82.83%. Although comorbidity increased
      significantly with age, reduced overall survival by a factor of 0.4, from 94.85%
      to 78.55% at 5 years. No differences were seen with regard to age in acute or
      late toxicity. Five years toxicity free probability was 66.46%. CONCLUSIONS:
      Comorbidities decrease life expectancy in prostate cancer patients treated with
      radiation. Age does not necessarily suppose an increased risk of late toxicity
      for selected patients.

PMID- 15989852
TI  - [Contribution of human papillomavirus second-generation hybrid capture test for
      the diagnosis of cervical pathology in HIV-infected outpatients].
AB  - BACKGROUND AND OBJECTIVE: The causal relationship between human papillomavirus
      (HPV) and cervical cancer is well established. The initial diagnosis of HPV
      related cervical infection is currently performed by HPV-associated changes in
      cervical cytology. We aimed to study the accuracy and concordance between HPV ADN
      detection by second-generation hybrid capture (HC-2) and cervical cytological
      changes for the diagnosis of HPV cervical infection in human immunodeficiency
      virus (HIV+) outpatients. PATIENTS AND METHOD: From March 1999 to August 2002,
      139 HIV+ patients were included. HPV infection was determined by cytology and HC
      2. The accuracy and level of concordance between both techniques was analyzed.
      RESULTS: The applicability of the HC-2 test was 96%. Sixty-eight (49%) patients
      were diagnosed with HPV infection by HC-2. High-oncogenetic-risk HPV genotypes
      were detected in 64 (46%) patients. The sensitivity, specificity and positive and
      negative predictive values of HC-2 in HPV detection were 78%, 69%, 61% and 83%,
      respectively. The concordance was K = 0.44 (95% confidence interval, 0.29-0.60);
      p < 0.001. CONCLUSIONS: The HC-2 diagnostic technique for HPV-related cervical
      infection in HIV+ patients is a sensitive and specific test. The combined use of
      both tests might increase the diagnostic efficacy, and hence have positive
      repercussions on cervical pathology screening on an outpatient basis.

PMID- 15989853
TI  - [Effect of the incorporation of a general practitioner on emergency department
      effectiveness].
AB  - BACKGROUND AND OBJECTIVES: To know the effect that the presence of a general
      practitioner (GP) has on emergency department's effectiveness, efficiency and
      health care. PATIENTS AND METHOD: Prospective interventional study carried out in
      the emergency medicine unit fast track area (FTA), which is ideally opened from 8
      am to 12 am, and staffed by 2 residents. INTERVENTION: 8 resident hours (from 4
      pm to 12 am) were substituted by 8 GP hours. The study period was August 2002 (GP
      presence), and the control period, October 2002. From each period, 10 days and
      100 patients were randomly selected. From each day, FTA census (P), percentage of
      revisits and patients leaving without being seen, elapsed time to FTA actual
      closing (OT), percentage of patients moved to the observation area, and
      percentage of admissions were recorded. From each patient, epidemiological and
      clinical characteristics, waiting time to be seen (WT), number of tests
      performed, elapsed time to treatment (TT), and length of stay (LOS) were
      collected along with the number of patients finally discharged without hospital
      specialist consultation and those discharged with no test ordered. To assess
      perceived care quality, a telephone survey was performed. Three effectiveness
      indexes were defined and determined: P/WT (E1), P/OT (E2), and perceived care
      quality/perceived WT (E3). Finally, fixed and variables costs (C) from both
      periods were calculated, and cost-effectiveness analysis for each effectiveness
      index and period performed. RESULTS: Periods showed no differences regarding
      daily census and patient characteristics. In the study period (GP presence), all
      time variables significantly improved: 20% reduction in WT, 25% in TT, 36% in
      LOS, and 17.5% in OT. A decrease in the number of tests ordered (41% less), in
      the percentage of patients moved to the observation area (78% less), and in the
      revisit rate (75% less) was also noted. Finally, E1 improved in 77% and E2 in
      51%. Cost-effectiveness analysis clearly supported the study period, showing a
      decrease in C/E1 (55% less), in C/E2 (33% less), and in C/E3 (6% less). From the
      telephone survey, no differences between periods were detected except a perceived
      WT in the study period lower than that in the control period. CONCLUSIONS: The
      presence of a GP in a FTA leads to an improvement in the effectiveness and
      quality of care received by attended patients. In addition of these important
      features, this presence is also efficient. Therefore, it is an intervention that
      could be taken into account by administrators to better manage emergency
      departments.

PMID- 15989854
TI  - [Usefulness of adding antibiotic to cement in one stage exchange of chronic
      infection in total hip arthroplasty].
AB  - BACKGROUNDS AND OBJECTIVE: Direct exchange using antibiotic-impregnated cement is
      a treatment option for hip prosthesis infection (HPI). Nevertheless, a local
      antibiotic use is not always possible. We present our experience with direct
      exchange with and without antibiotic-impregnated cement. PATIENTS AND METHOD:
      Fourteen patients with a HPI were treated with direct exchange. The femoral
      component was cemented with an antibiotic in 7 cases and in 7 it was not
      cemented. The patients received antibiotic prophylaxis and antibiotic treatment
      for a mean of 3 months. Clinical evolution of the infection was prospectively
      assessed. RESULTS: There were no differences with regard to the clinical and
      microbiologic characteristics between both groups. In the last control (minimum 2
      years) all the patients were cured. CONCLUSIONS: Our results suggest that direct
      exchange without local antibiotic is an option in HPI. Further studies are needed
      to evaluate the usefulness of antibiotic loaded cement.

PMID- 15989855
TI  - [Treatment with curative intention of prostate cancer depending on age and life
      expectancy].

PMID- 15989856
TI  - [Antidepressant drugs in children and adolescents].

PMID- 15989857
TI  - [Eosinophilic fasciitis: analysis of a series of 10 patients].
AB  - BACKGROUND AND OBJECTIVE: Eosinophilic fasciitis is an uncommon scleroderma-like
      syndrome with unknown etiology and pathogenesis. We report the clinical
      manifestations and response to therapy in a series of patients diagnosed with
      eosinophilic fasciitis. PATIENTS AND METHOD: The records of 10 eosinophilic
      fasciitis patients seen at our hospital between 1996-2004 were reviewed. RESULTS:
      Five patients were males, ages ranged from 20 years to 67 years, with a mean of
      59 years. Patients were followed for 33.4 (27.1) months (SD). Nailfold
      capillaroscopy was near normal in all patients. Only one patient had antinuclear
      antibody positivity, and another had an autoimmune thyroiditis. No significant
      relationship was detected between the eosinophil count and the extent of skin
      induration. The clinical course was inadequate and the treatment response poor in
      patients with spreading cutaneous induration (p = 0.008). These patients had more
      often ventilatory restriction and perimyositis. CONCLUSIONS: Eosinophilic
      fasciitis does not always have a good prognosis. Ventilatory restriction,
      perimyositis and poor treatment response are not infrequent in a series of
      patients attended in a general hospital.

PMID- 15989858
TI  - [Hepatic lesions and shock in a 75-year-old patient with chronic myeloid
      leukemia].

PMID- 15989859
TI  - [Health education of patients in primary care].

PMID- 15989860
TI  - [Hiccups crisis following paramethasone intraarticular injection].

PMID- 15989861
TI  - [What should Lalonde think on the decision taking in health care?].

PMID- 15989862
TI  - [Treatment of severe refractory psoriasis with infliximab. Clinical outcomes
      after one year of therapy].

PMID- 15989864
TI  - [Non-reassuring fetal status, perinatal asphyxia and neonatal encephalopathy].

PMID- 15989865
TI  - [Effect of hygiene interventions on the thermal stability of extremely low-birth
      weight newborns in the first two weeks of life].
AB  - INTRODUCTION: A prospective study was performed of a cohort of extremely low
      birth-weight (ELBW) premature neonates (birth weight 500 to 1,000 g)
      consecutively admitted to the neonatal intensive care unit. The aim of this study
      was to examine the thermal changes that occur during all the hygiene-related
      interventions in ELBW infants in the first 2 weeks of life. PATIENTS AND METHODS:
      The study was carried out for 10 consecutive months in the Neonatology Service of
      La Paz University Hospital. We studied all consecutively admitted ELBW infants
      who satisfied the following criteria: a) adequate weight for gestational age; b)
      survival for at least 1 week, and c) no major congenital malformations or
      dysmorphic features. The infants included in the study were managed according to
      a standard care protocol for maintaining thermal stability and preventing cold
      induced stress. Central temperature (Tc) was measured in the axilla and
      peripheral temperature (Tp) was measured on the sole of the foot. Both
      temperatures were continuously monitored for a) a period of scheduled non
      handling--baseline period--and b) during and after a series of "hygiene
      interventions". In each of these periods, Tc and Tp were continuously monitored
      and recorded at 10 min intervals for the first 30 minutes and then at 30 min
      intervals until completing a 180 min period. RESULTS: Although incubator
      temperature was raised by a mean of 3 degrees C during hygiene interventions,
      hygiene was accompanied by a change in body temperature that remained fairly
      constant throughout the study period; Tc and Tp decreased by a mean of 1 degrees
      C with respect to baseline temperature. A fall in axillary temperature to less
      than 36.5 degrees C was observed in 87.4 % of recordings and a fall to less than
      36 degrees C was observed in 45.5 %; axillary temperature remained below 36.5
      degrees C for a mean duration of almost 1 hour. The differential temperature (Td
      5 Tc - Tp), an indicator of thermal stress, was more than 1 degrees C for a mean
      duration of more than 80 min and > 2 degrees C for more than 20 minutes in both
      the first and second weeks of life. CONCLUSIONS: During hygiene interventions,
      ELBW infants experienced a sharp fall in central and peripheral body temperature.
      After hygiene interventions, these neonates had a Td suggestive of prolonged
      thermal stress, despite the use of standardized care protocols designed to avoid
      or minimize the potential effects of hygiene interventions on neonatal
      temperature.

PMID- 15989866
TI  - [Early or late umbilical cord clamping? A systematic review of the literature].
AB  - INTRODUCTION: There is wide variability in clinical practice in the moment of
      clamping the umbilical cord. Opinions in the medical community differ on the harm
      and/or benefits, both for the mother and for the newborn, of early versus late
      cord clamping. Currently, the debate among those who defend and/or criticize one
      or other of these practices continues. The aim of this study was to evaluate the
      effects of early versus late clamping of the umbilical cord in full-term newborns
      on maternal and neonatal outcomes. MATERIAL AND METHODS: A literature search of
      randomized clinical trials was carried out in the Cochrane Library, MEDLINE and
      Lilacs. It was completed with a hand search of references in relevant articles.
      All randomized controlled clinical trials of good methodological quality that
      compared early versus late cord clamping in term newborns were selected. RESULTS:
      Of seven identified studies, four had the required characteristics for inclusion
      in this systematic review. Comparison of early versus late clamping in these
      studies revealed that late clamping could diminish the prevalence of children
      with low iron reserves at 3 months of age by 50%, but this result comes from a
      study that lost more than 40% of the patients during follow-up. The results
      concerning anemia at 3 months of age showed statistical heterogeneity since the
      two studies that analyzed this outcome had opposite results. For other outcomes
      such as birth weight, Apgar < 5, and tachypnea the studies were too small for
      significant differences to be detected. CONCLUSIONS: This review shows that there
      is no clear evidence for defending any of the modalities of cord clamping in full
      term newborns. Further research is needed to identify the best moment for cord
      clamping.

PMID- 15989867
TI  - [Influenza virus infections in infants aged less than two years old].
AB  - INTRODUCTION: Influenza is a major cause of respiratory tract illness in infants.
      The clinical characteristics of these infections are non-specific and the burden
      of influenza is frequently underestimated in very young children. The objective
      of this study was to describe confirmed influenza infections in infants < 2 years
      attended in a level II public hospital. A second-rate aim was to compare
      influenza infections in hospitalized infants with respiratory syncytial virus
      (VRS) infection in the same population. PATIENTS AND METHODS: We performed a
      descriptive, prospective study between 1991 and 2003 in infants younger than 24
      months of age, who were admitted to the Severo Ochoa Hospital (Leganes. Madrid)
      with fever or respiratory tract infection. Virological diagnosis was made with
      direct immunofluorescent assay and/or reverse transcription-polymerase chain
      reaction on specimens obtained from nasopharyngeal washings. The patients'
      clinical characteristics were recorded. Patients with influenza infection were
      compared with a similar group of infants with RSV infection. RESULTS: We analyzed
      hospitalized 100 infants with influenza infection. Influenza caused 4.1% of the
      admissions in infants with fever or respiratory tract infection. Influenza A was
      isolated in 83%, influenza B in 12% and influenza C in 5% of the patients. The
      mean age of hospitalized infants was 8.3 +/- 5.9 months and the most frequent
      clinical diagnoses were bronchiolitis in 38%, recurrent wheezing in 25%, upper
      respiratory tract infection in 19% and pneumonia in 9%. Fever > 38 degrees C was
      present in 83% of the patients. Radiologic infiltrate was found in 65% of the
      children. Oxygen saturation less then 95% was present in 44%. In children under 6
      months of age fever was less frequent (p = 0.049) and upper respiratory tract
      infection was more frequent (p = 0.01). Patients with influenza virus infection
      were older (p = 0.002), more frequently presented fever (p < 0.0001) and
      radiologic infiltrate (p < 0.001) than infants with RSV infection. Bronchiolitis
      was more frequent in the RSV group (p = 0.006). CONCLUSIONS: Influenza infection
      is a major cause of respiratory tract disease in hospitalized infants. It is an
      etiologic cause of bronchiolitis, recurrent wheezing, and fever and radiologic
      consolidations are frequent. Clinical presentation is milder in children under 6
      month of age. The characteristics of influenza infection differ substantially
      from those of RSV infection.

PMID- 15989868
TI  - [Skin and soft tissue infections caused by Haemophilus influenzae type b over a
      30 year period].
AB  - INTRODUCTION: The skin and soft tissue infections caused by Haemophilus
      influenzae type b (Hib) are usually mild but can be potentially serious due to
      the high probability of bacteremia. Prompt instauration of empiric intravenous
      antibiotic therapy according to the localization and characteristics of the
      lesion is mandatory to prevent severe complications. PATIENTS AND METHODS: Of 257
      children admitted to the Children's Hospital of La Fe due to invasive Haemophilus
      influenzae type b disease (1973 to 2003), we reviewed 15 cases (5.8%) of skin and
      soft tissue infections, their outcome, complications and sequelae. RESULTS: Ten
      children (66.7%) were aged < 2 years old. In eight patients (53.3%) there was a
      history of upper respiratory tract infection. Localization was in the head in 9
      children (60%) and blood culture was positive in 10 patients (66.7%). Meningitis
      was a complication in 2 children (13.3%) and limited mobility of the hand was a
      sequel in one child (6.6%). After the universal establishment of the Hib vaccine
      in 1997, 3 new patients were admitted; 2 children with an infected thyroglossal
      cyst and another with cellulitis in the left leg. Of these children, one had
      received only the three primary doses of the vaccine but not the booster dose,
      and the remaining two were unvaccinated immigrant children. CONCLUSION: Skin and
      soft tissue infections caused by Hib are potentially severe diseases with a risk
      of complications and sequelae. Due to the increase in unvaccinated immigrants and
      possible vaccine failures, universal immunization and epidemiological
      surveillance of carriers should be carried out to achieve total eradication.

PMID- 15989869
TI  - [Five-year follow up of lipid profile in children in the Rivas-Vaciamadrid
      study].
AB  - OBJECTIVE: To evaluate lipid balance in children after a 5-year follow-up and
      tracking between initial and final levels. METHODS: Two hundred eighty-one
      children included in the Rivas-Vaciamadrid study were evaluated at the ages of 6
      and 11 years. In all children, total cholesterol (TC), triglycerides (TG), high
      density lipoprotein-cholesterol (HDL-C), and apoproteins A1 (Apo A) and B100 (Apo
      B) were measured. Low-density lipoprotein-cholesterol (LDL-C) was determined and
      the Apo B/Apo A, TC/HDL-C, and LDL-C/HDL-C ratios and the atherogenic index were
      calculated. RESULTS: At 11 years of age, lipid balance was worse in girls than in
      boys. Levels of TG and HDL-C were significantly higher at the age of 11 years
      than those at the age of 6 years, but levels of the remaining variables analyzed
      were lower, except for Apo A and TC, which showed a non-significant increase. The
      correlation coefficients between values at the ages of 6 and 11 years were
      significant for all variables and the highest was LDL-C in girls (0.711). Kappa
      and Nishio tracking indexes were significant for all variables and were highest
      for the atherogenic index (0.431 and 6.71 respectively) and lowest for TG (0.129
      and 2.85 respectively). Subjects in the highest quartile at 6 years old had a
      relative risk of 8.04 (CI 4.34-14.88) for having the same atherogenic index at
      the age of 11 years and a relative risk of 1.91 (CI 1.05-3.46) for having the
      same TG value. CONCLUSION: There is a significant correlation between lipid
      profile values in children at the ages of 6 and 11 years. The best tracking was
      found in the atherogenic index.

PMID- 15989870
TI  - [Prevalence of obesity in 14-year-olds in four primary care centers. Trends in
      weight changes since the age of two years old].
AB  - INTRODUCTION: Childhood obesity is an increasingly common diagnosis in western
      society and is related to certain changes in lifestyle. Because of its
      persistence in adulthood and its relationship with several pathological entities
      such as cardiovascular disease and diabetes, it has become one of the most
      important problems in children's health. The objective of this study was to
      determine the prevalence of obesity and overweight in 14-year-old adolescents
      attending the pediatric outpatient clinics of a primary care center in 2003, and
      their weight changes from the age of two years old. SUBJECTS AND METHODS: A long
      term study of 277 children born in 1989 was performed. Their body mass index
      (BMI) was calculated at the age of 2,3,4,6,8,11 and 14 years. Obesity was defined
      as a BMI > P95 and overweight as a BMI > P85 according to the Centers for Disease
      Control and Prevention (CDC) growth charts 2000. RESULTS: The prevalence of
      obesity in 14 year-olds was 13.2% (15.2% in boys and 11.5% in girls). The
      prevalence of overweight was 17.4% (18.7% in boys and 16.2% in girls). Gender
      differences were not significant in any of the age groups studied. CONCLUSIONS:
      The prevalence of obesity and overweight in 14 year-old adolescents in our
      centers is considerable and is similar to that reported in other Spanish regions.
      The pediatric outpatient clinics of primary care centers should play an active
      role in the control and prevention of obesity.

PMID- 15989871
TI  - [New indications for the inactivated influenza vaccine in the pediatric
      population (2004-2005)].
AB  - Several epidemiological studies have indicated that, in all countries and in
      distinct epidemic years, the highest rates of influenza infection (between 15%
      and 42%) occur in the pediatric population, especially in school-aged children.
      Over various influenza seasons, the rates of annual outpatient visits
      attributable to influenza vary from 6-29% of children. Influenza and its
      complications have been reported to result in a 10-30% increase in the number of
      antibiotic courses prescribed to children during the influenza season. Current
      percentages of influenza vaccination in children are very low, although the
      hospitalization rates for infectious complications in children under 5 years are
      at least equal to those observed in individuals aged more than 65 years. The
      reasons for these low immunization rates are unknown, but many factors could be
      involved, especially the need for annual revaccination. In 2003 the Advisory
      Committee on Immunization Practices (ACIP) recommended influenza immunization
      only in children at high risk for influenza complications and in those living
      with someone in a high-risk group. However, they encouraged vaccination of all
      children aged 6-23 months old. After a review of various epidemiological studies,
      in 2004 both the ACIP and the American Academy of Pediatrics recommended
      systematic immunization of all healthy children within this age group. However,
      both institutions advise that before the routine introduction of influenza
      immunization in all children aged 6-23 months old, immunization programs in high
      risk children need to be implemented.

PMID- 15989872
TI  - [Risk factors for neuroblastoma].
AB  - INTRODUCTION: NB is the most frequent pediatric cancer arising in the sympathetic
      nervous system and represents a serious healthcare challenge because: 1) it is
      the most frequent neoplasm in the first decades of life; 2) it biological
      behavior is unpredictable (spontaneous regression, maturation to ganglioneuroma,
      and localized and metastasized variants); and 3) little is known about most of
      the risk factors involved in its etiopathogenesis. The objective of this study
      was to disseminate knowledge of constitutional and environmental (physical,
      chemical, biological and social) risk factors linked to the development of
      neuroblastoma (NB), with various levels of scientific evidence. To seek
      collaboration among pediatricians in the research project "Environment and
      Pediatric Cancer". MATERIAL AND METHODS: We performed a systematic review of the
      literature published in the previous 25 years on risk factors for NB diagnosed in
      the first two decades of life, using Medline, the Science Citation Index and
      Embase. Search profiles were: "neuroblastoma/childhood sympathetic nervous system
      neoplasms and risk factors/etiology/epidemiology". The most interesting articles
      and the most relevant references contained therein were selected. RESULTS: With
      greater or lesser scientific evidence, the following risk factors increase the
      risk of developing NB: genetic factors; geographic factors; ethnic factors;
      socioeconomic factors; infectious factors; physical factors; parental
      occupational exposure; gestational factors; and perinatal and maternal factors.
      Preventive factors associated with a lower risk of developing NB are
      breastfeeding and intake of vitamin supplements during pregnancy. CONCLUSIONS:
      The main barriers to the identification of evidence-based risk factors involved
      in the development of NB are its complex biology and clinical course, its
      relative rarity and the difficulty of performing epidemiological studies.
      Research on constitutional and environmental factors involved in its
      etiopathogenesis should be stimulated. The best preventive strategy is to
      recommend breastfeeding for more than 6 months.

PMID- 15989873
TI  - [Outcome of two patients with Hurler's syndrome under enzyme replacement therapy
      with human recombinant alpha-L-iduronidase].
AB  - We performed a prospective study of two patients with Hurler's syndrome (aged 4.8
      years and 17 months at the beginning of the intervention) under enzyme
      replacement therapy with human recombinant alpha-L-iduronidase for 452 and 28
      weeks respectively. The aim of this study was to analyze the safety and efficacy
      of the intervention during the treatment periods. Several diagnostic imaging
      tests, clinical examinations, and serial laboratory determinations were performed
      to demonstrate the effectiveness of the therapy in both patients. In patient 1 (a
      boy aged 4.8 years, homozygote W402X), the treatment was always intended to be
      palliative because of the advanced stage of the disease. In patient 2 (a 17-month
      old girl, heterozygote W402X) the treatment was initiated early with subsequent
      clinical stabilization without acquisition of regressive factors. Bone marrow
      transplantation from an unrelated donor was successful. Currently, because of the
      lack of histocompatible bone marrow donors, transplantation of hematopoietic stem
      cells from umbilical cord blood or peripheral blood are being performed with
      satisfactory results. In the future, gene therapy may be able to prevent the
      diseases associated with Hurler's syndrome and halt the neurocognitive
      deterioration characteristic of these patients.

PMID- 15989874
TI  - [Castleman disease].
AB  - Castleman disease or angiofollicular hyperplasia is a rare disorder included in
      the group of lymphoproliferative disorders. This entity was originally described
      by Castleman in 1956. The etiology remains unknown but it is postulated to be a
      reactive lymphoid hyperplasia due to chronic antigenic stimulation caused by a
      viral infection. The disease presents in young adults and is more frequent in
      women; it is exceptionally rare in the pediatric age group. It is classified into
      two clinical groups (localized disease and disseminated disease) and there are
      two histologic variants (hyaline-vascular and plasma cell Castleman disease).
      Localized disease is usually asymptomatic, has a good prognosis, and is the most
      common presentation in pediatric patients, usually corresponding to highly
      vascularized mediastinal masses. Resection of the mass, which is curative, is
      associated with a high risk of blood loss. Recently, preoperative arteriography
      with embolization has been used satisfactorily in the preoperative management of
      these tumors. We present a case of localized Castleman disease in a 12-year-old
      girl satisfactorily treated with embolization before curative resection.

PMID- 15989875
TI  - [Thoracic kaposiform hemangioendothelioma. Four consecutive cases with distinct
      outcome].
AB  - INTRODUCTION: Kaposiform hemangioendothelioma (KHE) is a rare, frequently
      congenital, neoplasm associated with the Kasabach-Merritt phenomenon (KMP) and
      predilection for the trunk. Its clinical course is unpredictable. A child with
      KHE can die as a result of hemorrhage or show early spontaneous regression. In
      addition various and concurrent therapies can be used to treat this tumor and it
      is difficult to predict which treatment will be successful. MATERIAL, METHODS AND
      RESULTS: We present four consecutive cases of KHE (larger than 20 cm) of the
      thorax. All patients developed KMP, without skin involvement in one patient.
      Patient 1, a neonate with KHE occupying both hemithoraces (nearly 50% of the body
      surface area), died shortly after birth due to coagulopathy and generalized
      bleeding. Patient 2, a neonate, was treated with interferon alpha-2a and showed
      accelerated correction of coagulopathy and complete tumoral regression at 9
      months. Patient 3 showed no response to steroids, interferon or vincristine
      therapy. Thrombocytopenia (platelet count 40,000) persisted for 8 years and was
      resolved by administration of aspirin plus ticlopidine, without tumoral
      disappearance. Patient 4 underwent incomplete removal of the tumor on her right
      chest wall after showing no response to antiangiogenic therapy. The coagulopathy
      persisted and a second radical surgical procedure resolved KMP. CONCLUSION: Given
      the variable response to pharmacological treatment and the scant possibilities of
      surgical resection, the management of KHE with KMP must include a
      multidisciplinary approach. As little is known about the pathogenesis of these
      highly aggressive vascular tumors, further molecular research is needed to
      understand their long-term behavior.

PMID- 15989877
TI  - [Tracheal laceration due to blunt neck trauma].

PMID- 15989876
TI  - [Nephrotic syndrome and Hodgkins disease, a rare association].

PMID- 15989878
TI  - [Necrotizing pneumonia complicated by empyema with slow resolution].

PMID- 15989879
TI  - [Pyogenic liver abscess in a healthy boy].

PMID- 15989880
TI  - [Benign afebrile convulsions due to rotavirus gastroenteritis].

PMID- 15989882
TI  - [Localized perforating serpiginous elastosis in a patient with Down syndrome].

PMID- 15989881
TI  - [Perinatal pelvic ectasia, the cascade effect and quaternary prevention].

PMID- 15989883
TI  - [Phlebectasia of the internal jugular vein].

PMID- 15989884
TI  - [Abrupt-onset generalized edema. Milk allergy].

PMID- 15989885
TI  - [The influence of specialty care on the management of hospitalized pneumonia].

PMID- 15989886
TI  - [Patients hospitalized with community-acquired pneumonia: a comparative study of
      outcomes by medical specialty area].
AB  - OBJECTIVE: Variability in the management of patients hospitalized with community
      acquired pneumonia (CAP) is attributable to many factors. The objective of this
      study was to determine whether such variability is influenced by the medical
      specialty area where the patient is treated. PATIENTS AND METHODS: The treatment
      and outcomes for a random sample of patients with CAP admitted to 4 hospitals
      over 2 periods (1 year starting March 1, 1998, and 1.5 years starting March 1,
      2000) were compared by medical specialty department. Multiple linear and logistic
      regression models were used to analyze differences. RESULTS: Differences were
      found between departments in the coverage of atypical pathogens (P<.001). The
      adjusted mean length of stay in hospital varied between 6.8 and 9.1 days (P<.01),
      and the duration of intravenous treatment varied between 4.6 and 7.3 days
      (P<.05). Adjusted models showed that mortality in hospital and at 30 days was
      significantly higher for patients treated in internal medicine departments (odds
      ratios, 2.1 and 2, respectively) than for those treated in pulmonology
      departments. CONCLUSIONS: Interdepartmental differences were observed in how
      patients hospitalized with CAP were treated and in the outcomes achieved. This
      variation is probably influenced by the differences that were found in the use of
      antibiotics.

PMID- 15989887
TI  - [Lung cancer at a university hospital: epidemiological and histological
      characteristics of a recent and a historical series].
AB  - OBJECTIVE: To describe the clinical, histological, and epidemiological
      characteristics of patients diagnosed with lung cancer in our hospital over a
      period of 5 years and compare them with those of historical cases treated at the
      same hospital. PATIENTS AND METHODS: The cases of patients diagnosed with lung
      cancer from January 1998 through December 2002 were studied retrospectively and
      compared with data published for the period from 1978 through March 1981.
      RESULTS: A total of 678 patients (89% men, mean age 67 years) were studied. Fifty
      six percent of the men and 38% of the women were smokers (P<.001). The most
      common histological types were squamous cell carcinoma (33%) and adenocarcinoma
      (30%): squamous carcinoma in men (36%) and adenocarcinoma in women (56%).
      Metastasis was present in 42% of the patients with non-small cell lung cancer and
      in 55% of those with small cell lung cancer. In patients with a history of
      neoplastic disease, laryngeal tumors were most common in patients with squamous
      carcinoma whereas bladder tumors were the most frequent in patients with
      adenocarcinoma. The ratio of men to women was lower in the recent series than in
      the historical one. The percentage of squamous carcinoma was lower and that of
      adenocarcinoma higher (P<.001). The percentage of patients diagnosed with
      regional involvement was greater in the recent series (P<.001). CONCLUSIONS:
      Squamous cell carcinoma continues to be the most frequent histological type. Male
      sex and smoking are associated with squamous carcinoma and female sex is
      associated with adenocarcinoma. Epidemiological and histological patterns have
      changed, possibly in relation to changes in smoking habits.

PMID- 15989888
TI  - [Cost and management of asthma exacerbations in Spanish hospitals (COAX study in
      hospital services)].
AB  - OBJECTIVE: The prevalence and associated health cost of asthma have been
      increasing in developed countries, and 70% of the overall disease cost is due to
      exacerbations. The primary objective of this study was to determine the hospital
      cost of an asthma exacerbation in Spain. The secondary objective was to determine
      what maintenance treatments patients were using to control asthma before the
      exacerbation and how the exacerbation was treated. The study formed part of a
      broader study (COAX II), with the same objectives in each of the 8 participating
      European countries. PATIENTS AND METHODS: Prospective observational study that
      enrolled 126 patients with an asthma exacerbation treated in the usual way in 6
      Spanish hospitals over a 3-month period (from January 1 to March 31, 2000).
      RESULTS: According to the criteria of the Global Initiative for Asthma, 33.3% of
      the exacerbations were mild, 38.9% moderate, 26.2% severe, and 1.6% were
      associated with risk of imminent respiratory arrest. Use of corticosteroids was
      widespread among patients with moderate and severe asthma, but only 68% of the
      patients with severe asthma used long-acting beta2 agonists. The mean cost was
      1555.70 Euros (95% confidence interval [CI], 1237.60 Euros-1907.00 Euros), of
      which 93.8% (1460.60 Euros; 95% CI, 1152.50 Euros-1779.40 Euros) was due to
      direct costs, and 6.2% (95.10 Euros; 95% CI, 35.50 Euros-177.00 Euros) to
      indirect costs. Cost rose with increasing severity of the exacerbation--292.60
      Euros for a mild exacerbation, 1230.50 Euros for a moderate exacerbation, and
      3543.10 Euros for a severe exacerbation. CONCLUSIONS: The mean cost was 1555.70
      Euros. The costs of moderate and severe exacerbations were 4 and 12 times that of
      a mild exacerbation, respectively. Long-acting beta2 agonists were less widely
      used than recommended by the guidelines for treatment of moderate and severe
      persistent asthma leading to asthma exacerbations.

PMID- 15989889
TI  - [Endoscopic treatment of central airway stenosis: five years' experience].
AB  - OBJECTIVE: To describe our experience with interventional bronchoscopy in the
      treatment of central airway stenosis. PATIENTS AND METHODS: We reviewed patient
      records and bronchoscopic findings. Clinical data, findings from computed
      tomography, techniques performed, complications, and results were recorded.
      RESULTS: One-hundred and thirty-six patients (90 males and 46 females) were
      treated. The mean (SD) age was 57 (7) years (range, 3-81). A total of 320
      therapeutic interventions were performed: 145 laser treatments, 33 balloon or
      mechanical dilatations, 26 electrocauterizations, and 116 stent insertions.
      Pathogenesis varied: in 64 (47%) patients, the stenosis was caused by a tumor (48
      were bronchopulmonary and 16 nonpulmonary); in 72 (53%) patients, stenosis was
      secondary to a nontumor-related process, of which the most common was prolonged
      intubation (42% of these cases). Central airway patency was achieved in 92%
      (59/64) of the tumor-related stenoses and 96% (69/72) of those unrelated to
      tumors. Improvement in dyspnea was observed in 96% of all patients. Two deaths
      (due to hemoptysis and to acute myocardial infarction) occurred in the first
      week, for a 1.4% mortality rate. The most common complications were stent
      migration (8%; 9/116 cases) and the formation of granulomas (9%; 11/116).
      CONCLUSIONS: Interventional bronchoscopy is an effective technique to resolve
      life-threatening obstructions of the central airways. Dyspnea improves
      immediately and there is no significant morbidity or mortality.

PMID- 15989890
TI  - [Bronchial exudate of serum proteins during asthma attack].
AB  - OBJECTIVE: Although altered vascular permeability and edema of the bronchial
      mucosa are associated with asthma attack, their influence on its severity remains
      unknown. We address this issue by comparing relative indices for the
      concentration of albumin (RIAlb) and alpha2-macroglobulin (RIalpha2M) in induced
      sputum and peripheral blood from patients with exacerbated asthma, patients with
      stable asthma, and control subjects. PATIENTS AND METHODS: Forty-six volunteers
      participated in the study: 14 with exacerbated asthma (forced expiratory volume
      in the first second [FEV1] 74.3% [SD, 20.8%] of reference), 23 with stable asthma
      (FEV1 93.6% [7.5%]), and 9 controls (FEV1 101.1% [9.9%]). The concentrations of
      albumin and alpha2-macroglobulin were quantified by immunoturbidimetry and
      immunonephelometry, respectively. The relative index was then calculated by
      dividing the concentration in sputum supernatant by the concentration in
      peripheral blood. RESULTS: The mean RIAlb was 1.2 (1.1) in the control group, 2.9
      (3.1) in the stable asthma group, and 6.0 (6.7) in the exacerbated asthma group.
      The RIalpha2M values were 11.7 (10.9), 11.9 (14.7), and 3.2 (3.8) for the control
      group and stable and exacerbated asthma groups, respectively. The increases in
      the RIAlb values between all groups, and the decrease in the RIalpha2M value
      between the exacerbated asthma and control groups were statistically significant
      (P<.05). The percentage of neutrophils, but not of eosinophils, in sputum was
      correlated with the RIAlb (r=0.39; P=.008) but not the RIalpha2M (r=-0.035;
      P=.82). FEV1 displayed an inverse relationship with the RIAlb (r=-0.43; P=.009)
      but not with the RIalpha2M (r=-0.206; P=.24). No correlation was found between
      oxyhemoglobin saturation and either the RIAlb (r=-0.33; P=.19) or the RIalpha2M
      (r=-0.12; P=.84). CONCLUSIONS: Vascular permeability is altered during asthma
      exacerbations and appears to be correlated with the presence of neutrophils and
      the degree of bronchial obstruction.

PMID- 15989891
TI  - [Attitude changes needed to foster treatment adherence in patients with asthma].

PMID- 15989893
TI  - [A minimally invasive technique to repair pectus carinatum. Preliminary report].
AB  - The present report deals with a new technique for the correction of pectus
      carinatum. Although less frequent than pectus excavatum, this deformity leads to
      numerous consultations, as it is difficult to conceal and affects the personality
      and behavior of many young patients. We report the case of a 13-year-old boy with
      asymmetrical pectus carinatum. The chest wall was compressible, so the protrusion
      was corrected by means of intrathoracic compression. In this technique, the
      sternochondral region is compressed by implanting a metal bar in the presternal
      region and securing it bilaterally to the posterolateral portion of the costal
      arches. The strut remains implanted until remolding of the chest contour is
      achieved. In this case, the strut was removed after 1 year and the new chest
      contour has been maintained unchanged more than 8 months following surgery. In
      conclusion, this minimally invasive technique for the treatment of pectus
      carinatum by means of intrathoracic compression appears to be a valid alternative
      to more invasive techniques and should be considered in appropriate cases.

PMID- 15989894
TI  - [Recurrent hemoptysis secondary to an aortobronchial fistula].
AB  - Aortobronchial fistula is a rare but serious cause of hemoptysis. It can develop
      from an aneurysm of the descending thoracic aorta in the context of infections or
      it may appear as a sequel of surgical repair of congenital heart defects.
      Presenting symptoms include mild bronchial hemorrhages and recurrent chest pain,
      culminating in a normally fatal massive hemorrhage. Diagnosis by imaging is not
      always conclusive and clinical suspicion based on medical history is essential.
      Surgical placement of an endovascular stent graft is the treatment of choice.
      Post-surgical prognosis is good although there is a risk of recurrence in the
      case of superinfection.

PMID- 15989895
TI  - [Necrotizing sarcoid granulomatosis].

PMID- 15989896
TI  - [Pulmonary infiltrates after initiation of treatment with infliximab for adult
      Still's disease].

PMID- 15989897
TI  - The answer you get depends on the question you ask.

PMID- 15989899
TI  - Update on the drug treatment of hypertension in patients with cardiovascular
      disease.
AB  - The management of the high-risk patient with hypertension has become more
      challenging in recent years. Drug therapy should be initiated earlier and at
      lower blood pressure levels in patients with coexisting cardiovascular or kidney
      diseases. The blood pressure goals of drug therapy are substantially lower when
      patients have concomitant heart or kidney disease or diabetes mellitus. Numerous
      clinical trials in tens of thousands of hypertensive patients with increased
      cardiovascular risk have demonstrated that the calcium antagonists are as
      effective and safe as diuretics, beta-adrenergic blockers, and renin-angiotensin
      blocking agents to prevent heart attack and stroke but not heart failure. Several
      recent studies also demonstrate that angiotensin-converting enzyme inhibitors and
      angiotensin-receptor blockers are effective in preventing stroke, progressive
      renal insufficiency, and heart failure in higher risk patients with hypertension.
      To achieve the aggressive blood pressure goals in patients with cardiovascular
      disease, thoughtful combinations of additive or synergistic agents improve
      efficacy and tolerability and have become an integral part of the modern
      management of hypertensive patients with coexisting cardiovascular disease.

PMID- 15989900
TI  - Amiodarone and the thyroid.
AB  - Among the drugs affecting the thyroid gland, no drug has puzzled, and at the same
      time fascinated, endocrinologists more than amiodarone. Amiodarone is a potent
      class III anti-arrhythmic drug that also possesses beta-blocking properties. It
      is very rich in iodine, with a 100-mg tablet containing an amount of iodine that
      is 250 times the recommended daily iodine requirement. Amiodarone produces
      characteristic alterations in thyroid function tests in euthyroid patients.
      Understanding these alterations is crucial in avoiding unnecessary investigations
      and treatment. Amiodarone-induced thyroid dysfunction occurs because of both its
      iodine content and the direct toxic effects of the compound on thyroid
      parenchyma. Amiodarone-induced hyperthyroidism is more common in iodine-deficient
      regions of the world, whereas amiodarone-induced hypothyroidism is usually seen
      in iodine-sufficient areas. In contrast to amiodarone-induced hypothyroidism,
      amiodarone-induced thyrotoxicosis is a difficult condition to diagnose and treat.
      In this review, we discuss the alterations in thyroid function tests seen in
      euthyroid subjects, the epidemiology and mechanism of amiodarone-induced thyroid
      dysfunction, treatment options available, and the consequences of amiodarone use
      in pregnancy and lactation; and finally, we propose a follow-up strategy in
      patients taking amiodarone.

PMID- 15989901
TI  - No walk in the park.

PMID- 15989902
TI  - Single coronary artery.

PMID- 15989903
TI  - Acute myocardial infarction.

PMID- 15989904
TI  - The rare needle in a diagnostic haystack.

PMID- 15989905
TI  - Low-dose aspirin increases aspirin resistance in patients with coronary artery
      disease.
AB  - PURPOSE: We sought to investigate the association of aspirin dose and aspirin
      resistance in stable coronary artery disease patients measured by a point-of-care
      assay. METHODS: We studied 468 consecutive stable coronary artery disease
      patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily
      for > or =4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San
      Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction
      unit (ARU) > or =550 indicates the absence of aspirin-induced platelet
      dysfunction, based on correlation with epinephrine-induced light transmission
      aggregometry. Demographic and clinical data were collected to analyze the
      predictors of aspirin resistance. RESULTS: Aspirin resistance was noted in 128
      (27.4%) patients. Univariate predictors of aspirin resistance include elderly (P
      = 0.002), women (P <0.001), anemia (P <0.001), renal insufficiency (P = 0.009)
      and aspirin dose < or =100 mg (P = 0.004). Multivariate analysis revealed
      hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P
      <0.001) and aspirin dose < or =100 mg (OR 2.23; 95% CI 1.12 to 4.44; P = 0.022)
      to be independent predictors of aspirin resistance. Daily aspirin dose < or = 100
      mg was associated with increased prevalence of aspirin resistance compared with
      150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). CONCLUSION: A 100 mg
      or less daily dose of aspirin, which may have lower side effects, is associated
      with a higher incidence of aspirin resistance in patients with coronary artery
      disease. Prospective randomized studies are warranted to elucidate the optimal
      aspirin dosage for preventing ischemic complications of atherothrombotic disease.

PMID- 15989906
TI  - Incidence and hospital death rates associated with heart failure: a community
      wide perspective.
AB  - PURPOSE: Despite often stated references to the emerging epidemic of heart
      failure in the United States, relatively little data are available describing the
      incidence and short-term death rates associated with this clinical syndrome. The
      objectives of this study were to describe the hospital incidence and death rates
      associated with acute heart failure and factors associated with an adverse
      hospital prognosis in residents of the Worcester, Mass, metropolitan area
      hospitalized at all greater Worcester medical centers with new onset heart
      failure in 2000. SUBJECTS AND METHODS: We reviewed the medical records of
      patients hospitalized for acute heart failure at all 11 area medical centers
      during 2000. New onset heart failure was diagnosed using standardized criteria.
      Regression analyses were performed to examine demographic and clinical factors
      associated with hospital death rates. RESULTS: During 2000, 2604 men and women
      from greater Worcester were diagnosed with new onset heart failure; 637 (24.5%)
      of these cases were initial events. The incidence and attack rates (per 100,000)
      of heart failure were 219 and 897, respectively. Occurrence of heart failure
      increased with advancing age, and women were at greater risk for heart failure
      than men (incidence rates [per 100,000] = 250 and 194, respectively). Hospital
      case-fatality rates were 5.1%. Hospital death rates were associated with several
      demographic and clinical characteristics. CONCLUSIONS: The results of this study
      suggest that heart failure is an important clinical syndrome affecting residents
      of this large northeast community. Several groups at high risk for developing or
      dying from heart failure can be identified and targeted for preventive efforts as
      well as for the receipt of effective treatment modalities.

PMID- 15989907
TI  - Aortic valve replacement in patients with mild or moderate aortic stenosis and
      coronary bypass surgery.
AB  - PURPOSE: To assess whether there is survival benefit for patients with mild or
      moderate aortic stenosis if they undergo aortic valve replacement at the time of
      coronary artery bypass surgery. METHODS: From 1985 to 1995 we evaluated all
      patients at our institution who underwent coronary artery bypass surgery and who
      had the echocardiographic diagnosis of mild (mean gradient <0 mm Hg and/or valve
      area >1.5 cm(2)) or moderate (mean gradient > or =30 and < or =40 mm Hg and/or
      valve area >1.0 < or =1.5 cm(2)) aortic stenosis. Using propensity analysis,
      survival was compared between 129 patients who underwent coronary artery bypass
      surgery alone and 78 patients who underwent concomitant coronary artery bypass
      surgery and aortic valve replacement. RESULTS: Perioperative mortality was
      similar among patients who underwent coronary artery bypass surgery alone
      compared with patients who underwent concomitant coronary artery bypass surgery
      and aortic valve replacement. By Kaplan-Meier analysis, 1-year and 8-year
      survival were better at 90% and 55% for patients who underwent concomitant
      coronary artery bypass surgery and aortic valve replacement compared with 85% and
      39% for patients who underwent coronary artery bypass surgery alone (P <0.001).
      This benefit was limited to patients with moderate aortic stenosis (propensity
      adjusted relative risk = 0.43; 95% confidence interval: 0.20 to 0.96; P = 0.04).
      CONCLUSION: Concomitant aortic valve replacement at the time of coronary artery
      bypass surgery for mild or moderate aortic stenosis appears to convey a survival
      advantage for patients with moderate aortic stenosis but not for those with mild
      aortic stenosis.

PMID- 15989908
TI  - Latin American randomized trial of balloon angioplasty vs coronary stenting for
      small vessels (LASMAL): immediate and long-term results.
AB  - PURPOSE: To assess the potential role of coronary stent to improved acute success
      and reduce late restenosis in lesions with reference diameter <2.9 mm using a
      bare metal stent specifically designed for small coronary vessels. There is
      controversy on the results among previous studies comparing bare metal stent
      implantation with conventional balloon percutaneous transluminal coronary
      angioplasty (PTCA). Differences in baseline characteristics, inclusion and
      exclusion criteria, and stent design may account for these discrepancies.
      METHODS: The population of this multicenter, multinational randomized study
      (LASMAL) consisted of 246 patients undergoing percutaneous coronary intervention
      of small vessel reference diameter. They were randomized into 2 strategies of
      percutaneous revascularization: elective primary stent (n = 124) or conventional
      balloon PTCA with provisional stenting (n = 122) in the presence of acute,
      threatened closure or flow-limiting dissections. RESULTS: The clinical success
      rate was significantly better for the stent group (98.3% vs 91.8%; P = 0.038). At
      30 days follow-up, requirements of target vessel revascularization (TVR) (6.6% vs
      0.8%; P = 0.018) and incidence of major adverse cardiac and cerebrovascular
      events (MACCE) (9.8% vs 2.4%; P = 0.01) was significantly lower in the stent
      strategy. Postpercutaneous coronary intervention minimal luminal diameter (MLD)
      was significantly larger in the stent group (2.3 +/- 0.2 mm vs 2.2 +/- 0.2 mm; P
      = 0.003). At follow-up, MLD in the stent group was larger than with PTCA (1.7 +/-
      0.7 mm vs 1.5 +/- 0.7 mm, respectively; P = 0.035). Net gain was also
      significantly better with stent strategy (1.1 +/- 0.7 mm vs 0.8 +/- 0.7 mm,
      respectively; P = 0.002). Stenting resulted in a significant lower angiographic
      binary restenosis (20% vs 31%; P = 0.02) than PTCA. Furthermore, patients treated
      with stent were more frequently free from MACCE at 9-month follow-up (death,
      acute myocardial infarction [AMI], stroke, repeat revascularization procedures)
      than those treated initially with PTCA (82.2% vs 72% of PTCA, P = 0.046).
      CONCLUSIONS: The use of a specifically designed bare metal coronary phosphoril
      choline-coated stent as primary device during percutaneous interventions in small
      coronary arteries was associated with high procedural success and low in-hospital
      and 30-day follow-up complications. At long-term follow-up, patients initially
      treated with stents had lower angiographic restenosis rate and were more
      frequently free from major adverse cardiac events.

PMID- 15989909
TI  - Recurrent infarction causes the most deaths following myocardial infarction with
      left ventricular dysfunction.
AB  - PURPOSE: The development of left ventricular systolic dysfunction or heart
      failure following an acute myocardial infarction (MI) is a powerful marker of an
      adverse prognosis. Recurrent MI could be an important cause of death, either
      directly or by provoking arrhythmias. METHODS: The OPTIMAAL trial randomized 5477
      patients with heart failure or evidence of left ventricular dysfunction following
      acute MI to losartan or captopril. Over a follow-up of 2.7 years, there were 946
      deaths. Of the 180 (19%) of these deaths for which autopsy reports were
      available, acute MI was found in 57% (102 of 180) of the autopsies. By
      comparison, an endpoints adjudication committee using clinical data attributed
      death to acute MI in only 29 cases. An acute MI was found at autopsy in 55% (37
      of 67) of the deaths that had been classified as due to an arrhythmia and in 81%
      (21 of 26) of the deaths classified as due to progressive heart failure.
      Including autopsy diagnoses, the rate of acute MI in patients who died suddenly
      was independent of the time elapsed since the index MI, but in patients not
      classified as dying suddenly, there was a time-related decrease in recurrent MI
      from 78% in the first 30 days to 30% by the end of follow-up. However, only 19%
      of patients who died underwent autopsy, so recurrent MI may have been
      substantially more common and perhaps had a different relation to time since the
      index MI if more patients had undergone autopsy. CONCLUSIONS: In patients with
      evidence of major cardiac dysfunction after MI, recurrent MI found at autopsy is
      common and has often not been clinically detected.

PMID- 15989910
TI  - Enterococcal endocarditis: 107 cases from the international collaboration on
      endocarditis merged database.
AB  - PURPOSE: To describe clinical features and outcomes of enterococcal left-sided
      native valve endocarditis and to compare it to endocarditis caused by other
      pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on
      Endocarditis-Merged Database were included if they had left-sided native valve
      endocarditis. Demographic characteristics, clinical features, and outcomes were
      analyzed. Multivariable analysis evaluated enterococcus as a predictor of
      mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis,
      107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently
      seen in elderly men, frequently involved the aortic valve, tended to produce
      heart failure rather than embolic events, and had relatively low short-term
      mortality. Compared to patients with non-enterococcal endocarditis, patients with
      enterococcal endocarditis had similar rates of nosocomial acquisition, heart
      failure, embolization, surgery, and mortality. Compared to patients with
      streptococcal endocarditis, patients with enterococcal endocarditis were more
      likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and
      have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to
      patients with S. aureus endocarditis, patients with enterococcal endocarditis
      were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and
      less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable
      analysis of all patients with left-sided native valve endocarditis showed that
      enterococcal endocarditis was associated with lower mortality (odds ratio [OR]
      0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal
      native valve endocarditis has a distinctive clinical picture with a good
      prognosis.

PMID- 15989911
TI  - Estimating the patient care costs of teaching in a teaching hospital.
AB  - PURPOSE: Because leaders at medical schools and teaching hospitals need current
      data to estimate the clinical costs of graduate medical education, the authors
      developed a new methodology to estimate the hospital costs associated with the
      presence of teaching physicians for the year 2002. METHOD: A hospital accounting
      system was used to determine the case mix-adjusted direct variable costs for
      41,522 inpatient admissions associated with or without a teaching physician.
      RESULTS: Prior to adjustment, teaching cases had greater median costs than non
      teaching cases. After severity adjustment, teaching cases in aggregate were
      associated with an additional 4.4% of the total direct variable cost of inpatient
      admissions, or US 3.6 million dollars. The size of the teaching effect varied by
      service, ranging from -5.7% for medical services to 13 percent for behavioral
      services. The effect of teaching on cost centers such as laboratory, pharmacy,
      and radiology varied by specialty service. Teaching was associated with a
      negligible 0.7% relative difference in length of stay. CONCLUSION: The
      incremental effects of teaching on hospital patient care costs are modest. These
      analyses can be repeated annually to detect changes in teaching costs and to
      target areas of excessive cost for interventions that improve efficiency. Our
      results and methods for identifying hospital costs associated with teaching
      services may prove useful in negotiations between academic health centers and
      affiliated teaching hospitals.

PMID- 15989912
TI  - Disciplinary action against physicians: who is likely to get disciplined?
AB  - PURPOSE: We sought to determine the characteristics of disciplined physicians at
      large and the risk of disciplinary action over time and to report the type and
      frequency of complaints and the nature of disciplinary actions against allopathic
      physicians in Oklahoma. METHODS: Descriptive statistics, Kaplan-Meier analysis,
      and Cox proportional hazards modeling of publicly available data on physicians
      licensed by the Oklahoma Board of Medical Licensure and Supervision. RESULTS:
      Among 14,314 currently or previously licensed physicians, 396 (2.8%) had been
      disciplined. Using univariate proportional hazards analysis, men (P <0.04), non
      whites (P < 0.001), non-board-certified physicians (P < 0.001), and those in
      family medicine (P < 0.001), psychiatry (P < 0.001), general practice (P <
      0.001), obstetrics-gynecology (P < 0.03) and emergency medicine (P < 0.001) were
      found to be at greater risk of being disciplined than other medical specialty
      groups. Foreign medical graduates had a higher risk of disciplinary action
      compared to US medical graduates (P < 0.001), although this finding was not
      confirmed by multivariate analysis. Kaplan-Meier analysis revealed that the
      proportion of physicians disciplined increased with each successive 10-year
      interval since first licensure. Complaints against physicians originated most
      often from the general public (66%), other physicians (5%), and staff (4%), and
      the complaints most frequently involved issues related to quality of care (25%),
      medication/prescription violations (19%), incompetence (18%), and negligence
      (17%). CONCLUSION: To improve physician behavior and reduce the need for
      disciplinary action, medical schools and residency training programs must
      continue to emphasize both patient care and medical professionalism as critical
      core competencies.

PMID- 15989913
TI  - Effects of proton pump inhibitors on calcium carbonate absorption in women: a
      randomized crossover trial.

PMID- 15989914
TI  - Idiopathic retroperitoneal fibrosis associated with immunohematological
      abnormalities.

PMID- 15989915
TI  - Walt Whitman, Civil War nurse.

PMID- 15989916
TI  - Perceived impact of duty hours limits on the fragmentation of patient care:
      results from an academic health center.

PMID- 15989917
TI  - Painless right hemorrhagic pleural effusions as presentation sign of aortic
      dissecting aneurysm.

PMID- 15989918
TI  - Candida tropicalis osteomyelitis: case report and review of literature.

PMID- 15989919
TI  - Synovial neurofibromatosis in von Recklinghausen's disease.

PMID- 15989920
TI  - Utility of PCR in diagnosing complicated cases of unusual clinical manifestations
      of Salmonella enterica var. paratyphi A.

PMID- 15989921
TI  - In response to Business and Research.

PMID- 15989922
TI  - Increasing perioperative beta-blocker utilization: a successful quality
      improvement project.

PMID- 15989923
TI  - Mild trimethylaminuria observed in a Japanese cohort with liver damage.

PMID- 15989924
TI  - Patient-relevant, rather than physician-friendly, definitions of disease: an
      improved definition of epilepsy.

PMID- 15989925
TI  - Acquired factor V inhibitor: a common and avoidable complication of topical
      bovine thrombin application.

PMID- 15989926
TI  - Separation of keratan-sulfate-derived disaccharides by high-performance liquid
      chromatography and postcolumn derivatization with 2-cyanoacetamide and
      fluorimetric detection.
AB  - In this paper, we report a rapid, sensitive, and quantitative procedure to
      conduct disaccharide compositional analyses of keratan sulfates (KS) by means of
      high-performance liquid chromatography (HPLC) separation and postcolumn
      derivatization with 2-cyanoacetamide and fluorimetric detection of products
      generated by hydrolysis of this glycosaminoglycan with Bacillus sp. keratanase II
      or Escherichia freundii endo-beta-galactosidase. Following E. freundii endo-beta
      galactosidase digestion of bovine corneal KS, the monosulfated disaccharide
      glcNAc6sbeta(1-->3)gal, accounting for approximately equals 95% nmol and 50%
      yield products, is produced. On the contrary, bovine corneal KS treated with endo
      beta-N-acetylglucosaminidase (keratanase II) from Bacillus sp. generates two
      major products, the monosulfated disaccharide galbeta(1-->4)glcNAc6s (
      approximately equals 50% nmol product) and the disulfated disaccharide
      gal6sbeta(1-->4)glcNAc6s ( approximately equals 40% nmol product) for over 90%
      nmol products. These disaccharides are separated and readily determined within 30
      min by using a linear-gradient strong anion-exchange separation. A linear
      relationship was found for the two purified disaccharides over a wide range of
      concentrations, from approximately equals 108 pmol, 50 ng, to 2,160 pmol, 1,000
      ng, for the disaccharide galbeta(1-->4)glcNAc6s, and from 92 pmol, 50 ng, to
      1,840 pmol, 1,000 ng, for the disaccharide gal6sbeta(1-->4)glcNAc6s. HPLC
      analysis was applied to the quantitative and qualitative determination of KS
      produced by 3T3-J2 murine fibroblasts in the cell medium. The amount of KS was
      found to be 2.80+/-0.34 microg/ml/10(6) cells and composed of approximately
      equals 71% nmol of disaccharide galbeta(1-->4)glcNAc6s and 18% nmol of the
      disulfated disaccharide gal6sbeta(1-->4)glcNAc6s having approximately equals 1.20
      sulfate groups/disaccharide. Our data illustrate that the HPLC procedure reported
      represents an improved approach for the quantitative and compositional
      microanalyses of KS, especially applicable to experimentation involving small
      amounts ( approximately 50 ng) of this glycosaminoglycan and in relation to its
      biological function and pathological importance.

PMID- 15989927
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      protocol for monitoring the progress of enzymatic (13)C/(15)N-labeled DNA
      syntheses.
AB  - We demonstrate that a simple matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometry protocol provides a rapid and accurate
      method for monitoring the stage and completeness of enzymatic DNA syntheses. A
      crucial step of these syntheses is to quench the reaction at the desired
      nucleotide length. This is especially important when expensive, e.g., (13)C/(15)N
      labeled DNA segments, are synthesized for multinuclear magnetic resonance
      purposes to reveal detailed structural information. The analyses of three
      templates for a human telomeric 22-mer, a wild type, and a mutant human c-MYC
      promoter (18- and 22-mer) DNA and their reactions with the 3'-5' exo(-) Klenow
      fragment of DNA polymerase I demonstrate the usefulness of our protocol. Small
      amounts of samples (ca. 1-2 microl each) were taken from the reaction mixtures at
      different times and analyzed promptly by MALDI-TOF, applying our successive on
      plate desalting method that eliminates the insensitivity of the MALDI technique
      at high salt content. The progress of the reaction was detected by monitoring the
      relative intensity ratios of ions corresponding to the desired products and the
      primer-template complexes. The effectiveness of NH(3) cleavage leading to final
      products was also followed by MALDI-TOF in successful enzymatic reactions.

PMID- 15989928
TI  - Fluorescein chemiluminescence method for estimation of membrane permeability of
      liposomes.

PMID- 15989929
TI  - A quantitative method for normalization of transfection efficiency using enhanced
      green fluorescent protein.

PMID- 15989930
TI  - Simultaneous determination of ubiquinol and ubiquinone in skeletal muscle of
      pediatric patients.

PMID- 15989931
TI  - Northerns revisited: a protocol that eliminates formaldehyde from the gel while
      enhancing resolution and sensitivity.

PMID- 15989932
TI  - Self-ordered pointing in children with autism: failure to use verbal mediation in
      the service of working memory?
AB  - This study tested the hypothesis that children with autism are impaired in using
      verbal encoding and rehearsal strategies in the service of working memory.
      Participants were 24 high-ability, school-age children with autism and a
      comparison group matched on verbal and non-verbal IQ, receptive and expressive
      vocabulary, and visual memory. Working memory was assessed using verbal and non
      verbal variants of a non-spatial, self-ordered pointing test [Petrides, M., &
      Milner, B. (1982). Deficits on subject-ordered tasks after frontal- and temporal
      lobe lesions in man. Neuropsychologia, 20, 249-262] in which children had to
      point to a new stimulus in a set upon each presentation without repeating a
      previous choice. In the verbal condition, the stimuli were pictures of concrete,
      nameable objects, whereas in the non-verbal condition, the stimuli were not
      easily named or verbally encoded. Participants were also administered a verbal
      span task to assess non-executive verbal rehearsal skills. Although the two
      groups were equivalent in verbal rehearsal skills, the autism group performed
      significantly less well in the verbal, but not the non-verbal, self-ordered
      pointing test. These findings suggested that children with autism are deficient
      in the use of verbal mediation strategies to maintain and monitor goal-related
      information in working memory. The findings are discussed in terms of possible
      autistic impairments in episodic memory as well as working memory.

PMID- 15989933
TI  - Visual letter matching: hemispheric functioning or scanning biases?
AB  - Finding two mixed-case letters that share the same name is easier to do when the
      letters are presented in opposite visual fields than when they are both in the
      same field. By contrast, finding a match between two same-case letters is easier
      when they are in the same field. These visual field effects have been attributed
      to the ability of the corpus callosum to coordinate the work of the cerebral
      hemispheres [Banich, M. T. (1998). The missing link: The role of interhemispheric
      interaction in attentional processing. Brain and Cognition, 36, 128-157;
      Weissman, D. H., & Banich, M. T. (2000). The cerebral hemispheres cooperate to
      perform complex but not simple tasks. Neuropsychology, 14, 41-59]. The present
      study considers the alternative hypothesis that attentional scanning biases may
      be at work. Experiment 1 examined the effects of explicit instructions to scan
      items in a specific order; Experiment 2 examined influences of implicit location
      biasing; Experiment 3 considered the possibility that same-case letter matching
      is different because a perceptual grouping mechanism can be used in that task. In
      each experiment, we first interpreted the results within the hemispheric
      framework before considering the alternative accounts. We concluded that two
      scanning biases may be in effect: (1) an automatic bias favoring items in
      locations relatively distant from the current focus of attention and (2) a
      learned bias to scan letters in a left-to-right direction.

PMID- 15989934
TI  - Emotional content and reality-monitoring ability: fMRI evidence for the
      influences of encoding processes.
AB  - Memory for emotional items can be less prone to some types of memory distortion,
      such as reality-monitoring errors, than memory for neutral items. The present
      fMRI study examined whether this enhanced reality-monitoring accuracy reflects
      engagement of distinct processes recruited during encoding of emotional
      information. Participants only imagined named objects (word-only trials) or
      imagined named objects and then also viewed photos of them (word-picture trials).
      Half of the items were emotional (e.g., snake, casket). Later, participants heard
      object names and indicated whether the corresponding photo had been shown.
      Reality-monitoring errors occurred when participants attributed an item from a
      word-only trial to a word-picture trial. Such misattribution errors occurred less
      frequently for emotional than neutral items. Activity in emotion-processing
      regions (e.g., orbitofrontal cortex, amygdala) reduced the likelihood of later
      misattributions, likely due in part to interactions with regions that promote
      memory accuracy (e.g., the hippocampus). Distinct neural processes also increased
      the likelihood of reality-monitoring errors, depending on the emotional content
      of the items. Activity spanning the fusiform and parahippocampal gyri (likely
      reflecting mental imagery) increased the likelihood of reality-monitoring errors
      for neutral items, while activity in the anterior cingulate increased the
      likelihood of reality-monitoring errors for emotional items.

PMID- 15989935
TI  - Sustained involvement of a frontal-parietal network for spatial response
      selection with practice of a spatial choice-reaction task.
AB  - With practice, performance on a task typically becomes faster, more accurate, and
      less prone to interference from competing tasks. Some theories of this
      performance change suggest it reflects a qualitative reorganization of the
      cognitive processing required for successful task performance. Other theories
      suggest this change in performance reflects a more quantitative change in the
      amount of processing required to perform the task. Neuroimaging research results
      provide some support for both of these broad theories. This inconsistency may
      reflect the complex nature of the effect of practice on cognitive and neural
      processing. Our current experiment addresses this issue by investigating the
      effect of practice of a relatively easy perceptual-motor task on the frontal
      parietal brain network for a specific cognitive process (viz. spatial response
      selection). Participants were scanned during three functional magnetic resonance
      imaging sessions on separate days within 4 days while they performed a relatively
      easy spatial perceptual-motor task. We found sustained activity with practice in
      right dorsal prefrontal cortex; and sustained but decreasing activity in
      bilateral dorsal premotor, left superior parietal, and precuneus cortices,
      supporting a quantitative decrease in difficulty of response selection with
      practice. Conversely, we found a qualitative change in activity with practice in
      left dorsal prefrontal cortex. This brain region is outside the response
      selection network for this task and showed activity only during novel task
      performance. These results suggest that practice produces both qualitative and
      quantitative changes in processing. The particular effect of practice depends on
      the cognitive process in question.

PMID- 15989936
TI  - Perceptual-motor skill learning in Gilles de la Tourette syndrome. Evidence for
      multiple procedural learning and memory systems.
AB  - Procedural learning and memory systems likely comprise several skills that are
      differentially affected by various illnesses of the central nervous system,
      suggesting their relative functional independence and reliance on differing
      neural circuits. Gilles de la Tourette syndrome (GTS) is a movement disorder that
      involves disturbances in the structure and function of the striatum and related
      circuitry. Recent studies suggest that patients with GTS are impaired in
      performance of a probabilistic classification task that putatively involves the
      acquisition of stimulus-response (S-R)-based habits. Assessing the learning of
      perceptual-motor skills and probabilistic classification in the same samples of
      GTS and healthy control subjects may help to determine whether these various
      forms of procedural (habit) learning rely on the same or differing
      neuroanatomical substrates and whether those substrates are differentially
      affected in persons with GTS. Therefore, we assessed perceptual-motor skill
      learning using the pursuit-rotor and mirror tracing tasks in 50 patients with GTS
      and 55 control subjects who had previously been compared at learning a task of
      probabilistic classifications. The GTS subjects did not differ from the control
      subjects in performance of either the pursuit rotor or mirror-tracing tasks,
      although they were significantly impaired in the acquisition of a probabilistic
      classification task. In addition, learning on the perceptual-motor tasks was not
      correlated with habit learning on the classification task in either the GTS or
      healthy control subjects. These findings suggest that the differing forms of
      procedural learning are dissociable both functionally and neuroanatomically. The
      specific deficits in the probabilistic classification form of habit learning in
      persons with GTS are likely to be a consequence of disturbances in specific
      corticostriatal circuits, but not the same circuits that subserve the perceptual
      motor form of habit learning.

PMID- 15989937
TI  - Task-related activity in prefrontal cortex and its relation to recognition memory
      performance in young and old adults.
AB  - Older adults often have more widespread prefrontal cortex (PFC) activation during
      memory retrieval tasks, compared to young adults, particularly in the left
      hemisphere. Recruitment of additional frontal activity in older adults has been
      attributed by some researchers to compensation, perhaps for reduced activity
      elsewhere in the brain, whereas others have described it as a non-selective
      response that may be due to a failure to inhibit these PFC regions. To address
      further the impact of PFC activity on memory in older adults, we used PET to
      measure brain activity during recognition memory tasks. Both young and old adults
      showed increased activity during recognition, compared to a control task, in
      bilateral PFC. Young adults showed greater activation of left hippocampus and
      lateral temporal cortex during recognition, whereas older adults showed greater
      activity in the right inferior frontal gyrus. Age differences also were seen in
      correlations between brain activity and memory performance. There were positive
      correlations between activity in the right parahippocampal gyrus and recognition
      performance in young adults, whereas positive correlations between activity in
      PFC and performance were found only in older adults. These positive correlations
      included the right inferior PFC region where older adults had greater activation.
      Activity in this right PFC region was negatively correlated with medial temporal
      activity in both groups. These results provide further evidence for age-specific
      patterns of brain activity underlying memory performance and are consistent with
      the idea that PFC assumes a larger role in supporting successful recognition
      memory with increasing age. The negative correlation between activity in PFC and
      medial temporal regions, as well as the age differences in how these regions were
      related to behavior, suggest that those older individuals who recruit PFC to a
      greater degree may do so as a compensatory response to reductions in medial
      temporal regions.

PMID- 15989938
TI  - Semantic memory in partial epilepsy: verbal and non-verbal deficits and
      neuroanatomical relationships.
AB  - Semantic memory was evaluated in 124 epilepsy patients, including 84 with left
      (n=44) or right temporal lobe epilepsy (TLE) (n=40) and 40 with left (n=25) or
      right frontal lobe epilepsy (FLE) (n=15), in order to determine their verbal and
      visual deficits, and the neuroanatomical relationships between them. The controls
      were 35 healthy subjects. Semantic memory was assessed by means of Picture
      Naming, Picture Pointing, the verbal Pyramid and Palm Trees Test (PPTT), the
      visual PPTT, Object Decision Hard, and Drawing From Memory. Episodic memory was
      assessed by means of the Short Story, Rey's Complex Figure, the Verbal and Visual
      Selective Reminding Procedure and Brown-Peterson Procedure. Factor analysis of
      the epilepsy patients distinguished their semantic memory scores from other
      neuropsychological domains. The semantic memory factor was significantly related
      to the side of the epileptic region, with lower scores in the left hemisphere and
      left TLE patients. In comparison with the controls, the left TLE patients were
      significantly impaired on Picture Naming, Picture Pointing, and Object Decision
      Hard. Subsequent analyses showed that, in comparison with the controls and the
      right TLE patients, the left TLE patients with lateral temporal lobe lesions were
      impaired in Picture Naming whereas, in comparison with the controls, the left TLE
      patients with mesial temporal lobe lesions were impaired in Object Decision Hard.
      On the contrary, the episodic memory factor was not related to the side of the
      epileptic region, and a few material-specific tests revealed opposite impairments
      in the left and right hemisphere patients. These results show that left TLE may
      cause semantic memory deficits involving verbal and visual information. Unlike
      the material-specific pattern of episodic memory, this pattern of impairment is
      in line with the view of an amodal semantic store in which all of the information
      about a thing overlaps. The semantic memory impairment may reflect damage in the
      lateral and mesial temporal lobe regions that impair neocortical functions in
      storing and retrieving information or hippocampal functions in processing
      meaningful stimuli.

PMID- 15989939
TI  - Visual memory loss and autobiographical amnesia: a case study.
AB  - Amnesia typically results from trauma to the medial temporal regions that
      coordinate activation among the disparate areas of cortex that represent the
      information that make up autobiographical memories. We proposed that amnesia
      should also result from damage to these regions, particularly regions that
      subserve long-term visual memory [Rubin, D. C., & Greenberg, D. L. (1998). Visual
      memory-deficit amnesia: A distinct amnesic presentation and etiology. Proceedings
      of the National Academy of Sciences of the USA, 95, 5413-5416]. We previously
      found 11 such cases in the literature, and all 11 had amnesia. We now present a
      detailed investigation of one of these patients. M.S. suffers from long-term
      visual memory loss along with some semantic deficits; he also manifests a severe
      retrograde amnesia and moderate anterograde amnesia. The presentation of his
      amnesia differs from that of the typical medial-temporal or lateral-temporal
      amnesic; we suggest that his visual deficits may be contributing to his
      autobiographical amnesia.

PMID- 15989940
TI  - Disconnection agraphia in a case of multiple sclerosis: the isolation of letter
      movement plans from language.
AB  - We report the case of a left-handed man (MCR), who presented with a peripheral
      agraphia as an early sign of multiple sclerosis. His left-handed writing was
      neologistic, whilst oral spelling, typing and spelling with the right hand were
      intact. Structural MRI scanning revealed a lesion of the body of the corpus
      callosum. Dichotic listening tests indicated that MCR displayed left hemisphere
      dominance for language. It is proposed that MCR represents a case of a
      disconnection syndrome in which right hemisphere systems that provide the basis
      for movement templates during left-handed writing are isolated from left
      hemisphere language systems. Analysis of left-handed writing indicated that
      peripheral movement control was highly structured with both individual letter
      frequency and sequential dependencies between letters represented within these
      motor control units. This case represents an opportunity to explore the
      mechanisms of movement control for writing and to examine the characteristics of
      isolated letter templates.

PMID- 15989941
TI  - Modulation of brain activity by selective task sets observed using event-related
      potentials.
AB  - We investigated the ability of subjects to shift dynamically between selective
      task sets, using informative trial-by-trial cues. Two tasks were used which
      involved non-overlapping neural systems and different hemispheric specialization.
      In a verbal task, subjects decided whether a letter string was a real word or a
      non-word. In a spatial task, subjects decided whether an angle was acute or
      obtuse. A behavioural experiment showed that performance improved when cues
      predicted the upcoming task (80% validity), compared to when neutral cues did not
      afford selective task sets. Event-related potentials (ERPs) revealed brain
      activity related to forming selective task expectations, to switching tasks, and
      to the modulation of target processing as a function of such expectations and
      switches. Activity predicting the probable task started over parietal electrodes
      160 ms after cue presentation, while activity related to task switching started
      at frontal electrodes around 280 ms. Both types of activities developed before
      target onset. Target processing was significantly influenced by the validity of
      the cue prediction, including strong modulation of language-related potentials.
      These results show that it is possible to switch dynamically between task sets
      involving distinct neural systems, even before the appearance of an imperative
      target stimulus, and that the nature of the task sets can influence neural
      activity related to task-set reconfiguration. Selective task sets can in turn
      modulate the processing of target stimuli. The effects also apply to the case of
      foveally presented words, whose processing has often been hypothesized to be
      automatic and outside the influence of selective attention.

PMID- 15989942
TI  - A transfer appropriate processing approach to investigating implicit memory for
      emotional words in the cerebral hemispheres.
AB  - Forty undergraduate students participated in two experiments designed to
      investigate the impact of perceptual and conceptual encoding manipulations on
      implicit memory for emotional words in each cerebral hemisphere. Adopting a
      transfer appropriate processing approach, the encoding manipulations were
      designed to promote processing of the surface features of stimuli in Experiment
      1, and their semantic meaning in Experiment 2. In both experiments, participants
      completed the designated encoding task, followed by a lexical decision task where
      primed and unprimed words were presented to the left (LVF) and right visual
      fields (RVF). In Experiment 1, implicit memory was observed for RVF presentations
      of words primed according to their perceptual features. Word valence did not
      impact on visual field of presentation for primed or unprimed words. In
      Experiment 2, participation in the conceptual encoding task differentially
      impacted on processing and implicit memory for emotional words presented in the
      LVF, where priming the conceptual meaning of words facilitated the processing of
      positive, relative to negative and non-emotional words. In addition, implicit
      memory for conceptually primed negative words was reflected in inhibition of
      primed relative to unprimed negatively valenced words presented in the LVF. In
      contrast, for RVF presentations, there was evidence of implicit memory for
      conceptually primed non-emotional words, but not for emotional words. The results
      are generally consistent with the right hemisphere model of emotion, which posits
      greater right hemisphere involvement in both the processing and implicit memory
      of emotional stimuli. The results also support Nagae and Moscovitch's suggestion
      [Nagae, S., & Moscovitch, M. (2002). Cerebral hemispheric differences in memory
      of emotional and non-emotional words in normal individuals. Neuropsychologia, 40,
      1601-1607] that level of processing be incorporated into studies examining the
      veracity of the right hemisphere and valence models of emotional processing. The
      study demonstrated the usefulness of adopting a transfer appropriate processing
      approach to investigating memory for word valence in each hemisphere.

PMID- 15989943
TI  - The hands and feet of Archaeolemur: metrical affinities and their functional
      significance.
AB  - Recent expeditions to Madagascar have recovered abundant skeletal remains of
      Archaeolemur, one of the so-called "monkey lemurs" known from Holocene deposits
      scattered across the island. These new skeletons are sufficiently complete to
      permit reassembly of entire hands and feet--postcranial elements crucial to
      drawing inferences about substrate preferences and positional behavior.
      Univariate and multivariate analysis of intrinsic hand and foot proportions,
      phalangeal indices, relative pollex and hallux lengths, phalangeal curvature, and
      distal phalangeal shape reveal a highly derived and unique morphology for an
      extinct strepsirrhine that diverges dramatically from that of living lemurs and
      converges in some respects on that of Old World monkeys (e.g., mandrills, but not
      baboons or geladas). The hands and feet of Archaeolemur are relatively short
      (extremely so relative to body size); the carpus and tarsus are both "long"
      relative to total hand and foot lengths, respectively; phalangeal indices of both
      the hands and feet are low; both pollex and hallux are reduced; the apical tufts
      of the distal phalanges are very broad; and the proximal phalanges are slightly
      curved (but more so than in baboons). Overall grasping capabilities may have been
      compromised to some extent, and dexterous handling of small objects seems
      improbable. Deliberate and noncursorial quadrupedalism was most likely practiced
      on both the ground and in the trees. A flexible locomotor repertoire in
      conjunction with a eurytopic trophic adaptation allowed Archaeolemur to inhabit
      much of Madagascar and may explain why it was one of the latest surviving
      subfossil lemurs.

PMID- 15989944
TI  - Life, death, and ubiquitin: taming the mule.
AB  - Ubiquitin-mediated protein degradation is an efficient way for the cell to get
      rid of unwanted proteins. A key player in this process is the E3 ubiquitin
      ligase. In this issue of Cell, and describe a new E3 ligase, ARF-BP1/Mule, which
      targets two very different substrates, p53 and Mcl-1, with completely different
      cellular outcomes.

PMID- 15989945
TI  - A disulfide relay system in mitochondria.
AB  - In this issue of Cell, show that there is a disulfide relay system in the
      intermembrane space (IMS) of mitochondria that is comprised of the proteins Mia40
      and Erv1. This disulfide relay system promotes the import and oxidative folding
      of proteins. Oxidized Mia40 traps newly imported proteins through mixed disulfide
      bridges. Subsequent isomerization of these disulfide bridges allows the imported
      protein to be folded in the IMS. The reduced Mia40 generated is then reoxidized
      by the sulfhydryl oxidase Erv1, promoting the next round of disulfide exchange.
      The new work clarifies the molecular function of Mia40 and reveals Mia40 to be
      the first physiological substrate for the FAD-linked Erv1.

PMID- 15989946
TI  - Stem cell grand SLAM.
AB  - Stem cells in both embryonic and adult tissues are defined by their unique
      ability to balance self-renewal and differentiation such that mature cells
      necessary for tissue function can be generated and replaced without depletion of
      the stem cell pool. In this issue of Cell, report a major step forward for
      studying the mechanisms and regulation of such stem cell fate decisions in the
      blood-forming (hematopoietic) system by providing a simple and broadly applicable
      method to isolate these cells and to visualize them in their normal environment.

PMID- 15989947
TI  - A new FronTIR in targeted protein degradation and plant development.
AB  - Three papers, two in a recent issue of Nature and one in the July issue of
      Developmental Cell, identify a family of F box proteins as the long-sought
      receptors for the plant growth hormone auxin. The new studies reveal that auxin,
      a small molecule, regulates F box proteins, which are involved in ubiquitin
      mediated protein degradation. This finding has profound implications for
      understanding plant physiology and development and for defining new modes of
      regulation of SCF ubiquitin ligase complexes.

PMID- 15989948
TI  - Complicated tails: histone modifications and the DNA damage response.
AB  - In recent years, several ATP-dependent chromatin-remodeling complexes and
      covalent histone modifications have been implicated in the response to double
      stranded DNA breaks (DSBs). When a DSB occurs, cells must identify the DSB,
      activate the DNA damage checkpoint, and repair the break. Chromatin modification
      appears to be important but not essential for each of these processes, yet its
      precise mechanistic roles are only beginning to come into focus. Here, we discuss
      the role of chromatin in signaling by the DNA damage checkpoint pathway.

PMID- 15989949
TI  - IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation
      that promotes chemical hepatocarcinogenesis.
AB  - IkappaB kinase beta (IKKbeta), required for NF-kappaB activation, links chronic
      inflammation with carcinogenesis. We investigated whether IKKbeta is involved in
      chemically induced liver cancer, a model not involving overt inflammation.
      Surprisingly, mice lacking IKKbeta only in hepatocytes (Ikkbeta(Deltahep) mice)
      exhibited a marked increase in hepatocarcinogenesis caused by diethylnitrosamine
      (DEN). This correlated with enhanced reactive oxygen species (ROS) production,
      increased JNK activation, and hepatocyte death, giving rise to augmented
      compensatory proliferation of surviving hepatocytes. Brief oral administration of
      an antioxidant around the time of DEN exposure blocked prolonged JNK activation
      and compensatory proliferation and prevented excessive DEN-induced carcinogenesis
      in Ikkbeta(Deltahep) mice. Decreased hepatocarcinogenesis was also found in mice
      lacking IKKbeta in both hepatocytes and hematopoietic-derived Kupffer cells.
      These mice exhibited reduced hepatocyte regeneration and diminished induction of
      hepatomitogens, which were unaltered in Ikkbeta(Deltahep) mice. IKKbeta,
      therefore, orchestrates inflammatory crosstalk between hepatocytes and
      hematopoietic-derived cells that promotes chemical hepatocarcinogenesis.

PMID- 15989950
TI  - Structural basis for the function of the ribosomal L7/12 stalk in factor binding
      and GTPase activation.
AB  - The L7/12 stalk of the large subunit of bacterial ribosomes encompasses protein
      L10 and multiple copies of L7/12. We present crystal structures of Thermotoga
      maritima L10 in complex with three L7/12 N-terminal-domain dimers, refine the
      structure of an archaeal L10E N-terminal domain on the 50S subunit, and identify
      these elements in cryo-electron-microscopic reconstructions of Escherichia coli
      ribosomes. The mobile C-terminal helix alpha8 of L10 carries three L7/12 dimers
      in T. maritima and two in E. coli, in concordance with the different length of
      helix alpha8 of L10 in these organisms. The stalk is organized into three
      elements (stalk base, L10 helix alpha8-L7/12 N-terminal-domain complex, and L7/12
      C-terminal domains) linked by flexible connections. Highly mobile L7/12 C
      terminal domains promote recruitment of translation factors to the ribosome and
      stimulate GTP hydrolysis by the ribosome bound factors through stabilization of
      their active GTPase conformation.

PMID- 15989951
TI  - Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity
      and metal-dependent catalysis.
AB  - RNase H belongs to a nucleotidyl-transferase superfamily, which includes
      transposase, retroviral integrase, Holliday junction resolvase, and RISC nuclease
      Argonaute. We report the crystal structures of RNase H complexed with an RNA/DNA
      hybrid and a mechanism for substrate recognition and two-metal-ion-dependent
      catalysis. RNase H specifically recognizes the A form RNA strand and the B form
      DNA strand. Structure comparisons lead us to predict the catalytic residues of
      Argonaute and conclude that two-metal-ion catalysis is a general feature of the
      superfamily. In nucleases, the two metal ions are asymmetrically coordinated and
      have distinct roles in activating the nucleophile and stabilizing the transition
      state. In transposases, they are symmetrically coordinated and exchange roles to
      alternately activate a water and a 3'-OH for successive strand cleavage and
      transfer by a ping-pong mechanism.

PMID- 15989952
TI  - Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control
      of a protein machine.
AB  - ATP hydrolysis by AAA+ ClpX hexamers powers protein unfolding and translocation
      during ClpXP degradation. Although ClpX is a homohexamer, positive and negative
      allosteric interactions partition six potential nucleotide binding sites into
      three classes with asymmetric properties. Some sites release ATP rapidly, others
      release ATP slowly, and at least two sites remain nucleotide free. Recognition of
      the degradation tag of protein substrates requires ATP binding to one set of
      sites and ATP or ADP binding to a second set of sites, suggesting a mechanism
      that allows repeated unfolding attempts without substrate release over multiple
      ATPase cycles. Our results rule out concerted hydrolysis models involving
      ClpX(6)*ATP(6) or ClpX(6)*ADP(6) and highlight structures of hexameric AAA+
      machines with three or four nucleotides as likely functional states. These
      studies further emphasize commonalities between distant AAA+ family members,
      including protein and DNA translocases, helicases, motor proteins, clamp loaders,
      and other ATP-dependent enzymes.

PMID- 15989953
TI  - Loops in the central channel of ClpA chaperone mediate protein binding,
      unfolding, and translocation.
AB  - The cylindrical Hsp100 chaperone ClpA mediates ATP-dependent unfolding of
      substrate proteins bearing "tag" sequences, such as the 11-residue ssrA sequence
      appended to proteins translationally stalled at ribosomes. Unfolding is coupled
      to translocation through a central channel into the associating protease, ClpP.
      To explore the topology and mechanism of ClpA action, we carried out chemical
      crosslinking and functional studies. Whereas a tag from RepA protein crosslinked
      proximally to the flexible N domains, the ssrA sequence in GFP-ssrA crosslinked
      distally in the channel to a segment of the distal ATPase domain (D2). Single
      substitutions placed in this D2 loop, and also in two apparently cooperating
      proximal (D1) loops, abolished binding of ssrA substrates and unfolded proteins
      lacking tags and blocked unfolding of GFP-RepA. Additionally, a substitution
      adjoining the D2 loop allowed binding of ssrA proteins but impaired their
      translocation. This loop, as in homologous nucleic-acid translocases, may bind
      substrates proximally and, coupled with ATP hydrolysis, translocate them
      distally, exerting mechanical force that mediates unfolding.

PMID- 15989954
TI  - Crystal structure of mitochondrial respiratory membrane protein complex II.
AB  - The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase
      (SQR) is an integral membrane protein complex in both the tricarboxylic acid
      cycle and aerobic respiration. Here we report the first crystal structure of
      Complex II from porcine heart at 2.4 A resolution and its complex structure with
      inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A
      resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein
      (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and
      CybS), as well as prosthetic groups required for electron transfer from succinate
      to ubiquinone. The structure correlates the protein environments around
      prosthetic groups with their unique midpoint redox potentials. Two ubiquinone
      binding sites are discussed and elucidated by TTFA binding. The Complex II
      structure provides a bona fide model for study of the mitochondrial respiratory
      system and human mitochondrial diseases related to mutations in this complex.

PMID- 15989955
TI  - A disulfide relay system in the intermembrane space of mitochondria that mediates
      protein import.
AB  - We describe here a pathway for the import of proteins into the intermembrane
      space (IMS) of mitochondria. Substrates of this pathway are proteins with
      conserved cysteine motifs, which are critical for import. After passage through
      the TOM channel, these proteins are covalently trapped by Mia40 via disulfide
      bridges. Mia40 contains cysteine residues, which are oxidized by the sulfhydryl
      oxidase Erv1. Depletion of Erv1 or conditions reducing Mia40 prevent protein
      import. We propose that Erv1 and Mia40 function as a disulfide relay system that
      catalyzes the import of proteins into the IMS by an oxidative folding mechanism.
      The existence of a disulfide exchange system in the IMS is unexpected in view of
      the free exchange of metabolites between IMS and cytosol via porin channels. We
      suggest that this process reflects the evolutionary origin of the IMS from the
      periplasmic space of the prokaryotic ancestors of mitochondria.

PMID- 15989956
TI  - ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor.
AB  - Although the importance of the ARF tumor suppressor in p53 regulation is well
      established, numerous studies indicate that ARF also suppresses cell growth in a
      p53/Mdm2-independent manner. To understand the mechanism of ARF-mediated tumor
      suppression, we identified a ubiquitin ligase, ARF-BP1, as a key factor
      associated with ARF in vivo. ARF-BP1 harbors a signature HECT motif, and its
      ubiquitin ligase activity is inhibited by ARF. Notably, inactivation of ARF-BP1,
      but not Mdm2, suppresses the growth of p53 null cells in a manner reminiscent of
      ARF induction. Surprisingly, in p53 wild-type cells, ARF-BP1 directly binds and
      ubiquitinates p53, and inactivation of endogenous ARF-BP1 is crucial for ARF
      mediated p53 stabilization. Thus, our study modifies the current view of ARF
      mediated p53 activation and reveals that ARF-BP1 is a critical mediator of both
      the p53-independent and p53-dependent tumor suppressor functions of ARF. As such,
      ARF-BP1 may serve as a potential target for therapeutic intervention in tumors
      regardless of p53 status.

PMID- 15989957
TI  - Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of
      Mcl-1 and regulates apoptosis.
AB  - The elimination of Mcl-1, an anti-apoptotic Bcl-2 family member, is an early and
      required step for DNA damage-induced apoptosis. The degradation of Mcl-1 can be
      blocked by proteasome inhibitors, suggesting a role for the ubiquitin proteasome
      pathway in apoptosis. Here, we demonstrate that Mcl-1 is ubiquinated at five
      lysines. Biochemical fractionation of cell extracts allowed us to identify a 482
      kDa HECT-domain-containing ubiquitin ligase named Mule (Mcl-1 ubiquitin ligase
      E3) that is both required and sufficient for the polyubiquitination of Mcl-1.
      Mule also contains a region similar to the Bcl-2 homology region 3 (BH3) domain
      that allows Mule to specifically interact with Mcl-1. Elimination of Mule
      expression by RNA interference stabilizes Mcl-1 protein, resulting in an
      attenuation of the apoptosis induced by DNA-damage agents. Thus, Mule is a unique
      BH3-containing E3 ubiquitin ligase apical to Bcl-2 family proteins during DNA
      damage-induced apoptosis.

PMID- 15989958
TI  - Antisense-mediated depletion reveals essential and specific functions of
      microRNAs in Drosophila development.
AB  - MicroRNAs are small noncoding RNAs that control gene function
      posttranscriptionally through mRNA degradation or translational inhibition. Much
      has been learned about the processing and mechanism of action of microRNAs, but
      little is known about their biological function. Here, we demonstrate that
      injection of 2'O-methyl antisense oligoribonucleotides into early Drosophila
      embryos leads to specific and efficient depletion of microRNAs and thus permits
      systematic loss-of-function analysis in vivo. Twenty-five of the forty-six
      embryonically expressed microRNAs show readily discernible defects; pleiotropy is
      moderate and family members display similar yet distinct phenotypes. Processes
      under microRNA regulation include cellularization and patterning in the
      blastoderm, morphogenesis, and cell survival. The largest microRNA family in
      Drosophila (miR-2/6/11/13/308) is required for suppressing embryonic apoptosis;
      this is achieved by differential posttranscriptional repression of the
      proapoptotic factors hid, grim, reaper, and sickle. Our findings demonstrate that
      microRNAs act as specific and essential regulators in a wide range of
      developmental processes.

PMID- 15989959
TI  - SLAM family receptors distinguish hematopoietic stem and progenitor cells and
      reveal endothelial niches for stem cells.
AB  - To improve our ability to identify hematopoietic stem cells (HSCs) and their
      localization in vivo, we compared the gene expression profiles of highly purified
      HSCs and non-self-renewing multipotent hematopoietic progenitors (MPPs). Cell
      surface receptors of the SLAM family, including CD150, CD244, and CD48, were
      differentially expressed among functionally distinct progenitors. HSCs were
      highly purified as CD150(+)CD244(-)CD48(-) cells while MPPs were CD244(+)CD150(
      )CD48(-) and most restricted progenitors were CD48(+)CD244(+)CD150(-). The
      primitiveness of hematopoietic progenitors could thus be predicted based on the
      combination of SLAM family members they expressed. This is the first family of
      receptors whose combinatorial expression precisely distinguishes stem and
      progenitor cells. The ability to purify HSCs based on a simple combination of
      SLAM receptors allowed us to identify HSCs in tissue sections. Many HSCs were
      associated with sinusoidal endothelium in spleen and bone marrow, though some
      HSCs were associated with endosteum. HSCs thus occupy multiple niches, including
      sinusoidal endothelium in diverse tissues.

PMID- 15989960
TI  - Regulation of apoptosis by alternative pre-mRNA splicing.
AB  - Apoptosis, a phenomenon that allows the regulated destruction and disposal of
      damaged or unwanted cells, is common to many cellular processes in multicellular
      organisms. In humans more than 200 proteins are involved in apoptosis, many of
      which are dysregulated or defective in human diseases including cancer. A large
      number of apoptotic factors are regulated via alternative splicing, a process
      that allows for the production of discrete protein isoforms with often distinct
      functions from a common mRNA precursor. The abundance of apoptosis genes that are
      alternatively spliced and the often antagonistic roles of the generated protein
      isoforms strongly imply that alternative splicing is a crucial mechanism for
      regulating life and death decisions. Importantly, modulation of isoform
      production of cell death proteins via pharmaceutical manipulation of alternative
      splicing may open up new therapeutic avenues for the treatment of disease.

PMID- 15989961
TI  - The TOR and EGO protein complexes orchestrate microautophagy in yeast.
AB  - The rapamycin-sensitive TOR signaling pathway in Saccharomyces cerevisiae
      positively controls cell growth in response to nutrient availability.
      Accordingly, TOR depletion or rapamycin treatment causes regulated entry of cells
      into a quiescent growth phase. Although this process has been elucidated in
      considerable detail, the transition from quiescence back to proliferation is
      poorly understood. Here, we describe the identification of a conserved member of
      the RagA subfamily of Ras-related GTPases, Gtr2, which acts in a vacuolar
      membrane-associated protein complex together with Ego1 and Ego3 to ensure proper
      exit from rapamycin-induced growth arrest. We demonstrate that the EGO complex,
      in conjunction with TOR, positively regulates microautophagy, thus
      counterbalancing the massive rapamycin-induced, macroautophagy-mediated membrane
      influx toward the vacuolar membrane. Moreover, large-scale genetic analyses of
      the EGO complex confirm the existence of a growth control mechanism originating
      at the vacuolar membrane and pinpoint the amino acid glutamine as a key
      metabolite in TOR signaling.

PMID- 15989962
TI  - Kinetics and thermodynamics make different contributions to RNA folding in vitro
      and in yeast.
AB  - RNAs somehow adopt specific functional structures despite the capacity to form
      alternative nonfunctional structures with similar stabilities. We analyzed RNA
      assembly during transcription in vitro and in yeast using hairpin ribozyme self
      cleavage to assess partitioning between functional ribozyme structures and
      nonfunctional stem loops. Complementary insertions located upstream of the
      ribozyme inhibited ribozyme assembly more than downstream insertions during
      transcription in vitro, consistent with a sequential folding model in which the
      outcome is determined by the structure that forms first. In contrast, both
      upstream and downstream insertions strongly inhibited assembly of the same
      ribozyme variants when expressed as chimeric mRNAs in yeast, indicating that
      inhibitory stem loops can form even after the entire ribozyme sequence has been
      transcribed. Evidently, some feature unique to the intracellular environment
      modulates the influence of transcription polarity and enhances the contribution
      of thermodynamic stability to RNA folding in vivo.

PMID- 15989963
TI  - Multiple RNA surveillance pathways limit aberrant expression of iron uptake mRNAs
      and prevent iron toxicity in S. cerevisiae.
AB  - Tight regulation of the expression of mRNAs encoding iron uptake proteins is
      essential to control iron homeostasis and avoid intracellular iron toxicity. We
      show that many mRNAs encoding iron uptake or iron mobilization proteins are
      expressed in iron-replete conditions in the absence of the S. cerevisiae RNase
      III ortholog Rnt1p or of the nuclear exosome component Rrp6p. Extended forms of
      these mRNAs accumulate in the absence of Rnt1p or of the 5'-->3' exonucleases
      Xrn1p and Rat1p, showing that multiple degradative pathways contribute to the
      surveillance of aberrant forms of these transcripts. RNase III-deficient cells
      are hypersensitive to high iron concentrations, suggesting that Rnt1p-mediated
      RNA surveillance is required to prevent iron toxicity. These results show that
      RNA surveillance through multiple ribonucleolytic pathways plays a role in iron
      homeostasis in yeast to avoid the potentially toxic effects of the expression of
      the iron starvation response in iron-replete conditions.

PMID- 15989964
TI  - Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires
      the cap binding complex.
AB  - Coupling between transcription and pre-mRNA splicing is a key regulatory
      mechanism in gene expression. Here, we investigate cotranscriptional spliceosome
      assembly in yeast, using in vivo crosslinking to determine the distribution of
      spliceosome components along intron-containing genes. Accumulation of the U1, U2,
      and U5 small nuclear ribonucleoprotein particles (snRNPs) and the 3' splice site
      binding factors Mud2p and BBP was detected in patterns indicative of progressive
      and complete spliceosome assembly; recruitment of the nineteen complex (NTC)
      component Prp19p suggests that splicing catalysis is also cotranscriptional. The
      separate dynamics of the U1, U2, and U5 snRNPs are consistent with stepwise
      recruitment of individual snRNPs rather than a preformed "penta-snRNP", as
      recently proposed. Finally, we show that the cap binding complex (CBC) is
      necessary, but not sufficient, for cotranscriptional spliceosome assembly. Thus,
      the demonstration of an essential link between CBC and spliceosome assembly in
      vivo indicates that 5' end capping couples pre-mRNA splicing to transcription.

PMID- 15989965
TI  - Cotranscriptional spliceosome assembly dynamics and the role of U1 snRNA:5'ss
      base pairing in yeast.
AB  - To investigate the mechanism of spliceosome assembly in vivo, we performed
      chromatin immunoprecipitation (ChIP) analysis of U1, U2, and U5 small nuclear
      ribonucleoprotein particles (snRNPs) to intron-containing yeast (S. cerevisiae)
      genes. The snRNPs display patterns that indicate a cotranscriptional assembly
      model: U1 first, then U2, and the U4/U6*U5 tri-snRNP followed by U1
      destabilization. cis-splicing mutations also support a role of U2 and/or the tri
      snRNP in U1 destabilization. Moreover, they indicate that splicing efficiency has
      a major impact on cotranscriptional snRNP recruitment and suggest that
      cotranscriptional recruitment of U2 or the tri-snRNP is required to commit the
      pre-mRNA to splicing. Branchpoint (BP) mutations had a major effect on the U1
      pattern, whereas 5' splice site (5'ss) mutations had a stronger effect on the U2
      pattern. A 5'ss-U1 snRNA complementation experiment suggests that pairing between
      U1 and the 5'ss occurs after U1 recruitment and contributes to a specific
      U1:substrate conformation required for efficient U2 and tri-snRNP recruitment.

PMID- 15989966
TI  - Genetic inactivation of the transcription factor TIF-IA leads to nucleolar
      disruption, cell cycle arrest, and p53-mediated apoptosis.
AB  - Growth-dependent regulation of rRNA synthesis is mediated by TIF-IA, a basal
      transcription initiation factor for RNA polymerase I. We inactivated the murine
      TIF-IA gene by homologous recombination in mice and embryonic fibroblasts (MEFs).
      TIF-IA-/- embryos die before or at embryonic day 9.5 (E9.5), displaying
      retardation of growth and development. In MEFs, Cre-mediated depletion of TIF-IA
      leads to disruption of nucleoli, cell cycle arrest, upregulation of p53, and
      induction of apoptosis. Elevated levels of p53 after TIF-IA depletion are due to
      increased binding of ribosomal proteins, such as L11, to MDM2 and decreased
      interaction of MDM2 with p53 and p19(ARF). RNAi-induced loss of p53 overcomes
      proliferation arrest and apoptosis in response to TIF-IA ablation. The striking
      correlation between perturbation of nucleolar function, elevated levels of p53,
      and induction of cell suicide supports the view that the nucleolus is a stress
      sensor that regulates p53 activity.

PMID- 15989967
TI  - MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in
      RNA polymerase II and is required for ER-mediated transcription.
AB  - Human TRAP/Mediator is a key coactivator for many transcription factors that act
      through direct interactions with distinct subunits, and MED1/TRAP220 is the main
      subunit target for various nuclear receptors. Remarkably, the current study shows
      that MED1/TRAP220 only exists in a TRAP/Mediator subpopulation (less then 20% of
      the total) that is greatly enriched in specific TRAP/Mediator subunits and is
      tightly associated with a near stoichiometeric level of RNA polymerase II.
      Importantly, this MED1/TRAP220-containing holoenzyme supports both basal- and
      activator-dependent transcription in an in vitro system lacking additional RNA
      polymerase II. Furthermore, chromatin immunoprecipitation experiments demonstrate
      an activator-selective recruitment of MED1/TRAP220-containing versus MED1/TRAP220
      deficient TRAP/Mediator complexes to estrogen receptor (ER) and p53 target genes,
      respectively. Finally, RNAi studies show that MED1/TRAP220 is required for ER
      mediated transcription and estrogen-dependent breast cancer cell growth. These
      observations have significant implications for our current understanding of the
      composition, heterogeneity, and functional specificity of TRAP/Mediator
      complexes.

PMID- 15989968
TI  - The role of the transcription bubble and TFIIB in promoter clearance by RNA
      polymerase II.
AB  - We have studied promoter clearance at a series of RNA polymerase II promoters
      with varying spacing of the TATA box and start site. We find that regardless of
      promoter spacing, the upstream edge of the transcription bubble forms 20 bp from
      TATA. The bubble expands downstream until 18 bases are unwound and the RNA is at
      least 7 nt long, at which point the upstream approximately 8 bases of the bubble
      abruptly reanneal (bubble collapse). If either bubble size or transcript length
      is insufficient, bubble collapse cannot occur. Bubble collapse coincides with the
      end of the requirement for the TFIIH helicase for efficient transcript
      elongation. We also provide evidence that bubble collapse suppresses pausing at
      +7 to +9 caused by the presence of the B finger segment of TFIIB within the
      complex. Our results indicate that bubble collapse defines the RNA polymerase II
      promoter clearance transition.

PMID- 15989969
TI  - Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase.
AB  - Viruses depend on host-derived factors for their efficient genome replication.
      Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase
      (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the
      hepatitis C virus (HCV) genome. CyPB interacted with the HCV RNA polymerase NS5B
      to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)
      mediated reduction of endogenous CyPB expression and the induced loss of NS5B
      binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as
      a stimulatory regulator of NS5B in HCV replication machinery. This regulation
      mechanism for viral replication identifies CyPB as a target for antiviral
      therapeutic strategies.

PMID- 15989970
TI  - Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the
      helicase Srs2p.
AB  - Posttranslational modification of proliferating cell nuclear antigen (PCNA), an
      essential processivity clamp for DNA polymerases, by ubiquitin and SUMO
      contributes to the coordination of DNA replication, damage tolerance, and
      mutagenesis. Whereas ubiquitination in response to DNA damage promotes the bypass
      of replication-blocking lesions, sumoylation during S phase is damage
      independent. As both modifiers target the same site on PCNA, an antagonistic
      action of SUMO on ubiquitin-dependent DNA damage tolerance has been proposed. We
      now present evidence that the apparent negative effect of SUMO on lesion bypass
      is not due to competition with ubiquitination but is rather mediated by the
      helicase Srs2p, which affects genome stability by suppressing unscheduled
      homologous recombination. We show that Srs2p physically interacts with sumoylated
      PCNA, which contributes to the recruitment of the helicase to replication forks.
      Our findings suggest a mechanism by which SUMO and ubiquitin cooperatively
      control the choice of pathway for the processing of DNA lesions during
      replication.

PMID- 15989971
TI  - Mutual inhibition of separase and Cdk1 by two-step complex formation.
AB  - Stable maintenance of genetic information requires chromosome segregation to
      occur with high accuracy. Anaphase is triggered when ring-shaped cohesin is
      cleaved by separase, a protease regulated by association with its inhibitor
      securin. Dispensability of vertebrate securin strongly suggests additional means
      of separase regulation. Indeed, sister chromatid separation but not securin
      degradation is inhibited by constitutively active cyclin-dependent kinase 1
      (Cdk1) and can be rescued solely by preventing phosphorylation of separase. We
      demonstrate that Cdk1-dependent phosphorylation of separase is not sufficient for
      inhibition. In a second step, Cdk1 stably binds phosphorylated separase via its
      regulatory cyclin B1 subunit. Complex formation results in inhibition of both
      protease and kinase, and we show that vertebrate separase is a direct inhibitor
      of Cdk1. This unanticipated function of separase is negatively regulated by
      securin but independent of separase's proteolytic activity.

PMID- 15989972
TI  - Diallyl sulfide inhibits diethylstilbesterol-induced DNA adducts in the breast of
      female ACI rats.
AB  - Diethylstilbestrol (DES) is metabolized to reactive intermediates that produce
      DNA adducts and ultimately cancer. Diallyl sulfide (DAS) has been shown to
      inhibit the metabolism of several procarcinogens. The ability of DES to produce
      DNA adducts in microsomal, mitochondrial, and nuclear in vitro metabolic systems
      and in the breast of female ACI rats, as well as ability of DAS to inhibit DNA
      adducts were investigated. Microsomes, mitochondria, and nuclei isolated from
      breast tissue of female ACI rats were used to catalyze oxidation reactions.
      Female ACI rats were treated i.p. as follows: (1) corn oil, (2) 200mg/kg DES, (3)
      200mg/kg DES/200mg/kg of DAS, (4) 200mg/kg DES/400mg/kg DAS. DES produced DNA
      adducts in each metabolic system. The relative adduct levels were 2.1 x 10(-4),
      6.2 x 10(-6), and 2.9 x 10(-7) in microsomal, mitochondrial, and nuclear
      reactions, respectively. DAS inhibited DNA adducts in each metabolic system. The
      percent inhibition ranged from 86% in microsomes to 93% in nuclei. DES produced
      DNA adducts in mtDNA and nDNA. DAS completely inhibited the DES-induced mtDNA
      adducts and caused a dose dependent decrease in nDNA adduct formation. These
      findings suggest that DAS could inhibit DES-induced breast cancer by inhibiting
      its metabolism.

PMID- 15989973
TI  - Long term dietary methoxychlor exposure in rats increases sodium solution
      consumption but has few effects on other sexually dimorphic behaviors.
AB  - Methoxychlor is an insecticide with estrogen-like activity, thus exposure during
      development might cause sexually dimorphic behavioral alterations. To evaluate
      this, pregnant rats consumed diets containing 0, 10, 100 or 1000 ppm methoxychlor
      from gestational day 7, and offspring continued on these diets until postnatal
      day (PND) 77. Assessments of sexually dimorphic behaviors in offspring indicated
      that intake of a 3.0% sodium chloride solution was significantly increased (41%)
      in males and females of the 1000 ppm group. No treatment group differed from
      controls in open field nor running wheel activity, play behavior, nor 0.3%
      saccharin solution intake. Offspring of the 1000 ppm group showed significantly
      decreased body weight, reaching 17% less than controls at PND 77, but not clearly
      related to their salt solution intake. During pregnancy, 1000 ppm dams consumed
      23% less food and weighed 10% less than controls, but this did not affect litter
      outcomes. These results indicate that in rodents, developmental and chronic
      exposure to dietary methoxychlor alters the sexually dimorphic behavior of salt
      solution intake in young adults of both sexes. Similar behavioral alterations
      with other xenoestrogens, and the potential for interactions among xenoestrogens,
      suggest that this report may minimize the true effects of dietary methoxychlor
      exposure.

PMID- 15989974
TI  - The role of c-Jun in the AP-1 activation induced by naturally occurring
      isothiocyanates.
AB  - Despite strong evidence that isothiocyanates (ITCs) inhibit cancer development,
      there are also reports that some of them induce or promote carcinogenesis. The
      molecular basis of the latter is largely unknown. We report here that all three
      ITCs that caused urinary bladder cancer in rats, including allyl ITC, benzyl ITC,
      and phenethyl ITC, increased the transactivation of activator protein 1 (AP-1)
      and AP-1 DNA binding in human bladder cancer UM-UC-3 cells. Amongst all Fos and
      Jun family members examined, only were the levels of c-Jun and Fra-2 consistently
      elevated by the ITCs. However, whereas c-Jun was identified as the predominant
      component in the AP-1 DNA binding complex, Fra-2 was not detected, suggesting
      that c-Jun may be mainly responsible for ITC-induced AP-1 activation. c-Jun was
      also induced by the ITCs in other bladder cancer cell lines (both human and rat)
      and by their N-acetylcysteine derivatives--their main urinary metabolites. c-Jun
      induction by the ITCs appears to involve both transcriptional activation and
      protein phosphorylation; the latter resulted from activation of c-Jun N-terminal
      kinase by the ITCs. Because c-Jun has been implicated in cancer development,
      including human bladder cancer, our data suggest that c-Jun activation may play
      an important role in ITC-induced bladder carcinogenesis.

PMID- 15989976
TI  - Checkpoint responses to replication fork barriers.
AB  - The fidelity of DNA replication is of paramount importance to the maintenance of
      genome integrity. When an active replication fork is perturbed, multiple cellular
      pathways are recruited to stabilize the replication apparatus and to help to
      bypass or correct the causative problem. However, if the problem is not
      corrected, the fork may collapse, exposing free DNA ends to potentially
      inappropriate processing. In prokaryotes, replication fork collapse promotes the
      activity of recombination proteins to restore a replication fork. Recent work has
      demonstrated that recombination is also intimately linked to replication in
      eukaryotic cells, and that recombination proteins are recruited to collapsed, but
      not stalled, replication forks. In this review we discuss the different types of
      potential replication fork barriers (RFB) and how these distinct RFBs can result
      in different DNA structures at the stalled replication fork. The DNA structure
      checkpoints which act within S phase respond to different RFBs in different ways
      and we thus discuss the processes that are controlled by the DNA replication
      checkpoints, paying particular attention to the function of the intra-S phase
      checkpoint that stabilises the stalled fork.

PMID- 15989975
TI  - Localization of checkpoint and repair proteins in eukaryotes.
AB  - In eukaryotes, the cellular response to DNA damage depends on the type of DNA
      structure being recognized by the checkpoint and repair machinery. DNA ends and
      single-stranded DNA are hallmarks of double-strand breaks and replication stress.
      These two structures are recognized by distinct sets of proteins, which are
      reorganized into a focal assembly at the lesion. Moreover, the composition of
      these foci is coordinated with cell cycle progression, reflecting the favoring of
      end-joining in the G1 phase and homologous recombination in S and G2. The
      assembly of proteins at sites of DNA damage is largely controlled by a network of
      protein-protein interactions, with the Mre11 complex initiating assembly at DNA
      ends and replication protein A directing recruitment to single-stranded DNA. This
      review summarizes current knowledge on the cellular organization of DSB repair
      and checkpoint proteins focusing on budding yeast and mammalian cells.

PMID- 15989977
TI  - Tails and cuts: the role of histone post-translational modifications in the
      formation of programmed double-strand breaks.
AB  - In eukaryotic organisms, various DNA recombination mechanisms have been described
      that are an integral part of nuclear differentiation processes. In several
      places, the recombination is initiated by one or more double-strand breaks that
      result from the action of specific endonucleolytic activities. The importance of
      chromatin in controlling susceptibility of DNA to various DNA transactions has
      been recognized for long. Recent literature links post-transcriptional
      modifications of the amino-terminal part of histones (the tails) to the formation
      of developmentally regulated DNA double-strand break (the cuts). In this review,
      I compare the existing data in three different DNA rearrangement-based processes,
      i.e., genetic recombination associated to meiosis, lymphoid-specific V(D)J
      recombination and excision of DNA fragments in the nucleus of ciliates. Inspired
      by some of the concepts established in the field of transcription, models are
      proposed for molecular mechanisms that sustain the epigenetic control of
      programmed double-strand break formation.

PMID- 15989978
TI  - Telomeres and DNA damage checkpoints.
AB  - In all eukaryotic organisms, interruptions in duplex DNA molecules elicit a DNA
      damage response, which includes activation of DNA repair machineries and
      surveillance mechanisms, known as DNA damage checkpoints. Telomeres and double
      strand breaks (DSBs) share the common feature of being physical ends of
      chromosomes. However, unlike DSBs, telomeres do not activate the DNA damage
      checkpoints and are usually protected from end-to-end fusions and other
      processing events that normally promote repair of DNA breaks. This indicates that
      they are shielded from being recognized and processed as DSBs. On the other hand,
      chromosome ends resemble damaged DNA, as several factors required for DNA repair
      and checkpoint networks play important roles in telomere length maintenance. Due
      to the critical role of both DNA damage checkpoints and telomere homeostasis in
      maintaining genetic stability and in counteracting cancer development, the
      knowledge of their interconnections is essential for our understanding of these
      key cellular controls.

PMID- 15989979
TI  - Regulation of histone synthesis and nucleosome assembly.
AB  - Histone deposition onto nascent DNA is the first step in the process of chromatin
      assembly during DNA replication. The process of nucleosome assembly represents a
      daunting task for S-phase cells, partly because cells need to rapidly package
      nascent DNA into nucleosomes while avoiding the generation of excess histones.
      Consequently, cells have evolved a number of nucleosome assembly factors and
      regulatory mechanisms that collectively function to coordinate the rates of
      histone and DNA synthesis during both normal cell cycle progression and in
      response to conditions that interfere with DNA replication.

PMID- 15989980
TI  - Adaptation to DNA damage and stimulation of genetic instability: the double-edged
      sword mammalian DNA polymerase kappa.
AB  - A major tolerance mechanism that functions to replicate damaged genomic DNA
      across lesions that have escaped elimination by repair mechanism is translesion
      DNA synthesis (TLS). DNA polymerase kappa (Pol kappa), a specialised low-fidelity
      DNA polymerase which is able to perform DNA synthesis across several damaged
      bases, is one of the enzymes involved in the process. The mutagenic nature of Pol
      kappa implies that its expression must be tightly regulated to prevent the
      formation of excessive genetic disorders along undamaged parts of the genome.
      Indeed, Pol kappa overexpression, which is notably observed in lung cancer,
      results not only in increased spontaneous mutagenesis, but also in pleiotropic
      alterations such as DNA breaks, genetic exchanges and aneuploidy. This review
      will discuss both aspects of DNA polymerase kappa, which can be considered as a
      genomic supervisor participating in genome maintenance and when misregulated as a
      genetic instability enhancer as well.

PMID- 15989982
TI  - Comparison of the maternal and neonatal effects of epidural block and of combined
      spinal-epidural block for Cesarean section.
AB  - BACKGROUND: Combined spinal-epidural block (CSEB) has aroused increasing
      interest, as it combines the reliability of a spinal block and the flexibility of
      an epidural block (EB). We have conducted a comparative investigation of the
      maternal and fetal effects of CSEB and of EB administered for Cesarean section.
      METHODS: Eighty pregnant women at term were randomized into two groups. Women in
      the CSEB group (N = 40) were each given 1.5-1.8 mL 0.5% hyperbaric bupivacaine
      intrathecally, followed by 10 mL 0.25% bupivacaine and 50 microg fentanyl through
      the epidural catheter 10 min later. Women in the EB group (N = 40) received 14-16
      mL 0.5% bupivacaine and 100 microg fentanyl. The quality and side effects of
      surgical anesthesia and the hemodynamic parameters, Apgar scores, and
      postoperative duration of pain were compared between the two groups. RESULTS: The
      time for the block to reach the T-4 level differed significantly between the two
      groups (8.02 +/- 3.4 versus 18.34 +/- 4.6; P < 0.01). More women in the CSEB
      group achieved complete motor blockade (Bromage score 3), and it was reached
      earlier than in the EB group (P < 0.05). Muscle relaxation and motor block were
      better in the CSEB group than in the EB group (P < 0.01). Apgar scores were 7 or
      more in almost all newborns in both groups. There were no significant differences
      between the groups in the incidences of adverse effects such as hypotension or
      nausea and vomiting, but the patients in the EB group experienced more shivering
      (P < 0.001). The time to postoperative pain was significantly shorter in the CSEB
      group. CONCLUSION: We decided that CSEB, and more specifically spinal anesthesia
      with supporting epidural anesthesia, has greater efficacy and fewer side effects
      than EB when administered for Cesarean section.

PMID- 15989983
TI  - 50gram oral glucose challenge test combined with risk factor-based screening for
      gestational diabetes.
AB  - OBJECTIVE: Our aim was to study whether universal screening of all pregnant women
      by Oral Glucose Challenge Test (OGCT) would identify a higher number of women
      with Gestational Diabetes (GDM) than risk factor based screening. STUDY DESIGN: A
      50 g OGCT test was performed prospectively in 532 unselected women at 26-28 weeks
      of gestation. The 1-h venous plasma glucose concentration of >7.3 mmol/l was
      considered as a positive screening result. Patients with a positive OGCT
      underwent a 75 g 2-h OGTT, which was used as the actual diagnostic test for GDM.
      When two or all three of the glucose concentrations in OGTT (measured at fasting
      state and 1 and 2 h after the 75 g glucose load) were above the 97.5th percentile
      the patient was considered as having GDM. In addition, women with risk factors
      for GDM also underwent a 75 g OGTT regardless of the result of the OGCT. RESULTS:
      A positive 50 g OGCT was obtained in 123 (23%) of the women. In 15 (12%) of
      these, a diagnosis of GDM was established by the subsequent OGTT. Out of the 409
      remaining women with a normal OGCT, 148 (36%) had risk factors for GDM. An OGTT
      performed in these patients identified 4 additional women with a GDM. Seventy
      nine percent of GDM was thus found with 50g OGCT without regarding risk factors.
      Forty-seven percent of the women with GDM would have been missed in screening by
      risk factors only. CONCLUSIONS: In our population 50 g OGCT appears to identify a
      higher number of GDM than risk factor based screening. Combined with risk factor
      screening a few more cases of GDM would be found.

PMID- 15989984
TI  - Oral glucose tolerance testing at gestational weeks < or =16 could predict or
      exclude subsequent gestational diabetes mellitus during the current pregnancy in
      high risk group.
AB  - BACKGROUND: An oral glucose tolerance test with a result that is negative but
      close to the diagnostic cut-off in early pregnancy was hypothesized to serve as a
      predictor of subsequent gestational diabetes in a high risk group. The aim of the
      study was to determine those cut-off values of OGTT at gestational weeks < or
      =16, which can predict or exclude subsequent onset of GDM in a high risk group.
      METHODS: Pregnant women at high risk of gestational diabetes (n = 163) underwent
      a 2-h, 75-g oral glucose tolerance test at gestational weeks < or =16 were
      analyzed in this study. In the event of a negative result, subsequent oral
      glucose tolerance tests were performed at gestational weeks 24-28 and 32-34. The
      sensitivity, the specificity, the positive and negative predictive values and the
      Odds ratio of the best cut-off values of fasting and postload glucose levels were
      calculated. RESULTS: The best cut-off values to exclude subsequent GDM for
      fasting and postload glucose were 5.0 and 6.2 mmol/l, respectively. In
      combination, the best cut-off values were 5.3 mmol/l for fasting and 6.8 mmol/l
      for postload glucose, with negative predictive values of 0.97 and 0.71 and
      sensitivities of 96.9 and 86.3 at gestational weeks 24-28 and 32-34,
      respectively. Combination of these cut-off values with obesity proved to be very
      predictive for gestational diabetes by gestational weeks 32-34, with an Odds
      ratio of 6.0 [95% confidence interval: 1.7-21.0]. CONCLUSIONS: With regard to the
      very high negative predictive value of the method, pregnant women with glucose
      levels of < or =5.3 mmol/l at fasting and of < or = 6.8 mmol/l at postload in
      gestational weeks < or =16 should undergo subsequent oral glucose tolerance
      testing merely at gestational weeks 32-34. Approximately a quarter (24.5%) of the
      pregnant women at risk of gestational diabetes satisfied these criteria.

PMID- 15989985
TI  - Comparison of in vitro fertilization outcome in women with and without
      sonographic evidence of polycystic ovarian morphology.
AB  - OBJECTIVE: This study compared the outcome of in vitro fertilization (IVF)
      treatment in women who had polycystic ovaries (PCO) seen on an ultrasound scan,
      but who had no clinical symptomatology associated with polycystic ovary syndrome,
      with that of women who had normal ovarian morphology on ultrasound examination.
      METHODS: Outcome of IVF 39 women with PCO evidence by ultrasound compared with
      102 women, who had normal ovarian morphology by ultrasound. All 141 women had
      normal early follicular phase serum follicle stimulating hormone (FSH)
      concentration, were less than 40 years of age and used the long protocol
      pituitary suppression with gonadotropin-releasing hormone agonist therapy.
      RESULTS: On average, the women with PCO produced more follicles and oocytes than
      the women with normal ovaries, but the fertilization cleavage and pregnancy rates
      were similar. CONCLUSION: Although the response to follicular stimulation in PCO
      women is better than that for women with normal ovaries, the outcome of pregnancy
      in vitro fertilization is similar.

PMID- 15989986
TI  - Expression of nectin-2 in mouse granulosa cells.
AB  - OBJECTIVE: The development and maturation of the ovarian follicles are
      characterized by structural changes that require components involved in cell-cell
      adhesion systems. Recently a novel group of cell adhesion molecules named nectins
      has been identified. The present study examined expression and cell-specific
      localization of nectins during mouse follicular development. STUDY DESIGN:
      Expression of nectins in mouse ovary was investigated by immnuoblot analysis and
      immunohistochemistry. More precise localization was determined by electron
      microscopy. RESULTS: Immunoblot analysis revealed expression of nectin-2 and
      nectin-3 but not nectin-1 in ovarian granulosa cells. Immunohistochemistry
      demonstrated expression of nectin-2 at cell-cell adhesion sites of granulosa cell
      layer in the primary and preantral follicles. Especially, intense
      immunoreactivity of nectin-2 accumulated around the zona pellucida. In antral
      follicles, the intensity of nectin-2 expression on granulosa cells was decreased.
      By electron microscopy nectin-2 was detected not only on thin extensions of
      granulosa cells penetrating the zona pellucida, but also on the attachment sites
      between thin extensions of granulosa cells and oocyte surface. CONCLUSION: The
      restricted expression of nectin-2 in the granulosa cells of primary and preantral
      follicles might reflect some of the molecular changes in cell-cell adhesion
      during early follicular development.

PMID- 15989987
TI  - Small doses of LH activity are needed early in ovarian stimulation for better
      quality oocytes in IVF-ET.
AB  - OBJECTIVE: To examine whether exogenous LH administration has a beneficial effect
      on the quality of oocytes, fertilization potential, as well as pregnancy rate in
      IVF-ET cycles. A randomized trial comparing r-FSH versus r-FSH and LH was
      employed. STUDY DESIGN: Forty-six infertile couples entering IVF-ET for the first
      time (either tubal or male factor) were divided after prospective randomization
      into two groups. In both groups the long protocol with GnRH-analogs was used. In
      group A, ovarian stimulation started with r-FSH (200 IU/day) for the first four
      days. In group B, the stimulation protocol started with one amp hMG (75 IU FSH +
      75 IU LH activity) daily for four days, with simultaneous administration of r-FSH
      (150 IU/day). The outcome was compared. RESULTS: Statistical difference was
      observed in the number of mature oocytes, the number of fertilized oocytes as
      well as the number of transferable embryos. In all cases, results were
      statistically significantly better (p < 0.05) in group B. Clinical pregnancy
      rate, finally, was similar in the two groups. CONCLUSION: The relatively small
      sample size does not allow a definitive conclusion for the important role of LH
      during early oocyte maturation. Our results, however, indicate a beneficial
      effect when small doses of LH are used for ovarian stimulation in IVF-ET cycles.
      This effect may be more important in cases in which few embryos are available for
      transfer.

PMID- 15989988
TI  - Bartter's syndrome and pregnancy.

PMID- 15989989
TI  - Combination therapy for a pregnant woman with severe refractory ITP.

PMID- 15989990
TI  - Hemolysis, elevated liver enzymes, and low platelets syndrome, peripartal
      cardiomyopathy and disseminated intravascular coagulation during the puerperium.

PMID- 15989991
TI  - Specialist life--Dr Ernest Ng.

PMID- 15989992
TI  - Commentary on increased risk of biochemical and local failure in patients with a
      distended rectum on the planning CT for prostate cancer radiotherapy.

PMID- 15989993
TI  - The cell's-eye view: assessing dose in four dimensions.

PMID- 15989994
TI  - Consultation chaos.

PMID- 15989995
TI  - Health-related quality of life in men receiving prostate brachytherapy on RTOG 98
      05.
AB  - PURPOSE: To prospectively assess health-related quality of life (HRQOL) during
      the first year after treatment with prostate brachytherapy (PB) alone for T1c-2a
      prostate cancer. MATERIALS AND METHODS: Ninety-eight patients from 24
      institutions were eligible and properly entered on this study. All patients were
      treated with PB alone using I-125 (Oncura Model 6711). The prescription dose was
      145 Gy. Three separate health-related quality of life questionnaires (HRQOL)
      (Functional Assessment of Cancer Therapy-Prostate [FACT-P], Sexual Adjustment
      Questionnaire [SAQ], and International Prostate Symptom Score [IPSS]) were self
      administered before and after PB (baseline; 3, 6, 9, and 12 months after PB). The
      standard error of the mean (SEM) was used to analyze changes in HRQOL scores over
      time. Patients who improved greater than the SEM were categorized as improved;
      patients that declined greater than the SEM were categorized as declined;
      patients were otherwise categorized as stable. All changes are measured using the
      pretreatment HRQOL score as baseline. RESULTS: The percentage of men who reported
      the ability to have an erection decreased from 73% at baseline (65% unassisted,
      8% assisted) to 57% at 1 year (36% unassisted, 21% assisted). The rate of urinary
      incontinence increased to 14% at 6 months but had decreased to 1% at the 12-month
      follow-up. At 1 year after PB, 80% of men reported decreased sexual functioning
      according to SAQ scores. More than 60% of men reported decreased urinary function
      at 12 months compared with baseline. CONCLUSIONS: This article represents the
      first prospective, multi-institutional study of HRQOL in men treated with PB and
      demonstrates that patients undergoing PB have a very high overall HRQOL. The rate
      of incontinence by 1 year after PB is low, but many patients continue to have
      obstructive symptoms at 1 year. Although 78% of 1-year respondents state that
      they can achieve an erection with or without assistance, almost 50% report a
      decrease in sexual function.

PMID- 15989996
TI  - Increased risk of biochemical and local failure in patients with distended rectum
      on the planning CT for prostate cancer radiotherapy.
AB  - PURPOSE: To retrospectively test the hypothesis that rectal distension on the
      planning computed tomography (CT) scan is associated with an increased risk of
      biochemical and local failure among patients irradiated for prostate carcinoma
      when a daily repositioning technique based on direct prostate-organ localization
      is not used. METHODS AND MATERIALS: This study included 127 patients who received
      definitive three-dimensional conformal radiotherapy for prostate cancer to a
      total dose of 78 Gy at The University of Texas M. D. Anderson Cancer Center.
      Rectal distension was assessed by calculation of the average cross-sectional
      rectal area (CSA; defined as the rectal volume divided by length) and measuring
      three rectal diameters on the planning CT. The impact of rectal distension on
      biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or
      greater late rectal bleeding was assessed. RESULTS: The incidence of biochemical
      failure was significantly higher among patients with distended rectums (CSA >11.2
      cm(2)) on the planning CT scan (p = 0.0009, log-rank test). Multivariate analysis
      indicates that rectal distension and high-risk disease are independent risk
      factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to
      9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The
      probability of residual tumor without evidence of radiation treatment (as scored
      by the pathologist) increased significantly with rectal distension (p = 0.010,
      logistic analysis), and a lower incidence of Grade 2 or greater late rectal
      bleeding within 2 years was simultaneously observed with higher CSA values (p =
      0.031, logistic analysis). CONCLUSIONS: We found strong evidence that rectal
      distension on the treatment-planning CT scan decreased the probability of
      biochemical control, local control, and rectal toxicity in patients who were
      treated without daily image-guided prostate localization, presumably because of
      geographic misses. Therefore, an empty rectum is warranted at the time of
      simulation. These results also emphasize the need for image-guided radiotherapy
      to improve local control in irradiating prostate cancer.

PMID- 15989997
TI  - Sequential evaluation of prostate edema after permanent seed prostate
      brachytherapy using CT-MRI fusion.
AB  - PURPOSE: To analyze the extent and time course of prostate edema and its effect
      on dosimetry after permanent seed prostate brachytherapy. METHODS AND MATERIALS:
      Twenty patients scheduled for permanent seed (125)I prostate brachytherapy agreed
      to a prospective study on postimplant edema. Implants were preplanned using
      transrectal ultrasonography. Postimplant dosimetry was calculated using computed
      tomography-magnetic resonance imaging (CT-MRI) fusion on the day of the implant
      (Day 1) and Days 8 and 30. The prostate was contoured on MRI, and the seeds were
      located on CT. Factors investigated for an influence on edema were the number of
      seeds and needles, preimplant prostate volume, transitional zone index
      (transition zone volume divided by prostate volume), age, and prostate-specific
      antigen level. Prostate dosimetry was evaluated by the percentage of the prostate
      volume receiving 100% of the prescribed dose (V(100)) and percentage of
      prescribed dose received by 90% of the prostate volume (D(90)). RESULTS: Prostate
      edema was maximal on Day 1, with the median prostate volume 31% greater than
      preimplant transrectal ultrasound volume (range, 0.93-1.72; p < 0.001) and
      decreased with time. It was 21% greater than baseline at Day 8 (p = 0.013) and 5%
      greater on Day 30 (p < 0.001). Three patients still had a prostate volume greater
      than baseline by Day 30. The extent of edema depended on the transition zone
      volume (p = 0.016) and the preplan prostate volume (p = 0.003). The median V(100)
      on Day 1 was 93.6% (range, 86.0-98.2%) and was 96.3% (range, 85.7-99.5%) on Day
      30 (p = 0.079). Patients with a Day 1 V(100) >93% were less affected by edema
      resolution, showing a median increase in V(100) of 0.67% on Day 30 compared with
      2.77% for patients with a V(100) <93 % on Day 1. CONCLUSION: Despite the extreme
      range of postimplant edema, the effect on dosimetry was less than expected. Dose
      coverage of the prostate was good for all patients during Days 1-30. Our data
      indicate that postimplant dosimetry on the day of implant is sufficient for
      patients with good dose coverage (Day 1 V(100) >93%).

PMID- 15989998
TI  - Detailed urethral dosimetry in the evaluation of prostate brachytherapy-related
      urinary morbidity.
AB  - PURPOSE: To evaluate the relationship between urinary morbidity after prostate
      brachytherapy and urethral doses calculated at the base, midprostate, apex, and
      urogenital diaphragm. METHODS AND MATERIALS: From February 1998 through July
      2002, 186 consecutive patients without a prior history of a transurethral
      resection underwent monotherapeutic brachytherapy (no supplemental external beam
      radiation therapy or androgen deprivation therapy) with urethral-sparing
      techniques (average urethral dose 100%-140% minimum peripheral dose) for clinical
      T1c-T2b (2002 AJCC) prostate cancer. The median follow-up was 45.5 months.
      Urinary morbidity was defined by time to International Prostate Symptom Score
      (IPSS) resolution, maximum increase in IPSS, catheter dependency, and the need
      for postimplant surgical intervention. An alpha blocker was initiated
      approximately 2 weeks before implantation and continued at least until the IPSS
      returned to baseline. Evaluated parameters included overall urethral dose
      (average and maximum), doses to the base, midprostate, apex, and urogenital
      diaphragm, patient age, clinical T stage, preimplant IPSS, ultrasound volume,
      isotope, and D90 and V100/150/200. RESULTS: Of the 186 patients, 176 (94.6%) had
      the urinary catheter permanently removed on the day of implantation with only 1
      patient requiring a urinary catheter >5 days. No patient had a urethral stricture
      and only 2 patients (1.1%) required a postbrachytherapy transurethral resection
      of the prostate (TURP). For the entire cohort, IPSS on average peaked 2 weeks
      after implantation with a mean and median time to IPSS resolution of 14 and 3
      weeks, respectively. For the entire cohort, only isotope predicted for IPSS
      resolution, while neither overall average prostatic urethra nor segmental
      urethral dose predicted for IPSS resolution. The maximum postimplant IPSS
      increase was best predicted by preimplant IPSS and the maximum apical urethral
      dose. CONCLUSIONS: With the routine use of prophylactic alpha blockers and strict
      adherence to urethral-sparing techniques, detailed urethral dosimetry did not
      substantially improve the ability to predict urinary morbidity. Neither the
      average dose to the prostatic urethra nor urethral doses stratified into base,
      midprostate, apex, or urogenital diaphragm segments predicted for IPSS
      normalization. Radiation doses of 100%-140% minimum peripheral dose are well
      tolerated by all segments of the prostatic urethra with resultant tumoricidal
      doses to foci of periurethral cancer.

PMID- 15990000
TI  - Dose-volumetric parameters of acute esophageal toxicity in patients with lung
      cancer treated with three-dimensional conformal radiotherapy.
AB  - PURPOSE: To retrospectively evaluate which dose-volumetric parameters are
      associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in
      lung cancer patients treated with three-dimensional conformal radiotherapy (3D
      CRT). METHODS AND MATERIALS: One hundred twenty-four lung cancer patients treated
      curatively with 3D-CRT were retrospectively analyzed. All patients received
      conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range,
      54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients
      underwent curative surgery before RT. Ninety-two patients received chemotherapy
      (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was
      scored by Radiation Therapy Oncology Group criteria. The parameters analyzed
      included sex; age; Karnofsky performance score; weight loss; surgery; concurrent
      chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or
      =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58
      Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute
      length of the esophagus irradiated; the maximum and mean dose to the esophagus;
      and normal tissue complication probability. RESULTS: Of the 124 patients, 15
      patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was
      no fatal Grade 5 AET. In univariate and multivariate logistic regression
      analyses, concurrent chemotherapy and V60 were significantly associated with the
      development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in
      15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50
      patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87
      patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 >
      30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy,
      severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of
      7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received
      concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with
      V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037).
      CONCLUSIONS: Concurrent chemotherapy and V60 were associated with the development
      of severe AET > or = Grade 3. For patients being treated with concurrent
      chemotherapy, V60 is considered to be a useful parameter predicting the risk of
      severe AET after conventionally fractionated 3D-CRT for lung cancer.

PMID- 15989999
TI  - Selective mediastinal node irradiation based on FDG-PET scan data in patients
      with non-small-cell lung cancer: a prospective clinical study.
AB  - PURPOSE: To evaluate the patterns of recurrence when selective mediastinal node
      irradiation based on FDG-PET scan data is used in patients with non-small-cell
      lung cancer (NSCLC). METHODS AND MATERIALS: A prospective Phase I/II study was
      undertaken on 44 patients with NSCLC without detectable distant metastases on CT
      and FDG-PET scan, delivering either 61.2 Gy in 34 fractions over 23 days or 64.8
      Gy in 36 fractions over 24 days (1.8 Gy b.i.d. with 8-h interval). Only the
      primary tumor and the positive mediastinal areas on the pretreatment FDG-PET scan
      were irradiated. Isolated nodal failure was defined as recurrence in the regional
      nodes outside of the clinical target volume, in the absence of in-field failure.
      RESULTS: The CT and FDG-PET stage distribution was as follows: Stage I: 8
      patients (18%) and 13 patients (29%); Stage II: 6 patients (14%) and 10 patients
      (23%); Stage IIIA: 15 patients (34%) and 7 patients (16%); Stage IIIB: 15
      patients (34%) and 14 patients (32%), respectively. After a median follow-up time
      of 16 months (95% confidence interval [CI], 11-21 months) postradiotherapy, 11
      patients (25%) developed a local recurrence. Only 1 patient (crude rate, 2.3%;
      upper bound of 95% CI, 10.3%), with a Stage II tumor on both CT and PET,
      developed an isolated nodal failure. The median actuarial overall survival was 21
      months (95% CI, 14-28 months), and the median actuarial progression-free survival
      was 18 months (95% CI, 12-24 months). CONCLUSIONS: Selective mediastinal node
      irradiation based on FDG-PET scan data in patients with NSCLC results in low
      isolated nodal failure rates. In the Phase I component of this trial, radiation
      dose escalation up to 64.8 Gy in 36 fractions over 24 days is feasible.

PMID- 15990001
TI  - Differences in pulmonary function before vs. 1 year after hypofractionated
      stereotactic radiotherapy for small peripheral lung tumors.
AB  - PURPOSE: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy
      (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small
      peripheral lung tumors. METHODS AND MATERIALS: A total of 17 lesions in 15
      patients with small peripheral lung tumors, who underwent SRT between February
      2000 and April 2003, were included in this study. Twelve patients had primary
      lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was
      T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number
      of cigarettes smoked per day multiplied by number of years of smoking).
      Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8
      fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test
      parameters included total lung capacity (TLC), vital capacity (VC), forced
      expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon
      monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment
      related factors, including age, the Brinkman index, internal target volume, the
      percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25,
      and V30, respectively), and mean lung dose. RESULTS: There were no significant
      changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from
      baseline in DLCO was significantly increased by 128.2%. Univariate and
      multivariate analyses revealed a correlation between DLCO and the Brinkman index.
      CONCLUSIONS: One year after SRT as compared with before SRT, there were no
      declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy
      smokers before SRT, suggesting a correlation between DLCO and smoking cessation.
      SRT seems to be tolerable in view of long-term lung function.

PMID- 15990002
TI  - Preliminary report of the 6-minute walk test as a predictor of radiation-induced
      pulmonary toxicity.
AB  - PURPOSE: To assess the 6-minute walk test (6MWT) as a predictor of radiation
      therapy-induced lung injury (RTLI). METHODS AND MATERIALS: The 6MWT is a simple,
      economical, and reproducible test that measures both how far a person can walk in
      6 min and any associated changes in vital signs. As part of a prospective trial
      to study RTLI, a pre-RT 6MWT was performed in 41 patients. The predictive
      capacities of pre-RT 6MWT, forced expiratory volume in 1 s (FEV1), and single
      breath diffusing capacity for carbon monoxide (DLCO) for the development of RTLI
      were assessed with receiver operating curve (ROC) techniques. To evaluate the
      6MWT, alone or with mean lung dose (MLD) of radiation, as a predictor of RTLI,
      the rates of RTLI in patient subgroups defined by 6MWT results were compared by
      using Fisher's exact test. RESULTS: Thirty-one patients with > or =3 months'
      follow-up were evaluable. The median baseline 6MWT result was 1400 ft. Of 31
      patients, 7 developed Grade > or =2 RTLI. Of 15 patients with an MLD >18 Gy (the
      median), 5 developed RTLI, compared with 2 of 16 with MLD < or =18 Gy (p = 0.22).
      Among those with an MLD < or =18 Gy, the RTLI rates were 0 of 8 and 2 of 8 for
      6MWT results > or =1400 ft or <1400 ft, respectively, p = 0.46. The ROC area
      under the curve for individual metrics was as follows: FEV1 0.66, MLD 0.70, DLCO
      0.61, and 6MWT 0.47. Combining FEV1 with 6MWT increased the ROC to 0.71,
      suggesting that the ratio might be a better predictor than the individual values.
      Patients with a high 6MWT/FEV1 ratio had a lower rate of RTLI than those with a
      relatively low ratio. CONCLUSIONS: The 6MWT might provide prognostic information
      beyond pulmonary function tests and dosimetric parameters in predicting RTLI.
      Additional work is needed to better assess the utility of these functional
      metrics.

PMID- 15990003
TI  - Late course accelerated hyperfractionated radiotherapy plus concurrent
      chemotherapy for squamous cell carcinoma of the esophagus: a phase III randomized
      study.
AB  - PURPOSE: Late course accelerated hyperfractionated (LCAF) radiotherapy (RT) is as
      effective as standard chemoradiotherapy for nonsurgical management of locally
      advanced esophageal squamous cell carcinoma (SCC). We have evaluated further the
      efficacy of concurrent LCAF RT and chemotherapy. METHODS AND MATERIALS: In all,
      111 eligible patients with esophageal SCC were randomized to receive LCAF alone
      (LCAF) or concurrent LCAF and chemotherapy (LCAT+CT) between March 1998 and July
      2000. All patients received conventional fractionation irradiation of 1.8 Gy per
      day, to a dose of 41.4 Gy/23 fractions in 4-5 weeks, followed by accelerated
      hyperfractionated irradiation using reduced fields, 1.5 Gy/fractions twice a day,
      to a dose of 27 Gy in 18 days. Thus, the total dose was 68.4 Gy/41 fractions in
      44 days. Fifty-four patients in the LCAF+CT arm had an additional four cycles of
      chemotherapy using cisplatin 25 mg/m(2) daily and fluorouracil (5-FU) 600 mg/m(2)
      daily on Days 1-3 every 4 weeks starting on the same day that LCAF was delivered.
      RESULTS: The median survival was 23.9 months (95% confidence [CI], 20.1-27.7) for
      the LCAF arm and 30.8 months (95% CI, 17.6-44.1) for the LCAF+CT arm,
      respectively. Survival rates at 1, 3, and 5 years of the LCAF arm were 77%, 39%,
      and 28%, respectively, while those of the LCAF+CT arm were 67%, 44%, and 40%,
      respectively (p = 0.310). Grades 3 and 4 acute toxicities occurred in 46% and 25%
      of the patients in the LCAF arm and the LCAF+CT arm, respectively; 6% of the
      patients in the combined arm had Grade 5 acute toxicities, whereas none was noted
      in the LCAF alone arm. CONCLUSIONS: Late course accelerated hyperfractionation
      was effective for locally advanced esophageal SCC. There was a trend toward
      better survival among patients who received intensified treatment with concurrent
      chemotherapy. Further randomized studies with a larger number of patients should
      be carried out, but additional measures must be taken to reduce the higher
      mortality rate due to chemotherapy-related acute toxicities.

PMID- 15990004
TI  - Definition of elective lymphatic target volume in ductal carcinoma of the
      pancreatic head based on histopathologic analysis.
AB  - PURPOSE: In chemoradiation for pancreatic carcinoma three-dimensional target
      volume definitions could maximize tolerability and therapeutic effect at the same
      time because toxicity correlates with treatment volume. We aimed to define
      guidelines for elective treatment of nodal areas based on pathologic nodal
      involvement to optimize treatment volume for this tumor. METHODS AND MATERIALS:
      Pathologic patterns of regional nodal spread in 175 patients who underwent
      primary pancreatoduodenectomy with > or =10 assessed nodes and literature data on
      para-aortic spread were the base of the definition of the target volume.
      Significant correlations between spread to lymphatic areas and tumor
      characteristics were determined using Fisher's exact test. Computed tomography
      scans and a Pinnacle3 (Philips, Best, The Netherlands) system were used for
      treatment planning. RESULTS: Among 175 resected tumors without pretreatment, 76%
      had regional nodal metastasis and 22% had spread to distant nodes. High-risk
      lymphatic areas were identified and selected for elective treatment. A
      standardized planning procedure was derived and tested under treatment
      conditions. CONCLUSIONS: Histopathologic data allowed us to develop
      recommendations for standardized treatment planning for ductal carcinoma of the
      pancreatic head. These are proposed for quality assurance in multicenter studies
      and routine use.

PMID- 15990005
TI  - Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection
      of primary gallbladder carcinoma: a 23-year experience.
AB  - PURPOSE: Primary adenocarcinoma of the gallbladder is a rare malignancy. To
      better define the role of adjuvant radiation therapy and chemotherapy, a
      retrospective analysis of the outcome of patients undergoing surgery and adjuvant
      therapy was undertaken. METHODS AND MATERIALS: Twenty-two patients with primary
      and nonmetastatic gallbladder cancer were treated with radiation therapy after
      surgical resection. Median radiation dose was 45 Gy. Eighteen patients received
      concurrent 5-fluorouracil (5-FU) chemotherapy. Median follow-up was 1.7 years in
      all patients and 3.9 years in survivors. RESULTS: The 5-year actuarial overall
      survival, disease-free survival, metastases-free survival, and local-regional
      control of all 22 patients were 37%, 33%, 36%, and 59%, respectively. Median
      survival for all patients was 1.9 years. CONCLUSION: Our series suggests that an
      approach of radical resection followed by external-beam radiation therapy with
      radiosensitizing 5-FU in patients with locally advanced, nonmetastatic carcinoma
      of the gallbladder may improve survival. This regimen should be considered in
      patients with resectable gallbladder carcinoma.

PMID- 15990006
TI  - Locoregional recurrence rates and prognostic factors for failure in node-negative
      patients treated with mastectomy: implications for postmastectomy radiation.
AB  - PURPOSE: Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence
      (LRR) of breast cancer. Survival appears improved in patients at higher risk for
      LRR. This study addresses whether subsets of node-negative patients with
      sufficiently high risk of LRR might benefit from PMRT. METHODS: Retrospective
      analysis of a cohort of 877 cases of node-negative breast cancer treated with
      mastectomy, without adjuvant radiation, from 1980 to 2000. RESULTS: Median follow
      up was 100 months. Ten-year cumulative incidence of LRR as first event was 6.0%.
      Size greater than 2 cm, margin less than 2 mm, premenopausal status, and
      lymphovascular invasion (LVI) were independently significant prognostic factors.
      Ten-year LRR was 1.2% for those with 0 risk factors, 10.0% for those with 1 risk
      factor, 17.9% for those with 2 risk factors, and 40.6% for those with 3 risk
      factors. The chest wall was the site of failure in 80% of patients. CONCLUSION:
      Postmastectomy radiation therapy has not been recommended for node-negative
      patients because the LRR rate is low in that population overall. This study
      suggests, however, that node-negative patients with multiple risk factors,
      including close margins, T2 or larger tumors, premenopausal status, and LVI, are
      at higher risk for LRR and might benefit from PMRT. Because the chest wall is the
      most common site of failure, treating the chest wall alone in these patients to
      minimize toxicity is reasonable.

PMID- 15990007
TI  - Clinicopathologic features and long-term outcome of patients with medullary
      breast carcinoma managed with breast-conserving therapy (BCT).
AB  - PURPOSE: The purpose of this study is to compare the clinical characteristics and
      outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in
      a large cohort of conservatively managed patients with long-term follow-up.
      METHODS AND MATERIALS: Chart records of patients with invasive breast cancer
      managed with breast-conserving therapy (BCT) at the therapeutic radiology
      facilities of Yale University School of Medicine before 2001 were reviewed. Forty
      six cases (1971-2001) were identified with medullary histology; 1,444 patients
      with infiltrating ductal carcinoma served as a control group. RESULTS: The
      medullary cohort presented at a younger age with a higher percentage of patients
      in the 35 years or younger age group (26.1% vs. 6.6%, p < 0.00001). Twelve
      patients with medullary histology underwent genetic screening, and 6 patients
      were identified with deleterious mutations. This group showed greater association
      with BRCA1/2 mutations compared with screened patients in the control group
      (50.0% vs. 15.8%, p = 0.0035). The medullary cohort was also significantly
      associated with greater T stage and tumor size (37.0% vs. 17.2% T2, mean size 3.2
      vs. 2.5 cm, p = 0.00097) as well as negative ER (84.9% vs. 37.6%, p < 0.00001)
      and PR (87.5% vs. 48.1%, p = 0.00001) status. As of February 2003, median follow
      up times for the medullary and control groups were 13.9 and 14.0 years,
      respectively. Although breast relapse-free rates were not significantly different
      (76.7% vs. 85.2%), 10-year distant relapse-free survival in the medullary cohort
      was significantly better than in the control group (94.9% vs. 77.5%, p = 0.028).
      CONCLUSIONS: Despite poor clinicopathologic features, patients with medullary
      histology demonstrate favorable long-term distant relapse-free survival. Local
      control rates of patients with medullary and infiltrating ductal carcinoma are
      comparable. These findings suggest that patients diagnosed with medullary
      carcinoma are appropriate candidates for BCT and are associated with favorable
      long-term prognosis.

PMID- 15990008
TI  - The patterns of care study for breast-conserving therapy in Japan: analysis of
      process survey from 1995 to 1997.
AB  - PURPOSE: To present the results of a process survey on breast-conserving therapy
      (BCT) in Japan from 1995 to 1997. METHODS AND MATERIALS: From September 1998 to
      December 1999, data on the treatment process of 865 randomly selected BCT
      patients were collected by extramural audits. RESULTS: For primary surgery, wide
      excision or tumorectomy was performed in 372 patients (43.0%), and quadrantectomy
      or segmental mastectomy was performed in 493 patients (57%). The extent of
      axillary dissection was equal or beyond Level II in 590 patients (68.2%).
      Systemic chemotherapy was administered to 103 of 160 node-positive patients
      (64.4%) and 180 of 569 node-negative patients (31.6%). Tamoxifen was administered
      to 234 of 323 hormone receptor-positive patients (72.5%) and 68 of 130 hormone
      receptor-negative patients (52.3%). Photon energy of 10 MV was administered for
      whole breast irradiation in 38 patients (4.4%) without bolus. CONCLUSIONS: The
      extent of surgical resection for BCT was large in Japan. Pathologic assessment
      and the technique of radiation therapy were apparently suboptimal in some cases.
      Information on prognostic/predictive factors was not fully utilized to
      individualize systemic adjuvant therapy. Establishment and widespread use of
      guidelines for BCT for in Japan are desirable. Repeated surveys will demonstrate
      how such guidelines affect clinical practices.

PMID- 15990009
TI  - Dose-volume modeling of salivary function in patients with head-and-neck cancer
      receiving radiotherapy.
AB  - PURPOSE: We investigated the factors that affect salivary function after head-and
      neck radiotherapy (RT), including parotid gland dose-volume effects, potential
      compensation by less-irradiated gland tissue, and functional recovery over time.
      METHODS AND MATERIALS: Sixty-five patients with head-and-neck tumors were
      enrolled in a prospective salivary function study. RT was delivered using
      intensity-modulated RT (n = 45), forward-planning three-dimensional conformal RT
      (n = 14), or three-dimensional conformal RT with an intensity-modulated RT boost
      (n = 6). Whole salivary flow was measured before therapy and at 6 months (n = 61)
      and 12 months (n = 31) after RT. A wide variety of dose-volume models to predict
      post-RT salivary function were tested. Xerostomia was defined according to the
      subjective, objective, management, analytic (SOMA) criteria as occurring when
      posttreatment salivary function was < 25% of the pretreatment function.
      Multivariate logistic regression analysis was used to assess the combined effect
      of dose-volume, patient-, and treatment-related factors. RESULTS: A significant
      correlation was observed between the relative quality-of-life scores and relative
      stimulated saliva values at 6 months after RT (Spearman's correlation coefficient
      [R(s)] = 0.46, p < 0.001). The dose-volume factors were by far the strongest
      correlates with stimulated saliva flow, although other factors showed modest
      significance in multimetric models (chemotherapy, gender, and Karnofsky
      performance status). Several fitted dose-volume models provided a good
      mathematical description of the data. Significant noise in the salivary
      measurements (repeated measurement coefficient of variation was 27% in normal
      subjects) precluded selection of any one of the models presented solely on the
      basis of the objective fit criteria. Nevertheless, the mean dose-exponential
      model, in which each parotid gland's relative salivary gland function equaled
      exp(-A x mean gland dose), with A equal to 0.054/Gy (68% confidence interval
      0.052-0.059), provided a good representation of the data and was incorporated
      into our multimetric analysis. Using that model, we estimated that a mean parotid
      dose of 25.8 Gy, on average, was likely to reduce a single parotid gland's flow
      to 25% of its pretreatment value, regardless of the treatment delivery method.
      Significant correlations were observed between a logistic multivariate model
      (incorporating the mean dose-exponential equation, gender, and Karnofsky
      performance status) and stimulated saliva flow at 6 months (R(s) = 0.73),
      stimulated saliva flow at 12 months (R(s) = 0.54), and quality-of-life score at 6
      months (R(s) = 0.35) after RT. CONCLUSION: Stimulated parotid salivary gland dose
      volume models strongly correlated with both stimulated salivary function and
      quality-of-life scores at 6 months after RT. The mean stimulated saliva flow
      rates improved from 6 to 12 months after RT. Salivary function, in each gland,
      appeared to be lost exponentially at a rate of approximately 5%/1 Gy of mean
      dose. Additional research is necessary to distinguish among the models for use in
      treatment planning. The incidence of xerostomia was significantly decreased when
      the mean dose of at least one parotid gland was kept to < 25.8 Gy with
      conventional fractionation. However, even lower mean doses imply increased late
      salivary function.

PMID- 15990010
TI  - Does altered fractionation influence the risk of radiation-induced optic
      neuropathy?
AB  - PURPOSE: To analyze the parameters that influence the risk of radiation-induced
      optic neuropathy (RION) after radiotherapy for head-and-neck tumors. METHODS AND
      MATERIALS: Between 1964 and 2000, 273 patients with tumors of the nasopharynx,
      paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were
      treated with curative intent and had radiation fields that included the optic
      nerves and/or chiasm. Patients were followed for at least 1 year after
      radiotherapy. RESULTS: Radiation-induced optic neuropathy developed in 32 eyes of
      24 patients (9%). The 5-year rates of freedom from RION according to the total
      dose and once- vs. twice-daily fractionation were as follows: < or =63 Gy once
      daily, 95%; < or =63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy
      twice daily, 91%. Multivariate analysis revealed that the total dose affected the
      risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice
      daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were
      marginally significant. The use of adjuvant chemotherapy did not significantly
      influence the likelihood of developing RION. CONCLUSION: The likelihood of
      developing RION is primarily influenced by the total dose. Hyperfractionation may
      reduce the risk of experiencing this complication.

PMID- 15990011
TI  - Salvage surgery after failure of very accelerated radiotherapy in advanced head
      and-neck squamous cell carcinoma.
AB  - PURPOSE: To assess the efficacy and toxicity of salvage surgery for local or
      cervical nodal recurrence after accelerated radiotherapy for locally advanced
      head-and-neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: We reviewed
      the medical records of the 136 patients with HNSCC who had been treated in three
      consecutive clinical trials at the Institut Gustave-Roussy using a very
      accelerated radiotherapy regimen (62 to 64 Gy with 2 daily fractions of 1.8 to 2
      Gy over 3.5 weeks). Sixty-nine patients of the 136 initial patients (51%) had
      local or neck lymph nodes relapse, or both. RESULTS: Sixteen of these 69 patients
      (23%) had undergone salvage surgery for recurrence locally (n = 8) or in the
      cervical nodes (n = 8). All 16 had initially been diagnosed with locally advanced
      oropharyngeal carcinoma (T4, 11 patients; T3, 5 patients), and 13 had initially
      had cervical node involvement. After salvage surgery, 6 patients had had a local
      recurrence; 7, cervical node recurrence; and 3, distant metastasis. Thus, salvage
      surgery had been successful only in 3 patients. The 3- and 5-year overall
      actuarial survival rates were 20% and 11%, respectively. Eight patients had major
      postoperative wound complications, including carotid rupture in three cases.
      CONCLUSION: Salvage surgery for relapse after very accelerated radiotherapy for
      advanced HNSCC is infrequently feasible and is of limited survival benefit. It
      should be used only in carefully selected cases.

PMID- 15990012
TI  - Radiation exposure and familial aggregation of cancers as risk factors for
      colorectal cancer after radioiodine treatment for thyroid carcinoma.
AB  - PURPOSE: In thyroid cancer patients, radioiodine treatment has been shown to be
      associated with an increased risk of colon carcinoma. The aim of this study in
      thyroid cancer patients was to evaluate the role of familial factors in the risk
      of colorectal cancer and their potential interaction with radioiodine exposure.
      METHODS AND MATERIALS: We performed a case-control study on 15 colorectal cancer
      patients and 76 matched control subjects, nested in a cohort of 3708 thyroid
      cancer patients treated between 1933 and 1998. For each patient, the radiation
      dose delivered to the colon by radioiodine was estimated by use of standard
      tables. In those who received external radiation therapy, the average radiation
      doses delivered to the colon and rectum were estimated by use of DOS_Eg software.
      A complete familial history was obtained by face-to-face interviews, and a
      familial index was defined to evaluate the degree of familial aggregation.
      RESULTS: The risk of colorectal cancer increased with familial aggregation of
      colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered
      to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95%
      CI, 1.0-8.0) for patients with at least one relative affected by colorectal
      cancer than for patients without such a family history (p = 0.05). The radiation
      dose delivered to the colon and rectum by (131)I and external radiation therapy
      was associated with an increase of risk near the significance threshold (p =
      0.1). No significant interaction was found between radiation dose and having an
      affected relative (p = 0.9). CONCLUSIONS: The role of familial background in the
      risk of colorectal cancer following a differentiated thyroid carcinoma appears to
      increase with the radiation dose delivered to the colon and rectum. However, the
      study population was small and no interaction was found between these two
      factors.

PMID- 15990013
TI  - Volume effects and region-dependent radiosensitivity of the parotid gland.
AB  - PURPOSE: To detect volume effects and possible regional differences in
      radiosensitivity of the rat parotid gland. METHODS AND MATERIALS: Parotid glands
      of male albino Wistar rats were locally X-irradiated, with collimators with
      conformal radiation portals used to supply 100% volume and 50% cranial/caudal
      partial volumes. High-resolution magnetic resonance imaging was used to provide
      the outlines of the parotid glands. Single doses of up to 40 Gy were applied, and
      the effects on saliva secretion, measured with the aid of miniaturized Lashley
      cups, were followed up to 365 days after the irradiation. RESULTS: Under
      conditions of equal mean absorbed doses and small variations in dose
      distribution, a pertinent volume effect was observed for late but not for early
      radiation damage. The late effects were different for the cranial part as
      compared with the caudal part of the parotid gland. The reduction in flow rate
      was much more severe after irradiation in the cranial part. After a single dose
      of 30 Gy, the reductions in flow rates were approximately 65% and 25% for the
      cranial and caudal parts, respectively. At that dose, no saliva flow was observed
      after irradiation of 100% of the gland. CONCLUSION: From the rat model studies
      presented, it is concluded that late radiation damage after partial irradiation
      of parotid glands shows region-dependent volume effects. This finding is expected
      to be relevant to the radiosensitivity of human salivary glands, and it implies
      that the predictive power of the mean dose concept in radiotherapeutic practice
      is limited. The finding of region-dependent late radiation damage also challenges
      the basic assumptions of most current normal tissue complication probability
      models for parotid gland function.

PMID- 15990014
TI  - What is the microscopic tumor extent beyond clinically delineated gross tumor
      boundary in nonmelanoma skin cancers?
AB  - PURPOSE: To quantify the microscopic tumor extension beyond clinically delineated
      gross tumor boundary in nonmelanoma skin cancers. METHODS AND MATERIALS: A
      prospective, single arm, study. Preoperatively, a radiation oncologist outlined
      the boundary of a gross lesion, and drew 5-mm incremental marks in four
      directions from the delineated border. Under local anesthesia, the lesion was
      excised, and resection margins were assessed microscopically by frozen section.
      Once resection margins were clear, the microscopic tumor extent was calculated
      using the presurgical incremental markings as references. A potential
      relationship between the distance of microscopic tumor extension and other
      variables was analyzed. RESULTS: A total of 71 lesions in 64 consecutive
      patients, selected for surgical excision with frozen-section-assisted assessment
      of resection margins, were accrued. The distance of microscopic tumor extension
      beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin
      of 10 mm was required to provide a 95% chance of obtaining clear resection
      margins. The microscopic tumor extent was positively correlated with the size of
      gross lesion, but not with other variables. CONCLUSIONS: The distance of
      microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable,
      with a mean of 5.2 mm. Such information is critical for the proper radiation
      planning of skin cancer therapy.

PMID- 15990015
TI  - Assessment of the tumor microenvironment in cervix cancer using dynamic contrast
      enhanced CT, interstitial fluid pressure and oxygen measurements.
AB  - PURPOSE: Interstitial fluid pressure (IFP) and oxygen (pO(2)) measurements are
      prognostic factors in cervical cancer. The purpose of this study was to determine
      the relationship between IFP and oxygenation and parameters derived from dynamic
      contrast-enhanced computed tomography (DCE-CT). METHODS AND MATERIALS: Dynamic
      contrast-enhanced computed tomography was performed in 32 patients with cervical
      cancer before radiation therapy. Images were acquired during intravenous contrast
      injection at 1 per s for 120 s and 1 per 15 s for 60 s. DCE-CT was analyzed using
      CT Perfusion 3 software (GE Medical Systems) to derive tumor blood flow (BF),
      permeability surface area product, blood volume, and mean transit time. Further
      analysis was performed to obtain relative peak enhancement, residual enhancement
      at 3 min after contrast injection (RE), time to peak and initial slope. Nodal
      status and tumor size were assessed with MRI. From in vivo IFP (n = 31) and pO(2)
      (n = 31) tumor measurements median pO(2) (mO(2)), percentage measurements less
      than 5 mm Hg (HP5) and mean IFP values were calculated. RESULTS: There was a
      positive correlation between BF and mO(2) (r = 0.47, p = 0.007) and between RE
      and HP5 (r = 0.39, p = 0.03). There was no correlation between IFP and DCE-CT
      parameters. CONCLUSION: There is a moderately positive, correlation between tumor
      oxygenation and BF as well as RE and HP5. Further study is required to determine
      if DCE-CT parameters are useful predictors of tumor behavior in cervical cancer.

PMID- 15990016
TI  - Comparison of low and high dose rate brachytherapy in the treatment of uterine
      cervix cancer. Retrospective analysis of two sequential series.
AB  - PURPOSE: This retrospective analysis aims to report on the comparative outcome of
      cervical cancer patients treated with low dose rate (LDR) and high dose rate
      (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were
      treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001,
      118 patients were treated with high dose rate (HDR) brachytherapy (HDR group).
      FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and
      Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage
      III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy
      (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for
      patients treated with 1 and 2 implants, respectively. All patients from the HDR
      group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival,
      disease-free survival, local control, and late complications at 5 years, were
      endpoints compared for both groups. RESULTS: Median follow-up time for LDR and
      HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117
      months), respectively. For all stages combined, overall survival, disease-free
      survival, and local control at 5 years were better in the LDR group (69% vs. 55%,
      p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For
      clinical Stages I and II, no differences was seen in overall survival, disease
      free survival, and local control at 5 years between the two groups. For clinical
      Stage III, overall survival and disease-free survival at 5 years were better in
      the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p =
      0.03, respectively), and local control was marginally higher in the LDR group
      than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal
      complications was higher in the LDR group than in the HDR group (16% vs. 8%, p =
      0.03) and 5-year probability of small bowel and urinary complications was not
      statistically different between the the LDR group and the HDR group (4.6% vs.
      8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This
      comparative series suggests similar outcome for Stages I and II patients treated
      with either HDR or LDR brachytherapy. Lower overall and disease-free survival and
      marginally lower local control were observed for Stage III patients treated with
      HDR brachytherapy. Less late rectal complications were observed in the HDR group
      patients. These findings were probably the result of the relatively low HDR
      brachytherapy dose delivered at Point A.

PMID- 15990017
TI  - Intensity-modulated radiation therapy after hysterectomy: comparison with
      conventional treatment and sensitivity of the normal-tissue-sparing effect to
      margin size.
AB  - PURPOSE: To determine the influence of target-volume expansion on the reduction
      in small-bowel dose achieved with use of intensity-modulated radiation therapy
      (IMRT) vs. standard conformal treatment of the pelvis after hysterectomy, and to
      investigate the influence of patient body habitus on the normal-tissue sparing
      achieved with use of IMRT. METHODS AND MATERIALS: A clinical target volume (CTV)
      was contoured on each of 10 planning computed tomography scans of patients who
      had been treated for cervical or endometrial cancer after a hysterectomy.
      Treatment planning was based on vaginal CTVs and regional nodal CTVs. To account
      for internal motion, margins were added to form an initial planning target volume
      (PTVA) as follows: 0.0 mm were added to the regional nodal CTV; 10 mm were added
      anteriorly to the vaginal CTV; and 5 mm were added to the vaginal CTV in all
      other directions. Two further PTVs (PTVB and PTVC) were produced by a 5-mm
      expansion of PTVA to give PTVB and a further 5-mm expansion to give PTVC.
      Treatment plans for all 3 PTVs were produced by use of 2 conformal fields (2FC),
      4 conformal fields (4FC), or IMRT to deliver 45 Gy to more than 97% of the PTV.
      The primary goal of IMRT was to spare small bowel. The change in sparing that
      accompanied the increase in margin size was assessed by comparison of dose-volume
      histograms that resulted from PTVA, PTVB, and PTVC. Measured patient dimensions
      were correlated with bowel sparing. RESULTS: Significantly less small bowel was
      irradiated by IMRT than by 2FC (p < 0.0001) or 4FC (p < 0.0001) for doses greater
      than 25 Gy. Significantly less rectum was irradiated by IMRT than by 2FC (p <
      0.0001) or 4FC (p < 0.0001). Significantly less bladder was irradiated by IMRT
      than by 2FC (p < 0.0001). However, the magnitude of the sparing achieved by use
      of IMRT decreased as margins increased. In particular, the volume of small bowel
      spared by IMRT vs. 2FC or 4FC decreased as margin size increased (p = 0.0002 and
      p = 0.008 for 2FC and 4FC, respectively). The amount of normal-tissue sparing
      achieved by use of IMRT vs. 4FC was inversely correlated with patient body mass
      index. CONCLUSION: Because the small-bowel sparing achieved with use of IMRT is
      markedly reduced by relatively small expansions of the target volume, accurate
      target delineation, highly reproducible patient immobilization, and a clear
      understanding of internal-organ motion are needed to achieve optimal advantage in
      the use of IMRT over conventional methods of posthysterectomy pelvic radiation
      therapy.

PMID- 15990018
TI  - The impact of whole-brain radiation therapy on the long-term control and
      morbidity of patients surviving more than one year after gamma knife radiosurgery
      for brain metastases.
AB  - PURPOSE: To better analyze how whole-brain radiotherapy (WBXRT) affects long-term
      tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for
      brain metastases, we studied these outcomes in patients who had survived at least
      1 year from SRS. METHODS AND MATERIALS: We evaluated the results of gamma knife
      radiosurgery for 160 brain metastases in 110 patients who were followed for a
      median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a
      solitary brain metastasis and 28 patients had multiple metastases. Seventy
      patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas
      40 patients (44 lesions) initially received radiosurgery alone. Median treatment
      volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in
      the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy). RESULTS: At
      1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%, 68.6% +/- 8.7%, and
      68.6% +/- 8.7% with SRS alone compared with 93.1% +/- 2.4%, 87.7% +/- 4.9%, and
      65.7% +/- 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found
      that WBXRT improved local control in patient subsets tumor volume > or =2 cc,
      peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and
      lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal
      intracranial failure developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/-
      9.4%, and 74.5% +/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/-
      8.7%, and 61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a
      trend for improved distal intracranial control with WBXRT for only
      nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in
      2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was unaffected by WBXRT
      (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or
      in any subsets. CONCLUSIONS: In this retrospective study of 1-year survivors of
      SRS for brain metastases, the addition of concurrent WBXRT to SRS was associated
      with an improved local control rate in patient subsets with tumor volume > or =2
      cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and
      specifically lung cancer metastases. A trend was noted for improved distal
      intracranial control for patients having nonradioresistant tumors. Distant
      intracranial relapse >1 year posttreatment is a significant problem with or
      without initial WBXRT.

PMID- 15990019
TI  - Treatment of recurrent glioblastoma multiforme with GliaSite brachytherapy.
AB  - PURPOSE: In this study, we assess the efficacy of GliaSite brachytherapy in the
      treatment of patients with recurrent glioblastoma multiforme (GBM). METHODS AND
      MATERIALS: Between 1999 and 2004, 24 patients with recurrent glioblastoma
      multiforme were treated with the GliaSite Radiation Therapy System (RTS). The
      GliaSite is an inflatable balloon catheter that is placed in the resection cavity
      at the time of surgical resection. Low-dose-rate radiation is then delivered
      locally by temporarily inflating the balloon with an aqueous solution of
      organically bound (125)I (Iotrex [sodium 3-((125)I)-iodo-4
      hydroxybenzenesulfonate]). Patients at the Johns Hopkins Hospital with recurrent
      GBM, who were previously treated with surgery and external beam radiotherapy,
      underwent surgical resection followed by GliaSite balloon implantation.
      Subsequently, the patients received radiation therapy using the GliaSite to a
      mean dose of 53.1 Gy. Ten patients were male, and 14 patients were female. The
      mean age was 48.1 years. All patients had pathologically confirmed recurrent GBM.
      The median Karnofsky performance status (KPS) was 80. Median follow-up time was
      21.8 months. RESULTS: At the time of analysis, 18 patients (75%) had died; 6
      patients (25%) were alive. Median survival from diagnosis for all patients was
      23.3 months. Median survival after GliaSite brachytherapy was 9.1 months.
      Patients with a KPS > or =70 had a median survival of 9.3 months, whereas
      patients with a KPS <70 had a median survival of 3.1 months (p < 0.003). Survival
      was not significantly different between patients receiving 45 Gy and patients
      receiving a dose greater than 45 Gy. Acute side effects were minor, consisting of
      mild nausea and/or headache. One patient developed a wound infection. No
      incidents of meningitis were observed. Late sequelae were rare, but 2 incidents
      of symptomatic radiation necrosis were observed. One patient developed transient
      expressive aphasia. CONCLUSIONS: GliaSite radiotherapy confers a prolongation of
      survival in patients with recurrent glioblastoma multiforme compared to
      historical controls with recurrent GBM. GliaSite therapy leads to a favorable
      survival outcome of 9.3 months in patients with KPS > or =70, but only 3.1 months
      in patients with KPS <70. Favorable survival is observed for patients within each
      recursive partitioning analysis class. Treatment with GliaSite is safe and
      generally well tolerated. Additional data are needed to fully assess the
      therapeutic benefit of GliaSite brachytherapy for recurrent GBM.

PMID- 15990020
TI  - Radiation-induced damage to normal tissues after radiotherapy in patients treated
      for gynecologic tumors: association with single nucleotide polymorphisms in
      XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in
      lymphocytes.
AB  - PURPOSE: To examine the association of polymorphisms in XRCC1 (194Arg/Trp,
      280Arg/His, 399Arg/Gln, 632Gln/Gln), XRCC3 (5' UTR 4.541A>G, IVS5-14 17.893A>G,
      241Thr/Met), and OGG1 (326Ser/Cys) with the development of late radiotherapy (RT)
      reactions and to assess the correlation between in vitro chromosomal
      radiosensitivity and clinical radiosensitivity. METHODS AND MATERIALS: Sixty-two
      women with cervical or endometrial cancer treated with RT were included in the
      study. According to the Common Terminology Criteria for Adverse Events, version
      3.0, scale, 22 patients showed late adverse RT reactions. Polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) assays were
      performed to examine polymorphic sites, the G2 assay was used to measure
      chromosomal radiosensitivity, and patient groups were compared using actuarial
      methods. RESULTS: The XRCC3 IVS5-14 polymorphic allele was significantly
      associated with the risk of developing late RT reactions (odds ratio 3.98, p =
      0.025), and the XRCC1 codon 194 variant showed a significant protective effect (p
      = 0.028). Patients with three or more risk alleles in XRCC1 and XRCC3 had a
      significantly increased risk of developing normal tissue reactions (odds ratio
      10.10, p = 0.001). The mean number of chromatid breaks per cell was significantly
      greater in patients with normal tissue reactions than in patients with no
      reactions (1.16 and 1.34, respectively; p = 0.002). Patients with high
      chromosomal radiosensitivity showed a 9.2-fold greater annual risk of
      complications than patients with intermediate chromosomal radiosensitivity.
      Combining the G2 analysis with the risk allele model allowed us to identify 23%
      of the patients with late normal tissue reactions, without false-positive
      results. CONCLUSION: The results of the present study showed that clinical
      radiosensitivity is associated with an enhanced G2 chromosomal radiosensitivity
      and is significantly associated with a combination of different polymorphisms in
      DNA repair genes.

PMID- 15990021
TI  - Inclusion of biological factors in parallel-architecture normal-tissue
      complication probability model for radiation-induced liver disease.
AB  - PURPOSE: To include biologic factors in parallel-architecture normal-tissue
      complication probability (NTCP) model for radiation-induced liver disease (RILD)
      after three-dimensional conformal radiotherapy (3D-CRT) for gastric or hepatic
      cancer. METHODS AND MATERIALS: A total of 151 patients (89 with hepatocellular
      carcinoma and 62 with gastric cancer) who received 3D-CRT to the liver were
      included (isocenter dose range 33.0 to 66.0 Gy; mean 48.0 Gy). RILD was defined
      as grade 3 or higher liver toxicity according to Common Toxicity Criteria Version
      2.0 of the National Cancer Institute within 4 months after 3D-CRT. Possible
      correlations of patient-related or dosimetric factors with RILD were tested.
      Maximum-likelihood analysis estimated NTCP model parameters for group and
      subgroups. Goodness-of-fit analysis estimated deviance of NTCP model parameters
      between subgroups. RESULTS: RILD developed in 25 patients. Hepatitis B virus
      carrier status (p < 0.001) was the only significant independent factor. The 4
      parallel NTCP model parameters, mean functional reserve (V(50)), width of
      functional reserve distribution (sigma), dose damage to 50% of liver subunits
      (D(50)), and slope parameter for subunit dose-response (k), were respectively,
      0.54, 0.14, 50 Gy, 0.18 (group); 0.53, 0.07, 50 Gy, 4.6 x 10(-7) (carriers);
      0.59, 0.12, 25 Gy, 59.8 (noncarriers). In carrier-state subgroups, goodness-of
      fit deviance with 1 subgroup's parameter set would have been worse in the other
      group. Across subgroups, patients with RILD all had liver fraction damage (f)
      greater than 0.4 compared with wider distribution for the whole group.
      CONCLUSIONS: RILD is described with a parallel-architecture NTCP model for HBV
      carriers and noncarriers with a threshold effect greater than 0.4. The main
      difference is in slope parameter for subunit dose-response.

PMID- 15990022
TI  - Thymidine analogues to assess microperfusion in human tumors.
AB  - PURPOSE: To validate the use of the thymidine analogues as local perfusion
      markers in human tumors (no labeling indicates no perfusion) by comparison with
      the well-characterized perfusion marker Hoechst 33342. METHODS AND MATERIALS:
      Human tumor xenografts from gliomas and head-and-neck cancers were injected with
      iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye
      Hoechst 33342. In frozen sections, each blood vessel was scored for the presence
      of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of
      analogue-negative vessels was compared with the fraction of Hoechst-negative
      vessels. Collocalization of the two markers was also scored. RESULTS: We found
      considerable intertumor variation in the fraction of perfused vessels, measured
      by analogue labeling, both in the human tumor xenografts and in a series of tumor
      biopsies from head-and-neck cancer patients. There was a significant correlation
      between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts
      (r = 85, p = 0.0004), despite some mismatches on a per-vessel basis. CONCLUSIONS:
      Thymidine analogues can be successfully used to rank tumors according to their
      fraction of perfused vessels. Whether this fraction correlates with the extent of
      acute hypoxia needs further confirmation.

PMID- 15990023
TI  - Effects of motexafin gadolinium on DNA damage and X-ray-induced DNA damage
      repair, as assessed by the Comet assay.
AB  - PURPOSE: To investigate the effects of motexafin gadolinium (MGd) on the levels
      of reactive oxygen species (ROS), glutathione (GSH), and DNA damage in EMT6 mouse
      mammary carcinoma cells. The ability of MGd to alter radiosensitivity and to
      inhibit DNA damage repair after X-ray irradiation was also evaluated. METHODS AND
      MATERIALS: Reactive oxygen species and GSH levels were assessed by 2,7
      dichlorofluorescein fluorescence flow cytometry and the Tietze method,
      respectively. Cellular radiosensitivity was assessed by clonogenic assays.
      Deoxyribonucleic acid damage and DNA damage repair were assessed in plateau-phase
      EMT6 cells by the Comet assay and clonogenic assays. RESULTS: Cells treated with
      100 mumol/L MGd plus equimolar ascorbic acid (AA) had significantly increased
      levels of ROS and a 58.9% +/- 3.4% decrease in GSH levels, relative to controls.
      Motexafin gadolinium plus AA treatment increased the hypoxic, but not the
      aerobic, radiosensitivity of EMT6 cells. There were increased levels of single
      strand breaks in cells treated with 100 mumol/L MGd plus equimolar AA, as
      evidenced by changes in the alkaline tail moment (MGd + AA, 6 h: 14.7 +/- 1.8;
      control: 2.8 +/- 0.9). The level of single-strand breaks was dependent on the
      length of treatment. Motexafin gadolinium plus AA did not increase double-strand
      breaks. The repair of single-strand breaks at 2 h, but not at 4 h and 6 h, after
      irradiation was altered significantly in cells treated with MGd plus AA (MGd +
      AA, 2 h: 15.8 +/- 3.4; control: 5.8 +/- 0.6). Motexafin gadolinium did not alter
      the repair of double-strand breaks at any time after irradiation with 10 Gy.
      CONCLUSIONS: Motexafin gadolinium plus AA generated ROS, which in turn altered
      GSH homeostasis and induced DNA strand breaks. The MGd plus AA-mediated
      alteration of GSH levels increased the hypoxic, but not aerobic, radiosensitivity
      of EMT6 cells. Motexafin gadolinium altered the kinetics of single-strand break
      repair soon after irradiation but did not inhibit potentially lethal damage
      repair in EMT6 cells.

PMID- 15990024
TI  - On the mechanism of salivary gland radiosensitivity.
AB  - PURPOSE: To contribute to the understanding of the enigmatic radiosensitivity of
      the salivary glands by analysis of appropriate literature, especially with
      respect to mechanisms of action of early radiation damage, and to supply
      information on the possibilities of amelioration of radiation damage to the
      salivary glands after radiotherapy of head-and-neck cancer. METHODS AND
      MATERIALS: Selected published data on the mechanism of salivary gland
      radiosensitivity and radioprotection were studied and analyzed. RESULTS: From a
      classical point of view, the salivary glands should not respond as rapidly to
      radiation as they appear to do. Next to the suggestion of massive apoptosis, the
      leakage of granules and subsequent lysis of acinar cells was suggested to be
      responsible for the acute radiation-induced function loss of the salivary glands.
      The main problem with these hypotheses is that recently performed assays show no
      cell loss during the first days after irradiation, while saliva flow is
      dramatically diminished. The water secretion is selectively hampered during the
      first days after single-dose irradiation. Literature is discussed that shows that
      the compromised cells suffer selective radiation damage to the plasma membrane,
      disturbing signal transduction primarily affecting watery secretion. Although the
      cellular composition of the submandibular gland and the parotid gland are
      different, the damage response is very alike. The acute radiation-induced
      function loss in both salivary glands can be ameliorated by prophylactic
      treatment with specific receptor agonists. CONCLUSIONS: The most probable
      mechanism of action, explaining the enigmatic high radiosensitivity for early
      effects, is selective radiation damage to the plasma membrane of the secretory
      cells, disturbing muscarinic receptor stimulated watery secretion. Later damage
      is mainly due to classical mitotic cell death of progenitor cells, leading to a
      hampered replacement capacity of the gland for secretory cells, but is also
      caused by damage to the extracellular environment, preventing proper cell
      functioning.

PMID- 15990025
TI  - The calculated risk of fatal secondary malignancies from intensity-modulated
      radiation therapy.
AB  - PURPOSE: Out-of-field radiation doses to normal tissues may be associated with an
      increased risk of secondary malignancies, particularly in long-term survivors.
      Step-and-shoot intensity-modulated radiation therapy (IMRT), an increasingly
      popular treatment modality, yields higher out-of-field doses than do conventional
      treatments, because of an increase in required monitor units (beam-on time).
      METHODS: We used published risk coefficients (NRCP Report 116) and out-of-field
      dose equivalents to multiple organ sites to estimate a conservative maximal risk
      of fatal secondary malignancy associated with 6 IMRT approaches and 1
      conventional external-beam approach for prostate cancer. RESULTS: Depending on
      treatment energy, the IMRT treatments required 3.5-4.9 times as many monitor
      units to deliver as did the conventional treatment. The conservative maximum risk
      of fatal second malignancy was 1.7% for conventional radiation, 2.1% for IMRT
      using 10-MV X-rays, and 5.1% for IMRT using 18-MV X-rays. Intermediate risks were
      associated with IMRT using 6-MV X-rays: 2.9% for treatment with the Varian
      accelerator and 3.7% for treatment with the Siemens accelerator, as well as using
      15-MV X-rays: 3.4% (Varian) and 4.0% (Siemens). CONCLUSION: The risk of fatal
      secondary malignancy differed substantially between IMRT and conventional
      radiation therapy for prostate cancer, as well as between different IMRT
      approaches. Perhaps this risk should be considered when choosing the optimal
      treatment technique and delivery system for patients who will undergo prostate
      radiation.

PMID- 15990026
TI  - Out-of-field photon and neutron dose equivalents from step-and-shoot intensity
      modulated radiation therapy.
AB  - PURPOSE: To measure the photon and neutron out-of-treatment-field dose
      equivalents to various organs from different treatment strategies (conventional
      vs. intensity-modulated radiation therapy [IMRT]) at different treatment energies
      and delivered by different accelerators. METHODS AND MATERIALS: Independent
      measurements were made of the photon and neutron out-of-field dose equivalents
      resulting from one conventional and six IMRT treatments for prostate cancer. The
      conventional treatment used an 18-MV beam from a Clinac 2100; the IMRT treatments
      used 6-MV, 10-MV, 15-MV, and 18-MV beams from a Varian Clinac 2100 accelerator
      and 6-MV and 15-MV beams from a Siemens Primus accelerator. Photon doses were
      measured with thermoluminescent dosimeters in a Rando phantom, and neutron
      fluence was measured with gold foils. Dose equivalents to the colon, liver,
      stomach, lung, esophagus, thyroid, and active bone marrow were determined for
      each treatment approach. RESULTS: For each treatment approach, the relationship
      between dose equivalent per MU, distance from the treatment field, and depth in
      the patient was examined. Photon dose equivalents decreased approximately
      exponentially with distance from the treatment field. Neutron dose equivalents
      were independent of distance from the treatment field and decreased with
      increasing tissue depth. Neutrons were a significant contributor to the out-of
      field dose equivalent for beam energies > or =15 MV. CONCLUSIONS: Out-of-field
      photon and neutron dose equivalents can be estimated to any point in a patient
      undergoing a similar treatment approach from the distance of that point to the
      central axis and from the tissue depth. This information is useful in determining
      the dose to critical structures and in evaluating the risk of associated
      carcinogenesis.

PMID- 15990027
TI  - Intensity-modulated radiotherapy technique for three-field breast treatment.
AB  - PURPOSE: To develop a simplified intensity-modulated radiotherapy (IMRT)
      algorithm for three-field breast treatment using a single isocenter setup. The
      algorithm aims to deliver a uniform dose throughout the breast volume. Special
      attention was paid to the highly divergent nature of the beam configuration.
      METHODS AND MATERIALS: Computed tomography (CT) image setup of the patient was
      acquired. On each CT slice, the computer automatically generated lines parallel
      to the posterior edge of the tangent field. The mid-point of each line segment
      that intersected the breast was determined and the dose from an open field
      calculated. The intensity of the divergent pencil beam corresponding to the mid
      point was set to be inversely proportional to the open field dose to the mid
      point. Forward dose calculation was then performed using this intensity
      distribution. RESULTS: A total of 15 breast cancer patients undergoing three
      field IMRT who underwent planning and treatment with this algorithm were included
      in this study. Compared with standard wedged pair tangents, the IMRT plan
      produced statistically significant better dose distributions in terms of target
      coverage and target dose uniformity, as well as reduced dose to the contralateral
      breast and reduced hot spots to the ipsilateral lung. CONCLUSION: Since March
      2004, the new IMRT algorithm has been used for planning and treatment of > 20
      patients undergoing three-field treatment, as well as >200 patients undergoing
      regular two-field tangent treatment, all with excellent dose distributions
      throughout the breast volume.

PMID- 15990028
TI  - Accuracy of daily image guidance for hypofractionated liver radiotherapy with
      active breathing control.
AB  - PURPOSE: A six-fraction, high-precision radiotherapy protocol for unresectable
      liver cancer has been developed in which active breathing control (ABC) is used
      to immobilize the liver and daily megavoltage (MV) imaging and repositioning is
      used to decrease geometric uncertainties. We report the accuracy of setup in the
      first 20 patients consecutively treated using this approach. METHODS AND
      MATERIALS: After setup using conventional skin marks and lasers, orthogonal MV
      images were acquired with the liver immobilized using ABC. The images were
      aligned to reference digitally reconstructed radiographs using the diaphragm for
      craniocaudal (CC) alignment and the vertebral bodies for anterior-posterior (AP)
      and mediolateral (ML) alignment. Adjustments were made for positioning errors >3
      mm. Verification imaging was repeated after repositioning to assess for residual
      positioning error. Offline image matching was conducted to determine the setup
      accuracy using this approach compared with the initial setup error before
      repositioning. Real-time beam's-eye-view MV movies containing an air-diaphragm
      interface were also evaluated. RESULTS: A total of 405 images were evaluated from
      20 patients. Repositioning occurred in 109 of 120 fractions because of offsets >3
      mm. Three to eight beam angles, with up to four segments per field, were used for
      each isocenter. Breath holds of up to 27 s were used for imaging and treatment.
      The average time from the initial verification image to the last treatment beam
      was 21 min. Image guidance and repositioning reduced the population random setup
      errors (sigma) from 6.5 mm (CC), 4.2 mm (ML), and 4.7 mm (AP) to 2.5 mm (CC), 2.8
      mm (ML), and 2.9 mm (AP). The average individual random setup errors (sigma) were
      reduced from 4.5 mm (CC), 3.2 mm (AP), and 2.5 mm (ML) to 2.2 mm (CC), 2.0 mm
      (AP), and 2.0 mm (ML). The standard deviation of the distribution of systematic
      deviations (Sigma) was also reduced from 5.1 mm (CC), 3.4 mm (ML), and 3.1 mm
      (AP) to 1.4 mm (CC), 2.0 mm (ML), and 1.9 mm (AP) with image guidance and
      repositioning. The average absolute systematic errors were reduced from 4.1 mm
      (CC), 2.4 mm (AP), and 3.1 (ML) to 1.1 mm (CC), 1.3 mm (AP), and 1.6 mm (ML).
      Analysis of 52 real-time beam's-eye-view MV movies revealed an average absolute
      CC offset in diaphragm position of 1.9 mm. CONCLUSION: Image guidance with
      orthogonal MV imaging and ABC for stereotactic body radiotherapy for liver cancer
      is feasible, improving setup accuracy compared with ABC without daily imaging and
      repositioning.

PMID- 15990030
TI  - PSA failure and the risk of death in prostate cancer patients treated with
      radiotherapy: in regard to Kwan et al. (Int J Radiat Oncol Biol Phys 2004;60:1040
      1046).

PMID- 15990031
TI  - Activation patterns of epidermal growth factor-receptor signaling in glioblastoma
      multiforme: in regard to Chakravarti et al. (Int J Radiat Oncol Biol Phys
      2005;62:318-327).

PMID- 15990032
TI  - Malpractice in radiation oncology: redefining the role of the medical expert: in
      regard to Kagan (Int J Radiat Oncol Biol Phys 2005;61:638-639).

PMID- 15990035
TI  - PET-CT for tumor delineation: in regard to Heron et al. (Int J Radiat Oncol Biol
      Phys 2004;60:1419-1424).

PMID- 15990038
TI  - Mechanical embolectomy.
AB  - Mechanical embolectomy in acute ischemic stroke employs the use of novel
      endovascular devices to revascularize occluded intracerebral arteries. Devices
      like the Merci Retiever and other endovascular snares, laser thrombectomy and
      rheolytic/obliterative microcatheters, intracranial balloon angioplasty and
      stenting, and intra-arterial and transcranial ultrasound-enhanced chemical
      thrombolysis are intended to improve tissue rescue and diminish reperfusion
      hemorrhage while broadening the population eligible for therapy. Patient
      selection with MRI- and CT-based stroke protocols can detect tissue at risk and
      may obviate the classic limitations of the stroke therapeutic time window. These
      devices are being developed and modified at a rapid pace, requiring mounting
      endovascular expertise, and are being used successfully alone or in conjunction
      with chemical thrombolysis with relative safety.

PMID- 15990039
TI  - Clipping or coiling of cerebral aneurysms.
AB  - The management of a patient with a cerebral aneurysm is complex, and two accepted
      treatment modalities are now available. The superiority of either of the
      treatment options has not been defined, but data are now available with regard to
      the safety and efficacy of each modality and can be used to decide what is best
      for individual patients when combined with other important variables, such as the
      patient's expected longevity, specific aneurysm factors (eg, size, dome-to-neck
      ratio, location), and operator's experience. This complex decision entertaining
      all the variables should ensure that patients receive the most appropriate care.
      New developments in the endovascular management of cerebral aneurysms are likely
      to alter this algorithm.

PMID- 15990040
TI  - Healing of intracranial aneurysms with bioactive coils.
AB  - Inadequate healing is an important mechanism for aneurysm development and
      recanalization after embolization. Matrix coils have been shown by experimental
      studies to enhance vascular repair and fibrosis, thus reducing the risk of
      recanalization. The clinical application of Matrix coils represents the
      transition from pure mechanical occlusion to adjunct biologic healing of
      aneurysms. Our preliminary clinical experience reveals evidence of a healing
      response in aneurysms treated with Matrix coils. This technology can be further
      improved through the incorporation of new knowledge on the molecular pathogenesis
      of aneurysms and the cellular and molecular mechanisms of healing.

PMID- 15990041
TI  - Endovascular treatment of cerebral vasospasm: transluminal balloon angioplasty,
      intra-arterial papaverine, and intra-arterial nicardipine.
AB  - Cerebral vasospasm is still one of the leading causes of morbidity and mortality
      from subarachnoid hemorrhage. Vasospasm refractory to medical management can be
      treated with endovascular therapies, such as transluminal balloon angioplasty or
      infusion of intra-arterial vasodilating agents. In our review of clinical series
      reported in the English language literature, transluminal balloon angioplasty
      produced clinical improvement in 62% of patients, significantly improved mean
      transcranial Doppler (TCD) velocities(P <.05), significantly improved cerebral
      blood flow (CBF) in 85% of patients as studied by (133)Xenon techniques and
      serial single photon emission computerized tomography,and was associated with
      5.0% complications and 1.1% vessel rupture. Intra-arterial papaverine therapy
      produced clinical improvement in 43% of patients but only transiently,requiring
      multiple treatment sessions (1.7 treatments per patient); significantly improved
      mean TCD velocities (P <.01) but only for less than 48 hours; improved CBF in 60%
      of patients but only for less than 12 hours; and was associated with increases in
      intracranial pressure and 9.9% complications. Intra-arterial nicardipine therapy
      produced clinical improvement in 42% of patients, significantly improved mean TCD
      velocities (P <.001) for 4 days, and was associated with no complications in our
      small series. We have adopted a treatment protocol at our institution of
      transluminal balloon angioplasty and intra-arterial nicardipine therapy as the
      endovascular treatments for medically refractory cerebral vasospasm.

PMID- 15990042
TI  - Antiplatelet therapy in neuroendovascular therapeutics.
AB  - Our understanding of the pharmacology of antiplatelet therapy continues to evolve
      rapidly. Although the existing data are primarily generated in the setting of
      interventional and preventative cardiology studies, these data may be
      extrapolated to guide the rational application of these agents in
      neuroendovascular procedures. Platelet function testing represents an
      increasingly available and practical method by which to verify the adequacy of
      therapy and guide clinical decision making. The optimal application of these
      agents will undoubtedly improve the risk profile of neuroendovascular procedures,
      increase the success rate of acute stroke intervention, and facilitate more
      effective secondary stroke prevention.

PMID- 15990043
TI  - Intensive care unit management of interventional neuroradiology patients.
AB  - The management of interventional neurologic patients in the intensive care unit
      is based on their underlying disease for the most part. Patients with ischemic
      stroke are largely managed like patients with ischemic stroke who have not
      undergone interventional procedures, and the same is true for those with an
      aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage secondary to an
      arteriovenous malformation, for example.Having said this, there are some special
      considerations that require special mention when it comes to managing patients
      after catheter-based procedures.

PMID- 15990044
TI  - Interventional neuroradiology adjuncts and alternatives in patients with head and
      neck vascular lesions.
AB  - Vascular lesions of the head and neck can result from a variety of neoplastic and
      traumatic conditions that may cause local neurologic symptoms or may compromise
      the carotid or vertebral arteries, leading to ischemic deficits. Management of
      lesions involving vascular structures at the skull base may require a temporary
      balloon occlusion tolerance test or endovascular transarterial embolization as
      part of the preoperative management. Endovascular techniques can also be used as
      a salvage measure for severe head and neck bleeding and can assist with the
      management of vascular injury occurring in the operative or perioperative
      setting. Familiarity with the role of endovascular techniques in this group of
      patients may favorably influence patient management and outcome.

PMID- 15990045
TI  - Percutaneous spinal interventions.
AB  - Interventional neuroradiology procedures of the spine are being performed with
      increasing frequency. These therapies complement and, in some cases, replace more
      conventional operations of the vertebral column and its contents. This article
      surveys the background, present application, and future horizons of several
      minimally invasive spinal interventions, including vertebroplasty and
      kyphoplasty, microcatheterization of the cervical epidural space via lumbar
      puncture for drug delivery, percutaneous intraspinal navigation, and percutaneous
      spinal fixation.

PMID- 15990048
TI  - Endoscopic therapy for Barrett's esophagus.
AB  - With the increase in the rate of esophageal adenocarcinoma in the United States
      and the Western world matched with the high morbidity and mortality of
      esophagectomy, there is an increasing need for new and effective techniques to
      treat and prevent esophageal adenocarcinoma. A wide variety of endoscopic mucosal
      ablative techniques have been developed for early esophageal neoplasia. However,
      long-term control of neoplasic risk has not been demonstrated. Most studies show
      that specialized intestinal metaplasia may persist underneath neo-squamous
      mucosa, posing a risk for subsequent neoplastic progression. In this article we
      review current published literature on endoscopic therapies for the management of
      Barrett's esophagus.

PMID- 15990049
TI  - Endoscopic ultrasound for luminal malignancies.
AB  - Luminal gastrointestinal (GI) tract cancers are responsible for substantial
      morbidity and mortality. Since the first pairing of ultrasonography with
      endoscopy in 1980, technologic advances and the increased availability of trained
      endosonographers have propelled endoscopic ultrasonography (EUS) to the forefront
      of luminal GI cancer staging. In this article we discuss the role of EUS for
      evaluating luminal GI cancers.

PMID- 15990050
TI  - Endoscopic mucosal resection: treatment of neoplasia.
AB  - Techniques of endoscopic mucosal resection (EMR) can dramatically improve the
      ability to diagnose and treat superficial lesions in the gastrointestinal (GI)
      tract. Early cancers, submucosal tumors, and sessile polyps can be safely and
      completely removed in a single procedure, with long-term outcome results
      comparable to surgery. This is accomplished with a minimum cost, morbidity, and
      mortality and with little or no impact on the quality of life of patients. This
      article provides an overview of the techniques, indications, and outcomes of EMR
      in the management of GI malignancy.

PMID- 15990051
TI  - Endoscopic approach to gastrointestinal stromal tumors.
AB  - Unrevealing CT scans and ambiguous surveillance endoscopies fuel rising
      frustration for patient and physician. Several recent developments have added
      considerably to our understanding of submucosal masses and the stromal cell
      tumors often lurking within them.

PMID- 15990052
TI  - Endoluminal palliation.
AB  - Endoluminal palliation involves the application of endoscopic techniques or
      devices to relieve the symptoms of malignant gastrointestinal obstruction. This
      is most often achieved with the use of self-expandable metal stents (SEMS). SEMS
      can be deployed as far distally or proximally in the gastrointestinal tract as
      the reach of an adult colonoscope. This article outlines the use of endoscopic
      techniques to provide endoluminal palliation.

PMID- 15990053
TI  - Approach to cystic pancreatic lesions.
AB  - Cystic neoplasms of the pancreas represent the best example of a malignant
      precursor in the pancreas. There are many parallels between pancreatic cystic
      neoplasms and the colon polyp-cancer sequence. In the past, cystic neoplasms of
      the pancreas were thought to be relatively rare, composing less than 10% of
      cancers of the pancreas. With the greater use of cross-sectional imaging, an
      increasing number of these neoplasms are being seen.

PMID- 15990054
TI  - The role of endoscopic ultrasonography in the evaluation of pancreatico-biliary
      cancer.
AB  - Accurate staging of pancreatico-biliary cancer is essential for surgical planning
      and for identification of locally advanced and metastatic disease that is
      incurable by surgery. The complex regional anatomy of the pancreatico-biliary
      system makes histologic diagnosis of malignancy at this region difficult. The
      ability to position the endoscopic ultrasound transducer at endoscopy in direct
      proximity to the pancreas and the bile duct, combined with the use of fine-needle
      aspiration, enables accurate preoperative staging of cancer, especially cancer
      too small to be characterized by CT or MRI. Endoscopic ultrasonography (EUS)
      identifies patients unlikely to be cured by surgery due to vascular invasion or
      regional nodal metastasis, thereby limiting procedure-related morbidity and
      mortality. This article focuses on the utility and recent advances of EUS in the
      evaluation of pancreatico-biliary cancer.

PMID- 15990055
TI  - Endoscopic palliation of pancreaticobiliary malignancies.
AB  - The palliation of pancreaticobiliary malignancies has changed over the last two
      decades. With the development of biliary stents, minimally invasive procedures
      have replaced surgical techniques. Endoscopically placed stents remain the
      mainstay for the palliative treatment of malignant biliary obstruction from
      unresectable pancreaticobiliary tumors. Further improvements in stent designs and
      advances in other endoscopic technologies are expected, and these should expand
      the role of minimally invasive palliation. This article reviews the current and
      anticipated roles of endoscopic techniques in the palliation of
      pancreaticobiliary malignancies.

PMID- 15990056
TI  - Screening and surveillance of colorectal cancer.
AB  - Although colorectal cancer (CRC) is the second leading cause of cancer deaths in
      the United States, it is preventable. Screening modalities include fecal occult
      blood testing, flexible sigmoidoscopy, double-contrast barium enema, and
      colonoscopy. Colonoscopy allows effective detection and removal of precursor
      adenomatous polyps and is the dominant CRC screening modality. Emerging
      technologies include CT and MR colonography and fecal DNA tests. Effective and
      cost-effective surveillance after polypectomy and curative CRC resection requires
      balancing the protective effect of polypectomy while maximizing intervals between
      examinations; thus, estimation of the risk of recurrence determines the intensity
      of surveillance for individual patients.

PMID- 15990057
TI  - Endoscopic management of familial colonic neoplasia.
AB  - Heredity plays an important causative role in a large percentage of colorectal
      cancers. Clinical recognition of the hereditary polyposis syndromes, hereditary
      nonpolyposis colorectal cancer, and common familial colorectal cancer is
      essential because screening, surveillance, and treatment among affected
      individuals and their family members differs from that recommended for the
      general population. More intensive cancer screening and surveillance is required
      if premature death is to be avoided. Genetic testing is commercially available
      for most of the hereditary colorectal cancer syndromes and can greatly facilitate
      the management of patients if properly undertaken.

PMID- 15990058
TI  - State-of-the-art computed tomographic and magnetic resonance imaging of the
      gastrointestinal system.
AB  - Among the major innovations in radiology of the gastrointestinal (GI) system are
      the replacement of classic invasive diagnostic methods with noninvasive ones and
      the improvement in lesion characterization and staging of pancreatobiliary
      malignancies. Developments in imaging technology have led to many improvements in
      the field of diagnostic GI radiology. With its fast and thin-section scanning
      abilities, multidetector-row CT (MDCT) strengthens the place of CT as the most
      efficient tool to diagnose, characterize, and preoperatively stage pancreatic
      neoplasms. MR cholangiopancreatography has widely replaced endoscopic retrograde
      cholangiopancreatography in the diagnosis and staging of pancreatobiliary
      malignancies. MR imaging, using phased-array or endorectal coils, demonstrates
      local tumor invasion accurately in rectal cancers and thus allows an improved
      surgical planning. Virtual colonoscopy with MDCTs is an efficient screening
      method for colon cancer, and MDCT enterography is becoming the standard imaging
      technique for many small bowel disorders. The continuing developments in CT and
      MR technology will most probably further improve the accuracy of these and other
      imaging applications in the near future.

PMID- 15990059
TI  - Emerging endoscopic techniques in oncology.
AB  - New techniques have expanded the role of endoscopy in the diagnosis, staging,
      therapy, and palliation of malignancies. Three major areas of emerging
      technologies--endoscopic ultrasound (EUS), luminal stent technology, and
      photodynamic therapy (PDT)--are discussed in this article. Although EUS and PDT
      have been used for more than two decades, they have only recently emerged as
      established integral methods in the armamentarium of the gastrointestinal
      endoscopist.

PMID- 15990060
TI  - New frontiers in endoscopic imaging.
AB  - Gastrointestinal (GI) tract malignancies have a tremendous impact on society.
      Colorectal cancer is the second leading cause of cancer death in the United
      States and accounts for 10% of all cancer deaths. Significant research efforts
      are being directed toward using the interaction of light and tissue to detect pre
      cancerous lesions of the GI tract. This article reviews the current status of
      various experimental optical technologies to detect pre-cancerous changes in the
      GI tract and focuses on the clinical applications of these technologies for the
      practicing gastroenterologist.

PMID- 15990061
TI  - Materials for urinary catheters: a review of their history and development in the
      UK.
AB  - The Foley catheter, introduced in the mid-1930s and originally manufactured from
      latex, is still the most commonly used device for the management of urinary
      incontinence (UI). Despite the passage of time, there are still problems
      associated with the use of these devices. It is currently estimated that the
      management and treatment of UI costs the UK National Health Service (NHS) in the
      order of 500 million pound per annum. Faced with the known demographic changes in
      the adult population these costs will continue to rise for the foreseeable
      future. This review examines the range of materials currently used to manufacture
      Foley catheters from both latex and silicone. It outlines the common problems
      associated with their clinical use-infection, encrustation and blockage. The main
      changes that have been made to the materials employed in response to these
      problems are analysed. In the first instance the use of controlled release glass
      and slow release polymers to introduce disinfectants and antibacterial agents is
      considered. Attempts to alter surface properties by using coatings based on
      silver, polytetrafluoroethylene (PTFE), hydrogels and silicone are then
      described. It can be seen that despite these approaches, problems remain with the
      design and materials currently used to manufacture catheters. The review
      concludes that changes to the materials currently used for the manufacture of
      commercially available catheters could potentially alleviate many of the existing
      problems. However, standards need to be developed in order to enable direct
      comparison of the mechanical and physical properties of existing and potential
      catheter designs to ensure their effective function in-service.

PMID- 15990062
TI  - Wall pressure gradient in normal left coronary artery tree.
AB  - The three-dimensional wall pressure gradient (WPG) of the normal human left
      coronary artery (LCA) tree is quantitatively analysed. A model LCA tree, based on
      averaged human data set extracted from angiographies was adopted for finite
      element analysis. The LCA tree includes the left main coronary artery (LMCA), the
      left anterior descending (LAD), the left circumflex artery (LCxA) and their major
      branches. The WPG is calculated using 44,452 nodes throughout the tree extension.
      The governing flow equations were solved using a validated numerical code. WPG as
      well as wall shear stress gradient (WSSG) were calculated at all available
      bifurcation regions. In proximal LCA tree regions where atherosclerosis
      frequently occurs, low WPG appears. At distal segments, WPG increases
      substantially due to increased velocity resulted from increased vessel tapering.
      Low WPG occurs at bifurcations in regions opposite the apexes, which are anatomic
      sites predisposed for atherosclerotic development. Endothelial cells respond to
      the combined effects of locally low WPG and low WSSG and provide a mechanism
      promoting atherosclerosis. This computational work determines probably for the
      first time the topography of the WPG in the normal human LCA tree. Spatial WPG
      differentiation indicates that locally low values of this physical parameter
      probably correlate to atherosclerosis localization.

PMID- 15990063
TI  - Investigation of the effects of ischemic preconditioning on the HRV response to
      transient global ischemia using linear and nonlinear methods.
AB  - Ischemic preconditioning (IP) has been used as a strategy to prevent cell death
      in various organs, including the brain and the heart. Investigation of the
      effects of ischemic preconditioning mostly employed models with reduced
      complexity, such as cell cultures, tissue slices or perfused organ preparations.
      Although such models can provide valuable insight into the protective mechanism
      of preconditioning, the functional (re)organization of the control mechanisms at
      the level of the living organism cannot be assessed. The purpose of the present
      animal model study was to evaluate the effect of global ischemic preconditioning
      on the heart rate variability (HRV) response to the asphyxia insult. The data
      consisted of 4 h RR interval measurements recorded in five preconditioned and
      five non-preconditioned Wistar rats. Using linear (time and frequency domain) and
      nonlinear (approximate entropy and parameters of Poincare plots) measures, we
      evaluated the dynamic time course of the HRV response to the asphyxia insult and
      the effect of preconditioning on the autonomic neurocardiac control. Both the
      linear and nonlinear parameters indicate a faster recovery of the baseline HRV
      corresponding to the preconditioned groups, though only the spectral analysis
      identifies a statistically significant difference between the two groups. For the
      preconditioned group, at about 90 min after the asphyxic insult, the autonomic
      neural balance (measured by LF/HF ratio) appears fully recovered. The small
      variation of the rest of the parameters indicates the necessity of further
      investigation including the design of a larger study with a higher statistical
      power. Our results show for the first time that global ischemic preconditioning
      influences the HRV response to the asphyxia injury. The neuroprotective effect of
      preconditioning translates into a faster recovery of the basal HRV and the
      autonomic modulation of the heart.

PMID- 15990064
TI  - Anatomical hip model for the mechanical testing of hip protectors.
AB  - An anatomical hip model has been developed to simulate the impact load on the hip
      of a falling person wearing a hip protector. The hip consists of an artificial
      pelvis made of aluminium, linked by a ball-and-socket joint to an anatomically
      shaped steel femur (thigh bone). The femur is embedded in silicone material with
      a hip-shaped surface to allow realistic positioning of the protectors with
      accessory underwear. Additionally, the silicone simulates the damping and load
      dispersal effect of soft tissue. A triaxial load sensor is integrated in the neck
      of the femur to measure the axial and cross-sectional force components in
      response to external impact forces on the hip. The performance of the hip model
      was investigated in drop tests and validated against biomechanical data. In a
      first series of measurements, the shock absorption of 10 different hip
      protectors, including both energy-absorbing and energy-shunting systems, was
      analysed. To determine the importance of hip protector placement, each protector
      was tested in the correct anatomical alignment over the hip and anteriorly
      displaced by 3 cm. Considerable differences were found between individual hip
      protectors in their effectiveness to reduce impact forces on the femur. Position
      of the hip protector also influenced the forces applied to the femur.

PMID- 15990065
TI  - Failure analysis of broken pedicle screws on spinal instrumentation.
AB  - Revised spinal surgery is needed when there is a broken pedicle screw in the
      patient. This study investigated the pedicle screw breakage by conducting
      retrieval analyses of broken pedicle screws from 16 patients clinically and by
      performing stress analyses in the posterolateral fusion computationally using
      finite element (FE) models. Fracture surface of screws was studied by scanning
      electron microscope (SEM). The FE model of the posterolateral fusion with the
      screw showed that screws on the caudal side had larger axial stress than those on
      the cephalic side, supporting the clinical findings that 75% of the patients had
      the screw breakage on the caudal side. SEM fractography showed that all broken
      screws exhibited beach marks or striations on the fractured surface, indicating
      fatigue failure. Screws of patients with spinal fracture showed fatigue
      striations and final ductile fracture around the edge. Among the 16 patients who
      had broken pedicle screws 69% of them achieved bone union in the bone graft,
      showing that bone union in the bone graft did not warrant the prevention of screw
      breakage.

PMID- 15990066
TI  - A description of an accelerometer-based mobility monitoring technique.
AB  - Accurate monitoring of the mobility status of older adults, over the long-term,
      is important in rehabilitation medicine, as regular physical activity is central
      to maintaining both physical and mental health, as well as evaluating quality of
      life. This technical note describes an accelerometer-based mobility monitoring
      technique, which can distinguish between static and dynamic activities and can
      detect the basic postures of sitting, standing and lying. The technique allows
      thresholds for these postures to be set and two different posture threshold
      methods are described: mid-point and "best estimate". Preliminary results from
      using these methods are presented. This preliminary evaluation of the technique
      was carried out over the long-term (>29 h) in an uncontrolled environment and the
      method used to carry out the evaluation is described in detail. The two different
      posture thresholding methods were tested on long-term mobility data from one
      older adult subject. The subject did not have to follow a specific activity
      protocol during the recording period (4 days) and was shadowed by an observer in
      order to evaluate the accuracy of this technique. The monitoring hardware
      consisted of two accelerometer devices, one on the trunk and the other on the
      thigh and a pocket-sized ambulatory data-logger. Applying 'best estimate'
      thresholding, as opposed to mid-point thresholding, improved sitting detection
      accuracy by 18%, to 93% and lying detection accuracy by 5%, to 84%. Thus, based
      on these preliminary data, an accurate mobility monitoring system for older
      adults is described and it was observed that the actual posture threshold limits
      applied have a high impact on the mobility monitoring system's accuracy and are
      particularly important for accurately detecting postures when used over the long
      term, in an uncontrolled environment.

PMID- 15990067
TI  - Technical note: validation of a motion analysis system for measuring the relative
      motion of the intermediate component of a tripolar total hip arthroplasty
      prosthesis.
AB  - Tripolar total hip arthroplasty (THA) prosthesis had been suggested as a method
      to reduce the occurrence of hip dislocation and microseparation. Precisely
      measuring the motion of the intermediate component in vitro would provide
      fundamental knowledge for understanding its mechanism. The present study
      validates the accuracy and repeatability of a three-dimensional motion analysis
      system to quantitatively measure the relative motion of the intermediate
      component of tripolar total hip arthroplasty prostheses. Static and dynamic
      validations of the system were made by comparing the measurement to that of a
      potentiometer. Differences between the mean system-calculated angle and the angle
      measured by the potentiometer were within +/-1 degrees . The mean within-trial
      variability was less than 1 degrees . The mean slope was 0.9-1.02 for different
      angular velocities. The dynamic noise was within 1 degrees . The system was then
      applied to measure the relative motion of an eccentric THA prosthesis. The study
      shows that this motion analysis system provides an accurate and practical method
      for measuring the relative motion of the tripolar THA prosthesis in vitro, a
      necessary first step towards the understanding of its in vivo kinematics.

PMID- 15990068
TI  - A portable vibrator for muscle performance enhancement by means of direct muscle
      tendon stimulation.
AB  - Combining vibration stimulation with conventional resistance training has gained
      in popularity. However, no portable vibrator capable of directly stimulating
      muscle tendon appears to feature in the literature. The aim of this study was the
      development of such a unit. The unit developed makes use of a rotating eccentric
      mass system to produce desired amplitude and frequency range capable of
      investigating the diverse vibration characteristics used in previous research
      studies. The effects of strapping force, joint angle and day-to-day repeatability
      on these vibration characteristics were investigated. In addition, muscle
      electromyography (EMG) activity was subsequently used to identify the optimum
      vibration amplitude and frequency. Finally, the repeatability of these EMG
      responses and effect of joint angle were examined. The unit was able to produce
      desired vibration characteristics (amplitude: 0.2-2 mm; frequency: 30-200 Hz).
      Test day, strapping force and joint angle had no significant effect on these
      characteristics (p>0.05). Both amplitudes (0.5 and 1.2 mm) and all three
      frequencies (30, 65 and 100 Hz) tested, significantly enhanced EMG activity
      (p<0.05), with 1.2 mm and both 65 and 100 Hz resulting in significantly greater
      enhancements (p<0.05). Joint angle had no significant effect on these EMG results
      (p>0.05). The day-to-day repeatability of EMG response was shown to be high
      (r=0.76-0.90).

PMID- 15990069
TI  - An instrument for the non-invasive assessment of lip function during speech.
AB  - This paper describes the development of an instrument using infrared light as a
      non-invasive means of detecting lip opening, the extent of the opening and also
      the forward protrusion and backward movement of the lips during speech. The
      design criteria were to build a simple stand alone means of assessing lip
      function, which could also link to the group's commercially available Super Nasal
      Oral Ratiometry System (SNORS+). SNORS+ allows objective assessment of the
      function and co-ordination of key articulators, with lip function previously
      monitored using a video camera. Synchronised tests were carried out using the new
      Lip Function Monitor and the video camera simultaneously, in order to verify that
      the signals produced related directly to the activity of the mouth. A small trial
      was then conducted to show that the system provides reproducible results
      throughout a range of 'normal' subjects. These subjects were of different gender
      and race to create a sample group within which there was a variety of lip sizes
      and face shapes. Technical aspects of the instrument and trial results are
      presented here. These suggest that the simple visual output and feedback of the
      instrument will prove useful in the assessment and management of speech
      disorders.

PMID- 15990070
TI  - Effect of different inertial parameter sets on joint moment calculation during
      stair ascending and descending.
AB  - The reliability of internal joint moment calculation in gait analysis during
      daily living activities is fundamental for clinical decisions based on joint
      function. This calculation, obtained by means of the inverse dynamics, depends on
      several modelling factors, such as assumptions on the segments and on the
      relevant joints constituting the kinematic chain. In this study, the effect of
      five different sets of inertial parameters on three-dimensional calculation of
      lower limb joint moments was investigated during the stair ascending and
      descending of 10 young subjects. The lower limb was represented as a chain of
      three rigid segments: foot, shank and thigh. The inertial parameters sets were
      taken from the literature. The root mean square value over the step cycle of the
      difference between joint moments calculated at the lower limb with different
      inertial parameter sets expressed in percentage of their corresponding range was
      computed. The results showed small differences between ex vivo and in vivo data,
      between data from different populations and among different modality of inertial
      parameters acquisition. The root mean square value was negligible at the ankle
      and increased as moving proximally among the joints: the maximum was 21.8% in the
      internal/external rotation moment at the hip. In order to achieve accurate
      estimate of lower limb joint moments other factors should be investigated rather
      than optimal inertial parameter set.

PMID- 15990071
TI  - Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset
      (subphenotype) of lupus erythematosus defined by characteristic cutaneous,
      pathological, immunological, and genetic findings.
AB  - Subacute cutaneous lupus erythematosus (SCLE) represents a widespread,
      photosensitive, nonscarring, nonindurated form of lupus erythematosus (LE)
      specific skin disease. SCLE lesions are associated with a distinctive
      immunogenetic background including the production of Ro/SS-A autoantibodies.
      Individuals who have SCLE skin lesions as a component of their presenting
      illnesses represent a distinctive subset (subphenotype) of LE that enjoys a good
      prognosis with respect to life-threatening systemic manifestations of LE. SCLE
      skin lesions can be triggered by a number of different drugs the majority of
      which are capable of producing photosensitivity drug reactions in nonlupus
      patients. Single agent or combination aminoquinoline antimalarial therapy will
      suffice for 75% of SCLE patients. The remaining 25% will require other forms of
      systemic antiinflammatory therapy (e.g., diaminodipenylsulfone (Dapsone),
      thalidomide) or systemic immunosuppressive-immunomodulatory therapy. The
      etiopathogenesis of SCLE skin lesions is thought to result from four sequential
      stages: (1) inheritance of susceptibility genes (HLA 8.1 ancestral haplotype [C2,
      C4 deficiency, TNF-alpha-308A polymorphism], C1q deficiency); (2) loss of
      tolerance/induction of autoimmunity (ultraviolet light, photosensitizing
      drugs/chemicals, cigarette smoking, infection, psychological stress); (3)
      expansion/maturation of autoimmune responses (high levels of autoantibodies
      (Ro/SS-A), immune complexes, autoreactive T-cells); and (4) tissue injury/disease
      induction resulting from various autoimmune effector mechanisms (e.g., direct T
      cell-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity).

PMID- 15990072
TI  - Intravenous immunoglobulins in autoimmune- or parvovirus B19-mediated pure red
      cell aplasia.
AB  - Pure red-cell aplasia (PRCA) is defined as the absence of mature erythroid
      precursors in a bone marrow that otherwise exhibit normal cellularity. Acquired
      PRCA may occur in association with neoplasms (such as lymphoproliferative
      disorders), thymoma, autoimmune disorders, pregnancy, or as a consequence of
      chronic human parvovirus B19 (B19) infection in an immunologically incompetent
      host. PRCA may also develop after exposure to drugs (erythropoietin or
      tacrolimus). PRCA of autoimmune origin was first treated successfully with
      intravenous immunoglobulins (IVIg) more than 20 years ago. Since then, B19
      associated PRCA in solid-organ transplant recipients and in human
      immunodeficiency virus (HIV)-infected patients has also been successfully treated
      with IVIg. Routine maintenance therapy is probably not indicated in HIV-infected
      patients with CD4+ counts above 300/microL, whereas repeated infusions might be
      necessary if CD4+ count is below 80.

PMID- 15990073
TI  - Organic mercury compounds and autoimmunity.
AB  - Based on in vitro studies and short-term in vivo studies, all mercurials were for
      a long time considered as prototypic immunosuppressive substances. Recent studies
      have confirmed that organic mercurials such as methyl mercury (MeHg) and ethyl
      mercury (EtHg) are much more potent immunosuppressors than inorganic mercury
      (Hg). However, Hg interacts with the immune system in the presence of a
      susceptible genotype to cause immunostimulation, antinucleolar antibodies
      targeting fibrillarin, and systemic immune-complex (IC) deposits, a syndrome
      called Hg-induced autoimmunity (HgIA). Recent studies in mice with a susceptible
      genotype has revealed that the immunosuppressive effect of MeHg and EtHg will
      within 1-3 weeks be superseded by immunostimulation causing an HgIA-like
      syndrome. At equimolar doses of Hg, MeHg has the weakest immunostimulating,
      autoimmunogen, and IC-inducing effect, while the effect of thimerosal is similar
      to that of inorganic mercury. The immunosuppression is caused by the organic
      mercurials per se. Since they undergo rapid transformation to inorganic Hg,
      studies are being undertaken to delineate the importance of the organic
      substances per se and the newly formed inorganic Hg for induction of
      autoimmunity.

PMID- 15990074
TI  - Clinical manifestations correlated to the prevalence of autoantibodies in a large
      (n=321) cohort of patients with primary Sjogren's syndrome: a comparison of
      patients initially diagnosed according to the Copenhagen classification criteria
      with the American-European consensus criteria.
AB  - In this study we imposed the recently described American-European consensus
      criteria for primary Sjogren's syndrome (pSS) on a large cohort of patients
      originally classified according to the Copenhagen set of criteria. Of the 321
      patients fulfilling the Copenhagen criteria, 205 conformed to the Consensus
      criteria. When comparing clinical manifestations and laboratory findings between
      the two groups defined by different standards we found only small variations.
      Thus, the consequence of using the Consensus criteria in daily clinical practice
      will lead to the exclusion of a considerable proportion of patients with
      classical features of pSS. The main reason for this discrepancy is probably the
      absolute requirement of a positive test for anti-Ro/La or a characteristic
      lymphocytic infiltration in the labial gland biopsy. The sensitivity and
      specificity of testing for autoantibodies to Ro-52, Ro-60, and La were calculated
      for each set of criteria. Antibodies to La but not to Ro-52 or Ro-60 were
      strongly correlated to internal organ (kidney, lung, liver) dysfunction in pSS
      (OR 6; 95% CI 3-12), p<0.0001. Although presence of ANA was slightly more
      prevalent among patients with internal organ involvement it did not reach
      statistical significance. The fine speckled ANA pattern was most often found
      followed by the homogeneous and centromere pattern. Individual ANA patterns did
      not correlate with any particular organ manifestation.

PMID- 15990075
TI  - Immunology and genetics of induced systemic autoimmunity.
AB  - Systemic lupus erythematosus is a multigenic disorder of unknown etiology. To
      investigate the role of specific genes in lupus, we have examined the effects of
      single gene deletions on mercury-induced autoimmunity. Deficiency of certain
      genes abrogated induction of autoimmunity, while absence of others had little
      effect. The most interesting observations were obtained with genes related to
      interferon-gamma. Genes involved in upregulation of IFN-gamma expression did not
      significantly influence autoimmunity whereas absence of IFN-gamma or IFN-gamma
      receptor led to greatly reduced autoantibody responses and immunopathology.
      Absence of IRF-1, a gene expressed in response to IFN-gamma, resulted in
      selective retention of anti-chromatin autoantibodies demonstrating that specific
      defects in signaling pathways and gene expression subsequent to IFN-gamma/IFN
      gamma receptor interaction influence specific disease parameters. These studies
      show that single gene deletions can have various outcomes ranging from no effect,
      suppression of one or more features of disease, to suppression of all features of
      disease, and that all three outcomes can be observed in the IFN-gamma pathway.
      IFN-gamma influences the expression and function of other lupus relevant genes
      such as IL-6 and beta2microglobulin, therefore the effects of these gene
      deletions on disease expression may also reflect responses downstream of IFN
      gamma function.

PMID- 15990076
TI  - Anti-beta 2-glycoprotein-I antibodies in scFv format.
AB  - Phage display was introduced almost 20 years ago. It has been used to produce
      large amounts of diverse proteins, to analyze protein-ligand interactions, to
      improve the affinity of proteins for their binding receptors, and to characterize
      antibody binding sites. The recombinant version of the antibody Fv is termed
      single-chain variable fragment (scFv). Many large phage libraries have been
      developed that have yielded antibodies to several hundred antigens, but only 5
      human anti-beta2-glycoprotein-I and three anti-prothrombin antibodies in scFV
      have been so far characterized. Antibodies to beta2GP-I thus generated show 92
      94% homology with their nearest germ line genes. Their mutations frequently
      appear to be independent of antigen. Two anti-prothrombin antibodies show strong
      crossreactivity with beta2GP-I. Four mouse anti-beta2GP-I scFV show less binding
      properties than their original counterparts, but had the same capacity of
      inducing experimental antiphospholipid syndrome. This pathogenicity appears to
      reside in the V(H)DJ(H)C(H) region of the scFv since the V(H)DJ(H)C(H) regions of
      pathogenic scFV combined with irrelevant V(L) J(L)C(L) regions retained their
      pathogenicity while the opposite failed to do so.

PMID- 15990077
TI  - Clinical manifestations of cutaneous lupus erythematosus.
AB  - The skin findings seen in lupus erythematosus can present with either lupus
      specific or lupus-nonspecific findings, with lupus-specific skin disease showing
      findings histopathologically distinct for cutaneous lupus erythematosus. Lupus
      specific skin diseases include chronic cutaneous, subacute cutaneous, and acute
      cutaneous lupus erythematosus. The types of skin lesions in each group are
      clinically distinct and recognizing the specific subsets helps in prognosticating
      the likelihood of underlying systemic lupus. A number of medications are
      associated with cutaneous lupus, in particular with subacute cutaneous lupus
      erythematosus. Lupus nonspecific skin lesions are not histopathologically
      distinct for cutaneous lupus and/or may be seen as a feature of another disease
      process. Nonspecific disease-related skin lesions are frequently seen in patients
      with SLE, usually in the active phase of the disease. The current ACR
      classification criteria for SLE include four somewhat overlapping dermatologic
      criteria, butterfly rash, discoid lupus, photosensitivity, and oral ulcers and
      thus patients can be classified as having SLE with only skin manifestations.

PMID- 15990078
TI  - Avidity of anti-beta-2-glycoprotein I antibodies.
AB  - The terms affinity and avidity are often used indiscriminately, despite clearly
      differing. Since affinity refers to monovalent binding of antibodies to a
      monovalent epitope, the majority of data on the binding of anti-beta2
      glycoprotein I antibodies (anti-beta2-GPI) characterized their avidity rather
      than affinity. Anti-beta2-GPI were generally believed to be of low avidity, but
      heterogeneous avidity of patients' IgG anti-beta2-GPI has been demonstrated. High
      avidity anti-beta2-GPI monoclonals were reported to possess higher pathogenicity
      than low avidity anti-beta2-GPI. Polyclonal high avidity anti-beta2-GPI were
      found to be more common in patients with antiphospholipid syndrome (APS) and
      associated with thrombosis. Some conformational changes of beta2-GPI are required
      for the binding of polyclonal anti-beta2-GPI to the antigen: neither high density
      of the antigen nor high avidity of the anti-beta2-GPI alone is sufficient for the
      recognition. Avidity of anti-beta2-GPI should be considered in any attempt of
      inter-laboratory standardisation and/or evaluation of anti-beta2-GPI enzyme
      linked immunosorbent assay (ELISA).

PMID- 15990079
TI  - Current trends in drug-induced autoimmunity.
AB  - There are several hypotheses for the mechanism of drug-induced autoimmunity. It
      could be looked upon as an inappropriate activation of the immune system. One
      hypothesis is that drugs can inhibit DNA methylation leading to the activation of
      T cells. Another is that reactive metabolites can interfere with tolerance. Still
      other hypotheses focus on activation of antigen presenting cells (APCs).
      Monocytes can form chemically reactive metabolites and such metabolites could
      lead to their activation. One type of interaction between APCs and T cells
      involves the reversible formation of an imine bond between an amine on T cells
      and an aldehyde on the APCs. Several drugs, such as penicillamine and
      hydralazine, react irreversibly with aldehydes, and they are also associated with
      a high incidence of drug-induced lupus. This type of interaction may lead to
      activation of APCs and the induction of autoimmunity. However, there is no clear
      evidence to suggest that there is one simple mechanism by which drugs induce
      autoimmunity, and it is likely that several mechanisms may be involved and they
      may be different for different drugs.

PMID- 15990080
TI  - T cell immunity in autoimmune hepatitis.
AB  - T cells play a central role in the immunopathogenesis of AIH. Until recently CD4+
      T cells were thought to be critical for disease development, increasing evidence
      has shown that CD8+ T and gammadelta T cells also play a significant role. The
      predisposition of certain HLA genotypes to AIH as well as the clonal expansion of
      a limited number of T cell receptors suggests that the presentation of a self
      antigen or a molecular mimic may be responsible for the initiation of the immune
      response. Given the association of AIH with viral hepatitis, it is thought that
      the loss of tolerance begins with an infection of hepatocytes and subsequent
      cytolysis by CD8+ T cells. The presentation of self-antigens or molecular mimics
      leads to activation and clonal expansion of T cells; this process may be
      increased by impaired regulatory T cells and a defect in apoptosis. Ultimately T
      cells initiate B cell production of autoantibodies, proinflammatory cytokines and
      finally hepatocyte cytotoxicity.

PMID- 15990082
TI  - Acetate peel technique: a rapid way of preparing sequential surface replicas of
      dental hard tissues for microscopic examination.
AB  - OBJECTIVE: In order to study dental structures in three-dimensional views,
      sequential microscopic sections are needed. Routine thin-sectioning needs
      equipment, it is time-consuming, expensive and cause sample wastage during
      sectioning. The acetate peel technique used for microscopic examinations of
      carbonate rocks and fossils was modified and successfully adapted for teeth.
      DESIGN: A human tooth was embedded in resin block; the surface to be peeled was
      ground and polished with carborundum powder on a glass plate using water. The
      polished surface was etched, washed, and dried. The dry surface was flooded with
      acetone and a piece of acetate film was placed over it. As the acetone
      evaporated, the film settled down to take the shape of micro relief produced by
      etching. The film dried in 10--15 min. It was pulled off the surface and mounted
      between two glass slides for examination under microscope. RESULTS: This
      technique enabled making numerous sequential surface replicas (peels) from a
      tooth, especially from fully mineralised enamel without routine decalcifying,
      dehydrating, sawing, and mounting processes. CONCLUSIONS: The results obtained
      with the stained peels, showed that this technique is an efficient way to study
      gross and fine structures of etched dental hard tissues surfaces and restoration
      cavity marginal integrity with three-dimensional detail.

PMID- 15990081
TI  - The safety and efficacy of travoprost 0.004%/timolol 0.5% fixed combination
      ophthalmic solution.
AB  - PURPOSE: To compare the safety and intraocular pressure (IOP)-lowering efficacy
      of travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution
      (Trav/Tim) to its components travoprost 0.004% ophthalmic solution, TRAVATAN,
      (Trav) and timolol 0.5% ophthalmic solution (Tim) in patients with open-angle
      glaucoma or ocular hypertension. DESIGN: Randomized multicenter, double-masked,
      active-controlled, parallel group study. METHODS: Two hundred sixty-three
      patients with open-angle glaucoma or ocular hypertension were randomized to
      receive Trav/Tim once daily AM (and vehicle PM), Trav once daily PM (and vehicle
      AM), or Tim twice daily (AM and PM). Efficacy and safety were compared across
      treatment groups over 3 months. RESULTS: Trav/Tim produced a mean IOP decrease
      from baseline of 1.9 mm Hg to 3.3 mm Hg more than Tim, with a significant
      decrease in mean IOP at each of the nine study visits (P < or = .003). Trav/Tim
      decreased mean IOP by 0.9 mm Hg to 2.4 mm Hg more than Trav, with a significant
      decrease in mean IOP at seven of the nine study visits (P < or = .05). The
      adverse event profile for Trav/Tim was comparable to Trav or Tim alone.
      CONCLUSIONS: Over the 3 months of treatment, Trav/Tim produced clinically
      relevant IOP reductions in patients with open-angle glaucoma or ocular
      hypertension that were greater than those produced by either Trav or Tim alone.
      The clinical results that Trav/Tim was safe and well tolerated with an incidence
      of adverse events was comparable to the results of Trav or Tim alone. Trav/Tim
      provides both more effective IOP reduction than its components and the benefits
      of once-daily dosing.

PMID- 15990083
TI  - Subgingival distribution of Campylobacter rectus and Tannerella forsythensis in
      healthy children with primary dentition.
AB  - OBJECTIVE: It is important to know how many subgingival plaque samples should be
      assayed from a child to ascertain infection with a periodontal pathogen. Plaque
      samples from several sites may fail to detect some important bacteria if only a
      limited number of gingival sites are sampled. The purpose of this study was to
      evaluate the detection of periodontal pathogens in a large number of subgingival
      sites in the same children in order to determine the number of samples necessary.
      METHODS: Ten children, aged 4-6 years, with complete primary dentition were
      enrolled in this study. Plaque samples from the mesio-buccal aspect of each
      erupted tooth were first collected by gently inserting a sterile paper point for
      10s. Purified genomic DNA from all plaque samples was prepared for polymerase
      chain reaction. The primers for species-specific 16S ribosomal RNA sequence were
      selected as the target sequence. Standard strains of Campylobacter rectus and
      Tannerella forsythensis (formerly Bacteroides forsythus) were used as control
      strains. RESULTS: All subjects were found positive for C. rectus and T.
      forsythensis with the mean of positive sites at 17.6 +/- 2.4 (range: 12-20 sites)
      for C. rectus and 9.3 +/- 5.0 (range: 1-19) for T. forsythensis. The mean number
      of positive sites was 1.7 +/- 0.8 for C. rectus and 6.5 +/- 4.9 for T.
      forsythensis, with a confidence ratio of 95%. CONCLUSIONS: We concluded that two
      or more random sites for C. rectus and seven or more random sites for T.
      forsythensis from children to detect those bacteria at 95% probability.

PMID- 15990085
TI  - Thiazolidinediones inhibit TNFalpha induction of PAI-1 independent of PPARgamma
      activation.
AB  - Increased plasminogen activator inhibitor type 1 (PAI-1) levels are observed in
      endothelial cells stimulated by tumour necrosis factor alpha (TNFalpha).
      Thiazolidinediones (TZDs) may inhibit elevated endothelial cell PAI-1 accounting,
      in part, for the putative atheroprotective effects of TZDs. In an endothelial
      cell line, Rosiglitazone (RG) and Pioglitazone (PG) inhibited induction of PAI-1
      by TNFalpha. The specific peroxisome proliferator-activated receptor gamma
      (PPARgamma) inhibitor, SR-202, failed to modulate this effect. RG also inhibited
      the effect of TNFalpha on a reporter gene construct harbouring the proximal PAI-1
      promoter and PAI-1 mRNA in cells co-transfected with a dominant-negative
      PPARgamma construct. RG and PG attenuated TNFalpha-mediated induction of trans
      acting factor(s) Nur77/Nurr1 and binding of nuclear proteins (NP) to the cis
      acting element (NBRE). SR-202 failed to modulate these effects. The observations
      suggest TZDs inhibit TNFalpha-mediated PAI-1 induction independent of inducible
      PPARgamma activation and this may involve in the modulation of Nur77/Nurr1
      expression and NP binding to the PAI-1 NBRE.

PMID- 15990084
TI  - Interaction of a pseudosubstrate peptide of protein kinase C and its
      myristoylated form with lipid vesicles: only the myristoylated form translocates
      into the lipid bilayer.
AB  - Lipopeptides derived from protein kinase C (PKC) pseudosubstrates have the
      ability to cross the plasma membrane in cells and modulate the activity of PKC in
      the cytoplasm. Myristoylation or palmitoylation appears to promote translocation
      across membranes, as the non-acylated peptides are membrane impermeant. We have
      investigated, by fluorescence spectroscopy, how myristoylation modulates the
      interaction of the PKC pseudosubstrate peptide KSIYRRGARRWRKL with lipid vesicles
      and translocation across the lipid bilayer. Our results indicate that
      myristoylated peptides are intimately associated with lipid vesicles and are not
      peripherally bound. When visualized under a microscope, myristoylation does
      appear to facilitate translocation across the lipid bilayer in multilamellar
      lipid vesicles. Translocation does not involve large-scale destabilization of the
      bilayer structure. Myristoylation promotes translocation into the hydrophobic
      interior of the lipid bilayer even when the non-acylated peptide has only weak
      affinity for membranes and is also only peripherally associated with lipid
      vesicles.

PMID- 15990086
TI  - Human Yip1A specifies the localization of Yif1 to the Golgi apparatus.
AB  - Yip1p and Yif1p are essential for transport from ER to Golgi stack during the
      early secretory pathway in budding yeast. Here, we report the identification and
      characterization of human Yif1. Sequence analysis revealed that human Yif1
      (HsYif1), like most of the other YIP1 protein family members, contains multiple
      transmembrane segments. Double immunofluorescence study revealed co-distribution
      of HsYif1 with Golgi marker such as GS27. To delineate the function of HsYif1, we
      conducted a yeast two-hybrid assay and identified an interaction between human
      HsYif1 and HsYip1A, a homolog of yeast Yip1. In addition, our immunoprecipitation
      pull-down assay validates the interaction between HsYif1 and HsYip1A. Moreover,
      our immunofluorescence study demonstrates the co-distribution of HsYif1 and
      HsYip1A. Significantly, over-expression of mutant HsYip1A-lacked cytosolic region
      disrupts the localization of HsYif1 to the Golgi, suggesting that HsYip1A
      specifies the localization of HsYif1 to the Golgi. Therefore, we conclude that
      human Yip1A interacts with and determines the localization of HsYif1 to the Golgi
      apparatus.

PMID- 15990087
TI  - Extracellular matrix protein 1 interacts with the domain III of fibulin-1C and 1D
      variants through its central tandem repeat 2.
AB  - Extracellular matrix protein 1 (ECM1), a widely expressed glycoprotein, has been
      shown to harbor mutations in lipoid proteinosis (LP), an autosomal recessive
      disorder characterized by profound alterations in the extracellular matrix of
      connective tissue. The biological function of ECM1 and its role in the
      pathomechanisms of LP are unknown. Fibulins comprise a family of extracellular
      matrix components, and the prototype of this family, fibulin-1, is expressed in
      various connective tissues and plays a role in developmental and pathologic
      processes. In this study, we demonstrate that ECM1, and specifically the second
      tandem repeat domain which is alternatively spliced, interacts with the C
      terminal segments of fibulins 1C and 1D splice variants which differ in their C
      terminal domain III. The interactions were detected by yeast two-hybrid genetic
      system and confirmed by co-immunoprecipitations. Kinetics of the binding between
      ECM1 and fibulin-1D, measured by biosensor assay, revealed a K(d) of 5.71 x 10(
      8) M, indicating a strong protein-protein interaction. Since distinct splice
      variants of ECM1 and fibulin-1 have been shown to be co-expressed in tissues
      affected in LP, we propose that altered ECM1/fibulin-1 interactions may play a
      role in the pathogenesis of this disease as well as in a number of processes
      involving the extracellular matrix of connective tissues.

PMID- 15990088
TI  - Expression and characterization of HlyX hemolysin from Leptospira interrogans
      serovar Copenhageni: potentiation of hemolytic activity by LipL32.
AB  - The HlyX, a putative hemolysin identified from the Leptospira genomes, was
      cloned, expressed in Escherichia coli, purified, and its hemolytic activity was
      confirmed. Mouse polyclonal antiserum against the recombinant HlyX recognized
      HlyX-related antigens in a panel of Leptospira species extracts and it was also
      able to abolish the hemolytic activity of HlyX. A mixture of HlyX and LipL32, a
      known hemolysin from Leptospira, induced hemolysis in a synergistic way that was
      fully inhibited by antiserum against either protein. Moreover, sera from patients
      with leptospirosis also recognized the recombinant HlyX, showing that it is
      presented to the host immune system during Leptospira infection.

PMID- 15990089
TI  - Role of 5'-nucleotidase in thiopurine metabolism: enzyme kinetic profile and
      association with thio-GMP levels in patients with acute lymphoblastic leukemia
      during 6-mercaptopurine treatment.
AB  - Thiopurines are used for treatment of several diseases. Cytotoxicity is caused by
      the derived compounds 6-thioguanine nucleotides (TGNs) and methyl-6-thioinosine
      monophosphate (methylthio-IMP). The 6-thiopurine mononucleotides 6-thio-IMP (thio
      IMP), 6-thio-GMP (thio-GMP) and methylthio-IMP can be catabolized by purine 5'
      nucleotidase. It has been shown that the various 5'-nucleotidases are key enzymes
      for (6-thio)-purine metabolism. We aimed to investigate whether the overall 5'
      nucleotidase (5'NT) activity is correlated with the efficacy and toxicity of 6
      thiopurine nucleotides. Substrate affinity of 5'NT for IMP, GMP, AMP, thio-IMP,
      thio-GMP and methylthio-IMP was studied in human lymphocytes. For each of the
      substrates, the pH for optimal overall enzyme activity has been determined at a
      pH range between 6 and 10. At the optimal pH, assays were performed to establish
      Km and Vmax values. Optimal pH values for the various substrates were between 7
      and 8.5. Km values ranged from 33 to 109 microM, Vmax ranged from 3.99 to 19.5
      nmol/10(6) peripheral mononuclear cells (pMNC) h, and Vmax/Km ratios ranged from
      105 to 250. The results did not show a distinct preference of 5'NT activity for
      any of the tested thiopurine nucleotides. The enzyme kinetic studies furthermore
      revealed substrate inhibition by thio-IMP and thio-GMP as a substrate. Inhibition
      by thio-GMP also seems to occur in patients treated with 6-mercaptopurine (6 MP);
      subsequently, this may lead to toxicity in these patients.

PMID- 15990090
TI  - MOM-5 frizzled regulates the distribution of DSH-2 to control C. elegans
      asymmetric neuroblast divisions.
AB  - Asymmetric cell divisions produce all 302 neurons of the C. elegans
      hermaphrodite. Here, we describe a role for a C. elegans Dishevelled homolog, DSH
      2, in an asymmetric neuroblast division. In dsh-2 mutants, neurons normally
      descended from the anterior neuroblast daughter of the ABpl/rpppa blast cell were
      frequently duplicated, while non-neuronal cells produced by the posterior
      daughter cell were often missing. These observations indicate that in the absence
      of dsh-2 function, the posterior daughter cell was transformed into a second
      anterior-like cell. Loss of mom-5, a C. elegans frizzled homolog, produced a
      similar phenotype. We also show that the DSH-2 protein localized to the cell
      cortex in most cells of the embryo. In the absence of MOM-5/Fz, DSH-2 was
      localized to the cytoplasm, suggesting that MOM-5 regulates asymmetric cell
      division by controlling the localization of DSH-2. Although all neurons in C.
      elegans are produced by an invariant pattern of cell divisions, our results
      indicate that cell signaling may contribute to asymmetric neuroblast division
      during embryogenesis.

PMID- 15990091
TI  - Endothelin-1-induced translocation of RhoA is mediated by endothelin ET(A)
      receptors in rat bronchial smooth muscle.
AB  - To clarify the receptor subtype(s) contributing to the RhoA activation by
      endothelin-1 in bronchial smooth muscle, the effects of BQ-123 [cycro(D-Asp-Pro-D
      Val-Leu-D-Trp)], an endothelin ET(A) receptor antagonist, and/or BQ-788 [2,6
      dimethylpiperidinecarbonyl-g-methyl-Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle], an
      endothelin ET(B) receptor antagonist, on the endothelin-1-induced translocation
      of RhoA to plasma membrane were examined. Incubation of rat bronchial smooth
      muscle with endothelin-1 induced a distinct translocation of RhoA to plasma
      membrane, indicating an activation of RhoA by endothelin-1. The endothelin-1
      induced translocation of RhoA was completely blocked by treatment with BQ-123,
      whereas BQ-788 had no effect. Thus, endothelin ET(A) but not ET(B) receptors
      might be involved in the endothelin-1-induced translocation of RhoA in rat
      bronchial smooth muscle.

PMID- 15990092
TI  - Regulatory role of hepatocyte nuclear factor-4alpha on gastric choriocarcinoma
      function.
AB  - Gastric choriocarcinoma is a highly aggressive carcinoma, most probably
      originating from somatic cells in the gastric mucosal layer. We herein
      investigated the regulatory role of hepatocyte nuclear factor (HNF)-4alpha, a
      transcriptional regulator expressed in non-neoplastic and neoplastic gastric
      tissues, on functions of gastric choriocarcinoma cells. HNF-4alpha cDNA was
      stably transfected to a gastric choriocarcinoma cell line, SCH. Alterations in
      SCH cell functions such as histology, ultrastructure, proliferation, production
      of trophoblast-specific proteins, and chemosensitivity to methotrexate (MTX) were
      examined. Neither in vitro and in vivo proliferations nor HLA-G expression
      differed significantly between the mock-transfected and HNF-4alpha-transfected
      SCH cells, while suppressed human chorionic gonadotropin (hCG) secretions,
      increased human placental lactogen (hPL) and carcinoembryonic antigen-related
      cell adhesion molecule 1 (CEACAM1) immunoreactivity, and decreased
      chemosensitivity to MTX were seen in HNF-4alpha-transfected SCH cells. General
      histologic features in xenograft nodules were unaltered, but, ultrastructurally,
      fascicles of paranuclear filaments were significantly more numerous in HNF-4alpha
      transfected SCH cells. These results indicated an HNF-4alpha-rendered functional
      regulation in SCH cells, suggesting a role of transcriptional factors abundant in
      gastric but not in trophoblastic tissues/cells on the functional modulation of
      gastric choriocarcinoma cells.

PMID- 15990093
TI  - Deficient innervation characterizes intestinal strictures in a rat model of
      colitis.
AB  - Intestinal strictures are a common complication of Crohn's disease leading to
      serious consequences. With unknown etiology and cellular composition, strictures
      can be neither prevented nor reversed by current therapeutic strategies, and
      research has been limited by the lack of a well-developed animal model. We
      observed the sporadic occurrence of intestinal strictures at Day 35 in the TNBS
      rat model of colitis, which persisted beyond Day 90. Strictured tissue showed
      fusion, thickening, and disorganization of the smooth muscle layers.
      Immunocytochemistry revealed that all strictures were characterized by deficient
      innervation with a complete loss of intrinsic neurons, and a 92% loss of total
      axons per area. The number of alpha-smooth muscle actin-positive smooth muscle
      cells (SMC) increased in strictures, but immunolabeling showed phenotypic
      modulation of these cells, with the SMC phenotype (desmin-positive, vimentin
      negative) entirely replaced by a myofibroblast phenotype (desmin-negative,
      vimentin-positive). Although cellular structure still predominated in the
      strictured regions, histochemistry showed increased extracellular matrix
      collagen, from 6 +/- 0.9% to 22 +/- 4% of total area. With previous evidence for
      neural loss in colitis, and in vitro studies showing neural regulation of smooth
      muscle cell (SMC) growth, we conclude that the regional loss of innervation may
      initiate tissue re-modeling that is characteristic of stricture formation.

PMID- 15990094
TI  - Molecular interaction of delta-conotoxins with voltage-gated sodium channels.
AB  - Various neurotoxic peptides modulate voltage-gated sodium (Na(V)) channels and
      thereby affect cellular excitability. Delta-conotoxins from predatory cone snails
      slow down inactivation of Na(V) channels, but their interaction site and
      mechanism of channel modulation are unknown. Here, we show that delta-conotoxin
      SVIE from Conus striatus interacts with a conserved hydrophobic triad (YFV) in
      the domain-4 voltage sensor of Na(V) channels. This site overlaps with that of
      the scorpion alpha-toxin Lqh-2, but not with the alpha-like toxin Lqh-3 site.
      Delta-SVIE functionally competes with Lqh-2, but exhibits strong cooperativity
      with Lqh-3, presumably by synergistically trapping the voltage sensor in its "on"
      position.

PMID- 15990095
TI  - Testing polyols' compatibility with Gibbs energy of stabilization of proteins
      under conditions in which they behave as compatible osmolytes.
AB  - It is generally believed that compatible osmolytes stabilize proteins by shifting
      the denaturation equilibrium, native state <--> denatured state toward the left.
      We show here that if osmolytes are compatible with the functional activity of the
      protein at a given pH and temperature, they should not significantly perturb this
      denaturation equilibrium under the same experimental conditions. This conclusion
      was reached from the measurements of the activity parameters (K(m) and k(cat))
      and guanidinium chloride-induced denaturations of lysozyme and ribonuclease-A in
      the presence of five polyols (sorbitol, glycerol, mannitol, xylitol and adonitol)
      at pH 7.0 and 25 degrees C.

PMID- 15990096
TI  - Unfolding and breakdown of insulin in the presence of endogenous thiols.
AB  - Native insulin denatures and unfolds in the presence of thiol catalyst via
      disulfide scrambling (isomerization). It undergoes two transient non-native
      conformational isomers, followed by an irreversible breakdown of the protein to
      form oxidized A- and B-chain. Denaturation and breakdown of native insulin may
      occur under physiological conditions. At 37 degrees C, pH 7.4, and in the
      presence of cysteine (0.2 mM), native insulin decomposes with a pseudo first
      order kinetic of 0.075 h(-1). At 50 degrees C, the rate increases by 5-fold.
      GdnCl and urea induced denaturation of insulin follows the same mechanism. These
      results demonstrate that stability and unfolding pathway of insulin in the
      presence of endogenous thiol differ fundamentally from its reversible
      denaturation observed in the absence of thiol, in which native disulfide bonds of
      insulin were kept intact during the process of denaturation.

PMID- 15990098
TI  - Pre- and post-hatching effects of corticosterone treatment on behavior of the
      domestic chick.
AB  - We investigated the effect of 60 ig of corticosterone administered to domestic
      chicks either before or after hatching on the behavioral response to isolation in
      a novel arena and performance in a task involving the simultaneous identification
      of food and detection of a predator (overhead silhouette of a hawk moving
      overhead). Following release into a novel arena, chicks treated with
      corticosterone at 18 days of incubation emitted more distress vocalizations. In
      contrast, no difference in the number of vocalizations was found between chicks
      treated with corticosterone at day 1 post-hatching and controls. Behavior in the
      home cages was generally similar across treatments, though chicks treated with
      corticosterone at 18 days of incubation slept more than control chicks. While
      searching for grain against a background of pebbles, chicks treated with
      corticosterone at embryonic day 18, but not chicks treated on day 1 post
      hatching, took longer to detect the overhead image of a predator than did
      controls. Corticosterone treatment at both ages increased the rate of pecking at
      grains and pebbles. Our findings support work on other birds indicating that
      corticosterone treatment during incubation influences stress reactivity. The
      impairment in predator detection in chicks treated with corticosterone on day 18
      of incubation appears to be caused by the known effects of corticosterone
      treatment at this age in preventing the development of lateralization of the
      thalamofugal visual projections. This further supports the hypothesis that brain
      lateralization provides an advantage in performing more than one task
      simultaneously.

PMID- 15990097
TI  - Behavioral neuroendocrinology in nontraditional species of mammals: things the
      'knockout' mouse CAN'T tell us.
AB  - The exploration of many of the fundamental features of mammalian behavioral
      neuroendocrinology has benefited greatly throughout the short history of the
      discipline from the study of highly inbred, genetically characterized rodents and
      several other "traditional" exemplars. More recently, the impact of genomic
      variation in the determination of complex neuroendocrine and behavioral systems
      has advanced through the use of single and multiple gene knockouts or knockins.
      In our essay, we argue that the study of nontraditional mammals is an essential
      approach that complements these methodologies by taking advantage of allelic
      variation produced by natural selection. Current and future research will
      continue to exploit these systems to great advantage and will bring new
      techniques developed in more traditional laboratory animals to bear on problems
      that can only be addressed with nontraditional species. We highlight our points
      by discussing advances in our understanding of neuroendocrine and behavioral
      systems in phenomena of widely differing time scales. These examples include
      neuroendocrine variation in the regulation of reproduction across seasons in
      Peromyscus, variation in parental care by biparental male rodents and primates
      within a single infant rearing attempt, and circadian variation in the regulation
      of the substrates underlying mating in diurnal vs. nocturnal rodents. Our essay
      reveals both important divergences in neuroendocrine systems in our
      nontraditional model species, and important commonalities in these systems.

PMID- 15990099
TI  - Differences in corticosterone level due to inter-food interval length:
      implications for schedule-induced polydipsia.
AB  - The purpose of this study was to determine the effects of different food
      reinforcement schedules on plasma corticosterone (CORT), and its possible
      involvement in the acquisition and maintenance of schedule-induced polydipsia
      (SIP). In Experiment 1, three groups of rats were submitted to two different
      fixed-interval (FI) schedules with inter-food intervals of 30 and 120 s, and to a
      massed-feeding presentation for 40 days until SIP was well stabilized. In
      Experiment 2, six groups of rats were exposed to the same schedules, FI 30s and
      FI 120s, and to the massed-feeding condition, but no water bottles were
      presented. CORT levels were determined on Days 3 and 40. Results of Experiment 1
      indicated that FI 30s schedule, but not FI 120s or the massed-feeding condition,
      induces excessive drinking from Day 3. Results in Experiment 2 indicated that
      CORT levels were similar for all the groups on Day 3. However, only animals on
      the FI 30s schedule did increase their CORT levels on Day 40, with no variation
      in the hormone in the other two conditions, FI 120s and massed-feeding
      presentations. The data are discussed in terms of the implications of these
      results for hypotheses of SIP as anxiolitic behavior.

PMID- 15990100
TI  - Genotyping and detection of multiple infections of Toxoplasma gondii using
      Pyrosequencing.
AB  - A Pyrosequencing assay, based on SAG2 gene polymorphisms, was designed for
      genotyping and detection of multiple infections of Toxoplasma gondii. The assay
      was tested on samples spiked with DNA from single and multiple genotypes of T.
      gondii and also on a DNA sample from the brain of a rat with multiple infections.
      To evaluate the comparative efficacy of the assay, identical samples were also
      analysed by PCR-restriction fragment length polymorphism (RFLP) and dideoxy
      sequencing. The Pyrosequencing assay was found to be superior to the two
      conventional techniques. Genotyping and detection of multiple alleles were
      possible after a single PCR assay in duplex format, from both the spiked and
      direct samples. The simplex PCR assay enabled accurate quantification of the
      different alleles in the mix. In comparison, PCR-RFLP and dideoxy sequencing were
      neither able to unequivocally detect multiple genotype infections, nor quantify
      the relative concentrations of the alleles. We conclude that Pyrosequencing
      offers a simple, rapid and efficient means for diagnosis and genotyping of T.
      gondii, as well as detection and quantification of multiple genotype infections
      of T. gondii.

PMID- 15990101
TI  - Spatial and temporal development of chondrocyte-seeded agarose constructs in free
      swelling and dynamically loaded cultures.
AB  - Dynamic deformational loading has been shown to significantly increase the
      development of material properties of chondrocyte-seeded agarose hydrogels,
      however little is known about the spatial development of the material properties
      within these constructs. In this study, a technique that combines video
      microscopy and optimized digital image correlation, was applied to assess the
      spatial development of material properties in tissue-engineered cartilage
      constructs cultured in free-swelling and dynamically-loaded conditions (3h/day, 5
      days/week, and maintained in free-swelling conditions when not being loaded) over
      a 6-week period. Although homogeneous at day 0, both free-swelling and
      dynamically loaded samples progressively developed stiffer outer edges and a
      softer central region. The distribution of GAGs and collagens were shown to mimic
      this profile. These results indicate that although dynamic loading augments the
      development of bulk properties in these samples, possibly by overcoming some of
      the diffusion limitation and nutrient transport issues, the overall profile of
      construct properties in the axial direction remains qualitatively the same as in
      free-swelling culture conditions. Poisson's ratio of these constructs increased
      over time in culture with increased fixed charged density contributed by the
      GAGs, but this increase was significantly less in dynamically loaded samples by
      day 42. Polarized light microscopy of Picrosirius Red labeled samples, at an
      angle perpendicular to the direction of loading, suggests that these differences
      in Poisson's ratio may be due to improved organization of collagen network in the
      dynamically loaded samples.

PMID- 15990102
TI  - The effects of sloped surfaces on locomotion: a kinematic and kinetic analysis.
AB  - Previous findings from studies of demanding tasks in humans and slope walking in
      quadrupeds suggest that human slope walking may require specialized neural
      control strategies. The goal of this investigation was to gain insight into these
      strategies by quantifying lower limb kinematics and kinetics during up- and
      downslope walking. Nine healthy volunteers walked at a self-selected speed on an
      instrumented ramp at each of five grades (-39%, -15%, 0%, +15%, +39%; or -21
      degrees, -8.5 degrees, 0 degrees, +8.5 degrees, +21 degrees, respectively). For
      each subject, the selected speed was maintained at all grades to minimize the
      effect of speed on gait dynamics. Points of interest were identified in the
      kinematic and kinetic outcome measures and compared across grades; a significant
      grade effect was found for all points except the magnitude of the peak hip
      extensor moment during late stance. Kinematic postural changes were consistent
      with the need to raise the limb for toe clearance and heel strike and to lift the
      body during upslope walking, and to control the descent of the body during
      downslope walking. The support moment increased significantly during both upslope
      and downslope walking compared to level: the increases were predominantly due to
      the increasing hip extensor moment during upslope walking, and to the increasing
      knee extensor moment during downslope walking. In addition, the hip and knee
      joint moment patterns showed significant differences from the patterns observed
      during level walking. This non-uniform distribution of joint moment increases
      during up- and downslope walking compared to level walking suggests that these
      three tasks are not governed by the same control strategy.

PMID- 15990103
TI  - Characterization of the mechanical properties of skin by inverse analysis
      combined with the indentation test.
AB  - This study proposes a new method to determine the mechanical properties of human
      skin by the use of the indentation test [Pailler-Mattei, 2004. Caracterisation
      mecanique et tribologique de la peau humaine in vivo, Ph.D. Thesis, ECL-no. 2004
      31; Pailler-Mattei, Zahouani, 2004. Journal of Adhesion Science and Technology
      18, 1739-1758]. The principle of the measurements consists in applying an in vivo
      compressive stress [Zhang et al., 1994. Proceedings of the Institution of
      Mechanical Engineers 208, 217-222; Bosboom et al., 2001. Journal of Biomechanics
      34, 1365-1368; Oomens et al., 1984. Selected Proceedings of Meetings of European
      Society of Biomechanics, pp. 227-232; Oomens et al., 1987. Journal of
      Biomechanics 20(9), 877-885] on the skin tissue of an individual's forearm. These
      measurements show an increase in the normal contact force as a function of the
      indentation depth. The interpretation of such results usually requires a long and
      tedious phenomenological study. We propose a new method to determine the
      mechanical parameters which control the response of skin tissue. This method is
      threefold: experimental, numerical, and comparative. It consists combining
      experimental results with a numerical finite elements model in order to find out
      the required parameters. This process uses a scheme of extended Kalman filters
      (EKF) [Gu et al., 2003. Materials Science and Engineering A345, 223-233; Nakamura
      et al., 2000. Acta Mater 48, 4293-4306; Leustean and Rosu, 2003. Certifying
      Kalman filters. RIACS Technical Report 03.02, 27pp.
      http://gureni.cs.uiuc.edu/~grosu/download/luta + leo.pdf; Welch and Bishop, An
      introduction to Kalman filter, University of North Carolina at Chapel Hill, 16p.
      http://www.cs.unc.edu/~welch/kalman/]. The first results presented in this study
      correspond to a simplified numerical modeling of the global system. The skin is
      assumed to be a semi-infinite layer with an isotropic linear elastic mechanical
      behavior [Zhang et al., 1994. Proceedings of the Institution of Mechanical
      Engineers 208, 217-222] This analysis will be extended to more realistic models
      in further works.

PMID- 15990104
TI  - RSA wear measurements with or without markers in total hip arthroplasty.
AB  - Novel algorithms for radiostereometric (RSA) measurements of the femoral head and
      metal-backed, hemi-spherical cups of a total hip replacement are presented and
      evaluated on phantom images and clinical double examinations of 20 patients. The
      materials were analysed with classical RSA and three novel algorithms: (1) a dual
      projection head algorithm using the outline of the femoral head together with
      markers in the cup; (2) a marker-less algorithm based on measurements of the
      outline of the femoral head, the cup shell and opening circle of the cup; and (3)
      a combination of both methods. The novel algorithms improve current, marker
      based, RSA measurements, as well as allows studies without marked cups. This
      opens the possibility of performing wear measurements on larger group of
      patients, in clinical follow-ups, even retrospective studies. The novel
      algorithms may help to save patient data in current RSA studies lost due to
      insufficiently marked cups. Finally, the novel algorithms simplify the RSA
      procedure and allow new studies without markers, saving time, money, and reducing
      safety concerns. Other potential uses include migration measurements of re
      surfacing heads and measuring spherical sections as implant landmarks instead of
      markers.

PMID- 15990105
TI  - Dispersion of components in transport processes: velocity dispersion model.
AB  - This paper presents a new model of dispersion of components in transport
      processes. It is suggested that the flow velocity may be specified by a Gauss
      function with relative dispersion of flow velocity beta=sigmav/v; the overall
      dispersion of inert component (in porous as well as in homogeneous medium) may be
      calculated from the equation sigma=(2Dt/tau2 + (betavt)2)0.5, where D is the
      diffusion coefficient, t is time, tau is tortuosity, and v is flow velocity. The
      most common range of variability of relative dispersion of flow velocity in
      natural soils is 8-32%. The model is well applicable to column and field
      experiments.

PMID- 15990107
TI  - Transient electrophoresis of dielectric spheres.
AB  - The dynamic electrophoretic response of a spherical dielectric particle suspended
      in an electrolyte solution to a step change in the applied electrics field is
      analytically studied. The electrical double layer surrounding the particle may
      have either a small but finite thickness or a very large thickness relative to
      the particle radius. For the case of electrophoresis of a particle with a thin
      double layer, the local electroosmotic velocity at the outer edge of the double
      layer evolving with time after the external field is imposed is used as an
      apparent slip boundary condition at the particle surface so that the unsteady
      equation of motion for the fluid flow outside the double layer is solved. Closed
      form formulas for the transient electrophoretic mobility of the particle are
      derived as functions of relevant parameters. The results demonstrate that, when
      the double layer surrounding the particle is relatively thin, the normalized
      electrophoretic mobility at a given dimensionless time decreases monotonically
      with a decrease in the parameter kappaa, where kappa(-1) is the Debye screening
      length and a is the particle radius. When the double layer of the particle is
      relatively thick, the particle mobility can have magnitudes comparable to those
      for a particle with a thin double layer in the initial stage, but will become
      much smaller afterward. In general, the effect of the relaxation time for
      transient electrophoresis is negligible, regardless of the value of kappaa.

PMID- 15990106
TI  - A colloid "digesting" route to novel, thermally stable high surface area ZrO2 and
      Pd/ZrO2 catalytic materials.
AB  - Zirconia having high thermal stability and high surface area (up to 160 m(2)/g at
      700 degrees C) has been prepared by a colloidal "digesting" process. This
      material having demonstrated high surface areas at elevated temperatures was then
      applied as a catalyst support. A Pd colloid with diameter of approximately 12 nm
      has been successfully deposited on the high surface area zirconia material. All
      systems have been well characterized by TEM, X-ray diffraction, N2 adsorption
      isotherms, FTIR, elemental analysis and dynamic light scattering techniques. The
      colloidal Pd particles have been found homogeneously well dispersed in the
      hydrous zirconia matrix without aggregation. The Pd/ZrO2 catalysts have been
      screened for cyclohexene and 1-hexene hydrogenation activity and it was found
      that the catalyst is extremely active.

PMID- 15990108
TI  - Interactions between C.I. Basic Blue 41 and aluminosilicate sorbents.
AB  - Four aluminosilicate sorbents (montmorillonite, bentonite, raw perlite, and
      expanded perlite) were employed for retention of the cationic dye C.I. Basic Blue
      41. Interactions between the clay and the dyestuff were investigated at several
      temperatures and clay:dye ratios. The mechanism behind the adsorption involves
      the formation of H-aggregates of the dye on both clays, followed by dye migration
      into the interlayer in the case of montmorillonite. Time-dependent absorbance
      spectra revealed the presence of various dye species in montmorillonite.
      Introduction of the dye molecules into the interlamellar space occurs more
      rapidly in bentonite than in montmorillonite. The dye molecules inserted between
      the clay leaves adopt different orientations and, eventually, stack in layers at
      increased dye loadings for both montmorillonite and bentonite. Higher dye
      aggregates are then present as suggested by diffuse reflectance spectroscopy. Dye
      sorption on both raw and expanded perlite proceeds via H-aggregate formation as
      well.

PMID- 15990109
TI  - Direct quantitation of T cell signaling by laser scanning cytometry.
AB  - Current flow cytometric technology allows quantitative assessment of surface and
      intracellularly expressed molecules on isolated cells. However, the need to
      disrupt tissues prevents correlation of phenotypic expression with anatomical
      location. In contrast, immunohistochemistry in conjunction with conventional or
      confocal microscopy allows localisation of staining, but little in the way of
      quantitation. The laser scanning cytometer (LSC) allows a combination of both
      approaches, as it can apply quantitative flow cytometric laser technology to
      intact tissue. The purpose of this protocol is to describe in vitro and ex vivo
      methods for quantifying cell signaling molecule expression and activation within
      antigen-specific T cells by laser scanning cytometry.

PMID- 15990110
TI  - DeltaPKC-mediated activation of epsilonPKC in ethanol-induced cardiac protection
      from ischemia.
AB  - Previous studies have demonstrated that acute ethanol exposure induces activation
      of delta protein kinase C (deltaPKC) and epsilonPKC, and mimics ischemic
      preconditioning via epsilonPKC activation. However, the role of deltaPKC isozyme
      in ischemia and reperfusion is still controversial. Here, we investigated the
      role of deltaPKC in ethanol-induced cardioprotection using a selective deltaPKC
      activator (psideltaRACK), or inhibitor (deltaV1-1), and a selective epsilonPKC
      inhibitor (epsilonV1-2) in isolated mouse hearts. Mice were injected
      intraperitoneally or by gavage with ethanol, regulators of delta and epsilonPKC
      or an adenosine A1 receptor blocker (DPCPX). Isolated perfused mouse hearts were
      subjected to a 30-min global ischemia and a 120-min reperfusion, ex vivo.
      Injection of 0.5 g/kg ethanol 1 h, but not 10 min, before ischemia reduced
      infarct size and CPK release. Pretreatment with epsilonV1-2 abolished this
      ethanol-induced cardioprotection. Pretreatment with deltaV1-1 induced
      cardioprotection when injected with ethanol (0.5 g/kg) 10 min before ischemia,
      but deltaV1-1 partly inhibited ethanol-induced cardioprotection when injected
      with ethanol 1-h before the onset of ischemia. psideltaRACK injection 1 h, but
      not 10 min, before ischemia induced cardioprotection and translocation of
      epsilonPKC from the cytosol to the particulate fraction. Pretreatment with DPCPX
      or epsilonV1-2 inhibited psideltaRACK-induced cardioprotection and translocation
      of epsilonPKC. Therefore, activation of deltaPKC-induced by ethanol or by the
      deltaPKC activator is cardioprotective, provided that sufficient time passes to
      allow deltaPKC-induced activation of epsilonPKC, an A1 adenosine receptor
      dependent process.

PMID- 15990111
TI  - The crystal structure of free human hypoxanthine-guanine
      phosphoribosyltransferase reveals extensive conformational plasticity throughout
      the catalytic cycle.
AB  - Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the
      synthesis of the purine nucleoside monophosphates, IMP and GMP, by the addition
      of a 6-oxopurine base, either hypoxanthine or guanine, to the 1-beta-position of
      5-phospho-alpha-d-ribosyl-1-pyrophosphate (PRib-PP). The mechanism is sequential,
      with PRib-PP binding to the free enzyme prior to the base. After the covalent
      reaction, pyrophosphate is released followed by the nucleoside monophosphate. A
      number of snapshots of the structure of this enzyme along the reaction pathway
      have been captured. These include the structure in the presence of the inactive
      purine base analogue, 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and PRib
      PP.Mg2+, and in complex with IMP or GMP. The third structure is that of the
      immucillinHP.Mg(2+).PP(i) complex, a transition-state analogue. Here, the first
      crystal structure of free human HGPRT is reported to 1.9A resolution, showing
      that significant conformational changes have to occur for the substrate(s) to
      bind and for catalysis to proceed. Included in these changes are relative
      movement of subunits within the tetramer, rotation and extension of an active
      site alpha-helix (D137-D153), reorientation of key active-site residues K68, D137
      and K165, and the rearrangement of three active-site loops (100-128, 165-173 and
      186-196). Toxoplasma gondii HGXPRT is the only other 6-oxopurine
      phosphoribosyltransferase structure solved in the absence of ligands. Comparison
      of this structure with human HGPRT reveals significant differences in the two
      active sites, including the structure of the flexible loop containing K68 (human)
      or K79 (T.gondii).

PMID- 15990112
TI  - Structural basis of the interaction between P-element somatic inhibitor and U1
      70k essential for the alternative splicing of P-element transposase.
AB  - P-element transposition in Drosophila is regulated by tissue-specific alternative
      splicing of the P-element transposase pre-mRNA. In somatic cells, the P-element
      somatic inhibitor (PSI) protein binds to exon 3 of the pre-mRNA and recruits U1
      small nuclear ribonucleoprotein (snRNP) to the F1 pseudo-splice site. This
      abrogates binding of U1 snRNP to the genuine 5' splice site, thereby preventing
      excision of the third intron. Two homologous short sequences, referred to as the
      A and B boxes, near the C terminus of PSI bind to U1-70k protein within U1 snRNP.
      We have now mapped the AB box-binding site of U1-70k to a short proline-rich
      sequence at the C terminus. Our NMR study shows that the B box forms an anti
      parallel helical hairpin in which four highly conserved aromatic residues form a
      cluster on one face of the first helix. This hydrophobic cluster interacts
      extensively with the proline-rich region of the U1-70k protein.

PMID- 15990113
TI  - Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a
      mouse model of Amyotrophic Lateral Sclerosis.
AB  - Insulin-like growth factor (IGF)-1 has been shown to have a protective effect on
      motor neurons both in vitro and in vivo, but has limited efficacy in patients
      with amyotrophic lateral sclerosis (ALS) when given subcutaneously. To examine
      the possible effectiveness of IGF-1 in a mouse model of familial ALS, transgenic
      mice expressing human Cu/Zn superoxide dismutase (SOD1) with a G93A mutation were
      treated by continuous IGF-1 delivery into the intrathecal space of the lumbar
      spinal cord. We found that the intrathecal administration of IGF-1 improved motor
      performance, delayed the onset of clinical disease, and extended survival in the
      G93A transgenic mice. Furthermore, it increased the expression of phosphorylated
      Akt and ERK in spinal motor neurons, and partially prevented motor neuron loss in
      these mice. Taken together, the results suggest that direct administration of IGF
      1 into the intrathecal space may have a therapeutic benefit for ALS.

PMID- 15990114
TI  - Extrathymic malignancies in patients with myasthenia gravis.
AB  - INTRODUCTION: Myasthenia gravis (MG) is considered a paraneoplastic phenomenon of
      thymomas in 15% of patients. Co-existence of MG with extrathymic malignancies,
      and an increased risk of second malignancy in patients with thymoma have been
      reported. Data on clinical characteristics of MG patients with extrathymic
      malignancies and the role of concomitant diseases and their treatment are
      lacking. METHODS: The clinical records of 188 consecutive MG patients were
      studied retrospectively. We examined whether gender, age, generalized disease,
      seropositivity for acetyl-choline receptor antibodies, occurrence of thymoma,
      immunosuppressive therapy and occurrence of other autoimmune diseases determined
      an increased risk for development of extrathymic malignancy. RESULTS: This group
      followed the typical epidemiological characteristics of MG. Thirty-three patients
      (17.6%) had a thymoma. Twenty-nine patients (15.4%) had 30 extrathymic malignant
      tumors of various origins. Only four patients with extrathymic tumors had an
      associated thymoma. Tumors were diagnosed between 20 years prior to and 35 years
      after the appearance of MG. Older age of MG onset was the only risk factor
      identified for development of malignancy in MG. DISCUSSION: Extrathymic
      malignancies are common in MG patients, especially in the older age group. There
      are no specific clinical features of the subgroup of MG patients with cancer.
      Although MG is not a paraneoplastic phenomenon of extrathymic malignancy, the
      association between MG and malignancy may be due to a common background of immune
      dysregulation.

PMID- 15990115
TI  - AD with subcortical white matter lesions and vascular dementia: CSF markers for
      differential diagnosis.
AB  - We investigated whether the cerebrospinal fluid (CSF) biomarkers beta-amyloid 1
      42 (Abeta1-42), total tau (t-tau) protein and tau protein phosphorylated at
      threonine 181 (p-tau181) could discriminate Alzheimer's disease (AD) from
      vascular dementia (VD) patients. CSF samples of Abeta1-42, t-tau, and p-tau181
      were collected from probable AD (n=35), probable AD with white matter changes
      (WMC) indicative of concomitant cerebrovascular disorder (CVD, n=31), VD (n=20),
      and an age-matched subgroup of patients with other neurological disorders (OND)
      without cognitive impairment (n=24). AD patients showed very low Abeta1-42 levels
      (median=393 pg/ml). Abeta1-42, but not t-tau, differentiated AD from VD patients.
      However, the markers did not discriminate AD vs. AD plus WMC. In particular, both
      subgroups showed similar CSF biomarkers but they were significantly different
      from VD. ROC analysis showed that Abeta1-42 could discriminate AD from VD
      (AUC=0.85). The cutoff of 493 pg/ml gave sensitivity and specificity values of
      77% and 80%, respectively. Similar results were obtained when Abeta1-42 was
      employed to discriminate AD with WMC from VD (95% specificity and 60%
      sensitivity, but with cutoff of 750 pg/ml). T-tau increased aspecifically in all
      cognitively impaired patients. P-tau181 performed better than t-tau in
      discriminating AD (with or without WMC) vs. VD. In conclusion, Abeta1-42 proved
      to be a valuable tool to discriminate AD vs. VD patients and possibly to improve
      diagnostic accuracy in clinical forms, improperly classified as "mixed dementia"
      based on radiological vascular lesions.

PMID- 15990116
TI  - Expanding use of botulinum toxin.
AB  - Botulinum toxin type A (BTX-A) is best known to neurologists as a treatment for
      neuromuscular conditions such as dystonias and spasticity and has recently been
      publicized for the management of facial wrinkles. The property that makes
      botulinum toxin type A useful for these various conditions is the inhibition of
      acetylcholine release at the neuromuscular junction. Although botulinum toxin
      types A and B (BTX-A and BTX-B) continue to find new uses in neuromuscular
      conditions involving the somatic nervous system, it has also been recognized that
      the effects of these medications are not confined to cholinergic neurons at the
      neuromuscular junction. Acceptors for BTX-A and BTX-B are also found on autonomic
      nerve terminals, where they inhibit acetylcholine release at glands and smooth
      muscle. This observation led to trials of botulinum neurotoxins in various
      conditions involving autonomic innervation. The article reviews the emerging use
      of botulinum neurotoxins in these and selected other conditions, including
      sialorrhea, primary focal hyperhidrosis, pathological pain and primary headache
      disorders that may be of interest to neurologists and related specialists.

PMID- 15990117
TI  - Density-dependence as a size-independent regulatory mechanism.
AB  - The growth function of populations is central in biomathematics. The main dogma
      is the existence of density-dependence mechanisms, which can be modelled with
      distinct functional forms that depend on the size of the population. One
      important class of regulatory functions is the theta-logistic, which generalizes
      the logistic equation. Using this model as a motivation, this paper introduces a
      simple dynamical reformulation that generalizes many growth functions. The
      reformulation consists of two equations, one for population size, and one for the
      growth rate. Furthermore, the model shows that although population is density
      dependent, the dynamics of the growth rate does not depend either on population
      size, nor on the carrying capacity. Actually, the growth equation is uncoupled
      from the population size equation, and the model has only two parameters, a
      Malthusian parameter rho and a competition coefficient theta. Distinct sign
      combinations of these parameters reproduce not only the family of theta
      logistics, but also the van Bertalanffy, Gompertz and Potential Growth equations,
      among other possibilities. It is also shown that, except for two critical points,
      there is a general size-scaling relation that includes those appearing in the
      most important allometric theories, including the recently proposed Metabolic
      Theory of Ecology. With this model, several issues of general interest are
      discussed such as the growth of animal population, extinctions, cell growth and
      allometry, and the effect of environment over a population.

PMID- 15990118
TI  - Model for energy oscillations in cells.
AB  - Rapid periodic pulses have been observed in yeast cell walls and these pulsations
      must be accompanied by coherent oscillations of energy. Such energy oscillations
      are likely to be a common feature in cells and we explore other consequences,
      either known or unknown, that may originate from chemical oscillations of small
      amplitude. We do not consider specific mechanisms for the energy oscillations,
      but here we accept their existence as a fact following from the yeast
      experiments. Chemical oscillators are treated as generic quantum oscillators and
      this model predicts that observed frequencies should have a simple volume
      dependence where smaller cells exhibit higher frequencies than their larger
      counterparts. An extension to multicellular organisms then affords a derivation
      of the celebrated Kleiber law that evaluates both the numerical coefficient and
      the 34 exponent of mass. Calculations of activation energies and efficiencies at
      experimental temperatures follow. Finally, the model is applied to derive
      established expressions for blood flow and pulse rate. We conclude that the model
      reflects some common metabolic process insofar as it agrees with diverse
      quantitative findings while using minimal input data and without introducing free
      parameters.

PMID- 15990119
TI  - The distribution of fitness effects among beneficial mutations in Fisher's
      geometric model of adaptation.
AB  - Recent models of adaptation at the DNA sequence level assume that the fitness
      effects of new mutations show certain statistical properties. In particular,
      these models assume that the distribution of fitness effects among new mutations
      is in the domain of attraction of the so-called Gumbel-type extreme value
      distribution. This assumption has not, however, been justified on any biological
      or theoretical grounds. In this note, I study random mutation in one of the
      simplest models of mutation and adaptation-Fisher's geometric model. I show that
      random mutation in this model yields a distribution of mutational effects that
      belongs to the Gumbel type. I also show that the distribution of fitness effects
      among rare beneficial mutations in Fisher's model is asymptotically exponential.
      I confirm these analytic findings with exact computer simulations. These results
      provide some support for the use of Gumbel-type extreme value theory in studies
      of adaptation and point to a surprising connection between recent phenotypic- and
      sequence-based models of adaptation: in both, the distribution of fitness effects
      among rare beneficial mutations is approximately exponential.

PMID- 15990120
TI  - Pharmacological characterisation of voltage-dependent Ca2+ channels in isolated
      ganglia from the myenteric plexus.
AB  - Voltage-dependent Ca2+ channels of fura-2-loaded ganglionic cells from the
      myenteric plexus of newborn rats were pharmacologically characterised. In
      contrast to completely dissociated myenteric cells, intact ganglia showed a
      stronger loading with the Ca2+-sensitive dye and a reproducible stimulation of
      the fura-2 signal by the cholinergic agonist, carbachol. A depolarisation-induced
      increase in the intracellular Ca2+ concentration ([Ca2+]i) was induced by
      superfusion with 35 mmol l(-1) KCl. This increase in [Ca2+]i was sensitive to
      Ni2+ and Co2+ as well as omega-conotoxin MVIIA, omega-agatoxin IVA, and SNX-482.
      The strongest inhibition was achieved by nifedipine (5 x 10(-7) mol l(-1)) and
      omega-conotoxin GVIA (4.3 x 10(-7) mol l(-1)). These two blockers also inhibited
      the [Ca2+]i increase evoked by nicotinic receptor stimulation. Consequently,
      isolated myenteric ganglia in culture express different types of voltage
      dependent Ca2+ channels, from which the L- and the N-type seem to be the most
      important. When exposed to mediators of inflammation such as tumor necrosis
      factor-alpha (TNF-alpha) or different prostaglandins, no pronounced alterations
      in the fura-2 ratio were observed suggesting that changes in the Ca2+-signalling
      are not centrally involved in the response of enteric ganglionic cells to these
      paracrine substances.

PMID- 15990121
TI  - Multielemental accumulation and its intracellular distribution in tissues of some
      aquatic birds.
AB  - This study was aimed at determining multielemental concentration and its
      intracellular distribution in selected tissues of cormorant and waterfowl
      species. Non-essential elements such as Hg, Tl, Cd, Pb and V in tissues were
      generally consistent with those in ingested items, indicating the significance of
      food sources of non-essential metal accumulation in great cormorants and
      mallards. Great cormorants and four waterfowl species examined reflected natural
      background levels of toxic metals such as Cd, Hg and Pb as well as some essential
      elements, indicating no specific metal exposure from local sources. Most of Cu,
      Zn, Se, Rb, Ag, Cd, Cs, and Hg contents were present in the hepatocytosolic
      fraction, whereas a large percentage of V and Mo were present in insoluble
      fraction in great cormorant, mallard, and spot-billed duck. The major role of
      these subcelluar fractions in elemental regulation accounts for the high
      percentage contribution of each cellular fraction to the total metal contents.
      Cadmium and Cu are chiefly sequestered through binding to metallothioneins (MTs)
      of hepatocytosolic fraction in these three avian species. Both MTs and high
      molecular-weight substance (HMWS) for Zn and low-molecular-weight substance
      (LMWS) for Rb were also involved in their sequestration in cytosolic fractions.
      Relatively different species-specific cytosolic substances were responsible for
      varying degrees of Ag, Mn, and Co accumulation. It is worth noting that these
      intracellular metal levels in birds are closely regulated by metal-associated
      cellular constituents. Therefore, risk assessment studies of metal accumulation
      in such wild birds should take intracellular metal distribution and specific
      cellular constituents into account.

PMID- 15990122
TI  - The utility of genetically altered mouse models for nutrition and cancer
      chemoprevention research.
AB  - The development of effective cancer preventive interventions is being enhanced by
      the use of relevant animal models to confirm, refine, and extend potential leads
      from clinical and epidemiologic studies. In particular, genetically altered mice,
      with specific cancer-related genes modulated, are providing powerful tools for
      studying carcinogenesis, as well as important conduits for translating basic
      research findings from the laboratory bench to the bedside. This review explores
      the utility of genetically altered mice for developing cancer preventive
      strategies that can offset increased cancer susceptibility resulting from
      specific genetic lesions. Examples will focus on preventing cancer by dietary
      interventions, particularly obesity prevention/energy balance modulation, as well
      as chemoprevention, in mice with alterations in genes such as the p53 or Apc
      tumor suppressors, components of the ErbB pathway, and other pathways frequently
      altered in human cancer.

PMID- 15990123
TI  - Enhanced stimulation of chromosomal translocations and sister chromatid exchanges
      by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces
      cerevisiae yku70 mutants.
AB  - DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or
      non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both
      MATa and MATalpha inhibits NHEJ and facilitates DSB-initiated HR. We previously
      observed that DSB-initiated recombination between two his3 fragments, his3
      Delta5' and his3-Delta3'::HOcs is enhanced in haploids and diploids expressing
      both MATa and MATalpha genes, regardless of the position or orientation of the
      his3 fragments. Herein, we measured frequencies of DNA damage-associated
      translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants,
      defective in NHEJ. Translocation and SCE frequencies were measured in strains
      containing the same his3 fragments after DSBs were made directly at trp1::his3
      Delta3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation
      and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4
      nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated
      translocations were five-fold higher in yku70 mutants compared to wild type;
      however, frequencies of phleomycin-associated translocations were lower in the
      yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in
      the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated
      sequences on non-homologous chromosomes and sister chromatids occurs at higher
      frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage
      associated HR in yku70 mutants depend on the DNA damaging agent.

PMID- 15990124
TI  - Relationships between familial risks of cancer and the effects of heritable genes
      and their SNP variants.
AB  - Familial risks for cancer can be used in many ways in guiding gene identification
      efforts and, more broadly, in understanding cancer etiology. Gene identification
      efforts may be properly designed and targeted if the familial risks are well
      characterized and the mode of inheritance is identified. Single nucleotide
      polymorphisms (SNPs) are extensively used in case-control studies of practically
      all cancer types. They are used for the identification of inherited cancer
      susceptibility genes and those that may interact with environmental factors.
      However, being genetic markers, they are applicable only on heritable conditions,
      which is often a neglected fact. Based on the data in the nationwide Swedish
      Family-Cancer Database, we review familial risks for all main cancers and discuss
      the evidence for a heritable component in cancer. The available evidence,
      including differences in cancer incidence between regions and temporal changes
      within regions, indicates that cancer is mainly an environmental disease, with a
      minor heritable etiology. The large environmental component will hamper the
      success of SNP-based genetic association studies. Empirical familial risks should
      be used to evaluate the feasibility of such studies. We develop figures for the
      assessment of genetic parameters based on familial risks. Such data are helpful
      in the estimation of the expected genetic effects in cancer. Overall, we consider
      the likelihood of a successful application of SNPs in gene-environment studies
      small, unless established environmental risk factors are tested on proven
      candidate genes.

PMID- 15990125
TI  - The influence of N-dialkyl and other cationic substituents on DNA intercalation
      and genotoxicity.
AB  - DNA intercalation by small chemical molecules can result in frameshift
      mutagenesis and chromosomal breakage. With evidence mounting that broadly diverse
      structures are capable of intercalating between DNA base pairs, it becomes
      important to better define those structural features that enhance intercalation
      strength and those that confer genotoxicity particularly among those
      intercalators that do not have the classical planar tricyclic fused ring
      structure. A chemical substituent that is present on many pharmaceutical and
      other biologically active molecules is the N-dialkyl group. In the present study,
      we investigate if and how the presence of an aromatic N-dialkyl or other cationic
      group affects the genotoxicity and DNA intercalation ability of 26 selected
      acridines, phenothiazines, benzophenones, triphenylethylenes and other classes of
      molecules. The data were obtained from the literature, from experiments using a
      cell-based DNA intercalation assay, and from modeling studies using a three
      dimensional computational DNA docking program. It is demonstrated that cationic
      substitution can enhance both genotoxicity and electrostatic interactions within
      a chemical/DNA intercalation complex.

PMID- 15990126
TI  - Flavor preference conditioning as a function of fat source.
AB  - Rats learn to prefer foods based, in part, on postingestive nutrient actions.
      This study compared the effectiveness of intragastric (IG) infusions of fat
      emulsions which varied in their fatty acid composition (chain length and
      saturation) to condition preferences for flavored saccharin solutions. In
      Experiment 1, food-restricted rats were trained (30 min/day) with one flavor
      (CS+CO) paired with IG corn oil (CO) and a second flavor (CS+MCT) paired with IG
      medium chain triglyceride (MCT); the fats were prepared as isocaloric emulsions.
      A third flavor (CS-) was paired with IG water. The rats subsequently showed a
      strong preference for the CS+CO (84%) and a weaker preference for the CS+MCT
      (65%) relative to the CS-. In a direct choice test, the CS+CO was preferred to
      the CS+MCT by 75%. In Experiment 2, new rats trained with flavors paired with IG
      corn oil and beef tallow (BT) infusions learned to prefer both the CS+CO (89%)
      and the CS+BT (82%) relative to the CS-, and preferred the CS+CO to the CS+BT by
      67%. The same rats were trained with three new flavors paired with IG infusions
      of corn oil, vegetable shortening (VS), and water. The rats strongly preferred
      both the CS+CO (91%) and CS+VS (86%) over the CS-, and they preferred the CS+CO
      to the CS+VS by 64%. In Experiment 3, new rats trained with corn oil and
      safflower oil (SO) paired flavors preferred both the CS+CO and CS+SO to the CS-,
      and equally preferred the CS+CO and CS+SO in two-bottle tests. The rats were also
      given one-and two-bottle tests with the various fat emulsions and their
      preference profile was consistent with their conditioned preferences for the
      flavored saccharin solutions. These findings demonstrate that many different fat
      sources can condition flavor preferences. Fats with high polyunsaturated content
      and/or lower saturated fat content are the most reinforcing.

PMID- 15990127
TI  - Positive benefits of a pharmacist-managed hypertension clinic in Nigeria.
AB  - OBJECTIVE: The aim of this study was to determine whether the provision of
      further practice-based support by pharmacists will bring about improved outcomes
      for blood pressure (BP) control in middle-aged and elderly Nigerian hypertensive
      patients managed with combination diuretics (amiloride hydrochloride 5
      mg+hydrochlorothiazide 50 mg) and/or methyl dopa at the primary care level.
      DESIGN AND SETTING: This was a 1-year prospective, randomized cohort study of the
      outpatients of a state comprehensive health centre in South-western Nigeria. Free
      primary health services including free drugs were provided for all patients.
      PATIENTS AND METHOD: The study population comprised 51 Nigerian patients with
      uncomplicated hypertension aged 45 years or more, with a 0.2-3.0-year history of
      hypertension, registered at the Comprehensive Health Centre, Ife between October
      2002 and March 2003. They were invited into the pharmacist-managed hypertension
      clinic and followed for the study period. Participating pharmacists counselled
      for current medication, personalized goals of lifestyle modification stressing
      weight loss and/or increased activity, increased patient awareness by providing
      relevant education about hypertension and associated/related diseases, adjusted
      drug therapy to optimize effectiveness and minimize adverse events, utilized
      treatment schedules that enhanced patients' adherence to therapy, and monitored
      treatment outcomes between enrollment and return visits. Patient satisfaction and
      the number of treatment failures within 6 months post enrollment were compared
      with retrospective data from our earlier study involving physician-managed
      patients under a similar setting. RESULTS: Uncontrolled BP reduced from 92 to
      36.2% by 10.15+/-5.02 days after enrollment. Treatment failures were observed at
      5.9% of the total return visits (n=184) within 6 months. CONCLUSION: Pharmacist
      managed hypertension clinics can improve BP control, reduce treatment failure and
      increase patient satisfaction.

PMID- 15990128
TI  - Reliability of cause-specific mortality rate statistics: case of Lithuania.
AB  - OBJECTIVES: To evaluate the reliability of cause-specific mortality rate
      statistics. STUDY DESIGN: The underlying causes of death among different
      demographic groups in a territorial unit of Lithuania were verified and the data
      were compared with the corresponding official statistics. METHODS: Community
      based autopsy and expert analysis of medical records. RESULTS: The study
      contingent consisted of 1474 permanent residents aged 0-101 years [809 (54.9%)
      males and 665 (45.1%) females] who had died in hospital (n=546, 37%) and out of
      hospital (n=928, 63%) in 1989-1991. The underlying cause of death was verified in
      98.6% of cases by full autopsy (69.9%) and expert analysis of medical records
      (28.7%). Circulatory system diseases were found to be implicated in 44.4% of all
      deaths (35.9% of males and 54.7% of females), malignant neoplasms were the cause
      of 19.4% of deaths (21.5 and 16.8%, respectively) and external causes were
      responsible for 19.4% of deaths (27.3 and 9.8%, respectively). Cause-specific
      mortality rates were sex and age dependent. CONCLUSIONS: The proportion of
      circulatory system diseases in the cause-specific mortality structure was found
      to be significantly lower, and that of external causes (injury and poisoning) was
      found to be higher than the corresponding proportions presented by official
      Lithuanian statistics. Verified cardiovascular death rates corresponded with
      those in the European Union as a whole.

PMID- 15990129
TI  - Human cystic echinococcosis in two Mongolian communities in Hobukesar (China) and
      Bulgan (Mongolia).
AB  - In order to investigate the prevalence of human cystic echinococcosis (CE) in
      traditional Mongolian communities in western Mongolia and Xinjiang (northwest
      China), studies were carried out between 1995 and 2000, on two ethnically
      identical populations in Hobukesar (China) and Bulgan (Mongolia). The prevalence
      of human hepatic CE in the two communities was significantly different. In
      Hobukesar, human CE prevalence by ultrasound was 2.7% (49/1844), while in Bulgan
      it was 0.2% (4/1609) (P<0.001). Dog surveys showed that coproantigen-positive
      rates or dog necropsy positives were similar in both communities (35.0% in
      Hobukesar and 35.7% in Bulgan). Comparing possible risk factors, there appeared
      to be some significant differences between the two communities, which might
      contribute to the observed difference in CE prevalence. These included: the
      proportion of herdsman or farmers recorded; the proportions of dog ownership and
      livestock ownership; and the proportion of families practising home slaughter.
      The presence of a Russian dog-dosing programme up to the mid-1980s may explain
      the lower prevalence of human CE in the Bulgan population; no similar programme
      operated in the China-administered Hobukesar community.

PMID- 15990130
TI  - How can toxicogenomics inform risk assessment?
AB  - Technologies that generate information about the genome are being used to explore
      changes in gene expression and related proteins following exposure to chemicals.
      Conceptually, this information allows a greater understanding of genomic level
      mRNA expression (transcriptomics), cell and tissue protein expression
      (proteomics) and information about metabolite profiles (metabonomics). Having a
      greater understanding of this information alongside, empirical toxicological
      reference data provide for the continued evolution in our ability to understand
      toxicological modes of action, thereby providing a more scientific basis for
      extrapolation of toxicological information from animals to humans. Toxicogenomics
      also provides specific opportunities for improvements at different stages of the
      risk assessment process such as the development of new predictive models for
      identifying human health hazards and the identification of more precise molecular
      biomarkers of exposure. One possibility is that molecular fingerprinting in vivo
      or in vitro can be used to categorize chemicals and mixtures of chemicals into
      different mode of action groups. As there is indication that molecular signals
      differ at dose levels, it is hoped that toxicogenomic information can also
      contribute to the understanding and interpretation of effects seen with low dose
      exposure. Several gene polymorphisms have already been identified which play a
      role in the differing intra-species response to chemicals thus providing
      explanation for the observed differences in effects. It is therefore likely that
      a better understanding of genomic expression will enable a greater insight into
      the factors behind the observed variability in susceptibility to chemical
      exposure that can be seen in human populations.

PMID- 15990131
TI  - Scientific basis for the Precautionary Principle.
AB  - The Precautionary Principle is based on two general criteria: (a) appropriate
      public action should be taken in response to limited, but plausible and credible,
      evidence of likely and substantial harm; (b) the burden of proof is shifted from
      demonstrating the presence of risk to demonstrating the absence of risk. Not much
      has been written about the scientific basis of the precautionary principle, apart
      from the uncertainty that characterizes epidemiologic research on chronic
      disease, and the use of surrogate evidence when human evidence cannot be
      provided. It is proposed in this paper that a new scientific paradigm, based on
      the theory of evolution, is emerging; this might offer stronger support to the
      need for precaution in the regulation of environmental risks. Environmental
      hazards do not consist only in direct attacks to the integrity of DNA or other
      macromolecules. They can consist in changes that take place already in utero, and
      that condition disease risks many years later. Also, environmental exposures can
      act as "stressors", inducing hypermutability (the mutator phenotype) as an
      adaptive response. Finally, environmental changes should be evaluated against a
      background of a not-so-easily modifiable genetic make-up, inherited from a period
      in which humans were mainly hunters-gatherers and had dietary habits very
      different from the current ones.

PMID- 15990132
TI  - Assessment of hepatotoxic liabilities by transcript profiling.
AB  - Male Wistar rats were treated with various model compounds or the appropriate
      vehicle controls in order to create a reference database for toxicogenomics
      assessment of novel compounds. Hepatotoxic compounds in the database were either
      known hepatotoxicants or showed hepatotoxicity during preclinical testing.
      Histopathology and clinical chemistry data were used to anchor the transcript
      profiles to an established endpoint (steatosis, cholestasis, direct acting,
      peroxisomal proliferation or nontoxic/control). These reference data were
      analyzed using a supervised learning method (support vector machines, SVM) to
      generate classification rules. This predictive model was subsequently used to
      assess compounds with regard to a potential hepatotoxic liability. A steatotic
      and a non-hepatotoxic 5HT(6) receptor antagonist compound from the same series
      were successfully discriminated by this toxicogenomics model. Additionally, an
      example is shown where a hepatotoxic liability was correctly recognized in the
      absence of pathological findings. In vitro experiments and a dog study confirmed
      the correctness of the toxicogenomics alert. Another interesting observation was
      that transcript profiles indicate toxicologically relevant changes at an earlier
      timepoint than routinely used methods. Together, these results support the useful
      application of toxicogenomics in raising alerts for adverse effects and
      generating mechanistic hypotheses that can be followed up by confirmatory
      experiments.

PMID- 15990133
TI  - Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat
      hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene.
AB  - We previously reported the finding that prenatal exposure to a relatively low
      dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a
      high dose decreased it. One of the most important factors determining the
      sensitivity to mammary carcinogenesis is the metabolic stage at administration of
      the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism
      to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct
      this metabolism. We investigated the hepatic expression of CYP1 and AhR following
      oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague
      Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 microg of
      PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative
      RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of
      PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and
      AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 microg group)
      prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and
      immunohistochemical analyses were consistent with mRNAs changes. Because DMBA
      oxidation produces a highly mutagenic metabolite and is finally catalyzed by
      CYP1B1, a relatively low PCB126 dose might produce the biological character to
      potentially increase the risk of DMBA-induced mammary carcinoma.

PMID- 15990134
TI  - DNA adducts: mass spectrometry methods and future prospects.
AB  - Detection of DNA adducts is widely used for the monitoring of exposure to
      genotoxic carcinogens. Knowledge of the nature and amounts of DNA adducts formed
      in vivo also gives valuable information regarding the mutational effects that may
      result from particular exposures. The power of mass spectrometry (MS) to achieve
      qualitative and quantitative analyses of human DNA adducts has increased greatly
      in recent years with the development of improved chromatographic interfaces and
      ionisation sources. Adducts have been detected on nucleic acid bases, 2'
      deoxynucleosides or 2'-deoxynucleotides, with LC-MS/MS being the favoured
      technique for many of these analyses. Our current applications of this technique
      include the determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine, which was
      postulated to be found as a DNA repair product in urine following exposure to
      acrylamide, and of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'
      deoxyadenosine, as markers of oxidative damage in human lymphocyte DNA. Higher
      sensitivity (with a detection limit of 1-10 adducts/10(12) nucleotides) may be
      achieved by the use of accelerator mass spectrometry (AMS), although this
      requires the presence of certain isotopes, such as [(14)C], in the material being
      analysed. In order to make this technique more amenable for studies of human
      exposure to environmental carcinogens, new postlabelling techniques,
      incorporating [(14)C] into specific DNA adducts after formation, are being
      developed. It is expected that combining the use of advanced MS techniques with
      existing (32)P-postlabelling and immunochemical methodologies will contribute
      greatly to the understanding of the burden of human exposure to environmental
      carcinogens.

PMID- 15990135
TI  - Placenta--an alternative source of stem cells.
AB  - The two most promising practical applications of human stem cells are cellular
      replacement therapies in human disease and toxicological screening of candidate
      drug molecules. Both require a source of human stem cells that can be isolated,
      purified, expanded in number and differentiated into the cell type of choice in a
      controlled manner. Currently, uses of both embryonic and adult stem cells are
      investigated. While embryonic stem cells are pluripotent and can differentiate
      into any specialised cell type, their use requires establishment of embryonic
      stem cell lines using the inner cell mass of an early pre-implantation embryo. As
      the blastocyst is destroyed during the process, ethical issues need to be
      carefully considered. The use of embryonic stem cells is also limited by the
      difficulties in growing large numbers of the cells without inducing spontaneous
      differentiation, and the problems in controlling directed differentiation of the
      cells. The use of adult stem cells, typically derived from bone marrow, but also
      from other tissues, is ethically non-controversial but their differentiation
      potential is more limited than that of the embryonic stem cells. Since human cord
      blood, umbilical cord, placenta and amnion are normally discarded at birth, they
      provide an easily accessible alternative source of stem cells. We review the
      potential and current status of the use of adult stem cells derived from the
      placenta or umbilical cord in therapeutic and toxicological applications.

PMID- 15990136
TI  - New models and molecular markers in evaluation of developmental toxicity.
AB  - Mammalian and non-mammalian embryos and embryonic stem cells may be used as
      models in mechanistic studies and in testing embryotoxicity of compounds. In
      addition to conventional culture methods, genetic modifications and use of
      molecular markers offer significant advantages in mechanistic studies as well as
      in developing new test methods for embryotoxicity. Zebrafish model has been used
      for a long time and at present several applications are available. It is an easy
      vertebral non-mammalian model, whose genome is largely known and several genetic
      modifications are easily constructed to study gene expression or knocked down
      genes. Fluorescent marker proteins can be used also in zebrafish to indicate gene
      activation in transgenic models. Chemical genetics approach has been developed
      using zebrafish model. This is a new approach to screen small molecules that
      regulate signaling pathways. Embryonic stem cells have been used in mechanistic
      studies and mouse embryonic stem cell test has been validated to study
      embryotoxicity in vitro. This method has been improved using quantitative
      measurements of molecular endpoints by real-time RT-PCR or fluorescent activated
      cell sorting methods (FACS). Methods facilitating differentiation to several
      different cell types are available. We have studied preimplantation mouse embryos
      as a possible model for in vitro testing. In this method, superovulated and in
      vivo fertilized preimplantation embryos were collected at morula stage and
      cultured up to blastocysts. The mouse preimplantation culture test was improved
      by quantitative gene expression measurement using two-step real-time RT-PCR
      methods. New endpoints improve the tests of in vitro embryotoxicity because
      subjective assessments are replaced by objective measurements. In addition,
      automation is possible and less time is needed for analysis. Thus, high
      throughput screening will come possible to test large numbers of compounds.

PMID- 15990137
TI  - Particulate matter and heart disease: evidence from epidemiological studies.
AB  - The association between particulate matter and heart disease was noted in the mid
      nineties of last century when the epidemiological evidence for an association
      between air pollution and hospital admissions due to cardiovascular disease
      accumulated and first hypotheses regarding the pathomechanism were formulated.
      Nowadays, epidemiological studies have demonstrated coherent associations between
      daily changes in concentrations of ambient particles and cardiovascular disease
      mortality, hospital admission, disease exacerbation in patients with
      cardiovascular disease and early physiological responses in healthy individuals
      consistent with a risk factor profile deterioration. In addition, evidence was
      found that annual average PM(2.5) exposures are associated with increased risks
      for mortality caused by ischemic heart disease and dysrhythmia. Thereby, evidence
      is suggesting not only a short-term exacerbation of cardiovascular disease by
      ambient particle concentrations but also a potential role of particles in
      defining patients' vulnerability to acute coronary events. While this concept is
      consistent with the current understanding of the factors defining patients'
      vulnerability, the mechanisms and the time-scales on which the particle-induced
      vulnerability might operate are unknown.

PMID- 15990138
TI  - Risk assessment of DNA-reactive carcinogens in food.
AB  - Risk assessment of DNA-reactive carcinogens in food requires knowledge of the
      extent of DNA damage in the target organ which results from the competition
      between DNA adduct formation and repair. Estimates of DNA adduct levels can be
      made by direct measurement or indirectly as a consequence of their presence, for
      example, by tumor formation in animal models or exposed populations
      epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety
      of sources. They are generally not intrinsically DNA-reactive but require
      bioactivation to DNA-reactive metabolites a process which may be modulated by the
      compound itself or the presence of other xenobiotics. A single DNA reactant may
      form several distinct DNA adducts each undergoing different rates of repair. Some
      DNA reactants may be photochemically activated or produce reactive oxygen species
      and thus indirect oxidative DNA damage. The levels of DNA adducts arising from
      exposures influenced by variations in the doses, the frequency with which an
      individual is exposed, and rates of DNA repair for specific adducts. Each adduct
      has a characteristic efficiency with which it induces mutations. Based on
      experience with the well-studied DNA-reactive food carcinogen aflatoxin B(1)
      (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is
      considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent
      carcinogen, doses of <1.5 microg of unknown compounds are considered TDIs. Most
      DNA-reactants, including acrylamide, heterocyclic amines, and alpha,beta
      unsaturated carbonyl are below this value. Above that value, measurement of
      actual DNA adducts levels in either experimental animals with a risk assessment,
      or, when this occurs, exposed humans are needed. A number of approaches to
      undertake this are described including immunological, mass spectrometric and
      (32)P-postlabeling or the use of surrogates such as hemoglobin adducts, together
      with approaches to evaluate the results. A discussion of approaches to estimating
      possible threshold effects for DNA-reactive carcinogens is made.

PMID- 15990139
TI  - Derivation of a chemical-specific adjustment factor (CSAF) for use in the
      assessment of risk from chronic exposure to ethylene glycol: application of
      International Programme for Chemical Safety guidelines.
AB  - The International Programme for Chemical Safety (IPCS) has developed a set of
      guidelines ("the Guidance") for the establishment of Chemical-Specific Adjustment
      Factors (CSAFs) for in the assessment of toxicity risk to the human population as
      a result of chemical exposure. The development of case studies is encouraged in
      the Guidance document and comments on them have been encouraged by the IPCS. One
      provision in the Guidance is for the determination of CSAFs based on human data.
      We present a case study of the use of the Guidance for the determination of the
      CSAF for ethylene glycol (EG) primarily utilizing clinically obtained data. The
      most relevant endpoint for this analysis was deemed to be acute renal injury.
      These data were applied based on an assessment of the known pharmaco/toxico
      kinetic properties of EG. Because of the lack of both bioaccumulation of EG and
      reports of chronic or progressive renal injury from EG, it was concluded that the
      most appropriate model of chronic exposure is one of repeated acute episodes. The
      most relevant exposure metric was determined to be plasma glycolate
      concentration. Based on a prospective human study of EG-poisoned patients, the
      NOAEL for glycolate was found to be 10.1 mM. This value is similar to that
      obtained from animal data. The application of the Guidelines to this data
      resulted in a CSAF of 10.24, corresponding to a daily EG dose of 43.7 mg/kg/day.
      In 2000, Health Canada (HC) produced an animal data-based analysis of the maximum
      tolerated dose of EG. The results of our analysis are compared with those of HC,
      and the strengths and weaknesses of these two data types related to EG are
      discussed.

PMID- 15990140
TI  - Positron emission tomography in the quantification of cellular and biochemical
      responses to intrapulmonary particulates.
AB  - Inhaled mineral dusts and fibres can cause chronic pulmonary inflammation, often
      leading to permanent scarring with loss of function, but the mechanisms involved
      remain obscure. There are currently no good methods for monitoring inflammatory
      processes in situ. Positron emission tomography (PET) of suitable intravenously
      injected radiolabelled markers provides non-invasive and repeatable methods of
      quantifying biochemical and cellular responses. We have developed animal models
      of fibrotic and non-fibrotic pulmonary response to particulate instillation and
      characterised these by histology. Different components of the inflammatory
      response have been investigated by PET: (1) [(18)F]-labelled fluoro-deoxyglucose,
      a positron emitting glucose analogue, accumulates in cells in proportion to their
      glucose uptake; ex vivo microautoradiography indicates that neutrophils are the
      cells responsible for an increased signal during pulmonary inflammation; a
      persistently high uptake is associated with lung scarring. (2) The radioligand
      [(11)C]-R-PK11195 binds to benzodiazepine-like receptors abundant in macrophages;
      following particulate instillation, the [(11)C]-R-PK11195 PET signal tracks with
      lung macrophage accumulation and also localises to regions consistent with
      macrophage clearance; poor macrophage clearance is associated with fibrosis. (3)
      [(18)F]-fluoroproline is likely a substrate for extracellular matrix production,
      especially proline-rich collagen; during active scarring, the rate of lung uptake
      of fluoroproline is elevated. Localisation of radioactivity in the lung has been
      validated ex vivo by microautoradiography of tritium analogues of each of the
      positron emitting tracers. The use of PET to monitor different inflammatory
      processes by repeated scanning of the same animal or individual is helping to
      identify key events in the fibrotic process.

PMID- 15990141
TI  - Is marihuana [THC] anti-carcinogenic?

PMID- 15990142
TI  - Role of endogenous channels in red blood cells response to their exposure to the
      pore forming toxin Sticholysin II.
AB  - Sticholysin II (St II) is a highly hemolytic cytolysin isolated from the sea
      anemone Stichodactyla heliantus. The toxin hemolytic action takes place through
      the formation of channels that provoke an electrolyte unbalance leading to
      osmotic shock. The lytic event must involve the exchange of electrolytes and the
      entrance of water, leading to red blood cell disruption. These processes can
      occur through St II pores and/or the endogenous red blood cells transporters. In
      order to evaluate the contribution of these channels to water, anion and cation
      transport, we have measured the hemolysis and K+ efflux rates in the presence of
      several specific inhibitors. The results obtained in the presence of Hg, an AQP1
      blocker, indicate that water transport through these channels is not essential
      for the occurrence of the lytic process induced by St II. The data also support a
      partial role of K+ and anion transporters. In particular, they are compatible
      with a preferential K+ efflux though the K(+)/Cl- co-transport as a response to
      the promoted swelling. Furthermore, they suggest that chloride influx, a process
      that can regulate both K+ efflux and lysis, is partially mediated by the
      endogenous cell transporters, in particular, band-3 anion exchange system being
      relevant at early stages of the lytic process.

PMID- 15990143
TI  - A high proportion of Baltic Sea benthic cyanobacterial isolates contain
      apoptogens able to induce rapid death of isolated rat hepatocytes.
AB  - To assess the potential hepatotoxicity of benthic cyanobacteria, we isolated 41
      strains from the Baltic Sea. The bacteria were differentially extracted with
      solvents of decreasing polarity. The extracts were tested for ability to induce
      death of primary rat hepatocytes in suspension culture. Mainly morphological
      criteria were used to discriminate between cell death with apoptotic features
      (shrinkage, chromatin hypercondensation, budding) or necrotic features (swelling,
      loss of plasma membrane integrity). The 24 isolates containing hepatotoxic
      compounds were of the genus Anabaena. The non-toxic isolates were mainly Nostoc
      and Calothrix. The toxicity was not due to the known hepatotoxic cyanobacterial
      protein phosphatase inhibitors microcystin or nodularin, as demonstrated by
      lacking competition with microcystin for PP2A binding. Apoptotic cell death was
      rapid, being evident from 10 to 60 min after the addition of extract. Sometimes
      the initial apoptosis was followed by secondary necrosis. Three cyanobacterial
      extracts produced apoptosis with unusual cell morphology including actin
      rearrangements. It will be of interest to know if they contain substance(s)
      acting through novel death pathways. We conclude that benthic Anabaena
      cyanobacteria represent a rich source of apoptogenic toxins, presumably directed
      against competitors or predators in the aquatic environment, but obviously able
      also to induce cell death in mammalian parenchymal liver cells.

PMID- 15990144
TI  - Ichthyotoxicity caused by marine cone snail venoms?
AB  - Ten venoms from marine cone snails were tested for ichthyotoxic effects on zebra
      fish (Brachydanio rerio) when added to the water. Only two venoms, from Conus
      capitaneus and Conus episcopatus, produced lethal effects at high concentrations
      (50-300 microg/ml) within 20-90 min. No sedative or hypnotic symptoms were
      observed. The experiments confirm that Conus venoms exert a quick and prompt
      activity only by parenteral injection into the prey as it is performed by the
      snail.

PMID- 15990145
TI  - Use of artificial neural networks to evaluate the effectiveness of riverbank
      filtration.
AB  - Riverbank filtration (RBF) is a low-cost water treatment technology in which
      surface water contaminants are removed or degraded as the infiltrating water
      moves from the river/lake to the pumping wells. The removal or degradation of
      contaminants is a combination of physicochemical and biological processes. This
      paper illustrates the development and application of three types of artificial
      neural networks (ANNs) to estimate the effectiveness of two RBF facilities in the
      US. The feed-forward back-propagation network (BPN) and radial basis function
      network (RBFN) model prediction results produced excellent agreement with
      measured data at a correlation coefficient above 0.99 for filtrate water quality
      parameters, including temperature as well as turbidity, heterotrophic bacteria,
      and coliform removal. In comparison, the fuzzy inference system network (FISN)
      predicted only temperature and bacteria removal with reasonable accuracy. It is
      shown that the predictive performances of the ANNs depend on the model structure
      and model inputs.

PMID- 15990146
TI  - A soil alteration index based on phospholipid fatty acids.
AB  - Phospholipid fatty acid (PLFA) analysis has gained great importance in the study
      of soil microbial community structure. This structure can give indication of the
      soil status. Purpose of the present paper is to analyse PLFA patterns in altered
      agricultural soils in order to develop a soil status alteration index. Soils
      subjected either to intensive agricultural exploitation, or to overflow by
      municipal and industrial wastes, or to irrigation with saline waters were
      analysed for PLFA content and compared to adjacent untreated soils by means of
      different statistical techniques. Principal component analysis separated PLFAs in
      three groups: unsaturated PLFAs (first axis, 48% of total variance),
      monounsaturated and cyclopropane PLFAs (second axis, 28% of total variance) and
      polyunsaturated PLFAs (third axis, 24% of total variance). By means of canonical
      discriminant analysis, a soil alteration index (SAI) was produced from 15 PLFAs
      using two data sets. A third data set was used to test the SAI general validity
      together with other data sets reported in literature. The index validity was
      confirmed in most cases: SAI gave higher scores for control soils and was
      generally able to classify soils according to their reported degree of
      alteration.

PMID- 15990147
TI  - Adsorption and desorption characteristics of hydrophobic pesticide endosulfan in
      four Indian soils.
AB  - Adsorption and desorption characteristics of endosulfan in four Indian soils were
      studied extensively. The soils used were clayey soil (CL--lean clay with sand),
      red soil (GM--silty gravel with sand), sandy soil (SM--silty sand with gravel)
      and composted soil (PT--peat) as per ASTM (American Society for Testing and
      Materials) standards. Adsorption and desorption rates were calculated from
      kinetic studies. These values varied for alpha and beta endosulfan depending on
      the soil type. Maximum specific adsorption capacities (qmax) for different soils
      were calculated by Langmuir model. The values varied from 0.1 to 0.45 mg g(-1)
      for alpha endosulfan and 0.0942-0.2722 mg g(-1) for beta endosulfan. Maximum
      adsorption took place in clay soil followed by composted soil and red soil.
      Adsorptions of alpha and beta endosulfan were negligible in sand. The binding
      characteristics of various functional groups were calculated using Scatchard
      plot. Effect of functional groups was more predominant in clayey soil. Organic
      matter also played a significant role in adsorption and desorption of endosulfan.
      Endosulfan adsorption decreased drastically in clay soil when the pH was reduced.
      Desorption was higher at both acidic and alkaline pH ranges compared to neutral
      pH. Results indicated that alpha endosulfan is more mobile compared to beta
      endosulfan and mobility of endosulfan is maximum in sandy soil followed by red
      soil. It can be inferred that crystal lattice of the clay soil plays a
      significant role in endosulfan adsorption and desorption. Immobilization of
      endosulfan is more advisable in clay soil whereas biological and or chemical
      process can be applied effectively for the remediation of other soil types.

PMID- 15990148
TI  - Investigation of evaporation and biodegradation of fuel spills in Antarctica. I.
      A chemical approach using GC-FID.
AB  - Little effort has been devoted to differentiating between hydrocarbon losses
      through evaporation and biodegradation in treatability studies of fuel
      contaminated Antarctic soils. When natural attenuation is being considered as a
      treatment option, it is important to be able to identify the mechanism of
      hydrocarbon loss and demonstrate that rates of degradation are sufficient to
      prevent off-site migration. Similarly, where complex thermally enhanced
      bioremediation schemes involve nutrient addition, water management, air stripping
      and active heating, it is important to appreciate the relative roles of these
      mechanisms for cost minimisation. Following the loss of hydrocarbons by
      documenting changes in total petroleum hydrocarbons offers little insight into
      the relative contribution of evaporation and biodegradation. We present a
      methodology here that allows identification and quantification of evaporative
      losses of diesel range organics at a range of temperatures using successively
      less volatile compounds as fractionation markers. We also present data that
      supports the general utility of so-called biodegradation indices for tracking
      biodegradation progress. We are also able to show that at 4 degrees C indigenous
      Antarctic soil bacteria degrade Special Antarctic Blend fuel components in the
      following order: naphthalene and methyl-napthalenes, light n-alkanes, then
      progressively heavier n-alkanes; whereas isoprenoids and the unresolved complex
      mixture are relatively recalcitrant.

PMID- 15990149
TI  - Effects of increased sea water concentrations of CO2 on growth of the bivalve
      Mytilus edulis L.
AB  - It has been proposed that emission of anthropogenic carbon dioxide to the
      atmosphere will lead to increased concentrations of CO(2) in sea water
      corresponding to a decrease of pH of several tenths of pH units. An experiment
      was performed to test the effects of increased sea water concentrations of CO(2)
      on shell growth of the blue mussel Mytilus edulis. The experiment was performed
      in aquaria continuously flushed with sea water spiked with CO(2) to provide five
      different levels of pH between 6.7 and control sea water with a pH of 8.1. The
      shell length of the mussels was measured at the start and end of the 44 days
      experimental period. No mortality was observed during the first 23 days of the
      experiment. The growth increment in mm was much larger for small mussels than for
      large mussels, but relative growth profile as function of pH was more similar in
      the two size groups; observed differences may be random variation between
      samples. The experiments showed that CO(2) induced reduction of pH affects the
      growth of M. edulis negatively. There was a strong and statistically significant
      decrease in growth at the lowest pH values, with virtually no growth at pH = 6.7
      and reduced growth at pH = 7.1. The effect seems to set in between pH 7.4 and
      7.1; at mean pH levels 7.4 and 7.6 the growth increments were not significantly
      different from growth at normal pH 8.1.

PMID- 15990150
TI  - QSPR to aqueous solubility (lgSw) of alkyl(1-phenylsulfonyl) cycloalkane
      carboxylates using MLSER model and ab initio.
AB  - Based on the modified linear solvation energy relationship (MLSER) model and
      quantum chemical descriptors computed at HF/STO-3G, HF/LANL2DZ, B3LYP/LANL2D and
      B3LYP/6-31G* levels, different quantitative structure-property relationships
      (QSPRs) to the aqueous solubility (lgSw) of 28 alkyl(1-phenylsulfonyl)
      cycloalkane-carboxylates were obtained. It is suggested that the eight models
      developed in the present study all have good correlation and relatively small
      error, in which the model with four variables, the most positive formal charge
      (qH+), molecular volume (Vi), melting point (mp) and free energy (G0) as
      descriptors obtained from B3LYP/6-31G* level, exhibited the best optimum
      correlation (r2=0.9743 and q2=0.9644, respectively) and smallest error, and thus
      are advantageous to other models. It was also found that molecular volume is the
      most significant factor influencing lgSw. The lgSw increased with increasing qH+
      and G0, while decreased with increasing Vi and mp. The MLSER model achieved from
      ab initio calculation is better than that from the semiempirical AM1 method.

PMID- 15990151
TI  - Guidelines for routine mercury speciation analysis in seafood by gas
      chromatography coupled to a home-modified AFS detector. Application to the
      Andalusian coast (south Spain).
AB  - A home-modified atomic fluorescence detector (mAFS) has been employed for mercury
      and methylmercury determination in bivalves from the Andalusian coast (south
      Spain). This modification consists on the inclusion of a quartz flow cell into
      the detector, which increases the concentration of mercury atoms in the detector
      and therefore enhances sensitivity about two fold. Two analytical approaches for
      mercury speciation based on the coupling of gas chromatography on-line pyrolysis
      and mAFS (GC-Pyro-mAFS) have been tested. The first approach (Method 1) is based
      on aqueous ethylation followed by extraction into an organic solvent, and the
      second one (Method 2) in the extraction of monoalkylated mercury as chloride.
      Method 1 is a rapid procedure but not sensitive enough for the analysis of
      methylmercury in non-polluted sites (detection limit: 20 ng g(-1) as mercury, wet
      basis). The second one is quite more sensitive (detection limit: 0.2 ng g(-1),
      wet weight), but sample treatment is cumbersome and time-consuming. The optimum
      range for mercury determination for both methods are complementary and exhibit an
      overlapping measurable concentration range (OMCR) in which methylmercury can be
      indistinctly determined (75-100 ng g(-1) as mercury, wet basis). The suitability
      of both methods has been assayed with spiking experiences at levels within the
      OMCR with good recoveries. Both approaches have been validated with two certified
      reference materials (BCR-463, mercury and methylmercury in tuna fish; and NIST
      2977, organic contaminants and trace metals in mussel tissue). Both procedures
      have been used for the analysis of three species of bivalve molluscs collected
      along the Andalusian coast (south Spain), all of them employed for human
      consumption (Chamelea gallina, Donax trunculus and Scrobicularia plana), and
      their potential use in routine analysis has been established.

PMID- 15990152
TI  - Simultaneous heavy metal removal mechanism by dead macrophytes.
AB  - The use of dead, dried aquatic plants, for water removal of metals derived from
      industrial activities as a simple biosorbent material has been increasing in the
      last years. The mechanism of simultaneous metal removal (Cd2+, Ni2+, Cu2+, Zn2+
      and Pb2+) by 3 macrophytes biomass (Spirodela intermedia, Lemna minor and Pistia
      stratiotes) was investigated. L. minor biomass presented the highest mean removal
      percentage and P. stratiotes the lowest for all metals tested. Pb2+ and Cd2+ were
      more efficiently removed by the three of them. The simultaneous metal sorption
      data were analysed according to Langmuir and Freundlich isotherms. Data fitted
      the Langmuir model only for Ni and Cd, but Freundlich isotherm for all metals
      tested, as it was expected. The K(F) values showed that Pb was the metal more
      efficiently removed from water solution. The adsorption process for the three
      species studied followed first order kinetics. The mechanism involved in
      biosorption resulted ion exchange between monovalent metals as counter ions
      present in the macrophytes biomass and heavy metal ions and protons taken up from
      water. No significant differences were observed in the metal exchange amounts
      while using multi-metal or individual metal solutions.

PMID- 15990153
TI  - Particulate carbon measurements in California's San Joaquin Valley.
AB  - Aerosol carbon sampling methods and biases were evaluated during the California
      Regional PM10/PM2.5 Air Quality Study (CRPAQS) and Fresno Supersite programs.
      PM2.5 sampling was conducted using Desert Research Institute (DRI) sequential
      filter samplers (SFS) from December 1999 through February 2001 at two urban sites
      (Fresno and Bakersfield), one regional transport site (Angiola), and two boundary
      sites (Bethel Island and Sierra Nevada Foothills) during CRPAQS in the San
      Joaquin Valley (SJV). Additional filter-based sampling was done in Fresno as part
      of the US Environmental Protection Agency (EPA) Supersites program. Organic
      carbon (OC) and elemental carbon (EC) concentrations were higher during winter
      (December-February) than summer (June-August) and this trend was most pronounced
      at Fresno and Bakersfield. OC and EC displayed similar diurnal trends during
      winter and summer at Fresno and during winter at Angiola. The diurnal pattern at
      Angiola reflected the transport of secondary pollutants to the site. Collocated
      measurements of OC and EC on undenuded quartz-fiber filters were made at Fresno
      with the DRI SFS and the Andersen FRM and RAAS samplers. All average differences
      in OC between samplers were less than their respective measurement uncertainties.
      Positive and negative OC biases were evaluated at Fresno using the Andersen RAAS
      sampler with carbon-denuded and undenuded channels with Teflon-membrane and
      quartz-fiber filter pairs. Differences between the denuded particle OC and that
      obtained by subtracting the quartz-behind-Teflon or quartz-behind-quartz OC from
      the undenuded quartz-fiber front filter were less than twice their measurement
      uncertainties in most cases. Particulate OC in the denuded channel agreed most
      closely with the difference between undenuded front and backup quartz-fiber OC.

PMID- 15990154
TI  - Characterization of polycyclic aromatic hydrocarbons (PAHs) on lime spray dryer
      (LSD) ash using different extraction methods.
AB  - In this study, traditional Soxhlet, automatic Soxhlet and ultrasonic extraction
      techniques were employed to determine the speciation and concentration of
      polycyclic aromatic hydrocarbons (PAHs) on lime spray dryer (LSD) ash samples
      collected from the baghouse of a spreader stoker boiler. To test the efficiencies
      of different extraction methods, LSD ash samples were doped with a mixture of 16
      US EPA specified PAHs to measure the matrix spike recoveries. The results showed
      that the spike recoveries of PAHs were different using these three extraction
      methods with dichloromethane (DCM) as the solvent. Traditional Soxhlet extraction
      achieved slightly higher recoveries than automatic Soxhlet and ultrasonic
      extraction. Different solvents including toluene, DCM:acetone (1:1 V/V) and
      hexane:acetone (1:1 V/V) were further examined to optimize the recovery using
      ultrasonic extraction. Toluene achieved the highest spike recoveries of PAHs at a
      spike level of 10 microg kg(-1). When the spike level was increased to 50 microg
      kg(-1), the spike recoveries of PAHs also correspondingly increased. Although the
      type and concentration of PAHs detected on LSD ash samples by different
      extraction methods varied, the concentration of each detected PAH was
      consistently low, at microg kg(-1) levels.

PMID- 15990155
TI  - Partitioning of mono- and polycyclic aromatic hydrocarbons in a river sediment
      adjacent to a former manufactured gas plant site.
AB  - The equilibrium distributions, between water and coal-tar contaminated sediment,
      of 16 monocyclic and polycyclic aromatic hydrocarbons were measured and evaluated
      for consistency with a Raoult's Law-based quantitative relationship. The
      quantitative relationship calculates the pore water concentration as the product
      of the aqueous solubility (or for compounds that are solid at room temperature,
      the aqueous super-cooled liquid solubility) and the mole fraction concentration
      of the compound within the liquid coal tar. Sediment was collected at five
      locations at two depths within a 120 m stretch of a river adjacent to a former
      manufactured gas plant, and all samples contained non-aqueous phase liquid (NAPL)
      coal tar. Although the amount of coal tar varied between samples by over an order
      of magnitude, the Raoult's Law-based NAPL-water partition coefficients for each
      monocyclic or 2- or 3-ring polycyclic aromatic hydrocarbon measured in this study
      generally varied within a factor of 2 over all sediments.

PMID- 15990156
TI  - Variations of nanoparticle concentrations at the Fresno Supersite.
AB  - Particle size distributions from 3 nm to 2 mum were measured at the Fresno, CA,
      Supersite from August 25, 2002 through July 31, 2003. Nanoparticle (3-10 nm)
      concentrations and the ratio of nanoparticle to total particle concentration were
      inversely related to particle surface areas from 50 to 1000 mum(2) cm(-3).
      Elevated nanoparticle concentrations were associated with motor vehicle emissions
      and with photochemical particle production. In contrast with Atlanta, GA, where
      concentrations of photochemically derived nanoparticles exceeded 10(5) cm(-3), 5
      min average nanoparticle concentrations in Fresno never exceeded 24,400 cm(-3).
      While photochemical particle production occurs in Fresno, evidence of new
      particle production (i.e., an increase in number concentration with decreasing
      size below 10 nm) was not observed. This suggests that photochemical particle
      production may have occurred at a higher altitude followed by mixing to the
      surface, or that the fresh particle production rate was smaller with respect to
      the loss rate by coagulation than it was in Atlanta. Lower production rates in
      Fresno are more consistent with lower concentrations of sulfur precurors and low
      relative humidity in Fresno than they are in Atlanta.

PMID- 15990157
TI  - Environmental impact from mountainous olive orchards under different soil
      management systems (SE Spain).
AB  - Soil erosion, runoff and nutrient-loss patterns over a two-year period (1999
      2000) were monitored in erosion plots on a mountainside with olive (Olea europaea
      cv. Picual) trees under three different types of soil management: (1) non-tillage
      with barley (Hordeum vulgare) strips of 4 m width (BS); (2) conventional tillage
      (CT); (3) non-tillage without plant strips (NT). The erosion plots, located in
      Lanjaron (Alpujarras) on the southern flank of the Sierra Nevada Mountains in
      south-eastern Spain, had 30% slope at an altitude of 565 m and 192 m(2) (24x8 m)
      in area. The highest erosion and runoff values, ranging from 10.5 to 40.7 t ha(
      1) yr(-1) and from 26.5 to 51.5 mm yr(-1), respectively, over the entire study
      period, were measured under NT. In CT, erosion ranged from 1.0 to 10.4 t ha(-1)
      yr(-1) and runoff from 6.7 to 15.2 mm yr(-1), while under BS, erosion ranged from
      1.7 to 2.4 t ha(-1) yr(-1) and runoff from 19.6 to 20.0 mm yr(-1). It is
      concluded that the BS and CT reduced the soil erosion by 92% and 78%, with
      respect to the NT, and the runoff by 49% and 72%, respectively. The total NPK
      losses (sediments and runoff) from BS averaged 0.87, 0.07 and 0.72 kg ha(-1),
      from CT 1.82, 0.11 and 0.97 kg ha(-1) and from NT 3.15, 0.29 and 2.45 kg ha(-1),
      respectively. In addition, nutrient concentrations in the surface runoff were
      higher than the recommended level for standard water quality for N-NO(3), N-NH(4)
      and soluble P, particularly from NT and CT. These results support the
      recommendation of non-tillage with barley strips for sloped agricultural land in
      order to reduce erosion and pollution.

PMID- 15990158
TI  - Effects of sewage sludge on pH and plant availability of metals in oxidising
      sulphide mine tailings.
AB  - A field study was conducted adjacent to the tailings deposit of the Aitik copper
      mine in the north of Sweden to investigate the effects of sewage sludge on pH and
      plant availability of Al, Mn, Cu, Zn, Ni, Pb, As, Cr and Cd in the oxidising
      sulphide tailings. One treatment was supplied with sewage sludge, while the
      control received NPK-fertiliser. The tailings samples were collected at the
      beginning and the end of the growing season and extracted by NH(4)NO(3), NH(4)Ac
      EDTA and HNO(3). Plant tissue concentrations of the elements were determined in
      the above-ground parts of barley (Hordeum vulgare) and red fescue (Festuca
      rubra). The application of sewage sludge resulted in higher crop yields compared
      to the control, although the buffering capacity and the metal immobilising effect
      of the sludge were limited. The pH decreased from 6.6 to 4.3 in the control and
      from 6.4 to 4.8 in the sludge-treated tailings during the growing season,
      probably due to sulphide oxidation in the tailings. This resulted in increased
      levels of soluble elements in all treatments studied. Application of sewage
      sludge resulted in elevated levels of soluble Zn and lower values of soluble As
      and Cd in the unaltered tailings but increased levels of specifically adsorbed
      Cu, Ni and As in the oxidised tailings. This was partly reflected in the plants,
      as the application of sewage sludge resulted in 67 mg Zn kg(-1) in barley grains
      and 60 mg Zn kg(-1) in red fescue shoots, both values twice as high as the
      corresponding values in the control, but lower As contents in both straw (0.3 mg
      kg(-1)) and grain (0.06 mg kg(-1)) of barley compared to the control (0.6 and 0.2
      mg kg(-1), respectively). In addition, red fescue grown in sludge-treated plots
      contained significantly higher levels of Al, Cu, Pb, As and Cr compared to the
      control. The levels of several metals in barley and red fescue grown in both
      treatments exceeded background values found in the literature. The Cu content in
      barley straw exceeded 100 mg kg(-1) in both treatments and might be toxic to
      grazing animals. Thus, this study suggests that adding sewage sludge to the mine
      tailings at Aitik would not counteract the effects of the sulphide oxidation in
      the tailings. Furthermore, using a sequential extraction technique proved
      preferable to using total metal analysis in order to predict plant uptake of the
      elements in the tailings.

PMID- 15990159
TI  - Development of a time-resolved immunofluorometric assay for quantifying platelet
      derived microparticles in human plasma.
AB  - Platelet-derived microparticles (PMPs) are considered a marker of platelet
      activation. They vary considerably in size, and flow cytometry, the predominant
      method used to assay PMPs, is only detecting larger PMPs (>0.1 microm). We
      describe here a method that quantifies the amount of PMP-located GPIIb antigen in
      detergent-treated platelet-free plasma (PPP) by means of a one-step time-resolved
      immunofluorometric assay (TR-IFMA). This assay uses a streptavidin-coated
      microwell plate and two different monoclonal antibodies to GPIIb (CD41), one
      conjugated to biotin and the other labeled with europium ion. A wide linear range
      standard curve with low background and a high sensitivity was obtained. Pre-assay
      ultracentrifugation or filtration of PPP extensively reduced the fluorometric
      signal, indicating that the GPIIb antigen is mainly particle-located. A strong
      correlation between the amount of GPIIb and PMP as detected by flow cytometry was
      found. Consequently, the assay can be used to study PMP-related phenomena and, in
      contrast to flow cytometry, can be used on frozen samples and is independent of
      PMP size.

PMID- 15990160
TI  - Thromboembolic complications in the nephrotic syndrome: pathophysiology and
      clinical management.
AB  - Patients with the nephrotic syndrome are at increased risk of developing venous
      and arterial thromboembolism, the most common of which is renal vein thrombosis.
      There are several unanswered or controversial issues relating to the nephrotic
      syndrome and thromboembolism, which include the mechanism of thromboembolism, and
      optimal diagnostic and anticoagulant management strategies. This review will
      discuss several of these issues: the epidemiology and clinical spectrum of
      thromboembolic disease occurring in patients with the nephrotic syndrome; the
      pathophysiology of the hypercoagulable state associated with the nephrotic
      syndrome; the diagnosis of renal vein thrombosis in the nephrotic syndrome; and
      the evidence for prophylactic and therapeutic anticoagulation strategies in such
      patients.

PMID- 15990161
TI  - Ovarian cancer and venous thromboembolic risk.
AB  - OBJECTIVE: To determine the incidence and the prognostic factors of objectively
      diagnosed deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with
      epithelial ovarian malignancy. METHODS: We reviewed the records of all patients
      with epithelial ovarian cancer who were diagnosed, treated, and followed-up at
      our institution between 1990 and 2001. Data were collected regarding age, body
      mass index, previous DVT and PE, menopause status, FIGO stage, grade, histology,
      type of surgery, residual disease, first line chemotherapy, and relapse status.
      RESULTS: Of the 253 cases, the overall incidence of symptomatic venous
      thromboembolic events (VTE) was 16.6% (42 patients): 1.6% (4) with PE and 15%
      (38) with DVT. 8 events (3.2%) were detected before tumor diagnosis, 6 (2.4%) in
      the postoperative period, 16 (6.4%) during first line chemotherapy and 12 (4.8%)
      throughout the follow-up period. Risk factors associated with occurrence of VTE
      were: at diagnosis, history of deep vein thrombosis (P = 0.001); during
      chemotherapy, older age (P = 0.017), larger body mass index (P = 0.019), FIGO
      stage 2c-4 (P = 0.004), no surgery (P = 0.003), and presence of residual tumor (P
      = 0.026). None of the considered risk factors were found to be predictors of VTE
      postoperatively. The multivariate regression analysis found that residual tumor,
      age, and body mass index were independent prognostic factors. CONCLUSION: The
      incidence of VTE throughout the entire history of ovarian malignancy is high.
      Prognostic factors could be used to establish prophylaxis protocols based on risk
      stratification.

PMID- 15990162
TI  - Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of
      cervical cancer in Japanese subjects.
AB  - OBJECTIVE: In this study, genetic polymorphisms, XRCC1 Arg399Gln and OGG1
      Ser326Cys were examined with reference to cervical cancer risk in a population
      based incident case-control study in Japan. METHODS: The cases comprised 131
      cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with
      adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled
      from 320 healthy women who underwent a health checkup. RESULTS: The frequency of
      the XRCC1 399GlnGln genotype was higher in individuals with
      adenocarcinoma/adenosquamous carcinoma than in the healthy controls (OR = 2.98,
      95% CI = 1.11-8.01, P = 0.030). However, no association was demonstrated in SCC.
      Analysis of OGG1 Ser326Cys polymorphism showed no significant differences between
      cervical cancer patients and controls. In stratification analysis, significant
      elevated risk of adenocarcinoma/adenosquamous carcinoma was associated with the
      XRCC1 399GlnGln genotype among nonsmokers (OR = 3.85, 95% CI = 1.28-11.59, P =
      0.017), but not among smokers. No gene-gene interaction was observed in our case
      subjects. CONCLUSION: This is the first report that the XRCC1 Arg399Gln
      polymorphism might be important in relation to the risk of
      adenocarcinoma/adenosquamous carcinoma of the cervix.

PMID- 15990163
TI  - Synthesis and photopolymerization of low shrinkage methacrylate monomers
      containing bulky substituent groups.
AB  - OBJECTIVES: This study was conducted to determine whether novel
      photopolymerizable formulations based on dimethacrylate monomers with bulky
      substituent groups could provide low polymerization shrinkage without sacrifice
      to degree of conversion, and mechanical properties of the polymers. METHODS:
      Relatively high molecular weight dimethacrylate monomers were prepared from rigid
      bisphenol A core groups. Photopolymerization kinetics and shrinkage as well as
      flexural strength and glass transition temperatures were evaluated for various
      comonomer compositions. RESULTS: Copolymerization of the bulky monomers with
      TEGDMA show higher conversion but similar shrinkage compared with Bis-GMA/TEGDMA
      controls. The resulting polymers have suitable mechanical strength properties for
      potential dental restorative materials applications. When copolymerized with
      PEGDMA, the bulky monomers show lower shrinkage, comparable conversion, and more
      homogeneous polymeric network structures compared with Bis-EMA/PEGDMA systems.
      SIGNIFICANCE: The novel dimethacrylate monomers with reduced reactive group
      densities can decrease the polymerization shrinkage as anticipated, but there is
      no significant evidence that the bulky substituent groups have any additional
      effect on reducing shrinkage based on the physical interactions as polymer side
      chains. The bulky groups improve the double bond conversion and help maintain the
      mechanical properties of the resulting polymer, which would otherwise decrease
      rapidly due to the reduced crosslinking density. Further, it was found that bulky
      monomers help produce more homogeneous copolymer networks.

PMID- 15990164
TI  - Mylar and Teflon-AF as cell culture substrates for studying endothelial cell
      adhesion.
AB  - The textured and opaque nature of Dacron and ePTFE has prevented the use of these
      fabrics in conventional cell culture techniques normally employed to optimize
      cell attachment and retention. This lack of optimization has led, in part, to the
      poor performance of endothelialization strategies for improving vascular graft
      patency. Here we show that thin, transparent films of Mylar and Teflon-AF are
      viable in vitro cell culture mimics of Dacron and ePTFE vascular graft materials,
      particularly for the study of protein mediated endothelial cell (EC) attachment,
      spreading and adhesion. Glass substrates were used as controls. X-ray
      photoelectron spectroscopy (XPS) and contact angle analysis showed that Mylar and
      Teflon-AF have surface chemistries that closely match Dacron and ePTFE. (125)I
      radiolabeling was used to quantify fibronectin (FN) adsorption, and FN and
      biotinylated-BSA "dual ligand" co-adsorption onto glass, Mylar and Teflon-AF
      substrates. Native human umbilical vein endothelial cells (HUVEC) and
      streptavidin-incubated biotinylated-HUVEC (SA-b-HUVEC) spreading was measured
      using phase contrast microscopy. Cell retention and adhesion was determined using
      phase contrast microscopy under laminar flow. All surfaces lacking protein pre
      treatment, regardless of surface type, showed the lowest degree of cell spreading
      and retention. Dual ligand treated Mylar films showed significantly greater SA-b
      HUVEC spreading up to 2 h, but were similar to HUVEC on FN treated Mylar at
      longer times; whereas SA-b-HUVEC spreading on dual ligand treated Teflon-AF was
      never significantly different from HUVEC on FN treated Teflon-AF at any time
      point. SA-b-HUVEC retention was significantly greater on dual ligand treated
      Mylar compared to HUVEC on FN treated Mylar over the entire range of shear
      stresses tested (3.54-28.3 dynes/cm(2)); whereas SA-b-HUVEC retention to dual
      ligand and HUVEC retention to FN treated Teflon-AF gave similar results at each
      shear stress, with only the mid-range of stresses showing significant difference
      in cell retention to Teflon-AF.

PMID- 15990165
TI  - Role of maternal dietary antioxidant supplementation in murine placental and
      fetal limb development.
AB  - Methylnitrosourea (MNU) is a multisystem teratogen that damages proliferating
      cells through macromolecule alkylation and generation of reactive oxygen species
      (ROS). Murine dams exposed to MNU midgestation produce offspring with distal limb
      malformations, an outcome reduced by maternal immune stimulation.
      Immunostimulatory effects of antioxidant therapy may in part explain this
      improved birth outcome. The present study hypothesizes that placental, rather
      than fetal, damage from excessive ROS may contribute to MNU-induced embryopathy.
      Fetal limbs and placentas were examined in immunotolerant CD-1 and
      immunosensitive C57BL/6N mice exposed to MNU, dietary antioxidant butylated
      hydroxytoluene (BHT), or both. MNU increased fetal resorptions and incidence of
      syndactyly, oligodactyly, polydactyly, and interdigital webbing, and decreased
      fetal size in both mouse strains. BHT reduced syndactyly and oligodactyly in both
      strains, and reduced polydactyly in C57BL/6N mice. Increased webbing in MNU and
      MNU+BHT groups likely represented maturational delay. Placentas from CD-1 and
      C57BL/6N MNU-exposed dams demonstrated decreased trophoblasts and increased
      necrosis of endothelium. Similar to distal limb defects, placental damage was
      reduced in mice receiving MNU+BHT. These results suggest that placental damage
      and fetal defects caused by MNU are in part ROS-mediated, and reduced distal limb
      defects following MNU+BHT may be related to improved placental integrity and
      function.

PMID- 15990166
TI  - Elevation of both cyclooxygenase-2 and prostaglandin E2 receptor EP3 expressions
      in rat placenta after uterine artery ischemia-reperfusion.
AB  - Intrauterine growth restriction (IUGR) has a multifactorial pathogenesis and is
      an important cause of perinatal mortality. The relationship between fetal weight
      and placental blood flow in an animal model of IUGR has been investigated,
      showing that fetal growth is regulated by placental blood flow. The aim of the
      present study was to determine whether ischemia-reperfusion (I/R) injury
      stimulates the prostaglandin E2 (PGE2) system or the vascular endothelial growth
      factor (VEGF) system in the placenta of a rat IUGR model. COX-2 is reported to be
      involved in ischemic damage in many organs. There are 4 types of PGE2 receptor
      (EP1, EP2, EP3 and EP4). It is well known that EP1 and EP3 is associated with
      vasoconstriction. In the present study, vessels were occluded in the right
      uterine horn on day 17 of pregnancy in rats, and the clamps were removed after 30
      min of ischemia. At 24h, 48 h, and 5 days after I/R injury, the live fetuses and
      placentas were obtained by cesarean section. This study revealed that I/R injury
      caused IUGR 5 days after the treatment. COX-2 expression and EP3 receptor
      expression were significantly elevated at 24h after I/R injury, but VEGF mRNA
      expression was not altered in the placenta from the ischemic horn compared with
      the non-ischemic horn. These results suggested that induction of the COX-2-EP3
      system in the placenta may be one of the causes of IUGR induced by uterine
      ischemia, because the EP3 receptor and PGE2 are well known to mediate
      vasoconstriction in many organs.

PMID- 15990167
TI  - Suppression of extravillous trophoblast invasion of uterine spiral arteries by
      estrogen during early baboon pregnancy.
AB  - The present study determined whether estrogen plays a role in regulating invasion
      and remodeling of the uterine spiral arteries by extravillous trophoblasts during
      early baboon pregnancy. The level of trophoblast invasion of spiral arteries was
      assessed on day 60 of gestation (term is 184 days) in baboons untreated or
      treated on days 25-59 with estradiol or aromatizable androstenedione. The
      administration of estradiol or androstenedione increased (P<0.01) maternal serum
      estradiol levels approximately 3-fold above normal. The mean+/-SE percentage of
      spiral arteries/arterioles invaded by extravillous cytotrophoblasts in estradiol
      treated baboons for vessels with diameters of 26-50 microm (0.0+/-0.0), 51-100
      microm (1.2+/-0.7) and >100 microm (13.2+/-5.5) was 100%, 90%, and 75% lower
      (P<0.001), respectively, than in untreated baboons (2.4+/-1.2%; 11.0+/-5.5%, and
      54.5+/-8.5%, respectively). Similar results were obtained with androstenedione
      treatment. However, the distribution of uterine spiral arteries grouped by
      diameter or number of arteries per basal plate area, i.e. microvessel density,
      were similar in untreated and estrogen-treated baboons. We suggest, therefore,
      that the low levels of estrogen exhibited during early primate pregnancy are
      required to permit normal progression of trophoblast vascular invasion and that
      the surge in estrogen which occurs during the second-third of normal pregnancy
      has a physiological role in suppressing further arterial trophoblast invasion.
      Consequently, we propose that the estrogen-dependent restraint of spiral artery
      invasion/remodeling ensures optimal blood flow dynamics across the uteroplacental
      vascular bed to promote normal fetal growth and development.

PMID- 15990168
TI  - Assessing the performance of Hormosira banksii (Turner) Desicaine germination and
      growth assay using four reference toxicants.
AB  - This study evaluated the performance of a Hormosira banksii germination
      inhibition bioassay developed to assess the toxicity of single compounds and
      complex effluents in the Australasian region. The reproducibility of 48 and 72 h
      germination and growth toxicity tests was determined using four reference
      toxicants, namely, ammonia, copper, phenol and zinc. H. banksii spore germination
      and growth was significantly inhibited following exposure to each of the
      toxicants. H. banskii spores were most sensitive to ammonia and showed decreasing
      sensitivity to copper, zinc and phenol. The EC50 values ranged from 0.07 to 0.08
      mg L(-1) for ammonia, 0.09 to 0.22 mg L(-1) for copper, 36 to 1068 mg L(-1) for
      phenol and 19 to 23 mg L(-1) for zinc. Variability of the test method ranged from
      14% to 144% and was comparable to that observed for commonly employed bioassays
      against appropriate reference toxicants.

PMID- 15990169
TI  - Metal levels in sugar cane (Saccharum spp.) samples from an area under the
      influence of a municipal landfill and a medical waste treatment system in Brazil.
AB  - In July 2003, duplicated samples of roots, stems and leaves of sugar cane
      (Saccharum spp.) were collected in 25 points of an area under direct influence of
      the municipal landfill site (MLS) and medical waste treatment system (MWTS) of
      Ribeirao Preto, Sao Paulo, Brazil. Cadmium (Cd), chromium (Cr), copper (Cu),
      mercury (Hg), manganese (Mn), lead (Pb) and zinc (Zn) were determined by atomic
      absorption spectrophotometry. The following concentrations (mg/kg) were found in
      roots: Cd, 0.22+/-0.12; Cr, 64.3+/-48.7; Cu, 140.6+/-27.7; Hg, 0.04+/-0.02; Mn,
      561.6+/-283.3; Pb, 7.9+/-2.1 and Zn, 177.4+/-64.9. For some metals, these levels
      are higher than the concentrations previously reported for different plants,
      reaching, in some cases, values that might be considered toxic for vegetables.
      Metal levels in stems were 80-90% of those found in roots, while the
      concentrations detected in leaves were significantly lower than those in roots.
      The present results suggest that MLS and MWTS activities might have been
      increasing metal concentrations in edible tissues of sugar cane grown in the area
      under their influence. Moreover, the traditional agricultural practices in the
      production of sugar cane could be also another determinant factor to reach the
      current metal levels. The results of this study indicate that sugar cane is a
      crop that is able to grow in areas where metals in soils are accumulated.

PMID- 15990170
TI  - Water balance and nitrate leaching losses under intensive crop production with
      Ochric Aquic Cambosols in North China Plain.
AB  - A 2-year field experiment was conducted in an Ochric Aquic Cambosols on a 1-ha
      field with rotation of winter wheat-summer corn located in Fengqiu County in
      North China Plain from 1 October 1998 to 30 September 2000 to quantify water
      balance and evaluate soil water loss by deep drainage and nitrate loss by
      leaching out of the root zone under the current agricultural practices.
      Considerable deep drainage was found especially in 1999-2000, during which period
      up to 273.9 mm of water, accounting for 60.6% of total amount of irrigation and
      24.7% of total surface input (rainfall+irrigation), was lost by deep drainage.
      Even in both wheat cropping seasons when total amount of surface input was less
      than total actual evapotranspiration, 84.0 and 121.3 mm water was lost by
      drainage in 1999 and 2000, respectively. Soil NO3(-)-N was transported to deeper
      soil layers during the growing seasons and considerable amount of NO3(-)-N
      accumulated at 170 cm soil layer (the bottom of root zone) during the September
      October period (the harvest time of summer corn) every year. About 28.6 kg N ha-1
      was lost by leaching out of the root zone in 1998-1999 and 81.8 kg N ha-1 in 1999
      2000, accounting for 5.9% and 15.7% of total nitrogen (N) inputs, respectively.
      The significant deep drainage and nitrate leaching loss were attributed to
      excessive and inappropriate irrigation and nitrogen (N) fertilization, which may
      result in severe groundwater pollution if current agricultural managements are
      not changed.

PMID- 15990171
TI  - Historical change of heavy metals in urban soils of Nanjing, China during the
      past 20 centuries.
AB  - Two typical areas, including once commercial and residential quarters of Nanjing,
      China, were studied by investigating soil properties especially heavy metals of
      soils in various cultural layers formed in different Chinese Dynasties. The age
      of the soil profiles was dated by both archaeological and 14C chronological
      methods. The results showed that urban soils in the old commercial/workshop
      quarter of Nanjing were generally contaminated by heavy metals Cu, Zn, Pb, but
      their concentration levels varied significantly among the cultural layers formed
      in different dynasties. The substantial increase of heavy metals appeared in
      three historical periods, i.e., South Dynasty (222-589 AD), the earlier Ming
      (1368-1644 AD) and the late Qing (1644-1912 AD) in one area. The tremendous input
      and storage of heavy metals in soils was explained by the primitive smelting and
      the strengthened metal processing activities, which might be due to the
      requirement of weapon making or other industries, in the changing social
      conditions of the corresponding periods. Soils in the once noble political,
      cultural centers did not show significant increase of heavy metals. The
      difference in the distribution pattern of heavy metals revealed the contrasting
      history of the site uses. The change of contaminant level in soils is believed to
      be a reflection of various human activities in the city during the past 20
      centuries.

PMID- 15990172
TI  - Methylmercury alters Eph and ephrin expression during neuronal differentiation of
      P19 embryonal carcinoma cells.
AB  - Developmental exposure to methylmercury (MeHg) induces a spectrum of neurological
      impairment characterized by cognitive disturbance, sensory/motor deficit, and
      diffuse structural abnormalities of the brain. These alterations may arise from
      neural path-finding errors during brain development, resulting from disturbances
      in the function of morphoregulatory guidance molecules. The Eph family of
      tyrosine kinase receptors and their ligands, the ephrins, guide neuronal
      migration and neurite pathfinding mainly via repulsive intercellular
      interactions. The present study examined the effects of MeHg on mRNA and protein
      expression profiles of Ephs and ephrins in the P19 embryonal carcinoma (EC) cell
      line and its neuronal derivatives. Undifferentiated control P19 cells displayed
      low- to undetectable levels of mRNA for ephrins or Ephs, with the sole exception
      of EphA2 which was highly expressed. Upon differentiation into neurons, the
      ephrin expression increased progressively through day 10. Similarly, expression
      of the Ephs, including EphsA3, -A4, -A8, -B2, -B3, -B4, and -B6, increased
      significantly. In contrast, EphA2 expression decreased in day 2, 6 and 10 control
      neurons. Treatment with MeHg did not affect the expression of mRNA for ephrins or
      Ephs in undifferentiated P19 cells. However, treatment of differentiating neurons
      with MeHg for 24 h caused consistent increases in ligand mRNA expression,
      particularly ephrin-A5, -A6, -B1, and -B2. Similarly, MeHg induced variable
      increases in mRNA expression of receptors EphA2, -A3, -B3, and -B6. A trend
      toward a concentration-response relationship was observed for the alterations in
      Eph receptor mRNA expression although increases at the low and mid concentrations
      did not reach statistical significance. Immunoblots for ligand and receptor
      proteins mirrored the increases in the mRNA levels at the 0.5 and 1.5 microM MeHg
      concentrations but showed decreased protein levels compared to controls at the
      3.0 microM concentration. Alterations in the Eph/ephrin family of repulsion
      molecules may represent an important mechanism in developmental MeHg
      neurotoxicity.

PMID- 15990173
TI  - Molecular cloning and expression profile analysis of interleukin-10 and
      interleukin-18 cDNA of Indian water buffalo (Bubalus bubalis).
AB  - The cDNAs encoding the interleukin-10 and interleukin-18 of Indian water buffalo
      (Bubalus bubalis) were cloned and sequenced. A 537 bp IL-10 cDNA fragment and a
      623 bp IL-18 cDNA fragment were amplified by reverse transcriptase polymerase
      chain reaction (RT-PCR) from concanavalin A stimulated splenocytes. Sequence
      analysis of these cytokines revealed high level conservation at nucleic acid and
      protein level. Both these cytokines also showed strict conservation in the
      predicted secondary structure and critical amino acid residues compared to the
      ruminant homologues. Basal level expression of both IL-10 and IL-18 was observed
      in liver, lung and spleen. The expression level of IL-10 was not affected by
      mitogenic stimulation, whereas IL-18 was up regulated upon stimulation. The
      availability of these cytokine molecules will aid in the study of their role in
      the immunology and pathogenesis of infections in water buffalo.

PMID- 15990174
TI  - Hyaluronate receptor (CD44) and integrin alpha4 (CD49d) are up-regulated on T
      cells during MS relapses.
AB  - A longitudinal study of peripheral blood T cell adhesion molecule expression was
      performed in 24 relapsing-remitting MS patients. There were 15 relapses in 11
      patients during 15 months of observation. In comparison with remission,
      expression of hyaluronate receptor (CD44) was highly significant, and expression
      of integrin alpha4 (CD49d, VLA-4) significantly up-regulated during relapses.
      CD44 and CD49d are putative activity markers and CD44 a potential novel
      therapeutic target in MS.

PMID- 15990175
TI  - Reduction of blood pressure variability: a new strategy for the treatment of
      hypertension.
AB  - The main aims of the treatment of hypertension are to prevent end-organ damage
      (EOD) and to avoid consequent lethal complications associated with hypertension.
      Blood pressure level is a well-known determinant of EOD. However, recent studies
      suggest that blood pressure variability (BPV) is as important as blood pressure
      level in determining EOD. The reduction of BPV is an important contributory
      factor of the organ protection provided by some antihypertensive drugs. Thus,
      reduction of BPV might represent a new strategy for the treatment of
      hypertension.

PMID- 15990176
TI  - G-protein-coupled receptors encoded by human herpesviruses.
AB  - G-protein-coupled receptors (GPCRs) encoded by herpesviruses and poxviruses are
      homologous to mammalian chemokine receptors. GPCRs encoded by herpesvirus-6,
      herpesvirus-7, herpesvirus-8 and cytomegalovirus are among the best studied.
      Virally encoded GPCRs engage many different signal-transduction cascades, and
      have important roles in the life-cycles of the viruses and pathogenesis of human
      disease. Although signaling by these GPCRs might be modified by ligand binding,
      they often exhibit constitutive (basal) signaling activities that appear to
      provide selective advantages to the virus.

PMID- 15990177
TI  - Thioredoxin: friend or foe in human disease?
AB  - Thioredoxin (Trx), a small, ubiquitous thiol [sulfydryl (-SH)] protein, is one of
      the most important regulators of reduction-oxidation (redox) balance and, thus,
      redox-controlled cell functions. Although Trx was discovered 40 years ago in
      bacteria, the number and diversity of processes that Trx influences in human
      cells have only been appreciated recently. Processes influenced by Trx include
      the control of cellular redox balance, the promotion of cell growth, the
      inhibition of apoptosis and the modulation of inflammation. Not surprisingly, the
      role of Trx in a wide range of human diseases and conditions, including cancer,
      viral disease, ischaemia-reperfusion injury, cardiac conditions, aging, premature
      birth and newborn physiology, is subject to intense investigation. However,
      whether Trx contributes to or prevents the pathology of a particular condition is
      not always clear. In this article, we review the role of Trx in human disease and
      relate this to its redox activity and biological properties, and discuss the
      development and use of therapies that either inhibit or augment Trx activity.

PMID- 15990179
TI  - Cellular biomarkers of exposure and biological effect in hepatocytes of turbot
      (Scophthalmus maximus) exposed to Cd, Cu and Zn and after depuration.
AB  - Cellular biomarkers of exposure and biological effects were measured in
      hepatocytes of turbot exposed to either Cd, Cu or Zn at concentrations of 1 and
      10 mg/l seawater for 7 days and after depuration for 14 days. Metal content in
      hepatocyte lysosomes was determined by image analysis after autometallography
      (AMG) as volume density of autometallographed black silver deposits (Vv(BSD)).
      Metallothionein (MT) levels were quantified on liver sections by
      microdensitometry after immunohistochemical staining with a polyclonal anti cod
      MT antibody (MT-OD), and in the cytosolic fraction of hepatocytes by difference
      pulse polarography (MT-DPP). Lysosomal structural changes (lysosomal volume,
      surface and numerical densities--Vv(LYS), Sv(LYS) and Nv(LYS-), and surface-to
      volume ratio S/V(Lys)) were quantified by image analysis after demonstration of
      beta-glucuronidase activity on liver cryotome sections. Vacuolisation produced by
      metal-exposure in hepatocytes was quantified by stereology as volume density of
      vacuoles (Vv(VAC)). Exposure time and metal concentrations significantly affected
      Vv(BSD) in lysosomes, MT levels and the degree of vacuolisation after 1 h and 1
      day exposure to the three metals. The highest Vv(BSD), MT and Vv(VAC) values were
      recorded after 7 days exposure in all cases. MT-OD and MT-DPP were significantly
      correlated with Vv(BSD). Vv(LYS) in hepatocytes increased significantly after
      exposure to the metals. Exposure biomarkers returned to control values after
      depuration with the exception of those turbots that had been exposed to 10 mg
      Cd/l. Alike, Vv(LYS) and Sv(lys) (Cu exposure) and Nv(LYS) (Cd and Zn exposures)
      returned to control values after depuration. It has been therefore demonstrated
      that the biomarkers used are reversible and return towards control levels once
      metal exposure ceases. Overall, it is concluded that Vv(BSD), MT-levels and
      lysosomal responses are valuable biomarkers to assess metal exposure and its
      effects in turbot, although in quantitative terms the biomarker response varied
      between metals.

PMID- 15990178
TI  - Evidence for the involvement of central serotonergic mechanisms in cholinergic
      tremor induced by tacrine in Balb/c mice.
AB  - Tacrine is a potent and reversible inhibitor of acetylcholinesterase (AChE) in
      the brain. It produces tremor in animals, which is believed to be due to an
      increase in the brain acetylcholine level following AChE inhibition. The present
      study was undertaken to investigate the involvement, if any, of biogenic amines
      in the genesis of this motor dysfunction. Administration of tacrine (10-20 mg/kg,
      i.p.) produced dose- and time-dependent tremor in Balb/c mice. While in vivo
      inhibition of striatal AChE activity was observed only for the highest dose of
      tacrine, a dose-dependent increase in striatal choline acetyltransferase activity
      was obtained. Serotonin (5-HT) levels, as assayed following a sensitive HPLC
      electrochemical procedure, were significantly increased in nucleus caudatus
      putamen, nucleus accumbens, substantia nigra, nucleus raphe dorsalis, olivary
      nucleus and the cerebellum. However, dopamine or norepinephrine levels remained
      unaltered in these areas of the brain. In animals treated with p
      chlorophenylalanine, a specific tryptophan hydroxylase inhibitor and 5-HT
      depletor, tacrine failed to elevate the levels of 5-HT in the brain regions, and
      significantly attenuated tremor response to the drug. Tacrine-induced tremor was
      also significantly (83%) attenuated by 5-HT(2A/2C) receptor antagonist mianserin
      (5 mg/kg, i.p.), but methysergide (5 mg/kg, i.v.) could block tacrine-induced
      tremor only by 20%. Atropine (5 mg/kg, i.p.) antagonized tacrine-induced tremor
      by about 53%, but a combination of atropine and mianserin completely blocked the
      tremor response. These results indicate that the cholinergic tremor produced by
      tacrine in Balb/c mice is mediated via central serotonergic mechanisms, and
      stimulation of 5-HT(2A/2C) receptors plays a pivotal role in this motor
      dysfunction.

PMID- 15990180
TI  - The reticulocyte binding proteins of Plasmodium cynomolgi: a model system for
      studies of P. vivax.

PMID- 15990181
TI  - Identification of an Entamoeba histolytica gene encoding a protein disulfide
      isomerase that functionally complements the dsbA mutation in Escherichia coli.

PMID- 15990182
TI  - Comparison of antagonist activity of spantide family at human neurokinin
      receptors measured by aequorin luminescence-based functional calcium assay.
AB  - Neurokinin receptors (NK1, NK2, NK3) are G-protein-coupled receptors, which upon
      activation by a peptide agonist induce a transient increase in the concentration
      of intracellular calcium. The functional assay based on aequorin-derived
      luminescence triggered by receptor-mediated changes in Ca2+ levels was used to
      compare the effect of spantides I-III on SP-, NKA- and NKB-stimulated NK1, NK2
      and NK3 receptors, respectively. Recombinant cell lines expressing neurokinin
      receptors and apoaequorin were used in the study. The obtained results indicate
      that all three spantides acted as competitive antagonists at the NK1 and NK2
      receptors and inhibited agonist-induced calcium responses. The rank order of
      antagonism at the NK1 receptor was spantide II>spantide III>spantide I and at the
      NK2 receptor was spantide III>spantide II>spantide I. All three spantides failed
      to antagonize NKB-induced calcium responses at the NK3 receptor.

PMID- 15990183
TI  - Broad complex tachycardia during treatment of atrial fibrillation with a 1c
      antiarrhythmic drug: ventricular or supraventricular proarrhythmia?

PMID- 15990184
TI  - The importance of peer effects, cigarette prices and tobacco control policies for
      youth smoking behavior.
AB  - This paper expands the youth cigarette demand literature by undertaking an
      examination of the determinants of smoking among high school students
      incorporating the importance of peer effects and allowing cigarette prices
      (taxes) and tobacco control policies to have a direct effect and an indirect
      effect (via the peer effect) on smoking behavior. To control for the potential
      endogeneity of our school-based peer measure we implement a two-stage generalized
      least squares estimator for a dichotomous dependent variable and implement a
      series of diagnostic tests. The key finding is that peer effects play a
      significant role in youth smoking decisions: moving a high-school student from a
      school where no children smoke to a school where one quarter of the youths smoke
      is found to increase the probability that the youth smokes by about 14.5
      percentage points. The results suggest that there is a potential for social
      multiplier effects with respect to any exogenous change in cigarette taxes or
      tobacco control policies.

PMID- 15990185
TI  - On the aggregation of health status measures.
AB  - In the present paper, we address the problem of finding conditions under which
      aggregation of individual health status measurements (e.g. QALYs) is meaningful
      in the sense that there is a universal unit of measurement for health. The
      problem is studied in a model where different aspects of health take the form of
      Lancasterian characteristics to be produced by the individuals using commodities
      obtained in the market. For a meaningful unit of measurement to exist, marginal
      rates of substitution between different aspects of health should not differ among
      individuals, and for this to happen in an equilibrium of the economy considered,
      certain assumptions of separability (of technology and/or preferences) must be
      satisfied. This means that universal measures of health will be meaningful only
      if there are not too many spillovers in achieving different aspects of health.

PMID- 15990186
TI  - Phase-II study on stereotactic radiotherapy of locally advanced pancreatic
      carcinoma.
AB  - BACKGROUND AND PURPOSE: The majority of patients with pancreatic cancer have
      advanced disease at the time of diagnosis and are not amenable for surgery.
      Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with
      locally advanced disease. The effect of SRT was investigated in the present phase
      II trial. PATIENTS AND METHODS: Twenty-two patients with locally advanced and
      surgically non-resectable, histological proven pancreatic carcinoma were included
      into the trial. The patients were immobilized by the Elekta stereotactic body
      frame (SBF) or a custom made body frame. SRT was given on standard LINAC with
      standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days.
      RESULTS: Evaluation of response was found to be very difficult due to radiation
      and tumour related tissue reaction. Only two patients (9%) were found to have a
      partial response (PR), the remaining had no change (NC) or progression (PD) after
      treatment. Six patients had local tumour progression, but only one patient had an
      isolated local failure without simultaneous distant metastasis. Median time to
      local or distant progression was 4.8 months. Median survival time was 5.7 months
      and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days
      after treatment was pronounced. There was a significant deterioration of
      performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after
      14 days compared with base-line. However, 8 of 12 patients (66%) improved in
      performance status, scored less nausea, pain, or needed less analgesic drugs at 3
      months after treatment. Four patients suffered from severe mucositis or
      ulceration of the stomach or duodenum and one of the patients had a non-fatal
      ulcer perforation of the stomach. CONCLUSIONS: SRT was associated with poor
      outcome, unacceptable toxicity and questionable palliative effect and cannot be
      recommended for patients with advanced pancreatic carcinoma.

PMID- 15990187
TI  - A phase II study of localized prostate cancer treated to 75.6 Gy with 3D
      conformal radiotherapy.
AB  - BACKGROUND AND PURPOSE: To prospectively evaluate toxicity, biochemical failure
      free survival (bFFS) and biopsy-proven local control for prostate cancer patients
      treated with 75.6 Gy in 42 fractions using 6-field conformal radiotherapy to
      prostate alone. PATIENTS AND METHODS: From 1997 to 1999, 140 patients with T1
      2NxM0, Gleason score<or=8, and PSA<or=20 ng/ml prostate cancer were assessed
      using Radiation Therapy Oncology Group acute and late toxicity scores. bFFS was
      determined for 120 patients treated without hormones. Post-treatment prostate
      biopsies were performed at a median of 3 years and a late toxicity questionnaire
      was administered at a median of 5 years. RESULTS: Clinically important acute
      toxicities were gastrointestinal (GI) grade 2: 22% and 3: 0%, and genitourinary
      (GU) grade 2: 24% and 3: 2%. Late physician-assessed toxicities were GI>or=grade
      2: 2%, and GU>or=grade 2: 1%. The 3-year bFFS of patients failure-free before
      biopsy was 93% (95% CI: 83-100) from a negative biopsy and 22% (95% CI: 0-56)
      from a positive biopsy (P=0.001). Patients reported significantly more late
      toxicity than physicians (GI: P=0.003, GU: P<0.001). At 5.0 years median follow
      up, cause-specific survival was 98% (95% CI: 96-100), overall survival was 91%
      (95% CI: 86-97), and bFFS was 55% (95% CI: 45-64). CONCLUSIONS: 75.6 Gy caused
      modest levels of acute and late toxicity. Three-year biopsies predicted
      subsequent biochemical outcome.

PMID- 15990189
TI  - The alpha/beta ratio for prostate cancer: what is it, really?
AB  - Two recent studies of fractionated external beam radiotherapy in early prostate
      cancer provide outcome data that allow a statistical estimation of the alpha/beta
      ratio of the linear-quadratic model when combined with clinical data on the
      steepness of the dose-response curve. Results of the large randomized PR5 trial
      by the Ontario Clinical Oncology Group/National Cancer Institute of Canada yield
      an estimate of alpha/beta at 1.12 Gy with 95% confidence interval (-3.3, 5.6) Gy.
      A non-randomized study by Valdagni and colleagues of hyper-fractionation
      delivered BID versus conventional fractionation yields an alpha/beta-estimate of
      8.3 Gy with 95% confidence interval (0.7, 16) Gy. Thus, the confidence interval
      of this latter study cannot exclude even very low values of alpha/beta.
      Furthermore, this point estimate may be an over-estimate if incomplete repair
      plays a role in the BID group of the Italian study. Taken together, the outcomes
      of these two studies still favor a high fractionation sensitivity of prostate
      cancer.

PMID- 15990188
TI  - 3D conformal radiation therapy for prostate cancer in elderly patients.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate if conformal
      radiation therapy for localized prostate cancer with doses of 70 Gy is well
      tolerated in patients aged 75 years or older, and if the side effects and the
      biochemical recurrence free (bNED) survival are comparable to younger patients.
      PATIENTS AND METHODS: Eighty patients>or=75 years received definitive conformal
      radiotherapy for prostate cancer. Acute and late side effects as well as bNED
      survival (ASTRO criteria) were compared to 221 patients younger than 75 years who
      were treated during the same period of time. RESULTS: Median dose to the prostate
      was 70 Gy in both groups. There were no significant differences in acute or late
      side effects between age groups. The frequency of grade III late symptoms was low
      and ranged between 0 and 4% for the evaluated symptoms irrespective of age group.
      Older patients had a better bNED survival than younger patients (bNED survival at
      4 years: 76 vs. 61%, P=0.042). CONCLUSIONS: High-dose conformal radiation therapy
      for prostate cancer is well tolerated in patients aged 75 years or older. In
      terms of bNED survival radiation treatment is at least as effective as it is for
      younger patients.

PMID- 15990190
TI  - Human parvovirus B19 experimental infection in human fibroblasts and endothelial
      cells cultures.
AB  - With the aim to detect what kind of cells, in addition to erythroid progenitors,
      could be involved in the pathogenesis of B19 infection in some connective tissue
      diseases, primary cultures of human fibroblasts (HF) and endothelial cells
      (HUVEC) were exposed to a B19 positive serum (350 genome copies/cell). The
      presence of NS1 and VP1 mRNA, in both HF and HUVEC cultures 1, 2 and 6 days after
      the exposure, indicated infection by B19 virus. However, no significant increase
      of B19 DNA level in the infected HF and HUVEC cultures was detectable through the
      entire incubation period of 6 days. It is possible that HF and HUVEC are not
      permissive for B19 virus replication or, alternatively, that few cells only get
      infected by B19 virus. HF and HUVEC stimulation with different growth factors or
      cytokines could be required for a B19 productive infection to occur.

PMID- 15990191
TI  - Controlled release of retinol from silica particles prepared in O/W/O emulsion:
      the effects of surfactants and polymers.
AB  - Spherical silica particles containing retinol were fabricated by using O/W/O
      multiple emulsion and sol-gel method. In this study, when both hydroxypropyl
      cellulose (HPC) and surfactants such as Tween 20 and Span 80 were used, multiple
      emulsion encapsulating retinol was prepared successfully. The size of water
      droplets and the amount of released retinol depended on the concentration of
      surfactants and PEG polymer. In addition, PEG, PVP, and Pluronic P123 were
      introduced as a stabilizer in the water phase to investigate the effect of
      polymers on the encapsulation efficiency. In the case of PVP, encapsulation
      efficiency of retinol in the silica particles was 7.35% and the lowest. On the
      other hand, in the case of Pluronic P123, it was 30.89% and the highest among
      obtained silica particles. The morphologies of multiple emulsion and silica
      particles were observed by optical microscope (OM) and field emission scanning
      electronic microscope (FE-SEM). In vitro release test and encapsulation
      efficiency were characterized by HPLC.

PMID- 15990192
TI  - Controlling release from the lipidic cubic phase. Amino acids, peptides, proteins
      and nucleic acids.
AB  - Drugs are optimally effective in the therapeutic concentration range. A challenge
      in the delivery area is to design a system that will allow the therapeutic range
      to be accessed and to be maintained for defined periods. The lipidic cubic phases
      have been used as delivery matrices with such properties. For water-soluble
      drugs, release from the cubic phase is controlled by transport through aqueous
      channels that permeate the phase. Channel size can be tuned over wide limits by
      adjusting temperature and lipid identity. Thus, the possibility exists to
      regulate the rate of drug release from the cubic phase. With a view to exploiting
      these features for small molecule, proteinaceous and nucleic acid drugs, we have
      taken a systematic approach toward understanding how cubic phase transport is
      controlled by phase identity and microstructure and by the physical and chemical
      properties of the drug itself. Measurements were made using tryptophan, rubipy,
      DNA and six proteins as drug surrogates and with three hosting lipids.
      Remarkably, transport was observed with apo-ferritin whose size far exceeds that
      of the aqueous channel suggesting a molecular breathing or peristalsis type of
      facilitated release. Exquisite control over release was achieved by adjusting
      electrostatic interaction strength and by His-tag displacement.

PMID- 15990193
TI  - Extracellular superoxide dismutase gene polymorphism is associated with insulin
      resistance and the susceptibility to type 2 diabetes.
AB  - Oxidative stress has been implicated in pancreatic beta-cell damage, insulin
      resistance and vascular function in diabetic patients and the dysfunction of
      antioxidant enzymes may be associated with the pathogenesis of diabetes.
      Extracellular superoxide dismutase (EC-SOD) is found in the extracellular matrix
      of tissues and the major scavenger of superoxide radical. To investigate the role
      of genetic variability for the pathogenesis of type 2 diabetes, we scanned the
      protein coding exon and flanking introns of EC-SOD gene for mutation in Japanese
      type 2 diabetic patients. We identified two missense mutations, Ala40Thr (GCG-
      >ACG) and Arg213Gly (CGG-->GGG), and a silent mutation, Leu53Leu (CTG-->TTG). For
      one of these variants, the Ala40Thr polymorphism, the frequency of Thr allele and
      the number of subjects with Thr allele (Ala/Thr+Thr/Thr) were higher in type 2
      diabetic patients (n=205) than those in non-diabetic subjects (n=220) (33.2%
      versus 24.1%, p=0.003 and 55.6% versus 42.7%, p=0.008, respectively). The
      patients with Thr allele also showed earlier age at diagnosis of diabetes (42.2+/
      7.8 years versus 44.4+/-6.9 years, p=0.037) and higher prevalence of hypertension
      (53.5% versus 38.5%, p=0.032) than those without the allele. Insulin sensitivity,
      furthermore, was evaluated in 71 type 2 diabetic patients with short insulin
      tolerance test (SITT). The patients with Thr allele showed lower insulin
      sensitivity (Kitt value of SITT) than those without the allele (1.78+/-0.78%/min
      versus 2.33+/-1.02%/min, p=0.012), although no significant differences in other
      clinical and biochemical characteristics were observed between two groups. These
      results suggest that the genetic variant of EC-SOD gene is associated with
      insulin resistance and the susceptibility to type 2 diabetes.

PMID- 15990194
TI  - Secular trends in mortality rates for diabetes in Australia, 1907-1998.
AB  - AIMS: To characterise long-term mortality trends for diabetes in Australia during
      the 20th century, and to provide suggestions to health policy-makers. METHODS: A
      descriptive study was conducted using existing dataset. Deaths due to diabetes,
      as underlying cause of death, from 1907 to 1998 were tallied, according to the
      ICD-9. Trends in diabetes mortality (overall population, under-19 and over 40
      year-old age groups) by gender were examined. RESULTS: There was a slightly
      increasing trend in the mortality rate in males over the study period, from
      14.38/100,000 in 1907 to 16.05/100,000 in 1998. Among females, it started from
      19.6/100,000 in 1907, reached the peak in early 1940s and then decreased to
      10.61/100,000 in 1998. There was a reversal sex ratio after late 1960s with
      mortality rates among males were higher than females after 1969. There was a
      significant difference in overall mortality between males and females over study
      period (p<0.001). The mortality trend among the 40 years and over group was
      similar to the overall population. The death rates for the under-19 group
      declined significantly over the study period (p<0.001), but no difference between
      males and females was detected (p>0.05). CONCLUSIONS: The application of insulin
      played an important role in the reduction of diabetes mortality among the under
      19-year-old group. New medical treatment methods to reduce chronic complications
      and other public health interventions could have made a recent contribution to
      reducing death rates. It is also probable that over the study period there has
      been an increase in the likelihood of diabetes being correctly diagnosed.

PMID- 15990195
TI  - A short-term admission improved brachial-ankle pulse wave velocity in type 2
      diabetic patients.
AB  - Brachial-ankle pulse wave velocity (baPWV) is a non-invasive method for assessing
      arterial stiffness associated with atherosclerosis. We examined whether baPWV
      could improve during a 2-week hospital-based education program in patients with
      type 2 diabetes and whether improvement associates with changes in known
      atherogenic risk factors. Body mass index (BMI), blood pressure (BP), fasting
      plasma glucose (FPG), insulin, lipid profiles and baPWV were measured in 32 type
      2 diabetic patients before and after an educational program that included advice
      about nutrition and exercise. Relationship between the changes in baPWV and
      additional parameters, 24h-urinary excretion of C-peptide, visceral and
      subcutaneous fat area by abdominal computer tomography and intima-medial
      thickness (IMT) of the carotid artery by ultrasonography, were also evaluated.
      Baseline values of baPWV significantly correlated with age, duration of diabetes,
      BP, IMT and FPG. BaPWV significantly decreased after the program (-120+/-108.4
      cm/s, P<0.0001) and this change significantly correlated with that of systolic BP
      (r=0.697, P<0.0001) and FPG (r=0.452, P<0.05). These results indicate that short
      term hospitalization with an educational program can improve arterial wall
      stiffness, perhaps due to improvements in BP and glycemic control.

PMID- 15990197
TI  - A census of mammalian imprinting.
AB  - Genomic imprinting, the parent-of-origin-specific silencing of a small proportion
      of genes, introduces a paradoxical vulnerability of hemizygosity into the diploid
      mammalian genome. To facilitate the evaluation of the biological and evolutionary
      significance of imprinting, we have collated a census of known imprinted genes,
      listing 83 transcriptional units of which 29 are imprinted in both humans and
      mice. There is a high level of discordance of imprinting status between the mouse
      and human, even when cases in which the orthologue is absent from one species are
      excluded. A high proportion of imprinted genes are noncoding RNAs or genes
      derived by retrotransposition. Accumulation of functional and comparative data
      for these genes will improve our understanding of imprinting and its contribution
      to mammalian evolution.

PMID- 15990196
TI  - Predicting sustained virological responses in chronic hepatitis C patients
      treated with peginterferon alfa-2a (40 KD)/ribavirin.
AB  - BACKGROUND/AIMS: Prediction of sustained virological response (SVR) during
      treatment would allow clinicians to identify patients most likely to benefit from
      therapy. METHODS: Retrospective analysis of data from 1121 adults with chronic
      hepatitis C treated for 48 weeks with peginterferon alfa-2a (40 KD) 180
      microg/week plus placebo or ribavirin (1000/1200 mg/day), or interferon alfa-2b 3
      MIU three times/week plus ribavirin in a randomized, multinational, study.
      RESULTS: 67% of patients treated with peginterferon alfa-2a (40 KD)/ribavirin
      with early virological responses (HCV RNA negative or > or = 2 log10 decrease) at
      week 12 had SVRs at week 72 (HCV RNA < 50 IU/mL). The negative predictive value
      (NPV) was 97%. The probability of an SVR increased with the rapidity of HCV RNA
      suppression. The highest SVR rates were achieved in patients with rapid
      virological responses at week 4, but the corresponding NPV (74%) is too low for a
      decision criterion. In patients with early virological responses by week 12, the
      SVR rate was approximately 20% lower in those who received <80% compared with
      patients who received > or = 80% of the planned ribavirin dose. CONCLUSIONS:
      Early, sustained suppression of HCV replication portends an SVR. Cessation of
      treatment may be contemplated in patients without a > or = 2 log10 reduction in
      HCV RNA after 12 weeks.

PMID- 15990198
TI  - The regulation of alpha-MSH release by GABA is mediated by a chloride-dependent
      [Ca2+]c increase in frog melanotrope cells.
AB  - In frog melanotrope cells, gamma-aminobutyric acid (GABA) induces a biphasic
      effect, i.e. a transient stimulation followed by a more sustained inhibition of
      alpha-MSH release, and both phases of the GABA effect are mediated by GABAA
      receptors. We have previously shown that the stimulatory phase evoked by GABAA
      receptor agonists can be accounted for by calcium entry. In the present study, we
      have investigated the involvement of the chloride flux on GABA-induced [Ca2+]c
      increase and alpha-MSH release. We show that GABA evokes a concentration
      dependent [Ca2+]c rise through specific activation of the GABAA receptor. The
      GABA-induced [Ca2+]c increase results from opening of voltage-activated L- and N
      type calcium channels, and sodium channels. Variations of the extracellular Cl-
      concentration revealed that GABA-induced [Ca2+]c rise and alpha-MSH release both
      depend on the Cl- flux direction and driving force. These observations suggest
      for the first time that GABA-gated Cl- efflux provokes an increase in [Ca2+]c
      increase that is responsible for hormone secretion.

PMID- 15990199
TI  - Morphine-induced overexpression of prepro-nociceptin/orphanin FQ in cultured
      astrocytes.
AB  - The effects of morphine on the gene expression of prepro-nociceptin/orphanin FQ
      (ppN/OFQ) in various primary cultured brain cells from embryonic day 17, rats
      were studied by use of real-time RT-PCR method. The basal level of ppN/OFQ mRNA
      in terms of ratio to the beta-actin in astrocytes was equivalent to that in
      neurons, but 10-times higher than that in microglia. The addition of 1 microM
      morphine significantly enhanced the ppN/OFQ mRNA levels in cultured astrocytes,
      but not neurons or microglia. The enhancement was observed as early as 1h after
      the addition of morphine, reached maximum at 6h. There was a concentration
      dependency between 30 nM to 1 microM. The morphine-induced enhancement was
      abolished by naloxone, an antagonist of mu opioid peptide receptor (MOP),
      wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, and PD98059, a MEK
      inhibitor, but not by 1,10-phenanthroline, a metalloprotease inhibitor and
      U73122, a phospholipase C inhibitor. These profiles contrast to the data with
      morphine-induced enhancement of brain-derived growth factor (BDNF) gene
      expression in microglia, where 1,10-phenanthroline abolished the expression.
      Furthermore, the ELISA analysis revealed that the immunoreactive ppN/OFQ or N/OFQ
      level was also increased by morphine. The present findings suggest that
      astrocytes could play roles in the neuronal plasticity during morphine chronic
      treatments by enhancing gene expression of anti-opioid peptide, N/OFQ.

PMID- 15990200
TI  - [Spontaneous hypothermia: a series of ten cases, place of Shapiro's syndrome].
AB  - SUBJECT: Hypothermia (defined as a core temperature lower than 35 degrees C) may
      result from accidental causes (exposure to cold, drug intoxications), from
      endocrine disorders (hypothyroidism), or from central or peripheral neurological
      disease. Among the causes of spontaneous hypothermia, the place of spontaneous
      periodic hypothermia or Shapiro's syndrome, of which less than 50 cases in
      children or adults have been reported, remains unclear. METHODS: Case series of
      spontaneous hypothermia in adults, from a register of the French Society of
      Internal Medicine (SNFMI). RESULTS: The ten collected cases of spontaneous
      hypothermia are heterogeneous. In half of the cases, an often ill-labeled
      psychiatric illness and/or epilepsy and/or anti-psychotic medication were found
      contributive. Only 5 cases at best seem to conform to the pattern of spontaneous
      periodic hypothermia or Shapiro's syndrome (in which agenesis of corpus callosum
      is typically found). In such cases, the episodes of hypothermia start with
      profuse hyperhidrosis suggesting a paroxystic reset of the hypothalamic
      thermostat with a lower temperature set point. In none of the cases was found a
      significant encephalic lesion. None of the treatment trials with anti-epileptics
      or cyproheptadine were found useful. Spontaneous hypothermia, whether periodic or
      not, seems to have an unpredictable course, with long periods of remission, and a
      benign long-term outcome. CONCLUSIONS: Spontaneous hypothermia is a symptom of
      likely multifactorial etiology. Even in cases conforming to the definition of
      Shapiro's syndrome, central nervous system anomalies are not unequivocal. No
      specific treatment for spontaneous hypothermia, whether periodic or not, can be
      recommended in the current state of knowledge.

PMID- 15990201
TI  - [Tuberculous sacro-iliitis: a series of twenty-two cases].
AB  - BACKGROUND: Despite their relative rarity, increased awareness of tuberculous
      sacro-iliitis is necessary. Indeed, diagnosis is usually delayed, because of the
      non specific clinical features and the difficulty to explore the sacro-iliac
      joint. OBJECTIVE: To study the characteristics of sacro-iliac joint tuberculosis.
      MATERIALS AND METHODS: A retrospective study of 22 cases of tuberculous sacro
      iliitis collected between 1987 and 2003 in four university hospital centres. All
      our patients were explored clinically and radiologically. Microbiology,
      biochemical and serologic tests were also performed. RESULTS: 13 cases were
      confirmed bacteriologically or histologically and for the remaining nine cases
      evidence of tuberculous sacroiliitis was based on clinical, biological,
      radiological features and outcome on treatment. Inflammatory pain was present in
      almost all cases, and a collected abscess in 11 cases. Standard radiographs were
      also in all cases and ultrasound and CT scan showed an abscess in 8 patients. The
      average duration of treatment was nine months. The outcome was excellent in the
      majority of cases. CONCLUSION: Sacro-iliac joint is difficult to explore and has
      recently beneficiated of technical improvement in imaging and diagnostic. Medical
      treatment of tuberculosis sacro-iliitis is often sufficient.

PMID- 15990202
TI  - Systemic immunization with streptococcal immunoglobulin-binding protein Sib 35
      induces protective immunity against group: a Streptococcus challenge in mice.
AB  - The streptococcal immunoglobulin (Ig)-binding protein Sib 35 binds to IgG, IgM
      and IgA in human, mouse and bovine. Since all group A Streptococcus pyogenes
      (GAS) strains examined express the sib 35 gene, we evaluated the Sib 35 as a
      vaccine candidate against GAS infections. We detected significantly higher anti
      Sib 35 IgG antibody titers in sera from patients with GAS infections than from
      healthy volunteers. Immunization of mice with Sib 35 induced antigen-specific IgG
      antibodies in their sera, and rabbit Sib 35-specific antiserum showed opsonic
      activity. Immunization with Sib 35 enhanced survival rates in mice challenged
      with a GAS strain, while exhibiting no toxicity in hosts. We conclude that Sib 35
      is a promising vaccine for prevention of GAS infections.

PMID- 15990203
TI  - Foliar uptake of cesium from the water column by aquatic macrophytes.
AB  - The probable occurrence and rate of foliar absorption of stable cesium (133Cs)
      from the water column by aquatic macrophyte species was analyzed following the
      addition of 133Cs into a small reservoir near Aiken, South Carolina, USA. An
      uptake parameter u (10(3)Lkg(-1)d(-1)) and a loss rate parameter k (d(-1)) were
      estimated for each species using time series of 133Cs concentrations in the water
      and plant tissues. Foliar uptake, as indicated by rapid increases in plant
      concentrations following the 133Cs addition, occurred in two floating-leaf
      species, Brasenia schreberi and Nymphaea odorata, and two submerged species,
      Myriophyllum spicatum and Utricularia inflata. These species had values of u> or
      =0.75 x 10(3)Lkg(-1)d(-1). Less evidence for foliar uptake was observed in three
      emergent species, including Typha latifolia. Ratios of u to k for B. schreberi,
      M. spicatum, N. odorata and U. inflata can be used to estimate concentration
      ratios (CR) at equilibrium, and these estimates were generally within a factor of
      2 of the CR for 137Cs for these species in the same reservoir. This
      correspondence suggests that foliar uptake of Cs was the principal absorption
      mechanism for these species. Assessments of: (1) the prevalence of foliar uptake
      of potassium, rubidium and Cs isotopes by aquatic macrophytes and (2) the
      possible importance of foliar uptake of Cs in other lentic systems are made from
      a review of foliar uptake studies and estimation of comparable u and k values
      from lake studies involving Cs releases.

PMID- 15990204
TI  - The radiological impact from airborne routine discharges of a modern coal-fired
      power plant.
AB  - In this paper the radiological impact from the airborne routine discharges of a
      modern coal-fired power plant at Langerlo (Belgium) is evaluated. Therefore, the
      natural radioactivity contents of the coal and the fly-ash discharged were
      measured. With a bi-Gaussian plume model the maximum annual values of the 226Ra
      concentration in the air (4.5 nBq/m3) and of the total deposition (1.5 mBq/m2)
      were calculated. The transfer of the radionuclides from air and soil to the
      biospheric media, exposing man, were modelled and the annual, individual,
      effective dose to the critical group, after an assumed life span of the power
      plant of 70 years, was evaluated at 0.05 microSv/y. This is several orders of
      magnitude lower than the annual doses for most power plants reported in the
      literature. The flue gas purification system, extended with a denitrification
      unit and a desulphurisation unit, was found to be the basis for this low impact.

PMID- 15990205
TI  - Upward movement of tritium from contaminated groundwaters: a numerical analysis.
AB  - This paper describes a research-oriented modelling exercise that addresses the
      problem of assessing the movement of tritium from a contaminated perched aquifer
      to the land surface. Participants were provided with information on water table
      depth, soil characteristics, hourly meteorological and evapotranspiration data.
      They were asked to predict the upward migration of tritium through the
      unsaturated soil into the atmosphere. Eight different numerical models were used
      to calculate the movement of tritium. The modelling results agree within a factor
      of two, if very small time and space increments are used. The agreement is not so
      good when the near-surface soil becomes dry. The modelling of the alternate
      upward and downward transport of tritium close to the ground surface generally
      requires rather complex models and detailed input because tritium concentration
      varies sharply over short distances and is very sensitive to many interactive
      factors including rainfall amount, evapotranspiration rate, rooting depth and
      water table position.

PMID- 15990206
TI  - Model testing using data on 137Cs from Chernobyl fallout in the Iput River
      catchment area of Russia.
AB  - Data collected for 10 years following the Chernobyl accident in 1986 have
      provided a unique opportunity to test the reliability of computer models for
      contamination of terrestrial and aquatic environments. The Iput River scenario
      was used by the Dose Reconstruction Working Group of the BIOMASS (Biosphere
      Modelling and Assessment Methods) programme. The test area was one of the most
      highly contaminated areas in Russia following the accident, with an average
      contamination density of 137Cs of 800,000 Bq m-2 and localized contamination up
      to 1,500,000 Bq m-2, and a variety of countermeasures that were implemented in
      the test area had to be considered in the modelling exercise. Difficulties
      encountered during the exercise included averaging of data to account for uneven
      contamination of the test area, simulating the downward migration and changes in
      bioavailability of 137Cs in soil, and modelling the effectiveness of
      countermeasures. The accuracy of model predictions is dependent at least in part
      on the experience and judgment of the participant in interpretation of input
      information, selection of parameter values, and treatment of uncertainties.

PMID- 15990207
TI  - Internal fixation of unstable fracture dislocations of the proximal
      interphalangeal joint.
AB  - We report a group of 14 patients with fracture dislocations of the proximal
      interphalangeal joint with fracture fragments of adequate size to allow reduction
      of the proximal interphalangeal joint and internal mini screw fixation of the
      bone fragment attached to the palmar plate to the base of the middle phalanx.
      Three years after surgery, (range 25-52 months) the average total active range of
      motion of the proximal interphalangeal joint was 100 degrees (range 65-115
      degrees) for the acute group (operation within 14 days of injury, n=7) and 86
      degrees (range 60-110 degrees) for the chronic group (operation on average 46
      days after injury, range 21-120 days, n=7). Longer delay from injury was
      associated with a decreased total range of motion (P=0.028). Further subluxation
      occurred in three chronic group patients, one required further surgery. The key
      to successful treatment of this injury is the re-establishment of joint congruity
      and early mobilization. With appropriate patient selection, pain free,
      satisfactory range of motion can be achieved. There is a risk of persistent
      subluxation or dislocation, particularly if treatment is delayed.

PMID- 15990208
TI  - Copper and trace element fractionation in electrokinetically treated methanogenic
      anaerobic granular sludge.
AB  - The effect of electrokinetic treatment (0.15 mA cm(-2)) on the metal
      fractionation in anaerobic granular sludge artificially contaminated with copper
      (initial copper concentration 1000 mg kg(-1) wet sludge) was studied.
      Acidification of the sludge (final pH 4.2 in the sludge bed) with the intention
      to desorb the copper species bound to the organic/sulfides and residual fractions
      did not result in an increased mobility, despite the fact that a higher quantity
      of copper was measured in the more mobile (i.e. exchangeable/carbonate) fractions
      at final pH 4.2 compared to circum-neutral pH conditions. Also addition of the
      chelating agent EDTA (Cu2+:EDTA4- ratio 1.2:1) did not enhance the mobility of
      copper from the organic/sulfides and residual fractions, despite the fact that it
      induced a reduction of the total copper content of the sludge. The presence of
      sulfide precipitates likely influences the copper mobilisation from these less
      mobile fractions, and thus makes EDTA addition ineffective to solubilise copper
      from the granules.

PMID- 15990209
TI  - Aging and eating in the rural, southern United States: beliefs about salt and its
      effect on health.
AB  - This paper draws upon qualitative research conducted among older adults in the
      rural, southern United States in which they articulated their beliefs and
      experiences with nutrition and foods, and lay models of the connection of diet
      with chronic disease. Salt emerged as a focus of contention. The goals of the
      paper are to (1) present the culturally constructed meaning of salt, (2) contrast
      the cultural meaning with biomedical views, and (3) discuss how these findings
      can be applied to health education and better doctor-patient communication. Data
      were collected in two rural communities characterized by high rates of poverty
      and a high proportion of minority residents. A total of 116 African American,
      Native American and white adults aged 60 years and older participated in 55 in
      depth interviews or seven focus groups. A systematic analysis of text showed that
      salt was a highly contested component of food. While valued for its role in
      traditional foods and cuisine, it also held negative connotations because of
      biomedical links to chronic diseases prevalent in the population. We suggest that
      attempts to control salt intake are made difficult by the changes in taste
      perceptions that accompany aging. Respondents' articulation of salt's role in
      health and disease shows cross-over among different chronic diseases and a lay
      interpretation of blood as the medium through which salt affects disease. These
      older adults' narratives demonstrate their attempts to reconcile the important
      role of traditional foods in their identity as Southerners with their attempts to
      meet medical recommendations for healthy eating.

PMID- 15990210
TI  - Combined effects of uncertainty and organizational justice on employee health:
      testing the uncertainty management model of fairness judgments among Finnish
      public sector employees.
AB  - We examined whether the combination of uncertainty (lack of work-time control,
      and negative changes at work) and organizational justice (i.e., justice of
      decision-making procedures and interpersonal treatment at work) contributes to
      sickness absence. A total of 7083 male and 24,317 female Finnish public sector
      employees completed questionnaires designed to assess organizational justice,
      workload and other factors. Hierarchical regression showed that after adjustment
      for age, income, and health behaviors low procedural and interactional justice
      were related to long sickness absence spells. In accordance with the uncertainty
      management model, these associations were dependent on experienced work-time
      control and perceived changes at work.

PMID- 15990211
TI  - Coping strategies as predictors of psychosocial adaptation in a sample of elderly
      veterans with acquired lower limb amputations.
AB  - This study examines the contribution of demographic/amputation-related variables
      and coping strategies to the prediction of psychosocial adaptation in veterans
      with acquired lower limb amputations. Multiple indicators of the psychosocial
      adjustment of 796 individuals in the UK aged between 26-92 years with lower limb
      amputations were assessed. Hierarchical linear regressions were performed to
      investigate relationships between demographic/amputation-related variables (i.e.
      age, time since amputation, amputation level and amputation aetiology), the
      dimensions of coping (namely problem solving, seeking social support and
      avoidance) and self-reported adaptation to amputation, as well as symptoms of
      intrusion, anxiety and depression. Results indicated that coping styles were
      important predictors of psychosocial adaptation. Avoidance was strongly
      associated with psychological distress and poor adjustment. In contrast, problem
      solving was negatively associated with depressive and anxious symptomatology
      whereas seeking social support was negatively associated with symptoms of
      depression and positively associated with social adaptation. These findings
      suggest the potential for interventions designed to promote particular coping
      strategies to improve psychosocial outcomes.

PMID- 15990212
TI  - Cross-district utilization of general hospital care in Nova Scotia: policy and
      service delivery implications for rural districts.
AB  - Acute care regionalization has been pursued in health systems throughout the
      industrial world as a means of achieving better patient outcomes for specialized
      services. The evidence in support of this policy direction is compelling, but is
      primarily based on highly specialized care, such as coronary and cancer
      treatments. There exists another, largely unintended, form of regionalization
      that involves the flow of patients from smaller urban and rural settings to major
      urban centres to obtain routine procedures. Using data from the Nova Scotia
      Discharge Abstract Database, this paper presents an analysis of cross-district
      utilization of secondary level acute care. In particular, we examine spatial,
      demographic and individual healthcare seeking characteristics of those residents
      who obtained relatively routine hospital care in a different district in
      2000/2001, even though an equivalent level of service was available within their
      home district. Implications of cross-district utilization for the viability of
      medical service provision in smaller centres in the province and elsewhere are
      discussed.

PMID- 15990213
TI  - Perceived change in quality of life during the menopause.
AB  - The directly attributable effect of menopausal transition on women's quality of
      life (QoL) remains unclear. This study investigates the relationship between
      perceived change in QoL and menopausal transition status, socio-economic
      circumstances, lifestyle factors, and life stress. Prospective data were
      collected from a cohort of 1525 British women followed up since their birth in
      1946 and annually from 47 to 54 years. Following factor analysis, the 10 survey
      items for perceived change were combined into three QoL domains: physical health
      (physical health, energy level, and body weight), psychosomatic status (nervous
      and emotional state, self-confidence, work life, ability to make decisions, and
      ability to concentrate), and personal life (family life and time for self,
      hobbies, and interests). In the fully adjusted model, the most important risk
      factor for decline in all three domains was work or family related stress
      (p<0.001). Menopausal transition status was significantly associated with change
      in physical health (p<0.001) and psychosomatic (p<0.001) domains, but not
      personal life. Women who were perimenopausal for at least a year perceived
      decline in physical (p=0.009) and psychosomatic (p=0.05) domains compared with
      premenopausal women, while those on hormone replacement therapy (HRT) for at
      least a year reported relative improvement (physical p=0.02, psychosomatic
      p=0.06). Apart from work and family-related stress, physical inactivity was
      associated with a relative decline (p=0.03) in the physical health domain, and
      nulliparity with a relative decline in the personal life domain (p=0.006). Both
      psychosomatic and personal life domains declined significantly with age (p<0.0001
      and p=0.003, respectively). Women with four or more children reported a relative
      improvement in the psychosomatic (p=0.05) domain. In terms of the three QoL
      domains, women's experience of the menopausal transition appears complex,
      potentially involving a range of other factors and influences in their lives, and
      is by no means overwhelmingly negative.

PMID- 15990214
TI  - Dermatotoxicity of epicutaneously applied anticoagulant warfarin.
AB  - Dermatotoxic effects of epicutaneous application of a first-generation
      anticoagulant, warfarin (WF) were examined in rats. Selected parameters of skin
      activity were determined 24h following warfarin application, including metabolic
      viability of skin explants, some aspects of oxidative activity in skin tissue
      homogenates and inflammatory/immune relevant activity of epidermal cells from
      warfarin-treated skin. No changes in skin metabolic viability (MTT reduction)
      were noted ex vivo following WF application, suggesting the absence of immediate
      toxicity for skin. In contrast, increased formation of malondialdehyde (MDA),
      with a decrease in protein and non-protein thiols in homogenates of warfarin
      treated skin was demonstrated, pointing to prooxidant activity in warfarin
      treated skin. Increased costimulatory activity of epidermal cells isolated from
      warfarin-exposed skin in Con-A-stimulated T-cell activation/proliferation assay
      was noted, reflecting proinflammatory and immune-modulating capacity of warfarin
      for epidermis. No evident differences in skin histology between control and
      warfarin-treated skin were found at that time point, while striking changes in
      tissue integrity, cellularity and appearance 72 h following WF application were
      noted. The observed histological picture probably reflects a
      regenerative/inflammatory program related to oxidant/inflammation-type warfarin
      evoked injury to the skin. Presented data demonstrate the potential of
      epicutaneously applied warfarin to modulate local skin activity in rats.

PMID- 15990215
TI  - Comparison of effects of different hand positions during cardiopulmonary
      resuscitation.
AB  - AIM: The technique of chest compression recommended in the recent international
      guidelines is different from that which was traditionally used in Hungary. While
      compression force, location, frequency and duty cycle are all identical, the
      position of the hand on the chest is different. The aim of our study was to
      compare these two methods concerning the area and location of the surface
      compressed on the chest wall. METHODS: Thirty-eight doctors were trained in both
      compression methods. Compressions were carried out on an AMBU Man-C manikin. The
      compressed surface, marked by using a carbon paper, was projected on to a
      standardised 10 mm x 10 mm matrix to measure the area and location. The chest
      surface was marked subsequently as green, yellow and red areas to identify the
      correct position, incorrect position and dangerous areas. All subjects did chest
      compressions using both techniques (I, International; H, traditional Hungarian)
      in a random order each for 30 s. RESULTS: The surface area compressed was
      significantly larger by the H method than the I method (73.46 (+/-17.11) versus
      41.75 (+/-11.08), p<0.005). 8.07 (+/-1.91) cm2 of an area considered dangerous
      were compressed by the H method compared to 2.93 (+/-0.78) cm2 by the I method
      (p<0.005). CONCLUSION: Comparing the two different methods of chest compressions,
      the hand position recommended by the recent international guidelines seems to be
      more safe as it compresses a smaller area which might cause injury.

PMID- 15990216
TI  - Resuscitation great. Larrey and Percy--a tale of two barons.

PMID- 15990217
TI  - River pollution from non-point sources: a new simplified method of assessment.
AB  - Assessment of the pollution of water bodies from non-point sources is a complex
      data- and time-consuming task. The potential non-point pollution index (PNPI), is
      a new tool designed to assess the global pressure exerted on rivers and other
      surface water bodies by different land uses. The main feature of PNPI is the wide
      availability of its input data. Very detailed input maps, often lacking over many
      areas, are not needed for PNPI calculation. As a consequence of the input data
      used, the modelling of physical reality and of processes is heavily simplified.
      The authors counterbalanced such a simplification using an 'expert system'
      approach. The system bypasses the accurate representation of the physical reality
      to assess globally the pollution potential of different land uses according to
      the judgement of scientists. The scientific community proposes many models for
      depicting the dynamics of pollutants coming from diffuse sources. Most of them
      can be grouped into two broad categories: statistical models and physically based
      models. PNPI belongs to neither of the above-mentioned groups. PNPI is a GIS
      based, watershed-scale tool designed to inform decision makers and public opinion
      about the potential environmental impacts of different land management scenarios.
      PNPI applies the multicriteria technique to pollutant dynamics and water quality.
      The pressure exerted on water bodies by diffuse pollution coming from land units
      is expressed as a function of three indicators: land use, run-off and distance
      from the river network. They are calculated from land use data, geological maps
      and a digital elevation model (DEM). The weights given to different land uses and
      to the three indicators were set according to experts' evaluations and allow
      calculation of the value of the PNPI for each node of a grid representing the
      watershed; the higher the PNPI of the cell, the greater the potential impact on
      the river network. The output of the calculation is presented in the form of maps
      that highlight areas that are more likely to produce pollution. Last,
      possibilities, strategies and results of the validation of the PNPI are
      described. In the authors' view, the explicit link between land use and potential
      pollution on which PNPI is based, together with its high communication potential,
      make it particularly interesting for a participatory and integrated approach to
      land management and environmental protection.

PMID- 15990218
TI  - Stakeholder preferences towards conservation versus development for a wetland in
      Sri Lanka.
AB  - In determining the importance of criteria in the management of wetlands, two key
      issues arise: that is whether they should be conserved for environmental
      benefits, or whether they should be used for development activities. This is
      indeed the conflict faced in many natural resource management problems. This
      paper considers the development of stakeholder preferences in a region in Sri
      Lanka for representative criteria based on defined objectives for wetland
      management. Data were obtained spatially from a paired comparison based survey
      using the analytic hierarchy process to investigate the importance attached to
      the criteria by stakeholders who live and work in the wetland region. Distinct
      groups showing different concerns towards importance of objectives are shown to
      exist over the whole area and spatially. However, the consensus view of favouring
      conservation of the environment is indicated by 80% of the sample.

PMID- 15990219
TI  - Treatment of overactive bladder in the older patient: pooled analysis of three
      phase III studies of darifenacin, an M3 selective receptor antagonist.
AB  - AIM: To evaluate the efficacy, tolerability and safety of darifenacin, an M(3)
      selective receptor antagonist, in the subgroup of older patients from a pooled
      analysis of three phase III, multicentre, randomized, double-blind clinical
      trials in patients with overactive bladder (OAB). PATIENTS AND METHODS: 317
      patients aged > or =65 years with OAB symptoms (urge incontinence, urgency and
      frequency) received up to 12 weeks' oral treatment with darifenacin 7.5 mg or 15
      mg once daily or matching placebo. Efficacy was evaluated from daily electronic
      diary records. Safety endpoints included withdrawal rates and treatment-related
      adverse events. RESULTS: Darifenacin treatment of patients aged > or =65 years
      was associated with a dose-related, significant improvement of all the major
      symptoms of OAB. At week 12, the median reduction in incontinence episodes/week
      was greater with darifenacin 7.5 mg or 15 mg than in the corresponding placebo
      arms (66.7% vs. 34.8% and 75.9% vs. 44.8%, respectively, both p < 0.001). Both
      doses were also significantly superior to placebo in improving micturition
      frequency (both p < 0.001), bladder capacity (volume voided) (darifenacin 7.5 mg,
      p = 0.018, darifenacin 15 mg, p < 0.001), and the frequency of urgency episodes
      (both p < 0.001). Darifenacin was well tolerated. The most common treatment
      related adverse events were dry mouth (7.5 mg, 20.6%; 15 mg, 30.9%; placebo,
      4.5%) and constipation (7.5 mg, 18.6%; 15 mg, 23.6%; placebo, 6.4%), typically
      mild or moderate. Use of constipation remedies (laxatives, stool softeners or
      fibre supplements) was low and similar between groups (7.5 mg, 10.3%; 15 mg,
      16.4%; placebo, 10.0%). There were few withdrawals due to treatment-related
      adverse events (7.5 mg, 1.0%; 15 mg, 9.1%; placebo, 2.7%), and no nervous system
      or cardiovascular safety concerns. CONCLUSIONS: The results demonstrate excellent
      efficacy, tolerability and safety with darifenacin 7.5 mg and 15 mg once-daily
      treatment for OAB in older patients.

PMID- 15990220
TI  - A comparison of the efficacy and tolerability of solifenacin succinate and
      extended release tolterodine at treating overactive bladder syndrome: results of
      the STAR trial.
AB  - OBJECTIVE: To compare two new generation antimuscarinics at their recommended
      doses for treatment of overactive bladder syndrome (OAB). METHODS: A prospective,
      double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted
      to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine
      extended release (ER) 4 mg once daily in OAB patients. After 4 weeks of treatment
      patients had the option to request a dose increase but were dummied throughout as
      approved product labelling only allowed an increase for those on solifenacin.
      RESULTS: Solifenacin, with a flexible dosing regimen, showed greater efficacy to
      tolterodine in decreasing urgency episodes, incontinence, urge incontinence and
      pad usage and increasing the volume voided per micturition. More solifenacin
      treated patients became continent and reported improvements in perception of
      bladder condition assessments. The majority of side effects were mild to moderate
      in nature, and discontinuations were comparable and low in both groups.
      CONCLUSIONS: Solifenacin, with a flexible dosing regimen, was found to be
      superior to tolterodine ER with respect to the majority of the efficacy
      variables.

PMID- 15990221
TI  - Tumor size, vascular density and proliferation as prognostic markers in GS 6 and
      GS 7 prostate tumors in patients with long follow-up and non-curative treatment.
AB  - OBJECTIVES: To investigate the prognostic value of potential markers in
      localized, Gleason score 6 and 7 prostate cancer (PC). METHODS: From a
      consecutive series of men with PC diagnosed at transurethral resection (1975
      1990), specimens from 132 patients without metastases, with Gleason score (GS) 6
      (n=80) or 7 (n=52) tumors followed with watchful waiting were examined. The
      fraction of resected prostate tissue containing cancer, the micro-vessel density
      (v.d.) when stained for endoglin or von Willebrand factor (vWf), and the
      percentage of Ki-67 labeled tumor cells were measured using immunohistochemistry.
      RESULTS: High levels of vWf v.d., endoglin v.d., and percent cancer of the TURP
      specimen were significantly associated with short cancer-specific survival in
      Kaplan-Meier analysis of all patients with GS 6 and 7 tumors. Interestingly, a
      combined estimate of percent cancer and vWF v.d. could be used to identify a
      large subset (50%) of GS 6 tumors with only a 2.5% risk of PC death within 15
      years. None of the tested markers gave independent prognostic information for the
      GS 7 tumors. CONCLUSIONS: Estimates of tumor size and vascular density may
      identify a large proportion of non-aggressive GS 6, but not GS 7, tumors.

PMID- 15990222
TI  - Induction of p53 and drug resistance following treatment with cisplatin or
      paclitaxel in ovarian cancer cell lines.
AB  - Treatment failures result from resistance to chemotherapy in ovarian cancer. The
      effect of cisplatin and paclitaxel treatments on chemosensitivity was studied in
      ovarian cancer cells developed from a patient with stage IIIC disease. Cells (UL
      3A, UL-3B) that recovered from cisplatin (Cis) and paclitaxel (Tax) treatments
      showed higher levels of p53, mdr-1 and chemoresistance than untreated controls.
      EC50 values of Cis and Tax for UL-3A clones were 7.2-34.6, average 20.9
      microg/ml, while UL-3B clones ranged from 11.8-252.0 microg/ml, with a mean value
      of 73.2 microg/ml for Cis, and 260.0-4400.0 nM (mean 2555.0 nM) for Tax.
      Selection pressures during treatment may contribute to drug resistance.

PMID- 15990223
TI  - Localization of the ABCG2 mitoxantrone resistance-associated protein in normal
      tissues.
AB  - Reduced drug accumulation due to overexpression of individual members of the ATP
      binding cassette (ABC) superfamily of membrane transporters has been investigated
      as a cause of multidrug resistance and treatment failure in oncology. This study
      was designed to develop an immunohistochemical assay to determine the expression
      and localization of the 72kDa ABC half-transporter ABCG2 in normal tissues.
      Formalin-fixed, paraffin embedded archival tissue from 31 distinct normal tissues
      with an average of eight separate tissue samples of each were immunostained with
      rabbit-anti-ABCG2 antibody 405 using a modified avidin-biotin procedure. As a
      negative control, each sample was also stained with antibody pre-adsorbed with
      peptide to assess background staining. As a means of verification, selected
      tissues were also stained with the commercially available monoclonal antibody
      5D3. ABCG2 positivity was consistently found in alveolar pneumocytes, sebaceous
      glands, transitional epithelium of bladder, interstitial cells of testes,
      prostate epithelium, endocervical cells of uterus, squamous epithelium of cervix,
      small and large intestinal mucosa/epithelial cells, islet and acinar cells of
      pancreas, zona reticularis layer of adrenal gland, kidney cortical tubules and
      hepatocytes. Placental syncytiotrophoblasts showed both cytoplasmic and surface
      staining. Our results support a hypothesis concluding that ABCG2 plays a role in
      the protection of organs from cytotoxins. However, many of the cell types
      expressing ABCG2 have a significant secretory function. These data suggest a dual
      function for ABCG2 in some tissues: the excretion of toxins and xenobiotics
      including anti-cancer agents and a potential, as-yet undefined role in the
      secretion of endogenous substrates.

PMID- 15990224
TI  - Hepatitis B virus X protein induces apoptosis in hepatoma cells through
      inhibiting Bcl-xL expression.
AB  - The X protein of hepatitis B virus (HBx) exhibits numerous activities affecting
      gene transcription, intracellular signal transduction, cell proliferation and
      apoptosis. Recent studies showed that HBx induced apoptosis by causing loss of
      mitochondrial membrane potential, suggesting that HBx-mediated apoptosis is
      mitochondria-dependent. However, the molecular mechanism of the gene in this
      pathway is still far from understood. In this study, we demonstrated that
      introduction of HBx into a hepatocellular carcinoma cell line, Hep3B, caused
      apoptosis and sensitized the cell to TNFalpha-induced cell killing. Over
      expression of Bcl-xL, an anti-apoptotic Bcl-2 family protein, prevented cell
      death dragged by HBx. Importantly, expression of HBx in Hep3B cells reduced Bcl
      xL mRNA and protein levels, but did not regulate other Bcl-2 family members.
      Although, HBx itself did not affect intracellular distribution of cytochrome c,
      an enhanced release of cytochrome c from mitochondria was observed when TNFalpha
      was applied. Thus, the introduction of HBx into Hep3B cells induces apoptosis and
      sensitizes Hep3B cells to TNFalpha-mediated cell killing, and these processes may
      accomplish through inhibiting Bcl-xL expression and subsequently promoting
      cytochrome c release from mitochondria.

PMID- 15990225
TI  - Adsorption of phenol from aqueous solution by using carbonised beet pulp.
AB  - The beet pulp, a major low value by-product in sugar industry was used to prepare
      carbon for phenol adsorption. It was produced by carbonisation in N2 atmosphere
      at 600 degrees C for 1.5 h. The surface area of beet pulp carbon was measured as
      47.5 m2g(-1) by using BET method. The adsorption studies of phenol from aqueous
      solution on beet pulp carbon (BPC) have been studied in the range of 25-500 mgdm(
      3) initial phenol concentrations and at the temperatures of 25, 40 and 60 degrees
      C. The maximum phenol adsorption capacity was obtained as 89.5 mgg(-1)at the
      temperature of 60 degrees C at pH=6.0. The Freundlich and Langmuir adsorption
      models were used for the mathematical description of the adsorption equilibrium
      and it was reported that experimental data fitted very well to Freundlich model,
      although they could be modelled by the Langmuir equation. Batch adsorption
      models, based on the assumption of the pseudo-first order and pseudo-second order
      mechanism, were applied to examine the kinetics of the adsorption. The results
      showed that kinetic data were followed more closely the pseudo-second order model
      than the pseudo-first order. The thermodynamic parameters such as, equilibrium
      constant (K), Gibbs free energy changes (DeltaG degrees ), standard enthalpy
      change (DeltaH degrees ) and standard entropy change (DeltaS degrees ) had been
      determined. The results show that adsorption of phenol on BPC is an endothermic
      and spontaneous in nature.

PMID- 15990226
TI  - A risk-based approach to land-use planning.
AB  - The Seveso II-Directive requires that the objectives of preventing major
      accidents and limiting their consequences be taken into account by the Member
      States in their land-use policies and/or other relevant policies. This is to be
      achieved by ensuring adequate distances between industrial establishments and
      residential areas, areas of public use and areas of particular natural
      sensitivity or interest. A risk-based framework implemented in a computer program
      is presented which enables one to calculate adequate distances. The criterion
      used is a limit on the individual risk of death. The method is a simplified risk
      analysis which represents the plant, whose characteristics are normally unknown
      at the stage of land-use planning, by generic frequencies of release for process
      units and storage tanks. Their number depends on the size of the site to be
      allotted. The procedure is capable of addressing the siting of new establishments
      and, with due regard to the simplifications used, modifications to and new
      developments in the vicinity of existing establishments. Given the numerous
      assumptions, which have to be made, the framework represents a convention.

PMID- 15990227
TI  - Approximation of flammability region for natural gas-air-diluent mixture.
AB  - The growing implementation of exhaust gas recirculation (EGR) in reducing NO(x)
      emissions of engine is of paramount motivation to perform a fundamental research
      on the flammability characteristics of fuel-air-diluent mixtures. In this work,
      the influences of EGR on the flammability region of natural gas-air-diluent
      flames were experimentally studied in a constant volume bomb. An assumption of
      critical burning velocity at flammability limit is proposed to approximately
      determine the flammability region of these mixtures. Based on this assumption, an
      estimation of the flammability map for natural gas-air-diluent mixtures was
      obtained by using the empirical formula of burning velocity data. The
      flammability regions of natural gas-air mixtures with EGR are plotted versus the
      EGR rate. From the comparison of estimated results and experimental measurements,
      it is suggested that the accuracy of prediction is largely dependent upon the
      formula of burning velocity used. Meanwhile, the influence of pressure on the
      critical burning velocity at flammability limit is also investigated. On the
      basis of the pressure dependence criterion, the estimation was performed for the
      circumstance of high temperature and pressure, and the prediction results still
      agree well with those of experiments.

PMID- 15990228
TI  - Determination of the equilibrium, kinetic and thermodynamic parameters of
      adsorption of copper(II) ions onto seeds of Capsicum annuum.
AB  - Adsorption of copper ions onto Capsicum annuum (red pepper) seeds was
      investigated with the variation in the parameters of pH, contact time, adsorbent
      and copper(II) concentrations and temperature. The nature of the possible
      adsorbent and metal ion interactions was examined by the FTIR technique. The
      copper(II) adsorption equilibrium was attained within 60 min. Adsorption of
      copper(II) ions onto C. annuum seeds followed by the Langmuir, Freundlich and
      Dubinin-Radushkevich (D-R) isotherm models. Maximum adsorption capacity (q(max))
      of copper(II) ions onto red pepper seeds was 4.47x10(-4) molg(-1) at 50 degrees
      C. Three kinetic models including the pseudo-first-order, pseudo-second-order and
      intraparticle diffusion equations were selected to follow the adsorption process.
      Kinetic parameters such as rate constants, equilibrium adsorption capacities and
      related correlation coefficients, for each kinetic model were calculated and
      discussed. It was indicated that the adsorption of copper(II) ions onto C. annuum
      seeds could be described by the pseudo-second-order kinetic model and also
      followed the intraparticle diffusion model up to 60 min, but diffusion is not
      only the rate controlling step. Thermodynamics parameters such as the change of
      free energy, enthalpy and entropy were also evaluated for the adsorption of
      copper(II) ions onto C. annuum seeds.

PMID- 15990229
TI  - Arsenic removal via electrocoagulation from heavy metal contaminated groundwater
      in La Comarca Lagunera Mexico.
AB  - Arsenic contamination is an enormous worldwide problem. A large number of people
      dwelling in Comarca Lagunera, situated in the central part of northern Mexico,
      use well water with arsenic in excess of the water standard regulated by the
      Secretary of Environment and Natural Resources of Mexico (SEMARNAT), to be
      suitable for human health. Individuals with lifetime exposure to arsenic develop
      the classic symptoms of arsenic poisoning. Among several options available for
      removal of arsenic from well water, electrocoagulation (EC) is a very promising
      electrochemical treatment technique that does not require the addition of
      chemicals or regeneration. First, this study will provide an introduction to the
      fundamental concepts of the EC method. In this study, powder X-ray diffraction,
      scanning electron microscopy, transmission Mossbauer spectroscopy and Fourier
      transform infrared spectroscopy were used to characterize the solid products
      formed at iron electrodes during the EC process. The results suggest that
      magnetite particles and amorphous iron oxyhydroxides present in the EC products
      remove arsenic(III) and arsenic(V) with an efficiency of more than 99% from
      groundwater in a field pilot scale study.

PMID- 15990230
TI  - Wet STEM: a new development in environmental SEM for imaging nano-objects
      included in a liquid phase.
AB  - Environmental scanning electron microscopy (ESEM) enables wet samples to be
      observed without potentially damaging sample preparation through the use of
      partial water vapour pressure in the microscope specimen chamber. However, in the
      case of latices in colloidal state or microorganisms, samples are not only wet,
      but made of objects totally submerged in a liquid phase. In this case, under
      classical ESEM imaging conditions only the top surface of the liquid is imaged,
      with poor contrast, and possible drifting of objects. The present paper describes
      experiments using a powerful new Scanning Transmission Electron Microscopy (STEM)
      imaging system, that allows transmission observations of wet samples in an ESEM.
      A special device, designed to observe all sorts of objects submerged in a liquid
      under annular dark-field imaging conditions, is described. Specific features of
      the device enable to avoid drifting of floating objects which occurs in the case
      of a large amount of water, thus allowing slow-scan high-definition imaging of
      particles with a diameter down to few tens of nm. The large potential
      applications of this new technique are then illustrated, including the imaging of
      different nano-objects in water. The particular case of grafted latex particles
      is discussed, showing that it is possible to observe details on their surface
      when submerged in water. All the examples demonstrate that images acquired in wet
      STEM mode show particularly good resolution and contrast, without adding
      enhancing contrast objects, and without staining.

PMID- 15990231
TI  - Re-evaluation of patients involved in a trichinellosis outbreak caused by
      Trichinella britovi 15 years after infection.
AB  - This study re-evaluates 13 out of 48 subjects involved in a trichinellosis
      outbreak that occurred in Central Italy (Umbria Region) in 1988 resulting from
      the consumption of raw boar meat harboring Trichinella britovi. During the
      outbreak, 28 of 48 serologically positive subjects were asymptomatic, whereas 20
      subjects presented one or more clinical signs including but not limited to fever,
      myalgia, periorbital oedema and conjunctivitis. Several patients were
      hospitalized with severe clinical signs requiring treatment with mebendazole and
      corticosteroids. Upon re-evaluation of 13 patients, none presented clinical
      signs; however, three still had increased CPK or LDH serum levels with some signs
      of electromyographic changes. In this study, enzyme immunoassays (EIA) were used
      to test the 13 positive sera for reactivity with T. britovi antigens using both
      excretory/secretory (E/S) antigens and a synthetic antigen composed of beta
      tyvelose conjugated to bovine serum albumin. Western blots (WB) were also carried
      out using a commercial kit. Studies using EIA with E/S antigen identified five
      positive sera; however, using beta-tyvelose as antigen, only one positive sample
      was identified. Nearly all sera reacted positively with one or more Trichinella
      antigens when analyzed by WB, in particular to the 45 k Da beta-tyvelose
      containing glycoprotein. Results indicate that T. britovi, though less pathogenic
      than other Trichinella species, is clearly capable of inducing sustainable
      sequelae.

PMID- 15990232
TI  - Proceedings of the 11th International Conference on Trichinellosis. August 8-12,
      2004. San Diego, California, USA.

PMID- 15990233
TI  - Influence of adjuvant formulation on the induced protection of mice immunized
      with total soluble antigen of Trichinella spiralis.
AB  - Vaccination of pigs against the helminth nematode Trichinella could be a good
      alternative to prevent the risk of human infection. In order to develop an
      efficient and safe vaccine, the choice of the adjuvant is an important issue. In
      this study, two adjuvants were selected to prepare vaccines based on total
      soluble Trichinella spiralis muscle larvae (ML) antigen: Montanide ISA 70 water
      in oil emulsion and Montanide IMS nanoparticles. Aluminium hydroxide was used as
      a reference adjuvant. The immune response was checked by ELISA of parasite
      antigen specific IgG1 and IgE. Finally, protection induced in vaccinated mice was
      measured after a T. spiralis challenge by counting ML burdens. The results
      clearly showed an impact of adjuvants on the specific IgG1 and IgE antibody
      responses against T. spiralis. Differences were observed between the rates of
      protection induced according to the type of formulation, although the three
      adjuvants tested were able to enhance the humoral immune response. This work
      demonstrated the need to use an adjuvant to obtain a specific IgG1 and IgE
      responses directed against the total soluble extract of T. spiralis.

PMID- 15990234
TI  - Trichinella pseudospiralis from a wild pig in Texas.
AB  - In December 2001, the routine inspection of a wild boar intended for human
      consumption revealed the presence of Trichinella ssp. larvae. Biological,
      morphological and genetic analyses demonstrated the parasite to be Trichinella
      pseudospiralis. This is the second report of T. pseudospiralis in the United
      States and the first report of the parasite in a food animal species in the U.S.

PMID- 15990235
TI  - Genetic algorithm for large-scale maximum parsimony phylogenetic analysis of
      proteins.
AB  - Inferring phylogeny is a difficult computational problem. For example, for only
      13 taxa, there are more then 13 billion possible unrooted phylogenetic trees.
      Heuristics are necessary to minimize the time spent evaluating non-optimal trees.
      We describe here an approach for heuristic searching, using a genetic algorithm,
      that can reduce the time required for weighted maximum parsimony phylogenetic
      inference, especially for data sets involving a large number of taxa. It is the
      first implementation of a weighted maximum parsimony criterion using amino acid
      sequences. To validate the weighted criterion, we used an artificial data set and
      compared it to a number of other phylogenetic methods. Genetic algorithms mimic
      the natural selection's ability to solve complex problems. We have identified
      several parameters affecting the genetic algorithm. Methods were developed to
      validate these parameters, ensuring optimal performance. This approach allows the
      construction of phylogenetic trees with over 200 taxa in practical time on a
      regular PC.

PMID- 15990236
TI  - Reconstruction of total and near-total nostril stenosis in the burned nose with
      gingivo-mucosal flap.

PMID- 15990237
TI  - Pediatric hand injury induced by treadmill.
AB  - Korea has recently seen an increase in pediatric hand injuries associated with
      treadmills. This study was conducted to identify the frequency, patterns,
      treatment and outcome of these injuries, in the hope of developing preventive
      programs. A retrospective review of the medical records of 25 children, all with
      treadmill-induced friction hand injuries, was conducted at the Hallym Burn
      Centre, Hangang Sacred Heart Hospital, Seoul, Korea, during the period of January
      2002 to March 2004. The injuries constituted 1.4% of the total number of
      pediatric burn injury admissions. Male toddlers were affected more than female.
      The mean age of the children was 3.9+/-3.2 (3, 1-15) years old. Most injuries
      occurred in spring. Treadmill friction inflicted deep second or third degree
      burns, small in area (1.6+/-1.0% of TBSA). All lesions involved the hands and
      forearms, with 60% on the right. Most patients (64%) underwent surgical
      management 13+/-5 days after the injury. The volar surface of the hand was more
      affected than the dorsal side (27 versus 8). Treatment was mainly with full
      thickness skin graft (60%) and long-term surgical outcomes were excellent. Such
      injuries may be prevented by educating the public about the potential risks of
      the treadmill, and by the development of additional safety designs. Changes in
      management protocols and treatment policies would improve the provision of
      appropriate care.

PMID- 15990238
TI  - Current status of burn care facilities: a nationwide survey.
AB  - The problems associated with burn injuries are wide-ranging, and the social and
      economic impacts of burns affect all of society. Only burn units have the
      capability to properly care for these patients, and this specialization
      translates to increased costs. The aim of this study was to examine the current
      status of burn units in Turkey. There are no reliable epidemiological data on
      burns and burn units in our country, so we conducted our own survey. In March
      2003, Turkey had 1198 hospitals with 159,290 patient beds. To collect data
      related to burn care centers, we mailed a questionnaire to every hospital (974
      total sent) and a different questionnaire to every City Health Directorate (81
      total sent). Seven hundred and seventy-seven hospitals (79.8%) responded, and the
      results indicate that the number of burn care centers has risen significantly in
      the past decade. At most centers, plastic-reconstructive surgeons and general
      surgeons are the physicians who care for burn patients. The survey findings
      indicate that Turkey needs many more burn centers, and also better quality units.
      In addition, in-service training of health care professionals is required. As
      well, a curriculum should be developed for continuous public education geared
      towards burn prevention and first aid.

PMID- 15990239
TI  - Static thermography revisited--an adjunct method for determining the depth of the
      burn injury.
AB  - The aim of the study was to investigate the relationship between the static
      thermography figure of merit DeltaT (the difference in mean values of skin area
      temperature for the burn wound area and the unaffected reference skin area) and a
      means of burn classification which would be most suitable for the choice of
      treatment. The work was an in vivo animal experiment. Statistical analysis showed
      a high correlation between the DeltaT parameter and histopathological assessment.
      With regard to the choice of treatment, the most useful correlation was found to
      be that between DeltaT and the classification of burn wounds into those healed in
      3 weeks and those unhealed. The results of this study have revealed a
      quantitative criterion DeltaT for burn classification. The study suggests that
      particular burn centres using static thermography use a DeltaT parameter based on
      their own values for burn classification so as to group burn wounds into those
      that healed in 3 weeks and those that did not heal. This criterion should be
      independent of and replace other classification systems. A criterion for the
      proper choice of burn treatment would then be made more readily available.

PMID- 15990240
TI  - Direct evidence for mutual interactions between perineuronal astrocytes and
      interneurons in the CA1 region of the rat hippocampus.
AB  - Recent studies have demonstrated that astrocytes express a variety of ion
      channels and neurotransmitter receptors and can modulate the activity of neurons.
      Since a single astrocyte makes tight contacts with many neighboring neuronal
      cells, they can provide efficient and wide modulation of neuronal networks. Here,
      we provide direct evidence for mutual interactions between perineuronal
      astrocytes and interneurons in the stratum radiatum of the rat hippocampus.
      Direct depolarization of a perineuronal astrocyte suppressed the excitatory
      postsynaptic currents in an adjacent interneuron and increased the paired-pulse
      ratio, indicating that perineuronal astrocytes have a suppressive effect on
      presynaptic elements. Moreover, perineuronal astrocyte activation modulated the
      directly induced firing pattern of the interneuron, with initial facilitation and
      subsequent suppression. Conversely, direct firing of the interneuron depolarized
      the membrane potential and reduced the input resistance of the perineuronal
      astrocyte. These results directly demonstrate the existence of bidirectional
      interactions between neurons and perineuronal astrocytes.

PMID- 15990241
TI  - Sweet intake, sweet-liking, urges to eat, and weight change: relationship to
      alcohol dependence and abstinence.
AB  - INTRODUCTION: Linkages between alcohol dependence (AD) and abstinence and aspects
      of food ingestion and preference have been described in animals and humans,
      including (1) eating sweets decreases urges to drink alcohol; (2) preferences for
      highly sweet tastants is associated with alcohol dependence; and (3) food
      deprivation leads to increased alcohol intake. METHODS: We randomly assigned AD
      subjects in early abstinence to 3 different sets of dietary instructions (eat
      sweets for alcohol urges; eat a balanced diet; avoid sweets). We compared the
      groups on urges for alcohol, alcohol consumption, weight, and sweet preference at
      baseline, one, and six months. We also compared these AD subjects with light
      drinking C's and compared AD subjects who remained abstinent for 6 month follow
      up with nonabstinent AD subjects. RESULTS: Recruited AS subjects, 38 of 68,
      completed 6 month follow-up; 27 of 36 C's completed the follow-up. 21 AD's were
      abstinent while 17 were non-abstinent. There was no effect of dietary
      recommendations on urges to drink or alcohol consumption. AD's were more likely
      than C's to prefer highly sweet tastants. The proportion of AD's preferring the
      sweetest tastant decreased over time. AD's gained more weight than C's over the 6
      month follow-up. DISCUSSION: While the use of sweets did not affect urges to
      drink or drinking, important relationships between sweet preference, weight gain,
      and alcohol dependence or abstinence were identified.

PMID- 15990242
TI  - The intellectual lineage of paradoxical pharmacology strategy.

PMID- 15990243
TI  - Loss of self-control in intertemporal choice may be attributable to logarithmic
      time-perception.
AB  - Impulsivity and loss of self-control in drug-dependent patients have been
      associated with the manner in which they discount delayed rewards. Although drugs
      of abuse have been shown to modify perceived time-duration, little is known
      regarding the relationship between impulsive decision-making in intertemporal
      choice and estimation of time-duration. In classical economic theory, it has been
      hypothesized that people discount future reward value exponentially. In
      exponential discounting, a temporal discounting rate is constant over time, which
      has been referred to as dynamic consistency. However, accumulating empirical
      evidence in biology, psychopharmacology, behavioral neuroscience, and
      neuroeconomics does not support the hypothesis. Rather, dynamically inconsistent
      manners of discounting delayed rewards, e.g., hyperbolic discounting, have been
      repeatedly observed in humans and non-human animals. In spite of recent advances
      in neuroimaging and neuropsychopharmacological study, the reason why humans and
      animals discount delayed rewards hyperbolically is unknown. In this study, we
      hypothesized that empirically-observed dynamical inconsistency in intertemporal
      choice may result from errors in the perception of time-duration. It is proposed
      that perception of temporal duration following Weber's law might explain the
      dynamical inconsistency. Possible future study directions for elucidating neural
      mechanisms underlying inconsistent intertemporal choice are discussed.

PMID- 15990244
TI  - On the identity of "citers": are papers promptly recognized by other
      investigators?

PMID- 15990245
TI  - Tamoxifen may increase insulin requirement in breast cancer patients with type 1
      diabetes mellitus through its agonistic activity on splenic endothelial cells and
      inhibitory effect on pancreatic beta cells.

PMID- 15990246
TI  - Very late nonfatal consequences of fractionated TBI in children undergoing bone
      marrow transplant.
AB  - PURPOSE: To describe long-term late consequences in children who received total
      body irradiation (TBI) for hematopoietic stem cell transplantation 10 years
      earlier. METHODS AND MATERIALS: A cohort of 42 children treated with TBI between
      1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was
      evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total
      dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice
      daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous
      and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was
      6.3 years, and 18.4 years at most recent follow-up. RESULTS: Cataract was
      diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was
      detected in 12%, whereas thyroid nodules were observed in 60% of our population
      after a median interval of 10.2 years. Patients treated with 990 cGy developed
      thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002).
      Thyroid carcinoma was diagnosed in 14% of the total population. Females who
      received FTBI after menarche more frequently developed temporary ovarian
      dysfunction than those treated before menarche, but cases of persistent ovarian
      dysfunction did not differ between the two groups. Indirect signs of germinal
      testicular dysfunction were detected in 87% of males. Restrictive pulmonary
      disease was observed in 74% of patients. Osteochondroma was found in 29% of
      patients after a median interval of 9.2 years. This latter complication appeared
      more frequently in patients irradiated before the age of 3 years (p < 0.001).
      CONCLUSIONS: This study shows that late effects that are likely permanent,
      although not fatal, are frequent in survivors 10 years after TBI. However, some
      of the side effects observed shortly after TBI either disappeared or remained
      unchanged without signs of evolution. Monitoring is recommended to pursue
      secondary prevention strategies and counseling on family planning.

PMID- 15990247
TI  - Hypofractionated radiotherapy with carbon ion beams for prostate cancer.
AB  - PURPOSE: Analysis of the results of hypofractionated conformal carbon ion
      radiotherapy for localized prostate cancer was performed, with special regard to
      normal tissue morbidity and biochemical relapse-free rate (bNED). METHODS AND
      MATERIALS: Analysis was performed for 201 patients treated with the dose
      fractionation regimen established during three clinical trials performed between
      June 1995 and February 2004. Outcomes were measured in terms of toxicity,
      survival, freedom from local recurrence, and bNED. RESULTS: No Grade 3 or higher
      toxicities were observed in either the rectum or genitourinary system, and the
      incidences of Grade 2 rectum or genitourinary morbidity were only 1.0% and 6.0%,
      respectively. The overall 5-year biochemical relapse-free survival was 83.2%
      without any local recurrence. Gleason score, initial PSA, and T stage were all
      significant prognostic factors for bNED, which was 97.1% in patients with Gleason
      score < or =7 and initial PSA <20 ng/mL. CONCLUSION: Hypofractionated carbon ion
      radiotherapy with the established dose fractionation regimen yielded satisfactory
      bNED without local recurrence and with minimal morbidity. Long-term results are
      necessary to confirm the utility of carbon ion radiotherapy in the treatment of
      localized prostate cancer.

PMID- 15990248
TI  - Visual acuity after Ruthenium(106) brachytherapy of choroidal melanomas.
AB  - PURPOSE: To report on conservation of visual acuity after Ruthenium(106) (Ru-106)
      brachytherapy of choroidal melanoma. METHODS AND MATERIALS: This study was a
      noncomparative interventional case series of 458 patients with choroidal melanoma
      treated at a single center between January 1993 and December 2001. The
      intervention consisted of Ru-106 brachytherapy delivering minimum scleral and
      apex doses of 300 Gy and 80 Gy, respectively, using a 15-mm or 20-mm plaque. For
      discrete, posterior tumors, the plaque was positioned eccentrically with its
      posterior edge aligned with the posterior tumor margin. To ensure correct plaque
      positioning, any overlying extraocular muscles were dis-inserted, and the
      locations of both tumor and plaque edges were confirmed by transillumination and
      indentation. The main outcome measures were conservation of vision of 20/40 or
      better, 20/200 or better, and Counting Fingers or better, according to baseline
      variables. RESULTS: The actuarial rate of conservation of 20/40 or better was 55%
      at 9 years, loss of such vision correlating with posterior tumor extension (p <
      0.001), temporal tumor location (p = 0.001), increased tumor height (p = 0.01),
      and older age (p < 0.01) (Cox multivariate analysis). Similar analyses showed
      conservation of 20/200 or better in 57% of eyes at 9 years, loss correlating with
      reduced initial visual acuity (p < 0.001), posterior tumor extension (p < 0.001),
      and temporal tumor location (p = 0.006). Counting Fingers or better vision was
      conserved in 83% of patients at 9 years, loss correlating with increased tumor
      height (p < 0.0001). Local tumor recurrence occurred in 9 patients (actuarial
      rate, 3% at 9 years). CONCLUSION: Ruthenium(106) brachytherapy of posterior
      choroidal melanoma achieves good conservation of vision if the tumor does not
      extend close to the optic nerve or fovea.

PMID- 15990249
TI  - Vasorelaxant action of aqueous extract of the leaves of Persea americana on
      isolated thoracic rat aorta.
AB  - The present study investigated the vasorelaxant action of the aqueous leaves
      extract of Persea americana on isolated rat aorta. The results showed that the
      extract produced significant vasorelaxation and that the effect is dependent on
      the synthesis or release of endothelium-derived relaxing factors (EDRFs) as well
      as the release of prostanoid. The extract also reduced vasoconstriction probably
      by inhibiting Ca2+ influx through calcium channels.

PMID- 15990250
TI  - A new steroidal saponin from Solanum sisymbriifolium roots.
AB  - Isonuatigenin-3-O-beta-solatriose (1) was isolated from the roots of Solanum
      sisymbriifolium. Its structure was determined by spectroscopic methods.

PMID- 15990251
TI  - Lactobacillus fermentum CRL 722 is able to deliver active alpha-galactosidase
      activity in the small intestine of rats.
AB  - alpha-galactooligosaccharides (alpha-GOS) found in legumes such as soybeans can
      cause gastrointestinal disorders since mammals lack alpha-galactosidase (alpha
      Gal) in the small intestine which is necessary for their hydrolysis.
      Lactobacillus fermentum CRL 722 is a lactic acid bacterium (LAB) capable of
      degrading alpha-GOS due to its elevated alpha-Gal activity. When conventional
      rats were fed live L. fermentum CRL 722 or cell-free extracts of this strain, a
      short-lived alpha-Gal activity was detected in the upper gastrointestinal tract.
      The safety of this LAB was also assessed. L. fermentum CRL 722 could thus be used
      as a vehicle to safely confer alpha-Gal in the small intestine of monogastric
      animal.

PMID- 15990252
TI  - An unexpected role for the putative 4'-phosphopantetheinyl transferase-encoding
      gene nysF in the regulation of nystatin biosynthesis in Streptomyces noursei ATCC
      11455.
AB  - The nysF gene encoding a putative 4'-phosphopantetheinyl transferase (PPTase) is
      located at the 5' border of the nystatin biosynthesis gene cluster in
      Streptomyces noursei. PPTases carry out post-translational modification of the
      acyl carrier protein domains on the polyketide synthases (PKS) required for their
      full functionality, and hence NysF was assumed to be involved in similar
      modification of the nystatin PKS. At the same time, DNA sequence analysis of the
      genomic region adjacent to the nysF gene revealed a gene cluster for a putative
      lantibiotic biosynthesis. This finding created some uncertainty regarding which
      gene cluster nysF functionally belongs to. To resolve this ambiguity, nysF was
      inactivated by both insertion of a kanamycin (Km) resistance marker into its
      coding region, and by in-frame deletion. Surprisingly, the nystatin production in
      both the nysF::Km(R) and DeltanysF mutants increased by ca. 60% compared to the
      wild-type, suggesting a negative role of nysF in the nystatin biosynthesis. The
      expression of xylE reporter gene under control of different promoters from the
      nystatin gene cluster in the DeltanysF mutant was studied. The data obtained
      clearly show enhanced expression of xylE from the promoters of several structural
      and regulatory genes in the DeltanysF mutant, implying that NysF negatively
      regulates the nystatin biosynthesis.

PMID- 15990253
TI  - Characterization of the Escherichia coli O59 and O155 O-antigen gene clusters:
      the atypical wzx genes are evolutionary related.
AB  - O-antigens are highly polymorphic. The genes specifically involved in O-antigen
      synthesis are generally grouped together on the chromosome as a gene cluster. In
      Escherichia coli, the O-antigen gene clusters are characteristically located
      between the housekeeping genes galF and gnd. In this study, the O-antigen gene
      clusters of E. coli O59 and E. coli O155 were sequenced. The former was found to
      contain genes for GDP-mannose synthesis, glycosyltransferase genes and the O
      antigen polymerase gene (wzy), while the latter contained only
      glycosyltransferase genes and wzy. O unit flippase genes (wzx) were found
      immediately downstream of the gnd gene, in the region between the gnd and hisI
      genes in these two strains. This atypical location of wzx has not been reported
      before, and furthermore these two genes complemented in trans despite the fact
      that different O-antigen structures are present in E. coli O59 and O155. A
      putative acetyltransferase gene was found downstream of wzx in both strains.
      Comparison of the region between gnd and hisI revealed that the wzx and
      acetyltransferase genes are closely related between E. coli O59 and O155,
      indicating that the two gene clusters arose recently from a common ancestor. This
      work provides further evidence for the O-antigen gene cluster having formed
      gradually, and selection pressure will eventually bring O-antigen genes into a
      single cluster. Genes specific for E. coli O59 and O155, respectively, were also
      identified.

PMID- 15990254
TI  - Effect of heat-shock and bile salts on protein synthesis of Bifidobacterium
      longum revealed by [35S]methionine labelling and two-dimensional gel
      electrophoresis.
AB  - Experimental conditions for efficient protein radiolabelling and two-dimensional
      gel electrophoresis were developed for Bifidobacterium longum. Using these tools,
      protein synthesis in cells before and after heat-shock and bile salts treatment
      was investigated. Following heat-stress, 13 proteins were upregulated, of which
      HtrA, DnaK and GroEL were also moderately induced by bile salts, indicating close
      relationship between the heat and bile salts responses in bifidobacteria. Our
      work indicated that, as a consequence of prolonged heat-stress, HtrA undergoes
      sequential modification and proteolysis, and that this mechanism could be
      employed by bifidobacteria to respond to heat-stress.

PMID- 15990255
TI  - Developing a genetic system for functional manipulations of FUM1, a polyketide
      synthase gene for the biosynthesis of fumonisins in Fusarium verticillioides.
AB  - Fumonisins are mycotoxins produced by Fusarium verticillioides, a filamentous
      fungus that is a widespread pathogen of corn. The biosynthesis of fumonisins is
      catalyzed by an iterative modular polyketide synthase (PKS). The study of the
      biosynthetic mechanism for these reduced fungal polyketides has been challenging
      due to the difficulties in detecting the intermediates with a linear carbon chain
      and manipulating the 7-domain PKS gene from the filamentous fungus. Here, we
      described the development of a genetic system for functionally manipulating the
      methyltransferase domain of FUM1 that is responsible for the assembly of a
      dimethylated 18-carbon chain. Using a two-stage screening strategy, including
      both positive and negative screenings, we were able to generate mutant strains
      with a specifically changed active-site in FUM1. LC-MS analyses indicated that
      biosynthetic intermediates were detectable in the early stage of culture. The
      results represent the first functional manipulation of the PKS involved in the
      biosynthesis of fumonisins.

PMID- 15990256
TI  - Endocrine, morphological, and cytological effects of a depot GnRH agonist in
      bovine.
AB  - The present study was conducted to assess effects of the gonadotropin-releasing
      hormone agonist (GnRHa) triptorelin in dairy heifers. The peptide was released
      from a commercial 4-week depot formulation (Decapeptyl Depot) administered at
      animals' estrus (day 0). First experiment (EXP I, n=5), which was aimed to
      explore the availability of peptide, detected a maximum of triptorelin
      concentration between day 2 and 5 after depot injection, and the peptide remained
      detectable by RIA in peripheral blood for about 3 weeks. In further experiments,
      the peptide release was terminated on day 9 (EXP II, n=16) or day 21 (EXP III,
      n=47). Treatment effects were studied on follicular development, the
      characteristics of cumulus-oocyte complexes (COCs) (EXP II; EXP IIIa) and
      secretions of LH and progesterone (EXP IIIb). Results showed that the occurrence
      of the pre-ovulatory LH surge was more uniform in treated heifers than that in
      controls. The duration of ovulation periods was similar amongst the heifers of
      EXP II, but more compact amongst those of EXP III each compared with the
      respective controls. Post-ovulatory, the number of LH pulses was significantly
      reduced by treatment, whereas both basal LH and progesterone concentrations were
      elevated on a few days. Follicular growth was reduced only by the prolonged
      influence of the GnRHa. There were increased proportions of both degenerated COCs
      and immature oocytes from small follicles (<3mm in diameter), and meiotic
      configuration and quality of oocytes isolated from follicles 3-5mm were changed
      after the prolonged, 21-day treatment. These results indicate that a continuous
      influence of a GnRHa over more than 1 week may increasingly impair the
      development of bovine follicles and oocytes. This may have some significance for
      the development of novel GnRH-based techniques in regulating the reproductive
      function in cattle.

PMID- 15990257
TI  - Effects of estrogen, raloxifene, and hormone replacement therapy on serum C
      reactive protein and homocysteine levels.
AB  - OBJECTIVES: To investigate the effects of conjugated equine estrogen (CEE), CEE
      plus medroxyprogesterone acetate (MPA), CEE plus Nomegestrol acetate (NA), and
      raloxifene on serum high sensitivity C-reactive protein (hs-CRP) and homocysteine
      (Hcy) levels in healthy postmenopausal women. MATERIALS: One hundred seven
      healthy postmenopausal women were recruited in a prospective, randomized, and
      placebo-controlled 6 months study. Of these, 18 were hysterectomized and received
      daily oral 0.625 mg CEE. Eighty nine non-hysterectomized women were randomly
      allocated to one of four groups: a group (22 patients) treated with CEE, 0.625
      mg/daily plus MPA 2.5 mg/daily; a group (22 patients) treated with CEE, 0.625
      mg/daily plus NA 5 mg/daily; a group (23 patients) treated with raloxifene
      hydrochloride, 60 mg once daily; and a placebo group (22 patients). Hcy and hs
      CRP were measured at baseline and at 3 and 6 months. RESULTS: CEE (20%, P=0.03)
      and CEE+MPA (59%, P=0.006) increased serum hs-CRP levels significantly, whereas
      CEE+NA decreased serum hs-CRP by 25% (P=0.01). Raloxifene had no significant
      effect on serum hs-CRP levels during and after the treatment. In all active
      treatment groups serum Hcy levels decreased significantly compared to baseline
      and placebo. CONCLUSIONS: Conjugated equine estrogen, hormone replacement
      therapies, and raloxifene lower serum Hcy levels to a comparable extent in
      postmenopausal women. Hs-CRP, as a cardiovascular risk factor, is not influenced
      by raloxifene, whereas CEE and CEE plus MPA significantly increase hs-CRP levels.
      Treatment with CEE plus NA reduces serum hs-CRP levels.

PMID- 15990258
TI  - Comparative study and optimisation of the administration mode of three proton
      pump inhibitors by nasogastric tube.
AB  - Patients in intensive care often develop stress-induced ulcers. As a preventive
      measure, proton pump inhibitors (PPIs) are administered by nasogastric tube.
      However, some PPIs can block the tube. The aim of this study was to compare the
      behaviour of three PPIs (omeprazole, lanzoprazole and esomeprazole) during the
      transit of the granules through the tube and to optimise their modes of
      administration. For each IPP, the experiment was designed to study the influence
      of four variables: the tube material (silicone or polyurethane), the solvent used
      to dilute the granules (water or apple juice), the mode of administration (in two
      or three doses) and the rinse volume (10 or 20 ml). We counted the granules
      before transit and at the tube outlet, and assayed the active drug ingredient by
      UV spectrometry. The assay showed complete transit of esomeprazole through the
      tube, but average losses of omeprazole and lanzoprazole of 39 and 33%,
      respectively, were observed. No significant improvement was obtained by the
      variables 'diluent' and 'mode of administration'. The variable 'rinse' had a
      significant influence. For lanzoprazole, a polyurethane tube allowed recovery of
      on average 86% of the active ingredient. Esomeprazole is thus the choice PPI for
      the treatment of patients by nasogastric tube. Using a polyurethane tube and a
      rinse volume of 20 ml, the administration of lanzoprazole by tube can be
      considered. Use of omeprazole is not recommended because none of the modes of
      administration tested ensured that a sufficient concentration of active
      ingredient reached the stomach.

PMID- 15990259
TI  - Antioxidant activity of Aporosa lindleyana root.
AB  - Four successive and two crude extracts of Aporosa lindleyana Baill. root were
      tested for antioxidant activity using standard in vitro and in vivo models. The
      successive methanol and ethyl acetate and crude 50% methanol extracts showed
      antioxidant activity with IC50 values 3.51+/-0.27, 6.09+/-1.00 and 7.34+/-0.46
      microg/ml, respectively, in DPPH method. In the nitric oxide radical inhibition
      method, the successive ethyl acetate, petroleum ether and methanol extracts
      showed antioxidant activity. The successive methanol extract at 100 and 200 mg/kg
      body weight administered for 5 days prior to CCl4 treatment caused a significant
      increase in the levels of catalase and SOD and a significant decrease in the
      level of TBARS in liver, kidney and blood, when compared to CCl4 treated control.
      These results indicate strong antioxidant nature of Aporosa lindleyana root. The
      in vitro cytotoxicity studies against normal Vero cell lines indicate non-toxic
      nature of the root extracts. The study provides a proof for the ethnomedical and
      reported biological activities.

PMID- 15990260
TI  - Hypoglycemic effect of Malmea depressa root on streptozotocin diabetic rats.
AB  - The hypoglycemic effects of water, ethanolic and butanolic extracts prepared from
      the root of Malmea depressa (Baill) R.E. Fries. (Annonaceae) were studied in
      diabetic rats (streptozotocin induced). Oral application of water extracts at
      doses of 40 and 80 mg/kg, ethanolic (112 mg/kg) and butanolic (80 mg/kg) extracts
      significantly lowered the plasma glucose levels in diabetic rats within three
      hours. Glibenclamide and metformin were used as references and showed similar
      hypoglycemic effects like the extracts. The three extracts have a similar
      chemical composition (HPLC analysis).

PMID- 15990261
TI  - Prehistoric peyote use: alkaloid analysis and radiocarbon dating of
      archaeological specimens of Lophophora from Texas.
AB  - Two archaeological specimens of peyote buttons, i.e. dried tops of the cactus
      Lophophora williamsii (Lem.) Coulter, from the collection of the Witte Museum in
      San Antonio, was subjected to radiocarbon dating and alkaloid analysis. The
      samples were presumably found in Shumla Cave No. 5 on the Rio Grande, Texas.
      Radiocarbon dating shows that the calibrated 14C age of the weighted mean of the
      two individual dated samples corresponds to the calendric time interval 3780-3660
      BC (one sigma significance). Alkaloid extraction yielded approximately 2% of
      alkaloids. Analysis with thin-layer chromatography (TLC) and gas chromatography
      mass spectrometry (GC-MS) led to the identification of mescaline in both samples.
      No other peyote alkaloids could be identified. The two peyote samples appear to
      be the oldest plant drug ever to yield a major bioactive compound upon chemical
      analysis. The identification of mescaline strengthens the evidence that native
      North Americans recognized the psychotropic properties of peyote as long as 5700
      years ago.

PMID- 15990262
TI  - Estimation of stature and determination of sex from radial and ulnar bone lengths
      in a Turkish corpse sample.
AB  - Determination of sex and estimation of stature are important aspects of forensic
      identification of an unknown individual. In the absence of pelvis the sex is
      assessed from long bones and cranium as they both provide high accuracy in
      sexing. The present study is an attempt to assess sex and stature from long bones
      of the forearm using recently deceased forensic cases in Istanbul, Turkey. The
      sample is composed of 80 males and 47 females with an average age of 36 and 30
      years, respectively. Length measurements from the radius and ulna were obtained
      by exposing the epiphyseal ends of the long bones in a fashion similar to dry
      long bones. Discriminant function statistics showed a sex determination accuracy
      as high as 96%. Regression analysis was used in stature estimation from these two
      bones. Ideally osteological remains are necessary to make standards for
      osteological identification. These materials are not always easy to obtain and
      those available seem to be less ideal when they do not represent a current
      population. Forensic anthropologists therefore should develop techniques that
      utilize autopsy remains.

PMID- 15990263
TI  - Y-chromosomal STR haplotypes in Sicily.
AB  - Eight Y-chromosomal short tandem repeats (STRs)-DYS19, DYS389-I, DYS389-II,
      DYS390, DYS391, DYS392, DYS393 and DYS385-were typed in a population sample
      (n=255) of unrelated Sicilian males from nine different towns on the main island
      and from the island of Pantelleria.

PMID- 15990264
TI  - Forensic genetic analysis of mitochondrial DNA hypervariable region I/II
      sequences: an expanded Korean population database.
AB  - We have analyzed variation of the mitochondrial DNA (mtDNA) hypervariable
      segments I and II (HVS-I and HVS-II) in 185 randomly chosen individuals from
      Korea to provide an expanded and reliable Korean database. Combined sequence
      comparison of HVS-I and HVS-II led to the identification of 167 different
      haplotypes characterized by 154 variable sites. One hundred and fifty-one of the
      haplotypes were individual-specific, 14 were found in two individuals and 2 were
      found in three individuals. A pairwise comparison of the 185 HVS-I/II sequences
      found an average of 10.11 +/- 4.63 differences between individuals. The random
      match probability and gene diversity for the combined hypervariable regions were
      estimated at 0.66% and 0.9988, respectively. Analyzing the expanded database
      including three previously reported data sets and the present data using
      haplogroup-based comparisons and comparison with closely related sequences
      allowed errors to be detected and eliminated, thus considerably improving data
      quality. Sample division comparisons based on PhiST genetic distance measures
      revealed no significant population differentiation in the distribution of mtDNA
      sequence variations between the present data set and a database in The Scientific
      Working Group on DNA Analysis Methods (SWGDAM), but did indicate differences from
      other sets of data. Based on the results of mtDNA profiles, almost all of the
      mtDNA types studied here could be classified into subsets of haplogroups common
      in east Asia, and show that the Koreans possess lineages from both the southern
      and the northern haplogroup complexes of east Asian populations. The new data,
      combined with other mtDNA sequences, demonstrate how useful comparison with
      closely related mtDNA sequences can be for improving database quality, as well as
      providing haplotype information for forensic and population genetic analyses in
      the Korean population.

PMID- 15990265
TI  - A study of spectral integration and normalization in NMR-based metabonomic
      analyses.
AB  - Metabonomics involves the quantitation of the dynamic multivariate metabolic
      response of an organism to a pathological event or genetic modification [J.K.
      Nicholson, J.C. Lindon, E. Holmes, Xenobiotica 29 (1999) 1181-1189]. The analysis
      of these data involves the use of appropriate multivariate statistical methods;
      Principal Component Analysis (PCA) has been documented as a valuable pattern
      recognition technique for 1H NMR spectral data [J.T. Brindle, H. Antti, E.
      Holmes, G. Tranter, J.K. Nicholson, H.W. Bethell, S. Clarke, P.M. Schofield, E.
      McKilligin, D.E. Mosedale, D.J. Grainger, Nat. Med. 8 (2002) 1439-1444; B.C.
      Potts, A.J. Deese, G.J. Stevens, M.D. Reily, D.G. Robertson, J. Theiss, J. Pharm.
      Biomed. Anal. 26 (2001) 463-476; D.G. Robertson, M.D. Reily, R.E. Sigler, D.F.
      Wells, D.A. Paterson, T.K. Braden, Toxicol. Sci. 57 (2000) 326-337; L.C. Robosky,
      D.G. Robertson, J.D. Baker, S. Rane, M.D. Reily, Comb. Chem. High Throughput
      Screen. 5 (2002) 651-662]. Prior to PCA the raw data is typically processed
      through four steps; (1) baseline correction, (2) endogenous peak removal, (3)
      integration over spectral regions to reduce the number of variables, and (4)
      normalization. The effect of the size of spectral integration regions and
      normalization has not been well studied. The variability structure and
      classification accuracy on two distinctly different datasets are assessed via PCA
      and a leave-one-out cross-validation approach under two normalization approaches
      and an array of spectral integration regions. The first dataset consists of urine
      from 15 male Wistar-Hannover rats dosed with ANIT measured at five time points,
      mimicking drug-induced cholangiolitic hepatitis [D.G. Robertson, M.D. Reily, R.E.
      Sigler, D.F. Wells, D.A. Paterson, T.K. Braden, Toxicol. Sci. 57 (2000) 326-337;
      J.P. Shockcor, E. Holmes, Curr. Top. Med. Chem. 2 (2002) 35-51; N.J. Waters, E.
      Holmes, A. Williams, C.J. Waterfield, R.D. Farrant, J.K. Nicholson, Chem. Res.
      Toxicol. 14 (2001) 1401-1412]. The second data is serum samples from young male
      C57BL/6 mice subjected to instillation of pancreatic elastase producing emphysema
      type symptoms [C. Kuhn, S.Y. Yu, M. Chraplyvy, H.E. Linder, R.M. Senior, Lab.
      Invest. 34 (1976) 372-380; C. Kuhn, R.M. Senior, Lung 155 (1978) 185-197]. This
      study indicates that independent of the normalization method the classification
      accuracy achieved from metabonomic studies is not highly sensitive to the size of
      the spectral integration region. Additionally, both datasets scaled to mean zero
      and unity variance (auto-scaled) have higher variability within classification
      accuracy over spectral integration window widths than data scaled to the total
      intensity of the spectrum. Of the top 10 latent variables for the ANIT dataset
      the auto-scale normalization has standard deviations larger than the total-scale
      in seven cases. In the case of the elastase all standard deviations are larger
      for the auto-scaling.

PMID- 15990266
TI  - Capillary electrophoretic method for the determination of diterpenoid isomers in
      Acanthopanax species.
AB  - Acanthoic, continentalic and kaurenoic acids are bioactive diterpenoids that are
      structural isomers isolated from Acanthopanax species. Due to the interest in
      their potent biological activity, an analytical method of diterpenoids was
      developed for the quality control and the classification of Acanthopanax species.
      Capillary electrophoresis was used to separate and quantify the isomers. The
      three compounds were successfully separated from each other and from the matrices
      in the extracts of leaves, stems and roots of Acanthopanax species. The contents
      of acanthoic, continentalic and kaurenoic acids showed taxonomical differences in
      Acanthopanax species. Relatively higher concentrations of diterpenoids were found
      from A. koreanum and A. trifoliatus, while only trace amounts were found from the
      four other species tested: A. senticosus, A. senticosus f. inermis, A.
      chiisanensis, and A. divaricatus var. albeofructus. The contents of diterpenoids
      in association with lignans and triterpenoids in the Acanthopanax species could
      provide a chemotaxonomical index able to be used in the classification and
      discrimination of the species.

PMID- 15990267
TI  - Kinetics of beta-lactam antibiotics synthesis by penicillin G acylase (PGA) from
      the viewpoint of the industrial enzymatic reactor optimization.
AB  - Competition with well-established, fine-tuned chemical processes is a major
      challenge for the industrial implementation of the enzymatic synthesis of beta
      lactam antibiotics. Enzyme-based routes are acknowledged as an environmental
      friendly approach, avoiding organochloride solvents and working at room
      temperatures. Among different alternatives, the kinetically controlled synthesis,
      using immobilized penicillin G acylase (PGA) in aqueous environment, with the
      simultaneous crystallization of the product, is the most promising one. However,
      PGA may act either as a transferase or as a hydrolase, catalyzing two undesired
      side reactions: the hydrolysis of the acyl side-chain precursor (an ester or
      amide, a parallel reaction) and the hydrolysis of the antibiotic itself (a
      consecutive reaction). This review focuses specially on aspects of the reactions'
      kinetics that may affect the performance of the enzymatic reactor.

PMID- 15990268
TI  - Evaluation of a communication and stress management training programme for
      infertile couples.
AB  - OBJECTIVE: This study evaluates a patient education programme focussed on
      improving communication and stress management skills among couples in fertility
      treatment. METHODS: In total, 37 couples completed the intervention. Two teachers
      conducted all the five courses offered. The effectiveness regarding communication
      and infertility-related stress was assessed by questionnaires immediately before
      (time T1) and after the intervention (time T2). Seeking of information and
      professional support was assessed at a 12-month follow-up (time T3); response
      rates were: T1, 93.2%; T2, 85.1%; T3, 74.3%. Data were compared at baseline (T1)
      and at the 12-month follow-up (T3) with a prospective cohort of Danish people in
      fertility treatment. RESULTS: There were no differences in infertility-related
      stress at base line between the two groups studied. We estimated the bi
      directional changes in communication, e.g., changes from talking often to talking
      less frequently and vice versa. More intervention participants started to talk
      often with their partner about infertility and its treatment after the
      intervention compared to those who stopped to talk often. Women and men changed
      occurrence, frequency and content of communication with close other people. Among
      women marital benefit increased significantly. Infertility-related stress was not
      reduced significantly. Significantly more intervention participants than in the
      comparison group had contacted support groups, a psychologist and/or agencies for
      adoption at the 12-month follow-up. CONCLUSION: The intervention resulted in
      important perceived improvement in the participants' competence to actively
      manage changes in marital communication and in communication in different social
      arenas. PRACTICE IMPLICATIONS: We recommend fertility clinics to develop and
      evaluate different interventions for those fertility couples who ask for more
      psychosocial support.

PMID- 15990269
TI  - The temporal stability of cluster and switch scores using a modified COWAT
      procedure.
AB  - This study examined the impact of instructional changes on the temporal stability
      of cluster and switch scores for the Controlled Oral Word Association Test
      [COWAT; Benton, A. L., Hamsher, K., & Sivan, A. B. (1994). Multilingual Aphasia
      Examination (3rd ed.). Iowa City, IA: AJA Associates]. Healthy undergraduates
      were assigned randomly into experimental (N = 60) and control (N = 60) groups.
      Experimental group participants were administered three letters as customary,
      then informed about clustering strategies prior to completing three additional
      letters. Control group participants received the original instructions only for
      all six letters. All participants were examined on two separate occasions. The
      mean inter-assessment interval was 38.6 days (ranging from 29 to 47 days).
      Stability coefficients for cluster and switch scores on the last set of letters
      differed significantly between groups, as higher coefficients were observed for
      the experimental group. In contrast, stability coefficients for the total words
      produced and mean cluster size did not differ between groups. Although the
      temporal stability improved, the resulting coefficients were modest (e.g., r(icc)
      = .76 for clusters; r(icc) = .79 for switches). We present implications of these
      findings and considerations for future research.

PMID- 15990270
TI  - Identification of two evolutionarily conserved and functional regulatory elements
      in intron 2 of the human BRCA1 gene.
AB  - Cross-species comparative genomics is a powerful strategy for identifying
      functional regulatory elements within noncoding DNA. In this paper, comparative
      analysis of human and mouse intronic sequences in the breast cancer
      susceptibility gene (BRCA1) revealed two evolutionarily conserved noncoding
      sequences (CNS) in intron 2, 5 kb downstream of the core BRCA1 promoter. The
      functionality of these elements was examined using homologous-recombination-based
      mutagenesis of reporter gene-tagged cosmids incorporating these regions and
      flanking sequences from the BRCA1 locus. This showed that CNS-1 and CNS-2 have
      differential transcriptional regulatory activity in epithelial cell lines.
      Mutation of CNS-1 significantly reduced reporter gene expression to 30% of
      control levels. Conversely mutation of CNS-2 increased expression to 200% of
      control levels. Regulation is at the level of transcription and shows promoter
      specificity. Both elements also specifically bind nuclear proteins in vitro.
      These studies demonstrate that the combination of comparative genomics and
      functional analysis is a successful strategy to identify novel regulatory
      elements and provide the first direct evidence that conserved noncoding sequences
      in BRCA1 regulate gene expression.

PMID- 15990271
TI  - M-mode color Doppler ultrasonic imaging of vertical tongue movement during
      articulatory movement.
AB  - To observe and estimate the movement of the tongue, ultrasonic investigation is
      the most harmless real-time monitoring procedure for analyzing articulatory
      movements. Color Doppler ultrasonic imaging is special in that it can only sample
      a moving target, and it can indicate the velocity and direction of the target by
      color and brightness in real time. This study assessed and demonstrated the
      validity of M-mode color Doppler ultrasonic imaging to observe the movements of
      the tongue during syllable repetition tasks performed by normal subjects and
      dysarthric patients, those affected by amyotrophic lateral sclerosis, cerebellar
      ataxia, Parkinsonism, and polymyopathy. When the transducer was set below the
      jaw, upward movement was indicated by a blue signal and downward movement was
      indicated by a red one on the screen of the ultrasound machine. We also measured
      the velocity of the tongue by contrast scale classified by 15 degrees. Thus, we
      could observe vertical tongue movement by a color-coded pattern after
      quantitative analysis. The Doppler signal patterns of normal subjects were
      verified by simultaneous video x-ray fluorography recordings. The findings for
      dysarthric patients corresponded well with previously reported features analyzed
      by other methods. Therefore, color Doppler ultrasonic imaging of the tongue is a
      useful procedure to researchers for clinical speech and voice studies.

PMID- 15990272
TI  - Throaty voice quality: subglottal pressure, voice source, and formant
      characteristics.
AB  - "Throaty" voice quality has been regarded by voice pedagogues as undesired and
      even harmful. This study attempts to identify acoustic and physiological
      correlates of this quality. One male and one female subject read a text
      habitually and with a throaty voice quality. Oral pressure during p-occlusion was
      measured as an estimate of subglottal pressure. Long-term average spectrum
      analysis described the average spectrum characteristics. Sixteen syllables,
      perceptually evaluated with regard to throaty quality by five experts, were
      selected for analysis. Formant frequencies and voice source characteristics were
      measured by means of inverse filtering, and the vocal tract shape of the throaty
      and normal versions of the vowels [a,u,i,ae] of the male subject were recorded by
      magnetic resonance imaging. From this material, area functions were derived and
      their resonance frequencies were determined. The throaty versions of these four
      vowels all showed a pharynx that was narrower than in the habitually produced
      versions. To test the relevance of formant frequencies to perceived throaty
      quality, experts rated degree of throatiness in synthetic vowel samples, in which
      the measured formant frequency values of the subject were used. The main acoustic
      correlates of throatiness seemed to be an increase of F1, a decrease of F4, and
      in front vowels a decrease of F2, which presumably results from a narrowing of
      the pharynx. In the male subject, voice source parameters suggested a more
      hyperfunctional voice in throaty samples.

PMID- 15990273
TI  - Fundamental frequency in monolingual English, bilingual English/Russian, and
      bilingual English/Cantonese young adult women.
AB  - Mean F0 of nine young adult English/Russian female bilinguals and nine young
      adult English/Cantonese female bilinguals were examined from samples of connected
      speech in each language. Mean F0 were compared in each language and in English
      with those of a monolingual English control group of ten young adult female
      speakers. Acoustic measurements were analyzed with the Kay Elemetrics Multispeech
      program (Kay Elemetrics, Lincoln Park, NJ). The results indicate that the
      English/Russian bilinguals consistently had a higher mean F0 in Russian than in
      English. Mean F0 did not change with language switch for the English/Cantonese
      speakers. There were no significant differences between the groups in their
      English production. Clinical implications regarding norms for both monolingual
      and bilingual persons, as well as implications for understanding the nature of
      bilingualism, in particular code-switching, are discussed.

PMID- 15990274
TI  - A novel information geometric approach to variable selection in MLP networks.
AB  - In this paper, a novel information geometric-based variable selection criterion
      for multi-layer perceptron networks is described. It is based on projections of
      the Riemannian manifold defined by a multi-layer perceptron network on
      submanifolds defined by multi-layer perceptron networks with reduced input
      dimension. We show how the divergence between models can be used as a criterion
      for an efficient search in the space of networks with different inputs. Then, we
      show how the posterior probabilities of the models can be evaluated to rank the
      projected models. Finally, we test our algorithm on synthetic and real data, and
      compare its performances with other methods reported in literature.

PMID- 15990275
TI  - Modelling brain emergent behaviours through coevolution of neural agents.
AB  - Recently, many research efforts focus on modelling partial brain areas with the
      long-term goal to support cognitive abilities of artificial organisms. Existing
      models usually suffer from heterogeneity, which constitutes their integration
      very difficult. The present work introduces a computational framework to address
      brain modelling tasks, emphasizing on the integrative performance of
      substructures. Moreover, implemented models are embedded in a robotic platform to
      support its behavioural capabilities. We follow an agent-based approach in the
      design of substructures to support the autonomy of partial brain structures.
      Agents are formulated to allow the emergence of a desired behaviour after a
      certain amount of interaction with the environment. An appropriate collaborative
      coevolutionary algorithm, able to emphasize both the speciality of brain areas
      and their cooperative performance, is employed to support design specification of
      agent structures. The effectiveness of the proposed approach is illustrated
      through the implementation of computational models for motor cortex and
      hippocampus, which are successfully tested on a simulated mobile robot.

PMID- 15990276
TI  - Using ICA for removal of ocular artifacts in EEG recorded from blind subjects.
AB  - One of the standard applications of Independent Component Analysis (ICA) to EEG
      is removal of artifacts due to movements of the eye bulbs. Short blinks as well
      as slower saccadic movements are removed by subtracting respective independent
      components (ICs). EEG recorded from blind subjects poses special problems, since
      it shows a higher quantity of eye movements, which are also more irregular and
      very different across subjects. It is demonstrated that ICA can still be of use
      by comparing results from four blind subjects with results from one subject
      without eye bulbs who therefore does not show eye movement artifacts at all.

PMID- 15990277
TI  - Functional mapping and identification of novel regulators for the
      Toll/Interleukin-1 signalling network by transcription expression cloning.
AB  - Sustained inflammatory responses are central to the development and progression
      of chronic diseases, including atherosclerosis and rheumatoid arthritis. A large
      number of stimuli initiate inflammation by acting on Toll-Interleukin-1 related
      (TIR) domain containing receptors, producing multiple second messengers and
      thence large scale transcriptional changes. The mechanism by which this
      activation occurs is complex, and the continuing isolation of novel pathway
      components, mostly based on sequence similarities and protein-protein interaction
      studies, suggests that many elements of the TIR-initiated signalling network
      remain to be identified. Here we use a new technique, allowing identification of
      components based on function. We report the performance of the screen, our
      identification of human tribbles as a novel protein family regulating
      inflammatory signalling networks, and the detection of ten other components with
      poorly characterized roles in inflammatory signalling pathways. In total, we have
      identified 28 signalling molecules of diverse molecular mechanism by screening
      11% of a cDNA library for the ability to modulation expression of human IL-8, and
      other molecules remain to be followed up. The results suggest that the number of
      human genes involved in IL-8 induction pathways exceed 100. The isolation of
      signalling components by the approach we describe allows detection of new classes
      of signalling components independent of existing techniques for doing so; it is
      simple and robust, and constitutes a general method for mapping signal
      transduction systems controlling gene expression.

PMID- 15990278
TI  - Differences in signaling pathways and expression level of the phosphoinositide
      phosphatase SHIP1 between two oncogenic mutants of the receptor tyrosine kinase
      KIT.
AB  - Oncogenic mutations of the receptor tyrosine kinase KIT are encountered in
      myeloid leukemia and various solid tumors, including gastrointestinal stromal
      tumors. We previously identified the human oncogenic germ line mutant KIT(K642E),
      a substitution in the tyrosine kinase 1 domain (TK1D) in a familial form of
      gastrointestinal stromal tumors. The effects of oncogenic KIT mutants on cell
      signaling and regulation are complex. Cellular models are valuable basic tools to
      tailor novel strategies on specific cellular and molecular bases for tumors
      expressing KIT oncogenic mutants. Murine KIT(WT) and the murine homologues of
      human KIT oncogenic mutants, further referred to as KIT(K641E) and KIT(del559), a
      point deletion in the juxtamembrane domain (JMD), were stably expressed in IL-3
      dependent Ba/F3 cells. Major differences in the constitutively activation of
      Akt/PKB, MAP kinases and STATs pathways were observed between KIT(K641E) and
      KIT(del559), whereas KIT ligand elicited responses in both mutants. Noteworthy,
      the protein level of the phosphoinositide phosphatase SHIP1, but not SHIP2 and
      PTEN, was reduced in KIT(K641E) only while inhibition of KIT phosphorylation
      reversibly raised SHIP1 level in both JMD and TK1D oncogenic mutants, unraveling
      the control of SHIP protein level by KIT phosphorylation.

PMID- 15990279
TI  - Alterations of basement membrane zone in autoimmune subepidermal bullous
      diseases.
AB  - BACKGROUND: Pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis
      bullosa acquisita (EBA) are characterized by the presence of in vivo bound and
      circulating anti-basement membrane zone (BMZ) antibodies directed against
      different antigens localized in the upper part of the lamina lucida, lamina
      lucida-lamina densa border and in sublamina densa region, respectively. The
      alterations of BMZ lead to blister formation. OBJECTIVES: The aim of the present
      study was to compare the alterations of various regions of the BMZ in BP, MMP and
      EBA using laser scanning confocal microscopy (LSCM). METHODS: Biopsy specimens
      taken from perilesional patients' skin were cut into 40mum thick slides, followed
      by double immunofluorescence labeling with antibodies against different BMZ
      structures and anti-human IgG antibody. Three-dimensional reconstruction (3DR) of
      various regions of BMZ and of in vivo bound IgG was performed by computer program
      integrated with LSCM. RESULTS: In BP and MMP, LSCM studies revealed numerous
      invaginations of BMZ, most pronounced at the level of lamina lucida. Integrity of
      BMZ was preserved at the level of lamina lucida, lamina densa and sublamina
      densa. In EBA, continuity of lamina lucida was preserved and numerous
      invaginations were present. More pronounced invaginations of BMZ were observed at
      the level of lamina densa, whereas at the level of the sublamina densa region the
      staining along BMZ was discontinuous. Moreover, large clumps composed of collagen
      VII vertically oriented to the dermal-epidermal junction extending into the mid
      dermis were observed. CONCLUSIONS: The study showed that alterations of BMZ in BP
      and MMP occur mainly in the lamina lucida, and in EBA in the sublamina densa
      region. These alterations in various regions of BMZ in BP, MMP and EBA could be
      responsible for the differences in the level of blister formation and in the
      clinical course of the diseases.

PMID- 15990280
TI  - No modulatory effect of neurokinin-1 receptor antagonists on serotonin uptake in
      human and rat brain synaptosomes.
AB  - Some studies have demonstrated antidepressant activity of neurokinin-1-receptor
      antagonists (NK-1-RA) in major depressive disorder. However, the underlying
      mechanisms of this antidepressant effect are largely unknown. Preclinical studies
      in rats and mice have suggested that NK-1-RA do increase the neuronal release of
      serotonin (5-HT). This, however, seems to be compensated by an increased 5-HT
      reuptake, indicating that NK-1-RA have no inhibitory effect on the 5-HT
      transporter in rodents. Given the possibility that modulation of neurotransmitter
      release and reuptake may differ between species, with major differences found
      between rodents and humans, we investigated for the first time the possible
      modulatory effect of NK-1-RA on 5-HT uptake in human brain synaptosomes and
      compared it with the situation in rat cortex. We found that the specific human NK
      1-RA L-733060, in contrast to the SSRI fluvoxamine (IC50=10(-7.96)M) did not
      inhibit 5-HT uptake in human brain synaptosomes and did not modulate fluvoxamine
      induced 5-HT uptake inhibition at 1 muM. Furthermore, substance P as well as
      Sar9Met(O2)11SP, as the major agonists at the NK-1-R, did not modulate 5-HT
      uptake in human brain synaptosomes. Similar results were found in rat cortex
      synaptosomes by using the rat-specific NK-1-RA WIN51708. These results show that
      in humans, as in rodents, inhibition of the 5-HT transporter is probably not the
      underlying mechanism of the assumed antidepressant activity of NK-1-RA.

PMID- 15990281
TI  - A new cancer diagnostic system based on a CDK profiling technology.
AB  - A series of molecular pathological investigations of the molecules that stimulate
      the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous
      accumulation of knowledge of the clinical significance of these molecules for
      cancer diagnosis. However, the molecules have yet to be applied to clinical
      cancer diagnosis, as there is no available technology for application of the
      knowledge in a clinical setting. We hypothesized that the direct measurement of
      CDK activities and expressions (CDK profiling) might produce clinically relevant
      values for the diagnosis. This study investigated the clinical relevance of CDK
      profiling in gastrointestinal carcinoma tissues by using originally developed
      expression and activity analysis methods. We have established novel methods and
      an apparatus for analyzing the expression and activities of the CDK molecules in
      lysate of tumor tissue in a clinical setting, and examined 30 surgically
      dissected gastrointestinal carcinomas and corresponding normal mucosal specimens.
      We demonstrate here that remarkably elevated CDK2 activity is evident in more
      than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately
      mirrored the differences in proliferation between tumor and normal colonic
      tissues. Our results suggest that CDK profiling is a potent molecular-clinical
      approach to complement the conventional pathological diagnosis, and to further
      assist in the individualized medications.

PMID- 15990282
TI  - The time course of off-line motor sequence learning.
AB  - The acquisition of motor skill occurs with practice, but skill can also increase
      between sessions, a process termed "off-line learning". Here, we investigated the
      amount of time required for the off-line development of skills. Participants were
      tested on an implicit version of the Serial Reaction Time Task and re-tested 1, 4
      or 12 h later. Only those re-tested 4 h or 12 h after initial testing showed off
      line improvements. This demonstrates that implicitly acquired skills can increase
      between sessions and the process occurs over hours.

PMID- 15990283
TI  - Crystallization behavior of supercooled smectic cholesteryl myristate
      nanoparticles containing phospholipids as stabilizers.
AB  - Supercooled smectic nanoparticles based on physiological cholesterol esters are
      under investigation as a potential novel carrier system for lipophilic drugs. The
      present study investigates the very complex crystallization behavior of such
      nanoparticles stabilized with the aid of phospholipids. Phospholipid and
      phospholipid/bile salt stabilized cholesteryl myristate dispersions were prepared
      by high-pressure melt homogenization and characterized by particle size
      measurements, differential scanning calorimetry, X-ray diffraction and electron
      microscopy. To obtain fractions with very small smectic nanoparticles, selected
      dispersions were ultracentrifuged. A mixture of cholesteryl myristate and the
      phospholipid used for the stabilization of the dispersions was also investigated
      by light microscopy. The nanoparticles usually display a bimodal crystallization
      event which depends on the thermal treatment and cannot be attributed to
      crystalline polymorphism. The ratio of the particle fractions crystallizing in
      the two successive steps strongly depends on the particle size of the
      dispersions. The presence of larger particles leads to an increased fraction
      crystallizing at higher temperature and a higher recrystallization tendency upon
      storage. The observed peculiarities of the crystallization behavior seem to be
      mainly caused by the presence of particles with different shapes (cylindrical and
      spherical) as observed in electron microscopy. Alterations in the composition of
      the nanoparticles may also play a role.

PMID- 15990284
TI  - Synthesis and biological evaluation of new N-substituted-N'-(3,5-di/1,3,5
      trimethylpyrazole-4-yl)thiourea/urea derivatives.
AB  - Several thiourea and urea derivatives were prepared by the reaction of 4
      aminopyrazoles with substituted isothiocyanates or isocyanates. The novel
      compounds were tested anticonvulsant activity using by pentylenetetrazole-induced
      seizure (PTZ) and maximal electroshock seizure (MES) tests. Among the tested
      compounds, thiourea derivatives of 4b were afforded 90 and 100% protection in PTZ
      and MES tests at 50mg/kg, respectively. Urea derivatives of 5a and 5b were
      afforded 82 and 100% protection both at 25 and 50mg/kg. Also synthesized
      compounds were screened for antituberculosis activity against Mycobacterium
      tuberculosis H37Rv at 6.25 microg/mL concentration but they were not found active
      at these concentration. In addition, some selected compounds were evaluated for
      in vitro anti-HIV activity and they were all negative.

PMID- 15990285
TI  - Campylobacter jejuni isolated from retail poultry meat, bovine feces and bile,
      and human diarrheal samples in Japan: comparison of serotypes and genotypes.
AB  - To determine the significance of poultry and bovine as infectious sources of
      Campylobacter jejuni in Japan, the serotype distribution and pulsed-field gel
      electrophoresis (PFGE) patterns of poultry and bovine isolates were compared with
      those of isolates from patients with diarrhea in Akita (Japan). Serotypes O:2 and
      O:4-complex were common in human, poultry, and bovine isolates, and serotype
      O:23,36,53 was common in human and bovine isolates. SmaI PFGE patterns of
      isolates belonging to these serotypes were generated. Eight PFGE patterns were
      shared by poultry and human isolates and three patterns were shared by human and
      bovine isolates. Further analysis of the isolates having the same SmaI PFGE
      pattern by KpnI PFGE confirmed that four patterns and two patterns were still
      shared by poultry and human isolates, and bovine and human isolates,
      respectively. Thus, serotypic and genotypic data indicated a possible link
      between sporadic human campylobacteriosis and C. jejuni from retail poultry and
      bovine bile and feces, suggesting that bovine serves as an infectious source of
      C. jejuni in Japan, as is observed in other countries.

PMID- 15990286
TI  - Recurrence of pulmonary intravascular bronchoalveolar tumor with mediastinal
      metastasis 20 years later.
AB  - Pulmonary intravascular bronchoalveolar tumor (IVBAT) also recognized as
      pulmonary epithelioid hemangioendothelioma, is a rare malignant vascular tumor of
      unknown etiology. IVBAT is a tumor of multicentric origin and the lungs are
      rarely involved, with only about 60 cases of pulmonary IVBAT described in the
      literature. The prognosis is unpredictable, with life expectancy ranging from 1
      to 15 years. We report an unusual case of pulmonary IVBAT that recurred in the
      lung with metastasis to the mediastinum.

PMID- 15990287
TI  - Development of nanostructured biomedical micro-drug testing device based on in
      situ cellular activity monitoring.
AB  - Integration of micro and nanofabrication techniques with biotechnology has
      resulted in the development of in vitro analytical and diagnostic tools for
      biomedical applications. The focus of such technology has primarily been on
      therapeutic and sensing applications. The long-term integration of cells with
      inorganic materials provides the basis for novel sensing platforms. This paper
      describes the creation of, nanoporous, biocompatible, alumina membranes as a
      platform for incorporation into a cell based device targeted for in situ
      recording of cellular electrical activity variations due to the changes
      associated with the surrounding microenvironments more specifically due to the
      effect of therapeutic drugs. Studies described herein focus on the interaction of
      nanoporous alumina substrates embedded in silicon, patterned with cells of
      interest. The cells that have been used to develop the in vitro test platform are
      primary hippocampal neurons. Demonstrated here, is the fidelity of such a system
      in terms of determination of cell viability, proliferation, and functionality.
      The response of the cells to the "drug" molecules is electro-optically
      characterized in an in situ manner. The capability of such, micro fabricated
      nanoporous membranes as in vitro drug testing platforms, is first theoretically
      estimated using two dimensional finite element modeling of the diffusion of the
      molecules of interest through the nanoporous substrate using CFDRC. It is then
      experimentally established, using glucose and immunoglobulin G (IgG).

PMID- 15990288
TI  - On-farm production of AM fungus inoculum in mixtures of compost and vermiculite.
AB  - On-farm production of arbuscular mycorrhizal (AM) fungus inoculum can reduce the
      cost of the inoculum and increase utilization of this symbiosis in plant
      production. Bahiagrass (Paspalum notatum Flugge) seedlings, colonized by AM
      fungi, were transplanted into raised bed enclosures. Media within the enclosures
      was vermiculite mixed with either field soil or yard clippings compost in
      Experiment I and vermiculite mixed with yard clippings compost or dairy
      manure/leaf compost in Experiment II. Compost and vermiculite mixtures yielded
      more propagules of AM fungi than soil-based mixtures in Experiment I. Growth of
      plants in a 1:4 (v/v) mixture of yard clippings compost and vermiculite produced
      more inoculum (503 propagules cm(-3)) than growth in 1:9 and 1:99 (v/v) mixtures
      (240 and 42 propagules cm(-3), respectively). Water, inorganic nutrient solution
      minus P, and fish protein digest were added to inoculum production enclosures in
      Experiment II. Results indicated that supplemental nutrient addition was
      unnecessary. This method produces a concentrated inoculum of AM fungi in a form
      readily used as an amendment to horticultural potting media for the production of
      vegetable seedlings.

PMID- 15990289
TI  - Effects of four different doses of organic manures in the production of
      Ceriodaphnia cornuta.
AB  - Mass culture of Ceriodaphnia cornuta was done by using a mixture of organic
      manures: cattle manure:poultry droppings:mustard oil cake (1:1:1) at four
      different doses: 0.263 kg/m3 (first dose), 0.526 kg/m3 (second dose), 1.052 kg/m3
      (third dose) and 2.104 kg/m3 (fourth dose). The peak of C. cornuta was found on
      10th day of inoculum in first two doses and on 14th and 18th day in third and
      fourth doses, respectively. Among these four doses, significantly (P<0.01) higher
      numbers of organisms (1930/l) were found in the fourth dose followed by third
      (1470/l), second (1017/l) and first (733/l) doses, respectively. The number of
      organisms decreased faster in two lower doses than higher doses. pH ranged from
      7.20 to 8.09, 7.46 to 8.01, 7.55 to 7.89 and 7.61 to 8.03 in first, second, third
      and fourth doses, respectively. Dissolved oxygen showed inverse relationship with
      the dose of manures applied and direct relationship with number of organisms.
      This study showed that 3.28-4.63 mg/l dissolved oxygen was optimum to obtain the
      bloom of C. cornuta under the present manure schedule. Maximum number of organism
      was found when unionized ammonia and phosphate levels ranged between 0.65-0.85
      mg/l and 0.42-0.98 mg/l, respectively. The fourth dose of organic manure is
      optimum for the culture of C. cornuta in outdoor condition and the bloom of the
      live food can be obtained within 18 days of inoculum.

PMID- 15990290
TI  - Optimization of the medium composition for production of mycelial biomass and exo
      polymer by Grifola frondosa GF9801 using response surface methodology.
AB  - In this work, a three-level Box-Behnken factorial design was employed combining
      with response surface methodology (RSM) to optimize the medium composition for
      the production of the mycelial biomass and exo-polymer in submerged cultures by
      Grifola frondosa GF9801. A mathematical model was then developed to show the
      effect of each medium composition and their interactions on the production of
      mycelial biomass and exo-polymer. The model estimated that, a maximal yield of
      mycelial biomass (17.61 g/l) could be obtained when the concentrations of
      glucose, KH2PO4, peptone were set at 45.2 g/l, 2.97 g/l, 6.58 g/l, respectively;
      while a maximal exo-polymer yield (1.326 g/l) could be achieved when setting
      concentrations of glucose, KH2PO4, peptone at 58.6 g/l, 4.06 g/l and 3.79 g/l,
      respectively. These predicted values were also verified by validation
      experiments. Compared with the values obtained by other runs in the experimental
      design, the optimized medium resulted in a significant increase in the yields of
      mycelial biomass and exo-polymer. Maximum mycelial biomass yield of 22.50 g/l was
      achieved in a 15-l fermenter using the optimized medium.

PMID- 15990291
TI  - Structural changes of plant residues during decomposition in a compost
      environment.
AB  - The degradation of plant material during composting was investigated
      qualitatively by scanning electron microscopy (SEM) and quantitatively by
      chemical methods. Decomposition of Miscanthus (Miscanthus oogiformis L.), hemp
      (Cannabis sativa L.) and wheat (Triticum aestivum L.) straw was observed by
      placing litterbags containing these materials in compost piles. Hemp and
      Miscanthus straw were more stable than wheat straw, but the two materials
      differed in the way they were degraded despite similar chemical compositions.
      Hemp straw was broken down in more flexible structures compared to the rigid
      breakdown of Miscanthus straw. It was concluded that the anatomical arrangement
      of the tissue is just as important as the content of recalcitrant compounds in
      determining decomposition rate. Thus, when using composted plant materials as
      growing medium, the choice of material must depend not only on nutritional
      quality but also on structural quality. This study indicated that hemp material
      might be a good structural component in a compost to be used as a growing medium.

PMID- 15990292
TI  - Thermophilic composting of food waste.
AB  - A laboratory reactor was designed to study the effects of operating parameters
      (air suction rate, seeding and agitation) on the composting process of a
      synthetic food waste made of dog food. Experimental results showed that the
      synthetic food waste could be composted within 4 days and the final compost
      passed the maturity tests. In most cases except those with 32% of seeding, the
      process involved two major stages of composting. The two peak temperatures
      between 50 and 60 degrees C occurred at 8-12th hour and 50-65th hour,
      respectively. Operating parameters that converted the most volatile solids and
      carbons in the feedstock were as follows: 1.6 l air/kg dry solid-min of air
      suction rate, 32% of seeding and 50% of agitation time.

PMID- 15990293
TI  - A prodrug system for hydroxylamines based on esterase catalysis.
AB  - The synthesis and reactivity of hydroxy hydroxamates as models for a prodrug form
      of hydroxylamine are described. Gamma-hydroxy hydroxamates were found to enable
      hydroxylamine release via lactonisation. Hydroxamates were found to undergo
      esterase catalysed hydrolysis.

PMID- 15990294
TI  - Molecular complexity from aromatics: synthesis and photoreaction of endo
      tricyclo[5.2.2.0(2,6)]undecane--a stereoselective route to tricyclic framework of
      protoilludanes.
AB  - A stereoselective route towards protoilludanoids from simple aromatic precursor
      is described. The methodology involves in situ generation of
      spiroepoxycyclohexadienone and cycloaddition with cyclopentadiene and
      photochemical 1,3-acyl shift.

PMID- 15990295
TI  - Modeling K(m) values using electrotopological state: substrates for cytochrome
      P450 3A4-mediated metabolism.
AB  - In order to determine K(m) values of substrates for CYP3A4-mediated metabolism,
      an in silico model has been developed in the present work. Using
      electrotopological state (E-state) indices, together with Bayesian-regularized
      neural network (BRNN), we have described an in silico method to model log(1/K(m))
      values of various substrates. The relative importance of the E-state indices is
      analyzed by principal component analysis. By using an additional external test
      set, which is independent of the training set, the robustness and predictivity of
      the model are also validated.

PMID- 15990296
TI  - Synthesis and structural modeling of the amphiphilic siderophore rhizobactin-1021
      and its analogs.
AB  - We describe two convenient syntheses of rhizobactin-1021 (Rz), a citrate-based
      siderophore amphiphile produced by the nitrogen-fixing root symbiont Rhizobium
      meliloti-1021, and several analogs. Our approach features a singly amidated, tert
      butyl-protected citrate intermediate that easily affords a variety of Rz analogs
      in the late stages of the synthesis. Structural modeling and the monolayer
      behavior of Rz and its metal complexes are consistent with a structural
      reorganization upon Rz-mediated iron chelation.

PMID- 15990297
TI  - Synthesis of an N-acyl sulfamate analog of luciferyl-AMP: a stable and potent
      inhibitor of firefly luciferase.
AB  - In the first of two half-reactions resulting in the emission of visible light,
      firefly luciferase forms luciferyl-adenylate from its natural substrates beetle
      luciferin and Mg-ATP. The acyl-adenylate is subsequently oxidized producing the
      light emitter oxyluciferin in an electronically excited state. In vitro, under
      mild conditions of temperature and pH, the acyl-adenylate intermediate is readily
      hydrolyzed and susceptible to oxidation. We report here the multi-step synthesis
      and physical and enzymatic characterization of an N-acyl sulfamate analog of
      luciferyl-adenylate, 5'-O-[(N-dehydroluciferyl)-sulfamoyl]-adenosine (compound
      5). This represents the first example of a stable and potent (Ki = 340 nM)
      reversible inhibitor of firefly luciferase activity based on the structure of the
      natural acyl-adenylate intermediate. Additionally, we present the results of
      limited proteolysis studies that demonstrate that the binding of the novel acyl
      adenylate analog protects luciferase from proteolysis. The findings presented
      here are interpreted in the context of the hypothesis that luciferase and the
      other enzymes in a large superfamily of adenylate-forming proteins adopt two
      conformations to catalyze two different partial reactions. We anticipate that the
      novel N-acyl sulfamate analog will be a valuable reagent in future studies
      designed to elucidate the role of conformational changes in firefly luciferase
      catalyzed bioluminescence.

PMID- 15990298
TI  - Synthesis, structure-activity relationships, and anxiolytic activity of 7-aryl
      6,7-dihydroimidazoimidazole corticotropin-releasing factor 1 receptor
      antagonists.
AB  - 7-Aryl-6,7-dihydroimidazoimidazoles represent a novel series of high-affinity
      corticotropin-releasing factor 1 receptor antagonists. Here, we report their
      synthesis and SAR as well as behavioral activity of two exemplary compounds, 7b
      and 7k, in a mouse canopy model of anxiety.

PMID- 15990299
TI  - Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. Part 3:
      Chemical derivatization.
AB  - GE23077 is a novel RNA polymerase inhibitor that is isolated from the
      fermentation broth of an Actinomadura sp. It is a cyclic heptapeptide complex
      made up of four factors, differing in the structure of acyl group connected to
      the side chain of an alpha,beta-diaminopropanoic acid moiety and in the
      configuration of the stereocenter of an alpha-amino-malonic acid residue.
      Although GE23077 shows strong inhibitory activity on both Rifampicin-sensitive
      and -resistant polymerases, it exhibits poor antimicrobial activity. The most
      reasonable explanation for this property has been based on the lack of
      penetration of the molecule across the bacterial membrane, owing to its strong
      hydrophilic character. To improve penetration, several parts of the molecule were
      accordingly modified with the aim of altering the physico-chemical properties of
      GE23077. The current SAR study has identified moieties important for RNA
      polymerase activity.

PMID- 15990300
TI  - The tert-butyl dimethyl silyl group as an enhancer of drug cytotoxicity against
      human tumor cells.
AB  - In this study, we synthesized a series of enantiomerically pure (2R,3S)
      disubstituted tetrahydropyranes with diverse functional groups using known
      methodologies. In addition to the tert-butyl dimethyl silyl group, other common
      protecting groups for hydroxyl groups such as allyl, acetate, and benzoate were
      used to obtain appropriate derivatives. Pure compounds were evaluated in vitro
      against HL60 human leukemia cells and MCF7 human breast cancer cells. From the
      growth inhibition data a structure-activity relationship was obtained. Overall
      the results point to the relevant role of the tert-butyl dimethyl silyl group in
      the modulation of cytotoxic activity.

PMID- 15990301
TI  - Novel antiglaucoma prodrugs and codrugs of ethacrynic acid.
AB  - The purpose of this study was to synthesize a novel prodrug of ethacrynic acid
      (ECA) with short chain polyethylene glycols (PEGs) and codrugs of ECA with the
      beta-adrenergic blocking agent atenolol (ATL) or timolol (TML) to overcome the
      adverse effects of ECA and to enhance its physicochemical properties.

PMID- 15990302
TI  - Discovery of a novel and potent series of dianilinopyrimidineurea and urea
      isostere inhibitors of VEGFR2 tyrosine kinase.
AB  - A series of dianilinopyrimidineureas demonstrate potency as VEGFR2 kinase
      inhibitors.

PMID- 15990303
TI  - Interaction of chiral MS-245 analogs at h5-HT6 receptors.
AB  - Optically active pyrrolidinylmethylindole analogs related in structure to the
      benzenesulfonyltryptamine 5-HT(6) receptor antagonist MS-245 were evaluated and
      their R-isomers were found to bind with affinity higher than their S-enantiomers.

PMID- 15990304
TI  - The molecular basis for coxib inhibition of p38alpha MAP kinase.
AB  - In this work, we present the results of two combined approaches, molecular
      docking and comparative molecular field analysis (CoMFA), to propose how the
      selective cyclooxygenase-2 inhibitor celecoxib could act as a p38 mitogen
      activated protein (MAP) kinase inhibitor. The docking analysis revealed why
      celecoxib has a less favorable binding energy (DeltaG= -12.4kcal/mol) than the
      selective p38 MAP kinase (p38 MAPK) inhibitor, SB203580 (DeltaG= -22.2kcal/mol).
      The CoMFA results revealed unfavorable steric effects that can be related to the
      predicted lower p38 MAP kinase inhibitory activity of celecoxib. Additionally,
      FlexX and CoMFA results also suggested that etoricoxib, another selective COX-2
      inhibitor, could inhibit p38 MAP kinase.

PMID- 15990305
TI  - Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV
      activity and remarkable inverse antiviral resistance profiles.
AB  - A novel series of tyrosine-derived HIV protease inhibitors was synthesized and
      evaluated for in vitro antiviral activity against wild-type virus and two
      protease inhibitor-resistant viruses. All of the compounds had wild-type
      antiviral activities that were similar to or greater than several currently
      marketed HIV protease inhibitors. In addition, a number of compounds in this
      series were more potent against the drug-resistant mutant viruses than they were
      against wild-type virus.

PMID- 15990306
TI  - BCUT descriptors to predicting affinity toward A3 adenosine receptors.
AB  - The BCUT descriptors have been applied to the study of the A(3) adenosine
      receptor agonist effect of 32 adenosine analogues. A model, able to describe more
      than 80% of the variance in the experimental activity was developed with the use
      of the above-mentioned approach. Four different approaches (topological, Galvez
      topological charges indexes, Randic molecular profiles, and geometrical
      descriptors) failed to give satisfactory models for this property with the same
      number of variables in the equation. Although statistically significant models
      were derived containing descriptors other than BCUT, the best fitted model was
      still found with these descriptors.

PMID- 15990307
TI  - Erysipelas of the upper extremity following locoregional therapy for breast
      cancer.
AB  - Cellulitis is a well-known complication of lymphedema of the lower extremities.
      Erysipelas of the upper extremity complicating breast cancer therapy has never
      been reported in the English-language literature. We describe seven breast cancer
      patients with erysipelas of the upper extremity. Five had a predisposing injury
      to the extremity. All patients responded very well to intravenous antibiotics
      without any sequelae. They had rapid resolution with typical desquamation. No
      long-term sequelae were seen except for mild increase of lymphedema. Erysipelas
      should be listed as a rare complication after locoregional therapy for breast
      cancer. Intravenous penicillin should be used as the initial therapy. Prevention
      of arm lymphedema and avoidance of any trauma to the arm are important
      prophylactic measures. Sentinel lymph node biopsy reduces the rate of axillary
      lymph node dissection and thus should reduce the incidence of lymphedema and
      erysipelas.

PMID- 15990308
TI  - Large mammary hamartoma of axillary supernumerary breast tissue.
AB  - Hamartoma is an uncommon breast tumor and it is extremely rare to find it in
      ectopic breast tissue. We report the first case, to our knowledge, of a large
      hamartoma axillary supernumerary breast tissue. This report describes the case of
      a 33-year-old Brazilian patient who detected a lump in her left axillary
      supernumerary breast tissue at the same time as she was diagnosed with systemic
      erythematous lupus and corticoid treatment was initiated. The lesion showed
      progressive growth, reaching considerable proportions within a year, and it was
      removed with good esthetic and functional results.

PMID- 15990309
TI  - Breast carcinoma bone metastasis first presenting to single middle phalanx.
AB  - Phalangeal bone metastasis is rare. Breast cancer is known to metastasise to bone
      but rarely to fingers. This case presents the first site of breast cancer
      metastasis found on a single proximal phalanx causing pain and affecting hand
      function. For surgical symptomatic treatment the patient had a ray resection.
      Post-operatively the patient was pain free with excellent hand function.

PMID- 15990310
TI  - Repeatability of lower extremity kinetics and kinematics for standardized and
      self-selected running speeds.
AB  - INTRODUCTION: The purpose of this study was to determine the effects of self
      selected versus standardized running speeds on within-day and between-day
      repeatability of lower extremity kinematics and kinetics for running gait.
      METHODS: Subjects (six female, six male, age 18-35) were recreational athletes
      with no lower extremity injuries. The following study variables were analyzed
      using the coefficient of variation (CV): the peak angles for knee internal
      rotation, external rotation, varus, valgus, flexion, and extension; peak angles
      for ankle dorsiflexion and plantar flexion; peak impact force and propulsive
      force; and peak anterior, posterior, medial, and lateral ground reaction forces
      (GRFs). Data for the entire stance phase were analyzed using the coefficient of
      multiple correlation (CMC) for the following variables: anterior-posterior,
      medial-lateral, and vertical GRF; the angles and angular velocities for knee
      internal-external rotation, valgus-varus, flexion-extension, and ankle
      dorsiflexion-plantar flexion. Each variable was analyzed using a 2 x 2 (speed x
      day) repeated measures ANOVA (alpha = 0.05). RESULTS: The within-day
      repeatability for all of the significantly different variables was greater than
      the between-day repeatability. For variables with a significant difference based
      on speed, the standardized running speed had greater repeatability. CONCLUSIONS:
      Within-day repeatability is generally greater than between-day repeatability.
      Running speed had little effect on the repeatability of any study variable.
      Having subjects run at a standardized speed may not be as important as previously
      thought.

PMID- 15990311
TI  - A functional foot type classification with cluster analysis based on plantar
      pressure distribution during jogging.
AB  - The purpose of this study was to establish a reference dataset for peak pressures
      and pressure-time integrals during jogging, to compare this reference dataset
      with existing walking data and to develop a foot type classification, all based
      on plantar pressure data obtained from 215 healthy young adults. The subjects ran
      at 3.3 m s(-1) over a 16.5 m long running track, with a built-in pressure
      platform mounted on top of a force platform. Peak pressures, regional impulses
      and relative regional impulses were measured. These variables were found to be
      reliable (all intra class correlation coefficients above 0.75) and, except for
      the heel areas, gender and asymmetry effects could be neglected. Highest peak
      pressures were found under the heel due to large impact forces during initial
      contact phase (ICP). In the forefoot, the highest peak pressure was found under
      the second metatarsal (64.2 +/- 21.1 N cm(-2)). Compared to walking data, overall
      higher peak pressures and impulses and difference in hallux loading were found
      during barefoot jogging. Four pressure loading patterns were identified using a K
      means cluster analysis, based on the relative regional impulses underneath the
      forefoot: medial M1 pattern, medial M2 pattern, central pattern and central
      lateral pattern. These four pressure loading patterns could help in the
      functional interpretation of the foot behaviour during the stance phase in slow
      running.

PMID- 15990312
TI  - Evolution and emergence of Bordetella in humans.
AB  - Two highly infectious bordetellae, Bordetella pertussis and B. parapertussis,
      have emerged in historical times as co-dominant in human populations. Both of
      these cause acute disease (whooping cough), whereas their progenitor, B.
      bronchiseptica, is of variable virulence in a wide variety of animals. The
      remarkably close phylogenetic relatedness of these three bordetellae and the two
      independent jumps to humans provide a unique opportunity to examine the evolution
      and genetics involved in the emergence of acute human pathogens. We hypothesize
      that the more virulent strains in humans reflects how acutely infectious
      pathogens might be favored in communities with large contact networks.
      Furthermore, we suggest that the differential expression of the various virulence
      factors by the two human pathogens can be explained by immune-mediated
      competition between the strains. The evolutionarily favored strategies of both of
      the human bordetellae result in immunizing infections and acute epidemics.

PMID- 15990313
TI  - Rate of blood loss over 48 hours following total knee replacement.
AB  - The purpose of this study was to determine the rate of blood loss after total
      knee arthroplasty and assess the efficacy of drains using autologous blood
      transfusion. A prospective study was undertaken of 100 consecutive patients
      undergoing routine total knee arthroplasty. The diagnosis was osteoarthritis in
      85% of patients and rheumatoid arthritis in 12% of cases. The rate of blood loss
      was recorded hourly for the first 12 h, 4 hourly for the subsequent 12 h and 6
      hourly for the following 24 h. Autologous blood was reinfused within 12 h of
      surgery according to the protocol. Eighty-four percent of the total blood
      drained, was collected in the first 12 h and 94% in the first 24 h. 69% of the
      total blood which was drained was reinfused. The mean preoperative haemoglobin
      was 13.18 gm/dl and 10.23 gm/dl on the 5th day. A mean volume of 70-80 ml of
      homologous blood was reinfused in addition to the autologous transfusion in 11 of
      the 100 cases. There were no cases of deep or superficial sepsis, nor any
      identifiable complications related to the autologous blood transfusion. This
      study suggests it is safe to remove the postoperative joint drain after the 12-h
      period.

PMID- 15990314
TI  - Synthesis, antiproliferative, and antiplatelet activities of oxime- and
      methyloxime-containing flavone and isoflavone derivatives.
AB  - Certain oxime- and methyloxime-containing flavone and isoflavone derivatives were
      synthesized and evaluated for their antiproliferative activity against three
      solid cancer cells, human cervical epithelioid carcinoma (HeLa), hepatocellular
      carcinoma (SKHep1), and oral squamous cell carcinoma (SAS), which are commonly
      seen in Asian countries, including Taiwan. Selective compounds were also
      evaluated in the full panel of 60 human tumor cell lines and their mean GI50
      values were obtained. The preliminary assays indicated flavone-6-yl derivatives
      are the most cytotoxic while isoflavone-7-yl derivatives are the best
      antiplatelet agents. Among them, (E)-6-(2-methoxyiminopropoxy)-2-phenyl-4H-1
      benzopyran-4-one (14), (Z)-6-(2-hydroxyimino-2-phenylethoxy)-2-phenyl-4H-1
      benzopyran-4-one (18a), and (Z)-6-[2-hydroxyimino-2-(4-methoxyphenyl)ethoxy]-2
      phenyl-4H-1-benzopyran-4-one (18c) are three of the best antiproliferative agents
      with GI50 values of 0.8, 0.7, and 0.8 microM, respectively, against the growth of
      SKHep1; 0.9, 0.8, and 1.0 microM, respectively, against the growth of HeLa cells.
      Compound 18c is not only the most cytotoxic with a mean GI50 value of 0.08 microM
      against the full panel of 60 human tumor cell lines but also the only flavone
      derivative that exhibited a GI50 value of less than 1 microM against the growth
      of SAS. Flow cytometric analyses revealed that growth inhibition by 18c was due
      to accumulation in G2/M phase arrest and followed by apoptosis.

PMID- 15990315
TI  - Ladder-shaped polyether compound, desulfated yessotoxin, interacts with membrane
      integral alpha-helix peptides.
AB  - Ladder-shaped polyether compounds, represented by brevetoxins, ciguatoxins,
      maitotoxin, and prymnesins, are thought to possess the high affinity to
      transmembrane proteins. As a model compound of ladder-shaped polyethers, we
      adopted desulfated yessotoxin (2) and examined its interaction with glycopholin
      A, a membrane protein known to form a dimer or oligomer. Desulfated yessotoxin
      turned out to interact with the alpha-helix so as to induce the dissociation of
      glycopholin oligomers when examined by SDS and PFO gel electrophoresis. The
      results provided the first evidence that ladder-shaped polyethers interact with
      transmembrane helix domains.

PMID- 15990316
TI  - Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure
      activity relationships of pyrimidine-5-carboxamide derivatives.
AB  - Spleen tyrosine kinase (Syk) is a non-receptor-type tyrosine kinase which
      mediates diverse responses in haematopoietic cells. Therefore, Syk is an
      attractive therapeutic target, and in a study of Syk inhibitors as potentially
      new therapeutic agents, we discovered the 4-anilinopyrimidine-5-carboxamides.
      Enzyme screening indicated that an aminoethylamino moiety at the 2-position of
      the pyrimidine ring was important for Syk inhibitory activity, and an
      investigation of the substituents at the 4-position revealed that an anilino
      moiety substituted at the meta position was preferred. These compounds showed
      high selectivity for Syk, compared to other kinases, such as ZAP-70, c-Src, and
      PKC, and exhibited good inhibitory activities against 5-HT release from RBL
      cells. Among them, compound 9a inhibited the passive cutaneous anaphylaxis
      reaction in mice, with an ID50 of 13 mg/kg following subcutaneous administration.
      These results suggest that our compounds are worthy of further evaluation as new
      anti-allergic agents.

PMID- 15990317
TI  - Calorimetric and computational study of enthalpy of formation of 3,6-dibutanoic
      1,2,4,5-tetroxane.
AB  - A thermochemical a rather simple experimental technique method, is used to
      determine the enthalpy of the formation of 3,6-dibutanoic-1,2,4,5-tetroxane. The
      study is complemented with suitable theoretical calculations at the semiempirical
      and ab initio levels. A particular satisfactory agreement between both ways is
      found for the ab initio calculation at the 6-311G basis set level. Some possible
      extensions of the present procedure are pointed out.

PMID- 15990318
TI  - QSAR study on thiazole and thiadiazole analogues as antagonists for the adenosine
      A1 and A3 receptors.
AB  - Thiazole and thiadiazole analogues have been recently proposed as a novel
      promising class of adenosine A1 and A3 receptor antagonists. When appropriately
      modified, they show selectivity toward A1 or A3 receptors, which results in a
      variety of therapeutic potentialities of these ligands. In this work, we carried
      out a QSAR study on thiazole and thiadiazole analogues as antagonists for
      adenosine A1 and A3 receptors. To develop reliable models, we focused attention
      on any possible pitfalls of each step of QSAR process and approached each stage
      following accurate procedures. Application of datasets by using CODESSA software
      led to QSAR equations based on three and four descriptors for the adenosine A1
      and A3 receptor ligands, respectively. The obtained models allowed us to
      understand the main structural features that strongly correlate with the target
      property.

PMID- 15990319
TI  - Terpene trilactones from Gingko biloba: from ancient times to the 21st century.
AB  - Ginkgolides were always close to my heart. I continue to be strongly attracted to
      Ginkgo biloba, the ginkgolides and bilobalide. Starting in 1963, I became
      fascinated by these molecules while working on their isolation and structure
      elucidation in Sendai. Presumably, due to the ginkgolide studies, I received an
      invitation to join the faculty at Columbia University. After almost three decades
      of not touching the ginkgolide project, we have unexpectedly resumed the studies,
      at this time because of their enigmatic biological effects. This account is a
      reflection on earlier studies, as well as an outline of our current work.

PMID- 15990320
TI  - Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA
      receptor antagonist.
AB  - Polyamines and polyamine toxins are biologically important molecules, having
      modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin
      433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic
      receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine
      receptors. Polyamine toxins are used for the characterization of subtypes of
      ionotropic glutamate receptors, the Ca2+-permeable AMPA and kainate receptors. A
      derivative of the native polyamine toxin, philanthotoxin-56 (PhTX-56), has
      recently been shown to be an exceptionally potent and selective antagonist of
      Ca2+-permeable AMPA receptors. PhTX-56 and its labeled derivatives are promising
      tools for structure-function studies of the ion channel of the AMPA receptor. We
      now describe the design and synthesis of 3H-, 13C-, and 15N-labeled derivatives
      of PhTX-56 for molecular level studies of AMPA receptors. [3H]PhTX-56 was
      prepared from a diiodo-precursor with high specific radioactivity, providing the
      first radiolabeled ligand binding to the pore-forming part of AMPA receptors. For
      advanced biological NMR studies, 13C and 15N-labeled PhTX-56 were synthesized
      using solid-phase synthesis. These analogs can provide detailed information on
      the ligand-receptor interaction. In conclusion, synthesis of labeled derivatives
      of PhTX-56 provides important tools for future studies of the pore-forming region
      of AMPA receptors.

PMID- 15990321
TI  - Grayanane diterpenoids from the leaves of Craiobiodendron yunnanense.
AB  - Ten new grayanane diterpenoids, craiobiotoxins I-VIII (1-8) and craiobiosides A
      (9) and B (10), and five known grayanane diterpenoids, grayanotoxin XVIII,
      lyoniol A, lyoniol B, pieristoxin H, and grayanoside B were isolated from the
      leaves of Craiobiodendron yunnanense (Ericaceae). The structures of 1-10 were
      elucidated by spectroscopic methods including various 2D NMR and X-ray crystal
      diffraction experiments. In biological testing of our isolates, craiobiotoxin III
      (3) and lyoniol B showed moderate antifeedant activity.

PMID- 15990322
TI  - Direct gamma-spectrometric measurement of the 226Ra 186.2keV line for detecting
      238U/226Ra disequilibrium in determining the environmental dose rate for the
      luminescence dating of sediments.
AB  - In the age determination of sediments according to the luminescence method, it is
      important to know whether there was secular equilibrium in the Th and U decay
      series during accumulation of the environmental radiation dose in geological
      times. This can be investigated via gamma-ray spectrometry, whereby--in the
      (238)U series--(214)Pb and (214)Bi are considered as the indicators for (226)Ra
      mobility, and (210)Pb as the indicator for (226)Rn-emanation. In the present
      work, the direct measurement of (226)Ra--which can give extra information on the
      interpretation of the radioactive equilibrium--is investigated as to its
      precision and accuracy. Since there is a serious spectral interference on its
      186.2keV gamma-line (by (235)U at 185.7keV), various correction procedures were
      outlined and their performance was checked via the analysis of (certified)
      reference materials, leading to the recommendation of a "method of choice".

PMID- 15990323
TI  - Towards a laser neutron driver.
AB  - During the last few years, important experimental investigations have been made
      concerning the possibility of induced nuclear fission of high-Z elements by
      electromagnetic interaction (photofission, electron fission, neutron fission).
      Fast ions, neutrons and fission fragments from such interactions can be used to
      pump a laser medium, to produce energy from the (232)Th-(233)U nuclear fission
      cycle. The main aim of the present work is to study a three-step process, in a
      relatively new experimental scheme, in order to improve the number of both
      neutrons and fast ions. In the proposed scheme, high-energy particles and photons
      are produced by high-intensity laser beam interaction with a solid or gas target,
      which are utilized later on to trigger the nuclear reactions for the production
      of (photo) neutrons. These neutrons can give rise to fission of (232)Th that
      leads through a cascade of decays to (233)U --a highly fissionable material. Such
      a process will enhance, by an important factor, the final neutron flux and the
      energetic fission fragments. The use of a high intensity pulsed laser beam will
      control the turn-on and turn-off of the nuclear reactions and allow one to ensure
      the security of the whole operation. Finally, the produced neutrons are used to
      accomplish a major population inversion in an appropriate gas medium for the last
      stage of amplification of a high-contrast ultra-short laser seed pulse.

PMID- 15990324
TI  - A facile synthesis of [(11)C]acetylene.
AB  - Acetylene is a versatile synthon organic chemistry. The complexity and difficulty
      of synthesis of [(11)C]acetylene has limited its use as a labeling intermediate
      for PET radiotracers. A new method for production of [(11)C]acetylene has been
      developed in our laboratory that simplifies the synthesis procedure allowing for
      easy automation and implementation. The technique is a modification of Madsen et
      al. (1981, Phys. Med. Biol. 26(5), 875) that utilized carbon dioxide ((11)C) and
      barium. First [(11/12)C]CO(2) was trapped at room temperature on barium within a
      quartz reaction tube, then heated to 900 degrees C under hydrogen flow to release
      [(11)C]acetylene. Hydrogen gas is apparently oxidized to form water vapor which
      reacts immediately with the formed carbide to liberate acetylene. Radiochemical
      yields of 31.4--75.4% and specific activities of 0.11-- 161 mCi/micromol have
      been obtained with radiochemical purities greater than 99%. This technique
      provides a new, efficient and very practical synthesis of [(11)C]acetylene that
      can be utilized as synthon for novel PET radiopharmaceuticals.

PMID- 15990325
TI  - The behavior of single crystals of NaCl: Ca2+, Mn2+ exposed to gamma rays.
AB  - The behavior of single crystals of NaCl: Ca(2+), Mn(2+) exposed to gamma rays was
      explored for its potential usage as a dosimeter. The study was focused to the
      effect of dose and dose rate. The crystals were analyzed using thermoluminescence
      (TL). The productions of irradiation defects in the solid were correlated with
      the glow curve. F-centers were measured as function of the dose. The bleaching of
      the F-centers produced a decrease of the peak of the glow curve. The results
      showed that the response is linear in an interval up to 60 Gy.

PMID- 15990326
TI  - Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2
      Huntington's disease transgenic mice.
AB  - Striatal degeneration in Huntington's disease (HD) is associated with increases
      in perikaryal calbindin immunolabeling in yet-surviving striatal projection
      neurons. Since similar increases have also been observed in surviving striatal
      projection neurons after intrastriatal injection of the excitotoxin quinolinic
      acid, the increased calbindin in HD striatum has been interpreted to suggest an
      excitotoxic process in HD. We used immunolabeling to assess if calbindin is
      elevated in striatal projection neurons of R6/2 HD transgenic mice. These mice
      bear exon 1 of the human huntingtin gene with 144 CAG repeats and show some of
      the neuropathological signs (e.g., neuronal intranuclear inclusions) and clinical
      traits (e.g., wasting prior to early death) of HD. We found an increased
      frequency of calbindin-immunoreactive neuronal perikarya in the striatum of 6-
      and 12-week-old R6/2 mice compared to wild-type controls. This increase was most
      notable in the normally calbindin-poor dorsolateral striatum. We found no
      significant changes in the total area of striatum occupied by the calbindin
      negative striosomes and no consistent changes in striatal calbindin mRNA. The
      increase in calbindin in R6/2 striatal neurons was thus limited to the matrix
      compartment, and it may be triggered by increased Ca2+ entry due to the
      demonstrated heightened NMDA sensitivity of these neurons. The data further
      support the similarity of R6/2 mice to HD, and are consistent with the occurrence
      of an excitotoxic process in striatum in both.

PMID- 15990327
TI  - They are not stealthy in the heart: embryonic stem cells trigger cell
      infiltration, humoral and T-lymphocyte-based host immune response.
AB  - OBJECTIVE: The in vivo immunogenicity of Embryonic Stem Cells is controversial.
      At present, there is only in vitro evidence of MHC I expression by this cell
      population but vivid speculation about their immune-privileged state. The
      immunology aspect of ESC transplantation deserves thorough investigation.
      METHODS: We injected mouse ESC (expressing Green Fluorescent Protein, GFP) into
      injured myocardium of syngeneic, allogeneic and SCID recipients. Furthermore, we
      monitored host response for up to 4 weeks post cell transfer. We determined local
      response (CD 3, CD 11c expression by host cells), MHC I expression by donor
      cells, MHC-II expression within and around the graft, humoral response of
      allogeneic hosts using Flow Cytometry and evaluated the hosts' cytokine response
      using stimulated spleenocytes by means of ELISPOT. Cell survival was estimated by
      morphometry, by calculating the area of the GFP+ graft over the area of
      infarction at multiple sections of the harvested heart. RESULTS: There was
      significant cellular infiltration into and around the graft consisting of T
      lymphocytes (CD3+) and dendritic cells (CD 11c). Infiltration was detectable at 1
      week and progressed through 4 weeks following cell transplantation. The humoral
      Ab response was moderate at 2 weeks but frank at 4 weeks. ELISPOT demonstrated a
      Th1 pathway of donor specific T-lymphocyte response with strong IFN-gamma and Il
      2 production (figure A). MHC I expression was significant within the graft and
      maximal in the allogeneic groups. CONCLUSIONS: An immune response against
      transplanted ESC was demonstrated and the future use of ESC will likely require
      the use of systemic immunosuppression.

PMID- 15990328
TI  - A cardiac paraganglioma presenting with atypical chest pain.
AB  - Primary cardiac tumours are rare. The majority are benign and 75% are atrial
      myxomas. One of the more unusual benign tumours affecting the heart is a cardiac
      paraganglioma. A 56-year male was presented with a 6-month history of vague, left
      sided chest pain, intermittent parathesia of the left arm and dyspnoea on
      bending. Echocardiography documented a large, highly vascular mass, attached to
      the intra-atrial septum. All investigations, haematological, biochemical,
      neuroendocrine tumour markers and urinary cathecholamine levels, were within
      normal limits. Macroscopically the tumour involved the whole of the atrial
      septum, roof of the left atrium and extended to surround the superior vena cava,
      excluding total resection. The feeding vessels were ligated in the hope of
      infarcting the remainder of the tumour. In over 2-years of follow-up, the patient
      remains clinically stable. To our knowledge this is the first reported case where
      vascular ligation has been used to control a cardiac paraganglioma.

PMID- 15990329
TI  - Perioperative chemotherapy for bladder cancer.
AB  - The presence of occult micrometastases at the time of radical cystectomy leads to
      both distant and local failure in patients with locally advanced transitional
      cell carcinoma of the bladder. Cisplatin-based chemotherapy produces responses in
      40-60% of patients with metastatic bladder cancer. Perioperative administration
      of chemotherapy in bladder cancer patients theoretically can impart the same
      survival benefits demonstrated in patients with breast, lung and colon cancer.
      Both neoadjuvant and adjuvant therapy have been evaluated in patients with
      locally advanced bladder cancer. Studies evaluating adjuvant chemotherapy have
      been limited by inadequate statistical power to detect meaningful clinical
      answers, as well as experimental arms utilizing inadequate chemotherapy. Two
      randomized clinical trials have demonstrated a survival benefit for neoadjvuant
      CMV (Cisplatin, Methotrexate, Vinblastine) or MVAC (methotrexate, vinblastine,
      adriamycin, cisplatin). The aggregate of available evidence suggests that
      neoadjuvant cisplatin-based combination chemotherapy should be considered a
      standard of care for patients with muscle-invasive/locally advanced operable
      bladder cancer. However, some physicians prefer to defer chemotherapy until after
      surgery, when pathologic stage is defined, as well as the risk of relapse. In
      patients who are either unfit for or refuse radical cystectomy, neoadjuvant
      chemotherapy with or without radiation can render bladder preservation possible
      in patients who attain pathologic major response.

PMID- 15990330
TI  - Adjuvant treatment of malignant melanoma: where are we?
AB  - To date, no standard adjuvant therapy have increased overall survival in patients
      with malignant melanoma (MM). The effect of interferon alpha as a single agent or
      in combination has been widely explored in clinical trials. Critical reading of
      the major international randomised trials showed that response to interferon
      (IFN) in terms of improvement of overall survival (OS) may not be strictly
      correlated with the used dosage and that duration of therapy may impact disease
      free survival (DFS) but not OS. Patients' heterogeneity could be an explanation
      for the discordant data of the international literature. Indeed, majority of
      these studies started in late 1980s or early 1990s, when accurate staging
      procedure were not available yet. The adequate surgical treatment should be
      considered as an independent variable in the analysis of MM adjuvant protocols.
      Considering the treatment cost, which is the main goal: DFS, OS or quality of
      life? Answering these questions is difficult, but some considerations must be
      taken to put order in this field. Putting together data from all different
      studies, IFN therapy seems to protect MM patients from recurrences during the
      entire treatment period and a prolonged IFN therapy seems to improve DFS. The
      only positive result on OS was demonstrated for high-dose IFN (HD-IFN) in a
      single study (presenting a relatively short follow-up median) and not confirmed
      in a subsequent study from the same authors. Considering that low-dose interferon
      (LD-IFN) is tolerated much better than HD-IFN (about 10% versus more than 70% of
      cases with grade 3-4 toxicity, respectively), a prolonged LD-IFN (more than 2
      years) may represent a reasonable opportunity for MM patients, also considering
      its advantageous cost-effectiveness. Conversely, considering the improvement of
      OS as the main target of MM adjuvant therapy, the "wait and watch" attitude
      remains the only approach to be pursued at present. It is a physician's choice.

PMID- 15990331
TI  - Critical review of PET-CT for radiotherapy planning in lung cancer.
AB  - In the last decade, FDG-PET scans have had a major impact on the treatment of
      patients with NSCLC. The benefits of staging PET scans are well established, with
      improved selection of patients for curative radiotherapy or aggressive chemo
      radiotherapy. The large body of literature correlating FDG-PET with nodal
      pathology in NSCLC makes it rational to use PET for designing mediastinal
      radiation fields. However, suboptimal image-fusion and a low spatial resolution
      for PET scans, makes use of PET for defining target volumes for primary tumours
      questionable. Data on the role of PET scans for radiotherapy planning for limited
      stage small-cell lung cancer is limited, although the incorporation of FDG-PET
      positive regions would appear to be reasonable.

PMID- 15990332
TI  - Novel fragmentation pathway for CID of (b(n) - 1 + Cat)+ ions from model, metal
      cationized peptides.
AB  - We report a new fragmentation pathway for the CID of (b3 - 1 + Cat)+ product ions
      derived from the model peptide AXAG, where X = beta-alanine, gamma-aminobutyric
      acid, epsilon-amino-n-caproic acid, or 4-aminomethylbenzoic acid. By changing the
      amino acid to the C-terminal side of the amino acid X, and incorporating 15N and
      13C labeled residues at the same position, we conclude that the dissociation
      pathway most likely leads to a metal cationized nitrile. With respect to the
      various amino acids at position X, the putative nitrile product becomes more
      prominent, relative to the conventional (a3 - 1 + Cat)+ species, in the order
      beta-alanine < gamma-aminobutyric acid < epsilon-aminocaproic acid < 4
      aminomethylbenzoic acid. The pathway is not observed for peptides with alpha
      amino acids at position X. The product ion is observed most prominently during
      the CID of Li+ and Na+ cationized peptides, only to a small extent for Ag+
      cationized peptides, and not at all from protonated analogues.

PMID- 15990333
TI  - Plasmacytoid dendritic cells--virus experts of innate immunity.
AB  - Plasmacytoid dendritic cells (pDC) have emerged as a principal subset of
      dendritic cells in both human and mouse. PDC morphology, surface markers, their
      migration in vivo and the ability to rapidly produce large amounts of type I
      interferons (IFN-alpha/beta) in response to toll like receptor (TLR) triggering
      sets them apart from other dendritic cell subsets. This review highlights the
      features that make pDC uniquely able to sense and respond to viral infection.

PMID- 15990334
TI  - Connecting the dots: revealing the interactions of lymphocyte development and
      homeostasis in the immunobiology of aging.

PMID- 15990335
TI  - Risk for coronary artery disease and morbid preeclampsia: a commentary.
AB  - PURPOSE: A predisposition to coronary artery disease (CAD) may put women at risk
      for preeclampsia. Morbid preeclampsia (early, severe, recurrent, and with
      neonatal morbidity) represents the subset of preeclampsia of greatest public
      health concern. METHODS: We review here the published links between preeclampsia
      and CAD. RESULTS: Many risk factors are common to both CAD and preeclampsia.
      These include obesity; elevated blood pressure; dyslipidemia; insulin resistance;
      and hyperglycemia, together termed "Syndrome X"; as well as endothelial
      dysfunction; hyperuricemia; hyperhomocysteinemia; and abnormalities of
      inflammation, thrombosis, and angiogenesis. After pregnancy, women with
      preeclampsia are more likely to experience later life CAD. CONCLUSIONS: Both the
      association between CAD risk factors and preeclampsia and the association between
      preeclampsia and later CAD appears to be more pronounced among the subset of
      women with morbid preeclampsia. Thus, women at elevated risk for CAD may be at
      particularly high risk for morbid preeclampsia and women with morbid preeclampsia
      may be those at highest risk for later life CAD.

PMID- 15990336
TI  - A case-control study on the effect of exposure to different substances on the
      development of COPD.
AB  - PURPOSE: The purpose of this study was to examine the effect of exposure to
      different substances on the development of chronic obstructive pulmonary disease
      (COPD). METHODS: The case group consisted of 74 housewives. These were female
      patients who never smoked who had a diagnosis of COPD and were seen at the
      Cumhuriyet University Hospital in Sivas, Turkey, between January 1, 2001, and
      March 31, 2002. The control group consisted of 74 housewives; this group
      consisted of healthy women who never smoked who came to the hospital as visitors
      and who did not have the diagnosis of COPD. The control group was chosen by group
      matching of the age distribution of the women in the case group and the regions
      and the neighborhoods where they lived. All of the women in the case and control
      groups were evaluated with a questionnaire for exposure to wood ashes, biomass,
      and cigarette smoke in closed areas. RESULTS: No difference was found in the
      groups for exposure to wood ashes (p > 0.05). Logistic regression analysis
      resulted in the following odds ratio of COPD estimate for women with > or = 30
      years biomass exposure, 6.61 (95% Confidence interval [CI]: 2.17-20.18); for
      women with > or = 30 years cigarette smoke exposure, 4.96 (95% CI: 1.65-14.86).
      CONCLUSION: A statistically significant correlation was found between the effect
      of > or = 30 years of exposure to biomass and cigarette smoke exposure and the
      development of COPD.

PMID- 15990337
TI  - A simple nonparametric statistical thresholding for MEG spatial-filter source
      reconstruction images.
AB  - This paper proposes a simple statistical method for extracting target source
      activities from spatio-temporal source activities reconstructed from MEG
      measurements. The method requires measurements in a control condition, which
      contains only non-target source activities. The method derives, at each pixel
      location, an empirical probability distribution of the non-target source activity
      using the time course reconstruction obtained from the control period. The
      statistical threshold that can extract the target source activities is derived
      from the empirical distributions obtained from all pixel locations. Here, the
      multiple comparison problem is addressed with a two-step procedure involving
      standardizing these empirical distributions and deriving an empirical
      distribution of the maximum pseudo T value at each pixel location. The results of
      applying the proposed method to auditory-evoked measurements are presented to
      demonstrate the method's effectiveness.

PMID- 15990338
TI  - Cortical intercorrelations of frontal area volumes in schizophrenia.
AB  - BACKGROUND: Abnormal regional volume intercorrelations between selected cortical
      areas in schizophrenia patients were previously reported in several MRI studies.
      METHODS: A detailed analysis of frontal gray and white matter volume correlations
      with Brodmann's area volumes in the rest of the cortex was undertaken in normal
      subjects (n = 42) and patients with schizophrenia (n = 106), divided into good
      outcome (n = 52) and poor-outcome (Kraepelinian; n = 54) subtypes. RESULTS:
      Frontal gray matter volumes were correlated with temporal lobe volumes in
      schizophrenics but not in normal subjects. Some frontal-parietal and frontal
      occipital correlations showed a similar pattern. In comparison to normal
      subjects, schizophrenia patients showed weaker or absent intercorrelations
      intrafrontally, specifically between left motor-premotor and eye-movement areas
      (4, 6, 8) and dorsolateral area 44, as well as between left areas 9 and 46 vs.
      area 24 (cingulate gyrus). Poor outcome among patients with schizophrenia was
      associated with weaker correlations between left frontal area 9 and both medial
      and lateral temporal cortices, as compared to normal subjects or good-outcome
      patients. CONCLUSIONS: There appears to be a structural component in the task or
      symptom-related dysfunctional interactions between the frontal and more posterior
      cortical regions with preferential pathological involvement of frontotemporal and
      more limited involvement of frontoparietal and fronto-occipital systems in
      schizophrenia. Impaired regional associations within the frontal lobe, between
      left motor-premotor and Broca's areas, may play a role in language processing
      deficits in schizophrenia, while frontocingulate disconnection may result in
      working memory disturbances. Poor outcome may be associated with more widespread
      disconnections between prefrontal vs. cingulate and temporal regions in the left
      hemisphere, consistent with a disruption along the course of the left cingulum or
      uncinate bundles.

PMID- 15990339
TI  - Atlas-based hippocampus segmentation in Alzheimer's disease and mild cognitive
      impairment.
AB  - This study assesses the performance of public-domain automated methodologies for
      MRI-based segmentation of the hippocampus in elderly subjects with Alzheimer's
      disease (AD) and mild cognitive impairment (MCI). Structural MR images of 54 age-
      and gender-matched healthy elderly individuals, subjects with probable AD, and
      subjects with MCI were collected at the University of Pittsburgh Alzheimer's
      Disease Research Center. Hippocampi in subject images were automatically
      segmented by using AIR, SPM, FLIRT, and the fully deformable method of Chen to
      align the images to the Harvard atlas, MNI atlas, and randomly selected, manually
      labeled subject images ("cohort atlases"). Mixed-effects statistical models
      analyzed the effects of side of the brain, disease state, registration method,
      choice of atlas, and manual tracing protocol on the spatial overlap between
      automated segmentations and expert manual segmentations. Registration methods
      that produced higher degrees of geometric deformation produced automated
      segmentations with higher agreement with manual segmentations. Side of the brain,
      presence of AD, choice of reference image, and manual tracing protocol were also
      significant factors contributing to automated segmentation performance. Fully
      automated techniques can be competitive with human raters on this difficult
      segmentation task, but a rigorous statistical analysis shows that a variety of
      methodological factors must be carefully considered to insure that automated
      methods perform well in practice. The use of fully deformable registration
      methods, cohort atlases, and user-defined manual tracings are recommended for
      highest performance in fully automated hippocampus segmentation.

PMID- 15990340
TI  - Molecular phylogenetics and biogeography of Lepus in Eastern Asia based on
      mitochondrial DNA sequences.
AB  - In spite of several classification attempts among taxa of the genus Lepus,
      phylogenetic relationships still remain poorly understood. Here, we present
      molecular genetic evidence that may resolve some of the current incongruities in
      the phylogeny of the leporids. The complete mitochondrial cytb, 12S genes, and
      parts of ND4 and control region fragments were sequenced to examine phylogenetic
      relationships among Chinese hare taxa and other leporids throughout the World
      using maximum parsimony, maximum likelihood, and Bayesian phylogenetic
      reconstruction approaches. Using reconstructed phylogenies, we observed that the
      Chinese hare is not a single monophyletic group as originally thought. Instead,
      the data infers that the genus Lepus is monophyletic with three unique species
      groups: North American, Eurasian, and African. Ancestral area analysis indicated
      that ancestral Lepus arose in North America and then dispersed into Eurasia via
      the Bering Land Bridge eventually extending to Africa. Brooks Parsimony analysis
      showed that dispersal events followed by subsequent speciation have occurred in
      other geographic areas as well and resulted in the rapid radiation and speciation
      of Lepus. A Bayesian relaxed molecular clock approach based on the continuous
      autocorrelation of evolutionary rates along branches estimated the divergence
      time between the three major groups within Lepus. The genus appears to have
      arisen approximately 10.76 MYA (+/-0.86 MYA), with most speciation events
      occurring during the Pliocene epoch (5.65+/-1.15 MYA approximately 1.12 +/- 0.47
      MYA).

PMID- 15990341
TI  - The genus Cyphophthalmus (Arachnida, Opiliones, Cyphophthalmi) in Europe: a
      phylogenetic approach to Balkan Peninsula biogeography.
AB  - In this study, we present phylogenetic data to characterize the relationships
      among sironids centered in the Balkan region, and use these results to discuss
      biogeographical aspects of sironid evolution. Analysis of ca. 4.5 kb of sequence
      data from three nuclear and two mitochondrial genes reveals monophyly of a Balkan
      clade for which we resurrect the name Cyphophthalmus, considered a junior synonym
      of Siro for over a century. This clade diversified into several groups, and at
      least three of them--the duricorius group, the serbicus group, and the minutus
      group--are well corroborated by the data as monophyletic lineages. The members of
      the different groups, mostly living in troglobitic environments, have diversified
      in overlapping geographic regions, with evidence of an eastern origin for the
      group. Our data also suggest that mitochondrial and nuclear genes are all
      contributing towards the final resolution of the combined analysis of the data.

PMID- 15990342
TI  - Mature dendritic cells secrete exosomes with strong ability to induce antigen
      specific effector immune responses.
AB  - Exosomes are secreted vesicles formed in late endocytic compartments. Immature
      dendritic cells (DCs) secrete exosomes which transfer functional MHC-peptide
      complexes to other DCs. Since immature and mature DCs induce different functional
      T cell responses (i.e., tolerance versus priming), we asked whether DC maturation
      also influenced the priming abilities of their exosomes. We show that immature
      and mature murine DCs secrete morphologically similar exosomes. Extensive
      proteomic analysis of the two exosome populations showed identical overall
      protein composition, and provided an exhaustive image of the protein composition
      of DC-derived exosomes. By quantitative analysis, however, exosomes from mature
      DCs proved enriched in MHC class II, B7.2, ICAM-1, and depleted in MFG-E8, as
      compared to immature exosomes. In functional T cell stimulation assays, exosomes
      secreted by mature DCs were 50- to 100-fold more potent than exosomes from
      immature DCs, both in vitro and in vivo. MHC class II and ICAM-1 were necessary
      for the increased immune activity of exosomes secreted by mature DCs. Therefore,
      changes in protein composition and priming abilities of exosomes reflect the
      maturation signals received by DCs.

PMID- 15990343
TI  - Solvent-localized NMR spectroscopy using the distant dipolar field: a method for
      NMR separations with a single gradient.
AB  - Solvent-localized NMR (SOLO) is a new method which allows the separation of NMR
      spectra of substances dissolved in different solvents. It uses the selective
      HOMOGENIZED pulse sequence to produce a two-dimensional NMR spectrum resulting
      from intermolecular zero-quantum coherences in one distinct solvent. The detected
      signal is locally refocused by the action of the distant dipolar field, which is
      created by a frequency selective pulse only in regions containing the selected
      solvent. The prerequisites are that the different solvents have sufficiently
      different chemical shifts to be excited separately and that compartments with
      different solvents are spatially separated by more than the typical diffusion
      distance. Here, the method is demonstrated for the solvents water and DMSO on a
      length scale of 0.5 mm. Because signal in the spectra is refocused locally, SOLO
      is insensitive to variations in the magnetic field which may result from
      inhomogeneities or structures in the sample. This makes applications in strongly
      structured samples possible. SOLO is the first method that achieves localization
      of NMR signal with a single gradient pulse. Therefore, it can be used in
      conventional NMR spectrometers with one-axis gradient systems and lends itself to
      a wide range of applications including in vivo NMR.

PMID- 15990344
TI  - Efficient determination of low-frequency normal modes of large protein structures
      by cluster-NMA.
AB  - The structure-function relationship is critical to understanding the biologically
      relevant functions of protein structures. Various experimental techniques and
      numerical modeling methods, normal mode analysis (NMA) in particular, have been
      employed to gain insight into this relationship. Experimental methods are often
      unable to provide all the desired information and comprehensive modeling
      techniques are often too computationally expensive. The authors build upon and
      optimize their cluster normal mode analysis (cNMA) tool, which uses embedded
      rigid-bodies and harmonic potentials to capture the biologically significant, low
      frequency, oscillations of protein structures. cNMA represents atomic details
      with a scalable number of degrees-of-freedom, which can be chosen independent of
      structure size. This representation overcomes the otherwise quadratic order
      memory requirements and cubic order computational complexity associated with
      traditional all-atom NMA. cNMA is two orders of magnitude faster than traditional
      all-atom NMA when clustering by residue (very high resolution) and in the more
      traditional application using a fixed number of clusters, cNMA computationally
      scales as O(n), which is two orders of complexity faster than all-atom NMA. cNMA
      is presented and very large example structures with up to 10(6) atoms are
      analyzed on a notebook PC in the time scale of minutes/hours. The resulting mode
      shapes help identify biologically significant, conformational pathways.

PMID- 15990345
TI  - Inhalation method determines outcome of capsaicin inhalation in patients with
      chronic cough due to sensory hyperreactivity.
AB  - BACKGROUND: For patients with idiopathic chronic cough, a subgroup is recognised
      with respiratory symptoms induced by scents and chemicals. The diagnosis of
      sensory hyperreactivity (SHR) has been suggested for this group of patients and
      can be made using a capsaicin inhalation test. The aim of the present study was
      to compare the results of inhaling capsaicin by tidal breathing with those
      obtained by the dosimeter method regarding repeatability, agreement, and ability
      to distinguish patients with SHR from healthy controls. METHODS: A total of 15
      patients with chronic cough due to SHR and 15 healthy control subjects underwent
      a randomised cross-over protocol and were provoked in a double-blind, randomised
      fashion with vehicle and two concentrations of inhaled capsaicin, using either
      the tidal breathing or dosimeter method, in a total of four challenges
      opportunities, two with each method. RESULTS: Patients coughed more and showed
      more respiratory symptoms than healthy controls with each dose of capsaicin.
      Compared with tidal breathing, inhalation of capsaicin with the dosimeter method
      caused a significantly greater number of coughs and respiratory symptoms in both
      patients and controls. Among the patients, the mean number of coughs after
      inhalation of 1 mL of capsaicin 0.4 micromol/L from the first provocation with
      tidal breathing was 12 (95% CI: 7; 17) and after inhalation from the first
      provocation with the dosimeter method 32 (95% CI: 19; 46) (P < 0.05). Both
      methods showed good repeatability and similar ability to distinguish patients
      with SHR from healthy control subjects. CONCLUSIONS: For patients with SHR,
      capsaicin cough sensitivity is increased and repeatable. The dosimeter method
      caused more coughs and other respiratory symptoms than the tidal breathing
      method, indicating that the methods cannot be used interchangeably. Knowledge of
      the type of inhalation device used, the particle size, the airflow rate and the
      inspiratory flow rate are essential when comparing different studies of capsaicin
      induced cough.

PMID- 15990346
TI  - Pacific oyster hemocytes undergo apoptosis following cell-adhesion mediated by
      integrin-like molecules.
AB  - Previously, we demonstrated that in the Pacific oyster (Crassostrea gigas, a
      bivalve mollusc) apoptosis could be induced in hemocytes by treatment with Arg
      Gly-Asp (RGD) peptides which are known to function as an integrin ligand.
      However, it is unclear where the RGD peptides are binding to the C. gigas
      hemocytes, or what mechanism or molecules are involved, e.g., integrin-ligand
      interactions. Therefore, this study was undertaken to investigate the binding
      interactions in C. gigas hemocytes. Initially, to confirm the presence of RGD
      recognizing integrin-like molecule(s) on the hemocytes, we assessed the
      enhancement of spreading ability, and found that spreading ability was enhanced
      by immobilized human fibronectin, a fibronectin fragment containing the RGD
      motif, and C. gigas plasma in the presence of divalent cations. Interestingly,
      viability of the spreading hemocytes dramatically decreased 24 h later and DNA
      fragmentation with oligonucleosomal laddering of 180-200 bp in length was
      detected in the dead hemocytes by electrophoresis and TUNEL assay. These results
      indicated that hemocyte adhesion mediated by integrin-like molecules triggered
      apoptosis and suggested that integrin-activation contributes to the induction of
      apoptosis. This is the first report showing the possibility of an integrin
      functioning in the induction of apoptosis in invertebrate hemocytes.

PMID- 15990347
TI  - Characterization of calpastatin gene in fish: its potential role in muscle growth
      and fillet quality.
AB  - Calpastatin (CAST), the specific inhibitor of the calpain proteases, plays a role
      in muscle growth and meat quality. In rainbow trout (RBT), we identified cDNAs
      coding for two CAST isoforms, a long (CAST-L) and a short isoform (CAST-S),
      apparently derived from two different genes. Zebrafish and pufferfish CAST cDNA
      and genomic sequences were retrieved from GenBank and their exon/intron
      structures were characterized. Fish CASTs are novel in that they have fewer
      repetitive inhibitory domains as compared to their mammalian counterparts (one or
      two vs. four). The expressions of CAST mRNAs were measured in three RBT strains
      with different growth rates and fillet firmness that were fed either high energy
      or control diets. CAST-L and S expressions were significantly lower (p<0.01) in
      the strain that has the slowest growth rate and yielded the softest fillet.
      Strain or diet did not affect level of calpain mRNAs. However, the decrease in
      the CAST/calpain ratio at the mRNA level did not lead to a corresponding change
      in the calpain catalytic activity. Further investigation should reveal a
      potential use of the CAST gene as a tool to monitor fish muscle growth and fillet
      firmness.

PMID- 15990348
TI  - Analysis of unfolded protein response during single-chain antibody expression in
      Saccaromyces cerevisiae reveals different roles for BiP and PDI in folding.
AB  - The production of recombinant proteins is a critical technology for biotechnology
      and biomedical research. Heterologous expression of secreted proteins can
      saturate the cell's capacity to properly fold protein, initiating the unfolded
      protein response (UPR), and resulting in a loss of protein expression. The
      overexpression of chaperone binding protein (BiP) and disulfide bond isomerase
      (PDI) in Saccaromyces cerevisiae can effectively increase protein production
      levels of single-chain antibody (scFv) 4-4-20. These studies show that
      overexpression of BiP did not reduce the UPR activated by heterologous protein
      expression; however, overexpression of PDI or co-overexpression of BiP and PDI
      could reduce the UPR. We observed that co-overexpression of BiP and PDI led to
      the greatest secretion of scFv from the cell, but BiP and PDI appear to interact
      with the newly synthesized scFv at different stages in the folding process, as
      determined by pulse-chase analysis. We propose that BiP acts primarily to
      facilitate translocation and retain unfolded or partially folded scFv, and PDI
      actively folds the scFv through its functions as a catalyst, and/or an isomerase,
      of disulfide bonds. Free BiP is released when scFv is folded, stabilizing Ire1p,
      and leading to the reduced UPR.

PMID- 15990349
TI  - Functional analysis of four naturally occurring variants of human constitutive
      androstane receptor.
AB  - The human constitutive androstane receptor (CAR, NR1I3) is a member of the orphan
      nuclear receptor superfamily that plays an important role in the control of drug
      metabolism and disposition. In this study, we sequenced all the coding exons of
      the NR1I3 gene for 334 Japanese subjects. We identified three novel single
      nucleotide polymorphisms (SNPs) that induce non-synonymous alterations of amino
      acids (His246Arg, Leu308Pro, and Asn323Ser) residing in the ligand-binding domain
      of CAR, in addition to the Val133Gly variant, which was another CAR variant
      identified in our previous study. We performed functional analysis of these four
      naturally occurring CAR variants in COS-7 cells using a CYP3A4 promoter/enhancer
      reporter gene that includes the CAR responsive elements. The His246Arg variant
      caused marked reductions in both transactivation of the reporter gene and in the
      response to 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4
      dichlorobenzyl)oxime (CITCO), which is a human CAR-specific agonist. The
      transactivation ability of the Leu308Pro variant was also significantly
      decreased, but its responsiveness to CITCO was not abrogated. The transactivation
      ability and CITCO response of the Val133Gly and Asn323Ser variants did not change
      as compared to the wild-type CAR. These data suggest that the His246Arg and
      Leu308Pro variants, especially His246Arg, may influence the expression of drug
      metabolizing enzymes and transporters that are transactivated by CAR.

PMID- 15990350
TI  - Monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystals,
      inflammation, and cellular signaling.
AB  - Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals are
      responsible for acute synovial inflammation but also contribute to cartilage
      degradation and bone lesions within the joint. They activate multiple signal
      transduction pathways leading to cell activation and recruitment. Some signalling
      pathways are activated by both types of crystals, and other pathways may only be
      activated by one type depending on cell type, namely neutrophils, monocytes,
      macrophages, synovial fibroblasts, endothelial cells and chondrocytes. Cascades
      of activated proteins involve cytoplasmic membrane related proteins (FAK complex,
      Src family tyrosine kinases), but also MAPK and NF-kB pathways, leading to NO,
      prostanoid and cytokine production, and protease activation. This review will
      also focus on potential therapeutic targets related to cellular signalling in MSU
      and CPPD crystal-induced inflammation.

PMID- 15990351
TI  - Whole-genome amplification: relative efficiencies of the current methods.
AB  - Whole genome amplification (WGA) has emerged as a fundamental method for DNA
      analysis from limited quantities of genomic DNA in forensic analysis and disease
      gene discovery. Several strategies for WGA have been developed during the past
      decade, each with variable fidelity, yield and coverage of the amplified genome.
      In the search for a reliable and robust WGA method for genotyping short tandem
      repeat (STR) loci and single nucleotide polymorphic (SNP) markers, we initially
      tested four common methods, viz., degenerate oligonucleotide primed PCR (DOP),
      primer extension preamplification (PEP), improved-PEP (I-PEP) and multiple
      displacement amplification (MDA), typing the 13 CODIS tetranucleotide repeat
      loci. The results showed among all methods, I-PEP and MDA have higher genomic
      coverage. DOP and PEP produced locus and allelic dropouts. Therefore, we
      emphasized on the evaluation of I-PEP and MDA protocols, which shows that the two
      methods have their relative strengths and weaknesses. In general, the product
      yield of MDA is higher than that of I-PEP. However, the specificity of the I-PEP
      products appears to be higher, particularly in the analysis of STR loci. In the
      analysis of SNP markers, some loci amplify better using products obtained from I
      PEP whereas some worked better with MDA. Our analyses also demonstrate that blood
      spots on FTA cards are a more efficient source of DNA for I-PEP as compared to
      MDA, especially for STR analysis.

PMID- 15990352
TI  - Ultrasonic intensification of ozone and electrochemical destruction of 1,3
      dinitrobenzene and 2,4-dinitrotoluene.
AB  - The removal of nitroaromatics from polluted water is difficult due to their high
      stability to conventional treatment methods. This paper presents a method for the
      destruction of 1,3-dinitrobenzene and 2,4-dinitrotoluene in aqueous solutions.
      The compounds are shown to be stable to reaction with ozone, even under
      ultrasonic activation. The use of ultrasound enhances the rate of electrochemical
      reduction but the overall rate of reaction is still slow. However, the
      simultaneous application of ultrasound and ozonation to the electrochemical
      reaction allows virtually complete destruction of the compounds in short times.
      The effect is attributed to the ultrasonic enhancement of the electrochemical
      process giving intermediates that are susceptible to ozone oxidation. While
      further analytical work is needed to deduce the exact contributions of the
      various possible degradation mechanisms, the work demonstrates the synergies that
      can be gained by using combined techniques for the destruction of these difficult
      compounds.

PMID- 15990353
TI  - Interaction of chemokines and glycosaminoglycans: a new twist in the regulation
      of chemokine function with opportunities for therapeutic intervention.
AB  - Despite their key role in inflammation, the apparent redundancy in the chemokine
      system is often cited as an argument against probing chemokines as therapeutic
      targets for inflammation. However, this in vitro redundancy frequently does not
      translate to the in vivo situation, as exemplified by the use of specific
      receptor antagonists, ligand neutralizing or receptor blocking antibodies and
      gene-deleted mice in models of human disease. Specificity may be conferred onto
      the chemokine system by fine-tuning of responses both temporally and spatially
      through their highly specific interactions with glycosaminoglycans (GAGs). In
      this survey, we present evidence for specificity in the interaction and introduce
      emerging technologies that enable detailed assessment of protein-GAG
      interactions. Finally, we address the issue of exploitation of this interaction
      for therapeutic advantage.

PMID- 15990354
TI  - Genomics: success or failure to deliver drug targets?
AB  - For decades, the entire pharmaceutical industry has focused on a limited number
      of drug targets. Owing to advances in molecular biology and genome technology at
      the beginning of the 1990s, discovery and isolation of a large number of genes
      from the human genome became feasible. This triggered a multi billion US dollars
      investment by both biotechnology and pharmaceutical companies to gain access to
      and patent as many potential drug targets as possible. Although the combined
      effort of publicly funded projects and private investments resulted in rapid
      identification of essentially all genes of the human genome, harnessing this
      information to enable drug discovery has turned out to be more challenging and
      time consuming than initially anticipated.

PMID- 15990355
TI  - Structures and vibrational frequencies of 2-hydroxy-3-methoxy-5-nitrobenzaldehyde
      and 2-methoxy-1-naphthaldehyde based on density functional theory calculations.
AB  - FT-IR and FT-Raman spectra of 2-hydroxy-3-methoxy-5-nitrobenzaldehyde (HMN) and 2
      methoxy-1-naphthaldehyde (MN) have been recorded in the regions 4000-400 cm(-1)
      and 3500-100 cm(-1), respectively. The molecular structure, conformational
      stability, geometry optimization, vibrational frequencies have been investigated.
      The total energy calculations of HMN and MN were tried for various possible
      conformers. The spectra were interpreted with the aid of normal coordinate
      analysis based on density functional theory (DFT) using B3LYP/6-31G* and B3LYP/6
      311+G** level and basis set combinations and was scaled using various scale
      factors yielding good agreement between observed and calculated frequencies. The
      infrared and Raman spectra were also predicted from the calculated intensities.
      Comparison of the simulated spectra with the experimental spectra provides
      important information about the ability of the computational method to describe
      the vibrational modes.

PMID- 15990356
TI  - Molecular and vibrational structure of 2-mercapto pyrimidine and 2,4-diamino-6
      hydroxy-5-nitroso pyrimidine: FT-IR, FT-Raman and quantum chemical calculations.
AB  - The molecular vibrations of 2-mercapto pyrimidine (MP) and 2,4-diamino-6-hydroxy
      5-nitroso pyrimidine (DAHNP) were investigated in polycrystalline sample, at room
      temperature, by Fourier transform infrared (FT-IR) and FT-Raman spectroscopics.
      In parallel, ab initio and various density functional (DFT) methods were used to
      determine the geometrical, energetic and vibrational characteristics of MP and
      DAHNP. On the basis of B3LYP/6-31G* and B3LYP/6-311+G** methods and basis set
      combinations, a normal mode analysis was performed to assign the various
      fundamental frequencies according to the total energy distribution (TED).
      Simulation of infrared and Raman spectra, utilizing the results of these
      calculations led to excellent overall agreement with observed spectral patterns.
      The scaled quantum mechanical (SQM) approach applying selective scaling of the
      DFT force fields was shown to be superior to the scaling method in its ability to
      ensure correct band assignments and successful simulation of IR and Raman spectra
      including band polarisations and intensity patterns.

PMID- 15990357
TI  - Clinical information technology in hospitals: a comparison between the state of
      Iowa and two provinces in Canada.
AB  - Despite the growing interest in adopting information technology (IT) in
      healthcare, the degree of technology sophistication varies among healthcare
      organizations. Changes in the health care sector and continuous pressure to
      improve the quality of care have driven the evolution of IT in hospitals. This
      paper provides an overview of clinical IT sophistication in a sample of U.S.
      hospitals, and compares clinical IT capacities in this sample with a sample of
      Canadian hospitals. The instrument used for the comparison measures three
      clinical dimensions of IT sophistication: functional sophistication,
      technological sophistication and integration level. Clinical areas that were
      considered include patient management, patient care activities and clinical
      support activities. The comparison between hospitals in Iowa and Canada shows
      differences in clinical IT sophistication between the two settings. Hospitals in
      Iowa appear to have more technologies but fewer computerized processes and
      integration of patient management activities. Technological sophistication
      however, was low in both samples. Our findings confirm the construct validity of
      the measurement instrument and show initial evidence of its generalizability.
      More initiatives using the instrument would lead to enhancement in IT assessment
      tools that can be used for evaluation of IT in relation to patient management and
      quality outcomes.

PMID- 15990358
TI  - Test-retest stability of the magnetic mismatch response (MMNm).
AB  - OBJECTIVE: We investigated the replicability of the magnetically measured
      mismatch negativity (MMNm). METHODS: The MMNm was recorded twice by using a 122
      channel whole-head magnetometer in 15 healthy young adults. The MMNm responses
      for duration, intensity and frequency deviants were analyzed separately in left
      and right hemispheres for the response strength, latency, dipole moment, and
      generator loci. RESULTS: In the right hemisphere, the test-retest correlations
      were statistically significant for all MMNm parameters (r = 0.49-0.89). In the
      left hemisphere, the majority of the MMNm parameters also demonstrated
      statistically significant test-retest correlations (r = 0.61-0.82). In addition,
      the MMNm generator loci were stable for all deviants. CONCLUSIONS AND
      SIGNIFICANCE: The present results are encouraging in terms of both research and
      clinical use of MMNm in studying human auditory discrimination in its normal and
      deteriorated states.

PMID- 15990359
TI  - Time-varying differences in evoked potentials elicited by high versus low spatial
      frequencies: a topographical and source analysis.
AB  - OBJECTIVE: To investigate time-varying differences in visual-evoked potentials
      (VEPs) and dipoles elicited by high versus low spatial frequencies. The main
      question was whether different spatial frequencies are processed in distinct
      cortical areas, especially after 100 ms. An additional question was whether and
      how a hemispheric balance in spatial frequency processing develops over time.
      METHODS: Stimuli were square-wave gratings, with spatial frequencies of 0.75,
      1.5, and 6 c/d. VEPs and dipole models were analyzed at various latencies.
      RESULTS: For the time-window of 80-100 ms, spatial frequency-related differences
      in VEPs and dipoles in posterior regions as reported previously were replicated:
      lower spatial frequencies were associated with more positivity in the VEP and
      with more anterior and radial sources than high frequencies. However, after 100
      ms differences in amplitude, but not in topography and dipoles, were found
      between the different spatial frequencies. Between 180-200 ms a right hemisphere
      dominance was found for all frequencies. CONCLUSIONS: After 100 ms, VEPs in
      response to different spatial frequencies seem to be generated in the same
      cortical areas. Also, no evidence for frequency-related hemispheric
      lateralization was found. SIGNIFICANCE: Insight is provided into the functional
      anatomical basis of longer-latency frequency-related differences in processing.

PMID- 15990360
TI  - Recruitment index as a measure of patient recruitment activity in clinical
      trials.
AB  - Recruitment of patients for clinical trials is one of the major hurdles on the
      way to successful completion of any human research study. Direct comparison of
      recruitment activity in different sites and projects is not easy due to lack of a
      unified measure of recruitment efficacy. The author introduces a new variable,
      the Recruitment Index, which represents the number of days required for an
      average study site in a multicenter study to recruit one analyzable patient. Once
      established in previous studies, an indication-specific Recruitment Index can be
      used for a variety of purposes, e.g. evaluation of efficacy of various
      recruitment strategies, planning duration of recruitment period for a new study,
      or projecting the number of participating sites required to supply a given number
      of analyzable patients within a certain period.

PMID- 15990361
TI  - High prevalence of hepatitis C virus infection and genotype distribution among
      general population, blood donors and risk groups.
AB  - The prevalence of hepatitis C virus (HCV) infection in the general population and
      in various high risk groups in south India was assessed. A total of 258 out of
      3589 (7.1%) subjects (both general and risk groups) tested positive for HCV RNA
      by RT-PCR, while the third generation ELISA detected only 6.1% (221/3589). This
      suggests that a number of cases go unreported, as screening of blood and blood
      products is done primarily by ELISA. Among 124 chronic renal failure (CRF)
      patients with a history of renal transplant or haemodialysis, 37% were found to
      be positive for HCV RNA by RT-PCR. We also found a significantly higher rate of
      transmission of HCV among people exposed to tattooing (2.8%) and pilgrims (5.8%)
      (slashing a cultural practice in one sect of Muslims). In addition, our studies
      also reveal a high prevalence of HCV infection (44%) among patients with Lichen
      planus. The most prevalent genotype observed in our population was 1b (43.4%)
      followed by 3b (30.2%). The other genotype 1a was observed in 16.6% of patients
      followed by 3a observed in 3.4% of the patients. Our findings suggest that HCV
      may be the major cause of post-transplant hepatitis in Indian patients with CRF
      and indicate the necessity for stringent screening procedures for these viral
      infections.

PMID- 15990362
TI  - Telomere shortening is associated with malformation in p53-deficient mice after
      irradiation during specific stages of development.
AB  - The natural ends of linear chromosomes, the telomeres, recruit specific proteins
      in the formation of protective caps that preserve the integrity of the genome.
      Unprotected chromosomes induce DNA damage checkpoint cascades and ultimately lead
      to senescence both in mouse and man in a p53 dependent manner and initial
      telomere length setting therefore determines the proliferative capacity of each
      cell. Yet, only little information is available on telomere biology during
      embryonic development. We have previously shown that the p53 gene plays a crucial
      role in the development of malformations (exencephaly, gastroschisis,
      polydactyly, cleft palate and dwarfism) in control and irradiated mouse embryos.
      Here, we investigated telomere biology and the outcome of radiation exposure in
      wild type (p53+/+) and p53-mutant (p53+/-- and--/--) C57BL mouse foetuses
      irradiated at three different developmental stages. We show that telomeres are
      significantly shorter in malformed foetuses as compared to normal counterparts.
      In addition, our results indicate that the observed telomere attrition is
      primarily associated with p53-deficiency but is also modulated by irradiation,
      more specifically during the gastrulation and organogenesis stages. In
      conclusion, we formulate a hypothesis in which telomere shortening is linked to
      the absence of p53 in mouse foetuses and that when, in the presence of shorter
      telomeres, these foetuses are irradiated, the chance for the occurrence of
      developmental defects increases substantially.

PMID- 15990363
TI  - The efficiency of hypoxanthine excision by alkyladenine DNA glycosylase is
      altered by changes in nearest neighbor bases.
AB  - Alkyladenine DNA glycosylase (AAG) excises a structurally diverse group of
      damaged purines including hypoxanthine, 1,N(6)-ethenoadenine, 3-methyladenine,
      and 7-methylguanine from DNA to initiate base excision repair at these sites.
      Excision occurs in an enzyme.DNA complex in which the damaged base is flipped out
      of the DNA helix into the enzyme active site. To determine whether local DNA
      sequence could affect the overall efficiency of excision of hypoxanthine from
      DNA, single-turnover kinetics of excision, AAG.DNA binding, and melting
      temperatures were measured for DNA substrates that differed in the base pairs
      immediately 5' and 3' to hypoxanthine. When Hx was flanked by a 5'G and a 3'C,
      the efficiency of excision was reduced dramatically in comparison to a duplex
      containing a 5'T and 3'A. The reduction in excision efficiency was largely due to
      a decrease in binding affinity of AAG for DNA. The overall effect of GC versus TA
      nearest neighbors was to magnify the difference in the efficiencies of excision
      of Hx from pairs with thymine and difluorotoluene from a factor of 5 to a factor
      of about 100. In general, DNA substrates that were more stable as indicated by
      higher melting temperatures gave reduced efficiencies of excision of Hx. These
      results are discussed in terms of a model in which the relative stabilities of
      base-flipped versus unflipped complexes contribute the overall efficiency of
      excision and substrate specificity of AAG.

PMID- 15990364
TI  - Mre 11 p nuclease activity is dispensable for telomeric rapid deletion.
AB  - Telomeric rapid deletion (TRD) is an intrachromatid recombination process that
      truncates over-elongated telomeres to the genetically determined average telomere
      length. We have proposed that TRD is initiated by invasion of the 3' G-rich
      overhang into centromere-proximal telomere sequence, forming an intermediate that
      leads to excision of the distal telomere tract. TRD efficiency is dependent on
      Mre 11p and Rad50p, two members of the widely conserved Mre 11p/Rad50p/Xrs2p
      (MRX) complex. To investigate the role of Mre 11p in TRD, we conducted a
      structure/function analysis by testing the TRD rate and precision of mutations
      within known functional domains. We analyzed 12 alleles that disrupt different
      Mre 11p activities. Surprisingly, mutations in essential residues of the nuclease
      domain do not inhibit TRD, effectively ruling out nuclease activity as the source
      of the Mre 11p requirement. Interestingly, loss of Exo1p alone or loss of Exo1p
      in an Mre 11 nuclease deficient background does not eliminate TRD, suggesting the
      presence of an additional nuclease. Second, deletion of DNA binding sites A
      (residues 410--420) and B (residues 644--692) actually enhances the TRD rate.
      Even deletion of both DNA binding domains does not abrogate TRD, although its
      kinetics and precision are variable. This suggests altered DNA binding or a
      conformational defect in the MRX complex may affect the rate of TRD product
      formation and indicates that the DNA binding sites formally act as repressors of
      TRD. Remarkably, the H213Y allele (nuclease motif IV) confers an extraordinarily
      rapid kinetics, with the vast majority of elongated telomeres deleted imprecisely
      in a single round of subculturing. In striking contrast, the P162S allele that
      confers dissolution of the complex also exhibits the null phenotype. These data
      suggest that Mre 11p can act as a positive and negative regulator of TRD in
      context of the MRX complex that is essential for TRD.

PMID- 15990365
TI  - Clinical applications of forced oscillation to assess peripheral airway function.
AB  - Forced oscillation applies external pressures to the respiratory system to
      measure respiratory impedance. Impedance of larger central airways may be
      dissected from that of peripheral airways using multiple oscillation frequencies.
      Respiratory impedance is calculated by computer-assisted methods that yield
      separate resistive and reactive components. The reactive component includes
      respiratory system capacitative and inertive properties, which may be separately
      visualized for clinical purposes using resonance as a rough dividing line. Low
      oscillation frequencies comprise those below resonance, and relate most
      prominently to capacitative properties of peripheral airways. High oscillation
      frequencies comprise those greater than resonance, which relate most prominently
      to inertial properties of larger central airways. Measurements of resistance and
      reactance in patients with peripheral airway disease, before and after
      therapeutic intervention, manifest characteristic patterns of response in low
      frequency resistance and reactance measures that appear to be closely correlated
      with each other. In contrast, changes in large central airways manifest
      resistance change uniformly over low and high frequencies.

PMID- 15990366
TI  - Nocturnal non-invasive positive pressure ventilation: physiological effects on
      spontaneous breathing.
AB  - The dynamic process of how non-invasive positive pressure ventilation (NPPV)
      improves spontaneous ventilation is unclear. Therefore, daytime trends of blood
      gases and breathing pattern were assessed by measurements 0, 0.5, 1, 3, 7, 11 and
      15 h after cessation of nocturnal controlled NPPV in patients with chronic
      hypercapnic respiratory failure. Twelve patients (six COPD/six restrictive) who
      were established on NPPV and 12 controls (six COPD/six restrictive) completed.
      PaCO2 decreased during controlled NPPV (P < 0.02). PaCO2 additionally decreased
      step by step during the first 3 h of spontaneous breathing after switching from
      NPPV to spontaneous breathing (P < 0.05), but remained unchanged in controls. The
      PaCO2 decrease was due to a stepwise increase in tidal volume (P < 0.05) at an
      unchanged breathing frequency. Accordingly, minute ventilation also stepwise
      increased (P < 0.03). There were no significant changes in controls. Improvements
      of PaCO2 and tidal volume occurred even after 5.7 +/- 3.1 days following first
      NPPV trials, but became more evident after 2 months. Maximal inspiratory mouth
      pressures increased in chronic obstructive pulmonary disease (COPD) patients (P <
      0.05), and respiratory drive increased in restrictive patients (P < 0.05)
      following 2 months of NPPV. Lung function parameters and inspiratory impedance
      remained unchanged. Improvements in health-related quality of life were evident
      and were correlated to the decline of elevated bicarbonate levels (r = 0.72, P <
      0.01). In conclusion, there is a stepwise adaptation process lasting 3h when
      switching from nocturnal controlled NPPV to daytime spontaneous breathing in
      which tidal volume increases and PaCO2 drops after an initial PaCO2 decrease
      while on NPPV.

PMID- 15990367
TI  - Method development and validation for monitoring in vivo oxidative stress:
      evaluation of lipid peroxidation and fat-soluble vitamin status by HPLC in rat
      plasma.
AB  - Monitoring in vivo oxidative stress implicates the evaluation of damage and
      defence parameters by well-established, validated methods. We report two
      optimized and validated HPLC methods for measurement of malondialdehyde (MDA) and
      fat-soluble vitamins in rat plasma. For the MDA method, optimization experiments
      of the thiobarbituric acid test resulted in the addition of 1%
      butylhydroxytoluene to the reaction mixture and in a heating time reduction to 40
      min, ensuring inhibition of further lipid peroxidation during the test.
      Validation experiments showed good linearity, precision and recovery. The use of
      HPLC with coulometric array detection technology permits simultaneous and
      sensitive analysis of different fat-soluble vitamins and related compounds
      (tocopherols, retinoids, carotenoids and coenzyme Q10), which are identified by
      both retention time and electrochemical characteristics. Furthermore, this method
      is extended to the analysis of coenzyme Q9, the predominant homologue in rats.
      Validation experiments with rat plasma gave good results.

PMID- 15990368
TI  - Liquid chromatography-mass spectrometry using the hydrogen/deuterium exchange
      reaction as a tool for impurity identification in pharmaceutical process
      development.
AB  - HPLC-MS employing deuterium oxide and common MS-compatible deuterated additives
      in the mobile phase with electrospray ionization is shown to be a viable approach
      for the structural elucidation of impurities in pharmaceutically active agents
      following initial studies with protic mobile phases. This approach incorporates
      the hydrogen/deuterium (H/D) exchange reaction where deuterium is substituted for
      hydrogen at labile sites. Some developmental compounds studied include an amide,
      amine, lipopeptide, indole and methyl sulfone. H/D exchange is rapid and the
      chromatographic performance using deuterated mobile phases is comparable to
      protic counterparts.

PMID- 15990369
TI  - Fast analysis of pravastatin in production media.
AB  - High throughput methods (high performance liquid chromatography and capillary
      electrophoresis) were developed to determine pravastatin in production media. The
      analyses were performed on particle column, monolithic column and silica
      capillary filled with borate buffer pH 9.3 containing 20 mM SDS. All three
      methods successfully separate pravastatin from interfering compounds (matrix,
      mevastatin and 6-epi pravastatin) and runtimes are shorter than 1 min. Solvent
      consumptions for methods using small particle column, monolith column and MECK
      were 132, 510 and 1.5 mL h(-1). The most sensitive was the method using particle
      column (LOD was about 10(-5) mg mL(-1)), followed by the system using monolith
      column (LOD was 2 x 10(-4) mg mL(-1)) and the MECK method (LOD was about 0.02 mg
      mL(-1)).

PMID- 15990370
TI  - Focused lipidomics by tandem mass spectrometry.
AB  - In this paper we performed focused analyses of phospholipids by using the data of
      precursor ion scanning and neutral loss scanning of their polar head groups and
      fatty acyl moieties for the specific search of categorical phospholipids. By
      using precursor ion scanning or neutral loss scanning of polar head groups in the
      positive ion mode, more sensitive identification were obtained than that in the
      negative ion mode. Precursor ion scanning of carbonic anions in the negative ion
      mode was also effective to identify molecular species of phospholipids having
      specified fatty acyl moieties. By using these analytical methods, the detection
      limits of individual metabolites are going up to 5-20-fold of former conventional
      methods. The important factor is that by focusing in some limited categories of
      molecules, detection limit is greatly enhanced, thus minor but important
      molecules can be detected. Moreover, combination of LC-MS/MS and focused scanning
      for head group was revealed to be useful to identify very minor molecular species
      in the focused class of phospholipids.

PMID- 15990371
TI  - Quantitative determination of Astragaloside IV, a natural product with
      cardioprotective activity, in plasma, urine and other biological samples by HPLC
      coupled with tandem mass spectrometry.
AB  - Astragaloside IV is a novel cardioprotective agent extracted from the Chinese
      medical herb Astragalus membranaceus (Fisch) Bge. This agent is being developed
      for treatment for cardiovascular disease. Further development of Astragaloside IV
      will require detailed pharmacokinetic studies in preclinical animal models.
      Therefore, we established a sensitive and accurate high performance liquid
      chromatography (HPLC) coupled with tandem mass spectrometry (LC/MS/MS)
      quantitative detection method for measurement of Astragaloside IV levels in
      plasma, urine as well as other biological samples including bile fluid, feces and
      various tissues. Extraction of Astragaloside IV from plasma and other biological
      samples was performed by Waters OASIS(trade mark) solid phase extraction column
      by washing with water and eluting with methanol, respectively. An aliquot of
      extracted residues was injected into LC/MS/MS system with separation by a
      Cosmosil C18 5 microm, 150 mm x 2.0 mm) column. Acetonitrile:water containing 5
      microM NaAc (40:60, v/v) was used as a mobile phase. The eluted compounds were
      detected by tandem mass spectrometry. The average extraction recoveries were
      greater than 89% for Astragaloside IV and digoxin from plasma, while extraction
      recovery of Astragaloside IV and digoxin from tissues, bile fluid, urine and fece
      ranged from 61 to 85%, respectively. Good linearity (R2>0.9999) was observed
      throughout the range of 10-5000 ng/ml in 0.5 ml rat plasma and 5-5000 ng/ml in
      0.5 ml dog plasma. In addition, good linearity (R2>0.9999) was also observed in
      urine, bile fluid, feces samples and various tissue samples. The overall accuracy
      of this method was 93-110% for both rat plasma and dog plasma. Intra-assay and
      inter-assay variabilities were less than 15.03% in plasma. The lowest
      quantitation limit of Astragaloside IV was 10 ng/ml in 0.5 ml rat plasma and 5
      ng/ml in 0.5 ml dog plasma, respectively. Practical utility of this new LC/MS/MS
      method was confirmed in pilot pharmacokinetic studies in both rats and dogs
      following intravenous administration.

PMID- 15990372
TI  - Solid phase microextraction gas chromatographic analysis of organophosphorus
      pesticides in biological samples.
AB  - Headspace-solid phase microextraction (HS-SPME) was studied and optimised for the
      determination of four common organophosphorus pesticides (OPPs) in biological
      samples. Various parameters controlling SPME were studied: choice of SPME fiber,
      type and content of salt added, preheating and extraction time, desorption time,
      extraction temperature. Capillary gas chromatographic analysis with nitrogen
      phosphorus detection (GC-NPD) facilitates sensitive and selective detection of
      the OPPs: malathion, parathion, methyl parathion and diazinon. Fenitrothion was
      used as the internal standard. The method was applied to the determination of the
      pesticides in human biological specimens: whole blood, blood plasma, urine,
      cerebrospinal fluid, liver and kidney. Limits of detection ranged from 2 to 55
      ng/ml depending on pesticide and type of specimen. The developed methodology
      overcomes limitations and obstacles of conventional methods such as the use of
      organic solvents, the formation of emulsions and the tedious-cumbersome
      procedures. The proposed protocol is seen as an attractive alternative to be used
      in routine toxicological analysis.

PMID- 15990373
TI  - Analysis of mitochondrial DNA in microfluidic systems.
AB  - Abnormalities in mitochondrial function play a major role in many human diseases.
      It is often of critical importance to ascertain what proportion of the
      mitochondria within a cell, or cells, bear a given mutation (the mitochondrial
      "demographics"). In this work, a rapid, novel, on-chip procedure was used, in
      which a restriction enzyme was employed to excise a mitochondrial DNA (mtDNA)
      sequence from plasmid DNA that acted as a prototypical mitochondrial genome. The
      DNA was then denatured, reassembled to form duplexes, fluorescently labelled and
      analysed. This method was able to differentiate between a homogeneous population
      and a heterogeneous population. Using a microfluidic chip, the method could be
      performed in about 45 min, even without robotics or multiplexed operation,
      whereas conventional methods of analysis require days to perform. This method may
      ultimately form the basis for a means of characterizing the mitochondrial
      demographics of a single cell.

PMID- 15990374
TI  - Determination of telithromycin in human plasma and microdialysates by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatography method for the quantitative
      determination of telithromycin in biological fluids is described. The method is
      suitable for plasma and microdialysates from the interstitial space fluid of
      skeletal muscle and subcutaneous adipose tissue. Plasma samples were
      deproteinised with trichloroacetic acid and neutralised with sodium hydroxide.
      Microdialysates were analysed without further preparation step. Telithromycin was
      separated isocratically on a reverse-phase column using acetonitrile-0.03 M
      ammonium acetate, pH 5.2 (43:57, v/v) at a flow rate of 0.8 mlmin(-1), and
      fluorescence detection (excitation 263 nm, emission 460 nm). The calibration
      curve was linear from 0.01 to 5 microgml(-1). Within- and between-day imprecision
      and inaccuracy was < or =10%. The limits of quantification were 0.02 and 0.015
      microgml(-1) for plasma and microdialysates, respectively. Since telithromycin is
      decomposed in aqueous solution at ambient temperature, it is strongly recommended
      to store samples frozen at -80 degrees C, to maintain the temperature at 4
      degrees C during all preparation steps, and to analyse samples within 120 min
      after thawing.

PMID- 15990391
TI  - A computer program for the estimation of protein and nucleic acid sequence
      diversity in random point mutagenesis libraries.
AB  - A computer program for the generation and analysis of in silico random point
      mutagenesis libraries is described. The program operates by mutagenizing an input
      nucleic acid sequence according to mutation parameters specified by the user for
      each sequence position and type of point mutation. The program can mimic almost
      any type of random mutagenesis library, including those produced via error-prone
      PCR (ep-PCR), mutator Escherichia coli strains, chemical mutagenesis, and doped
      or random oligonucleotide synthesis. The program analyzes the generated nucleic
      acid sequences and/or the associated protein library to produce several estimates
      of library diversity (number of unique sequences, point mutations, and single
      point mutants) and the rate of saturation of these diversities during
      experimental screening or selection of clones. This information allows one to
      select the optimal screen size for a given mutagenesis library, necessary to
      efficiently obtain a certain coverage of the sequence-space. The program also
      reports the abundance of each specific protein mutation at each sequence
      position, which is useful as a measure of the level and type of mutation bias in
      the library. Alternatively, one can use the program to evaluate the relative
      merits of preexisting libraries, or to examine various hypothetical mutation
      schemes to determine the optimal method for creating a library that serves the
      screen/selection of interest. Simulated libraries of at least 10(9) sequences are
      accessible by the numerical algorithm with currently available personal
      computers; an analytical algorithm is also available which can rapidly calculate
      a subset of the numerical statistics in libraries of arbitrarily large size. A
      multi-type double-strand stochastic model of ep-PCR is developed in an appendix
      to demonstrate the applicability of the algorithm to amplifying mutagenesis
      procedures. Estimators of DNA polymerase mutation-type-specific error rates are
      derived using the model. Analyses of an alpha-synuclein ep-PCR library and NNS
      synthetic oligonucleotide libraries are given as examples.

PMID- 15990392
TI  - Geranylgeranyl transferase inhibition stimulates anti-melanoma immune response
      through MHC Class I and costimulatory molecule expression.
AB  - Defective antitumor immune responses are frequent consequences of defects in the
      expression of major histocompatibility complex (MHC) class I and costimulatory
      molecules. We demonstrated that statins, inhibitors of HMGCoA reductase, enhance
      mIFN-gamma induced expression of MHC class I antigens on murine B16F10 melanoma.
      GGTI-298, a geranylgeranyl transferase I inhibitor, but not FTI-277, a farnesyl
      transferase inhibitor, mimics this effect of statins. This effect is related to
      peptide transporter protein TAP1 up-regulation. Simultaneously, GGTI-298 induces
      the expression of CD80 and CD86 costimulatory molecules. C3 exoenzyme, which
      selectively inactivates Rho proteins, phenocopies the effects of GGTI-298,
      indicating a role for Rho proteins in these events. Furthermore, the treatment of
      B16F10 cells with GGTI-298 or C3 exoenzyme associated with mIFN-gamma induces in
      vivo tumor growth slowing down in immunocompetent but not in nu/nu syngeneic
      mice. Both in vivo injections and in vitro restimulation of splenocytes with GGTI
      298- and mIFN-gamma-treated B16F10 cells induces an enhancement of specific CD8 T
      lymphocytes labeled by TRP-2/H-2K(b) tetramers. Finally, these effects are not
      limited to mouse models since they were also reproduced in two human melanoma
      cell lines. These observations indicate that protein geranylgeranylation as well
      as Rho protein are critical for costimulatory and IFN-gamma-dependent MHC class I
      molecule expression in melanoma.

PMID- 15990393
TI  - Identification of components of RNAi pathways using the tandem affinity
      purification method.

PMID- 15990394
TI  - Separation of Drosophila RNA silencing complexes by native gel electrophoresis.

PMID- 15990395
TI  - Preparation and analysis of Drosha.

PMID- 15990396
TI  - RNA interference in Caenorhabditis elegans.

PMID- 15990397
TI  - Down-regulating gene expression by RNA interference in Trypanosoma brucei.

PMID- 15990398
TI  - Analysis of double-stranded RNA and small RNAs involved in RNA-mediated
      transcriptional gene silencing.

PMID- 15990399
TI  - Strategies for the design of random siRNA libraries and the selection of anti-GFP
      siRNAs.

PMID- 15990400
TI  - Silencing gene expression with Dicer-generated siRNA pools.

PMID- 15990401
TI  - Inhibition of gene expression in vivo using multiplex siRNA.

PMID- 15990403
TI  - Plasmid-based RNA interference: construction of small-hairpin RNA expression
      vectors.

PMID- 15990402
TI  - Gene silencing by a DNA vector-based RNAi technology.

PMID- 15990404
TI  - siRNA delivery in vivo.

PMID- 15990405
TI  - Peptide-based strategy for siRNA delivery into mammalian cells.

PMID- 15990406
TI  - Lentiviral vector delivery of siRNA and shRNA encoding genes into cultured and
      primary hematopoietic cells.

PMID- 15990407
TI  - Exon-specific RNA interference: a tool to determine the functional relevance of
      proteins encoded by alternatively spliced mRNAs.

PMID- 15990408
TI  - Immunoprecipitation of microRNPs and directional cloning of microRNAs.

PMID- 15990409
TI  - Detection of microRNAs and assays to monitor microRNA activities in vivo and in
      vitro.

PMID- 15990410
TI  - High-throughput analysis of microRNA gene expression using sensitive probes.

PMID- 15990411
TI  - Modification of human U1 snRNA for inhibition of gene expression at the level of
      pre-mRNA.

PMID- 15990412
TI  - Gait characteristics after gait-oriented rehabilitation in chronic stroke.
AB  - PURPOSE: To assess the effects of rehabilitation in thirty-seven ambulatory
      patients with chronic stroke during three weeks in-patient rehabilitation period.
      METHODS: In the intervention group, each patient received 75 min physiotherapy
      daily every workday including 20 minutes in the electromechanical gait trainer
      with body-weight support (BWS). In the control group, each patient participated
      in 45 min conventional physiotherapy daily. Motor ability was assessed with the
      first five items of the Modified Motor Assessment Scale (MMAS1-5) and ten meters
      walking speed. Spatio-temporal gait characteristics were recorded with an
      electrical walkway. RESULTS: The MMAS1-5 (p<0.0005 and p=0.005) and ten meters
      walking time (p<0.0005 and p=0.006) improved in both groups. The improvements in
      MMAS1-5 and ten meters walking time did not differ between the groups (p=0.217
      and p=0.195). Specific gait characteristics improved only in the intervention
      group, as seen in increased Functional Ambulation Profile score (p=0.023),
      velocity (p=0.023), the step lengths (affected side, p=0.011, non-affected side
      p=0.040), the stride lengths (p=0.018, p=0.006) and decreased step-time
      differential (p=0.043). Furthermore, all gait characteristics and other motor
      abilities remained in the discharge level at the six months in the intervention
      group. CONCLUSIONS: It appears that BWS training gives a long-lasting benefit in
      gait qualities even in chronic stroke patients.

PMID- 15990413
TI  - Treatment with magnesium improves reference memory but not working memory while
      reducing GFAP expression following traumatic brain injury.
AB  - PURPOSE: Previous studies have shown that administration of MgCl2 in animal
      models of brain injury significantly improves functional recovery: however, few
      studies have examined cognitive recovery. The present study evaluated the effect
      of MgCl2 pharmacotherapy on recovery of function following medial frontal cortex
      contusion injury. METHODS: Groups of rats were assigned to either MgCl2 (1.0
      mmol/kg) or saline treatment conditions and prepared with contusion injuries or
      shams. Drug treatment was administered 15 min and 24 hr following injury. Rats
      were examined on tests of sensorimotor performance (bilateral tactile adhesive
      removal) and cognitive ability (reference and working memory). RESULTS:
      Administration of MgCl2 following injury significantly reduced the behavioral
      impairments observed on the bilateral tactile removal test. The acquisition of
      reference memory was also significantly improved compared to saline-treated rats;
      however, treatment did not improve working memory performance. Lesion analysis
      revealed that administration of MgCl2 did not significantly reduce lesion size
      compared to saline-treatment. Examination of glial fibrillary acidic protein
      (GFAP) expression showed that MgCl2 did significantly reduce the number of GFAP+
      cells. CONCLUSION: These results indicate that MgCl2 administration significantly
      improved behavioral outcome following injury in a task dependent manner and
      reduced GFAP expression.

PMID- 15990414
TI  - Sutures as longitudinal guides for the repair of nerve defects--influence of
      suture numbers and reconstruction of nerve bifurcations.
AB  - PURPOSE: We investigated whether sutures could guide regeneration across
      bifurcated nerve defects and how the number of sutures influenced regeneration.
      METHODS: Bilateral ten mm defects in the rat sciatic nerve were bridged by either
      two or six laps of longitudinal (8/0 polyglactin) sutures. Bilateral ten mm
      defects including the bifurcation of tibial and peroneal nerves were bridged by
      two laps to the tibial and four laps to the peroneal nerve on one side and vice
      versa on the other. Evaluation of tetanic force, weights of the gastrocnemius and
      caudal tibial muscles and morphometry of the nerves were performed at twelve
      weeks. RESULTS: Simple defects bridged by six laps yielded a significantly
      greater number of myelinated axons compared to two laps. In the bifurcated
      defects a well defined two branched nerve structure was formed in all cases
      between the sciatic nerve and its peroneal and tibial branches. However, in the
      bifurcated model the tibial nerve attracted more axons than the peroneal
      irrespective of the number of suture laps. CONCLUSIONS: There is no simple
      correlation between the number of sutures and the number of regenerating axons
      but two suture laps may be insufficient for the repair of a rat sciatic nerve.
      Sutures supported reconstruction of new fascicles across bifurcated nerve
      defects.

PMID- 15990415
TI  - Compensatory changes in cortical cholinergic innervation in the rat following an
      immunotoxic lesion.
AB  - PURPOSE: To investigate the plastic capacity of the cholinergic system in a
      partial animal model of Alzheimer's disease. METHODS: Rats received unilateral
      lesions of the horizontal diagonal band of Broca (HDB) using a cholinergic
      specific toxin, 192 IgG-saporin. After the appropriate survival time (2, 4, 8, 12
      and 24 weeks post-lesion) rats were sacrificed and the brains were prepared for
      histology. Immunocytochemical and morphometric techniques were employed to
      quantify the cholinergic neurons surviving the lesion and to measure the density
      of cortical cholinergic fibers. RESULTS: Cell counts revealed on average a 60%
      reduction in cholinergic neurons on the lesioned side, compared to the spared
      side. This cell loss was permanent, that is, there was no significant change in
      the amount of cell loss over time. In correlation with this cell loss,
      cholinergic fibers in the target area, the entorhinal cortex (EC), were also
      reduced such that the density of acetylcholinesterase (AChE)-stained fibers on
      the lesioned side was 44% of the spared side. The density of cholinergic fibers
      in the EC increased significantly between 2 and 12 weeks post-lesion (p=0.0216)
      but remained stable at that level by 24 weeks after the lesion. CONCLUSIONS:
      Following a cholinergic-specific lesion, a compensatory mechanism is activated in
      the basal forebrain cholinergic system, such that surviving neurons, projecting
      to the same target, extend their terminals to occupy the denervated area. It
      remains to be investigated whether these sprouts are able to establish proper
      synaptic connections and make a functional recovery in this particular system.

PMID- 15990416
TI  - On regenerative and collateral sprouting to hind limb digits after sciatic nerve
      injury in the rat.
AB  - PURPOSE: This study examines the proportions of regenerative and collateral
      sprouting to the skin after peripheral nerve injury. METHODS: In the first
      experimental paradigm, primary afferent neurones were pre-labelled with Diamidino
      Yellow (DY), injected in digit 3, followed by sciatic nerve section and repair.
      After three months of regeneration, digit 3 was re-injected with Fast Blue (FB)
      to label regenerating cells. Fluoro-Gold (FG) was applied to the femoral (FEM)
      and musculocutaneous (MC) nerves four days later to quantify their contribution
      to the innervation. In the second experimental paradigm, sciatic nerve was first
      sectioned and repaired. Three months later, the sciatic was resected, and digit 3
      injected with FB. After four more days, FEM and MC were resected and FG injected
      in all digits. RESULTS: Neurones in dorsal root ganglion (DRG) L5 had a higher
      rate of correct reinnervation of digit 3 (44-72%) than neurones in DRG L4 (14
      44%). Like in control cases, only occasional axons were traced from the FEM and
      MC. In the second experiment, only occasional labelled neurones appeared.
      CONCLUSIONS: The results indicate differences in the capacity for correct
      peripheral sensory reinnervation between segmental levels, and that in this model
      collateral sprouting was practically non-existent compared to regenerative
      sprouting.

PMID- 15990417
TI  - Grip force tracking system for assessment and rehabilitation of hand function.
AB  - The aim of the paper is to present a novel tracking system for the assessment and
      training of grip force control. The system consists of two force measuring units
      of different shapes, which can be connected to a personal computer for visual
      feedback and data acquisition. We present the results of the assessment of the
      grip force control in 32 healthy subjects of different age groups and preliminary
      results obtained in a patient after head-injury who was treated with Botulinum
      Toxin for hand spasticity. The proposed tracking system was also applied as a
      training tool in 10 post-stroke patients to possibly improve their grip force
      control. The results in healthy subjects showed significant differences in grip
      force control among different age groups. In the patient after Botulinum-Toxin
      treatment the method revealed noticeable effects of the therapy on the patient's
      tracking performance. Training with the tracking system showed considerable
      improvements in the grip force control in 8 out of 10 stroke patients. The
      proposed tracking method is aimed to be used in connection with different
      rehabilitation therapies (e.g. physiotherapy, functional electrical stimulation,
      drug treatment) to follow the influence of the therapy on patient's muscular
      strength and grip force control.

PMID- 15990418
TI  - A soft decision algorithm for obstructive sleep apnea patient classification
      based on fast estimation of wavelet entropy of RRI data.
AB  - A soft decision algorithm for Obstructive Sleep Apnea (OSA) patient
      classification using R-R interval (RRI) data is investigated. This algorithm is
      based on fast and approximate estimation of the entropy of the wavelet-decomposed
      bands of the RRI data. The classification is done on the whole record as OSA
      patient or non-patient (normal). The ratio of the estimated entropy of the low
      frequency (LF) band to that of the very-low frequency (VLF) band is used as a
      classification factor. RRI data used in this work are drawn from MIT database.
      The MIT trial records are used to set the threshold value of the classification
      factor using the Receiver Operating Characteristics (ROC). This threshold value
      is used then to classify the MIT challenge (test) records to obtain the
      efficiency of classification. The new algorithm classifies correctly 30/30 of MIT
      test data using different wavelet filters. Comparison of the results of different
      wavelet filters is done in terms of complexity and distance parameters. The
      method is also compared with other two techniques using wavelets in their
      analysis. The consistency of the results is examined using the leave-one-out
      technique.

PMID- 15990420
TI  - The emergence of radically new health care technologies: inventive users as
      innovation networkers.
AB  - Besides a large body of research on user innovation, little is known which role
      users play in the emergence of radically new health care technologies. Such
      technologies are 'new-to-the-world', highly complex, shift market structures, and
      require user learning as they often induce significant behaviour changes on side
      of the users. In a multi-case-study-analysis we identified an 'entrepreneurial'
      role of inventive users. Those surgeons that were the original inventors of
      radically new health care technologies established and organized the required
      innovation networks. They identified relevant partners, formed a network of
      experts with complementary knowledge bases, and coordinated this network. These
      innovation networks were required to transform their radically new ideas into
      first physical prototypes. To better understand the observed phenomenon we
      analysed factors that might explain this exclusive role. We find that a high
      problem pressure, an active role of users in the idea generation phase, a high
      degree of innovativeness of the prospective product, and missing competencies as
      well as missing resources explain the networking activities of inventive users.
      The findings shed light on the role of users in the emergence of radically new
      health care technologies.

PMID- 15990421
TI  - Three dimensional stress analysis of diabetic insole: a finite element approach.
AB  - Current research in foot biomechanics includes studies on prevention of
      recurrence of neuropathic foot ulcers. This paper attempts to prescribe
      accommodative insoles, which reduce plantar pressure levels particularly under
      the hallux. There is little quantitative information available regarding the
      effects of insole materials on reduction of plantar pressure. The insole models
      available in the literature are mostly two-dimensional (2-D). Hence, there is a
      need to develop a 3-D model with actual geometry which includes sufficient
      details. In this study a three-dimensional (3-D) model of the insole was
      constructed. A linear and non-linear static analysis using finite element method
      (FEM) was performed. Results were compared for different materials such as
      Silicon Gel, Plastozot, Polyfoam, and Ethinil Vinyl Acetate (EVA). Our 3-D finite
      element model was constructed using 16170 ten-node tetrahedral, mixed U-P
      (displacement-pressure), hyperelastic, solid elements. Four different
      hyperelastic and foam materials were used and compared and the loading condition
      was based on the mid-stance phase of the gait. This research has shown that most
      of these materials are very effective in terms of reduction of plantar stress
      concentrations. The technique used in this research provides a promising approach
      to understanding of behavior of insole materials and suggests a design guideline
      for therapeutic footwear and orthoses.

PMID- 15990422
TI  - When microchip implants do more than drug delivery: blending, blurring, and
      bundling of protected health information and patient monitoring.
AB  - Although currently in the research stage, scientists argue that drug-releasing
      microchip implants are on the horizon for future patients. This paper presents
      ethical reflection on these implants and identifies specific areas of concern;
      namely, patient monitoring and tracking, and patient privacy and confidentiality.
      It is foreseeable that drug delivery chips could be multifunctional with the
      overt or covert addition of sensors that monitor more than just the bloodstream
      concentrations of prescribed drugs (e.g., cotinine and alcohol in non-compliant
      patients, patient location via radio frequency or global positioning satellite).
      Similarly, it is foreseeable that these chips could be embedded with a patient's
      protected health information that could potentially be accessed and used by
      unauthorized persons. While drug delivery microchips are theoretically convenient
      and accurate for dosing, and might offer faster drug delivery with fewer side
      effects, ethical issues loom and should be contemplated now, while the technology
      is still under development.

PMID- 15990423
TI  - Design and implementation of a telemedicine system using Bluetooth protocol and
      GSM/GPRS network, for real time remote patient monitoring.
AB  - This paper introduces the design and implementation of a generic wireless and
      Real-time Multi-purpose Health Care Telemedicine system applying Bluetooth
      protocol, Global System for Mobile Communications (GSM) and General Packet Radio
      Service (GPRS). The paper explores the factors that should be considered when
      evaluating different technologies for application in telemedicine system. The
      design and implementation of an embedded wireless communication platform
      utilising Bluetooth protocol is described, and the implementation problems and
      limitations are investigated. The system is tested and its telecommunication
      general aspects are verified. The results showed that the system has (97.9 +/-
      1.3)% Up-time, 2.5 x 10(-5) Bit Error Rate, 1% Dropped Call Rate, 97.4% Call
      Success Rate, 5 second transmission delay in average, (3.42 +/- 0.11) kbps
      throughput, and the system may have application in electrocardiography.

PMID- 15990424
TI  - Construction of a speed feedback therapy system to improve cognitive impairment
      in elderly people with dementia: a preliminary report.
AB  - The objective of this study was to construct a speed feedback therapy system with
      a bicycle ergometer for elderly people with dementia and to assess its
      feasibility. There were 17 elderly people with dementia in the experimental group
      and 10 in the control group. In the experimental group, we used the system we
      devised in this study together with an ordinary ergometer. The Mini-Mental State
      Examination was performed before and after the interventions to evaluate their
      effects. No adverse effects occurred during use of the system. No changes in Mini
      Mental State Examination scores were observed in the control group, but they
      increased significantly after the interventions in the experimental group. These
      results suggest that the speed feedback therapy system can be used as an
      intervention method to improve cognitive impairment in elderly people with
      dementia.

PMID- 15990425
TI  - Functional disabilities profile of chinese elderly people with Alzheimer's
      disease - a validation study on the chinese version of the disability assessment
      for dementia.
AB  - This study aimed to determine the validity and applicability of the Chinese
      version of the Disability Assessment for Dementia (CDAD) in the Chinese elderly
      population. The original English version was translated and modified to a 47-item
      scale to suit the societal and cultural background of the Chinese population. The
      CDAD was administered to 169 community-residing Chinese elderly people with
      Alzheimer's disease (AD) and demonstrated high internal consistency (Cronbach's
      alpha=0.91), excellent test-retest reliability (intraclass correlation, ICC=0.99)
      and excellent interrater reliability (ICC=0.98). The functional disabilities
      profile of the same sample was examined. The CDAD had a high negative correlation
      with the Global Deterioration Scale (GDS; Spearman's rho=-0.89, p<0.001). ANOVA
      and post hoc comparisons showed there were significant differences in the mean
      CDAD scores across different GDS stages. To study the construct validity, the
      CDAD was administered concurrently with several instruments. The Instrumental
      Activities of Daily Living subscore of the CDAD had a high correlation with the
      Instrumental Activities of Daily Living Scale (r=0.94,p<0.001), and the
      Activities of Daily Living subscore of the CDAD had a high correlation with the
      Modified Barthel Index (r=0.82, p<0.001). A moderate correlation (r=0.60,
      p<0.001) with the Cantonese version of the Mini Mental State Examination was also
      found. Analysis of the relationship with sociodemographic factors indicated that
      the CDAD was not correlated with gender and education, and that the correlation
      with age was low. The CDAD was shown to be a reliable and valid instrument in
      assessing the functional disabilities of community-residing elderly subjects with
      AD in the Chinese population.

PMID- 15990426
TI  - Galantamine prolonged-release formulation in the treatment of mild to moderate
      Alzheimer's disease.
AB  - The primary objective of this study was to evaluate the efficacy and tolerability
      of a flexible dosing regimen (16 or 24 mg/day) of galantamine prolonged-release
      capsule (PRC) compared with placebo in subjects with mild to moderate Alzheimer's
      disease (AD). This phase III, double-blind, placebo- and active-controlled,
      parallel-group trial randomized 971 patients to treatment for 6 months. Efficacy
      endpoints included change in the 11-item cognitive subscale of the Alzheimer's
      Disease Assessment Scale (ADAS-cog/11), Clinician's Interview-Based Impression of
      Change plus caregiver input (CIBIC-plus), Alzheimer's Disease Cooperative Study
      Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI)
      scores. Galantamine was associated with significant improvements in the ADAS
      cog/11 score but not in the CIBIC-plus or NPI scores. Galantamine PRC was
      associated with significant improvement in ADCS-ADL scores. Galantamine PRC had
      similar tolerability and safety profiles compared with twice-daily galantamine,
      and when administered as a once-daily flexible dosing regimen of 16 or 24 mg/day,
      was demonstrated to be as safe and effective for the treatment of mild to
      moderate AD.

PMID- 15990427
TI  - Interpersonal aspects of personality disorders in opioid-dependent patients: the
      convergence of the ICL-R and the SIDP-IV.
AB  - This study aims to establish the convergence of the empirically based Diagnostic
      Statistical Manual (DSM)- and theory-based interpersonal behavioral approaches to
      personality, in opioid-dependent patients (n = 110), with the use of the
      Structured Interview for DSM-IV Personality [Pfohl et al.: Structured Interview
      for DSM-IV PD. Iowa City, UICM, 1995] and the Interpersonal Checklist-Revised
      (ICL-R) [DeJong and VandenBrink: ICL-R. St. Oedenrode/NL, Novadic, 1998]. As
      hypothesized, based on prior research, we found the two approaches to be
      complementary rather than interchangeable. However, some overlap was found
      between the SIDP-IV dimensions and the ICL-R, mainly with rebellious/distrustful,
      reserved/silent and masochistic/self-effacing styles. Results indicate that drug
      dependence in itself is not a predictor of interpersonal style, while personality
      pathology is. Patients with a personality disorder (PD) perceive themselves as
      hostile and submissive, while patients without a PD view themselves as friendly
      and controlling. The SIDP-IV seems informative in classifying PDs, in addition
      guidelines for behavioral change, in addicted patients, were provided based on
      the ICL-R.

PMID- 15990428
TI  - Individuals seeking treatment for cannabis-related problems in Ontario:
      demographic and treatment profile.
AB  - We report on the extent of cannabis treatment-seeking within an addiction
      treatment system in Canada. Data represent all new admissions in fiscal year 2000
      to substance abuse treatment agencies in the province of Ontario (n = 47,995).
      Analyses examine the prevalence of cannabis problems by demographic and treatment
      characteristics and provide contrasts with other client subgroups (alcohol,
      cocaine, and opiates). Clients reporting cannabis as their primary problem
      substance (13%) were more likely to be male, single, under age 20 and in high
      school. Legal system involvement and school- or family-based pressure to enter
      treatment were commonly reported, but less so by older cannabis clients. The
      distinctiveness of these clients within the larger treatment system raises
      questions of the relevance to cannabis clients of interventions designed for
      other substance-abusing populations.

PMID- 15990429
TI  - Tracing selection effects in three non-probability samples.
AB  - Snowball sampling and targeted sampling are widely applied techniques to recruit
      samples from hidden populations, such as problematic drug users. The disadvantage
      is that they yield non-probability samples which cannot be generalised to the
      population. Despite thorough preparatory mapping procedures, selection effects
      continue to occur. This paper proposes an interpretation frame that allows
      estimating the direction of selection bias after data collection. Critical
      examination of the recruitment procedure and comparison with statistical and non
      statistical external data sources are the core features of the interpretation
      frame. Applying the interpretation frame increases insight into the reliability
      of the results and allows to estimate where selection bias may have occurred.

PMID- 15990430
TI  - Efficacy of an intensive outpatient rehabilitation program in alcoholism:
      predictors of outcome 6 months after treatment.
AB  - Treatment of alcohol-dependent patients was primarily focused on inpatient
      settings in the past decades. The efficacy of these treatment programs has been
      evaluated in several studies and proven to be sufficient. However, with regard to
      the increasing costs in public healthcare systems, questions about alternative
      treatment strategies have been raised. Meanwhile, there is growing evidence that
      outpatient treatment might be comparably effective as inpatient treatment, at
      least for subgroups of alcohol dependents. On that background, the present study
      aimed to evaluate the efficacy of a high-structured outpatient treatment program
      in 103 alcohol-dependent patients. 74 patients (72%) terminated the outpatient
      treatment regularly. At 6 months' follow-up, 95% patients were successfully
      located and personally re-interviewed. Analyses revealed that 65 patients (64%)
      were abstinent at the 6-month follow-up evaluation and 37 patients (36%) were
      judged to be non-abstinent. Pre-treatment variables which were found to have a
      negative impact (non-abstinence) on the 6-month outcome after treatment were a
      higher severity of alcohol dependence measured by a longer duration of alcohol
      dependence, a higher number of prior treatments and a stronger alcohol craving
      (measured by the Obsessive Compulsive Drinking Scale). Further patients with a
      higher degree of psychopathology measured by the Beck Depression Inventory
      (depression) and State-Trait Anxiety Inventory (anxiety) relapsed more often. In
      summary, results of this study indicate a favorable outcome of socially stable
      alcohol-dependent patients and patients with a lower degree of depression,
      anxiety and craving in an intensive outpatient rehabilitation program.

PMID- 15990431
TI  - Risk Factors and predictors of human immunodeficiency virus infection among
      injection drug users.
AB  - BACKGROUND/AIM: Injection drug users (IDUs) have a high risk of acquiring an
      infection with the human immunodeficiency virus (HIV). To improve counseling and
      prevention, a better understanding of risk factors and predictors for an
      infection must be gained. This retrospective study has the aim to determine the
      risk factors for acquisition of HIV infection other than sharing of
      needles/syringes. METHODS: The study population consisted of all patients
      admitted to the detoxification unit between 1991 and 1996 who met ICD-10 criteria
      for opioid dependency, who reported to share needles, and who agreed to have an
      antibody test. Possible risk factors were assessed by interview. Cross tables
      based on bivariate logistic regression were constructed to estimate the relative
      odds. Multiple logistic regression modeling procedures were used to adjust
      possible confounding factors. RESULTS: A total of 1,049 out of 1,656 patients
      admitted were included into the study. 4.8% of the patients were HIV-1
      seropositive. The prevalence was higher among older patients and among patients
      living with a significant other substance drug user with substance dependency,
      after a longer duration of drug use, and after coinfection with hepatitis B virus
      and/or hepatitis C virus (HCV). Using multiple logistic regression analyses and
      including all individually significant risk factors, we found only coinfection
      with HCV to remain significant. 92% of the HIV-infected patients were also HCV
      infected. In the group younger than 23 years of age, a total of 53.5% of the IDUs
      were still seronegative for HIV, hepatitis A and B virus, and HCV. CONCLUSIONS:
      Despite the high rate of HCV coinfection (92%) in HIV-infected patients, we found
      more than 50% of IDUs younger than 23 years to be neither infected with HCV nor
      with HIV. Early prevention strategies against infectious diseases should
      especially focus on young IDUs.

PMID- 15990432
TI  - Use of slow-release oral morphine for the treatment of opioid dependence.
AB  - AIMS: In addition to methadone, other synthetic opioids are now available for the
      treatment of opioid dependence. The study investigated the treatment satisfaction
      of oral slow-release morphine for maintenance therapy in opioid-dependent
      patients in an open-label 3-week study. DESIGN: We evaluated the treatment
      satisfaction of oral slow-release morphine hydrochloride for 3 weeks in 110
      patients meeting the diagnosis of opioid dependence (DSM-IV 304.0) or
      polysubstance dependence (DSM-IV 304.9). MEASUREMENTS: Primary outcome measures
      were the study retention rate, urinalysis for additional illicit consumption
      other than heroin, cravings and withdrawal symptoms 24 h after the last intake of
      the medication (duration of action of treatment). FINDINGS: In total, 103
      patients completed the study, representing a retention rate of 94%. Patients
      reported significant improvements in somatic complaints, as well as significant
      reductions in heroin and cocaine cravings (p < 0.0001) and in additional
      consumption of cocaine in supervised urinalysis (p = 0.0083). Additional illicit
      consumption of benzodiazepines remained unchanged. CONCLUSIONS: The high study
      retention rate implies a good acceptance of slow-release acting oral morphine.
      However, randomised, double-blind, double-dummy studies with a longer
      investigational period are needed to meet criteria for evidence-based medicine.

PMID- 15990433
TI  - Within-patient variability in clinical presentation of gamma-hydroxybutyrate
      withdrawal: a case report.
AB  - The emergence of gamma-hydroxybutyrate (GHB) dependence in the UK is described,
      with specific reference to a case study of serial episodes of GHB withdrawal.
      Symptoms are broadly similar to those for alcohol withdrawal, and rapid
      deterioration into delirium is common in severe dependence. This case report
      reflects the variability in clinical presentation of GHB withdrawal and response
      to treatment, even within the same patient. It is concluded that GHB withdrawal
      requires vigorous clinical management, preferably on an elective basis, in an
      inpatient setting if dependence is severe.

PMID- 15990434
TI  - Alcoholic case of central pontine myelinolysis with mainly cerebellar signs.
AB  - The etiology of central pontine myelinolysis (CPM) is usually related to rapid
      correction of hyponatremia and alcoholism. Here a case with CPM predominated by
      cerebellar signs is described, and the neuropsychological assessment of the case
      is presented as well. Blood biochemistry revealed a normal sodium level and
      neuropsychological examination revealed impairment in attention and
      concentration, reduced immediate memory span, and impaired delayed recall.
      Further studies are needed to discover whether these neuropsychological signs are
      specific for CPM or due to alcoholism in general.

PMID- 15990435
TI  - [Therapy of breast cancer--change from radical to quality-controlled
      individualized treatment].
AB  - The treatment of breast cancer is changing continually. Thus, sentinel lymph node
      dissection is considered today as standard in the therapy of small unifocal
      breast carcinoma with clinically negative axillary lymph nodes. Concerning
      adjuvant therapy, the 9th Early Adjuvant Breast Cancer Meeting, along with a
      consensus conference, took place in Saint Gall on January 26-29, 2005. The
      publication of the corresponding congress report is expected for early summer of
      2005.

PMID- 15990436
TI  - [Limitations of sentinel lymph node biopsy in breast cancer].
AB  - Sentinel lymph node biopsy is a widely accepted new surgical procedure in the
      treatment of early breast cancer. However, not only numerous details of the
      technique, but also limitations of the method, such as maximal tumor size,
      multifocal disease, accuracy following neoadjuvant chemotherapy and
      appropriateness in ductal carcinoma in situ are being debated. Recent multicenter
      studies could establish the lower morbidity of sentinel lymph node biopsy
      compared to axillary clearance as well as the false-negative rate which lies
      between 7 and 9.7%. In unifocal T1 disease with clinically negative axillary
      lymph nodes, the method is considered to be standard of care. Evidence is growing
      that it may also be appropriate in larger and multifocal tumors while the method
      is unreliable after neoadjuvant chemotherapy.

PMID- 15990437
TI  - [Aromatase inhibitors in the adjuvant therapy of breast cancer].
AB  - Breast cancer is a hormone-sensitive cancer and in most post-menopausal women
      hormone receptor positive. The hormone receptor status is a highly valid
      predictive marker of responsiveness to endocrine therapy. The standard adjuvant
      therapy in patients with hormone-receptor-positive breast cancer is the selective
      estrogen receptor modulator tamoxifen. Third-generation aromatase inhibitors are
      accepted as a treatment option for metastatic breast cancer. However, results
      from recent studies show also a benefit of this type of drugs for disease-free
      survival with fewer adverse reactions in the adjuvant therapy. Therefore a new
      therapeutic field opens for the use of 3rd-generation aromatase inhibitors. This
      will lead to an expansion of the indication, but the question of modality -- up
      front, switch or extended therapy -- remains to be resolved.

PMID- 15990438
TI  - Elderly breast cancer patients: adjuvant chemotherapy and adjuvant endocrine
      therapy.
AB  - Older women have unfortunately been underrepresented in breast cancer clinical
      trials, with the majority of studies being restricted to patients younger than 70
      years. Elderly patients are an inhomogeneous group and frequently suffer from
      comorbidities and/or impaired organ functions. These facts may often lead to
      death from causes other than cancer, thus nullifying any possible benefit of
      adjuvant treatment; furthermore, they render extrapolation of standard treatment
      recommendations to the elderly potentially hazardous, particularly with respect
      to chemotherapy. Specific clinical trials are therefore needed to investigate
      adjuvant treatments tailored for the heterogeneous older population.

PMID- 15990440
TI  - [From the concept of guilt to the value-free notification of errors in medicine.
      Risks, errors and patient safety].
AB  - The number of liability cases but also the size of individual claims due to
      alleged treatment errors are increasing steadily. Spectacular sentences,
      especially in the USA, encourage this trend. Wherever human beings work, errors
      happen. The health care system is particularly susceptible and shows a high
      potential for errors. Therefore risk management has to be given top priority in
      hospitals. Preparing the introduction of critical incident reporting (CIR) as the
      means to notify errors is time-consuming and calls for a change in attitude
      because in many places the necessary base of trust has to be created first. CIR
      is not made to find the guilty and punish them but to uncover the origins of
      errors in order to eliminate them. The Department of Anesthesiology of the
      University Hospital of Basel has developed an electronic error notification
      system, which, in collaboration with the Swiss Medical Association, allows each
      specialist society to participate electronically in a CIR system (CIRS) in order
      to create the largest database possible and thereby to allow statements
      concerning the extent and type of error sources in medicine. After a pilot
      project in 2000-2004, the Swiss Society of Gynecology and Obstetrics is now
      progressively introducing the 'CIRS Medical' of the Swiss Medical Association. In
      our country, such programs are vulnerable to judicial intervention due to the
      lack of explicit legal guarantees of protection. High-quality data registration
      and skillful counseling are all the more important. Hospital directors and
      managers are called upon to examine those incidents which are based on errors
      inherent in the system.

PMID- 15990439
TI  - [Consensus Meeting of the 9th International Conference on Primary Therapy of
      Early Breast Cancer (St. Gall, January 26-29, 2005)].
AB  - More than 4,000 participants attended the congress and the consensus conference
      2005, an increase of more than 1,000 participants. The conference had 2
      highlights. (1) The presentation of the first results of the study BIG 1-98 --
      letrozole as adjuvant, endocrine therapy in postmenopausal women with hormone
      sensitive breast cancer -- showed a relative risk reduction in the disease-free
      survival of 19% when compared to tamoxifen. (2) The consensus conference adopted
      2 new relevant developments: endocrine responsiveness as criterion for both
      chemotherapy and endocrine therapy. The newly introduced electronic voting system
      allowed the audience to observe the forming of the panelists' opinions on more
      than 100 predefined questions.

PMID- 15990441
TI  - Higher basal adiponectin levels are associated with better ovarian response to
      gonadotropin stimulation during in vitro fertilization.
AB  - AIMS: To measure adiponectin levels in the serum samples from day 3 of the
      menstrual cycle prior to the administration of gonadotropin during in vitro
      fertilization, and to measure any correlations between adiponectin levels and the
      number of oocytes retrieved, body weights and body mass indexes. Also, to examine
      whether there is a difference in adiponectin levels between women who conceive
      and those who do not. METHODS: In a case-control design, 56 women undergoing in
      vitro fertilization procedures were included in this study: 28 women who
      conceived were matched with 28 women who did not conceive. Adiponectin levels in
      serum were determined by radioimmunoassay and compared. RESULTS: The adiponectin
      levels were positively correlated with the number of oocytes retrieved (r =
      0.306, p = 0.022), but negatively correlated with body mass index and body weight
      (r = -0.367, p = 0.005; r = -0.326, p = 0.014). No significant correlations were
      found between the number of oocytes retrieved and body mass index or body weight
      (r = 0.020, p = 0.882; r = 0.069, p = 0.613). We further observed that
      adiponectin levels in women who conceived (23.0 +/- 2.0 microg/ml) were found to
      be significantly higher (p = 0.026) than those in women who did not conceive
      (17.3 +/-1.4 microg/ml). The number of oocytes retrieved from women who conceived
      (13.3 +/- 0.9) was also higher than that in women who did not (10 +/- 1.2; p =
      0.029). CONCLUSIONS: The number of oocytes retrieved was found to correlate
      positively with the adiponectin levels on the day prior to the administration of
      gonadotropin. In addition, basal adiponectin levels were significantly higher in
      those women who conceived. Therefore, adiponectin is a better marker of adequate
      follicular development during in vitro fertilization than is body weight or body
      mass index.

PMID- 15990442
TI  - Role of extracellular superoxide dismutase in patients under maintenance
      hemodialysis.
AB  - BACKGROUND: It has been well documented that free radical injury is involved in
      the progression of chronic renal failure. Extracellular superoxide dismutase (EC
      SOD), localized on the endothelial cell surface, plays an important role in
      reducing oxidative stress especially in the vessels by binding to the endothelial
      cell surface via the heparin-binding domain. Although EC-SOD Arg213Gly, which
      cannot bind on endothelial cells, has been considered a polymorphism, the effect
      of EC-SOD on hemodialysis patients has not been well examined. METHODS: In 178
      hemodialysis patients, the following examinations were performed. EC-SOD
      Arg213Gly was examined by polymerase chain reaction (PCR)-induced mutation
      restriction analysis (PCR-IMRA). As indexes of atherosclerosis, the annual
      progression in intima-media thickness (DeltaIMT), plaque score, pulse wave
      velocity (PWV) and plasma-oxidized low-density lipoprotein (OxLDL) values were
      examined. RESULTS: PCR-IMRA revealed that 20 of 178 patients possessed the
      mutation (11.2%), and the incidence was about twice as high as that in a
      previously reported Japanese population. Although there were no statistical
      differences in plaque score and PWV with and without EC-SOD Arg213Gly, DeltaIMT
      and plasma OxLDL values in patients with EC-SOD Arg213Gly were significantly
      higher than those in patients without the mutation. CONCLUSION: EC-SOD Arg213Gly
      is an accelerating factor for the progression of renal failure and
      atherosclerosis.

PMID- 15990443
TI  - Increasing incidence of multiple sclerosis in the province of Sassari, northern
      Sardinia.
AB  - Sardinia is a high-risk area for multiple sclerosis (MS), with prevalence rates
      of 150 per 100,000 population. The study included 689 MS patients (female-male
      ratio 2.6) with disease onset between 1965 and 1999 in the province of Sassari.
      The mean annual incidence rate increased significantly from 1.1 per 100,000
      population in 1965-1969 to 5.8 in 1995-1999, with no significant difference for
      gender and province sub-areas. The mean age at onset increased significantly
      during the same period from 25.7 to 30.6 years, while the proportion of patients
      with progressive initial course declined over time. The marked increase of MS
      incidence and the change of MS clinical phenotype over time cannot be explained
      by ascertainment bias only, thus pointing to a corresponding change in the
      distribution of exogenous risk factors in this highly genetically stable
      population.

PMID- 15990444
TI  - The reasons for geographic and racial differences in stroke study: objectives and
      design.
AB  - The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a
      national, population-based, longitudinal study of 30,000 African-American and
      white adults aged > or =45 years. The objective is to determine the causes for
      the excess stroke mortality in the Southeastern US and among African-Americans.
      Participants are randomly sampled with recruitment by mail then telephone, where
      data on stroke risk factors, sociodemographic, lifestyle, and psychosocial
      characteristics are collected. Written informed consent, physical and
      physiological measures, and fasting samples are collected during a subsequent in
      home visit. Participants are followed via telephone at 6-month intervals for
      identification of stroke events. The novel aspects of the REGARDS study allow for
      the creation of a national cohort to address geographic and ethnic differences in
      stroke.

PMID- 15990445
TI  - Amyotrophic lateral sclerosis mortality in the United States, 1979-2001.
AB  - The etiology of nonfamilial amyotrophic lateral sclerosis (ALS) remains unknown.
      Earlier studies have suggested an increase in the incidence of ALS over time. We
      performed a retrospective analysis of ALS-associated death rates and trends in
      the United States for 1979-2001 using death records from the national multiple
      cause-of-death database. The US average annual age-adjusted ALS death rate was
      1.84 per 100,000 persons for 1979 through 1998. Most deaths were among adults >
      or =65 years of age and the median age at death was 67 years. A small overall
      increase in the death rate was observed primarily between 1979 and 1983, with a
      subsequent plateau. This slight change in the overall rate reflected apparent
      increases in the rates among those persons > or =65 years of age, particularly
      women, and persons in the 20- to 49-year-old age group. The ALS-associated death
      rate appeared to differ by geographic area, with a higher occurrence among most
      northern states. Our findings suggest that the epidemiology of ALS-associated
      deaths in the United States demonstrated small increases in the overall age
      adjusted death rate and in the death rates among elderly women and adults 20-49
      years of age. Subpopulations at higher risk for ALS were males, whites, persons >
      or =65 years of age, and residents of northern states. This study provides
      information for further studies to examine the epidemiology and risk factors
      associated with ALS.

PMID- 15990446
TI  - Mortality in dementia.
AB  - The objective of this work is to provide a review of the mortality risk in
      dementia and potential influencing factors. In order to do so, studies on
      mortality in dementia based on population-based samples of the last 15 years
      published in PubMed, Web of Science and PSYNDEXplus were considered. Without
      exception, all types of dementia are associated with a considerably increased
      mortality risk. Moreover, the risk of death rises with advancing severity of the
      disorder. Often, a more favorable course of the disease can be found in
      Alzheimer's disease. Further questions, such as the influence of age and sex,
      cannot be answered conclusively. Very little information can be found on aspects
      concerning comorbidity, APOE polymorphism or depressive symptomatology.

PMID- 15990447
TI  - Renal tissue factor expression is increased in streptozotocin-induced diabetic
      mice.
AB  - BACKGROUND: Tissue factor (TF) is the key initiator of the coagulation cascade.
      Recent evidence suggests that TF plays a role in renal fibrin formation and renal
      failure in experimental kidney disease. We hypothesized that hyperglycemia is an
      important stimulus of TF expression in the kidney. METHODS: Mice were injected
      with streptozotocin (STZ) (200 mg/kg) or with control buffer. Three or 10 weeks
      after injection, fibrin, thrombin and TF staining and TF activity were evaluated
      in the kidney. The effect of hyperglycemia on TF expression and secretion by
      tubular epithelial cells was measured in vitro. RESULTS: Kidneys of STZ-treated
      mice showed a marked increase in thrombin staining (3.0 +/- 0.5 vs. 1.2 +/- 0.11)
      (p = 0.002) and an increase in TF clotting activity 10 weeks after STZ injection
      (33.9 +/- 1.3 vs. 25.4 +/- 1.0 s) (p < 0.0001). Increased glomerular fibrin
      deposition was present in 3 out of 6 diabetic mice. Tubular cells incubated with
      D-glucose (25 mmol/l) for 48 h displayed increased cellular TF (p = 0.05).
      However, soluble TF levels and TF activity in supernatant of cells incubated with
      D- or L-glucose were not different. CONCLUSIONS: These data suggest that
      hyperglycemia is a causal factor in procoagulant activity associated with
      diabetic nephropathy.

PMID- 15990448
TI  - Role of the E2F1-p19-p53 pathway in ischemic acute renal failure.
AB  - BACKGROUND: Cell cycle progression and arrest of renal tubular cells after acute
      injury is a reactive process of renal regeneration. The p16(INK4a)/p19(ARF)
      (alternative reading frame) locus encodes two proteins involved in cell cycle
      regulation. We investigated the transcriptional regulation and tissue
      distribution of p19(ARF) in ischemic acute renal failure (ARF). METHODS: We
      examined the time course and immunohistochemistry of p19(ARF) in rat kidneys
      following the induction of ischemic ARF. We also examined the effect of p19(ARF)
      overexpression on p53 levels and cell cycle progression in MDCK cells. RESULTS:
      The protein expression of p19(ARF) strongly increased 72 h after the ischemia.
      Immunohistochemical studies showed that the renal tubular cells in the outer
      medulla expressed p19(ARF) protein 72 h after ischemic injury. The time course of
      E2F1 induction was observed at 6-24 h, and it was found to precede p19(ARF)
      expression. In MDCK cells, the overexpression of E2F1 increased promoter activity
      and the protein level of p19(ARF) and induced apoptosis. Transfection of the
      p19(ARF) expression vector caused an increase in p53 protein, cell cycle arrest
      and apoptosis. CONCLUSIONS: These data support the hypothesis that the E2F1
      p19(ARF)-p53 pathway forms a negative feedback loop to regulate the cell cycle of
      renal tubular cells in the ischemic ARF.

PMID- 15990449
TI  - L-Arginine does not affect renal morphology and cell survival in ischemic acute
      renal failure in rats.
AB  - BACKGROUND: L-Arginine (L-Arg), a substrate of nitric oxide synthases, improves
      renal function in ischemic acute renal failure (iARF). We evaluated whether L-Arg
      improves renal morphology and cell survival in the course of iARF. METHODS AND
      RESULTS: iARF was induced in rats by bilateral clamping of renal arteries for 45
      min. L-Arg was applied intraperitoneally during clamping, and orally during 14
      days of follow-up. Morphology and cell survival of renal cortical and medullar
      tissue was analyzed on days 1, 3, 7, and 14 of follow-up, using toluidine blue
      staining and immunohistochemistry of perfusion-fixated tissue, and Western blot
      analysis of tissue homogenate. Renal tubular injury showed typical features of
      necrosis and was most severe on days 1 and 3 after clamping, predominantly in S3
      segments, with almost complete recovery by day 14. Enhanced medullar monocyte
      infiltration, determined by ED-1 expression as well as by immunohistochemistry,
      and enhanced expression of proliferating cell nuclear antigen (PCNA), indicative
      of proliferation and regeneration, accompanied these morphological changes.
      Compared to controls, L-Arg had no impact on renal morphology, ED-1, and PCNA
      expression. Furthermore, expression of markers of apoptosis Bcl-2, Bax, and
      cleaved caspase-3 was only slightly increased in iARF rats, compared to sham
      operated animals, and was also not influenced by L-Arg. CONCLUSION: Despite its
      repeatedly reported positive impact on renal function as also shown in our model,
      L-Arg does not alter cell death and proliferation in the course of iARF in our
      model. Thus, different mechanisms have to be considered, in particular improved
      intrarenal hemodynamics.

PMID- 15990450
TI  - Mechanisms of the placebo effect and of conditioning.
AB  - A placebo is a sham treatment, such as a pill, liquid, or injection without
      biological activity, used in pharmacology to control for the activity of a drug.
      However, in many cases this placebo induces biological or psychological effects
      in the human. Two theories have been proposed to explain the placebo effect: the
      conditioning theory, which states that the placebo effect is a conditioned
      response, and the mentalistic theory, which sees the patient's expectation as the
      primary cause of the placebo effect. The mechanisms involved in these processes
      are beginning to be understood through new techniques of investigation in
      neuroscience. Dopamine and the endorphins have been clearly shown to be mediators
      of placebo effects. Brain imaging has demonstrated that placebos can mimic the
      effect of the active drugs and activate the same brain areas. This is the case
      for placebo-dopamine in Parkinson's disease, for placebo-analgesics or
      antidepressants, and for placebo-caffeine in the healthy subject. It remains to
      be understood how conditioning and expectation are able to activate memory loops
      in the brain that reproduce the expected biological responses.

PMID- 15990451
TI  - Substance-P-mediated immunomodulation of tumor growth in a murine model.
AB  - BACKGROUND/OBJECTIVE: Substance P (SP) has been reported to have immunoregulatory
      properties including effects on many of the mediators involved in anti-tumor
      immunity. In this study, we investigated the effect of SP on tumor development in
      a murine model of melanoma. In addition, we examined the role of natural killer
      (NK) and T cells in SP-mediated modulation of tumor growth. MATERIALS AND
      METHODS: Mice were implanted with mini-osmotic pumps that delivered a continuous
      infusion of either SP or PBS over a 14-day period. Five days following
      implantation, animals received K1735 melanoma cells and tumor growth was
      monitored. The role of NK and T cells in SP-mediated protection was examined by
      antibody depletion studies. To determine if cells from SP-treated animals could
      delay tumor growth in animals in the absence of exogenous SP infusion,
      splenocytes from mice treated with SP were adoptively transferred into SCID mice.
      RESULTS: In vivoSP treatment led to a significant delay in tumor growth. When
      animals were depleted of NK or T cells, this protective effect was lost. Adoptive
      transfer of cells from SP-treated animals led to a significant protective effect
      on tumor growth in SCID mice. CONCLUSION: Pretreatment of mice with SP provides
      protection against K1735 tumor growth, and this protection requires both T cells
      and NK cells. SP-mediated tumor protection can be transferred by the adoptive
      transfer of cells from SP-treated animals into animals that do not receive
      exogenous SP. These studies suggest a model in which in vivo SP treatment prior
      to tumor challenge primes immune mediators to prevent or delay tumor
      establishment.

PMID- 15990452
TI  - Upregulation of matrix metalloproteinases following nerve injury is not mediated
      by mast cell activation.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) contribute to inflammatory and
      degenerative processes in injured nerves. Since mast cells release mediators
      which upregulate and activate MMPs, we tested the hypothesis that activation of
      mast cells is responsible for changes in the expression and activity of MMP-2 and
      MMP-9 in the injured peripheral nerve. METHODS: The sciatic nerve was partially
      ligated in Wistar rats in which mast cells were stabilized with sodium
      cromoglycate. Expression and activity of MMP-2 and MMP-9 were measured in the
      injured and contralateral nerve using gelatin zymography, and compared between
      mast cell-stabilized and control groups. RESULTS: Expression and activity of MMP
      9 were increased in both the injured and contralateral nerve, but activity of
      MMP2 was slightly reduced by nerve injury. However, stabilization of mast cells
      did not alter the changes in expression or activity of MMP-2 and MMP-9 following
      nerve injury. CONCLUSION: These findings suggest that the contribution of MMP-9
      upregulation to the inflammatory and degenerative changes that follow nerve
      injury is independent of mast cell activation.

PMID- 15990453
TI  - CD30 antigen and multiple sclerosis: CD30, an important costimulatory molecule
      and marker of a regulatory subpopulation of dendritic cells, is involved in the
      maintenance of the physiological balance between TH1/TH2 immune responses and
      tolerance. The role of IFNbeta-1a in the treatment of multiple sclerosis.
AB  - OBJECTIVES: The immunological effect of CD30 on dendritic cells (DCs) was
      examined in a comparative study of patients with relapsing-remitting multiple
      sclerosis (RRMS). The patients were divided into two groups on the basis of
      interferon (IFN)beta-1a treatment: IFNbeta-1a-treated patients and untreated
      patients. We have already shown that CD30 is a marker of cells involved in the
      regulation of the balance between TH1 and TH2 immune responses and so the aim of
      this study was to confirm this role in DCs and, consequently, to clarify the
      immunopathological mechanisms of MS and the causes of immunosuppressive drug
      failure. METHODS: We studied network interactions between soluble (s) CD30 and
      TH1/TH2 cytokines in the supernatants of CD14+-derived immature DC (IDC) and DC
      cultures from treated and untreated patients. Network interactions between the
      sCD30 and cytokines in IDC and DC supernatants were also evaluated in relation to
      TH1/TH2 cytokine serum levels. RESULTS: Our overall results show that CD30 is
      expressed on IDCs and DCs, indicating an immunological role in resting and
      activated physiological conditions. This role would appear to be the regulation
      of the resting and activated physiological balance between the TH1/TH2 immune
      functions as abnormal increases in sCD30 levels result in impaired regulation.
      Further studies are undoubtedly required to clarify this situation. IFNbeta-1a
      treatment was found to determine a fall in sCD30 levels, leading to the
      restoration of the normal functional selection of IDCs from progenitor cells and
      the regulation of the TH1/TH2 network balance. However, IFNbeta-1a treatment may
      also be responsible for the in vivo suppression of CD30-mediated TH1-DC functions
      in immune activation. TH1-DC functions are involved in the induction of T
      regulatory cells for the physiological deletion of self-aggressive cells.
      CONCLUSION: We conclude that CD30 is an important costimulatory molecule and
      marker of a regulatory subpopulation of DCs which induces and modulates immune
      cells involved in the maintenance of the physiological balance between TH1/TH2
      immune responses and tolerance. Elucidating the mechanisms restoring DC and T
      regulatory cell function could lead to more effective therapy and strategies for
      the prevention and treatment of immunopathological conditions such as
      autoimmunity, transplant rejection, allergy and tumors.

PMID- 15990454
TI  - Cultured human adult microglia from different donors display stable cytokine,
      chemokine and growth factor gene profiles but respond differently to a pro
      inflammatory stimulus.
AB  - OBJECTIVES: Brain microglia are highly responsive cells in the central nervous
      system that exert key functions in host defense as well as in neuroprotection and
      regeneration. In this study the gene expression profiles for 268 cytokines,
      chemokines, growth factors and their receptors were examined in cultures of
      purified human adult microglia, using cDNA array profiling. METHODS: Microglia
      from 9 different donors were compared, also following challenge of such microglia
      with the pro-inflammatory cytokines TNF-alpha and IFN-gamma. RESULTS: A stable
      pattern was observed of genes abundantly expressed in the different cultures
      under standard conditions. Genes abundantly expressed in all microglia cultures
      include CCL2 (MCP-1), thymosin beta-10, migration-inhibitory factor-related
      protein 8 (MRP8), MRP14, corticotropin-releasing factor receptor 1 and endothelin
      2. Abundant gene products novel to microglia were neuromodulin (GAP43) and Flt3
      ligand. Yet, treatment with TNF-alpha and IFN-gamma led to widely different
      response profiles among the different cultures. CONCLUSION: These data show a
      surprising level of heterogeneity among human adult microglia cultures in their
      response to a pro-inflammatory stimulus despite the standardized methodology to
      examine this response.

PMID- 15990455
TI  - Oral testosterone in male rats and the development of experimental autoimmune
      encephalomyelitis.
AB  - OBJECTIVES: Considering that sex steroids can influence the immune system, we
      studied the development of experimental autoimmune encephalomyelitis (EAE), a T
      cell-mediated autoimmune disease of the central nervous system, and the
      concomitant cell-mediated immunity in gonadally intact and gonadectomized male
      Wistar rats given testosterone supplementation. METHODS/RESULTS: Sham-operated
      rats and surgically castrated animals were orally self-administered with vehicle
      or testosterone added in the water bottle for 20 days before EAE induction. The
      androgenic effect of oral testosterone self-administration was evidenced by
      changes in body weight, and in the weights of androgen-dependent testes and
      seminal vesicles. Testosterone administration reduced the incidence of clinical
      signs of EAE in sham-operated animals and reversed the clinical symptoms of the
      disease associated with castrated EAE animals. The clinical signs observed in the
      different groups correlated with changes in delayed-type hypersensitivity and
      mononuclear cell-proliferative responses to the encephalitogenic myelin basic
      protein. Moreover, testosterone but not cholesterol supplementation in vitro
      suppressed the proliferative response of mononuclear cells to myelin basic
      protein suggesting that testosterone may affect specific immune functions through
      direct actions on immune cells. Finally, self-administration of testosterone
      induced also elevated corticosterone levels that in sham-operated rats correlated
      with the low incidence of the disease and in gonadectomized animals could be
      involved in the remission of clinical symptoms of EAE. CONCLUSIONS: These results
      suggest that orally self-administered testosterone can modulate specific cellular
      immune responses and serum corticosterone levels leading to changes in the
      development of EAE.

PMID- 15990456
TI  - Promoter polymorphisms of the interferon-alpha receptor gene and development of
      Interferon-induced depressive symptoms in patients with chronic hepatitis C:
      preliminary findings.
AB  - BACKGROUND: Interferon (IFN)-alpha treatment frequently induces depression, which
      can impair quality of life and reduce treatment adherence. Defining relevant risk
      factors for IFN-alpha-induced depression is essential for designing preventative
      treatment strategies. OBJECTIVE: The purpose of the present study was to
      determine whether promoter polymorphisms of -408C/T, -3C/T and GT repeat
      dinucleotide microsatellite in the IFN-alpha/beta receptor 1 (IFNAR1) gene are
      associated with the development of IFN-induced depression. METHOD: Fifty patients
      with chronic hepatitis C were treated with pegylated IFN alpha-2b plus a standard
      or weight-based dose of ribavirin. Severity of depression was assessed using the
      Zung Self-Rating Depression Scale (SDS) at baseline and at 4, 8, 12 and 24 weeks
      of treatment. RESULT: The baseline to maximum difference in the SDS index score
      of neurovegetative/somatic symptoms was higher in patients with the 5/14 genotype
      of the GT repeat dinucleotide microsatellite polymorphism than in those patients
      with other genotypes (p = 0.0084). CONCLUSION: This preliminary result suggests
      that the promoter GT repeat dinucleotide microsatellite polymorphism of the
      IFNAR1 gene may represent a risk factor for the development of depressive
      symptoms during IFN-alpha therapy for hepatitis C and other conditions.

PMID- 15990457
TI  - Alpha-helical CRH exerts CRH agonistic effects on sleep-endocrine activity in
      humans.
AB  - CRH is known to enhance wakefulness and to reduce SWS. In addition, some but not
      all, studies suggest that CRH promotes REM sleep. Alpha-helical CRH exerts CRH
      antagonistic effects in various studies. We studied its effect on sleep EEG and
      nocturnal secretion of ACTH, cortisol, GH (n = 7) in young normal male subjects.
      After administering the substance cortisol and ACTH levels were enhanced during
      the total night compared to placebo. We found an increase of the time spent awake
      for the first half. ACTH (2nd half of the night) and cortisol (total night and
      1st half of the night) increased. The results of the present study correspond to
      a mixture of agonistic and antagonistic effects of alpha-helical CRH.

PMID- 15990458
TI  - Functional polymorphism of the glutathione peroxidase 1 gene is associated with
      personality traits in healthy subjects.
AB  - BACKGROUND: Several lines of evidence suggest that a certain type of personality
      or temperament as well as oxidative stress may be implicated in the
      pathophysiology of neuropsychiatric diseases. Glutathione peroxidase 1 (GPX1)
      plays a role in the antioxidant defense system. OBJECTIVES: The authors studied
      the association between the GPX1 gene polymorphism and personality traits in
      healthy subjects. METHODS: One hundred forty-nine healthy subjects were enrolled.
      Analysis of the functional polymorphism (Pro198Leu) in the human GPX1 gene was
      performed. RESULTS: Subjects with Pro198Pro have significantly higher scores in
      openness to experience on the Revised NEO Personality Inventory (NEO-PI-R) as
      compared with subjects with other genotypes (Pro198Leu or Leu198Leu). In
      contrast, we detected no association between other personality dimensions on the
      NEO-PI-R and scores on the Temperament and Character Inventory. CONCLUSION: This
      study reports that the functional polymorphism (Pro198Leu) in the GPX1 gene might
      be associated with openness to experience among the personality traits.

PMID- 15990459
TI  - Influence of age, gender, health status, and depression on quantitative EEG.
AB  - Quantitative electroencephalography (QEEG) has shown increasing utility in
      assessing brain function in clinical research studies of depression. QEEG
      findings may be influenced by a variety of factors other than the presence of
      depression, including age, gender, depression severity, and physical health
      status. Many of these factors have not been systematically evaluated. We
      therefore examined QEEG measures in 104 subjects with depression and normal
      controls to determine the influence of these factors. We examined QEEG power as
      well as cordance, a QEEG measure that has a stronger association with cerebral
      perfusion than conventional QEEG measures. Prefrontal cordance in the theta band
      has been associated with the pathophysiology of depression and response to
      treatment. We found that prefrontal cordance and relative power in the theta band
      were unaffected by age, gender, severity of depression, and health status, while
      prefrontal absolute power was higher in women than men. All of these measures
      were different from global measures of absolute and relative power, which were
      influenced by age, gender, and health status. These findings suggest that
      prefrontal cordance in depressed patients is not significantly affected by
      factors of age, gender, severity of depression, or physical illness. Global
      measures of power, and to a lesser extent prefrontal absolute power, must be
      interpreted with regard to confounding factors of age, gender, physical illness,
      and severity of depression.

PMID- 15990460
TI  - Association study of a functional MAOA-uVNTR gene polymorphism and cognitive
      function in healthy females.
AB  - Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the degradation
      of dopamine, serotonin and norepinephrine and these neurotransmitters are
      hypothesized to be involved in the cognitive function of humans. This study of a
      cohort of 191 healthy young Chinese females attempts to utilize the intelligence
      quotient (IQ), Wisconsin Card Sorting Test (WCST) and P300 event-related
      potentials as cognitive assessments for testing the relationship between the
      polymorphism with a variable number of tandem repeats (VNTR) in the upstream
      regulatory region (MAOA-uVNTR) and cognition. The results demonstrate that
      subjects bearing the 4/4-repeat genotype have a significantly higher full IQ than
      subjects bearing the 3/3-repeat genotype. However, there is no significant
      association between this MAOA-uVNTR polymorphism and the WCST and P300. Our study
      shows that the MAOA-uVNTR genetic polymorphism plays a role in the IQ; however,
      this may be a chance finding as the result was negative after using the
      Bonferroni adjustment. Therefore, we suggest that our study should be replicated
      and that the testing method, sex, disease and ethnicity should also be considered
      in future studies.

PMID- 15990461
TI  - Vascular endothelial growth factor levels in vitreous and serum of patients with
      either proliferative diabetic retinopathy or proliferative vitreoretinopathy.
AB  - PURPOSES: To confirm the role of vascular endothelial growth factor (VEGF) in the
      pathogenesis of proliferative diabetic retinopathy (PDR) and proliferative
      vitreoretinopathy (PVR) and to investigate the relationship between the level of
      VEGF in serum and its vitreal level in patients with either disease. METHODS:
      Venous blood and vitreous of 18 patients with PDR, 15 patients with PVR and 20
      patients forming a control group were collected during vitrectomy. The VEGF level
      was quantified by using ELISA methods in either serum or vitreous. RESULTS: The
      VEGF level in serum and vitreous was similarly high in the case of PDR, but its
      level was only high in serum in the case of PVR. DISCUSSION: PDR is closely
      linked with systemic diabetes mellitus whereas PVR is more localized. More
      selective systemic anti-VEGF medications with reduced side effects are required
      to treat PDR successfully.

PMID- 15990462
TI  - Inhibitory effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration
      in a human lens epithelial cell line.
AB  - Posterior capsule opacification (PCO) after cataract surgery is caused by growth
      of residual human lens epithelial (HLE) cells on the posterior capsule. We have
      shown that extracellular matrix (ECM) is an essential factor for HLE cell
      attachment and migration. The purpose of this study was to examine the inhibitory
      effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration in an HLE
      cell line. HLE cell line cells (SRA 01/04) that were obtained by transfection of
      large T antigen of SV40 were cultured in the absence of serum. The culture dishes
      were coated with type IV collagen, laminin or fibronectin, and Gly-Arg-Gly-Asp
      Ser-Pro (GRGDSP) RGD peptide (0.1, 0.3, 1.0, 2.0 mg/ml) was added to the medium.
      The number of attached cells was counted after 90 min of incubation, and the
      inhibitory effects of GRGDSP RGD peptide on cell attachment were calculated. Cell
      attachment on the fibronectin-coated dishes was inhibited by GRGDSP RGD peptide
      at concentrations higher than 0.3 mg/ml; the inhibitory rate was 80% at a
      concentration of 2.0 mg/ml. The inhibition of cell attachment by GRGDSP RGD
      peptide on laminin-coated dishes appeared only at a concentration of 2.0 mg/ml,
      whereas no effects were observed on the type IV collagen-coated dishes. The
      inhibitory effects of GRGDSP RGD peptide on cell migration were measured in
      medium containing 2.0 mg/ml of GRGDSP RGD peptide after 1, 3, 5 and 7 days of
      culture. Cell migration was inhibited by GRGDSP RGD peptide from 1 day of culture
      on the fibronectin-coated dishes and from 5 days of culture on the laminin-coated
      dishes, whereas no effects were observed on the type IV collagen-coated dishes.
      GRGDSP RGD peptide inhibited cell attachment and migration on laminin and
      fibronectin that have RGD sequences. These data suggested that RGD peptide may
      have the potential to prevent PCO.

PMID- 15990463
TI  - The effect of exposure time on maximum acceptable dose for avoidance of
      ultraviolet radiation-induced cataract.
AB  - The effect of exposure time on maximum acceptable dose (MAD) for avoidance of
      ultraviolet radiation B (UVRB)-induced cataract was investigated. Sprague-Dawley
      rats were divided into 5 exposure time groups: 7.5, 15, 30, 60, and 120 min. Each
      exposure time group was divided into 5 dose subgroups: 0, 1, 2, 4, and 8 kJ/m2.
      The rats were unilaterally exposed to UVR around 300 nm. One week after the
      exposure, macroscopic structure was recorded and lens forward light scattering
      was measured. MAD for avoidance of UVRB-induced cataract was estimated based on
      the dose-response function. MAD for avoidance of UVRB-induced cataract for 7.5,
      15, 30, 60, and 120 min exposures was estimated to be 2.0, 1.4, 1.9, 1.8 and 2.2
      kJ/m2, respectively. In the exposure time domain 7.5-120 min, MAD for avoidance
      of UVRB-induced cataract depends on exposure time.

PMID- 15990464
TI  - Minocycline partially inhibits caspase-3 activation and photoreceptor
      degeneration after photic injury.
AB  - PURPOSE: To evaluate the possible role of caspase-3 in retinal photic injury, and
      to investigate whether minocycline can ameliorate light-induced photoreceptor
      degeneration. METHODS: Retinal photic injury was induced in rats by exposure to
      intense light. Expression of caspase-3 was studied using Western blot analysis,
      immunohistochemical staining and enzyme activity assay. Apoptotic photoreceptor
      cells were detected by the TdT-dUTP terminal nick-end labeling (TUNEL) method.
      Minocycline (15, 30 or 45 mg/kg) was administered before or after photic injury
      in rats randomly assigned to pretreatment and posttreatment groups. Minocycline
      and vehicle-treated retinas subjected to photic injury were compared with respect
      to Western blotting, enzyme activity assay, quantitative counts of TUNEL stains,
      morphometry of the outer nuclear layer (ONL) thickness and histopathological
      examination. RESULTS: After light exposure, active caspase-3 and poly-adenosine
      diphosphate-ribose-polymerase were upregulated in the retinas and increased
      caspase-3 immunoreactivity was observed in the ONL. Caspase-3 enzyme activity
      increased in the retinas that underwent photic injury, and this increase was
      significantly reduced in minocycline pretreated (30 and 45 mg/kg) and posttreated
      (45 mg/kg) groups. Intraperitoneal administration of minocycline before or after
      photic injury in rats also resulted in less TUNEL-positive photoreceptors, as
      assessed by the quantitative TUNEL counts. The degree of retinal degeneration,
      measured by the ONL thickness 14 days after photic injury, was significantly
      improved in minocycline pretreatment (45 mg/kg) rats. CONCLUSIONS: We demonstrate
      that increased caspase-3 activities localize specifically within the ONL after
      photic injury, and that minocycline partially inhibits caspase-3 activation and
      photoreceptor degeneration in this animal model.

PMID- 15990465
TI  - Quantification of pharyngeal patency in patients with sleep-disordered breathing.
AB  - Many techniques are available for the assessment of pharyngeal characteristics in
      sleep-disordered breathing (SDB). However, most of the reported techniques are
      invasive to some extent and/or hard to perform during sleep studies. The focus of
      this concept paper is on the forced oscillation technique (FOT) to quantify
      pharyngeal patency in patients with SDB. In a pilot study, the potential of FOT
      for non-invasive and continuous assessment of pharyngeal patency during different
      types of respiratory events was studied in 8 patients with an established
      diagnosis of a sleep apnea-hypopnea syndrome. During polysomnography, FOT was
      applied using a 5-Hz pressure oscillation signal. The respiratory impedance was
      determined and considered as a marker for pharyngeal patency. The results
      demonstrate that FOT allows detection of the complete pharyngeal occlusion during
      obstructive sleep apnea. In addition, we found that central sleep apnea can be
      associated with pharyngeal closure. We also demonstrated that during the flow
      limited breath preceding obstructive apnea, almost complete upper airway closure
      can occur during either the expiratory or the inspiratory phase. FOT is a
      suitable method to assess pharyngeal patency continuously and non-invasively
      during sleep. Furthermore, this technique has the potential to contribute
      substantially to our knowledge of upper airway physiology in SDB.

PMID- 15990466
TI  - Superior semicircular canal dehiscence: a series of 13 cases.
AB  - Increasingly more detailed imaging techniques have recently highlighted the
      frequent occurrence of bony labyrinthine dehiscence. Among them, superior canal
      dehiscence (SCD) has been described in a number of cases presenting different
      features. Here, we report a series of 13 cases, in which the detection of
      vestibular evoked myogenic potentials (VEMPs) in response to stimuli of
      abnormally low intensity as compared to normal responses led us to suspect the
      presence of a 'third window effect'. An accurate HRCT investigation allowed the
      diagnosis of SCD. Anamnestic and symptomatologic differences seem difficult to
      explain, although in our opinion a dural rupture could be at the basis of the
      onset of pathologic manifestations after many years of silence of a probably
      malformative condition.

PMID- 15990467
TI  - Improved capsulotomy for refractory Tourette's syndrome.
AB  - The effects of bilateral anterior capsulotomy were analyzed in 12 patients with
      Tourette's syndrome (TS). All of the patients underwent bilateral anterior
      capsulotomy. In 7 patients, the target was the anterior one third of the anterior
      limb of the capsula interna, while in 5 patients, the posterior one third of this
      structure was targeted. Radiofrequency thermolesions were created at 80 degrees C
      for 60 s. These surgeries resulted in a reduction in TS symptoms (motor and vocal
      tics and/or obsessive-compulsive behavior) of >50% in all patients, regardless of
      the target. A comparison of the two lesion sites suggests that patients with
      lesions of the posterior one third of the anterior limb have a greater reduction
      in TS symptoms (>80%) than patients receiving lesions of the anterior one third
      of the anterior limb (>50%). No severe, permanent side effects were observed in
      any patient.

PMID- 15990468
TI  - Antiepileptic effects of repetitive transcranial magnetic stimulation in patients
      with cortical malformations: an EEG and clinical study.
AB  - OBJECTIVE: To study the effects of repetitive transcranial magnetic stimulation
      (rTMS) on epileptic EEG discharges in patients with refractory epilepsy and
      malformations of cortical development (MCDs). METHODS: Eight patients with MCD
      and refractory epilepsy underwent 1 session of low-frequency rTMS (0.5 Hz, 600
      pulses) focally targeting the MCD. The number of epileptiform discharges (EDs) in
      the EEG and seizures were measured before (baseline), immediately after as well
      as 15 and 30 days after rTMS treatment. RESULTS: Stimulation significantly
      decreased the number of EDs 15 and 30 days after rTMS treatment (mean reduction
      of 46.4%, 95% CI 12.7-80.2%, and mean reduction of 42.1%, 95% CI 8.2-75.7%,
      respectively). This was associated with a significant reduction in the number of
      seizures reported as compared with the 4-week period preceding rTMS (mean
      reduction of 57.3%, 95% CI 33.1-80.3%, and mean reduction of 51.2%, 95% CI 27.9
      74.9%, respectively). CONCLUSION: This open study shows a significant
      antiepileptic effect of rTMS based on clinical and electrophysiological criteria
      and supports the therapeutic utility of rTMS for patients with well-localized
      epileptogenic cortical malformations.

PMID- 15990469
TI  - Stimulation of the posterior hypothalamus for medically intractable impulsive and
      violent behavior.
AB  - OBJECTIVE: To describe the therapeutic effect of deep brain stimulation for the
      treatment of patients with below-average IQs who are affected by aggressive and
      disruptive behavior and who are resistant to any drug and/or conservative
      treatment (including occupational therapy). PATIENTS AND METHODS: Two consecutive
      patients suffering from mental retardation with aggressive and disruptive
      behavior and resistant to any pharmacological treatment underwent deep brain
      stimulation electrode placement in the posteromedial hypothalamus for continuous
      chronic high-frequency stimulation (HFS). The stereotactic coordinates of the
      target were chosen according to the study by Sano et al., which involved
      hypothalamic stereotactic lesions. RESULTS: HFS of the posteromedial hypothalamus
      demonstrated consistent improvement of disruptive behavior in both patients at
      the follow-up evaluation 1 year later. CONCLUSIONS: HFS of the posteromedial
      hypothalamus showed similar results to those obtained by Sano et al. in the 1960s
      with radiofrequency lesions of the same target volume. The reversibility of
      neurostimulation allows HFS to control disruptive behavior when conservative
      treatments are ineffective, and drug therapy is uneventful or causes severe side
      effects. In conclusion, this neuromodulation procedure improved the quality of
      life and the range of social relationships for both of the treated patients.

PMID- 15990470
TI  - A preliminary study of transient confusional states following bilateral
      subthalamic stimulation for Parkinson's disease.
AB  - Transient postoperative confusion (POC) occurs in 5-25% of patients following
      bilateral subthalamic nucleus stimulation. We retrospectively reviewed data on 96
      patients who underwent bilateral subthalamic nucleus deep brain stimulation for
      Parkinson's disease. Nine percent of patients developed POC. There was no
      significant correlation between age/perioperative factors and POC. The POC group
      had a significantly higher incidence of depression and frontal-subcortical
      dysfunction on preoperative evaluation than patients without POC. Postoperative
      neuropsychological evaluations revealed declines on measures of general cognitive
      function and memory in the POC group. We provide preliminary evidence that
      patients with depression and frontal-subcortical dysfunction are more likely to
      develop POC, and that POC is more often associated with cognitive decline
      following surgery.

PMID- 15990471
TI  - Obsessive-compulsive disorder: an overview.
AB  - In this article, which is the first in a three-part series, the authors provide
      an overview of the current state of our knowledge of the phenomenology, etiology,
      and diagnosis of OCD. The DSM-IV criteria for OCD are presented and explicated.
      Disorders that are commonly comorbid with OCD (e.g., major depressive disorder,
      other anxiety dis-orders, Tourette's disorder) are described. The authors also
      discuss disorders such as body dysmorphic disorder that may be related to OCD and
      are often termed OCD spectrum disorders. OCD is likely to have multiple causes
      and the authors discuss behavioral, neuroanatomical, and neurochemical theories
      of OCD. Two treatments have demonstrated efficacy in OCD, cognitive-behavioral
      therapy and pharmacotherapy with serotonergic reuptake inhibitors, and the
      authors discuss how these treatments may work in light of what is known about the
      etiology of the disorder. The different subtypes of OCD that have been proposed
      are described along with their implications for treatment. The article concludes
      with a discussion of diagnosis that provides specific guidance for the clinician
      on how to assess a patient for possible OCD. The next two articles in this series
      will cover cognitive-behavioral and medication treatment in detail.

PMID- 15990473
TI  - Psychotherapy with women survivors of sexual abuse.
AB  - The essential elements of psychotherapy with women who were sexually abused in
      childhood are outlined. The author begins with a brief discussion of the
      prevalence and impact of childhood sexual abuse. She reviews the assessment of
      patients who may have been the victims of such abuse and then describes the three
      stages of treatment for such patients. The article concludes with a discussion of
      the importance of considering issues of transference and countertransference in
      providing psychotherapy to women survivors of sexual abuse.

PMID- 15990472
TI  - Self-help and guided self-help treatments for bulimia nervosa and binge eating
      disorder.
AB  - This article reviews the use of self-help and guided self-help treatments for
      bulimia nervosa (BN) and binge eating disorder (BED). Available data suggest that
      self-help and guided self-help treatments based on empirically-supported
      cognitive behavioral therapies (CBT) have efficacy for binge eating problems.
      Emerging findings from initial studies suggest that the magnitude of the
      differences in outcomes between certain guided-self-help CBT programs and
      therapist-led CBT may not be substantial, although further research is clearly
      indicated. Initial data suggest that self-help and guided self-help CBT programs
      may not only demonstrate "efficacy" but also "effectiveness"-i.e., utility in
      "real-world" primary care or community settings. Implications for clinical
      practice and for future research are discussed.

PMID- 15990474
TI  - Successful cerebral aging: clinical and pharmacological approaches to the aging
      brain.
AB  - The author first defines what he means by "successful cerebral aging." He then
      discusses how major depression and dementia can interfere with this process and
      describes how what he terms "chronic stress dysphoria" can contribute to neuronal
      damage and mental impairment. The author then reviews a number of types of
      chronic stress, including health problems, loneliness, loss of autonomy,
      inactivity, and low self-esteem, and suggests possible solutions for minimizing
      their effect on successful aging.

PMID- 15990475
TI  - Understanding family, community, immigration, and acculturation issues in
      psychodynamic psychotherapy with Asian Americans.
AB  - The authors discuss the importance of issues related to family, community,
      immigration, and acculturation in providing psychodynamic psychotherapy for Asian
      Americans. Despite differences between specific sub-ethnic groups of Asian
      Americans, many of these groups share an emphasis on group connectedness and
      family unity that can have important implications for individual development and
      can influence the course of psychotherapy with these patients. The authors first
      review the effects of immigration and dislocation (e.g., culture shock, mourning
      for the loss of family, friends, and familiar cultural environment) on Asian
      Americans, and then describe the types of changes and stresses the acculturation
      process can produce. These include guilt at leaving family behind in the country
      of origin and intergenerational conflict between parents and their more
      Westernized children, especially concerning social life, dating, and marriage.
      The authors then use Asian Indian family structure and community life to
      illustrate the types of effects family organization and roles and community
      context have on Asian American individuals. In the second half of the article,
      the authors discuss how these cultural factors can influence the process of
      psychotherapy and describe techniques that may improve the chances of successful
      therapy (e.g., being sensitive to patients' reluctance to discuss personal issues
      outside the family, being more willing to involve family members in the therapy
      process).

PMID- 15990476
TI  - Using principles of ACT to integrate community care for people with mental
      retardation and mental illness.
AB  - The authors describe the use of an Assertive Community Treatment (ACT) approach
      in a community living program for persons with both mental retardation and mental
      illness. The development of the program occurred in the context of a statewide
      project to serve more than 1,000 dually diagnosed persons who were members of a
      class action lawsuit against the State of North Carolina. The use of ACT
      principles marked a substantive departure from the residential supervision and
      brokered service model employed for the Class throughout the State. The authors
      describe the public policy context within which the program was developed,
      discuss the rationale for selecting the ACT model, describe its implementation,
      and summarize service utilization and outcome information. Changes by the funding
      agency in its expectations of program staffing and reimbursement methodology that
      were made after the program was approved led to its early demise. Although the
      program lasted less than 2 years, during its tenure most participants realized
      marked improvement in symptoms and community adjustment. Results may cautiously
      be interpreted as indicating that ACT may reduce the reliance on 24-hour
      residential and community supervision for many persons with both mental
      retardation and mental illness.

PMID- 15990477
TI  - A comparison of the Kennedy Axis V and the Global Assessment of Functioning
      Scale.
AB  - In this article, the authors evaluate two brief clinician-scored global
      assessment instruments used to measure the functioning of adult clients who have
      a serious mental illness: the Global Assessment of Functioning (GAF) Scale and
      the relatively new Kennedy Axis V (K Axis). Although both instruments are brief
      and easy to score, the K Axis provides a multi-dimensional evaluation, while the
      GAF provides a single, unidimensional picture of a client's functioning.
      Statistical analyses indicated that both instruments have adequate validity and
      reliability if the clinicians using them are sufficiently trained. Correlations
      between the two instruments were high where expected. Statistically significant
      differential functioning was found for various subgroups. The K Axis was better
      able to pinpoint this specific differential functioning.

PMID- 15990478
TI  - Can the patient-physician relationship survive in the era of managed care?
AB  - The author discusses the history of the patient-physician relationship and
      considers how recent developments in the health care system have affected the
      viability of that relationship. He first considers the justification for
      maintaining such a relationship and concludes that the patient-physician
      relationship must be preserved because it has a long history, is humane and
      ethical, and is cost effective. The author then reviews the ethical basis that
      forms the foundation of the patient-physician relationship. He discusses issues
      related to competency, commitment, compassion, equanimity, and patient advocacy.
      The article concludes with a consideration of the medical-ethical dilemmas
      created in the patient-physician relationship by managed care.

PMID- 15990479
TI  - Biological therapies for obsessive-compulsive disorder.
AB  - Two treatments have demonstrated efficacy in OCD, exposure and response (ritual)
      prevention (EX/RP) and pharmacotherapy with serotonin reuptake inhibitors (SRIs).
      In this article, which is the third in a three-part series, the authors present
      an overview of the role of biological treatments for OCD. The evidence for the
      efficacy of the serotonin reuptake inhibitors (clomipramine and the five
      selective serotonin reuptake inhibitors "SSRIs" fluvoxamine, fluoxetine,
      paroxetine, sertraline, and citalopram) as monotherapy for OCD is reviewed. The
      authors also discuss the rationale for choosing among these agents for specific
      patients. Research on other types of medication monotherapies for OCD is also
      discussed. The authors then cover strategies for treatment-resistant OCD,
      including combining EX/RP and SRI medication treatment, combining clomipramine
      and an SSRI, use of augmenting medications, and use of intravenous clomipramine.
      Findings concerning the use of other somatic therapies for treatment-resistant
      OCD, including electroconvulsive therapy, neurosurgery, plasma exchange/IV
      immunoglobulin/maintenance antibiotics, and transcranial magnetic stimulation,
      are also reviewed. Finally, the authors discuss what is known about matching
      treatments to patients with certain specific symptom clusters, how long to
      continue maintenance medication treatment, and how to terminate treatment.

PMID- 15990480
TI  - Psychiatric considerations in the diagnosis, treatment, and prevention of
      HIV/AIDS.
AB  - HIV/AIDS has the unfortunate distinction of being one of the most devastating
      epidemics of the twentieth century. By the end of June, 1999, 420,201 deaths in
      persons with AIDS had been reported in the United States. While HIV/AIDS patients
      are currently living longer as a result of more effective and complex treatments,
      no vaccination or cure has yet been discovered. Over the years, the HIV/AIDS
      epidemic has become multifactorial and currently affects several different
      special population groups. Individuals who are at high risk for becoming infected
      with HIV or who already suffer from HIV/AIDS can benefit greatly from the
      interventions of psychiatrists or other mental health professionals. It is
      important that psychiatrists collaborate very closely with infectious disease
      specialists in the management of HIV/AIDS and its psychological sequelae. The
      authors describe the psychiatric conditions that most often occur in association
      with HIV/AIDS: mood disorders, anxiety disorders, substance-related disorders,
      psychotic disorders, insomnia and sleep disorders, delirium, dementia, and pain
      syndromes. We present guidelines for diagnosis and psychopharmacological and
      psychotherapeutic treatment of these disorders in patients with HIV/AIDS. The
      article concludes with a discussion of prevention strategies that can be used in
      a mental health treatment setting and special issues related to treating HIV/AIDS
      in certain special population groups.

PMID- 15990481
TI  - Long-term treatment of panic disorder with agoraphobia in private practice.
AB  - The author followed 67 patients with panic disorder with agoraphobia (PDA) for a
      minimum of 5 years in a private practice setting. They were treated with a
      combination of pharmacotherapy (antidepressants or benzodiazepines) and cognitive
      behavioral psychotherapy. The author examines outcomes for three groups: A) 11
      male patients, 10 of whom had comorbid conditions; B) 21 female patients with
      comorbid conditions; and C) 35 female patients without comorbid conditions.
      Symptom severity was assessed using the Panic Disorder Severity Scale (PDSS).
      Patients in all groups showed marked improvement in all the domains measured by
      the PDSS, with the greatest improvement in PDSS scores occurring during the first
      year in all three groups. Patients in groups A and B tended to plateau after 5
      years of treatment and show no additional improvement thereafter, whereas
      patients in group C (women with "pure PDA") continued to improve, although at a
      gradually slower rate. However, after an average of 11 years of treatment, the
      majority of patients remained symptomatic. The presence of comorbid alcohol abuse
      or depression was associated with poorer outcomes. The results in this
      effectiveness study are generally not as good as the outcomes of published PDA
      follow-up efficacy studies, but appear to be superior to outcomes in cohorts of
      chronically anxious patients treated decades ago.

PMID- 15990482
TI  - The primacy of early experience: a critique, an alternative, and some clinical
      implications.
AB  - The author critically examines the concept that early childhood experience plays
      a centrally important role in psychological development. This principle is
      contradicted by a wide range of evidence, most particularly that the cumulative
      effect of adverse experiences is more important than timing, and that children
      are resilient to a wide range of adverse events. An alternative model is offered,
      rooted in the interactions between temperament and childhood experiences. Some
      clinical implications of the model are also explored.

PMID- 15990483
TI  - Childhood obsessive-compulsive disorder: a review.
AB  - Obsessive-compulsive disorder (OCD) holds a particular interest for child
      psychiatrists because of the high proportion of cases with onset in childhood and
      adolescence. Over the last two decades, substantial progress has been made in
      describing OCD in children and adolescents and in developing and implementing
      effective treatments. In addition, research on the phenomenology, neurobiology,
      and psychopharmacology of OCD has led to its current conceptualization as a
      developmental neuropsychiatric disorder. In this article, the fourth in a series
      on OCD, the authors summarize the most recent data on the phenomenology,
      etiology, neurobiology, and treatment of OCD in children and adolescents.

PMID- 15990484
TI  - Neurocognition as a determinant of employment status in schizophrenia.
AB  - Chronic unemployment is a major problem faced by many persons with schizophrenia.
      In this article, the author first reviews reasons why employment is an important
      goal for patients with schizophrenia. Employment appears to improve the clinical
      symptoms of schizophrenia. Employment also reduces the economic costs of the
      illness to society. The author then discusses predictors of positive employment
      outcomes in schizophrenia. Clinical symptoms, especially positive symptoms, do
      not appear to play a large role in predicting occupational functioning in
      schizophrenia. The author than reviews the evidence for the role of cognitive
      impairment in unemployment in patients with schizophrenia. In seven of the eight
      studies reviewed, significant relationships between cognitive functioning and
      work status/work behaviors were reported. These studies provide the basis for
      identifying those patients most at risk for the poorest occupational outcomes as
      well as those most likely to benefit from focused intervention.

PMID- 15990485
TI  - Medication treatment of bipolar disorder 2000: a summary of the expert consensus
      guidelines.
AB  - The original Expert Consensus Guidelines on the Treatment of Bipolar Disorder
      were published in 1996. Since that time, a variety of new treatments for bipolar
      disorder have been reported; however, evidence for these treatments varies
      widely, with data especially limited regarding comparisons between treatments and
      how to sequence them. For this reason, a new survey of expert opinion was
      undertaken to bridge gaps between the research evidence and key clinical
      decisions. The results of this new survey, which was completed by 58 experts, are
      presented in The Expert Consensus Guideline Series: Medication Treatment of
      Bipolar Disorder 2000, which was published in April 2000 as a Postgraduate
      Medicine Special Report. In this article, the authors describe the methodology
      used in the survey and summarize the clinical recommendations given in the
      resulting guidelines. The expert panel reached consensus on many key strategies,
      including acute and preventive treatment of mania (euphoric, mixed, and dysphoric
      subtypes), depression, rapid cycling, and approaches to managing treatment
      resistance and comorbid psychiatric conditions. Use of a mood stabilizer is
      recommended in all phases of treatment. Divalproex (especially for mixed or
      dysphoric subtypes) and lithium are the primary mood stabilizers for both acute
      and preventive treatment of mania. If monotherapy with these agents fails, the
      next recommended intervention is to combine them. This combination of lithium and
      divalproex can then serve as the foundation to which other medications are added
      if needed. Carbamazepine is the leading alternative mood stabilizer for mania.
      The experts rated the other new anticonvulsants as second-line options (i.e.,
      their use is recommended if lithium, divalproex, and carbamazepine fail or are
      contraindicated). For milder depression, a mood stabilizer, especially lithium,
      may be used as monotherapy. Divalproex and lamotrigine are other first-line
      choices. For more severe depression, the experts recommend combining a standard
      antidepressant with lithium or divalproex. Bupropion, selective serotonin
      reuptake inhibitors (SSRIs), and venlafaxine are preferred antidepressants. The
      antidepressants should usually be tapered 2-6 months after remission. Monotherapy
      with divalproex is recommended for the initial treatment of either depression or
      mania in rapid-cycling bipolar disorder. Antipsychotics are recommended for use
      in combination with the above regimens for mania or depression with psychosis,
      and as potential adjuncts in nonpsychotic episodes. Atypical antipsychotics,
      especially olanzapine and risperidone, were generally preferred over conventional
      antipsychotics. The guidelines also include recommendations concerning the use of
      electroconvulsive therapy (ECT), clozapine, thyroid hormone, stimulants, and
      various novel agents for patients with treatment-refractory bipolar illness. The
      experts reached high levels of consensus on key steps in treating bipolar
      disorder despite obvious gaps in high-quality data. To evaluate many of the
      treatment options in this survey, the experts had to extrapolate beyond
      controlled data; however, their recommendations are generally conservative.
      Experts give their strongest support to initial strategies and medications for
      which high-quality research data or longstanding patterns of clinical usage
      exist. Within the limits of expert opinion and with the understanding that new
      research data may take precedence, these guidelines provide clear pathways for
      addressing common clinical questions and can be used to inform clinicians and
      educate patients about the relative merits of a variety of interventions.

PMID- 15990486
TI  - Pentavalent treatment: preliminary effects on state hospital utilization.
AB  - The purpose of this exploratory study was to determine if a low-cost alternative
      to assertive community treatment (ACT) programs could achieve results comparable
      to those previously reported by high-fidelity ACT programs with regard to state
      hospital utilization by patients with long-term, treatment-refractory serious
      mental illness and high rates of hospital recidivism. A sample of 30 patients was
      exposed to a low- cost alternative to ACT for a 12-month period. A quasi
      experimental research design was used to compare state hospital utilization by
      the treatment group and a matched comparison group. The treatment group exhibited
      significantly less state hospital utilization than the comparison group and had
      an 88% reduction in state hospital utilization in comparison to its 10-year
      baseline. Low cost alternatives to ACT programs may be as effective as high
      fidelity programs in reducing state hospital utilization and may be more easily
      adaptable to the current structure, operation, and financial constraints of
      community mental health centers.

PMID- 15990487
TI  - Computerizing medication algorithms and decision support systems for major
      psychiatric disorders.
AB  - In this article, the authors discuss the rationale for the use of computerized
      medication algorithms and decision support systems in the treatment of major
      psychiatric disorders. The field of psychopharmacology has advanced tremendously
      in the last two decades, with the resulting vast array of new information
      yielding a marked disparity between actual practice and what is commonly called
      "best practice." As a remedy, clinical practice guidelines and algorithms have
      been widely developed. These algorithms are used to disseminate up-to-date
      information, effect change in physician behavior, and reduce untoward variation
      in care. Review of the literature reveals advantages and limitations in trying to
      implement these paper and pencil guidelines and algorithms. Available research
      also suggests that computerized decision support systems have the potential to
      overcome such limitations, increase the use of treatment guidelines and
      algorithms, and improve physician adherence to recommended practices. The
      advantages of computerized medication algorithms and decision support systems are
      discussed. Finally, the computer platform elements that are necessary to make
      such systems effective and user-friendly are described.

PMID- 15990488
TI  - Modeling the relationship between affective lability, impulsivity, and suicidal
      behavior in patients with borderline personality disorder.
AB  - This article reviews the concept of affective lability and suggests that new
      models are needed to characterize the relationship between affective states such
      as affective lability, impulsivity, and suicidal behavior. The association of
      affective lability, impulsivity, and suicidal behavior is most relevant to
      understanding the risk of suicide in individuals with borderline personality
      disorder. The relationship between affective lability and suicide might be
      explained as 1) a form of bipolarity, 2) a form of impulse dyscontrol, 3) a
      quantitative disorder of affect, or 4) an environmental reactivity. Our opinion
      of the relevant literature suggests that a quantitative disorder of affect
      accompanied by the inability to control these affects are the essential
      components leading to the risk of suicidal behavior. Characterizing the
      dyscontrol and high intensity of affect leads to a reconceptualization of
      depression in patients with borderline personality disorder and to a re
      examination of the causal chain of events leading to suicidal behavior. The
      implications for clinical practice resulting from the proposed model are
      discussed.

PMID- 15990489
TI  - When acute-stage psychosis and substance use co-occur: differentiating substance
      induced and primary psychotic disorders.
AB  - Substances such as alcohol, cocaine, amphetamine, and cannabis can produce
      psychotic reactions in individuals who are otherwise free of serious mental
      illness. However, persons with primary psychotic disorders, such as schizophrenia
      and bipolar disorder, who use these substances often present for treatment with
      signs and symptoms similar to those whose psychosis resulted from the use of
      drugs alone. While it is often difficult to distinguish substance-induced from
      primary psychoses, especially early in the course of treatment, this differential
      diagnosis has important implications for treatment planning. To help clinicians
      distinguish these two types of presentations, the authors first review the types
      of psychotic symptoms that can co-occur with substance use. They discuss the
      prevalence and patterns of substance use that have been found in patients with
      schizophrenia and other primary psychotic disorders and review the negative
      outcomes associated with substance use in this population. The prevalence of and
      types of symptoms and problems associated with psychotic symptoms that occur as a
      result of substance use alone are also reviewed. The authors describe assessment
      procedures for differentiating substance-induced and primary psychotic disorders.
      They stress the importance of accurately establishing the temporal relationship
      between the substance use and the onset and continuation of psychotic symptoms in
      making a differential diagnosis, as well as the importance of being familiar with
      the types of psychological symptoms that can occur with specific substances. The
      authors review the utility and limitations of a number of diagnostic instruments
      for assessing patients with co-occurring psychosis and substance use problems,
      including The Addiction Severity Index, The Michigan Alcohol Screening Test, and
      diagnostic interviews such as the Schedule for Affective Disorders and
      Schizophrenia and the Structured Clinical Interview for DSM. They then discuss
      the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), an
      instrument that has been developed to address the lack of a diagnostic interview
      that is suitable for assessing the comorbidity of substance use and psychiatric
      disorders. The article concludes with a discussion of the importance of an
      appropriate match between diagnosis and treatment and the current state of our
      knowledge concerning the most appropriate types of treatment interventions for
      patients with substance-induced psychosis and those with dual diagnoses.

PMID- 15990490
TI  - Mastering the cytochromes: a practical primer.
AB  - The author reviews the basic properties of the cytochrome enzyme systems and
      discusses why it is important for prescribing psychiatrists to be familiar with
      them. He then reviews the specific properties and types of interactions
      associated with the cytochrome families that play the most important roles in
      psychotropic drug metabolism: CYP 3A4, CYP 2D6, CYP 1A2, and CYP 2C. Tables are
      provided listing the principle substrates, inhibitors, and inducers of each of
      these cytochrome families. Finally, practical and clinical considerations in
      assessing the potential for cytochrome interactions are reviewed and illustrated
      with clinical vignettes.

PMID- 15990491
TI  - Long-term adverse effects of novel antipsychotics.
AB  - The introduction of novel antipsychotics for the treatment of patients with
      serious psychiatric illness has alleviated the burden of managing some of the
      side effects of conventional agents. However, the novel agents may also cause
      adverse events. The long-term adverse events of concern include weight gain,
      diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia.
      Recent studies with the novel agents have prompted clinicians to revisit
      antipsychotic-induced weight gain. Clinically significant weight gain puts
      patients at risk for coronary heart disease, hypertension, type II diabetes,
      dyslipidemia, and some types of cancer. More recently, case reports of glucose
      abnormalities and diabetes have emerged, indicating that some novel
      antipsychotics may be associated with altered glucose metabolism or insulin
      sensitivity. The novel antipsychotics may also have a lower propensity for
      causing TD than the conventional antipsychotics. Side effects associated with
      hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual
      dysfunction. All of these adverse events can cause patients to become non
      compliant and may thus predispose them to relapse. In this review, the authors
      summarize the literature on the long-term side effects of the novel
      antipsychotics and examine the severity of the problem, with recommendations for
      management. When selecting treatments, clinicians should consider the side-effect
      profiles of the various antipsychotic agents.

PMID- 15990492
TI  - Clinical research on antipsychotics in bipolar disorder.
AB  - Antipsychotics are commonly used in bipolar disorder, both for acute mania and in
      maintenance treatment. The authors review available clinical research concerning
      the use of both conventional and atypical antipsychotics in bipolar disorder and
      present recommendations for a number of key clinical situations based on this
      review. They also consider a number of important related questions, including
      whether there is evidence for an increased risk of tardive dyskinesia (TD) in
      patients with bipolar disorder, the potential role for antipsychotics in the
      treatment of bipolar depression, the role of antipsychotics in maintenance
      treatment of bipolar disorder, the potential for antipsychotics to induce
      depression in bipolar illness, and whether antipsychotics can be considered mood
      stabilizers with a place as monotherapy for bipolar mania. They conclude that
      standard treatment for acute mania should begin with a mood stabilizer, with
      benzodiazepines used as an adjunct for mild agitation or insomnia and
      antipsychotics used as an adjunct for highly agitated, psychotic, or severely
      manic patients. They also conclude that atypical antipsychotics are preferable to
      conventional antispychotics because of their more favorable side effect profile
      and reduced risk of tardive dyskinesia. They review the evidence for using
      atypical antipsychotics as first-line monotherapy for mania and conclude that
      more evidence concerning the risk of TD and their efficacy as maintenance
      treatment in bipolar disorder is needed before a conclusion can be made. Should
      the eventual risk of TD associated with atypical antipsychotics be found to be
      minimal and their efficacy in maintenance treatment found to be high, they could
      eventually be considered first line monotherapy for bipolar disorder. They
      conclude that treatment with an antipsychotic during bipolar depression should be
      limited to those patients who have psychosis and that atypical antipsychotics are
      preferred over conventional antipsychotics in this situation, not only because of
      their reduced risk of side effects but also because theoretically they may have
      antidepressant efficacy due to their effects on the serotonin system. The
      clinical research findings summarized in the article are, for the most part,
      supported by a recently published guideline based on a consensus of clinical
      experts.

PMID- 15990493
TI  - Neurogenesis and depression.
AB  - The recognition that the brain continues to generate new neurons well into
      adulthood has made a marked impact on the field of neuroscience in general and
      specifically on neurobiological models of the pathogenesis of major depression.
      Stress, neuroendocrine activation, neurotransmitter systems, and other factors
      can down-regulate the process of neurogenesis and may contribute to certain
      morphological changes seen in depression. Evidence is emerging that
      antidepressant treatments may mitigate these effects by stimulating neurogenesis
      in particular regions of the brain. This review introduces the reader to recent
      literature on neurogenesis as it relates to the understanding and treatment of
      depression.

PMID- 15990494
TI  - Termination of psychotherapy: a training perspective.
AB  - Given the constraints of the prevailing mental health system in the United
      States, it has become very challenging for psychiatrists to offer psychotherapy
      services to patients in need of this modality of treatment. In spite of this
      situation, the profession has made a consistent effort not only to retain this
      type of psychiatric care but also to train psychiatric residents in this
      psychiatric intervention technique and its appropriate indications. In this
      article, the authors highlight a very important aspect of psychotherapy treatment
      the termination phase. They review relevant literature on this subject, discuss
      some of the most common problems faced by psychiatrists, especially psychiatric
      residents, when addressing the termination phase of psychotherapy, and then
      present two cases to illustrate these issues.

PMID- 15990495
TI  - Panic attacks may reveal previously unsuspected chronic disseminated lyme
      disease.
AB  - The author describes the histories of three patients with panic-like episodes
      that turned out to be related to underlying, previously unsuspected tick-borne
      diseases. Each woman experienced symptoms that are not usual in panic disorder
      but are typical of neurological Lyme disease, including exquisite sensitivity to
      light, touch, and sounds, joint pain often in combination with cognitive changes
      including mental fogginess and loss of recent memory, and some degree of bizarre,
      shifting, and often excruciating neurological pain. Because these symptoms are
      atypical of primary panic disorder, they were very helpful in alerting the
      clinician to suspect an underlying physical illness. In each case, the results of
      testing revealed positive hallmarks of disseminated Lyme and other tick-borne
      diseases, including Lyme borreliosis caused by the spirochete, Borrelia
      burgdorferi, babesiosis, and ehrlichiosis. Since beginning treatment with
      intensive doses of appropriate antimicrobial medications for their tick-borne
      infections, all three patients have become free of panic attacks. Treatment of
      their infections by a specialist in Lyme disease allowed one of the women to
      discontinue anti-anxiety medication completely and another to reduce the dose of
      medication to occasional use only. The third patient is no longer anxious but her
      depression is resolving more slowly despite the ongoing use of an antidepressant.
      Two of the patients have also needed ongoing medication for pain and other
      symptoms of late-stage, neurological Lyme disease.

PMID- 15990497
TI  - The neurobiology of the stress cascade and its potential relevance for
      schizophrenia.
AB  - This review explores the neurobiology of stress and its possible role in the
      etiology of schizophrenia. Major life events may play a role in onset and relapse
      in schizophrenia. Other data suggest that early stress exposure increases
      schizophrenia risk, especially in individuals with latent vulnerability. Animal
      research has led to an elucidation of the mechanisms by which stress and cortisol
      are toxic to the hippocampus and impair cognition. Associations among these
      factors have been found in a variety of human conditions, including psychiatric
      illness and normal aging. These mechanisms are plausible in schizophrenia, which
      is characterized by a degree of cortisol dysregulation, hippocampal abnormality,
      and cognitive impairment. Characterization of the role of the stress cascade in
      schizophrenia has implications for novel pharmacologic and other treatment,
      especially for cognitive symptoms, which are debilitating and largely refractory
      to treatment.

PMID- 15990498
TI  - The use of medication for relapse prevention in substance dependence disorders.
AB  - Substance abuse is a significant problem in itself and can greatly complicate the
      symptomatology and treatment of comorbid psychiatric disorders. In the article,
      the authors review literature concerning the use of medication to prevent relapse
      to substance abuse or decrease substance use. Five different general strategies
      are employed for this purpose: 1) use of a drug with pharmacological properties
      similar to the substance of concern (i.e., agonist or substitution therapy); 2)
      use of a receptor antagonist to block or lessen the effects of the substance of
      concern; 3) use of a medication that produces a conditioned aversive reaction to
      the substance of concern; 4) use of a medication to reduce the reinforcing
      properties of the substance of concern; and 5) use of a substance to increase the
      metabolism or clearance of the substance of concern from the body. The authors
      review pharmacological treatments that have been studied for the treatment of
      dependence on the following types of substances: alcohol, sedative-hypnotics,
      opioids, stimulants, nicotine, hallucinogens, cannabis, inhalants, anabolic
      steroids, phencyclidine, and designer drugs. The article ends with a brief
      discussion of the importance of including psychosocial and behavioral
      interventions in any substance abuse treatment program.

PMID- 15990499
TI  - Adult adjustment disorder: a review of its current diagnostic status.
AB  - Adjustment disorder is a diagnosis that is commonly used, particularly in primary
      care and general medical settings. However, there has been relatively little
      research done on this disorder. In this article, the author reviews the
      information that is available on the epidemiology, clinical features, validity,
      measurement, and treatment of adjustment disorder. She first reviews the
      historical development of the diagnosis from transient situational personality
      disorder in DSM-I to its current definition in DSM-IV. The author also considers
      similarities and differences in how adjustment disorder is defined in the DSM and
      ICD systems. The clinical features of the disorder that distinguish it from
      disorders such as major depressive disorder, generalized anxiety disorder,
      posttraumatic stress disorder, and acute stress disorder are described. The
      author highlights a number of the common controversies concerning adjustment
      disorder, especially criticisms that the diagnostic criteria are often poorly
      applied and that the disorder itself involves the medicalizing of problems of
      living. Evidence in support of the validity of the adjustment disorder diagnosis
      is reviewed and the author concludes that the findings support the content and
      predictive validity of the diagnosis. The author then discusses the epidemiology
      of adjustment disorders, their comorbidity with other conditions, including
      personality disorders, substance abuse, and suicidal behavior, and their
      treatment and outcome. The article concludes with a discussion of the special
      problems involved in evaluating for and measuring adjustment disorder.

PMID- 15990500
TI  - Which side effects really matter? Screening for common and distressing side
      effects of antipsychotic medications.
AB  - As a class, the newer antipsychotics are less likely to cause EPS but continue to
      have a range of other, non-EPS, side effects. Most standardized scales for side
      effects of antipsychotics emphasize the physical findings of the motor
      abnormalities of extrapyramidal symptoms (EPS). There is a need for screening
      instruments that include both EPS and non-EPS side effects. This article
      discusses the development of a screening instrument called the Approaches to
      Schizophrenia Communication (ASC). Initially derived from other subjective
      screening measures, the ASC was specifically designed to address the following
      issues pertaining to side effect evaluation of antipsychotics: 1) to cover all
      common and distressing side effects from antipsychotics, not just EPS, and 2) to
      screen for perceived distress, rather than the objective severity of the side
      effect. These two characteristics of the ASC make it possible for it to be given
      directly to the patient (the ASC Self-Report Version) or to be administered by
      mental health clinicians who do not have to be extensively trained in side-effect
      assessments (the ASC Clinician Interview version).

PMID- 15990501
TI  - Multiple medications, multiple considerations.

PMID- 15990503
TI  - Antisocial personality, psychopathy, and forensic psychiatry.

PMID- 15990502
TI  - Keeping the psyche in psychiatry.

PMID- 15990505
TI  - Using the ASC program: a training guide.

PMID- 15990504
TI  - Is this any way to run an election?

PMID- 15990509
TI  - Herbs and nutrients in the treatment of depression, anxiety, insomnia, migraine,
      and obesity.
AB  - Although a multitude of pharmaceutical agents are available for the treatment of
      mood disorders, anxiety and insomnia, many patients have difficulty tolerating
      the side effects, do not respond adequately, or eventually lose their response.
      Many therapeutic herbs and nutrients have far fewer side effects and may provide
      an alternative treatment or can be used to enhance the effect of prescription
      medications. In the article, the authors review the quality of the evidence
      supporting the clinical effects of a number of commonly used types of
      complementary/alternative medicine (CAM) for mood disorders, anxiety, and
      insomnia. They review data on the use of St. John's Wort, S-adenosyl-methionine
      (SAM-e), B vitamins, inositol, omega-3 fatty acids, and choline for mood
      disorders; data on the use of kava and other herbal agents and fish extract for
      anxiety and insomnia; and data on valerian and melatonin for insomnia. The
      authors also discuss the use of CAM to treat migraines, which may be comorbid
      with mood and anxiety disorders, and obesity, which can occur as a side effect of
      psychotropic medications. They consider the data on feverfew and butterbur for
      migraines and on chromium picolinate and the combination of ephedrine and
      caffeine for obesity. The authors also review issues related to comorbid medical
      illness, side effects, drug interactions, dosage, and brand selection.

PMID- 15990510
TI  - Managing treatment-emergent sexual dysfunction associated with serotonergic
      antidepressants: before and after sildenafil.
AB  - Sexual dysfunction is a common and troublesome side effect associated with
      selective serotonin reuptake inhibitors and other antidepressants that reportedly
      occurs in 40%-70% of patients prescribed selective serotonin reuptake inhibitors.
      Management of this iatrogenic condition has relied on "clinical wisdom" derived
      over decades primarily from open-label, non-placebo-controlled, selected case and
      literature review studies. Management approaches fall into four broad categories:
      1) antidote, 2) avoidance, 3) augmentation/switching, and 4) adaptation. Until
      the development of sildenafil (Viagra), none of the existing managements
      demonstrated clear efficacy in systematic, double-blind, placebo-controlled
      trials. Renewed interest in treatment-associated sexual dysfunction emerged
      because of advances in our knowledge of the biological mechanisms of sexual
      functioning, awareness that sexual dysfunction compromises patient adherence to
      treatment, and an improved focus on improving disease management outcomes of
      depression. Recent placebo-controlled studies provide evidence for questioning
      the effectiveness of earlier approaches to the management of sexual dysfunction
      side effects, and suggest improved treatment options with sildenafil. Effective
      management of treatment-emergent sexual dysfunction is a medical necessity in
      order to prevent relapse and recurrence of serious disorders such as major
      depression, which are highly treatment responsive but frequently compromised by
      medication noncompliance due to side effects such as sexual dysfunction.

PMID- 15990511
TI  - Bipolar disorder with comorbid substance abuse: diagnosis, prognosis, and
      treatment.
AB  - Alcohol and drug abuse occur frequently in individuals with bipolar disorder, but
      clinicians may often feel ill-prepared to identify such multi-diagnosis
      syndromes, to contextualize drug abuse alongside affective symptoms, and to
      formulate appropriate treatment strategies. Plausible explanations for high
      comorbidity rates between bipolar illness and substance use disorders are complex
      and likely embrace numerous factors that extend beyond simple, older theories
      about drug use as sheer "self-medication." Evidence from epidemiologic, family
      genetic, pharmacologic, psychosocial, and clinical psychopathology studies
      suggest that a majority of bipolar patients are at risk for developing lifetime
      drug or alcohol-related problems, which may in turn contribute to more varied and
      complex clinical presentations, accelerated relapses, worsening of depressive
      features, poorer lithium response, functional disability, and elevated suicide
      risk. In this article, the author reviews essential concepts about the
      phenomenology and treatment outcome of bipolar illness with substance use
      comorbidities and offers a systematic approach to the diagnosis and management of
      patients with such dual diagnoses.

PMID- 15990512
TI  - The patient with first episode psychosis.
AB  - The authors describe their approach to the patient presenting with a first
      episode of psychosis. This approach differs from the treatment of
      established/chronic patients and is critical in insuring proper assessment and
      initial treatment and may possibly influence the prognosis. Using prototypical
      cases, the authors give an overview of the first encounter, working with the
      family, differential diagnosis, treatment, and prognosis.

PMID- 15990513
TI  - The human genome project and drug discovery in psychiatry: identifying novel
      targets.

PMID- 15990515
TI  - Pregnant patients' refusal of medical care.

PMID- 15990514
TI  - Documenting psychotherapy: getting hep on HIPAA.

PMID- 15990516
TI  - Ziprasidone: a new atypical antipsychotic.

PMID- 15990518
TI  - Olanzapine use in subjects with pervasive developmental disorder displaying
      aggression and/or self-mutilation.

PMID- 15990519
TI  - Medication response in the treatment of patients with anorexia nervosa.
AB  - Anorexia nervosa (AN) is a serious mental disorder, characterized by severely low
      weight and cognitive distortions about body shape and weight. AN is generally
      associated with a constellation of psychological symptoms, including depression,
      anxiety, obsessionality, and ritualistic behaviors. The presence of these
      associated symptoms, together with the great challenge of treating patients with
      AN, has led clinicians to try many psychopharmacologic agents in the treatment of
      these patients, usually to no avail. Investigators have studied a range of
      agents, but have found little, if any, utility in treating underweight patients
      with medication. In this article, the authors review the literature regarding
      medication treatment for patients with AN, propose a theoretical basis for the
      poor response of these patients to the agents that have been tried, and conclude
      with recommendations for treatment strategies and additional research that should
      be pursued to further our understanding of this difficult illness.

PMID- 15990520
TI  - Faith or delusion? At the crossroads of religion and psychosis.
AB  - In clinical practice, no clear guidelines exist to distinguish between "normal"
      religious beliefs and "pathological" religious delusions. Historically,
      psychiatrists such as Freud have suggested that all religious beliefs are
      delusional, while the current DSM-IV definition of delusion exempts religious
      doctrine from pathology altogether. From an individual standpoint, a dimensional
      approach to delusional thinking (emphasizing conviction, preoccupation, and
      extension rather than content) may be useful in examining what is and is not
      pathological. When beliefs are shared by others, the idiosyncratic can become
      normalized. Therefore, recognition of social dynamics and the possibility of
      entire delusional subcultures is necessary in the assessment of group beliefs.
      Religious beliefs and delusions alike can arise from neurologic lesions and
      anomalous experiences, suggesting that at least some religious beliefs can be
      pathological. Religious beliefs exist outside of the scientific domain; therefore
      they can be easily labeled delusional from a rational perspective. However, a
      religious belief's dimensional characteristics, its cultural influences, and its
      impact on functioning may be more important considerations in clinical practice.

PMID- 15990521
TI  - Cognitive-behavioral therapy in schizophrenia.
AB  - The authors review the literature on cognitive-behavioral approaches to the
      treatment of schizophrenia. They begin by providing a historical context to
      explain the recent resurgence of interest in this area. Next, they provide an
      overview of studies of cognitive-behavioral interventions that target poor
      insight, medication nonadherence, and refractory symptoms. Insight and
      nonadherence are emphasized because these are particularly common and problematic
      areas that present major stumbling blocks in the treatment of patients suffering
      from schizophrenia that are not yet sufficiently addressed by the interventions
      clinicians currently have in their treatment arsenal. The authors conclude that
      support exists for the efficacy of interventions derived from cognitive
      behavioral approaches in improving some aspects of insight into illness,
      increasing adherence to medication, ameliorating the severity of symptoms, and
      mitigating other negative consequences of schizophrenia. Finally, the authors
      offer guidelines for future work in this area and emphasize the importance of
      identifying patients who are most likely to benefit from the use of cognitive
      behavioral approaches.

PMID- 15990523
TI  - Antipsychotic drug development in the pre-human-genome era: a full circle.

PMID- 15990522
TI  - Treatment of depression in women: a summary of the expert consensus guidelines.
AB  - Women constitute two-thirds of patients suffering from common depressive
      disorders, making the treatment of depression in women a substantial public
      health concern. However, high-quality, empirical data on depressive disorders
      specific to women are limited, and there are no comprehensive evidence-based
      practice guidelines on the best treatments for these illnesses. To bridge the gap
      between research evidence and key clinical decisions, the authors developed a
      survey of expert opinion concerning treatment of four depressive conditions
      specific to women: premenstrual dysphoric disorder, depression in pregnancy,
      postpartum depression in a mother choosing to breast-feed, and depression related
      to perimenopause/menopause. The survey asked about 858 treatment options in 117
      clinical situations and included a broad range of pharmacological, psychosocial,
      and alternative medicine approaches. The survey was sent to 40 national experts
      on women's mental health issues, 36 (90%) of whom completed it. The options,
      scored using a modified version of the RAND Corporation's 9-point scale for
      rating appropriateness of medical decisions, were assigned one of three
      categorical rankings-first line/preferred choice, second line/alternate choice,
      third line/usually inappropriate-based on the 95% confidence interval of each
      item's mean rating. The expert panel reached consensus (defined as a non-random
      distribution of scores by chi-square "goodness-of-fit" test) on 76% of the
      options, with greater consensus in situations involving severe symptoms.
      Guideline tables indicating preferred treatment strategies were then developed
      for key clinical situations. The authors summarize the expert consensus
      methodology they used and then, for each of the four key areas, review the
      treatment literature and summarize the experts' recommendations and how they
      relate to the research findings. For women with severe symptoms in each area we
      asked about, the first-line recommendation was antidepressant medication combined
      with other modalities (generally psychotherapy). These recommendations parallel
      existing guidelines for severe depression in general populations. For initial
      treatment of milder symptoms in each situation, the panel was less uniform in
      recommending antidepressants, and either gave equal endorsement to other
      treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD;
      hormone replacement in perimenopause) or preferred psychotherapy over medication
      (during conception, pregnancy, or lactation). In all milder cases, however,
      antidepressants were recommended as at least second-line options. Among
      antidepressants, selective serotonin reuptake inhibitors (SSRIs) were recommended
      as first-line treatment in all situations. The specific SSRIs that were preferred
      depended on the particular clinical situation. Tricyclic antidepressants were
      highly rated alternatives to SSRIs in pregnancy and lactation. In evaluating many
      of the treatment options, the experts had to extrapolate beyond controlled data
      in comparing treatment options with each other or in combination. Within the
      limits of expert opinion and with the expectation that future research data will
      take precedence, these guidelines provide some direction for addressing common
      clinical dilemmas in women, and can be used to inform clinicians and educate
      patients regarding the relative merits of a variety of interventions.

PMID- 15990524
TI  - Lessons from my aged patients.

PMID- 15990525
TI  - Psychiatry and the death penalty.

PMID- 15990526
TI  - Proper paranoia.

PMID- 15990528
TI  - Psychodynamic psychotherapy with the elderly.
AB  - The authors first review issues related to the life cycle and the significance of
      time for older adults. They then consider the types of psychopathological
      problems that can occur in older individuals and discuss the indications for and
      the goals and effectiveness of psychodynamic psychotherapy in older patients. The
      next section of the paper addresses technical aspects of psychotherapy with older
      patients, including transference, countertransference, and process issues. The
      article concludes with a consideration of practical problems (e.g., vision or
      hearing deficits) as well as other types of challenges that may need to be dealt
      with in providing psychotherapy to older patients.

PMID- 15990529
TI  - Psychotherapy in the managed care health market.
AB  - The author considers the future of psychotherapy in the managed care health
      market. He focuses on two interrelated questions. How can the efficacy of
      psychotherapy be scientifically demonstrated? Can psychotherapy meet the
      standards of cost-effectiveness set by health plans? He notes that efficacy is
      not enough in the managed care market, in which health plans also focus on the
      rational allocation of resources and economies of scale. The author then turns to
      the question of whether the doctor-patient relationship, which was central to
      American medicine throughout much of the 20th century, can survive in the current
      healthcare climate. He reviews the literature on the efficacy of psychotherapy
      and discusses the criteria for empirically validated treatments proposed by the
      American Psychological Association. He concludes that there is considerable
      support for the premise that the personal qualities of the individual therapist
      that contribute to the formation of the therapeutic alliance are at least as
      important, if not more important, than the specific method of psychotherapy used.
      The author concludes that medicine and psychiatry may be neglecting an important
      and uniquely curative element-the doctor-patient relationship, the human
      encounter that is the foundation of the art and science of medicine.

PMID- 15990530
TI  - Schizophrenia today: what do we know-and how sure are we?
AB  - The growth of our understanding of the biology and treatment of schizophrenia is
      still very much a work in progress. In this article, which introduces a series of
      papers presented at a conference entitled "Schizophrenia: Doing the Right Thing
      Well," held at Northcoast Behavioral Healthcare System (Cleveland, May 2000), the
      authors provide a short overview of what is known about schizophrenia today. He
      briefly reviews findings concerning epidemiology, phenomenology and course,
      neurobiology, and treatment, and highlights some of the most significant findings
      to date as well as areas needing further research. Early evaluation and
      treatment, in advance of the florid presentation of the illness, offer much hope,
      but only if our knowledge of the diagnostic specificity of prodromal and
      neurodevelopmental precursors can be enhanced. Significant advances in medication
      treatment have been made, and the newer antipsychotic medications overall have a
      more benign adverse-effect profile than the older agents, although the specter of
      endocrine/metabolic complications looms as a significant long-term concern. The
      authors conclude that, although many advances in our understanding of the
      etiology and treatment of schizophrenia have been made, much remains to be
      learned.

PMID- 15990531
TI  - The origin and course of schizophrenia: implications for clinical practice.
AB  - The authors first review current evidence concerning abnormalities of brain
      structure and function in schizophrenia and interpret them within a "network"
      pathophysiological model of the disorder. This information is then placed within
      a contemporary neurodevelopmental framework that "roots" the illness in adverse
      events during early pregnancy, which result in a developmentally compromised
      nervous system. They then consider the controversy as to whether the subsequent
      expression of psychosis reflects an active morbid process and, in a more general
      sense, whether the disorder is characterized by subsequent progression and
      clinical deterioration. The authors argue that the developmental and progressive
      models should not be considered in an either-or manner, since this perspective is
      not logical and favors nihilistic approaches to intervention and treatment, but
      rather should be integrated within a lifetime trajectory model. Finally,
      implications for current psychiatric practice are considered.

PMID- 15990532
TI  - Seven keys to relapse prevention in schizophrenia.
AB  - Relapse prevention is a primary goal in the treatment of schizophrenia. Relapse
      can cause significant personal distress, interfere with rehabilitation efforts,
      and result in psychiatric hospitalization. The emergence of psychotic symptoms
      and disruptive behaviors can also lead to arrest and incarceration, particularly
      among patients who are not engaged in treatment. This article focuses on the
      process of relapse in schizophrenia and theoretical foundations of relapse
      prevention. The Program for Relapse Prevention is presented, along with the
      results of a recently completed controlled prospective evaluation. Based upon
      this study and the current literature, the author presents a series of seven
      clinical strategies for optimal relapse prevention.

PMID- 15990533
TI  - Medication treatments for schizophrenia: translating research findings into
      better outcomes.
AB  - The atypical or novel antipsychotics have advanced the treatment of
      schizophrenia, especially given their reduced extrapyramidal side effect
      liability. In this article, the authors examine a number of recently published or
      presented studies of the atypical antipsychotics, many of them post approval
      studies, that shed additional light on this class of medications. Clozapine
      stands alone as a medication for treatment-resistant schizophrenia, but the other
      first-line atypical agents appear to reduce relapse rates during maintenance
      treatment and to have less of a long-term risk for tardive dyskinesia. However,
      additional research is needed to distinguish the atypical antipsychotics from
      each other and to better understand their non-neurological side effects.

PMID- 15990534
TI  - Drug discovery in psychiatry: drilling down on the target of interest.

PMID- 15990535
TI  - Psychotherapy and the work place.

PMID- 15990536
TI  - Competence to consent.

PMID- 15990537
TI  - Psychiatric telemedicine for rural New York.

PMID- 15990538
TI  - Detection and treatment of depressive disorders.

PMID- 15990539
TI  - The bipolar spectrum and the antidepressant view of the world.
AB  - Whereas much progress has been made in the diagnosis and treatment of
      schizophrenia and depression in recent years, bipolar disorder continues to be
      frequently misunderstood, leading to its inconsistent diagnosis and treatment. In
      this article, we seek to identify the causes of this problem and suggest possible
      solutions, based on a critical review of studies concerning the nosology of
      bipolar disorder and the effects of antidepressant agents. Bipolar disorder
      appears to be underdiagnosed as well as frequently misdiagnosed as unipolar major
      depressive disorder. Underdiagnosis can stem from patients' impaired insight into
      mania and failure to involve family members in the diagnostic process and also
      from clinicians' inadequate understanding of manic symptoms. Underdiagnosis may
      also reflect disagreement about the breadth of the bipolar spectrum. We therefore
      propose a heuristic definition of "bipolar spectrum disorder," a diagnosis that
      gives greater weight to family history and antidepressant-induced manic symptoms.
      This diagnosis would include all forms of bipolar illness that are not type I or
      II . The evidence also suggests that antidepressants are probably overused and
      mood stabilizers underused. We consequently recommend aggressive use of mood
      stabilizers and less emphasis on antidepressants. In summary, the state of
      diagnosis and treatment in bipolar disorder is suboptimal. More diagnostic
      attention to the criteria for mania is necessary. In addition, the current
      pattern of antidepressant use in bipolar disorder does not appear to be evidence
      based.

PMID- 15990540
TI  - Dysthymic disorder: integrating research findings into clinical treatment.
AB  - Dysthymic disorder, a form of chronic depression, has been studied over the past
      two decades. A variety of forms of research, from epidemiological research to
      psychopharmacology and psychotherapy outcome studies, has provided data that may
      help clinicians who treat patients with dysthymic disorder. This article reviews
      clinically relevant research studies and applies their findings to the clinical
      setting. Epidemiological research and prospective follow-up studies can define
      the risks of untreated and under-treated chronic depression. Studies on the
      phenomenology of dysthymic disorder can help the clinician assess target
      symptoms. Psychopharmacology and psychotherapy research can help guide treatment
      choices. The emerging literature on combining medication and psychotherapy can
      clarify goals for different phases of treatment. Thus the clinician has a
      significantly greater chance of helping patients with dysthymic disorder now than
      only 20 years ago.

PMID- 15990541
TI  - Delirium: diagnosis, neuropathogenesis, and treatment.
AB  - Delirium affects more than 2 million patients in the United States each year. The
      onset of delirium often occurs after hospitalization and in many cases is due to
      medications or procedures performed during the hospitalization. Unfortunately,
      delirium remains unrecognized in the majority of patients for several reasons.
      This review addresses the diagnostic criteria for delirium, the neurochemistry
      that is believed to be causative, risk factors, measures that may be taken to
      reduce the onset of delirium, and treatment options.

PMID- 15990543
TI  - Drug development in psychiatry and the human genome project: the explosion in
      knowledge and potential targets.

PMID- 15990542
TI  - Skills training as an adjunctive treatment for personality disorders.
AB  - Personality disorders are usually treated with either psychodynamic or supportive
      psychotherapy, with psychotropic medication often used as an adjunctive
      treatment. However, patients with personality disorders pose special treatment
      issues, because their problems are pervasive and long-standing and they have
      entrenched deficits in many areas of functioning. In this article, the authors
      consider the role of skills training in the treatment of personality disorders.
      They describe a two-pronged approach to the treatment of personality disorders
      based on a model of deficit compensation. Because skills training has only been
      investigated in a very limited way in personality disorders, the authors first
      review research on the use of skills training in Axis I disorders as background
      for a discussion of ways in which skills training may be applicable to the
      treatment of Axis II disorders. They describe a number of skills training
      approaches (social skills training, anger management, and conversational skills)
      that can be used for a variety of different Axis I disorders. Skills training
      approaches that are targeted to specific types of disorders (substance use
      disorders, schizophrenia, anxiety disorders, adolescent problems) are also
      described. The authors then review what is known about the use of skills training
      in borderline personality disorder and avoidant personality disorder, and propose
      skills training approaches that may be useful for patients with paranoid
      personality disorder and antisocial personality disorder. Case examples are
      provided to demonstrate how skills training for personality disorders can be
      applied in clinical practice.

PMID- 15990544
TI  - Can we talk?

PMID- 15990545
TI  - False allegations: the role of the forensic psychiatrist.

PMID- 15990546
TI  - An information technology toolkit.

PMID- 15990547
TI  - Private practitioners' perceptions of the changes in their use of treatment
      modalities following participation in managed care panels.
AB  - Private practicing social workers, psychologists, and psychiatrists were surveyed
      to assess their perceptions of how their use of treatment modalities has changed
      since joining managed care panels. Social work respondents report that they
      perceive managed care organizations as certifying them to practice individual
      therapy more since joining managed care panels than they practiced individual
      therapy prior to joining managed care panels. However, they perceive managed care
      organizations as certifying them to practice group and family therapy less often
      since joining managed care panels. Psychologist respondents report that they
      perceive managed care organizations as certifying them less often for all
      treatment modalities except individual therapy. Likewise psychiatrist respondents
      report they perceive managed care organizations as certifying them less often for
      all treatment modalities except medication management. These results have
      potential implications for educators and practitioners interested in pursuing
      careers in solo or group practice.

PMID- 15990549
TI  - Ziprasidone update.

PMID- 15990548
TI  - Terrorism: changing our world.

PMID- 15990550
TI  - Pharmacotherapy of depression in older patients: a summary of the expert
      consensus guidelines.
AB  - Depression in older adults increases disability, medical morbidity, mortality,
      suicide risk, and healthcare utilization. Most studies of antidepressants are
      conducted in younger adults, and clinicians often have to extrapolate from
      findings in populations that do not present the same problems as older patients.
      Older patients often have serious coexisting medical conditions that may
      contribute to or complicate treatment of depression; they tend to take multiple
      medications, some of which may contribute to depression or interact with
      antidepressants; and they metabolize medications slowly and are more sensitive to
      side effects than younger patients. To address clinical questions not
      definitively answered in the research literature, the authors surveyed 50 experts
      on the pharmacotherapy of depressive disorders in older patients. The survey
      contained 64 questions with 857 options: 618 of the options were scored using a
      modified version of the RAND 9-point scale for rating appropriateness of medical
      decisions; for the other 239 options, the experts were asked to write in answers
      or check a box. The experts reached consensus on 89% of the options rated on the
      9-point scale. Categorical rankings (first line/preferred, second line/alternate,
      third line/usually inappropriate) were assigned to each option based on the 95%
      confidence interval around the mean rating. Guideline tables indicating preferred
      treatment strategies were then developed for common and important clinical
      scenarios. The authors summarize the expert consensus methodology and the
      experts' recommendations and discuss how they relate to research findings. The
      experts recommend including both antidepressant medication and psychotherapy in
      treatment plans for nonpsychotic unipolar major depressive disorder of any
      severity, as well as for dysthymic disorder or persistent minor depressive
      disorder. They would also consider using either medication or psychotherapy alone
      for milder depression. For unipolar psychotic major depression, the treatment of
      choice is an antidepressant plus one of the newer atypical antipsychotics, with
      electroconvulsive therapy another first-line option. If the patient has a
      comorbid medical condition that is contributing to the depression, the experts
      recommend treating both the depression and the medical condition from the outset.
      The SSRIs were the top-rated antidepressants for all types of depression, with
      highest ratings for efficacy and tolerability given to citalopram and sertraline.
      Paroxetine was another first-line option, and fluoxetine was rated high second
      line. The preferred psychotherapy techniques for treating depression in older
      patients are cognitive-behavioral therapy, supportive psychotherapy, problem
      solving psychotherapy, and interpersonal psychotherapy. The experts also
      recommended use of psychosocial interventions (e.g., psychoeducation, family
      counseling, visiting nurse services) in addition to pharmacotherapy and
      psychotherapy. Within limits of expert opinion and with the expectation that
      future research data will take precedence, these guidelines provide direction
      concerning common clinical dilemmas in older patients. They cannot address the
      complexities of each individual patient's care and can be most helpful in the
      hands of experienced clinicians.

PMID- 15990551
TI  - Toward an integrated brief psychotherapy.
AB  - The authors argue for an integrated model of brief psychotherapy that includes
      psychoanalytic and cognitive-behavioral approaches, as well as pharmacotherapy
      when necessary. The use of such a model gives the clinician the opportunity to
      tailor the treatment to the individual patient using differential therapeutics.
      In implementing a differential therapeutic approach, dynamic psychotherapy can be
      conceptualized using a health-sickness or psychopathology continuum, which is
      then superimposed upon a psychotherapy continuum ranging from expressive to
      supportive interventions. The use of such a psychotherapy continuum helps
      clinicians tailor the treatment approach to the specific patient. The authors
      first review psychotherapy outcome studies from the last two decades that suggest
      that an integrated approach may be advantageous. They then present findings from
      process studies that highlight the importance of the patient/therapist
      relationship. In the final sections of the article, the authors discuss how to
      use an integrated approach to brief psychotherapy, including the use of
      medication when appropriate. The authors also discuss the use of trial therapy
      during the initial session to help the therapist determine whether a supportive
      or expressive approach will be most appropriate for the individual patient and
      present two case vignettes illustrating the expressive and supportive approaches
      to trial therapy.

PMID- 15990552
TI  - The paraphilic and hypersexual disorders: an overview.
AB  - In this article, the first of a two-part series, the authors present reasons for
      considering the paraphilic and hypersexual disorders together and provide an
      overview of these disorders. The DSM-IV diagnostic criteria for paraphilias are
      reviewed, and proposed criteria for hypersexual disorders are presented. The
      question of whether the paraphilic and hypersexual disorders should be considered
      within the spectrum of obsessive-compulsive disorders is considered. The authors
      then review the epidemiology of these disorders, and discuss some implications of
      recent sexual predator legislation. The authors discuss the etiology of the
      paraphilias and hypersexual disorders, and consider the role of endocrinological
      function, findings from brain imaging and neuropsychological testing, findings
      from primate research, the monoamine hypothesis, the imprinting hypothesis,
      social learning theory, the concept of courtship disorder, the role of obsessive
      compulsive elements, psychodynamic theories, and genetic factors. The
      phenomenology of the paraphilias and hypersexual disorders is discussed,
      including the tendency for multiple paraphilias to co-occur, the lack of a
      specific offender profile, the predominance of males among those with
      paraphilias, the incidence of a history of victimization in individuals with
      paraphilias and compulsive sexual disorders, the onset and course of both types
      of disorders, and the lack of internal motivation for change in individuals with
      paraphilias and hypersexual disorders. The authors then discuss disorders that
      commonly co-occur with paraphilias and compulsive sexual disorders, including
      mood disorders, substance abuse and dependence disorders, attention
      deficit/hyperactivity disorder, anxiety and impulse control disorders, and
      personality disorders. The second article in the series will discuss the clinical
      assessment and the behavioral and psychopharmacological treatment of these
      disorders. A guide for clinicians and patients on where and how to find
      specialized clinicians and treatment resources in the United States will also be
      provided.

PMID- 15990553
TI  - Psychosocial challenges in transplantation.
AB  - The authors review the psychosocial aspects of transplantation. They first review
      psychosocial risk factors that place transplant patients at higher risk for
      noncompliance and negative outcomes. They then discuss what assessments should be
      included in a pretransplantation psychosocial evaluation. Goals of the
      psychosocial evaluation include selection of candidates most likely to benefit
      from transplantation and identification of areas for psychosocial intervention,
      both before and after transplantation. The assessment should address the
      patient's premorbid psychiatric state, past adaptation to stressors, history of
      compliance with treatment, substance abuse history, and level of social support,
      including community and faith-based support systems. Results of psychometric
      assessments may be helpful when considered in conjunction with a clinical
      interview and other sources of information about the patient. It may also be
      helpful to use a screening tool developed specifically to evaluate psychosocial
      factors relevant to transplantation, such as the Psychological Assessment of
      Candidates for Transplantation (PACT) scale and the Transplantation Evaluation
      Rating Scale (TERS). The authors then review issues related to
      psychopharmacologic interventions in transplant patients, including the use of
      antidepressant medication pre- and post-transplant, strategies for avoiding
      delirium associated with immunosuppressive medications immediately post
      transplantation, neuropsychiatric symptoms associated with interferon alpha
      therapy for hepatitis C, and interactions between over-the-counter and herbal
      agents (e.g., St. John's Wort) and immunosuppressive agents. Although limited
      research has been done on nonpharmacologic interventions, such as transplant
      support groups, it appears that certain types of group therapy, in particular,
      cognitive-behavioral groups that target specific risk factors such as depression,
      distress, and compliance, may also offer promising approaches for dealing with
      the problems of transplant patients. The authors then focus on two special
      situations that create particular problems for transplantation teams: liver
      transplantation in patients with alcoholic liver disease (ALD) and obesity in
      transplant patients. The authors conclude that the prognosis for patients with
      ALD who receive liver transplantation is similar to that of non-alcoholics and
      that alcoholism is not a contraindication for liver transplantation. However,
      careful preliminary psychosocial assessment is essential to review candidates for
      factors that are predictive of relapse, while close follow-up post
      transplantation can help improve outcomes. It appears that obesity can increase
      the risk of negative outcomes in transplant patients, although there is currently
      no consensus on the use of obesity as an exclusion criteria. Interventions that
      take into account the special psychological and medical needs of transplant
      patients need to be developed for treating obesity both pre- and post
      transplantation. Improved strategies for identifying high-risk patients and
      finding ways to intervene both pre- and post-transplantation can not only help
      lengthen transplant recipients' life spans, but also improve their adaptation to
      transplantation and lead to improved quality of life.

PMID- 15990554
TI  - Drug development in psychiatry and genomics: from E. coli to man.

PMID- 15990555
TI  - Psychotherapy in a time of terror.

PMID- 15990556
TI  - Psychological aspects of terrorism.

PMID- 15990557
TI  - Trauma and disaster in psychiatrically vulnerable populations.

PMID- 15990559
TI  - Depression in older adults.

PMID- 15990558
TI  - Obesity and medical illnesses in psychiatric patients admitted to a long-term
      psychiatric facility.
AB  - Obesity and associated medical conditions may have an impact on morbidity and
      even mortality in patients with psychiatric disorders. The authors present the
      results of a survey of the prevalence of obesity and selected medical conditions
      among 420 consecutively admitted psychiatric inpatients at a long-stay facility
      and compare these data with those reported in the literature. Female psychiatric
      subjects had considerably higher rates of being either overweight or obese (69%)
      as compared to women in the general U.S. population (51%). Male psychiatric
      subjects did not differ significantly from their counterparts in the general
      population in being overweight or obese (nearly 55%). The majority of psychiatric
      subjects with essential hypertension, diabetes mellitus, dyslipidemias,
      cardiovascular disease, or sleep apnea were either overweight or obese (72%-87%).
      In this cross-sectional study, no associations could be deduced between
      psychotropic drug classes and specific medical conditions. No specific
      psychiatric diagnostic category was associated with a significantly greater
      prevalence of any specific medical condition, except that subjects with
      schizoaffective disorder appeared to have a higher prevalence of type II diabetes
      mellitus (11.6%). Subjects with predominant substance or alcohol abuse or
      dependence disorders had a lower prevalence of obesity and associated medical
      conditions.Obesity-either independently or additively along with a sedentary
      lifestyle, unhealthy dietary habits, and nicotine dependence-may have a serious
      impact on coexisting medical comorbidity in psychiatric patients. Judicious
      monitoring for obesity and rapid pharmacological and nonpharmacological
      intervention, where appropriate, by concerned clinicians may improve several
      coexisting medical conditions in psychiatric patients and thereby improve
      patients' overall quality of life.

PMID- 15990560
TI  - Seroreversion in patients receiving HAART during acute infection 2.

PMID- 15990561
TI  - UK patients risk treatment exhaustion.

PMID- 15990562
TI  - French therapeutic vaccine strategy shows promise.

PMID- 15990563
TI  - Structure of broadly neutralizing 4E10 antibody revealed.

PMID- 15990564
TI  - How effectively does HAART restore immune responses to Mycobacterium
      tuberculosis? Implications for tuberculosis control.
AB  - Use of highly active antiretroviral treatment (HAART) has had a major impact on
      HIV-associated morbidity and mortality in industrialized countries. Access to
      HAART is now expanding in low-income countries where tuberculosis (TB) is the
      most important opportunistic disease. The incidence of TB has been fueled by the
      HIV epidemic and in many countries with high HIV prevalence current TB control
      measures are failing. HAART reduces the incidence of TB in treated cohorts by
      approximately 80% and therefore potentially has an important role in TB control
      in such countries. However, despite the huge beneficial effect of HAART, rates of
      TB among treated patients nevertheless remain persistently higher than among HIV
      negative individuals. This observation raises the important question as to
      whether immune responses to Mycobacterium tuberculosis (MTB) are completely or
      only partially restored during HAART. Current data suggest that full restoration
      of circulating CD4 cell numbers occurs only among a minority of patients and
      that, even among these, phenotypic abnormalities and functional defects in
      lymphocyte subsets often persist. Suboptimal restoration of MTB-specific immune
      responses may greatly reduce the extent to which HAART is able to contribute to
      TB control at the community level because patients receiving HAART live much
      longer and yet would maintain a chronically heightened risk of TB.

PMID- 15990565
TI  - Acquired T-cell sensitivity to TRAIL mediated killing during HIV infection is
      regulated by CXCR4-gp120 interactions.
AB  - BACKGROUND: Sensitivity towards apoptosis induced by ligation of the tumor
      necrosis factor family of death receptors is controlled in part by death receptor
      expression. Whereas cellular activation enhances Fas receptor expression and
      induces Fas sensitivity, such cellular activation neither alters TRAIL receptor
      expression nor induces TRAIL sensitivity. Cells infected by HIV acquire
      sensitivity to TRAIL induced death, although the mechanisms by which this is
      achieved are undefined. OBJECTIVE: To define the mechanism by which cells from
      HIV infected patients acquire sensitivity to TRAIL mediated killing. DESIGN: In
      vitro assessment of TRAIL receptor expression and TRAIL sensitivity. METHODS:
      Treatment of Jurkat T cells, peripheral blood lymphocytes from HIV negative
      donors, or human osteogenic seroma (HOS) cells expressing CD4, CXCR4 or CCR5 with
      T tropic gp120, M tropic gp120, or agonistic antibodies against CD4, CXCR4 or
      CCR5. TRAIL receptors were measured by flow cytometry or reverse transcription
      PCR and TRAIL sensitivity was assessed by incubation with recombinant TRAIL
      followed by Annexin V fluorescein isothiocyanate/Propidium Iodide (PI) staining.
      RESULTS: Treatment of uninfected Jurkat T cells, as well as primary T cells with
      gp120 results in the upregulation of TRAIL death receptor expression and acquired
      sensitivity to TRAIL mediated cell death. The increase in TRAIL death receptor
      expression and acquisition of TRAIL sensitivity requires the chemokine coreceptor
      CXCR4 but not CCR5 or the CD4 receptor. CONCLUSIONS: These results indicate that
      chemokine receptor interactions regulate TRAIL receptor expression and provide an
      explanation for the acquired T cell sensitivity to TRAIL mediated killing death
      during HIV infection.

PMID- 15990566
TI  - Longitudinal analysis of CD8 T-cell responses to HIV and hepatitis C virus in a
      cohort of co-infected haemophiliacs.
AB  - OBJECTIVE: To investigate CD8 T-cell responses to HIV and hepatitis C virus (HCV)
      over time in a group of co-infected children with haemophilia to assess the
      influence of the virus infections on each other and on clinical outcome. DESIGN:
      The HIV and HCV CD8 T-cell response of HLA-A2 co-infected individuals in the
      cohort were analysed at two time points, looking at the frequency and phenotype
      of HIV-specific T cells and assessing overall responses to the two viruses.
      METHODS: Peripheral blood mononuclear cells (PBMC) from 72 HLA-A2 co-infected
      individuals were analysed using an HIV HLA-A2 tetramer and by IFN-gamma ELISpot
      using a panel of HIV and HCV antigens. PBMC from a group of 26 HLA-A2 HIV mono
      infected adults were also analysed as a comparison. RESULTS: We identified two
      distinct patterns of response: some patients had a limited response to either
      virus whilst others made responses to a range of HIV epitopes. HCV responses were
      detected only in those who made multiple responses to HIV epitopes (P<0.0001).
      HCV infection had an influence on the phenotype of HIV-specific CD8 T cells, with
      a reduction in relative perforin and CD57 expression. Lack of functional or
      tetramer-positive HIV-specific T cells was associated with a decline in absolute
      CD4 T-cell counts between the time points (up to 7 years; P = 0.005). CONCLUSION:
      HCV infection has an impact on the phenotype of HIV-specific CD8 T cells. In this
      well-defined cohort, failure to maintain effective CD8 T-cell responses against
      HIV may contribute to disease progression.

PMID- 15990567
TI  - Analysis of the effect of highly active antiretroviral therapy during acute HIV-1
      infection on HIV-specific CD4 T cell functions.
AB  - BACKGROUND: It has been reported that antiretroviral therapy (HAART) during acute
      HIV-1 infection may rescue HIV-1-specific CD4 T cell responses. OBJECTIVE: To
      determine the duration of this preserved response by investigating the long-term
      effects of HAART during acute infection on HIV-specific CD4 T cell function
      related to possible immune control during subsequent therapy interruption.
      METHODS: A longitudinal analysis followed HIV-specific CD4 T cell reactivity in
      17 individuals with well-documented acute HIV-1 infection where five out of 11
      HAART-treated patients stopped therapy and six were untreated. Peripheral blood
      mononuclear cells were stimulated with overlapping peptide pools derived from Gag
      and Nef. Production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by
      CD4 T cells was analysed together with proliferative responses. RESULTS: Absolute
      numbers, but not percentages, of Gag-specific IFN-gamma-, IL-2- or IFN-gamma/IL-2
      producing CD4 T cells were increased in treated compared with untreated
      individuals up to 2 years after seroconversion. HAART during acute HIV-1
      infection was associated with lower viral load but did not result in increased
      proliferation of HIV-specific CD4 T cells. One out of five individuals who
      discontinued therapy showed evidence for immune control. However, patients who
      failed to control viraemia also had measurable proliferative HIV-specific CD4 T
      cell responses and preserved numbers of cytokine-producing CD4 T cells.
      CONCLUSIONS: Early HAART during acute HIV-1 infection resulted in higher numbers
      of HIV-specific IFN-gamma- and IL-2-producing CD4 T cells, but this preservation
      in four out of five patients was not associated with control of viraemia upon
      treatment interruption.

PMID- 15990568
TI  - Identification of a novel HIV-1 complex circulating recombinant form (CRF18_cpx)
      of Central African origin in Cuba.
AB  - BACKGROUND: Analysis of partial pol and env sequences have indicated a high
      diversity of HIV-1 genetic forms in Cuba, including two potential novel
      circulating recombinant forms (CRF): U/H and D/A. OBJECTIVES: To determine
      whether U/H recombinant viruses from Cuba, detected in 7% of samples, represent a
      novel HIV-1 CRF, and to identify non-Cuban viruses related to this recombinant
      form. METHODS: Near full-length genome amplification was carried out by nested
      polymerase chain reaction in four overlapping DNA segments of two
      epidemiologically unlinked viruses in uncultured peripheral blood mononuclear
      cells. The sequences were analysed phylogenetically. Recombinant structures and
      phylogenetic relationships were analysed by bootscanning and by maximum
      likelihood. Searches for related viruses in databases were initially based on
      sequence homology and sharing of signature nucleotides. RESULTS: Both Cuban
      viruses clustered uniformly in bootscans all along the genome with each other and
      with a virus from Cameroon, CM53379, indicating that all three represent the same
      recombinant form. Their genome comprised multiple segments clustering with
      subtypes A1, F, G, H and K, as well as segments failing to cluster with
      recognized subtypes. The newly defined CRF, designated CRF18_cpx, was
      phylogenetically related in partial segments to CRF13_cpx, CRF04_cpx and 36
      additional viruses, most of them from Central Africa. One of the viruses from
      Cameroon, sequenced in the near full-length genome, was a CRF18_cpx/subtype G
      secondary recombinant. CONCLUSIONS: A novel HIV-1 complex circulating recombinant
      form (CRF18_cpx) has been identified that is circulating in Cuba and Central
      Africa.

PMID- 15990569
TI  - HIV-1 MN Env 15-mer peptides better detect HIV-1 specific CD8 T cell responses
      compared with consensus subtypes B and M group 15-mer peptides.
AB  - OBJECTIVE: To compare the ability of three Env (15-mer) peptide sets derived from
      the HIV-1 MN, the subtype B consensus, and the group M consensus to detect HIV-1
      specific interferon (IFN)-gamma responses in HIV-1 subtype B infected subjects.
      METHODS: Peripheral blood mononuclear cells were obtained from 17 HIV-1 subtype B
      seropositive and 5 HIV-1 seronegative subjects. Peptide matrices comprising each
      peptide set were used in IFN-gamma Elispot assays to screen for T cell epitopes.
      Following matrix deconvolution, individual peptides were analyzed by IFN-gamma
      intracellular cytokine-staining to confirm and characterize the responding cells.
      RESULTS: HIV specific IFN-gamma responses were detected in 17 of 17 HIV-1
      seropositive and none of 5 HIV-1 seronegative subjects by Elispot. Within the 17
      HIV-1 seropositives, 16, 14, and 11 subjects responded to MN, B consensus, and
      group M env peptides, respectively. Responses were confirmed by intracellular
      cytokine analysis in 14 subjects and were in the CD3CD8 compartment. Cross
      recognition of 'equivalent' peptides (i.e., peptides mapping to the same sequence
      region from the three peptide sets) was observed in 9 of 17 subjects. Peptide set
      specific responses to individual peptides were also observed; 11, 1, and 1
      subjects demonstrated peptide set specific responses to MN, B consensus, and
      consensus group M, respectively. CONCLUSION: MN derived Env peptides were better
      able to detect HIV-1 specific CD8 T cell responses, many of which were not
      detectable by the equivalent clade or group consensus peptides. No single peptide
      set detected all the IFN-gamma responses within an individual. These results
      demonstrate the importance of reagent selection for monitoring of HIV responses
      in HIV-1 infected individuals and subsequently vaccine recipients.

PMID- 15990570
TI  - Optimal suppression of HIV replication by low-dose hydroxyurea through the
      combination of antiviral and cytostatic ('virostatic') mechanisms.
AB  - BACKGROUND: The hydroxyurea-didanosine combination has been shown to limit immune
      activation (a major pathogenic component of HIV/AIDS) and suppress viral load by
      both antiviral and cytostatic ('virostatic') activities. Virostatics action
      represent a novel approach to attack HIV/AIDS from multiple directions; however,
      the use of these drugs is limited by the lack of understanding of their dose
      dependent mechanism of action and by fear of pancreatic toxicity, even though a
      large review of ACTG studies has shown that hydroxyurea does not increase the
      incidence of pancreatitis. METHODS: In vitro cytostatic and cytotoxic activity,
      inhibition of viral replication and immune activation by pharmacologically
      attainable plasma concentrations of hydroxyurea (10-100 micromol/l) and
      didanosine (1-5 micromol/l) were analyzed by cell proliferation, viability,
      apoptosis and infection assays using peripheral blood mononuclear cells. In vivo,
      600, 900 and 1200 mg daily doses of hydroxyurea in combination with standard
      doses of didanosine and stavudine were studied in 115 randomized chronically
      infected patients. RESULTS: A cytostatic low (10 micromol/l) concentration of
      hydroxyurea inhibited cell proliferation and HIV replication in vitro. A gradual
      switch from cytostatic to cytotoxic effects was observed by increasing
      hydroxyurea concentration to 50-100 micromol/l, predicting that lower doses of
      hydroxyurea would be less toxic and more potent in vivo. The clinical results
      confirmed that 600 mg hydroxyurea was better tolerated, had fewer side effects
      and was more potent in suppressing HIV replication than the higher doses.
      CONCLUSIONS: A bimodal, dose-dependent, cytostatic-cytotoxic switch is an immune
      based mechanism explaining the apparent paradox that lowering the dose of
      hydroxyurea to 600 mg daily induces maximal antiviral suppression in HIV-infected
      patients.

PMID- 15990572
TI  - Rates of antiretroviral resistance among HIV-infected patients with and without a
      history of injection drug use.
AB  - BACKGROUND: There exist concerns regarding the potential for elevated rates of
      antiretroviral resistance among HIV-infected injection drug users (IDUs)
      prescribed highly active antiretroviral therapy (HAART), however, no population
      based study has examined if IDUs have elevated rates of antiretroviral resistance
      in comparison to non-IDUs. OBJECTIVE: To evaluate the time to the development of
      antiretroviral resistance among antiretroviral-naive patients with and without a
      history of injection drug use. METHODS: In British Columbia there is a province
      wide HIV/AIDS treatment program that provides antiretrovirals free of charge. We
      examined all antiretroviral-naive patients initiating HAART between 1 August 1996
      and 30 September 2000 and who were followed to 31 March 2002. The main outcome
      measure was the time to class-specific antiretroviral resistance. Cumulative
      antiretroviral resistance rates among IDUs and non-IDUs were evaluated using
      Kaplan-Meier methods and relative hazards were estimated using Cox regression.
      RESULTS: Overall, 1191 antiretroviral-naive patients initiated HAART during the
      study period. Resistance mutations were observed in 298 (25%) subjects during the
      first 30 months of HAART. In comparison with non-IDUs, the risk of protease
      inhibitor resistance [relative hazard (RH), 0.9; 95% confidence interval (CI),
      0.5-1.6] and non-nucleoside reverse transcriptase inhibitor resistance (RH, 1.5;
      95% CI, 1.0-2.2) were similar among IDUs, and there were no differences in the
      rates of resistance to the sub-classes of nucleoside reverse transcriptase
      inhibitors. CONCLUSIONS: Resistance to all major classes of antiretrovirals were
      similar among IDUs and non-IDUs after 30 months of follow-up. These findings
      should help to allay fears that prescribing HAART to IDUs may result in elevated
      rates of resistance.

PMID- 15990571
TI  - Early virologic failure in HIV-1 infected subjects on
      didanosine/tenofovir/efavirenz: 12-week results from a randomized trial.
AB  - OBJECTIVE: To compare the safety and efficacy of two once-daily antiretroviral
      regimens containing lamivudine (3TC) or tenofovir disoproxil fumarate (TDF), each
      administered with didanosine (ddI) and efavirenz (EFV) as initial therapy to HIV
      1-infected subjects. METHODS: Single centre, randomized (1: 1), open-label study
      in antiretroviral-naive, HIV-infected adults. Subjects commenced either
      3TC/ddI/EFV (3TC group) or TDF/ddI/EFV (TDF group). Safety, Medication Event
      Monitoring System (MEMScap) and plasma EFV concentration monitoring was performed
      over the study period. Comparisons between groups were assessed using chi test
      and linear regression analysis was used to assess the relationship between EFV
      concentrations and virological response. RESULTS: Seventy-seven subjects were
      enrolled prior to recruitment being suspended, 36 to the 3TC group and 41 to the
      TDF group. Intention-to-treat analysis in which last observation carried forward
      (LOCF) found the mean viral log10 load [95% confidence interval (CI)] at weeks 4
      and 12 to be 2.67 (2.47-2.87) and 1.83 (1.74-1.92) for the 3TC group and 2.75
      (2.45-3.05) and 2.28 (1.96-2.6) for the TDF group (P = 0.013). Emergence of
      resistance occurred in five of 41 (12.2%) subjects in the TDF group up to week 12
      compared with none of 36 in the 3TC group, (P < 0.05); these five subjects shared
      similar baseline characteristics (CD4+ cell counts < 200 x 10 cells/l and HIV-1
      RNA > 100,000 copies/ml). Despite MEMScap monitoring showing > 99% adherence in
      all subjects, among the five failures, three had low EFV concentrations.
      CONCLUSION: TDF/ddI/EFV as initial therapy appears to have diminished efficacy in
      subjects with CD4 < 200 x 10 cells/l and viral load > 100,000 copies/ml.
      Treatment failure with resistance was not attributable to baseline resistance,
      efavirenz exposure or poor adherence.

PMID- 15990573
TI  - Reduced interleukin-8 response to Streptococcus pneumoniae by alveolar
      macrophages from adults with HIV/AIDS.
AB  - BACKGROUND: HIV-infected adults are highly susceptible to pneumococcal disease.
      OBJECTIVE: To examine if alveolar macrophages from HIV-infected subjects
      exhibited a failure of cytokine production in response to Streptococcus
      pneumoniae in vitro. DESIGN: Case-control comparison of alveolar macrophages from
      11 HIV-infected and 13 non-infected adults. METHODS: Type 1 opsonized S.
      pneumoniae were used to challenge the alveolar macrophages in vitro. Cell
      supernatant fluid was collected from unstimulated cells, and cells challenged
      with bacteria for 0, 6, 12 and 24 h. Cytokine production (interleukins 1beta, 6
      and 8) was measured in all fluids using an enzyme-linked immunosorbent assay.
      RESULTS: All the cytokines tested increased over time in both HIV-infected and
      uninfected subjects. Interleukin-8 release was significantly lower in HIV
      infected than in non-HIV-infected subjects (P = 0.02). CONCLUSION: Reduced
      interleukin-8 production may result in decreased neutrophil recruitment, and
      hence increased susceptibility to pneumococcal infection in HIV-infected
      subjects.

PMID- 15990574
TI  - Does immune reconstitution syndrome promote active tuberculosis in patients
      receiving highly active antiretroviral therapy?
AB  - OBJECTIVES: To assess whether highly active anti-retroviral therapy (HAART)
      contributes to the presentation of active tuberculosis (TB). DESIGN:
      Retrospective single-centre cohort study. METHODS: A total of 111 HIV-infected
      individuals with active TB were identified at an urban teaching hospital between
      February 1997 and April 2004. Those receiving HAART at the time of TB diagnosis
      were assessed. RESULTS: Nineteen of 111 (17%) were receiving HAART when TB
      developed. Within this group there appeared to be two distinct populations.
      Thirteen of 19, 12 from ethnic or social groups with high background rates of TB,
      developed disease a median of 41 days (range, 7-109) after starting HAART ('early
      TB' group). In six of 19 ('late TB' group), TB occurred a median of 358 days
      after HAART initiation (range, 258-598). The 'early TB' group had lower CD4 cell
      counts when starting HAART in comparison with the 'late TB' group (median; 87
      versus 218 x 10 cells/l; P = 0.04); however no difference was observed in the
      rate of change of CD4 cell count (P = 0.5) or HIV load. Paradoxical reaction rate
      in the 'early TB' group was significantly greater than in the 'late-TB' group (62
      versus 0%, P = 0.02) and greater than in a similar control population who started
      HAART while taking anti-TB therapy (62 versus 30%, P = 0.05). CONCLUSIONS: These
      data suggest anti-HIV treatment may amplify the presentation of active TB. This
      has implications for antiretroviral programmes in countries with high TB rates
      and warrants prospective investigation of a larger cohort.

PMID- 15990575
TI  - HIV prevalence among injecting drug users in England and Wales 1990 to 2003:
      evidence for increased transmission in recent years.
AB  - OBJECTIVE: To describe trends in HIV prevalence among injecting drug users in
      England and Wales between 1990 and 2003. METHODS: Analysis of surveillance data
      from voluntary unlinked anonymous cross-sectional surveys collecting oral fluid
      samples and behavioural information from injecting drug users recruited from both
      drug agency (n = 24,304) and community settings (n = 3628). RESULTS: HIV
      prevalence in England and Wales declined from 5.9% in 1990 to 0.6% in 1996 and
      then remained stable until 1999, after which it increased to 1.4% in 2003. Few
      HIV infections were detected among short-term injectors between 1994 and 1999,
      but in recent years prevalence among this group has increased. Other factors
      associated with higher odds of HIV infection were being recruited in London and
      from community settings, and ever having had a voluntary confidential HIV test.
      Incidence estimated through a force of infection model was 2.8% per annum among
      those injecting for less than a year in London between 1998 and 2003.
      CONCLUSIONS: These data suggest that incidence and prevalence of HIV may have
      increased, whereas other indicators suggest an increase in risk behaviour. It is
      critical that harm reduction measures are reinvigorated, and evolve in response
      to changes in drug use risk behaviours and policy.

PMID- 15990576
TI  - Increased condom use at sexual debut in the general population of Slovenia and
      association with subsequent condom use.
AB  - OBJECTIVES: To describe the extent of condom use at first heterosexual
      intercourse (FHI) in the general population of Slovenia, identify associated
      factors and assess the association with subsequent use. DESIGN: Cross-sectional
      survey comprising the first Slovenian National Survey of Sexual Lifestyles,
      Attitudes and Health. METHODS: Data were collected during 1999-2001 from a
      probability sample of the general population aged 18-49 years. Statistical
      methods for complex survey data were used to carry out weighted analyses.
      RESULTS: Condom use at FHI was reported by 23.6% of men and 21.3% of women. The
      more recently they experienced FHI, the more likely respondents were to report
      condom use (71.7% of men; 63.8% of women with FHI during 1995-1999). Men with FHI
      at age 18 or older and those with higher levels of education were more likely to
      use a condom and those who lost control (because drunk or carried away by
      feelings) less likely. Men seem to have more control over condom use at FHI than
      women. Sexually active men and women who used condom at FHI were 11 and 2.5 times
      more likely to consistently use condoms during the month preceding the interview.
      CONCLUSIONS: Currently, the majority of Slovenian men and women use protection
      against HIV, other sexually transmitted infections, and unplanned conception at
      FHI. The steep increase over time in condom use at FHI suggests that HIV-related
      condom use promotion has had an impact on preventive behaviours and should be
      sustained, especially since condom use at FHI predicts subsequent use.

PMID- 15990577
TI  - Loss of HIV-1-specific T cell proliferation in chronic HIV-1 infection: cause or
      consequence of viral replication?

PMID- 15990578
TI  - Frequent detection of Kaposi's sarcoma herpesvirus in germinal centre macrophages
      from AIDS-related multicentric Castleman's disease.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's
      sarcoma is able to infect several cell types. By investigating hyperplastic lymph
      nodes from AIDS patients with multicentric Castleman's disease, we demonstrate,
      for the first time, by dual colour immunohistochemistry, that KSHV is frequently
      detectable in germinal centre macrophages. These macrophages, which display a
      latency programme and frequently contain apoptotic bodies, may represent a non
      negligible reservoir for the virus in lymphoid organs.

PMID- 15990579
TI  - Lack of resistant mutation development after receiving short-course zidovudine
      plus lamivudine to prevent mother-to-child transmission.
AB  - A short-course regimen of zidovudine plus lamivudine starting from 34 weeks'
      gestation in pregnant women to prevent mother-to-child HIV infection, and
      discontinued after delivery, was evaluated for the development of resistance at 6
      weeks postpartum. No resistant mutation was found in 32 women. One of the three
      infected infants carried the M184V and K219Q mutations.

PMID- 15990580
TI  - Instability of lopinavir/ritonavir capsules at ambient temperatures in sub
      Saharan Africa: relevance to WHO antiretroviral guidelines.
AB  - WHO recommends lopinavir/ritonavir as an antiretroviral option in resource
      limited countries. Lopinavir/ritonavir is recommended to be stored at 2-8 degrees
      C until dispensing, and afterwards, may be kept at < or = 25 degrees C for < or =
      2 months. Anticipating lopinavir/ritonavir use in countries lacking adequate cold
      chains, we assessed its physical and chemical stability at 35 and 45 degrees C.
      Although maintaining chemical stability for 4 weeks at 35 degrees C, at 45
      degrees C the capsules clumped after 7 days, supporting a need for more
      temperature-stable formulations for hotter climates.

PMID- 15990581
TI  - Factors associated with declining HIV testing and failure to return for results
      among pregnant women in Vietnam.
AB  - In a cross-sectional study, 53.2% of 500 antenatal attendees at Hai-Phong
      Hospital accepted HIV testing and 55.3% returned for results. Factors associated
      with declining included opinions about providing testing or that only high-risk
      pregnant women need testing, intention to decline testing, being a housewife,
      perception of poor healthcare support, and worry about husband's disapproval. Low
      educational level was associated with not returning for results. Testing
      programmes need to address husbands' attitudes, low education levels, and
      perceptions of risk.

PMID- 15990582
TI  - First evidence of HIV infection of CD8 lymphocytes expressing CD4 during primary
      HIV-1 infection.

PMID- 15990583
TI  - Human herpes virus 8 in HIV and non-HIV infected patients with pulmonary arterial
      hypertension in France.

PMID- 15990584
TI  - Association between osteopenia/osteoporosis and the serum RANKL in HIV-infected
      patients.

PMID- 15990585
TI  - Response to 'limited benefit of antiretroviral resistance testing in treatment
      experienced patients: a meta-analysis'.

PMID- 15990587
TI  - Paraoxonases and cardiovascular diseases: pharmacological and nutritional
      influences.
AB  - PURPOSE OF REVIEW: To summarize the new articles published in the last year on
      paraoxonases, including their expression in cardiovascular diseases, and
      regulation by pharmacological and nutritional means. RECENT FINDINGS: The
      elucidation of the crystal structure of the paraoxonase 1 (PON1) gene, obtained
      by directed evolution, shows that it consists of a six-bladed beta-propeller with
      a unique active site. PON1 is present in HDL but also in lipoprotein-deficient
      serum, in VLDL and in chylomicrons. PON1 protects lipids in lipoproteins, in
      macrophages and in erythrocytes from oxidation. Cellular PON2 and PON3 were also
      shown to reduce oxidative stress. Beyond its antioxidative properties, PON1
      possesses additional antiatherogenic properties against macrophage foam cell
      formation: attenuation of cholesterol and oxidized lipids influx, inhibition of
      macrophage cholesterol biosynthesis and stimulation of macrophage cholesterol
      efflux. The PON1 gene is regulated by Sp1 and protein kinase C, whereas the PON2
      gene in macrophages is regulated by nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase. PON1 activity and mass are both reduced in cardiovascular
      diseases and the hypocholesterolemic drugs, statins, increase serum PON1 activity
      (by reducing oxidative stress, or by upregulating hepatic PON1 expression).
      Expression of cellular PON2, like PON1, was upregulated by statins. Nutritional
      antioxidants, such as polyphenols, increase PON1 mRNA expression and activity, by
      an aryl hydrocarbon receptor-dependent mechanism. SUMMARY: The elucidation of
      PON1 structure and its active center has enabled a better understanding of its
      mechanism of action, including its physio-pathological substrate(s). Some drugs
      and nutrients including dietary antioxidants and polyphenols considerably
      increase the activities of paraoxonases which, in turn, can reduce oxidative
      stress and atherosclerosis development.

PMID- 15990588
TI  - Cord blood lipoproteins and prenatal influences.
AB  - PURPOSE OF REVIEW: Blood lipoprotein profiles in early life are known to be
      related to and predictive of those in adulthood, but little is known about their
      determinants. Genetic and environmental influences affect cord blood
      lipoproteins, but how this occurs and the relative contribution of these
      influences to the overall profile in healthy newborns remains uncertain. RECENT
      FINDINGS: This review discusses findings from a range of earlier and more recent
      studies, and summarizes the key influences on cord blood lipoproteins. In
      particular, we review the potential contribution of maternal blood total
      cholesterol levels during pregnancy and the increased maternal transmission in
      newborns of mothers with diabetes. SUMMARY: In cord blood, cholesterol levels are
      lower than in adults and the relative proportion present in HDL as opposed to LDL
      is much higher. The currently available evidence suggests that several factors
      influence the composition of cord blood lipoproteins. Although inheritance of
      major monogenic disorders can affect cord lipids in general, the genetic
      contribution appears to be minimal, although effects of the proprotein convertase
      subtilisin/kexine type 9 gene (PCSK9) need fuller exploration in this regard in
      certain ethnic groups. Evidence is summarized that maternal lipoprotein levels,
      particularly those due to diet or induced by pregnancy, influence cord lipid
      levels. Placental insufficiency and other conditions affecting fetal growth and
      the mode of delivery may also influence cord lipoprotein concentrations. How
      maternal glucose tolerance during pregnancy affects cord blood lipoproteins
      remains unclear. In view of increasing evidence that cardiovascular risk may have
      prenatal antecedents, this would seem to be an important area for further
      investigation.

PMID- 15990589
TI  - Adipose tissue fatty acid metabolism and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Fatty acid and triacylglycerol metabolism in adipose tissue
      may be involved in the generation of risk factors for cardiovascular disease and
      type 2 diabetes. Pharmaceutical companies are targeting adipocyte metabolism in
      their search for drugs for treating, or reducing the risk of, these conditions.
      We review new developments in adipose tissue fatty acid metabolism and how that
      might relate to cardiovascular disease. RECENT FINDINGS: Fatty acid release from
      human adipose tissue is oscillatory, with a period of about 12 min. Remarkably,
      oscillatory fatty acid release is also seen in isolated adipocytes. Further
      evidence has emerged that not all adipose depots are equal, and that lower-body
      adipose tissue may exert protective effects against cardiovascular disease. There
      have been a number of developments in the area of fatty acid handling by
      adipocytes. Fatty acid binding proteins are clearly important in regulating fatty
      acid metabolism, with striking protection against atherosclerosis in mice
      deficient in both the binding proteins expressed in adipocytes. The demonstration
      that adipocytes lacking hormone-sensitive lipase still display lipolysis has led
      to the identification of novel lipases that may play crucial roles in adipose
      tissue fatty acid metabolism. Further evidence has accrued of the interaction
      between hormone-sensitive lipase and perilipin, the protein that coats the
      adipocyte lipid droplet. SUMMARY: Recent developments in our understanding of
      adipose tissue fatty acid metabolism open up the possibility of new
      pharmaceutical targets. However, interference with adipose tissue fatty acid
      metabolism is not to be undertaken lightly and needs a clear understanding of the
      normal role of adipocyte lipolysis.

PMID- 15990590
TI  - Muscle lipid metabolism in the metabolic syndrome.
AB  - PURPOSE OF REVIEW: The metabolic syndrome has been emphasized as affecting an
      important subset of individuals at high risk for cardiovascular disease leading
      the National Cholesterol Educational Program Adult Treatment Panel III in
      highlighting awareness of insulin-resistance syndrome. Insulin resistance is
      thought to be an underlying feature of the metabolic syndrome and in the last few
      years efforts have been performed to assess the effects of ectopic fat
      accumulation on whole-body glucose metabolism and on the pathogenesis of insulin
      resistance. RECENT FINDINGS: Abnormality of fatty acid metabolism and ectopic fat
      accumulation within skeletal muscle has been measured using the traditional
      biopsy technique but this field of investigation has been exploited considerably
      more recently thanks to the use of non-invasive H-magnetic resonance
      spectroscopy. Initial data supported the hypothesis that a strong causal
      relationship between increased intra-myocellular lipid (IMCL) content and whole
      body insulin resistance might exist. Indeed, experimental evidence is still
      controversial especially when the modulation of the IMCL content is induced by
      physical exercise and nutritional interventions. SUMMARY: It has been suggested
      recently that the flux of muscular fatty acids as a source of oxidative energy
      may play a pivotal role into the development of the abnormalities of muscle and
      whole-body energy metabolism, potentially as the basis of the pathogenesis of
      obesity, the metabolic syndrome and type 2 diabetes.

PMID- 15990591
TI  - Nonalcoholic fatty liver disease and the metabolic syndrome.
AB  - PURPOSE OF REVIEW: Clinical, epidemiological and biochemical data strongly
      support the concept that nonalcoholic fatty liver disease is the hepatic
      manifestation of the metabolic syndrome. Insulin resistance is the common factor
      connecting obesity, diabetes, hypertension and dyslipidemia with fatty liver and
      the progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and
      hepatocellular carcinoma. RECENT FINDINGS: The association of nonalcoholic fatty
      liver disease with the features of the metabolic syndrome has been confirmed in
      several epidemiological studies. The diagnostic and clinical significance of
      raised liver enzymes has been questioned; advanced hepatic disease may also be
      present in individuals with ultrasonographically detected steatosis and normal
      aminotransferase levels. The role of adipokines (leptin, adiponectin) and
      cytokines (tumor necrosis factor-alpha, interleukin-6, transforming growth factor
      beta) in disease progression is probably pivotal, mediated by oxidative stress.
      The importance of iron accumulation in this process has not been confirmed.
      Treatments aimed at weight loss remain a primary option; among pharmacological
      interventions, insulin sensitizers (glitazones and metformin) have confirmed
      beneficial effects on both biochemical and histological data, but new treatments
      are on the horizon. SUMMARY: Nonalcoholic fatty liver disease prevalence in
      Western countries is high and there is a trend towards a further increase, with
      millions of people at risk of advanced liver disease. The epidemiological
      evidence, the lifestyle origin of the disease and the cost of pharmacotherapy
      make prevention a primary goal, and will contribute to making behavior therapy
      the background treatment. We need specific programs and carefully controlled,
      randomized studies to tackle simultaneously all the components of the metabolic
      syndrome.

PMID- 15990592
TI  - Implementation of cascade testing for the detection of familial
      hypercholesterolaemia.
AB  - PURPOSE OF REVIEW: Cascade testing is an important method for identifying
      individuals at risk of a genetic condition. Recent advances in its application to
      familial hypercholesterolaemia are reviewed to identify potential problems
      impeding its application and the extent to which current data address these
      concerns. RECENT FINDINGS: Different paradigms for cascade testing are being
      applied in national programmes. Current data demonstrates cost-effectiveness, and
      an increased uptake of preventive measures. The relationship between molecular
      and clinical diagnostic methods is discussed. Psychological impacts of a
      diagnosis of familial hypercholesterolaemia are in line with the risks associated
      with the disorder. The efficacy of statins in improving vascular function of
      children with familial hypercholesterolaemia has been demonstrated, but extensive
      safety data are lacking. Ethical arguments support that it is equally acceptable
      for relatives of familial hypercholesterolaemia patients to be contacted by
      healthcare workers as by family members, but the former is likely to be more
      efficient. Concerns about increased life insurance premiums are valid but
      insurance companies are assessing risk realistically, so this should not be a
      barrier to cascade testing. SUMMARY: Current data support the implementation of
      cascade testing for familial hypercholesterolaemia as being feasible and cost
      effective, but national implementation is limited to a small number of countries.
      Funding and the infrastructure to support it may be the major stumbling blocks in
      implementing this technique in many countries. Concerns about the ethics of
      carrying out cascade testing, and the potential psychological damage of DNA
      testing, appear to have been largely addressed for familial
      hypercholesterolaemia.

PMID- 15990593
TI  - Surrogate markers for atherosclerotic disease.
AB  - PURPOSE OF REVIEW: Novel treatment modalities for cardiovascular prevention are
      emerging rapidly. Since it is virtually impossible to evaluate all these new
      compounds in long-term trials using clinical end points, there is an urgent need
      for validated surrogate markers of atherosclerosis to save both time and costs.
      Over the last decade, the use of imaging markers has been widely introduced into
      drug-development strategies. Here we will discuss the most commonly used
      techniques. RECENT FINDINGS: Whereas both testing of endothelial function,
      assessed as flow-mediated dilation, and assessment of carotid intima-media
      thickness have been shown to predict future cardiovascular events, predominantly
      intima-media thickness has been used successfully as a surrogate marker in
      intervention studies. More recently, standardization of intravascular ultrasound
      has also enabled reproducible assessment of coronary atheroma volume.
      Multidetector computed tomography and electron-beam computed tomography have
      proven useful in providing quantitative information on plaque burden and coronary
      calcium content, respectively. Although cardiovascular magnetic resonance (CMR)
      is improving continuously, additional technical improvements will be mandatory
      before this technique can be implemented in multicenter clinical studies.
      SUMMARY: The imaging modalities reviewed here all provide specific information on
      either functionality or morphology of the vasculature. The value of carotid
      intima-media thickness for cardiovascular risk prediction has been studied most
      extensively. Whereas assessment of plaque burden using intravascular ultrasound
      appears to be the most direct way to quantify coronary changes, its predictive
      value for future cardiovascular events remains to be established. Awaiting
      further technical improvements, CMR is expected to provide the most valuable
      information for the evaluation of atherosclerosis in the near future.

PMID- 15990594
TI  - Lipoprotein-associated phospholipase A2 as a target of therapy.
AB  - PURPOSE OF REVIEW: Considerable discussion continues regarding the precise role
      that secreted lipoprotein-associated phospholipase A2 (Lp-PLA2), also called
      platelet-activating factor acetylhydrolase, plays in atherosclerosis. Since
      interest in this enzyme as a putative drug target has been based primarily upon
      its association with low-density lipoprotein (LDL) in human plasma, this review
      will focus on Lp-PLA2 and human coronary heart disease. RECENT FINDINGS: Recent
      reports have linked Lp-PLA2 enrichment not only to the most atherogenic of LDL
      particles but also to the most advanced, rupture-prone, plaques. Electronegative
      LDL has been shown to be highly enriched in Lp-PLA2; and in advanced atheroma, Lp
      PLA2 levels are highly upregulated, colocalizing with macrophages in both the
      necrotic core and fibrous cap. Lp-PLA2 is well placed, whether on an oxidation
      susceptible LDL particle or in the highly oxidative environment of an advanced
      rupture-prone plaque, to hydrolyse oxidized phospholipid and generate significant
      quantities of the two pro-inflammatory mediators, lysophosphatidylcholine and
      oxidized nonesterified fatty acid. Several studies have confirmed that Lp-PLA2 is
      an independent risk factor for cardiovascular events (i.e. myocardial infarction
      and stroke). Although epidemiology studies consistently support a relationship
      between plasma Lp-PLA2 levels and susceptibility to coronary heart disease this
      is not the case for Lp-PLA2 polymorphisms. Two clinical studies have linked the
      Ala-379-->Val polymorphism with a reduced risk of myocardial infarction, but
      functional differences between the AA and VV polymorphs have yet to be
      demonstrated. SUMMARY: Lp-PLA2 is intimately associated with several aspects of
      human atherogenesis. Although various lipid-lowering therapies, such as statins,
      have been shown to reduce plasma levels of Lp-PLA2, none has been studied in
      terms of its ability to lower the large macrophage-mediated upregulation of Lp
      PLA2 within advanced plaques.

PMID- 15990595
TI  - Bibliography. Current world literature.

PMID- 15990596
TI  - Nutrition and metabolism.

PMID- 15990597
TI  - Therapy and clinical trials.

PMID- 15990598
TI  - The pharmacology of antiretroviral nucleoside and nucleotide reverse
      transcriptase inhibitors: implications for once-daily dosing.
AB  - The trend toward once-daily dosing in HIV antiretroviral therapy is based on the
      association between adherence, treatment outcome, and patient preferences.
      Patients prefer simpler treatments, fewer pills, less frequent dosing, and no
      food restrictions. When a regimen meets a patient's preferences, the patient is
      more likely to be adherent, and with good adherence, the regimen is more likely
      to be effective. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
      have been a prime focus for developing once-daily therapies primarily because
      they form the backbone of most current regimens. Within the NRTI class, however,
      drugs differ in their pharmacokinetic properties, such as plasma and
      intracellular half-lives, and thus in their suitability for once-daily dosing.
      For example, newer NRTIs, such as tenofovir and emtricitabine, combine longer
      plasma half-lives with longer intracellular half-lives, prolonging exposure and
      the period of pharmacologic activity. Of equal importance, the clinical impact of
      systemic and intracellular interactions between concomitant drugs defines which
      once-daily drugs may be combined in once-daily regimens. To construct simplified
      and effective therapies for individual patients, clinicians require an
      understanding of the plasma and intracellular pharmacokinetic properties of NRTIs
      and how these properties determine a drug's appropriateness for once-daily dosing
      and placement within a once-daily regimen.

PMID- 15990601
TI  - Theoretically speaking.

PMID- 15990602
TI  - The influence of peripheral iridotomy on the intraocular pressure course in
      patients with pigmentary glaucoma.
AB  - PURPOSE: To evaluate the influence of laser peripheral iridotomy on the long-term
      intraocular pressure course for patients with pigmentary glaucoma. PATIENTS AND
      METHODS: Retrospective analysis of data contributed by members of the American
      Glaucoma Society on patients with bilateral pigmentary glaucoma, who received
      uniocular laser iridotomy. The main outcome measure was the post-laser
      intraocular pressure course of the treated eyes, compared with the fellow,
      untreated eyes. RESULTS: Sixty patients were included in the study, 46 of whom
      were observed for a minimum of 2 years (mean 70.3 +/- 26.0 months; range 24-113
      months). Among the 14 patients who were observed for less than 2 years, the mean
      intraocular pressure in the treated eyes increased 0.36 +/- 2.63 mm Hg, compared
      with the fellow, untreated eyes. Among the 46 patients, observed for 2 years or
      more, the mean intraocular pressure in the treated eyes decreased 4.0 +/- 5.4 mm
      Hg, compared with 1.9 +/- 3.8 mm Hg in the fellow eyes (P = 0.005). However,
      analysis by linear models indicates that a higher mean baseline intraocular
      pressure in the treated eyes accounts for the apparent treatment effect of laser
      peripheral iridotomy. CONCLUSION: The study does not provide support for the
      benefit of laser peripheral iridotomy in the long-term intraocular pressure
      control of patients with pigmentary glaucoma, when the data are subjected to
      rigid statistical analysis. This does not disprove the benefit of laser iridotomy
      in this patient population, but underscores the need for a large, prospective
      study to address the question.

PMID- 15990603
TI  - Clinical predictors of latanoprost treatment effect.
AB  - PURPOSE: To determine the relationship between latanoprost efficacy and clinical
      features of glaucoma. PATIENTS AND METHODS: Study design was retrospective,
      observational case series. The charts of all patients who underwent a one-eyed
      therapeutic trial of latanoprost during the course of their clinical care between
      1997 and 2001 were reviewed. Intraocular pressures of both eyes prior to and one
      month after initiation of latanoprost were recorded. Latanoprost treatment effect
      was calculated by subtracting the change in intraocular pressure (IOP) in the
      fellow eye from the change in the treated eye. The effect of optic disc stage,
      age, race, sex, diagnosis, involved eye, type and number of other glaucoma
      medications, pattern of cupping (concentric, focal, or indeterminate), and pre
      treatment IOP was correlated with the treatment effect. The stage of glaucoma was
      determined by determining the disc damage likelihood scale (DDLS) stage. RESULTS:
      One hundred eighty-six cases were included. Latanoprost treatment effect was 4.5
      +/- 5.7 mm Hg, was moderately correlated with pre-treatment IOP (Pearson's r =
      0.527, P < 0.01), and was weakly inversely correlated with advancing disc stage
      (Pearson's r = -0.194, P < 0.01) and age (Pearson's r = -0.175, P < 0.05). It was
      independent of the other variables studied (P > 0.05). CONCLUSION: Most clinical
      parameters examined in this study were not correlated with latanoprost treatment
      response. A moderate direct correlation was noted with pre-treatment IOP and a
      weak inverse correlation was noted with optic disc stage and age.

PMID- 15990604
TI  - New gonioscopy system using only infrared light.
AB  - PURPOSE: To describe an infrared gonioscopy system designed to observe the
      anterior chamber angle under natural mydriasis in a completely darkened room.
      METHODS: An infrared light filter was used to modify the light source of the slit
      lamp microscope. A television monitor connected to a CCD monochrome camera was
      used to indirectly observe the angle. RESULTS: Use of the infrared system enabled
      observation of the angle under natural mydriasis in a completely darkened room.
      CONCLUSION: Infrared gonioscopy is a useful procedure for the observation of the
      angle under natural mydriasis.

PMID- 15990605
TI  - Timolol/dorzolamide combination therapy as initial treatment for intraocular
      pressure over 30 mm Hg.
AB  - PURPOSE: To determine the intraocular pressure (IOP)-lowering effect of a fixed
      timolol/dorzolamide combination (Cosopt) for patients with IOP over 30 mm Hg.
      STUDY DESIGN: Prospective interventional case series. METHODS: Eighteen patients
      being seen on the Wills Eye Hospital Glaucoma Service with at least one eye with
      an IOP > 30 mm Hg were recruited. None had used any glaucoma medications for at
      least 1 month. IOP was confirmed by diurnal testing. Cosopt was administered at 9
      am and 9 pm. Trough IOP measurements were made at 9 am and peak IOP measurements
      at 11 am at baseline, 1 month, and 2 months. Pretreatment and posttreatment IOPs
      were compared using a paired-samples independent t test. RESULTS: Mean
      pretreatment IOP was 37.5 +/- 1.0 mm Hg. Baseline posttreatment IOP was 18.4 +/-
      0.5 mm Hg (P < 0.01). At 2 months, the mean trough IOP was 21.1 +/- 0.9 mm Hg and
      the peak, 17.6 +/- 0.6 mm Hg (each, P < 0.01, as compared with pretreatment
      baseline IOP). One patient did not respond to Cosopt; two had a clinically
      insufficient response and did not complete the study. Data from these patients
      were included in the analysis. CONCLUSIONS: Over 80% of the eyes responded to
      Cosopt, with an average trough IOP reduction of 40% at 2 months.

PMID- 15990606
TI  - Does postmenopausal hormone replacement therapy affect intraocular pressure?
AB  - PURPOSE: To assess the effects of postmenopausal hormone replacement therapy
      (HRT) on intraocular pressure (IOP). PATIENTS AND METHODS: This was a cross
      sectional controlled study, including 107 women aged 60 to 80 years receiving HRT
      and 107 controls who have never received HRT. All subjects underwent IOP
      assessment and funduscopic photography for cup-to-disc (C/D) ratios, and
      completed questionnaires regarding personal and family history of glaucoma,
      hormone replacement therapy, lifetime estrogen and progesterone exposure, and
      cardiovascular risk factors. Main Outcome Measures included IOP, prevalence of
      increased IOP, and C/D ratios. RESULTS: The groups did not differ in mean IOP
      (15.3 versus 15.3 mm Hg), mean vertical (0.18 versus 0.21) and horizontal (0.17
      versus 0.14) C/D ratios, and in prevalence of increased IOP (15% versus 14%), C/D
      ratio (7% versus 7%), or glaucoma (9% versus 11%). A personal history of ischemic
      heart disease was the only risk factor associated with increased IOP (O.R. =
      4.63, P = 0.003). Lifetime estrogen and progesterone exposure, including
      pregnancies, deliveries, menstruation years, and the use of oral contraceptives
      did not significantly affect the risk for increased IOP. CONCLUSION: Hormone
      replacement therapy and lifetime estrogen and progesterone exposure do not seem
      to affect IOP or the risk for increased IOP. A personal history of ischemic heart
      disease may be associated with a higher risk for this disorder.

PMID- 15990607
TI  - Incidence and management of encapsulated cysts following Ahmed glaucoma valve
      insertion.
AB  - PURPOSE: Encapsulated cysts have been inconsistently reported to occur following
      Ahmed glaucoma valve implant insertion. We are unaware of previous reports
      reviewing their management. The objective of this study was to evaluate the
      occurrence and management of encapsulated cyst formation following Ahmed glaucoma
      valve implant insertion. PATIENTS AND METHODS: Consecutive glaucoma patients who
      underwent Ahmed glaucoma valve implant insertion were studied retrospectively.
      Inclusion criteria included a minimum of 12 months of follow-up. RESULTS: Fifty
      seven patients met inclusion criteria for analysis. Following Ahmed glaucoma
      valve implant insertion, 13 patients (23%) developed an encapsulated cyst. After
      failing medical therapy and needling with 5-fluorouracil, 11 of these patients
      underwent surgical excision to control intraocular pressure. Eight of the eleven
      patients achieved adequate control of intraocular pressure with a mean follow-up
      time post excision of 330 +/- 120 days. CONCLUSION: Encapsulated cysts associated
      with elevated intraocular pressure were commonly seen after Ahmed glaucoma valve
      implant insertion. Failing medical therapy, surgical excision of the cyst is
      effective in lowering intraocular pressure.

PMID- 15990608
TI  - Frequency doubling technology and scanning laser tomography in eyes with
      generalized enlargement of optic disc cupping.
AB  - PURPOSE: To characterize functional and structural changes in eyes with
      generalized enlargement of optic disc cupping (vertical cup/disc ratio > or =
      0.8), normal intraocular pressure, normal standard achromatic automated perimetry
      (SAP) results, and no other ophthalmoscopic findings suggesting glaucoma (large
      C/D eyes) using frequency doubling technology (FDT) and the Heidelberg Retina
      Tomograph (HRT). METHODS: This comparative observational case series included 30
      large C/D eyes (30 subjects), 17 eyes (17 patients) with early-stage normal
      tension glaucoma with generalized enlargement of optic disc cupping (NTG eyes),
      and 25 eyes from 25 normal subjects (normal eyes). Results with Humphrey 30-2,
      FDT N-30 threshold programs, and HRT were compared among these groups. Large C/D
      eyes were subdivided into FDT-normal and -abnormal eyes according to the
      predetermined criteria and HRT parameters were compared among them. RESULTS: No
      significant difference was seen in HRT parameters between the large C/D and NTG
      eyes. In the large C/D eyes, FDT mean deviation was lower than in the normal eyes
      and higher than in the NTG eyes, whereas FDT pattern standard deviation was
      smaller than in the NTG eyes (P = 0.02-0.03). Among HRT parameters, only cup
      shape measure (CSM) showed significant negative correlation with FDT mean
      deviation in the large C/D eyes. Between FDT-normal and -abnormal subgroups, only
      CSM showed significant difference (P < 0.01). CONCLUSION: Frequency doubling
      technology showed abnormalities in large C/D eyes. Only CSM showed significant
      correlation with FDT result and difference between those with normal and abnormal
      FDT results. In management of large C/D eyes, FDT and CSM will be useful to
      detect functional and structural change.

PMID- 15990609
TI  - Comparison of dynamic contour tonometry with goldman applanation tonometry over a
      wide range of central corneal thickness.
AB  - PURPOSE: To compare dynamic contour tonometry with Goldmann applanation tonometry
      in structurally normal corneas over a wide range of central corneal thickness
      (CCT). PATIENTS AND METHODS: Twenty-five patients each with normal CCT (group A),
      thin corneas (group B), and thick corneas (group C) had IOP measured with the
      Goldmann (GAT) and dynamic contour tonometer (DCT). RESULTS: In group A (mean CCT
      = 552 +/- 16 microm) the mean GAT was 15.9 +/- 3.1 mm Hg and mean DCT was 16 +/-
      3.3 mm Hg (P = 0.91). In group B (mean CCT = 491 +/- 19 microm) the mean GAT was
      13.2 +/- 3.5 mm Hg and the mean DCT was 15.9 +/- 3.5 mm Hg (P = 0.009). For group
      C (mean CCT = 615 +/- 22 microm), the mean GAT was 17.4 +/- 3.8 mm Hg and the
      mean DCT was 17.4 +/- 3.5 mm Hg (P = 0.95). The 95% agreement limits for DCT were
      -3.1 mm Hg to 2.9 mm Hg. The mean GAT-DCT difference was -2.6 mm Hg in thin
      corneas and -0.06 mm Hg in thick corneas. Below 520 microm reduction of 10 microm
      in CCT appears to result in a significant underestimation of the GAT IOP by 0.7
      mm Hg (P < .001) and above 580 microm a non-significant overestimation of 0.2 mm
      Hg per 10 microm increase in CCT (P = 0.27). CONCLUSION: Dynamic contour
      tonometer agrees well on average with GAT but the agreement limits are wide. In
      structurally normal thin corneas DCT may give a more accurate assessment of the
      true IOP but it does not appear to have any benefit over GAT in thick corneas.

PMID- 15990610
TI  - Scleral indentation optimizes visualization of anterior chamber angle during
      goniosynechialysis.
AB  - PURPOSE: To propose a new surgical technique for optimized visualization of the
      chamber angle using scleral indentation under an operating microscope in
      goniosynechialysis (GSL). PATIENTS AND METHODS: Six volunteers with normal
      chamber angle and five patients with synechial angle closure glaucoma were
      examined. Scleral indentation 2 mm posterior to the limbus was performed during
      observation of chamber angle. Width of trabecular meshwork in images was recorded
      through a CCD camera mounted on an operating microscope. Trabecular-iris angle
      and trabecular-corneal angle obtained by ultrasound biomicroscopy were used for
      the parameters for the angle configuration. GSL with scleral indentation was
      performed in the patients. RESULTS: According to the visibility of the chamber
      angle, width of trabecular meshwork in images significantly increased from 0.34
      +/- 0.08 mm equivalent (mean +/- SD) to 0.67 +/- 0.14 mm equivalent (P = 0.0001)
      with scleral indentation. According to the angle configurations, trabecular-iris
      angle significantly increased from 39.6 +/- 3.8 degrees to 47.5 +/- 6.6 degrees
      (P = 0.0016), and trabecular-corneal angle significantly decreased from 169.8 +/-
      5.5 degrees to 158.7 +/- 5.4 degrees (P < 0.0001). All patients were successfully
      treated with GSL using scleral indentation. CONCLUSION: Scleral indentation
      provided the surgeon an optimized visualization of the anterior chamber angle.
      Deepening of the chamber angle and steeping in trabecular-corneal curvature
      probably induced the plane of the trabecular meshwork less oblique to the
      surgeon's visual axis. This enhanced visualization promises the accuracy and
      safety of GSL.

PMID- 15990611
TI  - Loss of vision after phacotrabeculectomy.

PMID- 15990612
TI  - The importance of models in glaucoma research.
AB  - Experimental models have enhanced our understanding of the biology of glaucoma.
      Moreover, they have enabled the testing of potential therapies prior to the
      initiation of human trials. Each have advantages and limitations. In vitro cell
      and organ culture offer direct cellular accessibility and microenvironmental
      control, as well as efficient comparison between many experimental conditions or
      potential therapeutic compounds. However, they generally have less relevance to
      clinical glaucoma than in vivo models. Rat models allow moderate sized
      investigations of intact biological systems that have greater relevance to
      glaucoma than in vitro experiments, but less than primate experiments. Mouse
      models are similar to rat models but have the advantage of investigating mutant
      and transgenic strains mimicking specific aspects of glaucoma that are not
      available in other model systems. Primate models of glaucoma generally are the
      most relevant to human glaucoma but must be limited in scope because of
      availability and the high cost of experimentation.

PMID- 15990613
TI  - Retinal ganglion cells and supporting elements in culture.
AB  - Elucidating the pathophysiology of glaucoma has traditionally relied on animal
      models of intraocular hypertension and optic nerve injury, which are closely
      related to the human disease with respect to tissue damage. However, cell culture
      models of retinal neurons (particularly retinal ganglion cells) and supporting
      cells (particularly retinal glia and lamina cribrosa cells), although less
      closely related to glaucoma pathophysiology, have particular advantages in
      understanding intracellular processes associated with glaucomatous optic
      neuropathy. Examples of studies which are more readily achievable with cultured
      cells include: 1) Isolation and separation of purified cells to help define the
      role of classes of cell types; 2) Transfection of genetic material to over
      express or knockdown specific genes; 3) Fluorescent imaging of calcium
      concentrations, reactive oxygen species concentrations, mitochondrial membrane
      potential, cellular pH, and other measures of cellular physiology.

PMID- 15990614
TI  - Trabecular meshwork and uveoscleral outflow models.
AB  - PURPOSE: To describe current laboratory models used to study aqueous outflow.
      Because development of primary open angle glaucoma (POAG) is rare in animals, no
      animal model of POAG is available for laboratory study on the pathogenesis of
      this condition. This review will discuss the alternative models used in the
      laboratory to study aqueous outflow. METHODS: This is a brief review of published
      techniques, with commentary upon advantages and limitations of each. RESULTS:
      Whole eyes and anterior segments are useful in assessing aqueous outflow
      resistance and anatomical changes in the meshwork. They have a limited duration
      of viability. Cell cultures are less expensive, easier to obtain, provide more
      cells than in intact meshwork, and are excellent in studying cellular physiology.
      The artificial environment of cell culture, however, including the plastic dish
      or artificial substrate and also the requirement of serum supplements, may limit
      applicability. Modern understanding of cells, their interaction with the
      extracellular matrix, and sensitivity to the composition of culture media suggest
      that these laboratory models should be updated to more closely mimic the in vivo
      situation. CONCLUSION: Outflow models are a useful beginning in the study of
      cellular physiology, cell-extracellular matrix interactions, and reactions of the
      whole meshwork. All have limitations, however; the development of an animal model
      of human POAG would be an ideal solution to many of the current limitations.

PMID- 15990615
TI  - Primate glaucoma models.
AB  - The monkey model of ocular hypertension (OHT) with its resultant optic neuropathy
      closely reflects the optic neurodegeneration associated with human glaucoma.
      Utilization of the experimental glaucoma model (ExpG) in non-human primates (NHP)
      has led to advances in the understanding of aqueous humor dynamics, glaucomatous
      changes in the visual pathways from photoreceptors to the visual cortex, and
      anterior and posterior ocular segment pharmacological effects.

PMID- 15990616
TI  - Elevated intraocular pressure and optic nerve injury models in the rat.
AB  - Models of experimentally elevated intraocular pressure in rats provide valuable
      opportunities to discover and study mechanisms of pressure-induced optic nerve
      damage. The structure and vasculature of the rat optic nerve head have several
      anatomic similarities and differences from the primate that allow useful
      comparisons and insights into human glaucoma. Specifically, the ultrastructural
      relationship between astrocytes, retinal ganglion cell axons and the connective
      tissues of the optic nerve head appear quite similar to the primate, and have a
      high potential for revealing cellular mechanisms of axonal injury. Three widely
      used models of creating elevated IOP in rats exist. However, they are not all
      equivalent and appear to differ in the relationship they exhibit between the
      level of pressure and extent of optic nerve damage. This indicates that these
      models may differ in the mechanisms by which they produce elevated eye pressure.
      All of these models are amenable to a variety of methods for evaluating damage.
      These include objective and subjective histologic assessment of the optic nerve,
      counting cells in the retinal ganglion cell layer of the retina and the use of
      retinal whole mounts to count retinal ganglion cells that have been back-labeled
      with dye applied to the superior colliculus. In the decade since their
      introduction, these versatile models have provided important insights into
      mechanisms of pressure-induced optic nerve damage using sensitive molecular
      biology techniques. They have also allowed the evaluation of several potential
      strategies for neuroprotection in glaucoma, ranging from currently available
      drugs to gene transfer studies.

PMID- 15990617
TI  - Elevated intraocular pressure and transgenic applications in the mouse.
AB  - Exploitation of the mouse as a model for glaucoma has been advanced by the
      development of methods to measure mouse intraocular pressure (IOP),
      identification of mutant mouse strains in which IOP spontaneously increases, and
      the development of treatments to induce elevated IOP. These developments enable
      investigations that directly test the influence of specific gene product
      alterations on the progression of glaucoma. Moreover, new transgenic mouse models
      have been produced with genetic mutations that parallel human gene mutations that
      have been linked to the onset of glaucoma. These new mouse models and
      technologies have potential for uncovering the biological basis of glaucoma as
      well as for evaluating new treatments.

PMID- 15990618
TI  - Lessons for glaucoma from other neurodegenerative diseases: can one treatment
      suit them all?
AB  - The past decade has seen growing acceptance that glaucoma should be viewed as a
      slowly progressive neurodegenerative disease. According to this view, in glaucoma
      (as in other such diseases), whatever the primary risk factors, at any given time
      some neurons are still healthy but are threatened with destruction owing to the
      toxicity emanating from the degenerating neurons. It follows that any
      intervention that protects surviving neurons and rescues the marginally damaged
      ones should slow down progression of the disease. This novel view of glaucoma
      prompted scientists to compare glaucoma with other neurodegenerative diseases
      with respect to mediators of disease progression and ways in which the spread of
      damage, or 'secondary degeneration', can be attenuated. Studies of partial crush
      injury of the rat optic nerve, a model of secondary degeneration established in
      our laboratory, led us to conceptualize the 'enemy within' as a flood of
      neurotoxic self-compounds issuing from the degenerating nerve. With this model,
      pharmacological and molecular approaches were employed to identify and test
      potentially therapeutic neuroprotective compounds and methodologies, leading us
      ultimately to the serendipitous discovery of protective autoimmunity as the
      body's defense against destructive self-compounds. Mediators of self-perpetuating
      acute and chronic degeneration identified in the injured optic nerve were also
      detected in other sites of central nervous system (CNS) damage. This finding led
      scientists to screen drugs that had proven to be beneficial in other disease
      models for their use in glaucoma therapy. It also opened the way to studies of
      the direct effects of these toxic mediators on retinal ganglion cell survival and
      ways to prevent the degenerative outcome. Although no single model can fully
      simulate human glaucoma or any other neurodegenerative disease, the availability
      of different models of optic nerve damage and the similarity of findings in the
      optic nerve and in other parts of the CNS have led to significant progress toward
      development of a cure for glaucoma.

PMID- 15990619
TI  - Applying the recent clinical trials on primary open angle glaucoma: the
      developing world perspective.
AB  - Recent clinical trials have provided scientific guidelines for the treatment of
      ocular hypertension and primary open angle glaucoma. The developing world need to
      apply these trials in a sensible and cost effective manner. The number needed to
      treat (NNT) attempts to tailor treatment to the individual patient. The NNT for
      the average ocular hypertensive is 20. Those with intraocular pressure > or =26
      mm Hg have an NNT of 6. Restricting treatment to those with lower central corneal
      thickness and or high cup disc ratios can further lower NNT and make treatment
      more cost effective. The NNT for the average patient with early POAG is 5.
      Targeting those at higher risk for progression, (bilateral POAG, higher IOP and
      or pseudo-exfoliation) can further reduce NNT. As far as the modality of
      treatment is concerned, provided quality can be ensured, collaborative initial
      glaucoma treatment study (CIGTS) could be interpreted to justify primary surgery
      in the developing world context. Population attributable risk percentage (PAR), a
      measure that reflects the public health importance of a disease was used to
      extrapolate results to the overall population. Ocular hypertension has an
      "effective" PAR of 8.5%, a value not considered high enough to warrant public
      health intervention. POAG had an "effective" PAR of 16%, perhaps high enough to
      be considered a public health problem and justify inclusion as a target disease
      in the Vision 2020 program. However the logistics and opportunity costs of
      diagnosis and treatment would probably prevent inclusion of POAG in public health
      budgets of most developing countries.

PMID- 15990620
TI  - Inflammatory bowel disease in children and adolescents: recommendations for
      diagnosis--the Porto criteria.
AB  - Ulcerative colitis and Crohn disease may present before the age of 20 years in
      25% to 30% of all patients with inflammatory bowel disease. Reported incidence
      figures vary considerably depending on the collection of data. Multicenter,
      multinational collaboration is needed when studying pediatric inflammatory bowel
      disease. The essential first step is uniformity in the work-up and criteria used
      for diagnosis. The Porto diagnostic criteria presented here provide the tool that
      is needed. These criteria are the result of consensus reached by the ESPGHAN
      inflammatory bowel disease working group. Diagnosis of Crohn disease, ulcerative
      colitis and indeterminate colitis is based on clinical signs and symptoms,
      endoscopy and histology and radiology. Every child suspected of inflammatory
      bowel disease should undergo a complete diagnostic program consisting of
      colonoscopy with ileal intubation, upper gastrointestinal endoscopy and (in all
      cases except in definite ulcerative colitis) radiologic contrast imaging of the
      small bowel. Multiple biopsies from all segments of the gastrointestinal tract
      are needed for a complete histologic evaluation. A diagnosis of indeterminate
      colitis cannot be made unless a full diagnostic program has been performed.

PMID- 15990621
TI  - The need for nutrition support teams in pediatric units: a commentary by the
      ESPGHAN committee on nutrition.
AB  - The reported prevalence of malnutrition in pediatric hospitals ranges from 15% to
      30% of patients, with an impact on growth, morbidity and mortality. Major
      deficits in nutrition care have been highlighted in European hospitals, and the
      implementation of nutrition support teams (NSTs) has been suggested as a means to
      improve malnutrition diagnosis and nutrition care for hospitalized patients. This
      comment by the ESPGHAN Committee on Nutrition reviews disease related-mechanisms
      causing malnutrition and consequences of malnutrition and suggests a framework
      for implementation of NSTs in pediatric units. The recommendations by the
      Committee on Nutrition include: 1) Implementation of NSTs in hospitals is
      recommended to improve nutritional management of sick children; 2) The main tasks
      of the NST should include screening for nutritional risk, identification of
      patients who require nutritional support, provision of adequate nutritional
      management, education and training of hospital staff and audit of practice; 3)
      The NST should be multidisciplinary, with expertise in all aspects of clinical
      nutrition care; 4) The funds needed to support NSTs should be raised from the
      health care system; and 5) Further research is needed to evaluate the effects of
      NSTs in prevention and management of pediatric nutritional disorders, including
      cost effectiveness in different settings.

PMID- 15990622
TI  - Should we add oil to complementary foods for breastfed children in developing
      countries?

PMID- 15990623
TI  - Infantile proctocolitis: are we empirically too casual?

PMID- 15990624
TI  - Prevalence and outcome of allergic colitis in healthy infants with rectal
      bleeding: a prospective cohort study.
AB  - OBJECTIVES: Allergic colitis is often diagnosed clinically in healthy infants
      with rectal bleeding and often treated with costly hypoallergenic formula. The
      true prevalence of allergic colitis is unknown. We tested the hypothesis that
      allergic colitis is overdiagnosed in healthy infants with rectal bleeding. The
      authors also determined whether rectal bleeding in infants without allergic
      colitis would resolve without diet change. METHODS: For the purposes of this
      study, allergic colitis was defined histologically as colonic mucosa with >or= 6
      eosinophils per high power field and/or eosinophils in colonic crypts or
      muscularis mucosae. We surveyed all 56 Ohio NASPGHAN members to determine
      standard practice regarding the evaluation of rectal bleeding in infants. In
      addition, infants <or= 6 months old with rectal bleeding were recruited from the
      referral area of Cincinnati Children's Hospital Medical Center. All infants
      underwent flexible sigmoidoscopy with biopsies at 5, 10 and 15 cm. Formula or
      maternal diet was changed only for infants with histologic findings of allergic
      colitis as defined. Study subjects were followed for 9 weeks. RESULTS: In the
      survey of NASPGHAN members, 84% indicated they would empirically change the diet
      of an infant with rectal bleeding to treat presumed allergic colitis. In our
      study population, however, only 14 of 22 (64%; 95% confidence interval, 41-83)
      infants with rectal bleeding had allergic colitis. Five (23%) had normal biopsies
      and three (14%) had nonspecific colitis. Rectal bleeding in all infants with
      normal biopsies or nonspecific colitis resolved without diet change except for 1
      infant subsequently diagnosed with infantile inflammatory bowel disease.
      CONCLUSION: A significant proportion of infants with rectal bleeding may not have
      allergic colitis and may undergo unnecessary, expensive formula or maternal diet
      changes that may discourage breast-feeding.

PMID- 15990625
TI  - Frequency of ASCA seropositivity in children with cystic fibrosis.
AB  - OBJECTIVE: To determine the frequency of anti-Saccharomyces cerevisiae antibodies
      (ASCA) seropositivity in pediatric patients with cystic fibrosis (CF) and
      correlate ASCA with clinical features. METHODS: Prospective study of children
      with CF aged 2 to 21 years enrolled from The Children's Hospital Cystic Fibrosis
      Center. Exclusion criteria included Crohn disease, immunodeficiency or
      immunoglobulin A deficiency. The frequency of ASCA (ASCA immunoglobulin A and
      immunoglobulin G) was measured by an enzyme-linked immunosorbent assay kit
      provided by Inova, Inc. (San Diego, CA). The CF Foundation database was queried
      for clinical data on ASCA seropositive patients. RESULTS: Seventeen (20.7%) of 82
      patients were seropositive for ASCA. Of these, eight had immunoglobulin A
      antibodies, six had immunoglobulin G antibodies and three had both. ASCA
      seropositivity in CF patients was significantly greater than the general
      population (20.7% versus 4%, P < 0.0001), using an exact binomial test on a
      single proportion. The 95% confidence limits around our observed proportion were
      12.6% to 31.1%. Of 17 ASCA positive patients, 1 (5.8%) had a history of meconium
      ileus, 14 (82.4%) had DeltaF508 gene mutation, 9 (52.9%) had positive sputum
      cultures for fungal organisms, and 17 (100%) had an ideal body weight % >or=85%.
      CONCLUSION: Patients with CF have a higher frequency of ASCA seropositivity than
      the general population. When evaluating CF patients for Crohn disease, ASCA
      should be used with caution. The reasons for higher ASCA seropositivity in CF
      patients are unknown, but may include exposure to fungal organisms via intestinal
      or pulmonary sources.

PMID- 15990626
TI  - Influence of CARD15 mutations on disease activity and response to therapy in 65
      pediatric Crohn patients from Saxony, Germany.
AB  - OBJECTIVES: Certain genetic variants in the CARD15 gene are accompanied by an
      enhanced risk to develop Crohn disease with the main activity in the terminal
      ileum and ensuing stricturing early in life. The objective of this study was to
      evaluate the relation between CARD15 mutations and overall disease activity and
      response to therapy in pediatric patients. METHODS: 65 genomic DNA samples from
      such patients were tested for the presence of three main Crohn associated
      mutations in CARD15 by direct genomic sequencing. The number of mutations (none,
      one or two alleles affected) was correlated with body mass index and height,
      Pediatric Crohn Disease Activity Index, therapy and therapeutical success in
      terms of body mass index and Pediatric Crohn Disease Activity Index improvement.
      RESULTS: The authors found a nonsignificant trend of a lower body mass index and
      higher Pediatric Crohn Disease Activity Index in patients with CARD15 mutations.
      Physicians uninformed about their CARD15 status prescribed significantly more
      budesonide and prednisolone intermittently and more alimentary supplementation to
      these patients. The average improvement in terms of body mass index and Pediatric
      Crohn Disease Activity Index after 2 years of therapy was roughly similar in all
      patient groups. CONCLUSIONS: Pediatric Crohn patients with CARD15 mutations have
      a higher disease activity and need a more intensive therapy. With some
      exceptions, their medium-term response to therapy is nevertheless satisfying.

PMID- 15990627
TI  - Helicobacter pylori infection and abdominal symptoms among Swedish school
      children.
AB  - BACKGROUND: The role of Helicobacter pylori infection in the etiology of
      abdominal symptoms remains unclear. Our aim was to investigate the association
      between type-specific H. pylori infection and gastrointestinal symptoms among
      school children in Stockholm, Sweden. METHODS: In a community-based cross
      sectional study, 695 children aged 10-12 years participated with a blood sample
      and a questionnaire on sociodemographic characteristics and gastrointestinal
      symptoms, including minor abdominal pain not necessitating medical consultation,
      during the preceding six months. Infection was investigated by an enzyme-linked
      immuno-sorbent assay and confirmed by immunoblot and urea breath test. RESULTS:
      Abdominal pain was reported by 440 (63%) children and recurrent abdominal pain
      (RAP) by 88 (13%). Of 112 (16%) infected children, 73% had antibodies to CagA and
      59% to VacA. There was no positive association between H. pylori status and the
      occurrence of abdominal pain; in fact, the association with any abdominal pain
      report was inverse (odds ratio [OR] 0,5; 95% Confidence Interval [CI] 0.3-0.8),
      while RAP was unrelated to the infection (OR 1.0; 95% CI 0.5-2.1) when adjusted
      for gender, age and family background variables. The prevalence of RAP tended to
      be lower among children harboring CagA+/VacA+ infections than among the
      uninfected (adjusted OR 0.3; 95%CI 0.1-1.1). Furthermore, CagA+/VacA+ infected
      children reported less acid regurgitation (adjusted OR 0.2; 95% CI 0.1-0.5).
      CONCLUSIONS: Taking background factors into account, the presence of H. pylori is
      not accompanied by an increased occurrence of abdominal symptoms in Swedish 10-12
      year-olds. However, unexpected differential associations with strain specific
      infections may indicate a so far overlooked complex relationship that needs to be
      further confirmed.

PMID- 15990628
TI  - Antibiotic-induced mesenteric adenopathy in an intussusception mouse model: a
      randomized, controlled trial.
AB  - BACKGROUND: Idiopathic intussusception is a leading cause of intestinal
      obstruction in young children. Although the etiology remains obscure, lymphoid
      hyperplasia is found in a majority of cases. Antibiotics, the most frequently
      prescribed medication class in the pediatric population, have been recently
      associated with intussusception. The authors sought to determine whether enteral
      antibiotic exposure influences the development of mesenteric adenopathy, bowel
      dilation or intussusception in an animal model. MATERIALS AND METHODS: The
      authors conducted a randomized, controlled animal trial using a previously
      described intussusception model. Mice were gavaged with normal saline,
      amoxicillin-clavulanate or azithromycin twice daily for 5 days to assess the
      influence of enteral antibiotic exposure on intussusception, mesenteric
      adenopathy and bowel dilation. One pediatric surgeon performed all laparotomies
      and was blinded to group designation. Chi2 and Fisher exact tests were used to
      evaluate differences between antibiotic exposed and control groups. RESULTS:
      Mesenteric adenopathy was identified in 4.1% of the normal saline controls
      compared with 54.1% (P < 0.01) and 38.9% (P < 0.01) of the amoxicillin
      clavulanate and azithromycin exposed animals, respectively. A total of four
      intussusceptions were observed in the antibiotic-exposed groups combined whereas
      no intussusception cases were identified in the control group (P = 0.30).
      CONCLUSIONS: This is the first study to describe a significant association
      between antibiotic use and mesenteric adenopathy in any animal species.

PMID- 15990629
TI  - Celiac disease: from inflammation to atrophy: a long-term follow-up study.
AB  - OBJECTIVES: Celiac disease develops gradually from lymphocytosis, crypt
      hyperplasia and minor villous atrophy to overt villous atrophy. It IS NOT known
      how such minor mucosal changes predict eventual celiac disease. The aim of this
      study was to evaluate the role of intraepithelial lymphocytosis and marginally
      decreased villous height/crypt depth ratio in the development of overt villous
      atrophy in a long-term follow-up. METHODS: The authors evaluated 980 small bowel
      biopsies of children who had previously been studied and found to be
      histologically negative for celiac disease between 1976 and 1992. Villous
      height/crypt depth ratio and the number of intraepithelial lymphocytes were
      measured in these initial biopsies. Cases with slight biopsy changes were
      identified for further study and sex and age matched subjects with normal
      biopsies from same group were selected as controls. They all were asked to submit
      serum samples for gliadin, endomysial and tissue transglutaminase antibodies 8 to
      28 years after the initial biopsy. Those with positive screening tests were asked
      to undergo endoscopy and small intestinal biopsy. RESULTS: 236 cases with slight
      changes were identified, and 236 with normal mucosa served as controls; 76 cases
      and 68 controls participated in the follow-up study. Ten individuals had positive
      screening test results. Two new celiac disease patients, one in each group, were
      found. Four patients in the case group had been diagnosed with celiac disease by
      routine procedures during the follow-up. Thus, five cases and one control had
      developed celiac disease. CONCLUSIONS: Small bowel mucosal lymphocytosis or
      slight reduction in villous height/crypt depth ratio are common findings in
      patients with suspicion of celiac disease. These findings alone are poor
      predictors of celiac disease.

PMID- 15990630
TI  - Incidence, clinical presentation and location at diagnosis of pediatric
      inflammatory bowel disease: a prospective population-based study in northern
      France (1988-1999).
AB  - OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory
      bowel disease in children and adolescents in northern France between 1988 and
      1999. METHODS: A 12-year prospective population-based study was conducted by
      gastroenterologists and pediatric gastroenterologists of northern France
      (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of
      childhood inflammatory bowel disease were recorded (7.2% of all inflammatory
      bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative
      colitis and 20 indeterminate colitis. The mean standardized incidence was
      3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8
      for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease
      location at diagnosis was: small bowel and colon (71%), colon only (10%) and
      small bowel only (19%). Location of initial ulcerative colitis was: proctitis
      (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis
      incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in
      1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of
      Crohn disease in the children of northern France showed an increasing trend (20%;
      not significant) during the 12-year period while the incidence of ulcerative
      colitis remained stable. In the entire population(children and adults)the
      incidence of Crohn disease increased significantly (+23%; P < 0.001), while the
      incidence of ulcerative colitis decreased (-17%; P < 0.0001).

PMID- 15990631
TI  - Chronic childhood constipation is associated with impaired quality of life: a
      case-controlled study.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of chronic
      constipation on children's quality of life. METHODS: From October 2002 to
      November 2003, 224 children (140 male, 84 female, aged 10.6 +/- 2.9 years) and
      224 parents were evaluated by a health related quality of life tool during
      initial outpatient consultation. Children with constipation (n = 80) were
      compared with controls with inflammatory bowel disease (n = 42), controls with
      gastroesophageal reflux disease (n = 56), and with healthy children (n = 46).
      RESULTS: Children with constipation had lower quality of life scores than did
      those with inflammatory bowel disease (70 versus 84; P < 0.05), gastroesophageal
      reflux disease (70 versus 80; P < 0.05), and healthy children (70 versus 88; P <
      0.05). Children with constipation reported lower physical scores than did
      inflammatory bowel disease patients (75 versus 85; P < 0.02), gastroesophageal
      reflux disease patients (75 versus 85; P < 0.05), or healthy children (75 versus
      87; P < 0.05). Parents of children with constipation reported lower scores than
      did their children (61 versus 70; P < 0.05). Children with constipation had
      longer duration of symptoms than did the controls with inflammatory bowel disease
      and gastroesophageal reflux disease (43.8 months versus 14.2 months; P < 0.001).
      Prolonged duration of symptoms for children with constipation correlated with
      lower parent-reported scores (P < 0.002). CONCLUSIONS: At initial evaluation,
      children with constipation have a lower quality of life than do children with
      inflammatory bowel disease or gastroesophageal reflux disease. Self-reported
      lower scores may be a reflection of impaired physical ability. Parental
      perceptions of low quality of life are probably impacted by the duration of their
      child's symptoms and by family members with similar complaints. Practitioners
      should be aware of the high level of parental concern and the relatively low self
      reported and parent-reported quality of life in children with chronic
      constipation as they plan therapy.

PMID- 15990632
TI  - Short-term effect of oil supplementation of complementary food on total ad
      libitum consumption in 6- to 10-month-old breastfed Indian infants.
AB  - OBJECTIVES: To evaluate the short term effect of oil supplementation of
      complementary food on total ad libitum consumption in breastfed infants. METHODS:
      Twenty infants between 6 to 10 months of age were studied in a tertiary hospital
      in New Delhi for 48 hours. They were given three semi-solid complementary feeds
      per day and ad libitum breastfeeding. No other food or fluid was allowed during
      the study period. A traditional gruel made of rice and pulses with high energy
      density (oil added; caloric density = 35 kcal/100 g) or low energy density
      (without oil; caloric density = 20 kcal/100 g) was offered in a randomized manner
      on consecutive days to all infants. Total caloric intake from breast milk and
      semi-solids was computed for each day. RESULTS: Infants consumed an equivalent
      amount of semi-solid (mean difference, 10.75 g/day; 95% confidence interval,
      10.56 to 32.06; P = 0.304) and a lower amount of breast milk (mean difference,
      121.1 g/day; 95% confidence interval, 35.13 to 207.16; P = 0.008) when high
      energy density feeds were offered. Although the caloric intake from semi-solids
      increased significantly (18.9 kcal/day; 95% confidence interval, 12.9 to 24.8; P
      < 0.001) with the high density diet, the total caloric intake (breast milk and
      study feeds) decreased (mean difference = 59.6 kcal/day; 95% confidence interval,
      5.95 to 113.34; P = 0.031). An inverse relationship was found between caloric
      density of semi-solids and breast milk intake (r = 0.34, r = 0.12, P = 0.032).
      CONCLUSION: In the short term, oil supplementation of complementary food in
      breastfed infants does not translate into enhanced total caloric intake,
      primarily as a result of breast milk displacement.

PMID- 15990633
TI  - A randomized controlled trial of enteral glutamine supplementation in very low
      birth weight infants: plasma amino acid concentrations.
AB  - OBJECTIVE: Glutamine depletion has negative effects on the functional integrity
      of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants
      are susceptible to glutamine depletion, as enteral nutrition is limited in the
      first weeks of life. Enteral glutamine supplementation may have a positive effect
      on feeding tolerance, infectious morbidity and short-term outcome. The aim of the
      study was to determine the effect of enteral glutamine supplementation on plasma
      amino acid concentrations, reflecting one aspect of safety of enteral glutamine
      supplementation in VLBW infants. METHODS: In a double-blind placebo-controlled
      randomized controlled trial, VLBW infants (gestational age <32 weeks or birth
      weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or
      isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of
      life. Supplementation was added to breast milk or to preterm formula. Plasma
      amino acid concentrations were measured at four time points: before the start of
      the study and at days 7, 14 and 30 of life. RESULTS: Baseline patient and
      nutritional characteristics were not different in glutamine (n = 52) and control
      (n = 50) groups. Plasma concentrations of most essential and non-essential amino
      acids increased throughout the study period. There was no effect of enteral
      glutamine supplementation. In particular, the increase of plasma glutamine and
      glutamate concentrations was not different between the treatment groups (P = 0.49
      and P = 0.34 respectively, day 30). CONCLUSIONS: Enteral glutamine
      supplementation in VLBW infants does not alter plasma concentrations of
      glutamine, glutamate or other amino acids. Enteral supplementation in a dose of
      0.3 g/kg per day seems safe in VLBW infants.

PMID- 15990634
TI  - A graded model of dietary zinc deficiency: effects on growth, insulin-like growth
      factor-I, and the glucose/insulin axis in weanling rats.
AB  - OBJECTIVE: Severe zinc (Zn) deficiency inhibits growth, insulin storage and
      release. Mild or moderate Zn deficiency may also have profound physiological
      effects that are not outwardly evident. We examined the effects of graded levels
      of low Zn intake on growth, insulin-like growth factor-I (IGF-I) and glucose
      homeostasis in weanling rats. METHODS: Weanling rats were fed ad libitum for 3
      weeks with diets containing different Zn levels: very low Zn, low Zn or mildly
      low Zn; there was also a control group and an additional group was pair-fed to
      very low Zn rats. Growth and food intake were recorded. Serum Zn, IGF-I, IGF
      binding protein-3 (IGFBP-3), serum insulin and glucose, tissue Zn and jejunal
      sucrase activity were measured. Relative liver IGF-I and IGFBP-3 mRNA levels were
      quantified. RESULTS: Serum and tissue Zn were significantly lower in rats fed
      very low Zn (compared with pair-fed animals and controls) and low Zn (compared
      with controls). Growth was significantly lower in rats fed very low Zn and pair
      fed animals (compared with controls) and in those fed very low Zn (compared with
      pair-fed animals). Liver IGF-I and IGFBP-3 mRNA levels were higher in low Zn
      animals compared with controls. Serum IGF-1 and IGFBP-3 levels were not affected
      by diet. Serum glucose was significantly higher in rats fed very low Zn than in
      pair-fed animals (191 +/- 28 vs 99 +/- 5 mg/dL, respectively). Sucrase activity
      was lower in rats fed very low Zn than in pair-fed animals or controls and a
      linear relationship was observed between serum glucose and insulin (r = 0.65, P <
      0.01) in pair-fed animals and controls but not in Zn-deficient groups.
      CONCLUSION: Severe Zn deficiency was associated with hyperglycemia and relative
      hypoinsulinemia. Mild degrees of Zn deficiency also altered glucose metabolism,
      suggesting that Zn intake may be a sensitive regulator of glucose homeostasis.

PMID- 15990635
TI  - Whole body protein turnover and urea production of preterm small for gestational
      age infants fed fortified human milk or preterm formula.
AB  - OBJECTIVES: To investigate protein metabolism and urea production in preterm
      small for gestational age neonates fed a preterm formula or fortified human milk.
      METHODS: Ten preterm small for gestational age neonates were fed either their own
      mother's milk fortified with a powdered protein mineral supplement or a special
      preterm formula. Protein metabolism was determined using constant steady-state
      infusion of L-[ring-2H5]phenylalanine and L-[1-13C]valine. Urea production was
      determined from steady-state [13C]urea kinetics. RESULTS: Mean protein intake was
      24% higher in the preterm formula group than in the fortified human milk group.
      No differences in protein turnover, synthesis and breakdown were observed between
      the two groups, but protein accretion was 71% to 79% higher in the preterm
      formula group than the fortified human milk group. Urea production rates were not
      different in the two groups. There was a strong negative correlation between urea
      production and protein accretion calculated from phenylalanine kinetics but not
      when calculated from valine kinetics. CONCLUSIONS: Preterm formula and fortified
      human milk appear equally well tolerated by preterm small for gestational age
      neonates, but protein accretion was higher in the preterm formula group. In
      preterm small for gestational age infants, both phenylalanine and valine kinetic
      methods can be used to accurately determine protein metabolism.

PMID- 15990636
TI  - Neonatal and infant feeding: effect on bone density at 4 years.
AB  - OBJECTIVE: The aim of this study was to determine whether the type of feeding
      during the first 4 months of life affects bone mineral density at 4 years of age.
      METHODS: Healthy 4-year-old children were recruited from the offices of primary
      health care providers. After confirming the type of infant feeding by history,
      dual energy x-ray absorptiometry analysis was obtained at the University of
      Nebraska Medical Center and evaluated by a radiologist blinded as to feeding
      type. RESULTS: One hundred and seventy-eight children completed the study (58%
      male, 85% Caucasian; mean age, 4.5 years). All children had exclusively consumed
      human milk (n = 57), an infant formula containing no palm olein oil (n = 56) or
      an infant formula containing palm olein oil (n = 65) during the first 4 months of
      life. At 4 years of age, no significant differences were noted in bone mineral
      content or bone mineral density (P = 0.51 and 0.89, respectively) among the three
      feeding groups as measured by dual energy x-ray absorptiometry. Total body bone
      mineral content and bone mineral density varied by gender, with males having
      significantly higher values than females regardless of feeding type (P = 0.028
      and P < 0.001, respectively). CONCLUSION: There is no association between the use
      of palm olein formula during the first 4 months of life and subsequent bone
      mineral content and bone mineral density in healthy 4-year-old children.

PMID- 15990637
TI  - Type 2 diabetes in children is frequently associated with elevated alanine
      aminotransferase.
AB  - BACKGROUND: Nonalcoholic fatty liver disease, a cause of chronic liver disease in
      obese adults also occurs in obese children. In susceptible populations, fatty
      liver progresses to nonalcoholic steatohepatitis and eventually to fibrosis and
      cirrhosis. Nonalcoholic steatohepatitis is associated with elevation of alanine
      aminotransferase, although the aminotransferases can also be normal. The
      prevalence of nonalcoholic fatty liver disease in type 2 diabetes is unclear in
      adults and unknown in children. OBJECTIVES: The aim of this study was to estimate
      the prevalence of elevated serum aminotransferases as a marker of nonalcoholic
      fatty liver disease in pediatric type 2 diabetes and to identify correlates of
      aminotransferase elevation. METHODS: A chart review was completed on 115 children
      with type 2 diabetes at a pediatric diabetes clinic. The prevalence of elevated
      alanine aminotransferase was calculated from the 42% of patients with available
      aminotransferase measurements and correlations with fasting lipids, hemoglobin A
      1c, body mass index, age and diabetes therapy were sought. RESULTS: The
      prevalence of elevated alanine aminotransferase was 48%. There was no association
      between elevations and other variables. Among subjects with elevated alanine
      aminotransferase, 39% were one to two times above normal, 26% were two to three
      times normal and 35% were greater than three times above normal. Several patients
      experienced improvement in aminotransferase elevations after using insulin
      sensitizing medications. CONCLUSIONS: There is a high prevalence of elevated
      serum aminotransferases among children with type 2 diabetes unrelated to age,
      body mass index, glycemic control, blood lipids or diabetic therapy. The
      significance of this abnormality and its relationship to nonalcoholic fatty liver
      disease requires further evaluation.

PMID- 15990638
TI  - Intracranial vascular abnormalities in patients with Alagille syndrome.
AB  - OBJECTIVES: To define the spectrum of intracranial events and cerebrovascular
      lesions in patients with Alagille syndrome using magnetic resonance imaging with
      angiography of the head and medical histories and to correlate the presence of
      lesions with the clinical outcome of bleeding or ischemic intracranial events.
      METHODS: 26 patients with Alagille syndrome underwent magnetic resonance imaging
      with angiography of the head; 22 had no symptoms and underwent study for
      screening purposes and 4 were symptomatic with neurologic changes. The results of
      studies and the history of ischemic intracranial events were reviewed. RESULTS:
      Cerebrovascular abnormalities were detected in 10 of 26 (38%) patients (9 by head
      magnetic resonance imaging with angiography and 1 by necropsy). The findings
      included stenoses of the internal carotid arteries unilaterally (n = 5) or
      bilaterally (n = 3), basilar artery aneurysm (n = 1) and middle cerebral artery
      aneurysm (n = 1). Among the 9 patients with cerebrovascular abnormalities
      detected by magnetic resonance imaging with angiography, 5 had no symptoms (23%,
      5 of 22) and 4 were symptomatic. Thus, 100% of symptomatic patients had detected
      abnormalities and 23% of screened, asymptomatic patients had detected anomalies.
      Screening magnetic resonance imaging with angiography failed to detect vascular
      anomalies in 2 asymptomatic patients who had fatal ischemic intracranial events
      years later. There was evidence of progression of vascular abnormalities in 4
      patients. Ischemic intracranial events occurred in 10 of 26 (38%) patients and
      were associated with cerebrovascular abnormalities in 6 of 10 patients.
      CONCLUSION: The cerebral vasculopathy of Alagille syndrome predominantly involves
      the internal carotid arteries. It is more prevalent than would be suggested by
      the number of symptomatic individuals, appears to be progressive and shares many
      similarities with moyamoya. Magnetic resonance imaging with angiography is useful
      to detect these lesions and may have a valuable role in screening for treatable
      lesions such as aneurysms.

PMID- 15990639
TI  - Reduced bile flow associated with parenteral nutrition is independent of oxidant
      load and parenteral multivitamins.
AB  - BACKGROUND: Reduction in bile flow is a characteristic of cholestasis related to
      parenteral nutrition. Light exposure of parenteral multivitamin preparations is
      the major source of peroxides contaminating parenteral nutrition solutions. They
      may contribute to local oxidative stress. Oxidants are reported to affect
      transport mechanisms across the hepatocyte membrane into bile. The authors
      hypothesize that an oxidant-antioxidant imbalance is involved in parenteral
      nutrition related cholestasis. The aim of this study was to investigate the roles
      of multivitamin preparations and peroxides on bile flow in newborn guinea pigs
      receiving parenteral nutrition. METHODS: Three-day-old guinea pigs were fed
      enterally or parenterally with solutions containing 8% dextrose/0.45% NaCl +/-
      multivitamin preparation +/- amino acids +/- lipids. The influence of the oxidant
      antioxidant balance on bile flow was evaluated using 500 microM hydrogen peroxide
      and 1% and 3% multivitamin preparations +/- Na metabisulfite. Four days later,
      animals were anesthetized and bile flow was recorded over 2 hours. Glutathione
      determinations were performed on bile and liver samples. The percentage of
      oxidized glutathione, reflecting the redox status, was used as a marker of
      oxidative stress. Data were compared by analysis of variance with P < 0.05.
      RESULTS: Bile flow decreased first on initiating dextrose + NaCl infusion (a 25%
      decrease) and subsequently by adding amino acids (a further 30% decrease).
      Although antioxidant vitamins and peroxides modified the hepatic redox status,
      they did not influence bile flow. CONCLUSION: Although the composition of
      parenteral nutrition affects bile flow and the hepatic redox status, the oxidant
      antioxidant imbalance in infused solutions is not the causal event in the
      installation of cholestasis.

PMID- 15990640
TI  - Molecular characterization of a Portuguese patient with Shwachman-Diamond
      syndrome.

PMID- 15990641
TI  - SMAD4 germinal mosaicism in a family with juvenile polyposis and hypertrophic
      osteoarthropathy.

PMID- 15990642
TI  - Relative elevations of serum alanine and aspartate aminotransferase in muscular
      dystrophy.

PMID- 15990643
TI  - Mycophenolate mofetil in the management of alloimmune hemolytic anemia in ABO
      compatible but non-identical pediatric liver transplantation.

PMID- 15990644
TI  - Familial pyloric stenosis associated with developmental delays.

PMID- 15990645
TI  - Clinical quiz: Helicobacter pylori gastroduodenitis.

PMID- 15990646
TI  - Perianal presentation of Langerhans cell histiocytosis in children.

PMID- 15990647
TI  - C-ANCA/PR-3 positive colitis may be a distinctive form of inflammatory bowel
      disease.

PMID- 15990649
TI  - Evaluating the AIH scoring system.

PMID- 15990650
TI  - Worm therapy for ulcerative colitis: a possible link to regulatory T cells.

PMID- 15990651
TI  - The effect of autologous fibrin tissue adhesive on postoperative cerebrospinal
      fluid leak in spinal cord surgery: a randomized controlled trial.
AB  - STUDY DESIGN: A prospective randomized study evaluating the efficacy of
      autologous fibrin tissue adhesive for decreasing postoperative cerebrospinal
      fluid (CSF) leak in spinal cord surgery. OBJECTIVE: To compare postoperative CSF
      leak in 3 groups (i.e., autologous fibrin tissue adhesive used, commercial fibrin
      glue used, and no fibrin tissue adhesive used) of patients undergoing spinal
      surgery who needed dural incision. SUMMARY OF BACKGROUND DATA: Spinal cord
      operations, particularly when dural incision is inevitable, sometimes involve
      postoperative CSF leak. Because CSF leak is a serious complication,
      countermeasure is necessary to prevent it after dural suture. Commercial fibrin
      tissue adhesive was formerly used. Because the possibility of prion infection was
      widely noticed, commercial fibrin tissue adhesive containing animal components
      has been used less often. METHODS: In 13 of 39 cases in which dural incision
      would be made, 400 mL whole blood was drawn, and autologous fibrin tissue
      adhesive was made of plasma. Cases were divided into 3 groups: (1) dural closure
      alone, (2) use of autologous fibrin tissue adhesive after dural closure, and (3)
      use of commercial fibrin tissue adhesive after dural closure. The primary outcome
      measure was determined as postoperative (3 days) volume of drainage fluid, and
      results were analyzed using the analysis of variance. The secondary outcome
      measure was general blood test, coagulation assay, and plasma fibrinogen, and
      these were analyzed also using the analysis of variance. RESULTS: There was a
      significant difference in the primary outcome between the autologous and control
      groups. No complications such as infection or continuous CSF leak were observed
      in any case. The mean volume of drainage fluid was 586.2 mL in the group with
      autologous fibrin tissue adhesive and 1026.1 mL in the group without fibrin
      tissue adhesive. The volume of drainage fluid was significantly lower in the
      former group than that in the latter group. There was no statistical difference
      between the volumes of the group with autologous adhesive and with commercial
      adhesive (639.2 mL). CONCLUSIONS: We used autologous fibrin tissue adhesive as a
      new sealant after dural closure instead of commercial fibrin tissue adhesive. No
      definitive CSF leak was observed, and the volume of drainage fluid was
      significantly lower in the group with autologous fibrin tissue adhesive than that
      in the group without fibrin tissue adhesive. The use of autologous fibrin tissue
      adhesive was superior to that of commercial fibrin tissue adhesive in cost.

PMID- 15990652
TI  - Comparative biomechanical testing of anterior and posterior stabilization
      procedures.
AB  - STUDY DESIGN: This is a comparative in vitro biomechanical study in a calf lumbar
      spine model. OBJECTIVES: The objective was to compare the primary stability of an
      anterior instrumentation, an intercorporal cage in combination with an anterior
      instrumentation, and a posterior instrumentation for monosegmental spondylodesis.
      SUMMARY OF BACKGROUND DATA: Spondylodesis can be achieved through a posterior
      lumbar fusion, posterior lumbar intercorporal fusion, or an anterior lumbar
      intercorporal fusion. The posterior lumbar fusion is the gold standard, although
      the anterior approach offers some potential advantages to the transpedicular
      posterior techniques. METHODS: Stability testing was performed on 30 calf lumbar
      spine motion segments in a physiologic state (n = 30), with either an isolated
      anterior (MACS) or posterior instrumentation (SOCON), and with an anterior
      instrumentation augmented with an intercorporal cage (MACS-Cage, n = 10,
      respectively). Range of motion, neutral zone, and bending stiffness were measured
      under pure bending to 10 Nm, and bending stiffness under axial loads of up to
      1500 N. RESULTS: The isolated posterior instrumentation was found to be more
      stable than the isolated or augmented anterior instrumentation in
      flexion/extension, although no significant differences were observed in lateral
      bending or axial rotation. The results of this biomechanical study suggest that
      an augmented anterior instrumentation provides similar stability for bony fusion
      as does the golden standard posterior instrumentation, with the exception of
      flexion/extension. CONCLUSION: An augmented anterior instrumentation may provide
      similar stability for bony fusion as does the posterior instrumentation.

PMID- 15990653
TI  - Neck/shoulder disorders in a general population. Natural course and influence of
      physical exercise: a 5-year follow-up.
AB  - STUDY DESIGN: A 5-year follow-up study was conducted of men and women seeking
      care for new incidents of neck/shoulder disorders (NSD). OBJECTIVES: To study the
      natural course of pain and disability caused by NSD during a 5-year follow-up and
      to investigate the possible influence of regular physical exercise on recovery.
      SUMMARY OF BACKGROUND DATA: NSD are a major health problem, but their natural
      course is not very well studied. Several studies have investigated the role of
      physical exercise on NSD, with inconsistent results. METHODS: At baseline, a
      total of 439 subjects seeking care for NSD completed a questionnaire, and were
      interviewed about personal, medical, and occupational history, as well as
      physical exercise during leisure time. Over 5 years, 4 follow-up assessments were
      made by postal questionnaire. At all measuring points, pain intensity ratings and
      disability scores were compared between men and women, and between 3 exercise
      categories. RESULTS: The highest improvements in pain and disability, both in men
      and in women, were seen after 3 months. After that, only minor improvements were
      seen. In some cases, there was deterioration. However, after 5 years, both men
      and women had significant improvements, men more than women. Only the women were
      analyzed concerning physical exercise and were pooled into 3 categories according
      to intensity of exercise. There were no differences in changes in pain intensity
      and disability scores from baseline between the groups. CONCLUSIONS: A gender
      difference was seen in the change of pain and disability, with men having higher
      improvement than women over 5 years. Self-reported physical exercise of any
      intensity was not associated with higher recovery in women.

PMID- 15990654
TI  - Complete osteolysis of the dens with atlantoaxial luxation caused by infection
      with Staphylococcus aureus: a case report and review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To present a case of complete osteolysis
      of the dens and accompanying luxation of the atlantoaxial joint, on the basis of
      a Staphylococcus aureus infection. SUMMARY OF BACKGROUND DATA: To date, complete
      osteolysis of the dens followed by atlantoaxial dislocation has only been
      reported as a rare complication in patients with tuberculosis but not as
      secondary to a Staphylococcus aureus infection. METHODS: Because of emerging
      neurological complications in both upper extremities, we chose closed reduction
      and temporary Halo-fixation together with appropriate antibiotic coverage as
      primary treatment followed by an operative stabilization with Magerl fusion
      (Galli fusion combined with transarticular screw fixation of C1 and C2). RESULTS:
      After the operative procedure (Magerl fusion), immediate pain relief was achieved
      as well as almost complete resolution of neurological deficits. CONCLUSIONS: To
      our knowledge, this presents the first reported case of a complete destruction of
      the dens, as a result of a purulent bacterial infection leading to atlantoaxial
      luxation. Our case demonstrates that infections of the atlantoaxial region are
      difficult to diagnose and are seen mostly in immunocompromised patients, such as
      patients with diabetes. Furthermore, it proves that other infections besides
      tuberculosis can lead to complete osteolytic destruction of the atlantoaxial
      joint.

PMID- 15990655
TI  - Irreducible anterior atlantoaxial dislocation: one-stage treatment with a
      transoral atlantoaxial reduction plate fixation and fusion. Report of 5 cases and
      review of the literature.
AB  - STUDY DESIGN: Retrospective report of five surgical cases and review of the
      literature. OBJECTIVES: To report the clinical application of a novel internal
      fixation device in the treatment of irreducible atlantoaxial dislocation with
      ventral spinal cord compression. SUMMARY AND BACKGROUND DATA: Irreducible
      atlantoaxial dislocation with ventral spinal cord compression is difficult to
      treat. Traction is not uniformly successful at either reducing the dislocation or
      decompressing the spinal cord. Direct anterior decompression of the spinal cord
      may be necessary, in addition to the need for surgical stabilization of the upper
      cervical spine. Numerous methods have been described for surgical stabilization
      following transoral decompression, which generally require a second-stage
      posterior instrumentation and fusion procedure. Complication rates remain
      noteworthy for any of these strategies. METHODS: A novel transoral atlantoaxial
      reduction plate (TARP) system was designed to facilitate a one-stage anterior
      operation capable of simultaneously decompressing the ventral spinal cord as well
      as reducing and fusing the atlantoaxial segment. The procedure and TARP implant
      has been employed for five patients with irreducible atlantoaxial dislocation
      because of trauma or congenital disorders. Following transoral decompression and
      excision of scar, ligament and osteophytes, the TARP was used to affect reduction
      and fixation of the atlantoaxial joints. The decorticated atlantoaxial joint
      surfaces were grafted with autogenous iliac crest bone. The histories of these
      cases were reported in detail. RESULTS: The five case examples demonstrate the
      efficacy of this one-stage approach to the surgical treatment of irreducible
      anterior atlantoaxial dislocation with spinal cord compression. The role of the
      TARP in affecting and maintaining the reduction while promoting successful fusion
      is illustrated. CONCLUSION: The authors' one-stage anterior procedure employing
      their TARP for the surgical treatment of irreducible anterior atlantoaxial
      subluxation was effective in these five cases. This method was able to avoid the
      need for interval traction and/or a second stage posterior instrumentation and
      fusion procedure.

PMID- 15990656
TI  - Positive effect of posterior instrumentation after surgical posterior
      decompression for extensive cervicothoracic ossification of the posterior
      longitudinal ligament.
AB  - STUDY DESIGN: A case report of a 55-year-old patient with extensive
      cervicothoracic ossification of the posterior longitudinal ligament (OPLL) that
      was treated with posterior decompression and fusion. OBJECTIVE: To report the
      preventive effect of posterior instrumentation on postoperative paralysis in
      extensive cervicothoracic OPLL. SUMMARY OF BACKGROUND DATA: Thoracic myelopathy
      caused by OPLL in the thoracic spine was treated with operative decompression of
      the spinal cord via an anterior, posterior, or posterolateral approach. However,
      the lack of availability for some approaches in specific cases, as well as
      reports of some problems for each approach, indicates that a lack of consensus
      still remains regarding the choice of operative procedure. METHODS: A 55-year-old
      female with extensive cervicothoracic OPLL presented with progressive numbness in
      the both hands and a gate disturbance. Cervical laminoplasty, thoracic
      laminectomy, and posterior fusion were performed with electrophysiologic
      monitoring of the spinal cord evoked potential. RESULTS: After thoracic
      laminectomy, the amplitude of spinal cord evoked potential waveforms decreased
      but recovered after a posterior fusion by instrumentation. CONCLUSION: Prevention
      of postoperative paralysis from increasing by posterior instrumentation was shown
      using neurophysiologic monitoring.

PMID- 15990658
TI  - Manohar M. Panjabi: the sixth ISSLS Wiltse Lifetime Achievement Award sponsored
      by Stryker recipient.

PMID- 15990659
TI  - Frequency and clinical predictors of adverse reactions to chiropractic care in
      the UCLA neck pain study.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To document the types and
      frequencies of adverse reactions associated with the most common chiropractic
      treatments for neck pain, and to identify possible clinical predictors of adverse
      reactions to chiropractic treatment. SUMMARY OF BACKGROUND DATA: Chiropractic
      care is frequently sought by patients for relief from neck pain; however, adverse
      reactions related to its primary modes of treatment have not been well examined.
      METHODS: A total of 336 patients with neck pain presenting to 4 southern
      California health care clinics were randomized in a balanced 2 x 2 x 2 factorial
      design to manipulation with or without heat, and with or without electrical
      muscle stimulation (EMS); and mobilization with or without heat and with or
      without EMS. Discomfort or unpleasant reactions from chiropractic care were self
      assessed at 2 weeks after the randomization/baseline visit. RESULTS: Of the 280
      participants (83%) who responded, 85 (30.4%) had 212 adverse symptoms as a result
      of chiropractic care. Increased neck pain or stiffness was the most common
      symptom, reported by 25% of the participants. Less common were headache and
      radiating pain. Patients randomized to manipulation were more likely than those
      randomized to mobilization to have an adverse symptom occurring within 24 hours
      of treatment (adjusted odds ratio [OR] = 1.44, 95% confidence interval [CI] =
      0.83, 2.49). Heat and EMS were only weakly associated with adverse symptoms
      (heat: OR = 0.94, 95% CI = 0.54, 1.62; EMS: OR = 1.09, 95% CI = 0.63, 1.89).
      Moderate-to-severe neck disability at baseline was strongly associated with
      adverse neurologic symptoms (OR = 5.70, 95% CI = 1.49, 21.80). CONCLUSIONS: Our
      results suggest that adverse reactions to chiropractic care for neck pain are
      common and that despite somewhat imprecise estimation, adverse reactions appear
      more likely to follow cervical spine manipulation than mobilization. Given the
      possible higher risk of adverse reactions and lack of demonstrated effectiveness
      of manipulation over mobilization, chiropractors should consider a conservative
      approach for applying manipulation to their patients, especially those with
      severe neck pain.

PMID- 15990660
TI  - Trabecular architecture of lumbar vertebral pedicle.
AB  - STUDY DESIGN: Investigation on architecture of lumbar pedicle. OBJECTIVE: To
      determine morphological properties of pedicular cancellous bone. SUMMARY OF
      BACKGROUND DATA: Many researchers have been stimulated to study trabecular
      architecture by improvements in stereological technology. Although the structure
      of vertebral cancellous bone has been well studied in the literature, no
      information is available about the architecture of pedicular cancellous bone.
      METHODS: Eight cadaveric L3 lumbar vertebrae were harvested. After collecting the
      bone mineral density (BMD) data on the vertebrae, pedicle isthmuses were removed
      from the vertebral bodies using a reciprocal hand saw. The BMD measurements were
      done on the dissected pedicle isthmus specimens. All the specimens were then
      analyzed using a micro-computed tomography unit. Morphologic parameters of
      trabecular bone were calculated. RESULTS: Bone volume was found as 0.209 +/-
      0.046, whereas Tb.Th, Tb.Sp, and Tb.N were found to be 0.201 +/- 0.035 mm, 0.930
      +/- 0.123 mm, and 1.098 +/- 0.136 mm(-1), respectively. Connectivity density and
      structure model index were observed to be 3.135 +/- 0.918 mm(-3), 0.37, whereas
      degree of anisotropy value was 1.241 +/- 0.093. Vertebral BMD could explain 63%
      of variance in bone density of a pedicle isthmus. CONCLUSIONS: The structure of
      the pedicular cancellous bone is somewhat different from that of vertebral body.
      The trabecular architecture within the pedicle isthmus is isotropic and plate
      like. The thickness and number of the trabeculae were greater than those of
      vertebral trabeculae. Decrease in the bone volume with age is mainly by thinning
      of the trabeculae and increasing in trabecular spacing, but not by loss of mass.

PMID- 15990661
TI  - Effects of growth hormone transgene expression on vertebrae in a mouse model of
      osteogenesis imperfecta.
AB  - STUDY DESIGN: A human growth hormone transgene was bred into mice of the Cola2oim
      (oim) lineage. Caudal (tail) vertebrae from male and female mice at early
      skeletal maturity and at midlife were evaluated for physical and biomechanical
      properties. OBJECTIVE: To test whether constant low-level growth hormone
      expression within the marrow could improve structural or material properties of
      caudal vertebrae in oim mice. SUMMARY OF BACKGROUND DATA: A spontaneous genetic
      defect in a type I procollagen gene created the oim mouse model for osteogenesis
      imperfecta. Bones of heterozygous oim mice are biomechanically inferior to wild
      type controls. Bone marrow expression of human growth hormone was demonstrated
      previously to enhance bone deposition and structural biomechanical properties in
      caudal vertebrae of transgenic mice. METHODS: Compression tests were performed
      individually on three caudal vertebrae (Ca4, 5, and 6) from each mouse to
      determine their structural biomechanical properties. Volumetric and mineral
      content measurements were also made. In a subset of vertebrae, the ashing
      measurements were confirmed and extended by peripheral quantitative tomographic
      scanning, which also allowed calculation of the failure stress. RESULTS:
      Heterozygous oim mouse vertebrae had structural and material properties inferior
      to the wild-type controls. Growth hormone transgene expression increased the size
      and mineral content of the vertebrae from mutant mice, and increased
      biomechanical structural values for maximum load and energy to failure. Failure
      stress was not improved. CONCLUSIONS: Growth hormone stimulation of size and bone
      mineral content of osteogenesis imperfecta mutant mouse caudal vertebrae
      contributed to their improved performance in axial compression. There was no
      evidence for improved material properties, however.

PMID- 15990662
TI  - Expression and co-expression of VR1, CGRP, and IB4-binding glycoprotein in dorsal
      root ganglion neurons in rats: differences between the disc afferents and the
      cutaneous afferents.
AB  - STUDY DESIGN: The expression of vanilloid receptor 1 (VR1), calcitonin gene
      related peptide (CGRP), and isolectin B4 (IB4)-binding glycoprotein in dorsal
      root ganglion (DRG) neurons innervating the lumbar disc and the plantar skin was
      investigated. OBJECTIVE: To characterize the DRG neurons innervating lumbar discs
      and those innervating cutaneous tissue in rats. SUMMARY AND BACKGROUND DATA:
      Small nociceptive DRG neurons are divided into nerve growth factor (NGF)
      sensitive and glial cell line-derived neurotrophic factor (GDNF)-sensitive
      neurons. CGRP and IB4-binding glycoprotein are recognized as specific markers for
      NGF and GDNF-sensitive neurons, respectively. VR1 is localized in small DRG
      neurons. METHODS: Using histochemical staining and retrograde tracing methods,
      the expression of VR1, CGRP, and IB4-binding glycoprotein in DRG neurons
      innervating the L5-L6 disc and the plantar skin was examined in rats. RESULTS:
      DRG neurons innervating the disc showed positive staining as: 23.4% VR1, 54.4%
      CGRP, and 1.0% IB4-binding glycoprotein. The following distribution was found for
      DRG neurons innervating the skin: 35.1% VR1, 41.1% CGRP, and 19.5% IB4-binding
      glycoprotein. Percentages of neurons positive for VR1 and IB4-binding
      glycoprotein were significantly lower in DRG neurons innervating the disc than in
      DRG neurons innervating the skin (P < 0.05), while no significant difference was
      observed in the percentage of neurons positive for CGRP. CONCLUSIONS: VR1 is less
      abundant in lumbar disc than in cutaneous tissue. Our data suggest that
      nociceptive information from the disc is transmitted mostly by NGF-sensitive
      neurons, while that from the cutaneous tissue is transmitted by both NGF
      sensitive and GDNF-sensitive neurons.

PMID- 15990663
TI  - Neovascularization and neoinnervation of subcutaneously placed nucleus pulposus
      and the inhibitory effects of certain drugs.
AB  - STUDY DESIGN: An experimental study in the pig with autologous transfer of
      nucleus pulpous and retroperitoneal fat to the subcutaneous space of the back.
      OBJECTIVES: To evaluate if there is neovascularization or neoinnervation of
      subcutaneously placed nucleus pulposus, in comparison to retroperitoneal fat, and
      under simultaneous treatment by certain antiangiogenetic drugs. SUMMARY OF
      BACKGROUND DATA: It has been suggested that intervertebral discs may be invaded
      by newly formed blood vessels and nerve fibers following injury of the anulus
      fibrosus. The nerve fibers have been considered to induce low back pain. However,
      it is still debated whether such ingrowth may occur and, if present, if this is
      based on the action of angiogenetic substances in the intervertebral disc or
      simply by normal would healing. METHODS: In the first series, autologous nucleus
      pulposus and retroperitoneal fat was placed subcutaneously in 3 pigs. In the
      second series, autologous nucleus pulposus was placed subcutaneously with
      simultaneous treatment with methotrexate (n = 3), celecoxib (n = 3), doxycycline
      (n = 3), and infliximab (n = 3). After 7 days, the tissue was collected and
      processed immunohistochemically for the visualization of blood vessels and nerve
      fibers. RESULTS: There was a number of blood vessels and nerve fibers in the
      nucleus pulposus samples, while no vessels were observed in the fat samples.
      Neither methotrexate nor celecoxib seemed to be able to reduce the ingrowth of
      blood vessels (neovascularization) or nerve fibers (neoinnervation). Treatment by
      doxycycline and infliximab markedly reduced both neovascularization and
      neoinnervation. CONCLUSIONS: Subcutaneously placed autologous nucleus pulposus
      displays an ingrowth of newly formed blood vessels and nerve fibers within 7
      days, in contrast to retroperitoneal fat. Such ingrowth seems to be reduced by
      doxycycline and infliximab, 2 cytokine inhibitors. The data suggest that the
      ingrowth may be induced by bioactive substances within the nucleus pulposus. The
      clinical importance of these data has yet to be elucidated.

PMID- 15990664
TI  - Biomechanics of stabilization after cervicothoracic compression-flexion injury.
AB  - STUDY DESIGN: Biomechanical laboratory research. OBJECTIVE: To determine whether
      anterior, posterior, or combined instrumentation provides the best stability for
      treating a cervicothoracic compression-flexion injury. SUMMARY OF BACKGROUND
      DATA: As the junction between the mobile cervical spine and rigid thoracic spine,
      the cervicothoracic junction poses unique challenges to the success of any
      fixation system spanning this region. Although posterior instrumentation is the
      preferred method of fixation in the unstable cervical spine, it is unknown
      whether this is the case across the unstable cervicothoracic junction. METHODS:
      Flexion, extension, lateral bending, and axial rotation of cadaveric specimens
      were studied during application of nondestructive pure moments in a sequence of
      conditions: (1) intact, (2) after destabilization, (3) with posterior
      instrumentation from C6-T1 or T2, and (4) with corpectomy/graft and anterior
      alone or combined anterior/posterior instrumentation. RESULTS: Compared to
      anterior instrumentation, posterior instrumentation allowed an 89% smaller range
      of motion (ROM) during lateral bending (P = 0.01) and 64% smaller ROM during
      axial rotation (P = 0.04). In most loading modes, combined instrumentation
      outperformed either anterior or posterior instrumentation alone. Most
      biomechanical measurements of stability improved when posterior instrumentation
      was extended from T1 to T2. Small and usually insignificant reductions in ROM
      averaging 15% were observed with C7 included in the posterior construct versus C7
      excluded. CONCLUSIONS: Combined instrumentation provides a significant
      improvement in stability over either anterior or posterior instrumentation alone.
      Extension of the posterior instrumentation to include T2 improves stability at T1
      T2 as well as rostral levels. Inclusion of C7 in the construct is largely
      inconsequential biomechanically.

PMID- 15990665
TI  - Constructs incorporating intralaminar C2 screws provide rigid stability for
      atlantoaxial fixation.
AB  - STUDY DESIGN: An in vitro biomechanical study of C1-C2 posterior fusion
      techniques using a cadaveric model. OBJECTIVES: To investigate the acute
      stability afforded across the atlantoaxial segment by a novel technique that uses
      intralaminar screws in C2, and to compare these results to the stability obtained
      using a C2 pedicle fixation technique. SUMMARY OF BACKGROUND DATA: There are
      numerous techniques available for rigidly coupling C1 and C2. It has been shown
      that screw techniques provide higher acute stability than wiring practices.
      However, many of these methods that use screw fixation in C2 can be technically
      difficult, especially in cases in which there is an aberrant vertebral artery
      course or if the C2 pedicle is not large enough to accommodate the
      instrumentation. A novel technique that uses intralaminar screws in C2 with C1
      pedicle screws and bilateral longitudinal rods has been recently developed in an
      effort to overcome many of these issues. To date, there are no published reports
      as to whether this new technique provides equivalent (or better) fixation to the
      currently accepted methods. METHODS: Six fresh-frozen human cadaveric cervical
      spines (C0-C4) were used in this study. Specimens were tested in their intact
      condition after destabilization via odontoidectomy, and after implantation of 3
      different fixation constructs: (1) the Harms technique, 2 pedicle screws in C2,
      (2) a single C2 pedicle screw and a single C2 intralaminar screw, and (3) a
      construct having bilateral intralaminar C2 screws. Pure moment loading in
      flexion/extension, lateral bending, and axial rotation was applied to the
      occiput. Subsequent relative intervertebral rotations were determined using a 3
      camera system. Range of motion for the intact, destabilized, and 3 fixation
      scenarios was determined, and statistical analysis was performed using one-way
      analysis of variance Fisher least-significant-difference post hoc test for
      multiple comparisons. RESULTS: The data indicate that odontoidectomy
      significantly increased C1-C2 motion in flexion/extension and lateral bending.
      All 3 fixation techniques significantly reduced motion compared to the intact and
      destabilized cases. There were no statistically significant differences between
      the C2 intralaminar and pedicle screw techniques. CONCLUSIONS: The results
      clearly indicate the potential of the intralaminar screw technique to provide
      stability that is equivalent to methods currently used. Given the serious
      complications that can follow vertebral artery injury and the decreased
      likelihood of injury by avoiding placement of C2 pedicle screw(s) and C1-C2
      transarticular screw(s), strong consideration should be given to using a
      construct that incorporates C2 intralaminar screw(s).

PMID- 15990666
TI  - Anatomic considerations for the pedicle screw placement in the first cervical
      vertebra.
AB  - STUDY DESIGN: Anatomic bony measurements were manually performed on 50 dry
      atlantoaxial vertebral complexes with an electronic digital caliper, and a
      reliable landmark for insertion of a pedicle screw in C1 vertebra was described
      and evaluated. OBJECTIVES: To investigate the feasibility of placing a screw in
      the C1 pedicle and evaluate the reliability of the C2 lateral mass as a landmark
      for determining the optimal site of screw entry. SUMMARY OF BACKGROUND DATA: The
      use of C1-C2 pedicle screws with the additional rods or plates has been an
      alternative method of stabilization for patients who are unsuitable for C1-C2
      transarticular screw stabilization. However, the optimal portal of entry for the
      C1 pedicle screw is difficult to determine during surgery in the absence of
      reliable reference landmarks and sufficient relevant anatomic studies. METHODS:
      We manually measured 11 linear anatomic parameters related to the C1 lateral
      mass, its pedicle and posterior arch under the groove on 50 pairs of dry C1-C2
      complexes harvested from cadavers. We also treated five patients with
      atlantoaxial instability with C1 and C2 pedicle screw fixation; the entry point
      of the C1 pedicle screw was ascertained by using C2 lateral mass as a landmark,
      and the position of the C1 pedicle screws in each case was evaluated with
      postoperative radiographs and computed tomography scans. RESULTS: The mean
      mediolateral width and rostrocaudal height of C1 pedicle were 8.57 and 5.83 mm,
      respectively. The mean rostrocaudal height of C1 posterior lamina at the
      reference entry point for the screw was 4.59 mm. The mean rostrocaudal height of
      the C1 posterior arch under the vertebral artery groove was 3.88 mm at its medial
      one-third and 4.25 mm at its lateral one-third. The thinnest external diameter of
      the screw tract that was recorded was <4 mm in six (12%) specimens of C1
      vertebrae. The center of C2 lateral mass was 1.51 mm lateral to the sagittal
      plane of the mediolateral midpoint of the C1 pedicle. The distance from the
      suggested screw entry point to C1 posterior tubercle was 22.15 mm, and the mean
      length of the screw tract was 28.55 mm. Ten C1 pedicle screws were placed
      exactly, without neural or vascular injury in all five patients. CONCLUSION: The
      heights of the C1 pedicle, the posterior arch under the groove and the posterior
      lamina at the screw entry point are the major determinants for the possibility of
      placing pedicle screws in C1 of a given patient. This study indicates that it is
      feasible to place a 3.5-mm pedicle screw safely in C1 in most patients, and the
      lateral mass of C2 is a reliable anatomic landmark that can be easily identified
      to help the surgeon determine the optimal screw entry portal conveniently during
      surgery.

PMID- 15990667
TI  - Cervical spine injuries in the elderly: acute postoperative mortality.
AB  - STUDY DESIGN: This study retrospectively reviewed 12 years of consecutive
      patients with cervical spine injuries. OBJECTIVE: To establish reasonable
      expectations for short-term postoperative survival of the elderly patient with a
      cervical spine injury. SUMMARY OF BACKGROUND DATA: Previous studies have outlined
      dismal expectations for patients older than 65 years, with cervical spine
      injuries. This result has led many surgeons to consider more conservative
      treatment when compared to younger patients with similar injuries. METHODS: A
      total of 458 patients treated surgically over a 12-year period at a single
      tertiary spine care center were reviewed. The patients were divided into 2 groups
      by age, older and younger than 65 years. Prospective data were collected from the
      time of admission to discharge from the acute care facility, and included age,
      injury etiology, anatomic and neurologic injury patterns, and morbidity and
      mortality RESULTS: There were 74 patients older than 65 years and 384 younger
      than 65 years who underwent surgical stabilization of their injury. The overall
      mortality rate during the initial hospitalization was 3.9%. The mortality rate of
      the elderly group was 12.2%, while 2.3% for the younger patients. Common
      postoperative morbidities in the older group included myocardial infarction, deep
      vein thrombosis, pulmonary emboli, and gastrointestinal bleeds. In the younger
      group, pneumonia, respiratory failure, and urinary tract infections were more
      frequent. CONCLUSIONS: The realistic expectation for short-term postoperative
      survival in the elderly patient with a cervical spine injury is 87.8%. With a
      complete neurologic injury, 80.0% short-term survival was observed. Incomplete
      neurologic injury yielded 83.3% short-term survival. Close to 100.0% survival can
      be expected with no neurologic injury.

PMID- 15990668
TI  - Correction of adolescent hyperkyphosis with posterior-only threaded rod
      compression instrumentation: is anterior spinal fusion still necessary?
AB  - STUDY DESIGN: Retrospective clinical and radiographic review. OBJECTIVE: To
      assess the need for anterior apical release and fusion before posterior threaded
      rod compression instrumentation and closing-wedge lamina resection for the
      treatment of adolescent hyperkyphosis. SUMMARY OF BACKGROUND DATA: Traditional
      treatment of adolescent hyperkyphosis has included a preliminary anterior release
      and fusion of apical disc segments to achieve and maintain better correction.
      METHODS: A total of 27 patients undergoing correction of adolescent hyperkyphosis
      with posterior threaded rod Texas Scottish Rite Hospital instrumentation was
      reviewed. Of the 27 patients, 19 had strict Sorensen criteria for Scheuermann
      kyphosis. There were 20 patients (group 1) who underwent posterior surgery only,
      while 7 (group 2) underwent same day preliminary open or endoscopic anterior
      release and fusion of 5-7 apical segments. A closing-wedge laminar resection was
      used to facilitate shortening of the posterior column. All but 2 patients were
      braced for up to 3 months after surgery. Preoperative, immediate postoperative,
      and final follow-up radiographs at 24-56 months postoperatively were analyzed for
      the amount and loss of correction of measured kyphosis, T2-T12 kyphosis, T10-L2
      kyphosis, T12-S1 lordosis, C7 plumbline sagittal balance, and correction of
      Voutsinas index. RESULTS: There was no difference in the amount of correction
      achieved at final follow-up between the 2 groups (group 1 = 53%, group 2 = 46%, P
      = 0.47). There was also no difference (P = 0.84) in the amount of correction
      immediately after surgery compared to final follow-up. No patient lost more than
      8 degrees correction after surgery. One asymptomatic rod fracture occurred, with
      no loss of correction, implying no pseudarthroses. Similarly, there were no
      differences in any of the other sagittal plane measurements between the 2 groups,
      except for Voutsinas index (VI) in which group 1 patients had better
      normalization (VI = 0.11) compared to group 2 (VI = 0.15, P =0.05). CONCLUSIONS:
      Traditional anterior/posterior fusion technique provides no additional
      improvement in radiographic outcome compared to posterior-only surgery for
      adolescent hyperkyphosis. Preliminary anterior release and fusion is no longer
      performed when correcting this deformity with a posterior column shortening
      procedure and threaded rod compression instrumentation.

PMID- 15990669
TI  - Center of gravity and radiographic posture analysis: a preliminary review of
      adult volunteers and adult patients affected by scoliosis.
AB  - STUDY DESIGN: This is a prospective radiographic and force plate analysis
      involving adult volunteer and patients with scoliosis. OBJECTIVE: To assess
      accurately the center of pressure in standing volunteers and patients with
      scoliosis, and correlate these finding with radiographic data. SUMMARY OF
      BACKGROUND DATA: A simple and commonly applied parameter of global balance is the
      plumbline offset. This radiographic measurement refers to the center of C2 (or
      C7) drawn vertically downward. Although this measurement is simple, it may not
      accurately reflect the balance of the spine. METHODS: This study included adult
      volunteers (n = 41) and patients with scoliosis (n = 45). Full-length,
      freestanding spine radiographs were obtained with subjects on a force plate.
      Simultaneous assessment of the radiologic spinal posture and the floor projection
      of the center of pressure (gravity line) was possible. The latter was projected
      on the full spine images and correlated to common radiographic parameters.
      RESULTS: The position of the gravity line differed significantly from the
      plumbline in frontal and sagittal planes (P < 0.001). This difference was
      maintained in both study populations. The mean frontal plane alignment of the
      gravity line was consistently to the right of the plumbline. The mean sagittal
      plane alignment of the gravity in relation to the plumbline revealed an offset
      anteriorly. CONCLUSIONS: The data analysis of offsets between the gravity line
      and radiographic parameters revealed a frontal plane mean displacement of the
      gravity line to the right. In the sagittal plane, a highly significant lack of
      correlation between the gravity line and plumbline was noted. The plumbline
      represents a common and convenient visual display of apparent sagittal plane
      imbalance, but its value as a marker of true postural balance must be questioned.

PMID- 15990670
TI  - Three-year incidence of low back pain in an initially asymptomatic cohort:
      clinical and imaging risk factors.
AB  - STUDY DESIGN: Prospective cohort study of randomly selected Veterans Affairs out
      patients without baseline low back pain (LBP). OBJECTIVE: To determine predictors
      of new LBP as well as the 3-year incidence of magnetic resonance imaging (MRI)
      findings. SUMMARY OF BACKGROUND DATA: Few prospective studies have examined
      clinical and anatomic risk factors for the development of LBP, or the incidence
      of new imaging findings and their relationship to back pain onset. METHODS: We
      randomly selected 148 Veterans Affairs out-patients (aged 35 to 70) without LBP
      in the past 4 months. We compared baseline and 3-year lumbar spine MRI. Using
      data collected every 4 months, we developed a prediction model of back pain-free
      survival. RESULTS: After 3 years, 131 subjects were contacted, and 123 had repeat
      MRI. The 3-year incidence of pain was 67% (88 of 131). Depression had the largest
      hazard ratio (2.3, 95% CI = 1.2-4.4) of any baseline predictor of inci-dent back
      pain. Among baseline imaging findings, central spinal stenosis and nerve root
      contact had the highest, though nonsignificant, hazard ratios. We did not find an
      association between new LBP and type 1 endplate changes, disc degeneration,
      annular tears, or facet degeneration. The incidence of new MRI findings was low,
      with the most common new finding being disc signal loss in 11 (9%) subjects. All
      five subjects with new disc extrusions and all four subjects with new nerve root
      impingement had new pain. CONCLUSION: Depression is an important predictor of new
      LBP, with MRI findings likely less important. New imaging findings have a low
      incidence; disc extrusions and nerve root contact may be the most important of
      these findings.

PMID- 15990672
TI  - Risk factors for musculoskeletal symptoms and ensuing health care use and sick
      leave.
AB  - STUDY DESIGN: Longitudinal study with a 6-month follow-up. OBJECTIVE: To
      investigate whether demographic, work-related physical and psychosocial risk
      factors involved in the occurrence of musculoskeletal symptoms also determine
      subsequent health care use and sick leave. SUMMARY OF BACKGROUND DATA: Preventing
      the socioeconomic consequences of disability from musculoskeletal symptoms may be
      a goal separate from that of eliminating the symptoms themselves; thus, other
      factors may need to be addressed in intervention. METHODS: A questionnaire
      provided data on demographics and work-related factors, musculoskeletal symptoms,
      and ensuing health care use and sick leave among 407 industrial workers. RESULTS:
      The 12-month prevalence of low back pain (LBP) and neck/upper extremity symptoms
      was 52% and 56%, respectively. Of those individuals with symptoms at baseline,
      68% had a recurrence of LBP, and 62% a recurrence of neck/upper extremity
      symptoms during a 6-month follow-up. The recurrence of sick leave for a
      particular musculoskeletal complaint was approximately 30%, while recurrence of
      health care use was more than 40%. Recurrence of symptoms, health care use, and
      sick leave were strongly associated with a history of severe symptoms. Physical
      load, high job strain, and low social support at work determined the occurrence
      of LBP, related health care use, and sick leave. Older age and living alone were
      also important risk factors, especially for sick leave. High job strain
      determined the occurrence of neck/upper extremity symptoms, related health care
      use, and sick leave. Being female and living alone increased the probability of
      the occurrence of all 3 endpoints, especially the occurrence of sick leave.
      CONCLUSIONS: Work-related factors that were associated with the occurrence of
      musculoskeletal symptoms were quite similar to those associated with health care
      use and sick leave. However, for LBP, older age and living alone, and, for
      neck/upper extremity symptoms, living alone and being female more strongly
      determined whether subjects with these complaints took sick leave. These results
      imply that prevention strategies aimed at minimizing the risks of the occurrence
      of work-related musculoskeletal symptoms and prevention programs aimed at
      reducing sick leave may need to emphasize different sets of risk factors.

PMID- 15990674
TI  - Case report: Whiplash-associated disorder from a low-velocity bumper car
      collision: history, evaluation, and surgery.

PMID- 15990675
TI  - Classification of the normal variation in the sagittal alignment of the human
      lumbar spine and pelvis in the standing position.

PMID- 15990676
TI  - Spinal cord infarction following therapeutic computed tomography-guided left L2
      nerve root injection.

PMID- 15990679
TI  - Placental leucine aminopeptidase might regulate the effects of oxytocin with
      resolution in endothelial cells.
AB  - BACKGROUND: Oxytocin (OT) is known to cause vascular relaxation via nitric oxide
      (NO) production and proliferation of endothelial cells. Previously we revealed
      that human umbilical vascular endothelial cells (HUVECs) expresses placental
      leucine aminopeptidase (P-LAP)/insulin regulated aminopeptidase (IRAP), which
      becomes translocation to the cell surface on activation of oxytocin receptor
      (OTR). However, the physiological roles of P-LAP in HUVECs have not been
      elucidated. MATERIAL/METHODS: Actions of OT on HUVECs transfected with a copy of
      the human P-LAP gene were therefore examined with a focus on changes in
      parameters linked to OTR such as calcium mobilization, NO production and cell
      proliferation. RESULTS: Cell surface P-LAP activity was significantly elevated
      (approximately 3 fold) in P-LAP overexpressing-HUVECs and overexpression of P-LAP
      resulted in remarkable inhibition of OT effects on HUVECs such as cell
      proliferation, [Ca2+]i, and NO production. CONCLUSIONS: These findings suggested
      that P-LAP on the plasma membrane in HUVECs regulates the effects of OT with
      resolution around OTR.

PMID- 15990678
TI  - MSG-1 expression in benign and malignant melanocytic lesions of cutaneous and
      mucosal epithelium.
AB  - BACKGROUND: A more recently characterized melanocyte-specific gene, MSG-1, has
      been suggested as having a role in embryogenesis, melanogenesis and melanoma
      progression. Studies involving MSG-1 have involved cutaneous melanocytic lesions,
      which are different than non-cutaneous melanocytic lesions in certain
      pathogenetic aspects. The purpose of this study was to evaluate MSG-1 protein
      expression in cutaneous and mucosal melanocytic lesions, with the aim to explore
      its association with pigment production, malignant potential and UV light
      exposure. MATERIAL/METHODS: Benign and malignant melanocytic lesions of cutaneous
      and mucosal epithelium were selected from our pathology registry (n=48).
      Immunohistochemistry was performed using polyclonal anti-MSG-1 antibody and
      standard streptavidin-biotin immunoperoxidase techniques. The staining pattern of
      MSG-1 was evaluated by three pathologists independently. RESULTS: MSG-1 protein
      demonstrated immunoreactivity in only one mucosal melanoma (1/20, 5%), arising in
      the lower lip, and showing histopathologic evidence of sun-induced tissue damage.
      MSG-1 also showed positivity in five cutaneous melanomas (5/14, 36%), one of
      which was a metastatic lesion. All mucosal and cutaneous nevi failed to express
      MSG-1. Melanin pigmentation, seen in 18/34 melanoma and 13/14 nevi, did not
      correlate with MSG-1 expression. All cases but one showing MSG-1 immunoreactivity
      were located in sun-exposed sites. CONCLUSIONS: The finding of MSG-1 expression
      in some cases of malignant melanoma, and its absence in all benign nevi, may
      indicate an association with melanoma progression, particularly UV-induced
      lesions. Its infrequent expression in melanocytic lesions limits its diagnostic
      value as an immunohistochemical marker in routine pathology practice.

PMID- 15990680
TI  - Liquid-liquid systems for acid hydrolysis of glycoalkaloids from Solanum
      tuberosum L. tuber sprouts and solanidine extraction.
AB  - BACKGROUND: Potato sprouts (Solanum tuberosum L.) contain steroidal
      glycoalkaloids containing solanidine, an important precursor for hormone
      synthesis. Glycoalkaloids are reported to inactivate the Herpes simplex, Herpes
      zoster and Herpes genitalis viruses in humans, while Aglyones, including
      solasodine, may protect against skin cancer. Extracts of glycoalkaloids or
      solanidine can be used to obtain a potential skin cancer preparation for clinical
      research. MATERIAL/METHODS: Dried potato sprouts were used to obtain
      glycoalkaloids and solanidine. The hydrolysis of glycoalkaloids in a liquid
      liquid system was performed using a reflux condenser, obtaining extracts of
      glycolakaloids from dried and milled potato tuber sprouts. Hydrochloric acid was
      then added to the extract to form the first (aqueous) phase, and chloroform,
      trichloroethylene or carbon tetrachloride to form the second (organic) phase of
      the liquid-liquid system. In this way, glycoalkaloid hydrolysis to solanidine and
      solanidine extraction in the organic liquid phase were combined into a single
      step. IR and GC/MS analysis of solanidine was also conducted. RESULTS: Based on
      the results we obtained, the optimal liquid-liquid system was found to be 2% w/v
      hydrochloric acid in a 50% (volume) methanolic extract of glycoalkaloids from
      tuber sprouts, as the first phase, and chloroform as the second phase. Using this
      system, a yield of 1.46 g solanidine per 100 g of dried potato sprouts can be
      achieved. CONCLUSIONS: Glycoalkaloid hydrolysis in a liquid-liquid system yields
      the aglycone solanidine can be obtained from dried potato sprouts. The yield of
      solanidine is higher than that obtained using solid-liquid-liquid systems for
      glycoalkaloid hydrolysis from potato vines.

PMID- 15990681
TI  - Insulin treatment decreases the antioxidant defense mechanism in experimental
      diabetes.
AB  - BACKGROUND: Hyperglycemia-induced oxidative stress and left ventricular
      hypertrophy is an independent risk factor for cardiovascular disease. Our aim was
      to determine the relationship between left ventricular hypertrophy and the total
      scavenger capacity (TSC) in diabetic rats. MATERIAL/METHODS: Control animals
      (n=30) were compared to streptozotocin-induced diabetic rats (n=38) and diabe-tic
      rats receiving insulin treatment (n=30) for 22 days. Half of the animals received
      angiotensin II on day 21. The left ventricular mass, TSC and carbohydrate
      parameters were determined. RESULTS: Diabetes did not alter left ventricular
      mass; however, diabetes with insulin treatment was associated with left
      ventricular hypertrophy. The extent of ventricular hypertrophy did not change
      significantly in this group after angiotensin II treatment. TSC increased very
      significantly in diabetic rats. These differences remained high when angiotensin
      II-treated control rats [CA] were compared with treated diabetic rats [DA]
      (p<0.005). TSC decreased significantly when diabetic rats were treated with
      insulin. CONCLUSIONS: Diabetes results in oxidative stress, which in turn
      enhances the activity of antioxidant enzymes. This increase in enzyme activity
      inhibits the subcellular remodeling processes, thus also inhibiting concomitant
      cardiac hypertrophy. Insulin treatment decreases the activity of the antioxidant
      system and can enhance the function of other localized tissue-specific growth
      factors. These changes may contribute to the early onset of cardiovascular damage
      detected in diabetic patients.

PMID- 15990682
TI  - Comparative study of keloid formation in humans and laboratory animals.
AB  - BACKGROUND: Keloids are common lesions arising from sites of a previous trauma,
      and are distinguishable from scars by the presence of continuous growth over the
      borders of the original injury. The objective of this article is to improve
      methods for studying keloids using experimental animal models, which may help to
      promote wound-healing research and to attain suitable management of keloids.
      MATERIAL/METHODS: This study consisted of two parts: animal and tissue culture
      experiments. Experimentally induced wounds in animal models were used to
      investigate keloid formation. Tissue cultures of cells in a conditioned medium
      were used to compare the growth rates of fibroblasts obtained from normal skin
      and wounds of experimental animals or from normal human skin and keloids.
      RESULTS: Since keloids are common in humans, hypertrophic scars rather than
      keloids were observed in animal skin wounds. Data from the tissue culture study
      demonstrated an increase in fibroblasts cells in human keloid cultures, but not
      in animal wound cultures. CONCLUSIONS: Studying keloids in experimental animals
      may be more efficient, cheaper, and more practical than to study them in humans.
      Furthermore, the use of tissue culture is a suitable medium in which to study
      keloid cell behavior in order to understand the mechanisms leading to the
      formation of keloids and to attain appropriate, effective management.

PMID- 15990683
TI  - The molecular characterization of clinical isolates from Indian Kala-azar
      patients by MLEE and RAPD-PCR.
AB  - BACKGROUND: Kala-azar is a serious health problem in India. The situation has
      worsened further due to the occurrence of cases unresponsive to antimonials.
      About 30-50% patients do not respond to the prevailing regimen of antimonials.
      The etiological agent for Indian kala-azar has long been known to be Leishmania
      donovani. Recently, in a somewhat startling report, it was claimed that L.
      Tropica causes nearly 25% of current kala-azar cases in India. It was also
      suggested that this might be in some way related to the unresponsiveness to
      pentavalent antimonials in the field. MATERIAL/METHODS: Two independent molecular
      characterization techniques, multilocus enzyme electrophoresis (MLEE) and RAPD
      PCR, were employed to analyze 15 clinical isolates from confirmed Indian kala
      azar patients collected from the eastern part of the country over a period of
      nearly 20 years. The collection included six Sb5+-unresponsive and one PKDL case.
      RESULTS: Our observations strongly suggest that all the clinical isolates,
      including the antimony Sb5+-unresponsive and PKDL ones, we studied were identical
      to the WHO reference strain (DD8) for Leishmania donovani by both the above
      methods and no strain variation might have occurred in two major epidemic and
      inter-epidemic periods. We also observed that none of the Sb5+-unresponsive
      stains we analyzed was related to L. Tropica. CONCLUSIONS: We conclude that L.
      Donovani may be the causal agent for Indian kala-azar and that L. Tropica is most
      likely not an etiological agent for Indian Kala-azar cases that are unresponsive
      to antimonials.

PMID- 15990684
TI  - Curcumin attenuates diet-induced hypercholesterolemia in rats.
AB  - BACKGROUND: Curcumin (a component of turmeric) has long been used as a spice and
      food-coloring agent. In experimental animals, curcumin has shown anti-diabetic,
      anti-inflammatory, cytotoxic and anti-oxidant properties. MATERIAL/METHODS: The
      possible hypolipidemic effect of curcumin was investigated in rats fed a high
      cholesterol diet (HCD). The lipid profile and activities of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) were assessed in serum,
      as well as anti-oxidant parameters in liver tissues. RESULTS: Feeding the animals
      a high cholesterol diet (HCD) for 7 consecutive days (1 ml 100 g(-1)) resulted in
      marked hypercholesterolemia, increased serum level of low-density lipoprotein
      cholesterol (LDL-C), but a decreased serum high-density lipoprotein cholesterol
      (HDL-C). Curcumin admixed with the diet (0.5% w/w) decreased serum total
      cholesterol (TC) by about 21% and LDL-C by 42.5%, but it increased serum HDL by
      50%. The atherogenic indices (LDL-C/HDL-C and TC/HDL-C) were reduced by 52% and
      35%, respectively. Curcumin also decreased the enzyme activities of serum AST and
      ALT, which were increased in HCD animals. CONCLUSIONS: Curcumin showed an obvious
      hypocholesterolemic effect that could be due to an effect on cholesterol
      absorption, degradation or elimination, but not due to an anti-oxidant mechanism.
      This could be supported by the finding in our study that neither HCD nor curcumin
      admixed HCD had any effects on the liver content of glutathione (GSH) or
      superoxide dismutase (SOD) activity. Thus one could argue that ingestion of
      curcumin-containing spices in the diet, especially one rich in fats, could have a
      lipid-lowering effect.

PMID- 15990685
TI  - Three-dimensional models of human 2'-5' oligoadenylate synthetases: a new
      computational method for reconstructing an enzyme assembly.
AB  - BACKGROUND: 2'-5' Oligoadenylate synthetases are interferon-induced enzymes
      important for antiviral cell defense. Tetramer formation of human OAS1 is
      essential for the catalytic activity of the enzyme. However, no structure of any
      oligomeric OAS1 protein has yet been solved and the structural organization of
      the catalytically active tetramers is not known. MATERIAL/METHODS: Using a novel
      conjunction of comparative modeling, molecular surface analysis, and sequence
      analysis, high-resolution models of the known isoforms of human OAS1 were
      prepared. RESULTS: The resulting models suggest different oligomeric states for
      the p40, p46, and p48 isoforms as well as a significant difference in enzymatic
      activity between the p46 and p40/p48 isoforms. CONCLUSIONS: The differences in
      enzymatic activity could result in different susceptibility to viral infection in
      cells expressing individual isoforms. The models are consistent with the
      published biochemical data on human OAS1. The results also suggest that the
      structure of the active OAS2 dimers would be equivalent to that of p40 OAS1
      tetramers.

PMID- 15990686
TI  - Hemochromatosis-causing mutations C282Y and H63D are not risk factors for
      atherothrombotic cerebral infarction.
AB  - BACKGROUND: It has been suggested that iron metabolism may be involved in the
      pathogenesis of atherothrombotic cerebral infarction (ACI). The C282Y and H63D
      mutations in the hemochromatosis (HFE) gene are associated with increased serum
      iron levels and net iron accumulation. The aim of this study was to test the
      hypothesis that the C282Y and H63D mutations in the HFE gene are risk factors for
      ACI in a Slovene population. MATERIAL/METHODS: The C282Y and H63D HFE gene
      mutations were tested in 96 Caucasian patients who had suffered an acute cerebral
      infarction, later confirmed as ACI, and 115 control subjects. Genotypes were
      determined by electrophoresis of the DNA digestion products from RsaI (C282Y) and
      MboI (H63D). RESULTS: We failed to demonstrate that the C282Y and H63D mutations
      were risk factors for ACI in Caucasians. The percentage of C282Y and H63D
      genotypes (dominant model) in ACI-cases (C282Y: 7.3%, n=7; H63D: 28.1%, n=27) did
      not differ significantly (P=0.9 and P=0.7 respectively) from that of the controls
      (C282Y: 7.0%, n=8; H63D: 26.1%, n=30). Logistic regression analysis revealed that
      arterial hypertension, diabetes, and cigarette smoking are independent risk
      factors for ACI, whereas the C282Y and H63D HFE gene mutations are not.
      CONCLUSIONS: We provided evidence that the C282Y and H63D HFE gene mutations were
      not risk factors for ACI in this Slovene population.

PMID- 15990687
TI  - Apoptotic efficacy and inhibitory effect of dexamethasone on matrix
      metalloproteinase.
AB  - BACKGROUND: There is now accumulating evidence that matrix metalloproteinases and
      apoptosis may play an important role in inflammation processes. This study was
      undertaken to determine the effect of dexamethasone on apoptosis and matrix
      metalloproteinase 2 (MMP-2) activity compared with two nonsteroidal anti
      inflammatory drugs (NSAIDs), piroxicam and diclofenac. MATERIAL/METHODS: A
      fibrosarcoma (WEHI-164) cell line was used for evaluating tolerability, MMP-2
      activity, and apoptosis. Dexamethasone, piroxicam, and diclofenac were used at
      concentrations of 10-200 microg/ml in triplicate, two-fold dilutions. MMP-2
      activity was assessed using zymography. For assessment of apoptosis, terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was
      used. RESULTS: Cytotoxicity analysis of dexamethasone showed a greater
      tolerability than diclofenac at concentrations of 10-100 microg/ml, whereas the
      cytotoxic effect of dexamethasone and piroxicam were parallel at doses of 5-80
      microg/ml. The dose-dependent inhibitory effect of dexamethasone on MMP-2
      activity was significantly less than that of the tested NSAIDs at concentrations
      of 10-80 microg/ml, while it increased at doses of >100 microg/ml compared with
      piroxicam. Moreover, the rate of apoptosis for dexamethasone-treated cells was
      20.92%, the values for diclofenac and piroxicam being 78% and 28.15%,
      respectively. CONCLUSIONS: Our findings suggest that dexamethasone is able to
      induce apoptosis and suppress MMP-2 activity. Collectively, dexamethasone might
      be assumed as an agent which could be recommended for chemopreventive purposes.

PMID- 15990688
TI  - Effects of electrical stimulation on skin blood flow in controls and in and
      around stage III and IV wounds in hairy and non hairy skin.
AB  - BACKGROUND: While wounds heal more quickly when electrical stimulation (ES) is
      applied, few studies have examined blood flow (BF) in and around wounds during ES
      in controls with no wounds compared to wounds in diabetic and non diabetic
      subjects. MATERIAL/METHODS: Ten subjects with stage III and IV wounds and 8
      controls were subjected to 5 minutes of biphasic ES (20 milliamps, pulse width
      250 usec). Before, during, and after, BF were measured by a Laser Doppler Imager.
      RESULTS: For the control subjects, in the fingers, BF increased from 307 flux to
      687 after 5 min of ES to one finger but BF also increased to other fingers
      indicating a reflex increase in flow mediated by the sympathetic nervous system.
      For hairy skin, there was a 12% increase in BF with ES and only in the line
      directly between the stimulating electrodes. For the patients (either with or
      without Type 2 diabetes), stimulation in the hand, leg and foot all caused a
      large increase in BF during and for 5 minutes after stimulation. In patients, BF
      was high in the wound area before ES and increased by 53% during, and remained
      high after stimulation was over. CONCLUSIONS: The results show that in wounds,
      where BF is high due to bradykinin and cytokine release, the vasoconstrictor tone
      is not present and electrical stimulation causes a large increase in circulation
      which lasts after stimulation is over.

PMID- 15990689
TI  - Creating a peaceful school learning environment: the impact of an antibullying
      program on educational attainment in elementary schools.
AB  - BACKGROUND: The impact of a bullying and violence prevention program on education
      attainment was studied in five elementary schools (K-5), over a 5-year period.
      MATERIAL/METHODS: A multiple baseline design was used and academic attainment
      test scores of 1,106 students were monitored before and after the introduction of
      the program across the school district. This sample was contrasted with an
      equivalent control sample of 1,100 students from the school district who attended
      schools that did not join the program. RESULTS: Program participation was
      associated with pronounced improvements in the students' achievement test scores.
      Notable reductions in the scores of those students who left schools with active
      programs were also observed. CONCLUSIONS: This simple, low-cost anti-violence
      intervention, involves all those who work in schools, not just students. It
      appears to significantly benefit educational performance of children in the
      participating elementary schools. The program focuses attention on the
      interaction between the bully, victim and audience of bystanders who are seen as
      pivotal in either promoting or ameliorating violence. Buy in to the philosophy by
      teachers & administration is high, because the format allows each school to
      create materials with its own personal stamp, and since there is no classroom
      curriculum add on, the burden to teachers is vastly reduced. Psychiatrists who
      work with schools could easily assist a school to put the program in place as
      part of their consultation work.

PMID- 15990690
TI  - Comorbidity, frailty, and evolution of pressure ulcers in geriatrics.
AB  - BACKGROUND: The prevalence of pressure ulcers (PUs) ranges from 1 to 18% of in
      patients and from 3 to 28% in long-term settings. The aim of our study was to
      verify how comorbidity and frailty influenced the course of PUs in a population
      of elderly subjects hospitalized in a long-term care setting. MATERIAL/METHODS:
      The charts of 125 patients with pressure ulcers were evaluated retrospectively.
      For each subject we took note of PU characteristics (stage, ulcer surface,
      evolution), and clinical characteristics (comorbidity, adverse clinical events,
      and cognitive, functional, and nutritional status). Frailty was defined
      considering age, cognitive functions, and functional and nutritional status.
      RESULTS: In 58 patients (46.4%) there was overall resolution of the lesions,
      while in 39 patients (31.2%) we had "improvement" of PUs. The course of PU was
      not significantly influenced by the patient's physiological characteristics,
      cognitive status, or the initial characteristics of PU. We noticed a significant
      difference in the course of PUs as a function of autonomy level and clinical and
      nutritional status. During the observation period we found significant
      differences in the frailty scores: 87.2% of those who showed an improvement in
      the score had resolution or improvement in PUs, while this occurred in only 27.3%
      of those who had a worsening in the level of frailty. CONCLUSIONS: We maintain
      that integration of multidimensional assessment, with special attention to
      comorbidity status and to frailty (particularly autonomy level and nutritional
      status), and the different approaches may allow optimal healing of PUs.

PMID- 15990691
TI  - Evaluation of two different intermittent pneumatic compression cycle settings in
      the healing of venous ulcers: a randomized trial.
AB  - BACKGROUND: Intermittent pneumatic compression (IPC) has been successfully used
      in the treatment of venous ulcers, although the optimal setting of pressure,
      inflation and deflation times has not yet been established. The aim of this study
      was to compare the effect of two different combinations of IPC pump settings
      (rapid vs slow) in the healing of venous ulcers. MATERIAL/METHODS: 104 patients
      with pure venous ulcers were randomized to receive either rapid IPC or slow IPC
      for one hour daily. The primary and secondary end points were the complete
      healing of the reference ulcer and the change in the area of the ulcer over the
      six months observational period, respectively. RESULTS: Complete healing of the
      reference ulcer occurred in 45 of the 52 patients treated with rapid IPC, and in
      32 of the 52 patients treated with slow IPC. Life table analysis showed that the
      proportion of ulcers healed at six months was 86% in the group treated with the
      fast IPC regimen, compared with 61% in the group treated with slow IPC (p=0.003,
      log-rank test). The mean rate of healing per day in the rapid IPC group was found
      to be significantly faster compared to the slow IPC group (0.09 cm2 vs 0.04 cm2,
      p=0.0002). CONCLUSIONS: Treatment with rapid IPC healed venous ulcers more
      rapidly and in more patients than slow IPC. Both IPC treatments were well
      tolerated and accepted by the patients. These data suggest that the rapid IPC
      used in this study is more effective than slow IPC in venous ulcer healing.

PMID- 15990692
TI  - Relation of airway responsiveness to salbutamol and to methacholine in smokers.
AB  - BACKGROUND: Airway hyperresponsiveness (AHR), the most characteristic feature of
      asthma, is reported in COPD patients and smokers. There are controversies,
      however, regarding airway responsiveness to b-adrenergic agonists in asthma as
      well as COPD and smokers. After our previous studies had shown AHR to b-agonists
      in asthmatic patients, we examined airway responsiveness to salbutamol and its
      relationship to responsiveness to methachline in smokers. MATERIAL/METHODS: The
      threshold concentrations of inhaled salbutamol or methacholine required for a 20%
      change in forced expiratory flow in 1 sec (FEV1), recorded as PC20, or a 35%
      change in specific airway conductance (sGaw), recorded as PC35, was measured in
      14 nonsmoker and 14 smokers. RESULTS: Airway responsiveness to salbutamol was
      greater in smokers (PC20=66.85, PC35=22.74 mg/l) than in nonsmokers (PC20=241.42,
      PC35 =88.72 mg/l, p<0.001 for both). Airway responsiveness to methacholine was
      also significantly greater in smokers (PC20= 1.34 and PC(35)=1.01 g/l) than
      nonsmokers (PC20=5.66 and PC35=4.63 g/l, P<0.001 for both cases). There were
      significant correlations between FEV(1)with both PC20 salbutamol (r=0.577,
      p<0.001) and PC20 methacholine (r=0.638), (p<0.001 for both cases). The
      correlations between airway responsiveness to salbutamol with responsiveness to
      methacholine using both PC(20) (r=0.819) and PC(35) (r=0.783) were also
      statistically significant (p<0.001 for both cases). The slopes of the
      concentration-response curves of both agents were significantly greater in
      smokers than nonsmoker (P<0.001 for all cases). CONCLUSIONS: These results showed
      increased sensitivity of smokers' airways to salbutamol, which correlates closely
      to airway responsiveness to methacholine.

PMID- 15990693
TI  - Possible induction of oral allergy syndrome during specific immunotherapy in
      patients sensitive to tree pollen.
AB  - BACKGROUND: Many studies have shown that specific immunotherapy may prevent the
      development of allergies to new allergens. Recently, however, there have been
      sporadic reports on the possibility of new allergies developing during
      immunotherapy. The aim of this study was to evaluate the possibility of the
      occurrence of food allergy and changes of sIgE concentration in patients
      sensitive to tree pollen during specific immunotherapy. MATERIAL/METHODS: We
      examined 12 patients subjected to desensitization treatment of pollinosis caused
      by allergy to the pollen of Betulaceae trees, in whom only Bet v 1 sIgE was found
      in serum prior to immunotherapy. The control group included 8 allergic patients
      who did not consent to this treatment. RESULTS: Bet v 2 sIgE was detected after 6
      months in 3 patients (25%) and after 18 months in another 2 patients (41.7%
      total). In 2 cases, oral allergy syndrome (OAS) occurred in the course of
      therapy. These findings were accompanied by a concomitant decrease in nasal and
      ocular allergic signs during the birch pollen season in the overwhelming majority
      of patients (91.7%). In the control group, no serum occurrence of Bet v 2 sIgE
      was found during the 18-month observation period. Although no OAS signs appeared
      in any patient, the symptomatic intensity of pollinosis was not reduced.
      CONCLUSIONS: Due to the limitations of currently used vaccines, new allergies may
      be induced during immunotherapy. In sporadic cases these may be accompanied by
      the occurrence of specific clinical manifestations, usually mild.

PMID- 15990694
TI  - Hepatitis C virus associated arthritis in absence of clinical, biochemical and
      histological evidence of liver disease--responding to interferon therapy.
AB  - BACKGROUND: Extrahepatic manifestations associated with Hepatitis C virus (HCV)
      such as arthritis, vasculitis, cryoglobulinemia, are well known. However, HCV
      related arthritis in the absence of clinical, biochemical and histological
      evidence of liver disease is not common. This article deals with such a case and
      its response to interferon therapy. CASE REPORT: We present a case of a 32 year
      old Filipino male who presented with bilateral symmetrical painful swelling of
      multiple joints including, hands, elbows, shoulders, and knees. Serum rheumatoid
      factor, antinuclear antibodies and a comprehensive work-up for rheumatologic
      disorders were all negative. Both initially and subsequently, serological tests
      for hepatitis A, B, and autoimmune liver diseases, Wilson's disease,
      hemochromatosis, syphilis, human immunodeficiency virus (HIV) and
      cryoglobulinemia were negative, initially and subsequently. However, the
      hepatitis C antibody test was positive and hepatitis C viral RNA was detected in
      high titers. The joint symptoms did not improve despite therapy with nonsteroidal
      anti-inflammatory drugs and a short course of prednisone prescribed earlier by
      his primary care physician. The patient then requested and was subsequently
      treated with interferon alpha 2b. RESULTS: The patient responded rapidly to the
      interferon therapy with significant and sustained improvement in joint symptoms
      and disappearance of hepatitis C viral RNA from his serum. CONCLUSIONS: HCV
      arthritis should be considered in the differential diagnosis of seronegative
      arthritis of undetermined etiology even in the setting of normal liver
      chemistries.

PMID- 15990695
TI  - Wolfram syndrome. How much could knowledge challenge the fate? A case report.
AB  - BACKGROUND: Wolfram syndrome (WS) is a rare, autosomic recessive genetic
      disorder. The mortality rate of WS is about 65% before 35 years of age. It
      presents diagnostic challenges in the clinical practice due to its incomplete
      characterization. This report represents the first case of undiagnosed Wolfram
      syndrome in a patient over 53 years old. CASE REPORT: A 53-year-old white woman
      developed a respiratory complication necessitating extended ICU care and
      respiratory rehabilitation. This respiratory complication proved to be a
      consequence of undiagnosed WS. CONCLUSIONS: The report discusses the clinical
      elements that suggested the diagnosis, the problems related to the ICU management
      of this patient, in particular the weaning difficulties, and the need for
      rehabilitation. Finally, the report considers the ethical aspect of timely
      diagnosis on the course and outcome of WS.

PMID- 15990696
TI  - Is restoring regenerative potential a way to prevent anthracycline
      cardiotoxicity? A hypothesis.
AB  - Anthracycline-induced cardiotoxic effects are a serious problem among young
      patients who survive childhood cancer and there is an urgent need to avoid such
      effects. It is generally accepted that the only effective way to do this is to
      prevent cardiac injury during chemotherapy. There are several possible ways to do
      this, though questions remain. Evidence suggests the existence of a resident
      population of self-renewing cardiac stem cells capable of contributing to heart
      repair. Cardiac stem cells have an intrinsically poor regenerative response to
      heart injury. However, recent results point to ways to enhance the formation of
      cardiac precursor cells necessary for regeneration after injury. Moreover, the
      results of a recent study demonstrated that activation of the Notch signaling
      pathway, well characterized for its role in myogenesis and tissue formation
      during embryogenesis, restores impaired regenerative potential of skeletal muscle
      by activating resident precursor cells (satellite cells), which have a markedly
      impaired propensity to proliferate and to produce the myoblasts necessary for
      muscle regeneration. Based on these findings, and because the mechanisms behind
      the cardiotoxic effects of anthracyclines are not fully understood and current
      ways to avoid anthracycline-induced cardiotoxic effects have limitations, we
      hypothesize herein that an attractive way to avoid these effects may be to
      promote repair and regeneration, as opposed to prevent injury (e.g. by
      dexrazoxane).

PMID- 15990697
TI  - The pangenome concept: a unifying view of genetic information.
AB  - A way of viewing the genetic information in all organisms on Earth as
      constituents of the Pangenome is proposed. According to this concept, the
      Pangenome is the common (collective) genetic system of all living organisms, the
      organic molecules and their complexes (DNA- and RNA-containing viruses, plasmids,
      transposons, insertion sequences) involved in the storage and transmission
      processes of genetic information. Pangenomic stability and variability are
      discussed. This concept alerts to the inherent fluidity and transmissibility of
      DNA among organisms of all types, including horizontal gene transfer between
      closely related and formally unrelated macro- and microorganisms. The roles of
      death and of all known food chains as universal ways of gene distribution among
      different organisms are discussed. The contribution of bacteria and viruses in
      maintaining the circulation of genes within the Pangenome is presented. This
      concept implies that newly emerging genes are not bound to disappear together
      with the death of an organism or the extinction of a species and microorganisms
      are the main pool of genes. Some negative aspects of the intervention of
      molecular genetics, biotechnology, and ecology, including the spread of
      transgenic plants and animals, are summarized. It is shown that this concept may
      be used in medicine for the prognosis of an epidemic situation, particularly
      newly spreading pathogens, and for the development of new methods for the
      prophylaxis and early diagnosis of oncologic diseases. This concept can also help
      to find promising approaches to the discovery of drugs with novel principles of
      action.

PMID- 15990698
TI  - Systemic effects of cancer: role of multiple proteases and their toxic peptide
      products.
AB  - Cachexia, or the loss of skeletal muscle, adipose tissue and immunological
      competence, is a common systemic condition in advanced cases of cancer, and is a
      frequent cause of death. There have been many reports that small peptides
      isolated from tumors induce systemic effects correlated with cachexia upon
      injection into mice or addition to cell cultures. Only recently has evidence been
      presented for the origin of these peptides from the large increase in proteolytic
      enzymes found in tumors. Additional evidence is presented here for a major role
      of tumor peptides in producing effects associated with cachexia. Such peptides of
      low molecular weight were found to produce lipolysis in adipose tissue.
      Fibrinogen degradation products from the plasma of cancer patients and other
      chronic diseases suppress activation of the immune response. Some proteases of
      the cathepsin class occur in high concentration at the surface of transformed
      cells where the pH is low enough to allow digestion of pericellular proteins;
      other cathepsins elevated in tumors are highly active at physiological pH.
      Cathepsin L is the major excreted protein of cultured cells transformed by
      viruses or chemicals and is likely to form toxic peptides by digestion of
      extracellular proteins. Even normal liver and skeletal muscle of some cancer
      patients and tumor-bearing animals exhibit significant increases in cathepsins
      and components of the ubiquitin-proteasesome pathway which would add to
      circulating peptides. These observations argue for a central role of multiple
      proteases and their proteolytic products in producing the debilitating systemic
      effects of cancer.

PMID- 15990699
TI  - Circulating transforming growth factor beta-1: a partial molecular explanation
      for associations between hypertension, diabetes, obesity, smoking and human
      disease involving fibrosis.
AB  - Transforming growth factor beta-1 is involved in local signaling for a variety of
      human diseases including renal diseases, cardiac hypertrophy and fibrosis in
      heart failure, hepatic fibrosis, and pulmonary fibrosis. Elevated levels of
      circulating transforming growth factor beta-1 result in organ fibrosis in animal
      models. In humans smoking, hypertension, diabetes and obesity appear to result in
      elevated circulating levels. This paper outlines a hypothesis that elevated
      circulating levels of transforming growth factor beta-1 are part of the molecular
      link between several entities that have epidemiologic ties including
      hypertension, diabetes, smoking and obesity on one hand and diseases resulting in
      organ fibrosis on the other including renal disease and cardiac fibrosis and
      hypertrophy in heart failure. Additionally, it is suggested that elevated levels
      are not simply a marker of a similar mechanism of disease production but that
      elevated levels of circulating transforming growth factor beta-1 lead to disease
      production and to the synergy of risk factors seen in production of human
      fibrotic diseases.

PMID- 15990700
TI  - COX-2 inhibitors and metabolism of essential fatty acids.
AB  - Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke
      that is attributed to their ability to inhibit prostacyclin (PGI2), lipoxins,
      resolvins, and endothelial nitric oxide (eNO) but not platelet COX-1 derived
      thromboxane A2 (TXA2). In contrast, aspirin blocks both COX-1 and COX-2 enzymes
      that, in turn, increases intracellular concentrations of dihomo-gamma-linolenic
      acid (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) and reduced formation of eicosanoids. On the other
      hand, such an increase is much less with specific COX-2 inhibitors since they do
      not block the formation of eicosanoids through COX-1 pathway. DGLA, AA and EPA
      form precursors to PGE1, PGI2, and PGI3 respectively, which are potent
      vasodilators and platelet anti-aggregators, and thus aid in the prevention of
      thrombus formation. EPA has anti-arrhythmic action, and EPA, DHA (docosahexaenoic
      acid), DGLA, and PGE1 have anti-inflammatory actions as well. EPA, DHA, and AA
      augment eNO formation that has anti-atherosclerotic action. Hence, combining EFAs
      with COX-2 inhibitors will prevent thrombotic cardiovascular events.

PMID- 15990701
TI  - Mitochondrial encephalomyopathies: advances in understanding.
AB  - Mitochondrial encephalomyopathies encompass a group of disorders that have
      impaired oxidative metabolism in skeletal muscles and central nervous system. As
      the field of mitochondrial medicine takes shape and physicians in all specialties
      become increasingly aware of respiratory chain or oxidative phosphorylation
      (OXPHOS) related disorders, their prevalence remains largely unknown. The unique
      features of the mitochondrial genome and the dual control over this important
      cellular apparatus makes the clinical presentation variable and diagnosis
      difficult. There is a confounding variation in phenotype and genotype, and the
      natural history of the disorders in individual patients is not accurately
      predictable. Only recently have things begun to fall into place and some
      phenotypes defined. Diagnosis requires a complex battery of clinical studies
      coupled with diagnostic findings on muscle biopsy (abnormal structure,
      histochemistry, or enzyme studies) or DNA testing. However, a reasonably
      confident diagnosis can be made by viewing the clinical presentation in the light
      of family history and some basic, routinely available laboratory investigations.
      This review tries to give a brief account of mitochondrial structure, function
      and genetics, and clinical presentation, evaluation, and treatment in suspected
      cases of mitochondrial encephalomyopathies.

PMID- 15990702
TI  - Adult neurogenesis in the mammalian central nervous system: functionality and
      potential clinical interest.
AB  - In the past decades, much evidence has confirmed that neurogenesis occurs in the
      adult brain and that neural stem cells reside in the adult central nervous
      system, overturning the long-held dogma that we are born with a certain number of
      nerve cells and that the brain cannot generate new neurons and renew itself. In
      the adult brain, neurogenesis occurs mainly in two areas: the hippocampus and the
      subventricular zone, and self-renewing, multipotent neural stem cells have been
      isolated and characterized in vitro from various regions of the adult central
      nervous system. Though significant advances have been made in this field of
      research, the identification and function of neural stem cells in the adult
      central nervous system remain the source of debate and controversy. Neurogenesis
      is modulated by several normal and pathologic conditions, suggesting the
      involvement of the hippocampus and the subventricular zone in a broad range of
      functions, and that environmental stimuli and pathological conditions may have
      long-term consequences on the architecture and functioning of the central nervous
      system. Neurogenesis is involved in processes such as learning, memory, and
      depression, and may also be involved in regenerative attempts after injuries to
      the central nervous system. However, the contribution of neurogenesis to these
      phenomena remains to be elucidated. Neural stem cells also hold the promise to
      cure a broad range of neurological diseases and injuries. Cell therapeutic
      interventions may involve both cell transplantation and the stimulation of
      endogenous neural progenitor cells.

PMID- 15990703
TI  - Etiology and pathogenesis of inflammatory bowel disease.
AB  - Despite of scientific efforts during the last decades, etiology and pathogenesis
      of the two major inflammatory bowel diseases, namely Crohn's disease and
      ulcerative colitis, remain rather unclear. According to the results of multiple
      studies it is accepted that the development of either disease is the result of an
      exaggerated or insufficiently suppressed immune response to a hitherto undefined
      luminal antigen, probably derived from the microbial flora. This inflammatory
      process leads to the well-known mucosal damage and therefore a further
      disturbance of the epithelial barrier function, resulting in an increased influx
      of bacteria into the intestinal wall, even further accelerating the inflammatory
      process. However, these immunological disturbances that have been investigated
      extensively during the past years have to be considered on the genetic background
      of the individual patient and the environmental factors the patient is exposed
      to. In this review we will attempt to summarize the current knowledge about risk
      factors for inflammatory bowel diseases, genetic and environmental factors of IBD
      and focus on the immunological alterations of innate and acquired immune system
      underlying Crohn's disease and ulcerative colitis.

PMID- 15990704
TI  - Extraintestinal manifestations of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) predominantly affects the gastrointestinal
      system but it is associated with a large number of extraintestinal manifestations
      (EIM). These extraintestinal disorders can significantly contribute to morbidity
      and impair the overall life quality. EIM may be diagnosed before, concurrently
      with, or after the diagnosis of IBD is made. The precise etiology of EIM remains
      unknown. It currently is believed that mucosa from the underlying bowel disease
      may provide associated immune responses for the inflammatory process in the
      extraintestinal sites. The involvement of autoimmune mechanisms has been
      suggested when the shared and unique epitopes in the human colon, eye, joint and
      biliary epithelium were detected. Recently, the presence of long-lived
      populations of memory lymphocytes has been discovered which arise as a
      consequence of bowel inflammation and express homing receptors that direct their
      migration not only to the gut but also to the extraintestinal sites. The most
      common extraintestinal disorders associated with IBD include dermatologic,
      ophthalmologic, musculoskeletal and hepatobiliary diseases, although virtually
      every organ system may be involved. If these disorders can be considered as the
      real extraintestinal manifestations of IBD or represent just association between
      different syndromes of autoimmune etiology, is still not clear. It is important
      to acquire knowledge on these extraintestinal manifestations of Crohn's disease
      and ulcerative colitis to start the respective treatment early.

PMID- 15990705
TI  - Frequency of bcl-2/IgH translocation in patients with non-Hodgkin's lymphoma and
      chronic hepatitis C virus infection.
AB  - AIM: It has been previously suggested that t(14;18) translocation of bcl-2 to the
      immuno-globulin heavy chain (IgH) locus may contribute to pathogenesis of
      lymphoproliferative disorders related to hepatitis C virus (HCV) infection,
      including type II mixed cryoglobulinemia (MC). METHODS: In this study, the
      presence or absence of t(14;18) translocation was determined in tumor biopsy
      specimens and peripheral blood mononuclear cells (PBMCs) for 48 NHL patients with
      chronic HCV infection. RESULTS: In tumor biopsy specimens from 32 HCV-positive
      NHL patients, bcl-2/IgH translocation was detected in 1 of 13 patients with MC
      syndrome (7.7%) and 3 of 19 patients without MC syndrome (15.8%). In PBMCs from
      23 HCV-positive NHL patients, this translocation was observed in 3 of 6 patients
      with MC syndrome (50%) and 4 of 17 patients without MC syndrome (23.5%).
      Interestingly, bcl-2/IgH translocation was found in 2 extranodal marginal zone B
      cell lymphoma tissues from HCV-infected patients. CONCLUSIONS: However,
      additional studies are required to better clarify the relationship between this
      translocation and extranodal marginal zone B-cell lymphoma development. Although
      the frequency of bcl-2/IgH translocation in PBMCs from patients with chronic HCV
      infection is higher than that of other NHL patients, this increased translocation
      rate remains to be elucidated.

PMID- 15990706
TI  - Radio-frequency thermal ablation (RFTA) of small hepatocellular carcinoma in
      patients with cirrhosis. Experience at a single tertiary referral center.
AB  - AIM: Radio-frequency thermal ablation (RFTA) may prolong the survival of patients
      with small hepatocellular carcinoma (HCC) associated with cirrhosis. The aim of
      this study was to evaluate efficacy and safety of RFTA. METHODS: We performed the
      Kaplan-Meier analysis to estimate the survival rate in 69 consecutive patients
      with HCC (mean age 66+/-6.5 years; 44/25 male/female; 56 Child-Pugh class A and
      13 Child-Pugh class B) treated by RFTA. A single lesion was observed in 60/69
      (87%), two lesions in 8/69 (11.6 %), and 3 lesions in 1/69 (1.4 %) of patients.
      The tumor size was = or <3 cm in 60/69 (87%). RESULTS: Twenty-two patients died
      during follow-up. Overall survival rates were 81%, 66%, and 46% at 1-, 2-, and 3
      years, respectively. Cancer-free survival rates were 64% at 1 year, 30% at 2
      years and 25% at 3 years. The 3-years rate of appearance of separate new lesions
      and local recurrence were 27.5% (19/69) and 26 % (18/69). CONCLUSIONS: Our study
      shows that patients with HCC and compensated cirrhosis may benefit from RFTA
      treatment, especially for tumors = or <3 cm. Nevertheless, the high rate of
      recurrence (both local and distant) points out the palliative role of this
      therapy.

PMID- 15990707
TI  - Time-course of diastolic dysfunction in different stages of chronic HCV related
      liver diseases.
AB  - AIM: A hyperdynamic circulatory pattern in advanced liver disease is known since
      a long time. The first studies evaluating cardiac function in cirrhosis were
      performed in patients with alcoholic liver disease and thus this condition was
      attributed to the toxic effects of ethanol. A reduced performance of the left
      ventricle after physical and pharmacological strains along with an altered
      diastolic function has been demonstrated also in postviral cirrhosis. Many
      factors are involved in advanced cirrhosis whereas little is known in the earlier
      stages of disease. METHODS: To this aim we have investigated patients with
      different stages of hepatitis C virus (HCV)-related liver disease to detect the
      time-course of diastolic dysfunction. An impaired relaxation and increased
      thickness of left ventricular walls along with an altered pattern of transmitral
      flow can be easily detected by means of echocardiography. RESULTS: In chronic
      hepatitis diastolic function is preserved but increased thickness of left
      ventricle parietal walls can be detected in patients with fibrosis on liver
      biopsy. The typical pattern of diastolic dysfunction is observed in Child A
      cirrhotic patients and in Child C ascitic patients but thickness of parietal
      walls is more relevant in the former group. Chronic aldosterone blockade could
      exert favourable effects in heart remodeling suggesting a potential role of these
      drugs in cirrhotic cardiomyopathy. CONCLUSIONS: The presence of increased
      thickness of left ventricle parietal walls in chronic hepatitis C in the
      precirrhotic stage point to a putative role of HCV in this heart structural
      abnormality that can become a co-factor in the more advanced stages of cirrhosis
      when portal hypertension and its deleterious effects on systemic hemodynamics,
      cardiac function and structure become manifest.

PMID- 15990708
TI  - Chronic anaemia and adhesion molecules in patients with liver cirrhosis. A
      preliminary report.
AB  - AIM: The aim of our study was to investigate circulating levels of intercellular
      adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1)
      in cirrhotic patients, with and without chronic anaemia, to establish whether
      there was a relationship between inflammatory activity and anaemia. METHODS: We
      investigated 14 anaemic (mean hemoglobin value 10.65+/-1.06 g/dL) and 14 non
      anaemic (mean hemoglobin value 13.8+/-0.89 g/dL) subjects affected by virus C
      related liver cirrhosis comparable for sex, age and degree of liver dysfunction
      such as expressed by Child-Pugh classification. Circulating sICAM-1 and sVCAM-1
      were measured by EIA commercial kit (R&D System Co, Abington, UK) and mean+/-
      standard deviation values in two groups were compared by t-test and Kruskall
      Wallis test. RESULTS: Mean+/-standard deviation sICAM-1 was 35.06+/-4.06 ng/mL in
      anaemic and 23.39+/- 6.1 ng/mL in non anaemic cirrhotic patients. Mean+/-standard
      deviation sVCAM-1 was 47.66+/-8.18 ng/mL in anaemic 31.77+/-6.08 ng/mL in non
      anaemic patients, respectively. Statistical analysis showed a significant
      difference between the two groups both in sICAM-1 (p=0.01) and sVCAM-1 (p=0.03)
      values. CONCLUSIONS: Our study show that chronic anaemia, in liver cirrhosis, is
      associated to a greater increase of circulating adhesion molecules and suggests
      that inflammation may contribute to persistence of anaemic state, worsening the
      outcome of cirrhotic patients.

PMID- 15990709
TI  - [Effects of a new pharmacological complex (silybin + vitamin-E + phospholipids)
      on some markers of the metabolic syndrome and of liver fibrosis in patients with
      hepatic steatosis. Preliminary study].
AB  - AIM: This open preliminary pilot study was aimed to evaluate the effect of a new
      pharmaceutical complex (silybin+vitamin E+phospholipids - RealSIL-IBI-Lorenzini
      Pharmaceutical, Italy) on some parameters of metabolic syndrome and of liver
      fibrosis in patients with non alcoholic fatty liver disease (NAFLD) with or
      without the contemporaneous presence of hepatitis C virus (HCV)-related chronic
      hepatitis. METHODS: Eighty five patients were consecutively enrolled in the study
      and divided in 2 groups; the first group was represented by 59 patients affected
      by NAFLD, negative for other known causes of chronic liver damage (M/F= 39/20;
      median age and range: 44 years, 22-76, group A); the second group was represented
      by 26 patients (M/F=19/7; median age and range 51 years, 20-75, group B) with HCV
      related chronic hepatitis associated to NAFLD. Adverse events and drop-outs were
      absent in all group and compliance at the study was absolute. RESULTS: This open
      preliminary study shows that the new compound silybin+vitamin E+ phospholipids is
      active, in vivo, and produces some therapeutic effects in patients with different
      forms of chronic liver damage. In particular, it improves insulin resistance and
      plasma levels of markers of liver fibrosis in patients in whom these parameters
      are particularly altered. CONCLUSIONS: Our data have a role of suggestion to
      further evaluate, through a controlled trial, a possible therapeutic use of this
      new compound in the management of patients with NAFLD.

PMID- 15990710
TI  - Immunological markers anti-saccharomyces cerevisiae antibodies (ASCA) and anti
      neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: a helpful
      diagnostic tool.
AB  - AIM: Nowadays the diagnosis of inflammatory bowel disease (IBD) and the
      differentiation between Crohn disease (CD) and ulcerative colitis (UC) is still
      based on morphological changes identified at endoscopy, radiology, and
      histopathology. In 5-15% of cases this differentiation is not possible (diagnosed
      with indeterminate colitis). METHODS: We evaluated if recently developed
      commercial kits for the determination of anti-Saccharomyces Cerevisiae antibodies
      (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) are useful in
      differentiating cases of UC from CD diseases with a consequent reduced number of
      undefined colitis and improved clinical management. Sera from 56 consecutive
      patients with a clinical diagnoses of IBD were evaluated in a blinded fashion for
      the presence of ASCA IgA and IgG and ANCA IgG with 2 different diagnostic
      methods: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay
      (ELISA). RESULTS: In our cases we observed good agreement between
      histopathological examination and laboratory results and the combined use of ASCA
      and ANCA yielded a correct diagnosis in 93% of patients with CD and in 97% of the
      UC patients. CONCLUSIONS: We confirm the value of the test for the diagnosis of
      CD and UC and the differentiation from other forms of colitis.

PMID- 15990711
TI  - Biliopancreatic diversion. Clinical experience.
AB  - AIM: Biliopancreatic diversion (BPD) has been accepted as an effective surgical
      treatment of morbid obesity. The paper presents the results of a personal
      clinical experience with this procedure, with special focus on the quality of
      life. METHODS: From January 1, 1992 to June 30, 2002, 122 patients (F/M: 108/14,
      mean age: 40.2 years, range 21-61) underwent BPD. Mean preoperative body weight
      was 122.4 kg (range 91-200), with a mean Body Mass Index of 49.1 kg/m2 (range 38
      78). Three of these patients were converted from a previous vertical banded
      gastroplasty to BPD (1 patients with stomach preservation). After at least a 36
      month follow-up, 10 patients underwent abdominal dermolipectomy (8 associated to
      incisional hernia repair, 1 associated to thigh dermolipectomy). RESULTS: Mean
      postoperative hospital stay was 12 days (range: 11-30). Follow-up is currently in
      progress in all patients. Weight loss of initial overweight was 75% in 88
      patients with a 36-month follow-up, with excellent long-term weight maintenance.
      Protein deficiency was the main specific complication, encountered in 6 patients
      (4.9%). Beneficial effects, other than those consequent to weight loss, included
      permanent normalization of serum cholesterol and glucose without any medication
      and on a totally free diet. Almost 80% of the patients reported an improvement in
      their self-esteem, physical activity, work condition and social life.
      CONCLUSIONS: This clinical experience supports the effectiveness and safety of
      BPD, despite some criticism. The small number of side effects and complications,
      the excellent weight loss and the recovery of most co-morbidity leads to a great
      improvement in quality of life.

PMID- 15990712
TI  - Combined endovascular and microsurgical approach in the treatment of giant
      paraclinoid and vertebrobasilar aneurysms.
AB  - AIM: The aim of this study is to present the application of endovascular
      intraoperative occlusion of the parent artery during the microsurgical treatment
      of giant paraclinoidal internal carotid artery aneurysms (ICA) and of complex
      vertebrobasilar junction aneurysms . METHODS: Five cases of giant paraclinoidal
      ICA aneury-sms were treated by direct surgical approach. In the operatory room
      any patient underwent angiography and balloon occlusion test using a mobile
      digital subtraction angiograph. Thereafter the catheter was left in the aortic
      arch. Through an extended pterional craniotomy, it was possible to evidentiate
      the aneurismal sac. The proximal control of the vessel was achieved inflating a
      double-lumen balloon; clipping of the aneurysm was achieved, because of pressure
      lowering inside the aneurysm. Also a giant vertebrobasilar junction aneurysm was
      treated by this combined technique: using a posterolateral approach the control
      of the omolateral vertebral artery was obtained by temporary clipping above
      PICA's origin; the control of controlateral artery was obtained inflating a
      balloon introduced through the femoral artery. These combined manoeuvres
      determined sac deflation, allowing an easier clipping. RESULTS: Aneurysm
      obliteration was achieved with preservation of the circulation without
      complications in all cases. CONCLUSIONS: The endovascular procedure allows safer
      and reliable proximal control of paraclinoidal ICA and vertebral artery during
      the microsurgical treatment of paraclinoid and vertebrobasilar junction
      aneurysms.

PMID- 15990713
TI  - Spinal meningiomas: evaluation of 41 patients.
AB  - AIM: Spinal meningiomas are relatively frequent intraspinal tumors. They
      constitute 25-46% of all primary spinal neoplasms. METHODS: Forty-one patients
      with spinal meningiomas surgically treated between 1986 and 2001 are reviewed in
      this report. There were 32 females and 9 males, aged 16 to 73 years old. Tumor
      location was cervical in 7 cases and thoracic in 34 cases. All tumors were
      intradural. All of the patients were operated by laminectomy in prone position.
      RESULTS: Total excision was achieved in 40 (98%) patients and subtotal excision
      in 1(2%). The majority of the tumors were meningothelial (42%) or psammomatous
      (25%). There was no surgical mortality. Four patients (10%) suffered from
      morbidity: One patient with CSF fistula, 1 deep venous thrombosis, 1 case with
      paraparesis and 1 wound infection was seen. Neither multiple meningiomas nor
      malign meningiomas were seen in our series. CONCLUSIONS: Spinal meningiomas are
      benign tumors and should be excised totally. If the preoperative neurological
      status is not complicated, fairly good outcome can be achieved.

PMID- 15990714
TI  - Supratentorial cavernomas in eloquent brain areas: application of neuronavigation
      and functional MRI in operative planning.
AB  - AIM: Cavernomas located in eloquent areas of cerebral hemispheres represent a
      challenge for the neurosurgeon. An accurate surgical approach is essential to
      completely remove the lesion with function preservation. Aim of this study was to
      evaluate the usefulness of integration between standard magnetic resonance
      imaging (MRI) for neuronavigation and functional MRI (fMRI) in preoperative
      planning and intraoperative removal of cavernomas. METHODS: Between June 2000 and
      December 2002, 21 patients underwent surgery for supratentorial subcortical
      cavernomas. Eleven lesions were located adjacent to eloquent brain areas. All the
      patients in the series underwent MRI for neuronavigation and, since January 2002,
      in 6 cases of lesions located in eloquent areas, fMRI was also performed, with
      subsequent images fusion. The surgical approach was performed via the transgyral
      route under conventional and ultrasound-guided neuronavigation. RESULTS: All the
      lesions were totally removed. No morbidity was seen in patients harbouring
      lesions in non eloquent areas. Four patients with lesions in critical areas
      suffered transient focal deficits, but only one patient of this series was
      operated on by the auxilium of image fusion. In 7 patients operated on by
      conventional image-guided surgery and affected by preoperative seizures, no
      further seizures were observed after surgery. In 3 patients more hosting lesions
      neighbouring critical areas, the perilesional ring was not removed, observing
      persistence of seizures pharmacologically treated. In 4 of the 6 patients (all
      affected by seizures), operated on by fMRI auxilium, lesion removal was
      associated to the removal of the perilesional ring. No further epilepsy was seen
      in these patients. CONCLUSIONS: In all the cases the use of neuronavigation
      allowed minimally invasive approaches and radical excision of the lesions.
      Moreover, fMRI seemed to provide important additional information in patients
      with lesions in eloquent brain areas, allowing a more aggressive approach on the
      perilesional tissue to the aim of resolving seizures, in absence of an increase
      in the morbidity rate.

PMID- 15990715
TI  - Spontaneous intramedullary hematoma. A case report.
AB  - The authors describe a case of sudden onset of numbness and weakness of both
      lower limbs along with bladder involvement, magnetic resonance imaging (MRI) of
      the dorsolumbar spine revealed an intramedullary mass. Surgery revealed it to be
      an intramedullary hematoma. The relevant literature is reviewed.

PMID- 15990716
TI  - Ectopic pituitary adenoma located at the pituitary stalk. Case report.
AB  - Suprasellar located ectopic pituitary adenomas are unusual tumors. We report a
      rare case of suprasellar prolactinoma arising from the pars tuberalis in a 37
      year-old woman. Menstrual disregulation and bitemporal hemianopsia were the main
      complaints. Blood tests revealed hyperprolactinemia. In magnetic resonance the
      tumor was totally supradiaphragmatic. Pterional craniotomy and total tumor
      excision was performed. The pituitary stalk was preserved. Histopathologic
      diagnosis was a pituitary adenoma immunoreactive for prolactin. Pituitary
      hormonal functions returned to normal at 6 months postoperatively. No
      complications were seen in the postoperative period. An ectopic adenoma should be
      suspected in a patient with suprasellar tumor and hyperprolactinemia. Surgical
      excision of this tumor may result with normal pituitary functions and normal
      visual acuity.

PMID- 15990717
TI  - From the descriptive towards inferential statistics: hundred years since
      conception of the Student's t-distribution.

PMID- 15990718
TI  - Love and stress.

PMID- 15990719
TI  - The Neurobiology of Love.
AB  - Love is a complex neurobiological phenomenon, relying on trust, belief, pleasure
      and reward activities within the brain, i.e., limbic processes. These processes
      critically involve oxytocin, vasopressin, dopamine, and serotonergic signaling.
      Moreover, endorphin and endogenous morphinergic mechanisms, coupled to nitric
      oxide autoregulatory pathways, play a role. Naturally rewarding or pleasurable
      activities are necessary for survival and appetitive motivation, usually
      governing beneficial biological behaviors like eating, sex, and reproduction.
      Yet, a broad basis of common signaling and beneficial neurobiological features
      exists with connection to the love concept, thereby combining physiological
      aspects related to maternal, romantic or sexual love and attachment with other
      healthy activities or neurobiological states. Medical practice can make use of
      this concept, i.e., mind/body or integrative medicine. Thus, love, pleasure, and
      lust have a stress-reducing and health-promoting potential, since they carry the
      ability to heal or facilitate beneficial motivation and behavior. In addition,
      love and pleasure ensure the survival of individuals and their species. After
      all, love is a joyful and useful activity that encompasses wellness and feelings
      of well-being.

PMID- 15990720
TI  - Adrenal cortex -- the next biological clock?
AB  - It is well known that plasma levels of dehydroepiandrosterone (DHEA), a steroid
      hormone secreted by zona reticularis (ZR) of the adrenal cortex, reach the
      maximal values in the third decade of life and then gradually decline with age.
      Moreover, the DHEA deficiency is probably responsible for several functional
      disturbances connected with aging. It was also found that ZR reaches its
      definitive volume at puberty and undergoes selective atrophy during the aging.
      Thus, the decline of DHEA may be a simple consequence of ZR atrophy in aged
      subjects. A hypothesis presented here attempts to explain the mechanism of the
      age-related ZR atrophy and is based on the adrenal cortex cell kinetics. In the
      adrenal cortex the cell proliferation indices are lower when we pass from zona
      glomerulosa (ZG) to the inner zones and are the lowest in ZR. In contrast, the
      apoptotic index is the highest in ZR. It is suggested that adrenocortical cells
      renew from the progenitor cells located in ZG /zona fasculata boundary and /or in
      subcapsular layer. These cells migrate centripetally undergoing the subsequent
      steps of differention and consecutive divisions - and - if not die en route -
      reach the most central localization in ZR. In consequence, ZR includes the
      "oldest" adrenocortical cells which probably in majority reached the "Hayflick's
      number" and cannot divide. This results in the preponderance of apoptosis over
      proliferation leading to progressive ZR atrophy followed by a decline of
      secretion of ZR-derived steroid hormones.

PMID- 15990721
TI  - Caloric restriction reduces cell loss and maintains estrogen receptor-alpha
      immunoreactivity in the pre-optic hypothalamus of female B6D2F1 mice.
AB  - Life-long calorie restriction (CR) remains the most robust and reliable means of
      extending life span in mammals. Among the several theories to explain CR actions,
      one variant of the neuroendocrine theories of aging postulates that changing
      hypothalamic sensitivity to endocrine feedback is the clock that times phenotypic
      change over the life span. If the feedback sensitivity hypothesis is correct, CR
      animals should display a significantly different pattern of hormone-sensitive
      cell density and distribution in the hypothalamus. Of the many endocrine signal
      receptors that may be involved in maintaining hypothalamic feedback sensitivity,
      our study has selected to begin mapping those for estrogen (E). Altered
      hypothalamic sensitivity to E is known to schedule reproductive maturation and
      influence reproductive senescence. Taking estrogen receptor-alpha (ERalpha)
      immunoreactivity as an index of sensitivity to E, we counted ERalpha
      immunoreactive and non-immunoreactive cells in the pre-optic hypothalamus of
      young (6 weeks), ad-libitum (Old-AL) fed old (22 months), and calorie restricted
      (Old-CR) old (22 months) female B6D2F1 mice. An automated imaging microscopy
      system (AIMS) was used to generate cell counts for each sampled section of pre
      optic hypothalamus. Results show a 38% reduction in ERalpha immunoreactive cells
      and an 18% reduction in total cell numbers in AL-old mice in comparison to young
      mice. However, CR mice only show a 19% reduction in ERalpha immunoreactive cells
      and a 13% reduction in total cell numbers in comparison to young mice. This
      indicates CR prevents age-related cell loss and maintains estrogen sensitivity in
      the pre-optic hypothalamus of old female B6D2F1 mice.

PMID- 15990722
TI  - The atypical antipsychotics quetiapine, risperidone and ziprasidone do not
      increase insulin release in vitro.
AB  - OBJECTIVE: In the light of the recent finding that the atypical antipsychotics
      clozapine and olanzapine have a stimulatory effect on basal insulin release in
      vitro, the influence on insulin release of three other atypical agents;
      quetiapine, risperidone and ziprasidone, was examined. METHODS: The effect of
      each atypical antipsychotic in a concentration of 10(-6) M was investigated on
      both basal and glucose-stimulated insulin release from isolated rat pancreatic
      islets. RESULTS: No difference in effect on insulin release was found for any of
      the three atypical antipsychotic substances compared to controls without
      antipsychotics, either in basal or in glucose-stimulated insulin release.
      CONCLUSION: This study demonstrates that the main compounds of quetiapine,
      risperidone and ziprasidone do not increase insulin release from isolated
      pancreatic islets, which stands in clear contrast to what has been found
      previously for clozapine and olanzapine. Thus, atypical antipsychotics seem to
      differ in their effect on insulin release in vitro.

PMID- 15990723
TI  - Survivin expression in pituitary adenomas.
AB  - Survivin has received great attention due to its expression in many human tumours
      and its potential as a therapeutic target in cancer. Its expression is
      developmentally regulated: present during fetal development, it is undetectable
      in terminally differentiated normal adult tissue. Survivin expression has been
      described to be cell cycle-dependent and restricted to the G2-M checkpoint, where
      it inhibits apoptosis in proliferating cells. OBJECTIVES: The aim of our study
      was to determine the survivin expression in different types of pituitary
      adenomas. METHODS: Tissue samples were obtained during surgical removal of the
      tumour from 12 patients with diagnosed: acromegaly in seven cases, non
      functioning pituitary tumours in four cases and prolactinoma in one case. Six
      patients with acromegaly received long-acting somatostatin analogues before
      tumour resection. After RNA extraction and cDNA synthesis, the amplification of
      specific survivin's gene fragment was performed. RESULTS: In agreement with the
      current view that survivin is a tumor-associated antigen, highly expressed in
      various tumours, we found the presence of survivin expression as a characteristic
      feature of human pituitary adenomas. The findings of our study demonstrated the
      presence of an active survivin gene in all twelve analysed pituitary tumours.
      CONCLUSIONS: Based on these findings, we conclude that the estimation of survivin
      expression in human pituitary tumours may help predict tumour growth and
      prognosis.

PMID- 15990724
TI  - First cases in the Czech Republic of the Hallervorden-Spatz disease resulting
      from mutation in the pantothenate kinase 2 gene.
AB  - Hallervorden-Spatz disease (HSD) was and is known as a rare disorder primarily
      characterized by progressive extrapyramidal dysfunction and dementia alongside
      optic nerve atrophy or retinal degeneration and pyramidal signs. The rate of
      occurence of HSD is thus far unknown. Progress in DNA diagnostics stirred up a
      nomenclature and from HSD, or, perhaps better put, the Hallervorden-Spatz
      syndrome, crystallized the pantothenate kinase-associated neurodegeneration
      (PKAN) as a clearly defined entity on the level of DNA. In this paper, we present
      our first results and experience in the diagnosis of PKAN in the Czech Republic
      and discuss questions related to differential diagnosis.

PMID- 15990725
TI  - The quest of cavum septi pellucidi: obscure chance event discovery or the result
      of some encoded disturbance? Developmental cerebral dysplasias, cavum septi
      pellucidi and epilepsy: clinical, MRI and electrophysiological study.
AB  - OBJECTIVES: Developmental cerebral dysplasias are frequent causes of epilepsy.
      The early stage of gestation, mainly the period of neural crest separation and
      neuroblast migration (disturbance of midline structures, heterotopias, cortical
      dysplasias and disturbance of the ventricular and vascular formation), may be
      considered as a cause of serious cerebral dysplasia. The aim of the study was
      focused on frequent simultaneous occurrences of epileptic seizures and the defect
      or abnormality of the ventricular system - cavum septi pellucidi (CSP). MATERIAL
      AND METHOD: In our study the clinical symptoms, EEG and somatosensory evoked
      potentials (SEP's) following median nerve stimulation and MRI pictures in the
      group of patients with CSP (n= 35), were analyzed. In the SEP analysis, a control
      group of normal, healthy volunteers (n = 40) and a group of age matched patients
      with epileptic seizures of different origin, without structural lesions evident
      on MRI (n=21), were used. RESULTS: Analysis of the patient population with CSP
      (CSP was confirmed by MRI) showed that approximately in 2/3 cases, different
      types of cranio-cerebral dysplasias were evident on MRI. More than 2/3 of the
      patients with CSP showed epilepsy and an abnormal EEG record, however, focal EEG
      changes were seen more frequently in the group of patients with epilepsy without
      CSP, than in patients with CSP. The SEP's in patients with CSP showed a
      statistically significant prolongation of latency of thalamic P15 waves, however
      these changes were not present in the group of patients with epilepsy of a
      different origin. CONCLUSIONS: In a group of patients with CSP, dysplastic MRI
      changes, together with the prolongation of thalamic wave latencies according SEP,
      were examined. These clinical symptoms may be considered the result of
      disturbances of early gestation and of lesions of midline structures. CSP became
      an interesting model opportunity for us, and allowed for the clinical, MRI and
      electrophysiological examination of developmental cerebral dysplasias. We believe
      that there is an important role for septal and diencephalic midline structures in
      cerebral electrogenesis, and possibly in the origin of epileptic seizures too.

PMID- 15990726
TI  - The entorhinal cortex regulates blood glucose level in response to microinjection
      of neostigmine into the hippocampus.
AB  - OBJECTIVE: Microinjectin of neostigmine, an inhibitor of acetylcholine esterase,
      into the rat hippocampus elicited stress-like responses reflected by the release
      of adrenocorticotropic hormone (ACTH) and blood glucose elevations. The
      entorhinal cortex is regarded as an interface between the hippocampus and
      neocortex. The current study was designed to examine the role of the entorhinal
      cortex in regulation of blood glucose elevation induced by hippocampal
      neostigmine injection. MATERIAL AND METHODS: We produced the entorhinal cortex
      lesions in 9 week-old male Wistar rats by the bilateral injections of the cell
      selective neurotoxin, ibotenic acid (15microg/microl). Two weeks after the
      injections, neostigmine methylsulfate (sigma, 5x10(-8) mol) was microinjected
      into the rat hippocampus in a volume of 1microl for 1min using a CMA/100
      microinjection pump. Plasma ACTH levels were measured by radioimmunoassay. Plasma
      glucose concentrations were determined by the immobilized enzyme membrane/H2O2
      method with a compact glucose analyzer Antsense II (Bayer Medical Co.Ltd,Tokyo,
      Japan). RESULTS: Compared with sham-operated control rats, the entorhinal lesions
      produced by ibotenic acid significantly attenuated the elevations of blood
      glucose evoked by the microinjection of neostigmine into the hippocampus.
      However, no significant difference of plasma ACTH in response to the injection
      was observed between the entorhinal-lesioned rats and controls. CONCLUSION: The
      results of the present study indicate that the entorhinal cortex plays a role in
      the central nervous systems regulation of blood glucose and may be involved in a
      stress response presumably via an alternative pathway.

PMID- 15990727
TI  - Measurement of protein cytokines in tissue extracts by enzyme-linked
      immunosorbent assays: application to lipopolysaccharide-induced differential
      milieu of cytokines.
AB  - OBJECTIVES: Determination of protein cytokines in local tissues would help to
      evaluate their local role in health, sickness behavior and immune-mediated
      diseases. Therefore, developing a simple quantitative method of protein cytokines
      in tissues/organs is highly important. METHODS: Mouse tissues were collected
      following intraperitoneal administration of endotoxin-free PBS or
      lipopolysaccharide. A mild detergent, 0.1% Igepal, was added in a buffer to
      enhance cytokines extraction. The tissues were then disrupted, homogenized,
      centrifuged and the supernatants were collected and assayed using solid-phase
      immunoassays. RESULTS: The presence of 0.1% Igepal extracted significantly more
      TNF-alpha from liver (322%: p<0.01), brain (358%: p<0.05), lungs (1600%: p<0.01),
      and more IL-10 from liver (220%: p<0.001), brain (4650%: p<0.001) than PBS alone.
      On the other hand, using 0.1% Igepal did not increase IFN-gamma extraction from
      liver, spleen, brain, lungs, skin and kidneys more than PBS alone. Furthermore,
      i.p. administration of LPS induced a differential milieu of cytokines. LPS
      increased significantly the production of TNF-alpha, IFN-gamma, and IL-10 from
      liver (521%, 123%, 72%: p<0.01, 0.04, 0.04), brain (470%, 122%, 280%: p< 0.01,
      0.03, 0.01), peritoneal lavage (p<0.001) and blood (p<0.001). However, the
      pattern of increase was different for the above cytokines in spleen, skin, lungs
      and kidneys. CONCLUSIONS: The extraction of protein cytokines from tissues was
      superior with addition of mild detergent. Furthermore, our results showed a
      differential cytokines response to LPS with respect to tissue and cytokine type.
      This method should provide an important tool for studying local protein cytokines
      in behavioral pattern, sickness behavior, and immune-mediated diseases as well as
      to determine local therapeutic efficacy of immunomodulatory drugs.

PMID- 15990728
TI  - DNA double-helix binds regulatory peptides similarly to transcription factors.
AB  - PROBLEM: Gerontology observations show that ageing of organism is accompanied by
      the decrease of the chromatin activity and slowing down of the protein synthesis.
      Natural regulatory oligopeptides and their synthetic analogues take part in the
      activation of chromatin and normalise rate of the protein synthesis in cultured
      tissues. Regulatory peptides significantly enhance longevity. OBJECTIVES: The
      objective of this work is to find a possible molecular mechanism by which the
      regulatory peptides influence the part of genetic system is responsible for
      initiation of protein synthesis in higher organisms. METHODS: An
      interdisciplinary approach was used to address the problem. The work involved not
      only medical scientists and biologists, but also specialists in biopolymer
      chemistry, and mathematicians for statistical analysis of information interaction
      of amino acid and nucleotide sequences. CONCLUSIONS: The structures and metrics
      of peptides and the DNA double-helix cause the recognition and complementary
      binding of a regulatory peptide with DNA functional groups at the interface of
      the major groove. We have used complementary binding model to find a possible
      base pair sequence ATTTTC for specific binding of synthetic tetrapeptide
      epitalon. This base pair block and its reverse complement were found repeatedly
      in the promoter region of telomerase. A comparison of statistical information
      content of peptides and oligonucleotide sequences shows that these two classes of
      biopolymers are information carriers and. exchange the information to initiate
      the gene transcription.

PMID- 15990729
TI  - Serum markers of inflammation and endothelial activation in children with obesity
      related hypertension.
AB  - OBJECTIVES: It has been suggested that a rise in blood pressure (BP) causes low
      grade inflammation of the endothelium which, in turn, may be responsible for
      further damage of endothelium and worsening of BP control. The aim of the study
      was to evaluate serum levels of inflammation and endothelial activation markers
      in children with obesity-related hypertension and normotensive controls in
      relation to other traditional risk factors of arterial hypertension. METHODS:
      Plasma insulin, glucose, C-reactive protein (CRP), fibrinogen (FB) interleukin-6
      (IL-6), interleukin-1 beta (IL-1 beta), intercellular cell adhesion molecule-1
      (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and lipids levels were
      determined in 50 children with obesity-related hypertension and 143 obese
      children with normal BP. Insulin resistance was assessed by the homeostasis
      model. RESULTS: Children with hypertension had significantly higher levels of all
      inflammatory markers as well as endothelial activation indices compared with
      normotensive subjects. In the stepwise regression model significant independent
      correlates for systolic BP were CRP, FB, VCAM-1, HOMA IR, LDL cholesterol and fat
      mass, whereas CRP, IL-6, ICAM-1, FB, LDL and HDL cholesterol were the
      determinants of diastolic BP in children with obesity-related hypertension.
      CONCLUSION: These results indicate that low-grade inflammation and endothelial
      dysfunction are closely involved in the pathogenesis of obesity-related
      hypertension relatively early in life.

PMID- 15990730
TI  - Further structural analysis of GnRH complexes with metal ions.
AB  - MALDI-TOF mass spectrometry, 1H NMR spectrometry, the continuous variation method
      and molecular modeling by MM3 calculation confirmed our earlier studies showing
      that gonadotropin-releasing hormone (GnRH) forms complex with copper(II) ion with
      the binding ratio 1:1. The copper(II) complex formed at physiological pH has a
      square planar configuration and GnRH complexes with nickel(II) and cobalt(II)
      ions are less stable than that of copper(II).

PMID- 15990731
TI  - Precocious puberty with congenital hypothyroidism.
AB  - Precocious puberty associated with profound hypothyroidism is a rare condition.
      It is usually characterized by breast development, vaginal bleeding, lack of
      pubic hair and delayed bone age. Multicystic ovaries in profound hypothyroid
      patients with precocious puberty have been rarely described. Vaginal bleeding in
      adolescent girls should be considered as a clinical significance particularly
      when it is prolonged or heavy, whereas vaginal bleeding in younger girls,
      regardless of its duration and quantity is always of clinical importance.
      Bleeding in such patients could be caused by local causes such as vulvar or
      vaginal lesions, or it could be from the endometrium, which is usually a sign of
      systemic hormonal disturbance [1]. In this report a rare case of vaginal
      bleeding, large, multicystic ovaries, precocious puberty and delayed bone age in
      a 7 years old girl with profound hypothyroidism is described.

PMID- 15990732
TI  - Sheehan syndrome: clinical and laboratory evaluation of 20 cases.
AB  - Sheehan syndrome (SS) or post-partum pituitary necrosis is a pituitary
      insufficiency secondary to excessive post-partum blood losses. SS is a very
      significant cause of maternal morbidity and mortality in developing countries
      although it is a rarity in developed countries in which obstetrical care has been
      improved. In this study, we reviewed 20 cases retrospectively who were diagnosed
      as SS in our clinic. The patients aged 40 to 65 years with a mean age of 51.12 +/
      9.44 years (mean +/- SD). Time to make a definitive diagnosis of the disease
      ranged between 5 and 25 years with a mean of 16.35 +/- 4.74 years. Three of our
      patient (15%) had a previous diagnosis of SS. Three patients (15%) were referred
      to emergency service for hypoglycemia, three patients (15%) for hypothyroidism
      and one patient (5%) for hyponatremia. Dynamic examination of the pituitary
      revealed GH, Prolactin, FSH, TSH and ACTH insufficiency in all of the patients.
      One of our patients had a sufficient LH response to LHRH challenge. All of the
      patients were imaged with pituitary MRI. Eleven patients had empty sella and 9
      patients had partial empty sella. SS is still a common problem in our country,
      especially in rural areas. Considering the duration of disease, important delays
      occur in diagnosis and treatment of the disease.

PMID- 15990733
TI  - The influence of smoking on plasma folate and lipoproteins in Alzheimer disease,
      mild cognitive impairment and depression.
AB  - The risk for Alzheimer's disease (AD) is associated with lifestyle factors,
      especially cigarette smoking. In this study we investigated the influence of
      smoking on the serum levels of folic acid, LDL and HDL in AD patients, patients
      with minimal cognitive impairment (MCI) and patients with major depression. We
      investigated a total of n = 374 patients in the diagnostic categories:, AD: n =
      272, MCI: n = 60, Major depression: n = 42. We found significantly lower HDL
      levels in smokers and previous smokers in comparison to non-smokers, p<0,05. The
      LDL: HDL ratio in smokers was significant higher (+20%) compared to previous
      smokers and non-smokers, p < 0.05. The mean levels of folic acid were
      statistically significant (p<0.05) lower (-24%) in smokers compared to non
      smokers. Patients with MCI and Alzheimer;s disease (and also major depression)
      who are "smokers" show serum levels of HDL and folic acid that are known to be
      strong risk factors for vascular damage and increased risk for vascular brain
      damage and impaired cognitive function. Therefore cessation of smoking,
      substitution with folate or statin therapy of smoking patients with MCI or AD
      might be beneficial to slow down further cognitive decline.

PMID- 15990734
TI  - Love promotes health.
AB  - Love has consequences for health and well-being. Engaging in joyful activities
      such as love may activate areas in the brain responsible for emotion, attention,
      motivation and memory (i.e., limbic structures), and it may further serve to
      control the autonomic nervous system, i.e., stress reduction. This specific CNS
      activity pattern appears to exert protective effects, even on the brain itself.
      Moreover, anxiolytic effects of pleasurable experiences may occur by promotion of
      an inhibitory tone in specific areas of the brain. Thus, love and pleasure
      clearly are capable of stimulating health, well-being and (re)productivity: This
      wonderful biological instrument makes procreation and maintenance of organisms
      and their species a deeply rewarding and pleasurable experience, thus ensuring
      survival, health, and perpetuation.

PMID- 15990735
TI  - Smoking cessation in patients with coronary artery disease.
AB  - BACKGROUND: Smoking cessation is an important factor in the primary and secondary
      prevention of cardiac events. Although multiple clinical trials have examined the
      efficacy of various smoking cessation aids, a systematic review of the efficacy
      and safety of smoking cessation aids has not been done. METHODS: This paper
      reviews the effects of smoking on coronary artery disease. In addition, we
      identify randomized controlled trials examining the efficacy and safety of
      smoking cessation aids from the years 1970 to 2004. We then pooled the trial
      results for 6- and 12-month rates of continuous smoking abstinence. RESULTS: The
      4 principal mechanisms of cardiovascular damage caused by cigarette smoking are
      induction of a hypercoagulable state, reduction of oxygen delivery because of
      carbon monoxide, coronary vasoconstriction, and nicotine-induced hemodynamic
      effects. Our review of clinical trials suggests that each smoking cessation aid
      improved continuous smoking abstinence rates at both 6 and 12 months compared
      with placebo. The 12-month abstinence rates for the active versus placebo
      treatments were the following: nicotine patch 11.1% versus 5.5%, nicotine gum
      27.3% versus 16.5%, nicotine inhaler 16.9% versus 9.1%, bupropion 18.5% versus
      6.6%, and behavioral therapy 20.0% versus 13.9%. CONCLUSIONS: Several smoking
      related mechanisms are responsible for the development of atherosclerosis and the
      induction of cardiac events. Smoking cessation aids effect a modest increase in
      smoking abstinence at 12 months compared with placebo. In spite the apparent
      success of cessation aids, smoking relapse rates are quite high.

PMID- 15990736
TI  - Cardioprotection before revascularization in ischemic myocardial injury and the
      potential role of hemoglobin-based oxygen carriers.
AB  - Despite the availability of interventional catheterization for patients with
      acute coronary syndromes, there is an unavoidable delay until the occluded
      coronary artery(s) can be revascularized, during which time persistent ischemia
      may lead to irreversible myocardial damage despite subsequently high patency
      rates. Accordingly, there has been an intense effort to develop early
      interventions that will preserve the viability of ischemic myocardium before
      revascularization. A number of novel strategies have been studied, including
      hemoglobin-based oxygen carriers. These compounds transport oxygen in the plasma
      to help maintain more normal oxygen delivery to the myocardium supplied by a
      thrombosed vessel, and they also release oxygen to tissue more efficiently than
      intraerythrocytic hemoglobin.

PMID- 15990737
TI  - Attenuation of reperfusion microvascular ischemia by aqueous oxygen: experimental
      and clinical observations.
AB  - It is being increasingly recognized that, in patients with acute myocardial
      infarction, angiographically successful recanalization of the occluded artery
      cannot be used as a reliable indicator of successful myocardial perfusion.
      Postischemic myocardial reperfusion is commonly associated with focal regions of
      microvascular impairment, even when global coronary artery flow is normal. This
      problem ranges in severity from microvascular stunning to no reflow, depending
      principally on the duration and severity of ischemia. Reperfusion microvascular
      ischemia is not an instantaneous single event that occurs just at the moment of
      reperfusion. Rather, it is a progressive process that increases with time. Of
      importance, it is associated with poor recovery of left ventricular (LV) function
      and a worsened clinical outcome at follow-up. An increasing body of experimental
      and clinical data suggests a valuable role for high concentrations of oxygen
      (O2), delivered directly to the coronary artery, in reducing microvascular
      injury. Recently, a catheter-based method has been developed for infusion of O2 ,
      dissolved in a crystalloid solution at extremely high concentrations (ie, 1-3 mL
      O2 /g [aqueous oxygen {AO}]), into blood without bubble formation to provide
      hyperoxemic treatment of tissue ischemia. In experimental studies, AO hyperoxemia
      has been found to improve LV function and electrocardiographic evidence of
      ischemia. This is thought to be the result of augmentation of oxygen delivery in
      plasma. Marked improvement in myocardial flow has been consistently found. These
      observations may explain the improvement of LV function after AO treatment noted
      in clinical studies.

PMID- 15990738
TI  - Glucose-insulin-potassium and reperfusion in acute myocardial infarction:
      rationale and design of the Glucose-Insulin-Potassium Study-2 (GIPS-2).
AB  - BACKGROUND: The combination of reperfusion therapy and high-dose glucose-insulin
      potassium (GIK) infusion seems beneficial in acute myocardial infarction (MI).
      Current evidence, however, is not considered conclusive. STUDY DESIGN: The
      Glucose-Insulin-Potassium Study-2 (GIPS-2) will investigate whether GIK, in
      adjunction to reperfusion therapy, is beneficial in MI patients without signs of
      heart failure at admission. A total of at least 1044 patients with an acute MI
      treated with either thrombolysis or primary percutaneous coronary intervention
      will be randomized to an infusion of high-dose GIK or no infusion. The primary
      end point of the study is 30-day mortality. Secondary end points are mortality at
      1 year, recurrence of MI, repeat intervention, and infarct size. IMPLICATIONS: If
      high-dose GIK significantly reduces mortality at 30 days in all patients, the
      adjunction of this treatment to reperfusion therapy may become part of standard
      regimen for patients with acute MI without heart failure.

PMID- 15990739
TI  - INvestigation of STEnt grafts in patients with type B Aortic Dissection: design
      of the INSTEAD trial--a prospective, multicenter, European randomized trial.
AB  - PURPOSE: This study describes the design of an ongoing randomized trial initiated
      to compare the 2-year outcome of uncomplicated type B aortic dissection when
      treated by endovascular implantation of a Medtronic Talent stent graft adjunctive
      to best medical treatment versus best medical treatment alone. METHODS: Patients
      older than 18 years with type B aortic dissection as diagnosed by computed
      tomography or magnetic resonance angiography are randomized to either a thoracic
      aortic endoprosthesis and antihypertensive treatment, called "stent grafting," or
      a tailored antihypertensive treatment, called "medical treatment." Only patients
      in a clinically stable condition and without spontaneous thrombosis of the false
      lumen after 14 days of the index dissection are considered eligible for study
      inclusion. RESULTS: Primary outcome measure is all-cause mortality. Secondary
      outcome variables include conversion to stent and/or surgery, induced thrombosis
      of the false lumen, cardiovascular morbidity, aortic expansion (>5 mm/y of
      maximum diameter including true and false lumina), quality of life, and length of
      intensive care unit and hospital stay. The study design calls for 136 patients to
      be randomized and monitored for 24 months. CONCLUSIONS: The INSTEAD trial is the
      first randomized trial investigating the role of endoluminal treatment of
      uncomplicated type B aortic dissection. By the end of December 2004, 125 patients
      were randomized, accounting for 92% of the target. Final results of the INSTEAD
      trial should be available in 2006.

PMID- 15990740
TI  - Predictors of response to cardiac resynchronization therapy (PROSPECT)--study
      design.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is currently indicated in
      patients with moderate to severe heart failure, a wide QRS complex and
      significant left ventricular dysfunction despite optimal medical therapy.
      Adoption of these criteria for CRT results in a favorable response in only two
      thirds of candidates. METHODS: "Predictors of response to cardiac
      resynchronization therapy (PROSPECT)," a prospective, multicenter, nonrandomized
      study, aims to identify echocardiographic measures of dyssynchrony and evaluate
      their ability to predict response to CRT. PROSPECT will enroll approximately 300
      patients in up to 75 centers in the United States, Asia, and Europe with clinical
      follow-up for 6 months. We will prospectively and individually test a variety of
      conventional echocardiographic and tissue Doppler imaging parameters against
      measures of clinical response. The primary response criteria are improvement in
      the heart failure Clinical Composite Score and left ventricular reverse
      remodeling. Enrollment began in March 2004 and is expected to conclude early
      2005.

PMID- 15990741
TI  - Risk factors for cardiovascular event recurrence in the Atherosclerosis Risk in
      Communities (ARIC) study.
AB  - BACKGROUND: Numerous studies have identified risk factors and markers associated
      with incidence of cardiovascular disease (CVD). However, few studies have
      examined whether established risk factors, novel blood markers, carotid
      ultrasonography, or ankle-brachial index can predict recurrent CVD events.
      METHODS AND RESULTS: We analyzed the relation of established risk factors and
      markers of atherosclerosis with the risk of recurrent CVD in 766 participants.
      Over a mean of 8.7 years of follow-up, 70 women and 243 men had a recurrent CVD
      event (85.3% coronary heart disease and 23.7% stroke). Adjusting for age and sex,
      this study found that established risk factors were associated with recurrent CVD
      events in the anticipated direction. Being in the highest (vs lowest) quartiles
      of lipoprotein (a), fibrinogen, white blood cells, and creatinine at baseline
      were associated with 47%, 69%, 65%, and 81%, respectively, greater risk of a CVD
      event, and being in the highest quartile of albumin was associated with 39% lower
      risk. Being in the highest (vs lowest) quartile of carotid intima-media thickness
      (IMT) was associated with a doubling of risk, and having carotid plaque with
      acoustic shadowing (vs having no plaque) was associated with 83% increased risk
      of a CVD event. After adjustment for established risk factors, creatinine,
      albumin, and carotid IMT in the highest quartile (vs lowest quartile) and carotid
      plaque with acoustic shadowing (vs no plaque) were independently associated with
      recurrent CVD events. CONCLUSION: Established risk factors, but only a few of
      novel risk factors and markers, were independent predictors of recurrent CVD
      events.

PMID- 15990742
TI  - Are we appropriately triaging patients with unstable angina?
AB  - BACKGROUND: It is uncertain how aggressively patients should be monitored and
      admitted to the hospital for chest pain syndromes and if the monitoring itself
      affects patient care, process, or outcomes. We assessed the appropriateness of
      care based on retrospective analysis of admission bed assignment (nonmonitored vs
      monitored) and Thrombolysis in Myocardial Infarction (TIMI) risk score in
      patients from the Global Unstable Angina Registry and Treatment Evaluation
      (GUARANTEE) Registry. METHODS: Baseline characteristics, process of care, and
      outcomes were compared among 2939 patients admitted to 1 of 35 hospitals in the
      United States. Patients were stratified into low (0-2), intermediate (3 or 4),
      and high (5-7) risk based on TIMI risk score. RESULTS: Among the patients, 92
      (3%) were admitted to the cardiac care unit (CCU), 1602 (56%) were admitted to
      the telemetry unit, and 1163 (41%) were admitted to an unmonitored bed.
      Paradoxically, high-risk patients comprised only 1% of those in the CCU, 5% of
      those in telemetry, and 10% of those in nonmonitored units. Conversely, low-risk
      patients were 64% of those in the CCU, 53% of those in telemetry, and 42% of
      those in unmonitored beds. Procedures were done more often on patients admitted
      to nonmonitored units than those on telemetry or in the CCU irrespective of TIMI
      risk score. CONCLUSIONS: This registry suggests that triage of patients does not
      routinely follow the risk-based approach suggested in the American College of
      Cardiology and American Heart Association guidelines and could therefore
      potentially lead to inefficiencies in care. Better implementation of risk
      stratification for acute coronary syndrome evaluation and management is
      necessary.

PMID- 15990743
TI  - An acute inflammatory reaction induced by myocardial damage is superimposed on a
      chronic inflammation in unstable coronary artery disease.
AB  - BACKGROUND: Inflammation plays an important role in unstable coronary artery
      disease (CAD). We assessed the kinetics of inflammatory markers from symptom
      onset in patients with unstable CAD and their relation to myocardial damage.
      METHODS: Serial measurements of inflammatory mediators were performed in
      consecutive patients with unstable CAD enrolled at selected sites in the FRISC II
      (n = 558) and the GUSTO IV (n = 404) trials. The time from symptom onset was
      calculated for every serum sample (total 4400 samples). RESULTS: Median levels of
      interleukin 6 and C-reactive protein reached their peaks at 36 to 42 hours and at
      48 to 54 hours, respectively, from symptom onset and returned to early
      postsymptom levels within 6 weeks. The early increase occurred almost exclusively
      in patients with baseline troponin T elevation (>0.01 microg/L). In contrast,
      median levels of fibrinogen increased continuously up to 120 hours after symptom
      onset, independently of myocardial damage. At 6 months, fibrinogen levels were
      still higher than in the early phase after symptom onset. The median levels of
      interleukin 6, C-reactive protein, and fibrinogen were still higher at 6 months
      than in healthy controls matched for age and sex to a population with unstable
      CAD. CONCLUSIONS: An early acute inflammatory reaction induced by myocardial
      damage seems to be superimposed on a chronic inflammatory condition, both of
      which might influence long-term outcome in unstable CAD.

PMID- 15990744
TI  - Prevalence of metabolic syndrome in cardiac rehabilitation/secondary prevention
      programs.
AB  - BACKGROUND: Metabolic syndrome (MS) consists of a cluster of obesity-related risk
      factors that have been linked to the development and progression of coronary
      heart disease (CHD). The purpose of this study was to examine the prevalence of
      MS, as defined by the National Cholesterol Education Program Expert Panel on
      Detection, Evaluation, and Treatment of High Blood Cholesterol, in patients with
      CHD attending cardiac rehabilitation (CR) after a coronary event. METHODS: We
      analyzed baseline data of 1912 individuals with established coronary artery
      disease entering CR in Burlington, Vt, and Boston, Mass. RESULTS: Overall, 50% of
      patients entering CR have MS. A significantly greater percentage of women than
      men have MS (54% vs 48, respectively, P < .001). This is due to higher prevalence
      of abdominal obesity, high triglycerides, and hypertension (all, P < .05) in
      women. In women, the prevalence of MS peaked in the eighth decade vs the fifth
      decade in men. CONCLUSIONS: The prevalence of MS in patients with CHD
      participating in CR is greater than twice that of the general population. The
      prevalence of MS is higher and occurs at an older age in women than men. This
      study highlights the need for CR programs to develop specific interventions to
      assist patients with risk factor modification primarily by targeting physical
      inactivity and weight control.

PMID- 15990745
TI  - Chromium supplementation shortens QTc interval duration in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: We investigated the potential effects of chromium supplementation on
      QTc interval duration in type 2 diabetic patients. METHODS: Of 60 patients with
      type 2 diabetes mellitus, 30 were randomly assigned to group A, and 30 to group
      B. Group A received 1000 microg of chromium picolinate (CrPic) daily for 3
      months, followed by placebo in the next 3 months; group B was treated with
      placebo for the first 3 months and CrPic in the next 3 months. At each visit, QT
      interval was measured on a standard electrocardiogram by averaging 3 consecutive
      beats in leads II and V4 and corrected for heart rate with Bazett formula.
      RESULTS: Although baseline QTc interval was similar in both groups (422 +/- 34
      milliseconds in group A vs 425 +/- 24 milliseconds in group B, P = .77), QTc
      interval at 3 months was shorter in group A (406 +/- 35 milliseconds) than in
      group B (431 +/- 26 milliseconds, P = .01). In the following 3 months, QTc
      interval shortened in group B but not in group A, which resulted in a comparable
      QTc interval duration of both groups at the end of the study (414 +/- 28
      milliseconds in group A vs 409 +/- 22 milliseconds in group B, P = .50). Apart
      from body mass index (31.4 +/- 4.2 kg/m2 in patients with QTc shortening vs 28.7
      +/- 4.2 kg/m2 in patients without QTc shortening, P = .03), none of the clinical
      and laboratory variables predicted QTc interval shortening in our patient cohort.
      CONCLUSIONS: Short-term chromium supplementation shortens QTc interval in
      patients with type 2 diabetes mellitus.

PMID- 15990746
TI  - Economic analysis of the Assessment of the Safety and Efficacy of a New
      Thrombolytic Regimen (ASSENT-3) study: costs of reperfusion strategies in acute
      myocardial infarction.
AB  - BACKGROUND: The ASSENT-3 study examined the safety and efficacy of 3 alternative
      regimens for ST-elevation acute myocardial infarction: full-dose tenecteplase
      (TNK-tPA) plus enoxaparin; half-dose TNK-tPA plus unfractionated heparin plus
      abciximab; and full-dose TNK-tPA plus unfractionated heparin. OBJECTIVE: The aim
      of the study was to examine the resource and economic effects of the 3 regimens
      in ASSENT-3 using empirically collected data from the trial. METHODS: Cost
      estimates for each resource use component collected in ASSENT-3 were derived from
      Medicare reimbursement rates and from detailed billing data collected as part of
      a previous study. Costs of study drugs were estimated using average wholesale
      prices. All analyses were by intention to treat. Resource use and medical costs
      were examined first in the United States alone, and then in the entire cohort.
      RESULTS: Differences in costs across treatment arms were primarily due to
      differences in cost of study medication. Irrespective of source of cost weights,
      the least expensive alternative among the 3 treatment regimens was TNK-tPA and
      enoxaparin. Although not statistically significant, in 80% of 1000 bootstrap
      replications, the TNK-tPA enoxaparin arm was associated with 30-day cost savings
      relative to the unfractionated heparin arm. CONCLUSION: The favorable clinical
      outcomes demonstrated for enoxaparin arm relative to the unfractionated heparin
      arm in ASSENT-3 were accompanied by a favorable distribution of costs and support
      the designation of this regimen as economically attractive by conventional
      benchmarks.

PMID- 15990747
TI  - Clinical factors that influence response to treatment strategies in atrial
      fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm
      Management (AFFIRM) study.
AB  - BACKGROUND: The AFFIRM Study was a randomized multicenter comparison of 2
      treatment strategies, rate-control versus rhythm-control, in high-risk patients
      with atrial fibrillation (AF). The primary outcome of the trial showed no overall
      difference in survival between strategies. However, there may be important
      patient subgroups for which there are identifiable differences in outcome with 1
      of the 2 strategies. METHODS AND RESULTS: Subgroups that were prespecified for
      analysis from the main AFFIRM Study were age, sex, coronary artery disease (CAD),
      hypertension, congestive heart failure (CHF), left ventricular ejection fraction
      (LVEF), rhythm at randomization, first episode of AF, and duration of the
      qualifying episode of AF. Baseline characteristics were analyzed for each
      subgroup. Adjusted hazard ratios for each subgroup and for each stratum were
      generated using Cox models, and these models were used to determine whether
      treatment strategy affected overall survival differentially by subgroup. Adjusted
      survival was worse for patients > or =65 years and for patients with a history of
      CHF, CAD, or an abnormal LVEF. In the adjusted analyses, the effect of treatment
      strategy was similar within all of the prespecified subgroups. When each subgroup
      stratum was analyzed separately, patients > or =65 years and patients without a
      history of CHF had significantly better outcome with rate-control therapy (each P
      < .01). CONCLUSIONS: Overall, treatment effect for rate control versus rhythm
      control was the same within each subgroup. However, certain selected patient
      categories may have better survival with one particular strategy for management
      of AF.

PMID- 15990748
TI  - Factors affecting bleeding risk during anticoagulant therapy in patients with
      atrial fibrillation: observations from the Atrial Fibrillation Follow-up
      Investigation of Rhythm Management (AFFIRM) study.
AB  - BACKGROUND: Stroke and systemic thromboembolism are serious problems for patients
      with atrial fibrillation (AF), but their incidence can be substantially reduced
      by appropriate anticoagulation. Bleeding is the major complication of
      anticoagulant treatment, and the relative risks for bleeding vs stroke must be
      considered when starting anticoagulation. METHODS: The AFFIRM trial included
      patients with AF and at least one risk factor for stroke, randomly assigning them
      to either a rate-control or rhythm-control strategy. All patients were initially
      treated with warfarin. The incidence of protocol-defined major and minor bleeding
      was documented during follow-up. Variables associated with bleeding were
      determined using a Cox proportional hazards model, using baseline and time
      dependent covariates. RESULTS: The 4060 patients in the AFFIRM trial were
      followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an
      annual incidence of approximately 2% per year, with no significant difference
      between the rate-control and rhythm-control groups. Increased age, heart failure,
      hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin
      use were significantly associated with major bleeding. Minor bleeding was common
      in both treatment arms, with 738 patients reporting this problem in one or more
      visits. CONCLUSIONS: Bleeding is a significant problem that complicates
      management of patients with AF. Risk factors for bleeding can be identified, and
      knowledge of these risk factors can be used to plan therapy.

PMID- 15990750
TI  - Concerns about the implantable cardioverter defibrillator: a determinant of
      anxiety and depressive symptoms independent of experienced shocks.
AB  - BACKGROUND: Patients with an implantable cardioverter defibrillator (ICD) are at
      increased risk of anxiety disorders. In turn, anxiety has been identified as a
      precipitant of ventricular arrhythmias. Anxiety may in part be attributed to
      concerns about the ICD firing, but the relationship between ICD concerns,
      psychological morbidity, and shocks has not been systematically investigated. We
      examined the relative importance of experienced shocks versus subjective concerns
      about the ICD as determinants of anxiety and depressive symptoms in ICD patients.
      METHODS: Consecutive surviving patients ( n = 182, response rate = 82%) having
      had an ICD implanted between October 1998 and January 2003 at the Erasmus Medical
      Centre Rotterdam were asked to fill in the ICD Patient Concerns Questionnaire and
      the Hospital Anxiety and Depression Scale. Clinical variables were obtained from
      the patients' medical records. RESULTS: A total of 55 (30%) patients had received
      a shock from the ICD. Although patients who had experienced a shock scored higher
      on ICD concerns, ICD concerns was the only independent determinant of anxiety
      (odds ratio 6.35, 95% CI 2.84-14.20) and depressive symptoms (odds ratio 2.29,
      95% CI 1.06-4.96) adjusting for shocks and all other factors. CONCLUSIONS:
      Patient concerns about the ICD may be an important indicator of psychosocial
      adjustment. Screening for ICD patient concerns using the ICD Patient Concerns
      Questionnaire may identify patients at risk for psychological morbidity after ICD
      implantation.

PMID- 15990749
TI  - Asymptomatic atrial fibrillation: demographic features and prognostic information
      from the Atrial Fibrillation Follow-up Investigation of Rhythm Management
      (AFFIRM) study.
AB  - BACKGROUND: Atrial fibrillation (AF) may occur without symptoms. Little is known
      about demographic features and prognostic information in patients with
      asymptomatic AF. METHODS: In the AFFIRM study, 4060 patients were randomized to
      either rhythm or rate control. At baseline, patients were identified as
      asymptomatic if they answered "no" to a 15-item questionnaire related to cardiac
      symptoms during AF in the 6 months before study entry. RESULTS: There were 481
      (12%) asymptomatic patients at baseline. Compared with symptomatic patients,
      asymptomatic patients were more often men and had a lower incidence of coronary
      artery disease and congestive heart failure, but had more cerebrovascular events.
      Asymptomatic patients had a longer duration of AF, a lower maximum heart rate,
      and better left ventricular function. They received fewer cardiac medications and
      fewer therapies to maintain sinus rhythm. At 5 years, there was a trend for
      better survival in asymptomatic patients (81% vs 77%, P = .058), and they were
      more likely to be free from disabling stroke or anoxic encephalopathy, major
      bleeding, and cardiac arrest (79% vs 67%, P = .024). However, mortality and major
      events were similar after correction for baseline differences. CONCLUSIONS:
      Patients with asymptomatic AF have less serious heart disease but more
      cerebrovascular disease. Asymptomatic patients receive different therapies than
      symptomatic patients. However, the absence of symptoms and the differences in
      treatment does not confer a more favorable prognosis when differences in baseline
      clinical parameters are considered. Anticoagulation should be considered in these
      patients.

PMID- 15990751
TI  - Incidence, predictors, and outcomes of high-degree atrioventricular block
      complicating acute myocardial infarction treated with thrombolytic therapy.
AB  - BACKGROUND: In the fibrinolytic era, several studies have suggested that the rate
      of atrioventricular block (AVB) in the setting of acute myocardial infarction
      (MI) is high and is associated with increased short-term mortality. We sought to
      delineate predictors of AVB and determine long-term mortality of patients
      developing AVB in the setting of ST-segment elevation MI (STEMI) treated with
      thrombolytic therapy. METHODS: We combined data on patients from 4 similar
      studies of STEMI. We identified independent predictors of AVB and compared the 6
      month and 1-year mortality rates of patients with AVB (5251) to the rates of
      patients without AVB (70 742). RESULTS: The incidence of AVB was 6.9%.
      Significant independent predictors of AVB included inferior MI, older age, worse
      Killip class at presentation, female sex, enrollment in the United States,
      current smoking, hypertension, and diabetes. Adjusted mortality was significantly
      higher in patients with AVB than in patients without AVB within 30 days (OR 3.2,
      95% CI 2.7-3.7), 6 months (OR 1.6, 95% CI 1.5-1.8), and 1 year (OR 1.5, 95% CI
      1.3-1.6). For patients with AVB and inferior MI, mortality odds ratios (ORs) were
      2.2 (95% CI 1.7-2.7), 2.6 (95% CI 2.4-2.9), and 2.4 (95% CI 2.2-2.6) within 30
      days, 6 months, and 1 year, respectively. For patients with AVB and anterior MI,
      mortality ORs were 3.0 (95% CI 2.2-4.1), 3.5 (95% CI 3.1-3.8), and 3.3 (95% CI
      3.0-3.7) within 30 days, 6 months, and 1 year, respectively. CONCLUSIONS: In the
      thrombolytic era, AVB in the setting of STEMI is common and associated with
      higher mortality. Future studies should focus on determining therapies that are
      effective at reducing mortality rates in such patients.

PMID- 15990752
TI  - The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in
      vitro aspirin resistance in patients with intracoronary stent restenosis.
AB  - OBJECTIVES: The aim of our study was to determine the relation between platelet
      glycoprotein IIIa (Pl A ) polymorphism and aspirin resistance in patients with
      intracoronary stent restenosis. BACKGROUND: Clinically, aspirin resistance is
      defined as having thrombotic and embolic cardiovascular events despite regular
      aspirin therapy. Platelet glycoprotein IIIa polymorphism is said to be a possible
      mechanism of aspirin resistance. METHODS: We studied the prevalence of aspirin
      resistance in 204 previously intracoronary stent-implanted patients with stable
      coronary artery disease. In 102 of these patients, intracoronary stent restenosis
      was present. Platelet functions were analyzed in a platelet function analyzer
      (PFA-100, Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and
      collagen and/or adenosine diphosphate cartridges. Closure time <186 seconds was
      defined as aspirin resistance with Col/Epi cartridges of PFA-100. The Pl A
      polymorphisms of 43 aspirin-resistant and 51 aspirin-sensitive subjects were
      determined with polymerase chain reaction and restriction fragments length
      polymorphism. RESULTS: A total of 31.3% (n = 32) of patients with intracoronary
      stent restenosis and 10.7% (n = 11) of patients with patent intracoronary stents
      were resistant to aspirin by PFA-100. The Pl A1,A1 allele of glycoprotein IIIa
      was present in 36 subjects (83.7.%) and the Pl A1,A2 allele was present in 7
      subjects (16.2.%) in the aspirin-resistant patients group. The Pl A1,A1 allele of
      glycoprotein IIIa was present in 37 subjects (72.5%) and the Pl A1,A2 allele was
      present in 14 subjects (27.5%) in the aspirin-sensitive patients group ( P =
      .195). CONCLUSION: Our results suggest that platelets of patients with
      intracoronary stent restenosis with or without Pl A2 heterozygosity of
      glycoprotein IIIa are more likely to be resistant to low-dose aspirin therapy.

PMID- 15990754
TI  - Two-year clinical follow-up of 90Sr/90 Y beta-radiation versus placebo control
      for the treatment of in-stent restenosis.
AB  - BACKGROUND: It is an ongoing concern that intracoronary brachytherapy may
      possibly just delay the problem of in-stent restenosis ("late catch up"). For
      gamma-radiation, 3 placebo-controlled studies have shown the maintenance of the
      initially positive effect after 2 years, but similar data do not exist for beta
      radiation. STents And Restenosis Trial (START) was the first placebo-controlled
      randomized trial for in-stent restenosis with beta-radiation; herein, we report
      the 2-year clinical follow-up. METHODS AND RESULTS: Two hundred and forty-four
      patients were randomized to active treatment, 232 patients to placebo (nonactive
      source train) treatment. The primary end point of efficacy was target vessel
      revascularization (TVR); primary safety end point was any major adverse cardiac
      event (MACE) at 8 months and 2 years. Two-year clinical outcome in patients
      receiving brachytherapy was based on 195 of 244 original patients (79.9%) and in
      the placebo arm on 183 of 232 original patients (78.9%). TVR was significantly
      reduced by 25%; from 36.6% (placebo) to 27.5% (brachytherapy) remained
      significant after 2 years (RR .7 [.57-.98], 95% CI -9.2 [-17.5-0.8]). The Kaplan
      Meier analysis for TVR and MACE showed improvement beginning approximately 90
      days after radiation and remained almost constant for the 2 following years.
      Freedom from TVR was significantly increased from 62.4% +/- 3.8% to 71.6% +/-
      3.3% (P = .027) and freedom from MACE from 58.9% +/- 3.7% to 68.0% +/- 3.4% (P =
      .035). CONCLUSIONS: The START trial shows for the first time that the initial
      beneficial effects of intracoronary brachytherapy with beta-radiation using 90
      Sr/ 90 Y are maintained at 2-year clinical follow-up period.

PMID- 15990753
TI  - Prospective randomized comparison of early and late results of a carbonized stent
      versus a high-grade stainless steel stent of identical design: the PREVENT Trial
      [corrected].
AB  - BACKGROUND: Restenosis after coronary interventions with stent implantation is
      still the main obstacle of interventional cardiology. The aim of this study was
      to compare a carbonized and high-grade stainless steel stent of identical design
      with regard to early and late adverse events. METHODS: In this prospective
      randomized trial the carbonized MAC stent (amg GmbH, Raesfeld-Erle, Germany) was
      compared with the stainless steel MAC stent of identical design. Primary end
      point was diameter stenosis at follow-up; secondary end points were angiographic
      parameters, rate of restenosis, and major cardiac adverse events (MACE;
      myocardial infarction, reintervention, and death). RESULTS: Between August 1999
      and June 2002, 396 patients were randomized in 2 centers of Germany. Diameter
      stenosis at follow-up (38.6% +/- 23.4% vs 39.1% +/- 22.2%, P = .49) as primary
      end point, relative late lumen loss (26.8% +/- 23.7% vs 27.7% +/- 22.3%, P =
      .26), absolute late lumen loss (0.92 +/- 0.71 vs 0.92 +/- 0.66 mm, P = .58), net
      gain (1.4 +/- 0.8 vs 1.4 +/- 0.8 mm, P = .96), as well as restenosis rates (18.0%
      vs 19.0%, P = .81) and MACE (13.5% vs 12.2%, P = .71) were not significantly
      different between the carbonized and the pure stainless steel study arm,
      respectively. CONCLUSION: The hypothesis of superiority of the carbonized stent
      over a stainless steel stent of identical design with regard to restenosis and
      MACE could not be proved. Inactive coating of stents seems to have no advantage
      over pure stainless steel stents, which was also demonstrated in other trials.
      The future probably lies in active coating of stents with drugs that reduce the
      neointimal proliferation process.

PMID- 15990755
TI  - Diabetes and progression of coronary calcium under the influence of statin
      therapy.
AB  - BACKGROUND: Coronary artery calcium (CAC) is a sensitive marker for the detection
      of coronary heart disease (CHD). Coronary artery calcification can be accurately
      quantified using electron beam tomography (EBT). We sought to evaluate the
      progression of atherosclerosis in asymptomatic persons with type 2 diabetes and
      measure the influence of statin therapy on CAC progression. METHODS: We evaluated
      163 asymptomatic patients with type 2 diabetes (120 men, 43 women). Patients were
      physician referred and underwent 2 consecutive EBT scans at least 1 year apart.
      Demographic data, risk factors for CHD, and medication use were collected.
      Patients with symptoms or known CHD were excluded. RESULTS: The mean age was 65
      +/- 10 years. The mean CAC score at baseline was 651 +/- 414. Only 9 (6%) of 163
      of participants had scores of 0 at baseline. The time between scans averaged 27
      +/- 15 months. Patients not treated with statins demonstrated a median annual
      increase in CAC progression of 20% (4%-44%), whereas statin-treated patients
      demonstrated increase of 10% (4%-25%) (P = .0001). Hemoglobin A 1c was weakly
      associated with CAC progression. CONCLUSIONS: Asymptomatic diabetic patients show
      a high prevalence of atherosclerosis based on high frequency of coronary
      calcification. Statin therapy induced a 50% reduction in the rate of CAC
      progression. As rapid CAC progression has been associated with coronary events,
      EBT may serve as a noninvasive method for following atherosclerosis and response
      to therapy.

PMID- 15990756
TI  - Safety and accuracy of multidetector row computed tomography for early assessment
      of residual stenosis of the infarct-related artery and the number of diseased
      vessels after acute myocardial infarction.
AB  - BACKGROUND: Recent studies reveal that contrast-enhanced multidetector row
      computed tomography (MDCT) is a promising technique for noninvasive visualization
      of coronary artery stenoses. We investigated the safety and accuracy of MDCT for
      early assessment of the severity of residual stenosis of the infarct-related
      artery (IRA) and the number of diseased vessels in patients after acute
      myocardial infarction (AMI). METHODS AND RESULTS: Of 146 AMI cases admitted, 72
      fit with criteria and underwent 16-slice MDCT (4 +/- 2 days after AMI) with beta
      blockers. There were no complications except 1 patient who had from complete
      atrioventricular block. Results were compared with conventional coronary
      angiography (CCA) within 3 days. In 55 (73.3%) of 72 patients, all arteries were
      assessable. In total, the number of assessable arteries was 253 (87.8%), and 35
      (12.2%) vessels were nonassessable, mostly because of motion artifacts and
      extensive calcification. Overall, 84 of the 115 lesions (> or = 50% lumen
      reduction) were correctly detected by MDCT (sensitivity 73.0%). The accuracy in
      classifying patients with nonsignificant, single-, or multiple-vessel diseases
      was 79.1%. The accuracy for residual lesions with >50% stenosis of IRA was 87.5%.
      There was a good correlation regarding the severity of residual stenosis of the
      IRA (0%, 1%-49%, 50%-89%, 90%-99%, or occlusion) between MDCT and CCA (Spearman
      correlation 0.94, P < .001). Lesions with 90% to 99% or occlusion of the IRA were
      accurately detected or ruled out in 31 of 36 cases (86.1%). CONCLUSIONS: With
      appropriate protocol, MDCT is safe and accurate in assessing the severity of IRA
      and the number of diseased vessels during the first week after AMI. It has the
      potential to provide triage for early management of patients after AMI.

PMID- 15990757
TI  - Electrocardiographic diagnosis of left ventricular hypertrophy: the effect of
      left ventricular wall thickness, size, and mass on the specific criteria for left
      ventricular hypertrophy.
AB  - BACKGROUND: The purpose of our study was to determine the relative importance and
      effect of an increased left ventricle wall thickness, left ventricular diastolic
      diameter, and left ventricular mass (LVM) on the performance of the 4 major
      electrocardiogram (ECG) criteria of left ventricular hypertrophy (LVH) and to
      determine how these findings could be incorporated into the routine ECG
      interpretation of LVH. METHODS: The ECG criteria of LVH that we chose to examine
      were voltage, repolarization abnormalities, left atrial abnormality, and
      ventricular conduction time. We analyzed data from 608 consecutive patients with
      left ventricular wall thickness of >13 mm on the echocardiogram and with a
      concurrent ECG. We arbitrarily divided patients into 3 groups (groups I-III)
      according to the calculated LVM. Group I had an LVM of <400 g; group II had an
      LVM from 400 to 600 g, and group III had an LVM of >600 g. We evaluated the
      effect of increasing LVM, wall thickness, and ventricular diameter on the
      performance of the 4 ECG criteria at different severity of thickness, diameter,
      and mass. RESULTS: An increase in the echocardiogram-derived LVM had significant
      effect on all 4 ECG criteria. As LVM progressively increased from groups I to
      III, the frequency of voltage criteria for LVH increased from 52% to 83%; left
      atrial abnormality rose from 46% to 68%; ST-T wave changes increases from 55% to
      95%, and QRS prolongation significantly increased from 42% to 70%. CONCLUSION:
      Increased wall thickness and ventricular diameter failed to correlate with the
      overall ECG score or significantly influence the frequency of any of the 4 ECG
      criteria for LVH in patients when LVM was held relatively constant. We also
      demonstrated that an increasing number of criteria on the ECG are associated with
      a greater mean LVM.

PMID- 15990758
TI  - Intensity and focus of heart failure disease management after hospital discharge.
AB  - BACKGROUND: Although features of heart failure disease management programs are
      broadly outlined, little is known about which interventions are actually used in
      the outpatient setting or which patients are most likely to require
      interventions. METHODS AND RESULTS: Between September 2001 and June 2002, we
      enrolled 32 patients admitted to the Brigham and Women's Hospital Heart Failure
      Services, Boston, Mass, with decompensated heart failure. The intensity of care
      and outcomes of these patients were prospectively tracked for more than 90 days.
      During this time, there were 325 patient contacts (median 8.5 per patient),
      including 247 calls (median 7 per patient) and 78 clinic visits (median 2 per
      patient). Brigham and Women's Hospital clinicians adjusted diuretics a total of
      109 times (median 2.5 times per patient). When frequency of diuretic adjustments
      was used to estimate the intensity of care, higher values of blood urea nitrogen
      at discharge predicted an increased intensity of care during the 90-day follow-up
      (relative risk [RR] 1.2, 95% confidence interval [CI] 1.0-1.3, P = .02). When
      frequency of clinic visits, telephone calls, and diuretic adjustments were used
      to estimate intensity of care, discharge creatinine (RR 1.03, 95% CI 0.99-1.06, P
      = .05), discharge blood urea nitrogen (RR 1.13, 95% CI 1.04-1.23, P = .004), and
      length of stay (RR 1.07, 95% CI 1.00-1.13, P = .04) were predictors of the
      composite end point. CONCLUSIONS: Even after undergoing optimization of
      medications during admission for acute heart failure, patients in a comprehensive
      disease management program required frequent interventions to maintain clinical
      stability. Renal dysfunction was the strongest predictor of increased
      interventions and worse outcome.

PMID- 15990759
TI  - Metaanalysis and review of heart failure disease management randomized controlled
      clinical trials.
AB  - BACKGROUND: The medical community has turned to disease management (DM) to bridge
      the gap between proven therapies and clinical practice for patients with heart
      failure (HF). The aim of this study was to assess the effectiveness of DM
      programs in reducing hospitalization and mortality in patients with HF on the
      basis of the results of existing trials. METHODS: We compared the published
      results from 19 randomized controlled clinical trials evaluating HF DM programs.
      A random effects model was used to combine the hazards ratio for all-cause
      hospitalization across the studies evaluating specific types of HF DM programs.
      RESULTS: We identified 19 relevant studies, with 5752 enrolled patients, which
      assessed the benefits of HF DM programs. The overall effect was a significant
      decrease in all-cause hospitalization for patients with HF. There was significant
      heterogeneity in the results (P < .0001). CONCLUSIONS: The results of this
      analysis indicate that HF DM is an intervention that could significantly decrease
      hospitalization for patients with HF. However, due to differences in the types of
      strategies and the variety of health care settings in which they were evaluated,
      further studies of HF DM programs with multiple participating centers are
      required.

PMID- 15990760
TI  - Left atrial volumetric remodeling is predictive of functional capacity in
      nonobstructive hypertrophic cardiomyopathy.
AB  - BACKGROUND: The left atrium is afterload sensitive, responding to immediate
      changes in left ventricular (LV) diastolic pressure, and left atrial volumetric
      remodeling has been reported in conditions associated with abnormal diastolic
      function. We examined the relationship between left atrial volumetric remodeling
      and objective measures of exercise capacity in patients with nonobstructive
      hypertrophic cardiomyopathy (HCM). METHODS: We compared LA volume indices, other
      2-dimensional and Doppler echocardiographic parameters, invasive hemodynamic
      measures, and magnetic resonance imaging (MRI)-derived LV mass with exercise
      duration, maximal oxygen uptake (MV* O2), anaerobic threshold (AT), and
      ventilatory efficiency (VE/V* CO2 slope) in 43 patients with nonobstructive HCM.
      Patients underwent cardiac catheterization within 48 hours and metabolic stress
      testing within 1 week of their echocardiogram and MRI examinations. RESULTS: Left
      atrial volume at end-ventricular systole (LA max) and end-atrial emptying (LA
      min) correlated with MV* O2 (r = -0.39, P < .01 for both), AT (r = -0.42, r = 
      0.39, respectively, P < .01 for both), and VE/V* CO2 slope (r = 0.45, P = .003; r
      = 0.41, P = .008). Patients with an LA max > or =33 mL/m2 had significantly lower
      MV* O2 (P = .025) and AT levels (P = .017) and higher VE/V* CO2 slope levels (P =
      .004) as compared with patients with a smaller LA size. In multivariate analysis,
      MRI-determined LV mass, which was not a univariate correlate of exercise
      tolerance, provided additional effect when combined with LA volume index.
      CONCLUSIONS: Left atrial volumetric remodeling predicts exercise capacity in
      nonobstructive HCM and may reflect chronic LV diastolic burden. This simple
      noninvasive measure of LA size may provide a long-term indication of the effects
      of chronically elevated filling pressures in patients with HCM and further
      studies testing its prognostic value are necessary.

PMID- 15990761
TI  - A propensity score analysis of the impact of angiotensin-converting enzyme
      inhibitors on long-term survival of older adults with heart failure and perceived
      contraindications.
AB  - OBJECTIVES: The purpose of this study is to determine the association between
      discharge use of angiotensin-converting enzyme (ACE) inhibitors in patients with
      perceived contraindications to these drugs and 4-year post-discharge survival
      among hospitalized older adults discharged alive with a primary discharge
      diagnosis of systolic heart failure. BACKGROUND: Perceived contraindications to
      the use of ACE inhibitors are often associated with underuse of these life-saving
      drugs. METHODS: Chronic renal insufficiency, hypotension, hyperkalemia, and
      severe aortic stenosis were conditions perceived as contraindications. Using a
      multivariable logistic regression model, we at first determined propensity scores
      for receipt of ACE inhibitors for each patient. Bivariate and multivariable Cox
      proportional hazard analyses were used to determine crude and adjusted risks of 4
      year mortality compared with patients without perceived contraindications who
      were discharged on an ACE inhibitor (referent group). RESULTS: Compared with the
      referent group, patients with perceived contraindications who were not discharged
      on an ACE inhibitor had a significant 2-fold increase in the risk of 4-year
      mortality (adjusted hazard ratio [HR] = 2.33, 95% CI = 1.30-4.19). Patients with
      perceived contraindications who were discharged on ACE inhibitors had a non
      significant 23% higher risk of 4-year mortality (versus the referent group)
      (adjusted HR = 1.23, 95% CI = 0.71-2.13). CONCLUSION: Discharge use of ACE
      inhibitors was associated with significant long-term survival benefit in patients
      considered to have contraindication to these drugs.

PMID- 15990764
TI  - Primary prevention of asthma and allergy.
AB  - The relentless increase in the prevalence of asthma and allergic diseases
      highlights the need for devising effective preventive strategies. Although the
      genetics of these disorders are being investigated, manipulation of known
      environmental risk factors remains the best available approach to this problem.
      However, the large number of potential environmental risk factors and our
      inability to accurately predict the development of asthma and allergy has led to
      conflicting data from recent prevention studies. Nonetheless, some useful
      recommendations can be made. Exclusive breast-feeding and avoidance of exposure
      to environmental tobacco smoke exposure can be safely recommended for the whole
      population, not only for prevention of allergy but also for other known benefits.
      Additionally, for children at high risk of allergy, maternal exclusion diet
      during lactation and protein hydrolysate as a supplement or alternative for
      children who could not be breast-fed seems to provide further protection. The
      preventive effect of avoidance of house dust mite allergen alone during pregnancy
      or after birth is disappointing. However, prospective randomized studies
      evaluating a combined food and house dust mite allergen avoidance regimen show
      some protection against atopic dermatitis in infancy and asthma in later
      childhood. Urgent research is needed to accurately identify children at high risk
      and to test novel preventative measures with the potential for immunomodulation.
      Further randomized controlled trials are also needed with long-term follow up to
      evaluate combined approaches that might provide maximum benefit.

PMID- 15990762
TI  - Effect of body mass index on natriuretic peptide levels in patients with acute
      congestive heart failure: a ProBNP Investigation of Dyspnea in the Emergency
      Department (PRIDE) substudy.
AB  - BACKGROUND: Obesity is associated with lower B-type natriuretic peptide (BNP)
      levels in healthy individuals and patients with chronic congestive heart failure
      (CHF). Neither the mechanism of natriuretic peptide suppression in the obese
      patient nor whether obesity affects natriuretic peptide levels among patients
      with acute CHF is known. METHODS: The associations of amino-terminal pro-BNP (NT
      proBNP), BNP, and body mass index (BMI) were examined in 204 subjects with acute
      CHF. Multivariable regression analyses were performed to identify factors
      independently related to NT-proBNP and BNP levels. RESULTS: Across clinical
      strata of normal (<25 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30
      kg/m2) patients, median NT-proBNP and BNP levels decreased with increasing BMI
      (both P values < .001). In multivariable analyses adjusting for covariates known
      to affect BNP levels, the inverse relationship between BMI and both NT-proBNP and
      BNP remained ( P < .05 for both). Using a cut point of 900 pg/mL, NT-proBNP was
      falsely negative in up to 10% of CHF cases in overweight patients (25-29.9 kg/m2)
      and 15% in obese patients (> or =30 kg/m2). Using the standard cut point of 100
      pg/mL, BNP testing was falsely negative in 20% of CHF cases in both overweight
      and obese patients. The assays for NT-proBNP and BNP exhibited similar overall
      sensitivity for the diagnosis of CHF. CONCLUSIONS: When adjusted for relevant
      covariates, compared with normal counterparts, overweight and obese patients with
      acute CHF have lower circulating NT-proBNP and BNP levels, suggesting a BMI
      related defect in natriuretic peptide secretion. NT-proBNP fell below the
      diagnostic cutoff for CHF less often than BNP in overweight and obese
      individuals; however, when used as a diagnostic tool to identify CHF in such
      patients, both markers may have reduced sensitivity.

PMID- 15990766
TI  - Contemporaneous maturation of immunologic and respiratory functions during early
      childhood: implications for development of asthma prevention strategies.
AB  - The term asthma refers to a spectrum of wheezing syndromes resulting from airways
      inflammation triggered by a range of environmental stimuli, the most important of
      which are aeroallergens and viruses. We describe below a model for the cause of
      atopic asthma in which discrete sets of developmental factors governing the
      postnatal maturation of the immune and respiratory systems play central and
      complementary roles in disease causality. Within the immune system, the relevant
      developmental processes involve maturation of TH1 and associated innate immune
      functions that combat infection and concomitantly antagonize the early
      programming of TH2-polarized immunologic memory against inhalant allergens.
      Within the respiratory system, the relevant developmental processes involve
      intensive lung growth and airway remodeling during infancy. We hypothesize that
      delayed maturation of TH1-associated functions during early postnatal life
      increases the risk for sensitization to aeroallergens and for severe respiratory
      infection, resulting in airway inflammation at a crucial stage in lung
      development and precipitating changes in lung growth that are the harbingers of
      susceptibility to persistent asthma. We further hypothesize that protection of
      the growing lung against the effects of inflammation during infancy and early
      childhood has unique potential as a generic strategy for asthma prophylaxis.

PMID- 15990768
TI  - Allergen avoidance in asthma: what do we do now?
AB  - Although allergen exposure can clearly aggravate the condition of sensitized
      patients with asthma, there is uncertainty and controversy about exactly which
      allergen avoidance interventions should be recommended to patients with asthma.
      Interventions that appear logical may fail to be clinically efficacious for
      several reasons. Although narrow interventions, such as allergen-impermeable
      mattress covers to reduce exposure to dust mite allergens, may offer little
      benefit if used alone, recent evidence suggests that a multifaceted, home-based
      environmental intervention focusing on multiple exposures may provide clinical
      benefits to patients with asthma. The role of allergen avoidance in infancy in
      the primary prevention of asthma is a subject of active investigation, but data
      remain too preliminary to make public health recommendations in this regard.

PMID- 15990769
TI  - New therapeutic strategy for combating the increasing burden of allergic disease:
      Probiotics-A Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota
      (NAMI) Research Group report.
AB  - The dietary approach to reducing the risk of atopic diseases in infancy is
      evolving from passive allergen avoidance to active stimulation of the immature
      immune system, the aim of which is to support the establishment of tolerance. The
      intestinal mucosa and the mucosa-associated immune system are the primary loci of
      allergen contact and induction of immune responsiveness. In this review we
      discuss cross-talk between the intestinal microbiota and the host as it pertains
      to healthy immunologic maturation. Understanding these complex phenomena provides
      the rationale for the use of probiotics in reducing the risk and nutritional
      management of atopic disease.

PMID- 15990770
TI  - Immigration to the United States and acculturation as risk factors for asthma and
      allergy.

PMID- 15990771
TI  - Associations of place of birth with asthma and wheezing in Mexican American
      children.
AB  - BACKGROUND: There are wide global variations in the prevalence of asthma and
      wheezing. OBJECTIVES: We examined the associations of place of birth with doctor
      diagnosed asthma, wheezing in the past 12 months, and other allergic conditions
      in Mexican American children. METHODS: The study used data on 4121 Mexican
      American children age 2 months to 16 years who participated in the Third National
      Health and Nutrition Examination Survey. RESULTS: The risk of asthma was
      associated with being born in the United States after adjusting for sex, age,
      history of ear infection, and having a regular place for health care (odds ratio,
      2.19; 95% CI, 1.09-4.40). Among children with no previous history of ear
      infection, US-born children were more likely to report wheezing in the past 12
      months than their peers born in Mexico after controlling for confounding
      variables (odds ratio, 2.05; 95% CI, 1.09-3.87). Mexican American children born
      in the United States were more likely to have positive skin reaction to cat,
      house mite, Alternaria alternata , peanut, Bermuda grass, and short ragweed but
      were less likely to have a positive skin test to German cockroaches after
      adjusting for sex, age, ear infection, having a regular place for health care,
      and area of residence. CONCLUSION: Our study indicated significant associations
      of place of birth with respiratory symptoms and allergic conditions in Mexican
      American children. These findings highlight the need for further studies to
      examine environmental factors that change by migration and explain the observed
      differential in the risk of asthma or wheezing.

PMID- 15990772
TI  - The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of
      age.
AB  - BACKGROUND: Avoidance of any one of the individual risk factors associated with
      childhood asthma has not been successful in preventing its development.
      OBJECTIVE: The purpose of this study is to determine the effectiveness of a
      multifaceted intervention program for the primary prevention of asthma in high
      risk infants at 7 years of age. METHODS: Five hundred forty-five high-risk
      infants with an immediate family history of asthma and allergies were
      prospectively randomized into intervention or control groups prenatally.
      Intervention measures introduced before birth and during the first year of life
      included avoidance of house dust, pets, and environmental tobacco smoke and
      encouragement of breast-feeding with delayed introduction of solid foods.
      Assessment of outcomes at 7 years consisted of examination by pediatric
      allergists, methacholine inhalation tests, and allergy skin tests. RESULTS: At 7
      years, 469 of the 545 children were contacted, and 380 returned for further
      assessment. The prevalence of pediatric allergist-diagnosed asthma was
      significantly lower in the intervention group than in the control group (14.9% vs
      23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic
      rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to
      any common allergen), and bronchial hyperresponsiveness (defined as the
      provocative concentration of methacholine that induced a 20% decrease in FEV 1
      from a postsaline value of less than 7.8 mg/mL) were not significantly different
      between the 2 groups. The prevalence of asthma (defined as wheeze without colds
      and the presence of bronchial hyperresponsiveness) was also significantly lower
      in the intervention group compared with the control group (12.9% vs 25.0%;
      adjusted risk ratio, 0.39; 95% CI, 0.22-0.71). CONCLUSION: The multifaceted
      intervention program was effective in reducing the prevalence of asthma in high
      risk children at 7 years of age.

PMID- 15990774
TI  - Allergy-related genes in microarray: an update review.
AB  - Microarrays have attracted tremendous interest among biologists. However,
      questions have been raised regarding the reproducibility between experiments
      performed in different laboratories using different platforms. Here, we discuss
      these problems and reach the following conclusions. First, the reproducibility
      between different platforms of arrays is low, but bioinformatics may permit
      compensation at least among oligonucleotide microarrays. Second, it is hard to
      interpret microarray results generated using mixed cell populations. Hierarchical
      clustering may be applied to identify whether upregulated transcripts in an
      inflammatory tissue were caused simply by an increased number of inflammatory
      cells.

PMID- 15990775
TI  - Genetic regulation of IgE responses: Achilles and the tortoise.
AB  - In the last few decades, basic biology and immunology have thrived, largely
      thanks to the use of model organisms that allow exploration of complex functions
      in ideal experimental conditions and genetically defined backgrounds. IgE
      regulation studies are no exception to this rule. The current challenge is to
      anchor what we are learning in test tubes and animals to mechanisms of disease in
      patients with allergy. With information about the human genome rapidly piling up,
      and strong associations between single nucleotide polymorphisms and disease
      phenotypes reported more and more often, it is becoming clear that such anchoring
      cannot occur without a robust integration between the biology of model systems
      and the biology of natural genetic variants. Here we will argue that an essential
      component of this integration is the functional analysis of the mechanisms
      through which natural variation affects pathways relevant to the pathogenesis of
      IgE-dependent inflammation.

PMID- 15990776
TI  - Modulation of GM-CSF release by enantiomers of beta-agonists in human airway
      smooth muscle.
AB  - BACKGROUND: beta 2 -Adrenergic receptor agonists can reduce the release of GM-CSF
      by human airway smooth muscle cells (HASMCs). These effects are considered anti
      inflammatory and are ascribed to the activity of the (R)-enantiomer within the
      racemate of the agonist. However, the effect of the (S)-enantiomer on GM-CSF
      release, once thought to be inert, has not been extensively explored. Objective
      We hypothesized that the (S)-enantiomer may counter the effects of the (R)
      enantiomer, potentially increasing GM-CSF release. Therefore, the effects of
      administration of individual and combined enantiomers on GM-CSF release were
      examined. METHODS: Cultured HASMCs were stimulated with IL-1beta, TNF-alpha, and
      IFN-gamma and treated with (R)-enantiomers and (S)-enantiomers of albuterol and
      formoterol, with and without propranolol and ICI-118,551, and in combination with
      dexamethasone. GM-CSF in the resulting conditioned media was assessed by ELISA.
      RESULTS: (R)-enantiomers significantly reduced GM-CSF release by as much as 41% (
      P < .05), which was reversible with propranolol. In contrast, (S)-enantiomers
      significantly increased GM-CSF release by as much as 34% ( P < .05) over release
      with no drug, and by 25% to 40% ( P < .05) when added with (R)-enantiomers. The
      decremental effect of dexamethasone was amplified by (R)-enantiomers but
      inhibited by (S)-enantiomers. Both propranolol and ICI-118,551 alone increased GM
      CSF release in a concentration-dependent fashion, similar to (S)-enantiomers.
      CONCLUSION: We conclude that GM-CSF release by HASMC is downregulated by (R)
      enantiomers and enhanced by (S)-enantiomers. The reversal of (R)-enantiomer and
      dexamethasone effects by the (S)-enantiomer suggests suppression of their anti
      inflammatory effects, perhaps through an antagonistic mechanism similar to
      propranolol.

PMID- 15990777
TI  - IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen
      exposure: effect of immunotherapy.
AB  - Background IL-9 is an important stimulus for tissue infiltration by mast cells, a
      feature requiring concomitant activation of c-Kit. Objectives We assessed IL-9
      expression and c-Kit + mast cells in the nasal mucosa of patients with allergic
      rhinitis during seasonal pollen exposure and observed the effects of allergen
      immunotherapy. Methods We studied 44 patients with seasonal rhinitis and asthma
      before and 2 years after a double-blind trial of grass pollen immunotherapy.
      Nasal mucosal IL-9 + cells and c-Kit + mast cells were assessed by means of
      immunochemistry. Cell types expressing IL-9 protein were determined by means of
      dual immunofluorescence. IL-9 mRNA-positive cells were assessed by means of in
      situ hybridization, and their phenotype was determined by using sequential
      immunohistochemistry and in situ hybridization. Results Nasal mucosal c-Kit +
      mast cells were increased during the pollen season ( P = .0001). IL-9 mRNA
      positive cells also tended to increase ( P = .1) and correlated with nasal EG2 +
      eosinophils ( r = 0.47, P = .05) and IL-5 mRNA-positive cells ( r = 0.54, P =
      .02). The cell sources of IL-9 included T cells, eosinophils, neutrophils, and
      mast cells. When compared with placebo, successful pollen immunotherapy markedly
      inhibited seasonal increases in nasal mucosal c-Kit + mast cells ( P = .001) and
      the seasonal expression of IL-9 mRNA-positive cells ( P = .06). Immunotherapy
      also inhibited IL-9 protein expression from nonendothelial cell sources ( P =
      .0007). Conclusion IL-9 is upregulated in the nasal mucosa during the pollen
      season and correlates with tissue infiltration by eosinophils. Successful pollen
      immunotherapy is associated with inhibition of seasonal increases in both nasal c
      Kit + mast cells and eosinophils. This effect might be explained, at least in
      part, by the reduced local expression of IL-9.

PMID- 15990778
TI  - Expression of functional cysteinyl leukotriene receptors by human basophils.
AB  - BACKGROUND: Synthesis of leukotriene (LT) C 4 by basophils and mast cells is an
      important component of IgE-mediated inflammation, resulting in increased levels
      of the cysteinyl leukotrienes (cysLTs) LTC 4 , LTD 4 , and LTE 4 . Receptors for
      cysLTs are expressed on a variety of peripheral blood leukocytes, but of
      interest, they are also expressed on cells that synthesize LTC 4 , such as
      eosinophils and mast cells. OBJECTIVE: We examined human basophils for expression
      and function of cysLT receptor type 1 (cysLT1) and cysLT receptor type 2
      (cysLT2). METHODS: Basophils were purified from human blood and analyzed by means
      of RT-PCR, Western blotting, and flow cytometry for receptor expression.
      Basophils were also examined for functional responses to LTD 4 , including
      cytosolic calcium flux, histamine release, viability, and chemotaxis. RESULTS: We
      found that basophils express mRNA for cysLT1 and cysLT2. CysLT1 and cysLT2 were
      also detectable by means of flow cytometry, but only cysLT2 was detectable by
      means of Western blotting with available antibodies. Increases in cytosolic
      calcium induced by LTD 4 -stimulated basophils were inhibited by the cysLT1
      receptor antagonist zafirlukast, confirming the presence of functional cysLT1
      receptors on basophils. There was no significant effect of LTD 4 on histamine
      release; however, LTD 4 decreased CD95 (Fas) expression on basophils in several
      day cultures. CONCLUSIONS: We have demonstrated that basophils express the cysLT
      receptors cysLT1 and cysLT2, and some functional responses to LTD 4 can be
      observed.

PMID- 15990779
TI  - Short and long-term effects of cigarette smoking independently influence exhaled
      nitric oxide concentration in asthma.
AB  - BACKGROUND: The fractional concentration of nitric oxide in exhaled breath (FeNO)
      is elevated in asthma. FeNO measurement has been proposed as a noninvasive index
      of disease activity. Cigarette smoking suppresses FeNO, which limits its use in
      smokers. OBJECTIVE: To identify and model short-term and long-term influences of
      cigarette smoking on FeNO. METHODS: The smoking history, FeNO, and fractional
      concentration of carbon monoxide in exhaled breath (FeCO) were measured in 53
      subjects with asthma and 51 control subjects. A mathematical model of the short
      term and long-term effects of cigarette smoking on FeNO was derived. RESULTS:
      Subjects with asthma had higher FeNO than controls ( P < .001). Smokers had
      increased FeCO ( P < .001). The short-term effect (hours since last cigarette)
      was associated with increased FeNO ( P < .01) and decreased FeCO ( P < .05). The
      long-term effect (years smoked) was associated with decreasing FeNO only in the
      subjects with asthma ( r = -0.62; P = .005). These short-term and long-term
      effects were independent and were combined in a model predicting FeNO, predicted
      log 10 FeNO = 1.23 - 0.58 e -0.34t - 0.00000103 x (lifetime cigarettes), where t
      = hours since the last cigarette. This gave a convincing prediction of FeNO ( r =
      0.83; P < .0001). CONCLUSION: Short-term and long-term effects of smoking
      influenced the measurement of FeNO. We defined a model that describes these
      effects. The use of this formula may improve the value of FeNO measurements in
      smokers with asthma.

PMID- 15990780
TI  - Proasthmatic effects and mechanisms of action of the dust mite allergen, Der p 1,
      in airway smooth muscle.
AB  - BACKGROUND: House dust mite allergen exposure is a key risk factor for the
      development of allergic asthma. Beyond provoking immune cell-mediated allergic
      responses, house dust mite allergens were recently shown to exert direct effects
      on airway structural cells secondary to their intrinsic protease activities.
      OBJECTIVE: This study tested the hypothesis that house dust mite allergen
      exposure can produce changes in airway responsiveness through a direct effect on
      airway smooth muscle (ASM). METHODS: Isolated rabbit ASM tissues were exposed to
      the house dust mite allergen, Der p 1, and induced changes in ASM responsiveness
      and activation of mitogen-activated protein kinase (MAPK) signaling pathways were
      examined under different experimental conditions. RESULTS: The observations
      demonstrated the following: (1) Der p 1 exposure elicited enhanced constrictor
      responses and impaired relaxation responses in the ASM tissues, (2) these
      proasthmatic-like effects of Der p 1 were attributed to its intrinsic cysteine
      protease activity, and (3) the induced changes in ASM responsiveness were
      associated with activation of both the extracellular signal-regulated kinase
      (ERK) 1/2 and the p38 MAPK signaling pathways. Additionally, specific blockade of
      ERK1/2 signaling was found to prevent the Der p 1-induced changes in ASM
      responsiveness, whereas inhibition of p38 MAPK signaling enhanced the
      proasthmatic-like action of Der p 1, with the latter effect a result of augmented
      activation of ERK1/2. CONCLUSION: These findings are the first to demonstrate
      that the dust mite allergen, Der p 1, can directly elicit changes in ASM
      responsiveness that are associated with activation of MAPK signaling, wherein
      proasthmatic effects induced by Der p 1 are attributed to activation of ERK1/2,
      whereas coactivation of p38 MAPK exerts a homeostatic action by negatively
      regulating ERK1/2 signaling.

PMID- 15990781
TI  - Timing and intensity of early fevers and the development of allergies and asthma.
AB  - BACKGROUND: Early childhood fevers appear to protect against later allergies and
      asthma. What is not known is the time in which fevers exert this effect and
      whether the degree of temperature increase is important. OBJECTIVE: We sought to
      examine the relationship between the time and degree of early fevers and later
      allergies and asthma. METHODS: Eight hundred thirty-five children from southeast
      Michigan were enrolled at birth. Clinic records from their first 2 years were
      abstracted for episodes of fever. At age 6 to 7 years, children underwent allergy
      testing. We examined fevers occurring within 6-month intervals in the first 2
      years of life and outcomes at age 6 to 7 years. The primary outcome measures were
      allergic sensitization, asthma, asthma with allergic sensitization, and asthma
      without allergic sensitization. RESULTS: In the unadjusted analysis each episode
      of fever between 7 and 12 months of age was associated with a lower odds of
      allergic sensitization (odds ratio [OR], 0.71; 95% CI, 0.54-0.93) and asthma with
      allergic sensitization (OR, 0.43; 95% CI, 0.21-0.90) at age 6 to 7 years.
      Likewise, every 1 degrees C increase in the maximum temperature between 7 and 12
      months was associated with a lower odds of allergic sensitization (OR, 0.77; 95%
      CI, 0.61-0.96) and asthma with allergic sensitization (OR, 0.62; 95% CI, 0.40
      0.94). After adjusting for potential confounders, each episode of fever between 7
      and 12 months was associated with a lower likelihood of asthma with allergic
      sensitization (adjusted OR, 0.33; 95% CI, 0.11-0.94) at age 6 to 7 years.
      CONCLUSIONS: Both the timing and intensity of childhood fevers appear to be
      important factors in the development of allergies and asthma.

PMID- 15990782
TI  - Double-blind comparative study of cluster and conventional immunotherapy
      schedules with Dermatophagoides pteronyssinus.
AB  - BACKGROUND: The conventional schedule for subcutaneous immunotherapy with
      allergen extracts, although efficacious and safe, is slow during the dose
      increase phase. OBJECTIVE: We sought to compare the efficacy and safety of
      subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized
      extract given in a 6-week cluster period and a conventional 12-week schedule
      during the incremental-dose phase. METHODS: Of 239 patients with rhinitis,
      allergic bronchial asthma, or both caused by D pteronyssinus , 120 were randomly
      assigned to the cluster schedule, and 119 were randomly assigned to the
      conventional schedule. A biologically standardized D pteronyssinus depot extract
      (ALK-Abello S.A., Madrid, Spain) was administered in a placebo-controlled, double
      blind fashion during the initial phase of cluster or conventional treatment. We
      recorded adverse reactions, clinical efficacy, cutaneous reactivity, and serum
      specific immunoglobulins to D pteronyssinus before immunotherapy, when the
      maximum dose was reached in the cluster and conventional schedules, and after 1
      year of treatment. RESULTS: The cluster schedule reduced the time to maintenance
      dose by 46% and caused systemic adverse reactions (all mild) after only 0.15% of
      injections, with no differences in comparison with the conventional schedule.
      Cluster immunotherapy led to decreases in asthma and rhinitis symptoms, reduced
      the cutaneous reactivity, and produced the increase in specific IgE and IgG 4
      levels on reaching the maintenance dose in the sixth week, 6 weeks earlier than
      with the conventional schedule. CONCLUSION: The cluster schedule for the initial
      phase of immunotherapy with incremental doses of D pteronyssinus is a safe
      alternative to conventional immunotherapy and offers the further advantage of
      achieving clinical and immunologic improvements sooner.

PMID- 15990783
TI  - Allergens and allergy prevention: where to next?

PMID- 15990784
TI  - Improving indoor environments: reducing allergen exposures.
AB  - Homes cannot be made allergen free, but exposure to the major indoor allergens
      can be reduced. All reduction recommendations are based on the principle of
      reducing or isolating the source, and certain recommendations can be made on the
      basis of published evidence. House dust mite avoidance measures include fitting
      allergen-proof mattress and pillow encasings, washing bedding regularly, and
      reducing humidity. Furred pet avoidance requires removal of the pet form the
      home, followed by thorough and repeated cleaning; room air cleaners, washing the
      pet, and isolating the pet from a bedroom are ineffective alternatives. Cockroach
      allergen avoidance begins with effective pest control, followed by thorough and
      repeated cleaning; 1 to 2 months are required to eliminate roaches, and an
      additional 4 to 6 months are required to remove residual allergen. Once allergen
      levels have been reduced, continued efforts are necessary to maintain the home
      free of allergen sources.

PMID- 15990785
TI  - Progression of self-reported symptoms in laboratory animal allergy.
AB  - BACKGROUND: Laboratory animal allergy is a common illness among workers exposed
      to laboratory animals and can progress to symptoms of asthma. OBJECTIVES: This
      study evaluates the continuum of disease from allergy symptoms to asthma symptoms
      in a dynamic cohort of workers exposed to animals in a pharmaceutical company.
      METHODS: Data arose from annual questionnaires administered to workers in a
      surveillance program established to monitor exposure to animals and the
      development of allergy. The life-table method was used to compare asthma-free
      survival between workers with and without symptoms of allergy. A Cox proportional
      hazards model was used to examine the effects of covariates on the development of
      asthma. RESULTS: A total of 603 workers contributed 2527.4 person-years to the
      study over the 12.3-year period. The probabilities of experiencing asthma
      symptoms by the 11th year of follow-up were 0.367 for workers with allergy
      symptoms and 0.052 for those without allergy symptoms. The hazard ratio for
      asthma symptoms when comparing workers with and without allergy symptoms was 7.39
      (95% CI, 3.29-16.60) after adjustment for sex and family history of allergy.
      Female subjects developed asthma at a rate 3.4 times that of male subjects.
      CONCLUSIONS: This study supports the hypothesis that laboratory animal allergy
      symptoms are a major risk factor for the development of asthma. It also suggests
      a heightened risk of asthma for women who work with laboratory animals, a finding
      that has not been previously reported.

PMID- 15990786
TI  - Exposure to indoor allergens in day-care facilities: results from 2 North
      Carolina counties.
AB  - BACKGROUND: With 63% of US children under 5 years of age in regular child care,
      day-care facilities could be an important source of exposure to indoor allergens.
      OBJECTIVE: This study examined levels of 7 indoor allergens in 89 day-care
      facilities in 2 North Carolina counties. METHODS: At each facility, a
      questionnaire was administered, observations were made, and vacuumed dust samples
      were collected from carpeted and noncarpeted areas of one room. Allergen
      concentrations were measured with antibody-based ELISAs. RESULTS: Each allergen
      was detected in a majority of facilities (52% to 100%). Geometric mean
      concentrations were 5.19 mug/g for Alternaria alternata , 2.06 mug/g for Can f 1,
      1.43 microg/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 microg/g for Der p 1, 0.10
      microg/g for Der f 1, and 0.01 microg/g for Mus m 1. Concentrations for 5 of the
      7 allergens were not statistically different from concentrations found in
      southern US homes sampled in the National Survey of Lead and Allergens in
      Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata ,
      Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet.
      CONCLUSIONS: In this survey of day-care facilities in North Carolina, detectable
      levels of indoor allergens were commonly found. For many young children and day
      care staff, day-care facilities might be a source of clinically relevant
      exposures to indoor allergens.

PMID- 15990787
TI  - Cockroach allergen Bla g 2: an unusual aspartic proteinase.
AB  - BACKGROUND: Enzymatic activity of mite, fungal, and bee venom allergens is
      thought to potentiate their allergenicity. Bla g 2 is a potent cockroach
      allergen, but despite sharing sequence homology with aspartic proteinases, it
      contains critical amino acid substitutions that impair proteolytic activity. The
      biologic function of Bla g 2 remains unclear. OBJECTIVE: We sought to investigate
      the effects of specific amino acid substitutions on enzymatic activity, and the
      peptide-binding capability of Bla g 2. METHODS: Site-directed mutagenesis was
      used to produce a recombinant Bla g 2 mutant (Mut) with corrected canonical
      triads and a flap region. Another mutant (MutF - ) was expressed after additional
      mutations in the flap region of Mut. Bla g 2 wild-type (Wt), Mut, and MutF - were
      assayed for aspartic proteinase activity, and Bla g 2 Wt was tested for pepstatin
      binding. RESULTS: Recombinant Bla g 2 Wt and Mut did not show enzymatic activity
      in a milk-clotting and hemoglobin assay. By using a modified hemoglobin assay,
      residual activity inhibited by pepstatin was detected for MutF - and Wt at 20
      microg/mL, whereas pepsin was active at a 1000-fold lower concentration. Most of
      Bla g 2 binding to pepstatin-agarose was nonspecific. CONCLUSION: Residual
      proteolytic activity was found for Bla g 2 at concentrations of approximately 4
      mM. This weak activity suggests that proteolysis is not the primary function of
      this allergen and that it is unlikely to contribute to the allergenicity of Bla g
      2. Bla g 2 has a cleft that might specifically bind ligands other than pepstatin.

PMID- 15990788
TI  - Allergen sensitization evaluation and allergen avoidance education in an inner
      city adult cohort with persistent asthma.
AB  - BACKGROUND: Asthma morbidity, mortality, and health services utilization are
      highest among inner-city populations. The National Asthma Education and
      Prevention Program Expert Panel recommends that all patients with moderate and
      severe persistent asthma be evaluated for sensitization to environmental
      allergens. OBJECTIVE: This study examined whether a cohort of inner-city adults
      hospitalized with asthma had been evaluated for allergen sensitization, received
      avoidance counseling, and followed through on these recommendations. METHODS: One
      hundred sixty-nine eligible patients who were part of a prospective cohort of all
      adults hospitalized in an inner-city hospital over a consecutive 12-month period
      completed a questionnaire to assess allergen sensitization evaluation, avoidance
      education, and adherence. RESULTS: Overall, 60% of patients had ever been
      evaluated for allergen sensitization. Among those who were evaluated, 94.0% were
      sensitized to at least one antigen: 91.5% to dust mites, 90.5% to outdoor
      allergens, 77.9% to cats, 69.5% to dogs, 68.4% to molds, and 61% to cockroaches.
      Approximately half of the patients sensitized to dust mite (55.1%) or mold
      (52.8%) were given any avoidance-abatement advice. Patient adherence to this
      advice was highly variable. Allergen sensitization evaluation was more likely
      among women (odds ratio, 3.05; CI, 1.64-8.64) and those who use oral steroids
      most or all of the time (odds ratio, 7.14; CI, 2.25-22.56) and less likely among
      smokers (odds ratio, 0.26; CI, 0.11-0.61). CONCLUSION: In this population of
      inner-city adults hospitalized with asthma, the quality of allergen sensitization
      evaluation, avoidance education, and patient adherence with these recommendations
      was suboptimal.

PMID- 15990789
TI  - Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to
      foods, drugs, and insects.
AB  - This review highlights some of the research advances in allergic skin disease,
      anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects that
      were reported primarily in the Journal in 2004. Clinical observations included
      that gastrointestinal symptoms during anaphylaxis are associated with an
      increased risk for hypotension; recurrence of peanut allergy can occur for about
      8% of children who pass an oral food challenge and is associated with continued
      avoidance of the food after the challenge; seafood allergy is reported by 2.3% of
      the US population; and determination of the time to resolution of childhood egg
      and milk allergy might be predictable by means of serial determination of food
      specific IgE levels. The comorbid effects of atopic dermatitis (AD) on asthma and
      the role of topical calcineurin inhibitors in the therapy of AD were also
      addressed. Basic and translational research observations indicate that improved
      diagnosis and therapy might become possible on the basis of reported
      identification or characterization of allergens such as: lipid transfer proteins
      and birch pollen-related cross-reactive allergens in plant foods; proteins in
      scorpion venom that cross-react with proteins from imported fire ant; mosquito
      saliva proteins responsible for systemic anaphylaxis; and IgE binding to
      quinolones detectable with an in vitro immunoassay. In addition, advances in
      understanding immune regulation associated with abrogation of oral tolerance in
      food allergy and of dendritic cell function, modulation of regulatory T cells,
      and chemokine expression in AD have elucidated possible targets for future
      intervention.

PMID- 15990790
TI  - Parental use of EpiPen for children with food allergies.
AB  - BACKGROUND: EpiPen is often underused in children with food allergy experiencing
      anaphylaxis. OBJECTIVE: We explored whether underuse of EpiPen might be
      attributed to parental discomfort with administration, as measured by a lack of
      parental empowerment and knowledge of proper administration. METHODS: A written
      survey was mailed to parents of children with food allergy. Those children with
      physician-diagnosed food allergy who had been prescribed EpiPen were included in
      the analysis. Parents were recruited from a local food-allergy support group and
      private allergy practice. Perceived comfort with administering EpiPen was
      measured by using a 10-cm visual analog scale. Knowledge of EpiPen use and
      anaphylaxis was tested by using a series of multiple-choice questions.
      Empowerment was measured with a 16-item instrument that included statements from
      the Family Empowerment Scale. Multiple regression analysis was used to determine
      how much of the variance in the comfort ratings could be explained by knowledge,
      empowerment, and other factors assessed in the survey. RESULTS: Of 360 mailed
      surveys, 165 (46%) completed surveys met the inclusion criteria and were
      analyzed. Anaphylaxis was reported in 42% of children (n = 70); 8% of parents (n
      = 14) had administered EpiPen to their child. Factors correlating with comfort
      included prior administration of EpiPen ( P = .009), EpiPen training ( P = .005),
      and empowerment ( P < .0005). Neither a history of anaphylaxis nor knowledge
      correlated with an increased level of comfort with administration. CONCLUSIONS:
      Empowerment directly correlated with increased comfort with EpiPen use, but
      knowledge did not. Physicians should continue to instruct all parents on EpiPen
      administration because this correlated significantly with comfort. Other
      psychological factors beyond empowerment might contribute to underuse of EpiPen.

PMID- 15990791
TI  - Cystatin A inhibits IL-8 production by keratinocytes stimulated with Der p 1 and
      Der f 1: biochemical skin barrier against mite cysteine proteases.
AB  - BACKGROUND: Der p 1 and Der f 1 are the most immunodominant allergens produced by
      house dust mites and are suspected to be involved in the pathogenesis of allergy
      through their cysteine protease activity. However, stimulation of keratinocytes
      by these protease allergens and protective systems in the skin against them have
      not been well investigated. OBJECTIVE: We purified and identified the dominant
      skin-derived inhibitor against the proteolytic activities of these allergens and
      analyzed its effect on keratinocyte activation. METHODS: Recombinant allergens
      were used for the experiments. We analyzed whether human sweat inhibits the
      enzymatic activities of Der p 1 and Der f 1 and used sweat as the skin-derived
      material to isolate the inhibitor. The inhibitor was purified by means of column
      chromatography and subsequently identified by means of protein sequencing and
      immunoblotting. Keratinocytes were stimulated with the allergens in the absence
      or presence of the inhibitor, and the concentration of secreted IL-8 was
      measured. RESULTS: Sweat inhibited the proteolytic activities of Der p 1 and Der
      f 1. The sweat inhibitor was identified as cystatin A. The stimulation of normal
      human keratinocytes and the human keratinocyte cell line HaCaT with these
      protease allergens upregulated IL-8 secretion, and addition of cystatin A blocked
      this upregulation. Normal human keratinocytes secreted cystatin A into the
      medium. CONCLUSIONS: The proteolytic activity of Der p 1 and Der f 1 stimulates
      human keratinocytes in vitro. Cystatin A produced by keratinocytes is the
      dominant biochemical skin barrier that eliminates the enzymatic activity of these
      mite cysteine proteases and prevents them from stimulating keratinocytes.

PMID- 15990792
TI  - Association of NOD1 polymorphisms with atopic eczema and related phenotypes.
AB  - BACKGROUND: Interactions with microbial pathogens are crucial for the maturation
      of the immune system. The nucleotide-binding oligomerization domain protein 1
      (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram
      negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a
      region that has been linked with atopy. Recently, polymorphisms of the closely
      related NOD2 have been associated with atopy-related traits. OBJECTIVES: Within a
      large population-based cohort of German adults (n = 1417), a case-control
      population for atopic eczema (n = 454), and a large cohort of parent-offspring
      trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for
      associations with atopic phenotypes. Methods Subjects were phenotyped by
      standardized questionnaires and interviews, skin examination, and serum IgE
      measurements. Genotyping was performed by using matrix-assisted laser desorption
      ionization-time of flight mass spectrometry. RESULTS: Analyses revealed
      significant association of one NOD1 haplotype with atopic eczema in the
      population-based cohort ( P = .004) and the case-control population ( P = .003).
      Another NOD1 haplotype was associated with decreased total IgE ( P = .008). In
      addition, significant associations with total serum IgE levels were observed for
      polymorphisms rs2907748 ( P = .006), rs2907749 ( P = .012), and rs2075822 ( P =
      .018). These polymorphisms were significantly associated with atopic eczema and
      asthma in the family-based association analyses ( P = .001-.043). Seven
      polymorphisms showed significant transmission distortion for total IgE levels ( P
      values < .0001-.029). CONCLUSION: These data indicate that genetic variants
      within NOD1 are important determinants of atopy susceptibility.

PMID- 15990794
TI  - CD11b-mediated migratory property of peripheral blood B cells.
AB  - BACKGROUND: CD11b belongs to the integrin family and is expressed on neutrophils,
      monocytes, natural killer cells, and a subset of lymphocytes. Although CD11b
      expressed on neutrophils and monocytes has been extensively investigated and has
      been reported to play an important role in the migration of these subsets of
      leukocytes, the function of CD11b expressed on a subset of B cells has not yet
      been clarified. OBJECTIVE: To elucidate the functional activity of CD11b
      expressed on B cells, we characterized the CD11b-expressing cells among the B
      cell population and investigated their migratory ability. METHODS: Isolated
      peripheral blood CD19 + B cells were analyzed by flow cytometry. The migratory
      ability of B cells was evaluated by the transwell assay, and the contribution of
      CD11b to this ability was investigated by using an anti-CD11b blocking mAb.
      RESULTS: The majority of CD27 - IgD + naive B cells were CD11b - , whereas most
      CD27 + memory cells were CD11b +. Among the CD27 + memory cells, expression of
      CD11b was stronger on the IgD - cells than on the IgD + cells. In the transwell
      assay, the migrating cells were predominantly CD27 + IgD - cells, most of which
      expressed CD11b. The addition of an anti-CD11b blocking mAb resulted in the
      significant reduction of the number of migrating B cells. CONCLUSION: Memory B
      cells express CD11b and, in contrast with naive B cells, have high migratory
      ability. CD11b plays an essential role in the homing process of memory cells.

PMID- 15990793
TI  - House dust extracts elicit Toll-like receptor-dependent dendritic cell responses.
AB  - BACKGROUND: Laboratory and epidemiological studies have provided indirect but
      compelling evidence that Toll-like receptors (TLRs) play an important role in
      innate host responsiveness to ambient immunostimulatory factors. However, little
      direct evidence exists. OBJECTIVE: To determine whether house dust extracts
      activate dendritic cells by TLR-dependent mechanisms. METHODS: In initial
      studies, bone marrow-derived dendritic cells were cultured with sterile house
      dust extracts, and cytokine production and costimulatory molecule expression were
      evaluated. In additional experiments, the TLR dependence of these responses was
      assessed. RESULTS: House dust extract-activated bone marrow-derived dendritic
      cells were found to produce IL-6 and IL-12 in a concentration-dependent manner
      and to increase their expression of CD40, CD80, CD86, and MHC class II molecules.
      Furthermore, correlations were seen between the relative bioactivities of house
      dust extracts and their endotoxin levels. Finally, bone marrow-derived dendritic
      cells from TLR (2, 4, and 9)-deficient mice all demonstrated attenuated
      responses, and MyD88 deficient bone marrow-derived dendritic cells were almost
      completely nonresponsive to house dust extracts. CONCLUSION: These investigations
      provide direct evidence that TLR signaling pathways play a central role in at
      least a subset of dendritic cell responses to noninfectious factors ubiquitous in
      living environments.

PMID- 15990795
TI  - Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed
      dendritic cells from allergic patients.
AB  - BACKGROUND: Lactic acid bacteria (LAB) are suggested to play a regulatory role in
      the development of allergic reactions. However, their potential effects on
      dendritic cells (DCs) directing the immune polarization remain unclear.
      OBJECTIVE: The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on
      monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust
      mite was evaluated. METHODS: MD-DCs were stimulated for 24 hours with the related
      allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were
      assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL
      10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or
      memory T cells was evaluated by determining the T-cell cytokine profile. RESULTS:
      LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1.
      Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher
      amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL
      5) production observed when naive or memory autologous T cells were cocultured
      with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally,
      in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T
      cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2
      cytokines in response to a new stimulation with Der p 1-pulsed DCs. CONCLUSION:
      Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate
      the T-cell response toward a beneficial T H 1 profile.

PMID- 15990796
TI  - Differential effects of IFN-alpha on the expression of various TH2 cytokines in
      human CD4+ T cells.
AB  - BACKGROUND: In both human subjects and mice, T helper cells are classified into 2
      subsets, TH1 and TH2 cells, on the basis of the cytokines they produce. Although
      IFN-alpha has been shown to enhance human TH1 responses, its influences on human
      TH2 responses have not yet been fully characterized. In addition, the mechanism
      for induction of TH1 responses by IFN-alpha has not been fully delineated.
      OBJECTIVE: The present study was undertaken to explore the direct effects of IFN
      alpha on the expression of various cytokines in human CD4+ T cells with a system
      using immobilized anti-CD3, which permits activation of CD4+ T cells in the
      complete absence of accessory cells. METHODS: Highly purified CD4+ T cells
      obtained from healthy donors were stimulated with immobilized anti-CD3 with or
      without IFN-alpha and IL-12 in the complete absence of accessory cells. The
      production of cytokines was estimated by means of ELISA. The expression of mRNA
      for various cytokines, as well as transcription factors, was evaluated by using
      quantitative PCR. RESULTS: IFN-alpha enhanced IL-4 protein and mRNA expression in
      immobilized anti-CD3-stimulated CD4+ T cells, irrespective of the presence of IL
      12, whereas IFN-alpha suppressed the expression of IL-5 and IL-13. Of note, IFN
      alpha enhanced the expression of mRNA for c-Maf, T-bet, and Fox-P3, irrespective
      of the presence of IL-12, but not that for GATA-3, in anti-CD3-stimulated CD4+ T
      cells. CONCLUSION: These results indicate that IFN-alpha enhances the induction
      of TH1 responses through upregulation of T-bet mRNA expression, as well as the
      induction of TH2 responses through upregulation of c-Maf mRNA expression,
      followed by IL-4 expression. Moreover, the data also suggest that IFN-alpha might
      suppress the expression of IL-5 and IL-13 in differentiated TH2 cells.

PMID- 15990797
TI  - Bet v 1142-156 is the dominant T-cell epitope of the major birch pollen allergen
      and important for cross-reactivity with Bet v 1-related food allergens.
AB  - BACKGROUND: Individuals with birch pollen allergy frequently experience
      hypersensitivity reactions to certain foods, primarily because of IgE antibodies
      specific for the major birch pollen allergen Bet v 1 that cross-react with
      homologous food allergens. OBJECTIVE: We sought to characterize the major T-cell
      epitopes of Bet v 1 and to investigate their involvement in the cellular cross
      reactivity with homologous food allergens. METHODS: T-cell epitope mapping of Bet
      v 1 was performed by testing Bet v 1-specific T-cell lines derived from 57
      individuals with birch pollen allergy, with overlapping peptides representing the
      entire allergen. T-cell lines and T-cell clones were stimulated with Bet v 1
      related major allergens from apple (Mal d 1), cherry (Pru av 1), hazelnut (Cor a
      1), celery (Api g 1), carrot (Dau c 1), and soybean (Gly m 4) and with peptides
      deduced from the C-terminal amino acid sequences of these molecules. Results Bet
      v 1 142-156 , positioned in the highly conserved C-terminal region of Bet v 1,
      was identified as the major T-cell epitope recognized by 61% of individuals. Most
      T lymphocytes specific for Bet v 1 142-156 were activated by one or more
      homologous food proteins or the respective peptides, as indicated by
      proliferation and cytokine production. CONCLUSION: The major T-cell epitope of
      Bet v 1, Bet v 1 142-156 , plays an important role in the cellular cross
      reactivity between this respiratory allergen and related food allergens. Thus T
      lymphocytes specific for Bet v 1 142-156 might be activated by various Bet v 1
      related food allergens in vivo, even out of the pollen season.

PMID- 15990798
TI  - Lack of association of the G protein-coupled receptor for asthma susceptibility
      gene with atopic dermatitis.

PMID- 15990799
TI  - Association of COX-2 gene haplotypes with prostaglandins production in bronchial
      asthma.

PMID- 15990800
TI  - Childhood cat exposure-related tolerance is associated with IL1A and IL10
      polymorphisms.

PMID- 15990801
TI  - Rapid intravenous cephalosporin desensitization.

PMID- 15990802
TI  - Expression of Fc(epsilon)RI on dendritic cell subsets in peripheral blood of
      patients with atopic dermatitis and allergic asthma.

PMID- 15990803
TI  - Response to Wolf [corrected] and Marks.

PMID- 15990804
TI  - Effects of montelukast in patients with persistent asthma using inhaled
      corticosteroids plus additional second-line therapy.

PMID- 15990805
TI  - Atopy and asthma: an epidemic of unknown cause.

PMID- 15990807
TI  - Local isotype switching to IgE in airway mucosa.

PMID- 15990812
TI  - ASGE guideline: the role of ERCP in diseases of the biliary tract and the
      pancreas.

PMID- 15990813
TI  - The changing landscape of practice patterns regarding unsedated endoscopy and
      propofol use: a national Web survey.
AB  - BACKGROUND: Lower reimbursements for endoscopic procedures and increasing demand
      for screening endoscopy over the past decade have spurred efforts to increase
      efficiency in the performance of endoscopic procedures. Two dichotomous
      approaches have emerged: (1) unsedated endoscopy and (2) propofol sedation. The
      aim was to determine national practice patterns of unsedated endoscopy and
      propofol sedation, and to assess endoscopists' attitudes toward unsedated
      screening with an electronic survey. METHODS: A short survey was developed and
      then was converted to a Web-based format. All national members of the American
      Society for Gastrointestinal Endoscopy (ASGE) were invited via electronic mail (e
      mail) to participate. Survey data were collected electronically. RESULTS: Two e
      mails elicited responses to the Web survey from 18% (724) of national ASGE
      members contacted, within 2 weeks. Of the respondents, 45% do not routinely offer
      unsedated EGD and colonoscopy, and only 15% of those respondents plan to
      incorporate unsedated endoscopy into their practice in the next year. Of the 55%
      who currently perform unsedated endoscopy, 85% do no more than 25 unsedated
      procedures per year. Lack of patient acceptance was the most common reason cited
      for not offering unsedated endoscopy. Most endoscopists felt that the
      availability of unsedated esophagoscopy or colonoscopy would not significantly
      increase screening for Barrett's esophagus or colonic polyps/colorectal cancer,
      respectively. Routine use of propofol sedation for EGD, colonoscopy, and ERCP/EUS
      was reported by 19%, 22%, and 19%, respectively. Community practitioners were
      more likely to use propofol than those at academic centers (p < 0.0002 for all).
      Of those not currently using propofol, 43% plan to incorporate it into their
      practice within the next year. Over 70% of respondents would themselves choose to
      be sedated for routine endoscopic procedures. CONCLUSIONS: Electronic surveys
      allow for rapid distribution and data collection but suffer from a limited
      response rate. The survey suggests that unsedated endoscopy has limited
      acceptance in the United States, and, without a major intervention that affects
      endoscopists' attitudes, its use is not likely to increase significantly.
      Unsedated endoscopy will not have a great impact on endoscopic screening. In
      contrast, propofol sedation has already gained acceptance in the community, and
      the routine use of propofol in endoscopy units will likely increase in the
      future.

PMID- 15990814
TI  - EUS followed by EMR for staging of high-grade dysplasia and early cancer in
      Barrett's esophagus.
AB  - BACKGROUND: Accurate staging of high-grade dysplasia and of early cancer in
      Barrett's esophagus is important in the selection of patients for endoscopic
      therapy. METHODS: Patients with Barrett's esophagus and biopsy specimen proven
      high-grade dysplasia and adenocarcinoma in focal nodular lesions or in
      endoscopically unapparent flat lesions in short-segment Barrett's esophagus were
      initially staged with EUS. In patients with disease limited to the mucosa on EUS,
      cap-assisted EMR was performed. The depth of tumor invasion on EMR specimens was
      classified in a similar manner to squamous-cell cancer of the esophagus: m1
      (epithelial layer, dysplasia), m2 (lamina propria invasion), m3 (muscularis
      mucosae invasion), sm (submucosal invasion). RESULTS: EUS was performed in 48
      consecutive patients (27 with focal nodular lesions and 21 with microscopic
      lesions), and submucosal invasion was diagnosed in 8 (confirmed in 7/8 at
      surgery). EMR was carried out in the remaining 40 patients without significant
      complications. In the 25 patients with high-grade dysplasia on prior biopsy
      specimens, EMR confirmed m1 disease in 19; whereas in 6 (24%), invasive
      adenocarcinoma was detected (to m2 in 4; to m3 in 2). In the 15 patients with
      invasive cancer on prior biopsy specimens and staged as intramucosal cancer on
      EUS, intramucosal carcinoma was confirmed in 9 (m2 in 3; m3 in 6); whereas, in 6
      patients (40%), submucosal invasion was found. Overall, EUS provided accurate
      staging in 41/48 patients (85%) with one patient overstaged and 6 patients
      understaged compared with pathologic staging obtained by surgery or EMR. Of the
      34 patients with m1 to m3 staging after EMR, 29 were treated endoscopically and
      had no evidence of cancer after a mean follow-up of 22.9 months(standard
      deviation 9.2 months). CONCLUSIONS: EMR provides pathologic staging information
      that, in addition, may be helpful after EUS if a stage-determined approach is
      used in the management of high-grade dysplasia and of early cancer in Barrett's
      esophagus. EMR may be particularly useful for staging of focal nodules or in
      short-segment Barrett's esophagus with microscopic lesions when endoscopic
      therapy is an option.

PMID- 15990815
TI  - Long-term results of photodynamic therapy with 5-aminolevulinic acid for
      superficial Barrett's cancer and high-grade intraepithelial neoplasia.
AB  - BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has
      proven to be safe and effective in patients with early neoplasia in Barrett's
      esophagus. However, long-term results in patients with high-grade intraepithelial
      neoplasia (HGIN) or with early cancer are still lacking. METHODS: The aim of the
      study was to evaluate the efficacy of ALA-PDT and the survival of patients with
      early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin
      IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6
      hours before PDT) was used as the photosensitizer. Acid suppression was
      maintained in all patients. RESULTS: Between September 1996 and September 2002,
      667 patients with early neoplasia in Barrett's esophagus were referred for local
      endoscopic therapy. A total of 558 patients fulfilled the criteria for local
      endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2]
      years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31)
      were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the
      35 patients in group A (97%) and all patients in group B (100%) achieved a
      complete response during a median follow-up period of 37 months (interquartile
      range 23-55) (not significant). One local recurrence was observed in group A and
      10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths
      were not tumor related. No major complications were observed. Disease-free
      survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it
      was 68%. The calculated 5-year survival was 97% in group A and 80% in group B,
      but there occurred no death related to Barrett's neoplasia. CONCLUSIONS: The
      excellent long-term results of PDT with ALA in patients with HGIN or mucosal
      cancer might offer PDT with ALA as an alternative to surgical esophagectomy and
      endoscopic resection, especially in cases with multifocal Barrett's neoplasia.

PMID- 15990816
TI  - Photodynamic therapy as salvage treatment for local failures after definitive
      chemoradiotherapy for esophageal cancer.
AB  - BACKGROUND: Although definitive chemoradiotherapy for esophageal cancer shows a
      high response rate, persistent or recurrent locoregional disease remains a major
      problem. Salvage esophagectomy is the only curative intent treatment option;
      however, it carries higher morbidity and mortality rates than primary
      esophagectomy. Response to second-line chemotherapy is quite dismal. METHODS:
      From December 2002 to November 2003, we applied salvage photodynamic therapy to
      13 patients with local failures after completion of chemoradiotherapy, 4 patients
      had local recurrence after achieving a complete response, and 9 had a persistent
      tumor after chemoradiotherapy. The decision to treat was based on patients'
      refusal of salvage surgery or chemotherapy. After the intravenous administration
      of 2 mg/kg of Photofrin, photoradiation treatment with an excimer dye laser was
      performed for 48 hours and 72 hours after the injection. Written informed consent
      was obtained from all patients. RESULTS: Eight patients (62%) achieved a complete
      response. After a median follow-up period of 12 months after photodynamic
      therapy, 6 patients were still free of disease, and the overall survival rate at
      1 year was 68.4%. There were no treatment-related deaths. CONCLUSIONS: Our
      results show that salvage photodynamic therapy could be a promising curative
      intent treatment option with low morbidity and mortality rates.

PMID- 15990818
TI  - Endoscopic suturing devices for treatment of GERD: too little, too late?

PMID- 15990817
TI  - Endoluminal therapy of GERD with a new endoscopic suturing device.
AB  - BACKGROUND: Endoscopic, endoluminal therapy might be an alternative treatment
      option in light of the costs of proton pump inhibitor therapy and possible
      complications after laparoscopic surgery. The aim of the current study was to
      assess the efficacy and the safety of a new endoluminal suture device (ESD) in
      pig models and humans. Secondly, 3 and 6 months' follow-ups were performed, and
      possible complications and their management were evaluated. METHODS: In the
      preclinical phase of the study, suturing procedures were practiced and evaluated
      in 8 pig models (Erlanger Endo Trainer). In the clinical phase, 20 patients with
      mild esophagitis, small or no hiatal hernia, and signs of abnormal acid exposure
      (pH measurements) were enrolled. Therapeutic endoscopy (propofol sedation) was
      performed with the flexible suture and the Ti-Knot devices, which were introduced
      over an external accessory channel, fixed on the endoscope. One to 3 sutures were
      applied per patient at the gastroesophageal junction. A 3 months' follow-up
      included upper endoscopy, manometry, 24-hour pH study, and clinical
      questionnaires. RESULTS: Visibility with the new device was good, and, in all
      cases, sutures could be applied with only minor complications. In the animal
      model, the stitches reached the muscularis propria. However, the 3-month follow
      up showed that only 12% of all plications persisted over this short period in
      humans. In addition, the clinical response was poor (no significant changes after
      the procedure: pH study, proton pump inhibitor intake, lower-esophageal sphincter
      pressure on manometry). In two patients, acute bleeding occurred, which was
      successfully controlled with endoscopic therapy. However, these patients were
      observed overnight in the hospital without further complications. The study was
      interrupted after 3 months because of the results of the interim analysis.
      CONCLUSIONS: The new endoscopic suturing device allows a feasible and safe
      technique for application of endoscopic sutures. The procedure could be performed
      on an outpatient basis by using sedation with propofol. However, the clinical
      outcome was very limited because of the high number of lost or failed plications.
      Thus, the ESD currently cannot be recommended in the treatment of patients with
      GERD.

PMID- 15990819
TI  - The clinical meaning of a nonstructural pattern in early gastric cancer on
      magnifying endoscopy.
AB  - BACKGROUND: In the field of colorectal cancer, the presence of a nonstructural
      pattern in magnifying colonoscopy means that cancer involves the submucosal
      layer. Since en bloc EMR was developed, differentiation between mucosal and
      submucosal cancer is a critical issue in the management of gastric cancer. In
      this study, we evaluated the clinical meaning of a nonstructural pattern in
      magnifying gastroscopy. METHODS: Between April 2002 and July 2003, 59 patients
      with 50 cancers and 11 adenomas were enrolled in this study. A cancerous lesion
      was subclassified into a differentiated-type group or a undifferentiated-type
      group according to histologic type. Before treatment, magnifying endoscopic
      observation was performed. After EMR or surgical intervention, resected specimens
      were observed by using stereomicroscopy. In both in vivo magnifying endoscopic
      and in vitro stereomicroscopic observations, the presence of a nonstructural
      pattern on the lesion was investigated. Compared with histologic findings, the
      clinical meaning of the presence of a nonstructural pattern on the gastric
      neoplastic lesion was evaluated. RESULTS: A nonstructural pattern could not be
      confirmed in any adenomas and in 29 of 31 mucosal differentiated cancers.
      However, in 9 of 11 submucosal cancers, a nonstructural pattern could be
      identified. CONCLUSIONS: The presence of a nonstructural pattern appeared to be a
      useful marker to not proceed with EMR of gastric cancer.

PMID- 15990820
TI  - The value of wireless capsule endoscopy in patients with complicated celiac
      disease.
AB  - BACKGROUND: Celiac disease may be complicated by symptoms that raise the
      suspicion of small-intestinal malignancy. The objective is to evaluate wireless
      capsule endoscopy (WCE) in complicated celiac disease. METHODS: This is a
      prospective study at a university referral center. There were 47 patients. The
      indications for WCE were abdominal pain (57%), cancer surveillance (23%), blood
      in the stool, or persistent iron deficiency (19%). RESULTS: Findings were
      consistent with celiac disease in 87%: atrophy (68%), fissuring (62%), and mosaic
      pattern (19%), extending to the ileum in 34%. Unexpected findings were ulceration
      in 45% (n = 21), cancer (1), polyps (1), stricture (1), submucosal mass (1),
      ulcerated nodular mucosa (2), and intussusception (1) were seen in 60%.
      CONCLUSIONS: WCE has a high yield in complicated celiac disease, by identifying
      mucosal abnormalities and by excluding adenocarcinoma.

PMID- 15990821
TI  - Double-balloon enteroscopy (push-and-pull enteroscopy) of the small bowel:
      feasibility and diagnostic and therapeutic yield in patients with suspected small
      bowel disease.
AB  - BACKGROUND: Double-balloon enteroscopy (push-and-pull enteroscopy) is a new
      method that allows complete visualization, biopsy, and treatment in the small
      bowel. This study evaluated the feasibility and the diagnostic and the
      therapeutic yield of double-balloon enteroscopy (push-and-pull enteroscopy) in
      comparison with current imaging methods. METHODS: Between March 2003 and November
      2004, 248 consecutive double-balloon enteroscopies (push-and-pull enteroscopies)
      were performed in a prospective study in 137 patients with suspected small-bowel
      disease (60 women, 77 men; mean age 56.6 +/- 17.8 years), most with chronic GI
      bleeding (66%). The examinations were carried out after negative evaluations with
      other methods or to allow biopsy or treatment in patients with known small-bowel
      findings. RESULTS: There were no relevant technical problems or severe
      complications. On average, 240 +/- 100 cm of the small bowel was visualized by
      using the oral route and 140 +/- 90 cm was visualized by using the anal route.
      The investigation time averaged 73.5 +/- 25 minutes. The overall diagnostic yield
      was 80% (109/137 patients). The main diagnosis was angiodysplasia (40/109; 37%);
      erosions and ulcerations of various etiologies were found in 27% (29/109). Polyps
      and tumors were identified, including malignancy, in 25% (27/109). Other findings
      were detected in a further 11%. No relevant pathology was found in 20%.
      Subsequent treatment was influenced by the results in 104 patients (76%):
      endoscopic therapy in 57 (41.5%), medical treatment in 23 (17%), and surgery in
      24 (17.5%). CONCLUSIONS: Double-balloon enteroscopy (push-and-pull enteroscopy)
      is safe and easily conducted. Visualization and tissue sampling are possible in
      the entire small bowel by using the oral and anal approaches, and treatment is
      possible in the same way as in standard endoscopy, avoiding open surgery. If
      further prospective studies confirm its value, double-balloon enteroscopy (push
      and-pull enteroscopy) may become a standard method of diagnostic and therapeutic
      endoscopy in the small bowel.

PMID- 15990822
TI  - Double-balloon enteroscopy: the new gold standard for small-bowel imaging?

PMID- 15990823
TI  - EUS-guided Trucut biopsy of suspected nonfocal chronic pancreatitis.
AB  - BACKGROUND: The diagnosis of early chronic pancreatitis (CP) is difficult, and
      the role of EUS-FNA cytology for this indication remains unclear. The aim of this
      study is to determine the utility and the safety profile of EUS-guided Trucut
      biopsy (EUS-TCB) for the histologic diagnosis of suspected nonfocal CP. METHODS:
      After radial EUS, patients with suspected CP (> or =3 EUS criteria) underwent
      attempted transgastric EUS-TCB of the pancreas. Histopathologic specimens were
      examined by one pathologist and were classified as nondiagnostic, normal
      pancreas, and probable or definite CP. Within 1 week after EUS, ERCP was
      performed by an endoscopist blinded to the EUS results. The severity of CP by
      ERCP was stratified by the Cambridge classification. Agreement between tests for
      the diagnosis of CP was evaluated by a kappa statistic. RESULTS: Of 45 patients
      screened, 15 declined and 30 (12 men and 18 women, mean age 44 years) underwent
      diagnostic EUS. Of these, 18 (60%) had suspected CP and 16 underwent attempted
      biopsy. Calcific pancreatitis in two patients precluded EUS-TCB. EUS-TCB results
      were as follows: probable CP (1), normal pancreas (8), nondiagnostic (6), device
      malfunction (1). Complications after EUS-TCB occurred in two patients with normal
      pancreatic biopsies were the following: acute pancreatitis (1) and abdominal pain
      without pancreatitis (1), both of whom were hospitalized and discharged within 23
      hours. Six patients refused ERCP and two (per protocol) did not undergo ERCP. For
      the remaining 22, agreement between diagnostic EUS and ERCP was moderate (kappa,
      0.40). Agreement between EUS and ERCP with EUS-TCB were poor (kappa, 0) and fair
      (kappa, 0.25), respectively. CONCLUSIONS: Transgastric EUS-TCB of suspected
      nonfocal CP infrequently demonstrates histologic CP in clinically suspected
      disease. Because of potential complications and limited diagnostic yield, this
      technique is not currently recommended for evaluation of these patients.

PMID- 15990824
TI  - Endoscopic treatment of sphincterotomy-associated distal common bile duct
      strictures by using sequential insertion of multiple plastic stents.
AB  - BACKGROUND: A rare, late complication of endoscopic biliary sphincterotomy is the
      occurrence of short strictures extending from the papillary orifice to the distal
      parts of the extraduodenal common bile duct. METHODS: We evaluated the efficacy
      of the sequential insertion of multiple stents in the treatment of endoscopic
      biliary sphincterotomy associated common bile duct strictures. The design of the
      study is a prospective, single-arm observational study at a university-affiliated
      teaching hospital of 20 patients with distal common bile duct strictures because
      of choledocholithiasis-related endoscopic biliary sphincterotomy. Endoscopic
      treatment consisted of the sequential insertion of an increasing number of
      plastic stents with ever-larger diameters in 3-month follow-up intervals until
      stricture resolution. The primary outcome of the study was the rate of resolution
      of the stricture. The parameters measured were the duration of placement of
      stents, the maximum diameter, the total number of stents, and the total number of
      endoscopic sessions required for dilation of the strictures. RESULTS: After a
      median of 9.0 months of stent placement (range 3-22 months) and a median of 20F
      maximum stent diameter (range 10F-30F), 18 patients (90%) remained stent-free for
      a median of 14.5 months (range 6-38 months). Two patients (10%) had stricture
      recurrences at 10 and 24 months. Multivariate regression analysis demonstrated
      that the time elapsed after endoscopic biliary sphincterotomy was significantly
      associated with the stent-placement time (however, significance was removed by
      correction for multiple testing) and the number of ERCPs required for dilation.
      The initial common bile duct size was significantly associated with the total
      stent number and diameter needed for stricture resolution (however, significance
      was removed by correction for multiple testing). Limitations are the low case
      number and the single-arm, noncontrolled study design. CONCLUSIONS: Sequential
      insertion of an increasing number of biliary stents affords effective treatment
      of the distal biliary strictures that develop as a late complication of
      endoscopic biliary sphincterotomy.

PMID- 15990825
TI  - Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a
      new safe and effective treatment algorithm (videos).
AB  - BACKGROUND: Pancreatic necrosis and pancreatic abscess are severe complications
      of acute pancreatitis. Surgery is associated with significant morbidity and
      mortality in these critically ill patients. Endoscopic therapy has the potential
      to offer a safer and more effective alternative treatment modality. However, its
      role needs to be further investigated. METHODS: This is a retrospective study of
      the outcome of consecutive patients with pancreatic necrosis and pancreatic
      abscess, all unfit to undergo surgery, who underwent a new aggressive endoscopic
      approach. The treatment includes (1) synchronous EUS-guided multiple transmural
      and/or transpapillary drainage procedures followed by balloon dilation of the
      cystogastrostoma or cystoduodenostoma, (2) daily endoscopic necrosectomy and
      saline solution lavage, and (3) sealing of pancreatic fistula by N-butyl-2
      cyanoacrylate. RESULTS: Pancreatic necrosis and pancreatic abscesses were
      successfully drained in 13 patients, thus avoiding emergency surgery as an
      initial treatment. Surgery was completely avoided in 9 patients over a median
      follow-up of 8.3 months (range 3-81 months). Surgery was combined with endoscopic
      therapy in one patient because of abscess extension into the right paracolic
      gutter, which was not manageable by endoscopic drainage. Because of the
      "disconnected-duct syndrome," two patients later developed recurrent pseudocysts
      and underwent elective surgery. Complications included minor bleeding after
      balloon dilation and necrosectomy in 4 cases, which were self limiting or
      controlled endoscopically. CONCLUSIONS: This aggressive endoscopic approach shows
      promising results. It expands the potential for endoscopic treatment in patients
      with pancreatic necrosis and/or pancreatic abscess.

PMID- 15990826
TI  - Endoscopic management of pancreatic necrosis: not for the uncommitted.

PMID- 15990827
TI  - Intravenous N-acetylcysteine does not prevent post-ERCP pancreatitis.
AB  - BACKGROUND: Acute pancreatitis remains the most common complication of ERCP.
      Prophylactic administration of N-acetylcysteine (NAC) probably decreases the
      incidence and the severity of experimental pancreatitis. The aim of the present
      study was to assess the efficacy of intravenous NAC for prevention of post-ERCP
      pancreatitis in humans, who represent an appropriate model to study the potential
      role of NAC in this setting. METHODS: A prospective, double-blind, placebo
      controlled trial was conducted in 256 patients who underwent ERCP. Patients were
      randomized to receive intravenous NAC at a loading dose of 70 mg/kg 2 hours
      before and 35 mg/kg at 4-hour intervals for a total of 24 hours after the
      procedure, or to receive normal saline solution as placebo. Patients were
      clinically evaluated, and serum amylase levels were measured before and 6 hours
      and 24 hours after the procedure. Standardized criteria were used to diagnose and
      to grade the severity of post-ERCP pancreatitis. RESULTS: A total of 249 patients
      were included in the analysis. The two groups were matched for age, gender,
      underlying disease and indication for treatment, ERCP findings, and type of
      treatment. The overall incidence of post-ERCP acute pancreatitis was 10.8%, with
      12.1% in the NAC group and 9.6% in the placebo group. There were no statistical
      differences in the incidence or severity grades between the groups. The mean
      duration of hospitalization for pancreatitis also was similar in the NAC group
      and the placebo group (3.6 +/- 0.9 and 3 +/- 1.5 days, respectively).
      CONCLUSIONS: The results of this trial show the absence of any beneficial effect
      of NAC on the incidence and the severity of ERCP-induced pancreatitis.

PMID- 15990828
TI  - Ambulatory endoscopy centers: what the interviewing fellow needs to know.

PMID- 15990830
TI  - No more biopsy in the diagnostic work-up of celiac disease.

PMID- 15990831
TI  - Endoscopic full-thickness resection with sutured closure in a porcine model.
AB  - BACKGROUND: Some early gastric cancers might be advantageously staged and treated
      by full-thickness resection if secure methods for closing the defect were
      available. The aim of this study was to test the feasibility of full-thickness
      gastric resection. METHODS: Full-thickness gastric resections were performed by
      using a ligating device without submucosal injection in survival studies in pigs
      (n = 8). The defects were closed by using new methods for suturing, locking, and
      cutting thread through a 2.8-mm accessory channel. Stitches (n = 2-4) were placed
      close to the target area before resection. OBSERVATIONS: Full-thickness
      resections (n = 8) were performed. The pigs survived without incident for 21 to
      28 days. Healing of the suture site was evident at follow-up endoscopy. Suture
      sites were water tight. The pull-out force with stitches by using this new sewing
      method was significantly higher than with endoscopic clips (20.3 N +/- 0.94 vs.
      2.2 N +/- 0.42, p < 0.05). CONCLUSIONS: Endoscopic full-thickness resection with
      sutured defect closure was feasible and appeared safe in these survival
      experiments.

PMID- 15990832
TI  - The evolution of endoluminal intervention.

PMID- 15990833
TI  - Handcrafted two-channel colonoscope for grasping-forceps-assisted resection of
      giant pedunculated polyps.
AB  - BACKGROUND: Colonoscopic polypectomy of giant pedunculated polyps has an
      increased risk of bleeding and is technically difficult. To facilitate the
      removal of the polyps, we handcrafted a two-channel colonoscope and applied it
      for grasping-forceps-assisted resection. METHODS: We easily handcrafted a two
      channel colonoscope by taping a plastic tube along the shaft of a standard
      colonoscope and used it for the technique in 10 patients with 12 giant
      pedunculated polyps. OBSERVATIONS: The colonoscope with forceps assistance proved
      to be satisfactory for handling detachable and polypectomy snares. Immediate
      bleeding occurred in one patient because the detachable snare could not be
      maneuvered over the polyp. In 3 patients, the plastic tube became mobile during
      the procedure because the tape that attached the tube became loose. No other
      complications occurred. CONCLUSIONS: A handcrafted two-channel colonoscope for
      grasping-forceps-assisted resection of giant pedunculated polyps is effective for
      the prevention of postpolypectomy bleeding and the reduction of technical
      difficulties.

PMID- 15990834
TI  - Pica syndrome: not only an endoscopic challenge.

PMID- 15990835
TI  - Psammomatous carcinoid tumor in the ampulla of Vater.

PMID- 15990836
TI  - Solitary minute metastasis from breast cancer mimicking primary intramucosal
      gastric signet-cell cancer.

PMID- 15990837
TI  - Pancreatic mucinous adenocarcinoma with peritoneal metastases.

PMID- 15990838
TI  - Endoscopic diagnosis of hookworm infection that caused intestinal bleeding.

PMID- 15990839
TI  - Endoscopic therapy for main pancreatic-duct rupture after Silastic-ring vertical
      gastroplasty.
AB  - BACKGROUND: Acute pancreatitis with pancreatic-duct rupture and fluid collections
      is a rare complication after Silastic ring vertical gastroplasty. It can be
      attributed to pancreatic trauma occurring during surgery. METHODS: Endoscopic
      therapy with transmural drainage of collections was performed in 4 patients who
      had undergone Silastic ring vertical gastroplasty and who had presented with
      acute pancreatitis with main pancreatic-duct rupture at the body of the pancreas.
      OBSERVATIONS: All patients had successful transmural drainage with
      cystogastrostomy, followed by stent insertion. Only one patient had a late
      recurrence because of stent migration. The major difficulty was related to
      positioning of the endoscope and the possible need of pneumatic dilation of the
      outlet channel to reach the puncture site. CONCLUSIONS: Endoscopic therapy is
      useful in acute pancreatitis with pancreatic-duct rupture after Silastic-ring
      vertical gastroplasty and, although technically difficult, could be considered as
      a first-line approach in the management of these patients.

PMID- 15990840
TI  - Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics
      infiltrating hilar cholangiocarcinoma: part of a spectrum of autoimmune
      pancreatitis?
AB  - BACKGROUND: Autoimmune pancreatitis has been designated as sclerosing
      pancreatocholangitis, because this disease shows a high prevalence of bile-duct
      lesions. We present herein the clinical characteristics of unusual cases that
      show dominant bile-duct lesions and mimicking infiltrating hilar
      cholangiocarcinomas. METHODS: Clinical and pathologic findings of 3 patients with
      immunoglobulin (Ig) G4 related sclerosing cholangitis who had no apparent
      pancreatic lesions comparable with autoimmune pancreatitis were analyzed.
      OBSERVATIONS: All patients were middle-aged or elderly individuals with slightly
      elevated serum IgG4 concentrations and showed long-segment narrowing of the bile
      duct system, mimicking infiltrating hilar cholangiocarcinoma without significant
      pancreatic change. The first patient was treated with a corticosteroid, resulting
      in amelioration of the narrowing of the bile duct. The second patient underwent
      surgery based on a diagnosis of cholangiocarcinoma. In the third patient, the
      bile-duct stricture reversed spontaneously 1 month after the drainage procedure.
      Pathologic findings of the bile ducts for all patients disclosed significant
      lymphoplasmacytic infiltration, including abundant IgG4-bearing plasma cells.
      CONCLUSIONS: The use of IgG4 immunostaining in biopsy specimens of the bile duct
      may identify the presence of corticosteroid-responsive lymphoplasmacytic
      sclerosing cholangitis.

PMID- 15990841
TI  - The healing course of thermal esophageal injury: a case report.

PMID- 15990842
TI  - Esophageal intramural hematoma: an unusual complication of endoscopic biopsy.

PMID- 15990843
TI  - Hemobilia in a patient with protein S deficiency after laparoscopic
      cholecystectomy that caused acute pancreatitis: successful endoscopic management.

PMID- 15990844
TI  - Endoscopic-guided capsule endoscopy in a patient with small-bowel varices after
      Whipple's operation.

PMID- 15990845
TI  - Heterotopic gastric tissue mimicking malignant biliary obstruction.

PMID- 15990847
TI  - Colonoscopic features of simvastatin-induced colitis suggest ischemia as an
      etiologic mechanism.

PMID- 15990846
TI  - A large polypoid arteriovenous malformation of the colon treated with a
      detachable snare: case report and review of literature.

PMID- 15990848
TI  - Endoscopic visualization of deployment of the Bravo pH System to prevent
      malplacement.

PMID- 15990849
TI  - Lymphangioma of the esophagus.

PMID- 15990850
TI  - Endoscopic mucosal incision with an insulated-tip knife for intramucosal
      esophageal dissection: case report.

PMID- 15990851
TI  - Diaphragm disease of small intestine diagnosed by double-balloon enteroscopy.

PMID- 15990852
TI  - Duodenal duplication cyst mimicking pancreatic cyst in a patient with
      pancreatitis.

PMID- 15990853
TI  - Intrasplenic pancreatic abscess successfully treated by endoscopic transpapillary
      drainage through the minor papilla.

PMID- 15990855
TI  - Is epinephrine the best solution for large-volume endoscopic injection of peptic
      ulcer bleeding?

PMID- 15990856
TI  - Take your Pill(Cam): it might save your life.

PMID- 15990857
TI  - Predictors of cecal intubation time.

PMID- 15990859
TI  - C5L2 receptor is not involved in C3a / C3a-desArg-mediated enhancement of bone
      marrow hematopoietic cell migration to CXCL12.

PMID- 15990860
TI  - Induction of centrosome and chromosome aberrations by imatinib in vitro.
AB  - Imatinib (STI571, Gleevec/Glivec) is a potent selective tyrosine kinase inhibitor
      and is used successfully in the treatment of chronic myeloid leukemia (CML).
      While karyotype alterations, in addition to the Philadelphia chromosome, are a
      common phenomenon of progressing CML, the observation of BCR-ABL-negative
      leukemic clones with distinct aberrant karyotypes under an imatinib regimen is
      not yet understood. Here we test the hypothesis that such tumor clones may be
      induced de novo from normal cells by imatinib. In vitro experiments with varying
      drug concentrations (5-20 microM) were performed on normal human dermal
      fibroblasts (NHDF), Chinese hamster embryonal and Indian muntjak fibroblasts.
      After 3 weeks of treatment, analysis of cell cultures by centrosome
      immunostaining and conventional cytogenetics revealed that imatinib induced
      centrosome and chromosome aberrations in all cultures in a significant dose
      dependent and species-independent manner. Moreover, the results of NHDF long-term
      culture experiments demonstrated that aberrant phenotypes, emerging under
      imatinib treatment for 12 weeks, were not reversible after prolonged propagation
      omitting the drug. These observations suggest a causative role of imatinib in the
      origin of centrosome and karyotype aberrations (genetic instability) and thus may
      explain the emergence of clonal chromosomal abnormalities in BCR-ABL-negative
      progenitor cells under imatinib therapy.

PMID- 15990861
TI  - Allogeneic dendritic cells pulsed with tumor lysates or apoptotic bodies as
      immunotherapy for patients with early-stage B-cell chronic lymphocytic leukemia.
AB  - Recently, immunotherapies with allogeneic dendritic cells (DCs) pulsed with tumor
      antigens to generate specific T-cell responses have been tested in clinical
      trials for patients with solid tumors. This is the first report on a clinical
      vaccination study with DCs for patients with B-cell chronic lymphocytic leukemia
      (B-CLL). The potential of allogeneic DCs pulsed ex vivo with tumor cell lysates
      or apoptotic bodies to stimulate antitumor immunity in patients with B-CLL in
      early stages was evaluated. Monocyte-derived DCs were obtained from unrelated
      healthy donors. Nine patients (clinical stage 0 and 1 according to Rai) were
      vaccinated five times with a mean number of 32 x 10(6) stimulated DCs
      administered intradermally once every 2-3 weeks. No signs of autoimmunity were
      detected, and only mild local skin reactions were noted. During the treatment
      period, we observed a decrease of peripheral blood leukocytes and CD19+/CD5+
      leukemic cells. In one patient, a significant increase of specific cytotoxic T
      lymphocytes against RHAMM/CD168, a recently characterized leukemia-associated
      antigen, could be detected after DC vaccination. Taken together, the study
      demonstrated that DC vaccination in CLL patients is feasible and safe.
      Immunological and to some extent hematological responses could be noted,
      justifying further investigation on this immuno-therapeutical approach.

PMID- 15990862
TI  - Age has a profound effect on the incidence and significance of chromosome
      abnormalities in myeloma.
AB  - A simple high throughput micro-fluorescence in situ hybridisation technique
      (FISH) was used to detect chromosome 13 deletions (delta13), immunoglobulin heavy
      chain (IgH) rearrangements, t(11;14)(q13;q32), t(4;14)(p16;q32),
      t(14;16)(q23;q32), p53 loss, and numerical changes of chromosomes 3, 6, 7, 9, 10,
      11 and 17 in 228 cases of multiple myeloma (MM), including 33
      asymptomatic/smouldering MM (SMM). The patients were not part of a clinical trial
      and were from 30 different hospitals. In all, 98.4% of cases were abnormal, with
      43% having IgH rearrangements and 42% Delta13. The low incidence of IgH
      rearrangements was due to a decrease in this finding with age (P = 0.001) and the
      relatively high proportion of elderly patients in our study population (41% >70
      years old). The incidence of specific IgH translocations was t(4;14) 11%,
      t(11;14) 16% and t(14;16) 3%. Univariate statistical testing showed delta13 (P =
      0.002), and t(14;16) (P = 0.005) to be associated with shorter survival. This
      effect was exaggerated for patient's aged 70 years or under but no effect on
      survival was seen for those over 70 years. In younger patients t(4;14) (P =
      0.044) and p53 deletion (P < 0.001) were also significant poor prognostic
      indicators. Multivariate analysis showed delta13 and t(14;16) to be independent
      prognostic variables when considered with age and clinical parameters.

PMID- 15990863
TI  - Chronic graft-versus-host disease: where is promise for the future?

PMID- 15990864
TI  - Combination of imatinib with rapamycin or RAD001 acts synergistically only in Bcr
      Abl-positive cells with moderate resistance to imatinib.

PMID- 15990865
TI  - CIZ gene rearrangements in acute leukemia: report of a diagnostic FISH assay and
      clinical features of nine patients.

PMID- 15990866
TI  - p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large
      cell lymphoma.
AB  - Anaplastic large-cell lymphoma (ALCL), as defined in the World Health
      Organization, is a heterogeneous category in which a subset of cases is
      associated with the t(2;5)(p23;q35) or variant translocations resulting in
      overexpression of anaplastic lymphoma kinase (ALK). p53 has not been assessed in
      currently defined subsets of ALCL tumors. In this study, we assessed ALK+ and ALK
      ALCL tumors for p53 gene alterations using PCR, single-strand conformation
      polymorphism and direct sequencing methods. We also immunohistochemically
      assessed ALCL tumors for p53 expression. Three of 36 (8%) ALCL tumors (1/14 ALK+,
      2/22 ALK-) with adequate DNA showed p53 gene mutations. By contrast, p53 was
      overexpressed in 36 of 55 (65%) ALCL tumors (16 ALK+, 20 ALK-). p21, a target of
      p53, was expressed in 15 of 31 (48%) ALCL tumors including seven of 15 (47%) p53
      positive tumors. p21 expression in a subset of ALCL suggests the presence of
      functional p53 protein. Apoptotic rate was significantly higher in p53-positive
      than p53-negative tumors (mean 2.78 vs 0.91%, P = 0.0003). We conclude that the
      p53 gene is rarely mutated in ALK+ and ALK- ALCL tumors. Nevertheless, wild-type
      p53 gene product is commonly overexpressed in ALCL and may be functional in a
      subset of these tumors.

PMID- 15990867
TI  - Significance of HOX11L2/TLX3 expression in children with T-cell acute
      lymphoblastic leukemia treated on Children's Cancer Group protocols.

PMID- 15990868
TI  - A 10-year median follow-up study after allogeneic stem cell transplantation for
      chronic myeloid leukemia in chronic phase from HLA-identical sibling donors.
AB  - We report long-term outcome in 102 patients with cCML transplanted from an HLA
      identical sibling donor from 1982 to 1998. The conditioning regimen was based on
      cyclophosphamide associated with either total body irradiation (TBI) (37
      patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD)
      prophylaxis consisted of cyclosporin and methotrexate in the majority of the
      patients. Fifteen year overall survival was estimated at 53% (95% confidence
      interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was
      adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis
      to transplantation, older age at time of transplantation and GvHD (acute grade
      III-IV or chronic extensive). The main cause of death was infection, related to
      GvHD in 69% of patients. Splenectomy also significantly increased the risk of
      bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late
      malignancies occurred in seven patients, four of whom had an invasive cancer.
      Other frequent late complications included cataracts, psychological depression,
      osteonecrosis and hypothyroidism. These complications were more frequent
      following splenectomy, TBI and in patients with chronic extensive GvHD. We
      conclude that allogeneic transplantation with a related donor can cure more than
      half of CML patients in chronic phase, although physicians should be alert to
      long-term complications.

PMID- 15990869
TI  - Stress response gene ATF3 is a target of c-myc in serum-induced cell
      proliferation.
AB  - The c-myc proto-oncogene encodes a transcription factor that promotes cell cycle
      progression and cell proliferation, and its deficiency results in severely
      retarded proliferation rates. The ATF3 stress response gene encodes a
      transcription factor that plays a role in determining cell fate under stress
      conditions. Its biological significance in the control of cell proliferation and
      its crosstalk regulation, however, are not well understood. Here, we report that
      the serum response of the ATF3 gene expression depends on c-myc gene and that the
      c-Myc complex at ATF/CREB site of the gene promoter plays a role in mediating the
      serum response. Intriguingly, ectopic expression of ATF3 promotes proliferation
      of c-myc-deficient cells, mostly by alleviating the impeded G1-phase progression
      observed in these cells, whereas ATF3 knockdown significantly suppresses
      proliferation of wild-type cells. Our study demonstrates that ATF3 is downstream
      of the c-Myc signaling pathway and plays a role in mediating the cell
      proliferation function of c-Myc. Our results provide a novel insight into the
      functional link of the stress response gene ATF3 and the proto-oncogene c-myc.

PMID- 15990870
TI  - Identification and characterization of novel nicotinic receptor-associated
      proteins in Caenorhabditis elegans.
AB  - Nicotinic acetylcholine receptors (nAChRs) mediate fast excitatory
      neurotransmission in neurons and muscles. To identify nAChR accessory proteins,
      which may regulate their expression or function, we performed tandem affinity
      purification of the levamisole-sensitive nAChR from Caenorhabditis elegans, mass
      spectrometry of associated components, and RNAi-based screening for effects on in
      vivo nicotine sensitivity. Among the proteins identified was the calcineurin A
      subunit TAX-6, which appeared to function as a negative regulator of nAChR
      activity. We also identified five proteins not previously linked to nAChR
      function, whose inactivation conferred nicotine resistance, implicating them as
      positive regulators of nAChR activity. Of these, the copine NRA-1 colocalized
      with the levamisole receptor at neuronal and muscle plasma membranes, and, when
      mutated, caused reduced synaptic nAChR expression. Loss of SOC-1, which acts in
      receptor tyrosine kinase (RTK) signaling, also reduced synaptic levamisole
      receptor levels, as did mutations in the fibroblast growth factor receptor EGL
      15, and another RTK, CAM-1. Thus, tandem affinity purification is a viable
      approach to identify novel proteins regulating neurotransmitter receptor activity
      or expression in model systems like C. elegans.

PMID- 15990871
TI  - The HRDC domain of BLM is required for the dissolution of double Holliday
      junctions.
AB  - Bloom's syndrome is a hereditary cancer-predisposition disorder resulting from
      mutations in the BLM gene. In humans, BLM encodes one of five members of the RecQ
      helicase family. One function of BLM is to act in concert with topoisomerase
      IIIalpha (TOPO IIIalpha) to resolve recombination intermediates containing double
      Holliday junctions by a process called double Holliday junction dissolution,
      herein termed dissolution. Here, we show that dissolution is highly specific for
      BLM among human RecQ helicases and critically depends upon a functional HRDC
      domain in BLM. We show that the HRDC domain confers DNA structure specificity,
      and is required for the efficient binding to and unwinding of double Holliday
      junctions, but not for the unwinding of a simple partial duplex substrate.
      Furthermore, we show that lysine-1270 of BLM, which resides in the HRDC domain
      and is predicted to play a role in mediating interactions with DNA, is required
      for efficient dissolution.

PMID- 15990872
TI  - Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin.
AB  - FKBP-type peptidyl prolyl cis/trans isomerases (PPIases) are folding helper
      enzymes involved in the control of functional regrowth of damaged sciatic,
      cortical cholinergic, dopaminergic and 5-HT neurones. Here, we show that the
      constitutively inactive human FK506-binding protein 38 (FKBP38) is capable of
      responding directly to intracellular Ca2+ rise through formation of a
      heterodimeric Ca2+/calmodulin/FKBP38 complex. Only complex formation creates an
      enzymatically active FKBP, displaying affinity for Bcl-2 mediated through the
      PPIase site. Association between Bcl-2 and the active site of
      Ca2+/calmodulin/FKBP38 regulates Bcl-2 function and thereby participates in the
      promotion of apoptosis in neuronal tissues. FKBP38 proapoptotic function mediated
      by this interaction is abolished by either potent inhibitors of the PPIase
      activity of the Ca2+/calmodulin/FKBP38 complex or RNA interference-mediated
      depletion of FKBP38, promoting neuronal cell survival.

PMID- 15990873
TI  - The MAP kinase substrate MKS1 is a regulator of plant defense responses.
AB  - Arabidopsis MAP kinase 4 (MPK4) functions as a regulator of pathogen defense
      responses, because it is required for both repression of salicylic acid (SA)
      dependent resistance and for activation of jasmonate (JA)-dependent defense gene
      expression. To understand MPK4 signaling mechanisms, we used yeast two-hybrid
      screening to identify the MPK4 substrate MKS1. Analyses of transgenic plants and
      genome-wide transcript profiling indicated that MKS1 is required for full SA
      dependent resistance in mpk4 mutants, and that overexpression of MKS1 in wild
      type plants is sufficient to activate SA-dependent resistance, but does not
      interfere with induction of a defense gene by JA. Further yeast two-hybrid
      screening revealed that MKS1 interacts with the WRKY transcription factors WRKY25
      and WRKY33. WRKY25 and WRKY33 were shown to be in vitro substrates of MPK4, and a
      wrky33 knockout mutant was found to exhibit increased expression of the SA
      related defense gene PR1. MKS1 may therefore contribute to MPK4-regulated defense
      activation by coupling the kinase to specific WRKY transcription factors.

PMID- 15990874
TI  - Metabolon disruption: a mechanism that regulates bicarbonate transport.
AB  - Carbonic anhydrases (CA) catalyze the reversible conversion of CO2 to HCO3-. Some
      bicarbonate transporters bind CA, forming a complex called a transport metabolon,
      to maximize the coupled catalytic/transport flux. SLC26A6, a plasma membrane Cl
      /HCO3- exchanger with a suggested role in pancreatic HCO3- secretion, was found
      to bind the cytoplasmic enzyme CAII. Mutation of the identified CAII binding
      (CAB) site greatly reduced SLC26A6 activity, demonstrating the importance of the
      interaction. Regulation of SLC26A6 bicarbonate transport by protein kinase C
      (PKC) was investigated. Angiotensin II (AngII), which activates PKC, decreased Cl
      /HCO3- exchange in cells coexpressing SLC26A6 and AT1a-AngII receptor. Activation
      of PKC reduced SLC26A6/CAII association in immunoprecipitates. Similarly, PKC
      activation displaced CAII from the plasma membrane, as monitored by
      immunofluorescence. Finally, mutation of a PKC site adjacent to the SLC26A6 CAB
      site rendered the transporter unresponsive to PKC. PKC therefore reduces
      CAII/SLC26A6 interaction, reducing bicarbonate transport rate. Taken together,
      our data support a mechanism for acute regulation of membrane transport:
      metabolon disruption.

PMID- 15990875
TI  - Repression of Runx2 function by TGF-beta through recruitment of class II histone
      deacetylases by Smad3.
AB  - Transforming growth factor-beta (TGF-beta) inhibits osteoblast differentiation
      through inhibition of the function of Runx2 (Cbfa1) by Smad3. The mechanism
      through which TGF-beta/Smad3 inhibits Runx2 function has not been characterized.
      We show that TGF-beta induces histone deacetylation, primarily of histone H4, at
      the osteocalcin promoter, which is repressed by TGF-beta, and that histone
      deacetylation is required for repression of Runx2 by TGF-beta. This repression
      occurs through the action of the class IIa histone deacetylases (HDAC)4 and 5,
      which are recruited through interaction with Smad3 to the Smad3/Runx2 complex at
      the Runx2-binding DNA sequence. Accordingly, HDAC4 or 5 is required for efficient
      TGF-beta-mediated inhibition of Runx2 function and is involved in osteoblast
      differentiation. Our results indicate that class IIa HDACs act as corepressors
      for TGF-beta/Smad3-mediated transcriptional repression of Runx2 function in
      differentiating osteoblasts and are cell-intrinsic regulators of osteoblast
      differentiation.

PMID- 15990878
TI  - Pause for postdocs.

PMID- 15990877
TI  - Homolog of BRCA2-interacting Dss1p and Uap56p link Mlo3p and Rae1p for mRNA
      export in fission yeast.
AB  - The breast cancer tumor suppressor BRCA2-interacting protein, DSS1, and its
      homologs are critical for DNA recombination in eukaryotic cells. We found that
      Dss1p, along with Mlo3p and Uap56p, Schizosaccharomyces pombe homologs of two
      messenger RNA (mRNA) export factors of the NXF-NXT pathway, is required for mRNA
      export in S. pombe. Previously, we showed that the nuclear pore-associated Rae1p
      is an essential mRNA export factor in S. pombe. Here, we show that Dss1p and
      Uap56p function by linking mRNA adapter Mlo3p to Rae1p for targeting mRNA-protein
      complex (mRNP) to the proteins of the nuclear pore complex (NPC). Dss1p
      preferentially recruits to genes in vivo and interacts with -FG (phenylalanine
      glycine) nucleoporins in vivo and in vitro. Thus, Dss1p may function at multiple
      steps of mRNA export, from mRNP biogenesis to their targeting and translocation
      through the NPC.

PMID- 15990876
TI  - Chromatin regulation and sumoylation in the inhibition of Ras-induced vulval
      development in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans, numerous 'synMuv' (synthetic multivulval) genes encode
      for chromatin-associated proteins involved in transcriptional repression,
      including an orthologue of Rb and components of the NuRD histone deacetylase
      complex. These genes antagonize Ras signalling to prevent erroneous adoption of
      vulval fate. To identify new components of this mechanism, we performed a genome
      wide RNA interference (RNAi) screen. After RNAi of 16 757 genes, we found nine
      new synMuv genes. Based on predicted functions and genetic epistasis experiments,
      we propose that at least four post-translational modifications converge to
      inhibit Ras-stimulated vulval development: sumoylation, histone tail
      deacetylation, methylation, and acetylation. In addition, we demonstrate a novel
      role for sumoylation in inhibiting LIN-12/Notch signalling in the vulva. We
      further show that many of the synMuv genes are involved in gene regulation
      outside the vulva, negatively regulating the expression of the Delta homologue
      lag-2. As most of the genes identified in this screen are conserved in humans, we
      suggest that similar interactions may be relevant in mammals for control of Ras
      and Notch signalling, crosstalk between these pathways, and cell proliferation.

PMID- 15990879
TI  - Misreading race and genomics after BiDil.

PMID- 15990881
TI  - RNA polymerase IV and transcriptional silencing.

PMID- 15990882
TI  - Vive la difference!

PMID- 15990883
TI  - A delay like no other.

PMID- 15990884
TI  - A new TRP to kidney disease.

PMID- 15990885
TI  - Resistance is futile.

PMID- 15990888
TI  - Priorities and standards in pharmacogenetic research.
AB  - The current enthusiasm for pharmacogenetics draws much of its inspiration from
      the relatively few examples of polymorphisms that have marked and seemingly
      clinically relevant effects on drug response. In this regard, pharmacogenetic
      research has paralleled the study of human disease, which has enjoyed success in
      identifying mutations underlying mendelian conditions. Progress in deciphering
      the genetics of complex diseases, involving the interaction of multiple genes
      with each other and with the environment has been considerably less successful.
      In most instances, drug responses will probably also prove to be complex,
      influenced by both the environment and multiple genetic factors. For
      pharmacogenetics to deliver on its potential, this complexity will need to be
      recognized and accommodated, both in basic research and in clinical application
      of pharmacogenetics. As the attention of researchers begins to shift toward more
      systematic pharmacogenetic investigations, we suggest some priorities and
      standards for pharmacogenetic research.

PMID- 15990889
TI  - Databases in peril.

PMID- 15990890
TI  - Moving forward with cell migration.

PMID- 15990891
TI  - Viral entry: a detour through multivesicular bodies.

PMID- 15990892
TI  - RNAi and the P-body connection.

PMID- 15990893
TI  - A central role for S-nitrosylation in apoptosis.

PMID- 15990895
TI  - Nbs1 moving up in the world.

PMID- 15990898
TI  - Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian
      approach.
AB  - Tumor lymphatic density is evaluated by means of specific lymphatic endothelium
      markers, and is a potential predictor of clinically meaningful outcomes. There
      are many claims on the postulated superiority of some of these markers to
      identify lymphatics, always in the absence of quantitative data. We therefore
      compared the diagnostic accuracy of the antibody against podoplanin and the
      commercially available D2-40, employing Bayesian statistics to account for the
      absence of a gold standard. We used the pan-endothelial marker CD34 to identify
      23,542 distinct blood and lymphatic vessels in sections from 30 formalin-fixed,
      paraffin-embedded archival tissue blocks of head and neck squamous cell carcinoma
      specimens. We stained two adjacent sections with podoplanin and D2-40 and
      identified the continuum of each stained vessel in the sections with a
      comprehensive method. Overall, 1,864 vessels were stained with both markers, 119
      only with podoplanin and 391 only with D2-40. Significantly more vessels with
      intraluminal red blood cells were stained with D2-40 compared to podoplanin
      (McNemar's P<0.0001). Both antibodies had extremely high specificity (99.7% (95%
      credible interval (CrI): 99.5-99.9%) and 98.8% (95% CrI: 98.3-99.5%) for
      podoplanin and D2-40, respectively) and very high sensitivity (92.6% (95% CrI:
      86.1-97.9%) and 97.3% (95% CrI: 94.9-99.2%) for podoplanin and D2-40,
      respectively). Inferences were qualitatively similar when we took into account in
      the analyses the possibility that the two tests (antibodies) may be correlated.
      We calculated that 96.3% (95% CrI: 94.2-98.6%) of the vessels stained with
      podoplanin and 88.9% (95% CrI: 83.9-95.7%) of the vessels stained with D2-40 were
      truly lymphatics. These numbers were in agreement with the observed number of
      stained vessels without intraluminal red blood cells. Our results suggest that
      both antibodies are excellent lymphatic endothelium markers and that there may be
      little reason to prefer either of them in most settings.

PMID- 15990899
TI  - Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1
      tumors.
AB  - Breast ducts contain two types of epithelial cells, inner luminal cells and outer
      basal/myoepithelial cells. These cells can be distinguished by their
      immunophenotype. Cytokeratins (CKs) 8 and 18 are expressed in the luminal layer,
      whereas CK5/14 and the transcription factor p63 characterize the basal epithelial
      layer. We studied a population-based cohort of 288 sporadic ductal invasive
      cancers and found 9% positive for CK5/14 and 4% positive for p63. Using a highly
      sensitive polymer-based immunohistochemical staining, all sporadic tumors were
      positive for the luminal CK8/18, including those positive for CK5/14. Pairs of
      primary tumors and metastases (n = 38) were always concordant for CK5/14
      expression. The majority of the CK5/14-positive cases were of histologic grade
      III (P = 0.0007) and steroid hormone receptor negative (P < 0.0001). CK5/14
      expression was inversely associated with HER-2 oncogene amplification, but only
      in the subgroup of estrogen receptor-negative tumors (P = 0.007). In a separate
      set of 42 hereditary breast cancers, the majority (78%) of the BRCA1-associated
      tumors, but only one of 15 BRCA2-associated tumors was positive for CK5/14. In
      contrast to sporadic CK5/14-positive tumors, BRCA1-associated tumors displayed
      less intense CK8/18 staining, including some truly CK5/14-positive CK8/18
      negative cases. These results suggest that CK5/14-positive sporadic breast
      cancers arise from glandularly committed progenitor cells rather than true CK8/18
      negative basal cells.

PMID- 15990900
TI  - Highs and lows.

PMID- 15990901
TI  - Bereaved caregivers' descriptions of sleep: impact on daily life and the
      bereavement process.
AB  - PURPOSE/OBJECTIVES: To describe how sleep and bereavement may be related in
      family caregivers. DESIGN: Descriptive and qualitative. SETTING: Participants'
      homes. SAMPLE: 9 adults with no previous diagnoses of clinical depression or
      sleep disorders who had been providing care to family members who died in the
      previous six months. METHODS: Participants provided narrative accounts of sleep
      quality, bereavement, and daily functioning since the death of their family
      members. Participants' sleep quality and depressive symptoms also were measured
      with the Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiological
      Studies-Depression Scale (CES-D). MAIN RESEARCH VARIABLES: Sleep quality,
      depressive symptoms, bereavement, and daily functioning. FINDINGS: Narratives
      revealed five themes: nightmares, wake after sleep onset, scheduling, daily life,
      and bereavement. Participants scored high on the PSQI and CES-D. CONCLUSIONS:
      Sleep quality appears to affect bereavement and daily functioning. Participants
      reported severe levels of sleep disturbance and depressive symptoms. IMPLICATIONS
      FOR NURSING: Studies are needed to explore sleep quality in bereaved caregivers
      and to examine the relationship between sleep quality and an individual's ability
      to accomplish the tasks of bereavement.

PMID- 15990902
TI  - Oncology Nursing Society environmental scan 2004.

PMID- 15990903
TI  - Helping families of patients with cancer.
AB  - PURPOSE/OBJECTIVES: To discuss the impact of cancer on families of patients with
      cancer. DATA SOURCES: National reports on caregiving and research articles
      related to cancer and families. DATA SYNTHESIS: Family caregivers are the bedrock
      of chronic care in the United States. They provide an enormous amount of unpaid
      care that is often invisible. Cancer can affect the emotional, social, physical,
      and spiritual well-being of family members. CONCLUSIONS: Family intervention
      research can have a positive effect on patient and family caregiver outcomes.
      More intervention research with families is needed that is theoretically based,
      uses randomized clinical trial designs, and uses instruments that are sensitive
      to intervention effects. IMPLICATIONS FOR NURSING: Although family intervention
      research is limited, descriptive and exploratory research has identified
      protective factors and risk factors that need to be addressed in clinical
      practice.

PMID- 15990904
TI  - Quality of informed consent: measuring understanding among participants in
      oncology clinical trials.
AB  - PURPOSE/OBJECTIVES: To describe newly enrolled clinical trial subjects' knowledge
      and understanding of the oncology clinical trials in which they were
      participating. DESIGN: Descriptive, correlational. SETTING: The oncology center
      of a small community hospital in New England. SAMPLE: 8 patients who consented to
      enroll in oncology clinical trials. METHODS: The Quality of Informed Consent
      questionnaire was sent to 17 potential participants who recently had consented to
      participate in oncology clinical trials. MAIN RESEARCH VARIABLES: Knowledge of
      the basic elements of informed consent and participants' understanding of the
      clinical trials in which they were enrolled. FINDINGS: Scores on the Quality of
      Informed Consent questionnaire indicated that participants had a good overall
      understanding of the basic elements of informed consent as well as the clinical
      trials in which they were enrolled. However, half of the sample failed to
      understand that clinical trial treatment is not standard treatment and may
      involve additional risk when compared with standard treatment. CONCLUSIONS: The
      results of this investigation provide valuable feedback regarding participants'
      understanding of the informed consent process. The Quality of Informed Consent
      questionnaire may be a useful tool for monitoring the quality of the informed
      consent process and contributing to patients' understanding of clinical trials
      and the research process. IMPLICATIONS FOR NURSING: The Quality of Informed
      Consent questionnaire may provide valuable feedback regarding clinical trial
      participants' understanding of clinical trials and the research process.
      Individual responses to questions on the questionnaire may be used to aid
      personalized patient education and validation of the informed consent throughout
      trial enrollment. Future research efforts need to focus on the development of
      reliable tools to measure participants' understanding of informed consent and
      nursing interventions that improve the informed consent process as well as
      enhance patients' understanding of the research process.

PMID- 15990905
TI  - Relative dose intensity: improving cancer treatment and outcomes.
AB  - PURPOSE/OBJECTIVES: To determine the incidence of and reasons for chemotherapy
      dose delays or reductions. DESIGN: A performance improvement initiative formed
      the basis for a prospective nursing research study. SETTING: A single institution
      in western Pennsylvania. SAMPLE: 204 patients scheduled for nonmyeloablative
      chemo-therapy. METHODS: Data collection forms were completed by RNs and evaluated
      by an interdisciplinary team. MAIN RESEARCH VARIABLES: Rates of nonadherence to
      chemotherapy schedule or dosing and associated reasons. FINDINGS: The performance
      improvement initiative revealed evidence of nonadherence to chemotherapy schedule
      or dosing when patient-requested cancellations and physician-ordered dose delays
      and reductions were left unchallenged and medical and nursing staffs had limited
      knowledge of or interest in relative dose intensity. The ensuing nursing research
      study found that less than 51% and 78% of patients adhered to their schedule and
      dosage, respectively. Nonadherence primarily was attributed to canceled visits,
      suboptimal or nonuse of hematopoietic growth factors, and routine dose
      reductions. Subsequent educational initiatives targeting the interdisciplinary
      team and patients and their families focused on the importance of keeping
      scheduled visits and preventing versus managing pancytopenia. Adopting a
      telephone referral procedure and distributing a patient education sheet reduced
      patient cancellations by 50%. Various reasons for dose delays and reductions have
      surfaced, many of which are modifiable with educational efforts. CONCLUSIONS: A
      knowledge deficit was found among patients and healthcare providers regarding the
      importance of adhering to chemo-therapy orders. IMPLICATIONS FOR NURSING:
      Evaluating patterns of chemotherapy administration and educating patients,
      nurses, and physicians will have an impact on relative dose intensity,
      potentially improving treatment outcomes.

PMID- 15990906
TI  - Nurse practice environments and outcomes: implications for oncology nursing.
AB  - PURPOSE/OBJECTIVES: To examine practice environments and outcomes of nurses
      working in oncology units or Magnet hospitals and to understand the association
      between the two. DESIGN: Secondary analysis of survey data collected in 1998.
      SETTING: Medical and surgical units of 22 hospitals, of which 7 were recognized
      by the American Nurses Credentialing Center Magnet program. SAMPLE: 1,956 RNs, of
      whom 305 worked in oncology units. METHODS: Chi-square tests compared nurse
      reported outcomes by work setting, analysis of variance tested practice
      environment differences by setting, and logistic regression estimated the effects
      of practice environment, specialty, and Magnet status on outcomes. MAIN RESEARCH
      VARIABLES: Practice environments, emotional exhaustion, job satisfaction, and
      quality of care. FINDINGS: Oncology nurses had superior outcomes compared with
      nononcology nurses. Emotional exhaustion was significantly lower among oncology
      nurses working in Magnet hospitals. Scores on the Collegial Nurse-Physician
      Relations subscale were highest among oncology nurses. Outcomes were associated
      with Practice Environment Scale of the Nursing Work Index scores and Magnet
      status. Oncology nurses with favorable collegial nurse-physician relations were
      twice as likely to report high-quality care. CONCLUSIONS: Oncology nurses benefit
      from working in American Nurses Credentialing Center Magnet hospitals. Adequate
      staffing and resources are necessary to achieve optimal outcomes. Collegial nurse
      physician relations appear to be vital to optimal oncology practice settings.
      IMPLICATIONS FOR NURSING: In addition to pursuing American Nurses Credentialing
      Center Magnet recognition, nurse managers should assess practice environments and
      target related interventions to improve job satisfaction and retention. High
      priority areas for interventions include ensuring adequate staff and resources,
      promoting nurse-physician collaboration, and strengthening unit-based leadership.

PMID- 15990907
TI  - Nursing sensitive patient outcomes--a white paper.

PMID- 15990908
TI  - Dyspnea management in lung cancer: applying the evidence from chronic obstructive
      pulmonary disease.
AB  - PURPOSE/OBJECTIVES: To provide an overview of mechanisms of dyspnea and causes of
      dyspnea in chronic obstructive pulmonary disease (COPD) and lung cancer and to
      critically review current pharmacologic and nonpharmacologic management of
      dyspnea for COPD and lung cancer. DATA SOURCES: Published articles, abstracts,
      textbooks, and the authors' personal experiences with dyspnea management in COPD
      and lung cancer. DATA SYNTHESIS: The causes of dyspnea in cancer are more varied
      than the causes of dyspnea in COPD; however, many are similar, thus providing the
      justification for recommending best practice from COPD research to be used in
      lung cancer. Dyspnea in both diseases is treated by corticosteroids,
      bronchodilators, antianxiety drugs, local anesthetics, and oxygen. However, when
      dyspnea is severe, morphine is the first choice. Using specific breathing
      techniques, positioning, energy conservation, exercise, and some dietary
      modifications and nutrient supplements can help with dyspnea management.
      CONCLUSIONS: Pharmacologic and nonpharmacologic management of dyspnea in COPD can
      be applied to dyspnea related to lung cancer. Further research in the management
      of dyspnea in lung cancer is required, particularly controlled studies with
      larger sample sizes, to determine the effectiveness of the application of COPD
      dyspnea management in lung cancer. IMPLICATIONS FOR NURSING: Previous studies
      provide a guideline for applying dyspnea management for COPD to cancer. The
      theoretical frameworks used in previous studies can be modified for conducting
      further study.

PMID- 15990909
TI  - Age differences in treatment decision making for breast cancer in a sample of
      healthy women: the effects of body image and risk framing.
AB  - PURPOSE/OBJECTIVES: To examine the effects of age, body image, and risk framing
      on treatment decision making for breast cancer using a healthy population.
      DESIGN: An experimental 2 (younger women, older women) X 2 (survival, mortality
      frame) between-groups design. SETTING: Midwestern university. SAMPLE: Two groups
      of healthy women: 56 women ages 18-24 from undergraduate psychology courses and
      60 women ages 35-60 from the university community. METHODS: Healthy women
      imagined that they had been diagnosed with breast cancer and received information
      regarding lumpectomy versus mastectomy and recurrence rates. Participants
      indicated whether they would choose lumpectomy or mastectomy and why. MAIN
      RESEARCH VARIABLES: Age, framing condition, treatment choice, body image, and
      reasons for treatment decision. FINDINGS: The difference in treatment selection
      between younger and older women was mediated by concern for appearance. No main
      effect for risk framing was found; however, older women were somewhat less likely
      to select lumpectomy when given a mortality frame. CONCLUSIONS: Age, mediated by
      body image, influences treatment selection of lumpectomy versus mastectomy.
      Framing has no direct effect on treatment decisions, but younger and older women
      may be affected by risk information differently. IMPLICATIONS FOR NURSING: Nurses
      should provide women who recently have been diagnosed with breast cancer with age
      appropriate information regarding treatment alternatives to ensure women's active
      participation in the decision-making process. Women who have different levels of
      investment in body image also may have different concerns about treatment, and
      healthcare professionals should be alert to and empathetic of such concerns.

PMID- 15990910
TI  - Social cognitive theory and physical activity during breast cancer treatment.
AB  - PURPOSE/OBJECTIVES: To measure the association between physical activity and
      social cognitive theory constructs during breast cancer treatment. DESIGN: Cross
      sectional survey. SETTING: Midwestern, academic oncology clinic. SAMPLE: 21
      primarily Caucasian (90%) female patients with breast cancer undergoing
      treatment. 76% were > 50 years old; 76% had stage I or II disease. 17 completed
      the study. METHODS: Survey (structured interview or self-administration), chart
      audit, pedometer, and seven-day physical activity recall. MAIN RESEARCH
      VARIABLES: Steps per day, energy expenditure, self-efficacy, barriers, partners
      and role models, prior physical activity counseling, physical activity knowledge,
      pretreatment physical activity, outcome expectations and values, goals,
      reinforcement management, and emotional well-being. FINDINGS: A higher average of
      steps per day was significantly associated with having an exercise role model and
      higher annual income. A higher daily energy expenditure (kilocalories per
      kilogram body weight per day) was significantly associated with higher barrier
      self-efficacy, higher task self-efficacy, having an exercise partner, having an
      exercise role model, higher physical activity enjoyment, and lower negative value
      score. CONCLUSIONS: Social cognitive theory may provide a useful framework for
      understanding physical activity among patients with breast cancer during
      treatment, but correlation strength varies with physical activity measurement
      type. IMPLICATIONS FOR NURSING: Social cognitive theory and physical activity
      during breast cancer treatment warrant additional study with larger sample sizes
      and multivariate analyses. Interventions to increase physical activity among
      patients with breast cancer may use social cognitive theory and assess theory
      constructs as potential mediators or moderators in intervention evaluation.

PMID- 15990911
TI  - The effect of telephone social support and education on adaptation to breast
      cancer during the year following diagnosis.
AB  - PURPOSE/OBJECTIVES: To find the most effective methods of providing social
      support for women diagnosed with breast cancer by testing the effectiveness of a
      telephone social support and education intervention to promote emotional and
      interpersonal adaptation to breast cancer. DESIGN: Multisite, two-group
      experimental study with repeated measures. SETTING: Arkansas and New Jersey.
      SAMPLE: The Arkansas sample consisted of 106 women who entered the study two to
      four weeks postsurgery for nonmetastatic breast cancer and were randomly assigned
      to an experimental or control group. The comparison group consisted of 91 women
      from New Jersey who had participated in a previously completed study that used
      the same interventions and found that telephone support resulted in more
      positive, statistically significant adaptation to the disease. METHODS: The
      experimental group received 13 months of telephone social support and education.
      Both groups received educational materials via a mailed resource kit. The Profile
      of Mood States; Visual Analogue Scale-Worry; Relationship Change Scale;
      University of California, Los Angeles, Loneliness Scale-Version 3; and the
      modified Symptom Distress Scale provided data regarding the variables of
      interest. Data analysis included descriptive statistics, t tests, and
      multivariate analysis of variance with repeated measures. MAIN RESEARCH
      VARIABLES: Mood, worry, relationships with significant others, loneliness, and
      symptoms. FINDINGS: Data analysis showed no significant differences between
      groups, and both improved on some of the outcomes. Significant time-by-location
      interaction effects were found when comparing the Arkansas and New Jersey
      samples, thereby supporting the need to consider regional differences when
      developing interventions. CONCLUSIONS: The mailed educational resource kit alone
      appeared to be as effective as the telephone social support provided by oncology
      nurses in conjunction with the mailed resource kit. IMPLICATIONS FOR NURSING:
      Mailed educational resource kits may be the most efficient and cost-effective way
      to provide educational support to newly diagnosed patients with breast cancer,
      but their effect may differ according to region.

PMID- 15990912
TI  - Training pain resource nurses: changes in their knowledge and attitudes.
AB  - PURPOSE/OBJECTIVES: To determine the changes in knowledge and attitudes of pain
      resource nurses (PRNs) as a result of an intensive pain management course.
      DESIGN: Pre- and post-test design. SETTING: A Veterans Administration hospital in
      the southeastern United States. SAMPLE: 18 RNs from multiple units where care is
      provided for veterans with cancer. METHODS: The PRNs were tested before and after
      a 32-hour intensive pain management course. MAIN RESEARCH VARIABLES: Knowledge
      about pain management, attitudes toward pain management, and attitudes toward
      patients in pain. FINDINGS: Significant improvements were found in pain knowledge
      and attitudes toward patients in pain. Improvements in attitudes toward pain
      management approached significance. CONCLUSIONS: The improvements in scores not
      only supported the effectiveness of the course but also provided additional
      evidence of the validity of the assessment instruments. IMPLICATIONS FOR NURSING:
      Courses such as this should be offered in other settings to encourage practicing
      nurses to provide better care to patients in pain and to serve as role models for
      their peers.

PMID- 15990913
TI  - Pain resource nurses: believing the patients, and believing in themselves.
AB  - PURPOSE/OBJECTIVES: To describe the experience of being a pain resource nurse
      (PRN), discuss the influence of the PRN's role on colleagues and patient care,
      and explore barriers to the PRN role. DESIGN: Qualitative, exploratory. SETTING:
      A Veterans Administration hospital in the southeastern United States. SAMPLE: 12
      nurses who received advanced training in pain assessment and management attended
      focus groups approximately one year after assuming the PRN role. METHODS: Two
      focus group sessions, each with four to eight nurses. Each nurse was asked to
      describe her experience. Interviews were transcribed verbatim. Data were analyzed
      using Spradley's domain analysis for discovering processes and themes from the
      transcribed data. MAIN RESEARCH VARIABLES: The experience of being a PRN, the
      influence of the PRN on staff and patients, and barriers to the role and pain
      management. FINDINGS: The key processes that described the PRN experience were
      Believing the Patients (i.e., an awareness that nurses must have to effectively
      manage patients' pain) and Believing in Themselves (i.e., the PRNs gained
      authority as experts in pain management, accepted the responsibility of being
      champions in pain management, and gave themselves permission to make patients
      comfortable). CONCLUSIONS: The pain-training course the PRNs received enabled
      them to practice as confident, credible, and empowered professionals. The
      awareness that they acquired during the course and the year of practice allowed
      the PRNs to be patient advocates, role models, and educators. IMPLICATIONS FOR
      NURSING: The findings of this study indicate a high level of nurse satisfaction
      with the PRN role. Nurses with an interest and specialized knowledge in pain
      assessment and management at the unit level may greatly improve patient outcomes.

PMID- 15990914
TI  - Independent nursing actions in cooperative care.
AB  - PURPOSE/OBJECTIVES: To identify and describe independent nursing actions in
      cooperative care. DESIGN: Qualitative, descriptive, inductive study. SETTING: The
      Nebraska Medical Center's Lied Transplant Center in Omaha, where lay care
      partners assume responsibility for acute care of transplant recipients in
      partnership with nurses. SAMPLE: 12 cooperative care nurses. METHODS: Two focus
      groups, 59 narrative logs, and three follow-up interviews were tape recorded,
      transcribed, and content analyzed. MAIN RESEARCH VARIABLE: Independent nursing
      actions in cooperative care. FINDINGS: Independent nursing actions included
      surveillance, teaching, coaching, fostering partnerships, providing psychosocial
      support, rescuing, and coordinating. Surveillance leads to problem identification
      that, in turn, triggers other actions. Because all nursing actions occur in the
      context of nurse, dyad, and healthcare team relationships, coordinating is the
      category of nursing action used to manage all aspects of care. CONCLUSIONS: The
      nurses integrated specialized knowledge and expertise while dynamically using
      surveillance to identify problems that trigger nursing actions to manage signs
      and symptoms. Cooperative care is an example of apprenticeship or guided
      participation in which a community of experts (nurses) guides, supports, and
      challenges novices (lay individuals) to participate in skilled activities until
      the responsibility for the activities can be transferred to the novice.
      IMPLICATIONS FOR NURSING: Independent nursing actions identified in this study
      are the first step in formulating an instrument to measure "doses" (frequency and
      intensity) of nursing actions in cooperative care. Such an instrument is needed
      to evaluate interventions designed to prepare and support lay care partners.

PMID- 15990915
TI  - Teaching breast cancer screening to African American women in the Arkansas
      Mississippi river delta.
AB  - PURPOSE/OBJECTIVES: To determine the effectiveness of a multifaceted, culturally
      sensitive breast cancer education program for African American women in the
      Arkansas Mississippi River Delta. DESIGN: Experimental (i.e., posttest only,
      control group design). SETTING: African American churches and a county Extension
      Homemakers Club sponsored through the Arkansas Extension Homemakers council.
      SAMPLE: 53 African American women. The experimental group included 30
      participants who had a mean age of 56 years, and the control group consisted of
      23 participants with a mean age of 51 years. METHODS: After the presentation of a
      multifaceted, culturally sensitive breast cancer education program, a variety of
      instruments were administered to participants in the experimental group that
      measured dependent variables. Subjects in the control group completed the same
      instruments in the absence of a viable intervention. Data were analyzed using t
      tests. MAIN RESEARCH VARIABLES: Knowledge and beliefs about breast cancer.
      FINDINGS: The experimental group's mean scores were significantly higher than the
      control group's on the Breast Cancer Knowledge Test and the susceptibility scale
      of the Breast Cancer Screening Belief Scales. The experimental group also scored
      significantly higher than the control group on the confidence scale of the Breast
      Cancer Screening Belief Scales. CONCLUSIONS: The multifaceted, culturally
      sensitive breast cancer education program appeared to be responsible for the
      differences in scores between the experimental and control groups. IMPLICATIONS
      FOR NURSING: Culturally sensitive group educational programs aimed at helping
      African American women in the rural South become more knowledgeable about breast
      cancer and early detection clearly are needed. Such efforts also must focus on
      increasing women's confidence in effectively performing regular breast self
      examination as well as their understanding of personal risk. Healthcare
      professionals play a major role in the development and implementation of these
      programs.

PMID- 15990916
TI  - Design of vascular endothelium-specific drug-targeting strategies for the
      treatment of cancer.
AB  - Tumor endothelial cells are actively involved in the neovascularization processes
      that accompany tumor growth. Their easy accessibility for systemically applied
      therapeutics makes them interesting targets for therapeutic intervention.
      Especially for drug targeting-based therapeutics that often consist of
      macromolecular moieties, the tumor endothelium is considered a much better target
      than the tumor cells located behind the vascular wall barrier. In this review,
      the general principles underlying the development and choices in the development
      of vascular drug-targeting strategies are discussed. An overview of target
      epitopes identified in the past two decades is followed by a summary of those
      strategies that directly or indirectly induced tumor blood flow blockade in vivo.
      The demonstrated therapeutic success in pre-clinical animal models in debulking
      large tumor masses and inhibiting tumor outgrowth warrant further development of
      these therapeutic approaches. Yet, more effort should be put in studies in which
      the efficacy of different effector activities aimed at the same target, of one
      effector activity aimed at different targets, and of multiple target strategies
      are be compared. Combining these data with proper inventories on the molecular
      basis of tumor endothelial heterogeneity in general will make possible the
      development of tumor vascular drug-targeting strategies towards clinical
      application.

PMID- 15990917
TI  - Prospects for p53-based cancer therapy.
AB  - The p53 tumor suppressor plays the role of a cellular hub which gathers stress
      signals such as damage to DNA or hypoxia and translates them into a complex
      response. p53 exerts its action mainly as a potent transcription factor. The two
      major outcomes of p53 activity are highlighted: cell cycle arrest and apoptosis.
      During malignant transformation p53 or p53-pathway related molecules are disabled
      extremely often. Mutations in p53 gene are present in every second human tumor. A
      mutant form of p53 may not only negate the wild type p53 function but may play
      additional role in tumor progression. Therefore p53 represents a relatively
      unique and specific target for anticancer drug design. Current approaches include
      several different molecules able to restore p53 wild-type conformation and
      activity. Such small molecule drugs hold great promise in treating human tumors
      with dysfunction of p53 pathway in the near future.

PMID- 15990918
TI  - TGF beta signalling and its role in tumour pathogenesis.
AB  - Transforming growth factor beta (TGF-beta) is a multifunctional cytokine involved
      in the regulation of cell proliferation, differentiation and survival/or
      apoptosis of many cells. Knock-out experiments in mice for the three isoforms of
      TGF-beta have demonstrated their importance in regulating inflammation and tissue
      repair. TGF-beta is implicated in the pathogenesis of human diseases, including
      tissue fibrosis and carcinogenesis. TGF-beta receptors act through multiple
      intracellular pathways. Upon binding of TGF-beta with its receptor, receptor
      regulated Smad2/3 proteins become phosphorylated and associate with Smad4. Such
      complex translocates to the nucleus, binds to DNA and regulates transcription of
      specific genes. Negative regulation of TGF-beta/Smad signalling may occur through
      the inhibitory Smad6/7. Furthermore, TGF-beta-activated kinase-1 (TAK1) is a
      component of TGF-beta signalling and activates stress-activated kinases: p38
      through MKK6 or MKK3 and c-Jun N-terminal kinases (JNKs) via MKK4. In the brain
      TGF-beta, normally expressed at the very low level, increases dramatically after
      injury. Increased mRNA levels of the three TGF-beta isoforms correlate with the
      degree of malignancy of human gliomas. TGF-betas are secreted as latent
      precursors requiring activation into the mature form. TGF-beta may contribute to
      tumour pathogenesis by direct support of tumour growth and influence on local
      microenvironment, resulting in immunosuppression, induction of angiogenesis, and
      modification of the extracellular matrix. TGF-beta1,2 may stimulate production of
      vascular endothelial growth factor (VEGF) as well as plasminogen activator
      inhibitor (PAI-I), that are involved in vascular remodelling occurring during
      angiogenesis. Blocking of TGF-beta action inhibits tumour viability, migration,
      metastases in mammary cancer, melanoma and prostate cancer model. Reduction of
      TGF-beta production and activity may be a promising target of therapeutic
      strategies to control tumour growth.

PMID- 15990919
TI  - Direct tumor damage mechanisms of photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a clinically approved and rapidly developing cancer
      treatment regimen. It is a minimally invasive two-stage procedure that requires
      administration of a photosensitizing agent followed by illumination of the tumor
      with visible light usually generated by laser sources. A third component of PDT
      is molecular oxygen which is required for the most effective antitumor effects.
      In the presence of the latter, light of an appropriate wavelength excites the
      photosensitizer thereby producing cytotoxic intermediates that damage cellular
      structures. PDT has been approved in many countries for the treatment of lung,
      esophageal, bladder, skin and head and neck cancers. The antitumor effects of
      this treatment result from the combination of direct tumor cell photodamage,
      destruction of tumor vasculature and activation of an immune response. The
      mechanisms of the direct photodamage of tumor cells, the signaling pathways that
      lead to apoptosis or survival of sublethaly damaged cells, and potential novel
      strategies of improving the antitumor efficacy of PDT are discussed.

PMID- 15990920
TI  - Stem cell biology: a never ending quest for understanding.
AB  - Stem cells (SC) research is an important part of biotechnology that could lead to
      the development of new therapeutic strategies. A lot of effort has been put to
      understand biology of the stem cells and to find genes and subsequently proteins
      that are responsible for their proliferation, self-renewal and differentiation.
      Different cytokines and growth factors has been used to expand stem cells, but no
      combination of these factors was identified that could effectively expand the
      most primitive stem cells. Recently, however, genes and receptors responsible for
      SC proliferation and differentiation have been described. Ligands for these
      receptors or these genes themselves are being already used for ex vivo expansion
      of stem cells and the first data are very promising. New markers, such as CXCR4
      and CD133, have been discovered and shown to be present on surface of
      hematopoietic stem cells. The same markers were recently also found to be
      expressed on neuronal-, hepatic- or skeletal muscle-stem cells. By employing
      these markers several laboratories are trying to isolate stem cells for potential
      clinical use. New characteristics of stem cells such as transdifferentiation and
      cell fusion have been described. Our team has identified a population of tissue
      committed stem cells (TCSC). These cells are present in a bone marrow and in
      other tissues and they can differentiate into several cell types including
      cardiac, neural and liver cells.

PMID- 15990921
TI  - Genetic models to study adult neurogenesis.
AB  - In the central nervous system (CNS) generation of new neurons continues
      throughout adulthood, when it is limited to the olfactory bulb and hippocampus.
      The knowledge regarding the function of newly-generated neurons remains limited
      and is vigorously investigated using diverse approaches. Among these are
      genetically modified mice, most of them of knock-out type (KO). Results from 23
      diverse KO mouse models demonstrate the importance of particular proteins (growth
      factors, nitric oxide synthases, receptors, cyclins/cyclin-associated proteins,
      transcription factors, etc.) in adult neurogenesis (ANGE) as well as separate it
      from developmental neurogenesis. These results bring us closer to revealing the
      function of newly generated neurons in adult brains.

PMID- 15990922
TI  - Circular dichroism and aggregation studies of amyloid beta (11-8) fragment and
      its variants.
AB  - Aggregation of Abeta peptides is a seminal event in Alzheimer's disease. Detailed
      understanding of Abeta assembly would facilitate the targeting and design of
      fibrillogenesis inhibitors. Here comparative conformational and aggregation
      studies using CD spectroscopy and thioflavine T fluorescence assay are presented.
      As a model peptide, the 11-28 fragment of Abeta was used. This model peptide is
      known to contain the core region responsible for Abeta aggregation. The
      structural and aggregational behaviour of the peptide was compared with the
      properties of its variants corresponding to natural, clinically relevant mutants
      at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). In HFIP (hexafluoro-2
      propanol), a strong alpha-helix inducer, the CD spectra revealed an unexpectedly
      high amount of beta-sheet conformation. The aggregation process of Abeta(11-28)
      variants provoked by water addition to HFIP was found to be consistent with a
      model of an alpha-helix-containing intermediate. The aggregation propensity of
      all Abeta(11-28) variants was also compared and discussed.

PMID- 15990923
TI  - Splenic eumelanin differs from hair eumelanin in C57BL/6 mice.
AB  - The presence of melanin in spleens of black C57BL/6 mice has been known for long.
      Although its origin and biological functions are still obscure, the relation of
      splenic melanin to the hair follicle and skin pigmentation was suggested. Here,
      we demonstrated using for the first time electron paramagnetic resonance
      spectroscopy that black-spotted C57BL/6 spleens contain eumelanin. Its presence
      here is a "yes or no" phenomenon, as even in the groups which revealed the
      highest percentage of spots single organs completely devoid of the pigment were
      found. Percentage of the spotted spleens decreased, however, with the progress of
      telogen after spontaneously-induced hair growth. The paramagnetic properties of
      the spleen eumelanin differed from the hair shaft or anagen VI skin melanin. The
      splenic melanin revealed narrower signal, and its microwave power saturability
      betrayed more heterogenous population of paramagnetic centres than in the skin or
      hair shaft pigment. Interestingly, the pigment of dry hair shafts and of the wet
      tissue of depilated anagen VI skin revealed almost identical properties. The
      properties of splenic melanin better resembled the synthetic dopa melanin (water
      suspension, and to a lesser degree -- powder sample) than the skin/hair melanin.
      All these findings may indicate a limited degradation of splenic melanin as
      compared to the skin/hair pigment. The splenic eumelanin may at least in part
      originate from the skin melanin phagocyted in catagen by the Langerhans cells or
      macrophages and transported to the organ.

PMID- 15990924
TI  - The involvement of oxidative stress in determining the severity and progress of
      pathological processes in dystrophin-deficient muscles.
AB  - In both forms of muscular dystrophy, the severe Duchenne's muscular dystrophy
      (DMD) with lifespan shortened to about 20 years and the milder Becker dystrophy
      (BDM) with normal lifespan, the gene defect is located at chromosome locus Xp21.
      The location is the same in the experimental model of DMD in the mdx mice. As the
      result of the gene defect a protein called dystrophin is either not synthesized,
      or is produced in traces. Although the structure of this protein is rather well
      established there are still many controversies about the dystrophin function. The
      most accepted suggestion supposes that it stabilizes sarcolemma in the course of
      the contraction-relaxation cycle. Solving the problem of dystrophin function is a
      prerequisite for introduction of an effective therapy. Among the different
      factors which might be responsible for the appearance and progress of dystrophic
      changes in muscles there is an excessive action of oxidative stress. In this
      review data indicating the influence of oxidative stress on the severity of the
      pathologic processes in dystrophy are discussed. Several pieces of data
      indicating the action of oxidative damage to different macromolecules in DMD/BDM
      are presented. Special attention is devoted to the degree of oxidative damage to
      muscle proteins, the activity of neuronal nitric oxide synthase (nNOS) and their
      involvement in defining the severity of the dystrophic processes. It is indicated
      that the severity of the morbid process is related to the degree of oxidative
      damage to muscle proteins and the decrease of the nNOS activity in muscles.
      Estimation of the degree of the destructive action of oxidative stress in
      muscular dystrophy may be a useful marker facilitating introduction of an
      effective antioxidant therapy and regulation of nNOS activity.

PMID- 15990925
TI  - Ultrastructure of diaphragm from dystrophic alpha-sarcoglycan-null mice.
AB  - alpha-Sarcoglycan is a 50 kDa single-pass transmembrane glycoprotein exclusively
      expressed in striated muscle that, together with beta-, gamma-, and delta
      sarcoglycan, forms a sub-complex at the muscle fibre cell membrane. The
      sarcoglycans are components of the dystrophin-associated glycoprotein (DAG)
      complex which forms a mechanical link between the intracellular cytoskeleton and
      extracellular matrix. The DAG complex function is to protect the muscle membrane
      from the stress of contractile activity and as a structure for the docking of
      signalling proteins. Genetic defects of DAG components cause muscular
      dystrophies. A lack or defects of alpha-sarcoglycan causes the severe type 2D
      limb girdle muscular dystrophy. alpha-Sarcoglycan-null (Sgca-null) mice develop
      progressive muscular dystrophy similar to the human disorder. This animal model
      was used in the present work for an ultrastructural study of diaphragm muscle.
      Diaphragm from Sgca-null mouse presents a clear dystrophic phenotype, with
      necrosis, regeneration, fibre hypertrophy and splitting, excess of collagen and
      fatty infiltration. Some abnormalities were also observed, such as centrally
      located nuclei of abnormal shape, fibres containing inclusion bodies within the
      contractile structure, and fibres with electron-dense material dispersed over
      almost the entire cell. Additionally, unusual interstitial cells of uncertain
      identity were detected within muscle fibres. The abnormal ultrastructure of the
      diaphragm from Sgca-null mice is discussed.

PMID- 15990926
TI  - A 2D-IR study of heat- and [(13)C]urea-induced denaturation of sarcoplasmic
      reticulum Ca(2+)-ATPase.
AB  - Two-dimensional infrared correlation spectroscopy (2D-IR) was applied to the
      study of urea- and heat-induced unfolding denaturation of sarcoplasmic reticulum
      Ca(2+)-ATPase (SR ATPase). Urea at 2-3 M causes reversible loss of SR ATPase
      activity, while higher concentrations induce irreversible denaturation. Heat
      induced denaturation is a non-two-state process, with an "intermediate state" (at
      t approximately 45 degrees C) characterized by the presence of protein monomers,
      instead of the native oligomers. 2D-IR reveals that urea denaturation causes loss
      of the structural transition to the "intermediate state". Whenever the urea
      effect can be reversed, the transition to the "intermediate state" is re
      established.

PMID- 15990927
TI  - The level of endogenous DNA damage in lymphocytes isolated from blood is
      associated with the fluctuation of 17beta-estradiol concentration in the
      follicular phase of healthy young women.
AB  - The aim of this study was to evaluate whether the differences in plasma 17beta
      estradiol concentration in early and late follicular phases of the menstrual
      cycle can affect the level of endogenous DNA damage in lymphocytes assessed by
      comet assay, and whether the extent of this damage in the follicular phase is
      associated with the genotype of catechol-O-methyltransferase (COMT). The level of
      DNA damage was positively correlated with 17beta-estradiol concentration only in
      the late follicular phase. Subjects with the COMT L/L homozygous mutated variant
      revealed more DNA damage as compared to individuals with the COMT wild-type and
      heterozygous (H/L+HH) genotype.

PMID- 15990928
TI  - Effectiveness and tolerability of pegylated Interferon alpha-2a and ribavirin
      combination therapy in Romanian patients with chronic hepatitis C: from clinical
      trials to clinical practice.
AB  - BACKGROUND AND AIM: Pegylated interferon alpha in combination with ribavirin
      represents nowadays the gold standard therapy in patients with chronic hepatitis
      C. The aim of this study was to assess early (EVR) and sustained virological
      response (SVR), tolerability and baseline predictive factors for SVR in patients
      with chronic hepatitis C treated with peginterferon alpha-2a and ribavirin
      combination therapy in day-to-day clinical practice. METHODS: The analysis
      included 174 consecutive patients with chronic hepatitis C (naive, relapsers and
      non-responders after standard therapy) managed in two expertise gastroenterology
      centers in Romania, mainly on an outpatient basis. The combination therapy was
      initiated between 1st of June 2002 - 30th of June 2003. RESULTS: The mean age of
      the study population was 47 years; 41% were men, mean BMI was 26.5 kg/sq.m. Only
      7.5% of them had bridging fibrosis/cirrhosis on liver biopsy. EVR and SVR were
      noted in 78.7% and 51.1%, respectively. Multivariate analysis showed two
      independent variables associated with SVR: absence of bridging fibrosis/cirrhosis
      and absence of hepatic steatosis. The rate and profile of side effects associated
      with pegylated interferon alpha-2a and ribavirin in our clinical setting were all
      predictable, based on previous experience in the literature. Side effects
      resulted in interferon and ribavirin dose reductions in 9.2% and, respectively,
      25.3%, but permanent discontinuation of the combination therapy was required in
      only 5.74% of patients. CONCLUSION: Combination antiviral therapy can be safely
      and successfully used outside clinical trials. To achieve high response rates and
      tolerability, similar or better than those reported in clinical trials, hepatitis
      C patients have to be managed in expertise centers, by experienced physicians,
      aiming at minimizing side effects, optimizing dosing, and enhancing compliance.

PMID- 15990929
TI  - Relationship between obesity and gastroesophageal reflux disease as recorded by 3
      hour esophageal pH monitoring.
AB  - OBJECTIVE: To evaluate the presence of gastroesophageal reflux disease (GERD) in
      a Greek cohort in relationship to the body mass index (BMI), using the 3-hr
      postprandial esophageal pH monitoring. METHODS: Sixty-four consecutive patients
      (55 males, 9 females; mean age 40.7 +/- 13.7 years) with at least weekly attacks
      of heartburn or acid regurgitation for a period longer than one year, were
      screened endoscopically for esophagitis and underwent a 3-hr postprandial pH
      monitoring to quantify the reflux. DeMeester score was calculated. The patients
      were allocated to three groups: group A (reference group, n=23) with BMI < 25
      kg/m(2) (normal); group B (n=25) with BMI 25-30 kg/m(2) (overweight), and group C
      (n=16) with BMI > 30 kg/m(2) (obese). RESULTS: A higher DeMeester score, as well
      as a decreased lower esophageal sphincter pressure were evidenced with increasing
      BMI. Moreover, there was an association between increasing BMI and the point
      scale of reflux symptoms. The number of cases with severe reflux symptoms
      increased significantly among overweight (odds ratio: 4.94, 95%CI: 0.95-25.56)
      and obese (odds ratio: 8.18, 95%CI: 1.19-56.00) patients. CONCLUSIONS: The
      shorter 3-hr postprandial test appears to be diagnostic for GERD and acceptable
      by patients, reducing discomfort and enhancing compliance. Our study confirms the
      link between obesity and GERD. BMI is strongly associated with the point scale of
      reflux symptoms both in overweight and obese patients.

PMID- 15990930
TI  - The effect of a combined treatment with propranolol and isosorbide-5-mononitrate
      on Doppler ultrasound parameters in patients with cirrhosis and portal
      hypertension.
AB  - OBJECTIVES: The objectives of this study were to compare the effect of the
      treatment with propranolol to that with propranolol and isosorbide-5-mononitrate
      in portal hypertension, as assessed by Doppler ultrasound parameters in patients
      with cirrhosis. METHODS: A prospective study of two groups, each of 30 patients
      with cirrhosis Child-Pugh A was performed. In one group 40 mg/day propranolol
      were administered for 6 months and in the other, a combined treatment with
      propranolol 40 mg/day and isosorbide-5-mononitrate 40 mg/day was administered for
      6 months. In all patients the presence of esophageal varices was confirmed by
      upper gastrointestinal endoscopy and abdominal ultrasonography and Doppler
      ultrasonography of the portal vein was performed. The patients were monitored
      for: the velocity of blood flow in the portal vein, the cross sectional area of
      the portal vein and the portal vein congestion index. Data analysis used t
      Student test, Pearson and Spearman correlation. A p value of <0.05 was considered
      to be significant. RESULTS: A significant decrease of all parameters after 6
      months was observed in the group with combined therapy with propranolol and
      isosorbide-5-mononitrate (p<0.05). The relative decrease of the cross sectional
      area of the portal vein and of the portal vein congestion index was more
      important when patients had higher initial values of the two parameters,
      indicating an increased hemodynamic impairment (Pearson, p<0.001). In patients
      treated only with propranolol, the relative decrease correlated with its initial
      value for all parameters. CONCLUSION: The combined therapy with propranolol and
      isosorbide-5-mononitrate proved to be superior to the mono-therapy with
      propranolol in decreasing the hemodynamic parameters in portal hypertension,
      probably by an additive effect.

PMID- 15990931
TI  - Predictive factors for pseudocysts and peripancreatic collections in acute
      pancreatitis.
AB  - BACKGROUND: Acute pancreatitis (AP) is a proteiform disease which may lead to
      various complications. Pancreatic pseudocysts and fluid collections are among the
      most frequent of them. The aim of our study was to find predictive factors of
      their occurrence. METHODS: We carried out a retrospective cohort study comprising
      one year patients admitted to our department with AP. Fisher's exact and U Mann
      Whitney tests were used for correlations, with a probability of error < 5%
      (p<0.05). RESULTS: We included 62 patients with a mean age of 49 years; 77.4%
      were males. AP etiology was due to alcohol (58.1%), biliary disorders (22.6%),
      hyper-triglycerides (8.1%) and post-ERCP (3.2%). Pancreatic cancer was revealed
      in (6.5%) patients. From the whole group 2 patients (3.2%) died. There were 22
      patients with pseudocysts (35.5%) and 13 patients with acute fluid collections
      (21%). Multiple pseudocysts were present in 12 cases (54.5%), mean diameter was
      39.5 mm. Pancreatic head localization was most frequent (63.6%). Alcoholic
      etiology was associated with acute pseudocysts formation (p=0.007) as well as
      lower values of alkaline phosphatase (96 U/L versus 286 U/L, p = 0.016). The area
      under the receiver operating characteristics curve demonstrated values of
      alkaline phosphatase < 2 x upper normal values were predicting pseudocyst
      occurrence with > 90% specificity. Presence of ascites predicted formation of
      acute fluid collections, (p < 0.001). CONCLUSIONS: Alcoholic etiology and low
      values of serum alkaline phosphatase seem to predict pseudocysts formation in
      acute pancreatitis, while ascites forecast acute fluid collections occurrence.

PMID- 15990933
TI  - Surveillance of patients with chronic hepatitis C not on antiviral therapy: a
      practical approach.
AB  - Surveillance of patients with HCV-related chronic liver disease (CHC) not on
      antiviral therapy is mandatory, because of the risk of worsening of the disease
      and progression to cirrhosis and its lethal complications. Unfortunately, data
      from the literature are scarce, and sometimes there are differences among experts
      and discrepancies between recommendations. Furthermore, the wide range of
      diagnostic tests and the continuous development of new diagnostic tools not
      rarely results in expensive, redundant and not justified surveillance programs.
      The identification of the optimal frequency of follow-ups constitutes another
      source of difficulties for the physicians. The purpose of this article is to
      provide practicing physicians with published criteria for performing a cost
      effective and adequate surveillance program for patients with CHC not on
      antiviral treatment. On the basis of randomized controlled trials (RCTs),
      metanalysis, and international guide-lines and Consensus Conference statements we
      have attempted to outline a cost-effective surveillance program for HCV carriers
      with normal aminotransferases (ALT), for responders to previous interferon (IFN)
      treatment and for patients with CHC non-eligible for antiviral therapy. This
      surveillance strategy relies upon the judicious use of un-expensive and widely
      available tests.

PMID- 15990932
TI  - The Roux-en-Y procedure in congenital hepato-biliary disorders.
AB  - BACKGROUND: The use of the Roux-en-Y procedure is limited in paediatric surgery
      practice, and is performed mainly in congenital hepatobiliary disorders either as
      an initial or permanent treatment. In this 18-year retrospective study, we
      present our experience of the Roux-en-Y procedure in childhood cases of biliary
      atresia (BA) and congenital choledochal cyst (CCC). METHODS: Twenty-eight
      children (18 females and 10 males; age 25 days-12 years) with hepatobiliary
      disorders were treated in our clinics between 1986-2004. Twenty patients suffered
      from BA (11 females, 9 males) and eight from CCC (seven females, one male). The
      surgical approach in the patients with BA (mean age 2.1 months) was Roux-en-Y
      hepatic portoenterostomy (Kasai procedure) and in the patients with CCC (mean age
      7.2 years) was cyst excision with Roux-en-Y hepaticojejunostomy. The mean follow
      up period was 9.3 years. RESULTS: The children with BA developed the follow
      postoperative complications: 12 cholangitis, 6 portal hypertension and 5 hepatic
      cirrhosis. Among the children with CCC, two presented post-operative cholangitis,
      which was treated conservatively, and one developed anastomotic stricture and
      underwent reoperative reconstruction. At the end of the follow-up period among
      the children with BA 6 had died, 3 had undergone liver transplantation, and 5
      were on a waiting list for transplantation. All children with CCC were alive
      without sequelae. CONCLUSIONS: Roux-en-Y in BA, with timely diagnosis, is
      preferred as an initial procedure, followed by liver transplantation in cases
      with no bile drainage and is the only possible reconstruction in cases of CCC
      after excision of the biliary cyst.

PMID- 15990934
TI  - Does treatment of coeliac disease require full mucosal recovery?
AB  - Glutenfree diet is recommended for all coeliacs. There are almost no data on
      effective means of monitoring coeliacs. Some consider a decrease in antibody
      titer as an indication of dietary adherence. A recent American pediatric
      guideline suggests that additional biopsies are not recommended. The UEGW group
      about adult coeliacs advises a second biopsy after one year. The required
      normalisation has not been defined. Serology does not indicate complete mucosal
      recovery and cannot substitute for follow-up biopsy. Biopsy findings may not
      always be as conclusive as is imaging in explaining persistent complaints in
      coeliacs. Treating almost daily refractory coeliacs on their way to EATL, we
      suggest mucosal recovery is the only protection against such complications,
      especially in coeliacs diagnosed above the age of 50, so-called old-age coeliacs.
      A body of published data is mandatory to see if full mucosal recovery is required
      and is achievable. In countries where gluten-free products are not easily
      available as in Eastern Europe or the Middle East, this might be extremely
      difficult for the coeliacs, their doctors and dietitians.

PMID- 15990935
TI  - Morbid obesity: a surgical perspective.
AB  - Morbid obesity is a chronic illness of multifactorial aetiology which is defined
      as Body Mass Index (BMI) greater than 40 kg/sq.m. Non-surgical treatments for
      this condition have been shown to be ineffective. Surgery is the only effective
      treatment and obtains the best long-term outcomes. Surgery is indicated when BMI
      is greater than 40, or BMI is greater than 35 with significant associated co
      morbidities. Four types of operations are currently performed: restrictive,
      malabsorptive, combined procedures (malabsorptive-restrictive) and motility
      reducing pro-cedures. With restrictive procedures (adjustable gastric banding and
      vertical banded gastroplasty), patients can expect a long-term excess weight loss
      of 44-68%; for combined procedures (Roux-en-Y gastric by-pass) this is 60-70%,
      whereas for malabsorptive procedures (bilio-pancreatic diversion with or without
      duodenal switch), this is 75-80%. Intra-gastric stimulation is the least invasive
      treatment, but induces the lowest excess weight loss (32%) in the first two years
      after the operation. Gastric banding offers the best results when balancing risks
      and benefits. All procedures are now performed laparoscopically with comparable
      results to open surgery. The overall mortality rate in specialized centers is
      less than 0.3%. Different techniques are indicated according to BMI and the
      patient's eating habits. Surgery for morbid obesity has proved to improve quality
      of life and significantly reduce associated co-morbidities.

PMID- 15990936
TI  - Pill esophagitis.
AB  - Pill esophagitis is a rare clinical diagnosis. We report a series of two patients
      who experienced ulcerative esophagitis while taking doxycycline (patient 1) and
      alendronate (patient 2). Both patients presented with retrosternal pain,
      odynophagia and dysphagia. Symptoms developed after 3 days of treatment with
      doxycycline in patient 1 and after 3 months of treatment with alendronate in
      patient 2. Endoscopy revealed ulcerative lesions in the mid-esophagus, sparing
      the distal esophagus. Biopsies showed inflammatory infiltrate (patient 1) and
      ulceration and hyperplastic cells (patient 2). Patient 1 recovered completely
      endoscopically after discontinuation of the antibiotic and a one month course of
      sucralfate treatment. Patient 2 did not accept the discontinuation of alendronate
      therapy. She also had a course of one month treatment with sucralfate. At one,
      two and even at seven months after the first diagnosis, endoscopy still showed
      the persistence of millimetric defects of epithelisation. She is still under
      endoscopical survey. In conclusion, doxycycline and alendronate can cause
      chemical esophagitis when taken improperly. In adults and elderly patients
      exclusion of esophageal carcinoma by histology is necessary. Continuation of
      treatment with the offending drug can delay healing. Pill esophagitis is a
      preventable cause of morbidity that consists of giving simple advice of how and
      when to take medication.

PMID- 15990937
TI  - Gallbladder varices.
AB  - Gallbladder varices are relatively rare ectopic varices in patients with portal
      hypertension. We present here a case of gallbladder varices accurately diagnosed
      by color Doppler sonography. A 51-year-old woman was admitted to our unit with
      recurrent esophageal varices bleeding due to extrahepatic portal vein occlusion
      after splenectomy. Bleeding was controlled by endoscopic band ligation and
      esophageal varices were eradicated after the second endoscopic session. Doppler
      imaging showed the existence of portal cavernoma and gallbladder varices. The
      close follow-up period after complete eradication of esophageal varices showed no
      enlargement of varices of the gallbladder or complications related to them. Color
      Doppler sonography is a valuable noninvasive imaging technique for assessment of
      portal hemodynamic profile in patients with portal cavernoma as well as useful in
      detecting gallbladder varices. Preoperative correct diagnosis of gallbladder
      varices should increase the surgeon's vigilance during biliary tract surgery in
      patients with portal hypertension in order to avoid hazardous complications.

PMID- 15990938
TI  - Recurrent cholangitis as the first manifestation of an intraductal papillary
      mucinous tumor of the pancreas.
AB  - Intraductal papillary mucinous tumor is a rare pancreatic tumor originating from
      the epithelium of the pancreatic duct and exhibiting papillary proliferation of
      tall columnar epithelial cells. The usual clinical presentation is recurrent
      episodes of pancreatitis due to hypersecretion of mucin and obstruction of a
      markedly dilated pancreatic duct. We describe a 74-year-old man who presented
      recurrent attacks of cholangitis, due to a common bile duct obstruction from
      thick pancreatic mucus reflux, as the first manifestation of intraductal
      papillary mucinous tumor.

PMID- 15990939
TI  - Unusual presentation of gallstones.
AB  - Gallstones are usually asymptomatic in the majority of patients. Gallstones can
      migrate through a cholecysto-duodenal fistula and may cause an intestinal
      obstruction anywhere along the gastrointestinal tract. The obstruction usually
      occurs at the level of the ileocecal valve. In most cases, the clinical
      presentation includes symptoms related to the intestinal obstruction including
      abdominal pain and vomiting. We report an unusual case of gallstones presented
      with acute prerenal azotemia as the major manifestation.

PMID- 15990940
TI  - Curative endoscopic ultrasound-assisted submucosal resection of a gastric stromal
      tumor.
AB  - Endoscopic submucosal resection has been proposed as a feasible alternative for
      the diagnosis and treatment of small submucosal tumors (< 3 cm), as compared to
      classic interventions (surgical intervention or frequent follow-up). Therapeutic
      options should be established after precise endoscopic ultrasound assessment of
      the tumor characteristics. We present the case of a 60 year-old patient, admitted
      to the Emergency Department for upper gastrointestinal (GI) bleeding. Upper GI
      endoscopy showed a submucosal tumor on the posterior gastric wall, with hyperemic
      covering mucosa, without central ulceration. Endoscopic ultrasound identified a
      10-mm well-delimited hypoechoic lesion, with the origin in the third hyperechoic
      layer (submucosa). After injection of 1:10000 epinephrine in the submucosa, with
      subsequent elevation of the protrusive formation, we performed an endoscopic
      submucosal resection without any complications. Pathology exam showed a gastric
      stromal tumor with low mitotic activity, the endoscopic resection being
      considered curative. The absence of independent risk factors determined by
      ultrasound endoscopy (size > 3 cm, irregular margins, hyperechoic foci > 3 mm,
      cystic spaces > 4 mm, presence of intratumoral Doppler signal), as well as the
      low mitotic activity, permitted the subsequent follow-up of the patient. A
      control endoscopic examination performed after 4 weeks showed the healing of the
      post-resection ulceration. In conclusion, ultrasound endoscopy allowed the
      establishment of a correct presumptive diagnosis and the subsequent assistance of
      endoscopic submucosal resection, used for pathological confirmation and for
      curative endoscopic treatment.

PMID- 15990941
TI  - Contribution of ultrasound to the diagnosis of chronic pancreatitis and to
      evaluating its main complications.
AB  - Chronic pancreatitis is a disease with a potentially severe evolution due to the
      pain altering life quality and to the possibility of causing exocrine and
      endocrine pancreatic insufficiency. Ultrasound represents the main imaging
      technique to be used in this disease since the identification of pancreatic
      calcifications has diagnostic significance. Endoscopic ultrasound may sometimes
      identify parenchymal changes facilitating diagnosis in the early stages of
      chronic pancreatitis when transabdominal ultrasound and endoscopic retrograde
      cholangiopancreatography show normal situations or non-characteristic changes.

PMID- 15990942
TI  - Sedation during colonoscopy.
AB  - In order to perform a proper screening for colonic cancer, repeated colonoscopies
      are required. Comfort during colonoscopy is very important, so that the patient
      will accept repeated procedures. Currently, there are 3 types of sedation used
      during colonoscopy: general anesthesia performed by an anesthesiologist; sedo
      analgesia performed by an anesthesiologist or by a gastroenterologist; sedo
      analgesia performed by a trained nurse. Sedo-analgesia is the most frequently
      used type of sedation during colonoscopy worldwide. It is realized by combining
      midazolam with propofol and/or fentanyl (alfentanyl) or pethidine. According to
      the data obtained from 34 centers performing colonoscopy in Romania, in 2003,
      22,162 colonoscopies were performed: 54.5% without anesthesia, 39.5% with
      sedation with midazolam and 6% with sedo-analgesia. In a study performed in our
      department we noticed a significant improvement in the outcome of the colonoscopy
      when sedo-analgesia was used on a regular basis. The percentage of total
      colonoscopies (excluding those that could not be continued due to stenosis) was
      84.2% when sedation was seldomly performed and 92.3% when sedo-analgesia was
      regularly used (p=0.042). We believe that the strategy of sedation during
      colonoscopy in Romania should be changed so that all the patients should benefit
      from sedo-analgesia, proved to be safe and cost/efficient.

PMID- 15990943
TI  - PPIs for upper digestive symptoms: EBM does not support empirical practice.

PMID- 15990946
TI  - Functional characterization of brain mitochondrial nitric oxide synthase during
      hypertension and aging.
AB  - Nitric oxide (NO*) plays an important role in various physiological processes.
      The aim of the present study was to investigate if brain mitochondrial nitric
      oxide synthase (mtNOS) is active and functional during hypertension. L-citrulline
      production, an indicator of nitric oxide synthesis, was concentration-dependent
      on L-arginine in all strains and all ages tested, and was inhibited by 7
      Nitroindazole (7-NI). Brain mitochondria of 1 month-old (prehypertensive)
      spontaneously hypertensive rats (SHR) exhibited a significantly (p < 0.05) low
      basal L-citrulline content as compared to age-matched Wistar (W) and Wistar-Kyoto
      (WKY) rats. L-citrulline synthesis in SHR rats showed a significant (p < 0.01)
      low response to L-arginine in 3 and 7 months-old rats. Respiratory rates in
      states 3 and 4 increased with low L-arginine concentration in all strains and all
      ages. The results suggest that in rat brain mitochondria, L-citrulline synthesis
      is constant once age-related hypertension is installed and NO* does not regulate
      oxidative phosphorylation.

PMID- 15990947
TI  - Reaction of pyridoxamine with malondialdehyde: mechanism of inhibition of
      formation of advanced lipoxidation end-products.
AB  - Advanced glycation end products (AGEs) and advanced lipoxidation end products
      (ALEs) are implicated in many age-related chronic diseases and in protein aging.
      Recent studies suggest that pyridoxamine (PM) is an efficient AGEs/ALEs inhibitor
      in various biological systems. Because malondialdehyde (MDA) is an important
      intermediate in the formation of ALEs during lipid peroxidation, the purpose of
      this study is to determine whether PM can trap MDA directly and thereby prevent
      ALEs formation. PM reacted readily with MDA under physiological conditions.
      Within 6 h, a 1-pyridoxamino-propenal adduct derived from reaction of equimolar
      PM + MDA was detected. A 1-amino-3-iminopropene complex and a dihydropyridine
      pyridinium complex were also identified after 7 d incubation. PM also greatly
      inhibited the lipofuscin-like fluorescence formation induced by MDA reaction with
      bovine serum albumin (BSA). Our results showed clearly that PM inhibited the
      formation of ALEs by trapping MDA directly under physiological condition, and
      provide insight into the mechanism of action of PM in protecting proteins against
      carbonyl stress.

PMID- 15990948
TI  - Laser acupuncture induced specific cerebral cortical and subcortical activations
      in humans.
AB  - As recent studies demonstrated, acupuncture can elicit activity in specific brain
      areas. This study aims to explore further the central effect using laser
      acupuncture. We investigated the cerebral effects of laser acupuncture at both
      acupoints GB43 with functional magnetic resonance imaging (fMRI). As a control
      condition the laser was mounted at the same acupoints but without application of
      laser stimulation. The group results showed significant brain activations within
      the thalamus, nucleus subthalamicus, nucleus ruber, the brainstem, and the
      Brodmann areas 40 and 22 for the acupuncture condition. No significant brain
      activations were observed within the placebo condition. The activations we
      observed were laser acupuncture-specific and predominantly ipsilateral. This
      supports the assumption that acupuncture is mediated by meridians, since
      meridians do not cross to the other side. Furthermore, we could show that laser
      acupuncture allows one to design a pure placebo condition.

PMID- 15990950
TI  - Isolated left-sided scimitar vein connecting all left pulmonary veins to the
      right inferior vena cava.
AB  - When the common pulmonary vein fails to develop, the embryonic connections of the
      pulmonary veins to one or more of the systemic veins almost always persist.
      Anomalous pulmonary venous connections to the inferior vena cava (IVC) are
      typically characterized by hypoplasia of the involved pulmonary veins and
      pulmonary artery, as well as abnormal parenchyma of the involved lung. Such cases
      have been described as "scimitar syndrome." We report the case of a young female
      patient in whom all the left pulmonary veins converged into a common vessel that
      drained into the IVC but who had a normal left pulmonary artery and left lung.
      Surgical intervention was successful, and our patient is still alive.

PMID- 15990949
TI  - Do hip protectors decrease the risk of hip fracture in institutional and
      community-dwelling elderly? A systematic review and meta-analysis of randomized
      controlled trials.
AB  - Hip fractures are an important cause of morbidity and mortality in the elderly.
      Hip protectors are padded undergarments designed to decrease the impact of a fall
      on the hip. We systematically reviewed randomized controlled trials of hip
      protectors to determine if they reduce hip fractures in the elderly. Analyses
      were pooled according to participant residence--community or institutional (the
      latter, included nursing homes, residential group homes or seniors' hostels). We
      included individually randomized and statistically adjusted cluster randomized
      trials. Seven trials of 12- to 28-month duration were included. The Safehip brand
      of hip protector was used in most studies. Compliance rates in the treatment
      groups varied from 31 to 68%. In four trials including a total of 5,696 community
      dwelling seniors, the hip fracture rates in control groups ranged from 1.1 to
      7.4%, and the pooled risk difference with hip protector allocation was 0% [95%
      confidence intervals (CI), -1%, +1%), with a relative risk of 1.07 (0.81, 1.42).
      In three trials including 1,188 institutionalized elderly participants, hip
      fracture rates in the control groups varied from 8 to 19.4%, and the pooled risk
      difference for sustaining one or more hip fractures with hip protector allocation
      was -3.7% (95% CI, -7.4%, 0.1%), with a relative risk of 0.56 (0.31, 1.01) (with
      statistically significant heterogeneity of treatment effect). In a post-hoc
      subgroup analysis of two trials comprised of exclusively nursing home residents,
      the risk difference with hip protector allocation was -4.4% (-8.09, -0.76) with a
      relative risk of 0.50 (0.28, 0.91) (n=1,014). Thus, there is little evidence to
      support the use of hip protectors outside the nursing home setting. The potential
      benefit of hip protectors in reducing hip fractures in nursing home residents
      requires further confirmation.

PMID- 15990951
TI  - Steroid therapy and cardiac function in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy leads to progressive deterioration in skeletal and
      cardiac muscle function. Steroids prolong ambulation and improve respiratory
      muscle strength. The authors hypothesized that steroid treatment would stabilize
      cardiac muscle function. Echocardiograms performed from 1997 to 2004 for 111
      subjects 21 years of age or younger with Duchenne muscular dystrophy were
      restrospectively reviewed. The medical record was reviewed for steroid treatment.
      Untreated and steroids-treated subjects did not differ in age, height, weight,
      body mass index, systolic and diastolic blood pressure, or left ventricular mass.
      The shortening fraction was lower in the untreated group. Of those treated, 29
      received prednisone and 19 received deflazacort. There was no difference in the
      shortening fraction between the two treated subgroups. Treated subjects not
      receiving steroids still had a normal shortening fraction, which was no different
      from the shortening fraction of those still receiving treatment. As compared with
      the treated subjects, the untreated subjects 10 years of age or younger were 4.4
      times more likely to have a shortening fraction less than< 28% (p = 0.03), and
      the untreated subjects older than 10 years were 15.2 times more likely to have a
      shortening fraction less than< 28% (p < 0.01). This retrospective study suggests
      that the progressive decline in cardiac function of patients with Duchenne
      muscular dystrophy can be altered by steroid treatment. The effect appears to be
      sustained beyond the duration of treatment and independent of steroid type.

PMID- 15990952
TI  - Elastin mutation screening in a group of patients affected by vascular
      abnormalities.
AB  - Supravalvular aortic stenosis is an uncommon but well-characterized congenital
      form of left ventricular outflow obstruction. The lesion involves the ascending
      aorta and often occurs in association with pulmonary arterial stenoses or
      stenoses of other arteries, especially at major branch points. It can occur
      sporadically, as an autosomal dominant condition, or as one component of Williams
      Beuren syndrome. In fact, the clinical and structural characteristics of
      supravalvular aortic stenosis are identical in both syndromic and nonsyndromic
      cases. The severity of supravalvular aortic stenosis varies; but if it is left
      untreated, it may result in heart failure, myocardial infarction, and sudden
      death. Supravalvular aortic stenosis in Williams-Beuren patients occurs as a
      consequence of a complete deletion of one copy of the elastin gene on chromosome
      7q11.23. However, the underlying genetic cause of isolated supravalvular aortic
      stenosis has been identified as translations, gross intragenic deletions, and
      point mutations that disrupt the elastin gene. We report the results obtained in
      a mutation screening of the elastin gene in 28 patients with supravalvular aortic
      stenosis and other vascular abnormalities. The aim of the screening was to
      characterize the molecular cause of this lesion. We have detected 11 changes,
      including nine polymorphisms and two novel putative missense mutations.

PMID- 15990953
TI  - Stent implantation for recurrent interatrial obstruction in an infant with
      hypoplastic left heart syndrome.
AB  - We report the case of a 19-month-old girl with hypoplastic left heart syndrome
      who, after Norwood stage 1 and 2 procedures, developed recurrent interatrial
      obstruction and was treated effectively with stent implantation. The stent was
      explanted electively 14 months after implantation and showed almost no
      endothelium formation. Therefore, there was no need for redo atrioseptectomy and
      the surgical intervention could be staged electively.

PMID- 15990954
TI  - Glutathione synthetase deficiency.
AB  - Glutathione (GSH), one of the most important antioxidants in the eukaryotic
      organism, is synthesized in a two-step procedure where the last step is catalysed
      by the enzyme glutathione synthetase (GSS). GSS deficiency is inherited autosomal
      recessively, and patients with this disease can be divided into three groups,
      according to their clinical phenotype. Mildly affected patients have mutations
      affecting the stability of the enzyme, causing a compensated haemolytic anaemia;
      moderately affected patients have, in addition, metabolic acidosis; and severely
      affected patients also develop neurological defects and show increased
      susceptibility to bacterial infections. Moderately and severely affected patients
      have mutations that compromise the catalytic properties of the enzyme. 5
      Oxoprolinuria appears in all three groups, but is more pronounced in the two
      latter groups. Today, no cure can be offered these patients; they are given
      vitamins C and E to boost their antioxidant levels, and bicarbonate to correct
      metabolic acidosis.

PMID- 15990955
TI  - Phosphorylation of p27(BBP)/eIF6 and its association with the cytoskeleton are
      developmentally regulated in Xenopus oogenesis.
AB  - p27BBP/eIF6 is an evolutionarily conserved regulator of ribosomal function. It is
      necessary for 60S biogenesis and impedes improper joining of 40S and 60S
      subunits, regulated by protein kinase C or Efl1p. No data on p27BBP/eIF6 during
      early development of Metazoa are available. We studied the distribution, post
      translational changes and association with the cytoskeleton of p27BBP/ eIF6
      during Xenopus oogenesis and early development. Results indicate that p27BBP/eIF6
      is present throughout oogenesis, partly associated with 60S subunits, partly free
      and with little cytoskeleton bound. During prophase I, p27BBP/eIF6 is detected as
      a single band of 27-kDa. Upon maturation induced by progesterone or protein
      kinase C, a serine-phosphorylated 29 kDa isoform appears and is kept throughout
      development to the neurula stage. Confocal microscopy showed that the
      distribution of p27BBP/eIF6 and its association with the cytoskeleton varies
      according to oogenesis stages. Briefly, in stage 6 oocytes, p27BBP/eIF6 has a
      limited dot-like distribution, and does not co-localize with cytokeratin, whereas
      upon maturation it spreads throughout the cytoplasm. After fertilization, a large
      fraction coalesces around cytomembranes and a cytochalasin B-sensitive co
      localization with cytokeratin occurs. RNAse removes p27BBP/eIF6 from the
      cytokeratin fibres. Developmental data suggest a role of p27BBP/eIF6 in
      controlling ribosomal availability or regulating cross-talk between ribosomes and
      the cytoskeleton.

PMID- 15990956
TI  - Dual role of endogenous nitric oxide in tumor necrosis factor shock: induced NO
      tempers oxidative stress.
AB  - Tumor necrosis factor (TNF) is involved in pathologies like septic shock,
      inflammatory bowel disease and rheumatoid arthritis. TNF and lipopolysaccharide
      can incite lethal shock, in which cardiovascular collapse is centrally
      orchestrated by the vasodilating free radical nitric oxide (NO). However, NO
      synthase (NOS) inhibition causes increased morbidity and/or mortality, suggesting
      a dual role for NO. To investigate the potential protective role of NO during TNF
      shock, we treated mice with TNF with or without NOS inhibition. Experiments in
      endothelial- NOS- and inducible NOS-deficient mice identified inducible NOS as
      the source of protective NO. Distinctive TNF-induced lipid peroxidation,
      especially in liver and kidney, was aggravated by NOS inhibition. In addition,
      various antioxidant treatments and a phospholipase A2 (PLA2) inhibitor prevented
      sensitization by NOS inhibition. Together, these in vivo results indicate that
      induced NO not only causes hemodynamic collapse, but is also essential for
      curbing TNF-induced oxidative stress, which appears to hinge on PLA2-dependent
      mechanisms.

PMID- 15990957
TI  - Aluminum-triggered structural modifications and aggregation of beta-amyloids.
AB  - We investigated the structural effects induced by Al3+ on different beta-amyloid
      (Abeta) fragments at pH 7.4 and T=25 degrees C, with particular attention given
      to the sequences 1-40 and 1-42. Al3+ caused peptide enrichment in beta sheet
      structure and formation of solvent-exposed hydrophobic clusters. These
      intermediates evolved to polymeric aggregates which organized in fibrillar forms
      in the case of the Al3+-Abeta(1-42) complex. Comparative studies showed that Zn2+
      and Cu2+ were much less efficient than Al3+ in stimulating the spontaneous
      aggregation/fibrillogenesis of Abetas. Studies with liposomes as membrane models
      showed dramatic changes in the structural properties of the lipid bilayer in the
      presence of Al3+-Abeta complexes, suggesting a major role of Al3+ in Abeta
      induced cell dysfunction. Al3+ effects were abolished by desferrioxamine mesylate
      (DFO) only in solution. We concluded that, in vivo, DFO may act as a protective
      agent by preventing or reverting Abeta aggregation in the extracellular spaces.

PMID- 15990958
TI  - Genome-wide association study to identify SNPs conferring risk of myocardial
      infarction and their functional analyses.
AB  - Myocardial infarction might result from the interactions of multiple genetic and
      environmental factors, none of which can cause disease solely by each of
      themselves. Although molecular biological studies revealed that a number of
      proteins are possibly involved in its pathogenesis, little, if any genetic
      findings have been reported so far. To reveal genetic backgrounds of myocardial
      infarction, we performed a large-scale, case-control association study using
      92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have
      identified functional SNPs within the lymphotoxin-alpha gene (LTA) located on
      chromosome 6p21 that conferred susceptibility to myocardial infarction.
      Furthermore, we could identify galectin-2 protein as a binding partner of LTA
      protein. The association study further revealed that a functional SNP in LGALS2
      encoding galectin-2, which led to altered secretion of LTA, also indicated a risk
      of myocardial infarction. A combined strategy of genetic and molecularcellular
      biological approaches may be useful in clarifying pathogenesis of common
      diseases.

PMID- 15990959
TI  - Spectrin and calpain: a 'target' and a 'sniper' in the pathology of neuronal
      cells.
AB  - It is well documented that activation of calpain, a calcium-sensitive cysteine
      protease, marks the pathology of naturally and experimentally occurring
      neurodegenerative conditions. Calpain-mediated proteolysis of major membrane
      skeletal protein, alphaII-spectrin, results in the appearance of two unique and
      highly stable breakdown products, which is an early event in neural cell
      pathology. This review focuses on spectrin degradation by calpain within neurons
      induced by diverse conditions, emphasizing a current picture of multi-pattern
      neuronal death and a recent success in the development of spectrin-based
      biomarkers. The issue is presented in the context of the major structural and
      functional properties of the two proteins.

PMID- 15990960
TI  - Structural and dynamical features contributing to thermostability in alpha
      amylases.
AB  - In recent years an increasing number of studies on thermophilic and
      hyperthermophilic proteins aiming to elucidate determinants of protein
      thermostability have yielded valuable insights about the relevant mechanisms. In
      particular, comparison of homologous enzymes with different thermostabilities
      (isolated from psychrophilic, mesophilic, thermophilic and hyperthermophilic
      organisms) offers a unique opportunity to determine the strategies of thermal
      adaptation. In this respect, the medium-sized amylolytic enzyme alpha-amylase is
      a well-established representative. Various studies on alpha-amylases with very
      different thermostabilities (melting temperature T(m) = 40-110 degrees C) report
      structural and dynamical features as well as thermodynamical properties which are
      supposed to play key roles in thermal adaptation. Here, results from selected
      homologous alpha-amylases are presented and discussed with respect to some new
      and recently proposed strategies to achieve thermostability.

PMID- 15990961
TI  - Summary of the ASCO-JSCO joint symposium.

PMID- 15990962
TI  - Postoperative adjuvant therapy for completely resected early-stage non-small cell
      lung cancer.
AB  - Consensus on adjuvant therapy for completely resected non-small cell lung cancer
      until 2002 was as follows. (1) There was no significant impact of postoperative
      adjuvant chemotherapy based on meta-analysis and previous clinical trials. (2)
      Confirmatory studies are necessary in large-scale prospective clinical trials.
      However, recent mega trials have introduced epoch-making changes for
      postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. The
      effectiveness of UFT in N0 patients was confirmed. Patients with completely
      resected stage I non-small cell lung cancer, especially T2N0 adenocarcinoma, will
      benefit from adjuvant chemotherapy with UFT. The results of the International
      Adjuvant Lung Trial (IALT) have confirmed the meta-analysis in 1995. Also, both
      the JBR10 and Cancer and Leukemia Group B (CALGB) 9633 studies have also
      confirmed positive IALT results of the benefit for postoperative platinum-based
      chemotherapy in completely resected non-small cell lung cancer. Adjuvant
      chemotherapy for pathological stage IB to II, completely resected non-small cell
      lung cancer is standard care based on clinical trials. UFT showed the strongest
      evidence for IB in Japan. Platinum doublet chemotherapy with third-generation
      anticancer agents is also recommended. Adjuvant chemotherapy should be offered as
      standard care to patients after completely resected early stage non-small cell
      lung cancer. However, there is no evidence of the feasibility and efficacy for
      adjuvant chemotherapy with the platinum-based regimen in Japan. Careful
      management should be necessary in such treatment.

PMID- 15990963
TI  - Clinical trials of surgical treatment of malignant diseases.
AB  - The Dutch Gastric Cancer Study Group Trial was the first clinical phase III trial
      to be carried out in the field of cancer surgery. In spite of the excellent
      quality of the trial, it was heavily criticized for the poor quality of the
      treatment itself. Actually, the hospital mortality after the new surgical
      treatment (D2 lymph node dissection for gastric cancer) was unacceptably high. In
      surgical trials, special attention should be paid to quality issues specific to
      surgery. The first and the most important issue is the quality of treatment
      given. Reproducibility, homogeneity, and verifiability are the greatest problems
      in surgical trials. There are also some patient factors. If the patient is old,
      or fragile, or obese, the results of the surgical treatment can easily be
      affected by these factors. The surgeon can also be a prognostic factor,
      especially in complicated procedures or those requiring experience and training.
      Experience, including postoperative care, and dexterity affect the results. If
      surgeons do not know how to manage complications, mortality becomes very high.
      Because blinding is impossible in surgical trials, the treatment may easily be
      affected by personal preference or prejudice. To minimize the influence of these
      hampering factors, the procedures should be defined in as detailed a way as
      possible. If pretrial training or a feasibility study (phase II) is needed, it
      should be carried out properly for the patients' sake. An excellent design and
      excellent statistical analysis cannot lead to meaningful results if the quality
      of treatment is poor. Nonsense in, nonsense out.

PMID- 15990964
TI  - Prognostic value of thymidine phosphorylase activity in liver tissue adjacent to
      hepatocellular carcinoma.
AB  - BACKGROUND: Measurement of thymidine phosphorylase (TP) activity in normal liver
      tissue adjacent to hepatocellular carcinoma (HCC) may predict multicentric
      recurrence a long time after an operation. The authors investigated this activity
      in 92 patients with HCC who had a single HCC equal to or less than 5 cm. METHODS:
      Fresh samples (tumors with adjacent normal tissues) were collected from 92
      patients with HCC who underwent curative hepatic resection. The levels of TP
      activity in nonfixed, fresh, and frozen HCC specimens with adjacent noncancerous
      liver tissue were biochemically measured by using an enzyme-linked immunosorbent
      assay method. RESULTS: Patients who had a high TP level in normal liver tissue
      had significantly earlier recurrence (median disease-free survival, 819 days; 95%
      confidence interval [95% CI], 478-1044 days) compared with patients who had a low
      TP level (median disease-free survival, 1376 days; lower limit of 95% CI, 921
      days; P = 0.0171). Multivariate analysis showed that patients who had a low TP
      level in adjacent liver tissue had a 0.387-fold higher risk of postoperative
      recurrence compared with patients who had a high TP level (P = 0.0067).
      CONCLUSION: TP activity in normal liver tissue adjacent to HCC is related to
      tumor occurrence and may predict postoperative tumor recurrence.

PMID- 15990965
TI  - Positron emission tomography with 18F-fluoro-2-deoxyglucose for the detection of
      recurrent ovarian cancer.
AB  - BACKGROUND: Recurrent ovarian cancer is refractory and resistant to treatment in
      most patients, and no effective treatment for it has been established. Starting a
      treatment when tumors still consist of micro foci may contribute to improvement
      of prognosis. Therefore, the early diagnosis of relapse is important. METHODS:
      Among patients with epithelial ovarian cancer in whom initial treatment achieved
      remission between April 1998 and December 2003, those patients in whom the cancer
      related antigen (CA)125 level was increased during the subsequent follow-up
      period, or those who showed abnormal computed tomography (CT)/magnetic resonance
      imaging (MRI) findings despite normal CA125 levels, were examined by 18F-fluoro-2
      deoxyglucose - positron emission tomography (FDG-PET). We compared the rates of
      accurate diagnosis of recurrence achieved using CT/MRI, CA125, and FDG-PET in
      patients with a definitive diagnosis of relapse. RESULTS: We investigated 29
      patients with epithelial ovarian cancer. The sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and accuracy of FDG-PET
      were 84.6% (22/26), 100% (3/3), 100% (22/22), 42.9% (3/7), and 86.2% (25/29),
      respectively. These values were higher than the corresponding values obtained
      using CT/MRI or CA125 levels. CONCLUSION: FDG-PET may be very useful for
      identifying sites of recurrent ovarian cancer, although this procedure had a low
      NPV because of the high rate of false-negative findings for micro or cystic
      lesions.

PMID- 15990966
TI  - Treatment of androgen-independent, hormone-refractory prostate cancer with
      docetaxel in Japanese patients.
AB  - BACKGROUND: Although patients with prostate cancer with metastatic lesions
      initially respond to androgen ablation therapy, most patients ultimately develop
      a hormone-refractory state. Effective treatment for men with hormone-refractory
      prostate cancer (HRPC) has not been established. We performed a clinical study of
      docetaxel in HRPC patients, and evaluated its efficacy. METHODS: Nine patients
      with HRPC were administered 55 mg/m2 docetaxel, every 3 weeks, simultaneously
      with hormonal therapy, with a luteinizing hormone-releasing hormone analog, and
      daily oral dexamethasone. Change in serum prostate-specific antigen (PSA) was
      determined as the primary endpoint. RESULTS: The mean age of the patients was 64
      years (range, 49 to 76 years). Median follow-up time was 8.5 months (range, 5.3
      to 16.7 months). In eight patients whose pretreatment serum PSA was elevated, six
      patients (75.0%) had a PSA decline of more than 50%, and four (50.0%) had a PSA
      decline of more than 75%. Median time to progression for all patients was 7.9
      months (range, 0.0 to 11.6 months; 95% confidence interval [CI], 0.0 to 26.3).
      The median overall survival was 8.5 months (range, 5.3 to 16.7 months; 95% CI,
      8.1 to 13.8). Four of six patients (66.7%) with pain before treatment obtained
      pain relief and were able to discontinue analgesic agents. This regimen was well
      tolerated. Grade 3 or 4 neutropenia or leukocytopenia without fever was seen in
      three patients (33.3%). Only one patient required administration of granulocyte
      colony stimulating factor because of neutropenia. No other grade 3 or 4 toxicity
      was observed. CONCLUSION: Docetaxel was an active agent in Japanese HRPC
      patients, and was well tolerated in this population. To establish its efficacy
      and safety in Japanese HRPC patients, a large-scale study in Japan is warranted.

PMID- 15990967
TI  - Incidence of postoperative ileus after paraaortic lymph node dissection in
      patients with malignant gynecologic tumors.
AB  - BACKGROUND: Paraaortic lymph node metastasis is an important prognostic factor in
      gynecologic malignancy. However, paraaortic lymph node dissection (PAND) is not
      done routinely in Japan because of the difficulty of the procedure and the high
      incidence of complications. We performed PAND in 217 patients in a 7-year period.
      In the present study, we focused on the occurrence of postoperative ileus in
      patients who underwent PAND. METHODS: Two hundred and seventeen patients with
      malignant gynecologic tumors were operated on at our hospital between January
      1995 and August 2001. All patients underwent PAND and pelvic lymph node
      dissection (114 patients had a radical hysterectomy; 103 patients had a simple
      hysterectomy). We evaluated postoperative ileus in three categories of severity.
      RESULTS: The average operation time and blood loss in the patients with radical
      and simple hysterectomies with PAND were 317 min and 1158 g, and 246 min and 820
      g, respectively. The incidence of postoperative ileus was 12.9% (28/217).
      Although there were no significant differences in the occurrence of ileus between
      patients with the radical and simple hysterectomies (10.5% vs 15.5%), the
      incidence of ileus in patients with radical hysterectomy with PAND was
      significantly higher than that in a control group of patients with radical
      hysterectomy without PAND (10.5% vs 3.4%). However, in the PAND patients the
      postoperative ileus was mostly mild or moderate (10 mild cases, 15 moderate
      cases, and 3 severe cases). Severe ileus occurred in three patients with radical
      hysterectomy with PAND. Although a repeat operation was necessary for two of
      these three patients with severe ileus, they recovered uneventfully. CONCLUSION:
      PAND for malignant gynecologic tumors is a feasible and safe operative procedure,
      with a low incidence of postoperative ileus.

PMID- 15990968
TI  - Symptomatic metastases to the pituitary infundibulum resulting from primary
      breast cancer.
AB  - Metastatic spread into the brain is not infrequently seen in association with
      epithelial neoplasms such as lung and breast cancer, among others. In the
      majority of cases such spread entails a poor prognosis. Metastasic spread to the
      pituitary gland, specifically to the area of the infundibulum is, however, a more
      rare presentation. Most reported cases of metastatic disease to the pituitary are
      confined to the posterior lobe, probably related to the richer blood supply as
      compared to the anterior counterpart. The detection of pituitary metastasis is
      further complicated by the lack of specific associated symptomatology or definite
      radiologic diagnostic findings. We here describe the different clinical
      presentations of two patients with symptomatic pituitary stalk metastasis
      resulting from primary breast cancer; we also provide a systematic review of the
      literature.

PMID- 15990969
TI  - Laryngeal squamous cell carcinoma with ectopic production of granulocyte colony
      stimulating factor and parathyroid hormone-related protein.
AB  - It is known that malignant tumors occasionally produce hormone-like substances.
      However, they rarely produce two or more kinds of hormonal factors
      simultaneously. We describe the clinical, biochemical, and immunohistochemical
      findings in a patient with squamous cell carcinoma of the larynx associated with
      leukocytosis and hypercalcemia, without bone metastasis. The serum granulocyte
      colony-stimulating factor (G-CSF) level was 222 pg/ml (normal, < 38 pg/ml), and
      decreased to 15 pg/ml after surgery. The serum parathyroid hormone-related
      protein (PTHrP) level was 5.6 pmol/l (normal, < 0.5 pmol/l), and this also
      decreased, to less than 0.5 pmol/l. G-CSF and PTHrP increased again with tumor
      recurrence. The production of G-CSF from the tumor was confirmed by
      immunohistochemical staining with monoclonal antibody against human recombinant G
      CSF. The tumor was revealed to produce both G-CSF and PTHrP. In this article, we
      describe this very rare case of primary squamous cell carcinoma of the head and
      neck with the simultaneous ectopic production of more than one hormone-like
      substance.

PMID- 15990970
TI  - Adenoid cystic carcinoma of the uterine cervix.
AB  - Adenoid cystic carcinoma of the uterine cervix is a rare and peculiar variant of
      adenocarcinoma. This tumor represents 3% of all primary cervical adenocarcinomas,
      and it is locally aggressive and capable of metastasis to other organs even in
      its early stage. We report a case of adenoid cystic carcinoma stage IIIb that was
      successfully treated with radiotherapy. The patient shows no evidence of
      recurrent tumor at 5 years after radiotherapy. Generally, radiotherapy and
      chemotherapy are chosen as the first treatment, because this cancer is seen most
      commonly in the elderly.

PMID- 15990971
TI  - Weekly cisplatin administration concurrent with radiation therapy for
      locoregionally advanced nasopharyngeal carcinoma.
AB  - Radiation therapy (RT) with concurrent and adjuvant chemotherapy has been a
      widely accepted treatment for patients with locoregionally advanced
      nasopharyngeal carcinoma (NPC). We administered 40 mg/m2 cisplatin (CDDP) weekly,
      concurrently with RT, to six consecutive patients with locoregionally advanced
      NPC to evaluate its toxicity and efficacy. The median number of courses of CDDP
      administration was 4.5 and the median radiation dose was 69.7 Gy. Grade 3
      leukopenia was observed in three patients. All but one patient experienced grade
      3 or 4 skin reactions, pharyngitis, or dysphagia. All but one patient achieved a
      complete response, and the remaining patient received radical neck dissection for
      persistent cervical lymphadenopathies, which contained no cancer cells. All six
      patients were disease-free at last contact, with a median follow up of 23.5
      months. This regimen is well tolerated in patients with locoregionally advanced
      NPC.

PMID- 15990972
TI  - Amelanotic malignant melanoma of the esophagus: report of a patient with
      recurrence successfully treated with chemoendocrine therapy.
AB  - We report a case of primary amelanotic malignant melanoma of the esophagus, an
      extremely rare disease. A 58-year-old man was diagnosed as having middle
      esophageal cancer with lymph node metastasis, which was classified as esophageal
      cancer, Stage III:T3N1M0, by International Union Against Cancer (UICC) criteria.
      Preoperative chemotherapy was performed, but the response assessment was no
      change (NC). The patient underwent a subtotal esophagectomy via right thoracotomy
      and laparotomy. Reconstruction was performed by pulling up the stomach via the
      retrosternal route; the site of anastomosis was the neck. Adjuvant chemotherapy
      consisted of five courses of dacarbazine (DITC), nimustine (ACNU), vincristine
      (VCR), and interferon-beta. Eleven months after the surgery, computed tomography
      (CT) demonstrated recurrence in the upper mediastinum. The patient received
      chemoendocrine therapy, consisting of the first planned course of DITC, ACNU, and
      cisplatin (CDDP), given intravenously; and tamoxifen (TAM), given orally.
      Subsequently with a modified regimen of this therapy he attained a complete
      response (CR). In general, the prognosis of esophageal malignant melanoma is very
      poor. Although our patient had a recurrence, he is alive 4 years and 5 months
      after the surgery and 3 years and 6 months after the recurrence. The
      chemoendocrine therapy probably contributed to this outcome.

PMID- 15990973
TI  - Bone metastasis of intracranial meningeal hemangiopericytoma.
AB  - The authors investigated the clinical and radiological features and the treatment
      strategy for bone metastasis from a rare tumor, intracranial meningeal
      hemangiopericytoma. The clinical presentations and characteristic imagings were
      retrospectively reviewed in 15 bony metastatic lesions of four patients with this
      tumor. All four cases were initially diagnosed as atypical meningioma, and all of
      the bone metastases developed more than 10 years after the initial intracranial
      surgery. The common symptom induced by the metastatic lesions was pain. On plain
      roentgen films and computed tomography (CT), the involved bones showed thinning
      and expansion. On bone scintigraphy, a "cold-in-hot" appearance was typically
      observed. The clinical and radiological findings were diagnosed as bone
      metastasis from intracranial meningeal hemangiopericytoma. The prognosis after
      bone metastasis was relatively short compared to the long duration before bone
      metastases, because of the coexistence of other, visceral, metastasis. Combined
      with effective radiation therapy, surgical intervention for bone metastasis of
      this tumor should be carefully considered.

PMID- 15990974
TI  - Granuloma and cryptococcosis.
AB  - This review describes the general histopathological features of cryptococcosis in
      immunocompetent individuals, as well as in patients with acquired
      immunodeficiency syndrome (AIDS). Details of the histological examination of
      cryptococcal lesions are described, with the consideration of morphological
      modifications induced by treatment with highly active antiretroviral therapy
      (HAART). The essential histological features of cryptococcosis in individuals
      with impaired T-cell functioning are yeast-cell proliferation with a histiocytic
      response, but only minor lymphocytic and neutrophilic components. Several
      histological patterns of pulmonary cryptococcal lesions are introduced in this
      article, some of which could be graded with respect to the degree and type of
      inflammatory reaction. One pattern was a mild lesion consisting of scattered
      small foci of intraalveolar cryptococcal proliferation with a histiocytic
      response. Another pattern involved massive cryptococcal infection, which may have
      been simply more extensive than that in the mild lesion. Capillary involvement of
      alveolar septa should be understood as an important common finding in patients
      with AIDS who had not been treated with HAART. In those patients, the absence of
      T cells and a decreasing function of antigen-presenting activity in histiocytes
      were confirmed by immunohistological examination. These findings suggest that the
      lungs of AIDS patients without HAART offer little resistance to bloodstream
      dissemination by cryptococci. The unique histological feature demonstrated in
      patients treated with HAART is characterized by the presence of CD4+ cells,
      greater response of histiocytes and multinucleated giant-cell formation, and lack
      of massive capillary involvement.

PMID- 15990975
TI  - Evaluation of the anti-Trichophyton activity of a prodigiosin analogue produced
      by gamma-proteobacterium, using stratum corneum epidermis of the Yucatan
      micropig.
AB  - Prodigiosins (PGs) are known to be a family of natural red pigments,
      characterized by a common pyrrolydipyrrolylmethane skeleton structure with a C-4
      methoxy group, and some of these pigments have been isolated from some
      microorganisms. Members of the PG family have been reported to show several
      biological activities, such as immunosuppressive and cytotoxic activities.
      Recently, we discovered a bacterial strain (MS-02-063), from our microbial
      library, that produces large amounts of a PG analogue (PG-L-1). In this study, we
      examined the anti-Trichophyton activity of PG-L-1 (produced by strain MS-02-063)
      against clinically isolated Trichophyton spp., by a method using stratum corneum
      epidermis (SCE) of the Yucatan micropig, which is suitable for estimating the
      antifungal activity of drugs in vitro. In the National Committee for Clinical
      Laboratory Standards (NCCLS) method, PG-L-1 showed potent antifungal activity
      against nine clinically isolated strains of Trichophyton spp., although the
      minimum inhibitory concentration (MIC) values were slightly higher than those of
      bifonazole. In spite of the lower efficiency of PG-L-1 transfer into SCE from
      medium than that of bifonazole, PG-L-1 transferred into SCE showed more potent
      antifungal activity than bifonazole, at lower concentrations.

PMID- 15990976
TI  - Effect of Helicobacter pylori on DNA synthesis of human epithelial cells.
AB  - The effect of Helicobacter pylori on DNA synthesis of human cultured cells was
      examined. Viable H. pylori strains were able to stimulate DNA synthesis by
      gastric cancer MKN45 cells (eight of eight strains) and laryngeal cancer HEp-2
      cells (seven of eight strains) but not by lung cancer A549 cells or fetal
      intestine Int407 cells. In contrast, neither heat-killed H. pylori nor culture
      supernatants of H. pylori other than SS-1 strain affected DNA synthesis of MKN45
      and HEp-2 cells. In contrast, water extracts of H. pylori strains inhibited DNA
      synthesis. Soluble outer membrane protein (OMP) of the SS-1 strain stimulated DNA
      synthesis of MKN45 cells but produced no alteration in cell cycle or apoptosis
      induction of MKN45 cells. To identify those proteins in the soluble OMP that were
      capable of stimulating DNA synthesis, the OMP was fractionated by fast
      performance liquid chromatography with a Mono Q column. The results suggest that
      two proteins with molecular weights of 18 and 45 kDa, respectively, are
      associated with stimulation of DNA synthesis by MKN45 cells.

PMID- 15990977
TI  - A murine model of pulmonary basidiomycosis by Schizophyllum commune.
AB  - Schizophyllum commune has recently emerged as a causative agent of human mycosis,
      but the details of its virulence are not yet known. To elucidate the
      pathogenicity of S. commune, a murine model of invasive pulmonary infection was
      established. ICR mice, not immunosuppressed or immunosuppressed by cortisone
      acetate, were infected with S. commune by intratracheal inoculation with agar
      beads containing the basidiospores. All immunosuppressed mice died within 2
      weeks. Pathology examination revealed massive mycelial invasion into the lungs,
      penetration into adjacent vessels, and systemic dissemination, suggesting much
      higher virulence of this fungus than was previously estimated. This is the first
      murine model of pulmonary infection by S. commune, which we believe can be of
      assistance during subsequent investigations of this infection.

PMID- 15990978
TI  - Surgical site infection surveillance after open gastrectomy and risk factors for
      surgical site infection.
AB  - Surgical site infection (SSI) surveillance was examined in gastric cancer
      patients who had undergone an open gastrectomy between 1997 and 2003 at Keio
      University Hospital in Tokyo, Japan. National Nosocomial Infections Surveillance
      (NNIS) reports and several studies have discussed SSI risk factors, but only open
      gastrectomy was analyzed by regression analysis. The purpose of this study was to
      examine these issues by performing a regression analysis for the prediction of
      SSI. SSI was defined by the surgical patient component according to the NNIS
      system (1999) produced by the Centers for Disease Control and Prevention.
      Patients undergoing an open gastrectomy were followed up and monitored for SSIs.
      Risk factors for SSI, after all factors were considered, were studied using
      single and multivariate analysis. The study enrolled 984 patients who had
      undergoing an open gastrectomy. Using multivariate and logistic regression
      analysis, the duration of the operation was identified as a [corrected] risk
      factor for SSI at open gastrectomy. Although numerous potential risk factors in
      surgical patients were examined, the duration of the operation was the only
      significant risk factor for SSIs after open gastrectomy.

PMID- 15990979
TI  - Bacterial food-borne illness outbreaks in northern Taiwan, 1995-2001.
AB  - How to reduce the occurrence of food-borne illness has always been one issue of
      great importance in Taiwan's disease prevention and control efforts, and it is
      important to determine, from survey results, whether the pathogens in Taiwan are
      the same or different from those in other countries. Accordingly, data on 1171
      food-borne illness outbreaks were collected from the Center for Disease Control
      (CDC) of the Department of Health in Taiwan. The patients and the cases were
      numbered according to the guidelines and definition of food poisoning given by
      the Department of Health in Taiwan. All rectal swabs for culture were collected
      from the CDC. During 1995 to 2001, 1171 outbreaks of food-borne illness,
      including 109,884 cases, were reported in northern Taiwan, of which 735 (62.8%)
      were caused by bacterial infection. Bacterial pathogens, particularly Vibrio
      parahaemolyticus (86.0%), Staphylococcus aureus (7.6%), and Salmonella spp.
      (4.9%) were the main etiologic agents. The responsible pathogens in Taiwan
      appeared to be quite different from those in Europe and the United States. It is
      important to establish a unique surveillance net of our own to prevent and
      control our situation of food-borne disease outbreaks effectively.

PMID- 15990980
TI  - Multicenter prospective study of procalcitonin as an indicator of sepsis.
AB  - The clinical significance of serum procalcitonin (PCT) for discriminating between
      bacterial infectious disease and nonbacterial infectious disease (such as
      systemic inflammatory response syndrome (SIRS)), was compared with the
      significance of endotoxin, beta-D: -glucan, interleukin (IL)-6, and C-reactive
      protein (CRP) in a multicenter prospective study. The concentrations of PCT in
      patients with systemic bacterial infection and those with localized bacterial
      infection were significantly higher than the concentrations in patients with
      nonbacterial infection or noninfectious diseases. In addition, PCT, endotoxin, IL
      6, and CRP concentrations were significantly higher in patients with bacterial
      infectious disease than in those with nonbacterial infectious disease (P<0.001,
      P<0.005, P<0.001, and P<0.001, respectively). The cutoff value of PCT for the
      discrimination of bacterial and nonbacterial infectious diseases was determined
      to be 0.5 ng/ml, which was associated with a sensitivity of 64.4% and specificity
      of 86.0%. Areas under the receiver operating characteristic curves (POCs) were
      0.84 for PCT, 0.60 for endotoxin, 0.77 for IL-6, and 0.78 for CRP in the combined
      group of patients with bacterial infectious disease and those with nonbacterial
      infectious disease, and the area under the ROC for PCT was significantly higher
      than that for endotoxin (P<0.001). In patients diagnosed with bacteremia based on
      clinical findings, the positive rate of diagnosis with PCT was 70.2%, while that
      of blood culture was 42.6%. PCT is thus essential for discriminating bacterial
      infection from SIRS, and is superior in this respect to conventional serum
      markers and blood culture.

PMID- 15990981
TI  - A case of necrotizing fasciitis caused by coagulase-negative staphylococcus:
      utility of magnetic resonance imaging for the preoperative diagnosis of
      necrotizing fasciitis.
AB  - A 70-year-old woman presented with fever and pain in the right lower extremity.
      Fat-suppressed gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI)
      showed contrast-enhanced fascia, fluid accumulation, and hypointense signals in
      the muscles. Surgical interventions including incisions and insertion of drainage
      tubes were performed on the basis of the MRI findings. The histopathological
      examinations of surgically obtained biopsy specimens demonstrated suppurative
      fasciitis, widespread myonecrosis, and thromboses of the vessels, all of which
      were compatible with a diagnosis of necrotizing fasciitis. The bacterial cultures
      were positive for a coagulase-negative staphylococcus. Following the surgical
      interventions, the patient was successfully treated by aggressive antimicrobial
      therapy. MRI can thus be useful for differentiating necrotizing fasciitis from
      nonnecrotizing soft tissue infection and for planning the treatment of
      necrotizing fasciitis.

PMID- 15990982
TI  - Efficacy of pazufloxacin mesilate in Legionnaires' disease: a case report and in
      vitro study of the isolate.
AB  - We report here a case of culture-proven Legionnaires' disease successfully
      treated with intravenous injection of pazufloxacin mesilate (PZFX), a
      fluoroquinolone newly approved in Japan. The patient was a 51-year-old man
      hospitalized after a diagnosis of community-acquired pneumonia. Legionella
      pneumophila SG1 was isolated from the patient's bronchoalveolar lavage (BAL)
      fluid, and the soluble antigen of the bacterium was detected in the fluid as
      well. Subsequently, intravenous PZFX was administered for a week and proved
      markedly effective. An in vitro study confirmed that PZFX had excellent
      extracellular and intracellular activity against the isolate from the patient.
      This case suggests that PZFX is an option for treating Legionnaires' disease.

PMID- 15990983
TI  - Nocardial epidural abscess of the thoracic spinal cord and review of the
      literature.
AB  - Nocardia is a potential cause of opportunistic infection in organ-transplant
      recipients. We report an epidural abscess causing acute paraparesis in a patient
      with a rejected renal transplant and chronic liver disease. Early drainage and
      treatment with imipenem and trimethoprim-sulfamethoxasole improved the patient's
      neurologic status.

PMID- 15990984
TI  - [Survival factors in the treatment of hereditary retinal degeneration].
AB  - Hereditary retinal degeneration is characterized by apoptotic photoreceptor loss,
      a process governed by intricate molecular interplay and initiated when
      proapoptotic signals predominate in the individual cell. Identification of
      molecules involved and their actions has paved the way for testing the ones with
      anti-apoptotic functions in models of inherited retinal degeneration. Many of
      these factors are able to slow the course of the degeneration. However, to date
      no such treatment has been able to stop or even prevent the devolution of the
      disorder. Moreover, preservation of morphology does not necessarily correlate
      with preservation of ERG function. Deepened understanding of the pro- and anti
      apoptotic networks is clearly needed for survival factors to be feasible for
      therapy in humans. In comparison, in a dog model of Leber's congenital amaurosis
      gene therapy could establish retinal function, thus supplying proof of efficacy
      of the method.

PMID- 15990985
TI  - [Adult Refsum disease. A retinal dystrophy with therapeutic options].
AB  - Adult Refsum disease is one of the few forms of tapetoretinal degenerations
      accessible for therapy. The disease is characterized by an elevated plasma
      phytanic acid level and high concentrations of phytanic acid in a variety
      tissues. Beside tapetoretinal degeneration, additional symptoms are chronic
      polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia,
      ichthyosis, skeletal malformations, and cardiac abnormalities. A diet low in
      phytanic acid leads to an amelioration of polyneuropathy and ataxia and slows or
      even stops the other manifestations. This beneficial effect of dietary
      precautions requires the need to get hold of as much patients as possible but
      better all of them. The ophthalmologist plays a crucial role to this end because
      of the early manifestation of the tapetoretinal degeneration. A delay of 11 years
      between the appearance of first symptoms and the diagnosis of Refsum disease, as
      reported in the literature, is not acceptable.

PMID- 15990986
TI  - Bowel colonization with resistant gram-negative bacilli after antimicrobial
      therapy of intra-abdominal infections: observations from two randomized
      comparative clinical trials of ertapenem therapy.
AB  - The selection of resistant gram-negative bacilli by broad-spectrum antibiotic use
      is a major issue in infection control. The aim of this comparative study was to
      assess the impact of different antimicrobial regimens commonly used to treat
      intra-abdominal infections on the susceptibility patterns of gram-negative bowel
      flora after completion of therapy. In two international randomized open-label
      trials with laboratory blinding, adults with complicated intra-abdominal
      infection requiring surgery received piperacillin-tazobactam (OASIS 1) or
      ceftriaxone/metronidazole (OASIS II) versus ertapenem for 4-14 days. Rectal swabs
      were obtained at baseline, end of therapy, and 2 weeks post-therapy. Escherichia
      coli and Klebsiella spp. were tested for production of extended-spectrum beta
      lactamase (ESBL). Enterobacteriaceae resistant to the agent used were recovered
      from 19 of 156 (12.2%) piperacillin-tazobactam recipients at the end of therapy
      compared to 1 (0.6%) patient at baseline (p<0.001) in OASIS I, and from 33 of 193
      (17.1%) ceftriaxone/metronidazole recipients at the end of therapy compared to 5
      (2.6%) patients at baseline (p<0.001) in OASIS II. Ertapenem-resistant
      Enterobacteriaceae were recovered from 1 of 155 and 1 of 196 ertapenem recipients
      at the end of therapy versus 0 and 1 ertapenem recipients at baseline in OASIS I
      and II, respectively. Resistant Enterobacteriaceae emerged significantly less
      often during treatment with ertapenem than with the comparator in both OASIS I
      (p<0.001) and OASIS II (p<0.001). The prevalence of ESBL-producers increased
      significantly during therapy in OASIS II among 193 ceftriaxone/metronidazole
      recipients (from 4 [2.1%] to 18 [9.3%]) (p<0.001), whereas no ertapenem recipient
      was colonized with an ESBL-producer at the end of therapy in either study.
      Selection for imipenem-resistant Pseudomonas aeruginosa was uncommon in all
      treatment groups. In these studies, the frequency of bowel colonization with
      resistant Enterobacteriaceae substantially increased in patients treated with
      either piperacillin-tazobactam or ceftriaxone/metronidazole, but not in patients
      treated with ertapenem.

PMID- 15990987
TI  - Reactivation of hepatitis B in an HIV-infected patient with antibodies against
      hepatitis B core antigen as the only serological marker.
AB  - Presented here is the first report of clinical reactivation of hepatitis B virus
      (HBV) in an HIV-infected patient who previously had anti-HBc as the only
      serological marker of past infection (anti-HBc alone). Reactivation occurred
      after lamivudine was removed from the patient's antiretroviral treatment regimen
      due to lack of virological response. HIV-infected patients frequently present
      anti-HBc alone, and in some cases this serological profile is associated with
      occult HBV infection. The current case demonstrates the importance of ruling out
      the possibility of occult infection in this patient group.

PMID- 15990988
TI  - [Detail study of angiotensin-receptor blockade versus ACE-inhibition in type 2
      diabetes with nephropathy].

PMID- 15990989
TI  - [Abdominal pain].
AB  - Abdominal pain can result from a variety of different intra- and extra-abdominal
      disorders. Given the wide variety of etiological triggers for this pain, the
      primary task during the first stage of the diagnostic work-up is to determine as
      soon as possible the underlying cause and the degree of emergency. The aim of
      this evaluation is to adapt the therapeutic measures which are necessary for a
      causal treatment to the individual situation. Contrary to somatic causes of
      abdominal pain, the availability of such a causal therapy for functional bowel
      disorders is still very limited. Given this dilemma, the therapeutic focus of
      abdominal pain associated with these functional syndromes has to be placed on
      symptom-oriented treatment.

PMID- 15990990
TI  - Synovial chondromatosis of the foot presenting with Lisfranc dislocation.
AB  - Primary synovial chondromatosis is rare in the foot. We report a case of synovial
      chondromatosis affecting multiple sites of the foot and causing bone erosions in
      a 44-year-old woman. Radiographs demonstrated erosions of multiple metatarsals
      including the tarsometatarsal joints, resulting in Lisfranc tarsometatarsal
      dislocation. Magnetic resonance imaging showed the widespread synovial
      proliferation and soft tissue masses affecting the foot and helped in arriving at
      a differential diagnosis and plan for needle biopsy. Diagnosis was made initially
      by needle biopsy under computed tomography guidance and was subsequently
      confirmed by histopathological assessment of the surgically excised synovial
      masses. To our knowledge, multifocal synovial chondromatosis causing Lisfranc
      dislocation in the foot has not been reported previously.

PMID- 15990992
TI  - The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on
      gliostatin/platelet-derived endothelial cell growth factor production in human
      fibroblast-like synoviocytes.
AB  - Gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) is known
      to have both angiogenic and arthritogenic activities. The purpose of this study
      was to investigate whether disease-modifying anti-rheumatic drugs (DMARDs) and
      steroids are involved in the regulation of GLS expression. Fibroblast-like
      synoviocytes (FLSs) obtained from patients with rheumatoid arthritis (RA) were
      cultured and stimulated by interleukin (IL)-1beta with or without DMARDs and
      steroids. The expression levels of GLS were determined using the reverse
      transcription-polymerase chain reaction and an ELISA. In cultured rheumatoid
      FLSs, the expression of GLS mRNA was significantly increased by stimulation with
      IL-1beta. By contrast, GLS mRNA levels in IL-1beta-stimulated FLSs were reduced
      by treatment with aurothioglucose (AuTG) and dexamethasone (DEX). These findings
      indicate that AuTG and DEX have anti-rheumatic activity, which is mediated via
      the suppression of GLS production. Neither methotrexate (MTX) nor sulfasalazine
      (SSZ) had a significant influence on GLS levels in our study.

PMID- 15990991
TI  - The potential value of blood biomarkers of intervertebral disk metabolism in the
      follow-up of patients with sciatica.
AB  - STUDY DESIGN: This is a prospective study with a follow-up period of 4 years.
      OBJECTIVES: The study aimed to evaluate the possible clinical utility of three
      biomarkers [i.e., keratan sulfate (KS), hyaluronan, and cartilage oligomeric
      matrix protein] measured in peripheral blood in severe acute sciatica at intake
      and follow-up. SUMMARY OF BACKGROUND: Our previous study and others have pointed
      out the interest of different laboratory tests in the acute phase of sciatica.
      Several blood biomarkers have been reported useful in the long-term follow-up of
      patients with osteoarthritis. We have found no information about the potential
      interest of these tests in spinal disorders. METHODS: Patients were admitted to
      the hospital for intensive conservative management of acute sciatica (n=82). A
      subgroup of patients (n=33) was selected based on the duration of symptoms at
      visit 1, and included those with the shortest (n=24) as well as those with the
      longest (n=9) duration of sciatica. Blood samples were drawn, centrifuged, and
      the plasma frozen. Antigenic KS, hyaluronan, and cartilage oligomeric matrix
      protein were measured by ELISA. Patients were re-evaluated at an average of 4.3
      years (range: 2.1-6.8 years). RESULTS: Thirty-three subjects with an average age
      of 49.2+/-10.2 years participated. At intake, levels of the three biomarkers
      evaluated were within the range of normal values. No significant differences were
      found between the results of patients with a short history of sciatica (< or =3
      weeks) and those with a long duration of symptoms (>20 weeks). At follow-up, a
      significant increase (P<0.05) in all three biomarkers was found. CONCLUSIONS: A
      single measurement of these three biomarker molecules does not seem to have any
      diagnostic or therapeutic relevance in patients with acute radicular compression.
      The significance of the increase in all three biomarkers after a mean follow-up
      of 4.3 years is unclear; it might reflect metabolic processes involved in
      degenerative spinal disorders. Even though we found no correlation with clinical
      outcome, we believe that more research is needed.

PMID- 15990993
TI  - The importance of alpha-fodrin antibodies in the diagnosis of Sjogren's syndrome.
AB  - OBJECTIVE: We wanted to determine the prevalence of IgA and IgG antibodies
      against alpha-fodrin in the patients with primary and secondary Sjogren's
      syndrome (SS) and also to compare with anti-Ro and anti-La antibodies in the
      diagnosis of SS. METHODS: We tested the prevalence of anti-alpha-fodrin IgA, IgG,
      anti-Ro, anti-La antibodies, anti-nuclear antibodies (ANA) and rheumatoid factor
      (RF) in naive patients with primary (n = 20) and secondary SS (n = 20)
      (Rheumatoid Arthritis [RA]+SS, n = 10; Systemic Lupus Erythematosus [SLE] + SS, n
      = 10), RA (n = 10), SLE (n = 10) and in healthy controls (n = 20). Salivary gland
      biopsies were performed in the patients with primary and secondary SS. RESULTS:
      In primary SS, anti-alpha-fodrin IgA, IgG, anti-Ro and anti-La antibodies were
      detected as 20, 10, 55 and 20% respectively. In RA + SS, anti-alpha-fodrin IgA
      was detected to be 10% and IgG was negative; however, anti-Ro antibodies and anti
      La antibodies were found to be 40% and 20% respectively. In SLE + SS, anti-alpha
      fodrin IgA was found to be 20% and IgG was found to be 10%, but anti-Ro and anti
      La antibodies were found to be 90% and 20% respectively. Alpha-fodrin antibodies
      were not detected in RA, SLE and healthy controls. CONCLUSION: The detection of
      anti-alpha-fodrin antibodies by used ELISA does not give much contribution to the
      diagnosis of SS, and anti-Ro and anti-La are still useful serological markers in
      the diagnosis of SS.

PMID- 15990994
TI  - Treatment for HTLV-I associated arthropathy: a case study and synovial tissue
      culture analysis.
AB  - OBJECTIVE: There are few reports regarding the treatment of HTLV-I associated
      arthropathy (HAAP). This is a case study describing the treatment of a patient
      diagnosed with HAAP. We also analyzed the effects of various agents on cultured
      synovial tissue explants from the patient. METHODS: Arthroscopic synovectomy of
      the left knee was performed. We investigated the effects of pirarubicin (THP),
      bestatin, betamethasone, and hyaluronic acid (HA) in synovial tissue culture to
      evaluate the efficacy of these medications. RESULTS: Swelling and pain of the
      left knee was transiently diminished after synovectomy. However, bilateral
      swelling of the knees and C reactive protein (CRP) concentrations were increased.
      In the explant culture experiments, CD8+ cells decreased with the addition of
      bestatin, betamethasone, and HA. The structure of synovial cells was preserved by
      the addition of HA. However, the addition of THP induced fibrosis of synovial
      tissues, increased cells without nuclei, and diminished fascin-expressing cells.
      CONCLUSION: THP inhibited, but HA preserved the structure of hypertrophic
      synovial cells. Scopic synovectomy effectively improved joint effusion and pain;
      however, the effect was transient, and additional treatment with predonisolone
      was required. Therefore, it is important to develop a more effective treatment
      for HAAP.

PMID- 15990995
TI  - Myeloperoxidase cytochemical negativity: an unexpected but intrinsic property of
      blasts of all phases of chronic myeloid leukemia.
AB  - Myeloperoxidase (MPO) cytochemical activity, recognized as a very important
      hallmark of myeloblasts, is generally negative in chronic myeloid leukemia (CML)
      blast crisis (BC). Because this finding is unexpected, being not in keeping with
      the myeloproliferative nature of CML, we tried to ascertain if MPO cytochemical
      negativity could be an intrinsic property of blasts of CML and hence present in
      the preblastic phases as well. Myeloperoxidase cytochemistry of peripheral blood
      blasts in 161 cases of CML, including 103 in chronic phase (CP) and 29 each in
      accelerated phase (AP) and BC, was assessed and compared with that of 30 cases of
      acute myeloid leukemia, AML-M2. Blasts of 97 (94.2%) of 103 cases of CP, 28
      (96.6%) of 29 cases of AP, and 22 (75.9%) of 29 cases of BC were negative for MPO
      (<3% MPO-positive blasts). Compared with the strong MPO positivity, both in terms
      of intensity and proportion, in the AML-M2 cases, the positivity in the CML cases
      was generally weak and was seen in a small number of blasts (5-15%), except in
      one case of BC with 20% positive blasts. Absence or, at times, weak MPO
      cytochemical activity is an intrinsic property of blasts of all phases of CML,
      and use of the term myeloblast in CML should be understood to refer to a cell
      with this property. This also explains why MPO cytochemistry, despite its high
      reputation as a myeloid-lineage marker, generally does not help in CML BC. CML BC
      should therefore be considered as a possible diagnosis along with acute
      lymphoblastic leukemia, AML-M0, AML-M7, etc., in the setting of MPO-negative
      blasts. Similarity between MPO expression pattern in CML, i.e., negative in
      blasts and positive in the more mature cells, and that during maturation of
      normal myeloid series of cells shows the deranged myelopoiesis of CML to be
      undisturbed at least with respect to MPO expression. There is need for a more
      comprehensive study of blasts of preblastic phases.

PMID- 15990996
TI  - [Recent insights into Rasmussen encephalitis].
AB  - Rasmussen encephalitis (RE) is a severe and at the same time pathophysiologically
      fascinating condition. The chronic inflammation affects one of the two cerebral
      hemispheres and destroys it during the disease process that lasts from months to
      years. The patients -- mostly children -- suffer from frequent pharmacoresistant
      seizures, often in the form of epilepsia partialis continua. In parallel to the
      atrophy of the affected hemisphere, the neurological functions associated with it
      decline continuously. This results in a final stage with a usually high-grade
      sensorimotor hemisyndrome, hemianopia, cognitive impairment and -- if the
      language-dominant hemisphere is affected -- aphasia. Research results in the last
      5 years have contributed to a deeper understanding of the pathogenesis of this
      condition. Formal diagnostic criteria have been proposed, and new therapeutic
      options have emerged by which the disease progression can be slowed or stopped.
      This article summarizes the current research results on the background of older
      data and gives recommendations regarding diagnostic and therapeutic procedures in
      RE patients.

PMID- 15990998
TI  - Naloxone does not attenuate the locomotor effects of ethanol in FAST, SLOW, or
      two heterogeneous stocks of mice.
AB  - RATIONALE: Previous studies suggest that some behavioral effects of ethanol and
      morphine are genetically correlated. For example, mice bred for sensitivity
      (FAST) or insensitivity (SLOW) to the locomotor stimulant effects of ethanol
      differ in their locomotor response to morphine. OBJECTIVE: To evaluate a possible
      common mechanism for these traits, we examined the effect of naloxone, an opioid
      receptor antagonist, on ethanol- and morphine-induced locomotion in FAST and SLOW
      mice, as well as on ethanol-induced locomotion in two heterogeneous stocks of
      mice. METHOD: In experiments 1 and 2, naloxone was given to FAST and SLOW mice 30
      min prior to 2 g/kg ethanol or 32 mg/kg morphine, and locomotor activity was
      measured for 15 min (ethanol) or 30 min (morphine). In experiments 3 and 4,
      naloxone was administered 30 min prior to 1.25 g/kg ethanol, and locomotor
      activity was assessed in FAST mice and in a heterogeneous line of mice
      [Withdrawal Seizure Control (WSC)]. Experiment 5 assessed the effect of naloxone
      on ethanol-induced stimulation in outbred National Institutes of Health (NIH)
      Swiss mice. RESULTS: There was no effect of naloxone on the locomotor response to
      ethanol in FAST, SLOW, WSC, or NIH Swiss mice. However, naloxone did
      significantly attenuate the locomotor effects of morphine in FAST and SLOW mice.
      CONCLUSIONS: These results suggest that a common opioidergic mechanism is not
      responsible for the correlated locomotor responses to ethanol and morphine in
      FAST and SLOW mice, and that activation of the endogenous opioid system is not
      critical for the induction of ethanol-induced alterations in activity.

PMID- 15991000
TI  - Increased salivary cortisol after waking in depression.
AB  - RATIONALE: Cortisol hypersecretion is regarded as important in the
      pathophysiology of major depression. However, recent studies in community-based
      samples have been inconclusive. OBJECTIVE: To determine whether acutely
      depressed, medication-free subjects show an exaggerated release of cortisol in
      saliva in relation to awakening. METHODS: We studied the pattern of waking
      salivary cortisol in 20 unmedicated acutely depressed subjects and 40 healthy
      controls. RESULTS: In both groups, salivary cortisol increased rapidly after
      waking, peaking at 30 min. Overall, patients with acute depression secreted
      approximately 25% more cortisol than controls, though 60 min after waking, their
      cortisol levels were similar. CONCLUSIONS: Depressed patients in the community
      appear to have increased early morning cortisol secretion, but the demonstration
      of this effect requires control for time of waking.

PMID- 15990999
TI  - Discriminative stimulus and reinforcing effects of p-fluoro-L-deprenyl in
      monkeys.
AB  - RATIONALE: para-Fluoro-L-deprenyl (Fludepryl), a halogenated derivative of L
      deprenyl, shares structural similarities with amphetamine and may have potential
      as a medication for psychostimulant abuse. OBJECTIVES: p-Fluoro-L-deprenyl was
      evaluated for psychomotor stimulant, discriminative stimulus, and reinforcing
      effects in squirrel monkeys. METHODS: One group of monkeys was trained under a
      ten-response fixed-ratio (FR10) schedule of stimulus termination to discriminate
      between methamphetamine (0.32 mg/kg, i.m.) and saline. Other monkeys were trained
      to self-administer i.v. cocaine under either a simple FR10 schedule or a second
      order fixed-interval 5-min schedule with FR10 components. RESULTS: Full
      generalization to the methamphetamine-training stimulus was produced by an i.m.
      dose of 10.0 mg/kg p-fluoro-L-deprenyl. L-Deprenyl and the metabolites of p
      fluoro-L-deprenyl, p-fluoro-L-amphetamine, and p-fluoro-L-methylamphetamine were
      more potent, producing full generalization at doses of 1.0-3.2 mg/kg. Under the
      FR10 schedule of drug injection, persistent self-administration behavior was
      maintained by i.v. cocaine injections but not by injections of vehicle or
      injection doses of p-fluoro-L-deprenyl up to 1.0 mg/kg. However, p-fluoro-L
      deprenyl did maintain moderate levels of i.v. self-administration responding
      under the second-order schedule of drug injection. Peak response rates maintained
      by 0.1-mg/kg injections of p-fluoro-L-deprenyl were significantly greater than
      those associated with saline substitution, yet significantly lower than those
      maintained by cocaine or D-amphetamine. CONCLUSIONS: p-Fluoro-L-deprenyl has
      methamphetamine-like discriminative-stimulus properties in squirrel monkeys that
      appear at higher doses than for its parent compound, L-deprenyl. It also appears
      to function as a relatively limited reinforcer of intravenous self-administration
      behavior in monkeys trained to self-administer i.v. cocaine.

PMID- 15991001
TI  - Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for
      dopaminergic-mediated mechanisms.
AB  - RATIONALE: Currently available therapy for depression treatment is often
      associated with several undesirable side effects, and it is effective only in a
      certain portion of the population. Therefore, the identification of alternative
      therapeutic tools for the treatment of depression is still needed. OBJECTIVE: The
      present study analyzed the possible antidepressant-like effects of the Brazilian
      medicinal plant, Trichilia catigua, in rodents. Attempts were also made to
      investigate some of the possible mechanisms implicated in its actions. METHODS:
      The antidepressant-like effects of T. catigua extract were assessed in two
      species of rodents (mice and rats) by means of in vivo (forced swimming test) and
      in vitro (monoamine reuptake and release in synaptosomal preparations)
      approaches. RESULTS: Acute oral treatment with the extract of T. catigua produced
      antidepressant-like effects in the forced swimming model in both mice and rats.
      Anti-immobility actions of T. catigua extract in mice were significantly reversed
      by haloperidol or by chlorpromazine, but not by pimozide, ketanserin,
      spiroxatrine or p-chlorophenylalanine. In vitro, T. catigua extract concentration
      dependently inhibited the uptake and increased the release of serotonin, and
      especially of dopamine, from rat brain synaptosomal preparations. CONCLUSIONS:
      The present study provides convincing evidence for a dopamine-mediated
      antidepressant-like effect of the active principle(s) present in the
      hydroalcoholic extract of T. catigua in mice and rats when in vivo and in vitro
      strategies were employed. Therefore, a standardized T. catigua extract or its
      purified constituents could be of potential interest for the treatment of
      depressive disorders.

PMID- 15991002
TI  - Nicotine antagonizes caffeine- but not pentylenetetrazole-induced anxiogenic
      effect in mice.
AB  - RATIONALE: Nicotine and caffeine are widely consumed licit psychoactive drugs
      worldwide. Epidemiological studies showed that they were generally used
      concurrently. Although some studies in experimental animals indicate clear
      pharmacological interactions between them, no studies have shown a specific
      interaction on anxiety responses. OBJECTIVES: The present study investigates the
      effects of nicotine on anxiety induced by caffeine and another anxiogenic drug,
      pentylenetetrazole, in mice. The elevated plus-maze (EPM) test was used to
      evaluate the effects of drugs on anxiety. METHODS: Adult male Swiss Webster mice
      (25-32 g) were given nicotine (0.05-0.25 mg/kg s.c.) or saline 10 min before
      caffeine (70 mg/kg i.p.) or pentylenetetrazole (15 and 30 mg/kg i.p.) injections.
      After 15 min, mice were evaluated for their open- and closed-arm time and entries
      on the EPM for a 10-min session. Locomotor activity was recorded for individual
      groups by using the same treatment protocol with the EPM test. RESULTS: Nicotine
      (0.05-0.25 mg/kg) itself did not produce any significant effect in the EPM test,
      whereas caffeine (70 mg/kg) and pentylenetetrazole (30 mg/kg) produced an
      anxiogenic effect, apparent with decreases in open-arm time and entry. Nicotine
      (0.25 mg/kg) pretreatment blocked the caffeine- but not pentylenetetrazole
      induced anxiety. Administration of each drug and their combinations did not
      produce any effect on locomotor activity. CONCLUSIONS: Our results suggest that
      the antagonistic effect of nicotine on caffeine-induced anxiety is specific to
      caffeine, instead of a non-specific anxiolytic effect. Thus, it may extend the
      current findings on the interaction between nicotine and caffeine.

PMID- 15991003
TI  - Effects of a nicotine conjugate vaccine on the acquisition and maintenance of
      nicotine self-administration in rats.
AB  - RATIONALE: Immunization of rats against nicotine using a nicotine conjugate
      vaccine reduces the distribution of nicotine to brain in rats and attenuates some
      of nicotine's physiological and behavioral effects. It is not known whether such
      a vaccine can attenuate nicotine's reinforcing effects. OBJECTIVE: The present
      experiment was conducted to determine whether a nicotine conjugate vaccine could
      interfere with the acquisition and maintenance of nicotine self-administration
      (NSA) in rats given 23 h day(-1) access to nicotine. METHODS: To examine
      acquisition of NSA, rats were vaccinated with nicotine or control immunogen prior
      to being given access to a 0.01 mg kg(-1) infusion(-1) nicotine under a fixed
      ratio(FR) 1 schedule for week 1, FR 2 for week 2, and FR 3 for week 3.
      Acquisition of cocaine self-administration (CSA) was similarly examined to
      determine the specificity of vaccination effects. To examine maintenance of NSA,
      rats were initially trained to self-administer nicotine under an FR 3 schedule,
      and then vaccinated with nicotine or control immunogen while NSA continued to be
      monitored. RESULTS: NSA was significantly lower in vaccinated rats compared to
      controls during the acquisition protocol, with a 38% decrease in the number of
      infusions during the last week of training. The percentage of rats meeting
      acquisition criteria in the vaccinated group was lower (36%) than that in the
      control group (70%), but this difference was not statistically significant.
      Vaccination did not affect acquisition of CSA, demonstrating its specificity for
      nicotine. Maintenance of NSA was significantly reduced in vaccinated rats as
      compared to controls after the final vaccine injection, with a mean reduction of
      57%. There was no evidence in either protocol that vaccinated rats attempted to
      compensate for altered nicotine distribution by increasing nicotine intake.
      CONCLUSION: These data suggest that vaccination against nicotine can reduce the
      reinforcing effects of nicotine in rats and may have therapeutic potential for
      the treatment of tobacco dependence.

PMID- 15991004
TI  - Simplifying psychotropic medication regimen into a single night dosage and
      reducing the dose for patients with chronic schizophrenia.
AB  - RATIONALE: Taking psychotropic medications is frequently problematic from both
      consumers' and caregivers' perspective. Occasionally missed doses may lead to
      pervasive non-adherence with relapse a likely outcome. OBJECTIVE: To evaluate the
      simple medication regimen, all psychotropics were given at night for patients
      with chronic schizophrenia, who had been taking them at least twice a day for
      more than 12 weeks before the entry. METHODS: Switching of agents took place in
      two ways: converting only antipsychotic medications followed by other
      psychotropics, and changing all psychotropics simultaneously. Any psychotropics
      of little clinical significance were then cautiously minimized. Final evaluation
      was made 12 weeks after the competed dose consolidation. Patients finally rated
      their subjective impression on this intervention. RESULTS: Twenty-five patients
      were recruited in each treatment arm (50 in total). After switching, 11 got
      better, 29 remained stable whereas seven got worse, according to the Global
      Improvement. Three were not assessable. Overall, there were no relevant changes
      in clinical ratings including adverse effects. However, the chlorpromazine
      equivalent dose of antipsychotics and the number of total psychotropics were
      significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2
      (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35
      subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they
      favored the night-time regimen mainly because it was less complicated. Sedation
      in the morning was identified as an important adverse event, which should be
      addressed by reducing the dose. CONCLUSIONS: The procedure may be of value to
      counteract a recent trend of psychotropic polypharmacy in schizophrenia.

PMID- 15991005
TI  - Characteristics of Epstein-Barr virus associated childhood non-Hodgkin's lymphoma
      in the Republic of Korea.
AB  - To analyze the clinicopathologic characteristics of childhood non-Hodgkin's
      lymphoma (NHL) associated with Epstein-Barr virus (EBV), EBER in situ
      hybridization was performed in 80 cases of NHLs. EBER-positive lymphomas account
      for 25% (20/80) and include NK/T-cell lymphoma (6/6), aggressive NK-cell leukemia
      (1/1), peripheral T cell lymphoma (5/11), diffuse large B-cell lymphoma (5/14),
      hydroa-like T-cell lymphoma (1/1), marginal zone B-cell lymphoma (1/2), and post
      transplantation lymphoproliferative disorder (1/1). Other types including 19
      cases of Burkitt's lymphoma were negative. For 9 EBER-positive cases,
      immunohistochemical staining for LMP-1, and EBNA-2 was performed to determine the
      EBV latency pattern. Two of nine EBER-positive cases expressed both LMP-1 and
      EBNA-2. Clinically, patients with EBV-positive B-cell lymphomas were cured with
      chemotherapy, whereas EBV-associated NK- and T cell lymphomas pursued fatal
      clinical course. In conclusion, EBVs infected in childhood NHLs are frequently
      associated not only with NK- and T- cell lymphomas but also large B-cell
      lymphomas.

PMID- 15991006
TI  - Concomitant deregulation of HIF1alpha and cell cycle proteins in VHL-mutated
      renal cell carcinomas.
AB  - Renal cell carcinomas (RCCs) of the clear cell type are associated with
      alteration of the von Hippel-Lindau (VHL) tumour suppressor gene as well as
      subsequent stabilization and over-expression of hypoxia inducible factor (HIF),
      which causes up-regulation of cyclin D1. On the basis of their ability to
      interact with cyclin D1 we investigated a number of cell cycle proteins to shed
      further light on the downstream effects of HIF dysregulation. Expression of
      HIF1alpha, cyclin D1, cyclin-dependent kinase 4 and cyclin-dependent kinase
      inhibitors p16, p21 and p27 was studied by immunohistochemistry. Since
      NFkappaB1/RelA have been shown to bind to the cyclin D1 promoter, mRNA expression
      of these transcription factors was further analysed by quantitative PCR. In RCCs
      harbouring VHL mutations/hypermethylation, over-expression of HIF1alpha was
      parallelled by up-regulation of cyclin D1 and CDK4 and down-regulation of p21 and
      p27. Moreover, p27 expression was inversely correlated with tumour cell
      differentiation. Comparison of non-tumorous autologous kidney tissues revealed a
      significant down-regulation of NFkappaB1 mRNA expression in patients harbouring
      RCC with VHL mutations/hypermethylation. Our data support the notion of a link
      between VHL deficiency/HIF dysfunction and disturbances of cell cycle control in
      the tumorigenesis of VHL-negative RCC.

PMID- 15991007
TI  - Tracing origin of serrated adenomas with BRAF and KRAS mutations.
AB  - Serrated neoplasm of the colorectum raised many as-yet unanswered issues. To
      characterize serrated neoplasia pathway, we investigated BRAF and KRAS mutations
      in 35 traditional serrated adenomas. BRAF exons 11 and 15, and KRAS exon 2 were
      amplified by polymerase chain reaction and directly sequenced. BRAF V599E
      mutation was found in 27 serrated adenomas (77.1%), and KRAS mutations were found
      in 3 (8.6%) of 35 traditional serrated adenomas. In 13 cases, mixed polyps
      composed of traditional serrated adenomas and hyperplastic (serrated) polyps were
      observed, and seven of them showed the same BRAF mutations in both components.
      Somatic mutations of BRAF and KRAS genes were mutually exclusive. These findings
      suggest that BRAF mutations are early and a critical event in the serrated
      adenomas, and most serrated adenomas in both sides of colon may progress from
      microvesicular hyperplastic polyps via BRAF mutations, and some left-sided
      serrated adenomas develop via KRAS mutations.

PMID- 15991009
TI  - Does the brain become heavier or lighter after trauma? The long story of brain
      water content and its direct or indirect measurement.

PMID- 15991008
TI  - A quantitative computed tomography assessment of brain weight, volume, and
      specific gravity in severe head trauma.
AB  - BACKGROUND: Computed tomography DICOM images analysis allows a quantitative
      measurement of organ weight, volume and specific gravity in humans. METHODS: The
      brain weight, volume and specific gravity of 15 traumatic brain-injury patients
      (3+/-2 days after trauma) were computed using a specially designed software
      (BrainView). Data were compared with those obtained from 15 healthy subjects
      paired for age and overall intracranial volume. RESULTS: Hemisphere weight were
      91 g higher in patients than in controls (1167+/-101 vs 1076+/-112 g; p<0.05).
      Specific gravity of hemispheres (1.0367+/-0.0017 vs 1.0335+/-0.0012 g/ml;
      p<0.001), brainstem (1.0302+/-0.0016 vs 1.0277+/-0.0015 g/ml; p<0.001) and
      cerebellum (1.0396+/-0.0020 vs 1.0375+/-0.0015 g/ml; p<0.05) was significantly
      higher in traumatic brain injury (TBI) patients than in controls (all p<0.0001
      without interaction). This increase in specific gravity was evenly distributed
      between the hemispheres, the brainstem and the cerebellum, and the grey and white
      matter. It was more pronounced in the rostral than in the caudal areas of the
      hemispheres. It was independent of the volume of brain contusion, of the
      mechanism of head injury, of natremia and of initial Glasgow coma score.
      CONCLUSION: Human TBI patients present a diffuse increase in specific gravity.
      This observation is in sharp opposition with the data derived from the
      experimental literature.

PMID- 15991010
TI  - Successful long-term program for controlling methicillin-resistant Staphylococcus
      aureus in intensive care units.
AB  - OBJECTIVE: To evaluate the effectiveness of screening strategy and contact
      precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA).
      DESIGN AND SETTING: Prospective observational cohort from 1 February 1995 to 31
      December 2001 in three intensive care units (45 beds) in a French teaching
      hospital. PATIENTS: 8,548 patients admitted to the three ICUs had nasal screening
      on ICU admission and weekly thereafter. Contact precautions were used in MRSA
      positive patients. The following variables were collected: age, gender, severity
      score, length of stay, workload, and colonization pressure (percentage of patient
      days with an MRSA to the number of patient-days in the unit). Alcohol-based
      handrub solution was introduced in July 2000. We compared the period before this
      (P1) with that thereafter (P2). RESULTS: Of the 8,548 admitted patients 554
      (6.5%) had MRSA at ICU admission, and 456 of the 7,515 (6.1%) exposed patients
      acquired MRSA. Acquisition incidence decreased from 7.0% in P1 to 2.8% in P2.
      Independent variables associated with MRSA acquisition were: age (adjusted odds
      ratio 1.013), severity score (1.047), length of ICU stay (1.015), colonization
      pressure (1.019), medical ICU (1.58), and P2 (0.49). CONCLUSIONS: MRSA control in
      these ICUs characterized by a high prevalence of MRSA at admission was achieved
      via multiple factors, including screening, contact precautions, and use of
      alcoholic handrub solution. Our results after adjustment of risk factors for MRSA
      acquisition and the steady improvement in MRSA over several years strengthen
      these findings. MRSA spreading can be successfully controlled in ICUs with high
      colonization pressure.

PMID- 15991011
TI  - Risk factors for conversion to laparotomy during laparoscopic management of an
      ectopic pregnancy.
AB  - OBJECTIVE: To identify risk factors for conversion to laparotomy during
      laparoscopic management of ectopic pregnancy. METHODS: A retrospective chart
      review of patients who underwent laparoscopy for treatment of ectopic pregnancy,
      during a 32-month period (6/1999-2/2002), at the University of Miami Jackson
      Memorial Hospital. We identified 229 patients; 201 had a successful laparoscopy
      (non-converted group) and 28 who were converted to laparotomy (converted group).
      Variables analyzed between the two groups were demographic data, patient-related
      risk factors available to the surgeon prior to the surgery (previous laparotomy,
      previous laparoscopy, history of PID, history of endometriosis, diameter of
      ectopic pregnancy as measured by ultrasound, amount of free fluid on ultrasound,
      BMI), and surgeons' experience. RESULTS: Out of the 229 laparoscopies, 28 were
      converted to laparotomy (12.2%). The rate of conversion was significantly higher
      for less experienced compared to experienced surgeon (OR = 6.1, 95% CI = 2.35
      15.88). Significantly more women had a BMI > 30 kg/m2 in the converted group
      compared to the non-converted group (42% vs. 14%; OR = 4.28, 95% CI = 1.7-10.75)
      and the converted group had significantly higher rate of large free fluid
      reported on ultrasound compared to the non-converted group (21.42% vs. 7.46%; OR
      = 3.38, 95% CI = 1.04-10.61). CONCLUSION: Less experienced surgeon, BMI > 30
      kg/m2, and large amount of free fluid on ultrasound increase the risk of
      conversion to laparotomy during laparoscopic management of ectopic pregnancy.

PMID- 15991012
TI  - Destructive operations in modern obstetrics.
AB  - This is a retrospective study carried out over a period of 7 years at a tertiary
      care hospital to evaluate the indications, types and complications of destructive
      operations. During this period, 51 destructive operations were performed on women
      with obstructed labor and intrauterine fetal death. The most common operation
      performed was craniotomy (68.62%) followed by decapitation (19.60%), evisceration
      (7.84%) and cleidotomy (3.92%). The most common indication was cephalopelvic
      disproportion (31.25%). Out of 53 babies delivered (one triplet delivery), two
      were grossly malformed and 49.05% babies had birth weight between 3.0 kg and 4.0
      kg and 9.43% were macrosomic. A total of 45.09% women had complications like
      atonic PPH, vaginal and perineal tears, puerperal sepsis and urinary tract
      infection. However, there was no maternal death. It is felt that for the women
      who belong to poor socio-economic status and have poor compliance and who present
      late in labor with features of obstruction, intrauterine sepsis and fetal death,
      destructive operation is still a good option.

PMID- 15991013
TI  - Effect of fetal gender on maternal serum human chorionic gonadotropin levels
      throughout pregnancy.
AB  - OBJECTIVES: Maternal serum human chorionic gonadotropin (MshCG) levels are higher
      in pregnant women with female fetuses than in pregnant women with male fetuses in
      the third trimester of pregnancy. Our aim was to examine the effect of fetal sex
      on MshCG levels throughout the pregnancy. MATERIALS AND METHODS: Twenty-nine
      uncomplicated pregnancies (14 had male fetus and 15 had female fetus) were
      included in the study. MshCG levels were measured four times between 8-12, 14-18,
      24-28 and 32-36 weeks of pregnancy. RESULTS: MshCG levels were significantly
      higher in both sexes between 8-12 weeks than the other three measurement periods.
      At 8-12 and 14-18 weeks measurements, there were no sex related differences in
      the MshCG levels. At 24-28 (P<0.004) and 32-36 (P<0.001) weeks MshCG levels were
      significantly higher in pregnancies bearing female fetuses than those bearing
      male fetuses. CONCLUSIONS: Fetal gender has a significant effect on MshCG levels
      in the third trimester of pregnancy. Accordingly, no correlation seems to exist
      in the first and second trimesters.

PMID- 15991014
TI  - Necrotizing fasciitis after abdominal hysterectomy: a report on five cases.
AB  - Necrotizing fasciitis, a severe soft tissue infection, was first described 80
      years ago. It occurs rarely in obstetric and gynecology practice. We reviewed
      medical records of 2,894 women who had underwent an abdominal hysterectomy at the
      Social Security Agency Aegean Obstetrics and Gynecology Teaching Hospital between
      2001 and 2005, and identified 5 (0.17%) cases of necrotizing fasciitis, which are
      described.

PMID- 15991015
TI  - GnRH-antagonists in reproductive medicine.
AB  - Suppression of sex steroid production based on desensitisation and down
      regulation of pituitary gonadotropin-releasing hormone (GnRH)-receptors by
      agonistic GnRH-analogues resulting in the blockage of gonadotropin release from
      the anterior pituitary gland is a well-established approach in a variety of
      clinical conditions. Antagonistic analogues of GnRH exert their effect by
      competing with endogenous GnRH for pituitary binding sites. Because of the lack
      of any intrinsic activity of these compounds, the characteristic initial 'flare
      up' effect of GnRH-agonist administration is absent. A more rapid suppression of
      gonadotropin release from the pituitary gland can be achieved, enabling shorter
      treatment regimes in ovarian hyperstimulation for assisted reproduction. As yet,
      GnRH-antagonists have attained market approval only for the indication of
      premature luteinizing hormone (LH) surge prevention in controlled ovarian
      hyperstimulation and palliative treatment of advanced prostatic cancer. However,
      GnRH-antagonists may be useful in a variety of other malignant and non-malignant
      indications where rapid sex steroid suppression is desired, such as uterine
      leiomyomas, endometriosis, gynaecological cancers or benign prostatic
      hyperplasia. In the context of infertility treatment, available data on the
      application of GnRH-antagonists in the treatment of endometriosis and uterine
      leiomyomas are reviewed.

PMID- 15991016
TI  - Quantification of pancreatic exocrine function with secretin-enhanced magnetic
      resonance cholangiopancreatography: normal values and short-term effects of
      pancreatic duct drainage procedures in chronic pancreatitis. Initial results.
AB  - The aim of this study was to quantify pancreatic exocrine function in normal
      subjects and in patients with chronic pancreatitis (CP) before and after
      pancreatic duct drainage procedures (PDDP) with dynamic secretin-enhanced
      magnetic resonance (MR) cholangiopancreatography (S-MRCP). Pancreatic exocrine
      secretions [quantified by pancreatic flow output (PFO) and total excreted volume
      (TEV)] were quantified twice in ten healthy volunteers and before and after
      treatment in 20 CP patients (18 classified as severe, one as moderate, and one as
      mild according to the Cambridge classification). PFO and TEV were derived from a
      linear regression between MR-calculated volumes and time. In all subjects,
      pancreatic exocrine fluid volume initially increased linearly with time during
      secretin stimulation. In controls, the mean PFO and TEV were 6.8 ml/min and 97
      ml; intra-individual deviations were 0.8 ml/min and 16 ml. In 10/20 patients with
      impaired exocrine secretions before treatment, a significant increase of PFO and
      TEV was observed after treatment (P<0.05); 3/20 patients presented post
      procedural acute pancreatitis and a reduced PFO. The S-MRCP quantification method
      used in the present study is reproducible and provides normal values for PFO and
      TEV in the range of those obtained from previous published intubation studies.
      The initial results in CP patients have demonstrated non-invasively a significant
      short-term improvement of PFO and TEV after PDDP.

PMID- 15991017
TI  - Lymphocyte functions in dairy cows in hot environment.
AB  - This study was carried out to ascertain the effects of intense high environmental
      temperatures (HET) on lymphocyte functions in periparturient dairy cows. The
      study was undertaken from the beginning of March through the end of July 2003 in
      a commercial dairy unit located approximately 40 km north of Rome. Thirty-four
      Holstein cows were utilised in the study. Twenty-two of these cows gave birth in
      spring (SP cows), from 28 March to 30 April. The remaining 12 cows gave birth in
      summer (SU cows), between 15 June and 2 July. The two groups of cows were
      balanced for parity and were fed the same rations. Blood samples were taken 4, 3,
      2 and 1 week before calving, and 1, 2 and 4 weeks after calving, in order to
      evaluate peripheral blood mononuclear cell (PBMC) function in vitro, and to
      determine plasma cortisol concentrations. After isolation, the PBMC were
      stimulated with mitogens and their response in terms of DNA synthesis and IgM
      secretion was measured. During spring, either the day (9-20 h) or the night (21-8
      h) temperature humidity index (THI) was below the upper critical THI (72)
      established for dairy cows. During summer, the mean daily THI values were 79.5+/
      2.9 during the day and 70.1+/-4.7 during the night. Furthermore, during summer,
      three heat waves (a period of at least 3 consecutive days during which there were
      less than 10 recovery hours) occurred. Recovery hours were intended hours with a
      THI below 72. The first heat wave lasted 5 days, the second 6 days, and the third
      15 days. Compared to the SP cows, over the entire periparturient period the
      extent of DNA synthesis and IgM secretion levels were lower (P ranging from <0.01
      to 0.0001) and higher (P<0.01) respectively, in the SU cows. Before calving, the
      SU cows also presented higher (P<0.01) concentrations of plasma cortisol compared
      to the SP cows. This study indicates that the effects of HET on the immune
      response depend on the specific immune function under consideration, and that
      neuroendocrinal changes due to HET may play a role in the perturbation of immune
      functions.

PMID- 15991018
TI  - A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and
      retention.
AB  - PURPOSE: [18F]3'-deoxy-3'-fluorothymidine (FLT) is a thymidine analog developed
      for imaging tumor proliferation with positron emission tomography (PET). To
      quantitatively assess images, the blood activities of FLT and its glucuronidated
      metabolite were measured and its kinetics analyzed. This study sought to limit
      the number of blood samples needed to measure FLT retention. METHODS: Total FLT
      activity was measured from 18 venous samples obtained over the first hour and
      dynamic imaging performed on 33 patients (average dose 350 MBq/mmol). The 5-, 10
      , 30- and 60-min samples were analyzed to measure the fraction of activity in FLT
      and its glucuronide. HPLC analysis was compared against a two-step column (Sep
      Pak) and metabolic rates measured using full and limited sampling. Probenecid (2
      g, oral) was given to two patients to determine whether imaging of the liver
      improved. RESULTS: At 60 min, 74% of the blood activity was unmetabolized (range
      57-85%). HPLC and Sep-Pak gave comparable results (r=0.97; average difference
      2.1%). For kinetic analysis, eight venous samples were sufficient to accurately
      measure total activity; for metabolite analysis, a single sample at 60 min
      yielded data with mean errors of 2.2%. The metabolic rate correlated with average
      SUV (r2=0.85; p=0.0002). An aorta input function gave kinetic results comparable
      to venous blood (r2=0.82). Probenecid did not improve imaging of the liver.
      CONCLUSION: Dynamic measurements of FLT retention can be used to calculate
      metabolic rates using a limited set of samples and correction for metabolites
      measured in a single sample obtained at 60 min.

PMID- 15991019
TI  - A novel complex of arginine-silicate improves micro- and macrovascular function
      and inhibits glomerular sclerosis in insulin-resistant JCR:LA-cp rats.
AB  - AIMS/HYPOTHESIS: The metabolic syndrome, with associated vasculopathy, is a major
      cause of cardiovascular disease and nephropathy. Impaired nitric oxide (NO)
      metabolism and endothelial function is an important component of the disease
      process. Increasing the availability of arginine, the precursor of NO, might
      enhance vascular function and protect against end-stage disease. MATERIALS AND
      METHODS: Insulin-resistant JCR:LA-cp rats were treated with arginine-silicate
      inositol complex or arginine-HCl at 1.0 g kg(-1) day(-1) (expressed as arginine
      HCl) from 8 to 13 weeks of age. The contractile/relaxant function of thoracic
      aortae and coronary arteries was assessed in vitro. Kidneys were assessed for
      severity of glomerular sclerosis. RESULTS: Arginine-silicate complex, but not
      arginine-HCl, normalised the hypercontractile response of the aorta to
      phenylephrine via an NO-dependent pathway. Coronary artery function, as indicated
      by reactive hyperaemia to warm ischaemia, was enhanced by both arginine
      compounds. In addition, the arginine-silicate complex increased coronary
      vasodilatation in response to bradykinin. Glomerular sclerosis was significantly
      reduced in rats treated with the arginine-silicate complex.
      CONCLUSIONS/INTERPRETATION: Treatment with exogenous arginine, in an efficiently
      absorbed form, improves vascular function and reduces nephropathy in an animal
      model of insulin resistance and cardiovascular disease, via mechanism(s)
      independent of insulin concentration. Enhancement of NO metabolism through
      increased availability of the precursor arginine appears to offer protection
      against micro- and macrovascular disease associated with the metabolic syndrome
      and insulin resistance.

PMID- 15991020
TI  - Global profiling of coxsackievirus- and cytokine-induced gene expression in human
      pancreatic islets.
AB  - AIMS/HYPOTHESIS: It is thought that enterovirus infections initiate or facilitate
      the pathogenetic processes leading to type 1 diabetes. Exposure of cultured human
      islets to cytolytic enterovirus strains kills beta cells after a protracted
      period, suggesting a role for secondary virus-induced factors such as cytokines.
      METHODS: To clarify the molecular mechanisms involved in virus-induced beta cell
      destruction, we analysed the global pattern of gene expression in human islets.
      After 48 h, RNA was extracted from three independent human islet preparations
      infected with coxsackievirus B5 or exposed to interleukin 1beta (50 U/ml) plus
      interferon gamma (1,000 U/ml), and gene expression profiles were analysed using
      Affymetrix HG-U133A gene chips, which enable simultaneous analysis of 22,000
      probe sets. RESULTS: As many as 13,077 genes were detected in control human
      islets, and 945 and 1293 single genes were found to be modified by exposure to
      viral infection and the indicated cytokines, respectively. Four hundred and
      eighty-four genes were similarly modified by the cytokines and viral infection.
      CONCLUSIONS/INTERPRETATION: The large number of modified genes observed
      emphasises the complex responses of human islet cells to agents potentially
      involved in insulitis. Notably, both cytokines and viral infection significantly
      (p<0.02) increased the expression of several chemokines, the cytokine IL-15 and
      the intercellular adhesion molecule ICAM-1, which might contribute to the homing
      and activation of mononuclear cells in the islets during infection and/or an
      early autoimmune response. The present results provide novel insights into the
      molecular mechanisms involved in viral- and cytokine-induced human beta cell
      dysfunction and death.

PMID- 15991021
TI  - Changes in adiponectin receptor expression in muscle and adipose tissue of type 2
      diabetic patients during rosiglitazone therapy.
AB  - AIMS/HYPOTHESIS: Adiponectin is important in the regulation of insulin
      sensitivity in man. Its receptors, adipoR1 and R2, have recently been identified,
      but their expression in adipose tissue and their regulation in response to
      insulin sensitisation of diabetic patients have never been assessed. We therefore
      explored the regulation of adipoR1/R2 and adiponectin expression in adipose
      tissue and skeletal muscle, and of adiponectin plasma concentrations in response
      to insulin sensitisation by rosiglitazone. METHODS: Patients with type 2 diabetes
      were studied in a double-blind, placebo-controlled crossover study, using in vivo
      arteriovenous techniques of measuring adipose tissue and muscle blood flow,
      combined with measurement of adipose tissue and skeletal muscle gene expression.
      RESULTS: Rosiglitazone treatment increased adiponectin concentrations by 69%.
      Skeletal muscle adipoR1 expression was down-regulated from 109.0 (70.1-165.7)
      (median [interquartile range]) to 82.8 (63.6-89.3) relative units (p=0.04), but
      adipose tissue adipoR1 expression was up-regulated from 5.3 (4.4-9.4) to 11.2
      (4.8-15.3) relative units (p=0.02) by rosiglitazone. In contrast to adipoR1
      expression, adipoR2 expression was not altered by rosiglitazone in either of the
      tissues. The increase in adipose tissue adipoR1 expression with rosiglitazone was
      associated with increased postprandial triglyceride clearance (r=0.67, p=0.05),
      and increased fasting fatty acid output (r=0.78, p=0.01) measured in subcutaneous
      adipose tissue. CONCLUSIONS/INTERPRETATION: AdipoR1 expression is up-regulated in
      adipose tissue but down-regulated in skeletal muscle by rosiglitazone. These data
      suggest that adipoR1 plays a role in mediating the effects of adiponectin in
      specific tissues in relation to insulin sensitisation.

PMID- 15991022
TI  - Pancreatic beta and alpha cells are both decreased in patients with fulminant
      type 1 diabetes: a morphometrical assessment.
AB  - AIMS/HYPOTHESIS: We have previously reported that fulminant type 1 diabetes is
      characterised by an absence of diabetes-related antibodies and a remarkably
      abrupt onset. However, little is known about the mechanism of beta cell
      destruction in this diabetes subtype, and to obtain insights into the aetiology
      of the disease, we investigated residual endocrine cells and the expression of
      Fas and Fas ligand in fulminant type 1 diabetes. METHODS: Residual beta and alpha
      cells were morphologically assessed in pancreatic tissue obtained by biopsy from
      five patients with recent-onset fulminant type 1 diabetes and five patients with
      recent-onset typical autoimmune type 1 diabetes. In addition, the expression of
      Fas and Fas ligand was evaluated by immunohistochemistry. RESULTS: In fulminant
      type 1 diabetes, beta and alpha cell areas were decreased significantly, compared
      with autoimmune type 1 diabetes and control subjects. In contrast, the alpha cell
      area was not decreased significantly in autoimmune type 1 diabetes, compared with
      that in control subjects. No Fas expression in islets and Fas ligand expression
      in CD3(+) cells in the exocrine pancreas were found in the fulminant type 1
      diabetic patients who underwent this evaluation. CONCLUSIONS/INTERPRETATION: Our
      study showed that beta and alpha cells are damaged in fulminant type 1 diabetes.
      In addition to the lack of Fas and Fas ligand expression, the results suggest
      that the mechanism of beta cell destruction in fulminant type 1 diabetes is
      different from that in autoimmune type 1 diabetes.

PMID- 15991023
TI  - -to: Wu AYT, Kong NCT, de Leon FA, Pan CY, Tai TY, Yeung VTF, Yoo SJ, Rouillon A,
      Weir MR, for the MAPS investigators (2005) An alarming high prevalence of
      diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria
      Prevalence (MAP) Study. Diabetologia 48: 17-26.

PMID- 15991024
TI  - Diabetes-associated HLA genotypes affect birthweight in the general population.
AB  - AIMS/HYPOTHESIS: The aim of our study was to test the hypothesis that HLA
      genotypes conferring risk of diabetes, cord blood autoantibodies, or both are
      associated with increased birthweight. METHODS: HLA genotypes were determined in
      dried blood spots of cord blood from a total of 16,709 children born to healthy
      mothers in the Diabetes Prediction in Skane (DiPiS) study, a population-based
      observational clinical investigation of newborn children. Children born to
      mothers with diabetes or gestational diabetes were excluded. Autoantibodies to
      glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were
      determined in standard radioligand binding assays. Birthweight was adjusted for
      gestational age and divided into quartiles. The upper quartile was defined as
      high relative birthweight (HrBW) and the lower quartile as low relative
      birthweight (LrBW). RESULTS: Genotypes conferring risk of type 1 diabetes were
      strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA
      DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR]
      [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is
      negatively associated with type 1 diabetes, was also associated with HrBW
      (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab
      were negatively associated with HrBW (OR [95% CI]=0.72 [0.56-0.93], p=0.01).
      Regression analysis showed that the HLA-associated increase in rBW was
      independent of confounding factors. CONCLUSIONS/INTERPRETATION: HLA genotypes may
      be associated with intrauterine growth independent of type 1 diabetes risk. The
      epidemiological observation that high birthweight is a risk factor for type 1
      diabetes could possibly result from a moderating effect on intrauterine growth of
      HLA genotypes conferring a high risk of diabetes.

PMID- 15991025
TI  - Identification of novel targets of cephaloridine in rabbit renal proximal tubules
      synthesizing glutamine from alanine.
AB  - Cephaloridine, which accumulates in the renal proximal tubule, is a model
      compound used for studying the toxicity of antibiotics towards this nephron
      segment. Several studies have demonstrated that cephaloridine alters renal
      intermediary and energy metabolism, but the mechanism by which this compound
      interferes with renal metabolic pathways remains incompletely understood. In an
      attempt to improve our knowledge in this field, we have studied the influence of
      cephaloridine on the synthesis of glutamine, which represents a key metabolic
      process involving several important enzymatic steps in the rabbit kidney. For
      this, suspensions of rabbit renal proximal tubules were incubated for 90 and 180
      min in the presence of 5 mM alanine, an important glutamine precursor, both in
      the absence and the presence of 10 mM cephaloridine. Glutamate accumulation and
      glutamine synthesis were found to be inhibited by cephaloridine after 90 and 180
      min of incubation, and cephaloridine accumulation in the renal proximal cells
      occurred in a time-dependent manner. The renal proximal tubule activities of
      alanine aminotransferase and glutamate dehydrogenase, which initiates alanine
      removal and releases the ammonia needed for glutamine synthesis, respectively,
      were inhibited to a significant degree and in a concentration-dependent manner by
      cephaloridine concentrations in the range found to accumulate in the renal
      proximal cells. Citrate synthase and glutamine synthetase activities were also
      inhibited by cephaloridine, but to a much lesser extent. The above enzymatic
      activities were not found to be inhibited when they were measured after
      successive dilutions of renal proximal tubules incubated for 180 min in the
      presence of 5 mM alanine and 10 mM cephaloridine. When microdissected segments
      (S1-S3) of rabbit renal proximal tubules were incubated for 180 min with 5 mM
      alanine with and without 5 and 10 mM cephaloridine, glutamate accumulation and
      glutamine synthesis were also inhibited in the three renal proximal segments
      studied; the latter cephaloridine-induced inhibitions observed were concentration
      dependent except for glutamine in the S3 segment. These results are consistent
      with the view that cephaloridine accumulates and is toxic along the entire rabbit
      renal proximal tubule. They also demonstrate that cephaloridine interferes in a
      concentration-dependent and reversible manner mainly with alanine
      aminotransferase and glutamate dehydrogenase, which are therefore newly
      identified targets of the toxic effects of cephaloridine in the rabbit renal
      proximal tubule.

PMID- 15991026
TI  - Molecular cloning and genetic analysis of a symbiosis-expressed gene cluster for
      lolitrem biosynthesis from a mutualistic endophyte of perennial ryegrass.
AB  - Lolitrems are potent tremorgenic mycotoxins that are synthesised by
      clavicipitaceous fungal endophytes of the Epichloe/Neotyphodium group in
      association with grasses. These indole-diterpenes confer major ecological
      benefits on the grass-endophyte symbiotum. A molecular signature for diterpene
      biosynthesis is the presence of two geranylgeranyl diphosphate (GGPP) synthases.
      Using degenerate primers for conserved domains of fungal GGPP synthases, we
      cloned two such genes, ltmG and ggsA, from Neotyphodium lolii. Adjacent to ltmG
      are two genes, ltmM and ltmK, that are predicted to encode an FAD-dependent
      monooxygenase and a cytochrome P450 monooxygenase, respectively. The cluster of
      ltm genes is flanked by AT-rich retrotransposon DNA that appears to have
      undergone extensive repeat induced point (RIP) mutation. Epichloe festucae, the
      sexual ancestor of N. lolii, contains an identical ltm gene cluster, but lacks
      the retrotransposon "platform'' on the right flank. Associations established
      between perennial ryegrass and an E. festucae mutant deleted for ltmM lack
      detectable levels of lolitrems. A wild-type copy of ltmM complemented this
      phenotype, as did paxM from Penicillium paxilli. Northern hybridization and RT
      PCR analysis showed that all three genes are weakly expressed in culture but
      strongly induced in planta. The relative endophyte biomass in these associations
      was estimated by real-time PCR to be between 0.3 and 1.9%. Taking this difference
      into account, the steady-state levels of the ltm transcripts are about 100-fold
      greater than the levels of the endogenous ryegrass beta-tubulin (beta -Tub1) and
      actin (Act1) RNAs. Based on these results we propose that ltmG, ltmM and ltmK are
      members of a set of genes required for lolitrem biosynthesis in E. festucae and
      N. lolii.

PMID- 15991027
TI  - Activation of group I metabotropic glutamate receptors depresses recurrent
      inhibition of motoneurons in the neonatal rat spinal cord in vitro.
AB  - This study examined whether activation of group I metabotropic glutamate
      receptors (mGluRs) could modulate synaptic inhibition of spinal motoneurons in
      the neonatal rat isolated spinal cord. Recurrent inhibitory postsynaptic
      potentials (IPSPs) generated by Renshaw cells were evoked via antidromic
      stimulation of motor axon collaterals and recorded intracellularly from lumbar
      motoneurons. The selective agonist of group I mGluRs DHPG (5 micromol L-1)
      depressed the recurrent IPSP, an effect prevented by the selective antagonist
      AIDA (500 micromol L-1). The depression by DHPG was use-independent and could be
      partly counteracted by increasing stimulus strength. Paired pulse depression
      observed at <or=50-ms intervals was blocked by DHPG in an AIDA-sensitive manner.
      These results suggest that, in the presence of DHPG, smaller recurrent IPSPs can
      contribute to the excitatory action of mGluR activation on spinal networks,
      including the generation of synchronous oscillations recorded from motoneurons.

PMID- 15991028
TI  - Otolith and canal integration on single vestibular neurons in cats.
AB  - In this review, based primarily on work from our laboratory, but related to
      previous studies, we summarize what is known about the convergence of vestibular
      afferent inputs onto single vestibular neurons activated by selective stimulation
      of individual vestibular nerve branches. Horizontal semicircular canal (HC),
      anterior semicircular canal (AC), posterior semicircular canal (PC), utricular
      (UT), and saccular (SAC) nerves were selectively stimulated in decerebrate cats.
      All recorded neurons were classified as either projection neurons, which
      consisted of vestibulospinal (VS), vestibulo-oculospinal (VOS), vestibulo-ocular
      (VO) neurons, or non-projection neurons, which we simply term "vestibular'' (V)
      neurons. The first three types could be successfully activated antidromically
      from oculomotor/trochlear nuclei and/or spinal cord, and the last type could not
      be activated antidromically from either site. A total of 1228 neurons were
      activated by stimulation of various nerve pair combinations. Convergent neurons
      were located in the caudoventral part of the lateral, the rostral part of the
      descending, and the medial vestibular nuclei. Otolith-activated vestibular
      neurons in the superior vestibular nucleus were extremely rare. A high percentage
      of neurons received excitatory inputs from two nerve pairs, a small percentage
      received reciprocal convergent inputs and even fewer received inhibitory inputs
      from both nerves. More than 30% of vestibular neurons received convergent inputs
      from vertical semicircular canal/otolith nerve pairs. In contrast, only half as
      many received convergent inputs from HC/otolith-nerve pairs, implying that
      convergent input from vertical semicircular canal and otolith-nerve pairs may
      play a more important role than that played by inputs from horizontal
      semicircular canal and otolith-nerve pairs. Convergent VS neurons projected
      through the ipsilateral lateral vestibulospinal tract (i-LVST) and the medial
      vestibulospinal tract (MVST). Almost all the VOS neurons projected through the
      MVST. Convergent neurons projecting to the oculomotor/trochlear nuclei were much
      fewer in number than those projecting to the spinal cord. Some of the convergent
      neurons that receive both canal and otolith input may contribute to the short
      latency pathway of the vestibulocollic reflex. The functional significance of
      these convergences is discussed.

PMID- 15991029
TI  - Activation of STAT3 signaling in axotomized neurons and reactive astrocytes after
      fimbria-fornix transection.
AB  - It is an open question to what extent neuroprotective mechanisms involving
      neurotrophic proteins are activated after central nervous system (CNS) lesions.
      Results from previous studies have indicated that ciliary neurotrophic factor
      (CNTF) and other members of the family of gp130-associated cytokines have
      neuroprotective effects on septohippocampal projection neurons axotomized by
      fimbria-fornix transection (FFT). Here we demonstrate that the transcription
      factor STAT3, a component of the primary cytokine signal transduction pathway, is
      transiently activated after FFT in the medial septum and in the lateral septum
      deafferented by the lesion. Immunocytochemical double-labeling showed nuclear
      signals for phosphorylated STAT3 in both types (GABAergic and cholinergic) of
      axotomized medial septal neurons around day 4 postlesion. This response
      temporally coincided with the cell-type-specific upregulation of the cytokine
      receptor components CNTF receptor alpha and LIF receptor beta in the same
      neurons. However, neuronal STAT3-activation was not abolished in CNTF- or LIF
      deficient mouse mutants. Furthermore, lesion-induced STAT3 signaling was also
      found in reactive GFAP-positive astrocytes of the medial and lateral septum.
      Interestingly, basal GFAP expression was reduced but postlesional upregulation
      was markedly enhanced in CNTF(-/-) animals. These results demonstrate transient
      activation of cytokine signaling after CNS lesion and suggest that gp130
      associated cytokines have multiple functions in the lesioned CNS by directly
      acting on axotomized neurons and on reactive astrocytes.

PMID- 15991030
TI  - Enhanced sensitivity to echo cues in blind subjects.
AB  - Many studies have reported that blind people compensate for their visual deficit
      by sharpening auditory processes. Here we compare the sensitivity to echo cues
      between blind and sighted subjects. In the first experiment, the blind subjects
      were more accurate than the sighted subjects in localizing an object on the basis
      of echo cues. To ensure that enhanced echolocalization abilities were not only
      due to the fact that blind individuals are more used to consciously paying
      attention to echo cues and are more familiar with this kind of tasks than sighted
      subjects, we tested both groups of subjects in a simple azimuthal localization
      task of auditory stimuli. In this second experiment, we evaluated the influence
      of irrelevant echo signals on auditory localization by placing the subjects and
      the sound sources at different positions in a sound reverberant room. Results
      revealed that blind subjects exhibit a higher sensitivity to echo signals than
      sighted subjects.

PMID- 15991032
TI  - Differences in visuomotor control between the upper and lower visual fields.
AB  - Danckert and Goodale [Exp Brain Res 137:303-308 (2001)] have shown that increases
      in movement time as target size decreased were greater when movements were
      performed in the lower compared with upper visual field. On this basis, they
      suggested that visual feedback processing was more effective in the lower visual
      field. However, despite the greater influence of target size on movement time for
      the lower compared to upper visual field, there were no differences in accuracy
      between visual fields for movements to the smallest targets. In the present
      study, we investigated whether superior performance would be observed in the
      lower visual field when movement times were constrained. Analysis of the
      variability in distance travelled at key kinematic markers (e.g. peak
      acceleration, peak velocity, and peak negative acceleration) revealed that limb
      trajectories were more consistent in the lower compared to upper visual field at
      the late stages of the movement. Also, squared correlation coefficients between
      the distance travelled at peak velocity and the distance at the end of the
      movement were smaller for movements performed in the lower visual field. These
      results imply that superior performance in the lower visual field was due to
      better utilization of visual feedback during movement execution.

PMID- 15991031
TI  - Modification of motor cortical excitability by an acetylcholinesterase inhibitor.
AB  - Acetylcholine powerfully modulates the excitability of neocortical neurones and
      networks. This study applied focal transcranial magnetic stimulation (TMS) to
      eight healthy subjects to test the effects of a single oral dose of 40 mg
      tacrine, an acetylcholinesterase inhibitor, on motor cortical excitability. It
      was found that tacrine decreased short-interval intracortical inhibition, and
      increased intracortical facilitation and short-interval intracortical
      facilitation. Motor thresholds, motor evoked potential amplitude, cortical silent
      period (CSP) duration, and measures of spinal and neuromuscular excitability
      remained unchanged. The effects peaked at 2-6 h and fully reversed after 24 h.
      All effects can be explained by a reduction of motor cortical GABAergic
      inhibitory neurotransmission via activation of presynaptic muscarinic M2
      receptors, but other more complex mechanisms may also have contributed and are
      discussed. The findings predict that acetylcholine has the potential to promote
      plasticity and learning in human motor cortex.

PMID- 15991033
TI  - Developmental fractionation and differential discrimination of the anti-saccadic
      direction error.
AB  - This partial re-analysis of the data of a total of 433 experimental sessions
      transfers the distinction of "express" and "regular" latency ranges from the pro
      saccade task to the latencies of the anti-saccadic direction errors. Express
      errors and express saccades (ES) loaded on one and the same PCA factor, and both
      variables were subject to only minor developmental changes from childhood to
      young adulthood. Regular direction errors loaded, with opposite signs, on the
      same factor as pro-saccadic reaction times and were unrelated to express errors;
      these direction errors showed substantial developmental changes. Our data
      contribute with new evidence from the anti-saccade task to the long standing
      debate on whether ES should be considered as a separate type of saccade. Anti
      saccadic direction errors with express latencies can be distinguished from those
      with regular latencies. Future anti-saccade task research should therefore
      analyse these error types separately in order to look for further evidence in
      favour of their conceptual and statistical distinction.

PMID- 15991034
TI  - Identification of intrinsic and reflex ankle stiffness components in stroke
      patients.
AB  - Reflex and intrinsic contributions to ankle stiffness were examined in 11 stroke
      patients with clinical evidence of ankle spasticity and nine gender-matched and
      age-matched controls. Subjects lay supine with one foot placed in a custom-fitted
      boot attached to an electro-hydraulic actuator. They were instructed to relax
      while pseudo-random binary sequence perturbations were applied to their ankle
      joint. The ankle position and torque, as well as EMG from the ankle dorsiflexors
      and plantarflexors were recorded. These were used to identify reflex and
      intrinsic components of ankle stiffness, using a non-linear, parallel-cascade,
      system identification method. Results demonstrated that the majority of stroke
      patients (7/11) had ankle stiffness similar to that of control subjects. In
      contrast, a minority of stroke patients (4/11) had an abnormal increase in ankle
      stiffness, most of which could be attributed to an increased reflex gain. Reflex
      stiffness increased as the ankle was dorsiflexed in all subjects. These results
      differ from a previous study showing that reflex gain and intrinsic stiffness
      were increased in all patients with spinal cord injury. This difference may
      reflect the different topography of the lesions in the two neurological
      conditions.

PMID- 15991035
TI  - Variability of motoneuron activation and the modulation of force production in a
      postural reflex of the hermit crab abdomen.
AB  - The tri-phasic reflex in hermit crab (Pagurus pollicarus) abdomen is triggered by
      local mechanoreceptors and is essential for postural control. The reflex consists
      of three stereotypical phases: a brief, high-frequency burst, a transient
      cessation of firing, and a late-discharge that is much lower in frequency than
      the initial burst. To better understand the reflex generation of force,
      variability of motoneuron discharge in each of five parameters of reflex
      activation was assessed. An intracellular current injection routine was used to
      correlate each of these parameters with force production. Phase 3 motoneuron
      firing frequency showed the greatest correlation with force production. Phase 3
      spike rate increased as a function of phase 2 duration, but the relationship
      between phase 2 duration and force produced by the reflex was weak. Junction
      potential amplitude decreased as phase 2 duration increased, and we hypothesize
      that this trend counteracts the increased phase 3 frequency, explaining the weak
      relationship of phase 2 duration and force production. Surprisingly, when phase 3
      frequency was held constant and phase 2 was increased in duration, the concurrent
      decrease in junction potential amplitude did not reduce force production.

PMID- 15991036
TI  - [Metatarsal osteotomies for hallux valgus].
AB  - In the surgical treatment of hallux valgus, proximal, diaphyseal, and distal
      osteotomies of the first metatarsal bone are commonly used. In an overview
      article different procedures are described as well as our own stage-adapted
      concept. Deformities with congruent articulation of the metatarsophalangeal joint
      are successfully treated with a distal chevron osteotomy. In an incongruent joint
      a distal soft tissue procedure is required for reduction of the joint. The
      metatarsus varus displacement is corrected with a proximal osteotomy of the first
      metatarsal bone. The indications and details of the surgical techniques are
      described as well as postoperative treatment, results, and possible
      complications.

PMID- 15991037
TI  - [Inserts for foot deformities].
AB  - Inserts are orthopedic aids in the treatment of foot disorders that result from
      changes of the static or dynamic situation. Provision of appropriate orthopedic
      devices can relieve the pain caused by forefoot deformities either in lieu of
      surgical intervention or in rare cases also following surgical treatment to
      improve the symptoms of residual pain.Available materials provide support,
      padding, and cushioning. Inserts are custom-made to measure and/or based on a
      plaster impression. Determining the indication, prescribing the inlay, and
      checking the orthosis are the tasks of the physician. One treatment option for
      relieving the pain of forefoot deformities consists in conservative therapy with
      an insert combining features of padding and support as well as adjusting a ready
      made shoe. The shoe and inlay should constitute a functional unit since often the
      optimal effect is only achieved with a combination of insert and orthopedic
      adjustment of the ready-made shoe.

PMID- 15991038
TI  - Cyanamide-induced aplastic anemia.
AB  - OBJECTIVE: To report a case of aplastic anemia in a patient treated with
      cyanamide, an alcohol-aversive drug. A 67-year-old man was admitted to hospital
      because of fever and pancytopenia. He had taken cyanamide for 6 months as an
      alcohol deterrent. No other risk factors for aplastic anemia were identified by
      interviewing the patient using a structured validated questionnaire. The results
      of bone-marrow biopsy showed severe aplastic anemia. Cyanamide was discontinued
      and the patient was treated according to a prespecified treatment protocol. One
      year after hospital admission, the patient was completely recovered with no need
      of immunosuppressive therapy. An objective causality assessment revealed that an
      adverse drug reaction was probable. DISCUSSION: As the efficacy of cyanamide has
      been questioned, due to the failure of various trials to show any benefit over
      placebo, its overall benefit/risk ratio should be reconsidered. The complete and
      rapid hematological recovery after discontinuation of the drug, and the absence
      of other factors that could explain the condition support the association of the
      present case of aplastic anemia with cyanamide. The mechanism remains unknown.
      Aplastic anemia is a rare but potentially serious adverse drug effect of
      cyanamide treatment. CONCLUSIONS: Given the poor evidence on the efficacy of
      cyanamide and the associated risk of aplastic anemia, its use in reducing alcohol
      consumption should be reconsidered.

PMID- 15991039
TI  - Communication of findings in pharmacovigilance: use of the term "signal" and the
      need for precision in its use.

PMID- 15991040
TI  - Adverse drug reactions related to drugs used in orthostatic hypotension: a
      prospective and systematic pharmacovigilance study in France.
AB  - OBJECTIVE: The aim of the present study was to investigate and characterise
      adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension
      (OH). METHODS: In this prospective and systematic study, 121 consecutive out
      patients suffering from primary (Parkinson's disease, pure autonomic failure,
      multiple system atrophy, Lewy bodies disease) or secondary (diabetic and non
      diabetic peripheral neuropathies) autonomic failure with symptomatic OH requiring
      pharmacological treatment with at least one drug marketed in France for OH were
      included together with six patients with refractory neurocardiogenic syncope.
      RESULTS: Of the patients, 85 received a monotherapy-mainly with midodrine (49.4%)
      and 42 received various combinations, the association of midodrine and
      fludrocortisone being the most frequent (66.6%). Of all the 127 patients, 88
      suffered from a total of 141 ADRs (1.60 per patient) with no statistical
      difference in ADR frequency between monotherapy and drug combinations (P>0.05).
      Among ADRs, 24 (17.0%) were considered as "serious" and 16 (11.3%) were
      considered as "unexpected", most of them observed with heptaminol. CONCLUSIONS:
      This study shows a high frequency of ADRs (especially serious and unexpected
      ADRs) with antihypotensive drugs. It strongly suggests the need for a better
      evaluation of the safety profile of antihypotensive drugs and improvement in
      summary of product characteristics.

PMID- 15991041
TI  - Population pharmacokinetics of tacrolimus in full liver transplant patients:
      modelling of the post-operative clearance.
AB  - OBJECTIVE: To investigate the population pharmacokinetics of tacrolimus in an
      adult liver transplant cohort using routine drug monitoring data and to identify
      patient characteristics that influence pharmacokinetic parameters. METHODS:
      Tacrolimus pharmacokinetics was studied in 37 adult patients using a population
      approach performed with NONMEM. RESULTS: A one-compartment open model with linear
      absorption and elimination adequately described the data. The apparent clearance
      (CL) was approximately zero in the immediate post-operative days (PODs) and then
      rapidly increased as a function of POD to reach a plateau. This was modelled as a
      sigmoid relationship with the characteristic parameters CL(max) (plateau),
      TCL(50) (time to obtain 50% of the plateau) and gamma (coefficient of
      sigmoidicity). This clearance model was thought to describe the hepatic function
      regeneration after transplantation. Typical population estimates (percentage
      inter-individual variability) of CL(max), TCL50, and gamma and apparent
      distribution volumes (V) were 36 l/h (43%), 6.3 days (33%), and 4.9 l and 1870 l
      (49%), respectively. The CL(max) was negatively related to plasma albumin, and
      TCL50 was positively related to aspartate amino transferase (ASAT). Bayesian
      estimations performed at different POD times indicated that acceptable precisions
      in individual pharmacokinetic predictions could be obtained after the 15th POD.
      CONCLUSION: Tacrolimus clearance modelling showed that there was a large
      variation in individual CL estimates up to the 15th day post-surgery. After this
      period, the mean error resulting from the Bayesian estimation was strongly
      decreased and this estimation method could be applicable and should limit
      tacrolimus monitoring.

PMID- 15991042
TI  - The effects of saturated fatty acids on Giardia duodenalis trophozoites in vitro.
AB  - Giardia duodenalis is a protozoal, intestinal parasite that is a common
      aetiological agent of infectious diarrhoea in humans worldwide. Chemotherapeutic
      intervention presently offers a limited range of drugs and these are usually only
      employed after clinical diagnosis. Moreover, these drugs are ineffective against
      the infectious cysts, can produce unpleasant side effects, and are expensive with
      limited availability in developing countries. Frequent reports of drug toxicity,
      treatment failure and parasite drug resistance have, in some instances, also
      resulted in the increasing reluctance to over-prescribe synthetic anti
      microbials. Alternatively, there is now mounting evidence to suggest that some of
      the naturally derived, medium-chain, saturated fatty acids (MCSFAs) possess anti
      microbial and anti-parasitic properties. We have therefore examined the effects
      of four different fatty acids on G. duodenalis trophozoites in vitro.
      Cytotoxicity was determined using fluorescence, scanning and transmission
      electron microscopic techniques and standard cytotoxicity assays. Our studies
      have confirmed that the MCSFA, dodecanoic acid (C: 12) (common name: lauric
      acid), is anti-giardial, with an LD50 concentration comparable to that of
      metronidazole, the drug of choice in the treatment of giardiasis. Dodecanoic acid
      appeared to induce trophozoite death by accumulating within the parasite
      cytoplasm resulting in rupture of the cell membrane. This study has opened fresh
      avenues for development of natural drug therapy in which food supplementation may
      augment, or even replace, some of the standard chemotherapeutic agents presently
      employed in the treatment of giardiasis and possibly other infectious intestinal
      diseases.

PMID- 15991043
TI  - Dendritic cell expansion occurs in mesenteric lymph nodes of B10.BR mice infected
      with the murine nematode parasite Trichuris muris.
AB  - Dendritic cells (DCs) are a crucial element in the immune system and bridge
      innate and adaptive immunity. CD11c+ B220- DCs residing in Peyer's patches (PPs)
      have the ability to produce interleukin 10 (IL-10) and induce T helper (Th2)
      development. Evidence suggests that CD11c+ B220- DCs maintain the gut environment
      by suppressing Th1 responses with IL-10, resulting in a Th2-dominat gut
      environment. Th2 effectors are required for protection against the murine
      nematode parasite Trichuris muris, and thus CD11c+ B220- DCs may be involved in
      the induction of Th2 cells in T. muris infection. In the present study, the
      kinetics of CD11c+ B220- DCs were analyzed in mesenteric lymph nodes of B10.BR
      mice infected with the E-J isolate of T. muris, and the cellular expansion of
      CD11c+ B220- DCs was also observed. As well, the DC expansion was consistent with
      the occurrence of worm expulsion augmented by IL-4 and IL-13. The evidence here
      suggests the involvement of CD11c+ B220- DCs in protective Th2 responses to T.
      muris infection.

PMID- 15991044
TI  - Cross protection studies with Eimeria maxima strains.
AB  - The purpose of this study was to determine whether differences in fecundity of
      Eimeria maxima isolates were related to their abilities to elicit cross
      protective immunity. Immunizations were initiated by low-dose gavages of
      sporulated oocysts to day-old broiler chicks under conditions that allowed
      parasite recycling, and chickens were challenged with homologous and heterologous
      strains. Immunization efficacies were measured using a protective index
      calculated from weight gain, gross lesion score, plasma carotenoid, and NO2- +
      NO3- data. A 4x4 cross- immunization study of four E. maxima strains (designated
      A-D) showed that strain A, which displayed the lower fecundity, provided no cross
      protection against the other three strains. Following several maintenance
      passages, the fecundity of strain A was increased to that of strain C, and
      infection with strain A oocysts was able to provide cross-immune protection
      against challenge with strain C. This study indicates that parasite fecundity is
      important in providing good immune stimulation, and should be carefully monitored
      when characterization of the unique immune potentials of Eimeria strains is
      undertaken.

PMID- 15991046
TI  - In vivo detection of metabolic changes by 1H-MRS in the DEN-induced
      hepatocellular carcinoma in Wistar rat.
AB  - PURPOSE: To investigate the serial changes of the hepatic metabolites in a
      chemical-induced rat model of hepatocellular carcinoma (HCC) in vivo by a
      clinical 1.5 T MR scanner. METHODS: Diethyl nitrosamine (DEN) induced HCC model
      rats (n=60) and control rats (n=20) were included. From week 7 to week 20 after
      DEN administration, every other week 10-12 animals (8-9 treated and 2-3 controls)
      were randomly scanned before being sacrificed. According to the pathologic
      changes, the whole process of tumorigenesis was divided into early and late
      periods (week 7-13 and week 14-20, respectively). The serial hepatic changes were
      tested by both routine MRI and single voxel 1H-MRS and compared with pathological
      results. Point resolved spectroscopy sequence (PRESS) was used for the location
      in MRS. The integrations of lipid- and choline-containing metabolites were
      calculated and analyzed. RESULTS: All of the listed tests were fully finished in
      66 rats (48 treated and 18 controls). Of the MRS curves, 65.2% (43/66) could be
      analyzed (mainly with resistant baseline with peaks appearing at right
      positions). From those qualified MRS curves, there were up to seven peaks which
      could be identified. The peaks of methylene lipids and methyl lipids were
      combined together in most cases and became the most notable component. The
      relative integrals of the combined lipid peak and that of the choline-containing
      compounds in different groups and stages were measured. Comparing with that of
      the controls of the same stage, the lipid of treated rats decreased in the late
      stage, and the choline-containing compounds increased in the same stage.
      Statistically significant differences were found (P<0.05) for the integrals of
      the lipid and the choline-containing metabolites between treated and controls in
      the late stage. CONCLUSIONS: Our initial studies for the integrals of the lipid
      compounds and the choline-containing metabolites might be useful for a better
      understanding of the metabolic activity of this DEN-induced rat HCC model.

PMID- 15991045
TI  - Entamoeba histolytica and Entamoeba dispar infections in cynomolgus monkeys
      imported into Japan for research.
AB  - Three hundred and three stool samples of cynomolgus monkeys (Macaca fascicularis)
      imported from China and the Philippines were examined for Entamoeba
      histolytica/Entamoeba dispar infections. Microscopy detected E. histolytica/E.
      dispar cysts in 41 samples. Positive rates were higher in the monkeys from China
      (37.5%) than in the monkeys from the Philippines (3.7%). PCR analysis of 25
      samples successfully cultured from the cysts demonstrated that 24 were E. dispar,
      one of the samples from China was E. histolytica. The one sample was also
      identified as E. histolytica by an antigen detection kit, although the monkey was
      asymptomatic and serology was negative. To our knowledge, this is the first
      report of E. histolytica isolation from cynomolgus monkeys based on the
      discrimination between E. histolytica and E. dispar.

PMID- 15991047
TI  - [Follicular drug reaction from cetuximab: a common side effect in the treatment
      of metastatic colon carcinoma].
AB  - Cetuximab belongs to a newly developed group of anti-cancer drugs, which have an
      inhibitory effect on the epidermal growth factor receptor (EGF-R). EGF-R plays a
      major role in the homeostasis of the epidermis and epidermal appendages. In
      addition, EGF-R is expressed on a variety of carcinomas of different origin and
      is thought to be partly associated with tumor progression. For this reason,
      inhibition of EGF-R seems a promising anti-cancer therapy, as shown in a few
      clinical trials. As a side effect of the therapy, a follicular rash often
      develops in the seborrheic areas; this cutaneous reaction is associated with
      longer survival. We present a typical case and discuss the important features of
      the follicular rash occurring after EGF-R inhibition.

PMID- 15991048
TI  - Detection and clinical implications of minimal residual disease in gastro
      intestinal cancer.
AB  - INTRODUCTION: Metastatic dissemination is an important factor for the prognosis
      of patients with gastro-intestinal cancer. Exact staging is crucial to determine
      appropriate multimodal therapeutic strategies. At present, the sensitivity of
      routinely performed diagnostic techniques is suboptimal for the detection of
      minimal residual disease (MRD) and occult metastases since the number of
      disseminated tumour cells (DTCs) is mostly marginal. To amend the verification of
      DTCs, immunohistochemical and molecular methods were applied to retrieve
      epithelial cell-specific proteins in non-epithelial tissue of different body
      compartments or fluids. Many groups have eagerly focussed on the identification
      of new markers and novel tests, yet specificity and sensitivity of these methods
      as well as robustness in the clinical setting are frequently missing. MATERIALS
      AND METHODS: This review critically evaluates the prognostic impact of MRD in
      patients with pancreatic, colorectal and gastric cancer by outlining those
      studies showing diagnostic results of DTC detection in lymph nodes, bone marrow,
      venous blood and peritoneal lavage, some of which present novel strategies.
      CONCLUSION: The analysed data concerning MRD in gastro-intestinal cancers reveal
      that results are undesirably heterogeneous. From a critical point of view, many
      clinical studies missed their chance because of small cohort size; moreover,
      methodological standardisation is generally lacking. On the other hand, the very
      encouraging results achieved so far, together with the comprehensive analyses of
      a few research groups, foster the prediction that DTC/MRD issues will soon expand
      the standard TNM classification.

PMID- 15991049
TI  - [Experiences with surgical management of facial basal cell carcinoma and
      procedures for plastic reconstruction].
AB  - BACKGROUND: No recurrences and optimal aesthetic outcomes after R0 resection and
      plastic reconstruction of the face are the goals in the surgical treatment of
      basal cell carcinoma. The aim of this study was to evaluate recurrence rates and
      to evaluate different reconstructive techniques. PATIENTS AND METHODS: This study
      included 205 follow-up patients undergoing R0 resection of primary basal cell
      carcinoma and facial skin reconstruction between 1998 and 2002; data were
      analyzed retrospectively. RESULTS: The most frequent locations of basal cell
      carcinoma were the nasal (40.5%) and orbital (22.9%) regions. The rate of
      recurrence after 2.5 years (6 months-5 years) was 7.3%. Local flaps, full
      thickness skin grafts, and sliding flaps were usually performed; indications for
      split-thickness skin grafts were rare. Disturbances of sensation were found in
      only 3.6% of the sliding flaps and in 11.7% of the local flaps, but 22.7% in full
      thickness and 38.7% in split-thickness skin grafts. The aesthetic outcome,
      evaluated by clinical inspection and a patient satisfaction score, was classified
      as "unobtrusive" and "good or excellent" for 88.4% of local flaps, 92.6% of
      sliding flaps, but only for 66.4% of full-thickness and 54% of split-thickness
      skin grafts. CONCLUSION: Local flaps and sliding flaps result in better aesthetic
      and neurological outcomes after reconstruction of facial skin regions. Skin
      grafts have their indications as an alternative procedure in cases of critical
      indications for flaps.

PMID- 15991050
TI  - Human melanomas express functional P2 X(7) receptors.
AB  - Adenosine 5'-triphosphate is known to function as a potent extracellular
      messenger, producing its effects via a distinct family of cell surface receptors.
      Different receptor subtypes have been shown to modulate different cellular
      functions such as proliferation, differentiation and apoptosis. We have
      investigated the functional expression and apoptotic action of the P2 X (7)
      receptor in human malignant melanoma tissue and cells. Incubation of cells with
      the potent P2 X (7) receptor agonist 2'-3'-O-(4-benzoyl-benzoyl) adenosine 5'
      triphosphate leads to a decrease in cell number, which is dose-dependent and
      reversible by the antagonist 1-N,O-bis-[5-isoquinoline-sulfonyl]-N-methyl-L
      tyrosyl)-4-phenyl-piperazine. Synthesis of the P2 X(7) receptor by these cells
      has been established by reverse transcriptase-polymerase chain reaction,
      immunohistochemistry, immunocytochemistry and cellular accumulation of the
      fluorescent DNA-binding dye YO-PRO-1. The P2 X(7) receptors have been shown to
      mediate apoptotic actions of extracellular nucleotides and represent a novel
      target for melanoma therapy.

PMID- 15991051
TI  - Role of biofilms in neurosurgical device-related infections.
AB  - Bacterial biofilms have recently been shown to be important in neurosurgical
      device-related infections. Because the concept of biofilms is novel to most
      practitioners, it is important to understand that both traditional pharmaceutical
      therapies and host defense mechanisms that are aimed at treating or overcoming
      free-swimming bacteria are largely ineffective against the sessile bacteria in a
      biofilm. Bacterial biofilms are complex surface-attached structures that are
      composed of an extruded extracellular matrix in which the individual bacteria are
      embedded. Superimposed on this physical architecture is a complex system of
      intercellular signaling, termed quorum sensing. These complex organizational
      features endow biofilms with numerous microenvironments and a concomitant number
      of distinct bacterial phenotypes. Each of the bacterial phenotypes within the
      biofilm displays a unique gene expression pattern tied to nutrient availability
      and waste transport. Such diversity provides the biofilm as a whole with an
      enormous survival advantage when compared to the individual component bacterial
      cells. Thus, it is appropriate to view the biofilm as a multicellular organism,
      akin to metazoan eukaryotic life. Bacterial biofilms are much hardier than free
      floating or planktonic bacteria and are primarily responsible for device-related
      infections. Now that basic research has demonstrated that the vast majority of
      bacteria exist in biofilms, the paradigm of biofilm-associated chronic infections
      is spreading to the clinical world. Understanding how these biofilm infections
      affect patients with neurosurgical devices is a prerequisite to developing
      strategies for their treatment and prevention.

PMID- 15991053
TI  - Anti-Listeria monocytogenes bacteriocin-like inhibitory substances from
      Enterococcus faecium UQ31 isolated from artisan Mexican-style cheese.
AB  - Artisan fresh Mexican-style cheeses are commonly made from raw milk that provides
      not only rich flavors, but also a diversity of associated lactic acid bacteria
      (LAB) strains. Enterococcus faecium UQ31 was isolated from panela cheese and
      produced bacteriocin-like inhibitory substances (BLIS) with a strong anti
      Listeria activity. A modified pH-mediated adsorption-desorption purification
      process resulted in (after SDS-PAGE) two bands showing antimicrobial activities,
      where most of the activity corresponded to the band with an estimated molecular
      weight of 7.5 kDa. The BLIS produced by E. faecium UQ31 were heat resistant,
      stable at ambient storage conditions, and active in the pH range 5--9. The BLIS
      antimicrobial activities were detected during logarithmic growth phase and
      remained constant until the end of incubation time (19 h). These BLIS showed a
      wide anti-Listeria monocytogenes spectra. The E. faecium UQ31 strain or their
      BLIS represent a promising potential as antimicrobial food preservatives.

PMID- 15991052
TI  - Anaerobic growth of Candida albicans does not support biofilm formation under
      similar conditions used for aerobic biofilm.
AB  - C. albicans is an opportunistic fungus causing life-threatening systemic
      infections particularly in immunocompromised individuals. The organism is a
      commensal in humans and grows either aerobically, e.g., the oral cavity, or
      anaerobically, e.g., the gut. We studied anaerobic growth of C. albicans in a
      defined yeast nitrogen base dextrose medium after adaptation and subculturing in
      an anaerobic chamber. At 37 degrees C in suspension culture, much slower growth
      was observed anaerobically with a generation time of 248 min compared to 98 min
      for aerobic growth. Although the organism grew well on solid medium, shaking
      increased the growth rate in suspension culture at 37 degrees C. Growth was
      enhanced at acidic pH compared to neutral or alkaline pH. Cells grown
      anaerobically produced hyphae, but did not produce biofilm on plastic surface or
      denture acrylic under either static conditions or with mild shaking, conditions
      that support aerobic biofilm formation.

PMID- 15991054
TI  - A new insertion variant, IS231I, isolated from a mosquito-specific strain of
      Bacillus thuringiensis.
AB  - A new insertion variant belonging to the family IS231, designated IS231I, was
      isolated from a mosquito larvicidal strain of the Bacillus thuringiensis serovar
      sotto (H4ab). IS231I was 1653 bp long and delimited by two 20 bp inverted repeats
      with one mismatch, flanked by two perfect 11 bp direct repeats. The element
      contained a single open reading frame (ORF) encoding 478 amino acids and five
      conserved domains: N1, N2, N3, C1, and C2. The 5' noncoding region upstream of
      the ORF, presumed to form a stable stem-and-loop structure, was highly conserved
      in IS231I. The secondary structure conformation had a deduced free energy
      (DeltaG=25 degrees C) of -17.2 kcal/mol. Comparison of the IS231I amino acid
      sequence with those of the 10 existing IS variants revealed that the new variant
      shares 89% identity with IS231A and IS231B, 65-66% with IS231M and IS231N, and
      38% with IS231W.

PMID- 15991055
TI  - Cloning, sequence analysis, and expression of the gene encoding Sphingomonas
      paucimobilis FP2001 alpha-L -rhamnosidase.
AB  - The gene (rhaM) encoding the alpha-L-rhamnosidase of Sphingomonas paucimobilis
      FP2001 was cloned, sequenced, and expressed in Escherichia coli. The rhaM
      consisted of 3,354 nucleotides and had a promoter and Shine-Dalgarno sequences
      typical in bacteria. The rhaM encoding a protein (Rham) deducted from the
      sequence consisted of 1,117 amino acids and had a putative signal peptide of 25
      amino acids. Rham has no similarity to other known rhamnosidases. Rham has a
      sugar-binding domain of glycoside hydrolase family 2, which has been well
      conserved in beta-glucuronidase, beta-mannosidase, and beta-galactosidase, in its
      C-terminal region. Rham is possibly a member of a new bacterial subfamily in
      glycoside hydrolase family 78 (alpha-L-rhamnosidase). RT-PCR analysis of rhaM
      mRNA indicated that the induction of alpha-L-rhamnosidase by the addition of L
      rhamnose occurred on the transcriptional level.

PMID- 15991056
TI  - Characterization and transcription of the genes involved in butyrate production
      in Butyrivibrio fibrisolvens type I and II strains.
AB  - The genes in Butyrivibrio fibrisolvens that encode the enzymes involved in
      butyrate production were sequenced. In a type I strain (ATCC 19171(T)), the genes
      coding for the enzymes that catalyze the conversion from acetyl-CoA to butyryl
      CoA, thl (thiolase), crt (crotonase), hbd (beta-hydroxybutyryl-CoA
      dehydrogenase), bcd (butyryl-CoA dehydrogenase), etfB (electron transfer
      flavoprotein [ETF]-beta), and etfA (ETF-alpha), were found to be clustered and
      arranged in this order. A type II strain (ATCC 51255) had the same clustered
      genes with the same arrangement, except that crt was not present in the clustered
      genes. The deduced amino acid sequences of these enzymes did not greatly differ
      between the two strains, and even between B. fibrisolvens and clostridia. Amino
      acid identity appeared to be higher within the same type than between types I and
      II. The clustered genes were shown to be cotranscribed, and constitutively
      transcribed without being affected significantly by culture conditions.

PMID- 15991057
TI  - Production of the long-chain alcohols octanol, decanol, and dodecanol by
      Escherichia coli.
AB  - As a follow-up to earlier studies on the emission of long-chain alcohols from
      broth cultures of Gram-negative enteric bacteria, E. coli was examined for the
      production of 1-octanol, 1-decanol, and 1-dodecanol. Ten strains of E. coli
      cultured in tryptic soy broth were assayed for volatile metabolites using solid
      phase microextraction. Long-chain alcohols were produced by all strains with 1
      decanol predominating with production ranging from 23.6 ng mL(-1) to 148 ng mL(
      1). The production of long-chain alcohols followed the onset of the exponential
      growth phase of the broth culture. Doubling the concentration of glucose (5 g L(
      1)) in the broth had no effect on the concentration of long-chain alcohols
      produced. Addition of octanoic, decanoic, or dodecanoic acids (as K(+) salts) to
      the broth (100 mg L(-1)) markedly increased the production of the corresponding
      alcohols by E. coli, ranging from a 13-fold increase for decanol to a 51-fold
      increase for dodecanol. However, decanol remained the predominant alcohol
      detected in all assays. These neutral volatile alcohols may have application as
      vapor-phase indicators for certain classes of bacteria, particularly, Gram
      negative enteric bacteria.

PMID- 15991058
TI  - Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of
      the anal region: long-term results of 101 patients.
AB  - PURPOSE: This study was designed to assess the long-term results following
      radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate
      the impact of tumor location on response, survival, and colostomy-free survival.
      PATIENTS AND METHODS: Between 1985 and 2001, a total of 101 patients with anal
      carcinoma were registered for curative treatment, of whom 77 had involvement of
      the anal canal alone, 10 cases had extension into the perianal skin, and 14
      patients had pure anal margin tumors. Small tumors of the anal margin were not
      included since they were treated by surgical excision only. Among the 101
      patients were 74 women and 27 men with a median age of 62 (range, 26-84) years. T
      categories (International Union against Cancer) were T1 (15), T2 (36), T3 (34),
      and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30
      presented with involved regional nodes. Radiation treatment was directed to the
      primary tumor region and to the inguinal, perirectal, and internal iliac nodes
      using a three-field to four-field box technique with 10MV photons up to a total
      dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by
      interstitial or external radiation depending on circumferential extension of the
      residual tumor. All patients were scheduled for simultaneous chemotherapy with
      two cycles of 5-fluorouracil at a dose of 1000 mg/m (2)/day as 120 hours of
      continuous intravenous infusion on Days 1 to 5 and 29 to 33 and mitomycin C at 10
      mg/m (2)/day on Days 1 and 29. Median follow-up time was was 7.5 (range, 1-16)
      years. RESULTS: Overall survival and colostomy-free survival rates for patients
      with anal canal cancer were 75 percent and 87 percent at five years,
      respectively. Patients with anal margin cancer had a less favorable outcome with
      five-year-overall and colostomy-free survival rates of 54 percent and 69 percent,
      respectively. After correction for imbalance between anal canal and anal margin
      tumors, i.e., exclusion of T1 tumors of the anal canal, difference in overall
      survival remained significant (73 percent vs. 54 percent, P = 0.01). Following
      multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age
      (P = 0.003), and dose intensity of chemotherapy (< or =75 percent vs. >75
      percent, P = 0.03) remained independent significant factors for overall survival.
      Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free
      survival. CONCLUSIONS: With colostomy-free survival rates around 85 percent, long
      term treatment results for anal canal carcinoma have reached a satisfactory
      level. However, patients with larger lesions of the perianal skin are at high
      risk for locoregional recurrence and possible treatment intensification in this
      subgroup seems desirable.

PMID- 15991059
TI  - Utility of 2-fluoro-2-deoxy-D-glucose positron emission tomography in managing
      patients of colorectal cancer with unexplained carcinoembryonic antigen elevation
      at different levels.
AB  - PURPOSE: Serum carcinoembryonic antigen elevation without detectable relapse
      during colorectal cancer follow-up presents a challenge. This study was designed
      to evaluate the utility of fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose
      positron emission tomography in colorectal cancer patients with unexplained
      carcinoembryonic antigen elevation at different levels. METHODS: Thirty-seven
      colorectal cancer patients referred for positron emission tomography after
      primary surgery who had serum carcinoembryonic antigen levels >5 ng/ml and
      negative or equivocal conventional imaging studies were analyzed. Patient status
      was determined by histopathology and/or clinical follow-up. Grouping as disease
      free, potentially resectable, or advanced disease was performed. The management
      impact was defined as the percentage of patients with a true-positive positron
      emission tomography result. RESULTS: The sensitivity, specificity, and accuracy
      of positron emission tomography for relapse detection were 89, 89, and 89
      percent, respectively. The management impact was 68 percent. In 24 patients with
      carcinoembryonic antigen levels <25 ng/ml, positron emission tomography helped
      correct patient grouping in 20 patients (83 percent), including 8 in the disease
      free group, 5 in the potentially resectable group, and 7 in the advanced-disease
      group. In 13 patients with carcinoembryonic antigen levels >25 ng/ml, positron
      emission tomography identified 8 patients in the advanced-disease group and 1
      patient in the potentially resectable group but missed 2 patients with relapse
      and undergrouped 2 patients in the advanced-disease group as potentially
      resectable. CONCLUSIONS: 2-fluoro-2-deoxy-D-glucose positron emission tomography
      can help triage patients for appropriate management with unexplained
      carcinoembryonic antigen elevation <25 ng/ml. For patients with unexplained
      elevation of carcinoembryonic antigen >25 ng/ml, the utility of positron emission
      tomography is mainly to confirm the presence of advanced disease and occasionally
      to identify potentially resectable lesions.

PMID- 15991060
TI  - Lidocaine anal block limits autonomic dysreflexia during anorectal procedures in
      spinal cord injury: a randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE: Autonomic dysreflexia is a common and potentially dangerous hypertensive
      response to stimulation below the level of injury that occurs in patients with
      spinal cord injury at T6 or above. Rectosigmoid distention and anal manipulation
      are among the stimuli that may precipitate autonomic dysreflexia. Instillation of
      topical local anesthetic into the rectum is the recommended prophylaxis against
      autonomic dysreflexia of anorectal origin. However, a previous randomized, double
      blind, placebo-controlled trial showed that topical lidocaine in the rectum does
      not blunt the autonomic dysreflexia response to anorectal procedures. The purpose
      of this study was to determine whether lidocaine anal sphincter block would be
      effective in limiting anorectal procedure-associated autonomic dysreflexia.
      METHODS: We enrolled patients with chronic, complete spinal cord injury above T6,
      who were having anorectal procedures (flexible sigmoidoscopy and/or anoscopic
      hemorrhoid ligation). In a double-blind fashion, patients were randomized for
      intersphincteric anal block with 1 percent lidocaine or normal saline (placebo)
      before the procedure. Blood pressure was measured before, during, and after the
      block and procedure. RESULTS: Thirteen patients received lidocaine, and 13
      received placebo. The groups were similar in age, level of injury, duration of
      spinal cord injury, type of procedure, and procedure duration. The mean maximal
      systolic blood pressure increase for the lidocaine group was 22 +/- 14 mmHg,
      significantly lower than the placebo group's 47 +/- 31 mmHg (P = 0.01).
      CONCLUSIONS: Lidocaine anal block significantly limits the autonomic dysreflexia
      response in susceptible patients undergoing anorectal procedures.

PMID- 15991061
TI  - Ileal pouch-anal anastomosis-vaginal fistula: a review.
AB  - BACKGROUND: Fistula between an ileal pouch and the vagina is an uncommon
      complication of ileal pouch-anal anastomosis. Its optimal management has not been
      determined because of its low incidence. METHODS: The literature describing such
      fistulas was reviewed to determine the incidence, cause, and appropriate
      investigation and repair of these lesions. A literature search was performed with
      the PubMed, MEDLINE, and EMBASE databases. Through this search we located English
      language articles from 1970 to 2003 on pouch-vaginal fistulas following ileal
      pouch-anal anastomosis. References from these articles were searched manually for
      further references. RESULTS AND CONCLUSION: Pouch-vaginal fistula occurs in 6.3
      (range, 3.3-15.8) percent of female patients with an ileal pouch-anal
      anastomosis. Sepsis and technical factors are the most common contributors. It is
      the cause of considerable morbidity. Management depends on the level of the
      fistula, the amount of pelvic scar tissue, and previous treatments. An algorithm
      for surgical treatment is suggested.

PMID- 15991062
TI  - Reoperation for intraluminal rectal cancer recurrence.
AB  - PURPOSE: Following curative resection for rectal cancer, approximately 5 percent
      of locoregional recurrences occur intraluminally, presumably because of tumor
      exfoliation during the initial operation. The rate of resectability, subsequent
      locoregional control, and survival in patients with isolated intraluminal
      recurrence have not been well studied. METHODS: From 1994 to 2003, nine patients
      (seven males; median age, 68 years) with isolated intraluminal rectal cancer
      recurrence were treated for cure at our center. RESULTS: Initial procedures
      performed were four high anterior resections and five low anterior resections for
      tumors having a median distance from the anal verge of 12.5 (range, 7.5-16) cm.
      Median resected distal margin was 2.5 (range, 1.2-4.0) cm. Original tumor staging
      was T2 N0 M0 in three, T3 N0 M0 in three, T3 N1 M0 in one, and T3 N2 M0 in two.
      Median time between primary resection and intraluminal recurrence was 21 (range,
      8-53) months. Intraluminal recurrence distal to the anastomosis occurred in three
      of nine patients and anastomotic recurrence occurred in six of nine patients.
      Pathologically clear margins were obtained in all patients at the time of
      curative re-resection. Following re-resection, patients were followed for a mean
      of 30 (range, 6-59) months. No patient has developed locoregional recurrence to
      date or to the time of patient death. Six of nine patients are alive and disease
      free with a median follow-up of 34.5 (range, 6-59) months. One patient died
      disease-free at 35 months. One patient died from pulmonary metastases 30 months
      postoperatively and another patient developed liver metastasis 11 months
      postoperatively. CONCLUSION: Endoscopic surveillance following sphincter-sparing
      rectal cancer resection is warranted as re-resection for intraluminal recurrence
      can result in locoregional control and significant disease-free survival.

PMID- 15991065
TI  - Recurrent sigmoid volvulus in pregnancy: report of a case and review of the
      literature.
AB  - Intestinal obstruction caused by sigmoid volvulus is extremely rare during
      pregnancy; only 73 cases have been reported worldwide. A case report of recurrent
      sigmoid volvulus in a 22-year-old pregnant Saudi female and a review of the
      literature are presented. Despite a previous sigmoidopexy in another institution,
      colonoscopic detortion and rectal tube decompression was successful until after
      delivery when sigmoid colectomy was performed. From this case, we propose a
      treatment option based on the absence or presence of peritonitis and gestational
      age is suggested. In the first trimester, nonoperative procedure using
      colonoscopic detorsion and rectal tube decompression is recommended until the
      second trimester when sigmoid colectomy is performed for recurrent cases. In the
      third trimester, the treatment is nonoperative until fetal maturity and delivery
      when sigmoid colectomy is performed. Sigmoid volvulus complicating pregnancy is
      an uncommon and potentially serious condition and should be recognized as a
      surgical emergency. Prompt surgical intervention is necessary to minimize
      maternal and fetal morbidity and mortality.

PMID- 15991064
TI  - Low allele frequency of MLH1 D132H in American colorectal and endometrial cancer
      patients.
AB  - PURPOSE: Hereditary nonpolyposis colon cancer is caused by mutations in DNA
      mismatch repair genes, predominantly MLH1 and MSH2. Classic MLH1 mutations cause
      an approximately 20-fold increase in colorectal cancer susceptibility. Recently,
      we identified a hypomorphic allele, MLH1 D132H , which impairs, but does not
      completely eliminate the function of MLH1 in tumor suppression. MLH1 D132H
      confers an approximately fivefold increase in colorectal cancer susceptibility
      and was first described in a cohort of Israeli colorectal cancer patients, with
      an estimated allele frequency of 1.3 percent. Because MLH1 D132H has only
      recently been described, the ethnic distribution of this risk allele is not well
      understood. This study was undertaken to determine both the frequencies of this
      risk allele in ethnic groups outside of Israel and whether families harboring
      this mutation have susceptibility to extracolonic cancers in the hereditary
      nonpolyposis colon cancer spectrum. METHODS: We genotyped two independent
      cohorts: 629 population-based colorectal cancer patients ascertained from clinics
      in Orange, Imperial, and San Diego Counties, and 515 endometrial cancer patients
      ascertained from gynecologic oncology clinics in the Midwestern United States.
      RESULTS: MLH1 D132H was not detected in either study cohort, which together
      totaled more than 1,100 American colorectal cancer and endometrial cancer
      patients. CONCLUSIONS: The MLH1 D132H risk variant has significantly lower allele
      frequency in American compared with Israeli cancer patients and, alone, is
      unlikely to explain significant amounts of American sporadic colorectal cancer or
      uterine cancer susceptibility. Genetic testing for the MLH1 D132H allele
      exclusively is therefore unlikely to be cost effective for genetic risk
      assessment in American population-based and clinic-based colorectal cancer and
      endometrial cancer patients.

PMID- 15991066
TI  - Laparoscopic-assisted rectal foreign body removal: report of a case.
AB  - PURPOSE: Rectal foreign bodies are not an uncommon presentation to the emergency
      department. Frequently they can be removed in the department through the
      transanal approach. However, this often is not well tolerated by the patient or
      can force the foreign body more proximal. We present a case of a difficult rectal
      foreign body in an obese patient that was successfully removed transanally in the
      operating room with laparoscopic assistance. METHODS: Under general anesthesia,
      with the patient in Trendelenburg position, laparoscopy was used to push the
      rectal foreign body from above while it was removed transanally from below. This
      was performed with one 10-mm and two 5-mm incisions. RESULTS: The foreign body
      was successfully removed transanally with laparoscopic assistance, and the
      patient was discharged within 12 hours from the operation. CONCLUSIONS: The
      laparoscopic approach to assist in rectal foreign body removal is a good
      treatment choice for difficult cases. It allows for easy removal, detection of
      rectal injury, and early discharge.

PMID- 15991067
TI  - Inverted colonic mucosal lesion: is this a new entity of colon lesion? Report of
      a case.

PMID- 15991068
TI  - Guided imagery and relaxation in conventional colorectal resections: a
      randomized, controlled, partially blinded trial.
AB  - PURPOSE: The aim of this study was to investigate whether brief psychologic
      interventions to reduce perioperative stress may improve the postoperative course
      of patients undergoing abdominal surgery. METHODS: We used a randomized,
      controlled, partially blinded trial to evaluate the differential effectiveness of
      two brief psychologic interventions (guided imagery and progressive muscle
      relaxation) on analgesic requirement, pain perception, pulmonary function,
      duration of postoperative ileus, and fatigue after conventional resection of
      colorectal carcinoma in elderly cancer patients. RESULTS: Sixty patients (20
      guided imagery, 22 relaxation, 18 control) were evaluated. Acceptance of the
      brief psychologic interventions was high and 90 percent of the patients indicated
      that they would recommend it to other patients. Analgesic consumption (P = 0.6)
      and subjective pain intensity at rest (P = 0.3) and while coughing (P = 0.3) were
      not different between groups. Recovery of pulmonary function, duration of
      postoperative ileus, and subjective postoperative fatigue were also not
      influenced. When the data from intervention groups were pooled, again no benefits
      were detected compared with the control group. CONCLUSIONS: Brief psychologic
      interventions such as guided imagery and relaxation yielded a very positive
      patient response but did not show a clinically relevant influence on the
      postoperative physiologic course of elderly patients undergoing conventional
      resections of colorectal cancer.

PMID- 15991069
TI  - Progressive increase of bowel wall thickness is a reliable indicator for surgery
      in patients with adhesive small bowel obstruction.
AB  - PURPOSE: The aim of this study was to determine whether progressive increase of
      bowel wall thickness during nonoperative treatment is a reliable indicator for
      surgery in patients with adhesive small bowel obstruction. METHODS: The study
      consisted of a prospective case series of 121 patients with adhesive small bowel
      obstruction who underwent an abdominal ultrasonographic examination. The results
      of ultrasonographic examinations were classified into two groups according to the
      presence (Group I) or absence (Group II) of bowel wall thickening. Bowel wall
      thickening was recognized as a visible small bowel wall > or =3 mm in width as
      seen by ultrasonographic examination. The findings of subsequent ultrasonographic
      examinations taken 24 hours later were compared with those taken at admission.
      Surgery was determined based on the presence of any toxic signs or the failure of
      nonoperative treatment. The number of patients who had successful nonoperative
      treatment, the number of patients who underwent surgeries, and the number of
      complications in each group were calculated to correlate with the
      ultrasonographic findings. RESULTS: There are 49 and 72 patients in Groups I and
      II, respectively. The number of patients who had successful nonoperative
      treatment and number of patients who underwent surgeries in Group I are 40 (81.6
      percent) and 9 (18.4 percent) and in Group II the numbers are 68 (94.4 percent)
      and four (5.6 percent), respectively (P = 0.036). All 12 (100 percent) patients
      with progressive increase of bowel wall thickness underwent surgery. Progressive
      increase of bowel wall thickness as an indicator for surgery has a sensitivity of
      92.3 percent (95 percent confidence interval, 62.1-99.6 percent) and a
      specificity of 100 percent (95 percent confidence interval, 95.7-100 percent).
      CONCLUSIONS: Patients with initial bowel wall thickening have a higher incidence
      of surgery, and progressive increase of bowel wall thickness that appears 24
      hours later is a reliable indicator for surgery in patients with adhesive small
      bowel obstruction.

PMID- 15991071
TI  - [Forty-sixth Congress of the German Society for Pneumology, 16-19 Mar in Berlin-
      new findings in pneumology].

PMID- 15991070
TI  - The dark side of double-stapled transanal rectal resection.

PMID- 15991072
TI  - [CT-Guided transthoracic aspiration of peripheral pulmonary nodules with a
      special bioptic needle].
AB  - Peripheral pulmonary nodules are difficult to reach bronchoscopically, so for a
      long time it has been tried, by the use of imaging techniques like X-ray,
      ultrasound and computed tomography, to aspirate these nodules for exact
      histological diagnosis. The computed tomography offers the best spatial
      orientation for methodical reasons, thus this technique is performed increasingly
      and with great accuracy in pulmonary lesions. Complications like bleeding into
      lung parenchyma or small pneumothorax after aspiration can be detected easier by
      computed tomography. In this study we evaluated the use of a special bioptic
      technique with the AUTOVAC(R) needle in 30 cases. Causing low parenchymal damage
      to the lung, this bioptic needle enables extraction of representative tissue
      samples for further pathological examination. In 21 of 30 (70 %) cases the
      histological specimen led to the diagnosis of malignancy, but 8 of those
      malignant specimen could have been verified as primary or secondary malignancy by
      using additional immunocytochemical techniques. In 2 of 30 cases (7 %) harmless
      hemorrhage into lung parenchyma occured after aspiration. In another 4 of 30 (13
      %) cases pneumothorax occurred, requiring chest tube placement. The ct-guided
      lung biopsy with the AUTOVAC(R) needle represents a safe, low resilient
      diagnostic tool to obtain large tissue samples of specimen in good quality. Even
      in patients with compromised lung function because of severe chronic obstructive
      lung disease and/or emphysema, the described aspiration technique can be
      performed, if at the moment of aspiration procedure a pneumologist with
      corresponding equipment and trained medical staff is present, in order to place a
      chest tube in case of pneumothorax.

PMID- 15991073
TI  - [Pulmonary megakaryocyte-embolism in contact with osteomyelofibrosis].

PMID- 15991074
TI  - [Pulmonary sarcoidosis].

PMID- 15991075
TI  - [Cystic fibrosis modifying genes].
AB  - Cystic fibrosis is a common autosomal recessive disease that is caused by
      mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
      The CFTR gene encodes a membrane-bound chloride ion channel. CFTR gene mutations
      cause alterations in fluid and salt secretion of various tissues. The CF
      phenotype is highly variable even in siblings and twins carrying the same CFTR
      mutations. The course of CF pulmonary disease is modulated by both environmental
      and genetic factors independent of CFTR. This review summarises association
      studies that focused on disease modifier genes in CF. Understanding the molecular
      and cellular basis of the genotype-phenotype associations will help to better
      understand the disease and to identify new targets for therapeutic interventions
      in CF.

PMID- 15991076
TI  - [Occupational allergies to papain].
AB  - Occupational exposure against dusts of plant, bacterial, mould, and animal
      enzymes is long known to be associated with a high risk of specific
      sensitization. The present evaluation of literature data confirms that this is
      also true for papain. This frequently used industrial protease is derived from
      papaya (Carica papaya). Several cases of specific airway sensitization caused by
      papain are verified by a number of case reports and cross sectional studies. As
      symptoms, results of skin prick tests, detection of specific IgE-antibodies and
      results of specific bronchoprovocation tests are consistent, an immunologic
      mechanism can be assumed.

PMID- 15991077
TI  - [Importance of animal models as a medium between research and the clinic].

PMID- 15991078
TI  - [Pulmonary infection models--7. Workshop on work crises "Comparative pathology
      and pathophysiology of the respiratory system" of the German Veterinary Medical
      Society in co-operation with the sections of infectious diseases and tuberculosis
      and cell biology of the German Society of Pneumology on 17 Mar 2005 om Berlin].

PMID- 15991079
TI  - [Models of pulmonary infections in large animals--species specific differences].

PMID- 15991080
TI  - [Morphology of pulmonary infection models in various species and their value].

PMID- 15991081
TI  - [Pneumococcal pneumonia in a mouse model].

PMID- 15991082
TI  - [Pathogen-induced immunomodulation through toll-like receptors in an animal
      models].

PMID- 15991083
TI  - [Pulmonary infections in human human lung tissue models].

PMID- 15991084
TI  - [Model of meconium aspiration in piglets].

PMID- 15991085
TI  - [Sensitive FISH--fluorescence in situ hybridization in microbiological
      diagnosis].

PMID- 15991086
TI  - Histological investigation of liposuctioned fat for injection laryngoplasty.
AB  - PURPOSE: There are a few injectable biomaterials used in vocal-fold-augmentation
      surgery. In this study, liposuctioned autologous fat, used as the injection
      material, was investigated histologically. MATERIALS AND METHODS: Liposuctioned
      fat, which was harvested from 13 patients during injection laryngoplasty, was
      examined by light and electron microscopy. RESULTS: The cell membranes of most of
      the liposuctioned fat had not been damaged during harvesting and microinjection
      by our method. The harvested liposuctioned fat was a group of unilocular fat
      cells. Each cell was surrounded by a meshwork of fine reticular fibers. The cells
      were spherical and about 30 to 130 microm in diameter. The cells size and density
      were different from individual to individual. The diameters of liposuctioned fat
      cells were correlated with the body mass index. Dense and small fat cells were
      able to maintain graft volume. Sparse and large fat cells tended to not be able
      to maintain graft volume. There was little proliferation of unilocular fat cells,
      which were not able to maintain graft volume. CONCLUSION: The structure
      consisting of a unilocular cell, containing a single droplet of lipid, surrounded
      by a meshwork of delicate reticular fiber is one of the reasons why autologous
      fat has viscous properties similar to those of human lamina propria. Autologous
      fat was not damaged by our harvesting and microinjection method. The size,
      density and proliferation of fat cells, and ground substance around them may be
      related to resorption and a decrease in surviving graft volume.

PMID- 15991087
TI  - Labyrinthitis secondary to experimental otitis media.
AB  - PURPOSE: Analysis of labyrinthitis in a model of otitis media. MATERIALS AND
      METHODS: Morphologic study in 20 Wistar rats in which otitis media was induced by
      transbullar inoculation of Pseudomonas aeruginosa with obstruction of the
      eustachian tube. RESULTS: Seventy percent of rats showed vestibular signs.
      Histologic changes ranged from nonaffected labyrinths to suppurative
      labyrinthitis. CONCLUSIONS: Dissemination of infection probably occurs through
      round window membrane. A thinner round window membrane typical of rodents would
      be the reason for a more severe clinical and morphologic picture in rats when
      compared to human beings.

PMID- 15991088
TI  - Management of facial paralysis in temporal bone fractures: a prospective study
      analyzing 11 operated fractures.
AB  - OBJECTIVE: This study was instituted to evaluate patients operated on for
      traumatic facial paralysis. STUDY DESIGN: A prospective study and literature
      review. MATERIALS AND METHODS: Between 1996 and 2001, 10 patients with 11
      temporal bone fractures resulting in facial paralysis, who were treated by
      surgical exploration, were handled. One patient had bilateral facial paralysis
      because of a bilateral temporal bone fracture. All patients had immediate facial
      paralysis after trauma. The sample included 7 males and 3 females, aged between 8
      and 43 years. RESULTS: Of the 11 fractures, 7 (63%) were longitudinal and 4 (37%)
      were mixed type. There were no transverse fractures. The longitudinal fractures
      were operated on by the middle cranial fossa (MCF) approach, whereas the mixed
      fractures were operated on by using a combined approach, consisting of both MCF
      and transmastoid approaches. The first neurotologic examination and
      electrophysiological evaluation of the patients were carried out at the earliest
      5 days and at the latest 50 days (mean, 25.6 days). The decision for surgery
      based mainly on electroneurography (ENoG) was possible only in one fracture. In
      the remaining 10 fractures, the decision for surgery was based mainly on the high
      resolution computed tomography (HRCT), taking into account that electromyography
      (EMG) showed no regeneration potentials. The timing of the surgical intervention
      ranged from 14 to 75 days (mean, 37.9 days). During the operation, fibrosis at
      the geniculate ganglion was seen in 5 fractures, impingement of the facial nerve
      by bone spicules at the geniculate ganglion in 2 fractures, disruption or
      laceration at the origin of major superficial petrosal nerve also in 2 fractures,
      and edema around the geniculate ganglion, which is considered a mild form of
      injury, seen in only 2 fractures. Five fractures showed House-Brackmann (HB)
      grade 1, 4 patients showed HB grade 2, and 2 patients showed HB grade 3 facial
      recovery. There were no hearing deterioration or permanent complications related
      with the procedures. CONCLUSIONS: It is rarely possible to see the patients with
      traumatic facial paralysis in the early period and thus to perform ENoG in the
      critical 6 days after facial paralysis. HRCT, with the contribution of EMG and
      clinical judgment, has the greatest impact in decision making in patients seen
      late. On the basis of the facial outcomes observed in the present prospective
      surgical series, the recovery of satisfactory facial nerve function could be
      achieved, regardless of timing of surgery performed, within the first 3 months
      after the onset of paralysis. This study demonstrates that unless there is a
      disruption of the main trunk, necessitating primary end-to-end anastomosis or
      grafting, the type of injury does not have any clear effect on the facial
      outcome, as long as appropriate surgical management is applied.

PMID- 15991089
TI  - Prevalence of gastroesophagopharyngeal acid reflux events: an evidence-based
      systematic review.
AB  - OBJECTIVES: To identify variables contributing to discrepant
      gastroesophagopharyngeal acid reflux (GEPR) findings and to critically assess the
      prevalence of GEPR in healthy individuals and patients with reflux laryngitis
      (RL). STUDY DESIGN: Quantitative systematic review. METHODS: Pharyngeal pH
      monitoring studies of healthy individuals and patients with RL were identified
      through a MEDLINE search of publications between 1966 and 2003. Pooled results of
      the measured pharyngeal acid exposure characteristics and the prevalence of GEPR
      events were analyzed. Statistical comparisons were performed using a chi 2 test.
      RESULTS: The study included 181 controls and 184 RL patients. Subjects' age
      ranged from 19 to 85 years. Gastroesophagopharyngeal acid reflux events were
      detected at 1, 2, and 4 cm above upper esophageal sphincter (UES) and 0.5 cm
      below arytenoids, with varying rates. The prevalence of GEPR ranged from 0% to
      83% in controls and 27% to 86% in RL. After excluding the healthy subjects with
      abnormal esophageal acid exposure, prevalence of GEPR decreased from 35% to 17%
      (P<or=.002). Gastroesophagopharyngeal acid reflux in RL was significantly more
      prevalent than in the entire group of controls as well as in controls without
      abnormal esophageal acid exposure (P<or=.001). CONCLUSIONS: The prevalence of
      GEPR in controls and patients with RL varies in the studied 4 areas above the
      UES. The percentage of the subjects with GEPR increased as the probe was located
      more closely to the UES. Differences in demographic characteristics of the
      subjects, interventions used to select subjects, and pharyngeal pH monitoring
      techniques were identified as factors possibly contributing to inconsistent
      pharyngeal pH monitoring findings. The documented differences in methodology of
      existing studies make comparison of the studies difficult.

PMID- 15991090
TI  - Therapeutic effect of lipoprostaglandin E1 on sudden hearing loss.
AB  - PURPOSE: The authors conducted a prospective, comparative clinical trial for the
      purpose of additional effect of lipoprostaglandin E 1 (lipo-PGE 1 ) on sudden
      hearing loss. MATERIALS AND METHODS: With the approval of the institute ethics
      committee, a total of 128 consecutive patients with diagnoses of sudden hearing
      loss were included in the study. The patients in the lipo-PGE 1 group received
      continuous infusion of 10 microL lipo-PGE 1 and 48 mg methylprednisolone for 5
      days, and the patient in the control group were treated with only 48 mg
      methylprednisolone. RESULTS: The total recovery rate after the treatment was
      67.2%. There were 70.5% recovery rate in lipo-PGE 1 group and 60.5% recovery rate
      in control group. However, no significant differences were observed in the
      improvements of pure tone average and subjective symptoms between the lipo-PGE 1
      and control groups. CONCLUSION: The results failed to prove a beneficial effect
      of lipo-PGE 1 in the treatment of sudden hearing loss in spite of its higher cure
      rate.

PMID- 15991091
TI  - Contemporary management of thyroid cancer.
AB  - Thyroid cancer is a relatively common and frequently curable malignant neoplasm,
      accounting for nearly 2% of all new cancers diagnosed annually in the United
      States. The diagnostic and management options have evolved considerably in the
      past decade, and a current understanding of these trends in the standard of care
      have assumed an important consideration in the practices of head and neck
      surgeons and endocrinologists alike. We sought to review the epidemiology and
      pathology of the several types of thyroid cancer and to present our evidence
      based management algorithm. Every effort was made to offer alternative treatment
      strategies and supporting data where available. In addition to reviewing well
      established approaches to diagnosis and management, emphasis is placed on newer
      techniques, including minimally invasive thyroidectomy, molecular detection of
      disease propensity, and the use of recombinant thyrotropin prior to radioiodine
      ablation.

PMID- 15991092
TI  - Aneurysmal bone cyst of the temporal bone associated with reversible hemifacial
      paralysis.
AB  - Aneurysmal bone cyst (ABC) is an uncommon lesion of the temporal bone (TB), with
      only 20 cases reported. Facial paralysis is a rare complication (2 cases);
      however, no cases have been reported with preoperative reversal of paralysis. We
      report a 60-year-old man with a history of remote head trauma, who presented with
      serious otitis media and right hemifacial paralysis, which resolved with
      nonsurgical therapeutic measures. Magnetic resonance imaging and computed
      tomography showed a destructive and expansile lesion of the TB. The lesion was
      surgically removed, and ABC was diagnosed histologically. The patient had an
      uneventful recovery and demonstrated no recurrence at 1 year of follow-up. This
      report presents an unusual presentation of ABC in the TB, with a review of the
      clinical, radiological, pathological, and therapeutic features of this entity.

PMID- 15991093
TI  - Myofibrosarcoma of the nasal bone.
AB  - Myofibrosarcoma is a recently recognized rare tumor that mainly occurs in adults.
      These tumors are composed of a collagenous stroma and pleomorphic stellate to
      spindle-shaped cells that resemble smooth muscle cells with eosinophilic
      cytoplasm and tapered nuclei. We present a case of myofibrosarcoma of the nasal
      bones in a 4-year-old girl who showed rapid enlargement of a painless glabellar
      swelling. Computed tomography and magnetic resonance imaging revealed an
      expanding solid mass with erosion of the surrounding nasal bones. After excision
      and histopathological examination, this tumor was identified as a
      myofibrosarcoma. This is the first report of such a tumor localized to the
      glabellar region. This case report contributes to better awareness of an
      extremely rare type of glabellar lesion in children.

PMID- 15991094
TI  - Flexible fiberoptic bronchoscopy through the laryngeal mask airway in a small,
      premature neonate.
AB  - The laryngeal mask airway (LMA) was introduced as a supraglottic device in
      anesthesia for routine use in the normal adult and pediatric population. Because
      the distal end of properly placed LMA faces the laryngeal inlet, this device can
      be used as a guide to flexible fiberoptic bronchoscopy (FFB) performance. In this
      clinical case, we present a small premature neonate with severe congenital
      biphasic stridor. FFB was performed successfully through the LMA while
      maintaining a patent airway during general anesthesia and permitting spontaneous
      respiration, as well as allowing assisted ventilation when necessary. An
      immediately subglottic intramural mass was revealed and tracheostomy was
      performed.

PMID- 15991095
TI  - Bee stings of children: when to perform endotracheal intubation?
AB  - Hymenoptera stings account for more deaths in United States that any other
      envenomation. Oropharyngeal stings, although rare, may produce life-threatening
      airway obstruction by way of localized swelling. We present 4 cases of bee stings
      in children that necessitated tracheal intubation and mechanical ventilation. Two
      children had breathing difficulties at admission; the other 2 presented with
      minimal symptoms but were preventively intubated and mechanically ventilated.
      Orofacial bee sting victims should be given parenteral treatment with
      epinephrine, steroids, antihistamines, and inhalational bronchodilators even when
      they initially present with minimal symptoms, with general anaphylaxis management
      in large envenomations, as well as immediate endotracheal intubation and
      mechanical ventilation for at least 24 hours in patients with signs of airway
      compromise.

PMID- 15991096
TI  - Autosomal dominant osteopetrosis and maxillomandibular osteomyelitis.
AB  - Osteopetroses represent a heterogeneous group of rare, hereditary bony
      dysplasias. They range from a devastating neurometabolic disease (including
      severe malignant infantile osteopetrosis) to 2 more benign conditions principally
      affecting adults: autosomal dominant osteopetrosis (ADO) type I and type II. The
      present study describes the maxillofacial manifestations associated with the 2
      subgroups of ADO. In this paper, we present the oldest patient described in the
      literature with ADO type I (76 years old). We also document the first ADO type II
      patient described in the literature with synchronic osteomyelitis of the mandible
      and the maxilla.

PMID- 15991097
TI  - Metastatic breast cancer of the oral cavity.
AB  - OBJECTIVE: To present a rare case of breast carcinoma initially presenting as an
      oral cavity mass. STUDY DESIGN: Case report with review of the literature.
      RESULTS: A case is presented of a postmenopausal woman with a remote history of
      treated breast carcinoma who was declared disease-free 2 years before
      presentation. She presented with an enlarging vestibule mass consistent with
      metastatic breast carcinoma. Subsequent investigations revealed widely metastatic
      disease for which the patient was referred for palliative chemotherapy.
      CONCLUSIONS: Metastatic disease to the oral cavity represents only 1% of all oral
      cavity malignancies. A high index of clinical suspicion is necessary when
      evaluating patients with a history of non-head and neck carcinoma.

PMID- 15991098
TI  - The blue rubber bleb nevus syndrome: a case with prominent head and neck
      findings.
AB  - The blue rubber nevus syndrome describes a clinical entity that presents with
      cutaneous and visceral hemangiomas, particularly those found in the
      gastrointestinal tract. These lesions may appear at birth or in early childhood
      and can increase in size and frequency with age. Oral cavity hemangiomas occur in
      59% to 64% of cases. Successful diagnosis requires a high index of suspicion, and
      treatment is symptomatic. This report discusses a unique presentation and a
      review of the literature.

PMID- 15991099
TI  - Mucosa-associated lymphoid tissue lymphoma presented as diffuse swelling of the
      parotid gland.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct subtype of
      lymphoma. Parotid MALT lymphoma is a rare tumor that is hard to diagnose by fine
      needle aspiration cytology. Therefore, partial parotidectomy is often required
      for a pathological diagnosis. We report a case of MALT lymphoma presented as
      unilateral diffuse swelling of the parotid gland, who was diagnosed by partial
      parotidectomy and underwent radiotherapy.

PMID- 15991101
TI  - Shared decision making and nursing informatics research in Norway.

PMID- 15991103
TI  - Patient preferences and cost-utility analysis.
AB  - This column discusses patient preference measures and their application in cost
      utility analysis. A variety of methods of eliciting patient preferences by use of
      generic utility measures are described. Practical issues in the use of utility
      measures are discussed.

PMID- 15991104
TI  - A community model for care of elderly people with diabetes via telemedicine.
AB  - A primary care group diabetes care program using telemedicine was developed and
      its feasibility and acceptability were tested in 22 subjects with Type 2 diabetes
      mellitus using a one-group, pretest-posttest quasi-experimental design.
      Compliance with the program was 100%. Significant reductions in total calorie
      intake as well as body mass index were achieved, with an increase in the
      percentage of subjects achieving better diabetes control as measured by the 2-hr
      hemastix. Improvements in diabetes knowledge and disease-specific and generic
      measures of quality of life were also observed. Most subjects evaluated this mode
      of service delivery favorably in the questionnaire and focus group discussions.
      There is potential for the integration of this mode of service delivery into
      current health services.

PMID- 15991105
TI  - Patient cues that predict nurses' triage decisions for acute coronary syndromes.
AB  - The purpose of this study was to determine the patient cues that emergency
      department (ED) nurses use to triage male and female patients with complaints
      suggestive of acute coronary syndromes (ACSs) and to determine if cues used by ED
      nurses to make clinical inferences varied by patient sex or nurses' demographic
      characteristics. Using clinical vignette questionnaires with different patient
      characteristics, ED nurses' triage decisions were evaluated to determine the
      patient cues used to predict ACS. Men and women were equally likely to be given
      an ACS triage decision and this was not affected by nurses' demographic
      characteristics. However, nurses used different cues to triage men and women with
      complaints suggestive of ACS, although by receiver operating characteristic
      curves, the differences between sexes were small. In addition, female vignette
      patients were more likely than male vignette patients to be assigned a suspected
      cause of cholecystitis for their presentation in a small subset of 13 (11:2; odds
      ratio, 1.653; 95% confidence interval, 1.115-24.47; p=.036). This study provides
      insight into the complex phenomenon of triage decision making and warrants
      further exploration.

PMID- 15991106
TI  - Patients' choices for the self-treatment of pain.
AB  - Pain is a common problem that affects the functional status and quality of life
      of people in all communities. This study explored the occurrence of pain and the
      pain self-treatment modalities used by 723 community residents. Mean worst pain
      scores were moderate to severe and interfered with all activities at a low-to
      moderate level. Participants reported taking nonopioid analgesics (75%), opioid
      analgesics (15%), adjuvant analgesics (11.6%), and herbal products and
      supplements (29%); 68% used nonpharmacological modalities. Current regimens were
      reported to relieve only 45% of pain. Twenty-eight percent of participants
      reported that they had not informed their primary care practitioner of their self
      treatment choices. Knowledge of self-treatment choices is imperative in planning
      treatment regimens for pain or other health problems to prevent potential
      interactions or side effects.

PMID- 15991107
TI  - Identifying family care process themes in caring for their hospitalized elders.
AB  - Little is known about strategies used by family caregivers for their hospitalized
      elderly relatives. A total of 16 participants were recruited in this qualitative
      study from two hospitals in the northwest of the United States. Altogether, 25
      interviews and 3 participant observations were conducted with hospitalized
      elders, family caregivers, and nurses. Qualitative analysis based on Lofland and
      Lofland's approach resulted in the identification of five family care process
      themes: (a) carrying on, (b) modifying, (c) starting new, (d) sharing, and (e)
      arranging care for. Understanding how family caregivers provide care can help
      nurses to work effectively with family caregivers to improve the outcomes of
      hospitalized elders.

PMID- 15991108
TI  - Clinical coordination of research.
AB  - A feeding study conducted at a tertiary care center's neonatal intensive care
      unit tested a predictive model of bottle-feeding readiness and feeding outcomes.
      The study examined how bottle-feeding experience influences both bottle-feeding
      readiness and outcomes. The clinical coordinator played an integral role in the
      success of the research by coordinating the education of nurses, data collectors,
      and families; communicating with various interest groups; managing recruitment,
      enrollment, and participant tracking; and overseeing data collection.

PMID- 15991109
TI  - "Eating-together" mealtimes with African-American fathers and their toddlers.
AB  - The prevalence of obesity is increasing at an alarming rate in African-American
      children. Fathers influence mealtime behaviors but are often overlooked in
      nutrition education. A sample of six African-American fathers of toddlers
      participated in a focus group to describe mealtime behaviors with their toddlers.
      The focus group was audiotaped and transcribed verbatim. Five thematic categories
      were identified: mealtime rituals and routines, division of responsibility,
      family constellation, nutritional knowledge, and tension during mealtimes.
      Fathers expressed frustration with the toddler's "picky-eater" developmental
      stage. Fathers need to be included in nutrition education that promotes healthy
      mealtime habits with their toddlers.

PMID- 15991110
TI  - Driving strategies used by older adults with macular degeneration: assessing the
      risks.
AB  - Older adults with macular degeneration use multiple driving strategies. A
      secondary analysis focused on driving strategies was conducted on data from two
      studies that had explored the experience of visual impairment in older adults
      diagnosed with macular degeneration. Findings revealed 24 driving strategies.
      Twelve categories emerged, reflecting two themes: (1) strategies used while
      performing the task of driving and (2) strategies used to continue driving. By
      understanding these strategies, nurses can assess the conditions under which
      these older adults drive and the risks taken. Findings guide nurses to counsel
      and educate older adults regarding driving.

PMID- 15991111
TI  - Evaluating risk factors for violence at the inpatient unit level: combining young
      adult patients and those with mental retardation.
AB  - The current study demonstrates the use of patient case mix to evaluate the
      probability of aggression occurring on an inpatient psychiatric unit. The impact
      of combining young adult psychiatric patients with patients classified with
      mental retardation on the overall negative events and injuries on an inpatient
      psychiatric unit was evaluated. Results suggest when the combined number of young
      adults and patients classified with mental retardation exceeds 10 the unit is at
      high risk for aggressive behavior occurring. Recommendations for evaluating
      violence at a unit level using case mix are provided.

PMID- 15991112
TI  - Predicting pressure ulcer risk with the modified Braden, Braden, and Norton
      scales in acute care hospitals in Mainland China.
AB  - The aim of this study was to develop a modified Braden scale, to evaluate its
      predictive validity, and to identify a more valid pressure ulcer risk calculator
      for application in acute care hospitals in Mainland China among the modified
      Braden, Braden, and Norton scales. The initial modified Braden scale, with the
      addition of skin type and body build for height, was proposed in this study. Four
      hundred twenty-nine subjects who were admitted to two acute care hospitals in
      Mainland China within 24 hr and free of pressure ulcers upon admission were
      assessed with the initial modified Braden, Braden, and Norton scales by three
      nurse assessors. This was followed by a daily skin assessment to note any
      pressure ulcer by a nurse assessor. Nine subjects had pressure ulcers detected at
      Stages I (89%) and II (11%) after an average stay of 11 days. The descriptive
      analysis of each subscale scoring item in the initial modified Braden scale
      indicated that skin type and body build for height were the most distinct
      predictive factors whereas nutrition was the least distinct factor for predicting
      pressure ulcer development. Based on these findings, the modified Braden scale
      was further developed with the addition of skin type and body build for height
      and by exclusion of nutrition. The predictive validity test reported that the
      modified Braden scale demonstrated a better balance of sensitivity (89%) and
      specificity (75%) at a cutoff score of 16, with a higher positive predictive
      value (7%), than the Braden and Norton scales. This finding revealed that for
      this sample, the modified Braden scale is more effective in pressure ulcer risk
      prediction than the other two scales. Because the modified Braden scale is not
      100% sensitive and specific, to increase clinical efficacy in the prevention of
      pressure ulcer, it is recommended that it be adopted combined with nursing
      judgment to predict pressure ulcer development in acute care settings in Mainland
      China.

PMID- 15991117
TI  - Making your next unicompartmental knee arthroplasty last: three keys to success.
AB  - Alignment, ligament balance, and implant fixation are essential in
      unicompartmental knee arthroplasty. Adequate exposure allows assessment of the
      opposite compartment, trimming of medial femoral and tibial osteophytes, and a
      thorough notchplasty. Intramedullary instruments provide accurate and
      reproducible alignment of the implants in extension, and the anteroposterior axis
      offers the best landmark for varus-valgus alignment in flexion and also centers
      the femoral component on the surface of the tibial component. Complete osteophyte
      excision frees the collateral and cruciate ligaments and minimizes ligament
      balancing. The implants should allow 1 to 3 mm of laxity in flexion and
      extension, and if more laxity is required, reresection should be done posteriorly
      or distally. Fixation depends on excellent bone stock along with precise
      alignment, and avoiding tibial overresection ensures adequate support of the
      implant.

PMID- 15991118
TI  - Patellofemoral arthroplasty: the third compartment.
AB  - Isolated arthritis on the patellofemoral articulation has received minimal
      attention in the past. It is now recognized to be relatively common, especially
      in women. Treatment alternatives such as patellectomy, unloading osteotomies,
      debridement, and cartilage transplant have not offered long-term sustainable
      benefits. Therefore, there is a need for a reliable patellofemoral arthroplasty.
      The current indications for surgery include middle-aged patients with isolated
      patellofemoral arthritis without severe maltracking, inflammatory arthritis,
      crystalline arthropathy, femorotibial arthritis, or high demands. Reports show
      60% to 80% good-to-excellent results in the short term and midterm. The main
      problems with patellofemoral arthroplasty have been patellar instability and
      patellar edge loading on the condylar cartilage in flexion. Newer designs are
      addressing both issues and are leading to improved results.

PMID- 15991119
TI  - Choosing your implant: cemented, tricompartmental, and posterior stabilized.
AB  - Cemented, posterior-stabilized, tricompartmental implants have yielded excellent
      relief of pain and are applicable to almost all clinical situations. The
      complications and revision rates after routine patellar resurfacing are less than
      those seen without such resurfacing. Cine fluoroscopic studies have shown that
      they restore a more normal kinematic pattern than do posterior cruciate ligament
      retaining implants and have a low rate of radiographic and/or clinical loosening
      when followed up through 15 years after surgery. Latest posterior stabilized
      designs can allow a higher degree of flexion than seen in any other combination
      of implant designs. It is for all these reasons that the author feels that this
      method of performing a knee arthroplasty is the gold standard.

PMID- 15991120
TI  - Choosing your implant: cementless, patella sparing, and posterior cruciate
      ligament retaining.
AB  - Clinical results of total knee arthroplasty with osteointegration techniques for
      fixation of the femoral and tibial components in a series of 192 patients (255
      knees) followed up for 15 to 18 years are comparable with the best series
      reported with cemented fixation. Although functional scores declined as the
      patients aged, pain scores did not worsen, and the mechanical failure rate
      remained low through follow-up. Preservation of the posterior cruciate ligament
      offered knee stability, especially in knees that required ligament balancing.
      Results with unresurfaced patellas in total knee arthroplasty are superior to
      resurfaced patellas in qualities related to quadriceps function such as stair
      climbing, likely because of femoral component design. Femoral implants with a
      shallow patellar groove and wide intercondylar notch produce the highest stresses
      on the unresurfaced patella. Those with deeper patellar grooves and supporting
      lateral flange surfaces have low contact stress similar to that of the normal
      patellofemoral joint.

PMID- 15991121
TI  - Deep vein thrombosis prophylaxis: better living through chemistry--in the
      affirmative.
AB  - Venous thromboembolism is a recognized complication of total hip arthroplasty,
      knee arthroplasty, and hip fracture surgery. Various pharmacological agents have
      been introduced in orthopedic surgery in an attempt to reduce the mortality as
      well as the short-term and long-term morbidity associated with the development of
      deep vein thrombosis and pulmonary embolism. Clinical trials demonstrate the
      increasing thromboprophylactic efficacy of newer generations of drugs. The most
      current guidelines of the American College of Chest Physicians regarding
      thromboprophylaxis after total hip arthroplasty, total knee arthroplasty, and hip
      fracture surgery give the highest recommendations in support of the use of low
      molecular-weight heparin, warfarin, or fondaparinux. Their highest recommendation
      is also given against the use of aspirin due to its lack of demonstrated
      efficacy.

PMID- 15991122
TI  - Deep venous thrombosis prophylaxis: better living through chemistry--in
      opposition.
AB  - The best prophylactic regimens for thromboembolic disease continue to be debated
      despite years of investigation. The surgeon must balance the clinical risks and
      benefits. A decision depends on accurate data and our ability to balance the
      risks of fatal pulmonary embolism (PE) to the risk of bleeding. The current risk
      for fatal PE is 0.1% with most current prophylactic regimes. The risk of
      perioperative bleeding increases 1.8% to 5.2% with low molecular weight heparins
      or warfarin and generally is dose dependent. Most of the current prophylactic
      recommendations are based on the presence or absence of deep venous thrombosis
      (DVT). However, the correlation between the presence of a DVT and the risk of PE
      is low and inconsistent. Therefore, DVT may not be an accurate surrogate marker
      for the patient at risk after total joint surgery. Our experience with 2800
      consecutive total knee arthroplasty patients, using aspirin as our principle
      agent, shows a fatal PE risk of 0.1% and a low risk of bleeding. Therefore, our
      current recommendation is aspirin.

PMID- 15991123
TI  - A comedy of errors: the bad knee.
AB  - A review of 241 consecutive total knee revisions has been carried out. Other than
      loosening, wear, and stiffness, at present, a commoner reason is an
      unsatisfactory result due to minor errors of tibial and femoral placement.
      Currently, about 16% of femoral components required derotation during revision.

PMID- 15991124
TI  - The stiff total knee arthroplasty: causality and solution.
AB  - A stiff total knee arthroplasty is a disabling condition, which can be caused by
      technical errors, patient factors, and postoperative complications. The results
      of treatment are dependent on the cause of stiffness. The best treatment is
      prevention by providing preoperative patient education, aggressive postoperative
      rehabilitation, and avoidance of technical errors. Early manipulation may improve
      motion with a well-aligned component. Open arthrolysis and revision arthroplasty
      are indicated for chronic stiffness with component malposition or failure,
      incorrect component sizing, joint line displacement, or inadequate bone
      resection. When performing a revision arthroplasty, it is important to know the
      reason for failure and loss of motion because failure to identify the cause of
      stiffness may result in recurrence of the problem.

PMID- 15991125
TI  - Periprosthetic fractures after total knee arthroplasty.
AB  - Fractures around total knee arthroplasties are challenging clinical problems and
      include the following: stress fractures of the pelvis and femoral neck,
      supracondylar femur fractures, fractures of the proximal tibial metaphysis and
      diaphysis, and patellar fractures. Treatment focuses on restoration of the
      patient's prefracture functional status. The etiology of supracondylar femur
      fractures is multifactorial and treatment includes immobilization, retrograde
      intramedullary nailing, open reduction and internal fixation, and revision
      arthroplasty. The "Less Invasive Stabilization System" plate has recently been
      added to the list of viable fixation options. Tibial metaphyseal and diaphyseal
      fractures are less common and usually treated with revision arthroplasty. In the
      absence of maltracking or component loosening, vertical patellar fractures often
      respond to immobilization. Disruption of the extensor mechanism may require
      cerclage wiring or even extensor mechanism allografting if chronic. Conventional
      tension band wiring usually fails. Patellar fractures are controversial and
      problematic.

PMID- 15991126
TI  - The infected total knee: management options.
AB  - The management of infection after total knee arthroplasty depends on the
      chronicity of the infection, host factors, and sensitivity of the infecting
      bacteria. Two-stage salvage consisting of removal of implants and cement,
      placement of an antibiotic spacer, and appropriate intravenous antibiotic therapy
      followed by reimplantation with an antibiotic-impregnated cement appears to be
      the predominant approach to managing this complication. The use of articulated
      spacers consisting of the sterilized femoral and polyethylene components with
      antibiotic cement allows maintenance of motion and bone stock. This report
      details the author's experience with 44 infected knee arthroplasties.

PMID- 15991127
TI  - Preoperative planning for revision total knee arthroplasty:avoiding chaos.
AB  - Use of preoperative planning is important in avoiding an unstable revision total
      knee arthroplasty. Physical examination should determine the status of the
      collateral ligaments so that implants with appropriate constraint are made
      available. Radiographic examination should determine if bone loss is present and
      whether primary or revision implants will be needed. Preoperative determination
      of the joint line position will simplify the surgery and facilitate
      flexion/extension space balancing. Three hundred sixty-five revision total knee
      arthroplasty surgeries were performed from 1987 to 2003. Of those, 82% were
      performed with unconstrained implants. Ten percent of the knees required
      varus/valgus constraint and 8% knees used rotating hinge components. Use of
      preoperative planning techniques resulted in postoperative stability in 99% of
      the revision total knee arthroplasties performed.

PMID- 15991128
TI  - The role of implant constraint in revision total knee arthroplasty: not too
      little, not too much.
AB  - The goal of revision total knee arthroplasty is to restore the anatomical
      alignment of the knee and to provide a stable joint. Joint stability is obtained
      by balancing the various knee ligaments remaining at the time of revision surgery
      and by using an implant with added stability if necessary. Understanding the
      limits of the various designs available (cruciate retaining, cruciate
      substituting, valgus-varus constraining, and linked) should help the surgeon
      construct a stable and durable construct.

PMID- 15991129
TI  - What would you do? Case challenges in knee surgery.
AB  - These knee arthroplasty cases were presented to a panel of surgeon and they
      represent classic clinical problems: (1) indications for unicompartmental
      arthroplasty; (2) total knee arthroplasty after a high tibial osteotomy
      complicated by infection and extensor mechanism rupture; (3) neuropathic
      arthropathy; (4) posttraumatic osteoarthritis with extraarticular deformity; (5)
      degenerative arthritis in the young patient; (6) osteoarthritis with a valgus
      deformity, fixed flexion contracture, degenerative scoliosis, and leg length
      discrepancy.

PMID- 15991130
TI  - Blood management: issues and options.
AB  - Blood management in the perioperative period of the total joint arthroplasty
      procedure has evolved over the last 3 decades. Strategies have changed and are
      changing based on a better understanding of blood loss and blood replacement
      options in this patient population. Patient-specific options based on
      preoperative hemoglobin levels and patient comorbidities as well as anticipated
      blood loss have been developed and studied. Patient-specific blood management
      programs have provided cost-efficient care with low morbidity.

PMID- 15991131
TI  - Highly cross-linked polyethylene: the debate is over--in the affirmative.
AB  - Highly radiation-cross-linked, subsequently melted ultrahigh molecular weight
      polyethylene (XLP) has rapidly gained wide acceptance in total joint arthroplasty
      as a means to markedly reduce wear and the associated periprosthetic osteolysis.
      Several laboratory studies have shown negligible wear of XLP in both hip and knee
      for durations simulating 20 years of in vivo service. Three clinical studies
      involving 3 different demographic groups and 2 different measurement techniques
      have found that the femoral head penetration after bedding-in is less than 10
      mm/y. Retrieval acetabular and tibial specimens up to 3 years after insertion
      have confirmed the absence of wear and oxidation. With in vivo experience now
      over 5 years, it appears that XLP is the material of choice in total joint
      arthroplasty.

PMID- 15991132
TI  - Highly cross-linked polyethylene: the debate is over--in opposition.
AB  - Highly cross-linked polyethylene compared to conventional ultra high molecular
      weight polyethylene (UHMWPE) results in significantly decreased wear in hip
      simulators and early prospective randomized clinical studies. However, the
      contact stresses in a total knee bearing surface are much higher than in a total
      hip. As a result, fatigue wear mechanisms occur more typically in total knee
      compared with total hip arthroplasty. Cross-linking reduces the mechanical
      properties of UHMWPE including fatigue crack propagation resistance, which may
      limit its role in total knee arthroplasty. Although the in vitro and in vivo
      studies provide compelling evidence that highly cross-linked polyethylene may
      improve the longevity of total hip arthroplasty, it does not appear to offer
      similar benefits for total knee arthroplasty.

PMID- 15991133
TI  - The tapered press fit total hip arthroplasty: a European alternative.
AB  - The tapered rectangular press fit femoral component design of Karl Zweymuller
      remains highly successful since its inception in 1979. The longitudinal taper and
      rectangular cross-section provide unequaled primary stability, which promotes
      consistent secondary osseointegration to the grit-blasted titanium surface, even
      in osteoporotic bone. The "fit without fill" concept provides for bone
      conservation and preservation of the intraosseous blood supply by compaction,
      rather than removal, of the metaphyseal cancellous bone. The surgical technique
      is simple and forgiving, allowing for infinite adjustability in stem height and
      anteversion. Numerous long-term studies report excellent clinical results with a
      negligible incidence of loosening, thigh pain, osteolysis, or significant stress
      shielding and survivorships approaching 100% at 10 years.

PMID- 15991134
TI  - Metal-on-metal resurfacing arthroplasty: no way under the sun!--in the
      affirmative.
AB  - I have been charged in this debate format to refute the idea suggested in the
      title. To do this, I will address 2 questions: (1) What problem does it solve?
      and (2) What risk does it pose? The answers to these questions will support my
      conclusion that metal-on-metal resurfacing arthroplasty is the wrong operation to
      be making a reappearance at this time.

PMID- 15991135
TI  - Metal-on-metal resurfacing arthroplasty: no way under the sun!--in opposition.
AB  - The functional demands and the longevity of hip arthroplasty patients are
      increasing. High volumetric wear and osteolysis limit the durability of metal
      ultra high molecular weight polyethylene resurfacing. Cemented femoral
      hemiresurfacing components (no acetabular component) do not develop osteolysis
      and rarely loosen. Consistent long-term fixation has been demonstrated with
      hemispherical cementless acetabular components. Metal-metal bearings have
      demonstrated low wear and rare osteolysis over 3 decades of use. These facts form
      foundation for total hip resurfacing with metal-metal bearings.

PMID- 15991136
TI  - Cemented femoral revision: lest we forget.
AB  - Cemented femoral revisions can provide durable fixation when used for specific
      indications. These indications include elderly patients with minimal bone loss or
      large femoral canals and the cement-within-cement technique where a new femoral
      component is cemented into an intact cement mantle.

PMID- 15991137
TI  - The surgical management of femoral osteolysis.
AB  - Fifteen patients underwent reoperation for failed total hip arthroplasty. At
      surgery, patients who had proximal femoral osteolysis with osseointegrated
      femoral components were managed with lesional treatment that included debridement
      and bone grafting. The femoral components included 7 extensively coated stems, 5
      proximally coated stems, and 3 modular femoral components. At a minimum 5-year
      follow-up evaluation, all 15 femoral components remained radiographically stable.
      Graft material in contained defects appeared to consolidate radiographically. For
      selected patients, debridement and grafting of femoral osteolytic defects provide
      satisfactory intermediate term outcomes.

PMID- 15991138
TI  - The treatment of pelvic discontinuity during acetabular revision.
AB  - Pelvic discontinuity is frequently encountered during acetabular revision in
      patients with severe acetabular bone loss. Prompt recognition of the
      discontinuity and appropriate intraoperative management are essential for a
      successful clinical outcome. The treatment of the discontinuity is dependent upon
      the remaining host bone, the potential for healing of the discontinuity, and the
      potential for biologic ingrowth of acetabular components. If healing potential of
      the discontinuity exists, the discontinuity should be treated in compression with
      a posterior column plate and structural allograft or with the use of trabecular
      metal acting as an internal plate. If healing potential for the discontinuity
      does not exist, the discontinuity can be bridged and treated in distraction with
      either an acetabular transplant supported with a cage or with the use of a custom
      Triflange implant. However, the poor clinical results observed with either of
      these treatment modalities for a type IIIB defect with an associated pelvic
      discontinuity have prompted the senior author to explore the use of a trabecular
      metal acetabular component with 1 or 2 augments in the majority of his current
      type IIIB cases. The long-term clinical results of this treatment remain unknown.

PMID- 15991139
TI  - Management of acetabular bone stock deficiency.
AB  - Acetabular bone stock deficiency in primary and revision total hip arthroplasties
      can usually be effectively managed by combining the use of appropriately designed
      implants and structural or nonstructural bone grafts or bone graft substitutes.
      An appreciation of the deformity before surgery will allow for proper planning
      and execution of a plan at the time of surgery. The presence of segmental defects
      or pelvic instability is particularly important to assess preoperatively.
      Adherence to basic principles of bone grafting and implant fixation allows
      surgeons to reliably manage these potentially difficult problems.

PMID- 15991140
TI  - Rebuilding the skeleton: the intraoperative use of trabecular metal in revision
      total hip arthroplasty.
AB  - Cages provide a scaffold for restoration of bone stock in revision arthroplasty
      of the acetabulum. A major problem with cages is failure at 5 to 10 years due to
      loss of fixation. The present generation of cages are not made of a material that
      provides biologic fixation. Trabecular metal cups provide excellent biologic
      fixation and a favorable environment for bone graft remodeling. For large bone
      defects where there is not optimal contact with host bone at the correct anatomic
      level, a trabecular cup is placed against bone graft, fixed with screws, and
      protected by a cage into which the polyethylene cup is cemented. The initial
      stability is via the cage, but when graft remodeling takes place, the stress will
      be taken by the trabecular metal relieving the stress on the cage.

PMID- 15991141
TI  - Bone graft extenders, substitutes, and osteogenic proteins.
AB  - A number of products that serve as a bone graft substitutes or graft extenders
      are currently available. Osteoconductive products provide a porous 3-dimensional
      structure that encourages bone ingrowth. These materials are readily resorbed by
      osteoclasts leading to turnover into host bone at variable rates. Some calcium
      phosphate products act as cements in that they are liquid upon preparation and
      harden at body temperature. These cements resist compressive forces but are not
      effective in resisting shear or torsion. Calcium sulfate resorbs more quickly
      than calcium phosphate and has the potential to serve as a carrier for drugs or
      growth factors. Preclinical studies have shown that the osteoinductive capacity
      of autograft and allograft bone can be improved substantially with the addition
      of osteogenic proteins. Although no detailed clinical studies have been reported
      to date, anecdotal reports of their use with and without bone graft indicate
      results consistent with those obtained in preclinical studies.

PMID- 15991142
TI  - What would you do? Case challenges in hip surgery.
AB  - Evaluation and management of 4 challenging hip case scenarios were discussed in
      an interactive session with a moderator and 5 experts in hip reconstruction. Case
      based discussion included total hip arthroplasty for posttraumatic arthritis
      after acetabular fracture, total hip arthroplasty after failed intertrochanteric
      hip fracture, total hip arthroplasty for hip dysplasia, and total hip
      arthroplasty in the case of proximal femoral deformity.

PMID- 15991143
TI  - Last words.

PMID- 15991144
TI  - The psychiatric nurse practitioner 1993-2003: a decade that unsettled a
      specialty.
AB  - Between 1993 and 2003, a debate raged in psychiatric mental health (PMH) nursing.
      It was a decade of discourse about the role and titling of PMH advanced practice
      nurses. The PMH role evolution that occurred throughout this decade was driven by
      several forces, not all of which were in the control of PMH nursing. This article
      traces the multiple dynamics that prompted the evolution of the PMH nurse
      practitioner role, foremost the ascendancy of primary care and the influence of
      managed care. It also analyzes the conflict created by the American Nurses
      Credentialing Center PMH Nurse Practitioner examination that became a lightning
      rod for the disruption occurring in the traditional PMH role. Although the
      controversy surrounding PMH advanced practice nurse titling is beginning to
      clear, with the clarity comes a new set of problems for the development of the
      PMH workforce.

PMID- 15991145
TI  - Family history as a tool for psychiatric nurses.
AB  - In the current age of genomic health care, family history is an essential tool
      for health assessment, especially for those with chronic mental illness. Three
      methods of family history assessment (genograms, ecomaps, and pedigree analysis)
      are described and illustrated. Examples from the family history literature
      demonstrate each method's usefulness. These approaches improve both consumers'
      and psychiatric nurses' abilities to comprehend overall health status as well as
      risks at the individual, family, and community levels.

PMID- 15991146
TI  - Barriers to community integration for participants in community-based psychiatric
      rehabilitation.
AB  - This pilot study examined barriers to community integration for adults with
      serious mental illness (SMI) enrolled in a community-based psychiatric
      rehabilitation program. Program staff administered a self-report scale to 135
      adults (mean age = 43.3 years, 53% men, 65.1% White). Staff completed the same
      measure. Individuals with mental illness and staff differed significantly in
      their reports of the type, number, F (1, 73) = 29.25, P < .0001, and severity (F
      (1, 176) = 43.53, P < .0001) of barriers to community integration. Clinicians
      should assist adults with SMI to identify relevant barriers, and participate in
      treatment planning and outcome evaluation.

PMID- 15991147
TI  - Depressive symptoms and learned resourcefulness among Taiwanese female
      adolescents.
AB  - Depression in adolescents is a widespread problem and has negative consequences
      on mental health, including suicidal tendencies. Worldwide, this condition is
      twice as prevalent in females as in males. To identify factors that may affect
      the development of depression in female adolescents in Taiwan, a cross-sectional,
      correlational design was used to examine the relationships among stressors,
      learned resourcefulness, and depressive symptoms. Four hundred four Taiwanese
      female adolescents participated in the study. Descriptive statistics and
      hierarchical multiple regression were used to analyze data. The study findings
      suggested that low household income, dissatisfaction with grades, perceived poor
      health state, and poor peer relationships were significant stressors that
      contribute to the development of depressive symptoms. Adolescents with greater
      learned resourcefulness had fewer depressive symptoms. In addition, learned
      resourcefulness mediated the effects of perceived health and peer relationships
      on depressive symptoms. Health-care providers can use this knowledge to teach
      adolescents coping strategies such as use of learned resourcefulness to prevent
      depression and its negative consequences.

PMID- 15991148
TI  - Psychiatric nurses' anxiety and cognition in managing psychiatric patients'
      aggression.
AB  - This study explored the anxiety, attitudes, and cognition of the need for
      aggression management among Taiwanese psychiatric nurses caring for psychiatric
      patients. Data were collected with self-report questionnaires from 180
      psychiatric nurses in the acute wards of three large psychiatric centers in
      Taiwan. Results showed increased threat of cognitive appraisal of aggression,
      increased trait anxiety, and decreased positive attitudes toward aggression
      predicted higher levels of state anxiety. There were significantly higher levels
      of state anxiety among psychiatric nurses when patients exhibited verbal and
      physical aggression rather than just physical aggression. An important outcome of
      this study is the added understanding of cognitive appraisal, trait anxiety, and
      attitudes, that influence the anxiety of psychiatric nurses.

PMID- 15991149
TI  - Nursing students' personal experiences involving alcohol problems.
AB  - This article discusses the views and beliefs of nursing students toward people
      who abuse alcohol. An original study published in a separate article [Archives of
      Psychiatric Nursing , (2003); (4) 17 : 156-164.] examined this relationship with
      both a quantitative and a qualitative design. Three open-ended questions allowed
      for further qualitative exploration about relationships with others who have
      alcohol problems and beliefs about recovery. The chronic nature of alcoholism was
      clearly identified by students who described it as a lifelong process. Most
      students (79%) expressed belief that recovery was possible whether they had
      personal experience with people who have alcohol problems or not. The level of
      optimism was surprisingly high in this sample of nursing students, especially
      because many had had a personal experience with someone who abused alcohol.
      Students come to the educational setting with a clear and accurate view of the
      lifelong commitment that may be needed to recover from alcohol addiction, but
      they also come with an overly optimistic view of recovery. How this optimism
      impacts future care is unknown. If nursing students hold an unrealistically
      positive view of recovery, they may be ill prepared to handle the disappointments
      associated with treatment such as relapse, interpersonal conflict, health
      deterioration, or other related sequelae.

PMID- 15991150
TI  - Cardiovascular effects of ephedra alkaloids: a comprehensive review.
AB  - The Ephedra alkaloids have received much press lately secondary to reported
      adverse events in those using whole extracts as "dietary supplements" for weight
      loss or athletic performance enhancement. These reports are troubling given the
      increasing use of these supplements by the general public. We reviewed the
      available literature as well as online material on these compounds, including
      information on their pharmacology, regulation, effects on weight loss and
      athletic performance, and adverse events. Extracts of Ephedra shrubs contain
      highly active alpha- and beta-adrenergic agonists that have profound effects on
      the heart and vasculature. Evidence for their effectiveness is limited. Adverse
      cardiovascular and cerebrovascular effects, including stroke, myocardial
      infarction, and sudden death, temporally related to their use are well described.
      The recent Food and Drug Administration ban on these compounds is not broad
      enough. Ephedra supplements contain a highly bioactive class of compounds that
      pose a significant risk to the public under the current regulatory framework.
      More stringent oversight by regulatory authorities is required to minimize the
      incidence of adverse events.

PMID- 15991151
TI  - Brucella endocarditis: the importance of surgical timing after medical treatment
      (five cases).
AB  - INTRODUCTION: Brucella endocarditis is a disease that is hard to treat medically
      and has a high mortality. Immediate surgery after medical treatment is very
      important because delaying surgery may lead to that are difficult to repair.
      METHODS: Five patients who were admitted to our institution with a diagnosis of
      Brucella endocarditis were medically treated with doxycycline (200 mg/d),
      rifampin (600 mg/d), and ceftriaxone (2 g/d). Preoperative mean medical treatment
      time was 5.2 weeks (range, 4-6 weeks). The patients were taken for operation when
      their general status improved. We report in this study the results of these
      patients. RESULTS: Three patients had aortic valve replacement whereas 2 had both
      aortic and mitral valve replacements. No mortality or morbidity was encountered
      in the patients. Mean postoperative hospitalization time was 15 days (range, 12
      19 days). The patients were discharged with doxycycline (200 mg/d) and rifampin
      (600 mg/d) but without antipyretic medication. Postoperative antibiotherapy was
      continued up to a mean of 3.6 months (range, 2-6 months). Mean postoperative
      follow-up time was 15.8 months. None of the patients needed hospitalization in
      their follow-up time. CONCLUSION: Adequate preoperative antibiotherapy, immediate
      surgery, and continuation of postoperative antibiotherapy according to clinical
      progress seem to be a convenient treatment strategy for Brucella endocarditis.

PMID- 15991152
TI  - Chlamydia pneumoniae and atherosclerosis: from Koch postulates to clinical
      trials.
AB  - Atherosclerosis is increasingly viewed as an inflammatory process. A number of
      infectious agents have been implicated in the pathogenesis of coronary artery
      disease. Chlamydia pneumoniae has been the most popular and well-studied of these
      pathogens. It is difficult to prove a causal relationship which requires the
      fulfillment of Koch's postulates, first developed in the late 1800s, to establish
      an infectious agent as the cause of a disease process. This paper reviews the
      evidence for and against Chlamydia pneumoniae infection as a contributing factor
      to atherosclerosis disease. It examines seroepidemiologic and histopathologic
      studies as well as animal models using Koch's postulates and then provides an
      analysis of current clinical trial data.

PMID- 15991153
TI  - Predicting perioperative cardiac risk.
AB  - Cardiovascular complications are the major cause of perioperative morbidity and
      mortality of patients undergoing major vascular surgery. This is related to the
      frequent presence of an underlying coronary artery disease. This paper reviews
      the pathology of perioperative cardiac complications and cardiac risk assessment
      and risk reduction strategies. Guidelines of the American College of Cardiology
      and American Heart Association for the evaluation of cardiac risk for noncardiac
      surgery may provide the necessary framework for the assessment and management of
      patients undergoing major vascular surgery. Based on the American College of
      Cardiology and American Heart Association guidelines and data from contemporary
      studies, patients without risk factors are considered to be at low risk and do
      not require additional evaluations for coronary artery disease. Patients with 1
      or 2 cardiac risk factors represent an intermediate-risk group for perioperative
      cardiac complications. If beta-blockers are prescribed, the probability of
      cardiac complications is low and there is no need for further noninvasive
      testing. Patients with 3 or more risk factors are at high risk for cardiac
      complications and the use of noninvasive testing may help further refine cardiac
      risk based on the presence and absence of test-induced myocardial ischemia. beta
      Blockers should be prescribed to all patients, and coronary revascularization
      should be reserved for high-risk patients who have a clearly defined need for
      revascularization independent of the need for major vascular surgery.

PMID- 15991154
TI  - Postmortem studies of the intertruncal plexus and cardiac conduction system from
      patients with Chagas disease who died suddenly.
AB  - Throughout the cardiac conduction system of each heart there were numerous
      destructive lesions including focal inflammatory infiltration with lymphocytes
      and in neighboring regions extensive focal fibrotic degeneration. These lesions
      involved myocytes, nerves and blood vessels. They were adequate explanation for
      the familiar disturbances in cardiac rhythm and conduction typical of Chagasic
      cardiomyopathy. In one heart there was a left ventricular apical aneurysm, which
      is often considered typical of Chagasic cardiomyopathy. To our surprise,
      virtually every myocyte in the region of the aneurysm was undergoing extensive
      dehiscence, thus severing all intercellular junctions of the involved myocytes.
      Therefore, we suggest that the left ventricular apical aneurysms represent a form
      of disuse atrophy produced by the sympathetic denervation caused by
      neuropathology in the intertruncal plexus of each heart. Sympathetic innervation
      of virtually the entire left ventricle is derived from nerves supplied through
      ganglia in the intertruncal plexus. The random nature of the neuropathology in
      the intertruncal plexus is the probable explanation of why some Chagasic hearts
      exhibit generalized Chagasic cardiomyopathy, while others have a more restricted
      denervation ending in left ventricular apical aneurysms. Perhaps the most
      intriguing finding in our study was the abundance of flagellated trypanosoma
      cruzi within the intertruncal plexus of each heart. The trypanosomes were often
      in clusters, sometimes encysted by a thin fibrous membrane, but more often in
      loose aggregates without a surrounding membrane. Some trypanosomes were seen
      boring into intertruncal nerves while others formed dense clusters of
      trypanosomes attached to the outer surface of an intertruncal vein. We believe
      that these observations have seldom, if ever, been described before, and they
      represent interesting opportunities in future diagnosis and treatment of cardiac
      disease caused by trypanosoma cruzi.

PMID- 15991155
TI  - Matrix, cytoskeleton, or myofilaments: which one to blame for diastolic left
      ventricular dysfunction?
AB  - During cardiac filling, the relative contribution of distension of interstitial
      collagen, of distension of cytoskeletal proteins, and of low-grade diastolic
      cross-bridge cycling in the generation of diastolic left ventricular (LV)
      pressure remains unclear. In failing myocardium, interstitial collagen deposition
      and cross-linking are augmented. This increase in collagen deposition is
      accompanied by expression of a stiffer isoform of titin in the cardiomyocytes.
      Higher diastolic stiffness of failing myocardium is therefore not necessarily
      related to increased interstitial collagen content. Moreover, phosporylation of
      titin by protein kinase A and G, and inhibition of titin-actin interaction by
      cytosolic calcium allow for dynamic modulation of its diastolic tension
      generation and could account for acute shifts of myocardial distensibility. Acute
      shifts of myocardial distensibility, as occur in hypertrophy or in demand
      ischemia, have usually been attributed to a diastolic resurgence of cross-bridge
      interaction. In hypertrophied and failing myocardium, the recent demonstrations
      of diastolic calcium release from the ryanodine receptor, of deficient diastolic
      calcium removal from the cytosol, and of enhanced myofilamentary calcium
      sensitivity support residual diastolic cross-bridge interaction. In demand
      ischemia, the role of calcium overload in the reduction of diastolic LV
      distensibility is less clear because of correction of the reduced diastolic LV
      distensibility by quick stretches but not by a calcium desensitizer. Simultaneous
      imposition in animal models of multiple molecular changes involving interstitial,
      cytoskeletal, and myofilamentary proteins could elucidate their relative
      importance for myocardial stiffness and lead to selective correction of diastolic
      LV dysfunction as a novel mode of heart-failure therapy.

PMID- 15991156
TI  - Exercise test-induced arrhythmias.
AB  - Exercise testing commonly used by clinicians to characterize cardiovascular risk
      by detecting myocardial ischemia and assessing response to exercise. However, a
      consensus has not previously existed regarding the significance of exercise test
      induced arrhythmias due to conflicting results from the available studies. Recent
      studies with longer follow-up and improved technology have therefore stimulated
      this current review of the topic. Despite the continued debate in the literature
      regarding the prognosis of ETIA in a general population, there is sufficient
      evidence to suggest that clinicians should closely evaluate and follow those
      patients with arrhythmias during exercise testing and aggressively modify risk
      factors for coronary artery disease.

PMID- 15991158
TI  - Late-onset primary gastric outlet obstruction--an unusual cause of growth
      retardation.
AB  - We describe our experience of 2 children and review 6 previously reported cases
      of late-onset primary gastric outlet obstruction. The patients presented with
      abdominal pain, recurrent nonbilious vomiting, and growth retardation after a
      variable period of normal food intake. There was no history of peptic ulceration
      and corrosive ingestion. Barium meal showed dilated stomach with delayed gastric
      emptying. Exploration demonstrated dilated stomach with no intrinsic or extrinsic
      mechanical obstruction at the pylorus. Heineke-Mikulicz pyloroplasty was
      curative. Patients improved postoperatively and started thriving. We propose
      etiology and the term pyloric achalasia for this late-onset functional gastric
      outlet obstruction.

PMID- 15991157
TI  - A novel Czech kindred with familial medullary thyroid carcinoma and
      Hirschsprung's disease.
AB  - PURPOSE: The RET proto-oncogene is involved in neural crest disorders. Activating
      germline mutations in the RET proto-oncogene cause the development of familial
      medullary thyroid carcinoma (FMTC) or medullary thyroid carcinoma (MTC) as a part
      of multiple endocrine neoplasia type 2 (MEN2) syndrome. Inactivating germline
      mutations in the RET proto-oncogene are detected in Hirschsprung's disease
      (HSCR). Only in a very small number of families are these 2 diseases expressed
      together. METHODS: This study presents a novel Czech kindred with FMTC-HSCR
      phenotype. Two family members (mother and daughter) were tested for RET germline
      mutations in exons 10, 11, 13, 14, 15, and 16. RESULTS: Direct fluorescent
      sequencing of genomic DNA revealed a heterozygous mutation in the RET proto
      oncogene in exon 10 at codon C609Y in both persons tested. This family was
      reclassified, thanks to genetic screening from the apparently sporadic MTC-HSCR
      to FMTC-HSCR. CONCLUSION: The germline mutation was detected because of the
      systematic genetic screening of the RET proto-oncogene, which is useful for
      genetic counseling of potential risk of HSCR and MTC in other family members.
      This family could be added to the small worldwide cohort of families with
      MEN2A/FMTC-HSCR.

PMID- 15991159
TI  - Giant cyst of the rete ovarii in a child.
AB  - The ovarian cysts are mostly nonneoplastic in children and could be categorized
      as follicular, simple, and corpus luteum cysts. Follicle cysts are the most
      common type in both neonates and older children. The rete ovarii rarely gives
      rise to cysts and to benign and malignant tumors. The rete cysts are most often
      found in postmenopausal women and have not been reported in children yet. We
      describe herein a case of giant rete cyst of ovary in an 11-year-old girl and
      discuss the clinical and histopathologic features of such cysts.

PMID- 15991160
TI  - Surgical repair of combined gastroschisis and sternal cleft.
AB  - We present a case of prenatally diagnosed gastroschisis combined with a sternal
      cleft, as well as the successful surgical management of this unusual condition.
      Successful management of gastroschisis combined with sternal cleft has not been
      reported before in the literature.

PMID- 15991161
TI  - Esophageal atresia and severe respiratory failure--cuffed pediatric tracheal
      tubes as an additional therapeutic option?
AB  - This article describes the use of a cuffed pediatric endotracheal tube occluding
      selectively the air leakage resulting from tracheoesophageal fistula in a preterm
      neonate with esophageal atresia and severe respiratory failure due to respiratory
      distress syndrome. The gastric distension resolved completely within 4 hours.
      Surgical correction was performed on the third day of life after respiratory
      stabilization.

PMID- 15991162
TI  - Aortoesophageal fistula--an unusual complication of esophagitis caused by
      Dieffenbachia ingestion.
AB  - Aortoesophageal fistula (AEF) is a rare and mostly lethal cause of upper
      gastrointestinal bleeding in children. We report a successful outcome of surgical
      treatment after resuscitation of a girl aged 12 1/2 years with AEF as a
      complication of esophagitis caused by Dieffenbachia ingestion. The girl ate a
      leaf of Dieffenbachia picta in a suicidal attempt. After 5 weeks of medical
      treatment of esophagitis, small blood-stained vomitus and melena appeared. Within
      a few hours, it was followed by a massive gastrointestinal bleeding leading to
      exsanguination. The girl survived despite the pitfalls in clinical presentation
      and errors in diagnostic approach and treatment. Emergency exploration of
      cervical esophagus, followed by laparotomy and thoracotomy, was performed in
      attempt to find the source of bleeding and to control it. Aortoesophageal fistula
      was located between the ascending aorta near the origin of the brachiocephalic
      trunk and thoracic esophagus. Resection of the fistula led to prompt circulatory
      stabilization. The common houseplant, Dieffenbachia picta, causes edematous
      swelling of mucus membranes when chewed. Dieffenbachia-caused esophagitis is very
      rare and this etiology of AEF has not been reported in children.

PMID- 15991163
TI  - Transillumination of H-type tracheoesophageal fistula using flexible miniature
      bronchoscopy: an innovative technique for operative localization.
AB  - Precise localization of the fistula is the most important step in the operative
      strategy for dealing with H-type tracheoesophageal fistula. Bronchoscopic
      cannulation of the fistula with a Fogarty or ureteric catheter has been
      recommended to aid ready identification, but it is not always successful. We
      report an innovative technique that permitted localization of H-type fistula
      intraoperatively. A flexible pediatric 2.2-mm bronchoscope (Olympus BF Type N20)
      was steered through a standard endotracheal tube, and the fistula tract was
      illuminated, making its identification and subsequent repair straightforward. We
      have successfully deployed this approach in 3 newborns. We recommend the
      technique to localize H-type fistula.

PMID- 15991164
TI  - Thoracoscopic ligation of a tracheoesophageal H-type fistula in a newborn.
AB  - An H-type fistula represents the isolated form of tracheoesophageal fistula, and
      it is relatively uncommon. Conventional thoracotomy is associated with
      significant late sequelae; scapula alata, scoliosis, and excessive scarring
      [Konkin DE, O'hali WA, Webber EM, Blair GK. Outcomes in esophageal atresia and
      tracheoesophageal fistula. J Pediatr Surg 2003;38:1726-9]. Thoracoscopic
      approaches avoid these consequences. Thoracoscopic repair of esophageal atresia,
      together with fistula ligation, has been performed earlier [van der Zee DC, Bax
      NM. Thoracoscopic repair of esophageal atresia with distal fistula. Surg Endosc
      2003;17:1065-7]. Thoracoscopic repair of H-type fistula was not attempted before.
      This is probably because most H-type fistulas are high enough to be accessible
      through a neck incision. Low fistulas are better approached via the thorax. To
      our knowledge, this is the first report of a thoracoscopic approach to an H-type
      tracheoesophageal fistula in a newborn.

PMID- 15991165
TI  - Small bowel perforation from unit rod posterior spinal fusion.
AB  - An unusual complication of bowel perforation after unit rod posterior spinal
      fusion and anterior spine release via a retroperitoneal approach is described.
      This complication has not been previously described. The pediatric surgical
      specialist should be aware of this consideration in the differential diagnosis of
      abdominal pain after unit rod posterior spinal fusion.

PMID- 15991166
TI  - Myofibroblastic tumor causing severe neonatal distress. Successful surgical
      resection after embolization.
AB  - This report describes a case of a term male 3.1 kg, normal delivery, 38 weeks of
      gestation with a record of hydramnios by prenatal sonography. He had fetal acute
      suffering and respiratory distress. The first radiographic study showed a mass
      filling the whole left thorax cage causing erosion of the inferior edge of the
      third rib. The mediastinum was displaced to the right. Computed tomography scan
      confirmed a homogeneous tumor that filled the left thorax and displaced the
      mediastinum to the right without invasion. Surgical biopsy informed of a highly
      vascularized mesenchymal tumor. The tumor was embolized with Ivalon
      microparticles obtaining a nearly avascular mass. Complete surgical excision was
      made, including the whole mass and costal segments. Microscopically, it was an
      inflammatory myofibroblastic tumor. It was composed mainly of spindle-shaped
      cells without malignant features. On immunohistochemistry, the tumor showed
      positive staining for vimentin, whereas antidesmin antibodies and S-100 protein
      were negative. The aim of this article is to present an extremely uncommon case
      of neonatal distress caused by an intrathoracic, extrapulmonary myofibroblastic
      tumor. Complete surgical resection was possible after embolization.

PMID- 15991167
TI  - Infants with repaired esophageal atresia and distal tracheoesophageal fistula
      with severe respiratory distress: is it tracheomalacia, reflux, or both?
AB  - AIM OF STUDY: Infants with repaired esophageal atresia and distal
      tracheoesophageal fistula (EA/TEF) are at risk for severe respiratory distress,
      which is related to tracheomalacia (TM), gastroesophageal reflux, or both. This
      usually mandates an operation for TM and/or a fundoplication procedure (FP).
      METHODS: We retrospectively performed a 26-year review of 288 patients with
      repaired EA/TEF. Research Ethic Board approval was obtained. RESULTS:
      Postoperatively, 22 (7.6%) infants with EA/TEF developed severe respiratory
      distress. Thirteen infants had an initial TM procedure and symptoms improved in 7
      (54%). The 6 (46%) remaining patients with ongoing respiratory symptoms required
      an FP. Nine infants had an initial FP and the symptoms improved in 6 (67%). The
      remaining 3 (33%) patients with ongoing respiratory symptoms required a TM
      procedure. All patients improved with the second procedure. Several clinical
      parameters were assessed among the 4 patient groups (FP only, FP followed by TM
      procedure, TM procedure only, and TM procedure followed by FP); there were no
      significant differences noted. CONCLUSIONS: Whereas 54% to 67% of infants
      improved with a TM procedure or FP, 33% to 46% required both surgical procedures.
      No clinical parameters were identified that could predict which procedure should
      be performed first.

PMID- 15991168
TI  - A decade of using intraluminal tracheal/bronchial stents in the management of
      tracheomalacia and/or bronchomalacia: is it better than aortopexy?
AB  - BACKGROUND: We compared the efficacy and clinical outcomes of aortopexy versus
      tracheal stents in the management of tracheomalacia. METHODS: A retrospective
      analysis of 25 consecutive patients undergoing aortopexy (n = 11; 8 boys, 3
      girls) or tracheal stents (n = 14; 9 boys, 5 girls) between 1993 and 2003 was
      performed. RESULTS: Both treatment groups, aortopexy versus stents, were
      comparable in their mean age of diagnosis, timing of intervention, surgical
      indications ("dying spell" or failed extubation), and previous underlying
      conditions. The operative time (190 vs 72 minutes) and blood loss (26 vs 0 mL)
      were significantly greater in aortopexy group (P < .01). There were no
      perioperative deaths in either group. Interestingly, 4 of 11 patients in the
      aortopexy group developed pericardial effusion (P < .01). With stents in place
      for a mean of 15 (range 2-41) months, 3 of 8 patients with stent removal had
      significant granulation tissue requiring further dilatation. No death was
      observed in aortopexy group, whereas 1 stent-related death and 1 cardiac arrest
      requiring median sternotomy occurred during stent removal in 44 and 32 months'
      follow-up, respectively. CONCLUSION: Both aortopexy and tracheal stents are
      effective treatment modalities in the management of tracheomalacia. However,
      although aortopexy is associated with early perioperative complications, tracheal
      stents are associated with higher failure rate and more severe stent-related
      morbidity and mortality.

PMID- 15991169
TI  - Inflammatory response in children after laparoscopic vs open Nissen
      fundoplication: randomized controlled trial.
AB  - We performed a randomized controlled trial to compare the inflammatory and immune
      responses to Nissen fundoplication in infants and children undergoing either open
      or laparoscopic surgery. METHODS: Forty children undergoing Nissen fundoplication
      were randomized to laparoscopy or open surgery using minimization with respect to
      age, neurologic status, and operating surgeon. Intraoperative and postoperative
      analgesias were standardized. Inflammatory markers (plasma malondialdehyde,
      nitrate plus nitrite level, and cytokines) and monocyte class II major
      histocompatibility complex expression were measured preoperatively, at end of
      surgery, 4, 24, and 48 hours postoperatively. Postoperative changes were compared
      between open and laparoscopic groups. RESULTS: There were no significant changes
      in circulating malondialdehyde, nitrates plus/ nitrite, interleukin-10, or tumor
      necrosis factor alpha in the postoperative period in either group. Interleukin-1
      receptor antagonist (IL-1rA) and IL-6 were significantly increased in both
      groups, with a tendency for greater elevation of IL-1rA in the open group.
      Monocyte major histocompatibility complex expression fell significantly in both
      groups; however, this fall appeared to be slightly more marked in the open group.
      CONCLUSIONS: The postoperative cytokine response is similar in children
      undergoing open and laparoscopic Nissen fundoplication. This trial indicates that
      laparoscopy may partly reduce postoperative immune suppression.

PMID- 15991170
TI  - Esophagogastric dissociation in the neurologically impaired: an alternative to
      fundoplication?
AB  - BACKGROUND/PURPOSE: Gastroesophageal reflux is common in children with severe
      neurological impairment. Fundoplication may produce symptomatic improvement but
      has a high failure rate. Esophagogastric dissociation (EGD) is an alternative
      procedure for treatment of gastroesophageal reflux. The aim of this study is to
      evaluate the results of EGD in our institution and compare them with a
      neurologically matched group of children who had Nissen fundoplication. METHODS:
      Twenty consecutive patients who had EGD were retrospectively evaluated and the
      results were compared with a neurologically matched group of 20 consecutive
      patients who had Nissen fundoplication. RESULTS: Twenty patients had EGD, 17 as a
      primary procedure. There was no operative mortality but 5 have died of other
      causes. Resolution of reflux-associated symptoms occurred in all patients. Of the
      15 survivors, 5 remain on antireflux medication. Twenty patients had
      fundoplication. There was no operative mortality, but 8 patients have died of
      other causes. Failure occurred in 5 patients necessitating further surgery. Of
      the 10 unreoperated survivors, 6 remain on antireflux medication. CONCLUSIONS:
      Esophagogastric dissociation is an effective antireflux procedure when compared
      with fundoplication. It has a lower failure rate. We recommend EGD as a primary
      procedure in selected children with severe neurological impairment.

PMID- 15991171
TI  - An injectable tissue-engineered embolus prevents luminal recanalization after
      vascular sclerotherapy.
AB  - BACKGROUND/PURPOSE: Sclerotherapy for vascular malformations is often limited by
      luminal recanalization. This study examined whether an injectable tissue
      engineered construct could prevent this complication in a rabbit model of venous
      sclerotherapy. METHODS: Ethanol sclerotherapy of a temporarily occluded jugular
      vein segment was performed in 46 rabbits, which were then divided into 3 groups.
      Group I (n = 16) had no further manipulations. In groups II (n = 15) and III (n =
      15), 0.5 mL collagen hydrogel was injected intraluminally, respectively, devoid
      of and seeded with autologous fibroblasts. At 1, 4, and 20 to 24 weeks
      postoperatively, vein segments were examined for patency and resected for
      histological evaluation. Statistical analysis was by Fisher's Exact test.
      RESULTS: All vein segments were occluded at 1 and 4 weeks in all groups, despite
      histological evidence of progressive endothelial ingrowth. However, at 20 to 24
      weeks, angiography demonstrated restoration of vessel patency in groups I (3/6)
      and II (3/5), but not in group III (0/6; P = .043), in which histology confirmed
      an obliterated lumen for all vessels. CONCLUSION: An injectable, fibroblast
      based, engineered construct prevents midterm to long-term recanalization in a
      leporine model of vascular sclerotherapy. This novel therapeutic approach may
      prevent recurrence of vascular malformations after sclerotherapy, thus reducing
      the need for repeated procedures and morbid operative resections.

PMID- 15991172
TI  - Pediatric major resuscitation--respiratory compromise as a criterion for
      mandatory surgeon presence.
AB  - The American College of Surgeons Committee on Trauma has indicated that there are
      minimum criteria for a trauma surgeon to respond to a major resuscitation (MR)
      within 15 minutes. These criteria have been required for children without
      significant data to support their validity. Our hypothesis is that prehospital
      intubation/respiratory compromise (IRC) as a criterion to define an MR will be an
      accurate predictor. METHODS: The trauma registry of a level I trauma center was
      used for data collection of age, injury severity score (ISS), IRC, mortality,
      hospital days, intensive care unit (ICU) days, and emergency operations. Chi2
      with Yates correction and Mann-Whitney rank-sum testing was used for statistical
      analysis expressed as mean +/- SEM. RESULTS: One hundred eighteen patients were
      encoded as MR. Forty patients had prehospital IRC and 78 patients did not. There
      were statistically significant differences seen in ISS, ICU length of stay, and
      mortality (P < .001). Forty-five percent of patients with IRC died. None of the
      patients without IRC died. CONCLUSION: Injured children with prehospital IRC are
      significantly more likely to die, have a higher ISS, and a longer ICU length of
      stay. Prehospital respiratory distress in injured children in our trauma system
      is a reasonable criterion to define an MR in children.

PMID- 15991173
TI  - Unsafe at any speed--kids riding all-terrain vehicles.
AB  - BACKGROUND: All-terrain vehicle (ATV) sales have climbed 89% in the last 5 years.
      We sought to determine if pediatric ATV accidents have increased in frequency and
      morbidity. METHODS: Medical records of children treated in our emergency unit for
      ATV accidents from 1993 to 2003 were reviewed. The 11 years were divided into 2
      periods, January 1993 to June 1998 and July 1998 to December 2003, to allow
      comparisons and analysis of trends over time. RESULTS: We treated 184 children,
      with 90% requiring admission. Comparing the first and second halves of the study,
      patients treated increased from 8.7 +/- 4.8 (mean +/- SD) to 24.5 +/- 11.1 per
      year (P < .01), patients requiring immediate operation increased from 4 (9%) of
      44 to 24 (17%) of 140, and patients with serious injuries (resulting in direct
      intensive care unit admission, immediate operation, or death) rose from 12 (27%)
      of 44 to 51 (36%) of 140. Patient age was 11.5 +/- 3.9 years. Sixty-eight percent
      of the children sustained multiple injuries and 50% required surgery. Only 35% of
      the children wore helmets. CONCLUSION: Over the 2 periods, there was a
      significant increase in number of patients treated, and considerable increases in
      serious injuries, and need for immediate operation. Despite inherent risks with
      riding ATVs, helmet use and patient age were remarkably low.

PMID- 15991174
TI  - Aggressive surgical therapy and radiotherapy for patients with high-risk
      neuroblastoma treated with rapid sequence tandem transplant.
AB  - BACKGROUND/PURPOSE: The treatment approach for patients with high-risk
      neuroblastoma has been one of dose intensification chemotherapy and aggressive
      treatment of the primary tumor. Local tumor control is examined in high-risk
      patients treated with tandem stem cell transplant, aggressive surgery, and
      selected radiation therapy (XRT). METHODS: Seventy-six patients with high-risk
      stage III/IV neuroblastoma were treated on a standard protocol incorporating
      aggressive surgical resection with or without local XRT followed by tandem high
      dose chemotherapy and stem cell rescue. Patients were evaluated for degree of
      surgical resection, site of progression, and outcome. RESULTS: Overall event-free
      survival for the series is 56%. Forty-eight had gross total resection, 12 had
      greater than 90% resection, 10 had 50% to 90% resection, and 6 had biopsy only or
      no surgery. Surgical complications occurred in 29% with no deaths. There were no
      isolated local failures. Two patients had local recurrence after gross total
      resection. Surgeon assessment of completeness of resection agreed with
      postoperative radiological findings 66% of the time. CONCLUSION: Aggressive
      surgical treatment with local XRT and myeloablative chemotherapy with stem cell
      rescue provides excellent local control in high-risk neuroblastoma, although
      distant failures, particularly osseous, remain a problem. Poor correlation exists
      between the surgeon's perception of completeness of resection and findings on
      postoperative imaging studies.

PMID- 15991175
TI  - P-selectin expression, neutrophil infiltration, and histologic injury in neonates
      with necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: P-selectin promotes adherence of leukocytes to the
      endothelium in inflammatory processes. The aim of this study was to investigate
      the expression of P-selectin and its role in the development of inflammation in
      neonates with necrotizing enterocolitis (NEC). METHODS: Twenty-nine intestinal
      specimens from 13 neonates with NEC and 7 control neonates with congenital
      gastrointestinal abnormalities were studied. Histologic damage,
      immunohistochemical expression of P-selectin, and polymorphonuclear cell
      infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used
      to compare grades. RESULTS: Expression of P-selectin was increased in NEC
      compared with controls in both medium-sized vessels (P = .03) and in the
      microcirculation (P = .03). P-selectin expression on medium-sized vessels
      correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin
      expression was greatest in areas of active inflammation but markedly lower in
      necrotic areas. The degree of polymorphonuclear cell infiltration strongly
      correlated with P-selectin expression on both medium-sized vessels (P = .004, r =
      0.513) and the microcirculation (P = .001, r = 0.578). CONCLUSIONS: Expression of
      P-selectin is increased in medium-sized vessels and in the microcirculation in
      intestinal specimens of neonates with NEC compared with neonatal controls.
      Expression of P-selectin is associated with the recruitment of polymorphonuclear
      cells and the severity of histologic injury, although P-selectin expression is
      lost in necrotic tissue.

PMID- 15991176
TI  - Using quantitative methods to improve the diagnostic workup for abdominal pain in
      children.
AB  - INTRODUCTION: The differential diagnosis of abdominal pain in children can be
      challenging. We applied quantitative decision-making methods to this process and
      sought to determine if their use provided measurable benefit. METHODS: After
      obtaining institutional review board approval, we recorded key elements of the
      history, physical examination, laboratory, and imaging evaluations along with the
      cost and the time spent in the emergency department (ED) for children presenting
      with abdominal pain. Initially, data were collected (group 1, n = 1366 patients)
      and then presented to the ED pediatricians. For subsequent patients, ED
      physicians received a sheet specific to that patient's age and sex reporting the
      most common diagnoses and the elements of the evaluation that had proven most
      useful (group 2, n = 624 patients). We compared the difference in length of stay
      and costs before and after intervention, between study groups, by age groups, and
      separately by sex using a 2-factor analysis of variance. RESULTS: The diagnostic
      workup cost less in boys aged 2 to 12 years after the intervention. In boys and
      girls older than 12 years, the cost trended lower. DISCUSSION: This study
      demonstrates that ED physicians equipped with specific information were able to
      complete their diagnostic evaluation of children presenting with abdominal pain
      at a lower cost.

PMID- 15991177
TI  - Long-term outcomes in total colonic aganglionosis: a 32-year experience.
AB  - BACKGROUND/METHODS: A 32-year retrospective review from 1972 to 2004 analyzed
      complications and long-term outcomes in children with total colonic aganglionosis
      (TCA) as they relate to the procedure performed. RESULTS: Thirty-six patients (27
      boys, 9 girls) had TCA. The level of aganglionosis was distal ileum (26), mid
      small bowel (8), midjejunum (1), and entire bowel (1). Enterostomy was performed
      in 35 of 36. Eight developed short bowel syndrome. Twenty-nine (81%) had a pull
      through at 15 +/- 6 months (modified Duhamel 20, Martin long Duhamel 4, and Soave
      5). Six had a Kimura patch. Postoperative complications (including enterocolitis)
      were more common after long Duhamel and Soave procedures. Seven (19%; 2 with
      Down's syndrome) died (3 early, 4 late) from pulmonary emboli (1), sepsis (1),
      fluid overload (1), viral illness (1), liver failure (1), arrhythmia (1), and
      total bowel aganglionosis (1). Mean follow-up was 11 +/- 9 years (range, 6 months
      29 years). Twenty-four (83%) of 29 patients exhibited growth by weight of 25% or
      more, 21 (91%) of 23 older than toddler age had 4 to 6 bowel movements per day,
      and 17 (81%) of 21 were continent. In 5 of 6, the Kimura patch provided
      functional benefit with proximal disease. CONCLUSION: Long-term survival was 81%.
      The highest morbidity occurred with long Duhamel or Soave procedures. The
      modified Duhamel is our procedure of choice in TCA. Bowel transplantation is an
      option for TCA with unadapted short bowel syndrome.

PMID- 15991178
TI  - Geographic information system localization of community-acquired MRSA soft tissue
      abscesses.
AB  - BACKGROUND: Soft tissue infections with methicillin-resistant Staphylococcus
      aureus (MRSA) pose an ever-increasing risk to children in the community. Although
      historically these infections were limited to children with prolonged
      hospitalization, the authors have seen an increase in community-acquired
      infections in children without identifiable risk factors. The goal of this study
      is to determine the incidence of truly community-acquired MRSA soft tissue
      infections in our community and geographically map regions of increased risk.
      METHODS: After obtaining the institutional review board's approval, a
      retrospective chart review was conducted on 195 patients records who underwent an
      incision and drainage of soft tissue infections from January 1, 2000, to December
      31, 2003. Thirteen patients were excluded from the study because no cultures were
      taken at the time of incision and drainage. RESULTS: The most common organism
      isolated from wound culture was S aureus , 40% (73/182), of which 45% (33/73)
      were MRSA. Eighty-one percent (27/33) of MRSA infections were in Springfield, 1
      of 18 towns represented in the patient population. Geographic information system
      analysis identified a significant MRSA cluster 1.96 km in diameter within the
      city of Springfield. CONCLUSIONS: Geography proved to be a significant risk
      factor for presenting with MRSA infection. Geographic maps of antibiotic
      resistance can be used to guide physician antibiotic selection before culture
      results are available. This has significant implications for the health care
      provider in proper antibiotic selection within the community.

PMID- 15991179
TI  - A study of 11,003 patients with hypertrophic pyloric stenosis and the association
      between surgeon and hospital volume and outcomes.
AB  - AIM: The availability of large clinical databases allows for careful evaluation
      of surgical practices, indicators of quality improvement, and cost. We used a
      large clinical database to compare the effect of surgeon and hospital volume for
      the care of children with hypertrophic pyloric stenosis (HPS). METHODS: Patients
      with International Classification of Diseases-9 codes for HPS and pyloromyotomy
      were selected from the 1994 to 2000 National Inpatient Samples database. Multiple
      and logistic regression models were used to evaluate the risk-adjusted
      association between provider volume and outcomes. RESULTS: Postoperative
      complications occurred in 2.71% of patients. Patients operated on by low- and
      intermediate-volume surgeons were more likely to have complications compared with
      those operated on by high-volume surgeons (95% confidence interval [CI], 1.25
      3.78 and 95% CI, 1.25-2.69, respectively). Patients operated at low-volume
      hospitals were 1.6 times more likely to have complications compared with those
      operated at intermediate- or high-volume hospitals (95% CI, 1.19-2.20).
      Procedures performed at high-volume hospitals were less expensive than those at
      intermediate-volume hospitals by a margin of 910 dollars (95% CI, 443-1377
      dollars). CONCLUSIONS: These data represent the largest study to date on the
      epidemiology, complication rate, and cost for care for HPS. Patients treated by
      both high-volume surgeons and at high-volume hospitals have improved outcomes at
      less cost.

PMID- 15991180
TI  - Supraumbilical pyloromyotomy: a unique indication for antimicrobial prophylaxis.
AB  - BACKGROUND: The umbilical fold incision for infantile hypertrophic pyloric
      stenosis provides a convenient exposure and cosmetically appealing scar. This
      study investigates the possible difference in infection rates between traditional
      and supraumbilical approaches for pyloromyotomy. METHODS: All patients who
      underwent pyloromyotomy for infantile hypertrophic pyloric stenosis at a tertiary
      pediatric hospital were reviewed. Baseline wound infection rate was determined
      through review of patients with right upper quadrant incisions (group 1). A
      nonrandomized comparison was performed between patients with a supraumbilical
      approach (group 2) and those undergoing supraumbilical incisions after
      prophylactic antibiotic administration (group 3). RESULTS: Complete records were
      reviewed on 384 patients over a 6-year period. Demographics and preoperative
      factors were similar among groups. The rate of infection in group 1 (n = 258) was
      2.3%. With introduction of the supraumbilical approach, there was a statistically
      significant increase in wound infection rate to 7.0% (chi 2 ; group 1 vs group 2,
      P < .05). The use of prophylactic antibiotics with a supraumbilical approach
      reduced this rate of infection back to 2.3% (chi 2 ; group 1 vs group 3, P < 1.0
      and group 2 [n = 85] vs group 3 [n = 42], P < .3). CONCLUSIONS: The risk of wound
      infection by classic pyloromyotomy of 2.3% is significantly increased with an
      open supraumbilical approach. The use of prophylactic antibiotics reduces this
      risk of wound infection.

PMID- 15991181
TI  - Elective intestinal operations in infants and children without mechanical bowel
      preparation: a pilot study.
AB  - BACKGROUND/PURPOSE: Preoperative mechanical bowel preparation (MBP) for elective
      intestinal operations has been a long accepted practice. However, MBP is often
      unpleasant and time-consuming for patients, and clinical trials in adults have
      not shown improved outcomes. We conducted this pilot study to test whether
      omitting MBP before elective intestinal operations in infants and children would
      increase the risk of infectious or anastomotic complications. METHODS:
      Retrospective review was performed of 143 patients who had an elective colon or
      distal small bowel procedure performed at our children's hospital between 1990
      and 2003. RESULTS: Thirty-three patients (No PREP) were managed by a single
      surgeon who routinely omitted MBP, whereas another 110 patients (PREP) were
      prepared with enemas, laxatives, or both. Both groups received 24 hours of
      preoperative dietary restriction to clear liquids and perioperative parenteral
      antibiotics. The No PREP group had one anastomotic leak and no wound infections,
      whereas the PREP group had 2 anastomotic leaks and 1 wound infection (P = .58).
      These results occurred despite greater duration of antibiotic therapy and
      incidence of delayed wound closures in the PREP group. CONCLUSION: The results of
      this pilot study suggest that omitting MBP before elective intestinal operations
      in infants and children carries no increased risk of infectious or anastomotic
      complications. Eliminating MBP may reduce health care costs and inconvenience to
      patients. These findings warrant a large, prospective, randomized clinical trial
      to validate our findings and to investigate further the necessity of MBP in the
      pediatric population.

PMID- 15991182
TI  - Murine neuroblastoma attenuates dendritic cell cysteine cysteine receptor 7
      (CCR7) expression.
AB  - BACKGROUND/PURPOSE: Dendritic cell (DC) migration from tumors to T-cell priming
      sites is critical in developing antitumor cytotoxicity. Cysteine cysteine
      receptor 7 (CCR7), a promigratory chemokine receptor, regulates DC recruitment to
      secondary lymphoid organs. Tumors may inhibit CCR7 expression to evade
      immunodetection. Previous work implicates impaired DC migration as a critical
      defect in immunity to neuroblastoma (NB). However, the mechanism has yet to be
      defined. We hypothesize that NB abrogates DC CCR7 expression and signaling,
      leading to decreased antitumor immunity. METHODS: A/J mice (N = 36) were injected
      with saline (control) or murine NB (TBJ) and bone marrow-derived DC were isolated
      at 7, 14, and 28 days. CCR7 expression was analyzed by polymerase chain reaction,
      Western blot, and flow cytometry. Cytometry data were analyzed using the paired
      Student's t test. RESULTS: Dendritic cells isolated from mice with NB had a 60%
      increase in CCR7 protein expression by flow cytometry compared with control mice
      at day 7. However, there was a 43% downregulation of CCR7 expression by DC from
      tumor-bearing mice compared with controls 2 weeks postinoculation (P < .005).
      These observations were confirmed by polymerase chain reaction and Western blot
      analysis. CONCLUSION: Neuroblastoma initially upregulates CCR7 expression by DC.
      However, with tumor progression, this chemokine is downregulated, likely leading
      to impaired DC migration. Immunotherapeutic strategies to bypass or augment CCR7
      dependent DC trafficking may improve survival for patients with aggressive
      disease.

PMID- 15991183
TI  - Survival in sentinel lymph node-positive pediatric melanoma.
AB  - BACKGROUND: Sentinel lymph node (SLN) status is the strongest predictor of
      survival in adult melanoma. However, the prognostic value of SLN status in
      children and adolescents with melanoma is unknown. METHODS: Records of 327
      patients aged 12 to 86 years undergoing SLN biopsy for melanoma or other
      melanocytic lesions were reviewed. A literature search identified additional
      patients younger than 21 years undergoing SLN biopsy for the same indications and
      these patients were combined with our series for meta-analysis. RESULTS: Sentinel
      lymph node metastases were found in 8 (40%) of 20 patients aged 12 to 20 years
      compared with 55 (18%) of 307 adults (P < .05). Median follow-up was 35 and 17
      months for the groups, respectively. Sentinel lymph node-positive pediatric
      patients did not recur, whereas 14 (25%) adults recurred within this period. Of
      the 55 adults, 5 (9.1%) have died of disease. Of the combined SLN-positive
      children and adolescents from the literature (total n = 25), only a single (4%)
      child recurred at 6 months. The difference in survival for adult and pediatric
      patients was significant. CONCLUSION: Pediatric patients have a higher incidence
      of SLN metastases than adults yet have a lower incidence of recurrence. Sentinel
      lymph node status does not predict early recurrence in pediatric patients with
      melanoma or atypical Spitz nevi.

PMID- 15991184
TI  - Attenuated Salmonella typhimurium invades and decreases tumor burden in
      neuroblastoma.
AB  - INTRODUCTION: We have previously shown that Salmonella elicits an antitumor
      response against hepatic adenocarcinomatous metastases. In vitro studies have
      demonstrated both intracellular invasion and proliferation of Salmonella within
      cultured neuroblastoma cells. We sought to demonstrate in vivo invasion,
      proliferation, and a potential antitumor response. METHODS: A murine model for
      retroperitoneal neuroblastoma was established with viable neuroblastoma cells. A
      green fluorescent protein (GFP--Clontech, Palo Alto, CA) gene was inserted into
      our attenuated Salmonella species via electroporation. Fourteen days after
      retroperitoneal injection, the Salmonella typhimurium-pGFP construct was
      administered and studied. In separate experiments, the antitumor effect against
      neuroblastoma was studied in controls, Salmonella lacking an interleukin 2 (IL-2)
      gene (Sal-NG), and Salmonella containing an IL-2 gene (Salmonella-pIL2 ).
      RESULTS: Consistent with previous reports, 74% of mice injected were found to
      have recognizable tumors. Salmonella was present within tumor cells. Average
      tumor volumes for control, Sal-NG, and Salmonella-pIL2 mice were 2024.3, 749.5,
      and 332.4 mm3 , respectively (P < .0001). Tumor weights for control, Sal-NG, and
      Salmonella-pIL2 mice were 2.218, 0.880, and 0.377 g, respectively (P < .0001).
      CONCLUSIONS: Attenuated Salmonella species can now be tracked via fluorescent
      microscopy within tumor cells. Furthermore, an 84% reduction in tumor burden was
      observed in those animals gavage fed Salmonella with the IL-2 gene.

PMID- 15991185
TI  - The rationale for nonsteroidal anti-inflammatory drug therapy for inflammatory
      myofibroblastic tumors: a Children's Oncology Group study.
AB  - BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are neoplasms that are
      highly vascularized, have an intermediate prognosis, and are associated with
      infiltration, obstruction, local recurrence, and rare metastasis. Resection of
      large IMTs can lead to substantial morbidity and even mortality. Anecdotal
      experience suggests that nonsteroidal anti-inflammatory drugs may eradicate large
      IMTs or shrink them to a more readily resectable size and configuration. To
      support the hypothesis that nonsteroidal anti-inflammatory drugs are
      antiangiogenic for IMTs by interfering with vascular endothelial growth factor
      (VEGF) signaling via cyclooxygenase 2 (COX-2) inhibition, IMT specimens were
      immunohistochemically examined for expression of COX-2 enzyme and VEGF. METHODS:
      The diagnosis of IMT was confirmed in all 18 cases comprising the study.
      Intensity of COX-2 and VEGF staining was graded, and staining uniformity was
      examined. ALK-1 protein expression, found in up to two thirds of IMTs, was also
      determined. RESULTS: COX-2 and VEGF expression were identified in all tissue
      examined, with staining intensity varying independently. ALK-1 protein expression
      was identified in 33% of specimens. Its presence was not related to the intensity
      of COX-2 or VEGF staining. CONCLUSIONS: Our data suggest that the mediators of
      angiogenesis, VEGF and COX-2, are present and may play an important role in the
      growth of IMTs.

PMID- 15991186
TI  - Management of postoperative infections after the minimally invasive pectus
      excavatum repair.
AB  - PURPOSE: Pectus excavatum is frequently repaired using the minimally invasive
      placement of a substernal bar (Nuss procedure). Infectious complications after
      the Nuss procedure are potentially devastating. To date, the management of
      postoperative infectious complications has not been well described. METHODS: A
      retrospective review of all patients (N = 168) who underwent the Nuss procedure
      from January 1, 1997, to October 1, 2003, at our institution was performed. Six
      patients (4%) had postoperative infections, and their medical records were
      reviewed. RESULTS: Of the 6 patients, 5 underwent operative drainage for wound
      abscesses that developed 2 to 76 weeks postoperatively. The other patient
      developed cellulitis 12 months postoperatively and was treated effectively with
      antibiotics alone. Recurrent infections were treated in 3 of 6 patients, one of
      whom eventually required removal of the bar resulting in a mild, residual pectus
      excavatum defect. One of 6 patients has had the substernal bar removed
      electively. The remaining 4 continue to be without clinically apparent infection
      at this time and are over 1 year removed from their infection. CONCLUSIONS:
      Although uncommon, infectious complications after the Nuss procedure require
      complex management strategies. Despite recurrent infection in some cases, most
      infectious complications occurring after the minimally invasive repair can be
      effectively treated without having to remove the substernal bar.

PMID- 15991187
TI  - American Academy of Pediatrics Section on Surgery hernia survey revisited.
AB  - BACKGROUND: The aim of the study was to describe current treatment and trends in
      surgical management of pediatric inguinal hernias (IHs), specifically
      contralateral exploration. METHODS: Surveys were sent to 599 Surgical Section
      members. Questions paralleled the 1993 American Academy of Pediatrics survey and
      addressed recent controversial topics. Statistical analysis by chi2 was
      performed. RESULTS: Three hundred ninety-five (66%) surveys returned. For full
      term boys with reducible IH, 79% (82%) repair electively, regardless of age or
      weight. For full-term girls with reducible ovary, 49% (27%) repair electively,
      36% (59%) next available slot, 5% (10%) emergently (P < .01). In former premature
      infants, 53% (65%) repair reducible IH when convenient, regardless of age. For
      unilaterally presenting IH, 44% (65%) routinely explore contralateral groins in
      boys 2 years or younger (P < .01); 47% (84%) routinely explore girls 4 years or
      younger (P < .01). No significant association between routine exploration
      patterns and years in practice, region of country, or training program
      affiliation was found. Laparoscopic evaluation for contralateral IH was reported
      by 37% (6%), (P < .01) 1993 results italicized. CONCLUSION: Reports of routine
      contralateral inguinal exploration had absolute decreases of 21% for boys 2 years
      or younger, 37% for girls 4 years or younger. There has been a shift toward
      elective repair for girls with reducible ovaries. Use of laparoscopy for
      diagnostic contralateral evaluation has increased dramatically.

PMID- 15991188
TI  - The role of enteral nutrition in the reversal of parenteral nutrition-associated
      liver dysfunction in infants.
AB  - BACKGROUND: Liver dysfunction in children dependent on parenteral nutrition (PN)
      is well established, and the extent of hyperbilirubinemia has been shown to
      correlate with morbidity and mortality. The aim of this study was to assess
      whether increasing provisions of enteral nutrition can improve PN-associated
      hyperbilirubinemia over time. METHODS: A retrospective review was conducted on
      infants in our institution's Short Bowel Syndrome Clinic from 1999 to 2004.
      Inclusion criteria included PN duration more than 1 month, serum direct bilirubin
      more than 3 mg/dL while on PN, and tolerance of full enteral nutrition with
      eventual discontinuation of PN. Paired t tests were used for statistical
      analyses. RESULTS: Twelve infants were identified with a PN duration of 5 +/- 1
      months. Five patients underwent liver biopsy while on PN, and histological
      evidence of cholestasis was found on all specimens. Peak total and direct
      bilirubin levels were 10.5 +/- 1.9 and 7.0 +/- 1.6 mg/dL, respectively, and
      occurred at time of PN discontinuation. Only 2 patients had improvement in serum
      bilirubin levels before initiation of full enteral nutrition. After initiation of
      full enteral nutrition and discontinuation of PN, all patients achieved permanent
      normalization of bilirubin levels by 4 months (P < .05) after a 1-month plateau
      phase. Alkaline phosphatase levels approached reference range within this time
      but were not significant. CONCLUSION: These data demonstrate for the first time
      that although PN-dependent infants can achieve normalization of marked
      hyperbilirubinemia with enteral nutrition, the improvement in liver function
      usually begins only after full enteral nutrition is tolerated and PN is
      withdrawn. These findings support the aggressive weaning of PN to enteral
      nutrition in infants with short bowel syndrome.

PMID- 15991189
TI  - Serial transverse enteroplasty is associated with successful short-term outcomes
      in infants with short bowel syndrome.
AB  - BACKGROUND: The serial transverse enteroplasty (STEP) has been shown to improve
      nutritional indices in an animal model of short bowel syndrome. The aim of this
      study was to review short-term surgical and nutritional outcomes in the first
      cohort of infants to undergo the STEP procedure at our institution. METHODS: All
      patients who underwent the STEP procedure during a 26-month period from February
      2002 to March 2004 were reviewed. Paired t tests were used for comparisons
      between values pre-STEP and post-STEP (P < .05 deemed significant). Data are
      expressed as mean and range. RESULTS: The STEP was performed on 5 patients,
      including 1 newborn. The STEP was used as a primary lengthening operation in 4
      patients. Intestinal length was significantly increased in all patients with 18
      (10-26) stapler applications. There were no perioperative complications and no
      evidence of intestinal leak or obstruction on routine postoperative contrast
      study. Nutritional follow-up was available on 3 subjects at 17 (11-26) months
      post-STEP. Percentage of enteral nutrition was significantly increased in these
      subjects (P < .05). One subject was fully weaned from total parenteral nutrition
      6 weeks after the STEP, and bilirubin in another patient with profound
      cholestasis who had been listed for liver-small bowel transplant normalized after
      the STEP. An additional patient, with established cirrhosis before operation,
      underwent successful liver-small bowel transplantation 8 months after intestinal
      lengthening. CONCLUSION: The STEP procedure is a simple bowel-lengthening
      procedure with promising early surgical and nutritional outcomes. Further data
      from a multicenter registry are needed to demonstrate its long-term efficacy.

PMID- 15991190
TI  - Evidence for active Wnt signaling during postresection intestinal adaptation.
AB  - BACKGROUND: In the intestine, Wnt proteins are powerful regulators of cell
      proliferation, differentiation, and adhesion. Mutations of the adenomatous
      polyposis coli (APC) gene elevate nuclear beta-catenin and provoke intestinal
      tumor formation. We sought to determine whether Wnt signaling is involved in
      adaptive response to massive small bowel resection (SBR). METHODS: Male Min mice
      with a mutation of the APC gene and wild-type controls underwent a 50% proximal
      SBR or sham operation. After 3 days, villus height, crypt depth, and rates of
      proliferation and apoptosis were recorded in the remnant ileum. RESULTS: After
      SBR, villus height and enterocyte proliferation were significantly greater in the
      Min mice. Western blotting demonstrated resection-induced increases in beta
      catenin, c-Myc, and E-cadherin after SBR, which was more pronounced in Min mice.
      CONCLUSIONS: Mutation of the APC gene and augmented Wnt signaling in the
      intestine results in an enhanced adaptive response to massive SBR. These data,
      for the first time, implicate an important role for Wnt signaling during the
      pathogenesis of resection-induced intestinal adaptation.

PMID- 15991192
TI  - Development of an artificial placenta: CO2 elimination and hemodynamics as a
      function of arteriovenous blood flow.
AB  - BACKGROUND: As a first step toward the development of an artificial placenta, we
      investigated the relationship between blood flow rate through an arteriovenous (A
      V) circuit/oxygenator and both CO2 elimination and hemodynamic stability in a
      small animal model. METHODS: Male New Zealand rabbits (N = 10) with an average
      weight of 2.7 +/- 0.2 kg were anesthetized, paralyzed, and heparinized before
      carotid-jugular cannulation. A tracheostomy tube, an arterial catheter, and an
      aortic flow probe were placed. Arteriovenous flow through a custom-made, low
      resistance, 0.5 m2 hollow fiber oxygenator was initiated. Oxygen sweep flow was
      maintained at 300 mL/min, whereas blood flow was controlled at 10 to 40 mL/(kg
      min). Ventilation was discontinued during each blood flow rate trial. Hemodynamic
      and preoxygenator and postoxygenator blood gas data were recorded 30 minutes
      after initiation of each flow rate. CO2 removal was the product of the oxygen
      sweep gas flow rate and the sweep flow exhaust CO2 content as determined by
      capnometry. Data were analyzed by analysis of variance with post hoc Dunnett's t
      test. RESULTS: CO2 removal increased and PaCO2 decreased as a function of A-V
      blood flow rate. Simultaneously, systolic blood pressure did not significantly
      change. CO2 removal was effective at device flows greater than 20% of cardiac
      output. CONCLUSION: In this rabbit model, A-V blood flows at 25% to 30% of
      cardiac output allow full gas exchange without hemodynamic compromise. This model
      raises the possibility of using A-V support and an artificial placenta in
      newborns with respiratory failure.

PMID- 15991191
TI  - Effect of nitric oxide on fibroblast growth factor-10 and bone morphogenetic
      protein 4 expressions in the branching morphogenesis of fetal rat lung explants.
AB  - PURPOSE: Nitric oxide (NO) can accelerate branching morphogenesis of fetal rat
      lung explants in vitro, whereas its exact mechanism remains unclear. In this
      study, we investigate the effect of NO on the expression of fibroblast growth
      factor-10 (FGF10) and bone morphogenetic protein-4 (BMP4), which plays an
      important role in bud formation. METHODS: Fetal rat lungs harvested on day 13.5
      of gestation were cultured in serum-free medium for 72 hours with 0, 50, 100, and
      200 micromol/L of an NO donor, DETA NONOate (DETA/NO) (n = 4, 3, 6, and 5). The
      ratio of bud increment of each cultured lung was calculated, and the FGF10 and
      BMP4 mRNA expression levels were analyzed by real-time reverse transcription
      polymerase chain reaction. RESULTS: Bud increment ratio was significantly
      increased in 50, 100, and 200 micromol/L DETA/NO (3.3 +/- 0.2, 3.0 +/- 0.3, and
      3.5 +/- 0.5) compared to controls (1.9 +/- 0.3) (P < .05). There was a
      significant increase in BMP4 mRNA expression in 100 micromol/L DETA/NO (190% +/-
      20%) compared to controls (100% +/- 30%) (P < .05), whereas FGF10 mRNA expression
      was not significantly different between each DETA/NO group and controls.
      CONCLUSION: The NO donor not only promotes branching of fetal lung explants but
      also upregulates expression of BMP4, which is an important regulator of branching
      morphogenesis.

PMID- 15991193
TI  - The ex utero intrapartum therapy procedure for high-risk fetal lung lesions.
AB  - BACKGROUND: Indications for the ex utero intrapartum therapy (EXIT) procedure
      have expanded to include any fetal anomaly in which resuscitation of the neonate
      may be compromised. METHODS: We reviewed the medical records of 9 patients after
      resection of lung lesions during the EXIT procedure. RESULTS: The mean
      gestational age at EXIT procedure was 35.4 weeks. All lung masses maintained
      large sizes late into gestation with mean mass volume/head circumference ratio of
      2.5 at presentation and 2.2 at EXIT. Seven of 9 fetuses demonstrated hydropic
      changes (n = 6) and/or polyhydramnios (n = 5), and underwent prenatal
      intervention including thoracentesis, thoracoamniotic shunt placement,
      amnioreduction, and/or betamethasone administration. Overall survival after EXIT
      for lung mass resection was 89%. The average time on placental bypass was 65
      minutes. Postnatal complications included reoperation for air leak (n = 1),
      reoperation for bleeding (n = 1), and death from sepsis and prematurity (n = 1).
      Venoarterial extracorporeal membrane oxygenation was used in 4 neonates for
      persistent pulmonary hypertension. Maternal prenatal complications included
      polyhydramnios (n = 5), preterm labor (n = 4), and chorioamnionitis (n = 1). One
      mother required perioperative blood transfusion. CONCLUSION: The EXIT procedure
      allows for controlled resection of large fetal lung lesions at delivery, avoiding
      acute respiratory decompensation related to mediastinal shift, air trapping, and
      compression of normal lung.

PMID- 15991194
TI  - Cardiac anomalies in patients with congenital diaphragmatic hernia and their
      prognosis: a report from the Congenital Diaphragmatic Hernia Study Group.
AB  - BACKGROUND/PURPOSE: Patients with congenital diaphragmatic hernia (CDH) are known
      to have associated cardiac anomalies. Data from the Congenital Diaphragmatic
      Hernia Study Group has allowed better definition of the types of heart defects
      (HDs) and survival for these patients. METHODS: Since 1995, 2636 patients were
      enrolled in the Congenital Diaphragmatic Hernia Study Group from 82 centers.
      Patients with hemodynamically significant HD, excluding patent ductus arteriosus
      (PDA); patent foramen ovale (PFO); and atrial septal defect (ASD), were selected.
      Cardiac anatomy and survival data for all patients were reviewed. RESULTS: Two
      hundred eighty (10.6%) patients had significant HDs: ventricular septal defect
      (VSD); (42.2%), aortic arch obstruction (15%), univentricular anatomy (13.9%),
      tetralogy of Fallot variants (11.1%), total anomalous pulmonary venous return
      (3.9%), double outlet right ventricle (RV) (3.2%), pulmonary stenosis (2.5%),
      transposition of the great arteries (2.5%), and various other defects in 5.7%.
      Survival for the entire group was 67.1%; survival for patients without HD was
      70.2% and for patients with HD was 41.1% (P < .001). Patients with biventricular
      cardiac anatomy had a 47% survival, whereas those with univentricular anatomy had
      a 5% survival (P < .001). CONCLUSION: Significant HD is associated with 10.6% of
      CDH. Survival for patients with HD is significantly lower than for patients with
      normal cardiac anatomy. Patients with CDH and univentricular cardiac anatomy have
      a poor prognosis.

PMID- 15991195
TI  - Extracorporeal membrane oxygenation in pediatric cardiac transplantation.
AB  - BACKGROUND: We reviewed a single institution experience with extracorporeal
      membrane oxygenation (ECMO) in the perioperative management of cardiac
      transplantation. METHODS: Of all pediatric cardiac transplant candidates (1984
      2003), patients requiring ECMO pretransplantation/posttransplantation were
      identified, with particular attention to use of ECMO as a bridge to
      transplantation. Parameters reviewed included proportionate survival, incidence
      of pre-ECMO cardiac arrest, ECMO duration, and United Network for Organ Sharing
      list time. RESULTS: Three hundred patients were listed for transplantation.
      Twenty-nine required ECMO: 18 pretransplant, 3 pretransplant and posttransplant,
      6 posttransplant, and 2 for delayed acute rejection. There were 21 bridge-to
      transplant candidates, of which 10 eventually transplanted with 60% survival; 11
      not transplanted had no survivors (P = .004). Thirteen of 21 had cardiac arrest
      pre-ECMO with 1 (8%) survivor; 8 of 21 had no arrest with 5 (63%) survivors (P =
      .014). Mean ECMO duration and United Network for Organ Sharing list times between
      transplanted and not transplanted were not significant. Nine received ECMO
      posttransplantation for cardiopulmonary support; 5 (56%) of 9 survived. Two
      patients supported with ECMO for rejection-related cardiovascular collapse
      survived. CONCLUSION: ECMO can bridge children to cardiac transplantation.
      Survival is significantly impaired in bridge-to-transplant candidates stratified
      by pre-ECMO cardiac arrest. ECMO can also help transition from cardiopulmonary
      bypass after transplantation and provide effective support during acute
      rejection.

PMID- 15991196
TI  - The contralateral inguinal hernia in children.

PMID- 15991197
TI  - Serial transverse enteroplasty.

PMID- 15991198
TI  - Palladium-catalyzed cross-coupling reactions in total synthesis.
AB  - In studying the evolution of organic chemistry and grasping its essence, one
      comes quickly to the conclusion that no other type of reaction plays as large a
      role in shaping this domain of science than carbon-carbon bond-forming reactions.
      The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples
      of such processes, and are among those which have undeniably exercised decisive
      roles in the last century in the emergence of chemical synthesis as we know it
      today. In the last quarter of the 20th century, a new family of carbon-carbon
      bond-forming reactions based on transition-metal catalysts evolved as powerful
      tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions
      are the most prominent. In this Review, highlights of a number of selected
      syntheses are discussed. The examples chosen demonstrate the enormous power of
      these processes in the art of total synthesis and underscore their future
      potential in chemical synthesis.

PMID- 15991199
TI  - Triatomic EP2 triangles (E=Ge, Sn, Pb) as mu2:eta3,eta3-bridging ligands.

PMID- 15991200
TI  - Zn- and Cd-metallothionein recombinant species from the most diverse phyla may
      contain sulfide (S2-) ligands.

PMID- 15991204
TI  - Molecular recognition: comparative study of a tunable host-guest system by using
      a fluorescent model system and collision-induced dissociation mass spectrometry
      on dendrimers.
AB  - Host-guest interactions between the periphery of adamantylurea-functionalized
      dendrimers (host) and ureido acetic acid derivatives (guest) were shown to be
      specific, strong and spatially well-defined. The binding becomes stronger when
      using phosphonic or sulfonic acid derivatives. In the present work we have
      quantified the binding constants for the host-guest interactions between two
      different host motifs and six different guest molecules. The host molecules,
      which resemble the periphery of a poly(propylene imine) dendrimer, have been
      fitted with an anthracene-based fluorescent probe. The two host motifs differ in
      terms of the length of the spacer between a tertiary amine and two ureido
      functionalities. The guest molecules all contain an acidic moiety (either a
      carboxylic acid, a phosphonic acid, or a sulfonic acid) and three of them also
      contain an ureido moiety capable of forming multiple hydrogen bonds to the hosts.
      The binding constants for all 12 host-guest complexes have been determined by
      using fluorescence titrations by monitoring the increase in fluorescence of the
      host upon protonation by the addition of the guest. The binding constants could
      be tuned by changing the design of the acidic part of the guest. The formation of
      hydrogen bonds gives, in all cases, higher association constants, demonstrating
      that the host is more than a proton sensor. The host with the longer spacer
      (propyl) shows higher association constants than the host with the shorter spacer
      (ethyl). The gain in association constants are higher when the urea function is
      added to the guests for the host with the longer spacer, indicating a better fit.
      Collision-induced dissociation mass spectrometry (CID-MS) is used to study the
      stability of the six motifs using the corresponding third generation dendrimer. A
      similar trend is found when the six different guests are compared.

PMID- 15991205
TI  - Heavy group 14 1,(n+2)-dimetallabicyclo[n.n.n]alkanes and 1,(n+2)
      dimetalla[n.n.n]propellanes: are they all realistic synthetic targets?
AB  - [n.n.n]Propellanes and bicyclo[n.n.n]alkanes (1</=n</=3) in which the bridgeheads
      and bridges are composed of different Group 14 elements will not be ideal
      homologues of the all-carbon propellanes and bicycloalkanes. We used quantum
      chemical calculations to conclude which of these could possibly be stable at
      ambient temperature. Structures, strain, and dimerization energies of
      [n.n.n]propellanes and bicyclo[n.n.n]alkanes with C-based tethers and with Si,
      Ge, or Sn at the bridgehead positions were calculated. The aptitude to add water
      was probed in selected cases. Comparisons were made with the analogous all-C
      propellanes and bicycloalkanes. All heavy 1,(n+2)-dimetallabicyclo[n.n.n]alkanes
      should be thermally stable and suitable synthetic targets, even though the
      moisture sensitivity of 1,3-dimetallabicyclo[1.1.1]pentanes increases as Group 14
      is descended. For 1,(n+2)-dimetalla[n.n.n]propellanes, the incompatibility
      between the tether and M--M bond lengths impacts strongly on structure and
      stability. At ambient temperature 1,3-disila[1.1.1]propellanes should oligomerize
      instantly upon formation, whereas 1,3-digerma- and 1,3-distanna[1.1.1]propellanes
      should be less prone to oligomerize and possibly isolable. The 1,4
      dimetalla[2.2.2]propellanes with M=Si-Sn have biradical ground states and can
      presumably only be observed under inert conditions at cryogenic temperatures.
      Finally, we predict that 1,5-disila[3.3.3]propellane will be persistent at
      ambient temperature, but 1,5-distanna[3.3.3]propellane should rapidly
      oligomerize.

PMID- 15991206
TI  - Fine-tuning the electronic properties of highly stable organometallic Cu(III)
      complexes containing monoanionic macrocyclic ligands.
AB  - A family of highly stable organometallic Cu(III) complexes with monoanionic
      triazamacrocyclic ligands (L(i)) with general formula [CuL(i)]+ have been
      prepared and isolated, and their structural, spectroscopic, and redox properties
      thoroughly investigated. The HL(i) ligands have been designed in order to
      understand and quantify the electronic effects exerted by electron donor and
      electron-withdrawing groups on either the aromatic ring or the central secondary
      amine or on both. In the solid state the Cu(III) complexes were mainly
      characterized by single-crystal X-ray diffraction analysis, whereas in solution
      their structural characterization was mainly based on 1H NMR spectroscopy given
      the diamagnetic nature of the d(8) square-planar Cu(III) complexes. Cyclic
      voltammetry together with 1H NMR and UV/Vis spectroscopy have allowed us to
      quantify the electronic effects exerted by the ligands on the Cu(III) metal
      center. A theoretical analysis of this family of Cu(III) complexes has also been
      undertaken by DFT calculations to gain a deeper insight into the electronic
      structure of these complexes, which has in turn allowed a greater understanding
      of the nature of the UV/Vis transitions as well as the molecular orbitals
      involved.

PMID- 15991207
TI  - High-affinity chelator thiols for switchable and oriented immobilization of
      histidine-tagged proteins: a generic platform for protein chip technologies.
AB  - Protein micro-/nanoarrays are becoming increasingly important in systematic
      approaches for the exploration of protein-protein interactions and dynamic
      protein networks, so there is a high demand for specific, generic, stable,
      uniform, and locally addressable protein immobilization on solid supports. Here
      we present multivalent metal-chelating thiols that are suitable for stable
      binding of histidine-tagged proteins on biocompatible self-assembled monolayers
      (SAMs). The architectures and physicochemical properties of these SAMs have been
      probed by various surface-sensitive techniques such as contact angle goniometry,
      ellipsometry, and infrared reflection-absorption spectroscopy. The specific
      molecular organization of proteins and protein complexes was demonstrated by
      surface plasmon resonance, confocal laser scanning, and atomic force microscopy.
      In contrast to the mono-NTA/His6 tag interaction, which has major drawbacks
      because of its low affinity and fast dissociation, drastically improved stability
      of protein binding by these multivalent chelator surfaces was observed. The
      immobilized histidine-tagged proteins are uniformly oriented and retain their
      function. At the same time, proteins can be removed from the chip surface under
      mild conditions (switchability). This new platform for switchable and oriented
      immobilization should assist proteome-wide wide analyses of protein-protein
      interactions as well as structural and single-molecule studies.

PMID- 15991208
TI  - Palladium pincer complex catalyzed cross-coupling of vinyl epoxides and
      aziridines with organoboronic acids.
AB  - Palladium-catalyzed cross-coupling of vinyl epoxides and aziridines with
      organoboronic acids was performed by using 0.5-2.5 mol % pincer-complex catalyst.
      The reactions proceed under mild conditions affording allyl alcohols and amines
      with high regioselectivity and in good to excellent yields. Under the applied
      reaction conditions aromatic chloro-, bromo- and iodo substituents are tolerated.
      Our results indicate that the mechanism of the pincer complex catalyzed and the
      corresponding palladium(0) catalyzed process is substantially different. It was
      concluded that the transformations proceed via transmetalation of the
      organoboronic acids to the pincer-complex catalyst followed by an S(N)2'-type
      opening of the vinyl epoxide or aziridine substrate. In this process the
      palladium atom is kept in oxidation state +2 under the entire catalytic process,
      and therefore oxidative side reactions can be avoided.

PMID- 15991209
TI  - A simple thermodynamic model for quantitatively addressing cooperativity in
      multicomponent self-assembly processes--Part 2: Extension to multimetallic
      helicates possessing different binding sites.
AB  - The extended site-binding model, which explicitly separates intramolecular
      interactions (i.e., intermetallic and interligand) from the successive binding of
      metal ions to polytopic receptors, is used for unravelling the self-assembly of
      trimetallic double-stranded Cu(I) and triple-stranded Eu(III) helicates. A
      thorough analysis of the available stability constants systematically shows that
      negatively cooperative processes operate, in strong contrast with previous
      reports invoking either statistical behaviours or positive cooperativity. Our
      results also highlight the need for combining successive generations of complexes
      with common binding units, but with increasing metallic nuclearities, for
      rationalizing and programming multicomponent supramolecular assemblies.

PMID- 15991210
TI  - A simple thermodynamic model for quantitatively addressing cooperativity in
      multicomponent self-assembly processes--part 1: Theoretical concepts and
      application to monometallic coordination complexes and bimetallic helicates
      possessing identical binding sites.
AB  - A thermodynamic model has been developed for quantitatively estimating
      cooperativity in supramolecular polymetallic [M(m)L(n)] assemblies, as the
      combination of two simple indexes measuring intermetallic (I(c)MM) and
      interligand (I(c)LL) interactions. The usual microscopic intermolecular metal
      ligand affinities (f(i)(M,L)) and intermetallic interaction parameters (uMM),
      adapted to the description of successive intermolecular binding of metal ions to
      a preorganized receptor, are completed with interligand interactions (uLL) and
      effective concentrations (c(eff)), accounting for the explicit free energy
      associated with the aggregation of the ligands forming the receptor. Application
      to standard monometallic pseudo-octahedral complexes [M(L)(n)(H2O)(6 - n)] (M =
      Co, Ni, Hf, L = ammonia, fluoride, imidazole, n = 1-6) systematically shows
      negative cooperativity (uLL < 1), which can be modulated by the electronic
      structures, charges, and sizes of the entering ligands and of the metal ions.
      Extension to the self-assembly of more sophisticated bimetallic helicates
      possessing identical binding sites is discussed, together with the origin of the
      positively cooperative formation of [Eu2(L3)3].

PMID- 15991211
TI  - Spirocyclic diaminocarbenes: synthesis, coordination chemistry, and investigation
      of their dimerization behavior.
AB  - Nonaromatic, "saturated", spirocyclic N-heterocyclic diaminocarbenes 11 can be
      obtained from spirocyclic imidazolidin-2-thiones 10 by reductive desulfurization
      with potassium. The unsymmetrically N,N'-substituted spirocyclic imidazolidin-2
      thiones were obtained by reaction of ketimines 9 with lithium N-butyl-N
      lithiomethyldithiocarbamate (6). 13C NMR spectroscopy revealed that the
      unsymmetrically N,N'-substituted spirocyclic imidazolidin-2-ylidene 11 a
      undergoes a slow, acid-catalyzed dimerization to give the enetetramine 11 a=11 a,
      which exists in two isomeric forms (syn and anti). This reaction is reversible
      under special circumstances. Carbenes of type 11 react with [W(CO)6] to yield air
      stable carbene complexes of type [W11(CO)5] (14). The molecular structures of two
      derivatives 14 a and 14 b were established by X-ray crystallography and show
      clear distortion of the five-membered N-heterocyclic ring, caused by the
      spirocyclic molecular structure of the carbene ligands of type 11.

PMID- 15991212
TI  - (Dimethylaminomethyl)trifluorosilane, Me2NCH2SiF3--a model for the alpha-effect
      in aminomethylsilanes.
AB  - F3SiCH2NMe2 was prepared as a model for the investigation of the nature of the
      alpha-effect in alpha-aminosilanes, by fluorination of Cl3SiCH2NMe2 with SbF3.
      Under less mild conditions Si--C bond cleavage was also observed, leading to the
      double adduct F4Si(Me2NCH2SiF3)2, which was characterised by a crystal structure
      analysis showing that the central SiF4 unit is connected to Me2NCH2SiF3 via SiN
      dative bonds and FSi contacts. F3SiCH2NMe2 was characterised by multinuclear NMR
      spectroscopy (1H, 13C, 15N, 19F and 29Si), gas-phase IR spectroscopy and mass
      spectrometry. It is a dimer in the crystal (X-ray diffraction, crystal grown in
      situ), held together by two Si--N dative bonds. In solution and in the gas phase
      the compound is monomeric. The structure of the free molecule, determined by gas
      phase electron diffraction, showed that, in contrast to former postulates, there
      are no attractive SiN interactions. Ab initio calculations have been carried out
      to explain the nature of the bonding. F3SiCH2NMe2 has an extremely flat bending
      potential for the Si-C-N angle; the high degree of charge transfer from the Si to
      the N atoms which occurs upon closing the Si-C-N angle is in the opposite
      direction to that expected for a dative bond. The topology of the electron
      density of F3SiCH2NMe2 was analysed. Solvent simulation calculations have shown
      virtually no structural dependence on the medium surrounding the molecule. The
      earlier postulate of Si-->N dative bonds in SiCN systems is discussed critically
      in light of the new results.

PMID- 15991213
TI  - A general strategy toward S-linked glycopeptides.

PMID- 15991214
TI  - Scale-up of natural product formation and isolation.

PMID- 15991215
TI  - Polyphenol profiles of apple juices.
AB  - Focusing on 17 constituents, the polyphenol profiles of juices freshly made from
      various dessert (n = 4) and cider apple cultivars (n = 7) as well as commercially
      available apple juices (n = 24) were investigated using high-performance liquid
      chromatography-photodiode array detection (HPLC-DAD) and (HPLC)-electrospray
      ionization-tandem mass spectrometry (ESI(neg)-MS/MS) analyses. Significant
      differences in the total polyphenol content as well as the profiles of the apple
      cultivars under study were observed. For dessert apples the total polyphenol
      content ranged from 154 to 178 mg/L, whereas for 'old' German cider apple
      cultivars 261-970 mg/L were determined. Boskoop showed the highest (970 mg/L) and
      Granny Smith the lowest (154 mg/L) polyphenol content of the freshly prepared
      samples under study. Hydroxycinnamic acids, with chlorogenic acid as dominating
      constituent, ranged from 57 to 68 mg/L as well as from 134-593 mg/L in juices
      made from dessert apples and that from cider apples, respectively. Dessert apple
      juices showed lower contents of dihydrochalcones (10-35 mg/L) and flavan-3-ols
      (50-95 mg/L) compared to that of cider apples (34-171 mg/L and 70-393 mg/L,
      respectively). Quercetin and its derivatives were found from 0.4-4 mg/L and 0.4
      27 mg/L in juices made from dessert apples and that of cider apples,
      respectively. Compared with freshly made juices, lower contents of polyphenols
      were determined in the commercial samples under study. Amounts ranging from 110
      459 mg/L, dominated by chlorogenic acid with concentrations from 53-217 mg/L,
      were determined. Information about cultivar-typical apple polyphenol content and
      profile is important for bioactivity studies and, consequently, essential for the
      development of consumer-relevant products with particular nutritional
      functionalities.

PMID- 15991216
TI  - In vitro enzymatic degradation of nanoparticles prepared from hydrophobically
      modified poly(gamma-glutamic acid).
AB  - Amphiphilic poly(gamma-glutamic acid) (gamma-PGA) was prepared by the
      introduction of L-phenylalanine ethylester (L-PAE) as a side chain. This gamma
      PGA-graft-L-PAE formed monodispersed nanoparticles in water. The particle size of
      the gamma-PGA nanoparticles could be controlled by the degree of L-PAE grafting.
      The hydrolytic degradation and enzymatic degradation by gamma-glutamyl
      transpeptidase (gamma-GTP) of these gamma-PGA nanoparticles was studied by gel
      permeation chromatography (GPC) and scanning electron microscopy (SEM). The
      hydrolysis ratio of gamma-PGA was found to decrease upon increasing the
      hydrophilicity of the gamma-PGA. The degradation of the gamma-PGA backbone by
      gamma-GTP resulted in a dramatic change in nanoparticle morphology. With
      increasing time, the gamma-PGA nanoparticles reduced in size and finally
      disappeared completely.Time-course of the changes in the morphology of the gamma
      PGA nanoparticles following incubation with gamma-glutamyl transpeptidase.

PMID- 15991217
TI  - PLGA-(L-Asp-alt-diol)(x)-PLGAs with different contents of pendant amino groups:
      synthesis and characterization.
AB  - A series of novel biodegradable multi-block copolymers PLGA-(L-Asp-alt-diol)(x)
      PLGA with pendant amino groups was synthesized by ring-opening polymerization of
      D,L-lactide/glycolide(D,L-LA/GA) (75/25) using poly(N-Cbz-L-Asp-alt-diol)s as
      macroinitiator and stannous octoate as catalyst, in which the N-Cbz-L-Asp
      represents N-carbobenzyloxy-L-aspartic acid and diols are ethylene glycol,
      triethylene glycol, PEG200, and PEG600, respectively. Their structures and
      properties were characterized by FTIR, (1)H NMR, DSC, GPC, and elemental analysis
      (EA). The contents of the L-Asp unit in the copolymers were increased from 12.9
      to 79.3 mmol.g(-1) with decreasing the chain length of the diol, while the glass
      transition temperatures of the copolymers were decreased from 27.1 to 11.7
      degrees C with increasing the chain length of the diol. Thus, the results in this
      study provide a way to prepare biomaterials with different L-Asp unit densities
      or different number of bioactive sites as well as different properties through
      adjusting the chain length of the diol. Synthesis of PLGA-(N-Cbz-L-Asp-alt
      diol)(x)-PLGA copolymers.

PMID- 15991218
TI  - Does "excessive" or "compulsive" best describe exercise as a symptom of bulimia
      nervosa?
AB  - OBJECTIVE: The criteria in the 4th ed. of the Diagnostic and Statistical Manual
      of Mental Disorders (DSM-IV; Washington, DC: American Psychiatric Association)
      for bulimia nervosa include "excessive exercise" as an inappropriate compensatory
      behavior, suggesting that it is the quantity of the physical activity that is
      symptomatic, rather than its quality. The current study evaluated the hypothesis
      that psychological commitment to exercise (compulsive quality) will be more
      predictive of disordered eating attitudes and behaviors than the amount of time
      devoted to exercise (excessive quantity). METHOD: Female (n = 162) and male (n =
      103) undergraduates completed the Eating Disorder Inventory (EDI) subscales, the
      Obligatory Exercise Questionnaire (OEQ), and questions to assess the duration and
      frequency of exercise. RESULTS: Using multivariate analysis, the OEQ score was a
      positive predictor of disordered eating attitudes and behaviors, and exercise
      time was a negative predictor. DISCUSSION: "Compulsive" may be a better
      description than "excessive" in characterizing exercise as a symptom of bulimia
      nervosa.

PMID- 15991219
TI  - Cognitive avoidance in the strategic processing of ego threats among eating
      disordered patients.
AB  - BACKGROUND: This study of strategic processing examined whether it is possible to
      demonstrate cognitive avoidance of ego threats in women with eating disorders,
      using a task that involves less automatic identification of threat cues. METHOD:
      Fifty eating-disordered (anorexic and bulimic) and 50 comparison women completed
      a task of strategic processing, assessing their speed of solving neutral, food
      related, and ego threat-related anagrams. RESULTS: Cognitive avoidance of threat
      related information was shown, but only among women with bulimic characteristics.
      The presence of bulimic behaviors (binging and vomiting) was the clearest factor
      associated with such avoidance. There was no evidence of avoidance of disorder
      related (food) cues. DISCUSSION: Research and therapeutic implications are
      discussed, including the potential utility of therapies that directly or
      indirectly address the schema-level representation of ego threats when working
      with eating pathology.

PMID- 15991220
TI  - Hematological malignancies in the island of Sardinia, 1974-1993: age and sex
      distributions and temporal changes in incidence.
AB  - We have collected, by an active retrospective survey, all the cases of
      hematologic malignancies (HM) newly diagnosed during the time period 1974-1993 in
      the resident population of Sardinia. Diagnosis was deemed valid, after
      consultation of clinical records, in more than 90% of the 7264 collected cases.
      The number of newly diagnosed cases by year more than doubled during the 20-year
      period investigated. This striking increase can be only partially accounted for
      by ageing of population. Indeed, age-specific and age-adjusted rates of most of
      HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid
      Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions.
      The observed increase in rates is likely, in a large part, to be fictitious, due
      to easier access to a health care system, which in the meantime, improved its
      diagnostic efficiency. This was particularly evident for Chronic Lymphocytic
      Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho
      proliferative disorders, but its relevance declined after 1984-1989. A likely
      true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and
      similarly, although to a lesser extent and more doubtful, for Myelodysplasias
      (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each
      type of HM presented age and sex distributions and age-adjusted rates that show
      only minor differences from those reported for other western countries. No
      argument emerged to suggest that any genetic peculiarities of the Sardinian
      population might have affected the occurrence of HM. The confounding effects of
      improved diagnostic efficiency have prevented a reliable assessment of influence
      on incidences of environmental and socio-economic changes that, in relatively
      recent times, have occurred in Sardinia.

PMID- 15991221
TI  - The changing face of HIV-associated lymphoma: what can we learn about optimal
      therapy inl the post highly active antiretroviral therapy era?
AB  - Epidemiological data indicate that the risk of developing non-Hodgkin lymphoma
      (NHL) in HIV positive individuals is related to age and CD4 count (i.e. degree of
      immunosuppression). The prognosis of patients with HIV-NHL has been shown to be
      linked to several features including age, stage, modified IPI, prior AIDS
      diagnosis, CD4 count, immunoblastic pathology, LDH, and HAART use. These features
      are, as would be expected, a mixture of prognostic factors relating to both the
      HIV, and to the NHL. Population studies indicate that the incidence of associated
      (HIV-NHL) may be reducing with the advent of HAART, although not all studies
      concur. However, most population-based studies have not as yet shown a
      significant improvement in the survival of patients with HIV-NHL with HAART. The
      optimal chemotherapy for these patients is unknown, although it is generally
      accepted that CNS prophylaxis is mandatory. There is currently no good evidence
      of any survival benefit with increased dose intensity from large RCT. However, it
      must be borne in mind that the large randomised studies comparing differing dose
      intensities were undertaken before the advent of effective HAART. There is some
      evidence that there may be a subset of good prognosis patients who may benefit
      from more intensive therapy. Given that the prognosis of patients with HIV can
      now be considerably improved with HAART, we cannot necessarily assume that the
      same results would apply with regard to chemotherapy dose intensity. There is
      some evidence that there is a survival benefit from the addition of HAART to
      chemotherapy, although this is retrospective. It is likely, however, that the
      reason for this is that the HAART improves the prognosis of the patients from
      their HIV, and therefore reduces the number of patients dying from other HIV
      related illnesses whilst in remission from their lymphoma, as was seen in large
      numbers of patients in the earlier chemotherapy trials. It must not be forgotten
      that the prognosis of the patient's NHL is intimately linked to their prognosis
      with respect to the HIV. Although the number of patients with HIV-NHL is
      currently few, there is a need for more trials of chemotherapy, particularly now
      in the HAART era, when the prognosis from the point of view of the HIV has
      improved so much. In particular, the issue of dose intensity needs revisiting for
      patients whose overall prognosis can be improved by commencing HAART. Patients
      with HIV-NHL should be managed at specialist centres, and where possible should
      be managed as part of RCT.

PMID- 15991222
TI  - Current and future use of hematopoietic growth factors in cancer medicine.
AB  - Myelosuppression, in particular neutropenia and anemia are serious complications
      of malignancy and its treatment. Neutropenia can make patients vulnerable to
      potentially life-threatening infection. It often results in dose reductions and
      delay of planned chemotherapy, which can have a significant detrimental effect on
      tumour response and survival. Anemia can be associated with a range of
      debilitating effects, which can severely impair patients' QOL. In addition, there
      is some evidence recognizing anemia as a poor prognostic indicator, associated
      with reduced treatment efficacy. Reduction in the duration and severity of
      neutropenia and anemia is possible by initiation of appropriate growth factors
      during the first and subsequent cycles of chemotherapy. New and improved growth
      factor support with agents such as pegfilgrastim and darbepoetin alfa has the
      potential to improve the management of chemotherapy-induced neutropenia and
      anemia further. Thrombopoietin is currently in clinical trials to assess its
      potential role in the treatment of thrombocytopenia in patients with cancer.

PMID- 15991223
TI  - Increased expression of AML1-a and acquired chromosomal abnormalities in
      childhood acute lymphoblastic leukemia.
AB  - A semi-quantitative expression analysis of both AML1-a and AML1-total was
      performed by RT-PCR in 19 children with acute lymphoblastic leukemia (ALL) at
      diagnosis. AML1-a expression was assessed in 16 bone marrow (BM) and 13
      peripheral blood (PB) samples whereas AML1-total was assessed in 17 BM and 16 PB
      samples. These analyses were also carried out in 15 PB samples of healthy
      controls. In addition, 18/19 patients were karyotyped: 11 had an unmodified
      constitutional karyotype (CK) and seven exhibited acquired chromosomal
      abnormalities (ACA). The expression of AML1-a was significantly increased in BM
      and PB when compared with the controls (p < 0.013 and p < 0.035, respectively). A
      significant increase was found in the expression of AML1-a in BM of the ACA group
      compared with the CK group (p < 0.0009). The expression of AML1-a in BM and PB
      showed a significant increase in the ACA group compared with controls (p <
      0.00001 and p < 0.012, respectively); in contrast, the CK group did not differ
      from the controls. These observations may mean that the increase of AML1-a
      favours the progression of leukemia.

PMID- 15991224
TI  - Synthesis of (R)- and (S)-3,3,3-trifluoro-2-phenylpropanoyl isocyanates and their
      use as reactive analogues of Mosher's acid.
AB  - The title compounds have been prepared from the respective 3,3,3-trifluoro-2
      methoxy-2-phenylpropanoic acids (MTPA) by a three-step synthesis with MTPA
      chloride and MTPA amide as reaction intermediates. The requested compounds were
      obtained in high chemical yields without any change in optical purity during the
      preparation. To ascertain the usefulness of this auxiliary agent in the chiral
      analysis, isomeric 3,3,3-trifluoro-2-phenylpropanoyl isocyanates were subjected
      in NMR tubes to noncatalyzed reactions with 16 different commercially available
      chiral alcohols. The steric arrangement of all diastereomers prepared correlated
      well with their NMR spectral nonequivalence data (Deltadelta), thus demonstrating
      the regular sign distribution of Deltadelta of particular groups according to the
      devised molecular model. The usefulness of the novel derivatization is discussed.

PMID- 15991225
TI  - Conformational response of tartaric acid to derivatization: role of 1,3-dipole
      dipole interactions.
AB  - The four-carbon chain in (R,R)-tartaric acid derivatives is predominantly
      antiperiplanar (trans) in the acid, its salts, esters, and NH-amides, while (-)
      synclinal (gauche) conformer is the most abundant in N,N'-tetraalkyltartramides.
      Trialkylsilylation or tert-butylation of the hydroxy groups at C2 and C3 does not
      appear to affect the conformational preference of NH-tartramides, but it does
      change the conformational equilibrium in the case of tartrates (toward (-)
      gauche) and N,N'-tetraalkyltartramides (toward trans), as judged from the NMR
      data. X-ray diffraction data point to the stabilizing role of antiparallel dipole
      dipole interactions due to the 1,3-CO/CH bonds. These interactions can be found
      in the trans and (-)-gauche conformers but are not possible for the (+)-gauche
      conformers of (R,R)-tartaric acid derivatives. This rationalizes small proportion
      of (+)-gauche conformers in tartaric acid derivatives and points to a
      significance of 1,3-dipole-dipole interactions. The conformation around the C1-C2
      (and C3-C4) bond is different in tartrates (O-C-C=O, syn) and tartramides (O-C
      C=O, anti); the CD data (n-pi* band) show that O-silylation or O-tert-butylation
      brings about conformational changes around the C1-C2 bond in the case of N,N'
      tetraalkyldiamides only.

PMID- 15991226
TI  - Chiral nanotechnology.
AB  - A review of chiral, nanoscale science and technology is presented, with the
      subject divided into two topics. The first discusses nanotechnology in the
      service of asymmetric synthesis, chiral separations, and analysis. The second
      topic concerns broader research in the nanotechnology realm, where molecular
      chirality plays a role in the properties of materials, including molecular
      devices, chiral supramolecules, chiral nanotubes, chiral fullerenes, and DNA
      nanotechnology.

PMID- 15991227
TI  - Readily available pyridine- and quinoline-N-oxides as new organocatalysts for the
      enantioselective allylation of aromatic aldehydes with allyl(trichloro)silane.
AB  - The straightforward synthesis of a series of enantiomerically pure pyridine- and
      quinoline-N-oxides and their use as new organocatalysts for the enantioselective
      allylation of aromatic aldehydes with allyl(trichloro)silane is reported. The
      catalysts were readily assembled by combining commercially available enantiopure
      diamines with heterocyclic carboxylic acid N-oxides. The obtained compounds
      showed moderate to good chemical efficiency (up to 73% chemical yield) and
      satisfactory stereoselectivity (up to 50% ee). Tentative models of
      stereoselection were proposed to account for the stereochemical outcome of the
      reaction and to explain how the structural features of the catalyst control the
      stereoselctivity.

PMID- 15991228
TI  - Pregabalin-withdrawal encephalopathy and splenial edema: a link to high-altitude
      illness?
AB  - A postherpetic-neuralgia patient abruptly discontinued pregabalin. Thirty hours
      later, unexplained nausea, headache, and ataxia developed, progressing to
      delirium 8 days later. Magnetic resonance imaging indicated T2-hyperintense
      lesions of her splenium. Similar magnetic resonance imaging abnormalities,
      interpreted as focal vasogenic edema, develop in some epileptic patients after
      rapid anticonvulsant withdrawal. Patients with high-altitude cerebral edema have
      similar splenial-predominant magnetic resonance imaging abnormalities that
      accompany these same neurological symptoms. This case is the first to associate
      anticonvulsant-withdrawal splenial abnormalities with neurological symptoms, with
      gabapentin-type anticonvulsants, and is among the first in nonepileptic patients,
      suggesting that sudden anticonvulsant withdrawal alone, unaccompanied by
      seizures, can initiate symptomatic focal brain edema. The similarity of this
      syndrome to high-altitude cerebral edema suggests a possible common
      pathophysiology and offers potential therapies.

PMID- 15991229
TI  - Adhesive layer properties as a determinant of dentin bond strength.
AB  - The goal of this study is to evaluate the hypothesis that the properties of the
      resin adhesive might affect the microtensile bond strength (MTBS) of multibottle
      dental adhesive system. In order to alter the properties, the experimental resin
      adhesives containing 2,2-bis (4-2-hydroxy-3-methacryloyloxypropoxyphenyl)propane
      (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) at various ratios were
      prepared. Degree of conversion immediately after curing (DC-immed), degree of
      conversion at 48 h after curing (DC-48h) of a thin coat of the experimental
      adhesives, the flexural strength (FS) of the bulk specimens made of the
      experimental adhesives, pH, viscosity at shear rate of 1 S(-1), and the
      microtensile bond strength (MTBS) values of the adhesives to dentin were
      investigated. The maximum MTBS and FS values of the resin adhesives were observed
      when the ratio of Bis-GMA/TEGDMA was 60/40. However, pH and viscosity values
      increased with increasing Bis-GMA content in the adhesives. When Bis-GMA content
      was more than 60 wt %, the viscosity increased exponentially and restricted the
      DC and FS, and accordingly decreased the bond strength. The stronger the resin
      adhesives were, the higher the bond strength to dentin could be obtained.

PMID- 15991230
TI  - Synthesis of low-shrinkage polymerizable methacrylate liquid-crystal monomers.
AB  - As a part of the continuous pursuit to develop an ideal resinous dental
      restorative material for use in large posterior cavity restorations, this article
      reports the easy, high-yield synthesis and the incredibly low polymerization
      shrinkage property of a new bifunctional liquid crystal (LC) monomer. This new
      polymerizable nematic liquid crystal is the next higher homolog of the acrylate
      monomer reported in a previous work.1 It remains liquid crystalline between room
      and mouth temperatures and can be polymerized to isotropic polymer with the use
      of the same visible light inhibitor system as used with conventional monomers.
      The structure of this new monomer has been confirmed to be 2-(t-butyl), 1,4-bis
      [4-(6-methacryloxy-hexan-1-oxy)-benzoyloxy]-benzene. Unlike the synthesis of its
      acrylate homolog, when the same procedure is adopted for the synthesis of this
      compound, the recovery of the product is not split by a sizable amount of the by
      product. Therefore, the reaction is cleaner, with high yield and a less labor
      intensive purification procedure. Thus, the synthetic methodology has the
      potential for easy commercial scale-up. The monomer (V) polymerizes at room
      temperature with a shrinkage of about 2 vol %, as compared to > 8 vol % for
      conventional control (GTE), at similar degrees of conversion.

PMID- 15991231
TI  - Chemical or microbiological models of secondary caries development around
      different dental restorative materials.
AB  - This study evaluated artificial secondary caries around restorative materials,
      induced by means of chemical or microbiological models. The following materials
      were used randomly to restore 130 dental blocks: (1) zinc-oxide eugenol-free
      temporary filling: Coltosol (Coltene/Whaledent Inc.; n = 30), (2) silver amalgam:
      Permite C (SDI Limited, n = 20), (3) composite resin: Filtek Z250 (3M ESPE; n =
      20), (4) glass-ionomer cement: Fuji II (GC America Inc.; n = 20), (5) resin
      modified glass ionomer: Vitremer (3M ESPE; n = 20), and (6) polyacid modified
      resin: Dyract AP (Dentsply; n = 20). Ten specimens of Group 1 were kept in
      humidity, and had no carious formation (NC). Ten specimens of each group were
      submitted to pH cycling (CG, n = 60), and the others were immersed in a medium
      containing Streptococcus mutans and sucrose (BG, n = 60). Mineral content was
      determined by microhardness assessment, and lesion depth was measured in
      polarized light photomicrographs. In the chemical model (CG), mineral content
      values in the vicinities of restoration were high for Groups 5 (75.7 +/- 11.9), 4
      (70.8 +/- 14.2), and NC (95.4 +/- 3.8); intermediate for Groups 1 (55.8 +/-
      18.5), 6 (45.6 +/- 11.0), and 2 (44.3 +/- 11.2); and reduced for Group 3 (34.7 +/
      9.7). In the microbiological model (BG), results were similar to CG, although
      there was less demineralization. The highest lesion depths were found for Groups
      3 (182.3 +/- 33.2) in CG and 6 (126.5 +/- 42.8) in BG, when compared to Group 5
      (114.6 +/- 26.0 and 56.2 +/- 33.2, respectively). In both models of caries
      induction, ionomeric materials showed a superior cariostatic effect when compared
      to the other restorative materials.

PMID- 15991232
TI  - Structure modification of UHMWPE used for total joint replacements.
AB  - Modification of ultrahigh-molecular-weight polyethylene (UHMWPE) consisting of a
      combination of gamma irradiation and subsequent thermal treatment has been
      performed in order to investigate the resultant changes to its supramolecular
      structure. In the first step the polymer was irradiated by gamma rays at
      laboratory temperature under nitrogen. Five radiation doses (25, 50, 100, 150,
      and 200 kGy) were applied at two dose rates (0.25 and 2.5 kGy/h). In the second
      step the irradiated samples were thermally treated above the UHMWPE melting
      temperature. Insoluble fraction, crystallinity (fraction), and lamellar
      periodicity were determined as functions of dose and dose rate for irradiated
      samples before and after thermal treatment. Both modification steps were shown to
      produce substantial changes in the UHMWPE structure.

PMID- 15991233
TI  - Mechanical properties and in vitro degradation of bioresorbable fibers and
      expandable fiber-based stents.
AB  - Bioresorbable polymeric support devices (stents) are being developed in order to
      improve the biocompatibility and drug reservoir capacity of metal stents, as well
      as to offer a temporary alternative to permanent metallic stents. These temporary
      devices may be utilized for coronary, urethral, tracheal, and other applications.
      The present study focuses on the mechanical properties of bioresorbable fibers as
      well as stents developed from these fibers. Fibers made of poly(L-lactide)
      (PLLA), polydioxanone (PDS), and poly(glycolide-co-epsilon-caprolactone) (PGACL)
      were studied in vitro. These fibers combine a relatively high initial strength
      and modulus together with sufficient ductility and flexibility, and were
      therefore chosen for use in stents. The effect of degradation on the tensile
      mechanical properties and morphology of these fibers was examined. The expandable
      stents developed from these fibers demonstrated excellent initial radial
      compression strength. The PLLA stents exhibited excellent in vitro degradation
      resistance and can therefore support body conduits such as blood vessels for
      prolonged periods of time. PDS and PGACL stents can afford good support for 5 and
      2 weeks, respectively, and can therefore be utilized for short-term applications.
      The degradation resistance of the stents correlates with the profile of
      mechanical property deterioration of the corresponding bioresorbable fibers.

PMID- 15991234
TI  - Concurrent microscopic observations and activity measurements of cellulose
      hydrolyzing and methanogenic populations during the batch anaerobic digestion of
      crystalline cellulose.
AB  - This study compares process data with microscopic observations from an anaerobic
      digestion of organic particles. As the first part of the study, this article
      presents detailed observations of microbial biofilm architecture and structure in
      a 1.25-L batch digester where all particles are of an equal age. Microcrystalline
      cellulose was used as the sole carbon and energy source. The digestions were
      inoculated with either leachate from a 220-L anaerobic municipal solid waste
      digester or strained rumen contents from a fistulated cow. The hydrolysis rate,
      when normalized by the amount of cellulose remaining in the reactor, was found to
      reach a constant value 1 day after inoculation with rumen fluid, and 3 days after
      inoculating with digester leachate. A constant value of a mass specific
      hydrolysis rate is argued to represent full colonization of the cellulose surface
      and first-order kinetics only apply after this point. Additionally, the first
      order hydrolysis rate constant, once surfaces were saturated with biofilm, was
      found to be two times higher with a rumen inoculum, compared to a digester
      leachate inoculum. Images generated by fluorescence in situ hybridization (FISH)
      probing and confocal laser scanning microscopy show that the microbial
      communities involved in the anaerobic biodegradation process exist entirely
      within the biofilm. For the reactor conditions used in these experiments, the
      predominant methanogens exist in ball-shaped colonies within the biofilm.

PMID- 15991235
TI  - Quantitative polysome analysis identifies limitations in bacterial cell-free
      protein synthesis.
AB  - Cell-free protein synthesis (CFPS) is becoming increasingly used for protein
      production as yields increase and costs decrease. CFPS optimization efforts have
      focused primarily on energy supply and small molecule metabolism, though little
      is known about the protein synthesis machinery or what limits protein synthesis
      rates. Here, quantitative polysome profile analysis was used to characterize cell
      free translation, thereby elucidating many kinetic parameters. The ribosome
      concentration in Escherichia coli-based CFPS reactions was 1.6 +/- 0.1 microM,
      with 72 +/- 4% actively translating at maximal protein synthesis rate. A
      translation elongation rate of 1.5 +/- 0.2 amino acids per second per ribosome
      and an initiation rate of 8.2 x 10(-9) +/- 0.3 x 10(-9) M/s, which correlates to,
      on average, one initiation every 60 +/- 9 s per mRNA, were determined. The
      measured CFPS initiation and elongation rates are an order of magnitude lower
      than the in vivo rates and further analysis identified elongation as the major
      limitation. Adding purified elongation factors (EFs) to CFPS reactions increased
      the ribosome elongation rate and protein synthesis rates and yields, as well as
      the translation initiation rate, indicating a possible coupling between
      initiation and elongation. Further examination of translation initiation in the
      cell-free system showed that the first initiation on an mRNA is slower than
      subsequent initiations. Our results demonstrate that polysome analysis is a valid
      tool to characterize cell-free translation and to identify limiting steps, that
      dilution of translation factors is a limitation of CFPS, and that CFPS is a
      useful platform for making novel observations about translation.

PMID- 15991236
TI  - Change in UHMWPE properties of retrieved ceramic total knee prosthesis in
      clinical use for 23 years.
AB  - The alumina-ceramic total knee prosthesis developed by Kyocera Corp. was
      implanted in 1979, and was in clinical use for 23 years until total knee
      arthroplasty revision surgery in January 2002. It is believed that this is the
      longest clinical period of a ceramic total knee prosthesis reported to date in
      the world. In the present study, we gave consideration to the long-term clinical
      stability of the alumina-ceramic femoral component as well as the mechanism of in
      vivo degradation of ultrahigh molecular weight polyethylene (UHMWPE) based on the
      evaluated wear, oxidation, and fracture toughness of the retrieved UHMWPE. We
      concluded that the degradation of UHMWPE by progressive oxidation is an issue to
      be solved in the future. To moderate stress concentration, use of a thin UHMWPE
      insert should be avoided. The low wear rate and the mild wear pattern observed
      this time suggest the possibility of reduced wear of the UHMWPE against the
      alumina-ceramic femoral component, and the usefulness of the alumina-ceramic
      total knee prosthesis component was recognized even after long clinical use.

PMID- 15991237
TI  - Evaluation of load testing of postendodontic restorations in vitro: linear
      compressive loading, gradual cycling loading and chewing simulation.
AB  - This study introduces a modified dynamic testing mode with gradual load increase
      and examines whether this could be an alternative to customary methods of static
      loading or chewing simulation. Seventy-two extracted human maxillary root-canal
      treated central incisors were randomly divided into six groups with 12 teeth
      each. Three groups were restored with titanium posts cemented with chemically
      curing resin cement. The other three groups were restored with glass-fiber posts
      cemented with dual-curing composite cement. All teeth were capped with full
      ceramic crowns. Both kinds of restoration were tested by linear compressive
      (static) loading, a modified gradual (cycling) dynamic loading, and by chewing
      simulation followed by static loading until failure occurred. The maximum load
      capacity was recorded. Statistical comparison showed that maximum load capacities
      of the same post material obtained from gradual dynamic loading did not differ
      significantly from that of linear compressive loading or of chewing simulation.
      In contrast, comparisons of different post materials under static loading
      resulted in significantly different load capacities. Dynamic testing with gradual
      load increase can be considered an economic alternative for chewing simulation,
      because it provides equivalent results. Both procedures, however, imply different
      conclusions than static loading with respect to post materials.

PMID- 15991238
TI  - Mathematical modelling of a mixed culture cultivation process for the production
      of polyhydroxybutyrate.
AB  - Mixed cultures submitted to acetate "feast" and "famine" cycles are able to store
      intracellularly high quantities of polyhydroxybutyrate (PHB). It was demonstrated
      in a previous study that the intracellular PHB content can be increased up to
      78.5% (g HB/gVSS) of cell dry weight in a sequencing batch reactor (SBR) with
      optimised operating conditions. The specific PHB formation rate was also shown to
      be higher for mixed cultures than for pure cultures. Such high intracellular PHB
      contents and specific productivity open new perspectives for the industrial
      production of polyhydroxyalkanoates (PHA) using mixed cultures instead of pure
      cultures. The main goal in this work was to develop a mathematical model of mixed
      cultures envisaging the optimisation of PHB production. A relatively simple two
      compartments cell model was developed based on experimental observations and
      other models proposed in the literature. A convenient experimental planing
      allowed to identify the kinetic parameters and yield coefficients. Experiments
      were performed with and without ammonia limitation enabling the analysis of PHB
      formation independently of the cell growth process. The experimental true yields
      partially confirm the theoretical values proposed in the literature. The final
      model exhibited high accuracy in describing the process state of most experiments
      performed, thus opening good perspectives for future model-based optimisation
      studies.

PMID- 15991239
TI  - Variation in modes of chemotherapy administration for breast carcinoma and
      association with hospitalization for chemotherapy-related toxicity.
AB  - BACKGROUND: To the authors' knowledge, few studies to date have addressed the
      patterns of how chemotherapy was administered (administration modes) over time.
      In the current study, the goal of the authors was to describe how chemotherapy
      for breast carcinoma was administered and to determine whether chemotherapy
      administration modes were associated with toxicity in a community-based large
      cohort. METHODS: The authors studied 5256 women who were diagnosed with breast
      carcinoma at age 65 years or older between 1992-1999 and received chemotherapy.
      The patients were identified from the Surveillance, Epidemiology, and End Results
      (SEER)Program-Medicare linked databases. Chemotherapy drugs and modes of
      administration were determined through procedure codes in Medicare claims.
      RESULTS: Of the 5256 patients who received chemotherapy, 33% received it through
      an intravenous infusion for less than 1 hour; 39% through an intravenous infusion
      lasting 1-8 hours; 15% through an intravenous infusion lasting longer than 8
      hours and requiring a pump; 12% through an intravenous push technique; and 1%
      through a subcutaneous, intramuscular, or intralesional injection. These modes
      varied substantially across the 11 SEER areas. The risks of hospitalization for
      chemotherapy-related toxicities (neutropenia, fever, thrombocytopenia, and
      adverse effects of systemic therapy) were not found to be significantly
      associated with different modes of chemotherapy after adjusting for other
      factors. Compared with patients receiving 5-flurouracil using an intravenous
      infusion for longer than 8 hours, the risk of toxicity was determined to be 0.96
      (95% confidence interval [95% CI], 0.63-1.47) for patients treated with an
      intravenous infusion lasting 1-8 hours; 0.94 (95% CI, 0.62-1.41) for patients
      treated with an intravenous infusion lasting less than 1 hour; and 0.66 (95% CI,
      0.38-1.08) for patients treated with subcutaneous, intramuscular, or
      intralesional injection or an intravenous push technique. CONCLUSIONS: There were
      substantial geographic variations noted in the modes of administering
      chemotherapy; however, these variations did not appear to be associated with the
      risk of toxicities (neutropenia, fever, thrombocytopenia, and adverse effects of
      systemic therapy).

PMID- 15991240
TI  - Simple and alpha,beta-unsaturated aldehydes: correct prediction of genotoxic
      activity through structure-activity relationship models.
AB  - Aldehydes are widespread environmental and industrial compounds, able to
      stimulate a range of adverse health effects (e.g., general toxicity, allergenic
      reactions, mutagenicity, and carcinogenicity). We have previously presented
      quantitative structure-activity relationships (QSARs) for the genotoxicity of
      simple and alpha,beta-unsaturated aliphatic aldehydes. In this study, we show
      that the QSAR models are able to correctly predict--based only on the knowledge
      of the chemical structure--the genotoxicity of other aldehydes, not considered in
      the development phase of the models. This adds confidence to the reliability of
      our QSAR models as tools for the theoretical assessment of the genotoxic hazard
      posed by aldehydes. The analysis of SOS Chromotest induction ability and the ease
      of formation of DNA adducts by the aldehydes provided further mechanistic
      insights.

PMID- 15991241
TI  - DNA damage in lymphocytes of Indian rickshaw pullers as measured by the alkaline
      Comet assay.
AB  - Rickshaw pullers (RPs) engage in strenuous physical activity and are exposed to
      the air pollutants found in urban environments. Air pollutants and the reactive
      oxygen species generated by the physical activity both potentially can damage
      DNA. In the present study, the Comet assay, a sensitive tool for measuring DNA
      damage in single cells, was used to study genomic DNA damage in lymphocytes of
      Indian RPs. The study evaluated DNA damage in 118 healthy male volunteers,
      including 63 RPs whose work demanded high levels of physical activity for 7-9
      hr/day, and 55 controls matched for age, habits, socio-economic status, and
      exposure to air pollution. A significant increase was found for the mean Olive
      tail moment (arbitrary units) among the RPs (4.13 +/- 0.11; P < 0.001) in
      comparison with the controls (3.21 +/- 0.10). Likewise, comet tail length
      (microm) (RPs: 58.98 +/- 1.01 vs. controls: 52.38 +/- 1.24) and tail DNA (%)
      (RPs: 13.52 +/- 0.31 vs. controls: 10.04 +/- 0.24) were also significantly higher
      for RPs compared with those of their matched controls (both, P < 0.001). To our
      knowledge, this is the first demonstration that physical activity due to
      occupation can produce DNA damage in peripheral lymphocytes.

PMID- 15991242
TI  - Mouse lymphoma thymidine kinase gene mutation assay: follow-up meeting of the
      International Workshop on Genotoxicity Testing--Aberdeen, Scotland, 2003--Assay
      acceptance criteria, positive controls, and data evaluation.
AB  - The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on
      Genotoxicity Testing (IWGT), comprised of experts from Japan, Europe, and the
      United States, met on August 29, 2003, in Aberdeen, Scotland, United Kingdom.
      This meeting of the MLA Workgroup was devoted to reaching a consensus on the
      appropriate approach to data evaluation and on acceptance criteria for both the
      positive and negative/vehicle controls. The Workgroup reached consensus on the
      acceptance criteria for both the agar and microwell versions of the MLA.
      Recommendations include acceptable ranges for mutant frequency, cloning
      efficiency, and suspension growth of the negative/vehicle controls and on
      criteria to define an acceptable positive control response. The recommendation
      for the determination of a positive/negative test chemical response includes both
      the requirement that the response exceeds a defined value [the global evaluation
      factor (GEF)] and that there also be a positive dose-response (evaluated by an
      appropriate statistical method).

PMID- 15991243
TI  - Early prediction of tumor recurrence after curative resection of gastric
      carcinoma by measuring soluble E-cadherin.
AB  - BACKGROUND: Currently, to the authors' knowledge, there is no serum marker to
      predict disease recurrence after patients undergo curative resection for gastric
      carcinoma. Previous reports have indicated that serum levels of soluble E
      cadherin had prognostic value in these patients. The objective of the current
      study was to determine whether soluble E-cadherin levels could predict disease
      recurrence in patients with gastric carcinoma who underwent curative surgery.
      METHODS: Sixty-nine patients who underwent curative surgery for gastric carcinoma
      after December 1997 were followed prospectively. Venous blood samples were
      collected preoperatively, 1 month after surgery, and every 3 months thereafter.
      The blood samples were assayed for soluble E-cadherin and for carcinoembryonic
      antigen (CEA) using commercial enzyme-linked immunosorbent assay kits. Receiver
      operating characteristic (ROC) curves were used to define a cut-off level of E
      cadherin for the optimal sensitivity and specificity for predicting disease
      recurrence. RESULTS: The median follow-up was 21 months for patients with
      recurrent disease (n = 17 patients) and 36 months for patients without recurrent
      disease (n = 52 patients; P = 0.007). The optimal cut-off level of E-cadherin was
      10,000 ng/mL. The sensitivity for predicting prediction disease recurrence using
      this cut-off level at 3 months and at 6 months postsurgery was 47% and 59%
      respectively, which was significantly better compared with the sensitivity of CEA
      using the conventional cut-off level (6% at 3 months postsurgery and 6% at 6
      months postsurgery; P = 0.004 and P < 0.0001, respectively). The median time
      between the elevated E-cadherin level and documented disease recurrence was 13
      months (range, 3-20 months), compared with 4 months (range, 1-20 months) for CEA.
      CONCLUSIONS: Serum soluble E-cadherin was a good marker for predicting disease
      recurrence in the first 3-6 months after surgery, with a median of 13 months
      before clinical recurrence. The use of this marker may allow time for vigilant
      surveillance and consideration of adjuvant therapy.

PMID- 15991244
TI  - Determinants of human papillomavirus-negative, low-grade squamous intraepithelial
      lesions in the atypical squamous cells of undetermined significance/low-grade
      squamous intraepithelial lesions triage study (ALTS).
AB  - BACKGROUND: Although low-grade squamous intraepithelial lesions (LSIL) most often
      are the result of infection by human papillomaviruses (HPV), a small proportion
      of women with LSIL have negative HPV tests. Using the Atypical Squamous Cells of
      Undetermined Significance/LSIL Triage Study (ALTS) population, the authors
      evaluated the significance of HPV-negative LSIL. METHODS: Women with cytologic
      interpretations of LSIL by referral Papanicolaou (Pap) tests or enrollment
      ThinPrep tests (range, 1195-1476 women, depending on the specimen type and the
      reviewer) had HPV testing performed by both Hybrid Capture 2 and polymerase chain
      reaction (PCR)-based linear array for 27 HPV types. RESULTS: Using 4 independent
      cytologic definitions of LSIL, only 3-11% of women with LSIL were found to have
      HPV-negative results on both HPV tests. The demographic characteristics of women
      with HPV-negative LSIL were consistent with those of a low-risk population; many
      were age > 35 years, and many reported no or only 1 recent sexual partner. The
      absolute risk of a histologic diagnosis of cervical intraepithelial neoplasia
      (CIN) Grade 3/carcinoma during the 2-year trial was lower for women with HPV
      negative LSIL (range, 2-4%) compared with the absolute risks for oncogenic HPV
      positive women with LSIL (range, 13-19%). However, at the next 6-month follow-up
      visit, 12%-32% of the women with HPV-negative LSIL had a positive HPV test.
      Finally, visual inspection of cervigrams demonstrated a clear association between
      a larger os and negative HPV test results compared with women who had HPV
      positive LSIL. This may have influenced HPV sample adequacy. CONCLUSIONS: Based
      on the ALTS data, the authors found no evidence to support the existence of HPV
      negative LSIL as a distinct biologic entity related to the risk of cervical
      carcinoma. Such results appear to represent cytologic misinterpretations or
      falsely negative HPV tests.

PMID- 15991246
TI  - Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the
      human ovary.
AB  - Molecular targets of rapid non-genomic steroid actions are not well known
      compared to those of the classical transcription pathway, but ion channels have
      recently been identified to be steroid-sensitive. Especially, in the ovary, the
      very organ producing high amounts of sex steroids, their rapid actions are not
      well examined. We now identified a yet unknown target for sex steroids, a voltage
      dependent K+ channel (Kv4.2) that contributes to a transient outward K+ current
      (I(A)) in human granulosa cells (GCs). Sex steroid hormones at concentrations
      typical for the ovary (1 microM) blocked Kv4.2 thereby attenuating I(A) by about
      25% within seconds. We also found both Kv4.2 (KCND2) mRNA and protein in
      endocrine cells of the human and rhesus macaque ovary, emphasizing the
      physiological relevance of this channel. Therefore, we propose a role as fast
      responding steroid sensor for the Kv4.2 channel. The direct regulation of K+
      channel activity by sex steroids might represent a yet unknown mechanism of rapid
      steroid action in close proximity to the site of steroid production in the
      primate ovary. Our data might also be important for Kv4 channels in the brain and
      the cardiovascular system where rapid steroid effects are discussed in the
      context of prevention of cell death.

PMID- 15991247
TI  - BK-induced cytosolic phospholipase A2 expression via sequential PKC-delta,
      p42/p44 MAPK, and NF-kappaB activation in rat brain astrocytes.
AB  - Bradykinin (BK), an inflammatory mediator, has been shown to induce cytosolic
      phospholipase A2 (cPLA2) expression implicating in inflammatory responses in
      various cell types. However, the detailed mechanisms underlying BK-induced cPLA2
      expression in astrocytes remain unclear. RT-PCR and Western blotting analysis
      showed that BK induced the expression of cPLA2 mRNA and protein, which was
      inhibited by Hoe140, suggesting the involvement of B2 BK receptors, confirmed by
      immunofluorescence staining using anti-B2 BK receptor antibody. BK-induced cPLA2
      expression and phosphorylation of p42/p44 MAPK was attenuated by PD98059,
      indicating the involvement of MEK1/2-p42/p44 MAPK in these responses. BK-induced
      cPLA2 expression might be due to the translocation of NF-kappaB into nucleus
      which was inhibited by Hoe140, helenalin, and PD98059, implying the involvement
      of NF-kappaB. Moreover, BK-induced cPLA2 expression was attenuated by rottlerin,
      suggesting that PKC-delta might be involved in these responses. This hypothesis
      was supported by the transfection with a dominant negative plasmid of PKC-delta
      significantly attenuated BK-induced response. In addition, BK-stimulated
      translocation of PKC-delta from cytosol to membrane fraction was inhibited by
      rottlerin but not by PD98059, indicating that PKC-delta might be an upstream
      component of p42/p44 MAPK. Accordingly, BK-induced phosphorylation of p42/p44
      MAPK was attenuated by rottlerin but not by helenalin. These results suggest that
      in RBA-1 cells, BK-induced cPLA2 expression was sequentially mediated through
      activation of PKC-delta, p42/p44 MAPK, and NF-kappaB. Understanding the
      regulation of cPLA2 expression induced by BK in astrocytes might provide a new
      therapeutic strategy of brain injury and inflammatory diseases.

PMID- 15991248
TI  - 17-beta-estradiol elicits genomic and non-genomic responses in mouse male germ
      cells.
AB  - Estrogens have been postulated to exert a detrimental effect on spermatogenesis
      in vivo. Since mouse male germ cells express estrogen receptors, we have
      investigated whether molecular pathways are activated by estrogen stimulation of
      these cells. Our results demonstrate that estrogen receptor beta is expressed in
      mitotic and meiotic male germ cells as well as in the spermatogonia derived GC-1
      cell line. By using this cell line, we show that 17-beta-estradiol triggers
      activation of a transcriptional response that requires a functional estrogen
      receptor. Moreover, GC-1 cells respond to estrogens by transiently activating a
      signal transduction pathway that impinges on the mitogen-activated protein
      kinases (MAPK) ERK1 and -2. A similar dose-dependent transient activation of ERKs
      was also observed in primary mouse spermatocytes in culture. Activation by the
      estrogen was specific because other steroids such as progesterone and
      dihydrotestosterone were ineffective and because it could be blocked by the
      selective inhibitor of the ERK pathway and by competitive inhibitors of the
      estrogen receptor. Finally, we observed that 17-beta-estradiol does not affect
      spontaneous or induced apoptosis in cultured mouse spermatocytes, indicating that
      the apoptotic effects observed in vivo require additional testicular components.

PMID- 15991249
TI  - Heparan sulfates in skeletal muscle development and physiology.
AB  - Recent years have seen an emerging interest in the composition of the skeletal
      muscle extracellular matrix (ECM) and in the developmental and physiological
      roles of its constituents. Many cell surface-associated and ECM-embedded
      molecules occur in highly organized spatiotemporal patterns, suggesting important
      roles in the development and functioning of skeletal muscle. Glycans are
      historically underrepresented in the study of skeletal muscle ECM, even though
      studies from up to 30 years ago have demonstrated specific carbohydrates and
      glycoproteins to be concentrated in neuromuscular junctions (NMJs). Changes in
      glycan profile and distribution during myogenesis and synaptogenesis hint at an
      active involvement of glycoconjugates in muscle development. A modest amount of
      literature involves glycoconjugates in muscle ion housekeeping, but a recent
      surge of evidence indicates that glycosylation defects are causal for many
      congenital (neuro)muscular disorders, rendering glycosylation essential for
      skeletal muscle integrity. In this review, we focus on a single class of ECM
      resident glycans and their emerging roles in muscle development, physiology, and
      pathology: heparan sulfate proteoglycans (HSPGs), notably their heparan sulfate
      (HS) moiety.

PMID- 15991250
TI  - JC virus large T-antigen and IGF-I signaling system merge to affect DNA repair
      and genomic integrity.
AB  - The progression of cancer is often associated with genomic instability, which may
      develop as a result of compromised defense mechanisms responsible for the
      maintenance of chromosomal integrity. These include defects in telomere
      preservation, chromosomal segregation, and DNA repair. In this review, we discuss
      molecular interactions between viral and cellular signaling components, which
      interfere with DNA repair mechanisms, and possibly contribute to the development
      of a mutagenic phenotype. Our studies indicate that large T-antigen from the
      human polyomavirus JC (JCV T-antigen) inhibits homologous recombination directed
      DNA repair (HRR)-causing accumulation of mutations in the affected cells (JCP
      2005, in press). Surprisingly, T-antigen does not operate directly, but utilizes
      insulin receptor substrate 1 (IRS-1), which is the major signaling molecule for
      insulin-like growth factor I receptor (IGF-IR). Following T-antigen-mediated
      nuclear translocation, IRS-1 binds Rad51 at the site of damaged DNA. This T
      antigen-mediated inhibition of HRR does not function in cells lacking IRS-1, and
      can be reproduced in the absence of T-antigen by IRS-1 with an artificial nuclear
      localization signal. The interplay described between the IGF-IR signaling system
      and JCV T-antigen in the process of DNA repair could be relevant, since nearly
      90% of the human population is seropositive for JC virus, JCV T-antigen
      transforms cells in vitro, is tumorigenic in experimental animals, and the
      presence of JC virus has been shown in an increasing number of biopsies of human
      cancer.

PMID- 15991251
TI  - Nifedipine pretreatment reduces vibration-induced vascular damage.
AB  - A rat-tail vibration model of hand-arm vibration was employed to test whether
      preemptive administration of nifedipine (5 mg/kg) to block vasoconstriction
      prevents vibration-induced arterial damage. The tails of vibrated and nifedipine
      pretreated vibrated Sprague-Dawley rats were exposed continuously to 4 h of 60-HZ
      vibration at 49 m/s(2) rms. In nonvibrated anesthetized rats, the ventral tail
      arteries were bathed for 15 min in situ in 1 mM epinephrine or 1 mM
      norepinephrine to induce structural changes indicative of intense
      vasoconstriction. Arteries were processed for light and electron microscopy 45
      min after treatment. Compared to sham control, 4-h vibration significantly (P <
      0.01) reduced lumen size, generated endothelial disruption (7.0 +/- 2.6%),
      elevated nuclear factor of activated T cells c3 (NFATc3) expression in
      endothelial and smooth muscle cells, and increased smooth muscle cell
      vacuolization. The findings demonstrate that blockage of vibration-induced
      vasoconstriction with nifedipine prevents acute vascular damage. Smooth muscle
      and endothelial cells structurally altered by vasoconstriction are rendered
      susceptible to damage by vibration.

PMID- 15991252
TI  - Diabetic amyotrophy in an adolescent responsive to intravenous immunoglobulin.
AB  - We report the case of a 13-year-old boy with poorly controlled type 2 diabetes
      mellitus who developed severe diabetic amyotrophy, which progressed over a few
      months but demonstrated rapid recovery after administration of intravenous
      immunoglobulin. This report highlights the importance of monitoring adolescents
      for even the rare neurologic complications of diabetes mellitus most commonly
      encountered in adults, and supports the need for well-designed trials using
      immunomodulatory therapies in diabetic amyotrophy.

PMID- 15991253
TI  - Pharmacokinetics and bioavailability of a newly synthesized dihydropyridine
      compound with multidrug resistance reversal activity.
AB  - (+/-)3-(3-(4,4-diphenylpiperidin-1-yl)propyl) 5-methyl 4-(3,4-dimethoxyphenyl)
      2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate ((+/-)-DHP-014), is a new 4
      aryl-1,4-dihydropyridine that can reverse multidrug resistance mediated by the
      ATP-binding cassette (ABC) transport proteins, P-glycoprotein, multidrug
      resistance-associated protein 1 and breast cancer resistance protein; it exhibits
      negligible calcium channel blocking activity. The objective of this work was to
      investigate the pharmacokinetics of this new compound in rats. Three intravenous
      (1, 2 and 5 mg/kg) and two oral (25 and 50 mg/kg) doses were administered to
      female Sprague-Dawley rats. A two-compartment model with nonlinear elimination
      best characterized the pharmacokinetic profiles after intravenous and oral
      administration in rats. The terminal half-life of (+/-)-DHP-014 increased and the
      systemic clearance significantly decreased at higher doses, indicating nonlinear
      elimination. The dose-dependent clearance is likely due to saturation of
      metabolism. The apparent volume of distribution of (+/-)-DHP-014 was 2.0 L/kg in
      rats and was unchanged with increasing intravenous doses of (+/-)-DHP-014. The
      estimated oral bioavailability of (+/-)-DHP-014 was 8.2%. The poor
      bioavailability is likely due to the poor solubility of the compound, as well as
      to substantial first-pass elimination.

PMID- 15991255
TI  - In vivo DNA gene electro-transfer: a systematic analysis of different electrical
      parameters.
AB  - BACKGROUND: Intramuscular plasmid injection followed by electroporation is an
      efficient method for gene therapy or vaccination. Several protocols have been
      described that give good transduction levels with several reporter genes.
      METHODS: In this work we have explored the efficiency of gene delivery upon
      variation of the different electrical parameters such as pulse length frequency
      and voltage monitoring both on short- and long-term protein production. RESULTS:
      Having defined the best performing parameters, we have designed a short electric
      treatment that gives good levels of plasmid-encoded protein in different species
      such as mice, rabbits and monkeys.

PMID- 15991254
TI  - Inflammation and the etiology of type 2 diabetes.
AB  - Type 2 diabetes is increasingly common worldwide and is beginning to strike
      younger age groups. Almost 90% of all patients with diabetes show insulin
      resistance, which also precedes the first symptoms of diabetes. The mechanisms
      underlying the development of insulin resistance are not well understood. In
      recent years, several studies have been published that implicate subclinical
      chronic inflammation as an important pathogenetic factor in the development of
      insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis
      and treatment of early insulin resistance and incipient glucose intolerance.
      Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and
      TNF-alpha. Some antidiabetic agents, for example, glitazones that reduce insulin
      resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory
      drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often
      prescribed to people with diabetes, for example, statins and ACE
      inhibitors/angiotensin receptor antagonists, also counteract inflammation and
      reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should
      be identified, which may predict early disturbances in insulin sensitivity and
      cardiovascular risk. Also, inflammatory signalling pathways need to be explored
      in greater detail, and may form the basis of drugable targets against the
      epidemic of insulin resistance and atherosclerosis.

PMID- 15991256
TI  - Interspecies pharmacokinetic scaling of DA-8159, a new erectogenic, in mice,
      rats, rabbits and dogs, and prediction of human pharmacokinetics.
AB  - Time-averaged total body clearance (Cl) and apparent volume of distribution at
      steady state (V(SS)) of DA-8159 after intravenous administration to mice (30
      mg/kg), rats (30 mg/kg), rabbits (30 mg/kg) and dogs (3 mg/kg) were analysed as a
      function of species body weight (W) using the allometric equation for
      interspecies scaling, and were used to predict those in humans. Significant
      linear relationships were obtained between log Cl (l/h) and log W (kg) (r =
      0.992; p = 0.0079) and log V(SS) (l) and log W (kg) (r = 0.999; p < 0.0001). The
      corresponding allometric equations were Cl = 4.36 W(0.492) and V(SS) = 6.41
      W(0.911). These allometric equations were extrapolated to predict the Cl and
      V(SS) for DA-8159 in humans based on the 70 kg body weights. In addition,
      concentrations in the plasma-time profile predicted using the four animal data
      fitted to a complex Dedrick plot of animal data. Our results indicated that the
      DA-8159 data obtained from four laboratory animals could be utilized to generate
      preliminary estimates of the pharmacokinetic parameters in humans. These
      parameters can serve as guidelines for better planning of clinical studies.

PMID- 15991257
TI  - Gene transfer into adult rat spinal cord using naked plasmid DNA and ultrasound
      microbubbles.
AB  - BACKGROUND: Although gene therapy might become a promising approach to treat
      spinal cord injury, the safety issue is a serious consideration in human gene
      therapy. Plasmid DNA transfer is safer than viral vectors, but the transfection
      efficiency is quite low. To overcome the problem, we applied the ultrasound
      microbubbles-mediated transfection method to the spinal cord in adult rats, since
      ultrasound microbubbles have been reported to be efficient to increase
      transfection efficiency in various tissues. METHODS: After exposing T9-10 spinal
      cord with a laminectomy, we injected a mixture of naked plasmid DNA and
      microbubbles into cerebrospinal fluid by lumbar puncture. Then, the T9-10 spinal
      cord was exposed to ultrasound. CONCLUSIONS: An ultrasound intensity of 0.4-0.5
      W/cm2 significantly increased luciferase expression up to approximately 15-60
      fold at the insonated level as compared to naked plasmid DNA alone. Luciferase
      activity could be detected at least up to 7 days after transfection, while the
      expression level was almost returned to undetectable level at 14 days after
      transfection. The transfected cells were mainly meningeal cells in the surface of
      insonated spinal cord. There was no obvious evidence of worsening of neurological
      deficits as compared to rats transfected with naked plasmid DNA alone or
      untransfected rats. Similarly, successful gene transfer was also achieved in the
      insonated T9-10 spinal cord after spinal cord injury. Overall, the present study
      demonstrated the feasibility of ultrasound microbubbles-mediated plasmid DNA
      transfer into the target level of the spinal cord.

PMID- 15991258
TI  - Gene therapy flexes muscle.
AB  - This commentary highlights the promising results of recent studies in animal
      models of Duchenne muscular dystrophy and amyotrophic lateral sclerosis that have
      clearly demonstrated the potential of gene therapy for tackling these diseases.
      In the absence of effective drugs or other treatments, these advances in gene
      therapy technology represent the best hope for those patients and families that
      are blighted by these diseases. BACKGROUND: Diseases characterized by progressive
      muscle degeneration are often incurable and affect a relatively large number of
      individuals. The progressive deterioration of muscle function is like the sword
      of Damocles that constantly reminds patients suffering from these diseases of
      their tragic fate, since most of them will eventually die from cardiac or
      pulmonary dysfunction. Some of these disorders are due to mutations in genes that
      directly influence the integrity of muscle fibers, such as in Duchenne muscular
      dystrophy (DMD), a recessive X-linked genetic disease. Others result from a
      progressive neurodegeneration of the motoneurons that are essential for
      maintaining muscle function, such as in amyotrophic lateral sclerosis (ALS), also
      commonly known as Lou Gehrig's disease. The genetic basis of DMD is relatively
      well understood as it is due to mutations in the dystrophin gene that encodes the
      cognate sarcolemmal protein. In contrast, the cause of ALS is poorly defined,
      with the exception of some dominantly inherited familial cases of ALS that are
      due to gain-of-function mutations in the gene encoding superoxide dismutase
      (SODG93A). Gene therapy for these disorders has been hampered by the inability to
      achieve widespread gene transfer. Moreover, since familial ALS is due to a
      dominant gain-of-function mutation, inhibition of gene expression (rather than
      gene augmentation) would be required to correct the phenotype, which is
      particularly challenging.

PMID- 15991259
TI  - Executive function assessment of patients with schizophrenic disorder residual
      type in olanzapine treatment: an open study.
AB  - Cognitive deficits are a fundamental feature of the schizophrenic disorder, but
      the effect of antipsychotic treatment is still debated. The study assesses the
      effect of olanzapine on neurocognitive functioning and symptomatology of patients
      with schizophrenic disorder residual type. Executive function evaluation by the
      Wisconsin card sorting test (WCST) was performed on 39 patients treated with
      olanzapine (5-20 mg/day); the efficacy of drug in improving symptomatology,
      safety and quality of life was also evaluated. After 7 months of treatment, the
      mean number of WCST categories tended to increase. Correct responses increased
      with a statistically significant change from the baseline. The total and unique
      errors decreased significantly. At all post-baseline visits a decrease from
      baseline in the PANSS total, positive and negative scores was seen. The
      proportion of patients with less severe illness (CGI), increased over the course
      of the study with a corresponding decrease of patients with more severe illness.
      The quality of life scores also tended to improve during treatment. The Simpson
      Angus scale, Barnes-akathisia and abnormal involuntary movement scale scores
      decreased consistently. The most common treatment emergent drug related adverse
      events were weight gain, insomnia, agitation and anxiety. Neurocognitive
      functioning in terms of executive performance and symptomatology improved in
      people with schizophrenia residual type.

PMID- 15991260
TI  - One-year treatment of Alzheimer's disease with acetylcholinesterase inhibitors:
      improvement on ADAS-cog and TMT A, no change or worsening on other tests.
AB  - The aim of this study was to assess cognitive functioning measured by selected
      psychometric and neuropsychological tools in patients with Alzheimer's disease
      (AD) after 1-year treatment with acetylcholinesterase inhibitors. Seventy-six
      patients (22 male and 54 female) with a mild to moderate stage of AD, aged 56-86
      (mean 68) years, were treated. Forty-seven received donepezil (mean dose 9.3
      mg/d) and 29 rivastigmine (mean dose 8.5 mg/d). Cognitive measurements included:
      the mini mental state examination (MMSE), the Alzheimer disease assessment scale
      cognitive (ADAS- cog), the trail making test (TMT) and the Stroop color word
      interference test. The assessments were made before and after 3, 6 and 12 months
      of treatment. A significant improvement in ADAS-cog (p < 0.001, 83% of patients
      improved) and a worsening in MMSE (84% of patients worsened, p < 0.01 after 6 and
      12 months) was noted after the 1 year treatment. A majority of patients (57%)
      improved in the TMT-A (p < 0.001), measuring psychomotor speed and worsened in
      the TMT-B (p < 0.01, after 12 months), and Stroop B test (p < 0.001), measuring
      working memory and executive functions, 53% and 61%, respectively. Most patients
      (83%) did not change their performance in the Stroop A (improvement after 3
      months, p < 0.001, worsening after 6 and 12 months p < 0.01) test measuring
      verbal abilities, after 1 year treatment. The results obtained suggest that the
      treatment with cholinergic drugs may improve global cognitive functioning (ADAS
      cog) and psychomotor speed (TMT A), however, such treatment is unable to prevent
      the deterioration of working memory and executive functions.

PMID- 15991261
TI  - Protective effect of black tea extract on the levels of lipid peroxidation and
      antioxidant enzymes in liver of mice with pesticide-induced liver injury.
AB  - Sub-acute hepatotoxicity was induced in mice by exposure to pesticides. The
      effect of pretreatment with aqueous black tea extract on lipid peroxidation and
      antioxidants in the liver was investigated. Administering a combination dose of
      chlorpyriphos and cypermethrin (20 mg kg(-1) each) on alternate days over a 15
      day period to male mice resulted in induction of sub-acute toxicity as reflected
      by elevated levels of liver damage marker enzymes alkaline phosphatase(ALP),
      aspartate transaminase(AST) and alanine transaminase(ALT). Significantly elevated
      levels of lipid peroxidation were observed in the experimental group (group III)
      as compared with control mice. Decreased activities of superoxide dismutase
      (SOD), catalase (CAT), reduced glutathione (GSH), total thiol, glutathione
      peroxidase (GPx), glutathione reductase(GR) and glutathione-S-transferase (GST)
      were also observed in pesticide-treated as compared to control mice. Aqueous
      black tea extract was given as a pretreatment to group IV mice at a dose of 200
      mg ml(-1) polyphenols before the pesticide dose, which significantly decreased
      the levels of lipid peroxidation and significantly elevated the activities of
      SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the
      controls. Thus, the data offer support for the claim that the central mechanism
      of pesticide action occurs via changes in cellular oxidative status and shows
      conclusively that supplementation with black tea extract protects against the
      free radical-mediated oxidative stress in hepatocytes of animals with pesticide
      induced liver injury.

PMID- 15991262
TI  - Protective effect of aminoguanidine against oxidative stress in an experimental
      peritoneal adhesion model in rats.
AB  - Postoperative intraperitoneal adhesion formation is a major cause of intestinal
      obstruction, pain and infertility. This experimental study was designed to
      evaluate the degree of adhesion formation and peritoneal tissue levels of
      malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite and nitrate
      (NO) and the effect of aminoguanidine (AG) on these metabolite values after
      postoperative intraperitoneal adhesion formation in rats. A total of 21 adult
      male Wistar albino rats were randomly divided into three groups. Control rats
      were untreated; the AG group received AG 200 mg kg(-1) i.p. for 10 consecutive
      days intraperitoneally after surgery. The sham group was given 0.9% NaCl. The
      rats were killed on postoperative day 10. The peritoneal tissues were harvested
      to determine the tissue levels of MDA, GSH, and NO activity. For light
      microscopic evaluation, the cecum was removed. Adhesion formation scores in the
      AG group were significantly lower than those of the control and sham groups (p <
      0.017, p < 0.026 respectively). In the AG-treated rats, tissue levels of MDA and
      NO were significantly lower than in the control group (p < 0.017). The levels of
      GSH in aminoguanidine-treated rats were significantly higher than those of the
      control group (p < 0.01). The severity of the inflammation was more prominent in
      the control group compared with the AG-injected rats. The results demonstrate
      that in this experimental model, intraperitoneal administration of aminoguanidine
      decreases the incidence and extent of peritoneal adhesions and causes a decrease
      in MDA and NO and an increase in GSH values.

PMID- 15991263
TI  - Measuring the contribution of pharmacological treatment to advice to stay active
      in patients with subacute low-back pain: a randomised controlled trial.
AB  - PURPOSE: In clinical guidelines for acute and subacute low-back pain,
      pharmacological treatment is recommended for short-term symptomatic relief. The
      objective was to study the effect of the guidelines' advise to remain active,
      alone and with the addition of the drug adenosine tri-phosphate (ATP), in
      patients with subacute low-back pain. METHODS: A drug-guidelines effectiveness
      trial was undertaken simultaneously to an experimental drug efficacy placebo
      controlled trial in subacute (4-12 weeks) non-specific low-back pain patients.
      The 132 participating primary care physicians across France were randomised to
      participate to either trial. In the drug-guidelines trial, all physicians
      received a quick consultation card containing the key elements of the clinical
      guidelines and a brochure that gave their patients practical tips to remain
      active. Patients were then randomised to receive Atepadene, containing 90 mg of
      ATP by mouth daily for 30 days (guidelines plus ATP group), or nothing beside the
      rescue drug that was made available to all patients (guidelines alone group). The
      principal outcome was functional improvement on the Roland-Morris Disability
      Questionnaire (RDQ) at 90 days. RESULTS: In the drug-guidelines effectiveness
      trial, 157 patients were randomised. The rate of improvement in the RDQ over the
      90 days of follow-up was superior in the group guidelines plus ATP (8.3 points,
      95% confidence interval (CI): 7.3-9.3) than in the group guidelines alone (6.5
      points, 95%CI: 5.3-7.7) (p = 0.02). In terms of probability of improving between
      two to five points on the RDQ at 90 days this difference translated in a 2 to 13
      times higher probability compared to the group guidelines alone (odds ratios
      ranging from 2.1, 95%CI: 0.9-5.0 to 12.9, 95%CI: 1.6-103.4). Patients in the
      group guidelines plus ATP were also three times less likely to report a condition
      that had worsened or remained unimproved at 90 days (p = 0.02). CONCLUSION: This
      drug-guidelines effectiveness trial showed a modest advantage of combined
      specific pharmacologic and non-pharmacological treatments on absolute improvement
      on the RDQ. A threefold reduction in the risk of chronicity was observed, an
      important goal in low-back pain guidelines.

PMID- 15991265
TI  - Single-molecule fluorescence spectroscopy of protein folding.
AB  - Single-molecule spectroscopy is an important new approach for studying the
      intrinsically heterogeneous process of protein folding. This Review illustrates
      how different single-molecule fluorescence techniques have improved our
      understanding of mechanistic aspects in protein folding, exemplified by a series
      of recent experiments on a small protein.

PMID- 15991266
TI  - Electronic spectra of Ti(IV) in zeolites: an ab initio approach.

PMID- 15991267
TI  - Molecular recognition of dissolved pyrimidine derivatives by a dialkyl melamine
      type monolayer.

PMID- 15991269
TI  - Structure and properties of new ionic liquids based on alkyl- and
      alkenyltrifluoroborates.
AB  - A new series of low-melting, low-viscosity, hydrophilic ionic liquids, which
      comprise 1-ethyl-3-methylimidazolium ([EMI]+) and alkyl(alkenyl)trifluoroborate
      anions ([RBF3]-, R=n-C(m)H(2m+1) (m=1-5), CH2CH), were prepared and
      characterized. The phase-transition behavior, thermal stability, density,
      viscosity, conductivity, and surface tension of these salts were measured. The
      influence of the structural variations, such as changing the length and
      fluorination of the alkyl chain (R) in the anion [RBF3]-, on the above properties
      was extensively investigated. The low viscosity of these [RBF3]- salts suggests
      that a high degree of freedom and/or a somewhat flat-shaped feature in the anion
      make an important contribution to reducing the viscosity. The Walden products for
      each salt are not constant and vary with temperature, which suggests that the
      ions in these salts are not completely dissociated.

PMID- 15991268
TI  - The combination of intermediate doses of thalidomide and dexamethasone reduces
      bone marrow micro-vessel density but not serum levels of angiogenic cytokines in
      patients with refractory/relapsed multiple myeloma.
AB  - The aim of the study was the evaluation of anti-angiogenic activity of the
      combination of intermediate doses of thalidomide and dexamethasone in patients
      with refractory/relapsed myeloma. Twenty-five patients were included in the
      study. Microvessel density (MVD) was evaluated in marrow biopsies before and
      after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic
      fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), which
      have angiogenic potential and interleukin-6 (IL-6), IL-1beta, soluble IL-6
      receptor (sIL-6R), and transforming growth factor-beta (TGF-beta) which are
      involved in the disease biology, were measured before treatment and then every 2
      weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were
      increased in the patients compared to controls. The overall response rate to
      therapy was 72%. The administration of the combined regimen produced a
      significant reduction in MVD in responders. However, an increase in serum levels
      of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In
      contrast, serum levels of TNF-alpha, TGF-beta, IL-1beta did not differ between
      patients and controls and remained unchanged during the study. These results
      suggest that the combination of thalidomide plus dexamethasone is an effective
      treatment for myeloma reducing MVD marrow levels but not serum levels of
      angiogenic cytokines or cytokines implicated in myeloma biology.

PMID- 15991270
TI  - The structure of liquid methanol.
AB  - A combination of density functional calculations of molecular clusters with a
      quantum cluster equilibrium (QCE) model provides evidence that liquid methanol is
      dominated by cyclic and/or lasso structures. Only cluster populations including
      these structures fit the measured thermodynamic and spectroscopic properties,
      such as heat of vaporization, heat capacity, NMR chemical shifts, and quadrupole
      coupling constants. On the other hand, cluster populations comprising open-chain
      structures fail to reach the experimental values: the heat of vaporization is
      about 10 kJ mol(-1) too low, and the proton chemical shift is insufficiently
      downfield-shifted by about 1 ppm.

PMID- 15991271
TI  - Isotopic quantum effects in liquid methanol.
AB  - Density functional calculations (B3 LYP/6-31+G*) on molecular clusters and a
      quantum cluster equilibrium (QCE) model were used to calculate thermodynamic and
      structural properties of four isotopically labeled methanol species. The method
      allowed the reproduction of the characteristic differences in boiling points and
      heats of vaporization. Structural changes were also detected and related to
      recent experimental findings. It was shown that isotopic effects clearly have a
      quantum-mechanical origin.

PMID- 15991272
TI  - The oxidation state of a protein observed molecule-by-molecule.
AB  - We report the observation of the redox state of the blue copper protein azurin on
      the single-molecule level. The fluorescence of a small fluorophore attached to
      the protein is modulated by the change in absorption of the copper center via
      fluorescence resonance energy transfer (FRET). In our model system, the
      fluorescence label Cy5 was coupled to azurin from Pseudomonas aeruginosa via
      cysteine K27C. The Cy5 fluorescence was partially quenched by the absorption of
      the copper center of azurin in its oxidized state. In the reduced state,
      absorption is negligible, and thus no quenching occurs. We report on single
      molecule measurements, both in solution by using fluorescence correlation
      spectroscopy (FCS) combined with fluorescence intensity distribution analysis
      (FIDA), and on surfaces by using wide-field fluorescence microscopy.

PMID- 15991274
TI  - Role of Helicobacter pylori eradication in aspirin or non-steroidal anti
      inflammatory drug users.
AB  - Helicobacter pylori (H pylori) infection and the use of non-steroidal anti
      inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation
      represent well-established risk factors for the development of uncomplicated and
      complicated peptic ulcer disease accounting for the majority of such cases.
      Although the interaction between H pylori and NSAID/aspirin use in the same
      individuals was questioned in some epidemiological studies, it has now become
      widely accepted that they are at least independent risk factors for peptic ulcer
      disease. According to data from randomized intervention trials, naive NSAID users
      certainly benefit from testing for H pylori infection and, if positive, H pylori
      eradication therapy prior to the initiation of NSAID. A similar strategy is also
      suggested for naive aspirin users, although the efficacy of such an approach has
      not been evaluated yet. Strong data also support that chronic aspirin users with
      a recent ulcer complication should be tested for H pylori infection and, if
      positive, receive H pylori eradication therapy after ulcer healing, while they
      appear to benefit from additional long-term therapy with a proton pump inhibitor
      (PPI). A similar approach is often recommended to chronic aspirin users at a high
      risk of ulcer complication. H pylori eradication alone does not efficiently
      protect chronic NSAID users with a recent ulcer complication or those at a high
      risk, who certainly should be treated with long-term PPI therapy, but H pylori
      eradication may be additionally offered even in this setting. In contrast,
      testing for H pylori or PPI therapy is not recommended for chronic NSAID/aspirin
      users with no ulcer complications or those at a low risk of complications.

PMID- 15991275
TI  - Current preventive treatment for recurrence after curative hepatectomy for liver
      metastases of colorectal carcinoma: a literature review of randomized control
      trials.
AB  - To review the preventive approaches for recurrence after curative resection of
      hepatic metastases from colorectal carcinoma, we have summarized all available
      publications reporting randomized control trials (RCTs) covered in PubMed. The
      treatment approaches presented above include adjuvant intrahepatic arterial
      infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and
      immunotherapy. Although no standard treatment has been established, several
      approaches present promising results, which are both effective and tolerable in
      post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be
      regarded as effective and tolerable and it increases overall survival (OS) and
      disease-free survival (DFS) of patients, while 5-fluorouracil-based systemic
      chemotherapy has not shown any significant survival benefit. Fortunately
      chemotherapy combined with hepatic arterial infusion and intravenous infusion has
      shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have
      been conducted to evaluate its effect on prolonging survivals although many
      retrospective studies and case reports are published in which unresectable
      colorectal liver metastases are downstaged and made resectable with neoadjuvant
      chemotherapy. Liver resection supplemented with immunotherapy is associated with
      optimal results; however, it is also questioned by others. In conclusion, several
      adjuvant approaches have been studied for their efficacy on recurrence after
      hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric
      RCT is still needed for further evaluation on their efficacy and systemic or
      local toxicities. In addition, new adjuvant treatment should be investigated to
      provide more effective and tolerable methods for the patients with resectable
      hepatic metastases from CRC.

PMID- 15991276
TI  - Impact of simultaneous assay, the PCNA, cyclinD1, and DNA content with specimens
      before and after preoperative radiotherapy on prognosis of esophageal cancer
      possible incorporation into clinical TNM staging system.
AB  - AIM: The aim of the present study is to use immunohistochemical methods to
      investigate the clinical implications of tumor markers in esophageal squamous
      cell carcinoma and evaluate their impact on prognosis. METHODS: From November
      1990 to December 1996, 47 patients were treated with preoperative radiation
      followed by radical esophagectomy. All patients were confirmed pathologically as
      suffering from squamous cell carcinoma. Immunohistochemical stain was done for
      PCNA, cyclinD1 protein expression and DNA content analyzed by image cytometry.
      Kaplan-Meier method for single prognostic factor and log-rank test was used to
      test the significant difference. Cox stepwise regression model and prognosis
      index model were used for survival analysis with multiple prognostic factors.
      RESULTS: Radio-pathological change, T stage and N stage, as the traditional
      prognostic factors had statistical difference in 3-, 5- and 10-year survival
      rates. While, tumor cell proliferating marked PCNA, cyclinD1 and DNA content
      served as independent prognostic factors of esophageal carcinoma. There was
      definitely an identity between the single and multiple factor analyses. PI was
      more accurate to evaluate the prognosis of esophageal carcinoma. CONCLUSION: It
      is possible that tumor cell proliferating marked PCNA, cyclinD1 and DNA content
      would become the endpoints for evaluating the prognosis of esophageal carcinoma.

PMID- 15991277
TI  - Anti-cancer effect of iNOS inhibitor and its correlation with angiogenesis in
      gastric cancer.
AB  - AIM: To observe the anti-cancer effect of iNOS selective inhibitor
      (aminoguanidine, AG) and investigate the relationship between iNOS inhibitor and
      angiogenesis, infiltration or metastasis in MFC gastric cancer xenografts.
      METHODS: Fifty athymic mice xenograft models were established by inoculating
      gastric cancer cell MFC subcutaneously. Twenty-four hours later, 0.9% sodium
      chloride solution, mitomycin, low dosage AG, high dosage AG, mitomycin and AG
      were administered by intraperitoneal injection respectively. Thus these mice were
      divided into five groups of 10 each randomly: control group, MMC group, AG(L)
      group, AG(H) group, MMC+AG(H) group. Two weeks later the mice were killed, and
      the tumor weight, inhibitory rate were evaluated. Greiss assay was used to detect
      the nitric oxide levels in plasma. HE and immunohistochemistry staining were used
      to examine microvessel density (MVD) and the expression of iNOS, VEGF, and PCNA.
      Apoptosis was detected by using TUNEL assay. RESULTS: The inhibitory rates in
      MMC+AG(H) group and AG(H) group were 52.9% and 47.1% respectively, which is
      significant statistically compared with that of control group (0). In treatment
      groups, the cell proliferation index (PI) was lower and apoptosis index was
      higher than those of control group. Microvessel density, iNOS, and VEGF in MMC+
      AG(H) group were 8.8+/-2.6, 2.4+/-1.1, and 2.1+/-1.4 respectively, which is
      significant statistically compared with those of control group (68.3+/-10.6,
      11.3+/-1.3, and 10.3+/-1.6). The NO level in plasma of MMC+ AGH and AG(H) group
      were 12.7+/-2.1 and 12.9+/-2.0 mumol/L. Compared with that of control group
      (46.6+/-2.3 mumol/L), the difference is statistically significant. CONCLUSION: AG
      has anticancer effect on gastric cancer, and it has positive synergistic effect
      with chemotherapeutic drugs. It may play important inhibitory roles in
      angiogenesis of gastric cancer. The anticancer effect of iNOS inhibitors may
      include inducing cell apoptosis, suppressing cell proliferation and reducing
      angiogenesis.

PMID- 15991278
TI  - Effects of dietary intake and genetic factors on hypermethylation of the hMLH1
      gene promoter in gastric cancer.
AB  - AIM: Hypermethylation of the promoter of the hMLH1 gene, which plays an important
      role in mismatch repair during DNA replication, occurs in more than 30% of human
      gastric cancer tissues. The purpose of this study was to investigate the effects
      of environmental factors, genetic polymorphisms of major metabolic enzymes, and
      microsatellite instability on hypermethylation of the promoter of the hMLH1 gene
      in gastric cancer. METHODS: Data were obtained from a hospital-based, case
      control study of gastric cancer. One hundred and ten gastric cancer patients and
      220 age- and sex-matched control patients completed a structured questionnaire
      regarding their exposure to environmental risk factors. Hypermethylation of the
      hMLH1 gene promoter, polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2 and
      L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes
      were investigated. RESULTS: Both smoking and alcohol consumption were associated
      with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene
      promoter. High intake of vegetables and low intake of potato were associated with
      increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene
      promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L
      myc genes were not significantly associated with the risk of gastric cancer
      either with or without hypermethylation in the promoter of the hMLH1 gene.
      Hypermethylation of the hMLH1 promoter was significantly associated with
      microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed
      hypermethylation, whereas 28 of 94 (29.8%) the MSI-negative tumors were
      hypermethylated at the hMLH1 promoter region. Hypermethylation of the hMLH1 gene
      promoter was significantly inversely correlated with mutation of the p53 gene.
      CONCLUSION: These results suggest that cigarette smoking and alcohol consumption
      may influence the development of hMLH1-positive gastric cancer. Most dietary
      factors and polymorphisms of GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes
      are not independent risk factors for gastric cancer with hypermethylation of the
      hMLH1 promoter. These data also suggest that there could be two or more different
      molecular pathways in the development of gastric cancer, perhaps involving tumor
      suppression mechanisms or DNA mismatch repair.

PMID- 15991279
TI  - Use of Fourier-transform infrared spectroscopy to rapidly diagnose gastric
      endoscopic biopsies.
AB  - AIM: To determine if Fourier-transform infrared (FT-IR) spectroscopy of
      endoscopic biopsies could accurately diagnose gastritis and malignancy. METHODS:
      A total of 123 gastroscopic samples, including 11 cases of cancerous tissues, 63
      cases of chronic atrophic gastritis tissues, 47 cases of chronic superficial
      gastritis tissues and 2 cases of normal tissues, were obtained from the First
      Hospital of Xi'an Jiaotong University, China. A modified attenuated total
      reflectance (ATR) accessory was linked to a WQD-500 FT-IR spectrometer for
      spectral measurement followed by submission of the samples for pathologic
      analysis. The spectral characteristics for different types of gastroscopic
      tissues were summarized and correlated with the corresponding pathologic results.
      RESULTS: Distinct differences were observed in the FT-IR spectra of normal,
      atrophic gastritis, superficial gastritis and malignant gastric tissues. The
      sensitivity of FT-IR for detection of gastric cancer, chronic atrophic gastritis
      and superficial gastritis was 90.9%, 82.5%, 91.5%, and specificity was 97.3%,
      91.7%, 89.5% respectively. CONCLUSION: FT-IR spectroscopy can distinguish gastric
      inflammation from malignancy.

PMID- 15991280
TI  - Clinical significance of expression of apoptotic signal proteins in gastric
      carcinoma tissue.
AB  - AIM: To evaluate the expressions of apoptotic signal proteins FADD, TRADD, FasL,
      Fas, and NFkappaB in gastric carcinoma tissues and their clinical significance.
      METHODS: Western blot immune trace method was adopted to detect the expressions
      of apoptotic signal proteins FADD, TRADD, FasL, Fas, and NFkappaB in 55 tissue
      specimens of gastric carcinoma. RESULTS: Five apoptotic signal proteins had
      different expressions in the gastric carcinoma samples and their expressions were
      not correlated to age (P = 0.085). Expressions of the FADD, FasL, Fas, and
      NFkappaB proteins reduced with increase of the volume of tumor with the exception
      of increased expression the TRADD protein (64.7-71.1%, P = 0.031). With gradual
      increase of the malignancy of gastric carcinoma tissues, expressions of the FADD,
      FasL, and Fas proteins decreased (78.6-28.0%, P = 0.008; 78.6-65.9%, P = 0.071;
      100.0-46.3%, P = 0.014), while expressions of the TRADD and NFkappaB proteins
      increased (42.9-78.1%, P = 0.063; 78.6-79.1%, P = 0.134). With gradual increase
      of serum CEA, expression of the FADD protein decreased (62.5-34.0%, P = 0.073),
      but expressions of the TRADD, FasL, Fas, and NFkappaB proteins increased (0.0
      80.8%, P = 0.005; 62.5-70.2%, P = 0.093; 0.0-70.2%, P = 0.003; 62.5-80.9%, P =
      0.075). When compared to the tissues of gastric carcinoma without metastasis, the
      positive rate of expressions of the FADD and FasL proteins increased, whereas
      expressions of the TRADD, FADD, and NFkappaB proteins decreased. There was no
      significant difference between them (P = 0.095). CONCLUSION: Gastric carcinoma is
      endurable to Fas-related apoptosis and apoptotic signal proteins are differently
      expressed in gastric carcinoma.

PMID- 15991281
TI  - Expression and significance of tumor-related genes in HCC.
AB  - AIM: To investigate the expression and clinical significance of DEK, cyclin D1,
      insulin-like growth factor II (IGF-II), glypican 3 (GPC3), ribosomal
      phosphoprotein 0 (rpP0) mRNA in hepatocellular carcinoma (HCC) and its
      paraneoplastic tissues. METHODS: The expression of mRNAs of DEK, cyclin D1, IGF
      II, GPC3 and rpP0 mRNA was detected in HCC and its paraneoplastic tissues by
      multiplex RT-PCR. RESULTS: By the simplex RT-PCR, the overexpression of mRNAs of
      DEK, cyclin D1, IGF-II, GPC3, rpP0 mRNA in HCC and its paraneoplastic tissues was
      78.1%, 87.5%, 87.5%, 75.0%, 81.3% and 15.6%, 40.6%, 37.5%, 21.9%, 31.3%
      respectively (P<0.05). By the multiplex RT-PCR, at least one of the mRNAs was
      detected in all HCC samples and in 75.0% of paraneoplastic samples (P>0.05).
      However, all these five mRNAs were found in 68.8% of HCC samples, but only in
      9.4% of paraneoplastic tissues (P<0.05). The positive expression of mRNAs of DEK,
      cyclin D1, IGF-II, GPC3, rpP0 in well- and poorly-differentiated HCC was 89.0%,
      66.7%, 66.7%, 66.7%, 77.8% and 73.9%, 95.7%, 95.7%, 95.7%, 82.6%, respectively
      (P>0.05). The expression of these genes in HCCs with alpha-feto protein (AFP)
      negative and positive was 90.0%, 80.0%, 90.0%, 90.0%, 90.0% and 72.7%, 86.3%,
      77.3%, 90.9%, 68.2% respectively (P>0.05). CONCLUSION: The expression of DEK,
      cyclin D1, IGF-II, GPC3, rpP0 mRNA in HCC is much higher in HCC than in its
      paraneoplastic tissues. Multiplex RT-PCR assay is an effective, sensitive,
      accurate, and cost-effective diagnostic method of HCC.

PMID- 15991282
TI  - Expression and significance of new inhibitor of apoptosis protein survivin in
      hepatocellular carcinoma.
AB  - AIM: To investigate expression and significance of inhibitor of apoptosis protein
      survivin in hepatocellular carcinoma (HCC). METHODS: The expression of survivin
      and vascular endothelial growth factor (VEGF) was investigated in 38 cases of HCC
      tissues and 38 liver cirrhosis tissues by immunohistochemistry and Western blot.
      The relationship between the expression of survivin and clinicopathological
      factors of HCC was analyzed. RESULTS: Survivin protein was detected in 23 (60.5%)
      of 38 HCCs and 3 (7.9%) of 38 liver cirrhosis tissues. In 23 cases of HCC which
      expressed survivin, the expression of VEGF was positive in 18 cases and slight
      positive or negative in 5 cases. While in 15 cases of HCC which did not express
      survivin, 12 cases did not express or slightly expressed, and 3 cases expressed
      VEGF. In liver cirrhosis tissues, the expression of VEGF was as follows: 24 cases
      were negative, 10 cases were weak positive and 4 cases were strong positive. The
      expression of survivin was coincident with the expression of VEGF in HCC
      (P<0.01). The expression of survivin in HCC had no relationship with the
      patients' age, gender, tumor size and differentiation level of HCC, while it was
      related to the metastasis of HCC. The protein quantitative analysis by Western
      blot also showed that overexpression of survivin in HCC was closely correlated to
      the expression of VEGF (P<0.01). Furthermore, stronger expression of survivin and
      VEGF was also found in patients with metastasis rather than in those with no
      metastasis (P<0.01). CONCLUSION: Survivin plays a pivotal role in the metastasis
      of HCC, and it has some correlation with tumorigenesis. The expression of
      survivin in the primary lesion is very useful as an indicator for metastasis and
      prognosis of HCC. It could become a new target of gene therapy of HCC.

PMID- 15991283
TI  - Activation of transcription factors NF-kappaB and AP-1 and their relations with
      apoptosis associated-proteins in hepatocellular carcinoma.
AB  - AIM: To study the distribution pattern of transcription factors NF-kappaB and AP
      1 and their relations with the expression of apoptosis associated-proteins
      Fas/FasL and ICH-1L/S in human hepatocellular carcinoma (HCC). METHODS: We
      performed in situ hybridization and immunohistochemical techniques for NF-kappaB,
      AP-1, Fas/FasL and ICH-1 in 40 cases of human HCC along with corresponding
      nontumoral tissues and 7 cases of normal liver tissues. RESULTS: Twenty-two (55%)
      and 25 (62.5%) of 40 cases for NF-kappaB and AP-1 were presented for nuclear or
      both nuclear and cytoplastic staining respectively, while less cases were
      presented for only cytoplastic staining for NF-kappaB (18%) and AP-1 (10%) in
      adjacent nontumoral tissues and negative staining in normal liver tissues. There
      was no statistically significant difference of NF-kappaB or AP-1 activation
      between well differentiated tumors and poorly differentiated tumors (P>0.05). NF
      kappaB activity is positively corresponded to AP-1 activation. The expression of
      ICH-1L/S was associated with the activation of NF-kappaB and AP-1 (P<0.05), but
      no significant relationship was found between Fas/FasL and NF-kappaB or AP
      1(P>0.05). CONCLUSION: Activation of both NF-kappaB and AP-1 may be required for
      ICH-1L/S-induced apoptosis in HCC, but not for Fas/FasL-mediated apoptosis. NF
      kappaB and AP-1 may play important roles in the pathogenesis of human HCC.

PMID- 15991284
TI  - Assessment of spiral CT pneumocolon in preoperative colorectal carcinoma.
AB  - AIM: To investigate the value of spiral CT pneumocolon in preoperative colorectal
      carcinoma. METHODS: Spiral CT pneumocolon was performed prior to surgery in 64
      patients with colorectal carcinoma. Spiral CT images were compared to specimens
      from the resected tumor. RESULTS: Spiral CT depicted the tumor in all patients.
      Comparison of spiral CT and histologic results showed that the sensitivity and
      specificity were 95.2%, 40.9% in detection of local invasion, and 75.0%, 90.9% in
      detection of lymph node metastasis. Compared to the Dukes classification, the
      disease was correctly staged as A in 6 of 18 patients, as B in 18 of 23, as C in
      10 of 15, and as D in 7 of 8. Overall, spiral CT correctly staged 64.1% of
      patients. CONCLUSION: Spiral CT pneumocolon may be useful in the preoperative
      assessment of patients with colorectal carcinoma as a means for assisting
      surgical planning.

PMID- 15991285
TI  - Urinary nucleosides as biological markers for patients with colorectal cancer.
AB  - AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were
      evaluated to know the potential as biological markers for patients with
      colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides
      from 52 patients with colorectal cancer, 10 patients with intestinal villous
      adenoma and 60 healthy adults were determined by column switching high
      performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of
      urinary nucleosides (except uridine and guanosine) in the patients with
      colorectal cancer were significantly higher than those in patients with
      intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of
      urinary nucleosides as the data vectors for principal component analysis, 71%
      (37/52) patients with colorectal cancer were correctly classified from healthy
      adults, in which the identification rate was much higher than that of CEA method
      (29%). Only 10% (1/10) of patients with intestinal villous adenoma were
      indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu
      and m1A were positively related with tumor size and Duke's stages of colorectal
      cancer. When monitoring the changes in urinary nucleoside concentrations of
      patients with colorectal cancer associated with surgery, it was found that the
      overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in
      response group and progressive group, respectively. CONCLUSION: These findings
      indicate that urinary nucleosides determined by column switching high performance
      liquid chromatography method may be useful as biological markers for colorectal
      cancer.

PMID- 15991286
TI  - Effects of hepatocyte growth factor/scatter factor on the invasion of colorectal
      cancer cells in vitro.
AB  - AIM: Hepatocyte growth factor (HGF) is a multifunctional growth factor which has
      pleiotrophic biological effects on epithelial cells, such as proliferation,
      motogenesis, invasiveness and morphogenesis. There are few reports about the role
      of HGF played in the colorectal cancer invasion. In the present study, we tried
      to investigate the possible mechanism of HGF involved in the invasion of
      colorectal cancer cells in vitro. METHODS: Matrigel migration assay was used to
      analyze the migrational ability of Caco-2 and Colo320 in vitro. We detected the
      mRNA expressive levels of MMP-2, MMP-9 and their natural inhibitors TIMP-1, TIMP
      2 in Caco-2 cells by reverse-transcription polymerase chain reaction (PCR)
      technique. RESULTS: After 48 h incubation, there were notable differences when we
      compared the migrational numbers of Caco-2 cells in the group of HGF and PD98059
      (the inhibitor of p42/p44MAPK) with the control (104.40+/-4.77 vs 126.80+/-5.40,
      t = 7.17, P = 0.002<0.01; 104.40+/-4.77 vs 82.80+/-4.15, t = 7.96, P =
      0.001<0.01). The deviation between the HGF and PD98059 was significant (P<0.01).
      Compared with controls, MMP-2 and MMP-9 mRNA expressions were up-regulated by HGF
      (0.997+/-0.011 vs 1.207+/-0.003, t = 35.002,P = 0.001<0.01; 0.387+/-0.128 vs
      0.971+/-0.147, t = 106.036, P = 0.0000<0.01, respectively); compared with
      controls, TIMP-1, TIMP-2 mRNA expressions were increased by PD98059 (1.344+/
      0.007 vs 1.905+/-0.049, t = 17.541, P = 0.003<0.01; 1.286+/-0.020 vs 1.887+/
      0.022,t = 24.623, P = 0.002<0.01, respectively). CONCLUSION: HGF promoted Caco-2
      migration mainly by p42/p44MAPK pathway; HGF/SF stimulated the expression of MMP
      2, MMP-9 in Caco-2 and enabled tumoral cells to damage the ECM and reach the
      distant organ and develop metastasis; HGF played the function of promoted
      invasion and promoted-metastasis, in which cellular selection was possible.

PMID- 15991287
TI  - Natural history of major complications in hepatitis C virus-related cirrhosis
      evaluated by per-rectal portal scintigraphy.
AB  - AIM: To examine the correlation between the porto-systemic hypertension evaluated
      by portal shunt index (PSI) and life-threatening complications, including
      hepatocellular carcinoma (HCC), liver failure (Child-Pugh stage progression), and
      esophagogastric varices. METHODS: Two hundred and twelve consecutive subjects
      with HCV-related cirrhosis (LC-C) underwent per-rectal portal scintigraphy. They
      were allocated into three groups according to their PSI: group I, PSI< or =10%;
      group II, 10%<PSI<30%; and group III, 30%< or =PSI. Of these, selected 122 Child
      Pugh stage A (Child A) subjects were included in analysis (a mean follow-up
      period of 5.9+/-5.4 years, range 6 mo-21 years). RESULTS: No significant
      correlation between PSI and cumulative probability of HCC incidence was observed.
      Cumulative probability of Child A to B progression was tended to be higher in
      group III than in group I, and significantly higher in group III than in group II
      (62% vs 34%, 62% vs 37%; P = 0.060, <0.01; respectively). Cumulative probability
      of varices tended to be higher in group III than in group I (31% vs 12%, P =
      0.090). On multivariate analyses, significant correlation between PSI and Child A
      to B progression was observed, and no significant correlation between PSI and HCC
      incidence or varices progression was observed. CONCLUSION: Patients with LC-C of
      Child A will progress to Child B rapidly after their PSI reaches 30% or higher.
      PSI can be used to predict occult progressive porto-systemic shunting and liver
      failure non-invasively. It indicates that PSI may play an important role in
      follow-up of the porto-systemic hypertension gradient for outpatients with LC
      unlike hepatic venous catheterization.

PMID- 15991288
TI  - C-terminal domain of hepatitis C virus core protein is essential for secretion.
AB  - AIM: We have previously demonstrated that hepatitis C virus (HCV) core protein is
      efficiently released into the culture medium in insect cells. The objective of
      this study is to characterize the HCV core secretion in insect cells. METHODS: We
      constructed recombinant baculoviruses expressing various-length of mutant core
      proteins, expressed these proteins in insect cells, and examined core protein
      secretion in insect cells. RESULTS: Only wild type core was efficiently released
      into the culture medium, although the protein expression level of wild type core
      was lower than those of other mutant core proteins. We found that the shorter
      form of the core construct expressed the higher level of protein. However, if
      more than 18 amino acids of the core were truncated at the C-terminus, core
      proteins were no longer secreted into the culture medium. Membrane flotation data
      show that the secreted core proteins are associated with the cellular membrane
      protein, indicating that HCV core is secreted as a membrane complex. CONCLUSION:
      The C-terminal 18 amino acids of HCV core were crucial for core secretion into
      the culture media. Since HCV replication occurs on lipid raft membrane structure,
      these results suggest that HCV may utilize a unique core release mechanism to
      escape immune surveillance, thereby potentially representing the feature of HCV
      morphogenesis.

PMID- 15991289
TI  - Transactivating effect of complete S protein of hepatitis B virus and cloning of
      genes transactivated by complete S protein using suppression subtractive
      hybridization technique.
AB  - AIM: To investigate the transactivating effect of complete S protein of hepatitis
      B virus (HBV) and to construct a subtractive cDNA library of genes transactivated
      by complete S protein of HBV by suppression subtractive hybridization (SSH)
      technique and to clone genes associated with its transactivation activity, and to
      pave the way for elucidating the pathogenesis of hepatitis B virus infection.
      METHODS: pcDNA3.1(-)-complete S containing full-length HBV S gene was constructed
      by insertion of HBV complete S gene into BamH I/Kpn I sites. HepG2 cells were
      cotransfected with pcDNA3.1(-)-complete S and pSV-lacZ. After 48 h, cells were
      collected and detected for the expression of beta-galactosidase (beta-gal).
      Suppression subtractive hybridization and bioinformatics techniques were used.
      The mRNA of HepG2 cells transfected with pcDNA3.1(-)-complete S and pcDNA3.1(-)
      empty vector was isolated, and detected for the expression of complete S protein
      by reverse transcription polymerase chain reaction (RT-PCR) method, and cDNA was
      synthesized. After digestion with restriction enzyme RsaI, cDNA fragments were
      obtained. Tester cDNA was then divided into two groups and ligated to the
      specific adaptors 1 and 2, respectively. After tester cDNA had been hybridized
      with driver cDNA twice and underwent nested PCR twice, amplified cDNA fragments
      were subcloned into pGEM-Teasy vectors to set up the subtractive library.
      Amplification of the library was carried out within E. coli strain DH5alpha. The
      cDNA was sequenced and analyzed in GenBank with BLAST search after polymerase
      chain reaction (PCR) amplification. RESULTS: The complete S mRNA could be
      detected by RT-PCR in HepG2 cells transfected with the pcDNA3.1(-)-complete S.
      The activity of beta-gal in HepG2 cells transfected with the pcDNA3.1(-)-complete
      S was 6.9 times higher than that of control plasmid. The subtractive library of
      genes transactivated by HBV complete S protein was constructed successfully. The
      amplified library contains 86 positive clones. Colony PCR showed that 86 clones
      contained DNA inserts of 200-1 000 bp, respectively. Sequence analysis was
      performed in 35 clones randomly, and the full length sequences were obtained with
      bioinformatics method and searched for homologous DNA sequence from GenBank,
      altogether 33 coding sequences were obtained. These cDNA sequences might be
      target genes transactivated by complete S protein of HBV. Moreover, two unknown
      genes were discovered, full length coding sequences were obtained by
      bioinformatics techniques, one of them was named complete S transactivated
      protein 1 (CSTP1) and registered in GenBank (AY553877). CONCLUSION: The complete
      S gene of HBV has a transactivating effect on SV40 early promoter. A subtractive
      cDNA library of genes transactivated by HBV complete S protein using SSH
      technique has been constructed successfully. The obtained sequences may be target
      genes transactivated by HBV complete S protein among which some genes coding
      proteins are involved in cell cycle regulation, metabolism, immunity, signal
      transduction, cell apoptosis and formation mechanism of hepatic carcinoma.

PMID- 15991290
TI  - Screening of hepatocyte proteins binding to complete S protein of hepatitis B
      virus by yeast-two hybrid system.
AB  - AIM: To investigate the biological function of complete S protein and to look for
      proteins interacting with complete S protein in hepatocytes. METHODS: We
      constructed bait plasmid expressing complete S protein of HBV by cloning the gene
      of complete S protein into pGBKT7, then the recombinant plasmid DNA was
      transformed into yeast AH109 (a type). The transformed yeast AH109 was mated with
      yeast Y187 (alpha type) containing liver cDNA library plasmid in 2XYPDA medium.
      Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp-Leu-His
      Ade) containing X-alpha-gal for selection and screening. After extracting and
      sequencing of plasmids from positive (blue) colonies, we underwent sequence
      analysis by bioinformatics. RESULTS: Nineteen colonies were selected and
      sequenced. Among them, five colonies were Homo sapiens solute carrier family 25,
      member 23 (SLC25A23), one was Homo sapiens calreticulin, one was human serum
      albumin (ALB) gene, one was Homo sapiens metallothionein 2A, two were Homo
      sapiens betaine-homocysteine methyltransferase, three were Homo sapiens Na(+) and
      H(+) coupled amino acid transport system N, one was Homo sapiens CD81 antigen
      (target of anti-proliferative antibody 1) (CD81), three were Homo sapiens
      diazepam binding inhibitor, two colonies were new genes with unknown function.
      CONCLUSION: The yeast-two hybrid system is an effective method for identifying
      hepatocyte proteins interacting with complete S protein of HBV. The complete S
      protein may bind to different proteins i.e., its multiple functions in vivo.

PMID- 15991291
TI  - Prevalence of HFE mutations and relation to serum iron status in patients with
      chronic hepatitis C and patients with nonalcoholic fatty liver disease in Taiwan.
AB  - AIM: To assess the prevalence of the two mutations, C282Y and H63D of HFE gene,
      in healthy subjects, patients with chronic hepatitis C (CHC), and patients with
      nonalcoholic fatty liver disease (NAFLD) in Taiwan and to explore the
      contribution of the HFE mutation on serum iron stores in CHC and NAFLD groups.
      METHODS: We examined C282Y and H63D mutations of HFE gene in 125 healthy
      subjects, 29 patients with CHC, and 33 patients with NAFLD. The serum iron
      markers, including ferritin, iron, and total iron binding capacity (TIBC), were
      assessed in all patients. RESULTS: All of the healthy subjects and patients were
      free from C282Y mutation. The prevalence of H63D heter-ozygosity was 4/125
      (3.20%) in healthy subjects, 2/29 (6.90%) in CHC group, and 1/33 (3.03%) in NAFLD
      group. The healthy subjects showed no significant difference in the prevalence of
      H63D mutation as compared with the CHC or NAFLD group. Increased serum iron store
      was found in 34.48% of CHC patients and 36.36% of NAFLD patients. In three
      patients of H63D heterozygosity, only one CHC patient had increased serum iron
      store. There was no significant difference in the prevalence of HFE mutations
      between patients with increased serum iron store and those without in CHC or
      NAFLD group. CONCLUSION: The HFE mutations may not contribute to iron
      accumulation in the CHC or NAFLD group even when serum iron overload is observed
      in more than one-third of these patients in Taiwan.

PMID- 15991292
TI  - Polymerase chain reaction: a sensitive method for detecting Helicobacter pylori
      infection in bleeding peptic ulcers.
AB  - AIM: To assess the sensitivity and specificity of polymerase chain reaction (PCR)
      in detecting Helicobacter pylori (H pylori) infection in patients with bleeding
      peptic ulcers, and to compare its diagnostic efficacy with other invasive and non
      invasive tests. METHODS: From April to September 2002, H pylori status in 60
      patients who consecutively presented with gastroduodenal ulcer bleeding was
      examined by rapid urease tests (RUT), histology, culture, PCR, serology and urea
      breath tests (UBT). RESULTS: The sensitivity of PCR was significantly higher than
      that of RUT, histology and culture (91% vs 66%, 43% and 37%, respectively; P =
      0.01, <0.001, <0.001, respectively), but similar to that of serology (94%) and
      UBT (94%). Additionally, PCR exhibited a greater specificity than serology (100%
      vs 65%, P<0.01). However, the specificity of PCR did not differ from that of
      other tests. Further analysis revealed significant differences in the
      sensitivities of RUT, culture, histology and PCR between the patients with and
      those without blood in the stomach (P<0.01, P = 0.09, P<0.05, and P<0.05,
      respectively). CONCLUSION: PCR is the most accurate method among the biopsy-based
      tests to detect H pylori infection in patients with bleeding peptic ulcers. Blood
      may reduce the sensitivities of all biopsy-based tests.

PMID- 15991293
TI  - Role of cytokines in promoting immune escape of FasL-expressing human colon
      cancer cells.
AB  - AIM: To investigate the potential role of cytokines in promoting Fas ligand
      (FasL)-expressing colon cancer cells. METHODS: Immunohistochemical SABC method
      was used to observe the expression of Fas receptor and ligand in SW620 colon
      cancer cell line and Jurkat T cells in order to provide the morphological
      evidence for the functions of Fas receptor and ligand. To examine the
      cytotoxicity of effector cells, CytoTox96(r) non-radioactive cytotoxicity assay
      was adopted to measure the lactate dehydrogenase-releasing value after SW620
      cells were co-cultured with Jurkat T lymphocytes. RESULTS: The FasL of colon
      cancer SW620 cells was positive. The positive substances were distributed in the
      cell membrane and cytoplasm. The Fas receptor of colon cancer SW620 cells was
      negative. The Fas receptor and ligand of Jurkat T lymphocytes turned out to be
      positive. The positive substances were distributed in the cell membrane. After
      phytohemagglutinin (PHA)-stimulated Jurkat T lymp-hocytes were co-cultured with
      phorbol 12-myristate 13-acetate (PMA)-plus-ionomycin-stimulated (for 48 h) SW620
      cells or tumor necrosis factor-alpha (TNF-alpha)-stimulated (for 48 h) SW620
      cells or unstimulated SW620 cells for 4 h, the cytotoxicity of SW620 cells to PHA
      stimulated Jurkat cells at effector-to-target ratios of 10:1, 5:1, 2.5:1, and
      1.25:1 was 74.6%, 40.8%, 32.4%, and 10.9% (F = 8.19, P<0.05); or 54.9%, 35.3%,
      22.0%, and 10.3% (F = 11.12, P<0.05); or 14.9%, 10.5%, 6.9%, and 5.8% (F = 3.45,
      P<0.05). After PHA-stimulated Jurkat T lymphocytes were co-cultured with
      unstimulated SW620 cells for 8 h, the cytotoxicity of SW620 cells to PHA
      stimulated Jurkat cells at effector-to-target ratios of 5:1, 2.5:1, and 1.25:1
      from the experiment was 83.9%, 74.1%, and 28.5% (F = 137.04, P<0.05)
      respectively. Non-radioactive cytotoxicity assay showed that the apoptotic rate
      of Jurkat cells remarkably increased with the increase of planting concentration
      of SW620 cells and co-culture time after the SW620 cells were co-cultured with
      the Jurkat T lymphocytes. The cytotoxicity was significantly enhanced by
      PMA+ionomycin or TNF-alpha. CONCLUSION: The FasL expressed in human colon cancer
      cells may be regulated by endogenous factors in the microenvironment of the host
      and facilitate the escape of tumor cells from the host immune system.

PMID- 15991294
TI  - Isoflurane preserves energy balance in isolated hepatocytes during in vitro
      anoxia/reoxygenation.
AB  - AIM: To investigate the protective effect of isoflurane on energy balance in
      isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare
      isoflurane with halothane. METHODS: Hepatocytes freshly isolated from fed rats
      were suspended in Krebs-Henseleit buffer, and incubated in sealed flasks under
      O(2)/CO(2) or N(2)/CO(2) (95%/5%, V/V) for 30 or 60 min, followed by 5 or 10 min
      of reoxygenation, with an added volatile anesthetic or not. ATP, ADP, and
      adenosine monophosphate in hepatocytes were determined by high performance liquid
      chromatography, and energy charge was calculated. RESULTS: During 30 min of
      anoxia, the energy charge and total adenine nucleotide steadily increased with
      the isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration (MAC),
      then decreased from 2 to 3 MAC. In short incubations (30-35 min) at 1 MAC
      isoflurane, energy charge modestly decreased during anoxia, which was partially
      prevented by isoflurane and completely reversed by reoxygenation, and total
      adenine nucleotide did not decrease. In long incubations (60-70 min), both energy
      charge and total adenine nucleotide greatly decreased during anoxia, with partial
      and no reversal by reoxygenation, respectively. Isoflurane partly prevented
      decreases in both energy charge and total adenine nucleotide during anoxia and
      reoxygenation. In addition, 1 MAC isoflurane obviously increased ATP/ADP, which
      could not be changed by 1 MAC halothane. CONCLUSION: Isoflurane partially
      protects isolated hepatocytes against decreases in both energy charge and total
      adenine nucleotide during short (reversible) or long (irreversible) anoxia.

PMID- 15991295
TI  - Clinical evidence of growth hormone for patients undergoing abdominal surgery:
      meta-analysis of randomized controlled trials.
AB  - AIM: To assess the effectiveness and safety of perioperative growth hormone (GH)
      in patients undergoing abdominal surgery. METHODS: We searched the following
      electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register,
      Chinese Bio-medicine Database. The search was undertaken in February 2003. No
      language restrictions were applied. Randomized controlled trials (RCT) comparing
      GH with placebo in patients undergoing abdominal surgery were extracted and
      evaluated. Methodological quality was evaluated using the Jadad scale. RESULTS:
      Eighteen trials involving 646 patients were included. The combined results showed
      that GH had a positive effect on improving postoperative nitrogen balance
      (standardized mean difference (SMD) = 3.37, 95%CI (2.46, 4.27), P<0.00001), and
      decreasing the length of hospital stay (weighted mean difference (WMD) = -2.07,
      95%CI (-3.03, -1.11), P = 0.00002), and reducing the duration of postoperative
      fatigue syndrome (SMD = -1.83, 95%CI (-2.37, -1.30), P<0.00001), but it could
      increase blood glucose levels (WMD = 0.91, 95%CI (0.56, 1.25), P<0.00001).
      CONCLUSION: GH for patients undergoing abdominal surgery is effective and safe,
      if blood glucose can be controlled well. Further trials are required with a
      sufficient size to account for clinical heterogeneity and to measure other
      important outcomes such as infection, morbidity, mortality, fluid retention,
      immunomodulatory effects, and tumor recurrence.

PMID- 15991296
TI  - Autofluorescence excitation-emission matrices for diagnosis of colonic cancer.
AB  - AIM: To investigate the autofluorescence spectroscopic differences in normal and
      adenomatous colonic tissues and to determine the optimal excitation wavelengths
      for subsequent study and clinical application. METHODS: Normal and adenomatous
      colonic tissues were obtained from patients during surgery. A FL/FS920 combined
      TCSPC spectrofluorimeter and a lifetime spectrometer system were used for
      fluorescence measurement. Fluorescence excitation wavelengths varying from 260 to
      540 nm were used to induce the autofluorescence spectra, and the corresponding
      emission spectra were recorded from a range starting 20 nm above the excitation
      wavelength and extending to 800 nm. Emission spectra were assembled into a three
      dimensional fluorescence spectroscopy and an excitation-emission matrix (EEM) to
      exploit endogenous fluorophores and diagnostic information. Then emission spectra
      of normal and adenomatous colonic tissues at certain excitation wavelengths were
      compared to determine the optimal excitation wavelengths for diagnosis of colonic
      cancer. RESULTS: When compared to normal tissues, low NAD(P)H and FAD, but high
      amino acids and endogenous phorphyrins of protoporphyrin IX characterized the
      high-grade malignant colonic tissues. The optimal excitation wavelengths for
      diagnosis of colonic cancer were about 340, 380, 460, and 540 nm. CONCLUSION:
      Significant differences in autofluorescence peaks and its intensities can be
      observed in normal and adenomatous colonic tissues. Autofluorescence EEMs are
      able to identify colonic tissues.

PMID- 15991297
TI  - Application of dietary fiber in clinical enteral nutrition: a meta-analysis of
      randomized controlled trials.
AB  - AIM: To evaluate the effects of dietary fiber (DF) as a part of enteral nutrition
      (EN) formula on diarrhea, infection, and length of hospital stay. METHODS:
      Following electronic databases were searched for randomized controlled trials
      about DF: Chinese Biomedicine Database (CBM), MEDLINE, EMBASE and Cochrane
      Controlled Trials Register. RevMan 4.1 was used for statistical analysis.
      RESULTS: Seven randomized controlled trials with 400 patients were included. The
      supplement of DF in EN was compared with standard enteral formula in five trials.
      Combined analysis did not show a significant reduction in occurrence of diarrhea,
      but there were valuable results for non-critically ill patients. Combined
      analysis of two trials observing the infection also did not show any valid
      evidence that DF could decrease the infection rate, though the length of hospital
      stay was reduced significantly. CONCLUSION: Based on the current eligible
      randomized controlled trials, there is no evidence that the value of DF in the
      diarrhea can be proved. Though length of hospital stay was shortened by the use
      of DF, there is no available evidence in preventing infection by DF. Further
      studies are needed for evaluating the value of DF in EN.

PMID- 15991298
TI  - Personal experience with the procurement of 32 liver allografts.
AB  - AIM: To introduce the American Pittsburgh's method of rapid liver procurement
      under the condition of brain death and factors influencing the quality of donor
      liver. METHODS: To analyze 32 cases of allograft liver procurement
      retrospectively and observe the clinical outcome of orthotopic liver
      transplantation. RESULTS: Average age of donors was 38.24+/-12.78 years, with a
      male:female ratio of 23:9. The causes of brain death included 21 cases of trauma
      (65.63%) and nine cases of cerebrovascular accident (28.13%). Fourteen grafts
      (43.75%) had hepatic arterial anomalies, seven cases only right hepatic arterial
      anomalies (21.88%), five cases only left hepatic arterial anomalies (15.63%) and
      two cases of both right and left hepatic arterial anomalies (6.25%) among them.
      Eight cases (57.14%) of hepatic arterial anomalies required arterial
      reconstruction prior to transplantation. Of the 32 grafts evaluated for early
      function, 27 (84.38%) functioned well, whereas three (9.38%) functioned poorly
      and two (6.25%) failed to function at all. Only one recipient died after
      transplantation and thirty-one recipients recovered. Four recipients needed
      retransplantation. The variables associated with less than optimal function of
      the graft consisted of donor age (35.6+/-12.9 years vs 54.1+/-4.3 years, P<0.05),
      duration of donor's stay in the intensive care unit (ICU) (3.5+/-2.4 d vs 7.4+/
      2.1 d, P<0.005), abnormal graft appearance (19.0% vs 100%, P<0.05), and such
      recipient problems as vascular thromboses during or immediately following
      transplantation (89.3% vs 50.0%, P<0.005). CONCLUSION: During liver procurement,
      complete heparization, perfusion in situ with localized low temperature and
      standard technique procedures are the basis ensuring the quality of the graft.
      The hepatic arterial anomalies should be taken care of to avoid injury. The donor
      age, duration of donor's staying in ICU, abnormal graft appearance and recipient
      problem are important factors influencing the quality of the liver graft.

PMID- 15991299
TI  - 5-Fluorouracil concentration in blood, liver and tumor tissues and apoptosis of
      tumor cells after preoperative oral 5'-deoxy-5-fluorouridine in patients with
      hepatocellular carcinoma.
AB  - AIM: To study the levels of 5-fluorouracail (5-FU) in plasma, liver and tumor in
      patients with hepatocellular carcinoma after oral administration of 5'-deoxy-5
      fluorouridine (5'-DFUR). METHODS: Thirty-nine patients with hepatocellular
      carcinoma were treated with oral 5'-DFUR for more than 4 d before operation. The
      contents of 5-FU in plasma, liver and tumor were measured by high performance
      liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in
      situ TUNEL after resection of tumor. RESULTS: The concentrations of 5-FU were 1.1
      mug/mL, 5.6, 5.9, and 10.5 mug/g in plasma, the liver tissue, the center of tumor
      and the periphery of tumor, respectively. 5-FU concentration was significantly
      higher in the periphery of tumor than that in the liver tissue and the center of
      tumor (10.5+/-1.6 mug/g vs 5.6+/-0.8 mug/g, t = 21.38, P<0.05; 10.5+/-1.6 mug/g
      vs 5.9+/-0.9 mug/g, t = 20.07, P<0.05). 5-FU level was significantly lower in
      plasma than that in the liver and the tumor (1.1+/-0.3 mug/mL vs 5.6+/-0.8 mug/g,
      t = 19.63, P<0.05; 1.1+/-0.3 mug/mL vs 10.5+/-1.6 mug/g, t = 41.01, P<0.05).
      Apoptosis of tumor cells was significantly increased after oral 5'-DFUR compared
      to the control group without 5'-DFUR treatment. CONCLUSION: There is a higher
      concentration of 5-FU distributed in the tumor compared with liver tissue and
      apoptosis of tumor cells is increased following oral 5'-DFUR compared with the
      control group. The results indicate that 5'-DFUR is hopeful as neo-adjuvant
      chemotherapy to prevent recurrence after resection of hepatocellular carcinoma.

PMID- 15991300
TI  - Prognostic value of KIT mutation in gastrointestinal stromal tumors.
AB  - AIM: To examine the prevalence and prognostic significance of C-kit gene mutation
      and analysis the correlation of C-kit gene mutation and the clinicalpathologic
      parameters of GISTs. METHODS: Eighty-two GISTs were studied for the mutation of C
      kit gene by PCR-SSCP, DNA sequence. Statistical comparison were used to analysis
      the correlation of C-kit gene mutation and clinicalpathology, clinical behavior,
      recurrence. RESULTS: (1) Mutation-positive and mutation-negative GISTs were 34
      and 48,respectively; (2) Among these patients with C-kit mutation remained a
      significantly poor prognosis associated with 59% 3-year survival compared to
      those whose tumors did not; (3) Tumor size, PCNA index, mitotic cell number,
      presence of necrosis, microscopic invasion to adjacent tissues, recurrence and
      distant metastasis among mutation-positive and mutation-negative GISTs were
      significantly different. CONCLUSION: C-kit mutation is a undoubtedly pivotal
      event in GIST and may be associated with poor prognosis. Evaluation of C-kit gene
      mutation may have both prognosis and therapeutic significances.

PMID- 15991301
TI  - Somatostatin receptor subtype 2-mediated scintigraphy and localization using
      (99m)Tc-HYNIC-Tyr(3)-octreotide in human hepatocellular carcinoma-bearing nude
      mice.
AB  - AIM: To investigate the uptake of (99m)Tc-HYNIC-Tyr(3)-octreotide ((99m)Tc-HYNIC
      TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable
      diagnosis in hepatic carcinoma. METHODS: The expression of somatostatin receptor
      2 (SSTR2) messenger RNA (mRNA) in human HCC cell line HepG(2) was examined by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of (99m)Tc-HYNIC
      TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000
      nuclear medicine analysis system was used to calculate the ratio of (99m)Tc
      uptake between tumor tissue and vital organs. RESULTS: We demonstrated the
      expression of SSTR2 mRNA in human HCC cell line HepG(2) by RT-PCR. The size of
      the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2
      mRNA. Scintigraphy proved that (99m)Tc-HYNIC-TOC was uptaken in the tumor tissue,
      liver and kidney of the tumor-bearing mice. CONCLUSION: Based on expression of
      the SSTR2 mRNA in human HCC, (99m)Tc-HYNIC-TOC can markedly bind with and be
      uptaken by human HCC tissues as compared with normal liver tissue. The
      significant retention of radionuclide in kidney and bladder is probably related
      to non-specific peptide uptake in the tubulus cells of kidney and possibly due to
      excretion by kidney. Our results show that localizable diagnosis and targeting
      radiotherapy with radionuclide-labeled somatostatin analog for HCC are of great
      value to be further studied.

PMID- 15991302
TI  - Effects of He-Ne laser irradiation on chronic atrophic gastritis in rats.
AB  - AIM: To study the effects of He-Ne laser irradiation on experimental chronic
      atrophic gastritis (CAG) in rats. METHODS: Sixty-three male adult Wistar rats
      were randomly divided into five groups including normal control group, model
      control group and three different dosages He-Ne laser groups. The chronic
      atrophic gastritis (CAG) model in rats was made by pouring medicine which was a
      kind of mixed liquor including 2% sodium salicylate and 30% alcohol down the
      throat for 8 wk to stimulate rat gastric mucosa, combining with irregular fasting
      and compulsive sporting as pathogenic factors; 3.36, 4.80, and 6.24 J/cm(2) doses
      of He-Ne laser were used, respectively for three different treatment groups, once
      a day for 20 d. The pH value of diluted gastric acid was determined by
      acidimeter, the histopathological changes such as the inflammatory degrees in
      gastric mucosa, the morphology and structure of parietal cells were observed, and
      the thickness of mucosa was measured by micrometer under optical microscope.
      RESULTS: In model control group, the secretion of gastric acid was little,
      pathologic morphological changes in gastric mucosa such as thinner mucous,
      atrophic glands, notable inflammatory infiltration were found. After 3.36 J/cm(2)
      dose of He-Ne laser treatment for 20 d, the secretion of gastric acid was
      increased (P<0.05), the thickness of gastric mucosa was significantly thicker
      than that in model control group (P<0.01), the gastric mucosal inflammation cells
      were decreased (P<0.05). Morphology, structure and volume of the parietal cells
      all recuperated or were closed to normal. CONCLUSION: 3.36 J/cm(2) dose of He-Ne
      laser has a significant effect on CAG in rats.

PMID- 15991303
TI  - Expression of interferon-alpha/beta receptor protein in liver of patients with
      hepatitis C virus-related chronic liver disease.
AB  - AIM: To study the expression of interferon-alpha/beta (IFN-alpha/beta) receptor
      protein in liver of patients with hepatitis C virus (HCV)-related chronic liver
      disease and its clinical significance. METHODS: A total of 181 patients with HCV
      related chronic liver disease included 56 with HCV-related liver cirrhosis (LC)
      and 125 with chronic hepatitis C (CHC). CHC patients were treated with five
      megaunits of interferon-?1b six times weekly for the first 2 weeks and then every
      other day for 22 wk. The patients were divided into interferon (IFN) treatment
      responsive and non-responsive groups, but 36 patients lost follow-up shortly
      after receiving the treatment. The expression of IFN-alpha/beta receptor (IFN
      alpha/betaR) protein in liver of all patients was determined with
      immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver
      disease, the expression of IFN-alpha/betaR protein in liver cell membrane was
      stronger than that in cytoplasm and more obvious in the surroundings of portal
      vein than in the surroundings of central vein. Moreover, it was poorly
      distributed in hepatic lobules. The weak positive, positive and strong positive
      expression of IFN-alpha/betaR were 40% (50/125), 28% (35/125), 32% (40/125),
      respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56),
      respectively in LC group. The positive and strong positive rates were higher in
      CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8%
      (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong
      positive expression. In the non-responsive group, 71.7% (38/53) showed weak
      positive expression; 28.3% (15/53) showed positive or strong positive expression.
      The expression of IFN-alpha/betaR protein in liver was more obvious in IFN
      treatment responsive group than in non-responsive group. CONCLUSION: Expression
      of IFN-alpha/betaR protein in liver of patients with HCV-related chronic liver
      disease is likely involved in the response to IFN treatment.

PMID- 15991305
TI  - Gene symbol: PANK2. Disease: Pantothenate kinase associated neurodegeneration
      (PKAN).

PMID- 15991304
TI  - Surgical treatment of hepatocellular carcinoma with bile duct tumor thrombi.
AB  - AIM: To study the surgical treatment effect and outcome of hepatocellular
      carcinoma (HCC) with bile duct tumor thrombi (BDTT). METHODS: Fifty-three
      consecutive HCC patients with BDTT admitted in our department from July 1984 to
      December 2002 were reviewed retrospectively. The clinical data, diagnostic
      methods, surgical procedures and outcome of these patients were collected and
      analyzed. RESULTS: One patient rejected surgical treatment, 6 cases underwent
      percutaneous transhepatic cholangial drainage (PTCD) for unresectable primary
      disease, and the other 46 cases underwent surgical operation. The postoperative
      mortality was 17.6%, and the morbidity was 32.6%. Serum total bilirubin levels of
      these patients with obstructive jaundice decreased gradually after surgery. The
      survival time of six cases who underwent PTCD ranged from 2 to 7 mo (median
      survival of 3.7 mo). The survival time of the patients who received surgery was
      as follows: 2 mo for one patient who underwent laparotomy, 5-46 mo (median
      survival of 23.5 mo, which was the longest survival in comparison with patients
      who underwent other procedures, P = 0.0024) for 17 cases who underwent
      hepatectomy, 5-17 mo (median survival of 10.0 mo) for 5 cases who underwent HACE,
      3-9 mo (median survival of 6.1 mo) for 11 cases who underwent simple thrombectomy
      and biliary drainage, and 3-8 mo (median survival of 4.3 mo) for four cases who
      underwent simple biliary drainage. CONCLUSION: Jaundice caused by BDTT in HCC
      patients is not a contraindication for surgery. Only curative resection can
      result in long-term survival. Early diagnosis and surgical treatment are the key
      points to prolong the survival of patients.

PMID- 15991306
TI  - Gene symbol: MLH1. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15991307
TI  - Gene symbol: MSH2. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15991308
TI  - Gene symbol: MSH2. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15991309
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991310
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991311
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991312
TI  - Gene symbol: HMBS. Disease: Porphyria, acute intermittent.

PMID- 15991313
TI  - Gene symbol: IPF1. Disease: MODY 4.

PMID- 15991314
TI  - Gene symbol: MSH2. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15991315
TI  - Gene symbol: MSH2. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15991316
TI  - Gene symbol: MSH2. Disease: Hereditary nonpolyposis colorectal cancer.

PMID- 15991317
TI  - Gene symbol: CYP17A1. Disease: Steroid 17-alpha-hydrolylase deficiency.

PMID- 15991318
TI  - Gene symbol: WAS. Disease: Wiskott-Aldrich syndrome.

PMID- 15991319
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991320
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991321
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991322
TI  - Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.

PMID- 15991323
TI  - Gene symbol: SLC40A1. Disease: Primary iron overload.

PMID- 15991324
TI  - Gene symbol: SLC3A1. Disease: Cystinuria.

PMID- 15991325
TI  - Gene symbol: AIPL1. Disease: LCA4.

PMID- 15991326
TI  - Gene symbol: GLB1. Disease: GM1 gangliosidosis infantile.

PMID- 15991327
TI  - Gene symbol: GLB1. Disease: GM1 gangliosidosis infantile.

PMID- 15991328
TI  - Gene symbol: SLC3A1. Disease: Cystinuria.

PMID- 15991329
TI  - Gene symbol: F2. Disease: Hypoprothrombinemia.

PMID- 15991330
TI  - Gene symbol: HMBS. Disease: Porphyria, acute intermittent.

PMID- 15991331
TI  - Gene symbol: CLN3. Disease: Juvenile neuronal ceroid lipofuscinosis (Batten
      disease).

PMID- 15991332
TI  - Gene symbol: TYR. Disease: Albinism, oculocutaneous 1.

PMID- 15991333
TI  - Gene symbol: TYR. Disease: Albinism, oculocutaneous 1.

PMID- 15991334
TI  - Gene symbol: TYR. Disease: Albinism, oculocutaneous 1.

PMID- 15991335
TI  - Gene symbol: PANK2. Disease: Pantothenate kinase associated neurodegeneration
      (PKAN).

PMID- 15991336
TI  - Gene symbol: CTSC. Disease: Papillon-Lefevre syndrome.

PMID- 15991337
TI  - MEDock: a web server for efficient prediction of ligand binding sites based on a
      novel optimization algorithm.
AB  - The prediction of ligand binding sites is an essential part of the drug discovery
      process. Knowing the location of binding sites greatly facilitates the search for
      hits, the lead optimization process, the design of site-directed mutagenesis
      experiments and the hunt for structural features that influence the selectivity
      of binding in order to minimize the drug's adverse effects. However, docking is
      still the rate-limiting step for such predictions; consequently, much more
      efficient algorithms are required. In this article, the design of the MEDock web
      server is described. The goal of this sever is to provide an efficient utility
      for predicting ligand binding sites. The MEDock web server incorporates a global
      search strategy that exploits the maximum entropy property of the Gaussian
      probability distribution in the context of information theory. As a result of the
      global search strategy, the optimization algorithm incorporated in MEDock is
      significantly superior when dealing with very rugged energy landscapes, which
      usually have insurmountable barriers. This article describes four different
      benchmark cases that span a diverse set of different types of ligand binding
      interactions. These benchmarks were compared with the use of the Lamarckian
      genetic algorithm (LGA), which is the major workhorse of the well-known AutoDock
      program. These results demonstrate that MEDock consistently converged to the
      correct binding modes with significantly smaller numbers of energy evaluations
      than the LGA required. When judged by a threshold of the number of energy
      evaluations consumed in the docking simulation, MEDock also greatly elevates the
      rate of accurate predictions for all benchmark cases. MEDock is available at
      http://medock.csie.ntu.edu.tw/ and http://bioinfo.mc.ntu.edu.tw/medock/.

PMID- 15991338
TI  - SVC: structured visualization of evolutionary sequence conservation.
AB  - We have developed a web application for the detailed analysis and visualization
      of evolutionary sequence conservation in complex vertebrate genes. Given a pair
      of orthologous genes, the protein-coding sequences are aligned. When these
      sequences are mapped back onto their encoding exons in the genomes, a scaffold of
      the conserved gene structure naturally emerges. Sequence similarity between exons
      and introns is analysed and embedded into the gene structure scaffold. The
      visualization on the SVC server provides detailed information about
      evolutionarily conserved features of these genes. It further allows concise
      representation of complex splice patterns in the context of evolutionary
      conservation. A particular application of our tool arises from the fact that
      around mRNA editing sites both exonic and intronic sequences are highly
      conserved. This aids in delineation of these sites. SVC is available at
      http://svc.molgen.mpg.de.

PMID- 15991339
TI  - PRISM: protein interactions by structural matching.
AB  - Prism (http://gordion.hpc.eng.ku.edu.tr/prism) is a website for protein interface
      analysis and prediction of putative protein-protein interactions. It is composed
      of a database holding protein interface structures derived from the Protein Data
      Bank (PDB). The server also includes summary information about related proteins
      and an interactive protein interface viewer. A list of putative protein-protein
      interactions obtained by running our prediction algorithm can also be accessed.
      These results are applied to a set of protein structures obtained from the PDB at
      the time of algorithm execution (January 2004). Users can browse through the non
      redundant dataset of representative interfaces on which the prediction algorithm
      depends, retrieve the list of similar structures to these interfaces or see the
      results of interaction predictions for a particular protein. Another service
      provided is interactive prediction. This is done by running the algorithm for
      user input structures.

PMID- 15991340
TI  - Abstracts of the 50th Annual Meeting of the Health Physics Society. Spokane,
      Washington, USA, 10-14 July 2005.

PMID- 15991342
TI  - Abstracts of the Canadian Foundation for Dietetic Research Meeting, May 28, 2005.

PMID- 15991341
TI  - Abstracts of the 82nd Annual Meeting of the Physiological Society of Japan. May
      18-20, 2005, Sendai, Japan.

PMID- 15991343
TI  - Abstracts of the 6th Central European Symposium on Pharmaceutical Technology and
      Biotechnology. May 25-27, 2005, Siofok, Hungary.

PMID- 15991344
TI  - ESGAR 2005. Abstracts of the 16th annual meeting and postgraduate course of the
      European Society of Gastrointestinal and Abdominal Radiology. May 28-31,
      Florence, Italy.

PMID- 15991345
TI  - Early management of suspected bacterial meningitis and meningococcal septicaemia
      in immunocompetent adults--second edition.
AB  - Bacterial meningitis and meningococcal septicaemia continue to cause death and
      disability in adults. This updated algorithm focuses on minimising delays in
      diagnosis and administration of antibiotics, appropriate use of monitoring,
      investigations, critical care facilities and management of complications, taking
      into account emerging evidence and the latest national recommendations.

PMID- 15991346
TI  - 2005 Epidemiology without Borders. Abstracts of a joint meeting of the Society
      for Epidemiologic Research and Canadian Society of Epidemiology and
      Biostatistics. Toronto, Canada, June 27-30, 2005.

PMID- 15991347
TI  - Abstracts of the XVIIth Conference on Postural and Gait Research. Marseille,
      France, May 29-June 2, 2005.

PMID- 15991348
TI  - Abstracts of the 16th International Congress on Parkinson's Disease and Related
      Disorders. Berlin, Germany, June 5-9, 2005.

PMID- 15991350
TI  - Role of state EMS medical director.

PMID- 15991351
TI  - Emergency contraception for women at risk of unintended and preventable
      pregnancy.

PMID- 15991349
TI  - Methodology of laboratory measurements in prospective studies on gene-environment
      interactions: the experience of GenAir.
AB  - Several large prospective investigations are under way or are planned in
      different parts of the world, aiming at the investigation of gene-environment
      interactions for chronic diseases. Technical, practical and ethical issues are
      raised by such large investigations. Here we describe how such issues were
      approached within a case-control study nested in EPIC, a large European cohort,
      and the kind of validation studies that have been set up. The GenAir
      investigation aimed at measuring the effects of air pollution and environmental
      tobacco smoke on human health in EPIC with a nested design and with biological
      measures. Validation studies included (a) comparisons between cotinine
      measurements, hemoglobin adducts and questionnaire data; (b) an analysis of the
      determinants of DNA adduct concentration; (c) comparison among different
      genotyping methods; (d) an analysis of the determinants of plasma DNA amounts. We
      also describe how the ethical issues were dealt with in our investigation.

PMID- 15991352
TI  - Procedural sedation in the emergency department.

PMID- 15991353
TI  - Assault weapon ban.

PMID- 15991354
TI  - Caring for emergency department "boarders".

PMID- 15991355
TI  - Compensation arrangements for emergency physicians.

PMID- 15991356
TI  - Aspirin in the prevention of cardiovascular disease in women.

PMID- 15991357
TI  - Cardiac revascularization in specialty and general hospitals.

PMID- 15991358
TI  - Cardiac revascularization in specialty and general hospitals.

PMID- 15991359
TI  - Polycystic ovary syndrome.

PMID- 15991361
TI  - Proceedings of the 3rd Genoa Meeting on Hypertension, Diabetes, and Renal
      Diseases. Genoa, Italy, February 26-28, 2004.

PMID- 15991360
TI  - Polycystic ovary syndrome.

PMID- 15991362
TI  - A plague of autoantibodies.

PMID- 15991364
TI  - HIV/AIDS and human rights: we've only just begun.
AB  - Public health and human rights often used to be seen as incompatible frameworks
      for action. HIV/AIDS was supposed to break that mould and be the epidemic where
      respecting human rights would be the most effective way to achieve the public
      health goal of conquering the epidemic. In this article, Joanne Csete suggests
      that while in theory everybody buys into the effectiveness of rights-based
      approaches to HIV/AIDS, the practice leaves much to be desired. The author
      describes the human rights framework that is the foundation for a more effective
      response to HIV/AIDS and stresses the urgency of paying more than lip service to
      the need to put human rights at the centre of the fight against HIV/AIDS in
      Canada and beyond.

PMID- 15991365
TI  - AIDS, drugs and terrorism: do I have your attention?

PMID- 15991366
TI  - A long way from there to here: human rights approaches to HIV/AIDS in a local
      setting.
AB  - Although global and national strategies to promote a human rights-based approach
      to HIV/AIDS have been in place for many years, these strategies appear to have
      had little impact at the local level, where human rights violations are
      commonplace. In this article, Peris Jones and Farhana Zuberi summarize findings
      from a recently completed research project, the Tswelopele study, in South
      Africa. The study documented human rights violations in three areas: privacy and
      disclosure; informed consent and HIV testing; and access to health-care services.
      The article describes these violations and explores why discrimination still
      occurs at the local level. The authors conclude that remedial action is required,
      targeting the persons and institutions that shape attitudes and beliefs,
      including churches, workplaces, schools, and the media; and that this action
      needs to be complemented by wider public education, activism at hospitals and in
      the courts and, more generally, fulfillment of socio-economic rights.

PMID- 15991363
TI  - Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1
      polarization by preventing Notch upregulation of Tbx21.
AB  - Notch receptors are processed by gamma-secretase acting in synergy with T cell
      receptor signaling to sustain peripheral T cell activation. Activated CD4+ T
      cells differentiate into T helper type 1 (TH1) or TH2 subsets. Molecular cues
      directing TH1 differentiation include expression of the TH1-specific
      transcription factor T-bet, encoded by Tbx21. However, the regulation of Tbx21
      remains incompletely defined. Here we report that Notch1 can directly regulate
      Tbx21 through complexes formed on the Tbx21 promoter. In vitro, gamma-secretase
      inhibitors extinguished expression of Notch, interferon-gamma and Tbx21 in TH1
      polarized CD4+ cells, whereas ectopic expression of activated Notch1 restored
      Tbx21 transcription. In vivo, administration of gamma-secretase inhibitors
      substantially impeded TH1-mediated disease progression in the mouse experimental
      autoimmune encephalomyelitis model of multiple sclerosis. Thus, using gamma
      secretase inhibitors to modulate Notch signaling may prove beneficial in treating
      TH1-mediated autoimmunity.

PMID- 15991367
TI  - Protection against discrimination based on HIV/AIDS status in Canada: the legal
      framework.
AB  - Respecting, protecting ,and fulfilling the human rights of people living with,
      and vulnerable to, HIV/AIDS has been recognized as an essential element of
      ethical and effective responses to the epidemic. Human rights law provides one
      critical tool for implementing a human rights-based approach to HIV/AIDS. Freedom
      from discrimination is a foundational human rights principle, and is a touchstone
      of both international and domestic human rights law. This article examines the
      ways in which Canadian law currently protects people against discrimination based
      on HIV/AIDS status. The article also reviews the equality rights provision of the
      Canadian Charter of Rights and Freedoms; federal, provincial, and territorial
      anti-discrimination statutes and policies; and some of the key cases that have
      applied and developed these legislative protections. Finally, the article looks
      at the issue of remedies for discrimination under Canadian law. (Other forms of
      discrimination relevant to people living with HIV/AIDS--specifically,
      discrimination based on grounds relevant to people from groups disproportionately
      affected by HIV/AIDS-related stigma--will be analyzed in similar detail in a
      future issue of the Review.)

PMID- 15991368
TI  - Legal Network launches Plan of Action on HIV/AIDS-related stigma and
      discrimination.
AB  - On 26 January 2005, the Canadian HIV/AIDS Legal Network launched A Plan of Action
      for Canada to reduce HIV/AIDS-related stigma and discrimination. The kick-off
      included a national press conference on Parliament Hill, and local press
      conferences by six community-based organizations across Canada.

PMID- 15991369
TI  - Alberta review panel recommendations threaten privacy of personal health
      information.
AB  - In a report released in October 2004, the Alberta Select Special Health
      Information Act Review Committee has recommended increasing the situations under
      which custodians of health information can release such information. If these
      recommendations become law, people living with HIV/AIDS would have less control
      over the disclosure of their health information, including their HIV status.

PMID- 15991370
TI  - Medical marijuana developments.

PMID- 15991371
TI  - New Brunswick: new sex education curriculum stirs debate.
AB  - Controversy has surrounded the sex education component of the New Brunswick
      Department of Education's new health curriculum for grades six, seven, and eight.

PMID- 15991372
TI  - Standing Committee on Justice re-establishes Subcommittee on Solicitation Laws.
AB  - On 24 November 2004, the House of Commons Standing Committee on Justice, Human
      Rights, Public Safety and Emergency Preparedness established a Subcommittee on
      Solicitation Laws to review the Criminal Code provisions relating to
      prostitution. A previous subcommittee with a similar mandate was disbanded when
      Parliament was prorogued in 2003.

PMID- 15991374
TI  - Another call for needle exchange programs in prisons.

PMID- 15991373
TI  - Quebec activists draws attention to lypodistrophy.

PMID- 15991375
TI  - Breaking new ground on HIV/AIDS and human rights in China.
AB  - A ground-breaking meeting of HIV/AIDS NGOs and community-based activists in
      China, focusing largely on legal and human rights issues related to HIV/AIDS, was
      held in Shanghai in December 2004. This was one of the first meetings in China
      where people living with HIV/AIDS from diverse communities were able to share
      openly their experiences and to discuss in detail the human rights, legal, and
      policy measures that are needed to protect people living with HIV/AIDS in China
      and to enable civil society organizations to contribute to China's fight against
      HIV/AIDS.

PMID- 15991376
TI  - Caribbean: birth of a regional network responding to HIV/AIDS and vulnerability.
AB  - In December 2004, representatives from 30 Caribbean NGOs met in Kingston, Jamaica
      to form a regional network of organizations working with populations most
      vulnerable to HIV/AIDS--the Caribbean Vulnerable Communities (CVC) Network. In
      this article, two Caribbean researchers and activists situate this vulnerability
      and the civil society response in their specific socio-historical context.

PMID- 15991377
TI  - Jamaica: report documents homophobia and violence.
AB  - In November 2004, Human Rights Watch (HRW) released a report documenting
      widespread violence and discrimination against people living with, and at high
      risk of, HIV/AIDS in Jamaica. The report alleges police use Jamaica's Victorian
      era sodomy laws, which criminalize consensual sex between adult men, as a basis
      to harass and persecute people suspected of homosexual conduct and peer educators
      who provide HIV/AIDS information and condoms to them.

PMID- 15991378
TI  - Hungary: segregation of HIV-positive prisoners breaches national and
      international standards.
AB  - In October 2004 the Hungarian Civil Liberties Union (HCLU) filed a petition to
      the Hungarian Constitutional Court concerning segregation of HIV-positive inmates
      in correctional facilities in Hungary.

PMID- 15991379
TI  - Ukrainian survey of PLHA rights reveals widespread abuses.
AB  - A survey conducted in 2004 by the All-Ukrainian Network of People Living with HIV
      found that HIV-related rights violations are widespread in Ukrainian society, and
      that many people living with HIV/AIDS (PLHA) are ignorant of the provisions of
      HIV/AIDS-related legislation.

PMID- 15991380
TI  - Nepal: legal system HIV/AIDS audit conducted.
AB  - An HIV/AIDS audit of the legal system of Nepal, carried out in 2004 by the Forum
      for Women, Law and Development (FWLD), found that Nepal has poor public health
      legislation, but good regulation of health-care professionals and research.

PMID- 15991381
TI  - Mexico: general Recommendation issued on school-based discrimination against HIV
      positive children.
AB  - In September 2004, Mexico's National Human Rights Commission (NHRC) issued a
      General Recommendation responding to various discriminatory practices by federal
      and local education officials against children living with HIV/AIDS. The
      Recommendation reflects the general guidance provided by the Committee on the
      Rights of the Child in its 2003 General Comments on HIV/AIDS and the Rights of
      the Child, and Adolescent Health.

PMID- 15991382
TI  - Botswana: National Policy on HIV/AIDS and the World of Work.

PMID- 15991383
TI  - Nigeria: HIV-positive journalism student reinstated after mobilization and threat
      of legal action.

PMID- 15991384
TI  - Nigeria: public lecture series highlights deficiencies in national law and
      policy.

PMID- 15991385
TI  - Kenya: law students assist with HIV/AIDS legal clinics.

PMID- 15991386
TI  - Ukraine: advocacy workshops support PLWA rights and advance HIV prevention.

PMID- 15991387
TI  - Canadian AIDS Society granted intervener status in blood donor case.
AB  - The Canadian AIDS Society (CAS) was recently denied leave to intervene as an
      added party in a case related to screening criteria for blood donations. The
      court did however grant CAS the right to intervene as a friend of the court,
      which is a more restricted status.

PMID- 15991388
TI  - Criminal law and HIV transmission/exposure: two new cases.

PMID- 15991389
TI  - Court takes HIV status into account in robbery sentencing.

PMID- 15991390
TI  - Colombia: Constitutional Court grants interim order reinstating HIV-positive
      woman in her job.
AB  - In late 2004 the Constitutional Court of Colombia ordered that a woman living
      with HIV be reinstated in her job at a health clinic in order to respect her
      rights under the national constitution, pending a final determination of the
      merits of her claim of discrimination and other infringement of human rights.

PMID- 15991391
TI  - Australia: appeal court upholds compensation for occupational exposure.
AB  - On 5 August 2004, the New South Wales Court of Appeal upheld a decision ordering
      a medical centre to pay workers' compensation to a physician infected with HIV
      during the course of his employment.

PMID- 15991392
TI  - Ukraine: dismissal on the basis of HIV status ruled unconstitutional.
AB  - On 18 October 2004 the Novosanzhary District Court in Poltava oblast ruled in
      favour of Olexiy Voloshyn, who had been harassed and fired by his employer on the
      basis of his HIV status. The court held that Voloshyn's constitutional rights to
      equality in choice of profession and labour activity, and respect for human
      honour and dignity, had been violated by Viktoriya Dev'yatko, editor-in-chief of
      the Novosanzhary district newspaper.

PMID- 15991394
TI  - Criminal law and HIV transmission/exposure: three new cases.

PMID- 15991393
TI  - South Africa: "HIV-positive" T-shirt leads to dismissal?
AB  - In October 2004 a South African Labour Court dismissed a worker's application for
      unfair dismissal based on "an arbitrary ground including but not limited to the
      applicant's actual or perceived HIV-positive status."

PMID- 15991395
TI  - UK: Court orders reconsideration of asylum case.

PMID- 15991396
TI  - Indian High Court refuses to review challenge to criminalization of
      homosexuality.

PMID- 15991397
TI  - South Africa: Court upholds disciplinary measures against outspoken physician.

PMID- 15991398
TI  - Improving medical students' knowledge of systems-based practice.
AB  - Systems-based practice is an important aspect of medical education. This study
      evaluates the effectiveness of an eight-hour intervention on medical students'
      knowledge of the principles of managed care. A pre-test on basic managed care
      principles was administered to freshman medical students at Mercer University.
      After an eight- hour managed care curriculum was presented to these students, a
      post-test was administered. The pre-test and post-test scores on the material
      increased a mean score of 9.7 points (p < 0.001). Our conclusion is that
      providing as little as eight-hours of instruction on managed care topics can
      significantly improve first-year medical students' knowledge and understanding of
      systems-based practice.

PMID- 15991399
TI  - Novel materials and applications of electronic noses and tongues.
AB  - This introductory article describes the content of the October 2004 issue of MRS
      Bulletin focusing on novel materials and applications of electronic noses and
      tongues. The articles in this issue review the state of the art in materials,
      devices, and data processing algorithms used in electronic olfaction and taste
      systems. The most common gas- and liquid-phase analyte detection tools are
      presented and compared with traditional chemical analysis instrumentation such as
      gas chromatography/mass spectroscopy systems. Metal oxides, polymer/polymer
      composites, and dyes are covered in these articles as key sensing materials.
      Resistive, optical, electrochemical, and other types of electronic nose and
      tongue systems are reviewed, and their use in diverse applications, including
      environmental and food-quality monitoring and medical diagnostics, is discussed.

PMID- 15991400
TI  - Polymer-carbon black composite sensors in an electronic nose for air-quality
      monitoring.
AB  - An electronic nose that uses an array of 32 polymer-carbon black composite
      sensors has been developed, trained, and tested. By selecting a variety of
      chemical functionalities in the polymers used to make sensors, it is possible to
      construct an array capable of identifying and quantifying a broad range of target
      compounds, such as alcohols and aromatics, and distinguishing isomers and
      enantiomers (mirror-image isomers). A model of the interaction between target
      molecules and the polymer-carbon black composite sensors is under development to
      aid in selecting the array members and to enable identification of compounds with
      responses not stored in the analysis library.

PMID- 15991401
TI  - An optoelectronic nose: "seeing" smells by means of colorimetric sensor arrays.
AB  - A new approach to general sensors for odors and volatile organic compounds (VOCs)
      using thin films of chemically responsive dyes as a colorimetric sensor array is
      described. This optoelectronic "nose," by using an array of multiple dyes whose
      colors change based on the full range of intermolecular interactions, provides
      enormous discriminatory power among odorants in a simple device that can be
      easily digitally imaged. High sensitivities (ppb) have been demonstrated for the
      detection of biologically important analytes such as amines, carboxylic acids,
      and thiols. By the proper choice of dyes and substrate, the array can be made
      essentially nonresponsive to changes in humidity.

PMID- 15991403
TI  - Beyond Bland: a critique of the BMA guidance on withholding and withdrawing
      medical treatment.
AB  - In Bland the House of Lords held it lawful to withdraw tube-feeding from a
      patient in a 'persistent vegetative state' (pvs), even with intent to kill him.
      The British Medical Association (BMA) recently published guidance on the
      withholding and withdrawal of 'medical treatment', so defined as to include food
      and water delivered by tube. The guidance endorses the withholding/withdrawal of
      tube-delivered food and water not only from patients in pvs but also from other
      non-terminally ill patients, such as those with severe dementia or serious
      stroke. The underlying justification appears (as in Bland) to be that such lives
      lack worth. This article offers three major criticisms of the guidance. First,
      its argument that tube-feeding is medical treatment rather than basic care is
      weak. Secondly, its reasons for not treating or tube-feeding undermine the BMA's
      long-standing opposition to active euthanasia and active assisted suicide.
      Thirdly, it relies heavily on legal precedent at the expense of ethical
      reasoning.

PMID- 15991402
TI  - [NiFe]-hydrogenases: spectroscopic and electrochemical definition of reactions
      and intermediates.
AB  - Production and usage of di-hydrogen, H2, in micro-organisms is catalysed by
      highly active, 'ancient' metalloenzymes known as hydrogenases. Based on the
      number and identity of metal atoms in their active sites, hydrogenases fall into
      three main classes, [NiFe]-, [FeFe]- and [Fe]-. All contain the unusual ligand CO
      (and in most cases CN- as well) making them intriguing examples of
      'organometallic' cofactors. These ligands render the active sites superbly
      'visible' using infrared spectroscopy, which complements the use of electron
      paramagnetic resonance spectroscopy in studying mechanisms and identifying
      intermediates. Hydrogenases are becoming a focus of attention for research into
      future energy technologies, not only H2 production but also H2 oxidation in fuel
      cells. Hydrogenases immobilized on electrodes exhibit high electrocatalytic
      activity, providing not only an important new technique for their investigation,
      but also a basis for novel fuel cells either using the enzyme itself, or inspired
      synthetic catalysts. Favourable comparisons have been made with platinum
      electrocatalysts, an advantage of enzymes being their specificity for H2 and
      tolerance of CO. A challenge for exploiting hydrogenases is their sensitivity to
      O2, but some organisms are known to produce enzymes that overcome this problem by
      subtle alterations of the active site and gas access channels.

PMID- 15991404
TI  - Who's afraid of Leon Kass?

PMID- 15991405
TI  - Why Ashcroft is wrong on assisted suicide.

PMID- 15991406
TI  - Abortion in America: is compromise possible?

PMID- 15991407
TI  - Commentary: monitoring biological data.

PMID- 15991408
TI  - Ethical and legal issues in scientific data audit and quality assurance.

PMID- 15991409
TI  - The discipline of science: law or profession?

PMID- 15991410
TI  - Honesty and method.

PMID- 15991411
TI  - More gold and more fleece: improving the legal sanctions against medical research
      fraud.

PMID- 15991412
TI  - Autonomy, consent, and the conflict of rights in health care.

PMID- 15991413
TI  - Cardinal Bernardin on the "forgotten factor" and other gaps in the abortion
      debate.

PMID- 15991414
TI  - Americanizing the anti-abortion argument.

PMID- 15991416
TI  - Human gene therapy: an ethical advance?

PMID- 15991415
TI  - Ethical decision making at the end of life: the role of religious traditions and
      public policy.

PMID- 15991417
TI  - After the Cruzan case.

PMID- 15991418
TI  - Rust v. Sullivan: a better debate.

PMID- 15991419
TI  - The first euthanasia referendum.

PMID- 15991420
TI  - The pro-life 'Sophie's Choice'.

PMID- 15991421
TI  - 'Moral considerations' ill considered.

PMID- 15991422
TI  - Three choices for death.

PMID- 15991423
TI  - Fetal brain transplantation: questionable human experiment.

PMID- 15991424
TI  - Cloning: the human as created co-creator?

PMID- 15991425
TI  - Bioethics.

PMID- 15991426
TI  - Bioethics.

PMID- 15991427
TI  - Transgenesis in animal systems: a view from within.
AB  - The introduction of 'foreign' or altered genes into animals arouses both
      scientific and public concern. So too does any extension of this practice to
      human beings at the somatic (tissue) level, let alone interference in the human
      germ line (genetic material passed on to future generations). The range of
      possible genetic modifications, both those in progress and those likely in the
      near future, is so vast as to make a uniform Christian response untenable. As
      with other technologies, there are both laudable and dubious uses for genetic
      engineering in animal systems; it is neither an unmixed blessing nor an
      unmitigated curse. It is argued that Christians should engage with these issues
      on a case-by-case basis, giving due weight to the possible risks and concomitant
      suffering for the animals used, but basing our ultimate approval or disapproval
      on the congruence of means and aims with those evinced by Jesus in his ministry
      of healing, teaching and reconciliation.

PMID- 15991428
TI  - Ethical issues in the application of medical technology to paediatric intensive
      care: two views of the newborn.
AB  - Recent advances in medical technology have led to a marked improvement in the
      chances of survival of sick or preterm infants, thereby stimulating renewed
      ethical debate on the status of the newborn. Two contradictory attitudes to the
      medical care of preterm or congenitally malformed newborn infants can be
      discerned in our pluralistic society. The two attitudes have their historical
      roots in the classical Graeco-Roman and Judaeo-Christian ethical traditions
      respectively. The former views newborn infants as of potential value only whereas
      the latter emphasises the intrinsic worth and dignity of the individual made in
      God's image. Recent secular philosophical reflection has provided a rationale for
      infanticide of the sick or abnormal newborn. A Christian approach to the care of
      the newborn prohibits intentional killing yet may encompass the withdrawal of
      treatment that is inappropriate or unduly burdensome. Medical care should be
      based upon respect for the value of the individual, protection of the defenceless
      from abuse or exploitation, and wise stewardship of limited health-care
      resources.

PMID- 15991429
TI  - Health care rationing?

PMID- 15991430
TI  - Fear of selfing in the American cultural imaginary or "you are never alone with a
      clone".

PMID- 15991431
TI  - Chemical castration: MPA treatment of the sexual offender.

PMID- 15991432
TI  - Stunning progress in stem-cell research.

PMID- 15991433
TI  - Cell-cell interactions may be crucial in HD.

PMID- 15991434
TI  - Rogue prions caught in action.

PMID- 15991435
TI  - Polio vaccination campaign starts in Yemen.

PMID- 15991436
TI  - Cell-cycle inhibitors stop secondary damage after brain injury.

PMID- 15991437
TI  - GABA receptors may mediate hormone-related disorders.

PMID- 15991438
TI  - Connections matter: unravelling gene effects in psychiatry.

PMID- 15991439
TI  - Genetic mutation predisposes to porencephaly.

PMID- 15991440
TI  - Notice of duplicate publication. Octylcyanoacrylate skin closure in laparoscopy.

PMID- 15991441
TI  - [Wonder matter and assassin. The perception of the asbestos danger as a mirror of
      the time 1930-1990].
AB  - In the seventies and eighties of the twentieth century the ideas of the dangers
      concerning the use of asbestos changed dramatically. The mineral, which had, more
      than half a century before been introduced in the Netherlands as a miraculous
      mineral, was completely banned from use. Asbestos became known as a 'silent
      killer' and 'the blue sand of death', and as a symbol of the hidden hazards of a
      deteriorating environment caused by unscrupulous companies and indolent
      authorities. Asbestos seems to fit perfectly into the ubiquitous hazards which
      Ulrich Beck defines in his concept of the 'risk society' as the dangerous side
      effects of industrial production. Yet the perception of the risk associated with
      asbestos depended more on socio-cultural characteristics than on scientifically
      risk assessments. In the first half of the twentieth century the use of asbestos
      was limited and therefore did not cause any concern. Economic crisis and war
      silenced the first alarming signals of asbestos related disease from foreign
      experts and a handful of Dutch physicians. The asbestos workers themselves were
      held responsible for their own health and safety. In the 1951 asbestosis became
      recognised as an industrial disease. Preventive measures with regard to the
      industrial use of asbestos were prescribed by law. Workers shared the
      responsibilities for a safe use with employers and authorities. However, during
      this period, all the attention was directed towards economic growth. Supervision
      by the labour inspection was scarce and workers and employers were not very
      interested in upholding the safety measures. Among asbestos workers the use of
      protective clothes and dust masks was generally seen as unmanly. In the sixties
      the foreign literature on the connection between the exposure to asbestos and the
      occurrence of lung cancer and mesothelioma became known among Dutch specialists.
      The results of these studies were confirmed by research among Dutch insulation
      workers. At the same time the trade unions rejected the idea of a shared
      responsibility and formulated the unilateral 'right to a safe working
      environment', with the implication that, in their view, all unhealthy and unsafe
      procedures should unconditionally be banned from the workshops, including the use
      of asbestos. Concerned civilians, environmental lobbyists, progressive political
      parties and concerned scientists transformed this idea into a 'right to a safe
      living environment', while mass media spread the message. Asbestos was pointed
      out as a threat to the public health, tracked down all of its hiding places and
      ultimately removed. The ban on asbestos was one of the results of democratisation
      and emancipation movement of the late sixties and seventies. The emancipation
      expressed itself in an increasing intolerance to risks brought about by powerful
      companies and bureaucratic authorities.

PMID- 15991442
TI  - Obstetrics and gynecology.

PMID- 15991443
TI  - Minimally invasive total knee arthroplasty.

PMID- 15991444
TI  - Architectures of genetic medicine: comparing genetic testing for breast cancer in
      the USA and the UK.
AB  - This paper compares the development of genetic testing for breast cancer (BRCA
      testing) in the USA and the UK. It argues that national political cultures played
      an important role in how these genetic testing technologies were shaped, and that
      the shapes of these technologies had important implications for the users of
      these systems. In order to demonstrate the roles of national social and political
      elements in the development of new genetic testing technologies, I introduce the
      concept of a technology's architecture, which is made up of components and the
      specific ways in which these components are assembled to fulfill particular
      functions. In the USA, four very different BRCA testing systems initially
      emerged. However, one biotechnology company, Myriad Genetics, eventually used its
      legal and economic position to become the sole provider of testing. It offered
      BRCA testing the way many other laboratory tests were provided in the USA,
      available to anyone through any physician. The shape of this testing service had
      important implications for its participants, defining the client as a consumer
      who could demand access to any of Myriad's laboratory services, but could not
      choose among testing systems. In the UK, the government-run National Health
      Service provided testing through regional genetics clinics, using family history
      information to assess risk and triage care. Clients in the UK were defined as
      citizens and patients, who had the right to equal access to the testing system
      but could not demand any specific services.

PMID- 15991445
TI  - BRCA patients and clinical collectives: new configurations of action in cancer
      genetics practices.
AB  - Since the late 1980s, in France and in a number of other countries, cancer
      genetics testing has become a clinical reality, particularly for hereditary
      breast and ovarian cancer. BRCA tests allowing for the assessment of an increased
      cancer risk among patients and their healthy relatives are now being routinely
      performed as part of clinical practice. Based on fieldwork on French clinical
      cancer genetics and on the French Cancer Genetics Collaborative Network, this
      paper examines the configuration of entities, actors and activities mobilized by
      the performance of BRAC testing, and argues that the development of clinical
      molecular genetic practices is predicated upon the development of new forms of
      collaborative work that lead to a transformation of the content and organization
      of medical activities and judgements. The paper analyses three major collective
      configurations - local multidisciplinary collectives, data collectives and new
      clinical collectives - and argues that they not only provide the material
      conditions needed to carry out the relevant activities, but also articulate a
      series of distinctive bio-clinical interventions. These interventions provide an
      interface with research activities, produce the epidemiological measurements and
      tools that are a sine qua non for clinical work in this field, and, most
      importantly, establish the conventions that underlie practices, which define the
      criteria that turn tools and novel entities into operational components of
      clinical settings. It thus appears that in the field of clinical cancer genetics,
      bioclinical collectives, as a locus of expertise, have replaced the individual
      judgement of the practicing clinician.

PMID- 15991446
TI  - The 'Book of Life' in the press: comparing German and Irish media discourse on
      human genome research.
AB  - The essay compares German and Irish media coverage of human genome research in
      the year 2000, using qualitative and quantitative frame analysis of a print media
      corpus. Drawing from a media-theoretical account of science communication, the
      study examines four analytic dimensions: (1) the influence of global and national
      sources of discourse; (2) the nature of elaboration on important themes; (3) the
      extent of societal participation in discourse production; (4) the cultural
      conditions in which the discourse resonates. The analysis shows that a global
      discursive package, emphasizing claims of scientific achievement and medical
      progress, dominates media coverage in both countries. However, German coverage is
      more extensive and elaborate, and includes a wider range of participants. Irish
      coverage more often incorporates the global package without further elaboration.
      These finding indicate that the global package is 'localized' differently due to
      national patterns of interests, German participation in human genome research,
      traditions of media coverage, and the domestic resonance of the issue.

PMID- 15991447
TI  - Rethinking scientific specialization.
AB  - My aim in this paper is to re-examine specialization in science. I argue that we
      need to acknowledge the role that conceptual changes can play in the creation of
      new specialties. Whereas earlier sociological accounts focus on social and
      instrumental changes as the cause of the creation of new specialties, I argue
      that conceptual changes play an important role in the creation of some scientific
      specialties. Specifically, I argue that conceptual developments played an
      important role in the creation of both endocrinology and virology.

PMID- 15991448
TI  - [To the adoption of von Hallers medical and medical history work in the 19th and
      20th centuries].
AB  - A survey of the secondary literature of Albrecht Haller's medical work after his
      death (1777) reveals that already in the 19th century most of his topics and his
      methods were discussed and appreciated. Within physiology his doctrine of
      irritability and sensibility received most attention. The 20th century shows a
      considerable expansion of the secondary literature. However, there is still a
      lack of monographs dealing with Haller's medical work in a comprehensive way. Not
      only was the appreciation of Haller's medical work in the more than 200 years
      since his death constantly high but, for whatever reasons, it is even
      characterized by an increasing interest of researchers from many fields.

PMID- 15991449
TI  - Russian-American pharmaceutical relations, 1900-1945.
AB  - Many books and articles have focused on Soviet health-care. But there are no
      studies of the Soviet pharmaceutical industry, which was a lynch-pin of Soviet
      medicine, for without therapies physicians and health-care personnel can only
      diagnose, not treat. The present paper, part of such a study, opens a window onto
      one small aspect of the Soviet pharmaceutical industry - points of congruence,
      divergence, and reconvergence in the pharmaceutical sector with an on-again, off
      again political and economic rival. This paper briefly reviews the Russian and
      the Soviet pharmaceutical systems, so that American audiences can make a
      comparison of them with our own. It then examines American-Russian/Soviet
      interaction in trade, joint ventures, research and development, product mix, and
      connections during World War II to illustrate similarities and differences.
      During the last decade, although the Soviet and American pharmaceutical systems
      each had a different trajectory of development, ironically their pharmaceutical
      industries again are finding points in common.

PMID- 15991450
TI  - "A Bit of Honest Information": pharmacy in an industrial eastern city in the
      early twentieth century.

PMID- 15991451
TI  - Jacob Bigelow's American Medical Botany: digital reissue illuminates access to
      rare work.

PMID- 15991452
TI  - Freeing the human spirit.

PMID- 15991453
TI  - The battle for top-drawer managers.

PMID- 15991454
TI  - Complying with OIG's 2002 work plan.

PMID- 15991455
TI  - Focus on caregiving: where quality care begins.

PMID- 15991456
TI  - Applying DALY to assessing national health insurance performance: the
      relationship between the national health insurance expenditures and the burden of
      disease measures in Iran.
AB  - The Iranian government has considered using DALYs as an indicator to prioritize
      health service expenditures to reduce the burden of disease for the public. A
      cross-sectional study was designed to compare several measures of the burden of
      disease with the actual amounts of national health insurance (NHI) expenditures,
      in one province of Iran (Semnan) for a period of 2 months (September 2000 and
      February 2001). Furthermore, on the basis of the research findings, a
      questionnaire was designed and distributed to stakeholders at local and national
      levels to explore their ideas about the gap between the expenditures of the
      diseases group and their burden. A semi-structured interview was conducted to
      elicit participants' views on the research findings. The results of this study
      have revealed that, currently, there is no strong relation between the NHI
      expenditures and DALY (r = 0.41, p = 0.09), but that there are stronger
      relationships between the amounts of NHI reimbursements with YLL (r = 0.52, p <
      0.05), mortality (r = 0.67, p < 0.01) and hospital days (r = 0.90, p < 0.01).
      Comparing each group of disorders' DALY with the resources allocated to them
      (cost per DALY) it was shown that diabetes mellitus, musculoskeletal diseases,
      maternal conditions, sense organ disorders received considerably generous
      funding; and, perinatal conditions, congenital abnormalities, nutritional
      deficiencies were relatively under-funded. The qualitative research results
      showed that the majority of respondents agreed that the differences presently
      existing between disorders' burden and NHI expenditures cannot be justified; and,
      further, that reducing the overall burden of disease must be one of the most
      important objectives for the NHI.

PMID- 15991457
TI  - Managed health care plans in Southern United States municipalities: empirical
      evidence on choice of plan.
AB  - This study examines factors that influence choice of Southern municipal
      government health care plans in the United States. Using survey data, this
      article specifically examines the managed care offerings of Health Maintenance
      Organizations (HMO), Preferred Provider Organizations (PPO) and Point of Service
      (POS) plans. Some of the more interesting empirical results indicate that HMO
      plans are associated more with employee satisfaction; PPO plans are associated
      with cost containment; and POS plans are more likely to provide health care
      benefits to part-time employees. Empirical evidence also indicates that employee
      satisfaction is increased when there is a greater choice of managed care plans
      available to municipal governments.

PMID- 15991458
TI  - The role of user charges and structural attributes of quality on the use of
      maternal health services in Morocco.
AB  - Health care decision makers in settings with low levels of utilization of primary
      services are faced with the challenge of balancing the sometimes competing goals
      of increasing coverage and utilization of maternity services, particularly among
      the poor, with that of ensuring the financial viability of the health system.
      Morocco is a case in point where this policy dilemma is currently being played
      out. This study examines the role of household out-of-pocket costs and structural
      attributes of quality on the use of maternity care in Morocco using empirical
      data collected from both households and health care facilities. A nested logit
      model is estimated, and the coefficient estimates are used to carry out policy
      simulations of the impact of changes in the levels of out-of-pocket fees and
      structural attributes of quality in order to help guide policy makers responsible
      for the design of pending social insurance programs. The results of the paper
      suggest that social insurance strategies that involve increases in out-of-pocket
      charges in the form of copayments could be implemented without untoward effects
      on appropriate use of maternity care for non-poor women, but would be
      contraindicated for poorer and rural households.

PMID- 15991459
TI  - Where does the US experience of managed care currently stand?
AB  - After an historical review of the advent of managed care in the USA, this article
      presents cost-control mechanisms, changes in the medical practice and
      consequences on patient health. The article also explains the development of the
      HMO using the transaction costs theory and the subsequent orientations of the US
      health care system.

PMID- 15991460
TI  - Sustainable partnerships for integrated care: the role of decision making and its
      environment.
AB  - This paper is intended to further the understanding of the role of the
      characteristics of decision making and its environment in the development of
      sustainable partnerships in health care, and to illustrate how this subject can
      be studied from a combined theoretical and methodological perspective. With the
      aid of a conceptual model covering sensitizing concepts from contingency theory
      (that refer to environmental characteristics--particularly institutions--the
      process course of decision making and its outcomes) and the case study
      methodology (explanation-building, triangulation, document study and interviews),
      two Dutch cases were analysed. The findings indicate which environmental
      characteristics are responsible for the differences in the process course and
      outcomes between the cases.

PMID- 15991461
TI  - Evidences on weaknesses and strengths from health financing after
      decentralization: lessons from Latin American countries.
AB  - OBJECTIVE: The main objective was to identify trends and evidence on health
      financing after health care decentralization. STUDY DESIGN: Evaluative research
      with a before-after design integrating qualitative and quantitative analysis.
      Taking into account feasibility, political and technical criteria, three Latin
      American countries were selected as study populations: Mexico, Nicaragua and
      Peru. DATA SOURCES: The methodology had two main phases. In the first phase, the
      study referred to secondary sources of data and documents to obtain information
      about the following variables: type of decentralization implemented, source of
      finance, funds of financing, providers, final use of resources and mechanisms for
      resource allocation. In the second phase, the study referred to primary data
      collected in a survey of key personnel from the health sectors of each country.
      FINDINGS: The trends and evidence reported in all five financing indicators may
      identify major weaknesses and strengths in health financing. CONCLUSIONS:
      Weaknesses: a lack of human resources trained in health economics who can
      implement changes, a lack of financial resource independence between the local
      and central levels, the negative behavior of the main macro-economic variables,
      and the difficulty in developing new financing alternatives. Strengths: the
      sharing between the central level and local levels of responsibility for
      financing health services, the implementation of new organizational structures
      for the follow-up of financial changes at the local level, the development and
      implementation of new financial allocation mechanisms taking as a basis the
      efficiency and equity principles, new technique of a per-capita adjustment factor
      corrected at the local health needs, and the increase of financing contributions
      from households and local levels of government.

PMID- 15991462
TI  - [Aortic stenosis].

PMID- 15991463
TI  - [Dobutamine hemodynamics for aortic stenosis with left ventricular dysfunction].
AB  - Patients with aortic stenosis (AS) and left ventricular (LV) systolic dysfunction
      have a poor short-term prognosis. In this setting, the decrease in transaortic
      gradients has an independent prognostic value for operative risk and long-term
      outcome. The 2 main issues for these patients are: (1) The real severity of AS;
      (2) How to stratify operative risk and evaluate long-term prognosis. Dobutamine
      Hemodynamics has the potential to address these issues. In case of relative AS,
      valve area is increased by dobutamine (final valve area > 1.2 cm2 with a mean
      pressure gradient <30 mmHg); on the basis of published data, medical treatment is
      justified in this case. Left ventricular contractile reserve is defined an
      increase in stroke volume, by 20% or more, under dobutamine. Operative risk is
      between 5 and 11% in case of LV contractile reserve and long-term outcome is
      improved by surgery in this case. In contrast, operative risk varies from 30 to
      60% in case of exhausted reserve; this risk is also determined by other factors
      such as the presence of coronary artery disease and associated comorbidities. All
      these parameters are factored into risk-benefit analysis in order to determine
      the best therapeutic approach for each patient.

PMID- 15991464
TI  - [Recommendations for noncardiac surgery in aortic stenosis].
AB  - Aortic stenosis (AS) is the most common valve disease in western countries and
      its prevalence increases with population aging. AS is an important risk factor
      for perioperative complications in patients undergoing noncardiac surgery, a
      common situation in older patients. Preoperative evaluation should be based on a
      careful cardiac and general examination (risk factors and comorbidities) as well
      as on the type and urgency of the noncardiac surgery (urgent as opposed to
      elective). Careful teamwork and communication between the cardiologist, the
      anesthesiologist and the surgeon is mandatory. It is also critical that the
      anesthesiologist team is used to managing these high-risk patients. In cases of
      non-severe AS (>0.6 cm2/m2 of body surface area), the noncardiac surgery can be
      performed first. If AS is severe (< or =0.6 cm2/m2) and the noncardiac surgery
      elective, it is appropriate to consider an aortic valve replacement first. In the
      difficult cases of urgent noncardiac surgery in patients with severe AS, which
      precludes heart surgery, it is possible either to first proceed with the
      noncardiac surgery under very careful anesthesiologic management or to perform
      the percutaneous aortic valve commissurotomy first.

PMID- 15991465
TI  - [When should one operate for severe asymptomatic aortic stenosis?].
AB  - The most common cause of aortic stenosis is degenerative and progression of the
      disease is slow. Deciding to proceed to aortic valve replacement in an
      asymptomatic patient is always difficult. Only a minority will require valve
      replacement after repeated work-ups including stress testing and serial
      echographic examinations. In the future, stress echocardiography and BNP
      measurements may prove helpful in decision making.

PMID- 15991466
TI  - [Surgical treatment of aortic stenosis: which prosthesis for which patient?].
AB  - The long-term evolution following aortic valve replacement depends on the
      specific clinical context for each patient, but also on the type of prosthesis
      used. The increased hemorrhagic risk with mechanical prosthesis has to be weighed
      against the long-term risk of structural failure of bioprostheses. The patient's
      age will be a key determinant in the choice of the best suited prosthesis.
      Usually, bioprostheses are preferred after 70 years of age, while mechanical
      prostheses are chosen in patients under 65.

PMID- 15991467
TI  - [Mild aortic stenosis and coronary bypass surgery].
AB  - The presence of mild to moderate aortic stenosis in a patients scheduled for
      coronary bypass surgery poses difficult problems with respect to the optimal
      therapeutic strategy. The first step is obviously to obtain a precise
      quantification of the degree of stenosis. Whenever possible, confrontation with
      previous echo examinations will provide an idea of the speed with which aortic
      stenosis progresses. The cardiologist, together with the cardiac surgeon, will
      have to carefully balance the operative risk and the risk of a second
      intervention. The patient's age will be central in the discussion, as it is a
      major determinant of life expectancy after the initial intervention.

PMID- 15991468
TI  - [Severity of aortic ring abscess complicated by cardiac conduction
      abnormalities].
AB  - OBJECTIVE: To determine clinical features, management and prognosis of cardiac
      conduction abnormalities (CCA) complicating abscessed endocarditis. METHODS: We
      have analysed clinical, microbiologic and echocardiographic datas, therapies and
      outcome of cardiac abscesses complicated by CCA in patient hospitalized between
      1995 and 2001 in our centre. RESULTS: Above 35 cardiac abscesses, six men (mean
      age 62 years) had CCA complicating six aortic ring abscesses (4 on native valve
      and 2 on prosthetic valve) with four cases of interventricular septal involvement
      and fistulization. Severe heart failure is present four times, a septic cerebral
      embolization twice. Streptococcus and Staphylococcus prevail. Complete
      atrioventricular block (AVB) reveals endocarditis twice and complicates the
      evolution three times. Trifascicular block (first degree AVB, left anterior
      fascicular block and complete right bundle branch block) revealed recurrence of
      endocarditis. Two patients were treated medically: one died quickly (complete AVB
      pre-mortem), and the other one had favourable issue (paroxystic complete AVB).
      Four patients had surgery with temporary pacemaker in three cases (one died) then
      definitive pacemaker in two cases. At 26.5 month (7-50), the four survivors had
      no recurrence of endocarditis. CONCLUSION: Severe CCA are classical in aortic
      ring abscessed endocarditis and associated with increased mortality. Immediate
      transfert in a dentre with cardiac surgery is necessary. Definitive cardiac
      pacing can be performed early without leads infection.

PMID- 15991469
TI  - [Infective endocarditis: a potential complication of subaortic membranes].

PMID- 15991470
TI  - [Cardiac surgery after liver transplantation].
AB  - An aortic valve replacement and an aorto-coronary bypass were done in a woman of
      57 years old after an orthotopic liver transplantation. The surgical risk was
      increased by the antecedent liver transplantation, the immunosuppression, chronic
      renal insufficiency and antiphospholipid syndrome. Surgery and the post-operative
      period were not complicated. Cardiac surgery is not a contraindication for
      patients with a prior organ transplant. These individuals have a higher
      cardiovascular risk and require a cardiovascular follow-up the modalities of
      which are yet to be defined.

PMID- 15991471
TI  - [The adenosine-5'-triphosphate (ATP) test: a diagnostic tool in the management of
      syncope of unknown origin. Basic and clinical aspects].
AB  - The prevalence of syncope increases in elderly population. An inappropriate
      reflex reaction of the autonomous nervous system in specific circumstances is
      responsible for symptoms in more than 50% of cases. These neurocardiogenic or
      vasovagal syncopes are due to a vasoplegia or to a cardio-inhibitory reflex or to
      the association of both mechanisms. Reproducing the symptoms may contribute to
      identify the responsible mechanism of syncope; this objective is partly reached
      by the head-up tilt test--a provocative test--which reproduces symptoms in about
      half of the cases, mainly by provoking a severe vasodilation with fall of blood
      pressure. On the opposite, the ATP test (20 mg i.v. bolus)--a descriptive test-
      provokes a strong cardio-inhibitory reflex independent from external factors like
      body position but it must be undertaken in a calm environment for preventing any
      anticipative sympathetic reaction. The test is considered positive if ATP
      produces a cardiac pause longer than 10 seconds and related symptoms are not
      taken into account for assessing the final result. ATP test positivity increases
      with age and with the presence of cardiac diseases. Permanent dual chamber pacing
      at 70 bpm has been shown to reduce significantly the syncope recurrences in
      patients with positive ATP test and to have no influence on patients with a
      negative test. The use of ATP test should be extended to all syncope screening.
      Its positivity identifies a group of patients in whom the mechanism of the
      syncope is susceptible to be improved by a permanent dual chamber pacing.

PMID- 15991472
TI  - [Review: genetics of familial dilated cardiomyopathy].
AB  - Dilated cardiomyopathy is the most frequent cardiomyopathy. Twenty to 35% of
      dilated cardiomyopathies are familial. The transmission of the disease is most
      frequently dominant autosomic. Dilated cardiomyopathy is genetically
      heterogeneous. Hence, mutations have been identified on 14 genes, and 9 loci have
      been associated to familial dilated cardiomyopathy. The incriminated mechanisms
      in the pathogeny of dilated cardiomyopathy include mutations on proteins of the
      sarcomere, the cytosqueletton, the nuclear membrane or involved in calcium
      signaling. This review indicates the genes and proteins implicated in the
      pathogeny of familial dilated cardiomyopathy, and their potential clinical
      effects.

PMID- 15991473
TI  - [Validation of a multiplex PCR for detection of Shiga toxin-producing Escherichia
      coli].
AB  - Shiga toxin-producing Escherichia coli (STEC) cause non-bloody or bloody
      diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS) in humans. The
      aim of the present study was to validate a multiplex PCR for the STEC diagnosis
      based on the detection of stx1, stx2 and rfbO157 genes. The multiplex PCR
      validation was carried out in two independent laboratories in a parallel way.
      Work range, selectivity and robustness were established. The PCR performance was
      evaluated using different concentrations of two STEC strains harboring different
      target genes. The work range depended on the strain analyzed, the maximum and the
      minimum values were 6.6 x 10(7) and 1.0 x 10(4) CFU/50 microl. The detection
      limit was 1.0 x 10(4) CFU/50 microl and the cut limit 1.0 x 10(5) CFU/50 ml. A
      good robustness was observed when different variables were introduced.
      Inclusivity, exclusivity, positive predictivity, negative predictivity and
      analytical accuracy were of 100%. Interference was not shown when different
      concentrations of STEC strains, carrying different genes, were used. The
      validated technique is an appropriate alternative for detection and confirmation
      of STEC O157 and non-O157 strains from bacterial cultures.

PMID- 15991474
TI  - Comparative molecular study of Mycobacterium tuberculosis strains, in times of
      antimicrobial drug resistance.
AB  - Strains of Mycobacterium tuberculosis were compared using two DNA fingerprinting
      techniques: Restriction Fragment Length Polymorphism (RFLP) and Double-Repetitive
      Element-PCR (DRE-PCR). Two of these strains: IH1 (susceptible to isoniazid) and
      IH2 (resistant to isoniazid) were recovered from cases of pulmonary tuberculosis
      which occurred in two brothers who lived together. The first one was recognized
      on July 1999, and the second was diagnosed one year later. IH1 and IH2 showed the
      same pattern of bands with both molecular tests. These results suggest that
      single drug chemoprophylaxis may occasionally select resistant strains for that
      drug, which can eventually cause disease and be recognized through these tests.
      Strains IH3, IH4 and IH5 were obtained from sputum samples of 3 different
      patients, and intra-laboratory cross-contamination was suspected when it was
      realized that the 3 positive materials had been consecutively processed the same
      day by the same worker in the same biological safety cabinet. Again, the 3
      strains revealed identical band patterns with RFLP and DRE-PCR, confirming the
      posed suspicion. The results with DRE-PCR were obtained after only 8 hours of
      work, without the need for subcultures. This procedure allows quick correction of
      treatment conducts, avoiding unnecessary exposure of people and bacteria to
      antimicrobial drugs.

PMID- 15991475
TI  - [Comparison of different methods for species identification of genus Candida].
AB  - Different species of genus Candida can cause a wide range of pathologies, since
      mucocutaneous trivial infections to disseminated serious forms. Traditionally,
      taxonomy of yeast has been performed taking into account morphologic and
      physiologic studies, but they depend on the culture conditions of strains, what
      cause certain difficulties. Thus, recently, molecular biology methods have been
      tried. The aim of this work is to correlate taxonomic studies of most important
      pathogenic species--C. albicans, C. krusei, C. parapsilosis, C. tropicalis and C.
      glabrata--all of them performed by phenotypic traditional methods, commercial
      ones, and by a molecular method, PCR fingerprinting. Comparing useful methods for
      C. albicans identification, corn flour agar and germinative tube formation, no
      statistical differences between them are observed (chi2 = 0.5, p = 0.4795). By
      comparison between methods to discriminate different Candida species,
      physiological tests, CHROMagar, API 20C and PCF fingerprinting we observed no
      significative differences in proportion of accurate results, in test that can
      identify any Candida species, such as physiological assays, API 20C and PCR
      fingerprinting. The proportion of unequivocal results is greater than the
      obtained performing the CHROMagar culture method (p < 0.001).

PMID- 15991476
TI  - [Recovery of Veillonella from saliva].
AB  - Veillonella spp. are anaerobic gram-negative cocci associated to oral health.
      Different types of cultures have been reported for the isolation of these
      microorganisms. Veillonella spp. colonies produce a red fluorescence, which is
      made visible through ultraviolet light and disappears in contact with oxygen.
      This feature would be very useful for rapid presumptive identification. The aims
      of this study were: 1. to compare the Rogosa selective medium for Veillonella
      with the cultures recommended by different authors in order to determine best
      saliva recovery, since this sample is generally used to determine the presence
      and predominance of this bacteria; 2. to detect red fluorescence production on
      these different culture media as a rapid method for identification. Selective
      medium for Veillonella, Schaedler agar for anaerobic bacteria with vitamin K,
      thioglycollate agar, brain heart infusion agar, Brucella agar, trypticase soy
      agar, and Columbia agar, all of them with and without the addition of vancomycin,
      and laked blood were used for this study. The tested sample was a saliva pool.
      Both, Veillonella colonies, and the total number of microorganisms were counted,
      and expressed as CFU/ml of saliva. The greatest Veillonella recovery in saliva
      was obtained with the selective medium for Veillonella with vancomycin and laked
      blood. The production of fluorescence was only observed in this medium.

PMID- 15991477
TI  - [Clinical and epidemiologic analysis of intestinal tract colonization with
      vancomycin-resistant enterococci in an intensive care unit].
AB  - Intestinal tract colonization with vancomycin resistant enterococci (VRE) was
      studied during five months and 25 days. Out of 171 patients hospitalized in the
      intensive care unit, 124 (73%) were included in this study. Thirty five of them
      (28%) were recognized as colonized with VRE. VRE isolates (n = 35) were
      identified as Enterococcus faecium (n = 18), Enterococcus gallinarum (n = 16),
      and Enterococcus raffinosus (n = 1). All of them were resistant to vancomycin
      (MIC90 = 512 microg/ml) and to teicoplanin (MIC90 = 32 microg/ml), having the
      vanA gene. By means of molecular methods a high homology was found among E.
      faecium and E. gallinarum isolates, respectively, suggesting their spread as a
      kind of outbreak. No significant differences in age or sex were found among
      colonized and non-colonized patients (p > 0.05). On the other hand, the
      hospitalization time and the use of broad-spectrum antibiotics were associated
      with colonization. From this study we highlight the importance of enhancing all
      measures of control and prevention of hospital infections, carefully analyzing
      the empiric antimicrobial schemes, trying to reduce the hospital stage, and
      following the surveillance to evaluate the efficacy of such procedures.

PMID- 15991478
TI  - ['In vitro' activity of different antimicrobial agents on Gram-negative
      nonfermentative bacilli, excluding Pseudomonas aeruginosa and Acinetobacter spp].
AB  - Gram-negative nonfermentative bacilli (NFB) are widely spread in the environment.
      Besides of difficulties for identification, they often have a marked
      multiresistance to antimicrobial agents, including those active against
      Pseudomonas aeruginosa. The objective of this study was to evaluate the 'in
      vitro' activity of different antimicrobial agents on 177 gram-negative
      nonfermentative bacilli isolates (excluding Pseudomonas aeruginosa and
      Acinetobacter spp.) isolated from clinical specimens. Minimum inhibitory
      concentrations (MIC) were determined according to the Mueller Hinton agar
      dilution method against the following antibacterial agents: ampicillin,
      piperacillin, piperacillin-tazobactam, sulbactam, cefoperazone, cefoperazone
      sulbactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, colistin,
      gentamicin, amikacin, trimethoprim-sulfamethoxazole, chloramphenicol,
      erythromycin, rifampin, norfloxacin, ciprofloxacin and minocycline. Seven
      isolates: Sphingobacterium multivorum (2), Sphingobacteriumspiritivorum (1),
      Empedobacterbrevis (1), Weeksella virosa (1), Bergeyella zoohelcum (1) and
      Oligella urethralis (1), were tested for amoxicillin-clavulanic acid and
      ampicillin-sulbactam susceptibility, and susceptibility to cefoperazone or
      sulbactam was not determined. Multiresistance was generally found in
      Stenotrophomonas maltophilia, Burkholderia cepacia, Chryseobacterium spp.,
      Myroides spp., Achromobacter xylosoxidans, and Ochrobactrum anthropi isolates. On
      the other hand, Pseudomonas stutzeri, Shewanella putrefaciens-algae, Sphingomonas
      paucimobilis, and Pseudomonas oryzihabitans, Bergeyella zoohelcum, Weeksella
      virosa and Oligella urethralis were widely susceptible to the antibacterial
      agents tested. As a result of the wide variation in antimicrobial susceptibility
      shown by different species, a test on susceptibility to different antibacterial
      agents is essential in order to select an adequate therapy. The marked
      multiresistance evidenced by some species, prompts the need to develop new
      antimicrobial agents active against this group of bacteria and to search for
      synergistic combinations.

PMID- 15991479
TI  - [First isolation of Histoplasma capsulatum from the urban bat Eumops
      bonariensis].
AB  - We report the first isolation of Histoplasma capsulatum var. capsulatum from a
      male bat Eumops bonariensis captured in Buenos Aires city in 2003. The pathogen
      was recovered from spleen and liver specimens, and was identified by its
      phenotypic characteristics. PCR with primers 1283, (GTG)5, (GACA)4 and M13 was
      used to compare both bat isolates with 17 human isolates, 12 from patients
      residing in Buenos Aires city, and 5 from other countries of the Americas. The
      profiles obtained with the four primers showed that both bat isolates were
      identical to each other and closer to Buenos Aires patients than to the other
      isolates (similarity percentage: 91-100% and 55-97%, respectively). The high
      genetic relationship between bat isolates and those from patients living in
      Buenos Aires suggests a common source of infection. This is the first record of
      E. bonariensis infected with H. capsulatum in the world, and the first isolation
      of the fungus in the Argentinean Chiroptera population. In the same way as these
      wild mammals act as reservoir and spread the fungus in the natural environment,
      infection in urban bats could well be associated with the increase in
      histoplasmosis clinical cases among immunosuppressed hosts in Buenos Aires city.

PMID- 15991481
TI  - Getting to grips with statistics.

PMID- 15991480
TI  - [Consensus for antimicrobial susceptibility testing for Enterobacteriaceae.
      Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical
      Bacteriology), Argentinian Association of Microbiology].
AB  - Taking into account previous recommendations from the National Committee for
      Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad
      Argentina de Bacteriologia Clinica (SADEBAC), Asociacion Argentina de
      Microbiologia (AAM), and the experience from its members and some invited
      microbiologists, a consensus was obtained for antimicrobial susceptibility
      testing and interpretation in most frequent enterobacterial species isolated from
      clinical samples in our region. This document describes the natural antimicrobial
      resistance of some Enterobacteriaceae family members, including the resistance
      profiles due to their own chromosomal encoded beta-lactamases. A list of the
      antimicrobial agents that should be tested, their position on the agar plates, in
      order to detect the most frequent antimicrobial resistance mechanisms, and
      considerations on which antimicrobial agents should be reported regarding to the
      infection site and patient characteristics are included. Also, a description on
      appropriate phenotypic screening and confirmatory test for detection of prevalent
      extended spectrum beta-lactamases in our region are presented. Finally, a summary
      on frequent antimicrobial susceptibility profiles and their probably associated
      resistance mechanisms, and some infrequent antimicrobial resistance profiles that
      deserve confirmation are outlined.

PMID- 15991482
TI  - Early cycling test as a predictor of walking performance in stroke patients.
AB  - BACKGROUND AND PURPOSE: To assess the relative contribution and the predictive
      value of an early cycling test to walking performance three months after stroke.
      METHOD: This follow-up study included subjects who were inpatients after afirst
      stroke (n=44). A cycling test was performed at the beginning of rehabilitation,
      followed by three-months' post-stroke evaluation of walking performance. The
      independent variables were the ability to cycle at constant rhythm of 50 rpm,
      without and with resistance, lower extremity motor strength and walking function,
      scored by the Scandinavian Stroke Scale. Dependent variables were gait velocity,
      distance and stair-climbing three months after stroke. RESULTS: Multiple linear
      regression analysis demonstrated that rhythmic, constant cycling is the best
      predictor of walking velocity (r2 = 0.4), gait distance (r2 = 0.2) and number of
      stairs climbed (r2 = 0.26). Lower extremity motor strength and walking function
      had no additional separate contribution to the prediction of study outcomes.
      CONCLUSIONS: The inability to cycle at a constant rhythm for one minute, two
      weeks after stroke is a more significant predictor than lower extremity motor
      strength or walking function of walking performance at three months post-stroke.

PMID- 15991483
TI  - The relationship between the Activities-specific Balance Confidence Scale and the
      Dynamic Gait Index in peripheral vestibular dysfunction.
AB  - BACKGROUND AND PURPOSE: People with vestibular dysfunction experience dizziness,
      vertigo and postural instability. The persistence of these symptoms may result in
      decreased balance confidence. The purpose of the present study was to examine the
      relationship between decreased balance confidence and gait dysfunction in
      patients with unilateral peripheral vestibular dysfunction. METHOD: A
      retrospective review of 137 charts with the Activities-specific Balance
      Confidence (ABC) Scale and the Dynamic Gait Index (DGI) scores was completed.
      Spearman rank-order correlation analysis was performed of the total sample, by
      age group and by degree of vestibular weakness. RESULTS: A moderate correlation
      of r = 0.58 (p < 0.001) was found between the ABC Scale score and the DGI score
      in the total sample. Those with mild or moderate vestibular weakness had a
      correlation of r = 0.72 (p < 0.001) between the ABC Scale score and the DGI
      score, compared with a correlation of r = 0.48 in those with severe or total
      vestibular weakness. CONCLUSIONS: Decreased balance confidence and increased fall
      risk are critical issues for people with vestibular dysfunction. The effects of
      aging did not have a significant impact on the relationship. The correlation
      between balance confidence and gait dysfunction was stronger in those with mild
      or moderate vestibular weakness, although those with severe or total weakness
      were more disabled by their vestibular symptoms.

PMID- 15991484
TI  - Expectations and satisfaction of patients with low back pain attending a
      multidisciplinary rehabilitation service.
AB  - BACKGROUND AND PURPOSE: To identify the expectations of service, and degree of
      satisfaction, with a multidisciplinary service for patients with low back pain,
      and to examine the strength of association between patients' satisfaction and
      expectations. METHOD: A three-stage study design was used. concerns were
      identified by a focus group; priority issues were identified by ranking by use of
      a Delphi consensus questionnaire; satisfaction or expectation questionnaires were
      also used to rate patients' satisfaction and the degree to which expectations
      were met. SUBJECTS: Three convenience samples of patients with low back pain were
      recruited. Ten patients attended the focus group, 55 completed the Delphi
      consensus questionnaire and 40 completed the satisfaction or expectation
      questionnaires. RESULTS: Patients rated a clear diagnosis and effective treatment
      as important, and the ease with which they could access the service and post
      discharge follow-up as important issues when judging satisfaction. Patients rated
      their overall satisfaction and meeting their expectations higher than specific
      service issues, and the strengths of the associations between the two constructs
      varied from concern to concern. CONCLUSION: Certain aspects of service provision
      are rated with greater importance than others when patients judge a service they
      have experienced. There are differences in the strength of associations between
      the constructs of patient satisfaction and meeting expectations of service,
      specific to the individual service concern that is being evaluated. The present
      study provides more evidence that specific concerns within service provision
      should be identified before evaluating patients' expectations and satisfaction
      with the service overall.

PMID- 15991485
TI  - Cardiovascular responses to short-term head-down positioning in healthy young and
      older adults.
AB  - BACKGROUND AND PURPOSE: Isolated head-down postural drainage is assumed to
      acutely load the cardiovascular system. Consequently, it is considered a relative
      contraindication in the presence of severe cardiovascular disease. Evidence
      demonstrating that the head-down manoeuvre as used by physiotherapists does
      significantly load the cardiovascular system is lacking. The present study
      documents the cardiovascular responses t short-term 30 degrees head-down
      positioning in healthy subjects. The results are a point of reference for
      respiratory patients with and without cardiovascular disease. METHOD: A quasi
      experimental research design was used, with multiple measurements obtained at
      rest (long sitting and in the head-down position. Twenty-one young subjects (mean
      age 25 years (standard deviation, (SD) 3 years)) and 19 older subjects (mean age
      66 years (SD 6 years)) were studied. Applanation tonometry and
      sphygmocardiography were used to measure temporal and pressure variables, and
      indices that estimate myocardial work and coronary blood flow. RESULTS: Absolute
      differences existed between the two age groups for all variables at rest (p <
      0.001). No age-time interaction was observed for any variable in the head-down
      position (p > 0.05). Serial measures in the head-down position did not vary
      across time (p > 0.05). Small (<9%) but significant (p < or = 0.02) decreases in
      heart rate, relative diastolic duration, mean arterial blood pressure and
      diastolic time indices, and small (<12%) but significant (p < or = 0.002)
      increases in cardiac cycle time, ejection duration (relative and absolute) and
      absolute diastolic duration were observed in the head-down position compared with
      rest. A small (9%) but significant (p < 0.001) fall in the sub-endocardial
      viability ratio occurred in the head down position. CONCLUSION: The findings have
      little consequence in health, but they suggest that head-down postural drainage
      may be of concern for chest physiotherapy recipients with reduced cardiac reserve
      or impaired barorefilex function.

PMID- 15991486
TI  - Case report: unravelling the complexities of hypertonia and spasm: a piece of
      detective work.

PMID- 15991487
TI  - Physiotherapy and spinal nerve adhesion: a caution.

PMID- 15991488
TI  - Why is the functional independence measure used to identify some rehabilitation
      needs in stroke survivors when there are better tools?

PMID- 15991489
TI  - Mefloquine resistance reversal action of ketoconazole - a cytochrome P450
      inhibitor, against mefloquine-resistant malaria.
AB  - Plasmodium knowlesi (W1) shows a high level of innate resistance to mefloquine as
      shown by recrudescence of blood-induced infection in rhesus monkeys, following
      oral mefloquine treatment with up to 80-160 mg/kg total dose over 3-4 days.
      Ketoconazole, at a dose of 75 mg/kg/day x 10 days given orally to P. knowlesi
      infected rhesus monkeys, exerted a suppressive antimalarial effect in 1 of the 2
      monkeys as evidenced by a delayed recrudescence (on day 30) and curative action
      in case of the other monkey, whereas a lower dose of ketoconazole (25 mg/kg/day x
      10 days) failed to suppress infection effectively. When ketoconazole at a low
      dose (25 mg/kg/day x 10 days) treatment was combined with mefloquine (20 mg/kg/
      day x 4), 1 of the 2 infected monkeys was cured, while the combination of a
      higher dose of ketoconazole (75 mg/kg/day x 10 days) with mefloquine (20
      mg/kg/day x 4), had a complete curative effect on P. knowlesi infection in all
      the treated monkeys (7/7). Besides exerting direct antimalarial action against a
      mefloquine-resistant P. knowlesi, ketoconazole also acts as an inhibitor of
      hepatic microsomal CYP4503A, which regulates and slows down mefloquine
      biotransformation to carboxymefloquine, resulting in a possible elevation of the
      effective plasma drug level, which seems to be responsible for elimination of the
      resistant P. knowlesi. The study shows a resistance reversal effect of a
      ketoconazole - mefloquine combination that could be exploited for the control of
      mefloquine-resistant malaria infection. The study shows that ketoconazole can
      reverse mefloquine resistance of P. knowlesi. These findings can also be applied
      to reverse mefloquine resistance of P.falciparum in areas where mefloquine
      resistance is already established. The precise role of parasite CYP450 in
      mefloquine resistance and its possible role, if any, in expelling the
      intracellular mefloquine from the resistant plasmodia still remains to be
      elucidated.

PMID- 15991490
TI  - Identification and characterization of cross-reactive antigens from Neospora
      caninum and Toxoplasma gondii.
AB  - Murine monoclonal antibodies (mAbs) against Neospora caninum tachyzoites were
      produced to identify the cross-reactive antigens between N. caninum and
      Toxoplasma gondii. Ten mAbs recognizing cross-reactive antigens of both parasites
      were obtained and tentatively classified into 6 different groups based on their
      reactivity patterns in an indirect fluorescent antibody test and Western blot
      analysis. Three mAbs in group 1 recognized antigens located on the surface of
      parasites with molecular masses ranging from 28 to 76 kDa; one mAb in group 2
      recognized antigens located on interior organelles of parasites with a molecular
      mass of 50 kDa; one mAb in group 3 recognized antigens located on interior
      organelles of parasites with molecular masses of 35 kDa and 14 kDa; three mAbs in
      group 4 recognized antigens located on interior organelles with a molecular mass
      of 64 kDa; one mAb in group 5 recognized antigens located on the surface of
      parasites with an unknown molecular mass; one mAb in group 6 recognized antigens
      located on the apical end of parasites with an unknown molecular mass. The mAbs
      in groups 1, 2, 3, and 5 showed inhibitory effects on the growth of the two
      parasites in vitro in a dose-dependent manner. A cDNA expression library prepared
      from N. caninum tachyzoite mRNA was immunoscreened with the mAb panel. Three
      kinds of proteins, protein disulfide isomerase (PDI), heat-shock protein 70
      (HSP70), and ribosomal protein 1 (RP1), were identified as cross-reactive
      antigens recognized by mAbs in groups 2, 3, and 4, respectively. Some of the
      proteins could be useful in developing vaccines or drugs for controlling the
      diseases caused by the two parasites.

PMID- 15991491
TI  - Host serum modifies the drug susceptibility of Babesia bovis in vitro.
AB  - Babesia parasites generally require a defined percentage of serum in the culture
      medium for their in vitro growth. In this study, we attempted to culture Babesia
      bovis in a serum-free condition. The growth pattern and morphology of B. bovis in
      serum-free (plain) GIT medium were unaltered as compared to those of the standard
      growth condition containing 40% bovine serum in M199. When exposed to the test
      drugs, the parasite in plain GIT medium showed clearly lower IC50 values than
      those in 40% serum-containing G IT medium, indicating that several serum
      components may interfere with the drug bio-availability. Therefore, the serum
      free culture system is useful for standardizing drug test protocols and
      understanding the roles of serum factors in the drug test.

PMID- 15991492
TI  - Detection of species-specific antibody response of humans and mice bitten by sand
      flies.
AB  - Sand fly saliva plays an important role in Leishmania transmission. We
      characterized the host antibody response to saliva from 3 sand fly species.
      Specific IgG was observed in sera from experimentally bitten mice as well as in
      sera from individuals living in the endemic area of Leishmania tropica in
      Sanliurfa, Turkey. Sera of Sanliurfa inhabitants showed high IgG levels against
      saliva of Phlebotomus sergenti and P. papatasi, the 2 most abundant sand fly
      species in this area, but did not react with saliva of the New World sand fly,
      Lutzomyia longipalpis. Patients with active Le. tropica lesions possessed
      significantly higher anti-P. sergenti IgG levels than the healthy individuals
      from the same place while anti-P. papatasi IgG levels were equal in both groups.
      Major protein bands in P. papatasi and P. sergenti saliva reacted with both,
      human and mice sera; in P. papatasi, however, mouse IgG recognized preferentially
      the 42 kDa protein band while the human IgG reacted strongly with the 30 kDa
      band. Our data suggest that the antibody response to sand fly saliva could be
      used for monitoring the exposure of humans and other hosts to sand flies and
      might be used as a marker of risks for Leishmania transmission in endemic areas.

PMID- 15991493
TI  - Different mechanisms of transmission of the microsporidium Octosporea bayeri: a
      cocktail of solutions for the problem of parasite permanence.
AB  - Periods of low host density impose a constraint on parasites with direct
      transmission, challenging their permanence in the system. The microsporidium
      Octosporea bayeri faces such constraint in a metapopulation of its host, the
      cladoceran Daphnia magna, where ponds frequently lose their host population due
      to ponds drying out in summer and freezing in winter. We conducted experiments
      aimed to investigate the mechanisms of transmission of O. bayeri, and discuss how
      these mechanisms could contribute to the parasite's permanence in the system.
      Spores accumulate in the fat cells and the ovaries of the host, and vary in
      morphology, possibly corresponding to 3 different spore types. Horizontal
      transmission occurred through the release of spores from dead hosts, with the
      proportion of infected hosts depending on the spore dose. Further, spores are
      able to persist outside the host both in dry and wet conditions. Vertical
      transmission occurred to both parthenogenetic and sexual offspring. The former
      were invariably infected, while the sexually produced resting eggs (= ephippia)
      had a less efficient transmission. The parasite may be carried by the ephippia,
      and thus disperse to new ponds together with the host. Together, these mechanisms
      may allow the parasite to endure periods of harsh environmental conditions both
      outside and inside the host.

PMID- 15991494
TI  - Description of inflammation and cytokine profile at the inoculation site and in
      heart tissue of mice re-infected with Trypanosoma cruzi vector derived-metacyclic
      trypomastigotes.
AB  - We studied the role of Trypanosoma cruzi reinfection in regard to inflammatory
      and cytokine response at the inoculation site, lymph node and heart. We
      reinfected Balb/c mice intradermically into the hind foot-pad with natural
      infective metacyclic trypomastigotes. They were followed from 24 h to 30 days
      after the last reinfection. At the inoculation site 24 h after the last re
      infection, the infiltrating inflammatory cells increased dramatically with
      respect to baseline inflammation, reaching maximum infiltrates for the third day.
      In contrast, parasite DNA was undetectable 24 h after inoculation, despite poor
      cytokine induction, only IFN-gamma, IL-12 and TGF-beta were noticeable on days 7
      and 15, whereas in the lymph nodes draining the inoculation site positive
      expression of IL-2, IL-4, IL-12 and TGF-beta were found to be induced as soon as
      24 h after re-entry of parasite. In the heart, the inflammatory response
      increased immediately 24 h after re-entry of parasites, reaching its maximum on
      the 7th day and returning to baseline on day 30. In conclusion, although the
      inflammatory response is triggered in both compartments by re-entry of parasites,
      the inflammatory process returns almost to baseline after 30 days, leaving a
      persistent low-grade inflammation.

PMID- 15991495
TI  - Long-lasting effect of stress on susceptibility of a freshwater clam to copepod
      parasitism.
AB  - The question whether a stress event can have a long-lasting effect on
      susceptibility to parasites was studied using a freshwater bivalve clam and its
      crustacean parasite as a model system. Anodonta piscinalis clams were collected
      from 2 populations during August-September 2002. Clams were transported to the
      laboratory and marked. The stressed clams were subjected to low oxygen for 25
      days, while the unstressed control clams were caged in their lakes of origin for
      the same period. Then the clams were transported to a third lake where they were
      exposed to natural infections by the ergasilid copepod, Paraergasilus rylovi, 11
      months after the stress event. The stressed clams were more intensively
      parasitized. They also showed lower growth, lower reproduction and lower survival
      than the unstressed control clams. The results indicate that susceptibility of A.
      piscinalis to P. rylovi infection may be condition dependent, and that stress may
      have a long-lasting, increasing effect on host susceptibility to parasitism in
      natural populations.

PMID- 15991496
TI  - Comparative studies on susceptibilities of two different Japanese isolates of
      Oncomelania nosophora to three strains of Schistosoma japonicum originating from
      Japan, China, and the Philippines.
AB  - Oncomelania nosophora (Gastropoda: Pomatiopsidae) is the intermediate host of
      Schistosoma japonicum in Japan. Although most of the snails were eliminated
      during the 20th century, they are still found in two areas in Japan. One area is
      in the Kofu Basin, including Nirasaki City, in Yamanashi Prefecture. The other is
      the Obitsu River Basin in Kisarazu City, Chiba Prefecture. Snails collected in
      Nirasaki and Kisarazu were exposed to 3 geographical strains of S. japonicum
      originating from Japan, China, and the Philippines. Both isolates of O. nosophora
      showed high susceptibility to the Japanese strain of S. japonicum (74.0% - 82.2%,
      for the Nirasaki isolate and 58.0% - 56.0% for the Kisarazu isolate) and low
      susceptibility to the Chinese strain (0.0% - 1.3% and 1.4% - 7.9% respectively).
      In contrast, the susceptibility of the snails to the Philippine strain was
      significantly different (P < 0.01) between the isolates (3.3% - 6.6% for the
      Nirasaki isolate and 31.9% - 75.9% for the Kisarazu isolate). To examine the
      differences in infectivity in detail, we conducted histological observations of
      snails exposed to the Philippine strain at 3 h, 1, 3, and 15 days after
      miracidial exposure. We found differences in the development of the parasite
      between the isolates of snails from early after exposure.

PMID- 15991497
TI  - An expressed sequence tag survey of gene expression in the pond snail Lymnaea
      stagnalis, an intermediate vector of trematodes [corrected].
AB  - The pond snail Lymnaea stagnalis is an intermediate vector for the liver fluke
      Fasciola hepatica, a common parasite of ruminants and humans. Yet, despite being
      a disease of medical and economic importance, as well as a potentially useful
      comparative tool, the genetics of the relationship between Lymnaea and Fasciola
      has barely been investigated. As a complement to forthcoming F. hepatica
      expressed sequence tags (ESTs), we generated 1320 ESTs from L. stagnalis central
      nervous system (CNS) libraries. We estimate that these sequences derive from 771
      different genes, of which 374 showed significant similarity to proteins in public
      databases, and 169 were similar to ESTs from the snail vector Biomphalaria
      glabrata. These L. stagnalis ESTs will provide insight into the function of the
      snail CNS, as well as the molecular components of behaviour and response to
      parasitism. In the future, the comparative analysis of Lymnaea/Fasciola with
      Biomphalaria/Schistosoma will help to understand both conserved and divergent
      aspects of the host-parasite relationship. The L. stagnalis ESTs will also assist
      gene prediction in the forthcoming B. glabrata genome sequence. The dataset is
      available for searching on the world-wide web at
      http://zeldia.cap.ed.ac.uk/mollusca.html.

PMID- 15991498
TI  - An evaluation of serial analysis of gene expression (SAGE) in the parasitic
      nematode, Haemonchus contortus.
AB  - This study evaluated a relatively new molecular technique, serial analysis of
      gene expression (SAGE), as a tool for quantifying gene expression in the ovine
      abomasal nematode Haemonchus contortus for which there is relatively limited
      (approximately 20% gene coverage) sequence information. SAGE technology generates
      data that are both qualitative and quantitative and, as such, compliments other
      functional genomics approaches such as EST analysis and micro-array. Prior to
      embarking on large-scale comparisons, the present study was initiated to
      establish (i) how well SAGE and EST data taken from the same life-cycle stage
      would compare, (ii) how easily SAGE tags could be assigned to genes given that
      the genome sequence is not available and (iii) whether it would be possible to
      extend the sequences of the SAGE tags to facilitate their identification. Of 2825
      tag sequences analysed from adults harvested 28 days post-infection, the identity
      of the encoding gene could be ascribed to 63% of the tags. The relative abundance
      of these genes, arbitrarily categorized on the basis of function, was comparable
      with that of an EST dataset also from adults (n = 2317). In addition, tag
      sequences could be readily extended and thereby identified using a tag-based
      primer and Reverse Transcription-PCR.

PMID- 15991499
TI  - A spectrum of functional genes mobilized after Trichinella spiralis infection in
      skeletal muscle.
AB  - Trichinella spiralis infection causes the transformation of infected muscle
      cells, which leads to nurse cell formation. To search for the candidate genes
      responsible for nurse cell formation, cDNA microarray analysis of muscle tissues
      was performed before and after Trichinella infection. The Atlas mouse 1.2 cDNA
      expression microarray revealed the expression profiles of 1176 known genes. Out
      of these, 311 gene expressions were detected in normal and/or infected muscles.
      After the infection, 184 out of the 311 genes increased in expression by more
      than 3-fold. These included genes responsible for cell differentiation,
      proliferation, cell cycle and apoptosis. Thus this study suggested candidate
      genes for further investigation to dissect the molecular mechanisms of nurse cell
      formation.

PMID- 15991500
TI  - Immune modulation by a high molecular weight fraction from the rat tapeworm
      Hymenolepis diminuta.
AB  - The host-parasite relationship is exquisitely specific. In exploiting the host
      niche, a variety of helminth parasites have been shown to directly manipulate
      their hosts' immune responses. We assessed the ability of a whole-worm extract of
      Hymenolepis diminuta to modulate immune cell activation. Immune cells isolated
      from human blood or rodent spleens were activated with the T cell mitogen,
      concanavalin A (Con A) +/- H. diminuta extract and cytokine production (i.e. IL
      2, -4, -10, -12) and proliferation assessed by ELISA and [3H]thymidine
      incorporation 24 and 72 h post-treatment, respectively. Co-treatment with the H.
      diminuta extract (100 microg protein/ml) virtually abolished Con A-induced immune
      cell proliferation, which was not due to increased apoptosis. Boiling of the worm
      extract reduced its anti-proliferative effect and fractionation indicated that a
      > 50 kDa component was predominantly responsible for the inhibition of Con A
      induced immune cell proliferation. Cytokine determinations revealed that the H.
      diminuta extract significantly reduced Con A-stimulated IL-2 and IL-4, but
      enhanced the production of IFNy, IL-12 and IL-10. The increased IL-12 was due to
      an LPS contaminant in the extract and a helminth-derived 'IL-12'-like peptide
      that bound in the ELISA and Western blots. In contrast, a H. diminuta-derived
      factor directly stimulated IL-10 production by murine splenocytes, and
      contaminating LPS synergistically enhanced the production of IL-10. Thus, H.
      diminuta has the potential to block stimulated T cell proliferation and, by
      inhibiting IL-4 and promoting IL-10 production, may bias the immune environment
      towards one of immunoregulation and away from IL-4 dominated T helper 2 type
      events.

PMID- 15991501
TI  - Flagging the pain: preventing the burden of chronic pain by identifying and
      treating risk factors in acute pain.
AB  - Chronic pain represents a major public health problem that impacts negatively on
      quality-of-life issues and healthcare costs. Unrelieved acute post-traumatic and
      postoperative pains are risk factors in the development of chronic pain, although
      psychological and environmental factors are at work as well. Flagging pain (blue,
      yellow and red flags) helps to identify risk factors in acute pain that need
      attention to avoid the transition from acute postoperative pain to acute
      persistent and then on to chronic pain. This offers a unique opportunity for
      preventative medicine.

PMID- 15991502
TI  - Visual experiences during cataract surgery: what anaesthesia providers should
      know.
AB  - Recently published literature shows that most patients experience a variety of
      visual sensations during cataract surgery under local anaesthesia. Most patients
      (80-100%) retain at least some light perception in the operated eye and many also
      experience a variety of other visual sensations during cataract surgery under
      regional ophthalmic anaesthesia (retrobulbar, peribulbar and sub-Tenon's blocks)
      or topical anaesthesia. The visual sensations experienced include perception of
      movements, flashes, colours, changes in brightness, or the sight of surgical
      instruments, the surgeon's hands or fingers, or even the surgeon. These findings
      are clinically significant because 3-16.2% of patients who had cataract surgery
      under either regional or topical anaesthesia were frightened by their
      intraoperative visual experience. Fear and anxiety may cause some patients to
      become uncooperative during the surgery and may also induce a sympathetic stress
      response that might cause hypertension, tachycardia with myocardial ischaemia,
      hyperventilation or an acute panic attack. These effects are especially
      undesirable as the majority of cataract patients are elderly and have concurrent
      medical problems. Besides increasing the risk of intraoperative complications, a
      frightening visual experience may decrease patient satisfaction. Appropriate
      preoperative counselling has been shown to be effective in reducing the patients'
      fear. As most patients retain some visual function during cataract surgery under
      local anaesthesia, anaesthesia providers should be mindful of this phenomenon and
      offer appropriate preoperative information and counselling to their patients.

PMID- 15991503
TI  - The cardiovascular effects of inspired oxygen fraction in anaesthetized patients.
AB  - BACKGROUND AND OBJECTIVE: Increased inspired oxygen fractions (FiO2) have
      significant haemodynamic effects in awake volunteers. We sought to establish
      whether these effects are also present in anaesthetized patients. METHODS: We
      prospectively studied 30 ASA I-II patients, 15 in each of a propofol and
      sevoflurane group. Their haemodynamic responses, awake and anaesthetized, when
      the FiO2 was changed between 0.3 and 1.0 were measured with a non-invasive
      transthoracic bio-impedance monitor. RESULTS: While preoxygenating awake patients
      in both groups the FiO2 was increased from 0.21 to 1.0. This reduced the mean
      cardiac index (3.38 +/- 0.5 to 3.03 +/- 0.5 L min(-1) m(-2); P < 0.001); reduced
      the heart rate (HR) (68.1 +/- 10.4 to 62.8 +/- 9.4 beats per minute (bpm); P <
      0.001); and reduced the stroke index (50.4 +/- 9.6 to 48.5 +/- 8.6; P = 0.02). It
      increased the systemic vascular resistance index (2060 +/- 319 to 2220 +/- 382
      dyn s(-1) cm(-5) m(-2); P = 0.002); but did not change mean arterial pressure. In
      the anaesthetized patients, when decreasing the FiO2 from 1.0 to 0.3, mean
      cardiac index (L min(-1) m(-2) increased (3.06 +/- 0.57 to 3.25 +/- 0.56, P =
      0.008 for sevoflurane; 2.76 +/- 0.46 to 2.89 +/- 0.42, P = 0.002 for propofol).
      The mean HR (bpm) increased (65.1 +/- 7.8 to 69.1 +/- 7.5, P < 0.001 for
      sevoflurane; 67.5 +/- 11.8 to 72.7 +/- 11.6, P = 0.001 for propofol). The mean
      systemic vascular resistance (dyn s(-1) cm(-5) m(-2)) decreased (1883 +/- 329 to
      1735 +/- 388, P = 0.008 for sevoflurane; 2015 +/- 369 to 1771 +/- 259, P = 0.003
      for propofol). Mean arterial pressure (mmHg) decreased (74.8 +/- 8.7 to 71.4 +/-
      8.7, P < 0.001 for sevoflurane; 72.1 +/- 8 to 66.5 +/- 6.8, P = 0.002 for
      propofol). CONCLUSION: O2 has haemodynamic effects in awake and anaesthetized
      patients. These effects were of overall similar magnitude for patients
      anaesthetized with propofol and sevoflurane.

PMID- 15991504
TI  - Low-dose ketamine failed to spare morphine after a remifentanil-based anaesthesia
      for ear, nose and throat surgery.
AB  - BACKGROUND: Ketamine has been claimed to prevent acute opioid tolerance and
      hyperalgesia following acute exposure to opioids and its use has been proposed to
      decrease postoperative morphine consumption. METHODS: We conducted a randomized,
      double-blind, controlled study to evaluate the effect of intravenous (i.v.)
      ketamine on postoperative pain for 48 h after major ear, nose and throat (ENT)
      surgery. Thirty-one patients received i.v. ketamine 0.15 mg kg(-1) before
      induction and 2 microg kg(-1) min(-1) during anaesthesia, and 31 patients were
      administered placebo in a similar manner. Anaesthesia was standardized with
      remifentanil and propofol, but without nitrous oxide. Standardized postoperative
      analgesia included paracetamol, methylprednisolone and morphine administered via
      a patient controlled analgesia (PCA) device. RESULTS: Intra-operative
      remifentanil consumption was not different between the ketamine group (0.25 +/-
      0.07 microg kg(-1) min(-1)) and the control group (0.22 +/- 0.07 microg kg(-1)
      min(-1)). In the postoperative period, both groups experienced an identical pain
      course evolution. Cumulative morphine consumption was not significantly different
      between groups: at 24 h it was 33.3 +/- 14.9 with ketamine and 31.9 +/- 15.3 mg
      in controls, at 48h it was 40.4 +/- 20.6 mg with ketamine and 42.5 +/- 25.9 mg in
      controls. CONCLUSION: Low-dose ketamine added to a remifentanil-based propofol
      anaesthesia did not reduce morphine consumption after major ENT surgery.

PMID- 15991505
TI  - The effect of adding nitrous oxide on MAC of sevoflurane combined with two target
      controlled concentrations of remifentanil in women.
AB  - BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized, double-blind
      study was to determine the effects of adding nitrous oxide on sevoflurane
      requirement for blunting sympathetic responses after surgical incision combined
      with two different target-controlled concentrations of remifentanil (1 and 3 ng
      mL(-1)) in female. METHODS: 102 female patients, aged 20-50 yr, ASA I, undergoing
      general anaesthesia for elective abdominal surgery were enrolled and randomly
      allocated to receive sevoflurane anaesthesia alone (Group A, n=53), or with the
      addition of 60% nitrous oxide (Group N, n=49). Patients of both groups were
      further assigned to receive a target-controlled remifentanil infusion with an
      effect-site concentration of either 1 ng mL(-1) (Group N1, n=27; Group A1, n=30),
      or 3 ng mL(-1) (Group N3, n=22; Group A3, n=23). Sympathetic responses to
      surgical incision were determined after a 20-min period of stable end-tidal
      sevoflurane and target-controlled remifentanil concentrations. Predetermined end
      tidal sevoflurane concentrations and minimum alveolar concentration (MAC) for
      each group were determined using an up-and-down sequential allocation technique.
      RESULTS: The MAC of sevoflurane was 3.96% (95% confidence interval, CI95: 3.69
      4.23%) in Group A1 and 1.2% (CI95: 0.9-1.3%) in Group N1 (P < 0.01), while in
      Groups A3 and N3 the MAC of sevoflurane was 0.36% (CI95: 0.24-0.47%) and 0.18%
      (CI95: 0.1-0.3%), respectively (P < 0.05). CONCLUSION: Adding 60% nitrous oxide
      reduces the MAC of sevoflurane by 70% when using a remifentanil concentration of
      1 ng mL(-1) and 50% when using a remifentanil concentration of 3 ng mL(-1).

PMID- 15991506
TI  - Postoperative condition after the use of remifentanil with a small dose of
      piritramide compared with a fentanyl-based protocol in patients undergoing
      craniotomy.
AB  - BACKGROUND AND OBJECTIVE: The use of remifentanil requires other analgesics for
      postoperative pain relief compared to fentanyl in patients undergoing craniotomy.
      This could possibly reduce the postoperative advantages of this short-acting
      opioid. METHODS: We compared remifentanil and fentanyl-based anaesthesia in a
      randomized observer and patient blinded trial on patients, undergoing an elective
      craniotomy. Twenty patients received anaesthesia using remifentanil with a small
      dose of piritramide (0.1 mg kg(-1)) after closure of the dura mater. Twenty
      patients underwent a fentanyl-based protocol. In both groups, anaesthesia was
      induced with thiopental and rocuronium, and maintained with 0.6-1 minimum
      alveolar concentration (MAC) isoflurane in a nitrous oxide/oxygen mixture 2:1 and
      rocuronium. Patients received 1 g of paracetamol rectally postoperatively. A
      visual analogue scale (VAS) for pain, the Glasgow Coma Score, a modified Aldrete
      Score, arterial carbon dioxide tension (PaCO2) and piritramide consumption were
      evaluated every half an hour postoperatively. RESULTS: No significant differences
      were found for pain, Aldrete or Glasgow Coma scores or for PaCO2 between the
      groups when controlled for age, although the pain and Glasgow Coma Scores were
      consistently higher and PaCO2 lower in the remifentanil group. Furthermore, 11
      out of 20 patients in the remifentanil group requested extra piritramide as
      opposed to 7 out of 20 in the fentanyl group (P = 0.11). CONCLUSIONS: Despite the
      intraoperative use of piritramide in the remifentanil group, patients experienced
      more pain postoperatively. A significant influence of age on pain intensity was
      found. The use of remifentanil with a small dose of piritramide of 0.1 mg kg(-1)
      has no evident advantage over the use of fentanyl considering the postoperative
      conditions after craniotomy.

PMID- 15991507
TI  - Evaluation of a local anaesthesia regimen using a subphrenic catheter after
      gynaecological laparoscopy.
AB  - BACKGROUND AND OBJECTIVE: The purpose of intraperitoneal local anaesthetic
      administration is to block visceral nociceptive conduction and to provide an
      additional route of analgesia. The present study evaluates the effects of
      sequential injections of bupivacaine on postoperative pain through a subphrenic
      catheter. METHODS: In this double-blinded controlled study, patients scheduled
      for gynaecological laparoscopy were randomly divided into two groups. One group
      received 20 mL of saline with 1:200000 epinephrine through a subphrenic catheter
      before the incision closure and at 4-hourly intervals for the first postoperative
      20 h. The second group received 20 mL of bupivacaine 0.125% with 1:200000
      epinephrine at the same injection times. Postoperative pain scores and
      consumption of analgesics were compared. RESULTS: There were no statistical
      differences in pain scores at rest or incidence of shoulder pain between the two
      groups, but the patients of the bupivacaine group reported lower pain scores on
      coughing only in the first hour postoperatively (P = 0.007). Although the
      patients consumed comparable amounts of metamizole and ondansetron, the number of
      patients requiring supplemental meperidine and flurbiprofen in the bupivacaine
      group were significantly lower than in the saline group (P < 0.05). CONCLUSIONS:
      This study demonstrates that intraperitoneal bupivacaine may reduce pain on
      coughing in the early postoperative period and the consumption of analgesics
      postoperatively. The subphrenic catheter technique had no impact upon pain at
      rest and shoulder-tip pain after gynaecological laparoscopy.

PMID- 15991508
TI  - Addition of dexmedetomidine to lidocaine for intravenous regional anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine the duration of
      onset and regression time of sensory and motor blocks, the quality of anaesthesia
      and postoperative analgesia by the addition of dexmedetomidine to local
      anaesthetic solution in intravenous regional anaesthesia (IVRA). METHODS: Forty
      patients scheduled for elective hand surgery participated in this prospective
      randomized double-blind study. The IVRA was achieved using 3 mg kg(-1) lidocaine
      diluted with saline to a total volume of 40 mL in the control group or 1 microg
      kg(-1) of dexmedetomidine + 3 mg kg(-1) lidocaine diluted with saline to a total
      volume of 40 mL in the dexmedetomidine group. The onset and regression times for
      sensory and motor blocks were recorded. Qualities of anaesthesia, intraoperative
      and postoperative analgesic requirements were noted. RESULTS: There was no
      difference between the groups with respect to sensory and motor blocks onset and
      regression time. The quality of anaesthesia was better in the dexmedetomidine
      group than the control group and the difference was statistically significant.
      Intraoperative and postoperative analgesic requirements were greater in the
      control group than in the dexmedetomidine group. CONCLUSIONS: Addition of
      dexmedetomidine to local anaesthetic solution in IVRA improved the quality of
      anaesthesia and decreased analgesic requirements, but had no effect on the
      sensory and motor blocks onset and regression times.

PMID- 15991509
TI  - Sciatic nerve block with 0.5% levobupivacaine, 0.75% levobupivacaine or 0.75%
      ropivacaine: a double-blind, randomized comparison.
AB  - BACKGROUND AND OBJECTIVE: This prospective, randomized, double-blind study was
      conducted to evaluate the onset time and duration of sciatic nerve block produced
      with 0.5% levobupivacaine, 0.75% levobupivacaine and 0.75% ropivacaine. METHODS:
      Forty-five healthy patients undergoing hallux valgus repair were randomly
      allocated to receive sciatic nerve block with levobupivacaine 0.5% (n=15),
      levobupivacaine 0.75% (n=15) or ropivacaine 0.75% 20 mL (n=15). A femoral nerve
      block was also performed with mepivacaine 2% 15 mL to cover pain related to the
      thigh tourniquet. A blinded observer recorded the onset time and duration of
      sciatic nerve block. RESULTS: The median (range) onset time was 5 (5-40) min with
      0.75% levobupivacaine, 30 (5-60) min with 0.5% levobupivacaine and 20 (5-50) min
      with 0.75% ropivacaine (P = 0.02 and P = 0.12, respectively). Mean (25-75
      percentiles) first request for pain medication occurred after 13 (11-14) h with
      0.75% ropivacaine, 18 (15-19) h with 0.75% levobupivacaine and 16 (13-20) h with
      0.5% levobupivacaine (P = 0.002 and P = 0.002, respectively). Rescue tramadol
      after surgery was required by three patients in the 0.75% levobupivacaine group,
      eight patients in the 0.5% levobupivacaine group and nine patients in the 0.75%
      ropivacaine group (P = 0.05). CONCLUSIONS: We conclude that 0.75% levobupivacaine
      provides a shorter onset time than 0.5% levobupivacaine and a longer duration of
      postoperative analgesia than both 0.5% levobupivacaine and 0.75% ropivacaine with
      reduced need for rescue analgesia after surgery.

PMID- 15991510
TI  - Effects of hyperbaric spinal ropivacaine for caesarean section: with or without
      fentanyl.
AB  - BACKGROUND AND OBJECTIVE: Adding various opioids to the local anaesthetic
      solution administrated intrathecally improves the analgesic potency of spinal
      analgesia. The purpose of this study was to evaluate the efficacy and safety of
      intrathecal fentanyl 10 microg added to 15 mg hyperbaric ropivacaine in patients
      undergoing caesarean section under spinal anaesthesia. METHODS: Thirty-seven
      healthy, full-term parturients were randomly assigned into two groups: Group S
      (saline group, n=17) received 15 mg hyperbaric ropivacaine in 2.5 mL + 0.5 mL
      saline; Group F (fentanyl group, n=20) received 15 mg hyperbaric ropivacaine in
      2.5 mL + 10 microg fentanyl in 0.5 mL, intrathecally. Characteristics of spinal
      block, intraoperative quality of spinal anaesthesia, time to first feeling of
      pain (complete analgesia), time to first request of analgesics postoperatively
      (effective analgesia), side-effects and fetal outcomes were evaluated. RESULTS:
      Regression of sensory block to L5 was significantly prolonged in the fentanyl
      group compared with the saline group (P = 0.001). Time to the first feeling of
      pain (130.6 +/- 15.8 min vs. 154.3 +/- 31.1 min; P = 0.008) and the first
      analgesic requirement (161.2 +/- 32.6 min vs. 213.0 +/- 29.3 min; P < 0.001) were
      significantly shorter in the saline group compared with the fentanyl group. Side
      effects, umbilical arterial and venous blood gases did not differ between the
      groups. Apgar scores were similar in both groups and no infants had an Apgar
      score < or =7 at 5 min. CONCLUSIONS: The addition of fentanyl 10 microg, to
      hyperbaric ropivacaine 15 mg, for spinal anaesthesia increased the duration of
      analgesia in the early postoperative period in patients undergoing caesarean
      delivery.

PMID- 15991511
TI  - Plasma levels of IL-10 and nitric oxide under two different anaesthesia regimens.
AB  - BACKGROUND AND OBJECTIVE: An alteration in production of both interleukin-10 (IL
      10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma.
      It is also suggested that IL-10 could be an important factor in regulating NO
      metabolism during the postoperative period. Furthermore, NO seems to play a
      crucial role in the anaesthetic state. The purpose of this study was to
      investigate plasma levels of IL-10 and NO following surgery, any possible
      correlation between these two variables and whether anaesthesia technique could
      influence NO and IL-10 circulating concentrations. METHODS: Thirty-two patients
      scheduled to undergo elective major surgery were enrolled in the study and
      allocated into two groups to receive two different techniques of anaesthesia,
      total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia
      (Group II). Blood samples were drawn before (t0), at the end (t1) of operation
      and after 24 h (t2). Plasma IL-10 and NO levels were measured by using an enzyme
      linked-immunosorbent assay (ELISA) and a total NO assay kit, respectively.
      RESULTS: In both patient groups there was a significant decrease of plasma NO
      levels at the end of surgery (30.35 +/- 2.70 mmol L(-1) at t0 to 13.76 +/- 1.51
      mmol L(-1) at t1 in Group I, P < 0.0001; 28.23 +/- 2.50 mmol L(-1) at t0 to 11.38
      +/- 0.95 mmol L(-1) at t1 in Group II, P < 0.0001). This reduction remained at 24
      h postoperatively (14.33 +/- 1.52 mmol L(-1) in Group I, P < 0.0001; 12.52 +/-
      1.11 mmol L(-1) in Group II, P < 0.0001, both vs. t0). There was an increase in
      IL-10 concentrations (26.35 +/- 3.42 pg mL(-1) and 75.39 +/- 8.33 pg mL(-1) at t1
      and t2, respectively, vs. 4.93 +/- 0.31 pg mL(-1) at t0, P = 0.03 and P < 0.0001,
      respectively, in Group I; 26.18 +/- 3.22 pg mL(-1) and 69.91 +/- 7.33 pg mL(-1)
      at t1 and t2, respectively, vs. 5.50 +/- 0.33 pg mL(-1) at t0, P = 0.02 and P <
      0.0001, respectively, in Group II). No relationship was found between circulating
      IL-10 and NO. CONCLUSIONS: During the postoperative period, IL-10 overproduction
      does not correlate with the decrease in systemic NO concentration.

PMID- 15991512
TI  - Effects of propofol on N-methyl-D-aspartate receptor-mediated calcium increase in
      cultured rat cerebrocortical neurons.
AB  - BACKGROUND AND OBJECTIVE: The intravenous anaesthetic propofol has been reported
      to exert neuroprotective actions by several mechanisms. This study has been
      designed to investigate the effects of propofol on intracellular calcium increase
      in cultured cerebrocortical neurons after exposure to pathological concentrations
      of N-methyl-D-aspartate (NMDA) mediated by potential direct interactions of
      propofol with NMDA receptors. METHODS: The effects of propofol (0.1-100 micromol)
      on intracellular calcium increase induced by 300 micromol NMDA (180 s) were
      measured in cultured cerebrocortical neurons using the calcium-sensitive
      fluorochrome calcium green-5N-acetoxymethylester with confocal laser scanning
      microscopy. RESULTS: The intraneuronal calcium increase after exposure to 300
      micromol NMDA depended on extracellular calcium concentration. Propofol reduced
      the increase of NMDA receptor-induced intraneuronal calcium concentration
      dependently with a threshold concentration for a significant effect of 10
      micromol. The overall effect was small, since even high concentrations of
      propofol (100 micromol) diminished intraneuronal calcium rise by only 50%.
      CONCLUSIONS: The threshold concentration for significant effects of propofol on
      the NMDA-induced increase of intraneuronal calcium turned out to be in the upper
      limit of propofol concentrations that are considered to be clinically relevant.
      However, in the presence of high propofol concentrations, inhibition of NMDA
      receptor-mediated calcium increase might contribute to neuroprotective effects
      observed with propofol.

PMID- 15991513
TI  - Use of epidural blockade in a patient with hip fracture and aortic stenosis.

PMID- 15991514
TI  - Brachial plexus block with ropivacaine and bupivacaine for the formation of
      arteriovenous fistula in patients with end-stage renal failure.

PMID- 15991515
TI  - Interference of patent blue V dye with pulse oximetry and co-oximetry.

PMID- 15991516
TI  - Recurrent asystole during electrocauterization: an uncommon hazard in common
      situations.

PMID- 15991517
TI  - Minimum inspired oxygen concentration alarm: do we go too low?

PMID- 15991518
TI  - Peripheral blocks of trigeminal nerve for facial soft-tissue surgery: learning
      from failures.

PMID- 15991519
TI  - General and subarachnoid anaesthesia in a patient with acquired C1 esterase
      inhibitor deficiency.

PMID- 15991520
TI  - The potential and problems of screening for ovarian cancer.
AB  - Screening for ovarian cancer using tumor markers is simple but often associated
      with an increased rate of false negatives and a low rate of detection of early
      stage cancers. The transvaginal ultrasonic method, on the other hand, detects an
      increased number of Stage I cancers (about 70% of the total cancers detected),
      but it takes time. Our method is performed in a short time and is most suitable
      as a screening method. Although there is no established assessment of ovarian
      cancer screening, we have outlined the potential and the problems associated with
      it based on the reports published to date and the results of our study.

PMID- 15991521
TI  - Management of endometrial carcinoma with cervical involvement. An unsettled
      issue.
AB  - The purpose of the present report is to review the various management options of
      endometrial carcinoma with cervical involvement. A Medline literature search for
      publications dealing with endometrial carcinoma (EC) with cervical involvement
      and treatment was made. Although many publications deal with EC with cervical
      involvement there is a lack of prospective controlled trials. Only one
      prospective randomized phase III trial has been published. The inaccuracies of
      clinical staging, the scarcity of reports with surgically staged patients, the
      multiple types of cervical involvement and prognostic indicators and the
      remarkable variations in treatment render it difficult to compare outcome results
      between publications. The small number of patients in many of these studies and
      their retrospective uncontrolled nature add to this difficulty. There are
      conflicting reports with regard to factors affecting outcome, also complicating
      the management issue of endometrial carcinoma with cervical involvement and
      comparison of treatment results. The optimal management of EC with cervical
      involvement remains to be established.

PMID- 15991522
TI  - Tamoxifen and endometrial cancer. Is screening necessary? A review of the
      literature.
AB  - Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti
      oestrogenic activity in the breast and oestrogenic effects in various tissues
      such as the endometrium, bone and cardiovascular territory. As adjuvant hormone
      therapy, it has a clear beneficial effect in patients with breast cancer,
      reducing relapses, contralateral breast cancer and mortality. Its most important
      secondary effect is a greater rate of occurrence of endometrial cancer. Although
      the risk/benefit ratio is clearly positive, the follow-up on these patients is
      still an issue. In women with metrorrhagia, it is clear that an endometrial
      sample must be obtained for histological examination and the best procedure today
      is hysteroscopic-directed biopsy. Nevertheless, the need to screen asymptomatic
      patients is not universally accepted. The vaginal ultrasound scan gives a great
      number of false positives. This entails more aggressive and more expensive
      procedures such as hysteroscopic-directed biopsy, meaning greater expense and
      more complications. As a result, the cost/benefit ratio is not very favourable.
      The rate of occurrence of endometrial cancer in 1026 tamoxifen-treated patients
      with breast cancer in our hospital between 1999 and 2001 was 1.25%. Two cases
      were diagnosed in asymptomatic patients. In this article, we analyse the
      literature on the need to screen patients on tamoxifen and about the most
      appropriate diagnostic protocol.

PMID- 15991523
TI  - Accuracy of ovarian cancer ICD-10 diagnosis in a Danish population-based hospital
      discharge registry.
AB  - OBJECTIVE: We estimated the accuracy of ICD-10 diagnosis of ovarian cancer in a
      Danish discharge registry (HDR) by comparing it with Cancer Registry data (DCR).
      STUDY DESIGN AND SETTING: Patients (N=489) living in North Jutland County,
      Denmark with ovarian cancer or borderline tumour registered in the HDR or the
      DCR. We estimated the completeness and positive predictive value (PPV) of ovarian
      cancer discharge diagnosis. Mortality rates were constructed for both registries.
      RESULTS: The completeness in the HDR for ovarian cancer was 96% (95% confidence
      interval [CI]: 94%-98%) and PPV was 87% (95% CI: 85%-90%). 87 (18%) of the
      patients coded with ovarian cancer in the HDR had borderline tumours. When
      borderline tumours were excluded from the DCR, the PPV declined to 69% and the
      completeness did not change. The mortality rate ratio for ovarian cancer
      registered in the HDR compared to the DCR was 1.08 (95% CI: 0.90-1.29).
      CONCLUSION: The discharge data (ICD-10) had some misclassification, but can be a
      valuable tool in assessment of the prognosis of ovarian cancer.

PMID- 15991524
TI  - Expression of cyclooxygenase-2 in endometrial adenocarcinoma.
AB  - Studies have shown that COX-2 is up-regulated in several epithelial carcinomas.
      In this study, we wish to elucidate if endometrial cyclooxygenase-2 (COX-2)
      expression in endometrial adenocarcinoma is increased relative to normal
      endometrium. Thirty-six deparaffinized tissue sections from patients with
      endometrial adenocarcinoma were analyzed by immunohistochemistry for the presence
      of COX-2. A control group consisted of 13 age-matched patients without
      malignancy, who underwent surgery for uterine prolapse. Statistical analysis was
      performed using the Kruskal-Wallis test; differences between groups were
      evaluated using the Fisher's Exact Test. We found that COX-2 expression was
      markedly increased in 13 of 36 patients (36.1%) with endometrial adenocarcinoma:
      in contrast only one of 13 (7.7%) control patients demonstrated increased COX-2
      expression (p < or = 0.05). Eight of the 13 COX-2 positive patients in the study
      had well differentiated adenocarcinoma; the remaining five COX-2 positive
      patients had moderately and poorly differentiated adenocarcinoma (4 and 1,
      respectively). In conclusion, COX-2 expression in the endometrium is associated
      with endometrial adenocarcinoma, especially of the well differentiated type. This
      may provide an avenue for chemoprevention of endometrial adenocarcinoma. In
      addition, with new selective inhibitory drugs being developed, inhibition of COX
      2 may play an adjunctive role approach to standard therapy, especially for well
      differentiated endometrial carcinoma. Further studies are required to investigate
      the role of COX-2 expression in carcinogenesis.

PMID- 15991525
TI  - Doxorubicin and ifosfamide-mesna in advanced and recurrent uterine sarcomas.
AB  - PURPOSE OF INVESTIGATION: To report the experience of a single institution in the
      south of Israel with doxorubicin and ifosfamide-mesna in patients with
      advanced/recurrent uterine sarcomas. METHODS: The hospital records of five
      patients with advanced/recurrent uterine sarcomas who had combination
      chemotherapy with doxorubicin and ifosfamide-mesna were retrospectively reviewed.
      Doxorubicin 30 mg/m2 was given on days 1 and 2 and ifosfamide 2000 mg/m2 (+
      mesna, W/W 60%) was given on days 1, 2 and 3 of every 21 days. Dose intensity,
      relative dose intensity and average relative dose intensity (ARDI) of
      chemotherapy were calculated. Response was determined using clinical evaluation
      and radiological reports. Toxicity was graded using the National Cancer Institute
      (NCI) criteria. RESULTS: The median ARDI of the combination of doxorubicin and
      ifosfamide received by the patients was 0.68 (range, 0.53-0.74). One (20%)
      patient had disease complete response lasting three months and four (80%)
      patients had progressive disease. Toxicity was mainly hematological with grade 3
      or 4 leukopenia--four (80%) patients, neutropenia--four (80%), thrombocytopenia-
      one (20%) and anemia--one (20%). Non-hematological toxicity was negligible. At
      follow-up, four (80%) patients had died of disease and one (20%) was alive with
      disease. CONCLUSION: Although the combination of doxorubicin and ifosfamide has
      certain activity in advanced/recurrent uterine sarcomas, the toxicity is of much
      concern and the results of treatment in terms of response duration and survival
      are poor.

PMID- 15991526
TI  - Color Doppler assessment of blood flow in endometrial cancer.
AB  - OBJECTIVE: To determine the location and intensity of angiogenesis as well as
      selected flow parameters by transvaginal color Doppler (TVCD) and to evaluate the
      relation of myometrial invasion, histological grading, lymph nodes, and omental
      and adnexal metastasis on blood flow characteristics in endometrial cancer.
      METHODS: Transvaginal colour Doppler and pulsed Doppler ultrasound were performed
      on 90 women with endometrial cancer. The degree of invasion as well as adnexal,
      omental, and pelvic lymph node metastasis was evaluated. Location of the blood
      vessels (peripheral, central, mixed) and vascular density as well as selected
      Doppler blood flow indices: PSV, RI of neoplastic infiltration was assessed.
      RESULTS: The median age of the 90 women was 63.3 +/- 12.3 years (range 32 to 86
      years); of these 92.2% were postmenopausal. Cancer concerned only the endometrium
      (E), with superficial (S) and deep infiltration (D) established in 14.4%, 45.6%
      and 40%, respectively. The histological maturity was as follows: G1 - 17.6%, G2 -
      66.7%, G3 - 16.6% of cases. Adnexal, omental and lymph node metastasis was found
      in 12.2%, 3.3% and 16.6%, respectively. Abnormal low impedance and high velocity
      flow (mean RI 0.38 +/- 0.09, PSV 20.45 +/- 9.6 cm/sec) were found in 88.9% of
      cases. In types E, S, D in 61.5%, 92.7% and 94.4%, respectively (p = 0.003).
      Differences in RI and PSV between groups with high and low vascular density were
      statistically significant (p = 0.005 and 0.001, respectively). In all cases
      peripheral and mixed vascularity were found more frequently (p < 0.05). A
      positive significant correlation between vascular density increase and
      surgicopathological stage of cancer was found more frequently (p < 0.005). There
      were significant differences in vascular density, Doppler blood flow indices and
      vascular location in each type of histological malignancy (p < 0.05). No
      significant differences in each flow parameter in hematogenous-adnexal/omental
      metastatic and non metastatic cases were found, whereas pelvic lymph node
      involvement and vascular density were shown to be statistically significant (p <
      0.02). There were significant differences in vascular density in lymph-node
      positive cases whereas the remaining flow parameters did not differ. CONCLUSIONS:
      These results suggest that TVCD evaluation of endometrial cancer is a reliable
      method for assessing endometrial angiogenesis. Our results indicate that blood
      flow rates correspond with increased angiogenesis in endometrial cancers, and
      might potentially be used as a good prediction factor for tumor progression and
      metastasis in affected women. Preoperative ultrasound examination should be seen
      as an important tool in the establishment of individualized treatment programs
      for women with endometrial cancer.

PMID- 15991527
TI  - Comparative evaluation of standard criteria and CA-125 in ovarian cancers treated
      with platinum or paclitaxel.
AB  - PURPOSE: To assess CA-125 in defining tumor response in patients treated with
      paclitaxel. PATIENTS AND METHODS: We analyzed 150 women treated for epithelial
      ovarian carcinoma with platinum or paclitaxel. We compared the patients treated
      with two agents, using a precise definition of CA-125 response, determined by 50%
      and 75% reductions, like other authors have published. RESULTS: CA-125 criteria
      gave response rates very similar to the standard response rates, both for
      patients treated with platinum (75% vs 63%) and also for those treated with
      paclitaxel (40% vs 39%). Rates of false-positive prediction of response by CA-125
      were also similar for patients treated with these two agents. CONCLUSION: Precise
      50% or 75% CA-125 response criteria are as sensitive as standard criteria for
      assessing activity of therapy for the ovarian cancers treated with platinum or
      paclitaxel. We propose that they may be useful in defining response in lieu of or
      in addition to standard response criteria in clinical trials involving epithelial
      ovarian cancer.

PMID- 15991528
TI  - Endometrial stromal sarcoma--observational evidence of a genetic background?
AB  - BACKGROUND: Endometrial stromal sarcomas (ESS) constitute only 0.2% of all
      gynecological malignancies, and risk factors or genetic associations are largely
      unknown. We are in contact with more than 100 patients with ESS via an internet
      support group, and our aim was to analyze the personal and familial medical
      histories of this large patient group for possible familial cancers aggregations
      in ESS patients. METHODS: A questionnaire regarding the personal and familial
      medical history was circulated among the members of the internet group, which was
      returned by 64 patients. RESULTS: At diagnosis of ESS the average age was 42
      years. Fifty percent had a history of long-term hormonal treatment. One patient
      each had a previous history of breast carcinoma, thyroid cancer and cutaneous
      malignant melanoma. One familial case of ESS was observed. At least one
      malignancy in the family was reported by 47% of patients, and the mother or
      father were affected in 26%. Multiple familial cancers were observed in 25% of
      ESS patients. The most frequent familial cancer was breast cancer (25%) followed
      by endometrial (8%), lung (7%) and prostate carcinoma (5%). CONCLUSIONS: Patients
      are young, report hormonal treatments and have a familial history of hormone
      dependent carcinomas. This suggests a strong genetic predisposition in the
      oncogenesis of ESS. Patients with ESS may suffer from an inherited genetic
      predisposition similar to familial breast and prostate carcinoma which may render
      them susceptible to hormone-dependent growth promotion and/or to cellular damage
      from particular estrogen metabolites of endometrial cells resulting in a ESS.

PMID- 15991529
TI  - The significance of Doppler flow in early detection of uterine sarcoma in older
      primigravida pregnancies.
AB  - During a four-year period we analyzed the significance, sensitivity and
      sensibility of myoma Doppler flow during pregnancy in relation to the course and
      outcome of the pregnancy and to later histopathological findings. By following 36
      older primigravidas with determined myomas, we observed the course of the
      pregnancies in all trimesters and analyzed myoma Doppler flow. In conditions
      where the resistance index showed the possibility of uterine sarcoma, the
      pregnancy was ended by surgery; not only was myomectomy performed but also
      complete uterine hysterectomy with the previous consent of the patient. Doppler
      flow was accepted as the authoritative parameter for non-invasive detection of a
      malignant process. Considering the obstetrical findings, other patients were
      delivered vaginally or operatively, but after puerperium they were subjected to
      control examinations and myomectomy because Doppler flow findings did not show
      any indications of sarcoma. By histopathological analysis, we received benign
      results in 31 cases, while in four cases where we decided on hysterectomy and
      surgical delivery, we received malignant results, i.e. leiomyosarcoma. In four
      cases of performed hysterectomy immediately after cesarean section, the
      resistance index (RI) of revascularization within the myoma was in the range
      between RI 0.30 +/- 0.02. Flows within the uterine artery were 0.54 +/- 0.03.

PMID- 15991530
TI  - Dynamics of cervical langerhans cell counts in the course of HPV-positive CIN
      treatment with the use of human recombinant interferon gamma.
AB  - OBJECTIVES: Langerhans cells play a pivotal role as professional antigens
      presenting cells in cervical epithelium, thus changes in their density or/and
      function may profoundly influence the proper activation of the afferent arm of
      immune response in cases of HPV-related intraepithelial lesions. AIM OF THE
      STUDY: Assessment of intraepithelial Langerhans cell count changes in CIN I/CIN
      II after human recombinant interferon gamma (IFNgamma) application and
      correlation with clinical outcome. MATERIAL & METHODS: The present study is a
      part of prospective trial on IFNgamma application in the treatment of CIN I/CINII
      associated with high-risk HPV infection. Seventeen subjects underwent uniform
      IFNgamma treatment (four intracervical injections in a two-day interval for a
      total dose of 6,000,000 IU). Langerhans cells were stained within cervical punch
      biopsy specimens with the use of polyclonal anti-S-100 antibody according to the
      three-step indirect peroxidase protocol, and their mean count calculated for the
      following groups: before IFNgamma treatment launching, immediately after
      completion of the treatment, and after two months of follow-up. RESULTS: The
      analysis revealed a rapid and significant increase in Lagerhans' cell count
      immediately after treatment completion (21.17/mm2 and 25.94/mm2, respectively, at
      p = 0.019) which further increased in the group of complete response (in 9
      subjects; 32.22/mm2). After transient elevation of the Langerhans' cell count it
      returned to a level even lower than initially in the non-responder group (4
      subjects; 20.25/mm2). CONCLUSION: Our data strongly support the observation from
      static studies suggesting that regression of HPV-related cervical lesions is
      associated with increased density of epithelial Langerhans cells.

PMID- 15991531
TI  - A pilot study of weekly docetaxel therapy for recurrent ovarian cancer, tubal
      cancer, and primary peritoneal cancer.
AB  - We investigated the efficacy and toxicity of salvage chemotherapy with weekly
      docetaxel for recurrent ovarian cancer, tubal cancer, and primary peritoneal
      cancer after treatment with regimens containing platinum or paclitaxel. The 15
      subjects were managed as outpatients and received at least two courses of
      docetaxel therapy (35 mg/m2 on days 1, 8 and 15). Antitumour activity was
      assessed radiologically and from the CA-125 level. Among five patients with
      measurable lesions, one showed partial remission and three showed stable disease.
      Based on CA-125 levels, there were three partial remissions and five patients
      with stable disease (progression-free survival was 7.5 months and 7.6 months,
      respectively). During 61 courses, the severe toxicities were grade 3
      leukopaenia/neutropaenia (6.7%) or grade 2 oedema and pleural effusion (13.3%).
      Weekly docetaxel may be useful salvage chemotherapy for recurrent ovarian cancer,
      tubal cancer, and peritoneal cancer, especially as tumour dormancy therapy.

PMID- 15991532
TI  - Colposcopy vs Hybrid Capture II assay in detection of cervical human papilloma
      virus infection.
AB  - PURPOSE OF INVESTIGATION: Considering the relationship between high-risk human
      papillomavirus types and the presence or subsequent development of cervical high
      grade preinvasive lesions, the aim of the study was to determine if the Hybrid
      Capture II test can be used to triage women with atypical colposcopic findings.
      METHODS: The study was carried out on 100 patients with suspicious colposcopy
      findings (suggestive of human papillomavirus infection) who underwent a cervical
      smear for human papillomavirus testing DNA Hybrid Capture II and direct biopsies
      for histopathological analysis. RESULTS: Sixteen patients were negative for human
      papillomavirus. Of the eight patients positive for high-risk HPV type, seven
      presented an abnormal transformation zone grade 2 (high-grade squamous
      intraepithelial lesion of the cervix at histopathology). There was a significant
      positivity of medium-high risk virus types in the cases with more abnormal
      colposcopy (chi2 = 7.44; p < 0.005). Histopathological findings of high-grade
      squamous intraepithelial lesions were registered in the patients positive for
      medium-high risk human papillomavirus types (chi2 = 7.66; p < 0.025).
      CONCLUSIONS: Based on these results it can be concluded that if a diagnosis of a
      high-grade squamous intraepithelial lesion has been made on the basis of
      colposcopic and histopathological findings, there is a high probability that the
      infection was due to one or more types of human papillomavirus. There are
      necessary further studies to interpretate both the advantages and disadvantages
      of intermediate triage procedures, like Hybrid Capture II testing, compared with
      immediate colposcopy.

PMID- 15991533
TI  - Gestational trophoblastic disease in Sanliurfa, southeast Anatolia, Turkey.
AB  - PURPOSE OF INVESTIGATION: This study was carried out to determine if the
      extremely high rate of gestational trophoblastic disease (GTD) previously
      reported from a center in Southeast Anatolia also applied in our area. METHODS:
      Records of GTD and deliveries in all hospitals in Sanliurfa during the period
      July 1998 to October 2003 were retrospectively studied. RESULTS: During the
      period, there were 6016 deliveries and 73 cases of GTD identified, giving an
      incidence of GTD of 12.1 per 1000 deliveries. Of these cases, 66 (90.4%) were
      diagnosed as having hydatidiform mole (64 complete and 2 partial), two (2.7%)
      invasive mole and five (6.9%) choriocarcinoma. Vaginal bleeding was the most
      common symptom. No clear correlations were found with gravidity or age.
      CONCLUSION: We confirmed that the incidence of GTD in Southeastern Anatolia is
      much higher than the national average and one of the highest in the world. Thus
      we explored possible reasons for this and suggest areas for further study.

PMID- 15991534
TI  - The significance of Doppler flow and anamnesis in the diagnosis of fallopian tube
      cancer.
AB  - By following Doppler flow of the small pelvis with laboratory parameters and
      anamnesis data, we obtained more precise diagnostic possibilities for timely
      discovering of malignant processes in adnexal region and fallopian tube. By
      following patients who had come for routine check ups, prompted by a positive
      family history for malignant processes, resistant indexes of blood vessels in the
      adnexal region and vascularisation pattern were determined. Out of 78 women
      observed in the postmenopausal period with diagnosed adnexal masses, we found two
      cases of fallopian tube cancer. Resistance indexes ranged between 0.20 and 0.30
      during a one-month period. Hystopathological analysis pointed to fallopian tube
      cancer. Besides Doppler flow, only patient history of amber extract use was
      significant. By CA 125 marker analysis, we found an increased value but not
      signifiant enough. Both patients had a positive family history according to the
      female hereditary line.

PMID- 15991535
TI  - Open surgical biopsy for nonpalpable breast lesions detected on screening
      mammography.
AB  - The aim of this retrospective clinical study was the analysis of histologic
      findings of nonpalpable breast lesions managed by open surgical biopsy. A series
      of 630 women underwent 664 preoperative localizations of nonpalpable,
      mammographically detected breast lesions during the last 10-year period.
      Indications for biopsy were (1) clustered microcalcifications, (2) solid mass,
      and (3) radiologic parenchymal distortion. The lesions were localized
      preoperatively using hook-wire methods, and all biopsies were performed under
      general anesthesia. Histopathology revealed carcinoma in 172 (25.9%) cases;
      noninvasive in 114 (66.3%) cases and infiltrating in 58 (33.7%) cases. The
      highest malignancy rate was found in cases with microcalcifications (112
      carcinomas out of 323 cases, 34.7%). Lymph node invasion was present in 25% of
      patients with invasive cancers. The hook-wire localization of nonpalpable breast
      lesions is a simple, accurate and safe method for detection of early breast
      cancers. Frozen section is feasible and accurate in the majority of these
      lesions, and therefore, diagnostic and therapeutic one-step surgical procedures
      could be performed.

PMID- 15991536
TI  - Diagnostic value of the photodynamic method in the evaluation of lesions of the
      uterine cervix.
AB  - The purpose of this study was to assess the efficacy of the photodynamic
      diagnosis (PDD) method in the diagnosis of lesions of the uterine cervix, as well
      as to establish its place and efficacy among currently available diagnostic
      techniques. In the case of lesions located on the cervix, the projected aim of
      the study was intended to be realised by performing a detailed comparative
      analysis of the examination results of the following: PDD, cytology, colposcopy
      and testing for the presence of viruses, as compared with histological evaluation
      of performed biopsies.

PMID- 15991537
TI  - Extragenital cystic lesions of peritoneum, mesentery and retroperitoneum of the
      female. Clinicopathological characteristics of 19 cases.
AB  - The clinicopathological characteristics are presented of 19 extragenital cystic
      lesions of female patients located at the retroperitoneum (9 cases), the
      mesentery (6 cases) and the peritoneum (4 cases). Median age was 42.3 years and
      the main symptom was abdominal pain. The cysts measured 4-27 cm in diameter and
      were classified as: epithelial (7/19), mesothelial (5/19), vascular (2/19),
      parasitic (1/19) and developmental in origin (4/19). Of the cases 18/19 were
      benign lesions and one case was a borderline mucinous cystic tumor.
      Immunohistochemistry by a streptavidin-biotin method was performed to investigate
      CEA transcripts (MoAb, Novosan), CA125 (MoAb, CIS Diagnostics), vimentin (MoAb
      Ve6, Novocastra), secretory component (a polyclonal antibody, DAKO), Factor VIII
      (MoAb, DAKO), CD34 (MoAb, Scytec), calretinin (a polyclonal antibody, Zymed, San
      Francisco, CA). Cytokeratins were of low and high molecular weight (Immunon, AE1
      MoAb). The results are helpful in the correct classification of various tumors.
      The treatment of choice is complete surgical resection of the tumors.

PMID- 15991538
TI  - Tumors of low malignant potential arising in the fallopian tube: case reports.
AB  - BACKGROUND: There is a paucity of information regarding fallopian tube tumors of
      low malignant potential (LMP) in the literature. CASE: We present two cases
      representing alternative management options of low LMP of the fallopian tube.
      CONCLUSION: Although low malignant potential tumors of the ovary are relatively
      common, there are few reported cases of tumors of LMP originating in the
      fallopian tube. Treatment has been extrapolated from tumors of LMP of the ovary,
      and conservative fertility-sparing surgery and complete staging procedure remains
      controversial. We urge continued reporting of these fallopian tube tumors of LMP
      to enhance understanding of these rare tumors and to develop a more cohesive
      treatment plan.

PMID- 15991539
TI  - Bilateral gonadoblastoma with extended calcification: case report of a tumor
      developing on dysgenetic gonads.
AB  - Gonadoblastoma is a rare tumor occurring almost exclusively in phenotypic females
      with intersex disorders and dysgenetic gonads. We report a case of gonadoblastoma
      in an 18-year old female who was admitted to our hospital for the investigation
      of primary amenorrhea. The patient underwent bilateral gonadectomy. A
      histopathologic study revealed streak gonads with extended calcification and
      bilateral gonadoblastoma. We describe the histopathologic features of
      gonadoblastoma and the pattern of its potential malignant transformation.
      Difficulties in the histological diagnosis of this rare tumor are also discussed.
      The need for early prophylactic removal of dysgenetic gonads, especially in
      patients that carry the Y chromosome, is emphasized.

PMID- 15991540
TI  - Primary leiomyosarcoma of the fallopian tube: a case report.
AB  - A primary leiomyosarcoma (LMS) arising from the left fallopian tube in a
      perimenopausal 48-year-old woman is reported. Primary tubal LMS is an uncommon,
      exceedingly rare neoplasm, accounting for only a few reported cases so far. To
      our knowledge, the present case is the 17th tubal LMS reported in the English
      language literature. The diagnosis is usually made at the time of laparotomy for
      a pelvic or adnexal mass or other gynaecological indications. As in ovarian
      neoplasms, the mainstay of treatment is represented by debulking surgery
      consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy,
      random biopsies, peritoneal washing and excision of all the abdominal tumour
      masses. Although the approach is radical, the clinical behaviour is very poor.
      The role of adjuvant radio- or chemotherapy still remains unsolved.

PMID- 15991541
TI  - Bilateral metastatic breast cancer as the first manifestation of ovarian cancer:
      case report.
AB  - BACKGROUND: Breast metastasis from primary ovarian cancer is extremely rare. The
      rarity of this finding may be the reason for its common misinterpretation as
      primary breast carcinoma. DESIGN: Case report. SETTING: A university hospital.
      RESULTS: A case of a patient with primary ovarian papillary serous
      cystadenocarcinoma who initially presented with a solitary bilateral breast mass
      and abdominal distention is reported. CONCLUSIONS: Blood-borne metastasis from
      the ovary to the breast can show a varied clinical picture that should be
      differentiated from that of primary breast carcinoma.

PMID- 15991542
TI  - Palmar fasciitis and polyarthritis associated with secondary ovarian carcinoma.
      Case report.
AB  - Palmar fasciitis and a polyarthritis syndrome (PFPAS) is an uncommon
      paraneoplastic syndrome often associated with occult neoplasms, including ovarian
      and pancreatic carcinomas. A 67-year-old patient with presenting symptoms of
      PFPAS is reported. Twelve months after onset of the symptoms an ovarian and
      pancreatic adenocarcinoma was diagnosed synchronously. The spread pattern and
      other features of the neoplasm indicate that it was a primary pancreatic cancer
      with ovarian metastasis. Surgical excision of tumor and adjuvant chemotherapy
      caused remission of symptoms. A literature review of PFPAS and secondary ovarian
      neoplasms with a pancreatic primary tumor is discussed.

PMID- 15991543
TI  - Mixed serous and endometrioid carcinoma of the fallopian tube: a case report with
      literature review.
AB  - Malignant neoplasms of the fallopian tube are the rarest of the gynecologic
      cancers. The frequency of histologic subtypes has been difficult to ascertain
      from the literature because most authors have not classified these tumors
      according to their cell types. Papillary serous adenocarcinoma appears to be the
      most common histologic type. On the contrary, mixed cell types of fallopian tube
      carcinoma have rarely been reported in the literature. A case of mixed serous and
      endometrioid carcinoma of the fallopian tube is presented and the related
      literature is reviewed.

PMID- 15991544
TI  - Image findings of a tailgut cyst. Case report and short review of the literature.
AB  - We present a case of retrorectal hamartoma (tailgut cyst). Imaging findings on
      ultrasound, computed tomography and magnetic resonance imaging, pathologic
      findings, as well as the diagnostic pitfalls during the patient's management are
      documented. As it is a rare lesion with a non specific clinical presentation, it
      is usually misdiagnosed. Our aim is to present image characteristics of these
      lesions in all modalities and include retrorectal hamartomas in our differential
      diagnosis in patients with lesions with similar image findings.

PMID- 15991545
TI  - [Long-term results of uncemented hip arthroplasty for dysplastic coxarthrosis].
AB  - The purpose of the study was to evaluate the long-term results of uncemented
      total hip arthroplasty (THA) in young patients (below 50 years of age) with
      dysplastic coxarthrosis. In the last 20 years, 862 primary uncemented THA, were
      implanted in our Institution. This surgery was performed in 459 patients. From
      this group 220 hips in 177 patients (167 women and 10 men), who had dysplastic
      coxarthrosis, were included in our study. The left hip was operated in 66 and the
      right one in 68 patients. Bilateral surgery was performed in 43 cases. The means
      age at the time of hip surgery was 38.3 years (range from 18 to 49 years). The
      mean follow-up was 9.3 years (range from 2 years to 18.6 years). In 167 (75.8%)
      patients the operative treatment of DDH was performed during the early childhood
      (Colonna-Zahradnicek procedures, Dega, Pemberton and Salter pelvic osteotomies).
      Only 39 (17.7%) patients were treated in the childhood conservatively by means of
      overhead extension, Frejka pillow or Pavlik harness. All patients were evaluated
      clinically and radiological. For clinical evaluation the classification system
      proposed by Merle d'Aubigne and Postel with Chamley modification was used. For
      radiological evaluation of the steam implantation the classification system
      proposed by De Lee and Chamley was used and for the cup implantation the system
      by Gruen and Moreland. The femoral head displacement prior to THA surgery was
      classified according to Crowe at all. classification. Based on above mentioned
      criteria in 26 hips (11.8%) the final result was graded as very good, in 61 cases
      (27.7%) as good, in 94 hips (42.7%) as satisfactory and in the remaining 39 cases
      (17.8%) the final result was poor. We observed a very strong correlation between
      clinical and radiological results. According to Crowe and all. classification, in
      class I we noted 19 (61.3%) very good, 11 (35.5%) good, 1 (3.2%) satisfactory
      results. In class II in 5 cases (6.6%) the results was very good, 25 (32.9%) good
      and in 39 (51.3%) satisfactory results. In class III only in 2 cases the final
      result was graded as very good, and good in 23 hips (25.8%). In class IV there
      was no very good result, and we observed 19 (21.4%) poor results. In analyzed
      group in 37 (16.8%) patients the revision hip surgery was necessary because of
      aseptic prosthesis loosening. CONCLUSIONS: The treatment of dysplastic
      coxarthrosis by means of THA is difficult. The high level of experience is
      necessary to perform this type of surgery. This type of THA should be performed
      only in selected orthopaedic centers. Starting the surgery one has to think about
      complications.

PMID- 15991546
TI  - [Effect of gastroesophageal reflux in children on x-ray imaging of the lungs].
AB  - The usefulness of radiologic examination in the diagnosis of aspiration pneumonia
      in infants. The aim of the study was to estimate whether the connection between
      the localisation and radiological findings on the plain X-ray chest examination
      exists in the group of 121 infants and young children, age 1 to 24 month (77 boys
      and 44 girls), treated for pneumonia and gastroesophageal reflux disease (GERD),
      established by 24-hour esophageal pH-monitoring. In all children the diagnosis of
      pneumonia were made on admission to hospital by physical and X-ray chest
      examinations. GERD, in accordance with consensus ESPAGAN, was diagnosed in the
      group of 65 children. Children with abnormal results of pH-monitoring had
      significantly more changes in the lower parts of the right lung and in the
      intermediate and the lower parts of the left lung. There were no difference in
      radiological appearance between the changes suspected to the aspiration etiology
      and other pneumonic changes in the group of 56 children with normal pH
      investigation. Additionally, there was no significant difference in the frequency
      of atelectasis, emphysema and/or enlargement of the thymus between both groups.

PMID- 15991547
TI  - [A blinded comparison of palatability of 13 common pediatric antibiotic
      suspensions].
AB  - Non-compliance is one of the leading reasons of therapy failure in case of
      antibiotherapy of respiratory tract infections in children. The organoleptic
      characteristic of the antibiotic suspension has strong influence on compliance in
      children. The aim of the present study was to compare taste and the other
      organoleptic factors of commonly prescribed antibiotics in order to find which of
      them are palatable to the extent which may positively influence patient
      compliance. METHODS: 13 antibiotic suspensions were arbitrary chosen for the
      comparison. These drugs were blindly evaluated by 25 volunteers as to the
      appearance, smell, texture, taste and aftertaste compared to amoxycillin
      (Amotaks) as a reference dug. The overall score was calculated, as well. In the
      statistical analysis Duncan's test was used. RESULTS: The important diversity of
      scores of assessed antibiotics was observed in every category. In most cases
      clindamycin and macrolides obtained the lowest scores, penicillins and co
      trimoxazol--medium ones and cephalosporins--the best scores. Among penicillins,
      amoxicillins with clavulanic acids were scored lower than pure amoxicillins. In
      overall score, different preparations of the same substance obtained similar
      scores, statistically non-different, with one exception for clarithromycin, in
      which Klacid was characterized by better palatability. CONCLUSION: Observed
      differences in organoleptic characteristics of studied drugs may significantly
      influence patient compliance and therefore should be taken into consideration in
      the case of antibiotic selection for the treatment of infection in children.

PMID- 15991548
TI  - [Teleneurology: a new form of physician--patient communication].
AB  - The Internet is an increasingly popular medical information source. 281
      electronic mails to a neurologist concerning medical consultation were analyzed.
      Demographic features of senders and subject of electronic mails were
      characterized.

PMID- 15991549
TI  - [Ultrasonographic evaluation of kidneys in type-2 diabetes patients without overt
      nephropathy and with chronic renal failure].
AB  - Ultrasonographic evaluation of the kidney size is a useful method for assessment
      of the progression and in some cases the type of nephropathy. Diabetic
      nephropathy in type 2 diabetes is not only the cause of chronic renal failure
      (CRF), but also non-diabetic renal diseases. Besides giving the clinical picture,
      USG evaluation can be useful for qualification of the main cause of CRF in type 2
      diabetes patients (pts). In the study we attempted to evaluate if type 2 diabetic
      pts without nephropathy have significant changes in the USG kidney picture
      compared with type 2 diabetic pts with CRF. The study was conducted on two groups
      of type 2 diabetic pts. Group I consisted of 44 pts (18 men, 26 women) without
      overt nephropathy with mean creatinine clearance (CrC) calculated by Cockcroft
      Gault formula 78.7 +/- 3 ml/min. Group II consisted of 48 pts (23 men, 25 women)
      with CRF: 30 pts with mean CrC 25.8 +/- 2 ml/min and 18 CAPD (continuous
      ambulatory peritoneal dialysis) pts. The mean age was similar in both groups
      (62.5 vs 64.5). Small kidney was defined when USG kidney length was less than 9
      cm. In Group I 33 pts (75%) had normal size kidneys, 11 pts (25%) had small
      kidneys with postinflammatory changes, and 3 pts had single cysts. In Group II 9
      pts (18.8%) had normal size kidneys. We found small kidneys in 39 pts (81.2%) and
      single cyst in 7 pts (15%). None of the patients had acquired cystic kidney
      disease. In our study we found that most of type 2 diabetic pts with CRF had
      small kidneys which means that they had ischemic, hypertonic or inflammatory
      nephropathy accompanying type 2 diabetes.

PMID- 15991550
TI  - [Biochemical markers of bone formation activity in children with neoplasms].
AB  - The aim of the study was the analysis of biochemical markers of bone turnover in
      children with neoplasms comparing with the group of healthy children. We explored
      the relationships between sex, pubertal development and type of neoplastic
      disease. 85 children (53 boys) with newly diagnosed neoplasms: 48 with acute
      lymphoblastic leukaemia (ALL), 13 with Hodgkin's disease and 22 with solid tumors
      (group I) and 111 healthy children (group II) were studied. We measured in
      plasma: 1. bone specific alkaline phosphatase (BALP), 2. osteocalcin (OST) as the
      markers of bone formation and 3. ICTP (cross-linked telopeptide of type 1
      collagen), 4. parathormon (PTH), as the markers of bone resorption. RESULTS: 1.
      In the group of boys with neoplasms osteocalcin and BALP values were lower than
      in healthy boys: OST 51.2 ng/ml +/- 35.3 vs 85.8 ng/ml +/- 35.96, p < 0.0001,
      BALP 105.6 U/L +/- 56.8, p < 0.0001. The girls had lowered values of osteocalcin
      (45.55 ng/ml +/- 40.9 vs 71.94 ng/ml +/- 28.75, p < 0.0008) and ICTP (11.25 U/L
      +/- 3.38 vs 15,47 U/L +/- 5.33, p < 0.0016). The differences were also observed
      in comparison with the pubertal stage except for the boys in V0Tanner stage. 2.
      The values of OST and BALP were lower in children with ALL than in the children
      with solid tumours (p < 0.01). The values of ICTP did not depend on the type of
      disease, sex and pubertal stage, except the children before puberty. 3. In all
      group we found the correlation between OST and ICTP (r = 0.45, p < 0.05), BALP
      and ICTP (r = 0.45, p < 0.05). This correlation was observed in children with
      leukaemia (r = 0.55, p < 0.05), especially in girls (r = 0.9, p < 0.05).
      CONCLUSIONS: The markers of bone turnover are decreased in children with newly
      diagnosed neoplasms, especially with ALL.

PMID- 15991551
TI  - [Colorectal cancer patients treated in surgical departments of the Lublin region-
      clinical and pathologic features obtained from the Lublin Colorectal Cancer
      Registry].
AB  - Introduction of regional screening programs should be based upon the coherency of
      epidemiological data and the selection of specific patient groups. This would
      have significantly reduced costs and improve medical benefits. The aim of the
      study was to determine the number of patients with colorectal cancer that
      underwent surgical treatment and achieving clinical and/or pathological data
      which would be the basis in planning regional screening programs. The data of
      1,770 patients that underwent surgical treatment during 1991-2001, in the
      province of Lublin was attained from the assessment of questionnaires. The
      results show an increase in morbidity of colorectal cancer in patients over 50
      years old in both sexes, irrespectively to primary tumor localization. In 78% of
      the patients tumors were localized in the distal region of the splenic flexure of
      colon. The frequency in occurrence of advanced colorectal cancer, morbidity and
      peri-operative mortality increased due to the patients older age. The results of
      this research suggest the need to proceed with screening programs in patients
      over 50 years old with the use of flexible sigmoidoscopy as a method which
      diagnoses approximately 80% of colorectal cancers.

PMID- 15991552
TI  - [Evaluation of thromboembolic complications in children treated for acute
      lymphoblastic leukemia with Vascuport catheters].
AB  - The aim of the work was to evaluate the safety of Vascuport catheter long-term
      application in children treated for acute lymphoblastic leukemia (ALL). 21
      children treated in the Department of Pediatric and Hematology in Zabrze were
      enrolled in the study. Echocardiography and ultrasonography were performed to
      examine Vascuport catheter in the central vein. Coagulation parameters were
      estimated too. None of the children presented symptoms of pulmonary embolism or
      venous thrombosis. Thrombotic material was found on the course of Vascuport
      catheter in 5 (23%) children. Changes in the hemostatic system: increased d
      dimmer levels in 2 (9%), increased fibrinogen level in 7 (33%), decreased value
      of APC-R in 7 (33%) and protein C in 8 (38%) children were observed. Changes of
      hemostatic system and presence of thrombotic material on the course of Vascuport
      catheter in 23% of the patients with ALL imply the necessity of rigorous
      monitoring of haemostatic system as well as Vascuport catheter in the central
      vein. In case the risk factors of thrombotic events or their clinical symptoms
      are present anticoagulant therapy should be introduced.

PMID- 15991553
TI  - [Efficacy of specific immunotherapy in the treatment of children and youngsters
      suffering from atopic dermatitis. Part I. Evaluation of clinical score].
AB  - Despite undoubted progress in the field of allergology and clinical immunology we
      still lack an effective and secure therapeutic methods in many cases of atopic
      dermatitis. The aim of the study was to evaluate efficacy of specific
      immunotherapy performed for the time period of 3 years with Novo-Helisen Depot
      allergy vaccines in the group of 36 children and youngsters with atopic
      dermatitis, allergic to house dust mites (24 patients) and grass pollen allergens
      (12 patients). The control group consisted of 20 patients with atopic dermatitis
      and analogous IgE-mediated airborne allergy treated with conventional methods.
      Clinical evaluation of patients was performed before treatment and after 36
      months of therapy and was based on severity and extensiveness of skin
      inflammation in atopic dermatitis index: W-AZS. Clinical efficacy of specific
      immunotherapy was significantly higher than efficacy of conventional methods (p <
      0.001). It was concluded that in selected patients with atopic dermatitis with
      IgE-mediated airborne allergy this method of treatment could be a promising
      alternative.

PMID- 15991555
TI  - [The treatment of clinically silent breast lesions].
AB  - Analysis of a diagnostic procedure leading to the clinical diagnosis and
      treatment of nonpalpable lesions in breast was presented in the paper. 668 women
      with breast lesions were treated in our department between 1995 and 2001.
      Nonpalpable lesions were detected in 68 women. The following diagnostic-treatment
      algorithm was used: case history and physical examination, radiological
      examination, hooked wire localisation under mammography or USG, breast surgical
      biopsy, intra-operative histological examination, further procedures according to
      morphological changes found in patients. Mammography was performed in 68
      patients. Stereotactic needle biopsy under mammography was done in 61 patients
      (DXRBL-18-9 needle was used). The lesions were localized under USG in 7 patients.
      Surgical biopsy and X-Ray examination of the removed specimen was performed in 68
      patients. Intra-operative histological examination revealed benign lesions in 54
      women whereas malignant lesions were found in 14 women. Post-operative
      complications were present in 8 patients. Nonpalpable breast lesions require
      individual, planned diagnostic treatment. Stereotactic needle biopsy not only
      allows definitive surgical removal of malignant lesions within margins of normal
      breast tissue but also gives a good cosmetic effect. Complex diagnostics together
      with standardized procedure ensure the highest rate of correct diagnosis and
      lower the risk of diagnostic failures.

PMID- 15991554
TI  - [Hematologic parameters in Polish centenarians].
AB  - We undertook this study to characterize the haematological indices in centenarian
      subjects who should be an excellent group to study the mechanisms of
      physiological aging. This study is a part of the Polish Centenarians Program co
      ordinated by the International Institute of Molecular and Cell Biology in Warsaw.
      We examined 89 subjects aged 100 to 111 (14 males and 75 females). Mean values of
      all haematological parameters were within the normal range in females. In males,
      haemoglobin level (Hb), red blood cell count (RBC) and hematocrit (Hct) were
      slightly lower than WHO references (12.7 +/- 1.3 g/dl, 4.10 +/- 0.48 M/ml and
      38.4 +/- 3.8%, respectively). However, anaemia was more frequent in females than
      in males (57.1% vs 29.1%, p < 0.05). In females with anaemia there was a tendency
      to decrease its severity with age. In the oldest group (aged 105-111 years) Hb
      and Hct had a tendency for lower values vs the youngest group (100-101 years)
      (10.1 +/- 1.8 g/dl vs 11.6 +/- 0.1 g/dl, p = 0.067 and 30.9 +/- 5.0% vs 35.0 +/-
      0.3%, p = 0.067). Additionally, in the youngest group there were three females
      with severe anaemia (Hb < 9.0 g/dl) whereas in the oldest group all females with
      anaemia had Hb above 11.0 g/dl. In males the analysis was not undertaken because
      of small group of studied subjects. In conclusion, anaemia seems to be a
      relatively common problem in studied centenarians. Severe anaemia seems to be an
      eliminating factor in centenarian women.

PMID- 15991556
TI  - [Health-related quality of life as a new clinical problem].
AB  - The authors gives a basic definition and describe methods of health-related
      quality of life (HRQL) analysis emphasising at same time the role of HRQL
      quantification in contemporary clinical practice. The historical evolution of the
      term HRQL was given and the future perspectives of research in this field were
      underlined.

PMID- 15991557
TI  - [In vitro cell culture technology in cosmetology research].
AB  - For ages the humanity has been looking for all kind of active substances, which
      could be used in improving the health and the appearance of our skin. People try
      to find out how to protect the skin from harmful, environmental factors. Every
      year a lot of new natural and synthetic, chemical substances are discovered. All
      of them potentially could be used as a cosmetic ingredient. In cosmetology
      research most of new xenobiotics were tested in vivo on animals. Alternative
      methods to in vivo tests are in vitro tests with skin cell culture system. The
      aim of this work was to describe two-dimensional and tree-dimensional skin cell
      cultures. Additionally, in this work we wanted to prove the usefulness of in
      vitro skin cell cultures in cosmetology research.

PMID- 15991558
TI  - [Cardiovascular abnormalities in patients with obstructive sleep apnoea
      syndrome].
AB  - The activation of adrenergic and renin-angiotensin-aldosterone (RAA) systems
      observed in patients with obstructive sleep apnoea syndrome (OSA) strongly
      affects functional status of the cardiovascular system. In this paper we discuss
      the link between obstructive sleep apnoea syndrome and common cardiovascular
      diseases such as systemic and pulmonary hypertension, ischaemic heart disease,
      stroke, arrhythmia and ventricular hypertrophy. We also present the importance of
      early pharmacologic treatment in preventing cardiac hypertrophy and ventricular
      dysfunction in patients with obstructive sleep apnoea syndrome.

PMID- 15991559
TI  - [Abdominal compartment syndrome as advanced abdominal hypertension].
AB  - The aim of the article is to present the definition and criteria of diagnosis of
      abdominal compartment syndrome (ACS) due to abdominal hypertension. Epidemiology
      of ACS is discussed. Secondary ACS is described. There is also an overview of
      clinical consequences and a scheme for ACS management.

PMID- 15991560
TI  - [Prophylaxis, diagnosis and conservative treatment of chronic lower extremities
      ischaemia].
AB  - The most frequent cause underlying the chronic lower extremities ischaemia is
      atheromatosis. As the basic symptom of the disease, intermittent claudication
      exerts essential impact upon the state of patient's health as it causes the
      limitation or the loss of the ability of unassisted walking and, effectively,
      also the deterioration of the quality of his or her life. The discovery of the
      etiopathogenesis of atheromatosis and correct assessment of risk factors involved
      are the elementary conditions of proper administering of pharmacological
      treatment as well as the basis for adequate planning of necessary prophylactic
      steps. In such cases, the diagnostic process ought to involve obtaining data from
      the patient's medical history and his or her physical examination, as well as
      determining his or her ankle-brachial index (ABI) and information derived from
      ultrasonographic examination performed at non-invasive diagnostics laboratory.
      The resultant treatment ought to focus on the improvement of the patient's
      functional efficiency. Before the necessity of surgical treatment is considered
      it is recommended to determine a plan for conservative treatment. Adequate
      diagnosis combined with an early commencement of conservative treatment in the
      cases of chronic lower extremities ischaemia frequently prove effective in
      arresting the development of the disease and, consequently, render invasive
      treatment unnecessary--thus resulting in the improvement of patient's quality of
      life.

PMID- 15991561
TI  - [Cavernous hemangiomas of the adrenal glands--rare incidentaloma type tumors].
AB  - Cavernous hemangiomas of the adrenal glands are extremely rare benign lesions and
      most are incidental findings. The increasing frequency of the adrenal masses
      detection is due to the widespread use of the contemporary imaging techniques. We
      review incidence, pathology, clinical features, diagnostic and therapeutic
      treatment of the adrenal cavernous hemangiomas.

PMID- 15991562
TI  - [Radiologic and clinical aspects of developmental anomalies of the chest wall].
AB  - The radiological and clinical presentations of developmental anomalies of
      anterior chest wall are reported. The authors describe the main diagnostic and
      therapeutic issues including corrective surgery, its complications and progress
      in diagnostic imagining. The methods and parameters used in the assessment of the
      degree of chest wall deformity in patients with pectus excavatum (PE) and pectus
      carinatum (PC) are also discussed.

PMID- 15991563
TI  - [Arthroscopy of the knee joint--history and present state].
AB  - This study presents, based on the literature, data and own experience, the
      history, the development and current trends of the knee joint arthroscopy.

PMID- 15991564
TI  - [Antiphospholipid syndrome].
AB  - The antiphospholipid syndrome is considered to be one of the most common
      autoimmunological diseases. This paper is a review of contemporary literature
      data concerning pathogenesis and clinical and laboratory diagnostic criteria.
      Wide clinical symptomatology of the syndrome, differential diagnosis as well as
      diagnostic, therapeutic and preventive regimens are presented.

PMID- 15991565
TI  - [Metabolic or immunometabolic syndrome?].
AB  - Understanding the risk and pathogenesis of the numerous disorders including the
      insulin resistance/metabolic syndrome has changed meaningfully in the recent
      years. The remarkable similarity of the risk factors of cardiovascular disease,
      type 2 diabetes mellitus, obesity and atherogenic dyslipidemia induced to search
      for their pathophysiology. The aim of these examinations was to determine if the
      inflammatory state is a soil of the metabolic syndrome as in atherosclerosis?
      Increasing number of studies demonstrates a series of statistically significant
      correlations between the inflammatory markers and diseases present in the
      metabolic syndrome. It allows for the reasonable basis of hypothesis that
      chronic, mild inflammatory state underlies not only the cardiovascular disease,
      but also is the soil of the metabolic syndrome pathologies and its complications
      development. Both associations between the inflammatory mediators as CRP,
      fibrinogen, alpha1-glycoproteins, leptin, TNFalpha, PAI-1 and the metabolic
      syndrome variables, chiefly obesity, seem to suggest that both atherosclerosis
      and insulin resistance are the results of chronic activation of the nonspecific
      (innate) immune system. According to this hypothesis, daily stresses as traumas,
      infections and emotions would lead to primary immune and neuroendocrine systems
      alterations. By this manner, whole body metabolic disorders and metabolic
      syndrome component progressive reveal would approach. In this context, metabolic
      syndrome might be defined as an immunemetabolic disease.

PMID- 15991566
TI  - [Fournier's gangrene--serious complication of perianal abscess].
AB  - Authors present the case of Fournier's gangrene in course of perianal abscess.
      They pay attention to fulminant clinical course of superficial perineal fascia
      necrosis caused by mixed bacterial flora included aerobes and anaerobes and
      difficulties of treatment. They indicate the possibility of septic shock and
      multiple organ failure leading to death, in spite of intensive surgical and
      pharmacological treatment.

PMID- 15991567
TI  - [Ciprofloxacin-induced acute non-oliguric renal failure in patient with chronic
      glomerulonephritis].
AB  - We report a case of ciprofloxacin-induced acute non-oliguric renal failure that
      developed in a patient with chronic glomerulonephritis. Withdrawal of the drug
      led to normalization of renal function within 31 days without further specific
      therapy. Thus, clinicians should be aware of this rare but severe entity.

PMID- 15991568
TI  - [Diagnostic difficulties in rare causes of gastrointestinal bleeding].
AB  - Peptic and duodenal ulcer and haemorrhagic gastritis are the most common causes
      of gastrointestinal bleeding. Pathologic changes of the small intestine are rare
      and difficult to diagnose. The aim of the study is to evaluate the diagnostic
      strategy regarding patients with gastrointestinal bleeding of obscure origin.
      From 1996 to 1999, 626 patients were treated for gastrointestinal bleeding. There
      were difficulties in finding the source of bleeding in three out of 626 patients.
      Endoscopy of the upper and the lower gastrointestinal tract, hydrosonography of
      the large intestine and gastrointestinal passage were performed in these three
      patients. The site of bleeding was not determined after the above mentioned
      medical examinations. Three patients underwent exploratory laparotomy, and two of
      them also intraoperative endoscopy of the small intestine. One patient had tumor
      of the small intestine, and pathologic examination revealed leiomyoma. One
      patient had Meckel's diverticulum with presence of ectopic gastric mucosa
      diagnosed. One patient had inflammatory infiltration in the distal ileum. The
      presence of chronic, non-specific inflammation was proved by histologic
      examination. In case of patients for whom it was difficult to determine the
      source of gastrointestinal bleeding the very reason for such a bleeding is often
      found in the small intestine. It frequently happens that laparotomy and
      intraoperative endoscopy of the small intestine allows making the diagnosis.

PMID- 15991569
TI  - [Ambulatory haemorrhoidectomy using laser CO2].
AB  - There is presented our experience in surgical haemorrhoids treatment using CO2
      laser. There were 68 operations in 37 patients in outpatient clinic. There were
      two cases of anal fissure and no postoperative bleeding during postoperative
      period.

PMID- 15991570
TI  - Effect of caspase inhibitors on the post-thaw motility, and integrity of acrosome
      and plasma membrane of cryopreserved equine spermatozoa.
AB  - The present study was designed to test the hypothesis that addition of
      anticaspase cocktails (inhibiting caspases and thus blocking apoptosis) to the
      extenders increases the post-thaw viability of equine spermatozoa. The addition
      of caspase inhibitors failed to improve the acrosome and plasma membrane
      integrity of spermatozoa, suggesting that in equine sperm cryopreservation
      protocols, the addition of these caspase inhibitors to cryopreservation medium
      may not be beneficial in protecting the sperm from the stress of
      cryopreservation.

PMID- 15991571
TI  - A new method for isolation of leukocytes from the peripheral blood of amphibians
      [Bufo himalayanus, (Gunther)] and study of their surface morphology by scanning
      electron microscopy.
AB  - Using percoll as the density gradient, a new single step method to isolate
      leukocytes from the peripheral blood of amphibians (B. himalayanus) has been
      described. Isolated leukocytes were photographed under the scanning electron
      microscope and an attempt has been made to characterize the leukocyte population
      on the basis of surface morphology. Apart from regular blood cell types, B.
      himalayanus have slender, elongated and slightly curved leukocyte type cells in
      their peripheral blood. Such slender elongated cells were absent in the blood of
      a related species B. stomnaticus and hence could not be categorized under the
      known blood cell types.

PMID- 15991572
TI  - Lethal, oedema, haemorrhagic activity of spotted butterfish (Scatophagus argus,
      Linn) sting extract and its neutralization by antiserum and pharmacological
      antagonists.
AB  - An attempt has been made in this communication to develop antiserum in rabbit
      against Scatophagus. argus sting extract. Antiserum did not neutralized the sting
      extract induced proinflammatory and haemorrhagic activity but successfully
      neutralized lethality upto 2LD50. Cyproheptadine, indomethacin and BW 755C
      pretreatment significantly reduced sting extract induced proinflammatory
      activity. The haemorrhagic activity of sting extract was significantly inhibited
      by temperature, UV-exposure, EDTA, cyproheptadine, indomethacin and BW 755C
      pretreatment. The results conclude that the local effects of S.argus venom is
      likely to be mediated through release of mediators and may be encountered by
      pharmacological antagonists better than the antiserum.

PMID- 15991573
TI  - Possible analgesic and anti-inflammatory interactions of aspartame with opioids
      and NSAIDs.
AB  - The purpose of the present study was to investigate analgesic and anti
      inflammatory properties of aspartame, an artificial sweetner and its combination
      with various opioids and NSAIDs for a possible synergistic response. The oral
      administration of aspartame (2-16mg/kg, po) significantly increased the pain
      threshold against acetic acid-induced writhes in mice. Co-administration of
      aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po)
      significantly reduced acetic acid-induced writhes as compared to effects per se
      of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1
      mg/kg, po) was co-administered with aspartame it reduced the number of writhes as
      compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly
      decreased carrageenan-induced increase in paw volume and also reversed the
      hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The
      study indicated that aspartame exerted analgesic and anti-inflammatory effects on
      its own and have a synergistic analgesic response with conventional analgesics of
      opioid and non-opioid type, respectively.

PMID- 15991574
TI  - Effect of cholesterol and 7-beta hydroxycholesterol on glutathione status and
      nitric oxide production in murine peritoneal macrophages.
AB  - Present study was conducted to observe the effect of cholesterol and oxidized
      cholesterol (7beta-hydroxycholesterol,7beta-OH) on the nitric oxide (NO)
      production and the redox ratio by lipopolysaccharide-stimulated macrophages. Dose
      dependent decrease in NO levels was seen with both cholesterol and 7beta-OH at
      different incubation intervals (6,12,18,24 hr) and concentrations
      (2.5,5,7.5microg/ml). On comparison, a significant decrease in the NO was
      observed at 24 hr interval in 7beta-OH exposed cells with all respective
      concentrations of cholesterol. Incubation with 7beta-OH also resulted in
      significant increase in levels of oxidized glutathione (GSSG) and decrease in
      reduced glutathione (GSH), while cholesterol showed no effect on GSSG levels.
      Moreover, GSH levels were lowered only at highest concentration (7.5microg/ml),
      and at longer incubation intervals (18,24 hr) with cholesterol exposure. This
      altered the redox status in both cholesterol/7beta-OH treated macrophages.
      Increased redox ratio and decreased NO levels indicated increased oxidative
      stress and decreased vasodilation by 7beta-OH compared to cholesterol.

PMID- 15991575
TI  - Extract of gum resins of Boswellia serrata L. inhibits lipopolysaccharide induced
      nitric oxide production in rat macrophages along with hypolipidemic property.
AB  - Boswellia serrata, Linn F (Burseraceae) is commonly used in Indian system of
      medicine (Ayurvedic) as an anti-inflammatory, analgesic, anti-arthritic and anti
      proliferative agent. This study was planned to investigate the water-soluble
      fraction of the oleoresin gum of Boswellia serrata (BS extract) on
      lipopolysaccharide (LPS) induced nitric oxide (NO) production by macrophages
      under in vivo and in vitro conditions. In the previous condition, rats were fed
      on atherogenic diet (2.5% cholesterol, 1% cholic acid, 15.7 % saturated fat)
      along with the BS extract for 90 days. Blood was collected for lipid profile and
      toxicological safety parameters. Peritoneal macrophages were isolated and
      cultured to see the LPS induced NO production. Under in vivo experiment, BS
      extract significantly reduced serum total cholesterol (38-48 %), increased serum
      high-density lipoprotein- cholesterol (HDL-cholesterol, 22-30%). Under in vitro
      experiments with thioglycolate activated macrophages, it inhibited LPS induced
      (NO) production with IC 50 value at 662 ng /ml. Further, this fraction, in the
      dose of 15 mg/100 g body wt for 90 days, did not show any increase in serum
      glutamate-pyruvate transaminase (SGPT) and blood urea, in normal control animals.
      However, it significantly reversed the raised SGPT and blood urea in the
      atherogenic diet-fed animals. Transverse section of liver and kidney also
      supported its protective effect. Thus it may be concluded that water extract of
      Boswellia serrata possesses strong hypocholesterolemic property along with
      increase in serum HDL. It inhibits the LPS induced NO production by the activated
      rat peritoneal macrophages and show hepato-protective and reno-protective
      property.

PMID- 15991576
TI  - Desmodium gangeticum: a potent anti-ulcer agent.
AB  - The present study was designed to investigate anti-ulcerogenic property of
      ethanolic extract of Desmodium gangeticum (DG) against cold restraint (CRU, 2 hr
      cold restraint stress), aspirin (ASP, 150 mg/kg orally), alcohol (AL, absolute
      alcohol 1 ml/200gm) and pyloric ligation (PL, 4 hr pylorus ligation) induced
      gastric ulcer models in Sprague Dawley rats, and histamine (HST, 0.25 mg/kg)
      induced duodenal ulcer in guinea pigs. We found that DG at a dose of 200mg/kg,
      (orally), markedly decreased the incidence of ulcers in all the above models. DG
      showed significant protection against CRU (68.37%), AL (88.87%), ASP (38.2%), PL
      (40.63%) and HST (63.15%) induced ulcer models, whereas standard drug omeprazole
      (OMZ) showed protection index of 83.86, 56.35, 70.31 and 84.21%, respectively in
      CRU, ASP, PL and HST models. Sucralfate as standard drug showed 92.64% protection
      in AL model. DG significantly reduced acid secretion 41.61%, whereas OMZ produced
      43.13% reduction. Treatment with DG showed increase in mucin secretion by 56.17%,
      whereas OMZ showed 12.45% increase. Anti-ulcer effect of DG may be due to its
      cytoprotective effect along with antisecretory activity and could act as a potent
      therapeutic agent against peptic ulcer disease.

PMID- 15991577
TI  - Hypolipidemic effect of methanolic extract of Dolichos biflorus Linn. in high fat
      diet fed rats.
AB  - High fat diet fed rats showed significant increased levels of plasma and tissue
      total cholesterol, triglycerides, free fatty acids, phospholipids, plasma LDL
      cholesterol and decreased level of plasma HDL cholesterol. Methanolic extract of
      D. biflorus administration to high fat diet fed rats showed near to normal levels
      of the above lipids in plasma and tissues. Higher dose of the extract (400 mg/kg
      body weight) showed comparable results with standard drug atorvastatin. It is
      concluded that the methanolic extract of D. biflorus possesses hypolipidemic
      activity in high fat diet fed rats.

PMID- 15991578
TI  - Effect of pretreatment of Cassia fistula Linn. leaf extract against subacute CCl4
      induced hepatotoxicity in rats.
AB  - CCl4 alone treatment (0.lml of liquid paraffin/100g body weight, ip) for 7 days
      followed by 0.l ml of CCl4 (in liquid parafiin/100g body weight, ip) from day 8
      till day 14, caused a 16 fold increase in lipid peroxidation and a 50% reduction
      in catalase and glutathione reductase in liver tissue of rats accompanied by an
      increase in the activities of transaminases. alkaline phosphatase, lactate
      dehydrogenase and gamma - glutamyl transpeptidase in serum as compared to liquid
      paraffin treated control. Pretreatment of ethanolic leaf extract of C. fistula
      (500mg/kg body weight/day for 7 days) followed by CCl4 treatment (0.1 ml/100g
      body weight from day 8 till day 14) completely reversed back lipid peroxidation
      and the activities of catalase and glutathione reductase in the liver tissue
      towards normalcy. This treatment also reversed the elevated levels of the enzymes
      in the serum. Ethanolic leaf extract alone treatment did not produce any change
      in all the parameters studied. The results suggest antioxidant and
      hepatoprotective properties of C. fistula during its pretreatment against CCl4
      induced hepatotoxicity.

PMID- 15991579
TI  - Comparative diagnostic potentiality of ELISA and dot-ELISA in prepatent diagnosis
      of experimental Fasciola gigantica infection in cattle.
AB  - A glycoprotein (27 kDa) was isolated from crude somatic antigen of Fasciola
      gigantica by two steps affinity chromatography and was used in early detection of
      experimental fasciolosis in cattle by indirect ELISA and in dot-ELISA formats.
      Although, anti-27 kDa antibodies could be detected after 3 weeks post infection
      (WPI) by dot - ELISA which was one week later than indirect ELISA. The test, dot
      ELISA, was more convenient in field application. By the test (dot-ELISA) the
      infection could be equally detected in animals infected with 100, 200 and 300
      metacercariae of F. gigantica with high sensitivity. Further, the antigen (27
      kDa) was not found to react with goat sera infected with Paramphistomum
      epiclitum, which are giving strong reaction to homologous immature and mature
      fluke antigens of P. epiclitum.

PMID- 15991580
TI  - Alcaligenes faecalis kw-a biofilm for denitrification of nitrate-rich effluent.
AB  - Alcaligenes faecalis kw-A selected for possessing good denitrification efficiency
      was used for biofilm development. The biofilm could be developed on a glass
      surface within 12 hr when 5%, Ix 10(8) cells/ml was used as inoculum. The
      microcolonies were seen in 6 hr and glycocalyx in 9 hr stage. At 24 hr the
      biofilm was developed fully and hence was visualised as dense mass. The biofilm
      protein content showed 48.5% increase in shake flask than in static condition.
      The exopoplymer is produced in larger amounts in biofilm as compared to the
      suspended cells. Also, its amount was more by 43% in the biofilm produced in
      shake flask condition than in static condition. The biofilm could remove 95%
      nitrate from nitrate-rich effluent in a bench-scale process in 36 hr. The
      attached growth technique demonstrated here can be utilised to study the effect
      of favourable as well as adverse conditions on the denitrification efficiency of
      a culture. The ultimate application of a denitrifying biofilm would be in
      attached growth or biofilm reactor.

PMID- 15991581
TI  - Detection of genetic polymorphism in the populations of brinjal shoot and fruit
      borer, Leucinodes orbonalis (Guenee).
AB  - In the present study six different populations of L. orbonalis were collected and
      subjected to analysis of genetic variability in terms of carboxylesterase isozyme
      pattern and DNA polymorphism using RAPD-PCR. Pattern of carboxylesterase revealed
      a similar isozyme cluster in the populations namely, sivaganga (population-3),
      dindigal (population-4), virudhunagar (population-5) and coimbatore (population
      6). Similarly, the populations of L. orbonalis recorded 3 distinct randomly
      amplified polymorphic DNA markers in all populations grouped above. This pattern
      of genetic variability in the populations was also supported by the analysis of
      the similarity indices and UPGMA dendrogram.

PMID- 15991582
TI  - In vitro response of encapsulated somatic embryos of Lagerstroemia indica L.
AB  - A method to produce encapsulatable units for synthetic seeds was developed in L.
      indica. Somatic embryos were harvested from leaf derived embryogenic callus on
      Murashige and Skoog's basal medium supplemented with 2, 4-dichlorophenoxy acetic
      acid (2, 4-D, 0.5 mg/l), 6-benzyl amino purine (BAP, 1 mg/l) and ascorbic acid
      (AA, 50 mg/l). The embryos were encapsulated in alginate beads and dehydrated.
      Germination ability of the artificial seeds were investigated. The frequency of
      regeneration from the encapsulated embryos was significantly affected by (i) the
      concentration of alginate (ii) the duration of storage, and (iii) the effect of
      different types of media. A 2% sodium alginate concentration on MS salts resulted
      in significantly higher germination frequencies than at other concentrations. L.
      indica showed maximum germination on MS medium (93.84%) after 6 weeks of culture.
      The germinated synthetic seeds with well developed roots and shoots were
      transferred successfully to green house. This is the first report on artificial
      seeds in Lagerstroemnia indica.

PMID- 15991583
TI  - Biochemical studies of embryogenic and non-embryogenic callus of Cardiospermum
      halicacabum L.
AB  - Some physiological and biochemical changes were measured between embryogenic and
      non-embryogenic callus obtained from Cardiospermum halicacabum. Combination of
      auxin with cytokinin was more favourable for high amount of callus formation. 2,4
      D played a key role in triggering somatic embryo formation. Embryogenic callus
      had more total carbohydrate and starch contents, total free amino acids, nucleic
      acids, phenols and ascorbic acid. Non-embryogenic callus exhibited high
      chlorophyll content, total soluble sugar, protein, ammonia and enzymes like
      peroxidase and polyphenol oxidase. Thus, the present study indicated that the
      process of somatic embryogenesis was characterized by some biochemical and
      physiological changes induced by plant growth regulators.

PMID- 15991584
TI  - In vitro clonal multiplication of an apple rootstock by culture of shoot apices
      and axillary buds.
AB  - In vitro clonal multiplication of apple rootstock MM 111 using axillary buds and
      shoot apices were carried out. Vegetative axillary buds of the size of 0.2-2.0 cm
      and shoot apices measuring 4 mm in length were initiated to shoot proliferation
      on MS medium supplemented with BA (0.5 - 1.0 mgl(-1)), GA3(0.5 mgl(-1)), with or
      without IBA(0.05 - 0.1 mgl(-1)). Small size explants showed less phenol exudation
      and less contamination. Following establishment phase, the small shoots emerged
      from explants were subcultured on MS medium supplemented with different
      combinations and concentrations of growth regulators. BA (1.0 mgl(-1)) and GA3
      (0.5 mgl(-1)) combination showed highest multiplication rate (1:5), andcl also
      produced longer shoots. Two step rooting was done by transferring microcuttings
      to auxin free solid medium after root initiation in dark on 1/2 strength MS
      liquid medium containing IBA (0.5 mgl(-1) ). Rooted plantlets were transferred to
      peat containing paper cups and resulting plants of MM 111 acclimated successfully
      for transfer to field.

PMID- 15991585
TI  - Effect of Mesua ferrea Linn. flower extract on Salmonella.
AB  - Based on its traditional uses in folk medicine, the whole flower extract of Mesua
      ferrea Linn. was tested for its in vitro antimicrobial efficacy against five
      different strains of Salmonella spp. All the strains were found to be highly
      sensitive to the extract, MIC of the extract against each organism being 50
      microg/ml. The extract was tested in vitro for its mode of antibacterial activity
      against S. Typhimurium NCTC 74 and it was found to be bactericidal in action. In
      vivo studies of this extract offered significant protection to Swiss albino mice
      at doses approximately 2 and 4 mg/mouse when challenged with 50 median lethal
      dose of S. Typhimurium NCTC 74. Further, the extract caused statistically
      significant reduction in viable count of the strain in liver, spleen and heart
      blood of challenged mice.

PMID- 15991586
TI  - The ASAM patient placement criteria: context, concepts and continuing
      development.

PMID- 15991587
TI  - Determining service variations between and within ASAM levels of care.
AB  - The American Society of Addiction Medicine (ASAM) Criteria Validity Study at
      Massachusetts General Hospital and Harvard Medical School randomized patients
      between programs in two levels of care. It therefore became critical to determine
      the extent to which programs met ASAM level of care (LOC) descriptions.
      Quantitative surveys (checklist) and qualitative case studies (field observation,
      key informant interviews) documented care variation within and between two ASAM
      LOCs in 12 substance abuse treatment units. These LOCs were: Level II (Intensive
      Outpatient Treatment) and Level III (Medically Monitored Residential Treatment).
      The Level II and Level III programs, as a group, met ASAM LOC criteria, but data
      showed major within-level variation by hours per day and number and type of
      skilled treatment services. Observational data suggest considerable within-level
      variation due to managed care and staff training. In multi-site PPC validity
      studies, it will be crucial to examine within-LOC variation and take into account
      payment sources and staff training when assessing patient outcomes.

PMID- 15991588
TI  - Impact of patient placement criteria on substance abuse treatment under the
      Oregon Health Plan.
AB  - When Oregon shifted to managed care for Medicaid-funded substance abuse
      treatment, standardized patient placement and discharge criteria were rapidly
      implemented statewide. This prospective, naturalistic study examines the validity
      and impact of placement criteria with a sample of 240 adults presenting for
      treatment compared to a sample of 287 in Washington state, where implementation
      was phased in slowly. Baseline profile analysis suggested better differentiation
      between Level II and Level III clients for the Oregon sample and better
      implementation than with the Washington sample, presumably because Oregon
      clinicians received more training and had more experience with the criteria. A
      majority of the Oregon sample was placed in intensive outpatient programs,
      consistent with the recommended level of care. In this study, placement criteria
      showed good potential for changing treatment planning behavior, increasing
      individualization, and improving utilization of new levels of care.

PMID- 15991589
TI  - Reliability of multidimensional substance abuse treatment matching: implementing
      the ASAM Patient Placement Criteria.
AB  - For meaningful adoption, the Patient Placement Criteria (PPC) of the American
      Society of Addiction Medicine (ASAM) will need adequate interrater reliability.
      In a decision analysis of the original PPC, we reduced potential sources of
      unreliability, mapped question items from clinical research instruments to each
      decision point, and programmed the item map as a computerized structured
      interview. Then, target videotapes from eight substance dependent adults who had
      been distributed by the algorithm into three levels of care (LOC) were
      independently scored by four raters who were blind as to ASAM LOC. The intraclass
      correlation coefficient for ASAM LOC assignment was .77. For all but two
      subscales of component instruments, values were above .70 and significant,
      indicating high interrater reliability. With these methods, excellent reliability
      is possible for complex decision trees, making it possible to improve the
      validity of the ASAM Criteria and similar complex hierarchical clinical
      protocols.

PMID- 15991590
TI  - Convergent validity of the ASAM Patient Placement Criteria using a standardized
      computer algorithm.
AB  - The study examined the convergent validity of the ASAM Patient Placement Criteria
      (PPC) by comparing Level of Care (LOC) recommendations produced by two
      alternative methods: a computerdriven algorithm and a "standard" clinical
      assessment. A cohort of 248 applicants for alcoholism treatment were evaluated at
      a multi-modality treatment center. The two methods disagreed (58% of cases) more
      often than they agreed (42%). The algorithm recommended a more intense LOC than
      the clinician protocol in 81% of the discrepant cases. Four categories of
      disagreement accounted for 97% of the discrepant cases. Several major sources of
      disagreement were identified and examined in detail: clinicians' reasoned
      departures from the PPC rules, conservatism in algorithm LOC recommendations, and
      measurement overlap between two specific dimensions. In order for the ASAM PPC
      and its associated algorithm to be embraced by treatment programs, the observed
      differences in LOC recommendations between the algorithm and "standard" clinical
      assessment should be resolved.

PMID- 15991591
TI  - Predictive validity of the ASAM Patient Placement Criteria for hospital
      utilization.
AB  - We tested the validity of the ASAM Patient Placement Criteria (PPC) using the
      first complete and reliable computerized implementation of these criteria. Adult
      U.S. veterans (N = 95) seeking substance abuse treatment were blindly assessed
      for level of care need according to the PPC but were naturalistically assigned by
      counselors to residential rehabilitation (Level III) without knowledge of the PPC
      recommendation. Analyses compared subjects across three levels of recommended
      care, based on the algorithm, for utilization outcomes of VA hospital admissions
      and bed days of care. Subjects who were mismatched to lesser level of care than
      recommended utilized nearly twice as many hospital bed-days over the subsequent
      year (F (2;92) = 3.88; p < .05); this was unrelated to differential pre
      assessment chronicity. The computerized algorithm is a promising new tool for
      facilitating field trials of the validity of the ASAM Criteria. A comprehensive
      implementation is an important methodologic requirement. These preliminary
      results support predictive validity for the ASAM Criteria, in that mismatching
      may be associated with excessive hospital utilization.

PMID- 15991593
TI  - Development of service intensity criteria and program categories for individuals
      with co-occurring disorders.
AB  - Many patients present a clinical situation in which psychiatric symptomatology
      and substance related symptomatology are inextricably intertwined. A paradox
      exists for these patients, in that both the addictions and mental health systems
      of care, and the level of care assessment methodologies associated with each
      system, are designed for one type of disorder only, or only one disorder at a
      time. As a result, these individuals are perceived as "system misfits." Our
      inability to assess these patients accurately and place them appropriately
      contributes to poor outcomes and high costs. These costs consist of expensive
      utilization of scarce system resources. There is a growing need for a more
      integrated methodology for level of care assessment, in which both psychiatric
      and substance symptomatology can be assessed simultaneously to generate a wider
      array of programmatic interventions for individuals with co-occurring disorders.
      This article describes efforts to build upon the Patient Placement Criteria
      published by the American Society of Addiction Medicine, Second Edition (ASAM PPC
      2) to develop a revised instrument that is much more capable of evaluating the
      placement needs of individuals who present with combinations of psychiatric and
      substance symptomatology.

PMID- 15991592
TI  - New constructs and assessments for relapse and continued use potential in the
      ASAM Patient Placement Criteria.
AB  - One area of intensive study in recent years in addiction research is the
      characterization and prediction of relapse risk. Given the growing list of
      findings and assessment tools in this area, in preparation for the second
      edition, revised volume of the Patient Placement Criteria (PPC) of the American
      Society of Addiction Medicine (ASAM), a workgroup of the Coalition for National
      Criteria was assigned the task of creating a revised conceptual organization for
      Dimension 5: Relapse/Continued Use Potential. The workgroup conducted a review of
      the previous Dimension 5 constructs and criteria, including a decision analysis
      of the previous Dimension 5 decision rules. Following that analysis, field data
      from the ASAM Criteria Validity Study at Massachusetts General Hospital and
      Harvard Medical School were analyzed from a large cohort of public and indigent
      patients in eastern Massachusetts. After determining the concurrent validity of
      the Dimension 5 decision rules and their limitations, the decision rules were
      rewritten to gain improved validity. This exercise revealed techniques that can
      and should be used to improve the discrimination of levels of care among all
      Dimensions. Finally, the workgroup expanded and refined the constructs that
      should comprise a revised Dimension 5. This revised list of constructs is
      sequential and hierarchical. It offers face validity on several levels of current
      basic and clinical research knowledge: behavioral pharmacology, behavioral
      psychology, learning theory and psychopathology. While the Second Edition-Revised
      volume of the ASAM PPC (PPC-2R) does not go so far as to propose final decision
      rules for Dimension 5 based on these new constructs, it does recommend pilot
      adoption of several new assessment tools for this dimension and provides the
      framework incorporating those constructs and assessments in the next complete PPC
      edition.

PMID- 15991594
TI  - [Lectures and laboratory training in education of physiology].

PMID- 15991595
TI  - [Cardiac pacemaker].

PMID- 15991596
TI  - Studies on post-transplant dyslipidemia in kidney transplant patients.
AB  - This study was performed to retrospectively compare changes in the levels of
      total cholesterol, non-HDL cholesterol, triglycerides, and immunosuppressive
      drugs, cyclosporine A and steroids in patients with living-relation renal
      transplants with those from non-heart-beating donors. We experienced 11 cases of
      kidney transplants from non-heart-beating donors during the period from April
      1995 to May 2003. We evaluated 13 cases of kidney transplants from living
      relation donors during the same period. The immunosuppressants used included
      mainly cyclosporine A as well as mycophenolate mofetil or azathioprine, steroid
      and ALG, or basiliximab. Over-night fasting lipids (total cholesterol,
      triglycerides and HDL cholesterol) were studied before renal transplantation and
      repeated after renal transplantation at 1, 3, 6 and 12 months. The levels of
      total cholesterol and triglycerides remained in the normal range before
      transplantation. However, the levels of total cholesterol increased
      siginificantly 1 and 3 months after transplantation from non-heart-beating donors
      and remained at higher levels up to 12 months after transplantation. A similar
      pattern in the levels of triglycerides was observed. The levels of HDL
      cholesterol remained unchanged and stayed in the normal range before and 1, 3, 6,
      and 12 months after transplantation from non-heart-beating donors. On the other
      hand, significant increases in non-HDL cholesterol were observed 3 and 6 months
      after transplantation from non-heart-beating donors. After transplantation from
      living-relation donors, levels of total cholesterol, triglycerides, and non-HDL
      cholesterol remained unchanged and remained in the normal range up to 12 months
      after transplantation. Although there were no significant differences in the
      total dosage of cyclosporine A between the patients with living-relation donors
      and those with non-heart-beating donors, a significant increase in the total
      dosage of methylprednisolone was observed in patients with non-heart-beating
      donors compared with those in the patients with living-relation donors. Renal
      function recovery in patients with living-relation donors was better than in
      those with non-heart-beating donors. These results may suggest that significant
      increases in total cholesterol, especially non-HDL cholesterol and triglycerides,
      were probably partly due to an increased use of immunosuppressants, steroids. It
      is necessary to aggressively control post-transplant hyperlipidemia and important
      to reduce or withdraw steroids in the selected, low-risk recipients as early as
      possible from the viewpoint of preventing post-transplant hyperlipidemia.

PMID- 15991597
TI  - A five-year review of patients admitted with the diagnosis of bacterial
      endophthalmitis.
AB  - We conducted a retrospective, hospital-based study of patients who were diagnosed
      with bacterial endophthalmitis on admission to the Department of Ophthalmology,
      Hiroshima University Hospital, between January 1999 and December 2003. Thirty
      eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative
      endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an
      endogenous source. All of the patients underwent immediate three-port pars plana
      vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly
      higher incidence of positive bacterial culture. Diabetic vitreous appeared to be
      a good medium for culture. Visual acuity of hand motion or less at the latest
      follow-up visit was associated with the presence of diabetes. Prompt treatment
      with vitrectomy and intra-vitreal antibiotics is crucial for patients with
      bacterial endophthalmitis, especially if they are diabetic.

PMID- 15991598
TI  - Reconstruction of pterional key hole using three-dimensional titanium plate:
      technical note.
AB  - Patients who have undergone pterional craniotomy sometimes complain about
      postoperative cosmetic impairment in the frontotemporal area. This problem occurs
      as a result of inappropriate repair or no repair of the pterional key hole. The
      authors have developed an intraoperative hand-made three-dimensional titanium
      plate, and as a result of using this plate the postoperative cosmetic appearance
      was satisfactory.

PMID- 15991599
TI  - Traumatic lumbar fracture-dislocation related to spina bifida occulta: case
      report.
AB  - Traumatic lumbar fracture-dislocation is a rare condition. Congenital spinal
      deformities may facilitate the occurrence of this case. We diagnosed spina bifida
      occulta accompanied at the same level by a L2 anterior dislocation which resulted
      from a vehicle in-site traffic accident in a 35-year-old female patient.
      Posterior intervention was carried out during therapy, and reduction and
      stabilization were performed by means of a T12-L1 and L2-L3 trans-pedicular
      screw. In patients with a congenital spinal anomaly the effect of spinal traumas
      may be greater than normal. Therefore, spinal traumas in patients with a
      congenital spinal anomaly should be assessed more carefully.

PMID- 15991601
TI  - [A rare case of disseminated Mycobacterium kansasii infection].
AB  - Mycobacterium kansasii infection has been reported to be about 20 percent of non
      tuberculous mycobacteriosis, and its disseminated type is uncommon and the
      prognosis is reported to be generally poor. We experienced one case of
      disseminated Mycobacterium kansasii infection. A 81 year-old man who had been
      short-bowel syndrome due to the operation for superior mesenteric artery
      occlusion since 1998 was admitted on April 24th, 2001 to our hospital because of
      slowly progressive consciousness disturbance and anorexia. He had shown
      progressive productive cough and respiratory failure and laboratory findings were
      C-reactive protein elevation and pancytopenia. Human immunodeficiency virus (HIV)
      antibody was negative. Chest X-ray and computed tomography showed diffuse miliary
      nodules and infiltrative shadow. Sputum examination was positive for
      mycobacteria. The cultured isolate was identified as Mycobacterium kansasii. Bone
      marrow aspirations revealed inflammatory granuloma with necrosis. He was
      diagnosed as disseminated Mycobacterium kansasii infection and heart failure, and
      was treated by anti-tuberculosis drugs and diuretics. Treatment was very
      effective and Chest X-ray findings and respiratory failure had been completely
      improved. In this case we speculated that the malnutrition due to short-bowel
      syndrome could be one of the most suspected reasons of Mycobacterium kansasii
      dissemination. Disseminated Mycobacterium kansasii infection has been rarely
      reported comparing with the other mycobacterial infections in Japan. However, due
      to the increasing numbers of immunocompromised hosts with aging, HIV infection,
      cancer, and steroid therapy, this type of infection will become more common and
      its earlier diagnosis and adequate treatment will be important to improve the
      prognosis.

PMID- 15991600
TI  - [The external quality assessment for Mycobacterium tuberculosis drug
      susceptibility testing by proficiency testing panel to the commercial
      laboratories].
AB  - OBJECTIVE: The Committee for Mycobacterial Examinations has programmed and
      implemented the external quality assessment for Mycobacterium tuberculosis drug
      susceptibility testing by proficiency testing panel to the commercial
      laboratories that perform drug susceptibility testing more than 20 cases monthly.
      METHOD: It utilized 20 strains, exactly pairs of 10 strains, of Mycobacterium
      tuberculosis that were evaluated for the resistance pattern in the WHO/IUATLD
      supra-national laboratory network (SRLN), and the concordant results within SRLN
      were employed as the gold standard of the test. Each laboratory performed the
      drug susceptibility testing with routine method including the preparation of
      bacterial suspension. RESULTS: As a result, the sensitivity for isoniazid (INH)
      was 95% on an average, ranging from 29% to 100%. The specificity and efficiency
      for INH were 100% and 97% (50-100), respectively. Additionally, the
      reproducibility for INH was 99% (90-100). Similarly, the sensitivity,
      specificity, efficiency and reproducibility for rifampicin (RFP) were 95% (63
      100), 99% (67-100), 97% (70-100) and 98% (90-100), respectively. The sensitivity,
      specificity, efficiency and reproducibility for streptomycin (SM) were 66% (33
      100), 94% (64-100), 86% (65-100) and 96% (80-100), respectively. For EB, the
      sensitivity, specificity, efficiency and reproducibility were 96% (33-100), 74%
      (57-86), 81% (60-90) and 96% (80-100), respectively. DISCUSSION: The required
      standard for satisfactory results of sensitivity, specificity and reproducibility
      is 95%, and the results for INH and RFP were excellent on an average. However,
      several laboratories showed unsatisfactory results, especially in sensitivity.
      Almost all the discordant results for INH and RFP were false-susceptible
      comparing to the gold standard. For INH, one pair of tested strain showed
      discordant results in many evaluated laboratories and seemed to reflect the
      relatively low concordance even in SRLN. On the other hand, the reason for false
      susceptible results for RFP was unclear. Several laboratories showed discordant
      results in one strain pair so that it might be a technical mistake. The
      sensitivity of SM was remarkably low and it was due to many false-susceptible
      results, which was twice the number of false-resistance. It was due to the
      character of tested strain partially considering relatively low concordance in
      SRLN. However, there was no persuasive explanation for the inconsistency in other
      strains that showed highly concordant results in SRLN. The difference of critical
      drug concentration in Lowenstein-Jensen and 1% Ogawa medium might contribute to
      the discrepancies. The specificity of EB was low and it was due to many false
      resistant results. About a specific pair of tested strain, almost 100% of
      laboratories showed concordant false-resistant results whereas SRLN showed
      perfectly concordant susceptible result. If this strain was considered as
      resistant and another strain that showed less than 70% concordance in the tested
      laboratories was excluded, the sensitivity, specificity and efficiency would
      improve to 96%, 97% and 97%, respectively. The proficiency testing is a part of
      external quality assessment system and requires following corrective actions. A
      permanent quality improvement and maintenance will be expected through the spiral
      circulation of quality assurance activities.

PMID- 15991602
TI  - [Reinfection of tuberculosis in HIV-negative persons].
AB  - To clarify our knowledge about exogenous reinfection of Mycobacterium
      tuberculosis in HIV-negative persons, we review the literatures on this issue as
      much as possible, and we deduce the following; 1) Risk of exogenous reinfection
      may be not rare in itself, but quantifiably determined by host factor, bacilli
      factor and intensity of exposure. 2) Generally, when already-infected persons are
      exposed to exogenous reinfection Mycobacterium tuberculosis, risk of disease due
      to the exposure is definitely lower than not-already-infected persons (estimated
      relative risk: 8.5%). But the protection rate can be similar with that of BCG
      vaccination under most favorable condition. 3) It cannot be concluded definitely
      that the tuberculosis disease in already-infected persons is almost always due to
      endogenous reactivation.

PMID- 15991603
TI  - [Usefulness of support during treatment by alignment with health centers and DOT
      during hospitalization].
AB  - OBJECTIVES: To evaluate the effectiveness of patient support by alignment with
      public health centers and DOT during hospitalization, on treatment completion of
      tuberculosis patients. SUBJECTS: Four hundred seventy-seven patients (male 344,
      female 133) newly admitted from July 1, 2002 to June 30, 2003 to our hospital
      were enrolled in the study. METHOD: The patients were divided into two groups:
      one comprised of the patients who were discussed in the conference held by the
      hospital staffs and the regional public health center staffs about the necessity
      of support for continuing treatment regularly after discharge from our hospital
      (Conference (+) group; N=306), and the other who were not discussed in the
      conference (Conference (-) group; N=171). The Conference (+) group was further
      divided into two groups: One comprised of the patients who were regarded to need
      support after discharge (Support (+) group; N=106), and the other no need of
      support after discharge (Support (-) group; N=200). The patients' characteristics
      and backgrounds were compared between the Conference (+) and the Conference (-)
      groups, and between the Support (+) and the Support (-) groups. The rate of
      treatment completion and of default were compared between the Conference (+) and
      the Conference (-) group, and between the Support (+) and the Support (-) group.
      They were also compared between the patients with and without DOT for a month
      during hospitalization, and between the patients who were treated for the first
      time (new case) and those who had been treated previously (retreated case) or who
      had been treated when they were admitted to our hospital and continued treatment
      after admission (continuous cases). RESULTS: There is no significant differences
      in patients' characteristics and backgrounds between the Conference (+) and
      Conference (-) groups, but the ratios of male, sputum-culture positivity, far
      advanced lesions on chest X-ray, hypoalbuminemia, and disemployment were higher
      in Support (+) group than in Support (-) group. The overall (N=477) treatment
      outcomes were as follows: cured (defined by sputum-culture negativity at
      completion of chemotherapy) 300 (62.9%), completed (defined by no sputum data at
      completion of chemotherapy) 90 (18.9%), failed 5 (1.0%), defaulted 6 (1.3%),
      transfer out 6 (1.3%) and death 70 (14.7%). Therefore, the ratio of treatment
      success (defined by cured+completed) was 390/477 (81.8%). Because of more died
      cases in Conference (-) groups, treatment success rate was significantly higher
      in the Conference (+) groups than in the Conference (-) groups. There were no
      significant differences in the rate of treatment success and of default between
      the Support (+) and the Support (-) groups, but no defaulter case was seen in the
      Support (+) group. There were no differences in the rate of treatment success and
      of default between the groups with and without DOT for a month during
      hospitalization. There were no differences in the rate of treatment success and
      of default between the groups with the retreated and continuously treated cases
      and the new cases. CONSIDERATIONS: Treatment success rate was excellent in our
      study. DOT for a month during hospitalization didn't affect the improvement of
      treatment success after discharge, partly because the education on tuberculosis
      treatment was sufficiently done for most patients during hospitalization and a
      nurse made a telephone call to the patient who didn't attend the outpatient
      department of the hospital. CONCLUSIONS: To hold conference with regional public
      health center is effective for completion of tuberculosis treatment.

PMID- 15991604
TI  - [Comedical education and its role in clinical medicine -from Nitingale to Vivien
      Thomas].

PMID- 15991605
TI  - [B cells as key contributors in determining the level of immune responses -B-cell
      targeted therapy in patients with autoimmune diseases].
AB  - The levels and types of immune responses are determined dependent on the extent
      of pathogen invasion, reactions to antigens mediated by macrophage-dendritic
      cells, T cells and antibodies. Recently, accumulating evidence suggests that B
      cells also play an important role in the regulation of immune responses. Here we
      have made a review to present a role of B cells in determining the level of
      immune responses and discussed about the clinical significance of B cell-targeted
      therapy in patients with autoimmune diseases. Type 1 diabetes is a T cell
      mediated autoimmune disease characterized by the destruction of insulin-producing
      pancreatic beta cells. We and other groups have elucidated that B cells play a
      critical role in the development of insulitis and diabetes, as B-cell-deficient
      NOD mice are protected from developing type 1 diabetes. B cells are essential for
      the T cell receptor clonotype spreading of islet-infiltrating T cells, indicating
      that B cells may play a role in determining the level of immune responses by
      antigen presentation to antigen specific T cells. There are now numerous case
      reports and small series of clinical trials regarding rituximab therapy in
      autoimmune diseases, such as refractory autoimmune hemolytic anemia, IgM antibody
      associated polyneuropathy, systemic lupus erythematosus and rheumatoid arthritis.
      Rituximab is a genetically engineered chimeric anti-CD 20 monoclonal antibody
      that is approved for the treatment of lymphoma. CD20 is a B-cell surface antigen
      that is expressed only on pre- B and mature B cells. Thus, rituximab causes a
      selective transient depletion of the CD20+ B -cell subpopulation. Rationale and
      strategy for targeting B cells in the treatment of autoimmune diseases consist of
      the inhibition of antigen-presentation and co-stimulation that induces T cell
      expansion and activation. Further careful mechanistic studies are required to
      develop therapies in patients with autoimmune diseases.

PMID- 15991606
TI  - Percutaneous vertebroplasty in the treatment of pain caused by metastatic tumor.
AB  - Percutaneous vertebroplasty is a radiologically guided therapeutic procedure that
      consists of percutaneous injection of polymethylmetacrylate (PMMA) into
      pathologic vertebral bodies. It is a minimally invasive procedure that is
      effective in the treatment of pain resulting from bone metastasis. This procedure
      has the advantage of providing rapid pain relief and spinal stabilization. A
      patient with severe, aggressive pain from metastatic lumbar spinal tumor of
      thyroid follicular carcinoma is presented herein. Despite treatment with
      analgesic agents, external beam radiation therapy, radioiodine therapy, and
      posterior fusion surgery, the pain reemerged and progressed. After percutaneous
      vertebroplasty, definite pain relief was achieved. Vertebroplasty would be useful
      as an additional or alternative pain relief method in patients with metastatic
      vertebral tumors.

PMID- 15991607
TI  - Atrial septal pacing to resynchronize atrial contraction and improve atrial
      transport function.
AB  - OBJECTIVES: Atrial septal pacing via a trans-septal breakthrough site within the
      right atrial septum can shorten global atrial activation time, resulting in
      significant reduction of recurrence of atrial fibrillation events. This study
      examined whether this pacing method will lead to resynchronization of atrial
      contraction and its benefit on hemodynamic function can be maintained for 24
      months. METHODS: Thirty patients with atrial fibrillation and delayed atrial
      conduction were enrolled (17 males, 13 females, mean age 73 +/- 7 years). Trans
      septal breakthrough site within the right atrial septum was identified through
      pacing from the dorsal left atrium. Continuous atrial septal pacing at the trans
      septal breakthrough site was performed for 24 months. Time difference (TD)
      between right and left atrial contractions was measured during atrial septal
      pacing and sinus rhythm by pulse Doppler echocardiography of the trans-tricuspid
      (P-At) and mitral (P-Am) blood flows (TD = P-Am - P-At). RESULTS: The atrial lead
      was screwed near the fossa ovalis in 29 of 30 patients. Atrial septal pacing
      yielded significantly shorter P wave duration (101.9 +/- 10.4 vs 139.6 +/- 14.7
      msec, p < 0.001), leading to significant reduction of TD in atrial contraction (
      8.8 +/- 10.0 vs 29.8 +/- 13.6 msec, p < 0.001)as compared to sinus rhythm. Both
      shorter P wave duration and reduced TD during atrial septal pacing remained
      statistically significant during the follow-up period as compared to sinus
      rhythm. Both left atrial diameter and A to E ratio of filling waves at mitral
      valve were significantly decreased at 12 months and remained decreased at 24
      months. CONCLUSIONS: Atrial septal pacing at the trans-septal breakthrough site
      can resynchronize atrial contraction and results in improved hemodynamic effects
      during 24 months of follow-up.

PMID- 15991608
TI  - [Effects of immunoglobulin on murine myocarditis caused by influenza A virus:
      experimental study].
AB  - OBJECTIVES: Influenza A viruses play the largest role in the worldwide
      epidemiology of infectious diseases. We examined the effects of intact type and
      F(ab')2 type of immunoglobulin preparations on murine influenza A virus
      myocarditis in mice. METHODS AND RESULTS: In vitro study showed that intact type
      and F(ab')2 type of immunoglobulin preparations had antiviral activities against
      many substrains of influenza A virus and other cardiotropic viruses, and that
      dose-dependent suppression of an influenza A virus (NWS type) was demonstrated by
      the treatment of both intact immunoglobulin and F(ab')2 fragments of
      immunoglobulin. The dose inhibiting 50% of plaques was same between intact type
      and F(ab')2 type (both 0.0002 mg/dl). Intact immunoglobulin, but not F(ab')2
      fragments of immunoglobulin, suppressed serum macrophage inflammatory protein-2
      (MIP-2) production in influenza A virus infected macrophages in vitro, which is a
      murine counterpart of interleukin-8. This suppression of MIP-2 production by
      intact immunoglobulin treatment was blocked by a specific Fc receptor (Fc gamma
      III/II receptor) antibody pretreatment. Intact immunoglobulin (1 g/kg/day) or
      F(ab')2 fragments of immunoglobulin (1 g/kg/day) were administered to the virus
      inoculated A/J mice intraperitoneally daily, starting simultaneously with virus
      inoculation (Experiment I ) and 2 days after the virus inoculation (Experiment II
      ), until 10th days after virus inoculation. In Experiment I, survival was higher
      in treated [intact (100%, 20/20), and F(ab')2 (100%, 20/20)] than in control
      (25%, 5/20) mice; intact type and F(ab')2 type immunoglobulin administration
      completely suppressed the development of myocarditis. In Experiment II, survival
      rate was significantly higher (75%, 15/20) and myocarditis was less severe in
      intact immunoglobulin treated mice, but not in F(ab')2 fragment treated mice
      (60%, 12/20), than in untreated mice (35%, 7/20). Serum neutralizing antibody
      titers in treated mice were significantly higher compared with untreated mice in
      Experiments I and II. In addition, serum MIP-2 concentrations in intact
      immunoglobulin treated mice, but not in F(ab')2 fragments treated mice, were
      lower compared with untreated mice in Experiment II. Immunoglobulin therapy
      suppresses influenza A virus myocarditis by increasing neutralizing antibody
      titers and the suppression of myocardial virus activities. From the stand-point
      of suppression of MIP-2 concentrations, intact type is superior to F(ab')2 type.
      CONCLUSIONS: Immunoglobulin treatment may be promising for the prevention of
      influenza A virus myocarditis.

PMID- 15991610
TI  - [Deep vein thrombosis caused by pelvic lymphocyst following radical
      prostatectomy: a case report].
AB  - A 66-year-old man was admitted with distal edema of his right leg. He had
      undergone radical prostatectomy and pelvic lymphadenectomy for prostatic cancer
      23 days previously. Abdominal computed tomography (CT) showed a lymphocyst (4.5 x
      3.0 cm) along the right pelvic wall compressing the right external iliac vein. CT
      with contrast medium showed thrombus formation (about 9 cm) in the distal portion
      of the right external iliac vein and femoral vein. An inferior vena cava filter
      was placed to prevent pulmonary embolism, and anticoagulation with warfarin was
      started. One week later, CT showed shrinkage of the lymphocyst and thrombus in
      the vein, as well as a large thrombus trapped in the filter. Follow-up CT taken 2
      months later revealed marked reduction of the lymphocyst and absence of thrombus
      in both the vein and filter. A lymphocyst, also known as a lymphocele, is a
      complication of radical pelvic surgery. Most lymphocysts are asymptomatic and
      regress spontaneously, but may lead to deep vein thrombosis and pulmonary
      embolism, usually a few weeks after surgery. Careful observation is needed even
      after discharge from hospital.

PMID- 15991609
TI  - Successfully treated triple valve infective endocarditis: a case report.
AB  - A 45-year-old woman presented with triple valve infective endocarditis and
      ventricular septal defect. There were vegetations on the tricuspid valve,
      pulmonary valve, and aortic valve. She had multiple complications such as
      nephrotic syndrome, severe anemia, congestive heart failure, and convulsion. Her
      general condition was extremely poor. Intensive medical therapy, such as blood
      transfusion, mechanical ventilation, and continuous venovenous hemofiltration,
      allowed her to tolerate surgery. Triple valve replacement and ventricular septal
      defect closure was successfully performed without major complication. She was
      ambulatory at the time of discharge.

PMID- 15991611
TI  - [Coronary sinus ostial atresia with thrombus: a case report].
AB  - An 82-year-old woman presented with mitral regurgitation and atrial fibrillation.
      She was hospitalized for further examination of cardiac thrombus detected by
      transthoracic echocardiography. No definitive diagnosis could be made based on
      computed tomography and magnetic resonance imaging. Intravenous contrast
      echocardiography suggested a coronary sinus thrombus. Coronary angiography showed
      coronary sinus ostial atresia. Multislice computed tomography confirmed the
      presence of thrombus in the enlarged coronary sinus with coronary sinus ostial
      atresia and persistent left superior vena cava. Persistent left superior vena
      cava is present in 3% of patients with congenital heart disease. Persistent left
      superior vena cava is detected by chance during cardiac catheterization for other
      conditions in patients without cardiac malformations. The present case was
      detected at an advanced age, and in the absence of prior symptoms.

PMID- 15991612
TI  - Reduced left ventricular ejection fraction in an 82-year-old woman with aortic
      stenosis.

PMID- 15991613
TI  - [Atrial fibrillation and anticoagulant therapy].

PMID- 15991615
TI  - [d-dimers: clinical interest].

PMID- 15991614
TI  - [Superficial thrombophlebitis].

PMID- 15991616
TI  - [Venous thromboembolism and digestive surgery].

PMID- 15991617
TI  - [Thromboembolism in orthopedics].

PMID- 15991618
TI  - [Venous thromboembolism and obstetric gynecology].

PMID- 15991619
TI  - [New anticoagulants: mechanism of action and therapeutic targets].

PMID- 15991620
TI  - [Venous thromboembolism and patient age].

PMID- 15991621
TI  - [Deep vein thrombosis of the upper limb with pulmonary embolism under short
      peripheral catheterization].

PMID- 15991622
TI  - [Fibrous mediastinitis secondary to a seminoma].

PMID- 15991623
TI  - [Can independent clinical research survive?].

PMID- 15991624
TI  - [Cancer screening: when and how?].
AB  - Advances in cancer biology have led to the development of screening tests that
      allow an early diagnosis. Cancer screening is not just the matter of a single
      individual patient, it is a matter of public health. Screening is commonly viewed
      as of no harm, when in fact harms are associated with the majority of cancer
      screening tests. A test should only be used when the potential of benefit clearly
      outweighs the risks for harm. The data in the literature are not always clear cut
      and in a lot of cases guidelines are somewhat controversial. What is known and
      what is unknown about screening tests is quite different from what is believed by
      the public. The aim of this work is to summarize the different methods and
      guidelines in cancer screening to help choosing the right test at the right time
      for the right person.

PMID- 15991625
TI  - [PET contribution in oncology].
AB  - Initial workup in oncology relies on histology and extensive staging of disease.
      Assessment of treatment response is also of paramount importance. Functional
      imaging with PET provides substantially more information than conventional
      radiology based on anatomic structures. PET applications in oncology are rapidly
      growing. We review herein the established and investigational indications for PET
      imaging, and also highlight some of its limitations.

PMID- 15991626
TI  - [Present chemoprevention and future vision].
AB  - Cancer chemoprevention is defined as the use of natural or synthetic agents to
      reverse, suppress or prevent carcinogenic progression to invasive cancer. The
      success of several clinical trials within high-risk patients suggests that
      chemoprevention is a rational and promising strategy. This review will resume the
      principal molecular mechanisms of chemoprevention and discuss results and
      clinical outcome of selected clinical trials. The difficulties in clinical
      application and future directions will be highlighted.

PMID- 15991627
TI  - [Breaking bad news].
AB  - Breaking bad news is one of the most stressful duties of the physician in
      oncology. Among other issues, it includes discussion of cancer diagnosis or the
      failure of therapy. The oncologist is often puzzled by an apprehension regarding
      the delivery of bad news. The fear to be exposed to unexpected strong emotional
      reactions by the patient, such as aggression or despair, may cause the oncologist
      to adopt unproductive coping strategies such as discussion about technical
      details while avoiding to deliver the main message. However, good communication
      skills are the key for a satisfying conversation with the patient. The
      oncologists' discomfort induced by the above mentioned apprehension is one of the
      most important barriers for a successful conversation.

PMID- 15991628
TI  - [Dangerous liaisons: relation between oncologist and general practitioner].
AB  - Due to the nature of the disease, patients often have a privileged and close
      relationship with their oncologist, and the oncologist also with their patients.
      This may in turn be detrimental to the relation between the general practitioner
      and the patient. Patients will not return to their general practitioner until end
      of life care or a consultation at the patient's home if necessary. In order to
      maintain a balance between the caretakers and assure appropriate involvement of
      the family physician, continuous communication and exchange of information are
      essential. This review identifies some of the problems and potential conflicts,
      which may arise, and discusses how the interaction could be improved.

PMID- 15991629
TI  - [New systemic therapies in oncology].
AB  - These last decades showed important progress in cancer systemic therapies. A
      better understanding of the differences between cancer cells and normal cells
      lead to the emergence of targeted therapies. These treatments interfere with
      different specific molecules playing a critical role in tumour growth or
      progression. On the other side, thanks to the development of new therapeutic
      substances, new modes of administration and to the improvement of supportive
      care, conventional chemotherapy is more effective and less toxic. The following
      review summarizes current progress with clinical impact observed these last
      years.

PMID- 15991630
TI  - [Plea for the family history...in the area of molecular oncology].
AB  - Oncological family history allows to estimate an empirical risk to develop
      malignant tumors. Nowadays family history is crucial to determine the indication
      to perform screening of cancer predisposing genes. Five to 10% of all cancers are
      the result of highly penetrant genes. Most of the genes responsible for familial
      cancer syndromes have been characterized. It is now feasible, by a simple blood
      sample, to detect germ-line alterations of these genes and to identify the at
      risk individuals. Specific screening and preventive strategies are recommended in
      the management of these high risk individuals.

PMID- 15991631
TI  - [Equality: the return?].

PMID- 15991632
TI  - [Echo of the 2005 ACC* (2). The war of stents has started].

PMID- 15991633
TI  - [Breast cancer: the Herceptin breakthrough].

PMID- 15991634
TI  - [Cloning horses and the merchants of the genetic temple].

PMID- 15991635
TI  - [A witch hunt evaluating the prevalence of hyperactivity in Switzerland].

PMID- 15991637
TI  - [A comprehensive hospitalization unit for prisoners].

PMID- 15991638
TI  - [Asthma in children].

PMID- 15991639
TI  - [Asthma school nurse. Interview by Marie-France Guerel].

PMID- 15991640
TI  - [Epidemiology of food allergies].

PMID- 15991641
TI  - [Intestinal flora and immunity in the adult human].

PMID- 15991642
TI  - [Nursing transfer form for the emergency ambulance service and pediatric
      intensive care unit of the Robert-Debre hospital].

PMID- 15991643
TI  - [Pulmonary embolism].

PMID- 15991644
TI  - [Efavirenz].

PMID- 15991645
TI  - [Zoonoses in France].

PMID- 15991646
TI  - ["Medicalizing the addiction field to make peace" Interview by Helen Delmotte and
      Marie-France Guerel].

PMID- 15991647
TI  - Attitudes about sex and marital sexual behavior in Hai Duong Province, Vietnam.
AB  - This study examines attitudes concerning sexual relations outside marriage and
      levels of marital sexual activity using data from married individuals from Hai
      Duong Province collected in 2001. Among individuals who live in urban areas, have
      more schooling, and were married after the late 1980s, acceptance is growing
      concerning intimate behavior without marital commitment and having sex with a
      future spouse. Schooling, urban residence, and recent marriage have stronger
      associations with less conservative attitudes among men than among women. Even
      among younger and better-educated respondents, acceptance of premarital and
      extramarital sex generally remains below a majority. The reported level of
      premarital sex is higher among men than among women, and lower than available
      estimates from other parts of Asia and the developing world. The reported level
      of sexual activity within marriage in Hai Duong Province is similar to that
      observed elsewhere, including Thailand and the United States. The incidence of
      sexual activity declines with age, and at all ages men are more likely than women
      to report having sex with their spouse. The implications of these gender
      differences in sexual attitudes and behavior are considered.

PMID- 15991648
TI  - Does Audio-CASI improve reports of risky behavior? Evidence from a randomized
      field trial among young urban men in India.
AB  - This study compares the effectiveness of audio computer-assisted self
      interviewing (Audio-CASI) with face-to-face interviews and self-administered
      questionnaires in collecting sensitive information on risky sexual and other
      behaviors among young men in urban India. A randomized study design compared data
      collected from 900 male college students using the three data-collection
      approaches and from 600 young men residing in slums using Audio-CASI and face-to
      face interviews. Among the college students, the reported prevalence of risky
      behaviors was generally higher for young men interviewed through the Audio-CASI
      approach than with face-to-face interviews; self-administered questionnaires
      failed to yield significantly higher estimates than face-to-face interviews.
      Among the slum residents, the results were more mixed; the Audio-CASI approach
      failed to yield consistently higher responses for many risky behaviors compared
      with the face-to-face interview mode. The results demonstrate that although Audio
      CASI appears to yield higher estimates of risky behavior among college-educated,
      computer-literate populations of young men, the efficacy of this approach among
      less-educated and less computer-literate populations appears more doubtful.

PMID- 15991650
TI  - The changing discourse on population and development: toward a new political
      demography.

PMID- 15991649
TI  - Providers' compliance with the balanced counseling strategy in Guatemala.
AB  - The balanced counseling strategy developed in Peru improved family planning care
      and clients' knowledge of their contraceptive method choice, but few providers
      adopted it. To expand its use, an algorithm was introduced and training, job
      aids, and reinforcement were supplied to Ministry of Health providers, most of
      whom were paraprofessionals, from two areas (40 clinics) in Guatemala. Mystery
      clients made pretest and post-test visits to these clinics and to providers from
      a nonequivalent control group (40 clinics). The results showed that the strategy
      was used in 85 percent of the controlled consultations at the experimental
      clinics. Use of the strategy improved quality of care regardless of the
      provider's performance at baseline and regardless of ethnic or regional
      differences. Counseling session length increased by nine minutes, but real-client
      load did not change. Guatemalan clients can be expected to benefit from the
      strategy. The increased session length has not yet caused problems, but it may
      pose policy dilemmas in the future.

PMID- 15991651
TI  - The Millennium Development Goals minus reproductive health: an unfortunate, but
      not disastrous, omission.

PMID- 15991652
TI  - The reproductive health community: a valuable asset for achieving the MDGs.

PMID- 15991653
TI  - Reproductive health and the MDGs: is the glass half full or half empty?

PMID- 15991654
TI  - Keeping sexual and reproductive health at the forefront of global efforts to
      reduce poverty.

PMID- 15991655
TI  - Excerpts from UN Millennium Project Reports.

PMID- 15991656
TI  - Ghana 2003: results from the Demographic and Health Survey.

PMID- 15991657
TI  - Kenya 2003: results from the Demographic and Health Survey.

PMID- 15991658
TI  - Pediatric oncology nursing research in the Children's Oncology Group: the second
      generation.

PMID- 15991659
TI  - Creating a novel structure for nursing research in a cooperative clinical trials
      group: the Children's Oncology Group experience.
AB  - OBJECTIVE: To describe a novel structure designed to integrate nursing research
      into the Children's Oncology Group (COG). DATA SOURCES: Review articles, reports,
      and newsleters. CONCLUSION: A new structure using nurse researcher-advanced
      practice nurse dyads has succesfully integrated nurse researchers into COG
      scientific activity, as evidenced by the development of concept proposals,
      companion protocols, nursing objectives in therapeutic trials, and nurse-led
      publications. IMPLICATIONS FOR NURSING PRACTICE: This provides a promising method
      for integrating nurse researchers and increasing multidisciplinary research
      collaboration in cooperative oncology group.

PMID- 15991660
TI  - Parental treatment decision making in pediatric oncology.
AB  - OBJECTIVE: To review progress and future plans for a research program about
      parents' making treatment decisions for their children with cancer. DATA SOURCES:
      Theoretical papers, review articles, and research reports. CONCLUSION: Three
      important questions need to be addressed to achieve the goal of supporting
      parents in treatment decision making: 1) Whatfactors predict a parent's preferred
      role iln decision making? 2) What are the critical outcomes from parental
      decision making that nurses could help to improve? 3) Is it role choice, actual
      role assumed, or congruence between preferred and actual role in decision making
      that predicts decision outcomes for the parents? IMPLICATIONS FOR NURSING
      PRACTICE: Research-based responses to the remaining questions about parent
      treatment decision making will help nurses develop and test interventions
      designed to support parents in their decision making experiences.

PMID- 15991661
TI  - Complementary and alternative medicine in pediatric oncology.
AB  - OBJECTIVES: To summarize research in complementary and alternative medicine (CAM)
      therapies used for children with cancer and to explore issues and directions for
      measuring outcomes of CAM therapies in children. DATA SOURCES: Scientific and
      research articles, internet for active research studies. CONCLUSION: CAM is
      increasingly used as adjunctive cancer therapies in pediatrics. Mind-body and
      touch therapies have the greatest evidencefor effectiveness in reducing
      psychological and physical stressors. Supplements and herbal therapies receive
      the greatest interest, however, and more research is needed to determine efficacy
      in improving symptoms or outcomes in children with cancer. IMPLICATIONS FOR
      NURSING PRACTICE: Mind-body and touch therapies can be used by nurses to reduce
      symptoms and anxiety in children. Potential risks and benefits should be
      determined for therapies that have no evidence.

PMID- 15991662
TI  - Collaborative clinical research on end-of-life care in pediatric oncology.
AB  - OBJECTIVES: To present an overview of research into end-of-life (EoL) care for
      pediatric patients with cancer and to describe research completed by a newly
      formed collaboration of researchers. DATA SOURCES: Professional group position
      papers and guidelines; research studies. CONCLUSION: Studies to date in pediatric
      EoL care used retrospective, descriptive, or pilot intervention designs, have
      been conducted in single-institution settings, and have included small numbers of
      patients. Most studies have explored perspectives of parents and health care
      professionals but have omitted the perspective of the dying child. IMPLICATIONS
      FOR NURSING PRACTICE: Advancing the science of EoL care will depend on
      intervention-based clinical trials that include the perspective of the dying
      child in addi tion to parents and health care professionals.

PMID- 15991663
TI  - Comparing research priorities for pediatric oncology from two panels of experts.

PMID- 15991664
TI  - Modeling mercury fluxes and concentrations in a Georgia watershed receiving
      atmospheric deposition load from direct and indirect sources.
AB  - This paper presents a modeling analysis of airborne mercury (Hg) deposited on the
      Ochlockonee River watershed located in Georgia. Atmospheric deposition monitoring
      and source attribution data were used along with simulation models to calculate
      Hg buildup in the subwatershed soils, its subsequent runoff loading and delivery
      through the tributaries, and its ultimate fate in the mainstem river. The
      terrestrial model calculated annual watershed yields for total Hg ranging from
      0.7 to 1.1 microg/m2. Results suggest that approximately two-thirds of the
      atmospherically deposited Hg to the watershed is returned to the atmosphere, 10%
      is delivered to the river, and the rest is retained in the watershed. A check of
      the aquatic model results against survey data showed a reasonable agreement.
      Comparing observed and simulated total and methylmercury concentrations gave root
      mean square error values of 0.26 and 0.10 ng/L, respectively, in the water
      column, and 5.9 and 1 ng/g, respectively, in the upper sediment layer.
      Sensitivity analysis results imply that mercury in the Ochlockonee River is
      dominated by watershed runoff inputs and not by direct atmospheric deposition,
      and that methylmercury concentrations in the river are determined mainly by net
      methylation rates in the watershed, presumably in wetted soils and in the
      wetlands feeding the river.

PMID- 15991665
TI  - The Steubenville Comprehensive Air Monitoring Program (SCAMP): analysis of short
      term and episodic variations in PM2.5 concentrations using hourly air monitoring
      data.
AB  - One-hour average ambient concentrations of particulate matter (PM) with an
      aerodynamic diameter < 2.5 microm (PM2.5) were determined in Steubenville, OH,
      between June 2000 and May 2002 with a tapered element oscillating microbalance
      (TEOM). Hourly average gaseous copollutant [carbon monoxide (CO), sulfur dioxide
      (SO2), nitrogen oxide (NOx), and ozone (O3)] concentrations and meteorological
      conditions also were measured. Although 75% of the 14,682 hourly PM2.5
      concentrations measured during this period were < or = 17 microg/m3,
      concentrations > 65 microg/m3 were observed 76 times. On average, PM2.5
      concentrations at Steubenville exhibited a diurnal pattern of higher early
      morning concentrations and lower afternoon concentrations, similar to the diurnal
      profiles of CO and NO(x). This pattern was highly variable; however, PM2.5
      concentrations > 65 microg/m3 were never observed during the mid-afternoon
      between 1:00 p.m. and 5:00 p.m. EST. Twenty-two episodes centered on one or more
      of these elevated concentrations were identified. Five episodes occurred during
      the months June through August; the maximum PM2.5 concentration during these
      episodes was 76.6 microg/m3. Episodes occurring during climatologically cooler
      months often featured higher peak concentrations (five had maximum concentrations
      between 95.0 and 139.6 microg/m3), and many exhibited strong covariation between
      PM2.5 and CO, NO(x), or SO2. Case studies suggested that nocturnal surface-based
      temperature inversions were influential in driving high nighttime concentrations
      of these species during several cool season episodes, which typically had
      dramatically lower afternoon concentrations. These findings provide insights that
      may be useful in the development of PM2.5 reduction strategies for Steubenville,
      and suggest that studies assessing possible health effects of PM2.5 should
      carefully consider exposure issues related to the intraday timing of PM2.5
      episodes, as well as the potential for toxicological interactions among PM2.5,
      and primary gaseous pollutants.

PMID- 15991666
TI  - Management and performance of Taiwan's waste recycling fund.
AB  - Taiwan's resource recycling program was formally established in 1989, starting
      with the mandatory recycling of polyethylene terephthalate bottles. The number of
      mandatory regulated materials was extended to 8 categories with 27 items by 2002.
      Because of false data reporting, financial scandal, lack of transparency of the
      system, and the demand from parliament, the recycling policy has gradually
      changed from entirely privatized to being nationalized. Currently, the structure
      is built on six main bodies: fund management committee, consumers, industries
      responsible, recyclers, fee reviewing committee, and auditing agents. The
      industries that are responsible submit a fee, which is set by the fee reviewing
      committee, to the waste recycling fund (WRF), which is operated by the fund
      management committee. The auditing agents routinely check the responsible
      industries by documentation review as well as on-site counting to ensure that the
      fee is correctly submitted. The WRF provides initiatives to collect and dispose
      of the end-of-life products. The fund is split into a trust fund and a
      nonbusiness fund to deal with the collection, disposal, and treatment of the
      listed materials. The latter deals with the supporting works and ensures that the
      system runs effectively. The ratio of trust fund to nonbusiness fund is 80-20%.
      It is no doubt that the current practice achieves some improvements. Household
      waste has been reduced by 22%. And, most importantly, the benefit-to-cost ratio
      was as high as 1.24. However, similar to other state-owned systems, the resource
      recycling program has been criticized for false reporting from the responsible
      industries, a rigid system, and complicated procedures. To build a sustainable
      enterprise, the recycling program should be privatized as the recycling market
      and operating procedures are well established and fully mature.

PMID- 15991667
TI  - Real-time measurements of jet aircraft engine exhaust.
AB  - Particulate-phase exhaust properties from two different types of ground-based jet
      aircraft engines--high-thrust and turboshaft--were studied with real-time
      instruments on a portable pallet and additional time-integrated sampling devices.
      The real-time instruments successfully characterized rapidly changing particulate
      mass, light absorption, and polycyclic aromatic hydrocarbon (PAH) content. The
      integrated measurements included particulate-size distributions, PAH, and carbon
      concentrations for an entire test run (i.e., "run-integrated" measurements). In
      all cases, the particle-size distributions showed single modes peaking at 20-40nm
      diameter. Measurements of exhaust from high-thrust F404 engines showed relatively
      low-light absorption compared with exhaust from a turboshaft engine. Particulate
      phase PAH measurements generally varied in phase with both net particulate mass
      and with light-absorbing particulate concentrations. Unexplained response
      behavior sometimes occurred with the real-time PAH analyzer, although on average
      the real-time and integrated PAH methods agreed within the same order of
      magnitude found in earlier investigations.

PMID- 15991668
TI  - Electrostatic enhancement of collection efficiency of the fibrous filter
      pretreated with ionic surfactants.
AB  - A study of the electrostatic enhancement of collection efficiency of filters
      pretreated with ionic surfactants has been carried out in controlled conditions
      with monodisperse aerosols. Cationic surfactant (dimethyl dioctadecylammonium
      bromide [DDAB]) and anionic surfactant (sodium oleate [SO]) were used to pretreat
      polypropylene fibrous filters as the positively and negatively charged filters,
      respectively. The effects of aerosol size, aerosol charge state, face velocity,
      aerosol type, and relative humidity (RH) were considered to elucidate their
      influence on the aerosol penetration. Results indicate that penetration through
      surfactant-pretreated filters was lower than that through untreated filters, and
      pretreatment of the filter with surfactant was observed not to affect the
      structure of the filter. The electrofieldmeter direct-measured the very clear
      electric field of filter when treating ionic surfactants. The results proved that
      pretreatment with surfactant caused filters to become charged. Comparing
      penetration through surfactant-pretreated filters with that through untreated
      filters with neutral aerosol, the penetration reduction factor of the surfactant
      pretreated filters was in the range 1.3-2.2. Comparing aerosol penetration
      through the surfactant-pretreated filters with singly charged aerosol with that
      through untreated filters with uncharged aerosol indicates that the former
      decreases by a factor of 1.8-48.8. The surface fiber charges of the DDAB- and SO
      pretreated filters were calculated to be 2.02 x 1(-10) C/m and -1.53 x 10(-1)
      degrees C/m. Moreover, the aerosol penetrations through the surfactant-pretreated
      filters increased with the face velocity. Surfactant-pretreated filters performed
      better against solid aerosol than against liquid aerosol. RH has no effect on
      aerosol penetration through the surfactant-pretreated filters. Regression
      equations for Coulombic and dielectrophoretic single-fiber efficiencies in terms
      of the dimensionless parameters could be fitted by the experimental measurements
      of surfactant-pretreated filters in this work.

PMID- 15991669
TI  - Bio-oxidation of airborne volatile organic compounds in an activated sludge
      aeration tank.
AB  - An activated sludge aeration tank (40 x 40 x 300 cm, width x length x height)
      with a set of 2-mm orifice air spargers was used to treat gas-borne volatile
      organic compounds (VOCs; toluene, p-xylene, and dichloromethane) in air streams.
      The effects of liquid depth (Z), aeration intensity (G/A), the overall mass
      transfer rate of oxygen in clean water (KLaO2), the Henry's law constant of the
      tested VOC (H), and the influent gaseous VOC concentration (C0) on the efficiency
      of removal of VOCs were examined and compared with a literature-cited model.
      Results show that the measured VOC removal efficiencies and those predicted by
      the model were comparable at a G/A of 3.75-11.25 m3/m2 hr and C0 of approximately
      1000-6000 mg/m3. Experimental data also indicated that the designed gas treatment
      reactor with KLaO2 = 5-15 hr(-l) could achieve > 85% removal of VOCs with H =
      0.24-0.25 at an aerated liquid depth of 1 m and > 95% removal of dichloromethane
      with H = 0.13 at a 1-m liquid depth.

PMID- 15991670
TI  - Bioaerosol generation at large-scale green waste composting plants.
AB  - Bioaerosol release from composting plants is a cause of concern because of the
      potential health impacts on site workers and local residents. A one-year
      monitoring was undertaken in a typical composting plant treating green wastes by
      windrowing in the open. Aspergillus fumigatus spores and mesophilic bacteria were
      used as monitoring parameters and were collected in a six-stage Andersen sampler
      impactor from the air at different locations and during different operational
      activities. Background concentrations of both microorganisms were generally below
      1000 colony-forming units m(-3) when no vigorous activity was taking place.
      Shredding of fresh green wastes, pile turning, and screening of mature compost
      were identified as the activities generating the highest amounts of both
      bioaerosols 40 m downwind of the composting pad. These air concentrations were
      approximately 2 log units higher than background levels. Screening of mature
      compost generated lower amounts of A. fumigatus than the other two activities (an
      average of 1 log unit higher than background levels). Workers were identified as
      the main potential receptors of high bioaerosol concentrations in areas close to
      the composting pad, whereas no major risk for local residents was expected
      because the concentrations recorded at distances of 200 and 300 m downwind of the
      operational area were not significantly different from background levels.

PMID- 15991671
TI  - Investigation of nitrogen-bearing species in catalytic steam gasification of
      poultry litter.
AB  - The production of broiler chickens has become one of the largest sectors in U.S.
      agriculture, and the growing demand for poultry has led to an annual production
      growth rate of 5%. With increased demand for poultry, litter management has
      become a major challenge in the agriculture industry. Although the catalytic
      steam gasification has been accepted as a possible and feasible method for litter
      management, concern has been expressed about the presence of nitrogen and
      phosphorus containing species in the fuel gas and/or in the final solid residue.
      The possible release of phosphorus as phosphine gas in the fuel gas can have an
      adverse impact on the environment. Similarly, possible release of ammonia from
      the nitrogen containing species is also not acceptable. Hence, under partial U.S.
      Department of Agriculture support, a study was conducted to examine the fate and
      the environmental impact of the nitrogen- and phosphorus-containing species
      released during catalytic steam gasification of poultry litter. From various
      preliminary tests, it was concluded that most (approximately 100%) of the
      phosphorus would remain in the residue, and some (20-70%) of the nitrogen would
      end up as ammonia in the fuel gas. The effects of temperature, catalyst loading,
      and type of catalyst on ammonia liberation were studied in a muffled furnace
      setup at atmospheric pressure. The fraction of nitrogen released as ammonia was
      found to decrease with an increase in temperature during pyrolysis and steam
      gasification. It also decreased with an increase in catalyst loading.

PMID- 15991672
TI  - Summer and winter nonmethane hydrocarbon emissions from on-road motor vehicles in
      the Midwestern United States.
AB  - On-road vehicle emission rates of nonmethane hydrocarbons (NMHCs) were measured
      in two tunnels in Milwaukee, WI, in summer 2000 and winter 2001. Seasonal ambient
      temperatures in the Midwestern United States vary more widely than in locations
      where most studies of NMHC emissions from vehicle fleets have been conducted.
      Ethanol is the added fuel oxygenate in the area, and, thus, emissions measured
      here are of interest as other regions phase out methyl tertiary butyl ether and
      increase the use of ethanol. Total emissions of NMHCs in three types of tunnel
      tests averaged 4560 +/- 800 mg L(-1) fuel burned (average +/- standard error). To
      investigate the impact of cold start on vehicle emissions, samples were collected
      as vehicles exited a parking structure in subzero temperatures. NMHC emissions in
      the subzero cold-start test were 8830 +/- 190 mg L(-1) fuel-nearly double the
      tunnel emissions. Comparison of ambient data for the Milwaukee area with tunnel
      emissions showed the impact of seasonal differences in fuels and emissions on the
      urban atmosphere. Composition of fuel samples collected from area gas stations in
      both seasons was correlated with vehicle emissions; the predominant difference
      was increased winter emissions of lighter hydrocarbons present in winter
      gasoline. A chemical mass balance model was used to determine the contributions
      of whole gasoline and gasoline headspace vapors to vehicle emissions in the
      tunnel and cold-start tests, which were found to vary with season. Results of the
      mass balance model also indicate that partially combusted components of gasoline
      are a major contributor to emissions of aromatic compounds and air toxic
      compounds, including benzene, toluene, xylenes, napthalene, and 1,3-butadiene,
      whereas air toxics hexane and 2,2,4-trimethylpentane are largely attributed to
      gasoline and headspace vapors.

PMID- 15991673
TI  - Field enhancements of packed-bed performance for low-concentration acidic and
      basic-waste gases from semiconductor manufacturing process.
AB  - Low-concentration acidic and basic-waste gas pollutants contribute significantly
      in the total emission of a facility. Previous results show that the control of
      high volumetric flow rate (approximately 500 m3/min), low-concentration acidic (<
      1 ppm by vol) and basic (< 3 ppm by vol) gases from semiconductor process vent,
      by conventional wet scrubbing technique is a challenging task. This work was
      targeted to enhance the performance of packed beds for high-volumetric flow rate,
      low-concentration acidic (HF, HCl), and basic (NH3)-waste gases from the
      semiconductor manufacturing process. The methodology used to meet the goal was
      the application of fine-water mist over the inlet stream before entering to the
      packed bed and use of the surfactant with mist/packed-bed liquid in low
      concentration. An experimental study was carried out in two acid-packed beds to
      optimize the operating conditions, such as pH of the liquid, circulating liquid
      flow rate, blow-down cycle, and so forth. The relationship among liquid pH,
      liquid ionic concentration, and the removal efficiency of the packed bed for the
      pollutants has been discussed considering chemical equilibrium, two-film theory,
      and Henry's law. For the potential utilization of scrubbing water, the dependency
      of the efficiency on blow-down cycle was studied, and a mechanism is suggested.
      The proposed water-mist surfactant system was installed in two acid-packed beds,
      and performance of the packed beds was compared. The background efficiencies of
      the acid-packed beds for HF, HCl, and NH3 were found max to be (n = 11) 53, 40,
      and 27%, whereas after installation of the system, they increased significantly
      and became 76 +/- 13% (n = 10), 76 +/- 8% (n = 7), and 78 +/- 7% (n = 7),
      respectively, for inlet concentrations of HF and HCl < 1 ppm and NH3 < 14 ppm.
      The mechanism by which the surfactants operate to enhance the removal in
      scrubbing process is suggested considering the hydrodynamic effect and the
      interfacial effect with the charge-generating characteristic of surfactants on
      water surface, when dissolved into water. The results show that a proposed
      rectification system can effectively reduce the emission rates below the
      regulatory level (0.6 kg/hr) at the present conditions of the facility.

PMID- 15991674
TI  - Open-path tunable diode laser absorption spectroscopy for acquisition of fugitive
      emission flux data.
AB  - Air pollutant emission from unconfined sources is an increasingly important
      environmental issue. The U.S. Environmental Protection Agency (EPA) has developed
      a ground-based optical remote-sensing method that enables direct measurement of
      fugitive emission flux from large area sources. Open-path Fourier transform
      infrared spectroscopy (OP-FTIR) has been the primary technique for acquisition of
      pollutant concentration data used in this emission measurement method. For a
      number of environmentally important compounds, such as ammonia and methane, open
      path tunable diode laser absorption spectroscopy (OP-TDLAS) is shown to be a
      viable alternative to Fourier transform spectroscopy for pollutant concentration
      measurements. Near-IR diode laser spectroscopy systems offer significant
      operational and cost advantages over Fourier transform instruments enabling more
      efficient implementation of the measurement strategy. This article reviews the
      EPA's fugitive emission measurement method and describes its multipath tunable
      diode laser instrument. Validation testing of the system is discussed. OP-TDLAS
      versus OP-FTIR correlation testing results for ammonia (R2 = 0.980) and methane
      (R2 = 0.991) are reported. Two example applications of tunable diode laser-based
      fugitive emission measurements are presented.

PMID- 15991675
TI  - Plume rise in a shear layer with neutral stability.
AB  - Several solutions have been published to predict the rise of buoyant plumes in a
      shear layer with a power-law velocity profile. Each of these solutions is either
      a special case or is based on oversimplifying assumptions. In this paper,
      solutions to the plume-rise equations are given for buoyant and nonbuoyant plumes
      with initial vertical momentum. Solutions are given for both point sources and
      sources with a finite initial size under neutral stability. For a constant wind
      speed, these solutions simplify to the conventional plume-rise equations.

PMID- 15991676
TI  - Development of a United States-Mexico Emissions Inventory for the Big Bend
      Regional Aerosol and Visibility Observational (BRAVO) Study.
AB  - The Big Bend Regional Aerosol and Visibility Observational (BRAVO) Study was
      commissioned to investigate the sources of haze at Big Bend National Park in
      southwest Texas. The modeling domain of the BRAVO Study includes most of the
      continental United States and Mexico. The BRAVO emissions inventory was
      constructed from the 1999 National Emission Inventory for the United States,
      modified to include finer-resolution data for Texas and 13 U.S. states in close
      proximity. The first regional-scale Mexican emissions inventory designed for air
      quality modeling applications was developed for 10 northern Mexican states, the
      Tula Industrial Park in the state of Hidalgo, and the Popocatepetl volcano in the
      state of Puebla. Emissions data were compiled from numerous sources, including
      the U.S. Environmental Protection Agency (EPA), the Texas Natural Resources
      Conservation Commission (now Texas Commission on Environmental Quality), the
      Eastern Research Group, the Minerals Management Service, the Instituto Nacional
      de Ecologia, and the Instituto Nacional de Estadistica Geografia y Informatica.
      The inventory includes emissions for CO, nitrogen oxides, sulfur dioxide,
      volatile organic compounds (VOCs), ammonia, particulate matter (PM) < 10 microm
      in aerodynamic diameter, and PM < 2.5 microm in aerodynamic diameter. Wind-blown
      dust and biomass burning were not included in the inventory, although high
      concentrations of dust and organic PM attributed to biomass burning have been
      observed at Big Bend National Park. The SMOKE modeling system was used to
      generate gridded emissions fields for use with the Regional Modeling System for
      Aerosols and Deposition (REMSAD) and the Community Multiscale Air Quality model
      modified with the Model of Aerosol Dynamics, Reaction, Ionization and Dissolution
      (CMAQ-MADRID). The compilation of the inventory, supporting model input data, and
      issues encountered during the development of the inventory are documented. A
      comparison of the BRAVO emissions inventory for Mexico with other emerging
      Mexican emission inventories illustrates their uncertainty.

PMID- 15991677
TI  - [New therapies for non-small cell lung cancer].
AB  - Lung cancer is one of the most frequent causes of death from cancer. Non-small
      cell lung cancer represents approximately 80% of the total pulmonary
      malignancies. Unfortunately, most non-small cell lung cancer patients present
      advanced disease at diagnosis and a very poor prognosis. Despite advances in our
      understanding of the molecular and genetic basis of non-small cell lung cancer,
      and improvement in therapy with surgery, conventional chemotherapy, and
      radiation, 5-year survival for patients with this diagnosis remains poor and the
      disease remains a clinical challenge. However, strategies of molecular based
      therapies are in development and it is hoped that these new approaches will
      continue to improve survival for patients with advanced lung cancer. Any
      categorization of these drugs is hard, with overlap in several features. The main
      investigated agents are epidermal growth factor receptor (EGFR) family
      inhibitors, angiogenesis inhibitors and antivascular drugs, signal transduction
      inhibitors, apoptosis inducers, eicosanoid pathway inhibitors and
      immunotherapeutic drugs. To date, few of these new drugs can offer trust of a
      substantial influence on the natural history of non-small cell lung cancer, and
      disappointing results are more commonly reported than encouraging ones.
      Nevertheless, tailored treatment for non-small cell lung cancer patients may
      represent a further chance of tumor control and symptom palliation. This review
      presents an overview of molecular targeted therapy in non-small cell lung cancer.

PMID- 15991679
TI  - [Treatment experience with metformin in polycystic ovary syndrome].
AB  - Based on the favourable international experience with metformin in the most
      common female endocrine disease, the polycystic ovary syndrome, which has insulin
      resistance in the background, the author's treatment advice has been this in such
      cases since early 2002: for sexually active women who do not want to become
      pregnant for the time being, anti-androgenic contraceptive pill; for those who do
      not want to take contraceptives, contraceptives are contraindicated, or who do
      want to conceive, metformin. 44/71 non-diabetic patients opted for metformin
      treatment. A 3 to 30 month follow-up period of 25 patients could be evaluated.
      Seven patients had transient vertigo, diarrhoea or abdominal discomfort at the
      beginning of the treatment. The severity of acne of 21 patients diminished
      significantly by three months and the acne score fell close to the half value by
      six months. Body hair of 17 women with hypertrichosis diminished significantly by
      six months. Menstrual cycles of 8/13 patients became regular by three months; a
      further woman became pregnant and continued metformin throughout pregnancy. Her
      blood pressure remained normal despite suffering from pre-eclampsia during all of
      her previous pregnancies. The average body mass index and waist-to-hip ratio did
      not change significantly during the follow-up. Apart from few initial, transient
      side effects, disadvantages of the treatment were not found. Long-term metformin
      treatment resulted in significant improvement of the symptoms of patients with
      polycystic ovary syndrome.

PMID- 15991678
TI  - [Pharmacogenetics of inflammatory bowel disease].
AB  - There are interindividual variations with regard to efficacy and toxicity of many
      commonly employed drugs. Major causes of interindividual differences of drug
      effects include genetic variations of drug-metabolizing enzymes, transporters and
      targets. Pharmacogenetics studies the genetic background of the interindividual
      variations of drug response. By means of preliminary genetic screening
      personalized treatment can be achieved, drugs with low efficacy and many side
      effects can be avoided. The pharmacogenetically best studied medications of
      inflammatory bowel disease are azathioprine/6-mercaptopurine. It is obvious that
      there is a genetic background of the efficacy and toxicity of corticosteroids, 5
      ASA drugs, infliximab and other immunosuppressors as well, but further studies
      now require to confirm the functional significance of it. Therefore, at present,
      the application and clinical usefulness of pharmacogenetics in the management of
      inflammatory bowel disease is limited. The aims of future investigations are
      understanding of the mechanism of drug action, identification of new drug targets
      and acquainting with genetic factors that determine drug response.

PMID- 15991680
TI  - [Optical biopsy of the retina in vivo: on optical coherence tomography and its
      clinical use in ophthalmology].
AB  - Optical Coherence Tomography (OCT) is a novel, non invasive imaging method, which
      enables in vivo assessment of living tissues, providing near histological
      resolution images. The first description of its clinical introduction was in
      ophthalmology, which substantially changed our view of specific retinal diseases.
      OCT technology is slowly penetrating into other medical fields, supposedly
      opening new perspectives with the possibility of in vivo optical biopsy. The aim
      of this paper is to review the clinical use of OCT, with special emphasis on
      ophthalmology.

PMID- 15991681
TI  - [Intracardiac echocardiography in clinical cardiac electrophysiology: review and
      first Hungarian experience].
AB  - During the last two decades revolutionary diagnostic and therapeutic changes were
      implemented in the management of patients with arrhythmias. Since the arrhythmia
      substrate is frequently associated with certain anatomical structures or
      morphological variants, improved imaging has increasing role in the improvement
      of these treatments. Furthermore, novel catheter ablation approaches require
      catheter placement to sites, which may be associated with increased complication
      risk. Therefore imaging has a crucial role both in guiding and improving safety
      of electrophysiology procedures. Recently, intracardiac echocardiography became
      available providing excellent accuracy in direct visualization of anatomical
      landmarks. Intracardiac echocardiography is therefore a potentially useful tool
      for guiding electrophysiology procedures. The first two Hungarian cases with
      intracardiac echocardiography are presented with a broad background in this
      comprehensive review.

PMID- 15991682
TI  - Water safety and disaster management procedures reported by Louisiana health care
      food service directors.
AB  - Eighty health care food service directors in Louisiana were surveyed regarding
      their knowledge of policies and procedures their facilities have for water
      management in natural disasters and emergencies. Questionnaires were mailed to
      hospital and long-term-care food service directors in Louisiana. Responses
      indicated that hurricanes were the most common natural disaster affecting the
      facilities, frequently resulting in loss of electrical-power and natural-gas
      services. Food service directors had some knowledge of the content of
      emergency/disaster plans in their facilities, but were unfamiliar with procedures
      for obtaining water from alternative sources. The majority of health care
      facilities did not test water quality as part of normal operating procedures. To
      facilitate production of safe, quality food from alternative potable-water
      sources when needed, health care food service directors should review the
      emergency/disaster plans of their facilities for potable-water procedures.

PMID- 15991683
TI  - Clearing the air: a model for investigating indoor air quality in Texas schools.
AB  - This pilot project focused on the assessment of indoor air quality at a local
      high school in Galveston, Texas, using methods based on guidelines for the U.S.
      Environmental Protection Agency's Indoor Air Quality Tools for Schools program.
      Tools for Schools, developed for evaluating and ensuring acceptable air quality
      for schools, takes a low-cost, minimal-involvement, primarily educational
      approach. The authors also compared the findings from this approach with the
      results of an air-sampling program. The overall goal was to determine if use of
      Tools for Schools was sufficient to identify conditions with the potential to
      cause adverse health effects. The primary objectives were to 1) establish an
      indoor air quality committee for the school to implement Tools for Schools
      assessments and management strategies, 2) collect air quality data in high-risk
      areas identified within the school by the indoor air quality committee, 3)
      collect outdoor air quality data at or in close proximity to the school, and 4)
      develop methods and instruments for assessing environmental risks associated with
      daily school attendance. Data were gathered on levels of formaldehyde and other
      volatile organic compounds (VOCs), ozone, particulate matter (PM10), mold,
      relative humidity, and temperature. Data values for each sampled pollutant were
      compared with federal standards, recommended values established by the American
      Conference of Governmental Industrial Hygienists for non-industrial populations,
      and effects screening levels developed by the Texas Commission on Environmental
      Quality. Levels of all VOCs except formaldehyde were found to be well within
      guidelines, as were ozone and particulate-matter levels. Mold, however, was
      widespread, including both common species and species associated with allergy and
      asthma, such as Aspergillus and Alternaria. In general, Tools for Schools
      provides an excellent foundation for a school indoor air quality program,
      although the authors did find it necessary to streamline data collection and did
      find that mold with the potential for adverse health effects was present, albeit
      not visible in some areas.

PMID- 15991684
TI  - Health professionals hold positive attitudes toward biotechnology and genetically
      engineered foods.
AB  - Few biotechnology processes have elicited the degree of controversy that genetic
      manipulation of food through recombinant DNA technology has. Research has shown
      that consumers turn to health professionals for answers to questions regarding
      health and nutrition. This study sought to assess the knowledge, attitudes, and
      beliefs of physicians (MDs/DOs), nurse practitioners (NPs), and registered
      dietitians (RDs) toward food biotechnology and genetic engineering (GE). Six
      hundred three-part, self-administered surveys were sent to health professionals
      holding active professional licenses. Statistical analysis included analysis of
      variance with Tukey's HSD and Scheffe's post hoc tests. Attitudes toward GE were
      positive. MDs held more positive attitudes than NPs or RDs (p = .000). MDs and
      NPs supported the use of GE to improve plant resistance to pests; RDs tended to
      support nutritional-improvement technology. All groups supported the use of GE to
      produce human medicines and the current Food and Drug Administration (FDA)
      labeling policy. No profession was more knowledgeable than another. Biotechnology
      holds the potential to positively affect human health. All health professionals
      can facilitate or diminish this process through their understanding of the
      technology and their ability to communicate effectively about the science and
      issues associated with biotechnology.

PMID- 15991685
TI  - Shirt designs for sun protection.
AB  - The objectives of the study reported here were to document consumer attitudes,
      risk understanding, and behaviors with respect to sun safety and to define
      consumer preferences for protective shirt design and labeling. A sample of 1,508
      adults was surveyed at the 2002 Farm Progress Show sun-safety exhibit. Results
      showed that people generally understood the longterm risk from exposure to
      ultraviolet radiation, but did not routinely use sun-protective clothing to avoid
      it. Design features preferred by consumers for sun-safe shirts were significantly
      related to demographic characteristics, including age, education, sex,
      occupation, and employment status. Overall, the sun-safe shirt design most
      preferred can be summarized as a casual-style, solid-color, knit shirt with a
      crew neck or collar. Over 80 percent of participants favored Ultraviolet
      Protective Factor labeling as well as other consumer labeling such as information
      on care, fiber content, colorfastness, and finishes applied to shirts. Industrial
      and educational implications are provided.

PMID- 15991686
TI  - Application of constructed wetlands to the treatment of leachates from a
      municipal solid waste landfill in Ibadan, Nigeria.
AB  - Leachates are wastewater generated principally from landfills and solid waste
      disposal sites. Leachates emanating from municipal wastes are a major source of
      surface and groundwater pollution worldwide. Globally, leachates have been
      implicated in low yield of farm produce, developmental anomalies, low birth
      weights, leukemia incidence, and other cancers in communities around the site.
      They have also been implicated in hazards to the environment, loss of
      biodiversity, and contamination of water sources. At Aba-Eku in Nigeria,
      leachates are being discharged into the Omi Stream without treatment. A study was
      conducted on a method of leachate treatment that passes the leachate through
      constructed wetlands using Ipomoea aquatica (Forsk), a locally available plant
      found close to the landfill site. The aim of the study was to evolve a
      sustainable and cost-effective method of treatment whose effluents can be
      discharged into the Omi Stream with no or minimal impact. The study was
      descriptive and analytical in design. Samples were collected and analyzed with
      standard methods for pH, suspended solids (SS), biochemical oxygen demand (BOD),
      chemical oxygen demand (COD), ammonia, nitrate, and trace metals. Raw leachates
      were turbid and amber in color and contained suspended solids (197.5 mg/L),
      ammonia (610.9 mg/L), lead (1.64 mg/L), iron (198.10 mg/L), and manganese (23.20
      mg/L). When the leachates were passed through the constructed wetland with eight
      hours' detention time, effluents showed significant reductions in suspended
      solids (81.01 percent), BOD (86.03 percent), and ammonia (97.77 percent). The
      study shows that a constructed wetland is a feasible tool for the treatment of
      leachates before their disposal into the environment in Nigeria and can help
      safeguard environmental quality.

PMID- 15991687
TI  - Children's environmental health--why the big deal?

PMID- 15991688
TI  - On one of the pleasures of working for NEHA.

PMID- 15991689
TI  - Accentuating the negative: Tom Wedgwood (1771-1805), photography and perception.

PMID- 15991690
TI  - Geometric and perceptual effects of the location of the observer vantage point
      for linear-perspective images.
AB  - New geometric analyses are presented of three impressive examples of the effects
      of location of the vantage point on virtual 3-D spaces conveyed by linear
      perspective images. In the 'egocentric-road' effect, the perceived direction of
      the depicted road is always pointed towards the observer, for any position of the
      vantage point. It is shown that perspective images of real-observer-aimed roads
      are characterised by a specific, simple pattern of projected side lines. Given
      that pattern, the position of the observer, and certain assumptions and
      perspective arguments, the perceived direction of the virtual road towards the
      observer can be predicted. In the 'skewed balcony' and the 'collapsing ceiling'
      effects, the position of the vantage point affects the impression of alignment of
      the virtual architecture conveyed by large-scale illusionistic paintings and the
      real architecture surrounding them. It is shown that the dislocation of the
      vantage point away from the viewing position prescribed by the perspective
      construction induces a mismatch between the painted vanishing point of elements
      in the picture and the real vanishing point of corresponding elements of the
      actual architecture. This mismatch of vanishing points provides visual
      information that the elements of the two architectures are not mutually parallel.

PMID- 15991691
TI  - Two reference frames for visual perception in two gravity conditions.
AB  - The processing and storage of visual information concerning the orientation of
      objects in space is carried out in anisotropic reference frames in which all
      orientations are not treated equally. The perceptual anisotropies, and the
      implicit reference frames that they define, are evidenced by the observation of
      'oblique effects' in which performance on a given perceptual task is better for
      horizontally and vertically oriented stimuli. The question remains how the
      preferred horizontal and vertical reference frames are defined. In these
      experiments cosmonaut subjects reproduced the remembered orientation of a visual
      stimulus in 1g (on the ground) and in 0g, both attached to a chair and while free
      floating within the International Space Station. Results show that while the
      remembered orientation of a visual stimulus may be stored in a multimodal
      reference frame that includes gravity, an egocentric reference is sufficient to
      elicit the oblique effect when all gravitational and haptic cues are absent.

PMID- 15991692
TI  - White's effect: removing the junctions but preserving the strength of the
      illusion.
AB  - White's effect (also known as the Munker White effect) is a lightness illusion in
      which, contrary to expectations based on simultaneous contrast and Wallach's
      rule, a gray rectangle predominantly surrounded by white appears lighter than an
      identical rectangle that is mainly surrounded by black. The illusion is often
      explained in terms of T-junctions that are formed by the three-way intersection
      of the gray rectangle, a black stripe, and a white stripe. I present a circular
      variant of White's effect in which all the junctions have been removed without
      significantly affecting the strength of the illusion, suggesting that junctions
      are not an important consideration in all versions of White's effect.

PMID- 15991693
TI  - Remote effects of highlights on gloss perception.
AB  - The perception of a glossy surface in a static monochromatic image can occur when
      a bright highlight is embedded in a compatible context of shading and a bounding
      contour. Some images naturally give rise to the impression that a surface has a
      uniform reflectance, characteristic of a shiny object, even though the highlight
      may only cover a small portion of the surface. Nonetheless, an observer's
      impression of gloss may be partial and nonuniform at image regions outside of a
      highlight. A rating scale and small probe points indicating image locations were
      used to investigate the differential perception of gloss within a single object.
      Gloss ratings given by observers were not uniform across a surface, but decreased
      as a function of distance from a highlight. When, by design, the distance from a
      highlight was uncoupled from the luminance value at corresponding probe points,
      the decrease in rated gloss correlated more with distance than with luminance
      change. Experiments also indicated that gloss ratings may change as a function of
      estimated surface distance, rather than as a function of image distance. Surface
      continuity affected gloss ratings, suggesting that surface and gloss processing
      are closely related.

PMID- 15991694
TI  - Global versus local image expansion in estimating time-to-contact from complex
      optic flow.
AB  - Previous work (Harris and Giachritsis 2000, Vision Research 40 601-611) has shown
      that, when global and local image expansion are placed in conflict, estimates of
      time-to-contact (TTC) are based almost exclusively upon global expansion. Here we
      extend this finding by demonstrating that global image expansion continues to
      predominate even under conditions that seem more favourable to a local analysis.
      We added a global rotation to the stimulus so that the global pattern of
      expansion was distorted while leaving the local expansion unaffected. Even under
      relatively high rotation rates (30 degrees s(-1)), local expansion continued to
      have little systematic effect upon estimates of TTC.

PMID- 15991695
TI  - Effects of the degree of fluctuation on subjective preference for a 1 Hz
      flickering light.
AB  - Humans are believed to have a preferred amount of stimulus variation in their
      perceptual environment. Here, paired comparison tests were conducted to examine
      whether the fluctuation of a flickering light improves subjective preference.
      Sine-wave and bandpass noise acted as the light source. We have previously shown
      that the preferred temporal frequency of a flickering light without any
      fluctuation is approximately 1 Hz (Soeta et al 2002 Journal of the Optical
      Society of America A 19 289 - 294). This was used as the center frequency of the
      light source. The bandwidth was set at 1, 2, 4, 8, and 16 Hz, to control the
      amplitude of the first peak of the autocorrelation function, phi1. Results show
      that the preferred phi1 of a flickering light is 0.46.

PMID- 15991696
TI  - Speaker variations influence speechreading speed for dynamic faces.
AB  - We investigated the influence of task-irrelevant speaker variations on
      speechreading performance. In three experiments with video digitised faces
      presented either in dynamic, static-sequential, or static mode, participants
      performed speeded classifications on vowel utterances (German vowels /u/ and
      /i/). A Garner interference paradigm was used, in which speaker identity was task
      irrelevant but could be either correlated, constant, or orthogonal to the vowel
      uttered. Reaction times for facial speech classifications were slowed by task
      irrelevant speaker variations for dynamic stimuli. The results are discussed with
      reference to distributed models of face perception (Haxby et al, 2000 Trends in
      Cognitive Sciences 4 223-233) and the relevance of both dynamic information and
      speaker characteristics for speechreading.

PMID- 15991697
TI  - Is synaesthesia an X-linked dominant trait with lethality in males?
AB  - In previous research the inheritance patterns of synaesthesia (eg experiencing
      colours from graphemes) has been studied and it was concluded that synaesthesia
      is most likely to be the outcome of a single gene passed on the X chromosome in a
      dominant fashion. In addition, it has been reported that the female-male ratio of
      synaesthetes is as high as 6:1 and the families of synaesthetes contain more
      female than male members. This raises the possibility that the gene may be
      associated with lethality in males. In this study we replicate and extend
      previous research by investigating the female-male ratio and inheritance patterns
      in a large sample of synaesthetic families (N = 85). We were able to verify the
      authenticity of grapheme-colour associates in at least one proband from each
      family using internal consistency. As before, our results show a female-male bias
      and are broadly consistent with an X-linked dominant mode of inheritance.
      However, there was no evidence of male lethality (eg synaesthetes are just as
      likely to give birth to sons as to daughters). Moreover, our female-male ratio of
      synaesthetes within families was 2:1--considerably lower than previous estimates.
      We speculate that men may be more reluctant to disclose synaesthesia than women
      (indeed, our female-male ratio based on self-referral was 3.7: 1). Finally, we
      discuss how the genotype may give rise to the phenotype in terms of changes in
      synaptogenesis or plasticity extending into childhood, to be subsequently shaped
      by the environment.

PMID- 15991698
TI  - Perceptual grouping in pigeons.
AB  - Animal studies reveal that many species perceive partially occluded objects in
      the same way as do humans. Pigeons have been a notable exception. We re
      investigated this anomaly of pigeon perception using a different approach from
      previous studies. With our method, we show that pigeons perceive occluded objects
      in the same manner as do other species. In addition, we report that pigeons can
      recognize perceptually transparent surfaces when the effect is induced by the
      same perceptual mechanisms as occlusion. These results give behavioral evidence
      that the perception of both occlusion and transparency is a common visual
      function shared by pigeons and humans, despite the structural differences between
      their visual systems.

PMID- 15991699
TI  - Kits, colours, and confusion: a pilot study of vision and football.

PMID- 15991700
TI  - Effects of differences in virulence of different serovars of Haemophilus
      paragallinarum on perceived vaccine efficacy.
AB  - The virulence of four South African field isolates of NAD-dependent Haemophilus
      paragallinarum and two field isolates of NAD-independent H. paragallinarum has
      previously been tested in unvaccinated chickens. In this study, the disease
      profiles caused by the NAD-dependent isolates of H. paragallinarum in vaccinated
      chickens were studied. It was shown that the clinical signs induced in the
      vaccinated chickens were substantially less severe than were those in
      unvaccinated chickens, as was expected. However, due to the high virulence of the
      serovar C-3 isolates, clinical signs in the vaccinated chickens challenged with
      this isolate were still detected. These were as severe as those occurring in
      unvaccinated chickens challenged with serovar B-1 isolates. Although the clinical
      signs induced in unvaccinated birds challenged with serovar A-1 were more severe
      than those occurring when vaccinated birds were challenged with serovar C-3, the
      overall disease profiles were similar. Substantial clinical signs were recorded
      in vaccinated birds challenged with serovar C-3. This could be interpreted as
      vaccination failure if the disease profile obtained in unvaccinated birds is not
      considered. It was found that a high level of protection was provided by this
      vaccine against challenge by serovar C-3. The high virulence of this serovar
      resulted in the development of clinical signs in vaccinated birds. These findings
      could possibly explain the large number of so-called vaccination failures that
      are reported in South Africa.

PMID- 15991701
TI  - Some preliminary observations on the susceptibility and resistance of different
      cattle breeds to Theileria parva infection.
AB  - Theileria parva-naive Friesian (Bos taurus), Boran (Bos indicus) and Maasai Zebu
      steers (B. indicus) were infected with a T. parva sporozoite stabilate dose which
      had previously been shown to induce an estimated 50% mortality rate in Boran
      cattle. All the cattle developed patent infections with no significant
      differences in the length of the prepatent period to development of
      macroschizonts (P > 0.05) between the three groups. Clinical theileriosis
      occurred in all eight the Friesians (100%), five out of nine Borans (55.6%) and
      two out of five Zebus (40%). Three of the Friesians (37.5%), and two of the
      Borans (22.2%) died of theileriosis. The different cattle types were equally
      susceptible to the infective dose used as indicated by the length of the
      prepatent periods, but there was a marked difference in their development of
      clinical theileriosis. The gradation in resistance to disease confirms the
      findings of earlier less critical studies and identifies these cattle breeds as
      suitable for investigations into the mechanisms of resistance to theileriosis.

PMID- 15991702
TI  - In vivo comparison of susceptibility between Bos indicus and Bos taurus cattle
      types to Theileria parva infection.
AB  - The objective of this study was to determine whether Bos taurus cattle differ
      form Bos indicus in their susceptibility to infection with the Muguga stabilate
      of Theileria parva and in their resistance to the resultant disease. Ten
      Friesians (B. taurus), ten improved Borans (B. indicus), ten unimproved Borans
      (B. indicus) and ten Zebus (B. indicus) born to dams from an East Coast fever
      (ECF) endemic area were inoculated with an infective dose50 dilution of T. parva
      Muguga stabilate 147. All the animals except one Friesian and one Zebu developed
      schizont parasitosis. All the improved Borans, nine of the Friesians, eight of
      the unimproved Borans and six of the Zebus developed a febrile response. Four of
      the improved Borans, four of the Friesians and three of the unimproved Borans
      died of theileriosis. No significant difference (P > 0.05) in the prepatent
      period occurred between the groups, but the Zebus had a significantly shorter
      duration of schizont parasitosis (P > 0.05) and took a significantly shorter time
      to recover (P > 0.05) than the other three groups. There was no significant
      difference in the two parameters between the other three groups. The study showed
      that three B. indicus breds and a B. taurus breed are equally susceptible to T.
      parva infection. However, Zebus born to dams from an ECF endemic area showed a
      better ability to control the course of disease than cattle from ECF free areas.

PMID- 15991703
TI  - Claviceps cyperi, a new cause of severe ergotism in dairy cattle consuming maize
      silage and teff hay contaminated with ergotised Cyperus esculentus (nut sedge) on
      the Highveld of South Africa.
AB  - During December/January 1996/97 typical summer syndrome (hyperthermia and a 30%
      drop in milk yield) occurred in succession in two Holstein dairy herds (n=240 and
      n=150 milking cows, respectively) on the South African Highveld. These farms are
      situated in the midst of the prime maize and dairy farming areas of South Africa
      where this condition had never been diagnosed before. The individual components
      of the concentrate on both farms were negative for ergot alkaloids. Endophytic
      fungi and/or ergot infestation of teff and other grasses fed to the cows were
      then suspected of being involved, but neither endophytes nor ergot alkaloids
      could be implicated from these sources. By measuring the serum prolactin levels
      of groups of sheep (n=5) fed the first farm's total mixed ration (TMR) or its
      three individual fibre components for a period of 11 days, the source of the
      ergot alkaloids was identified. A statistically significant decrease in the level
      of this hormone occurred only in the group on maize silage (which constituted 28%
      on dry matter base of the TMR). The involvement of the maize silage was further
      chemically confirmed by the high levels of total ergot alkaloids, predominantly
      ergocryptine, found by LC-MS in the silage as well as in the TMR (115-975 ppb and
      65-300 ppb, respectively). The ergot alkaloid content (mainly ergocryptine) of
      the maize silage on the second affected farm was 875 ppb. Withdrawal of
      contaminated silage resulted in gradual recovery of stock on both farms. Nut
      sedge (Cyperus esculentus and Cyperus rotundus of the family Cyperaceae) has a
      world-wide distribution and is a common weed in annual crops, and can be
      parasitized by Claviceps cyperi. Careful examination of the maize silage from
      both farms revealed that it was heavily contaminated with nut sedge and that it
      contained minute sclerotia, identified as those of Claviceps cyperi, originating
      from the latter. Nut sedge was abundant on both farms and it is believed that
      late seasonal rain had resulted in mature, heavily ergotised nut sedge being cut
      with the silage. Claviceps cyperi sclerotia, collected on the affected fields in
      the following autumn contained 3600-4000 ppm ergocryptine. That the dominant
      alkaloid produced by this particular fungus was indeed ergocryptine, was
      confirmed by negative ion chemical ionization MS/MS. In one further outbreak in
      another Holstein herd, teff hay contaminated with ergotised nut sedge and
      containing 1200 ppb alkaloids, was incriminated as the cause of the condition.
      This is the first report of bovine ergotism not associated with the Poaceae
      infected with Claviceps purpureum or endophytes but with the family Cyperaceae
      and this particular fungal phytopathogen.

PMID- 15991704
TI  - Toxicity, pathophysiology and pathology in sheep following dosing of the
      nephrotoxic plant Nolletia gariepina (DC) Mattf.
AB  - Ingestion of the plant Nolletia gariepina was confirmed as the cause of acute
      mortalities in cattle in the Kuruman area of the Northern Cape Province of South
      Africa. The aim of this trial was to investigate the toxic effects of this plant
      with respect to clinical signs, pathophysiology and pathology using the sheep as
      a model. At dosages of 1.5 g dried, milled plant material/kg body mass there were
      no detectable abnormal findings, while at dosages of 2.8-3.0 g/kg most of the
      animals died acutely. In subacutely affected sheep, depression, inappetance,
      teeth grinding, tachycardia, weak ruminal movements and recumbency were noticed.
      The most prominent pathophysiological changes observed, included a sharp rise in
      non-protein nitrogen substances in the plasma, remarkable decline in glomerular
      filtration rate, increase in sodium and potassium excretion, and a rise in urine
      gamma glutamyltransferase activity. Macroscopically a severe nephrosis was
      present in all the animals. The most important findings detected histologically
      were necrosis of the proximal convoluted tubular epithelium and large numbers of
      protein casts in the lumens.

PMID- 15991705
TI  - The systematic position of some Ethiopian Nippostrongylinae (Nematoda,
      Trichostrongylina, Heligmosomoidea) from the National Collection of Animal
      Helminths, Onderstepoort, South Africa.
AB  - The taxonomic status of some nippostrongyline nematodes deposited in the National
      Collection of Animal Helminths, Onderstepoort, is revised. Heligmonina boomkeri
      n. sp. is described from Aethomys chrysophilus from South Africa. The most
      closely related species by the body measurements and the pattern of the caudal
      bursa is Heligmonina bignonensis Diouf, Ba & Durette-Desset, 1997, a parasite of
      Mastomys erythroleucus from Senegal. It differs from the new species mainly in
      the number of ventral cuticular ridges at mid-body (four versus five) and the
      left ala in the male is shorter than the body diameter. The systematic position
      of Heligmonina spira (Ortlepp, 1939) and Neoheligmonella capensis (Ortlepp, 1939)
      is confirmed here through their synlophe, which was not previously studied.

PMID- 15991706
TI  - Epidemiological studies of amphistome infections in cattle in the highveld and
      lowveld communal grazing areas of Zimbabwe.
AB  - During the period between January 1999 and December 2000, the distribution and
      seasonal patterns of amphistome infections in cattle in the highveld and lowveld
      communal grazing areas of Zimbabwe were determined through monthly coprological
      examination. Cattle faecal samples were collected from 12 and nine dipping sites
      in the highveld and lowveld communal grazing areas, respectively. Patterns of
      distribution and seasonal fluctuations of intermediate host-snail populations and
      the climatic factors influencing the distribution were also determined by
      sampling at monthly intervals for a period of 24 months (November 1998 to October
      2000) in six dams and six streams in the highveld and in nine dams in the lowveld
      communal grazing areas. Each site was sampled for relative snail density and the
      vegetation cover and type, physical and chemical properties of water, and mean
      monthly rainfall and temperature were recorded. Aquatic vegetation and grass
      samples 0-1 m from the edges of the snail habitats were collected monthly to
      determine the presence or absence of amphistome metacercariae. Snails collected
      at the same time were individually checked for the emergence of larval stages of
      amphistomes. A total of 16,264 (calves 5418, weaners 5461 and adults 5385) faecal
      samples were collected during the entire period of the study and 4790 (29.5%) of
      the samples were positive for amphistome eggs. For both regions the number of
      animals positive for amphistome eggs differed significantly between the 2 years,
      with the second year having a significantly higher prevalence (P < 0.01) than the
      first year. Significantly higher prevalences were found in the highveld compared
      to the lowveld (P < 0.001), for adult cattle than calves (P < 0.01), and in the
      wet over the dry season (P < 0.01). Faecal egg output peaked from October to
      March in both years of the study. Bulinus tropicus, Bulinus forskalii and
      Biomphalaria pfeifferi were recorded from the study sites. The main intermediate
      host for amphistomes was B. tropicus with a prevalence of infection of 8.5%.
      However, amphistome cercariae were also recorded in Biom. pfeifferi and B.
      forskalii. Amphistome cercariae were recorded from both the highveld and lowveld
      areas with peak prevalence during the post-rainy season (March to May).
      Metacercariae were found on herbage from the fringes of the snail habitats
      between February and August, with most of the metacercariae concentrated on
      herbage 0-1 m from the edges of the habitats. Based on the epidemiological
      findings a control programme was devised. From this study, large burdens of
      immature flukes could be expected in cattle during the dry months. Since adult
      cattle would be resistant to the pathogenic effects of the migrating immature
      amphistomes the target for control would be young animals being exposed to the
      infection for the first time. Therefore, the first anthelmintic treatment can be
      administered in calves in mid June when maximum migration of immature amphistomes
      starting 3-4 weeks after infection in the early dry season would be expected. A
      second treatment could be given in late July or early August to remove
      potentially dangerous burdens of immature flukes acquired later in the dry
      season. Where resources permit, another strategy would be to treat against the
      mature flukes in March or April in order to reduce the number of eggs deposited
      on pastures and the opportunity for infection of the intermediate host snails. To
      reduce cercarial shedding by the intermediate host snails molluscicides can also
      be applied during the peak transmission periods (April/May and August/September).

PMID- 15991707
TI  - The performance of Orma Boran and Maasai Zebu crossbreeds in a trypanosomosis
      endemic area of Nguruman, south western Kenya.
AB  - Studies on the trypanotolerance of Orma Boran X Maasai Zebu (Orma Zebu) crossbred
      cattle (F1 progeny) and pure-bred Maasai Zebu contemporaries were carried out in
      Nguruman, south western Kenya. The two groups were monitored from birth for a
      period of 2 years. The incidence of trypanosomosis, parasitaemia, packed cell
      volume (PCV), body mass and average daily mass gain were monitored. During the
      study period, overall trypanosomosis incidence was low (3%). The crossbred cattle
      had a higher incidence of infection (61% vs 39%). The mean PCV and mean mass gain
      for the crossbred cattle was higher than that of the Maasai Zebu. The mean calf
      body mass at weaning (8 months) for the Orma Zebu and Maasai Zebu was 72 kg and
      64 kg, respectively, while at 18 months of age their mean body mass was 164 kg
      and 123 kg, respectively. During the rainy season significant differences in
      average daily mass gains were noted (P < 0.05). The superior mass gain of the
      Orma Zebu observed during the rainy season, despite higher infection rates,
      indicate an enhanced trypanotolerance. Moreover, the better performance of the
      Orma Zebu is an attribute that could be exploited in the adoption of the
      trypanotolerance genotype, as a sustainable trypanosomosis control strategy.

PMID- 15991708
TI  - Importation of canid rabies in a horse relocated from Zimbabwe to South Africa.
AB  - In July 2003 a 2-year-old Thoroughbred colt was imported from Harare, Zimbabwe to
      the Ashburton Training Centre, Pietermaritzburg, South Africa. Five months after
      importation, the colt presented with clinical signs suggestive of rabies: it was
      uncoordinated, showed muscle tremors and was biting at itself. Brain tissue was
      submitted for analysis and the clinical diagnosis was confirmed by the
      fluorescent antibody test and reverse-transcription polymerase chain reaction (RT
      PCR). Phylogenetic analysis of the nucleotide sequence of the cytoplasmic domain
      of the glycoprotein and the G-L intergenic region of the rabies virus confirmed
      it to be an infection with a canid rabies virus, originating from an area in
      Zimbabwe endemic for the domestic dog (Canis familiaris) and side-striped jackal
      (Canis adustus) rabies.

PMID- 15991709
TI  - Serological evidence of chicken anaemia virus infection in Nigerian indigenous
      chickens.
AB  - Serum samples from 20 out of 180 (11.1%) apparently healthy Nigerian indigenous
      chickens were negative for antibodies against chicken anaemia virus using the
      enzyme-linked immunosorbent assay (ELISA). Of the 160 positive sera (88.9%), 12
      (7.5%) had titres ranging from 1500-3000, 46 (28.8%) had titres from 3000-5000
      while 102 (63.8%) had titres between 5000-11000. The overall mean titre value was
      5845 +/- 2402. This appears to be evidence of a natural outbreak of the infection
      since the chickens had no history of vaccination against any poultry disease.

PMID- 15991710
TI  - [Contemporary medical and demographic situation in Russia].
AB  - The article presents data on public health state in Russia over past years.
      Analysis of medical, demographic parameters, morbidity values proves continuing
      deterioration of public health state in Russia.

PMID- 15991711
TI  - [State of neuro-humoral regulation in workers with intensive psychologic strain].
AB  - Acitvities of internal affairs officers are associated with law machinery and
      power establishment and therefore carry prolonged psychoemotional strain.
      Necessity of higher occupational ability and reliability of internal affairs
      officers in significant functional strain determines importance and expedience of
      studying responses, adaptational mechanisms and their break in these individuals.

PMID- 15991712
TI  - [Evaluating influence of individual protective means on heat state of individuals
      working in heating microclimate].
AB  - The authors evaluate working clothes protecting against electromagnetic waves and
      chemical pollution to exemplify that the clothes use in heating surroundings
      deteriorates human heat state due to disordered heat-mass exchange with
      environment and higher physical exertion caused by the clothes weight. The
      article demonstrates necessity to correct requirements to microclimate
      parameters, if using working clothes deteriorating heat-mass exchange with
      environment in heating microclimate. For adequate evaluation of work conditions,
      the materials include temperature modification values in accordance with some
      working clothes types.

PMID- 15991713
TI  - [Diagnostic value of needle electromyography in patients with occupational
      polyneuropathy caused by vibration and functional overstrain].
AB  - The authors determined diagnostic and differential value of needle
      electromyography in workers with occupational diseases of upper limbs. Results
      prove differences in neuromotor disorders of hands: vibration disease usually
      involves spinal motoneurons, whereas functional overstrain is characterised by
      marked muscular suffering (myopathy, myodystrophy).

PMID- 15991714
TI  - [State of protease inhibitor system in patients with occupational bronchial
      asthma caused by nonferrous metal aerosols].
AB  - The article represents results of studies concerning biochemical features of
      inflammation in various types of bronchial asthma caused by nonferrous metal
      aerosols. Also parameters of "proteolysis--antiproteolysis" system were studied
      on molecular genetic and biochemical levels, with determining serine proteinase,
      level of protease alpha-1 inhibitor and its hyposecretory deficit variants,
      levels of individual proteins.

PMID- 15991715
TI  - [Problem of occupational risk criteria and of evaluating compensations for
      workers].
AB  - The article covers problem of occupational risk criteria and compensation of
      health damage, with consideration of domestic and international experience.

PMID- 15991717
TI  - [Electric fields of industrial frequency and their influence on humans].

PMID- 15991716
TI  - [Arterial hypertension and ischemic heart disease in workers exposed to local
      vibration].
AB  - The article presents data on prevalence of arterial hypertension and
      ischemicheart disease in workers exposed to vibration, both having vibration
      disease and free of it.

PMID- 15991718
TI  - [Blood cells in vitro exposed to low-intensity electric inrush currents of
      industrial frequency].

PMID- 15991719
TI  - [Influence of infrasound on lymphatic drainage state].

PMID- 15991720
TI  - Use of flow injection and sequential injection analysis schemes for the
      determination of trace-level concentrations of metals in complex matrices by
      ETAAS and ICPMS.
AB  - Despite their excellent analytical chemical capacities for determination of low
      levels of metal species, electrothermal atomic absorption spectrometry and
      inductively coupled plasma mass spectrometry often require suitable pretreatment
      (separation and preconcentration) of the sample material to facilitate the
      desired sensitivity and selectivity of measurement. Such pretreatment schemes are
      advantageously performed in flow injection (FI) or sequential injection (SI)
      manifolds, where all unit operations can be effected on-line and under enclosed
      and strictly controlled conditions. Various separation/preconcentration
      procedures are feasible, such as liquid-liquid extraction (possibly including
      back extraction), (co)precipitation with collection in knotted coils, adsorption
      on hydrophilic or hydrophobic reactors, hydride generation, or the use of ion
      exchange/chelating packed columns. After describing the particulars and
      characteristics of FI and SI, we present, via selected examples, various
      separation/preconcentration FI/SI schemes for the determination of trace levels
      of metals, with particular emphasis on the use of the novel extension of FI/SI,
      that is, the so-called lab-on-valve concept.

PMID- 15991721
TI  - Comparison of several toxicity tests applied to complex wastewaters and mussel
      biomarkers in receiving waters.
AB  - In this study, the complex wastewaters/effluents discharged to coastal regions of
      Turkey and Greece were sampled, and various toxicity tests were applied. The
      bioassays used included the assessment of the luminescence inhibition of the
      bacterium Vibrio fisheri, the photosynthesis inhibition (14C uptake rate) and
      growth inhibition of the algal species Phaeodactylum tricornutum, and the
      mortality of the crustacean Artemia franciscana and rotifer Brachionus
      plicatilis. Additionally, "neutral red retention" and "filtration rate" sublethal
      biomarker techniques were performed by utilizing the mussel species Mytilus
      galloproviancialis, inhabiting the points of discharges in Turkey. All discharges
      tested were found to be acutely toxic to P. tricornutum and slightly toxic to V.
      fisheri, A. franciscana, and B. plicatilis. Test results showed that the 14C
      uptake rate toxicity test was the most sensitive one among the other bioassays.
      The biomarker results showed that the health status of mussels in the coastal
      areas decreased significantly, indicating the pollution of the receiving waters
      in Turkey. The conclusions drawn highlight the necessity for an intesive
      ecotoxicological monitoring scheme that will incorporate the most suitable
      bioassays and biomarkers to adequately contribute to the upgrading and
      maintenance of the ecological quality of the coastal waters in Greece and in
      Turkey.

PMID- 15991722
TI  - Kinetics of trihalomethane formation from organic contaminants in raw water from
      the Bangkhen water treatment plant.
AB  - The fractionation of raw water from Bangkhen water treatment plant, Bangkok,
      Thailand revealed that the mass distribution sequence of the six organic
      fractions from high to low was hydrophilic neutral (HPIN), hydrophobic acid
      (HPOA), hydrophilic acid, hydrophobic neutral, hydrophilic base, and hydrophobic
      base. The main organic matter components in raw water were HPIN and HPOA, which
      were also the two most important contributors of trihalomethane formation
      potential (THMFP). Linear dependencies between the level of each organic fraction
      and the formation potential of THM species were observed, which suggested the
      reactions between the organic fraction and chlorine during the chlorination were
      first order. The fractionation led to a deviation of bromide concentration in
      each organic fraction from the original concentration, and this affected the
      formation of brominated THM species. However, this effect was demonstrated to be
      within an acceptable range. The chlorination of an individual organic fraction
      resulted in a higher level of THMFP than that of the raw water and mixed
      fractions, indicating an inhibitory effect between the organic species.

PMID- 15991723
TI  - Pyrolysis of foundry sand resins: a determination of organic products by mass
      spectrometry.
AB  - Pyrolysis-gas chromatography-mass spectrometry (MS) was used to identify the
      major organic products produced by pyrolysis of three foundry sand resins: (i)
      Novolac and (ii) phenolic urethane (PU) (both phenol-formaldehyde based resins)
      and (iii) furan (furfuryl alcohol based resin). These resins are used in the
      metal casting industry as a "sand binder" for making cores (used to produce
      cavities in molds) and molds for nonferrous castings. During the casting process,
      the cores and molds are subjected to intense heat from the molten metal. As a
      result, the organic resins undergo thermal decomposition and produce a number of
      complex organic compounds. In this study, the organics were tentatively
      identified by MS after pyrolysis of the resins at 750 degrees C. The major
      thermal decomposition products from the Novolac, PU, and furan resins were
      derivatives of phenol, benzene, and furan, respectively. Compounds identified
      that are of potential environmental concern were benzene, toluene, phenol, o- and
      p-xylene, o- and m-cresol, and polycyclic aromatic hydrocarbons. Pyrolysis of the
      Novolac resin resulted in the generation of the most compounds of environmental
      concern. Because there is interest in beneficially using foundry molding sands in
      manufactured soils and other agricultural products, it is necessary that organic
      thermal decomposition products be identified to ensure environmental protection.

PMID- 15991724
TI  - Potential waste minimization of trichloroethylene and perchloroethylene via
      aerobic biodegradation.
AB  - Trichloroethylene (TCE) and perchloroethylene (PCE) are two of the most
      frequently detected chlorinated organics found in groundwater. Biodegradation
      with a new aerobic consortium was used to ascertain the viability of
      bioremediation for waste minimization applications. After 1 week of treatment,
      the degradation rate constants, k, were between 0.004 and 0.012 d(-1) for initial
      concentrations of 54-664 microM TCE. When PCE was used as the sole contaminant,
      the k values were approximately 0.01 d(-1) regardless of the initial
      concentration. The addition of 0.2 microM toluene or phenol as an inducer
      dramatically increased TCE degradation. For instance, at 200 microM TCE the k
      value when toluene was added (0.03 d(-1)) was 2.2 times higher than without
      inducers (0.009 d(-1)). The addition of 0.2 microM phenol increased the rate
      constant by 58%. However, PCE degradation rates were not changed significantly.

PMID- 15991725
TI  - Removal of phenolic compounds in water by ultrafiltration membrane treatments.
AB  - The ultrafiltration (UF) of aqueous solutions containing mixtures of three
      phenolic compounds (gallic acid, acetovanillone, and esculetin) was studied in a
      tangential UF laboratory system. These substances were selected as model
      pollutants present in the tannic fraction of the cork processing wastewaters. The
      two membranes used were a polyethersulfone membrane (Biomax5K) and a regenerated
      cellulose membrane (Ultracel5K), both with a molecular weight cut-off (MWCO) of
      5000 Da. Previous experiments for the characterization of the membranes led to
      values for the water hydraulic permeability of 70.3 and 18.1 L/h x m2 x bar for
      the Biomax5K and Ultracel5K membranes, respectively. During the UF experiments,
      the permeate flow rate remained almost constant with processing time and the
      evolution of the pollutants concentrations varied depending on the nature of the
      membranes and the substances. The influence of the main operating variables
      (tansmembrane pressure and feed flow rate) on the permeate flux was established,
      and values for the apparent and intrinsic rejection coefficients were evaluated.
      Cork processing wastewater UF experiments were also conducted under similar
      operating conditions to those applied to the ultrapure water solutions. Removals
      of chemical oxygen demand, aromatic and tannic contents, and color were
      determined in these experiments, and the elimination of the three model compounds
      in the wastewater was also followed, with the evaluation of their apparent
      rejection coefficients.

PMID- 15991726
TI  - Immobilization of TiO2 nanopowder on glass beads for the photocatalytic
      decolorization of an azo dye C.I. Direct Red 23.
AB  - TiO2 supported on glass beads was prepared and its photocatalytic activity was
      determined by photooxidation of the commercial textile dye, C.I. Direct Red 23,
      in aqueous solution illuminated by a UV-C lamp (30 W). The progress of
      photocatalytic decolorization of the C.I. Direct Red 23 was studied by measuring
      the absorbance at lambda(max) = 507 nm by UV Vis spectrophotometer. The
      experiments indicated that both UV light and TiO2 were needed for the effective
      destruction of the dye. The effect of pH on the rate of decolorization efficiency
      was followed in the pH range 2-12. Acidic pH range was found to favor the
      decolorization rate. The addition of a proper amount of hydrogen peroxide
      improved the decolorization, whereas the excess hydrogen peroxide quenched the
      formation of hydroxyl radicals (*OH). The electrical energy consumption per order
      of magnitude for photocatalytic decolorization of the dye was lower in the
      UV/TiO2/H2O2 process than that in the UV/TiO2 process. In the real wastewater
      sample the efficiency of the method was determined by measuring the changes in
      the absorption spectra of the dye solution during photodegradation. Our results
      indicated that during the photooxidation process, the decolorization efficiency
      was more than 80% at irradiation time of 3 h.

PMID- 15991727
TI  - The efficiency of a sequencing batch biofilm reactor in organic carbon and
      phosphorus removal.
AB  - A laboratory sequencing batch biofilm reactor (SBBR), operated for a period of
      158 days, was used to treat domestic-strength synthetic effluent. The biofilm
      reactor comprised a bulk fluid reactor, a biofilm plastic module, a synthetic
      wastewater feed tank, and pneumatic devices with pneumatic controls. The reactor
      cycle time was 8 h, and its operation consisted of five phases: feeding (59 min),
      mixing (1 min), anoxic/anaerobic (3 h), aerobic (3 h), and settling (1 h). At
      total chemical oxygen demand (CODT) loading rates of 8.8 g CODT m(-2) d(-1) and
      1.2 kg CODT m(-3) d(-1), expressed in terms of the plastic module surface area
      and reactor volume, respectively, the SBBR had average removal rates of 8.3 g
      CODT m(-2) d(-1) and 1.1 kg CODT m(-3) d(-1), or 94%. Total orthophosphorus (PO4
      PT) and filtered orthophosphorus (PO4-PF) removals were 44% and 50%,
      respectively.

PMID- 15991728
TI  - Alkaline hydrothermal conversion of fly ash filtrates into zeolites 2:
      utilization in wastewater treatment.
AB  - Filtrates were collected using a codisposal reaction wherein fly ash was reacted
      with acid mine drainage. These codisposal filtrates were then analyzed by X-ray
      Fluorescence spectrometry for quantitative determination of the SiO2 and Al2O3
      content. Alkaline hydrothermal zeolite synthesis was then applied to the
      filtrates to convert the fly ash material into zeolites. The zeolites formed
      under the experimental conditions were faujasite, sodalite, and zeolite A. The
      use of the fly ash-derived zeolites and a commercial zeolite was explored in
      wastewater decontamination experiments as it was applied to acid mine drainage in
      different dosages. The concentrations of Ni, Zn, Cd, As, and Pb metal ions in the
      treated wastewater were investigated. The results of the treatment of the acid
      mine drainage with the prepared fly ash zeolites showed that the concentrations
      of Ni, Zn, Cd, and Hg were decreased as the zeolite dosages of the fly ash
      zeolite (FAZ1) increased.

PMID- 15991729
TI  - Suspended sediment removal by vegetative filter strip treating highway runoff.
AB  - Structural best management practices (BMPs) are often used to mitigate the impact
      of storm water runoff on receiving waters. Vegetative filter strips (VFS) are an
      example of a structural BMP that has been used to treat storm water and highway
      runoff. Physical factors affecting the performance of VFS include pollutant
      characteristics, vegetation composition and density, soil properties, and the
      physical dimensions of the filter strip. In this study, field-suspended sediment
      data were collected from an experimental VFS treating highway runoff in eastern
      North Carolina. Field data were used to test the design concepts of the VFS
      treatment train and to validate a simulation model for evaluating the impact of
      these physical factors on sediment removal as a function of filter strip length.
      It was concluded that the experimental filter strip was effective in removing
      more than 85% of the incoming total suspended sediment (TSS). Simulation results
      support field observations that a 10-m or longer filter strip can retain most of
      the medium and large particles (> 8 microm) transported in runoff. Simulations
      also indicate infiltration loss is largely responsible for the retention of small
      size sediment particles (< 8 microm). Saturated hydraulic conductivity and
      initial water contents have little effects on TSS removal. The condition of
      vegetative coverage, in particular vegetation density, is another factor
      affecting the performance of filter strip.

PMID- 15991730
TI  - [On the psychiatric examination of fire-raisers].
AB  - By far not every fire-raiser suffers from so-called pyromania, i.e. a
      pathological urge to raise fire. It is indispensable to differentiate between
      extrinsic and intrinsic motivation, whenever a person is accused of arson. The
      former aims at external gain, such as the sum insured, while the latter tends
      towards manipulation of internal states. The leading motive may be frustration,
      fascination, or in rare cases even sexual arousal. The concept of pyromania, as
      established by French psychiatrist Esquirol, is not a validated one in all parts;
      today's diagnostic manuals take "pyromania" rather as a special form of a general
      disorder of impulse control. The author takes a case report to demonstrate the
      most important issues in evaluating and prognosticating fire raising behavior.

PMID- 15991731
TI  - [Homicides with postmortal emasculation of the victim].
AB  - Among criminal offences with mutilation of the genitals the number of cases with
      isolated removal of the testicles is small. This paper describes two homicides
      with postmortal emasculation of the victim from the autopsy material of the
      Berlin Institute of Legal Medicine (Humboldt University). In both of them no
      further mutilation had been committed. Yet the perpetrator's motivation was
      different in the two cases. In one case the cut-off testicles had been concealed
      in the victim's mouth, an act never described anywhere before. Obviously the
      offender wanted to mislead the police in their investigations. In the second case
      the motivation was of a homosexual nature and was thus comparable to previously
      described cases.

PMID- 15991732
TI  - [Pneumatic spaces of the zygomatic arch (zygomatic air cell defect) on
      pantomograms--an aid for age determination and identification].
AB  - The analysis of panoramic radiographs of the jaws for forensic purposes is well
      established. The dental findings on the radiographs give valuable information
      concerning the identity and possible age. Panoramic radiographs also depict the
      zygomatic arches. Pneumatized spaces of the temporal bone's zygomatic arch
      process are asymptomatic variations, entitled "zygomatic air cell defect" (ZACD).
      Data on ZACD prevalence might support the current forensic-odontologic practice
      in the fields of identification and age assessment. The authors analyzed 6
      studies subjected to evaluate ZACD on panoramic radiographs. The out-patients
      were subjected to systematic radiography prior to treatment planning in
      specialized dental or maxillofacial surgery clinics. The age of the 7870 patients
      varied between 6 and 97 years. ZACD was found in 169 patients (prevalence: 2.32%;
      female: 56.12%, male: 43.9%). Most ZACD were unilateral (70%). In these studies
      no ZACD occurred in children younger than 7 years of age. There was no
      statistically significant difference concerning ZACD prevalence in the sub-groups
      of children aged 9 to 13 vs. 14 to 17 years. This review demonstrates the
      prevalence of ZACD on orthopantomograms. The prevalence of this finding in the
      investigated children does not differ from the prevalences reported for adults,
      and is low in general. The presence of ZACD in persons might be valuable for the
      identification of humans or human remains and for age estimation in addition to
      other physical and dental findings.

PMID- 15991733
TI  - [Fatal intoxication with amisulpride and presentation of organ distribution].
AB  - Amisulpride is a substituted benzamide used as an atypical antipsychotic drug. It
      antagonizes dopamine D2 and D3 receptor-mediated effects with greater affinity
      for the limbic system suggesting better neurological tolerance than classical
      neuroleptics. However, occasionally amisulpride intoxications associated with
      seizures, comatose conditions and agitation, hyperthermia, tachycardia,
      prolongation of the QT interval and extrapyramidal features have been described.
      A 27-year-old female with a medical history of psychosis and amisulpride therapy
      was found dead at home. By means of high performance liquid chromatography
      coupled with mass spectrometry (LC/MS) an amisulpride concentration of 13.4 mg/l
      was found in the peripheral blood. A lower concentration in the brain and an
      extremely high concentration in bile can be explained by the polarity and
      hydrophobic character of the substance. After macroscopic and histological
      exclusion of other causes of death the results of the toxicological analysis were
      consistent with the assumption of a fatal amisulpride overdose.

PMID- 15991735
TI  - [Coxibs in treatment and prevention of cancer].

PMID- 15991734
TI  - [The numerical Hatze-model: also qualified for calculations on children?].
AB  - The aim of this study was to find out whether the Hatze-model, which is
      specifically designed for adults, is suitable for calculations on children as
      well. By means of that program it is possible to calculate various parameters of
      the human body. After the collection of data and analysis of the results
      according to Hatze it becomes evident that this model provides good results only
      for the calculation of the total body mass. As regards the body segments, there
      are significant under- and overestimations. The same applies to the calculation
      of mean body density. Indeed there is a significant gender dimorphism indicating
      that girls have a higher fraction of body fat than boys. However, the values are
      far below those described in the literature. Due to the formula, the values of
      the centres of gravity are linear and congruent in both sides of the body.
      Interpretation of the results is difficult, as there are no valid reference
      values. Furthermore the program is not able to take characteristic shapes and
      proportions of children into account. For this reason 88% of the children are
      defined as either pregnant or obese. In summary, the study shows that the present
      model should not be used to calculate children and the human models have to be
      designed specifically for children.

PMID- 15991736
TI  - [Doping and sports - what is the problem?].

PMID- 15991737
TI  - [Competition in the health care system].

PMID- 15991738
TI  - [Allergic rhinitis].

PMID- 15991739
TI  - [What is the etiology of sciatica?].

PMID- 15991740
TI  - [Freezing of a girl's ovary tissue].

PMID- 15991741
TI  - [Pregnancy, window to women's health].

PMID- 15991742
TI  - [Cachexia].

PMID- 15991743
TI  - [Old traditional names of diseases in Finnish language].

PMID- 15991744
TI  - [Diagnosis and treatment of acute torsion and wandering spleen].

PMID- 15991746
TI  - [Epistaxis and dizziness].

PMID- 15991745
TI  - [Update on current care guidelines. Deep thrombosis and pulmonary embolism].

PMID- 15991747
TI  - [Cold induced changes in EKG].

PMID- 15991748
TI  - [Forgotton serological tests for diagnosis of dyspepsia in patients].

PMID- 15991749
TI  - [Noradrenaline and proprioception in spinal cord].

PMID- 15991750
TI  - [Captain Cook used sauerkraut to prevent scurvy].

PMID- 15991751
TI  - Medicare drug cards: where are the savings?

PMID- 15991753
TI  - Canadian pharmacies: usurping local pharmacists' roles in medication safety.

PMID- 15991754
TI  - Medicare Part D: opportunities and challenges for pharmacy.

PMID- 15991755
TI  - Comparison of costs of community and mail service pharmacy.
AB  - OBJECTIVE: To compare the costs of prescriptions dispensed through mail service
      and community pharmacies to quantify the comparative costs of the two types of
      pharmacies. DESIGN: Modeling study based on 1-year of claims data from a cohort
      of patients. SETTING: A health plan in the northeastern United States. PATIENTS:
      Approximately 100,000 members of the health plan. INTERVENTION: The plan used a
      small pharmacy benefits manager (PBM) and a mail service pharmacy that was not
      owned by a major PBM, a three-tier benefit design, and specified that patients
      could get a 90-day supply through mail service for the equivalent of two 30-day
      community pharmacy copayments. MAIN OUTCOME MEASURES: Actual total, ingredient,
      plan, and patient costs of prescriptions dispensed through a mail service
      pharmacy and the estimated costs of those same prescriptions at community
      pharmacies. RESULTS: Total costs for the 44,847 prescriptions dispensed through
      mail service were dollar 6,401,624. Had these prescriptions been dispensed at
      community pharmacies, costs would have been dollar 6,902,252. Ingredient costs
      were dollar 6,401,624 through mail versus dollar 6,633,170 at community
      pharmacies. Total costs to the health plan were dollar 4,726,637 through mail
      versus dollar 4,417,733 at community pharmacies. Member costs were dollar
      1,674,987 through mail versus dollar 2,484,519 at community pharmacies.
      CONCLUSION: Compared with community pharmacies, the mail service pharmacy was
      less expensive overall, less expensive for patients, but more expensive to the
      health plan. From the health plan's perspective, the loss of copayments in the
      mail service benefit was greater than the savings on ingredient costs and
      dispensing fees.

PMID- 15991756
TI  - Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient
      collaboration.
AB  - OBJECTIVE: To explore the impact of telephone-based education and monitoring by
      community pharmacists on multiple outcomes of pharmacist-patient collaboration.
      DESIGN: A randomized, controlled, unblinded, mixed experimental design. SETTING:
      Eight Wisconsin community pharmacies within a large managed care organization.
      PATIENTS: A total of 63 patients presenting new antidepressant prescriptions to
      their community pharmacies. INTERVENTIONS: Patients were randomized to receive
      either three monthly telephone calls from pharmacists providing pharmacist-guided
      education and monitoring (PGEM) or usual pharmacist's care. Usual care is defined
      as that education and monitoring which pharmacists may typically provide patients
      at the study pharmacies. MAIN OUTCOME MEASURES: Patient's frequency of feedback
      with the pharmacist, antidepressant knowledge, antidepressant beliefs,
      antidepressant adherence at 3 and 6 months, improvement in depression symptoms,
      and orientation toward treatment progress. RESULTS: Of the 60 patients who
      completed the study, 28 received PGEM and 32 received usual pharmacist's care.
      Results showed that PGEM had a significant and positive effect on patient
      feedback, knowledge, medication beliefs, and perceptions of progress. There were
      no significant group differences in patient adherence or symptoms at 3 months;
      however, PGEM patients who completed the protocol missed fewer doses than did the
      usual care group at 6 months (P < or = .05). CONCLUSION: Antidepressant
      telemonitoring by community pharmacists can significantly and positively affect
      patient feedback and collaboration with pharmacists. Longer-term studies with
      larger samples are needed to assess the generalizability of findings. Future
      research also needs to explore additional ways to improve clinical outcomes.

PMID- 15991757
TI  - Community pharmacist-child medication communication: magnitude, influences, and
      content.
AB  - OBJECTIVE: To describe community pharmacist-child medication communication with
      respect to its magnitude, influences, and content. DESIGN: Cross-sectional
      descriptive study. SETTING: Indiana. PARTICIPANTS: 460 community pharmacists.
      INTERVENTION: Mailed questionnaire was used for data collection. Sections
      included: (1) pharmacists' practice of medication communication with children and
      with adults; (2) factors influencing the pharmacist's decision to communicate
      with children about medications; (3) elements of pharmacist-parent and pharmacist
      child communication; and (4) demographics. MAIN OUTCOME MEASURE: Daily percentage
      of children to whom pharmacists talked directly about medications. RESULTS:
      Response rate was 44.7% with no indications of nonresponse bias. Most respondents
      were staff pharmacists in chain pharmacies. On average, pharmacists reported
      engaging in communications about medications with 20.7% of children and 57.0% of
      adults on a daily basis (t = 23.5, P < or = .0001). Experience as a preceptor and
      prescription volume significantly influenced the frequency of pharmacists'
      communication with either adults or children. Pharmacists provided more
      medication information to parents than to their children, and more medication
      information to older children than to younger children. Children of all ages were
      likely to be comforted and given information about the medicine's taste.
      CONCLUSION: Preliminary insights into the interaction between pharmacists and
      child patients are provided by this study. Considering the relatively low
      frequency of pharmacist-child communication, interventions aimed at influencing
      the child's and caregiver's motivation to seek information about the child's
      care, and improving pharmacist's knowledge about children's cognitive development
      at various ages may enhance the involvement of children in self-treatment.

PMID- 15991758
TI  - Consumers' perceptions about risk of and access to nonprescription medications.
AB  - OBJECTIVES: To examine how consumers balance the principles of safety with
      regulatory access to pharmaceuticals and to identify respondent characteristics,
      including prior misuse of nonprescription medications, that are associated with a
      preference for nonprescription status. DESIGN: Cross-sectional survey within
      subject attitudinal analysis. SETTING: Large midwestern metropolitan region of
      the United States. PARTICIPANTS: Convenience sample of 553 members of the general
      public. INTERVENTIONS: Anonymous self-administered surveys with hypothetical
      vignettes in which a heartburn or antihypertensive drug could be available
      without a prescription but in doing so would entail an increased risk (1/100,000,
      1/10,000, or 1/1,000 chance of heart attack) to the user that would not be
      present with the medical care afforded by prescription drug status. MAIN OUTCOME
      MEASURE: Proportion of respondents preferring nonprescription availability.
      RESULTS: Overall, 33%, 19%, and 11% of respondents preferred nonprescription
      availability when the additional risks of a heart attack with nonprescription
      availability were 1/100,000, 1/10,000, and 1/1,000, respectively. Risk tolerance
      did not differ between the heartburn and antihypertensive vignettes. Although
      preference for nonprescription status was significantly greater among respondents
      who were men (42% versus 28%) and white (42% versus 32%), and a statistical trend
      was evident among respondents with higher self-reported health (37% versus 27%)
      and a college education (36% versus 28%), most of these differences did not
      persist on multivariate analysis. CONCLUSION: A substantial minority of the
      public appears willing to accept considerable risk to gain greater access to
      pharmaceuticals. Heterogeneity among the general public with regard to how safety
      and access to nonprescription medications should be balanced challenges policy
      makers working to design responsive yet appropriate regulatory policies.

PMID- 15991759
TI  - Factors leading patients to discontinue multiple sclerosis therapies.
AB  - OBJECTIVES: To determine the percentages of patients who discontinued treatment
      with the multiple sclerosis medications intramuscular interferon beta-1a (IFN
      beta-1a; Avonex-Biogen), interferon beta-1b (IFN-beta-1b; Betaseron-Berlex), and
      glatiramer acetate (Copaxone-Teva) and to determine the factors that led to
      discontinuation of the medications. DESIGN: Cross-sectional study. SETTING:
      University-based neurology clinic. PATIENTS: 108 patients with multiple sclerosis
      who were prescribed intramuscular interferon beta-1a, subcutaneous interferon
      beta-1b, or subcutaneous glatiramer acetate. INTERVENTION: Telephone survey. MAIN
      OUTCOME MEASURES: Discontinuation percentages and the factors that contributed to
      discontinuation. RESULTS: There was no significant difference between the
      percentages of patients who discontinued and did not restart treatment with the
      products (interferon beta-1b, 41%; intramuscular interferon beta-1a, 34%; and
      glatiramer acetate, 28%). Four main reasons for medication discontinuation
      emerged: adverse effects (52%), physician-documented disease progression (40%),
      patient perception of drug ineffectiveness (20%), and cost (4%). No statistical
      differences were identified among the three agents for any of the reasons for
      discontinuation. CONCLUSION: Patient education on adverse effects and realistic
      patient expectations may be potential areas of study to improve discontinuation
      percentages with these agents.

PMID- 15991760
TI  - Becoming 'indispensable': developing innovative community pharmacy practices.
AB  - OBJECTIVE: To describe common characteristics of successful innovative community
      pharmacy practices. DATA SOURCES: Four pharmacists who are successfully
      incorporating pharmaceutical care services into their pharmacy practices were
      identified for inclusion by key informants. Sites considered for inclusion were
      within 300 miles of the University of Minnesota College of Pharmacy. The four
      innovative community pharmacy practices were located in Maquoketa, Iowa, and in
      Bemidji, Anoka, and Minneapolis, Minn. Published articles identified through a
      Medline search-using the terms pharmaceutical care, Medicaid, Medicare,
      pharmacist, pharmacy, and collaborative practice-provided information to prepare
      for pharmacist interviews. STUDY SELECTION: By the authors. DATA EXTRACTION:
      Previsit telephone interviews with each pharmacist, combined with literature
      selected by the authors, were used to identify common characteristics of
      successful practices. Structured, on-site empirical observation was then
      performed to devise a tool for pharmacists to use for the development of
      innovative community pharmacy practices. The tool was then validated by two
      additional practitioners. DATA SYNTHESIS: Components of successful innovative
      community pharmacy practices include philosophy of practice, patient care
      process, management system, and clinical knowledge. A checklist tool is presented
      to be used in conjunction with the narrative description of the four components.
      CONCLUSION: Advanced pharmacy services delivered within pharmaceutical care
      practices can be a successful business opportunity for community pharmacists.
      Community pharmacists motivated to develop an innovative practice and provide
      pharmaceutical care services can use the checklist tool during practice
      implementation.

PMID- 15991761
TI  - Developing a mobile pharmacist-conducted wellness clinic for rural Montana
      communities.
AB  - OBJECTIVE: To describe pharmacist-conducted disease screening services in remote
      communities. SETTING: Frontier, rural, and nonrural counties throughout western
      Montana. PRACTICE DESCRIPTION: Using federal telehealth funds, a motor home was
      converted into a mobile office and equipped with a satellite
      transmitting/receiving dish to provide wireless Internet access. The pharmacist
      uses an ultrasound unit to test heel bone density, a spirometer to test lung
      function, and appropriate analyzers to measure A1C and serum lipid levels.
      Screening clinics are held in conjunction with county health departments, tribal
      health authorities, community pharmacies, county agricultural extension agents,
      and Federally Qualified Health Centers. Employee wellness clinics are also
      conducted. Student pharmacists assist with screenings. PRACTICE INNOVATION:
      Mobile pharmacist-conducted disease screening clinics in remote communities. MAIN
      OUTCOME MEASURES: Number of communities served, number of patients screened,
      percentage of test results out-of-range/patients referred to their primary health
      care providers for follow-up, number of student pharmacists participating, and
      total revenues generated. RESULTS: During the first 2 years of the project,
      IPHARM pharmacists traveled approximately 14,000 miles, conducted 72 clinics in
      17 counties and performed 5,100 screening tests for more than 3,100 people.
      Approximately 36% of all screening test results were outside of expected range.
      More than 80 student pharmacists, most of whom were on clinical rotations,
      participated in the clinics and 11 community pharmacists have been trained to
      conduct screenings. In excess of dollar 70,000 was generated by the project in
      operating revenue and donations. At the conclusion of IPHARM's first year of
      operations, the motor home was taken out of service because of the cost of
      gasoline, difficulties of winter travel with such a large vehicle, and the
      realization that virtually all host organizations were able to provide space in
      which the screening clinics could be conducted. CONCLUSION: Pharmacists and
      student pharmacists are capable of providing disease screening services in remote
      frontier and rural communities. Obtaining sufficient payment for these services
      in rural communities to cover costs remains a challenge.

PMID- 15991762
TI  - Integration of a clinical community pharmacist position: emphasis on workflow
      design.
AB  - OBJECTIVE: To design and implement a scope of practice for a clinical pharmacist
      position and assess the clinical and economic impact of a Diabetes Medication
      Management Program in a community pharmacy setting. SETTING: Independent
      community pharmacy in an urban area. PRACTICE DESCRIPTION: Standard dispensing
      and consultative services and durable medical equipment supplies and services
      were offered in the pharmacy. Approximately 260 prescriptions were dispensed per
      10-hour workday. PRACTICE INNOVATION: Pharmacy workflow was redesigned with
      workstations in which each position was occupied at all times by pharmacy
      technicians or pharmacists. Clinical pharmacy interventions were delivered while
      normal dispensing processes continued. INTERVENTIONS: A Clinical Community
      Pharmacist provided education and counseling to patients newly diagnosed with
      diabetes as well as services to patients with other chronic diseases. RESULTS:
      During the first 6 months of the project, 221 clinical interventions were made;
      16 patients with diabetes (who had received 67 of the interventions) were
      enrolled in a medication management program. CONCLUSION: A Clinical Community
      Pharmacist in an urban setting can deliver clinical services during the normal
      dispensing process using an efficient workflow design.

PMID- 15991763
TI  - J. Leon Lascoff (1867-1943): champion of professionalism.

PMID- 15991764
TI  - Advisory Committee on Immunization Practices: working to improve vaccine use in
      the United States.

PMID- 15991765
TI  - New drugs: entecavir, ibandronate sodium, and pegaptanib sodium.

PMID- 15991766
TI  - OTC product: Sudafed PE.

PMID- 15991767
TI  - The short-term effects of air pollution on daily mortality in four Australian
      cities.
AB  - OBJECTIVE: To examine the short-term health effects of air pollution on daily
      mortality in four Australian cities (Brisbane, Melbourne, Perth and Sydney),
      where more than 50% of Australians reside. METHODS: The study used a similar
      protocol to APHEA2 (Air Pollution and Health: A European Approach) study and
      derived single-city and pooled estimates. RESULTS: The results derived from the
      different approaches for the 1996-99 period showed consistent results for
      different statistical models used. There were significant effects on total
      mortality, (RR = 1.0284 per 1 unit increase in nephelometry [10(-4).m(-1)], RR =
      1.0011 per 1ppb increase in NO2), and on respiratory mortality (RR = 1.0022 per
      1ppb increase in O3). No significant differences between cities were found, but
      the NO2 and particle effects may refer to the same impacts. Meta-analyses carried
      out for three cities yielded estimates for the increase in the daily total number
      of deaths of 0.2% (-0.8% to 1.2%) for a 10 microg/m3 increase in PM10
      concentration, and 0.9% (-0.7% to 2.5%) for a 10 microg/m3 increase in PM2.5
      concentration. CONCLUSIONS: Air pollutants in Australian cities have significant
      effects on mortality.

PMID- 15991768
TI  - The short-term effects of air pollution on hospital admissions in four Australian
      cities.
AB  - BACKGROUND: This paper examines the short-term health effects of air pollution on
      daily hospital admissions in Australian cities (those considered comprise more
      than 50% of the Australian population) for the period 1996-99. METHODS: The study
      used a similar protocol to overseas studies and derived single city and pooled
      estimates using different statistical approaches to assess the accuracy of the
      results. RESULTS: There was little difference between the results derived from
      the different statistical approaches for cardiovascular admissions, while in
      those for respiratory admissions there were differences. For three of the four
      cities (for the other the results were positive but not significant), fine
      particles (measured by nephelometry - bsp) and nitrogen dioxide (NO2) have a
      significant impact on cardiovascular admissions (for total cardiac admissions, RR
      = 1.0856 for a one-unit increase in bsp (10(-4) x m(-1)), RR = 1.0023 for a 1 ppb
      increase in NO2). For three of the four cities (for the other, the results were
      negative and significant), fine particles, NO2 and ozone have a significant
      impact on respiratory admissions (for total elderly respiratory admissions, RR =
      1.0552 per 1 unit (10(-4) x m(-1)) increase in bsp, RR = 1.0027 per 1ppb increase
      in NO2, RR = 10014 per 1 ppb increase in ozone for elderly asthma and COPD
      admissions). In all analyses the particle and NO2 impacts appear to be related.
      CONCLUSIONS: Similar to overseas studies, air pollution has an impact on hospital
      admissions in Australian cities, but there can be significant differences between
      cities.

PMID- 15991769
TI  - The health effects of jobs: status, working conditions, or both?
AB  - BACKGROUND: This study investigates whether the association of job strain and
      insecurity with health differs by status. METHODS: A cross-sectional study of
      2,249 employed workers aged 40-44 years conducted in two regions in south-east
      Australia in 2000 used a self-completed questionnaire to collect data.
      Multivariate analyses were used to compare depression, anxiety, physical health
      and general practitioner (GP) visits over 12 months across categories of job
      strain and insecurity for three status groups (high, middle and low). RESULTS:
      High job strain and job insecurity were independently associated with poor mental
      health, poor physical health and visits to the GP for all status groups when
      adjusted for confounders. High job strain was associated with depression (OR =
      2.46, 95% CI 1.96-3.07), anxiety (OR = 2.56, 95% Cl 2.05-3.20), lower mean
      physical health scores (-1.11, 95% CI -1.98 - -0.23), and more visits to the GP
      (IRR = 1.20, 95% CI 1.05-1.37). High job insecurity also showed significant
      associations with depression (OR = 3.03, 95% Cl 2.03-4.53), anxiety (OR = 2.66,
      95% CI 1.81-3.91), and GP visits (IRR = 1.27, 95% CI 1.01-1.60). There were no
      significant differences by status in the associations of job strain and
      insecurity with outcomes. CONCLUSION: High-status workers were just as likely as
      low-status workers to be exposed to adverse work conditions and both status
      groups showed similar health effects. IMPLICATIONS: Exposure to insecure and high
      strain jobs is likely to rise as economies and labour markets respond to
      globalisation and political change. High status may not protect employees from
      either exposure or impact, thus widening the population health consequences of
      adverse work conditions.

PMID- 15991770
TI  - Mortality rates among nuclear industry workers at Lucas Heights Science and
      Technology Centre.
AB  - OBJECTIVES: To assess whether workers at Lucas Heights Science and Technology
      Centre (LHSTC) have different levels of mortality from the New South Wales (NSW)
      and Australian populations. METHODS: A retrospective cohort study was undertaken
      at LHSTC. Data on 7,076 workers employed between 1957-98 were abstracted from
      personnel, dosimetry, and medical files. Deaths registrations in the cohort were
      identified to 1998 through electronic linkage of records with NSW and national
      registers of cancer incidence and mortality. Two inception cohorts were defined
      as including 4,717 and 3,543 workers in employment between 1972-98 and 1980-98,
      to examine cancer mortality and all-cause mortality respectively. RESULTS: All
      cause mortality was 31% lower than the national rates; all-cancer mortality was
      19% below the NSW rate. Of 37 specific cancers and groups of cancers examined,
      statistically significant excesses relative to NSW rates were observed only for
      pleural cancer mortality (SMR = 21.11; 95% Cl 8.79-50.72). CONCLUSIONS: The
      observed increase in the risk of cancer of the pleura was probably due to
      unmeasured exposures, given the lack of an established association with radiation
      exposure and the strong link to asbestos exposure.

PMID- 15991771
TI  - Usual water-related behaviour and 'near-drowning' incidents in young adults.
AB  - OBJECTIVE: To describe usual water-related behaviour and 'near-drowning'
      incidents in a cohort of young New Zealand adults. METHOD: This was a cross
      sectional study based on data collected as part of the Dunedin Multidisciplinary
      Health and Development Study, which is the study of a cohort (n = 1,037) born
      between 1 April 1972 and 31 March 1973 in Dunedin, New Zealand. The data analysed
      were collected at age 21 (1993/94). Each study member was given a face-to-face
      interview using a structured questionnaire. RESULTS: Males reported a higher
      level of water confidence, exposure to risk behaviours, and exposure to unsafe
      locations, and more 'near-drowning' incidents, than the females, but protective
      behaviour did not differ. Males and females who were 'confident' in the water
      were more likely to be exposed to unsafe water locations, and water-confident
      males were more likely to drink alcohol before water activities, but not boating.
      A total of 169 'near-drowning' incidents were reported by 141 study members (63%
      males). 'Near-drowning' incidents were associated with unsafe swimming
      environments for males (p < 0.001) and boating within two hours of consuming
      alcohol for females (p = 0.002). CONCLUSIONS: This study described usual water
      related behaviour and has provided preliminary evidence of the factors associated
      with 'near-drowning' incidents among a high-risk age group. Larger case-control
      studies are required to further investigate risk factors for 'near-drowning'.
      IMPLICATIONS FOR PRACTITIONERS: Further investigation is required to determine
      the effectiveness of providing water skills acquisition in both safe and unsafe
      environments on 'near-drowning' experience.

PMID- 15991772
TI  - Infections after coronary artery bypass graft surgery in Victorian hospitals-
      VICNISS Hospital Acquired Infection Surveillance.
AB  - OBJECTIVE: To establish a surveillance program reporting surgical site infection
      rates after coronary artery bypass graft surgery (CABGS) in Victorian public
      hospitals. METHODS: The VICNISS Coordinating Centre was established in 2002 to
      implement and co-ordinate a standardised surveillance system for hospital
      acquired infections in acute care Victorian public hospitals. Using validated
      definitions and methodology from the Centers for Disease Control and Prevention's
      National Nosocomial Infection Surveillance (NNIS) program, data on risk-adjusted
      surgical site infection (SSI) rates were collected and submitted to the
      Coordinating Centre for collation and reporting. RESULTS: Six large Melbourne
      metropolitan hospitals contributed data for CABGS for the period 11 November 2002
      to 30 June 2004, comprising a total of 3,482 patient records. Of 3,398 complete
      records, the aggregate SSI rates per 100 procedures for NNIS risk category 1 and
      2 were 4.4 (95% Cl 3.7-5.3) and 6.0 (95% Cl 4.5-7.8) respectively. The deep
      sternal SSI rates were 0.6 (95% Cl 0.4-1.3) and 0.5 (95% Cl 0.5-2.4 for patients
      in risk category 1 and 2 respectively. The most common pathogen identified was
      Staphylococcus aureus. CONCLUSION: This early data from VICNISS demonstrates
      similar CABGS SSI rates to those reported by NNIS in the USA, but higher than
      reported by the German Nosocomial Infection Surveillance System. IMPLICATIONS:
      The adoption of a statewide, co-ordinated surveillance program using validated
      internationally accepted methodologies allows hospitals to benchmark their
      infection rates against aggregate local and international data and to examine
      infection prevention interventions.

PMID- 15991773
TI  - Nowhere near the point of diminishing returns: correlations between chlamydia
      testing and notification rates in New South Wales.
AB  - OBJECTIVE: To examine the relationship between chlamydia testing and chlamydia
      detection rates in New South Wales, Australia, from 1999 to 2001. METHODS:
      Correlations between population-based chlamydia testing and notification rates-
      stratified by age group, area of residence, and year--were determined by linear
      regression. RESULTS: Strong positive correlations between chlamydia testing and
      notification rates were observed for both women (r = 0.91, p < 0.001) and men (r
      = 0.94, p < 0.001). Between 1999 and 2001, the chlamydia test positivity rate
      increased from 4.3% to 7.3% for women (p < 0.0001) and from 7.8% to 10.5% for men
      (p < 0.0001). CONCLUSIONS AND IMPLICATIONS: This study suggests that Australia
      could benefit from a major chlamydia screening program.

PMID- 15991774
TI  - Young people's use of condoms and their perceived vulnerability to sexually
      transmitted infections.
AB  - OBJECTIVE: Although sexually transmitted infections (STIs) are most prevalent
      among young people, they do not use condoms consistently to prevent infection.
      This study examined young people's perceptions of vulnerability to STIs and
      pregnancy. METHOD: A cross-sectional survey on sexual behaviour was carried out
      on a stratified random sample of school-going Year 12 and Year 13 young people
      aged 16-18 years in Christchurch, New Zealand. RESULTS: 1,136 students
      participated in the study, half of whom were sexually active. Fewer than half of
      the sexually active participants (44.6%) used condoms on every occasion of sexual
      intercourse. Only 23% of participants reported that they felt vulnerable to
      acquiring an STI, with a quarter of respondents reporting not using condoms
      because they did not think that either they or their partner had an infection,
      and a quarter reported not using condoms because they used other contraceptive
      measures. CONCLUSIONS: The results of this study support the premise that young
      people are more concerned about preventing unwanted pregnancy than STIs. Their
      perception of low risk of acquiring STIs is not without substance, however, as it
      was established that there was a low prevalence of Chlamydia trachomatis among
      this school-going population. The key to achieving more consistent condom use for
      STI prevention for young people may be through finding ways to get them to accept
      that they are vulnerable to STIs, despite the low prevalence among their peers,
      because the consequences of infection are far-reaching.

PMID- 15991775
TI  - Pilot of a novel cervical screening intervention: interactive voice response.
AB  - OBJECTIVE: This paper describes the pilot of an interactive voice response (IVR)
      cervical screening brief advice interface. METHOD: In September 2000, 5,000
      households within Cessnock, New South Wales, were contacted by an IVR system. The
      system randomly selected eligible women aged 18-69, assessed their cervical
      screening status and provided a tailored message about cervical screening. A
      computer-assisted telephone interview (CATI) evaluated intervention
      acceptability. Participation rates, participant demographics, IVR use by women,
      and IVR costs were also examined. RESULTS: 549 (12%) women listened to the IVR
      call and 587 (59%) completed the CATI interview. IVR listeners under-represented
      younger and older women, and over-represented women who were married, and of
      Aboriginal descent. The majority of women (98%) found IVR easy to answer and 90%
      agreed IVR reminders were a good idea. Unscreened and older women used the system
      more than screened or younger women. CONCLUSIONS: The IVR call was successfully
      used by a large number of women to obtain information on cervical cancer
      screening, with higher use by recognised risk groups. IMPLICATIONS: These results
      suggest that an IVR reminder might be useful to increase cervical screening rates
      since those most at risk also used IVR the most. The potential for linking IVR to
      a database to issue reminders in the same manner as Pap Test Register postal
      reminders needs to be explored.

PMID- 15991776
TI  - The mental health status of young adult and mid-life non-heterosexual Australian
      women.
AB  - OBJECTIVES: To compare the mental health status of early adult and mid-life
      Australian women according to sexual orientation. METHODS AND SAMPLE: Cross
      sectional analyses of the Australian Longitudinal Study on Women's Health (ALSWH)
      surveys for the younger (22-27 years) and mid-age (50-55 years) cohorts. Women
      were classified into one of four groups: exclusively heterosexual, mainly
      heterosexual, bisexual and lesbian. Regression analyses were used to examine the
      effects of sexual orientation on mental health after adjusting for age, region of
      residence and education and to assess the potential mediating roles of stress,
      abuse and social support. RESULTS: Younger, mainly heterosexual, bisexual and
      lesbian women had poorer mental health outcomes than exclusively heterosexual
      women on all outcome measures except anxiety in lesbian women, even after
      adjustment for age, region and education. Mid-age mainly heterosexual women had
      poorer mental health on all outcomes except for medically diagnosed anxiety and
      bisexual women had significantly higher odds of self-harm than exclusively
      heterosexual women. All non-heterosexual women in both cohorts reported higher
      levels of stress and lifetime abuse. Controlling for stress, abuse and social
      support attenuated the mental health findings. CONCLUSIONS: The poorer mental
      health in young non-heterosexual women and mid-life mainly heterosexual women
      highlights the need for health care providers to be particularly sensitive to
      mental health issues in these women. Stress, social support and lifetime abuse
      may play a role in explaining the poorer mental health and discrimination may
      also be important.

PMID- 15991777
TI  - Increase in saliva cotinine after three hours' exposure to second-hand smoke in
      bars.
AB  - OBJECTIVE: To determine whether measurement of cotinine in saliva is a sensitive
      measure of exposure to second-hand smoke (SHS) among customers in bars. DESIGN:
      Before/after comparison of saliva cotinine and subjective assessments of SHS.
      SETTING: Three bars in Wellington, New Zealand, June 2003. PARTICIPANTS: Eleven
      non-smoking medical students spent three hours in each location. They provided
      saliva samples before and after the visit, counted numbers of lit cigarettes in
      each bar, and assessed the smokiness of the venue. Samples were tested for
      cotinine using liquid chromatography coupled with mass spectrometry. RESULTS:
      Cotinine levels post-visit were consistently higher than baseline. The mean
      difference was 1.03 ng/mL with a 95% confidence interval of 0.76-1.30 ng/ mL.
      Adjustments to post-visit levels for metabolism and clearance of cotinine made
      very little difference to these results. Males tended to have higher baseline
      levels than females, and to show smaller increases. The bar with the greatest
      increase in cotinine was judged to be the smokiest on the basis of averaged
      cigarette counts and scores for presence of smoke and odour. CONCLUSION: The
      cotinine in saliva, when tested with the analytic methods described here,
      provides a means of assessing relatively short-term exposures to SHS.

PMID- 15991778
TI  - Regulation of environmental tobacco smoke by Australian drug treatment agencies.
AB  - OBJECTIVE: To determine how smoking is regulated in alcohol and other drug
      treatment agencies. METHOD: Australian drug treatment agencies were mailed
      questionnaires for completion by the manager and one other staff member (553
      packages posted). RESULTS: Questionnaires were returned by 260 (59.8%) eligible
      agencies. Most respondents (82.5% managers, 76.7% other staff) indicated their
      agency had a written policy regulating smoking. The vast majority (88.2%
      managers, 82.3% other staff) reported smoking was banned inside their agency,
      with the highest proportion of bans being in the area health category (95.8%
      managers, 93.7% other staff) and the lowest in the residential rehabilitation
      category (75.6% managers, 62.8% other staff). Of the respondents reporting a ban,
      19.1% of managers and 27.5% of other staff reported their agency's ban was not
      'always' enforced. Paired analyses suggested that other staff were more likely to
      indicate that the agency had no written policy or be unsure and managers were
      more likely to report that smoking bans were 'always' stringently enforced.
      Overall, a substantial minority of respondents (managers 28.6%, other staff
      40.2%) indicated that smoking occurred inside their agency at least occasionally.
      CONCLUSIONS AND IMPLICATIONS: A substantial proportion of Australian drug and
      alcohol agencies continue to permit smoking inside their premises. Policy
      initiatives and educational campaigns are required to promote the expansion of
      smoke-free conditions in this sector. Serious consideration should be given to
      making the adoption and enforcement of internal smoke-free policies a condition
      of any continued government funding.

PMID- 15991779
TI  - Could mainstream anti-smoking programs increase inequalities in tobacco use? New
      Zealand data from 1981-96.
AB  - OBJECTIVE: To examine changes in the socio-economic and ethnic distribution of
      smoking in the New Zealand population from 1981 to 1996, and to consider the
      implication of these data for policies aimed at reducing tobacco consumption.
      METHODS: Cross-sectional data were taken from 4.7 million respondents to the 1981
      and 1996 New Zealand Censuses and 4,619 participants in a 1989 national survey,
      aged 15 to 79 years. Smoking prevalence rates were calculated by socio-economic
      position and ethnicity. RESULTS: Smoking prevalence fell in the period 1981-96 in
      every population group. However, socio-economic and ethnic differences in smoking
      increased in relative terms. Smoking prevalence ratios comparing the least
      advantaged with the most advantaged groups increased in men from 1.20 to 1.53 by
      income, 1.54 to 1.85 by education, and 1.49 to 1.67 by ethnicity. In women,
      prevalence ratios increased from 1.17 to 1.51 by income, 1.55 to 2.02 by
      education, and 1.85 to 2.20 by ethnicity. The greatest increase in socio-economic
      differences may have occurred during the 1980s, the period of greatest overall
      decline in total population smoking. CONCLUSIONS: Socio-economic and ethnic
      disparities in New Zealanders' smoking patterns increased during the 1980s and
      '90s, a period of significant decline in overall smoking prevalence.
      IMPLICATIONS: Public health programs aimed at reducing tobacco use should pay
      particular attention to disadvantaged, Indigenous and ethnic minority groups in
      order to avoid widening relative inequalities in smoking and smoking-related
      health outcomes.

PMID- 15991781
TI  - New Zealand's response to arboviruses and exotic mosquitoes.

PMID- 15991780
TI  - A randomised controlled trial to evaluate the efficacy of a nurse-provided
      intervention for hospitalised smokers.
AB  - OBJECTIVE: Does the provision of a nurse-based intervention lead to smoking
      cessation in hospital patients? METHODS: At tertiary teaching hospital in
      Newcastle, Australia, 4,779 eligible (aged 18-80, admitted for at least 24 hours,
      and able to provide informed consent) and consenting (73.4%) in-patients were
      recruited into a larger cross-sectional survey. 1,422 (29.7%) smokers (in the
      last 12 months) were randomly assigned to control (n = 711) or intervention group
      (n = 711). The brief nurse-delivered intervention incorporated: tailored
      information, assessment of withdrawal, offer of nicotine replacement therapy,
      booklets, and a discharge letter. Self-reported cessation at 12 months was
      validated with CO and salivary cotinine. RESULTS: There were no significant
      differences between groups in self-reported abstinence at three or 12 months post
      intervention, based on an intention to treat analysis. At three months, self
      reported abstinence was 27.3% (I) and 27.5% (C); at 12 months was 18.5% (I) and
      20.6% (C). There were no differences in validation of self-report between
      intervention and control groups at 12 months. CONCLUSION: This brief nurse
      provided in-patient intervention did not significantly increase the smoking
      cessation rates compared with the control group at either three or 12-month
      follow-up. IMPLICATIONS: A systematic total quality improvement model of
      accountable outcome-focused treatment, incorporating assertive physician-led
      pharmacotherapy, routine assessment and recording of nicotine dependence (ICD 10
      coding), in- and outpatient services and engagement from multidisciplinary teams
      of health professionals may be required to improve treatment modalities for this
      chronic addictive disorder.

PMID- 15991782
TI  - [Conservative treatment of open incomplete radial fracture in an adult horse].
AB  - A non-displaced radialfracture of a horse was,diagnosed. The horse had an open
      fracture resulting from external trauma. A diagnosis was made on radiographs
      taken 48h after trauma. The horse was treated conservatively by box rest and
      Robert-Jones bandages. After 7 days the wound was opened to let the wound
      drainage necrotic material and small sequesters and was washed every other day.
      After 7 weeks, radiographs showed complete consolidation. Four months after the
      injury the horse was back to work at his former level and is still working two
      years after the incident.

PMID- 15991783
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Slaughter mask].

PMID- 15991784
TI  - [Overdose veterinary medicine].

PMID- 15991785
TI  - [PDA (Personal Digital Assistant) in the veterinary practice?].

PMID- 15991786
TI  - Two sides of the coin on respiratory viruses.

PMID- 15991787
TI  - Digging its way in: lab digital imaging.

PMID- 15991788
TI  - For HIV genotyping, plenty of growing pains.

PMID- 15991789
TI  - Clinical pathology.

PMID- 15991790
TI  - Cytology PT.

PMID- 15991791
TI  - Low wages, high risk.

PMID- 15991792
TI  - Let's learn from each other about CP pay.

PMID- 15991793
TI  - Glucose testing variability and the need for an expert oversight committee.

PMID- 15991794
TI  - Linking software making gains and foraying into new domains.

PMID- 15991795
TI  - Rapid transit--geting data to public health agencies.

PMID- 15991796
TI  - Proficiency testing finds too-high cutoffs.

PMID- 15991797
TI  - Clinical and laboratory evaluation of a new specific ELISA for intact proinsulin.
AB  - Intact proinsulin is a marker for pancreatic beta-islet cell secretion status,
      and elevated levels indicate insulin resistance of type 2 diabetic patients with
      a high diagnostic specificity. Determination of intact proinsulin in fasting
      morning plasma samples can be used to establish and/or identify the optimal anti
      diabetic treatment as well as to monitor a potential protective treatment effect
      on beta-islet cell dysfunction. For widespread use as a routine marker, simple
      and reliable assays must become available for measurement in clinical
      laboratories. This study was performed to evaluate a new ELISA method specific
      for intact proinsulin determination compared with a commercial chemiluminescence
      test. Intra-assay imprecision was determined to be 2.4 - 5.5% (inter-assay: 3.2 -
      4.3%). A sample cohort derived from non-diabetic healthy subjects (66 female, 29
      male, age (median, range): 37 (19-77) years) was used to calculate a reference
      range for non-diabetic individuals of 1.8 - 11.0 pmol/l. The comparison of
      samples obtained from 7 diabetic patients (2 female, 5 male, age: 66 (44-72)
      years) from oral glucose tolerance tests resulted in an excellent correlation
      between the ELISA and the chemiluminescence assay (r = 0.989; p<0.001). A sample
      stability investigation with different sample specimens revealed that intact
      proinsulin is stable for two days at room temperature in EDTA whole blood and
      heparin whole blood tubes without centrifugation, while serum samples should be
      centrifuged immediately and frozen to retain intact proinsulin concentrations. As
      EDTA whole blood is the routine sample specimen for determination of HbA1c, a
      marker frequently measured in diabetic patients, this finding underlines the
      practicability of analyzing intact proinsulin from the same blood specimen. In
      conclusion our study revealed that the new ELISA shows excellent agreement with
      the commonly used chemiluminescence immunoassay. The ELISA can easily be
      introduced into routine laboratories and does not require any further specific
      instrumentation. Our additional finding that intact proinsulin is stable in EDTA
      whole blood samples, which can be obtained from the routine.sample for HbA1c
      measurement, is increasing the probability of the acceptance of this marker for
      routine assessment of beta-cell dysfunction and insulin resistance in type 2
      diabetes.

PMID- 15991798
TI  - Evaluation of the ARCHITECT STAT troponin-I assay.
AB  - We evaluated the immunoassay for troponin I (TnI) which is now available on the
      integrated ARCHITECT analyzer ci8200 from Abbott. Coefficients of variation (CV)
      for between-day imprecision were 5.6%, 4.7% and 5.1% at TnI levels of 0.13
      microg/l (mean of low control), 0.49 microg/l (medium control) and 11.2 microg/l
      (high control), respectively. All measurements of controls lay within pre
      specified concentration ranges. The functional sensitivity at an imprecision
      level of 10% was found to be 0.04 microg/l, while the 99th percentile of the
      reference range derived from 130 apparently healthy subjects was determined as
      0.02 microg/l with a corresponding CV of 15%. Thus, as none of the currently
      reported TnI tests the ARCHITECT STAT assay does not meet exactly the ESC/ACC
      consensus criteria for troponin testing but seems to perform better than many of
      the tests currently used in practice.

PMID- 15991799
TI  - Mutations in the transketolase-like gene TKTL1: clinical implications for
      neurodegenerative diseases, diabetes and cancer.
AB  - Transketolase proteins or transketolase enzyme activities have been related to
      neurodegenerative diseases, diabetes, and cancer. Transketolase enzyme variants
      and reduced transketolase enzyme activities are present in patients with the
      neurodegenerative disease Wernicke-Korsakoff syndrome. In Alzheimer's disease
      patients transketolase protein variants with different isoelectric points or a
      proteolytic cleavage leading to small transketolase protein isoforms have been
      identified. In diabetes mellitus patients reduced transketolase enzyme activities
      have been detected and the lipid-soluble thiamine derivative benfotiamine
      activates transketolase enzyme reactions, thereby blocking three major pathways
      of hyperglycemic damage and preventing diabetic retinopathy. In cancer inhibition
      of transketolase enzyme reactions suppresses tumor growth and metastasis. All the
      observed phenomena have been interpreted solely on the basis of a single
      transketolase gene (TKT) encoding a single transketolase enzyme. No mutations
      have been identified so far in TKT transketolase explaining the altered
      transketolase proteins or transketolase enzyme activities found in
      neurodegenerative diseases, diabetes and cancer. We demonstrate the presence of a
      second transketolase enzyme (TKTL1) in humans. During the evolution of the
      vertebrate genome, mutations in this transketolase gene (TKTL1) have led to
      tissue-specific transcripts different in size, which encode an enzymatically
      active transketolase protein as well as different smaller protein isoforms. The
      mutations within the TKTL1 gene caused a mutant transketolase enzyme with an
      altered substrate specificity and reaction modus. Here we characterize the TKTL1
      gene and its encoded TKTL1 protein(s) and discuss the medical and clinical
      implications of this mutated transketolase. We furthermore postulate a novel
      metabolic concept for the understanding, prevention and therapy of
      neurodegenerative diseases, diabetes and cancer.

PMID- 15991800
TI  - Better stability of total homocysteine measurement with sodium fluoride than with
      EDTA.
AB  - The total homocysteine (tHcy) plasma concentration increases 10% per hour when
      whole blood is collected on ethylene diamine tetraacetate (EDTA) and stored at
      room temperature. The aim of this study was to investigate the stability of tHcy
      plasma concentration during 24 hours of storage at room temperature in two
      different collection tubes: EDTA and sodium fluoride (NaF). The evolution of tHcy
      plasma concentration was also compared in two different populations: healthy
      individuals (controls) and patients with end-stage renal failure, known to have
      increased plasma tHcy concentrations. Plasma was separated from erythrocytes at
      0, 2, 6 and 24 hours. tHcy was measured with a competitive immunoassay on
      Immulite 2000 (Diagnostic Products Corporation). Plasma tHcy concentration
      started to rise significantly on EDTA after two hours of storage in patients and
      controls in comparison to baseline (defined as time: 0 hour). It remained stable
      on NaF during the first two hours and started to rise significantly after six
      hours of storage for both populations. In conclusion, NaF tubes should be
      preferred to EDTA tubes for tHcy determination in routine clinical chemistry
      laboratories.

PMID- 15991801
TI  - Anti-oxLDL antibodies--marker for arterial thromboses in antiphospholipid
      syndrome?
AB  - Antibodies against oxidized low-density lipoproteins (anti-oxLDL antibodies) are
      involved in the development of atherosclerosis in animal models, but their role
      in humans is not clear. The aim of this study was to explore the relationship
      between the presence of anti-oxLDL antibodies and the presence of anti
      beta2glycoprotein I (beta2gpI) antibodies, anticardiolipin antibodies and lupus
      anticoagulant. We also analyzed the relationship between the appearance of anti
      oxLDL antibodies and clinical signs of antiphospholipid syndrome. This study
      included three groups of patients: 27 patients with primary antiphospholipid
      syndrome, 20 with secondary antiphospholipid syndrome associated with systemic
      lupus erythematosus and 13 patients with systemic lupus erythematosus. Levels of
      anti-oxLDL, anticardiolipin and anti-beta2gpI antibodies were detected by ELISA.
      The presence of lupus anticoagulant was detected by coagulation tests. We found
      that the presence of anti-oxLDL antibodies was associated with a history of
      arterial thromboses in patients with secondary antiphospholipid syndrome (chi2 =
      8.89, p < 0.01) and in patients with primary antiphospholipid syndrome (chi2 =
      4.64, p < 0.05). Also, the appearance of anti-oxLDL antibodies was associated
      with the presence of anti-beta2gpI antibodies (chi2 = 4.25, p < 0.05), which was
      not dependent on diagnosis. These preliminary observations have to be confirmed
      in a larger study.

PMID- 15991802
TI  - Immunonephelometric determination of fibrinogen on citrated or heparinized
      plasma: comparison with functional Clauss method.
AB  - BACKGROUND: Fibrinogen is routinely determined by functional assay on citrated
      plasma in the hematology department. However, immunoassay can be performed easily
      with nephelometric analyzer in the clinical chemistry laboratory allowing
      automatization. The aim of this study was first to compare the clotting von
      Clauss method (activity assay) with an immunonephelometric method (antigen assay)
      on the BN ProSpec (Dade Behring). Moreover, we evaluated the possibility of
      collecting blood samples on heparin to facilitate blood collection for clinicians
      and reduce required blood collection volumes for dosages. METHODS: In a first
      step of experiment, the accuracy of immunonephelometric analytical performance
      was tested on heparinized and citrated tubes. For comparison studies, fibrinogen
      activity was then determined on citrated tubes in the hematology department and
      antigen measurement was performed on both citrated and heparinized plasma from
      130 consecutive patients. RESULTS: As a result, the immunonephelometric method
      shows reliable performance and clinical sample measurements are not affected by
      the method used, validating the use of heparinized plasma samples for fibrinogen
      antigen determination with Dade Behring reagents.

PMID- 15991803
TI  - Fatty acid oxidation defects as a cause of neuromyopathic disease in infants and
      adults.
AB  - Fatty acids are a major fuel for the body and fatty acid oxidation is
      particularly important during fasting, sustained aerobic exercise & stress. The
      myocardium and resting skeletal muscle utilise long-chain fatty acids as a major
      source of energy. Inherited disorders of fatty acid oxidation seriously
      compromise the function of muscle and other highly energy-dependent tissues such
      as brain, nerve, heart, kidney & liver. Defects of fatty acid oxidation lead to a
      range of neuromyopathic disease in both adults and children. Such defects
      encompass a wide spectrum of clinical disease, presenting in the neonatal period
      or infancy with recurrent hypoketotic hypoglycaemic encephalopathy, liver
      dysfunction and hyperammonaemia with neurosensory deficits secondary to the acute
      onset. In addition, there may be cardiac arrhythmias and/or progressive
      cardiomyopathy, which may give rise to secondary hypoxic-ischaemic
      encephalopathy. In older children, adolescence or adults there is often exercise
      intolerance with episodic myalgia or rhabdomyolysis in association with prolonged
      aerobic exercise or other exacerbating factors. Some disorders are particularly
      associated with toxic metabolites that may contribute to encephalopathy,
      polyneuropathy, axonopathy and pigmentary retinopathy. Diagnosis is through
      clinical suspicion with appropriate investigations in blood and urine taken
      during crisis. Definitive diagnosis is usually by fibroblast assay. Treatment is
      generally through avoidance of fasting, frequent carbohydrate rich feeds and in
      long-chain defects MCT supplementation. Novel treatments include the use of D,L-3
      hydroxybutyrate and the potential use of fibrates to increase mutant protein
      levels in mild disorders.

PMID- 15991804
TI  - No magic bullet.

PMID- 15991813
TI  - What is the most unusual thing you've done to protect patient?

PMID- 15991815
TI  - Treating HTN crisis. How low? How fast?

PMID- 15991816
TI  - The power of low-tech nursing.

PMID- 15991817
TI  - Summer injuries: heat emergencies.

PMID- 15991818
TI  - Patient information. Preventing heat emergencies.

PMID- 15991819
TI  - What's wrong with this patient?

PMID- 15991820
TI  - Bariatric surgery. It's no easy fix.

PMID- 15991821
TI  - Solving the child care dilemma.

PMID- 15991822
TI  - Is this any way to evaluate performance?

PMID- 15991823
TI  - Vectorial role of some dermanyssoid mites (Acari, Mesostigmata, Dermanyssoidea).
AB  - Among transmissible diseases, vectorial diseases represent a major problem for
      public health. In the group of acarina, while ticks are the most commonly
      implicated vectors, other arthropods and notably Dermanyssoidea are also involved
      in the transmission of pathogenic agents. Since the role of this superfamily is
      at present largely unknown, we have reviewed the vectorial role of these mites in
      the appearance, survival and propagation of pathogens. Various authors have shown
      that Dermanyssoidea are implicated in the transmission of both bacteria
      (Salmonella, Spirocheta, Rickettsia or Pasteurella) and viruses (equine
      encephalitis viruses, West Nile virus, Fowl pox virus, the virus causing
      Newcastle disease and tick borne encephalitis viruses or hantaviruses). Finally,
      some authors have also shown their role in the transmission of some protozoa and
      filaria. As the vectorial character of such mites has been more clearly
      demonstrated (Dermanyssus gallinae, Omithonyssus bacoti and Allodermanyssus
      sanguineus), it would be interesting to continue studies to better understand the
      role of this superfamily in the epidemiology of certain zoonoses.

PMID- 15991824
TI  - [Bird fleas (Insecta: Siphonaptera): taxonomic diversity, biogeographical
      distribution].
AB  - If Mammals are the primary hosts of Siphonaptera, 6% of them have changed their
      trophic appetency for Birds. What are the reasons, what are the adaptations to be
      adopted by Fleas, what are the families or species groups of fleas concerned, and
      at last what are the host-families? As to this last question, it is clear that
      deviation was ecological but not phyletical.

PMID- 15991825
TI  - Molecular characterization of Tunga trimamillata and T. penetrans (Insecta,
      Siphonaptera, Tungidae): taxonomy and genetic variability.
AB  - A new species of the genus Tungo, T. trimamillata has recently been described on
      the basis of several morphological traits. To explore the taxonomic status of
      this flea with respect to T. penetrans, we undertook a molecular analysis of
      cytochrome oxydase II and 16S rDNA mitochondrial genes and of the internal
      transcribed spacer 2 nuclear marker on samples of both species. Maximum Parsimony
      evaluations of the three data set indicate a differentiation compatible with a
      specific rank between the two fleas with very high levels of divergence. Both
      mitochondrial and nuclear data are in line with a recent bottleneck in the
      Malagasy population of T. penetrans, possibly due to the recent colonisation of
      Africa via human transportation. Further, significantly lower mitochondrial
      variability in the Ecuadorian populations of T. penetrans with respect to the T.
      trimamillata ones is also evidenced.

PMID- 15991826
TI  - Eimeria (Coccidia: Eimeridea) of hares in France: description of new taxa.
AB  - The oocysts of coccidian of the genus Eimeria were sought in the caecal contents
      of 46 Lepus granatensis and 18 L. europaeus captured in France. Parasites were
      found in 34 of the hares. Parasite load was mainly very low. However, species
      diversity was considerable. 21 species or subspecies were identified, of which 13
      species and two subspecies were not previously described. Three of the taxa, E.
      robertsoni, E. semisculpta and E. townsendi, previously identified on numerous
      occasions in western Europe and, corresponding to forms or variants created
      before 1960 that have been subsequently elevated to a specific level, appear to
      be invalid. Indeed, the parasite descriptions from the material used to effect
      this modification do not correspond to the original descriptions. A stable
      equilibrium, as generally observed in the case of many congeneric species co
      infection of the same host, was not observed in the hares. This has been
      attributed to the solitary habits of the host and of the probable polyphyletic
      nature of the genus Eimeria. Paleontological data for the Leporidae indicate that
      rabbit parasites are derived from those of the hare.

PMID- 15991827
TI  - Graphidioides subterraneus n. sp. (Nematoda: Trichostrongyloidea) from the South
      American subterranean rodent Ctenomys talarum Thomas, 1898 (Rodentia:
      Octodontidae).
AB  - A new nematode species, Graphidioides subterraneus n. sp., found in the stomach
      of C. talarum from Argentina is described. The new species more closely resembles
      G. mazzai Lent & Freitas, 1935, parasite of Galea leucoblephara from Argentina,
      and G. kravetzi Sutton & Durette-Desset, 1995, parasite of Holochilus
      brasiliensis from Uruguay. It can be distinguished by shorter spicules, by the
      shape of the gubernaculum, by shorter uterine branches, and by a different number
      of ridges of the synlophe all along the body.

PMID- 15991828
TI  - A stage-specific open reading frame from three-day old adult worms of Trichinella
      spiralis encodes zinc-finger motifs.
AB  - The aim of the study was to isolate genes coding for stage-specific antigens of
      T. spiralis. Such antigens may then be associated with local and systemic immune
      responses against adult T. spiralis. Recombinant clones were obtained with an
      adult stage specific probe from a cDNA library of three-day old adult T.
      spiralis. Several cDNA clones encoding the same peptide were identified and their
      stage specificity was confirmed by northern blot analysis. Three independent
      clones were fully sequenced, and the resulting sequence found to code for a 487
      amino acid peptide with a deduced molecular weight of approximately 55 kDa.
      Sequence analysis showed that the 55 kDa peptide contained putative DNA binding
      motifs, suggesting that this protein may be involved in transcriptional
      regulation during the early development of the parasite.

PMID- 15991829
TI  - Strain characterization of Echinococcus granulosus protoscoleces of cattle origin
      using the in vitro vesicular development.
AB  - The aim of this work was to characterize the strain of protoscoleces of E.
      granulosus of cattle origin using the in vitro vesicular development. The in
      vitro development of these samples was compared to samples of sheep origin
      determined previously by genetic analyses as common sheep strain (G1). There were
      similarities between sheep and cattle samples not only in the time of microcysts
      formation, but also in the development process. Vesiculated protoscoleces and
      protoscoleces with posterior bladders appeared during the first week of
      incubation. After 14 days of culture, a laminated layer appeared like a fine
      membrane in one of the extremes of the protoscoleces. In the sheep samples,
      microcysts were observed between 19 and 20 days. In the cattle samples,
      microcysts appeared between 20 and 23 days. The coincidence between the
      development times and physiological characteristics found in the present study
      may indicate that the parasites from cattle and sheep were of the same strain.

PMID- 15991830
TI  - Dientamoeba fragilis is more prevalent than Giardia duodenalis in children and
      adults attending a day care centre in Central Italy.
AB  - Giardia duodenalis is a well recognised enteropathogen, while Dientamoeba
      fragilis is rarely detected and consequently it is not recognised as an important
      human pathogen. In 2002-2003, a survey has been carried out on enteroparasites in
      faecal samples of outpatients attending a day care centre in the town of Perugia
      (Central Italy). To improve the detection level, at least three samples from each
      patient were collected at different days and within two hours from defecation.
      The coproparasitological examination has been carried out by direct microscopic
      examination, faecal concentration, and Giemsa and modified Ziehl-Nielsen
      stainings of faecal smears. The genotypes of Giardia duodenalis isolates were
      determined by PCR of the beta-giardin gene. Of 1,989 enrolled people (966
      children, 1,023 adults), 165 persons (8.3%; 153 adults, 15.0%; 12 children,
      1.2%), were positive for parasites, but only 1 12 adults (73.2% of those
      infected) and eight children (66.7% of those infected) harboured D. fragilis and
      G. duodenalis. Both the Assemblages A and B were detected in 18 G. duodenalis
      isolates examined at the beta-giardin gene. The higher prevalence of D. fragilis
      infections than that of G. duodenalis is probably related to the method used, a
      procedure, which is rarely followed in laboratories for the diagnosis of enteric
      parasites. These epidemiological data suggest that when faecal samples are
      examined after a period of time and without Giemsa staining, most D. fragilis
      infections goes undetected.

PMID- 15991831
TI  - Efficacy of atovaquone and sulfadiazine in the treatment of mice infected with
      Toxoplasma gondii strains isolated in Brazil.
AB  - The efficacy of atovaquone and sulfadiazine was examined alone or in combination
      for the treatment of mice infected with six Brazilian Toxoplasma gondii strains
      previously genotyped using the PCR-RFLP assays of the SAG2 gene, in addition to
      RH strain. Swiss mice were infected intraperitoneally with 10(2) tachyzoites from
      each strain of T. gondii and treated with 6.25, 12.5, 25 and 50 mg/Kg/day of
      atovaquone or 40, 80, 160 and 320 mg/Kg/day of sulfadiazine. In a second
      experiment, mice were treated with the association of previously determined doses
      of each drug. Treatment started 48 hours post-infection, and lasted 10 days. The
      susceptibility of T. gondii to atovaquone and to sulfadiazine was different
      according to the parasite strain. It was observed strains that are susceptible to
      atovaquone, and strains that are resistant to it. Type I strains were more
      susceptible to the activity of sulfadiazine and more resistant to atovaquone. Yet
      type III strains were susceptible to atovaquone and to sulfadiazine. Association
      of atovaquone and sulfadiazine presented a synergic effect in the treatment of
      mice infected with RH type I strain and an additive effect in the treatment of
      mice infected with one type I strain and with two type III strains.

PMID- 15991833
TI  - Equine infection with Leishmania in Portugal.
AB  - The present report describes the first case of equine leishmaniasis in Portugal.
      Leishmania infection was detected in one animal, which presented an ulcerated
      skin lesion. Diagnosis was based on serology by CIE, and parasite DNA detection
      by real-time PCR using a probe specific for L. infantum. This finding requests
      further leishmaniasis equine surveys in order to clarify the role of the horse as
      reservoir host in european endemic areas.

PMID- 15991832
TI  - Immunoblotting analysis of somatic components of Dirofilaria immitis.
AB  - SDS-PAGE analysis of Dirofilaria immitis extracts demonstrated the complexity of
      somatic protein component of adult male similar to that of adult female worm.
      Western blot analysis showed six major peptide bands of 85, 66, 42, 20, 16.2 and
      14.5 kDa recognized in the sera of infected dogs. Western blotting sera from dogs
      with Dirofilaria immitis infection suggest that antigenic components in the low
      molecular weight region may be related to the anti-parasitic mechanism of the
      host.

PMID- 15991834
TI  - Isradipine--a calcium channel blocker--does not potentiate chloroquine
      antiplasmodial activity against Plasmodium falciparum.
AB  - Culturing fresh clinical isolates of P. falciparum and using the isotopic method,
      we tested separately chloroquine and isradipine--a calcium channel blocker--, and
      also the combination isradipine plus chloroquine. Tested wild isolates were
      chloroquine-sensitive. With regard to the combination isradipine/chloroquine, the
      isobolograms obtained indicate that isradipine antagonises chloroquine
      antiplasmodial activity. Taking into account these findings, we discuss the
      issues related to the calcium channel blocker molecules.

PMID- 15991835
TI  - A trichinosis outbreak caused by wild boar meat in Turkey.

PMID- 15991836
TI  - CD34+ fibrocytes in normal mitral valves and myxomatous mitral valve
      degeneration.
AB  - We investigated a total of 15 mitral valves with myxomatous degeneration and
      compared these with normal mitral valves. In normal mitral valves, stromal cells
      located in the fibrosa and spongiosa showed small bipolar cytoplasmic processes
      and were found to be positive for CD34, suggesting a close relationship to CD34+
      fibrocytes. In cases of myxomatous degeneration, stromal cells showed an altered
      morphology in that they exhibited multipolar cytoplasmic processes, appeared to
      be hyperplastic, and were increased in number. This study is the first to report
      on CD34+ fibrocytes making up the majority of mitral valve stromal cells. Major
      factors in the development of myxomatous valve degeneration are MMP-9, as well as
      collagen I and III, which have been reported to be secreted by CD34+ fibrocytes.
      Therefore, it is likely that CD34+ fibrocytes are involved in the pathogenesis of
      myxomatous mitral valve degeneration.

PMID- 15991837
TI  - Vascular changes in the periosteum of congenital pseudarthrosis of the tibia.
AB  - The etiology and the pathogenesis of congenital pseudarthrosis of the tibia (CPT)
      are still unknown. The affected tibia exhibits insufficient mechanical strength
      and osteogenetic capability. CPT is frequently associated with neurofibromatosis
      type 1 (NF1; von Recklinghausen's disease); however, both diseases have not yet
      been linked pathogenetically. This study presents the pathomorphologic findings
      of CPT under special consideration of NF1. Therefore, samples from patients
      operated on for CPT (n = 4) with (n = 3) and without (n = 1) neurofibromatosis
      were investigated by light microscopy, immunohistochemistry, and electron
      microscopy. The most striking finding in all patients was thickened periosteum
      with accumulation of nerval cells surrounding small arteries, causing subtotal or
      complete obliteration. In conclusion, impaired vascularization can result in
      decreased osteogenic capabilities. The similarity of ultrastructural findings in
      the abnormal periosteum and in skin neurofibromas of neurofibromatosis patients
      may indicate a pathogenetic association of both diseases.

PMID- 15991838
TI  - CD34 as a marker for evaluating angiogenesis in cervical cancer.
AB  - CD34 is an antigen present in hematopoietic progenitor cells and endothelial
      cells. Anti-CD34 antibody is a highly sensitive marker for endothelial cell
      differentiation and has also been studied as a marker for vascular tumors.
      However, there are few studies relating it to cervical carcinoma. The aim of this
      study was to evaluate the association between angiogenesis and the
      pathoanatomical features of cervical carcinoma using anti-CD34 monoclonal
      antibody. Sixty-two patients with invasive carcinoma of the uterine cervix in
      stages Ib-IIa were included. A primary monoclonal antibody specific for CD34
      (Anti-Human Hemapoietic Progenitor Cell, CD34 Class II, Clone QBEnd 10, Code
      M7165, DAKO Corporation) was used in a dilution of 1:25. Microvessel density
      varied from 4.8 to 20 and was higher in undifferentiated carcinomas (p = 0.03;
      Mann-Whitney test). Higher microvessel density was associated with squamous cell
      carcinoma, odds ratio (OR) 8.8 (95% CI: 1.0-76.1), while the presence of
      lymphatic invasion yielded an OR of 2.6 (95% CI: 0.9-7.4). This study suggested
      that anti-CD34 antibody reactivity in cervical carcinoma is associated with
      pathoanatomical features indicative of poorer prognosis.

PMID- 15991839
TI  - Mitochondria-rich normal, metaplastic, and neoplastic cells show overexpression
      of the epitope H recognized by the monoclonal antibody H.
AB  - The epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a
      specific conformation and/or environment recognized by monoclonal antibody H
      (mAbH). We have previously shown that the epitope H is present in more than one
      polypeptide and in various types of normal and pathological cells. In the present
      study, we focused on mitochondria-rich normal, metaplastic, and neoplastic cells,
      prompted by our recent immuno-electron microscopy findings that mAbH clearly
      stains the mitochondria of breast epithelial cells in infiltrating ductal breast
      carcinomas and fibroadenomas. The indirect immunoperoxidase method was applied
      using the mAbH to investigate the distribution of the epitope H in mitochondria
      rich normal cells and in metaplastic and neoplastic oncocytic cells.
      Immunohistochemical staining for the mAbH was observed in oxyphil cells of
      parathyroid glands, in striated duct cells of parotid glands, in urinary tubules
      of kidneys, in parietal cells of gastric body mucosa, in oxyphil cells of
      Hashimoto's thyroiditis, in epithelial cells of Warthin's tumors of the parotid
      gland, in neoplastic cells of oxyphil adenomas and carcinomas (Hurthle's tumors)
      of the thyroid gland, and in neoplastic cells of oncocytomas of the kidneys. The
      present study shows that the epitope H is strongly expressed in mitochondria-rich
      normal cells, as well as in metaplastic and neoplastic oncocytic cells, which are
      known to have cytoplasms packed with mitochondria. Since mAbH recognizes an O
      GlcNAc residue, our findings indicate that O-GlcNAc-glycosylated polypeptides are
      present at mitochondria where the components of the respiratory chain and energy
      transduction are localized. These findings may be of interest for gaining insight
      into the histophysiology of mitochondria-rich normal cells and into the
      pathogenesis of oncocytic lesions, since O-GlcNAc glycosylation may modify
      proteins involved in oncogenesis such as tumor suppressor proteins and
      oncoproteins, as well as proteins with important biological functions such as
      cytoskeletal proteins, transcription factors, heat-shock proteins, and chromatin
      proteins.

PMID- 15991840
TI  - Idiopathic multicentric Castleman's disease. A clinicopathologic and
      immunohistochemical study of five cases.
AB  - Several lymphoproliferative disorders may be interpreted as multicentric
      Castleman's disease (MCD) clinicopathologically. These include HIV infection,
      autoimmune-disease-associated lymphadenopathy, idiopathic plasmacytic
      lymphadenopathy with polyclonal hyperimmunoglobulinemia, "idiopathic MCD", POEMS
      syndrome (polyneuropathy, anasarca, organomegaly, endocrinopathy, M-proteins, and
      skin lesions), and non-Hodgkin's lymphomas. Among these, idiopathic MCD appears
      to be relatively rare. We report on the clinicopathologic and immunohistologic
      findings of five cases of idiopathic MCD and discuss the problems regarding their
      differential diagnosis. Some of the characteristic clinical findings of POEMS
      syndrome, including hepatosplenomegaly, skin change, endocrine abnormalities and
      anasarca, were present in all five cases. However, during the course of disease,
      minimal diagnostic criteria for POEMS syndrome, i.e., monoclonal plasma cell
      proliferation and sensory motor neuropathys, were absent in all five cases. The
      serum interleukin-6 level and the vascular endothelial growth factor level were
      found to be elevated in two of the cases examined. Various autoantibodies were
      detected in three cases. However, none of them fulfilled the diagnostic criteria
      for any of the definite autoimmune-disease. Histologically, three lesions
      exhibited a mixed type of Castleman's disease, and two exhibited the hyaline
      vascular type. The majority of the germinal centers were of the hyaline-vascular
      or epithelioid germinal type, with a few hyperplastic germinal centers. The
      interfollicular area was characterized by prominent vascularity. Moderate to
      large sheets of plasma cells were observed in three mixed type cases. The
      polytypic nature of B-lymphocytes was demonstrated by immunohistochemistry and
      polymerase chain reaction. Immunohistochemical study demonstrated that the
      majority of germinal centers exhibited a tight/concentric pattern of FDC network.
      Few CD57-positive T-cells were observed in the hyaline-vascular and epithelioid
      follicles. The lack of CD57-positive T-cells appears to be related to the
      formation of abnormal germinal centers in the MCD.

PMID- 15991841
TI  - Pleomorphic adenoma (benign mixed tumor) of the breast: a case report and review
      of the literature.
AB  - We report a case of pleomorphic adenoma (benign mixed tumor) of the breast, which
      is an extremely rare location for this tumor. Examination of a 55-year-old woman
      unexpectedly revealed a mass measuring 0.8 cm in diameter in the subareolar
      region of the right breast. Excisional biopsy was performed, and the tumor
      histologically showed pleomorphic adenoma composed of duct epithelial cells,
      myoepithelial cells, and a myxochondroid matrix. Immunohistochemically, duct
      epithelial cells were positive for the estrogen receptor, but negative for the
      progesterone receptor. The nuclei of the spindle and myoepithelial cells were
      immunoreactive for HMGI-C and HMGI(Y) proteins, indicating a histogenesis similar
      to pleomorphic adenoma of the salivary glands. Interphase fluorescence in situ
      hybridization performed on paraffin-embedded tissue sections with 12q15 probes
      and a 6p21 probe demonstrated no chromosomal rearrangement. Sixty-nine cases of
      this type of tumor arising in the breast have been described previously. Using
      imaging procedures, the tumor has occasionally been misdiagnosed as malignant
      clinically and even pathologically in frozen section diagnosis. Careful diagnosis
      based on paraffin sections is required to avoid unnecessary aggressive surgery,
      and pathologists should include pleomorphic adenoma in the differential diagnosis
      of a demarcated, juxtaareolar, small hard mass.

PMID- 15991842
TI  - A case of primary biliary cirrhosis accompanied with fibrinogen storage disease.
AB  - We report the first case of primary biliary cirrhosis (PBC) accompanied by
      fibrinogen storage disease (FSD). A 50-year-old Japanese woman had been treated
      for numbness of her right-side extremities for 5 years. Mildly elevated serum
      levels of alkaline phosphatase and gamma-glutamyl transferase were detected. The
      titers of both anti-mitochondrial (x 320) and anti-mitochondrial M2 (x 84)
      antibodies were elevated. The biopsied liver specimen showed mononuclear cell
      infiltrate densely encircling the bile ducts, poorly developed epithelioid cell
      granuloma, and loss of integrity of bile duct organization, which permitted a
      diagnosis of stage I PBC according to Scheuer's histologic classification. In
      addition, round to oval, eosinophilic, homogenous intracytoplasmic inclusions,
      several microm in average size, with a surrounding halo were found in the vast
      majority of hepatocytes. These inclusions were negative for the periodic acid
      Schiff reaction. In immunohistochemistry, the inclusions were positive for
      fibrinogen and complement C3c, but not for HBs antigen and alpha1-antitrypsin.
      These findings were identical to FSD. To investigate the mechanism(s) of abnormal
      fibrinogen storage, immunostaining for heat shock protein 70 and ubiquitin was
      performed. The former was detected in all intracytoplasmic inclusions, whereas
      the latter was detected in only some inclusions, suggesting a partial loss of
      ubiquitin expression.

PMID- 15991843
TI  - Dedifferentiated liposarcoma with extensive lymphoid component.
AB  - An unusual variant of dedifferentiated liposarcoma with extensive lymphocytic
      component is described. A 71-year-old patient suffered from a relapse of an
      atypical lipomatous tumor/well-differentiated liposarcoma with early micronodular
      (low-grade) dedifferentiation, which had been resected 4 years before. The
      relapse revealed features of a dedifferentiated liposarcoma with spindle-cell,
      partly pleomorphic dedifferentiation and osseous metaplasia. Clearly separated
      from the spindle-cell areas, an extensive homogeneously dense lymphoid
      (lymphocytic) tumor-component was evident, with relative abrupt transition to the
      well-differentiated liposarcoma component. Using immunohistochemistry and PCR,
      the lymphoid ("lymphoma-like") infiltrate proved to be a polyclonal lymphocytic
      proliferation. Fluorescence in situ hybridization (FISII) analysis revealed no
      signs of MDM2- and CDK4-gene amplification in the lymphoid areas, although within
      this mononuclear lymphoid population, large polymorphic nuclei displayed an
      amplified number of MDM2/CDK4 gene copies, indicating the presence of truly
      dedifferentiated tumor cells within the lymphoid component. The results favor a
      reactive lymphocytic infiltration versus a neoplastic one, which might be caused
      for example by chemoattractive agents. An extensive lymphoid "overgrowth" must be
      considered within the spectrum of unusual variants and in the differential
      diagnosis of dedifferentiated liposarcoma.

PMID- 15991844
TI  - Epithelioid malignant peripheral nerve sheath tumor. Report of a case with
      inflammatory infiltration.
AB  - The epithelioid malignant peripheral nerve sheath tumor (EMPNST) is a rare
      sarcoma originating from the supportive non-neuronal components of peripheral
      nerves. Our patient was a 75-year-old Japanese man who presented with complaints
      about pain and a mass in the left thigh. Characteristic histopathological
      features were large epithelioid-like cells closely resembling a malignant
      melanoma or another type of soft tissue tumor. Notable infiltration of
      neutrophils in the tumor was seen. Immunohistochemically, the tumor cells proved
      positive for S-100, NSE, GFAP, MBP, chromogranin A and synaptophysin, and
      negative for CEA, keratin, HMB-45, G-CSF, and GM-CSF. Tumor-related inflammatory
      infiltration may be caused by an autonomous production of some cytokines.
      However, these tumor cells were negative for G-CSF and GM-CSF so that the
      mechanism triggering inflammatory infiltration is unclear. Electron microscopy
      revealed the presence of an extracellular basal lamina, intermediate cell
      junctions, and numerous dense-cored granules in the cytoplasm. These findings
      suggested a schwannian derivation, consistent with the diagnosis of EMPNST. There
      have been reports on S-100 positivity and HMB-45 negativity of this tumor type,
      but to the best of our knowledge, this is the first description of an EMPNST
      positive for MBP, chromogranin A, and synaptophisin. Where unequivocal features
      are lacking, these markers might be useful for differential diagnosis.

PMID- 15991845
TI  - [Role of prostaglandins in the pathogenesis of stomach ulcer and gastropathy
      caused by non-steroid anti-inflammatory drugs].
AB  - GOAL OF THE STUDY: To assess the pathogenetic significance of the prostaglandin
      level in the mucous coat of the stomach in patients with osteoarthritis who take
      several types of non-steroid anti-inflammatory drugs. MATERIALS AND METHODS: The
      study of the E2 and F2alpha (prostaglandins levels in the blood and mucous coat
      of the stomach was conducted in 20 patients with stomach ulcer, 15 patients with
      osteoarthritis taking diclofenac and 16 patients taking celecoxib. RESULTS: It
      has been shown that the E2 prostaglandin level decreases both in the blood and in
      the mucous coat of the stomach in patients with stomach ulcer. If non-steroid
      anti-inflammatory drugs are taken, the E2 prostaglandin level in the mucous coat
      of the stomach decreases even if there are no erosive-ulcerous lesions. If
      celecoxib is taken, the changes in the prostaglandin E2 and F2beta level in the
      mucous coat of the stomach are less marked. Patients with the low content of E2
      prostaglandin in the mucous coat of the stomach develop gastropathies more
      frequently even before non-steroid anti-inflammatory drugs are taken. CONCLUSION:
      Reduction of the basal prostaglandin secretion in the mucous coat of the stomach
      is a risk factor of non-steroid anti-inflammatory drugs gastropathy appearance.
      The use of selective COX-2 inhibitors makes it possible to reduce the risk of
      gastropathy appearance in this group of patients.

PMID- 15991846
TI  - [Study of the motor function of the function and duodenum at diseases of the
      biliary excretion system].
AB  - For the last few years the disorders of the motor function of the
      gastrointestinal tract are subjects of interest for investigators and physicians.
      The article presents an analysis of different abnormalities of the motor function
      of the stomach and duodenum made by gastroduodenoscintigraphy in patients with
      the biliary tract disorders. The most frequent types of motor gastric and
      duodenal dysfunctions are discussed in patients with gall bladder dysfunction,
      chronic cholescystitis, and patients after cholecystectomy.

PMID- 15991847
TI  - [Use of the Gepon immunomodulator for ulcerative colitis treatment].
AB  - The efficacy of the Gepon immunomodulator was studied in 36 patients with
      ulcerative colitis (UC) having distal lesions in the resistant form. Taking into
      account the fact that immunological abnormalities play the main role in UC
      pathogenesis, the drug with immunomodulatory action was used for overcoming
      resistance to basic anti-inflammatory drugs. The clinical and immunological
      reaction to the used drugs was found to be ambiguous. Most of the patients
      (83.3%) had clinical and endoscopic amelioration after taking Gepon and managed
      to overcome the resistance to basic anti-inflammatory drugs.

PMID- 15991848
TI  - [Non-alcohol steatohepatitis].

PMID- 15991849
TI  - [Dynamics of clinical symptoms and indices of visceral sensitivity in patients
      with the irritated bowels syndrome treated with meteospasmyl].

PMID- 15991850
TI  - [Treatment of the irritable bowel syndrome from the point of conclusive
      medicine].
AB  - For many years the irritable bowel syndrome therapy was based only on an
      empirical approach. A lot of information has appeared for this period, which
      allows making a judgment about the efficacy of either of the ways of the
      functional bowel disorders treatment. A part of them was not approved in the
      course of clinical testing. At the same time, new high-performance ways of
      treatment appeared. This article presents an analytical survey of the irritable
      bowel syndrome pharmacotherapy. It also shows the role of diet, spasmolysants,
      psychotherapy, tricyclic antidepressants, serotonin reuptake inhibitors, HT3
      antagonists and HT4 agonists.

PMID- 15991851
TI  - [Prospects of the biological therapy of inflammatory bowel diseases].

PMID- 15991852
TI  - [Fermentative mechanisms in the ethiopathogenesis of stomach ulcer formation].

PMID- 15991853
TI  - [Videolaparoscopy in the treatment of peritoneal commissures in the abdominal
      cavity].
AB  - The article describes the results of the examination and treatment of patients
      with peritoneal commissures in the abdominal cavity. The study was conducted by
      members of the Hospital Surgery Chair No. 1 of the Russian State Medical
      University based on the Municipal Clinical Hospital No. 15. The article also
      describes and analyzes the up-to-date methods of the examination of patients
      having peritoneal commissures in the abdominal cavity and results of
      videolaparoscopical adheolysis. The algorithm of the examination of patients with
      peritoneal commissures was developed; indications for videolaparoscopical
      adheolysis in the emergency and selective surgery were studied and defined.

PMID- 15991854
TI  - [Immediate and long-term results of the rectal prolapse surgery].

PMID- 15991855
TI  - [Erosive and ulcerous conditions in children and teenagers].

PMID- 15991856
TI  - [Muriatic secretion and acid-proteolytic activity of the stomach in vivo].
AB  - The study of the basal (BAP) and stimulated (SAP) acid production effect on the
      average daily acidity and speed of proteolysis in the stomach in vivo was
      conducted in 498 patients with various functional states of the stomach. It was
      established that the aforesaid muriatic secretion indices influence the acidity
      and speed of proteolysis in natural conditions of digestion only within the low
      and normal range of their values. In the condition of HCl hypersecretion, the
      dependence between the muriatic secretion and acidity and proteolytic stomach
      activity in vivo gets lost. This can be explained by the autoregulation effect
      supporting the introgastral pH optimal for pepsin activity irrespective of the
      intensity of the acid glands hyperplasia.

PMID- 15991857
TI  - [Ectopia of the pancreas in the antral part of the stomach and duodenal cap].

PMID- 15991858
TI  - [Hirschsprung's disease in adults: state of the problem and description of a rare
      clinical case].
AB  - The article presents the current ideas of etiology, pathogenesis, clinical
      picture, diagnostics and treatment of the congenital disease of the large
      intestine--Hirschsprung's disease of adults. In addition, the article describes a
      rare clinical case of the Hirschsprung's disease in two sisters from the same
      family.

PMID- 15991859
TI  - [Prevalence of the lactase deficiency among the population of the northwestern
      region of Russia].
AB  - The article presents the authors' and literature data on the prevalence of the
      lactase deficiency among the nations of the Finn-Ugric language group (Finns,
      Karelians, Vepses, Izhors, Estonians), Eastern Slavs (Russians, Ukrainians,
      Belorussians) living in the northwestern region of Russia. The lactase deficiency
      has been established: among Russians--16%, Belorussians--15%, Ukrainians--13%,
      Finns--22%, Karelians--20%, Vepses--20%, Izhors--20%, Estonians--23%.
      Confirmations of the cultural and historical hypothesis of the lactase deficiency
      prevalence have been found. It has been shown that under certain ecological
      conditions the nature of human nutrition during a continuous period of history
      can produce significant genetic changes in the population.

PMID- 15991860
TI  - Cerebral palsy: towards developmental neuroscience.

PMID- 15991861
TI  - Exploring the origins of developmental disorders.

PMID- 15991862
TI  - Motor coordination, empathy, and social behaviour in school-aged children.
AB  - Children with motor coordination problems are known to have emotional
      difficulties and poor social skills. The current study investigated whether
      children with poor motor ability have poor emotion recognition skills, and
      whether these could be linked to problems in social behaviour. It was
      hypothesized that difficulties in empathic ability might be related to the poor
      visuo-spatial processing ability identified in children with developmental
      coordination disorder (as defined by the American Psychiatric Association). The
      relationship between motor coordination, emotion recognition, and social
      behaviour was examined in a sample of 234 children (113 males, 121 females; mean
      age 9y 7mo, [SD 1y 8mo] age range 6y 8mo to 12y 11mo). From this sample two
      groups of 39 children each (17 females, 22 males), one group with motor
      difficulties (mean age 9y 11mo [SD 2y], range 6y 11mo to 12y 11mo) and the other
      of control children (mean age 10y [SD ly 11mo], range 6y 11mo to 12y 11mo),
      matched for age and sex, were compared using a set of six emotion recognition
      scales that measured both verbal and perceptual aspects of empathic ability.
      Children with motor difficulties were found to perform more poorly on scales
      measuring the ability to recognize static and changing facial expressions of
      emotion. This difference remained even when visuo-spatial processing was
      controlled. When controlling for emotion recognition and visuo-spatial
      organization, a child's motor ability remained a significant predictor of social
      behaviour.

PMID- 15991863
TI  - Cognitive functions in classic phenylketonuria and mild hyperphenylalaninaemia:
      experience in a paediatric population.
AB  - A study of 37 individuals with phenylketonuria (PKU; 17 females and 20 males,
      mean age 9y 9mo (standard deviation [SD] 5y 3mo), range 2y 8mo to 19y 4mo; and 35
      individuals with hyperphenylalaninaemia (HPA; 20 females, 15 males, mean age 7y
      10mo [SD 3y 2mo], range 2y 8mo to 17y 3mo) compared with 29 healthy controls (14
      females and 15 males, mean age 9y 8mo [SD 4y 9mo], range 2y 6mo to 18y 10mo) was
      performed. The aim was to assess cognitive function in persons with HPA and to
      investigate the relation between cognitive function in PKU and the metabolic
      control of patients. A wide variety of neuropsychological tests was employed.
      Those with PKU showed lower values in intelligence and in visuo-spatial, fine
      motor, executive, and attention functions when compared with a control
      population. Plasma phenylalanine values from the first 6 years of life were
      negatively associated with intelligence and other cognitive functions. Executive
      function scores were significantly lower when comparing HPA patients with the
      control group. It was concluded that individuals with PKU under dietary treatment
      may present slightly decreased cognitive function scores when compared with
      control individuals, while those with HPA have scores mostly similar to those of
      controls, except for executive function tests. Good metabolic control of PKU
      seems necessary to prevent cognitive function impairments, especially during the
      first 6 years of life.

PMID- 15991864
TI  - Balance control: sex and age differences in 9- to 16-year-olds.
AB  - This study investigated sex and age differences in standing balance. Movement of
      the centre of pressure (COP) was calculated from ground reaction force data
      collected from a force platform during bipedal stance with eyes open and eyes
      closed. Three groups of 60 children, with 30 girls and 30 boys in each, were
      assessed. Mean ages of each group were as follows: 9 years 11 months (standard
      deviation [SD] 3mo); 12 years 11 months (SD 2mo); and 15 years 11 months (SD 3mo)
      respectively. Summary sway parameters and frequency domain variables were
      calculated in the anteroposterior and mediolateral directions. Boys exhibited
      greater COP movement than girls at 9 to 10 years of age. Age-related
      'improvements' in sway occurred in boys, thus some aspects of postural control
      are still developing after 9 to 10 years of age. As very little age-related
      difference was seen in girls, boys may lag behind somewhat in terms of developing
      postural control. Thus there is a need to study the sexes separately when
      investigating balance in children.

PMID- 15991865
TI  - Effect of balance training on muscle activity used in recovery of stability in
      children with cerebral palsy: a pilot study.
AB  - This study explored possible neural mechanisms that contribute to improvements in
      balance control produced by reactive balance training in children with cerebral
      palsy (CP). Six children with CP (four males, two females; mean age 9y 4mo), two
      with spastic hemiplegia (Gross Motor Function Classification System [GMFCS] level
      I) and four with spastic diplegia (GMFCS level II,) were given 5 days of
      intensive training in reactive balance control (100 perturbations per day on a
      moveable force platform). Surface electromyography was used to characterize
      changes in neuromuscular responses pretraining, immediately posttraining, and 1
      month posttraining. Training in reactive balance control resulted in improvements
      in directional specificity of responses (a basic level of response organization)
      and other spatial/temporal characteristics including: (1) faster activation of
      muscle contraction after training, allowing children to recover stability faster;
      (2) emergence of a distal-proximal muscle sequence; and (3) improved ability to
      modulate the amplitude of muscle activity (increased amplitude of agonist and
      decreased amplitude of antagonist, reducing coactivation). Each child with
      spastic hemiplegia or diplegia showed a different combination of factors that
      contributed to improved performance; the level of change in neural factors
      depended on the severity of involvement of the child: hemiplegia vs diplegia, and
      level of involvement within each diagnostic category.

PMID- 15991866
TI  - Assessing functional differences in gross motor skills in children with cerebral
      palsy who use an ambulatory aid or orthoses: can the GMFM-88 help?
AB  - The purpose of this study was to determine whether the Gross Motor Function
      Measure (GMFM-88) is sensitive to within-child changes in function as a result of
      children who use an ambulatory aid or orthoses in comparison with unaided or
      barefoot function. Data from 257 children (140 males, 117 females) with cerebral
      palsy (CP) were analyzed from a 5-year longitudinal study. The children's age
      ranged from 2 to 15 years (mean 7y 4mo; SD 2y 11mo), and type of CP, included
      spastic (n=206 [80.2%1), dyskinetic (n=13 [5.1%]), ataxic (n=9 [3.5%]), hypotonic
      or mixed (n=27 [10.5%]), and those missing (n=2 [0.8%]), and in motor ability
      (Gross Motor Function Classification System [GMFCS] levels I, n=40, II, n=34, m,
      n=93, IV, n=76, and V, n=14). Paired t-tests between barefoot and aided
      assessments showed significantly higher GMFM-88 total scores overall (n=257) for
      aided assessment and for three subgroups (ankle-foot orthoses only, ambulatory
      aid only, ankle-foot orthoses plus ambulatory aid), providing evidence that the
      GMFM-88 is sensitive to functional changes as a result of using an aid and/or
      orthoses. With regard to changes within the orthoses-only group, significant
      changes varied by GMFCS level. The GMFM-88 might provide a clinically useful tool
      to help in understanding the impact of ambulatory aids and orthoses on gross
      motor skills of children with CP.

PMID- 15991867
TI  - Botulinum toxin A and upper limb functional skills in hemiparetic cerebral palsy:
      a randomized trial in children receiving intensive therapy.
AB  - The objective of this study was to determine whether the use of intramuscular
      botulinum toxin A (BTX-A) increases upper limb function and skills in the context
      of a specific therapy programme in children with hemiparetic cerebral palsy.
      Twenty children (nine females, 11 males) aged 4 to 16 years who were thought
      likely to benefit from BTX-A treatment were included. After matched pairs were
      made, on the basis of Zancolli grade and age, randomization took place. All
      patients were given structured rehabilitation (physiotherapy and occupational
      therapy three times a week for 6 months), and half of the patients received
      intramuscular BTX-A. No placebo injections were given in the control group.
      Participants were assessed at baseline, at 2 and 6 weeks, and at 3, 6, and 9
      months after injection. The Ashworth scale, active range of motion of arm joints,
      the Melbourne assessment of upper limb function, the Pediatric Evaluation of
      Disability Inventory, and the nine-hole peg test were used for outcome
      measurement. Observers were blinded for treatment allocation only for scoring the
      Melbourne test. The children in the treatment group showed a clinically relevant
      increase in active dorsal flexion, and tone reduction of the wrist. For the
      functional outcome measures, no statistically significant differences between the
      groups could be demonstrated. Intramuscular BTX-A added to an intensive therapy
      programme reduces impairment for at least 9 months; the effect on activity level
      is still uncertain.

PMID- 15991868
TI  - Diagnosis and management of Duchenne muscular dystrophy in a developing country
      over a 10-year period.
AB  - Clinical data on Duchenne muscular dystrophy (DMD) are lacking in developing
      countries. The objective of this study was to delineate the demographic
      characteristics, investigations, and outcome of 21 Malaysian males diagnosed with
      DMD over a period of 10 years. Mean age presentation was 3 years 8 months (SD
      23mo; range 10 to 84mo), mean duration from first presentation to diagnosis was
      3y 7mo (SD 26mo; range 5 to 84) and the mean age for loss of ambulation was 11
      years (SD 25mo; range 102 to 168). There was family history of DMD in five of the
      21 patients. Muscle biopsy showed confirmatory findings of DMD in the 16 patients
      tested. Molecular genetic analysis showed dystrophin gene deletions in 11 of
      these 16 patients. Four and seven of the students stopped schooling and had
      learning difficulties, respectively; only nine had satisfactory school
      performances. Eight out of 14 patients evaluated were classified as having severe
      to total dependency levels on the modified Barthel Index for activities of daily
      living assessment. DMD is associated with significant medical and social needs
      for a developing country such as Malaysia. Earlier referral, genetic counselling,
      and provision of support and rehabilitative services are the main priorities.

PMID- 15991869
TI  - Myotonic dystrophy: muscle involvement in relation to disease type and size of
      expanded CTG-repeat sequence.
AB  - This study aimed to: classify a cohort of children and adolescents with myotonic
      dystrophy (dystrophia myotonica: DM) into congenital and childhood onset forms;
      estimate CTG expansion size; and quantify muscle strength, contractures, and
      motor function in children with DM and compare results with those of controls.
      Participants were clinically examined, medical records were reviewed, and
      isometric muscle strength, contractures, and motor function were measured.
      Participants were: 42 children with DM (18 females, 24 males; mean age 8y 9mo [SD
      4y 7mo], range 10mo to 17y) and 42 age- and sex-matched, healthy controls.
      Children with DM were divided into three groups: severe congenital (n=13), mild
      congenital (n=15), and childhood (n=14). Children with childhood DM were
      significantly weaker than controls (wrist and ankle dorsiflexors [p=0.0044,
      p=0.0044 respectively]; hip abductors and flexors [p=0.0464, p=0.0217]; and knee
      flexors and extensors: [p=0.0382, p=0.0033]). Children with mild congenital DM
      were significantly weaker than controls in all assessed muscle groups.
      Contractures and skeletal deformities were more frequent at time of investigation
      than at birth, suggesting that foot and spine deformities in particular increase
      over time. Motor function score was significantly lower for children with DM than
      for controls. Children with severe congenital DM had the lowest motor function,
      with correlation between motor function and size of CTG repeat (p=-0.743).
      Children found jumping, heel standing, and head lifting the most difficult items
      to perform but few had difficulty walking, running, or stair climbing. DM in
      children is a heterogeneous disorder with a wide spectrum of muscle involvement,
      and owing to increased risk of contractures and skeletal deformities, regular
      follow-ups are recommended.

PMID- 15991870
TI  - Asymptomatic cerebellar atrophy after acute enteroviral encephalitis.
AB  - We report on a 13-year-old male who had acute enteroviral encephalitis causing
      cerebellar symptoms at the age of 10 years. Magnetic resonance imaging (MRI)
      showed no abnormalities. Clinically he appeared to be recovered completely after
      6 months. Twenty-three months after the recovery, MRI was performed because he
      presented with slight lower-limb and truncal ataxia experienced as lack of foot
      coordination while playing football or riding a bicycle. MRI demonstrated severe
      cerebellar atrophy. Clinically he recovered completely in 10 days. Only
      sophisticated electrophysiological methods revealed cerebellar dysfunction. The
      case provides evidence for the plasticity of cerebellar regulatory structures
      involved in the coordination of fine movements. It seems that in childhood the
      slow, isolated disintegration of cerebellar systems can be compensated for by
      upper thalamic or telencephalic connections, in a similar way to a congenital
      deficit of the cerebellum.

PMID- 15991871
TI  - A neonatal diagnosis of congenital chronic inflammatory demyelinating
      polyneuropathy.
AB  - We report a female infant noticed by her mother to have reduced movements of her
      right wrist and left foot at birth. This female presented to the Accident and
      Emergency Department of Queen Elizabeth Hospital, London, UK, aged 6 weeks, with
      significant weakness of her right wrist and left foot. Her clinical history also
      revealed sudden diminution in fetal movements 2 weeks before delivery, consistent
      with neuropathology in utero and neuromuscular deficit in the immediate postnatal
      period. An initial examination revealed generalized hypotonia, areflexia, and
      paucity of movements. Electrophysiological studies suggested demyelinating
      polyneuropathy; sural nerve biopsy confirmed a diagnosis of chronic inflammatory
      demyelinating polyneuropathy (CIDP). With the results and the pre- and postnatal
      clinical history, we believe this to be the first reported individual with
      congenital CIDP confirmed in the neonatal period. We describe the treatment and
      outcome up to the age of six years.

PMID- 15991872
TI  - Autism interventions: a critical update.
AB  - As yet, there is no aetiology-based intervention for autistic spectrum disorders
      (ASD); despite this, parents and professionals still need to make informed
      decisions regarding treatment options for children with ASD. This paper seeks to
      evaluate widely used interventions according to specific research criteria.
      Interventions presented are grouped into psychoeducational/behavioural
      approaches, psychopharmacological interventions, and the less traditional or
      complementary approaches. The conclusions are less than favourable: while some
      interventions do have empirical support, others have been proven to have no
      positive effects, and furthermore, there are no robust data favouring one
      approach over the others. Nevertheless, several criteria for choosing between
      treatment options are briefly discussed.

PMID- 15991873
TI  - Savant talent.
AB  - The notion of talent is an elusive concept but there appears to be sound evidence
      that both savants and experts share important qualities. Brief descriptive
      accounts of the talents displayed by savants are presented, along with a
      discussion of intelligence, implicit learning, and the organization of knowledge.
      Cognitive theories helpful in understanding exceptional abilities in people with
      autism are also discussed. It is concluded that a certain cognitive style, i.e.
      weak coherence, may predispose individuals to develop their talents. Although it
      would be interesting to speculate that some great artists and mathematicians show
      a similar degree of obsessive preoccupation and a cognitive style reminiscent of
      autistic spectrum disorder, presumably as a strategic mechanism, there is, as
      yet, little research on the subject.

PMID- 15991874
TI  - 'Pyruvate dehydrogenase deficiency presenting as dystonia and responding to
      levodopa'.

PMID- 15991875
TI  - Zero anaphora: transfer of reference tracking strategies from Chinese to English.
AB  - English contains many nominals that would be absent in Chinese because Chinese
      makes greater use of "zero anaphora," which is an empty grammatical slot in a
      sentence standing for a previously mentioned referent. Native Chinese and native
      English speakers were compared in comprehending modified English passages from a
      standardized reading test with nominals deleted that would be absent in Chinese.
      In three experiments, Chinese speakers showed superior comprehension as measured
      by objective multiple-choice questions in this case, but not when no words were
      deleted or when nominals were deleted that would not be absent in Chinese. These
      results imply that native Chinese speakers develop reference tracking strategies
      that they transfer to comprehending English.

PMID- 15991876
TI  - The semantics of space: experiential and linguistic aspects of selected English
      spatial terms.
AB  - To investigate relationships between spatial terms and the human experience of
      space, participants in three separate experiments were asked to sort 35 English
      spatial terms into groups on the basis of which items seemed most similar to one
      another. Participants also were asked to provide a descriptive rationale for each
      of their groupings. Once all groupings were recorded, they were subject to
      hierarchical clustering analysis and results of all three studies produced five
      different clusters centering around issues of (1) barrier and passage, (2)
      distance, (3) embodiment, (4) boundary and containment, and (5) verticality.
      Meanings for each cluster were named on the basis of participant descriptions and
      from independent evaluations made by the research team. Using these thematic
      meanings as a guide, a first-person description of spatial experience was
      developed and related to current analyses of the Whorf Hypothesis concerning
      issues of spatial experience and memory.

PMID- 15991877
TI  - Interjections in interviews.
AB  - A psycholinguistic hypothesis regarding the use of interjections in spoken
      utterances, originally formulated by Ameka (1992b, 1994) for the English
      language, but not confirmed in the German-language research of Kowal and
      O'Connell (2004 a & c), was tested: The local syntactic isolation of
      interjections is paralleled by their articulatory isolation in spoken utterances
      i.e., by their occurrence between a preceding and a following pause. The corpus
      consisted of four TV and two radio interviews of Hillary Clinton that had
      coincided with the publication of her book Living History (2003) and one TV
      interview of Robin Williams by James Lipton. No evidence was found for
      articulatory isolation of English-language interjections. In the Hillary Clinton
      interviews and Robin Williams interviews, respectively, 71% and 73% of all
      interjections occurred initially, i.e., at the onset of various units of spoken
      discourse: at the beginning of turns; at the beginning of articulatory phrases
      within turns, i.e., after a preceding pause; and at the beginning of a citation
      within a turn (either Direct Reported Speech [DRS] or what we have designated
      Hypothetical Speaker Formulation [HSF]. One conventional interjection (OH)
      occurred most frequently. The Robin Williams interview had a much higher
      occurrence of interjections, especially nonconventional ones, than the Hillary
      Clinton interviews had. It is suggested that the onset or initializing role of
      interjections reflects the temporal priority of the affective and the intuitive
      over the analytic, grammatical, and cognitive in speech production. Both this
      temporal priority and the spontaneous and emotional use of interjections are
      consonant with Wundt's (1900) characterization of the primary interjection as
      psychologically primitive. The interjection is indeed the purest verbal
      implementation of conceptual orality.

PMID- 15991878
TI  - Learning verbs without arguments: the problem of raising verbs.
AB  - This paper addresses the problem of learning the class of raising verbs (e.g
      seem). These verbs are potentially problematic for learners in that unlike
      typical main verbs these verbs do not stand in a semantic relation with any Noun
      Phrase (NP) arguments. Moreover, a second class of verbs, known as control verbs,
      shares certain distributional properties with raising verbs, but the two verb
      classes differ in important structural properties. The central problem addressed
      here is that of how a learner would distinguish raising verbs from control verbs,
      given their partial overlap in distribution. A series of experiments with English
      speaking adults using a fill-in-the-blank questionnaire revealed two main types
      of cues that led participants to distinguish the two verb classes: inanimate NPs
      and semantically empty subjects ("it's raining") yielded the highest proportion
      of raising verb responses from adults, while animate NPs paired with eventive
      predicates yielded a high rate of control verb responses. On the basis of these
      results, suggestions are made as to how one should study the learning of these
      verbs in children.

PMID- 15991880
TI  - Effect of food on the pharmacokinetic profile of eslicarbazepine acetate (BIA 2
      093).
AB  - OBJECTIVE: To investigate the effect of food on the pharmacokinetics of
      eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel
      antagonist. MATERIAL AND METHODS: Single-centre, open-label, randomised, two-way
      crossover study in 12 healthy subjects. The study consisted of two consecutive
      treatment periods separated by a washout of 14 days or more. In each of the study
      periods subjects were administered a single dose of eslicarbazepine acetate 800
      mg following either a standard high-fat content meal or 10 hours of fasting.
      RESULTS: Eslicarbazepine acetate was rapidly and extensively metabolised to BIA 2
      005. Maximum BIA 2-005 plasma concentrations (C(max)) in fed (test) and fasting
      (reference) conditions were, respectively, 12.8 +/- 1.8 microg/mL and 11.3 +/-
      1.9 microg/mL, and the areas under the plasma concentration time curve from 0 to
      infinity (AUC(infinity)) were, respectively, 242.5 +/- 32.1 microg.h/mL and 243.6
      +/- 31.1 microg.h/mL (arithmetic mean +/- SD). The point estimate (PE) and 90%
      confidence interval (90% CI) of the test/reference C(max )geometric mean ratio
      were 1.14 and 1.04, 1.25, respectively; for the AUC(infinity) ratio, the PE and
      90% CI were 1.00 and 0.95, 1.04, respectively. Bioavailability of eslicarbazepine
      acetate administered in fed and fasting conditions was similar and bioequivalence
      is accepted for both AUC(infinity) and C(max) because the 90% CI lies within the
      acceptance range of 0.80-1.25. No statistically significant differences were
      found in time of occurrence of C(max). CONCLUSION: The presence of food had no
      significant effect on the pharmacokinetics of eslicarbazepine acetate and
      therefore this new voltage-gated sodium channel antagonist may be administered
      without regard to meals.

PMID- 15991879
TI  - Comparison of the analgesic effects of a fixed-dose combination of orphenadrine
      and diclofenac (Neodolpasse) with its single active ingredients diclofenac and
      orphenadrine: a placebo-controlled study using laser-induced somatosensory-evoked
      potentials from capsaicin-induced hyperalgesic human skin.
AB  - OBJECTIVE: The aim of this study was to investigate the analgesic efficacy of
      Neodolpasse, a fixed-dose combination of orphenadrine and diclofenac, compared
      with those of its single active ingredients in a human pain model. METHODS: The
      study was designed as a randomised, double-blind, placebo-controlled, four-period
      crossover study. Twenty-four healthy female and male subjects received single
      infusions of Neodolpasse, orphenadrine, diclofenac or saline solution over 60
      minutes. Infusions were separated by a 1-week washout period. Neurogenic
      inflammation and hyperalgesia were induced by topical occlusive application of a
      1% capsaicin solution for 30 minutes on defined skin areas on the back. The pain
      response to CO2 laser pulses applied to the capsaicin-pretreated skin was
      measured by event-related vertex EEG recordings. This allowed us to study the
      influence of a single infusion on the central P2- and peripheral N1-components of
      laser-induced somatosensory-evoked potentials (LSEP) as a measure of pain
      response. RESULTS: Although none of the active treatments had a significant
      effect on the peripheral N1-component, all active treatments reduced the P2
      component of the LSEP, reflecting central/spinal analgesic (anti-hyperalgesic)
      effects. These effects were statistically significant for orphenadrine (p <
      0.0001) and for the combination of orphenadrine and diclofenac (p < 0.0013). The
      single ingredient diclofenac reduced the P2-component by a value just below
      clinical relevance (p < 0.0848). CONCLUSION: This study demonstrated the efficacy
      of Neodolpasse in a human pain model. The observed effect was mainly caused by
      central mechanisms and was found to be superior for the fixed-dose combination of
      orphenadrine and diclofenac compared with the individual ingredients. Both
      components contributed to the effect of the combination in an additive fashion,
      which can be explained by the different molecular mechanisms of action of each
      drug.

PMID- 15991882
TI  - BG 12: BG 00012, BG 12/Oral Fumarate, FAG-201, second-generation fumarate
      derivative--Fumapharm/Biogen Idec.
AB  - Fumapharm AG has developed a second-generation fumarate (fumaric acid)
      derivative, BG 12 [BG 00012, FAG-201, BG 12/Oral Fumarate], for the oral
      treatment of psoriasis. Biogen Idec is currently evaluating the product in
      clinical trials as an oral treatment for multiple sclerosis (phase II) and
      psoriasis (phase III) trials.BG 12 has an immunomodulatory mechanism of action.
      It seems that this product has been developed to reduce the adverse effects
      associated with a first-generation product containing fumaric acid esters (mixed
      dimethylfumarate and monoethylfumarate salts), Fumaderm. Fumaderm was approved in
      Germany in August 1994 and is currently the leading oral systemic therapy for
      moderate-to-severe psoriasis in Germany. One of the problems associated with
      Fumaderm capsules has been its gastrointestinal adverse effects (including
      diarrhoea and nausea). In September 2003, Biogen (now Biogen Idec) licensed
      exclusive worldwide rights (excluding Germany) from Fumapharm to develop and
      market BG 12. Biogen plans to collaborate with Fumapharm to accelerate phase III
      development for psoriasis and the registration programme worldwide. Financial
      terms of the agreement were not disclosed. Development plans for BG 12 include
      other autoimmune and inflammatory disorders, such as multiple sclerosis. In
      November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen Idec.
      Fumapharm completed phase II trials of this second-generation fumarate derivative
      for psoriasis prior to licensing of the product to Biogen, also with positive
      results.

PMID- 15991881
TI  - A randomised, controlled comparison of low-dose polyethylene glycol 3350 plus
      electrolytes with ispaghula husk in the treatment of adults with chronic
      functional constipation.

PMID- 15991883
TI  - Clindamycin/tretinoin: clindamycin phosphate/tretinoin gel.
AB  - Connetics Corporation (USA) has licensed a first-in-class, dual-action 1%
      clindamycin/0.025% tretinoin aqueous gel [Clindamycin phosphate/tretinoin gel,
      Velac, Velac Gel] from Yamanouchi Europe BV. The product combines the anti
      inflammatory and antibacterial properties of clindamycin with the beneficial
      effects of tretinoin [all-trans-retinoic acid], and is in phase III trials for
      the treatment of acne. On 1 April 2005, Yamanouchi merged with Fujisawa to form
      Astellas Pharma. Connetics has exclusive development and commercialisation rights
      for clindamycin/tretinoin gel in the US and Canada, and has non-exclusive rights
      to the product in Mexico. Under the licensing agreement terms, Connetics
      initially paid Yamanouchi a dollar US 2 million licensing fee, as well as
      milestone payments and royalties on future products. In the fourth quarter of
      2002, a dollar US 2 million milestone payment was made to Yamanouchi following
      the initiation of pivotal phase III trials in the US and Canada, and in the third
      quarter of 2004 a dollar US 3 million milestone payment was made to Yamanouchi
      following the filing of an NDA to the US FDA. In March 2004, Connectics reported
      that clindamycin/tretinoin is approved in Europe. It appears that this approval
      was specifically for France. In October 2004, Connetics announced that the US FDA
      has accepted its NDA filing for clindamycin/tretinoin. Two pivotal phase III
      trials of clindamycin/tretinoin have been conducted in the US and Canada. These
      trials included 2219 patients with acne who received 12 weeks' treatment in the
      double-blind, placebo- and active-controlled trials. Results of these trials were
      reported in March 2004. Connetics anticipates launch of the product during mid
      2005. An action date of 25 June 2005 has been given by the FDA for it to respond
      to the NDA submission. Phase III trials in patients with acne in Europe have
      shown clindamycin/tretinoin gel to be as effective and safe as other leading
      topical therapies. Data from a combined analysis of six controlled efficacy and
      safety trials of clindamycin/tretinoin have been reported. The patent for
      clindamycin/tretinoin gel is held by Yamanouchi in the US and internationally.
      Other analysts, at CIBC World Markets, were quoted saying that Evoclin represents
      Connetics' 'first foray' into the acne market (followed by others, such as
      Velac), a market that has been valued at dollar US 1.7 billion, of which that for
      topical antibiotics is worth approximately dollar US 500 million.

PMID- 15991884
TI  - Hexyl aminolevulinate: 5-ALA hexylester, 5-ALA hexylesther, aminolevulinic acid
      hexyl ester, hexaminolevulinate, hexyl 5-aminolevulinate, P 1206.
AB  - Hexyl aminolevulinate [aminolevulinic acid hexyl ester, hexyl 5-aminolevulinate,
      5-ALA hexylester, hexaminolevulinate, Hexvix, Hexvix PD, Hexvix PDT, P 1206] is
      being developed by PhotoCure, a Norwegian company, for the diagnosis and
      treatment of bladder cancer. The current standard diagnosis of bladder cancer
      involves cystoscopic examination of urine and bladder washings and is combined
      with biopsy for better detection of low-grade malignancies. However, the method
      largely relies on the experience of the surgeon and often results in false
      negatives especially for low-grade malignancies and pre-cancerous tissues.
      Photocure believes that imaging with hexyl aminolevulinate (Hexvix) offers
      significant advantages over standard diagnostic methods for detection of bladder
      cancer and also can be used in combination with those to ensure the optimal
      diagnostic accuracy. PhotoCure's procedure for diagnosis of bladder cancer
      involves filling of the patient's bladder with hexyl aminolevulinate solution and
      allowing the active agent to accumulate in the cancerous tissue. Following
      bladder emptying, blue light illumination is applied to the bladder causing red
      fluorescence that is clearly visible, thus identifying the cancerous tissue.
      Imaging with hexyl aminolevulinate improves detection of bladder tumours and also
      can be used together with transurethral resection to check the completeness of
      tumour removal. PhotoCure is looking for the opportunity to out-license
      hexaminolevulinate for all regions except the Nordic regions. PhotoCure has
      proprietary rights for hexyl aminolevulinate from the Norwegian Radium Hospital.
      Under the terms of the agreement with the Norwegian Radium Hospital, PhotoCure
      gains an access to, and an option to acquire, all of the new photodynamic therapy
      technologies developed by the Norwegian Radium Hospital. For its part, PhotoCure
      provides research and development funding to the Norwegian Radium Hospital. This
      3-year agreement was extended in February 2003 until December 2006. PhotoCure and
      Karl Storz GmbH of Germany have signed a formal collaboration for the development
      and marketing of hexyl aminolevulinate (Hexvix) and Karl Storz's D-light system.
      The two systems will be used in the diagnosis of bladder cancer. PhotoCure and
      Karl Storz GmbH will jointly apply for a marketing approval of hexyl
      aminolevulinate (Hexvix) and Karl Storz' D-light system in the US for detection
      of bladder cancer. The D-light system is already approved in Europe. PhotoCure
      has also formed a collaborative agreement with the Swiss Federal Institute of
      Lausanne and the Municipal University Hospital in Lausanne. These institutions
      have conducted preclinical studies and some exploratory clinical research on the
      active ingredient of Hexvix in approximately 100 patients. The first MAA for
      hexyl aminolevulinate fluorescence was filed in Sweden, the reference member
      state, in December 2002, and was approved in September 2004. PhotoCure plans to
      launch hexyl aminolevulinate in Sweden in June 2005. Phase II clinical trials
      were conducted in 52 patients with known or suspected bladder cancer at the
      university clinics in Switzerland, Germany, Sweden and Norway. Clinical data
      suggests that hexyl aminolevulinate (Hexvix) is useful in the early diagnosis of
      bladder cancers allowing treatment to be performed at an earlier stage and, thus,
      improve the chance of a successful clinical outcome. The company believes that
      the data from the US phase III programme at 19 leading urology clinics and two
      multicentre European trials at 28 leading hospitals across nine countries, will
      sufficiently support an NDA with the US FDA. The US phase III programme with
      hexyl aminolevulinate was initiated in December 2001. The results from the first
      European multicentre study conducted in 19 centres in 286 patients confirmed the
      advantages of hexaminolevulinate fluorescence cystoscopy over standard white
      light cystoscopy in the detection of bladder cancer. The second multicentre phase
      III study at ten centres in Germany and the Netherlands in 146 patients with
      known or suspected bladder cancer was sucessfully completed in March 2003. The
      independent blind reviewer acknowledged that imaging with hexyl aminolevulinate
      would result in better treatment options in every fifth patient compared with
      standard cystoscopy. Hexaminolevulinate is also undergoing early feasibility
      studies for the diagnosis and treatment of gynaecological and gastrointestinal
      conditions. PhotoCure was granted a European patent No. 0820432 covering hexyl
      aminolevulinate, an active ingredient used in Hexvix for the diagnosis and
      treatment of bladder cancer. The company was also granted patents in Australia,
      China, the Czech Republic, New Zealand, Russia, Singapore, South Korea and the
      US.

PMID- 15991885
TI  - Icatibant: HOE 140, JE 049, JE049.
AB  - Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic
      bradykinin B2-receptor antagonist. It has a modified peptide structure, and is
      the first bradykinin receptor antagonist to act on the guinea-pig trachea without
      demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel
      (now sanofi-aventis). Jerini AG is seeking a worldwide partner for the
      development and marketing of icatibant for the treatment of refractory ascites in
      liver cirrhosis and seeking a partner in Asia, North America, South America and
      Australia for angioedema. In August 2004, Aventis merged with Sanofi-Synthelabo
      to form sanofi-aventis. Icatibant has shown an excellent safety profile in phase
      I studies. In December 2003, Jerini demonstrated positive results in the phase
      IIa study. Results obtained were statistically significant and clinically
      relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San
      Francisco, CA, USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb
      trials in this indication in the second half of 2004. It was announced in
      September 2004 by Jerini that a pivotal registration study, known as FAST 1 (For
      Angioedema Subcutaneous Treatment), had been initiated in the US and Canada. The
      protocol of a European study, known as FAST 2, was submitted to the authorities
      in September 2004. Jerini is currently conducting pivotal/registration trials for
      angioedema in the US, Canada and Europe. During the 3rd Annual BioPartnering
      North America Conference (BPN-2005), Jerini announced that it expects to complete
      registration trials in the second half of 2005/first half of 2006, with a launch
      of icatibant for HAE in 2007. The US FDA granted fast-track status to icatibant
      in July 2004 for the treatment of HAE. Effective December 2003, icatibant gained
      orphan drug status in the US for the same indication. Previously, in January
      2003, the European Agency for the Evaluation of Medicinal Products granted
      icatibant orphan drug status in Europe for the treatment of angioedema.

PMID- 15991886
TI  - Lubiprostone: RU 0211, SPI 0211.
AB  - Lubiprostone [RU 0211, SPI 0211] is a bicyclic fatty acid that acts as a chloride
      channel opener, increasing intestinal water secretion. Lubiprostone, an orally
      administered formulation, is one of a series of functional fatty acid compounds
      discovered by Dr Ryuji Ueno, and is currently undergoing development for the
      treatment of constipation, constipation-predominant irritable bowel syndrome (IBS
      C) and postoperative ileus with Sucampo Pharmaceutical's. Lubiprostone activates
      a specific chloride channel (CLC2) on cells lining the gut, thereby naturally
      increasing intestinal fluid secretion. The increased fluid level softens the
      stool, promotes spontaneous bowel movements, and reduces abdominal
      discomfort/pain and bloating. The chloride channel is a protein that controls
      cell membrane transport of chloride ion. Lubiprostone acts on the ClC-2 chloride
      channel, which is located in the apical intestinal membrane. In November 2004,
      Takeda Pharmaceuticals entered into a collaboration and licensing agreement for
      Lubiprostone with Sucampo Pharmaceuticals for the treatment of chronic
      constipation and constipation-predominant Irritable Bowel Syndrome (c-IBS). Under
      the terms of the agreement, Takeda received the right to market the product in
      the US and Canada, while Sucampo reserved the co-promotion rights for these
      countries. Takeda's wholly-owned US subsidiary, Takeda Pharmaceuticals North
      America Inc., will sell lubiprostone once the product is approved by the US FDA.
      Takeda will also receive an option for marketing rights in other territories,
      including Japan and Europe. Takeda and Sucampo agreed on the exclusive
      manufacturing and supply of Lubiprostone by R-Tech Ueno, Ltd, a member of the
      Sucampo Group. Sucampo has the potential to receive up to dollar US 210 million
      in initial and milestone payments, some of which are contingent upon the
      successful achievement of several milestones. Takeda will fund a major part of
      development costs not only for chronic constipation and c-IBS, but also for other
      indications in the gastroenterology field. Takeda will make royalty payments to
      Sucampo after the product is launched. In May 2005, Sucampo received dollar US 20
      million from Takeda Pharmaceutical as payment for achieving a development
      milestone of initiating a phase III clinical trial of lubiprostone to treat
      patients with constipation-predominant irritable bowel syndrome. Sucampo
      Pharmaceuticals submitted a new drug application (NDA) for lubiprostone to the
      FDA on 31 March 2005 for approval in the treatment of chronic idiopathic
      constipation (CIC) and associated symptoms in adults. Sucampo completed three
      long-term, open-label safety studies, which will support the NDA for
      lubiprostone, in treating constipation. Results from its second open-label safety
      study with lubiprostone were announced in February 2004, with the first two
      studies demonstrating long-term safety and sustained effectiveness in constipated
      subjects. In the US, the final phase III study for chronic constipation was
      completed in the fourth quarter of 2004. In November 2004, Sucampo announced
      completing a phase II safety and efficacy study of lubiprostone for the treatment
      of IBS-C. This study, which was initiated in April 2003, randomised 195 patients
      with documented IBS into four treatment groups (three doses of SPI 0211 and
      placebo) from 19 locations throughout the US.

PMID- 15991888
TI  - Making sense of asthma.
AB  - There is now a high probability that all the genes encoded in the human genome
      will have been sequenced by the year 2005, resulting in a massive increase in the
      identification of novel therapeutic targets. The use of new genomic sequence
      information in conjunction with antisense oligonucleotides is one means by which
      the gene products playing the most important roles in multifactorial diseases,
      such as asthma, can be identified. Subsequently, the antisense nucleotides
      themselves can be used as therapeutic agents, or drugs designed to control the
      activity of the relevant gene product.

PMID- 15991887
TI  - Rufinamide: CGP 33101, E 2080, RUF 331, Xilep.
AB  - Rufinamide [E 2080, CGP 33101, RUF 331, Inovelon, Xilep] is the lead compound in
      a series of five-substituted phenylalkyl-3- carbamoyl-4H-1,2,4-triazoles with
      anticonvulsant activity that was discovered by Novartis AG. Although the precise
      mechanism of action for rufinamide is unknown, it is known that it limits the
      firing of sodium-dependent action potentials in neurons, hinting at a membrane
      stabilising effect. Rufinamide is under regulatory review in Europe for epilepsy,
      and phase III trials in the same indication are underway with Eisai in the US. In
      February 2004, Eisai Co. Ltd announced that it had signed an in-licensing
      agreement with Novartis Pharma AG for the exclusive worldwide rights to
      manufacture, develop and market rufinamide for the treatment of epilepsy. Eisai
      submitted an MAA for rufinamide (Inovelon) as an adjunct therapy of seizures
      associated with Lennox-Gastaut Syndrome to the European Medicines Agency through
      the centralised procedure in March 2005. The drug also received orphan drug
      designation from the European commission in October 2004 for this indication.
      Eisai also plans to file for regulatory approval in the US. Rufinamide has
      demonstrated statistically significant efficacy as an adjunctive therapy in adult
      patients with epilepsy and in patients with seizures associated with Lennox
      Gastaut syndrome. Novartis stated in June 2001, prior to the licensing agreement
      with Eisai, that it had stopped development of rufinamide in the US, Japan and
      Europe for neuropathic pain (at phase II) and epilepsy (at phase III).

PMID- 15991889
TI  - Respirable antisense oligonucleotides as novel therapeutic agents for asthma and
      other pulmonary diseases.
AB  - Respirable antisense oligonucleotides (rAsONs) targeting discordantly expressed
      mediators of inflammation and/or bronchoconstriction and delivered to the lung
      via inhalation represent a new class of epigenetic-based therapeutics for asthma
      and other pulmonary diseases. The properties of these agents (solubility,
      chemical stability, rapid design based on primary DNA sequence information)
      combine synergistically with characteristics of the lung (non-invasive route of
      administration directly to the target organ, presence of uptake-modifying
      surfactant) to enhance the therapeutic potential of these oligonucleotide-based
      drugs. Their potential is further increased by the possibility of engineering
      antisense oligonucleotides whose effects are limited to the lung, reducing or
      avoiding the possibility of systemic toxicity.

PMID- 15991890
TI  - Antisense approach for the treatment of cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) is the most common viral opportunistic infection in
      patients suffering with acquired immunodeficiency virus (AIDS). HCMV is a
      systemic infection that may infect several sites in the body, including the
      retina, gastrointestinal tract, lungs, liver, and central nervous system.
      Retinitis is the most frequent manifestation of HCMV infection, occurring in 15
      40% of all patients. HCMV is progressive and destroys the retina, eventually
      leading to blindness. Although, there are several drugs available to treat this
      disease, they are often of limited efficacy and have significant side-effects.
      Antisense oligonucleotides represent a novel alternative to the currently
      available drugs. Due to their high affinity and specificity to target the HCMV
      RNAs, interest in antisense technology to treat HCMV infections has been intense
      during the past few years. Two antisense drugs are currently in clinical trials,
      ISIS 2922 (Formivirsen) and GEM 132.

PMID- 15991891
TI  - Bispecific antibodies for the treatment of tumours and infectious diseases.
AB  - Bispecific antibodies are in clinical and preclinical development for the
      treatment of various cancers and life-threatening infectious diseases. Designed
      to direct and enhance the body's immune response to specific tumours and
      pathogens, bispecific antibodies have shown promising results in Phase I and
      Phase II clinical trials, leading in some cases to complete or partial responses
      in cancer patients. These bispecific antibodies consist of a 'targeting' domain,
      typically a fragment of a monoclonal antibody that binds to a tumour, linked to a
      'triggering' arm that is specific for a molecule capable of mediating a
      phagocytic or lytic response by macrophages, natural killer cells, T-cells or
      other effector cells. By mediating an immune assault on tumours or pathogens,
      bispecific antibodies may also lead to antigen presentation and a vaccine-like
      response in patients. Over the next few years, we expect several bispecific
      antibodies to enter the late stages of clinical trials and ultimately emerge as
      new pharmaceutical products.

PMID- 15991892
TI  - Telomerase and telomere inhibitors in preclinical development.
AB  - Telomerase is an enzyme required by actively dividing cells to maintain the ends
      of chromosomes (telomeres). It is present in germline tissue, stem cells and
      cancer cells, but is repressed in somatic cells. Efforts are underway to exploit
      this selective expression of telomerase in cancer therapeutics. This review
      describes the status of telomerase research, which although at present
      predominantly preclinical, has the potential to enter clinical research.

PMID- 15991893
TI  - The therapeutic potential of the human cystic fibrosis transmembrane conductance
      regulator gene.
AB  - The cloning of the gene encoding the cystic fibrosis transmembrane conductance
      regulator (CFTR), mutations of which are responsible for the clinical onset of
      cystic fibrosis (CF), along with progress in understanding the interplay between
      CFTR functions and the CF cellular phenotype have prompted many investigators to
      explore the therapeutic potential of CFTR gene delivery to airway cells in CF
      patients. In the last four years, a large number of Phase I clinical trials have
      been started. The results from the very first trials, although mixed, showed that
      it was possible to transfer and express the CFTR gene, and in certain cases
      restore the functional electrophysiological properties of the diseased CF cells.
      These initial trials have been fundamental in encouraging more basic research on
      vector design to improve the safety and efficiency of persistent CFTR gene
      transfer, and to introduce novel ways of administration and new techniques to
      assess the potential therapeutic efficacy of functional gene expression. New
      Phase I clinical trials based on novel protocol design were therefore initiated.

PMID- 15991894
TI  - Insulin-like growth factor-I and parathyroid hormone: potential new therapeutic
      agents for the treatment of osteoporosis.
AB  - Millions of men and women worldwide are afflicted by osteoporosis. As this number
      is projected to increase over the next half century, attempts to forestall the
      disease process are being tested. Conventional therapies centre on maintaining
      bone mineral density (BMD) by blocking bone resorption. However, there is a
      growing need for drugs that can stimulate new bone formation (anabolic agents),
      thereby reducing future fracture risk. Both parathyroid hormone (PTH) and insulin
      like growth factor-I (IGF-I) have been the subject of numerous animal and human
      studies to determine whether these peptides have promise for the treatment of low
      bone mass. Although the mechanisms of action for these agents are not well
      delineated, each protein can activate the osteoblast and thereby enhance bone
      mass. The effects of these drugs on the osteoclast are less well defined. At the
      current time, there is considerably more interest in PTH than IGF-I, for several
      reasons. Firstly, animal studies with PTH are more impressive in terms of
      histomorphometry and biomechanics than IGF-I; secondly, PTH is specific for the
      skeleton whereas IGF-I is ubiquitous; and thirdly, human studies with PTH have
      been relatively devoid of significant side-effects. Large scale Phase III trials
      are now underway in the US and Europe. It is anticipated that at least one of
      these peptides may prove to have a role in the prevention and treatment of
      osteoporosis.

PMID- 15991895
TI  - Inhibition of cathepsin K--a novel approach to antiresorptive therapy.
AB  - Cathepsin K is a cysteine protease enzyme with high and specific expression in
      osteoclasts, the cells responsible for resorbing bone. Its discovery and the
      numerous lines of evidence that support a specialised role for cathepsin K in
      bone resorption are discussed. Inhibition of this enzyme would be anticipated to
      prevent bone resorption, and be of potential utility in diseases involving excess
      bone loss, such as osteoporosis. The pharmaceutical companies known to be
      involved in developing inhibitors of cathepsin K, and their progress to date, are
      described.

PMID- 15991896
TI  - Role of oestrogen in the treatment and prevention of Alzheimer's disease.
AB  - Alzheimer's disease (AD), the most common primary dementing disorder, results in
      devastating clinical and socio-economic consequences, and is a leading cause of
      death among the elderly. Despite recent advances in the neurobiology of AD,
      identification of effective treatment strategies has remained frustratingly
      elusive. Administration of currently available cholinergic drugs improves
      symptoms in some patients with AD, but may be associated with efficacy-limiting
      adverse effects. Moreover, it is not yet known whether cholinergic drugs have the
      potential to alter the progression of AD pathology. In contrast, cumulative
      evidence from basic neuroscience and clinical research demonstrates that
      oestrogen has significant neuromodulatory and neuroprotective properties.
      Furthermore, preliminary evidence from clinical studies indicates that oestrogen
      replacement therapy can significantly enhance cognitive function in
      postmenopausal women with AD, and reduce the risk for developing the disease.
      However, long-term administration of oestrogen is associated with potentially
      serious adverse effects, including increased risk for developing malignancies of
      the uterus and the breast. Fortunately, tissue-specific analogues of oestrogen
      are in development that could specifically target the functions of the brain, and
      may be devoid of the cancer-inducing and feminising properties of the hormone.
      Availability of these analogues will make it feasible to treat AD with oestrogen
      in both women and men. However, findings of preliminary studies, although
      promising, need to be confirmed in larger, controlled clinical trials before the
      role of oestrogen in the treatment and prevention of AD can be firmly
      established.

PMID- 15991897
TI  - New drugs for tuberculosis.
AB  - In the last ten years, an unexpected resurgence of tuberculosis (TB) has occurred
      in industrialised countries; contributing factors are likely to include the
      spread of HIV infection and increasing waves of immigration. Moreover, multidrug
      resistant (MDR) strains of Mycobacterium tuberculosis are emerging, rendering
      older therapies largely ineffective. One approach to circumvent this situation
      has been the addition of antimicrobials with some in vitro antituberculosis
      activity, but which are marketed for other infections (particularly some
      quinolones and the combination of oxicillin-clavulanic acid), to current
      therapeutic regimens. New drugs, possibly acting on novel targets, are urgently
      required, as are more specific vaccines.

PMID- 15991898
TI  - Novelties in the field of fluoroquinolones.
AB  - The field of fluoroquinolone research is rapidly expanding. Bacterial targets are
      constantly changing to meet the demands of resistance. At present, new compounds
      are targeting respiratory pathogens, such as Streptococcus pneumoniae. However,
      problems such as phototoxicity, cardiotoxicity and CNS disturbances must be
      overcome. New promising fluoroquinolones include: HSR 903, LB 20304 and BAY 12
      8039. Research in the field of mycobacteria, especially for Mycobacterium
      tuberculosis, is also underway.

PMID- 15991899
TI  - Insulin lispro: a new quick-acting insulin analogue.
AB  - Insulin lispro (Humalog) is a biosynthetic insulin analogue in which the
      positions of proline and lysine are reversed in the C-terminal portion of the B
      chain. Human insulin readily self-associates into hexamers, which dissociate
      relatively slowly following subcutaneous injection. In consequence, there is a
      clinically important delay between the subcutaneous injection of soluble insulin
      and its maximal pharmacodynamic effect. The clinical development of lispro has
      been based on minor and elegant manipulation of the amino acid sequence to create
      an insulin which self associates poorly, and is therefore absorbed more rapidly
      into the circulation. By virtue of this characteristic, it has a more rapid onset
      of action than soluble insulin preparations, and a shorter duration of action.
      Potential clinical benefits include better matching of peak insulin action to
      food absorption following meals, and better glycaemic control in the immediate
      post-prandial period together with less risk of hypoglycaemia in the period
      before the next meal is due. An important practical advantage for patients is
      that the insulin injection does not have to be taken 30 min before meals, as
      recommended for soluble insulin, but can instead be given almost immediately
      before meals.

PMID- 15991900
TI  - Tirofiban: an investigational platelet glycoprotein IIb/IIIa receptor antagonist.
AB  - The deposition of a platelet rich thrombus on an atherosclerotic plaque is a
      critical step in the development of unstable coronary syndromes. Currently
      available therapeutic agents such as aspirin and ticlopidine are relatively weak
      inhibitors of platelet aggregation. Recently, antagonists to platelet
      glycoprotein IIb/IIIa (GPIIb/IIIa), a platelet surface integrin whose activation
      and subsequent binding to fibrinogen is the final common step in the formation of
      platelet aggregates, have been utilised to treat unstable angina and myocardial
      infarction. Tirofiban is a novel, specific, low molecular weight GPIIb/IIIa
      receptor antagonist, which competitively inhibits the platelet fibrinogen
      receptor. Tirofiban is administered as an intravenous infusion with a mean half
      life of 1.6 h. In healthy volunteers, the plasma concentration and half-life of
      tirofiban are unaffected by pre-treatment with aspirin, although aspirin
      increases the bleeding time prolongation caused by tirofiban. Tirofiban is
      excreted by both renal (37%) and non renal mechanisms. Three clinical trials,
      PRISM, PRISM PLUS, and RESTORE, have evaluated the safety and efficacy of
      tirofiban in unstable angina and in high-risk percutaneous transluminal coronary
      angioplasty (PTCA). When compared to heparin in the management of unstable
      angina, tirofiban decreased the odds of recurrent ischaemia, myocardial
      infarction, or death by 36% at 48 h, and death by 39% at 30 days. Similarly, the
      addition of tirofiban to heparin reduced the odds of recurrent ischaemic events
      for death at 7 days by 34%. RESTORE, a clinical trial evaluating the efficacy and
      safety of tirofiban in patients undergoing PTCA within 72 h of presentation with
      unstable angina or myocardial infarction, demonstrated a 38% reduction in a
      composite end-point at 48 h; the need for urgent PTCA and coronary artery bypass
      graft (CABG) at 30 days was reduced by 36%. Adverse side-effects, including major
      bleeding, were not significantly higher with tirofiban treatment. Tirofiban and
      other GPIIb/IIIa inhibitors represent a major advance in the treatment of
      unstable coronary syndromes and high-risk PTCA.

PMID- 15991901
TI  - Dofetilide: first of a new generation of class III agents.
AB  - Dofetilide (Pfizer, Sandwich, Kent, UK) is a novel, highly specific class III
      methanesulfonanilide anti-arrhythmic drug. At nanomolar concentrations this agent
      prolongs both the atrial and ventricular effective refractory periods and action
      potential duration. Dofetilide's mechanism of action relies on potent blockade of
      the rapidly activating, inwardly rectifying component of the delayed rectifier
      potassium current (Ikr), the main current responsible for cardiac repolarisation.
      Dofetilide does not appear to interact with other cardiac ionic channels, and
      this explains its minimal effects upon conduction velocity, myocardial
      contractility and systemic haemodynamics. Dofetilide's mechanism of action makes
      it suitable for the termination of supraventricular and ventricular
      tachyarrhythmias. Small scale clinical trials have provided encouraging results,
      with preliminary data confirming its efficacy in the termination of atrial
      fibrillation and atrial flutter, and in increasing the electrical threshold for
      inducible ventricular tachycardia/fibrillation. The results of large scale,
      randomised, placebo-controlled trials are awaited in order to establish
      dofetilide's role in clinical practice. Due to its very specific mode of action,
      dofetilide has very few systemic side-effects. Dofetilide represents a novel and
      promising new class III agent.

PMID- 15991902
TI  - The 20th International Congress of Chemotherapy.
AB  - Over 4,000 participants from all over the world attended the 20th International
      Congress of Chemotherapy (ICC) between 29th June-3rd July, 1997, in Sydney. Anti
      infective and cancer chemotherapy were discussed in a wide context, with
      presentations being made on new products, compounds in development and current
      clinical approaches. Inevitably in a congress of this size, there were many
      sessions running concurrently (usually nine), with several simultaneous poster
      sessions as well. A common theme currently at many chemotherapy congresses is the
      growth of resistance to existing agents, and the ICC was no exception. Resistance
      to Gram-positive cocci is a particular problem, and many sessions were devoted to
      this subject. This report attempts to highlight just some of the aspects of
      antibacterial chemotherapy presented at the meeting. New fluoroquinolones formed
      a major topic that attracted a number of poster sessions and symposia, continuing
      a trend seen in recent years. The streptogramins offer an alternative approach to
      combating Gram-positive infections, and a symposium was devoted to these
      compounds.

PMID- 15991903
TI  - The role of 5-HT2C receptors in affective disorders.
AB  - 5-HT(2C) receptors are predominantly localised in the brain and their
      dysregulation may contribute to particular symptoms of anxiety and depression.
      The marked affinity of several clinically established psychotropic agents sites
      (e.g., tricyclic antidepressants, clozapine, fluoxetine) for 5-HT(2C) receptor
      has generated interest in the therapeutic potential of selective, high affinity 5
      HT(2C) receptor ligands. Like the selective serotonin re-uptake inhibitor (SSRI)
      fluoxetine, high affinity selective agonists such as Ro 60-0175 and Ro 60-0332
      have potent in vivo activity in animal models suggestive of therapeutic action
      against depression, obsessive-compulsive disorder (OCD) and panic disorders. In
      contrast, 5-HT(2C) receptor antagonists such as SB-200646A or SB-221284 show
      signs of anxiolytic-like activity in tests for conditioned and phobic-like
      anxiety in rodents whereas they are inactive in tests indicative of
      antidepressant, antiOCD and antipanic activity. These results are consistent with
      an important hypothesis proposing that 5-HT has a complex, dual action on the
      neural mechanism of anxiety by either facilitating or inhibiting different kinds
      of anxiety in different brain regions. They also suggest that 5-HT(2C) receptor
      subtypes play an important role in the therapeutic properties of SSRIs. Certain 5
      HT(2C) receptor antagonists may possess negative efficacy at 5-HT(2C) receptors
      and, as inverse agonists, may control constitutive receptor activity possibly
      characterising some psychopathological states. Receptor variants exist in the
      human population and indicate possible associations between somatic mutations in
      the 5-HT(2C) receptor and psychopathology or response to drug treatment.
      Selective 5-HT(2C) receptor ligands may offer innovative and improved therapeutic
      opportunities for the biological treatment of specific aspects of psychiatric
      syndromes.

PMID- 15991904
TI  - The pursuit of precision pharmaceuticals: divergent effects of beta2 agonist
      isomers.
AB  - Beta2 agonists are the most commonly used treatment for acute
      bronchoconstriction. However, during regular use there is a progressive decline
      of protective efficacy of bronchodilators. This progressive decline has long been
      considered anomalous because with short-acting beta agonists, there is no
      corresponding change in bronchodilator efficacy. Airway hyper-responsiveness is
      itself a feature of asthma and there maybe however, there may be an increase in
      airway hyper-responsiveness following regular use of beta2 agonist. Airway
      hyperresponsiveness could diminish the capacity of beta agonists to protect from
      or result in paradoxical bronchospasm and there effects of racemic salbutamol.
      There have been reports of increased morbidity and mortality associated with
      excessive use of beta(2) agonists. As all beta agonists used clinically are
      racemates composed of 1:1 mixtures of R and S isomers, conducted on the possible
      involvement of the isomers in hyper-responsiveness. Hyper-responsiveness cannot
      be attributed to the R isomer, whose capacity to activate beta adrenoceptors will
      nullify this effect. In contrast, extensive evidence indicated that the S isomer
      might cause hyper-responsiveness and potential airway inflammation. Further, the
      S isomer shows a propensity to activate human eosinophils and alter muscarinic
      M(2) receptor functions. The S isomer, which makes no contribution to therapeutic
      efficacy and may exacerbate asthma, might therefore be excluded from asthma
      therapy.

PMID- 15991905
TI  - Dendritic cell-based approaches to cancer immunotherapy.
AB  - Immunologic approaches to the treatment of malignancies are currently enjoying a
      resurgence of enthusiasm due to the discovery of tumour-associated antigens and
      the requirements for stimulating a tumour antigen-specific immune response. The
      goal of the newer strategies is to stimulate immunity against specific tumour
      associated antigens, rather than to broadly, but non-specifically, stimulate the
      immune system. Since dendritic cells, professional antigen-presenting cells, play
      a central role in stimulating immune responses in vivo, there is considerable
      interest in immunising patients with autologous dendritic cells loaded with
      tumour antigens of interest. Methods for generating large numbers of dendritic
      cells under clinically-applicable conditions have been developed and it has been
      shown that they may be loaded with antigen in many different forms including
      proteins or peptides, RNA or DNA and cellular extracts. Ongoing research is
      seeking to optimise the purity, antigen loading and maturation of the dendritic
      cells. Phase I clinical trials have been initiated in order to study the safety
      and feasibility of immunisations with dendritic cells in humans with various
      malignancies. Phase II studies will be performed to establish which tumours and
      clinical scenarios will be most relevant for dendritic cell immunotherapy.
      Although the commercial applicability of dendritic cell-based immunotherapy has
      been recognised by the biotechnology industry, commercial availability of
      dendritic cell vaccines await phase III studies.

PMID- 15991906
TI  - Anti-angiogenic therapies in cancer clinical trials.
AB  - Strategies involving vasculature have widely been acknowledged to have
      therapeutic potential in the management of cancer and other diseases. Based on a
      large body of evidence from preclinical studies and early clinical trials there
      is considerable optimism that anti-angiogenesis and vascular targeting will be a
      major clinical therapy. This review considers some 30 anti-angiogenic and
      vascular targeting agents that are currently in cancer clinical trials and
      highlights specific problems relating to the assessment of the activity of these
      agents in patients, trial design, potential toxicities and resistance mechanisms.

PMID- 15991907
TI  - Novel approaches for the induction of T helper 1 (Th1)- or Th2-type mucosal and
      parenteral immune responses.
AB  - Mucosal surfaces are constantly challenged by micro-organisms and are protected
      by an integrated component of the immune system called mucosa-associated
      lymphoreticular tissue (MALT). The immune responses elicited at the mucosal level
      are regulated by T-helper (Th) cells and involve secretory IgA (S-IgA) antibodies
      (Abs) and cytotoxic T-lymphocytes (CTLs). Mucosal immunisation has the advantage
      over parenteral immunisation, of inducing S-IgA Abs and of conferring protection
      at both the mucosal and parenteral levels; however, administration of soluble
      antigens through a mucosal route very seldom results in significant mucosal and
      systemic immune responses. Therefore, appropriate mucosal adjuvants, recombinant
      bacterial and viral vectors and delivery systems have been developed to increase
      the immunogenicity of vaccine antigens and to preferentially induce antigen
      specific T-helper (Th)1- or Th2-type responses, which in turn result in polarised
      effector immune responses. Understanding the mechanisms underlying Th1- and Th2
      type developmental pathways and the ability of novel mucosal adjuvants and
      delivery systems to target the desired Th1- or Th2-type immune response would
      help to design effective mucosal vaccines, inducing predominant cell-mediated or
      humoral responses.

PMID- 15991908
TI  - The role of cytokines in unstable angina.
AB  - A growing body of evidence suggests that inflammation plays a major role in the
      pathogenesis of unstable angina; this evidence is mainly derived from the
      prognostic role of the acute phase reaction proteins, such as C-reactive protein
      (CRP) and fibrinogen. Since the production of acute phase protein is under the
      control of the pro-inflammatory cytokines, it is probable that citokines, such as
      tumour-necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6 are involved in
      the same process. Indeed, elevated levels of IL-1 and IL-6 have been found by our
      group and by others, in patients with acute coronary syndromes. Cytokines may
      have procoagulant effects, directly or via endothelial dysfunction, and may
      induce plaque vulnerability or rupture. They may also be responsible for the
      activation of other cells, as neutrophils or mast-cells. Although it is
      conceivable that activated lymphocytes, via interferon-gamma production, are
      responsible for macrophage activation and cytokine production in unstable angina,
      the trigger and the precise mechanism of this event are still unknown. The
      multiple roles of cytokines in unstable angina suggest that a targeted anti
      inflammatory therapy might be a novel approach in the future for the treatment of
      this syndrome.

PMID- 15991909
TI  - Gene therapy for lysosomal storage diseases.
AB  - The lysosomal storage diseases are a family of inherited disorders usually caused
      by a deficiency in a single lysosomal enzyme, and are characterised by
      progressive intralysosomal storage in multiple cell types. Although individual
      syndromes can be uncommon, as a whole this family of diseases affects
      approximately 1 in 3,000 live births. The severity of disease can be variable,
      ranging from minimal evidence of lysosomal storage to widespread multi-system
      involvement and early mortality. Although the enzymatic defects responsible for
      most of these diseases are known, treatment options for the majority of these
      disorders are limited to supportive care and genetic counselling. Knowledge of
      the genetic defects underlying these diseases, coupled with advances in the
      fields of gene transfer and expression, provide an opportunity to utilise gene
      therapy strategies in order to treat these disorders. Here we provide a
      description of the biochemical and molecular basis of gene therapy for lysosomal
      storage diseases, as well as an overview of some of the in vitro and in vivo
      studies that have been performed.

PMID- 15991910
TI  - Transgenic animals as drug factories: a new source of recombinant protein
      therapeutics.
AB  - The utility of transgenic animal bioreactors for the production of complex
      therapeutic proteins is based on lower production costs, higher production
      capacities and safer, pathogen free products. Until gene therapy becomes broadly
      efficacious, transgenic-derived therapeutics are the most attractive alternative
      for prophylactic, replacement therapy in genetic disorders, such as haemophilia.
      Many other disease states need short-term treatment of significant amounts of
      recombinant proteins that could be made amply available from transgenic animal
      sources. In addition, transgenic animals will provide an ideal expression system
      for the production of a portfolio of alternative therapeutics for patient
      populations developing inhibiting antibodies, for enhanced bioactivity, or for
      increased plasma clearance times. The FDA approval of a transgenic-derived
      therapeutic is still pending, but a review of Phase I & II data from antithrombin
      III from goat milk is encouraging, and companies are continuing to add potential
      therapeutics to their product pipeline.

PMID- 15991911
TI  - Duloxetine (LY 248686): an inhibitor of serotonin and noradrenaline uptake and an
      antidepressant drug candidate.
AB  - Duloxetine is a potent inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and
      noradrenaline (NE) uptake in vitro and in vivo and is 3- to 5-times more
      effective at inhibiting 5-HT uptake. Duloxetine is a weak inhibitor of dopamine
      (DA) uptake and the binding of radioligands to neurotransmitter receptors. Upon
      administration of duloxetine in vivo, the inhibitory effects on uptake of 5-HT
      and NE persist for up to 8 h. Desmethylduloxetine, a potential metabolite, is
      also an inhibitor of 5-HT and NE uptake. Consistent with the ability to inhibit
      the uptake of 5-HT, duloxetine blocks p-chloroamphetamine induced depletion of
      mouse and rat brain 5-HT. Duloxetine also blocks the 6-hydroxydopamine induced
      depletion of mouse heart NE and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) induced depletion of NE in frontal cortex but does not block the MPTP
      induced depletion of DA in rat striatum. Electrophysiological studies show that
      duloxetine decreases the activity of 5-HT neurones in dorsal raphe and at a 5
      times higher dose also decreases the activity of NE neurones in the locus
      coeruleus. Microdialysis techniques have demonstrated that duloxetine effectively
      elevates extracellular 5-HT and NE levels in rat frontal cortex and hypothalamus.
      Antagonists at somatodendritic 5-HT(1A) autoreceptors or at presynaptic alpha(2)
      adrenergic receptors could augment the duloxetine induced elevation of
      extracellular 5-HT, NE and DA levels. Duloxetine produces behavioural responses
      consistent with the enhancement of 5-HT and NE neurotransmission. Pharmacokinetic
      studies in healthy human volunteers show that duloxetine has a half-life of 10 -
      15 h without the influence of food. In preliminary clinical trials, duloxetine
      has shown antidepressive effects in patients with major depression. Duloxetine
      offers an opportunity to utilise combined central 5-HT and NE neuronal pathways
      to improve the treatment of patients with major depression.

PMID- 15991912
TI  - Abciximab (Reopro): a clinically effective glycoprotein IIb/IIIa receptor
      blocker.
AB  - Acute coronary syndromes are responsible for the deaths of tens of thousands of
      patients every year. Rupture of coronary atheromatous plaques with resultant
      luminal thrombosis is the cause in most cases. Although great steps forward have
      been taken in the management of acute myocardial infarction (MI) and unstable
      angina (UA), new therapeutic strategies are required to reduce further the
      incidence and risk of these events. At present, aspirin, nitrates and heparin are
      the conventional treatments for unstable angina. Aspirin, in combination with a
      thrombolytic agent or with percutaneous transluminal coronary angioplasty (PTCA),
      has been shown to be effective in reducing mortality in acute MI. Heparin is
      conventionally used in all PTCA procedures, whereas its efficacy in enhancing the
      therapeutic role of thrombolytic agents remains uncertain and may depend on the
      thrombolytic agent used. PTCA, which is also an effective therapy for stable
      angina, can be complicated by intimal dissection and thrombosis in a minority of
      cases, with vessel restenosis leading to recurrent symptoms in approximately 30%
      of cases. A number of new agents are being evaluated in both acute coronary
      syndromes and PTCA. These can be classified as adenosine diphosphate (ADP)
      receptor antagonists, Factor Xa inhibitors (low-molecular weight heparin [LMWH],
      direct thrombin inhibitors, new thrombolytic agents and glycoprotein IIb/IIIa
      receptor blockers. Of the latter, the most studied is abciximab, the Fab fragment
      of the chimeric monoclonal antibody, 7E3. This is a potent inhibitor of platelet
      aggregation. Four major clinical studies of PTCA in high-risk patients have
      demonstrated clear efficacy of abciximab in reducing acute ischaemic
      complications, mainly by reducing the frequency of MI and the need for repeat
      revascularisation. Unlike other glycoprotein IIb/IIIa receptor blockers, both
      short- and long-term efficacy have been demonstrated. Its impact on the rate of
      restenosis after PTCA is unclear. Abciximab's role in an era of intracoronary
      stent implantation is undergoing further study (with encouraging early results).
      Its role in other situations, such as the early (non-angioplasty) management of
      unstable angina and its ability to enhance the efficacy of thrombolytic agents,
      is under active investigation.

PMID- 15991913
TI  - The 1st annual meeting of the American Society of Gene Therapy.
AB  - The inaugural meeting of the American Society of Gene Therapy (ASGT) attracted
      over 1700 participants to the Pacific gateway city of Seattle, Washington for a
      multifaceted 4 day meeting organised into a series of symposia, workshops, poster
      sessions and educational opportunities representative of gene therapy's immense
      diversity. Presentations from the international assemblage of industrial and
      academic scientists covered a blend of data from cutting edge research to current
      clinical investigations across a spectrum of therapeutic targets. Unique
      educational sessions allowed participants to gain basic information regarding
      areas of gene therapy research in which they lacked familiarity, whereas several
      'Meet the Investigator' sessions allowed participants to interact directly with
      experts in small group settings in order to obtain a more sophisticated
      perspective through informal dialogue. A large majority of the symposia and
      poster presentations showcased the development and current successes of viral
      mediated gene therapy although non-viral approaches received their share of
      attention. Despite the fact that promising results were presented from ongoing
      clinical trials using viral-mediated gene therapy, much of the symposia addressed
      the accompanying problems of immunogenicity, low levels of gene expression and
      lack of control of gene expression that are presently limiting the clinical
      success of virally mediated gene transfer.

PMID- 15991914
TI  - Topoisomerase targeted agents - chemistry to chemotherapy.
AB  - This meeting demonstrated the extent of new knowledge on the interaction of
      topoisomerase enzymes with DNA at the molecular level, including their high level
      of sequence recognition and their efficient DNA cleavage and religation
      mechanisms. Speakers discussed the use of this new knowledge to create detailed
      models of enzyme/DNA/drug ternary complexes, and to design more efficient enzyme
      inhibitors. Other factors needed to turn an efficient inhibitor into a useful
      drug were also reported on; these included selectivity, distribution, metabolism,
      macromolecular binding, scheduling and toxicity profiles.

PMID- 15991915
TI  - Chemokine receptor antagonists: novel therapeutics for inflammation and AIDS.
AB  - To date almost 40 human chemokines have been described, modulating a complex and
      overlapping set of biological activities important for basal leukocyte
      trafficking, as well as the extravasation and tissue infiltration of leukocytes
      in response to inciting agents. Chemokines appear to be key mediators in a number
      of inflammatory pathologies as a result of their chemotactic effects on almost
      every leukocyte type, including neutrophils, eosinophils, basophils, monocytes,
      dendritic cells, NK cells, B-cells and T-cells, together with their ability to
      stimulate effector functions, such as granule release and superoxide radical
      production from these cells. With the recent discovery that some chemokine
      receptors function as HIV-1 co-receptors and with accumulating evidence that
      chemokines may also regulate certain aspects of haematopoiesis, angiogenesis and
      apoptosis, the chemokines and their receptors have emerged as a new set of drug
      discovery targets for the pharmaceutical and biotechnology industry.

PMID- 15991916
TI  - The link between inflammatory disease and patterns of leukocyte recruitment.
AB  - Leukocytes participate in different ways in inflammatory diseases. The nature of
      the disease can be seen as a reflection, in part, of the migration patterns of
      different leukocyte types in asthma versus inflammatory bowel disease (IBD). The
      molecular basis that underlies the selective recruitment of distinct leukocytes
      to unique microenvironments is a result of the interplay of selectins, integrins
      and chemoattractants. The ability to understand and dissect these pathways in
      disease processes will be an important tool for the development of novel
      therapeutics with highly effective suppressive potential and greatly reduced side
      effects.

PMID- 15991917
TI  - Drug therapy for ocular allergy.
AB  - The spectrum of ocular allergy ranges from mild, non-sight threatening disease,
      such as hay fever, to disorders such as atopic keratoconjunctivitis (AKC) which
      cause permanent ocular surface changes and reduced vision. The ideal treatment is
      with topical preparations. Launched topical preparations include anti-histamines
      and mast cell (MC) stabilisers, which are safe, but only moderately potent,
      steroids, which are very potent, but carry very serious side-effects, and
      cyclosporin A, which is not widely available and difficult to tolerate. There are
      a number of anti-histamines, MC stabilisers (and combinations thereof) and
      steroids in development which are of potential interest. Other possibilities for
      therapeutic intervention include inhibition of tryptase, cyclooxygenase (COX),
      leukotrienes (LTs), bradykinins (BKs), platelet activating factor (PAF) and
      immunoglobulin E (IgE). Therapies based on cytokine antagonism and agonism, T
      cell inhibition and adhesion molecule antagonism might be expected to provide
      safe, but potent new modes of treatment. The increasing interest in research into
      the pathogenesis of ocular allergic inflammation may lead to more relevant
      approaches, such as eosinophil inhibition. Success will be highly dependent on
      the ability to produce suitable topical ophthalmic preparations.

PMID- 15991918
TI  - Immunomodulatory aspects of photodynamic therapy.
AB  - In its conventional form, photodynamic therapy (PDT) is a clinically effective
      technique with which to treat tumours accessible to visible light. PDT utilises
      light absorbing compounds which catalyse the generation of toxic oxygen species,
      to produce localised antitumour effects. It has become apparent over the past
      decade that PDT also exhibits immunomodulatory attributes. Experimental animals
      may possess heightened antitumour immunity after tumour ablation with PDT. In
      contrast, at sub-phototoxic levels of photosensitiser, in combination with whole
      body light irradiation, PDT lessened disease severity when applied in different
      models of autoimmunity. Although the behaviour of lymphocytes may be affected by
      treatment, the ability of PDT to down-regulate autoimmune processes appears to be
      related to its capacity to influence the immunostimulatory attributes of antigen
      presenting cells.

PMID- 15991919
TI  - Inducible nitric oxide synthase and inflammation.
AB  - Nitric oxide (NO), derived from L-arginine (L-Arg) by the enzyme nitric oxide
      synthase (NOS), is involved in acute and chronic inflammatory events. In view of
      the complexity associated with the inflammatory response, the dissection of
      possible mechanisms by which NO modulates this response will be profitable in
      designing novel and more efficacious NOS inhibitors. In this review we describe
      the consequences associated with the induction of inducible nitric oxide synthase
      (iNOS) and its therapeutic implications.

PMID- 15991920
TI  - The therapeutic effects of vitamin D3 and its analogues in psoriasis.
AB  - Psoriasis is a common skin disease which is characterised by the proliferation
      and abnormal differentiation of keratinocytes, coupled with complex immune
      disturbances. The beneficial effects of vitamin D derivatives in this disease are
      due to their capacity to inhibit proliferation, their ability to induce normal
      differentiation and their immunomodulatory properties. Since the systemic
      administration of these compounds is limited by their effect on calcium
      metabolism, topical preparations have become available in most countries. Topical
      calcipotriol and/or tacalcitol are now considered as first-line treatment for
      mild-to-moderate psoriasis and can be taken in combination with other systemic
      therapies in more severe cases of the disease. Novel orally active vitamin D
      analogues, with minimal calcitropic effercts, are, however, required for more
      effective treatment.

PMID- 15991921
TI  - Emerging concepts in cardiovascular disease: should elevated serum uric acid be
      considered a risk factor?
AB  - Uric acid is the final breakdown product of purine metabolism in man. There is a
      growing body of evidence that indicates that elevated uric acid levels increase
      the probability of developing hypertension and cardiovascular disease. The
      frequency of hyperuricaemia in untreated hypertensive individuals ranges from 25 
      50%. Furthermore, elevated serum uric acid has been reported to increase the
      probability of developing hypertension by 87% and to increase the mortality rate
      from ischaemic heart disease. Several studies have reported that changes in serum
      cholesterol parallel changes in serum uric acid in both order and magnitude. Most
      recently, hyperuricaemia has been added to the constellation of abnormalities
      that comprise Syndrome X. The pathophysiology of hyperuricaemia and the link
      between hyperuricaemia, hypertension and cardiovascular disease are poorly
      understood. It is entirely possible that hyperuricaemia is part of a pathologic
      process that underlies fundamental alterations in renal function, as well as
      other metabolic pathophysiologies that ultimately lead to hypertension and
      cardiovascular disease.

PMID- 15991922
TI  - Ongoing planned clinical trials investigating the pulmonary management of cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is a genetic disease where abnormalities in ion transport
      lead to poor clearance of viscoelastic secretions and a susceptibility to
      bacterial colonisation. Once established the infection/inflammatory cascade
      appears to be self-perpetuating. Treatment is therefore based on a number of
      strategies. Recently, advances have been concentrated at correcting the gene
      defect. Other strategies include correction of the ion transport defect. These
      may be crucial in patients if started before there is significant pulmonary
      disease. Developments aimed at improving the rheological properties of
      secretions, controlling airway infection and inflammation are essential once
      bronchopulmonary sepsis is established. This report looks at some of the clinical
      trials that are ongoing or planned in the treatment of pulmonary disease in CF.

PMID- 15991923
TI  - Modafinil: a novel stimulant for the treatment of narcolepsy.
AB  - Excessive daytime sleepiness (EDS) is a common and debilitating symptom of
      narcolepsy and other sleep disorders. Modafinil is a novel stimulant which
      effectively treats EDS, yet lacks many of the undesirable side-effects commonly
      encountered with currently available compounds. The specific mode of action of
      modafinil is not well understood, but it may promote sleep by indirectly
      influencing adrenergic or GABAergic neurotransmission. Modafinil-induced
      wakefulness is not associated with rebound hypersomnolence or the potential for
      abuse as is often encountered with other stimulants such as amphetamines. At
      typical therapeutic doses, modafinil may produce dry mouth but generally has a
      low incidence of minor side-effects. Many preclinical and clinical studies have
      demonstrated the effectiveness of modafinil in promoting wakefulness and
      vigilance in normal subjects and in those with EDS. Modafinil significantly
      improves the EDS of narcolepsy and also may improve the EDS of idiopathic
      hypersomnia and obstructive sleep apnoea. Modafinil's low prevalence of side
      effects, minimal potential for abuse, and lack of rebound hypersomnia indicate
      that it has potential to become a widely prescribed drug for the treatment of
      narcolepsy.

PMID- 15991924
TI  - Pasteur Euroconference on future therapies for an anxious world.
AB  - The aim of this meeting was to explore the molecular targets for tomorrow's drugs
      with a group of European and North American speakers from the pharmaceutical
      industry and academia presenting both data and ideas. Several speakers considered
      5-hydroxytryptamine(1B/D) (5-HT(1B/D)) receptor antagonists to be a promising
      target for the treatment of obsessive compulsive disorders (OCD). 5-HT moduline,
      a peptide modulator of the 5-HT(1B/D) receptor, presents a potentially subtle way
      of intervention. No clinical data are as yet available on 5-HT(1B/D) receptor
      antagonists. The paradox of agonists, partial agonists and antagonists at the 5
      HT(1A) receptor (all having anxiolytic activity in animal models) was discussed.
      Although the 5-HT(1A) agonists tested in clinical trials to date have been
      disappointing, the clinical potential of 5-HT(1A) antagonists still has to be
      evaluated. Similarly, both agonists and antagonists at the 5-HT(2C) receptor have
      been shown to be active in animal models of anxiety. It seems, however, that 5
      HT(2C) agonists may have a therapeutic potential in panic disorders and OCD,
      while the antagonists may be more appropriate in generalised anxiety.
      Cholecystokinin (CCK) has been shown to be implicated in panic attacks which can
      be induced by agonists at the CCK-B subtype. CCK-B antagonists are thus potential
      antipanic agents although this has not yet been confirmed by clinical trials.
      Finally, inhibition of glutamatergic neurotransmission produces anxiolytic
      effects in a wide-range of animal models and the new antagonists at the
      metabotropic glutamate receptors may have potential as anti-anxiety agents. This
      report focuses on the presentations that addressed novel drug candidates or
      potential new drug targets.

PMID- 15991925
TI  - 70th Scientific Sessions of the American Heart Association.
AB  - The 70th Scientific Sessions of the American Heart Association were attended by
      37,000 people, including 21,000 medical professionals. Out of 13,103 submissions,
      4,300 abstracts were selected for presentation at this conference. The abstracts
      have been published in a supplement to Circulation (Volume 96, Number 8).

PMID- 15991926
TI  - IBC's 4th Annual Conference on Signal Transduction Therapy: novel targets for
      therapeutic intervention.
AB  - A variety of approaches to investigate cell signalling were presented. The main
      goal of the speakers was to make use of signalling pathways as targets for the
      development of new drugs. These targets included protein kinase A anchoring, Ras
      dependent transformation, growth factor receptor tyrosine kinases (trk and
      insulin), cytokine-mediated signalling, phospholipid lipases and
      immunosuppressant targeted enzymes. Each of the speakers gave a concise summary
      of the area involved and the rationale supporting their approaches to
      investigation.

PMID- 15991927
TI  - Endothelin and erectile dysfunction: a target for pharmacological intervention?
AB  - Although erectile dysfunction (ED) is not life threatening, this common problem
      can significantly affect the quality of life and psychological and social well
      being. The Massachusetts male ageing study (1,290 men aged 40 - 70 years) showed
      that 52% of men reported some degree of ED (17.1% mild, 25.2% moderate, 9.6%
      total). In the UK, an estimated 17 - 19% of men are thought to suffer from ED.
      This problem is more common with advancing age and since this proportion of the
      population is increasing, the prevalence of ED is expected to rise. Endothelin-1
      (ET-1) belongs to a family of potent vasoconstrictor peptides consisting of 21
      amino acids. We review the evidence showing that ET-1 plays a role via (ET(A) and
      ET(B) receptors) in the regulation of cavernosal smooth muscle tone. We also
      consider the various risk factors that are involved in the pathogenesis of ED and
      how these relate to the action of ET-1. In particular, the role of diabetes,
      hypertension, smoking and dyslipidaemia are discussed. The pharmaceutical
      industry has declared an interest in the development of ET antagonists for use in
      the treatment of various diseases including ED. We briefly comment on
      experimental ET-1 antagonists that may be of therapeutic benefit in ED.

PMID- 15991928
TI  - Molecular mechanisms underlying the role of nitric oxide in the cardiovascular
      system.
AB  - In the cardiovascular system, nitric oxide (NO) is involved in the short and long
      term regulation of haemodynamics, and in a number of their pathological
      alterations. Investigation into the biochemistry of NO-synthase isoforms has
      confirmed that they also all produce superoxide anion (O(*)). The free radical NO
      can interact with many targets on which novel information has been recently
      obtained. The major results of these interactions are not only the well known
      activation of guanylyl cyclase, but also the formation of potentially cytotoxic
      peroxynitrite (ONOO(-)), and the formation of S-nitrosothiols and non-haem iron
      dinitrosyl dithiolate complexes. Tissue O(2), O(*), low molecular weight thiols
      and transition metals (especially FeII) play a pivotal role in directing NO
      towards targets responsible for biological effects, or storage or release from
      these stores. In addition, circulating forms of NO have been proposed with S
      nitrosation of blood proteins. All these mechanisms provide potential
      pharmacological targets for future therapeutic strategies.

PMID- 15991929
TI  - Antihypertensive drugs interacting with central imidazoline (I1)-receptors.
AB  - Central imidazoline (I(1))-receptors have been recognised as targets of a new
      class of centrally acting antihypertensives. The stimulation of these I(1)
      receptors induces peripheral sympatho-inhibition and a reduction of (elevated)
      blood pressure. Moxonidine and rilmenidine are the prototypes of this new class
      of centrally acting antihypertensives. These imidazoline receptor stimulants are
      effective antihypertensives with a haemodynamic profile which is attractive from
      a pathophysiological point of view. Since both moxonidine and rilmenidine have a
      much weaker affinity for central (2)-adrenoceptors than classic centrally acting
      drugs, for example, clonidine and alpha-methyl-DOPA, the side-effects profile of
      the I(1)-receptor stimulants is significantly better. The imidazoline (I(1))
      receptor stimulants are the subject of the current survey. They appear to offer
      the possibility of developing centrally acting antihypertensives with the same
      attractive haemodynamic characteristics as the classic alpha(2)-adrenoceptor
      stimulants, but with clearly better tolerability. Their potential use in the
      treatment of congestive heart failure and the metabolic syndrome is subject to
      clinical investigation.

PMID- 15991930
TI  - The prospects of hepatic drug delivery and gene therapy.
AB  - Liver targeted therapy is designed to deliver a substance preferentially to the
      organ in order to increase the accumulation, improve the therapeutic effect and
      reduce toxicity to other organs. The aim of selective targeting is to deliver a
      substance to a specific cell type in the liver. A variety of vehicles have been
      designed and further modified for selective targeting of therapeutics to the
      liver. The targeting properties and strategies of commonly used agents, such as
      liposomes, microspheres and recombinant chylomicrons, are discussed. Viral and
      non-viral vectors, such as cationic liposomes, reconstituted chylomicron
      remnants, adenoviruses, adeno-associated viruses, retroviruses, and SV-40, are
      currently being evaluated for the delivery of DNA to the liver. New developments
      in improving the targeting efficiency of the available vectors while avoiding
      their disadvantages have made their use in clinical trials of various genetic
      disorders possible. For viral hepatitis, antisense and ribozyme techniques are
      being employed with selective targeting approaches. A commonly employed current
      strategy for targeting hepatocellular carcinoma cells is to make the tumour cells
      convert non-toxic 'prodrugs' to toxic metabolites in situ, achieving a high
      concentration of the toxic product in the local milieu, while avoiding systemic
      toxicity. Although gene therapy itself is in its infancy, some encouraging
      results have been developed in studies of familial hypercholesterolaemia,
      haemophilia, alpha1-antitrypsin deficiency and Crigler-Najjar syndrome. The
      potential strengths as well as the problems with these studies are discussed.

PMID- 15991931
TI  - The prospects for in utero stem cell transplantation.
AB  - In utero transplantation of haematopoietic stem cells into the foetus, early in
      gestation, offers a new approach to genetic disorders. Immunological naivete and
      the sterile uterine environment are perfect conditions for transplantation, so
      that even mismatched cells will engraft. There have been notable successes world
      wide, although numbers are small, which gives encouragement to further work
      directed at means to enhance and sustain engraftment in a foetal recipient. For
      example, stem cells for transplant can be obtained from various sources but these
      have different properties that can be exploited for therapy in specific
      disorders. However, some disorders may not be amenable to in utero
      transplantation and there is need to achieve consensus in order to ensure that
      the procedure is used appropriately, for the benefit of all.

PMID- 15991932
TI  - AntiTNF-alpha agents in the treatment of inflammation.
AB  - Tumour necrosis factor/cachecin (TNF-alpha) and lymphotoxin (LTalpha / TNF
      alpha), 2 members of the TNF family of cytokines, have numerous biological
      functions, such as induction of apoptosis, cytotoxicity, inflammation,
      immunoregulation, proliferation and antiviral responses. Although TNF-alpha is
      produced by many cell types, the majority comes from activated macrophages. The
      related molecule, LT-alpha is produced mainly by activated lymphocytes and shares
      many of TNF's properties. TNF-alpha is active in both of its molecular forms, a
      secreted 17 kDa mature form and a transmembrane 26 kDa precursor. It induces
      activity by stimulating 2 distinct receptor subtypes, TNFR1 (55 kDa) and TNFR2
      (75 kDa). The activation of TNFR1 is generally thought to trigger the majority of
      inflammatory and apoptotic effects, although TNFR2 has recently been shown to
      play more of a role in signal transduction than was initially thought. TNF-alpha
      is responsible for the induction of apoptosis in certain cell types, where it
      plays a pivotal role in the induction of cytotoxicity, killing of neoplastic
      cells and deletion of autoreactive T-cell clones. This cytokine, and in
      particular, its overproduction, has been implicated in the pathogenesis of a
      variety of immunologically mediated inflammatory diseases, including endotoxic
      shock, inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid
      arthritis (RA). Currently, there is an intense effort underway to regulate TNF
      alpha production and activity, in order to treat diseases where TNF-alpha is
      thought to be pathologically indicated. To achieve this goal, the pharmaceutical
      industry is currently pursuing a 2 pronged strategy: a) testing biological agents
      such as antibodies against TNF-alpha or soluble TNF-alpha receptor constructs,
      and b) identifying small molecular inhibitors directed against targets such as
      phosphodiesterase-IV (PDE-IV) and TNF-alpha converting enzyme (TACE), a subgroup
      of the matrix metalloproteinases (MMP). The main difficulties in the clinical
      implementation of the biological agents are: development of immunogenicity, lack
      of oral availability and the high cost of production. The currently available
      small molecular compounds exhibit poor bio-availability and low selectivity,
      resulting in unacceptable side effects and a low therapeutic index. Despite these
      hurdles, numerous companies are actively pursuing agents that inhibit TNF-alpha.

PMID- 15991933
TI  - Do antivirals have any utility in the treatment of arthritis?
AB  - Viruses have been linked to arthritides by several pathways. Apart from the
      ability of different viral pathogens to cause arthritic symptoms directly, only
      some circumstantial evidence for the involvement of (retro)viruses in the
      pathogenesis of rheumatoid arthritis has been presented in recent years.
      Therefore, the question of whether antiviral agents can be used to treat
      arthritis has become of interest. However, the mechanisms by which exogenous
      retroviral infection as well as activation of endogenous retroviral sequences may
      potentially lead to the induction of rheumatoid arthritis is just beginning to
      emerge. Moreover, the hypothesis that persistent viral infection may account for
      some hitherto unclassified, chronic arthritides, still needs to be confirmed.
      Therefore, the use of antiviral agents in the treatment of arthritides has been
      limited to viral complications of anti-arthritic therapy and to some experimental
      approaches. In this review, we will focus on current concepts of viral
      involvement in arthritis and point to future directions in the use of antiviral
      agents for arthritis.

PMID- 15991934
TI  - Drug targeting systems for cancer chemotherapy.
AB  - Tumour specific drug targeting has been a very actively investigated area for
      over 2 decades. Various approaches have involved the use of drug delivery systems
      that can localise the anticancer agent at the tumour site without damaging the
      normal cells. For this purpose, various delivery systems that have been utilised
      are liposomes, microspheres and recently, nanoparticles. Two liposome
      formulations containing anticancer drugs for example, adriamycin and daunomycin
      are already on the market in the USA and Europe. Microspheres are also being
      investigated for delivering various anticancer drugs and protein/peptides for
      anticancer treatment, and several formulations are in Phase I/II clinical trials.
      Antitumour drugs have also been linked to tumour specific monoclonal antibodies
      via various chemical linkages. Doxorubicin was linked to a chimeric monoclonal
      antibody that was targeted to the Lewis Y antigen. Though this conjugate
      initially showed potential, it was recently dropped from Phase II clinical
      trials. Another approach with monoclonal antibodies has been the use of
      immunotoxins. Immunotoxins initially showed promise as potential anticancer
      agents at picomolar concentrations but several clinical and preclinical studies
      have not shown much promise in this regard. Drug containing liposomes and
      microspheres have been further linked to tumour specific monoclonal antibodies to
      enhance their tumour specificity. Most of the studies with immunoliposomes or
      targeted microspheres have not gone beyond the preclinical studies. New
      therapeutic approaches are presently emerging based on natural products like
      cytokines, peptide growth factor antagonists, antisense oligonucleotides and
      specific genes. These approaches need the help of delivery systems to deliver
      these complex molecules to tumour cells. One of the current pursued approaches is
      the use of cationic liposomes. Several clinical studies are undergoing with
      various cationic liposomes and the next few years will demonstrate the usefulness
      of this approach. In recent years, the problems in cancer treatment have been
      complicated with the emergence of resistance strains leading to resistant and
      cross-resistant tumour cells. Several agents have been used to overcome or
      reverse drug-resistance in solid tumours and it remains a highly pursued area in
      cancer treatment.

PMID- 15991935
TI  - Mucin based breast cancer vaccines.
AB  - Of the 8 human epithelial mucins identified so far, MUC1 has been the focus of
      attention for immunotherapeutic applications. The gene MUC1 encodes a large
      membrane associated glycoprotein where the majority of the extracellular domain
      is made up of tandem repeats of 20 amino acids. In breast cancer MUC1 is up
      regulated and as a result of changes in glycosyl transferases, the complex
      carbohydrate side-chains are shortened leading to the exposure of novel peptide
      and carbohydrate epitopes. Cellular and humoral immune responses to MUC1 have
      been documented in benign and malignant breast disease and in some circumstances,
      T-cell responses to MUC1 may not depend on presentation by the major
      histocompatibility complex. Several immunogens based on MUC1 are being
      investigated for the immunotherapy of breast cancer in model systems and in the
      clinic. These include cell lines that express MUC1, either given alone or fused
      with professional antigen presenting cells. Approaches that may prove more
      feasible in the clinic include the use of peptide epitopes, usually from the
      tandem repeat of the extracellular domain, given either with conventional
      immunological adjuvants or coupled to mannan (a polysaccharide also known as
      polymannose), which may target uptake of peptide into antigen presenting cells.
      Cellular and humoral immune responses to these immunogens have been noted in
      patients with advanced malignancy. Targeting of peptide epitopes may also be
      achieved using antibodies to MUC1 through the idiotype network. Use of antibodies
      to MUC1 has been associated with a survival benefit for patients with ovarian
      cancer, but prospective studies are awaited. The use of cDNA encoding MUC1 may
      allow endogenous processing of antigen and thus augment immunogenicity. Phase I
      studies using the vaccinia virus as a vector have been completed and Phase II
      studies have begun. Studies examining the potential role of carbohydrate antigens
      have suggested that the ability to generate a specific immune response may
      influence survival of patients with metastatic epithelial malignancies. Again,
      these findings will be tested in the Phase III setting. While examining the
      potential role of immunogens based on MUC1, it is also necessary to understand
      the nature of immunosuppression in patients with advanced malignancy in order to
      develop strategies to enhance the immunogenicity of potential cancer vaccines.

PMID- 15991936
TI  - c-erbB-2 as a target for immunotherapy.
AB  - The c-erbB-2 proto-oncogene encodes a 185 kDa transmembrane Type 1 tyrosine
      kinase receptor whose amplification and/or overexpression has been linked with
      poor prognosis in a variety of cancers. The oncoprotein has been suggested to
      play a key role in tumour cell invasion, motility and metastasis, and in
      responsiveness to therapeutic agents. Over-expression of c-erbB-2 therefore
      identifies an important subset of patients with a high probability of relapse,
      but low probability of response to certain conventional therapies. The cell
      surface location of the oncoprotein, its stability of expression and low levels
      in normal adult tissues render it an attractive target for immunotherapeutic
      intervention. Although a 'self' antigen, there is evidence that c-erbB-2 p185 can
      induce both humoral and cell-mediated immune responses in cancer patients.
      Approaches to exploit p185 as an immunotherapeutic target include vaccination
      with peptides, plasmid DNA or vectors (viruses/bacteria) carrying the gene; with
      cytokines, co-stimulatory factors and superantigens being evaluated as adjuvants.
      Many monoclonal antibody (mAb)-based strategies are also in clinical development.
      Monoclonal antibodies can serve multiple functions; direct inhibition of c-erbB-2
      activity, recruitment of host effector mechanisms and direct or indirect delivery
      of toxic payloads. Clinical trials in patients with late stage disease have shown
      that many of these approaches are safe, feasible and relatively non-toxic, and,
      in some cases, objective responses have been seen. As with all immunotherapy, the
      greatest benefit is likely to be obtained in patients with minimal residual
      disease in an adjuvant setting; such studies are awaited with interest.

PMID- 15991937
TI  - Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the
      treatment of heart failure.
AB  - Losartan (COZAAR) is the prototype of a new class of potent and selective
      angiotensin II (AII) type 1 (AT(1)) receptor antagonists with the largest
      published preclinical and clinical data base. Since all of the AII antagonists
      are selective for the AT(1) receptor, these drugs should exhibit similar
      cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic
      profiles of these agents and their degree of affinity for the AT(1) receptor
      differ, it is likely that differences in clinical profiles between these drugs
      exist and will require investigation. Losartan (parent compound), has moderate
      affinity for the AT(1) receptor (competitive inhibition). Losartan is well
      absorbed orally as an active drug and is rapidly converted via oxidation in the
      human liver to a more potent metabolite (designated E3174) with an affinity 20-
      to 30-times greater for the AT(1) receptor (non-competitive inhibition). E3174
      has a half-life of 6 - 9 h; elimination is via renal and hepatic routes.
      Antihypertensive and, in heart failure patients, haemodynamic activity is
      observed over a 24 h period with once daily dosing. Over 6 million patients have
      been treated for hypertension with continued excellent tolerability. Clinical
      experience in heart failure is growing, and recent data suggest an improved
      survival with losartan versus captopril, a drug from the angiotensin-converting
      enzyme inhibitor class with proven benefit in this population. The current
      comprehensive losartan clinical end-point programme (4 large scale
      morbidity/mortality trials) should provide evidence regarding the efficacy of
      direct blockade of the AT(1) receptor with losartan compared to standard therapy:
      1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post
      Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension
      Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.

PMID- 15991938
TI  - Pharmacology of valsartan, an angiotensin II receptor antagonist.
AB  - Valsartan is the second orally-active, non-peptide angiotensin II receptor
      blocker to reach the market in Europe and the USA for the treatment of
      hypertension. Preclinical studies have demonstrated that this blocker is specific
      for the AT(1) receptor and has no affinity for the angiotensin II AT(2) receptor.
      Experimentally, valsartan dose-dependently inhibits the vasoconstriction induced
      by angiotensin II and lowers blood pressure in renin-dependent models of
      hypertension. Pharmacologically, oral valsartan is characterised by a low
      bioavailability but a rapid absorption and distribution with a half-life in
      keeping with once-daily administration. Thus, after oral administration, the
      maximal plasma concentration is reached 2 h after dosing and the elimination half
      life is about 6 h. Clinically, several dose-finding and comparative studies have
      demonstrated that valsartan is an effective and well-tolerated antihypertensive
      drug in patients with mild to moderate hypertension. Valsartan has also been
      shown to be effective in severe hypertension. Valsartan is at least as effective
      as ACE inhibitors, diuretics, beta-blockers and calcium antagonists. However,
      none of the side-effects observed with these latter agents, including cough and
      lower limb oedema, has been observed with the administration of valsartan. Three
      large clinical trials are now underway to demonstrate whether valsartan can
      reduce morbidity and mortality: one in hypertensives with a high cardiovascular
      risk profile (VALUE), one in patients with heart failure previously treated with
      an angiotensin-converting enzyme inhibitor (VAL-HeFT) and one in post-myocardial
      infarct patients (VALIANT). These studies will further define the place of
      valsartan beyond the treatment of hypertension.

PMID- 15991939
TI  - Myeloid growth factors in oncology.
AB  - Within the last decade haemopoietic growth factors have become established in the
      pharmacopoeia of oncology. In the form of granulocyte colony-stimulating factor
      (G-CSF), and to a lesser extent granulocyte-macrophage colony-stimulating factor
      (GM-CSF), these proteins are routinely used to accelerate restoration of
      neutrophil count after chemotherapy or bone marrow transplant. Their main advance
      has been the development of mobilisation protocols. Peripheral blood progenitor
      cells are induced to egress from the bone marrow and re-transfusion after
      myelosuppressive chemotherapy allows for a simple and more rapid form of
      autologous transplantation than bone marrow transplantation. This review will
      give a brief overview of the biology of haemopoiesis in relation to growth
      factors and the potential lines of further research. Although the established
      clinical uses of G-CSF will be discussed the main focus will be on the
      developmental applications, such as ex vivo haemopoiesis, dose intensification
      schedules and the application of growth factors in the therapy of haematological
      malignancies. The relevance of novel or more recently introduced recombinant
      haemopoietic growth factors will also be discussed in relation to these
      indications.

PMID- 15991940
TI  - The therapeutic potential of testosterone patches.
AB  - In the last decade, transdermal delivery of testosterone (T) has been shown to be
      a safe and effective means of treating male hypogonadism. Transdermal T patches
      can provide for physiologic androgen replacement in over 90% of men with
      hypogonadism. In addition, T patches have been shown to be equivalent to im. T
      esters in restoring normal male libido,sexual function and bone mineral density
      without harmful side-effects.Furthermore, in sharp contrast to periodic im.
      injections of T, transdermal T patches, when used daily, restore the normal
      circadian rhythm of T levels. The physiological and clinical importance of these
      circadian patterns,however, is presently unknown. The first transdermal patch to
      be marketed is applied to shaved scrotal skin. Newer patches can be applied to
      non-scrotal skin; however, these patches are associated with a significant rate
      of skin reactions that may require discontinuation. The main drawback to
      transdermal T delivery is cost, ten to twenty times the monthly cost of im. T,
      the method currently used to treat most hypogonadal men.Nevertheless, transdermal
      T patches constitute a major advance in the therapy of male hypogonadism as they
      allow for safe, non-invasive administration of T.

PMID- 15991941
TI  - Mechanisms of action of DNA vaccines.
AB  - The field of DNA vaccines can trace its inception to two papers which
      demonstrated that administration of plasmid DNA vectors expressing proteins
      resulted in expression in situ. Thereafter, the possible application of this
      technique to vaccine development was demonstrated through the induction of
      antibody responses in mice against a foreign protein, cellular immune responses
      against a viral antigen and protective efficacy in an infectious disease
      challenge model. Subsequently, the general utility of DNA vaccines in animal
      models of infectious and non-infectious disease has been established (for review,
      see [5]). Initially, most efforts were directed toward demonstration of
      effectiveness in particular disease models. Recently, however, more attention has
      been paid to gaining a better understanding of some of the underlying mechanisms
      of DNA vaccines. This review will focus on this new information and discuss it in
      the context of how it could benefit the development of more effective DNA
      vaccines.

PMID- 15991942
TI  - Post-statin approaches to hyperlipidaemia.
AB  - The advent of statins has virtually resolved the treatment of a majority of
      essential hypercholesterolaemic patients. Nevertheless, other abnormalities in
      lipoprotein metabolism, including such lipoprotein disturbances as
      hypertriglyceridaemia, mixed hyperlipidaemia, accumulation of small dense low
      density lipoprotein (LDL), high levels of lipoprotein (a) (Lp[a]) and hypo-HDL
      cholesterolaemia, although also highly atherogenic, are not as efficiently
      treated as essential hypercholesterolaemia. Pharmaceutical companies are
      improving new molecules directed against old targets (PPARalpha: fibrates) or
      creating original molecules directed against new targets (acyl CoA:cholesterol
      acyltransferase (ACAT), microsomal triglyceride transfer protein (MTP), retinoid
      X receptor (RXR)). Of the multitude of ACAT inhibitors, only a few have reached
      preliminary clinical studies: e.g., F-1394, Sch48461 and CI-1011. They reduce LDL
      cholesterol and atherosclerosis development in animals, partly by directly
      inhibiting cholesteryl ester formation in the artery wall. BW-USC-148 is a fibric
      acid derivative with ACAT-inhibiting activity. The hypocholesterolaemic activity
      for this novel ureido fibrate analogue was found to be over 100-fold greater than
      that of any 'second generation' fibrate in cholesterol-fed rats, mainly through
      its fibrate activity (PPARalpha activation) but not its ACAT activity. Targretin
      (LGD1069), a member of the rexinoid family (RXR activator), was shown to decrease
      triglyceridaemia and to increase HDL levels in hypertriglyceridaemic rats.
      Microsomal triglyceride transfer protein inhibitors are potent inhibitors of the
      synthesis of all the atherogenic apolipoprotein B-containing particles and are
      under development, but in vivo data are not yet available in literature. Vitamin
      E, an old molecule, should be used in the near future as a potent anti
      atherosclerotic treatment due to its anti-oxidant power. Results of preliminary
      gene therapy studies of homozygous familial hypercholesterolaemic patients and of
      hypo-HDL-cholesterolaemia in animals are promising but do not show hope for
      significant clinical use in the near future. The improvement in the understanding
      of the molecular mechanisms of dyslipoproteinaemia and atherosclerosis
      development, taken together with new strategies in drug design and drug
      synthesis, has led to the discovery of potent normolipidaemic drugs.

PMID- 15991943
TI  - FGF-1: a human growth factor in the induction of neoangiogenesis.
AB  - Currently available approaches for treating human coronary heart disease aim to
      relieve symptoms and the risk of myocardial infarction either by reducing
      myocardial oxygen demand, preventing further disease progression, restoring
      coronary blood flow pharmacologically or mechanically, or bypassing the stenotic
      lesions and obstructed coronary artery segments. Gene therapy, especially using
      angiogenic growth factors, has emerged recently as a potential new treatment for
      cardiovascular disease. Following extensive experimental research on angiogenic
      growth factors, the first clinical studies on patients with coronary heart
      disease and peripheral vascular lesions have been performed. The polypeptides
      fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF)
      appear to be particularly effective in initiating neovascularisation (neo
      angiogenesis) in hypoxic or ischaemic tissues. The first clinical study on
      patients with coronary heart disease treated by local intramyocardial injection
      of FGF-1 showed a 3-fold increase of capillary density mediated by the growth
      factor. Angiogenic therapy of the human myocardium introduces a new modality of
      treatment for coronary heart disease in terms of regulation of blood vessel
      growth. Beyond drug therapy, angioplasty and bypass surgery, this new approach
      may evolve into a fourth principle of treatment of atherosclerotic cardiovascular
      disease.

PMID- 15991944
TI  - Recent advances in transgenic model development for Alzheimer's disease.
AB  - The lack of a small animal model that represents major features of Alzheimer's
      disease has long been considered a major handicap for research and drug
      development. Transgenic technology has been used to introduce potential
      pathological start points as well as established genetic causes of the disease to
      trigger pathogenesis in a small animal model. This review describes various
      approaches, discusses the available transgenic mouse models and compares their
      similarities and differences, and their applicability for the testing of drugs
      aiming at a causal treatment of the disease.

PMID- 15991945
TI  - Levalbuterol hydrochloride.
AB  - Racemic salbutamol (racemic albuterol) ameliorates symptoms of asthma by
      activating beta-adrenoceptors on nerve, smooth muscle and inflammatory cells
      within the airways. Racemic salbutamol comprises equal proportions of 2 isomers:
      (S)-salbutamol and (R)-salbutamol, with the latter being exclusively responsible
      for activation of beta-adrenoceptors. Accordingly, within racemic salbutamol it
      is (R)-salbutamol that efficiently relieves obstruction of asthmatic airways and
      affords highly effective protection from bronchoconstrictor stimuli, including
      allergens. During regular use of racemic salbutamol, there is a progressive
      decline of protective efficacy and a corresponding intensification of airway
      responsiveness. This decline is largely absent during regular use of (R)
      salbutamol. Consequently, bronchodilator responses to sub-maximal doses of (R)
      salbutamol exceed responses to the equivalent dose of (R)-salbutamol given as the
      racemate. For example, in asthmatics with baseline FEVs <or= 60%, 1.25 mg of
      nebulised (R)-salbutamol achieved a maximal 52% change in FEV while 2.5 mg of
      racemic salbutamol only achieved a 38% change in FEV. Since extrapulmonary
      effects (e.g., tremor, heart rate) of beta agonists are related to dose and limit
      the use of beta agonist therapy, (R)-salbutamol at 0.63 mg provides uncompromised
      efficacy with marked reduction of side-effects. In addition to quantitative
      differences, the constituent isomers of salbutamol also exhibit qualitative
      differences. Thus, (R)-salbutamol inhibits activation of human eosinophils in
      vitro whereas, under the same conditions and concentrations, (S)-salbutamol
      augments activation of these cells. This property of (S)-salbutamol may explain
      why eosinophilia in induced sputum from subjects with allergic asthma is
      increased by regular use of racemic salbutamol. Similarly, the capacity of (R)
      salbutamol to suppress hyperresponsiveness of the airways can be contrasted with
      the capacity of (S)-salbutamol to intensify hyperresponsiveness. This action of
      (S)-salbutamol would explain why regular use of racemic salbutamol intensifies
      the bronchoconstrictor response to antigen in subjects with allergic asthma.
      Taken together, these findings imply that replacement of racemic salbutamol by
      (R)-salbutamol will diminish, or even eliminate, the anomalous actions that have
      curtailed the efficacy of racemic salbutamol. Pharmacokinetically, (R)-salbutamol
      exhibits near absolute conformational stability (i.e., no conversion to (S)
      salbutamol). If in vitro anti-inflammatory actions of (R)-salbutamol are also
      manifest in asthmatic airways, (R)-salbutamol could provide a novel approach to
      asthma therapy which combines bronchodilation and bronchoprotection with anti
      inflammatory efficacy.

PMID- 15991946
TI  - Thalidomide revisited: pharmacology and clinical applications.
AB  - Thalidomide is attracting new interest. Since the discovery of its remarkable
      efficacy in erythema nodosum leprosum, the drug has been used successfully in a
      variety of dermatologic and other diseases whose apparent common thread is immune
      dysregulation. Meanwhile, immunomodulatory and anti-inflammatory activities of
      thalidomide, particularly its inhibition of tumour necrosis factor alpha (TNF
      alpha), have been identified and elucidated. The drug has also been found to
      inhibit angiogenesis. Recent clinical trials have shown thalidomide effective in
      graft-versus-host disease, Behcet's syndrome and aphthous ulcers and wasting
      associated with HIV infection. Provocative findings in other diseases, including
      primary HIV infection, HIV-associated diarrhoea, inflammatory bowel disease,
      cancer and sepsis, have suggested additional clinical applications. Use of
      thalidomide in women capable of childbearing is controversial. However,
      guidelines have emerged for prevention of teratogenicity and peripheral
      neuropathy, the drug's other major adverse effect. With appropriate safeguards,
      thalidomide may hold benefit for patients with a broad variety of disorders in
      which existing treatments are inadequate. Its current use may represent only a
      small part of its therapeutic potential.

PMID- 15991947
TI  - 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC),
      September 24-27, 1998, San Diego, CA, USA.
AB  - This year's ICAAC meeting was dominated by exciting late-stage development
      antibiotics that represent breakthroughs in covering pathogens of unmet medical
      need, including drug-resistant pathogens. There are several exciting antibiotics
      in late-stage development, among them, linezolid, gatifloxacin, moxifloxacin, SB
      265805, HMR 3647, SCH27899 and the resurrected daptomycin. The development of new
      technology for screening and the cross-application into genomics have led to
      numerous breakthroughs in techniques and strategies for the identification of
      novel prokaryotic targets.

PMID- 15991948
TI  - The microbial postgenomic era: promises, problems and prospects.
AB  - The inevitable emergence and spread of resistance to new antibiotics entering the
      market necessitates a new approach in drug discovery. Novel classes of
      antimicrobial compounds are required that are not enfeebled by widespread
      resistance mechanisms. The favoured approach is to gain a better understanding of
      the essential pathways and cellular functions and then to select new unexploited
      targets. This strategy has coincided with the deposition of fully assembled
      genomic sequences of several bacteria in the public databases. Various
      technologies have been reported that, when optimised, will enable the analysis of
      global cellular processes at the molecular level thus greatly contributing to our
      understanding of cellular physiology. In this article, some of the major advances
      in technology, which are expected in the future to be essential for the optimal
      use of the information contained within the genomic sequences, will be outlined.

PMID- 15991949
TI  - Development of antivirals against influenza.
AB  - Morbidity and mortality due to influenza virus infections remain a major problem
      throughout the world. Yearly, medical costs and loss of productivity resulting
      from influenza infection are estimated to be in the range of 12 dollars bn in the
      USA. The predicted increases in the elderly and immune-deficient populations will
      make influenza an even greater threat in the future. Despite the availability of
      vaccines, they have been least effective in these high-risk populations. Coupled
      with the requirement for routine revaccination, the need for effective antiviral
      agents is illustrated. The currently approved drugs, amantadine, rimantadine and
      ribavirin (in some countries), have limitations. They are only inhibitory against
      influenza A viruses, are prone to adverse reactions and quickly give rise to
      resistant virus. This review examines current drug therapies, antivirals in
      development and possible future opportunities for anti-influenza drugs.

PMID- 15991950
TI  - The therapeutic potential of cationic peptides.
AB  - Novel classes of antibiotics that are useful against resistant bacteria are a
      major need in human medicine. Cationic antimicrobial peptides are utilised as
      nature's antibiotics, being produced constitutively or in response to infection
      in virtually every type of organism from plants and insects to man. Thus, these
      peptides are now being considered as potential antibiotics for infections. They
      have the following assets: structural diversity, rapid bactericidal action, a
      broad spectrum of activity that includes most of the clinically important
      resistant pathogens, and several ancillary activities which can include
      antifungal, antiviral, anti-endotoxin activities, and promotion of wound healing.
      Cationic peptides and proteins are now proceeding through clinical trials as
      topical antibiotics and anti-endotoxins.

PMID- 15991951
TI  - Importance of antifungal drug-resistance: clinical significance and need for
      novel therapy.
AB  - The incidence of fungal infections has increased dramatically over the past few
      decades due to the increase in the members of the population susceptible to such
      infections. This population includes individuals undergoing chemotherapy for
      cancer, those enduring long-term treatment with antibacterial agents, those
      receiving immunosuppressive drugs following transplantations, or those
      immunosuppressed due to diseases, such as AIDS, or malignancies. Newer antifungal
      agents, namely the triazoles, have aided in both the treatment of fungal
      infections and in the prevention of disease in susceptible individuals. However,
      resistance to the azoles, as well as to the polyenes, has resulted in clinical
      failures. Only a few potential antifungal targets have been exploited to date and
      there is a critical need for the discovery and development of novel antifungal
      agents that will result in improved therapy in this ever-expanding patient
      population. An increased intensity in the study of fungal pathogens at the
      molecular level holds the key to such advances.

PMID- 15991952
TI  - Efflux pumps in bacteria: overview, clinical relevance, and potential
      pharmaceutical target.
AB  - Trends in microbial resistance suggest a dramatic increase in the frequency of
      reports of multi-drug efflux pumps in bacteria and fungi. Although it is
      difficult to determine whether this increase is due to the increased attention
      given to this resistance mechanism, or an increase in frequency, efflux pumps are
      becoming an important consideration in resistance emergence. These efflux pumps
      comprise at least four different classes in Gram-positive and Gram-negative
      bacteria, as well as in Streptomyces and fungi. As more efflux pumps are
      characterised and studied, both biochemically and structurally, the opportunity
      for intervention may arise.

PMID- 15991953
TI  - DNA vaccines for the prophylaxis and modulation of HSV infections.
AB  - There is currently no acceptable vaccine available for the control of herpes
      simplex virus (HSV) infection. This review discusses the reasons for the past
      failures and evaluates the prospect that a fresh approach, such as that provided
      by plasmid DNA encoding viral proteins, could provide a solution. The issues
      addressed include immune responses generated by plasmids encoding glycoproteins
      of HSV, the mechanism of HSV, the nature of the response in neonates, mucosal
      barrier immunity, attempts at improving immunogenicity of DNA vaccines and the
      immunomodulation potential with DNA encoding cytokines. The review concludes that
      DNA vaccines against HSV may merit evaluation in man, but DNA vaccine research
      may be more useful for uncovering mechanisms by which the immune system functions
      against HSV infection.

PMID- 15991954
TI  - The therapeutic potential of agents acting via purine receptors.
AB  - A host of physiological processes associated with the cardiovascular (CV) system,
      central nervous system (CNS), and a variety of other organ systems and tissues
      are regulated by agents, primarily adenosine (ado) and adenosine triphosphate
      (ATP), that act via cell-surface purine receptors. These receptors have therefore
      been the focus of a variety of programmes directed at the discovery and
      development of new therapeutic agents, most notably for the treatment of
      disorders of the CV system. Currently, only a handful of agents, including ado,
      theophylline, dipyridamole, and ticlopidine, are approved for clinical use. A
      variety of new agents intended for use in CV disease, disorders of the CNS, such
      as Parkinson's disease, treatment of pain, inflammatory disorders, and diverse
      other pathophysiological conditions are in clinical development. Historically,
      ado receptors have been the primary target. Recent research efforts have begun to
      examine alternative strategies including agents that modulate endogenous levels
      of extracellular ado and agents that act via P(2) receptors.

PMID- 15991955
TI  - Meningococcal vaccine development: a novel approach.
AB  - Neisseria meningitidis is a major world-wide cause of meningitis. Effective
      capsular polysaccharide (CPS) vaccines that elicit CPS-specific bactericidal (BC)
      antibodies were previously developed and licensed to protect against
      meningococcal disease. However, due to their T-cell independent character, CPS
      vaccines are useless in infants and do not provide immunological memory or long
      lasting protection in adults. CPS-protein conjugate vaccines are being developed
      to improve and broaden vaccine efficacy by creating T-cell dependent antigens.
      However, group B meningococci (GBM) are responsible for nearly half of
      meningococcal disease and possess a CPS, composed of polysialic acid, that is
      poorly immunogenic. N-propionyl (NPr) modification of the GBM polysaccharide
      (GBMP) has enhanced its immunogenicity, but BC antibodies are not induced at high
      levels, even when conjugated to conventional protein carriers, unless adjuvants
      stronger than aluminium hydroxide are used. We have chosen to couple the NPr-GBMP
      by reductive amination to a recombinant GBM class 3 porin (rPorB), which we have
      shown to modulate the immune response in animals towards the production of CPS
      specific BC antibodies. We have also combined this conjugate with similar CPS
      rPorB conjugates for groups A and C meningococci to form a trivalent A/B/C
      conjugate vaccine. This trivalent meningococcal vaccine has been shown to be safe
      and highly immunogenic in mice and non human primates, generating CPS-specific BC
      antibodies for each of the 3 major serogroups, which should provide world-wide
      protection against meningococcal disease.

PMID- 15991956
TI  - Chemotherapy of mycobacterial infections: molecular action of established drugs
      and investigational agents.
AB  - Infections caused by mycobacteria constitute important global health problems.
      During the last 50 years a number of drugs have achieved an established role in
      the therapy of these infections. These drugs, which are often used in
      combination, comprise both broad-spectrum agents that display antibacterial
      activity against mycobacteria and other organisms and narrow-spectrum agents
      whose activity is primarily restricted to mycobacteria, or even to individual
      mycobacterial species. In addition to the established agents, a number of
      investigational agents with antimycobacterial activity are at various stages in
      the research and development process. Several of the newer agents have arisen
      from the need to develop new drugs to combat the problems of emerging resistance
      to established agents. The mechanisms of action of the established drugs and
      investigational agents are reviewed in this update.

PMID- 15991957
TI  - Developments in antipsychotic drugs - an update.
AB  - Antipsychotic drug research has recently made much progress. Over the past two
      years several new drugs have been introduced for the treatment of schizophrenia
      and more compounds are shortly to be released. Pharmacological studies, improved
      behavioural models and modern imaging techniques have all contributed to a better
      understanding of the mechanisms of antipsychotic drug action. Some of the
      developments that have been made over the past year are reviewed here.

PMID- 15991958
TI  - Clinical trials of chemotherapy for falciparum malaria.
AB  - Plasmodium falciparum remains one of the World's most prevalent and devastating
      pathogens. Mainly for economic reasons, the parasite's ability to develop
      resistance to drugs has not been matched by the rate at which new compounds are
      developed. Even so, there are new drugs (or new combinations of old drugs)
      currently under investigation, or in the process of development (at the moment):
      Pyronaridine, a well-tolerated, synthetic drug that may have utility for multi
      resistant falciparum malaria in many parts of the world; however,problems remain
      over the formulation of this drug (which is a major determinant of its
      bioavailability) and its eventual cost. Chlorproguanil-dapsone (lap dap) is being
      studied as a possible low-cost'successor' to pyrimethamine-sulfadoxine; the
      utility of chlorproguanil-dapsone as 'salvage' therapy for clinical cases of
      pyrimethamine-sulfadoxine failure has yet to be tested in clinical trials.
      Atovaquone-proguanil (malarone) has utility against multi-resistant parasites;
      however, it is likely to be expensive (but is currently being provided free-of
      charge in certain areas of Africa). Artemether-benflumetol (coartemether)
      combines the advantages of artemether (a rapid reduction in parasite load) with a
      second drug that reduces the risk of recrudescence; the cost of this combination
      is unclear. Rectal artesunate is being studied as an intervention to reduce the
      proportion of children with falciparum malaria who deteriorate to severe disease;
      the formulation is appropriate for use in rural health centres.

PMID- 15991959
TI  - Docetaxel (Taxotere) - an update.
AB  - The development of docetaxel, a member of the taxoid family, has been recent and
      rapid. Phase I studies recommend that a dose of 100 mg/m(2) be administered every
      three weeks in a 1-h infusion. These studies have also demonstrated that the
      major dose-limiting toxicity is neutropenia. Major clinical research projects are
      now being carried out for breast cancer, non-small-cell lung cancer (NSCLC),
      squamous cell carcinoma of the head and neck (SCCHN) and gastric cancer. In
      advanced and metastatic NSCLC, Phase II studies have shown a response rate of 30 
      40%, and responses have been obtained in cis-platinum failures. In advanced and
      metastatic breast cancer, first-line treatment has yielded a response rate of 54 
      68%, and the rate for second-line response is only slightly lower, indicating an
      absence of cross-resistance. Phase II combination studies with docetaxel are in
      progress, and preliminary results are promising. The first Phase III study
      demonstrated preliminary response rates significantly higher than seen with
      doxorubicin, although survival data have not yet been published. Fewer results
      are available from SCCHN studies, but response rates have been encouraging
      (around 40%). Although further long-term data are needed to determine the precise
      role of docetaxel in combination with other drugs, it is apparent that this
      promising drug shows one of the best response rates for monotherapy in NSCLC and
      breast cancer.

PMID- 15991960
TI  - IBC's 5th Annual Conference on Blood Substitutes.
AB  - IBC's 5(th) Annual Conference on Blood Substitutes was held on November 20-21,
      1997. Approximately 100 medical researchers, academic scientists, blood
      substitute company speakers and representatives from major pharmaceutical
      companies with an interest or partner in the field attended. The papers presented
      focused on the progress in clinical trials for those compounds in human study, on
      preclinical models for predicting efficacy in humans, and on novel approaches and
      agents for the delivery of oxygen. Both perfluorocarbons (PFC) and haemoglobin
      based oxygen carriers were described. Several lectures addressed the history of
      the field and future directions for laboratory and clinical investigation. The
      following is a summary of some of the presentations. This summary is divided into
      3 sections. The first section provides a historical overview and discusses the
      changes in the perceived need for a blood substitute. Section 2 comprises an
      update of company activities. The final section focuses on likely future
      directions for laboratory and human clinical study.

PMID- 15991961
TI  - Future therapies for the prevention and treatment of venous and arterial
      thrombosis.
AB  - The incidence of thrombosis as a complication of invasive surgery, in cancer
      patients, as a cause or complication of stroke, acute myocardial infarction
      (AMI), thrombolysis, unstable angina (UA) or angioplasty is substantial. To
      better serve this patient population in the prevention and prophylaxis of
      thrombosis, new types of anticoagulant drugs are under development by the
      pharmaceutical industry. The goal of these efforts are orally-active
      anticoagulants with specificity and pharmacokinetic properties that could
      translate into better control of anticoagulation and thrombosis and less bleading
      liability compared to the currently used anticoagulants: heparin, the low
      molecular weight heparins and warfarin. Various approaches for which there is a
      great deal of activity include: tissue factor/Factor VIIa inhibitors, Factor Xa
      inhibitors, thrombin inhibitors, glycoprotein IIb/IIIa antagonists. There is also
      interest in Factor IXa inhibitors, thrombin receptor antagonists and inhibitors
      of plasminogen activator inhibitor-1.

PMID- 15991962
TI  - Persistent infection and vascular disease: a systematic review.
AB  - More than 150 epidemiological or clinical studies have reported on associations
      between vascular disease and the presence of certain persistent bacterial and
      viral agents, or of clinical conditions (e.g., periodontal disease) that are
      associated with persistent infection. This article provides a review of such
      studies, particularly in relation to Helicobacter pylori, Chlamydia pneumoniae,
      dental disease and cytomegalovirus (CMV), as well as references to possible
      mechanisms. The association between coronary heart disease and H. pylori or
      between heart disease and dental disease may be accounted for by residual
      confounding. Although markers of C. pneumoniae infection are around twenty times
      more common in atherosclerotic plaques than in disease-free blood vessels, the
      sequence of infection and disease is uncertain. For CMV, a limited number of
      patients with classic atherosclerotic coronary heart disease have been
      investigated in seroepidemiological studies. For all such agents, better and
      larger seroepidemiological and pathology-based studies are needed to resolve
      these uncertainties, as well as - at some stage - large-scale, randomised
      intervention studies.

PMID- 15991963
TI  - New prospects for lipid-lowering drugs.
AB  - The advent of 3-hydroxy-methylglutaryl Co-enzyme A (HMG-CoA) reductase inhibitors
      has dramatically improved the treatment of dyslipidaemia and the prevention of
      atherosclerosis over the past 10 years. Similar but less marked benefit had
      previously been demonstrated for fibrates and bile acid sequestrants, which were
      first introduced over 30 years ago and are still in use. The discovery that
      fibrates are ligands for peroxisome proliferator activated receptors (PPARs) may
      lead to innovations in the future. However, most of the compounds now undergoing
      clinical trials are either HMG-CoA reductase inhibitors or bile acid
      sequestrants, which is indicative of the current emphasis on lowering low density
      lipoprotein (LDL) cholesterol. Drugs in an earlier stage of development include
      inhibitors of squalene synthase, which have yet to fulfil their initial promise,
      and of acylcholesterolacyltransferase (ACAT) and microsomal triglyceride transfer
      protein (MTP). Most of the earlier ACAT inhibitors were poorly absorbed, but
      compounds with better bioavailability hold considerable promise by virtue of
      their ability to inhibit ACAT in liver and arterial wall macrophages. MTP
      inhibitors have the potential to drastically reduce apolipoprotein B (apoB)
      secretion, but safety issues could negate this advantage. Thus, despite the
      impact of statins, the development of new lipid-modulating drugs continues to be
      a dynamic field of research.

PMID- 15991964
TI  - Development and therapeutic indications of orally-active non-peptide vasopressin
      receptor antagonists.
AB  - Vasopressin (AVP) and oxytocin (OT) are cyclic nonapeptides whose actions are
      mediated by the stimulation of specific G-protein-coupled receptors (GPCRs)
      currently classified into V(1)-vascular (V(1)R), V(2)-renal (V(2)R) and V(3)
      pituitary (V(3)R) AVP receptors and OT receptors (OTR). The signal transduction
      pathways coupled to the different subtypes of AVP/OT receptors are reviewed. The
      recent cloning of the different members of the AVP/OT family of receptors now
      allows the extensive characterisation of the molecular determinants involved in
      agonist and antagonist binding, as well as signal transduction coupling.
      Potential therapeutic uses of AVP receptor antagonists include: the blockade of
      V(1)-vascular AVP receptors in arterial hypertension, congestive heart failure
      (CHF) and peripheral vascular diseases; the blockade of V(2)-renal AVP receptors
      in the syndrome of inappropriate vasopressin secretion, CHF, liver cirrhosis,
      nephrotic syndrome and any state of excessive retention of free water and
      subsequent hyponatraemia; the blockade of V(3)-pituitary AVP receptors in
      adrenocorticotropin (ACTH)-secreting tumours. The pharmacological and clinical
      profile of orally-active non-peptide AVP receptor antagonists is reviewed.

PMID- 15991965
TI  - Comparative pharmacology of the angiotensin II receptor antagonists.
AB  - The non-peptide angiotensin II (AII) receptor antagonists are a new class of
      compounds that are continuing to be developed as therapeutic agents for the
      treatment of hypertension, heart failure (HF) and chronic renal disease (CRD).
      Several of these compounds are currently available for therapeutic use in the USA
      and the European community with several more in clinical trials and in
      development. Compounds in this new class are as effective as angiotensin
      converting enzyme (ACE) inhibitors in treating hypertensive patients and appeared
      to have a similar therapeutic profile to ACE inhibitors in patients with HF and
      CRD. One clinical advantage of the AII receptor antagonists over ACE inhibitors
      is an improved side-effect profile with the absence of the persistent dry cough
      associated with ACE inhibitor therapy. To date, it is clear that the AII receptor
      antagonists are effective antihypertensive agents. Clinical trials are currently
      in progress to determine the therapeutic efficacy of these drugs in the treatment
      of HF and progressive renal disease.

PMID- 15991966
TI  - Anti-aldosterone therapy in the treatment of heart failure: new thoughts on an
      old hormone.
AB  - Activation of the renin-angiotensin-aldosterone system (RAAS) is a prominent
      feature of left ventricular dysfunction and plays an important role in the
      progression of chronic heart failure. Clinical and animal studies investigating
      agents that interrupt this hormonal system have focused primarily on the proximal
      constituents of the RAAS, namely angiotensin converting enzyme inhibitors and
      angiotensin II receptor antagonists, and have largely neglected the possible
      pathological consequences of another hormone in the system, aldosterone. Clinical
      evidence indicates that aldosterone plays an important role in chronic heart
      failure, even when other RAAS inhibiting agents are employed. Moreover, animal
      studies have indicated that aldosterone, in addition to important renal effects,
      has direct cardiac and vascular effects. These data suggest that an anti
      aldosterone therapeutic may provide important protection in chronic heart
      failure. Currently, only one therapeutic is available, spironolactone
      (Aldactone), and recent clinical studies support the contention that the addition
      of spironolactone to standard heart failure therapy provides additional benefit.
      A highly selective aldosterone receptor antagonist, eplerenone, is currently in
      clinical development. Data from this new agent should provide important evidence
      supporting the benefit of anti-aldosterone therapy in chronic heart failure,
      which may encourage physicians to include an anti-aldosterone agent in the
      armamentarium of therapeutics currently used to combat chronic heart failure.

PMID- 15991967
TI  - Therapeutic advances of new fluoroquinolones.
AB  - Fluoroquinolone antimicrobials have been available for over 10 years. Recent
      modifications to nuclear side-chains have enhanced both the antimicrobial and
      pharmacokinetic profiles of this class. Rapidly increasing antimicrobial
      resistance among community and hospital bacterial pathogens has diminished
      therapeutic options. Infections caused by such pathogens, including drug
      resistant Streptococcus pneumoniae and multi-resistant Enterobacteriaceae are now
      treatable by few classes of antibacterials, one of these being the
      fluoroquinolones. Ciprofloxacin was one of the first effective agents available
      in both iv. and oral formulations for the treatment of Gram-negative infection,
      resistant to other antibiotics. More recent developments, such as sparfloxacin
      and grepafloxacin, are more effective in vitro against Gram-positive pathogens,
      although their safety profile may be less promising. Fluoroquinolones not yet in
      widespread clinical use, including trovafloxacin, clinafloxacin and moxifloxacin,
      hold considerable promise as community 'respiratory antimicrobials' and the
      results of clinical trials are awaited with anticipation. In this review, the
      three generations of fluoroquinolone development are examined and the relative
      antimicrobial, pharmacokinetic, clinical and safety profiles of available and
      developmental quinolones are compared.

PMID- 15991968
TI  - The therapeutic potential of islet cell transplant in the treatment of diabetes.
AB  - Diabetic patients requiring insulin treatment are at an increased risk of
      developing chronic complications affecting the eye, kidney and heart as well as
      other disabilities, such as neurological and vascular disease. The Diabetes
      Control and Complications Trial (DCCT) showed that the development of these
      complications can be profoundly reduced or even prevented by strict glycaemic
      control through intensive insulin therapy. The DCCT study, which was concluded in
      1993, administered intensive insulin treatment either by multiple (three or four
      per day) insulin injections or by an external insulin pump. However, it is both
      stressful and difficult to achieve effective glycaemic control by these methods.
      Furthermore, intensive insulin administration imposes a significant danger of
      hypoglycaemia to patients receiving this treatment. Biological replacement of the
      destroyed insulin-producing B-cells of pancreatic islets, with normal functioning
      islet transplants, remains the best option with which to achieve strict glycaemic
      control in diabetic patients requiring insulin treatment. The ultimate goal in
      transplantation is the unlimited availability of organs/tissues to be
      transplanted in a simple procedure that requires little or no immunosuppression.
      Other obstacles have also contributed to the delay in islet transplantation
      becoming a clinical reality. There are now good methods for isolating long-term
      functional islets, and it has been proposed that these islets can be
      immunoisolated by microencapsulation to prevent transplant rejection, an approach
      that could easily lead to the use of islet xenografts in human diabetic patients.
      Therefore, the development of microencapsulated islets promises to solve the two
      major obstacles to clinical islet transplantation, transplant rejection and
      shortage of human islets. This technique has enormous potential as a viable
      treatment for diabetic patients requiring insulin therapy to achieve glycaemic
      control.

PMID- 15991969
TI  - Basic fibroblast growth factor and the complexity of tumour angiogenesis.
AB  - Intrinsic biochemical properties of basic fibroblast growth factor (bFGF) do not
      adequately explain its potent pro-angiogenic activity. In vivo, bFGF can act in
      concert with other modulators of angiogenesis, such as vascular endothelial
      growth factor (VEGF). It is suggested that due to the complexity of angiogenic
      growth factor networks the process may be regulated in a non-linear fashion.

PMID- 15991970
TI  - Skin substitutes to enhance wound healing.
AB  - Biologically-based skin substitutes have developed as commercial products over
      the last 5 years. The first generation includes the collagen-based synthetic
      device, Integra, and Alloderm, which is based on devitalised and cross-linked
      human dermis. These are used as dermal replacements for third degree burns.
      Within the last year, the tissue-engineered product, Dermagraft-TC, has become
      available. While originally intended as a temporary covering for severe burns,
      Dermagraft-TC has proved to markedly improve the healing of deep second degree
      burns. The earliest living skin substitutes used autologous keratinocytes
      expanded in vitro. Two new products containing living cells, Dermagraft and
      Apligraf, are expected to be approved shortly for diabetic foot ulcers and venous
      stasis ulcers, respectively. Dermagraft is produced by growing human fibroblasts
      on a three-dimensional scaffold. The cells actively proliferate and lay down
      extracellular matrix to generate a papillary dermis-like device that shows a
      combination of angiogenic, growth factor and cell adhesion properties that
      enhance healing in diabetic foot ulcers. The production of Apligraf includes
      casting human fibroblasts in collagen, in order to generate a dermal equivalent
      on which is grown an epidermis. The structure is akin to a skin graft and is so
      applied. Despite Dermagraft and Apligraf being of allogeneic origin, rejection
      has not been an issue in clinical trials and possible contamination by pathogens
      has been eliminated as a concern through extensive testing. These developments
      represent a new concept and are expected to revolutionise wound care. They may
      also provide a platform for gene therapy applications.

PMID- 15991971
TI  - Ongoing clinical trials of anti-platelet agents in the management of acute
      ischaemic coronary syndromes.
AB  - Acute ischaemic coronary syndromes, the clinical sequelae of thrombosis over a
      fissured atherosclerotic plaque within the coronary circulation, are the leading
      cause of death and hospitalisation in Western countries. Platelets are
      fundamental for the initiation and continuation of thrombosis, and currently
      available anti-platelet agents such as aspirin significantly improve the clinical
      outcome of patients with these syndromes. Therapeutic success with available
      therapy is however not universal, and adverse clinical event rates remain high.
      Several new classes of agents with a variety of anti-platelet actions are
      currently under development. Those which inhibit the final common pathway of
      platelet aggregation, the glycoprotein (GP) IIb/IIIa receptor, appear to show the
      most promise. Much clinical trial evidence already exists supporting the use of
      GP IIb/IIIa receptor antagonists in the management of acute ischaemic coronary
      syndromes. Several clinical studies are underway to further refine this knowledge
      base, and to assess their efficacy in a variety of novel applications.

PMID- 15991972
TI  - Raltitrexed (Tomudex).
AB  - Raltitrexed (Tomudex) is a new specific, mixed non-competitive inhibitor of
      thymidylate synthase indicated for use in the therapy of advanced colorectal
      cancer. Phase I and II studies defined a maximum tolerated dose of 3.0 mg/m(2)
      administered as a 15-min i.v. infusion every 3 weeks: this dose proved active in
      a range of malignancies, but most significantly in advanced colorectal cancer.
      Phase III studies in patients with advanced colorectal cancer indicate similar
      efficacy with raltitrexed monotherapy and combination therapy with 5-fluorouracil
      + low or high dose leucovorin (5-FU + LV) (Mayo or Machover regimens,
      respectively). Major toxicity in the various studies of raltitrexed included
      gastrointestinal effects, haematological suppression, asthenia and reversible
      asymptomatic increases in hepatic transaminases. However, patients receiving 5-FU
      + LV experienced more severe leucopaenia and mucositis than patients receiving
      raltitrexed: this translated into fewer toxicity-related dosage reductions.
      Raltitrexed is therefore as effective as but better tolerated and accepted than 5
      FU + LV. Thus, raltitrexed offers the first alternative to 5-FU-based therapy in
      advanced colorectal cancer; furthermore, the mode of action of the drug offers
      the potential for synergy with agents that act via other molecular mechanisms.

PMID- 15991973
TI  - IBC's conference on antibody engineering; new technology, application and
      commercialisation.
AB  - This was the first antibody engineering conference held by IBC Conferences in the
      UK, and was the European equivalent of the annual US meeting held in San Diego.
      The conference provided a forum for an update on progress in all aspects of
      antibody engineering. Topics covered ranged from the design of libraries and new
      selection techniques to news of the first engineered antibodies to enter clinical
      trials. Library size and diversity were shown to have increased dramatically in
      the last few years, and new formats have been introduced. In parallel,
      improvements to existing applications and the development of novel selection
      technologies were shown to improve accessibility to new targets. Exciting
      developments included phenotypic selections, ribosome display, improvements to
      bispecific design and the design of active intracellular antibodies. The data
      generated for recombinant antibodies in the clinic are very promising, with some
      antibodies demonstrating improvements over conventional therapies and others
      targeting diseases where no treatment is currently available. Presented below is
      a summary of the highlights of the conference, with particular focus on natural
      antibody phage libraries, and lead candidates derived from these libraries
      currently in clinical trials.

PMID- 15991974
TI  - Antibody-based therapies as anti-infective agents.
AB  - Antibody-based therapies are effective against a wide variety of pathogens.
      Historically, antibody-based therapies were largely abandoned with the advent of
      antimicrobial chemotherapy, due to the toxicity associated with the
      administration of heterologous immune sera. As a class, antibody-based therapies
      have significant advantages and disadvantages relative to conventional
      antimicrobial chemotherapy. Advantages include versatility, specificity, and
      antimicrobial activities not available in antibiotic drugs, such as toxin and
      viral neutralisation, opsonisation, complement activation and the enhancement of
      host immune function. Disadvantages include expense, the necessity for early and
      accurate diagnosis prior to use, and the complex logistics necessary for
      therapeutic use. Advances in antibody technology have minimised some of the
      disadvantages associated with antibody therapy. In recent years, the therapy of
      infectious diseases has been complicated by the emergence of new pathogens, the
      spread of antibiotic-resistant strains and the relative inefficacy of
      antimicrobial chemotherapy in immunocompromised hosts. This has led to renewed
      interest in the utilisation of antibody-based therapies as anti-infectives. Many
      opportunities for developing antibody-based drugs now exist in areas where the
      available antimicrobial therapies are inadequate.

PMID- 15991975
TI  - Novel complement inhibitors.
AB  - The complement system provides natural immunity against microbes and is an
      effector arm of antibody-mediated humoral immunity. It promotes the inflammatory
      process by activating cells and facilitates microbial destruction through
      opsonisation and lysis. Given this tissue damaging potential, it is not
      surprising that nearly half of the proteins of the complement system are
      regulators. The complement system can mediate undesirable cellular damage in
      autoantibody-mediated conditions, for example myasthenia gravis, immune-complex
      excess syndromes, such as systemic lupus erythaematosus, ischaemia-reperfusion
      states, hyperacute rejection of transplants, organ failure conditions (e.g.,
      adult respiratory distress syndrome [ARDS]), Alzheimer's disease (AD) and related
      neurodegenerative disorders. A complement inhibitor has been lacking in the
      therapeutic arsenal. However, there are now several such agents being assessed in
      clinical trials and others under development. Current approaches include soluble
      versions of membrane regulatory proteins, humanised antibodies to components,
      small molecule inhibitors at various stages of the pathway and transgenic animals
      expressing human complement regulators for xenotransplantation. These and other
      strategies should lead to an effective means with which to inhibit complement
      activation in clinical medicine.

PMID- 15991976
TI  - Capsular polysaccharide-protein conjugate vaccines and intravenous
      immunoglobulins.
AB  - Capsular polysaccharides (CPs), present on the surface of most pathogenic
      bacteria, have been recognised as virulence factors. Antibodies specific to these
      polysaccharides can mediate the killing of these bacteria by phagocytes in the
      presence of complement. The conjugation of polysaccharides to carrier proteins
      enhances their immunogenicity and renders the immune response T-cell dependent.
      The currently licensed capsular polysaccharide vaccines and polysaccharide
      protein conjugate vaccines under development for the prevention of bacterial
      infections will be discussed in this review. Use of these vaccines for active
      vaccination and for the vaccination of healthy plasma donors to produce
      hyperimmune iv. immunoglobulins for the passive immunisation of appropriate
      patient populations is also discussed.

PMID- 15991977
TI  - Recent advances in immunological adjuvants: the development of particulate
      antigen delivery systems.
AB  - New generation vaccines, including those based on recombinant proteins, are safer
      than traditional vaccines, but are less immunogenic. Therefore, there is an
      urgent need for the development of new and improved vaccine adjuvants. A number
      of potent immunostimulatory molecules obtained from bacterial cells or plants
      have been extensively evaluated as adjuvants. However, a number of these
      molecules have displayed significant toxicity, both in preclinical animal models
      and in human clinical trials. An alternative approach to the development of novel
      adjuvants involves the preparation of particulate antigen delivery systems of
      similar dimensions to natural pathogens. In the absence of additional
      immunostimulatory molecules, emulsion droplets and microparticles have been shown
      to be potent adjuvants for the induction of both humoral and cell-mediated immune
      responses following systemic administration. Moreover, particulate delivery
      systems have been shown to display an acceptable toxicity profile in a number of
      clinical trials. Particulate antigen delivery systems also have the potential to
      function as potent adjuvants following administration by mucosal routes,
      including oral and intranasal. An alternative approach to the mucosal delivery of
      vaccines involves the use of genetically detoxified mutant toxins, e.g., LT-K63,
      as mucosal adjuvants. The use of novel adjuvants and antigen delivery systems is
      likely to extend the use of vaccines into the area of therapeutics, involving the
      eradication of infectious diseases and cancers, or the amelioration of autoimmune
      disorders.

PMID- 15991978
TI  - Interleukin-2 in the treatment of malignant melanoma.
AB  - Interleukin-2 (IL-2) is a lymphokine produced by T-cells that has a number of
      immunomodulatory effects. Treatment of metastatic melanoma with recombinant
      interleukin-2 (rIL-2)-based therapies represents one of the earliest attempts at
      systemic immunomodulation as a therapy for cancer. Initial studies showed
      objective response rates with rIL-2 therapy alone in the range of 15 - 20% with
      some durable responses. A multitude of studies have been undertaken with various
      rIL-2 regimens, with and without co-administration of lymphokine-activated cells
      or tumour-infiltrating lymphocytes. However, the optimum dose and treatment
      schedule for rIL-2-based therapy in metastatic melanoma, remains controversial.
      There are also no clear immunological parameters that can reliably predict
      antitumour response to rIL-2-based therapy. Ongoing research remains active in
      exploring the role of rIL-2 in the therapy of malignant melanoma (MM),
      particularly in conjunction with cytotoxic therapy.

PMID- 15991979
TI  - Immunoscreening protocols for the identification of clinically useful antibodies
      and antigens.
AB  - The antigen-antibody interaction is a powerful tool for the immuno-screening of
      several diseases, including cancer and genetic disorders. The high specificity of
      monoclonal antibodies (mAbs) enables them to target antigens and form complexes
      that can be detected with enzymes, radionuclides, fluorescent dyes or other
      markers. The antibody molecule, which has an antigen binding site, can be used as
      an intact molecule or as a fragment, for example, F(ab)(2), Fab, Fv or scFv.
      Similarly, the antigen can also be varied. In this review, immuno-screening
      techniques that can be used to detect clinically relevant antibody-antigen
      interactions will be discussed.

PMID- 15991980
TI  - Urokinase receptor antagonists: novel agents for the treatment of cancer.
AB  - The interaction between the urokinase receptor (uPAR) and its ligand urokinase
      (uPA) mediates phenomena such as tissue remodelling, chemotaxis, tumour invasion,
      dissemination, proliferation, and angiogenesis. The broad-spectrum of biological
      processes that the uPA/uPAR interaction plays a role in has led researchers to
      speculate that this interaction may be a useful molecular target for therapeutic
      intervention in several pathological conditions, particularly in the prevention
      and inhibition of the dissemination of cancer cells. In syngeneic and xenograft
      murine tumour models, in which metastasis is driven by the uPA/uPAR interaction,
      inhibition of primary tumour growth, metastasis and angiogenesis has been shown
      with several proteins acting as uPAR antagonists. Immunohistochemistry, in
      conjunction with prognostic studies, has implicated the uPA/uPAR interaction in
      the dissemination of tumours, such as malignant melanoma, colon cancer, non-small
      cell lung cancer (NSCLC) and stomach cancer, as well as breast and ovarian
      carcinomas. A potential inhibitor of the uPA/uPAR interaction should result in a
      significant increase in the disease-free interval and survival time following
      resection of the primary tumour in a clinical Minimal Residual Disease (MRD)
      setting. Low molecular weight uPAR antagonists should be orally active, and have
      few side-effects, excellent bioavailability, favourable pharmacokinetic
      properties and a long half-life. Furthermore, these compounds should be able to
      inhibit the dissemination of cancer cells without the need for targeted drug and
      vector delivery.

PMID- 15991981
TI  - The therapeutic potential of synthetic multivalent carbohydrates.
AB  - Recent progress has been made in constructing synthetic multivalent carbohydrate
      ligands targeted at known or probable multivalent carbohydrate ligand receptors.
      Multivalency can dramatically compensate for the weak affinities of individual
      carbohydrate ligand moieties. Multivalent branched ligand mimetics have been
      described bearing multiple mannoside, galactoside, lactoside and Sialyl Lewis X
      (SLe(x)) moieties. New methods for polymeric backbone construction have provided
      glyco-polymers of defined and controllable size. Promising examples of
      multivalent ligands giving significant increases in binding potency are being
      pursued. These types of agents have extensive therapeutic potential in treating
      infectious diseases or host abnormalities, and also offer exciting potential as
      drug-conjugate cell-targeting agents.

PMID- 15991982
TI  - The role of combinations of HIV protease inhibitors in the management of persons
      with HIV infection.
AB  - The current standard of care in antiretroviral therapy includes two nucleoside
      analogue reverse transcriptase inhibitors (NRTIs) plus a potent third agent,
      usually an HIV protease inhibitor (PI). However, around 20 - 30% of patients
      initiating therapy in clinical studies, and probably more in clinical practice,
      fail to achieve an optimal therapeutic response, a sustained undectectable viral
      load, using these regimens. Additionally, many triple therapy regimens currently
      require three times per day dosing, making treatment adherence difficult to
      sustain. Combinations of two PIs with or without NRTIs provide impressive
      reductions in viral load, with emerging data suggesting a higher proportion of
      patients on four drug regimens achieving below detection responses than those on
      three drug regimens. Additionally, pharmacokinetic interactions between PIs
      provide the potential for both dose reductions and twice daily dosing with PI
      combinations. However, limited resistance data are available from dual PI
      failures, and concerns regarding disturbances in fat metabolism, lipodystrophy
      and glucose intolerance remain obstacles to the widespread use of these regimens
      as initial therapy.

PMID- 15991983
TI  - Ongoing and planned clinical trials of anti-arrhythmic drugs: an update.
AB  - Anti-arrhythmic drug therapy is frequently used for the control of ventricular
      arrhythmias in the setting of heart disease. These agents have been used in many
      randomised clinical trials in an attempt to demonstrate improved survival.
      However, most studies have been disappointing, showing little or no improvement
      in survival, and, in some cases, deterioration. This report reviews ongoing
      clinical trials designed to evaluate survival in specific patient populations.

PMID- 15991984
TI  - Imiquimod 5% cream (Aldara).
AB  - Imiquimod is a novel synthetic molecule with potent immune-modifying activities.
      Formulated in a 5% vanishing cream as Aldara, this self-applied therapy has shown
      good efficacy and safety in the treatment of external genital and perianal warts
      caused by human papillomavirus (HPV) infection (Condyloma acuminata). The
      molecule does not demonstrate direct antiviral activity, but through induction of
      cytokines results in immune-based resolution of wart tissue and reduction of
      viral burden. Phase III trials of imiquimod have demonstrated that patients who
      experience complete clearance of either new or recalcitrant warts tend to remain
      clear, possibly related to Th1 immune recognition and memory. Self-application,
      good tolerability and a unique mechanism of action combine to make imiquimod a
      reasonable first-line therapy for genital warts. The effects of imiquimod on
      immune function suggest several potential uses. Preclinical studies of infection
      with herpes simplex virus (HSV), cutaneous leishmaniasis, Rift Valley Fever virus
      and vesiculostomatitis virus have shown reduced viral persistence, reduced
      recurrence (HSV) and diminished pathology (Leishmania donovani). In a murine
      tumour model using the FCB bladder cancer cell line, imiquimod behaves as a
      potent adjuvant leading to immune-based tumour cell eradication and immunity
      against subsequent FCB cell challenge. The ability of imiquimod to induce
      significant production of interferon alpha (IFN-alpha) by monocytes/macrophages
      suggests that diseases responsive to recombinant interferon therapy, such as
      basal cell carcinoma, may be reasonable clinical targets. The induction of tumour
      necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interleukin
      12 (IL-12) leads to inhibition of IL-5, with animal models demonstrating immune
      deviation away from Th2 immune responses. The observation that several patients
      with hepatitis C infection and eosinophilia showed normalisation of elevated
      eosinophil counts in association with oral imiquimod therapy encourages further
      exploration of the immune modifying properties of this novel molecule. This
      review is focused on the use of imiquimod for the treatment of external genital
      and perianal warts.

PMID- 15991985
TI  - A re-evaluation of zalcitabine.
AB  - Early in the HIV epidemic, zalcitabine (ddC) emerged as a nucleoside analogue
      reverse transcriptase inhibitor (NRTI) alternative to zidovudine (ZDV). However,
      a comparative study suggested ZDV monotherapy provided superior clinical benefit
      in treatment-naive patients with advanced immunodeficiency. Thus, ddC became most
      widely used in those patients no longer benefitting from or intolerant of ZDV. In
      ZDV-failed or -intolerant patients, ddC demonstrated similar benefit (or absence
      of benefit) to ddI monotherapy. In the first clinical end-point study of
      combination therapy, addition of ddC to on-going ZDV in patients substantially
      pre-treated with ZDV resulted in no overall benefit but some clinical advantage
      in a subset of patients with CD4 cell counts of 150 - 300/mm. Furthermore,
      initial studies of ddC, mostly performed in persons with advanced
      immunodeficiency and symptomatic HIV infection, indicated that 10 - 20% of ddC
      recipients developed a treatment-limiting peripheral neuropathy. Based on these
      early trials, a widespread perception that ddC was an antiviral with both limited
      activity and a potentially problematic safety profile evolved. More recent data
      suggest that the role of ddC requires re-evaluation. Indeed, the European
      Medicines Evaluation Agency (EMEA) has recently expanded the licencing claim of
      ddC stating that it "is indicated in HIV-infected adults in combination with
      other antiretroviral agents". The purpose of this short review is to discuss data
      that have shed new light on what in antiretroviral terms is an 'old' drug.

PMID- 15991986
TI  - Pharmacology of the angiotensin II receptor antagonist, eprosartan.
AB  - The non-peptide angiotensin II receptor antagonists represent a new class of
      drugs with demonstrated efficacy in the treatment of hypertension. Eprosartan is
      a potent, orally active AT(1) receptor antagonist which is chemically distinct
      from losartan and other non-peptide angiotensin II receptor antagonists.
      Eprosartan has a high affinity for the angiotensin II AT(1) receptor, but does
      not interact with the AT(2) receptor, adrenergic receptors or other receptors
      involved in cardiovascular regulation. In contrast to most other angiotensin II
      antagonists, eprosartan is a true competitive antagonist of the AT(1) receptor.
      Eprosartan is effective in antagonising the cardiovascular and renal effects of
      exogenous angiotensin II in both experimental animals and humans. Furthermore, it
      is an effective antihypertensive agent when administered to renin-dependent
      hypertension animal models, and in patients with mild to severe hypertension. The
      antihypertensive effect of eprosartan is maintained over a 24-h interval
      following a single dose with no reported dose-dependent adverse side-effects.

PMID- 15991987
TI  - Recent advances in the understanding of the effects of opioid agents on feeding
      and appetite.
AB  - The endogenous opioid system has been implicated in a wide range of homeostatic,
      autonomic and motivational functions, including mediation of food intake. This
      review examines the roles of the three traditional gene-related opioid peptides
      (proopiomelanocortin, proenkephalin, prodynorphin) and the three major opioid
      receptor subtypes and their clones (mu [MOR-1], delta [DOR-1] and kappa [KOR-1])
      in mediating food intake under spontaneous, deprivation, glucoprivic, stressful
      and palatable ingestive situations. The opportunities of both the identified
      selective opioid receptor subtype agonists and antagonists are reviewed with
      respect to food intake, as well as the problems related to crossed affinities and
      neuroanatomical mismatches between the major opioid peptides and their presumed
      receptor subtypes. The cloning of the opioid receptors, together with the recent
      discoveries of a new generation of opioid peptides (orphanin FQ/nociceptin,
      endomorphins), are examined for their presumed modulation of food intake. The
      opportunities created by recent molecular 'knockdown' techniques, primarily the
      use of antisense oligodeoxynucleotides, in creating highly specific and selective
      probes for elucidating specific receptor mediation of different forms of food
      intake, are given specific attention. These new data suggest the role of splice
      variants of opioid receptor clones in differentially mediating different forms of
      food intake, raising the possibility for the further development of precise
      pharmaceutical tools with which to address disorders and deficits related to
      ingestion.

PMID- 15991988
TI  - Ion channel modulators that enhance acetylcholine release: potential therapies
      for Alzheimer's disease.
AB  - Enhancing the release of acetylcholine (ACh) in the brain is one approach to
      increasing neuronal activity, restoring central cholinergic tone and improving
      attention and cognition. ACh release is modulated by both ligand-gated (gamma
      amino butyric acid A receptors/benzodiazepine [GABA(A)/BDZ], nicotinic
      acetylcholine and serotonin, 5-HT3) and voltage-gated (calcium and potassium) ion
      channels. Of the ligand-gated channel modulators, the BDZ receptor (BDZR) inverse
      agonists (beta-CCM, ZK 93426) enhance activity-dependent release in animals,
      whereas S-8510, a partial inverse agonist, and the BDZR antagonist, flumazenil,
      show enhancement regardless of the behavioural state of the animal. Some of these
      agents have undergone limited clinical evaluation for Alzheimer's disease (AD)
      (ZK 93426, flumazenil, S-8510), but their potential anxiogenic liability makes
      their therapeutic use uncertain until more clinical data are available. Within
      the group of nicotinic agonists, ABT-418, though less potent than nicotine and
      epibatidine in promoting ACh release in vitro, was clinically evaluated based on
      its in vivo profile. Its lack of oral bioavailability has limited its
      acceptability, though transdermal administration has been used to circumvent this
      deficiency. Serotonin 5-HT3 receptor modulators have not been advanced for
      clinical evaluation for the treatment of AD. Among the voltage-gated ion channel
      modulators affecting L- or N-type calcium channels, nefiracetam, a nootropic
      agent, also increased ACh release in animal studies. It is currently undergoing
      clinical evaluation for AD, though a need for more potent and brain selective
      calcium channel blockers exists. Potassium channel modulators have been the most
      studied ACh release enhancing agents and several of these compounds (4-AP, 3,4
      DAP, linopirdine) have been clinically evaluated. In AD patients, 4-AP, an A-type
      K+ channel blocker, elicited inconsistent and unremarkable effects. Linopirdine,
      whose enhancement of ACh release correlates with its ability to block M-type K+
      channels, also produced disappointing clinical results, which may have been
      related to its suboptimal pharmacokinetic profile. Further work in this series
      has provided a compound (DMP 543) that should be a more reliable indicator of
      whether a blocker of this ion channel can activate the cholinergic system in man.
      This agent is currently undergoing clinical evaluation for AD.

PMID- 15991989
TI  - The potential application of cyclo-oxygenase type 2 inhibitors to Alzheimer's
      disease.
AB  - In recent years, dramatic progress has been made in the understanding of the
      neurogenetics and neurobiology of Alzheimer's disease (AD). A great deal of
      experimental evidence has accumulated to support the hypothesis that inflammatory
      mechanisms are involved in the pathophysiology of AD. In addition,
      epidemiological studies have revealed that anti-inflammatory medications reduce
      the risk of developing AD. However, long-term use of conventional anti
      inflammatory drugs is associated with significant toxicity which limits their
      potential application to the treatment or prevention of AD. It is believed that
      the inhibition of cyclo-oxygenase type-1 (COX-1) causes much of this toxicity,
      while inhibition of COX type-2 (COX-2), which is induced by inflammatory stimuli,
      may confer the anti-inflammatory effect. COX-2 is also constitutively expressed
      in brain regions preferentially affected in Alzheimer's disease and may be
      directly involved in neuronal cell death. Therefore, selective COX-2 inhibitors
      represent a promising class of drugs for the treatment of AD.

PMID- 15991990
TI  - Treatment of neurodegenerative diseases with neural cell transplantation.
AB  - Neural cell transplantation is an emerging therapy that may provide an effective
      treatment for neurodegenerative disorders. The most extensive work with neural
      transplants has been carried out for Parkinson's and Huntington's diseases.
      However, intensive efforts are also being made for the treatment of other
      neurological indications, such as spinal cord repair, stroke, epilepsy, multiple
      sclerosis (MS), Alzheimer's disease and amyotrophic lateral sclerosis (ALS or Lou
      Gehrig's disease), to name just a few. The major barrier for the successful
      application of cells as therapeutics is achieving long-term survival and
      function. The CNS has proven to be ideal for transplantation, in part because
      immune rejection is attenuated in the CNS compared to peripheral locations.
      However, some form of immunosuppression is desirable for optimal allograft
      survival and required for xenograft survival. This review will focus on the
      challenges of restoring function to something as intricate as the CNS and on the
      limitations imposed by this complexity on any cellular therapeutic.

PMID- 15991991
TI  - Adenosine modulation: a novel approach to analgesia and inflammation.
AB  - Adenosine (ADO) is an endogenous purine nucleoside that functions as an
      extracellular signalling molecule. It is released locally at sites of cellular
      trauma, and acts on specific cell-surface purinergic receptors (termed P1
      receptors) near its site of release to exert its effects. Four subtypes of the P1
      family of G-protein-coupled receptors have been identified and cloned: A1, A2A,
      A2B and A3. A considerable body of evidence, including experimental animal data
      and preliminary clinical reports, indicates that ADO is involved in modulating
      endogenous antinociceptive processes in the brain and spinal cord. ADO analogues
      provide analgesic activity after systemic or spinal administration in a broad
      spectrum of animal pain models. In addition, iv. ADO infusion has shown benefit
      in human pain states. The spinal cord is a key site for ADO-mediated modulation
      of nociception. ADO is well known to act as an inhibitory neuromodulator in the
      central and peripheral nervous system, and it may act to control N-methyl-D
      aspartate (NMDA)- and substance P-mediated events in nociception and central
      sensitisation at the spinal level. ADO is also released at sites of inflammation
      and it exerts anti-inflammatory effects via multiple mechanisms involving several
      cell types. These include effects on neutrophil function, endothelial cell
      permeability, in vivo and in vitro release of tumour necrosis factor (TNF-alpha
      and collagenase expression in synoviocytes. Accordingly, ADO analogues are
      effective in several animal models of inflammation, including the rat adjuvant
      arthritis model. Several therapeutic approaches to pain and inflammation, based
      on mimicking or modulating the effects of endogenous ADO, are currently under
      preclinical and clinical investigation. These include the use of ADO itself, the
      use of direct-acting ADO receptor agonists and the use of agents designed to
      modulate the levels and, therefore, the actions of ADO in the extracellular space
      (ADO kinase (AK) inhibitors). Data emerging in the next several years should
      indicate whether these strategies represent a therapeutically useful new approach
      to analgesia and inflammation.

PMID- 15991992
TI  - The treatment of tuberculosis: current status and future prospects.
AB  - Although a vaccine and effective chemotherapy against tuberculosis (TB) have been
      available for more than half a century, TB was declared a global emergency in
      1993. Current chemotherapeutic regimens are being undermined by lack of resources
      for proper implementation and control, and the emergence of multi-drug resistant
      strains of Mycobacterium tuberculosis. Several new chemotherapeutic agents are
      under development, mainly derived from existing anti-TB drugs or broad-spectrum
      antibiotics. New experimental agents include immunomodulants and drugs directed
      against novel cellular targets.

PMID- 15991993
TI  - Tyrosine kinases in disease: overview of kinase inhibitors as therapeutic agents
      and current drugs in clinical trials.
AB  - Tyrosine kinases, first described as oncogenes, have been shown to play a role in
      normal cellular processes. Aberrations in tyrosine kinase activity lead to
      disease states. For fifteen years it has been postulated that the inhibition of
      tyrosine kinases may have therapeutic utility and the design and testing of
      inhibitors have been major focuses of research and development in both academic
      institutions and pharmaceutical companies. While early research focused on
      developing chemical entities that mimic phosphotyrosine, later research has
      focused on developing competitive adenosine triphosphate (ATP) inhibitors with
      various levels of selectivity on kinase targets. This review focuses on a
      discussion of tyrosine kinases thought to be important in disease, including
      platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular
      endothelial cell growth factor (VEGF), epidermal growth factor (EGF) receptors,
      HER-2 and Src. In addition, the classes of inhibitors designed to affect these
      targets and that have overcome research and development challenges and entered
      clinical trials are discussed. These include isoxazole, quinazoline, substituted
      pyrimidines and indolinone compounds, all of which are in clinical trials or near
      clinical development by SUGEN, Zeneca, Novartis, Pfizer and Parke-Davis. A
      summary of the chemistry and activity of these agents is provided.

PMID- 15991994
TI  - Novel oestrogen sulfamates: a new approach to oral hormone therapy.
AB  - Sulfamate substitution at the C-3 position of the steroid skeleton leads to
      orally active prodrugs of ethinyloestradiol, oestradiol, oestrone, oestriol and
      probably many other natural or synthetic steroidal oestrogens. These compounds
      have higher systemic, but reduced hepatic, oestrogenic activity than their parent
      steroids. The release of the parent oestrogen results from the passage of the
      sulfamates in the erythrocyte compartment through the liver and the systemic
      hydrolysis of the sulfamate ester. Sulfamates may be used to generate natural
      oestrogens, oestradiol and other oestrogens for different types of oral oestrogen
      therapy, e.g., as oestriol for hindered oestrogen or as 17-alpha oestradiol for
      'non-feminising' oestrogen. Oestradiol sulfamate J995 is currently in the initial
      stages of clinical testing. It has per se no oestrogen receptor affinity or
      oestrogenic activity in vitro, i.e., is inactive without hydrolysis. Its oral
      uterotropic activity in rats is approximately 100-times higher than that of
      oestradiol, its hepatotropic activity, however, is only 2- to 3-fold higher than
      oestradiol. Oral oestradiol sulfamate treatment should, therefore, reduce the
      hepatic side-effects seen with conventional oral hormone therapy, while at the
      same time lead to full stimulation of the uterus and the vagina, and suppression
      of gonadotropin. In the rat, orally administered oestradiol is effectively
      extracted from the portal vein and excreted via the bile. In contrast, oestradiol
      sulfamate is present in the circulation at high concentrations, up to 30% of the
      dose. Initially, 98% of this is found in the erythrocyte compartment and only 2%
      in the plasma. Significant oestradiol levels in the blood are recorded during the
      depletion of this pool. Pharmacokinetic and toxicological studies reveal complete
      excretion of the compound and its metabolites. No toxic effects have been seen in
      rats and cynomolgus monkeys at any dose, in spite of the compound's distinct
      oestrogenicity. The evaluation of genotoxicity also yielded negative results.

PMID- 15991995
TI  - The streptogramin antibiotics: update on their mechanism of action.
AB  - Antibiotics of the streptogramin class are an association of two types of
      chemically different compounds, group A molecules and group B molecules, acting
      in synergy. The combination of these molecules generally inhibits bacterial
      growth at a lower concentration than does either the group A or group B molecule
      alone and is often bactericidal against strains of bacteria for which each type
      of molecule alone is only bacteriostatic. The semisynthetic streptogramin
      quinupristin/dalfopristin (RP 59500), the first water-soluble member of this
      class, is under development for the treatment of severe infections caused by
      methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus
      epidermidis, penicillin-resistant Streptococcus pneumoniae, glycopeptide
      resistant Enterococcus faecium, and other organisms. The streptogramins block the
      translation of mRNA into protein. Both group A and group B molecules bind to the
      peptidyl-transferase domain of the bacterial ribosome. The group B molecule
      stimulates the dissociation of peptidyl-tRNA from the ribosome and may interfere
      with the passage of the completed polypeptide away from the peptidyl-transferase
      centre. The group A molecule inhibits the elongation of the polypeptide chain by
      preventing both the binding of aminoacyl-tRNA to the ribosomal A site and the
      formation of the peptide bond. When the two types of molecule are used in
      combination, the binding of the group A molecule alters the conformation of the
      ribosome such that the affinity of the ribosome for the B molecule is increased.
      This accounts, in part or entirely, for the observed synergy. This synergy is
      unaffected by ribosomal modifications conferring resistance to the macrolides,
      lincosamides, and group B molecules alone.

PMID- 15991996
TI  - Retinoid related molecules: new promises against lung and breast cancer.
AB  - Retinoids have long interested cancer researchers due to their well-documented
      antiproliferative and differentiation inducing activities. However, natural
      compounds such as all-trans and 9-cis retinoic acid, as well as related synthetic
      derivatives, show only moderate anticancer activities, while at the same time
      inducing a broad range of undesirable activities. By taking advantage of the
      newly gained understanding in retinoid action and screening large numbers of
      novel molecules, new potent anticancer agents have been discovered that often
      lack typical retinoid side effects. Two of these novel types of molecules,
      referred to here as retinoid related molecules (RRMs), are described, one of
      which effectively kills non small cell lung cancer cells by apoptosis and is
      effective and well tolerated in vivo, while the other one belongs to a class of
      molecules selective for the nuclear receptor, RXR, which promises to be more
      effective and more tolerable than presently used compounds in anti-breast cancer
      adjuvant therapy. These novel molecules demonstrate the potential of novel RRMs
      that vastly outreaches classical retinoids.

PMID- 15991997
TI  - The long-awaited magic bullets: therapeutic human monoclonal antibodies from
      transgenic mice.
AB  - The ability to produce a diverse repertoire of fully human monoclonal antibodies
      (mAbs) may have significant applications to human therapy. This update describes
      the creation of a novel tool for the production of therapeutic human mAbs: a
      mouse strain engineered to produce a large range of human antibodies in the
      absence of mouse antibodies. This strain, XenoMouse, has been generated by the
      introduction of large segments of human immunoglobulin loci, containing the
      majority of the human antibody gene repertoire, into mice deficient in mouse
      antibody production. The mice produce a diverse array of authentic fully human
      IgGkappa antibodies. Upon immunisation with multiple human antigens the mice
      generate large panels of high affinity, antigen-specific fully human mAbs with
      therapeutic activities. XenoMouse-derived hybridomas were shown to be stable,
      producing significant levels of human mAbs. XenoMouse technology represents an
      efficient and reliable tool for the production of therapeutic human mAbs, which
      can accelerate the evaluation and validation of antibody therapy in human
      disease.

PMID- 15991998
TI  - Potential therapeutic applications of fructose-1,6-diphosphate.
AB  - Ischaemia-related tissue injury is the leading cause of death in developed
      countries. Drugs that can reduce ischaemic injury would be beneficial in
      treatment of myocardial infarction (MI), surgical trauma and stroke. Fructose-1,6
      diphosphate (FDP) is a key intermediate in anaerobic glycolysis and is the
      product of the major regulatory enzyme in the pathway (phosphofructokinase).
      Preclinical and clinical data suggest that FDP has substantial cytoprotective
      effects in a variety of ischaemia-reperfusion injury scenarios. Evidence
      indicates that FDP has a direct effect on ATP pools, reduces ischaemia-induced
      tissue damage and has positive inotropic effects on heart function. The clinical
      data suggest that FDP may be a useful drug in a variety of ischaemic and
      inflammatory clinical settings where acute management of tissue injury is
      desired. Potential uses include: iv. administration for the reduction of
      ischaemic injury in sickle cell anaemia, bypass surgery, congestive heart
      failure, myocardial infarction, as well as organ preservation in transplants.

PMID- 15991999
TI  - Antitumour activity of DX-8951f: a new camptothecin derivative.
AB  - DX-8951f is a water-soluble camptothecin analogue with a unique hexacyclic
      structure. Compared to other current camptothecin derivatives, DX-8951f is the
      most effective topoisomerase I (topo I) inhibitor and has the most potent
      cytotoxic activity against various tumour cell lines in vitro. Of particular
      interest is DX-8951f's significant effect on certain tumour cell lines resistant
      to other camptothecin derivatives, as well as on multi-drug resistant variants
      that overexpress P-glycoprotein. In addition, in in vivo xenograft systems using
      nude mice, DX-8951f strongly inhibits the growth of human solid tumours,
      including resistant tumours. Its antitumour effects and resulting life
      prolongation in tumour-bearing mice have also been confirmed in several
      metastasis models. DX-8951f provides greater therapeutic efficacy and broader
      effective dose ranges using multiple injections than with a bolus injection and
      simple intermittent applications. The in vivo effects of the compound are
      superior to those of CPT-11 and SK&F104864, suggesting that DX-8951f is a
      promising therapeutic agent for the treatment of cancer patients. Phase I
      clinical trials are ongoing in Europe, the USA and Japan.

PMID- 15992000
TI  - Zolmitriptan: a new acute treatment for migraine.
AB  - Zolmitriptan is a new oral acute treatment for migraine. It is a selective and
      potent agonist at the serotonin (5-HT)(1B/1D) receptor and was developed to
      improve on the oral bioavailability, tissue selectivity and CNS penetration of
      earlier compounds. Animal studies confirmed that these objectives had been
      attained. In man, zolmitriptan is rapidly absorbed after oral administration,
      with at least 75% of the eventual C(max) reached within 1 h. Oral bioavailability
      is approximately 40%. The elimination half-life of zolmitriptan is approximately
      2.5 h and the primary route of elimination is metabolism, with one of the
      metabolites being pharmacologically active. A consistent 2-h headache response
      rate of 60-70% was observed at doses of 2.5 mg and above. Long-term treatment
      response is high (> 80%) and consistent. In addition, there is evidence from
      electrophysiology in migraineurs that zolmitriptan has a central action not
      shared by sumatriptan. Zolmitriptan is well-tolerated. The nature and incidence
      of the most frequently reported adverse events are similar to those of other 5
      HT(1B/1D) agonists. Long-term zolmitriptan usage was associated with an
      improvement in quality of life. Zolmitriptan is a suitable first-line drug for
      acute treatment for migraine.

PMID- 15992001
TI  - IBC's conference on pulmonary hypertension: new understanding for therapeutic
      development.
AB  - The International Business Communications conference on 'Pulmonary Hypertension:
      New Understanding for Therapeutic Development' was held in San Diego, CA, USA.
      Approximately 100 basic scientists and clinicians from academia and industry
      participated in this highly interactive two-day symposium on pulmonary
      hypertension (PHT). Topics discussed included current clinical therapies and
      novel therapeutic strategies, e.g., nitric oxide, phosphodiesterase (PDE)
      inhibition, prostacyclin synthase expression, endothelin receptor antagonism and
      elastase inhibition.

PMID- 15992002
TI  - IBC's international Conference on Novel Therapeutic Proteins for Oncology (drug
      discovery and development).
AB  - It is estimated that 564,800 Americans will die of cancer in 1998. Even though
      earlier detection and healthier lifestyles may have led to some improvements in
      cancer mortality, new agents are urgently needed to treat incurable cancers. At
      the recent International Conference on Novel Therapeutic Proteins for Oncology, a
      wide range of new agents and strategies for targeting tumour cells were
      discussed. Many of these will be reviewed here.

PMID- 15992003
TI  - Agrp, a novel gene implicated in the control of feeding.
AB  - Rapid progress has recently been made to characterise a new pathway involved in
      the control of feeding behaviour, referred to as the melanocortinergic pathway.
      Studies of the obese phenotype of the yellow mouse mutant (Ay) suggested the
      existence of this feeding circuit for some time, but the precise molecular and
      biochemical regulation was unclear. Through pharmacological and genetic
      approaches, specific melanocortin receptors expressed within the brain are now
      known to play a pivotal role. Since receptor agonists decrease food intake, and
      blocking receptor activity (through antagonists or mutations) increases food
      intake, this pathway is thought to provide a tonic inhibitory effect on food
      consumption. A unique feature of this pathway seems to be the regulation of
      receptor activity by an endogenous protein antagonist, agouti-related protein
      (AGRP). The molecular characterisation and biochemical activity of this gene
      suggest that it plays a role in the regulation of feeding behaviour.

PMID- 15992004
TI  - The therapeutic potential of targeting the cell cycle.
AB  - With the advent of modern molecular genetics, molecular biology and biochemistry
      has come a revolution in oncology drug discovery research. We are rapidly
      developing an increased understanding in the mechanisms driving cellular
      proliferation, transformation, differentiation and metastasis. The hope is that
      from these advances will emerge novel therapeutics that are more specific, more
      efficacious and less toxic than their predecessors. Uncontrolled proliferation is
      a hallmark of a cancer cell. Over the past two decades it has become increasingly
      clear that molecules that directly control cell cycle progression accumulate
      defects during tumourigenesis. These defects can result in the loss of checkpoint
      control and/or the inappropriate activation of the 'drivers' of cell cycle
      progression, the cyclin-dependent kinases (cdks). This review will describe the
      recent advances in our understanding of cell cycle regulation and its relation to
      tumourigenesis, and highlight the potential for the development of novel
      anticancer therapeutics.

PMID- 15992005
TI  - Apoptosis: a novel therapeutic tool?
AB  - Apoptosis is a genetically programmed cell death mechanism that appears to occur
      in all multicellular organisms. It is a normal process that serves to maintain
      cellular homeostasis. However, in many diseases there is a disruption in the
      equilibrium between cell proliferation and cell death that contributes directly
      to the disease. In these cases, a possible therapeutic intervention would be to
      restore the skewed equilibrium by pushing it in the desired direction through the
      use of pharmacological agents or genetic approaches. These observations have
      instigated substantial research in the field of apoptosis, resulting in an
      increasingly detailed analysis of the molecular mechanisms and the sequence of
      events that occur in this cell death pathway. In addition, by trying to
      understand this pathway, several potential therapeutic agents have arisen from
      those used in chemo-, radio-, and cytokine therapy. While these agents have been
      relatively successful, it is rare that their effect is complete. Thus, the search
      continues for a strategy to conquer those cells that are resistant to these
      regimens. Genetic approaches are novel and have been shown to be quite successful
      in several in vitro and animal models. They also tend to have low toxicity. It is
      believed that using a more traditional front-line approach of therapy,
      supplemented by appropriate genetic intervention, will allow substantial
      increases in the efficacy of treatment, while at the same time introducing little
      or no additional toxicity.

PMID- 15992006
TI  - Prospects for bioreductive drug development.
AB  - Bioreductive drugs are inactive prodrugs that are converted into potent
      cytotoxins under conditions of either low oxygen tension or in the presence of
      high levels of specific reductases. The biochemical basis for selectivity relies
      on the ability of oxygen to reverse the activation process and the presence of
      elevated reductase levels in some tumour types. Key criteria for an ideal
      bioreductive drug should include poor activity against aerobic cells, activation
      over a broad range of oxygen tensions and, penetration through the aerobic
      fraction of cells. In addition, the active drug should be capable of killing non
      proliferating cells. Numerous compounds are currently at various stages of drug
      development but Mitomycin C, which is generally considered to be the prototype
      bioreductive drug, is the only one in clinical use today. Of the drugs currently
      being evaluated clinically, tirapazamine has definite clinical activity against a
      variety of solid tumours when used in combination with cisplatin. Other drugs,
      such as EO9 and various nitroimidazoles, have not been impressive in the clinic
      and further development is required to improve properties such as drug delivery
      in the case of indoloquinones. A novel approach to exploiting tumour hypoxia is
      the development of a gene-directed enzyme prodrug therapy (GDEPT) strategy, where
      a gene encoding for a prodrug activating enzyme has been placed under the control
      of a hypoxia responsive promoter sequence. It is generally recognised that
      bioreductive drugs must be directed towards patients whose tumours have hypoxic
      regions or have appropriate enzymological characteristics. In terms of
      identifying tumour hypoxia, there has been considerable progress in the
      development of nitroimidazole based hypoxia markers that can be detected either
      via non-invasive or invasive procedures. Another strategy currently undergoing
      preclinical evaluation is the use of agents that modulate tumour blood flow and
      synergistic effects have been reported between bioreductive drugs and
      photodynamic therapy or inhibitors of nitric oxide synthase for example. The
      development of clinically useful bioreductive drugs depends therefore on the
      expertise of scientists and clinicians with varying backgrounds. The purpose of
      this review is to describe and critically assess recent developments in this
      field, with particular emphasis being placed on drug development and strategies
      aimed at optimising bioreductive drug activity.

PMID- 15992007
TI  - Approaches to multidrug resistance reversal.
AB  - Multidrug resistance (MDR) is characterised by cross-resistance between unrelated
      anticancer drugs and is associated with the overexpression of a membrane bound
      high-molecular weight glycoprotein, named P-glycoprotein, which is able to
      actively expel the drugs out of the cells. In vitro, numerous compounds have
      demonstrated the ability to inhibit the transport activity of P-glycoprotein,
      resulting in enhanced intracellular drug accumulation and MDR reversal. Such
      compounds include drugs of current use in other therapeutic areas, such as
      verapamil, cyclosporin A, quinidine or tamoxifen. Clinical trials have been
      performed on these drugs with the aim of reversing drug-resistance, but their
      toxicity was often too high. Therefore pharmaceutical firms have preferred to
      evaluate either analogues of these drugs, or compounds specifically designed for
      resistance reversal. Drugs that have clearly shown a potential for sensitisation
      of resistant cancers with acceptable toxicity include dexverapamil one of the two
      enantiomers constituting verapamil, valspodar (PSC-833), an analogue of
      cyclosporine A, and original compounds, named VX-710 and GF-120918. Positive
      results have most often been obtained in haematological malignancies (myelomas,
      lymphomas and acute myeloblastic leukaemias), but sometimes also in solid tumours
      (breast and ovarian carcinomas). Randomised Phase III studies are ongoing for
      compounds showing a definite activity in Phase II studies, with the aim of
      analysing the benefits of the combination of an MDR reverter and conventional
      chemotherapy, in terms of patients' survival. However, drug-resistance is a
      multifactorial phenomenon, with MDR constituting only part of it. In addition, a
      rigorous clinical evaluation of MDR will have to be performed, which has not
      always been the case in early trials.

PMID- 15992008
TI  - Combination therapy for HIV: towards long term control of disease progression.
AB  - The difficulty of curing HIV patients with currently available agents has now
      been demonstrated and the model of care has returned to the long-term use of
      antiretroviral therapy. As such, the current minimum standard of care is triple
      drug therapy, with two nucleoside analogues,along with either a protease
      inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRT). Such
      regimens induce long-term virologic suppression in only 50 - 67% cases, so new
      approaches are needed. The most promising of these includes the use of two
      protease inhibitors,particularly in drug-naive patients, with the addition of one
      or two nucleoside analogues. Newer agents that merit further study include
      hydroxyurea,abacavir, adefovir, amprenavir and efavirenz. Their role in clinical
      practice remains to be defined. More complex regimens (including six drugs) are
      also under consideration. Although they may be more effective, long-term
      adherence to therapy may be problematic, and such approaches may be more
      appropriate for short-term use to 'induce' a virologic remission that could then
      be 'maintained' using a much simpler regimen. Preliminary data generated using
      such an approach have been disappointing, but this may relate to the specific
      selection of patients and regimens rather than a basic conceptual flaw with the
      approach itself. Although much progress has been made in the field of
      antiretroviral therapy, there is still a long way to go. The insightful study of
      new combinations of older and newer agents will help us to get closer to our goal
      of long-term control of HIV infection in all patients.

PMID- 15992009
TI  - Synthetic and recombinant antithrombin drugs.
AB  - As the final enzyme in the activation of the coagulation system, the serine
      protease, thrombin, is believed to be an important target for the development of
      new anticoagulant/antithrombotic drugs. Direct thrombin inhibitors are either
      derived from natural sources, such as hirudin or are chemically synthesised, such
      as argatroban. The coupling of hirudin or parts of it with other entities leads
      to novel agents with different pharmacokinetic and pharmacodynamic
      characteristics, such as polyethylene glycol (PEG)-hirudin or the hirulogs. Due
      to the reversible or irreversible inactivation of the enzyme, thrombin inhibitors
      exert strong anticoagulant effects that can be measured in global clotting
      assays. Furthermore, these compounds inhibit thrombin-induced platelet reactions
      and influence other cellular, receptor-mediated actions of thrombin, e.g., on
      vascular cells. Directly acting thrombin inhibitors prevent blood clotting and
      are also capable of inhibiting clot-associated thrombin; however, they do not
      effectively block the further generation of the enzyme. Comprehensive
      experimental studies suggest that thrombin inhibitors may be effective drugs in a
      wide range of intravascular thrombus formation, also including the inhibition of
      vascular restenosis. Recent clinical trials revealed the effectiveness of direct
      thrombin inhibitors in various thrombotic and cardiovascular indications, but
      also a tendency to an increased risk of bleeding complications. At present,
      thrombin inhibitors are the most promising class of drugs for the initial therapy
      of patients with heparin-induced thrombocytopaenia (HIT) or the heparin-induced
      thrombocytopaenia and thrombosis syndrome (HITTS). They are also useful for the
      management of venous thrombosis and for acute ischaemic syndromes as well as for
      invasive procedures. However, with regard to the long-term outcome, a superiority
      of thrombin inhibitors over heparin has not yet been demonstrated. Several
      important issues, such as monitoring, pharmacological antagonism and drug
      interactions will also play an important role in the development of these new
      drugs. Further clinical trials are required to confirm the effectiveness of
      direct thrombin inhibitors in the prophylaxis and treatment of various
      thromboembolic and cardiovascular disorders.

PMID- 15992010
TI  - In vivo antidiabetic drug discovery.
AB  - All of the glucose-lowering agents available today for the treatment of diabetes
      resulted from the in vivo antidiabetic drug discovery approach. This is not
      surprising given the limited understanding of the biochemical basis of diabetes.
      With new developments in the elucidation of the biochemistry and physiology of
      diabetes, along with the ever-increasing number of drug discovery technologies,
      screening tests have shifted from in vivo to in vitro and from a cellular to a
      molecular level. However, there are concerns with this shift because diabetes,
      especially type 2 diabetes, has multiple and independent molecular defects and
      most of the molecular targets currently used await clinical validation. One
      approach (employed by Shaman) has used focused in vivo screening and has been
      successful in avoiding or minimising the drawbacks of in vivo testing, while
      maintaining the benefits. It is hoped that the combined use of in vivo and in
      vitro approaches will generate new breakthroughs in diabetes.

PMID- 15992011
TI  - Novel lentiviral vectors for human gene therapy.
AB  - This review summarises an emerging viral vector system for use in human gene
      therapy - lentiviral vectors. Lentiviral vectors have several advantages over
      existing viral vectors. They can stably express transgenes in non-dividing cells
      in vivo without provoking a significant immune response. They can be produced to
      a high titre and can be pseudotyped with heterologous envelope proteins to confer
      broad tropism. Although not without safety concerns, the properties of lentiviral
      vectors makes them an attractive choice for human gene therapy.

PMID- 15992012
TI  - IBT 9302 (Heparinase III): a novel enzyme for the management of reperfusion
      injury-related vascular damage, restenosis and wound healing.
AB  - IBT 9302 (heparinase III, EC 4.2.2.8), purified from Flavobacterium heparinum,
      selectively cleaves heparan sulfate proteoglycans (HSPGs) from cellular surfaces
      and extracellular matrices. HSPGs serve as binding sites for P- and L-selectins,
      as well as for pro-inflammatory chemokines, such as interleukin (IL)-8. IBT 9302
      reversibly removes these binding sites and inflammatory mediators, thereby
      limiting tissue damage following reperfusion of ischaemic areas by reducing
      leukocyte rolling, adhesion and extravasation. In models of myocardial
      ischaemia/reperfusion injury, infusion of IBT 9302 the time of transport and
      reperfusions, reduces the area of necrosis/area at risk ratios relative to
      vehicle-treated animals. Cardioprotection is accompanied by a reduction in serum
      creatine kinase levels and neutrophil adherence to coronary vessels, and the
      preservation of endothelial relaxation responsiveness to acetylcholine. HSPGs
      also serve as accumulation sites for most growth factors and IBT 9302 limits both
      proliferation and migration of vascular smooth muscle cells to platelet-derived
      growth factor (PDGF), basic fibroblast growth factor (bFGF) and endothelial
      growth factor (EGF). In vivo, the application of IBT 9302 at the time of vascular
      injury significantly reduces arterial medial proliferation. External application
      of IBT 9302 to wounds in a steroid-impaired wound healing model increases tensile
      strength by releasing mitogenic growth factors and HSPGs from the surrounding
      extracellular matrix. Pharmacokinetic studies show a simple monoexponential decay
      following iv. bolus dosing of IBT 9302, with a half-life of 5 - 6 min. The
      majority of [(125)I]-IBT 9302 goes to the liver (60%) and kidneys (25%),
      following iv. dosing. Preliminary toxicology studies in rats following single iv.
      bolus (10 mg/kg) or infusion (10 mug/kg/min) dosing show no untoward effects.
      These results suggest that IBT 9302 may have therapeutic utility in treating
      myocardial ischaemia/reperfusion injury, ischaemic stroke, restenosis or in
      healing diabetic ulcer wounds, by virtue of its ability to selectively cleave
      HSPGs.

PMID- 15992013
TI  - American Association for Cancer Research 1998: promises and prospects for the
      next century.
AB  - The American Association for Cancer Research (AACR) meeting of this year
      highlighted the progress made with farnesyl transferase inhibitors; two compounds
      have now entered Phase I clinical trials: R 115777 (Janssen) and SCH 66336
      (Schering Plough) and several others are nearing clinical testing. Several new
      protein kinase inhibitors from Warner Lambert and Novartis were also discussed.
      Angiogenesis (as well as apoptosis) also featured, with many pharmaceutical
      companies and academic institutions having programmes in this area of cancer
      research. The most promising second generation compounds are
      angiostatin/endostatin and inhibitors of tyrosine protein kinase from the
      vascular endothelial growth factor (VEGF) receptor, including SU 5416 which is in
      clinical trials.

PMID- 15992014
TI  - Therapeutic advantages of third generation antihistamines.
AB  - A third generation of antihistamines is emerging for the treatment of allergic
      rhinitis and chronic urticaria. First generation antihistamines are among the
      most widely used drugs in the world, and provide symptomatic relief from
      allergies and the common cold to millions of patients, mainly in OTC combination
      preparations. Their full potential is limited by the sedation caused by their
      effects on histamine receptors in the brain. Second generation antihistamines
      (terfenadine, astemizole, loratadine and cetirizine), which block peripheral H1
      receptors without penetrating the blood-brain barrier, were developed and
      introduced from 1981 onwards to provide comparable therapeutic benefit without
      the CNS side-effects. Although largely successful in this goal, terfenadine and
      astemizole were found to cause potentially serious arrhythmias when plasma
      concentrations became elevated subsequent to impaired metabolism. It was
      established that the cardiac toxicity was mainly due to the parent drugs. As
      active metabolites could account for most of the clinical benefit, the goal for
      the third generation of antihistamines became to develop therapeutically active
      metabolites that were devoid of cardiac toxicity. The first of these drugs,
      fexofenadine (the active metabolite of terfenadine), was approved in July 1996,
      after an unusually rapid development programme. Its introduction set a new
      standard of safety that led the FDA to request the withdrawal of terfenadine in
      1997 on the grounds that a safer version of an equivalent drug was now available.
      Norastemizole and descarboethoxy loratadine, the metabolites of astemizole and
      loratadine, respectively, are also in clinical development. These offer
      comparable or superior clinical benefits.

PMID- 15992015
TI  - Combined tachykinin receptor antagonists for the treatment of respiratory
      diseases.
AB  - The tachykinins, substance P (SP) and neurokinin A (NK-A), are thought to be key
      players in the process of neurogenic inflammation, which is believed to
      contribute to the pathogenesis of various respiratory diseases. Due to the
      additive nature of the respiratory effects of these sensory neuropeptides,
      inhibiting the effects of tachykinins at both NK1 and NK2 receptors may represent
      a therapeutic advantage for the treatment of asthma, as opposed to receptor
      selective antagonists, which have demonstrated only minimal efficacy to date. A
      number of companies are pursuing small molecule approaches yielding compounds
      with potent, balanced NK1 and NK2 receptor antagonist activities. In allergic
      rhinitis, NK1 receptor antagonism may complement the actions of antihistamines by
      addressing nasal congestion, which is largely unrelieved by these otherwise
      highly efficacious agents. Novel combined H1/NK1 receptor antagonists have been
      developed and may represent a therapeutic option for the treatment of this
      disease.

PMID- 15992016
TI  - Changing therapeutic paradigms in glaucoma management.
AB  - Glaucoma is a family of diseases commonly characterised by progressive optic
      neuropathy with associated visual field deficits for which elevated intraocular
      pressure (IOP) is one of the primary risk factors. For more than a century the
      main goal of glaucoma management has been to eliminate the risk associated with
      elevated IOP. In recent years, accumulating evidence of pressure-independent
      causes of glaucomatous optic neuropathy has led to the recognition that lowering
      IOP alone may often be insufficient for the long-term preservation of visual
      function. An innovative therapeutic approach is now emerging to prevent
      progression of glaucomatous optic neuropathy and preserve vision, irrespective of
      disease aetiology: direct protection of the optic nerve. In addition to reducing
      the risk associated with elevated IOP, this neuroprotective approach will augment
      the overall goal of preserving the optic nerve through direct promotion of
      retinal ganglion cell (RGC) survival and/or prevention of RGC death. Although no
      currently available compounds have been clinically demonstrated to provide
      neuroprotective benefit in glaucoma, recent preclinical studies have shown that
      alpha-adrenergic agonists, such as brimonidine, provide neuroprotective benefits,
      as well as excellent IOP lowering efficacy. In addition, new agents with
      promising neuroprotective utility that are emerging from other studies are now
      being investigated for efficacy in glaucoma. The review discusses recently
      introduced compounds and new drugs in development with regard to their potential
      value in conventional and/or neuroprotective strategies for vision sparing in
      glaucoma.

PMID- 15992017
TI  - New prospects for the treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common inflammatory and destructive arthropathy.
      Current therapies fail to stop joint damage and reduce long-term disability.
      Greater understanding of disease pathogenesis has identified many inflammatory
      mediators as possible therapeutic targets. Novel therapeutic agents, such as
      monoclonal antibodies (mAbs), cytokine receptor-human immunoglobulin constructs,
      recombinant human proteins and antisense oligodeoxynucleotides targeting these
      inflammatory mediators have been tested in rheumatoid arthritis with some
      success. In particular, inflammation can be effectively suppressed using
      anticytokine therapies. However, the ideal treatment for RA, one that is
      immunomodulatory and induces prolonged disease remission after a single course of
      therapy, still eludes us. Strategies aiming to achieve this include TCR peptide
      vaccination and anti-CD4 mAbs, currently in clinical trials in RA.

PMID- 15992018
TI  - Novel approaches to inflammatory bowel disease.
AB  - Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel
      disease (IBD), are chronic, spontaneously relapsing disorders of unknown cause.
      These diseases appear to be immunologically mediated and have genetic and
      environmental influences. Although the cause of these diseases remains obscure,
      the pathogenesis of chronic intestinal inflammation is becoming clearer, due to
      improved animal models of enterocolitis and important advances in immunological
      techniques. Traditional therapy for IBD, although helping to induce and maintain
      disease remission, does little to alter the underlying fundamental disease
      process. New IBD therapy has not developed significantly over the past twenty
      years and includes 5-aminosalicylic acid preparations, corticosteroids and
      immunomodulatory agents, such as azathioprine, 6-mercaptopurine and methotrexate.
      There is, therefore, a need for new, specific disease-modifying therapy and the
      development of such therapy has been hastened by a greater understanding of the
      pathophysiology of IBD. This review examines the most recent novel therapies for
      IBD, with specific emphasis on immunomodulatory and novel anti-inflammatory
      therapies. Recent clinical trials are reviewed, and the potential advances and
      clinical impact that these novel agents may provide are discussed.

PMID- 15992019
TI  - The therapeutic potential of anti-cytokine antibodies in the treatment of chronic
      inflammatory disease.
AB  - The outcome of inflammatory diseases is likely to be dependent upon the relative
      balance of pro- versus anti-inflammatory cytokines. Control of this balance
      through the use of anti-cytokine monoclonal antibodies (mAbs) promises to be an
      effective means of disease therapy. The treatment of rheumatoid arthritis (RA) or
      inflammatory bowel disease (IBD) with anti- tumour necrosis factor alpha (TNF
      alpha) mAb has dramatically ameliorated disease symptoms, indicating that such a
      treatment approach can be highly successful. Similarly, based on animal studies,
      the use of neutralising anti-interleukin (IL)-12 mAb may prove efficacious in a
      number of inflammatory disorders, particularly for IBD.

PMID- 15992020
TI  - Recombinant TFPI and variants: potential implications in the treatment of
      cardiovascular disorders.
AB  - The Kunitz-type proteinase inhibitor, tissue factor pathway inhibitor (TFPI), is
      the only endogenous inhibitor of the tissue factor (TF)-mediated coagulation
      pathway that plays a dominant role in normal haemostasis. TFPI exerts its action
      by binding to factor Xa (FXa) forming a TFPI-FXa complex that then, in a second
      step, binds and effectively inhibits the TF-factor VIIa (FVIIa) complex. Both
      full-length TFPI and chemically modified forms (e.g., truncated, glycosylated or
      phosphorylated TFPI variants) exert various pharmacological effects. The
      anticoagulant and antiplatelet actions of TFPI, its potency in inhibiting
      thrombin and FXa generation, as well as its favourable antithrombotic
      effectiveness seen in different animal models of venous and arterial thrombosis
      make this inhibitor a promising agent that could be potentially useful in several
      clinical indications. The inhibitory action of TFPI is accelerated by heparin.
      Heparin, as well as low molecular weight heparin (LMWH) derivatives, release TFPI
      from the vascular endothelium, an effect which seems to contribute mainly to the
      antithrombotic effectiveness of these drugs. The clinical relevance of TFPI is
      still undefined. Based on the beneficial actions in animal studies, as well as on
      the results obtained in first clinical investigations, TFPI is expected to be
      effective in the treatment of various diseases, such as disseminated
      intravascular coagulation, sepsis, coronary syndromes, stroke and acute
      respiratory distress syndrome (ARD). Further clinical trials should clarify the
      role of TFPI and more importantly define its potential usefulness as a
      prophylactic and/or therapeutic agent.

PMID- 15992021
TI  - New prospects for the treatment of germ-cell tumours.
AB  - Germ-cell tumours are rare tumours of testicular, ovarian and extra-gonadal
      origins. Most are curable by cisplatin-based chemotherapy regimens and surgery.
      Treatment strategy is based on risk factor assessment. The standard cytotoxic
      drugs used for the treatment of this disease are: etoposide, cisplatin, bleomycin
      and ifosfamide. More than 80% of patients are cured by standard treatment. There
      is a dose-response relationship for cisplatin, up to standard 33 mg/m2/week/dose
      intensity. However, further dose escalation has failed to demonstrate an
      increased response. Carboplatin has been shown to be less active than cisplatin.
      Activity has been demonstrated with nitrogen mustard, actinomycin, mithramycin,
      vinblastine, methotrexate and recently with paclitaxel and gemcitabine. Activity
      is questionable with carboplatin, oxaliplatin, lobaplatin, mitomycin and
      anthracyclins. No activity has been reported with vindesine, vinorelbine,
      mitoxantrone, AMSA and topotecan. New treatment strategies are developed in poor
      risk group patients and in patients who fail to achieve complete remission status
      or whom experience recurrent disease. Intensification of chemotherapy is one of
      the tested strategies. Consolidation high-dose chemotherapy with haematopoietic
      stem-cell support is under evaluation. Until now, no trial has proven its
      superiority over standard chemotherapy regimens. Other studies concern the role
      of repeated cycles of high-dose chemotherapy with haematological support.
      Innovative strategies consist of introducing new drugs or new schedules:
      paclitaxel in combination with either ifosfamide and cisplatin or epirubicin,
      short, recycled chemotherapy regimens, use of cisplatin non-cross-resistant drugs
      and different time infusion administration of drugs. The aim of these studies is
      to decrease the residual proportion of treatment failures in this highly curable
      disease, which constitutes a good model for clinical research in cancer
      chemotherapy.

PMID- 15992022
TI  - Cell adhesion molecules and extracellular matrix proteins: potential therapeutic
      applications.
AB  - Adhesion plays a central role as a recognition system, guiding the interaction
      between individual cells, and thereby regulating many biological processes.
      Adhesion can occur via cell-cell or cell-extracellular matrix interactions
      through several major cell adhesion molecule (CAM) families, including selectins,
      integrins, immunoglobulins and cadherins. Recent studies have focused on the
      elucidation of adhesive ligands responsible for the different types of cellular
      adhesion. Significant breakthroughs in CAM research are a result of various
      developments, including the purification of various adhesive proteins from
      different tissue sources and cloned adhesion molecules, the generation of
      specific monoclonal antibodies, the development of functional assays and the
      identification of certain genetic disorders linked to CAM defects. This has led
      to an increased understanding of the importance of CAM as a key therapeutic
      target.

PMID- 15992023
TI  - The pharmacology of bosentan.
AB  - This article describes the pharmacological properties and the overall preclinical
      and clinical profiling of bosentan (Ro 47-0203), a non-peptide endothelin
      receptor antagonist with oral activity. Bosentan is a combined and competitive
      antagonist of both ETA and ETB receptors that is selective for the endothelin
      system. In vitro and in vivo, bosentan potently antagonises the vascular response
      elicited by the endothelins. Preclinical efficacy is demonstrated in a variety of
      pathological models including pulmonary and essential hypertension, renal failure
      of ischaemic and nephrotic origin and cerebral vasospasm following subarachnoid
      haemorrhage. Effects are particularly marked in experimental models of heart
      failure (HF) where bosentan acts as a potent vasodilator that improves overall
      left ventricular performance. After chronic treatment, bosentan also improves
      survival in rats with HF. As a result of the first encouraging clinical results
      that show pulmonary and systemic vasodilation, long-term studies are ongoing in
      the treatment of congestive heart failure (CHF).

PMID- 15992024
TI  - FLOCOR: a new anti-adhesive, rheologic agent.
AB  - FLOCOR (purified poloxamer 188) is a surfactant molecule that represents a new
      class of pharmacological agent. FLOCOR is different in that its activity does not
      depend on high affinity receptor binding but rather on altering the way cells and
      molecules interact with water. Extensive preclinical studies in models of
      vascular occlusive disorders, including circulatory shock, acute stroke, and
      myocardial infarction (MI), suggest that iv. administration of poloxamer 188
      improves microvascular blood flow in ischaemic tissues by inhibiting adhesive
      interactions, lowering blood viscosity and reducing friction along the vessel
      wall. In clinical studies, poloxamer 188 demonstrated statistically significant
      benefits in patients with acute myocardial infarction (AMI) and acute vaso
      occlusive crisis of sickle cell disease. However, these studies were conducted
      with commercial grades of poloxamer 188 that contained nephrotoxic impurities,
      and elevated creatinine was observed in a small percentage of patients. A new
      highly purified version of poloxamer 188 free from impurities has been developed.
      Highly purified poloxamer 188 (trade name FLOCOR) is better tolerated in models
      of renal failure and is anticipated to have a significantly improved therapeutic
      index compared to commercial grade poloxamer 188. Clinical studies are now in
      progress in order to confirm the therapeutic benefits of FLOCOR (purified
      poloxamer 188).

PMID- 15992025
TI  - Functional Genomics Conference: From Identifying Proteins to Faster Drug
      Discovery. March 10-11, 1998, Washington DC, USA.
AB  - The massive effort to sequence the human, mouse, rat, nematode (Caenorhabditis
      elegans), fruit fly (Drosophila), zebra fish, yeast (Saccharomyces cerevisiae),
      fungal (Candida albicans and Aspergillus fumigatus) and several bacterial genomes
      has produced a flood of sequence data. Of the more than 100,000 human genes and
      thousands from other organisms, many partial sequences and several completed
      microbial genomes are available in both public and private databases. However,
      elucidation of function has been achieved for only a very small portion and an
      even smaller percentage have been validated as drug targets. Many companies
      interested in identifying new drug targets also see this bounty of opportunity as
      a major challenge. The raw sequence data say little about the importance of the
      gene and nothing about its potential as a target for drug discovery. Since 1994,
      a new term, 'functional genomics', has entered our lexicon. Functional genomics,
      which in effect is 'high-throughput biology', was originally focused on
      understanding gene function by studying the genes of simpler organisms, such as
      the nematode, C. elegans. As the genes from a number of organisms are highly
      conserved across species, it is believed that studying these basic systems can
      yield valuable insights for drug companies interested in targeting therapeutics
      for the higher organisms. More recently, the approach to functional genomics has
      expanded to include study of gene function in organisms to be targeted for
      therapeutic intervention. This new approach was the theme of the Functional
      Genomics Conference: From Identifying Proteins to Faster Drug Discovery held in
      Washington DC on March 10 and 11, 1998. The organisers (NMHCC) hoped that the
      breadth of the conference topics would reflect the complexities of the modern
      drug discovery process and covered technologies from gene chips, bioinformatics,
      disease models, protein discovery and expression, target validation, high
      throughput screening for genes of unknown function, to integration of the drug
      discovery process. The two day conference placed emphasis on cutting edge
      technology solutions and the development of high-throughput tools to address the
      emerging opportunities in genome-based drug discovery.

PMID- 15992026
TI  - Why are there no new antibiotics?
AB  - Renewed efforts are underway in the pharmaceutical industry to address the
      growing problem of antibiotic resistant pathogens. With this rededication to
      novel antibiotic discovery, new tools and technologies are being deployed to
      understand critical therapeutic intervention points in bacterial metabolism.

PMID- 15992027
TI  - Protein synthesis as a target for antibacterial drugs: current status and future
      opportunities.
AB  - The discovery and development of clinically useful antibiotic classes, such as
      the aminoglycosides, macrolides and tetracyclines, have clearly demonstrated that
      bacterial protein synthesis is a suitable target for drug intervention. New
      information on the binding of classical protein synthesis inhibitors to ribosomal
      RNA provides a rational explanation for their selective action against bacteria
      and also explains why chromosomal point mutations conferring resistance by
      structural changes at the target site are relatively rare in the majority of
      bacteria. These principles will be helpful when considering strategies for the
      screening or design of novel protein synthesis inhibitors that could be developed
      as new antibiotics. Recent progress in the discovery and development of bacterial
      protein synthesis inhibitors is illustrated by consideration of the
      glycylcyclines, ketolides, oxazolidinones and streptogramins.

PMID- 15992028
TI  - Novel anti-staphylococcal targets and compounds.
AB  - Many antimicrobial drugs have become less effective at combating infectious
      diseases, and experts in the field are concerned about the possibility of a 'post
      antibiotic era' for some clinically important pathogens, particularly
      staphylococci. In our hospitals, nosocomial infections due to vancomycin
      resistant enterococci have emerged, and there are concerns that the same
      resistance pattern may evolve in methicillin-resistant Staphylococcus aureus
      (MRSA). Examples from three main areas addressed to prevent this scenario are
      discussed: (i) screening of isolated biochemical targets and intact bacteria
      using high-throughput screening technologies, (ii) modifying existing compound
      classes like quinolones and glycopeptides to create more powerful compounds
      overcoming pathogen resistance and (iii) introduction of completely new classes
      of antibiotics.

PMID- 15992029
TI  - Application of combinatorial chemistry to antimicrobial drug discovery.
AB  - The emergence of pathogens resistant to currently available treatments is seen as
      a public health crisis. Since few new classes of antimicrobial drugs have been
      developed in the last two decades, it is becoming increasingly probable that
      healthcare providers will be faced with infections for which no chemotherapeutic
      agent is available. A renewed emphasis is being placed on employing the most
      advanced drug discovery technologies in the development of new antimicrobials.
      The recently introduced technologies of combinatorial chemistry offer new sources
      of chemical diversity, as well as methods with which to produce and rapidly test
      them. In the last few years, many groups have adopted a number of approaches in
      order to apply combinatorial chemistry to antimicrobial drug discovery. These
      combinatorial strategies, and the manner in which they are used to develop new
      screening formats or to identify new chemical leads are, reviewed.

PMID- 15992030
TI  - The therapeutic potential of monoclonal antibodies against respiratory syncytial
      virus.
AB  - Attempts to develop a vaccine against respiratory syncytial virus (RSV), the
      major cause of lower respiratory tract disease in infants and young children,
      have been unsuccessful. Passive immunisation with antibody to RSV has been found
      to be an effective alternative method for prophylaxis. The product currently in
      use for RSV passive immunisation, a preparation of purified human IgG containing
      virus-neutralising activity, requires monthly iv. infusions. Monoclonal
      antibodies (mAbs) are currently under development as an alternative means of
      treatment that would require lower doses. The first such mAb was recently
      approved for RSV prophylaxis in the USA. The mucosal delivery of antibodies is
      also effective and a mAb nose drop treatment for immunoprophylaxis is under
      development. The potential of passive immunisation for the treatment of existing
      RSV infections is not clear. Antibody treatment following infection clearly
      suppresses viral replication but it may not reduce disease once inflammatory
      processes have been initiated.

PMID- 15992031
TI  - Molecular basis for the antiviral and anticancer activities of unnatural L-beta
      nucleosides.
AB  - As a general rule, enzymes act on only one enantiomer of a chiral substrate and
      only one of the enantiomeric forms of a chiral molecule may bind effectively at
      the catalytic site, displaying biological activity. In recent years, some
      exceptions have been found among viral and cellular enzymes involved in the
      synthesis of deoxynucleoside triphosphates and in their polymerisation into DNA.
      Examples are: herpes virus thymidine kinases, cellular deoxycytidine kinase and
      deoxynucleotide kinases, human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase, hepatitis B virus (HBV) DNA polymerase and, to a lesser extent,
      some cellular DNA polymerases. The lack of enantioselectivity allows herpes
      simplex virus (HSV) thymidine kinase and cellular deoxycytidine kinase to
      phosphorylate the unnatural L-beta-enantiomers of D-thymidine and D
      deoxycytidine, respectively, or of their analogues to monophosphate. This
      phosphorylation represents the first and often the rate-limiting step of their
      activation to triphosphates. The L-triphosphates can then exert antiviral (anti
      HSV, anti-Human cytomegalovirus, anti-HIV-1, anti-HBV) and anticancer activities.
      Although only one L-nucleoside (3TC) has so far gained United States of America
      Food and Drug Administration (USA FDA) approval for clinical use against HIV-1,
      other L-enantiomers of nucleoside analogues, which have shown antiviral or
      anticancer activity in cell cultures are in clinical trials. Their resistance to
      enantioselective enzymes, such as thymidine phosphorylase, thymidylate synthase,
      (deoxy)-cytidine and dCMP deaminases, and their lower affinity for the
      mitochondrial thymidine kinase can ensure a higher selectivity and lower
      cytotoxicity with respect to those exerted by their corresponding natural D
      enantiomers and might be exploited to solve problems arising during chemotherapy,
      such as metabolic inactivation, cytotoxicity and drug-resistance.

PMID- 15992032
TI  - Applying genomics tools to identify therapeutic targets for asthma.
AB  - Asthma is a chronic inflammatory disease of the airways, the susceptibility to
      which is strongly influenced by genetics. Genomics, the study of the human
      genome, is redefining the process for rapidly identifying novel therapeutic
      targets for asthma and other diseases. One approach is to search for
      polymorphisms in genes that increase susceptibility to the disease in order to
      identify genes and cellular pathways relevant to the disease process. In asthma,
      for example, regardless of the genetic factors that contribute to susceptibility,
      good drug targets could be found that affect epithelial integrity, allergic
      response, and the recruitment or activity of inflammatory cells. Such targets may
      consist of proteins that are specifically expressed in certain cell types,
      proteins whose expression is regulated during the disease process or proteins
      involved in the destructive process. This review discusses some of the genomics
      tools that can be used to identify new molecular targets, which in turn are
      useful in screening for novel compounds likely to affect diseases such as asthma.

PMID- 15992033
TI  - Saquinavir-soft gel: establishing saquinavir in HAART regimens.
AB  - The initial formulation of the HIV protease inhibitor (PI) saquinavir (SQV) in
      hard gel capsules (Invirase) demonstrated significant clinical benefit in double
      and triple combination regimens in comparative studies. However, pharmacological
      limitations of this preparation resulted in fewer patients achieving optimal
      treatment responses than observed with other PIs. Changes in formulation and
      dosing to a new soft gelatin capsule formulation of SQV (SQV-SGC, Fortovase
      result in an average 8-fold increase in SQV exposure with SQV-SGC. Data from
      clinical trials indicate that this enhanced plasma exposure translates into more
      potent antiviral activity, with small comparative studies suggesting activity to
      be similar to other available PIs in triple therapy highly-active antiretroviral
      therapy (HAART) regimens. Additionally, SQV-SGC appears to be an excellent
      candidate for PI combination use. SQV-SGC appears well-tolerated with a low
      incidence of mainly gastrointestinal side-effects. The lower affinity to P450
      isozymes of SQV means that the incidence of drug interactions is low, indeed
      probably lower than with other approved members of this class. Current obstacles
      to SQV-SGC's widespread use include only limited, short-term bid dosing data
      (outside of combination with ritonavir) and the pill burden of 18 capsules per
      day.

PMID- 15992034
TI  - Low molecular weight heparin in acute stroke.
AB  - Potential therapeutic strategies in acute ischaemic stroke include reperfusion,
      prevention of thrombus extension and rethrombosis and neuroprotection. Heparins
      inhibit thrombin and factor X and therefore may have useful effects on arterial
      and venous thrombosis; they are effective in the prevention and treatment of deep
      vein thrombosis (DVT) and pulmonary embolism (PE) and in the prevention of
      myocardial infarction (MI) in patients with unstable angina. Low molecular weight
      heparins (LMWHs) and heparinoids are known to be more effective and have a safer
      profile than unfractionated heparins in patients with venous thromboembolic
      disease and coronary artery disease. However, their role in acute ischaemic
      stroke is less clear. The very large International Stroke Trial found that
      unfractionated heparin had no overall benefit in ischaemic stroke, whilst causing
      significant intracranial haemorrhage. A number of Phase II and III trials of LMWH
      have been assessed in acute ischaemic stroke. It remains unclear whether these
      agents are effective and safe in acute ischaemic stroke although they do reduce
      the risk of DVT and PE. A systematic review is now required in order to assess
      the safety and efficacy of LMWH in acute stroke.

PMID- 15992036
TI  - 17th Scientific Meeting of the International Society of Hypertension.

PMID- 15992035
TI  - Summary of the 34th annual meeting of the Drug Information Association.
AB  - A variety of issues relating to clinical aspects of drug development were
      discussed at the 34(th) annual meeting of the Drug Information Association. Among
      the topics covered at this conference were the following: 1, development of CNS
      compounds; 2, the Common Technical Document (CTD); and 3, labelling of drugs for
      use in pregnancy. Issues surrounding the development of CNS compounds were
      discussed by regulatory authorities from the USA and Europe. In almost all
      aspects covered, the regulatory requirements for approval in Europe appear to be
      consistent with those in the USA. Efforts aimed at developing a CTD are ongoing
      under the auspices of the ICH. The goal of this effort is to develop a common
      technical information package that can be submitted to regulatory authorities in
      the USA, the EU and Japan. It is recognised, however, that a number of sections
      of regulatory submissions will remain outside of the CTD. New initiatives in the
      labelling of drugs for use in pregnancy in the USA were reviewed. These efforts
      are being led by the Pregnancy Labeling Task Force of the USA FDA. The overall
      goal of this effort is to more clearly define by labelling, the relative risks of
      pharmaceutical agents that must be administered to pregnant women.

PMID- 15992037
TI  - 58th Annual Meeting of the American Diabetes Association.
AB  - The annual meeting of the American Diabetes Association highlighted considerable
      progress in the field. Prominent presentations focused on a number of new
      emerging therapeutics, as well as new avenues of research that may provide
      greater insight into the aetiology of the disease. This update provides coverage
      of some of the more interesting portions of the meeting.

PMID- 15992038
TI  - Towards engineered polyketides.
AB  - Rapid advances have been made over the past 10 years in the identification of the
      biosynthetic machinery that carries out the biosynthesis of polyketide natural
      products. Many such compounds are used in various therapeutic areas, including
      antibacterials, anticancer, antifungals and cholesterol lowering. It is now
      possible to alter the biosynthetic machinery to produce radically altered
      structural analogues that are not accessible by conventional technologies, such
      as total synthesis or semi synthesis. The most rapid progress has been achieved
      in the antibiotic field through the production of a large number of novel
      erythromycins.

PMID- 15992039
TI  - Lectins: from basic science to clinical application in cancer prevention.
AB  - Many physiological functions are attributable to lectin-carbohydrate
      interactions. Lectins are currently being studied for their ability to destroy
      tumour growth by binding to specific carbohydrate motifs on cancer cells. Cell
      surface molecules, including growth factor receptors are often glycosylated, and
      lectins may act by binding to these. Certain lectins effect the proliferation of
      intestinal epithelial cells. This effect is cell-type and lectin specific and
      occurs in the intestine of intact animals, in human colonic explants and
      colorectal cancer cell lines. Lectins present in mammalian tissue are involved in
      cell-matrix adhesion, differentiation, lymphocyte circulation and
      immunomodulation. Mammalian lectins contribute to detection, diagnosis and
      prognosis of tumour cells, and can be targeted for therapy. New lectins of plant
      and mammalian origin that have one or more of these functions are currently being
      developed as tools that could be used to target tumour cells.

PMID- 15992040
TI  - Recombinant toxins in haematologic malignancies and solid tumours.
AB  - Recombinant toxins constitute a new modality for the treatment of cancer, since
      they target cells displaying specific surface-receptors or antigens. They are
      fusion proteins, which contain toxin and ligand regions, and are produced in
      Escherichia coli. The ligand may be a growth factor or a fragment of an antibody,
      and the toxin is usually one of the two bacterial toxins: Pseudomonas exotoxin
      and diphtheria toxin. Compared to the earlier generation chemical conjugates of
      ligands and toxins, recombinant toxins have many advantages, including
      homogeneity with respect to the connection between the ligand and toxin, ease and
      yield of production and small size. A variety of chemotherapy-resistant
      haematologic and solid tumours have been targeted with recombinant toxins, and
      clinical trials with many of them have recently demonstrated their effectiveness.
      Moreover, their unwanted toxic effects are different from those of most
      chemotherapeutic agents, supporting the expectation that they can be combined
      with existing modalities to improve the clinical resources available to treat
      cancer in humans.

PMID- 15992041
TI  - The potential of retro-inverso peptides as synthetic vaccines.
AB  - Retro-inverso peptides, also known as all-D-retro or retro-enantio peptides, are
      composed of D-amino acids assembled in the reverse order from that of the parent
      L-sequence. Since the orientation of the side-chains in a retro-inverso analogue
      is very similar to that in the parent L-peptide, this leads to a high level of
      antigenic cross-reactivity between the two peptides. The potential of retro
      inverso peptides as synthetic vaccines has been investigated in the case of foot
      and-mouth disease. A single inoculation of retro-inverso peptide corresponding to
      residues 141-159 of the VP1 protein of foot-and-mouth disease virus induced
      longer-lasting and higher antibody titres in immunised animals than the
      corresponding L-peptides. The antibodies cross-reacted strongly with virus
      particles and with L-peptides and conferred substantial protection in guinea-pigs
      challenged with the cognate virus. Retro-inverso peptides have considerable
      potential as synthetic vaccines, since their increased resistance to proteases
      may overcome one of the major drawbacks of classical L-peptide vaccines.

PMID- 15992042
TI  - Cancer vaccine development.
AB  - A new era involving the evaluation of recombinant cancer vaccines has begun with
      the concurrent emergence of insights and technologies in the fields of molecular
      biology and immunology. These advances include: The identification and cloning of
      an array of genes associated with the neoplastic process, such as oncogenes,
      suppressor genes, genes encoding oncofoetal antigens and tissue-lineage
      determinants. The development of a variety of viral and bacterial vectors to
      deliver and present gene products. The identification of numerous T-cell
      costimulatory molecules and an understanding of their mode of action. The cloning
      and analysis of the modes of action of an array of cytokines and other
      immunomodulatory molecules. More sophisticated knowledge of the mode(s) of
      antigen presentation and T-cell activation. One current challenge in cancer
      therapy is the delineation of strategies toward the rational design and
      implementation of recombinant vaccines that will be of therapeutic benefit to
      cancer patients and/or members of groups at high risk for specific neoplasias.
      Numerous concepts are emerging in this regard. The study of immunologic
      intervention using laboratory animal models demonstrates that no one approach
      will prevail for all cancer types or, perhaps, for the various stages of the
      neoplastic process of a given tumour type. The immunological role(s) of CD8+,
      CD4+, natural killer and other cell types, as well as the roles of antibodies,
      must all be taken into consideration. This article reviews some of the strategies
      currently undergoing evaluation toward the development of recombinant vaccines
      for several carcinoma types.

PMID- 15992043
TI  - Block copolymeric biotransport carriers as versatile vehicles for drug delivery.
AB  - This review describes block co-polymer-based systems that are used in drug
      delivery. The main focus is on amphiphilic block co-polymers, the application of
      which modifies the pharmacological performance of various classes of drugs and is
      attracting more and more attention. The two main reasons for this are the high
      tendency of block co-polymer-based drug formulations to self-assemble and the
      flexibility of block co-polymer chemistry, which allows precise tailoring of the
      carrier to virtually any chemical entity. The combination of these and some other
      features makes it possible to adjust block co-polymer-based drug formulations to
      achieve the most beneficial balance in their biological interactions
      (biotransport), with systems that control drug removal from the body and those
      that are responsible for drug therapeutic activity. The following major aspects
      are considered: The role of physical properties of formulations in their
      pharmacological performance. The chemistry and physico-chemistry of block co
      polymers and structure-function relationships in these systems. Examples
      describing the effects of biotransport systems on drug transport and activity in
      cells and some results on their in vivo applications with various drugs.

PMID- 15992044
TI  - QS-21: a water-soluble triterpene glycoside adjuvant.
AB  - QS-21 is a purified immunological adjuvant derived from a natural source, the
      bark of the tree Quillaja saponaria. It is a water soluble triterpene glycoside
      with amphiphilic character that can be mixed with a soluble antigen in a fully
      soluble vaccine formulation or combined with emulsion or mineral salt adjuvants.
      QS-21 has been shown to enhance antibody and cell-mediated immune responses to
      subunit antigens, as well as DNA vaccines in animal models. It acts as an
      immunostimulatory adjuvant, eliciting production of immunomodulatory cytokines,
      and not as an antigen depot. QS-21 is currently under clinical evaluation with
      various vaccines. This includes a Phase II evaluation of a QS-21 adjuvanted
      pneumococcal polysaccharide vaccine and a Phase III evaluation of a QS-21
      adjuvanted GM2-KLH (ganglioside GM2 vaccine) immunotherapeutic product for
      melanoma. At present, more than 1600 individuals have received vaccines
      containing QS-21 adjuvant. In most studies, QS-21-containing vaccines have been
      well-tolerated. No serious adverse events have occurred.

PMID- 15992045
TI  - The drug delivery and biomaterial attributes of the ATRIGEL technology in the
      treatment of periodontal disease.
AB  - Two new products, ATRIDOX Periodontal Treatment and ATRISORB Guided Tissue
      Regeneration (GTR) Barrier have been evaluated as therapies for periodontal
      disease. Both products are based on the unique ATRIGEL technology. The system
      consists of a solution of a resorbable polymer in a biocompatible carrier. On in
      vivo administration, the polymer undergoes a phase change from a liquid to an in
      situ formed implant. Being in liquid form, it initially provides the advantage of
      in vivo placement by simple means, such as syringes to form implants at the site
      of use. The system is biocompatible and has the capability of serving as a
      biomaterial and a drug delivery system. The bioabsorption rates of various
      polymers and the release rates for a wide variety of drugs ranging from simple
      organics to proteins and peptides are tailored to the desired indication. Release
      periods ranging from one week to four months have been achieved with one month
      being the most often desired. For these reasons the ATRIGEL system is being
      applied to a number of medical applications ranging from site and systemic
      oncology to post-operative pain control and bone regeneration using growth
      factors. However, its most visible application to date has been in the
      development of a pipeline of products for the treatment of periodontal disease,
      which is the focus of this paper.

PMID- 15992046
TI  - Recent advances in our understanding of protein conformational stability from a
      pharmaceutical perspective.
AB  - The marginal conformational stability of proteins has made them in some cases
      less than ideal candidates for pharmaceutical agents. Recent progress in our
      understanding of protein structure and stability has provided the opportunity to
      design the desired degree of stability into protein drug candidates.
      Modifications such as the optimisation of interior side-chain packing, the
      introduction of new ion-pairs, as well as the design of stabilising disulfide
      bridges and ligand binding sites, all offer the opportunity to produce proteins
      with enhanced stability properties.

PMID- 15992048
TI  - NMDA antagonists for stroke and head trauma: current status.

PMID- 15992047
TI  - The therapeutic utility of Interleukin-11 in the treatment of inflammatory
      disease.
AB  - Interleukin-11 (IL-11) is a pleiotropic cytokine that exhibits anti-inflammatory
      and mucosal protective effects in a variety of animal models of acute and chronic
      inflammation, such as mucositis, inflammatory bowel disease and autoimmune joint
      disease. This reduction in inflammation and epithelial damage is mediated in part
      through effects of recombinant human (rh) IL-11 on macrophage effector function
      and epithelial cell growth. In vitro studies indicate that rhIL-11 inhibits
      tumour necrosis factor (TNF)-alpha, IL-1beta, IL-12, IL-6, and nitric oxide
      production from activated macrophages. Analysis of the effects of rhIL-11 on
      transcription factors that activate pro-inflammatory cytokines demonstrate that
      the level of induced nuclear factor kappa B (NF-kappaB) binding activity in the
      nucleus of rhIL-11-treated peritoneal macrophages is significantly reduced.
      Studies of normal intestinal epithelial cells indicate that rhIL-11 reduces the
      rate of cellular proliferation. Analysis of cell-cycle progression demonstrates
      that growth inhibition of epithelial cells by rhIL-11 correlates with delayed
      entry into S phase and suppression of pRB phosphorylation. IL-11 also protects
      intestinal crypt stem cells from radiation- or chemotherapy-induced insults. Such
      immunomodulatory and epithelial activities may contribute to the protective
      effects of this cytokine and support the clinical utility of rhIL-11 in the
      treatment of mucositis, as well as a variety of chronic inflammatory diseases,
      such as Crohn's disease and rheumatoid arthritis.

PMID- 15992049
TI  - Mycophenolate mofetil (Cellcept).
AB  - Mycophenolate mofetil (MMF) is a new immunosuppressive drug designed to inhibit
      inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the purine
      synthesis pathway of lymphocytes. IMPDH is crucially important for the
      proliferative responses of human T- and B-lymphocytes. Therefore, inhibition of
      IMPDH leads to selective lymphocyte suppression. Following successful testing in
      different in vitro and animal models, MMF entered clinical trials, where it has
      been used in combination with cyclosporin and steroids. MMF has rapid and
      complete absorption following oral administration. Pilot studies suggested a
      significant reduction in the incidence of rejection at doses of 1-3 g/day. These
      data led to the initiation of 3 pivotal trials, in which MMF was compared against
      different standard immunosuppressive protocols. Nearly 1500 patients were
      enrolled in these 3 randomised, double-blind, multicentre studies of the addition
      of MMF to standard immunosuppressive protocols for the prevention of acute renal
      allograft rejection. After six months, the rate of biopsy-proven rejection was
      significantly reduced. The adverse event profile resembles that of triple therapy
      with azathioprine: primarily involving the gastrointestinal (GI) tract, the
      haematopoietic system and the occurrence of opportunistic infections. MMF affords
      improved immunosuppressive therapy following renal, and probably other solid
      organ, transplantation. It is licensed for the prevention of acute renal
      allograft rejection in most countries around the world.

PMID- 15992050
TI  - Olpadronate: a new amino-bisphosphonate for the treatment of medical
      osteopathies.
AB  - Olpadronate is a nitrogenated bisphosphonate. Although it shares the therapeutic
      and pharmacological properties of pamidronate and alendronate, it has a greater
      dosage amplitude, more predictable effects and a greater digestive tolerability
      than other bisphosphates. Therefore, it may be more appropriate in the treatment
      of medical osteopathies, by both oral and parenteral routes of administration.
      According to various experimental and human models, the pharmacological potency
      of olpadronate is 5- to 10-times higher than that of pamidronate and close to
      that of alendronate. The two methyl groups bound to the nitrogen atom give the
      compound a high water solubility, which is about 8-times higher than that of the
      two other bisphosphonates. The lack of a terminal amino group in the side-chain
      of the molecule and the absence of crystallised forms of the compound in the
      digestive tract (due to its high water solubility) may avoid the potential for
      inducing oesophageal and gastrointestinal side-effects. These features may
      explain the high tolerability reported after the administration of doses of
      olpadronate (by the oral route) up to 5- to 10-times higher than the maximum
      tolerated dose of alendronate in Paget's bone disease and bone metastases, thus
      widening the possibilities for its clinical usage. In addition, initial
      pharmacokinetic studies suggest that olpadronate's oral bioavailability would fit
      into a confidence range of 2-4%, which contrasts with the erratic absorption
      shown by other highly potent bisphosphonates. The clinical efficacy demonstrated
      in preliminary studies in Paget's bone disease (including ultra-short
      treatments), and also in single-dose iv. therapy of hypercalcaemia of
      malignancies, renders olpadronate among the most promising bisphosphonate
      compounds, with potential use in the treatment of a variety of bone-involving
      diseases, such as osteoporosis, malignancies and rheumatoid arthritis.

PMID- 15992051
TI  - 98th General Meeting of the American Society for Microbiology. May 17-21, 1998;
      Atlanta, GA.
AB  - The 98th General Meeting of the American Society for Microbiology was held from
      May 17-21, 1998, in Atlanta, Georgia and was attended by well over 10,000
      scientists. The theme of antibiotic resistance dominated the meeting with
      numerous presentations on resistance mechanisms, new targets and potential
      antimicrobial agents. Many new insights into the understanding of microbial
      physiology were provided. Microbial genomics was shown to be revolutionizing the
      way in which scientists can probe and explore bacteria and fungi.

PMID- 15992052
TI  - FEBS meeting 1998, July 5-10, Kopenhagen.

PMID- 15992053
TI  - The role of COX-2 in intestinal cancer.
AB  - Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis, is
      transcribed from two distinct genes. COX-1 is expressed constitutively in most
      tissues whereas COX-2 is induced by a wide variety of stimuli and was initially
      identified as an immediate-early growth response gene. In addition, COX-2
      expression is markedly increased in 85-90% of human colorectal adenocarcinomas
      while COX-1 levels remain unchanged. Several epidemiological studies have
      reported a 40-50% reduction in the risk of developing colorectal cancer in
      persons who chronically take non-steroidal anti-inflammatory drugs (NSAIDs) such
      as aspirin, which are classic inhibitors of COX. Genetic evidence also supports a
      role for COX-2, since mice null for COX-2 have an 86% reduction in tumour
      multiplicity in a background containing a mutated APC allele. These results
      strongly suggest that COX-2 contributes to the development of intestinal tumours
      and that inhibition of COX is chemopreventative. It is hoped that the
      chemopreventative effects of NSAIDs will be enhanced by the recent development of
      COX-2-specific inhibitors.

PMID- 15992054
TI  - The treatment of advanced colorectal cancer with interferon-alpha: a review.
AB  - Colorectal cancer (CRC) is one of the most common malignancies in the western
      world. The majority of patients who develop this tumour will ultimately die from
      metastatic disease. The fluorinated pyrimidine 5 fluorouracil (5-FU) is at
      present the most active drug available for first-line therapy of this disease.
      Randomised studies have consistently demonstrated a survival advantage from early
      treatment with 5-FU in advanced CRC, which can be achieved without deterioration
      in quality of life. Despite over 30 years of use, the optimal 5-FU schedule
      remains controversial with a wide range of response rates reported in the
      literature. Single agent activity is in the order of 10-11%. In an attempt to
      improve response rates, modulation of 5-FU with a variety of agents has been
      intensively investigated. This article examines the role of interferon-alpha in
      the treatment of advanced CRC.

PMID- 15992055
TI  - Immunological manipulation of body composition.
AB  - Hormonal growth promoters (e.g., growth hormone [GH], beta-adrenergic agonists,
      steroids), which improve growth rate and/or lean:fat ratios in the carcass, have
      received considerable adverse publicity and are either banned or have no licence
      for their use in the EC. This has led to the development of a number of
      techniques, involving the use of antibodies, aimed at regulating metabolic
      processes involved in determining growth and body composition. A different
      approach to the problem of excess fat deposition involves the use of antibodies
      directed against the plasma membranes of adipocytes in order to elicit their
      destruction and thereby limit the capacity for fat storage. This technique has
      been demonstrated in rats, sheep and pigs in both passive and active immunisation
      techniques. This promising approach is, however, limited by the lack of a
      commercially suitable vaccine. The identification of individual membrane proteins
      that are antigenic has been achieved and this affords the prospect of producing
      recombinant DNA-derived vaccines. Whether these new approaches will be perceived
      as acceptable to the general public remains a serious concern and a potential
      limitation to their development as many would-be sponsors withdraw their support
      for research in these areas.

PMID- 15992056
TI  - Successful vaccination for Lyme disease: a novel mechanism.
AB  - Two vaccines are on the horizon for the prevention of Lyme disease, the most
      common vector-borne illness in the US and Europe. This review describes the
      pathogenesis and clinical illness of Lyme disease, as well as the sequence of
      events that led to the development of these novel vaccines. The results of the
      most recent Phase III human trials are reported.

PMID- 15992057
TI  - Caspases in apoptotic death.
AB  - Caspases are the central mediators of normal and pathological apoptotic death.
      They are cysteine proteases that cleave after aspartic acid. The inactive pro
      enzymes are proteolytically processed and activated through mechanisms of
      recruitment to signalling complexes, upstream activator caspases or
      autoactivation. Many amplifying cascades exist in caspase activation pathways
      that are evolutionarily conserved. The human caspase family contains at least 10
      members which form 3 groups based on substrate specificity, proteolytic targets
      and functional actions. The crystal structure has been solved for members from
      two of these groups with inhibitory peptides bound in the active site. These
      structures have allowed tremendous insight into mechanisms of catalysis,
      substrate binding and substrate specificity. Enlightened knowledge of enzyme
      substrate interactions has led to the design of many inhibitors that are active
      in animal models of caspase-mediated cell death. Testing in animal models should
      lead to drugs for therapeutic intervention in the many human diseases
      characterised by excessive apoptotic cell death.

PMID- 15992058
TI  - Antidepressants in the elderly: a review.
AB  - The elderly constitute a growing proportion of our population for whom depression
      represents a significant problem. The choice of antidepressants available to the
      clinician is huge, and this article reviews the available literature on this
      important subject to facilitate evidence-based treatment decisions.

PMID- 15992059
TI  - Applying proteomics to drug discovery.
AB  - Proteomics is a technology that has come to prominence over the last few years
      largely as a result of the advances that have been made in the equipment and
      software associated with the performance and analysis of two dimensional (2D) gel
      electrophoresis. With this technique it is now possible to resolve and identify
      proteins on 2D gels with a high degree of reproducibility and sensitivity. This
      facilitates the detection and quantification of thousands of proteins from
      complex biological samples in a single analysis and, more significantly, the
      comparison of these data accurately and reproducibly between samples. Thus,
      qualitative and quantitative assessments of changes are possible between the
      healthy and diseased state, in the presence and absence of drug, or between
      responders and non-responders. The added ability of carrying out such analysis at
      a high throughput opens up the possibilities for using proteomics to great effect
      throughout the drug discovery process. This review outlines the proteomic process
      and indicates areas where its potential has begun to be realised.

PMID- 15992060
TI  - The therapeutic potential of PD156707 and related butenolide endothelin
      antagonists.
AB  - Plasma concentrations of the peptide endothelin (ET) are elevated in several
      cardiovascular diseases. Animal studies suggest that activation of ET receptors
      may contribute to the increase in vascular resistance and remodelling of
      cardiovascular tissues that are characteristic of these pathologies. Antagonists
      of these receptors may therefore have important clinical potential. PD156707
      (Parke-Davis) is one of a series of novel, orally-active butenolide endothelin
      antagonists and is highly selective for the ETA receptor. In man, this subtype
      mediates the profound vasoconstrictor effects of the ET peptides, and blockade of
      the ETA receptor may therefore produce beneficial vasodilatation. The advantage
      of selective ETA receptor antagonism is that it leaves unaffected vascular ETB
      receptors, which mediate vasorelaxation, and non-vascular ETB receptors,
      particularly in the lung and kidneys, which act to clear ET from the plasma.
      PD156707 exhibits subnanomolar affinity and greater than 1000-fold selectivity
      for human ETA receptors and potently inhibits ET-1-mediated vasoconstriction in
      human isolated blood vessels. In rats, PD156707 has good oral bioavailability
      (41%) and a relatively short terminal t1/2 of approximately 1 h. Structural
      analogues of PD156707 that have comparable selectivity and potency for the ETA
      receptor are reported to have even better oral bioavailability and longer plasma
      t1/2 values. Preclinical studies with PD156707 indicate efficacy in animal models
      of congestive heart failure (CHF), pulmonary hypertension (PH) and cerebral
      ischaemia. We await data from clinical trials to confirm the therapeutic
      potential of the ETA-selective butenolide antagonists in man.

PMID- 15992062
TI  - Protein biotechnology: a BioUpdate Foundation post-experience course.

PMID- 15992061
TI  - The endopeptidase inhibitor, candoxatril, and its therapeutic potential in the
      treatment of chronic cardiac failure in man.
AB  - Candoxatril (UK-79300) is the orally-active prodrug of candoxatrilat (UK-73967),
      the active enantiomer of (+/-)candoxatrilat (UK-69578), a potent neutral
      endopeptidase (NEP) inhibitor. This article describes the rationale behind the
      use of such a drug in the treatment of chronic heart failure in man. It further
      describes the pharmacokinetics and pharmacodynamics of candoxatril in normal
      healthy individuals and in patients with chronic cardiac failure. In addition, we
      describe the initial results comparing candoxatril with furosemide and captopril
      in human heart failure.

PMID- 15992064
TI  - Biology of Nitric Oxide 6th International Meeting.

PMID- 15992063
TI  - 39th Interscience Conference on Antimicrobial Agents and Chemotherapy of the
      American Society for Microbiology.
AB  - The 39th ASM ICAAC Meeting, attended by over 16,000 delegates, highlighted
      numerous late-stage development antibacterials. The presentation of over 600
      reports (posters, symposia and oral presentations) regarding resistance emergence
      underscores the evolving landscape of antibiotic susceptibility worldwide.
      Although bacterial genomic efforts are slowly expanding the potential sources of
      novel targets, the established antibacterial classes, including quinolones, beta
      lactams, protein synthesis inhibitors and carbapenems, were most prevalent among
      the presentations. Quinolones dominated this conference, with many presentations
      of moxifloxacin (> 72 presentations), gatifloxacin (> 66 presentations) and
      gemifloxacin (> 59 presentations). The new class of antibacterials, the
      oxazolidinones, represented by Linezolid, was also highlighted.

PMID- 15992065
TI  - Vaccine strategies for infectious diseases.
AB  - Infectious diseases are the major cause of death worldwide; in developing
      countries such diseases are responsible for nearly half the burden of premature
      death and disability. Therefore, the need for the development of new vaccine
      strategies aimed at preventing or limiting disease is extremely urgent. Important
      successes have been achieved against some infectious diseases that were once
      endemic or, even, epidemic (e.g., polio, smallpox, diptheria). Advances in our
      knowledge of the pathogenesis and immune correlates of protections are needed to
      develop novel vaccinal approaches to diseases such as hepatitis C, AIDS and
      malaria. In this review we will analyse the biological problems associated with
      the prevention of development and/or improvement of vaccine strategies for
      infectious diseases, focusing on the difficulties facing the creation of new
      effective vaccines for HIV infection and malaria.

PMID- 15992066
TI  - Campylobacter vaccine development:a key to controlling enteric diseases.
AB  - Worldwide, Campylobacter jejuni is a major cause of diarrhoea and dysentery, with
      approximately 400 million cases occurring annually. Control of the disease
      through public health and antibiotic measures is insufficient, and vaccination
      offers the most promising solution. Infection produces immunity from disease,
      suggesting that vaccination may produce similar protection. Epidemiological data
      suggest that there are conserved antigens among serotypes; immunity against which
      protects against disease. Therefore a monovalent serotype vaccine seems
      practical. Several antigens on Campylobacter have been found to be immunogenic
      and, in some cases, associated with virulence. However, none of these proteins
      have been produced recombinantly in the proper conformation, nor have they been
      protective in preclinical models. For this reason, live attenuated or inactivated
      Campylobacter whole cell (CWC) vaccines may be the best approach. Development of
      an attenuated strain of Campylobacter has been complicated by the fact that the
      organism is highly transformable. Rec A mutants of Campylobacter have recently
      been constructed in an attempt to avoid this trait. Such mutants have been made
      defective in various virulence properties and are being evaluated for safety in
      preclinical models. Antex Biologics has made an inactivated CWC vaccine using the
      Company's patented NST (nutriment signal transduction) technology, whereby the
      cells are grown using physiologically logical conditions to maximise the
      expression of antigens associated with in vivo virulence. This vaccine has been
      shown to be safe, immunogenic, and protective in preclinical models of infection.
      Inclusion of a mucosal adjuvant in the vaccine increases the immunological
      response to the antigen. Recent Phase I and Phase II clinical trials, using the
      CWC vaccine formulated with an adjuvant and orally administered, show that the
      vaccine is safe and immunogenic in human volunteers. The approach used to develop
      this inactivated whole cell Campylobacter vaccine is also applicable for the
      rapid development of new vaccines against a variety of mucosal pathogens.

PMID- 15992067
TI  - Rabies DNA vaccines for protection and therapeutic treatment.
AB  - Rabies is a successful zoonotic disease that has persisted over time, achieving
      worldwide distribution in a variety of species. Annually, in developing countries
      with limited access to high-quality antirabies biologics, approximately 50,000
      individuals and millions of animals die of rabies. Many of these countries
      continue to use vaccines produced in sheep, goat or suckling mouse brain, with
      ultraviolet light or phenol inactivation of the virus. Although there are several
      efficacious rabies vaccines derived from cultured cells, such as the human
      diploid cell vaccine, they are costly to produce and prohibitively expensive for
      developing countries. DNA vaccines offer a new and powerful approach for the
      generation of needed vaccines. They are stable, inexpensive to produce, easy to
      construct and induce a full spectrum of long-lasting humoral and cellular immune
      responses. This review concerns the present state of rabies DNA vaccines, and
      addresses the technology that may enhance their therapeutic efficacy.

PMID- 15992068
TI  - In vitro activities of quinolones.

PMID- 15992069
TI  - Protein tyrosine phosphatases: their role in insulin action and potential as drug
      targets.
AB  - Protein tyrosine phosphatases (PTPases) are the enzymes responsible for the
      selective dephosphorylation of tyrosine residues. PTPases function to regulate a
      wide array of biological responses mediated by growth factors and other stimuli
      by balancing the cellular level of phosphotyrosine in concert with their
      counterparts, protein tyrosine kinases. The important roles which PTPases play in
      regulating intracellular signalling and, ultimately, biological function along
      with the recent availability of information regarding their structural features
      has highlighted them as potential targets for pharmacological modulation. This is
      demonstrated by the increased level of activity directed towards the
      identification of novel small-molecule PTPase inhibitors. The rationale and
      potential utility of this drug discovery approach is discussed here, with
      particular emphasis on its application for the treatment of insulin resistance
      and Type 2 diabetes.

PMID- 15992070
TI  - Targeting enzymes to cancers--new developments.
AB  - Two methods of using tumour located enzymes have been described. These are
      antibody directed enzyme prodrug therapy (ADEPT) and macromolecule directed
      enzyme prodrug therapy (MDEPT), where the tumour located enzyme converts a non
      toxic prodrug into a cytotoxic drug at tumour sites. The alternative use of
      tumour located enzymes is to inactivate rescue agents that protect cells from
      antimetabolite action, and is described as 'Antimetabolite with inactivation of
      rescue agent at cancer sites' (AMIRACS). The leakiness of tumour blood vessels
      and poor lymphatic drainage allows enzymes to be targeted to many cancers by
      attachment to polymeric macromolecules (MDEPT), as well as to antibodies and
      antibody fragments (ADEPT). To avoid systemic toxicity, enzyme activity in blood
      and normal tissues must be very low before giving a prodrug or rescue agent.
      Antibodies directed against the enzyme component of macromolecular conjugates
      have proved to be very efficient at clearing normal tissues. Human enzymes which
      are over expressed by cancer cells can be exploited particularly if they require
      co-factors or co-substrates, either in situ or targeted to extracellular sites.
      Bacterial enzymes have advantages in specificity but require some form of
      immunological control in view of their immunogenicity. Prodrugs which generate
      drugs with very short half lives are desirable, and have been developed,
      including one which has a differential toxicity between prodrug and the active
      drug of 1000 to 10,000 fold. The range of antimetabolites available for AMIRACS
      was initially restricted to inhibitors of dihydrofolate reductase but has been
      greatly extended by the introduction of inhibitors of other enzymes. The
      limitations of these systems are discussed.

PMID- 15992071
TI  - S 18326: a thrombin inhibitor that shows potential for oral treatment of
      thromboembolic disorders.
AB  - Antivitamin K agents are currently the only orally available anticoagulant
      compounds. During the past two decades, important research has focused on the
      discovery of a direct, orally active thrombin inhibitor. In 1991, DuP 714, a boro
      arginine derivative, was shown to possess anticoagulant activity in different
      animal species after oral administration. S 18326, structurally related to DuP
      714, is a further potent thrombin inhibitor. Moreover, its improved selectivity
      profile, associated with potent anticoagulant and antithrombotic properties,
      favours potential development of this compound for venous, as well as arterial,
      thromboembolism.

PMID- 15992072
TI  - Moxifloxacin (Bay 12-8039): a new methoxy quinolone antibacterial.
AB  - Moxifloxacin (Bay 12-8039) is a new 8 methoxy quinolone antibacterial. The MIC90
      values are < or = 0.25 mg/l for Streptococcus pneumoniae (irrespective of
      penicillin susceptibility), Haemophilus influenzae (beta-lactamase positive or
      negative), Morexella catarrhalis, Bordetella pertussis, Legionella sp.,
      Mycoplasma pneumoniae, Clamydia pneumoniae, Mycobacterium tuberculosis,
      methicillin-sensitive Staphylococcus aureus, beta-haemolytic streptococci
      (macrolide-sensitive or -resistant), Listeria sp., most Enterobacteriaceae,
      Salmonella sp., Shigella sp., Neisseria gonorrhoeae, N. menigitidis, Pasteurella
      spp., Vibrio spp. and Yersinia enterocolitica. For Mycobacterium intracellularae,
      methicillin-resistant S. aureus (MRSA), ciprofloxacin-resistant S. aureus,
      Citrobacter freundii, Providencia sp., Serratia sp., P. aeruginosa and other non
      fermentive Gram-negative rods, MIC90s are in the range 0.5-4 mg/l. For anaerobic
      bacteria species, MIC90s are also in the range 0.25-4 mg/l. Moxifloxacin is
      bactericidal at concentrations 2- to 4-fold higher than the MIC and is rapidly
      bactericidal against most common pathogen groups at concentrations achieved in
      serum with a 400 mg dose that is between 0.5-4 mg/l. There is a post-antibiotic
      effect against Gram-positive and -negative bacteria. Resistant mutants are at
      present difficult to select in the laboratory but in general, moxifloxacin has
      poorer activity against strains resistant to ciprofloxacin compared to those
      which are susceptible. Animal and laboratory pharmacodynamic models indicate that
      the MIC and area under the serum concentration time curve predict outcome.
      Various animal models mainly of respiratory tract infection indicate equivalent
      or superior results compared to existing or other developmental agents. Human
      pharmacokinetics in healthy volunteers indicate linear pharmacokinetics over the
      dose range 50-800 mg/day. A single dose of 400 mg produces a maximum serum
      concentration of 2.5-4.5 mg/l, half-life of 11-15 h, AUC of 25-40 mg x h/l and
      volume of distribution of 2.5-3.5 L/kg. Protein binding is about 50% and two
      metabolites have been identified (M-1 and M-2). Bioavailability is > 85% and a
      minority of clearance is via the kidneys. No dose modification is required in
      renal impairment. Extra vascular penetration, where studied, is comparable to
      that of other quinolones. At present undergoing clinical trials, with a focus on
      respiratory tract infection, it is likely that moxifloxacin will provide
      effective therapy for pathogens with MICs of < or = 0.25-0.5 mg/l. The safety
      profile in a large number of human subjects is awaited.

PMID- 15992073
TI  - The therapeutic potential of plant-derived vaccines and antibodies.
AB  - The production of recombinant proteins in plants is reviewed with a particular
      focus on plant-derived vaccines and antibodies for human healthcare. Issues
      relating to foreign gene expression, such as protein yield, localisation and
      glycosylation are also considered. Emphasis is placed on reporting progress with
      preclinical and clinical evaluation of plant-derived vaccines and antibodies. An
      assessment is made of the likely future direction of research and development in
      this area.

PMID- 15992074
TI  - The HepatAssist bioartificial liver support system: clinical study and pig
      hepatocyte process.
AB  - Based on perfusion of patient plasma through a circuit incorporating a hollow
      fibre membrane cartridge containing porcine hepatocytes, a bioartificial support
      system, or HepatAssist System, has been developed. Thirty-nine patients with
      acute liver failure (ALF) were treated in a Phase I multicentre clinical study.
      Thirty-two patients were bridged to orthotopic liver transplantation and six
      patients recovered without requiring a graft. Patient survival rate at one month
      was 90%. On the basis of these results, a multicentre Phase II/III, randomised,
      controlled, parallel group study of the HepatAssist System, compared to standard
      care in ALF patients has been initiated.

PMID- 15992075
TI  - Antisense oligonucleotide therapeutics.

PMID- 15992076
TI  - The potential use of MMP inhibitors to treat CNS diseases.
AB  - The matrix metalloproteinases (MMPs) are considered to be the physiological
      mediators of extracellular matrix remodelling. MMPs are involved in a variety of
      functions and in the nervous system, these include angiogenesis and the extension
      of neuronal growth cones during development. However, it has become increasingly
      evident that the aberrant expression of MMPs in the nervous system contributes to
      diseases that include among others, multiple sclerosis, malignant gliomas,
      Alzheimer's disease and stroke. This review highlights the evidence that MMPs are
      involved in diseases of the nervous system, and provides information for the
      potential beneficial use of MMP inhibitors in NS disorders. However, the
      application of MMP inhibitors to treat CNS diseases must be balanced carefully
      against the beneficial roles normally played by MMPs in CNS physiology or
      recovery.

PMID- 15992077
TI  - The therapeutic potential of novel aromatase inhibitors in breast cancer.
AB  - For over 20 years, aromatase inhibitors have played a role in the treatment of
      breast cancer. However, until relatively recently, their utility has been limited
      by a lack of selectivity and significant toxicity. Several second and third
      generation aromatase inhibitors which are highly selective for the aromatase
      enzyme have reached clinical trials this decade. As a result of these initial
      studies, aromatase inhibitors are now established as second line agents in the
      treatment of postmenopausal women with advanced breast cancer. They are now under
      evaluation in several other settings, including adjuvant and neoadjuvant therapy,
      and as part of combination treatment in premenopausal women. This review focuses
      on recent and ongoing clinical trials and the effect these have had on the
      clinical use of aromatase inhibitors.

PMID- 15992078
TI  - Zadaxin (thymosin alpha1) for the treatment of viral hepatitis.
AB  - Zadaxin (thymosin alpha1; Talpha1) is a synthetic 28 amino acid peptide with
      multiple biological activities primarily directed towards immune response
      enhancement. Since the immune system plays a critical role in the control and
      elimination of viral hepatitis infection, immune active agents such as Talpha1
      are of potential therapeutic value. In clinical trials, Talpha1 has been shown to
      be effective in chronic hepatitis B, both asmonotherapy and in combination with
      interferon-alpha (IFN-alpha). In chronic hepatitis C it was effective in
      combination with IFN-alpha. Since Talpha1 has few side-effects and is effective
      in combination with IFN-alpha, future clinical trials should evaluate the
      potential of Talpha1 to enhance the activity of antivirals such as IFN-alpha,
      ribavirin and lamivudine as viral hepatitis therapy.

PMID- 15992079
TI  - New therapeutic strategies in the treatment of hepatitis B virus infection.
AB  - Principally, because of the association of the chronic carrier state with the
      development of cirrhotic liver disease and hepatocellular carcinoma, chronic
      hepatitis B infection is a public health problem of global significance. In the
      main, therapy for chronic hepatitis B is limited to the use of alpha interferon
      for a limited number of chronic hepatitis B virus (HBV) carriers who have chronic
      hepatitis with active viral replication. The development of antiviral nucleoside
      analogues for the herpes viruses and human immunodeficiency virus (HIV) has
      resulted in the identification of several compounds which also have activity
      against HBV. Unfortunately, these agents have not been associated with the
      clearance of hepatitis B infection, but rather only the suppression of active
      infection while the patient is receiving medication. In addition, the development
      of drug-resistance to these agents by the virus will most likely limit their long
      term efficacy. Gene therapy has recently been applied to HBV both in vitro and in
      vivo. This has included the use of antisense oligodeoxynucleotides and RNA,
      ribozymes, dominant negative mutants and therapeutic HBV vaccines. These newer
      therapeutic modalities may hold promise as effective treatments for chronic
      hepatitis B, but to date, have been limited by the problem of delivery to the
      target cell population or infected organ in vivo. Combination nucleoside analogue
      therapy may also provide an important treatment modality for chronic hepatitis B,
      although this will require further investigation.

PMID- 15992080
TI  - Insulin glargine: the first clinically useful extended-acting insulin in half a
      century?
AB  - Insulin glargine (HOE 901) appears to be the first clinically useful extended
      acting insulin preparation for 50 years. A combination of a di-arginine addition
      to the C-terminal of the insulin B-chain, and a glycine substitution in the A
      chain, produce an insulin which is soluble at acid pH, but precipitates in sc.
      tissue at neutral pH after injection. This new insulin analogue has slightly
      lower receptor binding affinity compared to human insulin, but equal potency in
      vivo. Prolonged receptor binding is not found, and IGF-1 binding is not
      significantly different from human insulin. Glucose clamp and sc. disappearance
      studies confirm that insulin glargine has a much slower onset of effect than NPH
      (Neutral Protamine Hagedorn) insulin, and a much more protracted profile of
      action. Variability of absorption is difficult to assess from published studies,
      but is not dissimilar to NPH insulin. Patient studies in Type 1 and Type 2
      diabetes published to date are inconclusive, but appear to confirm differences in
      pharmacokinetics between insulin glargine and NPH, with significantly lower
      fasting plasma glucose levels or reduction in night hypoglycaemia. No safety
      concerns have emerged. It thus appears that insulin glargine is a genuinely new
      addition to the insulin family, and with further clinical experience it may well
      be possible to achieve better basal blood glucose control (without enhanced risk
      of hypoglycaemia), particularly at night or in conjunction with rapid-acting
      insulin analogues.

PMID- 15992081
TI  - Pharmacologic profile of certoparin.
AB  - The low molecular weight heparins (LMWHs) are now not only used for the
      prophylaxis and treatment of deep vein thrombosis (DVT), but also for the
      management of acute coronary syndromes. Beside these approved usages, the LMWHs
      have been developed for indications such as thrombotic and ischaemic stroke,
      cancer-associated thrombotic and vascular disorders, Alzheimer's disease and a
      variety of inflammatory disorders. In the United States, there are three approved
      LMWHs (enoxaparin, dalteparin and ardeparin). In Canada, reviparin and tinzaparin
      are also approved. The European Union has taken the lead; eight LMWHs are
      approved for various indications. Certoparin represents one of the earlier LMWHs
      used for DVT prophylaxis and treatment, with additional indications currently
      under development. Certoparin represents an isoamyl nitrite depolymerised LMWH
      with comparable structural characteristics to other nitrous acid depolymerised
      products such as nadroparin and reviparin. While comparable in structure to
      dalteparin, this agent differs in function due to a secondary purification
      process that is employed in the manufacture of dalteparin. The preclinical
      pharmacology of this drug has been extensively investigated. Although indication
      specific dosing and the optimisation of use in, for example, acute coronary
      syndromes and thrombotic stroke, may be require, certoparin represents a typical
      LMWH with comparable performance characteristics to some other agents. This
      chapter describes some of the preclinical and clinical pharmacologic
      characteristics of this drug. This information will be useful in designing
      clinical trials for newer indications of this drug.

PMID- 15992082
TI  - Pharmacology and clinical trial results of saruplase (scuPA) in acute myocardial
      infarction.
AB  - Saruplase is the non-glycosylated form of single chain urokinase-type plasminogen
      activator; it is produced by recombinant technique in Escherichia coli. Saruplase
      has plasminogen activating properties; it can also be cleaved to the potent
      plasminogen activator, double chain urokinase, resulting in the generation of
      plasmin. By means of a positive feedback mechanism, plasmin itself is able to
      cleave saruplase. At present, a bolus of 20 mg followed by an infusion of 60 mg
      over 1 h and preceded by a heparin bolus of 5000 U, represents the standard
      saruplase regimen. The PRIMI trial showed that this standard saruplase regimen
      achieves higher early patency rates than streptokinase. In the COMPASS trial,
      saruplase has been shown to be at least as effective as streptokinase, in terms
      of 30 day mortality. A comparative trial with urokinase (SUTAMI) resulted in
      similar late coronary patency. Saruplase has been tested against alteplase (100
      mg over 180 min) in the SESAM trial. The early coronary patency and safety of
      both regimens were comparable. In a recent study, three bolus applications of
      saruplase have been investigated. A double bolus of 40 mg each given 30 min
      apart, is suggested to be more effective than standard saruplase, but concerns
      about safety remain. Further studies are required to assess safety of the double
      bolus regimen, and to compare saruplase with the gold-standard of frontloaded
      alteplase, or the equivalent double bolus reteplase regimen.

PMID- 15992083
TI  - Therapeutic developments in amyotrophic lateral sclerosis.
AB  - There is currently no effective treatment for amyotrophic lateral sclerosis
      (ALS), a devastating disorder of the human nervous system that, due to
      motoneurone degeneration, causes progressive loss of muscle function and death.
      The relentless progression of ALS and the uniformly poor prognosis have been
      unhindered by a variety of therapeutic agents tested in previous clinical
      studies. Recently, two drugs, namely riluzole and recombinant human insulin-like
      growth factor-I (IGF-1), have been reported to benefit patients with ALS by
      improving survival or slowing disease progression. Several other drugs, such as
      gabapentin and various neurotrophic factors, are being investigated in on-going
      clinical trials. Therapeutic developments in ALS have been hampered by the fact
      that the precise cause of the disease remains unknown. In addition, there are
      considerable variations in disease related characteristics among patients,
      rendering accurate measurements of disease progression difficult. Advances in
      theories of pathogenesis, such as genetic factors, glutamate excitotoxicity,
      oxidative stress, autoimmune mechanism and cytoskeletal abnormality will help
      guide the development of future therapies. Newer approaches to therapy may
      include suitable glutamate antagonists, small molecules that augment neurotrophic
      factor function, and anti-oxidants. Combination therapy of effective agents
      should be considered.

PMID- 15992084
TI  - The therapeutic potential of CXC chemokine blockade in acute inflammation in the
      brain.
AB  - Mammalian neurones of the central nervous system (CNS) are terminally
      differentiated, and there is little endogenous capacity of the CNS to repair
      itself. Peripheral tissue injury, disease or infection results in a stereotypical
      inflammatory response to protect the host from pathogens and to promote tissue
      repair. However, collateral or 'bystander' damage is characteristic of any
      inflammatory response. Thus, it is apparent that the CNS has evolved mechanisms
      to regulate tightly the acute inflammatory response, and in particular to
      restrict the recruitment of neutrophils, in an attempt to protect itself from the
      potentially damaging consequences of inflammation in the brain. However,
      neutrophils are not always excluded from the brain. Indeed, they are found in
      large numbers in the brain parenchyma following traumatic lesions, stroke
      lesions, and in rodents, during the 'window of susceptibility'. Therapy targeted
      at blocking excitotoxic cell death has not successfully transferred from rodent
      models of stroke to human stroke patients. Restricting leukocyte entry to the
      brain, thereby inhibiting the inflammatory response, may prove to be a more
      practical therapeutic approach. The evidence presented in this review suggests
      that antagonising the effects of CXC chemokines may represent one route to
      achieve this goal.

PMID- 15992085
TI  - Dichloroacetate and cerebral ischaemia therapeutics.
AB  - Brain ischaemia is a major medical problem which totally lacks meaningful
      therapeutic options. A drug that reduces morbidity and mortality associated with
      head injury and stroke would constitute a major medical breakthrough. Although
      many mechanistic approaches have been evaluated clinically for both stroke and
      head injury, none have yet to be proven successful. Dichloroacetate (DCA,
      Ceresine) is a small molecule that activates pyruvate dehydrogenase (PDH) and
      crosses the blood-brain barrier. PDH activation reduces neurotoxic lactic
      acidosis which always accompanies brain ischaemia. DCA shows substantial efficacy
      in a variety of models of stroke, pre-stroke, head or spinal cord injury. Agents
      that lower cerebral lactic acidosis have not yet been clinically evaluated in
      head injury and stroke, although DCA has been shown clinically to reduce ambient
      lactate concentrations in patients with such conditions. DCA has also been shown
      to be well-tolerated in these patients, and unlike many halogenated molecules, is
      not mutagenic. Since elevated brain lactate is correlated with poor outcome in
      both preclinical and clinical studies, an agent such as DCA may prove to reduce
      the brain injury associated with these disorders. Potential clinical applications
      of DCA include stroke, head injury, spinal cord injury, and chronic disorders
      such as congenital lactic acidosis (CLA) and mitochondrial lactic acidosis and
      stroke-like syndrome (MELAS).

PMID- 15992086
TI  - The therapeutic potential of small molecule TACE inhibitors.

PMID- 15992087
TI  - Animal models of psoriasis.
AB  - Psoriasis is a common and chronic skin disorder under active investigation around
      the world. Despite this, determination of its genetic basis, role of the immune
      system in the disease pathophysiology and development of effective therapy, have
      been hampered severely by the absence of any spontaneous psoriatic skin disease
      in animals. Furthermore, until recently, validated animal models designed to
      create psoriasis were unavailable to investigative skin biologists and clinical
      scientists. However, there is at least one animal model which has been
      established and validated; it uses human skin engrafted on to severe combined
      immunodeficient (SCID) mice. In addition, there are several other rodent models
      which do not involve transplantation technology that share some (but not all)
      features in common with psoriasis. This review will summarise these available
      animal models and critique their relevance with respect to illuminating the
      immunogenetic basis of psoriasis and their value in screening novel treatments in
      a preclinical setting.

PMID- 15992088
TI  - Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with
      androgenetic alopecia.
AB  - In men who are genetically predisposed to develop androgenetic alopecia (AGA;
      male pattern hair loss), endogenous androgens alter scalp hair follicles,
      resulting in production of vellus-like, miniaturised hair, rather than
      cosmetically significant terminal hair. This change leads to a progressive
      decline in visible scalp hair density, readily perceived by the patient as
      thinning and, eventually, baldness. Dihydrotestosterone (DHT), a metabolite of
      testosterone produced by the enzyme 5alpha-reductase, has been implicated as the
      specific androgen in the pathogenesis of AGA. Men genetically deficient in the
      Type 2 isoenzyme of 5alpha-reductase do not develop AGA. Moreover, Type 2 5alpha
      reductase has been detected in scalp hair follicles, and balding scalps contain
      increased Type 2 5alpha-reductase activity and DHT levels. Taken together, these
      findings provide a rationale for the use of Type 2 5alpha-reductase inhibitors in
      the treatment of men with AGA. Finasteride, a specific and potent inhibitor of
      human Type 2 5alpha-reductase, decreases the formation of DHT from testosterone.
      Originally developed for the treatment of men with benign prostatic hyperplasia
      (BPH) as a 5 mg tablet, finasteride was subsequently evaluated as a treatment for
      AGA. Clinical studies in balding men demonstrated that finasteride reduced scalp
      DHT levels and improved hair growth, confirming the role of DHT in the
      pathophysiology of AGA. Dose-ranging studies established the optimal dose of 1
      mg/day for the treatment of men with this disorder. Large, multicentre studies
      established the safety and efficacy of finasteride 1 mg, leading to marketing of
      Propecia (finasteride 1 mg) as a new treatment for men with AGA.

PMID- 15992089
TI  - Paroxetine: a review of its pharmacology, pharmacokinetics and utility in the
      treatment of a variety of psychiatric disorders.
AB  - Paroxetine is a selective serotonin re-uptake inhibitor (SSRI). In vitro studies
      show that it is able to produce a concentration-dependent competitive inhibition
      of serotonin uptake into brain synaptosomes. This effect can also be demonstrated
      following in vivo administration of the compound to animals. Paroxetine is almost
      completely absorbed following oral administration. However, the drug undergoes
      extensive first pass metabolism. As a result, less than 50% of a single dose of
      paroxetine reaches the general circulation. Paroxetine is primarily metabolised
      by the cytochrome P4502D6 isoenzyme. The compound has also been shown to inhibit
      the activity of this enzyme. As a result, plasma levels of compounds metabolised
      by the cytochrome P4502D6 isoenzyme can be increased in patients given
      paroxetine. Paroxetine has been extensively evaluated in clinical studies in
      depressed patients. The compound shows efficacy superior to placebo, and similar
      to that obtained with standard tricyclic or tetracyclic agents. Paroxetine also
      appears to be as efficacious as other SSRIs. The efficacy seen in short-term
      studies with paroxetine in the treatment of depression is maintained when the
      drug is given chronically. More recently, paroxetine has been shown to be
      efficacious in the treatment of panic disorder, obsessive-compulsive disorder,
      and social anxiety disorder. Nausea, headache and somnolence are the most common
      adverse events reported by patients given paroxetine. As with other selective
      serotonin re-uptake inhibitors, a significant percentage of men under therapy
      with paroxetine report abnormal ejaculation. Paroxetine is well-tolerated by
      elderly patients, and appears to be associated with few serious adverse events.

PMID- 15992090
TI  - Risperidone (Risperdal): clinical experience with a new antipsychosis drug.
AB  - Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for
      serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha-
      adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic
      effects. Early studies demonstrated risperidone to be an effective medication for
      psychotic symptoms, probably more so than the older neuroleptics for both
      positive and negative symptoms. At clinically effective doses, risperidone causes
      no more extrapyramidal side-effects (EPS) than placebo; at higher doses EPS
      frequency increases in a dose-dependent manner. Since it became available in
      1994, extensive experience with the drug supports favourable early impressions of
      efficacy and tolerability. Minimal sedation, relatively little weight gain and
      absence of anticholinergic manifestations contribute to the relative tolerability
      of risperidone as compared to older neuroleptics. However, risperidone is
      associated with hyperprolactinaemia which can result in amenorrhoea and sexual
      dysfunction. Compared to older neuroleptics, pharmacoeconomic studies have shown
      that use of risperidone is associated with reduced hospitalisation and direct
      cost savings. A recent study found equivalent efficacy between risperidone and
      clozapine for treatment-resistant patients. Two studies comparing risperidone and
      olanzapine have yielded positive but conflicting findings. The overall positive
      experience with risperidone has resulted in the drug being widely recommended as
      a first line treatment option for psychoses.

PMID- 15992091
TI  - Entacapone, a catechol-O-methyltransferase inhibitor for treating Parkinson's
      disease: review and current status.
AB  - Levodopa, a dopamine precursor administered with a decarboxylase inhibitor, is
      the principal therapy for treating the symptoms of Parkinson's disease.
      Unfortunately, after approximately 2-5 years, it frequently loses its beneficial
      effects as evidenced by motor fluctuations. Entacapone (Comtan) is a selective,
      reversible catechol-O-methyltransferase inhibitor that dose-dependently increases
      the peripheral bioavailability of levodopa and prolongs its duration of action.
      Early studies confirmed that treatment with entacapone resulted in increased
      striatal uptake of levodopa after iv. administration of [18F] levodopa.
      Preclinical studies confirmed decreased formation of COMT-dependent metabolites,
      including 3-O methyldopa and homovanillic acid. Clinical studies performed in
      patients with motor fluctuations have shown that entacapone prolonged the
      duration of motor response by an average of 1-1.3 h. Parkinsonian patients
      receiving therapeutic doses of dopamine agonists and selegiline also experienced
      an incremental improvement in 'on' time when entacapone was added to their drug
      regimen. At present, there are no published safety studies beyond six to twelve
      months in duration, or studies in nonfluctuating patients. Based on the clinical
      trial data available, entacapone is well-tolerated in the majority of patients.
      Dopaminergic-related adverse effects include dyskinesias, nausea and dizziness.
      Non-dopaminergic adverse effects include diarrhoea, abdominal discomfort and
      discoloration of urine. Diarrhoea is occasionally severe and may require
      discontinuation of therapy. Of 406 entacapone-treated subjects, there was one
      incidence of elevated liver transaminases, although this was attributed to an
      underlying disorder. In the US, Phase III trials have been completed and a New
      Drug Application (NDA) has been filed. In Europe, the drug received a favourable
      review and is currently available.

PMID- 15992092
TI  - Metrifonate (Trichlorfon): a review of the pharmacology, pharmacokinetics and
      clinical experience with a new acetylcholinesterase inhibitor for Alzheimer's
      disease.
AB  - Metrifonate is a cholinesterase inhibitor, effective in the treatment of both the
      cognitive and behavioural symptoms of Alzheimer's disease (AD). Previously used
      as an antihelminthic and insecticide, clinical experience with metrifonate in AD
      patients is large and growing. The parent compound is relatively inactive; it is
      metabolised non-enzymatically to 2,2-dimethyl dichlorovinyl phosphate (DDVP),
      which irreversibly inhibits the acetylcholinesterase enzyme. The elimination half
      life of DDVP is 2.1 h; cholinesterase inhibition by DDVP is stable and may
      persist for up to 55 days. Metrifonate can be administered once daily. In vitro
      and animal data regarding possible carcinogenesis of metrifonate and DDVP are
      conflicting; experience in the treatment of humans with schistosomiasis or AD
      support its safety. Animal studies demonstrate its efficacy in enhancing memory
      in animals with cholinergic deficits. Double-blind, placebo-controlled studies
      have shown the benefit of metrifonate compared to placebo in improving scores on
      the Clinical Global Impression of Change, Alzheimer's Disease Assessment Scale
      Cognitive Subscale and the Neuropsychiatric Inventory.

PMID- 15992093
TI  - Efavirenz: shifting the HAART paradigm in adult HIV-1 infection.
AB  - Efavirenz (DMP-266, Sustiva, Stocrin) is a member of the non-nucleoside class of
      HIV-1 reverse transcriptase inhibitors. It has demonstrated potent antiretroviral
      activity in treatment-naive patients in combination with two nucleoside analogues
      or with a protease inhibitor. In nucleoside analogue-experienced patients, best
      activity has been seen with two nucleosides plus a protease inhibitor. An open
      label comparison versus indinavir plus two nucleoside analogues in predominantly
      treatment-naive patients, demonstrated that the efavirenz-based triple therapy
      provides at least similar antiviral effects, and possibly stronger effects, over
      48 weeks. Furthermore, fewer patients discontinued efavirenz-based triple therapy
      than indinavir-based therapy because of adverse events. Side-effects associated
      with efavirenz include a maculopapular rash and central nervous system (CNS)
      disturbances (dizziness, vivid dreams, poor concentration, sleep disturbances)
      which generally occur, and resolve, within the first weeks of therapy. Efavirenz
      will be used as a combination agent with other antiretrovirals where therapy for
      HIV infection is indicated.

PMID- 15992094
TI  - Grepafloxacin: an overview of antibacterial activity, pharmacokinetics, clinical
      efficacy and safety.
AB  - The treatment of respiratory tract infection is the most common reason for
      antibiotic prescribing. However, therapeutic options are diminishing as
      antibiotic resistance to penicillins and macrolides in key respiratory pathogens
      is increasing. As resistance increases, there are parallel rises in the number of
      treatment failures and the total cost of infection management. New generation
      broad-spectrum fluoroquinolones, such as grepafloxacin, have recently been
      recommended as a first-line treatment option in guidelines for lower respiratory
      tract infection. Grepafloxacin is an oral fluoroquinolone, with a microbiological
      and clinical profile that is particularly suited to the treatment of community
      acquired respiratory infections. In vitro, it is rapidly bactericidal, and
      compared with earlier quinolones, its broad spectrum activity encompasses all
      important respiratory pathogens; Streptococcus pneumoniae, Haemophilus
      influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae
      and Legionella pneumophila, including strains which are resistant to penicillin,
      other beta-lactam antibiotics and macrolides. In addition, grepafloxacin achieves
      high lung concentrations, and its long half-life (up to 15 h) enables once daily
      dosing. Overall, grepafloxacin combines the positive properties of the beta
      lactam antibiotics against conventional Gram-positive and Gram-negative
      respiratory pathogens, with the activity of the macrolides against atypical
      pathogens. In patients with bacteriologically documented infections, clinical
      studies in community-acquired pneumonia have shown that treatment for 7-10 days
      once daily (o.d.) with approximately 600 mg is equivalent to that with either
      twice daily (b.i.d.) clarithromycin 250 mg, or three times daily (t.i.d.)
      cefaclor 500 mg, and superior to that with t.i.d. amoxycillin 500 mg. In these
      studies, grepafloxacin proved effective in the treatment of both typical and
      atypical pneumonia. In acute bacterial exacerbations of chronic bronchitis
      (ABECB), 7-10 days treatment with o.d. grepafloxacin 400 mg or 600 mg has been
      shown to be equivalent to that with either t.i.d. amoxycillin 500 mg, or b.i.d.
      ciprofloxacin 500 mg. In patients with a documented bacterial pathogen,
      microbiological success with both grepafloxacin dosage regimens was superior to
      amoxycillin 500 mg t.i.d. In addition, short course treatment of ABECB with 400
      mg of grepafloxacin given o.d. for five days has been shown to be as effective,
      clinically and microbiologically as a ten-day course of the same dose. The safety
      profile of grepafloxacin has been well-characterised from data from over 12,000
      patients treated in Phase II/III and post-marketing studies, and over 400,000
      patients treated worldwide in routine clinical practice. The most commonly
      reported adverse events are gastrointestinal, mainly nausea and unpleasant taste.
      The potential for photosensitivity and central nervous system effects is low, and
      there have been no reports of convulsions. No unique or unexpected.

PMID- 15992095
TI  - Small molecule antagonists of alpha4 integrins: novel drugs for asthma.
AB  - The alpha4 integrins, alpha4beta1 (VLA-4) and alpha4beta7, are heterodimeric cell
      surface proteins expressed on leukocytes involved in both cell-cell and cell
      matrix interactions. These two integrins are key regulators of physiologic and
      pathologic responses in inflammation and autoimmune disease. In particular, their
      central role in animal models of allergic lung disease has been well documented,
      and suggests a key role in human asthma. In addition, integrins are proven valid
      targets for small molecule drugs, following the development of both parenteral
      and orally active antagonists of platelet integrin alphaIIbbeta3, and more
      recently, integrin alphaVbeta3. Therefore, there is a significant drive to
      develop small molecule inhibitors of alpha4 integrins for autoimmune diseases in
      general, and asthma in particular. The biology of alpha4 integrins in asthma has
      been recently reviewed, as has early work on the chemistry of alpha4 integrin
      antagonists. Here we summarise the recent rapid advances in this arena,
      particularly in the chemistry of alpha4 integrin small molecule antagonists, with
      emphasis on asthma as a clinical target.

PMID- 15992096
TI  - Tachykinins and kinins in airway allergy.
AB  - Using models of airway diseases, our understanding of the role of tachykinins and
      kinins in airway pathophysiology has been greatly enhanced by the recent
      development of a large series of peptide, peptoid and non-peptide antagonists for
      tachykinin and kinin receptors. This article reviews the experimental findings of
      the contribution of kinins and tachykinins and their respective receptors, in
      models of airway inflammation in response to agents known to trigger or worsen
      asthma attacks, such as antigen and cold air. Some new antagonists, mostly of a
      non-peptide nature, exhibit excellent pharmacodynamic and pharmacokinetic
      profiles; a brief account of early clinical studies in which they have been used
      is also given.

PMID- 15992097
TI  - Tissue-engineered skin substitutes.
AB  - The development of tissue engineered skin substitutes has reached a mature stage;
      major remaining questions relate to areas of greatest potential utility. Research
      is mainly concerned with extending indications of existing products, including
      treatment of the full range of acute, chronic, surgical and cosmetic wounds, and
      in other applications such as soft tissue augmentation and gene delivery. Among
      the few advances in the composition of skin substitutes is the inclusion of
      endothelial cells to provide a pathway for vascularisation by the host system.

PMID- 15992098
TI  - Gastrointestinal effects of COX-2 inhibitors.
AB  - The developing popularity of non-steroidal anti-inflammatory drugs (NSAIDs) over
      the last 100 years has been paralleled by an increase in associated
      complications, particularly affecting the gastrointestinal (GI) tract [1]. Over
      this period, there have been several attempts to develop less toxic NSAIDs, most
      of which have been unsuccessful. Since the discovery that the enzyme
      cyclooxygenase (COX) exists as two isoforms, the largely constitutive COX-1 and
      the mainly inducible COX-2, much interest has centred on the development of drugs
      capable of selectively inhibiting COX-2. Early studies that investigated specific
      COX-2 inhibitors (with no effect on the COX-1 isoform over the whole range of
      concentrations achieved in clinical usage) are encouraging, as they demonstrate
      that these drugs have fewer effects on gastroduodenal mucosa than standard NSAIDs
      given at equivalent doses. Further clinical experience with these agents outside
      trial settings and additional studies to assess the role of COX-2 when induced in
      the GI tract are needed, before such agents can be safely recommended for
      widespread prescribing.

PMID- 15992099
TI  - Potential new therapies for the treatment of acute pancreatitis.
AB  - The treatment of acute pancreatitis has remained virtually unchanged for the past
      50 years, in large part due to a poor understanding of the initial intracellular
      events. Furthermore, there is a lack of knowledge regarding the mediator(s)
      responsible for the progression of the disease from local pancreatic inflammation
      to a systemic inflammatory disease, as well as the mediator(s) responsible for
      distant organ dysfunction and failure. With recent advances in the
      pathophysiology of pancreatitis, in particular the role of the inflammatory
      mediators interleukin-1 beta, tumour necrosis factor alpha and platelet
      activating factor, the potential for new effective therapies has been realised.
      At present, a number of inflammatory mediator antagonists are being tested in
      humans, with the hope that we may soon develop a specific treatment for a
      disease, which thus far, has none.

PMID- 15992100
TI  - Potential therapy paradigms for Marfan syndrome.
AB  - Marfan syndrome is the most common genetic disorder of the connective tissue with
      an estimated prevalence of 1:10,000. The disease is characterised by
      manifestations in the cardiovascular, skeletal and ocular systems. The most
      severe manifestations are those of the cardiovascular system: mitral valve
      prolapse and dilation of the aortic root, which may progress to aortic
      dissection, a common cause of mortality in patients. Marfan syndrome is a
      dominant genetic disorder caused by mutations in the gene coding for fibrillin-1,
      the FBN1 gene. Fibrillin, a 347 kDa glycoprotein, is found in most connective
      tissues and is a major component of the extracellular microfibrils. More than 100
      different FBN1 mutations have been identified in individuals with Marfan
      syndrome, the majority of which are unique missense point mutations. Evidence
      suggests a dominant-negative mechanism of pathogenesis for the disorder, that is,
      the presence of the mutant fibrillin molecule interferes with the function of the
      normal protein. Therapies for dominant disorders such as Marfan syndrome (MFS)
      are likely to require both suppression of the disease allele expression and
      maintenance of expression of its wild-type counterpart. Thus, dominant genetic
      disorders present a unique therapeutic challenge. One approach to developing a
      therapy would be to use catalytic nucleic acid molecules. Antisense catalytic
      RNAs, or ribozymes, have been widely used to down-regulate or repair targeted
      gene expression respectively through the cleavage or trans-splicing of messenger
      RNA. Similarly, antisense DNA molecules or DNAzymes have been shown to be capable
      of cleaving target RNA molecules in a highly specific manner. This review will
      discuss the potential of catalytic nucleic acid molecules as therapeutic agents
      for MFS.

PMID- 15992101
TI  - Lessons learned about the therapeutic potential of the natural human immune
      response to lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths; patients with this disease
      often develop antibodies to their own tumour antigens. TB94 is one such human
      antibody, and was obtained from the natural immune response from a patient with
      lung cancer. The data generated so far on TB94 suggest that this human antibody
      may have clinical applications in the diagnosis and treatment of lung cancer.
      Since humans make antibodies to tumour antigens, the intelligence of the human
      immune response can be exploited for the discovery of potential novel antigens.
      These novel antigens can then be developed for vaccine applications. Creating
      effective strategies to analyse systematically the natural human immune response
      to tumour antigens will open up new areas of immunotherapy for the control and
      eradication of disease.

PMID- 15992102
TI  - Therapeutic potential of dendritic-based vaccines.
AB  - Involving a delicate balance of cell types, the interaction between the immune
      system and disease or abnormality in the human body is complex. Moreover, the
      mere presence of antigen and immune cells is necessary, yet insufficient to
      elicit immune reactivity. In order to elicit an immune response, an antigen in
      some form must be processed and presented to the immune system. Arguably, the
      most efficient antigen-presenting cell, the dendritic cell (DC), is the centre of
      intense investigation. The elicitation or cessation of an immune response is not
      a simple matter. The body must be able either to up-regulate (e.g., in the case
      of infectious disease) or down-regulate (e.g., in the case of transplantation)
      immunity to antigens located anywhere in the body. This sentinel role is capably
      filled via the distribution of Langerhans cells in the epidermis of the skin, and
      the migration of DCs throughout the lymphatic and circulatory systems. DCs are
      potent, as well as efficient: small numbers of cells and low levels of antigen
      still induce clinically relevant immunity. Lastly, they are capable of tolerance
      induction to self components by helping to delete self-reactive thymocytes and
      generating anergy in committed T-cells. Since DCs both initiate and modulate
      immunity, they are a component of a vast array of vaccines. This review
      highlights some of the intriguing basic research involving the development of DC
      based therapeutics. Furthermore, whenever an area of study has progressed to
      human treatment, recent and on-going clinical trials are discussed.

PMID- 15992103
TI  - Selenium-based drug design: rationale and therapeutic potential.
AB  - The wide media coverage given recently to a study correlating higher selenium
      levels with a reduced risk of advanced prostate cancer is but the latest addition
      to a growing body of epidemiological findings which link dietary selenium
      deficiency to diseases as diverse as cancer, heart disease, arthritis and AIDS.
      Indeed, selenium has a long history of association with human health and disease.
      Moreover, direct evidence is now emerging for specific beneficial effects of
      dietary selenium supplementation. Thus, the pharmacology, biology and
      biochemistry of selenium metabolism have become subjects of intense current
      interest. At the molecular level, selenium (as selenocysteine) is an essential
      component of the active sites of the enzymes glutathione peroxidase,
      iodothyronine 5'-deiodinase and mammalian thioredoxin reductase, and is also
      present in several other mammalian selenoproteins. Both glutathione peroxidase
      and thioredoxin reductase catalyse reactions essential to the protection of
      cellular components against oxidative and free radical damage. As a consequence
      of the growing recognition of the important biological role of selenium, a number
      of novel pharmaceutical agents, either selenium-based or which target specific
      aspects of selenium metabolism, are under development. Among these are orally
      active selenium-based antihypertensive agents, anticancer, antiviral,
      immunosuppressive and antimicrobial agents, and organoselenium compounds which
      reduce oxidative tissue damage and oedema. It can be anticipated that as our
      understanding of the basic biology and biochemistry of selenium increases, future
      efforts will uncover even more sophisticated approaches for the rational
      development of new selenium-based pharmaceutical agents.

PMID- 15992104
TI  - Newer calcium channel antagonists and the treatment of hypertension.
AB  - Calcium channel antagonists have become popular medications for the management of
      hypertension. These agents belong to the diphenylalkylamine, benzothiazepine,
      dihydropyridine, or tetralol chemical classes. Although the medications share a
      common pharmacological mechanism in reducing peripheral vascular resistance,
      clinical differences between the sub-classes can be linked to structural
      profiles. This heterogeneity is manifested by differences in vascular
      selectivity, effects on cardiac conduction and adverse events. The lack of
      differentiation between calcium channel antagonists in clinical trials has
      contributed to uncertainty associated with their impact on morbidity and
      mortality. Data from more recent studies in specific patient populations
      underscores the importance of investigating these antihypertensives as individual
      agents. A proposed therapeutic classification system suggests that newer agents
      should share the slow onset and long-acting antihypertensive effect of
      amlodipine. Additionally, a favourable trough-to-peak ratio has been recommended
      as an objective measurement of efficacy. The newer drugs, barnidipine and
      lacidipine, have a therapeutic profile similar to amlodipine, but trough-to-peak
      ratios are not substantially greater than the recommended minimum of 0.50.
      Aranidipine, cilnidipine and efonidipine have unique pharmacological properties
      that distinguish them from traditional dihydropyridines. Although clinical
      significance is unconfirmed, these newer options may be beneficial for patients
      with co-morbid conditions that preclude use of older antagonists.

PMID- 15992105
TI  - Lercanidipine: a novel lipophilic dihydropyridine calcium antagonist with long
      duration of action and high vascular selectivity.
AB  - Lercanidipine is a new 1,4-dihydropyridine derivative with potent, long-lasting
      and vascular-selective calcium entry blocking activity. Animal models of
      hypertension have shown lercanidipine to be potent, with a slow rate of onset and
      long lasting action and to have minimal or no effects on cardiac contractility.
      There was no evidence of tolerance after repeated oral treatment, and no effects
      were found on the autonomic nervous, central nervous, gastrointestinal or
      respiratory systems at antihypertensive doses. In man, lercanidipine is well
      absorbed after oral administration, with peak plasma levels occurring
      approximately 1.5 - 3 h after dosing. The drug is subject to extensive hepatic
      first pass metabolism with an elimination half-life of 2 - 5 h. With a more
      sensitive method, a mean terminal elimination half-life of 8 - 10 h was defined.
      Despite this short plasma half-life the drug has a long duration of action, most
      likely due to the high lipophilicity of lercanidipine and its partitioning in to
      the lipid bilayer of cell membranes, followed by diffusion to the receptor
      binding site. The efficacy of lercanidipine has been established in extensive
      clinical trials with comparison to both placebo and standard well-established
      antihypertensive therapies. These trials confirmed the efficacy of lercanidipine
      and its long duration of action which renders it suitable for once daily
      administration. Tolerability was good in all studies: the adverse event profile
      was comparable to that of placebo at lower doses, with a low incidence of
      palpitations and ankle oedema. Lercanidipine is a recently introduced example of
      a lipophilic and vasoselective dihydropyridine calcium antagonist which is an
      effective antihypertensive drug with a slow onset and long duration of action; it
      is associated neither with reflex tachycardia nor cardio-depressant activity.

PMID- 15992106
TI  - Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in
      the treatment of heart failure.
AB  - This review outlines the chemical properties, pharmacology and clinical trials
      data which support the development of nesiritide (synthetic human B-type
      natriuretic peptide, or hBNP) as a therapeutic agent for patients with
      decompensated congestive heart failure. Nesiritide is a 32-amino acid peptide,
      structurally identical to endogenous hBNP. Clinical trials with single bolus,
      repeated boluses and sustained infusions of nesiritide have demonstrated prompt,
      significant and sustained reductions in pulmonary capillary wedge pressure and
      increases in cardiac output, consistent with a direct vasodilator effect.
      Nesiritide has a short half-life, approximately 18 min, which is not dependent
      upon renal function. It not associated with tachyphylaxis through 24 h of
      therapy. Nesiritide is not an inotrope, and its action is not dependent upon beta
      adrenergic receptors. The safety profile has been excellent; the major adverse
      effect is hypotension. The frequency of ventricular arrhythmia is not increased
      in patients treated with nesiritide. In our opinion, nesiritide has many
      attributes of an ideal first-line therapeutic agent for decompensated heart
      failure.

PMID- 15992107
TI  - Tolterodine: a new antimuscarinic agent for the treatment of the overactive
      bladder.
AB  - Bladder hyperactivity is a debilitating problem that affects many individuals. A
      plethora of therapeutic options have been investigated to combat this condition,
      antimuscarinic therapy being the most widely used. Nevertheless, this medication
      group has historically been of limited benefit, due to its side-effect profile.
      Tolterodine is a new muscarinic receptor antagonist that has been shown to be
      equally effective when compared to oxybutynin. However, the side-effect profile
      for tolterodine is much better than this commonly used anticholinergic. It has
      reduced affinity for the salivary glands in animal studies, and, in clinical
      trials, there has been a reduced incidence of dry mouth with this medication. In
      Phase III studies, tolterodine has been shown to decrease the number of
      micturitions per day, decrease the number of incontinence episodes per day and
      increase the mean volume voided per micturition. The maximal effect of this
      medication may not be seen for 6 - 8 weeks after initiation of the drug although
      the exact explanation for this finding has yet to be completely elucidated. The
      recommended dose is 2 mg b.i.d., which should be adjusted for those with liver
      failure or those on drugs that inhibit the cytochrome P450 isoenzyme known as
      CYP3A4. In summary, tolterodine is an effective well-tolerated antimuscarinic
      which should be considered as a first-line treatment due to its more favourable
      side-effect profile when than other available medications.

PMID- 15992108
TI  - The endothelin receptor antagonist TAK-044 in the treatment of reperfusion injury
      in organ transplantation.
AB  - Ischaemia and reperfusion are complex interrelated events that involve the
      vascular endothelium. The endothelium produces endothelin (ET), the most potent
      vasoconstrictor identified to date. During ischaemia, endothelial transcription
      of ET is increased, leading to strong and sustained vasoconstriction. Ischaemia
      and reperfusion are indispensable parts of solid organ transplantation. Various
      experimental data discussed in this review show an efficacy of the mixed ET(A/B)
      antagonist TAK-044 in the treatment of reperfusion injury. The overall safety and
      tolerability of TAK-044 in humans seems to be excellent. Large clinical
      randomised trials on the use of TAK-044 in the treatment of reperfusion injury in
      different clinical situations are missing, nevertheless, the future for ET
      antagonists is promising.

PMID- 15992109
TI  - Risedronate, a novel pyridinyl bisphosphonate for the treatment of osteoporosis
      and Paget's disease of bone.
AB  - Osteoporosis and Paget's disease of bone are the most common metabolic bone
      diseases. They cause considerable disability and pain, and reduce quality of
      life. The elderly are at greatest risk of osteoporotic fractures, and in an
      ageing world population, the burden of the disease is likely to increase.
      Bisphosphonates are known to be effective antiresorptive agents for the treatment
      of Paget's disease of bone, postmenopausal osteoporosis (PMO) and corticosteroid
      induced osteoporosis (CIO). However, some bisphosphonates have been associated
      with troublesome gastrointestinal side-effects. Risedronate is a novel pyridinyl
      bisphosphonate recently approved in the USA for the treatment of Paget's disease,
      and is under development for the treatment of PMO and CIO. Risedronate is
      effective and well-tolerated in the treatment of Paget's disease. It has the
      shortest treatment regimen of any oral bisphosphonate; a two month course of
      therapy results in sustained remission, as determined by biochemical indices. The
      results of recent clinical trials suggest that risedronate is also an effective,
      well-tolerated therapy for PMO and CIO. Risedronate represents an advance in the
      therapeutic options available for the treatment of Paget's disease, and is
      expected to be of further value for treatment of PMO and CIO when it receives
      approval for use in these conditions.

PMID- 15992110
TI  - Oxcarbazepine: current status and clinical applications.
AB  - Oxcarbazepine (OXC) was introduced in 1990 and is now registered in 54 countries
      worldwide as monotherapy, as add-on treatment for partial seizures, with or
      without secondarily generalised seizures, and primary generalised tonic-clonic
      seizures. OXC and its active metabolite, monohydroxy derivative (MHD), block
      voltage-dependent sodium channels and may effect potassium and calcium channels.
      In animal models of epilepsy, OXC and MHD have efficacy similar to that of CBZ.
      There is no evidence for clinically important teratogenicity, mutagenicity or
      carcinogenicity. OXC has no effect on serum concentrations of hepatically
      metabolised anti-epileptic drugs (AEDs) and no clinically important interactions
      with common non-AEDs, other than hormonal contraceptives. MHD has low protein
      binding and linear pharmacokinetics. Adverse effects (AEs) are usually related to
      the central nervous system. Approximately three-quarters of patients who
      experience adverse effects with CBZ improve when switched to OXC, without loss of
      seizure control. The incidence of rash appears to be less than that expected with
      CBZ. While hyponatraemia may occur more often with OXC than with CBZ, it is
      rarely symptomatic. OXC is an effective and safe drug for the treatment of
      partial-onset and primary generalised tonic-clonic seizures. Placebo- and low
      dose controlled double-blind monotherapy studies prove that OXC has
      anticonvulsant activity and that therapeutic dosages may be obtained with a 24 h
      titration in hospitalised patients, if necessary. Comparative double-blind trials
      show that OXC has similar efficacy to VPA, CBZ and PHT, but has advantages
      compared to those agents in terms of pharmacokinetics, side-effects and
      tolerability.

PMID- 15992111
TI  - Summary from the 152nd meeting of the American Psychiatric Association.
AB  - The 152nd meeting of the American Psychiatric Association was held between 15th
      and 20th May 1999 in Washington DC; over 15,000 clinicians and researchers were
      expected to attend. The majority of the data presented at the meeting focused on
      new clinical research results for recently marketed products. Results from late
      stage clinical trials on new chemical entities in development were also presented
      at the conference.

PMID- 15992112
TI  - 8th Annual International Conference on Obesity and Non-Insulin Dependent Diabetes
      Mellitus: novel drug developments.
AB  - The 8th Obesity & Non-Insulin Dependent Diabetes Mellitus and Novel Drug
      Developments Conference organised by International Business Communication, Inc.
      was held on 19th - 20th, April 1999 in London, followed by an one-day symposium
      on Novel Drug Developments for NIDDM & Insulin Resistance. More than 100
      delegates from both academic and industrial institutes attended the two meetings.
      The presentations provided insights into the understanding of mechanisms and
      developments of novel drugs for treatments of obesity and Type 2 diabetes. This
      review offers a general overview of the fields in appetite suppression,
      thermogenesis and insulin sensitisation. Discussions focused on several emerging
      therapeutic areas, including novel compound developments and target
      identification of receptors, proteins and viruses with the use of conventional
      methods and recently emerged technologies, such as bioinformatics and
      invertebrate modelling of human systems.

PMID- 15992113
TI  - Role of oxidatively modified low density lipoproteins and anti-oxidants in
      atherothrombosis.
AB  - Retrospective studies have demonstrated an association between coronary artery
      disease (CAD) and increased plasma levels of oxidised low density lipoproteins
      (LDL). A very recent prospective study in heart transplant patients has
      demonstrated that oxidised LDL is an independent risk factor for transplant CAD,
      thus further supporting the hypothesis that oxidised LDL is actively involved in
      the development of CAD. The increase of circulating oxidised LDL is most probably
      caused by back-diffusion from the atherosclerotic arterial wall in the blood,
      independent of plaque rupture. Indeed, plasma levels of oxidised LDL were very
      similar in patients with stable CAD and in patients with acute coronary
      syndromes. These were, however, associated with increased release of
      malondialdehyde (MDA)-modified LDL. Oxidised LDL may be generated by radical
      mediated or by lipoxygenase or phospholipase catalysed lipid oxidation, and by
      myeloperoxidase catalysed protein and lipid oxidation. Prostaglandin synthesis by
      endothelial cells under oxidative stress and platelet activation are associated
      with the release of aldehydes; these induce the oxidative modification of the
      apolipoprotein B-100 moiety of LDL in the absence of lipid peroxidation, and thus
      generate MDA-modified LDL. Efficient prevention of in vivo oxidation may involve
      efficient cholesterol lowering, improving the anti-oxidative status of LDL by
      increasing the anti-oxidant content and increasing the oleate content of LDL, and
      by shifting the LDL away from phenotype B (characterised by small dense LDL
      particles). Anti-oxidative and anti-inflammatory enzymes associated with HDL may
      inhibit the oxidation of LDL or reverse the atherothrombotic effects of LDL.

PMID- 15992114
TI  - Therapeutic potential of G-protein coupled receptor kinases in the heart.
AB  - The actions of G-protein coupled receptor kinases (GRKs) critically regulate beta
      adrenergic receptor (betaAR) signalling. In the cardiovascular system, the betaAR
      signalling pathway controls important responses of the heart such as the ability
      to contract (inotropy), the ability to contract faster (chronotropy) and the
      ability to relax (lusotropy). The observation that the betaAR kinase (betaARK1,
      also known as GRK2), the most abundant GRK in the heart, is increased in
      cardiovascular disease associated with impaired cardiac function, suggests that
      this molecule could have pathophysiological relevance in the setting of heart
      failure. Technological advances in the genetic engineering of mice have provided
      a powerful tool to study the physiological implications of altering GRK activity
      and expression in the heart. Recent studies have demonstrated that betaARK1 plays
      a key role in not only the regulation of myocardial signalling, but also in
      cardiac function and development. Importantly, targeting the activity of GRKs,
      and betaARK1 in particular, appears to represent a novel therapeutic strategy for
      the treatment of the failing heart. At present, gene therapy modalities are being
      tested which inhibit the activity of betaARK1 in the heart. This technology makes
      it possible to test directly whether betaARK1 inhibition in the setting of heart
      disease will improve the function of the compromised heart. Thus, these genetic
      approaches or the development of small molecule inhibitors of GRK activity, may
      lead to novel therapeutic approaches for cardiovascular disease.

PMID- 15992115
TI  - The therapeutic use of glycoprotein IIb/IIIa inhibitors in acute coronary
      syndromes.
AB  - Acute coronary syndrome (ACS) embraces the clinical diagnoses of unstable angina
      and non-Q-wave myocardial infarction (NON-Q-MI). Conventional treatment for these
      conditions with aspirin, heparin and other anti-anginal drugs has its
      limitations. Treatment of acute symptoms with lytic therapy has not been
      beneficial. A large proportion of patients in this high-risk group will
      eventually need revascularisation due to ongoing symptoms. Platelet aggregation
      plays a crucial role in the pathogenesis of ACS and ischaemic complications of
      coronary intervention. The glycoprotein (GP) IIb/IIIa receptor, which belongs to
      a family of surface receptors called integrins, is the final step in this
      pathway. This has led to the development and use of GP IIb/IIIa inhibitors as
      potential therapeutic agents. Inhibitors developed so far include abciximab, a
      chimeric monoclonal antibody, and more recently, novel synthetic intravenous and
      orally administered competitive integrin blocking agents. To date, abciximab,
      tirofiban and eptifibatide are commercially available for clinical use. Completed
      clinical trials have looked at these agents as a primary treatment and as an
      adjunct to intervention for ACS; they have shown improvement over existing
      treatments, with reductions in the incidence of death, myocardial infarction
      (MI), refractory ischaemia and need for urgent revascularisation. Risk of
      bleeding and thrombocytopenia is low, and appears to be dose related and
      associated with concomitant treatment with high dose heparin. Cost benefit has
      been proven.

PMID- 15992116
TI  - Synthetic inhibitors of coagulation factor Xa.
AB  - The antithrombotic efficacy of low molecular weight heparins suggest that
      specific inhibition of blood coagulation factor Xa (fXa) is an appropriate target
      for drug discovery. Clinical evidence also supports the effectiveness of
      warfarin, an orally bioavailable non-specific anticoagulant. The reported
      synthetic fXa inhibitors are directed towards the enzyme active site, and have
      been mostly non-inhibitory against closely related proteases, such as thrombin
      and activated protein C. Several groups have reported potent lead compounds with
      in vitro human fXa inhibitory activities (Ki and IC50) in the nanomolar range.
      Preclinical data on oral bioavailability, plasma half-life of clearance and
      activity in animal models of thrombosis have been reported for a select few. In
      the absence of human data, it is hard to speculate if any of the inhibitors
      discussed here possess the proper combination of potency and bioavailability, to
      be an ideal fXa inhibitor drug candidate. Since the ultimate goal is to produce a
      'better warfarin', reproducibility of anticoagulation with a wider ratio of
      antithrombotic to antihaemostatic doses will be necessary for this class of
      inhibitors.

PMID- 15992117
TI  - Imidazoline receptors: new targets for antihyperglycaemic drugs.
AB  - In both animal models of Type 2 diabetes and in man, it has been evident for many
      years that certain imidazoline drugs can stimulate insulin secretion and improve
      glycaemia. This suggests that they may be useful new reagents for use in the
      management of Type 2 diabetes. However, despite their promise, no imidazoline
      compound has yet come into clinical use as an effective therapeutic agent in
      diabetes. This should not be taken as evidence of a flaw in the basic hypothesis,
      but derives, in part, from continuing ignorance about the molecular
      characteristics of imidazoline binding proteins, and the precise structure
      activity relationships of their ligands. In this review, the mode of action of
      antihyperglycaemic imidazoline compounds is considered, and the possibility
      discussed that these agents may interact with a unique subtype of imidazoline
      binding site associated with ATP-sensitive potassium channels. The functional
      consequences of this interaction are summarised together with evidence that the
      binding site may actually lie within the channel complex. Additional data
      implicating the participation of alpha2-adrenoceptors in some actions of
      imidazolines are evaluated, and examples of relevant drugs having encouraging
      therapeutic profiles are highlighted. The possibility that some anti-diabetic
      imidazoline reagents may exert extra-pancreatic effects is also considered.
      Overall, the article aims to highlight important developments within the field
      but also draws attention to those areas where controversy remains.

PMID- 15992118
TI  - Toxicity of hepatotoxins: new insights into mechanisms and therapy.
AB  - Liver injury caused by hepatotoxins, such as carbon tetrachloride (CCl4),
      ethanol, and acetaminophen (APAP), is characterised by varying degrees of
      hepatocyte degeneration and cell death via either apoptosis or necrosis. The
      generation of reactive intermediate metabolites from the metabolism of
      hepatotoxins, and the occurrence of reactive oxygen species (ROS) during the
      inflammatory reaction account for a variety of pathophysiologic pathways leading
      to cell death, such as covalent binding, disordered cytosolic calcium
      homeostasis, glutathione (GSH) depletion, onset of mitochondrial permeability
      transition (MPT) and associated lipid peroxidation. The metabolism of
      hepatotoxins by cytochrome P-450 enzyme subtypes is a key step of the
      intoxication; therefore, enzyme inhibitors are shown to minimise the hepatotoxin
      associated liver damage. Understanding the function of transcription factors,
      such as nuclear factor kappaB (NF-kappaB) in acute liver injury, may provide some
      answers as to the molecular mechanisms of toxic insults. Moreover, substantial
      evidence exists that MPT is involved in ROS-associated hepatocellular injury and
      new findings offer a novel therapeutic approach to attenuate cell damage by
      blocking the onset of MPT. Thus, oxidant stress and lipid peroxidation are
      crucial elements leading to hepatotoxin-associated liver injury. In addition to
      specific treatment for a given hepatotoxin, the general strategy for prevention
      and treatment of the damage includes reducing the production of reactive
      metabolites of the hepatotoxins, using anti-oxidative agents, and selectively
      targeting therapeutics to Kupffer cells or hepatocytes for on-going processes,
      which play a role in mediating a second phase of the injury.

PMID- 15992119
TI  - Progress in xenotransplantation.
AB  - Organ transplantation is considered the most effective treatment for end-stage
      organ failure; currently it is limited by a severe worldwide shortage of human
      donor organs. This has led to investigation of the potential use of animals as
      organ donors. For a number of reasons, the pig represents the most likely organ
      donor candidate. Transplantation of a vascularised porcine organ into a human or
      non-human primate results in an immediate and dramatic rejection process, known
      as hyperacute rejection, which is mediated by the binding of pre-existing
      antibody to the porcine graft and the subsequent activation of host complement.
      Strategies aimed at preventing this initial rejection have been largely
      successful in experimental models. This has allowed attention to turn towards an
      understanding of the immunological barriers comprising the next phase of
      xenograft rejection, termed acute vascular rejection. This delayed rejection
      process appears to be a humoral event, and it is likely that the control of
      antibody synthesis will play a pivotal role in overcoming the current barrier to
      successful xenotransplantation.

PMID- 15992120
TI  - Pharmacology of argatroban.
AB  - Argatroban, a synthetic peptidomimetic antithrombin agent, is the first clinical
      anticoagulant solely to target thrombin. For some time, this drug has been used
      in Japan for the management of thromboembolic disorders. Recently, it has been
      approved in Japan for use in thrombotic and ischaemic stroke. Despite a large
      number of preclinical studies on the pharmacology of this agent, clinical trials
      in Europe and North America were only initiated in 1996. Argatroban produces
      anticoagulant effects comparable to therapeutic heparinisation at concentrations
      of approximately 1 microg/ml. At concentrations of 5-10 microg/ml, this agent
      produces adequate anticoagulation for inteventional cardiovascular procedures and
      prolongs the activated clotting time (ACT) to 400-600 s. The predictable
      anticoagulant effect of this agent is relatively short lasting, and may not
      warrant pharmacologic neutralisation in the majority of patients. However,
      patients with hepatic dysfunction may need some means of neutralisation. Unlike
      heparin, this drug produces its anticoagulant effects by direct inhibition of
      thrombin and thrombin-mediated processes. This agent is not influenced by
      endogenous factors such as platelet factor 4 and other proteins which bind
      heparin. Argatroban's use does not lead to the formation of antiplatelet
      antibodies. Thus, this drug is useful in the management of heparin induced
      thrombocytopenic (HIT) patients. Although argatroban was initially developed for
      the management of deep vein thrombosis (DVT), based on its pharmacologic
      properties, it can be developed for safer anticoagulation in such indications as
      acute coronary syndromes, as an adjunct to thrombolytics, thrombotic and
      ischaemic stroke and inflammatory diseases resulting in thrombotic complications.

PMID- 15992121
TI  - Pharmacology of irbesartan.
AB  - Despite the introduction of new antihypertensive agents such as angiotensin
      converting enzyme inhibitors and calcium channel antagonists, the blood pressure
      of fewer than 30% of hypertensive patients is controlled with current therapies;
      compliance and continuation with medication are poor. The renin-angiotensin
      system is important in the pathophysiology of hypertension, end-organ damage and
      congestive cardiac failure. Irbesartan is an angiotensin II receptor antagonist
      that provides dose-dependent, specific, insurmountable blockade of the AT1
      receptor both in vivo and in vitro. It is rapidly absorbed after oral
      administration, has a bioavailability of 60-80% with no food effect, does not
      require metabolism to a bioactive compound, and is excreted by both biliary and
      renal routes so that dosage adjustments are unnecessary in patients with renal or
      hepatic disease. Irbesartan produces dose-dependent blood pressure reductions,
      with 24 h activity confirmed by ambulatory blood pressure monitoring. Irbesartan
      is effective in the elderly and non-elderly, men and women and in cases of mild
      and severe hypertension. The recommended starting dosage is 150 mg once daily
      (o.d.), which can be increased to 300 mg. Its antihypertensive effect is
      accentuated by diuretic co-administration. In controlled clinical trials,
      irbesartan was at least as effective as atenolol, hydrochlorothiazide, amlodipine
      and enalapril. In a double-blind study, irbesartan 300 mg was more effective than
      losartan 100 mg, and in a dose-titration study, irbesartan 150-300 mg produced
      significantly greater blood pressure reductions than losartan 50-100 mg. In
      pooled data from nine placebo-controlled studies, adverse event and
      discontinuation rates for irbesartan were similar to those for placebo, and there
      was no relationship between dose and adverse effects. Preliminary clinical data
      suggest positive haemodynamic effects in heart failure and renoprotective effects
      in diabetic nephropathy.

PMID- 15992122
TI  - Rizatriptan: a new 5-HT1B/1D receptor agonist for the treatment of migraine.
AB  - Rizatriptan (MAXALT MK-0462) is a new 5-HT(1B/1D) receptor agonist for the acute
      treatment of migraine. The marketed 10 mg and 5 mg oral doses are rapidly and
      consistently effective in relieving headache pain with associated migraine
      symptoms, and in enabling patients to return to their normal activities of daily
      living. Rizatriptan 10 mg is more effective than rizatriptan 5 mg. Compared to
      oral sumatriptan, the established agent in this class, rizatriptan has a shorter
      Tmax and greater bioavailability. In comparative clinical trials, the probability
      of having pain relief sooner was higher for rizatriptan 10 mg than for
      sumatriptan 100 mg or 50 mg. Over the 2 h after dosing, rizatriptan 10 mg was
      also superior to sumatriptan 100 mg and 50 mg on a range of other outcome
      measures. Both doses of rizatriptan are well-tolerated. The most common side
      effects are dizziness, drowsiness, and asthenia/fatigue, which are short-lasting
      and of mild or moderate severity. In summary, rizatriptan is an effective and
      well-tolerated acute treatment for migraine, which may offer some advantages over
      oral sumatriptan.

PMID- 15992123
TI  - Naratriptan: a review.
AB  - Even though naratriptan and sumatriptan are both 5-HT1B/5-HT1D receptor agonists,
      the biological and pharmacokinetic profile of naratriptan differs significantly
      from that of sumatriptan. With a plasma half-life of 6 h, very high oral
      bioavailability of 63-74% and higher lipophilicity than sumatriptan, naratriptan
      exhibits a distinct clinical therapeutic profile. The similar tolerability to
      placebo, prolonged efficacy for 24 h or more and very low headache recurrence
      rate make naratriptan an attractive option in the treatment of acute migraine.

PMID- 15992125
TI  - SMI meeting: innovations in cardiovascular drugs. March 3-4, 1999, London, UK.

PMID- 15992124
TI  - Ropinirole in the treatment of Parkinson's disease.
AB  - In this review, the pharmacokinetics, safety and tolerability, and clinical
      efficacy of ropinirole (Requip), a non-ergoline dopamine agonist approved for use
      in the treatment of Parkinson's disease (PD) are examined. A summary of
      preclinical and clinical studies is presented. Ropinirole is safe and efficacious
      as monotherapy in the treatment of early PD and as an adjunct to levodopa in more
      advanced cases.

PMID- 15992126
TI  - Transgenic manufactured biopharmaceuticals: a new method of drug manufacturing.
AB  - The limit to product yield in biotechnology is reached at 500 - 800 mg/l
      fermentation broth. However, if large quantities of proteins are required for
      products which have to be marketed as quickly as possible, biotechnology remains
      the technology of choice. Challenging biotechnology, transgenic manufacturing
      processes use animals or plants with a productivity of up to 20 g/l. Whereas
      animal transgenic technology still risks potential contaminantion with prions,
      transgenic plants offer a rather safer manufacturing technology. Since
      glycosylation of the protein is specific to the production organism from the
      onset of product development, it must be decided whether the therapeutically
      active protein should be produced by mammalian cell culture, transgenic animal or
      transgenic plant. This, however, requires a decision on the manufacturing
      technology, prior to the knowledge of dose and potential market.

PMID- 15992127
TI  - The therapeutic potential of targeting drugs at transcription factors.
AB  - The pivotal role of gene transcription in a plethora of biological processes
      indicates that transcription represents a suitable target for potential
      therapeutic intervention. Ultimately, the pathophysiology of numerous human
      disease processes must be understood in terms of changes in gene expression
      within relevant body cell types. There is mounting evidence that genetic
      variation in transcription factors and/or their binding-site sequences, as well
      as environmentally induced malfunctioning of these proteins, contribute to common
      multifactorial disorders including cancer, diabetes, ischaemic heart disease and
      neural disorders. Even in 'non-inheritable' infectious diseases, alterations of
      host-cell transcriptional regulation play an important role in pathogenesis. The
      enormous progress in understanding the mechanisms of transcriptional control
      offers hope for the development of a new generation of drugs. Such compounds
      could be specifically designed to modulate either the synthesis of transcription
      factors, the regulation of their activity by small-molecule bioligands or
      phosphorylation events, their interactions with activator/repressor proteins or
      their binding to DNA. Given the remarkable specificity of this approach, it is
      anticipated that these agents will provide superior tools for the prevention and
      treatment of a diverse panel of clinical disorders in the not too distant future.

PMID- 15992128
TI  - The therapeutic potential of nicotine and nicotinic agonists for weight control.
AB  - Transdermal nicotine patches have been successfully introduced as a safe and
      powerful aid to smoking cessation; this has contributed to the rising interest in
      additional therapeutic applications for nicotine and synthetic nicotinic
      agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a
      variety of disorders, including Alzheimer's and Parkinson's diseases, depression,
      attention deficit disorder, Tourette's syndrome and ulcerative colitis. These
      interests are partially fuelled by the urgent need of the tobacco industry to
      find new niches for nicotine in a world bound eventually to retire from cigarette
      smoking. At the same time, there is an increased interest in developing drugs for
      fighting obesity, a growing affliction of industrialised nations. This review
      presents data on the potential of nicotine, and in particular synthetic nicotinic
      agonists, for controlling body weight. Nicotinic agonists may become relatively
      safe, effective and inexpensive alternatives for several optional drugs currently
      being developed for treating human obesity, including beta-3-adrenergic agonists,
      leptin and its agonists, and neuropeptide Y antagonists.

PMID- 15992129
TI  - Vaccines for human papillomavirus-associated anogenital disease and cervical
      cancer: practical and theoretical approaches.
AB  - The association of genital warts, cervical dysplasia and cervical cancer with
      certain human papillomavirus (HPV) types indicates that vaccine strategies that
      target the virus could be effective in controlling disease onset and progression.
      Three vaccine strategies are available. Firstly, a prophylactic approach of
      immunisation with HPV virus-like particles to elicit neutralising antibody would
      prevent infection. Secondly, vaccination targeting replicating virus in
      suprabasal cells of infected anogenital epithelium would be an effective therapy
      for infection and early dysplasias. Thirdly, immunotherapy directed to the
      oncoprotein products of the HPV E6 and E7 open reading frames would be effective
      in the control of cervical carcinoma. We examine how these strategies may be
      augmented by contemporary vaccine technologies, in particular through the use of
      live recombinant vaccine vectors, specific targeting of antigen processing
      pathways, dendritic cell and 'polytope' approaches, to produce 'designer'
      vaccines of maximum specificity and efficacy. How these approaches are being
      exploited by vaccine manufacturers and in clinical trials is discussed.

PMID- 15992130
TI  - The role of herpes simplex virus thymidine kinase in the treatment of solid
      tumours.
AB  - Suicide gene therapy is the approach whereby the genetic alteration of a cell
      renders it susceptible to an otherwise non-toxic prodrug. Suicide gene therapy
      for solid tumours has progressed rapidly since the concept was originally
      described: nearly all tumour types have been explored, with some, such as glioma,
      melanoma and colon cancer frequently used experimentally. The exciting aspect of
      suicide gene therapy is the bystander effect, the phenomenon whereby there is
      extended tumour death when only a small fraction is transfected with the suicide
      gene. This phenomenon implies that there is a reduced need to target specifically
      all tumour cells, as the effect mechanism itself carries out this function. The
      bystander effect mode of action has not yet been fully characterised, but the
      role of gap junctions and the immune system are implicated as the main
      instruments in its potentiation. This approach is also amenable to
      pharmacological intervention, which may help to optimise parameters prior to
      commencing suicide gene therapy. Clinical trails have already commenced using
      this form of treatment and results are eagerly awaited.

PMID- 15992131
TI  - Diagnosis and treatment of nephrotic syndrome.
AB  - Prompt diagnosis is essential in the planning of effective treatment for the
      underlying diseases responsible for nephrotic syndrome. In this review, the
      typical clinical and laboratory features that facilitate diagnosis of these
      disorders are discussed. The distinction between systemic diseases, involving the
      kidney, and primary glomerular diseases is emphasised. These clinical and
      pathological distinctions influence prognosis, and form the basis of therapy to
      treat the underlying disorders. Our discussion focuses on diagnosis and specific
      treatment of these diseases, as well as therapy of the clinical consequences of
      nephrotic syndrome per se.

PMID- 15992132
TI  - Advances in vaccine delivery: transcutaneous immunisation.
AB  - Needle-free delivery of vaccines has become a global priority. Transcutaneous
      immunisation (TCI), topical application of vaccine antigens to the skin, can
      elicit systemic antibody and T-cell responses, suggesting that this new technique
      may provide a means for vaccination without needles. TCI requires the use of an
      adjuvant such as cholera toxin added to a vaccine antigen, such as diphtheria
      toxoid, to induce antibodies to diphtheria toxoid. The adjuvant and antigen are
      thought to target Langerhans cells, potent antigen-presenting cells found in the
      superficial layers of the skin. TCI appears to be a highly practical technique
      for delivery of vaccines that provides unique access to the immune system.

PMID- 15992133
TI  - Valspodar: current status and perspectives.
AB  - Valspodar (Amdray, SDZ PSC 833) is derived from cyclosporin, but lacks the
      immunosuppressive and most of the collateral activities of cyclosporin A (CsA,
      Sandimmune, Neoral); it exhibits an enhanced capacity to chemosensitise tumour
      cells showing the classical type multiple drug-resistance (MDR) associated with
      MDR1 P-glycoprotein (Pgp) overexpression. This valspodar-mediated
      chemosensitisation of MDR tumour cells is reviewed with regard to its mechanism
      of inhibition on Pgp flippase function, and its potential inhibition of
      anticancer drug (ACD) metabolisation by CYP3A enzymes is discussed. Potent
      inhibition of the membranous and cytoplasmic detoxification mechanisms expressed
      by cells at the absorption and clearance borders in the body by valspodar results
      in the many pharmacokinetic interactions with other drugs that are substrates of
      either, or both, Pgp and CYP classes of detoxifying enzyme. In view of the
      present ability to restrict oral bioavailability of valspodar within a narrow
      range, and to adapt adequately the chemotherapeutic dosages to achieve their
      equivalent exposure in the presence or absence of valspodar, current clinical
      data on its efficacy and safety permit optimism for ongoing Phase III trials. The
      potential of valspodar to increase exposure or to modulate the biodistribution of
      other chemotherapeutics, such as HIV protease inhibitors to the brain, is further
      evoked, as this might become another application of the new drug. This evaluation
      of valspodar compared to CsA attempts to interpret its mechanisms of action,
      rather than to serve as a complete and comparative repertoire of all published
      preclinical and clinical data.

PMID- 15992134
TI  - Paclitaxel: a hope for advanced non-small cell lung cancer?
AB  - Recent studies have shown that paclitaxel (Taxol); Bristol-Myers Squibb Co.,
      Princeton, NJ) is an active agent in the treatment of advanced non-small cell
      lung cancer (NSCLC). Early trials in patients with advanced NSCLC utilised a 24 h
      infusion schedule and reported objective tumour responses in 21 - 24% of
      patients. Shorter infusion schedules have equivalent efficacy, and combined
      results from 14 separate trials of single agent paclitaxel in advanced NSCLC show
      an overall tumour response rate of 26%. Alternative schedules of paclitaxel from
      the traditional regimen every three weeks are under active investigation, but it
      is premature to assess whether these will yield improved efficacy for patients
      with advanced NSCLC. A single multicentre randomised trial of paclitaxel versus
      best supportive care in advanced NSCLC showed a significant survival advantage
      for the chemotherapy arm. Two large randomised Phase III trials have shown that
      paclitaxel and cisplatin is modestly more effective than cisplatin and
      podophyllotoxin combinations. The addition of cisplatin or carboplatin to
      paclitaxel results in higher response rates than for each of the drugs as single
      agents, but it is unclear whether the combinations yield superior survival or
      quality of life compared to single agent paclitaxel, or to other paclitaxel
      containing regimens.

PMID- 15992135
TI  - An update on bicalutamide in the treatment of prostate cancer.
AB  - In this update, bicalutamide (Casodex, Zeneca Pharmaceuticals) has been confirmed
      as an effective, well-tolerated and convenient non-steroidal anti-androgen for
      advanced prostate cancer. Preclinical and clinical studies have indicated its
      potential as monotherapy, with quality of life advantages compared with
      castration. A head-to-head comparison with flutamide, where both anti-androgens
      were used as part of combined androgen blockade, has suggested that the choice of
      components in this regimen can influence outcome, and has demonstrated that
      bicalutamide is better tolerated than flutamide. There is also preliminary
      evidence to support the potential use of bicalutamide in treatment of early-stage
      disease and tumours that are refractory to other non-steroidal anti-androgens.

PMID- 15992136
TI  - Levobupivacaine: a new safer long acting local anaesthetic agent.
AB  - The choice of local anaesthetic is influenced by several factors; it must provide
      effective anaesthesia and analgesia for the duration of the procedure and meet
      the expectations for post-operative pain management. Of primary concern is
      patient safety. Bupivacaine, currently the most widely used long acting local
      anaesthetic agent in both surgery and obstetrics, generally has a good safety
      record but its use has resulted in fatal cardiotoxicity, usually after accidental
      intravascular injection. Hence, for several years there has been a need for a
      long acting local anaesthetic, similar to bupivacaine, but with an improved
      cardiovascular safety profile. Levobupivacaine, the single enantiomer version of
      bupivacaine, offers a new long acting local anaesthetic, clinically equivalent in
      anaesthetic potency to bupivacaine, but with a reduced toxicity profile.
      Preclinical studies, from in vitro in single ion channels to whole large animal
      models, have unquestionably demonstrated that levobupivacaine is significantly
      less CNS toxic and cardiotoxic than bupivacaine. Cardiotoxicity is less easy to
      study in man, as the clinical signs are not usually seen until the CNS toxicity
      is marked, and well beyond that which is tolerable to volunteers or patients.
      Nevertheless, levobupivacaine has been shown to have less effect on myocardial
      contractility and QTc prolongation, early signs of cardiotoxicity, than
      bupivacaine in healthy subjects. In clinical use levobupivacaine has been shown
      to be equally efficacious as bupivacaine at comparable doses and concentrations,
      and has been found to produce similar anaesthetic characteristics (onset,
      duration and density of block). As levobupivacaine now becomes commercially
      available, the database available with which to make efficacy and safety
      comparisons with other local anaesthetics will increase, and the true value of
      this new long acting local anaesthetic should become even more apparent.

PMID- 15992137
TI  - Alprostadil for the treatment of erectile dysfunction.
AB  - Erectile dysfunction (ED) is a common medical condition affecting over 20 m men
      in the United States. Efficacious medical therapy for the treatment of erectile
      dysfunction has been available since the early 1980s and can be divided into
      local pharmacotherapy and systemic therapy. Alprostadil, a synthetic form of
      prostaglandin E1, is a useful local pharmacotherapeutic agent for the treatment
      ED. Alprostadil is presently available for administration as an intracavernosal
      injection or an intraurethral suppository. Local alprostadil therapy is effective
      at restoring the ability to participate in intercourse in up to 70% of men with
      ED. The principle side-effects of alprostadil are local, with few systemic
      reactions. The mechanism of alprostadil, its efficacy in clinical trials and side
      effects are examined to outline the utility of alprostadil for the treatment of
      ED.

PMID- 15992138
TI  - Ongoing trials in motor neurone disease.
AB  - Motor neurone disease (MND) is a group of progressive neurodegenerative disorders
      that cause disability from weakness and lead to death from respiratory failure.
      The pathophysiology of the several forms of MND is unknown, but recent advances
      have led to clinical trials of therapeutic agents based on an improved
      understanding of the pathologic processes. The design of clinical trials in MND
      is challenging, because an effective drug cannot restore strength, but rather
      slow the rate of progression. Measurement of progression poses difficulties, and
      an optimum end-point measure has not been determined. This article will include
      the clinical features of MND, present the leading hypotheses about causes as they
      relate to drug therapy, discuss factors to consider in selecting informative end
      point measures, and will review past and current drug trials.

PMID- 15992140
TI  - IBC's 6th International Symposium on Obesity and 3rd International Symposium on
      Insulin Resistance: March 22-25, 1999, Washington, DC.

PMID- 15992139
TI  - American Association for Cancer Research 1999: 10-14 April, Philadelphia,
      Pennsylvania.
AB  - No genuinely new targets or drugs were disclosed; instead, data about known
      therapeutic approaches and compounds were consolidated. The results of Phase I
      clinical trials were presented for the two farnesyl transferase inhibitors R
      115777 and L 778,123. These results will certainly contribute to the debate
      concerning the best way to use signal transduction inhibitors in clinic. It will
      take many years to appreciate fully the clinical potential of such compounds.
      Many preclinical presentations were given on the subject of new tyrosine protein
      kinases inhibitors for the treatment of angiogenesis, with the target kinases
      being the epidermal growth factor receptor (EGF-R) family, cyclin-dependent
      kinases (CDKs) and vascular endothelial growth factor receptor (VEGF-R).
      Inhibitors with convincing in vivo antitumour activity belong exclusively to
      three chemical series, quinazolines, indolinones and pyrido-pyrimidines. Among
      these series, the principal new compounds are ZD 1490, PD 183805, PD 166285, SU
      6668 and GW 5181. Several new topoisomerases inhibitors (camptothecin
      derivatives: BNP 1350, BN-80915; epipodophyllotoxin derivative: F-11782) and new
      anitmitotic agents (taxoid: IDN -5109; D-24851) were also discussed.

PMID- 15992141
TI  - Triple nucleoside analogue antiretroviral therapy: expanding the treatment
      approaches for management of HIV infection.
AB  - The expanding range of drug options for the management of persons with HIV
      infection and concerns about the long-term safety of some treatment approaches
      has precipitated the HIV treatment community to examine a wider range of
      treatment approaches. One new therapeutic approach is to consider using three
      nucleoside analogue reverse transcriptase inhibitors, particularly as initial
      therapy. Recent data comparing triple nucleoside analogue therapy with
      established 'standard of care' triple therapy regimens have demonstrated similar
      antiviral effects and tolerability for such regimens. Efficacy and tolerability
      of triple nucleoside therapy has been demonstrated up to 96 weeks of therapy.
      This approach has advantages over conventional two nucleoside plus either a
      protease inhibitor or non-nucleoside reverse transcriptase inhibitor in terms of
      drug interactions and maintenance of multiple class options. It creates regimens
      which are, for the most part, compact, twice daily and non-food dependent.
      Specifically, this approach has already become widely established for individuals
      for whom drug interactions exclude the use of protease or non-nucleoside
      antiretrovirals. Triple nucleoside analogue therapy is likely to represent an
      attractive option for both physicians and patients; its use in clinical practice
      is likely to further expand.

PMID- 15992142
TI  - Therapeutic potential of blocking HIV entry into cells: focus on membrane fusion
      inhibitors.
AB  - Despite a number of recent therapeutic advancements, there remains an urgent need
      to develop a new class of therapy for human immunodeficiency virus (HIV). This
      review summarises attempts at blocking HIV binding and entry into host cells, an
      approach that would provide theoretical advantages over the currently available
      drugs targeting enzymes (reverse transcriptase and protease), brought into play
      in the later stages of the viral life cycle. The multi-step process of HIV entry
      into cells, binding of the surface glycoprotein (gp120) to the CD4 receptor and
      one of the chemokine receptors, followed by the membrane fusion step mediated by
      the transmembrane glycoprotein (gp41), has recently been understood with greater
      clarity. The importance of the chemokine co-receptors, such as CCR5 and CXCR4,
      for HIV entry may help to explain the limitations of earlier approaches using
      recombinant soluble CD4 or polyanionic compounds to interfere non-specifically
      with HIV glycoprotein function. Conversely, previous investigations demonstrating
      the in vitro inhibitory potential of beta chemokines themselves, or small
      molecule chemokine receptor inhibitors, may now be understood in a new light.
      Promising laboratory investigations (particularly with the bicyclam compound,
      AMD3100) and extensive pharmaceutical experience with related chemical structures
      suggest great potential for targeting the chemokine nexus. Finally, the evolution
      of transmembrane peptide investigations from the laboratory to early clinical
      trials is described. Clinical trials of T-20, a peptide designed to inhibit gp-41
      mediated fusion, have provided 'proof of concept' that therapeutics targeting a
      viral entry event can result in safe and potent inhibition of viral replication.
      The author speculates on the future prospect of using novel therapeutic
      strategies aimed at the initial interactions between HIV and target cells, in the
      battle against AIDS.

PMID- 15992143
TI  - New research in macrolides and ketolides since 1997.
AB  - Macrolide and ketolide antibacterials remain a very dynamically active group. To
      overcome erythromycin A resistance within Gram-positive cocci and bacteria, novel
      compounds have been semi-synthesised, such as ketolides and C-4'' carbamate
      erythromycylamine derivatives. The continual efforts of those studying macrolides
      have led to molecular level investigations into the mechanism of action of these
      antibacterials. Among all novel derivatives, only telithromycin and AB-773 are
      currently under development. No real novel developments have been seen with the
      15- and 16-membered ring macrolides, however, research is also continuing in this
      area. This review is an update of our knowledge in the field of macrolides.

PMID- 15992144
TI  - Mechanism of action of the oxazolidinone antibacterial agents.
AB  - Oxazolidinones represent a new class of synthetic antibacterial agents active
      against multiply-resistant Gram-positive pathogens, including methicillin
      resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci and
      vancomycin-resistant enterococci. Eperezolid and linezolid are two novel
      analogues, which have respectively completed Phase I and Phase II clinical
      testing. The lack of cross-resistance between oxazolidinones and other
      antibiotics supports a novel mechanism of action. Oxazolidinones are protein
      synthesis inhibitors which target an early step involving the binding of N
      formylmethionyl-tRNA to the ribosome. Binding studies demonstrate that these
      agents interact with the 50S subunit, but not the 30S subunit of the ribosome.
      Crosslinking experiments provide evidence for an interaction with both the 16S
      rRNA of the small subunit and the 23S rRNA of the large subunit. Development of
      resistance in the laboratory is slow, resulting in two independently isolated
      point mutations at G2447U and G2576U of the 23S rRNA. This review discusses the
      results of published studies involving oxazolidinone mechanism of action.

PMID- 15992145
TI  - Prospects for antisense agents in the therapy of bacterial infections.
AB  - Antisense agents have received widespread interest as potential therapeutic
      agents for a number of diseases, including cancer, inflammatory conditions and
      viral infections. However, less emphasis has been placed on their potential
      application in the therapy of bacterial infections. This review considers the
      reported effects of backbone modified oligonucleotides (phosphorothioate and
      methyl phosphonate analogues) as well as peptide nucleic acids (PNAs) on gene
      expression and bacterial growth. In addition to suppressing bacterial growth by
      decreasing the expression of essential genes, it is also evident that antisense
      agents can be specifically targeted to genes that control expression of
      antibiotic resistance mechanisms, thereby potentially restoring an antibiotic
      sensitive phenotype to the cell. Despite observations from several studies that
      antisense agents can interfere with bacterial gene expression in a sequence
      specific manner, their uptake into bacteria is poor. At present this is a
      limiting factor in their potential application as therapeutic agents for
      bacterial infections.

PMID- 15992146
TI  - Nitric oxide scavengers as a therapeutic approach to nitric oxide mediated
      disease.
AB  - The essential role of nitric oxide (NO) in normal physiology and its involvement
      in the pathophysiology of a variety of diseases render the compound an attractive
      therapeutic target. NO donor drugs are used in the treatment of hypotension and
      angina where abnormalities in the L-arginine-nitric oxide pathway have been
      implicated. Overproduction of NO has been associated with a number of disease
      states including septic shock, inflammatory diseases, diabetes, ischaemia
      reperfusion injury, adult respiratory distress syndrome, neurodegenerative
      diseases and allograft rejection. NO is produced by a group of enzymes, the
      nitric oxide synthases. Selective inhibition of the inducible isoform is one
      approach to the treatment of diseases where there is an overproduction of NO; an
      alternative approach is to scavenge or remove excess NO. A number of NO scavenger
      molecules have demonstrated pharmacological activity in disease models,
      particularly models of septic shock. These include organic molecules such as PTIO
      (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), haemoglobin derivatives
      such as the pyridoxalated haemoglobin polyoxyethylene conjugate (PHP), low
      molecular weight iron compounds of diethylenetriaminepentaacetic acid and
      diethyldithiocarbamate and ruthenium polyaminocarboxylate complexes. The data
      suggest a potential role for NO scavengers in the treatment of NO mediated
      disease.

PMID- 15992147
TI  - Daptomycin: a novel agent for Gram-positive infections.
AB  - The alarming increase in the incidence of Gram-positive infections, including
      those caused by resistant bacteria, has sparked renewed interest in novel
      antibiotics. One such agent is daptomycin, a novel lipopeptide antibiotic with
      proven bactericidal activity in vitro against all clinically relevant Gram
      positive bacteria. These include resistant pathogens, such as vancomycin
      resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA),
      glycopeptide intermediately susceptible Staphylococcus aureus (GISA), coagulase
      negative staphylococci (CNS) and penicillin-resistant Streptococcus pneumoniae
      (PRSP), for which there are very few therapeutic alternatives. Daptomycin
      provides rapid, concentration-dependent killing and a relatively prolonged
      concentration-dependent post-antibiotic effect in vitro. Spontaneous acquisition
      of resistance to daptomycin occurs rarely. Daptomycin exhibits linear
      pharmacokinetics, minimal accumulation with once-daily dosing, and low plasma
      clearance and volume of distribution. Phase II clinical trials indicate that
      daptomycin at doses of 2 mg/kg q24 h and 3 mg/kg q12 h is efficacious against
      skin and soft tissue infections and bacteremia, respectively. In addition,
      results in endocarditis suggested potential efficacy with higher doses. On the
      basis of clinical trials to date, it appears that daptomycin has an excellent
      safety profile, with the incidence and nature of serious adverse events
      comparable to those observed with conventional therapy. Adverse events associated
      with other classes of antimicrobials (nephrotoxicity, local irritation,
      ototoxicity, hypersensitivity, and gastrointestinal effects) were uncommon with
      daptomycin. Minimal skeletal muscle toxicity was seen at only the highest dose
      tested (4 mg/kg q12 h), predicted by elevations in serum creatinine
      phosphokinase, and readily reversible upon discontinuation of treatment. There
      were no signs of toxicity in cardiac or smooth muscle. Phase II and III clinical
      trials are underway to evaluate daptomycin for the treatment of Gram-positive
      bacteremia and complicated skin and soft tissue infections, respectively.
      Daptomycin holds promise as a rapidly acting and highly effective antibiotic for
      Gram-positive infections.

PMID- 15992148
TI  - Tacrolimus in liver transplantation.
AB  - Tacrolimus has been in clinical use for ten years. It was launched in a hail of
      publicity following the successful treatment of cases with apparently
      irreversible rejection using conventional immunosuppressive therapies. Since that
      time, the overall experience with the drug has increased considerably. The
      purpose of this article is to review tacrolimus comprehensively, including
      evidence derived from major clinical trials, to enable the reader to become
      familiar with its clinical role, including a comparison with its main competitor,
      cyclosporin. Tacrolimus was discovered in 1984, it predominantly acts via
      inhibition of T-cell mediated immunity, and to a lesser extent B-cell humoral
      immunity. The agent was introduced into clinical medicine in 1989 and was soon
      shown to be a highly effective immunosuppressive agent, receiving approval in
      1994 by the Food and Drug Administration (FDA) for primary immunosuppression in
      adult and paediatric liver transplantation. Tacrolimus has proved to be a major
      development in transplantation. Whilst the available data have been hindered to
      some extent by deficiencies of trial design in the major studies, there is still
      more comparative clinical data available for tacrolimus than for any of its
      predecessors. The overall balance of risk benefit is considered by many to be
      tipped in favour of tacrolimus; it is likely that with more long-term follow-up
      results becoming available in liver and other solid organ transplants, the
      benefits will appear clearer.

PMID- 15992149
TI  - AIT-082 as a potential neuroprotective and regenerative agent in stroke and
      central nervous system injury.
AB  - The synthetic purine 4-[[3-(1,6 dihydro-6-oxo-9-purin-9-yl)-1-oxypropyl] amino]
      benzoic acid (AIT-082, Neotrofin, leteprinim potassium) possesses several
      biological properties of note: it stimulates outgrowth of neurites from PC12
      cells and neurones, stimulates synthesis and/or release of neurotrophic factors
      from astrocytes, enhances nerve fibre regeneration in vivo and enhances of memory
      in animals and humans. AIT-082 also protects against glutamate neurotoxicity in
      vitro and in vivo, which has led to successful tests of AIT-082 in animal models
      of acute central nervous system injury. In such cases, AIT-082 probably functions
      by both acutely reducing glutamate excitotoxicity and, over a longer period, by
      enhancing neuronal sprouting and functional recovery.

PMID- 15992150
TI  - 99th general meeting of the American Society for Microbiology. May 30 - June 3
      1999, Chicago, Illinois, USA.

PMID- 15992151
TI  - The therapeutic potential of PDE4 inhibitors.
AB  - Phosphodiesterase enzymes are responsible for the inactivation of cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP).
      Phosphodiesterase 4 (PDE4) is a cAMP specific phosphodiesterase expressed in
      inflammatory cells such as eosinophils. Inhibition of PDE4 results in an
      elevation of cAMP in these cells, which in turn downregulates the inflammatory
      response. The anti-inflammatory effects of PDE4 inhibitors have been well
      documented both in vitro and in vivo in a variety of animal models. The potential
      use of PDE4 inhibitors as anti-inflammatory agents for the treatment of asthma
      and other inflammatory disorders has received considerable attention from the
      pharmaceutical industry, but to date, there are no selective PDE4 inhibitors on
      the market. Early PDE4 inhibitors, typified by rolipram, suffered from dose
      limiting side effects, including nausea and emesis, which severely restricted
      their therapeutic utility. Second generation compounds, including CDP840 and
      SB207499 (Ariflo), have been identified with reduced side effect liability.
      Recent evidence suggests a correlation between side effects and the ability of
      compounds to bind at the so-called high affinity rolipram binding site (HPDE),
      whilst beneficial effects appear to correlate with binding at the catalytic site.
      A number of companies are actively pursuing compounds which exhibit improved
      affinity for the catalytic site and reduced affinity for the HPDE, in the
      expectation that this will provide compounds with an improved therapeutic index.

PMID- 15992152
TI  - New developments in IL-6 dependent biology and therapy: where do we stand and
      what are the options?
AB  - Interleukin-6 (IL-6) is a four-helical protein which, on target cells, binds to a
      specific IL-6-receptor and two molecules of the promiscuous signal transducing
      protein gp130. Structure-function analysis defined three molecular contact sites
      between IL-6 and its receptor subunits. Using this information, competitive
      antagonistic proteins as well as hyperagonistic proteins were developed. Possible
      therapeutic applications of IL-6 antagonists are in IL-6 dependent haematological
      disorders (Castleman's disease, POEMS syndrome, multiple myeloma) and bone
      diseases (Paget's disease, osteoporosis). Designer IL-6 antagonists could
      suppress inflammatory activity in rheumatic and autoimmune diseases and could
      prevent secondary amyloidosis. IL-6 antagonists could also prove advantageous in
      myocardial infarction and unstable angina pectoris. IL-6 antagonists might slow
      down development of (mesangioproliferative) glomerulonephritis. On the other
      hand, hyperagonistic variants of IL-6 have a potential in ex vivo expansion of
      bone marrow stem cells and as thrombopoietic agents. They might also be developed
      into drugs to support liver regeneration in vivo and to treat stress-induced
      cardiac insufficiency.

PMID- 15992153
TI  - The multivalent minigene approach to vaccine development.
AB  - Epitope based minigenes (epigenes) have been under investigation for several
      years as an experimental approach to vaccination against infectious diseases. The
      essence of this technology is that short DNA sequences, encoding well-defined
      cytotoxic T-lymphocyte- (CTL), antibody- (Ab) or helper T-lymphocyte- (HTL)
      specific epitopes are used as immunogens. Compared to other vaccine strategies,
      several potential advantages are apparent. These include the increased 'safety'
      of an immunisation strategy that mimics antigen processing and presentation
      during natural infections, without actually causing disease, and the
      'flexibility' in epitope selection, which allows induction and optimisation of
      the desired type of immunity. In addition, the 'high immunogenicity' of epitope
      based constructs relative to constructs based on whole antigenic proteins is an
      important factor. This paper presents and discusses recent developments in the
      use of minigenes or multiple epitope genes that allow vaccines to be designed.
      The preclinical studies available to date clearly demonstrate the great potential
      of this vaccine approach, in terms of both prophylaxis and therapy.

PMID- 15992154
TI  - Death receptor-mediated suicide: a novel target of autoimmune disease treatment.
AB  - In the thymus, based on the reactivity of their T-cell receptor with self-MHC and
      antigenic peptides, developing immature T-cells undergo positive and negative
      selection. Cells recognising self-peptides and MHC with high affinity are
      considered autoreactive, and thus potentially harmful, and are eliminated by
      induction of apoptotic cell death. Thymic negative selection is, however, only
      incomplete and autoreactive T-cells escape into the periphery. It is not the
      presence of autoreactive mature T- and B-lymphocytes as the underlying cause of
      tissue destruction and development of autoimmune diseases, but their uncontrolled
      and excessive clonal expansion upon activation by self-antigen. Thus, potent
      regulatory mechanisms must keep these autoreactive cells under control to avoid
      their inappropriate activation. Recent evidence indicates that death receptors of
      the tumour necrosis factor receptor family play a central role in mediating
      antigen receptor-induced suicide of autoreactive T-lymphocytes. Defects in these
      apoptosis-inducing regulatory mechanisms may result in the development of
      autoimmune diseases. Therefore, enhancing the cell's own suicide program, offers
      a most attractive therapeutic target for the treatment of autoimmune diseases.

PMID- 15992155
TI  - Direct thrombin inhibitors: current status and future prospects.
AB  - Thrombin is a pivotal enzyme in the coagulation cascade and in the pathogenesis
      of thrombosis, which can lead to the occurrence of a number of coronary
      syndromes. Thrombin inhibition, by either recombinant or synthetic inhibitors,
      has now been recognised as a possible mechanism by which to modulate thrombosis;
      a cause of considerable mortality and morbidity, particularly in the western
      world. This approach represents a departure from established antithrombotic
      therapy, the mainstay therapies for which are aspirin, heparin or warfarin. There
      is now a body of clinical evidence with recombinant peptide or protein based
      thrombin inhibitors, and, to a lesser extent, synthetic agents, which give useful
      insights into the potential therapeutic impact of direct thrombin inhibitors. As
      well as defining the key clinical parameters where these drugs can be beneficial,
      clinical studies have also highlighted specific areas which need to be addressed
      by newer compounds in this class. A number of examples of low molecular weight
      and potentially orally available compounds are now in early clinical development;
      they may serve to answer many of the questions raised by Phase III trials with
      compounds based on hirudin.

PMID- 15992156
TI  - Development of selective aryl hydrocarbon receptor modulators for treatment of
      breast cancer.
AB  - The aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix DNA-binding
      protein that forms a transcriptionally-active heterodimer with the AhR nuclear
      translocator (Arnt) protein. The nuclear AhR complex is a ligand-induced
      transcription factor and the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) is a high affinity ligand for the AhR. TCDD induces a diverse
      spectrum of tissue-, sex- and species-specific biochemical and toxic responses in
      Ah-responsive cells/tissues including the inhibition of 17beta-oestradiol (E2)
      induced gene expression in the rodent uterus and mammary and in human breast
      cancer cell lines. TCDD also inhibits spontaneous and carcinogen-induced mammary
      tumour formation and growth in rodent models. Research in this laboratory has
      utilised the AhR as a target for developing anticancer drugs for treatment of
      breast cancer and two different structural classes of selective AhR modulators
      (SAhRMs) have been developed. Alternate-substituted (1,3,6,8- and 2,4,6,8-) alkyl
      polychlorinated dibenzofurans (PCDFs) and substituted diindolylmethanes (DIMs)
      bind the AhR and induce a pattern of AhR-oestrogen receptor (ER) inhibitory cross
      talk similar to that observed for TCDD including inhibition of mammary tumour
      growth at doses < 1.0 mg/kg/day. In contrast, effective doses of these compounds
      do not induce hepatic CYP1A1-dependent activity or other AhR-mediated toxic
      responses induced by TCDD. These results indicate that SAhRMs may be an important
      new class of drugs for clinical treatment of breast cancer via AhR-ER inhibitory
      cross-talk.

PMID- 15992157
TI  - Selective proteasome inhibitors as anti-inflammatory agents.
AB  - Nuclear factor kappaB (NF-kappaB) is an ubiquitous transcription factor and
      pleiotropic regulator of numerous inflammatory and immune responses. Once
      activated, NF-kappaB translocates from the cytosol to the nucleus of the cell,
      where it binds to its consensus sequence on the promoter-enhancer region of
      different genes. By so doing, this activates the transcription of a variety of
      different pro-inflammatory cytokines, adhesion molecules and specific enzymes,
      such as the inducible forms of nitric oxide synthase and cyclooxygenase. A number
      of different cytokines, bacterial products and oxidants activate NF-kappaB via
      selective phosphorlyation, polyubiquitination and degradation of the inhibitor
      protein, IkappaB. Since the 26S proteasome complex degrades the post
      translationally modified IkappaB, thereby liberating the transcriptionally active
      p50/p65 heterodimeric NF-kappaB, this proteolytic complex represents a critical
      step in the activation of NF-kappaB. This review discusses the basic biology of
      the ubiquitin-proteasome pathway as it relates to the inflammatory response, and
      highlights those studies demonstrating that selective proteasome inhibitors are
      effective anti-inflammatory agents in vivo.

PMID- 15992158
TI  - Treatment of Type 2 diabetes mellitus based on glucagon-like peptide-1.
AB  - Glucagon-like peptide-1 (GLP-1) is a peptide hormone released from the gut mucosa
      in response to meal ingestion. Its actions include stimulation of all steps of
      insulin gene expression, as well as beta-cell growth, inhibition of glucagon
      secretion, inhibition of hepatic glucose production, inhibition of
      gastrointestinal secretion and motility, and inhibition of appetite and food
      intake. Physiologically, therefore, GLP-1 is thought to act as an incretin
      hormone (intestinal hormones that enhance meal-related insulin secretion) and as
      one of the hormones of the ileal brake mechanism (endocrine inhibition of
      gastrointestinal motility and secretion in the presence of nutrients in the lower
      small intestine). However, because of these same actions, the hormone can
      normalise the blood glucose of patients with Type 2 diabetes mellitus, and, in
      contradistinction to insulin and sulphonylurea, it does not cause hypoglycaemia.
      Therefore, treatment of Type 2 diabetes based on GLP-1 is currently being
      investigated. As a peptide, it must be administered parenterally, and, in
      addition, it is metabolised extremely rapidly. However, several methods to
      circumvent these problems have already been developed. A GLP-1- based therapy of
      diabetes mellitus and perhaps also obesity is therefore likely to become a
      realistic alternative to current therapies of these disorders.

PMID- 15992159
TI  - ISIS 2302, an antisense inhibitor of intercellular adhesion molecule 1.
AB  - ISIS 2302 is a 20 base phosphorothioate oligodeoxynucleotide (ODN) that inhibits
      intercellular adhesion molecule 1 (ICAM-1) expression through an antisense
      mechanism. Murine and rat analogues have been effective at doses of 0.06 - 10
      mg/kg in a spectrum of models of human inflammatory diseases and allograft
      transplantation, and ISIS 2302 inhibits the upregulation of ICAM-1 expression in
      a variety of human cells in vitro. In animals, including primates, plasma
      distribution half-life ranges from 30 - 60 min, but tissue elimination half-lives
      range from 1 - 5 days, and the compound is metabolised as other nucleic acids. In
      a Phase I iv. study, the pharmacokinetic behaviour of ISIS 2302 was similar to
      that in other primates, and single and multiple every other day doses from 0.06 -
      2 mg/kg infused over 2 h were well-tolerated. Phase IIa studies have been
      completed in Crohn's disease, rheumatoid arthritis, and psoriasis, and a combined
      Phase I/II renal allograft acute rejection prophylaxis study has just completed
      enrolment. In these studies, ISIS 2302, 0.5 - 2 mg/kg, or placebo was
      administered iv. every 2 - 3 days over 14 - 26 days (7 - 13 infusions) to 17 - 52
      patients, with follow up for 6 months. In the Crohn's study, evidence of highly
      durable (5+ month) remission-inducing and steroid-sparing properties were
      demonstrated, without clinically important adverse events. A 300-patient, pivotal
      quality trial investigating the steroid-sparing and remission-inducing qualities
      of ISIS 2302 in patients with steroid-dependent Crohn's disease is completely
      enrolled, with results expected in the first half of 2000. Modest efficacy and
      excellent tolerability were demonstrated in the psoriasis and rheumatoid
      arthritis trials. A Phase IIa trial of a topical formulation in patients with
      psoriasis is expected to commence in late 1999, as is a trial of an enema
      formulation in distal ulcerative colitis. Administration by nebulisation for
      asthma is undergoing preclinical evaluation. Execution of future plans in organ
      transplantation will await the results of the ongoing Phase I/II trial.

PMID- 15992160
TI  - Insulin aspart: a novel rapid-acting human insulin analogue.
AB  - In order to improve therapy and increase the quality of life for diabetic
      patients, it has been of significant interest to develop rapid-acting insulin
      preparations that mimic the physiological meal-time profile of insulin more
      closely than soluble human insulin. Insulin aspart (B28Asp human insulin) is a
      novel rapid-acting insulin analogue that fulfils this criterion. The B28Asp
      modification weakens the self-association of the insulin molecule and provides a
      more rapid absorption from the sc. injection site. The preclinical evaluation in
      vitro and in vivo demonstrates that apart from the more rapid absorption, insulin
      aspart is equivalent to human insulin. Thus, insulin aspart is equivalent to
      human insulin on key in vitro parameters such as insulin receptor affinity,
      insulin receptor dissociation rate, insulin receptor tyrosine kinase activation,
      IGF-I receptor binding affinity, metabolic and mitogenic potency. In accordance
      with the equivalent in vitro profiles, the toxico-pharmacological properties of
      insulin aspart and human insulin are also identical. The available data for
      insulin aspart and other rapid-acting insulin analogues supports that in vitro
      assays are sensitive and valuable in the preclinical evaluation of insulin
      analogues. Clinical studies demonstrate that insulin aspart has a pharmacokinetic
      and pharmacodynamic profile superior to that of soluble human insulin. In Type 1
      diabetic patients on a basal-bolus injection regimen, insulin aspart given
      immediately before the meals provides an improved postprandial glycaemic control
      and an improved long-term metabolic control, as compared to soluble human insulin
      given 30 min before the meals, without increasing the risk of hypoglycaemia.
      Taken together, the data support the hope that insulin aspart will allow the
      diabetic patient to combine a more flexible lifestyle with better glycaemic
      control, without any increased safety risk.

PMID- 15992161
TI  - Clinical and pharmacological experience with etanercept.
AB  - Tumour necrosis factor (TNF) is the dominant mediator of the cytokine cascade
      that causes inflammation and joint destruction in rheumatoid arthritis (RA). A
      new class of agent under investigation, the biological TNF inhibitors, inhibit
      the activity of TNF. Recombinant human TNF receptor p75 Fc fusion protein
      (TNFR:Fc; etanercept) blocks the activity of the cytokine TNF. Etanercept
      (Enbrel) was recently approved by the Food and Drug Administration for the
      treatment of RA. Etanercept is a genetically engineered recombinant soluble TNF
      receptor fusion protein that binds to TNF body and inhibits its biologic action;
      it is the first biotechnology product approved for the treatment of RA.
      Remarkable progress has been achieved in the treatment of RA with the development
      of TNF antagonists. Recent clinical trials have improved our understanding of the
      major role played by the cytokine TNF in provoking joint inflammation in RA.

PMID- 15992162
TI  - Fibrinolytic and antithrombotic regimens in recently completed, ongoing and
      planned clinical trials in myocardial infarction.
AB  - Myocardial infarction carries significant short-term and long-term risks of
      morbidity and mortality. Traditional treatment for acute myocardial infarction
      has significantly improved the outcomes of patients suffering from this
      condition. Recent clinical trials have focused on the use of novel fibrinolytics,
      glycoprotein IIb/IIIa receptor antagonists, low-molecular-weight heparin, direct
      thrombin inhibitors and myocardial protection, in an attempt to improve the
      prognosis of these patients. This clinical trials report reviews the rationale
      and design of recently completed, ongoing and planned major Phase II and III
      clinical trials on fibrinolytic and antithrombotic regimens for the treatment of
      myocardial infarction.

PMID- 15992163
TI  - 26th FEBS meeting: news of new and old therapeutic targets. June 19-24, 1999,
      Nice, France.

PMID- 15992164
TI  - 59th annual meeting of the American Diabetes Association. June 19-22, 1999, San
      Diego, CA, USA.
AB  - This year's annual meeting of the American Diabetes Association was held in San
      Diego and, as in recent years, was attended by over 6000 people. The various
      presentations, which featured almost 1500 papers with additional symposia
      covering a broad range of topics, more than filed the three-and-a-half day
      schedule. The abstracts of the papers are published in Diabetes 48 (Suppl. 1).
      Expanding awareness of therapeutic need, growing knowledge in the understanding
      of the pathogenesis and underlying biology of diabetes and successful development
      and growing use of new therapeutics, are all contributing to the rapid growth
      seen in this area. This meeting highlight is brief review of some of the topics
      which were extensively covered at the meeting.

PMID- 15992165
TI  - The HIV-1 Nef protein as a target for antiretroviral therapy.
AB  - HIV-1 Nef is a peripheral membrane protein that affects both signal transduction
      and membrane trafficking in infected cells. Alterations in these cellular
      processes enhance the efficiency of viral replication and the pathogenesis of
      AIDS in vivo. The precise mechanisms by which Nef functions are not fully
      elucidated. Nef is not an enzyme but appears to act as a linker molecule,
      mediating a variety of protein-protein interactions. Structural, biochemical and
      mutational data have allowed tentative identification of the key interactive
      surfaces on Nef, their cellular partners and their roles in Nef activity. Nef
      contains an SH3-binding surface through which it can interact with cellular Src
      family tyrosine kinases and/or activator molecules for small GTPases involved in
      signal transduction. This SH3-binding surface is important for the ability of Nef
      to facilitate the activation of host T-lymphocytes, a process which renders the
      cells more permissive for viral replication. Nef also contains two relatively
      unstructured, solvent-exposed loops, through which it interacts with the cellular
      proteins that coat vesicles involved in membrane trafficking. These surfaces are
      important for Nef-mediated alterations in the subcellular distribution of
      transmembrane proteins, a process which causes diverse effects, including the
      assembly of maximally infectious viral particles and viral evasion of the host
      immune system. These data provide precise molecular targets within the Nef
      protein. Molecules that bind these interactive surfaces are predicted to inhibit
      Nef activity and provide the basis for novel chemotherapeutic agents for the
      treatment of HIV-infection.

PMID- 15992166
TI  - Peptide deformylase: a target for novel antibiotics?
AB  - Peptide deformylase (PDF) catalyses the hydrolytic removal of the N-terminal
      formyl group from nascent ribosome-synthesised polypeptides. Its activity is
      essential and it is present in all eubacteria. It is also present in the
      organelles of some eukaryotes. PDF represents a novel class of mononuclear iron
      protein, utilising an Fe(2+) ion to catalyse the hydrolysis of an amide bond. Due
      to its extreme lability, isolation and characterisation of PDF was not possible
      until very recently. This review will discuss the recent progress in the
      elucidation of the the structure and function of PDF, evaluating its suitability
      as a target for antibiotic design and summarising the current approaches to
      designing drugs that target PDF.

PMID- 15992167
TI  - Peptide deformylase as an emerging target for antiparasitic agents.
AB  - Peptide deformylases (PDFs) constitute a growing family of hydrolytic enzymes
      previously believed to be unique to Eubacteria. Recent data from our laboratory
      have demonstrated that PDF orthologues are present in many eukaryotes, including
      several parasites. In this report we aim to explain why PDF could be considered
      to be a potent target for human and veterinary antiparasitic treatments.

PMID- 15992168
TI  - Ion channels involved in stroke.
AB  - Ion channels are membrane proteins that flicker open and shut to regulate the
      flow of ions down their electrochemical gradient across the membrane and
      consequently regulate cellular excitability. Every living cell expresses ion
      channels, as they are critical life-sustaining proteins. Ion channels are
      generally either activated by voltage or by ligand interaction. For each group of
      ion channels the channels' molecular biology and biophysics will be introduced
      and the pharmacology of that group of channels will be reviewed. The in vitro and
      in vivo literature will be reviewed and, for ion channel groups in which clinical
      trials have been conducted, the efficacy and therapeutic potential of the
      neuroprotective compounds will be reviewed. A large part of this article will
      deal with glutamate receptors, focusing specifically on N-methyl-D-aspartate
      (NMDA) receptors. Although the outcome of clinical trials for NMDA receptor
      antagonists as therapeutics for acute stroke is disappointing, the culmination of
      these failed trials was preceded by a decade of efforts to develop these agents.
      Sodium and calcium channel antagonists will be reviewed and the newly emerging
      efforts to develop therapeutics targeting potassium channels will be discussed.
      The future development of stroke therapeutics targeting ion channels will be
      discussed in the context of the failures of the last decade in hopes that this
      decade will yield successful stroke therapeutics.

PMID- 15992169
TI  - ETS transcription factors and targets in tumour invasion, angiogenesis and bone
      metastasis.
AB  - The ETS gene family encodes unique transcription regulators that have a common
      ETS DNA binding domain. At least 25 distinct ETS related genes have been isolated
      from various species. The ETS family transcription factors are known to regulate
      genetic programs essential for differentiation and development processes and play
      diverse roles in a number of biological processes such as organogenesis and
      tissue remodelling during murine development, hematopoiesis, B-cell development,
      activation of T-cells and signal transduction, as well as osteogenesis,
      osteoblast differentiation and extracellular matrix mineralization. Based on the
      observation of overexpression of ETS related genes in various primary and
      metastatic tumors, their utility as potential therapeutic targets has been
      suggested. Antisense oligonucleotides, transdominant, and dominant-negative
      mutants have been exploited to target and inhibit ETS gene expression
      selectively. These ETS-targeted studies are being pursued to assess their
      antitumour effect, and hold the potential that such specific ETS-targeted
      inhibitors may become a viable option for cancer therapy. Collectively, these
      studies also demonstrate that Ets factors can regulate multiple aspects of the
      malignant phenotype of many tumor cells in particular neoangiogenesis and
      extracellular matrix-regulated (ECM-regulated) cell proliferation, motility and
      invasiveness.

PMID- 15992170
TI  - Sphingosine-1-phosphate: an emerging therapeutic target.
AB  - Sphingosine-1-phosphate (SPP) is a polar sphingolipid metabolite that has
      received increasing attention as both an extracellular mediator and an
      intracellular second messenger. SPP is the ligand of a family of specific cell
      surface G-protein coupled receptors (GPCR), known as the endothelial
      differentiation gene-1 (EDG-1) family. These receptors, which include EDG-1, -3, 
      5, -6 and -8, regulate diverse processes including cell migration, angiogenesis,
      vascular maturation, heart development, neurite retraction and soma rounding. In
      addition, abundant evidence indicates that SPP also acts as an intracellular
      lipid messenger, regulating calcium mobilisation, cell growth and survival. The
      relative intracellular level of SPP and ceramide, another sphingolipid metabolite
      associated with cell death and cell growth arrest, is an important factor in
      determining cell fate. Changes in SPP and ceramide have been implicated in a
      number of pathological conditions in which apoptosis plays an important role,
      including cancer and neurodegenerative disorders, as well as in atherosclerosis
      and allergic responses. This review will examine the biosynthesis, metabolism and
      potential functions of SPP in diverse diseases in order to illuminate targets for
      the pharmaceutical and therapeutic manipulation of SPP levels.

PMID- 15992171
TI  - The emerging utility of animal models of chronic neurodegenerative diseases.
AB  - The two most common neurodegenerative diseases are Alzheimer's disease (AD) and
      Parkinson's disease (PD). The symptoms are caused by the initially selective
      degeneration of neuronal subpopulations involved in memory (AD) or movement
      control (PD). The cause of both diseases is unknown, but ageing is an inevitable
      risk factor. The identification of disease-associated genes was a breakthrough
      for the understanding of molecular mechanisms of neurodegeneration and has
      provided the basis for the establishment of cell culture and animal model
      systems, instrumental for target validation and drug screening. Familial AD is
      caused by mutations in the beta-amyloid precursor protein (betaAPP) and in the
      gene products responsible for its proteolytic processing, namely the presenilins.
      Transgenic mice expressing these mutant genes develop characteristic AD plaques
      in an age-dependent manner. A reduction of plaque burden and amelioration of
      cognitive decline in these animals was recently achieved by vaccination with
      amyloid beta-protein fibrils. The other hallmark lesion of AD, the
      neurofibrillary tangle, has been modelled recently in transgenic mice expressing
      mutant tau protein linked to frontotemporal dementia. PD is characterised by
      intraneuronal cytoplasmic deposits (Lewy bodies) of the PD-associated gene
      product alpha-synuclein. Transgenic expression of alpha-synuclein recreated
      hallmark features of PD in mice and fruit flies, establishing alpha-synuclein as
      PD-causing drug target. Moreover, environmental risk factors such as the
      pesticide rotenone have been used successfully to generate rodent models of PD.
      Lesion models of PD are being exploited for the development of experimental gene
      therapy and transplantation approaches.

PMID- 15992172
TI  - Sec, drugs and rock'n'roll: antibiotic targeting of bacterial protein
      translocation.
AB  - A large number of bacterial proteins are active in extracytoplasmic locations.
      Targeting and membrane translocation of the vast majority of these secretory and
      membrane polypeptides is mediated by the Sec pathway. Protein secretion requires
      the co-ordinated and sequential action of targeting factors on the cis-side of
      the membrane, a complex membrane-embedded protein translocase and maturation
      enzymes on the trans-side. Recently, significant advances in the molecular
      genetics and biochemistry of the Sec pathway have revealed that several of the
      Sec pathway components are essential for bacterial viability and/or
      pathogenicity. Moreover, several biochemical assays and structural insights have
      become available. Importantly, some of the Sec components are unique to bacteria.
      These developments raise the possibility that the bacterial protein translocase
      and other Sec pathway components could become formidable targets for
      antibacterial drug discovery.

PMID- 15992173
TI  - Combating Gram-positive pathogens: emerging techniques to identify relevant
      virulence targets.
AB  - Recent progress in microbial genome sequencing, along with functional genomics
      technologies based on gene expression, proteomics and genetics have facilitated
      the identification of significant numbers of Gram-positive virulence genes. These
      genes represent a novel and heterogeneous class of targets for antimicrobial drug
      development. This review will concentrate of the contribution of two functional
      genomics technologies, in vivo expression technology (IVET) based on gene
      expression and signature-tagged mutagenesis (STM), a genetics based technology to
      the identification of virulence genes in Gram-positive pathogens.

PMID- 15992174
TI  - A new frontier in pharmacology: the endoplasmic reticulum as a regulated export
      pathway in health and disease.
AB  - The endoplasmic reticulum (ER), the first secretory compartment of eukaryotic
      cells, co-ordinates the biogenesis and export of all membrane-bound and soluble
      cargo molecules to the cell surface. ER function is now recognised to have
      unprecedented links with signalling pathways regulating cell growth and
      differentiation and host physiology. Misfolding and aggregation of newly
      synthesised proteins in the ER or alterations in ER processing of cargo mediated
      by pathogens is responsible for a broad range of diseases including cystic
      fibrosis, emphysema and neuropathies such as Alzheimer's disease. The central,
      integrative role of the ER in determining cell physiology in health and disease
      represents an untapped area for pharmacological intervention. This review focuses
      on the potential use of pharmacological agents to modulate cargo selection,
      folding and degradation in the ER with the goal of alleviating ER export disease.
      In addition, implementation of novel technologies that utilise normal ER function
      to store and release biologically active substances of therapeutic relevance are
      presented as a new frontier in drug delivery.

PMID- 15992175
TI  - Yeast as a model system for anticancer drug discovery.
AB  - Saccharomyces cerevisiae has been used extensively as a model for higher
      eukaryotes in the study of basic cellular processes. The high degree of
      conservation in terms of sequence similarity and function has made this organism
      useful in elucidating biological pathways, both yeast and human. Among these are
      pathways responsible for DNA damage repair and cell cycle control. This review
      presents an overview of opportunities for using yeast as a model system for
      anticancer drug discovery. It covers screens directed against specific cancer
      related targets as well as contexts created by cancer-related alterations. The
      methodologies covered include pharmacological and genetic screens, as well as
      genome-wide approaches to drug target identification.

PMID- 15992176
TI  - NF-kappaB: a therapeutic target in inflammatory diseases.
AB  - The transcription factor NF-kappaB has been implicated in the pathogenesis of a
      variety of both acute and chronic inflammatory diseases. Many agents have shown
      promise and potential to abrogate NF-kappaB activity in both in vitro and in vivo
      systems. These include antioxidants, corticosteroids, proteasome inhibitors,
      arachadonic acid pathway metabolites, salicylates, molecular interventions and
      cell-permeable peptides. Unfortunately, therapies aimed at blocking its
      activation have not proven clinically feasible at this time. As the complex
      signal transduction pathways leading to NF-kappaB activation are further
      elucidated, more specific inhibitors of NF-kappaB are likely to be identified.

PMID- 15992177
TI  - Sarcoplasmic reticulum and cardiac oxidative stress: an emerging target for heart
      disease.
AB  - The sarcoplasmic reticulum (SR) is a major player in maintaining cardiac
      function, as it is intimately involved in the regulation of Ca2+-movements on a
      beat-to-beat basis. SR dysfunction due to abnormalities in SR protein content has
      been reported in different cardiac diseases such as ischaemic heart disease,
      myocardial infarction, congestive heart failure and various cardiomyopathies;
      thus the genes expressing the SR Ca2+-pump, Ca2+-channels, calsequestrin,
      phospholamban and other regulatory proteins are considered important targets for
      drug development. In our experience, ischaemic preconditioning (IP) and
      pharmacological therapies, such as anti-oxidants, beta-adrenergic receptor
      blockers, angiotensin receptor (AT-1) blockers, angiotensin converting enzyme
      inhibitors (ACE-I) and angiotensin receptor blockers are effective therapies that
      improve cardiac performance in the failing heart by improving SR function.
      Accordingly, this paper is intended to shed light on the knowledge in the field
      of cardiac therapy targeted to improve and protect SR function.

PMID- 15992178
TI  - GABA signalling: therapeutic targets for epilepsy, Parkinson's disease and
      Huntington's disease.
AB  - Temporal lobe epilepsy (TLE), Parkinson's disease (PD) and Huntington's disease
      (HD) are neurodegenerative disorders that involve disruptions in gamma-amino
      butyric acid (GABA) signalling. GABA is the major inhibitory neurotransmitter in
      the central nervous system (CNS). TLE seizures reflect excess excitation, which
      may result from local inhibitory circuit dysfunction. PD devastates the input to
      striatal GABAergic neurones and HD destroys striatal GABAergic neurones.
      Controlling GABA delivery to specific brain areas should benefit each of these
      diseases. The molecules responsible for GABA release and signalling are ideal
      targets for new therapies. In this paper, we discuss the role of GABA in the
      circuitry affected by each of these diseases and suggest potential sites for
      intervention. GABA is unique among neurotransmitters because it can be
      synthesised by either of two related enzymes. Intracellular GABA is found
      throughout the cytosol and in synaptic vesicles. GABA can be released either
      through exocytosis, or via the plasma membrane transporter. The synthesising
      enzyme probably determines the intracellular location and hence the mechanism for
      GABA release. Directing GABA synthesis, degradation, transport or receptors can
      control GABA signalling. We propose that new drugs and devices aimed at GABA
      synthesis, release and binding will offer novel and highly effective treatments
      for neurodegenerative diseases.

PMID- 15992179
TI  - Endocannabinoids Part I: molecular basis of endocannabinoid formation, action and
      inactivation and development of selective inhibitors.
AB  - The discovery of specific receptors for Delta9-tetrahydrocannabinol, the major
      psychoactive component of marijuana, opened new horizons for the possible
      therapeutic exploitation of Cannabis sativa and the cannabinoids. Endogenous
      ligands of cannabinoid receptors, the 'endocannabinoids', were found and the
      molecular mechanisms underlying their biological effects and the regulation of
      their levels are now being identified. Cause/effect relationships between
      alterations of cannabinoid receptor/endocannabinoid levels in tissues and the
      symptoms of various pathological states are starting to be revealed. These
      studies may open the way to the possible use of substances that manipulate
      endocannabinoid levels and actions, such as inhibitors of the biosynthesis and
      inactivation and receptor antagonists, as cannabinoid-based therapeutic agents
      with little or no psychotropic side effect, thus potentially fulfilling an
      ambition nurtured for almost two centuries.

PMID- 15992180
TI  - Heat shock proteins: new keys to the development of cytoprotective therapies.
AB  - All cells, from bacterial to human, have a common, intricate response to stress
      that protects them from injury. Heat shock proteins (Hsps), also known as stress
      proteins and molecular chaperones, play a central role in protecting cellular
      homeostatic processes from environmental and physiologic insult by preserving the
      structure of normal proteins and repairing or removing damaged ones. An
      understanding of the interplay between Hsps and cell stress tolerance will
      provide new tools for treatment and drug design that maximise preservation or
      restoration of health. For example, the increased vulnerability of tissues to
      injury in some conditions, such as ageing, diabetes mellitus and menopause, or
      with the use of certain drugs,, such as some antihypertensive medications, is
      associated with an impaired Hsp response. Additionally, diseases that are
      associated with tissue oxidation, free radical formation, disorders of protein
      folding, or inflammation, may be improved therapeutically by elevated expression
      of Hsps. The accumulation of Hsps, whether induced physiologically,
      pharmacologically, genetically, or by direct administration of the proteins, is
      known to protect the organism from a great variety of pathological conditions,
      including myocardial infarction, stroke, sepsis, viral infection, trauma,
      neurodegenerative diseases, retinal damage, congestive heart failure, arthritis,
      sunburn, colitis, gastric ulcer, diabetic complications and transplanted organ
      failure. Conversely, lowering Hsps in cancer tissues can amplify the
      effectiveness of chemo- or radiotherapy. Treatments and agents that induce Hsps
      include hyperthermia, heavy metals (zinc and tin), salicylates, dexamethasone,
      cocaine, nicotine, alcohol, alpha-adrenergic agonists, PPAR-gamma agonists,
      bimoclomol, geldanamycin, geranylgeranylacetone and cyclopentenone prostanoids.
      Compounds that suppress Hsps include quercetin (a bioflavinoid), 15
      deoxyspergualin (an immunosuppressive agent) and retinoic acid. Researchers who
      are cognisant of the Hsp-related effects of these and other agents will be able
      to use them to develop new therapeutic paradigms.

PMID- 15992183
TI  - Half-full or half-empty: making the message of palliative care palatable.

PMID- 15992184
TI  - End-of-life care in the nursing home.

PMID- 15992186
TI  - How to choose a site visit program.

PMID- 15992187
TI  - The nature of an ethics and law review article: the challenges of a paper on
      physician-assisted dying.

PMID- 15992188
TI  - Extending palliative care is there a role for preventive medicine?
AB  - Historically, the concept of palliative care has been limited to hospice and end
      of-life services. Recently, palliative care has been expanded to emphasize its
      integration throughout an illness. We suggest that palliative care provides an
      opportunity to prevent illness. Palliative care providers can effectively reduce
      the risk of illness in families by employing methods and strategies of preventive
      medicine. We illustrate three such cases. Patients and survivors may benefit from
      appropriate recognition and referral to prevent potential medical, social, and
      psychological problems. For preventive medicine to become fully exploited by
      palliative care providers, curricula will need to be developed. Risk assessment
      indicators of heritable and acquired conditions will define core functions of
      this educational process. Relevant topics should encompass basic preventive
      medicine methods, methods to disseminate assigned risk to the palliative care
      team, and referral mechanisms to specialists with expertise in the identified
      area(s) of concern. Opportunities to integrate preventive care into end-of-life
      services will create a new dimension for comprehensive palliative care.

PMID- 15992189
TI  - A simple standardized method for VAS measurements in terminally ill patients.

PMID- 15992190
TI  - Prognostication in hospice care: can the palliative performance scale help?
AB  - BACKGROUND: Accurate prognostication of the trajectory of an illness provides
      multiple benefits in end-of-life care. Prognostic information facilitates more
      realistic decision making regarding ongoing treatment, fosters risk-benefit
      considerations of specific interventions, and contributes to appropriate
      utilization of health care services. OBJECTIVE: The Palliative Performance Scale
      (PPS) has been used as a tool for measurement of functional status in palliative
      care. This study explores the application of the PPS as a tool for projecting
      length of stay until death or discharge in a home-based hospice program. METHODS:
      Records of 396 patients admitted to a large community-based hospice program
      between January 1, 2001, and March 31, 2001, were reviewed. PPS scores were
      evaluated for their predictive ability related to length of hospice survival and
      consideration for hospice discharge. Other variables analyzed included diagnosis,
      presence of comorbidities, and age. RESULTS: PPS scores were associated with
      length of survival. Negative-change scores were predictive of patient decline
      toward death, while stable PPS ratings over time resulted in discharge
      consideration. The tool as used by this hospice was not highly discriminating
      between the 30% to 40% scores or the 50% to 70% scores. CONCLUSION: The PPS
      scores are associated with patient length of survival in a hospice program and
      can be used in evaluating hospice appropriateness.

PMID- 15992191
TI  - Is the palliative performance scale a useful predictor of mortality in a
      heterogeneous hospice population?
AB  - BACKGROUND: Hospices provide care to patients with a wide range of prognoses, and
      must develop care plans that anticipate each patient's likely illness trajectory.
      However, the tools available to guide prognostication and care planning in this
      population have limited data to support their use. For instance, one of the most
      widely-used prognostic tools, the Palliative Performance Scale (PPS), has been
      studied primarily in inpatient settings and in patients with cancer. Its
      prognostic value in a heterogeneous US hospice population is unknown. OBJECTIVE:
      The goal of this study was to evaluate the prognostic value of the PPS as a
      predictor of mortality in a heterogeneous hospice population, and to determine
      whether it performs equally well across diagnoses and sites of care. DESIGN:
      Prospective cohort study using existing medical records. SETTING/SUBJECTS: This
      study was conducted at a large community hospice program, and included all
      patients enrolled in hospice during the study period. MEASUREMENTS: Each
      patient's PPS score was recorded at the time of enrollment and patients were
      followed until death or discharge from hospice. RESULTS: A total of 466 patients
      enrolled in hospice during the study period. The PPS score was a strong
      independent predictor of mortality (log rank test of Kaplan Meier survival curves
      p < 0.001). Six-month mortality rates for 3 PPS categories were 96% (for PPS
      scores 10-20), 89% (for PPS scores 30-40), and 81% (for PPS scores > or =50).
      Evaluation of interaction terms in Cox proportional hazards models demonstrated a
      stronger association between PPS score and mortality among nursing home residents
      and patients with non-cancer diagnoses. Analysis of the area under receiver
      operating characteristic curves demonstrated strong predictive value overall,
      with somewhat greater accuracy for nursing home residents and patients with
      noncancer diagnoses. CONCLUSION: The PPS performs well as a predictor of
      prognosis in a heterogeneous hospice population, and performs particularly well
      for nursing home residents and for patients with non-cancer diagnoses. The PPS
      should be useful in confirming hospice eligibility for reimbursement purposes and
      in guiding plans for hospice care.

PMID- 15992192
TI  - Questioning care at the end of life.
AB  - BACKGROUND: The goal of the larger study was to explore physicians' emotional
      responses to the death of their patients; this study analyzed a subset of
      physician transcripts to elucidate the construct of questioning care, which
      emerged from the larger study. OBJECTIVE: To analyzes how physicians question
      care-expressing concern, unease, or uncertainty about treatment decisions and
      practices, errors, or adverse events-as they attend dying patients. DESIGN:
      Retrospective interview study of physicians caring for randomly selected deaths
      on the medical service of a major academic teaching hospital, using qualitative
      and quantitative measures. SETTING, SUBJECTS: 188 attendings, residents, and
      interns on the internal medical services of two academic medical centers were
      part of the larger study. A subsample of 75 physician narratives was selected for
      qualitative data analysis for this study. MEASUREMENTS: Qualitative measures
      included open-ended questions eliciting physicians' stories of the most recent
      and a most emotionally powerful patient death they have experienced. Grounded
      theory was used to analyze physician narratives. Quantitative instruments
      measured physician attitudes toward end-of-life care and responses to the most
      recent and most emotional patient death. RESULTS: Physicians question care more
      frequently in most emotional deaths (42%) than in most recent deaths (34%).
      Physicians question communication with patients and families and within medical
      teams, medical judgment and technique, standards of practice, and high-risk
      treatments, often assigning responsibility for medical management they perceive
      as inappropriate, futile, overly aggressive, or mistakes in judgment and
      technique. Responsibility ranges from the distal (the culture of medicine) to the
      proximal (personal). Frustration, guilt, and anger are more frequently expressed
      in these narratives when care is questioned. CONCLUSIONS: A typology of
      questioning care emerged from these physicians' narratives that parallels and
      reflects recent and classic research on medical error and the culture of
      medicine. Physicians' questions about care can contribute to designing training
      experiences for residents and to improving the quality of systems that affect
      patients' experiences at life's end and physicians' experiences in caring for
      dying patients.

PMID- 15992193
TI  - Are we referring patients to hospice too late? Patients' and families' opinions.
AB  - BACKGROUND: Patients typically receive hospice care only in the last days or
      weeks of life, and there is widespread agreement among experts that patients
      enroll in hospice too late. However, it is not known whether patients and their
      families believe that they are enrolling in hospice too late. DESIGN: Prospective
      interview study. SETTING: Not-for-profit, Medicare-certified hospice. PATIENTS:
      Patients and families recruited at consecutive hospice enrollment visits.
      MEASUREMENTS: Interviews at the time of hospice enrollment and 1 month after
      death or discharge from hospice assessed patients' and families' perceptions of
      the timing of hospice enrollment ("too soon," "too late," "at about the right
      time"). RESULTS: Interviews were conducted at 274 enrollment visits. Very few
      patients (1/85; 1%) and family members (12/261; 5%) said that they believed they
      were enrolling in hospice too late. In follow-up interviews with families after
      the patient's death or discharge, families were more likely to believe that
      enrollment was too late (n = 38/218; 17%; sign test p < .001). Families who
      believed they had enrolled too late had shorter lengths of stay in hospice
      compared to those who said that enrollment was too soon or at the right time
      (median 10 vs. 24 days; rank-sum test p < 0.001). CONCLUSION: Despite late
      enrollment in hospice and very short lengths of stay, most patients and families
      believe that they are enrolling in hospice at the right time.

PMID- 15992194
TI  - Temporal distribution of deaths in cancer patients during the day in different
      settings.
AB  - BACKGROUND: All living organisms perform their functions normally according to
      circadian rhythms. Certain diseases, such as ischemic heart disease and asthma,
      produce symptoms that are distributed during the day in a nonrandom fashion.
      Chronomodulated therapy with some regimens of chemotherapy and other drugs
      produce better results than traditional schedules. Even death is not evenly
      distributed during the day. Significant differences in the time of death through
      the day could influence the work planning and care activities. OBJECTIVE: To
      determine whether timing of death from a population of cancer patients admitted
      at our Oncology Institute varied during the day and according to different
      settings: at home (H), at the palliative care unit (PCU), and at other services
      (OS) of the hospital. Comparing the timing of deaths from different settings can
      give some clues about the possible existence of a circadian rhythm and the
      influence of external circumstances in the time of death of cancer patients.
      DESIGN: We conducted a retrospective study of the records of time of death at the
      different settings. RESULTS: The study involved 772 patients from the PCU and 997
      from OS who died between May 25, 1996, and May 24, 2000, and 347 patients who
      died at H between April 1, 1999, and December 31, 2001. A statistically
      significant difference was found in the distribution of time of death in patients
      at the PCU (p <.001), but not at OS or at H. There were two peaks between 08:00
      and 10:00 and between 00:00 and 02:00, and one trough between 04:00 and 08:00.
      This suggests that a temporal variation occurs in the time of death of cancer
      patients dying in the PCU, but not in other settings. CONCLUSIONS: The clinical
      relevance of the results obtained in this study would depend on the amplitude of
      the eventual variation detected in the number of deaths during the day.
      Therefore, although there was a statistically significant variation at the time
      of death during the day, its amplitude is not high enough to make it clinically
      significant. The differences observed among the various settings suggest that,
      even if circadian rhythms exist at the time of death in cancer patients, external
      factors can overcome these rhythms.

PMID- 15992195
TI  - Perspectives of elderly veterans regarding communication with medical providers
      about end-of-life care.
AB  - OBJECTIVE: To explore patients' perspectives concerning communication with
      medical providers about end-of-life (EOL) care. DESIGN: Cross-sectional survey
      involving semistructured interviews. SETTING: Outpatient primary care clinic of a
      large, urban Veterans Affairs (VA) Medical Center. PARTICIPANTS: Male and female
      veterans who were 60 years or older, ambulatory, able to speak and read English,
      residing in the community, receiving outpatient care from the VA, not acutely ill
      (i.e., not hospitalized or in obvious distress), and not cognitively impaired.
      METHODS: During audiotaped interviews to assess understanding of advance
      directive concepts, all 30 participants were asked what advice they would give
      medical students or trainees about how to discuss EOL care with patients. The
      audiotapes of their open-ended responses were transcribed, coded, and examined
      using qualitative content analysis, a systematic and replicable technique to
      uncover meaning by detecting commonalities and regularities of speech. RESULTS:
      Seven essential elements of advice for medical providers emerged: engage in
      strategies to ensure patient understanding (mentioned by 30% of participants),
      communicate honestly and truthfully (27%), develop a compassionate bedside manner
      (27%), treat others as you would want to be treated (20%), provide empathic care
      (20%), take the time needed to communicate (20%), and determine patient
      information and decision-making preferences (17%). CONCLUSIONS: Effective EOL
      discussions with patients require attention to the content, process, and
      perception of patient-provider communication.

PMID- 15992196
TI  - End of life in nursing homes: connections between structure, process, and
      outcomes.
AB  - PURPOSE: This study was a prospective, in-depth exploration of the experience of
      dying in two nursing homes from the perspective of residents, staff, and family
      members. DESIGN AND METHODS: A qualitative, case study design was used. Formal
      and informal interviews, participant observation, and document review were the
      primary data collection methods. A total of 56 declining residents were followed
      until death or for 6 months, whichever occurred first. RESULTS: The intimate
      linkages between structure, process, and outcome were evident in both nursing
      homes. The two homes had contrasting institutional philosophies, reflected in
      staffing and environment (structure) and processes of care. Processes included
      different patterns of planning, communication, and decision making. Most
      importantly, outcomes (residents' satisfaction with care and quality of life
      while approaching death) were substantively different. IMPLICATIONS:
      Institutional philosophy and leadership permeate all aspects of care. A
      compliance- centered, deficiency-free approach to assessing quality of care is
      not sufficient to address the needs of declining residents. A client-centered
      philosophy that embraces "caring for dying people," combined with integrated care
      planning, contributes to improved resident outcomes.

PMID- 15992197
TI  - Enhancing end-of-life care in nursing homes: Palliative Care Educational Resource
      Team (PERT) program.
AB  - BACKGROUND: By the middle of this century, approximately 40% of people who will
      die from chronic illness are expected to do so in a nursing home. This trend will
      create challenges for nursing homes to ensure that staff possess the necessary
      knowledge and skills to care for dying residents. OBJECTIVE: The purpose of this
      paper is to describe the development and evaluation of a comprehensive curriculum
      called Palliative Care Educational Resource Team (PERT), which is designed to
      enhance end-of-life (EOL) abilities of nursing assistants and licensed nurses
      working in nursing homes. SUBJECTS: Sixty-one nursing assistants and 108 licensed
      nursing staff from 44 facilities have participated in PERT. Subjects were
      recruited in three successive cohorts, each targeting a different geographic
      area. MEASUREMENTS: Program evaluation included multiple tools evaluating
      participants' knowledge, skills, and confidence in providing EOL care. RESULTS:
      Evaluation of outcomes revealed significant increases in EOL knowledge, self
      evaluation of EOL skills, and supervisors' evaluations of participants' EOL care.
      CONCLUSIONS: These results show that the PERT Program is an effective means to
      enhance the palliative care expertise of nursing home staff. In addition to
      describing the PERT program and its evaluation, suggestions for implementing
      similar programs are included in this paper.

PMID- 15992198
TI  - Factors associated with self- and caregiver report of pain among community
      dwelling persons with dementia.
AB  - BACKGROUND: Among cognitively intact patients, self- and caregiver report of
      patient pain has been associated with worse psychological health for both the
      patient and caregiver. Little existing research examines factors associated with
      patient self-report of pain and caregiver report of patient pain among community
      dwelling persons with dementia. OBJECTIVE: To identify patient and caregiver
      factors associated with self- and caregiver report of patient pain among
      community-dwelling persons with dementia. DESIGN: Cross-sectional analysis of a
      longitudinal study using structured interviews with dementia patients and their
      family caregivers. SETTING AND SUBJECTS: Urban outpatient geriatrics clinics
      affiliated with a university hospital. Dyads composed of dementia patients and
      their family caregivers were approached prior to routine clinic visits to
      participate in the study. MEASUREMENTS: Relevant patient measurements included
      self-report of pain; cognitive, functional, and comorbidity assessments; a screen
      for depression; and demographic information. Relevant caregiver measurements
      included their report of patient pain and agitation, screens for depression and
      strain, and demographic information. RESULTS: Of 115 dyads, 37 patients (32%) and
      57 caregivers (53%) reported the patient to be in pain. No patient or caregiver
      factors were significantly associated with patient self-report of pain. In the
      univariate analysis, caregiver reports of patient pain were associated with the
      patient not being depressed (p = .036), caregiver reports of patient agitation (p
      = .038), higher level of education in the caregiver (p = .029), and caregiver
      depression (p = .019). In multivariate logistic regression analyses, caregiver
      depression and patient agitation remained significantly associated with caregiver
      report of patient pain. CONCLUSIONS: In community-dwelling persons with dementia,
      self-report of pain was not associated with any other variables measured,
      suggesting that pain should be assessed through direct self-report and treated
      accordingly. Caregiver report of patient pain was associated with both caregiver
      report of patient agitation and caregiver depression. These findings suggest that
      clinicians may need to routinely assess patient pain, patient agitation, and
      caregiver depression. More research is needed to understand the relationship
      between these conditions.

PMID- 15992199
TI  - A quality improvement intervention to increase palliative care in nursing homes.
AB  - CONTEXT: Death is common in nursing homes, but access to palliative care is
      limited. OBJECTIVE: To test whether a quality improvement (QI) intervention in
      nursing homes increases hospice, pain management, and advance care planning.
      DESIGN AND SETTING: The QI intervention was tested in seven nursing homes using a
      prepoststudy design. Two additional nursing homes served as control sites.
      PARTICIPANTS: Nine nursing homes serving 1169 residents. INTERVENTION: The
      intervention included recruitment and training of Palliative Care Leadership
      Teams in each facility, followed by six technical assistance meetings for team
      members. Hospice providers delivered six educational sessions for all nursing
      home staff using a structured curriculum. Teams received feedback of performance
      data on hospice enrollment, pain management, and advance care planning at 0, 3,
      and 6 months. MAIN OUTCOME MEASURES: Percentage of residents receiving hospice or
      palliative services, pain assessment, pain treatment among residents in pain, and
      documented advance care planning discussions. RESULTS: Intervention facilities
      increased hospice enrollment from 4.0% of residents at baseline to 6.8%
      postintervention (p = .01) and increased pain assessments from 18% to 60% (p <
      .001). Among resident in pain, orders for nonpharmacologic pain treatments
      increased from 15% to 35% (p < .001), but pain medication use did not change.
      Residents with in-depth discussions about end-of-life care increased from 4% to
      17% (p < .001). There were no significant changes in control sites. CONCLUSIONS:
      A quality improvement intervention was effective in increasing hospice
      enrollment, pain assessment, nonpharmacologic pain treatment, and advance care
      planning discussions.

PMID- 15992200
TI  - End-of-life care and African Americans: voices from the community.
AB  - BACKGROUND: In 1997, the Institute of Medicine called for reform, improved
      quality and expanded research in end-of-life care. Yet little empirical
      information about preferences of African Americans has been documented. A
      community-campus partnership was formed to guide a needs assessment related to
      end-of-life care in a Southern, urban, African American community. This paper
      presents focus group findings related to end-of-life and palliative care.
      METHODS: A qualitative design of multiple-meeting focus groups was used to
      explore experiences, preferences, needs, and feelings expressed by family members
      with at least one relative who had died in a hospital (group 1) or at home (group
      2). Sessions were taped and transcribed; themes were identified using systematic
      analytic procedures. RESULTS: Thematic analysis revealed key concerns related to
      health care provider communications about end-of-life care and dying. Positive
      communications empowered and showed respect for patients and family members and
      recognized the importance of their spiritual beliefs; informed them about
      resources available to assist dying at home; and, for patients dying in the
      hospital, treated them with nurturing, compassion, and diligent monitoring of the
      patient's medical status and needs. Other themes related to end-of-life care
      issues include preparation, planning, and access. A table of quotes from
      participants is available from the corresponding author. CONCLUSIONS: Findings
      suggest important clinical implications for clinicians and other health
      professionals. These voices from the community remind us of the heterogeneity in
      needs and preferences and challenge us to listen and tailor communication to each
      patient and their families.

PMID- 15992201
TI  - Medical care at the end of life: views of African American patients in an urban
      hospital.
AB  - BACKGROUND: Although one goal of end-of-life care is to honor the wishes and
      needs of patients, little research has been done to characterize what is
      important to seriously ill African American patients at the end of life.
      OBJECTIVE: To characterize the views of seriously ill African American patients
      toward end-of- life care. DESIGN: A qualitative study using semistructured, in
      depth interviews. SETTING AND PARTICIPANTS: Patients in a large, urban, public
      hospital who are facing a serious illness. RESULTS: Twenty-three African American
      patients were interviewed. Although most acknowledged a point at which they would
      want to cease aggressive care, some equated this with giving up. Most subjects
      expressed that the end of life was in God's hands. Many expressed a concern to be
      free of pain and suffering. Few saw a significant role for the physician at the
      end of life. Some had expressed their wishes for care to a family member. Others
      thought such discussions were unnecessary because a family member would make
      decisions or because death was not imminent. Subjects raised concerns about trust
      in the physician and the burden of end-of-life discussions. CONCLUSIONS: African
      Americans in an urban, public hospital who are facing a severe illness have clear
      desires for care at the end of life and are willing to discuss their views at
      length. Such discussions should explore patients' desire for aggressive care,
      consider spiritual views and the importance of family in end-of-life decisions,
      and consider that some patients will not believe such discussions are necessary.

PMID- 15992202
TI  - "Lost to follow-up": ethnic disparities in continuity of hospice care at the end
      of life.
AB  - BACKGROUND: Hospice has become the major provider of comprehensive end-of-life
      care in the United States, but is underutilized by African American patients. It
      is likely that whatever factors are responsible for lower rates of hospice
      utilization among African Americans also lead to lower rates of return to hospice
      after discharge, but this is not known. OBJECTIVE: To determine whether African
      American patients who leave hospice are less likely to return before death.
      DESIGN: Retrospective cohort study. SETTING: University-affiliated hospice.
      PARTICIPANTS: All patients discharged after a first admission. MEASUREMENTS: All
      patient characteristics were defined by abstraction of electronic medical records
      at the time of hospice discharge. RESULTS: Of 358 discharged patients, 98 (27%)
      were decertified and 260 (73%) left voluntarily. Ninety-six patients returned to
      hospice during the study period. In bivariate analysis, African Americans were
      less likely to return than were other patients (odds ratio (OR) 0.47, 95% CI:
      0.28-0.80; p = .005). In a multivariable logistic regression model, African
      American ethnicity was independently associated with a decreased likelihood of
      return. CONCLUSIONS: Ethnic disparities in hospice utilization may extend even to
      those patients who do enroll in hospice. African Americans who leave hospice
      during their first admission and their families may be less likely to have access
      to the comprehensive services that hospice programs provide near the end of life,
      including intensive nursing care, pain and symptom management, and education.

PMID- 15992203
TI  - Ethics and law: physician-assisted dying.

PMID- 15992204
TI  - Enhancing our understanding of the impact of transition to end-of-life
      caregiving.

PMID- 15992205
TI  - Final transitions: family caregiving at the end of life.
AB  - BACKGROUND: This study aimed to understand how caregivers make the transition to
      end-stage caregiving and to illuminate its unique aspects using a stress process
      model. METHODS: Qualitative in-depth interviews were conducted with 74 caregivers
      of a family member who had been receiving hospice care for at least 2 weeks.
      Interviews were tape recorded, transcribed, and coded for emergent themes using
      constant comparative analysis. RESULTS: End-stage caregiving was characterized in
      the sample as (1) comprehension of terminality (the interrelationship of
      information, physical and cognitive decline, and personality change and role
      losses), (2) near-acute care, (3) executive functions, and (4) final decision
      making. The comprehension of terminality emerged from three interrelated
      experiences: receiving and assimilating concrete information about the illness,
      observing the progression of the disease, and observing the personality change
      and role loss. The primary stressors (unique end-stage caregiving tasks) were
      providing near-acute care, assuming an executive function, and beginning and
      final decision making. The secondary stressors were family role conflict, work
      conflict, and financial strain. Resources, such as intrinsic and extrinsic
      religious and faith practices and social support, were identified. Negative
      outcomes included intense emotional responses, and positive outcomes included
      heightened development of meaning making. CONCLUSION: The findings suggest that
      palliative care professionals have important opportunities to provide information
      and support to family caregivers during the final stages of the patient's
      terminal illness.

PMID- 15992206
TI  - Discussing organ donation with families; declaring brain death: the neurological
      criteria.

PMID- 15992207
TI  - Father's day.

PMID- 15992208
TI  - Taking risks.

PMID- 15992211
TI  - Implementing institutional change: an institutional case study of palliative
      sedation.
AB  - Palliative sedation is used in the rare patient who has intractable distress at
      the end of life. Implementation of palliative sedation, however, may meet
      resistance from various clinicians and other hospital staff. To ensure that our
      patients had access to this important treatment modality, we found it necessary
      to engage in a process of institutional change that resulted in acceptance of the
      use of palliative sedation in the non-ICU setting.* In this paper, we will review
      the processes we found to be successful in hopes that they will also be
      efficacious for others wishing to produce similar change within their
      institutions. We first will review the theoretical foundations described in
      organizational development and change management literature. Next we describe our
      implementation strategies (including education, multidisciplinary alliances, and
      the development and approval of a practice guideline). Finally, we discuss in
      detail the role of interpersonal interactions. Three clinical cases are used to
      demonstrate the change in attitudes, processes, and outcomes.

PMID- 15992217
TI  - Comfort measures only.

PMID- 15992219
TI  - A test of the systems analysis underlying the scientific theory of Ayurveda's
      Tridosha.
AB  - A previous paper hypothesized that the tridosha of Ayurveda--vata, pitta, and
      kapha--constitute regulatory systems respectively controlling input/output,
      turnover, and storage; functions systems analysis identifies as fundamental to
      all open systems. This would make them universal properties of all living
      organisms, as Ayurveda itself maintains. This paper proposes independent
      scientific evidence for the proposed identification of the doshas and for the
      systems analysis on which it is based. In particular, it points to coenzyme A, a
      key component of fatty acid metabolism. Its universal presence in all cells
      implies that it is an evolutionary invariant ant that the biochemical pathway on
      which it lies must be exceptionally significant. The systems analysis shows that
      the pathway connects the cellular functions of energy turnover and energy
      storage, fundamental to the overall strategy of cell regulation. This, combined
      with the requirement for the pathway's close regulation, makes it effectively
      impossible to replace coenzyme A by a combination of simultaneous mutations or
      sequence of mutations and it should indeed remain invariant during evolution. The
      universality of coenzyme A is therefore consistent with its identified role, and
      supports the systems analysis identifying the doshas. Their systems functions
      survive developmental transformations of evolution with recognizable continuity.
      By virtue of that, vata, pitta, and kapha can be identified with them in all
      species.

PMID- 15992220
TI  - Energy healing training and heart rate variability.

PMID- 15992221
TI  - Indigenous Hawaiian nonmedical and medical use of the kukui tree.

PMID- 15992222
TI  - The association between the DRD2 TaqI A polymorphism and smoking cessation in
      response to acupuncture in Koreans.
AB  - OBJECTIVES: The response to acupuncture is presumed to differ with the
      individual; this variation might be due to genetic differences. Therefore, we
      examined whether the DRD2 TaqI A polymorphism is associated with the response to
      acupuncture in the treatment of smoking cessation in a Korean population.
      SUBJECTS: A total of 231 healthy Korean male smokers participated in this study.
      INTERVENTIONS: The subjects underwent three manual auricular acupuncture
      treatments in one week. DESIGN AND OUTCOME MEASURES: After 1 week, high and low
      responders to the acupuncture treatment were selected according to their
      cigarette consumption and the desire to smoke. A DRD2 TaqI A restriction enzyme
      fragment length polymorphism (RFLP) study examined genomic DNA extracted from
      blood samples. RESULTS: The proportions of high, intermediate, and low responders
      were 28.6, 55.4, and 16.0%, respectively. The RFLP study showed that the
      distribution of the DRD2*A genotype and allele frequencies differed significantly
      between the high and low responders (chi(2) test, p = 0.031 and 0.016,
      respectively), and that high responders had a higher DRD2*A2 allele frequency
      than low responders. CONCLUSIONS: Our findings suggest that DRD2 TaqI A
      polymorphism is related to acupuncture response in smoking cessation treatment.

PMID- 15992223
TI  - Transcutaneous electrical acupoint stimulation versus ondansetron in the
      prevention of postoperative vomiting following pediatric tonsillectomy.
AB  - OBJECTIVES: Postoperative retching and vomiting is an important cause of
      morbidity that may lead to patient discomfort, distress, and complications.
      Stimulation of acupuncture points has been shown to be effective in the
      prevention as well as treatment of PONV. The current treatments of choice are the
      5-hydroxytryptamine type 3-antagonists, such as ondansetron. We aimed to evaluate
      the efficacy and side-effects of either transcutaneous electrical acupoint
      stimulation (TEAS) or Ondansetron compared to a control group receiving no
      treatment in the prevention of postoperative retching and vomiting. SUBJECT AND
      DESIGN: This randomized, controlled, prospective study was carried out in a group
      of 90 children (in three equal randomly assigned groups), aged between 4 and 12
      who underwent tonsillectomy under general anesthesia. In the first group,
      electrical stimulation via surface electrodes on acupoints Neiguan and Shangwan
      was performed (20 Hz, 5 minutes). The second group received a single dose of
      Ondansetron (0.15 mg . kg(-1)). No treatment was given to the control group.
      OUTCOME MEASURES: The frequency of retching and vomiting attacks and side-effects
      were noted on the day of surgery in the postanesthesia care unit and the day
      surgery care unit, on the day of surgery after discharge, and on the first day
      after surgery. A satisfaction scale was completed by each family. RESULTS: There
      was a significant difference between the treatment groups and the control group
      in the incidence of emetic episodes occurring in the day surgery care unit and on
      the day after discharge (p < 0.001). In the ondansetron group, side-effects were
      seen in more patients than in the other groups (p < 0.001). The satisfaction
      scores of the parents were greater in the treatment groups than in the control
      group (p < 0.05). CONCLUSION: Application of TEAS on sedated children is an easy,
      painless, reliable and effective method for the prophylaxis of postoperative
      retching and vomiting in pediatric tonsillectomy.

PMID- 15992224
TI  - Variability in the traditional Chinese medicine (TCM) diagnoses and herbal
      prescriptions provided by three TCM practitioners for 40 patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To ascertain if previous findings of low levels of agreement of
      Traditional Chinese Medicine (TCM) pattern diagnoses made by TCM practitioners in
      patients with rheumatoid arthritis (RA) were a function of practitioner
      differences or would be replicated with a different sample of clinicians, and to
      examine the relationship between TCM diagnosis and herbal treatment plans.
      DESIGN: A prospective survey. SETTING: General clinical research center,
      University of Maryland Hospital System, Baltimore, MD. SUBJECTS: Forty (40)
      patients with RA. PRACTITIONERS: Licensed acupuncturists with at least 5 years'
      experience and education in Chinese herbs. METHODS: Three (3) TCM practitioners
      examined the same 40 RA patients separately, following the traditional Four
      Diagnostic Methods. Patients filled out questionnaires and physical examinations,
      including observations of the tongue and palpation of radial pulse, were
      conducted by the 3 practitioners. Each practitioner then provided both a TCM
      diagnosis and an herbal prescription. These diagnoses/prescriptions were examined
      with respect to the rate of agreement among the 3 practitioners. RESULTS: The
      average agreement with respect to the TCM diagnoses among the 3 TCM practitioners
      was 31.7 % (range, 27.5-35%). The degree to which the herbal prescriptions agreed
      with textbook recommended practice for each TCM diagnosis was 91.7% (range, 85
      100%). The most commonly used TCM assessments in arriving at these diagnoses were
      inquiry about factors affecting pain and pulse diagnosis. No statistically
      significant differences were found between this study and our previous study
      regarding the level of agreement on TCM diagnosis. CONCLUSION: The average
      agreement of the diagnoses provided by 3 TCM practitioners was at the same low
      level as previously reported. No association was found between the diagnostic
      methods used and the consistency of diagnosis. Both studies, however, found a
      high degree of consistency between the TCM pattern diagnoses provided and the
      herbal treatment plans made as a result of those diagnoses.

PMID- 15992225
TI  - Effects of nitric oxide and noradrenergic function on skin electric resistance of
      acupoints and meridians.
AB  - OBJECTIVES: The objectives of this study were to determine the effects of L
      arginine-derived nitric oxide (NO) synthesis and noradrenergic function on skin
      electrical resistance of acupoints and meridians. DESIGN: Experiments were
      performed on male Sprague-Dawley rats anesthetized with sodium pentobarbital. Low
      skin-resistance points (LSRP; BL 56, PC 6, CV 17), non-LSRP positions (along the
      meridians), and non- LSRP, non-meridian control positions (adjacent to but not
      along the meridians) were determined on the skin surface by measurements of the
      skin stimulus-evoked electrical currents. The effects of L-arginine-derived NO
      synthesis and noradrenergic function on the currents, representing skin
      electrical resistance, were examined in the LSRP, non-LSRP, and non-meridian
      control points. RESULTS: The skin stimulus-evoked electrical currents at BL 56
      (36.4 +/- 1.4 microA), PC 6 (35.4 +/- 1.2), and CV 17 (33.1 +/- 1.4) were
      significantly higher than those in non-LSRP and non-meridian control positions (p
      < 0.01, n = 7). The currents were consistently increased after repeated
      stimulation along the skin as a function of time. Intravenous injections of L
      arginine (3 mg/kg, 10 mg/kg, and 30 mg/kg) and 3-morpholinyl-sydnoneimine (SIN-1;
      1 microg/kg, 3 microg/kg, and 10 microg/kg) produced dose-dependent increases in
      the currents (p < 0.05, n = 5-6), but currents were not altered by injections of
      D-arginine (3 mg/kg, 10 mg/kg, and 30 mg/kg). Stimulus-evoked increases in
      currents were blocked by intravenous injections of either N (G)-propyl-L-arginine
      (NPLA, 3 mg/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or
      guanethidine (3 mg/kg), a noradrenergic blockade. CONCLUSIONS: This is the first
      evidence showing that L-arginine-derived NO synthesis and noradrenergic
      transmission modify the skin electric conductance of LSRP. L-Arginine-derived NO
      synthesis appears to mediate noradrenergic function on skin sympathetic nerve
      activation, which contributes to low resistance characteristics of acupoints and
      meridians.

PMID- 15992226
TI  - Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and
      Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9.
AB  - OBJECTIVE: To study the potential of three top-selling herbal products, Ginkgo
      biloba, Echinacea purpurea, and Serenoa repens to inhibit the in vitro enzymatic
      activity of three of the most important drug metabolizing enzymes, cytochrome
      P450 (CYP) 3A4, 2D6, and 2C9. METHODS: High throughput CYP inhibition screening
      was used to test the inhibitory capacity of extracts of commercially available
      herbal medications on the metabolism of CYP enzyme substrates. RESULTS: S. repens
      showed potent inhibition of the metabolic activity of all three CYPs tested. The
      effects of G. biloba and E. purpurea varied. E. purpurea demonstrated mild
      inhibition of CYP3A4 activity with 7- benzyloxy-4-trifluoromethylcoumarin (BFC)
      as the model substrate, but mild inducing effects in the presence of the model
      substrate resorufin benzyl ether (BzRes). Little effect on CYP2D6 and moderate
      inhibition of CYP2C9 was seen with both E. purpurea and G. biloba. G. biloba also
      showed mild-to-moderate inhibition of CYP3A4 depending on the model substrate.
      CONCLUSIONS: The inhibitory capacity of herbal products varies depending on the
      concentrations of the model substrate and the herbal extract, as well as the
      identity of the model substrate, as demonstrated by the varied effects of CYP3A4
      enzymatic activity with different model substrates. The potential for strong
      adverse interactions exists for Serenoa repens, which was a potent inhibitor of
      all three CYPs examined. Physicians are encouraged to advise patients of the
      risks of combining herbal products with prescription medications.

PMID- 15992227
TI  - Coping in women with breast cancer in complementary and conventional care over 5
      years measured by the mental adjustment to cancer scale.
AB  - OBJECTIVE: Many patients with cancer, women more often than men, use
      complementary and alternative medicine (CAM) and care. Our aim was to examine
      coping over 5 years (November 1995 to January 1999) in two samples of women with
      breast cancer who were treated with anthroposophic care or conventional medical
      treatment. The present study is part of a larger study of the outcome of
      anthroposophic care for women with breast cancer. DESIGN: A nonrandomized
      controlled trial design was used with individual matching and repeated
      measurements on six occasions (at admission, 1 month, 3 months, 6 months, 1 year,
      and 5 years). The matching was based on the following variables: stage of disease
      at entry, age, treatment during the 3 months before entering the study, and
      prognosis. SETTING: An anthroposophic hospital and conventional hospitals in
      Sweden. SUBJECTS: Sixty (60) women treated with anthroposophic medicine and 60
      women from an oncology outpatient department participated. Forty-nine (49) women
      in anthroposophic care and 51 in the outpatient group survived 1 year; 26 women
      in anthroposophic care and 31 in the outpatient group survived 5 years.
      INTERVENTION: An anthroposophic care program. OUTCOME MEASURE: Coping was
      measured using the Mental Adjustment to Cancer scale. Repeat measures of analysis
      of variance (ANOVA) were used for within-group comparisons, and effect size (ES)
      was used for between-group comparisons. RESULTS: The women in anthroposophic care
      showed more passive and anxious coping on admission, but this decreased over
      time. In the women in anthroposophic care, there were small ES improvements in
      fighting spirit and passive, anxious coping at 4 of the measured timepoints
      compared to admission. CONCLUSION: The choice of anthroposophic care could be
      seen as a possible way to cope with emotional distress in this group of women
      with breast cancer.

PMID- 15992228
TI  - Patients' perceptions of primary care physicians' participatory decision-making
      style and communication about complementary and alternative medicine for
      arthritis.
AB  - OBJECTIVE: The purpose of this study was to examine: (1) which patient
      demographics were related to whether patients rated their family physicians as
      using a participatory decision-making style, and (2) whether arthritis patients
      who reported using complementary and alternative medicine (CAM) were more likely
      to report discussing CAM use with their providers if they saw family physicians
      rated with participatory decision-making styles. METHODS: A survey that asked
      about health status, demographics, physician use of a participatory decision
      making style, and medical skepticism was sent to 2178 patients with arthritis who
      attended 16 different family practice sites that were part of a research network
      in rural and urban North Carolina. Generalized estimating equations were used to
      analyze the data. RESULTS: Younger and more educated patients were more likely to
      rate their family physicians as using participatory styles. In all, 71% of
      patients who reported having used one or more CAM strategy reported having
      discussed it with their physicians. Patients who rated their health as worse,
      reported using more categories of CAM, and rated their physicians as being using
      participatory styles were more likely to tell their physicians about their CAM
      use. CONCLUSION: Our findings suggest that if providers use more participatory
      styles with patients and involve them when making treatment decisions; patients
      will tell providers more about what they are doing for their health.

PMID- 15992229
TI  - Positive well-being changes associated with giving and receiving Johrei healing.
AB  - OBJECTIVES: The aim of this study was to examine the effects of giving and
      receiving Johrei, a spiritual energy healing practice, on measures of well-being.
      METHODS: Participants (N = 236) rated 21 items pertaining to feelings plus an
      overall well-being measure, before and after a Johrei session. RESULTS: Receivers
      experienced a significantly greater decrease in negative emotional state than
      givers; however, givers and receivers experienced a comparable increase in
      positive emotional state and overall well-being. CONCLUSIONS: The practice of
      Johrei and other energy and spiritual healing techniques, may have positive
      health effects for givers as well as receivers. Future research examining
      different energy and spiritual healing practices (for example, Reiki and
      Therapeutic Touch) and using various control groups (for example, treatment-naive
      subjects instructed to "send loving energy") can explore the generality and
      mechanisms underlying these apparently robust effects.

PMID- 15992230
TI  - Complementary and alternative medicine for low-back pain in pregnancy: a cross
      sectional survey.
AB  - OBJECTIVE: To identify common treatments used for low-back pain (LBP) during
      pregnancy. DESIGN: A two-part anonymous survey. SETTING/LOCATION: New Haven,
      Connecticut. SUBJECTS: Pregnant women and providers of prenatal health care
      (nurse educators, nurse midwives, and obstetricians). RESULTS: We found that the
      majority of pregnant women who participated in our survey (61.7%) reported that
      they would accept complementary and alternative medicine (CAM) therapy as
      treatment for LBP during pregnancy. Similarly, 61% of providers of prenatal
      health care in our sample reported that they would consider using CAM as
      treatment for LBP during pregnancy. Massage (61.4%), acupuncture (44.6%),
      relaxation (42.6%), yoga (40.6%), and chiropractic (36.6%) were the most common
      CAM therapies recommended for LBP in pregnancy by the providers of prenatal
      health care in our sample. CONCLUSIONS: This two-part survey study found that
      both providers of prenatal health care and pregnant women in New Haven county are
      likely to use CAM treatments for pregnancy-induced LBP. Further investigation
      should focus on whether it is a nationwide phenomenon, as well as if various CAM
      therapies are an efficacious treatment for LBP during pregnancy.

PMID- 15992231
TI  - Meditation reduces sympathetic activation and improves the quality of life in
      elderly patients with optimally treated heart failure: a prospective randomized
      study.
AB  - OBJECTIVE: We tested whether meditation can reduce sympathetic activation,
      evaluated by norepinephrine blood levels (NE), and improve quality of life in
      elderly persons with congestive heart failure (CHF). DESIGN AND SETTING: This was
      a prospective, randomized study conducted from April 2000 to October 2001 in an
      ambulatory care teaching hospital in Sao Paulo, Brazil. SUBJECTS: We studied 19
      patients with CHF, 74.8 +/- 6.7 years old, receiving diuretics, optimal doses of
      an angiotensin-converting enzyme inhibitor or angiotensin II inhibitor, maximum
      tolerated carvedilol dose (23.1 +/- 13.6 mg) and spironolactone 25 mg (10
      patients). INTERVENTIONS: After 2 months of optimal treatment with carvedilol,
      patients were randomized into two groups. The meditation group (M) was provided
      an audiotape, 30 minutes long, to listen to at home, twice a day, for 12 weeks,
      plus a weekly meeting. The control group (C) just had weekly meetings. MAIN
      OUTCOME MEASURES: We determined before and after 14 +/- k1 weeks, NE (in pg/mL);
      quality of life with the Minnesota Living with Heart Failure Questionnaire
      (MLWHFQ); VO2 and VE/VCO2 slope by cardiopulmonary exercise testing; left
      ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume
      index (LVDDi) measured by echocardiography. RESULTS: Meditation reduced NE (mean
      +/- SEM) from 677.7 +/- 96.6 to 387.1 +/- 39.1 pg/mL (p = 0.008) in M versus
      491.4 +/- 35.9 to 470.6 +/- 31.2 (p = 0.34) in C; improved MLWHFQ total score
      (mean +/- SEM) from 33.2 +/- 6.6 to 21.6 +/- 6.8 points (p = 0.02) in M versus
      18.4 +/- 8.0 to 25.1 +/- 8.9 (p = 0.41) in C; and reduced the VE/VCO2 slope (mean
      +/- SEM) from 31.2 +/- 3.0 to 28.2 +/- 2.6 (p = 0.04) in M versus 28.4 +/- 2.7 to
      28.8 +/- 2.6 (p = 0.24) in C. No changes occurred in LVEF, LVDDi, and VO(2).
      CONCLUSIONS: In elderly patients with optimally treated CHF, meditation reduced
      NE, improved quality of life, and reduced the VE/VCO(2) slope. Our results
      support the possible role of meditation as a new hope in the treatment of CHF.

PMID- 15992232
TI  - The patient: a novel source of error in clinical temperature measurement using
      infrared aural thermometry.
AB  - INTRODUCTION: The vital signs are an important component of patient assessment.
      With respect to body temperature; there has been a move away from mercury-in
      glass thermometers toward the relatively inexpensive, safer to use infrared
      tympanic, auricular, or ear thermometer. Although already in widespread use, the
      reliability of these devices has increasingly been called into question. Few
      studies, however, have considered that the problem might reside outside the
      device itself. OBJECTIVE: To investigate the correlation between left ear
      temperature and right ear temperature using an infrared tympanic thermometer
      (ITT). DESIGN: A prospective, single-blind trail with randomized assignment of
      the first ear to be assessed. SETTING/LOCATION: Welsh Institute of Chiropractic
      (WIOC), University of Glamorgan. SUBJECTS: One hundred and thirty two (132)
      asymptomatic subjects who were opportunistically sampled on entry into the WIOC.
      None of the subjects had any neurologic deficit, or any known underlying
      pathologic problems. All were students at the University of Glamorgan (age range,
      18-48 years). A smaller sample of the same cohort was used on a separate occasion
      to compare ITTs from 2 different manufacturers using the same protocol.
      INTERVENTION: Measurement of ear (ear canal/tympanic) temperature bilaterally
      using an ITT. OUTCOME MEASURES: Bilateral asymmetry in ear canal temperature.
      Analysis consisted of nonparametric statistical tests, using Spearman's
      correlation for comparison and the Wilcoxon matched pairs test for differences.
      RESULTS: In 132 subjects who completed the main study, although a degree of
      correlation was found, the relationship did not extrapolate through zero. At
      temperatures more than 0.4 degrees C above or below 36.7 degrees C, there was a
      significant difference in temperature in the left compared with the right ear.
      Additionally, the left ear tended to register a lower temperature than the right
      ear at temperatures below 36.7 degrees C, whereas the left ear tended to read a
      higher temperature than the right ear above 36.7 degrees C. CONCLUSIONS: The
      authors suggest that clinicians consider measuring both ears, and take the
      greater of the readings to be a more accurate reflection of the patient's core
      temperature. The difference may perhaps even be related to the person's health.
      This change in methodology should increase the reliability of the measurement and
      go some way toward restoring confidence in the use of ITT devices.

PMID- 15992233
TI  - Practice styles of beginner practitioners.
AB  - OBJECTIVES: In view of anecdotal evidence that points to variations in the ways
      that contemporary clinicians practice Chinese Medicine (CM), a study was
      undertaken to explore, identify, and analyze the styles of practice amongst a
      group of beginner acupuncturists in Australia. All participants in the study had
      been trained in the practice of Chinese Medicine rather than biomedicine. DESIGN
      AND METHODS: The study used a phenomenographic method to identify and map the
      group conceptions of practice from the extensive interview data. Differences
      between practice conceptions were identified in terms of the aim of the
      therapeutic encounter and the strategies used to achieve the aim. Practitioner
      client roles and the characteristics of the clinical encounter were also noted
      and analyzed with respect to varying practice conceptions. RESULTS AND
      CONCLUSIONS: Five major conceptions of practice were identified and discussed
      with respect to levels of complexity. It was argued that the more holistic and
      client-centered conceptions were better suited to contemporary practice in the
      West and were more beneficial in enabling practitioners to adapt culture-bound
      knowledge to contemporary health needs. This paper presents the major conclusions
      and theoretical perspectives that arose from the study rather than qualitative
      samples from the interview transcripts.

PMID- 15992234
TI  - A pilot study to examine a combination botanical for the treatment of menopausal
      symptoms.
AB  - OBJECTIVE: Hormone replacement therapy has become a controversial treatment for
      symptoms of menopause, leading many women and their physicians to search for
      safer, effective alternatives. Certain botanicals are known to contain
      phytoestrogenic activity, which may be helpful in alleviating menopausal
      symptoms. We report the results of a study using a combination botanical
      supplement to treat menopausal symptoms. DESIGN: Prospective pilot study.
      SETTING/LOCATION: Family practice medical center, Phoenix metropolitan area.
      SUBJECTS: Eight (8) women with moderate vasomotor and somatic symptoms of
      menopause. INTERVENTION: Combination botanicals daily for 3 months. OUTCOME
      MEASURES: Modified Kupperman Index (KI), daily hot flashes severity, and overall
      quality of life (QoL) using the SF-36 index, which were collected at enrollment,
      during treatment, and at the end of treatment. RESULTS: Mean KI total symptoms
      decreased from 30.3 +/- 7.5 to 22.9 +/- 8.4 (95% CI, 25-34), p = 0.0028. Daily
      hot flashes decreased from 68.1 +/- 14.3 to 39.6 +/- 9.7 (95% CI, 38-46), p =
      0.0003, and the overall QoL also improved at the end of treatment. CONCLUSIONS:
      This pilot study demonstrates the potential benefit of a combination botanical
      for improving moderate menopausal symptoms in women. The efficacy and role of
      combination botanicals for long-term use to reduce menopausal symptoms requires
      further exploration.

PMID- 15992235
TI  - Aromatherapy for outpatients with menopausal symptoms in obstetrics and
      gynecology.
AB  - OBJECTIVE: To introduce Complementary and Alternative Medicine (CAM) into a
      hospital department of obstetrics and gynecology with the goal of achieving
      integrative medicine, the authors investigated the effectiveness of aromatherapy
      for outpatients with menopausal symptoms. LOCATION: The department of obstetrics
      and gynecology, St. Marianna University Hospital, Kawasaki, Japan. DESIGN:
      Participants in the aromatherapy trial received a 30 minute aromatherapy session
      performed by an aromatherapist that included a consultation, massage, and home
      care guidance. After they carried out approximately 1 month of home care, they
      received a second aromatherapy session. The patients' physical and mental health
      status was measured at the start and endpoint of the trial by use of the
      Kupperman index (KI), the self-rating depression scale, and consultation.
      SUBJECTS: Fifteen (15) outpatients (mean age, 54.3 +/- 7.4 years) with menopausal
      symptoms in the department of obstetrics and gynecology of St. Marianna
      University Hospital. RESULTS: The mean value of the KI score was significantly
      lowered after the aromatherapy trial from 31.4 +/- 6.8 to 22.9 +/- 6.1 (p =
      0.001). CONCLUSION: This investigation shows that aromatherapy could be effective
      as a CAM method for menopausal symptoms in the setting of a hospital obstetrics
      and gynecology department.

PMID- 15992236
TI  - A critical review of randomized controlled trials of static magnets for pain
      relief.
AB  - OBJECTIVE: The aim of this review was to establish whether there is evidence for
      or against the efficacy of static magnets to produce analgesia. METHODS: A
      systematic literature review was undertaken of studies that compared the use of
      static magnets with an appropriate control for the treatment of pain. Study
      methods, their quality, and outcome were also reviewed. RESULTS: Overall, 13 of
      the 21 studies reported a significant analgesic effect due to static magnets. Of
      the 18 better quality studies with 3 points or more on the quality assessment, 11
      were positive and six were negative, and in one there was a non-significant trend
      towards a positive analgesic effect. In two of the negative studies, there are
      concerns over adequacy of magnet power for the type of pain, and in the other
      study of duration of exposure to the magnetic field. If these two studies are
      excluded on the grounds of inadequate treatment, then 11 out of 15 (73.3%) of the
      better quality studies demonstrated a positive effect of static magnets in
      achieving analgesia across a broad range of different types of pain (neuropathic,
      inflammatory, musculoskeletal, fibromyalgic, rheumatic, and postsurgical).
      CONCLUSIONS: The weight of evidence from published, well-conducted controlled
      trials suggests that static magnetic fields are able to induce analgesia.

PMID- 15992237
TI  - Comparison of healing of incised abscess wounds with honey and EUSOL dressing.
AB  - OBJECTIVE: To clinically compare the healing of abscess wounds dressed with
      either crude undiluted honey or Edinburgh University solution of lime (EUSOL).
      DESIGN: A prospective clinical randomized study. LOCATION: The Isolation
      Children's Ward of the Wesley Guild Hospital, Ilesa, an affiliate of the Obafemi
      Awolowo University, Ile-Ife, Nigeria. SUBJECTS: Thirty-two (32) Nigerian children
      with 43 pyomyositis abcesses. INTERVENTIONS: All subjects had fresh surgical
      incision and drainage of the abcesses and a 21-day course of ampicillin plus
      cloxacillin (Ampiclox) and gentamicin; the wounds were left to close
      spontaneously with twice-daily wound dressing with packing of the abscess cavity
      with either honey- or EUSOL-soaked gauze in two randomized treatment groups.
      OUTCOME MEASURES: The clinical conditions of the wound sites were documented on
      days 1, 3, 7, and 21 as either clean or dirty, dry or wet, granulation tissue
      present or absent, and epithelialization present or absent; the length of
      hospital stay was also measured. RESULTS: Honey-treated wounds demonstrated
      quicker healing and the length of hospital stay was significantly shorter in
      patients with honey-treated wounds than those treated with EUSOL (t = 2.45, p =
      0.019). CONCLUSIONS: Honey is a superior wound dressing agent to EUSOL. Honey is
      recommended for the dressing of infected wounds, more so in tropical countries,
      where it is most readily available.

PMID- 15992238
TI  - Can iridology detect susceptibility to cancer? A prospective case-controlled
      study.
AB  - OBJECTIVE: This prospective case-control study aimed to investigate the value of
      iridology as a diagnostic tool in detecting some common cancers. SUBJECTS: One
      hundred ten (110) subjects were enrolled in the study: 68 subjects had
      histologically proven cancers of the breast, ovary, uterus, prostate, or
      colorectum, and 42 were control subjects. METHODS: All subjects were examined by
      an experienced practitioner of iridology, who was unaware of their gender or
      medical details. He was allowed to suggest up to five diagnoses for each subject
      and his results were then compared with each subject's medical diagnosis to
      determine the accuracy of iridology in detecting malignancy. RESULTS: Iridology
      identified the correct diagnosis in only 3 cases (sensitivity, 0.04). CONCLUSION:
      Iridology was of no value in diagnosing the cancers investigated in this study.

PMID- 15992239
TI  - Medicinal benefits of green tea: Part I. Review of noncancer health benefits.
AB  - Tea, in the form of green or black tea, is one of the most widely consumed
      beverages in the world. Extracts of tea leaves also are sold as dietary
      supplements. However, with the increasing interest in the health properties of
      tea and a significant rise in scientific investigation, this review covers recent
      findings on the medicinal properties and noncancer health benefits of both green
      and black tea. In Part II, a review of anticancer properties of green tea
      extracts is presented. Green tea contains a unique set of catechins that possess
      biological activity in antioxidant, anti-angiogenesis, and antiproliferative
      assays potentially relevant to the prevention and treatment of various forms of
      cancer. Although there has been much focus on the biological properties of the
      major tea catechin epigallocatechin gallate (EGCg) and its antitumor properties,
      tea offers other health benefits; some due to the presence of other important
      constituents. Characteristics unrelated to the antioxidant properties of green
      and black teas may be responsible for tea's anticancer activity and improvement
      in cardiac health and atherosclerosis. Theanine in green tea may play a role in
      reducing stress. Oxidized catechins (theaflavins in black tea) may reduce
      cholesterol levels in blood. Synergistic properties of green tea extracts with
      other sources of polyphenolic constituents are increasingly recognized as being
      potentially important to the medicinal benefits of black and green teas.
      Furthermore, due to presumed antioxidant and antiaging properties, tea is now
      finding its way into topical preparations. Each of these aspects is surveyed.

PMID- 15992240
TI  - Patients' choice of asthma and allergy treatments.
AB  - BACKGROUND AND OBJECTIVES: Only a few studies have focused on a comparison
      between general practitioner (GP) patients' and classical homeopath (CH)
      patients' reasons for choosing, continuing or termination of their treatment by
      GPs or CHs, respectively. The existing studies are mostly based on quantitative
      methods and dealing with patients' reasons for choosing complementary and
      alternative medicine (CAM). The objective of this paper is to develop concepts to
      understand and compare Danish GP patients' and CH patients' initial choice of,
      continuing choice of, and termination of treatments for asthma and allergy.
      DESIGN: Data originate from an explorative study based on semistructured
      interviews with 18 GP patients and CH patients having asthma and allergy. The
      selection of the patients to the interviews was based on a questionnaire study
      including 88 respondents (response rate 58 patients). RESULTS: In understanding
      the patients' initial choice and continuing choice of treatment and termination
      of treatment, the concepts push-from, pull, press-into, stop, and stay factors
      are used. These factors are connected to the patients' experiences with
      conventional treatment, patients' attitudes toward and personal experiences with
      alternative treatment, and the patients' understanding of their asthma and
      allergy. The results of the study indicate that patients before seeking CHs had
      experienced inappropriate health care within the conventional health care system.
      The results of the study also indicate that if the CH patients experience
      inappropriate health care within homeopathic treatment, they terminate the
      treatment. CONCLUSIONS: The study indicates the importance of health providers'
      insight into GP patients' and CH patients' different reflections on adverse
      events, the patients' different understandings of asthma and allergy, and the
      different learning processes that GP patients and CH patients might be involved
      in while living with asthma and allergy. These are important issues for
      understanding patients' initial and, continuing choice of and termination of GP
      treatment and CH treatment, respectively.

PMID- 15992241
TI  - Convulsive syncope: an unusual complication of acupuncture treatment in older
      patients.
AB  - Vasovagal syncope is an uncommon complication during acupuncture. However,
      convulsive syncope during acupuncture treatment in older individuals is seldom
      reported in the literature. Two older patients who experienced convulsive syncope
      during acupuncture treatment at Taipei Veterans Hospital, Taipei, Taiwan, from
      January 2000 to December 2002 are reported. These cases are instructive to
      acupuncturists. Although acupuncture treatment is generally safe in most
      situations, one needs to be cautious in delivering acupuncture to older and
      debilitated individuals.

PMID- 15992242
TI  - Intravesical ozone therapy for progressive radiation-induced hematuria.
AB  - BACKGROUND: Progressive radiation-induced cystitis can become a serious clinical
      problem the therapeutic solution of which is limited and almost invariably
      aggressive. Ozone therapy is a nonconventional therapy that has been reported to
      offer benefits in late-onset wound healing and ischemic disorders. This report
      describes a patient with progressive radiation-induced hematuria from standard
      conservative treatment that was further treated with ozone therapy. METHOD: Ozone
      therapy was achieved by intravesical instillation of ozonized bi-distilled water
      over a period of 30 minutes, three sessions per week during the first weeks.
      Later, ozone therapy sessions were decreased and involved ozonized water or
      direct intravesicular instillation of ozone at 20-25 microg/mL. RESULTS:
      Hematuria was successfully controlled by intravesical application of ozone
      therapy. CONCLUSIONS: The successes achieved with this technique suggest that
      intravesicular instillation of ozonized bi-distilled water or ozone merits
      further investigation with a view to its application to counter this radiation
      induced side-effect.

PMID- 15992243
TI  - Improvement of postoperative analgesia during cancer surgery with Limoge's
      current: a personal experience.
AB  - BACKGROUND: The anesthesiologist took advantage of a personal experience to
      determine whether transcutaneous cranial electrical stimulation using Limoge's
      current (TCES-LC) improved the level of postoperative analgesia by potentiating
      anesthetic agents used during the intra- and postoperative phases. Included were
      analgesics injected through an epidural thoracic catheter (T8-T9) positioned at
      the end of an esophagectomy. Another reason for a self-experimentation was to be
      able to evaluate the psycholeptic effects of TCES-LC to gain a better
      understanding of the problems linked with pain during treatment. METHODS: The
      Limoge' current is bidirectional and consists of a high-frequency biphasic
      asymmetrical wave composed of modulated, high-frequency (166-kHz) pulse trains
      with a repetition cycle of 100 Hz. TCES-LC was initiated 2 hours before
      anesthetic induction without any tranquilizer or other medication. TCES-LC was
      continuously applied during the entire surgical procedure and continued 48 hours
      postoperatively in the intensive care unit (ICU). As the objective was not to
      obtain electrical anesthesia, the usual anesthetic protocol was used during
      surgery. RESULTS: During the initial 48 postoperative hours with continuous
      application of TCES-LC (D0-D1), a decrease of the epidural anesthetic dose
      requirement was observed for ropivacaine, and sufentanil (-25% and -60%
      respectively). A similar decrease in these medications was also measured on day 2
      (D2), while TCESLC was terminated. This decrease was amplified day 3 (D3) for
      both ropivacaine and sufentanil (-50% and -73% respectively). On day 4 (D4) the
      epidural anesthetics were totally suppressed (1 day before the normal
      conventional schedule planned for by the ICU physician with this type surgery).
      CONCLUSION: Future clinical trials need to be conducted to show the significant
      advantages of TCES-LC in alternative and complementary medicine.

PMID- 15992244
TI  - Generalized entanglement: a new theoretical model for understanding the effects
      of complementary and alternative medicine.
AB  - BACKGROUND AND PROBLEM: A main problem for the acceptance of many methods
      belonging to the broad spectrum of complementary and alternative medicine (CAM)
      is that there is no conceivable theoretical bridge between the mainstream
      biomedical model and CAM theories and practice. Although empirical evidence is
      one important side of the coin of credibility, theoretical feasibility is the
      other. History of science teaches that no amount of empirical evidence will
      convince sceptics and followers of more conventional paradigms as long as there
      is no good theoretical model to make empirical findings plausible. METHODS AND
      SOLUTION: I therefore propose to broaden the spectrum of theoretical concepts
      beyond the reigning local-causalist model toward a non-local model that
      encompasses effects as encountered in CAM. Such a model can be derived from a
      generalized and weaker version of quantum theory recently developed and published
      by my colleagues and I as weak quantum theory (WQT). This theoretical model
      predicts nonlocal correlations analogous to Einstein-Podolsky-Rosen (EPR)-like
      correlations in quantum mechanics proper. The discerning moment, though, is that
      these nonlocal correlations within WQT are not EPR correlations postulated to
      extend into the classical world, but a broader, generalized version of
      entanglement not dependent on the strict quantum nature of the system under
      question. WQT predicts entanglement between elements of a system if two variables
      or observables are complementary: one describing a global and one the local
      aspects of the system. Entanglement then ensues between those local elements of a
      system that are complementary to the global description or observable of that
      system. DISCUSSION AND CONCLUSIONS: This paper explores this rather abstract and
      general notion and expands it into more concrete examples. It is at the moment a
      purely explanatory structure, which, however, lends itself to exact empirical
      testing due to rather precise predictions, which will be developed. Because this
      structure of generalized entanglement is ubiquitous and also operative in
      conventional medicine, and because it is derived from one of the strongest
      theories that science has developed so far, it would constitute a theoretical
      bridge between the different medical and scientific traditions.

PMID- 15992245
TI  - Influence of worldview on health care choices among persons with chronic pain.
AB  - OBJECTIVE: The aim of this research was to examine relationships between the
      Pepperian worldviews of people with chronic pain and the health care choices that
      they make. DESIGN: A convenience sample survey was done. SETTING: University
      Medical Center Pain Clinic, Tucson, Arizona. SUBJECTS: Men and women patients (n
      = 96) with nonmalignant chronic pain. OUTCOME MEASURES: World Hypothesis Scale;
      Health Care Choice List. RESULTS: Findings indicate that the combination of age
      and formistic worldview are statistically significant predictors of conventional
      health care choices by participants in this study. Older patients and persons
      with a predominantly formistic worldview were less likely to use complementary
      and alternative medicine (CAM) as a choice among this sample with chronic
      nonmalignant pain. Borderline significant associations were noted between persons
      with formistic or mechanistic worldviews and conventional health care choices,
      and persons with contextualistic, organismic, or equal scores in two worldview
      categories and CAM health care choices. Although rates of CAM use did not
      significantly differ from conventional choices, the prevalence rate for CAM use
      was high (55.2%) based on national findings. CONCLUSIONS: Results of this study
      provide a link to understanding how underlying philosophies can contribute to the
      reasons people with chronic pain make health care decisions. Further exploration
      of worldviews might very well contribute to best practices for consumer health
      care by engaging in communication styles and belief systems consistent with
      consumers' personal schemas.

PMID- 15992246
TI  - Integrating complementary therapies into community mental health practice: an
      exploration.
AB  - OBJECTIVES: To (1) describe the integration of massage and energy-based therapies
      with psychotherapy in a community mental health center, (2) to present
      qualitative feedback on the service, and (3) to present pilot data from a sample
      of long-term clients with persistent mental health concerns. DESIGN: A
      noncontrolled pilot study was conducted using interview data before and self
      report instruments after completing a brief program of complementary therapy
      accompanying ongoing psychotherapy. SETTINGS/LOCATION: The program took place at
      a comprehensive community mental health center in southern Maine and in the
      private offices of massage therapists and energy healing practitioners who
      contracted with the program. SUBJECTS: Subjects were 20 women and 5 men, with
      mean age of 42 years and a mean history of 7.4 years of mental health treatment.
      All had histories that included trauma, 10 of which involved sexual abuse. The
      Diagnostic and Statistical Manual of Mental Disorders IV Axis I diagnoses were
      PTSD (10), major depression (nine), anxiety disorder (three), and dual diagnosis
      (three). INTERVENTIONS: Clients receiving ongoing psychotherapy were assigned to
      one modality of complementary therapy based on clinical judgment, availability of
      practitioners, and client interest. Modalities used were massage, acupuncture,
      Reiki, and Healing Touch. The mean number of sessions was five. OUTCOME MEASURES:
      Clients completed an investigator-generated instrument with Likert-scaled ratings
      of satisfaction and perceived changes in four dimensions of trauma recovery:
      perceived interpersonal safety, interpersonal boundary setting, bodily sensation,
      and bodily shame. RESULTS: Clients reported high levels of satisfaction with the
      service and significant levels of perceived (self-rated) change on each outcome
      measure. Qualitative results included enhanced psychotherapeutic outcomes
      reported by mental health clinicians. CONCLUSIONS: The integration of
      complementary therapies into community mental health practice may hold promise of
      enhancing mental health outcomes and improving quality of life for long-term
      users of mental health services.

PMID- 15992251
TI  - Response inhibition and attention deficit hyperactivity disorder with and without
      oppositional defiant disorder screened from a community sample.
AB  - The study compared performance of children with high levels of attention deficit
      hyperactivity disorder (ADHD; n=22), children with ADHD and oppositional defiant
      disorder (ODD; n=19), and a control group (n=20) on a Go-No-go test in a self
      paced and computer-paced condition. Each condition, in turn, was run in a reward
      and a nonreward condition. The children were recruited through screening of a
      school population without ADHD or ODD (N=450). Findings indicated that children
      having high levels of ADHD plus ODD showed poor impulse control in all 4
      conditions. No poor impulse control was found in the group with high levels of
      ADHD. This group demonstrated slower RTs across the computer-paced conditions.
      Findings were discussed in terms of the response-inhibition hypothesis, as
      formulated by Barkley (1997), the delay-aversion theory (Sonuga-Barke, 1995), and
      the state-regulation theory (Van der Meere, 2002).

PMID- 15992252
TI  - Cognitive performance differentiates selected aspects of psychosocial maturity in
      adolescence.
AB  - This study examined relations between adolescents' cognitive performance and
      psychosocial maturity. Forty-eight adolescents in Grades 9 and 12 were measured
      on intelligence (composite, crystallized, fluid), executive functioning (backward
      digit span, Color Trails 2 (CT2), Stroop, everyday problem solving), and
      psychosocial maturity (subjective age, problem behavior, psychological maturity).
      Significant relations between aspects of cognitive performance and psychosocial
      maturity emerged. Problem behavior was related to lower crystallized
      intelligence, whereas psychological maturity was related to higher crystallized
      intelligence and better performance on the CT2. Psychosocially mature adolescents
      had significantly higher composite IQ scores than did pseudomature adolescents.
      Mature adolescents also showed advantages in crystallized and fluid intelligence,
      and in performance on the CT2, compared to their less mature counterparts (the
      combined group of immature and pseudomature adolescents). The results suggest
      that cognitive abilities are related to psychosocial maturity.

PMID- 15992253
TI  - Gender differences in relations of mental rotation, verbal fluency, and SAT
      scores to finger length ratios as hormonal indexes.
AB  - One hundred thirty-four university students (93 women, 41 men) were administered
      the Vandenberg Mental Rotation Test and the Thurstone Word Fluency Test, and they
      were asked to report their Scholastic Achievement Test scores. Finger lengths
      were measured, because literature has reported gender differences in the ratio of
      the 2nd to 4th, 2nd to 3rd, and 2nd to 5th finger lengths, such that the ratio is
      larger in women than in men. The goal of this study was to evaluate the relations
      between finger-length ratios and cognitive skills, such as spatial skills and
      verbal fluency, which have shown gender differences and direct relations to
      hormonal effects. Gender differences were found in the expected directions, such
      that the men performed better than the women for mental rotation, the women
      performed better than the men for verbal fluency, and the finger-length ratios
      were in the directions reported in the literature. The finger-length ratios
      showed an interesting relation with the cognitive variables for the men and
      women. For the men, better performance on the measures, including mental
      rotation, verbal fluency, and verbal Scholastic Achievement Test score was
      associated with less of a male-typical finger-length ratio pattern, or higher
      ratios. For the women, better performance for mental rotation and verbal fluency
      was associated with less of a female-typical finger-length ratio pattern, or
      lower ratios. Thus, in this group of college students, better cognitive
      performance was associated with a less gender-typical finger-length ratio, for
      both men and women. These findings are discussed in the context of other similar
      reports and a possible curvilinear relation between hormones and cognition in
      normal populations.

PMID- 15992255
TI  - The influence of the parents' educational level on the development of executive
      functions.
AB  - Information about the influence of educational variables on the development of
      executive functions is limited. The aim of this study was to analyze the relation
      of the parents' educational level and the type of school the child attended
      (private or public school) to children's executive functioning test performance.
      Six hundred twenty-two participants, ages 5 to 14 years (276 boys, 346 girls)
      were selected from Colombia and Mexico and grouped according to three variables:
      age (5-6, 7-8, 9-10, 11-12, and 13-14 years), gender (boys and girls), and school
      type (private and public). Eight executive functioning tests taken from the
      Evaluacion Neuropsicologica Infantil; Matute, Rosselli, Ardila, & Ostrosky, (in
      press) were individually administered: Semantic Verbal Fluency, Phonemic Verbal
      Fluency, Semantic Graphic Fluency, Nonsemantic Graphic Fluency, Matrices,
      Similarities, Card Sorting, and the Mexican Pyramid. There was a significant
      effect of age on all the test scores and a significant effect of type of school
      attended on all but Semantic Verbal Fluency and Nonsemantic Graphic Fluency
      tests. Most children's test scores, particularly verbal test scores,
      significantly correlated with parents' educational level. Our results suggest
      that the differences in test scores between the public and private school
      children depended on some conditions existing outside the school, such as the
      parents' level of education. Implications of these findings for the understanding
      of the influence of environmental factors on the development of executive
      functions are presented.

PMID- 15992254
TI  - Sustained attention in mild Alzheimer's disease.
AB  - The vigilance decrement in perceptual sensitivity was examined in 10 patients
      with mild Alzheimer's disease (AD) and 20 age-matched controls. A visual high
      event rate digit-discrimination task lasting 7.2 min. (six 1.2 min blocks) was
      presented at different levels of stimulus degradation. Previous studies have
      shown that sensitivity decrements (d') over time at high-stimulus degradation
      result from demands on effortful processing. For all degradation levels, the
      overall level of vigilance (d') was lower in AD patients than in controls. All
      participants showed sensitivity decrement over blocks, with greater decrement at
      higher degradation levels. AD patients exhibited greater sensitivity decrement
      over time at the highest degradation level they all could perform relative to
      control participants. There were no concomitant changes in either response bias
      (C) or response times. The results indicate that mild AD patients have overall
      lower levels of vigilance under conditions that require both automatic and
      effortful processing. Mild AD patients also exhibit a deficit in the maintenance
      of vigilance over time under effortful processing conditions. Although the sample
      of AD patients was small, results further suggest that both possible and probable
      AD patients had greater sensitivity decrement over time at the highest
      degradation level than did control participants, but only probable AD patients
      had lower overall levels of vigilance. In the possible AD patients as a group,
      the decrement in vigilance occurred in the absence of concurrent deficits on
      standard attentional tasks, such as the Stroop and Trail Making tests, suggesting
      that deficits in vigilance over time may appear earlier than deficits in
      selective attention.

PMID- 15992257
TI  - Application of the genome sequence to address concerns that Mycobacterium avium
      subspecies paratuberculosis might be a foodborne pathogen.
AB  - Johne's disease, a chronic inflammatory disease caused by infection with
      Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis), is one of
      the most prevalent and costly diseases of dairy cattle worldwide. This ruminant
      pathogen is closely related to the ubiquitous animal and human pathogen
      Mycobacterium avium subspecies avium (M. avium), confounding the development of
      specific diagnostic reagents. Exacerbating this problem further is that most
      existing microbiological, serological, and immunologic assays for the
      identification of infected animals are inadequate. This is primarily because of
      the slow-growing nature of the organism, genetic intractability and the previous
      lack of information on M. paratuberculosis subspecies-specific genes or proteins
      that may enable the development of specific and sensitive assays. New detection
      tools are critically needed to definitively answer questions surrounding M.
      paratuberculosis as a foodborne pathogen as well as aid in determining if it is a
      contributing factor in Crohn's disease. Thus, the recent characterization of the
      complete genome sequence of M. paratuberculosis in our laboratories has been a
      major step forward in meeting this need. We have performed studies that utilize
      genomic information for the identification of specific DNA sequences and protein
      antigens in M. paratuberculosis. Based on a preliminary in silico comparison of
      the M. paratuberculosis genome sequence with that of M. avium, we have now
      identified at least 35 novel coding sequences that are unique to M.
      paratuberculosis. These in silico data were then confirmed and expanded by PCR
      amplification analysis with DNA from several species and isolates of
      mycobacteria. Finally, these unique sequences have been incorporated into an
      antigen discovery project that may allow reliable detection of the bacterium in
      antigen-based diagnostic tests. Application of these new tools in addressing
      foodborne related issues of M. paratuberculosis is discussed.

PMID- 15992258
TI  - Evaluation of IS900-PCR assay for detection of Mycobacterium avium subspecies
      Paratuberculosis infection in cattle using quarter milk and bulk tank milk
      samples.
AB  - A study was conducted to evaluate sensitivity, specificity, and predictive value
      of IS900-PCR assay for detection of Mycobacterium avium subspecies
      paratuberculosis in pooled quarter milk and bulk tank milk. Feces, blood and
      pooled quarter milk from 1493 lactating cattle on 29 herds were analyzed. Bulk
      tank milk (n = 29 bulk tanks) samples were also examined. Culture analysis
      revealed that 10.9%, 2.8%, and 20.6% of fecal, pooled quarter milk samples and
      bulk tanks were positive for M. avium subsp. paratuberculosis, respectively.
      While 13.5% and 27.5% of pooled quarter milk samples and bulk tanks were positive
      by IS900 PCR assay, respectively. Moderate to high antibody titers for M. avium
      subsp. paratuberculosis were detected in 223 of 1493 (14.4%) cows. Cows positive
      on fecal culture were taken as true positives relative to which the IS900 PCR
      assay was evaluated. The sensitivity and predictive value of KELA, pooled quarter
      milk culture, and IS900 PCR assay increased with lactation age. While the
      specificity of the tests decreased with increase in lactation age. Overall, the
      IS900 PCR assay using pooled quarter milk samples had a sensitivity, specificity
      and predictive value of 0.87, 0.95 and 0.71, respectively. The IS900 PCR assay
      using bulk tank milk had poor sensitivity (0.21), specificity (0.5) and
      predictive value (0.6). Pooled quarter milk culture analysis had a very low
      sensitivity (0.17). The kinetics ELISA had lower sensitivity (0.59), specificity
      (0.90) and predictive value (0.43) as compared to the IS900 PCR assay using
      pooled quarter milk samples. Results from our study suggest that IS900 PCR assay
      using bulk tank milk may not be useful for screening herds with M. avium subsp.
      paratuberculosis infected animals. In conclusion, use of IS900 PCR assay for cows
      in 2(nd) lactation and higher, using aseptically collected pooled quarter milk
      samples, can be a useful tool for screening and monitoring lactating cattle in
      herds with M. avium subsp. paratuberculosis infection.

PMID- 15992259
TI  - Persistence of Salmonella enterica serovar typhimurium on lettuce and parsley and
      in soils on which they were grown in fields treated with contaminated manure
      composts or irrigation water.
AB  - There are many sources of pathogen contamination of vegetable crops in the field
      that include manure used as fertilizer and irrigation water. An avirulent strain
      of Salmonella enterica serovar Typhimurium was added to three different types of
      composts-PM-5 (poultry manure compost), 338 (dairy manure compost), and NVIRO-4
      (alkaline stabilized dairy manure compost)-and irrigation water at 10(7) colony
      forming units (cfu)/g and 10(5) cfu/mL, respectively, to determine under field
      conditions the persistence of salmonellae in soils treated with these composts or
      irrigation water, and also on leaf lettuce and parsley grown on such treated
      soil. Contaminated compost was applied to soil in the field as a strip at a rate
      of 4.5 metric tons/hectare on the day before lettuce and parsley seedlings were
      transplanted. Contaminated irrigation water was applied only once on the plants
      at the rate of 2 liters per plot on the same day after the seedlings were
      transplanted. Twenty-five plots, each measuring 1.8 x 4.6 meters, were used for
      each crop, with five treatments (one without compost, three with each of the
      three composts, and one without compost but applied with contaminated water) and
      five replication plots for each treatment. Salmonella persisted for 161 and up to
      231 days in soils amended with contaminated composts on which lettuce and
      parsley, respectively, were grown, and was detected for up to 63 days and 231
      days on lettuce and parsley, respectively. The type of contaminated compost had
      minimal effect on the persistence of S. Typhimurium in soil. Occurrence of
      Salmonella on vegetables and survival in soil on which these vegetables were
      grown, irrespective of source of contamination through irrigation water or
      compost, were similar, suggesting both contaminated manure compost and irrigation
      water can play important roles in contaminating soil and vegetables with
      Salmonella for an extended period of time.

PMID- 15992260
TI  - Evaluation of universal pre-enrichment broth for isolation of Salmonella spp.,
      Escherichia coli O157:H7, and Listeria monocytogenes from dairy farm
      environmental samples.
AB  - Use of universal pre-enrichment broth (UPB) as a primary enrichment medium for
      detection of Salmonella spp., Escherichia coli O157:H7, and Listeria
      monocytogenes from dairy farm environmental samples was evaluated. There were no
      differences in bacterial growth between UPB and selective primary enrichment
      broths for each pathogen inoculated individually or in combination at 10(1) and
      10(2) colony forming units/mL. In addition, no differences were observed when UPB
      and selective primary enrichment broths were compared for detection efficiency of
      pathogens in artificially contaminated raw milk and fecal samples. Listeria
      enrichment broth (LEB) was compared with UPB to support growth of L.
      monocytogenes from naturally contaminated environmental samples. Listeria
      monocytogenes was isolated from seven of 30 samples enriched in UPB and six of 30
      samples enriched in LEB. Dairy farm environmental samples were examined for
      recovery of the three pathogens using UPB. Subsequent isolation was achieved
      using selective secondary enrichment of each pathogen. Listeria monocytogenes,
      Salmonella spp., and E. coli O157:H7 were isolated in 13.4% (30 of 224), 8.9% (20
      of 224), and 2.2% (five of 224) of samples, respectively. Isolation rates of the
      three pathogens were somewhat higher than in previous reports. Overall, UPB
      supported growth of test pathogens to detectable levels within 24 h. Our results
      demonstrate that UPB has potential for routine use in isolation of foodborne
      pathogens from diverse environmental samples.

PMID- 15992261
TI  - Low prevalence of yadA-positive Yersinia enterocolitica in sows.
AB  - Yersinia enterocolitica 4/O:3 is commonly isolated from fattening pigs in
      Finland, but its prevalence in sows is relatively unknown. The current study
      determined the prevalence of yadA-positive Y. enterocolitica in sows and
      fattening pigs with polymerase chain reaction (PCR) and culture methods. The
      strains were characterized with pulsed-field gel electrophoresis (PFGE) using
      NotI DNA-restriction enzyme. Pathogenic Y. enterocolitica was detected in only
      14% of sow tonsils compared with 56% of tonsils of fattening pigs. The prevalence
      varied between seven slaughterhouses from 0% to 30% in sows and from 30% to 87%
      in fattening pigs. A total of 37 NotI profiles were obtained from 148 Y.
      enterocolitica 4/O:3 strains isolated from 134 tonsil samples: eight profiles
      were obtained from 26 sow strains and 34 from 122 fattening pig strains. Two
      types predominated in both sows and fattening pigs. The prevalence of yadA
      positive Y. enterocolitica in fattening pigs increased from 1995 versus 1999; the
      mean prevalence in five slaughterhouses for the 2 years was 33% and 64%,
      respectively. Seven NotI profiles, including the two common types, were found
      both years. In conclusion, pathogenic Y. enterocolitica was detected at a
      significantly lower rate in sows than in fattening pigs. Moreover, the prevalence
      of this pathogen in fattening pigs was significantly higher in 1999 than in 1995.
      Some Y. enterocolitica 4/O:3 strains persisting among slaughter swine were
      demonstrated to be very stable genetically. This study shows that fattening pigs
      are an important reservoir of different genotypes of Y. enterocolitica 4/O:3
      strains.

PMID- 15992262
TI  - Proteolytic Clostridium botulinum type B in the gastric content of a patient with
      type E botulism due to whitefish eggs.
AB  - Whitefish eggs were confirmed by pulsed-field gel electrophoresis to cause type E
      foodborne botulism in a 54-year-old patient in Finland. Botulinum neurotoxin
      and/or nonproteolytic Clostridium botulinum type E organisms were detected in
      fecal and gastric samples from the patient and in suspected whitefish eggs. Apart
      from C. botulinum type E, proteolytic type B organisms were detected in the
      patient's gastric content. This was considered to be insignificant with respect
      to the clinical disease, suggesting botulinal spores to be occasionally present
      in the human gastrointestinal tract without any apparent clinical significance.
      This is the first domestic case of foodborne botulism in Finland.

PMID- 15992263
TI  - Effects of sodium chlorate on antibiotic resistance in Escherichia coli O157:H7.
AB  - The spread of antibiotic resistance from farm animals to human pathogens has
      become a matter of great public health significance, and methods to reduce
      foodborne pathogenic bacteria without utilizing traditional antibiotics have been
      sought. Chlorate kills Escherichia coli O157:H7 in vitro and in vivo and has been
      proposed as a feed additive to be included in food animal rations immediately
      prior to slaughter to reduce E. coli O157:H7 populations in the animal
      gastrointestinal tract. This study was designed to examine the effect that the
      development of chlorate resistance in E. coli O157:H7 has on resistance to 32
      medically important antibiotics. Chlorate resistance numerically increased
      antibiotic resistance in E. coli O157:H7 strain 6058 and strain 933 to six and
      four antibiotics, respectively, but chlorate resistance affected resistance to
      only two antibiotics (cefoxotin and sulfadimethoxine) in both strains examined.
      Based on the fact that chlorate resistant mutants do not appear to compete well
      in vivo and based on the results of the current study, it appears unlikely that
      chlorate treatment will result in a dissemination of antibiotic resistance.
      However, further research is needed to confirm these results.

PMID- 15992264
TI  - Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease.

PMID- 15992266
TI  - Epidemiology, pathogenesis, and prevention of foodborne Vibrio parahaemolyticus
      infections.
AB  - Since its discovery about 50 years ago, Vibrio parahaemolyticus has been
      implicated as a major cause of foodborne illness around the globe. V.
      parahaemolyticus is a natural inhabitant of marine waters. Human infections are
      most commonly associated with the consumption of raw, undercooked or contaminated
      shellfish. A few individual V. parahaemolyticus virulence factors, including the
      thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH), have been
      investigated in depth, yet a comprehensive understanding of this organism's
      ability to cause disease remains unclear. Since 1996, serotype O3:K6 strains have
      been associated with an increased incidence of gastroenteritis in India and in
      Southeast Asia, and with large-scale foodborne outbreaks in the United States
      (US). In light of the emerging status of pathogenic V. parahaemolyticus, the US
      Food and Drug Administration conducted a microbial risk assessment to
      characterize the risk of contracting V. parahaemolyticus infections from
      consuming raw oysters. This review summarizes epidemiological findings, discusses
      recognized and putative V. parahaemolyticus virulence factors and pathogenicity
      mechanisms, and describes strategies for preventing V. parahaemolyticus
      infections.

PMID- 15992267
TI  - Major foodborne illness causing viruses and current status of vaccines against
      the diseases.
AB  - Even though viruses, unlike bacteria, cannot grow in or on foods, foodborne
      illnesses are associated with viruses due to contamination of the fresh produce
      or processed food by virus-containing fecal material. The commonly reported major
      foodborne illnesses are due to Noroviruses, hepatitis A and E viruses,
      rotaviruses, and astroviruses. Among all illnesses caused by foodborne pathogens,
      recent estimates of as high as 67% have been attributed to viruses alone, and an
      upward trend in the of transmission of viruses by food and water has been
      recently acknowledged. Due to the highly infectious nature of these viruses and
      their survival under drastic conditions such as high acidic pH and low
      temperatures, it has long been recognized that immunization against such
      pathogens is the ideal solution to provide protection against the illness and
      disease outbreaks associated with these viruses. With an increased recognition of
      the clinical significance and impact of acute viral illness associated with food
      and water in humans of all ages, there has been a recent surge in developing
      prophylactic vaccines against such viruses. So far, except for hepatitis A virus,
      there are no vaccines available to prevent illness associated with foodborne
      viruses. Outbreaks of hepatitis A have been significantly reduced due to
      widespread immunization of some risk groups. It is clear from the literature that
      novel strategies currently in development may lead to vaccines against
      noroviruses and rotaviruses in the near future, offering hope that such vaccines
      will significantly reduce the burden associated with foodborne illnesses
      associated with these viruses.

PMID- 15992268
TI  - Detection of sorbitol-negative and sorbitol-positive Shiga toxin-producing
      Escherichia coli, Listeria monocytogenes, Campylobacter jejuni, and Salmonella
      spp. in dairy farm environmental samples.
AB  - Six visits were conducted to four dairy farms to collect swab, liquid, and solid
      dairy farm environmental samples (165 to 180/farm; 15 sample types). The
      objective of the study was to determine on-farm sources of Campylobacter jejuni,
      Salmonella spp., Listeria monocytogenes, and Shiga toxin-producing Escherichia
      coli (STEC), which might serve as reservoirs for transmission of pathogens.
      Samples were analyzed using mostly U.S. Food and Drug Administration's
      Bacteriological Analytical Manual protocols; however, Salmonella spp., L.
      monocytogenes and STEC were co-enriched in universal pre-enrichment broth.
      Campylobacter jejuni were enriched in Bolton broth containing Bolton broth
      supplement. Pathogens were isolated on agar media, typed biochemically, and
      confirmed using multiplex polymerase chain reaction protocols. Campylobacter
      jejuni, Salmonella spp., L. monocytogenes, Sorbitol-negative (SN)-STEC O157:H7,
      and sorbitol-positive (SP)-STEC, respectively, were isolated from 5.06%, 3.76%,
      6.51%, 0.72%, and 17.3% of samples evaluated. Whereas other pathogens were
      isolated from all four farms, SN-STEC O157:H7 were isolated from only two farms.
      Diverse serotypes of SP-STEC including O157:H7, O26:H11, O111, and O103 were
      isolated. None of the five pathogen groups studied were isolated from bulk tank
      milk (BTM). Most pathogens (44.2%) were isolated directly from fecal samples.
      Bovine fecal samples, lagoon water, bedding, bird droppings, and rat intestinal
      contents constituted areas of major concern on dairy farms. Although in-line milk
      filters from two farms tested positive for Salmonella or L. monocytogenes, none
      of the pathogens were detected in the corresponding BTM samples. Good manure
      management practices, including control of feral animals, are critical in
      assuring dairy farm hygiene. Identification of on-farm pathogen reservoirs could
      aid with implementation of farm-specific pathogen reduction programs.

PMID- 15992269
TI  - Overcoming RNA inhibition in the fluorescent polymerase chain reaction assay to
      enhance detection of bovine DNA in cattle feeds.
AB  - The practice of incorporating mammalian protein in ruminant feeds was banned in
      the United States in 1997 as a measure to avoid transmission of bovine spongiform
      encephalopathy (BSE). A sensitive means of identifying the banned additives in
      feeds would be by detection of species-specific DNA using the polymerase chain
      reaction (PCR). However, problems may arise in the PCR due to the presence of
      inhibitory substances. Using human DNA as an internal PCR control, inhibitory
      substances were evident in the DNA extraction products of cattle feeds. The
      results of heating experiments excluded enzymes as a cause of inhibition, and
      spectrophotometric calculations suggested the possibility of RNA contamination.
      Co-electrophoresis of untreated and RNAse digested extracts confirmed the
      presence of RNA in the undigested product. Seven cattle feeds were spiked with
      predetermined amounts of bovine meat and bone meal (BMBM). The DNA extracted
      products were treated with RNAse and the bovine specific mitochondrial DNA (B
      mtDNA) was amplified by PCR. The minimum level of detection of B-mtDNA was
      influenced by RNAse treatment and feed composition. RNAse treatment decreased
      false-negative results overall by 75%. False-negative results were decreased 100%
      in the higher BMBM concentrations and 50% in the lower BMBM concentrations. Also,
      each cattle feed was spiked to attain a 2% wt/wt concentration with each swine,
      fish, sheep, or poultry product, or cattle dried blood. Amplification of B-mtDNA
      occurred only with the cattle dried blood and only in three feeds in which B
      mtDNA was detected at the only level tested (2%). A commercial
      immunochromotographic assay (Neogen) detected the spiked BMBM in only one of the
      seven feeds and only at the upper concentration (1%).

PMID- 15992270
TI  - Examination of heat stress and stage of lactation (early versus late) on fecal
      shedding of E. coli O157:H7 and Salmonella in dairy cattle.
AB  - Mature, healthy lactating dairy cattle were sampled on two farms in the
      southwestern United States to examine the effects of heat stress (Experiment I)
      and stage of lactation (Experiment II) on the fecal shedding of E. coli O157:H7
      and Salmonella. To examine the effects of heat stress, fecal samples were
      collected from 45 cows at 7:00 AM (coolest part of the day) and 5:00 PM (hottest
      part of the day) in August 2002 on a 250 cow dairy. The study was replicated one
      month later (n = 170 total samples). A temperature-heat index (THI) was
      calculated for each sampling time. In Experiment II, stage of lactation was
      examined by sampling lactating dairy cattle early [< 60 days in milk (DIM)] and
      late (> 150 DIM) in the lactation cycle in the summer of 2001. The study was
      replicated the following summer (60 cows/group/replicate; n = 240 total samples).
      For Experiment I, THI averaged 75 and 82 for the AM and PM samplings,
      respectively, indicating the cows were beginning to experience heat stress in the
      morning and by afternoon were in severe heat stress. The shedding of E. coli
      O157:H7 tended to be higher (p = 0.09) in the afternoon sampling of the first
      replicate, however was not different in the second replicate or when both
      replicates were pooled (p > 0.10). Salmonella shedding was not different (p >
      0.10) at any sampling time with nearly 100% of the cows positive. Stage of
      lactation had no effect on the number of cows shedding E. coli O157:H7 (p >
      0.10). Salmonella shedding tended to be higher (p = 0.09) in early lactation cows
      in the first replicate, while in the second replicate more late lactation cows
      were shedding Salmonella (p < 0.05); however, there were no differences due to
      stage of lactation when replicates were pooled (p > 0.10). While further research
      is needed, results of this research highlight the variability in pathogen
      shedding in healthy dairy cattle and indicate that environmental factors and/or
      production demands may influence shedding patterns of E. coli O157:H7 and
      Salmonella.

PMID- 15992271
TI  - Emergence of pork carnitas as a cause of foodborne disease outbreaks in Chicago.
AB  - Carnitas are fried chunks of pork frequently served in Mexican-origin households,
      food service establishments, and social gatherings. During 1995-2002, carnitas
      emerged as the most frequently implicated vehicle of transmission in foodborne
      disease outbreaks in Chicago. Five (6%) of 90 foodborne disease outbreaks
      investigated and reported in Chicago during this period were linked to carnitas,
      and they accounted for 108 illnesses and 11 hospitalizations. The etiologic agent
      in four outbreaks was Salmonella, and these outbreaks accounted for 29% of the 14
      Salmonella-associated foodborne disease outbreaks in Chicago during this period.
      Unsafe food handling practices that occurred after cooking were identified as
      contributing to multiple carnitas-associated outbreaks. Local health departments
      that serve significant Mexican-origin populations should be aware of carnitas as
      a potential source of foodborne disease, particularly salmonellosis.

PMID- 15992272
TI  - Phenotypic and genetic markers for serotype-specific detection of Shiga toxin
      producing Escherichia coli O26 strains from North America.
AB  - Phenotypic and genetic markers of Shiga toxin-producing Escherichia coli (STEC)
      O26 from North America were used to develop serotype-specific protocols for
      detection of this pathogen. Carbohydrate fermentation profiles and prevalence of
      gene sequences associated with STEC O26 (n = 20) were examined. Non-STEC O26 (n =
      17), E. coli O157 (n = 20), E. coli O111 (n = 22), and generic E. coli (n = 21)
      were used as comparison strains. Effects of supplements: cefixime-tellurite, 4
      methylumbelliferyl-beta-D-glucuronide (MUG) and chromogenic additives (5-bromo4
      chloro-3-indolyl-beta-D-galactopyranoside (X-Gal), 5-bromo-4-chloro-3-indolyl
      beta-D-glucuronide (X-GlcA) and o-nitrophenyl-beta-D-galactopyranoside (ONPG),
      added to isolation agar media were examined. Tests for presence of gene sequences
      encoding beta intimin (eae beta), Shiga toxin 1 and 2 (stx1 and stx2), H7
      flagella (flicCh7), enterohemolysin (ehlyA), O26 somatic antigen (wzx), and high
      pathogenicity island genes (irp2 and fyuA) were conducted using multiplex
      polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) of XbaI
      restriction endonuclease genomic DNA digests was used to establish clonality
      among E. coli O26 strains. Of the 26 carbohydrates tested, only rhamnose had
      diagnostic value. Rhamnose non-fermenters included STEC O26 (100%), non-STEC O26
      (40%), generic E. coli (29%), E. coli O111 (23%), and E. coli O157 (0%). Rhamnose
      non-fermenting colonies growing on Rhamnose-McConkey agar supplemented with X
      GlcA, X-Gal, or ONPG, respectively, were blue, white, or faint yellow, whereas
      rhamnose-fermenters were red. Blue colonies from X-GlcA-containing media were the
      most well-defined and easiest to pick for further tests. All STEC O26 were MUG
      fluorescent, while STEC O157 (n = 18) were non-fluorescent. E. coli O111 and
      generic E. coli strains were either MUG-positive or-negative. Serotype-specific
      detection of STEC O26 was achieved by selecting cefixime-tellurite-resistant, MUG
      fluorescent, rhamnose-nonfermenting colonies, which carried stx1, eae beta, irp2,
      and wzx gene sequences. STEC O26 prevalence in dairy farm environmental samples
      determined using the developed isolation and genetic detection protocols was 4%.
      PFGE indicated the presence of one major cluster of E. coli O26 with 72-100% DNA
      fragment-length digest similarity among test strains. The serotype-specific
      detection methods described herein have potential for routine application in STEC
      O26 diagnosis.

PMID- 15992273
TI  - Antimicrobial resistance among gram-negative foodborne bacterial pathogens
      associated with foods of animal origin.
AB  - Antimicrobial-resistant foodborne pathogens are acquired primarily through
      consumption of contaminated food of animal origin or water. While there is much
      disagreement on the health burden imposed by resistance in foodborne bacterial
      pathogens, it is generally agreed that the use of antimicrobials, whether for
      growth promotion, prevention, or treatment, can select for resistant bacterial
      pathogens, and that these pathogens can be transmitted on food originating from
      sites processing treated animals. Information on the evolution and dissemination
      of antimicrobial resistance in foodborne pathogens shows that the situation is
      complex and differs by organism and antimicrobial. A clearer understanding of the
      ecology of resistance is needed in order to support science-based assessments of
      the public health risks due to the use of antimicrobials in the animal husbandry
      environment.

PMID- 15992274
TI  - Causes behind a human cheese-borne outbreak of gastrointestinal listeriosis.
AB  - In a previous paper, we reported an outbreak of gastrointestinal listeriosis due
      to consumption of fresh cheese made from raw milk and manufactured on a summer
      farm. The aim of the present study was to investigate why the cheese harbored
      Listeria monocytogenes. To our knowledge, this is the first documented outbreak
      of listeriosis caused by raw milk cheese where the human epidemic strain has been
      cultured from a dairy animal, whose milk has been used for cheese production. The
      conditions on a summer farm can hardly fulfil the requirements for hygienic and
      strictly controlled conditions necessary for safe processing of fresh cheese.

PMID- 15992275
TI  - Detection of a novel virulence gene and a Salmonella virulence homologue among
      Escherichia coli isolated from broiler chickens.
AB  - Despite the diversity of Escherichia coli pathotypes, there are many virulence
      genes common to isolates from food animals and humans, suggesting that
      opportunity exists for genetic exchange between human and animal isolates to
      create the next emerging, foodborne pathogen. Hemolytic activity in E. coli has
      been attributed to hemolysin genes found in either uropathogenic or
      enterohemorrhagic E. coli. These E. coli hemolysins are classified as RTX toxins
      due to a repetitive toxin domain and similar gene organization, sequence
      homology, and mechanism of action and presence in animal and human E. coli
      isolates. Certain hemolytic animal isolates, however, lack these E. coli
      hemolysin genes. Recently, we identified a hemolysin from E. coli, isolated from
      poultry, with significant homology to the K12 "silent" hemolysin gene she. This
      gene was present only in one of four hemolytic, avian E. coli isolates examined,
      suggesting that the other three E. coli contain a gene distinct from the RTX
      toxin genes, hlyA and the she homolog, hlyE. A phagemid library was made from
      chicken E. coli isolate 963726, which was negative for hemolysin gene hlyA and
      hlyE. A hemolytic clone was identified from this library, which contained a 3.3
      kb Sau3A DNA insert. The nucleotide sequences of this DNA insert revealed two,
      open reading frames (ORF). The first ORF encoded for a 40-Kdal protein with no
      significant homology to known hemolysins reported in the Gen- Bank DNA/Protein
      database. The second ORF specified a 26-Kdal protein with significant homology to
      a Salmonella regulatory gene mig-14 that had a broad distribution among the
      pathogenic, animal E. coli isolates. Deletion of the second orf did not abrogate
      hemolysis, indicating that the first ORF encoded the hemolysin. This new
      bacterial gene designated hlyF represents a new class of hemolysin.

PMID- 15992276
TI  - Problems in isolation of Campylobacter jejuni from frozen-stored raw milk and
      bovine fecal samples: genetic confirmation using multiplex PCR.
AB  - The objectives of this study were to evaluate the use of various protocols for
      the isolation of Campylobacter jejuni from bulk tank milk and bovine fecal
      samples that were stored frozen for varying times, and to develop a rapid DNA
      based protocol that distinguishes C. jejuni from other thermophilic Campylobacter
      spp. The pathogen was recovered from fecal samples that had been stored for 96
      251 days at -20 degrees C with glycerol as the cryopreservative. In a separate
      study, C. jejuni-positive bovine fecal samples were stored at 5 degrees C for up
      to 70 days without compromising subsequent recovery of the pathogen. However, the
      pathogen could not be recovered from pathogenpositive fecal samples stored with
      or without glycerol (5 mL/11 g sample) for 21 days at -20 degrees C. Bolton broth
      (BB) and Bolton broth with 5% blood (BBB), containing BB supplement, were used
      for enrichment. Bacterial isolation was achieved by streaking from BB and BBB,
      and filtering from BBB onto blood-free charcoal cefoperazone deoxycholate agar
      (CCDA). The use of BB for the recovery of Campylobacter was more sensitive than
      BBB, and streaking achieved better isolation rates than filtration. Multiplex PCR
      incorporating thermophilic Campylobacter-specific 23S rRNA and C. jejuni-specific
      hippuricase gene sequences was used to confirm C. jejuni. All 265 bulk tank milk
      samples analyzed were negative for C. jejuni, whereas five of 411 (1.2%) fecal
      samples tested positive. This is the first report that has used a combination of
      sequences of the two genes in a multiplex format to identify C. jejuni to the
      species level. The method described has potential for routine use in the
      detection of thermophilic Campylobacter in farm environmental samples as well as
      other samples.

PMID- 15992277
TI  - Accelerating bacterial identification by infrared spectroscopy by employing
      microarray deposition of microorganisms.
AB  - A microarray method for the deposition of bacteria onto an agar slide was
      developed to accelerate the formation of microcolonies. Representative
      microarrays each consisting of 40 micro-spots of five replicates of eight
      foodborne bacteria (Yersinia enterocolitica, Staphylococcus aureus, Salmonella
      typhimurium, Listeria monocytogenes, Enterobacter cloacae, Citrobacter freundii,
      Klebsiella pneumoniae, and Escherichia coli) were printed on a Brain Heart
      Infusion (BHI) agar slide using a contact micro-spotting robotic system. Within 3
      h, sufficient bacterial cells were obtained to allow accurate identification of
      the microorganism by infrared spectroscopy. This approach allows a "complete-in-a
      single-day" analysis of a large array of samples.

PMID- 15992278
TI  - Comparison of Escherichia coli Isolates from humans, food, and farm and companion
      animals for presence of Shiga toxin-producing E. coli virulence markers.
AB  - The objective of this study was to characterize Escherichia coli isolates from
      dairy cows/feedlots, calves, mastitis, pigs, dogs, parrot, iguana, human disease,
      and food products for prevalence of Shiga toxin-producing E. coli (STEC)
      virulence markers. The rationale of the study was that, isolates of the same
      serotypes that were obtained from different sources and possessed the same marker
      profiles, could be cross-species transmissible. Multiplex polymerase chain
      reaction (PCR) was used to detect presence of genes encoding Shiga toxin 1 and 2
      (stx1 and stx2), H7 flagella (flicC), enterohemolysin (hly) and intimin (eaeA) in
      E. coli isolates (n = 400). Shiga toxin-producing isolates were tested for
      production of Shiga toxins (Stx1 and Stx2 and enterohemolysin. Of the E. coli
      O157:H7/H- strains, 150 of 164 (mostly human, cattle, and food) isolates were
      stx+. Sixty-five percent of O157 STEC produced both Stx1 and Stx2; 32% and 0.7%
      produced Stx2 or Stx1, respectively. Ninety-eight percent of O157 STEC had
      sequences for genes encoding intimin and enterohemolysin. Five of 20 E. coli
      O111, 4 of 14 O128 and 4 of 10 O26 were stx+ . Five of 6 stx+ O26 and O111
      produced Stx1, however, stx+ O128 were Stx-negative. Acid resistance (93.3%) and
      tellurite resistance (87.3%) were common attributes of O157 STEC, whereas, non
      O157 stx+ strains exhibited 38.5% and 30.8% of the respective resistances. stx
      positive isolates were mostly associated with humans and cattle, whereas, all
      isolates from mastitis (n = 105), and pigs, dogs, parrot and iguanas (n = 48)
      were stx-negative. Multiplex PCR was an effective tool for characterizing STEC
      pathogenic profiles and distinguished STEC O157:H7 from other STEC. Isolates from
      cattle and human disease shared similar toxigenic profiles, whereas isolates from
      other disease sources had few characteristics in common with the former isolates.
      These data suggest interspecies transmissibility of certain serotypes, in
      particular, STEC O157:H7, between humans and cattle.

PMID- 15992279
TI  - Analysis of Bacillus anthracis spores in milk using mass spectrometry.
AB  - New approaches for identifying biological threat agents in raw milk using
      spectroscopy were tested using Bacillus anthracis (BA) Sterne strain spores
      seeded into unpasteurized bulk tank milk. Direct filtration onto Tyvek membranes
      provided the optimal filtration approach from raw milk, but detection limits were
      not ideal. When beads coated with anti-BA antibodies were mixed with spores in
      raw milk, the beads were capable of concentrating the spores that could be later
      detected and characterized by MALDI spectroscopy based on presence of previously
      characterized small acid-soluble proteins (SASP's). This approach could provide a
      very rapid assessment of whether milk or milk products have been purposefully
      contaminated with BA spores. This work was fundamentally a proof-of-concept study
      demonstrating feasibility of the approach in milk. Other parameters could be
      changed to potentially lower detection limits, and additional studies are
      currently underway to improve the approach.

PMID- 15992280
TI  - Pheno-genotyping of Salmonella enterica serotype Enteritidis isolates identified
      in Sicily during a reemergence period.
AB  - After an upward trend paralleling that occurring in most European countries,
      including Italy, since October 2002 Salmonella enterica serotype Enteritidis (S.
      Enteritidis) has again gained the first position among outbreak and sporadic
      human isolates of Salmonella in Sicily. Because phage typing of S. Enteritidis
      has many technical and epidemiological limitations and molecular methods have
      proved to be poorly discriminative for this organism, multiple typing, using
      phage typing together with pulsed field gel electrophoresis (PFGE) and plasmid
      profiling on a sample of fifty human and poultry isolates identified during the
      period October 2002 to May 2003 in Sicily, was chosen as the most valuable
      strategy to explore key features of this new epidemic wave. Although the limited
      number of strains imposes a cautious interpretation of the results, an apparently
      increasing phage type heterogeneity has emerged with rise in PT6 as the more
      striking event. While PFGE has confirmed the findings by other authors about the
      close genetic homogeneity between PT4 and PT6, plasmid profiling has provided
      discriminative patterns for PT6 strains. Combined phenotypic and genotypic
      profiles are necessary for epidemiological studies and public health
      investigations on S. enteritidis.

PMID- 15992282
TI  - The role of contaminated feed in the epidemiology and control of Salmonella
      enterica in pork production.
AB  - Food animal producers have ethical obligations to reduce the risk of foodborne
      hazards in animals under their care. Contaminated feed is a recognized source of
      Salmonella infection of food animals and regulations to control Salmonella
      contamination of animal feed have existed in some countries for decades. The
      impact of reducing Salmonella contamination of animal feeds on the risk of human
      foodborne salmonellosis is difficult to assess, and is likely to vary among food
      animal industries. In the context of U.S. pork production, factors that may
      attenuate or negate the impact (on public health) of regulatory interventions to
      control Salmonella in commercial feed include widespread use of on-farm mixing of
      swine feed; incomplete decontamination of feed during processing; post-processing
      contamination of feed at feed mills or in transportation or on-farm storage; the
      multitude of nonfeed sources of Salmonella infection; an apparently high risk of
      post-farm infection in lairage; and post-harvest sources of contamination. A
      structured survey of the extent of Salmonella contamination of animal feed in the
      United States is necessary to enable more informed debate on the feasibility and
      likely efficacy of enforcing a Salmonella-negative standard for animal feeds to
      reduce the incidence of human salmonellosis.

PMID- 15992283
TI  - Detection of Cryptosporidium parvum oocysts in experimentally contaminated
      lettuce using filtration, immunomagnetic separation, light microscopy, and PCR.
AB  - Recovery of Cryptosporidium parvum oocysts in a fecal suspension that
      experimentally contaminated onto lettuce leaves was investigated. Material
      recovered from the lettuce samples by washing in detergent solutions were
      concentrated by filtration using the Envirochek Sampling Capsule. Oocysts were
      concentrated by immunomagnetic separation (IMS) and detected by microscopy
      following modified Ziehl-Neelsen (MZN) staining. Cryptosporidal DNA was detected
      using a nested-PCR assay for amplification of a fragment of the Cryptosporidium
      oocyst wall protein (COWP) gene, which was applied to DNA extracted from both
      filtrates, and material recovered from MZN stained smears on glass slides after
      microscopy. No Cryptosporidium were detected by microscopy or by PCR of un
      inoculated lettuce leaves. After IMS, means of 0-6.5% of the total numbers of
      oocysts inoculated were recovered and detected by microscopy. Detection by PCR
      was less sensitive than microscopy. There was a strong association between
      successful PCR amplification, the numbers of oocysts detected by microscopy and
      the numbers of oocysts in the inoculum. This study confirms that C. parvum
      oocysts can be recovered from contaminated lettuce using filtration and IMS, and
      detected by microscopy and PCR. However, further developments are required to
      improve recovery of this parasite.

PMID- 15992284
TI  - Potential virulence and antimicrobial susceptibility of Campylobacter jejuni
      isolates from food and companion animals.
AB  - Infection in humans with Campylobacter jejuni is commonly associated with
      exposure to food animal fecal material. In this study, we report on the recovery,
      potential for virulence and antimicrobial resistance levels of C. jejuni isolated
      from food and companion animals. Three hundred and seventy-eight fecal samples
      from food and companion animals and surface swabs from beef carcasses were tested
      for the presence of C. jejuni. C. jejuni was isolated from 13.8% (11/80) of dogs,
      5% (1/20) of goats, 28.3% (17/60) of dairy cattle, 0% (0/65) of range cattle,
      73.5% (36/49) of feedlot cattle, and 94.7% (18/19) of beef carcasses. Beef cattle
      from a single Arizona herd showed a considerable increase in fecal shedding of C.
      jejuni from pasture to feedlot and over time on the feedlot. Forty-two isolates
      were tested for susceptibility to four antimicrobial agents, each representing a
      class of antimicrobial drug approved for use in both humans and animals. None of
      the isolates were found to be resistant to erythromycin or gentamicin, whereas
      2.4% of isolates were resistant to ciprofloxacin and 28.6% of isolates were
      resistant to tetracycline. The presence of virulence traits among the 42 isolates
      was assessed using in vitro macrophage survival and epithelial cell adherence and
      invasion assays. Of the isolates examined, 17 were able to survive within
      macrophages through 72 h at viable counts of >/=10(3)/well and 12 were capable of
      invading epithelial cells at viable counts of >/=10(3)/well. Data from these
      studies suggests that many of the isolates recovered from the non-poultry animal
      sources have the capacity to cause disease if transmitted to humans.

PMID- 15992285
TI  - Detection of Escherichia coli O157:H7 and Listeria monocytogenes in beef products
      by real-time polymerase chain reaction.
AB  - Rapid methods for the detection of Escherichia coli O157:H7 and Listeria
      monocytogenes in food products are important to the food industry and for public
      health. Conventional microbiological methods and newly developed molecular-based
      techniques such as polymerase chain reaction (PCR)-based methods are time
      consuming. In this study, a faster method based on utilization of a hybridization
      probe with real-time PCR, was developed and applied for detection of E. coli
      O157:H7 and L. monocytogenes from artificially contaminated raw ground beef and
      fully cooked beef hotdogs. Target genes for E. coli O157:H7 and L. monocytogenes
      were rfbE and hylA, respectively. An analysis of 169 bacterial strains showed
      that the chosen primers and probes were specific for detection of E. coli O157:H7
      and L. monocytogenes by real-time PCR. The assay was positive for nine of 10. E.
      coli O157:H7 strains, and all L. monocytogenes (7/7) strains evaluated. Bacterial
      strains lacking these genes were not detected by these assays. Detection limits
      of real-time PCR assays ranged from 10(3) to 10(8) colony forming units (CFU)/ml
      for E. coli O157:H7 in modified tryptic soy broth and 10(4) to 10(8) CFU/mL for
      L. monocytogenes in Fraser Broth. Detection sensitivity ranged from 10(3) to
      10(4) CFU/g of raw ground beef or hotdog without enrichment for E. coli and L.
      monocytogenes. Approximately 1.4-2.2 CFU/g of E. coli O157:H7 in raw ground beef
      were detected following an enrichment step of 4 h. Approximately 1.2-6.0 CFU/g of
      L. monocytogenes in beef hotdogs were detected following an enrichment step of 30
      h. The real-time PCR assays for detection of E. coli O157:H7 and L. monocytogenes
      in raw ground beef and beef hotdogs were specific, sensitive and rapid.

PMID- 15992286
TI  - A case study of a massive staphylococcal food poisoning incident.
AB  - In the summer of 1998, approximately 8000 individuals gathered to celebrate a
      Catholic priest's ordination in Minas Gerais, Brazil. Within hours of food
      consumption, 4000 patients experienced acute gastroenteritis, and approximately
      2000 (50%) overwhelmed Emergency Departments of 26 local hospitals. Of the
      triaged patients, 396 ( approximately 20%) required subsequent admission, and of
      these patients, 81 ( approximately 20%) were admitted to intensive care units. A
      total of 16 ( approximately 20% of those admitted to the ICU) patients progressed
      on to develop irreversible multi-system shock and expired while hospitalized. The
      trace-back investigation implicated food preparers who were culture positive for
      enterotoxigenic Staphylococcus aureus as the source of contamination. This study
      provides information on the magnitude and severity of oral exposure to
      Staphylococcal enterotoxin.

PMID- 15992287
TI  - Development and application of Real-Time PCR assays to detect fragments of the
      Clostridium botulinum types A, B, and E neurotoxin genes for investigation of
      human foodborne and infant botulism.
AB  - Real-time PCR assays for detection of Clostridium botulinum neurotoxin (BoNT)
      gene fragments specific to BoNTA, B, and E were developed as alternatives to the
      mouse bioassay. The expected specificities of the PCR assays were demonstrated by
      in silico analysis as well as empirical testing of target DNA extracted from 83
      pure cultures of C. botulinum, and 44 bacteria from other species. The
      sensitivities of the assays were found to be equivalent to 16, 10, and 141
      genomes for BoNT A, B, and E, respectively. The assays were shown to be
      applicable to both purified DNA, as well as crude DNA extracted from cultures and
      enrichment broths. The assays were evaluated using DNA extracted directly from
      clinical and food specimens as well as from inoculated broths using material
      collected from seven confirmed and one suspected case of botulism. The
      appropriate BoNT genes were detected in material from seven of the eight cases of
      botulism and provided a supportive diagnosis faster than the conventional
      bioassay. These assays have already proven useful for pubic health
      microbiological investigation of suspected cases of human botulism by
      substantially improving the diagnostic process.

PMID- 15992288
TI  - Detection of viable Mycobacterium avium subsp. paratuberculosis using luciferase
      reporter systems.
AB  - Plasmid- and phage-based firefly luciferase reporter constructs were evaluated as
      rapid detection systems for viable Mycobacterium avium subsp. paratuberculosis
      (MAP). A MAP strain bearing a luciferase-encoding plasmid was detectable at 100
      cells/mL in skim milk and 1000 cells/mL in whole milk. Three luciferase-encoding
      mycobacteriophage were evaluated for detection of wild-type MAP. The best of
      these, phAE85, allowed detection of >1000 cells/mL within 24-48 h. Membrane
      filtration did not improve the sensitivity of detection for either plasmid or
      phage reporters. Luciferase reporters show promise for rapid detection of viable
      MAP.

PMID- 15992289
TI  - Inactivation of Escherichia coli O157:H7 by high-intensity ultrasonication in the
      presence of salts.
AB  - Inactivation of Escherichia coli O157:H7 suspended in salt solutions (Na(2)PO(4),
      NaCl, NaNO(3), NH(4)Cl, CaCl(2), and AlCl(3)) at concentrations ranging from 0 to
      5% (w/v) by high-intensity ultrasound at two different temperature conditions
      (ice water bath, 40 degrees C water bath) and three ultrasonic intensity levels
      (9.5, 21.8, 49.2 W/cm(2)) was determined. Increases in sonication treatment time,
      intensity, and temperature led to increased lethality of E. coli O157:H7.
      However, cell lethality, as a function of solute concentration, varied depending
      upon type of salt. CaCl(2), NaCl, NaNO(3), Na(2)PO(4), and NH(4)Cl had little or
      no effect on survival of E. coli O157:H7 (<1-log reduction) regardless of other
      treatment conditions at 9.5 W/cm(2). Concentrations of >0.5% of CaCl(2), NaNO(3),
      Na(2)PO(4), and NH(4)Cl adversely affected survival (1.0- to 1.6-log reduction)
      with treatment of 21.8 W/cm(2) in an ice bath and showed greater inactivation
      (1.2-4.0-log reduction) in the 40 degrees C water bath. Treatment of 49.2 W/cm(2)
      showed the greatest impact regardless of other parameters. In the 40 degrees C
      water bath, treatment for 10 min at 49.22 W/cm(2) led to total inactivation for
      cells suspended in 0.5% NH(4)Cl, 1% CaCl(2), 2% NaCl, 5% Na(2)PO(4), and all
      concentrations of AlCl(3). Complete inactivation also occurred in an ice bath for
      5% AlCl(3), which was shown to be the most effective salt. The most efficient
      treatment combination was in the 40 degrees C water bath for 10 min at 49.2
      W/cm(2) with 5% AlCl(3). Inactivation of E. coli O157:H7 is attributed to
      cavitation-induced shear forces, reaction of cavitation-generated hydrogen
      peroxide with microbial cell wall constituents and electrostatic interactions of
      dissociated salts with cell membranes.

PMID- 15992290
TI  - A comparison of acute phase protein measurements and meat inspection findings in
      cattle.
AB  - The acute phase proteins haptoglobin (Hp) and serum amyloid-A (SAA) are increased
      in the blood of cattle with infectious or inflammatory diseases. As it is
      important to identify such cattle at meat inspection, a study was undertaken to
      compare the levels of Hp and SAA in blood samples from cattle at abattoir with
      the post-mortem meat inspection findings. The serum concentrations of Hp and SAA
      were determined in healthy beef cattle (n = 16); healthy dairy cows with no
      pathological conditions (n = 22); and cows with pathologic conditions (n = 62).
      The last group was subdivided into cows with acute pathological conditions (n =
      10) and those with non-acute pathological conditions (n = 52). The mean (+/-SD)
      Hp levels in plasma from beef cattle and cows without pathological conditions
      found were 0.11 +/- 0.08 mg/mL and 0.02 +/- 0.03 mg/mL, respectively, and the
      difference was statistically significant (p < 0.001). However, mean Hp level in
      cattle with pathological conditions was 0.27 +/- 0.40 mg/mL, significantly higher
      than the mean values of either group of healthy animals (p < 0.01 versus healthy
      dairy cows and p < 0.001 versus healthy beef cattle). The mean SAA concentration
      in plasma samples from 22 healthy dairy cows (with no pathological conditions
      found) was 51 +/- 38 microg/mL, significantly higher (p < 0.01) than the mean SAA
      value of 29 +/- 21 microg/mL calculated from 16 plasma samples from healthy beef
      cattle. In the group of 62 cows with pathological conditions, the mean SAA level
      was 94 +/- 115 microg/mL being significantly higher than the respective value in
      either groups of healthy animals (p < 0.01 versus healthy cows and p < 0.001
      versus healthy beef cattle). Considerations of the acute phase proteins results
      obtained from the animals with pathological conditions did not reveal a clear
      association between acute phase proteins levels and respective specific
      pathological conditions, although there was a significant correlation between Hp
      and SAA concentrations at the individual animal level when all results were
      considered (R = 0.75, n = 100, p < 0.001). Nevertheless, when the dairy cows with
      pathological conditions were subdivided, some significant differences in mean
      values of acute phase proteins were observed enabling differentiation between
      animals with (broadly categorised) acute and non-acute pathological conditions.
      Significantly higher Hp (p < 0.05) and SAA (p < 0.05) concentrations were found
      in the acute pathology group than in the non-acute pathology group. Overall, the
      result of the present study indicated that the acute phase protein analysis could
      be an additional and useful tool enabling separation of "suspect" from "non
      suspect" animals during ante mortem inspection within a modernised meat
      inspection system.

PMID- 15992291
TI  - Frequency of brain tissue embolism associated with captive bolt gun stunning of
      sheep.
AB  - In accordance with controls instituted to protect the consumer from meat
      potentially infected with bovine spongiform encephalopathy (BSE), brain tissue
      emboli caused by the use of captive bolt gun (CBG) stunning have been identified
      as a potential public health risk that requires further investigation. As the
      natural occurrence of BSE in sheep remains uncertain we have investigated the
      frequency of brain tissue embolism associated with stunning by two types of CBG
      that are in commercial use in the United Kingdom. Blood samples collected from
      sheep following stunning were analysed by ELISA as well as by a combination of
      microscopy and immunocytochemistry. The combined positive results from each
      method of sample analysis were used to determine the frequency of brain tissue
      embolism in the sample population. The frequency of brain tissue embolism was
      found to be 23% in sheep stunned with a cartridge-activated CBG (95% confidence
      interval of 15.8-32.2%) and 14% in those stunned with a pneumatically activated
      CBG (95% confidence interval of 8.5-22%). The frequency of brain tissue embolism
      associated with the use of CBG stunning may represent a significant source of
      carcass contamination with brain tissue.

PMID- 15992292
TI  - Recovery of Salmonella spp. from raw produce surfaces using ultrasonication.
AB  - Fresh fruits and vegetables have been increasingly associated with outbreaks of
      foodborne illness. Microorganisms on the surface of raw produce may be difficult
      to remove for decontamination or microbial sampling due to entrapped or attached
      cells and porous surfaces. The objective of this study was to determine if
      ultrasonic treatment using 40 kHz with varying temperatures and agitation times
      can enhance removal and recovery of Salmonella spp. from raw produce surfaces.
      Strawberry, apple, and cantaloupe surfaces were spot inoculated with a fivestrain
      cocktail of nalidixic acid-resistant Salmonella spp. Produce were immersed in
      0.1% buffered peptone water in either a Whirl-Pak bag for manual shaking (60 sec)
      or a sterile beaker for ultrasonic treatment (60 or 120 sec). Diluent
      temperatures of either 25 degrees C or 40 degrees C were used with these sampling
      protocols. Diluents were spiral plated onto tryptic soy agar supplemented with 50
      ppm of nalidixic acid. No significant differences were observed between each
      Salmonella recovery method for each produce type. In this study, ultrasonic
      treatment using 40 kHz did not enhance recovery of Salmonella spp. from produce
      surfaces. The ultrasonic frequency, temperatures, and times used in this study
      did not enhance or diminish bacterial recovery. Additional research is still
      needed to determine the efficacy of other ultrasonic frequencies, diluents, and
      diluent temperatures for enhancing the recovery and enumeration of Salmonella
      spp. and other microorganisms from raw produce surfaces.

PMID- 15992293
TI  - Epidemiologic research in food safety.

PMID- 15992294
TI  - Epidemiology and food safety.
AB  - With the introduction of the Food Safety Initiative in 1997, food safety
      activities and research funding have increased dramatically. Advances in
      microbiological methods and epidemiologic research have provided significant
      progress in our understanding of foodborne diseases and in our implementation of
      control programs. This article highlights some of those food safety activities
      and epidemiologic research programs. This article also describes potential future
      research areas and activities.

PMID- 15992295
TI  - Molecular typing of Campylobacter strains using the cmp gene encoding the major
      outer membrane protein.
AB  - Thermophilic Campylobacter, particularly Campylobacter jejuni, is one of the
      major foodborne human pathogens of animal origin. Reliable and sensitive typing
      tools are required for understanding the epidemiology and ecology of this
      zoonotic bacteria agent. Currently, several molecular typing methods are
      available for differentiating Campylobacter strains, but each of them has
      limitations. Our previous study revealed that considerable sequence polymorphism
      exists in the cmp gene encoding the major outer membrane protein of Campylobacter
      and suggested that sequence variation of cmp may be utilized for discrimination
      of Campylobacter strains. In this study, we evaluated the feasibility of the cmp
      based typing tool, using pulsed-field gel electrophoresis (PFGE) as the "gold"
      standard for comparison. The cmp alleles were sequenced from multiple
      Campylobacter strains, grouped, and compared with the PFGE profiles of these
      strains using Bionumerics. Results showed that 43 cmp sequence types and 43 PFGE
      types existed among the 60 Campylobacter isolates. Typeability of these strains
      is 100% using either the cmp-based method or PFGE. The discrimination indices are
      0.973 for the cmp-based method and 0.969 for PFGE, respectively. The cmp sequence
      types are 77.6% congruent with the PFGE types. These results indicate that the
      cmp-based typing is a simple, yet highly discriminatory approach for molecular
      differentiation of C. jejuni strains.

PMID- 15992296
TI  - Patterns of antimicrobial resistance among commensal Escherichia coli isolated
      from integrated multi-site housing and worker cohorts of humans and swine.
AB  - We examined antimicrobial resistance (AR) phenotypes among commensal Escherichia
      coli isolated from fecal matter of humans and swine housed in a semi-closed and
      uniquely integrated multi-site farrow-to-plate operation. Aggregate cohorts of
      humans consisted of (1) "control" groups of consumers, (2) groups of swine
      workers, and (3) groups of slaughter-plant workers. Analyses of cross-sectional
      AR data from 472 human and 376 swine isolates are presented. AR phenotypes among
      these isolates were compared by (1) host species, (2) facility location, (3)
      facility type, (4) housing (human) or production (swine) cohort, and (5) sample
      collection period and time of day. There were significant (p < 0.05) differences
      in isolates among host-species with swine uniformly at greater risk for (1) AR to
      four specific antimicrobials (kanamycin, streptomycin, sulfamethoxazole,
      tetracycline), and (2) multiple resistance phenotypes (p < 0.0001). Facility type
      and unit location were more often associated with AR differences among swine
      isolates than among human isolates. Swine production group was significantly
      associated with AR prevalence (p < 0.05) for nine antimicrobials; in general,
      purchased boars, suckling piglets, weaned piglets, and lactating sows were at
      higher risk of AR. There was no significant (p > 0.05) association of human
      occupational/consumer cohort with AR prevalence. Several unique AR phenotypes
      were detected in each of the human- and swine-intake groups. These data establish
      baseline characteristics for an on-going 3-year longitudinal study designed to
      further characterize AR phenotype and genotype in this population. Host-,
      facility-, and cohort-specific data demonstrate that sufficient prevalence
      differences exist to permit the future quantification of AR transmission, should
      it occur. Based on these cross-sectional data, occupational exposure to either
      swine-rearing or swine-slaughter facilities does not appear to be associated with
      the prevalence of phenotypic resistance among the commensal fecal E. coli
      isolated from this integrated system.

PMID- 15992297
TI  - Contamination of retail foods, particularly turkey, from community markets
      (Minnesota, 1999-2000) with antimicrobial-resistant and extraintestinal
      pathogenic Escherichia coli.
AB  - To assess the food supply as a possible vehicle for antimicrobial-resistant and
      extraintestinal pathogenic Escherichia coli (ExPEC), we defined the prevalence,
      density, clonal diversity, virulence characteristics, and antimicrobial
      resistance profiles of E. coli among diverse retail food items. A microbiological
      survey was undertaken of 346 food items (vegetables, produce, beef, pork,
      chicken, and turkey) purchased as a convenience sample from 16 retail markets
      within the Minneapolis-St. Paul area in 1999-2000, with selective cultures for E.
      coli and extensive molecular and phenotypic characterization of E. coli isolates.
      Meats, particularly turkey products, were often extensively contaminated with
      antimicrobial-resistant E. coli and ExPEC, to a much greater extent than were
      produce items, even those from farmer's markets. Moreover, meat-source E. coli
      differed substantially from produce-source E. coli with respect to phylogenetic
      background (more commonly from virulence-associated phylogenetic groups B2 or D),
      virulence genotype (more extensive), and antimicrobial resistance profile (more
      extensive). Molecular typing methods matched four turkey-source isolates to
      selected human clinical and fecal isolates representing the O7:K1:H-, O83:K1, and
      O73/O77:K52:H18 ("clonal group A") clonal groups of ExPEC. Meats purchased in
      grocery stores, particularly turkey products, are frequently contaminated with
      antimicrobial-resistant E. coli and ExPEC. Further study is needed regarding the
      origins and health consequences of these foodborne organisms, both to clarify the
      need for and to guide the possible development of appropriate regulatory and
      monitoring systems and preventive interventions.

PMID- 15992298
TI  - Use of rope devices to describe and explain the feedlot ecology of Escherichia
      coli O157:H7 by time and place.
AB  - Escherichia coli O157:H7 is an important pathogen of humans, and cattle
      populations serve as an important reservoir for human exposure. The organism is
      ubiquitous to feedlot cattle populations, although the nature of its occurrence
      is quite dynamic. Why E. coli O157:H7 varies by time and place in fed cattle is
      poorly understood. This study was designed to describe and explain the occurrence
      of E. coli O157:H7 by pen-level factors of time and place. From each pen, we
      cultured seven ropes placed within pens for cattle to rub and chew (ROPES), in
      order to classify the pens as high or low prevalence in longitudinal studies
      conducted during the summer and winter feeding periods of 2 full years. We
      observed differences in occurrence of ROPES-positive pens by season, weeks within
      season, and feedyard. ROPES-positive pens clustered temporally. Factors
      associated with ROPES-positive pen-weeks during both the summer and winter
      feeding periods were feedyard, prior 7-day mean air temperature, recovery of E.
      coli O157:H7 from the composite fecal sample, and recovery of E. coli O157:H7
      from the water tank. Pens of summer-fed cattle were less likely to be ROPES
      positive for E. coli O157:H7 if the ROPES were positive for Salmonella spp. The
      condition of the pen surface was associated with the likelihood for winter-fed
      pens of cattle to be ROPES-positive. We were able to monitor these pens of cattle
      using ROPES at minimal cost and without disturbing individual cattle. These
      observations improve our understanding of the ecology of E. coli O157:H7 in fed
      cattle, and also illustrate the importance of designing and analyzing
      observational studies and clinical trials to account for time- and place
      dependent variables that affect the probability of detecting E. coli O157:H7.

PMID- 15992299
TI  - Use of rope devices to describe and explain the feedlot ecology of Salmonella by
      time and place.
AB  - Salmonella spp. are important zoonotic pathogens, and cattle can serve as an
      important source of this organism for human exposure through food. This study was
      designed to describe and explain the occurrence of Salmonella spp. by pen-level
      factors of time and place using a pen-level test-method previously validated for
      E. coli O157:H7. From each pen, we cultured seven ropes placed within the pen for
      cattle to rub and chew (ROPES), in order to classify the pens as ROPES-positive
      or ROPES-negative each week in longitudinal studies conducted during the summer
      and winter feeding periods of 2 full years. We observed differences in occurrence
      of ROPES-positive pens by week within each season such that, at times, a high
      proportion of pens were of the same ROPES-status even though feedyards were
      separated by 50-200 km. Factors associated with ROPES-positive pen-weeks during
      both the summer and winter feeding periods were the condition of the pen surface
      and recovery of Salmonella spp. from the water tank. The probability for pens of
      summer-fed cattle to be ROPES-positive for Salmonella spp. increased as the
      number of cattle in the pen increased and decreased when the pen was ROPES
      positive for E. coli O157:H7. Pens of winter-fed cattle differed by feedyard in
      the probability of their being ROPES-positive for Salmonella spp. We were able to
      monitor these pens using ROPES at minimal expense, without disturbing individual
      cattle, and observe important time and place relationships of Salmonella spp. in
      fed cattle. These observations illustrate the importance of accounting for time-
      and place-dependent variables that affect the probability of detecting Salmonella
      spp. when designing and analyzing observational studies and clinical trials.

PMID- 15992300
TI  - Prevalence of and risk factors for Escherichia coli O157 in market-ready beef
      cattle from 12 U.S. feedlots.
AB  - Determination of Escherichia coli O157 prevalence immediately prior to shipment
      and harvest is an important facet of the ecology of this organism, which requires
      further elucidation. As part of a larger study to measure the effects of within
      pen prevalence of E. coli O157 on subsequent carcass contamination, fecal samples
      from 15 pens of cattle in each of 12 different feedlots in three states
      (Colorado, Nebraska, and Montana) were collected from June through September
      2002. Thirty fresh fecal samples were collected from each pen floor within 36 h
      of shipment to slaughter. Fecal samples underwent standard enrichment,
      immunomagnetic separation, and isolation procedures for E. coli O157.
      Multivariable logistic regression was used to determine which factors best
      predicted pen-level positive culture results, and to estimate the magnitude of
      association between each factor and the outcome, while adjusting for other
      factors in the model. Thirteen (86.7%) of the 15 pens had at least one positive
      sample, and the within-pen prevalence of E. coli O157 in positive pens ranged
      from 3.3% to 77.8%. The odds of E. coli O157 positive fecal samples from cattle
      fed brewers grains were six times that for cattle not fed brewers grains. The
      odds of E. coli O157 positive fecal samples from pens of cattle from Central
      Nebraska was nine times that for pens of cattle from Eastern Colorado. These data
      demonstrate that the presence of E. coli O157 in fecal samples from finished
      feedlot cattle is associated with feeding of brewers grain and geographic
      location. Additional studies to further characterize geographic distribution of
      E. coli O157 and to investigate pen-level intervention strategies should be
      conducted.

PMID- 15992301
TI  - Variable abattoir conditions affect Salmonella enterica prevalence and meat
      quality in swine and pork.
AB  - Research suggests that abattoir holding pens pose significant Salmonella enterica
      risk to swine immediately preharvest. The goal of this study was to evaluate
      those factors related to holding that increased the prevalence of S. enterica in
      swine at slaughter. To accomplish this goal, we focused on holding time and
      flooring. Our objectives were to (1) compare Salmonella enterica prevalence among
      pigs held for short (15-45 min) versus long (up to 4 h) periods before slaughter;
      and (2) determine the impact of flooring (slatted vs. concrete) as it relates to
      the prevalence of S. enterica. The study consisted of seven repetitions at a
      large volume (11,000 head/day) Midwest abattoir. Each repetition consisted of one
      truck load of pigs (n = 170) sorted into one of three groups: (1) animals held
      for a short time (15-45 min) on solid floors (short-hold); (2) animals held for 4
      +/- 0.5 h on slatted floors; and (3) animals held for 4 +/- 0.5 h on solid
      concrete floors. At slaughter, samples were collected from 30 pigs in each group.
      Cecal contents (20 mL), feces (20 g), and the ileocecal lymph node were cultured
      for S. enterica. Additionally, the effect of holding time on meat quality
      parameters (loin pH at 35 min and 6 h, color, drip loss) was evaluated for the
      first four replicates. The proportion of S. enterica-positive samples was highest
      (p < 0.05) in the cecum of pigs held on solid concrete floors (72.4%), and
      slightly less for pigs held on slatted floors (63.3%). Animals held for less than
      45 min before slaughter demonstrated the lowest proportion of S. enterica
      positive samples (52.9%). The pig prevalence, as measured by any one of the three
      samples being positive, was significantly different (p < 0.05) between animals
      held on solid floors (81%) and those animals held for 45 min or less before
      slaughter (69%). Meat quality, as measured by multiple parameters, was adversely
      affected by lack of a rest period. The mean 24-h pH was significantly lower for
      the short-hold group compared to the other two groups. The mean Minolta L and the
      drip loss were significantly higher in the short-hold group. From this and other
      studies, it appears that elimination of the holding process is not feasible S.
      enterica control option, given current U.S. harvesting systems.

PMID- 15992302
TI  - Occurrence of Campylobacter spp. in cecal contents among commercial broilers in
      iceland.
AB  - Campylobacter jejuni remains the most frequently reported bacterial cause of
      human gastroenteritis in Nordic countries. The primary source of transmission to
      humans is suggested as mishandled raw poultry or consuming improperly prepared
      chicken. The focus of this report was to characterize the prevalence and cell
      numbers of the organism within the commercial Icelandic poultry industry.
      Commercial broiler flocks were sampled from May 2001 through 2003 in a total
      population study. At the slaughter plant, 40 randomly selected ceca were obtained
      from each flock, pooled into four samples containing 10 ceca each, and analyzed.
      Cell numbers and prevalence of Campylobacter spp. were estimated by direct
      plating of dilutions onto Campy-Cefex agar and incubating the plates at 42
      degrees C under microaerobic atmosphere; colonies were confirmed as Campylobacter
      spp. by microscopy and latex agglutination to provide quantification of cell
      numbers per gm of cecal material. A total of 15.4% of the flocks carried the
      organism at at a maximum cell number of 8.1 x 10(7) cfu/g, having a mean raw
      count of colonized birds at 1.3 x 10(7) cfu/g (geometric mean of 1.5 x 10(6)).
      During the 3 years of sampling, the prevalence ranged from 17.6% to 17.3% to
      12.7% for slaughter years 2001, 2002, and 2003, respectively. Isolation rates
      varied with numbers of catch lots (groups of birds taken for slaughter)/flock;
      with one catch lot/flock, the prevalence was 13.7%, with two 17.5%, and with
      three 33.3%. With increased flock size, isolation rates also increased; flocks of
      greater than 5,000 birds had a prevalence of 12.0% positive, 14.0% of flocks with
      5,000-10,000 birds were positive, and 25.5% of flocks with more than 10,000 birds
      were positive for Campylobacter spp. Isolation rates varied with the processing
      lines: M was positive at 17.3%, B was positive at 10.1%, and G at 17.2%. Flocks
      were more frequently colonized in the warmer months, and younger birds were less
      frequently colonized than were older slaughtered birds. This study provides
      descriptive microbiology pertaining to Iceland broilers in a total population
      study.

PMID- 15992303
TI  - Vertical and horizontal transmission of salmonella within integrated broiler
      production system.
AB  - Salmonella remains one of the leading causes of food-borne illness in the United
      States, and many key questions regarding the introduction and persistence in
      animal production systems still remain. In order to understand the ecology of
      Salmonella within an integrated commercial broiler production system, 289
      Salmonella enterica were recovered from two integrated poultry farms during the
      production and processing of seven consecutive flocks. The variety and prevalence
      of Salmonella serotypes differed between farms. Overall, 15 serotypes were
      identified, with the most common being Typhimurium (55%), Montevideo (7.9%),
      Kentucky (9%), and Enteritidis (9.7%). Salmonella Typhimurium and Enteritidis
      isolates recovered from processed carcasses from Farm One were further
      characterized using pulsed-field gel electrophoresis (PFGE), and were shown to be
      indistinguishable from isolates recovered from the poultry house environment and
      mice trapped on this farm. Additionally, the same broiler S. Typhimurium and S.
      Enteritidis strains, identified by PFGE, were also isolated from samples taken at
      a company breeder farm, suggesting vertical transmission of these Salmonella
      serotypes in this poultry production system. Results indicate that management
      practices at the breeder level may have a profound effect on the transmission and
      persistence of salmonellae within an integrated production system, as well as on
      the potential contamination of poultry-derived products.

PMID- 15992304
TI  - Strain persistence and fluctuation of multiple-antibiotic resistant Campylobacter
      coli colonizing turkeys over successive production cycles.
AB  - The dynamics of colonization of turkeys by thermophilic campylobacters that are
      resistant to multiple antibiotics is poorly understood. In this study, we
      monitored cecal colonization of turkeys by Campylobacter over three successive
      production cycles at the same farm. Campylobacter isolated from the ceca was
      predominantly C. coli in all three flocks. Isolates with two distinct fla types
      that represented a single clonal group based on pulsed-field gel electrophoresis
      and that were resistant to multiple antibiotics (tetracycline, streptomycin,
      ampicillin, erythromycin, kanamycin, nalidixic acid, and ciprofloxacin)
      predominated throughout the three production cycles. The relative prevalence of
      each fla type, however, varied significantly from one flock to the next. The
      repeated isolation of these multiresistant C. coli from successive flocks likely
      reflected persistence of the organisms in currently unknown reservoirs in the
      production environment or, alternatively, repeated introduction events followed
      by establishment of these bacteria in each successive flock.

PMID- 15992305
TI  - Genotypes and antibiotic resistance of salmonella newport isolates from U.S.
      market oysters.
AB  - The consumption of raw oysters contributes to food-borne diseases such as
      salmonellosis. Prevalence studies in our laboratory have shown that Salmonella
      spp. were present in 7.4% of U.S. market oysters, with the majority (78/101) of
      isolates being of the Salmonella enterica Newport serovar. E-tests were performed
      to assess the susceptibility of the S. Newport oyster isolates to antibiotics
      used for treatment of Salmonella infections. The oyster isolates were susceptible
      to Gentamicin, Trimethoprim/Sulphamethoxazole, and Ciprofloxacin, while for the
      most part they were resistant to Ampicillin and Tetracycline. Consistent with the
      uniform antibiotic susceptibility profile of these isolates, only three pulsed
      field gel electrophoresis (PFGE) profiles were identified among the isolates. Of
      these three profiles, one was present in 63 of the 78 isolates, indicating not
      only the presence of S. Newport in oysters, but the predominance of a single PFGE
      type.

PMID- 15992306
TI  - Foodborne pathogens in milk and the dairy farm environment: food safety and
      public health implications.
AB  - Milk and products derived from milk of dairy cows can harbor a variety of
      microorganisms and can be important sources of foodborne pathogens. The presence
      of foodborne pathogens in milk is due to direct contact with contaminated sources
      in the dairy farm environment and to excretion from the udder of an infected
      animal. Most milk is pasteurized, so why should the dairy industry be concerned
      about the microbial quality of bulk tank milk? There are several valid reasons,
      including (1) outbreaks of disease in humans have been traced to the consumption
      of unpasteurized milk and have also been traced back to pasteurized milk, (2)
      unpasteurized milk is consumed directly by dairy producers, farm employees, and
      their families, neighbors, and raw milk advocates, (3) unpasteurized milk is
      consumed directly by a large segment of the population via consumption of several
      types of cheeses manufactured from unpasteurized milk, (4) entry of foodborne
      pathogens via contaminated raw milk into dairy food processing plants can lead to
      persistence of these pathogens in biofilms, and subsequent contamination of
      processed milk products and exposure of consumers to pathogenic bacteria, (5)
      pasteurization may not destroy all foodborne pathogens in milk, and (6)
      inadequate or faulty pasteurization will not destroy all foodborne pathogens.
      Furthermore, pathogens such as Listeria monocytogenes can survive and thrive in
      post-pasteurization processing environments, thus leading to recontamination of
      dairy products. These pathways pose a risk to the consumer from direct exposure
      to foodborne pathogens present in unpasteurized dairy products as well as dairy
      products that become re-contaminated after pasteurization. The purpose of this
      communication is to review literature published on the prevalence of bacterial
      foodborne pathogens in milk and in the dairy environment, and to discuss public
      health and food safety issues associated with foodborne pathogens found in the
      dairy environment. Information presented supports the model in which the presence
      of pathogens depends on ingestion of contaminated feed followed by amplification
      in bovine hosts and fecal dissemination in the farm environment. The final
      outcome of this cycle is a constantly maintained reservoir of foodborne pathogens
      that can reach humans by direct contact, ingestion of raw contaminated milk or
      cheese, or contamination during the processing of milk products. Isolation of
      bacterial pathogens with similar biotypes from dairy farms and from outbreaks of
      human disease substantiates this hypothesis.

PMID- 15992307
TI  - Heat-treated Campylobacter spp. and mRNA stability as determined by reverse
      transcriptase-polymerase chain reaction.
AB  - The detection method of reverse transcriptase-polymerase chain reaction (RT-PCR),
      which specifically targets mRNA, was developed and tested for detection of
      cultivable Campylobacter spp. The expression of four DNA targets- flaA, tkt,
      porA, and a putative haem-copper oxidase domain-were assayed in heat-inactivated
      Campylobacter spp. to determine an optimum target for RT-PCR amplification. A
      diversity of Campylobacter spp. was tested; however, the presented RT-PCR
      technique was specific for C. jejuni, C. coli, and C. lari. The durability of
      mRNA species detected by our RT-PCR technique was dependent upon the individual
      Campylobacter spp. examined, the condition of heat treatment and post-treatment
      holding time, as well as the transcript targeted. The putative oxidase was
      determined to be the most stable mRNA species for this assay. The mRNA of the
      putative oxidase gene was detectable even after Campylobacter spp. had been
      treated at temperatures of 95-99 degrees C. Using DNA-based PCR, the four DNA
      targets could be amplified after heat inactivation followed by a 48 h holding
      time, indicating that the chromosomal DNA was not substantially degraded by the
      heat treatment. PCR products from the putative oxidase gene were detected at
      10(2) to 10(3) C. jejuni CFU per mL, exhibiting the highest level of sensitivity
      among the genes tested. The results in the present study indicate that mRNA from
      Campylobacter spp. may persist in a form that is detectable by RT-PCR
      amplification for an extended period after heat treatment, demonstrating a poor
      correlation between mRNA detection and cell cultivability. With these results in
      mind, further investigations are necessary to determine the correlation between
      RT-PCR amplification and viability.

PMID- 15992308
TI  - Effect of the implementation of HACCP on the microbiological quality of meals at
      a university restaurant.
AB  - A study was conducted to evaluate the microbiological quality, including total
      mesophilic counts and markers of bacteriological hygiene, as indicator of food
      safety of three categories of the most consumed meals in a university restaurant,
      before and after implementation of the HACCP system and personnel training. Cold
      gastronomy products, cooked warm-served products, and cooked cold-served products
      were tested for bacterial contamination. Throughout the experiment, 894 samples
      were examined for total counts of aerobic bacteria, counts of indicator organisms
      (coliform organisms and Escherichia coli) and pathogens (Staphylococcus aureus,
      Bacillus cereus, Salmonella spp., and Listeria monocytogenes). Implementation of
      the HACCP system, together with training in personnel hygiene, good manufacturing
      practices, and cleaning and sanitation procedures, resulted in lower aerobic
      plate counts and a lower incidence of S. aureus, coliform organisms, E. coli, and
      B. cereus, whereas Salmonella spp. and L. monocytogenes were not found in all
      samples studied. The microbial results of this study demonstrate that personnel
      training together with HACCP application contributed to improve the food safety
      of meals served in the restaurant studied.

PMID- 15992309
TI  - Establishment of minimum operational parameters for a high-volume static chamber
      steam pasteurization system (SPS 400-SC) for beef carcasses to support HACCP
      programs.
AB  - A static chamber steam pasteurization unit (SPS 400-SC()) was installed in a high
      volume commercial beef slaughter facility. The SPS 400-SC consists of a three
      phase carcass treatment cycle of water removal, steam pasteurization, and water
      chilling. Seven chamber temperatures (71.1, 73.9, 76.7, 79.4, 82.2, 85.0, and
      87.8 degrees C) were evaluated at the midline area of pre-rigor beef carcasses.
      For each temperature evaluated, 20 carcass sides were randomly selected and
      aseptically sampled by tissue excision immediately before and after steam
      pasteurization to determine total aerobic bacteria, Enterobacteriaceae, generic
      E. coli, and total coliform populations. The 87.8 and 85.0 degrees C treatment
      temperatures were highly effective at reducing total aerobic bacterial
      populations, with log(10) reductions of 1.4 and 1.5 CFU/cm(2), respectively, from
      pretreatment mean population levels of 1.7 and 1.9 log10 CFU/cm(2). These
      temperatures also reduced Enterobacteriaceae, total coliforms, and generic E.
      coli to undetectable levels (<0.4 CFU/cm(2)) on all carcasses sampled. Treatment
      at 82.2 was marginally effective at reducing bacterial populations, while 71.1,
      73.9, 76.7, and 79.4 degrees C treatments were ineffective at reducing microbial
      populations. In a Hazard Analysis Critical Control Points (HACCP)-based system
      employing steam pasteurization of carcasses as a critical control point, a
      critical limit of 85.0 degrees C as a minimum chamber temperature should be
      established, with a targeted operating temperature of 87.8 degrees C providing
      optimum antimicrobial activity.

PMID- 15992310
TI  - Development and evaluation of a real-time fluorescent polymerase chain reaction
      assay for the detection of bovine contaminates in cattle feed.
AB  - A real-time fluorescent polymerase chain reaction assay for detecting prohibited
      ruminant materials such as bovine meat and bone meal (BMBM) in cattle feed using
      primers and FRET probes targeting the ruminant specific mitochondrial cytochrome
      b gene was developed and evaluated on two different types of cattle feed. Common
      problems involved with PCR based testing of cattle feed include the presence of
      high levels of PCR inhibitors and the need for certain pre-sample processing
      techniques in order to perform DNA extractions. We have developed a pre-sample
      processing technique for extracting DNA from cattle feed which does not require
      the feed sample to be ground to a fine powder and utilizes materials that are
      disposed of between samples, thus, reducing the potential of cross contamination.
      The DNA extraction method utilizes Whatman FTA card technology, is adaptable to
      high sample throughput analysis and allows for room temperature storage with
      established archiving of samples of up to 14 years. The Whatman FTA cards are
      subsequently treated with RNAse and undergo a Chelex-100 extraction (BioRad,
      Hercules, CA), thus removing potential PCR inhibitors and eluting the DNA from
      the FTA card for downstream PCR analysis. The detection limit was evaluated over
      a period of 30 trials on calf starter mix and heifer starter ration feed samples
      spiked with known concentrations of BMBM. The PCR detection assay detected 0.05%
      wt/wt BMBM contamination with 100% sensitivity, 100% specificity, and 100%
      confidence. Concentrations of 0.005% and 0.001% wt/wt BMBM contamination were
      also detected in both feed types but with varying levels of confidence.

PMID- 15992311
TI  - Detection of Campylobacter jejuni in dairy farm environmental samples using SYBR
      Green real-time polymerase chain reaction.
AB  - The aim of this study was to evaluate a SYBR Green based real-time PCR assay
      using well-characterized primers to detect Campylobacter jejuni in naturally
      contaminated dairy farm environmental samples. Specificity of the assay was
      determined with 62 C. jejuni strains and 120 non-C. jejuni strains. Peak melting
      temperature obtained with melting curves specific for C. jejuni was 77.5 degrees
      C. Standard curves were constructed using mean threshold cycle (C(T)) and various
      concentrations of C. jejuni ranging from 10(0) to 10(8) colony forming units
      (CFU)/mL, which resulted in a linear relationship between C(T) and log input DNA.
      Correlation coefficients of standard curves based on pure culture of C. jejuni in
      broth and spiked cells in lagoon water were R(2) = 0.995 (slope = 3.21) and R(2)
      = 0.988 (slope = 3.22), respectively, and sensitivity limits were <10 and >10(3)
      CFU/mL, respectively. After 24-h enrichment, total C. jejuni counts of all
      samples spiked with 10(0) CFU/mL reached >10(5) CFU/mL, and the detection limit
      was improved from >10(3) CFU/mL to <10 CFU/mL of inoculum in broth. Eighty-two
      dairy farm environmental samples, including fecal slurry, feed/silage, lagoon
      water, drinking water, bulk tank milk, farm soil, and bedding material, were
      analyzed. The real-time PCR assay detected C. jejuni in 25 (30.4%) of 82 samples,
      with 17 (68%) of these samples being culture positive for C. jejuni. All samples
      that were positive by standard culture methods were also positive by the real
      time PCR method. Mean C( T ) values of 48-h enriched cultures for 17 PCR
      positive/culture-positive samples and eight PCR-positive/culture-negative samples
      were 21.4 +/- 3.6, and 34.6 +/- 1.5 (p < 0.0001), respectively. C( T ) values for
      negative samples were >38.0. These results indicate that the SYBR Green real-time
      PCR assay provides a specific, reproducible, and simple method for detecting C.
      jejuni in dairy farm environmental samples.

PMID- 15992312
TI  - Characterization of Salmonella Typhimurium of animal origin obtained from the
      National Antimicrobial Resistance Monitoring System.
AB  - Salmonella Typhimurium remains one of the most common causes of salmonellosis in
      animals and humans in the United States. The emergence of multi-drug resistant
      Salmonella reduces the therapeutic options in cases of invasive infections, and
      has been shown to be associated with an increased burden of illness. In this
      study, 588 S. Typhimurium (including var. Copenhagen) isolates obtained from
      either animal diagnostic specimens (n = 199) or food animals after
      slaughter/processing (n = 389) were examined for antimicrobial susceptibility,
      presence of class-1 integrons, and characterized using pulsed-field gel
      electrophoresis and phage typing. Seventy-six percent (448/588) of isolates were
      resistant to at least one antimicrobial. Salmonella isolates displayed resistance
      most often to streptomycin (63%), tetracycline (61%), ampicillin (61%), and to a
      lesser extent, chloramphenicol (36%), ceftiofur (15%), gentamicin (9%), and
      nalidixic acid (4%), with more resistance observed among diagnostic isolates.
      Salmonella recovered from turkeys (n = 38) exhibited the highest rates of
      resistance, with 92% of isolates resistant to least one antimicrobial, and 58%
      resistant to > or =10 antimicrobials. Class 1 integrons were present in 51% of
      all isolates. Five integron associated resistance genes (aadA, aadB, pse-1, oxa-2
      and dhfr) were identified. A total of 311 PFGE patterns were generated using
      XbaI, indicating a genetically diverse population. The largest PFGE cluster
      contained 146 isolates, including DT104 isolates obtained from all seven animal
      species. Results demonstrated a varied spectrum of antimicrobial resistance,
      including several multidrug resistant clonal groups, among S. Typhimurium and S.
      Typhimurium var. Copenhagen isolates recovered from both diagnostic and
      slaughter/processing samples.

PMID- 15992313
TI  - Further characterization of Campylobacter isolated from U.S. dairy cows.
AB  - The objective of the present study was to compare polymerase chain reaction (PCR)
      identification with ribotype results and to use pulsed field electrophoresis
      (PFGE) to correlate genotypic patterns with antibiotic resistance of
      Campylobacter isolated from lactating dairy cows in the United States. Thirty
      isolates were studied. Twenty-seven of the isolates were identified by PCR as
      Campylobacter jejuni and three were identified as Campylobacter coli. Genotypic
      patterns of 15 isolates were determined by PFGE, and although isolates originated
      from geographically separated regions of the United States, some were
      genotypically identical. In contrast to their genetic similarity, antibiotic
      sensitivity patterns differed within some genotypes. Under the conditions of our
      study, we concluded that ribotyping is not as discriminatory as PCR for
      speciation, and that a phenotypic trait such as antimicrobial resistance cannot
      always be predicted within the same genotype.

PMID- 15992314
TI  - What can Busselton population health surveys tell us about asthma in older
      people?
AB  - WHAT WE NEED TO KNOW: Do the characteristics of asthma differ in people older
      than 55 years compared with younger people with respect to risk factors (atopy,
      airway hyper-responsiveness and genetic variation), smoking, lung function and
      other illness? How do inflammation and remodelling of airways vary with age and
      with duration and severity of asthma? WHAT WE NEED TO DO: Continue collecting
      prevalence data for asthma and its risk factors. Assess (i) period and cohort
      effects on asthma and its risk factors and (ii) interactions between age,
      smoking, severity and duration of asthma, lung function and airway
      responsiveness, and other concurrent disease. Measure airway responsiveness and
      exhaled nitric oxide to detect airway abnormalities in older people and relate
      this to the diagnoses of asthma and other diseases.

PMID- 15992315
TI  - Undiagnosed asthma in older people: an underestimated problem.
AB  - WHAT WE NEED TO KNOW: Are older people with respiratory symptoms aware this could
      be asthma? Which explanations for undiagnosed asthma apply most commonly in older
      Australians with asthma? Can we improve awareness of asthma in older people with
      undiagnosed asthma? Is the possibility of asthma in older people firmly
      established on the general practitioners' radar screen? What reasons most often
      determine whether GPs perform spirometry in their practice? WHAT WE NEED TO DO:
      Conduct a representative population study to assess whether older Australians
      recognise respiratory symptoms as being asthma and are reporting these symptoms.
      Conduct and evaluate a pilot asthma health promotion program for older people.
      Conduct a controlled therapeutic trial of people with undiagnosed asthma to
      assess treatment benefits and produce treatment recommendations. Identify whether
      the prominence of asthma in older people can be brought to the attention of GPs.
      Analyse more carefully the issues associated with innovation of office
      spirometry.

PMID- 15992316
TI  - Respiratory symptoms and lung function in older people with asthma or chronic
      obstructive pulmonary disease.
AB  - WHAT WE NEED TO KNOW: What is an agreed definition of chronic obstructive
      pulmonary disease (COPD) for epidemiological research? What are the predicted
      values of gas transfer (TLCO) for Australian populations? What is the prevalence
      of asthma and COPD in people over the age of 70? How does the prevalence of
      asthma and COPD in Australia compare with that in other countries? WHAT WE NEED
      TO DO: Conduct community-based studies examining the burden of illness due to
      obstructive lung disease, using a common protocol that allows international
      comparisons of data.

PMID- 15992317
TI  - Understanding asthma in older Australians: a qualitative approach.
AB  - WHAT WE NEED TO KNOW: Are there differences in symptom interpretation in older
      people with asthma? What are effective drug delivery strategies in older people
      to maximise adherence and minimise side effects? How do older people with asthma
      manage their asthma? Are self-management strategies as appropriate as they are in
      younger age groups? Do older people with asthma take appropriate steps in an
      emergency? Do they own or act on asthma action plans? WHAT WE NEED TO DO:
      Identify the specific barriers that prevent the optimal care of older people with
      asthma. Address systematic barriers, such as cost and immobility, that reduce
      access to effective treatments. Ensure older people with asthma receive
      appropriate asthma treatment. Explore asthma self-management strategies in older
      people to develop effective algorithms. Educate health professionals to provide
      optimal asthma treatments and deliver appropriate education designed specifically
      for older people.

PMID- 15992318
TI  - Normal ageing of the lung: implications for diagnosis and monitoring of asthma in
      older people.
AB  - WHAT WE NEED TO KNOW: Is there an increased loss of elastic recoil over and above
      that due to ageing alone? How do we interpret inflammatory changes in the light
      of age-related airway inflammation? Is there an interaction between perception of
      airway narrowing and severity or control of disease? Are symptom-based action
      plans appropriate? Is control of the disease affected by the distribution of
      inhaled therapeutic aerosols and dry powder particles? WHAT WE NEED TO DO:
      Include patients aged 80 years and over in clinical trials. Assess functional and
      inflammatory parameters with appropriate age-matched controls in clinical trials.
      Assess feasibility and efficacy of symptom-based action plans versus those based
      on objective monitoring. Assess the responsiveness of elderly people to currently
      recommended therapies.

PMID- 15992319
TI  - How do the psychosocial consequences of ageing affect asthma management?
AB  - WHAT WE NEED TO KNOW: How do social, physical and psychological factors affect
      asthma and asthma management in older people? How can we minimise their impact
      and enhance quality of life for older people with asthma? Does inequity based on
      age, sex, socioeconomic status and/or area of residence affect accessibility,
      quality and effectiveness of care for older people with asthma? What is the
      extent of undiagnosed and undertreated asthma among older people, and what are
      the barriers to symptom reporting, diagnosis and treatment? WHAT WE NEED TO DO:
      Promote equity of access to diagnosis, investigation and treatment across age,
      sociodemographic and geographic groups. Encourage older people to seek help for
      symptoms and exacerbations. Encourage quality use of medicines among older people
      with asthma and comorbid conditions and disabilities. Promote healthy behaviours
      for older people with asthma (eg, smoking cessation, exercise, vaccination,
      better nutrition). Develop guidelines that account for complexities of older age
      and that are framed to achieve optimal quality of life for people with asthma.

PMID- 15992320
TI  - Inflammation and remodelling in the ageing airway.
AB  - WHAT WE NEED TO KNOW: What changes occur in atopic and non-atopic airway
      inflammation in asthma with increasing age? What is the relationship between
      wound healing and airway remodelling in older subjects? What is the response to
      anti-inflammatory therapy in older subjects? What is the basis of the "overlap
      syndrome" with chronic obstructive pulmonary disease in older people with asthma,
      in whom smoking contributes to airway disease? WHAT WE NEED TO DO: Identify the
      contribution of immunological mechanisms to asthma in ageing. Determine the
      extent to which airway remodelling plays a role in airflow obstruction in older
      people, specifically reversible components. Reduce the impact of smoking in young
      people with asthma.

PMID- 15992321
TI  - Distinguishing asthma and chronic obstructive pulmonary disease: why, why not and
      how?
AB  - WHAT WE NEED TO KNOW: What are the essential differences in the inflammatory
      process that lead to different pathological outcomes in asthma and chronic
      obstructive pulmonary disease (COPD)? What factors cause some patients with
      asthma to have clinical features indistinguishable from COPD, and should these
      patients be treated differently from those with early-onset, atopic asthma? What
      should be added to FEV(1) improvement after bronchodilator to enhance the ability
      of spirometry to distinguish between asthma and COPD? Why is disturbed gas
      exchange characteristic of stable COPD but rare in asthma? Why and when does COPD
      become a systemic disease with multiorgan dysfunction, while asthma generally
      does not? Does the response to bronchodilators in asthma and COPD predict
      prognosis and response to other interventions? Do people with asthma (airway
      obstruction, hyper-responsiveness and atopy) and COPD (fixed airflow limitation)
      have different natural histories, responses to treatment and prognoses? WHAT WE
      NEED TO DO: Evaluate new diagnostic tools (eg, indirect markers of inflammation)
      for asthma and COPD. Target older people in epidemiological studies to identify
      and describe the extent of asthma. Initiate community awareness programs to help
      older people with dyspnoea recognise they may have symptoms of asthma or COPD
      that should be assessed by a doctor. Define the clinical and physiological
      features of asthma and COPD in older people that indicate when and which
      treatments will achieve maximum benefit with least harm. Develop strategies for
      better, patient-focused care of people with severe airway disease, concentrating
      on device use, action plans, side effects, end-of-life decisions, exercise and
      independence in activities of daily living. Maintain research into new drugs and
      targets for preventing progressive loss of lung function in asthma and COPD.

PMID- 15992322
TI  - An algorithmic approach to diagnosing asthma in older patients in general
      practice.
AB  - WHAT WE NEED TO KNOW: How effective would an algorithm be in helping general
      practitioners diagnose asthma? What proportion of older people with undiagnosed
      asthma fail to recognise symptoms? What proportion of the population believe
      asthma does not occur in the older population? What systems or supports do GPs
      need to diagnose asthma more effectively? WHAT WE NEED TO DO: Work on developing
      a gold standard for asthma diagnosis. Develop prototype algorithms for general
      practice discussion. Conduct a general practice study to assess the effectiveness
      of an algorithm. In conjunction with GPs, develop a pilot program to increase
      awareness of the current asthma problem. Conduct focus-group research to identify
      why some people do not believe they can develop asthma for the first time in
      adult life. Conduct focus-group research to identify why some adults do not
      attribute asthma symptoms to asthma. Conduct focus groups with GPs to identify
      what support is needed to diagnose asthma more effectively. Consult with all
      stakeholders before an intervention is used. Evaluate any interventions used.

PMID- 15992324
TI  - How is the diagnosis of asthma in older people established in clinical practice?
AB  - WHAT WE NEED TO KNOW: How is breathlessness perceived and defined in older
      people? What impact does breathlessness have on quality of life? Can history
      taking and physical examination be tailored to efficiently cover all the organ
      systems associated with breathlessness? Can a self- or carer-rated questionnaire
      be used to identify asthma in patients with breathlessness? WHAT WE NEED TO DO:
      Develop self- and carer-rated questionnaires that measure change in function and
      quality of life before and after treatment. Validate objective measures of
      physical function and airflow that are sufficiently sensitive to measure change
      with treatment. Develop a diagnostic guideline in general practice that includes
      measures of mood and cognitive function and involves carers where necessary.
      Provide rehabilitation and restorative care services.

PMID- 15992323
TI  - Asthma and older people in general practice.
AB  - WHAT WE NEED TO KNOW: Why is there undiagnosed and untreated asthma in older
      people in the community and in general practice? What patient, general
      practitioner and organisational factors contribute to this? Are current best
      practice guidelines appropriate for older people with asthma? WHAT WE NEED TO DO:
      Undertake broad community and general practice screening to identify
      characteristics of older people with undiagnosed asthma. Analyse GPs'
      perspectives and decision-making processes for older people with dyspnoea.
      Undertake targeted research in general practice, trialling decision-making
      frameworks for older patients with dyspnoea. Undertake appropriate and relevant
      community and GP awareness campaigns about the prevalence of asthma in older
      people. Analyse current best practice management of asthma, including self
      management and the Asthma 3+ Visit Plan, in older people.

PMID- 15992325
TI  - Is the pharmacology of corticosteroids in the lung modified by age?
AB  - WHAT WE NEED TO KNOW: Is the lung in older patients with asthma less responsive
      to inhaled and systemic corticosteroids? (While anecdotal observations suggest
      this may be the case, no well conducted studies document the phenomenon.) WHAT WE
      NEED TO DO: Carefully plan a clinical study to compare corticosteroid
      responsiveness between older people with asthma and their younger counterparts.
      Select sensitive and clinically relevant outcome variables for this study.

PMID- 15992327
TI  - School canteens: using ripples to create a wave of healthy eating.

PMID- 15992326
TI  - Megadose therapy for vitamin D deficiency.

PMID- 15992328
TI  - The Australian Clinical Trial Registry.

PMID- 15992329
TI  - An expanding vista: bioethics from public health, indigenous and feminist
      perspectives.

PMID- 15992330
TI  - Annual intramuscular injection of a megadose of cholecalciferol for treatment of
      vitamin D deficiency: efficacy and safety data.
AB  - AIM: To evaluate the efficacy and safety of an annual intramuscular injection of
      cholecalciferol for vitamin D deficiency. DESIGN: Prospective open-label study.
      PARTICIPANTS: Five men and 45 women (mean age 66.3 years) with vitamin D
      deficiency who were given a single therapeutic intramuscular injection of 600 000
      IU (15 mg) cholecalciferol (vitamin D(3)). OUTCOME MEASURES: Serum levels of
      calcium, creatinine, 25-hydroxyvitamin D(3) (25OHD(3)) and parathyroid hormone,
      as well as early morning 2-hour urine calcium/creatinine excretion index.
      Specimens were collected at baseline and after 4 and 12 months of therapy. Data
      are reported as mean +/- 1 SD. RESULTS: Vitamin D deficiency was severe (< 12.5
      nmol/L) in one participant, moderate (12.5-24 nmol/L) in 14, and mild (25-49
      nmol/L) in 35. Twenty-four participants (48%) had secondary hyperparathyroidism.
      Following intramuscular cholecalciferol injection, serum 25OHD(3) levels
      normalised in all participants and remained above 50 nmol/L throughout the study.
      Serum 25OHD(3) levels were significantly higher at 4 months (114 +/- 35 nmol/L),
      and 12 months (73 +/- 13 nmol/L) compared with baseline (32 +/- 8 nmol/L) (P <
      0.001), increasing by an average of 128% over the 12 months. There was a
      corresponding decrease in serum parathyroid hormone levels at 4 months (6 +/- 3
      pmol/L) and at 12 months (5.2 +/- 3 pmol/L), with a 30% decrease at 12 months
      from baseline (7.4 +/- 4 pmol/L) (P < 0.01). Primary hyperparathyroidism was
      unmasked in one participant at 4 months and mild hypercalcaemia (serum calcium, <
      2.70 mmol/L) was noted in two participants (4%) at 12 months. Serum creatinine
      levels remained normal in all participants throughout the study, while increases
      in 2-hour urine calcium/creatinine excretion index were seen in 10 participants
      (20%) at 12 months, three of whom had had elevated values at baseline.
      CONCLUSIONS: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is
      effective therapy for vitamin D deficiency. While this therapy appears to be
      safe, the potential for developing hypercalciuria needs to be examined in a large
      randomised controlled trial.

PMID- 15992331
TI  - Short-term impact of smoking cessation on myocardial infarction and stroke
      hospitalisations and costs in Australia.
AB  - OBJECTIVE: To estimate the short-term benefits of a reduction in smoking on acute
      myocardial infarction (AMI) and stroke hospitalisations and costs. DESIGN AND
      SETTING: Epidemiological study which applied functions describing reductions over
      time in risk of AMI and stroke in people quitting smoking to hospitalisation
      rates and costs for Australia. MAIN OUTCOME MEASURES: The numbers of AMI and
      stroke hospitalisations in 35-64-year-olds and the associated costs that could
      have been avoided over a 7-year period from 2001-02 if smoking prevalence had
      decreased by 1% in the first year (Scenario 1) or by 1% per annum for 5
      consecutive years (Scenario 2). RESULTS: Under Scenario 1, almost 1000
      hospitalisations for AMI and about 350 hospitalisations for stroke would have
      been avoided over 7 years, saving about $20.4 million in health care costs. Under
      Scenario 2, over 3000 AMI hospitalisations and over 1000 stroke hospitalisations
      would be avoided, and health care costs could be reduced by $61.6 million (2.75%
      of costs for AMI and stroke over the period). CONCLUSIONS: This study provides
      further support for the proposition that modest and achievable reductions in
      smoking rates can substantially improve health outcomes and reduce health care
      costs, even in the short term.

PMID- 15992332
TI  - Recognition of depression and psychosis by young Australians and their beliefs
      about treatment.
AB  - OBJECTIVES: To assess young people's ability to recognise clinically defined
      depression and psychosis, the types of help they thought appropriate for these
      problems, their knowledge of appropriate treatments, and their perceptions
      regarding prognosis. DESIGN: A cross-sectional telephone survey using structured
      interviews. Vignettes of a person with either depression or psychosis were
      presented, followed by questions related to recognition of the disorder, best
      forms of treatment and the prognosis. PARTICIPANTS: A randomly selected sample of
      1207 young people aged 12-25 years. SETTING: Melbourne, Victoria, and surrounding
      regional and rural areas. OUTCOME MEASURES: Responses to a mental health literacy
      questionnaire. RESULTS: Almost half the respondents were able to identify
      depression correctly, whereas only a quarter identified psychosis correctly.
      Counsellors and family or friends were the most commonly cited forms of best
      help, with family or friends preferred by the younger age group for depression.
      General practitioners were considered more helpful for depression, and
      psychiatrists and psychologists more helpful for psychosis. Most respondents
      considered counselling and psychotherapy to be helpful. However, more than half
      the respondents expressed negative or equivocal views regarding the helpfulness
      of recommended pharmacological treatments. CONCLUSIONS: The limitations we
      identified in youth mental health literacy may contribute to the low rates of
      treatment and the long duration of untreated illness reported in other studies.
      There is a need for initiatives to enhance mental health literacy among young
      people, and those close to them, if benefits of early treatment are to be
      realised.

PMID- 15992333
TI  - The aromatase inhibitors in early breast cancer: who, when, and why?
AB  - The aromatase inhibitors deplete oestrogen by inhibiting aromatase, the enzyme
      that synthesises oestrogen from androgens. They are effective as therapies for
      breast cancer only in postmenopausal women whose tumours express oestrogen or
      progesterone receptors. As adjuvant therapy, tamoxifen and the aromatase
      inhibitors have similar efficacy in the first 5 years of treatment. Aromatase
      inhibitors can be used as an alternative to tamoxifen in women with symptomatic
      intolerance or a contraindication to tamoxifen. Early data suggest that switching
      to an aromatase inhibitor after 2-5 years of tamoxifen therapy is beneficial in
      women with high-risk disease. Aromatase inhibitors are associated with more hot
      flushes than placebo, but with fewer hot flushes, less endometrial toxicity and
      venous thromboembolism, and more arthralgia, myalgia and bone fracture than
      tamoxifen.

PMID- 15992334
TI  - Increasing diversity at the cost of decreasing equity? Issues raised by the
      establishment of Australia's first religiously affiliated medical school.

PMID- 15992335
TI  - Accreditation of a religiously affiliated medical school.

PMID- 15992337
TI  - Teaching on the run tips 9: in-training assessment.

PMID- 15992338
TI  - Deaths associated with dengue haemorrhagic fever: the first in Australia in over
      a century.
AB  - A dengue fever epidemic was recognised in the Torres Strait Islands of Queensland
      in late 2003. Two fatal cases of dengue haemorrhagic fever occurred in early
      2004. This severe manifestation is more common when a patient is infected a
      second time, with a different virus serotype to the first infection. These are
      the first fatalities related to dengue fever in Australia in over a century.

PMID- 15992339
TI  - A culture of ill health: public health or Aboriginality?

PMID- 15992341
TI  - 12. Assessment of developmental learning and behavioural problems in children and
      young people.
AB  - Brain development from late pregnancy to 3 years of age affects a child's
      learning, behaviour and health throughout life. Behavioural difficulties in
      children are usually symptoms of underlying problems. Observing a child's
      appearance and performance, and taking a detailed history (considering factors in
      the child, the home, the school and the wider environment) provide most of the
      information needed for diagnosing behavioural problems. It is important to know
      what is "normal" for all stages of a child's development, but equally important
      not to confuse behavioural difficulties with normal variations and behaviours
      associated with developmental stages. Assessment and early intervention for
      behavioural and learning difficulties in children require a multidisciplinary
      team approach. As well as the recommended "multimodal" approach for managing
      attention deficit hyperactivity disorder, shared care with a general practitioner
      is available in some states, but medication is likely to be the trigger for a
      positive outcome.

PMID- 15992342
TI  - Incidental finding of Dracunculus medinensis in Australia.

PMID- 15992343
TI  - Tungiasis in recently arrived African refugees.

PMID- 15992344
TI  - Vitamin D and adult bone health in Australia and New Zealand: a position
      statement.

PMID- 15992345
TI  - Outcome of overseas commercial kidney transplantation: an Australian perspective.

PMID- 15992346
TI  - Detention for tuberculosis: public health and the law.

PMID- 15992347
TI  - The shortage of kidneys for transplantation in Australia.

PMID- 15992348
TI  - A nationwide perspective on asthma in older Australians.
AB  - WHAT WE NEED TO KNOW: What is the prevalence of impaired lung function among
      older people in Australia? How can we differentiate between asthma and other
      causes of breathlessness in population-based health surveys of older people? What
      are the effects of ageing on people with asthma? WHAT WE NEED TO DO: Improve
      existing survey measures and accuracy of diagnosis. Incorporate measures of
      spirometric function into health surveys of representative samples of the general
      population. Use spirometry in the diagnostic work-up of older patients with
      dyspnoea.

PMID- 15992349
TI  - DNA helicases as targets for anti-cancer drugs.
AB  - DNA helicases have essential roles in nucleic acid metabolism by facilitating
      cellular processes including replication, recombination, DNA repair, and
      transcription. The vital roles of helicases in these pathways are reflected by
      their emerging importance in the maintenance of genomic stability. Recently, a
      number of human diseases with cancer predisposition have been shown to be
      genetically linked to a specific helicase defect. This has led researchers to
      further investigate the roles of helicases in cancer biology, and to study the
      efficacy of targeting human DNA helicases for anti-cancer drug treatment.
      Helicase-specific inhibition in malignant cells may compromise the high
      proliferation rates of cancerous tissues. The role of RecQ helicases in response
      to replicational stress suggests a molecular target for selectively eliminating
      malignant tumor cells by a cancer chemotherapeutic agent. Alternate DNA secondary
      structures such as G-quadruplexes that may form in regulatory regions of
      oncogenes or G-rich telomere sequences are potential targets for cancer therapy
      since these sequence-specific structures are proposed to affect gene expression
      and telomerase activation, respectively. Small molecule inhibitors of G
      quadruplex helicases may be used to regulate cell cycle progression by modulating
      promotor activation or disrupting telomere maintenance, important processes of
      cellular transformation. The design of small molecules which deter helicase
      function at telomeres may provide a molecular target since telomerase activity is
      necessary for the proliferation of numerous immortal cells. Although evidence
      suggests that helicases are specifically inhibited by certain DNA binding
      compounds, another area of promise in anti-cancer therapy is siRNA technology.
      Specific knockdown of helicase expression can be utilized as a means to sensitize
      oncogenic proliferating cell lines. This review will address these topics in
      detail and summarize the current avenues of research in anti-cancer therapy
      targeting helicases through small molecule inhibitors of DNA-protein complexes,
      DNA binding drugs, or down-regulation of helicase gene expression.

PMID- 15992350
TI  - Prospects for plant-derived chemopreventive agents exhibiting multiple mechanisms
      of action.
AB  - There is great potential for the use of plant-derived agents in the fight to
      prevent onset or delay progression of the carcinogenic process. Epidemiological
      evidence for their chemopreventive action is compelling, but even though many of
      these compounds have an extensive history of use within the human populace, it is
      of increasing importance to determine more precisely the primary targets
      contributing to their efficacy, prior to embarking on large-scale clinical
      trials. This rapidly moving field now concentrates in particular, on the
      modulating effects these agents can have on cellular signalling pathways involved
      in the apoptotic, proliferative and angiogenic processes, perturbances to which,
      are common in many cancers. It is perhaps the ability of these agents to exhibit
      multi-site mechanisms of action that offers their key to success where
      conventional single-site agents have disappointed in the past. As well as being
      promising chemopreventive agents, there is also an exciting role for these
      compounds in combinatorial therapy with more traditional chemotherapeutics,
      potentially in lowering of toxicity and enhancing efficacy for treatment of more
      advanced cancers. This review will summarise known and proposed mechanisms of
      action for various chemopreventive agents of interest highlighting their
      potential in combination therapy, and will address benefits and problems of using
      such multi-site agents in long-term prevention/therapeutic regimes.

PMID- 15992351
TI  - Synthesis and biological activity of new class of dioxygenated anticancer agents.
AB  - This paper describes extensive research on the activity of more of 100 cytotoxic
      compounds containing an oxygenated ring in their structure and isolated from
      natural plants or prepared by semisynthesis or synthesis from available
      intermediates. Anticancer drugs have been classified according to the chemical
      structure of the natural products that are considered to lead the series. The
      origin and mechanism of action involved in each case have been considered. This
      new family of natural, semisynthetic and synthetic products includes compounds
      with interesting antitumor activity such as podophyllotoxin derivatives, NK-611
      (15), TOP-53 (16), NPF (24) and Tafluposide (28); camptothecin analogs such as 45
      with a considerable cytotoxicity against beta-cell chronic lymphocytic leukemia
      (CLL), and 52 (new piperazinyl-CPT analog). New dioxygenated ellipticine analogs
      showed more activity and stability than the natural pattern when the structure
      incorporated a lactone function instead of the pyridine ring. In the acridine
      series the new tetracyclic derivatives 75 and 76 containing ethylenedioxy groups
      at the 2- and 3-positions of the acridine system exhibited the same activity as m
      AMSA in vivo against murine P-388 leukemia. Other isolated compounds containing a
      dioxygenated ring in their structure such as 100 and 101 showed antitumor
      activities related to kinase inhibition, and are attractive candidates for
      development of new synthetic antitumor agents.

PMID- 15992352
TI  - Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular
      mechanisms.
AB  - Sesquiterpene lactones (SLs) are the active constituents of a variety of
      medicinal plants used in traditional medicine for the treatment of inflammatory
      diseases. In recent years, the anti-cancer property of various SLs has attracted
      a great deal of interest and extensive research work has been carried out to
      characterize the anti-cancer activity, the molecular mechanisms, and the
      potential chemopreventive and chemotherapeutic application of SLs. In this
      review, we attempt to summarize the current knowledge of the anti-cancer
      properties of SLs by focusing on the following important issues. First, we
      discuss the structure-activity relationship of SLs. All SLs contain a common
      functional structure, an alpha-methylene-gamma-lactone group, and this important
      chemical characteristic means that the thiol-reactivity of SLs is an underlying
      mechanism responsible for their bioactivities. Second, we assess the experimental
      evidence for the anti-cancer function of SLs obtained from both in vitro cell
      culture and in vivo animal models. Various SLs have been demonstrated to execute
      their anti-cancer capability via inhibition of inflammatory responses, prevention
      of metastasis and induction of apoptosis. Thirdly, we outline the molecular
      mechanisms involved in the anti-cancer activity of SLs, in particular, the SL
      thiols reaction, the effect of SLs on cell signaling pathways such as nuclear
      transcription factor-kappaB (NF-kappaB) and mitogen-activated protein kinases
      (MAPK). Finally, we recapitulate some important SLs with regards to their anti
      cancer activities and their potential in anti-cancer drug development. Taken
      together, many SLs are emerging as promising anti-cancer agents with potential
      applications in both cancer chemotherapy and chemoprevention.

PMID- 15992353
TI  - Cisplatin is a DNA-damaging antitumour compound triggering multifactorial
      biochemical responses in cancer cells: importance of apoptotic pathways.
AB  - cis-diamminedichloroplatinum(II) (cisplatin) is among the most active antitumour
      agent used in human chemotherapy. The purpose of this review is to give an
      insight in several molecular mechanisms that mediate the sensitivity of cancer
      cells to this drug and to show how recent progress in our knowledge on some
      critical molecular events should lay the foundations of a more rational approach
      to anticancer drug design. Cisplatin is primarily considered as a DNA-damaging
      anticancer drug, mainly forming different types of bifunctional adducts in its
      reaction with cellular DNA. We will address the question of cellular activity
      disruption that cisplatin could cause through binding to more sensitive region of
      the genome such as telomeres. Cellular mechanisms of resistance to cisplatin are
      multifactorial and contribute to severe limitation in the use of this drug in
      clinics. They include molecular events modulating the amount of drug-DNA
      interaction, such as a reduction in cisplatin accumulation inside cancer cells or
      inactivation of cisplatin by thiol-containing species. Other important mechanisms
      acting downstream to the initial reaction of cisplatin with DNA, include an
      increase in adducts repair and a decrease in induction of apoptosis. Recently
      accumulating evidence suggest a role of the long patch DNA mismatch repair system
      in sensing cisplatin-damaged DNA and in triggering cell death through a c-Abl-
      and p73-dependent cascade; two other important pathways have been unravelled that
      are the mitogen-activated protein kinase cascade and the tumor suppressor p53.
      Several of these mechanisms underlying cisplatin resistance have been exploited
      to design new platinum derivatives. This issue will be covered in the present
      review.

PMID- 15992354
TI  - Multi-nuclear platinum drugs: a new paradigm in chemotherapy.
AB  - The initial report of the therapeutic anticancer properties of a di-nuclear
      platinum complex in 1988 started a new paradigm in platinum based chemotherapy.
      Several multi-nuclear platinum complexes have entered clinical trials in recent
      years, with varying results. This group of charged complexes, consisting of di-
      and tri-nuclear compounds linked by aliphatic ligands, many with hydrogen bonding
      functionality, are able to overcome cisplatin and carboplatin resistance in many
      important human cancer cell lines. The adducts they form with DNA--which are, to
      some extent, affected by their pre-covalent association--are the reason for their
      increased cytotoxicity, and are distinctly different from those formed by
      cisplatin. Multi-nuclear platinum DNA adducts are broadly defined as flexible,
      non-directional and mainly interstrand cross-links. These complexes are also able
      to induce conformational changes in DNA, particularly the conversion from B-type
      to Z- and A-type. While these complexes are much more cytotoxic than cisplatin,
      they are also highly toxic. The maximum tolerated doses range from 0.006 to 1.1
      mg/m(2) which is 10 to 100 fold lower than cisplatin. BBR3464 has shown in vivo
      activity at its MTD in several pre-clinical and clinical trials; however, recent
      phase II trials have shown that BBR3464, and other multi-nuclear platinum drugs,
      did not yield results substantially different from cisplatin, possibly due to
      their binding and degradation by human plasma proteins. This review will look at
      the success, and limitations, of multi-nuclear platinum drugs, and discuss their
      future potential as anti-cancer agents.

PMID- 15992355
TI  - Progress in the development of aminopeptidase N (APN/CD13) inhibitors.
AB  - Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family
      involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly)
      from N-terminal of bioactive peptides and amide or arylamide derivatives of amino
      acids. The expression of APN being up regulated has been implicated in the
      pathogenesis of a variety of diseases such as cancer, leukemia, diabetic
      nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected
      to be useful for the treatment of these disorders. This article reviews briefly
      the structure characteristic and possible function of APN. The proposed
      biomolecular structures and mechanism of action used in the design of APNIs are
      thoroughly covered. Major emphasis is on recently published potent, small
      molecular weight APNIs and their essential structure activity relationship (SAR).
      Finally, available clinical results of compounds in development are summarized in
      this review.

PMID- 15992356
TI  - Lanthanide bearing microparticulate systems for multi-modality imaging and
      targeted therapy of cancer.
AB  - The rapid developments of high-resolution imaging techniques are offering unique
      possibilities for the guidance and follow up of recently developed sophisticated
      anticancer therapies. Advanced biodegradable drug delivery systems, e.g. based on
      liposomes and polymeric nanoparticles or microparticles, are very effective tools
      to carry these anticancer agents to their site of action. Elements from the group
      of lanthanides have very interesting physical characteristics for imaging
      applications and are the ideal candidates to be co-loaded either in their non
      radioactive or radioactive form into these advanced drug delivery systems because
      of the following reasons: Firstly, they can be used both as magnetic resonance
      imaging (MRI) and computed tomography (CT) contrast agents and for single photon
      emission computed tomography (SPECT). Secondly, they can be used for radionuclide
      therapies which, importantly, can be monitored with SPECT, CT, and MRI. Thirdly,
      they have a relatively low toxicity, especially when they are complexed to
      ligands. This review gives a survey of the currently developed lanthanide-loaded
      microparticulate systems that are under investigation for cancer imaging and/or
      cancer therapy.

PMID- 15992357
TI  - A general one-step method for the cloning of PCR products.
AB  - A very fast, highly efficient, versatile and low-cost cloning of PCR products is
      described. PCR amplicons, obtained with any set of primers, is directly
      integrated into circular plasmid vectors by means of a one-step restriction
      ligation procedure. When using proof-reading DNA polymerases, 100% cloning
      efficiency is easily achieved, implying that direct cloning into 'final-use'
      vectors (i.e. avoiding any intermediate cloning step) is a feasible task. Albeit
      with a lower efficiency, the same procedure is also suitable for the cloning of
      PCR products generated by 'non-proof-reading' DNA polymerases. Furthermore, with
      a simple modification of the vector polylinker site, the present method can be
      easily adapted to the directional cloning of open-reading-frame-encoding
      amplicons. This one-step procedure thus couples high efficiency with high
      reliability and versatility, and lends itself as the method of choice for routine
      cloning of PCR products.

PMID- 15992359
TI  - Investigating the allosterism of acyl-CoA:cholesterol acyltransferase (ACAT) by
      using various sterols: in vitro and intact cell studies.
AB  - ACAT1 (acyl-CoA:cholesterol acyltransferase 1) is thought to have two distinct
      sterol-binding sites: a substrate-binding site and an allosteric-activator site.
      In the present work, we investigated the structural features of various sterols
      as substrates and/or activators in vitro. The results show that without
      cholesterol, the plant sterol sitosterol is a poor substrate for ACAT. In the
      presence of cholesterol, ACAT1-mediated esterification of sitosterol is highly
      activated while ACAT2-mediated esterification of sitosterol is only moderately
      activated. For ACAT1, we show that the stereochemistry of the 3-hydroxy group at
      steroid ring A is a critical structural feature for a sterol to serve as a
      substrate, but less critical for activation. Additionally, enantiomeric
      cholesterol, which has the same biophysical properties as cholesterol in
      membranes, fails to activate ACAT1. Thus ACAT1 activation by cholesterol is the
      result of stereo-specific interactions between cholesterol and ACAT1, and is not
      related to the biophysical properties of phospholipid membranes. To demonstrate
      the relevance of the ACAT1 allosteric model in intact cells, we showed that
      sitosterol esterification in human macrophages is activated upon cholesterol
      loading. We further show that the activation is not due to an increase in ACAT1
      protein content, but is partly due to an increase in the cholesterol content in
      the endoplasmic reticulum where ACAT1 resides. Together, our results support the
      existence of a distinct sterol-activator site in addition to the sterol-substrate
      site of ACAT1 and demonstrate the applicability of the ACAT1 allosteric model in
      intact cells.

PMID- 15992360
TI  - Fetal programming of appetite by exposure to a maternal low-protein diet in the
      rat.
AB  - Undernutrition in fetal life programmes risk of obesity and the metabolic
      syndrome in adult life. Rat studies indicate that exposure to a maternal low
      protein diet throughout fetal life establishes a preference for high-fat foods.
      The present study aimed to assess the effect of low protein exposure during
      discrete 7-day periods of gestation upon feeding behaviour (full gestation 22
      days). Pregnant rats were fed control or low-protein diet, with low-protein
      feeding targeted at day 0--7 (LP Early), day 8--14 (LP Mid) or day 15--22 (LP
      Late) of gestation. At 12 weeks of age, offspring were placed on a macronutrient
      self-selection regimen. Prenatal protein restriction programmed feeding behaviour
      in female, but not male, offspring. Among females, all low-protein exposed groups
      consumed less fat than the control group (P<0.05). Male offspring showed no
      changes in feeding behaviour. In males and females fed a low-fat chow diet, there
      were metabolic differences between the groups. LP Early and LP Late males had
      greater hepatic glycogen stores than control animals. There were no differences
      in the size of abdominal fat depots in either male or female rats exposed to low
      protein diet at any point in gestation. The data suggest that programming of
      feeding behaviour is likely to be gender-specific and dependent upon the timing
      of nutrient insult in fetal life. This work may have implications for the
      development of the metabolic syndrome.

PMID- 15992358
TI  - A short guided tour through functional and structural features of saposin-like
      proteins.
AB  - SAPLIPs (saposin-like proteins) are a diverse family of lipid-interacting
      proteins that have various and only partly understood, but nevertheless
      essential, cellular functions. Their existence is conserved in phylogenetically
      most distant organisms, such as primitive protozoa and mammals. Owing to their
      remarkable sequence variability, a common mechanism for their actions is not
      known. Some shared principles beyond their diversity have become evident by
      analysis of known three-dimensional structures. Whereas lipid interaction is the
      basis for their functions, the special cellular tasks are often defined by
      interaction partners other than lipids. Based on recent findings, this review
      summarizes phylogenetic relations, function and structural features of the
      members of this family.

PMID- 15992362
TI  - Integration of G protein signals by extracellular signal-regulated protein
      kinases in SK-N-MC neuroepithelioma cells.
AB  - Mammalian cells often receive multiple extracellular stimuli under physiological
      conditions, and the various signaling inputs have to be integrated for the
      processing of complex biological responses. G protein-coupled receptors (GPCRs)
      are critical players in converting extracellular stimuli into intracellular
      signals. In this report, we examined the integration of different GPCR signals by
      mitogen-activated protein kinases (MAPKs) using the SK-N-MC human brain
      neuroepithelioma cells as a neuronal model. Stimulation of the Gi-coupled
      neuropeptide Y1 and Gq-coupled muscarinic M1 acetylcholine receptors, but not the
      Gs-coupled dopamine D1 receptor, led to the activation of extracellular signal
      regulated kinase (ERK). All three receptors were also capable of stimulating c
      Jun NH2-terminal kinases (JNK) and p38 MAPK. The Gi-mediated ERK activation was
      completely suppressed upon inhibition of Src tyrosine kinases by PP1, while the
      Gq-induced response was suppressed by both PP1 and the Ca2+ chelator, BAPTA-AM.
      In contrast, activations of JNK and p38 by Gs-, Gi-, and Gq-coupled receptors
      were sensitive to PP1 and BAPTA-AM pretreatments. Simultaneous stimulation of Gi-
      and Gq-coupled receptors resulted in the synergistic activation of ERK, but not
      JNK or p38 MAPK. The Gi/Gq-induced synergistic ERK activation was PTX-sensitive,
      and appeared to be a co-operative effect between Ca2+ and Src family tyrosine
      kinases. Enhanced ERK activation was associated with an increase in CREB
      phosphorylation, while the JNK and p38-responsive transcription factor ATF-2 was
      weakly enhanced upon Gi/Gq-induction. This report provides evidence that G
      protein signals can be integrated at the level of MAPK, resulting in differential
      effects on ERK, JNK and p38 MAPK in SK-N-MC cells.

PMID- 15992363
TI  - Activation of latent cyclin-dependent kinase 5 (Cdk5)-p35 complexes by membrane
      dissociation.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase of increasingly recognized
      importance in a large number of fields, ranging from neuronal migration to
      synaptic plasticity and neurodegeneration. However, little is known about its
      mechanism of activation beyond its requirement for binding to p35 or p39. We have
      examined membrane interactions as one method of regulating the Cdk5-p35 complex.
      The kinase activity of Cdk5-p35 is low when it is bound to membranes. The Cdk5
      p35 found in rat brain extract associates with membranes in two ways.
      Approximately 75% of complexes associate with membranes via ionic interactions
      only, and the remaining 25% associate with membranes via ionic interactions
      together with lipidic interactions. Solubilization with detergent or high-salt
      solution activates Cdk5-p35 several fold, and this activation is reversible.
      Therefore, membrane interactions represent a novel mechanism for the regulation
      of Cdk5-p35 kinase activity.

PMID- 15992364
TI  - Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask
      novel modulation of dopamine transporters by amphetamine.
AB  - Insulin affects brain reward pathways and there is converging evidence that this
      occurs through insulin regulation of the dopamine (DA) transporter (DAT). In rats
      made hypoinsulinemic by fasting, synaptosomal DA uptake is reduced.
      Interestingly, [3H]DA uptake is increased in hypoinsulinemic rats with a history
      of amphetamine self-administration. The possibility that amphetamine and insulin
      act in concert to regulate DAT activity prompted this study. Here we show that
      [3H]DA uptake, measured in vitro and clearance of exogenously applied DA in vivo,
      is significantly reduced in rats made hypoinsulinemic by a single injection of
      streptozotocin. Strikingly, amphetamine (1.78 mg/kg, given every other day for 8
      days) restored DA clearance in streptozotocin-treated rats but was without effect
      on DA clearance in saline-treated rats. Basal locomotor activity of
      streptozotocin-treated rats was lower compared to control rats; however, in
      streptozotocin-treated rats, hyperlocomotion induced by amphetamine increased
      over successive amphetamine injections. In saline-treated rats the locomotor
      stimulant effect of amphetamine remained stable across the four amphetamine
      injections. These results provide exciting new evidence that actions of
      amphetamine on DA neurotransmission are insulin-dependent and further suggest
      that exposure to amphetamine may cause long-lasting changes in DAT function.

PMID- 15992367
TI  - Anti-CD11d antibody treatment reduces free radical formation and cell death in
      the injured spinal cord of rats.
AB  - Treatment with a monoclonal antibody (mAb) against the CD11d subunit of the
      leukocyte integrin CD11d/CD18 after spinal cord injury (SCI) decreases
      intraspinal inflammation and oxidative damage, improving neurological function in
      rats. In this study we tested whether the anti-CD11d mAb treatment reduces
      intraspinal free radical formation and cell death after SCI. Using clip
      compression SCI in rats, reactive oxygen species (ROS) generated in injured
      spinal cord were detected using 2',7'-dichlorofluorescin-diacetate and
      hydroethidine as fluorescent probes. ROS in the injured cord increased
      significantly after SCI; anti-CD11d mAb treatment significantly reduced this ROS
      formation. Immunohistochemistry and western blotting were employed to assess the
      effects of anti-CD11d mAb treatment on spinal cord expression of gp91Phox (a
      subunit of NADPH oxidase producing superoxide) on formation of 4-hydroxynonenal
      (HNE, indicating lipid peroxidation) and on expression of caspase-3. We also
      assessed effects on cell death, determined by cell morphology. The expression of
      gp91Phox, formation of HNE, and cell death increased after SCI. Anti-CD11d mAb
      treatment clearly attenuated these responses. In conclusion, anti-CD11d mAb
      treatment significantly reduces intraspinal free radical formation caused by
      infiltrating leukocytes after SCI, thereby reducing secondary cell death. These
      effects likely underlie tissue preservation and improved neurological function
      that result from the mAb treatment.

PMID- 15992368
TI  - Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W
      cells via angiotensin type 2 receptor activation.
AB  - The angiotensin type 2 (AT2) receptor has been previously demonstrated to exert
      neuroprotective actions possibly by inducing neuronal cell differentiation
      involving neurite outgrowth. The nuclear hormone receptor peroxisome proliferator
      activated receptor gamma (PPARgamma) is an important transcriptional regulator of
      cell differentiation. The aim of the present study was to clarify whether
      PPARgamma is involved in AT2-receptor-mediated morphological neuronal cell
      differentiation. To investigate AT2-receptor-mediated morphological neuronal cell
      differentiation, rat pheochromocytoma cells (PC12W cells) expressing AT2 but not
      AT1 receptors, were stimulated with angiotensin II (Ang II, 100 nmol/L) +/- the
      PPARgamma antagonists GW9662 (3 micromol/L) and bisphenol A diglycidyl ether
      (BADGE, 1 micromol/L), and neurite outgrowth of these cells was assessed. Ang II
      induced neurite outgrowth by 19 +/- 1.6-fold (p < 0.01). Antagonizing PPARgamma
      activity by GW9662 or BADGE potently blocked Ang II-induced neurite outgrowth
      (Ang II + GW9662: 6.6 +/- 1.5-fold, p < 0.05; Ang II + BADGE: 1.3 +/- 0.7-fold, p
      < 0.01). AT2 receptor activation by Ang II markedly induced mRNA and protein
      expression of the PPARgamma2 isoform and enhanced ligand-induced PPARgamma
      activity in transactivation assays. In conclusion, the present study demonstrates
      that Ang II induces PPARgamma expression and ligand-mediated PPARgamma activity
      via AT2 receptor activation, which appears to be a crucial process in AT2
      receptor mediated neurite outgrowth. AT2 receptor/PPARgamma-dependent neurite
      outgrowth may play an important role during neuroprotective processes.

PMID- 15992369
TI  - Kainic acid-induced status epilepticus alters GABA receptor subunit mRNA and
      protein expression in the developing rat hippocampus.
AB  - Kainic acid-induced status epilepticus leads to structural and functional changes
      in inhibitory GABAA receptors in the adult rat hippocampus, but whether similar
      changes occur in the developing rat is not known. We have used in situ
      hybridization to study status epilepticus-induced changes in the GABAAalpha1
      alpha5, beta1-beta3, gamma1 and gamma2 subunit mRNA expression in the hippocampus
      of 9-day-old rats during 1 week after the treatment. Immunocytochemistry was
      applied to detect the alpha1, alpha2 and beta3 subunit proteins in the control
      and treated rats. In the saline-injected control rats, the alpha1 and alpha4
      subunit mRNA expression significantly increased between the postnatal days 9-16,
      whereas those of alpha2, beta3 and gamma2 subunits decreased. The normal
      developmental changes in the expression of alpha1, alpha2, beta3 and gamma2
      subunit mRNAs were altered after the treatment. The immunostainings with
      antibodies to alpha1, alpha2 and beta3 subunits confirmed the in situ
      hybridization findings. No neuronal death was detected in any hippocampal
      subregion in the treated rats. Our results show that status epilepticus disturbs
      the normal developmental expression pattern of GABAA receptor subunit in the rat
      hippocampus during the sensitive postnatal period of brain development. These
      perturbations could result in altered functional and pharmacological properties
      of GABAA receptors.

PMID- 15992370
TI  - Differences in gene expression profile among SH-SY5Y neuroblastoma subclones with
      different neurite outgrowth responses to nerve growth factor.
AB  - Nerve growth factor (NGF) plays a key role in the differentiation of neurons. In
      this study, we established three NGF-induced neurite-positive (NIN+) subclones
      that showed high responsiveness to NGF-induced neurite outgrowth and three NGF
      induced neurite-negative (NIN-) subclones that abolished NGF-induced neurite
      outgrowth from parental SH-SY5Y cells, and analyzed differences in the NGF
      signaling cascade. The NIN+ subclones showed enhanced responsiveness to FK506
      mediated neurite outgrowth as well. To clarify the mechanism behind the high
      frequency of NGF-induced neurite outgrowth, we investigated differences in NGF
      signaling cascade among subclones. Expression levels of the NGF receptor TrkA,
      and NGF-induced increases in mRNAs for the immediate-early genes (IEGs) c-fos and
      NGF inducible (NGFI) genes NGFI-A, NGFI-B and NGFI-C, were identical among
      subclones. Microarray analysis revealed that the NIN+ cell line showed a very
      different gene expression profile to the NIN- cell line, particularly in terms of
      axonal vesicle-related genes and growth cone guidance-related genes. Thus, the
      difference in NGF signaling cascade between the NIN+ and NIN- cell lines was
      demonstrated by the difference in gene expression profile. These differentially
      expressed genes might play a key role in neurite outgrowth of SH-SY5Y cells in a
      region downstream from the site of induction of IEGs, or in a novel NGF signaling
      cascade.

PMID- 15992371
TI  - Synapse associated protein 102 is a novel binding partner to the cytoplasmic
      terminus of neurone-glial related cell adhesion molecule.
AB  - Neurone glial-related cell adhesion molecule (NrCAM) is a member of the L1 family
      of transmembrane cell adhesion receptors which are involved in the development
      and function of the mammalian nervous system. How these receptors interact with
      intracellular signalling pathways is not understood. To date the only identified
      binding partner to the cytoplasmic terminus of NrCAM is ankyrin G. We screened a
      developing rat brain cDNA yeast two-hybrid library with the cytoplasmic domain of
      NrCAM to identify further intracellular binding partners. We identified synapse
      associated protein 102 (SAP102) as a new binding partner for NrCAM. The
      interaction was confirmed biochemically using glutathione S-transferase (GST)
      pull-down and tandem affinity purification, and also immunocytochemically as
      NrCAM and SAP102 co-localized in COS-7 and cerebellar granule cells. Binding was
      specific to NrCAM as neither neurofascin nor L1 bound SAP102, and this
      interaction was reliant on the last three amino acids of NrCAM. Additionally,
      NrCAM constructs whose last three amino acids had been deleted appeared to have a
      dominant negative effect on neurite extension of cerebellar granule cells. This
      is the first interaction reported for NrCAM, and its association with SAP102
      suggests that it is part of a larger complex which can interact with many
      different signalling pathways.

PMID- 15992372
TI  - Acute anoxia induces tau dephosphorylation in rat brain slices and its possible
      underlying mechanisms.
AB  - Abnormal phosphorylation of microtubule-associated protein tau plays a critical
      role in Alzheimer's disease (AD), together with a distinct decrease of energy
      metabolism in the affected brain regions. To explore the effect of acute energy
      crisis on tau phosphorylation and the underlying mechanisms, we incubated rat
      brain slices in artificial cerebrospinal fluid (aCSF) at 37 degrees C with or
      without an oxygen supply, or in aCSF with low glucose concentrations. Then, the
      levels of total, phosphorylated and unphosphorylated tau, as well as the
      activities and levels of protein phosphatase (PP)-1, PP-2A, glycogen synthase
      kinase 3 (GSK-3), extracellular signal-regulated protein kinase (ERK) and C-jun
      amino terminal kinase (JNK), were measured. It was found, unexpectedly, that tau
      was significantly dephosphorylated at Ser396/Ser404 (PHF-1), Ser422 (R145),
      Ser199/Ser202 (Tau-1), Thr181 (AT270), Ser202/Thr205 (AT8) and Thr231 (AT180) by
      acute anoxia for 30 min or 120 min. The activity of PP-2A and the level of
      dephosphorylated PP-2A catalytic subunit at tyrosine 307 (Tyr307) were
      simultaneously increased. The active forms of ERK1/2 and JNK1/2 were decreased
      under anoxic incubation. The PP-2A inhibitor, okadaic acid (OA, 0.75 microm),
      completely prevented tau from acute anoxia-induced dephosphorylation and restored
      the active forms of ERK1/2 and JNK1/2 to the control level. The activities and
      protein levels of GSK-3 and PP-1 showed no change during acute anoxia. These data
      suggest that acute anoxia induces tau dephosphorylation, and that PP-2A may play
      a key role in tau dephosphorylation induced by acute anoxia.

PMID- 15992373
TI  - Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated
      liberation of beta-amyloid precursor protein carboxy-terminal fragment.
AB  - Cleavage of the beta-secretase processed beta-amyloid precursor protein by gamma
      secretase leads to the extracellular release of Abeta42, the more amyloidogenic
      form of the beta-amyloid peptide, which subsequently forms the amyloid-plaques
      diagnostic of Alzheimer's disease. Mutations in beta-amyloid precursor protein
      (APP), presenilin-1 and presenilin-2 associated with familial Alzheimer's disease
      (FAD) increase release of Abeta42, suggesting that FAD may directly result from
      increased gamma-secretase activity. Here, we show that familial Alzheimer's
      disease mutations clustered near the sites of gamma-secretase cleavage actually
      decrease gamma-secretase-mediated release of the intracellular fragment of APP
      (CTFgamma). Concordantly, presenilin-1 mutations that result in Alzheimer's
      disease also decrease the release of CTFgamma. Mutagenesis of the epsilon
      cleavage site in APP mimicked the effects of the FAD mutations, both decreasing
      CTFgamma release and increasing Abeta42 production, suggesting that perturbation
      of this site may account for the observed decrement in gamma-secretase-mediated
      proteolysis of APP. As CTFgamma has been implicated in transcriptional
      activation, these data indicate that decreased signaling and transcriptional
      regulation resulting from FAD mutations in beta-amyloid precursor protein and
      presenilin-1 may contribute to the pathology of Alzheimer's disease.

PMID- 15992374
TI  - Theory for the impact of basal turnover on dopamine clearance kinetics in the rat
      striatum after medial forebrain bundle stimulation and pressure ejection.
AB  - Although microdialysis measurements suggest that extracellular dopamine
      concentrations in the rat striatum are in the low nanomolar range, some recent
      voltammetry studies suggest that the concentration may be considerably higher,
      perhaps in the micromolar range. The presence of such high dopamine levels in the
      extracellular space has to be rationalized with the rapid, linear clearance of
      extracellular dopamine observed after electrical stimulation of the medial
      forebrain bundle. Kinetic analysis of dopamine clearance after evoked release
      suggests that the basal extracellular dopamine concentration is below the K(M) of
      dopamine uptake, which is near 0.2 microm. However, dopamine clearance after
      pressure ejection of dopamine into the rat striatum is slow and non-linear, which
      may alternatively be a sign that basal dopamine release is only slightly slower
      than the maximal velocity of dopamine uptake, Vmax. A high basal extracellular
      dopamine concentration would exist if basal dopamine release were only slightly
      slower than the Vmax of uptake. This report introduces a new kinetic analysis of
      dopamine uptake that sheds light on the possible source of the different
      clearance rates observed following evoked dopamine release and dopamine pressure
      ejection. Furthermore, the analysis rationalizes the rapid dopamine clearance
      after evoked release with the possibility that basal extracellular dopamine
      levels are above the K(M) of the transporter.

PMID- 15992375
TI  - Prostaglandin H(2)-derived adducts of proteins correlate with Alzheimer's disease
      severity.
AB  - The formation of cyclooxygenase-derived lipid adducts of protein in brains of
      patients who had Alzheimer's disease has been investigated. The enzymatic product
      of the cyclooxygenases, prostaglandin H2, rearranges in part to highly reactive
      gamma-ketoaldehydes, levuglandin (LG) E(2) and LGD(2). These gamma-ketoaldehydes
      react with free amines on proteins to yield a covalent adduct. Utilizing analysis
      of the levuglandinyl-lysine adducts by liquid chromatography-tandem mass
      spectrometry, we now find that this post-translational modification is increased
      significantly in the hippocampus in Alzheimer's disease. The magnitude of the
      increase correlates with the pathological evidence of severity.

PMID- 15992376
TI  - Probing the infiltrating character of brain tumors: inhibition of RhoA/ROK
      mediated CD44 cell surface shedding from glioma cells by the green tea catechin
      EGCg.
AB  - Glioma cell-surface binding to hyaluronan (HA), a major constituent of the brain
      extracellular matrix (ECM) environment, is regulated through a complex membrane
      type-1 matrix metalloproteinase (MT1-MMP)/CD44/caveolin interaction that takes
      place at the leading edges of invading cells. In the present study, intracellular
      transduction pathways required for the HA-mediated recognition by infiltrating
      glioma cells in brain was investigated. We show that the overexpression of the
      GTPase RhoA up-regulated MT1-MMP expression and triggered CD44 shedding from the
      U-87 glioma cell surface. This potential implication in cerebral metastatic
      processes was also observed in cells overexpressing the full-length recombinant
      MT1-MMP, while the overexpression of a cytoplasmic domain truncated from of MT1
      MMP failed to do so. This suggests that the cytoplasmic domain of MT1-MMP
      transduces intracellular signaling leading to RhoA-mediated CD44 shedding.
      Treatment of glioma cells with the Rho-kinase (ROK) inhibitor Y27632, or with
      EGCg, a green tea catechin with anti-MMP and anti-angiogenesis activities,
      antagonized both RhoA- and MT1-MMP-induced CD44 shedding. Conversely,
      overexpression of recombinant ROK stimulated CD44 release. Taken together, our
      results suggest that RhoA/ROK intracellular signaling regulates MT1-MMP-mediated
      CD44 recognition of HA. These molecular processes may partly explain the diffuse
      brain-infiltrating character of glioma cells within the surrounding parenchyma
      and thus be a target for new approaches to anti-tumor therapy.

PMID- 15992377
TI  - Treatment of YAC128 mice and their wild-type littermates with cystamine does not
      lead to its accumulation in plasma or brain: implications for the treatment of
      Huntington disease.
AB  - Cystamine is beneficial to Huntington disease (HD) transgenic mice. To elucidate
      the mechanism, cystamine metabolites were determined in brain and plasma of
      cystamine-treated mice. A major route for cystamine metabolism is thought to be:
      cystamine --> cysteamine --> hypotaurine --> taurine. Here we describe an HPLC
      system with coulometric detection that can rapidly measure underivatized
      cystamine, cysteamine and hypotaurine, as well as cysteine and glutathione in the
      same deproteinized tissue sample. A method is also described for the coulometric
      estimation of taurine as its isoindole-sulfonate derivative. Using this new
      methodology we showed that cystamine and cysteamine are undetectable (< or = 0.2
      nmol/100 mg protein) in the brains of 3-month-old HD transgenic (YAC128) mice (or
      their wild-type littermates) treated daily for 2 weeks with cystamine (225 mg/kg)
      in their drinking water. No significant changes were observed in brain
      glutathione and taurine but significant increases were observed in brain
      cysteine. Cystamine and cysteamine were not detected in the plasma of YAC128 mice
      treated daily with cystamine between the ages of 4 and 12 or 7 and 12 months.
      These findings suggest that cystamine is not directly involved in mitigating HD
      but that increased brain cysteine or uncharacterized sulfur metabolites may be
      responsible.

PMID- 15992379
TI  - Proteolytic degradation of glutamate decarboxylase mediates disinhibition of
      hippocampal CA3 pyramidal cells in cathepsin D-deficient mice.
AB  - Although of clinical importance, little is known about the mechanism of seizure
      in neuronal ceroid lipofuscinosis (NCL). In the present study, we have attempted
      to elucidate the mechanism underlying the seizure of cathepsin D-deficient (CD-/
      ) mice that show a novel type of lysosomal storage disease with a phenotype
      resembling late infantile NCL. In hippocampal slices prepared from CD-/- mice at
      post-natal day (P)24, spontaneous burst discharges were recorded from CA3
      pyramidal cells. At P24, the mean amplitude of IPSPs after stimulation of the
      mossy fibres was significantly smaller than that of wild-type mice, which was
      substantiated by the decreased level of gamma-aminobutyric acid (GABA) contents
      in the hippocampus measured by high-performance liquid chromatography (HPLC). At
      this stage, activated microglia were found to accumulate in the pyramidal cell
      layer of the hippocampal CA3 subfield of CD-/- mice. However, there was no
      significant change in the numerical density of GABAergic interneurons in the CA3
      subfield of CD-/- mice at P24, estimated by counting the number of glutamate
      decarboxylase (GAD) 67-immunoreactive somata. In the hippocampus and the cortex
      of CD-/- mice at P24, some GABAergic interneurons displayed extremely high
      somatic granular immunoreactivites for GAD67, suggesting the lysosomal
      accumulation of GAD67. GAD67 levels in axon terminals abutting on to perisomatic
      regions of hippocampal CA3 pyramidal cells was not significantly changed in CD-/-
      mice even at P24, whereas the total protein levels of GAD67 in both the
      hippocampus and the cortex of CD-/- mice after P24 were significantly decreased
      as a result of degradation. Furthermore, the recombinant human GAD65/67 was
      rapidly digested by the lysosomal fraction prepared from the whole brain of wild
      type and CD-/- mice. These observations strongly suggest that the reduction of
      GABA contents, presumably because of lysosomal degradation of GAD67 and lysosomal
      accumulation of its degraded forms, are responsible for the dysfunction of
      GABAergic interneurons in the hippocampal CA3 subfield of CD-/- mice.

PMID- 15992380
TI  - Regional distribution and age-dependent expression of N
      acylphosphatidylethanolamine-hydrolyzing phospholipase D in rat brain.
AB  - The endocannabinoid anandamide (N-arachidonoylethanolamine) and other bioactive
      long-chain N-acylethanolamines are thought to be formed from their corresponding
      N-acylphosphatidylethanolamines by a specific phospholipase D (NAPE-PLD) in the
      brain as well as other tissues. However, regional distribution of NAPE-PLD in the
      brain has not been examined. In the present study, we investigated the expression
      levels of NAPE-PLD in nine different regions of rat brain by enzyme assay,
      western blotting and real-time PCR. The NAPE-PLD activity was detected in all the
      tested brain regions with the highest activity in thalamus. Similar distribution
      patterns of NAPE-PLD were observed at protein and mRNA levels. We also found a
      remarkable increase in the expression levels of protein and mRNA of the brain
      NAPE-PLD with development, which was in good agreement with the increase in the
      activity. The age-dependent increase was also seen with several brain regions and
      other NAPE-PLD-enriched organs (heart and testis). p-Chloromercuribenzoic acid
      and cetyltrimethylammonium chloride, which inhibited recombinant NAPE-PLD dose
      dependently, strongly inhibited the enzyme of all the brain regions. These
      results demonstrated wide distribution of NAPE-PLD in various brain regions and
      its age-dependent expression, suggesting the central role of this enzyme in the
      formation of anandamide and other N-acylethanolamines in the brain.

PMID- 15992381
TI  - Impairment of hippocampal long-term depression and defective spatial learning and
      memory in p35 mice.
AB  - Cdk5 (cyclin-dependent kinase 5) activity is dependent upon association with one
      of two neuron-specific activators, p35 or p39. Genetic deletion of Cdk5 causes
      perinatal lethality with severe defects in corticogenesis and neuronal
      positioning. p35(-/-) mice are viable with milder histological abnormalities.
      Although substantial evidence implicates Cdk5 in synaptic plasticity, its role in
      learning and memory has not been evaluated using mutant mouse models. We report
      here that p35(-/-) mice have deficiencies in spatial learning and memory. Close
      examination of hippocampal circuitry revealed subtle histological defects in CA1
      pyramidal cells. Furthermore, p35(-/-) mice exhibit impaired long-term depression
      and depotentiation of long-term potentiation in the Schaeffer collateral CA1
      pathway. Moreover, the Cdk5-dependent phosphorylation state of protein
      phosphatase inhibitor-1 was increased in 4-week-old mice due to increased levels
      of p39, which co-localized with inhibitor-1 and Cdk5 in the cytoplasm. These
      results demonstrate that p35-dependent Cdk5 activity is important to learning and
      synaptic plasticity. Deletion of p35 may shift the substrate specificity of Cdk5
      due to compensatory expression of p39.

PMID- 15992382
TI  - Proteasome inhibition by lactacystin in primary neuronal cells induces both
      potentially neuroprotective and pro-apoptotic transcriptional responses: a
      microarray analysis.
AB  - Although inhibition of the ubiquitin proteasome system has been postulated to
      play a key role in the pathogenesis of neurodegenerative diseases, studies have
      also shown that proteasome inhibition can induce increased expression of
      neuroprotective heat-shock proteins (HSPs). The global gene expression of primary
      neurons in response to treatment with the proteasome inhibitor lactacystin was
      studied to identify the widest range of possible pathways affected. Our results
      showed changes in mRNA abundance, both at different time points after lactacystin
      treatment and at different lactacystin concentrations. Genes that were
      differentially up-regulated at the early time point but not when most cells were
      undergoing apoptosis might be involved in an attempt to reverse proteasome
      inhibitor-mediated apoptosis and include HSP70, HSP22 and cell cycle inhibitors.
      The up-regulation of HSP70 and HSP22 appeared specific towards proteasome
      inhibitor-mediated cell death. Overexpression of HSP22 was found to protect
      against proteasome inhibitor-mediated loss of viability by up to 25%. Genes
      involved in oxidative stress and the inflammatory response were also up
      regulated. These data suggest an initial neuroprotective pathway involving HSPs,
      antioxidants and cell cycle inhibitors, followed by a pro-apoptotic response
      possibly mediated by inflammation, oxidative stress and aberrant activation of
      cell cycle proteins.

PMID- 15992383
TI  - HPLC conditions are critical for the detection of GABA by microdialysis.
AB  - In microdialysis studies, neither exocytotic release of gamma-aminobutyric acid
      (GABA), nor the presence of GABA type B (GABA(B)) autoreceptors, have been
      clearly established. It was investigated whether the chromatographic separation
      of GABA may have contributed to discrepancies in the literature. After extending
      the profile of the HPLC chromatogram to a retention time of 60 min, it was
      observed that various unknown compounds of biological origin co-eluted near the
      GABA peak. The retention time of GABA appeared to be extremely sensitive to pH;
      even at a retention time of around 60 min there was only a small pH window (5.26
      +/- 0.01) where GABA was consistently well separated from co-eluting compounds.
      GABA determined by the improved assay was sensitive to tetrodotoxin (TTX),
      calcium depletion and the GABA(B) autoreceptor agonist baclofen. The present
      results illustrate that if the proper analytical conditions are applied,
      extracellular GABA can be sampled and quantified by microdialysis in free-moving
      animals. However, when the time-curves are considered, there is a striking delay
      of about 15-30 min before the effects of TTX, calcium depletion or baclofen are
      observed, as compared to the reported response of neurotransmitters such as
      dopamine (less than 5 min). It is assumed that the glial cells serve as a buffer
      between the GABA synapse and the microdialysis probes. It is proposed that
      microdialysis samples measure synaptic GABA indirectly, through glial cells
      surrounding the synapses.

PMID- 15992385
TI  - Evidence for increased expression of the vesicular glutamate transporter, VGLUT1,
      by a course of antidepressant treatment.
AB  - The therapeutic effect of a course of antidepressant treatment is believed to
      involve a cascade of neuroadaptive changes in gene expression leading to
      increased neural plasticity. Because glutamate is linked to mechanisms of neural
      plasticity, this transmitter may play a role in these changes. This study
      investigated the effect of antidepressant treatment on expression of the
      vesicular glutamate transporters, VGLUT1-3 in brain regions of the rat. Repeated
      treatment with fluoxetine, paroxetine or desipramine increased VGLUT1 mRNA
      abundance in frontal, orbital, cingulate and parietal cortices, and regions of
      the hippocampus. Immunoautoradiography analysis showed that repeated
      antidepressant drug treatment increased VGLUT1 protein expression. Repeated
      electroconvulsive shock (ECS) also increased VGLUT1 mRNA abundance in regions of
      the cortex and hippocampus compared to sham controls. The antidepressant drugs
      and ECS did not alter VGLUT1 mRNA abundance after acute administration, and no
      change was detected after repeated treatment with the antipsychotic agents,
      haloperidol and chlorpromazine. In contrast to VGLUT1, the different
      antidepressant treatments did not commonly increase the expression of VGLUT2 or
      VGLUT3 mRNA. These data suggest that a course of antidepressant drug or ECS
      treatment increases expression of VGLUT1, a key gene involved in the regulation
      of glutamate secretion.

PMID- 15992384
TI  - A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6
      hydroxydopamine identifies dopamine transporter mutants impacting transporter
      biosynthesis and trafficking.
AB  - The presynaptic dopamine (DA) transporter (DAT) is a major determinant of
      synaptic DA inactivation, an important target for psychostimulants including
      cocaine and amphetamine, and a mediator of DA neuron vulnerability to the
      neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium ion. To
      exploit genetic approaches for the study of DATs and neural degeneration, we
      exploited the visibility of green fluorescent protein (GFP)-tagged DA neurons in
      transgenic nematodes to implement a forward genetic screen for suppressors of 6
      OHDA sensitivity. In our initial effort, we identified three novel dat-1 alleles
      conferring 6-OHDA resistance. Two of the dat-1 alleles derive from point
      mutations in conserved glycine residues (G55, G90) in contiguous DAT-1
      transmembrane domains (TM1 and TM2, respectively), whereas the third allele
      results in altered translation of the transporter's COOH terminus. Our studies
      reveal biosynthetic, trafficking and functional defects in the DAT-1 mutants,
      exhibited both in vitro and in vivo. These studies validate a forward genetic
      approach to the isolation of DA neuron-specific toxin suppressors and point to
      critical contributions of the mutated residues, as well as elements of the DAT-1
      COOH terminus, to functional expression of catecholamine transporters in neurons.

PMID- 15992386
TI  - Negative regulation of neurotransmitter release by calpain: a possible
      involvement of specific SNAP-25 cleavage.
AB  - Synaptic transmission is conducted by neurotransmitters released from presynaptic
      nerve terminals by means of Ca2+-dependent exocytosis of synaptic vesicles.
      Formation of a complex of soluble N-ethylmaleimide-sensitive fusion protein
      receptor (SNARE) proteins, including vesicle-associated membrane protein-2 (VAMP
      2) in the synaptic vesicle membrane, and syntaxin 1 and synaptosomal-associated
      protein of 25 kDa (SNAP-25) in the plasma membrane, is essential for exocytosis.
      Ionomycin treatment of cultured rat cerebellar granule cells led to cleavage of
      SNAP-25, but not syntaxin 1 and VAMP-2, that was dependent on extracellular Ca2+.
      Cleavage was also induced by N-methyl-D-aspartate (NMDA) treatment, but not by
      depolarization. The use of various site-specific antibodies to SNAP-25, suggested
      that the cleavage site was in the N-terminal domain of SNAP-25. Calpain
      inhibitors abolished the Ca2+-dependent cleavage of SNAP-25 and markedly
      facilitated Ca2+-dependent glutamate (Glu) release from cerebellar granule cells.
      These results suggest that calpain may play an important role in the long-lasting
      regulation of synaptic transmission by suppressing neurotransmitter release,
      possibly through the proteolytic cleavage of SNAP-25.

PMID- 15992388
TI  - One-year outcome with antidepressant treatment of bipolar depression--is the
      glass half empty or half full?

PMID- 15992387
TI  - Treatment with extracellular HSP70/HSC70 protein can reduce polyglutamine
      toxicity and aggregation.
AB  - The accumulation of insoluble protein aggregates is a feature of
      neurodegenerative disease. Overexpression of Heat Shock Protein 70 (HSP70) can
      protect cells with protein aggregates from apoptosis. Another trait of HSP70 is
      its ability to cross the plasma membrane. Therefore, we purified a preparation of
      HSP70/HSC70 from bovine muscle and used it in a model of Huntington's disease.
      Human neuroblastoma SK-N-SH cells were transfected with huntington exon 1 with
      short (25) or long (103) CAG trinucleotide repeats coupled to green flourescent
      protein (GFP). Cells transfected with the long polyCAG repeat had insoluble
      protein aggregates and died through apoptosis. Biotinylated HSP70/HSC70
      incorporated into the culture medium appeared inside the cells within 3-6 h of
      incubation. This incorporation correlated with a reduction in apoptotic cells by
      40-50%. Confocal microscopy revealed that labelled internalized HSP70/HSC70 co
      localized with the polyglutamine inclusions. The measurement of the number and
      size of inclusions showed that HSP70/HSC70 was able to reduce both these
      parameters. A filter trap assay and immunoblotting demonstrated that the
      introduction of HSP70/HSC70 also decreased protein aggregation. Together with
      earlier data on the effects of exogenously administered HSP70/HSC70 on cultured
      cells and on animals, these data show that preparations based on HSP70 may have
      some potential as therapies for a variety of neurodegenerative pathologies.

PMID- 15992389
TI  - Bipolar disorder in women: reproductive events and treatment considerations.
AB  - OBJECTIVE: Bipolar disorders are prevalent in women. Women with bipolar disorder
      often present with different clinical features than men. Reproductive events and
      hormonal treatments may impact the course of bipolar disorder. Our main
      objectives are to i) assess the impact of reproductive events on the course of
      the disorder, and ii) to discuss the relationships between reproductive events
      and psychiatric treatments. METHOD: A literature search was conducted of MEDLINE
      journals from 1965 to present. Manual literature searches were also conducted. We
      review the presentation, clinical course, and treatment considerations of bipolar
      disorder in women, with emphasis on treatment considerations in the context of
      reproductive events. Treatment-related issues such as teratogenicity,
      breastfeeding, polycystic ovarian syndrome, weight gain and obesity, and
      medication interactions with oral contraceptives are reviewed. RESULTS: Women
      with bipolar disorder may be more vulnerable to mood episodes in the context of
      reproductive events, particularly postpartum. In women of reproductive age, mood
      stabilizers must be selected with teratogenic risks in mind, with the highest
      reported risks in pregnancy with valproate, and the greatest concern during
      breastfeeding with lithium use. In the areas of the perimenopause and polycycstic
      ovarian syndrome, more data are needed to advise treatment decisions. CONCLUSION:
      We urgently need further study in these areas to deliver care that is appropriate
      to women with bipolar disorder.

PMID- 15992390
TI  - Clinical issues in perinatal mental health: new developments in the detection and
      treatment of perinatal mood and anxiety disorders.
AB  - OBJECTIVE: This paper presents evidence of new developments in the detection and
      treatment of perinatal mood and anxiety disorders that have relevance for
      clinicians. METHOD: An electronic search was conducted in MEDLINE, CINAHL,
      PsychINFO and The Cochrane Library Database for the interval 1995-2005 for papers
      published in English. RESULTS: New developments were identified as follows: i)
      Broadening frames of reference within perinatal mental health. ii) Impact of
      disorders upon offspring. iii) Identifying women at risk of mental health
      problems. iv) Prevention and early intervention strategies. v) Treatments.
      CONCLUSION: Perinatal mental health is a rapidly expanding field that impacts
      upon the health and wellbeing of all members of families with infants and young
      children. An evidence base for best practice is slowly emerging but considerable
      work is still needed in relation to the identification of women at risk,
      standardisation of diagnostic procedures, reduction of adverse outcomes for women
      and infants, prevention, early intervention, and treatment of clinical disorders.

PMID- 15992391
TI  - One-year outcome with antidepressant--treatment of bipolar depression.
AB  - OBJECTIVE: To examine the risk of relapse into mania or depression with varying
      duration of antidepressant treatment in a cohort of 59 patients with bipolar
      disorder. METHOD: An open naturalistic evaluation using life charting methods of
      patients with 1 year follow-up, who responded to antidepressant treatment and who
      then less or more than 6 months of antidepressant treatment. RESULTS: Patients
      who received more than 6 months of antidepressant treatment were less likely to
      relapse into depression at follow-up of 1 year. There was no difference in
      relapse rates for mania in the different antidepressant treatment duration
      groups. Gender and bipolar subtype did not significantly affect relapse rates for
      depression or mania. CONCLUSION: Our data, taken with other studies, suggest that
      the duration of optimal antidepressant treatment in bipolar disorder must be
      further evaluated.

PMID- 15992392
TI  - Evidence for theory of mind deficits in euthymic patients with bipolar disorder.
AB  - OBJECTIVE: i) To investigate the subtle ToM (theory of mind) deficits in euthymic
      patients with bipolar disorder. ii) To investigate the impact of non-ToM
      cognitive deficits on ToM abilities. METHOD: Forty-three euthymic patients with
      bipolar disorder and 30 healthy control subjects were involved in this study. ToM
      was assessed by the Eyes test and the Hinting task. Both groups were also
      evaluated with a comprehensive neuropsychological battery including tasks for
      basic emotion and face recognition. RESULTS: The patient group was impaired on
      both of the ToM tasks. The patient group also showed impairment in many cognitive
      tasks including tasks related to sustained attention. CONCLUSION: Even euthymic
      patients with bipolar disorder may be impaired in advanced ToM tasks. Executive
      dysfunction and some other cognitives deficits such as basic emotion recognition
      may be at least partly responsible for this result.

PMID- 15992393
TI  - Adjunctive bright light in non-seasonal major depression: results from clinician
      rated depression scales.
AB  - OBJECTIVE: To investigate the use of bright light therapy as an adjunct treatment
      to sertraline in non-seasonal major depression. METHOD: In a randomised double
      blind trial, 102 patients were treated for 5 weeks with either white bright light
      (10 000 lux, 1 h daily) or red dim light (50 lux, 30 min daily). All patients
      were treated with sertraline in a fixed dose of 50 mg daily. The clinician-rated
      depression scales used were the Hamilton Depression Rating Scale (HAM-D17),
      Hamilton six-item subscale (HAM-D6), Melancholia Scale (MES) and the seven
      'atypical' items from the SIGH-SAD. RESULTS: One-hundred and two patients were
      included in the study. Analyses showed that the reduction in depression scores in
      the bright light group was statistically significantly larger than in the dim
      light group on all scales. The scale most sensitive at endpoint was the HAM-D(6),
      which includes the core symptoms of depression. CONCLUSION: The study results
      support the use of bright light as an adjunct treatment to antidepressants in non
      seasonal depression.

PMID- 15992394
TI  - The Temperament and Character Inventory-Revised (TCI-R): psychometric
      characteristics of the French version.
AB  - OBJECTIVE: To explore the psychometric characteristics of a modified version of
      the Cloninger's personality questionnaire, the Temperament and Character
      Inventory-Revised (TCI-R). METHOD: A 482-subject sample, including clinical and
      non-clinical subjects, completed the TCI-R. We performed principal component
      analyses and explored the factorial structure of the questionnaire, and the
      internal consistency of each dimension. RESULTS: The factorial structure of the
      TCI-R was well defined as expected and similar to those shown with the TCI.
      Robust factors were obtained for Reward Dependence and Persistence in the TCI-R,
      even more clearly than in the original TCI. All dimensions obtained higher alpha
      Cronbach coefficients with the TCI-R than with the TCI. We obtained highly
      satisfying reliability coefficients in test-retest and TCI/TCI-R comparisons.
      CONCLUSION: The TCI-R seems to have similar psychometric and feasibility
      characteristics as those of the initial version, but with significant
      improvements in terms of factorial structure and internal consistency of most
      dimensions.

PMID- 15992395
TI  - Prognostic impact of psychoactive substances use during hospitalization for
      intentional drug overdose.
AB  - OBJECTIVE: To assess whether current use of psychoactive substance(s) is a
      prognostic factor during hospitalization for intentional drug overdose (IDO).
      METHOD: Current intoxication with psychoactive substance(s) [cannabis, opiate,
      buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)]
      was identified using toxicological urinalysis in 671 patients with IDO. An IDO
      was a priori defined as serious if associated with one of the following events:
      death, hospitalization in intensive care unit longer than 48 h, respiratory
      support, use of vasopressive drugs, cardiac massage or dialysis. RESULTS:
      Subjects positive for toxicological assays were twice as likely to present with
      serious IDO (OR = 1.9, 95% CI: 1.3-2.8, P = 0.001), independently from a large
      range of confounding factors. The risk of serious IDO was especially marked in
      subjects using LSD, buprenorphine or opiates. CONCLUSION: Systematic
      investigation of substance use could be important to adapt medical management of
      subjects with IDO in general hospital, but also in primary care and psychiatric
      settings.

PMID- 15992396
TI  - The impact of substance use disorders on clinical outcome in 643 patients with
      first-episode psychosis.
AB  - OBJECTIVE: Studies investigating the impact of comorbid substance use disorders
      (SUD) in psychosis have tended to focus on cross-sectional data, with few studies
      examining the effects of substance use course on clinical outcome. The main aim
      of the present study was to assess the impact of baseline SUD and course of SUD
      on remission of positive symptoms. METHOD: The Early Psychosis Prevention and
      Intervention Centre admitted 786 first-episode psychosis (FEP) patients between
      1998 and 2000. Data on SUD and clinical outcome were collected from patients'
      medical records (MR) of 643 patients who met inclusion criteria. RESULTS:
      Lifetime prevalence of SUD was 74%, with 62% having a SUD at baseline. This
      reduced to 36% in those patients who completed 18 months of treatment at the
      EPPIC program. A Cox regression analysis indicated that a decrease or cessation
      of substance use significantly increased the probability of remission, whilst
      persistent SUD substantially reduced the likelihood. In addition, patients who
      reduced use appeared to have better outcomes at 18 months than those patients who
      had never used substances. Baseline SUD was not found to have any significant
      influence on symptom remission. CONCLUSION: Patients presenting with FEP have
      high rates of SUD. Effective management of psychosis within a specialized service
      is associated with reductions in SUD over the course of treatment, although
      persistent substance use is associated with non-compliance, treatment drop-out
      and poor remission rates. As such, young people with FEP and comorbid substance
      use should be offered integrated treatment that addresses both disorders.

PMID- 15992398
TI  - A case of hydrocephalus occlusus presenting as bipolar disorder.
AB  - OBJECTIVE: This case highlights the fact that manic and depressive symptoms can
      be related to hydrocephalus occlusus even in the absence of neurological
      symptoms. METHOD: Single case report. RESULTS: A 22-year-old male patient
      presented with a 2-year history of manic and depressive symptoms. He was admitted
      to psychiatric in-patient care fulfilling sufficient criteria of bipolar disorder
      presenting with a hypomanic state. No neurological symptoms could be detected.
      Three months later, a MRI of the brain showed a hydrocephalus occlusus because of
      a space-occupying lesion of 5 mm in the lamina tecti obstructing the aqueduct of
      Silvius. The MRI also showed parahippocampal changes, which were probably related
      to the hydrocephalus. After the implantation of a ventriculo-peritoneal shunt,
      manic symptoms resolved, but the patient continued to suffer from adynamic
      symptoms. Follow-up MRIs over 3 years showed no progression of the lesion of
      unknown etiology. CONCLUSIONS: In this case, early routine neuroimaging might
      have reduced long-term brain damage. The case underlines that even in the absence
      of neurological symptoms, brain imaging in bipolar disorder might be crucial. The
      feasibility of routine brain imaging in bipolar patients is discussed.

PMID- 15992397
TI  - Personality measures in former heroin users receiving methadone or in protracted
      abstinence from opiates.
AB  - OBJECTIVE: Methadone Maintenance Therapy (MMT) and detoxification to abstinence
      are among the most common treatment options for opiate-dependent patients. This
      paper compares personality traits in detoxified former heroin users and those on
      MMT in order to assess their relevance to treatment selection. METHOD: Twenty-six
      formerly heroin-dependent subjects receiving MMT (MM), 33 formerly heroin
      dependent subjects withdrawn from MMT (MW), and 43 healthy controls were compared
      on the Millon Clinical Multiaxial Inventory-II (MCMI-II) and the Temperament and
      Character Inventory (TCI). RESULTS: On the TCI, MM patients had higher novelty
      seeking and lower self-directedness scores than controls. Both MM and MW subjects
      scored higher than controls on multiple MCMI-II scales. MW but not MM subjects
      scored higher than controls on two Cluster A Scales and the delusional disorder
      scale. CONCLUSION: Schizophrenia-spectrum pathology in former opiate users may be
      greater than previously recognized and could potentially be relevant to treatment
      selection.

PMID- 15992401
TI  - Death, dying and informatics: misrepresenting religion on MedLine.
AB  - BACKGROUND: The globalization of medical science carries for doctors worldwide a
      correlative duty to deepen their understanding of patients' cultural contexts and
      religious backgrounds, in order to satisfy each as a unique individual. To become
      better informed, practitioners may turn to MedLine, but it is unclear whether the
      information found there is an accurate representation of culture and religion. To
      test MedLine's representation of this field, we chose the topic of death and
      dying in the three major monotheistic religions. METHODS: We searched MedLine
      using PubMed in order to retrieve and thematically analyze full-length scholarly
      journal papers or case reports dealing with religious traditions and end-of-life
      care. Our search consisted of a string of words that included the most common
      denominations of the three religions, the standard heading terms used by the
      National Reference Center for Bioethics Literature (NRCBL), and the Medical
      Subject Headings (MeSH) used by the National Library of Medicine. Eligible
      articles were limited to English-language papers with an abstract. RESULTS: We
      found that while a bibliographic search in MedLine on this topic produced instant
      results and some valuable literature, the aggregate reflected a selection bias.
      American writers were over-represented given the global prevalence of these
      religious traditions. Denominationally affiliated authors predominated in
      representing the Christian traditions. The Islamic tradition was under
      represented. CONCLUSION: MedLine's capability to identify the most current,
      reliable and accurate information about purely scientific topics should not be
      assumed to be the same case when considering the interface of religion, culture
      and end-of-life care.

PMID- 15992402
TI  - Lumbar position sense acuity during an electrical shock stressor.
AB  - BACKGROUND: Optimal motor control of the spine depends on proprioceptive input as
      a prerequisite for co-ordination and the stability of the spine. Muscle spindles
      are known to play an important role in proprioception. Animal experiments suggest
      that an increase in sympathetic outflow can depress muscle spindle sensitivity.
      As the muscle spindle may be influenced by sympathetic modulation, we
      hypothesized that a state of high sympathetic activity as during mental stress
      would affect the proprioceptive output from the muscle spindles in the back
      muscles leading to alterations in proprioception and position sense acuity. The
      aim was to investigate the effect of mental stress, in this study the response to
      an electrical shock stressor, on position sense acuity in the rotational axis of
      the lumbar spine. METHODS: Passive and active position sense acuity in the
      rotational plane of the lumbar spine was investigated in the presence and absence
      of an electrical shock stressor in 14 healthy participants. An electrical shock
      threat stressor lasting for approximately 12 minutes was used as imposed stressor
      to build up a strong anticipatory arousal: The participants were told that they
      were going to receive 8 painful electrical shocks however the participants never
      received the shocks. To quantify the level of physiological arousal and the level
      of sympathetic outflow continuous beat-to-beat changes in heart rate (beats x
      min(-1)) and systolic, diastolic and mean arterial blood pressure (mmHg) were
      measured. To quantify position sense acuity absolute error (AE) expressed in
      degrees was measured. Two-way analysis of variance with repeated measurements
      (subjects as random factor and treatments as fixed factors) was used to compare
      the different treatments. RESULTS: Significant increases were observed in
      systolic blood pressure, diastolic blood pressure, and heart rate during the
      stress sessions indicating elevated sympathetic activity (15, 14 and 10%,
      respectively). Despite pronounced changes in the sympathetic activity and
      subjective experiences of stress no changes were found in position sense acuity
      in the rotational plane of the lumbar spine in the presence of the electrical
      shock stressor compared to the control period. CONCLUSION: The present findings
      indicate that position sense acuity in the rotational plane of the spine was
      unaffected by the electrical shock stressor.

PMID- 15992403
TI  - Association of CETP TaqI and APOE polymorphisms with type II diabetes mellitus in
      North Indians: a case control study.
AB  - BACKGROUND: Genetic variants of proteins involved in lipid metabolism may play an
      important role in determining the susceptibility for complications associated
      with type II diabetes mellitus (T2DM). Goal of the present study was to determine
      the association of cholesteryl ester transfer protein TaqI B, D442G, and APOE Hha
      I polymorphisms with T2DM and its complications. METHODS: Study subjects were 136
      patients and 264 healthy controls. All polymorphisms were detected using PCR-RFLP
      and statistical analysis done with chi2 test and ANOVA. RESULTS: Although CETP
      TaqI B polymorphism was not associated with the T2DM, yet B1B2 genotype was
      significantly (p = 0.028) associated with high risk of hypertension in diabetic
      patients (OR = 3.068, 95% CI 1.183-7.958). In North Indians D442G variation in
      CETP gene was found to be absent. Frequency of APOE HhaI polymorphism was also
      not different between patients and controls. In diabetic patients having
      neuropathy and retinopathy significantly different levels of total-cholesterol
      [(p = 0.001) and (p = 0.029) respectively] and LDL-cholesterol [(p = 0.001) and
      (p = 0.001) respectively] were observed when compared to patients with T2DM only.
      However, lipid levels did not show any correlation with the CETP TaqI B and APOE
      Hha I genetic polymorphisms. CONCLUSION: CETP TaqI B and APOE HhaI polymorphism
      may not be associated with type II diabetes mellitus in North Indian population,
      however CETP TaqI B polymorphism may be associated with hypertension along with
      T2DM.

PMID- 15992404
TI  - Direct microcontact printing of oligonucleotides for biochip applications.
AB  - BACKGROUND: A critical step in the fabrication of biochips is the controlled
      placement of probes molecules on solid surfaces. This is currently performed by
      sequential deposition of probes on a target surface with split or solid pins. In
      this article, we present a cost-effective procedure namely microcontact printing
      using stamps, for a parallel deposition of probes applicable for manufacturing
      biochips. RESULTS: Contrary to a previous work, we showed that the stamps
      tailored with an elastomeric poly(dimethylsiloxane) material did not require any
      surface modification to be able to adsorb oligonucleotides or PCR products. The
      adsorbed DNA molecules are subsequently printed efficiently on a target surface
      with high sub-micron resolution. Secondly, we showed that successive stamping is
      characterized by an exponential decay of the amount of transferred DNA molecules
      to the surface up the 4th print, then followed by a second regime of transfer
      that was dependent on the contact time and which resulted in reduced quality of
      the features. Thus, while consecutive stamping was possible, this procedure
      turned out to be less reproducible and more time consuming than simply re-inking
      the stamps between each print. Thirdly, we showed that the hybridization signals
      on arrays made by microcontact printing were 5 to 10-times higher than those made
      by conventional spotting methods. Finally, we demonstrated the validity of this
      microcontact printing method in manufacturing oligonucleotides arrays for
      mutations recognition in a yeast gene. CONCLUSION: The microcontact printing can
      be considered as a new potential technology platform to pattern DNA microarrays
      that may have significant advantages over the conventional spotting technologies
      as it is easy to implement, it uses low cost material to make the stamp, and the
      arrays made by this technology are 10-times more sensitive in term of
      hybridization signals than those manufactured by conventional spotting
      technology.

PMID- 15992406
TI  - Quality assessment of microarrays: visualization of spatial artifacts and
      quantitation of regional biases.
AB  - BACKGROUND: Quality-control is an important issue in the analysis of gene
      expression microarrays. One type of problem is regional bias, in which one region
      of a chip shows artifactually high or low intensities (or ratios in a two-channel
      array) relative to the majority of the chip. Current practice in quality
      assessment for microarrays does not address regional biases. RESULTS: We present
      methods implemented in R for visualizing regional biases and other spatial
      artifacts on spotted microarrays and Affymetrix chips. We also propose a
      statistical index to quantify regional bias and investigate its typical
      distribution on spotted and Affymetrix arrays. We demonstrate that notable
      regional biases occur on both Affymetrix and spotted arrays and that they can
      make a significant difference in the case of spotted microarray results. Although
      strong biases are also seen at the level of individual probes on Affymetrix
      chips, the gene expression measures are less affected, especially when the RMA
      method is used to summarize intensities for the probe sets. A web application
      program for visualization and quantitation of regional bias is provided at
      http://www.discover.nci.nih.gov/affytools. CONCLUSION: Researchers should
      visualize and measure the regional biases and should estimate their impact on
      gene expression measurements obtained. Here, we (i) introduce pictorial
      visualizations of the spatial biases; (ii) present for Affymetrix chips a useful
      resolution of the biases into two components, one related to background, the
      other to intensity scale factor; (iii) introduce a single parameter to reflect
      the global bias present across an array. We also examine the pattern distribution
      of such biases and conclude that algorithms based on smoothing are unlikely to
      compensate adequately for them.

PMID- 15992405
TI  - Ukrain - a new cancer cure? A systematic review of randomised clinical trials.
AB  - BACKGROUND: Ukrain is an anticancer drug based on the extract of the plant
      Chelidonium majus L. Numerous pre-clinical and clinical investigations seem to
      suggest that Ukrain is pharmacologically active and clinically effective. We
      wanted therefore to critically evaluate the clinical trial data in the form of a
      systematic review. METHODS: Seven electronic databases were searched for all
      relevant randomised clinical trials. Data were extracted and validated by both
      authors, tabulated and summarised narratively. The methodological quality was
      assessed with the Jadad score. RESULTS: Seven trials met our inclusion criteria.
      Without exception, their findings suggest that Ukrain has curative effects on a
      range of cancers. However, the methodological quality of most studies was poor.
      In addition, the interpretation of several trials was impeded by other problems.
      CONCLUSION: The data from randomised clinical trials suggest Ukrain to have
      potential as an anticancer drug. However, numerous caveats prevent a positive
      conclusion, and independent rigorous studies are urgently needed.

PMID- 15992407
TI  - A new short-term toxicity assay using Aspergillus awamori with recombinant
      aequorin gene.
AB  - BACKGROUND: Most currently available short-term toxicity assays are based on
      bacterial cells. Therefore there is a need for novel eukaryotic microbial
      bioassays that will be relevant to higher eukaryotes such as animals and plants.
      Ca2+ is a universal intracellular signalling molecule found in all organisms from
      prokaryotes to highly specialized animal cells. In fungi calcium has been
      demonstrated to be involved in control of many important processes. The
      recombinant aequorin gene from the jellyfish Aequorea victoria responsible for
      the expression of the Ca2+-sensitive aequorin photoprotein has been cloned in the
      filamentous fungus Aspergillus awamori. This has allowed real life monitoring of
      [Ca2+]c changes in living fungal cells. When subjected to different physico
      chemical stimuli fungal cells respond by transiently changing the concentration
      of free Ca2+ in the cytosol ([Ca2+]c) and the pattern of these changes (Ca2+
      signature) is specific to each particular stimulus. Therefore it was interesting
      to investigate whether different environmental toxicants would be able to affect
      the pattern of [Ca2+]c changes in a reproducible and dose dependant manner.
      RESULTS: Toxicity bioassay has been developed to monitor changes [Ca2+]c of the
      recombinant fungus in the presence of toxicants representing heavy metals--Cr6+
      and Zn2+ and a phenolic polar narcotic -3,5-DCP. The fungus responds to toxicants
      by a decrease in the amplitude of [Ca2+]c response to 5 mM external CaCl2 and an
      increase in Ca2+ final resting levels and recovery time. CONCLUSION: A novel
      toxicity bioassay utilizing eukaryotic cells has been developed based on
      filamentous fungi transformed with the recombinant aequorin gene. A range of
      parameters characterising changes in [Ca2+]c has been identified, e.g. Amplitude,
      Length of Transient, Final Resting Level and Recovery Time. These parameters can
      be used to determine the toxicity of a range of chemicals to eukaryotic cells in
      a 96-well microtitre plate method.

PMID- 15992408
TI  - Normative data of bone Mineral Density in healthy population of Tehran, Iran: a
      cross sectional study.
AB  - BACKGROUND: Osteoporosis is a major problem and is a hidden epidemic disease in
      the world. Early diagnosis by measurement of Bone Mineral Density (BMD) and
      treatment can prevent and reduce disease complications, especially fractures. As
      there is no comprehensive study in Iran, this study designed to assess BMD
      discrepancy in 20-69 yr Tehran population as well as prevalence of osteoporosis
      and osteopenia. METHODS: 553 people (34% men, 66%women) from 50 Blocks in Tehran
      randomly selected. The assessment of BMD in spine and femur region performed
      through DXA method. All subjects clinically examined and their BMIs determined.
      RESULTS: The average spinal BMD score in men were more than in women. The peak
      bone mass of spine bone both in men and women occurred during 20-29 yr and
      reduction began from the age of 40. At the age of 60 to 69, loose of bone density
      was 19.6% in lumbar spine and 18.5% in femur of women and also 7.9% in lumbar
      spine and 14.6% in femur of men. Prevalence of osteoporosis in this age group in
      lumbar spine and femur was 32.4% and 5.9% in women and 9.4% and 3.1% in men
      respectively. CONCLUSION: In all age groups, peak bone mass was lower than
      European or American population, whereas the rate of bone loss was as much as the
      some population and actually this process justifies the prevalence of
      osteoporosis and osteopenia in Tehran population.

PMID- 15992409
TI  - Prediction of twin-arginine signal peptides.
AB  - BACKGROUND: Proteins carrying twin-arginine (Tat) signal peptides are exported
      into the periplasmic compartment or extracellular environment independently of
      the classical Sec-dependent translocation pathway. To complement other methods
      for classical signal peptide prediction we here present a publicly available
      method, TatP, for prediction of bacterial Tat signal peptides. RESULTS: We have
      retrieved sequence data for Tat substrates in order to train a computational
      method for discrimination of Sec and Tat signal peptides. The TatP method is able
      to positively classify 91% of 35 known Tat signal peptides and 84% of the
      annotated cleavage sites of these Tat signal peptides were correctly predicted.
      This method generates far less false positive predictions on various datasets
      than using simple pattern matching. Moreover, on the same datasets TatP generates
      less false positive predictions than a complementary rule based prediction
      method. CONCLUSION: The method developed here is able to discriminate Tat signal
      peptides from cytoplasmic proteins carrying a similar motif, as well as from Sec
      signal peptides, with high accuracy. The method allows filtering of input
      sequences based on Perl syntax regular expressions, whereas hydrophobicity
      discrimination of Tat- and Sec-signal peptides is carried out by an artificial
      neural network. A potential cleavage site of the predicted Tat signal peptide is
      also reported. The TatP prediction server is available as a public web server at
      http://www.cbs.dtu.dk/services/TatP/.

PMID- 15992410
TI  - Inhibition of Tat activity by the HEXIM1 protein.
AB  - BACKGROUND: The positive transcription elongation factor b (P-TEFb) composed by
      CDK9/CyclinT1 subunits is a dedicated co-factor of HIV transcriptional
      transactivator Tat protein. Transcription driven by the long terminal repeat
      (LTR) of HIV involves formation of a quaternary complex between P-TEFb, Tat and
      the TAR element. This recruitment is necessary to enhance the processivity of RNA
      Pol II from the HIV-1 5' LTR promoter. The activity of P-TEFb is regulated in
      vivo and in vitro by the HEXIM1/7SK snRNA ribonucleic-protein complex. RESULTS:
      Here we report that Tat transactivation is effectively inhibited by co-expression
      of HEXIM1 or its paralog HEXIM2. HEXIM1 expression specifically represses
      transcription mediated by the direct activation of P-TEFb through artificial
      recruitment of GAL4-CycT1. Using appropriate HEXIM1 mutants we determined that
      effective Tat-inhibition entails the 7SK snRNA basic recognition motif as well as
      the C-terminus region required for interaction with cyclin T1. Enhanced
      expression of HEXIM1 protein modestly affects P-TEFb activity, suggesting that
      HEXIM1-mediated repression of Tat activity is not due to a global inhibition of
      cellular transcription. CONCLUSION: These results point to a pivotal role of P
      TEFb for Tat's optimal transcription activity and suggest that cellular proteins
      that regulate P-TEFb activity might exert profound effects on Tat function in
      vivo.

PMID- 15992411
TI  - A two-dimensional mathematical model of non-linear dual-sorption of percutaneous
      drug absorption.
AB  - BACKGROUND: Certain drugs, for example scopolamine and timolol, show non-linear
      kinetic behavior during permeation process. This non-linear kinetic behavior is
      due to two mechanisms; the first mechanism being a simple dissolution producing
      mobile and freely diffusible molecules and the second being an adsorption process
      producing non-mobile molecules that do not participate in the diffusion process.
      When such a drug is applied on the skin surface, the concentration of the drug
      accumulated in the skin and the amount of the drug eliminated into the blood
      vessel depend on the value of a parameter, C, the donor concentration. The
      present paper studies the effect of the parameter value, C, when the region of
      the contact of the skin with drug, is a line segment on the skin surface. To
      confirm that dual-sorption process gives an explanation to non-linear kinetic
      behavior, the characteristic features that are used in one-dimensional models are
      (1) prolongation of half-life if the plot of flux versus time are straight lines
      soon after the vehicle removal, (2) the decrease in half-life with increase in
      donor concentration. This paper introduces another feature as a characteristic to
      confirm that dual-sorption model gives an explanation to the non-linear kinetic
      behavior of the drug. This new feature is "the prolongation of half-life is not a
      necessary feature if the plots of drug flux versus time is a non-linear curve,
      soon after the vehicle removal". METHODS: From biological point of view, a drug
      absorption model is said to be nonlinear if the sorption isotherm is non-linear.
      When a model is non-linear the relationship between lag-time and donor
      concentration is non-linear and the lag time decreases with increase in donor
      concentration. A two-dimensional dual-sorption model is developed for
      percutaneous absorption of a drug, which shows non-linear kinetic behavior in the
      permeation process. This model may be used when the diffusion of the drug in the
      direction parallel to the skin surface must be examined, as well as in the
      direction into the skin, examined in one-dimensional models. The dual-sorption
      model is an initial/boundary value problem which consists of (1) one non-linear,
      two-dimensional, second-order parabolic equation, (2) boundary conditions, (3)
      one initial condition. Note that, the number of boundary conditions are, six and
      four, respectively, if the permeation process under consideration is, during the
      application of the vehicle and during the removal of the vehicle. Adopting the
      approach of method of lines, the initial/boundary value problem is transformed
      into an initial-value problem, which consists of (1) a system of non-linear
      ordinary differential equations, (2) one initial condition. The system of non
      linear ordinary differential equations contains time-dependent non-homogeneous
      terms, if the permeation process under consideration is, during the application
      of the vehicle. To solve this initial-value problem, an eight-stage sequential
      algorithm which is second-order accurate, and requires only tri-diagonal solvers,
      is developed. RESULTS: Simulation of the numerical methods described is carried
      out with various values of the parameter C. The illustrations are given in the
      form of figures. The concentration profiles are viewed as parabolas along the
      mesh lines parallel to x-axis or y-axis. The flow rates in different subregions
      of the skin-region are studied. The shapes of the concentration profiles are
      examined before and after the steady-state concentration is reached. The
      concentration reaches steady-state when the flux reaches the steady state. The
      plots of flux versus time and cumulative amount of drug eliminated into the
      receptor cell versus time are given. CONCLUSION: Based on the various values of
      the parameter, C, conclusions are drawn about (1) flow rate of the drug in
      different regions of the skin, (2) shape of the concentration profiles, (3) the
      time required to reach the steady-state value of the concentration, (4)
      concentration of the drug in different regions of the skin, when steady-state
      value of the concentration is reached, (5) the time required to reach the steady
      state value of the flux, (6) time required to reach the steady-state value of the
      concentration of the drug, (7) half-life of the concentration of the drug and (8)
      lag-time. A comparison, between this two-dimensional model and the one
      dimensional non-linear dual-sorption model that exists in the literature, is done
      based on (1) the shape of the concentration profiles at various time levels, (2)
      the time required to reach the steady-state value of the concentration, (3) lag
      time and (4) half-life.

PMID- 15992417
TI  - Neurological complications after surgery. Abstracts of the 2nd International
      Symposium on the Pathophysiology of Cardiopulmonary Bypass. Aachen, Germany, 3
      December 1999.

PMID- 15992412
TI  - Are antifibrinolytic drugs equivalent in reducing blood loss and transfusion in
      cardiac surgery? A meta-analysis of randomized head-to-head trials.
AB  - BACKGROUND: Aprotinin has been shown to be effective in reducing peri-operative
      blood loss and the need for re-operation due to continued bleeding in cardiac
      surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid
      (EACA) are cheaper, but it is not known if they are as effective as aprotinin.
      METHODS: Studies were identified by searching electronic databases and
      bibliographies of published articles. Data from head-to-head trials were pooled
      using a conventional (Cochrane) meta-analytic approach and a Bayesian approach
      which estimated the posterior probability of TXA and EACA being equivalent to
      aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of
      transfusion or re-operation because of bleeding. RESULTS: Peri-operative blood
      loss was significantly greater with TXA and EACA than with aprotinin: weighted
      mean differences were 106 mls (95% CI 37 to 227 mls) and 185 mls (95% CI 134 to
      235 mls) respectively. The pooled relative risks (RR) of receiving an allogeneic
      red blood cell (RBC) transfusion with TXA and EACA, compared with aprotinin, were
      1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI 0.84 to 1.55) respectively. The
      equivalent Bayesian posterior mean relative risks were 1.15 (95% Bayesian
      Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI 0.79 to 1.82)
      respectively. For transfusion, using a 20% non-inferiority boundary, the
      posterior probabilities of TXA and EACA being non-inferior to aprotinin were 0.82
      and 0.76 respectively. For re-operation the Cochrane RR for TXA vs. aprotinin was
      0.98 (95% CI 0.51 to 1.88), compared with a posterior mean Bayesian RR of 0.63
      (95% BCI 0.16 to 1.46). The posterior probability of TXA being non-inferior to
      aprotinin was 0.92, but this was sensitive to the inclusion of one small trial.
      CONCLUSION: The available data are conflicting regarding the equivalence of
      lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion
      and the need for re-operation. Decisions are sensitive to the choice of clinical
      outcome and non-inferiority boundary. The data are an uncertain basis for
      replacing aprotinin with the cheaper lysine analogues in clinical practice.
      Progress has been hampered by small trials and failure to study clinically
      relevant outcomes.

PMID- 15992418
TI  - Abstracts of the 3rd International Symposium on the Pathophysiology of
      Cardiopulmonary Bypass. Myocardial cell damage and myocardial protection. Aachen,
      Germany. 16 December 2000.

PMID- 15992421
TI  - Resorbable extracellular matrix grafts in urologic reconstruction.
AB  - PURPOSE: There is an increasingly large body of literature concerning tissue
      engineering products that may be used in urology. Some of these are quite complex
      (such as multilayer patient-specific cell-seeded implants) yet the most simple
      and successful products to date are also the most uncomplicated: resorbable
      acellular extra-cellular matrices (ECMs) harvested from animals. ECMs have been
      used in a variety of difficult urologic reconstruction problems, and this review
      is intended to summarize this complex literature for the practicing urologist.
      METHODS: Medline search of related terms such as "SIS, small intestinal
      submucosa, ECM, extracellular matrix, acellular matrix and urologic
      reconstruction". Manuscripts missed in the initial search were taken from the
      bibliographies of the primary references. RESULTS: Full review of potential
      clinical uses of resorbable extra-cellular matrices in urologic reconstruction.
      CONCLUSIONS: Currently, the "state of the art" in tissue engineering solutions
      for urologic reconstruction means resorbable acellular xenograft matrices. They
      show promise when used as a pubovaginal sling or extra bolstering layers in
      ureteral or urethral repairs, although recent problems with inflammation
      following 8-ply pubovaginal sling use and failures after 1- and 4-ply SIS repair
      of Peyronie's disease underscore the need for research before wide adoption.
      Preliminary data is mixed concerning the potential for ECM urethral patch graft,
      and more data is needed before extended uses such as bladder augmentation and
      ureteral replacement are contemplated. The distant future of ECMs in urology
      likely will include cell-seeded grafts with the eventual hope of producing "off
      the shelf" replacement materials. Until that day arrives, ECMs only fulfill some
      of the requirements for the reconstructive urologist.

PMID- 15992422
TI  - 17-year follow-up of a randomized prospective controlled trial of adjuvant
      intravesical doxorubicin in the treatment of superficial bladder cancer.
AB  - PURPOSE: To evaluate the efficacy of adjuvant intravesical doxorubicin in
      superficial transitional cell carcinoma of the urinary bladder on long-term
      follow-up. MATERIALS AND METHODS: Between July 1986 and November 1991, all
      patients harboring superficial bladder cancers (Ta or T1) with one or more of
      these criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors) were
      randomized to receive either 50 mg doxorubicin or no adjuvant therapy. Patients
      with recurrences were allowed to receive doxorubicin or other intravesical
      agents. Recurrence, progression and survival were analyzed. RESULTS: There were
      82 patients included (64 males and 18 females). The mean age was 64 years. Forty
      six patients were randomized to the doxorubicin group and 36 to the control
      group. Final analysis was made at median follow-up of 45, 128 and 131.5 months
      for recurrence, progression and survival, respectively. Recurrence free,
      progression free and disease specific survival did not differ significantly
      between groups. The 10-year Kaplan-Meier estimates for recurrence free,
      progression free and disease specific survival were 67%, 84% and 92%,
      respectively for the doxorubicin group, and were 50%, 89% and 97%, respectively
      for the control group. Tumor size predicted recurrence (p=0.013) and grade
      predicted progression (p=0.004) with multivariate analysis. CONCLUSIONS: Adjuvant
      intravesical doxorubicin could not be shown to improve recurrence, progression
      and survival of superficial bladder cancer, compared with control on long-term
      follow-up. Tumor size and grade were shown to be prognostic factors for
      recurrence and progression, respectively.

PMID- 15992423
TI  - Stapleless laparoscopic assisted radical cystectomy with ileal neobladder in a
      male and with ileal loop in a female: initial report from Brazil.
AB  - INTRODUCTION: Here, we report our initial experience with laparoscopic assisted
      radical cystectomy without the use of surgical staples. CASES REPORT: A 70 year
      old male and a 55 year old female were diagnosed to have T2G3 transitional cell
      carcinoma of the bladder with negative metastatic work-out. Both patients were
      scheduled and agreed to a laparoscopic assisted radical cystectomy. In both
      cases, urinary diversion (orthotopic ileal Studer neobladder in the male and
      ileal conduit in the female) was performed extracorporeally following radical
      cystectomy. In both cases control of the bladder vascular pedicle was
      accomplished with a combination of metallic and hem-o-lock clips. The total
      surgical time was 6.5 hours in both cases. Estimated intra-operative blood loss
      was 500 cc and 350 cc respectively, however both patients required postoperative
      blood transfusions. No intraoperative complications occurred. In both cases,
      pathology revealed negative surgical margins. CONCLUSIONS: Extracorporeal
      creation of urinary diversion decrease the overall operative time. Laparoscopic
      pelvic lymphadenectomy can be performed following the extended template. The use
      of surgical clips instead of vascular Endo-GIA titanium staples to control the
      bladder vascular pedicles is feasible and safe in selected patients, thus
      reducing intraoperative surgical costs. Considerable experience with laparoscopic
      radical prostatectomy is necessary before one attempts laparoscopic radical
      cystectomy.

PMID- 15992424
TI  - Survival of patients with prostate cancer and normal PSA levels treated by
      radical prostatectomy.
AB  - INTRODUCTION: The unpredictability of prostate cancer has become a daily
      challenge for the urologist, with different strategies being required to manage
      these cases. In this study, we report on the perspectives for curing prostate
      cancer in males undergoing radical prostatectomy with Gleason score of 2-6 on
      prostate biopsy in relation to pre-operative PSA levels. MATERIALS AND METHODS:
      From 1991-- 2000, we selected 440 individuals whose pathological diagnosis
      revealed a Gleason score of 2-6 upon prostate biopsy and who subsequently
      underwent retro-pubic radical prostatectomy due to localized prostate cancer. The
      clinical stage identified in the group under study was T1c: 206 (46.8%); T2a: 122
      (27.7%); T2b: 93 (21.1%); T2c: 17 (3.9%); T3a: 2 (0.5%). Following surgery, we
      constructed a biochemical recurrence-free survival curve according to pre
      operative PSA levels between 0-4; 4.1-10; 10.1-20 and > 20 ng/mL, with a median
      follow-up of 5 years. RESULTS: Following radical prostatectomy, the pathological
      stage was confirmed as pT2a: 137 (31.1%); T2b: 118 (26.8%); T2c: 85 (19.3%); T3a:
      67 (15.2%); T3b: 6 (1.4%); T3c: 22 (5%). The biochemical recurrence-free
      survival, according to PSA values between 0-4; 4.1-10; 10.1-20 and > 20 ng/mL,
      was 86.6%, 62.7%, 39.8% and 24.8% respectively. CONCLUSION: Better chances for
      curing low-grade prostate cancer occur in individuals with normal PSA for whom a
      biopsy is not usually recommended.

PMID- 15992425
TI  - Preliminary experience with extraperitoneal endoscopic radical prostatectomy
      through duplication of the open technique.
AB  - OBJECTIVE: To describe surgical and functional results with extraperitoneal
      laparoscopic radical prostatectomy with duplication of the open technique, from
      the experience obtained in the treatment of 28 initial cases. MATERIALS AND
      METHODS: In a 36-month period, we prospectively analyzed 28 patients diagnosed
      with localized prostate cancer undergoing extraperitoneal laparoscopic radical
      prostatectomy. RESULTS: Mean surgical time was 280 min, with mean blood loss of
      320 mL. As intraoperative complications, there were 2 rectal lesions repaired
      with laparoscopic suture in 2 planes. There was no conversion to open surgery.
      Median hospital stay was 3 days, with return to oral diet in the first post
      operative day in patients. As post-operative complications, there were 3 cases of
      extraperitoneal urinary fistula. Two of these cases were resolved by maintaining
      a Foley catheter for 21 days, and the other one by late endoscopic reintervention
      for repositioning the catheter. Five out of 18 previously potent patients evolved
      with erectile dysfunction. The diagnosis of prostate cancer was confirmed in all
      patients, with focal positive margin occurring in 3 cases. During a mean follow
      up of 18 months, 2 patients presented increased PSA, with no clinical evidence of
      disease. CONCLUSION: Laparoscopic radical prostatectomy is a laborious and
      difficult procedure, with a long learning curve. Extraperitoneal access is
      feasible, and it is possible to practically duplicate the principles of open
      surgery. The present technique can possibly offer advantages in terms of
      decreased blood loss, preservation of erectile function and prevention of
      positive margins.

PMID- 15992426
TI  - Single nucleotide polymorphisms of the heat shock protein 90 gene in varicocele
      associated infertility.
AB  - PURPOSE: Varicoceles are associated with impaired testicular function and male
      infertility, but the molecular mechanisms by which fertility is affected have not
      been satisfactorily explained. Spermatogenesis might be affected by increased
      scrotal temperature, such as that caused by varicocele. HSP90 is a molecular
      chaperone expressed in germ cells and is related to spermatogenesis, motility,
      and both heat and oxidative stress. Possible correlations between coding single
      region nucleotide polymorphisms (cSNPs) in the HSP90 gene in patients with
      varicocele associated with infertility were analyzed, and polymorphisms in these
      exons were characterized through DNA sequencing. MATERIALS AND METHODS: PCR-SSCP
      and DNA sequencing were used to search for mutations in 18 infertile patients
      with varicocele, 11 patients with idiopathic infertility and 12 fertile men. DNA
      was extracted from leucocytes for PCR amplification and SSCP analysis. DNA from
      samples with an altered band pattern in the SSCP was then sequenced to search for
      polymorphisms. RESULTS: Three silent polymorphisms that do not lead to amino acid
      substitutions were identified. CONCLUSION: Mutations in the HSP90 gene do not
      appear to be a common cause of male factor infertility. The low incidence of gene
      variation, or SNPs, in infertile men demonstrates that this gene is highly
      conserved and thus confirms its key role in spermatogenesis and response to heat
      stress.

PMID- 15992427
TI  - Deep-seated sarcomas of the penis.
AB  - Mesenchymal neoplasias represent 5% of tumors affecting the penis. Due to the
      rarity of such tumors, there is no agreement concerning the best method for
      staging and managing these patients. Sarcomas of the penis can be classified as
      deep-seated if they derive from the structures forming the spongy body and the
      cavernous bodies. Superficial lesions are usually low-grade and show a small
      tendency towards distant metastasis. In contrast, deep-seated lesions usually
      show behavior that is more aggressive and have poorer prognosis. The authors
      report 3 cases of deep-seated primary sarcomas of the penis and review the
      literature on this rare and aggressive neoplasia.

PMID- 15992428
TI  - Kidney carcinoma associated with Xp11.2 translocation / TFE3 (ASPL-TFE3) gene
      fusion.
AB  - We report the case of a 58-year old patient, showing a solid image in the right
      kidney, who underwent radical nephrectomy that revealed neoplasia, whose
      pathological study led to the diagnosis of kidney carcinoma associated with
      Xp11.2 translocation / TFE3 (ASPL-TFE3) gene fusion. The authors discuss aspects
      related to this lesion, such as frequency, pathogenesis, clinical presentation,
      histopathology and outcome, as observed in the literature.

PMID- 15992429
TI  - Pseudo-Meigs' syndrome associated to renal pelvis tumor.
AB  - INTRODUCTION: Pseudo-Meigs' syndrome is associated with tumors different from the
      benign ovary tumor, but it has never been described in association to
      transitional cell carcinoma. CASE REPORT: A female 73 year-old patient presenting
      pleural effusion nonmetastatic associated with renal pelvis transitional cell
      carcinoma that resolved and did not recur after radical nephroureterectomy.
      COMMENTS: Renal pelvis transitional cell carcinoma can result in the Pseudo
      Meigs' syndrome. Although being a rare clinical entity, the identification of
      such syndrome can result in an accurate diagnosis, leading to an efficient
      surgical treatment, without comorbidity for the patient.

PMID- 15992430
TI  - Intermittent bladder urinary retention in a young woman. An unusual presentation
      of partial urethral duplication.
AB  - A singular case of female accessory urethra associated to a mobile bladder stone
      with an unusual clinical presentation is reported. The role of perineal
      ultrasound is emphasized as a useful diagnostic tool to study female urethra in a
      static and dynamic setting, including cases of partial or complete urethral
      duplication.

PMID- 15992431
TI  - Traumatic degloving lesion of penile and scrotal skin.
AB  - Avulsions of penile and scrotal skin are uncommon events and are caused mainly by
      accidents with industrial machines and agricultural machine belts. We report the
      case of a 30-year old patient with avulsion and traumatic degloving of the penile
      and scrotal skin, with exposure of the cavernous bodies, spongy body, and testes
      due to an industrial machine accident. Reconstruction was performed in steps,
      achieving a satisfactory esthetic result, normal voiding and reestablished sexual
      function.

PMID- 15992432
TI  - Management of complete ureteral obstructions with a transluminal puncture
      technique.
AB  - INTRODUCTION: The traditional delayed treatment of iatrogenic complete ureteral
      obstruction is open surgery. An easy endourological technique, transluminal re
      canalization of the ureter by guide-wire puncture under fluoro-endoscopic
      control, which has been performed on 4 patients, is described. SURGICAL
      TECHNIQUE: With the guidance of C-arm fluoroscopy, by moving the C-arm to
      different planes, the tip of the ureteroscope is directed to the correct plane to
      meet the obliterated proximal end of the ureter and under direct vision,
      transluminal puncture is performed using the stiff end of a 0.035-inch guide
      wire. Once the stiff end of the guide-wire is in the lumen of the proximal
      ureter, an ureteral catheter is introduced over the guide wire, the guide wire is
      then removed and reinserted through the ureteral catheter with its soft end
      leading and a double J catheter is inserted. Ureteral stricture, if later
      encountered, is treated with balloon dilatation. RESULTS: Continuity of the
      ureter was restored in all 4 patients. The double J stents were removed 6 weeks
      later and a retrograde pyelography revealed resolution of the hydronephrosis
      without extravasation of urine. CONCLUSION: Although a very satisfactory result
      was achieved in our cases, more cases are needed to show if it can be an
      alternative to conventional surgical repair. However, we believe that this
      minimally invasive technique can be used for short obliterated ureteral segments
      and neither delays nor does it preclude further management using open surgery.

PMID- 15992433
TI  - Re: Radiological classification of renal angiomyolipomas based on 127 tumors.

PMID- 15992454
TI  - Manual acupuncture needle stimulation of the rat hindlimb activates groups I, II,
      III and IV single afferent nerve fibers in the dorsal spinal roots.
AB  - Using single unit nerve recording techniques in rats, the present experiment
      aimed to determine which specific population of afferent nerve fibers (groups I,
      II, III and IV) in the dorsal roots at the 4th or 5th lumbar segments (L4 or L5)
      are activated during manual acupuncture needle stimulation. An acupuncture needle
      300-340 microm in diameter was inserted into the skin and underlying muscles
      around the Zusanli acupoint (ST36) area in the hindlimbs, and was manually
      rotated right and left at a frequency of about 1 Hz for 1 min. The dorsal root of
      the L4 and L5 spinal nerve was cut close to the entrance into the spinal cord
      after laminectomy and dissected free to record unitary afferent nerve activity. A
      single afferent fiber activated by acupuncture stimulation was identified by the
      identical shape of the discharge spikes during stimulation and during
      electrically evoked action potentials induced by single pulse electrical
      stimulation of the sciatic nerve. The conduction velocity of the afferent fiber
      was calculated by the latency of the electrically evoked action potential. A
      total of 35 units were intentionally recorded from all animals in order to
      include all 4 afferent fiber groups. Units were spontaneously silent in the
      absence of stimulation, while all units responded to ipsilateral manual rotation
      of the acupuncture needle. The conduction velocity of all 35 units ranged between
      0.8 and 86.0 m/s, thus belonging to groups I-V fibers. Mean conduction velocity
      of groups I, II, III and IV were 57.9 m/s (n = 13), 42.9 m/s (n = 11), 10.3 m/s
      (n = 6) and 1.2 m/s (n = 5), respectively. Mean discharge rates during
      acupuncture stimulation of groups I, II, III and IV afferents were 7.4 Hz, 6.2
      Hz, 4.7 Hz and 0.4 Hz, respectively. Discharge rates of group IV afferent fibers
      were significantly lower than those of groups I, II and III afferents. It was
      concluded that manual acupuncture needle stimulation to the hindlimbs activated
      afferent nerve fibers belonging to all four groups of afferents in rats. It is
      suggested that all four groups of somatic afferents activated by manual
      acupuncture stimulation will elicit various effects when action potentials are
      delivered to the central nervous system.

PMID- 15992455
TI  - Prostate-specific antigen endpoints in hormone-refractory prostate cancer.

PMID- 15992456
TI  - Highlights from the 41st Annual Meeting of the American Society of Clinical
      Oncology, May 2005, and the 2005 American Society of Clinical Oncology Prostate
      Cancer Symposium, February 2005, Orlando, Florida.

PMID- 15992457
TI  - Patient preferences in prostate cancer: a clinician's guide to understanding
      health utilities.
AB  - Prostate cancer treatments have positive and negative outcomes that must be taken
      into account when deciding how to proceed with a patient's care. One way to
      quickly determine a patient's preferences in this situation is to ascertain their
      health utilities for various health states. Health utilities are underutilized
      but powerful tools in aiding shared decision making between patients and
      physicians. This review is intended to inform physicians about the different
      techniques available, help the physician choose among them, and aid initial
      development of utilities for use in the clinic by way of the tables' references.
      A brief history, summary of applications and current directions of health
      utilities, and collection of references are provided to increase the reader's
      overall knowledge of health utilities and encourage their use in the clinic.
      Ultimately, the use and choice of one of these direct preference-based measures
      depends on the needs of the physician.

PMID- 15992458
TI  - The "emigration, migration, and immigration"of prostate cancer.
AB  - In the vast majority of cases, cancer continues to be an incurable disease when
      it has spread beyond the primary organ. Most cancer research and therapy design
      to date has focused on chemotherapy directed at killing the replicating tumor
      cells. Little attention has been placed on targeting the microenvironments of the
      primary tumor site, the circulating tumor cells, or the metastatic or secondary
      (target) tumor site and how cancer cells move among them. To develop these
      targets, a better understanding of metastasis and the mechanisms underlying the
      spread of tumors is required. This review describes the steps of metastasis using
      a paradigm of emigration to migration to immigration, with prostate cancer as a
      model system.

PMID- 15992459
TI  - Clinical benefit of zoledronic acid for the prevention of skeletal complications
      in advanced prostate cancer.
AB  - Men with prostate cancer are at high risk of developing bone metastases that can
      lead to clinically significant skeletal morbidity. Recently, a randomized,
      placebo-controlled, phase III trial in 422 men with hormone-refractory prostate
      cancer and bone metastases demonstrated that zoledronic acid (4 mg every 3 weeks)
      significantly reduced the incidence and onset of skeletal complications and
      provided significant long-term reductions in bone pain compared with placebo.
      Patients received zoledronic acid for a 15-month core phase, with the option to
      continue therapy for 9 more months on the extension phase. To evaluate the
      continuing benefit of long-term zoledronic acid therapy, retrospective
      exploratory analyses were conducted based on the incidence of skeletal-related
      events (SREs; defined as pathologic bone fracture, spinal cord compression,
      surgery or radiation therapy to bone, or change in antineoplastic therapy for
      bone pain) occurring only during the extension phase of this trial. Quality of
      life parameters included assessment with the Brief Pain Inventory. Similar to
      results reported for the 15-month core phase and the entire 24-month study, the 9
      month extension phase demonstrated that zoledronic acid significantly reduced the
      percentage of patients with an SRE (P = 0.017), prolonged the median time to
      first SRE (P = 0.036), reduced the annual incidence of SREs by 52% (P = 0.016),
      and reduced the risk of SREs by 53% (P = 0.022) compared with placebo.
      Furthermore, zoledronic acid was safe and well tolerated. Therefore, zoledronic
      acid provides long-term continuing clinical benefit for men with prostate cancer
      and bone metastases and represents a new therapeutic option for this population.

PMID- 15992460
TI  - Treating the biochemical recurrence of prostate cancer after definitive primary
      therapy.
AB  - As increasing numbers of men are living longer with prostate cancer, larger
      proportions will eventually present to our collective practices with increasing
      prostate-specific antigen (PSA) levels. Such PSA relapses, conservatively
      estimated to affect approximately 50,000 men each year, have become the most
      common form of advanced prostate cancer. Salvage radiation therapy and salvage
      prostatectomy have important roles in our therapeutic armamentarium and should be
      valid options for young, healthy men. Counseling patients regarding expectations
      for cancer control and treatment morbidity has become better because of reports
      from larger series of patients who have had salvage radiation therapy and
      surgery. Some patients may not be appropriate candidates for salvage local
      therapies. A growing body of evidence suggests early hormonal therapy improves
      progression-free survival (PFS) and could alter cancer-specific survival. This
      benefit seems to be greatest when hormonal therapy is initiated while PSA levels
      are low, before clinically measurable disease becomes apparent. However, there is
      a cost to be paid in side effects and health care dollars when androgen
      deprivation is administered over prolonged periods. The nonsteroidal antiandrogen
      agent bicalutamide could offer PFS equivalent to that seen with castration
      without the complications of androgen deprivation. Observational data seem to
      indicate that individuals at high risk could also receive benefit from therapy
      administered before PSA detection. The potential opportunities for novel
      therapeutic agents with low associated morbidity are great.

PMID- 15992461
TI  - Active surveillance for prostate cancer with selective delayed definitive
      therapy.
AB  - Patients diagnosed with clinically localized prostate cancer face a daunting
      variety of management choices, including conservative management, brachytherapy,
      external-beam irradiation therapy with or without neoadjuvant hormonal therapy,
      as well as surgery. As we have learned to characterize the nature of each cancer,
      we can now "risk-adjust" treatment decisions. Physicians have long sought to
      guide patients through these choices based on their best judgment about the
      threat posed by the cancer, the effectiveness of treatment, the side effects of
      therapy, and the life expectancy of the patient. Today, many patients wish to
      participate more actively in decisions about their care, weighing the risks of
      treatment-related complications and the anxiety of living with an untreated or
      uncontrolled cancer. Patient utilities measure the value patients place on a
      health state, such as living with cancer or becoming incontinent, allowing
      quantitative assessments of risks and benefits of different therapeutic options
      specific for each patient's own preferences and the nature of his cancer and life
      expectancy. As early detection programs for prostate cancer expand, men are being
      diagnosed with prostate cancer earlier in its natural history. Some of these
      cancers may not require immediate treatment but rather a period of active
      surveillance with definitive curative therapy being administered only if there
      are signs of cancer progression. This review summarizes our current understanding
      of active surveillance with selective delayed definitive therapy.

PMID- 15992462
TI  - Absence of lower urinary tract symptoms is an independent predictor for cancer at
      prostate biopsy, but prostate-specific antigen is not: results from a prospective
      series of 569 patients.
AB  - PURPOSE: Prostate needle biopsy (PNB) is the definitive method for the diagnosis
      of prostate cancer. Our objective was to evaluate prebiopsy parameters, including
      lower urinary tract symptoms, that may be predictive of positive biopsy. PATIENTS
      AND METHODS: We performed a prospective review of 569 consecutive men who
      underwent transrectal ultrasound (TRUS)-guided PNB. The prebiopsy variables
      recorded included age, prostate-specific antigen (PSA) levels, prostate volume
      (PV), percent free PSA levels, suspicious digital rectal examination (DRE)
      findings, TRUS-detected lesions, race, and American Urologic Association Symptom
      Score (AUASS). RESULTS: Low AUASS, PV, patient age, and abnormal TRUS findings
      were independent predictors of positive PNB results (P < 0.05). In patients with
      PSA levels between 4 and 10 ng/mL, the positive predictive value of a low AUASS
      (< 8) in predicting a positive PNB result is 68.7%. When race was considered
      (black vs. white), univariate analysis (UVA) indicated that race was a
      significant predictor (P = 0.034) of positive PNB. A subgroup analysis was
      performed for black men undergoing PNB (n = 256). Multivariate analysis (MVA)
      indicates that abnormal TRUS findings; low AUASS, PV, and PSA levels; and absence
      of prior biopsy are all independent predictors of PNB in the black patient group.
      A final subgroup analysis (UVA and MVA) was performed for white men (n = 310).
      Only patient age and PV demonstrated significance as independent predictors of
      PNBs in this group. CONCLUSION: This prospective analysis of 569 men demonstrates
      that traditional indicators for PNB (abnormal DRE findings and PSA levels) are
      not significant predictors of prostate cancer. Independent predictors for
      prostate included age, low AUASS, low PV, and abnormal TRUS findings. A low AUASS
      (indicative of the absence of benign disease) is an important predictor of
      prostate cancer.

PMID- 15992464
TI  - Response to docetaxel/carboplatin in patients with hormone-refractory prostate
      cancer not responding to taxane-based chemotherapy.
AB  - Few treatment options are available for patients with metastatic hormone
      refractory prostate cancer (HRPC) that is not responsive to or continues to
      progress after taxane-based chemotherapy. Although single-agent carboplatin has
      modest activity in HRPC, carboplatin chemotherapy could induce a synergistic
      effect when combined with taxanes in patients with disease resistant to taxane
      based chemotherapy. We report a case series of 4 consecutive patients treated
      with docetaxel (60-70 mg/m2) plus carboplatin (area under the curve of 4/5)
      following progression after taxane-based chemotherapy. Prostate-specific antigen
      levels decreased by > 50% in all 4 patients and were associated with improvement
      in symptoms in 3 of 4 patients. Treatment was well tolerated, with fatigue as the
      most common reported side effect. Patients received 4-11 cycles of treatment and,
      after initiation of docetaxel/carboplatin chemotherapy, survival ranged from 4.5
      months to 12 months. In this small series, there is a suggestion of a greater
      than expected response with carboplatin and docetaxel for patients who exhibit
      disease progression despite taxane-based chemotherapy or do not respond to
      therapy. A clinical trial to evaluate this effect has been initiated.

PMID- 15992463
TI  - Antigen-presenting cells 8015 (Provenge) in patients with androgen-dependent,
      biochemically relapsed prostate cancer.
AB  - BACKGROUND: Antigen-presenting cells 8015 (APC8015; Provenge) is an
      immunotherapeutic product designed to initiate a T-cell-mediated immune response
      against prostatic acid phosphatase, an antigen overexpressed in 95% of prostate
      cancer cells. In phase I/II trials, APC8015 has shown immunologic and clinical
      responses in patients with androgen-independent prostate cancer. This phase II
      trial was conducted to assess the prostate-specific antigen (PSA)-modulating
      effects of APC8015 in patients with androgen-dependent prostate cancer (ADPC)
      with biochemical progression. PATIENTS AND METHODS: Patients with nonmetastatic
      recurrent disease as manifested by increasing PSA levels (0.4-6.0 ng/mL) and who
      had undergone previous definitive surgical or radiation therapy were enrolled.
      Therapy consisted of APC8015 infusion on weeks 0, 2, and 4 (ie, 3 infusions).
      Prostate-specific antigen was measured at baseline and monthly until disease
      progression, defined as a doubling of the baseline or nadir PSA value (whichever
      was lower) to > or = 4 ng/mL or development of distant metastases. RESULTS:
      Thirteen of 18 patients demonstrated an increase in PSA doubling time (PSADT),
      with a median increase of 62% (4.9 months before treatment vs. 7.9 months after
      treatment; P = 0.09; signed-rank test). CONCLUSION: Therapy was well tolerated.
      APC8015 as single-agent immunotherapy for patients with ADPC and biochemical
      progression did not result in > or = 50% decrease in PSA from baseline levels but
      did appear to modulate PSADT in some patients. Further manipulations of host
      immunity may be required to achieve a significant antitumor effect.

PMID- 15992465
TI  - Cervical bronchogenic cysts in head and neck region.
AB  - Congenital cysts of the neck are not uncommon. Most of these are thyroglossal,
      branchial cleft and thymic cysts. Bronchogenic cysts are uncommon developmental
      anomalies of the tracheobronchial tree and rarely occur in the neck. More than 70
      cases of bronchogenic cysts in the head and neck region have been reported in the
      literature. We report three cases presenting with neck swelling in the hyoid
      region that were diagnosed as bronchogenic cysts based on clinical and
      histopathological findings.

PMID- 15992466
TI  - Conservative management of sporadic unilateral acoustic neuromas.
AB  - Our objective was to review retrospectively patients with a unilateral acoustic
      neuroma managed by observation. One hundred patients with tumours (<24 mm) were
      followed a median 25.5 months. Thirty-six acoustic neuromas grew with four growth
      patterns. No factors were associated with growth. Eighty percent of growing
      tumours grew in the first year. Eleven patients proceeded to surgery. Twenty-two
      patients were eligible for hearing preservation surgery; five of the 15 available
      for analysis subsequently lost eligibility. In conclusion, selected patients can
      be safely observed with serial imaging and follow up. Size increase in the first
      year may predict future growth. Delaying surgery until required by symptoms or
      tumour growth does not result in more morbidity for the patient. Some may lose
      the opportunity for hearing preservation surgery but operating on all would
      result in more sustaining a loss of hearing in the first few years after
      diagnosis.

PMID- 15992467
TI  - Combined Heermann and Tos (CHAT) technique in cholesteatoma surgery: surgical
      technique and preliminary results.
AB  - The combined Heermann and Tos (CHAT) technique is the combination of Heermann's
      'cartilage palisade tympanoplasty' and Tos's 'modified combined approach
      tympanoplasty = modified intact canal wall mastoidectomy'. The first author (Cem
      Uzun) performed the CHAT technique as a one-stage operation in 15 ears of 15
      patients with cholesteatoma. Two patients (one with a follow up of less than six
      months and one who did not show up at the final re-evaluation) were excluded from
      the study. Median age in the remaining 13 patients was 37 years (range: 14-57
      years). Cholesteatoma type was attic, sinus (Tos tensa type 1) and tensa
      retraction (Tos tensa type 2) in six, five and two ears, respectively.
      Cholesteatoma stage was Saleh and Mills stage 1, 2, 3, 4 and 5 in one, three,
      four, four and one ear, respectively. The eustachian tube was not involved with
      cholesteatoma in any ear. After drilling of the superoposterior bony annulus,
      transcanal atticotomy with preservation of thin bridge and cortical mastoidectomy
      with intact canal wall, the cholesteatoma was removed, and the eardrum and
      atticotomy were reconstructed with palisades of auricular cartilage. Type I
      tympanoplasty was performed in two ears, type II in nine ears and type III
      (stapes absent) in two ears, with either autologous incus (eight cases), cortical
      bone (two) or auricular cartilage (one). No complication occurred before, during
      or after surgery. Oto-microscopy and audiometry were done before and at a median
      of 13 months after surgery (mean 14 months, range 7-30 months). There was no sign
      of residual or recurrent cholesteatoma in any patient during the follow-up
      period. At the final examination, all ears were dry and had an intact eardrum
      except one with a small, central hole, which had been seen since the early post
      operative period. Clean and stable attic retraction with a wide access was
      observed in two ears. Post-operative hearing at the final evaluation was better
      (change > 10 dB) than the pre-operative one in nine ears and did not change in
      the remaining four. Pre- and post-operative mean hearing values were, pure-tone
      average 47 and 35 dB (p = 0.01) and air-bone gap 30 and 20 dB (p = 0.02),
      respectively. With the CHAT technique, cholesteatoma can be completely and safely
      removed from the middle ear, and a durable and resistant reconstruction of the
      middle ear with reasonable hearing can be achieved. However, a further study
      should analyse long-term results of a larger patient group.

PMID- 15992468
TI  - Matrix metalloproteinases and their inhibitors in non-neoplastic
      otorhinolaryngological disease.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent
      endopeptidases that play a key role in extracellular matrix (ECM) degradation.
      MMPs are known to be important in normal remodelling processes. Overexpression
      and activation of MMPs or an imbalance of active MMPs and tissue inhibitors of
      metalloproteinases (TIMPs) has been linked with a number of specific disease
      states associated with the breakdown and remodelling of the extracellular matrix.
      MMPs and TIMPs play a role in the development and progression of conditions such
      as acute and chronic otitis media, nasal polyposis and Sjogren's disease of
      salivary glands. Their role in allergic rhinitis has not been proven although
      they do appear to have a role in asthma, a condition closely linked to rhinitis.
      The use of a broad spectrum MMP inhibitor has been shown to alter the outcome of
      acute otitis media and otitis media with effusion. Therapeutic strategies with
      anti-MMP molecules are currently being developed and may play a role in
      modulating the course of non-neoplastic otorhinolaryngological disease in the
      future.

PMID- 15992469
TI  - Scintigraphic evaluation of nasal mucociliary activity in unilateral chronic
      otitis media.
AB  - Mucociliary clearance is a key defence mechanism in human upper and lower
      airways. Although mucociliary activity is present in both ears of the patients,
      most cases of chronic otitis media are unilateral. In this study, we aim to
      evaluate the difference between nasal mucociliary activity of the affected and
      non-affected sides in patients with unilateral chronic otitis media. Both nasal
      transport times of 36 patients with unilateral chronic otitis media were compared
      statistically with each other and with the control group by independent samples t
      test. The nasal mucociliary transport times of the nasal cavity at the same side
      as the affected ear and as the non-affected ear are significantly different, in
      the same patients. Our study shows that impaired or decreased nasal mucociliary
      activity may result in dysfunction of the eustachian tube and middle-ear ciliary
      activity, which plays an important role in the aetiopathogenesis of chronic
      otitis media.

PMID- 15992470
TI  - Does passive smoking affect the outcome of grommet insertion in children?
AB  - Bilateral myringotomy with insertion of ventilation tube (grommet) is the most
      common surgical procedure done on children under general anaesthetic. A
      prospective study was conducted on children undergoing grommet insertion to
      ascertain any relationship between exposures of passive smoking to the outcome of
      grommet insertion. Six hundred and six children (with 1174 ears) who underwent
      grommet insertion for recurrent secretory otitis media were followed up till the
      grommets were extruded. Thirty-three children (65 per cent), whose mothers smoked
      when they were pregnant, had bilateral narrow external ear canals. The median
      survival rate of grommet was 59 weeks in children who were exposed to passive
      smoking as compared to 86 weeks for non-exposed children and the extrusion rate
      of grommet was 36 per cent higher at the end of one year if both parents smoked
      compared to the non-smoking group. Post-extrusion myringosclerosis was 64 per
      cent if both parents smoked and less than 20 per cent if neither parents smoked.
      It is concluded that post-operative infection rate, attic retraction, post
      extrusion myringosclerosis and permanent perforations of tympanic membrane were
      more common in children exposed to passive smoking. The study provides further
      support to professional and governmental advice that passive smoking is harmful.

PMID- 15992471
TI  - Co-morbidity of migraine and Meniere's disease -- is allergy the link?
AB  - This study determined the prevalence of migraine and allergy in patients with
      Meniere's disease (MD) compared with age- and sex-matched controls. We tested the
      hypothesis that if migraine and MD is linked by allergy, then allergy should be
      more prevalent in patients with MD and migraine compared with MD patients without
      migraine. A web-based questionnaire was used to recruit patients with MD (n =
      108) while the control group consisted of patients attending the ENT clinic for
      other problems (n = 100). The prevalence of migraine and allergy was
      significantly higher in patients with MD compared with age- and sex-matched
      controls (p > or = 0.005). In addition, the prevalence of allergy was
      significantly higher in patients who had both MD and migraine (30/42) than MD
      alone (26/66,p = 0.002). However, there was no link with any specific allergy
      types. This study suggests that migraine and MD may be linked by an immunological
      determinant.

PMID- 15992472
TI  - Accuracy of finger-tip palpated tracheostomy tube cuff pressure readings among
      otolaryngologists.
AB  - The tracheal mucosa is very a delicate structure, and pressure-ischaemia problems
      following the use of cuffed tracheostomy tubes are well documented. Iatrogenic
      tracheal stenosis is one of the consequences of mucosal ischaemia and is very
      difficult to treat. In this study the accuracy of finger-tip tested tracheostomy
      tube cuff inflation pressure, as judged by consultants and non-consultants, was
      assessed by comparison with manometric pressure readings. The estimated pressure
      readings from the consultant group were more accurate than those from the non
      consultant group, but a high standard deviation and very big difference between
      low and high readings in both these groups showed the real extent of the problem.
      Participants who performed 10 or more tracheostomies a year obtained more
      accurate results. No definite correlation was observed between the readings and
      the experience of the participants in otolaryngology or the size of the tube
      used. The authors recommend that instrumental monitoring of cuff pressure be
      considered good practice among junior otolaryngologists.

PMID- 15992473
TI  - Use of an ophthalmic knife for middle-ear microsurgery.
AB  - Traditionally, micro-scissors, hooks, sickle knives and needles are used in the
      ear for the dissection and release of fibrous adhesions. The major limitation of
      these instruments is that they are often bent or blunt, as they are reusable. We
      describe an ophthalmic knife that offers precision in middle-ear microsurgery.

PMID- 15992474
TI  - Post-operative adjuvant chemoradiotherapy with carboplatin and 5-fluorouracil for
      primary branchiogenic carcinoma.
AB  - BACKGROUND: Branchiogenic carcinoma occurs only rarely. A pathologic description
      and post-operative adjuvant therapy with carboplatin (CBDCA) and daily oral 5
      fluorouracil (UFT) are analysed. CASE REPORT: We present the case of a 52-year
      old man with a lateral neck mass lesion. A fine-needle aspiration was performed
      and cytological examination showed class IV disease. The patient underwent
      excision of the mass and an intra-operative rapid pathological diagnosis of
      squamous cell carcinoma was made; we then went on to perform neck dissection. The
      patient received post-operative radiation therapy (total 64 Gy) and chemotherapy
      (CBDCA 100 mg/week and UFT 300 mg/day). He was followed up for 62 months after
      surgery without any evidence of recurrence of cancer. CONCLUSION: This case
      satisfies the histological criteria established by Martin and Khafif for a
      primary branchiogenic carcinoma. The management would be wide surgical excision
      of the tumour, including neck dissection, followed by adjuvant therapy, such as
      chemoradiation. As post-operative adjuvant therapy for primary branchiogenic
      carcinoma, chemoradiotherapy with carboplatin and UFT was a safe and well
      tolerated regimen.

PMID- 15992475
TI  - Brown-Vialetto-Van Laere syndrome: a rare syndrome in otology.
AB  - Brown-Vialetto-Van Laere syndrome, or pontobulbar palsy with deafness, is a rare
      disorder characterized by bilateral sensorineural deafness and a variety of
      cranial nerve disorders usually involving the motor components of the lower
      cranial nerves. Less commonly, spinal motor nerves and upper motor neurons are
      involved. Familial and sporadic cases have been reported. Based on evidences,
      this syndrome has been related to autosomal recessive, autosomal dominant and X
      linked inheritance. Autoimmune origin has been considered as well. In this paper,
      we report the case of a 38-year-old female patient who primarily presented with
      bilateral sensorineural hearing loss and then progressively developed Xth and
      VIIth cranial nerve paralysis. Brown-Vialetto-Van Laere syndrome was diagnosed
      with this symptom complex of sensorineural hearing loss and pontobulbar palsy.

PMID- 15992476
TI  - Congenital stapes footplate fixation associated with duplication of lobule.
AB  - We report the case of an 18-year-old male patient who presented to us with
      unilateral conductive hearing loss with duplication of the lobule. An exploratory
      tympanotomy revealed stapes footplate fixation. A stapedotomy with insertion of a
      Teflon piston was performed with improvement in his hearing. We believe this is
      the first reported case of such an abnormality.

PMID- 15992477
TI  - Respiratory epithelial adenomatoid hamartoma in the nasopharynx.
AB  - We present a case report of a female patient with complaints of single-sided
      nasal obstruction. A polypoid structure was seen in the nasopharynx. Histologic
      examination showed a respiratory epithelial adenomatoid hamartoma -- a rare,
      benign lesion. Therapy consisted of complete excision. In line with previous
      reports, the lesion did not recur during 13 months of follow up. The clinical and
      pathological features of this abnormality are discussed.

PMID- 15992478
TI  - Two stage management of petrositis with associated mycotic aneurysm of the
      intrapetrous carotid artery.
AB  - Mycotic aneurysm of the petrous temporal bone is extremely rare, with only 12
      cases previously reported. We review the literature to date and present a case of
      petrositis complicated by a mycotic aneurysm of the internal carotid artery,
      which was managed by endovascular balloon occlusion and subsequent total
      petrosectomy. We can find no other case in the literature where balloon occlusion
      has been used to treat a mycotic aneurysm of the intrapetrous carotid artery
      prior to total petrosectomy to treat petrositis.

PMID- 15992479
TI  - Asymptomatic oropharyngeal lipoma complicating intubation.
AB  - Oropharyngeal lipomas are rare tumours. We present the case of a young man with
      an asymptomatic lipoma almost completely occluding his supraglottic airway, found
      on magnetic resonance imaging (MRI) for a separate oral cavity lesion. Pre
      operative anaesthetic assessment was undertaken because of the risk of airway
      obstruction at induction of general anaesthesia. We discuss the awake fibre-optic
      technique used for induction, as well as the treatment and follow-up of these
      tumours. This case highlights the need for formal anaesthetic assessment, in such
      cases, to avoid total airway obstruction at induction of general anaesthesia. It
      also emphasizes the extent of supraglottic obstruction that can be present
      without giving rise to any symptoms.

PMID- 15992480
TI  - Intracranial tuberculoma -- a diagnostic dilemma.
AB  - The characteristics of intracranial tuberculoma on computed tomography (CT) and
      magnetic resonance imaging (MRI) are not well known. The authors present a
      patient with an intracranial tuberculoma in whom the diagnosis was confirmed only
      after surgical excision.

PMID- 15992481
TI  - Bilateral objective tinnitus secondary to congenital middle-ear myoclonus.
AB  - Subjective tinnitus (heard only by the patient) is a common otological complaint.
      Objective tinnitus (heard by the examiner as well as the patient) is extremely
      rare. There are only a few cases of objective tinnitus, secondary to middle-ear
      myoclonus, described in the literature. We present the case of a child with
      bilateral, congenital, objective tinnitus, secondary to middle-ear myoclonus,
      with otherwise normal hearing thresholds (250 Hz-8 kHz), and with no evidence of
      intra-cerebral or systemic disorders. No similar case has been reported in the
      world literature.

PMID- 15992482
TI  - Tophaceous gout presenting as a dorsal nasal lump.
AB  - A literature review reveals that gout has been described as affecting many sites
      in the head and neck region, both in the arthritic and tophaceous form. Gout can
      often mimic malignancy or infection, and has been described as causing acute
      airway problems requiring emergency tracheotomy. Here we describe the first
      published case of tophaceous gout affecting the soft tissues overlying the nasal
      bones. The patient presented with a bony, hard, dorsal hump and requested
      aesthetic rhinoplasty. We also describe an endoscopic technique for removal of
      tophi using a powered microdebrider system with a protected burr head. Endoscopic
      powered microdebrider blade excision of tophi affecting the limbs has already
      been described, with reduced complications when compared with conventional
      curettage and debridement techniques. This is the first such application to the
      nose.

PMID- 15992483
TI  - Aneurysmal bone cyst of the spine.
AB  - The authors present the case of an 11-year-old boy with a painful, rapidly
      expanding lesion in the posterior triangle of the neck. There was no history of
      cervical trauma. Computerized tomography of the neck revealed a unicameral
      (single-chambered) aneurysmal bone cyst involving the C3 vertebra. Treatment was
      by open resection and curettage; no recurrence was seen at six months. We discuss
      the natural history, differential diagnosis, radiographic appearance and
      treatment modalities for this unusual, benign, expanding, osteolytic lesion
      containing blood-filled cystic cavities.

PMID- 15992484
TI  - Mucin-secreting papillary adenocarcinoma of the hyoid bone: a unique case.
AB  - We present a unique case of a mucin-secreting papillary adenocarcinoma of
      intestinal type which has invaded and completely destroyed the hyoid bone and
      metastasized to the cervical lymph nodes bilaterally. The tumour is believed to
      have originated from a malignant thyroglossal duct remnant, and was managed with
      surgery and radiotherapy. We describe the case and discuss the literature
      regarding hyoid bone tumours.

PMID- 15992485
TI  - The cocktail party problem.
AB  - This review presents an overview of a challenging problem in auditory perception,
      the cocktail party phenomenon, the delineation of which goes back to a classic
      paper by Cherry in 1953. In this review, we address the following issues: (1)
      human auditory scene analysis, which is a general process carried out by the
      auditory system of a human listener; (2) insight into auditory perception, which
      is derived from Marr's vision theory; (3) computational auditory scene analysis,
      which focuses on specific approaches aimed at solving the machine cocktail party
      problem; (4) active audition, the proposal for which is motivated by analogy with
      active vision, and (5) discussion of brain theory and independent component
      analysis, on the one hand, and correlative neural firing, on the other.

PMID- 15992486
TI  - Analyzing functional connectivity using a network likelihood model of ensemble
      neural spiking activity.
AB  - Analyzing the dependencies between spike trains is an important step in
      understanding how neurons work in concert to represent biological signals.
      Usually this is done for pairs of neurons at a time using correlation-based
      techniques. Chornoboy, Schramm, and Karr (1988) proposed maximum likelihood
      methods for the simultaneous analysis of multiple pair-wise interactions among an
      ensemble of neurons. One of these methods is an iterative, continuous-time
      estimation algorithm for a network likelihood model formulated in terms of
      multiplicative conditional intensity functions. We devised a discrete-time
      version of this algorithm that includes a new, efficient computational strategy,
      a principled method to compute starting values, and a principled stopping
      criterion. In an analysis of simulated neural spike trains from ensembles of
      interacting neurons, the algorithm recovered the correct connectivity matrices
      and interaction parameters. In the analysis of spike trains from an ensemble of
      rat hippocampal place cells, the algorithm identified a connectivity matrix and
      interaction parameters consistent with the pattern of conjoined firing predicted
      by the overlap of the neurons' spatial receptive fields. These results suggest
      that the network likelihood model can be an efficient tool for the analysis of
      ensemble spiking activity.

PMID- 15992487
TI  - Data-robust tight lower bounds to the information carried by spike times of a
      neuronal population.
AB  - We develop new data-robust lower-bound methods to quantify the information
      carried by the timing of spikes emitted by neuronal populations. These methods
      have better sampling properties and are tighter than previous bounds based on
      neglecting correlation in the noise entropy. Our new lower bounds are precise
      also in the presence of strongly correlated firing. They are not precise only if
      correlations are strongly stimulus modulated over a long time range. Under
      conditions typical of many neurophysiological experiments, these techniques
      permit precise information estimates to be made even with data samples that are
      three orders of magnitude smaller than the size of the response space.

PMID- 15992488
TI  - Fluctuation-dissipation theorem and models of learning.
AB  - Advances in statistical learning theory have resulted in a multitude of different
      designs of learning machines. But which ones are implemented by brains and other
      biological information processors? We analyze how various abstract Bayesian
      learners perform on different data and argue that it is difficult to determine
      which learning-theoretic computation is performed by a particular organism using
      just its performance in learning a stationary target (learning curve). Based on
      the fluctuation-dissipation relation in statistical physics, we then discuss a
      different experimental setup that might be able to solve the problem.

PMID- 15992489
TI  - Correlated firing in a feedforward network with Mexican-hat-type connectivity.
AB  - We report on deterministic and stochastic evolutions of firing states through a
      feedforward neural network with Mexican-hat-type connectivity. The prevalence of
      columnar structures in a cortex implies spatially localized connectivity between
      neural pools. Although feedforward neural network models with homogeneous
      connectivity have been intensively studied within the context of the synfire
      chain, the effect of local connectivity has not yet been studied so thoroughly.
      When a neuron fires independently, the dynamics of macroscopic state variables (a
      firing rate and spatial eccentricity of a firing pattern) is deterministic from
      the law of large numbers. Possible stable firing states, which are derived from
      deterministic evolution equations, are uniform, localized, and nonfiring. The
      multistability of these three states is obtained where the excitatory and
      inhibitory interactions among neurons are balanced. When the presynapse-dependent
      variance in connection efficacies is incorporated into the network, the variance
      generates common noise. Then the evolution of the macroscopic state variables
      becomes stochastic, and neurons begin to fire in a correlated manner due to the
      common noise. The correlation structure that is generated by common noise
      exhibits a nontrivial bimodal distribution. The development of a firing state
      through neural layers does not converge to a certain fixed point but keeps on
      fluctuating.

PMID- 15992490
TI  - Supervised learning in a recurrent network of rate-model neurons exhibiting
      frequency adaptation.
AB  - For gradient descent learning to yield connectivity consistent with real
      biological networks, the simulated neurons would have to include more realistic
      intrinsic properties such as frequency adaptation. However, gradient descent
      learning cannot be used straightforwardly with adapting rate-model neurons
      because the derivative of the activation function depends on the activation
      history. The objectives of this study were to (1) develop a simple computational
      approach to reproduce mathematical gradient descent and (2) use this
      computational approach to provide supervised learning in a network formed of rate
      model neurons that exhibit frequency adaptation. The results of mathematical
      gradient descent were used as a reference in evaluating the performance of the
      computational approach. For this comparison, standard (nonadapting) rate-model
      neurons were used for both approaches. The only difference was the gradient
      calculation: the mathematical approach used the derivative at a point in weight
      space, while the computational approach used the slope for a step change in
      weight space. Theoretically, the results of the computational approach should
      match those of the mathematical approach, as the step size is reduced but
      floating-point accuracy formed a lower limit to usable step sizes. A systematic
      search for an optimal step size yielded a computational approach that faithfully
      reproduced the results of mathematical gradient descent. The computational
      approach was then used for supervised learning of both connection weights and
      intrinsic properties of rate-model neurons to convert a tonic input into a phasic
      tonic output pattern. Learning produced biologically realistic connectivity that
      essentially used a monosynaptic connection from the tonic input neuron to an
      output neuron with strong frequency adaptation as compared to a complex network
      when using nonadapting neurons. Thus, more biologically realistic connectivity
      was achieved by implementing rate-model neurons with more realistic intrinsic
      properties. Our computational approach could be applied to learning of other
      neuron properties.

PMID- 15992491
TI  - Learning bounds for kernel regression using effective data dimensionality.
AB  - Kernel methods can embed finite-dimensional data into infinite-dimensional
      feature spaces. In spite of the large underlying feature dimensionality, kernel
      methods can achieve good generalization ability. This observation is often
      wrongly interpreted, and it has been used to argue that kernel learning can
      magically avoid the "curse-of-dimensionality" phenomenon encountered in
      statistical estimation problems. This letter shows that although using kernel
      representation, one can embed data into an infinite-dimensional feature space;
      the effective dimensionality of this embedding, which determines the learning
      complexity of the underlying kernel machine, is usually small. In particular, we
      introduce an algebraic definition of a scale-sensitive effective dimension
      associated with a kernel representation. Based on this quantity, we derive upper
      bounds on the generalization performance of some kernel regression methods.
      Moreover, we show that the resulting convergent rates are optimal under various
      circumstances.

PMID- 15992492
TI  - Shaping sands, shifting services.

PMID- 15992493
TI  - Implementing electronic medical record systems in developing countries.
AB  - The developing world faces a series of health crises including HIV/AIDS and
      tuberculosis that threaten the lives of millions of people. Lack of
      infrastructure and trained, experienced staff are considered important barriers
      to scaling up treatment for these diseases. In this paper we explain why
      information systems are important in many healthcare projects in the developing
      world. We discuss pilot projects demonstrating that such systems are possible and
      can expand to manage hundreds of thousands of patients. We also pass on the most
      important practical lessons in design and implementation from our experience in
      doing this work. Finally, we discuss the importance of collaboration between
      projects in the development of electronic medical record systems rather than
      reinventing systems in isolation, and the use of open standards and open source
      software.

PMID- 15992494
TI  - Adoption and perception of electronic clinical communications in Scotland.
AB  - OBJECTIVES: To determine the uptake of multiple eHealth facilities enabled by the
      NHS Scotland Electronic Clinical Communications Implementation Programme (ECCI)
      and to ascertain primary and secondary care users' perceptions. DESIGN:
      Prospective monthly measurement of 37 indicators of roll-out and adoption.
      Retrospective questionnaire survey of users. SETTING: Scottish health board
      regions. Quantitative implementation indicators were gathered in primary and
      secondary care across all 16 regions. Questionnaire data were obtained from
      recorded users in five representative regions (112 general practices, 92
      secondary care units). OUTCOME MEASURES: Change in uptake levels of ECCI
      facilities over a 15-month period. Users' perceptions of benefits, facilitators
      and barriers. RESULTS: All health boards participated in the monthly data set
      collection. The response rate to the survey was 62% in primary care and 37% in
      secondary care. Across Scotland as a whole, the process of implementation was
      gradual. While there were marked gains in the availability of ECCI facilities
      over the observation period, rates of adoption lagged behind and varied across
      alternative facilities. Electronic results were widely used, with most
      laboratories offering them and around half of general practices receiving them.
      More modest rates of adoption were observed for e-discharge letters, e-referrals,
      e-clinic letters and clinical e-mail. E-booking was used very little. Among
      engaged users responding to the survey, electronic access to test results was the
      most frequently utilised facility and electronic outpatient booking the least.
      Perceived benefits of ECCI facilities included convenience, ease of use, time
      saving and provision of an audit trail. Perceived barriers included the need to
      duplicate data entry where new systems were not universally implemented,
      technological difficulties, time, training and resources. CONCLUSIONS:
      Significant progress was observed in the implementation of ECCI facilities across
      Scotland. Users reported that these improved communication and were beneficial,
      but system reliability, incompatibility and duplication of data hindered more
      widespread uptake. Data were collected at a transitional phase of the programme.
      Whilst, among users of ECCI facilities, perceptions of the programme and its
      potential benefits were generally positive, its full impact will not become
      evident until the new electronic tools are implemented nationally and have been
      more fully integrated into normal work routines.

PMID- 15992495
TI  - Implementing the National Programme for IT: what can we learn from the Scottish
      experience?
AB  - The National Programme for IT (NPfIT) promises to revolutionize the delivery of
      health care by enabling seamless and secure electronic exchange of clinical
      information within the NHS. Challenges to NPfIT highlighted in the media and
      academic commentary are common to such initiatives worldwide. This paper offers
      key messages and recommendations derived from a comparable electronic clinical
      communications programme in Scotland, and elsewhere, as a means to aid the
      implementation process.

PMID- 15992496
TI  - Information communications technology in general practice: cross-sectional survey
      in London.
AB  - OBJECTIVE: To determine the prevalence of use of a range of information and
      communications technology (ICT) applications in general practice in London, UK.
      DESIGN: Cross-sectional postal questionnaire study. PARTICIPANTS: 996 general
      practitioners (GPs) working in 32 primary care trusts (PCTs) in London. MAIN
      OUTCOME MEASURES: Rates of self-reported use of paperless, paper-light and paper
      based consultations in general practice, perceived barriers and facilitating
      factors relating to their use and current use or interest in using innovative
      ICT. RESULTS: Questionnaires from 520 respondents (52%) were analysed. A computer
      was used in clinical consultations by 95% of respondents; 34% operated paper
      light consultations, and 41% paperless consultations. An electronic record was
      always used in 76% of consultations and paper records were never used in 19%.
      Paper-light and paperless consultations were conducted more frequently in larger
      practices and those in more affluent PCTs. Numerous barriers to the
      implementation of ICT were identified, including lack of time, lack of training
      resources and negative attitudes to computers. Personal digital assistants were
      used by 18% of respondents and 72% were interested in their use in the future.
      CONCLUSION: We have shown that there has been a considerable increase in the rate
      of use of ICT in general practice in recent years, but these rates have fallen
      behind targets set by the NHS IT Strategy. Numerous barriers to the
      implementation of ICT exist, and further research is needed into means of
      overcoming them and on the evaluation of computer-supported consultations and
      other technologies in primary care.

PMID- 15992497
TI  - Seniors' views on the use of electronic health records.
AB  - In the Mauricie and Centre-du-Quebec region of the province of Quebec, Canada, an
      integrated services network has been implemented for frail seniors. It combines
      three of the best practices in the field of integrated services, namely: single
      entry point, case management and personalized care plan. A shared
      interdisciplinary electronic health record (EHR) system was set up in 1998. A
      consensus on the relevance of using EHRs is growing in Quebec, in Canada and
      around the world. However, technology has out-paced interest in the notions of
      confidentiality, informed consent and the impact perceived by the clientele. This
      study specifically examines how frail seniors perceive these issues related to an
      EHR. The conceptual framework is inspired by the DeLone and McLean model whose
      main attributes are: system quality, information quality, utilisation modes and
      the impact on organisations and individuals. This last attribute is the focus of
      this study, which is a descriptive with quantitative and qualitative component.
      Thirty seniors were surveyed. Positive information they provided falls under
      three headings: (i) being better informed; (ii) trust and consideration for
      professionals; and (iii) appreciation of innovation. The opinions of the seniors
      are generally favourable regarding the use of computers and the EHR in their
      presence. Improvements in EHR systems for seniors can be encouraged.

PMID- 15992498
TI  - Computer visualisation of patient safety in primary care: a systems approach
      adapted from management science and engineering.
AB  - Patient safety and medical errors in ambulatory primary care are receiving
      increasing attention from policy makers, accreditation bodies and researchers, as
      well as by practising family physicians and their patients. While a great deal of
      progress has been made in understanding errors in hospital settings, it is
      important to recognise that ambulatory settings pose a very large and different
      set of challenges and that the types of hazards that exist and the strategies
      required to reduce them are very different. What is needed is a logical
      theoretical model for understanding the causes of errors in primary care, the
      role of healthcare systems in contributing to errors, the propagation of errors
      through complex systems and, importantly, for understanding ambulatory primary
      care in the context of the larger healthcare system. The authors have developed
      such a model using a formal 'systems engineering' approach borrowed from the
      management sciences and engineering. This approach has not previously been
      formally described in the medical literature.This paper outlines the formal
      systems approach, presents our visual model of the system, and describes some
      experiences with and potential applications of the model for monitoring and
      improving safety. Applications include providing a framework to help focus
      research efforts, creation of new (visual) error reporting and taxonomy systems,
      furnishing a common and unambiguous vision for the healthcare team, and
      facilitating retrospective and prospective analyses of errors and adverse events.
      It is aimed at system redesign for safety improvement through a computer-based
      patient-centred safety enhancement and monitoring instrument (SEMI-P). This model
      can be integrated with electronic medical records (EMRs).

PMID- 15992499
TI  - A framework for mobile healthcare answers to chronically ill outpatient non
      adherence.
AB  - Non-adherence (also known as 'non-compliance') is a major barrier undermining
      healing efforts within out-of-hospital self-management programmes, resulting in
      waste of human and social resources. This study suggests a theoretical framework
      of activities through which mobile patient solutions might address non-adherence
      determinants in a broader context of clinical interventions. The goal of the
      paper is to explore a dilemma associated with such interventions: the uncertainty
      regarding the level of patient involvement and technology support. We follow a
      critical orientation approach in discussing this multi-faceted conundrum: we
      summarise the latest vision on adherence factors, we suggest several types of
      interventions through which mobile healthcare solutions could address them, and
      we explore in detail the dilemma of patient and technology roles. We conclude
      that there is no universally optimal solution, and practical conditions depending
      on patient, disease, treatment and healthcare system are determining factors in
      prescribing the level of patient involvement and technology support. Our work is
      intended to stimulate further research into the nature of mobile solutions in
      health care and, especially, into patient acceptance aspects, in an endeavour to
      contribute to improving adherence with minimum obtrusiveness.

PMID- 15992500
TI  - A knowledge management-based intranet: asset or EBM liability?
AB  - This paper summarises the presentation given at the British Computer Society
      Primary Health Care Specialist Group annual conference 2004. It outlines the four
      years of experience gained in implementing a knowledge management-based intranet
      across a local health community. Consideration is given to definitions of
      knowledge management and evidence-based medicine. The paper outlines the
      potential impacts and actual results over the four-year period, with reference to
      the wider issues involved.

PMID- 15992509
TI  - History and development of plant sterol and stanol esters for cholesterol
      lowering purposes.
AB  - Plant stanol esters provide a novel approach to lowering plasma low-density
      lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by
      a long period of research into the cholesterol-lowering properties of plant
      sterols and, recently, plant stanols. Both classes of compound competitively
      inhibit the absorption of cholesterol and thus lower its level in plasma. Initial
      impressions were that stanols were more effective and safer than sterols, but the
      negative outcome of a study led to the recognition that the lipid solubility of
      free stanols was very limited. This was overcome by esterifying them with fatty
      acids, with the resultant stanol esters being freely soluble in fat spreads. This
      led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995.
      The coincident publication of the year-long North Karelia study conclusively
      demonstrated the long-term LDL-lowering efficacy of plant stanol esters.
      Variables that might influence the efficacy of stanol esters include dose,
      frequency of administration, food vehicle in which the stanol ester is
      incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed
      as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol
      by 6% to 15%. This effect is maintained, appears to be similar with once-daily or
      divided dosage, and is independent of the fat content of the food vehicle. Short
      term studies suggest that equivalent amounts of plant sterol and stanol esters
      are similarly effective in lowering LDL, the main difference being that plasma
      plant sterol levels increase on plant sterols and decrease on plant stanols. The
      clinical significance of these changes remains to be determined.

PMID- 15992510
TI  - Cholesterol and plant sterol absorption: recent insights.
AB  - The recent discovery of transporters in the intestinal mucosa and the canalicular
      membrane has given new insights into the regulation of intestinal absorption as
      well as the biliary output of cholesterol and plant sterols. The 2 adenosine
      triphosphate (ATP)-binding cassette (ABC) half-transporters ABCG5 and ABCG8 are
      expressed in the mucosa cells and the canalicular membrane, and they resecrete
      sterols, especially absorbed plant sterols, back into the intestinal lumen and
      from the liver into bile. Defects of either of these cotransporters lead to the
      rare inherited disease of phytosterolemia, which is clinically defined by
      hyperabsorption and diminished biliary excretion of plant sterols. Furthermore,
      it has been recently demonstrated that the Niemann-Pick C1-Like 1 (NPC1L1)
      transporter is most likely responsible for the transport of cholesterol and plant
      sterols from the brush border membrane into the intestinal mucosa. Ezetimibe
      interferes with NPC1L1, reducing the intestinal uptake of cholesterol and plant
      sterols. These new findings contribute to our understanding of cholesterol and
      plant sterol concentrations in serum, and the effect of dietary and drug
      intervention to reduce serum concentrations of sterols.

PMID- 15992511
TI  - Plant stanol and sterol esters in the control of blood cholesterol levels:
      mechanism and safety aspects.
AB  - Incorporation of plant stanol esters into margarine is among the first examples
      of a functional food with proven low-density lipoprotein (LDL) cholesterol
      lowering effectiveness. Recently, there have been many studies on the effects of
      plant stanols/sterols on cholesterol metabolism. It has been found that the serum
      LDL cholesterol-lowering effect of plant stanols/sterols originates from reduced
      intestinal cholesterol absorption, a process in which changes in micellar
      composition are thought to play a major role. However, recent findings suggest
      that there is an additional process in which plant stanols/sterols actively
      influence cellular cholesterol metabolism within intestinal enterocytes.
      Furthermore, in response to the reduced supply of exogenous cholesterol, receptor
      mediated lipoprotein cholesterol uptake is probably enhanced, as shown by
      increased LDL receptor expression. At recommended intakes of about 2 to 2.5
      g/day, products enriched with plant stanol/sterol esters lower plasma LDL
      cholesterol levels by 10% to 14% without any reported side effects. Thus, plant
      stanols/sterols can be considered to be effective and safe cholesterol-lowering
      functional food ingredients.

PMID- 15992512
TI  - Responsiveness of plasma lipids and lipoproteins to plant stanol esters.
AB  - Plant stanols have been shown to reduce serum levels of low-density lipoprotein
      (LDL) cholesterol, and they are an attractive adjunct in dietary therapy for
      elevated LDL cholesterol. This investigation addressed 3 questions through
      metabolic studies in human subjects: (1) whether plant stanol esters given at
      higher doses than the 2-g/day dose recommended by the National Cholesterol
      Education Program (NCEP) Adult Treatment Panel III (ATP III) will provide
      additional LDL-lowering efficacy (study 1); (2) whether substantial reduction in
      LDL cholesterol can be obtained in postmenopausal women with hypercholesterolemia
      by addition of plant stanol esters to the diet (study 2); and (3) whether ATP III
      goals can be obtained by adding plant stanol esters to an LDL-lowering regimen in
      high-risk patients who retain LDL cholesterol levels in the above-optimal range
      (ie, 2.6 to 3.3 mmol/L [100 to 129 mg/dL]), despite ongoing statin therapy (study
      3). Study 1 showed that maximal LDL lowering with plant stanols in the form of
      esters can be achieved at a dose of 2 g/day. Higher doses do not provide
      additional efficacy. Study 2 demonstrated that stanol esters can reduce LDL
      cholesterol levels in postmenopausal women by about 13%, which makes use of
      stanol esters attractive as a component of nondrug therapy in these women who
      generally are at relatively low risk for coronary heart disease. Finally, study 3
      found that plant stanols provide additional lowering of LDL cholesterol when
      added to ongoing statin therapy. This makes plant stanols an attractive dietary
      component to help to achieve the goals of LDL-lowering therapy in patients
      requiring an LDL-lowering drug.

PMID- 15992513
TI  - Comparison of efficacy of plant stanol ester and sterol ester: short-term and
      longer-term studies.
AB  - Published data suggest that the cholesterol-lowering effect of dietary plant
      sterol esters is less marked in longer-term than in short-term studies, whereas
      plant stanol esters maintain their efficacy. To investigate this further, healthy
      subjects and patients with familial hypercholesterolemia (FH) receiving statins
      were randomized to receive plant sterol ester 1.6 g/day or plant stanol ester 1.6
      g/day or 2.6 g/day for 2 months. There was no difference among the 3 groups in
      the pooled low-density lipoprotein (LDL)-lowering response of FH patients and
      healthy subjects, but the effect of plant sterol diminished at 2 months and was
      not significantly different from baseline. This was accompanied by increases in
      serum plant sterols and a significant decrease in 7alpha-hydroxy-4-cholesten-3
      one, a marker of bile acid synthesis, especially in FH patients not taking bile
      acid sequestrants. In contrast, plant stanol esters lowered significantly both
      LDL cholesterol and plant sterols at 2 months and had no effect on bile acid
      synthesis. Slight decreases in serum lipid-soluble antioxidants occurred with
      both plant sterol and stanol esters. Our findings suggest that absorption of
      dietary plant sterols downregulates bile acid synthesis, which attenuates their
      cholesterol-lowering efficacy. We conclude that plant stanol esters are
      preferable for the long-term management of hypercholesterolemia.

PMID- 15992514
TI  - Additive effects of plant sterol and stanol esters to statin therapy.
AB  - Plant sterol and stanol esters each have similar additive effects in lowering low
      density lipoprotein cholesterol when combined with statins. They differ in that
      plasma plant sterols increase when plant sterol esters are used for this purpose,
      especially in patients with familial hypercholesterolemia, but decrease when
      plant stanol esters are used.

PMID- 15992515
TI  - Effect of statins on noncholesterol sterol levels: implications for use of plant
      stanols and sterols.
AB  - Normal serum contains small amounts of noncholesterol sterols, including those
      reflecting cholesterol absorption and those that are markers of cholesterol
      synthesis. Absorption marker sterols include serum plant sterols, whereas
      cholesterol precursor sterols correlate with whole-body synthesis of cholesterol.
      Thus, serum noncholesterol sterols, and especially their ratios to cholesterol,
      can be used to evaluate the major features of cholesterol metabolism (ie,
      synthesis and absorption). Statin treatment reduces serum cholesterol precursors
      but increases serum plant sterols severalfold, especially in subjects with high
      absorption marker sterol levels indicative of efficient cholesterol and sterol
      absorption in general. Statin therapy is most effective in subjects with high
      serum cholesterol precursor levels. In subjects with high-absorption sterol
      markers, dietary cholesterol absorption inhibition (eg, with plant stanol and
      sterol ester margarine) needs to be combined with a statin to achieve effective
      serum cholesterol reduction. However, whereas dietary plant stanol esters reduce
      statin-induced elevations of serum plant sterol levels, serum plant sterol levels
      remain elevated during dietary plant sterol ester consumption. The clinical
      implication of high serum plant sterol levels is under active investigation.

PMID- 15992516
TI  - Stanol esters as a component of maximal dietary therapy in the National
      Cholesterol Education Program Adult Treatment Panel III report.
AB  - Use of plant stanols/sterols in forms that are sufficiently bioavailable for
      therapeutic effect should be a key element of maximal dietary therapy. This
      principle was recognized by National Cholesterol Education Program (NCEP) Adult
      Treatment Panel III (ATP III) and has been amply confirmed by experimental
      studies in humans. Since the introduction of statins, dietary therapy for control
      of elevated low-density lipoprotein (LDL) cholesterol levels has received less
      attention. The time has come, however, to reassert the importance of maximal
      dietary therapy as a cost-effective means for treatment of elevated LDL
      concentrations and for lifetime prevention of coronary heart disease.

PMID- 15992517
TI  - Low-fat formulations of plant stanols and sterols.
AB  - Clinical trials have shown that an intake of 2 to 3 g/day of esterified plant
      stanol--when incorporated in margarines or spreads--significantly reduces serum
      total and low-density lipoprotein (LDL) cholesterol concentrations without
      affecting serum high-density lipoprotein cholesterol or triglyceride levels.
      There is also a growing interest in incorporating cholesterol-lowering
      ingredients into low-fat foods. Esterification of stanols with long-chain fatty
      acids increases fat solubility by 10-fold and enables the incorporation of plant
      stanols into different food products, even low-fat foods. It provides a means of
      introducing an adequate daily amount of stanol for optimal reduction of
      cholesterol absorption, while maintaining a high-quality food product. Recent
      clinical trials show that esterified plant stanols effectively reduce serum total
      and LDL cholesterol levels, even when used in food vehicles with a low-fat
      content.

PMID- 15992518
TI  - Lack of evidence for elevated obstetric complications in childhood onset
      schizophrenia.
AB  - BACKGROUND: Pre-, peri-, and postnatal obstetric complications (OC) are reported
      to be more frequent in adult patients with schizophrenia and have been linked to
      both greater severity and to "earlier" age of onset (before either age 18 or 22)
      in studies of adult patients. We hypothesized that by extrapolation, patients
      with childhood-onset schizophrenia (COS), with very early onset and very severe
      illness, would have had more numerous or more salient OC compared with their
      healthy siblings. METHODS: We compared the obstetric records of 60 COS children
      and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a
      comprehensive measurement scale consisting of 37 variables having included a
      separate scale for fetal hypoxia. RESULTS: Patients with COS did not have a
      higher incidence of OC than the healthy sibling control group with the exception
      of increased incidence of maternal vomiting. CONCLUSIONS: Obstetric
      complications, with the possible exception of maternal vomiting, are unlikely to
      play a major role in the etiopathogenesis of childhood-onset schizophrenia.

PMID- 15992519
TI  - MLC1 gene is associated with schizophrenia and bipolar disorder in Southern
      India.
AB  - BACKGROUND: Chromosome 22q13 has shown linkage with schizophrenia (SCZ) and
      bipolar affective disorder (BPAD). A missense mutation in MLC1 (putative cation
      channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has
      been reported. We have investigated the relationship of MLC1 with SCZ and BPAD in
      Southern India. METHODS: All exons and flanking intronic sequences of MLC1 were
      screened for novel variations. Case-control (216 BPAD, 193 SCZ, 116 control
      subjects) and family-based analyses (113 BPAD, 107 SCZ families) were performed
      to evaluate association of MLC1 with these disorders. RESULTS: We found 33 MLC1
      sequence variations, including three novel mutations: Val210Ile, Leu308Gln, and
      Arg328His in six BPAD cases and Val210Ile in one control individual. Minor allele
      of a common variation, ss16339182 (in approximately 6 Kb Linkage-Disequilibrium
      [LD]-block) was associated with BPAD in case-control (p = .03) and family-based
      analyses (transmitted/nontransmitted [T/NT]-44/20; p = .003). Association was
      observed for rs2235349 and rs2076137 with SCZ and ss16339163 with BPAD in case
      control study. Using Block 2 haplotype tagging single nucleotide polymorphisms
      (htSNPs), GC haplotype revealed association (p = .02) and excess transmission (p
      = .002) with BPAD. CONCLUSIONS: Association of MLC1 with SCZ and BPAD suggests
      involvement of a common pathway. Rare missense mutations and common variants
      associated with BPAD favors hypothesis about likely involvement of both rare and
      common polymorphisms in etiology of this complex disorder.

PMID- 15992520
TI  - Cortical thinning in cingulate and occipital cortices in first episode
      schizophrenia.
AB  - BACKGROUND: Postmortem studies examining discrete regions show reduced cortical
      thickness in schizophrenia. Computational image analysis methods allow spatially
      detailed cortical thickness measurements across the entire cortex in 3D, but have
      not addressed thickness changes in cingulate or other cortices bordering the
      medial walls of the cerebral hemispheres in first episode schizophrenia. METHODS:
      Magnetic resonance images and cortical pattern matching methods were used to
      compare gray matter thickness, measured at sub-voxel resolution at thousands of
      spatially equivalent locations on the medial hemispheric surfaces, between 72
      (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls
      similar in age. Group differences were mapped in 3D, and their overall
      significance was confirmed by permutation testing. RESULTS: Patients with little
      or no prior antipsychotic medication treatment showed significant cortical
      thinning within cingulate, occipital and frontopolar cortices with no significant
      increases in any cortical location. Regional sex differences were observed with
      pronounced thinning in the left paracentral lobule and right posterior cingulate
      in male and female patients respectively compared to same sex controls.
      CONCLUSIONS: Cortical thinning may correspond to cytoarchitectural and
      neurochemical abnormalities observed in similar anatomic locations and may
      underlie systems-wise disturbances that include heteromodal association cortices,
      where cortical thinning has been previously observed in first episode
      schizophrenia.

PMID- 15992521
TI  - Impact of schizophrenia and chronic antipsychotic treatment on [123I]CNS-1261
      binding to N-methyl-D-aspartate receptors in vivo.
AB  - BACKGROUND: Antipsychotic drugs modulate N-methyl-D-aspartate (NMDA) receptor
      function in animals. The novel single photon emission tomography (SPET)
      radiotracer [123I]CNS-1261 binds to the PCP/MK-801 intrachannel site of the NMDA
      receptor, allowing the noninvasive estimation of NMDA receptor activity in living
      humans. We used [123I]CNS-1261 to determine whether binding to the NMDA receptor
      intrachannel PCP/MK-801 site is affected by schizophrenia or by treatment with
      typical antipsychotics and clozapine in vivo. METHODS: Three groups of
      schizophrenia patients were recruited-drug free (n = 5), typical antipsychotic
      treated (n = 7), and clozapine treated (n = 9)-as well as a control group of
      healthy normal volunteers (n = 13). All underwent [123I]CNS-1261 SPET scanning.
      Total volume of distribution of [123I]CNS-1261 was determined within predefined
      user-independent regions of interest after alignment of all images to a common
      template. RESULTS: There was no apparent difference in total volume of
      distribution of [123I]CNS-1261 in drug-free patients relative to healthy control
      subjects. A nonsignificant reduction in total volume of distribution was observed
      in typical antipsychotic treated patients. A significant decline in total volume
      of distribution of [123I]CNS-1261 was observed in all examined brain regions in
      the clozapine-treated patient group relative to healthy control subjects (p <
      .005). CONCLUSIONS: Clozapine treatment resulted in a global reduction in
      [123I]CNS-1261 binding to the NMDA receptor intrachannel PCP/MK-801 site in vivo.
      This supports an effect of the drug on glutamatergic systems that could be
      exploited for future antipsychotic drug discovery.

PMID- 15992522
TI  - The influence of encoding strategy on episodic memory and cortical activity in
      schizophrenia.
AB  - BACKGROUND: Recent work suggests that episodic memory deficits in schizophrenia
      may be related to disturbances of encoding or retrieval. Schizophrenia patients
      appear to benefit from instruction in episodic memory strategies. We tested the
      hypothesis that providing effective encoding strategies to schizophrenia patients
      enhances encoding-related brain activity and recognition performance. METHODS:
      Seventeen schizophrenia patients and 26 healthy comparison subjects underwent
      functional magnetic resonance imaging scans while performing incidental encoding
      tasks of words and faces. Subjects were required to make either deep
      (abstract/concrete) or shallow (alphabetization) judgments for words and deep
      (gender) judgments for faces, followed by subsequent recognition tests. RESULTS:
      Schizophrenia and comparison subjects recognized significantly more words encoded
      deeply than shallowly, activated regions in inferior frontal cortex (Brodmann
      area 45/47) typically associated with deep and successful encoding of words, and
      showed greater left frontal activation for the processing of words compared with
      faces. However, during deep encoding and material-specific processing (words vs.
      faces), participants with schizophrenia activated regions not activated by
      control subjects, including several in prefrontal cortex. CONCLUSIONS: Our
      findings suggest that a deficit in use of effective strategies influences
      episodic memory performance in schizophrenia and that abnormalities in functional
      brain activation persist even when such strategies are applied.

PMID- 15992523
TI  - Sensory contributions to impaired prosodic processing in schizophrenia.
AB  - BACKGROUND: Deficits in affect recognition are prominent features of
      schizophrenia. Within the auditory domain, patients show difficulty in
      interpreting vocal emotional cues based on intonation (prosody). The relationship
      of these symptoms to deficits in basic sensory processing has not been previously
      evaluated. METHODS: Forty-three patients and 34 healthy comparison subjects were
      tested on two affective prosody measures: voice emotion identification and voice
      emotion discrimination. Basic auditory sensory processing was measured using a
      tone-matching paradigm and the Distorted Tunes Test (DTT). A subset of subjects
      was also tested on facial affect identification and discrimination tasks.
      RESULTS: Patients showed significantly impaired performance on all emotion
      processing tasks. Within the patient group, a principal components analysis
      demonstrated significant intercorrelations between basic pitch perception and
      affective prosodic performance. In contrast, facial affect recognition deficits
      represented a distinct second component. Prosodic affect measures correlated
      significantly with severity of negative symptoms and impaired global outcome.
      CONCLUSIONS: These results demonstrate significant relationships between basic
      auditory processing deficits and impaired receptive prosody in schizophrenia. The
      separate loading of auditory and visual affective recognition measures suggests
      that within-modality factors may be more significant than cross-modality factors
      in the etiology of affect recognition deficits in schizophrenia.

PMID- 15992524
TI  - Cerebral cortical gray expansion associated with two second-generation
      antipsychotics.
AB  - BACKGROUND: Second-generation antipsychotics (SGAs) differ from first-generation
      antipsychotics (FGAs) with respect to induction of less extrapyramidal morbidity,
      partially reducing negative symptoms, and causing modest improvement in
      neurocognitive functioning in patients with schizophrenia. SGAs demonstrate 5
      HT2a antagonism. Differential effects of SGAs and FGAs on cortical gray volumes
      are explored herein. METHODS: Cerebral cortical gray was examined volumetrically
      in 19 patients with schizophrenia before and following 28 days of treatment with
      two SGAs (risperidone and ziprasidone; n = 13) or a FGA (haloperidol; n = 6).
      Seven (untreated) control subjects were also assessed at a similar interval.
      RESULTS: During treatment with the SGAs risperidone and ziprasidone, cerebral
      cortical gray of 13 patients with schizophrenia expanded 20.6 +/- 11.4 cc (p <
      .0005). Six patients receiving the FGA haloperidol, as well as 7 control
      subjects, showed no change in cortical gray volumes (p = .983 and p = .932,
      respectively) at the time of reassessment. CONCLUSIONS: Volumetric increase of
      cerebral cortical gray occurred early in the course of treatment with the SGAs
      ziprasidone and risperidone, but not with the FGA haloperidol. Such cortical gray
      expansion may be relevant to the reported enhanced neurocognition and quality of
      life associated with SGA treatment.

PMID- 15992525
TI  - Partial reversal of phencyclidine-induced impairment of prepulse inhibition by
      secretin.
AB  - BACKGROUND: Secretin is a "gut-brain" peptide whose neural function is as yet
      poorly understood. Several clinical studies have reported modestly increased
      social interaction in autistic children following intravenous secretin
      administration. Very recently secretin also was administered to schizophrenic
      patients and found to increase social interaction in some individuals. METHODS:
      In light of this finding, we assessed the ability of secretin to reverse
      phencyclidine- (PCP) induced impairment in prepulse inhibition (PPI), a leading
      animal model of sensorimotor gating deficits in schizophrenia. RESULTS: Similar
      to atypical antipsychotics, secretin (1, 3, 10, 30, and 100 microg/kg) partially
      and dose-dependently reversed the PCP-induced deficit in PPI without
      significantly affecting baseline startle when administered intraperitoneally (IP)
      10 minutes following IP administration of PCP (3 mg/kg). CONCLUSIONS: This
      finding may be relevant to observations of antipsychotic efficacy of secretin in
      schizophrenic patients as well as our previous report that systemically
      administered secretin is capable of modulating conditioned fear, even at quite
      low doses.

PMID- 15992526
TI  - Positive association of the oxytocin receptor gene (OXTR) with autism in the
      Chinese Han population.
AB  - BACKGROUND: Previous research has suggested that the social impairments exhibited
      by individuals with autism are associated with changes in plasma oxytocin (OT)
      levels. The physiologic effects of oxytocin are mediated through its specific
      receptors (OTRs), and numerous studies have implicated OTRs in the regulation of
      social cognition and behavior. Animal models and linkage data from genome screens
      indicate that the oxytocin receptor gene (OXTR) is an excellent candidate for
      research concerning psychiatric disorders, particularly those involving social
      impairments, such as autism. METHODS: We genotyped four single nucleotide
      polymorphisms (SNPs) located within the OXTR gene of 195 Chinese Han autism
      trios, using polymerase chain reaction-restriction fragment length polymorphism
      analysis. RESULTS: The family-based association test (FBAT) revealed a
      significant genetic association between autism and two of the SNPs tested
      (rs2254298 A: Z = 2.287, p = .0222; rs53576 A: Z = 2.573, p = .0101). When
      haplotypes were constructed with two, three, and four markers, the haplotype
      specific FBAT revealed that a number of haplotypes, particularly those involving
      rs53576, were significantly associated with autism. Furthermore, haplotypes
      constructed with all markers showed a significant excess transmission for the
      specific and global haplotype analyses (p = .0020 and .0289, respectively).
      CONCLUSIONS: These data suggest an involvement of OXTR in the susceptibility to
      autism, and replication is important.

PMID- 15992527
TI  - No association between the putative functional ZDHHC8 single nucleotide
      polymorphism rs175174 and schizophrenia in large European samples.
AB  - BACKGROUND: It has been recently reported that a functional variant in the ZDHHC8
      gene encoding a putative palmitoyltransferase directly confers susceptibility to
      schizophrenia in females (). METHODS: We investigated the putative risk allele
      (rs175174) in four schizophrenia association samples including a Bulgarian
      proband and parent sample (474 trios) and three case-control panels of European
      origin (1028 patients/1253 control subjects) in an attempt to replicate these
      findings. RESULTS: Our results do not support the hypothesis that genetic
      variation at rs175174 is associated with increased risk for schizophrenia nor do
      they suggest the presence of gender-specific differences. CONCLUSIONS: Our data
      suggest that the reported genetic association by either represents type I error
      resulting from sampling variance or that rs175174 is in linkage disequilibrium
      (LD) with the functional variant for schizophrenia and different LD patterns
      obscure the detection of association.

PMID- 15992528
TI  - Foetal surgery and cleft lip and palate: current status and new perspectives.
AB  - Now-a-days, high-resolution ultrasound allows an accurate and relatively early
      diagnosis of congenital malformations. In a limited number of such conditions
      foetal surgery may be lifesaving. However, premature labour has been the major
      drawback for open foetal surgery. Recently, improvement of video-endoscopic
      technology has boosted the development of operative techniques for feto
      endoscopic surgery, which has been demonstrated to be less invasive than the open
      approach. Main clinical application of fetoscopic procedures today is the
      treatment of feto-foetal transfusion syndrome. Although still in development,
      feto-endoscopic surgery seems to offer new hope for surgical foetal therapy not
      only in cases of life threatening conditions. Experimental intrauterine
      correction of cleft lip and palate (CLP) has been lately performed using the feto
      endoscopic approach. This procedure offers two major advantages: first, scarless
      foetal wound healing and bone healing without callus formation, which would also
      allow a better/normal maxillary growth, and second, significant decrease of
      foetal and maternal morbidity. Herein, we report the current status of
      experimental and clinical foetal surgery and propose possible directions for
      continuing research to make intrauterine procedures safer. Furthermore, we
      discuss current knowledge and new perspectives of experimental foetal cleft lip
      and palate repair, which in the future may lead to such excellent results in the
      operative treatment of clefts, that less or no secondary corrections and
      therapies, such as orthodontic, dental, logopedic, etc. would be needed. Only if
      these conditions can be fulfilled, will we be able to improve substantially our
      therapy for the human foetus with a cleft lip and palate. In spite of all
      efforts, however, it must be considered that it may not ever be possible to find
      the optimal treatment method for this or other craniofacial malformations.

PMID- 15992529
TI  - A simple new technique for neo-umbilicoplasty.
AB  - This article describes a new technique for reconstruction of the umbilicus. The
      technique used simply originated from a few clinical cases in which we were
      confronted with an absent or destroyed umbilicus. Previously described techniques
      for neo-umbilicoplasty were unsatisfying or seemed too complex in our hands. We
      introduce this easy, safe and reproducible technique which in our experience
      resulted in a very acceptable newly formed umbilicus.

PMID- 15992530
TI  - Necrotising fasciitis: clinical features in patients with liver cirrhosis.
AB  - Necrotising fasciitis is a fulminant and life-threatening infection. It is
      associated with a high mortality rate and is often seen in the aged and
      immunocompromised patients. Liver cirrhosis is regarded as a risk factor of
      necrotising fasciitis. From January 1995 to December 2003, 17 cirrhotic patients
      who had been admitted to our hospital for necrotising fasciitis were identified.
      The infection all developed in the lower extremities. Only six patients survived,
      and the overall case fatality rate was 64.7%. The cases were divided into two
      groups: survivors and nonsurvivors. Comparisons were made on age, gender,
      presenting symptoms, underlying medical diseases, laboratory data and clinical
      course. Underlying diabetes mellitus and grade C liver cirrhosis were the only
      statistically significant factors that led to poor prognosis (p< 0.05).

PMID- 15992531
TI  - Activated protein C resistance due to factor V Leiden, elevated coagulation
      factor VIII and postoperative deep vein thrombosis in late breast reconstruction
      with a free TRAM flap: a report of two cases.
AB  - Thromboembolic complications can endanger free flap surgery and cause
      postoperative morbidity and even mortality. The underlying cause of thrombosis is
      multifactorial; major surgery may trigger hereditary thrombophilic disorders
      leading to overt thrombotic events. This paper reports two cases with
      postoperative deep vein thrombosis after late breast reconstruction with a TRAM
      flap. Both showed APC resistance due to factor V Leiden and elevated coagulation
      factor VIII. One of the patients also had an event of both arterial and venous
      anastomotic thrombosis postoperatively.

PMID- 15992532
TI  - Hemangioma of the lower lip associated with schistosomiasis: a case report.
AB  - Hemangiomas may occur in any region of the body, and is the most common tumour of
      the childhood age. The first case report of multiple Schistosoma mansoni larvae
      associated with hemangioma of the lower lip is presented. A 7-year-old boy
      presented with hemangioma of the lower lip. The tumour was subtotally excised
      under general anaesthesia for aesthetic reasons. The histopathologic diagnosis
      was multiple Schistosoma mansoni larvae associated with the hemangioma. Patient
      was treated with an antischistosomal drug.

PMID- 15992533
TI  - Fresh cadaver dissection for training in plastic surgery.

PMID- 15992534
TI  - Badly drawn bra.

PMID- 15992535
TI  - Failure to identify the sentinel lymph node for cutaneous melanoma--significant
      prognostic and management implications.

PMID- 15992537
TI  - Bacteria-host-cell interactions at the plasma membrane: stories on actin
      cytoskeleton subversion.
AB  - Exploitation of the host-cell actin cytoskeleton is pivotal for many microbial
      pathogens to enter cells, to disseminate within and between infected tissues, to
      prevent their uptake by phagocytic cells, or to promote intimate attachment to
      the cell surface. To accomplish this, these pathogens have evolved common as well
      as unique strategies to modulate actin dynamics at the plasma membrane, which
      will be discussed here, exemplified by a number of well-studied bacterial
      pathogens.

PMID- 15992538
TI  - Signaling to cytoskeletal dynamics during chemotaxis.
AB  - We review insights in signaling pathways controlling cell polarization and
      cytoskeletal organization during chemotactic movement in Dictyostelium amoebae
      and neutrophils. We compare and contrast these insights with our current
      understanding of pathways controlling chemotactic movements in more-complex
      multicellular developmental contexts.

PMID- 15992539
TI  - TIPs are tension-responsive proteins involved in myogenic versus adipogenic
      differentiation.
AB  - Stretch induces lung embryonic mesenchymal cells to follow a myogenic pathway.
      Using this system we identified a set of stretch-responsive factors, which we
      referred to as TIPs (tension-induced/inhibited proteins). TIPs displayed
      signature motifs characteristic of nuclear receptor coregulators and chromatin
      remodeling enzymes. A genomic BLAST search suggested that the three TIPs
      identified were isoforms originated by alternative splicing from a single gene.
      Functional studies revealed that TIP-1 and TIP-3 were involved in the cell's
      selection of the myogenic or the adipogenic pathway. TIP-1, induced by stretch,
      promoted myogenesis, while TIP-3, inhibited by stretch, stimulated adipogenesis.
      The selection involved TIP-mediated chromatin remodeling via a histone
      acetylation process and depended on TIP-1 and TIP-3 nuclear receptor binding
      boxes (NRBs). This study, therefore, suggests a new developmental mechanism
      linking the presence or absence of tension with divergent differentiation
      pathways.

PMID- 15992540
TI  - gurken and the I factor retrotransposon RNAs share common localization signals
      and machinery.
AB  - Drosophila gurken mRNA is localized by dynein-mediated transport to a crescent
      near the oocyte nucleus, thus targeting the TGFalpha signal and forming the
      primary embryonic axes. Here, we show that gurken and the I factor, a non-LTR
      retrotransposon, share a small consensus RNA stem loop of defined secondary
      structure, which forms a conserved signal for dynein-mediated RNA transport to
      the oocyte nucleus. Furthermore, gurken and the I factor compete in vivo for the
      same localization machinery. I factor transposition leads to its mRNA
      accumulating near and within the oocyte nucleus, thus causing perturbations in
      gurken and bicoid mRNA localization and axis specification. These observations
      further our understanding of the close association of transposable elements with
      their host and provide an explanation for how I factor transposition causes
      female sterility. We propose that the transposition of other elements may exploit
      the host's RNA transport signals and machinery.

PMID- 15992541
TI  - The fission yeast homolog of the human transcription factor EAP30 blocks meiotic
      spindle pole body amplification.
AB  - Centrosome aberrations caused by misregulated centrosome maturation result in
      defective spindle and genomic instability. Here we report that the fission yeast
      homolog of the human transcription factor EAP30, Dot2, negatively regulates
      meiotic spindle pole body (SPB, the yeast equivalent of centrosome) maturation.
      dot2 mutants show excess electron-dense material accumulating near SPBs, which we
      refer to as aberrant microtubule organization centers (AMtOCs). These AMtOCs
      assemble multipolar spindles, leading to chromosome missegregation. SPB
      aberrations were associated with elevated levels of Pcp1, the fission yeast
      ortholog of pericentrin/kentrin, and reducing pcp1(+) expression significantly
      suppressed AMtOCs in dot2-439 cells. Our findings, therefore, uncover meiosis
      specific regulation of SPB maturation and provide evidence that a member of the
      conserved EAP30 family is required for maintenance of genome stability through
      regulation of SPB maturation. EAP30 is part of a transcription factor complex
      associated with acute myeloid leukemia, so these results may have relevance to
      human cancer.

PMID- 15992542
TI  - The dynein light chain Tctex-1 has a dynein-independent role in actin remodeling
      during neurite outgrowth.
AB  - Coordinated microtubule and microfilament changes are essential for the
      morphological development of neurons; however, little is know about the
      underlying molecular machinery linking these two cytoskeletal systems. Similarly,
      the indispensable role of RhoGTPase family proteins has been demonstrated, but it
      is unknown how their activities are specifically regulated in different neurites.
      In this paper, we show that the cytoplasmic dynein light chain Tctex-1 plays a
      key role in multiple steps of hippocampal neuron development, including initial
      neurite sprouting, axon specification, and later dendritic elaboration. The
      neuritogenic effects elicited by Tctex-1 are independent from its cargo adaptor
      role for dynein motor transport. Finally, our data suggest that the selective
      high level of Tctex-1 at the growth cone of growing axons drives fast neurite
      extension by modulating actin dynamics and also Rac1 activity.

PMID- 15992543
TI  - In vivo dynamics of clathrin and its adaptor-dependent recruitment to the actin
      based endocytic machinery in yeast.
AB  - Clathrin-mediated transport is a major pathway for endocytosis. However, in
      yeast, where cortical actin patches are essential for endocytosis, plasma
      membrane-associated clathrin has never been observed. Using live cell imaging, we
      demonstrate cortical clathrin in association with the actin-based endocytic
      machinery in yeast. Fluorescently tagged clathrin is found in highly mobile
      internal trans-Golgi/endosomal structures and in smaller cortical patches. Total
      internal reflection fluorescence microscopy showed that cortical patches are
      likely endocytic sites, as clathrin is recruited prior to a burst of intensity of
      the actin patch/endocytic marker, Abp1. Clathrin also accumulates at the cortex
      with internalizing alpha factor receptor, Ste2p. Cortical clathrin localizes with
      epsins Ent1/2p and AP180s, and its recruitment to the surface is dependent upon
      these adaptors. In contrast, Sla2p, End3p, Pan1p, and a dynamic actin
      cytoskeleton are not required for clathrin assembly or exchange but are required
      for the mobility, maturation, and/or turnover of clathrin-containing endocytic
      structures.

PMID- 15992544
TI  - Sortilin is essential and sufficient for the formation of Glut4 storage vesicles
      in 3T3-L1 adipocytes.
AB  - Impaired translocation of the glucose transporter isoform 4 (Glut4) to the plasma
      membrane in fat and skeletal muscle cells may represent a primary defect in the
      development of type 2 diabetes mellitus. Glut4 is localized in specialized
      storage vesicles (GSVs), the biological nature and biogenesis of which are not
      known. Here, we report that GSVs are formed in differentiating 3T3-L1 adipocytes
      upon induction of sortilin on day 2 of differentiation. Forced expression of
      Glut4 prior to induction of sortilin leads to rapid degradation of the
      transporter, whereas overexpression of sortilin increases formation of GSVs and
      stimulates insulin-regulated glucose uptake. Knockdown of sortilin decreases both
      formation of GSVs and insulin-regulated glucose uptake. Finally, we have
      reconstituted functional GSVs in undifferentiated cells by double transfection of
      Glut4 and sortilin. Thus, sortilin is not only essential, but also sufficient for
      biogenesis of GSVs and acquisition of insulin responsiveness in adipose cells.

PMID- 15992545
TI  - Plant development is regulated by a family of auxin receptor F box proteins.
AB  - The plant hormone auxin has been implicated in virtually every aspect of plant
      growth and development. Auxin acts by promoting the degradation of
      transcriptional regulators called Aux/IAA proteins. Aux/IAA degradation requires
      TIR1, an F box protein that has been shown to function as an auxin receptor.
      However, loss of TIR1 has a modest effect on auxin response and plant
      development. Here we show that three additional F box proteins, called AFB1, 2,
      and 3, also regulate auxin response. Like TIR1, these proteins interact with the
      Aux/IAA proteins in an auxin-dependent manner. Plants that are deficient in all
      four proteins are auxin insensitive and exhibit a severe embryonic phenotype
      similar to the mp/arf5 and bdl/iaa12 mutants. Correspondingly, all TIR1/AFB
      proteins interact with BDL, and BDL is stabilized in triple mutant plants. Our
      results indicate that TIR1 and the AFB proteins collectively mediate auxin
      responses throughout plant development.

PMID- 15992546
TI  - Beta-catenin and Hedgehog signal strength can specify number and location of hair
      follicles in adult epidermis without recruitment of bulge stem cells.
AB  - Using K14deltaNbeta-cateninER transgenic mice, we show that short-term, low-level
      beta-catenin activation stimulates de novo hair follicle formation from sebaceous
      glands and interfollicular epidermis, while only sustained, high-level activation
      induces new follicles from preexisting follicles. The Hedgehog pathway is
      upregulated by beta-catenin activation, and inhibition of Hedgehog signaling
      converts the low beta-catenin phenotype to wild-type epidermis and the high
      phenotype to low. beta-catenin-induced follicles contain clonogenic keratinocytes
      that express bulge markers; the follicles induce dermal papillae and provide a
      niche for melanocytes, and they undergo 4OHT-dependent cycles of growth and
      regression. New follicles induced in interfollicular epidermis are derived from
      that cellular compartment and not through bulge stem cell migration or division.
      These results demonstrate the remarkable capacity of adult epidermis to be
      reprogrammed by titrating beta-catenin and Hedgehog signal strength and establish
      that cells from interfollicular epidermis can acquire certain characteristics of
      bulge stem cells.

PMID- 15992547
TI  - Inositol polyphosphates regulate zebrafish left-right asymmetry.
AB  - Vertebrate body plans have a conserved left-right (LR) asymmetry manifested in
      the position and anatomy of the heart, visceral organs, and brain. Recent studies
      have suggested that LR asymmetry is established by asymmetric Ca2+ signaling
      resulting from cilia-driven flow of extracellular fluid across the node. We
      report here that inositol 1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1), which
      generates inositol hexakisphosphate, is critical for normal LR axis determination
      in zebrafish. Zebrafish embryos express ipk1 symmetrically during gastrulation
      and early segmentation. ipk1 knockdown by antisense morpholino oligonucleotide
      injection randomized LR-specific gene expression and organ placement, effects
      that were associated with reduced intracellular Ca2+ flux in cells surrounding
      the ciliated Kupffer's vesicle, a structure analogous to the mouse node. Our data
      suggest that the pathway for inositol hexakisphosphate production is a key
      regulator of asymmetric Ca(2+) flux during LR specification.

PMID- 15992548
TI  - Left-right asymmetry in the sea urchin embryo is regulated by nodal signaling on
      the right side.
AB  - The asymmetric positioning of internal organs on the left or right side of the
      body is highly conserved in vertebrates and relies on a Nodal signaling pathway
      acting on the left side of the embryo. Whether the same pathway also regulates
      left-right asymmetry in invertebrates and what is the evolutionary origin of the
      mechanisms controlling left-right determination are not known. Here, we show that
      nodal regulates left-right asymmetry in the sea urchin but that, intriguingly,
      its expression is reversed compared to vertebrates. Nodal signals emitted from
      the right side of the larva prevent the right coelomic pouch from forming the
      imaginal rudiment. Inhibition of Nodal signaling after gastrulation causes
      formation of an ectopic rudiment on the right side, leading to twinned urchins
      after metamorphosis. In contrast, ectopic activation of the pathway prevents
      formation of the rudiment. Our results show that the mechanisms responsible for
      left-right determination are conserved within basal deuterostomes.

PMID- 15992549
TI  - Tsix silences Xist through modification of chromatin structure.
AB  - X inactivation is controlled by Xist and its antisense gene, Tsix, neither of
      which encodes a protein. Xist is essential for X inactivation to occur in cis,
      and its differential expression is a key event in the initiation of X
      inactivation. Xist and Tsix are imprinted in the extraembryonic tissues of mouse
      embryos so that they are expressed from the paternal and maternal X,
      respectively, resulting in the preferential inactivation of the paternal X.
      Targeted disruption of Tsix causes ectopic expression of Xist, suggesting that
      Tsix negatively regulates Xist in cis. However, the molecular mechanism of this
      antisense regulation remains unknown. Here, we demonstrate that Tsix
      transcriptionally silences Xist in both embryonic and extraembryonic tissues of
      mouse embryos. Moreover, we show that disruption of Tsix impairs establishment of
      repressive epigenetic modifications and chromatin structure at the Xist locus. We
      propose that Tsix silences Xist through modification of the chromatin structure.

PMID- 15992550
TI  - Epidural versus spinal anesthesia for cesarean section in preeclamptic patients.

PMID- 15992551
TI  - Infertility in northern Tanzania.

PMID- 15992552
TI  - Second-trimester pregnancy termination with oral misoprostol in women who have
      had one cesarean section.

PMID- 15992553
TI  - Corticosteroid status influences the volume of the rat cingulate cortex - a
      magnetic resonance imaging study.
AB  - Imbalances in the corticosteroid milieu result in reductions in hippocampal
      volume in humans and experimental rodents. The functional correlates of these
      changes include deficits in cognitive performance and regulation of the
      hypothalamic-pituitary-adrenal axis. Since other limbic structures which are
      intricately connected with the hippocampal formation, also play an important role
      in behavioural and neuroendocrine functions, we here used magnetic resonance
      imaging (MRI) to analyse how two of these areas, the anterior cingulate and
      retrosplenial cortex, respond to chronic alterations of adrenocortical status:
      hypocortisolism (induced by adrenalectomy, ADX), normocortisolism (ADX with low
      dose corticosterone replacement), and hypercortisolism (ADX with high-dose
      dexamethasone supplementation). Hypercortisolism was associated with a
      significant reduction in the volume (absolute and normalized) of the left
      anterior cingulate gyrus as measured by MRI and confirmed using classical
      histological methods; a similar trend was observed in the right anterior
      cingulate region. In contrast, hypercortisolism did not influence the volume of
      the adjacent retrosplenial cortex. The volumes of the anterior cingulate gyrus
      and retrosplenial cortex were unaffected by the absence of adrenocortical
      hormones. These findings are the first to suggest that corticosteroid influences
      on the structure of the limbic system extend beyond the hippocampal formation,
      i.e., to fronto-limbic areas also.

PMID- 15992554
TI  - Changes in prefrontal activity characterize clinical response in SSRI
      nonresponders: a pilot study.
AB  - Previous studies in unipolar depression have shown that early decreases in
      prefrontal values of the QEEG cordance measure identified responders to
      pharmacotherapy. These studies have all examined individuals who were drug-free
      prior to the first physiologic assessment, yet in the clinical management of
      treatment resistant depression (TRD), many patients undergo changes in treatment
      without a drug-free interval between treatments. Here, we investigated whether
      cordance decreases were associated with response in Stage I TRD subjects without
      wash-out between treatment trials. Awake EEGs were recorded from 12 adults with
      unipolar depression. Subjects were receiving naturalistic treatment, had failed
      SSRI monotherapy, and were starting a new treatment prescribed by their treating
      psychiatrists. EEG data were recorded before starting the new treatment and after
      approximately 1 week. Six of the 12 subjects responded to treatment after 8--10
      weeks. Five of the six responders showed an early cordance decreases, compared
      with two of the six nonresponders (accurate characterization in 75% of the
      cases). Consistent with previous treatment trials, decreases in prefrontal
      cordance differentiated responders from nonresponders in this setting as well.
      These findings suggest that cordance biomarkers may be a useful tool in
      effectiveness trials that parallel clinical practices in SSRI nonresponders, and
      may not require a wash-out period between treatments.

PMID- 15992555
TI  - Simultaneous use of thyrotropin-releasing hormone test and combined
      dexamethasone/corticotropine-releasing hormone test for severity evaluation and
      outcome prediction in patients with major depressive disorder.
AB  - We performed a prospective study designed to examine whether or not evaluation of
      the severity and prediction of treatment outcome in major depressive disorder
      would be enabled by simultaneous use of the thyrotropin-releasing hormone (TRH)
      test and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH)
      test. We studied consecutive patients hospitalized for major depressive disorder.
      The patients received the TRH test and the DEX/CRH test on the 4th through the
      7th hospital days and at the time of improvement. None of the indices in these
      tests at the time of admission correlated with the Hamilton rating scale for
      depression (HRSD) or the Global Assessment for Function (GAF). However, since the
      DeltaMAXACTH, ACTHAUC, DeltaMAXcortisol, and CortisolAUC showed significant
      decreases at the time of improvement compared with the time of admission,
      suggesting that the DEX/CRH test can be a state marker. DeltaMAXTSH showed no
      significant change. Prediction of improvement within 3 months after admission was
      not possible with either test alone. However, the quotient which divided
      DeltaMAXACTH by DeltaMAXTSH was predictive of clinical improvement with a
      sensitivity of 50% and a specificity of 100%. The simultaneous use of the TRH
      test and the DEX/CRH test seems to provide a more useful biological marker than
      the separate use of either test alone in patients with major depressive disorder.

PMID- 15992556
TI  - Lack of association between single nucleotide polymorphisms in the corticotropin
      releasing hormone receptor 1 (CRHR1) gene and alcohol dependence.
AB  - While the physiological mechanisms that contribute to the development of alcohol
      dependence remain unclear, a number of recent studies have indicated a role for
      the corticotropin releasing hormone receptor 1 (CRHR 1) in modulating the
      response of the central nervous system to ethanol. Based on these data, the
      present study aims to identify associations between variations in the CRHR 1 gene
      and alcohol dependence in a population of individuals of European ancestry. In
      order to identify such putative associations, five single nucleotide
      polymorphisms (SNPs) in the CRHR 1 gene were analyzed in 120 alcohol dependent
      and 180 control subjects. In comparing both allele and genotype frequencies at
      these five loci between alcohol dependent and control populations, no significant
      associations between variations in the CRHR 1 gene and alcohol dependence were
      detected. The results of this study suggest that polymorphisms in the CRHR 1 gene
      are not major risk factors for the development of alcohol dependence in persons
      of European ancestry.

PMID- 15992557
TI  - Assessing insomnia severity in depression: comparison of depression rating scales
      and sleep diaries.
AB  - Depression and sleep researchers typically assess insomnia severity differently.
      Whereas depression researchers usually assess insomnia with items on depression
      symptom inventories, sleep researchers usually assess the subjective experience
      of insomnia with sleep diaries. The present manuscript utilizes baseline data
      from 397 participants in a large multi-site chronic depression study to assess
      agreement between these two methodologies. The results indicate that the early,
      middle, and late insomnia items of the Hamilton Rating Scale for Depression
      (HRSD(24)) and the Inventory of Depression Symptoms - Self Report (IDS-SR(30))
      are highly correlated with the weekly mean values of time to sleep onset, time
      awake after sleep onset, and time awake prior to the planned wake-up obtained
      from prospective sleep diaries. Results also reveal significant correspondence
      between the weekly-mean of daily sleep efficiency, an accepted measure of sleep
      continuity (the ratio between reported time asleep and time in bed), and the
      insomnia scale scores of the HRSD(24) and the IDS-SR(30) (the mean score on the
      three insomnia items of each depression measure). Unit increments in HRSD(24)
      scores for early, middle and late insomnia were associated with significant
      increases in unwanted minutes awake for corresponding periods on sleep diaries.
      Similar relationships were found for early insomnia on the IDS-SR(30) but not for
      middle and late insomnia. Overall, with few exceptions, findings revealed
      substantial agreement between the HRSD(24), IDS-SR(30) and prospective sleep
      diary data. The study supports the validity of the sleep items and sleep
      subscales of the HRSD(24) and the IDS-SR(30) as global measures of insomnia
      severity in depression. Conventional sleep assessment procedures can complement
      depression scales by providing additional information about specific aspects of
      sleep in depression.

PMID- 15992558
TI  - Increased delta power and discrepancies in objective and subjective sleep
      measurements in borderline personality disorder.
AB  - BACKGROUND: Previous studies have shown depression-like sleep abnormalities in
      borderline personality disorder (BPD). However, findings in BPD are not
      unequivocal for REM dysregulation, as well as for a decrement of slow wave sleep
      and sleep continuity disturbances. Earlier findings in sleep EEG abnormalities in
      BPD may have been confounded by concomitant depressive symptoms. METHODS: Twenty
      unmedicated female BPD patients without current comorbid major depression and 20
      sex- and age-matched control subjects entered the study. Conventional
      polysomnographic parameters and for the first time sleep EEG spectral power
      analysis was performed on two sleep laboratory nights. Subjective sleep
      parameters were collected by sleep questionnaires in order to assess the
      relationship between objective and subjective sleep measurements. RESULTS: BPD
      patients showed a tendency for shortened REM latency and significantly decreased
      NonREM sleep (stage 2). Spectral EEG analysis showed increased delta power in
      total NREM sleep as well as in REM sleep in BPD patients. Subjective ratings
      documented drastically impaired sleep quality in BPD patients for the two weeks
      before the study and during the two laboratory nights. CONCLUSION: Not-depressed
      BPD patients only showed tendencies for depression-like REM sleep abnormalities.
      Surprisingly, BPD patients displayed higher levels of delta power in the sleep
      EEG in NREM sleep than healthy control subjects. There was a marked discrepancy
      between objective and subjective sleep measurements, which indicates an altered
      perception of sleep in BPD. The underlying psychological and neurobiological
      mechanisms of these alterations are still unclear and need to be clarified in
      future studies including interventions on a pharmacological and cognitive
      behavioral level.

PMID- 15992559
TI  - Poor premorbid social functioning and theory of mind deficit in schizophrenia:
      evidence of reduced context processing?
AB  - Investigations have demonstrated deficits in theory of mind (ToM) ability in
      schizophrenia. Yet, the development of, and mechanisms associated with these
      deficits are not well understood. The present investigation examined the
      hypothesis that, among chronic schizophrenia patients, impaired ToM is associated
      with failures in context processing, greater disorganized symptoms, and poor
      premorbid functioning. Forty-two inpatients with schizophrenia spectrum disorders
      were assessed on tests of ToM, visual and linguistic context processing,
      executive functioning, and verbal IQ. Symptomatology and premorbid functioning
      were also assessed. Results revealed that more impaired ToM was associated with
      poorer performance on both visual and linguistic context processing measures and
      higher ratings of disorganization on the BRRS. ToM was also associated with
      poorer childhood social functioning and an earlier age of illness onset. ToM was
      not associated with verbal processing speed, verbal fluency, response inhibition,
      sequence learning, or estimated verbal IQ. A significant regression model
      including measures of childhood peer problems and visual and language context
      processing significantly predicted ToM performance and accounted for 43% of the
      variance. These findings suggest that, among chronic schizophrenia patients,
      deficits in ToM ability may be the result of context processing impairments.
      These impairments may be a factor in both poor social functioning during
      childhood and greater disorganized symptoms after illness onset.

PMID- 15992560
TI  - Physiological responsivity to emotional pictures in schizophrenia.
AB  - Schizophrenic patients are known to experience difficulties in emotional
      information processing, yet knowledge of their physiological responsivity to
      emotional stimuli is limited. The purpose of this study was to investigate the
      physiological reactions of schizophrenic patients to emotional stimuli. We
      presented pictures selected from the International Affective Picture System
      (IAPS) to patients and controls, while assessing their subjective evaluations in
      terms of valence and arousal scores and measuring their responses of heart rate
      (HR), breathing rate (BR), skin conductance level (SCL) and diastolic (DBP) and
      systolic blood pressure (SBP). For the analysis of the physiological data, three
      emotional picture categories were formed: positive (erotic content), negative
      (physical injuries) and neutral (landscapes). Patients and controls did not
      differ in their subjective evaluations of the pictures. Also, for both patients
      and controls, the SCL and DBP responses to positive emotional pictures were
      larger as compared to negative and neutral pictures. However, the patients did
      show significantly increased HR responses to the positive emotional pictures as
      compared to controls, possibly as a result of a decreased parasympathetic
      activity. Only for the BR response to the positive emotional pictures did we
      observe significant positive correlations with the PANSS scores. These first data
      suggest that altered physiological responsivity to emotional pictures in
      schizophrenia is limited to those with positive emotional content. Further
      studies will need to refine the dynamics of this stimulus category in relation to
      clinical state and medication effects.

PMID- 15992561
TI  - Loss of efferent vagal activity in acute schizophrenia.
AB  - An increased heart rate has been reported in schizophrenia. It is unclear whether
      this is due to disease-related autonomic nervous system changes or a side effect
      of antipsychotic medication. Altered cardiac autonomic function might to some
      extent account for the elevated cardiovascular mortality rate of schizophrenic
      patients. We assessed heart rate variability (HRV) in 30 acute unmedicated
      schizophrenic patients and matched controls. Patients were re-investigated 2--4
      days after initiation of treatment to assess effects of medication. Our study
      demonstrates that non-medicated schizophrenic patients were significantly
      different in heart rate (increase) and parasympathetic parameters (loss of
      efferent vagal activity) at rest and during deep respiration. No significant
      effect was found after initiation of neuroleptic therapy. We found a correlation
      between duration of disease and parasympathetic parameters as well as very low
      frequency power (VLF) and delusion (SAPS subscale). These data suggest that
      schizophrenia is accompanied by a loss of vagal efferent activity, probably due
      to disturbed cortical-subcortical circuits modulating the autonomic nervous
      system in acute psychosis. The definite mechanisms by which vagal activity might
      be suppressed in schizophrenia are unknown. Parasympathetic hypoactivity might
      increase the risk for sudden cardiac death and arrhythmias in this disease.
      Future studies are warranted to investigate the interaction between cardiac
      autonomic function and schizophrenia and to identify patients on risk.

PMID- 15992562
TI  - What accounts for vertigo one year after neuritis vestibularis - anxiety or a
      dysfunctional vestibular organ?
AB  - One year after neuritis vestibularis, 29% from a sample of 75 patients still
      complained of vertigo. The objective of this investigation was to study why
      patients suffer from persisting vertigo. The alternative hypotheses were that the
      vertigo experienced could be explained either by a persisting vestibular
      dysfunction or by psychopathological changes. To elucidate this question,
      patients were examined with dynamic posturography, the symptom check list (SCL 90
      R), the state-trait anxiety inventory (STAI), the agoraphobic cognitions
      questionnaire (ALQ) and the body sensations questionnaire (BSQ). After one year,
      only two patients had overall pathological results in the posturography.
      Following the assumption that sub-clinical dysfunction of the organs of balance
      can also lead to an altered body perception in combination with anxiety, the
      pathological results of posturographic sub-tests were related to experiences of
      vertigo. Here also there were no significant associations. However, vertigo
      correlated highly significantly with body-related anxiety and anxiety-related
      apprehension. In conclusion, chronic vertigo after an acute vestibular disorder
      could be regarded as a somatopsychic process. Persisting experience of vertigo is
      not explained by sub-clinical organic changes. Anxiety seems to be the crucial
      factor in persisting vertigo.

PMID- 15992563
TI  - Decline of immune responsiveness: a pathogenetic factor in Alzheimer's disease?
AB  - The involvement of immunological alterations in the pathogenesis of Alzheimer's
      disease (AD) is widely discussed. Hitherto, findings on systemic immunological
      alterations are inconsistent. We measured the concentrations of the pro
      inflammatory cytokines IL-1beta, IL-2, IL-6, and TNF-alpha, and of the soluble
      receptors sIL-2r, sIL-6r, and sTNF-alphar, in cerebrospinal fluid (CSF) and serum
      of 20 Alzheimer patients and 21 controls. Moreover, we studied levels of the pro
      inflammatory IL-6, Il-12, IFN-gamma, and TNF-alpha, and of the anti-inflammatory
      IL-5 and IL-13 in stimulated blood cell cultures from 27 AD patients and 25
      controls. The levels in CSF and serum were diminished in AD or under detection
      limit. In mitogen-stimulated blood cultures we found a significant decrease of
      pro- and anti-inflammatory cytokines in the AD group. Our data suggest a general
      decline of immune responsiveness in AD. Based on the recent research, an impaired
      immune response may be considered as a pathogenetically relevant factor in AD.
      With respect to the putative role of ageing in AD, we assume a premature
      immunosenescence contributing to the Alzheimer's pathology.

PMID- 15992564
TI  - Increasing leptin precedes craving and relapse during pharmacological abstinence
      maintenance treatment of alcoholism.
AB  - The appetite regulating peptide leptin has recently been associated with craving
      for alcohol and lifetime ethanol intake. However, effects of anti-craving drugs
      on leptin have not been studied until now. The objective of our study was to test
      the hypothesis whether leptin plasma concentration in abstinent alcohol addicts
      during treatment with naltrexone vs. acamprosate is associated with abstinence
      duration and craving for alcohol. Leptin plasma concentration was measured in 160
      recently detoxified alcohol addicts during a double-blind, placebo-controlled
      relapse prevention trial with naltrexone vs. acamprosate vs. naltrexone plus
      acamprosate. During placebo treatment, increasing leptin plasma concentration was
      observed, whereas during combined treatment with naltrexone and acamprosate,
      leptin decreased significantly. The change from baseline of leptin plasma levels
      after weeks 4, 8 and 12 was inversely correlated with duration of abstinence and,
      after 4 weeks, positively correlated with self-rated craving. In summary, the
      study presents first evidence for an association of increasing leptin plasma
      concentrations with relapse to renewed alcohol intake in detoxified alcoholics.
      Moreover, there are hints for an interaction between pharmacological anti-craving
      treatment, plasma concentration of leptin, and abstinence duration.

PMID- 15992565
TI  - Bioterrorism, stress, and pain: the importance of an anticipatory community
      preparedness intervention.
AB  - This article reviews the accumulating scientific evidence demonstrating the
      negative impact caused by a cataclysmic event, such as bioterrorism, on the
      mental health of a community. Moreover, the potential mental health problems
      created by the continuing threat of possible future events are discussed. This
      close link among disaster events, stress, pain, and psychopathology is presented
      from a biopsychosocial perspective. Although there are now efforts being
      systematically developed to prepare for possible future biological or chemical
      terrorism events, there is currently also a critical need for early mental health
      intervention in response to future attacks to decrease psychiatric sequelae,
      especially workforce illness and morbidity. In this article, examples of such
      emergency bioterrorism preparedness, incorporating a major focus on mental health
      issues, are reviewed. Although these are now recognized needs, there is still not
      a concerted effort to prepare the population for the mental health sequelae that
      would be produced by such events.

PMID- 15992567
TI  - Understanding why women delay in seeking help for breast cancer symptoms.
AB  - OBJECTIVE: The aim of this study was to improve our understanding of why women
      delay their presentation with breast cancer. METHODS: A review of the evidence
      for the adverse effect of delayed presentation on survival and the risk factors
      for delay was conducted. The description and rationale for a model to explain the
      delay process are presented. RESULTS: Delays of 3 months or more adversely affect
      survival. Older age, the nature of the breast symptom, not disclosing the symptom
      to someone close, negative attitudes towards general practitioner (GP) and fears
      about cancer treatment are risk factors for delay. Using elements of self
      regulation theory, the theory of planned behaviour (TPB) and implementation
      intentions, a theoretical model is proposed to explain delayed help-seeking. The
      model incorporates stages of symptom appraisal, attitudes towards help-seeking
      and translating intentions into behaviour. CONCLUSIONS: Placing the empirical
      risk factors for delayed presentation in a theoretically derived model should
      enable the development of an effective intervention to reduce delay and thereby
      save lives.

PMID- 15992566
TI  - Pain and deliberate self-harm: an important association.
AB  - OBJECTIVE: The aim of this study was to establish how often pain was a factor
      contributing to an episode of deliberate self-harm. METHOD: Retrospective case
      note examination of all deliberate self-harm patients with concurrent medical
      problems admitted to a general hospital over 2 years. RESULTS: Pain was
      considered to be a contributory factor in the episode of deliberate self-harm in
      75 (4%) of the total number of episodes of deliberate self-harm (1665) over the 2
      year period. These patients were older and had higher suicide intent scores, but
      lower rates of previous psychiatric illness or alcohol or drug misuse than did
      the deliberate self-harm patients with medical problems but no pain. Although 60%
      had experienced pain for more than 6 months only, 8 (12%) were attending the
      local Pain Clinic at the time of the deliberate self-harm. CONCLUSION: We propose
      closer collaboration between general hospital services and local pain clinics for
      deliberate self-harm patients with painful disorders. Clinicians need to assess
      suicidal ideation and risk of self-harm when prescribing for this population.

PMID- 15992568
TI  - Assessing illness representations of breast cancer: a comparison of patients with
      healthy and benign controls.
AB  - OBJECTIVE: Illness representations of cancer may comprise inaccurate information,
      misconceptions, or negative conceptualizations of the disease, which may
      influence screening behaviors. This study examined the differences between
      healthy women's and breast cancer patients' representations of breast cancer.
      METHODS: The cross-sectional design involved 147 consecutive women free from
      breast diseases, or with benign breast conditions, and 102 patients with breast
      cancer recruited from the outpatient breast clinic of a public cancer hospital.
      Respondents completed a modified version of the Illness Perception Questionnaire
      (IPQ) that assessed six dimensions of illness representations of breast cancer.
      RESULTS: Multiple comparison tests revealed that nonmalignant women's illness
      representations were characterized by weak beliefs concerning breast cancer
      curability/controllability, combined with an overestimation of the negative
      physical, social, and economic consequences of breast cancer. Moreover, these
      women held stronger beliefs about the role of environmental factors (radiation
      exposure, diet, and pollution) in breast cancer causation and expressed greater
      disagreement on the role of chance in the onset and course of the illness.
      CONCLUSION: Illness representations of breast cancer appear to play a significant
      role in determining the unfavorable and exaggerated way in which laywomen
      perceive breast cancer. This is discussed within the framework of the social
      construction of the disease, which portrays breast cancer as a fatal and
      disfiguring disease, and the strong influence lay literature and the media exert
      on it.

PMID- 15992569
TI  - A 1-year prospective study of individual variation in distress, and illness
      perceptions, after treatment for breast cancer.
AB  - OBJECTIVE: The primary objective was to conduct a detailed analysis of individual
      variation in psychological morbidity in the year following surgery for breast
      cancer. The salience of the patients' "illness perceptions" to morbidity was
      examined as a secondary objective. METHODS: Psychological morbidity was assessed
      with the General Health Questionnaire (GHQ-28) in a prospective study of 371
      women having surgery for primary breast cancer. Patients also completed the
      Illness Perception Questionnaire (IPQ), Mental Adjustment to Cancer Scale (MAC)
      and the Eysenck Personality Scales (EPS). Assessments were made postoperatively
      and at 3, 6 and 12 months after surgery. RESULTS: Whilst descriptive statistics
      indicated a general reduction in mean distress over the 12-month follow-up, close
      analysis showed that a quarter of all patients maintained clinically significant
      levels of distress throughout the period. Patients with chronically elevated
      distress were characterised by higher levels of neuroticism, greater symptom
      awareness, more pain and poorer self-rated general health. In the regression
      analysis, psychological morbidity across the 1-year follow-up was predicted
      principally by the immediate postoperative state of distress, IPQ symptom
      awareness and the perceived time line of the illness, general health and, to a
      more minor extent, by neuroticism. CONCLUSION: There is marked individual
      variation in psychological morbidity in the year following breast cancer surgery,
      which is reliably predicted by the patient's immediate postoperative state of
      distress, her perception of the impact of the symptoms and the time line of the
      disease. Subgroups of patients with chronically high distress are characterised
      by factors including personality and negative perceptions and beliefs about their
      illness.

PMID- 15992570
TI  - Moods in everyday situations: effects of menstrual cycle, work, and stress
      hormones.
AB  - OBJECTIVE: This study examined women's mood responsiveness on work and off days
      during different phases of the menstrual cycle. METHODS: Self-reports of
      negative, positive, and energy dimensions of mood were obtained throughout the
      day on two work and two off days during the luteal and follicular phases of the
      menstrual cycle in 203 women nurses. Individual differences in daytime and
      nighttime epinephrine, norepinephrine, and cortisol were assessed. RESULTS: High
      daytime norepinephrine, epinephrine, and cortisol levels were associated with
      higher ratings of stress and tired, and with lower ratings of happy. The phase of
      the menstrual cycle and the day factor (workday, off day) were also associated
      with mood differences, and the direction of the effects depended on hormone
      levels and hormone sampling period. CONCLUSION: The experience of moods is
      affected by the arousal-related interaction of hormone levels with the phase of
      the menstrual cycle and occupational stress.

PMID- 15992571
TI  - Breast feeding, bottle feeding, and maternal autonomic responses to stress.
AB  - OBJECTIVE: The aim of this study was to examine the effects of breast feeding on
      autonomic nervous system (ANS) response to stressors. METHODS: Sympathetic and
      parasympathetic activities were examined before, during, and after standard
      laboratory stressors in women who were either exclusively breast feeding (n=14)
      or nonexclusively breast feeding (n=14), and in non-postpartum controls (n=15).
      RESULTS: Mothers who breast fed exclusively showed greater levels of
      parasympathetic cardiac modulation and slower heart rate (HR) throughout the
      session and less HR increase and preejection period (PEP) shortening to mental
      arithmetic (MA) than did nonexclusive breast feeders and controls. Nonexclusive
      breast-feeders showed greater electrodermal reactivity to, and greater
      differences in skin conductance response (SCR) frequency between baseline and
      recovery from cold pressor (CP) than did either exclusive breast-feeders or
      controls. Sympathetic activity was negatively related to the number of breast
      feedings and positively related to bottle feedings. CONCLUSION: Breast feeding
      shifts maternal ANS balance toward relatively greater parasympathetic and lesser
      sympathetic activity; the opposite occurs with bottle feeding. The frequency of
      feeding also is a critical factor in determining breast feeding effects on
      maternal ANS function.

PMID- 15992572
TI  - Is the chronic fatigue syndrome an exercise phobia? A case control study.
AB  - OBJECTIVE: The aim of this study was to test whether patients with chronic
      fatigue syndrome (CFS) have an exercise phobia, by measuring anxiety-related
      physiological and psychological reactions to ordinary activity and exercise.
      METHODS: Patients and healthy but sedentary controls were assessed over 8 h of an
      ordinary day, and before, during and after an incremental exercise test on a
      motorised treadmill. To avoid confounding effects, those with a comorbid
      psychiatric disorder were excluded. Heart rate, galvanic skin resistance (GSR)
      and the amount of activity undertaken were measured, along with state and trait
      measures of anxiety. RESULTS: Patients with CFS were more fatigued and sleep
      disturbed than were the controls and noted greater effort during the exercise
      test. No statistically significant differences were found in either heart rate or
      GSR both during a normal day and before, during and after the exercise test.
      Patients with CFS were more symptomatically anxious at all times, but this did
      not increase with exercise. CONCLUSION: The data suggest that CFS patients
      without a comorbid psychiatric disorder do not have an exercise phobia.

PMID- 15992573
TI  - A longitudinal study of physical activity and body mass index among persons with
      unexplained chronic fatigue.
AB  - OBJECTIVE AND METHODS: A cohort of 100 patients with unexplained chronic fatigue
      (CF) was assessed longitudinally for 1.5 years to determine if physical activity
      (kcal expended), exercise capacity (VO(2)max), perceived exertion, and body mass
      index (BMI) changed over time and were associated with changes in CF-related
      clinical status. RESULTS: BMI increased significantly over time but did not
      predict changes in clinical status. Increasing energy expenditure was associated
      with increasing vitality and decreasing CF symptom severity over time, and
      decreasing perceived exertion was associated with increasing physical
      functioning. However, increasing perceived exertion was also associated with
      increasing CF symptoms. CONCLUSIONS: These data do not support models that posit
      associations between CF and deconditioning.

PMID- 15992574
TI  - The effects of repeated thermal therapy for two patients with chronic fatigue
      syndrome.
AB  - OBJECTIVE: This paper describes the successful treatment of two patients with
      chronic fatigue syndrome (CFS) using repeated thermal therapy. METHODS: Two
      patients with CFS underwent treatment with prednisolone (PSL), with no
      satisfactory effect. They were subjected to thermal therapy that consisted of a
      far-infrared ray dry sauna at 60 degrees C and postsauna warming. The therapy was
      performed once a day, for a total of 35 sessions. After discharge, these subjects
      continued the therapy once or twice a week on an outpatient basis for 1 year.
      RESULTS: Symptoms such as fatigue, pain, sleep disturbance, and low-grade fever
      were dramatically improved after 15 to 25 sessions of thermal therapy. Although
      PSL administration was discontinued, the subjects showed no relapse or
      exacerbation of symptoms during the first year after discharge. The patients
      became socially rehabilitated 6 months after discharge. CONCLUSIONS: These
      results suggest that repeated thermal therapy might be a promising method for the
      treatment of CFS.

PMID- 15992575
TI  - Premorbid "overactive" lifestyle and stress-related pain/fatigue syndromes.

PMID- 15992576
TI  - Differential binding properties of [3H]dextrorphan and [3H]MK-801 in
      heterologously expressed NMDA receptors.
AB  - The N-methyl-D-aspartate receptor (NMDAR) antagonists: MK-801, phencyclidine and
      ketamine are open-channel blockers with limited clinical value due to
      psychotomimetic effects. Similarly, the psychotomimetic effects of the
      dextrorotatory opioids, dextromethorphan and its metabolite dextrorphan, derive
      from their NMDAR antagonist actions. Differences in the use dependency of
      blockade, however, suggest that the binding sites for MK-801 and dextrorphan are
      distinct. In the absence of exogenous glutamate and glycine, the rate of
      association of [3H]MK-801 with wild-type NR1-1a/NR2A receptors was considerably
      slower than that for [3H]dextrorphan. Glutamate individually, and in the presence
      of the co-agonist glycine, had substantial effects on the specific binding of
      [3H]MK-801, while the binding of [3H]dextrorphan was not affected. Mutation of
      residues N616 and A627 in the NR1 subunit had a profound effect on [3H]MK-801
      binding affinity, while that of [3H]dextrorphan was unaltered. In contrast, NR1
      residues, W611 and N812, were critical for specific binding of [3H]dextrorphan to
      NR1-1a/NR2A complexes with no corresponding influence on that of [3H]MK-801.
      Thus, [3H]dextrorphan and [3H]MK-801 have distinct molecular determinants for
      high-affinity binding. The ability of [3H]dextrorphan to bind to a closed
      channel, moreover, indicates that its recognition site is shallower in the ion
      channel domain than that of MK-801 and may be associated with the extracellular
      vestibule of the NMDAR.

PMID- 15992577
TI  - Adenosine receptors co-operate with NMDA preconditioning to protect cerebellar
      granule cells against glutamate neurotoxicity.
AB  - N-Methyl-D-aspartate (NMDA) preconditioning is evoked by subtoxic concentrations
      of NMDA (50 microM), which has been shown previously to lead to transient
      resistance to subsequent lethal dose of glutamate or NMDA in cultured neurons.
      The purpose of this study was to investigate the participation of adenosine A1
      and A2A receptors on NMDA preconditioning against glutamate-induced cellular
      damage in cerebellar granule cells. NMDA preconditioning prevented the
      stimulatory effect induced by glutamate on AMP hydrolysis, but not on ADP
      hydrolysis. The neuroprotection evoked by NMDA preconditioning against glutamate
      induced cellular damage was prevented by the presence of adenosine A1 receptor
      antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT, 100 nM), but not by the
      adenosine A2A receptors antagonist, (4-(2[7-amino-2-(2-furyl {1,2,4}-triazolo{2,3
      a{1,3,5}triazian-5-yl-aminoethyl)phenol (ZM 241385, 50 nM). Interestingly, a long
      term treatment with CPT or ZM 241385 alone protected cells against glutamate
      induced neurotoxicity. Moreover, the functionality of adenosine A1 receptor was
      not affected by NMDA preconditioning, but this treatment promoted adenosine A2A
      receptor desensitization, measured by cAMP accumulation. Taken together, the
      results described herein suggest that the neuroprotection evoked by NMDA
      preconditioning against cellular damage elicited by glutamate occurs through
      mechanisms involving adenosine A2A receptors desensitization co-operating with
      adenosine A1 receptors activation in cerebellar granule cells.

PMID- 15992578
TI  - A role for the anandamide membrane transporter in TRPV1-mediated neurosecretion
      from trigeminal sensory neurons.
AB  - Many n-acylethanolamines utilize the anandamide membrane transporter (AMT) to
      gain facilitated access to the intracellular compartment, hence, we hypothesized
      that this mechanism might be important for anandamide (AEA)- and N-arachidonoyl
      dopamine (NADA)-evoked CGRP release from cultured trigeminal ganglion (TG)
      neurons. Using [14C]AEA we demonstrated that TG neurons transported AEA in a FAAH
      and AMT-inhibitable fashion. Although TRPV1-positive TG neurons were found to
      express fatty acid amide hydrolase, the application of FAAH inhibitors had no
      effect on AEA-evoked CGRP release. In contrast, application of the AMT inhibitors
      OMDM-2 or VDM-11 significantly reduced the potency and efficacy of AEA-, NADA-
      and capsaicin-evoked CGRP release. Moreover OMDM-2 (IC50 values ranging from 6.4
      9.6 microM) and VDM-11 (IC50 values ranging from 5.3-11 microM) inhibited CGRP
      release evoked by EC80 concentrations of AEA, NADA and CAP and these values were
      consistent with IC50s obtained for inhibition of uptake. OMDM-2 had no effect on
      CGRP release per se while VDM-11 evoked CGRP release on its own (EC50
      approximately 35 microM) in a CPZ-insensitive, but ruthenium red (RR)-sensitive
      fashion. This is the first demonstration that TG sensory neurons possess an AMT
      like mechanism suggesting that this mechanism is important for the
      pharmacological action of AEA and NADA at native TRPV1 channels.

PMID- 15992579
TI  - Serotonin 5-HT7 receptors coupled to induction of interleukin-6 in human
      microglial MC-3 cells.
AB  - Brain serotonin 5-HT(7) receptors are known to be expressed in neurons and
      astrocytes. We now report the presence of these receptors in a third type of
      cell, microglial cells. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5
      CT), 5-methoxytryptamine (5-MeOT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8
      OH-DPAT) induced concentration-dependent stimulations of cAMP accumulation in the
      human microglial MC-3 cell line. The maximal effect of 5-HT was 3.4+/-0.3-fold
      stimulation (mean+/-S.E.M., n=5) above basal levels. The rank order of agonist
      potency (pEC50 values) was 5-CT (7.09)>5-HT (6.13)>or=5-MeOT (5.78)>>8-OH-DPAT
      (ca. 5). The effect of 5-CT was inhibited in a concentration-dependent manner by
      the selective 5-HT7 receptor antagonist SB-269970 (pA2 value 9.03). Western blot
      analysis revealed the presence of immunoreactive bands corresponding to the human
      5-HT7 receptor in extracts of MC-3 cells. The presence of two splice variants of
      the 5-HT7 receptor (5-HT7(a/b)) was visualized by reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis with specific primers. In real-time
      PCR studies, the mRNA for interleukin-6 (IL-6) was found to be increased by 2.5
      fold in MC-3 cells after 1 h incubation with 5-CT (1 microM) and this effect was
      fully blocked by the 5-HT7 receptor antagonist SB-269970 (1 microM). These data
      show that functional 5-HT7 receptors are present in human microglial MC-3 cells,
      suggesting that they are involved in neuroinflammatory processes.

PMID- 15992580
TI  - Endogenous gamma-aminobutyric acid (GABA)(A) receptor active neurosteroids and
      the sedative/hypnotic action of gamma-hydroxybutyric acid (GHB): a study in GHB-S
      (sensitive) and GHB-R (resistant) rat lines.
AB  - In the rat brain, gamma-hydroxybutyric-acid (GHB) increases the concentrations of
      3alpha-hydroxy,5alpha-pregnan-20-one (allopregnanolone, 3alpha,5alpha-THP) and
      3alpha,21-dihydroxy,5alpha-pregnan-20-one
      (allotetrahydrodeoxycorticosterone/3alpha,5alphaTHDOC), two neurosteroids acting
      as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors.
      This study was aimed at assessing whether neurosteroids play a role in GHB
      induced loss of righting reflex (LORR). Basal and GHB-stimulated brain
      concentrations of endogenous 3alpha,5alpha-THP and 3alpha,5alpha-THDOC were
      analyzed in two rat lines, GHB-sensitive (GHB-S) and GHB-resistant (GHB-R),
      selectively bred for opposite sensitivity to GHB-induced sedation/hypnosis. Basal
      neurosteroid concentrations were similar in brain cortex of the two rat lines.
      However, in male GHB-S rats, administration of GHB (1000 mg/kg, i.p., 30 min)
      increased brain cortical concentrations of 3alpha,5alpha-THP and 3alpha,5alpha
      THDOC 7- and 2.5-fold, respectively, whilst male GHB-R animals displayed only a 4
      and 2-fold increase, respectively. In GHB-S rats this increase lasted up to 90
      min and declined 180 min following GHB administration, a time course that matches
      LORR onset and duration. In contrast, in GHB-R rats, which failed to show GHB
      induced LORR, brain cortical 3alpha,5alpha-THP and 3alpha,5alpha-THDOC had
      returned to control values within 90 min. At onset of LORR, a similar increase in
      brain cortical levels of 3alpha,5alpha-THP and 3alpha,5alpha-THDOC (2-3-fold) was
      observed in GHB-S female rats and in the few female GHB-R rats that lost the
      righting reflex after GHB administration, but not in female GHB-R rats failing to
      show LORR. Sub-hypnotic doses (7.5 and 12.5 mg/kg, i.p.) of pregnanolone,
      administered 10 min before GHB, dose-dependently facilitated the expression of
      GHB-induced LORR in GHB-R male rats. These results suggest that the GHB-induced
      increases of brain 3alpha,5alpha-THP and 3alpha,5alpha-THDOC concentrations are
      implicated in the eliciting of the sedative/hypnotic action of GHB.

PMID- 15992581
TI  - Presynaptic alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate
      [3H]d-aspartate release from rat frontal cortex in vitro.
AB  - The presynaptic nicotinic modulation of glutamatergic transmission in the CNS has
      been associated with activation of the alpha7 subtype of nicotinic acetylcholine
      receptor (nAChR) in sub-cortical regions, whereas in the frontal cortex, non
      alpha7 nAChRs have been implicated. The aim of this investigation was to directly
      characterise nAChR-evoked release of excitatory amino acids from rat frontal
      cortex, by monitoring the release of [3H]D-aspartate from superfused synaptosomes
      or minces. Co-administration of a nAChR agonist with a depolarising stimulus
      enhanced [3H]D-aspartate release above the effect of depolarising agent alone.
      This enhancement was blocked by the nicotinic antagonist mecamylamine. Other
      experiments revealed that in the absence of a depolarising stimulus, the nAChR
      agonists nicotine, epibatidine and anatoxin-a could evoke the release of [3H]D
      aspartate in a Ca2+- and concentration-dependant manner. Differential sensitivity
      to the alpha7- and beta2*-selective nAChR antagonists alpha-bungarotoxin (alpha
      Bgt) and dihydro-beta-erythroidine (DHbetaE) implicated two nAChR subtypes
      (alpha7 and beta2*), and this was supported by using the subtype-selective
      agonists choline (10 mM; alpha7 selective, blocked by alpha-Bgt but not by
      DHbetaE) and 5-Iodo-A-85380 (10 nM; beta2*-selective, blocked by DHbetaE but not
      by alpha-Bgt). Immunocytochemistry showed that alpha-Bgt labelling was associated
      with structures immunopositive for vesicular glutamate transporters, in both
      frontal cortex sections and synaptosome preparations, supporting the presence of
      alpha7 nAChR on glutamatergic terminals in rat frontal cortex.

PMID- 15992582
TI  - mGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and
      deficit of prepulse inhibition.
AB  - Hypoglutamatergic theory of schizophrenia is substantiated by observation that
      high affinity uncompetitive antagonists of NMDA receptors such as PCP can induce
      psychotic symptoms in humans. Recently, metabotropic glutamate receptors of the
      mGluR5 type have also been discussed as possible players in this disease.
      However, less is known about the potential contribution of mGluR1 in
      schizophrenia. Therefore, the aim of the present study was to compare the effect
      of selective mGluR1 antagonist EMQMCM, (3-ethyl-2-methyl-quinolin-6-yl)-(4
      methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist (MTEP ([(2
      methyl-1, 3-thiazol-4-yl) ethynyl] pyridine) either alone or in combination with
      (+)MK-801 in a prepulse inhibition (PPI) model and locomotor activity tests.
      Additionally, the effect of both mGluR1 and mGluR5 antagonists on (+)MK-801
      evoked ataxia was tested. In contrast to (+)MK-801, which induced disruption of
      PPI, neither MTEP (1.25-5 mg/kg) nor EMQMCM (0.5-4 mg/kg) altered the PPI.
      However, MTEP, but not EMQMCM, enhanced disruption of PPI induced by (+)MK-801.
      Although neither mGluR1 nor mGluR5 antagonists given alone changed locomotor
      activity of rats, MTEP at 5 mg/kg potentiated the effect of (+)MK-801 while
      EMQMCM (up to 4 mg/kg) turned out to be ineffective. On the other hand, EMQMCM,
      but not MTEP, enhanced ataxia evoked by MK-801. The present results demonstrate
      that blockade of mGluR1 and mGluR5 evokes different effects on behavior induced
      by NMDA receptor antagonists.

PMID- 15992583
TI  - Identification, design, synthesis, and pharmacological activity of (4-ethyl
      piperazin-1-yl)-phenylmethanone derivatives with neuroprotective properties
      against beta-amyloid-induced toxicity.
AB  - In search of novel therapeutic approaches for Alzheimer's disease (AD), we report
      herein the identification, design, synthesis, and pharmacological activity of (4
      ethyl-piperaz-1-yl)-phenylmethanone derivatives with neuroprotective properties
      against beta-amyloid-induced toxicity. (4-ethyl-piperaz-1-yl)-phenylmethanone is
      a common substructure shared by molecules isolated from plants of the Asteraceae
      genus, traditionally used as restorative of lost or declining mental functions.
      (4-Ethyl-piperaz-1-yl)-phenylmethanone displayed strong neuroprotective
      properties against Abeta1-42 and reversed Abeta1-42-induced ATP depletion on
      neuronal cells, suggesting a mitochondrial site of action. Abeta1-42 has been
      described to induce a hyperactivity of the glutamate network in neuronal cells.
      (4-Ethyl-piperaz-1-yl)-phenylmethanone also inhibited the neurotoxic effect that
      glutamate displayed on PC12 cells, suggesting that the reduction of glutamate
      induced neurotoxicity may be one of the mechanisms by which this compound exerts
      its neuroprotective properties against the deleterious effects of the Abeta1-42.
      These data suggest that the identified (4-ethyl-piperaz-1-yl)-phenylmethanone
      chemical entity exerts neuroprotective properties and may serve as a lead
      compound for the development of novel therapies for AD.

PMID- 15992584
TI  - Effects of 17beta-estradiol on chemically induced long-term depression.
AB  - In this study, we have investigated the effects of 17beta-estradiol (E2) on
      chemically induced long-term depression (LTD). LTD was induced by a brief
      application of N-methyl-D-aspartate (NMDA) or (R,S)-3,5-dihydroxyphenylglycine
      (DHPG), a group I metabotropic glutamate receptor agonist. Bath application of E2
      alone potentiated population excitatory postsynaptic potentials. This
      potentiation was readily reversed by washing with control saline. The effect of
      E2 on NMDA-induced LTD was a conversion of LTD to long-term potentiation (LTP).
      An application of NMDA in the presence of E2 induced LTP. The induction of LTP
      was inhibited by an inhibitor of calcium/calmodulin dependent protein kinase
      (CaMKII). The results suggest that E2 potentiates NMDA receptor function and
      induces an increase in postsynaptic Ca2+ concentration. An increase in
      postsynaptic Ca2+ concentration activates CaMKII, leading to LTP. In contrast to
      NMDA-induced LTD, an application of DHPG in the presence of E2 induced
      significantly larger LTD. The results suggest that E2 potentiates an as yet
      unidentified process(es) in inducing LTD by an application of DHPG. The effects
      of E2 both on NMDA-induced and DHPG-induced LTD were suppressed by an estrogen
      receptor antagonist.

PMID- 15992585
TI  - Effects of emodin on synaptic transmission in rat hippocampal CA1 pyramidal
      neurons in vitro.
AB  - Rhubarb extracts provide neuroprotection after brain injury, but the mechanism of
      this protective effect is not known. The present study tests the hypothesis that
      rhubarb extracts interfere with the release of glutamate by brain neurons and,
      therefore, reduce glutamate excitotoxicity. To this end, the effects of emodin,
      an anthraquinone derivative extracted from Rheum tanguticum Maxim. Ex. Balf, on
      the synaptic transmission of CA1 pyramidal neurons in rat hippocampus were
      studied in vitro. The excitatory postsynaptic potential (EPSP) was depressed by
      bath-application of emodin (0.3-30 microM). Paired-pulse facilitation (PPF) of
      the EPSP was significantly increased by emodin. The monosynaptic inhibitory
      postsynaptic potential (IPSP) recorded in the presence of glutamate receptor
      antagonists (DNQX and AP5) was not altered by emodin. Emodin decreased the
      frequency, but not the amplitude, of the miniature EPSP (mEPSP). The inhibition
      of the EPSP induced by emodin was blocked by either 8-CPT, an adenosine A1
      receptor antagonist, or by adenosine deaminase. These results suggest that emodin
      inhibits the EPSP by decreasing the release of glutamate from Schaffer
      collateral/commissural terminals via the activation of adenosine A1 receptors in
      rat hippocampal CA1 area and that the neuroprotective effects of rhubarb extracts
      may result from decreased glutamate excitotoxicity.

PMID- 15992586
TI  - 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a
      selective dopamine D4 receptor antagonist.
AB  - 2-[4-(3,4-Dimethylphenlyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393) was
      identified as a potent dopamine D4 receptor antagonist with excellent receptor
      selectivity. [3H]-spiperone competition binding assays showed that A-381393
      potently bound to membrane from cells expressing recombinant human dopamine D4.4
      receptor (Ki=1.5 nM), which was 20-fold higher than that of clozapine (Ki=30.4
      nM). A-381393 exhibited highly selective binding for the dopamine D4.4 receptor
      (>2700-fold) when compared to D1, D2, D3 and D5 dopamine receptors. Furthermore,
      in comparison to clozapine and L-745870, A-381393 exhibits better receptor
      selectivity, showing no affinity up to 10 microM for a panel of more than 70
      receptors and channels, with the exception of moderate affinity for 5-HT2A
      (Ki=370 nM). A-381393 potently inhibited the functional activity of agonist
      induced GTP-gamma-S binding assay and 1 microM dopamine induced-Ca2+ flux in
      human dopamine D4.4 receptor expressing cells, but not in human dopamine D2L or
      D3 receptor cells. In contrast to L-745870, A-381393 did not exhibit any
      significant intrinsic activity in a D4.4 receptor. In vivo, A-381393 has good
      brain penetration after subcutaneous administration. A-381393 inhibited penile
      erection induced by the selective D4 agonist PD168077 in conscious rats. Thus, A
      381393 is a novel selective D4 antagonist that will enhance the ability to study
      dopamine D4 receptors both in vitro and in vivo.

PMID- 15992587
TI  - Abnormal synaptic plasticity in the Ts1Cje segmental trisomy 16 mouse model of
      Down syndrome.
AB  - Due to the homology between human chromosome 21 and mouse chromosome 16, trisomy
      16 mice are considered animal models of Down syndrome (DS). Abnormal hippocampal
      synaptic plasticity and behavior have been reported in the segmental trisomy 16
      Ts65Dn mouse. In the Ts1Cje DS mouse model, which has a shorter triplicated
      chromosomal segment than Ts65Dn, more subtle hippocampal behavioral deficits have
      been reported. In this study, we investigated CA1 hippocampal synaptic
      plasticity, long-term potentiation (LTP) and depression (LTD) in the Ts1Cje
      mouse. Field excitatory postsynaptic potentials (fEPSPs) were recorded from the
      CA1 area of in vitro hippocampal slices from the Ts1Cje mouse and diploid
      controls, LTP was induced by a single tetanizing train pulse (1 s) at 100 Hz and
      LTD by a 900-pulse train at 1 Hz. We report for the first time that compared to
      diploid controls, the hippocampus from the Ts1Cje mouse had a smaller LTP and an
      increased LTD. The changes are less dramatic than had been reported previously
      for the Ts65Dn mouse. Furthermore, in the Ts1Cje mouse trains of pulses at both
      20 Hz and 100 Hz produced a decrease in the evoked fEPSPs over the length of the
      train in comparison to diploid fEPSPs. These findings suggest that genes from
      Ts1Cje chromosome, including GIRK2 potassium channel, contribute to abnormal
      short- and long-term plasticity.

PMID- 15992588
TI  - Histamine excites noradrenergic neurons in locus coeruleus in rats.
AB  - Histamine is implicated in the control of many brain functions, in particular the
      control of arousal. Histaminergic neurons send dense projections through the
      entire brain, including the locus coeruleus (LC)--the main noradrenergic
      (NAergic) nucleus. In this study, we have examined the effect of bath-applied
      histamine on cells in the LC by single-unit recordings in slices and the
      expression of histamine receptors in this area by single-cell RT-PCR. Histamine
      (10 microM) increased the firing of NAergic cells to 130+/-9% of control, 100
      microM to 256+/-58% of control. This excitation was unaffected by blocking
      synaptic transmission. Histamine-mediated excitation was blocked by an H1
      receptor antagonist, mepyramine, in 78% of cells and by cimetidine, an H2
      receptor antagonist, in 42% of cells, but not by the H3 receptor antagonist,
      thioperamide. RT-PCR revealed that mRNA for the H1 receptor was expressed in 77%
      of isolated LC neurons, mRNA for the H2 receptor in 41% of LC neurons and H3
      receptors in 29%. These findings underline the coordination between aminergic
      systems and suggest that the arousal induced by the histamine system could
      involve excitation of noradrenergic neurons in the locus coeruleus.

PMID- 15992589
TI  - EROD induction and PCDD/F levels in fish liver from the Biobio River in Chile.
AB  - The Biobio River basin, located in central Chile, is one of the most important
      freshwater resources for a population of 1 million inhabitants. The river
      receives discharges of pulp mills, sewage treatment plants and there is a diffuse
      input of materials coming from the drainage basin. Previous studies reported high
      levels of etoxyresorufin-O-deethylase (EROD) induction in fish from the lower
      stretch of the river, mainly due to polycyclic aromatic hydrocarbons (PAHs) and
      polychlorinated biphenyls (PCBs) exposure. The present study investigates
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans
      (PCDFs) levels as well as EROD induction in fish livers from Central Chile's
      Biobio River. Dioxin and furan levels in fish livers are reported for the first
      time in three areas of the Basin. In all samples the highest concentrations were
      found for the octachlorodibenzo-p-dioxin (OCDD) and PCDD/F TEQ concentrations
      ranged from 2.83 to 6.33 ppt (wet weight). The results indicate a clear induction
      of EROD activity in different fish species as the river mouth is approached,
      although this induction is not clearly related with dioxin and furan levels found
      in the fish livers. Our results clearly show that other pollutants might be
      acting as EROD inductors in the Biobio Basin.

PMID- 15992590
TI  - Polybrominated diphenyl ethers and traditional organochlorine pollutants in
      fulmars (Fulmarus glacialis) from the Faroe Islands.
AB  - The observed high-level burdens of organohalogens among the residents of the
      Faroe Islands, needs to be explained. Long-finned pilot whale (Globicephala
      melas) blubber and meat are known sources of environmental exposure. The present
      study focus on the organohalogen contamination of the fulmar (Fulmarus
      glacialis). The compounds quantified in fulmar muscle, fat, and egg are PCBs,
      DDTs, hexachlorobenzene (HCB), and polybrominated diphenyl ethers (PBDEs). The
      dominating pollutants are the 4,4'-DDT metabolite 4,4'-DDE and the two PCB
      congeners, CB-153 and CB-180, which are present in geometric mean concentrations
      of 7100, 4700 and 2500 ng/g lipid weight (l.w.), respectively, in adult fulmar
      muscle. 4,4'-DDT and HCB concentrations are approximately 250 ng/gl.w., each.
      Concentrations in the eggs are about 50% of the fulmar muscle levels, due to
      differences in lipid amounts, 4% in muscle and 10% in the eggs, the exposure
      contribution on a fresh weight basis is almost the same. As a result, both the
      egg and the adult fulmar muscle may lead to a significant exposure risk, if
      consumed by humans. BDE-153, the most abundant PBDE congener in fulmar muscle,
      with a geometric mean concentration of 6.5 ng/gl.w., is much lower than the
      individual PCB congeners and 4,4'-DDE concentrations. In the adult fulmar muscle,
      the relative PBDE congener pattern is different from that previously observed in
      biota, with BDE-153 and BDE-154 as the dominating congeners, rather than BDE-47.
      In contrast, BDE-47 is the most abundant congener in juvenile muscle and
      subcutaneous fat. The summation operatorPBDE concentrations are almost the same
      in egg, muscle (adult and juvenile) and subcutaneous fat (juvenile). For the
      polybrominated biphenyl (BB-153) the concentrations are considerably higher in
      the adult bird and egg than in the juvenile bird; this is also seen for the PCB
      and 4,4'-DDE concentrations. PCB concentrations found in fulmar egg and muscle
      are in the same range as seen in the pilot whale, i.e. 590-5700 ng/gl.w. for CB
      153. Hence humans are also exposed to PCBs at a reasonable degree via intake of
      fulmar and/or fulmar egg and not only via pilot whale blubber.

PMID- 15992591
TI  - Heavy metals, PCDD/F and PCB in sewage sludge samples from two wastewater
      treatment facilities in Rio de Janeiro State, Brazil.
AB  - Two sewage sludge samples collected from an urban as well as a rural area in
      Brazil and one sludge sample originating from the city of Balingen, Baden
      Wurttemberg, South Germany, were investigated in respect to contamination with
      heavy metals, PCDD/F and PCB. The results were compared to PCDD/F and indicator
      PCB mean values found in the region of Baden-Wurttemberg. The observed toxicity
      equivalents of PCDD/F found in the Brazilian samples, were below the upper limit
      specified by German legislation for final disposal or agricultural use in soils.
      Both the PCB and heavy metal values exceeded this limit. The PCDD/F
      congener/homologue profiles found in the Brazilian samples indicated that the
      urban sewage sludge shows a contamination where both chlorophenols and
      depositional sources appear to be contributing to the contamination pool. The
      enrichment of highly chlorinated PCDD/F groups in the sludge of semi-rural origin
      is probably due to transport phenomena effects. For the German sludge sample,
      depositional sources seem to be the main PCDD/F contamination pathway. Regarding
      PCB, both Brazilian samples show a homologue profile that indicates a
      contamination stemming from technical PCB formulations like Clophen A50 and
      Clophen A60 or equivalent.

PMID- 15992592
TI  - Polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in the general
      population in Finland.
AB  - We measured adipose tissue concentrations of polychlorinated dibenzo-p-dioxins,
      dibenzofurans (PCDD/Fs), and polychlorinated biphenyls (PCBs) in 420 general
      Finns living in southern Finland. The mean (median) concentrations of WHO(PCDD/F)
      TEQ and WHO(PCB)-TEQ were 29.0 (24.1) and 20.7 (16.7) pg g-1 fat, respectively.
      The concentrations clearly correlated with age. Expressing the concentrations as
      a function of subject's ages revealed that the exposure of Finns has declined
      over the last 30 years. A downward gradient was found in the concentrations from
      the Baltic Sea coast to inland areas in Finland, and this was assessed to be due
      to consumption of the Baltic Sea fish, especially Baltic herring. Linear
      regression models for natural logarithm WHO(PCDD/F)-TEQ, natural logarithm
      WHO(PCB)-TEQ, and natural logarithm WHO(total)-TEQ, explained 70%, 69%, and 72%
      of the variability, respectively. Age, lactation, place of residence, and fish
      consumption frequencies were significant predictors in the models.

PMID- 15992593
TI  - In-series columns adsorption performance of Kraft mill wastewater pollutants onto
      volcanic soil.
AB  - Two in-series columns systems with volcanic soil were tested for wastewater
      pollutants adsorption capacity. The first system was tested with acidified
      volcanic soil and the second with a reactivated volcanic soil. The reactivated
      soil was obtained by washing the previous spent acidified soil system with an
      acid solution. The systems parameters were obtained using the Bohardt and Adams
      model for fixed-beds. The acidified soil parameters indicated an adsorption
      capacity q of 28 and 139 mg/g of phenolic compounds and color, respectively (for
      each column), compared to 12 and 39 mg/g for the reactivated soil system. The
      adsorption rate constant k ranged between 1.5x10(-6) and 2.8x10(-6) l/min mg and
      no significant difference was observed for each analysed column system and
      pollutant. Furthermore, the molecular weight distribution analysis of input and
      output samples of one acidified soil column indicated that the fraction >30000 Da
      is the most adsorbed until the breakpoint. Moreover, the CODs and tannins and
      lignin removal efficiencies at the breakpoint reached values between 60% and 70%
      in each column and each system, indicating that lower biodegradable compounds
      were retained effectively. The results indicate that it is possible to compare
      the acidified volcanic soil adsorption capacity with natural zeolites, and a
      preliminary costs evaluation indicates that volcanic soil could be also
      competitive, even when comparing with activated carbon.

PMID- 15992594
TI  - Contents and sources of polycyclic aromatic hydrocarbons and organochlorine
      pesticides in vegetable soils of Guangzhou, China.
AB  - We investigated contents, distribution and possible sources of PAHs and
      organochlorine pesticides (Ops) in 43 surface and subsurface soils around the
      urban Guangzhou where variable kinds of vegetables are grown. The results
      indicate that the contents of PAHs (16 US EPA priority PAHs) range from 42 to
      3077 microg/kg and the pollution extent is classified as a moderate level in
      comparison with other investigations and soil quality standards. The ratios of
      methylphenanthrenes to phenanthrene(MP/P), anthracene to anthracene plus
      phenanthrene (An/178), benz[a]anthracene to benz[a]anthracene plus chrysene
      (BaA/228), indeno[1,2,3-cd]pyrene to indeno[1,2,3-cd]pyrene plus
      benzo[ghi]perylene (In/In+BP) suggest that the sources of PAHs in the soil
      samples are mixed with a dominant contribution from petroleum and combustion of
      fossil fuel. The correlation analysis shows that the PAHs contents are
      significantly related to total organic carbon contents (TOC) (R2=0.75) and black
      carbon contents (BC) (R2=0.62) in the soil samples.
      Dichlorodiphenyltrichloroethane and metabolites (DDTs) and hexachlorocyclohexanes
      and metabolites (HCHs) account largely for the contaminants of OPs. The
      concentrations of DDTs range from 3.58 to 831 microg/kg and the ratios for
      DDT/(DDD+DDE) are higher than 2 in some soil samples, suggesting that DDT
      contamination still exists and may be caused by its persistence in soils and/or
      impurity in the pesticide dicofol. The concentrations of HCHs are 0.19-42.3
      microg/kg.

PMID- 15992595
TI  - Organochlorine residues in odontocete species from the southeast coast of India.
AB  - Blubber from bottle-nose dolphins, spinner dolphins, humpback dolphin (Tursiops
      truncatus, Stenella longirostris and Sousa chinensis) were collected from the Bay
      of Bengal (southeast coast of India) and analyzed for the organochlorine
      pesticides hexachlorocyclohexane (HCHs), p,p'-dichlorodiphenyl trichloroethane
      (DDTs), and polychlorinated biphenyls (PCBs). All nine specimens analyzed
      contained considerable levels of all the three chemical classes where DDT was in
      the range of 3330-23330 ng/g; HCHs in the range of 95-765 ng/g; and PCBs in the
      range of 210-1220 ng/g (wet weight basis). The reasons for this and the
      variations in the isomer pattern of HCHs and DDT and its metabolites in marine
      mammal tissues are discussed.

PMID- 15992596
TI  - Handling of dioxin measurement data in the presence of non-detectable values:
      overview of available methods and their application in the Seveso chloracne
      study.
AB  - Exposure measurements of concentrations that are non-detectable or near the
      detection limit (DL) are common in environmental research. Proper statistical
      treatment of non-detects is critical to avoid bias and unnecessary loss of
      information. In the present work, we present an overview of possible statistical
      strategies for handling non-detectable values, including deletion, simple
      substitution, distributional methods, and distribution-based imputation. Simple
      substitution methods (e.g., substituting 0, DL/2, DL/ radical2, or DL for the non
      detects) are the most commonly applied, even though the EPA Guidance for Data
      Quality Assessment discouraged their use when the percentage of non-detects is
      >15%. Distribution-based multiple imputation methods, also known as robust or
      "fill-in" procedures, may produce dependable results even when 50-70% of the
      observations are non-detects and can be performed using commonly available
      statistical software. Any statistical analysis can be conducted on the imputed
      datasets. Results properly reflect the presence of non-detectable values and
      produce valid statistical inference. We describe the use of distribution-based
      multiple imputation in a recent investigation conducted on subjects from the
      Seveso population exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in which
      55.6% of plasma TCDD measurements were non-detects. We suggest that distribution
      based multiple imputation be the preferred method to analyze environmental data
      when substantial proportions of observations are non-detects.

PMID- 15992598
TI  - Persistent organic pollutant patterns in grey seals (Halichoerus grypus).
AB  - The aim of this paper is to examine the patterns of polychlorinated biphenyls
      (PCB) in the grey seals (Halichoerus grypus) from the Baltic, Northeast and
      Eastern England, and the St. Lawrence Estuary (Canada). In fact, the feeding
      habits of the ringed seal (Phoca hispida) include ingestion of major quantities
      of benthic crustaceans that might cause observed differences obtained in PCBs,
      whereas the grey seal feed mainly on fish. The profile (percent in mixture) of
      polychlorinated biphenyls (PCB) 101, 118, 138, 153, and 180, and the total of
      their concentrations in mg/kg lipid in grey seals from the Baltic, from Northeast
      and Eastern England, and from the St. Lawrence estuary (Canada), were examined by
      principal component analysis (PCA). When considering the possible effects of
      consuming seafood by the grey seal, it is necessary to characterize populations
      and individuals according to the amounts they consume, since populations in
      different parts of the world are likely to show big differences in their
      consumption of seafood. The patterns differ between juveniles and adult animals,
      but the gender of adults and geography do not appear to play a role.

PMID- 15992597
TI  - T cell-derived IL-5 production is a sensitive target of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - The immune system is one of the organs most vulnerable to the toxicity of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Among the various immunotoxic effects of
      TCDD, the thymus involution and suppression of IgM antibody production are well
      known sensitive reactions of the thymocytes and B cells affected by TCDD.
      Recently, we reported that TCDD greatly inhibits the production of type-2 helper
      T (Th2) cell-derived cytokines, especially IL-5, by the splenocytes in mice
      immunized with ovalbumin (OVA). In the present study, we investigated the dose
      dependency of these TCDD immunotoxic effects in OVA-immunized mice to identify
      the most sensitive target. Mice of two age groups, 6 weeks old and 3 weeks old,
      were dosed with 0.3, 1.0, or 3.0 microg TCDD/kg and immunized with OVA using alum
      as an adjuvant. Seven days later, the thymus weight, thymocyte population,
      antigen-specific IgM in the plasma, and IL-5 production by the splenocytes were
      examined. Among them, IL-5 production was significantly suppressed by all three
      doses of TCDD and reduced to about 30% by even a small dose of 0.3 microg TCDD/kg
      in both age groups. The thymus weight was significantly reduced by 1.0 microg or
      3.0 microg TCDD/kg, but IgM production was not affected by up to 3.0 microg/kg of
      TCDD in both age groups. Taken together, the Th2 cell-derived IL-5 production was
      the most sensitive endpoint detecting TCDD toxicity among those examined. Our
      results also suggest that effector T cells are targets more vulnerable to TCDD
      toxicity than thymocytes or antibody-producing B cells in the OVA-immunized mice.

PMID- 15992599
TI  - Photochemical studies of a polybrominated diphenyl ethers (PBDES) technical
      mixture by solid phase microextraction (SPME).
AB  - In this work the photochemical behaviour of a technical mixture of polybrominated
      diphenyl ethers (PBDEs) (BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154) has been
      studied. The mixture of BDEs was extracted from aqueous solutions using SPME
      fibers that were subsequently exposed to different UV irradiation times,
      procedure so-called Photo-SPME. PBDEs photochemical studies in such medium have
      been accomplished for the first time. Twenty one different photoproducts, all of
      them generated by successive bromine atoms losses, have been identified, being
      their photoformation-photodegradation curves easily determined by the Photo-SPME
      technique.

PMID- 15992600
TI  - Tissue distribution and bioconcentration factors of PCDD/Fs in the liver and
      adipose tissue following chronic ingestion of contaminated milk in rats.
AB  - The aim of this study was to determine the tissue distribution of 17 PCDD/Fs
      following the chronic ingestion of contaminated milk in rats and to assess the
      "target tissue/milk" BioConcentration Factors (BCFs) of these molecules.
      Contaminated milk, collected in a polluted area, has been incorporated into the
      diet of male rats at a low dose (31 pg I-TEQ/day/rat). For this exposure, the
      accumulation of PCDD/Fs in target tissues (liver and adipose tissue) was limited,
      the tissue concentrations stabilising between 90 and 120 days of daily intake to
      levels close to 3 pg/g of tissue (all tissues and molecules combined). The tissue
      distribution seemed to be governed by the congeners properties and by the tissue
      characteristics. An increase in the chlorination degree of dioxins caused a
      decrease in their incorporation in the adipose tissue, and consequently of the
      BCF values. Moreover, the distribution of dioxins between hepatocytes and
      adipocytes differed: unlike the liver, the quantities of dioxins in the adipose
      tissue were significantly (P<0.05) correlated to the quantity of tissue fat. Only
      in the liver, the incorporation of PCDDs seemed to be facilitated when the
      chlorination degree of these congeners increased, the reverse phenomenon having
      been observed for PCDFs. However, for the same level of chlorination, the BCFs of
      PCDFs were 2.4 times higher than those of PCDDs in this tissue. The absence of
      correlation between the quantity of dioxins and that of fat and the BCFs
      differences of theses congeners suggested that dioxins fixation process in the
      liver was selective.

PMID- 15992601
TI  - Dependence of mechanochemically induced decomposition of mono-chlorobiphenyl on
      the occurrence of radicals.
AB  - Mechanochemically induced dechlorination of mono-chlorobiphenyl (BP-Cl) on the
      surfaces of metal oxides was compared with that on metal hydroxides, using the
      three metals of Mg, Al, and La as examples. The metal oxides, such as gamma
      alumina (gamma-Al2O3), magnesium oxide (MgO) and lanthanum oxide (La2O3) showed
      an efficient ability to dechlorinate the BP-Cl; however, BP-Cl remained in the
      ground samples when the hydroxides were used. From the product analysis using gas
      chromatography/mass spectrometry (GC/MS) and electron spin resonance (ESR)
      measurements, it was confirmed that the charge transfer from the O2- site on the
      surface of the oxide additives due to the intense grinding has plays a
      significant role in the decomposition of the chlorinated compound. Based on the
      observed dependence of the dechlorination on the radical occurrence, some
      practical methods were proposed to improve the destruction efficiency of the
      chlorinated organic compounds.

PMID- 15992602
TI  - Influence of metal oxides on PCDD/Fs formation from pentachlorophenol.
AB  - Chlorophenols (ClPhs) are considered as important precursors for PCDD/Fs
      formation. The influences of series of metal oxides including MgO, Al2O3, CaO,
      BaO, TiO2, V2O5, MnO2, Fe2O3, Co3O4, CuO, Ag2O, ZnO, HgO, SnO, PbO, La2O3, CeO2,
      and Eu2O3 on PCDD/Fs formation from pentachlorophenol (PCP) were investigated in
      a laboratory-scale reactor. The results indicated that most of the above metal
      oxides have obvious suppressing effects on the total amount of PCDD/Fs formation
      from precursor PCP except for CuO, ZnO, MnO2, TiO2 and Co3O4 with promotion
      effects at 280 degrees C for 2 h. Although MgO, Al2O3, Fe2O3, PbO, La2O3 and
      Eu2O3 could reduce the amount of octachlorinated dibenzo-p-dioxin (OCDD), they
      promote the formation of more toxic 1,2,3,4,6,7,8-HpCDD at the same time. The
      total suppressing efficiencies of several metal oxides including CaO, BaO, PbO,
      Ag2O, HgO and SnO which have lower Z/r (charge to radius ratio) <2 are all over
      90%. The theories of generalized acid-base and atomic parameter (Z/r) were used
      to speculate the effecting mechanisms. The factors including time and temperature
      on suppressing efficiencies of CaO, BaO and PbO have also been studied in the
      present paper. The results showed that the total suppressing efficiencies of CaO,
      BaO and PbO increase with the increase of heated time and temperature.

PMID- 15992603
TI  - The role of soil organic carbon in the global cycling of persistent organic
      pollutants (POPs): interpreting and modelling field data.
AB  - Soil is an important global reservoir for persistent organic pollutants (POPs).
      The interaction between air (which often receives the majority of emissions) and
      soil plays a key role in the long term environmental cycling and fate of these
      chemicals. Soil surveys have been carried out to try and estimate regional and
      global distribution/inventory of POPs. A correlation between soil POPs
      concentration and soil organic carbon (SOC) has been observed in background soils
      [Meijer et al., 2003. Global distribution and budget of PCBs and HCB in
      background surface soils: implications for sources and environmental processes.
      Environ. Sci. Technol., 37, 667], provoking discussion about whether POPs will
      approach steady-state (or equilibrium) between air and SOC, on a global scale.
      This manuscript investigates this relationship and in particular how soil
      concentrations can be influenced by factors such as temperature, SOC content and
      physicochemical properties. A simple two box model designed to investigate
      parameters that are likely to affect air-soil exchange revealed that more
      volatile chemicals such as HCB are likely to achieve steady-state conditions
      between air and soil relatively quickly whilst relatively involatile chemicals,
      such as heavy PCBs, may take considerably longer and other compounds (e.g. OCDD)
      may never achieve it. These model calculations provide an insight into which fate
      processes (e.g. volatilisation or degradation) may control a chemicals fate in
      the terrestrial environment. A different modelling exercise was used to explore
      the complex interaction of environmental parameters, representative of 'real
      world' conditions to study their potential influence on POPs cycling at the
      European scale. Results from the model suggested that compound degradation rates
      in soil (linked to SOC content), temperature, vegetation cover and ecosystem C
      turnover are all likely to significantly influence POP air-soil exchange and
      fate.

PMID- 15992604
TI  - Statistical investigation of polychlorinated dibenzo-p-dioxins and dibenzofurans
      in the ambient air of Houston, Texas.
AB  - Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (dioxins and
      furans) are persistent, bioaccumulative and highly toxic chemical constituents
      that appear in the environment at very low and difficult to measure levels.
      Although dioxins and furans are widely recognized as toxic contaminants needing
      regulation, their temporal and spatial concentration profiles and the factors
      impacting their partitioning and congener distribution are only moderately
      understood. This paper presents the results from one of the most extensive
      ambient air dioxin and furan sampling efforts conducted in a geographic area to
      date. The data consist of monthly ambient concentrations of 17 of the most toxic
      congeners of dioxins and furans collected at five locations in Houston, Texas
      over a calendar year. The results showed a total annual mean dioxin and furan
      congener concentration of 1047 fg/m3 and an annual mean summation operatorI-TEQ
      concentration of 15 fg I-TEQ/m3 (16 fg WHO-TEQ/m3). These results, when compared
      with proximate data from the USEPA National Dioxin Ambient Monitoring Network
      (NDAMN), revealed significant (at the P0.05 level) differences between Houston
      and the NDAMN sites, suggesting the existence of local dioxin sources. A temporal
      analysis of the data showed that the congener concentration distribution varies
      over time, depending on the level of chlorination, type of congener, and
      temperature. The results also suggested that the fluctuations of congener
      concentrations and I-TEQ concentrations are closely correlated with minimum
      relative humidity, mean temperature, and mean NOx concentration.

PMID- 15992605
TI  - GC/MS analysis of polynuclear aromatic hydrocarbons in sediment samples from the
      Niger Delta region.
AB  - Thirteen sediment samples from different locations in the Niger Delta region of
      Nigeria were analyzed for the presence of 16 polynuclear aromatic hydrocarbons
      (PAHs) via gas chromatography/mass spectrometry. The specific target compounds
      for this study included naphthalene, acenaphthylene, acenaphthene, flourene,
      phenanthrene, anthracene, flouranthene, pyrene, benz[a]anthracene, chrysene,
      benzo[b]fluoranthene, benzo[k]flouranthene, benzo[a]pyrene, benzo[ghi]perylene,
      dibenz[a,h]anthracene, and indeno[1,2,3-cd]pyrene. Four isotopically labeled
      polynuclear aromatic hydrocarbons (acanaphthene-d10, phenanthrene-d10, chrysene
      d12 and perylene-d12) were used for internal standardization. All 16 PAHs were
      found in most of the thirteen samples with concentration ranging from 0.1
      microg/kg to 28 microg/kg. It was also found that the 5 and 6-ring PAHs were
      present in higher concentrations than all the other compounds, indicating their
      high resistance to microbial degradation.

PMID- 15992606
TI  - Dioxin hot spots in Vietnam.

PMID- 15992607
TI  - p66(shc) is highly expressed in fibroblasts from centenarians.
AB  - p66(shc-/-) mice exhibit prolonged lifespan and increased resistance to oxidative
      and hypoxic stress. To investigate p66(shc) involvement in human longevity,
      p66(shc) mRNA and protein were evaluated in fibroblasts from young people,
      elderly and centenarians, exposed to oxidative or hypoxic stress. Unexpectedly,
      centenarians showed the highest basal levels of p66(shc). Oxidative stress
      induced p66(shc) in all samples. At variance, hypoxic stress caused p66(shc)
      reduction only in cells from centenarians. These changes occurred in absence of
      any modification of p66(shc) promoter methylation pattern. Intriguingly, in cells
      from centenarians, p66(shc) induction was affected by p53 codon 72 polymorphism.
      Thus, cells from centenarians present a peculiar regulation of p66(shc),
      suggesting that its role in mammalian longevity is more complex than previously
      thought.

PMID- 15992608
TI  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase deregulation and age-related
      hypercholesterolemia: a new role for ROS.
AB  - The microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR)
      is the rate-limiting enzyme in cholesterol synthesis and is highly regulated by a
      variety of factors. We have recently reported increased reductase activity during
      ageing, attributed to a higher activation state and impaired degradation of the
      hepatic enzyme. One of the widely recognized causes of age-related metabolic
      modifications is the large increase of reactive oxygen species (ROS). Therefore,
      the effect of ROS increase on the activity and the regulation of the HMGCoAR has
      been investigated in two different experimental models of ROS enriched tissue:
      liver from rats fed on diets deprived of either Vitamin E (Vit. E) or
      polyunsaturated fatty acids (Pufa). The results show that in these models,
      compared to that of old rats, full activation the HMGCoAR was detected while a
      different degradation rate is observed with the respect to old rats. Thus, our
      data show full correlation between ROS production and increased HMGCoAR activity.
      The possible therapeutic implications of these results are discussed.

PMID- 15992609
TI  - Poor fetal growth followed by rapid postnatal catch-up growth leads to premature
      death.
AB  - It is widely accepted that individuals with a low birth weight are at increased
      risk of developing type 2 diabetes, insulin resistance and cardiovascular
      disease. This risk is amplified if the poor fetal growth is followed by rapid
      postnatal catch-up growth. We have shown recently that poor fetal growth,
      resulting from maternal protein restriction, followed by postnatal catch-up
      growth is associated with reduced average longevity in mice. Here, we show that
      in addition to reduced average longevity, mice which have been growth restricted
      in utero and then grown rapidly during the lactation period have a reduced
      maximum longevity. Maximum longevity of these mice was, further, reduced when the
      animals were weaned onto an obesity-inducing cafeteria-style diet. This reduced
      maximum longevity was associated with early age-related weight loss. These
      results demonstrate that maternal nutrition during critical periods of
      development has a major impact on quantity as well as quality of life.

PMID- 15992610
TI  - The impact of telomere erosion on memory CD8+ T cells in patients with X-linked
      lymphoproliferative syndrome.
AB  - Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T
      cell proliferation after primary Epstein-Barr virus (EBV) infection, due to
      mutations in the signalling lymphocyte activation molecule (SLAM) associated
      protein (SAP) molecule. We examined the impact of dysfunctional proliferative
      control on the extent of CD8+ T cell differentiation in XLP patients who
      recovered from primary EBV infection. Although these young patients have normal
      numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were
      extremely differentiated as defined by loss of CCR7 and CD27, low telomerase
      activity and very short telomeres. This was not a direct effect arising from the
      loss of SAP, but was due to excessive T cell stimulation due to this defect.
      Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase
      (hTERT), but not SAP, prevented telomere loss and considerably extended
      proliferative lifespan in vitro. These results indicate that excessive
      proliferation in CD8+ T cells in XLP patients may lead to end-stage
      differentiation and loss of functional EBV-specific CD8+ T cells through
      replicative senescence. This may contribute to the defective immunity found in
      XLP patients who survive acute EBV infection who develop EBV-related B cell
      lymphomas before the fourth decade of life.

PMID- 15992611
TI  - 1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and
      cerebral ischaemia in old type 2 diabetes-atherosclerotic patients.
AB  - Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular
      disease complications, such as myocardial infarction (MI) or stroke from plaque
      rupture. Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits
      collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and
      dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in
      atherosclerotic plaques might lead to plaque instability and rupture caused by
      chronic inflammation, which up-regulates the expression of pro-inflammatory
      cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI
      site lying in the coding region at position 1267 of the HSP70-2 gene have shown
      that the BB genotype is associated with NIDDM. We screened 60 old NIDDM patients
      with carotid stenosis and 107 old healthy controls for 1267 HSP70-2 polymorphism
      in order to establish if an association with plaque frailty exists. Different
      genotypic distributions were observed between patients and healthy controls. An
      increased relative risk was associated with the B allele (p = 0.0107; odds ratio
      = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques
      and serum levels of triglyceride, total cholesterol and LDL cholesterol were
      tested from patients stratified according to their B+ (AB and BB) and B- (AA)
      genotypes. Plaque morphology (soft or fibrous-calcified) and the incidence of
      cerebral ischaemia were also assessed. B+ patients showed increased HSP70-2, IL
      6, IFN-gamma, TNF-alpha and dyslipidemia as compared to B- carriers. The
      frequency of soft plaques increased in B+ in comparison to B- patients (67%
      versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral
      ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in B
      genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP70-2
      polymorphism may be of use in identifying B+ NIDDM patients at risk for carotid
      plaque rupture and cerebral ischaemia.

PMID- 15992612
TI  - Age-dependent change in Vitamin C status: a phenomenon of maturation rather than
      of ageing.
AB  - Several reports have shown that Vitamin C is depleted in animals with age. Based
      mainly on comparisons between young animals that have not yet reached maturity
      and old animals, it appears to be the general assumption that the change in
      Vitamin C status occurs at a late stage in life and that this phenomenon may
      either contribute to or result from the ageing process. In the present study,
      young (3 months old, n = 8) and old (36 months old, n = 8) female guinea pigs
      were followed for 6 months with monthly blood samplings and monitored for Vitamin
      C status as measured by plasma ascorbate and erythrocyte ascorbate recycling
      capacity after which the animals were euthanized. While remaining unchanged in
      the old animals, plasma Vitamin C status of the young animals significantly
      declined to that of the old animals within 3 months. During the following 3
      months, the Vitamin C status of the young animals remained unchanged.
      Furthermore, post mortem Vitamin C analyses of the animals now aged 9 and 42
      months, respectively, showed no effect of age on Vitamin C in plasma, liver,
      kidney, heart and brain between the groups while concentrations were
      significantly increased in cerebrospinal fluid and lung with age (p < 0.05).
      Moreover, a significantly elevated ascorbic acid oxidation ratio was observed in
      young compared to old animals (p < 0.05). The present data suggest that the
      decline in Vitamin C status with age occur early in life and is a phenomenon of
      maturation rather than of ageing. Data from other species and humans are
      discussed.

PMID- 15992613
TI  - Optimization of medium composition for the production of a probiotic
      microorganism, Lactobacillus rhamnosus, using response surface methodology.
AB  - This study was undertaken to optimize yeast extract, glucose, and vitamin
      concentrations; and also culture pH for maximizing the growth of a probiotic
      bacterium, Lactobacillus rhamnosus, and to assess the effects of these factors by
      using response surface methodology. A central composite design was used as an
      experimental design for the allocation of treatment combinations. A polynomial
      regression model with cubic and quartic terms was used for analysis of the
      experimental data. It was found that the effects involving yeast extract,
      glucose, vitamins and pH on the growth of L. rhamnosus were significant, and the
      strongest effect was given by the yeast extract concentration. Estimated optimum
      conditions of the factors for the growth of L. rhamnosus are as follows: pH=6.9;
      vitamin solution=1.28% (v/v); glucose=5.01% (w/v) and yeast extract=6.0% (w/v).

PMID- 15992614
TI  - Analysis of kimchi microflora using denaturing gradient gel electrophoresis.
AB  - A polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
      technique was used to determine the microfloral composition during the
      fermentation of kimchi, a traditional Korean fermented vegetable food. The kimchi
      was fermented at 10 degrees C or 20 degrees C for 30 or 20 days, respectively.
      DGGE of the partially amplified 16S rDNA was performed and the most intense bands
      sequenced. The application of this culture-independent molecular technique
      determined that the lactic acid bacteria Weissella confusa, Leuconostoc citreum,
      Lactobacillus sakei, and Lactobacillus curvatus were the main microorganisms
      responsible for kimchi fermentation.

PMID- 15992615
TI  - The occurrence of Vibrio species in tropical shrimp culture environments;
      implications for food safety.
AB  - The occurrence of various Vibrio species in water, sediment and shrimp samples
      from multiple shrimp farm environments from the east and west coast of India was
      studied. The relative abundance was higher in west coast farms (ca. 10(4) cfu/ml
      water) when compared to the east coast (ca. 10(2) cfu/ml water). Vibrio
      alginolyticus (3-19%), V. parahaemolyticus (2-13%), V. harveyi (1-7%) and V.
      vulnificus (1-4%) were the predominant Vibrio species identified by standard
      biochemical testing. In some cases, V. cholerae could be found, but all isolates
      were negative for the cholera toxin (ctx) gene that is associated with
      choleragenic strains. The biochemical identification of V. parahaemolyticus, the
      other human pathogen among the species mentioned above, was confirmed by PCR
      targeting the toxR gene and a 387 bp chromosomal locus specific for this species.
      Furthermore, the presence of the virulence-associated tdh (thermostable direct
      haemolysin) and trh (TDH-related haemolysin) genes in the V. parahaemolyticus
      isolates was also detected by PCR. Only 2 out of 47 isolates were tdh positive
      and one contained the trh gene. However, since V. cholerae, V. parahaemolyticus
      and V. vulnificus species are recognized as a major cause of seafood-borne
      illness, it is important to pay attention to post-harvest handling and adequate
      cooking.

PMID- 15992616
TI  - Engineering of an oenological Saccharomyces cerevisiae strain with pectinolytic
      activity and its effect on wine.
AB  - A pectinolytic industrial yeast strain of Saccharomyces cerevisiae was generated
      containing the S. cerevisiae endopolygalacturonase gene (PGU1) constitutively
      expressed under the control of the 3-phosphoglycerate kinase gene (PGK1)
      promoter. The new strain contains DNA derived exclusively from yeast and
      expresses a high polygalacturonic acid hydrolyzing activity. Yeast transformation
      was carried out by an integrative process targeting a dispensable upstream region
      of the acetolactate synthase locus (ILV2), which determines sulfometuron methyl
      resistance. Microvinification assays were performed on white and red musts with
      the transformed UCLMS-1M strain and with the same strain untransformed. It was
      found that the changes in the pectic polysaccharide contents did not directly
      affect the taste or flavor of the wine. From the data reported, it is deduced
      that the chief advantage of using the modified strain is that it improves the
      yield of must/wine extraction, while it also positively affects some variables
      relating to appearance.

PMID- 15992617
TI  - Antagonistic activity against Salmonella infection in vitro and in vivo for two
      Lactobacillus strains from swine and poultry.
AB  - In this study, we isolated two lactobacillus strains, i.e., strain LAP5 and LF33,
      from swine and poultry, respectively, and showed that both strains were acid as
      well as bile tolerant and were able to adhere to the cultured human intestinal
      cell lines, such as Int-407 and Caco-2 cells, and to the intestinal epithelium
      cells isolated from swine, poultry and mouse (BALB/c). Both of these LAB strains
      were shown to inhibit the growth of Escherichia coli, Salmonella typhimurium,
      Staphylococcus aureus and Bacillus cereus. When these two LAB strains were
      evaluated for their antagonistic activity against Salmonella (S. typhimurium)
      invasion to cultured human intestinal cell line Int-407 and to mouse (BALB/c)
      liver and spleen, these two LAB strains were found to have significant
      antagonistic effect.

PMID- 15992618
TI  - Increased tolerance of Vibrio cholerae O1 to temperature, pH, or drying
      associated with colonization of shrimp carapaces.
AB  - External surfaces of samples of shrimp carapace were inoculated with Vibrio
      cholerae and stored at 22 degrees C for 1 h in a moist environment to facilitate
      their adhesion, or for 24 h to permit their colonization of the material.
      Colonizing cells showed a higher resistance to the effects of high temperatures,
      low pH, and desiccation conditions than adherent cells. Periods of 10, 5, and 3
      min and 0 s were required to inactivate the pathogen when attached cells were
      exposed to 50, 60, 65, or 70 degrees C. The corresponding times for colonizing
      cells were 30, 15, 10, and 1 min. At pH 2.5 numbers of attached V. cholerae were
      reduced by >5 log after 16 min, whereas the reduction of colonizing cells was
      only 2.8 log. The survival times of the microorganism on dried carapaces stored
      at 5 and 22 degrees C were, respectively, 60 and 10 min for adherent cells, and
      12 and 4 h for colonizing cells. The increased resistance to the effects of high
      temperatures, low pH, and desiccation of V. cholerae O1 colonizing shrimp
      carapaces may have significant implications for food safety and the epidemiology
      of cholera.

PMID- 15992619
TI  - Detection of the apr gene in proteolytic psychrotrophic bacteria isolated from
      refrigerated raw milk.
AB  - Bacteria of the genus Pseudomonas have been associated with the spoilage of raw
      milk and dairy products due to the production of thermostable proteolytic
      enzymes. The apr gene encodes for alkaline metalloprotease in Pseudomonas and
      other related bacteria. Its presence in psychrotrophic proteolytic bacteria
      isolated from raw milk collected from cooling tanks was verified. A polymerase
      chain reaction (PCR) technique was used with degenerate primers. Total DNA from
      112 isolates was pooled in different groups and then used as template for the
      amplification reactions. Controls consisted of DNA extracted from 26 cultures. An
      expected DNA fragment of 194 bp was detected in groups that contained bacteria
      identified as Pseudomonas. The PCR product was observed only when DNA from
      control cultures of Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia
      marcescens and Aeromonas hydrophila were used. A detection limit assay indicated
      that the apr gene could be directly amplified from pasteurized milk inoculated
      with 10(8) CFU/ml of P. fluorescens. With this method it was possible to detect
      proteolytic bacteria at 10(5) CFU/ml in reconstituted skim milk powder if cells
      were recovered for DNA extraction before amplification.

PMID- 15992620
TI  - Antibacterial activity of propolis against Staphylococcus aureus.
AB  - In the present study, antimicrobial activity of the ethanolic extract of propolis
      (EEP), collected at different periods (June, August, and October-November) from
      various regions (Taipei, Mingchien, and Fanglia) in Taiwan, against
      Staphylococcus aureus was investigated. The effects of cell age, incubation
      temperature, and pH in response to EEP were also investigated. Depending on
      concentration, collecting area, and time, EEP exerted various degrees of
      antibacterial activity against S. aureus. The minimum inhibitory concentration of
      EEP tested ranged from <3.75 to 60 microg/ml, while the minimum bactericidal
      concentration ranged between 7.5 and 120 microg/ml against S. aureus. In general,
      a higher antibacterial activity was noted with EEP collected in August than other
      months. EEP of Mingchien-6 showed the most profound antibacterial activity among
      the EEP samples tested. The age of a bacterial culture affected its
      susceptibility to EEP. Cells in the late-exponential phase were most susceptible
      to EEP. Higher temperature (37 degrees C) and acidic pH enhanced the
      antibacterial activity of EEP.

PMID- 15992621
TI  - Culture-dependent and culture-independent qualitative analysis of probiotic
      products claimed to contain bifidobacteria.
AB  - A total of 58 probiotic products obtained worldwide, which were claimed to
      contain Bifidobacterium strains (including 22 yoghurts, 5 dairy fruit drinks, 28
      food supplements and 3 pharmaceutical preparations) were investigated in parallel
      using a culture-dependent and a culture-independent approach. Three isolation
      media previously reported as selective for Bifidobacterium were evaluated for
      their suitability in the quality analysis of these products. Subsequently,
      possible bifidobacterial colonies were picked from the best medium and identified
      by means of rep-PCR fingerprinting using the BOX primer (BOX-PCR).
      Bifidobacterium animalis subsp. lactis, formerly classified as Bifidobacterium
      lactis, was most frequently found, but strains belonging to Bifidobacterium
      longum biotypes longum and infantis, Bifidobacterium bifidum and Bifidobacterium
      breve were recovered also. In parallel, all products were also subjected to
      culture-independent analysis which involved a nested-PCR step on total bacterial
      DNA extracted directly from the product, followed by separation of the amplicons
      by Denaturing Gradient Gel Electrophoresis (DGGE) and subsequent identification
      of species from the band patterns. By conventional cultivation, 70.7% of the
      products analysed were found to contain culturable bifidobacteria whereas by
      culture-independent DGGE analysis members of the genus Bifidobacterium could be
      detected in 96.5% of the analysed products. Genotypic characterization of a
      number of bifidobacterial isolates at the strain level by means of Pulsed-Field
      Gel Electrophoresis (PFGE) revealed a relatively high degree of genomic
      homogeneity among the Bifidobacterium strains currently used in the probiotic
      industry.

PMID- 15992622
TI  - Use of traditional African fermented beverages as delivery vehicles for
      Bifidobacterium lactis DSM 10140.
AB  - A microencapsulation delivery system for Bifidobacterium lactis, a possible
      probiotic suited for use by the rural population of South Africa, was evaluated
      using two existing traditional fermented foods, amasi and mahewu. Gellan/xanthan
      microcapsules containing viable B. lactis, were tested under simulated
      physiological conditions, and added to pasteurized beverages. The capsules
      protected the organism under simulated low pH conditions associated with the
      stomach and from the biocidal activity of pancreatic and bile acids. For mahewu,
      microencapsulation of B. lactis with storage aerobically at 4 degrees C and 22
      degrees C enhanced survival over a 21-day period as compared to free cells. In
      amasi, differences in viability between immobilized and free cells were less
      noticeable. An analytically trained taste panel was unable to detect a
      significant difference in texture in any of the samples fortified with
      microcapsules. Although flavour differences were noted for mahewu containing
      either free or immobilized cells, after 14 days refrigerated storage, these were
      not disliked. No significant flavour difference was noted between amasi
      containing immobilized cells and untreated controls over the period tested.

PMID- 15992623
TI  - Enterococci from Tolminc cheese: population structure, antibiotic susceptibility
      and incidence of virulence determinants.
AB  - Microbiological analysis of ripened artisanal Tolminc cheese revealed the
      presence of an enterococcal population in numbers of up to 10(6) per g. All
      colonies, isolated from the citrate azide tween carbonate (CATC) enterococcal
      selective medium were Gram positive and coccal-shaped and were analysed with
      PhenePlate FS system. This system discriminated 10 PhP clusters among the 90
      enterococcal isolates. From each cluster the most representative isolate for that
      particular type was selected for further study. The 10 representative enterococci
      were catalase negative and grew in the presence of NaCl (2%, 4% and 6.5%) and
      bile salts (0.06%). Genus specific primers confirmed all 10 enterococcal
      representatives as Enterococcus members, while species specific primers
      determined them further as strains of Enterococcus faecalis species. PCR for vanA
      and vanB genes detection, respectively, amplified no PCR products. The absence of
      van genes was confirmed with both disc and E-test, as isolates were susceptible
      to vancomycin according to the National Committee for Clinical Laboratory
      Standards (NCCLS). The results of disc tests with other antimicrobial agents
      (ampicillin, vancomycin, kanamycin, penicillin, erythromycin, neomycin,
      chloramphenicol, clindamycin, rifampin) did not differ much among the tested
      enterococci: they were all very resistant to clindamycin only. The incidence of
      enterococcus virulence determinants was as expected: all of the 10 E. faecalis
      strains tested possessed multiple determinants (between 7 and 11).

PMID- 15992624
TI  - Cases of emesis associated with bacterial contamination of an infant breakfast
      cereal product.
AB  - A commercial product for infants containing cereal mixed with dried infant
      formula was diagnosed as producing rapid projectile vomiting in two infants.
      Analysis of multiple samples of the cereal product revealed significant
      contamination with two spore-forming species, Bacillus subtilis and a strain of
      Bacillus cereus. The latter is the most likely cause of the emetic food
      poisoning, but we were unable to detect B. cereus emetic toxin. This raises the
      possibility of the cause being either a new cereulide-type toxin, or the
      bacterial load, in which case the presence of B. subtilis could have been a
      contributing factor.

PMID- 15992626
TI  - Novel insights into the regulation of the viral polymerase complex of neurotropic
      Borna disease virus.
AB  - Borna disease virus (BDV) genetic information is encoded in a highly condensed
      non-segmented RNA genome of negative polarity. Replication and transcription of
      the genome occurs in the nucleus, enabling the virus to employ the cellular
      splicing machinery to process primary transcripts and to regulate expression of
      viral gene products. BDV establishes a non-cytolytic, persistent infection that
      in animals is mainly restricted to neurons of the central nervous system. Based
      on these unique properties, BDV represents the prototype member of the virus
      family Bornaviridae in the order Mononegavirales. Analysis of molecular aspects
      of BDV replication has long been hampered by the lack of a reverse genetics
      system. Only recently, artificial BDV minigenomes permitted the reconstitution of
      the viral polymerase complex, allowing finally the recovery of BDV from cDNA. As
      in other families of the Mononegavirales, the active polymerase complex of BDV is
      composed of the polymerase (L), the nucleoprotein (N) and the phosphoprotein (P).
      In addition, the viral X protein was identified as potent negative regulator of
      polymerase activity. Protein interaction studies combined with minireplicon
      assays suggested that P is a central regulatory element of BDV replication that
      directs the assembly of the polymerase complex. Most intriguingly, BDV obtained
      from cDNA with variable genomic termini suggests a novel strategy for viral
      replication-control. BDV seems to restrict its propagation efficacy by defined 5'
      terminal trimming of genomic and antigenomic RNA molecules. This review will
      summarize these novel findings and will discuss them in the context of BDV
      neurotropism and persistence.

PMID- 15992627
TI  - The adult with congenital heart disease: born to be bad?
AB  - The population of patients with adult congenital heart disease is approximately
      800,000 in the U.S. Those with prior cardiac surgery often consider themselves
      "cured," although the majority faces a lifetime of problems including
      arrhythmias, ventricular dysfunction, and one or more re-operations. Even
      patients with repaired "simple" lesions such as an atrial septal defect may not
      have normal survival if they are repaired in adulthood. Patients with repaired
      coarctation may have premature cardiovascular complications including sudden
      cardiac death, myocardial infarction, and stroke. They also have aortic
      complications such as aneurysm and dissection, which result from a diffuse
      arteriopathy and continued hypertension that may be caused by underlying
      endothelial dysfunction. In addition, bicuspid aortic valve occurs in more than
      one-half of the patients with coarctation, so continued surveillance for
      significant aortic valvular heart disease is necessary. More complex lesions also
      pose problems after "total correction." Patients with repaired tetralogy of
      Fallot often have pulmonary regurgitation, which is frequently overlooked on
      clinical exam and echocardiography. Pulmonary valve replacement should be
      performed before the development of irreversible right ventricular dysfunction
      and an increased risk of ventricular tachycardia or sudden cardiac death. Because
      they are vulnerable to deterioration of systemic ventricular function, those with
      congenitally corrected transposition require special vigilance, usually with
      concomitant atrio-ventricular valve regurgitation. Late referral is common with a
      deleterious effect on long-term survival. These patients need lifelong follow-up
      and the residua and sequelae of their complex anomalies must be understood in
      order to provide optimum care.

PMID- 15992628
TI  - Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to
      prevent stroke in high-risk patients with non-rheumatic atrial fibrillation:
      results from the international multi-center feasibility trials.
AB  - OBJECTIVES: These studies were conducted to evaluate the feasibility of
      percutaneous left atrial appendage (LAA) occlusion using the PLAATO system (ev3
      Inc., Plymouth, Minnesota). BACKGROUND: Patients with atrial fibrillation (AF)
      have a five-fold increased risk for stroke. Other studies have shown that more
      than 90% of atrial thrombi in patients with non-rheumatic AF originate in the
      LAA. Transvenous closure of the LAA is a new approach in preventing embolism in
      these patients. METHODS: Within two prospective, multi-center trials, LAA
      occlusion was attempted in 111 patients (age 71 +/- 9 years). All patients had a
      contraindication for anticoagulation therapy and at least one additional risk
      factor for stroke. The primary end point was incidence of major adverse events
      (MAEs), a composite of stroke, cardiac or neurological death, myocardial
      infarction, and requirement for procedure-related cardiovascular surgery within
      the first month. RESULTS: Implantation was successful in 108 of 111 patients
      (97.3%, 95% confidence interval [CI] 92.3% to 99.4%) who underwent 113
      procedures. One patient (0.9%, 95% CI 0.02% to 4.9%) experienced two MAEs within
      the first 30 days: need for cardiovascular surgery and in-hospital neurological
      death. Three other patients underwent in-hospital pericardiocentesis due to a
      hemopericardium. Average follow-up was 9.8 months. Two patients experienced
      stroke. No migration or mobile thrombus was noted on transesophageal
      echocardiogram at one and six months after device implantation. CONCLUSIONS:
      Closing the LAA using the PLAATO system is feasible and can be performed at
      acceptable risk. It may become an alternative in patients with AF and a
      contraindication for lifelong anticoagulation treatment.

PMID- 15992629
TI  - Sustained benefit 20 years after reperfusion therapy in acute myocardial
      infarction.
AB  - OBJECTIVES: The goal of this research was to clarify whether the benefit of
      reperfusion therapy for myocardial infarction was sustained long-term and to
      assess the gain in life expectancy by reperfusion therapy. BACKGROUND:
      Reperfusion therapy in acute myocardial infarction reduces infarct size and
      increases hospital survival. METHODS: We analyzed the 20-year outcome of 533
      patients (mean age 56 years; 82% men) who were randomized to either reperfusion
      therapy or conventional therapy during the years 1981 to 1985. RESULTS: Mean
      follow-up was 21 years (range 19 to 23 years). At follow-up, 101 patients (36%)
      of the 269 patients allocated to reperfusion treatment and only 71 patients (26%)
      of the 264 conventionally treated patients were alive (p = 0.02). The cumulative
      10-, 15-, and 20-year survival rates were 69%, 48%, and 37% after reperfusion
      therapy and 59%, 38%, and 27% in the control group, respectively (p = 0.005).
      Life expectancy of the reperfusion group was 15.2 years versus 12.4 years in the
      conventionally treated group (p < 0.0001). Myocardial re-infarction and
      subsequent coronary interventions were more frequent after reperfusion therapy,
      particularly during the first year. In multivariable analysis, reperfusion
      therapy was an important independent predictor of lower mortality at long-term
      follow-up (hazard ratio 0.7; 95% confidence interval 0.6 to 0.8). Other
      independent predictors of mortality were age, impaired left ventricular function,
      multivessel disease, infarct size, and inability to perform an exercise test at
      the time of discharge. CONCLUSIONS: This is the first study demonstrating
      sustained (20-year) improved survival after reperfusion therapy. The gain in life
      expectancy was almost three years, representing about one-third of the life-years
      lost by myocardial infarction.

PMID- 15992630
TI  - Coagulopathy after successful cardiopulmonary resuscitation following cardiac
      arrest: implication of the protein C anticoagulant pathway.
AB  - OBJECTIVES: We investigated coagulation abnormalities in out-of-hospital cardiac
      arrest (OHCA) patients, with special attention to the protein C anticoagulant
      pathway. BACKGROUND: Successfully resuscitated cardiac arrest is followed by a
      systemic inflammatory response and by activation of coagulation, both of which
      may contribute to organ failure and neurological dysfunction. METHODS:
      Coagulation parameters were measured in all patients admitted after successfully
      resuscitated OHCA. RESULTS: At admission, 67 patients had a systemic inflammatory
      response with increased interleukin-6 and coagulation activity (thrombin
      antithrombin complex), reduced anticoagulation (antithrombin, protein C, and
      protein S), activated fibrinolysis (plasmin-antiplasmin complex), and, in some
      cases, inhibited fibrinolysis (increased plasminogen activator inhibitor-1 with a
      peak on day 1). These abnormalities were more severe in patients who died within
      two days (50 of 67, 75%) and were most severe in patients dying from early
      refractory shock. Protein C and S levels were low compared to healthy volunteers
      and discriminated OHCA survivors from nonsurvivors. Furthermore, a subgroup of
      patients had a transient increase in plasma-activated protein C at admission
      followed by undetectable levels. This, along with an increase in soluble
      thrombomodulin over time, suggests secondary endothelial injury and dysfunction
      of the protein C anticoagulant pathway similar to that observed in severe sepsis.
      CONCLUSIONS: Major coagulation abnormalities were found after successful
      resuscitation of cardiac arrest. These abnormalities are consistent with
      secondary down-regulation of the thrombomodulin-endothelial protein C receptor
      pathway.

PMID- 15992631
TI  - Patients with prolonged ischemic chest pain and presumed-new left bundle branch
      block have heterogeneous outcomes depending on the presence of ST-segment
      changes.
AB  - OBJECTIVES: The purpose of this research was to examine the prognostic value of
      ST-segment changes (concordant ST-segment elevation and/or precordial V1 to V3 ST
      segment depression) during presumed-new left bundle branch block (LBBB) in
      patients receiving fibrinolytic therapy. BACKGROUND: These patients are often
      considered high-risk, but their outcome is not well-defined. METHODS: The Hirulog
      and Early Reperfusion or Occlusion (HERO)-2 trial compared bivalirudin with
      heparin in patients receiving streptokinase for ST-segment elevation or presumed
      new LBBB. Each patient with LBBB was matched with a control (with normal
      intraventricular conduction) for age, gender, pulse rate, systolic blood
      pressure, Killip class, and region. RESULTS: A total of 300 patients had LBBB (92
      with and 208 without ST-segment changes) and 15,340 had normal conduction. Acute
      myocardial infarction (AMI) occurred in 80.7% of LBBB patients and 88.7% of
      controls (p = 0.006). ST-segment changes were specific (96.6%) but not sensitive
      (37.8%) for enzymatic diagnosis of AMI. Mortality at 30 days was similar in LBBB
      patients with ST-segment changes (21.7%) and controls (25.0%, p = 0.563), but
      lower in LBBB patients without ST-segment changes than in controls (13.5% vs.
      21.6%, p = 0.022). In the whole HERO-2 cohort, the LBBB patients with ST-segment
      changes had higher mortality than patients with normal conduction (odds ratio
      [OR] 1.37, 95% confidence interval [CI] 0.78 to 2.42). The LBBB patients without
      ST-segment changes had lower mortality than patients with normal conduction (OR
      0.52, 95% CI 0.33 to 0.80). CONCLUSIONS: ST-segment changes during LBBB are
      specific for the diagnosis of AMI and predict 30-day mortality; LBBB patients
      without ST-segment changes have lower adjusted 30-day mortality than those with
      normal conduction. Trials are required to determine the best treatment for high
      risk and low-risk patients with LBBB.

PMID- 15992632
TI  - Left bundle branch block in acute myocardial infarction: benign or malignant?

PMID- 15992633
TI  - The effects of plasma insulin and glucose on myocardial blood flow in patients
      with type 1 diabetes mellitus.
AB  - OBJECTIVES: The objective of this study was to determine the impact of insulin
      and glucose on myocardial vasodilator function in patients with type 1 diabetes
      mellitus (T1DM). BACKGROUND: The relative importance of plasma insulin and
      glucose levels on the abnormal vasodilator function observed in T1DM is unknown.
      METHODS: Twenty T1DM patients underwent positron emission tomography studies to
      measure myocardial blood flow (MBF) (in ml/g/min) at rest (MBFr) and during
      adenosine (MBFa), both under baseline metabolic conditions and then during either
      hyperinsulinemic-euglycemic clamp (HE) (n = 10; 40 +/- 9 years, 8 female
      subjects, hemoglobin A1c [HbA1c] 7.8 +/- 1.1%) or hyperinsulinemic-hyperglycemic
      clamp (HH) (n = 10; 44 +/- 12 years, 8 female subjects, hemoglobin A1c 7.7 +/-
      0.6%). RESULTS: Both groups showed similar MBFr and MBFa under baseline metabolic
      conditions (p = NS). Compared with baseline conditions, MBFr increased in the HH
      group (p < 0.005), whereas it did not change in the HE group. Compared with
      baseline conditions, MBFa decreased in the HH group (p < 0.05) but did not change
      in the HE group. Myocardial perfusion reserve (MPR) (MBFa/MBFr) was similar
      between the HE and HH groups at baseline (p = NS). During clamp, MPR tended to
      decrease in the HH group (p < 0.1) but did not change in the HE group (p = NS)
      when compared with baseline conditions. However, during the clamp MPR was
      significantly lower in the HH group when compared with the HE group (p < 0.0001).
      CONCLUSIONS: In the short term, hyperglycemia has a deleterious effect on
      myocardial vasodilator function, which outweighs the beneficial effect of
      hyperinsulinemia.

PMID- 15992634
TI  - Glucose for the heart: too much of a good thing?

PMID- 15992635
TI  - Electrocardiographic predictors of cardiovascular outcome in women: the National
      Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation
      (WISE) study.
AB  - OBJECTIVES: We sought to analyze the value of infrequently measured parameters of
      the 12-lead electrocardiogram (ECG) in predicting cardiovascular events in women
      with suspected myocardial ischemia who were referred for cardiac catheterization.
      BACKGROUND: Routinely analyzed ECG parameters have low predictive value for
      cardiovascular events in women with preserved left ventricular function and
      suspected myocardial ischemia. The predictive value of ECG parameters for
      cardiovascular disease has not been fully determined. METHODS: Women enrolled in
      the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome
      Evaluation (WISE) study who had complete digital 12-lead ECG and quantitative
      angiography data were studied. Clinical and ECG predictors of cardiovascular
      disease events, defined as death, congestive heart failure, and non-fatal
      myocardial infarction, were determined. RESULTS: Of 143 women with ECG and
      angiographic data (mean age 59 +/- 13 years, left ventricular ejection fraction
      64.1 +/- 8.6%), 13% had events during a mean follow-up period of 3.3 +/- 1.6
      years. Independent predictors of event occurrences included a wider QRS-T angle
      (i.e., the spatial electrical angle between the QRS complex and the T-wave; p =
      0.0005), wider QRS complex (p = 0.004), longer QTrr (i.e., age- and gender
      adjusted QT interval; p = 0.0004), a more depressed ST-segment in precordial lead
      V5 (p = 0.0002), and a higher coronary artery disease severity score (p = 0.02).
      CONCLUSIONS: Several 12-lead ECG parameters, such as the QRS-T angle and the QRS
      and QTrr duration, are predictive of future cardiovascular events in women with
      suspected myocardial ischemia.

PMID- 15992636
TI  - In-hospital mortality in patients with acute decompensated heart failure
      requiring intravenous vasoactive medications: an analysis from the Acute
      Decompensated Heart Failure National Registry (ADHERE).
AB  - OBJECTIVES: We sought to compare the in-hospital mortality of patients with acute
      decompensated heart failure (ADHF) who were receiving parenteral treatment with
      one of four intravenous vasoactive medications. BACKGROUND: There are limited
      data regarding the effects of the choice of intravenous vasoactive medication on
      in-hospital mortality in patients hospitalized with ADHF. METHODS: This was a
      retrospective analysis of observational patient data from the Acute Decompensated
      Heart Failure National Registry (ADHERE), a multicenter registry designed to
      prospectively collect data on each episode of hospitalization for ADHF and its
      clinical outcomes. Data from the first 65,180 patient episodes (October 2001 to
      July 2003) were included in this analysis. Cases in which patients received
      nitroglycerin, nesiritide, milrinone, or dobutamine were identified and reviewed
      (n = 15,230). Risk factor and propensity score-adjusted odds ratios (ORs) for in
      hospital mortality were calculated. RESULTS: Patients who received intravenous
      nitroglycerin or nesiritide had lower in-hospital mortality than those treated
      with dobutamine or milrinone. The risk factor and propensity score-adjusted ORs
      for nitroglycerin were 0.69 (95% confidence interval [CI] 0.53 to 0.89, p < or =
      0.005) and 0.46 (94% CI 0.37 to 0.57, p < or = 0.005) compared with milrinone and
      dobutamine, respectively. The corresponding values for nesiritide compared with
      milrinone and dobutamine were 0.59 (95% CI 0.48 to 0.73, p < or = 0.005) and 0.47
      (95% CI 0.39 to 0.56, p < or = 0.005), respectively. The adjusted OR for
      nesiritide compared with nitroglycerin was 0.94 (95% CI 0.77 to 1.16, p = 0.58).
      CONCLUSIONS: Therapy with either a natriuretic peptide or vasodilator was
      associated with significantly lower in-hospital mortality than positive inotropic
      therapy in patients hospitalized with ADHF. The risk of in-hospital mortality was
      similar for nesiritide and nitroglycerin.

PMID- 15992637
TI  - Acute decompensated heart failure: the shrinking role of inotropic therapy.

PMID- 15992638
TI  - The coronary venous anatomy: a segmental approach to aid cardiac
      resynchronization therapy.
AB  - The coronary sinus is the gateway for left ventricular (LV) epicardial lead
      placement for cardiac resynchronization therapy. The implanting
      electrophysiologist is usually challenged by a high degree of variability in the
      coronary venous anatomy, making it important to have a more consistent and
      uniform segmental approach to describe the coronary venous tree and its branches.
      Classifying the coronary sinus branches and tributaries by the segment of their
      location rather than by conventional anatomic names (i.e., middle cardiac vein,
      great cardiac vein, and so on), would provide more relevant anatomic and
      functional information at the time of LV lead placement. This would enable the
      implanting physician to proactively correlate the venous anatomy with the
      segmental wall motion abnormalities or dyssynchrony, as defined by
      echocardiography and other imaging modalities. The current viewpoint calls for a
      more systematic segmental approach for describing the coronary venous anatomy.

PMID- 15992639
TI  - Microvolt T-wave alternans for the risk stratification of ventricular
      tachyarrhythmic events: a meta-analysis.
AB  - OBJECTIVES: The objective of this study was to perform a meta-analysis of the
      predictive value of microvolt T-wave alternans (MTWA) testing for arrhythmic
      events in a wide variety of populations. BACKGROUND: Previous studies describing
      the use of MTWA as a predictor of ventricular tachyarrhythmic events have been
      limited by small sample sizes and disparate populations. METHODS: Prospective
      studies of the predictive value of exercise-induced MTWA published between
      January 1990 and December 2004 were retrieved. Data from each article were
      abstracted independently by two authors using a standardized protocol. Summary
      estimates of the predictive value of MTWA were made using a random-effects model.
      RESULTS: Data were accumulated from 19 studies (2,608 subjects) across a wide
      range of populations. Overall, the positive predictive value of MTWA for
      arrhythmic events was 19.3% at an average of 21 months' follow-up (95% confidence
      interval [CI] 17.7% to 21.0%), the negative predictive value was 97.2% (95% CI
      96.5% to 97.9%), and the univariate relative risk of an arrhythmic event was 3.77
      (95% CI 2.39 to 5.95). There was no difference in predictive value between
      ischemic and nonischemic heart failure subgroups. The positive predictive value
      varied depending on the population of patients studied (p < 0.0001). CONCLUSIONS:
      Microvolt T-wave alternans testing has significant value for the prediction of
      ventricular tachyarrhythmic events; however, there are significant limitations to
      its use. The predictive value of MTWA varies significantly depending on the
      population studied. Careful standardization is needed for what constitutes
      abnormal MTWA. The incremental prognostic value of MTWA when used with other
      methods of risk stratification is unclear.

PMID- 15992640
TI  - Catheter ablation of atypical atrial flutter and atrial tachycardia within the
      coronary sinus after left atrial ablation for atrial fibrillation.
AB  - OBJECTIVES: The goal of this study was to describe the prevalence and ablation of
      coronary sinus (CS) arrhythmias after left atrial ablation for atrial
      fibrillation (AF). BACKGROUND: The CS has been implicated in a variety of
      supraventricular arrhythmias. METHODS: Thirty-eight patients underwent mapping
      and ablation of atypical flutter that developed during (n = 5) or after (n = 33)
      ablation for AF. Also included were two patients with focal CS arrhythmias that
      occurred during an AF ablation procedure. A tachycardia was considered to be
      originating from the CS if the post-pacing interval in the CS matched the
      tachycardia cycle length and/or if it terminated during ablation in the CS.
      RESULTS: Among the 33 patients who developed atypical flutter late after AF
      ablation, 9 (27%) were found to have a CS origin. Overall, 16 of the 40 patients
      in this study had a CS arrhythmia. The tachycardia was macro-re-entrant in 14
      patients (88%) and focal in two patients. Radiofrequency ablation with an 8-mm
      tip catheter was successful in 15 patients (94%) without complication. In eight
      patients (50%), > or = 45 W was required for successful ablation. Thirteen of the
      15 patients (87%) with a successful ablation acutely remained arrhythmia-free
      during 5 +/- 5 months of follow-up. CONCLUSIONS: The musculature of the CS serves
      as a critical component of the re-entry circuit in approximately 25% of patients
      with atypical flutter after ablation for AF. The CS may also generate focal
      atrial arrhythmias that may play a role in triggering and/or maintaining AF.
      Catheter ablation of these arrhythmias in the CS can be performed safely.

PMID- 15992641
TI  - Head-to-head comparison of three-dimensional navigator-gated magnetic resonance
      imaging and 16-slice computed tomography to detect coronary artery stenosis in
      patients.
AB  - OBJECTIVES: The purpose of this research was to compare the diagnostic accuracy
      of three-dimensional navigator-gated magnetic resonance (MR) imaging and 16-slice
      multidetector row computed tomography (MDCT) versus quantitative coronary
      angiography (QCA) for the detection of coronary artery stenosis in patients.
      BACKGROUND: Both MR and MDCT are novel non-invasive tests, which have been
      proposed for noninvasive detection of coronary artery disease. Yet their
      diagnostic accuracy has not been directly compared in the same population.
      METHODS: Fifty-two patients underwent coronary MR and 16-slice MDCT before
      invasive coronary angiography. Diameter stenosis (DS) severity in vessels >1.5-mm
      reference diameter were graded visually and measured quantitatively on both MR
      and MDCT images. Diagnostic accuracy of both methods was compared using QCA as
      the reference test. RESULTS: According to QCA, 81 of 452 (18%) coronary segments
      with >1.5 mm diameter had >50% DS. By visual analysis, MR and MDCT had similar
      sensitivity (75% vs. 82%, p = NS), specificity (77% vs. 79%, p = NS), and
      diagnostic accuracy (77%, vs. 80%, p = NS) for detection of >50 % DS.
      Quantitative measures of DS by MR (r = 0.60, p < 0.001) and MDCT (r = 0.75, both
      p < 0.001) correlated well with QCA. Receiver-operating characteristic analysis
      demonstrated that quantification of DS severity improved the diagnostic accuracy
      of MDCT (area under curve [AUC] 0.81 vs. 0.92, p < 0.001) but not that of MR (AUC
      0.78 vs. 0.83, p = NS). CONCLUSIONS: Visual assessment of coronary diameter
      stenosis severity by MR or MDCT allows identification of significant coronary
      artery disease with a similar high diagnostic accuracy. Quantitative analysis
      significantly further improves the diagnostic accuracy of MDCT but not that of
      MR.

PMID- 15992642
TI  - Left ventricular non-compaction: insights from cardiovascular magnetic resonance
      imaging.
AB  - OBJECTIVES: We aimed to test the diagnostic accuracy of cardiovascular magnetic
      resonance (CMR) imaging in distinguishing pathological left ventricular non
      compaction (LVNC) from lesser degrees of trabecular layering seen in healthy
      volunteers and, in those with cardiomyopathies and concentric left ventricular
      hypertrophy, potential differential diagnoses. We hypothesized that pathological
      trabeculation could be distinguished by determining the ratio of non-compacted to
      compacted myocardium (NC/C ratio). BACKGROUND: Left ventricular non-compaction is
      characterized by a non-compacted myocardial layer in the left ventricle.
      Cardiovascular magnetic resonance images this layer with unprecedented quality,
      particularly in the ventricular apex, where echocardiography has inherent
      difficulties. METHODS: We analyzed magnetic resonance cine images, using the 17
      segment model in 45 healthy volunteers, 25 athletes, 39 patients with
      hypertrophic cardiomyopathy and 14 with dilated cardiomyopathy, 17 with
      hypertensive heart disease, and 30 with aortic stenosis, as well as images from 7
      patients previously diagnosed with LVNC whose diagnoses were supported by
      additional features. RESULTS: Areas of non-compaction were common and occurred
      more frequently in all groups studied in apical and lateral, rather than in basal
      or septal, segments. A NC/C ratio of >2.3 in diastole distinguished pathological
      non-compaction, with values for sensitivity, specificity, and positive and
      negative predictions of 86%, 99%, 75%, and 99%, respectively. CONCLUSIONS: Left
      ventricular non-compaction is diagnosed accurately with CMR using the NC/C ratio
      in diastole.

PMID- 15992643
TI  - Effects of aggressive versus conventional lipid-lowering therapy by simvastatin
      on human atherosclerotic lesions: a prospective, randomized, double-blind trial
      with high-resolution magnetic resonance imaging.
AB  - OBJECTIVES: This study sought to compare the effects of aggressive and
      conventional lipid lowering by two different dosages of the same statin on early
      human atherosclerotic lesions using serial noninvasive magnetic resonance imaging
      (MRI). BACKGROUND: Regression of atherosclerotic lesions by lipid-lowering
      therapy has been reported. METHODS: Using a double-blind design, newly diagnosed
      hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid
      atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n =
      22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57
      carotid plaques were detected and sequentially followed up by MRI every six
      months after lipid-lowering initiation. The primary MRI end point was change in
      vessel wall area (VWA) as a surrogate for atherosclerotic burden. RESULTS: Both
      statin doses reduced significantly total cholesterol (TC) and low-density
      lipoprotein cholesterol (LDL-C) versus baseline (p < 0.001). Total cholesterol
      decreased by 26% versus 33% and LDL-C by 36% versus 46% in the conventional (20
      mg) versus aggressive (80 mg) simvastatin groups, respectively. Although the
      simvastatin 80-mg group had significantly higher baseline TC and LDL-C levels,
      both groups reached similar absolute values after treatment. A significant
      reduction in VWA was already observed by 12 months. No difference on vascular
      effects was detected between the randomized doses. Post-hoc analysis showed that
      patients reaching mean on-treatment LDL-C < or = 100 mg/dl had larger decreases
      in plaque size. CONCLUSIONS: Effective and protracted lipid-lowering therapy with
      simvastatin is associated with a significant regression of atherosclerotic
      lesions. No difference in vessel wall changes was seen between high and
      conventional doses of simvastatin. Changes in vessel wall parameters are more
      related to LDL-C reduction rather than to the dose of statin.

PMID- 15992644
TI  - Papillary muscle dysfunction attenuates ischemic mitral regurgitation in patients
      with localized basal inferior left ventricular remodeling: insights from tissue
      Doppler strain imaging.
AB  - OBJECTIVES: The purpose of this research was to test whether papillary muscle
      (PM) dysfunction attenuates ischemic mitral regurgitation (MR) in patients with
      left ventricular (LV) remodeling of a similar location and extent. BACKGROUND:
      Papillary muscle dysfunction could attenuate tethering and MR because of PM
      elongation. However, variability in the associated LV remodeling, which
      exaggerates tethering, can influence the relationship between PM dysfunction and
      MR. METHODS: In 40 patients with a previous inferior myocardial infarction but
      without other lesions, the LV volume, sphericity, PM tethering distance, PM
      longitudinal systolic strain, and MR fraction were quantified by
      echocardiography. The patients were divided into two groups: group 1 with
      significant basal inferoposterior LV bulging but without advanced LV bulging
      involving other territories, therefore with a similar location and extent of LV
      remodeling, and group 2 without significant LV bulging. RESULTS: The medial PM
      tethering distance was significantly correlated with the %MR fraction (r2 = 0.64,
      p < 0.01), and multiple regression analysis identified an increase in the
      tethering distance as the only independent determinant of the MR fraction in all
      subjects and also in group 1. The PM longitudinal systolic strain had no
      significant relationships with MR fraction in all subjects with variable degrees
      of LV remodeling, but it had a significant inverse correlation with the MR
      fraction (r2 = 0.33, p < 0.01) in group 1 with LV remodeling of a similar
      location and extent, indicating that PM dysfunction is associated with less MR.
      CONCLUSIONS: Papillary muscle dysfunction, reducing its longitudinal contraction
      to induce leaflet tethering, attenuates ischemic MR in patients with basal
      inferior LV remodeling.

PMID- 15992645
TI  - Fish consumption among healthy adults is associated with decreased levels of
      inflammatory markers related to cardiovascular disease: the ATTICA study.
AB  - OBJECTIVES: The aim of this work was to investigate the association between fish
      consumption and levels of various inflammatory markers among adults without any
      evidence of cardiovascular disease. BACKGROUND: Fish consumption has been
      associated with reduced risk of coronary heart disease, but the mechanisms have
      not been well understood or appreciated. METHODS: The ATTICA study is a cross
      sectional survey that enrolled 1,514 men (age 18 to 87 years) and 1,528 women
      (age 18 to 89 years) from the Attica region, Greece. Of them, 5% of men and 3% of
      women were excluded due to a history of cardiovascular disease. Among others, C
      reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha,
      serum amyloid A (SAA), and white blood cells (WBC) were measured, and dietary
      habits (including fish consumption) were evaluated using a validated food
      frequency questionnaire. RESULTS: A total of 88% of men and 91% of women reported
      fish consumption at least once a month. Compared to non-fish consumers, those who
      consumed >300 g of fish per week had on average 33% lower CRP, 33% lower IL-6,
      21% lower TNF-alpha, 28% lower SAA levels, and 4% lower WBC counts (all p <
      0.05). Significant results were also observed when lower quantities (150 to 300
      g/week) of fish were consumed. All associations remained significant after
      various adjustments were made. CONCLUSIONS: Fish consumption was independently
      associated with lower inflammatory markers levels, among healthy adults. The
      strength and consistency of this finding has implications for public health and
      should be explored further.

PMID- 15992646
TI  - Erythropoietin induces neovascularization and improves cardiac function in rats
      with heart failure after myocardial infarction.
AB  - OBJECTIVES: We assessed the effects of erythropoietin (EPO) treatment in a rat
      model of post-myocardial infarction (MI) heart failure. BACKGROUND:
      Erythropoietin, traditionally known as a hematopoietic hormone, has been linked
      to neovascularization. Whereas administration of EPO acutely after MI reduces
      infarct size and improves cardiac function, its role in the failing heart is
      unknown. METHODS: Rats underwent coronary ligation or sham surgery. Rats with MI
      were randomly assigned to: untreated (MI), a single bolus of EPO immediately
      after MI induction (MI-EPO-early), EPO treatment immediately after MI and once
      every three weeks (MI-EPO-early+late), and EPO treatment starting three weeks
      after induction of MI, once every three weeks (MI-EPO-late). After nine weeks,
      hemodynamics, infarct size, myosin heavy chain (MHC) isoforms, myocyte
      hypertrophy, and capillary density were measured. RESULTS: Erythropoietin
      treatment started immediately after MI (MI-EPO-early and MI-EPO-early+late)
      resulted in a 23% to 30% reduction in infarct size (p < 0.01) and, accordingly,
      hemodynamic improvement. Erythropoietin treatment, started three weeks after MI
      (MI-EPO-late), did not affect infarct size, but resulted in an improved cardiac
      performance, reflected by a 34% reduction in left ventricular end-diastolic
      pressure (p < 0.01), and 46% decrease in atrial natriuretic peptide levels (p <
      0.05). The improved cardiac function was accompanied by an increased capillary
      density (p < 0.01), an increased capillary-to-myocyte ratio (p < 0.05), and a
      partial reversal of beta-MHC (p < 0.05) in all treated groups. CONCLUSIONS: In
      addition to its effect on infarct size reduction, EPO treatment improves cardiac
      function in a rat model of post-MI heart failure. This observation may be
      explained by neovascularization, associated with an increased alpha-MHC
      expression.

PMID- 15992647
TI  - Age-associated aortic stenosis in apolipoprotein E-deficient mice.
AB  - OBJECTIVES: The present study was designed to assess aortic valve morphology and
      function in mice of advanced age. We also evaluated the potential contribution of
      bone-marrow-derived cells to the pathogenesis of aortic stenosis. BACKGROUND: Age
      associated valvular degeneration is characterized by lipid accumulation, collagen
      deposition, and calcification containing smooth muscle-like cells and osteoblast
      like cells. Cellular and molecular factors that mediate these changes remain
      unknown. METHODS: We extensively examined the aortic valves of senile wild-type
      and apolipoprotein E (ApoE)-/- mice with echocardiography. The aortic valves were
      analyzed by immunohistochemistry and electron microscopy. The bone marrow of wild
      type and ApoE-/- mice was reconstituted with that of green fluorescent protein
      (GFP) or beta-galactosidase (LacZ) mice, which expressed GFP or LacZ
      ubiquitously. RESULTS: Transaortic flow velocity was correlated with age in wild
      type and ApoE-/- mice. The aortic valves of old ApoE-/- mice showed sclerosis
      that resembled the pathology of human aortic stenosis. A significant number of
      GFP-positive cells (10.7 +/- 4.1%) in the sclerotic valves of ApoE-/- mice
      expressed alpha-smooth muscle actin, whereas most of the GFP-positive cells were
      identified as endothelial cells or macrophages in wild-type mice. There were bone
      marrow-derived cells that were positive for osteoblast-related proteins near the
      sites of ectopic calcification. The sclerotic valves displayed frequent apoptotic
      cell death and chemokine expression. CONCLUSIONS: Senile ApoE-deficient mice
      display aortic valve sclerosis that is similar to that observed in humans. The
      sclerotic valves displayed frequent apoptotic cell death and chemokine
      expression. Smooth muscle-like cells observed in degenerative valves might
      derive, at least in part, from bone marrow.

PMID- 15992648
TI  - Diuretics and bone loss in rats with aldosteronism.
AB  - OBJECTIVES: We hypothesized that the increased urinary Ca2+ and Mg2+ excretion
      and bone loss that accompanies aldosteronism is aggravated with furosemide and is
      attenuated by spironolactone. BACKGROUND: Furosemide, a loop diuretic, is
      commonly used in patients with congestive heart failure (CHF), in which chronic,
      inappropriate (dietary Na+) elevations in plasma aldosterone (ALDO) and a
      catabolic state that includes bone wasting are expected. METHODS: In age- and
      gender-matched, untreated controls, four weeks of aldosterone/salt treatment
      (ALDO/salt, 0.75 microg/h + 1% NaCl/0.4% KCl in drinking water), four weeks of
      ALDO/salt + furosemide (40 mg/kg in prepared food), and four weeks of ALDO/salt +
      furosemide + spironolactone (200 mg/kg/day in divided doses by twice-daily
      gavage), we monitored: 24-h urinary Ca2+ and Mg2+ excretion; plasma-ionized
      [Ca2+]o and [Mg2+]o, K+, and parathyroid hormone (PTH); and bone mineral density
      (BMD) in the femur. RESULTS: The ALDO/salt increased (p < 0.05) urinary Ca2+ and
      Mg2+ excretion (4,969 +/- 1,078 and 3,856 +/- 440 microg/24 h, respectively)
      compared with controls (896 +/- 138 and 970 +/- 137 microg/24 h, respectively);
      furosemide co-treatment further increased (p < 0.05) urinary Ca2+ and Mg2+
      excretion (6,976 +/- 648 and 6,199 +/- 759 microg/24 h, respectively), whereas
      spironolactone co-treatment attenuated (p < 0.05) these incremental losses (4,003
      +/- 515 and 3,915 +/- 972 microg/24 h). Plasma [Ca2+]o was reduced (p < 0.05) at
      week 4 ALDO/salt + furosemide and was accompanied by hypokalemia (<3.4 mmol/l)
      that were rescued by spironolactone. Plasma PTH was increased (p < 0.05) compared
      with controls (30 +/- 4 vs. 11 +/- 3 pg/ml, respectively), whereas BMD was
      decreased (p < 0.05) with ALDO/salt and ALDO/salt + furosemide, but not with
      spironolactone co-treatment. CONCLUSIONS: In aldosteronism, hypercalciuria and
      hypermagnesuria and accompanying decrease in plasma-ionized [Ca2+]o and [Mg2+]o
      lead to hyperparathyroidism that accounts for bone wasting. Furosemide
      exaggerates these losses, whereas its combination with spironolactone attenuates
      these responses to prevent bone loss.

PMID- 15992649
TI  - Quantification of obstructive and nonobstructive coronary lesions by 64-slice
      computed tomography: a comparative study with quantitative coronary angiography
      and intravascular ultrasound.
AB  - OBJECTIVES: The aim of the present study was to determine the diagnostic accuracy
      of 64-slice computed tomography (CT) to identify and quantify atherosclerotic
      coronary lesions in comparison with catheter-based angiography and intravascular
      ultrasound (IVUS). BACKGROUND: Currently, the ability of multislice CT to
      quantify the degree of coronary artery stenosis and dimensions of coronary
      plaques has not been evaluated. METHODS: We included 59 patients scheduled for
      coronary angiography due to stable angina pectoris. A contrast-enhanced 64-slice
      CT (Senation 64, Siemens Medical Solutions, Forchheim, Germany) was performed
      before the invasive angiogram. In a subset of 18 patients, IVUS of 32 vessels was
      part of the catheterization procedure. RESULTS: In 55 of 59 patients, 64-slice CT
      enabled the visualization of the entire coronary tree with diagnostic image
      quality (American Heart Association 15-segment model). The overall correlation
      between the degree of stenosis detected by quantitative coronary angiography
      compared with 64-slice CT was r = 0.54. Sensitivity for the detection of stenosis
      <50%, stenosis >50%, and stenosis >75% was 79%, 73%, and 80%, respectively, and
      specificity was 97%. In comparison with IVUS, 46 of 55 (84%) lesions were
      identified correctly. The mean plaque areas and the percentage of vessel
      obstruction measured by IVUS and 64-slice CT were 8.1 mm2 versus 7.3 mm2 (p <
      0.03, r = 0.73) and 50.4% versus 41.1% (p < 0.001, r = 0.61), respectively.
      CONCLUSIONS: Contrast-enhanced 64-slice CT is a clinically robust modality that
      allows the identification of proximal coronary lesions with excellent accuracy.
      Measurements of plaque and lumen areas derived by CT correlated well with IVUS. A
      major limitation is the insufficient ability of CT to exactly quantify the degree
      of stenosis.

PMID- 15992650
TI  - Computed tomography of the coronary arteries: more than meets the (angiographic)
      eye.

PMID- 15992651
TI  - Coronary calcification, coronary disease risk factors, C-reactive protein, and
      atherosclerotic cardiovascular disease events: the St. Francis Heart Study.
AB  - OBJECTIVES: The purpose of this study was to determine the prognostic accuracy of
      electron beam computed tomographic (CT) scanning of the coronary arteries and the
      relationship of coronary calcification to standard coronary disease risk factors
      and C-reactive protein (CRP) in the prediction of atherosclerotic cardiovascular
      disease (ASCVD) events in apparently healthy middle-age persons. BACKGROUND: As a
      screening test for coronary artery disease (CAD), electron beam CT scanning
      remains controversial. METHODS: In a prospective, population-based study, 4,903
      asymptomatic persons age 50 to 70 years underwent electron beam CT scanning of
      the coronary arteries. RESULTS: At 4.3 years, follow-up was available in 4,613
      participants (94%), and 119 had sustained at least one ASCVD event. Subjects with
      ASCVD events had higher baseline coronary calcium scores (median [interquartile
      range], Agatston method) than those without events: 384 (127, 800) versus 10 (0,
      86) (p < 0.0001). For coronary calcium score threshold > or = 100 versus < 100,
      relative risk (95% confidence interval) was 9.6 (6.7 to 13.9) for all ASCVD
      events, 11.1 (7.3 to 16.7) for all CAD events, and 9.2 (4.9 to 17.3) for non
      fatal myocardial infarction and death. The coronary calcium score predicted CAD
      events independently of standard risk factors and CRP (p = 0.004), was superior
      to the Framingham risk index in the prediction of events (area under the receiver
      operating characteristic curve of 0.79 +/- 0.03 vs. 0.69 +/- 0.03, p = 0.0006),
      and enhanced stratification of those falling into the Framingham categories of
      low, intermediate, and high risk (p < 0.0001). CONCLUSIONS: The electron beam CT
      coronary calcium score predicts CAD events independent of standard risk factors,
      more accurately than standard risk factors and CRP, and refines Framingham risk
      stratification.

PMID- 15992652
TI  - Treatment of asymptomatic adults with elevated coronary calcium scores with
      atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized
      clinical trial.
AB  - OBJECTIVES: We sought to determine whether lipid-lowering therapy and
      antioxidants retard the progression of coronary calcification and prevent
      atherosclerotic cardiovascular disease (ASCVD) events. BACKGROUND: The electron
      beam computed tomography-derived coronary calcium score predicts coronary disease
      events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy
      slows progression of coronary calcification and prevents coronary artery disease
      events, but controlled, scientific demonstration of these effects is lacking.
      METHODS: We conducted a double-blind, placebo-controlled randomized clinical
      trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha
      tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic,
      apparently healthy men and women age 50 to 70 years with coronary calcium scores
      at or above the 80th percentile for age and gender. All study participants also
      received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. RESULTS:
      Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density
      lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by
      11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of
      coronary calcium score (Agatston method). Treatment also failed to significantly
      reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p =
      0.08). Event rates were related to baseline calcium score (pre-specified
      analysis) and may have been reduced in a subgroup of participants with baseline
      calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]).
      CONCLUSIONS: Treatment with alpha-tocopherol, vitamin C, and low doses of
      atorvastatin (20 mg once daily) did not affect the progression of coronary
      calcification. Treatment may have reduced ASCVD events, especially in subjects
      with calcium scores >400, but these effects did not achieve conventional levels
      of statistical significance.

PMID- 15992653
TI  - The changing face of cardiovascular risk.

PMID- 15992654
TI  - President's page: Reframing debate in patient care image.

PMID- 15992655
TI  - U-shaped relationship of blood glucose with adverse outcomes among patients with
      ST-segment elevation myocardial infarction.

PMID- 15992656
TI  - Frequency of cardiac troponin I mutations in families with hypertrophic
      cardiomyopathy in China.

PMID- 15992657
TI  - Impact of carvedilol before angiotensin-converting enzyme inhibitor therapy on
      cardiac function.

PMID- 15992659
TI  - Beta-blocker treatment before angiotensin-converting enzyme inhibitor therapy in
      newly diagnosed heart failure.

PMID- 15992660
TI  - Treatment order in managing systolic ventricular dysfunction.

PMID- 15992662
TI  - Integrating complementary medicine into cardiovascular medicine. A report of the
      American College of Cardiology Foundation Task Force on Clinical Expert Consensus
      Documents (Writing Committee to Develop an Expert Consensus Document on
      Complementary and Integrative Medicine).

PMID- 15992664
TI  - The endothelium in intensive care.
AB  - This article reviews the major role that the vascular endothelium plays in
      pathophysiological processes related to metabolism, vascular function, and blood
      coagulation. Normally an antithrombotic surface, inflammation activates
      endothelium to become a prothrombotic and pro-inflammatory interface that is
      critically involved in multi-organ failure in patients with severe systemic
      diseases including sepsis. Improving endothelial functions in sepsis is a major
      therapeutic challenge.

PMID- 15992665
TI  - Sepsis and coagulation.
AB  - The host response to infection is a highly complex yet well-orchestrated process
      that involves an elaborate array of soluble mediators and cells. Normally, the
      host response prevails in containing and eliminating the pathogenic threat. When
      excessive or sustained, however, the host response may "turn on its bearer" and
      lead to organ dysfunction. Severe sepsis is invariably associated with activation
      of primary and secondary hemostasis. This article describes sepsis-associated
      changes in coagulation, discusses the putative role for these changes in
      pathogenesis of the sepsis syndrome, and outlines current diagnostic and
      therapeutic strategies.

PMID- 15992666
TI  - Tissue factor pathway inhibitor and antithrombin trial results.
AB  - The endogenous plasma anticoagulant proteins tissue factor pathway inhibitor
      (TFPI) and antithrombin (AT) have both been extensively studied in large,
      multinational phase III clinical trials in patients with severe sepsis. The TFPI
      and AT trials failed to result in significant reductions in the 28-day, all-cause
      mortality rates in their respective study populations. However, there appear to
      be definable patient populations within each study that may have benefited from
      TFPI or AT. Drug-drug interactions and dosing issues were observed in both
      trials. The similarities and differences of each anticoagulant and the lessons
      learned from the recent phase III clinical trials are examined in this review.

PMID- 15992667
TI  - Disseminated intravascular coagulation: What's new?
AB  - Disseminated intravascular coagulation (DIC) is a syndrome characterized by a
      systemic activation of coagulation leading to the intravascular deposition of
      fibrin in the (micro) vasculature and the simultaneous consumption of coagulation
      factors and platelets. The occurrence of microvascular thrombosis as a
      consequence of DIC is underscored by pathological, experimental and clinical
      findings, demonstrating a link between DIC and organ dysfunction. Pathogenetic
      pathways that play a role in the development of DIC include tissue factor
      dependent activation of coagulation, defective physiological anticoagulant
      pathways (such as the antithrombin system and the protein C system), and impaired
      fibrinolysis, caused by elevated levels of plasminogen activator inhibitor type
      1. Novel therapeutic strategies are based on current insights into the
      pathogenesis of DIC, and include anticoagulant strategies (eg, directed at tissue
      factor) and strategies to restore physiological anticoagulant pathways (such as
      activated protein C concentrate).

PMID- 15992668
TI  - Does disseminated intravascular coagulation lead to multiple organ failure?
AB  - Microvascular dysfunction with its associated impaired regional oxygen transport
      and use is believed to be the final common pathway in the development of multiple
      organ failure. The precise mechanisms underlying this dysfunction, however, are
      uncertain. Activation of the coagulation system is a key feature in the
      pathogenesis of sepsis, but whether it is also the cause of multiple organ
      failure is unclear. This article discusses the evidence for and against a key
      role for disseminated intravascular coagulation in the pathogenesis of multiple
      organ failure.

PMID- 15992669
TI  - Transfusion-related acute lung injury and the ICU.
AB  - Transfusion-related acute lung injury (TRALI) has been the leading cause of
      transfusion-related deaths reported to the United States Food and Drug
      Administration for three consecutive years. Although traditionally TRALI has been
      viewed as having a one event pathogenesis (passive donor anti-leukocyte antibody
      interacting with a cognate antigen on the recipients leukocytes), emerging
      evidence suggests that TRALI is a multifactorial syndrome, and a true two-event
      subtype of ALI. Both recipient predisposition and biological response modifiers,
      generated during storage of cellular blood products, appear to play major
      pathogenetic roles. This review highlights recent advances in our knowledge of
      the pathophysiology of TRALI and recent progress towards a consensus definition
      of TRALI. It also guides the reader as to the recognition, investigation, and
      clinical management of TRALI.

PMID- 15992670
TI  - Venous thromboembolism in the ICU and reversal of bleeding on anticoagulants.
AB  - Venous thromboembolic disease is a very common complication in the ICU. This
      article reviews incidence, prevention, and therapy related to venous
      thromboembolism, including both deep venous thrombosis and pulmonary embolism.
      Special diagnostic and treatment considerations in the ICU setting are
      highlighted. The increased use of antithrombotic agents has led to an increased
      number of patients who experience bleeding complications on anticoagulant
      therapy. This review also addresses the methods of reversing various
      anticoagulants.

PMID- 15992671
TI  - Heparin, low molecular weight heparin, and heparin-induced thrombocytopenia in
      the ICU.
AB  - Thrombocytopenia is common in critically ill patients who receive heparin.
      However, heparin-induced thrombocytopenia (HIT) is a relatively uncommon
      explanation for thrombocytopenia in this patient population. This article
      describes clinical features of HIT and interpretation of laboratory tests for HIT
      antibodies from the perspective of the intensive care unit.

PMID- 15992672
TI  - Critical care clotting catastrophies.
AB  - Coagulation problems are very common in intensive care patients. It is important
      to recognize potential problems, perform a rapid assessment, and start therapy.
      The author reviews general clinical and laboratory approaches to diagnosis and
      treatment of the bleeding patient and to correction of coagulopathies. This
      review outlines a set of often catastrophic coagulation problems, which may
      present both thrombotic and bleeding challenges. These include heparin induced
      thrombocytopenia, thrombotic thrombocytopenic purpura, and disseminated
      intravascular coagulation.

PMID- 15992673
TI  - Hemostatic defects in end stage liver disease.
AB  - End stage liver disease results in a complex and variably severe failure of
      hemostasis that predisposes to abnormal bleeding. The diverse spectrum of
      hemostatic defects includes impaired synthesis of clotting factors, excessive
      fibrinolysis, disseminated intravascular coagulation, thrombocytopenia, and
      platelet dysfunction. Hemostasis screening tests are used to assess disease
      severity and monitor the response to therapy. Correction of hemostatic defects is
      required in patients who are actively bleeding or require invasive procedures.
      Fresh frozen plasma, cryoprecipitate, and platelet transfusion remain the
      mainstays of therapy until larger trials confirm the safety and efficacy of
      recombinant factor VIIa in this population.

PMID- 15992674
TI  - Bleeding in cardiac surgery: its prevention and treatment--an evidence-based
      review.
AB  - Expected and unexpected bleeding occur frequently in patients undergoing cardiac
      surgery. Bleeding after cardiac surgery can be broadly divided into two groups:
      surgical (unrecognized bleeding vessel, anastomosis, or other suture line) or
      nonsurgical bleeding (caused by coagulopathy). Factors influencing both surgical
      and nonsurgical bleeding can be further broken down into those occurring
      preoperatively and those that occur intraoperatively and postoperatively. A
      thorough understanding of these factors is necessary to reduce bleeding. This is
      a desirable clinical goal, because excessive bleeding is associated with adverse
      outcomes.

PMID- 15992675
TI  - Emerging off-label uses for recombinant activated factor VII: grading the
      evidence.
AB  - Recombinant activated factor VII (rFVIIa) is currently licensed in the United
      States for treatment of bleeding episodes in patients with deficiencies of factor
      VIII (FVIII) or IX (FIX) who are refractory to factor replacement because of
      circulating inhibitors. A 1999 report of its successful use to stop what was
      deemed to be lethal hemorrhage after an abdominal gunshot wound in a young
      soldier without pre-existing coagulopathy has prompted exploration of other uses
      for rFVIIa. The virtual explosion of proposed uses of rFVIIa raises issues not
      only regarding our understanding of the coagulation system, but also regarding
      its efficacy, cost-effectiveness, and safety.

PMID- 15992676
TI  - Beta-carotene breakdown products may impair mitochondrial functions--potential
      side effects of high-dose beta-carotene supplementation.
AB  - Beta-carotene (BC) and other carotenoids are mainly considered as belonging to
      the group of micronutrients. As they are contained in fruit and vegetables and
      thus part of human diet, a regular low-dose intake from natural sources is
      normally assured. In the last decade high-dose supplementation with synthetic
      carotenoids has been used successfully in the treatment of diseases believed to
      be associated with oxidative stress. However, in a few clinical studies harmful
      effects have been observed as well, e.g., a higher incidence of lung cancer after
      BC was given in high doses to smokers. Our studies aim at shedding light on the
      causal mechanisms of the known side effects that we have investigated.
      Possibilities of preventing them are discussed. Obviously, on certain conditions
      of high-dose carotenoid supplementation, both the antioxidant and prooxidant
      reactions may arise. Carotenoid breakdown products (CBP) including very reactive
      aldehydes and epoxides are formed during oxidative attack in the course of
      antioxidative action. Carotenoid breakdown products inhibit state 3 respiration
      of isolated rat liver mitochondria at concentrations between 0.5 and 20 microM.
      In vivo stimulated neutrophils might represent an important source for the
      generation of CBP, and the lung might be a critical organ in CBP formation. The
      inhibition of mitochondrial state 3 respiration by CBP is accompanied by a
      reduced content of protein sulfhydryl groups, decreasing glutathione levels and
      redox state, and also elevated accumulation of malondialdehyde. Changes in
      mitochondrial membrane potential favour functional deterioration of the adenine
      nucleotide translocator (ANT). The findings reflect a basic mechanism of the side
      effects of BC supplementation in circumstances of severe oxidative stress induced
      by CBP representing a class of lipid oxidation products. We are striving for safe
      conditions of carotenoid supplementation in order to protect patients in need of
      this kind of medical treatment from possible side effects, such as unwanted
      prooxidative reactions.

PMID- 15992677
TI  - Improved absorption of caseinophosphopeptide-bound iron: role of alkaline
      phosphatase.
AB  - Hydrolysis of proteins could lessen their inhibiting effect on the poor
      absorption of cow's milk iron (Fe), which is responsible for the high incidence
      of Fe deficiency worldwide. When bound to Fe, caseinophosphopeptides (CPP)
      derived from milk proteins resist luminal digestion, enhance Fe solubility and
      could improve its bioavailability; brush border enzyme alkaline phosphatase
      activity could influence iron absorption by releasing free Fe; this study
      assessed its role in the absorption of CPP-bound Fe. Rat duodenal loops were
      perfused with Fe gluconate or Fe bound to the CPP of beta casein [beta-CN (1
      25)], with or without the addition of an inhibitor of alkaline phosphatase,
      Na2WO4. The uptake of Fe-beta-CN (1-25) was greater than Fe gluconate. Na2WO4
      enhanced the uptake of Fe-beta-CN (1-25) and not of Fe gluconate. So the release
      of free, insoluble Fe, by alkaline phosphatase seems to be prevented by providing
      Fe in the Fe-beta-CN (1-25) complex form. Its good disappearance rate makes beta
      CN (1-25)-bound Fe a candidate for food fortification.

PMID- 15992679
TI  - Proceedings of the International Symposium on Vitamins as Regulators of Gene
      Expression: Biotin as a Model. December 3-4, 2004, Ixtapa, Mexico.

PMID- 15992678
TI  - Promotion of adenoma growth by dietary inulin is associated with increase in
      cyclin D1 and decrease in adhesion proteins in Min/+ mice mucosa.
AB  - We have earlier shown that dietary fructo-oligosaccharide inulin enhances adenoma
      growth in multiple intestinal neoplasia (Min/+) mice. To further explore inulin
      induced early biochemical changes in the normal-appearing mucosa, Min/+ mice were
      fed from the age of 5 weeks to the ages of 8 and 15 weeks a control diet or an
      inulin-enriched diet (10% w/w). In addition, the wild-type littermates were fed
      with the same diets until the age of 8 weeks, in order to determine whether
      similar changes happen both in the wild-type and Min/+ mice. The mucosa without
      adenomas was collected and fractionated to nuclear, cytosolic and membrane pools.
      The protein levels of beta-catenin, cyclin D1 and E-cadherin were determined by
      Western blotting at both time points, and immunohistochemical stainings were done
      for 8-week-old mice. The promotion of adenoma growth by inulin (week 15, 1.3-fold
      increase, P=.0004) was associated with accumulation of cytosolic and nuclear beta
      catenin, and increased amount of cytosolic cyclin D1 (1.5-fold increase, P=.003)
      in the normal-appearing mucosa of the Min/+ mice. Furthermore, inulin feeding
      reduced the membranous pools of beta-catenin and E-cadherin. Also in the wild
      type mice the drop in membranous beta-catenin was clear (P=.015), and, moreover,
      a subset of crypts had enhanced nuclear beta-catenin staining. These data
      indicate that dietary inulin can already activate in the normal-appearing mucosa
      beta-catenin signaling, which in the presence of Apc mutation induces adenoma
      growth and even in the wild-type mice direction of the changes is similar.

PMID- 15992680
TI  - The Escherichia coli biotin regulatory system: a transcriptional switch.
AB  - The ability of any organism to survive depends, in part, on mechanisms that
      enable it to modify its patterns of gene expression in response to extra- and
      intracellular signals. In the classical response mechanisms, a small molecule
      signal impinges on either an extra- or intracellular receptor, and through a
      series of events the signal is ultimately transmitted to transcription regulatory
      proteins. An alternative to this classical mechanism is provided by multi
      functional transcription factors. These proteins function directly in
      transcription as well as in at least one additional cellular process. An example
      of this class of proteins includes the dimerization cofactor of hepatocyte
      nuclear factor (DcoH), which serves as an enzyme involved in regeneration of the
      tetra-hydrobiopterin cofactor and as a factor that stabilizes the dimerization of
      the hepatocyte nuclear transcription factor (Mendel DB, Khavari PA, Conley PB,
      Graves MK, Hansen LP, Admon A, et al. Characterization of a cofactor that
      regulates dimerization of a mammalian homeodomain protein. Science 1991;254:1762
      7; Citron BA, Davis MD, Milstien S, Gutierrez J, Mendel DB, Crabtree GR. Identity
      of 4a-carbinolamine dehydratase, a component of the phenylalanine hydroxylation
      system, and DCoH, a transregulator of homeodomain proteins. Proc Natl Acad Sci U
      S A 1992;89:11891-4). Another example is the protein PutA, a redox enzyme
      involved in proline utilization and a regulator of transcription of the genes
      involved in proline utilization (Ostrovsky de Spicer P, Maloy S. Puta protein, a
      membrane-associated flavin dehydrogenase, acts as a redox-dependent
      transcriptional regulator. Proc Natl Acad Sci U S A 1993;90:4295-8). While
      several proteins of this class have been identified, their mechanisms of
      functional switching remain to be elucidated.

PMID- 15992681
TI  - Targeted and proximity-dependent promiscuous protein biotinylation by a mutant
      Escherichia coli biotin protein ligase.
AB  - A method for general protein biotinylation by enzymatic means has been developed.
      A mutant form (R118G) of the biotin protein ligase (BirA) of Escherichia coli is
      used and biotinylation is thought to proceed by chemical acylation of protein
      lysine side chains by biotinoyl-5'-AMP released from the mutant protein. Bovine
      serum albumin, chloramphenicol acetyltransferase, immunoglobulin chains and RNAse
      A as well as a large number of E. coli proteins have been biotinylated. The
      biotinylation reaction is proximity dependent in that the extent of biotinylation
      is much greater when the ligase is coupled to the acceptor protein than when the
      acceptor is free in solution. This is presumably due to rapid hydrolysis of the
      acylation agent, biotinoyl-5'-AMP. Therefore, when the mutant ligase is attached
      to one partner involved in a protein-protein interaction, it can be used to
      specifically tag the other partner with biotin, thereby permitting facile
      detection and recovery of the proteins by existing avidin/streptavidin
      technology.

PMID- 15992682
TI  - Biotin--a regulator of gene expression.
AB  - The role of biotin as the prosthetic group of the four biotin-dependent
      carboxylases in higher organisms is well recognized. Based on the roles of these
      carboxylases in metabolism, the requirement of biotin for cell viability, growth
      and differentiation was established. Biotin seems to have a role in cell
      functions other than as the prosthetic group of biotin enzymes. Biotin seems to
      influence processes such as the proliferation of the mesenchyme, spermatogenesis
      and song-bird vocalization. A direct effect of biotin, at the transcriptional
      level, has been shown for the key enzymes of glucose metabolism. Glucokinase, a
      key glycolytic enzyme, and phosphoenolpyruvate carboxykinase (PEPCK), a key
      gluconeogenic enzyme, are regulated in opposite directions by biotin in a manner
      similar to the action of insulin.

PMID- 15992683
TI  - Pharmacological effects of biotin.
AB  - In the last few decades, more vitamin-mediated effects have been discovered at
      the level of gene expression. Increasing knowledge on the molecular mechanisms of
      these vitamins has opened new perspectives that form a connection between
      nutritional signals and the development of new therapeutic agents. Besides its
      role as a carboxylase prosthetic group, biotin regulates gene expression and has
      a wide repertoire of effects on systemic processes. The vitamin regulates genes
      that are critical in the regulation of intermediary metabolism: Biotin has
      stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin
      receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases
      the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic
      enzyme that stimulates glucose production by the liver. The findings that biotin
      regulates the expression of genes that are critical in the regulation of
      intermediary metabolism are in agreement with several observations that indicate
      that biotin supply is involved in glucose and lipid homeostasis. Biotin
      deficiency has been linked to impaired glucose tolerance and decreased
      utilization of glucose. On the other hand, the diabetic state appears to be
      ameliorated by pharmacological doses of biotin. Likewise, pharmacological doses
      of biotin appear to decrease plasma lipid concentrations and modify lipid
      metabolism. The effects of biotin on carbohydrate metabolism and the lack of
      toxic effects of the vitamin at pharmacological doses suggest that biotin could
      be used in the development of new therapeutics in the treatment of hyperglycemia
      and hyperlipidemia, an area that we are actively investigating.

PMID- 15992684
TI  - Molecular genetics of biotin metabolism: old vitamin, new science.
AB  - Biotin is a water-soluble vitamin that participates as a cofactor in
      gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism.
      It functions as the carboxyl carrier for biotin-dependent carboxylases. Its
      covalent attachment to carboxylases is catalyzed by holocarboxylase synthetase.
      Our interest in biotin has been through the genetic disease, "biotin-responsive
      multiple carboxylase deficiency," caused by deficient activity of holocarboxylase
      synthetase. As part of these studies, we made the unexpected findings that the
      enzyme also targets to the nucleus and that it catalyzes the attachment of biotin
      to histones. We found that patients with holocarboxylase synthetase deficiency
      have a much reduced level of biotinylated histones, yet the importance of this
      process is unknown. The dual nature of biotin, as the carboxyl-carrier cofactor
      of carboxylases and as a ligand of unknown function attached to histones, is an
      enigma that suggests a much more involved role for biotin than anticipated. It
      may change our outlook on the optimal nutritional intake of biotin and its
      importance in biological processes such as development, cellular homeostasis and
      regulation.

PMID- 15992685
TI  - Biotin-dependent regulation of gene expression in human cells.
AB  - The role of biotin as cofactor of carboxylases and its importance in metabolic
      homeostasis are well known. In recent years, different researchers have suggested
      the participation of biotin as a regulator molecule in the control of gene
      expression. Biotin-dependent gene expression requires of the transformation of
      biotin into biotinyl-5'-AMP by holocarboxylase synthetase and the activation of
      soluble guanylate cyclase and a cGMP-dependent protein kinase. The regulatory
      role of biotin is responsible for the correct expression of enzymes involved in
      biotin utilization in human cells. We propose that this mechanism protects the
      brain from biotin deficiency.

PMID- 15992686
TI  - Marginal biotin deficiency is teratogenic in mice and perhaps humans: a review of
      biotin deficiency during human pregnancy and effects of biotin deficiency on gene
      expression and enzyme activities in mouse dam and fetus.
AB  - Recent studies of biotin status during pregnancy provide evidence that a marginal
      degree of biotin deficiency develops in a substantial proportion of women during
      normal pregnancy. Several lines of evidence suggest that although the degree of
      biotin deficiency is not severe enough to produce the classic cutaneous and
      behavioral manifestations of biotin deficiency, the deficiency is severe enough
      to produce metabolic derangements in women and may be teratogenic. In studies of
      mice, a similar degree of biotin deficiency induces characteristic fetal
      malformations at a high rate. Fetal hepatic biotin content and PCC activity
      decrease indicating that the fetuses also become biotin deficient. Fetal hepatic
      acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase and beta
      methylcrotonyl-CoA carboxylase abundances determined by Western blotting
      decreased more than the dam holocarboxylase abundances (10% of sufficient vs. 50%
      of sufficient); however, hepatic mRNA for the carboxylases and for HCS did not
      change significantly in either dams or fetuses. These observations suggest that
      maternal biotin deficiency results in a lack of adequate biotin to biotinylate
      apocarboxylases in the fetus despite the normal expression of genes coding for
      the apocarboxylases and holocarboxylase synthetase.

PMID- 15992687
TI  - Effects of biotin on growth and protein biotinylation in Saccharomyces
      cerevisiae.
AB  - In mammals, biotin, well known for its role as the cofactor of carboxylases, also
      controls the expression not only of proteins involved in this function, but also
      of a large number and variety of other different proteins. As a first step
      towards looking for a rationale for these phenomena, we intend to compare these
      regulatory functions of biotin between the rat and the much less evolutionized
      eukaryote, Saccharomyces cerevisiae. Thus far, we have measured growth in yeast
      cultured on different concentrations of biotin to choose the experimental
      conditions to be used (2, 200 and 2000 microM) and have found that a band
      corresponding to the biotinylated S. cerevisiae Arc1p protein appears at
      streptavidin Western blots at a biotin concentration above 2000 muM, its density
      increasing with higher biotin amounts. We will now study changes in yeast
      transcriptome with these varying concentrations and compare them with changes
      observed in the rat.

PMID- 15992688
TI  - Biotinidase: its role in biotinidase deficiency and biotin metabolism.
AB  - Renewed interest in biotinidase, the enzyme responsible for recycling the vitamin
      biotin, initially came from the discovery of biotinidase deficiency in 1982.
      Since then, the elucidation of other activities of the enzyme, alternative
      splicing of the biotinidase gene and differential subcellular localization of the
      enzyme have prompted speculation and investigations of its other possible
      functions. The results of these studies have implicated biotinidase in aspects of
      biotin metabolism, specifically the biotinylation of various proteins, such as
      histones. Biotinidase may have an important regulatory role(s) in chromatin/DNA
      function.

PMID- 15992689
TI  - Biological functions of biotinylated histones.
AB  - Histones H1, H2A, H2B, H3 and H4 are DNA-binding proteins that mediate the
      folding of DNA into chromatin. Various posttranslational modifications of
      histones regulate processes such as transcription, replication and repair of DNA.
      Recently, a novel posttranslational modification has been identified: covalent
      binding of the vitamin biotin to lysine residues in histones, mediated by
      biotinidase and holocarboxylase synthetase. Here we describe a novel peptide
      based technique, which was used to identify eight distinct biotinylation sites in
      histones H2A, H3 and H4. Biotinylation site-specific antibodies were generated to
      investigate biological functions of histone biotinylation. Evidence was provided
      that biotinylation of histones plays a role in cell proliferation, gene silencing
      and cellular response to DNA damage.

PMID- 15992690
TI  - Keynote comment: Dumbing down of complementary medicine.

PMID- 15992691
TI  - Alcohol and cancer: benefits in addition to risks?

PMID- 15992692
TI  - MAPK pathway activation in colorectal cancer: a therapeutic opportunity for GRP
      receptor antagonists.

PMID- 15992693
TI  - Chinese government urged to tame cancer threat.

PMID- 15992694
TI  - Adjuvant regional chemotherapy and systemic chemotherapy versus systemic
      chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre
      randomised controlled phase III trial.
AB  - BACKGROUND: Systemic adjuvant chemotherapy can improve overall survival and
      reduce the incidence of distant metastases for patients with advanced colon
      cancer. This study aimed to investigate whether regional chemotherapy (given by
      intraperitoneal or intraportal methods) combined with systemic chemotherapy was
      more effective than was systemic chemotherapy alone in terms of survival and
      recurrence for patients with stage II-III colorectal cancer. The study also
      compared systemic chemotherapy with fluorouracil and folinic acid with that of
      fluorouracil and levamisole. METHODS: During surgery, 753 patients with stage II
      III colorectal cancer were randomly assigned to systemic chemotherapy alone (379
      with fluorouracil and folinic acid, and 374 with fluorouracil and levamisole),
      and 748 to postoperative regional chemotherapy with fluorouracil followed by
      systemic chemotherapy with fluorouracil and folinic acid (n=368) or with
      fluorouracil and levamisole (n=380). Regional chemotherapy was given
      intraperitoneally (n=415) or intraportally (n=235) according to institution. The
      primary endpoint was 5-year overall survival. Secondary endpoints were 5-year
      disease-free survival and toxic effects. Analyses were by intention to treat.
      FINDINGS: Median follow-up was 6.8 years (range 0.0-10.1). 5-year overall
      survival was 72.3% (95% CI 69.0-75.6) for patients assigned regional and systemic
      chemotherapy, compared with 72.0% (68.7-75.3) for those assigned systemic
      chemotherapy alone (hazard ratio [HR] 0.97 [0.81-1.15], p=0.69). 5-year overall
      survival for all patients assigned fluorouracil and levamisole was 72.0% (68.7
      75.2) compared with 72.3% (69.0-75.6) for all those assigned fluorouracil and
      folinic acid (HR 0.98 [0.82-1.17], p=0.81). The hazard ratios for 5-year disease
      free survival were 0.94 (0.80-1.10) for regional versus non-regional treatment,
      and 0.92 (0.79-1.08) for all fluorouracil and levamisole versus fluorouracil and
      folinic acid. Grade 3-4 toxic effects were low in all groups. INTERPRETATION:
      Fluorouracil-based regional chemotherapy adds no further benefit to that obtained
      with systemic chemotherapy alone in patients with advanced colorectal cancer.

PMID- 15992695
TI  - Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis.
AB  - BACKGROUND: Previous epidemiological studies of the relation between alcohol
      consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent,
      probably because of small sample sizes of individual studies that result from
      stratification by NHL subtype and type of alcoholic beverage. We aimed to assess
      the role of alcohol consumption in NHL with sufficient sample size to analyse by
      both type of alcoholic beverage and disease subtype. METHODS: We obtained
      original data from nine case-control studies from the USA, UK, Sweden, and Italy
      in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a
      pooled study population of 15 175 individuals (6492 cases and 8683 controls). We
      derived odds ratios (OR) and 95% CI from unconditional logistic regression
      models, controlling for study centre and other confounding factors. Heterogeneity
      between studies was assessed by comparison of results from joint fixed-effects
      logistic regression and two-stage random-effects logistic regression, and by
      calculation of Wald chi(2) statistics. FINDINGS: People who drank alcohol had a
      lower risk of NHL than did non-drinkers (OR 0.83 [95% CI 0.76-0.89]). Compared
      with non-drinkers, risk estimates were lower for current drinkers than for former
      drinkers (0.73 [0.64-0.84] vs 0.95 [0.80-1.14]), but risk did not decrease with
      increasing alcohol consumption. The protective effect of alcohol did not vary by
      beverage type, but did change with NHL subtype. The lowest risk estimates were
      recorded for Burkitt's lymphoma (0.51 [0.33-0.77]). INTERPRETATION: People who
      drink alcoholic beverages might have a lower risk of NHL than those who do not,
      and this risk might vary by NHL subtype. Further study designs are needed to
      determine whether confounding lifestyle factors or immunomodulatory effects of
      alcohol explain this association.

PMID- 15992696
TI  - Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of
      a randomised trial.
AB  - BACKGROUND: The safety and short-term benefits of laparoscopic colectomy for
      cancer remain debatable. The multicentre COLOR (COlon cancer Laparoscopic or Open
      Resection) trial was done to assess the safety and benefit of laparoscopic
      resection compared with open resection for curative treatment of patients with
      cancer of the right or left colon. METHODS: 627 patients were randomly assigned
      to laparoscopic surgery and 621 patients to open surgery. The primary endpoint
      was cancer-free survival 3 years after surgery. Secondary outcomes were short
      term morbidity and mortality, number of positive resection margins, local
      recurrence, port-site or wound-site recurrence, metastasis, overall survival, and
      blood loss during surgery. Analysis was by intention to treat. Here, clinical
      characteristics, operative findings, and postoperative outcome are reported.
      FINDINGS: Patients assigned laparoscopic resection had less blood loss compared
      with those assigned open resection (median 100 mL [range 0-2700] vs 175 mL [0
      2000], p<0.0001), although laparoscopic surgery lasted 30 min longer than did
      open surgery (p<0.0001). Conversion to open surgery was needed for 91 (17%)
      patients undergoing the laparoscopic procedure. Radicality of resection as
      assessed by number of removed lymph nodes and length of resected oral and aboral
      bowel did not differ between groups. Laparoscopic colectomy was associated with
      earlier recovery of bowel function (p<0.0001), need for fewer analgesics, and
      with a shorter hospital stay (p<0.0001) compared with open colectomy. Morbidity
      and mortality 28 days after colectomy did not differ between groups.
      INTERPRETATION: Laparoscopic surgery can be used for safe and radical resection
      of cancer in the right, left, and sigmoid colon.

PMID- 15992697
TI  - Hernias and Ewing's sarcoma family of tumours: a pooled analysis and meta
      analysis.
AB  - BACKGROUND: Ewing's sarcoma family of tumours has been associated with a history
      of hernia and with a parental occupation of farming. However, the causes of these
      tumours remain unknown. We therefore aimed to investigate the association between
      hernia and Ewing's sarcoma family of tumours. METHODS: We did a pooled analysis
      of two case-control studies and a meta-analysis of three case-control studies of
      Ewing's sarcoma family of tumours that had adequate information on history of
      hernia. The primary endpoint was development of a tumour from the Ewing's sarcoma
      family. 138 patients with such a tumour and 574 controls were included in the
      pooled analysis, and 357 patients with these tumours and 745 controls were
      included in the meta-analysis. Risk was assessed by an odds ratio (OR) and 95% CI
      by use of multivariate analysis with unconditional logistic regression for the
      pooled analysis and random effects model for the meta-analysis. FINDINGS: Pooled
      analysis showed that children with Ewing's sarcoma family of tumours were more
      likely to have had an umbilical hernia than were controls (odds ratio [OR] 3.3
      [95% CI 1.3-8.0]). Meta-analysis showed that children with Ewing's sarcoma family
      of tumours were more likely to have had a hernia (3.2 [1.9-5.7]). INTERPRETATION:
      Ewing's sarcoma family of tumours and hernias (particularly inguinal hernias)
      have common embryological pathways of neuroectodermal origin, and environmental
      factors, such as farming, might link the two entities.

PMID- 15992698
TI  - Cutaneous side-effects of kinase inhibitors and blocking antibodies.
AB  - Although kinase inhibitors raise hope for people with cancer, patients and their
      clinicians are commonly confronted with the cutaneous side-effects that are
      associated with the use of these drugs. This review is the result of
      collaborations between dermatologists, medical oncologists, and pathologists, and
      discusses the cutaneous side-effects seen after treatment with the inhibitors of
      epidermal-growth-factor receptor (EGFR), imatinib, sorafenib, and sunitinib. Some
      of the side-effects caused by these agents are very distressing, partly because
      they are chronic owing to the long duration of treatment. Therefore, patients
      need early and appropriate dermatological management. Moreover, several studies
      have reported a link between the antitumour efficacy of EGFR inhibitors and
      cutaneous side-effects. Elucidation of this connection could lead to the
      identification of crucial predictive factors for tumour response.

PMID- 15992699
TI  - Clinical phenotypes and molecular genetic mechanisms of Carney complex.
AB  - Carney complex is a familial multiple neoplasia disorder with characteristic
      features such as cardiac and cutaneous myxomas and spotty pigmentation of the
      skin. Clinical genetic analyses have shown that Carney complex is transmitted in
      an autosomal dominant way and can present with a wide array of other tumours,
      such as psammomatous melanotic schwannoma, testicular Sertoli-cell tumours, and
      pituitary adenomas. Molecular genetic studies show that mutations in the PRKAR1A
      gene, encoding the R1alpha regulatory subunit of cyclic-AMP-dependent protein
      kinase A, are the cause of Carney complex in most patients. Investigation of
      genetically engineered animal models confirms the role of PRKAR1A as a tumour
      suppressor and has begun to elaborate mechanisms underlying tumorigenesis in this
      disorder. Further genetic studies in human beings have highlighted novel variant
      phenotypes, such as congenital contractures, which are potentially associated
      with Carney complex, and have identified alternative genetic pathways to cardiac
      tumorigenesis, including mutation of the MYH8 gene that encodes perinatal myosin.

PMID- 15992700
TI  - Radiotherapy of localised intracranial germinoma: time to sever historical ties?
AB  - The optimum management of localised intracranial germinoma remains controversial.
      Cure rates for this rare CNS tumour, which arises mainly in adolescents, exceed
      90% at 10 years, and limitation of treatment-related late morbidity is therefore
      essential. Craniospinal radiotherapy plus boost is perceived to be the gold
      standard treatment, but there have been suggestions that reduced-volume
      radiotherapy could be adequate for cure. We reviewed publications since 1988 to
      compare patterns of disease relapse and cure rates after craniospinal
      radiotherapy, reduced-volume irradiation alone (i.e., whole-brain or whole
      ventricular irradiation followed by a boost), and focal or localised irradiation
      alone. The recurrence rate after whole-brain or whole-ventricular radiotherapy
      plus boost was 7.6% compared with 3.8% after craniospinal radiotherapy, with no
      predilection for isolated spinal relapses (2.9% vs 1.2%). We challenge the
      consensus that craniospinal radiotherapy is the best treatment for localised
      germinomas and conclude that reduced-volume radiotherapy plus boost should
      replace craniospinal radiotherapy when a radiotherapy-only approach is used.

PMID- 15992701
TI  - New insights on cell death from radiation exposure.
AB  - Ionising radiation has been an important part of cancer treatment for almost a
      century, being used in external-beam radiotherapy, brachytherapy, and targeted
      radionuclide therapy. At the molecular and cellular level, cell killing has been
      attributed to deposition of energy from the radiation in the DNA within the
      nucleus, with production of DNA double-strand breaks playing a central part.
      However, this DNA-centric model has been questioned because cell-death pathways,
      in which direct relations between cell killing and DNA damage diverge, have been
      reported. These pathways include membrane-dependent signalling pathways and
      bystander responses (when cells respond not to direct radiation exposure but to
      the irradiation of their neighbouring cells). New insights into mechanisms of
      these responses coupled with technological advances in targeting of cells in
      experimental systems with microbeams have led to a reassessment of the model of
      how cells are killed by ionising radiation. This review provides an update on
      these mechanisms.

PMID- 15992702
TI  - Is total thyroidectomy the best possible surgical management for well
      differentiated thyroid cancer?

PMID- 15992703
TI  - Proton radiotherapy for Hodgkin's disease in the sacrum.

PMID- 15992704
TI  - Response of carcinoma of unknown primary site affecting bone to thalidomide.

PMID- 15992705
TI  - Clivus chordoma associated with a pontine arachnoid cyst.

PMID- 15992706
TI  - The use of Tissue Doppler Imaging for the assessment of changes in myocardial
      structure and function in inherited cardiomyopathies.
AB  - Although there is still a long way to go, our understanding of the genetic basis
      of cardiomyopathies--dilated or hypertrophic--has significantly improved over the
      past decade. This new and intriguing era of cardiogenetics has already answered
      some important questions concerning the pathophysiology of these disorders, but
      it has also raised some new questions: how do we define "presymptomatic" mutation
      carriers? Should we treat them? Do we have any diagnostic tools to identify the
      presymptomatic subjects in those families where the underlying mutation has not
      been identified yet? To address at least part of these questions, there is a
      clear need for screening techniques in the early stage of the disease which have
      to be sensitive and non-invasive. In recent years Tissue Doppler Imaging (TDI)
      has emerged as a well suited technique for these purposes and several interesting
      papers on this issue have been published. This paper reviews the findings from
      TDI in several forms of inherited cardiomyopathy. Although the implementation of
      this technique in everyday clinical practice still requires some refinement, the
      results from these studies are encouraging and TDI is likely to be complementary
      to other established screening tools such as ECG and conventional
      echocardiography.

PMID- 15992707
TI  - Noninvasive assessment of coronary flow velocity reserve in left anterior
      descending artery adds diagnostic value to both clinical variables and dobutamine
      echocardiography: a study based on clinical practice.
AB  - AIMS: Our objective was to evaluate, in clinical practice, whether noninvasive
      assessment of coronary flow velocity reserve in left anterior coronary artery
      adds diagnostic information to both clinical variables and wall motion
      abnormalities derived from dobutamine stress echocardiography. METHODS AND
      RESULTS: We studied 130 patients who were scheduled for coronary angiography
      after undergoing dobutamine stress echocardiography. The same day, flow in left
      anterior descending artery was detected by transthoracic Doppler
      echocardiography. A Doppler signal of left anterior descending artery was
      detected in 110 patients (85%). We identified significant left anterior
      descending artery stenosis (>50% diameter stenosis) in 42 patients. Sensitivity
      and specificity of abnormal coronary flow velocity reserve (<2) to detect left
      anterior descending artery stenosis were 86% and 57%, respectively. Wall motion
      abnormalities had a sensitivity and specificity of 52% and 82%. After forcing the
      clinical and dobutamine stress echo variables into a regression model with three
      modeling steps, an abnormal coronary flow velocity reserve provided incremental
      information in predicting significant left anterior descending artery stenosis.
      CONCLUSION: An abnormal coronary flow velocity reserve by transthoracic Doppler
      echocardiography adds diagnostic value to both clinical data and variables
      derived from dobutamine stress echo to detect significant left anterior
      descending artery stenosis.

PMID- 15992708
TI  - The echocardiographic assessment of donor heart function prior to cardiac
      transplantation.

PMID- 15992709
TI  - The use of isovolumic contraction velocity to determine right ventricular state
      of contractility and filling pressures A pulsed Doppler tissue imaging study.
AB  - AIMS: Echocardiographic techniques have not so far been able to provide a good
      estimation of myocardial contractility in humans. Myocardial motion during the
      isovolumic contraction phase, measured by Doppler tissue imaging, has only
      recently in experimental models been shown to describe myocardial contractility.
      The aim of the present clinical study was to investigate the relationship between
      right ventricular isovolumic contraction velocity and right ventricular state of
      contractility. METHODS AND RESULTS: Doppler tissue imaging and cardiac
      catheterization were performed simultaneously in 26 consecutive patients with
      different cardiac diseases (18 males, mean age 52 +/- 12, range 23-75 years).
      Peak isovolumic contraction velocity was measured using Doppler tissue imaging at
      2 levels of the right ventricular free wall. During cardiac catheterization, the
      first derivative of right ventricular pressure related to the pulmonary artery
      peak pressure (dP/dt/P(max)) was measured. Furthermore, right ventricular end
      diastolic pressure, right atrial mean pressure, pulmonary artery systolic
      pressure, and pulmonary artery resistance, were also measured. A significant
      relationship was found between isovolumic contraction velocity and dP/dt/P(max)
      (r = 0.59, p < 0.01). This relationship was strengthened after excluding patients
      with elevated right atrial pressures (r = 0.77, p < 0.001). Furthermore, a
      correlation was also found between basal and mid cavity isovolumic contraction
      velocity and right ventricular end diastolic pressure (r = -0.47, r = -0.49, p <
      0.05) as well as right atrial mean pressure (r = -0.63, r = -0.55, p < 0.01).
      CONCLUSION: Isovolumic contraction velocity is a reproducible and easily
      obtainable non-invasive parameter which correlates with invasive measurements of
      right ventricular state of contractility and right ventricular filling pressures.

PMID- 15992710
TI  - Prognostic value of supine bicycle exercise stress echocardiography in patients
      with known or suspected coronary artery disease.
AB  - AIMS: To assess the prognostic significance of supine bicycle exercise stress
      echocardiography (ESE) for cardiac events, and the ESE additional role compared
      to other traditional clinical and echo variables, in patients with proven or
      suspected coronary artery disease (CAD). METHODS AND RESULTS: Clinical status and
      long-term outcome were assessed in 607 patients, for a mean period of 49.9 +/-
      12.5 months. ESE was performed for the diagnosis of suspected CAD in 267
      patients, and for the risk stratification in 340 patients. At baseline, the mean
      value of WMSI was 1.22 +/- 0.36, and the mean left ventricular ejection fraction
      was 58.2 +/- 10.9%. The ESE was positive for ischemia in 210 patients (34.9%),
      while the ECG was suggestive for ischemia in 157 patients. At peak effort, the
      mean WMSI was 1.38 +/- 0.46. Low work load was achieved by 158 patients (26.1%).
      During the follow-up period there were 222 events, including 48 cardiac deaths
      and 34 acute non-fatal myocardial infarction. By multivariable model, cigarette
      smoking, peak WMSI, positive ESE for ischemia and low work load were the only
      independent predictors of cardiac death. The cumulative 5-year mean survival rate
      according to ESE response was 95.9% in patients with negative ESE, and 81.7% in
      positive ESE (p < 0.00001). CONCLUSIONS: In patients with known or suspected CAD
      able to perform a physical stress, bicycle ESE is able to stratify patients at
      higher risk of cardiac events. The final report of an ESE performed for
      prognostic purpose should include both the assessment of induced dyssinergy and
      the evaluation of indexes of the extent and the severity of myocardial ischemia.

PMID- 15992711
TI  - Intraoperative echocardiographic assessment of the severe isolated ostial
      stenosis of left main coronary artery before and after surgical patch
      angioplasty.
AB  - Isolated critical ostial stenosis of left main coronary artery is currently
      treated by conventional bypass surgery. Surgical patch angioplasty in an
      alternative surgical approach. Transesophageal echocardiography enables
      visualization of proximal branches of left and right coronary artery. The report
      describes intraoperative echocardiographic assessment of surgical left main
      coronary artery angioplasty.

PMID- 15992712
TI  - An elusive cystic mass in right atrium.

PMID- 15992713
TI  - Serial pressure gradients across a thoracic coarctation of the aorta during
      pregnancy.
AB  - Case of maternal aortic coarctation distal to the left subclavian artery followed
      throughout a successful pregnancy with serial echocardiography. We demonstrate
      changes in pressure gradients across the defect which may have management
      implications in similar pregnancies.

PMID- 15992714
TI  - Mitral paraprosthetic leak diagnosed by transesophageal echocardiography through
      nasal way.
AB  - Paraprosthetic leaks are a postoperatively complication recurring with a
      frequency from 15 to 30%, and mostly in the mitral than in the aortic position.
      Transthoracic echocardiography can suspect prosthesis valve dysfunction, but for
      both diagnosis and evaluation of the paraprosthetic dysfunction severity,
      transesophageal study is required. In this report a mitral paraprosthetic
      dehiscence was diagnosed using a miniaturized, 10 F, monoplane probe inserted
      through nasal way. This technique, that do not require topical and general
      anesthesia, appears to be well tolerated providing an accurate and more
      comfortable examination.

PMID- 15992715
TI  - Recurrent multiple cardiac hydatidosis.
AB  - Cardiac hydatid cyst is an uncommon disease. We report on a woman admitted to our
      clinic with chest pain and palpitations. The ECG showed anterior ischemia, and
      coronary anatomy was normal. The diagnosis was: multiple cardiac hydatid cysts,
      for which she had undergone surgery 4 years earlier for a 5 x 5 hydatid cyst and
      treated with albendazole. Despite this, there was a recurrence of multiple cysts.
      Recurrence of intracavitary hydatid cyst is rare, and surgical treatment of
      multiple, small cysts remains controversial.

PMID- 15992716
TI  - Underestimation of severity of mitral regurgitation with varying hemodynamics.
AB  - Transesophageal echocardiography (TEE) is a valuable technique to assess mitral
      valve anatomy and the mechanism of mitral regurgitation (MR). We present the case
      of a 35-year-old woman with severe MR due to restrictive motion of the posterior
      mitral leaflet, who was referred for mitral annuloplasty. Under physiologic
      circumstances, a severe (grade 3+) MR was present, whereas in the operating room
      during general anesthesia, the MR had disappeared almost completely. The
      downgrading of MR due to general anesthesia and the associated mechanisms of this
      phenomenon are discussed in this case.

PMID- 15992717
TI  - Cardiac hypertrophy and how it may break an athlete's heart--the Cypriot case.
AB  - AIMS: This is a case report of an athlete whose professional football career was
      transiently terminated because of the presumed diagnosis of hypertrophic
      cardiomyopathy. METHODS AND RESULTS: The diagnosis was based on
      electrocardiographic repolarisation changes. The ECGs, treadmill exercise tests
      (Bruce protocol) and echo examinations at the time of his active training and
      several years after termination of his professional career are discussed. No
      hypertrophic cardiomyopathy was documented by ultrasound examination.
      CONCLUSIONS: The distinction between physiological athlete's heart and
      pathological conditions has critical implications for professional athletes.
      Criteria and guidelines for screening of athletes in competitive sports are
      recommended.

PMID- 15992718
TI  - Aortic dissection with diastolic prolapse of intimal flap into left ventricle.
AB  - Ascending aortic dissection is often a catastrophic condition. Dissection into
      the commissures or into an aortic valve leaflet may lead to leaflet avulsion and
      valvular insufficiency due to a flail valve. We present an image report
      describing an important and life-threatening complication due to the movement of
      a partially dehisced intimal aortic flap into the left ventricle causing aortic
      valve insufficiency in a patient with acute dissection of the ascending aorta.

PMID- 15992719
TI  - Unpredictable implantable cardioverter-defibrillator pulse generator failure due
      to electrical overstress causing sudden death in a young high-risk patient with
      hypertrophic cardiomyopathy.

PMID- 15992720
TI  - Implantable cardioverter-defibrillator product reliability: recalling lessons
      from a tragic case.

PMID- 15992722
TI  - Mechanical termination of ventricular tachycardia: conducting bundles bumped or
      blocked?

PMID- 15992721
TI  - Mechanical interruption of postinfarction ventricular tachycardia as a guide for
      catheter ablation.
AB  - BACKGROUND: Mechanical trauma has been described as a helpful guide for ablation
      of atrial tachycardias and accessory pathways. In postinfarction ventricular
      tachycardia (VT), the reentrant circuit is partly endocardial and therefore may
      be susceptible to catheter trauma. OBJECTIVES: The purpose of this study was to
      determine the prevalence and significance of VT termination resulting from
      catheter trauma. METHODS: A consecutive series of 39 patients (mean age 68 +/- 7
      years, ejection fraction 0.25 +/- 0.02) underwent left ventricular mapping for
      postinfarction VT. Mapping was performed during 62 hemodynamically tolerated VTs
      (mean cycle length 451 +/- 88 ms). Only hemodynamically tolerated VTs that did
      not terminate spontaneously and VTs that were reproducibly inducible were
      included in the study. VT termination was considered mechanical only if it was
      not caused by a premature depolarization. RESULTS: In 13 of 62 VTs (21%) in 8 of
      39 patients (21%), either VT terminated during catheter placement at a particular
      site (n = 7) or a previously reproducibly inducible VT became no longer inducible
      with the mapping catheter located at a particular site (n = 6). The stimulus-QRS
      interval was significantly shorter at sites where mechanical trauma affected the
      reentrant circuit compared with sites having concealed entrainment (102 +/- 56 ms
      vs 253 +/- 134 ms, P = .003). At the site that was susceptible to mechanical
      trauma, the pace map was identical or highly similar in 13 of 13 VTs. After
      radiofrequency ablation at these sites, the targeted VTs were no longer
      inducible. No patient had recurrence of the targeted VT during a mean follow-up
      of 15 +/- 11 months. CONCLUSIONS: Catheter contact at a critical endocardial site
      can interrupt postinfarction VT or prevent its induction. Radiofrequency ablation
      at sites of mechanical termination of VT has a high probability of success.

PMID- 15992723
TI  - Topographic analysis of the coronary sinus and major cardiac veins by computed
      tomography.
AB  - BACKGROUND: The coronary sinus (CS) and its branches may play a role in the
      genesis of various arrhythmias. Applications of radiofrequency energy within the
      CS may be necessary. Atrio-esophageal fistula has been recognized as a
      complication of ablation along the posterior left atrial wall. OBJECTIVES: The
      purpose of this study was to describe the in vivo topographic anatomy of the CS,
      esophagus, and coronary arteries using computed tomography (CT). METHODS: Helical
      contrast CT of the heart with three-dimensional and endoscopic reconstructions
      was performed in 50 patients (28 men and 22 women; mean age 54 +/- 10 years). The
      images were reformatted to determine the relationships among the CS, adjacent
      blood vessels, and esophagus and to determine the nature and thickness of
      surrounding tissue layers. RESULTS: Mean CS ostium diameter was 12 +/- 4 mm, and
      mean thickness of the periosteal fat layer was 3 +/- 2 mm. In 40 of the 50
      patients (80%), the esophagus was adjacent to the CS, starting 24 +/- 9 mm from
      the ostium, and remained in contact for a mean length of 7 +/- 5 mm. Mean
      thickness of the fat layer between the esophagus and CS was 1 +/- 1 mm, and mean
      thickness of the anterior wall of the esophagus was 3 +/- 2 mm. In 10 patients
      (20%), there was no contact between the esophagus and CS. In 40 patients (80%),
      the right coronary artery was less than 5 mm from the CS (minimum distance 1 +/-
      1 mm) over a mean length of 17 +/- 11 mm. In all patients, the circumflex artery
      was less than 5 mm from the CS (minimum distance 1 +/- 0.4 mm) over a mean length
      of 16 +/- 9 mm in patients with right-dominant coronary circulation and over a
      mean length of 86 +/- 11 mm in patients with left-dominant coronary circulation.
      CONCLUSION: The CS often lies very close to the esophagus and coronary arteries.
      During radiofrequency energy ablation in the CS, caution should be exercised to
      prevent injury to surrounding structures.

PMID- 15992724
TI  - Prospective trial of electroanatomically guided, irrigated catheter ablation of
      atrial tachycardia in patients with congenital heart disease.
AB  - BACKGROUND: Ablation success rates reported for atrial tachycardia (AT) patients
      with congenital heart disease (CHD) is lower than the rates reported for other
      varieties of supraventricular tachycardia. Retrospective studies suggest these
      rates might be increased by the use of irrigated radiofrequency (RF) ablation.
      OBJECTIVES: The purpose of this study was to determine whether irrigated RF
      ablation increases ablation success rates in patients with CHD and AT. METHODS:
      Patients were studied in a prospective, randomized, nonblinded manner. The
      operator was limited to use of randomized therapy (standard or irrigated
      ablation) for the first 6 minutes of RF application to each targeted arrhythmia.
      Lesion characteristics were recorded, and acute ablation success was ascertained.
      Structured clinical follow-up was performed over a 6-month period. RESULTS: Forty
      seven ATs were targeted in 26 patients; 72% of these ATs were ablated. Within the
      6-minute randomization period, no difference in success rates of standard and
      irrigated catheters was noted. However, crossover from standard to irrigated
      ablation more likely was successful than vice versa (irrigated: 8 successes/8
      attempts vs standard: 1 success/4 attempts, P = .018), and overall success was
      greater using irrigated catheters (66% vs 33%, P = .019). Mean delivered power
      was slightly higher in irrigated lesions (32.5 W vs 30.2 W, P = .025), and mean
      temperature was much lower (33.5 degrees C vs 59.3 degrees C, P < .001). A
      composite AT intensity score was significantly reduced compared with preablation
      values at 6-month follow-up of all patients. CONCLUSIONS: Ablation of ATs in
      patients with CHD results in symptomatic improvement over short-term follow-up.
      Irrigated ablation may result in higher acute success rates in these patients.

PMID- 15992725
TI  - Irrigated catheter ablation of intraatrial reentrant tachycardia and evaluation
      of new technology.

PMID- 15992726
TI  - Mechanisms of pain associated with internal defibrillation shocks: results of a
      randomized study of shock waveform.
AB  - BACKGROUND: Shock pain has limited the acceptance of the implantable atrial
      cardioverter and is a complication of ventricular implantable cardioverter
      defibrillator therapy. Rounding off of the peak of a shock waveform reduces pain.
      Whether the pain reduction results from reduction in the peak voltage or from the
      rounding has not been established. In other words, does reducing the extreme
      dV/dt (voltage derivative) of the conventional truncated exponential capacitive
      discharge waveform reduce pain? OBJECTIVES: The purpose of this study was to
      compare the relative contributions of peak voltage and waveform shape to pain.
      METHODS: We compared rounded and conventional waveforms with equal peak voltages.
      Eighty-five shocks of 50 to 500 V were delivered to 10 patients requiring atrial
      cardioversion for persistent atrial fibrillation. The patient touched an analog
      pain scale (0-15 cm) and orally reported a pain score on a scale from 0 to 5. An
      observer scored thoracic contractions on a scale from 0 to 5. RESULTS: No
      differences between the rounded and conventional waveform on any scale were noted
      for either univariate or multivariate analyses. However, all three response
      scales were strongly predicted by voltage with r(2) = 0.77 (oral), r(2) = 0.86
      (analog), and r(2) = 0.85 (contraction) after correcting for patient variability
      and including a log voltage term. CONCLUSIONS: Patient pain perception was
      determined primarily by waveform peak voltage and not by the rounding, per se.

PMID- 15992727
TI  - Simplified cardiac resynchronization implantation technique involving right
      access and a triple-guide/single introducer approach.
AB  - BACKGROUND: Biventricular pacing is useful for patients with congestive heart
      failure but has the disadvantage of being a long, user-dependent, highly
      technical procedure. OBJECTIVES: The purpose of this study was to simplify the
      procedure. The simplified technique consists of sinus (CS) venography prior to
      implantation, direct coronary access for the left ventricular (LV) lead without
      use of a left-heart delivery system, and triple-guide/one introducer cephalic
      vein access as the first approach in patients presenting in sinus rhythm.
      METHODS: A cephalic cutdown was performed, and a steerable hydrophilic guidewire
      was introduced in the cephalic vein. A 9Fr introducer was advanced over the
      guidewire, and two other guides were inserted through the introducer. This
      technique allowed for insertion of a right ventricular lead, an LV lead, and an
      atrial lead. RESULTS: One hundred three patients were evaluated from January 2002
      to September 2004. Four implants failed (3.9%). The 7Fr LV lead was successfully
      placed in 99 of 103 patients (96.1%) directly via the 9Fr introducer, without use
      of a dedicated left-heart delivery system. The final position was lateral in 59
      patients, posterolateral in 33, posterior in 4, and anterolateral in 3. Sixty
      patients were in sinus rhythm, 13 were in atrial fibrillation, and 26 had a
      previous pacemaker (n = 21) or defibrillator (n = 5). Triple cephalic vein access
      was possible in 48 of the patients in sinus rhythm (80%). Procedure parameters
      were as follows: LV threshold 0.9 +/- 0.7 V, LV wave amplitude 15 +/- 8 mV, LV
      impedance 790 +/- 232 Omega, skin-to-skin procedure time 76 +/- 33 minutes, and
      fluoroscopy time 23 +/- 19 minutes. Ten complications (10.1%) occurred: 7 lead
      dislodgments (3 within 48 hours and 4 within 6 months) requiring repositioning
      (7.1%), 1 subacute local infection requiring explantation (1%), 1 phrenic nerve
      stimulation (1%), and 1 pneumothorax (1%). The long-term success of biventricular
      pacing was 93.1%. CONCLUSIONS: This study demonstrates that cardiac
      resynchronization therapy implantation can be simplified with the combined use of
      a steerable hydrophilic guidewire, three guides, and one introducer via a right
      cephalic vein, without use of a left-heart delivery system. The triple cephalic
      vein approach yields an 80% implant success rate for patients in sinus rhythm.
      The long-term success of biventricular pacing was 93.1%.

PMID- 15992728
TI  - Quantification of activation patterns during ventricular fibrillation in open
      chest porcine left ventricle and septum.
AB  - BACKGROUND: A single stationary mother rotor has been hypothesized to be
      responsible for maintenance of ventricular fibrillation (VF) in the guinea pig.
      Previous studies have pointed to the ventricular septum as a possible location
      for a mother rotor in the pig heart. OBJECTIVES: The purpose of this study was to
      test the hypothesis that a mother rotor is located in the septum. METHODS: In
      seven open-chest pigs, we mapped the first 20 seconds of electrically induced VF
      simultaneously from the posterior left ventricle (LV) and right side of the
      septum with two electrical arrays. Each array contained 504 electrodes (21 x 24)
      spaced 2 mm apart in the LV and 1.5 mm apart in the septum. RESULTS: The
      percentage of VF wavefronts that formed reentrant circuits was significantly
      lower in the septum (1% +/- 1% [mean +/- SD]) than in the LV (2% +/- 1%). The
      peak frequency during VF also was significantly smaller in the septum (8.6 Hz +/-
      3.0 Hz) than in the LV (10.4 Hz +/- 3.4 Hz). The mean direction of spread of
      activation of VF wavefronts was away from the region where the posterior LV free
      wall intersects the posterior septum in both the LV and septum. CONCLUSIONS: The
      lower incidence of reentry and lower peak frequency in the mapped region of the
      septum than in the LV indicate that a mother rotor is not present in swine on the
      RV side of the septum. The mean directions of the VF activation sequences in the
      LV and septum suggest that if a mother rotor is present during the first 20
      seconds of VF, it exists where the posterior LV free wall joins the septum, the
      region where the posterior papillary muscle inserts.

PMID- 15992729
TI  - In pursuit of the elusive culprit.

PMID- 15992730
TI  - IKs blockade reduces dispersion of repolarization in heart failure.
AB  - BACKGROUND: The slow and rapid (I(Kr)) components of I(K) are major determinants
      of ventricular repolarization. Unlike I(Kr), which is homogeneously expressed
      across the transmural wall, I(Ks) expression is reduced in midmyocardial cells
      and presumably contributes significantly to transmural dispersion of
      repolarization. Increased dispersion of repolarization during pharmacologic
      blockade of I(Kr) is proarrhythmic, primarily due to relatively selective
      prolongation of midmyocardial cell action potential duration (APD). The
      mechanisms underlying proarrhythmia in heart disease associated with impaired
      repolarization, such as heart failure, are unknown. We hypothesize that, in
      contrast to I(Kr) blockade, I(Ks) blockade will have little effect on
      midmyocardial cells and hence decrease dispersion of repolarization in heart
      failure. OBJECTIVES: The purpose of this study was to determine the effect of
      blockade of the slow component of the delayed rectifier current (I(Ks)) on
      arrhythmogenic dispersion of repolarization and proarrhythmia in heart failure.
      METHODS: Optical action potentials were simultaneously recorded from 256 sites
      spanning the transmural wall of the arterially perfused canine wedge preparation.
      Hearts from dogs with heart failure induced by rapid pacing (n = 6) were compared
      with normals (n = 6). RESULTS: Baseline dispersion of repolarization, as measured
      from the range of transmural APD during stimulation at a cycle length of 2,000
      ms, was significantly higher in heart failure (75 +/- 24 ms) compared with
      controls (39 +/- 21 ms, P < .04). I(Ks) blockade with 30 microM chromanol
      decreased dispersion of repolarization by 40% (P < .02) in heart failure,
      reducing it to values found in normals. Decreased dispersion of repolarization
      was due to a larger, relatively selective, drug-induced APD prolongation of
      epicardial (23%) compared with midmyocardial cells (9%, P < .02). VT could not be
      induced in failing hearts under conditions of I(Ks) blockade, and no
      proarrhythmia was observed. CONCLUSION: I(Ks) blockade significantly reduced
      heart failure-induced dispersion of repolarization to values seen in nonfailing
      hearts. By prolonging repolarization without increasing dispersion of
      repolarization, I(Ks) blockade may have antiarrhythmic effects without creating
      proarrhythmia.

PMID- 15992731
TI  - Specific potassium channel blockade for arrhythmia prevention in the ionically
      remodeled failing heart: peril or panacea?

PMID- 15992732
TI  - Common human SCN5A polymorphisms have altered electrophysiology when expressed in
      Q1077 splice variants.
AB  - BACKGROUND: Eight common (>0.5%) polymorphisms of SCN5A have been described in
      the US population. Every human also continuously generates two wild-type (WT)
      splice variants, one with a glutamine residue at position 1077 (Q1077) and one
      lacking this glutamine (Q1077del). One polymorphism (H558R) has been studied in
      both splice variants, five polymorphisms (R34C, R481W, S524Y, P1090L,V1951L) have
      not been previously studied, and two polymorphisms (S1103Y and R1193Q) have been
      studied in only one of the two splice variants. OBJECTIVES: The purpose of this
      study was to examine the electrophysiologic molecular phenotype of the eight
      common polymorphisms in the two human splice variants of SCN5A. METHODS: Currents
      from 16 channels (all polymorphisms in both splice variants) were determined by
      voltage clamp and compared with WT after expression in HEK-293 cells. RESULTS:
      Six of eight polymorphisms showed a distinct phenotype that depended upon the
      background splice variant used for expression. Only R34C and V1951L showed no
      functional differences. S524Y showed a dramatic reduction in current density in
      the Q1077 background similar to that previously described for H558R. Four other
      polymorphisms (R481W, P1090L, S1103Y, R1193Q) showed shifts in activation,
      inactivation, or recovery that depended upon the splice variants. Shifts of a
      similar magnitude have been reported for arrhythmia syndrome mutations and are
      thought to be pathogenic. CONCLUSION: The majority of common human SCN5A
      polymorphisms have a distinct molecular phenotype that depends upon the splice
      variant background. These findings have implications for the interpretation of
      previous studies of arrhythmia mutations. The significance of these findings for
      clinical arrhythmia remains to be elucidated.

PMID- 15992733
TI  - Can common genetic variations combine to produce the long QT syndrome phenotype?

PMID- 15992734
TI  - Pseudoblock and pseudoconduction across the cavotricuspid isthmus.

PMID- 15992735
TI  - Mechanism of eccentric retrograde atrial activation sequence during atypical
      atrioventricular nodal reciprocating tachycardia.

PMID- 15992736
TI  - Refining detection of drug-induced proarrhythmia: QT interval and TRIaD.
AB  - QT interval prolongation is so frequently associated with torsades de pointes
      (TdP) that it has come to be recognized as a surrogate marker of this unique
      tachyarrhythmia. However, not only does TdP not always follow QT interval
      prolongation, but TdP can occur even in the absence of a prolonged QT interval.
      Worse still, even shortening of the QT interval may be associated with serious
      arrhythmias (particularly ventricular tachycardia [VT] and ventricular
      fibrillation [VF]). It appears increasingly probable that the distinction between
      various ventricular tachyarrhythmias may be arbitrary, and drug-induced TdP,
      polymorphic VT, VT, catecholaminergic polymorphic VT, and VF may represent
      discrete entities within a spectrum of drug-induced proarrhythmia. Although they
      are differentiated by the coupling interval and the duration of QT interval, they
      appear to share a common substrate: a set of disturbances of repolarization
      characterized by Triangulation, Reverse use dependency, electrical Instability of
      the action potential, and Dispersion (TRIaD). It is becoming increasingly evident
      that augmentation of TRIaD, rather than changes in the duration of QT interval,
      provides the proarrhythmic substrate. In contrast, when not associated with an
      increase of TRIaD, QT interval prolongation can be an antiarrhythmic property.
      Electrophysiologically, augmentation of TRIaD can be explained by inhibition of
      hERG (human ether-a-go-go related gene) channel. Because drug-induced
      disturbances in repolarization commonly result from inhibition of hERG channels
      or I(Kr), hERG blockade and the resulting prolongation of QT interval are
      important properties of a drug to be studied. However, these need only be a
      concern if associated with TRIaD. More significantly, TRIaD so often precedes
      prolongation of action potential duration or QT interval and ventricular
      tachyarrhythmias that it should be considered a marker of proarrhythmia until
      proven otherwise, even in the absence of QT interval prolongation. Detecting drug
      induced augmentation of TRIaD may offer an additional, more sensitive, and
      accurate indicator of the broader proarrhythmic potential of a drug than may QT
      interval prolongation alone.

PMID- 15992737
TI  - Detection of drug-induced proarrhythmia: balancing preclinical and clinical
      studies.

PMID- 15992738
TI  - Three-dimensional anatomic structure as substrate for ventricular
      tachycardia/ventricular fibrillation.

PMID- 15992739
TI  - Intra-atrial reentrant tachycardia with ambiguous data from activation mapping:
      what to do next?

PMID- 15992740
TI  - Oversensing in a newly implanted dual-chamber implantable cardioverter
      defibrillator: what is the mechanism?

PMID- 15992741
TI  - Atrial lead implantation in the Bachmann bundle.

PMID- 15992742
TI  - "Porcelain pocket": dystrophic calcification of an implantable cardiac
      defibrillator pocket presenting as impending erosion.

PMID- 15992743
TI  - Translation initiation by factor-independent binding of eukaryotic ribosomes to
      internal ribosomal entry sites.
AB  - Two exceptional mechanisms of eukaryotic translation initiation have recently
      been identified that differ fundamentally from the canonical factor-mediated, end
      dependent mechanism of ribosomal attachment to mRNA. Instead, ribosomal 40S
      subunits bind in a factor-independent manner to the internal ribosomal entry site
      (IRES) in an mRNA. These two mechanisms are exemplified by initiation on the
      unrelated approximately 300 nt.-long Hepatitis C virus (HCV) IRES and the
      approximately 200 nt.-long cricket paralysis virus (CrPV) intergenic region (IGR)
      IRES, respectively. Ribosomal binding involves interaction with multiple non
      contiguous sites on these IRESs, and therefore also differs from the factor
      independent attachment of prokaryotic ribosomes to mRNA, which involves base
      pairing to the linear Shine-Dalgarno sequence. The HCV IRES binds to the solvent
      side of the 40S subunit, docks a domain of the IRES into the ribosomal exit (E)
      site and places the initiation codon in the ribosomal peptidyl (P) site.
      Subsequent binding of eIF3 and the eIF2-GTP/initiator tRNA complex to form a 48S
      complex is followed by subunit joining to form an 80S ribosome. The CrPV IRES
      binds to ribosomes in a very different manner, by occupying the ribosomal E and P
      sites in the intersubunit cavity, thereby excluding initiator tRNA. Ribosomes
      enter the elongation stage of translation directly, without any involvement of
      initiator tRNA or initiation factors, following recruitment of aminoacyl-tRNA to
      the ribosomal aminoacyl (A) site and translocation of it to the P site.

PMID- 15992744
TI  - Epistasis and the genetics of human diseases.
AB  - Epistasis or modifier genes, that is, gene-gene interactions of non-allelic
      partners, play a major role in susceptibility to common human diseases. This old
      genetic concept has experienced a major renaissance recently. Interestingly,
      epistatic genes can make the disease less severe, or make it more severe. Hence,
      most diseases are of different intensities in different individuals and in
      different ethnicities. This phenomenon affects sickle-cell anemia carriers and
      other hemoglobinopathies, systemic lupus erythematosus, cystic fibrosis, complex
      autoimmune diseases, venous thromboembolism, and many others. It is likely, and
      fortunate, than 20 years form now, patients entering a medical facility will be
      subjected to a genomic scanning, including pathogenic genes as well as epistatic
      genes.

PMID- 15992745
TI  - Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial
      membrane.
AB  - In many apoptotic responses, pro-apoptotic members of the Bcl-2 family trigger
      the permeabilization of the outer mitochondrial membrane, thereby allowing the
      release of mitochondrial apoptogenic factors that contribute to caspase
      activation in the cytosol. The mechanisms that lead to the activation of pro
      apoptotic Bcl-2 family members and to the permeabilization of the outer
      mitochondrial membrane are not yet completely understood. Here, we attempt to
      summarize our current view of the mechanisms that lead to these events, regarding
      both additional proteins that were recently suggested to be involved, and the
      roles of lipids.

PMID- 15992747
TI  - Formation and structure of food bodies in Cordia nodosa (Boraginaceae).
AB  - Cordia nodosa Lamark (Boraginaceae) is a myrmecophyte (i.e., plants housing ants
      in hollow structures) that provisions associated ants with food bodies (FBs)
      produced 24 h a day. Distributed over all the young parts of the plants, they
      induce ants to forage continually and so to protect the plants. Metabolites are
      stored in the inner cells of C. nodosa FBs as they form. In addition the
      peripheral cells have an extrafloral nectary-like function and secrete a
      substance that covers the FBs. The amalgam of these two functions, distinct in
      other known cases, is discussed taking into account the origin of FBs and
      extrafloral nectaries.

PMID- 15992746
TI  - Analysis of differences in amino acid substitution patterns, using multilevel G
      tests.
AB  - In this paper, a new algorithm is presented, which makes possible multilevel
      comparison of BLOSUM protein substitution matrices based on data from different
      groups of organisms. As an example, a comparison between substitution matrices
      based on data from two groups of bacterial genomes with different GC content is
      presented. Our approach includes evaluating the number of amino acid pairs in
      BLOCKS databases created separately for the two groups of bacteria using protein
      sequences deposited in the COG database. Differences of distributions of amino
      acid pair counts are tested using the chi-squared based G-test. Different
      analysis levels make it possible to distinguish different patterns of amino acid
      substitution. Application of the algorithm reveals statistically significant
      differences in amino acid substitution patterns between AT-rich and GC-rich
      groups of bacterial organisms. The differences are particularly visible in the
      overall substitution pattern, amino acid conservation pattern and in comparison
      of substitution patterns for single amino acids. The algorithm presented in this
      paper can be considered a novel method for multi-level comparison of amino acid
      substitution patterns. The presented approach is not limited to bacterial
      organisms and BLOSUM substitution matrices. Statistically significant differences
      between substitution patterns in the two groups of bacterial organisms with
      respect to amino acid conservation pattern can be the evidence of different rate
      of evolutionary change between AT-rich and GC-rich bacterial organisms.

PMID- 15992748
TI  - [Interaction of intermittent fasting on the cytotoxic effects of nickel in rats
      at puberty].
AB  - This study has been undertaken with the aim of determining if intermittent
      fasting can be considered as a malnutrition that amplifies, according to numerous
      authors, the cytotoxic effects of environmental pollutants. We have used 200 male
      and female rats of 'Wistar' descent (BW approximately 180 g). These rats are
      distributed into two groups: some nourished daily (N) and others nourished one
      day over two (J) during a month. By the end of this month, each group is itself
      split into two subgroups, the first one receiving tap water as drinkable water
      (group NO and JO); the other one receiving the water enriched by the chloride of
      nickel at the rate of 100 mg NiCl2 per litre (groups NNi and JNi). Intermittent
      fasting goes on parallel to treatment during 2, 4, 10, 16, 30 and 60 days. For
      the exploration of the protein of stress (HSP) and of the metallothioneines (MT),
      the nickel is administered by injection at the rate of 4 mg NiCl2 per kg during 1
      and 5 days. Our results show that the mineral seric and renal balance does not
      vary in conditions of intermittent fasting compared with conditions of normal
      nutrition. Our study show than that nickel induced a renal deficiency by
      decreasing the creatinemia and uraemia rate, which is confirmed by the
      histological study, and induced a decrease in the induction of the HSP73 and in
      the synthesis of the (MT). The association of nickel with intermittent fasting
      would inhibit these effects. In conclusion, intermittent fasting does not
      manifest itself as a malnutrition that amplifies the nickel's effects.
      Nevertheless, it seems that the calorific lack provoked by intermittent fasting
      is beneficial to the body by increasing its performances against the cytotoxic
      effects induced by nickel.

PMID- 15992749
TI  - [Palynological evidence of anthropogenic pressure: effect on pollination dynamics
      in the Evian area since the middle Neolithic: the pollen record of La Beunaz (971
      m a.s.l., northern Alps, France)].
AB  - This paper presents a pollen diagram from La Beunaz peat-bog (southeast of Evian,
      Haute-Savoie, France), which provides the first detailed record of human impact
      on vegetation of the southern bank of Lake Geneva since the Middle Neolithic. The
      radiocarbon-dated pollen profile is correlated with micro-charcoal record and
      archaeological data. The results suggest that several phases of deforestations
      since 4615+75/-70 years BP occurred, in relation to human activities
      (agriculture, pastoralism). Tombs and vestiges of lacustrine villages indicate
      that the region was intensively and recurrently occupied by man during at that
      time.

PMID- 15992750
TI  - Further support for the clades obtained by multiple molecular phylogenies in the
      acanthomorph bush.
AB  - Several recent molecular studies have begun to clarify the phylogeny of
      Acanthomorpha (Teleostei), a wide clade of teleost fishes. However, different
      molecular datasets do not agree on a single history of the taxa, probably because
      of marker-specific biases. The 'total-evidence' approach maximizes character
      congruence, but may be biased by a single robust, but non-phylogenetic constraint
      from one dataset. We have therefore taken the approach to analyse also each
      dataset separately prior to their combination, and detect repeated groups: signal
      common to markers is more probably a reflection of shared ancestry than marker
      specific signal. Partial sequences (678+527 base pairs) of exons of the MLL gene
      (Mixed Lineage Leukaemia-like) gene were used, as well as the datasets of Chen et
      al. (ribosomal 28S, rhodopsin gene, mitochondrial 12S and 16S). Most of the
      repeated clades of Chen et al. are supported by the new dataset. Some new groups
      were repeatedly found: a Scarus-Labrus group (clade M), the presence of
      Gasterosteidae as a sister taxon or within the clade Zoarcoidei-Cottoidei (clade
      Is), Polymixia as a sister-group to the clade Zeoidei-Gadiformes (clade O), the
      clade Q grouping Mugiloidei, Cichlidae, Atherinomorpha, Blennioidei and
      Gobiesocoidei; and the interesting clade N, reducing potential sister-groups to
      Tetraodontiformes to either Caproidei, Lophiiformes, Acanthuroidei, Drepanidae,
      Chaetodontidae, and Pomacanthidae.

PMID- 15992751
TI  - Motor vehicle collision risk and driving under the influence of cannabis:
      evidence from adolescents in Atlantic Canada.
AB  - OBJECTIVE: Employing a sample of 6087 senior students in Atlantic Canada, this
      paper examines the relationship between driving under the influence of cannabis
      (DUIC) and motor vehicle collision (MVC) risk. A series of models were analyzed
      adjusting for demographic characteristics, driver experience, and substance use.
      METHODS: Participants were drawn from the 2002/2003 Student Drug Use Survey in
      the Atlantic Provinces, an anonymous cross-sectional survey of adolescent
      students in the Atlantic provinces of Canada. Logistic regression techniques were
      employed in the analysis of unadjusted and adjusted models. RESULTS: Among senior
      students, the prevalence of DUIC in the past year was 15.1% while the prevalence
      of MVCs was 8.1%. The predictors of DUIC were gender, driver experience, use of a
      fake ID, and driving under the influence of alcohol (DUIA). The predictors of MVC
      were gender, driver experience, DUIC, and DUIA. CONCLUSIONS: These findings
      extend our knowledge of DUIC as a socio-legal and public health issue with
      implications on road safety. Effort must be placed on educating new drivers about
      cannabis use in the context of driving.

PMID- 15992752
TI  - Characterization of macular edema from various etiologies by optical coherence
      tomography.
AB  - PURPOSE: To use optical coherence tomography (OCT) to characterize the
      intraretinal changes associated with macular edema (ME) according to its
      etiology. DESIGN: Observational case series. METHODS: Seventy-eight eyes of 78
      patients with ME were examined retrospectively by OCT, using the Humphrey 2000
      OCT system (Humphrey Co., San Leandro, California). ME etiologies were diabetic
      retinopathy (27 cases), central retinal vein occlusion (18 cases), pseudophakia
      (15 cases), posterior uveitis (10 cases), and retinitis pigmentosa (eight cases).
      Macular thickness was measured using OCT mapping software. It was correlated with
      logarithmic visual acuity. RESULTS: In 72 of 78 cases (92%), ME was located in
      the outer retinal layers. Serous retinal detachment was present in 29 of 78 cases
      (37%). It was most frequent in central retinal vein occlusion (10 of 18 cases,
      56%). There were no significant differences in visual acuity (P = .26) or macular
      thickness (P = .95) whether or not serous retinal detachment was combined with
      ME. The posterior hyaloid was partially detached in 17 of 78 cases (22%) of
      overall cases. Serous retinal detachment did not correlate with partial posterior
      hyaloid detachment (P = .6). Mean macular thickness ranged from 506 microm in
      central retinal vein occlusion to 373 microm in retinitis pigmentosa. Visual
      acuity correlated with macular thickness in diabetic retinopathy (R = 0.55; P =
      .0027) and pseudophakia cases (R = 0.66; P = .016). CONCLUSIONS: OCT
      characterized the retinal morphologic changes associated with ME, especially the
      vitreomacular relationship and sub-clinical serous macular detachment. This
      detachment did not correlate with poor visual acuity. Macular thickening only
      correlated with visual loss in diabetic retinopathy and pseudophakia.

PMID- 15992753
TI  - Whole body positron emission tomography/computed tomography staging of metastatic
      choroidal melanoma.
AB  - PURPOSE: To evaluate whole-body positron emission tomography (PET)/computed
      tomography in staging of patients with metastatic choroidal melanoma. DESIGN:
      Interventional non-randomized clinical study. METHODS: Twenty patients were
      referred for whole-body 18-fluoro-2-deoxy-D-glucose (FDG) PET/computed tomography
      imaging because of suspected metastatic choroidal melanoma. PET/computed
      tomography images were studied for the presence and distribution of metastatic
      melanoma. Subsequent biopsies were performed to confirm the presence of
      metastatic disease. RESULTS: Twenty patients underwent PET/computed tomography.
      Eighteen were imaged because of abnormal clinical, hematologic, or radiographic
      screening studies during the course of their follow-up after plaque brachytherapy
      or enucleation. Two were imaged before treatment of their primary tumor.
      PET/computed tomography revealed or confirmed metastatic melanoma in eight (40%)
      of these 20 patients. The mean time from initial diagnosis to metastasis was 47
      months (range 0 to 154). The most common sites for metastases were the liver
      (100%), bone (50%), lung (25%), lymph nodes (25%), and subcutaneous tissue (25%).
      Cardiac, brain, thyroid, and posterior abdominal wall lesions (12.5%) were also
      noted. Six patients (75%) had multiple organ involvement. No false positives were
      noted. PET/computed tomography imaging also detected benign lesions of the bone
      and lymph nodes in three patients (15%). All patients had hepatic metastases and
      liver enzyme assays were abnormal in only one (12.5%) of eight patients.
      CONCLUSIONS: PET/computed tomography imaging is a sensitive tool for the
      detection and localization of hepatic and extra-hepatic (particularly osseous)
      metastatic choroidal melanoma.

PMID- 15992754
TI  - Fellow eye comparison between the 1CU accommodative intraocular lens and the
      Acrysof MA30 monofocal intraocular lens.
AB  - PURPOSE: To examine the near visual clinical performance of an accommodative
      intraocular lens (IOL) when compared with a standard monofocal IOL in a fellow
      eye comparison. DESIGN: Prospective, randomized fellow eye comparison. METHODS:
      Thirty patients (60 eyes) with bilateral cataracts but otherwise normal eyes were
      recruited from a single university hospital cataract waiting list. Patients were
      randomized to receive either the 1CU accommodative IOL in their first eye or the
      Acrysof MA30 monofocal IOL. The alternative lens was then implanted in the second
      eye 4 to 6 weeks later. At all follow-up visits, a full assessment was made of
      distance, near and reading visual performance, and accommodative amplitude.
      RESULTS: Data are available for all patients at 6 months and 20 patients at 1
      year. At 6 months, no difference was found in distance-corrected visual acuity
      between the two IOLs. Of the 1CU eyes, nine patients (30%) could read J6 or
      better at a reading speed of 80 words/min or better. In these nine patients, the
      mean difference in the amplitude of accommodation between the two eyes was 0.71
      diopters. CONCLUSIONS: No measurable variable distinguished eyes that developed
      functional reading vision from those that did not. The accommodative IOL appears
      to produce improved near vision in some eyes, but it does not work in all eyes,
      and in eyes where there is apparent accommodation, there is a discrepancy between
      subjective reading performance and the modest measured increase of accommodative
      amplitude.

PMID- 15992755
TI  - Visual outcome and risk factors for light perception and no light perception
      vision after vitrectomy for diabetic retinopathy.
AB  - PURPOSE: To assess the visual outcome following vitrectomy for diabetic
      retinopathy compared with previous studies; to evaluate risk factors for light
      perception (LP) and no light perception (NLP) vision after diabetic vitrectomy.
      DESIGN: Retrospective medical record review. METHODS: The charts of 100
      consecutive patients who underwent vitrectomy for proliferative diabetic
      retinopathy between November 1, 1997, and November 30, 1998, were reviewed.
      Surgical technique included standard pars plana vitrectomy with combination of
      delamination and segmentation of gliotic tractional membranes using bimanual
      techniques. All patients had post-operative follow-up of at least 12 months.
      Several factors were analyzed for their effect on poor visual outcome (LP and
      NLP) using Fisher's exact test. RESULTS: Post-vitrectomy, 73% of diabetic
      patients had stable or improved vision; 16% had worsened but functional vision,
      defined as worse but still >or= 20/400; 4% had worsened but ambulatory vision,
      defined as worse but still count fingers (CF) or hand motion (HM); and 7% had
      poor visual outcome, LP or NLP. Resultant visual acuity was >or=20/40 in 38% of
      patients, 20/50 to 20/100 in 34%, 20/120 to CF in 18%, HM in 3%, LP in 4%, and
      NLP in 3%. Risk factors for eyes with LP and NLP vision included pre-operative
      iris neovascularization (INV), P = .05, post-operative INV, P = .02, post
      operative macular ischemia, P = .0001, and post-operative vitreous hemorrhage
      (VH), P = .02. CONCLUSIONS: Pre-operative and post-operative INV, post-operative
      macular ischemia, and post-operative VH appear to be risk factors for LP and NLP
      vision following diabetic vitrectomy, whereas overall improvements in surgical
      technique and visual outcome continue to be reported.

PMID- 15992756
TI  - Regression of serous macular detachment after intravitreal triamcinolone
      acetonide in patients with diabetic macular edema.
AB  - PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide on serous
      macular detachment in eyes with diabetic macular edema. DESIGN: Interventional
      case series. METHODS: The study population comprised twenty eyes of 20 patients
      with diabetic macular edema (12 men, eight women), aged 48 to 76 years. The
      eligibility criteria for this study included clinically detectable macular edema
      in which the presence of serous macular detachment was documented by optical
      coherence tomography. After intravitreal injection of 0.1 ml (4 mg) triamcinolone
      acetonide, visual and anatomic responses were observed. RESULTS: In all eyes,
      after an injection of triamcinolone acetonide, macular edema and serous macular
      detachment regressed. At 3 and 6 months, macular edema and serous macular
      detachment had recurred in eight (40%) and nine eyes (45%), respectively.
      Patients with recurrence were re-treated. No eyes lost vision at 1 month, and all
      eyes showed improvement. At 3 months, no eyes had lost vision from baseline, and
      17 eyes (85%) showed improvement. At 6 months, again no eyes had lost vision from
      baseline, and 16 eyes (80%) maintained improved visual acuity. CONCLUSION:
      Intravitreal triamcinolone acetonide is an effective treatment for serous macular
      detachment in patients with diabetic macular edema.

PMID- 15992757
TI  - Critical sources of error in colorimetric assay for UDP-N-acetylglucosamine
      pyrophosphorylase.

PMID- 15992758
TI  - High-throughput scintillation proximity assay for transglutaminase activity
      measurement.
AB  - Members of the transglutaminase enzyme family are involved in a broad range of
      biological phenomena, including haemostasis, apoptosis, semen coagulation, skin
      formation, and wound healing. A new and rapid method for measurement of
      transglutaminase activity is described in this article. The enzyme links tritium
      labeled putrescine to biotinylated oligoglutamine, and the tritiated peptide is
      bound to a streptavidin-coated microtiter plate permanently covered by a thin
      layer of scintillant. Only the radioisotope incorporated into the peptide
      substrate is close enough to the scintillant molecules for photons to be
      produced. The signal generation depends on the transglutaminase activity, and it
      can be detected by appropriate light-measuring instrumentation without separation
      steps. The assay is sensitive, specific, linear at concentrations of tissue
      transglutaminase between 0.05 and 1.6m U/ml, and suitable for high-throughput
      measurements.

PMID- 15992759
TI  - A continuous spectrophotometric assay for dimethylarginine
      dimethylaminohydrolase.

PMID- 15992760
TI  - Capillary electrophoretic analysis of advanced glycation endproducts formed from
      the reaction of reducing sugars with the amino group of glucosamine.
AB  - Glucosamine (GlcN) is an amino sugar sold over-the-counter and is widely used as
      a dietary supplement to relieve symptoms of osteoarthritis. It is not known
      whether it is the GlcN alone or one of its many possible nonenzymatic glycation
      products that is responsible for this effect. The current study demonstrates that
      reducing sugars form advanced glycation endproducts (AGEs) with GlcN and, as a
      result, decrease GlcN autocondensation by reducing the availability of the GlcN
      amino group. Capillary electrophoresis (CE) was used to analyze the in vitro
      Maillard reaction of GlcN with glyceraldehyde (GA), glucose (Glc), and fructose
      (Fru) as well as their inhibition of GlcN autocondensation under physiological
      conditions. Formation of AGEs was monitored by UV and fluorescence spectroscopy.
      Major components were separated by CE using a bare capillary and UV detection at
      214 nm. AGE species were separated by HPLC and were complementary to the CE
      results. The effects of sugar concentration and incubation time on the AGE
      profile are also reported for each of the GlcN reducing sugar model systems. A
      simple and rapid CE method was developed to analyze the AGE formation in this
      initial report of the reaction of reducing sugars with the amino group of GlcN.

PMID- 15992761
TI  - Use of low-melting-point primers for bisulfite genomic sequencing: analysis of
      the H37 lung cancer tumor suppressor gene promoter.

PMID- 15992762
TI  - [Diabetes Type I therapy through transplantation].
AB  - Diabetes is one of the most common chronic diseases in our society. While insulin
      treatment for diabetes type I could delay and reduce the incidence of diabetic
      complications, it is associated with an increased risk of severe hypoglycemia. To
      restore physiologic insulin metabolism, transplantation of insulin producing
      cells (pancreatic Beta cells) represent the sole available therapy. It could be
      done either through pancreas or islet of Langerhans transplantation. In this
      paper, we review actual knowledge regarding these two types of transplantations.

PMID- 15992763
TI  - [Autopsies and surgery].

PMID- 15992764
TI  - Specific distribution of VEGF-F in Viperinae snake venoms: isolation and
      characterization of a VGEF-F from the venom of Daboia russelli siamensis.
AB  - Vascular endothelial growth factor exerts multiple functions through binding to
      two distinct receptor tyrosine kinases, Flt-1 and KDR. We previously demonstrated
      that snake venom VEGFs, designated VEGF-Fs, exhibit potent biological activities
      when compared with VEGF165 and that they selectively recognize KDR. We herein
      report the screening of several snake venoms for VEGF-Fs using antibodies against
      vammin and HF, VEGF-Fs derived from the venom of Vipera ammodytes ammodytes and
      Vipera aspis aspis, respectively. Specific immunoreactivity was observed in the
      venoms of Vipera and Daboia species. The present results suggest that VEGF-Fs are
      specific components of venoms from the Viperinae snakes that inhabit Europe,
      India, and Asia. We also report the isolation and characterization of an
      additional VEGF-F from Daboia russelli siamensis venom.

PMID- 15992765
TI  - A new hyperpolarization-activated, cyclic nucleotide-gated channel from sea
      urchin sperm flagella.
AB  - A sea urchin sperm flagellar hyperpolarization-activated, cyclic nucleotide-gated
      (HCN) channel is known (SpHCN1) that is modulated by cAMP. Here, we describe a
      second flagellar HCN channel (SpHCN2) cloned from the same sea urchin species.
      SpHCN2 is 638 amino acids compared to 767 for SpHCN1. SpHCN2 has all the domains
      of an HCN channel, including six transmembrane segments (S1-S6), the ion pore,
      and the cyclic nucleotide-binding domain. The two full-length proteins are 33%
      identical and 51% similar. The six transmembrane segments vary from 46-79%
      identity. S4, which is the voltage sensor, is 79% identical between the two
      proteins. The ion selectivity filter sequence is GYG in the ion pore of SpHCN1
      and GFG in SpHCN2. By sequence, SpHCN2 is 73.5kDa, but it migrates on SDS-PAGE at
      64kDa. Western immunoblots show localization to flagella, which is confirmed by
      immunofluorescence. A neighbor-joining tree shows that SpHCN2 is basal to all
      known HCN channels. SpHCN2 might be the simplest pacemaker channel yet
      discovered.

PMID- 15992766
TI  - Promoter-, cell-, and ligand-specific transactivation responses of the VDRB1
      isoform.
AB  - The vitamin D receptor (VDR) mediates the effects of 1,25(OH)(2)D(3), the active
      form of vitamin D. The human VDRB1 isoform differs from the originally described
      VDR by an N-terminal extension of 50 amino acids. Here we investigate cell-,
      promoter-, and ligand-specific transactivation by the VDRB1 isoform.
      Transactivation by these isoforms of the cytochrome P450 CYP24 promoter was
      compared in kidney (HEK293 and COS1), tumor-derived colon (Caco-2, LS174T, and
      HCT15), and mammary (HS578T and MCF7) cell lines. VDRB1 transactivation in
      response to 1,25(OH)(2)D(3) was greater in COS1 and HCT15 cells (145%), lower in
      HEK293 and Caco-2 cells (70-85%) and similar in other cell lines tested. By
      contrast, on the cytochrome P450 CYP3A4 promoter, 1,25(OH)(2)D(3)-induced VDRB1
      transactivation was significantly lower than VDRA in Caco-2 (68%), but comparable
      to VDRA in HEK293 and COS1 cells. Ligand-dependence of VDRB1 differential
      transactivation was investigated using the secondary bile acid lithocholic acid
      (LCA). On the CYP24 promoter LCA-induced transactivation was similar for both
      isoforms in COS1, whereas in Caco-2 and HEK293 cells VDRB1 was less active. On
      the CYP3A4 promoter, LCA activation of VDRB1 was comparable to VDRA in all the
      cell lines tested. Mutational analysis indicated that both the 1,25(OH)(2)D(3)
      and LCA-regulated activities of both VDR isoforms required a functional ligand
      dependent activation function (AF-2) domain. In gel shift assays VDR:DNA complex
      formation was stronger in the presence of 1,25(OH)(2)D(3) than with LCA. These
      results indicate that regulation of VDRB1 transactivation activity is dependent
      on cellular context, promoter, and the nature of the ligand.

PMID- 15992767
TI  - Gene expression profiling of the preclinical scrapie-infected hippocampus.
AB  - The molecular events that underlie prion disease neuropathology remain poorly
      defined. Within the hippocampus of the ME7/CV mouse scrapie model, profound CA1
      neuronal loss occurs between 160 and 180 days post-infection (dpi). To elucidate
      the molecular events that may contribute to this neuronal loss, we have applied
      Affymetrix high-density oligonucleotide probe arrays to the study of ME7-infected
      hippocampal gene expression at 170 dpi. The study has identified 78 genes that
      are differentially expressed greater than 1.5-fold within the preclinical ME7
      infected hippocampus prior to the profound late stage glial cell activation. The
      results indicate oxidative and endoplasmic reticulum (ER) stress, activated ER
      and mitochondrial apoptosis pathways, and activated cholesterol biosynthesis
      within the scrapie-infected hippocampus, and offer insight into the molecular
      events which underlie the neuropathology.

PMID- 15992768
TI  - Susceptibility of human and rat neural cell lines to infection by SARS
      coronavirus.
AB  - Pathological characterization of autopsied tissues from patients with SARS
      revealed severe damage in restricted tissues, such as lung, with no apparent cell
      damage in other tissues, such as intestine and brain. Here, we examined the
      susceptibility of neural cell lines of human (OL) and rat (C6) origins to SARS
      associated coronavirus. Both of the neural cell lines showed no apparent
      cytopathic effects (CPE) by infection but produced virus with infectivity of 10(2
      5) per ml, in sharp contrast to the production by infected Vero E6 cells of
      >10(9) per ml that showed a lytic infection with characteristic rounding CPE.
      Interestingly, the infection of intestinal cell line CaCo-2 also induced no
      apparent CPE, with production of the virus at a slightly lower level as that of
      the Vero E6 cell culture. Notably, the cellular receptor for the virus,
      angiotensin-converting enzyme 2 was expressed at similar levels on Vero E6 and
      CaCo-2 cells, but at undetectable levels on OL and C6 cells.

PMID- 15992769
TI  - Regulatory mechanisms underlying pheromone biosynthesis activating neuropeptide
      (PBAN)-induced internalization of the Bombyx mori PBAN receptor.
AB  - Internalization of the Bombyx mori pheromone biosynthesis activating neuropeptide
      receptor (PBANR) has been attributed to the presence of a 67 amino acid C
      terminal extension absent in PBANRs from Helicoverpa. To identify the structural
      motif(s) responsible for internalization, a series of truncation mutants fused
      with enhanced green fluorescent protein were constructed and transiently
      expressed in insect Sf9 cells. Confocal microscopy analyses revealed that
      truncation at Gly357 severely inhibited internalization while truncation at
      Gln367 did not, indicating that the PBANR internalization motif resides between
      Gly357-Gln367. Alanine substitution studies suggest that Tyr360 and Leu363 may
      constitute a YXXL endosomal targeting motif that facilitates endocytosis,
      however, this motif does not appear to be the primary determinant; an indication
      that multiple sites are involved. Furthermore, we determined that internalization
      of the PBANR proceeds via a clathrin-dependent pathway, is dependent on the
      influx of extracellular calcium, and likely does not involve a G protein-coupled
      receptor kinase.

PMID- 15992770
TI  - Expression of the C-terminal domain of novel human SR-A1 protein: interaction
      with the CTD domain of RNA polymerase II.
AB  - We have recently cloned a new member of the human Ser/Arg-rich superfamily (SR)
      of pre-mRNA splicing factors, SR-A1. Members of the SR family of proteins have
      been shown to interact with the C-terminal domain (CTD) of the large subunit of
      RNA polymerase II, and participate in pre-mRNA splicing. The largest subunit of
      RNA polymerase II contains at the carboxy-terminus a peculiar repetitive sequence
      that consists of 52 tandem repeats of the consensus motif Tyr-Ser-Pro-Thr-Ser-Pro
      Ser, referred to as the CTD. There is evidence that SR protein splicing factors
      are involved in cancer pathobiology through their involvement in alternative
      processing events. The CTD of human SR-A1 protein (aa 1187-1312), containing a
      conserved CTD-interaction domain and bearing a decahistidine (His10) tag was
      produced by DNA recombinant overexpression techniques in Escherichia coli from
      the vector pET16b and it was localized in the periplasmic space. The protein was
      further purified using a HiTrap chelating column and its circular dichroism
      spectra indicate that it assumes a defined structure in solution. Performing a
      pull-down assay we proved that the novel SR-A1 [1187-1312 His10] protein
      interacts with the CTD domain of RNA polymerase II.

PMID- 15992771
TI  - A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite
      outgrowth.
AB  - Alpha-Pal/NRF-1 is a critical regulator of the promoter of human IAP/CD47 gene, a
      gene related to memory formation in rodents. However, its function in neurons was
      unknown. We found that stable or transient expression of full-length alpha
      Pal/NRF-1 in human neuroblastoma IMR-32 cells significantly induced neurite
      outgrowth and increased the length of neurites both in medium containing 10%
      fetal bovine serum and in serum-free medium. In contrast, the dominant-negative
      mutant of alpha-Pal/NRF-1 inhibited the induction and extension of neurites.
      Ectopic expression of full-length alpha-Pal/NRF-1 also increased the induction of
      neurite outgrowth in primary mouse cortical neurons. The IAP antisense cDNA
      significantly inhibited the increase of neurite outgrowth by alpha-Pal/NRF-1.
      These findings indicate that a novel function of alpha-Pal/NRF-1 is to regulate
      neuronal differentiation, and that this function is mediated partly via its
      downstream IAP gene.

PMID- 15992772
TI  - How actin crosslinking and bundling proteins cooperate to generate an enhanced
      cell mechanical response.
AB  - Actin-crosslinking proteins organize actin filaments into dynamic and complex
      subcellular scaffolds that orchestrate important mechanical functions, including
      cell motility and adhesion. Recent mutation studies have shown that individual
      crosslinking proteins often play seemingly non-essential roles, leading to the
      hypothesis that they have considerable redundancy in function. We report live
      cell, in vitro, and theoretical studies testing the mechanical role of the two
      ubiquitous actin-crosslinking proteins, alpha-actinin and fascin, which co
      localize to stress fibers and the basis of filopodia. Using live-cell particle
      tracking microrheology, we show that the addition of alpha-actinin and fascin
      elicits a cell mechanical response that is significantly greater than that
      originated by alpha-actinin or fascin alone. These live-cell measurements are
      supported by quantitative rheological measurements with reconstituted actin
      filament networks containing pure proteins that show that alpha-actinin and
      fascin can work in concert to generate enhanced cell stiffness. Computational
      simulations using finite element modeling qualitatively reproduce and explain the
      functional synergy of alpha-actinin and fascin. These findings highlight the
      cooperative activity of fascin and alpha-actinin and provide a strong rationale
      that an evolutionary advantage might be conferred by the cooperative action of
      multiple actin-crosslinking proteins with overlapping but non-identical
      biochemical properties. Thus the combination of structural proteins with similar
      function can provide the cell with unique properties that are required for
      biologically optimal responses.

PMID- 15992773
TI  - In vivo photosystem I reduction in thermophilic and mesophilic cyanobacteria: the
      thermal resistance of the process is limited by factors other than the unfolding
      of the partners.
AB  - Photosystem I reduction by plastocyanin and cytochrome c(6) in cyanobacteria has
      been extensively studied in vitro, but much less information is provided on this
      process inside the cell. Here, we report an analysis of the electron transfer
      from both plastocyanin and cytochrome c(6) to photosystem I in intact cells of
      several cyanobacterial species, including a comparative study of the temperature
      effect in mesophilic and thermophilic organisms. Our data show that cytochrome
      c(6) reduces photosystem I by following a reaction mechanism involving complex
      formation, whereas the copper-protein follows a simpler collisional mechanism.
      These results contrast with previous kinetic studies in vitro. The effect of
      temperature on photosystem I reduction leads us to conclude that the thermal
      resistance of this process is determined by factors other than the proper
      stability of the protein partners.

PMID- 15992774
TI  - F-actin has a very high calorimetric unfolding enthalpy.
AB  - The thermal unfolding of F-actin was studied using differential scanning
      calorimetry. Heat denatures F-actin in two steps. The first is endothermic and
      corresponds to the unfolding of the peptide chain, while the second is exothermic
      and is due to the aggregation of the unfolded molecules. The aspect of the
      thermogram is influenced by the concentration of the protein. For concentrations
      around 1mg/ml, the steps are superimposed, while the two steps are separated at
      very low concentrations. It thus becomes possible to estimate the calorimetric
      enthalpy for the unfolding step. The enthalpy of unfolding is 64 MJ/mol, or 1400
      J/g. This value is considerably higher than those mentioned in the literature for
      the denaturation of actin and other proteins, which are in the range of 25-30
      J/g. The large amount of energy required to unfold the molecule of F-actin could
      be an adaptation of its role as a protein that transmits forces, and consequently
      must be very resistant to mechanical constraints.

PMID- 15992775
TI  - Minimal sodium channel pore consisting of S5-P-S6 segments preserves
      intracellular pharmacology.
AB  - We studied the properties of a sodium channel comprised only of S5-P-S6 region of
      the rat sodium channel alpha-subunit Nav1.4 (micro1pore). Results obtained in HEK
      cell lines permanently transfected with the sodium channel alpha-subunit or with
      the micro1pore were compared with data of the native HEK cells. Sodium channel
      blockers, tetrodotoxin and tetracaine, protect cells transfected with the
      complete sodium channel against death produced by incubation with veratridine.
      Veratridine-induced cell death in cell lines expressing the micro1pore construct
      is antagonised by tetracaine, but not by tetrodotoxin. Whole-cell conductance
      also increases in the presence of veratridine in micro1pore transfected cells and
      tetracaine inhibits these currents. Our pharmacological and electrophysiological
      data suggest that micro1pore keeps binding sites for veratridine and tetracaine,
      but not for TTX, and reconstitutes the permeation pathway for Na+ ions.

PMID- 15992776
TI  - Constitutive activity of human angiotensin II type-1 receptors by Gq
      overexpression.
AB  - We have developed an inducible HEK293/Tet-On cell line that transiently expresses
      both FLAG-tagged human angiotensin II type-I receptors (FLAG-hAT(1)R) and
      G(q)alpha G protein subunits in response to doxycycline. High and tightly
      regulated levels of FLAG-hAT(1)R (740+/-57 fmol/mg protein) and G(q)alpha (36
      fold increase compared with non-induced cells) overexpression were consistently
      achieved. We investigated the possibility of using an inducible system to
      increase the proportion of constitutively active wild-type FLAG-hAT(1)Rs by
      overexpressing G(q)alpha. Following doxycycline treatment, we observed no
      significant change in the apparent binding affinity or potency (coupling
      efficiency) of angiotensin II, though significant increases in the intrinsic
      activity of several partial agonists were observed, indicative of constitutive
      activity. DUP753 (10 microM), a suggested inverse agonist, did not inhibit the
      enhanced level of basal (agonist-independent) activity. The data suggest that the
      resting equilibrium of hAT(1) receptors between the inactive (R) and active (R*)
      forms is predominantly weighted towards the inactive conformation.

PMID- 15992777
TI  - MN-cadherin and its novel variant are transiently expressed in chick embryo
      spinal cord.
AB  - To isolate cDNAs that are involved in limb-motoneuron development, we compared
      mRNAs of lumbar and thoracic motoneurons purified from spinal cord of E4 chick
      embryo by differential display. In situ hybridization demonstrated that one of
      cDNAs is expressed exclusively in lateral motor column in spinal cord from E4 to
      E10. We identified two mRNA variants for the cDNA by library screening. The long
      form (788 amino acids) was identical to chick MN-cadherin. The short variant (543
      amino acids) lacks the first two of five extracellular domains of MN-cadherin,
      which commonly exist in classical cadherins. The amino acid sequence of the short
      form is identical to that of the carboxyl terminal MN-cadherin, except for the
      distinct signal sequence. The ratio of mRNA of short form to long form was 1-20.
      cDNA transfection study revealed that the long form but not the short form MN
      cadherin had cell adhesion activity.

PMID- 15992778
TI  - Silencing of yellow head virus replication in penaeid shrimp cells by dsRNA.
AB  - RNA interference (RNAi) has been shown to inhibit viral replication in some
      animals and plants. Whether the RNAi is functional in shrimp remains to be
      demonstrated. In vitro transcribed dsRNAs of YHV helicase, polymerase, protease,
      gp116, and gp64 were transfected into shrimp primary cell culture and found to
      inhibit YHV replication. dsRNA targeted to nonstructural genes (protease,
      polymerase, and helicase) effectively inhibited YHV replication. Those targeted
      structural genes (gp116 and gp64) were the least effective. These findings are
      the first evidence that RNAi-mediated gene silencing is operative in shrimp
      cells. This could be a powerful tool for studying gene function and to develop
      effective control of viral infection in shrimp.

PMID- 15992779
TI  - Targeting neutrophil collagenase/matrix metalloproteinase-8 and gelatinase
      B/matrix metalloproteinase-9 with a peptidomimetic inhibitor protects against
      endotoxin shock.
AB  - Gram-negative sepsis, bacterial meningitis and endotoxin shock are life
      threatening disorders, associated with the rapid release of neutrophil enzymes.
      Neutrophil collagenase/matrix metalloproteinase-8 (MMP-8) and gelatinase B/matrix
      metalloproteinase-9 (MMP-9) are contained in granules, are quickly exocytosed
      upon granulocyte activation and efficiently cleave intact and denatured
      collagens, respectively. Genetic ablation of gelatinase B protects against
      endotoxin-induced mortality. Therefore, we designed and synthesized a
      peptidomimetic gelatinase B inhibitor Regasepin1, and compared the selectivity
      for the collagenases MMP-1, MMP-8 and MMP-13. Regasepin1 was found to inhibit,
      almost to the same degree, the neutrophil enzymes MMP-8 and MMP-9 and the
      monocytic tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE/ADAM
      17) in vitro. With the use of mass spectrometry analysis, the plasma half-life of
      inhibitor levels was determined after an intraperitoneal bolus injection in mice.
      Plasma peak levels of the inhibitor were reached at 50 min after intraperitoneal
      injection and the subsequent half-life in the circulation exceeded 40 min.
      Regasepin1 protected mice against lethal endotoxinemia by intraperitoneal and
      intravenous injection routes. This proves the principle that early neutrophil MMP
      inhibition followed by TACE blockade may become a treatment strategy of gram
      negative sepsis, endotoxinemia and other life-threatening inflammatory reactions.

PMID- 15992780
TI  - Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa
      measured by positron emission tomography and [11c]raclopride.
AB  - BACKGROUND: Several lines of evidence support the possibility that disturbances
      of dopamine (DA) function could contribute to alterations of weight, feeding,
      motor activity, and reward in anorexia nervosa (AN). METHODS: To assess possibly
      trait-related disturbances but avoid confounding effects of malnutrition, 10
      women who were recovered from AN (REC AN) were compared with 12 healthy control
      women (CW). Positron emission tomography with [(11)C]raclopride was used to
      assess DA D2/D3 receptor binding. RESULTS: The women who were recovered from AN
      had significantly higher [(11)C]raclopride binding potential in the antero
      ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was
      positively related to harm avoidance in the dorsal caudate and dorsal putamen.
      CONCLUSIONS: These data lend support for the possibility that decreased
      intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is
      associated with AN and might contribute to the characteristic harm avoidance or
      increased physical activity found in AN. Most intriguing is the possibility that
      individuals with AN might have a DA related disturbance of reward mechanisms
      contributing to altered hedonics of feeding behavior and their ascetic, anhedonic
      temperament.

PMID- 15992781
TI  - Succinate causes oxidative damage through N-methyl-D-aspartate-mediated
      mechanisms.
AB  - In this study we investigated whether succinate, the accumulating substrate in
      succinate dehydrogenase (SDH) deficiencies and SDH inhibitor intoxication, causes
      lipoperoxidation and protein carbonylation, and if NMDA receptors are involved in
      the succinate-induced oxidative damage. Adult male mice (30-40 g) received an
      intracerebroventricular injection of succinic acid (0.7, 1.0 and 1.7 micromol/5
      microl) or 0.9% NaCl (5 microl) and had their exploratory behavior assessed in an
      open field for 10 min. Succinate (0.7 and 1.0 micromol/5 microl) decreased
      locomotor activity behavior and increased thiobarbituric acid reactive substances
      (TBARS) and protein carbonylation in the forebrain. Conversely, 1.7 micromol of
      succinate did not alter locomotor activity or oxidative damage parameters. The
      involvement of NMDA receptors in the succinate-induced increase of total protein
      carbonylation content and exploratory behavior inhibition was assessed by co
      administrating MK-801 (7 nmol/2.5 microl icv), a noncompetitive NMDA receptor
      antagonist, with succinate (1 micromol/2.5 microl icv). The co-administration of
      MK-801 protected against succinate-induced increase of total protein
      carbonylation and decrease of locomotor activity. These results suggest the
      involvement of NMDA receptors in these effects of succinate, which may of
      particular relevance for succinate-accumulating conditions, such as SDH
      inhibitors intoxication and inherited SDH deficiencies.

PMID- 15992782
TI  - Behavioral differences in a rotenone-induced hemiparkinsonian rat model developed
      following intranigral or median forebrain bundle infusion.
AB  - A mitochondrial complex-I inhibitor, rotenone was unilaterally infused into the
      substantia nigra pars compacta (SNpc) or median forebrain bundle (MFB) to create
      hemiparkinsonian animal models and investigated spontaneous and drug-induced
      stereotypic rotations, as well as certain postural behaviors in Sprague-Dawley
      rats. Animals infused intranigrally, but not intra-MFB, with rotenone exhibited
      spontaneous contralateral rotations immediately after recovery from anesthesia.
      Head position bias and elevated body swing test showed insignificant
      contralateral bias in animals with nigral damage but a significant ipsilateral
      bias in MFB-lesioned rats. General motor activity of the animals was reduced in
      both the groups as indicated by reduced performance on a Plus-Maze.
      Intranigrally, rotenone-infused animals exhibited progressive ipsilateral
      rotations when challenged with d-amphetamine on the 7th, 14th, 21st, and 28th
      days or with apomorphine on 9th, 16th, 23rd, and 30th days. However, animals that
      received rotenone in MFB exhibited ipsilateral or contralateral rotations when
      challenged respectively with d-amphetamine or apomorphine only in the 5th week
      (28th and 30th days). Stereotaxic administration of rotenone into SNpc or MFB
      caused a significant loss of dopamine in the ipsilateral striatum (>80% in SNpc;
      >95% in MFB), when assayed employing an HPLC equipped with electrochemical
      detector on the 32nd day. Neuronal loss in SNpc was confirmed in coronal sections
      stained with cresyl violet and revealed extension of lesion towards SN pars
      reticulata, in SNpc-infused animals. Our results demonstrate that rotenone
      induced neurodegeneration is a slow, yet progressive process similar to that in
      idiopathic Parkinson's disease and unlike that observed in other classical
      neurotoxin-mediated lesions which are abrupt and developed in few hours to days.
      Thus, intranigral or intra-MFB infusion of rotenone could be used for producing
      hemiparkinsonian animal models in rats. These findings further suggest that,
      while both d-amphetamine and apomorphine-induced stereotypic rotations could be
      used as a valuable behavioral assay procedure to test novel drugs against
      Parkinson's disease, yet apomorpine-induced contralateral bias in turning is a
      reliable indicator of specific destruction in nigrostriatal pathway and
      development of postsynaptic dopamine receptor supersensitivity.

PMID- 15992783
TI  - Chemoenzymatic synthesis of 6omega -modified maltooligosaccharides from
      cyclodextrin derivatives.
AB  - Regioselectively substituted maltooligosaccharides were prepared by enzymatic
      transformation of modified cyclodextrins by using simultaneously two different
      enzymes: cyclodextrin glucanotransferase (CGTase) and amyloglucosidase.
      Oligosaccharides were obtained in very good yields and their structures were
      identified by 1D and 2D NMR spectroscopy. These results provided new information
      about the specificity of the catalytic sites of CGTase and amyloglucosidase. They
      also offered new ways for the synthesis of regioselectively modified
      maltooligosaccharides.

PMID- 15992784
TI  - Structural studies on the exopolysaccharide from Erwinia persicina.
AB  - The Gram-negative bacterial strain HKI 0380 was isolated from biofilms located on
      palaeolithic rock paintings in the Cave of Bats in Zuheros, southern Spain. It
      was identified as the phytopathogenic Erwinia persicina and attracted attention
      due to the production of considerable quantities of slime. The acidic
      exopolysaccharide produced by the E. persicina was studied after O-deacylation by
      sugar and methylation analyses, along with (1)H and (13)C NMR spectroscopy. The
      following structure of the branched pentasaccharide repeating unit of the O
      deacylated exopolysaccharide was established: [carbohydrate structure: see text].

PMID- 15992785
TI  - Regiochemistry of epoxide ring opening in methyl 2,3-anhydro-4-azido-4-deoxy
      alpha- and beta-L-lyxopyranosides.
AB  - Methyl 2,3-anhydro-4-O-methanesulfonyl-alpha-d-ribopyranoside (12) was prepared
      through a new six-step sequence starting from d-arabinose. Chemical behaviour of
      12 was further studied under solvolytic conditions and in the presence of azide
      anion as a nucleophile. Factors governing the regiochemistry of epoxide ring
      opening are briefly discussed.

PMID- 15992786
TI  - Oral L-arginine supplementation ameliorates urinary risk factors and kinetic
      modulation of Tamm-Horsfall glycoprotein in experimental hyperoxaluric rats.
AB  - BACKGROUND: Oral supplementation of l-arginine (l-arg) is found to be beneficial
      in many kidney disorders. We determined whether l-arg supplementation safeguards
      the renal epithelial cell damage induced by hyperoxaluria with excretion of
      urinary marker enzymes and lithogenic salts with special reference to Tamm
      Horsfall glycoprotein (THP). METHODS: Hyperoxaluria was induced by 0.75% ethylene
      glycol (EG) in drinking water. l-Arg was co-supplemented at the dose of 1.25 g/kg
      b.w. orally for 28 days. At the end of experimental period, 24-h urine samples
      were collected in all the experimental groups. Isolation and purification of THP
      was carried in rat urine and were subjected to spectrophotometric crystallization
      assay and calcium-(14)C-oxalate binding studies. Determination of the lithogenic
      risk factors like calcium, oxalate, phosphorus, citrate, and marker enzymes such
      as lactate dehydrogenase (LDH) and gamma-glutamyltransferase (gamma-GT) were
      carried out in the collected urine sample. RESULTS: Urinary excretion of calcium
      and oxalate was significantly increased in EG-treated rats. In l-arg supplemented
      hyperoxaluric rats, these concentrations were significantly (p<0.001) decreased
      when compared to that of hyperoxaluric rats, and were moderately elevated from
      that of control rats. The activities of urinary marker enzymes, both LDH and
      gamma-GT were 2-fold increased in EG-treated rats, when compared to control rats,
      but these values were maintained near normal in l-arg supplemented EG-treated
      rats. Citrate excretion was enhanced in the l-arg co-supplemented hyperoxaluric
      rats. In spectrophotometric crystallization assay system, l-arg supplemented rat
      THP showed inhibition in nucleation and aggregation phases, whereas EG-treated
      rat THP showed promotion of both calcium oxalate nucleation and aggregation
      phases. In calcium-(14)C-oxalate binding assay, THP derived from hyperoxaluric
      rats exhibited 2-fold increase (p<0.001) in the Ca*Ox binding when compared to
      control and l-arg supplemented animals. CONCLUSIONS: l-Arg could act as a potent
      antilithic agent, by increasing the level of citrate in the hyperoxaluria-induced
      rats and decreasing calcium oxalate binding to the THP. l-Arg also effectively
      prevents the deposition of calcium oxalate crystals by curtailing the renal
      epithelial damage and protein oxidation as evidenced by the normal activities of
      urinary marker enzymes in l-arg supplemented hyperoxaluric rats.

PMID- 15992787
TI  - CSF markers in sleep neurobiology.
AB  - The cerebrospinal fluid has been used in the study of normal and pathological
      conditions of the central nervous system for more than a century. CSF analysis
      has also been applied to the study of sleep and its disorders but methodological
      aspects have often limited the results. The discovery of the hypocretin system
      (also known as orexin system) and its involvement in the pathophysiology of
      narcolepsy has opened a new field in the diagnosis of hypersomnia by CSF analysis
      and has revived the interest on this subject in sleep medicine. Older and new
      lines of research involving CSF measurement of hypocretin and other
      neurotransmitters in sleep and its disorders are reviewed.

PMID- 15992788
TI  - Urinary and plasma organic acids and amino acids in chronic fatigue syndrome.
AB  - Previous work by others have suggested the occurrence of one or more chemical or
      metabolic 'markers' for ME/CFS including specific amino acids and organic acids
      and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere
      that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially
      derivatised serine and have suggested and demonstrated that the analytical
      methods used were unsuitable to identify or to accurately quantify urinary
      metabolites. We have now made a detailed analysis of plasma and urinary amino
      acids and of urinary organic acids from patients with ME/CFS and from three
      control groups. Fasting blood plasma and timed urine samples were obtained from
      31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with
      depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino
      acids and urinary organic acids were determined using established and validated
      methods and data compared by statistical analysis. None of the previously
      reported abnormalities in urinary amino acids or of organic acids could be
      confirmed. Results however provide some evidence in patients with ME/CFS for
      underlying inflammatory disease and for reduced intramuscular collagen with a
      lowered threshold for muscle micro-injury. These factors in combination may
      provide a basis for the fatigue and muscle pain that are the major symptoms in
      these patients.

PMID- 15992789
TI  - Urate oxidation during percutaneous transluminal coronary angioplasty and
      thrombolysis in patients with coronary artery disease.
AB  - Thrombolysis and percutaneous transluminal coronary angioplasty (PTCA) are kinds
      of procedures that can be used to restore the blood flow of previously ischemic
      myocardium that can be the result of excessive production of reactive oxygen and
      nitrogen species, such as superoxide and hydroxyl radical, hypochlorous acid and
      peroxynitrite. Reaction of urate with some of these potent oxidants results in
      allantoin production. In this study, we measured the serum allantoin levels, an
      oxidation product of urate, and "in vivo" marker of free radical generation in
      reperfusion of ischemic myocardium. After an overnight fasting state, blood
      samples were collected from 35 patients with coronary occlusive diseases (7 women
      and 28 men) and 31 healthy subjects (8 women and 23 men). Serum allantoin and
      urate levels were measured by a GC-MS method. Serum allantoin levels of patients
      on PTCA therapy (mean+/-SD, 27.4 +/- 15.2 micromol/l) and thrombolytic therapy
      (24.6 +/- 8.6 micromol/l) were significantly higher than those of the patients
      without therapy (15.8 +/- 6.2 micromol/l, p < 0.05 with PTCA and p < 0.006 with
      thrombolysis) and healthy controls (12.6 +/- 6.3 micromol/l, p < 0.002 with PTCA
      and p < 0.0001 with thrombolysis). Although serum urate levels in PTCA (380.1 +/-
      72.6 micromol/l) and thrombolysis (359.5 +/- 60.0 micromol/l) were higher than
      those in the non-therapy patients (336.6 +/- 53.8 micromol/l) and controls (318.3
      +/- 81.0 micromol/l), there were no significant differences among groups (p >
      0.05). The results of the study are consistent with others which have
      demonstrated, higher urate levels are associated with coronary occlusive
      diseases. Our data support the hypothesis that generation of ROS occurs during
      myocardial reperfusion. Increased allantoin levels may be used as an index of
      increased oxidative stress during reperfusion.

PMID- 15992791
TI  - Decisions, decisions: infant language learning when multiple generalizations are
      possible.
AB  - Two experiments presented infants with artificial language input in which at
      least two generalizations were logically possible. The results demonstrate that
      infants made one of the two generalizations tested, the one that was most
      statistically consistent with the particular subset of the data they received.
      The experiments shed light on how learners might go about solving the induction
      problem for human language.

PMID- 15992790
TI  - Apolipoprotein B-100 kinetics and static plasma indices of triglyceride-rich
      lipoprotein metabolism in overweight men.
AB  - OBJECTIVE: We examined the association of plasma apolipoprotein (apoB) B-48,
      remnant-like particle (RLP)-cholesterol and non-HDL cholesterol concentrations
      with apoB-100 kinetics in overweight-obese men. METHODS AND RESULTS: Very-low
      density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low
      density lipoprotein (LDL) apoB-100 kinetics were measured in 53 men (BMI 33 +/- 4
      kg/m(2)) using stable isotopes and multicompartmental modeling to estimate
      production rate (PR) and fractional catabolic rate (FCR). Fasting apoB-48 and RLP
      cholesterol concentrations were measured using immunoassays. In univariate
      regression, apoB-48 and RLP-cholesterol were inversely associated with VLDL-apoB
      100 FCR and IDL-apoB-100 FCR (P < 0.01 for all), but not with VLDL-, IDL- and LDL
      apoB-100 PRs. Plasma non-HDL-cholesterol concentration was significantly and
      positively associated with the secretion rate of VLDL-apoB-100 (P < 0.05), and
      inversely correlated with the FCR of LDL-apoB-100 (P < 0.01). CONCLUSIONS: Our
      findings suggest that in overweight-obese men plasma concentrations of apoB-48,
      RLP-cholesterol and non-HDL-cholesterol are partly dependent on catabolism of
      apoB-100 containing lipoproteins.

PMID- 15992793
TI  - Early and late processes in syllogistic reasoning: evidence from eye-movements.
AB  - An eye-movement monitoring experiment was carried out to examine the effects of
      the difficulty of the problem (simple versus complex problems) and the type of
      figure (figure 1 or figure 4) on the time course of processing categorical
      syllogisms. The results showed that the course of influence for these two factors
      is different. We found early processing effects for the figure but not for the
      difficulty of the syllogism and later processing effects for both the figure and
      the difficulty. These results lend support to the Model Theory (Johnson-Laird, P.
      N., Byrne, R. M. J. (1991). Deduction. Hillsdale, New Jersey: LEA.) as opposed to
      other theories of reasoning (Chater, N., Oaksford, M. (1999). The probability
      heuristics model of syllogistic reasoning. Cognitive Psychology, 38, 191-258;
      Rips, L. J. (1994). The psychology of proof. Cambridge, MA: MIT Press; Rips, L.
      J. (1994). The psychology of proof. Cambridge, MA: MIT Press).

PMID- 15992794
TI  - The role of phonological activation in the visual semantic retrieval of Chinese
      characters.
AB  - The Stroop paradigm was used to examine the role of phonological activation in
      semantic access and its development in reading Chinese characters. Subjects (age
      7-23 years) of different reading ability were asked to name the display color of
      Chinese characters. The characters were displayed in four different colors: red,
      yellow, blue and green. There were five types of relationships between a
      character and its display color: semantically congruent, phonologically
      congruent, semantically incongruent, phonologically incongruent and neutral. In
      addition to the classical Stroop effects, interference and facilitation effects
      from the homophones of color characters were also observed. The younger children
      and those with lower reading ability exhibited stronger Stroop effects. These
      findings suggest that phonological codes are activated automatically in Chinese
      character recognition. Furthermore, there is more phonological activation in the
      semantic retrieval of children in lower grades and those with lower reading
      ability.

PMID- 15992795
TI  - Conversion of columnar to stratified squamous epithelium in the developing mouse
      oesophagus.
AB  - The mouse embryonic oesophagus is initially lined with a simple columnar
      epithelial layer which changes during the course of development to a stratified
      squamous tissue. To study the mechanism of this transition, we developed an in
      vitro model, based on oesophageal explants isolated from E11.5d mouse embryos,
      which fully recapitulates the normal in vivo development. In this system, the
      columnar epithelial markers cytokeratins 8 and 18 (K8, 18) were strongly
      expressed at the beginning of the culture period and decreased in the basal layer
      of the epithelium at around 5 days of culture. Expression of K8 + 18 persisted in
      the suprabasal layers of the stratified epithelium for several more days. In
      contrast, the stratified squamous epithelial marker cytokeratin 14 (K14) was
      absent at the beginning, and cells expressing it progressively appeared within
      the basal layer from day 5 to day 9 of culture. The two possible mechanisms for
      the change are (1) a direct conversion of columnar cells to the basal layer cells
      of the squamous epithelium; (2) an overgrowth of columnar by squamous cells. Our
      results show that the first mechanism is operative. Firstly, co-staining for K8
      and K14 demonstrates that some cells express both markers during the transition
      period. Secondly, after electroporation of a construct containing the K14
      promoter driving nuclear GFP into the epithelium of E15.5 oesophagus, some cells
      expressed both K8 and GFP. Thirdly, there is no preferential loss of the columnar
      cells by apoptosis. Fourthly, inhibitors of apoptosis do not affect the process.
      Finally, inhibitors of cell division do not affect the process. In terms of the
      molecular mechanism, inhibitor studies suggest that de novo DNA methylation is
      required for the loss of the K8 expression but not for the acquisition of the K14
      expression. The results show that, in normal development, the squamous epithelium
      arises from the columnar epithelium by a direct conversion process.

PMID- 15992796
TI  - An investigation of the relationship between air emissions of volatile organic
      compounds and the incidence of cancer in Indiana counties.
AB  - Cancer is a health endpoint influenced by a multitude of factors, including
      genetic history, individual behavior, and environmental insults. The ubiquity of
      toxicants in the environment has raised questions about the extent of their role
      in causing cancer in humans. More specifically, it is desirable to understand the
      cancer incidence due to airborne toxicants in anthropogenic pollution. One
      particular class of such pollutants is volatile organic compounds (VOCs). This
      paper reports an epidemiological investigation of the incidence of cancer in the
      92 counties of Indiana. We evaluated the relationship between the amount of VOCs
      released in each county, as reported by the Toxic Release Inventory, and the
      county-by-county incidence of various types of cancer, especially those of less
      common organ systems not directly associated with the absorption or distribution
      of toxicants. Our evaluation considered chlorinated versus nonchlorinated
      emissions as well as stack versus fugitive emissions. We evaluated three models:
      linear, quadratic, and polynomial. Of these, the quadratic model appeared to be
      the best predictor (highest r2) for most endpoints for which there was a positive
      correlation. However, the linear model was the most sensitive (lowest P-value)
      for skin, melanoma, and endocrine-related cancers, including female genital
      system cancers. Our results indicate a relationship between emissions of VOCs and
      the incidence of some types of cancers. Most notable were strong correlations
      between VOC emissions and cancers of the brain, nervous system, endocrine system,
      and skin.

PMID- 15992797
TI  - Breast cancer cell-targeted oxidative stress: enhancement of cancer cell uptake
      of conjugated linoleic acid, activation of p53, and inhibition of proliferation.
AB  - We investigated the mechanism of inhibition of cell proliferation by mixed
      isomers of CLA (9-cis, 11-trans CLA; 10-trans, 12-cis CLA) on human, non
      tumorigenic MCF10A cells that were derived from mammary ductal epithelial cells
      and MCF7 cells that were derived from a well differentiation mammary
      adenocarcinoma. When treated in the log phase of growth, the uptake of CLA by
      MCF7 exceeded the levels measured in MCF10A cells. Treatment with CLA in the
      presence of HPO doubled the incorporation of CLA in MCF7 cells, independent of
      the isomer, but reduced the incorporation of CLA by MCF10A cells. CLA caused
      tumor cell-targeted increased expression of 4-hydroxy-2-nonenal (4HNE), a product
      of lipid peroxidation, and decreased proliferation in MCF7 cells, as measured by
      the incorporation of bromodeoxyuridine (BrdU) and expression of phosphorylated
      histone H3, and the effects of CLA in combination with HPO on mitosis were
      greater than the effects of either agent alone. Decreased cell proliferation in
      CLA-treated MCF7 cells coincided with increased nuclear localization of
      phosphorylated, activated p53 protein, and decreased nuclear localization of the
      transcription factor FKHRSer256. Importantly, CLA-treated MCF7 cells were more
      sensitive than MCF10A cells to HPO-induced 4HNE, expression of p53, and decreased
      mitotic activity. These studies suggest that tumor cell-targeted increased
      sensitivity to oxidative stress and activation of p53 play important roles in the
      regulation of human breast cancer cell proliferation by CLA.

PMID- 15992798
TI  - Fibronectin fragmentation promotes alpha4beta1 integrin-mediated contraction of a
      fibrin-fibronectin provisional matrix.
AB  - In injured tissues, the fibrin-fibronectin (FN) provisional matrix provides a
      framework for cell adhesion, migration, and repair. Effective repair and
      remodeling require a proper balance between extracellular matrix (ECM)
      deposition, contraction, and turnover. We utilized a three-dimensional (3D)
      fibrin-FN provisional matrix model to determine the contributions of the FN
      binding integrin receptors alpha5beta1 and alpha4beta1 to matrix contraction.
      CHOalpha5 cells expressing alpha5beta1, a receptor for FN's RGD cell-binding
      domain, were highly contractile, and cells were well spread on a 3D fibrin-FN
      matrix. In contrast, CHOalpha4 cells expressing the alpha4beta1 receptor for FN's
      alternatively spliced V region attached less efficiently to FN and were deficient
      in fibrin-FN matrix contraction. Surprisingly, cell adhesion and matrix
      contraction by CHOalpha4 cells were dramatically enhanced, to levels equivalent
      to CHOalpha5 cells, when proteolyzed FN was used in place of intact FN in the
      fibrin-FN matrix. Similar enhancement was observed when ligand binding by
      alpha4beta1 integrins was activated by treatment with Mn(++), but not by
      stimulation of actin organization with LPA. Therefore, alpha4beta1-dependent cell
      responses to the provisional matrix are modulated by cleavage of matrix
      components.

PMID- 15992799
TI  - Expression profile of an operationally-defined neural stem cell clone.
AB  - Neural stem cells (NSCs) are the most primordial and least committed cells of the
      nervous system, the cells that exist before regional specification develops.
      Because immunocytochemically-detectable markers that are sufficiently specific
      and sensitive to define an NSC have not yet been fully defined, we have taken the
      strong view that, to be termed a "stem cell" in the nervous system--in contrast
      to a "progenitor" or "precursor" (whose lineage commitment is further restricted)
      -a single neuroectodermally-derived cell must fulfill an operational definition
      that is essentially similar to that used in hematopoiesis. In other words, it
      must possess the following functional properties: (1) "Multipotency", i.e., the
      ability to yield mature cells in all three fundamental neural lineages throughout
      the nervous system--neurons (of all subtypes), astrocytes (of all types),
      oligodendrocytes--in multiple regional and developmental contexts and in a region
      and developmental stage-appropriate manner. (2) The ability to populate a
      developing region and/or repopulate an ablated or degenerated region of the
      nervous system with appropriate cell types. (3) The ability to be serially
      transplanted. (4) "Self-renewal", i.e., the ability to produce daughter cells
      (including new NSCs) with identical properties and potential. Having identified a
      murine neural cell clone that fulfills this strict operational definition--in
      contrast to other studies that used less rigorous or non-operational criteria for
      defining an NSC (e.g., the "neurosphere" assay)--we then examined, by comparing
      gene expression profiles, the relationship such a cell might have to (a) a
      multipotent somatic stem cell from another organ system (the hematopoietic stem
      cell [HSC]); (b) a pluripotent stem cell derived from the inner cell mass and
      hence without organ assignment (an embryonic stem cell); (c) neural cells
      isolated and maintained primarily as neurospheres but without having been
      subjected to the above mentioned operational screen ("CNS-derived neurospheres").
      ESCs, HSCs, and operationally-defined NSCs--all of which have been identified not
      only by markers but by functional assays in their respective systems and whose
      state of differentiation could be synchronized--shared a large number of genes.
      Although, as expected, the most stem-like genes were expressed by ESCs, NSCs and
      HSCs shared a number of genes. CNS-derived neurospheres, on the other hand,
      expressed fewer "stem-like" genes held in common by the other operationally
      defined stem cell populations. Rather they displayed a profile more consistent
      with differentiated neural cells. (Genes of neural identity were shared with the
      NSC clone.) Interestingly, when the operationally-defined NSC clone was cultured
      as a neurosphere (rather than in monolayer), its expression pattern shifted from
      a "stem-like" pattern towards a more "differentiated" one, suggesting that the
      neurosphere, without functional validation, may be a poor model for predicting
      stem cell attributes because it consists of heterogeneous populations of cells,
      only a small proportion of which are truly "stem-like". Furthermore, when
      operational definitions are employed, a common set of stem-like genes does emerge
      across both embryonic and somatic stem cells of various organ systems, including
      the nervous system.

PMID- 15992800
TI  - Reproductive experience differentially affects spatial reference and working
      memory performance in the mother.
AB  - The transition to motherhood results in a number of hormonal, neurological, and
      behavioral changes necessary to ensure offspring survival. Once motherhood is
      established, further neurological and behavioral changes may result with
      additional parity and mothering. Recent research has shown that motherhood
      enhances both hippocampal-dependent learning and memory and oxytocin-induced long
      term potentiation, suggesting that the hippocampus is affected by mothering. In
      turn, degree of maternal behavior, either high or low, has been shown to affect
      spatial learning and memory performance in adult offspring. The present
      experiment aimed to investigate the effect of reproductive experience (nulli-,
      primi-, and multiparity and mothering) and degree of maternal behavior on
      hippocampus-dependent learning and memory in the mother. Results show that
      regardless of error type, primiparous rats make fewer errors compared to
      nulliparous rats, while multiparous rats show a trend towards making fewer errors
      compared to nulliparous rats. In addition, mothers who spend less time licking
      and nursing offspring had fewer reference memory errors. Perhaps the enhanced
      learning and memory in the inexperienced, new mother allows her to effectively
      acquire the suite of maternal behaviors necessary to ensure offspring survival
      and achieve reproductive success with subsequent reproductive experience.

PMID- 15992801
TI  - Historical perspective: Hormonal regulation of behaviors in amphibians.
AB  - This review focuses on research into the hormonal control of behaviors in
      amphibians that was conducted prior to the 21st century. Most advances in this
      field come from studies of a limited number of species and investigations into
      the hormonal mechanisms that regulate reproductive behaviors in male frogs and
      salamanders. From this earlier research, we highlight five main generalizations
      or conclusions. (1) Based on studies of vocalization behaviors in anurans,
      testicular androgens induce developmental changes in cartilage and muscles fibers
      in the larynx and thereby masculinize peripheral structures that influence the
      properties of advertisement calls by males. (2) Gonadal steroid hormones act to
      enhance reproductive behaviors in adult amphibians, but causal relationships are
      not as well established in amphibians as in birds and mammals. Research into the
      relationships between testicular androgens and male behaviors, mainly using
      castration/steroid treatment studies, generally supports the conclusion that
      androgens are necessary but not sufficient to enhance male behaviors. (3)
      Prolactin acts synergistically with androgens and induces reproductive
      development, sexual behaviors, and pheromone production. This interaction between
      prolactin and gonadal steroids helps to explain why androgens alone sometimes
      fail to stimulate amphibian behaviors. (4) Vasotocin also plays an important role
      and enhances specific types of behaviors in amphibians (frog calling, receptivity
      in female frogs, amplectic clasping in newts, and non-clasping courtship
      behaviors). Gonadal steroids typically act to maintain behavioral responses to
      vasotocin. Vasotocin modulates behavioral responses, at least in part, by acting
      within the brain on sensory pathways that detect sexual stimuli and on motor
      pathways that control behavioral responses. (5) Corticosterone acts as a potent
      and rapid suppressor of reproductive behaviors during periods of acute stress.
      These rapid stress-induced changes in behaviors use non-genomic mechanisms and
      membrane-associated corticosterone receptors.

PMID- 15992802
TI  - Are the maximum shortening velocity and the shape parameter in a Hill-type model
      of whole muscle related to activation?
AB  - Mathematical models of the inter-relationship of muscle force, velocity, and
      activation are useful in forward dynamic simulations of human movement tasks. The
      objective of this work was to determine whether the parameters (maximum
      shortening velocity V(max) and shape parameter k) of a Hill-type muscle model,
      interrelating muscle force, velocity, and activation, are themselves dependent on
      the activation. To fulfill this objective, surface EMG signals from four muscles,
      as well as the kinematics and kinetics of the arm, were recorded from 14 subjects
      who performed rapid-release elbow extension tasks at 25%, 50%, 75%, and 100%
      activation (MVC). The experimental elbow flexion angle was tracked by a forward
      dynamic simulation of the task in which V(max) and k of the triceps brachii were
      varied at each activation level to minimize the difference between the simulated
      and experimental elbow flexion angle. Because a preliminary analysis demonstrated
      no dependency of k on activation, additional simulations were performed with
      constant k values of 0.15, 0.20, and 0.25. The optimized values of V(max)
      normalized to the average value within a subject were then regressed onto the
      activation. Normalized V(max) depended significantly on the activation (p<0.001)
      for all values of k. Furthermore, the estimated V(max) values were not sensitive
      to the selected k value. The results support the use of Hill-type models in which
      V(max) depends on activation in forward dynamic simulations modeling muscles with
      mixed fiber-type composition recruited in the range of 25-100% activation. The
      use of more accurate models will lend greater confidence to the results of
      forward dynamic simulations.

PMID- 15992803
TI  - Biomechanics of single zonal chondrocytes.
AB  - Articular cartilage has a distinct zonal architecture, and previous work has
      shown that chondrocytes from different zones exhibit variations in gene
      expression and biosynthesis. In this study, the material properties of single
      chondrocytes from the superficial and middle/deep zones of bovine distal
      metatarsal articular cartilage were determined using unconfined compression and
      digital videocapture. To determine the viscoelastic properties of zonal
      chondrocytes, unconfined creep compression experiments were performed and the
      resulting creep curves of individual cells were fit using a standard linear
      viscoelastic solid model. In the model, a fixed value of the Poisson's ratio was
      used, determined optically from direct compression of middle/deep chondrocytes.
      The two approaches used in this study yielded the following average material
      properties of single chondrocytes: Poisson's ratio of 0.26+/-0.08, instantaneous
      modulus of 1.06+/-0.82 kPa, relaxed modulus of 0.78+/-0.58 kPa, and apparent
      viscosity of 4.08+/-7.20 kPa s. Superficial zone chondrocytes were found to be
      significantly stiffer than middle/deep zone chondrocytes. Attachment time did not
      affect the stiffness of the cells. The zonal variation in viscoelastic properties
      may result from the distinct mechanical environments experienced by the cells in
      vivo. Identifying intrinsic differences in the biomechanics of superficial and
      middle/deep zone chondrocytes is an important component in understanding how
      biomechanics influence articular cartilage health and disease.

PMID- 15992804
TI  - Agreement between two experimental measures or between experiment and theory.

PMID- 15992805
TI  - Optimal control simulations reveal mechanisms by which arm movement improves
      standing long jump performance.
AB  - Optimal control simulations of the standing long jump were developed to gain
      insight into the mechanisms of enhanced performance due to arm motion. The
      activations that maximize standing long jump distance of a joint torque actuated
      model were determined for jumps with free and restricted arm movement. The
      simulated jump distance was 40 cm greater when arm movement was free (2.00 m)
      than when it was restricted (1.60 m). The majority of the performance improvement
      in the free arm jump was due to the 15% increase (3.30 vs. 2.86 m/s) in the take
      off velocity of the center of gravity. Some of the performance improvement in the
      free arm jump was attributable to the ability of the jumper to swing the arms
      backwards during the flight phase to alleviate excessive forward rotation and
      position the body segments properly for landing. In restricted arm jumps, the
      excessive forward rotation was avoided by "holding back" during the propulsive
      phase and reducing the activation levels of the ankle, knee, and hip joint torque
      actuators. In addition, swinging the arm segments allowed the lower body joint
      torque actuators to perform 26 J more work in the free arm jump. However, the
      most significant contribution to developing greater take-off velocity came from
      the additional 80 J work done by the shoulder actuator in the jump with free arm
      movement.

PMID- 15992807
TI  - New approach to determination of surface heterogeneity of adsorbents and
      catalysts from the temperature programmed desorption (TPD) technique: one step
      beyond the condensation approximation (CA) method.
AB  - Recovery of the desorption activation energy distribution from the experimental
      temperature programmed desorption (TPD) spectra is among the most difficult
      problems of adsorption science. Since the heterogeneity effects strongly
      influence on transport, diffusion, and catalytic reaction time, the estimation of
      their magnitude is very important for practical purposes. Up to the present,
      several theories have been used for the interpretation of the TPD results. Almost
      all advanced theoretical approaches take into account the effect of surface
      disorder (heterogeneity in desorption activation energy); however, they ignore
      the numerical difficulties coming from the "ill-posed" character of the linear
      Fredholm integral equations appearing in the theoretical description of the TPD
      results. Thus, there is a growing interest in developing novel methods supported
      by powerful numerical algorithms taking this into account. In the current study
      we propose a new approach and consider the theoretical aspect as well as
      numerical problems appearing in the TPD analysis. Our modeling is based on the
      well-known and generally accepted "absolute rate theory," which has been used
      extensively for the interpretation of TPD results. We propose and verify
      (applying computer simulations) the new advanced numerical hybrid type algorithms
      taking into account the heterogeneity effects. They seem to be very promising in
      TPD spectra analysis. The stability of the proposed advanced numerical methods is
      confirmed by the computer simulation experiments, and the results are compared
      with those obtained from the condensation approximation (CA) method.

PMID- 15992806
TI  - Mixed monolayers of Bauhinia monandra and concanavalin A lectins with
      phospholipids, part II.
AB  - Isotherms of surface pressure and surface potential versus mean molecular area
      for dibehenoylphosphatidylcholine (DBPC), dipalmitoylphosphatidylcholine (DPPC),
      dipalmitoylphosphatidylethanolamine (DPPE), and dioleoylphosphatidylcholine
      (DOPC) monolayers were shown to be greatly modified when these lipids were
      cospread with either Bauhinia monandra (BmoLL) or Concanavalin A (Con A) lectins.
      For the binary films of DBPC, DPPC, and DPPE cospread with each of these two
      lectins, there was both a displacement of the Pi-A and DeltaV-A isotherms toward
      higher molecular areas relative to pure lipids and an increase in the maximum
      surface potential values relative to the DeltaV-A relationships observed for the
      corresponding single-lectin systems. Both effects can be understood in terms of
      the occurrence of an explicit interaction between the lipids and the lectins. The
      plots of the corresponding compressibilities versus molecular areas reveal that,
      for all lipids but DOPC, the extent of this interaction was always larger for
      BmoLL than for Con A. The DPPC and DPPE mixed films with BmoLL differed in
      compressibility. Owing to the small DPPE polar headgroup, the DPPE-BmoLL film was
      much more incompressible than the DPPC-BmoLL mixed monolayer. However, for the
      DOPC-BmoLL and DOPC-Con A mixed films there was no evidence that an interaction
      between the lectins and the lipid took place, a fact attributed to the
      unsaturated character in the DOPC aliphatic chains, which leads to an expanded Pi
      A isotherm.

PMID- 15992808
TI  - Kinetics and equilibrium adsorption of Cu(II), Cd(II), and Ni(II) ions by
      chitosan functionalized with 2[-bis-(pyridylmethyl)aminomethyl]-4-methyl-6
      formylphenol.
AB  - Chitosan biopolymer chemically modified with the complexation agent 2[-bis
      (pyridylmethyl)aminomethyl]-4-methyl-6-formylphenol (BPMAMF) was employed to
      study the kinetics and the equilibrium adsorption of Cu(II), Cd(II), and Ni(II)
      metal ions as functions of the pH solution. The maximum adsorption of Cu(II) was
      found at pH 6.0, while the Cd(II) and Ni(II) maximum adsorption occurred in
      acidic media, at pH 2.0 and 3.0, respectively. The kinetics was evaluated
      utilizing the pseudo-first-order and pseudo-second-order equation models and the
      equilibrium data were analyzed by Langmuir and Freundlich isotherms models. The
      adsorption kinetics follows the mechanism of the pseudo-second-order equation for
      all studied systems and this mechanism suggests that the adsorption rate of metal
      ions by CHS-BPMAMF depends on the number of ions on the adsorbent surface, as
      well as on their number at equilibrium. The best interpretation for the
      equilibrium data was given by the Langmuir isotherm and the maximum adsorption
      capacities were 109 mg g-1 for Cu(II), 38.5 mg g-1 for Cd(II), and 9.6 mg g-1 for
      Ni(II). The obtained results show that chitosan modified with BPMAMF ligand
      presented higher adsorption capacity for Cu(II) in all studied pH ranges.

PMID- 15992809
TI  - FastDC derived from human monocytes within 48 h effectively prime tumor antigen
      specific cytotoxic T cells.
AB  - Previously, we have shown that dendritic cells (DCs) with full T-cell stimulatory
      capacity can be derived from human monocytes after 48 h of in vitro culture
      (FastDC). Compared to a standard 7-day protocol, this new strategy not only
      reduces the time span and the amount of recombinant cytokines required, but may
      also resemble DC development in vivo more closely. Using a melanoma antigen
      model, we show here that FastDC prime CTL responses against tumor antigens as
      effectively as standard monocyte-derived DCs (moDCs). FastDC and moDCs derived
      from monocytes of HLA-A2(+) donors were loaded with the melanoma-associated, HLA
      A(*)0201-restricted peptide Melan-A and cocultured with autologous CD3(+) T
      cells. After two weekly restimulations with freshly prepared, peptide-loaded
      FastDC or moDCs, binding of CD8(+) T cells to fluorescently labeled MHC-I/Melan-A
      peptide complexes and intracellular cytokine staining revealed that the two DC
      preparations had an equal capacity to prime Melan-A-specific, IFN-gamma producing
      CD8(+) T cells. CTLs derived from cocultures with FastDC lysed Melan-A-loaded T2
      cells even more effectively than CTLs primed by moDCs. Comparative analysis also
      revealed that FastDC possess an equal capacity to migrate in response to the
      chemokine receptor CCR-7 ligand 6Ckine. Importantly, DCs can be generated with
      higher yield and purity using the FastDC-protocol. The reliability and efficacy
      of this new strategy for DC development from monocytes may facilitate clinical
      investigation of DC-based tumor immunotherapy.

PMID- 15992810
TI  - Affinity ranking of antibodies using flow cytometry: application in antibody
      phage display-based target discovery.
AB  - Application of antibody phage display to the identification of cell surface
      antigens with restricted expression patterns is often complicated by the
      inability to demonstrate specific binding to a certain cell type. The specificity
      of an antibody can only be properly assessed when the antibody is of sufficient
      high affinity to detect low-density antigens on cell surfaces. Therefore, a
      robust and simple assay for the prediction of relative antibody affinities was
      developed and compared to data obtained using surface plasmon resonance (SPR)
      technology. A panel of eight anti-CD46 antibody fragments with different
      affinities was selected from phage display libraries and reformatted into
      complete human IgG1 molecules. SPR was used to determine K(D) values for these
      antibodies. The association and dissociation of the antibodies for binding to
      CD46 expressed on cell surfaces were analysed using FACS-based assays. We show
      that ranking of the antibodies based on FACS data correlates well with ranking
      based on K(D) values as measured by SPR and can therefore be used to discriminate
      between high- and low-affinity antibodies. Finally, we show that a low-affinity
      antibody may only detect high expression levels of a surface marker while failing
      to detect lower expression levels of this molecule, which may lead to a false
      interpretation of antibody specificity.

PMID- 15992811
TI  - Glycosylated recombinant human XCL1/lymphotactin exhibits enhanced biologic
      activity.
AB  - Chemokines are a family of small, secreted chemoattractant cytokines that
      regulate distribution and function of leukocytes during immune responses. While
      most chemokines are members of the CC or CXC subgroups, XCL1, also known as
      lymphotactin, is the sole member of the C subgroup. XCL1 is produced by activated
      CD8(+) T cells, NK cells, gammadelta T cells, and mast cells. XCL1 differs from
      other chemokines in that it contains only a single disulfide bond and a mucin
      like domain at its carboxy terminus that is glycosylated. Understanding the
      biologic functions of chemokines has largely depended upon expression of these
      recombinant molecules in E. coli. To examine the effects of glycosylation on the
      biologic activity of XCL1, we designed constructs for expression of human XCL1 in
      insect S2 cells. Comparison of this material with that expressed in E. coli
      reveals that glycosylation significantly increases the biologic activity of XCL1.

PMID- 15992812
TI  - Validation of computer-assisted, pixel-based analysis of multiple-colour
      immunofluorescence histology.
AB  - Developments in immunohistology allow the routine simultaneous use on tissue
      sections of three monoclonal antibodies, tagged with different fluorochromes.
      Such staining can identify seven different cell populations and the limiting
      factor is rapid, reliable and reproducible analysis. Future reliance on computer
      assisted analysis of digitised images depends on validation against manual
      counting, often viewed as the 'gold standard'. In this study images were
      digitised from sections of normal porcine skin, inflamed skin and tonsil,
      simultaneously stained with three monoclonal antibodies. Combinations of staining
      were quantified by four manual counts and by pixel-based area measurement. On
      individual images, the correlation between automated and manual measurements was
      poor. Despite this, the concordance between manual and automated measurements in
      the means and variances of tissues was good, and both techniques identified the
      same changes in inflamed versus normal tissues. In addition, pixel-based counting
      permitted statistical analysis of co-localisation of cell types in tissue
      sections. We conclude that automated counting is acceptable for the assessment of
      tissues, is faster and provides less opportunity for observer variation than
      manual counting. We also demonstrate that the technique is applicable where more
      than three fluorochromes are used such that manual counting becomes essentially
      impossible.

PMID- 15992813
TI  - Molecular genotyping of the murine H-2K MHC class I allele.
AB  - An increasing number of genetically modified mouse mutants are employed in
      immunological research. Many experiments require the crossbreeding of various
      mouse lines and screening for the genetic background of the offspring. Analysis
      for various immunological phenotypes such as the MHC class I haplotype is usually
      performed by FACS analysis of peripheral blood lymphocytes. Here, we report a PCR
      based technique for the differentiation of the MHC class I H-2K(k) and the H
      2K(b) haplotype. Advantages of this method are cost efficiency and rapidity in
      particular when multiple genetic variables such as the disruption of a gene,
      transgenesis or the MHC haplotype are to be tested.

PMID- 15992814
TI  - A flow cytometry-based assay for the measurement of protein regulation of E
      cadherin-mediated adhesion.
AB  - Epithelial (E)-cadherin is a transmembrane protein that mediates calcium
      dependent cell adhesion. E-cadherin has significant roles in tissue development,
      adhesion between keratinocytes and retention of Langerhans cells in the
      epidermis, and its loss on tumour cells is frequently associated with metastasis.
      Here we describe a simple, flow cytometric adhesion assay to measure the effects
      of potential regulators of cell surface E-cadherin expression on E-cadherin
      mediated adhesion between cells. In this assay, cells that have been transiently
      transfected to express the protein of interest are enzymatically treated to
      remove cell surface E-cadherin. Cells are then incubated in low attachment
      plates, during which time the E-cadherin is re-expressed and E-cadherin-mediated
      aggregation occurs. The effect of the protein of interest on the percentage of E
      cadherin-mediated aggregates that form during incubation is measured flow
      cytometrically, following staining with an E-cadherin specific antibody. A major
      advantage of this assay is that a potential regulatory protein of interest can be
      tested in a transient expression system by co-expression with green fluorescent
      protein and analysis of adhesion conducted on green fluorescent cells only. We
      have applied this assay to measure the regulatory effects of E6 protein from
      human papillomavirus type 16 on E-cadherin-mediated adhesion but this assay
      potentially has broad applicability for testing the effects of other proteins on
      E-cadherin-mediated adhesion in an accurate and highly reproducible manner.

PMID- 15992816
TI  - Parameters affecting the display of antibodies on phage.
AB  - Despite the fact that a multitude of antibody phage display libraries has been
      built, systematic comparisons of critical design parameters are rare. Here we
      analysed the impact of various factors on the performance of the phage display
      system. First, we compared several vector designs for the display of Fab
      fragments of antibodies. Bicistronic as well as monocistronic expression of the
      antibody/pIII operon and vectors using fd-pIII as well as LC-pIII fusions were
      tested. Further, we evaluated the influence of glucose on the promoter induction.
      We compared monovalent versus oligovalent display of the antibody fragments and
      we used antibody fragments with different folding efficiency to assess the
      influence of the individual antibody sequences on the performance of the system.
      Finally, both phage display efficiency and yield of soluble Fab fragments were
      analysed. The significant differences found for phage yield, display of Fabs on
      the phage and expression of soluble Fabs suggest to use a bicistronic vector with
      an fd-fragment-pIII fusion for the construction of future Fab phage display
      libraries.

PMID- 15992815
TI  - Production of IgA monoclonal antibody against Shiga toxin binding subunits
      employing nasal-associated lymphoid tissue.
AB  - We established an IgA monoclonal antibody (mAb) against Shiga toxin 1 B subunits
      (Stx1B) from mouse nasal-associated lymphoid tissues (NALT) of BALB/c mice. We
      have developed an improved protocol in which cross-linked Stx1B is intranasally
      administered together with cholera toxin. Surface IgA-positive NALT lymphocytes
      from mice immunized in this manner were enriched and then fused with mouse
      myeloma cells to produce hybridoma cells. Hybridoma culture supernatants were
      examined to see if they contain IgA against Stx1B and if they can inhibit
      carbohydrate recognition by Stx1B. For the latter purpose, we prepared
      carbohydrate ligands in which globotriose is present on the poly-lysine backbone.
      The established IgA mAb exhibited saturable and dose-dependent binding to the
      immobilized Stx1B. Inversely, the binding of the carbohydrate ligands to the
      immobilized Stx1B was inhibited by the mAb pretreatment. Immunoblotting and SDS
      PAGE analysis revealed dimeric IgA. The IgA mAb inhibited the binding of
      digoxigenin-conjugated Stx1B to natural ligands displayed on a Burkitt's lymphoma
      cell line, Ramos. These results suggested that surface IgA-positive B cells in
      the inductive sites of the mucosal immune system in the upper respiratory tract
      are a potent source for producing IgA mAb against protein antigens with weak
      immunogenicity such as Stx1B.

PMID- 15992817
TI  - The duration of in vitro stimulation with recall antigens determines the subset
      distribution of interferon-gamma-producing lymphoid cells: a kinetic analysis
      using the Interferon-gamma Secretion Assay.
AB  - Analyses of cellular immune responses during natural infections and following
      vaccination with established or candidate vaccines are becoming increasingly
      important and so are the research tools used to achieve this goal. During a
      recent evaluation of the analytical performance characteristics of one of these
      techniques, the interferon-gamma secretion assay, we noticed that following
      overnight incubation of PBMC with recall antigens (varicella-zoster antigen,
      Candida albicans antigen or hepatitis B surface antigen) NK cells are frequently
      the most predominant interferon-gamma-producing cell population. In this study,
      we monitored the subset distribution of interferon-gamma-producing cells
      following more extended in vitro culture periods and found that, irrespective of
      the antigen applied, the contribution of NK cells decreased whereas the
      importance of T cells and NKT cells rose. Analysis of the subset distribution
      showed that HBsAg stimulated CD4 cells predominantly whereas Candida antigen and
      varicella-zoster antigen were better inducers of CD8 responses. No correlation
      was found between the kinetics of total number of interferon-gamma-producing
      cells and the changes of concentrations of interferon-gamma in the culture
      supernatants. Interferon-gamma levels in culture supernatants correlated strongly
      with the kinetics of T(H) lymphocytes (CD3+, CD4+), CTL (CD3+, CD8+), and NKT
      cells (CD3+, CD56+). These observations lead us to conclude that methods that
      enumerate cytokine-secreting cells without determining their phenotype should be
      interpreted with great care and that an 'elispot' should not be directly
      considered as the footprint of a T lymphocyte.

PMID- 15992818
TI  - Identification and characterization of antibodies that bind GPIIb/IIIa:
      antagonist complexes.
AB  - A potential limitation of anti-thrombotic therapies directed at platelet
      GPIIb/IIIa is immune mediated thrombocytopenia. Reagents that mimic the behavior
      of patient antibodies would provide a valuable tool for studies directed at
      understanding the basis of the immune mechanism involved in GPIIb/IIIa antagonist
      induced thrombocytopenia. Such reagents would bind epitopes that are exposed when
      the conformation of the receptor is modified in response to inhibitor binding. We
      describe the production and characterization of monoclonal antibodies that were
      raised against platelet GPIIb/IIIa bound to a potent antagonist, XP280. These
      antibodies have high affinity and specificity for XP280 bound GPIIb/IIIa using
      either purified protein or human platelets. We have demonstrated that the
      antibodies recognize a conformationally altered form of the receptor, that both
      subunits are required for binding, and that the antagonist itself does not form
      part of the binding epitope. Competition experiments indicate that multiple drug
      dependent epitopes are exposed on the receptor in response to antagonist binding.
      The antibodies bind with high specificity to some but not all GP
      IIb/IIIa/antagonist complexes indicating that different conformational epitopes
      are exposed when GP IIb/IIIa is bound to different antagonists.

PMID- 15992819
TI  - Spironolactone improves carotid artery fibrosis and distensibility in rat post
      ischaemic heart failure.
AB  - Myocardial infarction causes neurohormonal activation involving aldosterone and
      angiotensin II (AngII). These hormones may increase arterial stiffness, an
      independent cardiovascular risk factor contributing to progression of congestive
      heart failure (CHF). This study aimed to determine the effect of aldosterone and
      AngII blockade on carotid artery distensibility and collagen density in adult
      Wistar rats with MI-induced CHF. Five groups were studied: Sham-operated, CHF,
      CHF + spironolactone, CHF + lisinopril, CHF + Spironolactone + Lisinopril. After
      echocardiography, in vitro isobaric carotid distensibility (echo-tracking
      technique) and collagen density were measured, and the incremental elastic
      modulus (Einc) calculated. In the CHF group, intra-ventricular pressure and
      cardiac weight were increased; carotid distensibility was reduced (CHF: 0.42 +/-
      0.30 per mmHg(3) versus sham: 1.75 +/- 0.50 per mmHg(3); P < 0.001), and collagen
      content increased by 87% when compared to sham. All treatments reduced intra
      ventricular pressure, carotid distensibility and fibrosis when compared to CHF
      but did not change cardiac weight. However, carotid distensibility and intra
      ventricular pressure were not completely restored towards sham values and were
      significantly and inversely related. Spironolactone, which did not decrease
      significantly blood pressure, was the only drug reducing Einc independently of
      wall stress (WS). Thus, MI-induced CHF was associated with carotid artery
      remodeling. This vascular change, which may contribute to maintain cardiac
      hypertrophy and CHF, is largely prevented by AngII and aldosterone blockade. Only
      spironolactone reduced the stiffness of carotid wall material independently of
      blood pressure and WS.

PMID- 15992820
TI  - Signaling factors in stem cell-mediated repair of infarcted myocardium.
AB  - Myocardial infarction leads to scar formation and subsequent reduced cardiac
      performance. The ultimate therapy after myocardial infarction would pursue stem
      cell-based regeneration. The aim of stem cell-mediated cardiac repair embodies
      restoration of cardiac function by regeneration of healthy myocardial tissue,
      which is accomplished by neo-angiogenesis and cardiogenesis. A major reservoir of
      adult autologous stem cells distal from the heart is the bone marrow. Adequate
      regulation of signaling between the bone marrow, the peripheral circulation and
      the infarcted myocardium is important in orchestrating the process of
      mobilization, homing, incorporation, survival, proliferation and differentiation
      of stem cells, that leads to myocardial regeneration. In this review, we discuss
      key signaling factors, including cytokines, chemokines and growth factors, which
      are involved in orchestrating the stem cell driven repair process. We focus on
      signaling factors known for their mobilizing and chemotactic abilities (SDF-1, G
      CSF, SCF, IL-8, VEGF), signaling factors that are expressed after myocardial
      infarction involved in the patho-physiological healing process (TNF-alpha, IL-8,
      IL-10, HIF-1alpha, VEGF, G-CSF) and signaling factors that are involved in
      cardiogenesis and neo-angiogenesis (VEGF, EPO, TGF-beta, HGF, HIF-1alpha, IL-8).
      The future therapeutic application and capacity of secreted factors to modulate
      tissue repair after myocardial infarction relies on the intrinsic potency of
      factors and on the optimal localization and timing of a combination of signaling
      factors to stimulate stem cells in their niche to regenerate the infarcted heart.

PMID- 15992821
TI  - A structure-based model of the c-Myc/Bin1 protein interaction shows alternative
      splicing of Bin1 and c-Myc phosphorylation are key binding determinants.
AB  - The N terminus of the c-Myc oncoprotein interacts with Bin1, a ubiquitously
      expressed nucleocytoplasmic protein with features of a tumor suppressor. The c
      Myc/Bin1 interaction is dependent on the highly conserved Myc Box 1 (MB1)
      sequence of c-Myc. The c-Myc/Bin1 interaction has potential regulatory
      significance as c-Myc-mediated transformation and apoptosis can be modulated by
      the expression of Bin1. Multiple splicing of the Bin1 transcript results in
      ubiquitous, tissue-specific and tumor-specific populations of Bin1 proteins in
      vivo. We report on the structural features of the interaction between c-Myc and
      Bin1, and describe two mechanisms by which the binding of different Bin1 isoforms
      to c-Myc may be regulated in cells. Our findings identify a consensus class II
      SH3-binding motif in c-Myc and the C-terminal SH3 domain of Bin1 as the primary
      structure determinants of their interaction. We present biochemical and
      structural evidence that tumor-specific isoforms of Bin1 are precluded from
      interaction with c-Myc through an intramolecular polyproline-SH3 domain
      interaction that inhibits the Bin1 SH3 domain from binding to c-Myc. Furthermore,
      c-Myc/Bin1 interaction can be inhibited by phosphorylation of c-Myc at Ser62, a
      functionally important residue found within the c-Myc SH3-binding motif. Our data
      provide a structure-based model of the c-Myc/Bin1 interaction and suggest a mode
      of regulation that may be important for c-Myc function as a regulator of gene
      transcription.

PMID- 15992822
TI  - Mariner Mos1 transposase dimerizes prior to ITR binding.
AB  - The mariner Mos1 synaptic complex consists of a tetramer of transposase molecules
      that bring together the two ends of the element. Such an assembly requires at
      least two kinds of protein-protein interfaces. The first is involved in "cis"
      dimerization, and consists of transposase molecules bound side-by-side on a
      single DNA molecule. The second, which is involved in "trans" dimerization,
      consists of transposase molecules bound to two different DNA molecules. Here, we
      used biochemical and genetic methods to enhance the definition of the regions
      involved in cis and trans-dimerization in the mariner Mos1 transposase. The cis
      and trans-dimerization interfaces were both found within the first 143 amino acid
      residues of the protein. The cis-dimerization activity was mainly contained in
      amino acids 1-20. The region spanning from amino acid residues 116-143, and
      containing the WVPHEL motif, was involved in the cis- to trans-shift as well as
      in trans-dimerization stabilization. Although the transposase exists mainly as a
      monomer in solution, we provide evidence that the transposase cis-dimer is the
      active species in inverted terminal repeat (ITR) binding. We also observed that
      the catalytic domain of the mariner Mos1 transposase modulates efficient
      transposase-transposase interactions in the absence of the transposon ends.

PMID- 15992823
TI  - Effects of pH, salt, and macromolecular crowding on the stability of FK506
      binding protein: an integrated experimental and theoretical study.
AB  - Environmental variables can exert significant influences on the folding stability
      of a protein, and elucidating these influences provides insight on the
      determinants of protein stability. Here, experimental data on the stability of
      FKBP12 are reported for the effects of three environmental variables: pH, salt,
      and macromolecular crowding. In the pH range of 5-9, contribution to the pH
      dependence of the unfolding free energy from residual charge-charge interactions
      in the unfolded state was found to be negligible. The negligible contribution was
      attributed to the lack of sequentially nearest neighboring charged residues
      around groups that titrate in the pH range. KCl lowered the stability of FKBP12
      and the E31Q/D32N double mutant at small salt concentrations but raised stability
      after approximately 0.5 M salt. Such a turnover behavior was accounted for by the
      balance of two opposing types of protein-salt interactions: the Debye-Huckel
      type, modeling the response of the ions to protein charges, favors the unfolded
      state while the Kirkwood type, accounting for the disadvantage of the ions moving
      toward the low-dielectric protein cavity from the bulk solvent, disfavors the
      unfolded state. Ficoll 70 as a crowding agent was found to have a modest effect
      on protein stability, in qualitative agreement with a simple model suggesting
      that the folded and unfolded states are nearly equally adversely affected by
      macromolecular crowding. For any environmental variable, it is the balance of its
      effects on the folded and unfolded states that determines the outcome on the
      folding stability.

PMID- 15992824
TI  - Inactivation of the mitochondrial heat shock protein zim17 leads to aggregation
      of matrix hsp70s followed by pleiotropic effects on morphology and protein
      biogenesis.
AB  - The biogenesis of mitochondrial matrix proteins involves the translocase of the
      outer membrane, the presequence translocase of the inner membrane and the
      presequence translocase-associated motor. The mitochondrial heat shock protein 70
      (mtHsp70) forms the central core of the motor. Recent studies led to the
      identification of Zim17, a mitochondrial zinc finger motif protein that interacts
      with mtHsp70. Different views have been reported on the localization of Zim17 in
      the mitochondrial inner membrane or matrix. Depletion of Zim17 impairs several
      critical mitochondrial processes, leading to inhibition of protein import,
      defects of Fe/S protein biogenesis and aggregation of Hsp70s in the matrix.
      Additionally, we found that inactivation of Zim17 altered the morphology of
      mitochondria. These pleiotropic effects raise the question of the specific
      function of Zim17 in mitochondria. Here, we report that Zim17 is a heat shock
      protein of the mitochondrial matrix that is loosely associated with the inner
      membrane. To address the function of Zim17 in organello, we generated a
      temperature-sensitive mutant allele of the ZIM17 gene in yeast. Upon a short-term
      shift of the yeast mutant cells to a non-permissive temperature, matrix Hsp70s
      aggregated while protein import, Fe/S protein activity and mitochondrial
      morphology were not, or only mildly, affected. Only after a long-term shift to
      non-permissive temperature, were strong defects in protein import, Fe/S protein
      activity and mitochondrial morphology observed. These findings suggest that the
      heat shock protein Zim17 plays a specific role in preventing protein aggregation
      in the mitochondrial matrix, and that aggregation of Hsp70s causes pleiotropic
      effects on protein biogenesis and mitochondrial morphology.

PMID- 15992825
TI  - The N-terminal cleavable extension of plant carrier proteins is responsible for
      efficient insertion into the inner mitochondrial membrane.
AB  - A subset of mitochondrial carrier proteins from plants contain a cleavable N
      terminal extension. We have used a reconstituted protein import assay system into
      intermembrane space-depleted mitochondria to study the role of the cleavable
      extension in the carrier import pathway. Insertion of carrier proteins into the
      inner membrane can be stimulated by the addition of a soluble intermembrane space
      fraction isolated from plant mitochondria. Greater stimulation of import of the
      adenine nucleotide carrier (ANT) and phosphate carrier (Pic), which contain N
      terminal cleavable extensions, was observed compared to the import of the
      oxoglutarate malate carrier (OMT), which does not contain a cleavable extension.
      Removal of the N-terminal cleavable extension from ANT and Pic resulted in loss
      of stimulation of insertion into the inner membrane. Conversely, addition of the
      N-terminal extension from ANT or Pic to OMT resulted in significantly enhanced
      insertion into the inner membrane. The polytopic inner membrane proteins TIM17
      and TIM23 that are imported via the carrier import pathway contain no cleavable
      extension, displayed high-level stimulation of insertion into the inner membrane
      by addition of the intermembrane space fraction. Addition of the N-terminal
      cleavable extension from carrier proteins to TIM23 enhanced insertion of TIM23
      into the inner membrane even in the absence of the soluble intermembrane space
      fraction. Together, these results demonstrate that the cleavable N-terminal
      extensions present on carrier proteins from plants are required for efficient
      insertion into the inner mitochondrial membrane, and that they can stimulate
      insertion of any carrier-like protein into the inner membrane.

PMID- 15992826
TI  - Angiotensin II exerts positive feedback on the intrarenal renin-angiotensin
      system by an angiotensin converting enzyme-dependent mechanism.
AB  - BACKGROUND: Plasma angiotensin II (ANG II) is not increased significantly in
      renovascular hypertension (RVH), but tissue ANG II levels are elevated in both
      kidneys of renovascular rats. Because the contralateral, non-ischemic kidney is
      critical for maintenance of hypertension in RVH, this study sought to understand
      the mechanism by which intrarenal ANG II levels are augmented in the non-ischemic
      kidney. This study tested the hypothesis that an incremental increase in plasma
      ANG II induces the intrarenal renin-angiotensin system (RAS) in the non-ischemic
      kidney by an angiotensin converting enzyme (ACE) dependent mechanism. METHODS: To
      simulate the incremental increase in plasma ANG II induced by the ischemic kidney
      in RVH, an ANG II infusion model was used. This model used a chronic infusion of
      ANG II (40 ng/min) or vehicle by osmotic minipump into uninephrectomized rats.
      Parallel groups were treated with the ACE inhibitor Enalaprilat (200 mg/kg/day).
      Intrarenal ACE activity was measured by radioenzymatic assay. ANG II levels were
      quantified by radioimmunoassay. RESULTS: Hypertension was evident in ANG II
      infused rats, compared to control rats (155 +/- 4 versus 112 +/- 1 mmHg; P <
      0.001). Concurrent treatment with Enalaprilat reversed the hypertension induced
      by ANG II infusion (98 +/- 3 versus 155 +/- 4 mmHg; P < 0.001). ANG II up
      regulated intrarenal ACE activity in the non-ischemic kidney (59.2 +/- 11.9
      versus 25.2 +/- 6.8 units/mg protein; P < 0.01). Enalaprilat significantly
      decreased renal ACE activity in ANG II-treated rats, compared to ANG II alone
      (11.4 +/- 1.0 versus 59.2 +/- 11.9 units/mg protein; P < 0.001). Intrarenal ANG
      II was increased in ANG II-infused rats, compared to control animals (52.9 +/-
      7.1 versus 23.0 +/- 3.2 fmol/mg tissue; P < 0.001), and Enalaprilat prevented ANG
      II-induced increases in intrarenal ANG II (29.9 +/- 2.6 versus 52.9 +/- 7.1
      fmol/mg tissue; P < 0.05). CONCLUSION: Incremental changes in plasma ANG II
      induce de novo production of ANG II in the non-ischemic kidney to augment
      intrarenal ANG II content. ACE inhibition blocks this positive feedback loop,
      suggesting that ANG II activates the intrarenal RAS by an ACE-dependent
      mechanism. The impact of ACE inhibition on blood pressure suggests that this
      feedback loop may be an important mechanism for maintenance of hypertension in
      RVH.

PMID- 15992827
TI  - Decreased beta-amyloid peptide42 in cerebrospinal fluid of patients with
      progressive supranuclear palsy and corticobasal degeneration.
AB  - Several previous studies have identified biochemical markers for Alzheimer's
      disease (AD): cerebrospinal fluid (CSF)-beta-amyloid peptide42 (CSF-Abeta42), CSF
      total tau protein (CSF-tau) and CSF-phosphorylated tau protein (CSF-ptau).
      Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) as well
      as AD are diseases with tauopathies. CSF-Abeta42, CSF-tau, and CSF-ptau have not
      been rigorously investigated in PSP and CBD. In the present study, we assessed
      CSF-Abeta42, CSF-tau, and CSF-ptau as biochemical markers for PSP and CBD,
      compared with AD. The subjects consisted of 18 cases of PSP, 9 cases with CBD, 69
      cases with AD, and 43 control subjects. Genotyping or phenotyping of
      apolipoprotein E (apoE) was also performed. CSF-Abeta42 levels were significantly
      decreased in patients with PSP and CBD as well as in AD patients. The ratio of
      CSF-ptau to CSF-Abeta42 provided high diagnostic accuracy to distinguish both PSP
      from AD, and CBD from AD. ApoE genotype/phenotype was not associated with CSF
      Abeta42 levels in all groups. We concluded that CSF-Abeta42 levels are reduced in
      PSP and CBD as well as in AD.

PMID- 15992828
TI  - Retrograde degeneration of the corticospinal tract associated with pontine
      infarction.
AB  - We report a 40-year-old man with myotonic dystrophy who survived for 5 years
      after pontine infarction. Serial MRI detected abnormal T2 elongation of the
      corticospinal tract at the cerebral peduncle 4 years after the infarction. An
      autopsy confirmed the existence of retrograde degeneration extending from the
      pons to the internal capsule, evidence that retrograde degeneration in the
      corticospinal tract occurs above the pontine level. MRI was suggested to be
      useful for detection of the degenerative process.

PMID- 15992829
TI  - Dejerine-Sottas syndrome and vestibular loss due to a point mutation in the PMP22
      gene.
AB  - We describe a father and daughter with Dejerine-Sottas syndrome and bilateral
      vestibular loss due to an L71P missense mutation in the peripheral myelin protein
      22 (PMP22). The combination of vestibular loss and peripheral neuropathy led to
      profound imbalance at a young age. It is important to recognize this combination
      of peripheral nerve and vestibular deficits since rehabilitation strategies and
      prognosis are different.

PMID- 15992830
TI  - Cellular diagnostics and coral health: declining coral health in the Florida
      Keys.
AB  - Coral reefs within the Florida Keys are disappearing at an alarming rate. Coral
      cover in the Florida Keys National Marine Sanctuary declined by 38% from 1996 to
      2000. In 2000, populations of Montastraea annularis at four sites near Molasses
      Reef within the Florida Keys National Marine Sanctuary and one reef within
      Biscayne National Park were sampled on a quarterly basis. Anecdotal observations
      showed corals at Alina's Reef in Biscayne National Park appeared healthy in
      March, but experienced an acute loss of coral cover by August. Cellular
      Diagnostic analysis indicated that Alina's Reef corals were in distress: they had
      been afflicted with a severe oxidative damaging and protein-denaturing stress
      that affected both the corals and their symbiotic zooxanthellae. This condition
      was associated with a significant xenobiotic detoxification response in both
      species, reflecting probable chemical contaminant exposure. These results
      demonstrate that applying a Cellular Diagnostic approach can be effective in
      helping to identify stress and its underlying causes, providing diagnostic and
      prognostic biomarkers of coral health.

PMID- 15992831
TI  - Sediment quality survey of the Choctawhatchee Bay system in the Florida
      panhandle.

PMID- 15992832
TI  - A multivariate assessment of coastal eutrophication. Examples from the Gulf of
      Finland, northern Baltic Sea.
AB  - The Gulf of Finland is the sub-basin of the Baltic Sea that is most seriously
      affected by the effects and consequences of eutrophication. In this study,
      physical, chemical and biological long-term data (1980-2002) from the Finnish
      environmental monitoring programme is used to detect possible gradients of
      eutrophication in the Gulf. The Finnish coastal area of the Gulf of Finland is
      divided into three parts in an east-west direction, and into three zones (inner,
      middle, outer) according to differences in descriptive parameters. We use
      principal component analysis (PCA) to study spatial and temporal differences in
      relation to eutrophication. Clear differences between coastal and offshore areas
      are seen. Differences between eastern and western Gulf are not as evident. The
      changes due to eutrophication are larger for the inner archipelago, whereas the
      outer areas have been more stable over time. The concentration of oxygen is the
      strongest driving factor for eutrophication in the region.

PMID- 15992833
TI  - Modulation of signal transduction by tea catechins and related phytochemicals.
AB  - Epidemiologic studies in human populations and experimental studies in rodents
      provide evidence that green tea and its constituents can inhibit both the
      development and growth of tumors at a variety of tissue sites. In addition, EGCG,
      a major biologically active component of green tea, inhibits growth and induces
      apoptosis in a variety of cancer cell lines. The purpose of this paper is to
      review evidence that these effects are mediated, at least in part, through
      inhibition of the activity of specific receptor tyrosine kinases (RTKs) and
      related downstream pathways of signal transduction. We also review evidence
      indicating that the antitumor effects of the related polyphenolic phytochemicals
      resveratrol, genistein, curcumin, and capsaicin are exerted via similar
      mechanisms. Some of these agents (EGCG, genistein, and curcumin) appear to
      directly target specific RTKs, and all of these compounds cause inhibition of the
      activity of the transcription factors AP-1 and NF-kappaB, thus inhibiting cell
      proliferation and enhancing apoptosis. Critical areas of future investigation
      include: (1) identification of the direct molecular target(s) of EGCG and related
      polyphenolic compounds in cells; (2) the in vivo metabolism and bioavailability
      of these compounds; (3) the ancillary effects of these compounds on tumor-stromal
      interactions; (4) the development of synergistic combinations with other
      antitumor agents to enhance efficacy in cancer prevention and therapy, and also
      minimize potential toxicities.

PMID- 15992834
TI  - The oxidative neurotoxicity of clioquinol.
AB  - Clioquinol is a metal chelator that may attenuate beta-amyloid deposition and
      mitigate the progression of Alzheimer's disease. Its prior use as a systemic
      antibiotic was associated with a neurodegenerative syndrome, subacute myelo
      optico-neuropathy (SMON), although a mechanistic link has not been precisely
      defined. While testing clioquinol in murine cortical cultures, it was observed to
      have a pro-oxidant effect. Exposure to 1-3 microM for 24 h increased
      malondialdehyde, and resulted in death of approximately 40% of neurons; a higher
      concentration (30 microM) was paradoxically less toxic. Both malondialdehyde
      production and cell death were attenuated by concomitant treatment with the
      antioxidants ascorbic acid and Trolox C, or with the lipid-soluble metal chelator
      1,10-phenanthroline. In contrast, injury was increased in cultures prepared from
      mice lacking heme oxygenase-2, which protects against non-heme mediated oxidative
      injury to neurons. Addition of vitamin B12 to the culture medium was not
      cytoprotective. These results suggest that therapeutically relevant
      concentrations of clioquinol are toxic to cultured neurons by an oxidative
      mechanism that is unrelated to vitamin B12 deficiency. In vivo evaluation of the
      pro-oxidant effect of clioquinol seems warranted prior to further clinical
      trials.

PMID- 15992836
TI  - Water intake during the development of renal hypertension (2K-1C) in mice.
AB  - For both practical and methodological reasons, mice have been the most widely
      employed species for development of transgenic and gene knockin and knockout
      animals. However, basic behavioral and physiology control and regulatory
      mechanisms in mice are not well characterized. To broaden our understanding of
      the processes maintaining body fluid and blood pressure homeostasis in the mouse,
      the objectives of this study were to evaluate voluntary water, and sodium intakes
      during the development of renal hypertension and to examine the relationship
      between hypertension and the quantities of water and salt ingested. In male,
      C57BL/6J mice, two-kidney, one-clip renal hypertension (2K-1C) was induced, and
      water and 1.8% NaCl intakes were monitored for 2 weeks. At the end of this
      period, all animals received arterial catheters for direct recording of blood
      pressure. The mice that received renal artery clips were sorted into hypertensive
      (152+/-4 mm Hg) and normotensive (122+/-2 mm Hg) groups and were compared to
      control (117+/-4 mm Hg) animals that underwent a sham renal clipping procedure.
      Hypertensive 2K-1C animals had significantly elevated water intake compared to
      control animals. On most of the postsurgical days, the normotensive 2K-1C animals
      did not display increased water intake in comparison to the control group. No
      significant effect was detected for 1.8% saline intake between any of the pairs
      of groups. In summary, the reduction of blood flow to a single kidney in the 2K
      1C model of renal hypertension induces high blood pressure accompanied by
      sustained hyperdipsia in the mouse.

PMID- 15992835
TI  - Reduced auditory M100 asymmetry in schizophrenia and dyslexia: applying a
      developmental instability approach to assess atypical brain asymmetry.
AB  - Although atypical structural and functional superior temporal gyrus (STG)
      asymmetries are frequently observed in patients with schizophrenia and
      individuals with dyslexia, their significance is unclear. One possibility is that
      atypical asymmetries reflect a general risk factor that can be seen across
      multiple neurodevelopmental conditions--a risk factor whose origins are best
      understood in the context of Developmental Instability (DI) theory. DI measures
      (minor physical anomalies (MPAs) and fluctuating asymmetries (FAs)) reflect
      perturbation of the genetic plan. The present study sought to assess whether the
      presence of peripheral indices of DI predicts anomalous functional auditory
      cortex asymmetry in schizophrenia patients and dyslexia subjects. The location of
      the auditory M100 response was used as a measure of functional STG asymmetry, as
      it has been reported that in controls (but not in subjects with schizophrenia or
      dyslexia) the M100 source location in the right hemisphere is shifted anterior to
      that seen for the left hemisphere. Whole-brain auditory evoked magnetic field
      data were successfully recorded from 14 male schizophrenia patients, 21 male
      subjects with dyslexia, and 16 normal male control subjects. MPA and FA measures
      were also obtained. Replicating previous studies, both schizophrenia and dyslexia
      groups showed less M100 asymmetry than did controls. Schizophrenia and dyslexia
      subjects also had higher MPA scores than normal controls. Although neither total
      MPA nor FA measures predicted M100 asymmetry, analyses on individual MPA items
      revealed a relationship between high palate and M100 asymmetry. Findings suggest
      that M100 positional asymmetry is not a diagnostically specific feature in
      several neurodevelopmental conditions. Continued research examining DI and brain
      asymmetry relationships is warranted.

PMID- 15992837
TI  - Recruitment pattern of muscle fibre type during high intensity exercise (60-100%
      VO2max) in thoroughbred horses.
AB  - To consider the optimal training programme for Thoroughbred horses, we examined
      the recruitment pattern of muscle fibres including hybrid muscle fibres in well
      trained Thoroughbred horses. The horses performed exercise at three different
      intensities and durations; i.e., 100% VO2max for 4 min, 80% and 60% VO2max for 8
      min on a treadmill with 10% incline. Muscle samples were obtained from the middle
      gluteal muscle before, during (4 min at 80% and 60% VO2max), and after exercise.
      Four muscle fibre types (types I, IIA, IIA/IIX, and IIX) were
      immunohistochemically identified, and optical density of periodic acid Schiff
      staining (OD-PAS) in each fibre type, and the glycogen content of the muscle
      sample, were determined by quantitative histochemical and biochemical procedures.
      The changes in OD-PAS showed that the recruitment of all fibre types were
      identical at the final time stage of each exercise bout, i.e., 4 min running at
      100% VO2max, and 8 min running at 80% and 60% VO2max. The changes in OD-PAS of
      type IIA/IIX fibre were very similar to those of type IIX fibre. The recruitment
      of these fibres were obviously more facilitated by 4 min running at 100% VO2max
      than by 4 min running at 80% or 60% VO2max. Short duration with high intensity
      exercise, such as 4 min running at 100% VO2max or 8 min running at 80% or 60%
      VO2max, is effective to stimulate type IIX fibre and IIA/IIX fibres that have the
      fastest speed of contraction.

PMID- 15992838
TI  - Giardiasis as a predictor of childhood malnutrition in Orang Asli children in
      Malaysia.
AB  - A cross-sectional study to examine the association of giardiasis with protein
      energy malnutrition, vitamin A deficiency and iron deficiency anaemia was
      conducted among Orang Asli children in Selangor, Malaysia. A total of 281
      children aged 2-15 years were studied. The data were collected using structured
      questionnaires, anthropometric measurements and laboratory analysis of blood and
      faecal samples. The results showed that 24.9% of the children were infected with
      Giardia duodenalis, while 56.5, 61.3 and 15.1% had significant underweight,
      stunting and wasting, respectively. Giardiasis was statistically identified as a
      strong predictor of significant wasting in this study population.

PMID- 15992839
TI  - Financial costs of deworming children in all primary schools in Cambodia.
AB  - In 2002, Cambodia's Ministry of Health launched a deworming programme to deliver
      an anthelmintic drug (mebendazole 500 mg) and health education to 75% of its
      school children twice a year. Cambodia's school population is approximately 2.8
      million. The deworming programme was organized into two phases: the first phase
      (December 2002-March 2003) targeted more than one million school children from 11
      provinces; and the second phase (July 2003-January 2004) targeted the entire
      school population. The cost to treat each child was 12 cents (0.11 USD) during
      the first phase, 6 cents during the second phase, and 3 cents for re-treatment in
      areas where the campaign was conducted for the second time. The Cambodian
      experience demonstrates that, with political commitment, high coverage for
      deworming is achievable even in a country with minimal resources. Cambodia's
      deworming programme represents a successful model for other developing countries.

PMID- 15992840
TI  - Alveolar macrophages have a dual role in a rat model for trimellitic anhydride
      induced occupational asthma.
AB  - Occupational exposure to low molecular weight chemicals, like trimellitic
      anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs)
      are among the first cells to encounter inhaled compounds. These cells can produce
      many different mediators that have a putative role in asthma. In this study, we
      examined the role of AMs in lung function and airway inflammation of rats exposed
      to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or
      received vehicle alone on days 0 and 7. One day before challenge, rats received
      intratracheally either empty or clodronate-containing liposomes to deplete the
      lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air.
      Lung function parameters were measured before, during, within 1 h after, and 24 h
      after challenge. IgE levels and parameters of inflammation and tissue damage were
      assessed 24 h after challenge. Sensitization with TMA led to decreased lung
      function parameters during and within 1 h after challenge as compared to non
      sensitized rats. AM depletion alleviated the TMA-induced drop in lung function
      parameters and induced a faster recovery compared to sham-depleted TMA-sensitized
      rats. It also decreased the levels of serum IgE 24 h after challenge, but did not
      affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue
      TNF-alpha levels. In contrast, AM depletion augmented the TMA-induced tissue
      damage and inflammation 24 h after challenge. AMs seem to have a dual role in
      this model for TMA-induced occupational asthma since they potentiate the
      immediate TMA-induced decrease in lung function but tended to dampen the TMA
      induced inflammatory reaction 24 h later.

PMID- 15992841
TI  - Microbial cell wall agents as an occupational hazard.
AB  - Organic dusts cause inflammatory reactions in the tissues exposed. The lung and
      the cells lining the surface of the respiratory tract are a primary target. Many
      receptors have been shown to react specifically on the presence of microorganisms
      that are ubiquitous elements in organic dusts. There is a great variability in
      the individual response to organic dusts. Almost 50% of Caucasians are
      hyporesponders to LPS exposure, and people with alpha-1-antitrypsin deficiency
      are hyperresponsive to organic dust exposure. The diseases resulting from organic
      dust exposures include asthma, allergy, hypersensitivity pneumonitis and toxic
      pneumonitis (organic dust toxic syndrome). This paper deals with inflammation and
      the subsequent mechanism of disease as it is encountered in industries with these
      exposures. Toxicological studies including human experimental exposures and ex
      vivo studies of cells are described. Cellular reactions are mediated through the
      attachment of, e.g. LPS and beta (1,3)-D-glucan to lipopolysaccharide binding
      protein, CD14 and Toll-like receptors. The relation between protein release and
      the gene activation is described. Furthermore, studies of the individual
      susceptibility will be reviewed.

PMID- 15992842
TI  - DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and
      immunotoxicity.
AB  - 1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations
      (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters
      (hematological and of humoral immunity) were studied in styrene-exposed human
      subjects and controls. Results were correlated with genetic polymorphisms in DNA
      repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3,
      exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity
      after stratification for the different DNA repair genetic polymorphisms showed
      that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal
      and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest
      levels of biomarkers were associated with the wild-type homozygous AA genotype.
      The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited
      the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin
      D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the
      analyzed subjects. The number of eosinophiles was positively associated with XPD
      variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC
      variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an
      XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P <
      0.05). Both C3- and C4-complement components were lower in individuals with XRCC3
      CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and
      sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility
      may be reflected in genotoxic and immunotoxic responses to environmental and
      occupational exposures to xenobiotics.

PMID- 15992843
TI  - Low level exposure to chemicals and immune system.
AB  - Industrialized countries are facing an increase of diseases attributable to an
      alteration of the immune system function, and concern is growing that this trend
      could be at least partially attributable to new and modified patterns of exposure
      to chemicals. Among chemicals matter of concern, pesticides can be included. The
      Authors have reviewed the existing evidence of pesticide immunotoxicity in
      humans, showing that existing data are inadequate to raise conclusions on the
      immunotoxic risk related to these compounds. The limits of existing studies are:
      poor knowledge on exposure levels, heterogeneity of the approach, and difficulty
      in giving a prognostic significance to the slight changes often observed. To
      overcome these limits, the Authors have proposed a tier approach, based on three
      steps: the first, addressed at pointing out a possible immunomodulation; the
      second, at refining the results and the third one, when needed, to finalize the
      study and to point out concordance with previous results. Studies should
      preferably be carried out through comparison of pre- and post-exposure findings
      in the same groups of subjects to be examined immediately after the end of the
      exposure. A simplification of the first step approach can be used by the
      occupational health physician and the occupational toxicologist. Conclusions on
      the prognostic significance of the slight changes often observed will be reached
      only by validating the hypothesis generated by field studies with an
      epidemiological approach. In this field, the most useful option is represented by
      longitudinal perspective studies.

PMID- 15992844
TI  - Medically assisted reproduction and ethical challenges.
AB  - Many of the ethical challenges associated with medically assisted reproduction
      are societal. Should the technique be restricted to only ordinary couples or
      could it be used also to single females or couples of same sex? Should the future
      child be entitled to know the identity of the gamete donor? Should there be age
      limits? Can embryos or gametes be used after the death of the donor? Can
      surrogate mothers be part of the process? Can preimplantation diagnostics be used
      to select the future baby's sex? In addition, there are several clearly medical
      questions that lead to difficult ethical problems. Is it safe to use very
      premature eggs or sperms? Is the risk for some rare syndromes caused by
      imprinting errors really increased when using these techniques? Do we transfer
      genetic infertility to the offspring? Is the risk for multiple pregnancies too
      high when several embryos are implanted? Does preimplantation diagnosis cause
      some extra risks for the future child? Should the counselling of these couples
      include information of all these potential but unlikely risks? The legislation
      and practices differ in different countries and ethical discussion and
      professional guidelines are still needed.

PMID- 15992845
TI  - Complementary gene and protein expression studies and integrative approaches in
      toxicogenomics.
AB  - Parallel transcript and protein profiling is a strategy to gain further insight
      into the mechanisms of toxicity and disease. The technologies used to measure
      expression at the transcript and protein levels each convey different information
      and have different technical capabilities that can complement each other when
      combined. In this review, over twenty studies are considered for the use of 
      Omics platform, the chemical or disease being profiled, tissues, the number of
      genes and proteins found by each platform and common expression products. A
      strategy is suggested for toxicant expression profiling that combines the
      transcriptomics and proteomics of both the target tissue and blood/serum that
      could provide a more complete characterization of toxicity as well as synergize
      expression technologies toward biomarker discovery.

PMID- 15992846
TI  - Rosmarinic acid, a new snake venom phospholipase A2 inhibitor from Cordia
      verbenacea (Boraginaceae): antiserum action potentiation and molecular
      interaction.
AB  - Many plants are used in traditional medicine as active agents against various
      effects induced by snakebite. The methanolic extract from Cordia verbenacea (Cv)
      significantly inhibited paw edema induced by Bothrops jararacussu snake venom and
      by its main basic phospholipase A2 homologs, namely bothropstoxins I and II
      (BthTXs). The active component was isolated by chromatography on Sephadex LH-20
      and by RP-HPLC on a C18 column and identified as rosmarinic acid (Cv-RA).
      Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid [2
      O-cafeoil-3-(3,4-di-hydroxy-phenyl)-R-lactic acid]. This is the first report of
      RA in the species C. verbenacea ('baleeira', 'whaler') and of its anti
      inflammatory and antimyotoxic properties against snake venoms and isolated
      toxins. RA inhibited the edema and myotoxic activity induced by the basic PLA2s
      BthTX-I and BthTX-II. It was, however, less efficient to inhibit the PLA2
      activity of BthTX-II and, still less, the PLA2 and edema-inducing activities of
      the acidic isoform BthA-I-PLA2 from the same venom, showing therefore a higher
      inhibitory activity upon basic PLA2s. RA also inhibited most of the myotoxic and
      partially the edema-inducing effects of both basic PLA2s, thus reinforcing the
      idea of dissociation between the catalytic and pharmacological domains. The pure
      compound potentiated the ability of the commercial equine polyvalent antivenom in
      neutralizing lethal and myotoxic effects of the crude venom and of isolated PLA2s
      in experimental models. CD data presented here suggest that, after binding, no
      significant conformation changes occur either in the Cv-RA or in the target PLA2.
      A possible model for the interaction of rosmarinic acid with Lys49-PLA2 BthTX-I
      is proposed.

PMID- 15992847
TI  - A methodology for structural health monitoring with diffuse ultrasonic waves in
      the presence of temperature variations.
AB  - Diffuse ultrasonic waves for structural health monitoring offer the advantages of
      simplicity of signal generation and reception, sensitivity to damage, and large
      area coverage; however, there are the serious disadvantages of no accepted
      methodology for analyzing the complex recorded signals and sensitivity to
      environmental changes such as temperature and surface conditions. Presented here
      is a methodology for applying diffuse ultrasonic waves to the problem of
      detecting structural damage in the presence of unmeasured temperature changes.
      This methodology is based upon the prediction and observation that the first
      order effect of a temperature change on a diffuse ultrasonic wave is a time
      dilation or compression. A multi-step procedure is implemented to (1) record a
      set of baseline waveforms from the undamaged specimen at temperatures spanning
      the expected operating range, (2) select a waveform from the baseline set whose
      temperature is the closest to that of a subsequently measured signal, (3) adjust
      this baseline waveform to best match the signal, and (4) calculate an error
      parameter between the signal and the adjusted waveform and compare this parameter
      to a threshold to determine the structural status. This procedure is applied to
      experimental data from aluminum plate specimens with artificial flaws.
      Probability of detection and the minimum flaw size detected are presented as a
      function of the size of the baseline waveform set. It is shown that a probability
      of detection of over 95% can be achieved with a small number of baseline
      waveforms.

PMID- 15992848
TI  - Characterization of plasma membrane-associated proteins from Aedes albopictus
      mosquito (C6/36) cells that mediate West Nile virus binding and infection.
AB  - This study isolated and characterized the West Nile virus (WNV) putative receptor
      molecule(s) from Aedes albopictus mosquito (C6/36) cells. The binding of WNV to
      C6/36 cells was saturated with 5000 particles per cell. The entry of WNV into
      C6/36 cells was strongly inhibited when pretreated with proteinase K and to a
      lesser extent with sodium periodate. However, pretreatment of C6/36 cells with
      phospholipases, glycosidases, heparinases and neurimidase had no effect on virus
      entry. By using virus overlay protein blot assay, WNV was observed to bind to the
      140-kDa, 95-kDa, 70-kDa and 55-kDa plasma membrane-associated molecules isolated
      from C6/36 cells. Murine antibodies generated against the 95-kDa and 70-kDa
      membrane proteins effectively blocked WNV, Japanese encephalitis virus (JEV) and
      Dengue virus (DV) serotype 2 infection in C6/36 cells. In addition, the binding
      of the recombinant-WNV envelope domain III protein to C6/36 cells can be
      inhibited by the anti-95-kDa and anti-70-kDa membrane protein antibodies. These
      data strongly supported the possibility that the 95-kDa and 70-kDa plasma
      membrane-associated proteins are part of a receptor complex for mosquito-borne
      flaviviruses (WNV, JEV and DV) on mosquito cells.

PMID- 15992849
TI  - Use of alternate coreceptors on primary cells by two HIV-1 isolates.
AB  - Two HIV-1 isolates (CM4 and CM9) able to use alternate HIV-1 coreceptors on
      transfected cell lines were tested for their sensitivity to inhibitors of HIV-1
      entry on primary cells. CM4 was able to use CCR5 and Bob/GPR15 efficiently in
      transfected cells. The R5 isolate grew in Delta32/Delta32 CCR5 PBMC in the
      absence or presence of AMD3100, a CXCR4-specific inhibitor, indicating that it
      uses a receptor other than CCR5 or CXCR4 on primary cells. It was insensitive to
      the CCR5 entry inhibitors RANTES and PRO140, but was partially inhibited by vMIP
      1, a chemokine that binds CCR3, CCR8, GPR15 and CXCR6. The coreceptor used by
      this isolate on primary cells is currently unknown. CM9 used CCR5, CXCR4,
      Bob/GPR15, CXCR6, CCR3, and CCR8 on transfected cells and was able to replicate
      in the absence or presence of AMD3100 in Delta32/Delta32 CCR5 PBMC. It was
      insensitive to eotaxin, vMIP-1 and I309 when tested individually, but was
      inhibited completely when vMIP-1 or I309 was combined with AMD3100. Both I309 and
      vMIP-1 bind CCR8, strongly suggesting that this isolate can use CCR8 on primary
      cells. Collectively, these data suggest that some HIV-1 isolates can use
      alternate coreceptors on primary cells, which may have implications for
      strategies that aim to block viral entry.

PMID- 15992850
TI  - Mutations increasing exposure of a receptor binding site epitope in the soluble
      and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope
      glycoprotein.
AB  - The caprine arthritis-encephalitis (CAEV) and ovine maedi-visna (MVV) viruses are
      resistant to antibody neutralization, a feature shared with all other
      lentiviruses. Whether the CAEV gp135 receptor binding site(s) (RBS) in the
      functional surface envelope glycoprotein (Env) is protected from antibody
      binding, allowing the virus to resist neutralization, is not known. Two CAEV
      gp135 regions were identified by extrapolating a gp135 structural model that
      could affect binding of antibodies to the RBS: the V1 region and a short sequence
      analogous in position to the human immunodeficiency virus type 1 gp120 loop B
      postulated to be located between two major domains of CAEV gp135. Mutation of
      isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity
      of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7
      299 which recognizes an epitope overlapping the gp135 RBS. The I166A mutation
      also stabilized or exposed the F7-299 epitope in anionic detergent buffers,
      indicating that the I166A mutation induces conformational changes and stabilizes
      the RBS of soluble gp135 and enhances Mab F7-299 binding. In contrast, the
      affinity of a V1 deletion mutant of gp135 for the receptor and Mab F7-299 and its
      structural stability did not differ from that of the wild-type gp135. However,
      both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell
      fusion activity and binding of Mab F7-299 to the oligomeric Env. Therefore, the
      CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent
      and independent of Env oligomerization which are disrupted by the V1 deletion and
      the I166A mutation, respectively. In addition, we found a correlation between
      side-chain beta-branching at amino acid position 166 and binding of Mab F7-299 to
      oligomeric Env and cell-to-cell fusion, suggesting local secondary structure
      constraints in the region around isoleucine-166 as one determinant of gp135 RBS
      exposure and antibody binding.

PMID- 15992851
TI  - Oral immunization with pBsVP6-transgenic alfalfa protects mice against rotavirus
      infection.
AB  - A critical factor in edible plant-derived vaccine development is adequate
      expression of the exogenous antigens in transgenic plants. We synthesized a codon
      optimized gene (sVP6) encoding the VP6 protein of human group A rotavirus and
      inserted it into the alfalfa genome using agrobacterium-mediated transformation.
      As much as 0.28% of the total soluble protein of the pBsVP6-transgenic alfalfa
      was sVP6. Female BALB/c mice were gavaged weekly with 10 mg of transgenic alfalfa
      extract containing 24 microg of sVP6 protein and 10 microg of CpG-rich
      oligodeoxynucleotides as mucosal adjuvant. Immunized mice developed high titers
      of anti-VP6 serum IgG and mucosal IgA. Offspring of immunized dams developed less
      severe diarrhea after challenge with simian rotavirus SA-11, indicating that
      antibodies generated in the dams provided passive heterotypic protection to the
      pups. These results suggest that oral immunization with pBsVP6-transgenic alfalfa
      provides a potential means of protecting children and young animals from severe
      acute rotavirus-induced diarrhea.

PMID- 15992852
TI  - Effect of river water, sediment and time on the toxicity and bioavailability of
      molinate to the marine bacterium Vibrio fischeri (Microtox).
AB  - The toxicity and bioavailability of molinate to Vibrio fischeri (Microtox((R)))
      were determined in both laboratory and river water in the absence and presence of
      sediment after 0, 24, 48, 72 and 96-h exposure. The bioavailability of molinate,
      expressed as 5min EC50s (bioluminescence) and their fiducial limits calculated
      using initial measured concentrations, to V. fischeri in laboratory water in the
      absence and presence of sediment ranged from 1.8 (1.7-2.1) to 3.6 (3.5-3.7) mgL(
      1) and 1.3 (1.2-1.4) to 4.2 (3.5-4.5) mgL(-1), respectively. The corresponding
      values in river water and river water plus sediment were 1.7 (1.6-1.8) to 3.8
      (3.6-4.1) and 1.3 (1.3-1.4) to 4.6 (4.2-4.9) mgL(-1), respectively. River water
      did not significantly (P>0.05) reduce the bioavailability of molinate to V.
      fischeri compared to that of laboratory water. However, the presence of sediment
      significantly (P<0.05) reduced the bioavailability of molinate to V. fischeri in
      both waters. The exposure time also significantly (P<0.05) reduced the
      bioavailability of molinate to V. fischeri in both waters in the presence and
      absence of sediment. The type of water did not significantly (P>0.05) affect the
      loss of molinate during the 96-h exposure period. However, the presence of
      sediment significantly (P<0.01) increased the loss of molinate from the test
      solutions, probably by binding to the sediment particles. Exposure period and
      concentration levels significantly (P<0.05) affected the loss of the herbicides
      over the 96h.

PMID- 15992853
TI  - Destruction of cresols by Fenton oxidation process.
AB  - The present study was used to probe the treatment of simulated wastewater
      containing cresols by Fenton process. Experiments were conducted in a batch
      reactor to examine the effects of operating variables like pH, hydrogen peroxide
      concentration (H(2)O(2)) and ferrous ion concentration (Fe(2+)) on chemical
      oxygen demand (COD) removal. The progress of the degradation reaction was
      monitored by the decrease in COD content in the treated solution. The optimal
      reacting conditions were experimentally determined and it was found to be
      [H(2)O(2)]=31.64 mM, [Fe(2+)]=0.90 mM for o- and p-cresol while 0.72 mM for m
      cresol at pH=3.0+/-0.2. The degradation efficiency for cresol isomers was as high
      as 82% within 120 min at optimum conditions. A pseudo-first-order kinetic model
      was adopted to represent the Fenton oxidation for cresols. The mineralization
      rate for cresols obeys the following sequence: m->p->o-. Maximum degradation
      occurred at 30 degrees C for the temperature range of 20-50 degrees C studied.
      The global activation energy for the first-order reaction was estimated to be in
      the range of 12.90-16.25 kJ/mol. Air/nitrogen did not play an active role in
      completely mineralizing the organic intermediates at the experimental conditions
      adopted. Irrespective of the position of methyl group in o-, m- or p-position,
      the maximum dissolved organic carbon (DOC) removal efficiency was 42%. Only 2/5th
      of cresol was mineralized to CO(2) by Fenton process. The results showed that the
      cresols were completely oxidized and degraded into lower molecular weight
      aliphatic acids. Among the acids, acetic and oxalic acids were identified as the
      major products formed during the degradation.

PMID- 15992854
TI  - Sorption studies of Zn(II) and Cu(II) onto vegetal compost used on reactive
      mixtures for in situ treatment of acid mine drainage.
AB  - The efficiency of the sulphate reducing bacteria-based in situ treatment of acid
      mine drainage is often limited by the low degradability of the current carbon
      sources, typically complex plant-derived materials. In such non-sulphate-reducing
      conditions, field and laboratory experiences have shown that mechanisms other
      than sulphide precipitation should be considered in the metal removal, i.e. metal
      (oxy)hydroxides precipitation, co-precipitation with these precipitates, and
      sorption onto the organic matter. The focus of the present paper was to present
      some laboratory data highlighting the Zn and Cu sorption on vegetal compost and
      to develop a general and simple model for the prediction of their distribution in
      organic-based passive remediation systems. The model considers two kinds of
      sorption sites ( succeeds SO(2)H(2)) and the existence of monodentate and
      bidentate metal-binding reactions, and it assumes that only free M(2+) species
      can sorb onto the compost surface. The acid-base properties of the compost were
      studied by means of potentiometric titrations in order to identify the nature of
      the involved surface functional groups and their density. The distribution
      coefficient (K(D)) for both Zn and Cu were determined from batch experiments as a
      function of pH and metal concentration. The model yielded the predominant surface
      complexes at the experimental conditions, being succeeds SO(2)Zn for Zn and
      succeeds SO(2)HCu(+) and ( succeeds SO(2)H)(2)Cu for Cu, with log K(M) values of 
      2.10, 3.36 and 4.65, respectively. The results presented in this study have
      demonstrated that the proposed model provides a good description of the sorption
      process of Zn and Cu onto the vegetal compost used in these experiments.

PMID- 15992855
TI  - Effect of cadmium on growth, ultramorphology of leaf and secondary metabolites of
      Phyllanthus amarus Schum. and Thonn.
AB  - The pollution is increasing in the environment by different kinds of human
      activities, which results in the accumulation of heavy metals including cadmium
      in the soil and water and it causes different types of problems to living beings.
      As the plants are utilized by human being as food and medicine, therefore, it is
      mandatory to see the effect of metals on plants. In this context, efforts have
      been made to observe the effect of different concentration of Cadmium (Cd) on
      Phyllanthus amarus Schum. and Thonn., because Cd is the widespread metal and the
      plants response to low and high level of exposure is a complex phenomenon. P.
      amarus is mostly grown as weed in agricultural and waste lands. It is a reputed
      plant used in Indian indigenous systems of medicine with hepatoprotective,
      diuretic, stomachic properties and is recently being used for the treatment of
      hepatitis B. The study revealed that Cd causes significant decrease in fresh and
      dry weight, length of root and shoot, protein, chlorophyll, carotenoids and sugar
      and increase in starch content. It is interesting to note that the
      therapeutically active compounds-phyllanthin and hypophyllanthin, enhanced at
      certain levels of Cd due to abiotic stress. Besides, the ultramorpholical changes
      were also observed in stomatal opening and wax deposition on both the surfaces of
      leaves.

PMID- 15992856
TI  - Structure-based classification of active and inactive estrogenic compounds by
      decision tree, LVQ and kNN methods.
AB  - The performance of decision tree (DT), learning vector quantization (LVQ), and k
      nearest neighbour (kNN) methods classifying active and inactive estrogenic
      compounds in terms of their structure activity relationship (SAR) was evaluated.
      A set of 311 compounds was used for construction of the models, the predictive
      power of which was verified with separate training and test sets. Principal
      components derived from molecular descriptors calculated with DRAGON software
      were used as variables representing the structures of the compounds. Broadly, kNN
      had the best classification ability and DT the weakest, although the performance
      of each method was dependent on the group of compounds used for modelling. The
      best performance was obtained with kNN for the calf estrogen receptor data,
      averaging 98.3% of correctly classified compounds in the external tests. Overall,
      the results indicate that all the methods tested are suitable for the SAR
      classification of estrogenic compounds, producing models with a predictive power
      ranging from adequate to excellent.

PMID- 15992857
TI  - A computationally feasible quantum chemical model for 13C NMR chemical shifts of
      PCB-derived carboxylic acids.
AB  - Two quantum chemical models have been derived for the prediction of 13C NMR
      chemical shifts of novel PCB acids obtained from PCBs by catalytic carbonylation.
      13C isotropic shielding constants were calculated employing the GIAO (gauge
      independent atomic orbital) method with density functional theory (DFT). The best
      results were obtained by cluster calculations, which took the solvent effects
      into account properly. In this approach, a solvent molecule (acetone) was
      attached by a hydrogen bond to every hydrogen atom present in a PCB acid, and the
      geometry of the molecular cluster was optimized employing the AM1 method. For 158
      chemical shifts, the cross-validated standard error was 2.8 ppm and the cross
      validated correlation coefficient was 0.94.

PMID- 15992858
TI  - Seasonal distribution and contamination levels of total PHCs, PAHs and heavy
      metals in coastal waters of the Alang-Sosiya ship scrapping yard, Gulf of Cambay,
      India.
AB  - Alang-Sosiya situated on the Gulf of Cambay is one of the largest ship breaking
      yard in the world. The seasonal distribution and contamination levels of
      dissolved and/or dispersed total petroleum hydrocarbons (PHCs), total polycyclic
      aromatic hydrocarbons (PAHs) and heavy metals in seawater during high tide are
      investigated. The concentrations of petroleum hydrocarbons and heavy metals are
      higher in the winter than in the monsoon and summer. The concentrations of total
      PHCs and PAHs are about three times higher in the winter and two times in the
      monsoon or summer at Along-Sosiya and about twice in all seasons at two stations
      one on either side 5 km away from it as compared to the reference station at
      Mahuva, 60 km away towards the south. Further, the levels of PHCs are correlated
      with salinity and compared with those of other regions. The concentration of all
      metals is the highest in the winter season followed by the monsoon and summer. We
      carried out the quantitative analysis of the possible relationships among 13
      variables such as Al, Fe, Pb, Mn, Cu, Zn, Cd, Cr, Co, pH, NO3-, NO2 and PO4(3-).

PMID- 15992859
TI  - A preliminary assessment of consumer's exposure to pesticide residues in
      fisheries products.
AB  - The fisheries products in this study comprise fish, bivalve, crustacean and
      cephalopod collected from different types of markets in Taiwan between the years
      2001 and 2003. A total of 91 pesticide residues belonging to four major pesticide
      groups were tested and analyzed. The test results show that 65.40% of fish,
      93.55% of shellfish, 84.92% of crustacean and 98.33% of cephalopod samples
      contain no detectable residues. There are only two kinds (organochlorine and
      organophosphate) of totally six pesticides (DDTs, dieldrin, chlorpyrifos,
      fenitrotion, fenthion and prothion) that have been detected from the fisheries
      products in this study. For there were pesticides present in the fish products,
      consumption of fisheries product there was no zero risk. But the exposure of
      consumer did not exceed the acceptable daily intakes (ADI). For male, there was
      the highest risk in exposure to dieldrin, which the percentage of ADI was 93.56%.
      This study also suggests that a yearly monitoring program for organophosphate
      pesticide residues in fish is necessity.

PMID- 15992860
TI  - Halogenated compounds in a dated sediment core of the Teltow Canal, Berlin: time
      related sediment contamination.
AB  - To study the recent contamination history of DDT (1,1,1-trichloro-2,2
      bis(chlorophenyl)ethane) and its metabolites, as well as methoxychlor (1,1,1
      trichloro-2,2-bis(p-methoxyphenyl)ethane), chlorfenson (4-chlorophenyl-p
      chlorobenzenesulfonate), and further halogenated aromatics, a sediment core was
      collected from the Teltow Canal in Berlin (Germany). The sampling site is located
      nearby a former industrial point source, where recently analyses on pre-samples
      have indicated high concentrations of halogenated organic compounds. The
      deposition time of the investigated sediments was determined by gamma
      spectrometrical dating. Pollution trends of selected contaminants were attributed
      to a time period between 5 and 10 years. Concentration profiles reflect not only
      the recent pollution history of these compounds, but also the time-depending
      effects of the ban, restriction and termination of DDT-production in the German
      Democratic Republic (GDR). DDT and other chlorinated aromatic compounds were
      produced onsite until the late 1980s. Maximum values of 133 mg kg(-1) (dry
      weight) for p,p'-DDD (1,1-dichloro-2,2-bis(chlorophenyl)ethane) and approximately
      100 mg kg(-1) (dry weight) for p,p'-DDMS (1-chloro-2,2-bis(chlorophenyl)ethane),
      main metabolites of the anaerobic degradation of DDT, were determined. The
      occurrence of all selected contaminants, most of which have been banned more than
      10 years ago, demonstrate recent contamination pathways, and the necessity of a
      continuous long-term monitoring of the affected environment.

PMID- 15992861
TI  - Distribution of polychlorinated dibenzo-p-dioxins and dibenzofurans in suspended
      sediments, dissolved phase and bottom sediment in the Houston Ship Channel.
AB  - Spatial distributions of polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs) in the water column and bottom sediments of the Houston
      Ship Channel in Texas were measured three times over a 1-year period. Total TEQ
      concentrations in water ranged from 0.01 to 0.25 pg/l for the dissolved phase and
      from 0.09 to 2.91 pg/l for the suspended phase, while TEQ concentrations in
      bottom sediments varied from 0.9 to 139.8 ng/kg dry wt. The dissolved
      concentrations were lower than their respective suspended concentrations, with
      average dissolved/suspended ratios between 0.11 and 0.59 for individual
      congeners. More than 89% of the total concentration of 2378-substituted
      PCDD/PCDFs was attributable to OCDD but 2378-TCDD was the major contributor to
      total TEQ for the three sampled media. Average logs of organic carbon-normalized
      suspended sediment-dissolved partitioning coefficients (logK(oc)(obs)) varied
      between 4.92 and 8.59 l/kg-oc; while in the bottom sediment-dissolved interface,
      logK(oc)(obs) values ranged from 5.48 to 8.48 l/kg-oc. Observed logK(oc)values
      varied within a factor of 0.64-1.26 from equilibrium logK(oc) values, suggesting
      fluxes of PCDD/PCDFs across the interfaces. It was found that in the HSC, on
      average, the tendency of a compound to move from the particulate phase to the
      dissolved phase decreases with increasing K(ow).

PMID- 15992862
TI  - Oreopithecus: still apelike after all these years.

PMID- 15992863
TI  - Life span is related to the free energy of mitochondrial DNA.
AB  - Broadly speaking, the mitochondrial theory of aging relates aging to the rate of
      damage to mitochondria. In this work, I concentrate on a DNA sequence property,
      the free energy, which can be interpreted as a factor in the susceptibility of
      mitochondrial DNA (mtDNA) to mutation. I show that life spans across a broad
      range of species are a function of the mtDNA free energy and are proportional to
      the probability of opening of bubbles of single-stranded mtDNA of approximately
      20 base pairs in length, in agreement with the measured nucleation size of these
      bubbles. These transient separations of the mtDNA strands are a possible aging
      mechanism, through increased mtDNA mutations. In comparisons of species with
      similar life spans, avian mtDNA has more negative free energy than does mammalian
      mtDNA, suppressing the predicted probability of mtDNA bubble formation in birds
      by over 80% and thus protecting them against mutation. Based on these results I
      propose three hypotheses about the conflicting evolutionary forces that have
      acted on the free energy of mtDNA.

PMID- 15992864
TI  - Ecological restoration of mineland with particular reference to the metalliferous
      mine wasteland in China: A review of research and practice.
AB  - Despite a principal contributor to the rapid economic growth, the mining industry
      in China produced a large amount of wasteland and caused water pollution and soil
      erosion as well as other environmental damages. In 2002, this industry generated
      265.4 Mt tailings, 130.4 Mt gangue and 107.8 Mt smelting slags. The degraded land
      associated with mining is estimated to be 3.2 Mha by the end of 2004,
      deteriorating the land shortage of China. Restoration of mine wasteland began in
      late 1970s but the restoration process was sluggish. The overall restoration rate
      (the ratio of reclaimed land area to the total degraded land area) of mine
      wasteland was some 10-12% with a higher rate for coal mine spoils but a lower
      rate for metal-mined derelict land. From 1994 to 2004, 149 research papers were
      published about the restoration of China's mining wasteland, of which 70 were on
      metal-mined land and 61 on the non-metal-mined land. Although 37 institutions in
      China were involved in the restoration research, only a few remained active and
      productive. Metal-mined derelict land is often more metal toxic and deficient of
      macronutrients and is tougher for revegetation. Many substrate amelioration
      techniques were proposed and tolerant plant species were tested for use of
      reclamation of the metal-mined tailings. Five hyperaccumulator species have been
      reported in China for the potential use in phytoremediation. However, these
      accomplishments were all at laboratory or small-scale field demonstration stage
      and still far from the practical use in reality. To accelerate the restoration
      and utilization of mine wasteland, several recommendations are put forward in
      this review. Above these suggestions, the commitment and efficiency of the
      government at all levels are vital.

PMID- 15992865
TI  - Particle size distribution and atmospheric metals measurements in a rural area in
      the South Eastern USA.
AB  - Atmospheric particle mass concentrations were measured at a site adjacent to Lake
      Hartwell, GA, during six dry sampling events in February-March 2003. The overall
      average PM2.5 mass concentration was 9.5 microg/m3 and the overall average total
      suspended particles mass concentration was 19.1 microg/m3. Particulate matter was
      collected on a deposition plate mounted onto a specially designed wind vane and
      was subsequently analyzed to determine the particle size distribution. The
      average geometric particle diameter was found to be 2.8 microm. Particulate
      matter collected was found to be closely approximately at log-normal
      distribution, with a count median diameter of 1.5 mum and a geometric standard
      deviation of 1.8. Individual metal concentrations present in airborne particulate
      matter were determined for cadmium, chromium, copper, iron, lead, manganese,
      nickel, and zinc using inductively coupled plasma-mass spectrometry analysis of
      samples collected on Teflon filters. Ambient metal concentrations were found to
      range from 0.8 ng/m3 for cadmium to 512 ng/m3 for iron. The dry deposition flux
      of metals was estimated to be in the range of 0.17 mg/(m2 year) for cadmium to
      102 mg/(m2 year) for iron. More samples need to be collected and analyzed, both
      temporally and spatially, in order to establish atmospheric metals fluxes onto
      surfaces.

PMID- 15992866
TI  - Acute pulmonary embolism in childhood.
AB  - Pulmonary embolism is an uncommon, but potentially fatal disease in children.
      Most children with pulmonary embolism have underlying clinical conditions, of
      which the presence of a central venous catheter is the most frequent. The
      clinical presentation is often subtle, or masked by the underlying clinical
      condition. Diagnostic as well as therapeutic strategies for pulmonary embolism in
      children are mostly extrapolated from studies in adults. Pulmonary angiography is
      still the gold standard in diagnosing pulmonary embolism, but several other
      radiographic tests can be used to diagnose pulmonary embolism, including
      ventilation-perfusion lung scanning, helical computed tomography, magnetic
      resonance imaging and echocardiography. The choice of treatment depends on the
      clinical presentation of the patient. Anticoagulation is the mainstay of therapy
      for children with pulmonary embolism. However, thrombolytic therapy can be
      considered for patients with hemodynamic instability. The outcome of pediatric
      pulmonary embolism is uncertain and needs to be studied.

PMID- 15992867
TI  - A collaborative study to establish a Korea national biological standard for
      antithrombin concentrate.
AB  - BACKGROUND AND OBJECTIVES: Six laboratories consisting of three manufacturers and
      three national control laboratories participated in a collaborative study to
      evaluate the suitability of a candidate material to serve as the first Korean
      National Standard for Antithrombin (AT) concentrate. MATERIALS AND METHODS: The
      potency of this candidate preparation was determined using the heparin cofactor
      chromogenic method. The method is described in the Minimum Requirements for
      Biological Products in Korea and in the European Pharmacopoeia. The candidate was
      calibrated against the second International Standard for AT concentrate, coded as
      96/520. RESULTS: The participants contributed data from a total of 90 independent
      assays and the results were accepted as statistically valid when the outcome of
      the analysis exhibited linear dose-response relationships and intersected at a
      common point at zero dose in the slope-ratio model. The combined potency
      estimates were obtained by taking the geometric means of results from all assays
      at each laboratory, and overall potency estimates were calculated as unweighted
      geometric means of results from all laboratories. The results were expressed in
      the form of histograms with 95% confidence intervals. CONCLUSIONS: According to
      the results of the collaborative study, the candidate preparation showed
      excellent intra- and inter-laboratory correlations and is judged to be suitable
      to serve as the Korean National Standard for AT concentrate with the following
      potency: 51.9 IU/vial (95% confidence intervals=48.24 approximately 55.98
      IU/vial).

PMID- 15992868
TI  - Which factors predict upper urinary tract deterioration in overactive neurogenic
      bladder dysfunction?
AB  - OBJECTIVES: To determine whether bladder histopathologic changes, detrusor leak
      point pressure (DLPP), disease duration, and preoperative catheterization time
      can predict for upper urinary tract (UUT) deterioration in patients with
      overactive neurogenic bladder dysfunction (ONBD). METHODS: A total of 39 patients
      (7 women and 32 men) with ONBD who were treated with augmentation cystoplasty
      were included in the study. The patients had undergone perioperative full
      thickness bladder biopsies during augmentation cystoplasty. Routine evaluation
      using light microscopy to investigate for inflammation, fibrosis, and mast cell
      count was done. Statistical analysis was done using the chi-square and Mann
      Whitney U tests. RESULTS: The mean duration of the disease was 8.7 years. Of the
      39 patients, 18 (46%) had had indwelling catheters preoperatively. UUT
      deterioration was found in 16 (41%) of 39 patients. The mean DLPP was 105 cm H2O.
      The severity of detrusor fibrosis was a significant risk factor for UUT
      deterioration (P = 0.036). However, the degree of inflammation and the severity
      of fibrosis did not affect UUT deterioration. A DLPP of more than 75 cm H2O was a
      statistically significant risk factor (P = 0.04), but the disease duration and
      preoperative catheterization time were not. CONCLUSIONS: The results of our study
      have shown that moderate to severe fibrosis in the detrusor and a DLPP of more
      than 75 cm H2O are the risk factors for UUT deterioration in patients with ONBD.
      However, additional studies, including ones with more patients, are needed to
      determine the relationship between the histopathologic changes and UUT
      deterioration in ONBD.

PMID- 15992869
TI  - Clinical effects of suburothelial injection of botulinum A toxin on patients with
      nonneurogenic detrusor overactivity refractory to anticholinergics.
AB  - OBJECTIVES: To investigate the clinical and urodynamic effects of suburothelial
      injection of botulinum A toxin on patients with nonneurogenic detrusor
      overactivity. Intradetrusor injection of botulinum A toxin has been used to treat
      patients with detrusor overactivity. Suburothelial injection of botulinum A toxin
      might effectively inhibit the occurrence of detrusor overactivity mediated by
      sensory nerves. METHODS: Twenty patients with nonneurogenic detrusor overactivity
      refractory to anticholinergics were enrolled and treated with injection of 200 U
      botulinum A toxin into the suburothelial space. The clinical effects on the lower
      urinary tract symptoms and urodynamic parameters were assessed. RESULTS: At 3
      months after treatment, 9 patients had regained continence (45%), 8 had
      improvement (40%), and treatment had failed in 3 (15%). At 6 months after
      treatment, 7 patients remained continent, but treatment had failed in 5.
      Hematuria developed in 1 patient, urinary tract infection in 7 (35%), and a large
      postvoid residual urine volume requiring catheterization in 6 (30%). Hesitancy in
      initiation and difficult urination was also noted in 15 patients (75%). The
      volume of the first sensation of bladder filling and bladder capacity increased
      about two times; however, the voiding efficiency was reduced by 50% at 2 weeks
      after treatment. The postvoid residual urine volume was increased by seven times
      the baseline value at 2 weeks and had decreased to three times greater at 3 and 6
      months after treatment. CONCLUSIONS: The results of this study have shown that
      suburothelial injection of 200 U botulinum A toxin impairs bladder sensation and
      voiding efficiency, but is effective in the treatment of nonneurogenic detrusor
      overactivity. Transient urinary retention and the development of urinary tract
      infection should be carefully monitored.

PMID- 15992870
TI  - Prostate cryotherapy: more questions than answers.

PMID- 15992871
TI  - Prevalence and impact on generic quality of life of urinary incontinence in
      Japanese working women: assessment by ICI questionnaire and SF-36 Health Survey.
AB  - OBJECTIVES: To examine the prevalence of urinary incontinence (UI) and the
      relationship between UI and generic quality of life (QOL) in working women.
      METHODS: Of 7229 female hospital nurses in Japan, 3734 (51.7%) responded to a
      self-administered postal questionnaire that included the Rand Medical Outcomes
      Study 36-item Health Survey (SF-36) and the International Consultation on
      Incontinence questionnaire (ICIQ) for evaluating symptoms and health-related QOL.
      RESULTS: The overall prevalence of UI in Japanese working women aged 20 to 64
      years (mean 35.2) was 16.7%. The main type of incontinence was stress UI (73%).
      Its prevalence increased with age and reached a plateau at age 45 to 49 years
      (34.7%). The ICIQ score also correlated significantly with age. Generic QOL,
      especially physical functioning, role-physical, social functioning, and role
      emotional, was significantly impaired by UI. A comparison of subjects with and
      without UI revealed that the differences in the physical and mental component
      summary scores of the SF-36 were largest in the age groups of 25 to 29 and 55 to
      59 years, respectively. The correlations of the ICIQ score with the physical and
      mental component scores were most significant in the age groups of 25 to 29 and
      45 to 49 years, respectively. The impact of mixed UI on QOL showed a greater
      tendency than that of stress or urge UI. CONCLUSIONS: The prevalence of UI showed
      an age-related increase, with a peak at 45 to 49 years old. The impact of UI on
      physical health was great in individuals in their 20s, but its impact on mental
      health increased in the older age groups.

PMID- 15992872
TI  - Botulinum-A toxin for treatment of overactive bladder without detrusor
      overactivity: urodynamic outcome and patient satisfaction.
AB  - OBJECTIVES: To investigate the effect of botulinum toxin type A bladder
      injections in the treatment of overactive bladder syndrome in the absence of
      detrusor overactivity. METHODS: The subjects were 7 women (average age 61.1
      years, range 51 to 79) who presented with overactive bladder symptoms. Their
      disorder had been refractory to several classic treatment options. Urodynamic
      examination excluded detrusor overactivity. A total of 300 U BTX-A (Botox) was
      injected, of which 50 to 75 U was injected as quadrant injections into the
      external sphincter muscle to avoid the postoperative need for catheterization in
      the case of high postvoid residual urine volume. For follow-up, complete
      urodynamic studies were performed, and a bladder diary and validated incontinence
      questionnaires were given to patients at all visits at 1, 3, and 6 months.
      RESULTS: The bladder diaries indicated a clear reduction in daytime frequency and
      nocturia and a reduction in pad use. The maximal voiding volume increased
      significantly. The urodynamic examinations showed a significant increase in
      volume when the first and the strong desire to void were expressed. The maximal
      bladder capacity increased by 20% in 3 months. In the questionnaires, 5 of the 7
      patients reported better urine control after therapy, and 6 would have chosen
      this therapy again for their condition. The overall satisfaction score (on a
      scale of 0 to 10) averaged 6.8. No side effects, such as urine retention,
      occurred. CONCLUSIONS: Botulinum-A toxin injection has positive effects in
      treating overactive bladder symptoms without detrusor overactivity. The effects
      were seen not only in urodynamic measures but also in patient satisfaction.

PMID- 15992873
TI  - Efficacy of functional electrical stimulation-biofeedback with sexual cognitive
      behavioral therapy as treatment of vaginismus.
AB  - OBJECTIVES: To report 12 cases of vaginismus that were successfully treated with
      functional electrical stimulation (FES)-biofeedback with sexual cognitive
      behavioral therapy (SCBT) to determine the efficacy of FES-biofeedback with SCBT
      as a standard therapy for vaginismus. Vaginismus is an involuntary spasm of the
      musculature of the outer third of the vagina that leads to impossible vaginal
      penetration, causing personal distress. Various therapeutic approaches, both
      physiologic and psychological, have been considered. METHODS: Twelve women with
      vaginismus referred from a checkup outpatient clinic participated in this study.
      The patients enrolled in this study had vaginismus according to the criteria of
      the Diagnostic and Statistical Manual of Mental Disorders. The patients were
      assessed before and after treatment with gynecologic examinations and structured
      interviews pertaining to sexual function and psychological adjustment. After the
      diagnosis of vaginismus, we conducted weekly pelvic floor muscle relaxation using
      FES-biofeedback. Once the patients became tolerable to vaginal manipulation, the
      eight-stage SCBT (eight-stage gradual desensitization described by Kaplan using
      vaginal self-dilation with fingers and vaginal probe insertion) was added for 8
      weeks. RESULTS: After 8 weeks of treatment, all 12 couples had completed the
      program, had become tolerable to vaginal insertion of larger size probes, and
      could achieve satisfactory vaginal intercourse. CONCLUSIONS: FES-biofeedback with
      SCBT is an effective aid for patients with vaginismus to learn muscle control.
      Therefore, it may increase the success rate of treatment of vaginismus.

PMID- 15992874
TI  - Tolerability and morbidity of urodynamic testing: a questionnaire-based study.
AB  - OBJECTIVES: To determine the tolerability and morbidity rate of multichannel
      urodynamics (UDS). METHODS: A total of 154 consecutive patients were included in
      the present study; 87 men and 67 women underwent UDS and completed a
      questionnaire. All patients undergoing UDS were given a two-part questionnaire.
      The first part, given immediately after UDS, contained four questions regarding
      pain, embarrassment, and physical burden (assessed with a visual analogue scale
      on which 0 = not at all, 10 = unbearable), as well as willingness to undergo UDS
      again. The second part, given within 2 weeks after UDS, contained five questions
      regarding micturition pain, gross hematuria, dysuria, cloudy urine, and fever
      episodes after UDS. Urine specimens were also analyzed. RESULTS: The mean (+/-SD)
      degrees of pain, embarrassment, and physical burden were 2.27 +/- 2.53, 2.59 +/-
      2.69, and 1.76 +/- 2.43, respectively, and 73.6% of men and 80.6% of women were
      willing to repeat UDS. The most common complaint after UDS was micturition pain.
      Two men and 1 woman had fever after UDS; there was no relationship between fever
      and urinary tract infections. Urinalysis showed that 4.6% of men and 7.5% of
      women had leukocyturia after the investigation. CONCLUSIONS: The complication
      rates of UDS were relatively low. For most patients, UDS were tolerable and
      acceptable. Proper informed consent is necessary.

PMID- 15992875
TI  - Quality of life and disease severity in Korean women with stress urinary
      incontinence.
AB  - OBJECTIVES: To evaluate whether disease severity influences quality of life using
      the Incontinence Quality of Life questionnaire and to determine the factors that
      effectively reflect disease severity in women with stress urinary incontinence
      (SUI). METHODS: A total of 109 women (mean age 54.9 years, range 31 to 77) with
      UI were included in the primary analyses. Data from the responses to the
      Incontinence Quality of Life questionnaires, 1-hour pad testing, uroflowmetry,
      postvoid residual urine volume measurements, and videourodynamic study were
      included for analysis. Of the 109 patients, 24 (22.0%) were mildly, 53 (48.6%),
      moderately, and 32 (29.4%) severely affected, respectively, as determined by self
      perceived severity. RESULTS: The Incontinence Quality of Life total scores were
      associated with several variables, including self-perceived disease severity (P <
      0.001), type of UI (P = 0.009), number of UI episodes (P = 0.022), association
      with no specific activity (P = 0.017), and maximal flow rate (P = 0.027).
      Multiple linear regression analysis showed that self-reported disease severity (P
      < 0.001) was a potential risk factor of a poorer quality of life. The perceived
      severity of UI increased with stress pad weight (P = 0.010) and the number of UI
      episodes (P = 0.005). CONCLUSIONS: These findings suggest that self-perceived
      disease severity significantly influences the quality of life of patients with
      SUI. Although UI episodes or the number of pads used have been routinely used to
      evaluate SUI severity, strategies for assessing SUI should also incorporate self
      perceived disease severity.

PMID- 15992876
TI  - Correlation of office-based cystoscopy and cytology with histologic diagnosis:
      how good is the reference standard?
AB  - OBJECTIVES: To evaluate the accuracy of cystoscopy and cytology in predicting the
      histopathologic features of suspicious cystoscopic lesions. METHODS: We reviewed
      the bladder biopsy records at two institutions from July 2001 to July 2004.
      Intraoperative biopsies were performed for positive (papillary or sessile) (n =
      155) and equivocal (n = 101) lesions found during office cystoscopy. The
      specimens were submitted for histopathologic analysis, and the results were
      correlated with the preceding office-based cystoscopy and cytology findings.
      RESULTS: Malignancy was found in 27 (26.7%) of 101 equivocal lesions and 128
      (82.5%) of 155 sessile or papillary lesions. Of the 72 biopsies performed for
      equivocal lesions in patients with a history of transitional cell carcinoma
      (TCC), 24 (33%) had malignancy compared with 3 (10.3%) of 29 biopsies performed
      in patients without a history of TCC. For patients with no history of TCC and
      equivocal lesions, cytology was able to identify all neoplasms (100% sensitivity)
      and negative cytology always predicted a normal biopsy result (100% negative
      predictive value). However, for patients with a history of TCC and equivocal
      lesions, cytology had a sensitivity and negative predictive value of 81.8% and
      88.2%, respectively. CONCLUSIONS: Our findings suggest that patients without a
      history of TCC who have an equivocal lesion at cystoscopy may avoid an
      unnecessary operation if they have normal cytology findings. A large number of
      patients with equivocal cystoscopic findings undergo unnecessary biopsies in the
      operating room, and future studies should be performed to assess the value of
      other bladder markers in predicting oncologic status in this setting.

PMID- 15992877
TI  - Current management of transplant renal artery stenosis: clinical utility of
      duplex Doppler ultrasonography.
AB  - OBJECTIVES: To perform a retrospective study to determine the clinical utility of
      Doppler ultrasonography (DUS) and to determine its role in the management of
      transplant renal artery stenosis (TRAS). METHODS: Patients undergoing DUS between
      January 1998 and January 2001 for clinical suspicion of TRAS were included in the
      study. A total of 51 patients were divided into two groups according to the peak
      systolic velocity. Additional management was based on the clinical and DUS
      findings and their congruence. Patients were followed up and their outcome was
      analyzed. RESULTS: Of the 51 patients who entered the study, 26 were in the low
      probability group (LPG) and 25 in the high probability group (HPG). Nine patients
      in the LPG underwent additional investigations; eight underwent magnetic
      resonance angiography and one angiography. Of these 9 patients, 6 had stenosis, 4
      of whom required angiography. In total, 5 patients from the LPG underwent
      angioplasty, and 4 of them had stenosis (1 with TRAS, 2 with common iliac artery
      stenosis, and 1 with renal artery ostial stenosis). Three patients underwent
      angioplasty and 2 of them improved. In the HPG, 20 of 25 patients underwent
      additional investigations, including magnetic resonance angiography in 12 and
      angiography in 8, with stenosis in 15 patients. Of the HPG, 13 of 25 patients
      underwent angiography, with 10 requiring angioplasty--8 for TRAS and 2 for
      adjacent renal artery stenosis, with improvement in 8 patients. Congruent
      clinical and DUS findings were highly predictive of significant stenosis more
      amenable to improvement. CONCLUSIONS: The results of our study have shown that
      high-probability DUS and congruent clinical findings are likely to identify a
      significant stenosis that is amenable to treatment. Low-probability DUS findings
      do not eliminate the possibility of stenosis, but intervention in this group is
      less likely to result in improvement.

PMID- 15992878
TI  - Randomized comparison of standard laparoscopic trainer to novel, at-home, low
      cost, camera-less laparoscopic trainer.
AB  - OBJECTIVES: To evaluate the utility of a portable, at-home, low-cost, camera-less
      laparoscopic trainer to provide laparoscopy training inexpensively and outside
      the constraints of the hospital environment. METHODS: Twenty-two urology
      residents (postgraduate year 1 to 7) were tested prospectively on four basic
      laparoscopic tasks on a standard video laparoscopic trainer (pretest). Objective
      and subjective data were collected for each participant. The subjects were then
      randomized to 5 hours of training on either a portable, camera-less trainer
      (group 1) or a standard video laparoscopic trainer (group 2). Each resident was
      then retested on the initial same four laparoscopic tasks (post-test). Efficiency
      ratios were calculated for each task, incorporating both time and accuracy.
      Improvements between the pretest and post-test evaluations were compared between
      the two groups using the two-group t test. RESULTS: All subjects significantly
      improved their performance with training. The average improvement in the time
      required to complete the laparoscopic tasks for all participants was 36%.
      Efficiency increased by 52%. However, no difference was found between the two
      groups. In the poststudy self-evaluations, 91% of participants in group 1 either
      agreed or strongly agreed that the at-home trainer was a helpful teaching
      modality. CONCLUSIONS: The improvements in laparoscopic skills on our
      inexpensive, portable, at-home, camera-less trainer were not significantly
      different from those gained using a traditional video laparoscopic trainer.
      Participants trained on our portable trainer were able to improve objectively and
      subjectively by both external and internal evaluations. Thus, our system will
      allow trainees to develop their laparoscopic skills in an inexpensive manner in
      the comfort of their own home.

PMID- 15992879
TI  - Robotic-assisted laparoscopic dismembered pyeloplasty.
AB  - OBJECTIVES: To evaluate the feasibility and efficacy of robotic-assisted
      laparoscopic pyeloplasty. Laparoscopic pyeloplasty has been shown to have a
      success rate comparable to that of the open surgical approach. However, the steep
      learning curve has hindered its acceptance into mainstream urologic practice. The
      introduction of robotic assistance provides advantages that have the potential to
      facilitate precise dissection and intracorporeal suturing. METHODS: A total of 50
      patients underwent robotic-assisted laparoscopic dismembered pyeloplasty. A four
      trocar technique was used. Most patients were discharged home on day 1, with
      stent removal at 3 weeks. Patency of the ureteropelvic junction was assessed in
      all patients with mercaptotriglycylglycine Lasix renograms at 1, 3, 6, 9, and 12
      months, then every 6 months for 1 year, and then yearly. RESULTS: Each patient
      underwent a successful procedure without open conversion or transfusion. The
      average estimated blood loss was 40 mL. The operative time averaged 122 minutes
      (range 60 to 330) overall. Crossing vessels were present in 30% of the patients
      and were preserved in all cases. The time for the anastomosis averaged 20 minutes
      (range 10 to 100). Intraoperatively, no complications occurred. Postoperatively,
      the average hospital stay was 1.1 days. The stents were removed at an average of
      20 days (range 14 to 28) postoperatively. The average follow-up was 11.7 months;
      at the last follow-up visit, each patient was doing well. Of the 50 patients, 48
      underwent one or more renograms, demonstrating stable renal function, improved
      drainage, and no evidence of recurrent obstruction. CONCLUSIONS: Robotic-assisted
      laparoscopic pyeloplasty is a feasible technique for ureteropelvic junction
      reconstruction. The procedure provides a minimally invasive alternative with good
      short-term results.

PMID- 15992881
TI  - Outpatient laparoscopic pyeloplasty.
AB  - OBJECTIVES: To assess the feasibility of ambulatory laparoscopic pyeloplasty.
      Laparoscopic pyeloplasty aims to reproduce the excellent functional outcomes of
      open pyeloplasty while diminishing procedural morbidity. METHODS: Six patients
      fulfilled specific inclusion criteria for outpatient laparoscopic pyeloplasty:
      informed consent, body mass index of 40 kg/m2 or less, primary ureteropelvic
      junction obstruction, uncomplicated laparoscopic surgery completed by 12:00 pm,
      and postoperative pain control by oral analgesics. All patients had a double-J
      ureteral stent placed cystoscopically before laparoscopic access. No drains were
      placed postoperatively. RESULTS: All 6 patients successfully underwent
      laparoscopic dismembered pyeloplasty (3 left, 3 right) using the retroperitoneal
      (n = 5) or transperitoneal (n = 1) approach. The average patient age was 22
      years. The mean surgical time was 223 minutes (range 165 to 270), the mean blood
      loss was 82 mL (range 10 to 250), and the mean postoperative hospital stay was
      359 minutes (range 226 to 424). Postoperative analgesia comprised a mean of 6 mg
      morphine sulfate and 32 mg of ketorolac. No complications or readmissions
      occurred postoperatively. Intravenous urography and Lasix technetium-99m
      mercaptoacetyltriglycine renal scans documented resolution of obstruction. With
      long-term follow-up (mean 38.4 months), no recurrences have developed.
      CONCLUSIONS: We report our initial series of ambulatory laparoscopic pyeloplasty.
      In this well-selected patient population, outpatient pyeloplasty was feasible and
      safe.

PMID- 15992882
TI  - Vascular complications after percutaneous nephrolithotomy: are there any
      predictive factors?
AB  - OBJECTIVES: To evaluate the severe hemorrhagic complications of percutaneous
      nephrolithotomy (PNL) and their management and to analyze the predictive factors.
      METHODS: We retrospectively analyzed the data of 1854 patients who had undergone
      PNL for removal of renal calculi at our institute between 1993 and 2003. All
      patients were resuscitated with intravenous fluids and blood transfusions.
      Patients in whom bleeding did not respond to conservative means underwent
      angiography and subsequent embolization. Multivariate analyses were done to
      determine the various factors responsible for the occurrence of these lesions.
      RESULTS: Of the 1854 patients, 27 (1.4%), with a mean age of 38.6 years (range 19
      to 63) required angiography and/or embolization for bleeding control. The mean
      time to the onset of hemorrhage was 8 days (range 2 to 18). Renal arteriography
      revealed pseudoaneurysm in 13, arteriovenous fistula in 6, a combination of both
      in 4, lumbar artery injury in 1, and no lesion in 3 patients. In 22 patients,
      successful embolization of the offending vessel was achieved and in 2 the
      hematuria recurred. These 2 patients underwent repeat angiography and
      embolization of the lesion. Metallic coils were used in 13, Gelfoam in 5, and
      coils and Gelfoam in 8 patients. On multivariate analysis, only stone size was
      the significant factor predicting for the occurrence of these vascular
      complications. CONCLUSIONS: Severe hematuria is a rare complication of PNL that
      can be successfully managed with angioembolization. Our results indicated that
      stone size significantly predicted for the occurrence of lesions in patients
      undergoing PNL for symptomatic stone disease.

PMID- 15992883
TI  - Laparoscopic renal parenchymal hypothermia with novel ice-slush deployment
      mechanism.
AB  - OBJECTIVES: To report the development of a novel, simple-to-use method for
      laparoscopic deployment of fine-quality saline ice slush by way of a 10-mm end
      effector for laparoscopic parenchymal hypothermia. METHODS: A mechanism for
      making fine ice slush was created, and a 10-mm laparoscopic end-effector was
      designed and constructed for deployment of the ice slush. The novel ice slush
      deployment system was tested in a porcine model and compared with that of
      standard open ice slush cooling. After atraumatic hilar clamping, the cortical
      and medullary temperatures in the upper, middle, and lower poles were measured
      with thermocouples. RESULTS: Six pigs were evaluated in each group. In all cases,
      the kidneys were successfully cooled to our goal temperature of 15 degrees to 25
      degrees C within 10 minutes and were maintained at the target temperature for 1
      hour. The core body temperature for the slush group was decreased by 3 degrees C
      but did not change in the open group. The renal temperatures quickly returned to
      normal on unclamping of the renal hilum. One pig in the open group died of
      acidosis and another in the same group experienced thrombosis of the renal
      artery. No complications occurred in the laparoscopic group. CONCLUSIONS: We
      describe a novel, simple-to-use mechanism for producing and delivering fine ice
      slush in a laparoscopic setting. The technique achieves optimal parenchymal
      hypothermia expeditiously.

PMID- 15992884
TI  - Failed percutaneous balloon dilation for renal access: incidence and risk
      factors.
AB  - OBJECTIVES: To present our experience using balloon dilation and discuss
      secondary techniques to establish a percutaneous tract when balloon dilation
      fails. Balloon dilation is a safe and effective method to achieve percutaneous
      renal access, but it is not uniformly successful. Also, the failure rate and risk
      factors have not been well documented. METHODS: We retrospectively reviewed our
      last 99 consecutive percutaneous renal procedures using a balloon system as our
      initial dilation modality. In all cases, the urologist achieved needle access. We
      determined the balloon failure rate, relationship to prior renal surgery and
      other patient-related factors, and success rate using secondary techniques of
      tract dilation. RESULTS: The balloon did not adequately dilate a tract in 17 (17%
      failure rate) of 99 cases. The risk factors for failure included a history of
      prior ipsilateral renal surgery (25% failure rate versus 8% without surgery) and
      subcostal compared with supracostal puncture (18% versus 9% failure rate). The
      failure rate was not increased when stratified by laterality, stone composition,
      stone size and location, or history of ipsilateral renal infection. Amplatz
      dilators were used in 16 refractory cases and were successful in 15. Metal Alken
      dilators were successfully used in 2 patients. CONCLUSIONS: The balloon dilation
      system is commonly used as the primary modality to establish percutaneous renal
      access. Although safe and effective (83%), the success rate drops dramatically in
      patients with prior ipsilateral renal surgery. Knowledge and skill with
      alternative dilation systems, such as Amplatz or metal Alken dilators, are
      necessary to successfully gain entry into all renal collecting systems.

PMID- 15992885
TI  - Tamsulosin treatment increases clinical success rate of single extracorporeal
      shock wave lithotripsy of renal stones.
AB  - OBJECTIVES: To design a randomized, no-treatment, controlled, prospective study
      to determine whether the administration of tamsulosin, as adjunctive medical
      therapy, increases the efficacy of one extracorporeal shock wave lithotripsy
      (ESWL) session to treat renal stones and decreases the use of analgesic drugs
      after the procedure. METHODS: A total of 130 patients underwent a single ESWL
      session to treat solitary radiopaque renal stones 4 to 20 mm in diameter. After
      treatment, all patients were randomly assigned to receive our standard medical
      therapy alone (controls) or in association with 0.4 mg tamsulosin daily for a
      maximum of 12 weeks. All 130 patients were followed up for 3 months or until an
      alternative treatment was given. RESULTS: Of the 130 patients, 78.5% of those
      receiving tamsulosin and 60% of controls had achieved clinical success at 3
      months (P = 0.037). When we stratified patients according to stone size, for
      those with a stone size larger than 10 mm, the success rate was significantly
      greater in the tamsulosin group (P = 0.028). Renoureteral colic occurred in 76.9%
      of patients treated with standard therapy but in only 26.1% of those receiving
      tamsulosin (P < 0.001). The mean cumulative diclofenac dose was 375 mg per
      patient in the tamsulosin group and 675 mg per patient in the control group (P <
      0.001). CONCLUSIONS: The results of our study have demonstrated that tamsulosin
      therapy, as an adjunctive medical therapy after ESWL, is more effective than
      lithotripsy alone for the treatment of patients with large renal stones and is
      equally safe. In addition, our results also indicated that adjunctive treatment
      with tamsulosin could decrease the use of analgesic drugs after ESWL.

PMID- 15992886
TI  - Sustained intravesical interferon protein exposure is achieved using an
      adenoviral-mediated gene delivery system: a study in rats evaluating dosing
      regimens.
AB  - OBJECTIVES: To evaluate whether a recombinant replication-deficient adenovirus
      containing the secreted human interferon alpha-2b gene (rAd-IFN) could improve
      the tissue and urine levels of IFN protein by transducing the urothelium with the
      secreted human IFN-alpha gene. We also assessed whether varying the interval
      between rAd-IFN/Syn3 treatments would improve the duration and levels of gene
      expression. METHODS: The rats received intravesical administration of rAd-IFN at
      varying concentrations in a formulation containing Syn3, an agent identified that
      facilitates passage of the adenovirus through the protective barrier of the
      bladder. Urine was collected daily for 7 days, and human IFN was measured in the
      urine by enzyme-linked immunosorbent assay. For the redosing studies, the animals
      received a second dose at varying intervals ranging from 1 to 7 days after the
      first dose or at longer intervals (30, 60, or 90 days). RESULTS: Rats that
      received intravesical administration of rAd-IFN in a Syn3 formulation expressed
      levels of human IFN protein in their urine at peak concentrations of 50,000 to
      100,000 pg/mL, but were undetectable by 7 days. Expression was localized to the
      bladder with only minimal systemic exposure to IFN. Short-term redosing
      marginally improved the IFN urine concentrations, with maximal levels achieved
      when a second dose was administered 3 days after a first dose. Although gene
      expression was attenuated when a second dose was given 5 to 7 days after the
      first treatment, the levels and duration of IFN expression recovered when the
      interval was increased to 90 days. CONCLUSIONS: Intravesical treatment with rAd
      IFN facilitates high levels of IFN transgene exposure and may be a new approach
      to treating superficial bladder cancer.

PMID- 15992887
TI  - Effect of androgen concentration on seminal vesicle blood flow in rats
      establishment of new highly sensitive simultaneous androgen measurement method.
AB  - OBJECTIVES: To clarify the effect of androgen concentration on blood flow
      regulation in seminal vesicles and to identify the androgen most responsible for
      this effect. METHODS: The androgen concentrations in the seminal vesicles and the
      seminal vesicle blood flow were measured at 0, 3, 6, 12, 24, 48, and 72 hours
      after castration. The androgen concentration was measured with a newly developed
      highly sensitive simultaneous androgen quantification method that uses liquid
      chromatography-tandem mass spectrometry. The blood flow was measured with the
      radioactive microsphere injection method. The change in seminal vesicle blood
      flow in 6-hour castrated rats after administration of 3 mg/kg testosterone, 3
      mg/kg dihydrotestosterone (DHT), 3 mg/kg dehydroepiandrosterone, or 3 mg/kg
      testosterone plus 20 mg/kg finasteride was evaluated. RESULTS: A correlation was
      observed between the DHT concentration and blood flow in the rat seminal vesicle
      after castration. The DHT concentration and blood flow decreased after castration
      to 31.6% and 37.9%, respectively, of the normal level at 6 hours. The decline in
      DHT concentration and blood flow decreased further thereafter to 2.2% and 18.1%,
      respectively, of the normal level at 72 hours. Both testosterone and DHT fully
      restored the organ blood flow in castrated rat seminal vesicles. However, the
      blood-flow-increasing effect of testosterone was attenuated by more than 50% when
      administered in combination with finasteride. Dehydroepiandrosterone did not
      increase seminal vesicle blood flow. CONCLUSIONS: The results of our study showed
      a strong correlation between the organ DHT concentration and blood flow in rat
      seminal vesicles. Of the various androgens, the most active androgen in the
      regulation of seminal vesicle blood flow was DHT.

PMID- 15992888
TI  - Effect of ethanol on protection of urinary bladder function by grape suspensions.
AB  - OBJECTIVES: To compare the protective effects of grape suspensions prepared in an
      aqueous vehicle with grape suspensions prepared in an 8% ethanol vehicle in
      rabbits subjected to partial outlet obstruction. The hypothesis was that the
      presence of ethanol would increase the absorption of the beneficial components of
      the grape suspensions and thus increase their protective ability. The use of
      ethanol in these studies was not to simulate wine. METHODS: A total of 48 New
      Zealand white rabbits were separated into eight groups of 6 rabbits each. Groups
      1 and 3 were pretreated by oral gavage for 3 weeks with grape suspensions in
      water; groups 2 and 4 were treated with vehicle. Groups 5 and 7 were treated with
      the grape suspensions in 8% ethanol, and groups 6 and 8 were treated with ethanol
      vehicle. Groups 1, 2, 5, and 6 underwent sham operations, and groups 3, 4, 7, and
      8 underwent partial outlet obstruction. Three weeks after surgery, the rabbits
      were evaluated. RESULTS: The bladder weight had significantly increased in all
      obstructed groups. The contractile responses to field stimulation and carbachol
      were reduced in all obstructed groups, although the responses in both grape
      treated groups were greater than both vehicle-treated groups. The contractile
      responses to potassium chloride were significantly reduced by partial outlet
      obstruction in both obstructed groups similarly. CONCLUSIONS: Both grape
      suspensions provided protection against obstructive-induced bladder dysfunction.
      The ethanol preparation of the grape suspension was not better than the aqueous
      preparation.

PMID- 15992889
TI  - In vivo effects of botulinum toxin A on visceral sensory function in chronic
      spinal cord-injured rats.
AB  - OBJECTIVES: To analyze the in vivo effects of botulinum toxin type A (BTX-A) on
      visceral sensory function in chronic spinal cord-injured (SCI) rats. METHODS: One
      group of rats underwent spinal cord transection at the T8-T9 level (SCI) and the
      other group was left untreated. In 21 days, baseline open cystometrography (CMG)
      was performed. The rats were then treated intravesically with either 1 mL of 1%
      protamine sulfate (PS) to increase urothelial permeability or saline, followed by
      either 1 mL of BTX-A (20 U) or saline. CMG was repeated 48 hours after
      instillation, and any changes in the bladder contraction frequency and amplitude
      were evaluated. RESULTS: After the instillation of PS and BTX-A or BTX-A alone,
      the bladder contraction frequency was significantly decreased in the SCI rats
      compared with the control rats (P < 0.05); no change was seen in the contraction
      amplitude. When normal rats were given intravesical PS and/or BTX-A, or SCI
      animals were treated with PS alone, neither the frequency nor the amplitude of
      the contractions was affected. Also, no significant differences were found in the
      bladder contraction frequency or amplitude of contractions in any animal treated
      with instillation of saline alone. CONCLUSIONS: Intravesical BTX-A inhibits
      bladder sensory mechanisms by reducing the frequency of bladder contractions in
      an SCI rat model. Furthermore, our results suggest that intravesically applied
      BTX-A does not penetrate to the smooth muscle layer even after PS disruption of
      the bladder urothelium. These findings may have important clinical applications
      in treating overactive bladders after SCI.

PMID- 15992890
TI  - Effect of vascular endothelial growth factor on regeneration of bladder acellular
      matrix graft: histologic and functional evaluation.
AB  - OBJECTIVES: To evaluate the effect of vascular endothelial growth factor (VEGF)
      on regeneration of the bladder acellular matrix graft (BAMG). METHODS: A total of
      40 female rats were divided into two groups. In the experimental group (VEGF+),
      the BAMG was incubated in VEGF and VEGF was injected into the host bladder. In
      the control rats, sterile solution replaced VEGF. Urodynamic studies were
      performed at grafting and repeated at 2, 4, 8, and 12 weeks. The bladders were
      harvested for histologic examination. Immunostaining was used to monitor VEGF
      treatment by examining VEGF and VEGF-receptor 2 expression. Neovascularity,
      smooth muscle induction, and nerve regeneration were assessed
      immunohistochemically. RESULTS: Increased VEGF and VEGF-receptor 2 were present
      in the VEGF+ rats 2 weeks after grafting. The maximal intravesical pressure was
      significantly greater in the VEGF+ group at 2 weeks than in the controls, despite
      the same bladder capacity. At 4 weeks, a significant increase in bladder capacity
      and a decrease in the postvoid residual volume ratio were observed. After 8
      weeks, no differences were noted in the urodynamic parameters between the two
      groups. Numerous alpha-actin-positive spindle cells were observed in the VEGF+
      rats at 2 weeks, and the smooth muscle content was significantly greater at all
      points. Enhanced angiogenesis was noted at 2 and 4 weeks. Nerve fibers were
      observed at 4 weeks and nerve growth factor-positive cells were significantly
      greater at 2, 4, and 8 weeks in the VEGF+ rats. CONCLUSIONS: Administration of
      VEGF had significant effects on the BAMG at early periods after grafting. Our
      results have shown that VEGF enhances BAMG regeneration in rats as assessed by
      functional restoration and histologic examination.

PMID- 15992891
TI  - Chronic bacterial prostatitis: an evolving clinical enigma.

PMID- 15992892
TI  - erbB receptor expression patterns in human bladder cancer.
AB  - OBJECTIVES: To investigate expression patterns of erbB receptors in a panel of 58
      human bladder tumors. Aberrant functional and structural interactions of erbB
      type I receptor tyrosine kinase cell surface receptors are important in the
      development and maintenance of the malignant phenotype. Few studies have focused
      on the remaining family members or patterns of receptor coexpression in
      urothelial cancer. METHODS: Frozen tumor samples from 58 patients with newly
      diagnosed bladder cancer were collected; 18 had Stage Ta, 20 Stage T1, and 20 had
      Stage T2 or worse. The grade was G1 in 5, G2 in 24, and G3 in 29 patients. Seven
      normal urothelial samples were obtained from patients with benign urologic
      conditions. The tumor material was probed using conventional immunoblotting and
      enhanced chemiluminescence. The blots were captured with digital imaging, and
      protein expression was quantified with gel analysis software. RESULTS: Most
      tumors exhibited detectable expression of at least one erbB receptor. Examples of
      coexpression of epidermal growth factor receptor (EGFr) and erbB-2 were also
      found. Detectable erbB-3 or erbB-4 protein expression was lacking in this series.
      Compared with other tumors, the T1 samples exhibited the greatest mean levels of
      erbB-2 protein expression (P = 0.0028). Of the 58 tumors, 10 (17.2%) coexpressed
      EGFr and erbB-2; this was associated with T1 disease (P = 0.03). CONCLUSIONS:
      Varied levels of expression of both EGFr and erbB-2 appear to exist in human
      bladder cancer. These preliminary data do not support erbB-3/4 as major
      protagonists in this tumor system. The observations presented suggest a role for
      EGFr and erbB-2 in the development and progression of bladder cancer that should
      be explored further.

PMID- 15992893
TI  - Delayed onset bleomycin-induced pneumonitis.
AB  - We describe a 39-year-old male patient who developed bleomycin-induced
      pneumonitis 2 years after completion of chemotherapy for nonseminomatous
      testicular cancer. Bleomycin sometimes causes fatal pulmonary toxicity, including
      bleomycin-induced pneumonitis. The central event in the development of
      pneumonitis is endothelial damage of the lung vasculature due to bleomycin
      induced cytokines and free radicals. Pulmonary toxicity usually begins at
      bleomycin administration. The development of bleomycin-induced pneumonitis up to
      6 months after bleomycin therapy has also been reported. We report a patient who
      developed bleomycin-induced pneumonitis 2 years after the initiation of bleomycin
      containing chemotherapy regimens.

PMID- 15992894
TI  - Plasmacytoid transitional cell carcinoma of the urinary bladder.
AB  - A case of rare plasmacytoid transitional cell carcinoma of the urinary bladder in
      a 60-year old man is described. The presence of end-stage disease did not allow
      for any efficacious therapy. Immunohistochemistry showed the tumor cells to be
      reactive for epithelial markers and syndecan-1 (CD138).

PMID- 15992895
TI  - True hermaphroditism presenting in adulthood as a scrotal mass.

PMID- 15992896
TI  - Salvage of end-stage erectile dysfunction using vascularized fibula as autologous
      implant.
AB  - INTRODUCTION: Patients in whom medical and surgical options for the treatment of
      erectile dysfunction have failed pose a unique challenge to reconstructive
      genitourinary surgeons. We report a novel reconstructive option for the treatment
      of end-stage erectile dysfunction using a microsurgically transferred
      vascularized fibula as an autologous implant in a patient in whom multiple
      inflatable prostheses had failed. TECHNICAL CONSIDERATIONS: A reconstructive
      team, consisting of urologic and plastic reconstructive surgeons, transferred a
      vascularized fibula into the corporeal body in 1 patient to restore sexual
      function. Using this technique, successful intercourse was achieved by 6 months
      of follow-up. We describe the surgical technique of autologous implant of a
      vascularized fibula in the salvage treatment of end-stage erectile dysfunction.
      CONCLUSIONS: Patients with multiple failed inflatable penile implants can present
      a formidable challenge to reconstructive surgeons with regard to restoring
      adequate sexual function. The standard approach to the patient after repeated
      episodes of unsuccessful salvage of penile prosthesis due to infection and/or
      extrusion is to remove the prosthesis, leaving the patient impotent. Vascularized
      autologous tissue transfer provides an option to salvage end-stage erectile
      dysfunction.

PMID- 15992897
TI  - Laparoscopic fenestration of lymphoceles after kidney transplantation with
      diaphanoscopic guidance.
AB  - In laparoscopic fenestration of lymphoceles after kidney transplantation,
      identification of the correct site of incision is sometimes difficult. We
      developed a new technique, using diaphanoscopy in 3 patients. After ultrasound
      guided puncture and dilation, the correct incision site is identified by white
      light with a cystoscope inserted into the lymphocele cavity.

PMID- 15992898
TI  - Tissue expansion in management of failed phallic reconstruction: initial report
      of clinical series.
AB  - OBJECTIVES: To report the first significant experience with the use of tissue
      expanders in phallic reconstruction. Patients who have undergone multiple failed
      surgical procedures for repair of hypospadias or epispadias often have minimal
      residual skin available for additional reconstructive efforts. Although a variety
      of graft options exist, local skin expansion can provide pigment and texture
      matched skin for reconstructive procedures. METHODS: We reviewed our experience
      with tissue expansion in patients after multiple failed phallic reconstructive
      efforts. A total of 18 males (mean age 13.2 years) with an underlying diagnosis
      of exstrophy/epispadias (n = 9), hypospadias (n = 7), partial androgen
      insensitivity syndrome (n = 1), and congenital adrenal hyperplasia (n = 1) had
      penile tissue expanders placed and inflated during a 6-week period. The expanders
      were removed at penile reconstruction. RESULTS: Tissue expanders were placed in
      18 patients and successfully inflated in 17 patients. Good surgical results
      requiring no additional procedures were obtained in 8 (47%) of the 17 patients.
      Two patients subsequently underwent repeated tissue expansion; one of these
      patients had a good outcome after two expansions and supplemental pedicle graft,
      and the other had persistent fistulas and required a forearm graft. The implants
      were replaced because of extrusion in 3 patients and removed for malfunction,
      erosion, or infection in 1 patient each. CONCLUSIONS: The use of tissue expansion
      provides a useful option for reconstruction in patients with minimal or scarred
      skin after multiple failed prior phallic reconstructions and offers certain
      benefits over the transfer of free grafts. The availability of smaller tissue
      expanders makes this technique feasible even for young children.

PMID- 15992899
TI  - Long-term urologic, orthopedic, and psychological outcome of posterior urethral
      rupture in children.
AB  - OBJECTIVES: To evaluate the long-term urologic, orthopedic, and psychological
      outcome of children after posterior urethral rupture (PUR) due to pelvic trauma.
      METHODS: We retrospectively reviewed the records of 49 children with PUR from
      1986 to 2000. The long-term urologic results were determined by voiding function,
      continence, and erectile function. The orthopedic results were determined by
      pelvic radiography and a questionnaire. Psychiatric diagnoses were made using the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV),
      criteria and the Structured Clinical Interview for DSM-IV Axis I Disorders.
      RESULTS: The mean follow-up was 12 years (range 4 to 17). The average age was 8
      years at the time of the trauma and 20 years at the last follow-up. Urethral
      continuity was achieved in 97.9% of the children. Of the 49 patients, 19 had at
      least one urologic complication, 18 had orthopedic pathologic findings, and 21
      had psychiatric diagnoses. The number of urologic procedures required (more than
      three), presence of long-term complications, and total number of hospitalizations
      (more than three) secondary to the injury significantly affected the development
      of a psychological disorder. CONCLUSIONS: The results of our study have shown
      that posttraumatic PUR in children is associated with a significant rate of long
      term complications. Nonoperative treatment of pediatric pelvic fractures
      associated with PUR has been quite successful. Repeated operations, the presence
      of long-term urologic complications, and frequent and long hospital stays result
      in serious attendant psychological problems. Therefore, careful and prolonged
      follow-up of posttraumatic urethral injury with a multidisciplinary approach is
      necessary to provide better outcomes and a better quality of physical and social
      life for these children.

PMID- 15992900
TI  - Deep venous thrombosis in pediatric patients with myelomeningocele undergoing
      urologic reconstruction--do we need to reconsider prophylaxis?
AB  - OBJECTIVES: To review a single surgeon's experience with the development of
      postoperative deep venous thrombosis after urologic reconstruction in the
      myelomeningocele population. This complication is rarely reported in this
      population, despite the multiple risk factors. We reviewed the risk factors for
      the development of deep venous thrombosis and present options for treatment and
      prevention of this potentially life-threatening complication. METHODS: We
      reviewed a single surgeon's population of myelomeningocele patients who had
      undergone urologic reconstruction during a 7-year period. This series was
      examined retrospectively for the development of deep venous thrombosis and its
      evaluation and treatment. RESULTS: A total of 61 patients with myelomeningocele
      who had undergone urologic reconstruction during a 7-year period were identified.
      Of these 61 patients, deep venous thrombosis was diagnosed in 2. The risk factors
      common in this population were chronic immobility, recent surgery, and infection.
      CONCLUSIONS: Deep venous thrombosis is a rarely reported complication after
      urologic reconstruction in the myelomeningocele population. The preoperative risk
      factors should be evaluated. Diligent surveillance postoperatively should be
      maintained. Evaluation and treatment should be prompt to decrease the risk of
      serious pulmonary complications.

PMID- 15992901
TI  - Supplement use among men with prostate cancer.
AB  - OBJECTIVES: To characterize supplement use within a sample population of men
      diagnosed with prostate cancer. METHODS: A census of men diagnosed with prostate
      cancer at Duke University Medical Center from 1997 to 2002 (n = 1402) was mailed
      a survey that ascertained data on health status, education, diet, exercise,
      smoking status, and information on supplement use. Differences between
      demographic and treatment subgroups were described and tested, as was change in
      supplement use after diagnosis. RESULTS: Data from 805 respondents indicated that
      a majority (73%) used supplements, and 68% claimed that this information was
      shared with their cancer care provider. The most commonly reported supplements
      were multivitamins (56%), vitamin E (43%), vitamin C (33%), and calcium (26%). On
      average, 2.7 +/- 2.8 supplements per day were taken, and use increased
      significantly after diagnosis for most supplements. Use was significantly higher
      among men who were white (P = 0.043), were more highly educated (P = 0.002),
      exercise regularly (P = 0.020), and who consume five or more daily servings of
      fruits and vegetables (P = 0.040). CONCLUSIONS: A high percentage of men with
      prostate cancer take supplements, especially those who are white, more educated,
      and who pursue healthful behaviors. Systematic means of capturing these data are
      necessary to begin to understand the potential impact of supplements on disease
      outcome, especially because no data exist to suggest that supplements are of any
      benefit after diagnosis.

PMID- 15992902
TI  - Modified running vesicourethral anastomosis after robotically assisted
      laparoscopic radical prostatectomy: use of solitary Lapra-Ty to secure posterior
      approximation.
AB  - OBJECTIVES: We describe a novel method of ensuring posterior approximation and
      preventing urinary leak during the running anastomosis of robotically assisted
      laparoscopic prostatectomy. METHODS: Two 3-0 Monocryl RB-1 sutures are tied end
      to-end. The undyed suture is placed first at the 5-o'clock position on the
      bladder side outside-in and then through the urethra at the same location inside
      out. Proceeding clockwise, the suture is placed twice more through both the
      bladder and the urethra. With gentle manipulation, the suture is cinched down to
      provide secure posterior approximation; however, if tension is released from the
      suture coming from the urethra, the approximation may loosen and could result in
      a potential "gap" and site for anastomotic leakage. To prevent potential
      loosening, tension is maintained on the stitch as a single Lapra-Ty is placed at
      the base of the suture as it leaves the urethra. When the tension is released,
      the posterior approximation is tightly maintained and the remaining anastomosis
      is completed. RESULTS: We have performed 110 robotically assisted laparoscopic
      prostatectomies. Six urinary leaks requiring prolonged catheterization were
      identified in our first 90 patients (6.7%). We have not experienced any urinary
      leakage or short-term complications in the subsequent 20 patients using this
      technique. CONCLUSIONS: We describe a novel technique to ensure secure posterior
      approximation during the vesicourethral anastomosis after robotically assisted
      laparoscopic prostatectomy. A single Lapra-Ty clip placed early during the
      anastomosis prevents potential "gaps" in the approximation that may be the source
      of troublesome leakage.

PMID- 15992903
TI  - Preoperative PSA and progression-free survival after radical prostatectomy for
      Stage T1c disease.
AB  - OBJECTIVES: To examine biochemical progression-free survival (PFS) rates as a
      function of preoperative prostate-specific antigen (PSA) in patients with
      clinical Stage T1c prostate cancer treated with radical prostatectomy.
      Controversy exists about whether performing prostate biopsies for PSA levels in
      the 2.6 to 4.0 ng/mL range provides a PFS advantage compared with detection at
      higher PSA ranges. METHODS: A total of 2804 men with clinical Stage T1c prostate
      cancer were treated with radical retropubic prostatectomy and monitored
      prospectively. The study parameters included preoperative PSA level, pathologic
      tumor stage, and Gleason grade. Patients were grouped into four clinically
      relevant strata according to their preoperative PSA level: 2.6 to 4.0, 4.1 to
      7.0, 7.1 to 10.0, and greater than 10 ng/mL. The primary outcome was the 10-year
      actuarial biochemical PFS estimate generated using the Kaplan-Meier method. We
      compared the strata using the log-rank test. Cancer progression rates were
      compared using the Cochran Armitage test for trend. The chi-square test was used
      to compare the pathologic parameters among the PSA strata. RESULTS: Of the men
      with a preoperative PSA level of 2.6 to 4.0, 4.1 to 7.0, 7.1 to 10.0, and greater
      than 10.0 ng/mL, 81%, 74%, 72%, and 60%, respectively, had organ-confined disease
      (P = 0.001) and 23%, 28%, 35%, and 47%, respectively, had a pathologic Gleason
      grade of 7 or greater (P = 0.001). The corresponding 10-year PFS estimates were
      88%, 80%, 76%, and 61% (P = 0.0001, for trend). CONCLUSIONS: Among men with
      clinical Stage T1c prostate cancer, those with a PSA level of 2.6 to 4.0 ng/mL
      had the greatest rate of organ-confined disease, lowest pathologic Gleason grade,
      and greatest 10-year PFS rate.

PMID- 15992904
TI  - Isolated seminal vesicle invasion imparts better outcomes after radical
      retropubic prostatectomy for clinically localized prostate cancer: prognostic
      stratification of pt3b disease by nodal and margin status.
AB  - OBJECTIVES: To examine the survival differences in men with seminal vesicle
      invasion (SVI) according to surgical margin (SM) and nodal (N) status to
      characterize the influence of isolated SVI on disease progression after radical
      retropubic prostatectomy for clinically localized prostate cancer. METHODS: We
      reviewed the records of 941 men who underwent radical retropubic prostatectomy
      for clinically localized prostate cancer between 1984 and 2002. Three groups with
      evidence of SVI (SM-/N-, SM+/N-, and N+) were analyzed to identify differences in
      age, preoperative prostate-specific antigen (PSA) level, biopsy Gleason score,
      surgical Gleason score, time to PSA progression, follow-up time, and cancer
      specific and overall survival. Kaplan-Meier estimates and univariate and
      multivariate calculations were generated to examine differences in biochemical
      free survival. RESULTS: Of 941 patients, 87 were identified with SVI; of these,
      28 (32.2%) were SM-/N-, 35 (40.2%) were SM+/N-, and 24 (27.6%) were N+. The
      median follow-up for all patients was 70 months. The 5-year biochemical
      progression-free rate for SM-/N-, SM+/N-, and N+ patients was 71.9%, 36.6%, and
      25.9%, respectively. The median time to PSA progression for SM-/N-, SM+/N-, and
      N+ patients was 26, 16, and 6 months, respectively. The clinical stage,
      pretreatment PSA level, and margin and node status were statistically predictive
      (P < 0.05) on univariate analyses; however, only positive margin status
      approached statistical significance on multivariate analysis (P = 0.06). The
      overall and cancer-specific 5-year survival rates for SM-/N-, SM+/N-, and N+
      patients were 89% and 100%, 79% and 97%, and 78% and 86%, respectively.
      CONCLUSIONS: Isolated SVI is associated with lower rates of, and longer intervals
      to, biochemical failure compared with SVI with positive margins and/or regional
      lymph node involvement.

PMID- 15992905
TI  - Adverse effect of radical prostatectomy on nocturia and voiding frequency
      symptoms.
AB  - OBJECTIVES: To evaluate the impact of retropubic radical prostatectomy (RP) on
      urinary incontinence and obstructive/irritative urinary symptoms, according to
      global self-assessment instruments. METHODS: Self-report assessments were
      provided by 120 patients who underwent RP alone. The University of California,
      Los Angeles Prostate Cancer Index (UCLA PCI), the International Prostate Symptom
      Score (IPSS), and the IPSS quality of life (QOL) score were administered before
      and 12 months after RP. RESULTS: Overall mean total IPSS and IPSS QOL scores
      showed statistically significant improvement (both P < 0.001). There were no
      differences between baseline and postoperative scores in "Voiding frequency" or
      "Nocturia" related to irritative symptoms. Moreover, RP had adverse effects on
      the nocturia and voiding frequency composites score when the analysis was limited
      to those men who reported scores of 0 or 1 for each symptom preoperatively (P <
      0.001 and P = 0.001, respectively). The urinary function score according to the
      UCLA PCI had substantially declined at 12 months compared with baseline (P <
      0.001); however, no significant differences were observed in urinary bother
      between the baseline and postoperative scores. CONCLUSIONS: Although a
      significant proportion of men complained of urinary incontinence, RP
      significantly improved IPSS and IPSS QOL scores in men with moderate or severe
      urinary symptoms. However, RP seems to have a deleterious effect on nocturia and
      voiding frequency for some men with only mild symptoms.

PMID- 15992906
TI  - Outcomes for men younger than 50 years undergoing radical prostatectomy.
AB  - OBJECTIVES: To compare the surgical outcomes after radical prostatectomy between
      men younger than 50 years and men 50 years old or older. METHODS: Between October
      1, 2000 and December 31, 2003, 790 men underwent open radical retropubic
      prostatectomy by a single surgeon. The intraoperative, perioperative, and
      postoperative parameters were recorded in real time and entered into a database.
      The outcomes were compared for 66 men younger than 50 years of age (group 1)
      versus 724 men who were 50 years old or older (group 2). RESULTS: The pathologic
      stage, percentage of cancer in the surgical specimen, positive surgical margin
      rate, and Gleason score were not significantly different among the two age
      groups. No significant difference was found in the risk factors for prostate
      cancer between groups 1 and 2 (33.3% versus 28.9%, respectively; P = 0.63). The
      operative complications were exceedingly low in both groups. Of the men in groups
      1 and 2, 93.3% and 97.1% achieved continence, respectively (P = 0.26). Of the
      potent men at baseline who underwent bilateral nerve-sparing prostatectomy, 100%
      of men in group 1 versus 81.4% in group 2 (P = 0.02) were having erections
      adequate for intercourse with or without phosphodiesterase-5 inhibitors or
      intracavernous injection therapy, as determined by direct patient interview. Of
      the men who underwent bilateral nerve-sparing radical retropubic prostatectomy,
      78.3% of group 1 versus 62.6% of group 2 (P = 0.14) were potent with or without
      phosphodiesterase-5 inhibitors. CONCLUSIONS: The preoperative and pathologic
      predictors of organ-confined disease and biochemical recurrence were similar in
      both age groups. The results of this study have demonstrated that radical
      retropubic prostatectomy can be performed with good results and low complication
      rates in men with localized prostate cancer who are younger than 50 years of age.

PMID- 15992907
TI  - Immunohistochemical study of chromogranin A in Stage D2 prostate cancer.
AB  - OBJECTIVES: To study the clinical and pathologic factors that affect the time to
      recurrence after hormonal therapy in patients with Stage D2 prostate cancer and
      to determine whether cells positive for chromogranin A (CgA) in tissue biopsied
      at diagnosis is a useful marker for predicting the duration to recurrence after
      hormonal therapy. METHODS: A total of 50 patients diagnosed with Stage D2
      prostate cancer at our institution from January 1998 to December 2001 were
      studied. The needle prostate biopsy specimens obtained at diagnosis were stained
      by immunohistochemistry using the labeled streptavidin biotin method, and the
      results were considered positive if CgA-positive cells constituted 10% or more of
      the tumor area. RESULTS: No significant differences were found between patients
      on the basis of the time to recurrence of less than 2 years versus 2 years or
      more with respect to prostate-specific antigen level, patient age, Gleason score,
      or extent-of-disease grade. Of the 50 patients, 11 (22.0%) had positive cell
      staining for CgA. No significant differences were found between the CgA-positive
      group and the CgA-negative group in age, prostate-specific antigen level, Gleason
      score, extent-of-disease grade, T stage, or N stage. The rate of freedom from
      recurrence after 2 years as analyzed by the Kaplan-Meier method was 18.2% for the
      CgA-positive group and 47.4% for the CgA-negative group, and the CgA-positive
      group had a significantly shorter time to recurrence (P < 0.0122). CONCLUSIONS:
      The results of our study have shown that patients with overexpression of CgA
      positive cells in the prostate have a significantly shorter time to recurrence
      after hormonal therapy than patients with CgA-negative cells; thus, CgA
      expression may be a useful marker predictive of the time to recurrence.

PMID- 15992908
TI  - Analysis of impact of age and race on biochemical control after radiotherapy in
      different prostate cancer settings.
AB  - OBJECTIVES: To provide a single-institution analysis of the impact of age and
      race on biochemical control after radiotherapy (RT) administered in different
      prostate cancer scenarios. Age and race are among the most controversial
      prognostic factors in determining outcome after RT. Proper understanding of these
      prognostic factors can assist in both treatment decision-making and the general
      understanding of the natural history of prostate cancer. METHODS: The records of
      527 consecutive nonmetastatic patients undergoing RT at a single institution and
      for whom demographic, disease, treatment, and follow-up information were
      available were reviewed. The cohort was divided into two categories: locally
      advanced/localized (458 patients) and postprostatectomy (69 patients).
      Biochemical failure-free survival (BFFS) curves were compared within each group
      to determine the influence of age and race on biochemical control. RESULTS: BFFS
      curves for the entire study population did not reveal any statistically
      significant difference when separated by age (younger than 60 years versus 60 to
      69 years versus 70 years or older; 4-year BFFS 75% versus 70% versus 72%,
      respectively; P = 0.773) or by race (African American versus white; 4-year BFFS
      74% versus 70%, respectively; P = 0.469). Additionally, no statistically
      significant differences were observed as a function of stage or age within either
      category (intact prostate or postprostatectomy). CONCLUSIONS: Age and race did
      not, in our study, independently influence biochemical control after RT for
      nonmetastatic prostate cancer. On the basis of the results of this study, age and
      race should not be used as independent factors in treatment decision-making and
      in patient counseling concerning prostate cancer.

PMID- 15992909
TI  - Reduction of pulmonary migration of permanent interstitial sources in patients
      undergoing prostate brachytherapy.
AB  - OBJECTIVES: To investigate a method to decrease the problem of seed migration
      after permanent prostate brachytherapy. Permanent prostate brachytherapy can be
      performed by a number of techniques using several different seed configurations.
      All have been associated with some degree of pulmonary seed migration, and no
      studies have clearly investigated a means of decreasing this problem. METHODS: A
      total of 238 patients underwent implantation with either iodine-125 (I-125; 146
      patients) or palladium-103 (92 patients). The implant was performed in real time
      using an applicator, with the sources placed just underneath the prostatic
      capsule. Postimplant dosimetry was performed at 1 month. Routine chest x-ray was
      obtained a minimum of 4 months after implantation; 24 patients had a second chest
      x-ray taken. RESULTS: A total of 21,654 seeds were implanted (median 89, range 27
      to 220). Postimplant chest x-rays were obtained at a median of 912 days (range
      147 to 3023), and 4 patients (1.7%) experienced at least one seed embolus to the
      lung. Of the 21,654 seeds, 10 (0.005%) were found in the lungs. All 4 patients
      had received an I-125 implant, resulting in a pulmonary embolus rate for I-125 of
      2.7% (4 of 146) and for palladium-103 of 0% (0 of 92). No patients experienced
      subsequent seed migration if it was not seen on the initial film. The median dose
      delivered to 90% of the prostate volume for all patients undergoing I-125
      implantation was 172 Gy and for the 4 patients with seed migration it was 174 Gy.
      CONCLUSIONS: Seed embolism to the lungs is a rare event when patients undergo
      implantation using the real-time method. Although in our series migration was
      slightly greater with I-125 than with palladium-103, no negative effect was seen
      on the postimplant dosimetry results.

PMID- 15992910
TI  - Cancer core distribution in patients diagnosed by extended transperineal prostate
      biopsy.
AB  - OBJECTIVES: To perform systemic 22-core transperineal ultrasound-guided template
      prostate biopsies in patients with previous negative transrectal ultrasound
      guided prostate biopsy findings and evaluate the cancer core distribution.
      METHODS: Between April 2001 and December 2003, 128 men underwent systemic
      ultrasound-guided biopsy using the transperineal template technique. All patients
      had undergone at least one previous set of biopsies. Prostate biopsy was
      performed transperineally using an 18-gauge biopsy needle driven by a spring
      loaded device. Four biopsies were obtained anterior to posterior from each of
      four coronal planes in the mid-region, and three biopsies were obtained anterior
      to posterior from each of two coronal planes in the apical region. RESULTS: Of
      the 128 patients, 29 (22.7%) had cancer according to an extended transperineal
      biopsy. Patients with prostate cancer had significantly greater prostate-specific
      antigen (PSA) levels (11.4 versus 7.6 ng/mL, P = 0.0125), smaller transition zone
      volumes (12.7 versus 21.2 cm3, P = 0.0012), smaller prostate glands (31.5 versus
      44.0 cm3, P = 0.0015), and greater PSA density (0.36 versus 0.19 ng/mL/cm3, P <
      0.0001). The cancer core rates in the mid and apical parts of the anterior region
      (5.3% and 8.0%) were significantly greater than in the mid and apical parts of
      the posterior region (3.3% and 3.6%, P = 0.0297 and P = 0.0132, respectively).
      CONCLUSIONS: The results of our study have shown that transperineal approaches
      are appropriate for sampling from the anterior half of the prostate gland. In
      patients in whom the diagnosis of prostate cancer is suspected, we believe that
      systemic 22-core transperineal ultrasound-guided template prostate biopsy might
      be the next optional diagnostic step after an initial negative prostate biopsy.

PMID- 15992911
TI  - Body mass index as a predictor of prostate cancer: development versus detection
      on biopsy.
AB  - OBJECTIVES: To determine whether obesity is biologically associated with an
      increased risk of prostate cancer development, especially aggressive disease and
      to explore whether a bias may exist in our ability to detect these cancers in
      obese patients. METHODS: We evaluated the association of body mass index (BMI)
      with prostate cancer, biopsy Gleason sum, and amount of cancer using logistic and
      linear regression analyses adjusting for age at biopsy, race, prostate-specific
      antigen level, digital rectal examination findings, and prostate volume among 787
      consecutive men undergoing prostate biopsy between 1998 and 2002 at an equal
      access medical center. RESULTS: Men with a higher BMI were younger (P < 0.001),
      had lower prostate-specific antigen concentrations (P = 0.02), fewer abnormal
      digital rectal examination findings (P = 0.02), and larger prostate volumes (P <
      0.001). After adjusting for age, no overall association was found between BMI and
      the odds of being diagnosed with cancer (P trend = 0.89), although overweight and
      mild obesity were inversely associated with the diagnosis of cancer. After
      multivariable adjustment, a higher BMI was associated with an increased odds of
      being diagnosed with prostate cancer (P trend = 0.007). Among men diagnosed with
      cancer, and after multivariable adjustment, a higher BMI was associated with a
      similar percentage of biopsy tissue with cancer (P trend = 0.23), but with
      greater odds of a high Gleason sum (P trend = 0.004). CONCLUSIONS: After taking
      into account the clinical characteristics that influence the likelihood of
      finding an existent cancer, a higher BMI was positively associated with being
      diagnosed with prostate cancer. Also, among the men with cancer, a higher BMI
      increased the odds of high-grade disease. These findings suggest that obesity may
      be biologically associated with prostate cancer development and, in particular,
      with high-grade disease.

PMID- 15992912
TI  - Is serum prostate-specific antigen level affected by fasting and nonfasting?
AB  - OBJECTIVES: To determine whether the level of serum prostate-specific antigen
      (PSA) varies with fasting and nonfasting. METHODS: The study involved 80 male
      patients with normal digital rectal examination who were hospitalized for benign
      urologic problems. The patients with active urinary tract infection, urologic
      cancer, urethral catheterization, diabetes mellitus, or acute or chronic renal
      failure and those who had undergone urologic manipulations within the past 45
      days were excluded from the study. All the patients were asked to fast between
      12:00 am and 8:00 am. The next morning, 10-mL venous blood samples were obtained
      at 8:00 am. Then each patient was provided with breakfast, which was followed by
      additional serial venous serum sampling during the first and second hour. The
      patients ate lunch at 12:00 pm. The final venous serum sampling was conducted at
      2:00 pm. The serum PSA levels were determined for all the serum samples. RESULTS:
      The mean patient age was 62.42 +/- 8.75 years (range 46 to 82). The mean serum
      total PSA value at fasting and the first, second, and sixth hour was 2.78 +/-
      2.19, 2.7 +/- 2.0, 2.7 +/- 2.1, and 2.78 +/- 2.10 ng/mL, respectively. In the
      comparisons of the fasting values and first, second, and sixth hour values and
      the values at each hour with those at the other hours, no significant differences
      were observed (P > 0.05). CONCLUSIONS: According to our results, blood samples
      can be obtained for serum PSA measurement at any time of the day, regardless of
      whether the patient has fasted or not.

PMID- 15992914
TI  - Combined FDG-positron emission tomography and computed tomography for the
      detection of ovarian cancer recurrence in an inguinal hernia sac.
AB  - BACKGROUND: Ovarian cancer recurrence presenting in an inguinal hernia sac is
      rare. Only 1 case of malignant ovarian cancer growing into an inguinal hernia sac
      has been reported in the English literature. Combined positron emission
      tomography (PET) and computed tomography (CT) may have a potential role in the
      early detection and anatomical localization of recurrent ovarian cancer. CASE
      REPORT: This is the first case of occult metastasis from ovarian cancer
      recurrence growing in a right inguinal hernia sac identified using combined FDG
      PET/CT. CONCLUSION: Preoperative combined FDG-PET/CT imaging may have utility in
      the detection and anatomic localization of occult ovarian cancer recurrence,
      which may increase the likelihood of complete resection.

PMID- 15992915
TI  - Primary cervical lymphoma: report of two cases and review of the literature.
AB  - BACKGROUND: Primary lymphoma arising from the female genital tract has been
      rarely encountered. Primary cervical lymphoma is even rarer in gynecologic
      oncology practice and accounts for approximately only 1% of extranodal lymphomas.
      In this article, two cases of cervical lymphoma are presented with a review of
      the available literature. CASE HISTORIES: A 51-year-old woman presented with
      abnormal vaginal discharge. On pelvic examination, cervix was apparently normal;
      however, a solid and mobile pelvic mass was palpated. Pap smear was reported as
      HSIL at another institution. Radiological evaluation revealed a cervical mass
      with a 3 cm diameter. Histopathological evaluation of LEEP material was reported
      as diffuse large B cell lymphoma. We performed abdominal hysterectomy plus
      bilateral salphingo-oopherectomy and the patient was treated with adjuvant 6
      cycles of CHOP chemotherapy. A second case was a 49-year-old postmenopausal woman
      who had undergone a routine gynecologic follow-up examination without any
      complaint at another institution. Routine cytological smear revealed HSIL. Punch
      biopsy under colposcopic examination presented no remarkable pathology except for
      a benign inflammation. Due to discordance between cytology and histology, LEEP
      was performed under colposcopic examination, which revealed follicular lymphoma
      grade III. This patient was treated with 6 cycles CHOP chemotherapy without any
      surgery. CONCLUSION: Primary cervical lymphoma is a rare disorder. Although most
      reported cases in the literature have a normal Pap smear, some may represent with
      co-existent cytological abnormalities. Therefore, cervical lymphomas should be
      kept in mind in patients with cytological abnormalities.

PMID- 15992916
TI  - Weekly topotecan in heavily pretreated patients with recurrent epithelial ovarian
      carcinoma.
AB  - OBJECTIVE: To investigate weekly topotecan in heavily pretreated patients with
      recurrent ovarian cancer. METHODS: The records of patients with recurrent
      epithelial ovarian cancer who were treated with weekly topotecan after failure of
      > or =1 prior regimen were reviewed. Patients received topotecan (median starting
      dose approximately 2.5 mg/m(2)) on days 1, 8, and 15 of a 28-day cycle. Antitumor
      response was assessed after 2 cycles by serial CA-125 levels. RESULTS: Thirty
      five heavily pretreated patients received a mean of 5 cycles of topotecan (range,
      1-13 cycles). Thirty-two patients had definable platinum sensitivity (16
      sensitive, 8 resistant, 8 refractory). Median age was 56 years. A total of 177
      cycles (534 weeks) of topotecan was administered. Hematologic toxicity was
      generally mild, and no grade 4 toxicities were observed. Grade 3 hematologic
      toxicity, including leukopenia, neutropenia, thrombocytopenia, and anemia, was
      observed in 2, 2, 1, and 0 patients, respectively. No patients experienced grade
      3 or 4 nonhematologic toxicity. Based on serial CA-125 measurements, there were 1
      (3%) complete and 5 (15%) partial responses, with 1 of the partial responses in a
      patient with platinum-refractory disease. Stable disease was reported in 13 (38%)
      patients, including 5 patients with platinum-resistant/refractory disease.
      CONCLUSION: Weekly topotecan demonstrates activity and is well tolerated compared
      with historical data with the standard 5-day schedule. Higher doses may be
      warranted because of the high tolerability shown for weekly topotecan. Weekly
      topotecan may be an appropriate treatment option for patients with recurrent
      ovarian cancer, especially heavily pretreated patients who might require dosing
      schedules with improved tolerability.

PMID- 15992917
TI  - Adult granulosa cell tumors of the ovary in two first-degree relatives.
AB  - BACKGROUND: Known inherited mutations are responsible for approximately 10% of
      all epithelial ovarian cancers; however, prior to this report, sex cord-stromal
      ovarian tumors had not been documented in related females. CASE: We report here
      on a mother and daughter, each diagnosed with rare, adult-type granulosa cell
      tumors of the ovary. CONCLUSION: This novel report of granulosa cell tumors
      occurring in two first-degree relatives must be examined with reserve. No
      familial tendency has previously been documented, and our finding may be
      coincidental. However, if additional cases are reported and future research is
      undertaken, biological markers and inherited mutations for certain sex cord
      stromal ovarian tumors may be identified. These advances could lead to targeted
      therapy and specific surveillance protocols with appropriate surgical
      interventions for high-risk patients.

PMID- 15992918
TI  - The expression of Ki-67, p53, estrogen and progesterone receptors affecting
      survival in uterine leiomyosarcomas. A clinicopathologic study.
AB  - OBJECTIVES: To evaluate the level of expression of estrogen receptor (ER),
      progesterone receptor (PR), p53 and Ki-67 in patients with leiomyosarcoma and to
      investigate the effect of these and to identify the clinical parameters on
      prognosis. MATERIALS AND METHODS: Twenty-four patients operated for LMS of
      uterine origin between 1994 and 2003 at Istanbul Medical School, Department of
      Obstetrics and Gynecology and Division of Gynecologic Oncology constituted our
      study group. The data of all patients were updated via mail or phone. The effects
      of stage, grade, chemotherapy, radiotherapy, number of mitoses, presence of
      necrosis, Ki-67 and p53 expression, presence of estrogen and progesterone
      receptors on survival were evaluated. RESULTS: The mean follow-up period of
      patients is 30.42 +/- 25.15 months. The mean overall survival for all LMS
      patients was estimated to be 48.4 +/- 10.38 months. The cumulative survival ratio
      in the 33rd month was 33.08. Age, menopausal status, history of prior
      radiotherapy, number of mitoses had no statistically significant effect on
      overall survival in our study although stage had a significant effect. Finding of
      greater than 10% steroid receptor expression has a positive effect on survival
      ([ER P = 0.019; log rank = 5.49] and [PR P = 0.023; log rank = 5.14]). The median
      value of Ki-67 was calculated to be 30. There was a survival advantage in
      patients with Ki-67 expression (P = 0.034; log rank = 4.49) below the median
      value. p53 levels had no significant effect on survival (P = 0.336; log rank =
      0.92). CONCLUSION: Surgical staging is an important prognostic factor in LMS
      patients, while number of mitoses and grade of the tumor also seem to affect
      prognosis. Contrary to the current literature, our findings suggest that estrogen
      and progesterone receptor positivity greater than 10% may be associated with a
      better prognosis.

PMID- 15992919
TI  - Extraskeletal myxoid chondrosarcoma: a report of a gynecologic case.
AB  - BACKGROUND: Extraskeletal myxoid chondrosarcoma is a rare tumor that has been
      reported and discussed in neurosurgical, orthopedic, and otolaryngologic
      literature. We report a case of vulvar extraskeletal myxoid chondrosarcoma. CASE:
      This is a case of a 46-year-old woman who presented with a soft tissue mass in
      the left vulva and underwent local excision. Grossly, the tumors appeared to be
      leiomyomas. Pathology revealed an extraskeletal myxoid chondrosarcoma.
      CONCLUSION: We report the first case of an extraskeletal myxoid chondrosarcoma
      arising in the vulva.

PMID- 15992920
TI  - The relationship between maternal attitudes and young people's attitudes toward
      children's rights.
AB  - Relations between maternal socio-political attitudes and parenting style and
      young people's and mothers' attitudes toward young people's nurturance and self
      determination rights were examined. Both young people (n = 121) and mothers (n =
      67) were more supportive of nurturance than self-determination rights, although
      young people were more supportive than their mothers of self-determination rights
      and mothers were more supportive than young people of nurturance rights. Maternal
      conservatism was unrelated to young people's support for rights and negatively
      related to mothers' support for both types of rights. Last, young people who
      perceived their mother to be either authoritarian or uninvolved showed stronger
      endorsement of self-determination rights than young people who perceived their
      mother to be authoritative. The implications of these findings for the
      development of young people's attitudes toward rights within the context of
      various family factors are discussed. In particular, it is suggested that a
      balance needs to be achieved between assertion of rights and a respect for the
      rights of others.

PMID- 15992921
TI  - Antifungal coating by biofunctionalized polyelectrolyte multilayered films.
AB  - The surface of medical devices is a common site of bacterial and fungal adhesion,
      first step to the constitution of a resistant biofilm leading frequently to
      chronic infections. In order to prevent such complications, several physical and
      chemical modifications of the device surface have been proposed. Here, we
      experiment a new type of topical antifungal coating using the layer-by-layer
      technique. The nanometric multilayer film obtained by this technique is
      functionalized by the insertion of a chromogranin A-derived antifungal peptide
      (CGA 47-66, chromofungin). We show that the embedded peptide keeps its antifungal
      activity by interacting with the fungal membrane and penetrating into the cell.
      In vitro studies demonstrate that such an antifungal coating is able to inhibit
      the growth of yeast Candida albicans by 65% and completely stop the proliferation
      of filamentous fungus Neurospora crassa. The cytotoxicity of such a coating was
      also assessed by growing human gingival fibroblasts at its surface. Finally, the
      antifungal coating of poly(methylmethacrylate), a widely used material for
      biomedical devices, is successfully tested in an in vivo oral candidiasis rat
      model. Taken together, these results assessed the functionalized multilayer films
      containing a new potent antifungal non-toxic peptide, as a novel and promising
      technique for local antifungal protection.

PMID- 15992922
TI  - The use of poly(ethylene oxide) for the efficient stabilization of entrapped
      alpha-chymotrypsin in silicone elastomers: a chemometric study.
AB  - The enzyme alpha-chymotrypsin, a model for catalytic proteins, was entrapped in
      different silicone elastomers that were formed via the condensation-cure room
      temperature vulcanization (CC-RTV) of silanol terminated poly(dimethylsiloxane)
      with tetraethyl orthosilicate as a crosslinker, in the presence of different
      poly(ethylene oxide) oligomers that were functionalized with triethoxysilyl
      groups. The effects of various chemical factors on both the activity and
      entrapping efficiency of proteins (leaching) were studied using a 2-level
      fractional factorial design--a chemometrics approach. The factors studied include
      the concentration and chain length of poly(ethylene oxide), enzyme content, and
      crosslinker (TEOS) concentration. The study indicated that poly(ethylene oxide)
      can stabilize the entrapped alpha-chymotrypsin in silicone rubber: the specific
      activity can be maximized by incorporating a relatively high content of short
      chain, functional PEO. Increased enzyme concentration was found to adversely
      affect the specific activity. The effect of TEOS was found to be insignificant
      when PEO was present in the elastomer, however, it does affect the activity
      positively in the case of simple elastomers.

PMID- 15992923
TI  - A comparative study of calcium phosphate formation on bioceramics in vitro and in
      vivo.
AB  - Formation of calcium phosphate (Ca-P) on various bioceramic surfaces in simulated
      body fluid (SBF) and in rabbit muscle sites was investigated. The bioceramics
      were sintered porous solids, including bioglass, glass-ceramics, hydroxyapatite,
      alpha-tricalcium phosphate and beta-tricalcium phosphate. The ability of inducing
      Ca-P formation was compared among the bioceramics. The Ca-P crystal structures
      were identified using single-crystal diffraction patterns in transmission
      electron microscopy. The examination results show that ability of inducing Ca-P
      formation in SBF was similar among bioceramics, but considerably varied among
      bioceramics in vivo. Sintered beta-tricalcium phosphate exhibited a poor ability
      of inducing Ca-P formation both in vitro and in vivo. Octacalcium phosphate (OCP)
      formed on the surfaces of bioglass, A-W, hydroxyapatite and alpha-tricalcium
      phosphate in vitro and in vivo. Apatite formation in physiological environments
      cannot be confirmed as a common feature of bioceramics.

PMID- 15992924
TI  - Substance P released from sensory nerve endings influences tear secretion and
      goblet cell function in the rat.
AB  - The aim of this study was to present morphological and functional evidence to
      evaluate whether tear secretion is influenced by neuropeptides released from
      sensory nerve endings of the conjunctiva. Following unilateral electrical
      stimulation of the trigeminal ganglion, tears were collected at both sides and
      assessed for volume and protein concentration; as well as gel electrophoresis and
      luminol chemiluminescence with immunostaining to immunoglobulin A and lysozyme
      measurements. Goblet cell density (goblet cells/100 basal cells) was recorded
      during histopathological examination of removed lids. Rats were pretreated with
      atropine to block parasympathetic; guanethidine to block sympathetic neuronal
      pathways; or hexamethonium to block synaptic transmission in ganglia. Capsaicin
      was used to deplete neurotransmitters from sensory nerve endings or SR140333 to
      block substance P tachykinin NK1 receptor mediated responses. Effects of
      inadequate electrode position or incidental lesion of trigeminal ganglion were
      examined by placing the electrode in false position, or no stimulation at a
      correct position. Electrical stimulation resulted in 380% increase of tear
      secretion (p < 0.001) and 30% decrease of goblet cell density (p < 0.001) on the
      the stimulated side compared to the unstimulated side. Atropine, guanethidine and
      hexamethonium pretreatments had no effect (p > 0.05), but capsaicin and SR140333
      inhibited the effect of stimulation (by 96% and 72%, respectively, p < 0.001).
      Inadequate stimulation did not increase the tear secretion (p < 0.05). Protein
      concentration decreased, whilst tear volume and total secreted protein increased
      (p < 0.005) after stimulation. Electrophoresis showed no difference in protein
      pattern between stimulated and control side and analysis of equivalent amount of
      tear protein with luminol chemiluminescence indicated no difference in
      immunoglobulin A and lysozyme ratio following stimulation (p>0.05). We conclude
      that antidromic electrical activation of conjunctival sensory nerve endings
      significantly increases water, mucus and protein phases of tear. It is suggested
      that the sensory neuropeptide substance P plays a pivotal role in this neurogenic
      regulatory mechanism.

PMID- 15992925
TI  - Decursin and PDBu: two PKC activators distinctively acting in the megakaryocytic
      differentiation of K562 human erythroleukemia cells.
AB  - Protein kinase C (PKC) plays an important role in the proliferation and
      differentiation of various cell types including normal and leukemic hematopoietic
      cells. Phorbol 12,13-dibutyrate (PDBu) induces the megakaryocytic differentiation
      of K562 human erythroleukemia cells through PKC activation. Decursin, a
      pyranocoumarin from Angelica gigas, exhibits the cytotoxic effects on various
      human cancer cell lines and in vitro PKC activation. We report here the
      differences between two PKC activators, tumor-suppressing decursin and tumor
      promoting PDBu, in their actions on the megakaryocytic differentiation of K562
      cells. First of all, decursin inhibited PDBu-induced bleb formation in K562
      cells. Decursin also inhibited the PDBu-induced megakaryocytic differentiation of
      K562 cells that is characterized by an increase in substrate adhesion, the
      secretion of granulocyte/macrophage colony stimulating factor (GM-CSF) and
      interleukin-6 (IL-6), and the surface expression of integrin beta3. The binding
      of PDBu to PKC was competitively inhibited by decursin. Decursin induced the more
      rapid down-regulation of PKC alpha and betaII isozymes than that induced by PDBu
      in K562 cells. Unlike PDBu, decursin promoted the translocation of PKC alpha and
      betaII to the nuclear membrane. Decursin-induced faster down-regulation and
      nuclear translocation of PKC alpha and betaII were not affected by the presence
      of PDBu. All these results indicate that decursin and phorbol ester are PKC
      activators distinctively acting in megakaryocytic differentiation and PKC
      modulation in K562 leukemia cells.

PMID- 15992926
TI  - Effects of catholyte conditioning on electrokinetic extraction of copper from
      mine tailings.
AB  - Effect of electrokinetic treatment on copper partitioning and distribution in
      mine tailings were studied. In particular the effects of catholyte enhancement by
      HAc-NaAc, HCl, HAc-NaAc+EDTA and lactic acid+NaOH were evaluated. The results
      show that conditioning the catholyte plays a very important role in improving Cu
      removal. When HAc-NaAc is used in the catholyte, the removal percentage of total
      Cu from the mine tailings sample reached 12.3% under 40 V in 15 days of
      treatment. The removal percentage of Cu increased to 31.2% when EDTA was used
      together with HAc-NaAc in the catholyte. At the same time, increasing the applied
      voltage and treatment time result in an increase in the Cu removal from the mine
      tailings. Compared with HAc-NaAc (pH=3.52), the use of lactic acid+NaOH (pH=3.15)
      in the catholyte resulted in better performance in Cu removal from the mine
      tailings. HCl treatment resulted in removal of about 17.5% of Cu from the mine
      tailings; however, it resulted in production of significant amounts of toxic
      chlorine gas. Copper partitioning in the mine tailings was analyzed before and
      after the electrokinetic treatments. The analysis was conducted using 0.25 mol/l
      MgCl2 and 0.5 mol/l HCl as extractants, consequently, to assess the mobility of
      Cu after treatment. The results showed that lowering the pH of the mine tailings
      increased the exchangeable Cu fraction (or the portion extracted by MgCl2).
      Accordingly, further acidification results in an increased mobility of Cu and
      increase in the environmental risk of mine tailings.

PMID- 15992927
TI  - Contamination of polycyclic aromatic hydrocarbons (PAHs) in urban soils in
      Beijing, China.
AB  - Soil contamination with polycyclic aromatic hydrocarbons (PAHs) is an increasing
      problem in many countries, including China. An extensive and systematic survey
      has been undertaken to evaluate the contamination with PAHs of urban soils in
      Beijing, China. Soil samples were collected from campuses of universities,
      schools and kindergartens, public squares, fallow land and roadsides, and were
      analyzed for 16 PAHs by GC-MS. There was a high variability in the total PAHs
      (SigmaPAHs) concentrations, ranging from less than 366 to 27,825 ng g(-1). The
      highest SigmaPAHs concentrations were found at roadsides and industrial sites.
      Soil organic carbon (SOC) is one of the important factors that can influence the
      concentrations of PAHs in soils. It was found that concentrations of SigmaPAHs
      were significantly correlated with that of soil organic carbon. To trace the
      sources of PAHs, the ratios of phenanthrene to anthracene and fluoranthene to
      pyrene were used to identify pyrogenic and petrogenic sources, respectively. In
      most cases, PAHs in soils in urban areas of Beijing were pyrogenic. These sources
      included motor vehicle exhausts, industrial activities and coal burning. These
      data can be further used to assess the health risk associated with soils polluted
      with PAHs.

PMID- 15992928
TI  - Assessment of marine pollution in Izmir Bay: nutrient, heavy metal and total
      hydrocarbon concentrations.
AB  - Izmir Bay (western Turkey) is one of the great natural bays of the Mediterranean.
      Izmir is an important industrial and commercial centre and a cultural focal
      point. The main industries in the region include food processing, oil, soap and
      paint production, chemical industries, paper and pulp factories, textile
      industries and metal processing. The mean concentrations showed ranges of 0.01
      0.19 and 0.01-10 microM for phosphate, 0.10-1.8 and 0.12-27 microM for
      nitrate+nitrite, and 0.30-5.8 and 0.43-39 microM for silicate in the outer and
      middle-inner bays, respectively. The TNO(x)/PO(4) ratio is significantly lower
      than the Redfield's ratio and nitrogen is the limiting element in the middle
      inner bays. Diatoms and dinoflagellates were observed all year around in the bay
      and are normally nitrogen limited. Metal concentrations ranged between Hg: 0.05
      1.3, Cd: 0.005-0.82, Pb: 14-113 and Cr: 29-316 microg g(-1) in the sediments. The
      results showed significant enrichments during sampling periods from Inner Bay.
      Outer and middle bays show low levels of heavy metal enrichments except estuary
      of Gediz River. The concentrations of Hg, Cd and Pb in the outer bay were
      generally similar to the background levels from the Mediterranean. The levels
      gradually decreased over the sampling period. Total hydrocarbons concentrations
      range from 427 to 7800 ng g(-1) of sediments. The highest total hydrocarbon
      levels were found in the inner bay due to the anthropogenic activities, mainly
      combustion processes of traffic and industrial activities. The concentrations of
      heavy metals found in fish varied for Hg: 4.5-520, Cd: 0.10-10 and Pb: 0.10-491
      microg kg(-1) in Izmir Bay. There was no significant seasonal variation in metal
      concentrations. An increase in Hg concentration with increasing length was noted
      for Mullus barbatus. A person can consume more than 2, 133 and 20 meals per week
      of fish in human diet would represent the tolerable weekly intake of mercury,
      cadmium and lead, respectively, in Izmir Bay. Heavy metal levels were lower than
      the results in fish tissues reported from polluted areas of the Mediterranean
      Sea.

PMID- 15992929
TI  - Indoleamine 2,3-dioxygenase (IDO) activity is lower in atopic than in non-atopic
      individuals and is enhanced by environmental factors protecting from atopy.
AB  - Tryptophan catabolism activated by the indoleamine 2,3-dioxygenase (EC
      1.13.11.42) (IDO) enzyme in antigen presenting cells has a central role in
      induction of mechanisms suppressing T cell activation or clonal expansion. There
      is evidence suggesting that IDO activity is mainly upregulated by typical Th1
      differentiating signals such as interferon-gamma and bacterial lipopolysaccharide
      (LPS). Therefore, we hypothesized that IDO activity would be lower in a Th2
      associated disease such as atopy and that it would be higher in the presence of
      environmental factors known to favor Th1 differentiation. Here we show that this
      was the case. Concentrations of tryptophan (trp) and kynurenine (kyn), the main
      metabolite, were determined by reverse phase liquid chromatography from serum
      samples of a cohort of 392 non-asthmatic individual of whom 149 were atopics (one
      or more positive skin test when tested with a panel of 22 allergens). Kyn/trp
      ratio, as an indicator of IDO activity, was significantly lower in atopic than in
      non-atopic individuals. The cohort was stratified according to two known atopy
      protecting factors, presence of antibodies against Helicobacter pylori or
      anamnestic information about childhood on a farm environment. As expected, IDO
      activity was significantly higher in their presence than absence.

PMID- 15992930
TI  - Is there any specific association between respiratory viruses and bacteria in
      acute otitis media of young children?
AB  - BACKGROUND: Respiratory viral infections are usually preceding or coinciding with
      acute otitis media (AOM) in children. It is not known if a given viral infection
      would facilitate invasion of bacterial pathogens into the middle ear in a species
      specific way. We reanalysed the microbiological results of the two prospective
      Finnish Otitis Media (FinOM) studies for this purpose. METHODS: The children had
      been followed from 2 months to 2 years of age in specific study clinics and all
      referred AOM events were analysed. Combined results of virus detection tests from
      middle ear fluid and nasopharyngeal aspirate and those of bacterial culture from
      middle ear fluid were cross-tabulated for 529 AOM events in the FinOM Cohort
      Study and for 364 events in the FinOM Vaccine Trial. RESULTS: In both studies the
      main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae
      and Moraxella catarrhalis while the main viruses detected were rhinoviruses and
      respiratory syncytial virus (plus enteroviruses in the Vaccine Trial). No
      distinct species-specific associations were observed between the viral and
      bacterial findings. CONCLUSION: We did not find support to the theory that
      respiratory infection caused by a given viral species would favour growth of a
      certain bacterial pathogen in the MEF more than another.

PMID- 15992931
TI  - A case of persistent Bacillus pumilis bacteremia associated with cholangitis.

PMID- 15992932
TI  - Initiation of antiretroviral therapy in advanced AIDS with active tuberculosis:
      clinical experiences from Thailand.
AB  - OBJECTIVES: To study treatment outcomes of antiretroviral therapy (ART) initiated
      in advanced HIV-infected patients with active tuberculosis (TB). METHODS: A
      retrospective cohort study was conducted in ART-naive HIV-infected patients who
      presented with active TB, CD4<200 cells/microl, and had been initiated ART. ART,
      TB treatment and treatment outcomes of both HIV and TB were studied. RESULTS:
      There were 29 patients (19 males) with a median age of 37 (range 26-65) years.
      Site of TB were: lung (70%), lymph node (27.6%), and gastrointestinal tract
      (3.4%). At the time of TB diagnosis, median (range) CD4 cell count and HIV RNA
      were 74 (23-178) cells/microl and 229,000 (26,100-750,000) copies/ml,
      respectively. All patients received isoniazid, rifampin, ethambutol, and
      pyrazinamide in the first 2 months of TB therapy but the continuation phase was
      different depending on whether efavirenz (EFV) or nevirapine (NVP) was used. ART
      was initiated at a median of 8 weeks of TB treatment. All patients received NNRTI
      based regimens (EFV 62.1%, NVP 37.9%). Percentage of patients with HIV RNA<50
      copies/ml at 24 and 48 weeks of ART was 65.5 and 75.9%. Median CD4 cell count at
      24, 48, and 72 weeks were 156, 186, and 227 cells/microl, respectively. Eighteen
      patients were cure; eight were treatment completed; two were treatment
      interrupted; and one died from CMV encephalitis. There was neither occurrence of
      new OI or relapse of TB in 26 patients who completed 72-week follow-up.
      CONCLUSIONS: Initiation of ART with NNRTI-based regimens at 4-12 weeks of TB
      treatment in advanced AIDS may be safe and effective, and may not be delayed.
      Further, prospective clinical studies for the optimal timing of ART initiation
      and ART regimen are needed.

PMID- 15992933
TI  - GFP-reporter for a high throughput assay to monitor estrogenic compounds.
AB  - In vitro test systems using yeast cells are a useful tool for the determination
      of the estrogenic activity of estrogens, phyto- and xeno-estrogens and can be
      used for monitoring large sample numbers in a routine analysis procedure. Our
      conventional transactivation assay functions with an expression plasmid
      expressing estrogen receptor alpha (ERalpha) under the control of a copper
      inducible CUP1 promoter and a reporter plasmid expressing beta-galactosidase
      under the control of the vitellogenin estrogen response element (ERE). In the
      novel yeast screen system the lacZ gene in the reporter plasmid was substituted
      by a gene for green fluorescent protein (GFP). Incubation of yeast with various
      concentrations of estrogenically active substances led to expression of the
      reporter gene product GFP in a dose dependent manner. The yeast transactivation
      assay was further down-scaled to be performed in a microplate scale, which is an
      important step to facilitate handling of large sample numbers. The sensitivity
      and reproducibility of the novel test system could be confirmed by analysis of
      the potencies of various estrogenically active substances. Thus, the newly
      developed yeast estrogen screen using GFP as a reporter can substitute the assay
      that has been used for a period of several years.

PMID- 15992934
TI  - Molecular tools to study melatonin pathways and actions.
AB  - Melatonin, an indoleamine neurohormone that is synthesized mainly in the pineal
      gland and derived from 5-HT, has many effects on a wide range of physio
      pathological functions. Some of these effects are mediated by the interactions of
      melatonin with the two melatonin MT1 and MT2 receptors. Other effects are often
      suggested to be due to the chemical antioxidant nature of this indoleamine, and
      are observed at high, non-physiological concentrations. However, it is
      increasingly believed that some of these effects are due to interactions with
      other protein targets. In this review, we summarize the molecular pharmacology of
      melatonin, including the main enzymes involved in its synthesis and catabolism,
      and the proteins that mediate its actions. Furthermore, various compounds, mainly
      inhibitors and antagonists, that can be used to dissect these functions and
      pathways are presented.

PMID- 15992935
TI  - Cannabinoid CB1 receptors control conditioned drug seeking.
AB  - Recent developments have implicated cannabinoid CB1 receptors as a novel target
      for a new class of therapeutic agents used to treat drug addiction. CB1 receptors
      are expressed in the motivational circuitry of the brain and modulate drug
      seeking. Blockade of the CB1 receptor is particularly effective in reducing cue
      induced reinstatement of drug seeking, an animal analogue of cue-induced relapse
      in human addicts. These relapse-preventing properties are observed with different
      classes of abused drug (i.e. psychostimulants, opiates, nicotine and alcohol). In
      addition, recent evidence indicates a more general role of CB1 receptors in
      reward-related memories, which is consistent with the proposed role of
      endocannabinoids in memory-related plasticity. Relapse-preventing actions and
      inhibitory effects on weight gain were confirmed recently in clinical trials with
      the CB1 antagonist rimonabant. Collectively, these clinical and preclinical
      studies suggest that antagonists of CB1 receptors offer a novel approach in the
      treatment of addictive behaviours.

PMID- 15992936
TI  - Purification and serological analyses of tospoviral nucleocapsid proteins
      expressed by Zucchini yellow mosaic virus vector in squash.
AB  - A plant viral vector engineered from an in vivo infectious clone of Zucchini
      yellow mosaic virus (ZYMV) was used to express the nucleocapsid proteins (NPs) of
      tospoviruses in planta. The open reading frames (ORFs) of NPs of different
      serogroups of tospoviruses, including Tomato spotted wilt virus, Impatiens
      necrotic spot virus, Watermelon silver mottle virus, Peanut bud necrosis virus,
      and Watermelon bud necrosis virus (WBNV), were in frame inserted in between the
      P1 and HC-Pro genes of the ZYMV vector. Six histidine residues and an NIa
      protease cleavage site were added at the C-terminal region of the inserts to
      facilitate purification and process of free form of the expressed NPs,
      respectively. Approximately 1.2-2.5 mg/NPs 100 g tissues were purified from leaf
      extracts of zucchini squash. The expressed WBNV NP was used as an immunogen for
      the production of highly specific polyclonal antisera and monoclonal antibodies.
      The procedure provides a convenient and fast way for production of large
      quantities of pure NPs of tospoviruses in planta. The system also has a potential
      for production of any proteins of interest in cucurbits.

PMID- 15992937
TI  - Discriminating between serological responses to European-genotype live vaccine
      and European-genotype field strains of porcine reproductive and respiratory
      syndrome virus (PRRSV) by peptide ELISA.
AB  - A peptide ELISA was developed based on an immunodominant and hypervariable
      epitope in the ORF4 envelope glycoprotein of porcine reproductive and respiratory
      syndrome virus (PRRSV). The peptide sequence was derived from the Porcilis live
      attenuated PRRSV vaccine strain (genotype 1, European). Antibodies induced by the
      field PRRSVs currently circulating in Poland were not detected by the Porcilis
      ORF4 peptide ELISA. In contrast, Porcilis-vaccinated animals seroconverted in the
      ORF4 peptide ELISA at 21 days post-vaccination. Maximal titers were seen 30-92
      days post-vaccination; most sera had endpoint titers between 1:1000 and
      1:100,000. In a paired format, where sera were assayed in two separate ELISAs
      using ORF4 peptides derived from the genetically very closely related Porcilis
      and Lelystad PRRSV strains, it was possible to differentiate between antibodies
      induced by these two viruses. The Porcilis and Lelystad ORF4 peptide ELISAs had
      sensitivities of 89 and 100%, respectively. Thus, ORF4 peptide ELISA afforded
      specific detection of antibodies induced by an European-genotype live-attenuated
      vaccine PRRSV strain (Porcilis). The results suggest that specific ORF4 peptide
      ELISAs can be custom-made for European-genotype PRRSV strains, using general
      peptide design criteria described in this work. Thus, ORF4 ELISAs may be
      generally useful, to monitor safety and operational aspects of European-genotype
      live-attenuated PRRSV vaccine virus use in populations with circulating field
      European-genotype PRRSVs.

PMID- 15992938
TI  - Spectroscopic analysis of Kaposi's sarcoma-associated herpesvirus infected cells
      by Raman tweezers.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human
      herpesvirus-8 (HHV-8), is a tumor causing virus. KSHV is the cause of several
      disease conditions known as Kaposi's sarcoma, multicentric Castleman disease, and
      primary effusion lymphoma. Cell culture supernatants from KSHV infected
      hematopoietic cells induced angiogenic tubule formation to a significantly
      greater extent than uninfected hematopoietic cells. Raman spectrum profiles were
      generated to differentiate the uninfected from KSHV infected cells. In general,
      profiles from all the hematopoietic cells shared similar peaks; however, the
      relative abundance of specific components varied significantly between the cells.
      Subsequent use of the multivariate analysis of the Raman spectra revealed
      significant differences between the uninfected and the KSHV infected cells. Taken
      together, this study reports the use of Raman tweezers to distinguish and analyze
      the biological relevance of KSHV infected cell signaling.

PMID- 15992939
TI  - Determination of photosynthetic and enzymatic biomarkers sensitivity used to
      evaluate toxic effects of copper and fludioxonil in alga Scenedesmus obliquus.
AB  - Modulated PAM fluorometry and Plant Efficiency Analyser methods were used to
      investigate photosynthetic fluorescence parameters of alga Scenedesmus obliquus
      exposed to inhibitory effect of fungicides copper sulphate and fludioxonil (N-(4
      nitrophenyl)-N'-propyl-uree). The change of those parameters were studied when
      alga S. obliquus have been exposed during 48 h to different concentrations of
      fungicides (1, 2 and 3 mgl(-1)). Under the same condition, enzymatic activities
      of catalase, ascorbate peroxidase, glutathione reductase and glutathione S
      transferase were investigated to evaluate antioxidative response to fungicides
      effects. The change of sensitivity of those parameters was dependent to the mode
      of fungicide action, their concentration and time of exposure. For copper
      effects, the most indicative photosynthetic biomarkers were parameters Q(N) as
      non-photochemical fluorescence quenching, Q(Emax) as the proton induced
      fluorescence quenching and ABS/RC as the antenna size per photosystem II reaction
      center. Copper induced oxidative stress was indicated by increased activity of
      catalase serving as the most sensitive and valuable enzymatic biomarker. On the
      other hand, fludioxonil effect on photosynthetic parameters was very negligible
      and consequently not very useful as biomarkers. However, fludioxonil induced
      strong antioxidative activities associated with cytosol enzymes, as we found for
      catalase, ascorbate peroxidase and glutathione S-transferase activities. By
      obtained results, we may suggest for the activation of those enzymes to be
      sensitive and valuable biomarkers of oxidative stress induced by fludioxonil.
      Determination of biomarkers sensitivity may offer advantages in providing real
      criteria to use them for ecotoxicological diagnostic studies.

PMID- 15992940
TI  - Teratogenic effects of two antifungal triazoles, triadimefon and triadimenol, on
      Xenopus laevis development: craniofacial defects.
AB  - Triadimefon and triadimenol, fungicides used in agriculture, are suspected of
      producing craniofacial malformations. As the results of FETAX analysis showed
      that Triadimefon was highly teratogenic, we studied the action of these triazoles
      on the development of the branchial apparatus in Xenopus, using early molecular
      markers and analysis of the cartilaginous-muscular elements of tadpoles.
      Teratogenic effects were observed, after exposure at the neurula stage, at the
      level of cartilages and muscles of the 1st and 2nd branchial arches. By in situ
      hybridization, we observed that in exposed specimens the territories of the
      branchial arches are perturbed. From these results, we considered the
      craniofacial malformations related to the influence of triazoles on the
      differentiation of branchial arches. Comparing the anomalies caused by triazoles
      and by retinoic acid (RA) led us to the conclusion that triazoles can affect
      endogenous RA content, as has been shown for mammals.

PMID- 15992941
TI  - Profiling of gender-regulated gene transcripts in the filarial nematode Brugia
      malayi by cDNA oligonucleotide array analysis.
AB  - Microarray technology permits high-throughput comparisons of gene expression in
      different parasite stages or sexes and has been used widely. We report the first
      use of this technology for analysis of gene expression in filarial male and
      female worms. The slide array (comprised of 65-mer oligos representing 3569 EST
      clusters) was spotted with sequences selected from the extensive Brugia malayi
      EST database (). Arrays were hybridized with Cy dye labeled male and female cDNA.
      The experimental design included both biological and technical (dye-flip)
      replicates. The data were normalized for background and probe intensity, and the
      relative abundance of hybridized cDNA for each spot was determined. Genes showing
      two-fold or greater differences with P<0.05 were considered gender-regulated
      candidates. One thousand one hundred and seventy of 2443 clusters (48%) with
      signals above threshold in at least one sex were considered as gender-regulated
      gene candidates. This included 520 and 650 clusters up-regulated in male and
      female worms, respectively. Fifty of 53 (94%) gender-regulated candidate genes
      identified by microarray analysis were confirmed by real-time RT-PCR.
      Approximately 61% of gender-regulated genes had significant similarity to known
      genes in other organisms such as Caenorhabditis elegans. Many C. elegans
      homologues of these genes have been reported to have reproductive phenotypes
      (sterility or abnormal embryo development) by RNA interference. This study has
      provided the first broad view of gender-regulated gene expression in B. malayi;
      this should lead to improved understanding of reproduction in filarial nematodes.
      More generally, this approach holds great promise as a means of studying stage
      specific or tissue-specific gene expression in parasitic nematodes.

PMID- 15992942
TI  - Different localization in rat brain of the novel cytosolic ketone body-utilizing
      enzyme, acetoacetyl-CoA synthetase, as compared to succinyl-CoA:3-oxoacid CoA
      transferase.
AB  - In lipogenic tissue cytosol, ketone bodies are known to be activated by
      acetoacetyl-CoA synthetase (AACS) and incorporated into cholesterol and fatty
      acids. In order to investigate the physiological role of AACS in the brain, we
      examined the localization of AACS mRNA in rat brain by in situ hybridization
      using a labeled probe. High labeling was observed in the midbrain, pons/medulla,
      cerebral cortex, hippocampus and cerebellum, and the localization profile of AACS
      mRNA was different from that of succinyl-CoA:3-oxoacid CoA-transferase (SCOT), a
      mitochondrial ketone body-activating enzyme. In addition, the expression of AACS
      mRNA in the cerebellum was restricted primarily to glial cells, while in the
      cerebral cortex, it was restricted to neuronal cells. Streptozotocin treatment
      caused remarkable decreases in AACS mRNA levels in all regions where expression
      was observed, but changes in SCOT mRNA levels were not observed. These results
      suggest that the physiological role of AACS is different from that of SCOT and
      varies depending upon its localization in the brain.

PMID- 15992943
TI  - Fluorescence methods to detect phase boundaries in lipid bilayer mixtures.
AB  - Phase diagrams of lipid mixtures can show several different regions of phase
      coexistence, which include liquid-disordered, liquid-ordered, and gel phases.
      Some phase regions are small, and some have sharp boundaries. The identity of the
      phases, their location in composition space, and the nature of the transitions
      between the phases are important for understanding the behavior of lipid
      mixtures. High fidelity phase boundary detection requires high compositional
      resolution, on the order of 2% compositional increments. Sample artifacts,
      especially the precipitation of crystals of anhydrous cholesterol, can occur at
      higher cholesterol concentrations unless precautions are taken. Fluorescence
      resonance energy transfer (FRET) can be used quantitatively to find the phase
      boundaries and even partition coefficients of the dyes between coexisting phases,
      but only if data are properly corrected for non-FRET contributions. Self
      quenching of the dye fluorescence can be significant, distorting the data at dye
      concentrations that intuitively might be considered acceptable. Even more simple
      than FRET experiments, measurements of single-dye fluorescence can be used to
      find phase boundaries. Both FRET and single-dye fluorescence readily detect the
      formation of phase domains that are much smaller than the wavelength of light,
      i.e. "nanoscopic" domains.

PMID- 15992944
TI  - Impact of age on in-hospital mortality of surgical patients in a German
      university hospital.
AB  - Although the frequency of major surgical procedures in elderly patients is
      increasing, the impact of age as an independent factor on in-hospital mortality
      and capacity planning is uncertain. Therefore, we analyzed how age, gender,
      number of diagnoses, and number of operations per patient are reflecting the
      demographic changes going on in the last decade. Furthermore, we analyzed the
      influence of age, main diagnoses, and comorbidities on in-hospital mortality, and
      cost factors, like duration of in-hospital stay, number of operations, and stay
      at the intensive care unit using multiple regression analysis. One thousand four
      hundred and sixty-nine patients hospitalized in 1990, and 5,718 patients
      hospitalized during 1998-2000 at the surgical department of a German university
      hospital were recruited. The average age of the patients increased significantly
      from the year 1990 to 1999 (by 4 years). The overall in-hospital mortality of the
      elderly patients (above 70 years of age) declined from 18.6% in 1990 to 7.6% in
      2000. The number of diagnoses increased from 1.27 to 3.5 per patient. Age is a
      significant, independent risk factor for in-hospital mortality (odd's ratio (OR),
      2.2), prolonged stay at intensive care unit (OR, 1.8), reoperation (OR, 1.3), and
      prolonged hospitalization (OR, 1.8). Nevertheless, oncologic diseases and pre
      existing comorbidities are also significant independent factors for the clinical
      course and costs resulting from treating elderly patients. We conclude that
      decisions for surgical treatment should not be solely based on patient's age. The
      demographic changes in Europe result in an over-proportional increase in
      expenditures, which should be included when planning the capacities of a surgical
      department.

PMID- 15992945
TI  - Relationship between self-reported prevalence of diabetes mellitus using the
      Cornell Medical Index (CMI) and prevalence determined by glycosylated hemoglobin
      (HbA(1c)) in an elderly community-dwelling population.
AB  - Reports of diabetes mellitus samples in community-dwelling unselected populations
      suggest a prevalence of 6%. A further 3% of unknown diabetes mellitus subjects
      are suggested when using formal biochemical methods of diagnosis. In this study,
      we present the prevalence of diabetes mellitus by self-reports using the CMI and
      concomitant biochemical detection in 436 community-dwelling older adults who have
      participated in a 20-year-study of age and cognitive performance in Manchester,
      UK. Twenty-three of the group reported that they had diagnosed diabetes mellitus,
      three individuals had a raised HbA(1c) of greater than 7.0% on random testing,
      but no knowledge of having diabetes mellitus. These individuals were re-contacted
      and three said they subsequently had a diagnosis of diabetes mellitus made within
      the two years following the questionnaire. We conclude that in an older
      population of community-dwelling subjects the numbers of undiagnosed cases of
      diabetes mellitus is lower than anticipated, based on large unselected population
      samples. The greater opportunity to interact with health care professionals who
      may consider screening for diabetes mellitus may explain these findings.

PMID- 15992946
TI  - Reversible cardiomyopathy in a patient with juvenile hemochromatosis.

PMID- 15992947
TI  - Atrial septal defect closure in a patient with "irreversible" pulmonary
      hypertensive arteriopathy.
AB  - The presence of irreversible pulmonary hypertension in patients with atrial
      septal defect (ASD) is thought to preclude shunt closure. We report the case of a
      woman with plexiform pulmonary arteriopathy secondary to an ostium secundum ASD
      who was able to successfully undergo percutaneous shunt closure following therapy
      with chronic intravenous prostacyclin (Flolan). One year after closure, the
      patient was weaned off Flolan over a period of 7 months following the institution
      of oral Bosentan therapy. Our case illustrates how aggressive vasodilator therapy
      with prostaglandins may be capable of reducing pulmonary artery pressure and
      permitting shunt closure in a patient once considered to have "inoperable"
      pulmonary arteriopathy.

PMID- 15992949
TI  - Beta-blockade intolerance in anthracycline-induced cardiomyopathy.
AB  - Beta-blockade efficiency and safety in anthracycline induced cardiomyopathy (AIC)
      are poorly documented. Cardiac Heart Failure (CHF) due to an AIC has haemodynamic
      and histologic particularities: only mild ventricular dilatation, restriction
      pattern and myocardial and endocardial fibrous thickening. Therefore, beta
      blockade therapy initiation may cause heart failure decompensation by absence of
      the usual left ventricular adaptation (improvement of left ventricular compliance
      allowing maintenance of stroke volume). We describe an AIC patient in whom a
      first beta-blockade initial administration caused a global cardiac failure; after
      stabilisation, one month later, a second attempt caused a new cardiac failure. We
      raise the question of beta-blockade safety in restrictive cardiomyopathies.

PMID- 15992948
TI  - D-dimer level influences thromboembolic events in patients with atrial
      fibrillation.
AB  - BACKGROUND: Elevated coagulative molecular markers could reflect the
      prothrombotic state in the cardiovascular system of patients with non-valvular
      atrial fibrillation (NVAF). A prospective, cooperative study was conducted to
      determine whether levels of coagulative markers alone or in combination with
      clinical risk factors could predict subsequent thromboembolic events in patients
      with NVAF. METHODS: Coagulative markers of prothrombin fragment 1+2, D-dimer,
      platelet factor 4, and beta-thromboglobulin were determined at the enrollment in
      the prospective study. RESULTS: Of 509 patients with NVAF (mean age, 66.6 +/-
      10.3 years), 263 patients were treated with warfarin (mean international
      normalized ratio, 1.86), and 163 patients, with antiplatelet drugs. During an
      average follow-up period of 2.0 years, 31 thromboembolic events occurred. Event
      free survival was significantly better in patients with D-dimer level < 150 ng/ml
      than in those with D-dimer level>or==150 ng/ml. Other coagulative markers,
      however, did not predict thromboembolic events. Age (>or==75 years),
      cardiomyopathies, and prior stroke or transient ischemic attack were independent,
      clinical risk factors for thromboembolism. Thromboembolic risk in patients
      without the clinical risk factors was quite low (0.7%/year) when D-dimer was <
      150 ng/ml, but not low (3.8%/year) when D-dimer was >or==150 ng/ml. It was
      >5%/year in patients with the risk factors regardless of D-dimer levels. This was
      also true when analyses were confined to patients treated with warfarin.
      CONCLUSIONS: D-dimer level in combination with clinical risk factors could
      effectively predict subsequent thromboembolic events in patients with NVAF even
      when treated with warfarin.

PMID- 15992950
TI  - Strain discrimination among B. anthracis and related organisms by
      characterization of bclA polymorphisms using PCR coupled with agarose gel or
      microchannel fluidics electrophoresis.
AB  - The bclA gene codes for the protein backbone of the exosporium glycoprotein BclA
      of B. anthracis. BclA has a central collagen-like region formed by polymorphic
      GXX repeats and conserved amino- and carboxy-termini. It is noted here that the
      bclA gene is also present in the genome of Bacillus cereus and Bacillus
      thuringiensis. There is considerable size heterogeneity among the BclA proteins,
      both for species and strains, due to different numbers of GPT repeats and
      [GPT]5GDTGTT repeats (BclA repeats). PCR products that included the entire
      variable region were analyzed by conventional agarose gel electrophoresis and by
      micro-channel fluidics (MCF) LabChip to assess differences in molecular weight
      (MW). Both methods provided discrimination at the strain level for B. cereus
      group organisms. Results obtained by MCF electrophoresis were superior to
      conventional agarose gel analysis demonstrating improved reproducibility and much
      faster analysis time. The expression of a carbohydrate-rich exosporium
      (corresponding to BclA) in other members of the B. cereus group, in addition to
      B. anthracis, was also demonstrated ultra-structurally. Analysis of sequence
      variability within the bclA gene CLR revealed even greater potential for strain
      and species identification.

PMID- 15992951
TI  - Laboratory-based simulation of freezing profiles of beef trim for Escherichia
      coli O157 survival determinations.
AB  - This study was undertaken to develop a simple laboratory-based method for
      simulating the freezing profiles of beef trim so that their effect on E. coli
      O157 survival could be better assessed. A commercially available apparatus of the
      type used for freezing embryos, together with an associated temperature logger
      and software, was used for this purpose with a -80 degrees C freezer as a heat
      sink. Four typical beef trim freezing profiles, of different starting
      temperatures or lengths, were selected and modelled as straight lines for ease of
      manipulation. A further theoretical profile with an extended freezing plateau was
      also developed. The laboratory-based setup worked well and the modelled freezing
      profiles fitted closely to the original data. No change in numbers of any of the
      strains was apparent for the three simulated profiles of different lengths
      starting at 25 degrees C. Slight but significant (P<0.05) decreases in numbers (
      approximately 0.2 log cfu g(-1)) of all strains were apparent for a profile
      starting at 12 degrees C. A theoretical version of this profile with a freezing
      plateau phase extended from 11 h to 17 h resulted in significant (P<0.05)
      decreases in numbers ( approximately 1.2 log cfu g(-1)) of all strains. Results
      indicated possible avenues for future research in controlling this pathogen. The
      method developed in this study proved a useful and cost-effective way for
      simulating freezing profiles of beef trim.

PMID- 15992952
TI  - Adaptastat--a new method for optimising of bacterial growth conditions in
      continuous culture: Interactive substrate limitation based on dissolved oxygen
      measurement.
AB  - A new method for continuous cultivation of microbes, called adaptastat, is
      described. It involves automatic adaptation of microbial cultures to their
      maximum feeding rates and avoids substrate accumulation. The state of the culture
      is estimated at intervals by briefly (and markedly) decreasing the substrate
      feeding rate and measuring, via the dissolved oxygen response, the time taken to
      exhaust the residual substrate. The method has been exemplified by cultivating
      Escherichia coli on single carbon sources (glucose, acetate, succinate, and fully
      deuteriated medium based on deuteriated succinate) and also by simultaneous
      limitation of two feeding channels (succinate/acetate and glucose/ammonium
      chloride). Several possible applications of the adaptastat technology are
      presented. The method provides an efficient means of labelling microbial
      components and products with stable isotopes. In particular, adaptastat
      technology can be used to adapt disabled bacterial strains to the use of simple,
      inexpensive substrates. It can also be used more generally in the study of
      microbial cell cultures, for example for the determination of maximum specific
      growth rates and the stoichiometric ratio of utilisation of two nutrients in
      conditions of simultaneous limitation.

PMID- 15992953
TI  - Feasibility of cranio-spinal axis radiation with the Hi-Art tomotherapy system.
AB  - BACKGROUND AND PURPOSE: Helical tomotherapy can eliminate the need for junction
      lines. The goal of this study is to evaluate tomotherapy in the delivery of CSA
      radiation and measurement of plan quality using physical parameters in comparing
      conventional (CSA-RT) and helical tomotherapy (CSA-TOMO) plans. PATIENTS AND
      METHODS: CSA-TOMO and CSA-RT plans were created for dosimetric comparison.
      Integral dose values were calculated. The ratios D50% (dose received by 50% of
      the organ at risk's volume) and D10% (dose received by 10% of the organ at risk's
      volume) were calculated representing large volumes and small volumes of organs at
      risk receiving significant dose. RESULTS: When considering D50% and D10%, CSA
      TOMO has a dosimetric advantage over CSA-RT for most organs at risk. The body
      integral dose was higher for the CSA-TOMO plan by approximately 6.5%.
      CONCLUSIONS: Tomotherapy is a feasible alternative for treatment of CSA. Analysis
      shows that tomotherapy improves dose ratios over conventional radiation for most
      organs at risk. The impact of a small increase in whole body integral dose is
      unknown. Long-term follow-up will be needed to answer this question as others
      have argued of the possibility of increased risk of secondary malignancies due to
      delivery of radiotherapy with IMRT.

PMID- 15992954
TI  - Enhanced prepulse inhibition of startle using salient prepulses in rats.
AB  - Prepulse inhibition (PPI) of the startle reflex occurs when a non-startling
      stimulus is presented shortly prior to the startling stimulus. PPI is an
      operational measure for sensorimotor gating. PPI in humans is enhanced by
      attention, but there is no evidence yet for attentional modulation of PPI in
      animals. We here combined PPI and conditioned inhibition paradigms in order to
      investigate attentional modulation of PPI in rats. PPI was assessed before and
      after training for conditioned inhibition of fear with the conditioned stimulus
      (auditory CS) and conditioned inhibitor (visual CI) as prepulses. The CI
      significantly enhanced PPI after training, whereas presentation of the CS had no
      effect on PPI. These data suggest attentional modulation of PPI in rats by
      biologically salient prestimuli. This new paradigm may be useful for examining
      attentional modulation of PPI in animals and to compare attentional modulation in
      humans and animals.

PMID- 15992955
TI  - Prefrontal cortical cells projecting to the supplementary eye field and
      presupplementary motor area in the monkey.
AB  - We examined the location and spatial distribution of prefrontal cortical (PF)
      cells projecting to the supplementary eye field (SEF) and presupplementary motor
      area (pre-SMA) using a double retrograde-labeling technique in monkeys (Macaca
      fuscata). The SEF and pre-SMA were physiologically identified based on the
      findings of intracortical microstimulation and single cell recordings. Two
      fluorescent tracers, diamidino yellow and fast blue, were injected into the SEF
      and pre-SMA of each monkey. Retrogradely labeled cells in the PF were plotted
      with an automated plotting system. The cells projecting to the SEF and pre-SMA
      were mainly distributed in the upper and lower banks of the principal sulcus
      (area 46), with little overlap. Cells projecting to the SEF, but not to the pre
      SMA, were observed in areas 8a, 8b, 9, 12, and 45. These findings suggest that
      the SEF and pre-SMA receive different sets of information from the PF cells.

PMID- 15992956
TI  - Acetate production from lactose by Clostridium thermolacticum and hydrogen
      scavenging microorganisms in continuous culture--effect of hydrogen partial
      pressure.
AB  - The effect of the addition of hydrogen-consuming microorganisms on the metabolism
      of Clostridium thermolacticum was studied. By growing this bacterium in
      continuous culture at 58 degrees C, on 29 mmol lactose l(-1) (10 gl(-1)) in the
      feed, with the H2-consuming microorganisms Methanothermobacter
      thermoautotrophicus and Moorella thermoautotrophica, the volumetric productivity
      of acetate was increased up to 3.9 mmol l(-1)h(-1) at a dilution rate of 0.058 h(
      1). This was about three times higher than the maximal acetate volumetric
      productivity quantified when C. thermolacticum was cultivated alone. In the
      consortium, C. thermolacticum was the only species able to metabolize lactose; it
      produced not only acetate, but also hydrogen, carbon dioxide and lactate. The
      other species of the consortium were growing on these by-products. Meth.
      thermoautotrophicus played an important role as a very efficient hydrogen
      scavenger and decreased the hydrogen partial pressure drastically: hydrogen was
      converted to methane. Moor. thermoautotrophica converted lactate as well as
      hydrogen and carbon dioxide into acetate. As a consequence, lactose was
      efficiently consumed and the only organic product in the liquid phase was
      acetate.

PMID- 15992957
TI  - Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of
      SARS coronavirus.
AB  - A novel coronavirus (CoV) has recently been identified as the aetiological agent
      of severe acute respiratory syndrome (SARS). Nucleocapsid (N) proteins of the
      Coronaviridae family have no discernable homology, but they share a common
      nucleolar-cytoplasmic distribution pattern. There are three putative nuclear
      localization signal (NLS) motifs present in the N. To determine the role of these
      putative NLSs in the intracellular localization of the SARS-CoV N, we performed a
      confocal microscopy analysis using rabbit anti-N antisera. In this report, we
      show that the wild type N was distributed mainly in the cytoplasm. The N-terminal
      of the N, which contains the NLS1 (aa38-44), was localized to the nucleus. The C
      terminus of the N, which contains both NLS2 (aa257-265) and NLS3 (aa369-390) was
      localized to the cytoplasm and the nucleolus. Results derived from analysis of
      various deletion mutations show that the region containing amino acids 226-289 is
      able to mediate nucleolar localization. The deletion of two hydrophobic regions
      that flanked the NLS3 recovered its activity and localized to the nucleus.
      Furthermore, deletion of leucine rich region (220-LALLLLDRLNRL) resulted in the
      accumulation of N to the cytoplasm and nucleolus, and when fusing this peptide to
      EGFP localization was cytoplasmic, suggesting that the N may act as a shuttle
      protein. Differences in nuclear/nucleolar localization properties of N from other
      members of coronavirus family suggest a unique function for N, which may play an
      important role in the pathogenesis of SARS.

PMID- 15992958
TI  - Cloning and characterization of rat importin 9: implication for its neuronal
      function.
AB  - We describe the structure of the rat importin 9 gene, together with its
      transcripts and the encoded protein with its putative functional domains. The
      importin 9 gene contains 24 exons in a genomic region spanning >52,000 bp. It is
      transcribed into two mRNAs, generated by means of alternative polyadenylation
      site usage arranged in tandem. Both transcripts possess the same noncanonical
      polyadenylation signal (AGUAAA) in rat, this hexamer being conserved in all
      vertebrates examined. Additionally, intron 8 is bordered by AT-AC dinucleotides.
      Importin 9 is expressed throughout adult rat tissues, but the 114-kDa Importin 9
      protein was detected only in the brain. The localization of the Importin 9
      protein was examined by immunohistochemistry in both adult rat tissues and
      primary hippocampal cell cultures. The strongest labeling was detected in vivo in
      areas populated by neurons in high density and also in the dendritic processes
      emanating from these cells. This protein was clearly concentrated in the nuclei
      of these cells, although their cytoplasms too were heavily labeled. Strong
      cytoplasmic and very strong nuclear staining was found in a vast majority of the
      cells with neuronal morphology in vitro. Cultured cells with glial morphology
      generally exhibited a weaker cytoplasmic labeling. In these cells, the signal
      decorated the nuclear envelope without nuclear staining and gradually dwindled
      toward the cell periphery. These results hint at the cell- or tissue-type
      specific functions of this type of importin protein.

PMID- 15992960
TI  - Circadian oscillations of RPCH gene expression in the eyestalk of the crayfish
      Cherax quadricarinatus.
AB  - The RPCH and beta-actin cDNAs from the crayfish Cherax quadricarinatus were
      amplified, cloned and sequenced. The primary structure sequences of these cDNAs
      were compared to other members of the AKH/RPCH family. Fluctuations in the amount
      of the C. quadricarinatus RPCH and beta-actin mRNAs, as cDNAs, were quantified
      every 3h by RT-PCR. Single cosinor analysis supports the notion of beta-actin and
      RPCH mRNA circadian behavior in animals subjected to 12h:12h light/dark regimes.
      In constant darkness RPCH mRNA concentration changes to ultradian cycles.

PMID- 15992959
TI  - Pretreatment vascular endothelial growth factor (VEGF) and matrix
      metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small
      cell lung cancer (NSCLC).
AB  - PURPOSE: In the present study, we investigated the prognostic value of vascular
      endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum
      levels in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS
      AND METHODS: From September 1999 to June 2001, pretreatment serum levels of VEGF
      and MMP-9 were analysed in 194 patients of a randomized phase III trial with
      enzyme-linked immunoassays. RESULTS: Patients with a VEGF serum level higher than
      the median serum level (10,995 pg/ml) had a significantly shorter overall
      survival than those with a lower serum level (P=0.04). The MMP-9 serum level did
      not correlate with survival. In a multivariate Cox regression analysis, only the
      pretreatment serum level of VEGF, the Karnofsky performance status, and the
      presence of bone metastases were identified as independent prognostic factors.
      CONCLUSIONS: The pretreatment VEGF serum level was identified as independent
      prognostic factor in this study and may help to assess individual risk and
      treatment profiles in patients with metastatic NSCLC.

PMID- 15992961
TI  - Activation of the cAMP pathway by variant human MC1R alleles expressed in HEK and
      in melanoma cells.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) activates the melanocortin-1
      receptor (MC1R) on melanocytes to promote a switch from red/yellow pheomelanin
      synthesis to darker eumelanins via positive coupling to adenylate cyclase. The
      human MC1R locus is highly polymorphic with the specific variants associated with
      red hair and fair skin (RHC phenotype) postulated to be loss-of-function
      receptors. We have examined the ability of MC1R variants to activate the cAMP
      pathway in stably transfected HEK293 cells. The RHC associated variants,
      Arg151Cys, Arg160Trp and Asp294His, demonstrated agonist-mediated increases in
      cAMP and phosphorylation of cAMP-responsive element-binding protein (CREB).
      Whereas the Asp294His variant showed severely impaired functional responses, the
      Arg151Cys and Arg160Trp variants retained considerable signaling capacity.
      Melanoma cells homozygous for either the Arg151Cys variant or consensus sequence
      both elicited CREB phosphorylation in response to alpha-MSH in the presence of
      IBMX. The common RHC alleles, Arg151Cys, Arg160Trp and Asp294His, are neither
      complete loss-of-function receptors nor are they functionally equivalent.

PMID- 15992962
TI  - Melanocortinergic control of penile erection.
AB  - Melanocortin receptors in the forebrain and spinal cord can be activated by
      endogenous or synthetic ligands to induce penile erection in rats and human
      subjects. To better understand how melanocortin circuits play a role in sex
      behavior, we review the contribution of melanocortin receptors and/or neurons in
      the hypothalamus, hindbrain, spinal cord and peripheral nerves to erectile
      function. New information regarding neuropeptides that mediate penile erection
      has extended our understanding of the central control of sex behavior, and
      melanocortin agonists may provide alternatives to existing treatment for highly
      prevalent problems including erectile dysfunction.

PMID- 15992963
TI  - Influence of cold stress on neuropeptide Y and sympathetic neurotransmission.
AB  - Chronic cold stress of rats (4 degrees C; 1-3 weeks) induced a marked increase in
      gene expression (adrenal medulla; superior cervical ganglia), tissue content
      (mesenteric arterial bed) and nerve stimulation-induced overflow of NPY
      immunoreactivity (NPYir) from the perfused mesenteric arterial bed. In contrast
      increased NPY neurotransmission was offset by an apparent decrease in the evoked
      overflow of norepinephrine (NE) due to a presumed deactivation of NE by nitric
      oxide (NO), despite increased sympathetic nerve activity. The net effect of these
      offsetting system was no change in basal or the evoked increase in perfusion
      pressure (sympathetic tone). It is concluded that differences in NPY and NE
      transmission act as an important compensatory mechanism preventing dramatic
      changes in arterial pressure when sympathetic nerve activity is high during cold
      stress.

PMID- 15992964
TI  - Activation of early components of complement targets myelin and oligodendrocytes
      in the aged rhesus monkey brain.
AB  - The disruption and loss of myelin in the white matter are some of the major
      changes that occur in the brain with age. In vitro studies suggest a role of the
      complement system in the catabolic breakdown of myelin membranes. This study
      presents findings on activation of the early components of complement cascade in
      the brains of both young and aged rhesus monkeys with evidence of increased
      complement activation in aged animals. Complement containing oligodendrocytes
      (CAOs) containing C3d and C4d complement activation products bound to
      oligodendrocytes and myelinated fibers were found in the brain of normal young
      and old animals. The CAOs, which also contained activated microglia, were
      distributed throughout the whole brain and in significantly greater numbers in
      the aged monkeys. These findings, together with the demonstration of covalent
      binding of the C3 fragments to myelin, suggest the initiation of the complement
      cascade by myelin and oligodendrocytes, which are known classical complement
      activators. Activation of terminal complement components was not demonstrable in
      the CAOs. Taken together the findings support the concept that activation of
      early components of complement in the brain may be a normal biological process
      that involves the metabolism of myelin and oligodendrocytes and up-regulates with
      age.

PMID- 15992965
TI  - Synthesis and potent antibacterial activity against MRSA of some novel 1,2
      disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidines.
AB  - A series of 28 novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5
      carboxamidine derivatives were synthesized and evaluated for in vitro
      antibacterial activities against Staphylococcus aureus and methicillin resistant
      S. aureus (MRSA) by the tube dilution method. The results showed that compounds
      45-46 and 55-57, having 3,4-dichloro substituted phenyl at the position C-2, of N
      bulky alkyl substituted benzimidazolecarboxamidines exhibited the greatest
      activity with MIC values of 1.56-0.39 microg/ml.

PMID- 15992966
TI  - Structural characterization and antimicrobial activity of 1,3-bis(2-benzimidazyl)
      2-thiapropane ligand and its Pd(II) and Zn(II) halide complexes.
AB  - 1,3-Bis(2-benzimidazyl)-2-thiapropane(L) forms 5-coordinate square pyramidal and
      4-coordinate tetrahedral, monometallic complexes with PdCl(2) and ZnX(2) (X=Cl,
      Br, I), respectively. In the palladium complex, the ligand acts as a chelating
      tridentate, through two of the nitrogen atoms in the imidazole ring and the
      sulfur atom of the bridging group together with two chloride ions forming a rare
      five coordinate complex. In the zinc halide complexes, the ligand acts as
      chelating bidentate, via two of the nitrogen atoms combined with two halide ions
      giving common tetrahedral complexes. The ligand and its complexes are
      characterized by analytical data and spectroscopic methods such as FT-Raman, FT
      IR (mid-IR, far-IR), (1)H and (13)C NMR. Their antimicrobial activities are
      evaluated by the minimal inhibitory concentration (MIC) against 10 bacteria, each
      with multiple, fresh clinical isolates (10-15), and the results are compared with
      those of ampicillin, ciprofloxacin, cefazolin, ofloxacin, and piperacillin
      antibacterial agents. The compound's antifungal activities are reported on
      Candida albicans, Candida utilis, and Cryptococcus neoformans yeasts, each with
      multiple isolates (10), and the results are referenced with amphotericin-B,
      fluconazole and flucytosine antifungal agents. In most cases, the compounds show
      broad-spectrum (Gram(+) and Gram(-)) activities that are either, more active, or
      equipotent to, the antibiotic and antifungal agents in the comparison tests.

PMID- 15992967
TI  - The molecular mechanisms involved in the cytotoxicity of alkannin derivatives.
AB  - In order to better understand the molecular aspects of the cytotoxic action
      mechanisms, the cytotoxicity of alkannin derivatives, 1-10, on five human tumor
      cell lines were examined and their standard redox potentials in aprotic medium
      were tested by means of cyclic voltammetry. It was suggested that the oxidative
      potential is closely related to the cytotoxicity. The more negative the oxidative
      potential of the hydroquinones, the higher cytotoxicity of these derivatives. The
      results of the compounds 5, 7, 9 and 10 with bad leaving groups, have higher
      cytotoxic action is not agreed with the bioreductive alkylation mechanism of
      quinones. It indicates that the molecular mechanism involving cytotoxicity of
      alkannin derivatives may favor the mechanism of production of reactive oxygen.

PMID- 15992968
TI  - One pot synthesis of oxygenated tri-heterocycles as anti-microbial agents.
AB  - A one pot synthesis of an array of angularly linked tri-heterocycles with
      coumarin, benzofuran and furan rings is described. This high yielding synthesis
      is achieved by the reaction of various 4-bromomethylcoumarins with furyl o
      hydroxyphenyl ketones involving benzylic nucleophilic displacement and
      intramolecular aldolization. All the compounds have been tested in vitro for
      their anti-microbial activity against Micrococcus aureus, Pseudomonas chinchori,
      Asperigillus fumigatus and Penicillium wortmanni at 100, 50, and 25 microg ml(-1)
      concentrations. Chloro groups in the benzofuran ring enhanced the activity.

PMID- 15992969
TI  - Cost-effectiveness of universal pneumococcal vaccination for infants in Italy.
AB  - This study aimed at estimating the health and economic outcomes of universal
      infant vaccination with seven-valent pneumococcal conjugate vaccine (PCV-7) in
      Italy. A Markov model simulated lifetime evolution of a birth cohort (538,138
      children): universal vaccination would avert 769 invasive infections, 18 deaths
      and 1323 life years. At base-case analysis, universal three-dose vaccination
      would cost euro 26,449 (95% CI: 1975-62,075) and euro 38,286 (95% CI: 22,164
      70,801) per life year-saved in the societal and the NHS perspective,
      respectively. In the hypothesis of a 5-year long protection period, vaccination
      would cost euro 32,694 and euro 43,115 per life-year saved. Considering yearly
      incidence of invasive pneumococcal disease reported for Veneto and Sardinia
      regions, PCV-7 vaccination would result highly cost-effective determining a cost
      of euro 10,479 and euro 16,890 per life year-save in the NHS and the societal
      perspective, respectively.

PMID- 15992970
TI  - Vaccination of sheep against M. paratuberculosis: immune parameters and
      protective efficacy.
AB  - Johne's disease in ruminants is caused by the pathogenic bacterium Mycobacterium
      avium subspecies paratuberculosis (Map). Currently available Map commercial
      vaccines protect against clinical disease but not infection. In this study, the
      proprietary Johne's vaccine Neoparasec and an aqueous formulation of Map 316F
      (AquaVax) were tested in sheep. Detailed immunological examination of blood and
      gut-associated lymphoid tissues was carried out on animals after vaccination and
      challenge with virulent Map to identify markers of protective immunity.
      Neoparasec vaccination provided significant protection against disease while
      AquaVax did not. Immune animals had stronger cell-mediated responses and altered
      proportions of CD4+, CD8+, CD25+ and B cells in blood, spleen and the gut
      lymphatics, than diseased animals.

PMID- 15992971
TI  - Immunodominance of low molecular weight secretory polypeptides of Mycobacterium
      tuberculosis to induce cytotoxic T-lymphocyte response.
AB  - The cytotoxic T-lymphocyte (CTL) responses to culture filtrate antigens of
      Mycobacterium tuberculosis H(37)Rv (RvCFP) and purified protein derivative (PPD)
      were investigated in active pulmonary tuberculosis patients, healthy tuberculosis
      contacts and non-contacts. Healthy tuberculin skin test (Mantoux) positive
      tuberculosis contacts demonstrated strong CTL response against RvCFP and Mantoux
      reactivity was found to correlate with CTL response. The specificity of CTL
      response in healthy Mantoux positive contacts was further assessed using
      different molecular weight fractions of RvCFP. Peripheral blood mononuclear cells
      (PBMCs) derived CTLs recognized multiple antigenic targets and demonstrated
      predominant cytotoxicity against low molecular weight (below 15 kDa) protein
      fractions as well as those migrated in the region of 30 kDa. Subsequently,
      evaluation of CTL responses against selected purified prominent T-cell antigens
      indicated maximum CTL response directed against Ag 85 complex proteins; most
      notably Ag 85 A. From this study, it is suggested that identification of more
      mycobacterial antigens activating various CTL subsets could be an important step
      for the rational designing of future antituberculous vaccine.

PMID- 15992972
TI  - Prolonged in vivo residence times of llama single-domain antibody fragments in
      pigs by binding to porcine immunoglobulins.
AB  - The therapeutic parenteral application of llama single-domain antibody fragments
      (VHHs) is hampered by their small size, resulting in a fast elimination from the
      body. Here we describe a method to increase the serum half-life of VHHs in pigs
      by fusion to another VHH binding to porcine immunoglobulin G (pIgG). We isolated
      19 pIgG-binding VHHs from an immunized llama using phage display. Six VHHs were
      genetically fused to model VHH K 609 that binds to Escherichia coli F4 fimbriae.
      All six yeast-produced genetic fusions of two VHH domains (VHH2s) were functional
      in ELISA and bound to pIgG with high affinity (1-33 nM). Four pIgG-binding VHH2s
      were administered to pigs and showed a 100-fold extended in vivo residence times
      as compared to a control VHH2 that does not bind to pIgG. This could provide the
      basis for therapeutic application of VHHs in pigs.

PMID- 15992973
TI  - Fibro-osseous pseudotumour of the digit--amputation for a benign but aggressive
      lesion.
AB  - Fibro-osseous pseudotumour is a rare, benign lesion which behaves aggressively
      and is, therefore, commonly misdiagnosed as a malignancy. Fibro-osseous
      pseudotumour shares many features with myositis ossificans and many consider it
      to be a subcutaneous variant of the latter. Early diagnosis and treatment by
      excision to normal tissue margins is important to preserve function and avoid
      digital amputation. We report a case of fibro-osseous pseudotumour of the finger
      which required ray amputation due to rapid progression of the lesion.

PMID- 15992974
TI  - Giant lipomatous tumours of the hand and forearm.
AB  - This study examines the presentation, management and outcomes of a series of 10
      patients with giant lipomatous tumours (defined as greater than 5 cm diameter) of
      the hand and forearm who presented to our orthopaedic oncology service. All
      patients underwent local staging and were discussed at our multidisciplinary
      tumour meeting prior to definitive surgery. In all cases, neurovascular
      structures required mobilization in order to excise the tumour. Seven of the
      tumours were benign lipomas and one was a neural fibrolipoma. The other two were
      well differentiated lipoma-like liposarcomas/atypical lipomatous tumours. Giant
      lipomas and well differentiated lipoma-like liposarcomas/atypical lipomatous
      tumours of the hand and forearm present infrequently and a multidisciplinary
      approach is recommended in the investigation and surgical management of these
      patients.

PMID- 15992975
TI  - Plantar feedback contributes to the regulation of leg stiffness.
AB  - BACKGROUND: Running and hopping involve moving in a bouncing fashion during which
      the limbs behave as springs. The ability to alter the stiffness of these leg
      springs is essential to maintaining an efficient gait. Since the plantar surface
      of the foot is the only part of the body to encounter the ground during bipedal
      locomotion, it would seem logical that some aspect of the neurological
      functioning of the foot is responsible for transmission of information about the
      surface characteristics to the central nervous system, resulting in changes in
      leg stiffness. METHODS: Ten subjects (9 males, 1 female) participated in this
      experiment. Lidocaine was injected inferior and posterior to the lateral
      malleolus in order to achieve tibial nerve block at the level of the ankle.
      Subjects hopped at 2.2 Hz on a force plate while data were collected at 1000 Hz.
      Data were analyzed for peak force and leg stiffness and compared using a repeated
      measures ANOVA. FINDINGS: Tactile sensation, deep pressure sensation, and
      abductor hallucis activity displayed significant decreases following the
      injection, as did postural stability. Subjects demonstrated a significantly
      decreased leg stiffness after the nerve block (P<.01). INTERPRETATION: Plantar
      sensation has an effect on regulating leg mechanics in hopping. A loss of
      sensation in this region can exert a significant impact on the properties of the
      leg in gait, and future research should determine the specific pathways by which
      plantar feedback exerts this effect.

PMID- 15992976
TI  - Specific accumulation of organochlorines in human breast milk from Indonesia:
      levels, distribution, accumulation kinetics and infant health risk.
AB  - This study determined concentrations of polychlorinated biphenyls (PCBs) and
      organochlorine compound (OC) pesticides in the milk samples of women from the
      general population in four locations of Indonesia. The most prevalent residues of
      OCs were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), whereas other OCs
      such as chlordane compounds (CHLs), tris(4-chlorophenyl)methane and
      hexachlorobenzene were lower. The levels of OCs varied between locations and
      individuals, with DDTs higher in suburban and rural areas than urban localities,
      may be due to the differences in food habits and sources between the individuals
      and locations. Data from Purwakarta site indicated continuing DDT exposure, which
      may confirm recent usage of DDT in Indonesia. A positive correlation was observed
      between concentration of OCs in human milk and age of mothers, primiparas women
      having higher OCs than multiparas, suggesting these parameters play an important
      role influencing the OC burdens in lactating women. Some individuals accumulated
      DDTs and HCHs in breast milk close to or even higher than the TDI (tolerable
      daily intake) guidelines proposed by Health Canada.

PMID- 15992977
TI  - Executive neurocognition, memory systems, and borderline personality disorder.
AB  - Borderline Personality Disorder (BPD) is a common, disabling, and burdensome
      psychiatric condition. It is characterized by turbulent fluctuations of negative
      emotions and moods, unstable and conflictual interpersonal relationships, an
      incoherent and often contradictory sense of self, and impulsive, potentially
      lethal self-injurious behaviors. The neurobehavioral facets of BPD have not been
      extensively studied. However, clinical theoreticians and researchers have
      proposed that the symptoms and behaviors of BPD are, in part, associated with
      disruptions in basic neurocognitive processes. This review summarizes and
      evaluates research that has investigated the relationship between executive
      neurocognition, memory systems, and BPD. Three historical phases of research are
      delineated and reviewed, and the methodological and conceptual challenges this
      body of investigation highlights are discussed. Laboratory-based assessment of
      executive neurocognition and memory systems is integral to an interdisciplinary
      approach to research in BPD. Such an approach holds promise in elucidating the
      neurobehavioral facets, development, diagnostic boundaries, prevention, and
      optimal interventions for this debilitating and enigmatic disorder.

PMID- 15992978
TI  - Toward a neighborhood resource-based theory of social capital for health: can
      Bourdieu and sociology help?
AB  - Within the past several years, a considerable body of research on social capital
      has emerged in public health. Although offering the potential for new insights
      into how community factors impact health and well being, this research has
      received criticism for being undertheorized and methodologically flawed. In an
      effort to address some of these limitations, this paper applies Pierre Bourdieu's
      (1986) [Bourdieu, P. (1986). Handbook of theory and research for the sociology of
      education (pp. 241-258). New York: Greenwood] social capital theory to create a
      conceptual model of neighborhood socioeconomic processes, social capital
      (resources inhered within social networks), and health. After briefly reviewing
      the social capital conceptualizations of Bourdieu and Putnam, I attempt to
      integrate these authors' theories to better understand how social capital might
      operate within neighborhoods or local areas. Next, I describe a conceptual model
      that incorporates this theoretical integration of social capital into a framework
      of neighborhood social processes as health determinants. Discussion focuses on
      the utility of this Bourdieu-based neighborhood social capital theory and model
      for examining several under-addressed issues of social capital in the
      neighborhood effects literature and generating specific, empirically testable
      hypotheses for future research.

PMID- 15992979
TI  - Social support modifies perceived stigmatization in the first years of mental
      illness: a longitudinal approach.
AB  - Perceived stigmatization of mentally ill people impairs their social relations
      and well-being. While perceived stigmatization theoretically and empirically has
      been accounted for as an independent and unalterable factor, this longitudinal
      study focuses on reciprocal effects between stigmatization and social ties. The
      duration of mental illness is included as a grouping variable to extend the
      longitudinal perspective. A sample of severely mentally ill persons (n=165) in
      two psychiatric hospitals in Zurich took part in a structured interview during
      their admission and 1 year later. Cross-lagged path models were designed to test
      the interrelations of (1) perceived stigmatization, (2) a defensive stigma coping
      orientation, (3) concrete stigmatizing experiences, and either (4) social
      network, or (5) perceived social support as dependent variables. Contrary to
      previous findings, neither of the three components of stigmatization tested has
      any influence on social network or support. Social support, though, strongly
      predicts perceived stigmatization 1 year later, but only in the group with a more
      recent onset of illness. This finding suggests that the perception of stigma is
      subject to modification in the course of new life circumstances and underlines
      the importance of activating social resources in the first years of mental
      illness. Duration of illness should be included as a central variable in future
      research, as it influences the nature of the relation between stigmatization and
      social ties.

PMID- 15992980
TI  - Patient-doctor decision-making about treatment within the consultation--a
      critical analysis of models.
AB  - This paper highlights some of the limitations of models of patient involvement in
      decision-making and explores the reasons for, and implications of, these
      limitations. Taking the three models of interpretative, shared and informed
      decision-making as examples, we focus on two limitations of the models: (1)
      neglect of which decisions the patient should be involved in (the framing
      problem) and (2) how the patient should be involved in decision-making (the
      nature of reasoning problem). Although there will inevitably be a gap between
      models and practice--this much is in the nature of the models--we suggest that
      these two issues are substantially neglected by the models and yet are
      fundamental to understanding patient-doctor decision-making. We also suggest that
      the fundamental problem that lies behind these limitations is insufficient
      attention to, and explicitness about, the dilemmas of professional ethics, which
      are played out in the professional-patient relationships that the models are
      supposed to represent, particularly with respect to the issue of expert and lay
      accountability.

PMID- 15992981
TI  - Intragenerational mobility and mortality in Oslo: social selection versus social
      causation.
AB  - We investigate the relative importance of the selection and causation hypotheses
      of social inequalities in mortality, and estimate upper and lower bounds for the
      gender-specific mobility effects. For all inhabitants of Oslo aged 50-69 years in
      1990, we knew their social class in 1960 and 1980 and whether they died between
      1990 and 1994. Analysing these data with diagonal reference models, we found
      those moving upwards in the social hierarchy to have lower mortality rates than
      their class of origin but higher mortality rates than their class of destination.
      A corresponding pattern was found for those moving downwards. Thus, social
      mobility may increase or constrict the social class mortality divide. We
      estimated the upper bound to the mobility effect to be an increase of 52% for
      males and 28% for females (situation of no causation) and the lower bound to be a
      decrease of 24% for males and 21% for females (situation of no selection).
      Because both selection and causation effects are expected to play a role and to
      work in opposite directions, the resulting effect of social mobility on the
      mortality divide may be rather small.

PMID- 15992982
TI  - Mothers on the margins: implications for eradicating perinatal HIV.
AB  - Tactics aimed at reducing perinatal transmission of HIV are proving ineffective
      at accomplishing complete eradication: a group of women with HIV remain at very
      high risk for transmitting the virus to their newborns. This study engaged a
      uniquely high-risk group of HIV-infected mothers as expert informants on
      childbearing with HIV to inform strategies to eradicate perinatal HIV
      transmission. The sample draws from an Illinois Department of Children and Family
      Services (DCFS) database of 1104 HIV-seropositive women with children in
      protective services between 1989 and 2001. Of these, 32 women knew their HIV
      positive status and gave birth to at least two children after 1997 (zidovudine
      widely implemented as standard of care). Twelve were accessible and consented to
      participate. Three others, currently pregnant, also participated. Fifteen
      interviews were completed. The 15 women had given birth to 78 children (9 HIV
      infected), fathered by 62 men. Respondents were severely socioeconomically
      marginalized. They were aware of their HIV status and the benefits of
      prophylaxis, most desired healthy babies to parent, and most delivered their
      babies in hospitals equipped to provide adequate prophylaxis. Yet most received
      inadequate or no prenatal care and did not disclose their HIV status at delivery.
      Women indicated that denial and substance use were the primary intrinsic barriers
      and disrespectful treatment was the primary extrinsic barrier to disclosure and
      care. Women's recommendations about eradication of perinatal HIV transmission
      emphasized the problem of substance use, the need for private and thorough
      communication with medical and DCFS personnel, and the need for positive social
      relationships to enable HIV positive mothers to engage in care. Attention to
      potent social and institutional barriers that impair the ability of the most
      marginalized women to disclose their HIV status and accept care is essential to
      realize eradication of perinatal transmission.

PMID- 15992983
TI  - Trustful bonds: a key to "becoming a mother" and to reciprocal breastfeeding.
      Stories of mothers of very preterm infants at a neonatal unit.
AB  - A preterm birth and subsequent hospitalization of an infant at a neonatal unit
      (NU) implies an extraordinary life situation for mothers, in which the maternal
      role and breastfeeding begin and evolve in a medical and unfamiliar setting.
      Descriptions of how women experience "becoming a mother" and breastfeeding in
      such a situation are sparse and this question was addressed in the present study.
      In this qualitative study, inspired by the grounded theory approach, in-depth
      interviews were conducted with 25 mothers whose very preterm infants had been
      cared for in seven NUs in Sweden. Findings indicated the importance of quality in
      social bonds with the infant, father, staff and other mothers at the NU, for
      "becoming mothers" and experiencing mutually satisfying breastfeeding. Three
      themes comprised a structure for descriptions of experiences, social bonds and
      mediated emotions: (1) 'loss' of the infant and the emotional chaos--"putting
      life on hold"; (2) separation--a sign of being unimportant as a person and
      mother; and (3) critical aspects of becoming more than a physical mother. The
      qualities were described as trustful or distrustful, characterized by
      accompanying feelings of pride/trust or shame/distrust. Social bonds were
      affected not only by the interpersonal interplay but also by the public
      environment and care routines. In conclusion, the contextual setting and
      distrustful social bonds impaired the ability to "become mothers" and the
      sensation of reciprocity i.e. breastfeeding becoming dutiful and not mutually
      satisfying. As breastfeeding is an intimate interplay and a personal choice it
      was considered that the best breastfeeding support would seem to be provision of
      a favorable environment that enhances the mother's confidence in herself. The
      contextual setting should be modeled such as to create conditions for a trustful
      and reciprocal mother-infant bond.

PMID- 15992984
TI  - Narrativizing errors of care: critical incident reporting in clinical practice.
AB  - This paper considers the rise across acute care settings in the industrialized
      world of techniques that encourage clinicians to record their experiences about
      adverse events they are personally involved in; that is, to share narratives
      about errors, mishaps or 'critical incidents'. The paper proposes that critical
      incident reporting and the 'root cause' investigations it affords, are both
      central to the effort to involve clinicians in managing and organizing their
      work, and a departure from established methods and approaches to achieve
      clinicians' involvement in these non-clinical domains of health care. We argue
      that critical incident narratives render visible details of the clinical work
      that have thus far only been discussed in closed, paperless meetings, and that,
      as narratives, they incite individuals to share personal experiences with parties
      previously excluded from knowledge about failure. Drawing on a study of 124
      medical retrieval incident reports, the paper provides illustrations and
      interpretations of both the narrative and the meta-discursive dimensions of
      critical incident reporting. We suggest that, as a new and complex genre,
      critical incident reporting achieves three important objectives. First, it
      provides clinicians with a channel for dealing with incidents in a way that
      brings problems to light in a non-blaming way and that might therefore be morally
      satisfying and perhaps even therapeutic. Second, these narrations make available
      new spaces for the apprehension, identification and performance of self. Here,
      the incident report becomes a space where clinicians publicly perform concern
      about what happened. Third, incident reporting becomes the basis for radically
      altering the clinician-organization relationship. As a complex expression of
      clinical failure and its re-articulation into organizational meta-discourse,
      incident reporting puts doctors' selves and feelings at risk not just within the
      relative safety of personal or intra-professional relationships, but also in the
      normative context of organizational coordination, accountability, planning and
      management.

PMID- 15992985
TI  - The role of proximal-enhancer elements in the glucocorticoid regulation of
      carbamoylphosphate synthetase gene transcription from the upstream response unit.
AB  - As part of the urea cycle, carbamoylphosphate synthetase (CPS) converts toxic
      ammonia resulting from amino-acid catabolism into urea. Liver-specific and
      glucocorticoid-dependent expression of the gene involves a distal enhancer, a
      promoter-proximal enhancer, and the minimal promoter itself. When challenged with
      glucocorticoids, the glucocorticoid-responsive unit (GRU) in the distal enhancer
      of the carbamoylphosphate-synthetase gene can only activate gene expression if,
      in addition to the minimal promoter, the proximal enhancer is present. Here, we
      identify and characterise two elements in the proximal CPS enhancer that are
      involved in glucocorticoid-dependent gene activation mediated by the GRU. A
      purine-rich stretch forming a so-called GAGA-box and a glucocorticoid-response
      element (GRE) are both crucial for the efficacy of the GRU and appear to
      constitute a promoter-proximal response unit that activates the promoter. The
      glucocorticoid response of the CPS gene is, therefore, dependent on the combined
      action of a distal and a promoter-proximal response unit.

PMID- 15992986
TI  - Out-of-hospital cardiac arrest rectilinear biphasic to monophasic damped sine
      defibrillation waveforms with advanced life support intervention trial (ORBIT).
AB  - BACKGROUND: Although biphasic defibrillation waveforms appear to be superior to
      monophasic waveforms in terminating VF, their relative benefits in out-of
      hospital resuscitation are incompletely understood. Prior comparisons of
      defibrillation waveform efficacy in out-of-hospital cardiac arrest (OHCA) are
      confined to patients presenting in a shockable rhythm and resuscitated by first
      responder (basic life support). This effectiveness study compared monophasic and
      biphasic defibrillation waveform for conversion of ventricular arrhythmias in all
      OHCA treated with advance life support (ALS). METHODS AND RESULTS: This
      prospective randomized controlled trial compared the rectilinear biphasic (RLB)
      waveform with the monophasic damped sine (MDS) waveform, using step-up energy
      levels. The study enrolled OHCA patients requiring at least one shock delivered
      by ALS providers, regardless of initial presenting rhythm. Shock success was
      defined as conversion at 5s to organized rhythm after one to three escalating
      shocks. We report efficacy results for the cohort of patients treated by ALS
      paramedics who presented with an initially shockable rhythm who had not received
      a shock from a first responder (MDS: n=83; RLB: n=86). Shock success within the
      first three ascending energy shocks for RLB (120, 150, 200J) was superior to MDS
      (200, 300, 360J) for patients initially presenting in a shockable rhythm (52%
      versus 34%, p=0.01). First shock conversion was 23% and12%, for RLB and MDS,
      respectively (p=0.07). There were no significant differences in return of
      spontaneous circulation (47% versus 47%), survival to 24h (31% versus 27%), and
      survival to discharge (9% versus 7%). Mean 24h survival rates of bystander
      witnessed events showed differences between waveforms in the early circulatory
      phase at 4-10 min post event (mean (S.D.) RLB 0.45 (0.07) versus MDS 0.31 (0.06),
      p=0.0002) and demonstrated decline as time to first shock increased to 20 min.
      CONCLUSION: Shock success to an organized rhythm comparing step-up protocol for
      energy settings demonstrated the RLB waveform was superior to MDS in ALS
      treatment of OHCA. Survival rates for both waveforms are consistent with current
      theories on the circulatory and metabolic phases of out-of-hospital cardiac
      arrest.

PMID- 15992987
TI  - Use of an automatic mechanical chest compression device (LUCAS) as a bridge to
      establishing cardiopulmonary bypass for a patient with hypothermic cardiac
      arrest.
AB  - We report the case of a victim of deep accidental hypothermia who was extracted
      from the ice and received 1.5 h of mechanical chest compression. This was
      followed with rapid rewarming on cardiopulmonary bypass and resulted in good
      physical and mental recovery. This management option should be considered for
      similar victims.

PMID- 15992988
TI  - Adsorption of single chain zwitterionic phosphocholine surfactants: effects of
      length of alkyl chain and head group linker.
AB  - The adsorption of a range of single chain zwitterionic phosphocholine surfactants
      (C(n)P(m)C) at the air/liquid interface has been studied by a combination of
      surface tension and neutron reflectivity. The critical micellar concentration
      (CMC) for C(n)PC (or C(n)P(2)C), where n varied from 12, 14 to 16, was found to
      be 0.91, 0.14, and 1.2 x 10(-2) mM respectively, and followed the same trend as
      observed for other zwitterionic and non-ionic surfactants. The area per molecule
      at the CMC, A(cmc), for C(n)PC was found to remain constant between 50 and 53
      A(2), indicating that the increase in the alkyl chain length had little effect on
      A(cmc) at the interface. The neutron reflection measurement also showed an almost
      constant layer thickness (tau) of 20+/-2 A from all the alkyl chain deuterated PC
      surfactants (dC(n)hPC) in null reflecting water (NRW), suggesting that the alkyl
      chains of the surfactant responded to changes in either chain length or solution
      concentration by varying their angle of tilt. In contrast, increasing the length
      of head group linker between P and N atoms in C(12)P(m)C, where m=2, 4, to 6,
      resulted in a much slower decrease of CMC from 0.91, 0.7, to 0.5 mM, consistent
      with a different contribution to the free energy of micellization. A(cmc) for
      C(12)P(m)C did not vary when m was increased from 2 to 4, and this observation
      together with the thickness of the head group region indicated an almost
      perpendicular projection of the head group in C(12)P(2)C and C(12)P(4)C. A
      further increase in m to 6 resulted in an A(cmc) of 70 A(2). This increase in
      A(cmc) however did not result in any change in either the total layer thickness
      or the fraction of the head group region submerged in the aqueous subphase,
      suggesting that the head group in C(12)P(6)C was bent away from the surface
      normal direction. Both increase in temperature from 25 to 40 degrees C and the
      addition of 0.1 M NaCl had little effect on the area per molecule or the
      thickness of C(12)P(m)C surfactant layer, showing that the C(12)P(m)C series
      behaved like C(n)P(2)C series. The main conclusion from this study is that for
      all the C(n)P(m)C surfactants studied, change in m or n has little effect on the
      total thickness, the thickness of the alkyl chain or that of the head group
      region.

PMID- 15992989
TI  - International trade and air pollution: estimating the economic costs of air
      emissions from waterborne commerce vessels in the United States.
AB  - Although there is a burgeoning literature on the effects of international trade
      on the environment, relatively little work has been done on where trade most
      directly effects the environment: the transportation sector. This article shows
      how international trade is affecting air pollution emissions in the United
      States' shipping sector. Recent work has shown that cargo ships have been long
      overlooked regarding their contribution to air pollution. Indeed, ship emissions
      have recently been deemed "the last unregulated source of traditional air
      pollutants". Air pollution from ships has a number of significant local,
      national, and global environmental effects. Building on past studies, we examine
      the economic costs of this increasing and unregulated form of environmental
      damage. We find that total emissions from ships are largely increasing due to the
      increase in foreign commerce (or international trade). The economic costs of SO2
      pollution range from dollars 697 million to dollars 3.9 billion during the period
      examined, or dollars 77 to dollars 435 million on an annual basis. The bulk of
      the cost is from foreign commerce, where the annual costs average to dollars 42
      to dollars 241 million. For NOx emissions the costs are dollars 3.7 billion over
      the entire period or dollars 412 million per year. Because foreign trade is
      driving the growth in US shipping, we also estimate the effect of the Uruguay
      Round on emissions. Separating out the effects of global trade agreements reveals
      that the trade agreement-led emissions amounted to dollars 96 to dollars 542
      million for SO2 between 1993 and 2001, or dollars 10 to dollars 60 million per
      year. For NOx they were dollars 745 million for the whole period or dollars 82
      million per year. Without adequate policy responses, we predict that these trends
      and costs will continue into the future.

PMID- 15992990
TI  - Transient receptor potential vanilloid type 1 (TRPV1) expression changes from
      normal urothelium to transitional cell carcinoma of human bladder.
AB  - OBJECTIVE: To investigate possible changes in the expression of the transient
      receptor potential vanilloid type 1 (TRPV1) from normal urothelium to
      transitional cell carcinoma (TCC) of human bladder. METHODS: Specimens from
      normal bladder (n=13, mean age 62 yrs), superficial TCC (n=16, mean age 62,4 yrs)
      and muscle invasive bladder cancer (n=12, mean age 67 yrs), were obtained by
      multiple cold cup and full-thickness biopsy during open surgery. All the
      specimens were processed for H&E staining, immunohistochemistry and Western Blot
      analysis. RESULTS: In controls, the urothelium showed a labelling whose intensity
      was higher in the superficial cells than in the basal and club-shaped ones. In
      the superficial TCC, the urothelium showed a reduced labelling intensity. In the
      muscle invasive TCC, a very light labelling was occasionally detected in
      scattered superficial cells and no labelling was present in the basal cells and
      in those that had invaded the muscle. In controls, Western Blot analysis
      recognized two thick, intensely stained bands, with a molecular weight of
      approximately 100 and 95 kDa. In all superficial TCC there were two bands similar
      to control ones and in the muscle invasive two very thin, lightly stained bands.
      No band was detected in the patients staged as pT4. CONCLUSION: These data
      demonstrated a progressive loss of TRPV1 expression in the urothelium as TCC
      stage increased and cell differentiation was lower. Future studies will establish
      the importance of this loss for TCC differentiation and progression.

PMID- 15992991
TI  - Skewing towards neuroendocrine phenotype in high grade or high stage androgen
      responsive primary prostate cancer.
AB  - OBJECTIVE: The prognostic influence of neuroendocrine (NE) differentiation in
      prostate cancer patients is not yet properly established. In a series of primary
      hormone-naive prostate cancers from a patient population that underwent radical
      prostatectomy, we wanted to determine the relationship between NE phenotype
      expression and Gleason sum, disease stage, and serum PSA concentration. METHODS:
      Chromogranin A (CgA) expression was scored and compared in 105 consecutive
      primary prostate cancers with their homologous preoperative tumor prostate
      biopsies. RESULTS: High grade or high stage prostate cancers expressed a
      significantly higher CgA score than low grade or localized diseases (p < 0.005).
      Both the CgA score of the surgical specimens and the PSA level in the serum
      increased linearly (p = 0.001). In the samples of many corresponding tumor
      biopsies no significant CgA staining was found. CONCLUSION: NE differentiation in
      primary untreated prostate cancer is closely associated with the major prognostic
      parameters of survival. This association cannot be shown by evaluating the CgA
      staining in tumor biopsies.

PMID- 15992992
TI  - Correlation of magnetic resonance images with neuropathology in acute Wernicke's
      encephalopathy.
AB  - We correlated serial brain MRIs with neuropathological findings in a 16-year-old
      female whose autopsy was consistent with Wernicke's encephalopathy (WE).
      Diffusion-weighted imaging, diffusion coefficients mapping and neuropathology
      findings were suggested vasogenic edema in the periaqueductal and peri-the-fourth
      ventricular areas. This is the first documented case report to make this direct
      comparison. The characteristic WE changes in the mammillary body was also
      correlated with the findings of MRI with contrast enhancement. Bilateral cortical
      lesions revealed by MRI were atypical and rare in WE and were not evidenced by
      pathological changes.

PMID- 15992993
TI  - Polymorphism of glutathione S-transferase omega gene and risk of cancer.
AB  - Polymorphic glutathione S-transferase (GST) genes causing variations in enzyme
      activity may influence individual susceptibility to cancer. Though polymorphisms
      have been reported in GSTO1 and GSTO2, their predisposition to cancer risk has
      not yet been explored. In this case control study, 28 cases of hepatocellular
      carcinoma, 30 cases of cholangiocarcinoma, 31 cases of colorectal cancer, 30
      cases of breast cancer and 98 controls were compared for frequencies of GSTO1 and
      GSTO2 genotypes. The statistical analysis provided the support for the difference
      in genotypic distribution for GSTO1*A140D between hepatocellular carcinoma (OR
      23.83, CI 95%: 5.07-127), cholangiocarcinoma (OR 8.5, CI 95%: 2.07-37.85), breast
      cancer (OR 3.71, CI 95%: 1.09-13.02) and control. With regards to GSTO2*N140D
      polymorphism, there was no difference in genotypic distribution between all the
      types of cancer and control. The study suggests that GSTO1*A140D polymorphism
      could play an important role as a risk factor for the development of
      hepatocellular carcinoma, cholangiocarcinoma and breast cancer.

PMID- 15992994
TI  - Humoral immune responses of lung cancer patients against tumor antigen NY-ESO-1.
AB  - The cancer-associated antigen NY-ESO-1 is expressed in a number of malignancies
      of different histological type. Patients with NY-ESO-1 expressing tumors have
      been shown to bear circulating autoantibodies against this antigen. In this
      study, we have assessed the NY-ESO-I autoantibody response in patients with lung
      cancer by a serum ELISA. Using a serum dilution of 1:400 we detected
      seroreactivity in 35 of 175 (20%) of patients. Incidence of autoantibodies was
      significantly higher in patients suffering from non small cell lung cancer
      (NSCLC, 23%) as compared to those with small cell lung cancer (SCLC, 9%). In the
      NSCLC group, NY-ESO-I antibody was significantly more frequent in patients with
      undifferentiated tumors (40%) as compared to patients with either adenocarcinoma
      or squamous cell carcinoma (15 and 29%). Our observations indicate that induction
      of NY-ESO-I autoantibodies depends on the histological subtype within a given
      tumor entity.

PMID- 15992995
TI  - Double stimulation of tiny skin areas in human subjects increases the number of C
      and Adelta-fiber responses.
AB  - The stimulation of tiny skin areas has been shown to be a useful method for the
      investigation of the central nervous processing of C-fiber stimulation. However,
      recent studies have also indicated that most subjects fail to recognize a large
      number of such stimulation. This fact renders this method to be rather time
      consuming, a fact that limits its applicability. To reduce the duration of
      examination, we here examined the effects of double stimulation of tiny skin
      areas as compared to the stimulation of tiny skin areas with a single stimulus.
      The comparison is based on subjects' number of recognized stimuli for single and
      double stimulation and ratings of stimulus intensity. Double stimulation of tiny
      skin areas resulted in a significant increase of the number of recognized stimuli
      as compared to single stimulation. This increase of the number of recognized
      stimuli is accompanied by an increase of the averaged subjects' experience of
      stimulus intensity. However, there was no significant increase of intensity
      rating for the different types of fibers stimulated. Data indicate that the
      double stimulation of tiny skin areas represents an alternative option to the
      application of single stimuli to tiny skin areas that significantly reduces the
      exposure time of subjects in order to evaluate behavioral consequences of the
      stimulation as well as central nervous processing of C- and Adelta-fiber input.

PMID- 15992996
TI  - Detection of thromboxane A(2) receptor mRNA in rabbit nodose ganglion neurons.
AB  - Thromboxane A(2) (TXA(2)) is an arachidonic acid metabolite that is released
      during tissue trauma and elicits platelet aggregation and vascular smooth muscle
      contraction. Previous research has shown that TXA(2) stimulates pulmonary and
      cardiac vagal afferent neurons. Therefore, we hypothesized that the presence of
      the TXA(2) receptor (TP) in vagal neurons would allow for stimulation or
      modulation of these neurons by TXA(2). To test this hypothesis, single cell RT
      PCR was employed using neurons obtained from primary cell cultures of nodose
      ganglia excised from adult rabbits. Since the sequence for the rabbit TP gene was
      unknown, a portion of the rabbit TP cDNA was first amplified, cloned, and
      sequenced. Primer sets for TP were then designed based on this sequence and used
      in conjunction with a neuronal marker, medium weight neurofilament (NFM), in
      multiplex RT-PCR reactions. Ninety-three cells were isolated from culture and RT
      PCR was carried out on individual cells. Using an aliquot from the initial RT-PCR
      reaction, a second round of PCR was then employed in which the NFM and TP primer
      sets were split up into separate reactions. Twenty-three of the 82 cells that
      were positive for NFM were also positive for TP. Therefore, we conclude that the
      presence of TP mRNA in a subset of cultured nodose ganglion neurons allows for
      the possibility that TXA(2) may directly stimulate or modulate vagal afferent
      neurons.

PMID- 15992997
TI  - Anti-Trichinella antibodies detected in chronically infected horses by IFA and
      Western blot, but not by ELISA.
AB  - In the Balkan countries, where trichinellosis is a re-emerging zoonosis, it is of
      great importance to determine Trichinella infection prevalence among the major
      hosts, including horses. One method for monitoring prevalence is serological
      surveillance; however, the validity of serological methods in horses is not well
      understood. The dynamics of anti-Trichinella IgG production and circulating
      excretory/secretory (ES) antigens were investigated in three horses
      experimentally-infected with Trichinella spiralis. Horses were slaughtered at 32
      week post infection (p.i.). Low worm burdens were found in all three animals.
      Anti-Trichinella IgG was detected up to 32 weeks p.i. by an indirect
      immunofluorescence assay (IFA) and by Western blot (Wb), but not by ELISA. The
      ELISA test detected antibodies for only a short period of time (up to 18 weeks
      p.i. using ES antigen or up to 20 weeks p.i. using tyvelose-BSA antigen). The
      presence of circulating muscle larvae ES antigen in sera of infected horses was
      observed by dot blot from the 4th week p.i. up to the 32nd week p.i.

PMID- 15992998
TI  - Simple species identification of Trichinella isolates by amplification and
      sequencing of the 5S ribosomal DNA intergenic spacer region.
AB  - We developed a PCR-based assay using a single primer pair to amplify the 5S
      ribosomal DNA intergenic spacer region to identify Trichinella isolates. In our
      method, amplified products are directly sequenced on both strands and compared to
      GenBank sequences. Using this method, we were able to identify Trichinella
      spiralis, T. britovi and T. nativa. This method permits rapid species
      identification of Trichinella isolates; however, further evaluation is required
      before recommending this approach for routine use.

PMID- 15992999
TI  - Profiling excretory/secretory proteins of Trichinella spiralis muscle larvae by
      two-dimensional gel electrophoresis and mass spectrometry.
AB  - Infection of mammalian skeletal muscle with the intracellular parasite
      Trichinella spiralis results in profound alterations in the host cell and a
      realignment of host cell gene expression. The role of parasite
      excretory/secretory (E/S) products in mediating these effects is unknown, largely
      due to the difficulty in identifying and assigning function to individual
      proteins. In this study, we have used two-dimensional electrophoresis to analyse
      the profile of muscle larva excreted/secreted proteins and have coupled this to
      protein identification using MALDI-TOF mass spectrometry. Interpretation of the
      peptide mass fingerprint data has relied primarily on the interrogation of a
      custom-made Trichinella EST database and the NemaGene cluster database for T.
      spiralis. Our results suggest that this proteomic approach is a useful tool to
      study protein expression in Trichinella spp. and will contribute to the
      identification of excreted/secreted proteins.

PMID- 15993000
TI  - Trichinae certification in the United States pork industry.
AB  - Control of Trichinella infection in U.S. pork has traditionally been accomplished
      by inspection of individual carcasses at slaughter or by post-slaughter
      processing to inactivate parasites. We propose that an alternative to individual
      carcass testing or processing can be used when pigs are raised in production
      systems where risk of exposure to Trichinella spiralis has been mitigated.
      Declines in prevalence of this parasite in U.S. domestic swine during the last 30
      years, coupled with improvements in pork production systems, now allow
      Trichinella control to be shifted to the farm through implementation of specific
      pork production practices. Knowledge of risk factors for exposure of swine to T.
      spiralis was used to develop an objective audit of risk that can be applied to
      pork production sites. In a pilot study, 461 production site audits were
      performed by trained veterinary practitioners. The on-farm audit included aspects
      of farm management, bio-security, feed and feed storage, rodent control programs
      and general hygiene. Of the 461 production site audits, 450 audits (97.6%)
      indicated compliance with the required good production practices. These sites are
      eligible for certification under the U.S. Trichinae Certification Program and
      will be audited regularly to maintain that status. The described trichinae
      certification mechanism will establish a process for ensuring the Trichinella
      safety of swine, and ultimately food products derived from swine, at the
      production level.

PMID- 15993001
TI  - Feeding predilection of Gulf Coast tick, Amblyomma maculatum Koch, nymphs on
      cattle.
AB  - Gulf Coast tick nymphs successfully attached and fed on cattle after being freely
      released. Six Hereford heifers were each infested with approximately 2000 Gulf
      Coast tick nymphs, three with a strain originating from Refugio Co., TX, and
      three with ticks from Osage Co., KS by free release on the head and legs to
      simulate field acquisition of questing nymphs. Two re-infestations were
      conducted, the first at 7 days and the second at 28 days. Nymph dispersal was
      estimated by daily inspection of 22 body areas and removal of engorging ticks
      from the third to the fifth days post-infestation. Total recovery of engorging
      Texas nymphs was 3.0, 10.2, and 0% and Kansas nymphs was 21.5, 3.3, and 0% for
      infestations one, two and three, respectively. Immunological resistance to tick
      infestation expressed as cellular hypersensitivity was evident against Kansas
      nymphs in the second infestation and against both tick strains in the third
      infestation. Ticks removed from the withers, midline, and tail-head areas
      accounted for 68% of the total nymphs recovered in the first two infestations.
      Within these areas, nymphs were observed to aggregate in small spots where the
      hair was less dense or naturally parted and the remainder were found scattered in
      dense hair.

PMID- 15993002
TI  - Skin substitute jacket for burns to the trunk.

PMID- 15993003
TI  - Spatio-temporal cholinergic modulation in cultured networks of rat cortical
      neurons: spontaneous activity.
AB  - Activation of the cholinergic innervation of the cortex has been implicated in
      sensory processing, learning, and memory. At the cellular level, acetylcholine
      both increases excitability and depresses synaptic transmission, and its effects
      on network firing are hard to predict. We studied the effects of carbachol, a
      cholinergic agonist, on network firing in cultures of rat cortical neurons, using
      electrode arrays to monitor the activity of large numbers of neurons
      simultaneously. These cultures show stable spontaneous synchronized burst firing
      which propagates through dense synaptic connections. Carbachol (10-50 microM),
      acting through muscarinic receptors, was found to induce a switch to asynchronous
      single-spike firing and to result in a loss of regularity and fragmentation of
      the burst structure. To obtain a quantitative measure of cholinergic actions on
      cortical networks, we applied a cluster Poisson-process model to sets of
      paralleled spike-trains in the presence and absence of carbachol. This revealed
      that the time series can be well-characterized by such a simple model, consistent
      with the observed 1/f(b)-like spectra (0.04<b<2.08). After applying higher
      concentrations of carbachol the property of the spectra shifted toward a Poisson
      process (white) spectrum. These results indicate that cholinergic
      neurotransmitters have a strong and reliable desynchronizing action on cortical
      neural activity.

PMID- 15993004
TI  - A comparison of the psychometric properties of the hooked on nicotine checklist
      and the modified Fagerstrom tolerance questionnaire.
AB  - We compared the psychometric properties of the Hooked on Nicotine Checklist
      (HONC) and the Modified Fagerstrom Tolerance Questionnaire (MFTQ). Adolescent
      current smokers (n = 215) completed both instruments three times, at baseline and
      6- and 12-month follow-up. Internal consistency of the HONC was high (alpha =
      0.92), as was its stability over the follow-up interval (intraclass correlation
      (ICC) = 0.93 over 6 months and 0.91 over 1 year). Internal consistency of the
      MFTQ was acceptable (alpha = 0.83), and its stability over the follow-up interval
      was similar to that reported previously (ICC = 0.79 at 6 months and 0.76 at 1
      year). The HONC predicted smoking at both follow-up points, while the MFTQ did so
      only at 6 months. The HONC compared favorably with the MFTQ in all respects. The
      most important advantage of the HONC is that it is measuring a clearly defined
      concept, diminished autonomy over tobacco, which begins when the sequelae of
      tobacco use present a barrier to quitting.

PMID- 15993005
TI  - Nine-year prediction of adolescent smoking by number of smoking parents.
AB  - For scientific and public health reasons, it is important to identify the role of
      family influences on child smoking acquisition. Using a well-followed (>90%)
      cohort of 3,012 children and their parents, this study prospectively investigated
      the influence of smoking by 0 vs. 1 vs. 2 parents when the children were young
      (3rd grade), on whether the children subsequently became daily smokers. It is the
      only study to investigate the prediction of child/adolescent smoking at the end
      of the smoking acquisition period (12th grade) by parental smoking at the start
      of the period (3rd grade). Logistic regression analyses revealed that having one
      parent who smokes substantially increases the risk that children will become
      daily smokers, relative to families where neither parent smokes (OR=1.90, p<.01).
      There is no evidence that the increased risk depends on parent or child gender.
      These results suggest the need for public health interventions that inform
      parents of young children that their own smoking behavior increases their
      children's risk for future smoking.

PMID- 15993006
TI  - Negative Mood Regulation (NMR) expectancies, mood, and affect intensity among
      clients in substance disorder treatment facilities.
AB  - Negative mood regulation (NMR) expectancies, stress, anxiety, depression and
      affect intensity were examined by means of self-report questionnaires in 158
      volunteers, including 99 clients enrolled in addiction treatment programs. As
      expected, addicts reported significantly higher levels of stress, anxiety,
      depression and affect intensity and lower levels of NMR compared to non-addict
      controls. NMR was negatively correlated with stress, anxiety, depression and
      affect intensity. The findings indicate that mood self-regulation is impaired in
      addicts. Low NMR and high affect intensity may predispose to substance abuse and
      addiction, or alternatively may reflect chronic drug-induced affective
      dysregulation.

PMID- 15993007
TI  - Insoluble fibrin may reduce turbulence and bind blood components into clots.

PMID- 15993008
TI  - Suppressive effects of dichloromethane fraction from the Areca catechu nut on
      naloxone-precipitated morphine withdrawal in mice.
AB  - In the present study, we investigated the effect of the dichloromethane fraction
      from Areca catechu nut on the severity of naloxone-precipitated morphine
      withdrawal in morphine-dependent mice. A single intraperitoneal injection of
      dichloromethane fraction at dose of 125 and 175 mg/kg significantly delayed the
      onset of withdrawal jumping behavior in a concentration-dependent manner compared
      to that of saline controls. The dichloromethane fractions also significantly
      decreased jumping numbers and faecal and urinary excretions during the withdrawal
      period.

PMID- 15993009
TI  - OxyR mediated compensatory expression between ahpC and katA and the significance
      of ahpC in protection from hydrogen peroxide in Xanthomonas campestris.
AB  - katA and ahpC, encoding monofunctional catalase and alkyl hydroperoxide
      reductase, respectively, play important protective roles against peroxide
      toxicity in Xanthomonas campestris pv. phaseoli (Xp). The expression of both katA
      and ahpC is controlled by the global peroxide sensor and transcriptional
      activator, OxyR. In Xp, these two genes have compensatory expression patterns.
      Inactivation of katA leads to an increase in the level of AhpC and a concomitant
      increase in resistance to tert-butyl hydroperoxide (tBOOH). High-level expression
      of katA from an expression vector in Xp also lowered the level of ahpC
      expression. The compensatory regulation of katA and ahpC was mediated by OxyR,
      since the compensatory response was not observed in an oxyR mutant background.
      ahpC and katA play important but unequal roles in protecting Xp from H(2)O(2)
      toxicity. These observations, taken together with a previous observation that an
      ahpC mutant expresses high levels of KatA and is hyper-resistant to H(2)O(2),
      suggest the possibility that inactivation of either gene leads to accumulation of
      intracellular H(2)O(2). This in turn oxidizes reduced OxyR and converts the
      regulator to the oxidized form that then activates expression of genes in the
      OxyR regulon.

PMID- 15993010
TI  - Fluorescence based measurements of Fusobacterium nucleatum coaggregation and of
      fusobacterial attachment to mammalian cells.
AB  - Fusobacterium nucleatum is a common oral anaerobe associated with gingivitis,
      periodontal disease and preterm deliveries. Coaggregation among oral bacteria is
      considered to be a significant factor in dental plaque development. Adhesion to
      host cells was suggested to be important for the F. nucleatum virulence
      associated with oral inflammation and with preterm births. An uncharacterized
      fusobacterial galactose inhibitible adhesin mediates coaggregation of F.
      nucleatum 12230 and F. nucleatum PK1594 with the periodontal pathogen
      Porphyromonas gingivalis. This adhesin is also involved with the attachment of
      both fusobacterial strains to host cells. However, it has been suggested that
      additional unidentified fusobacterial adhesins are involved in F. nucleatum
      virulence associated with preterm births. In this study, a fluorescence-based
      high throughput sensitive and reproducible method was developed for measuring
      bacterial coaggregation and bacterial attachment to mammalian cells. Using this
      method we found that coaggregation of F. nucleatum 4H with P. gingivalis and its
      attachment to murine macrophages is less inhibitible by galactose than that of F.
      nucleatum PK1594. These findings suggest that F. nucleatum 4H can serve as a
      model organism for identifying nongalactose inhibitible F. nucleatum adhesins
      considered to be involved in fusobacterial attachment to mammalian cells.

PMID- 15993011
TI  - Environmental chemical tributyltin augments adipocyte differentiation.
AB  - Scientific attention has been drawn to environmental factors that affect obesity
      and type II diabetes. Previously, acute organotin toxicosis was reported to
      induce hyperglycemia without morphological abnormalities in islet tissue,
      suggesting that these compounds have a direct effect on adipose tissue.
      Therefore, we investigated the effect of tributyltin (TBT) on adipocyte
      differentiation. When confluent 3T3-L1 cells were incubated with TBT for 2 days
      in the presence or absence of isobutyl methylxanthine, dexamethasone and insulin
      (MDI), the lipid accumulation in adipocytes was greatly enhanced. These
      morphological changes induced by TBT were accompanied by the expression of a
      differentiation marker for adipocytes in a dose-dependent manner. Co-treatment
      with the peroxisome proliferator-activated receptor (PPAR)gamma antagonist GW9662
      did not inhibit the effect of TBT, suggesting that the observed effect of TBT may
      not be PPARgamma-dependent. Although TBT was reported to exert androgenic effects
      and inhibit the activity of aromatase, treatments with dihydrotestosterone or
      17beta-estradiol did not influence the aP2 expression in 3T3-L1 cells, suggesting
      that the TBT effect does not occur via sex-steroids. These findings indicate that
      TBT may be one of the environmental chemicals that lead to excessive accumulation
      of adipose tissue, which can result in obesity.

PMID- 15993012
TI  - Pituitary gonadotropin-releasing hormone (GnRH) receptor: structure, distribution
      and regulation of expression.
AB  - Reproduction in mammals is controlled by interactions between the hypothalamus,
      anterior pituitary and gonads. Interaction of GnRH with its cognate receptor is
      essential to regulating reproduction. Characterization of the structure,
      distribution and expression of GnRH receptors (GnRH-R) has furthered our
      understanding of the physiological consequences of GnRH stimulation of pituitary
      gonadotropes. Based on the putative topology of the amino acid sequence of the
      GnRH-R and point mutation studies, key elements of the GnRH-R have been
      identified to play a role in ligand recognition and binding, G-protein activation
      and internalization. Normally, reproductive function is mediated by GnRH-R
      expressed only on the membranes of pituitary gonadotropes. The density of GnRH-R
      on gonadotropes determines their ability to respond to GnRH. This density is
      highest just prior to ovulation and likely is important for complete expression
      of the pre-ovulatory surge of LH. Therefore, knowledge regarding what regulates
      the density of GnRH-R is essential to understanding changes in pituitary
      sensitivity to GnRH and ultimately, to expression of the LH surge. Regulation of
      GnRH-R gene expression is influenced by a multitude of factors including gonadal
      steroid hormones, inhibin, activin and perhaps most importantly GnRH itself.

PMID- 15993013
TI  - Synthesis and secretion of GnRH.
AB  - Comprehensive studies have provided a clear understanding of the effects of
      gonadal steroids on the secretion of gonadotropin releasing hormone (GnRH), but
      some inconsistent results exist with regard to effects on synthesis. It is clear
      that regulation of both synthesis and the secretion of GnRH are effected by
      neurotransmitter systems in the brain. Thus, steroid regulation of GnRH synthesis
      and secretion can be direct, but the predominant effects are transmitted through
      steroid-responsive neuronal systems in various parts of the brain. There is also
      emerging evidence of direct effects on GnRH cells. Overriding effects on
      synthesis and secretion of GnRH can be observed during aging, in undernutrition
      and under stressful situations; these involve various neuronal systems, which may
      have serial or parallel effects on GnRH cells. The effect of aging is accompanied
      by changes in GnRH synthesis, but comprehensive studies of synthesis during
      undernutrition and stress are less well documented. Altered GnRH and gonadotropin
      secretion that occurs in seasonal breeding animals and during the pubertal
      transition is not generally accompanied by changes in GnRH synthesis. Secretion
      of GnRH from the brain is a reflection of the inherent function of GnRH cells and
      the inputs that integrate all of the central regulatory elements. Ultimately, the
      pattern of secretion dictates the reproductive status of the organism. In order
      to fully understand the central mechanisms that control reproduction, more
      extensive studies are required on the neuronal circuitry that provides input to
      GnRH cells.

PMID- 15993014
TI  - Lateralization of the effects of the benzodiazepine drug oxazepam on medial
      olivocochlear system activity in humans.
AB  - Benzodiazepines (Bzd) are known to interact with GABAergic inhibitory
      neurotransmission. Previous research on their effect on human auditory efferent
      pathways--through evoked otoacoustic emissions suppression by contralateral
      acoustic stimulation (CAS)--indicated a decrease in medial olivocochlear (MOC)
      efferent system inhibitory activity, after oral intake of oxazepam-
      representative of the Bzd drug class. To date, this pharmacological effect was
      only assessed in the right ear. Since a leftward asymmetry of Bzd receptors
      localization in human auditory cortex has been described recently, we explored in
      this study the hypothesis of an asymmetrical action of Bzd on MOC efferent
      functioning. The results revealed a significant difference of Bzd effect probing
      the right ear versus the left ear, with CAS-induced suppression being less
      effective in the right than left ear after oxazepam intake. This finding raises
      the question of possible neurochemical left-right asymmetry in the descending
      auditory pathways. The potential localization of this asymmetry is discussed.

PMID- 15993015
TI  - Traditional medicine and gastroprotective crude drugs.
AB  - A frequent question when dealing with the search for gastroprotective compounds
      from natural sources is how far or close are both the plant preparations and
      extract amounts from the doses recommended in traditional medicine and what
      should be considered realistic levels for experimental studies. The
      administration way is oral and therefore extracts and products should be
      administered by gavage when looking for validation of ethnopharmacological uses.
      Suggestions of doses for both crude extracts and pure compounds are presented and
      discussed. For plant extracts prepared from single herbs and herbal mixtures,
      dose-response studies in the range between 100 and 300 mg/kg are suggested, with
      more than a single gastric ulcer model either in rats or mice. A suitable
      reference compound should be used according to the ulcer model and in doses
      resembling those used for human patients. For pure compounds and structure
      activity studies or trends, dose-response results should be provided for at least
      a parent compound in order to select a reasonable dose for comparison purposes.
      We suggest an evaluation of the activity of the parent compound in the 50-300
      mg/kg range and to look for structural modification leading to derivatives with
      similar or higher gastroprotective effects than the reference antiulcer
      compounds.

PMID- 15993016
TI  - Chemical diversity of propolis and the problem of standardization.
AB  - Chemical variability of propolis is discussed with respect to the problem of
      standardization. Several chemical types of propolis are formulated, based on
      their plant source. Reliable criteria for chemical standardization of different
      propolis types are needed but such generally accepted criteria do not yet exist.
      The chemical profile of "poplar" propolis, typical for the temperate zone, can be
      characterized by the following parameters: total flavone and flavonol content,
      total flavanone and dihydroflavonol content, and total phenolics content. These
      parameters correlate better with the biological activity and are more informative
      that the quantification of individual components. There is still a lot of work to
      be done to achieve standardization of other propolis types. Working with
      standardized material will allow scientists to connect a particular chemical
      propolis type to a specific type of biological activity and formulate
      recommendations for mainstream practitioners.

PMID- 15993017
TI  - The future of ethnopharmacology: a southern African perspective.
AB  - The traditional use of medicinal plants in southern Africa is widespread with
      over 80% of South African households using medicinal plants. A mushrooming of
      research into the study of medicinal plants in the developing world has occurred
      but most of Africa is lagging behind in research output despite long traditions
      of medicinal plant usage. A considerable investment in research infrastructure is
      required.

PMID- 15993018
TI  - Importance of radiological diagnosis applied to necroscopy.
AB  - The authors evaluate the consequences of incomplete necroscopic examinations
      wherein it was impossible to apply radiological resources to locate firearm
      projectiles. The study includes 8185 reports from the Instituto Medico-Legal
      Afranio Peixoto in Rio de Janeiro, Brazil, representing the totality of corpses
      processed from January to December 2001; of these, 3122 were gunshot victims, 309
      of which were buried with unremoved projectiles, being liable to future judicial
      reappraisal. During the same period, there were 23 exhumation requests by police
      authorities, 12 of them querying the existence of projectiles. The authors looked
      into the formal reasons assumed by the medico legal experts to conclude their
      reports from incomplete examinations, and suggest that gunshot necroscopic
      examinations should follow specific protocols, as incomplete autopsies will
      require further exhumations, at unnecessary additional costs.

PMID- 15993019
TI  - Radiographic evaluation of teeth subjected to high temperatures: experimental
      study to aid identification processes.
AB  - The radiographic evaluation of dental remains represents a significant aspect in
      the forensic identification process, particularly after an exposure to fire. The
      aim of this "in vitro" study was to evaluate the radiographic features of
      unrestored, endodontically treated and restored teeth after exposure to an
      experimental range of high temperatures. Ninety human teeth were divided into two
      groups: (1) unrestored teeth, as a control group and (2) teeth endodontically
      treated (condensation technique) and restored with amalgam or composite fillings.
      Before testing the high temperatures, periapical radiographs of all teeth were
      performed. The tests of exposure to heat were carried out in an oven for six
      different temperatures (200, 400, 600, 800, 1000 and 1100 degrees C (392, 752,
      1112, 1472, 1832, 2012 degrees F)). After each exposure, periapical radiographs
      of all the teeth were taken. The radiographic appearance of all the teeth before
      and after the thermal stresses were evaluated and the differences were recorded.
      The results of the radiographic examination showed that a number of significant
      radiographic details were conserved: the composite fillings were in place
      maintaining the shape till 600 degrees C (1112 degrees F), the amalgam fillings
      were in place maintaining the shape till 1000 degrees C (1832 degrees F) and the
      endodontic treatments were recognisable till 1100 degrees C (2012 degrees F).

PMID- 15993020
TI  - Severe electrocution across the body escaping heart due to a third point of
      contact.

PMID- 15993021
TI  - A study concerning the blood/breath alcohol conversion factor Q: concentration
      dependency and its applicability in daily routine.
AB  - The conversion factor Q, obtained by division of blood alcohol concentration
      (BAC) by breath alcohol concentration (BrAC) is a widely discussed topic due to
      its great variance. By Austrian law, regulations frequently require an estimation
      of a corresponding BAC by a measured BrAC. It is known that Q depends among other
      things, on the alcohol kinetic state of the person being tested, which
      mathematically can be transformed to a dependency on the BrAC. Theoretically
      calculated Q values per BrAC level form a hyperbola shaped curve, thus decreasing
      with increasing BrAC values. Applying Austrian forensic standards for BAC and
      BrAC measurements, these calculations were verified in a study under practical
      conditions with BAC and BrAC data of 390 individuals. Q decreases from 2629 (+/-
      455) for BrAC levels < 0.1 mg/l to 2229 (+/- 160) for a BrAC range of 0.4-0.5
      mg/l and increases again to 2428 (+/- 124) for BrAC levels > 0.6 mg/l. Since
      these results were obtained under realistic practical conditions they can be
      directly applied in routine forensic expert opinion and can eliminate avoidable
      variances in the calculation of Q.

PMID- 15993022
TI  - Y-chromosome STR haplotype diversity in three ethnic populations in Singapore.
AB  - In this study, 12 Y-STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392,
      DYS393, DYS385a/b, DYS437, DYS438 and DYS439) were genotyped in the three major
      ethnic populations in Singapore, namely the Chinese, Malay and Indian. Allele
      frequency distribution, locus diversity, haplotype diversity and discrimination
      capacity were estimated. Analysis of molecular variance between the three ethnic
      populations indicated that 87.71% of the haplotypic variation is found within
      population and 12.29% is between populations (Fixation Index FST=0.123, p=0.000).
      Population pairwise comparisons showed significant Phist values between all
      population pairs, with the lowest (RST=0.05) for Chinese-Malay and the highest
      (RST=0.19) for Chinese-Indian.

PMID- 15993025
TI  - Principles of tumor imaging.
AB  - Tumors involving the upper extremity are not uncommon. Although there is a wide
      variety of lesions that may occur in the hand and wrist, there are certain
      lesions which have a predilection for this location. This chapter will highlight
      the spectrum of imaging modalities available for the evaluation of upper
      extremity tumors, providing imaging guidelines for optimum selection of
      radiological examinations. It presents an overview of imaging of the hand and
      wrist, emphasizing the fundamental principles inherent to tumor imaging.
      Modalities reviewed include nuclear scintigraphy, positron emission tomography,
      sonography, computed tomography, arteriography, magnetic resonance imaging, and
      magnetic resonance angiography.

PMID- 15993026
TI  - Detection of modafinil in human urine by gas chromatography-mass spectrometry.
AB  - The main purpose of this study was to detect and quantify modafinil in human
      urine by gas chromatography-mass spectrometry (GC-MS). Urinary samples were
      collected from three healthy male volunteers following oral administration of a
      clinical dose (100 mg) of modafinil (Provigil). Urine specimens were extracted
      with t-butylmethyl ether (TBME) prior to GC-MS analysis. The results demonstrate
      that the chromatographic characteristics and the mass spectrum of the unchanged
      parent drug extracted from urine samples were identical to that obtained from the
      authentic standard. The times for the unchanged modafinil to reach peak
      concentration in the urine of the three volunteers were at 2 h (6.14 microg/mL),
      4 h (9.93 microg/mL) and 8 h (3.58 microg/mL), respectively. Total clearance
      occurred in approximately 48-72 h with 2-5% eliminated through urine as unchanged
      modafinil. The present study demonstrates that modafinil is detectable in the
      absence of hydrolysis and derivatization steps.

PMID- 15993027
TI  - Microvessel density does not predict outcome in high grade soft tissue sarcoma.
AB  - The induction of new blood vessel growth into tumours from a pre-existing
      vascular bed (angiogenesis) is a characteristic of virtually all malignant
      tumours studied. Previous studies have demonstrated a consistent correlation
      between the extent of angiogenesis and disease prognosis for a wide range of
      carcinomas, but not for sarcomas. AIMS: To investigate the most appropriate
      method for assessment of microvessel density (MVD) using a cohort of patients
      with large (>5 cm), deep (intramuscular), high grade soft tissue sarcoma and
      investigate any relationship between MVD, vascular endothelial growth factor
      (VEGF) expression and prognosis. METHODS: Forty-two patients were included in the
      study. MVD was evaluated in peripheral, central, necrotic and hotspot areas
      within the tumour by either Chalkley count or total count of immunostained
      vessels in five high power (x 200) visual fields. RESULTS: Hot spots of
      angiogenesis were only present in 33% of specimens. There was a strong
      correlation p<0.001 between the two methods of quantification with Chalkey method
      being recommended. VEGF expression evaluated by immunohistochemistry was seen in
      all but one tumour with strong diffuse cytoplasmic staining within tumour cells,
      which was not correlated with microvessel density, metastasis or survival. There
      was a positive correlation between MVD and histological subtype (p<0.01), and
      primary tumour size and the development of metastasis (p=0.049) but MVD was not
      predictive of metastasis or overall survival. CONCLUSIONS: Unlike the majority of
      previous studies involving various types of carcinoma, there was no correlation
      between microvessel density and metastasis or survival in a group of patients
      with large (>5 cm), deep, high grade soft tissue sarcoma.

PMID- 15993028
TI  - Continued axillary sampling is unnecessary and provides no further information to
      sentinel node biopsy in staging breast cancer.
AB  - INTRODUCTION: Sentinel lymph node biopsy (SLNB) has become increasingly accepted
      as a diagnostic method to stage the axilla in breast cancer, selecting women with
      a positive sentinel node for completion axillary clearance. As SLNB became
      established, many surgeons supplemented SLNB to sample a minimum of four lymph
      nodes, on the assumption that the four-node technique is supported by randomised
      trial data. We hypothesised that the practice of undirected sampling to
      supplement SLNB adds little information to the status of the residual axilla.
      METHODS: One hundred and sixty-five patients with early breast cancer were
      studied. Following successful identification of the sentinel node, 84 women had
      completion axillary dissection and 81 women had an axillary sample with at least
      four nodes available for pathological assessment. RESULTS: Following successful
      identification of the sentinel node in 165 patients, the false negative rate
      (FNR) was 2/44=4.5% (95% CI 0.6-15.5), sensitivity 42/44=95.5% (84.5-99.4) and
      negative predictive value (NPV) 121/123=98.4% (94.2-99.8). In the axillary
      dissection cohort, the FNR was 2/26=7.7% (0.9-25.1), sensitivity 24/26=92.3%
      (74.9-99.1) and NPV 58/60=96.7% (88.5-100). In the axillary sample group, the FNR
      was 0/18=0% (0-18.5), sensitivity 18/18=100% (81.5-100) and NPV 63/63=100% (94.3
      100). The SLNB was the only positive node in 12/26 (46.2%) in the axillary
      dissection group and 10/18 (55.6%) in the axillary sampling group. There was no
      patient in the axillary sampling group where the sample node was positive and the
      sentinel node negative. CONCLUSION: Once SLNB is validated within the
      multidisciplinary unit, undirected sampling of the axilla following
      identification of the sentinel node(s) is unnecessary. The additional sampling of
      non-sentinel nodes has no role to play either in the assessment of a potential
      false negative SLNB nor as predictive information on the status of the residual
      axillary nodes.

PMID- 15993029
TI  - Morbidity after axillary sentinel lymph node biopsy in patients with cutaneous
      melanoma.
AB  - AIM: In this study, the short-term and long-term morbidity was assesed after
      axillary sentinel lymph node biopsy (SLNB) with or without completion axillary
      lymph node dissection (SLNB/ALND) in patients with cutaneous melanoma. METHODS:
      Between 1995 and 2003, 119 axillary SLNBs were performed for cutaneous melanoma.
      Fifty-eight patients met the inclusion criteria and entered the study. RESULTS:
      Forty-four patients underwent SLNB alone and 14 patients underwent axillary lymph
      node dissection after positive SLNB. Complications after SLNB alone: post
      operative bleeding (n=2), seroma (n=1) and slight lymphedema 11%. Complications
      after SLNB/ALND: wound infections (n=2), seroma (n=5) and slight lymphedema 7%.
      There were differences between the two groups in short-term complications
      (p<.001) and functional limitations of the shoulder (p=.011). CONCLUSION:
      Axillary SLNB alone had a low complication rate. However, SLNB followed by
      completion ALND was associated with an increased risk of short- and long-term
      complications.

PMID- 15993030
TI  - Cyclin D1 protein and CCND1 gene expression in colorectal cancer.
AB  - AIMS: To report the expression of cyclin D1 protein and its gene in a series of
      colorectal adenocarcinoma. METHODS: One hundred and eleven specimens of
      colorectal carcinomas and adjacent normal colorectal mucosa were investigated by
      staining with a monoclonal antibody against cyclin D1 and by RT-PCR. RESULTS:
      Expression of CCND1 gene was found in 54 out of 111 cases of colorectal cancers,
      while in normal mucosa the expression of this gene was not observed. Cyclin D1
      protein expression was checked in the same group of adenocarcinoma cases.
      Presence of this protein was observed in 69 cases and for 43 of them also
      expression of its gene was found. Dependence between the presence of protein and
      the gene expression was statistically significant (p=0.0002). In the group of
      cases where CCND1 gene expression was detected, high level of its protein
      expression was found in 20 cases. The CCND1 gene expression was associated with
      metastases to lymph nodes (p=0.0181) and also with distant metastasis (p=0.0204).
      CONCLUSIONS: The combined measurement of both the gene and its protein product,
      is an important contribution to the study of molecular markers in histological
      material.

PMID- 15993031
TI  - Comparative study of survival of patients with hepatocellular carcinoma predicted
      by different staging systems using multivariate analysis.
AB  - AIMS: In a previous pilot study, we reported the usefulness of the modified the
      Cancer of the Liver Italian Program (CLIP) score for patients with hepatocellular
      carcinoma (HCC). To determine the best staging system for predicting the survival
      of HCC patients, we conducted a comparative analysis of prognosis using
      multivariate analysis in 210 Japanese HCC patients who underwent hepatic
      resection. METHODS: We compared the survival as predicted by various staging
      systems, including tumour node metastasis (TNM) stage of the American Joint
      Commission on Cancer (AJCC) and the Liver Cancer Study Group of Japan, the Japan
      Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), CLIP
      score and our modified CLIP score using protein induced by vitamin K absence or
      antagonist II (PIVKA-II). RESULTS: Univariate analysis showed that discrimination
      of disease-free survival in the early and advanced stages by the JIS score and
      modified CLIP score was clearer than by the Japanese or AJCC TNM or the original
      CLIP score. Discrimination between stages of overall survival by all staging
      systems was significant. Multivariate analysis showed that the JIS, CLIP and
      modified CLIP scores were better staging systems for predicting survival than the
      Japanese and AJCC TNM. The modified CLIP score showed the lowest Akaike
      information criteria statistical value for disease-free and overall survival,
      which means the best discrimination ability for patient survival compared with
      the JIS score and CLIP score. CONCLUSIONS: A staging system that combines tumour
      factors, sensitive tumour marker(s) and hepatic function is the best predictor of
      prognosis of HCC patients.

PMID- 15993032
TI  - Protein S in cancer patients with non-metastatic solid tumours.
AB  - AIMS: To study protein S, as an acute phase protein, for its relationships with
      C4b-BP (C4BP), fibrinogen and Factor VIII:C in a group of patients with solid
      tumours, without proven metastases. METHODS: Eighty-one consecutive patients with
      gastrointestinal or pelvic adenocarcinoma (TNM staging: T1-3, N0-2, M0) and 58
      healthy subjects were evaluated for plasma free and total protein S antigen,
      protein S activity, C4BP, fibrinogen and Factor VIII:C. RESULTS: When compared to
      the control group, the total protein S, the C4BP, the fibrinogen and the Factor
      VIII:C mean levels were significantly higher in the cancer group, but there was
      no significant difference for the free and the functional protein S mean
      concentrations. In both groups the free protein S was correlated with the
      functional and the total protein S; moreover the latter was significantly
      correlated with the C4BP, whereas it was significantly correlated with the
      fibrinogen and the Factor VIII:C only in the cancer group. In addition, a high
      correlation was found among the C4BP, the fibrinogen and the Factor VIII:C.
      CONCLUSIONS: Our data show that in these patients there is an acute phase
      response and suggest that, in the thrombophilic early cancer screening,
      determination of free protein S is redundant.

PMID- 15993033
TI  - Transcriptome analysis of rat liver regeneration in a model of oval hepatic stem
      cells.
AB  - We have performed serial analysis of gene expression of the regenerating liver.
      In the rat model of partial hepatectomy and 2-acetamidofluorene treatment liver
      regeneration recruits hepatic stem cells referred to as oval cells. We analyzed a
      total of 153,057 tags in livers from normal control (52,343 tags), from sham 2
      acetamidofluorene-treated control (50,502 tags), and from the early stage of oval
      cell proliferation (50,212 tags). Comparative analysis of the three
      transcriptomes identified 27 up-regulated and 18 down-regulated genes. Real-time
      PCR analysis confirmed 11 temporally regulated genes that correlate with oval
      cell development. Interestingly, we found by Western blot protein analysis of
      regenerating livers that the cell cycle gene Cdc42 was induced concomitant with
      the proliferation marker cyclin D1 and the oval cell marker alpha-fetoprotein.
      Our studies provide new insights into the molecular mechanism of liver
      regeneration through oval cells.

PMID- 15993034
TI  - Role of poly(A) tail length in Alu retrotransposition.
AB  - Alu are mobile noncoding Short INterspersed Elements (SINEs) present at a million
      copies in the human genome. Using marked Alu sequences in an ex vivo assay, we
      previously showed that they are mobilized through diversion of the LINE (Long
      INterspersed Elements) retrotransposition machinery, with the poly(A) tail of the
      Alu being required for their mobility. Here we show that other homopolymeric
      tracts cannot functionally replace the Alu poly(A) tail, and that the Alu
      transposition rate varies over a two-log range depending on the poly(A) tail
      length. Variation is according to a sigmoid-shaped curve with a lag observed for
      tails shorter than 15 nt and a plateau reached for tails longer than 50 nt,
      consistent with the binding of a limited number of a protein component requiring
      multiple contacts for a productive interaction with the poly(A) stretch. This
      analysis indicates that most of the naturally occurring genomic Alu, owing to
      their pA tail length, should be poor substrates for the LINE machinery, a feature
      possibly "selected" for the host sake.

PMID- 15993035
TI  - Development of multidrug resistance type I P-glycoprotein function during in
      vitro maturation of porcine oocyte.
AB  - The present study was performed to evaluate the expression and function of P
      glycoprotein (P-gp) encoded the multidrug resistance type I (MDR1) gene,
      protecting from xenotoxics, in porcine oocyte during in vitro maturation. Cumulus
      oocyte complexes (COCs) were cultured to obtain the germinal vesicle (GV), first
      metaphase and second metaphase (MII) oocytes. The P-gp function was assessed by
      means of the rhodamine 6G (R6G) efflux from oocytes with P-gp inhibitors such as
      verapamil and PSC-833. The MDR1 transcript was detected in the GV and MII oocytes
      by RT-PCR analysis using primer sets based on the human gene. P-gp inhibitors
      significantly blocked the R6G efflux from the MII oocytes, whereas the reagents
      were ineffective in the GV oocytes. The R6G efflux from oocytes was accelerated
      at the MII stage more than at the GV stage. Thus, the MDR1-type P-gp function is
      poor at the GV stage, but the function improves during oocyte maturation.

PMID- 15993036
TI  - Stochastic complexities of reduced rank regression in Bayesian estimation.
AB  - Reduced rank regression extracts an essential information from examples of input
      output pairs. It is understood as a three-layer neural network with linear hidden
      units. However, reduced rank approximation is a non-regular statistical model
      which has a degenerate Fisher information matrix. Its generalization error had
      been left unknown even in statistics. In this paper, we give the exact asymptotic
      form of its generalization error in Bayesian estimation, based on resolution of
      learning machine singularities. For this purpose, the maximum pole of the zeta
      function for the learning theory is calculated. We propose a new method of
      recursive blowing-ups which yields the complete desingularization of the reduced
      rank approximation.

PMID- 15993037
TI  - Autoreactive responses to environmental factors: 3. Mouse strain-specific
      differences in induction and regulation of anti-DNA antibody responses due to
      phthalate-isomers.
AB  - Little is known of the role of specific environmental factors in promoting
      autoimmune disorders such as systemic lupus erythematosus (SLE). This study
      addresses how exposure to phthalates, common environmental factors in foods, and
      biomedical devices could affect the immune functions of resistant and autoimmune
      prone mice. We have previously shown that immunization with ortho-phthalate
      evokes anti-DNA antibody in BALB/c and NZB/W F1 mice, but only the latter suffer
      from nephritis and high mortality. BALB/c mice, in contrast, develop idiotype
      specific CD8+ suppressor T cells downregulating autoreactive B cells. Here we
      report that all phthalate-isomers (ortho-, meta- and para-) are capable of
      inducing anti-DNA antibody responses and SLE-like syndromes. Kidney pathology
      worsens in NZB/W F1 and to a degree, in C57BL/6 mice after repeated exposure to
      phthalates. Only BALB/c and DBA/2 overcome adverse autoreactivity by induction of
      Ts cells; but in vivo depletion of these T cells renders these strains
      susceptible to autoreactivity. Anti-DNA antibodies in affected NZB/W F1 are
      largely IgG2a-type, while in BALB/c, DBA/2, and C57BL/6 mice IgG1-type. This is
      further corroborated by cytokine analyses that imply corresponding Th1/Th2
      involvement. In summary, the commonly used phthalates appear harmful to
      susceptible strains, while BALB/c and DBA/2 are spared due to induction of Ts
      cells.

PMID- 15993038
TI  - The neuropeptide pituitary adenylate cyclase activating protein is a
      physiological activator of human monocytes.
AB  - Pituitary adenylate cyclase activating protein (PACAP) and its structurally
      related vasointestinal peptide (VIP) bind to three G-protein-coupled receptors
      named VPAC1 and VPAC2 for VIP/PACAP receptors and PAC1 for PACAP preferred
      receptors. We report that in freshly isolated human monocytes PACAP acts as a pro
      inflammatory molecule. By RT-PCR, VPAC1 mRNA was the only receptor found to be
      expressed; VPAC1 protein was detected by Western blotting and visualized by
      immunohistochemistry. Signaling pathways activated by PACAP include the
      extracellular regulated kinase (ERK), the stress-activated MAPK p38, the focal
      adhesion kinase, Pyk2 and its associated cytoskeleton protein paxillin and the
      phosphatidylinositol 3-kinase (PI-3K). PACAP induces a transient peak in
      cytoplasmic calcium associated with an increase in reactive oxygen species
      production and upregulation in membrane expression of the integrin CD11b as well
      as the complement receptor 1. Control of the different pathways and functions
      stimulated by PACAP were evaluated using Phospholipase C (PLC), PI-3K, ERK and
      p38 MAPK inhibitors and led to the conclusion that PLC and to a lesser degree PI
      3K activation are upstream events occurring in VPAC1 mediated PACAP stimulation
      of monocytes and are in contrast to ERK and p38 mandatory for the initiation of
      other cellular events associated with monocytes activation.

PMID- 15993039
TI  - RhoA-mediated Phospholipase D1 signaling is not required for the formation of
      stress fibers and focal adhesions.
AB  - The small GTPase RhoA regulates a wide spectrum of cellular functions including
      transformation and cytoskeletal reorganization. A large number of proteins have
      been identified as targets of RhoA, but their specific roles in these processes
      are not clear. Phospholipase D (PLD) was shown to be one such target several
      years ago; more recent work from our laboratory and others has demonstrated that
      of the two mammalian PLD isozymes, PLD1 but not PLD2 is activated by RhoA and
      this activation proceeds through direct binding both in vitro and in vivo. In
      this study, using a series of RhoA mutants, we have defined a PLD1-specific
      interacting site on RhoA composed of the residues Asn41, Trp58 and Asp76, using
      the yeast two-hybrid system, co-immunoprecipitation, and a PLD in vivo assay. The
      results further substantiate our previous finding that RhoA activates PLD1
      through direct interaction. These mutants were then used to investigate the role
      of PLD1 in the cytoskeletal reorganization stimulated by RhoA signaling. Our
      results show that PLD1 is not required for the RhoA-mediated stress fiber and
      focal adhesion formation. The lack of importance of PLD1 signaling in RhoA
      mediated cytoskeletal reorganization is further supported by the observation that
      PLD1 depletion using an shRNA approach and tetracycline-induced overexpression of
      the wild-type and the catalytically inactive mutant of PLD1 in stable cell lines
      do not alter stress fiber and focal adhesion formation.

PMID- 15993040
TI  - Involvement of glycogen synthase kinase-3beta in hydrogen peroxide-induced
      suppression of Tcf/Lef-dependent transcriptional activity.
AB  - Hydrogen peroxide (H(2)O(2)) mediates induction of cytotoxicity in various cell
      types. GSK-3beta has been found to participate in a number of signaling pathways,
      including cell proliferation and cell death. In the present study, we show that
      GSK-3beta is rapidly dephosphorylated and activated in response to H(2)O(2)
      treatment. H(2)O(2) also dephosphorylates Akt/PKB in a dose- and time-dependent
      manner. Overexpression of Akt/PKB attenuates H(2)O(2)-induced dephosphorylation
      of GSK-3beta. Ectopic expression of Dvl-1, a component of Wnt signaling,
      stimulates Akt/PKB and inhibits dephosphorylation of GSK-3beta by H(2)O(2).
      Furthermore, H(2)O(2) causes the reduction of beta-catenin level and LiCl
      mediated activation of Tcf/Lef-dependent transcription activity. These findings
      suggest that GSK-3beta is involved in H(2)O(2)-mediated inhibition of Tcf/Lef
      dependent transcriptional activity.

PMID- 15993041
TI  - Waist circumference criteria for the diagnosis of abdominal obesity are not
      applicable uniformly to all populations and ethnic groups.
AB  - Determination of cutoff points of waist circumference is of paramount importance
      for prevention, optimum management, and prognostication of obesity, the metabolic
      syndrome, type 2 diabetes mellitus, and coronary heart disease. Heterogeneity of
      composition of abdominal tissues, in particular adipose tissue and skeletal
      muscle, and their location-specific and changing relations with metabolic factors
      and cardiovascular risk factors in different ethnic groups do not allow a simple
      definition of abdominal obesity that could be applied uniformly. In particular,
      Asians appear to have higher morbidity at lower cutoff points for waist
      circumference than do white Caucasians. International health agencies that deal
      with obesity (World Health Organization, International Obesity Task Force) should
      take cognizance of these data and consider formulating new cutoff points for
      waist circumference to define abdominal obesity for Asian populations.

PMID- 15993042
TI  - Hand preferences for unimanual and coordinated bimanual tasks in baboons (Papio
      anubis).
AB  - This study examined hand preference in baboons in a sample of 94 subjects for a
      unimanual task and in a sample of 104 subjects for a bimanual task. For the
      unimanual task, handedness was assessed by observing simple reaching for grains.
      For the bimanual task, tubes lined with peanut butter inside were presented to
      the baboons. The hand and the finger used to remove peanut butter were recorded.
      Population-level right-handedness was found for the bimanual but not the
      unimanual task. In addition, test-retest correlations showed consistency in hand
      use across time for the coordinated bimanual task but not the simple reaching
      task. No significant effects of age and sex on the direction and strength of hand
      preferences were found for either task. These are the first evidences of
      population-level handedness in baboons and the results are discussed in the
      context of evolutionary theories of cerebral dominance.

PMID- 15993043
TI  - [Diagnostic strategies for ischemic strokes in childhood].
AB  - Ischemic strokes represent a rare condition in childhood, mostly revealed by a
      motor deficit. In the pediatric age, strokes are different than in adulthood
      where atherosclerosis is the major cause. The etiologies of stroke in childhood
      are rather multiple and each of them is rare. In nearly half of the pediatric
      cases no cause can be found and usually no recurrence occurs. The aim of this
      presentation is to propose a diagnosis strategy for ischemic strokes in children.
      An extensive search should be performed in every children presenting a stroke
      episode even if the initial outcome appears favorable. Such investigations could
      improve our understanding and therapeutic strategies of stroke in childhood, a
      condition where the cognitive and functional prognosis can be severely
      compromised.

PMID- 15993044
TI  - [Body temperature measurement in daily practice].
AB  - The use of rectal mercury thermometer has long been the standard method for
      measurement of body temperature. The restriction of mercury use since 1996 has
      led to development of other devices. The liquid crystal strip thermometer held
      against the forehead has a low sensitivity. The single-use chemical thermometer
      measures oral temperature. Its accuracy must be evaluated. Infrared ear
      thermometers are routinely used because it is convenient and fast to use.
      However, numerous studies have shown that it does not show sufficient correlation
      with rectal temperature, leading to the risk to miss cases of true fever. Rectal
      temperature remains the gold standard in case of fever. Rectal temperature
      measurement with an electronic device is well correlated with the glass mercury
      standard. Galistan thermometer accuracy must be evaluated because of
      sterilization of the whole device, which is not the case for the electronic
      thermometer. A pediatric study is necessary to evaluate the performance of this
      device in comparison with the electronic thermometer.

PMID- 15993045
TI  - Part-whole representation and reasoning in formal biomedical ontologies.
AB  - OBJECTIVE: Biomedical ontologies are typically structured in a biaxial way,
      reflecting both a taxonomic (is-a) and a partonomic (part-of) hierarchy. Commonly
      used biomedical terminologies, which incorporate such distinctions excel in terms
      of broad coverage but lack a rigid formal foundation. The latter, however, is a
      prerequisite for automated reasoning. For the biomedical domain, it is not only
      crucial to cope with ontological dependencies between wholes and their parts but
      also with specific reasoning patterns which underlie the propagation of roles
      across partonomic hierarchies. METHODS: We scale down part-whole reasoning to
      subsumption-based taxonomic reasoning within the formal framework of a
      parsimonious variant of description logics (viz. ALC). RESULTS: We provide a
      formal basis for ontological engineering in the domain of biomedicine, as far as
      part-whole relationships are concerned, by addressing typical reasoning patterns
      encountered in this domain.

PMID- 15993046
TI  - The interface behavior and biocatalytic activity of superoxide dismutase at
      carbon nanotube.
AB  - The interface behavior and biocatalytic activity of superoxide dismutase (SOD)
      were studied at carbon nanotube (CNT) surface with cyclic voltammetry (CV). The
      results show that SOD participates in a rapid exchange with CNT and the process
      is a single-electron-single-proton process. The electron-transfer coefficient was
      calculated to be 0.52, the electron-transfer rate constant was 1.4s(-1) and the
      average surface coverage was measured to be 6.93 x 10(-11)+/-4.2 x 10(-12) mol
      cm(-2). The bioactive measurements show that SOD keeps its bioactivity at the CNT
      surface. SOD's remarkable ability to catalyze the dismutation of the superoxide
      anion (O (2)(-)) has been demonstrated.

PMID- 15993047
TI  - Sane in the membrane: designing systems to modulate membrane proteins.
AB  - Proteins and lipids make sense in rational approaches to the design of systems
      for the study of membrane proteins. Lipids surround integral membrane proteins in
      their natural environment. Although lipids have always formed part of
      investigations into membrane proteins, it has generally been the proteins
      themselves that have taken the limelight. As knowledge of membrane proteins has
      increased, so has that of their interactions with lipids. This increased
      understanding of the interplay of proteins and lipids, together with existing
      knowledge of lipid properties, is enabling new approaches to be introduced for
      membrane protein study. The lipids can be used to control protein behaviour and
      as novel probes of protein motion.

PMID- 15993048
TI  - Estrogen A-ring structure and antioxidative effect on lipoproteins.
AB  - The oxidative modification of lipoprotein particles is an important step in
      atherogenesis. Estrogens are known to be powerful antioxidants independently of
      their binding to the estrogen receptors and the hormonal functions. We explored
      the structural determinants for the antioxidant activity of a large number of
      estrogen derivatives (n=43) in an aqueous lipoprotein solution in vitro by
      monitoring formation of conjugated dienes. Our results indicate that estrogen
      derivatives with an unsubstituted A-ring phenolic hydroxyl group with one or two
      adjacent methoxy groups provide strongest antioxidant protection of low density
      lipoprotein (LDL) and high density lipoprotein (HDL). The electron donating
      methoxy groups may enhance the antioxidant effect by weakening the phenolic OH
      bond and providing stability to the formed phenoxyl radical. With some
      exceptions, compounds completely lacking unsubstituted hydroxyl groups in the A
      ring exhibited no antioxidant effect, e.g. the most hydrophilic "tetrol" compound
      with three unsubstituted A-ring hydroxyl groups had no antioxidant effect.
      Moreover, additional hydroxyl groups in the B-, C- or D-ring seemed to weaken the
      antioxidant effect. Accordingly, both the presence of unsubstituted hydroxyl
      groups and adjacent substituents, as well as the lipophilicity of the derivatives
      determine the antioxidant activity of estrogen derivatives in aqueous lipoprotein
      solutions.

PMID- 15993049
TI  - 5alpha-Reductase activity in Lycopersicon esculentum: cloning and functional
      characterization of LeDET2 and evidence of the presence of two isoenzymes.
AB  - The full-length cDNA (LeDET2) encoding a 257 amino acid protein homolog of
      Arabidopsis DET2 (AtDET2) was isolated in tomato (Lycopersicon esculentum).
      LeDET2 has 76% similarity with AtDET2 and structural characteristics conserved
      among plant and mammalian steroid 5alpha-reductases (5alphaRs). LeDET2 is
      ubiquitously expressed in tomato tissues with higher levels in leaf than in stem,
      root, seed and callus. When expressed in mammalian cells (COS-7), recombinant
      LeDET2 was active on substrates typical of mammalian 5alphaRs (progesterone,
      testosterone, androstenedione), but reduced at very low levels campestenone, the
      substrate described for AtDET2. Similar results were obtained with the expression
      in COS-7 of recombinant AtDET2 that showed 5alphaR activity for progesterone and
      not for campestenone. Recombinant LeDET2 was inhibited by several inhibitors of
      the human 5alphaRs and the application of an active inhibitor to tomato seedlings
      induced dwarfism and morphological changes similar to BR-deficient mutants. In
      tomato tissues, campestenone was 5alpha-reduced in leaf, stem and root
      homogenates, like progesterone and testosterone, while androstenedione was
      converted to testosterone, evidencing for the first time a 17beta-hydroxysteroid
      dehydrogenase activity in plants. Moreover, two separate 5alphaR activities with
      different kinetic characteristic and response to inhibitors were characterized in
      tomato tissues. The presence of two 5alphaR isoenzymes was demonstrated also in
      Arabidopsis using the det2-1 mutant, in which a residual 5alphaR activity for
      campestenone and progesterone was evidenced and characterized. Therefore, the
      existence of two isoenzymes of 5alphaR is probably characteristic of the whole
      plant kingdom highlighting the similarities between the animal and plant steroid
      biosynthetic pathways.

PMID- 15993050
TI  - Plasma cell neoplasms. Review of disease progression and report of a new variant.
AB  - Plasma cell neoplasms are generally categorized into four groups; multiple
      myeloma (MM), solitary plasmacytoma of the bone (SPB), plasma cell leukemias, and
      extramedullary plasmacytomas (EMP). A plasmacytoma is defined as any discrete,
      usually solitary mass of neoplastic plasma cells, either in the bone marrow or in
      various soft tissue sites. Each manifestation of a plasma cell neoplasm differs
      in terms of tumor recurrence and progression to MM. A gastric plasmacytoma (GP)
      is a rare presentation of extramedullary plasmacytoma and has not been previously
      reported as a site of recurrence for a SPB. This pattern of tumor recurrence is
      unique and the management of gastric plasmacytoma as part of this complex disease
      is discussed. The continuum of progression between various sites and
      manifestations of plasma cell manifestations is reviewed including a previously
      undiscovered sequence of bone disease, gastric disease, and finally multiple
      myeloma.

PMID- 15993051
TI  - The role of surgery in the management of gastrointestinal stromal tumors (GISTs)
      in the era of imatinib mesylate effectiveness.
AB  - Surgical resection is the treatment of choice for the gastrointestinal stromal
      tumors (GISTs). In the literature, the 5-year patient survival after surgical
      resection, ranged from 48 to 80%, before the era of imatinib mesylate and the
      exploration of the prognostication criteria. Imatinib mesylate targets an
      intracellular signaling molecule of the natural history and malignant development
      of GISTs, and increased the 5-year survival rate, after the resection of primary
      low-risk GISTs, to similar values to the normal population. For high-risk GISTs,
      current knowledge which is still under expansion, show major improvement at the 1
      year survival rate of more than 90% versus less than 50% before imatinib era.
      After surgical resection, for both low and high malignant potential GISTs, a
      closed control directed to the early identification of confined resectable
      recurrences, is required. This paper assesses the current knowledge of GIST
      management, motivated by a case of patient with intermediate risk GIST.

PMID- 15993052
TI  - Non-conventional low-cost adsorbents for dye removal: a review.
AB  - Adsorption techniques are widely used to remove certain classes of pollutants
      from waters, especially those that are not easily biodegradable. Dyes represent
      one of the problematic groups. Currently, a combination of biological treatment
      and adsorption on activated carbon is becoming more common for removal of dyes
      from wastewater. Although commercial activated carbon is a preferred sorbent for
      color removal, its widespread use is restricted due to high cost. As such,
      alternative non-conventional sorbents have been investigated. It is well-known
      that natural materials, waste materials from industry and agriculture and
      biosorbents can be obtained and employed as inexpensive sorbents. In this review,
      an extensive list of sorbent literature has been compiled. The review (i)
      presents a critical analysis of these materials; (ii) describes their
      characteristics, advantages and limitations; and (iii) discusses various
      mechanisms involved. It is evident from a literature survey of about 210 recent
      papers that low-cost sorbents have demonstrated outstanding removal capabilities
      for certain dyes. In particular, chitosan might be a promising adsorbent for
      environmental and purification purposes.

PMID- 15993053
TI  - Purification of siderophores of Alcaligenes faecalis on Amberlite XAD.
AB  - Studies on siderophore production using Alcaligenes faecalis BCCM ID 2374
      revealed hydroxamate and catecholate type of siderophores at 347 microg mL-1.
      These fractions were purified on Amberlite XAD-4 column, which resulted in the
      separation of two bands having absorption maxima at 264 and 224 nm. The amount of
      pure siderophore obtained in powdered form from first and second fraction was 297
      and 50 microg mL-1 respectively.

PMID- 15993054
TI  - Synthesis and antibacterial activity of alkyl derivatives of the glycopeptide
      antibiotic A40926 and their amides.
AB  - New derivatives of the glycopeptide antibiotic A40926 were synthesized and
      evaluated for antimicrobial activity against VRE. Deacylated A40926 was obtained
      by microbial transformation of the parent antibiotic with the use of Actinoplanes
      teichomyceticus ATCC 31121. Regioselective synthesis of alkylated derivatives of
      Deacyl A40926 was carried out using lipophilic aliphatic and aromatic halides or
      aldehydes. Further modification of the two carboxylic acids was performed to
      increase antibiotic activity. Poor antimicrobial activity was observed for the
      derivatives obtained by lipophilic mono- or dialkylation of the amino groups
      present on the molecule, while simultaneous condensation of both carboxylic
      groups, in hydrophobic derivatives, with dibasic amines led to a strong increase
      in antibiotic activity.

PMID- 15993055
TI  - Comparison of different heterocyclic scaffolds as substrate analog PDE5
      inhibitors.
AB  - Several different heterocyclic systems were compared as PDE5 inhibitor scaffolds.
      In addition to the known 3H-imidazo[5,1-f][1,2,4]triazin-4-ones and
      pyrazolopyrimidinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones were also
      shown to be potent and selective PDE inhibitor scaffolds with in vivo activity.
      SAR trends were elucidated for sulfonamide derivatives with generality across
      different scaffolds.

PMID- 15993056
TI  - A physicogenetic method to assign ligand-binding relationships between 7TM
      receptors.
AB  - A computational protocol has been devised to relate 7TM receptor proteins (GPCRs)
      with respect to physicochemical features of the core ligand-binding site as
      defined from the crystal structure of bovine rhodopsin. The identification of
      such receptors that already are associated with ligand information (e.g., small
      molecule ligands with mutagenesis or SAR data) is used to support structure
      guided drug design of novel ligands. A case targeting the newly identified
      prostaglandin D2 receptor CRTH2 serves as a primary example to illustrate the
      procedure.

PMID- 15993057
TI  - Identification of potent type I MetAP inhibitors by simple bioisosteric
      replacement. Part 1: Synthesis and preliminary SAR studies of thiazole-4
      carboxylic acid thiazol-2-ylamide derivatives.
AB  - A series of thiazole-4-carboxylic acid thiazol-2-ylamide (TCAT, 4) derivatives
      were designed and synthesized according to simple bioisosteric replacement from
      previously reported pyridine-2-carboxylic acid thiazol-2-ylamide (PCAT) MetAP
      inhibitors. The preliminary SAR studies demonstrated that these TCAT series of
      compounds showed different activity and selectivity compared with those of the
      corresponding PCAT compounds. These findings provide useful information for the
      design and discovery of more potent inhibitors of type I MetAPs.

PMID- 15993058
TI  - Effects of B group vitamins on reactions of various alpha-hydroxyl-containing
      organic radicals.
AB  - Effects of vitamins B1, B2, B6, and pyridoxal phosphate (PPh) on final product
      formation in radiolysis of aqueous solutions of ethanol, ethylene glycol, alpha
      methylglycoside, and maltose were studied. It has been found that vitamin B2 and
      PPh effectively oxidize R*CHOH species, while suppressing their recombination and
      fragmentation reactions, thereby increasing the yields of the respective
      oxidation products. Vitamins B1 and B2 are capable of reducing alcohol radicals
      to the respective initial molecules, decreasing the yields of the radical
      transformation products.

PMID- 15993059
TI  - L-arginine analogs as alternate substrates for nitric oxide synthase.
AB  - The L-arginine analogs, N(delta)-methyl-L-arginine (deltaMA) and L-canavanine,
      were used to probe the role of the N delta nitrogen of L-arginine in the reaction
      catalyzed by nitric oxide synthase (NOS). deltaMA was synthesized and found to be
      a partial alternate substrate and a weak, reversible inhibitor of NOS with a Ki
      equal to 1.4 mM. deltaMA undergoes hydroxylation; however, it is not converted
      further, hence it functions as a partial substrate. L-Canavanine was converted to
      an L-homoserine presumably via initial hydroxylation and decomposition. The
      mechanism of this reaction and products of this reaction were not probed further.

PMID- 15993060
TI  - Discovery and in vitro evaluation of potent kinase inhibitors:
      Pyrido[1',2':1,5]pyrazolo[3,4-d]pyrimidines.
AB  - The discovery, synthesis, potential binding mode, and in vitro kinase profile of
      several pyrido[1',2':1,5]pyrazolo[3,4-d]pyrimidines as potent kinase inhibitors
      are discussed.

PMID- 15993061
TI  - Microwave-assisted synthesis of imidazoles: reaction of p-toluenesulfonylmethyl
      isocyanide and polymer-bound imines.
AB  - A convenient method for the synthesis of 1,5-disubstituted imidazoles has been
      developed on a polymeric support using base-promoted 1,3-dipolar cycloaddition
      reaction of p-toluenesulfonylmethyl isocyanide (TOSMIC) with immobilized imines
      under microwave irradiation. The immobilized imines were synthesized by the
      reaction of various primary benzyl amines with 4-formyl-3-methoxyphenoxymethyl
      polystyrene in the presence of trimethyl orthoformate at room temperature.
      Cleavage from the polymeric support using trifluoroacetic acid gave the desired
      1,5-disubstituted imidazoles with excellent yield and high purity.

PMID- 15993062
TI  - Bicyclic nucleoside inhibitors of Varicella-Zoster virus: the effect of branching
      in the p-alkylphenyl side chain.
AB  - Further to the discovery of bicyclic furanopyrimidine nucleoside analogues
      (BCNAs) as potent anti-VZV agents, a branched series of this family of compounds
      was synthesised. The aim was to study the impact of the geometry and steric
      hindrance in the side chain as well as lipophilic role of this moiety on
      biological activity. The results showed a detrimental effect of branching on
      antiviral activity, with a different magnitude depending on the position of
      branching in the side chain. This study again showed the importance of this
      moiety for biological activity, as well as the limited efficacy of the ClogP
      value as a tool for predicting the potency of BCNAs, while suggesting an
      alternative rationale behind the design of future series.

PMID- 15993064
TI  - Radiosynthesis of carbon-11-labeled camptothecin derivatives as potential
      positron emission tomography tracers for imaging of topoisomerase I in cancers.
AB  - Four carbon-11-labeled camptothecin derivatives, 9-[11C]methoxy-20(S)
      camptothecin ([11C]5), 10-[11C]methoxy-20(S)-camptothecin ([11C]7), 9-nitro-10
      [11C]methoxy-20(S)-camptothecin ([11C]9), and 9-[([11C]trimethylamino)methyl]-10
      hydroxy-20(S)-camptothecin ([11C]11), have been synthesized as potential positron
      emission tomography tracers for imaging of topoisomerase I in cancers.

PMID- 15993063
TI  - Analysis of structure-activity relationships for the 'B-region' of N-(4-t
      butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1
      antagonists.
AB  - The structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'
      [4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1
      receptor antagonists. A docking model of potent antagonist 2 with the sensor
      region of TRPV1 is proposed.

PMID- 15993065
TI  - Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized
      antagonist side chain.
AB  - An optimized side chain for dihydrobenzoxathiin SERAMs was discovered and
      attached to four dihydrobenzoxathiin platforms. The novel SERAMs show exceptional
      estrogen antagonist activity in uterine tissue and an MCF-7 breast cancer cell
      assay.

PMID- 15993066
TI  - QSAR of adenosine A3 receptor antagonist 1,2,4-triazolo[4,3-a]quinoxalin-1-one
      derivatives using chemometric tools.
AB  - Considering the potential of selective adenosine A3 receptor subtype ligands in
      the development of prospective therapeutic agents, an attempt has been made to
      explore physicochemical requirements of 1,2,4-triazolo[4,3-a]quinoxalin-1-one
      derivatives for A3 receptor binding. In this study, lipophilicity (logP),
      physicochemical substituent constants (pi, MR, sigma p) of phenyl ring
      substituents, and Wang-Ford charges of common atoms of the quinoxaline nucleus
      (calculated from molecular electrostatic potential surface of energy-minimized
      geometry using AM1 technique) were used as independent variables along with
      suitable dummy parameters. The best multiple linear regression (MLR) equation
      obtained from factor analysis (FA-MLR) as the preprocessing step could explain
      and predict 72.6% and 65.3%, respectively, of the variance of the binding
      affinity. The same equation also emerged as the best equation in the population
      of 100 equations obtained from genetic function approximation (GFA-MLR). The
      results suggested that presence of an electron-withdrawing group at the para
      position of the phenyl ring would be favorable for the binding affinity. Again,
      the presence of a nitro group at position R1 increases the binding affinity. When
      factor scores were used as predictor variables in the principal component
      regression analysis, the resultant model showed 78.6% explained variance and
      63.1% predicted variance. The best equation derived from G/PLS could explain and
      predict 74.4% and 64.8%, respectively. The results have suggested the importance
      of Wang-Ford charges of atoms C15 and C19, apart from positive contributions of
      electron-withdrawing para substituents of the variance of the phenyl ring and
      nitro group at the R1 position.

PMID- 15993067
TI  - Determination of human serum albumin using an intramolecular charge transfer
      fluorescence probe: 4'-dimethylamino-2,5-dihydroxychalcone.
AB  - A new intramolecular charge transfer fluorescence probe, namely, 4'-dimethylamino
      2,5-dihydroxychalcone (DMADHC), exhibited dramatic enhancement of fluorescence
      intensity with an accompanying blue shift of the emission maximum when the
      concentration of human serum albumin (HSA) was increased. Binding to HSA also
      caused a progressive shift in the absorption spectrum of DMADHC, and a clear
      isosbestic point appeared. The binding site number and binding constant were
      calculated. Thermodynamic parameters were given and possible binding site was
      speculated. The optimum conditions for the determination of HSA were also
      investigated. A new, fast, and simple spectrofluorimetric method for the
      determination of HSA was developed. In the detection of HSA in samples of human
      plasma, this method gave values close to that of the Erythrosin B method.

PMID- 15993068
TI  - 2-Aminoquinazoline inhibitors of cyclin-dependent kinases.
AB  - The inhibition of cyclin-dependent kinase 4 (Cdk4) causes cell cycle arrest and
      restores a checkpoint that is absent in the majority of tumor cells. Compounds
      that inhibit Cdk4 selectively are targeted for treating cancer. Appropriate
      substitution of 2-aminoquinazolines is demonstrated to produce high levels of
      selectivity for Cdk4 versus closely related serine-threonine kinases.

PMID- 15993069
TI  - Self-assembly of bivalent protein-binding agents based on oligonucleotide-linked
      organic fragments.
AB  - A library of bidentate fragments linked through an oligonucleotide duplex was
      tested for binding to streptavidin. When one fragment was biotin, only biotin
      containing duplexes were selected by streptavidin but when heated above the
      melting temperature, only bidentate biotin ligands were obtained. Thermal
      denaturation experiments showed that the melting temperature, thus stability, of
      the monodentate versus bidentate binding ligand increased from 59 to 71 degrees C
      in the presence of streptavidin. Substituting biotin with 2-iminobiotin led to
      the exclusion of all other duplexes by the bidentate iminobiotin duplex in
      binding streptavidin.

PMID- 15993070
TI  - Chemical modification of the naphthoyl 3-position of JWH-015: in search of a
      fluorescent probe to the cannabinoid CB2 receptor.
AB  - In silico modelling was used to guide the positioning of the fluorescent dye NBD
      F on the cannabinoid CB2 receptor agonist JWH-015. While the ultimate fluorescent
      conjugate lost extensive binding affinity to the cannabinoid CB2 receptor,
      affinity and efficacy studies on the naphthoyl 3-position modified precursor
      molecules have provided new insight into structure-activity relationships
      associated with this position.

PMID- 15993071
TI  - Gas vesicles in actinomycetes: old buoys in novel habitats?
AB  - Gas vesicles are gas-filled prokaryotic organelles that function as flotation
      devices. This enables planktonic cyanobacteria and halophilic archaea to position
      themselves within the water column to make optimal use of light and nutrients.
      Few terrestrial microbes are known to contain gas vesicles. Genome sequences that
      have become available recently for many bacteria from non-planktonic habitats
      reveal gas vesicle gene clusters in members of the actinomycete genera
      Streptomyces, Frankia and Rhodococcus, which typically live in soils and
      sediments. Remarkably, there is an additional level of complexity in cluster
      number and gene content. Here, we discuss whether putative gas vesicle proteins
      in these actinomycetes might actually be involved in flotation or whether they
      might fulfil other cellular functions.

PMID- 15993072
TI  - TonB-dependent trans-envelope signalling: the exception or the rule?
AB  - TonB-dependent regulatory systems consist of six components, a specialized outer
      membrane-localized TonB-dependent receptor (TonB-dependent transducer) that
      interacts with its energizing TonB-ExbBD protein complex, a cytoplasmic membrane
      localized anti-sigma factor and an extracytoplasmic function (ECF)-subfamily
      sigma factor. This sophisticated complex senses signals from outside the
      bacterial cell and transmits them via two membranes into the cytoplasm, leading
      to transcriptional activation of target genes. TonB-dependent transducers might
      be important for pathogenicity; therefore, a survey of their presence in bacteria
      was aimed. Genome-wide analyses indicate that these systems are commonly found in
      several environmental bacteria but are only seldom present in human and animal
      pathogens. Most systems have the same tandem organization of the corresponding
      genes: sigma factor-anti-sigma factor-TonB-dependent transducer. In the course of
      these analyses, a novel protein domain of unknown function was identified and
      four different modular structures of TonB-dependent receptors were detected.

PMID- 15993073
TI  - The PIN-domain toxin-antitoxin array in mycobacteria.
AB  - PIN-domains (homologues of the pilT N-terminal domain) are small protein domains
      of approximately 140 amino acids. They are found in a diverse range of organisms
      and recent evidence from bioinformatics, biochemistry, structural biology and
      microbiology suggest that the majority of the prokaryotic PIN-domain proteins are
      the toxic components of toxin-antitoxin (TA) operons. Several microorganisms have
      a large cohort of these operons. For example, the genome of Mycobacterium
      tuberculosis encodes 48 PIN-domain proteins, of which 38 are thought to be
      involved in TA interactions. This large array of PIN-domain TA operons raises
      questions as to their evolutionary origin and contemporary functional
      significance. We suggest that the evolutionary origin of genes encoding
      mycobacterial PIN-domain TA operons is linked to the mobile gene pool, but that
      TA operons can become resident within the chromosome of host cells from where
      they might be recruited to fulfil a variety of roles associated with retardation
      of cell growth and persistence in stressful environments.

PMID- 15993074
TI  - A nutritive view on the host-pathogen interplay.
AB  - The interaction between pathogenic microbes and their host is determined by
      survival strategies on both sides, including competition for essential nutrients.
      During evolution, pathogenic microbes developed ways to access certain nutrients
      from the host, which, by contrast, can be exploited by the host for defence by
      restricting the availability of these nutrients. In this article, we review
      ecological aspects of the host-pathogen relationship and describe examples for
      competitive nutrient usage. We also discuss the beneficial probiotic microbes of
      the mammalian gut, which influence their environment including inflammatory host
      responses, and how they might be supported by prebiotic diets.

PMID- 15993075
TI  - Expression of Rac3 in human brain tumors.
AB  - Rac3 may play an important role in tumor growth but little is known about its
      expression and mutation in human tumor tissues. We examined the expression of
      Rac3 using RT-PCR and mutation of the Rac3 gene by DNA sequencing. Overexpression
      of the Rac3 gene occurred in 19% (5/26) of brain tumors; 3 of 9 (33%)
      meningiomas, 1 of 11 (9%) astrocytomas and 1 of 6 (17%) pituitary adenomas. Two
      of the 3 meningiomas with Rac3 overexpression were recurrent meningiomas. The
      only astrocytoma with Rac3 overexpression was a glioblastoma multiforme. Mutation
      of the Rac3 gene occurred in 63% (12/19) of brain tumours; 4 of 7 (57.1%)
      meningiomas, 4 of 5 (80%) pituitary adenomas and 4 of 7 (57.1%) astrocytomas.
      Except in one astrocytoma, the other four tumors with Rac3 overexpression (3
      meningiomas and one pituitary adenoma) did not have Rac3 mutations. Our data is
      the first report of the frequency of Rac3 overexpression and mutation in human
      brain tumors. Overexpression may be associated with aggressive tumor behavior.
      The relationship between Rac3 expression and mutation requires further
      investigation.

PMID- 15993076
TI  - Intraparenchymal meningioma.
AB  - A 54 year-old woman presented with severe headache. Neuroimaging showed an
      enhancing intra-axial mass in the right superior temporal region associated with
      severe peritumoral oedema. Preliminary diagnosis was cerebral metastasis. The
      mass was surgically removed. Histopathology and immunohistochemistry showed the
      mass to be an intraparenchymal meningioma, which is rare. The relevant literature
      is reviewed.

PMID- 15993077
TI  - Deep brain stimulation for pain relief: a meta-analysis.
AB  - Deep brain stimulation (DBS) has been used to treat intractable pain for over 50
      years. Variations in targets and surgical technique complicate the interpretation
      of many studies. To better understand its efficacy, we performed a meta-analysis
      of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to
      January 2003) databases were searched using key words deep brain stimulation,
      sensory thalamus, periventricular gray and pain. Inclusion criteria were based on
      patient characteristics and protocol clarity. Six studies (between 1977-1997)
      fitting the criteria were identified. Stimulation sites included the
      periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and
      sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS
      of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule
      (87%). Stimulation of the sensory thalamus alone was less effective (58% long
      term success) (p < 0.05). DBS was more effective for nociceptive than
      deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success
      was attained in over 80% of patients with intractable low back pain (failed back
      surgery) following successful trial stimulation. Trial stimulation was successful
      in approximately 50% of those with post-stroke pain, and 58% of patients
      permanently implanted achieved ongoing pain relief. Higher rates of success were
      seen with phantom limb pain and neuropathies. We conclude that DBS is frequently
      effective when used in well-selected patients. Neuroimaging and neuromodulation
      technology advances complicate the application of these results to modern
      practice. Ongoing investigations should shed further light on this complex
      clinical conundrum.

PMID- 15993078
TI  - Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8
      nitroquinazolines as EGFR signaling-targeted inhibitors.
AB  - The synthesis and biological activity of a series of novel 5-substituted-4
      hydroxy-8-nitroquinazolines that may function as inhibitors of EGFR- and/or ErbB
      2-related oncogenic signaling are described. These compounds were prepared by
      S(N)Ar reaction of 5-chloro-4-hydroxy-8-nitroquinazoline with alkyl or aryl
      amines, or alkyl alcohol as nucleophiles. Although the enzyme assay showed a weak
      inhibition effect against both EGFR and ErbB-2 tyrosine kinases, the cell-based
      antitumor activity turned out promising. Compounds having 5-anilino substituent
      exhibit high potency with 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline (1h)
      being the best dual EGFR/ErbB-2 inhibitors, which effectively inhibited the
      growth of both EGFR (MDA-MB-468, IC(50)<0.01microM) and ErbB-2 (SK-BR-3,
      IC(50)=13microM) overexpressing human tumor cell lines in vitro. More
      interestingly, the variation of the substituent(s) at the 3- and/or 4-position of
      the 5-anilino portion was found to modulate the selectivity and potency
      dramatically. However, compounds having an alkylamino or alkyloxy group at the 5
      position of 4-hydroxy-8-nitroquinazolines are essentially inactive. These results
      are consistent with molecular modeling observations. This study was the first
      attempt to identify new structural types of dual EGFR/ErbB-2-related signaling
      inhibitors by incorporation of the anilino group at the 5-position of 4-hydroxy-8
      nitroquinazolines' core structure, providing promising new templates for further
      development of potent inhibitors targeting both EGFR and ErbB-2 tyrosine kinases.

PMID- 15993079
TI  - Oligonucleotides containing 2'-O-[2-(2,3-dihydroxypropyl)amino-2-oxoethyl]uridine
      as suitable precursors of 2'-aldehyde oligonucleotides for chemoselective
      ligation.
AB  - 2'-O-[2-(2,3-Diacetoxypropyl)amino-2-oxoethyl]uridine 3'-phosphoramidite was
      prepared and used in solid-phase synthesis to obtain oligonucleotides containing
      a 1,2-diol group, which may then be converted into a 2'-aldehyde group. The
      oligonucleotides were conjugated efficiently to various molecules by
      chemoselective ligation that involves an addition-elimination reaction between
      the 2'-aldehyde group and a suitable nucleophile, such as a hydrazine, a O
      alkylhydroxylamine or an 1,2-aminothiol. The method was applied successfully to
      the conjugation of peptides to oligonucleotides at the 2'-position.

PMID- 15993080
TI  - 8-Azapurines as new inhibitors of cyclin-dependent kinases.
AB  - Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential
      anticancer drug candidate as one of the first representatives, roscovitine, is
      passing Phase II clinical trials for cancer and glomerulonephritis. In this
      article, we describe a novel modification of the purine scaffold influencing CDK2
      inhibitory activities as well as anticancer properties in cell lines of different
      histopathological origin. The introduced N at position 8 of the purine ring
      generally lowered CDK2 inhibitory activity of new 8-azapurines (1,2,3
      triazolo[4,5-d]pyrimidines) in comparison to the model trisubstituted purines,
      whereas the antiproliferative potential of some derivatives remained very high,
      reflecting their ability to activate p53 tumor suppressor.

PMID- 15993081
TI  - Hypocholesterolemic effects of phenolic-rich extracts of Chemlali olive cultivar
      in rats fed a cholesterol-rich diet.
AB  - This study was designed to test the lipid-lowering and the antioxidative
      activities of green and black olive phenolic extracts. Wistar rats fed a standard
      laboratory diet or a cholesterol-rich diet for 16 weeks were used. The serum
      lipid levels, the malondialdehyde (MDA) and the activity of superoxide dismutase
      (SOD) as well as that of catalase (CAT) were examined. The cholesterol-rich diet
      induced hypercholesterolemia that was manifested in the elevation of total
      cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). Administration
      of aqueous methanol and ethyl acetate extracts of green olives and ethyl acetate
      extract of black olives significantly lowered the serum levels of TC and LDL-C,
      while increasing the serum level of high density lipoprotein cholesterol (HDL-C).
      Furthermore, the content of MDA in liver, heart and kidney decreased
      significantly after oral administration of green and black olive extracts
      compared with those of rats fed a cholesterol-rich diet. In addition, olive
      extracts increased CAT and SOD activities in liver. These results suggested that
      the hypocholesterolemic effect of green and black olive extracts might be due to
      their abilities to lower serum cholesterol level as well as to slow down the
      lipid peroxidation process and to enhance the antioxidant enzyme activity.

PMID- 15993082
TI  - Effects of peripheral substituents on diastereoselectivity of the fifth ligand
      binding to chlorophylls, and nomenclature of the asymmetric axial coordination
      sites.
AB  - A preference for one of the two axial ligand-binding sites on the central metal
      atom of chlorophylls (Chls) and bacteriochlorophylls (BChls) was confirmed. In
      recently reported crystallographic data on PS2 and LHC2 complexes, there are 42
      Chl molecules whose fifth ligands were identified; 33 of 42 molecules bound the
      fifth ligand at the axial position where the C13(2)-methoxycarbonyl group
      protrudes (denoting as the 'back'-type isomer). Among 151 (B)Chl a/b molecules
      found in eight types of (B)Chl proteins including PS2 and LHC2, 124 molecules
      (82%) are the 'back'-type isomers. Such a statistical selection was observed not
      only for Chl a but also for Chl b and BChls a/b, indicating that the C3-, C7-,
      and C8-substituents as well as the macrocyclic pi-conjugates would have little
      influence on the ligand-binding site. Computational examinations revealed that
      the energetic gap between the 'back' and its opposite 'face' complexes was
      inherent to (B)Chls and that the C13(2)-methoxycarbonyl moiety contributed
      relatively greatly to the diastereomeric preference in the ligand binding.
      Nomenclature of the two distinguishable sides on chlorophyllous macrocycles, as
      well as the two asymmetric ligand-binding sites, is also discussed.

PMID- 15993083
TI  - 3D-QSAR analysis on benzazole derivatives as eukaryotic topoisomerase II
      inhibitors by using comparative molecular field analysis method.
AB  - Selective topoisomerase II inhibitors have created a great deal of interest in
      recent years for the design of new antitumoral compounds. 3D-QSAR analysis has
      been performed on a series of previously synthesized benzoxazole, benzimidazole,
      and oxazolo(4,5-b)pyridine derivatives, which are screened as eukaryotic
      topoisomerase II inhibitors, using comparative molecular field analysis (CoMFA)
      with partial least squares fit to predict the steric and electrostatic molecular
      field interactions for the activity. The CoMFA study was carried out using a
      training set of 16 compounds. The predictive ability of the model was assessed
      using a test set of 7 compounds. The analyzed 3D-QSAR CoMFA model has
      demonstrated a good fit, having r(2) value of 0.997 and cross-validated
      coefficient q(2) value as 0.435 for the model. The obtained model reveals that
      the electronegatively charged substituents such as NO(2) or COOCH(3) group on
      position R and/or R(1) at the heterocyclic ring system and positively charged
      atom and/or atom groups located between the benzazole moiety and 2-substituted
      phenyl ring as a bridge element improve the activity. On the other hand, a bulky
      substituent, such as methoxy group, attached to the ortho position of 2-phenyl-5
      nitro-benzoxazole (1) enhances the activity similar to compound 13, which is both
      a meta and para substituent of the phenyl group attached to the 2-position of
      benzimidazole ring system, fit into the favored steric region to improve the
      activity.

PMID- 15993084
TI  - Branched aminoglycosides: biochemical studies and antibacterial activity of
      neomycin B derivatives.
AB  - The C5''-OH group in neomycin B was glycosylated with a variety of mono- and di
      saccharides to probe the effect of introduction of additional binding elements on
      antibacterial activity and interaction with the aminoglycosides modifying enzyme
      APH(3')-IIIa. The designed structures show antibacterial activity superior to
      that of neomycin B against pathogenic and resistant strains, while in parallel
      they demonstrate poor substrate activity with APH(3')-IIIa.

PMID- 15993085
TI  - Identification of caffeoylquinic acid derivatives from Brazilian propolis as
      constituents involved in induction of granulocytic differentiation of HL-60
      cells.
AB  - We have previously reported that Brazilian propolis extracts inhibited growth of
      HL-60 human myeloid leukemia cells, which is partly attributed to the induction
      of apoptosis associated with granulocytic differentiation. In this study, we
      isolated three compounds which induce granulocytic differentiation evaluated by
      nitroblue tetrazolium (NBT)-reducing assays from the water extract of propolis
      and identified as 4,5-di-O-caffeoylquinic, 3,5-di-O-caffeoylquinic, and 3,4-di-O
      caffeoylquinic acids by NMR analysis. Cell growth inhibitory activity of these
      caffeoylquinic acids was found in HL-60 cell, which was mainly attributed to the
      induction of apoptosis. Furthermore, the potency of caffeoylquinic acid
      derivatives to induce granulocytic differentiation was examined in HL-60 cells.
      Caffeic, quinic, and chlorogenic acids had no effects on the NBT-reducing
      activity, while 3,4,5-tri-O-caffeoylquinic acid induced more than 30% of NBT
      positive cells. These results suggest that the number of the caffeoyl groups
      bound to quinic acid plays an important role in the potency of the caffeoylquinic
      acid derivatives to induce granulocytic differentiation. This is the first report
      demonstrating that the caffeoylquinic acid derivatives induce granulocytic
      differentiation of HL-60 cells.

PMID- 15993086
TI  - Design, synthesis, and evaluation of novel 2-substituted-4-aryl-6,7,8,9
      tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-ones as NK1 antagonists.
AB  - A series of novel bicyclic pyrimidine derivatives was prepared as part of a
      search for NK1 antagonist aimed at the treatment of urinary incontinence. Among
      them, 3g, a pyrimido[4,5-b][1,5]oxazocine derivative, bearing a 4
      acetylpiperazinyl group and a 2-methylphenyl group, was shown to have potent NK1
      antagonist activity with a K(B) value of 0.105 nM and markedly increased the
      effective bladder capacity of guinea pigs (59.4% at 0.3 mg/kg iv and 62.8% at 3
      mg/kg id). Furthermore, the effect of 3g on bladder function appeared to differ
      from that of tolterodine, another classical anti-pollakiuria agent, as determined
      by the distention-induced rhythmic bladder contraction assay using a urethane
      anesthetized guinea pig model. Compound 3g is expected to be a promising agent
      for the treatment of urinary incontinence.

PMID- 15993087
TI  - Protein oligomerization: how and why.
AB  - A large fraction of cellular proteins are oligomeric. Protein oligomerization may
      often be an advantageous feature from the perspective of protein evolution and
      has probably evolved by a variety of mechanisms. The study of protein
      oligomerization may provide insights into the early protein environment and the
      evolution of modern proteins. Oligomeric mini-proteins, short peptides with
      discrete protein-like structures, may serve as valuable models for understanding
      features of protein oligomerization.

PMID- 15993088
TI  - Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin
      transporter. Part 4: 3-Alkyl-4-halo-6-nitroquipazines.
AB  - On the basis of the structure-activity relationship (SAR) of 4-chloro-6
      nitroquipazine (Ki = 0.03 nM) and 3-fluoropropyl-6-nitroquipazine (Ki = 0.32 nM),
      3-alkyl-4-halo-6-nitroquipazines were synthesized and tested for their potential
      abilities in vitro to displace [3H]citalopram binding to the rat cortical
      membranes. Binding affinities of 3b and 4d were Ki = 2.70+/-0.32 and 2.23+/-0.46
      nM, respectively. The syntheses of 3-alkyl-4-halo-6-nitroquipazine, their in
      vitro binding affinities, and the SAR of C3, C4 position in 6-nitroquipazine are
      described.

PMID- 15993089
TI  - Novel 3-amino-2-hydroxy acids containing protease inhibitors. Part 1: Synthesis
      and kinetic characterization as aminopeptidase P inhibitors.
AB  - Novel, potent inhibitors of aminopeptidase P, containing a 3-amino-2-hydroxy acid
      and a proline or a proline analogues, have been prepared. One part of the
      bestatin-derived inhibitors was found to inhibit APP from Escherichia coli and
      from rat intestine according to a mixed-type mechanism, with Ki values up to 1.26
      microM. The other compounds, 3-amino-2-hydroxy acyl prolines of a different
      configuration, inhibit APP competitively, according to a slow-binding mechanism,
      with Ki values in the nanomolar up to the micromolar range.

PMID- 15993090
TI  - Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their
      structure-anti-mycobacterial activities.
AB  - The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer
      aided study of their in vitro anti-tubercular activity against Mycobacterium
      tuberculosis H37Rv (ATCC 27294) are reported. The average accuracy of the
      electronic-topological method and neural network methods applied to the activity
      prediction in leave-one-out cross validation is 80%.

PMID- 15993091
TI  - Lewis acid-promoted transformation of 2-alkoxypyridines into 2-aminopyridines and
      their antibacterial activity. Part 2: Remarkably facile C-N bond formation.
AB  - 2-Alkoxy-3-cyano-4,6-diarylpyridines 1a,b which were synthesized by condensation
      of alpha,beta-unsaturated ketones with malononitrils were subjected to Lewis acid
      catalyzed nucleophilic displacement reaction with various amines to afford the
      corresponding 2-aminopyridines 3-21. The potency of the results as antibacterial
      agents has been evaluated. The structure of the newly prepared compounds was
      assessed by microanalysis, IR, and NMR spectra. Molecular modeling and QSAR
      methods are used to study the antibacterial activity of the active compounds by
      means of the molecular mechanic method.

PMID- 15993092
TI  - Ginkgolides and bilobalide: their physical, chromatographic and spectroscopic
      properties.
AB  - Ginkgolides A, B, C, J, K, L and M and bilobalide are rare terpene trilactones
      that have been isolated from leaves and root bark of the Chinese tree Ginkgo
      biloba. The structures of the highly oxidized ginkgolides were independently
      elucidated in the 1960s by the groups of Nakanishi and Sakabe. Later these
      compounds were found to be potent and selective antagonists of platelet
      activating factor, which fact triggered much new research. During the past 40
      years, much physical, chromatographic and spectroscopic data have been published
      on these compounds in various, sometimes inaccessible, sources. The published
      melting points, solubility in different solvents, ionization constants,
      chromatographic behaviour, specific optical rotations, UV, IR, MS and NMR data,
      and X-ray studies are summarized and, where necessary, discussed. The literature
      until April 2005 has been reviewed.

PMID- 15993093
TI  - Imaging amyloid beta peptide oligomeric particles in solution.
AB  - While all protein misfolding diseases are characterized by fibrous amyloid
      deposits, the favorable free energy and strongly cooperative nature of the self
      assembly have complicated the development of therapeutic strategies aimed at
      preventing their formation. As structural models for the amyloid fibrils approach
      atomic resolution, increasing evidence suggests that early folding intermediates,
      rather than the final structure, are more strongly associated with the loss of
      neuronal function. For that reason we now demonstrate the use of cryo-etch high
      resolution scanning electron microscopy (cryo-HRSEM) for the direct observation
      of pathway intermediates in amyloid assembly. A congener of the Abeta peptide of
      Alzheimer's disease, Abeta(13-21), samples a variety of time-dependent self
      assembles in a manner similar to those seen for larger proteins. A morphological
      description of these intermediates is the first step towards their structural
      characterization and the definition of their role in both amyloid assembly and
      neurotoxicity.

PMID- 15993094
TI  - A novel and selective monoamine oxidase B substrate.
AB  - Cyclic five- and six-membered tertiary allylamines constitute a unique class of
      monoamine oxidase substrates that undergo a net two-electron alpha-carbon
      oxidation to form the cyclic, conjugated eniminium metabolites. The corresponding
      saturated pyrrolidinyl and piperidinyl systems are not substrates for this
      flavoenzyme system. In an attempt to evaluate possible contributions that pi
      orbital stabilization of the putative alpha-carbon radical intermediates may play
      in the catalytic pathway, we have examined the substrate properties of 3-methyl-6
      phenyl-3-aza-bicyclo[4.1.0]heptane, the 3,4-cyclopropyl analog of the selective
      monoamine oxidase B substrate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). The results, which document the first reported example of a saturated,
      cyclic tertiary amine with monoamine oxidase substrate properties, are consistent
      with alpha-carbon radical stabilization as a contributing factor in the catalytic
      pathway.

PMID- 15993095
TI  - Higher NORs-expression in lymphocyte of trisomy 21 babies/children: in vivo
      evaluation.
AB  - Extra chromosome 21 of Down syndrome (DS) or trisomy 21 patients contains an
      average of 40 extra copies of rRNA genes and the in vivo regulation of these
      genes is not known. The objective of this work is to compare the NORs expression
      in interphase nuclei in non-stimulated lymphocytes of DS patients and healthy
      controls. Because the AgNOR staining is the indicator of the active rRNA genes,
      comparison of the image analysis values of AgNORs area between DS's and healthy
      controls' interphase lymphocytes is considered to be sufficient to evaluate the
      level of rDNA activities in the two groups. The Nucleolus Organizer Regions
      area/Total Nuclear area (NORa/TNa) was calculated using a computer program
      designed by us. 100 consecutive NORa/TNa per individual were evaluated. We report
      that 24 DS children's peripheral lymphocytes show significantly higher NORa/TNa
      mean value (6.32 +/- 1.77%) than that of the 20 healthy controls' cells (5.31 +/-
      1.34%) (2-tailed Mann-Whitney U test, z = 19.4, P = 0.000). The same is true for
      the nucleolus (AgNOR spot) number per nucleus. The mean value of nucleoli number
      per nucleus in DS lymphocytes was significantly higher than that of the controls:
      z = 14.6, P = 0.000. In conclusion, extra rRNA genes on the chromosome 21 are not
      down-regulated in DS patients' lymphocytes. Rather, extra NORs expressions in 'in
      vivo' condition contribute to the increase of AgNORs area and AgNOR spots number
      per nucleus. This is the first work on the comparison of NORs activities in
      resting (non-stimulated) interphase lymphocytes between DS and healthy controls.

PMID- 15993096
TI  - On the physical transformations of processed pharmaceutical solids.
AB  - Atomic force microscopy Phase Imaging, an adaptation of Tapping Mode AFM was used
      to visualise physico-mechanical variations on the surface of crystalline
      materials after being subjected to mechanically induced lattice damage. Large
      crystals (100-500 microm) of lactose were nucleated on AFM sample stubs, imaged
      and subjected to a milling process. The milled samples were then imaged at
      specific humidity using Phase Imaging. Phase and Amplitude images of the re
      crystallised lactose suggested an ordered crystalline state with multiple
      platelets present across the surface. In comparison, the morphology and surface
      properties after a 1-min mill time suggested milling had a dramatic effect on the
      surface characteristics of the re-crystallised lactose. Phase and Topographical
      imaging during exposure to elevated humidities (70% RH) indicated both
      morphological and physico-mechanical changes that may be linked to surface
      amorphous re-crystallisation.

PMID- 15993097
TI  - TNF-alpha activates death pathway in human aorta smooth muscle cell in the
      presence of 7-ketocholesterol.
AB  - This study was undertaken to investigate whether a physiologically compatible
      concentration of 7-ketocholesterol had any effect on human vascular smooth muscle
      cells (HVSMCs). We found that 7-ketocholesterol changed the viability of human
      aorta smooth muscle cells (HAoSMC) not by cytotoxicity but by activation of tumor
      necrosis factor-alpha receptor (TNFR)-mediated death. Whereas TNF-alpha did not
      affect the viability in the presence of 7alpha-hydroxycholesterol or cholesterol,
      the cytokine induced HAoSMC death in the presence of 7-ketocholesterol as
      detected by morphology, viability, and fragmentation of chromosomal DNA. The
      HAoSMC death was inhibited by a neutralizing anti-TNF receptor 1 (TNFR1) antibody
      and by the caspase inhibitors of z-VAD and z-DEVD. Activations of caspase-8 and 
      3 were detected from dying HAoSMCs. 7-Ketocholesterol inhibited translocation of
      the nuclear factor kappaB (NF-kappaB) subunits of p65 and p50 from the cytosol
      into the nucleus, increase of NF-kappaB activity, and expression of caspase-8
      homolog Fas ligand interleukin-1-converting enzyme inhibitory protein by TNF
      alpha. We also found that X-chromosome-linked inhibitor of apoptosis protein was
      degraded in dying HAoSMC. The present study proposes that 7-ketocholesterol would
      contribute to the disappearance of HVSMC in the atherosclerotic lesions by
      enhancing receptor-mediated death. This is the first report demonstrating
      induction of TNF-alpha-mediated death by oxysterol in cells.

PMID- 15993098
TI  - Osteopontin is upregulated by BCR-ABL.
AB  - Chronic myelogenous leukemia (CML) is characterized by its hallmark oncogene BCR
      ABL and the progression from a chronic phase toward an acute leukemia, with a
      differentiation arrest of the leukemic clone. In the present study, we conducted
      a microarray analysis using an inducible model of BCR-ABL expression based on the
      TET-OFF system, and we found that osteopontin (OPN), a component of stem cell
      niche, is overexpressed in BCR-ABL-expressing cells. Studies using mutant forms
      of BCR-ABL demonstrated that the BCR-ABL-induced OPN overexpression was a
      tyrosine kinase-dependent event. Furthermore, OPN concentration was significantly
      increased in the serum of leukemic mice generated by transplantation of BCR-ABL
      expressing bone marrow cells. Most importantly, a significant increase of OPN
      concentration was observed in the serum of CML patients as compared to controls.
      Overall these results show that OPN is deregulated by BCR-ABL oncogene and
      suggest that OPN could be involved in CML stem cell biology.

PMID- 15993099
TI  - The dioxin-like PCB 77 but not the ortho-substituted PCB 153 interferes with
      chicken embryo thyroid hormone homeostasis and delays hatching.
AB  - The effects of the dioxin-like polychlorinated biphenyl (PCB) 77 and the ortho
      substituted PCB 153 on thyroid hormone availability were investigated during the
      last week of embryonic development in chicken. High doses of these PCBs (1microg
      PCB 77 and 20microg PCB 153) were injected into chicken eggs at day 4 of
      incubation. Blood and tissue samples were collected from day 14 of incubation
      until 1 day after hatching. We did not observe influences of PCB 153 on thyroid
      hormone (TH) levels. Treatment with PCB 77, on the other hand, decreased plasma
      total T(4) concentrations but increased hepatic T(4) levels at day 14 of
      incubation. Later in development, at stages near the process of hatching, severe
      decreases of T(4) and T(3) levels were observed in the PCB 77 group, both in
      plasma and tissues. PCB 77 severely reduced the TH peak that normally coincides
      with the stage of internal pipping. This reduction was accompanied by a
      considerable delay in the moment of hatching. We conclude that the dioxin-like
      PCB 77, but not the ortho-substituted PCB 153, can decrease TH availability
      towards the end of embryonic development and hence disturb the process of
      hatching.

PMID- 15993100
TI  - Characterization of adrenomedullin in birds.
AB  - Adrenomedullin (AM) is a multifunctional evolutionarily highly conserved peptide.
      Although its genomic and amino acid (aa) sequences are known in several mammalian
      species and in fish, the structure of the AM gene remains unknown in intermediate
      phyla, including birds. Here, we report the structure and aa sequence of the
      chicken (c) AM ortholog. The cAM gene is located at the short arm of chromosome
      5, which shows high synteny with the short arm of human (h) chromosome 11, where
      hAM is located. Key sequences in the third intron have been conserved which allow
      for an alternative splicing mechanism, similar to the one found in mammals. The
      preprohormone contains two peptides with high homology to human proadrenomedullin
      N-terminal 20 peptide (PAMP) and hAM. We found through real-time PCR and
      immunocytochemistry cAM mRNA and peptide expression in a variety of chicken
      tissues, which parallel patterns observed for mammals, with the exception that
      cAM levels are almost non-detectable in brain. Similarly to mammals, cAM
      expression is upregulated under hypoxic conditions and following dexamethasone
      treatment. These data demonstrate a high degree of homology between the cAM gene
      and its mammalian ortholog and evolutionary conservation of the regulatory
      mechanisms controlling its expression.

PMID- 15993101
TI  - Brain aromatase from pejerrey fish (Odontesthes bonariensis): cDNA cloning,
      tissue expression, and immunohistochemical localization.
AB  - The brain-type aromatase (CYP19A2) cDNA from pejerrey Odontesthes bonariensis was
      characterized. Its sequence differs from the ovarian-derived aromatase (CYP19A1)
      previously reported for the same species. The cDNA is 2305bp in length and the
      deduced protein comprises 501 amino-acids. The percentage of identity was higher
      when compared to other brain-derived aromatase proteins (85-63%) and lower with
      ovarian-derived aromatases (64-57%). Pejerrey aromatases share 61% of identity.
      The tissue expression analysis showed that CYP19A2 was expressed in the kidney,
      brain, and pituitary gland of both sexes and also in the ovary, but not in the
      eye, spleen, liver, gill, and testis. Semi-quantitative RT-PCR analysis of
      different brain areas revealed that CYP19A2 was expressed significantly higher in
      anterior male brain areas than in the corresponding female areas, and also when
      compared to posterior brain areas from both sexes. An immunological analysis
      using a polyclonal anti-teleost aromatase showed immunoreactive aromatase cells
      bordering the telencephalic ventricle and a strong signal in the ependymal cells
      of the preoptic area and the hypothalamus. In the optic tectum immunoreactive
      aromatase cells were labeled in the ventral wall and in the ependymal layer of
      the third and fourth ventricle with lateral projections. In the pituitary gland
      immunoreactive aromatase cells could be found in the rostral and proximal pars
      distalis. In this gland, aromatase fibers were also detected in different areas;
      many of them concentrated around blood vessels.

PMID- 15993102
TI  - Season- and age-related variation in neural cGnRH-I and cGnRH-II immunoreactivity
      in house sparrows (Passer domesticus).
AB  - Vertebrates exhibit several forms of gonadotropin-releasing hormone (GnRH). In
      birds, chicken GnRH-I (cGnRH-I) is the primary hypophysiotropic form that
      regulates the hypothalamo-pituitary-gonad (HPG) axis. In seasonally breeding
      songbirds, cGnRH-I immunoreactivity is primarily in the preoptic septo
      infidibular regions and varies greatly between the breeding and non-breeding
      season. Chicken GnRH-II (cGnRH-II) is more widely distributed throughout the
      avian brain, but cGnRH-II immunoreactivity has been found in the median eminence
      of quail. Thus, cGnRH-II may function in addition to cGnRH-I in the regulation of
      the HPG axis. If so, we predicted that cGnRH-II immunoreactivity should exhibit
      seasonal and age related variation similar to that observed for cGnRH-I. In this
      study, we compared hypothalamic immunoreactivity of cGnRH-I and -II (ir-cGnRH-I
      and ir-cGnRH-II) between breeding and non-breeding adult and juvenile house
      sparrows (Passer domesticus). We used immunocytochemistry with highly specific
      antibodies developed for quail to examine brains of free-living house sparrows
      collected in the breeding and non-breeding season. Results showed a greater
      number of ir-cGnRH-I cell bodies and beaded fibres in breeding adult birds
      compared to non-breeding adult and juvenile birds. Moreover, there were
      significantly more ir-cGnRH-II fibres in the preoptic area of breeding adult
      birds compared to non-breeding adult and juvenile birds. These data suggest that
      cGnRH-II undergoes seasonal- and age-related changes similar to cGnRH-I and
      implicate a role in regulating reproduction.

PMID- 15993103
TI  - No evidence of androgenic hormone from the testes of the glowworm, Lampyris
      noctiluca.
AB  - The widely accepted concept, stating that insects have no true sex hormones, and
      that primary as well as secondary sex characteristics are controlled by the
      genetic inventory of each single cell, is challenged by the report of Naisse, J.
      [1966a. Controle endocrinien de la differenciation sexuelle chez l'Insecte
      Lampyris noctiluca (Coleoptere Malacoderme Lampyride). I. Role androgene des
      testicules, Arch. Biol. Liege, 77, 139-201] on the discovery of an androgenic
      hormone in the glowworm, Lampyris noctiluca. This case is of special interest,
      since it may point to an ancestral mode of sex differentiation in arthropods,
      considering that androgenic hormones have been discovered and characterized in
      crustaceans. With the intention to further characterize the androgenic hormone in
      the glowworm, and to establish a bioassay, we tried to repeat Naisses's
      transplantation experiments, according to which, androgen producing testes
      implanted into female larvae should masculinize the female's gonads and all other
      female features of the sexually strongly dimorphic pupae and beetles. We found,
      however, that larval development of the glowworm proceeded differently than
      reported by Naisse, and that sexing of larvae was not possible. Therefore,
      "blind" transplantations had to be performed. The results of our experiments
      showed, however, unequivocally, that an androgenic hormone, allegedly synthesized
      by the apical tissue of larval testes, was not involved in sex differentiation.
      We found, that in transplants, where testes and ovaries were even located closely
      to each other, both matured and formed spermatozoa in the testes and vitellogenic
      oocytes in the ovaries. Masculinization of ovaries was never observed, and the
      sex of the recipient was always in accordance with the sex of its own gonads. We
      therefore conclude that Lampyris noctiluca does not synthesize an androgenic
      hormone in the larval testes, and that sex differentiation is probably regulated
      as in other insect species. (The apical testis tissue of the glowworm was
      previously shown to represent progenitors of spermatogonial cyst cells [Balles,
      S., Maas, U., Sehn, E., Dorn, A., 2002. Testis differentiation in the glowworm,
      Lampyris noctiluca, with special reference to the apical tissue. J. Morphol. 251,
      22-37].).

PMID- 15993104
TI  - Gonadal steroids vary with reproductive stage in a tropically breeding female
      anuran.
AB  - Tropically breeding anurans that require heavy rainfall in order to reproduce are
      subject to favorable breeding conditions that are sporadic. Although there is an
      increased probability of rain during the rainy season, the probability of local
      rainfall is unpredictable and this may influence female anuran reproductive
      strategies. The female tungara frog, a neotropical frog that requires standing
      water to breed, maintains readiness to breed at any time via asynchronous
      oogenesis. Although females constantly produce and maintain oocytes during the
      breeding season, this study shows that they have cyclic fluctuations in gonadal
      hormone levels. Plasma levels of estrogen significantly change during three
      reproductive stages within a single reproductive cycle (P=0.03), as do plasma
      levels of progesterone and androgen (P<0.001 and P=0.001, respectively).
      Furthermore, elevation in plasma estrogen and progesterone concentrations occurs
      during the same reproductive stage in which it has been reported that females
      display the maximum frequency of reproductive behaviors, the amplexed stage.
      Androgen levels, however, are elevated prior to the reproductive stage in which
      females display maximal reproductive behavior, that is, the unamplexed stage. Our
      study suggests that the pattern of gonadal hormone fluctuation in a tropically
      breeding female anuran is similar to the classic paradigm in which there is a
      temporal relationship between the appearance of reproductive hormones and
      reproductive behaviors.

PMID- 15993105
TI  - Production and characterisation of gilthead sea bream (Sparus auratus)
      recombinant parathyroid hormone related protein.
AB  - The production and purification of gilthead sea bream recombinant parathyroid
      hormone related protein [sbPTHrP(1-125)] using an Escherichia coli system and one
      step purification process with continuous elution gel electrophoresis is
      reported. The cDNA encoding sbPTHrP(1-125) was cloned into a prokaryotic
      expression vector pET-11a. The recombinant plasmid was used to transfect E. coli
      BL21(DE3) pLysS and sbPTHrP(1-125) synthesis was induced by addition of 1mM
      isopropyl-beta-d-thiogalactopyranoside. The rapid one step isolation method gave
      pure sbPTHrP(1-125) as judged by SDS-PAGE and yielded up to 40mg/L of culture
      medium (3.3mg protein/g of bacteria). The bioactivity of recombinant sbPTHrP(1
      125) assessed using an in vitro scale bioassay was found to be equipotent to
      PTHrP(1-34) in stimulating cAMP accumulation. Assessment of the immunological
      reactivity of the isolated protein by Western blot revealed it cross-reacts with
      antisera specific for the N-terminal and C-terminal region of PTHrP. In a
      radioimmunoassay specific for piscine N-terminal (1-34aa) PTHrP, the recombinant
      sbPTHrP(1-125) was equipotent with PTHrP(1-34) in displacing labelled (125)I
      PTHrP(1-36) PTHrP from the antisera. The availability of recombinant sbPTHrP will
      allow the development of region specific assays and studies aimed at defining
      post-secretory processing of this protein and its biological activity in fish.

PMID- 15993106
TI  - Hypocorticism and interrenal hyperplasia are not directly related to
      masculinization in XX mas(-1)/mas(-1) carp, Cyprinus carpio.
AB  - This study reports on a homozygous XX male strain of common carp (E5), which fail
      to mount a normal cortisol stress response. Earlier classical genetic analysis
      had indicated that masculinization of E5 fish was caused by a putative recessive
      mutation (mas(-1)/mas(-1)). Hypocorticism in E5 fish was studied to investigate
      if it was related to masculinization. Head-kidney tissues isolated from E5 fish
      showed a low cortisol-producing capacity in vitro, and also demonstrated a
      reduced sensitivity to stimulation with ACTH, when compared with an isogenic XY
      male carp strain (STD). There was no strain difference in androgen production by
      head-kidney tissues in vitro. E5 fish exhibited significant hyperplasia of the
      interrenal tissue (adrenal homologue of teleost fish) located in the head-kidney.
      Conversion of pregnenolone was significantly lower in E5 head-kidney homogenates,
      compared to STD homogenates, however, no strain difference was found in the
      conversion of 17alpha-hydroxyprogesterone into cortisol. Gonad homogenates
      incubated with pregnenolone showed no strain difference in conversion to
      corticosteroids and androgens. Results indicate that the interrenal hyperplasia
      and hypocorticism in this strain of carp may be due to a dysfunction of the
      17alpha-hydroxylase activity of the enzyme P450c17 in the interrenal, but that
      this defect may not be the primary factor resulting in masculinization of these
      XX genotypes.

PMID- 15993107
TI  - Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl
      Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain
      type II deiodinase.
AB  - In the present study, morphological changes leading to complete metamorphosis
      have been induced in the neotenic axolotl Ambystoma mexicanum using a
      submetamorphic dose of T(4) together with an injection of corticotropin-releasing
      hormone (CRH). An injection of CRH alone is ineffective in this regard presumably
      due to a lack of thyrotropic stimulation. Using this low hormone profile for
      induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be
      present in amphibians were measured in liver and brain 24h following an
      intraperitoneal injection. An injection of T(4) alone did not influence liver nor
      brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4)
      decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher
      dose of DEX, though CRH did not have this effect. A profound synergistic effect
      occurred when T(4) and DEX or CRH were injected together, in the dose range
      leading to metamorphosis, increasing brain D2 activity more than fivefold. This
      synergistic effect was not found in the liver. It is concluded that brain T(3)
      availability may play an important role for the onset of metamorphosis in the
      neotenic axolotl.

PMID- 15993108
TI  - Characterization and immunohistochemical visualization of the vasotocin VT2
      receptor in the pituitary gland of the chicken, Gallus gallus.
AB  - Arginine vasotocin is a neurohypophysial hormone in lower vertebrates including
      birds. Its actions are mediated through G-protein coupled receptors that belong
      to the vasopressin/oxytocin receptor family. Our laboratory recently cloned a
      vasotocin receptor, designated the VT2 receptor (VT2R), which shares high
      sequence identity at both the nucleotide and amino acid level with the mammalian
      V1b vasopressin receptor (V1bR). In the present study, we report development and
      use of an antibody to the VT2R to obtain anatomical evidence for testing the
      hypothesis that the VT2R is the avian homolog of the mammalian V1bR. Results
      verified the specificity of the antibody and demonstrated a receptor distribution
      occurring predominantly in the cephalic lobe of the pars distalis and co
      localizing with adrenocorticotropin in corticotrophs. With respect to VT2R
      distribution and cell-type localization in pituitary gland, evidence presented
      support its similarity with the mammalian V1bR. In contrast to the mammalian
      V1bR, VT2R expression was not observed in chicken brain. Further research will be
      required to determine which receptor/s in the arginine vasotocin/mesotocin family
      are expressed in brain and mediate regulatory functions of vasotocin in the
      central nervous system.

PMID- 15993109
TI  - Cloning and characterization of the gene encoding growth hormone in finback whale
      (Balaenoptera physalus).
AB  - In mammals growth hormone (GH) is generally a strongly conserved protein,
      reflecting a slow rate of molecular evolution. However, during primate and
      artiodactyl evolution episodes of rapid change occurred, so that the GHs of
      higher primates and ruminants differ markedly from those of other mammals. To
      extend knowledge of GH evolution in Cetartiodactyla (Artiodactyla plus Cetacea)
      we have previously characterized GH genes from several members of this group,
      including the common dolphin. Surprisingly the sequence deduced for dolphin GH
      differed at several residues from that described previously for another cetacean,
      finback whale. To investigate this anomaly we have now cloned and characterized
      the GH gene from finback whale. The overall organization of this gene is similar
      to that of dolphin, and the deduced amino acid sequence of finback whale GH
      differs from that of dolphin GH at only residue 47, and from that of pig GH at
      only residue 149. Phylogenetic analysis of the data provides further support for
      inclusion of Cetacea within the order Cetartiodactyla, as sister group of
      Hippopotamidae. The results support the idea that in Cetartiodactyla a burst of
      rapid evolution of GH occurred after the separation of the line leading to
      ruminants from other cetartiodactyls. Overall, the GH gene in cetaceans appears
      to be evolving more slowly than in most other cetartiodactyls.

PMID- 15993111
TI  - Pediatric spine injuries.
AB  - Pediatric spine injuries are rare, not only due to the plasticity of the
      pediatric spine, but also due to the difficulty of diagnosis and the usually
      severe, if not fatal, associated injuries. Mechanisms of injury, transportation,
      initial management, diagnostic exams, and management of such lesions are
      different from those of the adult, and an individualized approach to each case,
      looking for specific injury patterns, avoids misdiagnosis. The goal of this
      manuscripts is to summarize the specific spinal injury patterns of the pediatric
      population, as well as the present literature regarding their diagnosis and
      treatment.

PMID- 15993112
TI  - Current status of clinical trials for acute spinal cord injury.
AB  - Acute spinal cord injury (ASCI) occurs as a result of physical disruption of
      spinal cord axons through the epicenter of injury leading to deficits in motor,
      sensory, and autonomic function. This is a debilitating neurological disorder
      common in young adults that often requires life-long therapy and rehabilitative
      care, placing a significant burden on our healthcare system. While no cure
      exists, research has identified various pharmacological compounds that
      specifically antagonize primary and secondary mechanisms contributing to the
      etiology of ASCI. Several compounds including methylprednisolone (MPSS), GM-1
      ganglio-side, thyrotropin releasing hormone (TRH), nimodipine, and gacyclidine
      have been tested in prospective randomized clinical trials of ASCI. MPSS and GM-1
      ganglioside have shown evidence of modest benefits. Clearly trials of improved
      neuroprotective agents are required. Promising potential therapies for ASCI
      include riluzole, minocycline, erythropoietin, and the fusogen polyethylene
      glycol, as well as mild hypothermia.

PMID- 15993113
TI  - The role and timing of early decompression for cervical spinal cord injury:
      update with a review of recent clinical evidence.
AB  - It remains controversial whether early decompression following spinal cord injury
      conveys a benefit in neurological outcome. The goal of this paper is to provide
      evidence-based recommendations regarding spinal cord decompression in patients
      with acute spinal cord injury. We performed a Medline search of experimental and
      clinical studies reporting on the effect of decompression on neurological outcome
      following spinal cord injury. Animal studies consistently show that neurological
      recovery is enhanced by early decompression. One randomized controlled trial
      showed no benefit to early (<72 h) decompression, however, several recent
      prospective series suggest that early decompression (<12 h) can be performed
      safely and may improve neurological outcomes. A recent meta-analysis showed that
      early decompression (<24 h) resulted in statistically better outcomes compared to
      both delayed decompression and conservative management. Currently, there are no
      standards regarding the role and timing of decompression in acute spinal cord
      injury. We recommend urgent decompression of bilateral locked facets in patients
      with incomplete tetraplegia or in patients with spinal cord injury experiencing
      neurological deterioration. Urgent decompression in acute cervical spinal cord
      injury remains a reasonable practice option and can be performed safely.

PMID- 15993114
TI  - Approach and considerations regarding the patient with spinal injury.
AB  - Spinal trauma often results in a complex interaction of injuries to the
      musculoskeletal and nervous systems. This combination of biomechanical and
      neurological considerations provides a unique challenge to those dealing with the
      spinally injured patient. Proper assessment of the injuries sustained by the
      patient remains the initial, yet key, step in determining appropriate management.
      The aim of the physical examination is not only to characterize the nature of the
      injury to the vertebral column, but also to determine the extent of actual and
      potential damage to the neural elements. It is also concerned with detecting
      associated injuries of the brain, viscera, and limbs that can impact on
      management and outcome, particularly of any neurological deficit. Further
      information about the spinal column and spinal cord is derived from appropriate
      radiological assessment, which is evolving with the increasing sophistication of
      imaging modalities. In spinal injury, classification systems are particularly
      important as they simplify a diverse range of injury patterns into a useable and
      reproducible form that may be used to aid communication among clinicians, guide
      management for individual patients, and provide the basis for research
      consistency. The medical management involves consideration of the impact of
      spinal injury, in particular cord injury, on aspects including resuscitation and
      anticoagulation, as well as the role of steroids. The definitive management of
      the spinal column injury may be operative or nonoperative. Factors influencing
      this decision are biomechanical (stabilization of the unstable spine and
      reduction of deformity) and neurological (improvement in deficit and
      decompression of neural elements). This article considers these issues and aims
      to present a balanced and useful algorithm for clinicians to use when faced with
      spinal injury.

PMID- 15993115
TI  - Treatment of traumatic cervical spine instability with interbody fusion cages: a
      prospective controlled study with a 2-year follow-up.
AB  - INTRODUCTION: The purpose of this prospective cohort study was to define
      indications and analyze the clinical and radiographic results of using interbody
      cages to surgically treat traumatic cervical spine instability. PATIENTS AND
      METHODS: 53 patients were treated by monosegmental anterior discectomy and
      interbody fusion using either autologous tricortical iliac crest bone graft and
      CSLP (cervical spine locking plate) (bone graft group, n=26) or Syncage-C filled
      with autologous cancellous bone grafts and CSLP (cage group n=27). Indications
      for surgery were traumatic cervical spine instability classified according to the
      AO classification as B1, B2, B3, C2, or C3. Intraoperative parameters such as
      blood loss and operation time were assessed. Prior to surgery and at follow-up
      (6,12, and 24 months), evaluation included measurement of neck pain, shoulder/arm
      pain, muscle strength, Neck Pain Disability Index (NPDI), and Cervical Spine
      Functional Score (CSFS). Neurological and overall outcome was assessed using the
      ASIA impairment scale and Odom's criteria, respectively. In addition,
      radiographic evaluation, including plain x-rays, flexion-extension views, and CT
      scans was performed. Fusion, segmental mobility, segmental lordosis/kyphosis and
      disc space height were determined. RESULTS: Operation time and hospital stay were
      significantly shorter (p<0.05) in the cage group than in the bone graft group.
      After 6,12, and 24 months there was no difference between either group in pain,
      muscle strength, NPDI, CSFS, neurological and overall outcome. Although the cage
      group showed a trend for prolonged fusion process, there was no statistically
      significant difference between the groups for all radiographic parameters.
      CONCLUSION: Under strict indications, cages offer a valid alternative to a
      tricortical iliac crest bone graft in the surgical treatment of monosegmental
      traumatic cervical spine instability. Although there was no significant
      difference between the cage and the bone graft group in the functional and
      radiographic outcome, less donor site morbidity, a shorter operating time, and a
      reduced hospital stay might result in cost-effectiveness of cages.

PMID- 15993116
TI  - Posterior stabilization of subaxial cervical spine trauma: indications and
      techniques.
AB  - The use of instrumentation for stabilization following cervical trauma has
      evolved rapidly in the past few decades. Nonoperative maneuvers, including
      traction, extended bed rest, and cast immobilization, have given way to wiring or
      screw rod constructs that allow immediate fixation and early mobilization of the
      patient. These procedures can be performed soon after trauma and with a minimum
      of surgical risk. They offer immediate stability of the injured spine, and can
      prevent the sequelae of acute cervical spinal cord injury that may accompany
      prolonged bed rest, thus allowing early rehabilitation and the potential for
      improved recovery. Current techniques for posterior cervical spine stabilization
      following trauma include spinous process or facet wiring [1-9], lateral mass
      plating [10-18], and cervical pedicle screws [19-27]. Several radiological tools,
      including MRI [28] and reformatted CT, yield precise details of the injured spine
      and allow the treating physician to determine which, if any, fixation technique
      offers the best chance of recovery with the least amount of risk. The goals of
      surgery following acute cervical spine injury include decompressing the injured
      spinal cord or nerve root, maintaining alignment, providing stability to the
      spine, promoting healing and fusion, and allowing early mobilization. This
      article will review indications for posterior cervical spine surgery, as well as
      the techniques that are currently available to help achieve the above-noted
      goals. We also report a recent retrospective review of 5-year data in treating
      posterior cervical trauma with lateral mass and pedicle screw fixation.

PMID- 15993117
TI  - Indications for surgery and stabilization techniques of the occipito-cervical
      junction.
AB  - Occipito-cervical (OC) instrumentation and fusion is indicated in traumatic
      atlanto-occipital dissociation and type III Anderson-Montesano occipital condyle
      fractures. The goals of surgery are to stabilize the mechanically compromised OC
      junction, correct deformity or displacement, and decompress compromised neural
      structures. The goals of instrumentation are to provide immediate stability,
      improve fusion rate, diminish the need for postoperative external immobilization,
      and decrease rehabilitation time. To successfully instrument the occipito
      cervical spine, a working knowledge of the anatomy of the occipital-cervical
      junction is imperative. A wide variety of stabilization techniques and
      instrumentation systems are currently available, each with its own advantages and
      disadvantages. With familiarity of the constraints and benefits of the available
      instrumentation systems, the individual fixation needs of a clinical situation
      can be fulfilled and successful patient outcomes can be achieved.

PMID- 15993118
TI  - Surgical management of odontoid fractures.
AB  - Odontoid fractures account for approximately 20% of all cervical fractures, with
      the majority being type II fractures according to the Anderson and D'Alonzo
      classification. The treatment of odontoid fractures is determined by multiple
      factors, including fracture type, presence of associated injuries, patient age,
      and patient comorbidities. It is generally well accepted that type I and type III
      injuries heal well with non-operative treatment. However, some type I injuries
      can be seen in association with occipito-atlantal dislocation; and some type III
      fractures can be closer to the neck of the odontoid (high and shallow based), and
      may act like a type II fracture, that is, with an increased probability of
      nonunion. The treatment of type II fractures remains controversial. Over the past
      decade, internal fixation has become an accepted treatment for unstable injuries
      of the cervical spine. Multiple surgical approaches have been proposed. This
      article reviews the various alternatives for treating odontoid fractures,
      attempting to give to the reader a broad perspective on the current techniques,
      including information taken from evidence-based medicine.

PMID- 15993119
TI  - Thoracic spine fractures.
AB  - Thoracic spine fractures have unique characteristics, and should be managed with
      specific criteria that are different from those used for thoracolumbar injuries.
      Fracture-dislocation injuries require high-energy injury, and should always be
      suspected in polytrauma patients with rib cage, sternum, cardiac, or pulmonary
      injuries. Although treatment is individualized, multisegmental posterior fixation
      sometimes combined with anterior decompression, is most commonly used. The
      authors review the current literature on this topic, and present their opinion on
      the management of such injuries.

PMID- 15993120
TI  - Management of posttraumatic kyphosis: surgical technique to facilitate a combined
      approach.
AB  - This report describes a variation of the "posterior-anterior-posterior" surgical
      techniques to correct posttraumatic kyphosis of the thoracic and lumbar spine
      with the USS internal fixator. This modification is based on the use of
      "temporary screws" to mark the entrance of the pedicles in the first stage of the
      operation (posterior approach, with the patient in prone position). Approaching
      both columns of the spine simultaneously facilitates correction of the kyphotic
      defect and permits 360 reconstruction of the spine.

PMID- 15993121
TI  - Less invasive anterior column reconstruction in thoracolumbar fractures.
AB  - Posterior short-segment pedicle screw constructs are commonly used for reduction
      and fixation of traumatic thoracolumbar spine fractures. Although this technique
      is usually simple and effective, complications such as loss of fixation or
      recurrence of deformity are common because of the insufficiency of the damaged
      anterior column. Anterior approaches to address this deficiency are associated
      with high morbidity and complications. We have developed a technique to reduce
      and support the fractured anterior column through a transpedicular approach.
      Balloon-assisted-endplate-reduction (BAER) followed by vertebroplasty (VTP) with
      calcium phosphate cement in combination with short segment pedicle screw
      construct seem to be a safe and effective technique to reconstruct the anterior
      column in a less invasive manner. In this article, the rationale behind this
      technique, experimental studies, and the first clinical results are discussed.

PMID- 15993122
TI  - Fractures of thoracolumbar spine: monosegmental fixation.
AB  - We studied 18 patients with fractures of the thoracolumbar spine undergoing the
      surgical treatment of posterior monosegmental fixation and arthrodesis. Patient
      follow-up ranged from 2-12 years (mean: 6.65+/-2.96), and the patients were
      assessed by clinical evaluation, radiographic study, and functional evaluation.
      The parameters used for clinical evaluation were the Denis pain scale and
      neurological evaluation by the Frankel scale, while a subjective evaluation of
      the final result was made by the patients themselves. Kyphosis of the injured
      vertebral segment, the height of the disk of this segment, and the presence of
      bone reabsorption around the implant were the parameters used for radiographic
      evaluation. Functional evaluation was performed by: the Denis work scale; the
      Oswestry disability index; and the SF-36 questionnaire. Clinical evaluation
      revealed low residual pain rates and a high level of patient satisfaction with
      the final result. Functional evaluation showed that 95.5% of the patients
      returned to work on a full-time basis, presented with a low disability index
      (Oswestry=10.33) and followed the profile of the North American population when
      assessed by the SF-36 questionnaire. Radiographic evaluation revealed increased
      kyphosis in the fixed vertebral segment during the late postoperative period,
      accompanied by a reduced height of the intervertebral disk. There was no implant
      break, and no signs of pseudoarthrosis were observed in any patient. The
      clinical, functional, and radiographic results observed show that posterior
      monosegmental fixation is an adequate and satisfactory procedure to be used in
      specific types of thoracolumbar spine fractures.

PMID- 15993123
TI  - The role of 3-D rotational x-ray imaging in spinal trauma.
AB  - The most widely used imaging devices in trauma spine surgery are fluoroscopy and
      computed tomography. Both techniques have their specific pros and cons and expose
      both patient and operating staff to considerable radiation during image
      acquisition. Three-dimensional-rotational x-ray imaging (3-DRX) is a relatively
      new technique in which a C-arm is moved around the patient to allow for an
      "acquisition run" during which multiple fluoroscopy images are obtained. The
      images can subsequently be processed on a workstation into a 3-D volume, which
      can then be manipulated in a similar way to 3-D computed tomography data. The 3
      DRX technique combines the advantages of both fluoroscopy and computed
      tomography: fast visual feedback and high resolution multiplanar reformatted
      images, respectively, and could be used in an intraoperative setting. In this
      paper some technical aspects of 3-DRX imaging and its potential role in spinal
      trauma treatment are presented.

PMID- 15993124
TI  - Erwin Bunning and Tony Lees, two giants of chronobiology, and the problem of time
      measurement in insect photoperiodism.
AB  - This paper examines the views of Erwin Bunning and Tony Lees on the mechanism of
      photoperiodic time measurement, the former advocating a circadian basis for the
      phenomenon and the latter a non-circadian hourglass-like timer. This difference
      in opinion led to a protracted split among workers on photoperiodism, some
      supporting an oscillatory clock and others an "hourglass", and gave rise to the
      often stated opinion that the two forms of time measurement were mutually
      exclusive. This paper, however, suggests that both oscillatory and hourglass-like
      properties are to be seen in insect photoperiodism. Furthermore, the differences
      between the two apparently conflicting models may be resolved if, following
      Bunning, "hourglasses" are regarded as damping circadian oscillators, with the
      more self-sustained (clearly oscillatory) and more highly damped (hourglass-like)
      responses being parts of a continuous series. Since circadian rhythmicity is an
      all-pervading and fundamental aspect of insect biology, currently opening up to
      genetic and molecular analysis, recognition of the basic similarity of a wide
      range of insect photoperiodic timers may help to unravel the biochemical nature
      of the mechanism(s) involved.

PMID- 15993125
TI  - How similar are daily and seasonal biological clocks?
AB  - Daily and seasonal timing systems in insects have usually been supposed to share
      similar mechanisms, because both rely in large measure on information from the
      daily light-dark cycle: daily clocks can ensure that activity coincides with the
      appropriate time of day, and seasonal time is indicated most reliably by
      daylength. However, several lines of evidence suggest that the systems are
      different. For example, receptor features, photosensitive pigments, clocks, and
      the effectors that mediate responses to information derived from the clock may
      have different daily, seasonal and general functions and properties, and several
      different systems are known. There are many different additional elements in the
      seasonal response. Therefore, these responses may not rely on similar timing
      mechanisms, despite the long-standing belief that the seasonal clock has
      circadian components. Such a difference would be consistent with the fact that
      temporal responses serve a very wide range of purposes, meeting many different
      ecological needs on different time frames. Consequently, understanding the
      seasonal relevance of the photoperiodic responses is more important than
      revealing any possible involvement with circadian systems.

PMID- 15993126
TI  - Temporal variation in overwintering gene expression and respiration in the
      solitary bee Megachile rotundata.
AB  - Partial clones of Megachile rotundata HSP90, HSP70, HSC70 and actin were
      developed by RT-PCR. These clones were used to generate probes to screen for the
      expression of their respective transcripts in heat-shocked pupae and in
      diapausing prepupae through post-diapausing pupae. Northern blot analysis
      revealed transcript sizes for MrHSP90, MrHSP70, MrHSC70, and Mractin of 3.6, 2.3,
      2.5, and 1.4kb, respectively. MrHSP90 and MrHSP70 were highly upregulated in post
      diapausing pupae exposed to 40 degrees C for 1h, while MrHSC70 was only slightly
      induced by heat shock. Levels of MrHSC70 and MrHSP90 showed little change between
      field collected diapausing prepupae and post-diapausing pupae. In contrast,
      MrHSP70 was highly upregulated in diapausing prepupae and Mractin was at or below
      the level of detection in diapausing prepupae. Transferring field reared
      overwintering prepupae in February to 25 degrees C for 3 days induced an
      expression pattern of MrHSP70 and Mractin more typical of post-diapausing bees,
      indicating the likelihood that the transition to post-diapause development had
      occurred prior to February. However, measurements revealed possible cyclic
      respiration patterns, including low respiratory quotient (RQ) values during
      February and March and a transition during April to more continuous respiration
      with elevated RQ values.

PMID- 15993127
TI  - Temporal expression patterns of diapause-associated genes in flesh fly pupae from
      the onset of diapause through post-diapause quiescence.
AB  - Distinct differences in the temporal expression patterns of genes associated with
      pupal diapause were noted in the flesh fly, Sarcophaga crassipalpis. The first
      change observed was a decline in expression of the gene encoding heat shock
      protein 90 (hsp90) 2 days after pupariation (1 day before the pupa reaches the
      phanerocephalic stage characteristic of diapause). In contrast, hsp23 and hsp70
      transcripts were undetectable in nondiapause samples and d1-d4 diapause
      programmed pupae, but were up-regulated just after the start of diapause, 5 days
      after pupariation. An increase of glycerol content in diapausing pupae was also
      noted at the start of diapause. The gene encoding proliferating cell nuclear
      antigen (pcna) was diapause down-regulated, and this occurred in two phases, with
      the first decline in expression 7 days after pupariation and a second decline in
      the level of expression on day 14. For pupae held at 20 degrees C for 20 days and
      transferred to 10 degrees C, diapause ended after 90-100 days at the lower
      temperature. However, pupae remained in a state of post-diapause quiescence (d100
      d150) and sustained diapause-like hsp and pcna expression patterns until adult
      development was initiated. Glycerol concentrations and survival declined during
      the post-diapause phase. This study suggests a distinct sequence in the pattern
      of gene expression at the onset of diapause, but the genes we have monitored do
      not contribute to the switch to covert developmental potential at the transition
      from diapause to post-diapause quiescence.

PMID- 15993128
TI  - Gene expression of heat-shock proteins (Hsp23, Hsp70 and Hsp90) during and after
      larval diapause in the blow fly Lucilia sericata.
AB  - Genes encoding heat-shock protein 23 (Hsp23), Hsp70 and Hsp90 were cloned from
      Lucilia sericata to examine whether their expression is related to the regulation
      of its larval diapause. The level of all three Hsps mRNAs was consistently low
      irrespective of diapause status. These results indicate that expression of Hsp23,
      Hsp70 and Hsp90 is not regulated in response to diapause, in contrast to the
      flesh fly Sarcophaga crassipalpis that shows upregulation of Hsp23 and Hsp70 and
      downregulation of Hsp90 during its pupal diapause. On the other hand, Hsp90
      transcripts were regulated developmentally in nondiapause larvae of L. sericata,
      i.e., they were at low levels after cessation of feeding but were considerably
      upregulated a day before pupariation, suggesting that Hsp90 is involved in a
      developmental process that occurs between the cessation of feeding and
      pupariation. When diapause larvae were transferred to all of the conditions that
      terminate diapause and allow postdiapause development, Hsp90 transcripts were
      promptly upregulated. These results indicate that Hsp90 may serve as an early
      marker to predict diapause termination in this species.

PMID- 15993129
TI  - Photoperiod-sensitive developmental delay in facet mutants of the drosophilid
      fly, Chymomyza costata and the genetic interaction with timeless.
AB  - Previously, we demonstrated that the biological clock gene, timeless (tim), is
      potentially involved in photoperiodic diapause induction in the larvae of the
      drosophilid fly Chymomyza costata. Suppression of tim transcription was
      inevitably associated with the loss of diapause induction even under diapause
      promoting short-day conditions. In the present paper, I report a novel gene,
      facet (fa), which may genetically interact with tim in photoperiodically
      controlled larval development in this species. I demonstrated the effect of
      photoperiod on the development of fa morphological mutants. Developmental delay
      was remarkable in fa larvae under a diapause-preventing photoperiod, 16 h light:
      8 h dark/day, in which the wild-type individuals showed normal and synchronous
      development. The delay was recovered by extension of the light phase of daily
      light/dark cycles or the introgression of a deficient tim allele.

PMID- 15993130
TI  - Is period gene causally involved in the photoperiodic regulation of reproductive
      diapause in the linden bug, Pyrrhocoris apterus?
AB  - Earlier experiments demonstrated a strong up-regulation of per mRNA in wild-type
      (Wt) females of Pyrrhocoris apterus reared under diapause-inducing short days,
      while per mRNA levels were low in females of two non-diapause mutant strains
      (Nd), irrespective of photoperiod. In the present study, different sequences of
      per DNA in two strains of geographically different origin enabled us to analyse
      genetic linkage between the per gene and the Nd phenotype. Crosses between Wt
      females originating from C. Budejovice (Czech Republic) and Nd males originating
      from Lyon (France) resulted in F(2) progeny where 411 females entered diapause
      under short days and 120 females were reproducing. Thus, the segregation was very
      close to the 3:1 ratio in favour of diapause females, suggesting that the Nd
      trait behaves as a single autosomal recessive. Analysis of DNA in 20 females of
      the F(2) progeny revealed that their phenotype was not linked to the per
      genotype. We conclude that the per gene is not primarily responsible for the
      block to diapause photoresponsiveness in Nd mutants and its role, if any, is
      downstream from other gene(s) controlling diapause. This is the first attempt at
      genetic linkage analysis between a bona fide circadian clock gene and
      photoperiodism in a "non-drosophilid" species.

PMID- 15993131
TI  - Photoperiodic modulation of circadian rhythms in the cricket Gryllus bimaculatus.
AB  - The waveform and the free-running period of circadian rhythms in constant
      conditions are often modulated by preceding lighting conditions. We have examined
      the modulatory effect of variable length of light phase of a 24h light cycle on
      the ratio of activity (alpha) and rest phase (rho) as well as on the free-running
      period of the locomotor rhythm in the cricket Gryllus bimaculatus. When
      experienced the longer light phases, the alpha/rho-ratio was smaller and the free
      running period was shorter. The magnitude of changes in alpha/rho-ratio was
      dependent on the number of cycles exposed, while the free-running period was
      changed by a single exposure, suggesting that there are separate regulatory
      mechanisms for the waveform and the free-running period. The neuronal activity of
      the optic lobe showed the alpha/rho-ratio changing with the preceding
      photoperiod. When different photoperiodic conditions were given to each of the
      two optic lobe pacemakers, the alpha/rho-ratio of a single pacemaker was rather
      intermediate between those of animals treated with either of the two conditions.
      These results suggest that the storage of the photoperiodic information occurs at
      least in part in the optic lobe pacemaker, and that the mutual interaction
      between the bilateral optic lobe pacemakers is involved in the photoperiodic
      modulation.

PMID- 15993132
TI  - Effects of temperature during chilling and pre-chilling periods on diapause and
      post-diapause development in a katydid, Eobiana engelhardti subtropica.
AB  - In Eobiana engelhardti subtropica, early laid eggs reach the diapause stage in
      early autumn. For long periods before winter, the eggs are exposed to
      temperatures higher than their theoretical lower threshold for development. In
      contrast, late-laid eggs cannot reach their diapause stage before winter. Our
      study showed that E. e. subtropica copes with these difficulties via the thermal
      response involving embryonic diapause. In this katydid, the almost fully
      developed embryo undergoes an obligatory diapause. When diapause eggs were
      maintained at a temperature of 20 degrees C or higher, diapause persisted for a
      long time. Diapause was effectively terminated by temperatures ranging from 1 to
      11 degrees C, and hatching occurred successfully at temperatures from 11 to 15
      degrees C. In addition to the chilling temperature, pre-chilling temperature
      modified diapause intensity and hatching time. Diapause eggs hatched earlier
      after chilling when the pre-chilling temperature was lower, within a range of
      14.5-25 degrees C. Thus, the low-temperature requirement for diapause termination
      prevents early laid eggs from untimely hatching in autumn, and low temperatures
      before and during winter decrease diapause intensity and shorten the hatching
      time in the following spring. When eggs were chilled before diapause, they
      tolerated chilling and averted diapause. Thus, even if eggs encounter low
      temperatures before diapause, they can hatch in the following spring.

PMID- 15993133
TI  - Induction of anhydrobiosis in fat body tissue from an insect.
AB  - The larva of the African chironomid Polypedilum vanderplanki can withstand
      complete desiccation. Our previous reports revealed that even when the larva is
      dehydrated without a brain, it accumulated a great amount of trehalose and
      successfully went into anhydrobiosis. In this paper we determined the viability
      after rehydration in tissues from the larvae followed by complete dehydration.
      Only fat-body tissues that were the main producer of trehalose could be preserved
      in a dry state at room temperature for an extended period of more than 18 months
      in a viable form. Thus we have confirmed that the central nervous system is not
      involved in the induction of anhydrobiosis, even in this complex multicellular
      organism.

PMID- 15993134
TI  - Stability of acetylcholine chloride solution in autonomic testing.
AB  - Acetylcholine (ACh) is the neurotransmitter used as an agent to evoke a sudomotor
      axon reflex response in autonomic testing. Adequate stimulus of postganglionic
      axons requires ACh solutions to be stable, but its stability in the clinical
      laboratory is uncertain. We evaluated the stability of standard (0.55 M) ACh
      solutions stored at temperatures of -20 degrees C, 4 degrees C, 25 degrees C, and
      50 degrees C for 10 time points between 0 and 84 days. ACh and choline (Ch) were
      measured by reverse-phase HPLC with electrochemical detection using an
      Acetylcholine/Choline Assay Kit. Linear regressions of ACh and Ch standards were
      used to calculate the levels in the stored samples. The inherent levels of Ch
      were used as the internal standard. Regression analyses were used to examine the
      effects of length of storage and temperature. The samples of ACh stored at -20
      degrees C and 4 degrees C showed an extremely small breakdown over the 84-day
      period and had no evidence to show the regression lines differed. ACh solution
      stored at 25 degrees C was stable for about 28 days, after such time, modest
      breakdown occurs. At a temperature of 50 degrees C, ACh showed a rapid breakdown
      after 1 day. We conclude ACh solution should not be stored at room temperature
      for more than 28 days and should not be exposed to higher temperatures to assure
      an adequate axon stimulus.

PMID- 15993135
TI  - Incidence of ulnar neuropathy at the elbow in the province of Siena (Italy).
AB  - BACKGROUND: Although ulnar neuropathy at the elbow (UNE) is the second most
      frequent focal peripheral neuropathy of the upper limb after carpal tunnel
      syndrome (CTS), no figures on its prevalence or incidence in the general
      population have been reported. OBJECTIVE: To determine the incidence of UNE in a
      general population. METHODS: Retrospective study to identify newly diagnosed
      cases on the basis of clinical symptoms or signs and slowing of motor conduction
      velocity of the ulnar nerve across the elbow or surgical evidence of nerve
      compression in the elbow region. In the 5-year period from 1995 to 1999, cases
      among residents in Siena Province (Italy) were identified from medical records of
      electromyographic services of Local Health District no. 7 and from hospital
      medical records coded ICD 354.2, 04.49 and 04.6. Siena province has a population
      of 251,930. RESULTS: In the 5-year period, 311 cases (112 women and 199 men, mean
      age 56 years, range 15-86) were identified. The mean annual crude incidence was
      24.7 cases per 100,000 person-years, and the standardized incidence was 20.9. The
      sex-specific incidences were 32.7 for men and 17.2 for women. The mean annual
      crude and sex-specific incidences remained constant during the study period. The
      age-specific incidences of whole population and both genders showed an increasing
      trend with decade of age. The incidence of "possible", "probable" and "definite"
      UNE cases, classified according to level of motor conduction velocity anomalies
      and evidence of surgical compression of the ulnar nerve at the elbow, was 4.3,
      10.6, and 9.8, respectively. The residents of a health subdistrict where manual
      work is dominant had a higher male-specific incidence (57.1) than other areas.
      CONCLUSIONS: This is the first published study on the incidence of UNE. The
      incidence was higher in males than females and about one-thirteenth that reported
      for CTS in part of the present geographic area.

PMID- 15993136
TI  - Bilateral induction of the S-100A9 gene in response to spreading depression is
      modulated by the cyclooxygenase-2 activity.
AB  - Cyclooxygenase-2 (COX-2) was reported to be induced in the infarcted human brain.
      Spreading depression (SD) is thought to play a role in this induction. In this
      study, we correlated the expression of SD-associated genes with COX-2 production
      in brains after SD. Rats were divided into 3 groups: rats that did not undergo SD
      (group I saline controls, n=7), rats that underwent unilateral SD as a result of
      KCl application (group II, n=9), and rats that were pretreated with the selective
      COX-2 inhibitor, JTE-522 3 h before the induction of SD (group III, n=7). The
      expression of the SD-associated genes, S-100A9, and mitogen-activated
      proteinkinase phosphatase (cpg21) was analyzed 2 h later using a cDNA array. In
      group II, COX-2 and cpg21 mRNA expression, as determined by RT-PCR, were
      significantly upregulated in the hemisphere undergoing SD. While the expression
      of S-100A9 mRNA was bilaterally upregulated in these animals, this expression was
      significantly reduced in group III, and was accompanied by reduced bilateral
      production of PGE(2). Thus, the bilateral induction of expression of the S-100A9
      gene in response to SD was associated with COX-2 activation.

PMID- 15993137
TI  - MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment
      in multiple sclerosis.
AB  - OBJECTIVES: MRI T2 hypointensity in multiple sclerosis (MS) gray matter,
      suggesting iron deposition, is associated with physical disability, disease
      course, lesion load, and brain atrophy. Ambulatory dysfunction limits quality of
      life; however correlation with conventional MRI remains poor. METHODS: Normalized
      intensity on T2-weighted images was obtained in the basal ganglia, thalamus, red
      nucleus, and dentate nucleus in 47 MS patients and 15 healthy controls. Brain T1
      hypointense and FLAIR-hyperintense lesion volume, third ventricle width, brain
      parenchymal fraction and timed 25 foot walk (T25FW) were measured in the MS
      group. RESULTS: T2 hypointensity was present throughout gray matter in MS vs.
      controls (all p<0.01). Dentate T2 hypointensity was the only MRI variable
      significantly correlated with T25FW (Pearson r=-0.355, p=0.007) and was also the
      best MRI correlate of physical disability (EDSS) score in regression modeling (r=
      0.463, R(2)=0.223, p=0.004). CONCLUSIONS: T2 hypointensity is present in
      subcortical gray matter nuclei in patients with MS vs. normal controls. Dentate
      nucleus T2 hypointensity is independently related to ambulatory impairment and
      disability, accounting for more variance than conventional lesion and atrophy
      measures. This study adds more weight to the notion that T2 hypointensity is a
      clinically relevant marker of tissue damage in MS.

PMID- 15993138
TI  - Alterations of ionized Mg2+ in human blood after exercise.
AB  - Magnesium (Mg) is the second most abundant intracellular cation with modulating
      properties in a number of metabolic processes, e.g. in glycolysis, and
      intracellular signalling processes, e.g. regulation of ion channels and
      transporters. There are conflicting data available about the regulation of Mg in
      blood cells during exercise. Moreover, there are no data available about changes
      of the metabolic important fraction of ionized Mg(2+) both in blood and in blood
      cells during exercise. The present study investigated the changes of ionized
      Mg(2+) and total Mg concentration in different compartments after a stepwise
      treadmill ergometer test. Intracellular ionized Mg(2+) of thrombocytes and
      erythrocytes was determined by the magnesium sensitive fluorescent dyes mag-fura
      2 and Mag-Green using fluorescence spectroscopy and flow cytometry, respectively.
      Ionized Mg(2+) in blood/serum was measured by an ion-sensitive microelectrode.
      Total cellular and serum Mg concentration were investigated using atomic
      absorbance spectroscopy and photometry, respectively. The present results shown
      that at the end of the ergometer test, ionized Mg(2+) in both blood and serum and
      total serum Mg decreased. In contrast, intracellular concentration of ionized Mg
      increased in both thrombocytes and erythrocytes. Total intracellular Mg was
      unchanged making a Mg(2+) shift between the intra- and extracellular compartment
      unlikely. The present study therefore demonstrated opposite changes of the ratio
      [ionized Mg(2+)]/[total Mg] in the intracellular and the extracellular
      compartment after anaerobic exercise. In in vitro experiments, similar changes of
      ionized Mg(2+) in both compartments could be mimicked by application of weak
      acids like propionic and lactic acid. It is concluded changes in the fraction of
      ionized Mg(2+) should be high enough to influence intracellular signalling and
      metabolic processes.

PMID- 15993139
TI  - Use of composite data sets for source-tracking enterococci in the water column
      and shoreline interstitial waters on Pensacola Beach, Florida.
AB  - Sources of Enterococcus faecalis isolates from Pensacola Beach, FL. were
      identified using a library-based approach by applying the statistical method of
      average similarity to single and composite data sets generated from separate
      analyses. Data sets included antibiotic resistance analysis (ARA), rep
      fingerprints, and fatty acid methyl ester (FAME) profiles. Use of a composite
      data set composed of ARA and rep-fingerprints, added to the confidence of the
      identifications. The addition of FAME data to composite data sets did not add to
      the confidence of identifications. Source identification was performed to better
      understand risk associated with higher densities of enterococci found in swash
      zone interstitial water (SZIW) as compared to adjacent bathing water on Pensacola
      Beach, FL. The "swash zone" is that area of the beach continually washed over by
      waves. As the potential sources of enterococci were limited in this environment,
      only two library units, sea gull and human, were constructed. Identification of
      the beach isolates using a composite data set indicated a sea gull origin. The
      clonality of the beach isolates suggested that the beach environment selects
      certain subspecies of E. faecalis.

PMID- 15993140
TI  - Concentrations of heavy metals in sediment and organisms during a harmful algal
      bloom (HAB) at Kun Kaak Bay, Sonora, Mexico.
AB  - In early April 2003, fishermen from Kino Bay Sonora alerted us about a massive
      die-off of fish and mollusks occurring at Kun Kaak Bay. Phytoplankton samples
      taken on 17 May 2003 reported the presence of a harmful algal bloom composed of
      Chatonella marina, Chatonella cf. ovata, Gymnodinium catenatum and Gymnodinium
      sanguineum. On 22 of May, we collected samples of water, sediment and organisms
      at the affected area. Physicochemical parameters and nutrients were measured in
      water samples from different depths. Sediment and benthic organisms were analyzed
      for Cd, Cu, Zn, Pb and Hg. We found concentrations of heavy metals higher than
      background levels for this area. Cadmium and Lead concentrations in sediment from
      the HAB area were up to 6x greater than background levels and Cd in mollusks was
      8x greater than regulations allow. A relationship between elevated Cd and Pb
      concentrations in sediment and the survival of toxic dinoflagellates is
      suspected.

PMID- 15993141
TI  - Comparison of mussels and semi-permeable membrane devices as intertidal monitors
      of polycyclic aromatic hydrocarbons at oil spill sites.
AB  - Side-by-side comparisons of polycyclic aromatic hydrocarbon (PAH) concentrations
      in resident blue mussels (Mytilus trossulus) and in semi-permeable membrane
      devices (SPMDs) were made at four sites in Prince William Sound, Alaska. SPMDs
      were deployed for approximately 30 days on the surface of the beach sediment at
      three tidal elevations on each shore and in 0.5 m deep open pits in the middle
      intertidal zone. Total PAH (TPAH) concentrations in mussels and in SPMDs were
      correlated, but the PAH compositions were different. The lower molecular weight
      PAH were relatively more abundant in the SPMDs than in the mussels at oiled and
      HA sites. TPAH concentrations in SPMDs deployed in pits and mussels collected
      adjacent to those pits at oiled sites were higher than in SPMDs and mussels from
      non-pitted SPMD locations approximately 3-15 m from the pits. Pitting released
      buried oil making its PAH bioavailable. SPMDs deployed in the supratidal zone
      (+4.0 m tidal elevation) were exposed to atmospheric contaminants for a large
      fraction of the deployment time and accumulated primarily pyrogenic (combustion
      sourced) PAH from the atmosphere. The SPMD strips supplied by the manufacturer
      contained significant amounts (approximately 125 ng/strip) of primarily alkylated
      2-3 ring PAH. These blank levels make SPMDs unsuitable for shoreline assessments
      when environmental PAH concentrations are low. Consequently, where available,
      mussels are recommended for use in assessments of the bioavailability of buried
      oil residues sequestered in intertidal sediments following an oil spill. Mussels
      are the preferred monitoring tool when the assessments involve food-chain
      effects. At locations where the absence of mussels necessitates the use of SPMDs
      or other passive sampling devices, their limitations need to be carefully
      considered in the interpretation of results.

PMID- 15993142
TI  - Changes of microbial populations in a ship's ballast water and sediments on a
      voyage from Japan to Qatar.
AB  - Colony-forming eutrophic marine microorganisms in ballast water were counted in
      samples taken on board in 2002 and 2003. In the ballast water in Japan, viable
      cell numbers were highly variable but not by more than 10(5.1) colony-forming
      units (CFU)ml(-1) regardless of season. Even when ballast water was discharged
      offshore, values varied but not by more than 10(5.0) CFUml(-1). The effectiveness
      of the ballast water exchange was unconfirmed, except for the February 2003
      voyage. No microbial colonies were counted in the reloaded ballast water in the
      high seas on that voyage, which contributed to the reduction of the total number
      of viable cells sampled in the discharged ballast water at the Ras Laffan port in
      Qatar. In sediment samples, the values of 10(5.2) - 10(6.0) CFUml(-1) were
      estimated for all seasons in which voyages took place. The maximum of the marine
      Vibrio species, 110 CFUml(-1), was observed in the ballast water sample taken in
      July 2003. The estimated total viable cell numbers in sediments were higher than
      those counted in the ballast water throughout the experiments, indicating the
      importance of sediment management as well as ballast water management on vessels
      traveling from Japan.

PMID- 15993143
TI  - Biomarkers of contaminant exposure: results of a field study with flounder
      (Platichthys flesus) from the southern Baltic Sea.
AB  - The results of the present study are based on enzyme biomarker measurements in
      flounder (Platichthys flesus), a flatfish species that is widely distributed in
      Baltic coastal waters. The fish were collected from known pollution gradients and
      from reference areas regarded as relatively free of anthropogenic input. Muscular
      cholinesterases (ChEs), hepatic glutathione S-transferase (GST), and hepatic
      ethoxyresorufin-O-deethylase (EROD) activities were measured in each sampled
      specimen of flounder. Generalized linear models (GLM) were used to analyze the
      dependence of the enzyme activity on sampling year and area as well as on the
      biological parameters of the fish. Statistically significant differences in the
      activities of the measured biomarkers were observed between reference and
      contaminated sites. ChEs and GST activities differed with gender. The results of
      this study suggest that the location and year of sampling have a significant
      impact on the activity of all the measured biomarkers.

PMID- 15993144
TI  - The effects of sand extraction on the macrobenthos of a relict sands area
      (northern Adriatic Sea): results 12 months post-extraction.
AB  - Sands for the nourishment of beaches along the Emilia-Romagna coast (northern
      Adriatic Sea) were dredged from an offshore area characterised by relict sands
      formed during the last Adriatic post-glacial transgression. The short-term
      effects of the sand extraction on macrozoobenthic communities were investigated
      before, during and 1, 6 and 12 months after dredging at three impacted stations
      and seven control stations. Sand extraction activities did not significantly
      influence the granulometry and %TOC in the sediment but caused almost complete
      defaunation at dredging stations. Yet, just 12 months after the extraction, the
      recolonisation of communities at the impacted stations was at an advanced stage.
      Unlike other studies on the effects of extraction of marine sand, no significant
      settlement of opportunistic species was observed. The limited impact of the sand
      extraction operation on the physical characteristics of the sediment and
      hydrological-sedimentary characteristics in the relict sand area should aid its
      rapid recovery and the restoration of the original community in a short period of
      time (2-4 years after dredging).

PMID- 15993145
TI  - PCBs and chlorinated pesticides (DDTs, HCHs and HCB) in the atmosphere of the
      southwest Atlantic and Antarctic oceans.

PMID- 15993146
TI  - Biodegradation of cyclodextrins in soil.
AB  - Cyclodextrins, especially random methylated betaCD (RAMEB) and hydroxypropyl
      betaCD (HPbetaCD), are becoming common enhancing additives in the bioremediation
      of soils formerly contaminated by hydrocarbons and/or other poorly bioavailable
      organic pollutants. Therefore, their degradation in the soil, particularly the
      most persistent RAMEB, has been of great concern. Like oil contaminants, these
      additives should be biodegradable via an environmentally safe technology. Hence,
      in this paper, the biodegradability of eight different cyclodextrins (CDs) in
      four different soils was examined under various treatment conditions in
      laboratory and pilot scale field experiments. This paper is the first report on
      the potential biological fate of CDs studied under a large variety of
      environmental conditions and in different soil ecosystems. Data on the potential
      relationship between CD biodegradation and the biological removal of hydrocarbons
      in the CD-amended contaminated soils are also given. All CDs were found to be
      more or less biodegradable; even the most persistent RAMEB was depleted from
      soils under favourable conditions. In the field experiments, the depletion of
      RAMEB to about 40% of its initial level was observed for a period of 2 years in
      hydrocarbon-contaminated soils of high organic matter and cell concentration.

PMID- 15993147
TI  - Activated carbon from industrial solid waste as an adsorbent for the removal of
      Rhodamine-B from aqueous solution: kinetic and equilibrium studies.
AB  - The activated carbon was prepared using industrial solid waste called sago waste
      and physico-chemical properties of carbon were carried out to explore adsorption
      process. The effectiveness of carbon prepared from sago waste in adsorbing
      Rhodamine-B from aqueous solution has been studied as a function of agitation
      time, adsorbent dosage, initial dye concentration, pH and desorption. Adsorption
      equilibrium studies were carried out in order to optimize the experimental
      conditions. The adsorption of Rhodamine-B onto carbon followed second order
      kinetic model. Adsorption data were modeled using both Langmuir and Freundlich
      classical adsorption isotherms. The adsorption capacity Q0 was 16.12 mg g(-1) at
      initial pH 5.7 for the particle size 125-250 microm. The equilibrium time was
      found to be 150 min for 10, 20 mg l(-1) and 210 min for 30, 40 mg l(-1) dye
      concentrations, respectively. A maximum removal of 91% was obtained at natural pH
      5.7 for an adsorbent dose of 100mg/50 ml of 10 mg l(-1) dye concentration and
      100% removal was obtained when the pH was increased to 7 for an adsorbent dose of
      275 mg/50 ml of 20 mg l(-1) dye concentration. Desorption studies were carried
      out in water medium by varying the pH from 2 to 10. Desorption studies were
      performed with dilute HCl and show that ion exchange is predominant dye
      adsorption mechanism. This adsorbent was found to be both effective and
      economically viable.

PMID- 15993148
TI  - Inactivation of antineoplastics in clinical wastewater by electrolysis.
AB  - Wastewater from clinical institutions contains a considerable amount of toxic
      substances. Among the toxic substances, antineoplastics may induce
      carcinogenesis, teratogenesis, and the emergence of mutant microorganisms in the
      environment. Although the incineration or chemical treatments of disposed
      antineoplastics are recommended, a high energy during incineration and a careful
      quality control during chemical treatment are required. In this study, we
      determined the conditions for the electrolytic treatment of an antineoplastic,
      epirubicin hydrochloride (EH), using two platinum electrodes with a constant
      current of 100 mA. We analyzed the cytotoxicity, mutagenicity and antibacterial
      activity of electrolyzed EH and compared them with those of unelectrolyzed EH.
      Nearly 100% cytotoxicity, mutagenicity and antibacterial activity were eliminated
      and HPLC did not detect an EH molecule, in the case of electrolysis for 6 h. We
      also examined the biological cytotoxicities of electrolyzed irinotecan
      hydrochloride, vincristine sulfate, mitomycin C, paclitaxel, methotrexate and
      cisplatin, and found that 72.1-99.999% toxicity was eliminated by electrolysis
      under the same conditions. The biological toxicity of a mixture of these drugs
      was determined to be decreased by approximately 99% by electrolysis under the
      same conditions.

PMID- 15993149
TI  - FIA/MS analysis of temporally ozonated benzo[a]pyrene and pyrene and their
      reaction products: inhibition of gap junction-mediated intercellular
      communication.
AB  - In this study, the polycyclic aromatic hydrocarbons, benzo[a]pyrene (BaP) and
      pyrene, were subjected to temporal ozonation. The products from ozonation of 5 mg
      l(-1) BaP and 5 mg l(-1) pyrene, for varying time intervals (0, 1, 2, 3, 4, 5, 6,
      8, 10, 20, and 30 min) were tested for their effects on gap junction-mediated
      intercellular communication (GJIC) in Clone 9 rat liver cells. Additionally, the
      ozonation products were also analyzed by flow injection analysis/mass
      spectrometry (FIA/MS) and the results were compared with the toxicity observed in
      the GJIC assay. Treatment of the Clone 9 cells with 5 mg l(-1) of ozonated BaP
      products resulted in a decrease in GJIC that was inversely proportional to the
      length of ozonation. The products from 1 min of ozonation resulted in a 92%
      decrease in the rate of GJIC, but with >5 min ozonation, the products did not
      suppress GJIC. In contrast, pyrene (0.5 mg l(-1)) required >10 min of ozonation
      to alleviate its effects on GJIC. FIA/MS, using atmospheric pressure chemical
      ionization (APCI), demonstrated products with higher molecular weights (MW) than
      their corresponding parent compounds, BaP (MW 252) and pyrene (MW 202). Ozonation
      of pyrene formed significantly fewer products than BaP. More importantly, pyrene
      ozonation products were constant from 1 to 10 min, while BaP ozonation products
      seemed to vary between time intervals. With the longer ozonation times (20 and 30
      min), BaP and pyrene formed similar products (m/z peaks 157, 111, and 96). The
      suppression of GJIC by ozonated products seemed to correlate with oxidation of
      the aromatic ring framework. Further oxidation (longer ozonation times) to lower
      MW products correlated with restoration of normal GJIC.

PMID- 15993150
TI  - Fate and mobility of pharmaceuticals in solid matrices.
AB  - The sorption and mobility of six pharmaceuticals were investigated in two soil
      types with different organic carbon and clay content, and in bacterial biomass
      (aerobic and anaerobic). The pharmaceuticals examined were carbamazepine,
      propranolol, diclofenac sodium, clofibric acid, sulfamethoxazole and ofloxacin.
      The sorption experiments were performed according to the OECD test Guideline 106.
      The distribution coefficients determined by this batch equilibrium method varied
      with the pharmaceutical tested and the solid matrix type. Ofloxacin was
      particularly strongly adsorbed (except of the case of using anaerobic biomass for
      the solid matrix) while clofibric acid was found to be weakly adsorbed. The fate
      of pharmaceuticals in soil was also assessed using lysimeters. Important
      parameters that were studied were: the pharmaceutical loading rate and the
      hydraulic loading rate for adsorption and the rate and duration of a "rain" event
      for desorption. Major differences in the mobility of the six pharmaceuticals were
      observed and correlated with the adsorption/desorption properties of the
      compounds.

PMID- 15993151
TI  - The degradation of endocrine disruptor di-n-butyl phthalate by UV irradiation: a
      photolysis and product study.
AB  - The direct photolysis of an important endocrine disruptor compound, di-n-butyl
      phthalate (DBP), has been investigated under monochromatic UV irradiation at 254
      nm over a wide pH range (3-11). The investigation was carried out under idealized
      conditions and has considered both reaction kinetics and the degradation
      mechanism. It was found that more than 90% of DBP can be degraded within an hour
      of irradiation in water. A simple model has been developed and used to predict
      the initial DBP photolysis rate constant at different pH values and initial DBP
      concentrations. The major decomposition mechanism of DBP is believed to involve
      the hydrolytic photolysis of the carbon in the alpha and/or beta-position of the
      ester chain with the production of aromatic carboxylic derivatives. Additionally,
      multi-degradation pathways are proposed for acid-catalyzed hydrolytic photolysis
      (pH 3-5), which was found to be useful in explaining the photo-degradation of DBP
      under acidic conditions. The use of 254 nm UV to photo-degrade DBP was found to
      be a relatively fast and clean process, especially in neutral to basic
      conditions.

PMID- 15993152
TI  - Cadmium ion sorption onto lignocellulosic biosorbent modified by sulfonation: the
      origin of sorption capacity improvement.
AB  - Juniper (Juniperus monosperma), a small-diameter underutilized material, has been
      studied as a lignocellulosic biosorbent for removing heavy metals from water. In
      this study, juniper wood was modified by sulfonation to enhance sorption capacity
      for cadmium in water. The origin of the enhancement was investigated by observing
      the sorption behaviors and the change in surface functional group concentrations.
      Cadmium sorption by all juniper wood biosorbents studied was fast and the
      sorption capacity decreased with decreasing pH, similar to results found for
      other biosorbents. Sulfonated juniper was found to have at least twice the
      sorption capacity for cadmium removal from water compared to that of untreated
      juniper, though the sorption capacity increased with increasing pH. A slight
      increase in carboxylate content after sulfonation was likely responsible for a
      small portion of the enhancement. Elemental analysis showed an increase in sulfur
      content after sulfonation. Diffuse reflectance infrared Fourier transform (DRIFT)
      spectra showed a decrease in the band at 1660 cm(-1) in the range of carbonyl
      groups as a result of sulfonation. This indicates that coniferaldehyde groups in
      the lignin of juniper wood corresponding to this band were substituted into
      sulfonic acid groups after sulfonation. This interpretation was supported by both
      the color forming reaction with phloroglucinol-hydrochloric acid and the reaction
      mechanisms from the acid sulfite pulping process. Consequently, the enhancement
      of cadmium sorption capacity of juniper wood by sulfonation mainly originated
      from the production of sulfonic acid groups, which are binding sites for heavy
      metals.

PMID- 15993153
TI  - The EDTA effect on phytoextraction of single and combined metals-contaminated
      soils using rainbow pink (Dianthus chinensis).
AB  - Rainbow pink (Dianthus chinensis), a potential phytoextraction plant, can
      accumulate high concentrations of Cd from metal-contaminated soils. The soils
      used in this study were artificially added with different metals including (1)
      CK: original soil, (2) Cd-treated soil: 10 mg Cd kg(-1), (3) Zn-treated soil: 100
      mg Zn kg(-1), (4) Pb-treated soil: 1000 mg Pb kg(-1), (5) Cd-Zn-treated soil: 10
      mg Cd kg(-1) and 100 mg Zn kg(-1), (6) Cd-Pb-treated soil: 10 mg Cd kg(-1) and
      1000 mg Pb kg(-1), (7) Zn-Pb-treated soil: 100 mg Zn kg(-1) and 1000 mg Pb kg(
      1), and (8) Cd-Zn-Pb-treated soil: 10 mg Cd kg(-1), 100 mg Zn kg(-1), and 1000 mg
      Pb kg(-1). Three concentrations of 2Na-EDTA solutions (0 (control), 2, and 5 mmol
      kg(-1) soil) were added to the different metals-treated soils to study the
      influence of applied EDTA on single and combined metals-contaminated soils
      phytoextraction using rainbow pink. The results showed that the Cd, Zn, Pb, Fe,
      or Mn concentrations in different metals-treated soil solutions significantly
      increased after applying 5 mmol EDTA kg(-1) (p<0.05). The metal concentrations in
      different metals-treated soils extracted by deionized water also significantly
      increased after applying 5 mmol EDTA kg(-1) (p<0.05). Because of the high
      extraction capacity of both 0.005 M DTPA (pH 5.3) and 0.05 M EDTA (pH 7.0),
      applying EDTA did not significantly increase the Cd, Zn, or Pb concentration in
      both extracts for most of the treatments. Applying EDTA solutions can
      significantly increase the Cd and Pb concentrations in the shoots of rainbow pink
      (p<0.05). However, this was not statistically significant for Zn because of the
      low Zn concentration added into the contaminated soils. The results from this
      study indicate that applying 5 mmol EDTA kg(-1) can significantly increase the
      Cd, Zn, or Pb concentrations both in the soil solution or extracted using
      deionized water in single or combined metals-contaminated soils, thus increasing
      the accumulated metals concentrations in rainbow pink shoots. The proposed method
      worked especially well for Pb (p<0.05). The application of 2 mmol EDTA kg(-1)
      might too low to enhance the phytoextraction effect when used in silty clay
      soils.

PMID- 15993154
TI  - Mineralization of dinitrotoluenes and trinitrotoluene of spent acid in toluene
      nitration process by Fenton oxidation.
AB  - Fenton's reagent, UV/H2O2 and UV/Fenton's reagent were employed to mineralize
      dinitrotoluene (DNT) isomers and 2,4,6-trinitrotoluene (TNT) of spent acid in
      toluene nitration process. The bench-scale experiments were conducted to
      elucidate the influence of various operating variables on the performance of
      removal of total organic compounds (TOC) from spent acid, including reaction
      temperature, concentration of ferrous ion and H2O2 dosage. It is remarkable that
      organic compounds were completely mineralized by Fenton oxidation, of which
      removal efficiency is superior to that of UV/H2O2. Nevertheless, it makes slight
      difference between Fenton oxidation and UV/Fenton oxidation. According to the
      spectra identified by gas chromatograph/mass spectrometer (GC/MS), it is proposed
      that oxidative degradation of DNT isomers leads to o-, m-, p-mononitrotoluene
      (MNT) and 1,3-dinitrobenzene respectively. Besides, the oxidation of 2,4,6-TNT
      gives the 1,3,5-trinitrobenzene intermediate. Apparently, Fenton oxidation is
      promising for purification of spent acid industrially.

PMID- 15993155
TI  - Selection of an electrolyte to enhance the electrochemical decolourisation of
      indigo. Optimisation and scale-up.
AB  - The investigation presented here focussed on the electrochemical decolourisation
      of a commercial, textile indigo dye, in an undivided electrochemical cell using
      graphite electrodes. The decolourisation values obtained employing halide salts-
      sodium chloride, potassium bromide and potassium iodide--and a reductive agent-
      sodium meta-bisulphite--as electrolytes are higher than those attained when no
      electrolyte was used. The highest decolourisation value at a low level of
      electric power consumption was obtained with sodium chloride. Besides, this
      electrolyte is usually found in the coloured wastewaters of textile industry.
      Thus, a detailed study was carried out to determine the influence of electrolyte-
      sodium chloride--and dye concentration on the efficiency of the process expressed
      in terms of energy consumption and extension of the decolourisation reaction. The
      scale-up of the treatment with sodium chloride was satisfactorily tested in a 20
      l cell.

PMID- 15993156
TI  - Bioleaching of metal from municipal waste incineration fly ash using a mixed
      culture of sulfur-oxidizing and iron-oxidizing bacteria.
AB  - We investigated the behavior and characteristics of metal leaching from municipal
      solid waste incineration (MSWI) fly ash among pure cultures of a sulfur-oxidizing
      bacterium (SOB) and an iron-oxidizing bacterium (IOB) and a mixed culture. The
      IOB has a high metal-leaching ability, though its tolerability against the ash
      addition is low. The SOB might better tolerate an increase in ash addition than
      the IOB, though metal leaching ability of the SOB is limited. Mixed culture could
      compensate for these deficiencies, and high metal leachability was exhibited in
      the 1% ash culture, i.e., 67% and 78% of leachabilities for Cu and Zn,
      respectively, and 100% for Cr and Cd. Furthermore, comparably high leachabilities
      such as 42% and 78% for Cu and Zn were observed even in the 3% ash cultures.
      Characterization of metal leaching by the mixed culture revealed that the acidic
      and oxidizing condition had remained stable thorough the experimental period.
      Ferric iron remained in the mixed culture, and the metal leaching was enhanced by
      redox mechanisms coupling with the leaching by sulfate. An increase of ferrous
      iron enhanced the Cr, Cu, and As leaching. The optimum concentration of sulfur
      existed for As and Cr (5 gl(-1)) and Cu (2 gl(-1)). The presence of the
      degradable and non-degradable organic compound that must be existed in the
      natural environment or waste landfills made no significant change in the
      leachability of metals other than Zn. These results suggested that bioleaching
      using a mixed culture of SOB and IOB is a promising technology for recovering the
      valuable metals from MSWI fly ash.

PMID- 15993157
TI  - Sorption of pentachlorophenol on pine bark.
AB  - The minimization of pentachlorophenol (PCP) transport in the environment driven
      by industrial wastewater discharges can be accomplished by sorption in natural,
      available and low cost by-products like pine bark. Taking into account that PCP
      is a chemical which behaviour is highly dominated by the surrounding features,
      this work intended to evaluate the sorption kinetics and equilibrium parameters
      according to the pH and temperature as well as the pine bark particle size. The
      PCP uptake by pine bark showed to be faster in the initial phase followed by a
      slower process, being 24 h the suitably time to reach the sorption equilibrium in
      the range of pH studied. The neutral PCP species showed to have higher binding
      capacity to pine bark than the anionic PCP, which was reflected in a decrease in
      the distribution coefficient (Kd) of the linear sorption isotherm with the
      increase of solution pH from 2 to 7. On the other hand, between 10 degrees C and
      35 degrees C, the temperature does not seem to play a significant role in the PCP
      sorption by pine bark, while the sorbent size is a key parameter to enhance the
      overall process.

PMID- 15993158
TI  - Photo-Fenton-assisted ozonation of p-Coumaric acid in aqueous solution.
AB  - The degradation of p-Coumaric acid present in olive oil mill wastewater was
      investigated as a pretreatment stage to obtain more easily biodegradable
      molecules, with lower toxicity that facilitates subsequent anaerobic digestion.
      Thus, photo-Fenton-assisted ozonation has been studied and compared with
      ozonation at alkaline pH and conventional single ultraviolet (UV) and acid
      ozonation treatments. In the combined process, the overall kinetic rate constant
      was split into various components: direct oxidation by UV light, direct oxidation
      by ozone and oxidation by hydroxyl radicals. Molecular and/or radical ozone
      reaction was studied by conducting the reaction in the presence and absence of
      tert-butylalcohol at pHs 2, 7 and 9. Ozone oxidation rate increases with pH or by
      the addition of Fenton reagent and/or UV radiation due to generation of hydroxyl
      radicals, *OH. Hydrogen peroxide and ferrous ion play a double role during
      oxidation since at low concentrations they act as initiators of hydroxyl radicals
      but at high concentrations they act as radical scavengers. Finally, the
      additional levels of degradation by formation of hydroxyl radicals have been
      quantified in comparison to the conventional single processes and an equation is
      proposed for the reaction rate as a function of studied operating variables.

PMID- 15993159
TI  - Use of ozone and/or UV in the treatment of effluents from board paper industry.
AB  - The aim of this work has been to study the viability of ozone and/or UV in the
      treatment of cardboard industry effluents. Several model compounds have been
      chosen for the experiments: guaicol, eugenol, glucose, acetate and butyrate.
      Significant differences in the ozonisation rates are observed between phenolic
      products coming from lignin (eugenol and guaiacol) and aliphatic compounds.
      Reactions fit in all cases a pseudo-first order kinetics and are influenced by
      the pH of the solution. Real effluents have also been tested, and the COD
      decrease has been found to depend on the fatty acids/phenols ratio. Finally,
      respirometric studies have shown an increase in the BODst in effluents subjected
      to a mild oxidation, while under stronger conditions a BODst decrease is
      observed.

PMID- 15993160
TI  - Efficient use of Fe metal as an electron transfer agent in a heterogeneous Fenton
      system based on Fe0/Fe3O4 composites.
AB  - In this work a novel heterogeneous Fenton system based on Fe(0)/Fe3O4 composites
      is described. The composites with several Fe(0)/Fe3O4 ratios were prepared by two
      different methods, i.e. mechanical alloying of Fe(0) and Fe3O4 powders and
      controlled reduction of Fe3O4 with H2. Reaction studies and detailed Conversion
      Electron Mossbauer surface characterization of the composites Fe(0)/Fe3O4, Fe(0),
      Fe3O4, alpha-Fe2O3 and gamma-Fe2O3 suggested that Fe2+surf species are essential
      to produce an active Fenton system. Kinetic studies for the oxidation of the dye
      methylene blue, used as an organic model molecule, and for the peroxide
      decomposition suggest that the reactions proceed via HO* radicals generated from
      Fe2+surf species and H2O2 in a Fenton like mechanism. The increase in activity
      caused by the addition of Fe(0) is discussed in terms of a creation of Fe2+surf
      species during the preparation of the composite and by an electron transfer
      mechanism from Fe(0) to Fe3+surf during the Fenton reaction to regenerate the
      Fe2+surf active species.

PMID- 15993161
TI  - Inhibition of laccase activity from Trametes versicolor by heavy metals and
      organic compounds.
AB  - Due to the numerous biotechnological applications of laccase enzyme, it is
      essential to know the influence of different agents usually present in the
      natural environment on its enzymatic action, especially for in situ treatment
      technologies. In the present work, a simple and rapid method to determine the
      inhibitory or inducer effect of different compounds on laccase activity was
      developed. The compounds tested were copper-chelating agents and heavy metals. It
      was found that using syringaldazine as a substrate, all copper-chelating agents
      (except EDTA) highly inhibited laccase activity (around 100%) at an inhibitor
      concentration lower than 20 mM. Moreover, 40% of inhibition, which was detected
      at a concentration of 20 mM for both Cd(2+) and Cu(2+) increased with
      concentration until nearly complete inhibition at 80 mM.

PMID- 15993162
TI  - Roles of physical and chemical properties of activated carbon in the adsorption
      of lead ions.
AB  - Elucidation of the roles of chemical and physical properties of activated carbons
      is an important basis for the systematic development of adsorbents with optimal
      properties specific for certain applications. Such an understanding has
      challenged most researchers and this has been attributed with the difficulty in
      decoupling the effect of chemical and physical properties that characterize
      activated carbons. This study proposed empirical modeling in resolving the
      effects of individual carbon properties in lead adsorption. A model based on lead
      adsorption and carbon properties including total surface area, mean pore size and
      heteroatom concentrations has been shown to adequately describe the lead
      adsorption onto activated carbons prepared from bagasse. To support this
      investigation a series of activated carbons were prepared from bagasse by
      physical and by chemical activation techniques. The surface chemical properties
      of the carbons were inferred from carbon pH and heteroatom concentrations. The
      physical characterizations of the carbons included total surface area by the BET
      technique and mean pore size measured using the Horvath-Kawazoe equation.
      Adsorption tests were conducted using a low concentration of lead (5 ppm) and the
      solution pH was maintained at 1.0 to maintain lead speciation to the un-complexed
      Pb(2+) ion. The adequacy of the proposed empirical models was statistically
      assessed. This form of analysis was shown to provide valuable information in
      tailor making adsorbents and selecting appropriate adsorbents for lead
      adsorption.

PMID- 15993163
TI  - Sorption of cadmium, copper, and zinc ions onto bone char using Crank diffusion
      model.
AB  - The rates of adsorption of cadmium, copper and zinc ions onto bone char have been
      studied in three single component systems using an agitated batch adsorber. The
      effects of initial metal ion solution concentration and bone char mass have been
      studied. The capacities of the three metals on bone char are 0.477, 0.709 and
      0.505 mmol g(-1) for cadmium, copper and zinc respectively which are much higher
      than most other adsorbents reported in the literature for these three metals. In
      order to model the experimental concentration decay curves, a film-surface
      diffusion equation proposed by has been solved. The model results correlate the
      experimental better than a previously applied film-pore diffusion model. However,
      the results indicate that the surface diffusion coefficient was a variable
      function of initial metal ion concentration. The surface diffusivities vary from
      3.00 x 10(-9) to 8.80 x 10(-9) cm(2)s(-1), 2.11 x 10(-9) cm(2)s(-1) to 5.4 x 10(
      9) cm(2)s(-1) and 3.10 x 10(-9) to 8.49 x 10(-9) cm(2)s(-1) for cadmium, copper
      and zinc respectively, for metal ion solution concentrations of 2.10-5.40 mmol
      dm(-3).

PMID- 15993164
TI  - Direct Yellow and Methylene Blue liquid-liquid extraction with alkylene
      carbonates.
AB  - Propylene and 1,2-butylene carbonates enable very effective extraction of
      Methylene Blue. The use of a more hydrophobic 1,2-butylene carbonate is preferred
      for practical application. Separation is enhanced by addition of an electrolyte
      (NaCl). Partition coefficients for solutions containing Methylene Blue and 1M
      NaCl are at least a hundred times higher than for Direct Yellow solutions. The
      recovery of Methylene Blue with propylene and 1,2-butylene carbonates is
      significantly better, compared with the cloud point technique. Cloud point
      technique yields to almost 100% only in the case of low concentrations of
      Methylene Blue in the feed (0.5mg dm(-3)). For higher initial concentrations
      (0.01-0.25 g dm(-3)) of Methylene Blue, this method of recovery provides low
      extraction percentages (10-40%). Alkylene carbonates are not appropriate
      extractants for recovery of very hydrophilic Direct Yellow.

PMID- 15993165
TI  - Lead electrocapture on hydroxyapatite coated electrodes.
AB  - Hydroxyapatite coated electrodes were made by a hydrolysis reaction involving
      silanes and hydroxyapatite particles on stainless steel. Aqueous lead ions were
      captured on the coatings with or without electromigration. Results depend on
      coating thickness, supporting electrolyte and the presence of the electric field.
      It was found that this new electrocapture method can remove lead from solutions
      down to ppb levels.

PMID- 15993166
TI  - Degradation of trichloroethylene by photocatalysis in an internally circulating
      slurry bubble column reactor.
AB  - The effects of initial trichloroethylene (TCE) concentration, recirculating
      liquid flow rate and gas velocity on photodegradation of TCE have been determined
      in an internally circulating slurry bubble column reactor (0.15m-ID x 0.85 m
      high). Titanium dioxide (TiO2) powder was employed as a photocatalyst and the
      optimum loading of TiO2 in the present system is found to be approximately 0.2
      wt%. The stripping fraction of TCE by air flow increases but photodegradation
      fraction of TCE decreases with increasing the initial TCE concentration,
      recirculating liquid flow rate and gas velocity. The average removal efficiency
      of TCE is found to be approximately 97% in an internally circulating slurry
      bubble column reactor.

PMID- 15993169
TI  - Reversal of cerebral vasospasm by sphenopalatine ganglion stimulation in a dog
      model of subarachnoid hemorrhage.
AB  - BACKGROUND: Sphenopalatine ganglion stimulation dilates the ipsilateral arteries
      of the normal dog anterior circle of Willis. This experiment tested whether
      similar stimulation would reverse cerebral vasospasm. METHODS: Six dogs underwent
      baseline angiography followed by creation of subarachnoid hemorrhage (SAH) by
      injection of autologous blood into the cisterna magna. Two days later,
      subarachnoid blood injection was repeated. Seven days later, angiography was
      repeated and the left sphenopalatine ganglion was exposed microsurgically.
      Angiography was repeated 15 minutes after exposure of the ganglion. The ganglion
      was then stimulated electrically 3 times and angiography repeated during, and 15
      and 30 minutes after stimulation. The protocol was repeated again. Adequacy of
      stimulation was confirmed by the presence of immediate ipsilateral nasal mucus
      production. RESULTS: Subarachnoid hemorrhage was associated with significant
      vasospasm of both middle cerebral arteries (11% +/- 4% and 18% +/- 7%, P < .05,
      paired t tests). Exposure of the ganglion and sham stimulation produced no
      substantial changes in arterial diameters compared with the diameter before
      stimulation and after ganglion exposure (n = 2-6 per measurement, paired t
      tests). Ganglion stimulation produced significant dilatation of the ipsilateral
      extracranial and intracranial internal carotid, middle cerebral, and anterior
      cerebral arteries compared with the contralateral arteries (13% +/- 6% to 32% +/-
      14%, P < .05, paired t tests). CONCLUSIONS: The mild to moderate vasospasm that
      results from SAH in dogs was reversed by sphenopalatine ganglion stimulation.
      Since this method carries a potential for human application, additional studies
      are warranted to determine the effects on more severe vasospasm.

PMID- 15993171
TI  - Complications of endovascular treatment of cerebral aneurysms.
AB  - BACKGROUND: The International Subarachnoid Aneurysm Trial has indicated that
      endovascular management of acutely ruptured aneurysms may be superior to surgery.
      Clearly poor results ensue from both forms of treatment, and some of these are
      because of technical complications (not just poor patient status). This
      observational study was performed to determine the complications associated with
      the endovascular treatment of ruptured and unruptured cerebral aneurysms.
      METHODS: Prospective data were gathered on 118 patients undergoing 126
      endovascular treatment sessions for 126 nontraumatic cerebral aneurysms (30%
      unruptured) over a 3-year period. The average age was 51 years (range, 12-85
      years). Females comprised 75% of the population treated. RESULTS: Good outcomes
      were achieved with 71% of the procedures (59% for subarachnoid hemorrhage [SAH];
      97% for unruptured). No bleeding or rebleeding occurred from treated aneurysms.
      Vessel or aneurysm perforation occurred in 11 cases and led to adverse outcome in
      3 (3%). Thromboembolic complications were felt to cause cerebral infarction in 8
      cases (6%). The risk of vessel/aneurysm rupture or thromboembolic stroke was
      greater in patients with SAH. Eight attempts to coil (6%) were initially
      unsuccessful. Two of these were later successfully coiled and others had surgery.
      None of the failed attempts led to clinical deterioration. Balloon-assisted
      coiling (BAC) was not associated with an increased complication rate.
      CONCLUSIONS: Vessel perforation and thromboembolic stroke are significant risks
      of endovascular treatment, especially after SAH. In our hands, however, BAC does
      not add to this risk.

PMID- 15993174
TI  - Functional magnetic resonance imaging-guided resection of low-grade gliomas.
AB  - BACKGROUND: We sought to determine the safety and efficacy of using functional
      magnetic resonance imaging (fMRI) to guide the resection of low-grade gliomas
      (LGG). METHODS: From September 1997 to February 2003, fMRI was performed in 16
      patients (age, 15-43 years) before an attempted surgical resection of LGG.
      Functional imaging was used to identify and coregister eloquent cortices
      pertinent to motor (10), speech (3), motor and speech (2), and short-term memory
      and speech (1) activation with respect to the tumor using a 1.5-T interventional
      MRI system. Intraoperatively acquired T(2)-weighted and turbo-fluid attenuated
      inversion recovery images were used to assess the completeness of surgical
      resection. RESULTS: Tumors included 10 oligodendrogliomas, 4 astrocytomas, 1
      dysembryoplastic neuroepithelial tumor, and 1 pleomorphic xanthoastrocytoma. In
      every case, the preoperative brain activation study accurately determined the
      location of neurologic function. After surgery, one patient had a transient
      hemiparesis and another had a temporary apraxia. Ten patients had
      radiographically complete resections and 5 with oligodendrogliomas had incomplete
      resections because of the proximity of their tumors to functional areas. Only one
      patient with an astrocytoma in the motor strip received postoperative radiation
      therapy. To date, radiographic tumor progression has not been seen in any patient
      with either a partial or a complete resection with a median follow-up of 25
      months (range, 12-87 months). CONCLUSIONS: Functional MRI was accurate for
      identifying areas of neurologic function before surgical resection of LGG.
      Patients with complete radiographic resections or with incompletely resected
      oligodendrogliomas can be safely followed radiographically after surgery.
      Radiation therapy was reserved for infiltrating astrocytomas that were not
      completely resectable.

PMID- 15993176
TI  - Recurrent primary intracerebral hemorrhage in Izumo City, Japan.
AB  - BACKGROUND: Recurrent intracerebral hemorrhage (ICH) is a devastating illness
      among stroke survivors. We investigated the rate and characteristics of ICH
      recurrence in Izumo City, Japan. METHODS: The recurrence rate of ICH was
      calculated for 279 patients who suffered their first-ever ICH between 1991 and
      1998 and were followed up during a mean period of 3.0 years (range, 1 month to 11
      years). The characteristics of recurrent ICH were evaluated for 42 patients who
      were treated for it between 1991 and 1998. RESULTS: Of the 279 patients with ICH,
      19 (7%) had rebleeding; the recurrence rate was 2.3% per year. Analysis of the 42
      patients with recurrent ICH showed that the most common pattern of recurrence was
      ganglionic-ganglionic (n = 25). The crude and the age- and sex-adjusted annual
      incidence rates for recurrent ICH were both 6 per 100,000 population. Of the 42
      patients with recurrent ICH, 16 (38%) had a favorable outcome at discharge and 10
      (24%) died. The overall 1-year survival rate for recurrent ICH was 72%.
      Intraventricular hemorrhage on computed tomography scans was the only significant
      predictor of not only ICH recurrence but also the 1-year case-fatality rate in
      patients with recurrent ICH. CONCLUSIONS: Recurrence after an initial ICH is not
      rare, and the most common pattern of recurrence is ganglionic-ganglionic. Whereas
      the functional outcome of recurrent ICH is unsatisfactory, the 1-year survival
      rate is not necessarily low. Intraventricular hemorrhage on computed tomography
      scans is an important predictor of both ICH recurrence and the 1-year case
      fatality rate in patients with recurrent ICH.

PMID- 15993178
TI  - Sphenoid wing meningiomas with osseous involvement.
AB  - BACKGROUND: Sphenoid wing meningiomas (SWMs) with osseous involvement are
      neurosurgically challenging because of their position within the skull base and
      their high rates of recurrence. Sufficient resection of these meningiomas
      requires extensive surgical exposure. We report on 82 patients with meningiomas
      infiltrating the sphenoid wing, analyzing radiological appearance and its
      influence on surgical management. METHODS: Charts of the patients including
      surgical records, clinical reports, histological examinations, imaging studies,
      and meticulously focusing questionnaires were reviewed. RESULTS: Among the 82
      patients with osseous-involved SWMs, the mean age was 52.2 years in the female
      group and 54.7 years in the male group with a mean follow-up of 66.23 months (24
      206). Histological evaluation revealed World Health Organization grade I
      meningiomas in 94% of case patients, tumor infiltration of examined bone in all
      case patients, and proliferation rates of 2.2% Ki-67. Magnetic resonance imaging
      appearance of the SWMs demonstrated various densities as well as Gd enhancement
      within the affected bone. Recurrence rates in this subgroup of SWMs are higher
      (>30%) compared with meningiomas without osseous involvement (11.6%). CONCLUSION:
      Osseous involvement in SWMs accounts for lower resection and higher recurrence
      rates than meningiomas in other locations. In those cases with involvement of the
      cavernous sinus, a subtotal but extensive removal combined with bony
      decompression of the cranial nerves at the superior orbital fissure and optic
      canal frequently produces good functional and cosmetic results.

PMID- 15993180
TI  - Frontal skull base surgery combined with endonasal endoscopic sinus surgery.
AB  - BACKGROUND: Postoperative infection remains a serious complication after radical
      resection of anterior skull base lesions because intracranial, nasal, and
      paranasal cavities are opened during surgery. To prevent complications from
      postoperative infection, we combined endonasal endoscopic sinus surgery (ESS)
      with the frontal transbasal approach in patients with skull base lesions.
      METHODS: Patients (n = 16) with anterior skull base lesions extending to the
      paranasal or nasal cavity underwent surgical resection via the frontal transbasal
      approach. After removal of the lesion via the transcranial approach, enlargement
      of the ostium or sinusotomy was performed bilaterally using our endonasal ESS
      procedure. The main purpose of ESS is the establishment of a wide drainage route
      to avoid dead space and postoperative infection. Furthermore, we confirmed the
      absence of residual lesion and leakage of cerebrospinal fluid (CSF),
      endoscopically. RESULTS: The frontal transbasal approach combined with endonasal
      ESS was performed in 16 patients with frontal skull base lesions. There were 8
      malignant tumors, 6 benign tumors, and 2 mucoceles. Although 11 patients had
      preoperative active paranasal sinusitis, most frequently at the ethmoid sinus,
      none experienced postoperative infection. There was no complication related to
      ESS procedure. Furthermore, leakage of CSF and extracranial residual tumor were
      not found. CONCLUSION: Endonasal ESS after frontal skull base surgery is a highly
      useful technique for preventing postoperative infection, especially for the cases
      with large skull base tumors extending into other regions involving the paranasal
      sinuses or nasal cavity and with active paranasal sinusitis.

PMID- 15993182
TI  - Resection of arteriovenous malformation in the middle cerebellar peduncle by a
      posterior transpetrosal approach: illustration of a case and correlative
      microsurgical anatomy.
AB  - BACKGROUND: Lesions located in the posterolateral brain stem, particularly the
      middle cerebellar peduncle, have presented surgeons with a challenge associated
      with significant morbidity. METHODS: We present a case of a 20-year-old woman who
      had a hematoma in the right middle cerebellar peduncle with a ventricular
      rupture. Angiography revealed an arteriovenous malformation (AVM) located in the
      same portion, extending from the lateral surface near the entry zone of the
      trigeminal nerve to the paraventricular area of the fourth ventricle, which was
      completely resected through a posterior transpetrosal approach. We also describe
      the microsurgical anatomy of this region in a cadaveric specimen, presenting the
      anatomic landscape at the target when approaching through this route. RESULTS:
      The patient's postoperative course was uneventful and her neurologic deficits
      progressively but gradually improved. When a lesion exists at or close to the
      surface of the middle cerebellar peduncle, the best approach, in our estimation,
      is a transpetrosal approach because the lesion can be approached perpendicularly
      with a short working distance, various angles for dissection are available, and
      minimal retraction of the temporal lobe and cerebellum is required. CONCLUSION:
      An AVM embedded in the middle cerebellar peduncle can be successfully resected
      using a posterior transpetrosal approach, though we concede this approach is
      slightly labor-intensive and time-consuming.

PMID- 15993184
TI  - Papillary endothelial hyperplasia (Masson tumor) of the petrous and jugulare
      region: case report and literature review.
AB  - OBJECTIVE: Intracranial papillary endothelial hyperplasia (PEH) is rare, and only
      13 cases have been reported intracranially in the literature. In this article, we
      present a case of PEH involving petrous and jugular foramen region due to the
      uncommon incidence. CASE DESCRIPTION: A 49-year-old female patient with a 4-year
      history of left-sided hearing loss and facial palsy. Magnetic resonance (MR)
      imaging disclosed the presence of a 6 x 6 x 5 cm lobular mass occupying the left
      petrous and jugulare region. This mass was hyperintense on both T1 and T2
      weighted MR images and was enhanced strongly with gadolinium. No edema was found
      around the lesion. Preoperative digital subtraction angiogram examination showed
      that the lesion had a rich blood supply. Therefore, polyvinyl alcohol
      embolization was carried out to reduce bleeding during operation. A left-sided
      suboccipital extreme lateral approach was applied for craniotomy. The lesion was
      extradural and highly vascular with extension into the petrous bone. It was
      subtotally removed. Postoperative course of the patient was stable. Her
      neurologic evaluation was the same as preoperatively. CONCLUSION: Surgical
      excision of the lesion is the main therapy. Radiotherapy should be given to
      patients whose lesion cannot be totally removed.

PMID- 15993186
TI  - Clinical relevance of hydrocephalus in bacterial meningitis in adults.
AB  - BACKGROUND: The predictive factors, clinical relevance, and outcomes of
      hydrocephalus complicating adult bacterial meningitis were studied. METHODS: In
      this 16-year retrospective study, 136 adult patients were identified with culture
      proven bacterial meningitis. A comparison was made between the clinical and
      cerebrospinal fluid data of patients with and without hydrocephalus on admission.
      RESULTS: Twenty-eight patients had hydrocephalus secondary to bacterial
      meningitis, accounting for 21% (28/136) of the episodes. Of the 28 patients, the
      initial computed tomographic scans and/or magnetic resonance imaging studies
      revealed hydrocephalus in 27 patients, and delayed hydrocephalus developed
      despite commencement of antimicrobial therapy in the remaining patient. The
      interval from initial symptoms to external ventricular drainage was 3.9 +/- 4.6
      days (range, 1-14 days). Among them, 7 patients underwent external ventricular
      drainage for hydrocephalus during the acute phase of bacterial meningitis. At
      follow-up of at least 6 months or more, 14 patients survived and 14 died, with an
      overall mortality rate of 50%. CONCLUSION: In this study, disturbed consciousness
      and a higher mean age at the time of admission are risk factors for developing
      hydrocephalus during the acute phase of bacterial meningitis. Poor outcomes are
      also found in this specific group of patients, and these may be attributed to the
      infection itself, hydrocephalus, or both. Because of fulminated clinical courses
      and high fatality rates, surgical intervention may be suitable only for those who
      have progressive hydrocephalus and are neurologically stable. In spite the high
      fatality rate, adequate treatment of neurologic complications and aggressive
      antimicrobial therapy are essential in improving therapeutic outcomes.

PMID- 15993188
TI  - Delayed cranial neuropathy after neurosurgery caused by herpes simplex virus
      reactivation: report of three cases.
AB  - BACKGROUND: Delayed cranial neuropathy is an uncommon complication of
      neurosurgical interventions of which the exact etiology is uncertain. Several
      authors have hypothesized that reactivation of herpesviruses may play a role.
      CASE DESCRIPTIONS: The first patient underwent microvascular decompression of the
      left facial nerve because of hemifacial spasm. Nine days postoperatively, he
      developed severe facial weakness on the ipsilateral side. The polymerase chain
      reaction for herpes simplex virus (HSV) was positive in the cerebrospinal fluid
      (CSF). Treatment with intravenous acyclovir was initiated, after which a rapid
      and marked improvement was observed. The second patient developed left-sided
      facial numbness 20 days after microvascular decompression of the left facial
      nerve. The polymerase chain reaction for HSV was positive in the CSF. Treatment
      with intravenous acyclovir resulted in full recovery. The third patient underwent
      a suboccipital craniectomy with excision of a meningioma located at the left
      petrosal apex. Three months postoperatively, she developed multiple cranial
      neuropathies (involving cranial nerves V, VI, VIII, and XII). This was
      accompanied by serologic evidence of HSV reactivation and a positive polymerase
      chain reaction for HSV in the CSF. The patient was successfully treated with
      intravenous acyclovir. CONCLUSIONS: The 3 reported cases provide evidence that
      delayed postoperative cranial neuropathy can be caused by HSV reactivation and
      can involve multiple cranial nerves. An increased awareness of this treatable
      postoperative complication is warranted.

PMID- 15993191
TI  - Transconjunctival approach for retrobulbar intraconal orbital cavernous
      hemangiomas. Orbital surgeon's perspective.
AB  - BACKGROUND: Cavernous hemangioma is the most common benign intraorbital tumor
      found in adults. Most cavernous hemangiomas are located within the intraconal
      space. When indicated, complete surgical removal is the only treatment option.
      Several surgical techniques have been refined over the past decades. We describe
      our experience over transconjunctival approach in 24 patients with retrobulbar
      intraconal orbital cavernous hemangiomas. METHOD: This retrospective study
      includes 24 nonrandomly selected patients who had retrobulbar intraconal tumors.
      The presumptive preoperative diagnosis was based on magnetic resonance imaging
      findings. Compression on the optic nerve and/or the globe and proptosis
      constituted indications for surgery. The tumor was exposed via a
      transconjunctival route after temporarily disinserting an extraocular muscle
      depending on the location of the lesion. RESULTS: In all patients, the tumor was
      in touch with the globe and in most cases extended to the orbital apex. All
      tumors were removed intact. In 14 patients, tumors were extirpated with the aid
      of a cryoprobe. Visual acuity increased in 8 patients and remained stable in the
      rest. No serious or permanent complications were observed during or after the
      operation. CONCLUSIONS: Retrobulbar intraconal cavernous hemangiomas can be
      removed successfully through a transconjunctival approach with minimal damage to
      surrounding tissues. This method is best for tumors whose anterior borders are in
      contact or very close to the eye even if the posterior border abuts the orbital
      apex.

PMID- 15993192
TI  - The Oxiplex/SP gel-morphine compound after lumbar microdiscectomy in the
      management of postoperative pain. Report of 20 cases.
AB  - OBJECT: Morphine-based compounds are used epidurally after lumbar microdiscectomy
      to minimize postoperative pain. After the withdrawal of ADCON-L we started to use
      Oxiplex (Oxiplex/SP Gel) as a barrier against epidural fibrosis and as a vehicle
      for morphine delivery. METHODS: We administered epidurally morphine (1 mg)
      dissolved in Oxiplex gel to 20 consecutive patients after lumbar microdiscectomy,
      evaluating safety and analgesic effectiveness. Outcome measures adopted were (1)
      visual analog scale (VAS) of back and radicular pain, (2) straight leg raising
      (SLR) maneuver to assess evoked pain, (3) postoperative time to comfortable
      ambulation, (4) postoperative hospitalization, (5) postoperative request of
      analgesics, and (6) postoperative work time loss. RESULTS: No complications, such
      as urinary retention, respiratory disturbances, or wound infections, were
      observed. During the first 24 hours the mean VAS was lower than the preoperative
      one (12.5 vs 77.3 mm, respectively; P < .01). The mean postoperative SLR was
      62.25 degrees vs 38.74 degrees of preoperative period (P < .05). After a mean of
      29.8 hours, patients were discharged. Twelve patients (60%) had low back and
      radicular pain relapse 36 to 72 hours after operation, requiring assumption of
      analgesics. At that time, 2 patients reported a level of pain higher than the
      preoperative one. At 1- and 2-week follow-up visits, mean VAS scores were 33.5
      and 12.0 mm, respectively. The 2-week overall treatment satisfaction rating was
      excellent for 60% and good for 40%. Finally, the mean postoperative work time
      loss was 27 days. CONCLUSIONS: The epidural application of Oxiplex-morphine
      compound after lumbar microdiscectomy was found to be safe. Regarding
      postoperative pain control, it was found to be effective only during the first 36
      hours.

PMID- 15993195
TI  - Cervicothoracolumbar pneumorachis. Case report and review of the literature.
AB  - BACKGROUND: Pneumorachis is a very rare entity to occur after a major trauma. It
      is even rarer when its occurrence is not associated with injuries in the skull
      base, chest, abdomen, pelvis, or spine. Pneumorachis extending through the entire
      spinal canal has never been reported. CASE DESCRIPTION: We report a case of
      traumatic air penetration into the spinal canal in a patient, involved in a road
      traffic accident, who had no apparent major bone and soft tissue injuries. The
      patient was conscious (Glasgow Coma Scale score of 15/15) upon admission. A
      cervical lateral x-ray taken the day after admission showed some air in the
      spinal canal. A subsequent computed tomography with reconstruction disclosed some
      subdural air extending from the cervical region to the lumbar region. The patient
      was successfully treated conservatively. The pathogenesis and rarity of this
      pathology are discussed along with the review of relevant literature. CONCLUSION:
      Any patient with spinal pneumorachis should be actively investigated to determine
      if a possible air fistula, which might increase causing spinal cord compression,
      is present. If a source is not found, a skull base fracture should be suspected.

PMID- 15993196
TI  - Cervicothoracic spinal epidural cavernous hemangioma: case report and review of
      the literature.
AB  - Cavernous hemangiomas are vascular malformations that effect the central nervous
      system. This pathology is frequently encountered in the cerebral hemispheres,
      cerebellum, and brainstem. Cavernous hemangiomas, although usually solitary, may
      be associated with the same lesion in other parts of the central nervous system
      or other organ systems and may appear as sporadic or familial cases. They are
      infrequently found at the spinal level; in particular, pure cervicothoracic
      epidural location is rare. We report a case with a purely spinal epidural
      cavernous hemangioma from C6 to T1 and discuss the clinical, diagnostic, and
      therapeutic aspect of this unusual spinal malformation.

PMID- 15993198
TI  - Rapid expansion of a ventral arachnoid cyst after syringo-subarachnoid shunting
      in the thoracic spinal cord: case report.
AB  - BACKGROUND: Intradural spinal arachnoid cysts have rarely been reported in
      association with intramedullary cysts. These associated lesions most commonly
      occur in the thoracic spine. CASE DESCRIPTION: We reported an unusual balance of
      cerebrospinal fluid dynamics between an initially occult arachnoid cyst and
      syringomyelia. The arachnoid cyst was not allowed to express itself until the
      syrinx was decompressed with a syringo-subarachnoid shunt. CONCLUSION: Only one
      other report in the literature described a similar case; however, our case is the
      first to be confirmed by intraoperative ultrasound.

PMID- 15993199
TI  - The high price of innovation.

PMID- 15993204
TI  - Trends in neurosurgery in the United States.

PMID- 15993205
TI  - Re: Endoscopic third ventriculostomy for chronic hydrocephalus after tuberculous
      meningitis [Jonathan A, Rajshekhar V. Surg Neurol 63 (2005) 32-35].

PMID- 15993207
TI  - Percutaneous vertebroplasty for treatment of thoracolumbar spine bursting
      fracture. Chen JF, Lee ST. Surg Neurol 2004;62:494-500.

PMID- 15993209
TI  - In defence of Roy Meadow.

PMID- 15993210
TI  - Conjunctivitis in children.

PMID- 15993211
TI  - The value of cholera vaccines reassessed.

PMID- 15993212
TI  - Juvenile idiopathic arthritis and HSP60 vaccination: selective down-regulation?

PMID- 15993213
TI  - Indigenous peoples' health--why are they behind everyone, everywhere?

PMID- 15993214
TI  - Literature searches: look before you leap.

PMID- 15993215
TI  - Fatigue.

PMID- 15993217
TI  - UK doctors' morale.

PMID- 15993218
TI  - UK doctors' morale.

PMID- 15993219
TI  - UK doctors' morale.

PMID- 15993220
TI  - UK doctors' morale.

PMID- 15993221
TI  - Sample size and the ethics of non-inferiority trials.

PMID- 15993222
TI  - Hypertension--time to move on.

PMID- 15993223
TI  - Why is income inequality linked to altruism?

PMID- 15993224
TI  - Is disease causation random?

PMID- 15993225
TI  - Peacebuilding through health in Israel and Palestine.

PMID- 15993226
TI  - Live organ-donation for islet transplantation.

PMID- 15993227
TI  - Development and effects of a neonatal care unit in rural India.

PMID- 15993228
TI  - Another swollen calf.

PMID- 15993229
TI  - RIP medical profession?

PMID- 15993230
TI  - A simple score (ABCD) to identify individuals at high early risk of stroke after
      transient ischaemic attack.
AB  - BACKGROUND: Effective early management of patients with transient ischaemic
      attacks (TIA) is undermined by an inability to predict who is at highest early
      risk of stroke. METHODS: We derived a score for 7-day risk of stroke in a
      population-based cohort of patients (n=209) with a probable or definite TIA
      (Oxfordshire Community Stroke Project; OCSP), and validated the score in a
      similar population-based cohort (Oxford Vascular Study; OXVASC, n=190). We
      assessed likely clinical usefulness to front-line health services by using the
      score to stratify all patients with suspected TIA referred to OXVASC (n=378,
      outcome: 7-day risk of stroke) and to a hospital-based weekly TIA clinic (n=210;
      outcome: risk of stroke before appointment). RESULTS: A six-point score derived
      in the OCSP (age [> or =60 years=1], blood pressure [systolic >140 mm Hg and/or
      diastolic > or =90 mm Hg=1], clinical features [unilateral weakness=2, speech
      disturbance without weakness=1, other=0], and duration of symptoms in min [> or
      =60=2, 10-59=1, <10=0]; ABCD) was highly predictive of 7-day risk of stroke in
      OXVASC patients with probable or definite TIA (p<0.0001), in the OXVASC
      population-based cohort of all referrals with suspected TIA (p<0.0001), and in
      the hospital-based weekly TIA clinic-referred cohort (p=0.006). In the OXVASC
      suspected TIA cohort, 19 of 20 (95%) strokes occurred in 101 (27%) patients with
      a score of 5 or greater: 7-day risk was 0.4% (95% CI 0-1.1) in 274 (73%) patients
      with a score less than 5, 12.1% (4.2-20.0) in 66 (18%) with a score of 5, and
      31.4% (16.0-46.8) in 35 (9%) with a score of 6. In the hospital-referred clinic
      cohort, 14 (7.5%) patients had a stroke before their scheduled appointment, all
      with a score of 4 or greater. CONCLUSIONS: Risk of stroke during the 7 days after
      TIA seems to be highly predictable. Although further validations and refinements
      are needed, the ABCD score can be used in routine clinical practice to identify
      high-risk individuals who need emergency investigation and treatment.

PMID- 15993231
TI  - Chloramphenicol treatment for acute infective conjunctivitis in children in
      primary care: a randomised double-blind placebo-controlled trial.
AB  - BACKGROUND: One in eight schoolchildren have an episode of acute infective
      conjunctivitis every year. Standard clinical practice is to prescribe a topical
      antibiotic, although the evidence to support this practice is scarce. We
      undertook a randomised double-blind trial to compare the effectiveness of
      chloramphenicol eye drops with placebo in children with infective conjunctivitis
      in primary care. METHODS: Our study included 326 children aged 6 months to 12
      years with a clinical diagnosis of conjunctivitis who were recruited from 12
      general medical practices in the UK. We assigned 163 children to receive
      chloramphenicol eye drops and 163 to receive placebo eye drops. Eye swabs were
      taken for bacterial and viral analysis. The primary outcome was clinical cure at
      day 7, which was assessed from diaries completed by parents. All children were
      followed up for 6 weeks to identify relapse. Survival statistics were used for
      comparison, and analysis was by intention to treat. FINDINGS: Nine children were
      lost to follow-up (one in chloramphenicol group; eight in placebo group).
      Clinical cure by day 7 occurred in 128 (83%) of 155 children with placebo
      compared with 140 (86%) of 162 with chloramphenicol (risk difference 3.8%, 95% CI
      -4.1% to 11.8%). Seven (4%) children with chloramphenicol and five (3%) with
      placebo had further conjunctivitis episodes within 6 weeks (1.2%, -2.9% to 5.3%).
      Adverse events were rare and evenly distributed between each group.
      INTERPRETATION: Most children presenting with acute infective conjunctivitis in
      primary care will get better by themselves and do not need treatment with an
      antibiotic.

PMID- 15993232
TI  - Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a
      reanalysis.
AB  - BACKGROUND: Decisions about the use of killed oral cholera vaccines, which confer
      moderate levels of direct protection to vaccinees, can depend on whether the
      vaccines also provide indirect (herd) protection when high levels of vaccine
      coverage are attained. We reanalysed data from a field trial in Bangladesh to
      ascertain whether there is evidence of indirect protection from killed oral
      cholera vaccines. METHODS: We analysed the first year of surveillance data from a
      placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell
      only oral cholera vaccines in children and adult women in Bangladesh. We
      calculated whether there was an inverse, monotonic trend for the relation between
      the level of vaccine coverage in a residential cluster and the incidence of
      cholera in individual vaccine recipients or placebo recipients residing in the
      cluster after controlling for potential confounding variables. FINDINGS: Vaccine
      coverage of the targeted population ranged from 4% to 65%. Incidence rates of
      cholera among placebo recipients were inversely related to levels of vaccine
      coverage (7.01 cases per 1000 in the lowest quintile of coverage vs 1.47 cases
      per 1000 in the highest quintile; p<0.0001 for trend). Receipt of vaccine by an
      individual and the level of vaccine coverage of the individual's cluster were
      independently related to a reduced risk of cholera. Moreover, after adjustment
      for the level of vaccine coverage of the cluster, vaccine protective efficacy
      remained significant (55% [95% CI 41-66], p<0.0001). INTERPRETATION: In addition
      to providing direct protection to vaccine recipients, killed oral cholera
      vaccines confer significant herd protection to neighbouring non-vaccinated
      individuals. Use of these vaccines could have a major effect on the burden of
      cholera in endemic settings.

PMID- 15993233
TI  - Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60
      in juvenile idiopathic arthritis.
AB  - BACKGROUND: Juvenile idiopathic arthritis is a heterogeneous autoimmune disease
      characterised by chronic inflammation of one or more joints. In patients with
      this disease, T-cell reactivity to autologous heat-shock protein 60 (HSP60) is
      associated with a favourable prognosis. We sought to identify HSP60 T-cell
      epitopes to find potential targets for HSP60 immunotherapy and to assess whether
      immune responses to these epitopes contribute to the distinct clinical outcome of
      this disease. METHODS: We identified eight potential epitopes using a computer
      algorithm from both self and microbial HSP60 binding to many HLA-DR molecules. We
      analysed the pattern of T-cell responses induced by these HSP60 peptides in
      peripheral-blood mononuclear cells (PBMC) of 57 patients with juvenile idiopathic
      arthritis, 27 healthy controls, and 20 disease controls. We undertook in-vitro
      MHC binding studies with the identified peptides, and HLA class II typing of a
      subset of patients with juvenile idiopathic arthritis. FINDINGS: Five of the
      eight peptides identified yielded proliferative T-cell responses in 50-70% of
      PBMC from patients with juvenile idiopathic arthritis irrespective of MHC
      genotype, but not in PBMC from healthy or disease controls. Although PBMC from
      both patients with juvenile idiopathic arthritis and healthy controls produced
      interferon gamma in response to these peptides, only PBMC from patients with the
      disease produced interleukin 10. INTERPRETATION: The recorded T-cell-induction in
      juvenile idiopathic arthritis is tolerogenic. In patients with oligoarticular
      disease, the immune responses to the HSP60 epitopes identified could contribute
      to disease remission. RELEVANCE TO PRACTICE: The broad recognition of these HSP60
      epitopes in a population of patients with polymorphic MHC genotypes opens the way
      for HSP60-peptide immunotherapy, representing a novel treatment option to
      specifically modulate the immune system in patients with juvenile idiopathic
      arthritis.

PMID- 15993234
TI  - Sex work, drug use, HIV infection, and spread of sexually transmitted infections
      in Moscow, Russian Federation.
AB  - Rates of HIV-1 infection are growing rapidly, and the epidemic of sexually
      transmitted infections is continuing at an alarming rate, in the Russian
      Federation. We did a cross-sectional study of sexually transmitted infections,
      HIV infection, and drug use in street youth at a juvenile detention facility,
      adults at homeless detention centres, and women and men at a remand centre in
      Moscow. 160 (79%) women at the remand centre were sex workers. 91 (51%) homeless
      women had syphilis. At least one bacterial sexually transmitted infection was
      present in 97 (58%) female juvenile detainees, 120 (64%) women at the remand
      centre, and 133 (75%) homeless women. HIV seroprevalence was high in women at the
      remand centre (n=7 [4%]), adolescent male detainees (5 [3%]), and homeless women
      (4 [2%]). In view of the interaction between sexually transmitted infections and
      HIV infection, these findings of high prevalence of sexually transmitted
      infections show that these disenfranchised populations have the potential to make
      a disproportionately high contribution to the explosive growth of the HIV
      epidemic unless interventions targeting these groups are implemented in the
      Russian Federation.

PMID- 15993235
TI  - Pemphigus.
AB  - Pemphigus is a rare autoimmune disease that results in blistering of the skin and
      oral cavity. It is caused by autoantibodies directed against cell-surface
      antigens on keratinocytes, which when targeted lose their cellular adhesion
      properties and separate from one another to form blisters within the epidermis.
      Differences in the particular antigens targeted by the antibodies and in the
      distribution of these antigens in the different regions of the body and in the
      separate layers of the epidermis result in different clinical manifestations of
      the disease. The disease is diagnosed based on its clinical manifestations
      (flaccid blisters and erosions on skin and oral mucosa), histology (epidermal
      acantholysis), and immunological abnormalities (circulating and tissue-fixed
      antibodies against keratinocyte surface antigens). Pemphigus, which if left
      untreated is almost always fatal, is generally managed with topical, oral, or
      intralesional corticosteroids. Other options include plasmapheresis and
      intravenous immunoglobulin (IVIg), coupled with cytotoxic drugs.
      Immunosupressants, anti-inflammatory drugs, and antibiotics are used as
      adjuvants, but apart from IVIg, these therapy options are non-specific and more
      research is needed to develop treatments with improved side-effect profiles.

PMID- 15993236
TI  - Role of leptin in energy-deprivation states: normal human physiology and clinical
      implications for hypothalamic amenorrhoea and anorexia nervosa.
AB  - Leptin is an adipocyte-secreted hormone that plays a key part in energy
      homoeostasis. Advances in leptin physiology have established that the main role
      of this hormone is to signal energy availability in energy-deficient states.
      Studies in animals and human beings have shown that low concentrations of leptin
      are fully or partly responsible for starvation-induced changes in neuroendocrine
      axes, including low reproductive, thyroid, and insulin-like growth factor (IGF)
      hormones. Disease states such as exercise-induced hypothalamic amenorrhoea and
      anorexia nervosa are also associated with low concentrations of leptin and a
      similar spectrum of neuroendocrine abnormalities. We have recently shown in an
      interventional, proof-of-concept study that leptin can restore ovulatory
      menstrual cycles and improve reproductive, thyroid, and IGF hormones and bone
      markers in hypothalamic amenorrhoea. Further studies are warranted to establish
      the safety and effectiveness of leptin for the infertility and osteoporosis
      associated with hypothalamic amenorrhoea, and to clarify its role in anorexia
      nervosa.

PMID- 15993237
TI  - The whole truth and nothing but the truth? The research that Philip Morris did
      not want you to see.
AB  - The tobacco industry maintained, for many years, that it was unaware of research
      about the toxic effects of smoking. By the 1970s, however, the industry decided
      that it needed this information but they were unwilling to seek it in a way that
      was open to public scrutiny. By means of material from internal industry
      documents it can be revealed that one company, Philip Morris, acquired a research
      facility, INBIFO, in Germany and created a complex mechanism seeking to ensure
      that the work done in the facility could not be linked to Philip Morris. In
      particular it involved the appointment of a Swedish professor as a 'co
      ordinator', who would synthesise reports for onward transmission to the USA.
      Various arrangements were made to conceal this process, not only from the wider
      public, but also from many within Philip Morris, although it was known to some
      senior executives. INBIFO appears to have published only a small amount of its
      research and what was published appears to differ considerably from what was not.
      In particular, the unpublished reports provided evidence of the greater toxicity
      of sidestream than mainstream smoke, a finding of particular relevance given the
      industry's continuing denial of the harmful effects of passive smoking. By
      contrast, much of its published work comprises papers that convey a message that
      could be considered useful to the industry, in particular casting doubt on
      methods used to assess the effects of passive smoking.

PMID- 15993238
TI  - Infants refusing to walk.

PMID- 15993239
TI  - Bilateral groin pain from a rotten molar.

PMID- 15993240
TI  - Propagation of Ca2+ release in cardiac myocytes: role of mitochondria.
AB  - Factors contributing to "local control" of Ca2+ release in cardiac myocytes are
      incompletely understood. We induced local release of Ca2+ by regional exposure of
      mouse atrial and ventricular myocytes to 10mM caffeine for 500 ms using a rapid
      solution switcher. Propagation of Ca2+ release was imaged by means of a Nipkow
      confocal microscope, and fluo-3. Under physiologic conditions, a local release of
      Ca2+ propagated in atrial myocytes, not in ventricular myocytes. Inhibition of SR
      Ca2+ uptake (500 nM thapsigargin), and of Ca2+ extrusion via Na/Ca exchange (5mM
      Ni2+), did not result in propagation in ventricular myocytes. The density of
      mitochondria was greater in ventricular than in atrial myocytes, although the
      abundance of ryanodine receptors and myofilaments was similar. Partial inhibition
      of Ca2+ uptake via the mitochondrial Ca2+ uniporter (5 microM Ru360) caused an
      increase in the [Ca2+]i transient in paced ventricular myocytes, and consistently
      resulted in propagation of Ca2+ release. This effect of Ru360 did not appear to
      be due to altered SR Ca2+ content. These data indicate that Ca2+ uptake via the
      mitochondrial uniporter occurs on a beat-to-beat basis, and may contribute to
      local control of Ca2+ release. Propagation of Ca2+ release in atrial myocytes may
      result in part from the relatively low density of mitochondria present.

PMID- 15993241
TI  - Prevalence of cataract in rural Indonesia.
AB  - PURPOSE: To describe the prevalence of cataract in adults in rural Sumatra,
      Indonesia. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A random
      sample of all adults aged 21 years or older living in 3 rural villages in central
      Sumatra was assessed. Nine hundred nineteen of 1089 (84.4%) eligible adults
      participated. METHODS: A team of 7 ophthalmologists examined the anterior segment
      of both eyes using a portable slit lamp after pupil dilatation. Lens opacity was
      graded according to the Lens Opacities Classification System III (LOCS III). A
      structured questionnaire was used to collect data on education level and income.
      MAIN OUTCOME MEASURES: Cataract was defined as either a LOCS III nuclear region
      score of > or =4.0, cortical > or =4.0, or posterior subcapsular (PSC) cataract >
      or =2.0, in either eye. RESULTS: Two hundred one (21.9%) of 919 subjects were
      found to have cataract. The age-adjusted prevalence rate of cataract (including
      cataract surgery) was 23.0% (95% confidence interval, 20.8-25.2). The most common
      type of cataract for both genders (adjusted for age) was mixed (13%) followed by
      nuclear only (5.7%), and cortical only (4%). The prevalence rate of any cataract
      for adults aged 21 to 29 was 1.1%, increasing to 82.8% for those aged older than
      60 years. Similar trends with age were noted for nuclear, cortical, and PSC
      cataract. Women had higher prevalence rates than men for all types of cataract
      except cortical. There was a trend of increasing prevalence of all types of
      cataract with decreasing education (P<0.001). CONCLUSIONS: Cataract prevalence in
      adults aged 21 years and older in rural Indonesia is among the highest reported
      in Southeast Asia. Despite this, there are inadequate resources available to
      manage this treatable disease. Allocation of resources to tackle the present
      burden of cataract would likely have large personal, social, and economic
      benefits.

PMID- 15993242
TI  - Limbal allograft, amniotic membrane transplantation, and intraoperative mitomycin
      C for recurrent pterygium.
AB  - OBJECTIVE: To conduct a pilot study evaluating the efficacy and safety of limbal
      allograft, preserved amniotic membrane transplantation, and intraoperative
      mitomycin C treatment for recurrent pterygium. DESIGN: Prospective,
      noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 11
      patients with recurrent pterygium. The mean number of previous surgeries for
      pterygium was 1.9+/-1.4 (range, 1-6). INTERVENTION: All subjects received limbal
      allograft, preserved amniotic membrane transplantation, and intraoperative
      mitomycin C. MAIN OUTCOME MEASURES: Pterygium recurrence and complications.
      RESULTS: The mean follow-up period was 21.6+/-5.6 months (range, 16-36 months).
      There was no pterygium recurrence in any of the eyes. Symblepharon reappeared in
      3 eyes and diplopia recurred in 2 eyes. There were no other surgical
      complications and there was no graft rejection. CONCLUSIONS: Limbal allograft,
      preserved amniotic membrane transplantation, and intraoperative mitomycin C may
      be a safe and effective procedure for recurrent pterygium.

PMID- 15993243
TI  - Recurrent intraepithelial neoplasia treatment.

PMID- 15993244
TI  - Changes in the RNFL.

PMID- 15993248
TI  - Sheathotomy for vein occlusion.

PMID- 15993249
TI  - Vigabatrin toxicity in children.

PMID- 15993250
TI  - New mandate in resident education.

PMID- 15993252
TI  - COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at
      central and peripheral sites.
AB  - Despite the diverse chemical structure of aspirin-like drugs, the antinociceptive
      effect of NSAIDs is mainly due to their common property of inhibiting
      cyclooxygenases involved in the formation of prostaglandins. Prostaglandins are
      potent hyperalgesic mediators which modulate multiple sites along the nociceptive
      pathway and enhance both transduction (peripheral sensitizing effect) and
      transmission (central sensitizing effect) of nociceptive information. Inhibition
      of the formation of prostaglandins at peripheral and central sites by NSAIDs thus
      leads to the normalisation of the increased pain threshold associated with
      inflammation. The contribution of peripheral and central mechanisms to the
      overall antinociceptive action of NSAIDs depends on several factors including the
      location of the targets of drug action, the site of drug delivery and the uptake
      and distribution to the site of action. The present work reviews the data on the
      regulation and location of cyclooxygenases at central and peripheral sites of the
      nociceptive pathway and focuses on the role of COX in the generation and
      maintenance of pain hypersensitivity. Experimental and clinical evidences are
      used to evaluate the significance of the peripheral and central antihyperalgesic
      effects of NSAIDs.

PMID- 15993253
TI  - Nine-month predictors and outcomes of SSRI antidepressant continuation in primary
      care.
AB  - BACKGROUND: This study aimed to identify the predictors and outcomes of SSRI
      antidepressant continuation, discontinuation and switching over a 9-month period
      of naturalistic observation. METHODS: Primary care patients (n=573) with
      physician-diagnosed depression from 37 practices were randomized to an open-label
      trial of one of three selective serotonin reuptake inhibitors (SSRIs) managed in
      their primary care setting. Psychiatric characteristics and treatment course were
      assessed at baseline and at 1, 3, 6 and 9 months after medication initiation.
      RESULTS: Nineteen percent of patients switched SSRIs, which occurred
      significantly sooner than discontinuation (median: 41 vs.100 days). Time to
      discontinuation was primarily explained by baseline patient skepticism about
      taking an antidepressant (62% increase in discontinuation risk). In contrast,
      time to switch was associated with greater impairment at baseline and lesser
      improvement in impairment during the first month on medication. Patients who
      discontinued were significantly less likely to be depressed 9 months after
      starting medication than those who either continued or switched medication, and
      were less symptomatic and impaired than patients who switched. CONCLUSIONS:
      Baseline impairment may increase the risk for SSRI antidepressant switching.
      Additionally, patient skepticism about antidepressants predicts early SSRI
      discontinuation and may predict rapid recovery. Intent-to-treat analyses in
      nonrandomized clinical trials may paradoxically inflate antidepressant effect
      sizes.

PMID- 15993254
TI  - Medical illness and response to treatment in primary care panic disorder.
AB  - OBJECTIVE: Although studies have suggested that comorbid medical illness can
      affect the outcome of patients with depression, little is known about whether
      medical illness comorbidity affects treatment outcome in patients with anxiety.
      METHOD: Primary care patients with panic disorder (n=232), participating in a
      randomized collaborative care intervention of CBT and pharmacology, were divided
      into those above (n=125) and below (n=107) the median for burden of chronic
      medical illness and assessed at 3, 6, 9 and 12 months. RESULTS: Subjects with a
      greater burden of medical illness were more psychiatrically ill at baseline, with
      greater anxiety symptom severity, greater disability and more psychiatric
      comorbidity. The intervention produced significant and similar increases in
      amount of evidence-based care, and reductions in clinical symptoms and disability
      that were comparable in the more and less medically ill groups. CONCLUSIONS: The
      comparable response of individuals with more severe medical illness suggests that
      CBT and pharmacotherapy for panic disorder work equally well regardless of
      medical illness comorbidity. However, the more severe psychiatric illness both at
      baseline and follow-up in these same individuals suggest that treatment programs
      may need to be extended in time to optimize treatment outcome.

PMID- 15993255
TI  - Somatization and alexithymia in young adult Finnish population.
AB  - BACKGROUND: We assessed alexithymia and alexithymic features among young adult
      subjects with and without somatization symptoms in an epidemiological setting
      with a sample of young adults. METHODS: The sample consisted of urban 31-year-old
      subjects (N=1002). Data on somatization were gathered from a review of all public
      health outpatient records. Subjects with four or more somatization symptoms
      according to the DSM-III-R criteria were considered somatizers. The 20-item
      version of the Toronto Alexithymia Scale (TAS-20) was used to measure
      alexithymia. Subjects with a total TAS score over 60 were considered as being
      alexithymic, and those with a score under 52 were considered nonalexithymic.
      Subjects with a total TAS score from 52 to 60 were considered as having
      alexithymic features. RESULTS: The prevalence of alexithymia was 6.0% among
      somatizers and 4.8% among subjects without somatization symptoms, and the
      prevalence of alexithymic features was 7.5% and 12.6%, respectively. CONCLUSIONS:
      No association was found between alexithymia and somatization in young adult
      general population. The earlier theory of the association between alexithymia and
      somatization may be questionable.

PMID- 15993256
TI  - Religiosity, depression and pain in patients with breast cancer.
AB  - There is a growing body of evidence that religiosity can buffer depression and
      support the healing process. Our objective was to assess the relationship between
      religiosity, depression and pain in patients with breast cancer. Participants in
      our study were 115 breast cancer female patients recruited from a radiotherapy
      unit of a cancer teaching hospital, surveyed during the course of 6 months. The
      assessment used the Santa Clara Strength of Religious Faith Questionnaire as the
      measure of religiosity, and the subjects were categorized into low-, moderate-
      and high-religiosity groups according to its score. Depression was measured with
      the Center for Epidemiologic Studies Depression Scale, a 20-item self-report
      scale. The score of >or=16 indicated clinically relevant depression. A visual
      analogue scale was used for the assessment of pain. High religiosity was
      associated with a significantly lower prevalence of depression (chi(2)=6.635;
      df=2; P=.036), but religiosity was not related to the intensity of pain
      perception. Higher religiosity was associated with older age, lower education,
      unemployment and more children. Depression was associated with a higher pain
      level (U=1027.5; P=.004). The type of operation and tumor stage were not
      associated with categories of depression or religiosity, but mastectomized
      patients who belonged to the high-religiosity group were significantly less
      depressed (chi(2)=9.552; df=2; P=.008).

PMID- 15993257
TI  - The desire for death arises from an intolerable future rather than an intolerable
      present.

PMID- 15993258
TI  - Desire for death near the end of life: the role of depression, anxiety and pain.
AB  - OBJECTIVE: This study evaluated the desire of patients with advanced cancer for
      hastened death to determine its relationship to psychological distress, anxiety
      and pain. METHODS: One hundred twenty terminally ill cancer patients were
      surveyed from June to November 2003 at a palliative care unit in Athens, Greece.
      Greek versions of the Schedule of Attitudes Toward Hastened Death (G-SAHD), the
      Hospital Anxiety and Depression Scale (G-HADS) and the Brief Pain Inventory were
      administered. RESULTS: Significant correlations were seen between desire for
      hasten death and HADS-Depression (r=.605; P<.0005) and HADS-Anxiety (r=.636;
      P<.0005) scores. Results of multiple regression analyses showed that the HADS
      Depression scale (B=.443; P<.0005) as well as the HADS-Anxiety scale (B=.326;
      P<.0005) and the interaction between HADS-Depression and opioids (B=-.159;
      P=.012), but not pain intensity, pain-related interference, age, sex, patient's
      performance status as defined by the Eastern Cooperative Oncology Group as well
      as the interactions between average pain and opioids and average pain and HADS
      Depression, were significant predictors of G-SAHD scores. CONCLUSIONS: In
      terminally ill cancer patients, depression and anxiety as well as the interaction
      between HADS-Depression and opioids appeared to have a significant impact on the
      desire for hastened death while pain does not. Effective management of
      psychological symptoms seems to be an important aspect of adequate palliative
      care in order to reduce the desire for hastened death.

PMID- 15993259
TI  - Psychiatric disorders among patients admitted to a French medical emergency
      service.
AB  - OBJECTIVE: The authors assessed the prevalence of psychiatric disorders among a
      population of patients examined in the emergency service of a French general
      hospital. They compared patients with and without psychiatric disorders. They
      also compared patients where the primary motive of emergency was psychiatric to
      those whose psychiatric disorders were secondarily diagnosed by a systematic
      assessment. METHOD: Five hundred consecutive patients admitted to the emergency
      service of Bichat Claude Bernard Hospital (Paris, France) were interviewed with
      standardized questionnaires. Demographic details were collected along with
      information on current and past contacts with emergencies and psychiatric
      services. Psychiatric disorders were identified using a structured psychiatric
      interview, the Mini International Neuropsychiatric Interview (MINI). Domestic
      violence was identified with a specific checklist validated for this purpose.
      RESULTS: Prevalence of psychiatric disorders was 38% (189 patients). Forty (8%)
      patients were primary psychiatric cases referred to the emergency department for
      psychiatric reasons, while 149 (30%) were secondary psychiatric cases, as
      revealed by a systematic assessment of their mental state. Psychiatric patients,
      primary or secondary, were more often homeless (13.6% vs.1.95%). They had been
      more often referred to the emergency department after an aggressive (7.4%
      vs.3.5%) or violent behavior (5.8% vs.0.9%) and less often after an accident
      (8.4% vs.14.3%). Psychiatric patients were more often examined after an episode
      of domestic violence (21.7% vs. 6.8%). Psychiatric diagnoses, according to the
      DSM-IV criteria, were depression (80 cases), generalized anxiety disorder (34
      cases) acute alcohol intoxication (21 cases), alcohol dependence (20 cases),
      schizophrenia (16 cases), posttraumatic stress disorder (14 cases), drug abuse (4
      cases), agoraphobia (4 cases), alcohol abuse (3 cases), anorexia nervosa (3
      cases), mania (2 cases) and obsessive compulsive disorder (2 cases). The
      proportion of psychiatric diagnoses was equivalent in primary and secondary
      psychiatric cases except for schizophrenia (more often a primary demand for
      psychiatric help) and acute alcohol intoxication (more often revealed by a
      systematic assessment of the mental state). CONCLUSION: Thirty-eight percent of
      the patients examined in a French emergency service presented with psychiatric
      disorders. The majority of the patients (78%) were not referred to the emergency
      service for psychiatric reasons. Patients seen in an emergency service should
      thus be identified as a population at risk for psychiatric disorders whatever
      their reason for utilizing this service.

PMID- 15993260
TI  - Predicting community tenure in patients with recurrent utilization of a
      psychiatric emergency service.
AB  - OBJECTIVE: Factors determining community tenure (CT) between subsequent referrals
      to a psychiatric emergency room (PER) are only partly understood. We investigated
      the differential effect of patient and health system characteristics on the CT of
      patients with a previous referral to a PER. METHOD: Data were collected for
      patients with a history of PER referrals (N=531) in a university hospital in
      Leuven, Belgium, between March 2000 and March 2002. Using logistic regression
      analysis, we compared patients with a short (<2 months), intermediate (2--12
      months) and long (>or=12 months) CT between previous and current referrals.
      RESULTS: A short CT (53% of the patients) was predicted by not receiving
      aftercare at the previous PER visit (OR=6.43) or by not complying with
      recommended aftercare (OR=3.89). An intermediate CT (38% of the patients) was
      predicted by an adjustment disorder (OR=6.72) or a substance use disorder
      (OR=3.47) or by the absence of a mental disorder (OR=4.13). Nine percent had a
      long CT. Protective factors of a long CT were noncompliance with aftercare at the
      last PER visit (OR=0.09) and currently being in outpatient treatment (OR=0.05).
      CONCLUSION: For patients with a previous use of a PER, short CT was highly
      influenced by aftercare arrangements and not by clinical characteristics.

PMID- 15993261
TI  - Using the Hospital Anxiety and Depression Scale to screen for depression in
      cardiac patients.
AB  - OBJECTIVE: There is an increasing interest in trying to identify patients with
      chronic physical illness who would benefit from interventions to decrease
      psychological distress. The Hospital Anxiety and Depression Scale (HADS) is one
      measure that can be effectively used to identify patients struggling with anxiety
      and/or depression in addition to comorbid medical illness such as cardiac
      disease. The aim of this study is to determine if the HADS correctly identified
      patients with depression according to the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition [determined using the Primary Care Evaluation of
      Mental Disorders (PRIME-MD), a gold-standard diagnostic tool], as depressed and
      to determine which items on the HADS most strongly predicted the PRIME-MD major
      depression diagnosis among cardiac patients. METHOD: Patient data were obtained
      from a randomized controlled trial of treatment for psychological distress in
      patients surviving recent myocardial infarction or life-threatening ischemic
      heart disease. The HADS was used to evaluate depression and/or anxiety among
      patients hospitalized for heart disease, and the PRIME-MD was used to diagnose
      major depressive disorder (MDD) in these patients. We used receiver-operating
      characteristic (ROC) curves and logistic regression to analyze patient responses
      to both of these measures. RESULTS: Among the 79 study patients, the area under
      the ROC curve (AUC) for the HADS depression subscale was 0.81 with an S.E. of
      0.05, and the AUC was 0.70 for the HADS anxiety subscale with an S.E. of 0.06.
      Using a cutoff of 7 on each HADS subscale to determine PRIME-MD diagnosis of MDD,
      the sensitivity and specificity were 81% and 54%, respectively, for the
      depression subscale and 81% and 40%, respectively, for the anxiety subscale. In
      addition, a few individual HADS items predicted PRIME-MD diagnosis of MDD,
      namely, concentration and positive anticipation (depression items) and relaxed
      and worry (anxiety items), each of which were strongly correlated with PRIME-MD
      diagnosis of MDD. Finally, items positive anticipation and relaxed provided
      reasonable approximations to the results found from the HADS depression subscale
      measure, which performed better than the HADS anxiety subscale in predicting
      PRIME-MD diagnosis of depression. CONCLUSIONS: Using the HADS to detect mental
      disorders in primary care populations can save valuable physician time, and
      perhaps ensure that patients are treated for their mental distress as well as
      medical disease.

PMID- 15993262
TI  - The relationship between interpersonal problems and occupational stress in
      physicians.
AB  - OBJECTIVE: This article examined the associations between occupational stress and
      interpersonal problems in physicians. METHOD: A nationwide representative sample
      of Norwegian physicians received the 64-item version of the Inventory of
      Interpersonal Problems (IIP-64) (N=862, response rate=70%) and six instruments
      measuring occupational stress. Comparison of means, correlation and reliability
      statistics and multiple regression analyses were applied. RESULTS: The IIP-64
      total score had a significant impact on job satisfaction, perceived unrealistic
      expectancies, communication with colleagues and nurses and on stress from
      interaction with patients. Being overly subassertive was related to low job
      satisfaction. Being overly expressive was linked to the experience of unrealistic
      expectancies from others and lack of positive feedback, whereas overly
      competitive physicians tended to have poorer relationships with both colleagues
      and nurses. CONCLUSIONS: Addressing interpersonal problems in medical school and
      postgraduate training may be a valuable measure to prevent job stress and promote
      quality of care.

PMID- 15993263
TI  - Treatment of psychomotor agitation and self-injurious behavior with estrogen and
      progesterone in a patient with Sanfilippo syndrome.

PMID- 15993264
TI  - Pavor nocturnus as a side effect of a single daily risperidone dose.

PMID- 15993265
TI  - Cryptococcal meningitis mimicking primary mania in a young female.

PMID- 15993266
TI  - Polysomy 8 defines a clinico-cytogenetic entity representing a subset of myeloid
      hematologic malignancies associated with a poor prognosis: report on a cohort of
      12 patients and review of 105 published cases.
AB  - Tetrasomy, pentasomy, and hexasomy 8 (polysomy 8) are relatively rare compared to
      trisomy 8. Here we report on a series of 12 patients with acute myeloid leukemia
      (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD)
      associated with polysomy 8 as detected by conventional cytogenetics and
      fluorescence in situ hybridization (FISH). In an attempt to better characterize
      the clinical and hematological profile of this cytogenetic entity, our data were
      combined with those of 105 published patients. Tetrasomy 8 was the most common
      presentation of polysomy 8. In 60.7% of patients, polysomy 8 occurred as part of
      complex changes (16.2% with 11q23 rearrangements). No cryptic MLL rearrangements
      were found in cases in which polysomy 8 was the only karyotypic change. Our study
      demonstrates the existence of a polysomy 8 syndrome, which represents a subtype
      of AML, MDS, and MPD characterized by a high incidence of secondary diseases,
      myelomonocytic or monocytic involvement in AML and poor overall survival (6
      months). Age significantly reduced median survival, but associated cytogenetic
      abnormalities did not modify it. Cytogenetic results further demonstrate an in
      vitro preferential growth of the cells with a high level of aneuploidy suggesting
      a selective advantage for polysomy 8 cells.

PMID- 15993267
TI  - Losses of 1p and chromosome 14 in renal oncocytomas.
AB  - We performed cytogenetic analyses of 8 renal oncocytomas to identify chromosomal
      regions involved in the tumorigenesis of oncocytomas. All cases showed
      chromosomal findings corresponding to established cytogenetic subsets of renal
      oncocytomas: 3 cases with normal karyotypes, 1 case with rearrangement of 11q,
      and 4 cases with losses of chromosome 14. In the latter cytogenetic subgroup,
      monosomy 14 was additionally accompanied by either monosomy 1 in 2 cases or loss
      of 1p in a third case, providing insights in the cytogenetic evolution of this
      subgroup.

PMID- 15993268
TI  - Characterization of ABCG2 gene amplification manifesting as extrachromosomal DNA
      in mitoxantrone-selected SF295 human glioblastoma cells.
AB  - The human ABCG2 gene, located on chromosome 4, encodes an ATP-binding cassette
      half-transporter that has been shown to confer resistance to chemotherapeutic
      agents. Relatively little is known about the mechanisms controlling expression of
      ABCG2. In previous studies, we had shown that overexpression of ABCG2 can result
      from rearrangement or gene amplification involving chromosome 4. To better
      characterize the mechanisms of ABCG2 overexpression, SF295 glioblastoma cells
      were exposed to increasing amounts of mitoxantrone to generate the SF295 MX50,
      MX100, MX250, and MX500 sublines, maintained in mitoxantrone concentrations
      ranging from 50 to 500 nmol/L. Northern blot analysis confirmed overexpression of
      ABCG2 mRNA, and immunoblot analysis demonstrated increased protein expression in
      the selected cell lines. Efflux of BODIPY-prazosin confirmed a functional
      protein. ABCG2 gene amplification was observed in all resistant sublines, as
      determined by Southern blot analysis. Fluorescence in situ hybridization (FISH)
      revealed amplification of ABCG2 via double minute chromosomes (dmins) detected in
      metaphase chromosome spreads in the SF295 MX50 and MX100 sublines. At higher
      levels of drug selection, in the MX250 and MX500 sublines, fewer dmins were
      observed but homogeneously staining regions (hsr) were visible with FISH
      analysis, revealing reintegration of the ABCG2 gene into multiple chromosomes.
      Spectral karyotyping (SKY) demonstrated multiple clonal and nonclonal
      rearrangements of chromosome 4, including hsrs. These results suggest that
      amplification of ABCG2 occurred initially in the form of dmins, followed by
      chromosomal reintegration of the amplicon at multiple sites. This occurred with
      increasing drug-selection pressure, generating a more stable genotype.

PMID- 15993269
TI  - Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene
      loci in breast cancer cell lines.
AB  - Loss of genetic material from chromosome arm 8p occurs frequently in human breast
      carcinomas, consistent with this region of the genome harboring one or more tumor
      suppressor genes (TSGs). We used the complementary techniques of microsatellite
      based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines
      (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular
      cytogenetic changes occurring on chromosome 8 during tumorigenesis, with
      particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations
      of chromosome 8, including partial or complete deletion of 8p or 8q, duplication
      of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex
      rearrangements of 8p with differing breakpoints of varying proximity to the genes
      of interest. High rates of LOH were observed at markers adjacent to or within
      PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due
      to the complex ploidy status of these cell lines, relative loss of 8p material
      detected by CGH did not always correlate with microsatellite-based LOH results.
      These results extend our understanding of the mechanisms accompanying the
      dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and
      identify appropriate cellular systems for further investigation of their
      biological properties.

PMID- 15993270
TI  - Genetic losses in breast cancer: toward an integrated molecular cytogenetic map.
AB  - Breast cancer is the most common malignant disease in Caucasian women, but is
      less frequent in Chinese women. The molecular basis for such ethnical difference
      in disease pathogenesis remains unknown. To address this issue, we performed
      allelotyping analysis of formalin-fixed, paraffin-embedded samples from 21
      Chinese patients with breast cancer using 59 fluorescently tagged oligonucleotide
      primers amplifying microsatellite loci. Loss of heterozygosity (LOH) was found in
      all tumor samples. Frequent allelic losses were identified at markers D3S1578
      (56%); D7S507 (55%); D1S2766 (50%); D17S789 and D17S946 (43% each); D19S814
      (35%); D2S162, D13S158 and D13S296 (33% each); D1S551 and D1S2800 (29% each);
      D3S1597 and D6S260 (22% each); and D1S1588 (21%). To compare our data to previous
      reports, we determined the band-specific frequency of chromosomal imbalances in
      breast cancer karyotypes reported in the Mitelman database, and from the CGH
      results of cases accessible through the Progenetix website. Furthermore,
      published LOH analyses of breast cancer cases were compared to our own LOH
      results, demonstrating the most common chromosomal regions affected by allelic
      losses. The combined results provide a comprehensive view of genetic losses in
      breast cancers, indicating the comparability of these different techniques and
      suggesting the presence of a distinct subset of breast cancers with high
      frequency LOH at chromosomes 1 and 2p in Chinese patients.

PMID- 15993271
TI  - Chromosome alterations in colorectal cancer in Thai patients.
AB  - Much information has been reported on the genetic and genomic alterations in
      colorectal cancer (CRC) in various countries; however, nonrandom chromosomal
      alterations in Thai patients have not been described. As a first step toward
      understanding the underlying genetic changes and determining early chromosomal
      changes of tumor development in this population, we used comparative genomic
      hybridization (CGH) to screen for losses and gains of DNA sequences along
      chromosomes in 20 morphologically normal tumor surroundings (MNTS) and 40 CRC
      tissues from 40 patients. In CRC, we detected gains of chromosome arms 20q (60%),
      8q (25%), 19q (22.5%), and 19p (20%), as well as losses of chromosome arms 18q
      (25%) and 4q (20%). There were no differences in genetic alteration between colon
      and rectal cancer. In morphologically normal tumor surroundings (MNTS) tissues,
      gains on 19p and 19q were most frequent. We suggest that gains of this chromosome
      are early events in the progression of CRC, followed by gains on 8q and 20q and
      losses on 4q and 18q at later stages. Based on our cytogenetic data by comparison
      of 2 tissue groups in the same cases, we discuss the monoclonal model followed by
      lateral epithelial spread as an explanation of multiple CRC. Identification and
      characterization of the causative genes for these cancer syndromes have enabled
      precise pre-symptomatic detection of mutations in individuals who bear a prior
      risk of developing CRC.

PMID- 15993272
TI  - An intronic variant in the TP53 gene in a Brazilian woman with breast cancer.
AB  - We screened the TP53 gene for mutational status in 40 breast tumor cases by
      polymerase chain reaction, single-strand conformational polymorphism, and gene
      sequencing. Many mutations of this gene have been described in specific
      databases. In our study, a new T-->C point mutation was identified in intron 6 at
      position 13989 in a grade III medullary ductal carcinoma. Other variations in
      intron 6 have been described in patients with Li-Fraumeni syndrome. One of these
      variations was reported to inhibit apoptosis and prolong cell survival, thereby
      increasing breast cancer risk. Nevertheless, more studies are necessary to
      establish whether this mutation has a role in breast cancer risk.

PMID- 15993273
TI  - Hereditary breast cancer syndromes in a Turkish population. Results of molecular
      germline analysis.
AB  - Breast cancer is the most common malignancy which affects women. In 5-10% of all
      cases, breast cancer presents as a hereditary cancer syndrome. Since 1996, 68
      families with suspicion of familial breast cancer have been referred to our
      department. In 5 of the 68 families (7.4%), the clinical diagnosis was hereditary
      breast ovarian cancer syndrome. In 17 families (25%), two or more breast cancer
      cases were present. Mutation screening of BRCA1 and BRCA2 in these families
      revealed a BRCA1 mutation (185delAG) in one family. Three families (4.4%) had a
      diagnosis of Li-Fraumeni syndrome and germline mutations in TP53 (Lys292Ile,
      Pro278Ser and Pro278Thr). Breast cancer occurred in a family with hereditary
      nonpolyposis colon carcinoma (HNPCC; Lynch syndrome) carrying an MLH1 mutation
      (IVS17-3G>C). Most of our families (41 families; 60.2%) had only one case with
      breast cancer or cystic adenoma (or both) and did not need counseling and DNA
      testing. In summary, in 10 of the 68 families in our series (14.7%), a germline
      mutation in a breast cancer predisposing gene was detected. Our data show the
      importance of detailed examination of clinical data, pedigree analyses, and
      molecular germline diagnostics for the counseling of breast cancer cases.

PMID- 15993274
TI  - No evidence of INI1hSNF5 (SMARCB1) and PARVG point mutations in oligodendroglial
      neoplasms.
AB  - Allelic losses of chromosome 22 found in oligodendrogliomas suggest that at least
      one tumor suppressor gene on chromosome 22 is inactivated during the multistep
      process of tumorigenesis in this glial tumor. INI1hSNF5 (HUGO symbol: SMARCB1),
      located at 22q11, encodes a component of the ATP-dependent chromatin remodeling
      hSWI-SNF complex; it is a tumor suppressor gene that is mutated in several
      malignant tumors. The PARVG gene, located at 22q13, has been found to exhibit
      reduced expression in some cancer lines. Both genes are thus candidate tumor
      suppressors, potentially involved in the pathogenesis of gliomas. We performed
      mutation analyses of INI1hSNF5 and PARVG in a series of 40 oligodendrogliomas,
      but only sequence polymorphic variations were identified. Accordingly, INI1hSNF5
      and PARVG do not seem to be the tumor suppressor genes involved in
      oligodendroglioma development and progression.

PMID- 15993276
TI  - Gain of 9p due to an unbalanced rearrangement der(9;18): a recurrent clonal
      abnormality in chronic myeloproliferative disorders.
AB  - Clonal aberrations leading to gain of 9p--mostly due to trisomy 9--are often
      reported in polycythemia vera. We report on four cases of chronic
      myeloproliferative disorders that demonstrated a new recurrent unbalanced
      rearrangement between chromosomes 9 and 18 leading to trisomy of 9p and a
      monosomy of 18p. This abnormality was confirmed with fluorescence in situ
      hybridization using chromosome painting and locus-specific probes. Three cases
      were diagnosed as polycythemia vera; one case presented with secondary acute
      myeloid leukemia following idiopathic osteomyelofibrosis. The prognostic impact
      of this unbalanced aberration and of gains of 9p in chronic myeloproliferative
      disorders remains to be clarified.

PMID- 15993275
TI  - Identification of a ring chromosome with spectral karyotyping in a pleural
      synovial sarcoma.
AB  - The origin of a ring chromosome in a monophasic synovial sarcoma of the
      diaphragmatic pleura of an 18-year-old man was investigated using spectral
      karyotyping (SKY) and fluorescence in situ hybridization (FISH). Conventional
      cytogenetic analysis revealed the following clonal karyotypic abnormalities:
      47,Y,t(X;18)(p11.2;q11.2),t(11;19)(q12;q13.4),+12,-13,+r[6]. The SYT-SSX1 fusion
      transcript was detected with reverse transcriptase-polymerase chain reaction
      analysis. SKY analysis suggested that the ring chromosome was composed of
      material from chromosome 8. Subsequent FISH analysis with a whole-chromosome 8
      paint probe confirmed the SKY results. This study demonstrates the usefulness of
      SKY as an adjunct for determining the chromosomal composition of ring
      chromosomes.

PMID- 15993277
TI  - Deletions of the 3'BCR and 5'ABL regions in patients with Philadelphia-positive
      chronic myeloid leukemia: a one-step process occurring in about 10% of the cases
      without any evidence of genetic instability in the target cells.
AB  - Deletions of the 5'ABL region adjacent to the t(9;22)(q34;q11) have recently been
      reported in 8-32.7% of patients with chronic myeloid leukemia (CML). The
      deletions were visualized with fluorescence in situ hybridization using, in the
      majority of the cases, the Vysis LSI BCR/ABL ES (extra signal) probe. In our
      series, 10 of 99 CML patients (10.1%) were characterized by a 5'ABL deletion. We
      show that 3'BCR losses are observed in nearly all the cases with 5'ABL deletions.
      Moreover, the different genetic events (Philadelphia chromosome formation; 5'ABL
      and 3'BCR deletions) occur simultaneously in a one-step process without any
      evidence for genetic instability in the target bone marrow cells.

PMID- 15993278
TI  - Prognostic significance of del(20q) in patients with hematological malignancies.
AB  - Deletions of the long arm of chromosome 20 represent a common chromosomal
      abnormality associated with myeloid malignancies, in particular with
      myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), and acute
      myeloid leukemia (AML). Using G-banding cytogenetic techniques, we found clones
      with del(20q) in 36 patients with hematological malignancies examined in our
      laboratory during the years 2001-2003: in 23 patients as a sole cytogenetic
      aberration and in 13 patients together with other chromosomal changes.
      Fluorescence in situ hybridization (FISH) with a probe specific for the 20q12
      region was used in all cases to confirm the presence of the clone with deletion.
      For patients with additional or complex chromosomal rearrangements, multicolor
      FISH (M-FISH) analysis was performed. Statistical evaluation of the prognostic
      impact of sex, age, diagnosis, and karyotype was performed. The survival time
      correlated with the type of chromosomal aberration; no significant differences in
      survival were found for sex, age, and diagnosis.

PMID- 15993279
TI  - Delay in diagnosis and its effect on outcome in head and neck cancer.
AB  - We examined the records of two cohorts of patients who were seen from 1960 to
      1999 with a diagnosis of squamous cell carcinoma (SCC) of the mouth and throat,
      one series being retrospective (n=400) and the other prospective (n=213) to find
      out about delays in diagnosis. The median delay in both cohorts was 3 months and
      the patients were responsible for the delay in most cases (n=319, 81% and n=160,
      78%, respectively). Half the patients in each cohort had delayed diagnoses
      (n=217, 54% and n=119, 56%, respectively) and similar percentages (n=110, 53% and
      n=172, 47%) presented with advanced disease (stage III or IV). These were not the
      same patients for there was no correlation between delay and stage or survival.
      Logistic regression analysis showed that non-white race (p=0.01) and high-grade
      histology (p=0.002) predicted advanced disease. The proportion of patients
      presenting with advanced disease had not changed in 40 years despite public
      education. We suggest that some tumours may be silent and that initial symptoms
      do not reliably predict early disease.

PMID- 15993280
TI  - Anatomical variability of omohyoid and its relevance in oropharyngeal cancer.
AB  - AIMS: To define the reproducibility of the position of omohyoid muscle. SETTING:
      A regional Maxillofacial surgical oncological service. MATERIAL AND PATIENTS:
      Thirty dissections of cadavers and consecutive series of 88 patients who had had
      neck dissections, either prophylactic or therapeutic, as part of their
      oncological management. METHOD: Measurement of the upper border of omohyoid
      muscle relative to the clavicle and the internal jugular vein (mm). RESULTS: The
      position of omohyoid muscle in relation to the clavicle and internal jugular vein
      varied considerably and by inference the nodal yield at level IV is also likely
      to vary. CONCLUSION: The wide variability of the position of omohyoid muscle is
      likely to have implications for the surgical management of oral and oropharyngeal
      cancer.

PMID- 15993281
TI  - Perception by the public and medical profession of oral and maxillofacial surgery
      -has it changed after 10 years?
AB  - Departments of oral and maxillofacial surgery (OMFS) aim to deliver an efficient
      and effective service. Clear understanding of what the speciality offers is
      central to appropriate referrals. Studies published 10 years ago showed there was
      limited awareness of the specialty. We present the results of a simple
      questionnaire study and compare the results with those of a previous survey.
      There has been some improvement in the perception of the role of OMFS, but only
      34/100 of the public had heard of OMFS and none expected OMFS to treat patients
      who were unhappy with their facial appearance.

PMID- 15993282
TI  - Image-guided navigation in oral and maxillofacial surgery.
AB  - Image-guided surgery is the logical extension of imaging as it integrates
      previously acquired radiological or nuclear medicine images with the operative
      field. In conventional image-guided surgery, a surgeon uses a surgical instrument
      or a pointer to establish correspondence between features in the preoperative
      images and the surgical scene. This is not ideal because the surgeon has to look
      away from the operative field to view the data. Augmented reality guidance
      systems offer a solution to this problem but are limited by deformation of soft
      tissues. Real-time intraoperative imaging offers a potential solution but is
      currently only experimental. The additional precision and confidence that this
      technology provides make it a useful tool, and recent advances in image-guided
      surgery offer new opportunities in the field of oral and maxillofacial surgery.
      Here, we review the development, current technologies, and applications of image
      guided surgery and illustrate them with two case reports.

PMID- 15993283
TI  - The outcome of various cements in combination with titanium reconstruction plates
      after segmental resection of the mandible.
AB  - We report on 82 patients who had segmental resection of the mandible and
      immediate reconstruction with titanium plates, which were supplemented by
      polymethylmethacrylate cement (n=32), glass ionomer cement (n=27), silicone
      (n=9), or nothing (n=14). The mean (S.D.) follow-up time was 92 (26) months. Six
      months after operation, 27 (46%) of the plates with polymethylmethacrylate cement
      or glass ionomer cement were removed. During the same time period, four (28%) of
      the plates were removed in the group with no additional material and two (22%) in
      the group that had silicone. There was a significant difference in survival time
      of the metal between the group with silicone and the group with glass ionomer
      cement (p=0.014, log rank). Although silicone performed slightly better than the
      reconstruction plate on its own, we doubt whether any cement is necessary.

PMID- 15993284
TI  - Outcome of 50 consecutive sinus lift operations.
AB  - We report 50 patients who had sinus lift operations between 1995 and 1999 using
      different grafting materials [autologous bone, heterologous bone, and
      hydroxyapatite]. The casenote were analysed clinically (intraoperative and
      postoperative results and complications), radiographically (amount of augmented
      bone 6 months postoperatively), and histologically (quality of the new bone 12
      months postoperatively). Our aim was to find out if the various bone grafting
      materials used resulted in different outcomes after adjustment for significant
      predictors. We found that hydroxyapatite was associated with the lowest rate of
      loss of grafted material (median, 2.4 mm) followed by the autologous bone from
      iliac crest (2.8 mm). Bovine bone shown the highest loss (3.3 mm).

PMID- 15993285
TI  - Buccal mucosal grafts for urethroplasty: surgical technique and morbidity.
AB  - We present an outline of the surgical technique for harvesting free buccal
      mucosal grafts for urethroplasty in 23 patients and an assessment of morbidity at
      the donor site. Any problems were recorded, particularly injury to the lingual
      and mental nerves, symptoms of obstruction of the parotid duct, and trismus.
      There were four early (less than 6 weeks) complaints of mild trismus and one late
      complaint. All the grafts were successful.

PMID- 15993286
TI  - Penetrating arrow injuries of the maxillofacial region.
AB  - We operated on four civilian patients who had unusual penetrating maxillofacial
      injuries that resulted from assault with arrows. The patients were fully
      conscious at the time of presentation. Recovery was uneventful in three, but one
      died.

PMID- 15993287
TI  - Recurrence of a solitary bone cyst of the mandible: case report.
AB  - We report a case of a solitary bone cyst in the mandible of an elderly woman who
      presented with a bilateral radiolucent lesion that caused bony expansion, and
      which recurred 30 months after enucleation and bone grafting of the cavity.

PMID- 15993288
TI  - Darier disease: a case report.
AB  - The diagnosis of Darier disease of the oral mucosa was made only after biopsying
      a leukoplakia-like lesion of the palate.

PMID- 15993289
TI  - Aesthetic modification of the maxillary dressing plate for use during preimplant
      augmentation of the anterior ridge.

PMID- 15993290
TI  - Spatula bruises and monitoring of free flaps.

PMID- 15993291
TI  - Re: Polymorphous low-grade adenocarcinoma-a rare and aggressive entity in
      adolescence.

PMID- 15993292
TI  - Interesting case: Arch bar support using self-drilling intermaxillary fixation
      screws.

PMID- 15993293
TI  - Interesting case: Factitious illness (Munchausen's syndrome)--report of a case.

PMID- 15993294
TI  - Catalytic reduction of chlorinated and recalcitrant compounds in contaminated
      water.
AB  - Catalysis dechlorination of chlorinated organic matter by palladium/iron
      bimetallic particles represents one of the latest innovative technologies for
      contaminated soil and groundwater remediation. The reaction of dechlorination is
      believed to take place on the surface site of the catalyst in a pseudo-first
      order mode. The dechlorination rate increases with an increase of the bulk
      loading of palladium due to the increase of both the surface loading of palladium
      and the total surface area exposed. The results show that no other intermediates
      were generated besides Cl-, benzene and chlorobenzene during dechlorination of o
      dichlorobenzene.

PMID- 15993295
TI  - Extraction kinetics of heavy metal-containing sludge.
AB  - In order to remove and recover copper, zinc, cadmium, and chromium from the
      wastewater treatment sludge generated by an electroplating process, the heavy
      metal extraction kinetics was studied in a batch reactor using two different
      extraction agents (nitric and citric acid) at constant agitation speed (150 rpm)
      and solid to liquid ratio (10 g/L), but varying acid concentrations (0.02-0.10
      N), temperatures (25-85 degrees C in nitric acid solution, 25-95 degrees C in
      citric acid solution), and sludge particle sizes. The shrinking-core model and
      empirical kinetic model were adopted to analyze the experimental data. Although
      both models could fit the experimental kinetic data well, the obtained parameters
      of the shrinking-core model did not show reasonable trends varying with the
      experimental variables while the empirical model parameters showed significant
      trends. The experimental and modeling results showed that the metal extraction
      rates increased with acid concentration, temperature, but decreased with
      increasing particle size. Nitric acid was found to be more effective than citric
      acid to extract the heavy metals from the sludge. The extraction activation
      energies obtained in this study suggested that both a physical diffusion process
      and a chemical reaction process might play important roles in the overall
      extraction process.

PMID- 15993296
TI  - Mechanisms and kinetics models for ultrasonic waste activated sludge
      disintegration.
AB  - Ultrasonic energy can be applied as pre-treatment to disintegrate sludge flocs
      and disrupt bacterial cells' walls, and the hydrolysis can be improved, so that
      the rate of sludge digestion and methane production is improved. In this paper,
      by adding NaHCO3 to mask the oxidizing effect of OH, the mechanisms of
      disintegration are investigated. In addition, kinetics models for ultrasonic
      sludge disintegration are established by applying multi-variable linear
      regression method. It has been found that hydro-mechanical shear forces
      predominantly responsible for the disintegration, and the contribution of
      oxidizing effect of OH increases with the amount of the ultrasonic density and
      ultrasonic intensity. It has also been inferred from the kinetics model which
      dependent variable is SCOD+ that both sludge pH and sludge concentration
      significantly affect the disintegration.

PMID- 15993297
TI  - Equilibrium, kinetic and thermodynamic studies on the adsorption of phenol onto
      chitin.
AB  - The adsorption of phenol onto chitin, a naturally occurring material was studied
      as a function of initial pH, temperature and initial phenol concentration. The
      highest phenol adsorption capacity was determined as 21.5 mgg(-1) for 300 mgdm(
      3) initial phenol concentration at pH 1.0 and 40 degrees C. Adsorption data were
      well described by the Freundlich Model, although they could be modeled by the
      Langmuir equation. The pseudo-first-order and pseudo-second-order kinetic models
      were applied to test the experimental data. The pseudo-second-order kinetic model
      provided the best correlation of the experimental data compared to the pseudo
      first-order model. The thermodynamic constants of the adsorption process; DeltaG
      degrees , DeltaH degrees and DeltaS degrees were evaluated as -19.4 kJmol(-1) (at
      40 degrees C), 10.2 kJmol(-1) and 0.093 kJmol(-1)K(-1), respectively. These
      showed that adsorption of phenol on chitin was endothermic and spontaneous.

PMID- 15993298
TI  - Application of the central composite design and response surface methodology to
      the advanced treatment of olive oil processing wastewater using Fenton's
      peroxidation.
AB  - The central composite design (CCD) technique was used to study the effect of the
      Fenton's peroxidation on the removal of organic pollutants from olive oil mill
      wastewater (OMW). The ratio of hydrogen peroxide-to-Fe(II) (x1) was between 1.67
      and 8.33. Fe(II) concentration was constant at 0.03 M while the H2O2
      concentration was set at three levels: 0.05, 0.15 and 0.25 M. Based on the
      molarity ratio, the selected ratio were in the low range of Fe(II)-to-H2O2 ratio
      (<<1). While based on the wt/wt ratio, the tested Fe(II)-to-H2O2 ratios were in
      the range of < or =1:5. pH (x2) was between 3 and 5. The concentration of OMW
      (x3) was varied between 40 and 100%. The influence of these three independent
      variables on the four dependent variables, i.e. COD, total phenolics (TP), color
      and aromaticity removal was evaluated using a second-order polynomial multiple
      regression model. Analysis of variance (ANOVA) showed a high coefficient of
      determination (R2) value of 0.902-0.998, thus ensuring a satisfactory adjustment
      of the second-order regression model with the experimental data. H2O2-to-Fe(II)
      ratio had significant effect on all the four dependent variables. The positive
      sign for the regression coefficient of this regressor variable indicated that the
      level of the pollutant removal increased with the increased levels of factor x1
      from 1.67 to 8.33 and this effect was the most pronounced for TP removal. pH had
      also significant effect on the pollutant removal and the effect was the most
      noticeable for TP reduction. The negative coefficient of this variable (pH)
      indicated that level of the pollutant removal decreased as the pH increased from
      3 to 5. The negative coefficient of the interaction between variable x1 and x2
      indicated that a simultaneous increase in H2O2-to-Fe(II) ratio with decrease in
      the pH of the reaction led to an increase in the COD, TP and color removal.
      Quadratic models were predicted for the response variable, i.e. pollutant
      removal, and the maximum model-predicted removals were 56, 100, 33 and 32% for
      COD, TP, color and aromaticity, respectively. Optimum conditions for this
      wastewater treatment was obtained based on the performance of the Fenton's
      peroxidation in the experiment where the H2O2-to-Fe(II) ratio was at its high
      level (8.33) and the pH and OMW concentration were 4 and 70%, respectively.

PMID- 15993299
TI  - Comparison of linear and non-linear method in estimating the sorption isotherm
      parameters for safranin onto activated carbon.
AB  - Comparison analysis of linear least square method and non-linear method for
      estimating the isotherm parameters was made using the experimental equilibrium
      data of safranin onto activated carbon at two different solution temperatures 305
      and 313 K. Equilibrium data were fitted to Freundlich, Langmuir and Redlich
      Peterson isotherm equations. All the three isotherm equations showed a better fit
      to the experimental equilibrium data. The results showed that non-linear method
      could be a better way to obtain the isotherm parameters. Redlich-Peterson
      isotherm is a special case of Langmuir isotherm when the Redlich-Peterson
      isotherm constant g was unity.

PMID- 15993300
TI  - Maintaining physical therapy standards in an emergency situation: solutions after
      the Bali bombing disaster.
AB  - In a mass casualty event, treatment is traditionally provided in a 'best for the
      most' fashion. This paper examines the challenges encountered by physical
      therapists while providing rehabilitation to 28 survivors who suffered burns
      after the terrorist bombing in Bali, Indonesia. Individual patient input was
      achieved with routine outcome measures and workload statistics. Workforce
      expansion, maintenance of treatment quality, and other practical initiatives used
      in order to achieve this goal are discussed.

PMID- 15993301
TI  - A silver coated dressing reduces the incidence of early burn wound cellulitis and
      associated costs of inpatient treatment: comparative patient care audits.
AB  - In 2000 and 2002, the Royal Perth Hospital (RPH) Burn Unit, Western Australia,
      conducted two 'before and after' patient care audits comparing the effectiveness
      and cost of Silvazine (silver sulphadiazine and chlorhexidine digluconate cream)
      and Acticoat, a new dressing product for in-patient treatment of early burn
      wounds. The main outcome variables were: burn wound cellulitis, antibiotic use
      and cost of treatment. Two patient care audits and a comparative sample were
      used. The two regimes audited were, 'standard treatment' of twice daily showers
      or washes with 4% chlorhexidine soap and Silvazine cream as a topical dressing
      (2000, n=51), compared with the 'new treatment' of daily showers of the burn
      wound with 4% chlorhexidine soap and the application of an Acticoat dressing
      (2002, n=19). In 2002, costs were also examined using a sample of matched pairs
      (n=8) of current and previous patients. The main findings were: when using
      Acticoat the incidence of infection and antibiotic use fell from 55% (28/51) and
      57% (29/51) in 2000 to 10.5% (2/19) and 5.2% (1/19) in 2002. The total costs
      (excluding antibiotics, staffing and surgery) for those treated with Silvazine
      were US$ 109,357 and those treated with Acticoat were US$ 78,907, demonstrating a
      saving of US$ 30,450 with the new treatment. The average length of stay (LOS) in
      hospital was 17.25 days for the Silvazine group and 12.5 days for the Acticoat
      group-a difference of 4.75 days. These audits demonstrate that Acticoat results
      in a reduced incidence of burn wound cellulitis, antibiotic use and overall cost
      compared to Silvazine in the treatment of early burn wounds.

PMID- 15993303
TI  - Should dermal scald burns in children be covered with autologous skin grafts or
      with allogeneic cultivated keratinocytes?--"The Viennese concept".
AB  - The treatment of scald burns in children is still under discussion. The aim of
      the present study was to evaluate an optimised treatment regime for scald burns
      in children. Between 1997 and 2002, 124 children underwent surgical intervention
      due to burn injuries. Thirty-six out of these 124 children were enrolled into the
      evaluation of our recent treatment protocol. Twenty-two children with scald burns
      covering an average body surface area (TBSA) of 18.5% were treated by early
      excision and coverage with allogeneic keratinocytes in case of partial thickness
      lesions (keratinocyte group). Fourteen children with a TBSA of 17.2% were treated
      with autologous skin grafts alone (skin graft group). Both groups were comparable
      according to age, burn depth and affected TBSA. The complete clinical follow-up
      examination of at least 17 months was performed in 12 out of 22 children of the
      keratinocyte group and in 9 out of 14 patients of the comparative group. Visible
      scar formations were classified according to the Vancouver Scar Scale (VSS) in
      each patient. The use of allogeneic keratinocytes led to complete
      epithelialisation within 12 days in 20 of the 22 cases. No secondary skin
      grafting procedures had to be done. Skin take rate at the sixth postoperative day
      was 100% in the skin graft group. Blood transfusions were administered
      intraoperatively according to the clinical need of the patients by the
      responsible anaesthesiologist. The mean volume of blood, which had to be
      transfused was 63.9 ml in the keratinocyte group and significantly lower than the
      volume of 151.4 ml, which was administered in the skin graft group (p=0.04). At
      follow up the VSS observed in areas covered by keratinocytes was 2.33 on the
      average and therefore, significantly lower than the VSS of 5.22 in skin grafted
      areas of the comparative group (p=0.04). In children the use of cultivated
      keratinocytes in partial thickness scald burns is a procedure, which renders
      constantly reliable results. It minimizes the areas of autologous skin harvesting
      and reduces the amount of blood transfusions. The fact that less scarring is
      observed after keratinocyte grafting leads to the conclusion that skin grafting
      in children should be restricted to scalded areas, which have to be excised to
      the subcutaneous fat tissue.

PMID- 15993302
TI  - The relative thermal stability of tissue macromolecules and cellular structure in
      burn injury.
AB  - When tissue is subjected to higher than physiological temperatures, protein and
      cell organelle structures can be altered resulting in cell death and subsequent
      tissue necrosis. A burn injury can be stratified into three main zones,
      coagulation, stasis and edema, which correlate with the extent of heat exposure
      and thermal properties of the tissue. While there has been considerable effort to
      characterize the time-temperature dependence of the injury, relatively little
      attention has been paid to the other important variable, the thermal
      susceptibility of the tissue. In the present study, we employ a standard physical
      chemistry approach to predict the level of denaturation at supraphysiological
      temperatures of 12 vital proteins as well as RNA, DNA and cell membrane
      components. Melting temperatures and unfolding enthalpies of the cellular
      components are used as input experimental parameters. This approach allows us to
      establish a relation between the level of denaturation of critical cellular
      components and clinical manifestations of the burn through the characteristic
      zones of the injury. Specifically, we evaluate the degree of molecular alteration
      for characteristic temperature profiles at two different depths (Mid-Dermis and
      Dermis-Fat interface) of 80 degrees C; 20s contact burn. The results of this
      investigation suggest that the thermal alteration of the plasma membrane is
      likely the most significant cause of the tissue necrosis. The lipid bilayer and
      membrane-bound ATPases show a high probability of thermal damage (almost 100% for
      the former and 85% for the latter) for short heat exposure times. These results
      suggest that strategies to minimize the damage in a burn injury might focus on
      the stabilization of the cellular membrane and membrane-bound ATPases. Further
      work will be required to validate these predictions in an in vivo model.

PMID- 15993304
TI  - Treatment of second degree facial burns with allografts--preliminary results.
AB  - Facial burns are very common and have significant clinical impact. However, the
      treatment regimen for superficial to deep facial burns is not well defined. The
      purpose of this study was to investigate the effects of cadaver skin grafting in
      deep partial thickness facial burns in comparison to standard care. In a
      prospective open study design severely injured patients with superficial and deep
      partial thickness burns were randomized into the group receiving open treatment
      with silversulfadiazine (standard n=5) or into the group receiving early
      superficial debridement followed by coverage with glycerolized cadaver skin
      (n=5). The outcome measures were time and quality of wound healing, and incidence
      of hypertrophic scarring at 3 and 6 months post burn. There were no significant
      differences in demographics between groups. In the group treated with the
      allogenic material time to reepithelialization was 10.5 days, while it was 12.4
      days in the silversulfadiazine group (p<0.05). Scar quality was found to be
      significantly improved in the allogenic treatment group. Three and 6 months
      postburn there were no patients with significant hypertrophic scarring in the
      allogenic group while there were two patients who developed hypertrophic scars in
      the silversulfadiazine group (p<0.05). In this study, we demonstrated that
      glyzerolized cadaver allograft skin represents a superior biological dressing for
      shallow and deep partial thickness facial burns. This is in concordance with
      other reports on scalds. It would be worthwhile to perform more clinical studies
      with a larger number of patients to further evaluate the effect and function of
      allogenic skin for facial burns.

PMID- 15993305
TI  - Effects of heparin on bacterial translocation and gut epithelial apoptosis after
      burn injury in the rat: dose-dependent inhibition of the complement cascade.
AB  - This study investigated levels of complement inhibition, apoptosis of gut
      epithelium, and bacterial translocation (BT) associated with different doses of
      heparin in rats with severe burns. After burn injury, the animals in Groups 1, 2,
      3, and 4 received intravenous tail-vein bolus heparin doses of 150, 300, 600, and
      1200 U/kg, respectively. Group 5 received no heparin after burn injury. Group 6
      served as control group. According to the results, Group 2 had the highest rate
      of positive staining for C3, and Group 4 had the lowest rate. There were
      significant differences between these two groups with respect to distribution of
      immunoflouresein scores for C3 (p=0.01). Group 5 had the highest mean TUNEL index
      of all the groups (258/10) (p=0.01). On electron microscopy, the connective
      tissue cells in the ileal submucosa from Groups 4 and 5 showed more significant
      apoptotic changes than the corresponding cells in the other groups. The total BT
      values in Group 4 (129 x 10(4) CFU) and Group 5 (100 x 10(4) CFU) were both
      significantly higher than those in the other groups (p=0.01). Group 1 had the
      lowest total BT value (6.1 x 10(2) CFU) (p=0.001). In summary, our results
      confirm that heparin administration after significant burn injury in rats can
      reduce BT, and that the effect is related to dose. The findings also indicate
      that levels of BT after burn injury increase in parallel with the extent of gut
      epithelial cell apoptosis.

PMID- 15993306
TI  - Prevalence of hypertrophic scar formation and its characteristics among the
      Chinese population.
AB  - Each year in Hong Kong, about 350,000 surgical procedures are conducted for
      various types of conditions. Previous review indicated that the prevalence of
      hypertrophic scar among Caucasians ranged from 15% to 63% and that the incidence
      was even higher among non-Caucasians. This study aims to find out the prevalence
      rate of hypertrophic scar among the Hong Kong Chinese population after
      standardized surgical procedures. A systematic and objective scar measurement
      protocol is implemented in this study. The spectrocolorimeter, Miniscan XE plus
      was used to measure the scar pigmentation based on the theory of the CIE colour
      model. The tissue ultrasound palpation system (TUPS) was employed to measure scar
      thickness. From May 2001 to December 2003, 154 patients, who received surgical
      intervention at the Department of Orthopaedics and Traumatology of a large
      regional hospital, were invited to join a scar-screening test. One hundred and
      fifteen patients (74.67%) were found to have signs of hypertrophic scar based on
      thickness, pliability, pigmentation and vascularity (using the Vancouver scar
      scale (VSS) score). One hundred and one patients consented to have more
      comprehensive scar assessment. Results indicated that the scar thickness was
      4.91+/-1.03 mm. Compared with the adjacent normal skin, the color of hypertrophic
      scar was significantly different in terms of lightness (d.f.=100, t=-19.36,
      p<0.01), redness (d.f.=100, t=15.75, p<0.01) and yellowness (d.f.=100, t=-11.48,
      p<0.01) using paired t-test analysis. Fourtysix point five percent and 33.7%
      among patients reported pain (2.19+/-2.74) and itchiness (1.47+/-2.53) over the
      scar. The objective scar assessments showed that more than 70% of scars had
      increase in thickness and pigmentation after surgery. More than 40% of patients
      reported pain and itchiness. The results showed that more than 70% of the scars
      in the HK Chinese population had become hypertrophic in terms of pigmentation,
      thickness and physical symptoms such as pain and itchiness 1 month after the
      surgical intervention. More long-term follow up study should be done to find out
      the prevalence and that it is essential to provide early intervention before the
      scar becomes problematic in management.

PMID- 15993307
TI  - Reconstruction of deep cubital fossa defects with exposure of brachial artery due
      to high tension electrical burns and treatment algorithm.
AB  - In this paper, we selected eight patients who had cubital fossa electrical burns
      with exposure or damage of the brachial artery, during the period 2000 to 2004
      and formulated an algorithm to salvage upper limbs. We demonstrated the
      effectiveness of the algorithm to rescue the extremity from amputation and to
      restore the functional ability combined with coverage of the defects. After
      initial management with decompression and debridement of the nonviable tissues
      surrounding the brachial artery, we used local fasciocutaneous flaps or pedicled
      latissimus dorsi (LD) muscle/musculocutaneous flaps immediately to cover and also
      to avoid the perforation of this artery with a mean of 5.5 operations and with an
      amputation rate of 12.5%. When perforation or necrotic focus was seen on the
      arterial wall without viable tissue around the brachial artery, circulation was
      restored with vein grafts. Deep defects in the cubital fossa with exposure of the
      brachial artery should be covered with well-vascularized tissue as soon as
      possible after serial debridements. If the necrotic focus is seen on the wall of
      the artery, it often requires a venous graft with flap coverage. In the presence
      of viable tissue around the artery, however, fasciocutaneous flaps are useful and
      they reduce the operation time and duration of hospital stay. We treated deep
      defects with exposure of the brachial artery in the cubital fossa according to
      our established algorithm. Adherence to this approach precluded dilemmas in the
      selection of flap types for the management of bulky tissue defects.

PMID- 15993308
TI  - Inhibitory effects of sasanquasaponin on over-expression of ICAM-1 and on
      enhancement of capillary permeability induced by burns in rats.
AB  - The purpose of this study was to investigate the effects of sasanquasaponin (SQS)
      on ICAM-1 expression and capillary permeability induced by burns in rats. Male
      adult Sprague-Dawley (SD) rats were subjected to burns in the presence or absence
      of SQS, and then intravenously injected with Evans blue (60.0 mg/kg body weight).
      The levels of soluble ICAM-1 (sICAM-1) in sera were assayed using ELISA and the
      expression levels of transmembrane ICAM-1 (mICAM-1) in aorta were determined by
      Western blots and ICAM-1 mRNA levels were measured using semi-quantification RT
      PCR. The capillary permeability was determined spectrophotometrically. The
      results showed that SQS markedly lowered the levels of sICAM-1 in sera, and
      considerably inhibited the over-expression as well as transcription of mICAM-1 in
      rat aorta. In addition, SQS dramatically inhibited the enhancement of dermal
      capillary permeability induced by burns in a dose-dependent manner. These results
      suggest that SQS, developed from Chinese traditional herbs, might be effective in
      decreasing inflammation induced by burns.

PMID- 15993309
TI  - The use of adipofascial turnover flaps for coverage of complex dorsal ring finger
      defects caused by electric burns.
AB  - This paper describes a unique occupational electrical injury that results in a
      complex defect on the dorsal aspect of the ring finger. The injury was seen in
      seven electricians working while wearing a ring on the ring finger. All patients
      were treated successfully using random adipofascial turnover flaps. The electric
      current was found to cause a zone of subcutaneous necrosis adjacent to the skin
      burn. This zone of subcutaneous necrosis varied in size but never exceeded 5mm
      and it was easy to recognize the extent of this zone intraoperatively because of
      the presence of the thrombosed dorsal subcutaneous veins within the necrotic
      subcutaneous tissue. These observations suggested that adequate debridement and
      then location of the base of the adipofascial flap proximal to the edge of the
      debrided area was an appropriate procedure. Other technical considerations were
      described to ensure a successful outcome. It was concluded that adipofascial
      turnover flaps were not only reliable in these electrical injuries, but also had
      several advantages when compared with other flaps commonly used to reconstruct
      dorsal digital defects.

PMID- 15993310
TI  - A portable, universal patient positioning and holding system for use in the burn
      patient 'The Burnwalter'.
AB  - A technique is described for the intra-operative positioning of the burn patient,
      which allows circumferential access without the need for specialized equipment or
      extra personnel. The equipment is available in any standard operating room and
      table without the need for redesign or new construction. In addition, it allows
      full 360 degrees access and eliminates the need for extra personnel to hold
      proper positioning. This allows for more efficient operating and should minimize
      the unwanted sequelae of hypothermia and blood loss. Operating time may be
      decreased and the patient may require less operative procedures. The same or more
      work can be done by less personnel, in less time, with no added cost.

PMID- 15993311
TI  - Orbital cellulitis in a burned child.

PMID- 15993312
TI  - Simultaneous use of two flaps for granulating area with extension contracture of
      elbow.

PMID- 15993313
TI  - Biobrane in bairns with burns and bugs?

PMID- 15993314
TI  - Tattoos: a confounding issue in laser Doppler imaging of burn depth.

PMID- 15993315
TI  - Extensive thrombosis of the inferior vena cava and portal vein following
      electrical injury.

PMID- 15993316
TI  - Danger of being second victim when resuscitating chemically burned patient.

PMID- 15993317
TI  - Serum creatinine kinase levels for diagnosing muscle damage in electrical burns.

PMID- 15993318
TI  - Effects of seizures on brain development: lessons from the laboratory.
AB  - Both clinical and laboratory studies demonstrate that seizures early in life can
      result in permanent behavioral abnormalities and enhance epileptogenicity. In
      experimental rodent models, the consequences of seizures are dependent upon age,
      etiology, seizure duration, and frequency. Recurrent seizures in immature rats
      result in long-term adverse effects on learning and memory. These behavioral
      changes are paralleled by changes in brain connectivity, dendritic morphology,
      excitatory and inhibitory receptor subunits, ion channels, and neurogenesis.
      These changes can occur in the absence of cell loss. Although impaired cognitive
      function and brain changes have been well documented after early onset seizures,
      the mechanisms of seizure-induced injury remain unclear. Recent studies have
      demonstrated abnormalities in single cell function that parallel behavioral
      changes.

PMID- 15993319
TI  - Validation of two rating scales for attention-deficit hyperactivity disorder
      diagnosis in Colombian children.
AB  - This study assesses the validity of the Behavioral Assessment System for Children
      parent and teacher questionnaires for attention-deficit hyperactivity disorder
      diagnosis in a randomized sample of 344 Colombian children (145 cases, 199
      controls), males and females, ages 6 to 11, with an estimated Wechsler Full Scale
      Intelligence Quotient over 70. The assessment protocol for both groups included
      psychiatric, neurologic, and psychological interviews, parent and teacher rating
      forms, and an Attention-Deficit Hyperactivity Disorder Checklist. All Behavioral
      Assessment System for Children-parent and teacher dimensions, except withdrawal
      and somatization, significantly differentiated cases and controls. Parents and
      teachers rated attention-deficit hyperactivity disorder combined type children as
      significantly more aggressive. Both questionnaires had good discriminant accuracy
      for detecting cases and control children, but accuracy for discriminating between
      attention-deficit hyperactivity disorder subtypes was poor. The Behavioral
      Assessment System for Children-parent and teacher questionnaires for 6- to 11
      year-olds may be useful tools for diagnosing the presence of attention-deficit
      hyperactivity disorder. Additional assessment methods will be needed to
      discriminate between the subtypes.

PMID- 15993320
TI  - Neurodevelopmental outcome in children with posthemorrhagic hydrocephalus.
AB  - To determine the factors affecting the neurodevelopmental outcome in children
      with posthemorrhagic hydrocephalus, 78 children with intraventricular hemorrhage
      grade 3 or 4 were analyzed concerning the outcome in relation to the grade of
      intraventricular hemorrhage and intervention (surgical, medical, or no
      intervention) by means of a follow-up study. The mean age of the subjects at the
      last follow-up was 9.8 years. In children with intraventricular hemorrhage grade
      4 with parenchymal hemorrhage, the outcomes in the group not requiring
      intervention were better than those in the groups requiring intervention, whereas
      in children with intraventricular hemorrhage grade 3 without parenchymal
      hemorrhage, there were no differences in the outcomes among the three groups with
      and without intervention. For the subjects who had undergone the same
      intervention, the outcomes in children with intraventricular hemorrhage grade 4
      were worse than those in children with intraventricular hemorrhage grade 3. The
      outcomes in the children with surgical intervention only correlated with the
      grade of intraventricular hemorrhage. From these findings, we concluded that the
      outcomes in children with posthemorrhagic hydrocephalus were far more affected by
      the existence or extent of parenchymal hemorrhage than by the hydrocephalic
      process, which was suggested to be effectively controlled by the intervention.

PMID- 15993321
TI  - Magnetic resonance imaging in neonatal nonketotic hyperglycinemia.
AB  - This report presents two neonates with nonketotic hyperglycinemia in whom
      conventional magnetic resonance imaging revealed structural cerebral
      abnormalities, diffusion-weighted imaging indicated abnormalities of myelinated
      white matter, and magnetic resonance spectroscopy provided biochemical evidence
      of elevated cerebral glycine levels. The early use of combined magnetic resonance
      modalities in these severely affected infants helped in prognostication and
      clinical management.

PMID- 15993322
TI  - Basilar meningitis associated with ethmoid and sphenoid cephaloceles.
AB  - Nontuberculous causes of basilar meningitis are rare. This study presents the
      case of a male who developed fever and meningitis caused by Streptococcus
      pneumoniae. He developed multiple cranial nerve palsies and imaging findings
      consistent with basilar meningitis and ventriculitis. Computed tomographic scans
      of the floor of the anterior fossa were performed after the detection of a
      cephalocele on magnetic resonance imaging. This imaging revealed a defect in the
      cribiform plate and fovea ethmoidalis with a large nasoethmoidal cephalocele.
      There was a second separate defect and cephalocele involving the middle cranial
      fossa. The association of basilar meningitis with an atypical organism should
      lead to a careful search for disruption in the floor of the anterior or middle
      cranial fossa.

PMID- 15993323
TI  - Stroke-like episode involving a cerebral artery in a patient with MELAS.
AB  - This report describes a patient with mitochondrial myopathy, encephalopathy,
      lactic acidosis, and stroke-like episodes who exhibited a segmental vascular
      narrowing in the crural segment of the right posterior cerebral artery by
      magnetic imaging angiography in the acute phase of the first stroke-like episode.
      The vascular stenosis almost improved on the subsequent neuroimaging study. This
      result suggested that major cerebral arteries might be occasionally involved in a
      stroke-like episode in MELAS (mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes).

PMID- 15993324
TI  - Rapidly progressive spinal muscular atrophy in an ambulatory 2-year-old male.
AB  - A 2-year 9-month-old male was referred for gait disturbances. Main complaints
      were abnormal gait with frequent falls observed as soon as he began to walk
      unaided, at 18 months of age. The first neurologic examination revealed symmetric
      and proximal weakness in the lower limbs with difficulty running and walking
      upstairs. Deep tendon reflexes were decreased, and generalized hypotonia was
      observed. Three months later, at 3 years of age, he had lost independent gait,
      and 1 month later he could not stand unaided. DNA analysis revealed homozygous
      deletion in exons 7 and 8 of SMN1 gene, confirming the diagnosis of spinal
      muscular atrophy. According to the current classification, this patient would be
      classified as spinal muscular atrophy type III. The distinctive feature of this
      case was the short time elapsed (18 months) between onset of spinal muscular
      atrophy and the age at which he lost ambulation. This patient reinforces the
      notion that late onset of symptoms in spinal muscular atrophy and acquisition of
      independent gait do not exclude a rapidly progressive motor deterioration, which
      is important when talking with families about outcome. In those rapidly
      progressive cases, when promptly available, testing for SMN1 gene will prevent
      unnecessary, invasive, or uncomfortable procedures such as lumbar puncture,
      electromyography, or spinal cord magnetic resonance imaging.

PMID- 15993326
TI  - Reducing risks of hospital acquired hyponatremia.

PMID- 15993328
TI  - Pyridoxine-dependent seizures and microcephaly.

PMID- 15993329
TI  - Oxidative stress during the chronic phase after stroke.
AB  - Stroke is a complex disease originating and developing on the background of
      genetic predisposition and interaction between different risk factors that
      chronically damage blood vessels. The search for an effective treatment of stroke
      patients is the main priority of basic and clinical sciences. The chronic phase
      of stroke provides possibilities for therapy directed toward stimulation of
      recovery processes as well as prophylaxis, which reduces the probability of
      subsequent cerebrovascular events. Oxidative stress is a potential contributor to
      the pathophysiological consequences of stroke. The aim of the present review is
      to summarize the current knowledge of the role of oxidative stress during the
      chronic phase after stroke and its contribution to the initiation of subsequent
      stroke. The relationship among inflammation, hemostatic abnormalities, and
      platelet activation in chronic stroke patients is discussed in the context of
      ongoing free radical processes and oxidative damage. Free radical-mediated
      effects of increased plasma level of homocysteine and its possible contribution
      to the processes leading to recurrent stroke are discussed as well. The status of
      the antioxidant defense system and the degree of oxidative damage in the
      circulation of stroke survivors are examined. The results are interpreted in view
      of the effects of the vascular risk factors for stroke that include additional
      activation of inflammatory and free radical mechanisms. Also, the possibilities
      for combined therapy including antioxidants in the acute and convalescent stages
      of stroke are considered. Future investigations are expected to elucidate the
      role of free radical processes in the chronic phase after stroke and to evaluate
      the prophylactic and therapeutic potential of anti-radical agents.

PMID- 15993330
TI  - Methamphetamine-enhanced embryonic oxidative DNA damage and neurodevelopmental
      deficits.
AB  - Methamphetamine (METH) causes dopaminergic nerve terminal degeneration and
      functional deficits in adult mice, but its neurodevelopmental effects are
      unclear. We investigated METH-initiated oxidative DNA damage in brain during the
      embryonic and fetal periods, and the postnatal histological and functional
      consequences. Pregnant CD-1 mice were treated with a single dose of METH (20 or
      40 mg/kg ip) or its saline vehicle on Gestational Day 14 or 17. METH enhanced
      conceptal DNA oxidation, determined by 8-oxoguanine formation, in brain and liver
      by at least 2-fold at 1 h (P < 0.05), and more so in some fetal brains at 4 h.
      After birth, motor coordination on the rotarod apparatus in the METH-exposed
      offspring was impaired for at least 12 weeks (P < 0.05). Unlike in adults, this
      postnatal functional deficit in offspring exposed in utero to METH was not
      associated with degeneration of striatal dopaminergic nerve terminals at 12 weeks
      of age determined by tyrosine hydroxylase staining, suggesting a novel
      pathological mechanism in utero. This is the first evidence of oxidative DNA
      damage in embryonic and fetal brain caused by amphetamines, leading to long-term
      postnatal neurodevelopmental deficits via a mechanism different from that
      underlying the neurodegeneration observed in METH-exposed adults.

PMID- 15993331
TI  - On the specificity of 4-amino-5-methylamino-2',7'-difluorofluorescein as a probe
      for nitric oxide.
AB  - The specificity of 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) for
      nitric oxide was evaluated in in vitro systems. The probe was found fairly
      specific for nitric oxide. Potential sources of artifacts include the
      autoxidation of DAF-FM, potentiated by light, and its oxidation by sources of
      superoxide and peroxyl radicals, leading to fluorescence spectra
      indistinguishable from those of the nitric oxide adduct. Although DAF-FM reacts
      with peroxynitrite, this reaction seems to be of secondary importance under quasi
      physiological conditions. On the other hand, a simultaneous presence of a nitric
      oxide source and a superoxide or hydrogen peroxide decreases or increases the
      fluorescence of DAF-FM, respectively, resulting in biased estimates of nitric
      oxide production.

PMID- 15993332
TI  - Paraoxonases (PONs) 1, 2, and 3 are expressed in human and mouse gastrointestinal
      tract and in Caco-2 cell line: selective secretion of PON1 and PON2.
AB  - The paraoxonase (PON) family contains three genes (PON1/2/3) that are believed to
      be involved in the protection against oxidative stress. PON1 and PON3 are
      circulating in serum attached to high-density lipoprotein fraction (HDL), whereas
      PON2 is ubiquitously expressed. The intestine is the second major organ that
      synthesizes lipoproteins; therefore, we examined PON mRNA expression and protein
      levels in gastrointestinal biopsies from humans, from C57BL6 mice, and from Caco
      2 cells, a colon carcinoma-derived cell line that exhibits properties of
      intestinal epithelium at differentiation. PON 1/2/3 mRNA and proteins were
      present in human biopsies with variable expression among different
      gastrointestinal segments. Only PON2 and PON3 were present in mice. All PON mRNA,
      proteins, and enzymatic activities were present in Caco-2 cells. Oxidation of
      CaCo-2 cells with ferrum ascorbate had no significant effect on PON mRNA
      expression, but it increased paraoxonase and lactonase activity, whereas
      statinase activity was decreased. We showed polarized secretion of PON1
      (basolateral) and PON2 (apical) into Caco-2 culture medium, raising the
      possibility that intestine is capable of producing and releasing PON1 and PON3 to
      the circulation, whereas PON2 is released at the brush-border membrane to
      intestinal lumen where it may perform another yet unclear function.

PMID- 15993333
TI  - Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by
      glutathione disulfide in neuroblastoma cells.
AB  - Changes in intracellular redox status are crucial events that trigger downstream
      proliferation or death responses through activation of specific signaling
      pathways. Moreover, cell responses to oxidative challenge may depend on the
      pattern of redox-sensitive molecular factors. The stress-activated protein
      kinases c-Jun-N-terminal kinase (JNK) and p38 MAP kinase (p38MAPK) are implicated
      in different forms of apoptotic neuronal cell death. Here, we investigated the
      effects, on neuroblastoma cells, of the prooxidant molecule GSSG, which we
      previously demonstrated to be an efficient proapoptotic compound able to activate
      the p38MAPK death pathway in promonocytic cells. We found that neuroblastoma
      cells are not prone to GSSG-induced apoptosis, although the treatment slightly
      induced growth arrest through the accumulation of p53 and its downstream target
      gene, p21. However, GSSG treatment became cytotoxic when cells were previously
      depleted of intracellular GSH content. Under this condition, apoptosis was
      triggered by an increased production of superoxide that led to a specific
      activation of the JNK-dependent pathway. The involvement of superoxide and JNK
      was demonstrated by cell death inhibition in experiments carried out in the
      presence of Cu,Zn superoxide dismutase or with specific inhibitors of JNK
      activity. Our data give support to the studies that indicate preferential
      requirements for the involvement of stress-activated kinases in apoptotic
      neuronal cells.

PMID- 15993335
TI  - Dynamic changes in reactive oxygen species and antioxidant levels in retinas in
      experimental glaucoma.
AB  - We investigated the balance of free radicals in retinas at various time points
      after chronically elevating intraocular pressures in rats. The left eyes of
      female Wistar rats were divided into five intraocular pressure elevation (IOPE)
      subgroups after cauterization of three episcleral veins (1 day, 3 days, 1 week, 3
      weeks, and 5 weeks) and time-related sham controls. Chemiluminescence levels were
      examined in isolated retinas. The nitroblue tetrazolium (NBT) incubation method
      was also performed to confirm the superoxide expression. The activities of
      antioxidant enzymes and lipid peroxides in isolated retinas were detected by
      spectrophotometry. In the IOPE group, the intraocular pressure after
      cauterization was around 22-30 mm Hg; chemiluminescence levels of isolated
      retinas were significantly elevated on day 3 and week 1; there were more NBT
      positive retinal ganglion cells on day 1 and day 3; lipid peroxidation also
      increased significantly from day 1 and came back to the baseline on week 5; the
      activities of superoxide dismutases and catalase rose on week 1. Intraocular
      pressure elevation was shown to change the free radical balance. We suggest that
      free radicals and their oxidative stresses may play a role in the early stage of
      glaucoma in causing retinal ganglion cell death in our rat model.

PMID- 15993334
TI  - HNE increases HO-1 through activation of the ERK pathway in pulmonary epithelial
      cells.
AB  - Heme oxygenase-1 (HO-1) is a key cytoprotective enzyme and an established marker
      of oxidative stress. Increased HO-1 expression has been found in the resident
      macrophages in the alveolar spaces of smokers. The lipid peroxidation product 4
      hydroxynonenal (HNE) is also increased in the bronchial and alveolar epithelium
      in response to cigarette smoke. This suggests a link between a chronic
      environmental stress, HNE formation, and HO-1 induction. HNE is both an agent of
      oxidative stress in vivo and a potent cell signaling molecule. We hypothesize
      that HNE acts as an endogenously produced pulmonary signaling molecule that
      elicits an adaptive response culminating in the induction of HO-1. Here we
      demonstrate that HNE increases HO-1 mRNA, protein, and activity in pulmonary
      epithelial cells and identify ERK as a key pathway involved. Treatment with HNE
      increased ERK phosphorylation, c-Fos protein, JNK phosphorylation, c-Jun
      phosphorylation, and AP-1 binding. Whereas inhibiting the ERK pathway with the
      MEK inhibitor PD98059 significantly decreased HNE-mediated ERK phosphorylation, c
      Fos protein induction, AP-1 binding, and HO-1 protein induction, inhibition of
      the ERK pathway had no effect on HNE-induced HO-1 mRNA. This suggests that ERK is
      involved in the increase in HO-1 through regulation of translation rather than
      transcription.

PMID- 15993336
TI  - Proliferation dynamics in cultured skin fibroblasts from Down syndrome subjects.
AB  - With a view to better understanding the role of oxidant/antioxidant variables in
      proliferation dynamics of somatic cells, we explored the relationships among
      superoxide dismutase (SOD) activity, glutathione peroxidase (Gpx) activity,
      reactive oxygen intermediates (ROI), and indices of cellular proliferation and
      senescence in cultured fibroblasts from Down syndrome and normal donors. We found
      that Down syndrome cells had a significantly slower proliferative rate, but
      attain replicative senescence at similar population doubling (PD) as control
      cells. Irrespective of donor origin, the number of PD until replicative
      senescence was positively correlated with Gpx activity (r = 0.784, P = 0.007). In
      addition, the presence of exogenous catalase in the growth medium significantly
      extended the number of PD until replicative senescence (P = 0.011). The loss of
      telomere repeats per PD was not different between Down syndrome cells and
      controls. However, SOD activity was inversely correlated with the loss of
      telomere repeats per PD. Collectively, these findings suggest that replicative
      senescence ultimately relates to mechanisms downstream to SOD (i.e., Gpx and
      catalase) and confirmed previous observations about inverse relationships between
      SOD activity and telomere repeat loss per cellular replication.

PMID- 15993337
TI  - Differential effects of diabetes on the expression of the gp91phox homologues
      nox1 and nox4.
AB  - The nox2-dependent NADPH oxidase was shown to be a major superoxide source in
      vascular disease, including diabetes. Smooth muscle cells of large arteries lack
      the phagocytic gp91phox subunit of the enzyme; however, two homologues have been
      identified in these cells, nox1 and nox4. It remained to be established whether
      also increases in protein levels of the nonphagocytic NADPH oxidase contribute to
      increased superoxide formation in diabetic vessels. To investigate changes in the
      expression of these homologues, we measured their expression in aortic vessels of
      type I diabetic rats. Eight weeks after streptozotocin treatment, we found a
      doubling in nox1 protein expression, while the expression of nox4 remained
      unchanged. This was associated with a significant increase in the NADPH oxidase
      activity in membrane fractions of diabetic heart and aortic tissue. Furthermore,
      we observed a decreased sensitivity of diabetic vessels to acetylcholine and
      nitroglycerin and a decrease in both acetylcholine-stimulated NO production and
      phosphorylation of VASP, despite an increase in endothelial NO synthase (NOSIII)
      expression. In addition, xanthine oxidase activity was markedly increased in
      plasma and 100,000 g supernatant of cardiac tissue of diabetic rats, while
      myocardial mitochondrial superoxide formation was only weakly enhanced. We
      conclude that in addition to phagocytic NADPH oxidase, also nonphagocytic,
      vascular NADPH oxidase subunit nox1, uncoupled NOSIII, and plasma xanthine
      oxidase contribute to endothelial dysfunction in the setting of diabetes
      mellitus.

PMID- 15993338
TI  - Copper chaperone for Cu,Zn-SOD supplement potentiates the Cu,Zn-SOD function of
      neuroprotective effects against ischemic neuronal damage in the gerbil
      hippocampus.
AB  - In the present study, we investigated the chronological alterations in SOD1 and
      its copper chaperone (chaperone for superoxide dismutase, CCS) immunoreactivities
      and their neuroprotective effects against neuronal damage in the gerbil
      hippocampus after 5 min of transient forebrain ischemia. SOD1 and CCS
      immunoreactivities were significantly increased in the stratum pyramidale of the
      CA1 region at 24 and 12 h after ischemic insult, respectively. At 24 h after
      ischemic insult, the SOD1 and CCS immunoreactivities were colocalized in the CA1
      pyramidal cells of the stratum pyramidale. Thereafter, their immunoreactivities
      were significantly decreased in the CA1 region. To elucidate the effects of CCS
      or CCS/SOD1, we constructed the expression vectors PEP-1-SOD and PEP-1-CCS. In
      the CCS-treated group and the CCS/SOD1-treated group, 43.9 and 78.9% pyramidal
      cells, respectively, compared to the sham-operated group, were stained with
      cresyl violet 5 or 7 days after ischemic insult. The distribution pattern of
      active astrocytes and microglia in the PEP-CCS/SOD1-treated group 5 days after
      ischemic insult was similar to that of the sham-operated group. In addition, the
      SOD activity in the PEP-CCS- or PEP-CCS/SOD1-treated group was maintained by 10
      days after ischemic insult. The SOD activity was higher in the PEP-CCS/SOD1
      treated group vs the CCS-treated group. These results suggest that the enhanced
      expression of SOD1 and CCS may be related to compensatory mechanisms against
      ischemic damage and that cotreatment with CCS and SOD1 has a greater
      neuroprotective effect than treatment with CCS or SOD1 in isolation.

PMID- 15993339
TI  - Desferal inhibits breast tumor growth and does not interfere with the tumoricidal
      activity of doxorubicin.
AB  - Desferal is a clinically approved iron chelator used to treat iron overload.
      Doxorubicin is an anthracycline cancer chemotherapy drug used in the treatment of
      breast cancer. It can undergo redox cycling in the presence of iron to produce
      reactive oxygen species. The oxidant-generating activity of doxorubicin is
      thought to be responsible for the cardiotoxic side effects of the drug, but it is
      unclear whether it is also required for its anti-tumor activity. To test whether
      an iron-chelating antioxidant would interfere with the tumor-killing activity of
      doxorubicin, nude mice were transplanted with xenografts of human breast cancer
      MDA-MB 231 cells and then treated with doxorubicin and/or desferal. Not only did
      desferal not interfere with the anti-tumor activity of doxorubicin, it inhibited
      tumor growth on its own. In vitro studies confirmed that desferal inhibits breast
      tumor growth. However, it did not induce apoptosis, nor did it induce cell cycle
      arrest. Instead, desferal caused cytostasis, apparently through iron depletion.
      The cytostatic activity of desferal was partially ameliorated by pretreatment
      with iron-saturated transferrin, and transferrin receptor expression on breast
      cancer cells nearly doubled after exposure to desferal. In contrast to its effect
      on tumor cells, desferal did not inhibit growth of normal breast epithelial
      cells. The data indicate that the anti-tumor activity of doxorubicin is not
      dependent on iron-mediated ROS production. Furthermore, desferal may have utility
      as an adjunctive chemotherapy due to its ability to inhibit breast tumor growth
      and cardiotoxic side effects without compromising the tumor-killing activity of
      an anthracycline chemotherapy drug.

PMID- 15993340
TI  - Nitric oxide synthase inhibitors in experimental ischemic stroke and their
      effects on infarct size and cerebral blood flow: a systematic review.
AB  - Nitric oxide produced by the neuronal or inducible isoform of nitric oxide
      synthase (nNOS, iNOS) is detrimental in acute ischemic stroke (IS), whereas that
      derived from the endothelial isoform is beneficial. However, experimental studies
      with nitric oxide synthase inhibitors have given conflicting results. Relevant
      studies were found from searches of EMBASE, PubMed, and reference lists; of 456
      references found, 73 studies involving 2321 animals were included. Data on the
      effects of NOS inhibition on lesion volume (mm3, %) and cerebral blood flow (CBF;
      %, ml * min(-1) * g(-1)) were analyzed using the Cochrane Review Manager
      software. NOS inhibitors reduced total infarct volume in models of permanent
      (standardized mean difference (SMD) -0.56, 95% confidence interval (95% CI) 
      0.86, -0.26) and transient (SMD -0.99, 95% CI -1.25, -0.72) ischemia. Cortical
      CBF was reduced in models of permanent but not transient ischemia. When assessed
      by type of inhibitor, total lesion volume was reduced in permanent models by nNOS
      and iNOS inhibitors, but not by nonselective inhibitors. All types of NOS
      inhibitors reduced infarct volume in transient models. NOS inhibition may have
      negative effects on CBF but further studies are required. Selective nNOS and iNOS
      inhibitors are candidate treatments for acute IS.

PMID- 15993341
TI  - Medical wastes characterisation in healthcare institutions in Mauritius.
AB  - This study was initiated to characterize solid and liquid wastes generated in
      healthcare institutions and to provide a framework for the safe management of
      these wastes. The project was carried at three major medical institutions,
      namely, the Jeetoo Hospital, the Sir Seewoosagur Ramgoolam National (SSRN)
      Hospital and the Clinic Mauricienne. A waste audit carried out at these sites
      revealed that approximately 10% of solid wastes was hazardous in nature,
      consisting mainly of infectious, pathological and chemical wastes. The average
      amount of hazardous wastes per patient per day was found to be 0.072 kg at Jeetoo
      hospital, 0.091 kg at SSRN hospital and 0.179 kg at the clinic. The amount of
      hazardous wastes generated as a function of the number of occupied beds was found
      to follow a relationship of type y=0.0006x-0.19, where y was the amount of
      hazardous wastes generated per bed per day and x was the number of occupied beds.
      The waste quantifying process also revealed that at SSRN Hospital, 0.654 m(3) of
      water was being consumed per patient per day and the amount of wastewater
      produced was 500 m(3)/day. Further analysis revealed that the wastewater was
      polluting with chemical oxygen demand (COD), biological oxygen demand (BOD(5)),
      total suspended solids (TSS) and coliform content well above permissible limits.

PMID- 15993342
TI  - Composition and production rate of dental solid waste in Xanthi, Greece:
      variability among dentist groups.
AB  - The objective of this work was to determine the composition and production rate
      of dental solid waste, produced by dental practices in the Prefecture of Xanthi,
      a multicultural area in Northeast Greece with a population of 102,000. For the
      study, 22 private dental practices and 1 public dental practice were selected of
      the 48 private and 5 public dental practices in operation. The 22 private dental
      practices included 16 owned by Christian Greek-born dentists, 3 by Moslem
      dentists and 3 by Christian dentists repatriated from the former Soviet Union.
      Differentiation on the basis of religion is directly related to the countries
      from which dentists received their training, e.g., Greece-European Union, Turkey
      and former Soviet Union. Thus, including the one public dental practice, 4 study
      groups were considered. Waste collection took place for 22 working days, from 20
      May to 27 June 2002. This period was considered to be a representative one for a
      semi-rural area, such as Xanthi. Dentists were instructed to collect the total
      amount of waste they produced. A total of 260 kg dental solid waste was collected
      during the study period and was manually separated. Dental solid waste was
      classified in three main categories: (1) Infectious and potentially infectious
      waste, accounting for 94.7% by weight. (2) Non-infectious waste accounting for
      2.0%. (3) Domestic-type waste, accounting for 3.3% by weight. The category of
      infectious waste is classified as hazardous and includes components containing
      metal (8.51%), components without metal (91.18%) and amalgam (0.33%). Using the
      weight data, the production rate of dental solid waste for the study period in
      the Prefecture of Xanthi was determined to be 513 g/practice/day and of
      infectious and potentially infectious waste 486 g/practice/day. The latter
      includes the production rate of sharps (9.8 g/practice/day), non-sharps (31.6),
      infectious waste without metal (443) and amalgam (1.6 g/practice/day). Since
      dental solid waste is currently disposed of in landfills together with the
      municipal solid waste, the results of the study were used to suggest an
      appropriate management scheme. The results were also used to compare the
      composition and production rates of dental solid waste produced by the 4 study
      groups.

PMID- 15993343
TI  - Biomedical solid waste management in an Indian hospital: a case study.
AB  - The objectives of this study were: (i) to assess the waste handling and treatment
      system of hospital bio-medical solid waste and its mandatory compliance with
      Regulatory Notifications for Bio-medical Waste (Management and Handling) Rules,
      1998, under the Environment (Protection Act 1986), Ministry of Environment and
      Forestry, Govt. of India, at the chosen KLE Society's J. N. Hospital and Medical
      Research Center, Belgaum, India and (ii) to quantitatively estimate the amount of
      non-infectious and infectious waste generated in different wards/sections. During
      the study, it was observed that: (i) the personnel working under the occupier
      (who has control over the institution to take all steps to ensure biomedical
      waste is handled without any adverse effects to human health and the environment)
      were trained to take adequate precautionary measures in handling these bio
      hazardous waste materials, (ii) the process of segregation, collection,
      transport, storage and final disposal of infectious waste was done in compliance
      with the Standard Procedures, (iii) the final disposal was by incineration in
      accordance to EPA Rules 1998, (iv) the non-infectious waste was collected
      separately in different containers and treated as general waste, and (v) on an
      average about 520 kg of non-infectious and 101 kg of infectious waste is
      generated per day (about 2.31 kg per day per bed, gross weight comprising both
      infectious and non-infectious waste). This hospital also extends its facility to
      the neighboring clinics and hospitals by treating their produced waste for
      incineration.

PMID- 15993344
TI  - Medical wastes management in the south of Brazil.
AB  - In developing countries, solid wastes have not received sufficient attention. In
      many countries, hazardous and medical wastes are still handled and disposed
      together with domestic wastes, thus creating a great health risk to municipal
      workers, the public and the environment. Medical waste management has been
      evaluated at the Vacacai river basin in the State of Rio Grande do Sul, Brazil. A
      total of 91 healthcare facilities, including hospitals (21), health centers (48)
      and clinical laboratories (22) were surveyed to provide information about the
      management, segregation, generation, storage and disposal of medical wastes. The
      results about management aspects indicate that practices in most healthcare
      facilities do not comply with the principles stated in Brazilian legislation. All
      facilities demonstrated a priority on segregation of infectious-biological
      wastes. Average generation rates of total and infectious-biological wastes in the
      hospitals were estimated to be 3.245 and 0.570 kg/bed-day, respectively.

PMID- 15993345
TI  - Healthcare waste management: a case study from the National Health Service in
      Cornwall, United Kingdom.
AB  - This paper looks at steps taken towards the development of a 10-year strategy for
      the management of healthcare waste from the National Health Service (NHS) in
      Cornwall, United Kingdom. The major issues and challenges that affect the
      management of waste by the NHS, including its organisational structure and
      collection infrastructure, are outlined. The waste flows of the main acute
      medical site are detailed, using waste audits of domestic and clinical bags,
      redundant equipment, bulky waste, and special waste. Some of the common barriers
      to change, such as staff habits and public perceptions, are also identified.
      Recommendations are made with respect to improvements in the overall
      organisational infrastructure and increased localised control. The
      recommendations also centre around the formation of strategic partnerships,
      within the site, between sites and at the broader level between the NHS and its
      surrounding community. An important challenge to be overcome is the need to
      progress from the concept of "waste management", to one of sustainable decision
      making regarding resource use, including methods of waste minimisation at the
      source and recycling. Staff training and awareness underpin several of the short
      and medium/long term solutions suggested to reduce the waste at the source and
      recover value from that produced. These measures could potentially reduce
      disposal quantities by as much as 20-30% (wt.) and costs by around 25-35%.

PMID- 15993346
TI  - Infectious waste management in Japan: a revised regulation and a management
      process in medical institutions.
AB  - In Japan, the waste management practice is carried out in accordance with the
      Waste Disposal Law of 1970. The first rule of infectious waste management was
      regulated in 1992, and infectious wastes are defined as the waste materials
      generated in medical institutions as a result of medical care or research which
      contain pathogens that have the potential to transmit infectious diseases.
      Revised criteria for infectious waste management were promulgated by the Ministry
      of Environment in 2004. Infectious waste materials are divided into three
      categories: the form of waste; the place of waste generation; the kind of
      infectious diseases. A reduction of infectious waste is expected. We introduce a
      summary of the revised regulation of infectious waste management in this article.

PMID- 15993347
TI  - Alternatives for the treatment and disposal of healthcare wastes in developing
      countries.
AB  - Waste production in healthcare facilities in developing countries has brought
      about a variety of concerns due to the use of inappropriate methods of managing
      the wastes. Inappropriate treatment and final disposal of the wastes can lead to
      adverse impacts to public health, to occupational health and safety, and to the
      environment. Unfortunately, most economically developing countries suffer a
      variety of constraints to adequately managing these wastes. Generally in
      developing countries, few individuals in the staff of the healthcare facility are
      familiar with the procedures required for a proper waste management program.
      Furthermore, the management of wastes usually is delegated to poorly educated
      laborers who perform most activities without proper guidance and insufficient
      protection. This paper presents some of the most common treatment and disposal
      methods utilized in the management of infectious healthcare wastes in developing
      countries. The methods discussed include: autoclave; microwave; chemical
      disinfection; combustion (low-, medium-, and high-technology); and disposal on
      the ground (dump site, controlled landfill, pits, and sanitary landfill). Each
      alternative for treatment and disposal is explained, including a description of
      the types of wastes that can and cannot be treated. Background information on the
      technologies also is included in order to provide information to those who may
      not be familiar with the details of each alternative. In addition, a brief
      presentation of some of the emissions from each of the treatment and disposal
      alternatives is presented.

PMID- 15993348
TI  - Incineration of healthcare wastes: management of atmospheric emissions through
      waste segregation.
AB  - The amount of atmospheric pollutants emitted through the incineration of
      healthcare wastes can be estimated using emission factors. Emission factors have
      been published without including sufficient information about the types of wastes
      incinerated. This paper reports the first emission factors estimated for the
      incineration of wastes segregated into different types according to the
      Portuguese legislation. One controlled-air incinerator without air pollution
      control devices was used in the research. The main objectives of the study were:
      (i) to estimate the emission factors for particulate matter, dioxins, heavy
      metals and gaseous pollutants, according to the type of waste incinerated; (ii)
      to evaluate the quality of atmospheric emissions; and (iii) to define a
      methodology for the management of atmospheric emissions, evaluating the influence
      of type of waste incinerated and of the segregation method used on the emitted
      amounts. It was concluded that: (i) when emission factors are not associated with
      the type of incinerated mixture, the utility of the emission factors is highly
      doubtful; (ii) without appropriate equipment to control atmospheric pollution,
      incineration emissions exceed legal limits, neglecting the protection of human
      health (the legal limit for pollutant concentrations could only be met for NO(x),
      all other concentrations were higher than the maximum allowed: dioxins, 93-710
      times; Hg, 1.3-226 times; CO, 11-24 times; SO(2), 2-5 times; and HCl, 9-200
      times); (iii) rigorous segregation methodologies must be used to minimize
      atmospheric emissions, and incinerate only those wastes that should be
      incinerated according to the law. A rigorous segregation program can result in a
      reduction of the amount of waste that should be incinerated by 80%. A reduction
      in the quantity of waste incinerated results in a reduction on the amounts of
      pollutants emitted: particulate matter, 98%; dioxins, 99.5%; As, Cd, Cr, Mn and
      Ni, respectively, 90%, 92%, 84%, 77% and 92%; Hg and Pb, practically eliminated;
      SO(2) and NO(x), 93%; and CO and HCl, more than 99%.

PMID- 15993349
TI  - Cement-based materials as containment systems for ash from hospital waste
      incineration.
AB  - Waste generation has increased considerably worldwide in the last decades. As a
      consequence, incineration became an alternative for reducing waste volume,
      leading to the generation of ash as a new type of waste. The new cement-ash
      composite systems have been tested for future applications in building materials.
      Having in mind the previous data and scientific reports, the objective of the
      present study is oriented to evaluate the additions of hospital waste ash in
      cement matrices to be potentially used as construction elements. This involved
      the assessment of the effect of the additions (different proportions of ash and
      metal-spiked ash) on the physico-mechanical properties of the building materials
      and the leachability of metals. The experiences show the feasibility of including
      hospital waste ashes in masonry blocks or other similar products.

PMID- 15993350
TI  - Issues and options for the safe destruction and disposal of used injection
      materials.
AB  - It has long been known that the re-use of syringes can cause the spread of
      infections such as HIV and hepatitis. The production of disposable syringes was
      undertaken as a solution to the infection problem. In developing countries,
      however, there has been an unwanted result: the re-use and recycling of
      disposable syringes. One response has been "auto-disable" syringes that lock the
      plug and piston in place after a single use. These types of approaches, however,
      have resulted in greatly increased volumes of used injection materials. This is a
      particular problem in developing countries where contaminated medical wastes find
      their way into municipal garbage where people are known to scavenge and recycle.
      This poses obvious health risks, both in terms of direct exposure and
      environmental contamination. This study of issues and options for the safe
      destruction and disposal of used injection materials was undertaken using
      document analysis was to bring together and summarise approaches to the inter
      related issues of "syringe re-use" and "clinical waste disposal". The authors
      suggest that holistic approaches to syringe use and clinical waste disposal need
      to be utilized in addressing the situation outlined. The focus is on technology
      and procedures that may be adaptable to rural areas in developing countries.

PMID- 15993351
TI  - Markers of endothelial dysfunction in the prediction of coronary artery disease
      in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study.
AB  - Low-density lipoprotein (LDL) oxidation, the immune response it provokes, and
      lipoprotein subclasses measured by nuclear magnetic resonance (NMR) spectroscopy
      have explained some of the enhanced coronary artery disease (CAD) risks in Type 1
      diabetes. We examined whether cellular adhesion molecules further improve CAD
      prediction. Participants were identified from the Epidemiology of Diabetes
      Complications (EDC) cohort, a 10-year prospective study of childhood-onset Type 1
      diabetes. Mean age at baseline was 28 years, and diabetes duration was 19 years.
      CAD incidence was determined by EDC physician-diagnosed angina, confirmed
      myocardial infarction (MI), stenosis > or =50%, ischemic ECG, or
      revascularization. Cases were gender, age, and diabetes duration (+/-3 years)
      matched with the controls. The samples and risk factors used in the analyses were
      identified from the earliest exam prior to incidence in the cases. Sixty cases
      and 72 controls (including 43 pairs) had complete information on all covariates.
      Cox proportional hazard models with backward elimination and conditional logistic
      regression (for paired analyses) were conducted. Separate analyses were conducted
      to examine whether E-selectin related differently to soft (ischemic ECG and
      angina; n=68) or hard (revascularization, MI, and fatal events; n=37) CAD
      endpoints. Mean E-selectin concentration was elevated among cases (P=.0009)
      compared to controls. Adjusting for previously established CAD risk factors, E
      selectin remained an independent predictor of CAD (HR=1.07, 95% Cl=1.01-1.15).
      Multivariable models confirmed the importance of E-selectin as a risk factor of
      soft (HR=1.13, 95% Cl=1.03-1.24; HRs are per standard deviation increase) but not
      hard CAD. Study results suggest that E-selectin may enhance CAD prediction beyond
      traditional risk factors or markers of oxidative stress in Type 1 diabetes.

PMID- 15993353
TI  - Risk factors for heart disease and stroke among diabetic persons, by disability
      status.
AB  - OBJECTIVE: To determine whether disabled diabetic persons have a higher
      prevalence of risk factors for heart disease and stroke than do diabetic persons
      without disability. RESEARCH, DESIGN, AND METHODS: Data were analyzed for
      noninstitutionalized adults in 27 states and the District of Columbia that
      participated in the Behavioral Risk Factor Surveillance System (BRFSS) in 2001
      and/or 2003. Logistic regression analysis was used to estimate the adjusted
      prevalence and odds ratios of disabled diabetic persons, by sociodemographic
      characteristics. The logit form of each model was used to estimate conditional
      marginal probabilities of risk factors for heart disease and stroke among
      diabetic persons, by disability status. RESULTS: Diabetic persons with disability
      were more likely than those without disability to have more risk factors for
      heart disease and stroke, including insufficient leisure-time physical activity
      or inactivity (adjusted prevalence: 75.2% vs. 63.3%; P<.001), obesity (58.9% vs.
      43.3%; P<.001), hypercholesterolemia (52.6% vs. 48.4%; P=.038), and hypertension
      (63.9% vs. 56.6%; P<.001). They were also more likely to have one or more, two or
      more, three or more, and four or more risk factors (97.2% vs. 95.6%, 83.5% vs.
      74.0%, 56.5% vs. 41.1%, and 22.2% vs. 13.6%, respectively; P< or =.005).
      CONCLUSIONS: Diabetic persons with disability are more likely than those without
      disability to have clusters of risk factors for heart disease and stroke. Health
      care guidelines specifically targeting diabetic patients with disability may be
      needed to aid health care providers in addressing these risk factors.

PMID- 15993352
TI  - Diastolic dysfunction and mortality in diabetic patients on hemodialysis: a 4.25
      year controlled prospective study.
AB  - Among patients on hemodialysis, the mortality rate is higher in individuals with
      diabetes than in nondiabetic individuals, especially due to cardiovascular
      causes. The objective of the present study was to evaluate the role of
      echocardiographic abnormalities to predict mortality in diabetic patients
      starting hemodialysis. A 4.25-year prospective study was carried out with 40
      diabetic and 28 nondiabetic patients starting hemodialysis in five dialysis
      centers in the metropolitan area of Porto Alegre, Brazil, between August 1996 and
      June 1999. Cardiovascular status was evaluated based on World Health Organization
      criteria, resting electrocardiogram (ECG), myocardial scintigraphy (at rest and
      after dipyridamole administration), and M-mode and Doppler echocardiography. Left
      ventricular diastolic function was classified into the following filling
      patterns: normal, impaired relaxation, pseudonormal, or restrictive. The survival
      rate was analyzed by Kaplan-Meier curves and predictors of death by Cox's
      proportional-hazards model. At the end of the study, the overall mortality rate
      was higher in patients with diabetes [19/40 (47.5%)] than in those without
      diabetes [2/28 (7.1%), P=.0013, log rank test]. Pseudonormal and restrictive
      filling patterns (HR: 3.2; 95% CI: 1.2-8.8; P=.02) and presence of diabetes (HR:
      4.7; 95% CI: 1.03-21.4; P=.04) were associated with mortality. In conclusion,
      left ventricular diastolic dysfunction (LVDD) was the main predictor of mortality
      in this cohort of diabetic and nondiabetic patients starting dialysis. Intensive
      treatment of cardiovascular risk factors before the start of dialysis and during
      the treatment might reduce the mortality rate in diabetic patients.

PMID- 15993354
TI  - Health-related quality of life in the VA Feasibility Study on glycemic control
      and complications in type 2 diabetes mellitus.
AB  - OBJECTIVE: The Veterans Affairs Cooperative Study in Diabetes Mellitus Type 2
      Feasibility Trial (VA CSDM) studied standard and intensive glycemic treatment
      groups, achieving and maintaining for 27 months a difference in HbA1c of 2.1%
      (9.2% vs. 7.1%, respectively). A substudy planned in advance examined health
      status as assessed by a health status questionnaire obtained at baseline and 24
      months. DESIGN AND METHODS: A randomized, prospective trial was carried out at
      five VA Medical Centers from 1990 to 1993. The sample involved 153 male veterans
      40-69 years of age and with diabetes duration of 8+/-4 years, who were
      suboptimally controlled with standard glucose lowering treatment. The
      participants were randomized to intensive and standard treatment groups. In
      addition to a variety of indicators of glycemic control and complications, health
      related qualify of life data were assessed using a 20-question version of the
      Medical Outcome Study instrument. Scores were evaluated at baseline and 24 months
      for changes between the treatment groups. RESULTS: The two groups were similar at
      baseline with respect to age, duration of diabetes, complications, comorbidities,
      and reported physical activity. The intensive treatment group had more frequent,
      mandatory self-glucose monitoring (vs. occasional measurement in the standard)
      and received two or more daily insulin injections (only one in the standard).
      This group had three times the number of clinic visits and 10-fold higher
      reported incidence of mild/moderate hypoglycemia. There were no significant
      changes in the health status over time in either the standard or intensive
      treatment groups, nor was there a difference between the two groups. CONCLUSIONS:
      Intensive glucose control in advanced Type 2 diabetes mellitus (DM) has no effect
      on health status over 2 years. The successful lowering of glycemia does not
      improve health-related quality of life nor do the increased demands of an
      intensive therapy regimen worsen it.

PMID- 15993355
TI  - Changing associations between progressive cardiovascular autonomic neuropathy and
      carotid atherosclerosis with increasing duration of type 2 diabetes mellitus.
AB  - To clarify associations between cardiovascular autonomic neuropathy (CAN) and the
      progression of carotid artery atherosclerosis in Type 2 diabetic patients,
      cardiovascular autonomic nerve function was related to carotid artery ultrasound
      in 61 Type 2 diabetic patients, 5 and 8 years after the diagnosis of diabetes.
      Between 5 and 8 years after diagnosis, age-adjusted acceleration index (AI)
      decreased (from -0.306+/-1.034 to -0.702+/-1.072; P=.0139), whereas age-adjusted
      expiration/inspiration (E/I) ratio was unchanged (-0.583+/-1.038 and -0.828+/
      1.028; P=.1164). Intima-media thickness (IMT) increased in both the common
      carotid artery (CCA; from 0.854+/-0.219 to 0.913+/-0.241 mm; P<.0001) and the
      carotid bulb (from 1.789+/-0.714 to 2.128+/-0.881 mm; P<.0001), corresponding to
      a yearly IMT increase of 0.032+/-0.039 mm in the CCA and 0.146+/-0.204 mm in the
      carotid bulb. This value did not correlate with the AI or E/I ratios. In age
      controlled partial correlation in the first examination, AI correlated inversely
      with mean (r=-.33, P=.018) IMT in the CCA, but not with IMT in the carotid bulb
      (r=-.14, P=.303). However, in contrast to the first examination, at follow-up, AI
      correlated inversely with the mean IMT of the carotid bulb (r=-.40, P=.007),
      lumen diameter of the CCA (r=-.31, P=.034), and plaque score (r=-.29, P=.041),
      but not with IMT of the CCA (r=-.04, P=.861). There were no correlations between
      the E/I ratio and carotid variables. In conclusion, CAN was associated with
      features of carotid atherosclerosis, which, in the carotid bulb, might affect
      baroreceptor function with the progression of Type 2 diabetes.

PMID- 15993356
TI  - A comparison of the Glycosylation Gap and Hemoglobin Glycation Index in patients
      with diabetes.
AB  - PROBLEM: The Glycosylation Gap (GGAP) based on fructosamine (F) measurement and
      the Hemoglobin Glycation Index (HGI) based on mean blood glucose (MBG) are two
      indices of between-individual differences in glycated hemoglobin (HbA1c) adjusted
      for glycemia. We sought to simultaneously compare GGAP with HGI and other
      estimates of glycemia. METHODS: HbA1c, F, and MBG level were obtained at a clinic
      visit from 62 patients with Type 1 diabetes. GGAP and HGI were calculated from
      the data as previously described. The variables were compared by correlation
      analysis. The concordance of patient classification by GGAP and HGI was compared
      by weighted kappa test. RESULTS: The mean HbA1c=11.1+/-2.7%, F=372.0+/-136.6
      mol/l, MBG=186.5+/-58.4 mg/dl, HGI=0.0+/-2.0, and GGAP=0.0+/-1.9. MBG, HbA1c, and
      F were all highly correlated with each other. The HGI and GGAP were highly
      correlated (r=.73, P<.0001) and similar in both magnitude and direction. There
      was good agreement between HGI and GGAP classifications of patients into high,
      moderate, and low glycation groups (P<.0075). CONCLUSIONS: GGAP and MBG give
      similar information regarding between-patient differences in HbA1c among patients
      with diabetes. Thus, biological variation in HbA1c is not an artifact of
      variability in glucose measurements comprising the MBG. Individual patient
      factors influence the intracellular glycation of HbA1c in addition to the effect
      of extracellular glycemia, which is manifested as a between-individual biological
      variation in HbA1c.

PMID- 15993357
TI  - Identification of urinary protein pattern in type 1 diabetic adolescents with
      early diabetic nephropathy by a novel combined proteome analysis.
AB  - Diabetic nephropathy is the main cause of morbidity and mortality in patients
      with Type 1 diabetes mellitus. Microalbuminuria has been established as a risk
      factor for the development and the progression of diabetic renal disease. A
      strong demand exists for better technologies to provide accurate diabetic
      nephropathy risk estimates before renal functional or structural disturbances
      already become established. Here, we present the application of a novel
      proteomics technology identifying urinary polypeptides and proteins. In this
      pilot study, we investigated 44 Type 1 diabetic patients with more than 5 years
      of diabetes duration compared with an age-matched control group. Random spot
      urine samples were examined utilizing high-resolution capillary electrophoresis
      (CE), coupled to mass spectrometry (MS). More than 1000 different polypeptides,
      characterized by their separation time and mass, were found between 800 Da and
      66.5 kDa. Mathematical analysis revealed specific clusters of 54 polypeptides
      only found in Type 1 diabetic patients and an additional 88 polypeptides present
      or absent in patients with beginning nephropathy defined by the albumin-to
      creatinine ratio (ACR; >35 mg/mmol). We observed polypeptide patterns
      characteristic for healthy controls and diabetic patients and subdivision of
      patients according to the excretion of polypeptides typical for diabetic
      nephropathy. Our study revealed that the urinary proteome contains a much greater
      variety of polypeptides than previously recognized and demonstrated the
      successful application of a novel high-throughput technology towards the human
      urinary proteome. Future prospective studies with the application of this
      technique may enable the earlier and more accurate detection of individuals at
      high risk to develop diabetic nephropathy.

PMID- 15993358
TI  - Retinal vascular integrity following correction of diabetic ketoacidosis in
      children and adolescents.
AB  - OBJECTIVE: Increased permeability of the cerebral microvasculature occurs during
      the treatment of diabetic ketoacidosis (DKA). Microvascular changes consistent
      with diabetic retinopathy have been reported prior to and after the treatment of
      DKA. This study evaluated the structural and functional aspects of the retina
      immediately following the correction of DKA. METHODS: Seven young patients had
      comprehensive ophthalmologic examinations, including fluorescein angiography,
      within 24 h after the correction of severe DKA (pH <7.2). RESULTS: None of the
      patients had clinical, photographic, or angiographic evidence of a retinal
      abnormality. CONCLUSION: The blood-retinal barrier (BRB) does not experience the
      same degree of perturbation as the blood-brain barrier (BBB) does and may be a
      protected site during the insult of DKA and its treatment. The greater stability
      of the retinal microvasculature may be due to the increased number of pericytes
      in the BRB in comparison with the BBB.

PMID- 15993359
TI  - Clinical evidence for the safety of GAD65 immunomodulation in adult-onset
      autoimmune diabetes.
AB  - The purpose of this Phase II study was to evaluate if alum-formulated human
      recombinant GAD65 is safe and does not compromise beta cell function. The study
      was conducted as a randomized, double blind, placebo-controlled, dose-escalation
      clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA)
      patients who received either placebo or 4, 20, 100, or 500 microg Diamyd
      subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta
      cell function tests, diabetes status assessment, hematology, biochemistry, and
      cellular and humoral immunological markers, were repeatedly assessed over 24
      weeks. None of the patients had significant study-related adverse events (AE).
      Fasting c-peptide levels at 24 weeks were increased compared with placebo
      (P=.0015) in the 20 microg but not in the other dose groups. In addition, both
      fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from
      baseline to 24 weeks in the 20 microg dose group. GADA log levels clearly
      increased (P=.0002) in response to 500 microg Diamyd. The
      (CD4+)(CD25+)/(CD4+)(CD25-) cell ratio increased (P=.0128) at 24 weeks in the 20
      microg group. No sudden increase in HbA1c or plasma glucose or decrease in beta
      cell function was observed in any of the dose groups. These positive findings for
      clinical safety further support the clinical development of Diamyd as a
      therapeutic to prevent autoimmune diabetes.

PMID- 15993360
TI  - Bone morphogenetic protein signaling in joint homeostasis and disease.
AB  - Despite advances in therapies that target inflammation and tissue destruction in
      chronic arthritis, stimulation of tissue repair and restoration of joint
      function, the ultimate goal of treatment, is far from achieved. We introduce a
      new paradigm that may help to improve our understanding and management of chronic
      arthritis. The presence or absence of tissue responses distinguishes destructive
      arthritis, steady-state arthritis and remodeling arthritis. Increasing evidence
      suggests that reactivation of embryonic molecular pathways is an important
      mechanism to stimulate postnatal tissue repair. Bone Morphogenetic Proteins
      (BMPs) have critical roles in skeletal development and joint morphogenesis, but
      also in postnatal joint homeostasis and joint tissue remodeling. Therefore,
      modulation of BMP signaling may be an attractive therapeutic target in chronic
      arthritis to restore homeostasis and function of synovial joints.

PMID- 15993361
TI  - Shifting paradigms: gradient structure in morphology.
AB  - Morphology is the study of the internal structure of words. A vigorous ongoing
      debate surrounds the question of how such internal structure is best accounted
      for: by means of lexical entries and deterministic symbolic rules, or by means of
      probabilistic subsymbolic networks implicitly encoding structural similarities in
      connection weights. In this review, we separate the question of subsymbolic
      versus symbolic implementation from the question of deterministic versus
      probabilistic structure. We outline a growing body of evidence, mostly external
      to the above debate, indicating that morphological structure is indeed
      intrinsically graded. By allowing probability into the grammar, progress can be
      made towards solving some long-standing puzzles in morphological theory.

PMID- 15993362
TI  - Presence of INFgamma-secreting lymphocytes specific to prostate antigens in a
      group of chronic prostatitis patients.
AB  - Acute and chronic infectious prostatitis are the best understood of the prostate
      syndromes, but they are the least frequent. In contrast, although chronic non
      infectious prostatitis is the most frequent syndrome, its cause has proved
      elusive despite years of investigation. In the present study, we analyzed a group
      of patients with infectious and non-infectious chronic prostatitis in order to
      search for the presence of a possible autoimmune response to prostate antigens.
      We demonstrated the presence of lymphocytes able to proliferate in response to
      known human prostate antigens such as PSA and PAP only in a group of patients
      with non-infectious chronic prostatitis. We observed that, as in other autoimmune
      diseases, a proliferative response against two or more autoantigens was a common
      feature. Moreover, when INFgamma and IL-10 levels were measured in culture
      supernatants, significantly elevated levels of INFgamma were detected only in
      samples from patients with positive proliferative response to prostate antigens.
      Interestingly, only these patients showed significantly elevated levels of
      inflammatory cytokines (IL-1 and TNF-alpha) in seminal plasma, arguing for a
      local inflammation of non-infectious cause. Our results show that INFgamma
      secreting lymphocytes specific to prostate antigens are in fact detected in 34%
      of the patients with chronic non-infectious prostatitis. We speculate that these
      cells could be involved in the inflammatory process taking place in the prostate
      gland and therefore could alter its biological function.

PMID- 15993363
TI  - Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and
      their role in multiple organ dysfunction.
AB  - To evaluate the role of activated cytotoxic cells in patients with severe sepsis
      (n = 32) or septic shock (n = 8), direct (granzymes A and B) as well as indirect
      markers (cytokines) for cytotoxic cell activation were measured. Elevated IL
      12p40 levels had been detected in 58% of the sepsis patients, whereas only a few
      had detectable TNF-alpha, IFN-gamma, or IL-12p70 levels. Granzymes A and B levels
      were elevated in 42.5% and 22.5%, respectively. IL-12p40 inversely correlated
      with disease severity. Inflammatory parameters (IL-6) and coagulation markers
      were significantly lower and higher, respectively, in patients with elevated IL
      12p40 and granzyme B levels, as compared to those with normal levels. Elevation
      of granzyme A directly correlated with the increase of apoptotic markers.
      Activated cytotoxic cells reflected by elevated granzymes A and/or B were found
      in 50% of our sepsis patients. This group showed a higher mortality and a worse
      organ function.

PMID- 15993364
TI  - Lipopolysaccharide binding protein-deficient mice have a normal defense against
      pulmonary mycobacterial infection.
AB  - Lipopolysaccharide (LPS) binding protein (LBP) facilitates the transfer of LPS of
      Gram-negative bacteria to the pattern recognition receptor CD14, resulting in
      activation of immunocompetent cells. LBP can also facilitate the binding of
      lipoarabinomannan, a major cell wall component of mycobacteria, to immune cells.
      To determine the role of LBP in the immune response to pulmonary Mycobacterium
      tuberculosis infection, LBP gene-deficient (-/-) and normal wild-type (WT) mice
      were intranasally infected with M. tuberculosis. LBP-/- mice displayed a similar
      survival and mycobacterial outgrowth in lungs and liver, although they
      demonstrated a reduced lymphocyte recruitment and activation during the early
      stages of infection. The clearance of pulmonary infection with the non-pathogenic
      M. smegmatis was also unaltered in LBP-/- mice. These data suggest that LBP does
      not contribute to an effective host response in M. tuberculosis infection.

PMID- 15993365
TI  - Identification of prolactin as a novel immunomodulator on the expression of co
      stimulatory molecules and cytokine secretions on T and B human lymphocytes.
AB  - We investigate the immunomodulator role of prolactin (PRL) on CD4+ and B cell
      activation from healthy subjects in comparison with hyperprolactinemic patients.
      Peripheral blood mononuclear cells, CD4+ or B cells, purified, were cultured
      under different conditions, as follows: with mitogen, without stimulus, with
      different concentrations of human PRL, with unspecific mitogen plus PRL, or with
      antibodies against PRL. The results revealed that PRL is produced by lymphocytes,
      the expression of CD69 and CD154 molecules, and interleukin secretions depend
      partially on the autocrine PRL, this is supported by the findings that secretions
      of IL-2, IFNgamma, and co-stimulatory molecule expression were markedly reduced
      when autocrine PRL was blocked with anti-PRL antibodies. Furthermore, PRL
      activity was only observed during the first 2 h after activation. In contrast, B
      cell culture did not show any alteration by adding or blocking PRL in the
      expression of CD40 and CD86 in both groups: healthy subject and
      hyperprolactinemic patients.

PMID- 15993366
TI  - Lymphocyte subsets' reference ranges in an age- and gender-balanced population of
      100 healthy adults--a monocentric German study.
AB  - Region-specific reference ranges for adult peripheral blood lymphocyte subsets
      have been established in few countries around the world, but most studies were
      restricted to younger adults for monitoring of HIV patients. The aim of this
      investigation was to establish age- and gender-specific reference ranges for
      healthy adults. Lymphocyte subsets were examined in 100 healthy volunteers (50
      males, 50 females) aged 19-85 years by two-color flow cytometric analysis with a
      FACSCalibur. A statistically significant decline in the mean numbers of CD3+/CD8+
      T cells and CD19+ B cells was observed beyond an age of 50 years, whereas the
      mean counts of NK cells and CD4+/CD8+ ratio significantly increased beyond the
      age of 50. Females < or = 50 years had significantly higher mean CD4+ T cell
      counts and lower NK cell counts than males < or = 50 years. Based on these
      results, we established reference values for three subgroups: males < or = 50
      years, females < or = 50 years, and males/females > 50 years.

PMID- 15993367
TI  - Construction of a set Gateway-based destination vectors for high-throughput
      cloning and expression screening in Escherichia coli.
AB  - We describe here the construction of a 10-Gateway-based vector set applicable for
      high-throughput cloning and for expressing recombinant proteins in Escherichia
      coli. Plasmids bear elements required to produce recombinant proteins under
      control of the T7 promoter and encode different N-terminal partners. Since the
      vector set is derived from a unique backbone, a consistent comparison of the
      impact of fusion partner(s) on protein expression and solubility is easily
      amenable. Finally, a sequence encoding a six-histidine tag has been inserted to
      be in frame with the cloned open reading frame either at its C terminus or at the
      N terminus, giving the flexibility of choosing the six-histidine tag location for
      further purification. To test the applicability of our vector set, expression and
      solubility profile and six-histidine tag accessibility have been demonstrated for
      two Bacillus subtilis signaling proteins' encoding genes (SBGP codes E0508 and
      E0511).

PMID- 15993368
TI  - A surface modification strategy on silicon nitride for developing biosensors.
AB  - A surface modification strategy for the use of giant magnetoresistive materials
      in the detection of protein-protein interactions is developed. This modification
      strategy is based on silanization of semiconductive materials. A native silicon
      nitride surface was treated with concentrated hydrofluoric acid to improve
      surface homogeneity. Nano-strip was used to oxidize silicon nitride to form a
      hydrophilic layer. Aminopropyltriethoxysilane was subsequently used to
      functionalize the treated surfaces to form amine groups, which were further
      activated with glutaraldehyde to introduce a layer of aldehyde groups. The
      effectiveness of this modification strategy was validated by chemiluminescence
      immunoassays of purified 6x His-HrpW of Pseudomonas syringae pv. tomato DC3000
      and human transferrin. Signals with intensities related to concentrations of
      these two immobilized model proteins were observed. The modified surface was also
      validated by a more complex system: intercellular proteins secreted by DC3000.
      HrpW in these protein mixtures was successfully recognized by anti-HrpW
      antibodies when mixed proteins were immobilized onto activated surfaces. This
      surface modification strategy provides a platform onto which proteins can be
      directly immobilized for biosensor and protein array applications.

PMID- 15993369
TI  - Sexual dimorphism in urinary metabolite profiles of Han Wistar rats revealed by
      nuclear-magnetic-resonance-based metabonomics.
AB  - Gender-dependent metabolic variation in Han Wistar rats (n=25 male and n=25
      female) was investigated using (1)H nuclear magnetic resonance (NMR) spectroscopy
      of urine coupled with chemometric methods. Statistically discriminatory regions
      of the spectra for male and female rats were identified and biomarker
      characterization was achieved by the further application of solid-phase
      extraction chromatography with NMR detection and high-performance liquid
      chromatography mass spectrometry. A novel discriminating molecule was identified
      as the sulfate conjugate of m-hydroxyphenylpropionic acid, which was excreted in
      higher concentrations by male rats. Other gender-related metabolite differences
      in the urine profiles included higher levels of trimethylamine-N-oxide, N,N'
      dimethylglycine, m-hydroxyphenylpropionic acid, N-acetylglycoprotein, and cholate
      in samples from female animals. These studies emphasize the utility of
      multicomponent metabolic profiling for investigating physiological and genetic
      variation in experimental animals that may be of relevance to their use as models
      of toxicity and disease.

PMID- 15993370
TI  - Special methods for the analysis of ether lipid structure and metabolism in
      archaea.

PMID- 15993371
TI  - Protein sample concentration by repeated loading onto SDS-PAGE.

PMID- 15993372
TI  - A procedure for measuring triacylglyceride and cholesterol content using a small
      amount of tissue.
AB  - This paper describes the development of a procedure for measuring total lipid,
      triacylglyceride, and cholesterol content using small amounts of tissue (50 mg
      for liver samples and 10 mg for adipose tissue samples). In the first step, total
      lipids are extracted with an organic solvent mixture of hexane and isopropanol.
      In the second step, extracted lipids are emulsified by sonication in a buffer
      containing 1,4-piperazinediethanesulfonic acid (28.75 mM), magnesium
      chloride.6H(2)O (57.76 mM), free fatty acids-bovine serum albumin (8.76 microM),
      and sodium dodecyl sulfate (0.1%). Lipid concentrations from the resulting
      emulsion can then be assessed using commercial enzymatic kits. This method is
      also suitable for determining direct homogenate triacylglyceride and total
      cholesterol content in cases where a lipid percentage is not needed. The proposed
      method increases the yield of lipid recovery from small tissue samples and allows
      the measurement of both triacylglyceride and cholesterol content from a single
      starting sample. The methodology described here is the first to accomplish
      simultaneous determination of both parameters and is potentially useful for
      animal small tissue samples, particularly human biopsy samples.

PMID- 15993373
TI  - Amperometric biosensor for determining human salivary phosphate.
AB  - An amperometric biosensor was constructed for analysis of human salivary
      phosphate without sample pretreatment. The biosensor was constructed by
      immobilizing pyruvate oxidase (PyOD) on a screen-printed electrode. The presence
      of phosphate in the sample causes the enzymatic generation of hydrogen peroxide
      (H(2)O(2)), which was monitored by a potentiostat and was in proportion to the
      concentration of human salivary phosphate. The sensor shows response within 2s
      after the addition of standard solution or sample and has a short recovery time
      (2 min). The time required for one measurement using this phosphate biosensor was
      4 min, which was faster than the time required using a commercial phosphate
      testing kit (10 min). The sensor has a linear range from 7.5 to 625 microM
      phosphate with a detection limit of 3.6 microM. A total of 50 salivary samples
      were collected for the determination of phosphate. A good level of agreement
      (R(2)=0.9646) was found between a commercial phosphate testing kit and the
      phosphate sensor. This sensor maintained a high working stability (>85%) after
      12h operation and required only a simple operation procedure. The amperometric
      biosensor using PyOD is a simple and accurate tool for rapid determinations of
      human salivary phosphate, and it explores the application of biosensors in oral
      and dental research and diagnosis.

PMID- 15993374
TI  - [Impact of laparoscopy on the management of adrenal diseases. A retrospective
      study of 220 patients].
AB  - OBJECTIVE: Soon after its introduction in 1992, laparoscopic adrenalectomy became
      the gold standard in the surgical management of most adrenal tumors. The aim of
      this study was to assess the influence of laparoscopy on surgical indications.
      PATIENTS AND METHODS: Between 1994 and 2003, 220 adrenalectomies were performed,
      179 among them by a laparoscopic approach. There were 137 females and 83 males.
      The mean age was 53 years (range 15-83 years). RESULTS: The indications of
      adrenalectomy were: Cushing syndrome 18%, pheochromocytoma 31%, Conn syndrome
      16%, incidentaloma 21%, and malignant tumours 13%. Laparoscopic approach was
      performed in 81% of the cases and the conversion rate was 11%. There were 3
      postoperative deaths (2 after laparoscopy). The mean hospital stay was 7.6 days
      in the laparoscopic group, and 13.6 days in the open surgery group. CONCLUSIONS:
      This study is consistent with the findings of the literature supporting that
      there are no indications for the open procedure in case of small benign lesions.
      The video-asisted adrenalectomy had not changed the management of the adrenal
      incidentaloma. Today, the laparoscopic approach seems to be adapted also for
      malignant disease.

PMID- 15993375
TI  - Safety implications of cultural and cognitive issues in nuclear power plant
      operation.
AB  - This research project was designed to investigate cultural and cognitive issues
      related to the work of nuclear power plant operators during their time on the job
      in the control room and during simulator training (emergency situations), in
      order to show how these issues impact on plant safety. The modeling of the
      operators work deals with the use of operational procedures, the constant changes
      in the focus of attention and the dynamics of the conflicting activities. The
      paper focuses on the relationships between the courses of action of the different
      operators and the constraints imposed by their working environment. It shows that
      the safety implications of the control room operators' cognitive and cultural
      issues go far beyond the formal organizational constructs usually implied. Our
      findings indicate that the competence required for the operators are concerned
      with developing the possibility of constructing situation awareness, managing
      conflicts, gaps and time problems created by ongoing task procedures, and dealing
      with distractions, developing skills for collaborative work.

PMID- 15993376
TI  - Negotiating participation: understanding the "how" in an ergonomic change team.
AB  - In participatory ergonomic (PE) interventions, "how" effective participation by
      workplace parties can be achieved remains unclear. We conducted a case study of
      the dynamics of an ergonomic change team (ECT) process in a medium-sized (175
      employees) automotive foam manufacturing plant. We present analyses of observer
      field notes and post-intervention interviews from which key elements on the
      dynamics of the "how" emerged: (1) impacts of facilitators' involvement and
      interests; (2) tensions in delimiting the scope of ECT activities; issues around
      (3) managing meetings and (4) realizing labour and management participation; and
      (5) workplace ECT members' difficulties in juggling other job commitments and
      facing production pressures. We highlight the ongoing negotiated nature of
      responses to these challenges by labour, management and ergonomic facilitator
      members of the ECT. We argue for greater examination of the social dynamics of PE
      processes to identify additional ways of fostering participation in ergonomic
      project implementation.

PMID- 15993377
TI  - Transcytosis of calcium from bone by osteoclast-like cells evidenced by direct
      visualization of calcium in cells.
AB  - 'Transcytosis' of calcium (Ca) from bone by osteoclasts was identified by using a
      newly developed method that uses fixed or living osteoclast-like cells previously
      differentiated in vitro, a Ca-specific cell-membrane-impermeable fluorescent dye,
      and confocal laser scanning microscopy. This method, called the cell-membrane
      impermeable dye method, revealed that in fixed osteoclast-like cells, a large
      quantity of Ca was confined within vacuoles and transported toward the apical
      cell membrane in the cells. These Ca-confined vacuoles were co-localized with
      marker proteins of both ruffled border and lysosome. The vacuoles were disrupted
      when treated with an inhibitor of ruffled border ATPase. In living osteoclast
      like cells, Ca-confined vacuoles were again preferentially located at the central
      region and near the apical cell membrane. These results suggest actual
      transcytosis of Ca from bone by osteoclasts, and are the first direct evidence of
      the significant role of osteoclasts in the entire process of Ca metabolism in
      bone.

PMID- 15993379
TI  - Cyclic endoperoxides of beta-carotene, potential pro-oxidants, as products of
      chemical quenching of singlet oxygen.
AB  - Photoprotection by carotenoids is generally considered to be based on the
      photophysical quenching of triplets and singlet oxygen. There is also
      accumulating evidence of an alternative, chemical quenching of triplets and
      singlet oxygen by carotenoids. We report the identification of relatively stable
      cyclic mono- and diendoperoxides as first products of such an alternative
      reaction. Nevertheless, these species remain reactive and in the dark cause
      autooxidation of beta-carotene in our model system. Their formation could explain
      the intriguing pro-oxidant and cytotoxic activity of carotenoids.

PMID- 15993378
TI  - Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or
      caspase-inhibitory functions.
AB  - CrmA is a cowpox virus serpin required for full host infectivity and virulence.
      Residues 51-56 (DKNKDD), the only region that differs significantly from related
      viral serpins, were investigated for functional importance. A 1.6A X-ray
      structure reported here showed that this region can adopt either structured or
      unstructured conformations. Three variants were expressed, one with the region 51
      56 deleted, one substituted by alanines, and one in which this region was
      replaced by the sequence encoded in smallpox virus. NMR showed that the region is
      an exposed, flexible loop that can be deleted without perturbing the serpin. The
      region is also very susceptible to proteolysis. Significantly, inhibition of
      caspases 1 and 8 was unaffected by the mutations, and each of the variants was as
      effective as wild-type CrmA in promoting survival from apoptosis induced by tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL). Thus, although the 51
      56 region of CrmA is unique, and is exposed and highly susceptible to
      proteolysis, any in vivo role must involve a function other than proteinase
      inhibition or cell sparing.

PMID- 15993380
TI  - Coenzyme Q distribution in HL-60 human cells depends on the endomembrane system.
AB  - Coenzyme Q (Q) is an essential factor in the mitochondrial electron chain but
      also exerts important antioxidant functions in the rest of cell membranes of
      aerobic organisms. However, the mechanisms of distribution of Q among cell
      membranes are largely unclear. The aim of the present work is to study the
      mechanisms of distribution of endogenous Q(10) and exogenous Q(9) among cell
      membranes in human HL-60 cells. Endogenous Q(10) synthesized using the
      radiolabelled precursor [(14)C]-pHB was first detected in mitochondria, and it
      was later incorporated into mitochondria-associated membranes and endoplasmic
      reticulum (ER). Plasma membrane was the last location to incorporate [(14)C]
      Q(10). Brefeldin A prevented Q(10) incorporation in plasma membrane. Exogenous
      Q(9) was preferably accumulated into the endo-lysosomal fraction but a
      significant amount was distributed among other cell membranes also depending on
      the brefeldin-A-sensitive endomembrane system. Our results indicate that
      mitochondria are the first location for new synthesized Q. Exogenous Q is mainly
      incorporated into an endo-lysosomal fraction, which is then rapidly incorporated
      to cell membranes mainly to MAM and mitochondria. We also demonstrate that both
      endogenous and dietary Q is distributed among endomembranes and plasma membrane
      by the brefeldin A-sensitive endo-exocytic pathway.

PMID- 15993381
TI  - Comparison of two self-report instruments for assessing binge eating in bariatric
      surgery candidates.
AB  - This study compared two self-report methods for assessing binge eating in
      severely obese bariatric surgery candidates. Participants were 249 gastric bypass
      candidates who completed the Questionnaire on Eating and Weight Patterns-Revised
      (QEWP-R) and the Eating Disorder Examination-Questionnaire (EDE-Q) prior to
      surgery. Participants were classified by binge eating status (i.e., no or
      recurrent binge eating) with each of the measures. The degree of agreement was
      examined, as well as the relationship between binge eating and measures of
      convergent validity. The two measures identified a similar number of patients
      with recurrent binge eating (i.e., at least 1 binge/week); however, overlap was
      modest (kappa=.26). Agreement on twice weekly binge eating was poor (kappa=.05).
      The QEWP-R and EDE-Q both identified clinically meaningful groups of binge
      eaters. The EDE-Q appeared to differentiate between non/infrequent bingers and
      recurrent bingers better than the QEWP-R, based on measures of convergent
      validity. In addition, the EDE-Q demonstrated an advantage because it identified
      binge eaters with elevated weight and shape overconcern. Using the self-report
      measures concurrently did not improve identification of binge eating in this
      study. More work is needed to determine the construct validity and clinical
      utility of these measures with gastric bypass patients.

PMID- 15993382
TI  - Erythropoietin attenuated high glucose-induced apoptosis in cultured human aortic
      endothelial cells.
AB  - High glucose-induced apoptosis in vascular endothelial cells may contribute to
      the acceleration of atherosclerosis associated with diabetes. Here, we show that
      erythropoietin attenuates high glucose-induced apoptosis in cultured human aortic
      endothelial cells (HAECs). Exposure of HAECs to high glucose level for 72h
      significantly increased the number of apoptotic cells compared with normal
      glucose level, as evaluated by TUNEL assay. Simultaneous addition of
      erythropoietin (100 U/ml) significantly attenuated high glucose-induced
      apoptosis. In parallel, exposure to high glucose level induced caspase-3
      activation and erythropoietin also prevented it. Erythropoietin stimulated Akt
      phosphorylation in a dose-dependent manner (1-100 U/ml). PI3 kinase inhibitor,
      wortmannin or LY294002 eliminated erythropoietin's inhibitory effect on caspase-3
      activity. In conclusion, erythropoietin may attenuate high glucose-induced
      endothelial cell apoptosis via PI-3 kinase pathway. Replacing therapy with
      erythropoietin is often used for correction of renal anemia, but may have
      potential in preventing atherosclerosis in diabetic patients with end-stage renal
      failure.

PMID- 15993383
TI  - PPARgamma agonists diminish serum VEGF elevation in diet-induced insulin
      resistant SD rats and ZDF rats.
AB  - We investigated the effect of peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists on serum vascular endothelial growth factor (VEGF) in diet
      induced insulin resistant SD rats and ZDF rats. SD rats fed a high fat/sucrose
      diet showed increases in serum insulin and VEGF (both p < 0.01). Treatment with a
      PPARgamma agonist GI262570 normalized the diet-elevated insulin and VEGF (both p
      < 0.01). There was a positive correlation between serum insulin and VEGF (p <
      0.05) in SD rats. ZDF rats had higher serum glucose, insulin, and VEGF than
      Zucker lean rats (all p < 0.01). Treatment of ZDF rats with PPARgamma agonist
      pioglitazone decreased serum glucose and VEGF (both p <0.01). There was a
      positive correlation between glucose and VEGF in ZDF rats (p < 0.05). In 3T3-L1
      adipocytes, GI262570 did not affect insulin-stimulated VEGF secretion. These
      studies demonstrated that hyperinsulinemia in SD rats and hyperglycemia in ZDF
      rats were associated with increased serum VEGF; PPARgamma agonists normalized
      serum insulin, glucose, and VEGF, but did not affect VEGF secretion in vitro.

PMID- 15993384
TI  - Identification of a novel gene, HCR2, in aorta of hypercoagulable rats using
      suppression subtractive hybridization.
AB  - Screening and identification of novel genes involved in hypercoagulable state
      (HCS) is important in understanding the underlying mechanisms of development of
      atheroslerosis, which implicated in critical vascular diseases such as coronary
      heart disease and stroke. HCS was induced in rats with high carbohydrate diet.
      Subtractive hybridization experiments between aorta tissues from hypercoagulable
      rats and controls showed that a novel cDNA (GenBank Accession No. AY234417),
      designated as hypercoagulability related gene-2 (HCR2), was highly expressed in
      aorta tissue. The predicted protein encoded by HCR2 contains 78 amino acids,
      which has a theoretical isoelectric point (pI) of 8.59 and molecular weight (MW)
      of 8841.7 based on sequence analysis. Our data suggest that HCR2 may be involved
      in HCS and identification of the gene may contribute to our understanding of the
      mechanisms for the production of a hypercoagulable state of several critical
      clinical disorders.

PMID- 15993385
TI  - Effects of centrally administered vasopressin on orofacial pain perception in
      rats.
AB  - Vasopressin (AVP) appears in the cerebrospinal fluid and plays an important role
      in nociceptive modulation in the central nervous system. The effect of increased
      concentration of AVP in the cerebrospinal fluid on the excitability of the
      hypoglossal nerve nucleus was investigated. The experiments were carried out on
      rats under chloralose anesthesia. Amplitudes of the retractory evoked tongue
      jerks (ETJ) of the outstretched tongue during the perfusion of cerebral
      ventricles with solutions containing AVP or its antagonists and also opioid and
      serotonin antagonists were recorded. Perfusion of the ventricles with AVP in 100
      microM concentration suppressed the ETJ amplitude to 66 +/- 3.83%, and in 200
      microM concentration, to 53 +/- 3.18% of the control. V1 vasopressin receptor
      antagonist, d(CH2)5,Tyr(Me)AVP, blocked the suppressive effect caused by cerebral
      ventricle perfusion with AVP from 64 +/- 4.11% to 83 +/- 1.58%, whereas V2
      vasopressin receptor antagonist, d(CH2)5[Ile2, Ile4]AVP, did not block the
      antinociceptive effect of AVP. Analgesic effect of AVP was also inhibited by
      opioid and serotonin receptor antagonists, naloxone and methysergide,
      respectively. Naloxone blocked the suppressive effect of 100 microM AVP from 64
      +/- 5.63% to 92 +/- 3.70% and methysergide from 65 +/- 3.62% to 80 +/- 2.72% of
      the control. The results indicate that exogenous AVP plays an antinociceptive
      role in the brain of rats penetrating the lining of the cerebral ventricles into
      the cerebrospinal fluid and exerting a modulating effect on the tongue motor
      center situated near III and IV cerebral ventricle. V1 vasopressin receptor, but
      not V2 vasopressin receptor, is involved in this activity in the CNS. The
      antinociception of AVP seems to be mediated by opioid and serotonergic pathways.

PMID- 15993386
TI  - Co-expression of radial glial marker in macrophages/microglia in rat spinal cord
      contusion injury model.
AB  - Macrophages/microglia are implicated in spinal cord injury but their precise role
      in the process is not clear. Our previous studies have reported that radial glia
      (RG) possess properties of neural stem cells and remerged after central nervous
      system (CNS) injury which may play an important role in neural repair and
      regeneration. In the present study, we examined the expression of ED1 (a specific
      marker for activated macrophages/microglia) and RG in a spinal cord injury (SCI)
      model and detected the activation at 1, 4, 8, and 12 weeks in both dorsal
      funiculus and ventral white matter after SCI. For both ED1-positive cells and RG
      cells, there was a gradual increase in density and in number from 1 to 4 weeks
      followed by down-regulation up to 12 weeks after injury. The morphologies of
      macrophages and radial glia were different. However, some ED1-positive cells were
      also stained by RG marker. These results suggest that macrophages may have some
      lineage to radial glial cells.

PMID- 15993387
TI  - Altered nitric oxide synthase and PKC activities in cerebellum of gamma
      irradiated neonatal rats.
AB  - In this study, we show that one single dose of gamma-irradiation at birth induces
      an inhibition of the cerebellar calcium dependent nitric oxide synthase (NOS)
      activity, probably correlated to the motor abnormalities and the disarrangement
      in the cerebellar cytoarchitecture observed in adult rats. This decrease in
      calcium dependent NOS activity could be associated with an increased protein
      kinase C (PKC) activity. PKC inhibition partially restores calcium dependent NOS
      activity, indicating that PKC activity could be negatively modulating the
      catalytic activity of calcium dependent NOS. These findings suggest that a
      decrease in nitric oxide (NO) production and the related increase in PKC activity
      could be intracellular events that participate in the onset of motor and
      cerebellar abnormalities induced by postnatal gamma-irradiation at early stages
      of life.

PMID- 15993388
TI  - Structural investigation of lipopolysaccharides from nontypeable Haemophilus
      influenzae: investigation of inner-core phosphoethanolamine addition in NTHi
      strain 981.
AB  - LPS of NTHi comprises a conserved tri-l-glycero-D-manno-heptosyl inner-core
      moiety (l-alpha-D-Hepp-(1-->2)-[PEtn-->6]-l-alpha-D-Hepp-(1-->3)-[beta-D-Glcp-(1-
      >4)]-l-alpha-D-Hepp-(1-->5)-alpha-Kdop) in which addition of PEtn to the central
      heptose (HepII) in strain Rd is controlled by the gene lpt6. It was recently
      shown that NTHi strain 981 contains an additional PEtn linked to O-3 of the
      terminal heptose of the inner-core moiety (HepIII). In order to establish whether
      lpt6 is also involved in adding PEtn to HepIII, lpt6 in strain 981 was
      inactivated. The structure of the LPS of the resulting mutant strain 98llpt6 was
      investigated by MS and NMR techniques by which it was confirmed that the lpt6
      gene product is responsible for addition of PEtn to O-6 of HepII in strain 981.
      However, it is not responsible for adding PEtn to O-3 of HepIII since the 981lpt6
      mutant still had full substitution with PEtn at HepIII.

PMID- 15993389
TI  - Characterisation of a 1,4-beta-fucoside hydrolase degrading colanic acid.
AB  - A novel colanic acid-degrading enzyme was isolated from a mixed culture filtrate
      obtained by enrichment culturing of a compost sample using colanic acid as carbon
      source. The enzyme was partially purified resulting in a 17-fold increase in
      specific activity. Further purification by Native PAGE revealed that the enzyme
      is part of a high-molecular weight multi protein complex of at least six
      individual proteins. The enzyme showed a temperature optimum at 50 degrees C
      while after 5h at 50 degrees C and pH7 still 70% of the total activity was left.
      The pH optimum was found to be pH7. Analysis of the degradation products showed
      that the enzyme is a novel 1,4-beta-fucoside hydrolase that liberates repeating
      units of colanic acid with varying degrees of acetylation. Km and Vmax of the
      enzyme were determined against the native substrate as well as its de-O
      acetylated and depyruvated forms. Compared to the native substrate the affinity
      of the enzyme for the modified substrates was much lower. However, for the de-O
      acetylated sample a dramatic increase in catalytic efficiency was observed. The
      native form of the substrate showed substrate inhibition at high concentrations,
      probably due to the formation of nonproductive substrate complexes. Removal of
      the acetyl groups probably prevents this effect resulting in a higher catalytic
      efficiency.

PMID- 15993390
TI  - Mechanisms of atrial natriuretic peptide secretion from the atrium.
AB  - Since the discovery of atrial natriuretic peptide (ANP) more than 20 years ago,
      numerous studies have focused on the mechanisms regulating ANP secretion. From a
      physiological standpoint, the most important factor governing ANP secretion is
      mechanical stretching of the atria, which normally occurs when extracellular
      fluid volume or blood volume is elevated. In addition, the ability of several
      vasoconstrictors to increase ANP secretion can be traced to their indirect
      effects on atrial stretch via increases in cardiac preload or afterload. Whether
      vasoconstrictors such as angiotensin II and vasopressin have a direct positive or
      negative effect on ANP secretion has not been determined with certainty. Two
      paracrine factors derived from endothelial cells play important roles in
      modulating ANP secretion. Endothelin, a potent vasoconstrictor, stimulates ANP
      secretion and augments stretch induced ANP secretion. The dramatic increase in
      ANP release produced by cardiac ischemia appears to be mediated in part by
      endothelin. Nitric oxide (NO), an important vasodilator, is also produced by
      endothelial cells and inhibits ANP secretion acting through cyclic GMP as an
      intracellular messenger. Several recent studies have helped to define the
      cellular mechanism contributing to regulation of ANP secretion including stretch
      activated ion channels, prostaglandins, cytochrome P450, G proteins and cell
      calcium. A number of steps in the cellular transduction of the ANP signal remain
      to be resolved. The release of ANP in disease states such as myocardial
      infarction and heart failure appears to be related to both mechanical and
      cellular events.

PMID- 15993391
TI  - Adaptation of alpha-fetoprotein and intact human chorionic gonadotropin
      fluoroimmunometric assays to dried blood spots.
AB  - BACKGROUND: Although dried blood spots (DBS) are very convenient for massive
      screening, there are very few examples of their application in maternal serum
      screening of Down's syndrome and neural tube defects. For large-scale mass
      population screening in Brazil, a continental country, DBS would be fairly
      recommended. As there are no easily available commercial assays of AFP and hCG in
      DBS, the Wallac Delfia fluoroimmunometric assays intended for these biochemical
      markers were adapted to DBS. METHODS: Serum specimens and DBS obtained from 116
      pregnant women were analyzed by conventional methodology and by the adapted
      assays, respectively. Precision (within-run and between-run), recovery and
      detection limits studies were conducted RESULTS: The non-linear regression fit of
      the levels of AFP and hCG in DBS by gestational age in days was described. There
      was a strong statistically significant correlation between the levels of these
      analytes in serum specimens and in DBS. For both analytes, the precision
      variances were compared to those presented by the manufacturer for serum samples.
      CONCLUSION: It is feasible to use these DBS adapted assays in maternal serum
      screening programs.

PMID- 15993392
TI  - Oxidized low density lipoproteins, statin therapy and severity of coronary artery
      disease.
AB  - BACKGROUND: The impact of statin therapy on the association between circulating
      levels of oxidized low density lipoproteins (OxLDL) and severity of coronary
      artery disease (CAD) has not been studied. METHODS: OxLDLs were measured in 687
      patients with angiographically proven CAD (320 patients, 46.6% on statin therapy
      and 367 patients, 53.4% not on statin therapy on admission) using the Mercodia
      Oxidized LDL Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Patients on
      statin therapy had lower levels of OxLDL (median [interquartile range]; 63.9 U/L
      [53.9; 79.8] versus 72.3 U/L [58.4; 86.1], P<0.001) and C-reactive protein (3.0
      mg/L [1.2; 6.6] versus 4.0 mg/L [1.7; 13.1], P<0.001) than patients not on
      statins. Multivariable analysis showed that statin therapy was an independent
      predictor of lower levels of OxLDL (P=0.0001). In univariate analysis, OxLDL
      level did not differ significantly among the patients with 1-, 2-or 3-vessel
      disease (70.5 U/L [57.5; 85.6], 66.3 U/L [53.8; 82.6] and 68.2 U/L [57.0; 83.4],
      respectively, P=0.26). Multivariable logistic regression analysis showed that
      OxLDL was an independent correlate of angiographic severity of CAD (P=0.04) and
      that there was an interaction (P=0.038) between statins and OxLDL in that the
      increased levels of OxLDL were associated with more extensive CAD. CONCLUSION:
      Patients with CAD who receive statins have lower levels of OxLDL and an
      attenuation of the relationship between circulating levels of OxLDL and CAD
      severity compared with patients who do not receive statins.

PMID- 15993393
TI  - Age dependent assessment of TFPI levels in follicular fluid of women undergoing
      IVF.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type
      serine proteinase inhibitor which plays a central role in the extrinsic pathway
      of blood coagulation. A significant role of TFPI for the follicular development
      has been discussed in recent studies, and thrombotic complications during IVF
      procedure are a common problem. To elucidate the pathophysiological mechanisms
      underlying these problems, we have measured TFPI levels in human follicular fluid
      (hFF) of women undergoing in vitro fertilisation (IVF). METHODS: Total TFPI
      concentrations were determined in hFF of 28 women undergoing IVF treatment, 6 of
      whom developed an ovarian hyperstimulation syndrome (OHSS). RESULTS AND
      CONCLUSIONS: This is the first study to demonstrate an age-dependance of TFPI
      concentrations in hFF. Additionally, TFPI levels in hFF of women developing OHSS
      were determined as 323+/-66.8 ng/mL (mean+/-SD) in comparison with 279+/-137
      ng/mL for non-OHSS patients. Our findings demonstrate that, unlike the decreased
      TFPI levels found in OHSS patients' blood, there is no statistically significant
      difference in hFF TFPI levels between OHSS and non-OHSS patients. Furthermore, we
      could show that the outcome of the IVF procedure is not correlated with TFPI
      levels in hFF.

PMID- 15993394
TI  - Detecting AFP mRNA in peripheral blood of the patients with hepatocellular
      carcinoma, liver cirrhosis and hepatitis.
AB  - BACKGROUND: The low frequency of disseminated carcinoma cells in the blood now
      makes immunomagnetic bead sorting and reverse transcriptase-polymerase chain
      reaction (RT-PCR) technique more popular. METHODS: Three milliliters of
      peripheral blood were collected from 91 patients and 18 normal donors. The
      circulating carcinoma cells were enriched with CD45 and Ber-EP4 immunomagnetic
      beads. The alpha-fetoprotein (AFP) mRNA was amplified with nested RT-PCR.
      RESULTS: The total positive detection rate was 72.1%, 43.8%, 25.0%, 100%, and
      66.7% in patients with hepatocellular carcinoma (HCC) untreated, liver cirrhosis
      (LC), hepatitis, metastasis liver cancer, and postsurgery of hepatocellular
      carcinoma, respectively. There was a significant difference among the patients
      with HCC, LC and hepatitis (HCC vs. LC, P<0.05; HCC vs. hepatitis, P<0.01) and
      between Class A and B of the HCC patients (P<0.05). Meanwhile, AFP mRNA was
      markedly expressed in HCC patients compared to the patients with no HCC (LC and
      hepatitis). The levels of aspartate transaminase (AST) and gamma
      glutamyltranspeptidase (GGT) were significantly different in AFP mRNA-positive
      patients with autoimmune chronic active hepatitis B (CAHB) or LC in contrast to
      the corresponding negative patients. CONCLUSION: Combining negative and positive
      immunomagnetic bead sorting and RT-PCR technique can effectively detect
      circulating tumor cells. AFP mRNA is a more reliable marker of metastasis
      compared to serum AFP.

PMID- 15993395
TI  - Development of immunoassays for serum tartrate-resistant acid phosphatase isoform
      5a.
AB  - BACKGROUND: Serum tartrate-resistant acid phosphatase (TRACP) consists of 2
      structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing
      osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a
      novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a
      activity and protein. METHODS: Biotinylated anti-TRACP antibodies were used to
      immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl
      phosphate as substrate. TRACP 5a protein was measured with an independent
      peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for
      linearity of serum dose response, sensitivity and precision. Reference ranges for
      TRACP 5a were established from serum of 50 healthy males and 50 healthy age
      matched females. Serum TRACP 5a activity and protein were determined in 29 cases
      of rheumatoid arthritis. RESULTS: Serum matrix interference in both TRACP 5a
      assays required dilution to 10% serum to approach linearity. Intra-assay and
      inter-assay CV% were <10%. Mean serum TRACP 5a activity and protein were
      significantly higher in healthy men than women. There was a slight, but
      significant age related increase in both serum TRACP 5a and 5b among females, but
      not males, from age 20 to 70 years. TRACP 5a activity was positively correlated
      to TRACP 5a protein in healthy sera. Neither TRACP 5a activity nor protein was
      correlated strongly to TRACP-5b activity. TRACP 5a protein was significantly
      increased in 8/29 RA sera, whereas TRACP 5a and 5b activities were not. TRACP 5a
      activity and protein were not significantly correlated in RA sera. CONCLUSIONS:
      Although TRACP 5a and 5b are related biosynthetically, their circulating levels
      in healthy humans were independent, suggesting differential regulation of
      expression. In chronic diseases, increased TRACP 5a may represent pathological
      processes of inflammation unrelated to bone metabolism.

PMID- 15993396
TI  - Beware of multiple comparisons: a study of symptoms associated with mutations of
      the HFE hemochromatosis gene.
AB  - BACKGROUND: Studies involving a large number of comparisons have a high
      likelihood of finding statistically significant associations by chance alone
      (Type 1 error). Genetic association studies are particularly prone to this
      pitfall. We tested the effect of multiple comparisons in a study of symptoms
      among subjects genotyped for mutations of the HFE hemochromatosis gene. METHODS:
      Two randomly selected groups were created from a dataset of 30,917 white adult
      subjects genotyped for the C282Y and H63D mutations of the HFE gene. Frequency of
      symptoms among subjects with different HFE genotypes was compared to sex-matched
      wild type controls in Random Group 1 (hypothesis generation). Statistically
      significant associations (p<0.05 by chi2) were then tested in Random Group 2
      (hypothesis testing). RESULTS: A total of 101/1765 associations in men and
      116/2015 associations in women were statistically significant in Random Group 1.
      Of these, 12 associations in men and 13 associations in women were also
      statistically significant in Random Group 2, 11 of which were specific to
      hemochromatosis. None of the remaining 14 associations (6 in men and 8 in women)
      involved symptoms with a biologically plausible relationship to hemochromatosis
      or iron overload. CONCLUSIONS: Genetic association studies should be scrutinized
      for the possibility of Type 1 error.

PMID- 15993397
TI  - Influence of renal function on N-terminal pro-brain natriuretic peptide (NT
      proBNP) in patients admitted for dyspnoea in the Emergency Department: comparison
      with brain natriuretic peptide (BNP).
AB  - BACKGROUND: Renal dysfunction influences the optimum brain natriuretic peptide
      (BNP) threshold for a diagnosis of cardiac-related dyspnoea, but this has not
      been demonstrated for N-terminal pro-brain natriuretic peptide (NT-proBNP). We
      studied the influence of renal function on NT proBNP and BNP concentrations in
      dyspnoeic patients admitted by night to the Emergency Department (ED). METHODS:
      NT-proBNP, BNP, and creatinine levels were measured in blood samples collected
      routinely from 381 patients; estimated glomerular filtration rate (eGFR) was
      calculated. RESULTS: Cardiac-related dyspnoea was found in 115 patients (30.2%).
      NT-proBNP and BNP values were elevated in patients with cardiac-related dyspnoea
      (6823+/-6569 vs. 2716+/-4838 pg/ml, and 642+/-329 vs. 243+/-267 pg/ml, p<0.0001,
      respectively). Log-transformed NT-proBNP and BNP values were correlated to eGFR
      values. Mean NT-proBNP and BNP values stratified by ED diagnosis increased in
      line with eGFR categories, but in each category both peptide concentrations
      remained elevated in cardiac-related dyspnoea when compared with non-cardiac
      related dyspnoea (p<0.05). NT-proBNP (and BNP) cut-off points rose as a function
      of eGFR categories: from 1360 (and 290) pg/ml in patients with eGFR 60-89
      ml/min/1.73 m2, to 6550 (and 515) pg/ml in patients with eGFR 15-29 ml/min/1.73
      m2. CONCLUSION: Renal function influences the optimal cut-off points of NT-proBNP
      and BNP for the diagnosis of cardiac-related dyspnoea.

PMID- 15993400
TI  - How to trigger elaborate processing? A comment on Kunde, Kiesel, and Hoffmann
      (2003).
AB  - Recently, [Kunde, W., Kiesel, A., & Hoffmann, J. (2003). Conscious control over
      the content of unconscious cognition. Cognition, 88, 223-242] used a masked
      priming paradigm to argue that neither the 'elaborate processing' or the
      'evolving automaticity' view can account for the processing of unconscious
      numerical stimuli. In our Experiment 1 we replicated [Kunde, W., Kiesel, A., &
      Hoffmann, J. (2003). Conscious control over the content of unconscious cognition.
      Cognition, 88, 223-242] Experiment 4 and show that with a less demanding mask
      than that used by Kunde et al., 'elaborate processing' can explain priming
      results given that there are side conditions to trigger elaborate processing of
      unconscious stimuli. The second experiment further explores this influence of the
      masks by increasing the relevance of the symbols by which the mask is composed.
      The results show that an increase in relevance of the mask is accompanied by a
      decrease in the priming effect, though there was no significant change in
      conscious awareness of the prime.

PMID- 15993398
TI  - Can infants attribute to an agent a disposition to perform a particular action?
AB  - The present research investigated whether 13.5-month-old infants would attribute
      to an actor a disposition to perform a recurring action, and would then use this
      information to predict which of two new objects-one that could be used to perform
      the action and one that could not-the actor would grasp next. During
      familiarization, the infants watched an actor slide various objects forward and
      backward on an apparatus floor. During test, the infants saw two new identical
      objects placed side by side: one stood inside a short frame that left little room
      for sliding; the other stood inside a longer frame that left ample room for
      sliding. The infants who saw the actor grasp the object inside the short frame
      looked reliably longer than those who saw the actor grasp the object inside the
      long frame. This and control results from a lifting condition provide evidence
      that by 13.5 months, infants can attribute to an actor a disposition to perform a
      particular action.

PMID- 15993401
TI  - On the fate of distractor stimuli in rapid serial visual presentation.
AB  - Observers demonstrate an impaired ability to report the second of two targets in
      a rapid serial visual presentation (RSVP) stream if it appears within 500 ms of
      the first target--a phenomenon known as the attentional blink. This study
      investigated the fate of stimuli in dual-target RSVP streams that do not require
      report--the distractors. In five experiments, observers viewed dual-target RSVP
      streams where the items flanking Target 1 either had the same identity (repeats)
      or a different identity (non-repeats). Repeated distractors reduced the
      attentional blink, but only if two conditions were met (1) the items flanking
      Target 1 were featurally identical and (2) the distractors were drawn from a
      different alphanumeric category to the targets (e.g. digits vs. letters). We
      interpret this reduced blink magnitude in the repeat trials as evidence that in
      RSVP streams distractor items that appear in close temporal proximity to Target 1
      are inhibited and we propose that this inhibition occurs both at the level of
      alphanumeric features and abstract identities.

PMID- 15993402
TI  - Measuring individual differences in sensitivities to basic emotions in faces.
AB  - The assessment of individual differences in facial expression recognition is
      normally required to address two major issues: (1) high agreement level (ceiling
      effect) and (2) differential difficulty levels across emotions. We propose a new
      assessment method designed to quantify individual differences in the recognition
      of the six basic emotions, 'sensitivities to basic emotions in faces.' We
      attempted to address the two major assessment issues by using morphing techniques
      and item response theory (IRT). We used morphing to create intermediate, mixed
      facial expression stimuli with various levels of recognition difficulty. Applying
      IRT enabled us to estimate the individual latent trait levels underlying the
      recognition of respective emotions (sensitivity scores), unbiased by stimulus
      properties that constitute difficulty. In a series of two experiments we
      demonstrated that the sensitivity scores successfully addressed the two major
      assessment issues and their concomitant individual variability. Intriguingly,
      correlational analyses of the sensitivity scores to different emotions produced
      orthogonality between happy and non-happy emotion recognition. To our knowledge,
      this is the first report of the independence of happiness recognition, unaffected
      by stimulus difficulty.

PMID- 15993403
TI  - Categorical perception of speech sounds in illiterate adults.
AB  - Children affected by dyslexia exhibit a deficit in the categorical perception of
      speech sounds, characterized by both poorer discrimination of between-category
      differences and by better discrimination of within-category differences, compared
      to normal readers. These categorical perception anomalies might be at the origin
      of dyslexia, by hampering the set up of grapheme-phoneme correspondences, but
      they might also be the consequence of poor reading skills, as literacy probably
      contributes to stabilizing phonological categories. The aim of the present study
      was to investigate this issue by comparing categorical perception performances of
      illiterate and literate people. Identification and discrimination responses were
      collected for a /ba-da/ synthetic place-of-articulation continuum and between
      group differences in both categorical perception and in the precision of the
      categorical boundary were examined. The results showed that illiterate vs.
      literate people did not differ in categorical perception, thereby suggesting that
      the categorical perception anomalies displayed by dyslexics are indeed a cause
      rather than a consequence of their reading problems. However, illiterate people
      displayed a less precise categorical boundary and a stronger lexical bias, both
      also associated with dyslexia, which might, therefore, be a specific consequence
      of written language deprivation or impairment.

PMID- 15993404
TI  - Male and female germline specific expression of an EGFP reporter gene in a unique
      strain of transgenic rats.
AB  - A rat line was generated in which genomic integration of a ROSA-EGFP transgene
      resulted in exclusive expression of EGFP in the germ cells of both sexes. EGFP
      expression was uniform and robust in cleavage stage embryos beginning at the late
      2-cell stage and continuing through blastocyst development where expression
      became restricted to cells of the inner cell mass. Subsequent analysis showed
      high EGFP expression exclusively in primordial, embryonic, and adult germ cells.
      This unique expression pattern makes this EGFP marked locus the first molecular
      marker of the germline lineage in both sexes in mammals. FISH was used to
      localize the transgene insertion to chromosome 11q11-q12, proximal to Grik1 and
      near Ncam2. Analysis of the region did not identify known germ cell-specific
      genes but did identify 19 ESTs or transcribed loci present in testes, ovary, or
      pre-implantation libraries from mice or rats. To assess the utility of the
      transgenic line for germ cell transplantation studies, non-selected, freshly
      isolated seminiferous tubule cells were transferred to the testis of recipient
      males. The donor cell population colonized the testis at a surprisingly high
      efficiency within 30 days following transfer. Since EGFP is a vital marker, the
      colonization process can be followed in vivo and the extent of colonization
      quantified. The unique germ cell specific expression of EGFP makes this line of
      transgenic rats an excellent novel tool to study germ cell origin, development,
      and differentiation, and to assess the plasticity of adult somatic stem cells to
      become male germ cells.

PMID- 15993405
TI  - In vivo analysis of mRNA stability using the Tet-Off system in the chicken
      embryo.
AB  - The rate of mRNA degradation plays an important role in the control of gene
      expression. The mRNA stability is mainly dependent on cis-regulatory elements
      contained in the 3' or 5' untranslated region (UTR) of the mature mRNAs, and its
      regulation is an efficient way to adapt the level of a given transcript in the
      cell. Although this process has been well studied in cell culture, little is
      known about mRNA stability during embryonic development. Here, we describe an
      assay that combines the tetracyclin-dependent inducible system Tet-Off with in
      ovo electroporation to monitor mRNA stability in the chick neural tube. We show,
      by using the GFP intensity as an indirect reporter system, that the 3'UTR of
      Lunatic Fringe strongly destabilizes transcripts, while transcripts bearing the
      3'UTR of Fgf8 are much more stable. This simple assay provides a powerful tool to
      study mRNA dynamics in vivo.

PMID- 15993406
TI  - Glutathione is required for growth and prespore cell differentiation in
      Dictyostelium.
AB  - Glutathione (GSH) is the most abundant non-protein thiol in eukaryotic cells and
      acts as reducing equivalent in many cellular processes. We investigated the role
      of glutathione in Dictyostelium development by disruption of gamma
      glutamylcysteine synthetase (GCS), an essential enzyme in glutathione
      biosynthesis. GCS-null strain showed glutathione auxotrophy and could not grow in
      medium containing other thiol compounds. The developmental progress of GCS-null
      strain was determined by GSH concentration contained in preincubated media before
      development. GCS-null strain preincubated with 0.2 mM GSH was arrested at mound
      stage or formed bent stalk-like structure during development. GCS-null strain
      preincubated with more than 0.5 mM GSH formed fruiting body with spores, but
      spore viability was significantly reduced. In GCS-null strain precultured with
      0.2 mM GSH, prestalk-specific gene expression was delayed, while prespore
      specific gene and spore-specific gene expressions were not detected. In addition,
      GCS-null strain precultured with 0.2 mM GSH showed prestalk tendency and extended
      G1 phase of cell cycle. Since G1 phase cells at starvation differentiate into
      prestalk cells, developmental defect of GCS-null strain precultured with 0.2 mM
      GSH may result from altered cell cycle. These results suggest that glutathione
      itself is essential for growth and differentiation to prespore in Dictyostelium.

PMID- 15993407
TI  - Cyclooxygenase-2 in cancer cells and macrophages induces colon cancer cell growth
      by cigarette smoke extract.
AB  - Cigarette smoking, cyclooxygenase-2 (COX-2) and macrophages are independently
      associated with colorectal cancer. In the present study, cigarette smoke ethanol
      extract was applied to colon cancer cells (SW1116) or indirectly via activated
      macrophages (THP-1 cells) to attest their effects on cancer cell proliferation
      and tumor growth both in vitro and in vivo. Ethanol extract induced COX-2
      expression in SW1116 and THP-1 cells. Combination of THP-1 pre-incubated medium
      and ethanol extract further potentiated COX-2 expression and proliferation of
      SW1116 cells. Tumor growth in nude mice was positively associated with the medium
      and/or ethanol extract treatments, together with the up-regulation of cell
      proliferation and angiogenesis, and down-regulation of apoptosis. Application of
      a COX-2 inhibitor (SC236) reduced tumor growth as well as cell proliferation and
      angiogenesis. These actions are partially depended on the decrease of COX-2
      expression. Taken together, inhibition of COX-2 activity may have significant
      implication to prevent colon cancer in smokers.

PMID- 15993408
TI  - Establishment of two cell lines derived from conjunctival melanomas.

PMID- 15993409
TI  - Confocal laser Doppler flowmeter measurements in a controlled flow environment in
      an isolated perfused eye.
AB  - The aim of this study was to improve our ability to interpret and validate
      Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from
      specific regions of the retinal vasculature by taking advantage of the ability to
      precisely regulate perfusion flow in an isolated eye preparation. The retinal
      vasculature in 16 isolated perfused pig eyes was perfused with a 50%/50%
      Krebs/RBC solution at known flow rates ranging from 0 to 300 microl min(-1). At
      each flow rate, HRF images were obtained at a location approximately two disc
      diameters from the disc. After HRF image acquisition, the retinal vasculature was
      perfused with fluorescein isothiocyanate for fluorescence microscopy. Using the
      standard HRF software and a 10 x 10pixel measurement window, flow rates were
      measured from a retinal artery, vein, arteriole, venule, and the retinal
      capillary bed and a capillary-free-zone. The relationship between HRF measured
      flow and perfusion flow in the different measurement locations was determined. At
      zero perfusion flow the measured HRF flow was consistently greater than zero (
      approximately 170 arbitrary units (AU)), and not significantly different at each
      measurement location except for the retinal vein, which had a significantly
      higher HRF flow value ( approximately 230AU). At higher perfusion flow rates the
      flow signal from the larger vascular elements (arteries and veins) increased
      rapidly thereafter to reach several thousand AU at a total perfusate flow of 50
      microlmin(-1) and increased less rapidly at higher flow rates. In arterioles, the
      HRF flow was more linear over a broader range of perfusate flow rates but the
      peak flow signal was an order of magnitude smaller than that from the retinal
      artery. Both the linearity and magnitude of the flow signal in venules was less
      than that in arterioles. In capillary areas and in the capillary free zone, the
      HRF flow showed only a very weak relationship to perfusion flow when compared to
      the background noise. The choice of location for HRF flow analysis greatly
      influences the ability of the technique to measure changes in retinal blood flow.
      The major arteries and veins provide the strongest signal and greatest signal to
      noise ratio. However, the retinal arterioles produce an HRF signal that is more
      linear over a wider range of perfusate flow rates.

PMID- 15993410
TI  - Regulation of JAK2 protein expression by chronic, pulsatile GH administration in
      vivo: a possible mechanism for ligand enhancement of signal transduction.
AB  - Growth hormone (GH) is a key factor controlling postnatal growth and development.
      Despite growth-promoting effects in mammals, GH is not associated with muscle
      growth in the chicken. Janus kinase 2 (JAK2) has been identified as the first
      intracellular step in GH receptor (GHR) signaling in many species, however, there
      is limited knowledge regarding the GH signaling pathway in the chicken. In this
      study, GH-responsive, JAK2 immunoreactive proteins were first assessed in an
      avian hepatoma cell line (LMH). Tyrosine phosphorylation of a 120-122 kDa JAK2
      immunoreactive protein was GH dose-dependent. In addition to in vitro studies,
      the timecourse of JAK2 activation in liver and skeletal muscle (Pectoralis
      superficialis) in response to a single intravenous (i.v.) injection of chicken GH
      (cGH), and the effect of chronic exposure to GH in a physiologically relevant
      pattern on JAK2 protein expression and tyrosine phosphorylation in vivo were
      assessed. At a dose of GH that was previously demonstrated to elicit a maximal
      metabolic response (6.25 microg/kg BW), maximum tyrosine phosphorylation of JAK2
      appeared at 10 min post-GH administration in the pectoralis muscle, but was not
      detectable in liver. To assess whether chronic enhancement of GH would alter
      expression of JAK2, we utilized a dynamic model of pulsatile GH infusion that
      mimicked the early pattern of circulating GH expressed in younger, rapidly
      growing birds (high amplitude peaks with an inter-peak interval of 90 min). A 120
      122 kDa protein in liver and muscle, and a dominant 130-136 kDa protein in the
      muscle, that was phosphorylated in response to GH, were specifically recognized
      by the JAK2 antibody. Chronic, pulsatile infusion of cGH into 8-week-old chickens
      was associated with increased abundance and tyrosine phosphorylation of JAK2
      protein in both liver and muscle (P < 0.05), which were GH dose-dependent, and
      mirrored previously reported biological responses for the same birds [Vasilatos
      Younken, R., Zhou, Y., Wang, X., McMurtry, J.P., Rosebrough, R.W., Decuypere, E.,
      Buys, N., Darras, V.M., Van Der Geyten, S., Tomas, F., 2000. Altered chicken
      thyroid hormone metabolism with chronic GH enhancement in vivo: Consequences for
      skeletal muscle growth. Journal of Endocrinology 166, 609-620.]. In summary (1)
      JAK2 immunoreactive proteins that associate with the GHR and are tyrosine
      phosphorylated in response to GH were identified in an avian hepatoma cell line
      and expressed in both GH responsive (liver) and "non-responsive" (skeletal
      muscle) tissues; (2) tyrosine phosphorylation of JAK2 occurred within minutes of
      exposure to a single i.v. injection of GH in vivo in muscle but not liver of 8
      week-old birds; and 3) there were GH dose-dependent increases in abundance of
      JAK2 protein and tyrosine phosphorylation in both tissues when chronically
      exposed to GH in a physiologically relevant pattern, that mirrored dose-dependent
      biological responses, including alterations in the pathway of thyroid hormone
      metabolism, previously reported. Enhanced JAK2 suggests one possible mechanism
      whereby chronic, physiologically appropriate exposure to the ligand enhances GH
      biological action via increased abundance of a key upstream component of the
      signal transduction pathway.

PMID- 15993412
TI  - A neural network model for reconstructing EMG signals from eight shoulder
      muscles: consequences for rehabilitation robotics and biofeedback.
AB  - This paper demonstrates the ability of a fully connected feed forward neural
      network (FFNN) using the backpropagation training algorithm to predict the
      electromyography (EMG) signal from eight muscles of the shoulder for both
      exercises not used for training and EMG signals from subjects not used for
      training. The network showed a good predictive ability for subjects not used for
      training (r(2) between 0.33 and 0.84) and for activities not used for training
      (r(2) between 0.56 and 0.89). This may have applications for patients, physical
      therapists and doctors to monitor patient performance by reviewing the level of
      agreement between the patient EMG and the predicted EMG. Coupled with traditional
      methods of evaluation, EMG can provide an excellent measure of how well a patient
      has responded or is responding to treatment. Incorporating robotic technology
      could facilitate the use of EMG as an input to an intelligent decision making
      algorithm used to increase or decrease the level of difficulty according to
      patient performance.

PMID- 15993414
TI  - A three-dimensional finite element analysis of the combined behavior of ligaments
      and menisci in the healthy human knee joint.
AB  - We present here a three-dimensional FE model of the healthy human knee that
      included the main structures of the joint: bones, all the relevant ligaments and
      patellar tendon, menisci and articular cartilages. Bones were considered to be
      rigid, articular cartilage and menisci linearly elastic, isotropic and
      homogeneous and ligaments hyperelastic and transversely isotropic. Initial
      strains on the ligaments and patellar tendon were also considered. This model was
      validated using experimental and numerical results obtained by other authors. Our
      main goal was to analyze the combined role of menisci and ligaments in load
      transmission and stability of the human knee. The results obtained reproduce the
      complex, nonuniform stress and strain fields that occur in the biological soft
      tissues involved and the kinematics of the human knee joint under a physiological
      external load.

PMID- 15993413
TI  - Osteocyte lacunae tissue strain in cortical bone.
AB  - Current theories suggest that bone modeling and remodeling are controlled at the
      cellular level through signals mediated by osteocytes. However, the specific
      signals to which bone cells respond are still unknown. Two primary theories are:
      (1) osteocytes are stimulated via the mechanical deformation of the perilacunar
      bone matrix and (2) osteocytes are stimulated via fluid flow generated shear
      stresses acting on osteocyte cell processes within canaliculi. Recently, much
      focus has been placed on fluid flow theories since in vitro experiments have
      shown that bone cells are more responsive to analytically estimated levels of
      fluid shear stress than to direct mechanical stretching using macroscopic strain
      levels measured on bone in vivo. However, due to the complex microstructural
      organization of bone, local perilacunar bone tissue strains potentially acting on
      osteocytes cannot be reliably estimated from macroscopic bone strain
      measurements. Thus, the objective of this study was to quantify local perilacunar
      bone matrix strains due to macroscopically applied bone strains similar in
      magnitude to those that occur in vivo. Using a digital image correlation strain
      measurement technique, experimentally measured bone matrix strains around
      osteocyte lacunae resulting from macroscopic strains of approximately 2000
      microstrain are significantly greater than macroscopic strain on average and can
      reach peak levels of over 30,000 microstrain locally. Average strain
      concentration factors ranged from 1.1 to 3.8, which is consistent with analytical
      and numerical estimates. This information should lead to a better understanding
      of how bone cells are affected by whole bone functional loading.

PMID- 15993415
TI  - Surface complexation of condensed phosphate to aluminum hydroxide: an ATR-FTIR
      spectroscopic investigation.
AB  - Two model compounds, sodium pyrophosphate (pyro-P) and sodium tripolyphosphate
      (tripoly-P), were employed to elucidate the binding mechanisms of condensed
      phosphate on aluminum hydroxide by utilizing attenuated total reflectance-Fourier
      transform infrared (ATR-FTIR) spectroscopy. Peak assignments for the condensed
      phosphates in the solution phase and those adsorbed on the surface of aluminum
      hydroxide were made. Electron delocalization and polarization were employed to
      explain the peak shifts and the complexation of condensed phosphate with aluminum
      hydroxide. The tripoly-P and pyro-P were adsorbed on aluminum hydroxide by
      forming inner-sphere complexes. The adsorbed condensed phosphates were
      deprotonated in the pH range from 4 to 10. Monodentate, bidentate, and binuclear
      complexes were formed when pyro-P was adsorbed on aluminum hydroxide, while
      monodentate and binuclear complexes were formed when tripoly-P was adsorbed.
      Based on the FTIR data, we proposed that when either bidentate or binuclear
      complexes were formed, the two oxygen atoms participating in the complexation
      with aluminum hydroxide could not be originated from the same terminal phosphate
      moiety. The AlO bond formed in the complexation of pyro-P or tripoly-P with
      aluminum hydroxide (AlPO(-3)) was not as strong as the HO bond in terminal HPO(
      3). The bridging PO(-2) of tripoly-P did not coordinate with aluminum hydroxide.
      The real-time ATR-FTIR study on condensed phosphate adsorption revealed that a
      long contact time between condensed phosphates and aluminum hydroxide particles
      can result in a transformation of an initially formed species into a
      thermodynamically more stable phase.

PMID- 15993416
TI  - The role of adsorption compression in nanocapillarity.
AB  - Influence of adsorption compression on nanocapillarity is discussed. Kelvin's
      equation for a compressible liquid is written in a form that takes into account
      not only Laplace's pressure, but also adsorption compression. This leads to a
      simple analytical equation for pressure in nanocapillaries. It is shown that the
      ratio of Laplace's pressure to the adsorption compression pressure determines
      different types of nanocapillary behavior. When the Laplace pressure dominates,
      it results in classical capillarity that is well studied and understood. There is
      an intermediate range where Laplace's pressure is partially or fully compensated
      by adsorption compression, and the resulting pressure in a capillary is an
      interplay between attraction to walls and repulsions from neighboring molecules
      in compressed adsorbed fluid. If the adsorption compression pressure dominates,
      it results in inversion of capillary pressure and the fluid adsorbed in the
      nanocapillary presses on walls from inside. This phenomenon has been observed
      experimentally for fluids in nanoporous solids; in particular, high-precision
      measurements have shown significant expansion of nanoporous adsorbents loaded
      with various fluids. It is also shown that oscillatory adhesion forces and
      internal forces in nanoporous adsorbents have a common thermodynamic origin and
      can be discussed in the framework of adsorption compression mechanisms.

PMID- 15993417
TI  - Biosorbent for tungsten species removal from water: effects of co-occurring
      inorganic species.
AB  - The effect of co-occurring inorganic species on the removal of tungsten from
      water was investigated using biosorbent (i.e., chitosan coated montmorillonite
      clay). Simulated natural water and well water from Fallon, NV were used for this
      study. The concentrations of tungsten (21-541 mg/L) and inorganic species
      ([H(2)CO(3)]=0-4.2 mg/L, [H(4)SiO(4)]=0-90 mg/L, and [SO(2-)(4)]=0-400 mg/L) in
      simulated feed water were varied. The concentration of tungsten in the well water
      was 26 microg/L. The pH level of simulated feed water and well water was adjusted
      to 4 since this pH was found to be the most effective pH for the tungsten removal
      using chitosan coated clay. Tungsten removal without the existence of co
      occurring inorganic species decreases from 99.8 to 87.1% with an increase in
      initial tungsten concentration from 21 to 541 mg/L. It reduces further as the co
      occurring inorganic species concentration increases. The percentage of the
      tungsten removal ranges between 68.2-93.8%, 66.7-94.2%, and 53.6-93.7% for
      simulated natural water containing varied amount of H(2)CO(3), H(4)SiO(4), and
      SO(2-)(4), respectively. The adsorption kinetic data could be best described by
      the pseudo second order expression. The adsorption equilibrium data was modeled
      with the Langmuir, Temkin, and Freundlich equations and was found to be
      represented well by the Langmuir equation. The essential characteristics of the
      Langmuir isotherm indicate that the adsorption of tungsten on chitosan coated
      clay is favorable regardless of the presence of interfering species. Compared to
      natural clay, chitosan coated clay has about 116 times larger adsorption capacity
      per gram of chitosan, which makes it a superior adsorbent. However, the maximum
      tungsten adsorption capacity decreases in the presence of co-occurring species
      since the co-occurring species suppress the adsorption. For the well water
      treated with biosorbent, the tungsten concentration in the product water was
      found to be lower than the detection limit (1 microg/L) of the inductively
      coupled plasma mass spectrometer (ICP-MS). The repeatable results obtained from
      the treatment of both simulated and well water suggest that using chitosan coated
      clay can be an efficient adsorbent for tungsten removal from contaminated sites.

PMID- 15993418
TI  - The influence on paper strength properties when building multilayers of weak
      polyelectrolytes onto wood fibres.
AB  - Polyallylamine hydrochloride (PAH) and polyacrylic acid (PAA) have been used to
      build up polyelectrolyte multilayers (PEM) on wood fibres and on silicon oxide
      surfaces, under various pH conditions. Consecutive adsorption onto silicon oxide
      surfaces of PAH and PAA were studied using stagnation point adsorption
      reflectometry, and the results showed a steady build-up of multilayers.
      Furthermore, by altering pH, the build-up of the multilayer could be made either
      linear or exponential in terms of adsorbed amount. Nitrogen analysis of sheets
      prepared from modified fibres showed that the adsorbed amount of PAH increased
      throughout PEM build-up, the amount of increase depending on pH during
      adsorption. Strength measurements of the sheets, i.e., stress at break and strain
      at break, showed significant improvements ranging from 60 to 200%, depending on
      both pH during adsorption and type of polyelectrolyte in the outer layer. A good
      correlation between the adsorbed amount of PAH and the improved strength
      properties of the paper was also found.

PMID- 15993419
TI  - Isolation of viable antigen-specific CD4 T cells by CD40L surface trapping.
AB  - A number of techniques have recently been developed for the identification of
      antigen-specific cells, yet the ability of these techniques to identify all
      subclasses of memory T cells has often been overlooked. Here we describe a novel
      approach for the isolation of live antigen-specific CD4 T cells using CD40L and
      CD69 surface staining and demonstrate its utility for isolating antigen-specific
      rhesus macaque CD4 T cells. Critical to the success of the technique was staining
      for CD40L concurrent with antigen stimulation. Isolation of CD4 T cells based on
      CD40L/CD69 surface marker upregulation identified both effector and central
      memory CD4 T cells. In contrast, the majority of central memory CD4 T cells did
      not secrete TNFalpha or IFNgamma and thus would not be identified by techniques
      based on their secretion. The methodology described here therefore complements
      existing approaches for isolating viable antigen-specific CD4 T cells, opens new
      avenues for investigating human diseases in nonhuman primate animal models and
      may prove beneficial in instances where the induced response is largely T cell
      central memory restricted.

PMID- 15993420
TI  - Transcriptional pausing in vivo: a nascent RNA hairpin restricts lateral
      movements of RNA polymerase in both forward and reverse directions.
AB  - Transcriptional pausing by RNA polymerase has been the subject of extensive
      investigations in vitro, yet little is known about its occurrence and
      significance in vivo. The transient nature of the pausing events makes them
      difficult to observe inside the cell, whereas their studies in vitro by classical
      biochemical methods are usually conducted under non-physiological conditions that
      increase the pause duration. Here, we have used an Escherichia coli system in
      which several RNA polymerase molecules transcribing in tandem traverse a pausing
      sequence while approaching a protein roadblock. The in vivo DNA footprinting and
      RNA 3' end mapping of the elongation complexes are consistent with a dynamic view
      of the pausing event, during which RNA polymerase first loses its lateral
      stability and slides backward, and is subsequently rescued from extended
      backtracking and stabilized at the pause site by a nascent RNA hairpin. Our
      results show also that the folding of the hairpin provides an assisting force
      that promotes forward translocation of a trailing polymerase under a strained
      configuration by balancing the opposing force created by a steric clash with a
      leading elongation complex.

PMID- 15993421
TI  - A toy model for predicting the rate of amyloid formation from unfolded protein.
AB  - We develop a toy model for predicting the rate of amyloid formation from an
      unfolded polypeptide. The model assumes irreversible amyloid growth, employs a
      collision encounter scheme and uses a Gaussian chain approximation to describe
      the polypeptide sequence. A principal feature of the model is its dependence on a
      number of key sequence residues whose correct placement, geometric arrangement
      and orientation in relation to their interacting partners define the success, or
      otherwise, of the amyloid formation reaction. Although not realistic at the
      molecular level, the model captures some essential features of the system and is
      therefore useful from a heuristic standpoint. For the case of amyloid formation
      from an unstructured state, the model suggests that the major determinants of the
      rate of fibril formation are the length of the sequence separating the critical
      amino acids promoting amyloid formation and the positional placement of the
      critical residues within the sequence. Our findings suggest also that the
      sequence distance between the key interacting amino acid residues may play a role
      in defining the maximum width of a fibril and that the addition of non
      interacting segments of long structure-less polypeptide chain to an amyloidogenic
      peptide may act to inhibit fibril formation. We discuss these findings with
      reference to the placement of critical sequence residues within the polypeptide
      chain, the design of polypeptides with lower amyloid formation propensities and
      the development of aggregation inhibitors as potential therapeutics for protein
      depositional disorders.

PMID- 15993422
TI  - Site-directed spin labeling studies reveal solution conformational changes in a
      GAAA tetraloop receptor upon Mg(2+)-dependent docking of a GAAA tetraloop.
AB  - The Mg(2+)-dependent GAAA tetraloop interaction with its 11 nucleotide receptor
      is one of the most frequently occurring long-range tertiary interactions in RNAs.
      To explore conformational changes in the receptor during tetraloop docking,
      nitroxide spin labels were attached at each of four uridine bases, one at a time,
      within an RNA molecule containing the receptor sequence. In the presence of Mg2+
      and the tetraloop, the electron paramagnetic resonance (EPR) spectrum of one of
      the labeled bases reflected a large increase in mobility, indicating unstacking
      of the base upon tetraloop docking. This provides direct evidence that base
      unstacking is an intrinsic feature of the solution tetraloop-receptor complex
      formed in the presence of Mg2+. Additional evidence suggests that in solution the
      bound receptor conformation is similar to that observed in the crystal structure
      of a group I intron ribozyme domain. In Mg2+ alone, a receptor conformation with
      an unstacked base was not detectable, suggesting that this conformation is of
      higher standard state free energy than that of the free receptor. This leads to
      the conclusion that the extensive RNA-RNA interactions observed in the crystal
      structure of the tetraloop-receptor complex provide larger interaction energy
      than the measured apparent affinity between the tetraloop and the free receptor.
      This is compatible with a high specificity of the tetraloop-receptor interaction.

PMID- 15993423
TI  - The effect of migration on metapopulation stability is qualitatively unaffected
      by demographic and spatial heterogeneity.
AB  - Coupled map lattices (CMLs), using two coupled logistic equations, have been
      extensively used to model the dynamics of two-patch ecological systems. Such
      studies have revealed that migration rate plays an important role in determining
      the dynamics of the system, particularly when the two maps differ in their
      intrinsic growth rate parameter, r. However, under more realistic assumptions, a
      metapopulation can be expected to consist of more than two subpopulations, each
      with its own demographic parameters, which will in part be a function of the
      environment of that patch. The role of the spatial arrangement of heterogeneous
      (i.e. with different r values) subpopulations in shaping the dynamics of such a
      metapopulation has rarely been investigated. Here, we study the effect of
      demographic and spatial heterogeneity on the stability of one- and two
      dimensional systems of 64 coupled Ricker maps with different r values, under
      periodic and absorbing boundary conditions. We show that the effects of migration
      rate on metapopulation stability do not depend upon either the precise spatial
      arrangement of the subpopulations in the lattice, or on the presence of a
      moderate proportion of vacant (uninhabitable) patches in the lattice. The
      results, thus, suggest that metapopulation models are robust to variation in
      spatial arrangement of patch quality and, hence, of demographic parameters. We
      also show that for any given arrangement of the patches, maximum stability of the
      metapopulation occurs when the migration levels are intermediate, a result that
      agrees well with previous studies on two-map CML systems.

PMID- 15993424
TI  - The evolution of anisogamy: the adaptive significance of damage, repair and
      mortality.
AB  - Classic theory on the evolution of anisogamy focuses on the trade-off between
      gamete productivity and provisioning and mechanisms associated with post-zygotic
      survival. In this article, the role of mortality acting on both zygotes and
      gametes is explored as a factor influencing the evolution of different sized
      gametes. In particular, variable mortality through differential survival or
      metabolic damage is shown to affect the persistence of isogamy, the evolution of
      more than two sexes and the evolution of anisogamy. Evolutionary stable isogamous
      states are shown to be locally unstable and disruptive selection can induce the
      evolution of anisogamy. Analysis of both the isogamous and anisogamous ESS points
      reveals that the persistence of either of these conditions is not always assured.
      The implications of variable survival on the evolution of anisogamy are
      discussed.

PMID- 15993425
TI  - Lipids, lipid rafts and caveolae: their importance for GPCR signaling and their
      centrality to the endocannabinoid system.
AB  - Scientific views of cell membrane organization are presently changing. Rather
      than serving only as the medium through which membrane proteins diffuse, lipid
      bilayers have now been shown to form compartmentalized domains with different
      biophysical properties (rafts/caveolae). For membrane proteins such as the G
      protein coupled receptors (GPCRs), a raft domain provides a platform for the
      assembly of signaling complexes and prevents cross-talk between pathways. Lipid
      composition also has a strong influence on the conformational activity of GPCRs.
      For certain GPCRs, such as the cannabinoid receptors, the lipid bilayer has
      additional significance. Endocannabinoids such as anandamide (AEA) are created in
      a lipid bilayer from lipid and act at the membrane embedded CB1 receptor.
      Endocannabinoids exiting the CB1 receptor are transported either by a carrier
      mediated or a simple diffusion process to the membrane of the postsynaptic cell.
      Following cellular uptake, perhaps via caveolae/lipid raft-related endocytosis,
      AEA is rapidly metabolized by a membrane-associated enzyme, fatty acid amide
      hydrolase (FAAH) located in the endoplasmic reticulum. The entry point for AEA
      into FAAH appears to be from the lipid bilayer. This review explores the
      importance of lipid composition and lipid rafts to GPCR signaling and then
      focuses on the intimate relationship that exists between the lipid environment
      and the endocannabinoid system.

PMID- 15993426
TI  - Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human
      cell lines.
AB  - Cytotoxic and antiproliferative effects of halothane, isoflurane, and sevoflurane
      in anesthetic doses on human colon carcinoma (Caco-2), larynx carcinoma (HEp-2),
      pancreatic carcinoma cells (MIA PaCa-2), poorly differentiated cells from lymph
      node metastasis of colon carcinoma (SW-620), and normal fibroblasts were
      investigated. Cells were exposed to anesthetic gas mixture consisting of O(2):
      N2O (35:60 vol.%), halothane (1.5 vol.%) or isoflurane (2.0 vol.%) or sevoflurane
      (3.0 vol.%), and CO(2) (5 vol.%), for 2, 4, and 6 h. Cytotoxicity of anesthetics
      was analyzed by validated tetrazolium dye assay MTT test. All anesthetics
      expressed cytotoxic effects on treated tumor cells in time and cell line
      dependent manner. Growth suppression in cells exposed to halothane was enhanced
      in HEp-2 (to 67.7%), Caco-2 (to 76.3%), and SW620 cells (to 80.9%), and was
      minimal in normal fibroblasts (to 89.4%). Antiproliferative activity of halothane
      was measured via radioactive precursors incorporation assay. In Caco-2 cells
      treated by halothane, decrease in DNA synthesis (52.4%, p=0.001), RNA synthesis
      (39.2%, p<0.001), and protein synthesis (19.2%, p=0.004) was observed. In HEp-2
      cells, DNA and RNA syntheses were decreased to 72.5% and 79.9%, whereas protein
      synthesis was 14.0% of control (p<0.001). In SW620 cells, protein synthesis after
      4 h was 24.4% (p=0.007). A DNA fragmentation was observed in Caco-2 and MIA PaCa
      2 cells. Exposition of phosphatidylserine on outer lipid bilayer plasma membrane
      of tumor cell treated by halothane proved apoptosis as mode of cell death.

PMID- 15993427
TI  - Recent developments in cannabinoid ligands.
AB  - Over the past 40 years, much research has been carried out directed toward the
      characterization of the cannabinergic system. With the identification of two G
      protein coupled receptors and the endogenous ligand, anandamide, pharmacological
      targets have expanded to encompass hydrolase and transport proteins as well as
      novel classes of cannabinoid ligands. Those ligands that demonstrate high
      affinity for the receptors and good biological efficacy are tied together through
      lipophilic regions repeatedly demonstrated necessary for activity. This review
      presents recent developments in the structure-activity relationships of several
      classes of cannabinoid ligands.

PMID- 15993428
TI  - Pharmacokinetic behavior in plasma, cerebrospinal fluid and cerebral cortex after
      intranasal administration of hydrochloride meptazinol.
AB  - The aim of this paper is to investigate the pharmacokinetic behavior of
      hydrochloride meptazinol (MEP) in plasma, cerebrospinal fluid (CSF) and cerebral
      cortex after intranasal administration (8 mg/kg) in male Sprague-Dawley rats. The
      pharmacokinetic study of intravenous administration (8 mg/kg) was also performed
      in rats. CSF and cerebral cortex samples were collected by serial CSF sampling
      and intracerebral microdialysis, respectively. The concentration of MEP in the
      biological samples was measured by high performance liquid chromatography (HPLC).
      It was determined that the absorption of MEP from the nasal cavity to systemic
      circulation was rapid and complete. The concentration-time profile showed a
      prolonged duration of MEP concentration in CSF and cortex following intranasal
      administration. The ratios of AUC values of intranasal to intravenous
      administrations were 0.96, 1.07 and 1.81 in plasma, CSF and cortex dialysate,
      respectively. In conclusion, intranasal administration of MEP is a promising
      alternative to traditional administration modes. Olfactory mucosa did not present
      intranasal MEP another pathway, in addition to systemic absorption, for transport
      to the brain.

PMID- 15993429
TI  - Unsuspected organic pollutants in marine mammals: halogenated naphthols.

PMID- 15993430
TI  - Copper bioavailability in a coastal environment of Northern Chile: comparison of
      bioassay and analytical speciation approaches.
AB  - An integrated approach including chemical speciation analyses and microalgal
      bioassays was used to assess the impact of copper from copper mining on a coastal
      area in Northern Chile. Dissolved copper ranged from <1 microg l(-1) at reference
      sites to 48 microgl(-1) at sites close to the mine discharge. Dissolved copper at
      sites closest to the discharge always exceeded seawater complexing capacities
      determined by anodic stripping voltammetry (ASV), and consequently labile copper
      was always detected (1-37 microg l(-1)). Agreement between ASV-labile copper and
      copper retained by cation exchange (ALSA) columns was excellent. Measured labile
      copper also accurately predicted bioavailable copper determined by growth
      inhibition of Nitzschia closterium and enzyme inhibition in Dunaliella
      tertiolecta. Seawater from Caleta La Lancha had the highest dissolved and labile
      copper and was the most toxic to micro-algal growth and enzyme activity. Previous
      studies at this site confirmed it had the lowest level of biodiversity,
      suggesting that copper may have both direct and indirect effects on these
      communities.

PMID- 15993431
TI  - Skin blood flowmotion response to insulin iontophoresis in normal subjects.
AB  - In order to explore the mechanisms directly involved in the insulin vasodilatory
      activity, we studied skin blood flowmotion by means of spectral analysis of the
      skin forearm laser Doppler (LD) signal registered before and after iontophoresis
      of insulin in saline (I.S.) (0.1 ml Humulin R 100 IU/ml diluted 1/10 in 0.9%
      saline) or pure saline (P.S.) (0.1 ml of 0.9% saline) in twenty normal subjects.
      Skin LD blood perfusion was also measured in conventional perfusion unit (PU; 1
      PU=10 mV). Using a Fast Fourier transform algorithm, power density (PD) of the
      total flowmotion spectrum, from 0.009 to 1.6 Hz, was measured in PU/Hz. Power
      density of five skin flowmotion frequency intervals (F.I.) within 0.009-0.02 Hz,
      0.02-0.06 Hz, 0.06-0.2 Hz, 0.2-0.6 Hz and 0.6-1.6 Hz (referred to endothelial,
      sympathetic, myogenic, respiratory and heart activity, respectively) was also
      measured in PU/Hz. The mean skin LD perfusion increment (expressed as percent
      change from baseline) was significantly higher after I.S. than after P.S.
      (P<0.001, ANOVA for repeated measures). Skin flowmotion total spectrum mean PD
      value significantly increased following iontophoresis of both P.S. (from 1.06+/
      0.62 to 1.86+/-0.94 PU/Hz, P<0.005) and I.S. (from 1.07+/-0.92 to 2.39+/-1.73
      PU/Hz P<0.00005), however, the mean PD increment was significantly higher after
      I.S. than after P.S. (1.27+/-0.98 PU/Hz versus 0.69+/-0.67 PU/Hz, P<0.05). Only
      the flowmotion component referred to myogenic activity showed a percent PD
      increase from baseline significantly higher in response to I.S. than to P.S.
      iontophoresis (114.5+/-21.8% versus 58.8+/-17.9%, respectively, P<0.05). These
      findings show that insulin has a vasodilatory activity on skin microvascular
      district. The higher increase of total blood flowmotion PD and particularly of
      the component related to the myogenic activity in response to insulin
      iontophoresis suggests that the cutaneous vasodilatory activity of insulin is, in
      part, related to an important action of this hormone on skin microvascular smooth
      muscle.

PMID- 15993432
TI  - Molecular epidemiology: convergence between toxicology and epidemiology.

PMID- 15993434
TI  - 5-HT1A receptor agonists modify epileptic seizures in three experimental models
      in rats.
AB  - The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1,
      0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three
      type of seizures in male Wistar rats: clonic-tonic convulsions induced by
      pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic
      seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures
      by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the
      mortality rate induced by PTZ. Indorenate increased the latency to the PTZ
      induced seizures and decreased the percentage of rats showing tonic extension and
      death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency
      of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished
      the occurrence and delayed the establishment of SE. Indorenate augmented the
      latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and
      Indorenate did not alter the expression of kindled seizures. However, Indorenate
      enhanced the refractoriness to subsequent seizures during the postictal
      depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures
      evaluated and postictal depression were fully or partially blocked by WAY100635.
      These results suggest that 5-HT1A receptor agonists modify epileptic activity
      depending on the type of seizure.

PMID- 15993433
TI  - Role of the alpha subunit in the modulation of GABA(A) receptors by anabolic
      androgenic steroids.
AB  - Neural transmission mediated by circuits expressing alpha2 subunit-containing
      gamma-aminobutyric acid type A (GABA(A)) receptors is critical for the expression
      of behaviors known to be altered by anabolic androgenic steroids (AAS). Here we
      show that micromolar concentrations of AAS, which reflect levels found in steroid
      abusers, induce positive modulation of currents from alpha2beta3 gamma2L
      recombinant receptors elicited by pulses of GABA that mimic synaptic conditions
      in a manner that is mechanistically distinct from modulation induced at
      alpha1beta3 gamma2L receptors. Specifically, at alpha2-containing receptors, the
      AAS, 17alpha-methyltestosterone (17alpha-MeT) enhanced peak current, slowed
      deactivation, diminished desensitization, and promoted entry of receptors into
      more distal states along the activation pathway. Analysis of GABA(A) receptor
      mediated synaptic currents in primary cortical neurons followed by single cell
      real-time RT-PCR demonstrated that 17alpha-MeT enhancement of synaptic currents
      is proportional to the ratio of alpha2 to alpha1 subunit mRNA. Finally, we show
      that the modulation elicited by AAS is not comparable to that produced by
      micromolar concentrations of other positive allosteric modulators at alpha2
      containing receptors. In sum, these data indicate that AAS elicit effects on
      GABA(A) receptor function that depend significantly on alpha subunit composition
      and that the mechanism of AAS modulation of GABA(A) receptors is distinct from
      that of other positive allosteric modulators.

PMID- 15993435
TI  - Neurosteroid pregnenolone sulfate inhibits stimulus-evoked EPSC via presynaptic
      inhibition of protein kinase A in rat prelimbic cortical neurons.
AB  - Pregnenolone sulfate is one of the most abundantly produced neurosteroids in the
      brain. The present paper studies the effect of pregnenolone sulfate on excitatory
      synaptic transmission in the pyramidal cells of the layer V-VI of the prelimbic
      cortex using whole-cell patch-clamp in slices. We found that pregnenolone sulfate
      inhibited stimulus-evoked excitatory postsynaptic currents (EPSC); the effect of
      pregnenolone sulfate was significant at concentration of 1 microM and increased
      with an increase in concentrations; pregnenolone sulfate had no effect on the
      amplitude and frequency of miniature excitatory spontaneous postsynaptic
      currents; pregnenolone sulfate significantly enhanced the paired-pulse
      facilitation (PPF) and inhibited dopamine and 5-HT-evoked increase in the
      frequency of spontaneous excitatory postsynaptic currents; the protein kinase A
      inhibitor H89 and Rp-cAMPS enhanced PPF and canceled the effect of pregnenolone
      sulfate on PPF; pregnenolone sulfate inhibited the protein kinase A agonist
      forskolin-evoked increase in the frequency of spontaneous excitatory postsynaptic
      currents; the G(i) protein inhibitor N-ethylmaleimide canceled the effect of
      pregnenolone sulfate on PPF. These results suggest that pregnenolone sulfate
      inhibits stimulus-evoked EPSC via presynaptic inhibition of protein kinase A in
      rat prelimbic cortical neurons.

PMID- 15993436
TI  - NMDA enhances a depolarization-activated inward current in subthalamic neurons.
AB  - Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor stimulation
      evokes Ca2+- and Na+-dependent burst firing in subthalamic nucleus (STN) neurons.
      Using whole-cell patch pipettes to record currents under voltage-clamp, we
      identified a time-dependent depolarization-activated inward current (DIC) that
      may underlie NMDA-induced burst firing in STN neurons in rat brain slices.
      Continuous superfusion with NMDA (20 microM) elicited a marked TTX-insensitive
      inward current when the membrane was depolarized to the level of -70 or -50 mV,
      from a holding potential of -100 mV. This current had a long duration, and its
      peak amplitude occurred at a test potential of -60 mV. DIC could not be evoked
      using the non-NMDA receptor agonist D,L-alpha-amino-3-hydroxy-5-methylisoxalone-4
      propionic acid (AMPA). DIC was blocked by either intracellular BAPTA or by
      removal of extracellular Ca2+, but selective blockers of T-type (mibefradil), L
      type (nifedipine) and N-type (omega-conotoxin GVIA) Ca2+ channels did not.
      Perfusing slices with a low extracellular concentration of sodium abolished the
      NMDA-induced DIC, implying that both Ca2+ and Na+ are necessary for the
      expression of DIC. Transient receptor potential (TRP) channel blockers flufenamic
      acid and SKF96365 severely reduced DIC amplitude, whereas NMDA-gated currents
      were either increased or were unchanged. These results suggest that the
      activation of NMDA receptors enhances a Ca2+-activated non-selective cation
      current that may be mediated by a member of the TRP channel family in STN
      neurons.

PMID- 15993437
TI  - Carrier-mediated release of monoamines induced by the nicotinic acetylcholine
      receptor agonist DMPP.
AB  - We have previously shown that dimethylphenylpiperazinium (DMPP) increases the
      release of noradrenaline (NA) from rat hippocampal slices via two distinct
      mechanisms: a nicotinic acetylcholine receptor (nAChR)-mediated exocytosis and a
      carrier-mediated release induced by the reversal of NA transporters. Our aim was
      to investigate whether other monoaminergic systems are also affected by the
      multiple actions of DMPP. In our experiments DMPP dose-dependently increased the
      release of dopamine (DA) and serotonin (5-HT) from rat striatal and hippocampal
      slices, respectively. The dual effect was observed, however, only in case of DA
      at a lower DMPP concentration (30 microM), where the response was partly
      inhibited by mecamylamine, TTX and Ca2+-free medium (nAChR-mediated exocytosis)
      while the other part of the response was blocked only by the DA uptake inhibitor
      nomifensine (carrier-mediated release). In contrast, the DMPP-evoked 5-HT release
      and the DA release induced by high concentration DMPP was not inhibited by
      nicotinic antagonists, TTX and Ca2+-free medium but only by selective uptake
      inhibitors. In addition, DMPP dose-dependently inhibited the [3H]DA and [3H]5-HT
      uptake in striatal and hippocampal synaptosome preparation with an IC50 of 3.18
      and 0.49 microM, respectively. Our data show that DMPP interacts with monoamine
      transporters and induces a substantial carrier-mediated release of DA and 5-HT,
      therefore caution is needed for the interpretation of data, when this drug is
      used as a nAChR agonist.

PMID- 15993438
TI  - 1-Ethyl-2-benzimidazolinone (EBIO) suppresses epileptiform activity in in vitro
      hippocampus.
AB  - Ca2+-activated K+ currents with medium (mI(AHP)) and slow (sI(AHP)) kinetics,
      that mediate the post-spike medium and slow after-hyperpolarization (AHP),
      respectively, play critical roles in regulating neuronal excitability and the
      spread of epileptiform activity and could provide new therapeutic targets for the
      management of epileptic patients. We tested if the enhancement of the mI(AHP) by
      1-ethyl-2-benzimidazolinone (EBIO) could suppress epileptiform activity in two in
      vitro models of epileptogenesis induced in CA3 hippocampal pyramidal neurons by
      superfusion with 4-AP- and kainate-Mg2+-free solutions. Both interictal- and
      ictal-like epileptiform activities were reversibly suppressed by EBIO
      concentrations between 200 microM and 1 mM. EBIO predominantly acted by a strong
      reduction of excitability via an increase (approximately 450%) of the mI(AHP),
      without changing the sI(AHP). Glutamatergic excitatory synaptic transmission was
      also diminished (approximately 50%) by 1 mM EBIO. In contrast, EBIO
      concentrations <400 microM had no effect on synaptic excitation, consistent with
      a lesser sensitivity to the drug than the mI(AHP). Apamine (100 nM), a toxin that
      specifically inhibits the mI(AHP), rapidly and reversibly antagonized the
      blocking effects of EBIO on epileptiform activity. Our results suggest that
      manipulations that enhance the mI(AHP) may prove adequate in the treatment of
      epilepsies; they also suggest that an abnormal down regulation of the mI(AHP) may
      be a key factor in the genesis of hyperexcitable states.

PMID- 15993440
TI  - Glycinergic inhibition in thalamus revealed by synaptic receptor blockade.
AB  - Using juvenile rat brain slices, we examined the possibility that strychnine
      sensitive receptors for glycine-like amino acids contributed to synaptic
      inhibition in ventrobasal thalamus, where gamma-aminobutyrate (GABA) is the
      prevalent inhibitory transmitter. Ventrobasal nuclei showed staining for
      antibodies against alpha1 and alpha2 subunits of the glycine receptor.
      Exogenously applied glycine, taurine and beta-alanine increased membrane
      conductance, effects antagonized by strychnine, indicative of functional glycine
      receptors. Using glutamate receptor antagonists, we isolated inhibitory
      postsynaptic potentials and currents (IPSPs and IPSCs) evoked by high-threshold
      stimulation of medial lemniscus. Like the responses to glycine agonists, these
      synaptic responses reversed near E(Cl). In comparative tests with GABA receptor
      antagonists, strychnine attenuated inhibition in a majority of neurons, but did
      not alter slow, GABA(B) inhibition. For complete blockade, the majority of fast
      IPSPs required co-application of strychnine with bicuculline or gabazine, GABA(A)
      receptor antagonists. Strychnine acting with an IC50 approximately = 33 nM,
      eliminated residual fast inhibition during selective GABA(A) receptor blockade
      with gabazine. The latency of onset for IPSPs was compatible with polysynaptic
      pathways or prolonged axonal propagation time. Strychnine lacked effects on
      monosynaptic, GABAergic IPSPs from zona incerta. The specific actions of
      strychnine implicated a glycine receptor contribution to fast inhibition in
      somatosensory thalamus.

PMID- 15993439
TI  - Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in
      the rat globus pallidus.
AB  - While group II metabotropic glutamate receptors (mGluRs) are known to be
      expressed in the rat globus pallidus (GP), their functions remain poorly
      understood. We used standard patch clamping technique in GP slices to determine
      the effect of group II mGluR activation on excitatory transmission in this
      region. Activation of group II mGluRs with the group-selective agonist DCG-IV or
      APDC reduced the amplitude of the evoked excitatory postsynaptic currents (EPSCs)
      and significantly increased the paired pulse ratio suggesting a presynaptic site
      of action. This was further supported by double-labeling electron microscopy data
      showing that group II mGluRs (mGluR2 and 3) immunoreactivity is localized in
      glutamatergic pre-terminal axons and terminals in the GP. Furthermore, we found
      that LY 487379, an mGluR2-specific allosteric modulator, significantly
      potentiated the inhibitory effect of DCG-IV on the excitatory transmission in the
      GP. Co-incubation with 30 microM LY 487379 increased the potency of DCG-IV about
      10-fold in the GP. We were thus able to pharmacologically isolate the mGluR2
      mediated function in the rat GP using an mGluR2-specific allosteric modulator.
      Therefore, our findings do not only shed light on the functions of group II
      mGluRs in the GP, they also illustrate the therapeutic potential of mGluR
      targeting allosteric modulators in neurological disorders such as Parkinson's
      disease.

PMID- 15993441
TI  - Agonists of peroxisome proliferator-activated receptor-gamma attenuate the Abeta
      mediated impairment of LTP in the hippocampus in vitro.
AB  - The data we present here suggest that agonists of peroxisome proliferator
      activated receptor-gamma (PPARgamma) can attenuate the effects of beta-amyloid
      peptide (Abeta). Alzheimer's disease is associated with elevated levels of Abeta,
      and enhanced expression of PPARgamma. In this study, we determined that
      application of Abeta([1-40]) could impair hippocampal post-tetanic potentiation
      (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of
      PPARgamma agonists; troglitazone, ciglitazone and 15-deoxy-delta(12,14)
      prostaglandin J2 (PGJ2) on synaptic transmission and plasticity in area CA1. Both
      ciglitazone and PGJ2 increased baseline synaptic transmission significantly,
      without altering paired-pulse facilitation. PGJ2 produced a significant reduction
      in LTP, whereas ciglitazone and troglitazone had no significant effect. In
      addition, prior application of each ligand attenuated the previously observed
      Abeta([1-40])-mediated impairment of LTP. The effect of troglitazone on the
      Abeta([1-40])-mediated impairment of LTP was not reversed by the PPARgamma
      antagonist, GW-9662. These findings demonstrate that PPARgamma agonists attenuate
      the effects of Abeta on LTP, and support the potential use of these agents to
      alleviate the symptoms of Alzheimer's disease. We also suggest that PPARgamma
      agonists may regulate expression of hippocampal LTP in vitro.

PMID- 15993442
TI  - Serotonin 5-HT2A but not 5-HT2C receptor antagonism reduces hyperlocomotor
      activity induced in dopamine-depleted rats by striatal administration of the D1
      agonist SKF 82958.
AB  - While recent work has indicated that D1 receptor agonist-induced hyperlocomotion
      in DA-depleted rats is reduced by striatal 5-HT2 receptor antagonism, the 5-HT
      receptor(s) subtypes mediating these effects are not yet known. In the present
      study, we examined the influence(s) of striatal 5-HT2A and 5-HT2C receptors on
      locomotor behavior induced by D1 agonism in neonatal DA-depleted rats. On
      postnatal day 3, male Sprague-Dawley rats (n=68) were treated with either vehicle
      or 6-hydroxydopamine (6-OHDA; 60 microg) which produced >98% DA depletion. Sixty
      days later, all rats were fitted with bilateral striatal cannulae. A subset of
      control and 6-OHDA-lesioned rats (n=20) was tested for locomotor responses to
      striatal infusion of the D1 agonist SKF 82958 (0, 0.1, 1.0, 10 microg/side). The
      remaining rats (n=48) were tested for locomotor responses to intrastriatal SKF
      82958 (2.0 microg/side) alone or in combination with the 5-HT2A- or 5-HT2C
      preferring antagonists M100907 or RS102221 (0.1 or 1.0 microg/side),
      respectively. Intrastriatal SKF 82958 dose-dependently increased measures of
      motor activity within DA-depleted rats. This hyperlocomotor activity was
      suppressed by co-infusion of M100907, but not RS102221. These results indicate
      that DA depletion strengthens striatal 5-HT2A/D1 receptor interactions and
      suggest that 5-HT2A receptor antagonists may prove useful in reducing D1-related
      movements.

PMID- 15993443
TI  - MDMA ('Ecstasy') and methamphetamine combined: order of administration influences
      hyperthermic and long-term adverse effects in female rats.
AB  - The acute and long-term dangers of 3,4-methylenedioxymethamphetamine (MDMA,
      'Ecstasy') and methamphetamine (METH) are well described individually, but their
      effect in combination is largely unknown. Here groups of female rats were given
      four MDMA or METH injections within a single session with each injection
      separated by 2h. Treatments included MDMA only, METH only, MDMA and METH in a
      cocktail (MDMA/METH), MDMA (two injections) followed by METH (two injections)
      (MDMA-->METH), or METH followed by MDMA (METH-->MDMA). Each injection involved
      4mg/kg of total drug. Drug administration occurred at a high ambient temperature
      of 28 degrees C. All treatments produced hyperactivity while the treatments where
      MDMA was administered first (MDMA, MDMA-->METH and MDMA/METH) produced
      hyperthermia. All treatments involving METH caused significant head weaving. Six
      weeks after drug treatment all groups showed reduced social interaction relative
      to controls. MDMA/METH treatment was associated with reduced swimming in the
      forced swim test. MDMA given alone caused 5-HT depletion in several brain regions
      while METH given alone caused dopamine depletion in the striatum. The three
      treatments involving MDMA and METH combinations caused significant depletion of
      serotonin, dopamine and noradrenaline in several brain regions. Interestingly,
      the MDMA-->METH treatment produced greater hippocampal and cortical 5-HT
      depletion than the METH-->MDMA treatment suggesting an effect of order. These
      results extend our recent findings of additive toxic effects when METH is
      combined with MDMA. This has potentially important implications for party drug
      users who appear to frequently use this combination.

PMID- 15993444
TI  - Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in
      parkin knock out mice.
AB  - Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces
      behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of
      motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT)
      controls. PK-KO mice have high striatal dopamine levels and increased dopamine
      metabolism in spite of low reduced tyrosine hydroxylase protein. Cinnarizine,
      which blocks dopamine receptors and increases dopamine release, further increased
      dopamine metabolism. PK-KO mice increased GSH levels as a compensatory mechanism
      against enhanced free radical production related to acceleration of dopamine
      turnover. Neuronal markers, such as beta-tubulin slightly increased in PK-KO and
      furthermore with cinnarizine. Astroglial markers were decreased in PK-KO mice,
      and this effect was potentiated by cinnarizine, suggesting abnormal glia in these
      animals. Microglia was hyperactivated in PK-KO midbrain, suggesting inflammation
      in these animals. Proapoptotic proteins were increased by cinnarizine and, to a
      lesser extent, in PK-KO mice. Our data indicate that mutation of parkin is a risk
      factor for drug-induced parkinsonism.

PMID- 15993445
TI  - Dissection of peripheral and central endogenous opioid modulation of systemic
      interleukin-1beta responses using c-fos expression in the rat brain.
AB  - In opiate addicts or patients receiving morphine treatment, it has been reported
      that the immune system is often compromised. The mechanisms responsible for the
      adverse effects of opioids on responses to infection are not clear but it is
      possible that central and/or peripheral opioid receptors may be important. We
      have utilised an experimental immune challenge model in rats, the systemic
      administration of the human pro-inflammatory cytokine interleukin-1beta (IL
      1beta) to study the effects of selectively blocking peripheral opioid receptors
      only (using naloxone methiodide) or after blocking both central and peripheral
      opioid receptors (using naloxone). Pre-treatment with naloxone methiodide
      decreased (15%) IL-1beta-induced Fos-immunoreactivity (Fos-IR) in medial
      parvocellular paraventricular nucleus (mPVN) corticotropin-releasing hormone
      (CRH) neurons but increased responses in the ventrolateral medulla (VLM) C1 (65%)
      and nucleus tractus solitarius (NTS) A2 (110%) catecholamine cell groups and area
      postrema (136%). However no effect of blocking peripheral opioid receptors was
      detected in the central nucleus of the amygdala (CeA) or dorsal bed nucleus of
      the stria terminalis (BNST). We next determined the effect of blocking both
      central and peripheral opioid receptors with naloxone and, when compared to the
      naloxone methiodide pre-treated group, a further 60% decrease in Fos-IR mPVN CRH
      neurons induced by IL-1beta was detected, which was attributed to block of
      central opioid receptors. Similar comparisons also detected decreases in Fos-IR
      neurons induced by IL-1beta in the VLM A1, VLM C1 and NTS A2 catecholamine cell
      groups, area postrema, and parabrachial nucleus. In contrast, pre-treatment with
      naloxone increased Fos-IR neurons in CeA (98%) and dorsal BNST (72%). These
      results provide novel evidence that endogenous opioids can influence central
      neural responses to systemic IL-1beta and also suggest that the differential
      patterns of activation may arise because of actions at central and/or peripheral
      opioid receptors that might be important in regulating behavioural, hypothalamic
      pituitary-adrenal axis and sympathetic nervous system responses during an immune
      challenge.

PMID- 15993446
TI  - Ethanol differentially affects ATP-gated P2X(3) and P2X(4) receptor subtypes
      expressed in Xenopus oocytes.
AB  - P2X receptors are cation-selective, ligand-gated ion channels activated by
      synaptically released, extracellular adenosine 5'-triphosphate (ATP). ATP-gated
      currents are inhibited by ethanol when tested in dorsal root ganglion and CA1
      neurons. Recently, we reported differences in sensitivity to ethanol inhibition
      between homomeric P2X(2) and P2X(4) receptors expressed in Xenopus oocytes, which
      suggested that subunit composition of native P2X receptors determines their
      ethanol sensitivity. The present study extended the investigation to P2X(3)
      receptors. The effects of ethanol and zinc ions (Zn(2+)) were tested on homomeric
      P2X(3) and P2X(4) receptors expressed in Xenopus oocytes using two-electrode
      voltage clamp. Ethanol potentiated ATP-gated P2X(3) receptor currents in a
      concentration dependent manner. In contrast, ethanol inhibited P2X(4) receptor
      function. Ethanol did not directly alter receptor function, nor did it alter the
      Hill coefficient or maximal ATP response (E(max)) in either P2X(3) or P2X(4)
      receptors. Ethanol increased the maximal response to Zn(2+) ATP-gated currents in
      P2X3 receptors which suggests that ethanol and Zn(2+) act on different sites. The
      differences in ethanol response of P2X(3) and P2X(4) receptors set the stage for
      future investigations that will use chimeric P2X receptors or other molecular
      manipulations of P2X structure to investigate the molecular sites and mechanisms
      of action of ethanol.

PMID- 15993447
TI  - Regionally selective and dose-dependent effects of the ampakines Org 26576 and
      Org 24448 on local cerebral glucose utilisation in the mouse as assessed by 14C-2
      deoxyglucose autoradiography.
AB  - AMPA receptor potentiating drugs (e.g. ampakines) enhance glutamatergic
      neurotransmission, and may have potential therapeutic consequences in CNS
      disorders. The neuroanatomical basis of action for these compounds is at present
      unclear. This study aimed to identify the effects of two novel ampakines, Org
      26576 and Org 24448, on local cerebral glucose use (LCGU) in the mouse. C57BL/6J
      mice received Org 26576 (0.1, 1, 10 mg/kg i.p.) or Org 24448 (3, 10, 30 mg/kg
      i.p.) or vehicle and LCGU was assessed using 14C-2-deoxyglucose autoradiography.
      Both compounds produced dose-dependent increases in LCGU with specific regional
      activation at low doses. Org 26576 (1 mg/kg) produced significant increases in 9
      of the 43 areas examined, including the anteroventral and laterodorsal thalamus,
      cingulate cortex, dentate gyrus and CA3 subfield of the hippocampus. Org 24448 (3
      mg/kg) produced significant increases in LCGU in 4 of the 43 regions examined,
      including the dorsal raphe nucleus, medial lateral habenula, CA1 subfield of the
      hippocampus and median forebrain bundle. Furthermore, the increases in LCGU
      observed with both Org 26576 (10 mg/kg) and Org 24448 (10 mg/kg) were blocked by
      pre-treatment with the AMPA receptor antagonist NBQX (10 mg/kg). These data
      demonstrate that both Org 26576 and Org 24448 produce dose-dependent AMPA
      receptor mediated increases in LCGU and provide an anatomical basis suggestive
      that these drugs may be of use in the treatment of conditions such as depression
      or schizophrenia.

PMID- 15993448
TI  - Fluoxetine inhibits ATP-induced [Ca(2+)](i) increase in PC12 cells by inhibiting
      both extracellular Ca(2+) influx and Ca(2+) release from intracellular stores.
AB  - Fluoxetine, a widely used antidepressant, has additional effects, including the
      blocking of voltage-gated ion channels. We examined whether fluoxetine affects
      ATP-induced calcium signaling in PC12 cells using fura-2-based digital calcium
      imaging, an assay for [3H]-inositol phosphates (IPs) and whole-cell patch
      clamping. Treatment with ATP (100 microM) for 2 min induced increases in
      intracellular free Ca(2+) concentrations ([Ca(2+)](i)). Treatment with fluoxetine
      (100 nM to 30 microM) for 5 min inhibited the ATP-induced [Ca(2+)](i) increases
      in a concentration-dependent manner (IC(50) = 1.85 microM). Treatment with
      fluoxetine (1.85 microM) for 5 min significantly inhibited the ATP-induced
      responses following the removal of extracellular Ca(2+) or depletion of
      intracellular Ca(2+) stores. Whereas treatment for 10 min with nimodipine (1
      microM) significantly inhibited the ATP-induced [Ca(2+)](i) increase, treatment
      with fluoxetine further inhibited the ATP-induced response. Treatment with
      fluoxetine significantly inhibited [Ca(2+)](i) increases induced by 50 mM K(+).
      In addition, treatment with fluoxetine markedly inhibited ATP-induced inward
      currents in a concentration-dependent manner. However, treatment with fluoxetine
      did not inhibit ATP-induced [3H]-IPs formation. Therefore, we conclude that
      fluoxetine inhibits ATP-induced [Ca(2+)](i) increases in PC12 cells by inhibiting
      both the influx of extracellular Ca(2+) and the release of Ca(2+) from
      intracellular stores without affecting IPs formation.

PMID- 15993449
TI  - Recollection and familiarity in negative schizophrenia.
AB  - Using the "remember-know" procedure to assess recognition memory, previous
      studies yielded evidence of impaired recollection but intact familiarity in
      schizophrenia patients. However, so far, the recognition memory performance of
      schizophrenia patients has not yet been analysed using the dual-process signal
      detection model (DPSD) by Yonelinas [Yonelinas, A. P. (2001). Components of
      episodic memory: The contribution of recollection and familiarity. Philosophical
      Transactions of Royal Society of London. Series B: Biological Sciences,
      356(1413), 1363-1374], which accurately accounts for response and memory bias.
      Also, clinical symptoms have not yet been taken into account. Based on findings
      from neuropsychological and neurobiological research we hypothesized that high
      negative symptoms might be associated with a profile of impaired recollection and
      spared familiarity. The recognition memory performance of 22 schizophrenia
      patients scoring higher or lower on the negative symptoms subscale of the
      Positive and Negative Syndrome Scale (PANSS) was assessed by means of a word list
      discrimination task. Following the rationale of the dual-process signal detection
      model, estimates of recollection and familiarity were derived. The recollection
      estimate, derived by the DPSD model, was lower in patients with more severe
      negative symptomatology compared with both the patients with lower negative
      symptoms scores and healthy individuals. Familiarity was not affected if IQ was
      partialled out. Furthermore, the results yielded increased false alarm rates in
      patients with negative schizophrenia. The findings confirm an association of
      negative symptoms and recollection impairment in schizophrenia.

PMID- 15993450
TI  - Imported concomitant coccidioidomycosis and histoplasmosis in an HIV-infected
      Colombian migrant in France.
AB  - We report the case of a Colombian immunosuppressed migrant hospitalized in France
      with fever, dry cough and altered general health. Results of blood culture and
      bronchoalveolar lavage led to the diagnosis of the first reported case of
      concomitant disseminated histoplasmosis and pulmonary coccidioidomycosis in an
      HIV-infected patient.

PMID- 15993451
TI  - T cell immune responses to mycobacterial antigens in Brazilian tuberculosis
      patients and controls.
AB  - Production of IFN-gamma guarantees helpful T cell-mediated immunity against
      Mycobacterium tuberculosis infection. We have evaluated the in vitro immune
      responses to M. tuberculosis antigens using IFN-gamma production among 43
      Brazilian tuberculosis (TB) patients prior to and after specific treatment, and
      18 community controls. Peripheral blood mononuclear cells (PBMC) were cultivated
      in the presence either of purified protein derivative, ferritin, 10 kDa, 38 kDa,
      MPT59, Ag85A or Ag85B. Also, the two M. tuberculosis and M. bovis heat-shock
      proteins (hsp) 65 and 70 kDa were compared, and 5 day supernatants were harvested
      for cytokine detection by ELISA. The results showed that the overall profile of
      primary PBMC in response to most M. tuberculosis antigens was well correlated,
      since high IFN-gamma levels were induced by Ag85A, Ag85B, 38 kDa, ferritin and 10
      kDa, as well as M. tuberculosis hsp65 in TB patients. In addition, analysis was
      carried out of the in vitro expression of activation molecules on lymphocytes, as
      CD25 and CD69 expression assessed in 17 TB patients showed induction on CD4+ T
      cells by Ag85B. Overall, significantly low responses were found in untreated, in
      comparison with the treated TB patients. Furthermore, internal community but not
      healthy control individuals have higher immune responses than do TB patients.

PMID- 15993452
TI  - An integrated framework for health and ecological risk assessment.
AB  - The World Health Organization's (WHO's) International Program for Chemical Safety
      has developed a framework for performing risk assessments that integrate the
      assessment of risks to human health and risks to nonhuman organisms and
      ecosystems. The WHO's framework recognizes that stakeholders and risk managers
      have their own processes that are parallel to the scientific process of risk
      assessment and may interact with the risk assessment at various points, depending
      on the context. Integration of health and ecology provides consistent expressions
      of assessment results, incorporates the interdependence of humans and the
      environment, uses sentinel organisms, and improves the efficiency and quality of
      assessments relative to independent human health and ecological risk assessments.
      The advantage of the framework to toxicologists lies in the opportunity to use
      understanding of toxicokinetics and toxicodynamics to inform the integrated
      assessment of all exposed species.

PMID- 15993453
TI  - The human genome project and novel aspects of cytochrome P450 research.
AB  - Currently, 57 active cytochrome P450 (CYP) genes and 58 pseudogenes are known to
      be present in the human genome. Among the genes discovered by initiatives in the
      human genome project are CYP2R1, CYP2W1, CYP2S1, CYP2U1 and CYP3A43, the latter
      apparently encoding a pseudoenzyme. The function, polymorphism and regulation of
      these genes are still to be discovered to a great extent. The polymorphism of
      drug metabolizing CYPs is extensive and influences the outcome of drug therapy
      causing lack of response or adverse drug reactions. The basis for the differences
      in the global distribution of the polymorphic variants is inactivating gene
      mutations and subsequent genetic drift. However, polymorphic alleles carrying
      multiple active gene copies also exist and are suggested in case of CYP2D6 to be
      caused by positive selection due to development of alkaloid resistance in North
      East Africa about 10,000-5000 BC. The knowledge about the CYP genes and their
      polymorphisms is of fundamental importance for effective drug therapy and for
      drug development as well as for understanding metabolic activation of carcinogens
      and other xenobiotics. Here, a short review of the current knowledge is given.

PMID- 15993454
TI  - Current and emerging challenges in toxicopathology: carcinogenic threshold of
      phenobarbital and proof of arsenic carcinogenicity using rat medium-term
      bioassays for carcinogens.
AB  - For the last 25 years, Prof. Nobuyuki Ito and his laboratory have focused on the
      development of liver medium-term bioassay system for detection of carcinogens in
      F344 rats utilizing glutathione S-transferase placental form (GST-P)-positive
      foci as an end point marker. In this presentation, the outline and samples of
      medium-term bioassay systems were described. Furthermore, our data demonstrated
      the presence of a threshold for the non-genotoxic carcinogen, phenobarbital (PB),
      and the lack of linearity in the low-dose area of the dose-response curve,
      providing evidence for hormesis. In addition, the establishment and applications
      of multiorgan carcinogenicity bioassay (DMBDD model), used for the examination of
      the carcinogenicity of genotoxic and non-genotoxic chemicals, are discussed.
      Dimethylarsinic acid, one of organic arsenics, was found to be carcinogenic in
      rat bladder using DMBDD model and carcinogenicity test.

PMID- 15993455
TI  - The influence of high iron diet on rat lung manganese absorption.
AB  - Individuals chronically exposed to manganese are at high risk for neurotoxic
      effects of this metal. A primary route of exposure is through respiration,
      although little is known about pulmonary uptake of metals or factors that modify
      this process. High dietary iron levels inversely affect intestinal uptake of
      manganese, and a major goal of this study was to determine if dietary iron
      loading could increase lung non-heme iron levels and alter manganese absorption.
      Rats were fed a high iron (1% carbonyl iron) or control diet for 4 weeks. Lung
      non-heme iron levels increased approximately 2-fold in rats fed the high iron
      diet. To determine if iron-loading affected manganese uptake, 54Mn was
      administered by intratracheal (it) instillation or intravenous (iv) injection for
      pharmacokinetic studies. 54Mn absorption from the lungs to the blood was lower in
      it-instilled rats fed the 1% carbonyl iron diet. Pharmacokinetics of iv-injected
      54Mn revealed that the isotope was cleared more rapidly from the blood of iron
      loaded rats. In situ analysis of divalent metal transporter-1 (DMT1) expression
      in lung detected mRNA in airway epithelium and bronchus-associated lymphatic
      tissue (BALT). Staining of the latter was significantly reduced in rats fed the
      high iron diet. In situ analysis of transferrin receptor (TfR) mRNA showed
      staining in BALT alone. These data demonstrate that manganese absorption from the
      lungs to the blood can be modified by iron status and the route of
      administration.

PMID- 15993456
TI  - Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV
      1 Vif.
AB  - While the human antiretroviral defense factors APOBEC3F and APOBEC3G are potent
      inhibitors of the replication of HIV-1 mutants lacking a functional vif gene, the
      Vif protein expressed by wild-type HIV-1 blocks the function of both host cell
      proteins. Here, we report that a third human protein, APOBEC3B, is able to
      suppress the infectivity of both Vif-deficient and wild-type HIV-1 with equal
      efficiency. APOBEC3B, which shows approximately 58% sequence identity to both
      APOBEC3F and APOBEC3G, shares the ability of these other human proteins to bind
      the nucleocapsid domain of HIV-1 Gag specifically and to thereby package into
      progeny virion particles. However, APOBEC3B differs from APOBEC3F and APOBEC3G in
      that it is unable to bind to HIV-1 Vif in co-expressing cells and is therefore
      efficiently packaged into HIV-1 virions regardless of Vif expression.
      Unfortunately, APOBEC3B also differs from APOBEC3F and APOBEC3G in that it is not
      normally expressed in the lymphoid cells that serve as targets for HIV-1
      infection. These studies therefore raise the possibility that activation of the
      endogenous APOBEC3B gene in primary human lymphoid cells could form a novel and
      effective strategy for inhibition of HIV-1 replication in vivo.

PMID- 15993457
TI  - Computational neurobiology of the flash-lag effect.
AB  - In the flash-lag effect (FLE) a moving object is perceived ahead of a stationary
      stimulus flashed in spatial alignment. Several explanations have been proposed to
      account for the FLE and its dependence on a variety of psychophysical attributes.
      Here, we show that a simple feed-forward network reproduces the standard FLE and
      several related manifestations, such as its modulation by stimulus luminance,
      trajectory, priming, and spatial predictability. A minimal set of elements, based
      on plausible neuronal mechanisms, yields a unified account of these visual
      illusions and possibly other perceptual phenomena.

PMID- 15993458
TI  - Mechanical properties and functional importance of pulley bands or 'faisseaux
      tendineux'.
AB  - INTRODUCTION: Connective tissue bands connect the horizontal rectus muscles at
      the level of the posterior pole to the orbital wall. These bands, referred to as
      pulley bands or faisseaux tendineux, purportedly act like springs to keep the
      rectus muscle bellies in place during eye movement out of the plane of the
      muscle. We examined the mechanical properties of these bands in human specimens
      obtained during surgery. In addition, we examined eye motility and stability of
      rectus muscles in a patient who had no functional pulley bands. METHODS:
      Exenterations were carried out on two patients with sebaceous gland carcinoma.
      Pulley bands were identified and force-elongation behavior was examined with a
      forceps and a force gauge. Stability of rectus muscles was examined in a patient
      with severe Crouzon's syndrome by orbital CT scans and during surgery under
      local, eye drop, anesthesia. RESULTS: The pulley bands showed leash-like
      mechanical behavior: they were slack over approximately 10mm and became taut when
      stretched further. In the patient with Crouzon's syndrome, both CT and
      observation of the muscle during surgery showed little sideways displacement of
      the muscle bellies in eye movement out of the plane of the muscle, despite the
      lack of functional pulley bands. DISCUSSION: The leash-like mechanical behavior
      of the pulley bands seems unsuited for stabilization of the muscle bellies. The
      patient with Crouzon's syndrome had relatively good eye motility and stable
      rectus muscle paths despite the lack of functional pulley bands.

PMID- 15993459
TI  - Attention and feature integration in the feature inheritance effect.
AB  - Features of neighboring elements are not processed independently. Often, it is
      assumed that nearby features are integrated by a (pre-attentive) pooling
      mechanism. Here, we show that in the feature inheritance effect some features are
      integrated across space whereas others are not. This result may be partly
      explained by a very focused spatial attention. Our findings challenge models
      based on a simple pooling mechanism.

PMID- 15993460
TI  - Studies of hexavalent chromium attenuation in redox variable soils obtained from
      a sandy to sub-wetland groundwater environment.
AB  - Laboratory experiments were conducted to characterize and quantify the capacity
      and kinetics of the combined effects of natural attenuation processes, such as
      adsorption, reduction, and precipitation, for hexavalent chromium [Cr(VI)] in a
      variable geochemical (i.e. fraction of organic carbon [foc], redox) environment
      of glaciated soils. Equilibrium attenuation terms: linear sorption (K(d)),
      estimated capacity, and non-linear Langmuir (K(L), Q) sorption parameters; varied
      over several orders of magnitude. The pseudo-first-order rate of disappearance of
      Cr(VI) from aqueous:soil slurries ranged from approximately 10(-5) to
      approximately 10(-1)/min. An operationally defined kinetic attenuation term,
      attenuation capacity (AC), describing the quantity of Cr(VI) disappearing from
      the slurries, ranged from 1.1 to approximately 12 microg Cr(VI)/g soil/7 days.
      The linear K(d)'s and estimated attenuation capacities were indirectly and
      directly related to increasing soil pH and foc, respectively. The AC values
      decreased and increased as a function of increasing soil pH and foc,
      respectively. The parameters determined in this work were used to evaluate the
      kinetics, capacity, and stability of chromium attenuation in the sub-wetland
      saturated soils in Hellerich (2004. A field, laboratory, and modeling study of
      natural attenuation processes affecting the fate and transport of hexavalent
      chromium in a redox variable groundwater environment. Ph.D. Dissertation,
      Department of Civil and Environmental Engineering, University of Connecticut
      Storrs) using a statistical simulation framework.

PMID- 15993461
TI  - In situ identification and characterization of the microbial community structure
      of full-scale enhanced biological phosphorous removal plants in Japan.
AB  - Fluorescent in situ hybridization (FISH) and polyphosphate (polyP) staining
      methods were used to characterize the microbial community structure of 13
      activated sludge samples taken from nine different Japanese wastewater treatment
      plants with and without enhanced biological phosphorous removal (EBPR)
      activities. FISH with published rRNA-targeted oligonucleotide probes for
      important bacterial groups involving in the EBPR process revealed that
      Rhodocyclus-related polyphosphate accumulating organisms (PAOs) and glycogen
      accumulating organisms from a gammaproteobacterial lineage GB were the
      predominant populations detected, representing 4-18% and 10-31% of EUBmix-stained
      cells, respectively, in those samples. However, a considerable proportion of
      Rhodocyclus-related PAO cells were observed with no polyP granules accumulated
      based on polyP staining. This was further supported by a poor correlation between
      Rhodocyclus-related PAO population and sludge total phosphorous (TP) contents. In
      contrast, high correlations between polyP-stained cells and sludge TP contents
      were observed. In particular, among those polyP-stained cells in samples
      Ariake_A2O and Nakano_AO, more than 85% of them could not be targeted by probe
      PAOmix. These non-Rhodocyclus-related PAOs included populations from other
      bacterial divisions and members of the Betaproteobacteria other than those in
      Rhodocyclus-related group.

PMID- 15993462
TI  - Purification of chromium(VI) finishing wastewaters using calcined and uncalcined
      Mg-Al-CO3-hydrotalcite.
AB  - The applicability of calcined and uncalcined hydrotalcite for the purification of
      industrial effluents has been studied using chromium finishing wastewaters. Using
      a batch method, the influence of the initial concentration of chromium (10
      450mg/l), hydrotalcite (HT) dose (0.5-5g/l) and time (0.5-72h) has been
      evaluated. The process could be described by the Langmuir model and gave a
      maximum removal of chromium of 16.3mg Cr(VI)/g on uncalcined HT and 128mg
      Cr(VI)/g on calcined hydrotalcite (C-HT). Removal using the calcined product
      provided an effective system to treat chromium finishing wastewaters with the
      most stringent discharge limit for such industrial streams being achieved with
      between two and four consecutive removal cycles on C-HT at a dose of 2g/l.

PMID- 15993463
TI  - The effects of combined ozonation and filtration on disinfection by-product
      formation.
AB  - The effects of combined ozonation and membrane filtration on the removal of the
      natural organic matter (NOM) and the formation of disinfection by-products (DBPs)
      were investigated. Ozonation/filtration resulted in a reduction of up to 50% in
      the dissolved organic carbon (DOC) concentration. Furthermore, humic substances
      were converted to non-humic substances, with changes in the humic and non-humic
      substance concentrations of up to -50% and +20%, respectively.
      Ozonation/filtration resulted in the formation of partially oxidized compounds
      from NOM that were less reactive with chlorine, decreasing the concentration of
      simulated distribution system total trihalomethanes (SDS TTHMs) and simulated
      distribution system halo acetic acids (SDS HAAs) by up to 80% and 65%,
      respectively. Reducing the molecular weight cut-off (MWCO) of the membranes
      resulted in reductions in the concentrations of SDS TTHMs and SDS HAAs. Using a
      membrane with a 5 kD MWCO, the minimum gaseous ozone concentration required to
      bring about effective NOM degradation and meet regulatory requirements for
      chlorinated DBPs was 2.5 g/m(3).

PMID- 15993464
TI  - Effect of polyelectrolyte conditioning on the enhanced dewatering of activated
      sludge by application of an electric field during the expression phase.
AB  - Activated sludge is known to be poorly dewaterable due to its high surface charge
      density and the extreme solids compressibility, even after polyelectrolyte
      conditioning. The application of an electric field during pressure dewatering
      (PDW) of sludge can enhance the dewaterability by the electroosmosis effect. A
      comparative study was conducted to investigate the additional effect of an
      electric field, applied during the expression phase, on the dewatering course of
      polyelectrolyte conditioned sludge, compared to mere PDW. It was found that the
      application of an electric field markedly improved the dewatering kinetics for
      all sludge samples, regardless of the conditioning treatment. Although the
      conditioning polyelectrolyte characteristics and dose had a major effect on the
      PDW of sludge, the conditioning history did not have a significant effect on the
      electroosmotic water transport efficiency during the sludge expression phase. By
      means of on-line streaming potential measurements and fractionated filtrate
      electrophoretic mobility measurements, it could be demonstrated that even at high
      polyelectrolyte doses, leading to positively charged sludge flocs, negative
      surface charges were still present inside the sludge matrix. During the
      expression of the sludge cake, when liquid is forced to move through the floc
      inside pores, these negative surface charges hampered PDW, but enhanced
      electroosmotic dewatering. Electroosmosis is therefore an appropriate technique
      to remove the water fraction that is associated with these negative surface
      charges.

PMID- 15993465
TI  - A critical comparison of systematic calibration protocols for activated sludge
      models: a SWOT analysis.
AB  - Modelling activated sludge systems has gained an increasing momentum after the
      introduction of activated sludge models (ASMs) in 1987. Application of dynamic
      models for full-scale systems requires essentially a calibration of the chosen
      ASM to the case under study. Numerous full-scale model applications have been
      performed so far which were mostly based on ad hoc approaches and expert
      knowledge. Further, each modelling study has followed a different calibration
      approach: e.g. different influent wastewater characterization methods, different
      kinetic parameter estimation methods, different selection of parameters to be
      calibrated, different priorities within the calibration steps, etc. In short,
      there was no standard approach in performing the calibration study, which makes
      it difficult, if not impossible, to (1) compare different calibrations of ASMs
      with each other and (2) perform internal quality checks for each calibration
      study. To address these concerns, systematic calibration protocols have recently
      been proposed to bring guidance to the modeling of activated sludge systems and
      in particular to the calibration of full-scale models. In this contribution four
      existing calibration approaches (BIOMATH, HSG, STOWA and WERF) will be critically
      discussed using a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis.
      It will also be assessed in what way these approaches can be further developed in
      view of further improving the quality of ASM calibration. In this respect, the
      potential of automating some steps of the calibration procedure by use of
      mathematical algorithms is highlighted.

PMID- 15993466
TI  - HCHs and DDTs in sediment-dwelling animals from the Yangtze Estuary, China.
AB  - HCHs and DDTs in sediment-dwelling animals including mollusks and crabs from the
      Yangtze Estuary were determined by GC-ECD. Levels of t-HCH were in the range of
      1.2-5.5 ng g(-1) and averaged 3.5 ng g(-1) in mollusks, while t-DDT
      concentrations ranged from 26.0 to 68.8 ng g(-1), with a mean of 34.5 ng g(-1).
      In crabs t-HCH concentrations varied from 2.0 to 25.7 ng g(-1) and averaged 13.8
      ng g(-1), whereas the concentrations of t-DDT were in the range of 1.5-24.8 ng g(
      1) with a mean value of 5.9 ng g(-1). The HCHs and DDTs levels depend on
      geographical position and sources, showing the high levels at fresh water area in
      the estuary, such as XP, CM and LHK sites, and lower at brackish water area, such
      as FX site, and little difference between species. Results also indicate there
      was no significant relationship between t-HCH (t-DDT) concentrations and lipid
      contents both in mollusks and crabs because of non-equilibrium state under a
      specific estuarine dynamics; smaller individuals accumulated more HCHs and DDTs
      than larger individuals of mollusks at LHK site, showing different uptake rate
      for these pesticides; moreover, HCHs and DDTs levels were lower in female crab
      bodies than male crab bodies suggesting that the release of spawning. BSAFs
      (Biota- Sediment Accumulation Factors) from sediment-dwelling animals for HCHs
      and DDTs show a significant "one high with two low" and "one low with two high"
      effect in the Yangtze Estuary.

PMID- 15993467
TI  - Intramolecular distribution of stable nitrogen and oxygen isotopes of nitrous
      oxide emitted during coal combustion.
AB  - The intramolecular distribution of stable isotopes in nitrous oxide that is
      emitted during coal combustion was analyzed using an isotopic ratio mass
      spectrometer equipped with a modified ion collector system (IRMS). The coal was
      combusted in a test furnace fitted with a single burner and the flue gases were
      collected at the furnace exit following removal of SO(x), NO(x), and H2O in order
      to avoid the formation of artifact nitrous oxide. The nitrous oxide in the flue
      gases proved to be enriched in 15N relative to the fuel coal. In air-staged
      combustion experiments, the staged air ratio was controlled over a range of 0
      (unstaged combustion), 20%, and 30%. As the staged air ratio increased, the
      delta15N and delta18O of the nitrous oxide in the flue gases became depleted. The
      central nitrogen of the nitrous oxide molecule, N(alpha), was enriched in 15N
      relative to that occupying the end position of the molecule, N(beta), but this
      preference, expressed as delta15N(alpha)-delta15N(beta), decreased with the
      increase in the staged air ratio. Thermal decomposition and hydrogen reduction
      experiments carried out using a tube reactor allowed qualitative estimates of the
      kinetic isotope effects that occurred during the decomposition of the nitrous
      oxide and quantitative estimates of the extent to which the nitrous oxide had
      decomposed. The site preference of nitrous oxide increased with the extent of the
      decomposition reactions. Assuming that no site preference exists in nitrous oxide
      before decomposition, the behavior of nitrous oxide in the test combustion
      furnace was analyzed using the Rayleigh equation based on a single distillation
      model. As a result, the extent of decomposition of nitrous oxide was estimated as
      0.24-0.26 during the decomposition reaction governed by the thermal decomposition
      and as 0.35-0.38 during the decomposition reaction governed by the hydrogen
      reduction in staged combustion. The intramolecular distribution of nitrous oxide
      can be a valuable parameter to estimate the extent of decomposition reaction and
      to understand the reaction pathway of nitrous oxide at the high temperature.

PMID- 15993468
TI  - Quantitative relationships between molecular structures, environmental
      temperatures and solid vapor pressures of PCDD/Fs.
AB  - Based on quantum chemical and topological descriptors, temperature-dependent
      predictive models for solid vapor pressure (PS) of PCDD/Fs were developed. The
      inclusion of the two topological descriptors, Kier symmetry index (S0K) and Kier
      flexibility index (PHI), as predictor variables, improved the statistical
      significance of models. Thus the entropic factors described by the two
      topological descriptors play a role in influencing the PS values. The cumulative
      variance of the dependent variable explained by the PLS components and determined
      by cross-validation (Qcum2), for the final model, is 0.972, indicating that the
      model has good predictive ability and robustness, and could be used to estimate
      PS values of PCDD/Fs at different temperatures. The main factors governing log PS
      values of PCDD/Fs, from important to less important, are temperature,
      intermolecular dispersive interactions, entropic factor, and intermolecular
      dipole-dipole and dipole-induced dipole interactions.

PMID- 15993469
TI  - Cadmium accumulation and its influence on lipid peroxidation and antioxidative
      system in an aquatic plant, Bacopa monnieri L.
AB  - Bacopa monnieri L. plants exposed to 10, 50, 100 and 200 microM cadmium (Cd) for
      48, 96 and 144 h were analysed with reference to the accumulation of metal and
      its influence on various enzymatic and non-enzymatic antioxidants, thiobarbituric
      acid reactive substances (TBARS), photosynthetic pigments and protein content.
      The accumulation of Cd was found to be increased in a concentration and duration
      dependent manner with more Cd being accumulated in the root. TBARS content of the
      treated roots and leaves increased with increase in Cd concentration and exposure
      periods, indicating the occurrence of oxidative stress. Induction in the
      activities of superoxide dismutase (SOD), ascorbate peroxidase (APX) and guiacol
      peroxidase (GPX) was recorded in metal treated roots and leaves of B. monnieri.
      In contrast, a significant reduction in catalase activity in Cd treated B.
      monnieri was observed. An increase was also noted in the levels of cysteine and
      non-protein thiol contents of the roots of B. monnieri followed by a decline.
      However, in leaves, cysteine and non-protein thiol contents were found to be
      enhanced at all the Cd concentrations and exposure periods. A significant
      reduction in the level of ascorbic acid was observed in a concentration and
      duration dependent manner. The total chlorophyll and protein content of B.
      monnieri decreased with increase in Cd concentration at all the exposure periods.
      Results suggest that toxic concentrations of Cd caused oxidative damage as
      evidenced by increased lipid peroxidation and decreased chlorophyll and protein
      contents. However, B. monnieri is able to combat metal induced oxidative injury
      involving a mechanism of activation of various enzymatic and non-enzymatic
      antioxidants.

PMID- 15993470
TI  - The case is unchanged and remains robust: Australopithecus afarensis exhibits
      only moderate skeletal dimorphism. A reply to Plavcan et al. (2005).

PMID- 15993471
TI  - EPR examination of Zn2+ and Cu2+ binding by pigmented soil fungi Cladosporium
      cladosporioides.
AB  - The purpose of this study was to examine the usefulness of electron paramagnetic
      resonance spectroscopy (EPR) to estimate zinc and copper ions biosorption from
      the environment by pigmented soil fungi Cladosporium cladosporioides. The
      existence of a low amount of pheomelanin, besides eumelanin, in C.
      cladosporioides samples was proved by the analysis of shape of their EPR spectra.
      Concentration of o-semiquinone free radicals in crude mycelium was 2.4x10(17)
      spin/g. Changes in free radicals system of C. cladosporioides cultured in the
      presence of Zn2+ and Cu2+ were analysed. Both magnetic and chemical interactions
      of zinc and copper ions with free radicals in C. cladosporioides melanin were
      found. Magnetically interacting diamagnetic Zn2+ ions increased the concentration
      of o-semiquinone free radicals in melanin existing in C. cladosporioides
      mycelium, whereas paramagnetic Cu2+ ions decreased this concentration. Chemical
      interactions of Zn2+ and Cu2+ ions decreased the free radical concentrations in
      C. cladosporioides melanin. Homogeneously distributed free radicals in C.
      cladosporioides melanin rise its activity in biosorption processes.

PMID- 15993472
TI  - Enhancing spatial estimates of metal pollutants in raw wastewater irrigated
      fields using a topsoil organic carbon map predicted from aerial photography.
AB  - Various approaches have been used to estimate metal pollutant element (TE)
      contents at unsampled locations in a 15-ha contaminated site located in the plain
      of Pierrelaye-Bessancourt (about 24 km Northwest of Paris). 87 samples of soil
      plough layer were randomly sampled at each mesh of a regular square grid over the
      whole study area and the total contents of Cd, Cr, Cu, Ni, Pb, and Zn were
      measured. A first set of 50 measurements, randomly selected from the 87 samples,
      was used for the prediction and another set of 37 measurements was kept for the
      validation. Topsoil organic carbon contents (SOC) were measured at 75 sites with
      50 measurements sharing the same locations as TE. An aerial photography of the
      study area showing bare soils was selected for relating brightness intensities
      and SOC. Mapping procedures used were ordinary kriging (OK), cokriging (COK),
      collocated cokriging (CC), and kriging with external drift (KED). SOC maps used
      as exhaustively sampled information in KED and CC of TE were obtained by KED and
      CC procedures, respectively, accounting for 75 SOC measurements and the
      brightness intensities of numerical counts provided by the visible bands of the
      aerial photograph bare soils. Consequently, for each TE, four maps were
      generated: two maps resulting from KED and CC procedures (KED-SOC75P, CC-SOC75P),
      another one provided by standard cokriging (COK-TE50SOC75) accounting for TE
      prediction set plus 75 SOC measurements, and the last one corresponding to that
      estimated by ordinary kriging from only prediction set measurements (OK50). Three
      indices: (1) the mean prediction error (ME) and the mean absolute prediction
      error (|ME|); (2) the root mean square error (RMSE); and (3) the relative
      improvement (RI) of accuracy, as well as residuals analysis, were computed from
      the validation set (observed data) and predicted values. On the 37 test data, the
      results showed that the more accurate predictions were systematically those
      obtained by kriging accounting for SOC map predicted by KED from 75 SOC
      measurements and brightness values of the aerial photo (KED-SOC75P) followed
      closely by CC-SOC75P procedure, except for Cu and Zn where CC-SOC75P appeared to
      be slightly more accurate than KED-SOC75P. In regard to the RI of accuracy
      between prediction methods, the results confirmed once for all the benefit of
      accounting for SOC data set plus the exhaustively sampled information provided by
      the aerial photography regardless of the considered TE. Nevertheless, for Cd, Pb,
      and Zn, the RI of accuracy was less than 20% between the two most accurate
      methods (KED-SOC75P and CC-SOC75P) and standard cokriging in which the
      information provided by the aerial photography is ignored when mapping. The
      sensitivity of KED-SOC75P and CC-SOC75P approaches to the sampling density of the
      target variables (TE) was assessed using 10 random subsets of different sizes (25
      and 33 observations) drawn from a prediction set that includes 50 data. Results
      have shown that the TE estimates by KED-SOC75P and CC-SOC75P approaches using
      only 25 TE samples were much more accurate than the estimates performed by OK50
      and COK-TE50SOC75 approaches that use the whole samples of the prediction set.
      Moreover, the RI of accuracy was reduced by less than 15% if the original
      sampling density was reduced by a third.

PMID- 15993473
TI  - Low-energy ultrasound exposure of the streptokinase molecule may enhance but also
      attenuate its fibrinolytic properties.
AB  - INTRODUCTION: This study explores the mechanisms of ultrasound-enhanced
      fibrinolysis by investigating the effects of pre-exposure to pulsed high
      frequency, low-energy ultrasound on the fibrinolytic properties of streptokinase.
      MATERIALS AND METHODS: Fibrinolytic activity was measured as haemoglobin release
      from blood clots. The fibrinolytic effects of streptokinase and ultrasound
      separately and in combination were studied by evaluating cumulative percentages
      of haemoglobin release following 1 h of exposure using two clots, one for
      intervention and the other concomitantly as control. In particular, the effects
      of exposure to ultrasound on clot-free streptokinase solution were compared to
      those of concomitant exposures of streptokinase solution with clot. The exposures
      were made at a frequency of 1 MHz (10% duty cycle) and at three intensity levels
      (0.5, 1.0 and 4.0 W/cm2 intensity I(SATA)). RESULTS: Increased fibrinolysis
      (31.2%, P=0.028) was observed after concomitant ultrasound exposure of clot and
      streptokinase solution at 0.5 W/cm2 intensity. Compared to unexposed
      streptokinase solution, the lytic effect following exposure of streptokinase
      solution to ultrasound was significantly increased (32.7%, P=0.002). This
      enhancement effect disappeared at intensity 1 W/cm2, whilst further increase to
      4.0 W/cm2 inhibited the lytic effect of streptokinase, both during concomitant
      exposure (-25.2%, P=0.028) and after pre-exposure of streptokinase solution to
      ultrasound (-25.4%, P=0.002). CONCLUSION: The fibrinolytic property of
      streptokinase is modulated by exposure to pulsed ultrasound of frequency 1 MHz,
      being enhanced at low intensity and inhibited at high intensity.

PMID- 15993474
TI  - Hypertensive patients with carotid artery plaque exhibit increased platelet
      aggregability.
AB  - BACKGROUND: Platelets play an important role in myocardial infarction and
      ischemic stroke events, but whether platelet aggregability is related to early
      stage arteriosclerosis remains unclear. METHODS: We used a novel platelet
      counting system which makes it possible to detect spontaneous platelet
      aggregation, to evaluate the relationship between platelet aggregability and
      carotid artery arteriosclerosis in 125 outpatients with primary hypertension (46
      73 years old: 65 men, 60 women). All subjects underwent carotid artery
      ultrasonography to determine whether plaque was present and to estimate intima
      media thickness. RESULTS: Patients with carotid artery plaques (Plaque(+), n=63)
      were older and had higher systolic blood pressures than patients without plaques
      (Plaque(-), n=62), but no significant differences in sex, body mass index,
      diastolic blood pressure, plasma concentrations of glucose, total cholesterol,
      triglyceride, lipoprotein cholesterol, fibrinogen or the platelet count in whole
      blood were observed between Plaque(+) and Plaque(-) groups. Plaque(+) subjects
      showed greater spontaneous platelet aggregability and platelet aggregation
      induced by 2 microM or 0.5 microM of ADP or 0.3 microM of epinephrine than the
      Plaque(-) group. When age and systolic blood pressure were matched (n=52 in both
      groups), the Plaque(+) subjects exhibited greater platelet aggregability than the
      Plaque(-) subjects. Platelet aggregation induced by 2 microM of ADP showed
      statistical significant positive correlation coefficients with age, HbA1c and
      diastolic blood pressure. CONCLUSION: Our results indicate that hypertensive
      patients with carotid artery plaque have increased platelet aggregability. A
      prospective study is recommended to clarify whether this increase in platelet
      aggregability promotes the progression of arteriosclerosis.

PMID- 15993475
TI  - The functions of plasminogen activator inhibitor-1: do we have all the pieces of
      PAI?

PMID- 15993476
TI  - Thrombophilia in children with venous thromboembolic disease.
AB  - Venous thromboembolic events (VTEs) in children are usually associated with
      underlying clinical conditions such as central venous line, cancer and cardiac
      diseases. The objective of this review is to present the importance of
      thrombophilia to the occurrence of childhood VTE. The reported prevalence of
      thrombophilia in children with VTE varies extremely between 10% and 78% in
      different registries. The variation in the reported prevalence most probably
      reflects differences in the clinical characteristics of the children studied and
      differences in study designs. The initial management of children with
      thrombophilia and VTE is similar to those individuals who do not have a specific
      inherited thrombophilic risk factor, except in the rare events of homozygous
      deficiencies of prothrombotic coagulation proteins. The impact of thrombophilic
      markers on long-term therapy and outcome of children with VTE has not been
      completely clarified. According to the current guidelines for thrombophilia, all
      children with VTE should be tested for a full panel of genetic and acquired
      prothrombotic traits. However, re-evaluation of co-morbid risk factors other than
      thrombophilic markers and careful consideration of the prognostic value of
      thrombophilic markers might help to change future attitude from the rigidity of
      current guidelines to more rational schemes.

PMID- 15993477
TI  - Effects of estrogen and tamoxifen on the ultrastructural characteristics of
      female rat prolactin cells as evaluated by immunogold technique.
AB  - Estrogens and antiestrogens are known to have effects on prolactin (PRL)
      producing cells in the anterior pituitary. This study was planned to investigate
      the effects of estrogen and tamoxifen at immunohistochemical and immunoelectron
      microscopic levels on PRL cells of female rat pituitary. Animals were divided
      into three groups of eight adult female rats each. The first group was the
      control group. 200-microg/day of estrogen was administered subcutaneously for 11
      weeks to 16 rats. Tamoxifen was administered to eight of them for the last 15
      days. In diethylstilbestrol (DES)-induced group, serum PRL levels and pituitary
      weights were found to be elevated when compared with the control group. In the
      DES plus tamoxifen group the readings were close to that of the control group.
      PRL-positive cells were enlarged and strongly immunostained in DES-induced group
      when assessed by light microscopy. Tamoxifen prevented this effect. At the
      ultrastructural level, in the tamoxifen treated group, PRL-producing cells
      contained both immunopositive and immunonegative secretory granules. Numerous PRL
      producing cells exhibited progressive morphological changes in the nuclei
      compatible with the apoptotic process. The results of this study indicate that
      tamoxifen prevents not only the proliferative effect of estrogen but also
      inhibits the secretion mechanism of the cells.

PMID- 15993478
TI  - Vesicoureteral reflux in adult women with uncomplicated acute pyelonephritis.
AB  - OBJECTIVES: To evaluate the significance of vesicoureteral reflux (VUR) in adult
      women with uncomplicated acute pyelonephritis. METHODS: Eighty-six adult women
      with uncomplicated acute pyelonephritis were studied from April 1998 to October
      2003. They showed no structural urinary tract abnormalities. The mean age of
      patients was 36.2 years (range, 19 to 54 years). We divided these patients into
      two groups. In group I (31 patients), we performed a voiding cystourethrogram
      (VCUG) on the third day of treatment to demonstrate possible transient low-grade
      VUR during the acute infectious phase. In group II (the remaining 55 patients),
      we performed VCUG after the seventh day of treatment. RESULTS: There were only 2
      (2.3%) cases of VUR among 86 patients with uncomplicated acute pyelonephritis. No
      VUR was found in group I, and grade II reflux was found in 2 patients of group
      II. CONCLUSIONS: These results indicate that, unlike in children, VUR is not a
      significant factor causing ascending infection leading to the development of
      acute pyelonephritis in adult women. Further research is warranted regarding the
      pathophysiology of ascending infection in the adult population.

PMID- 15993479
TI  - Access to urologic care for children in California: Medicaid versus private
      insurance.
AB  - OBJECTIVES: To compare the access to urologic care for a child with
      cryptorchidism insured by Medi-Cal versus one insured by private insurance. Medi
      Cal (California State Medicaid) is a joint state and federal health insurance
      program that plays a significant role in providing healthcare coverage to low
      income children. METHODS: A total of 54 randomly chosen urology offices
      throughout California were surveyed by telephone to determine whether the office
      accepted pediatric patients, accepted Medi-Cal, and when the earliest appointment
      date would be for a patient with Medi-Cal versus one with private insurance.
      RESULTS: Of the 46 practices that accepted pediatric patients, 96% offered a new
      patient appointment to a child with private insurance, but only 41% were willing
      to offer an appointment to a child with Medi-Cal (P < 0.0001). Of the offices
      that would not see a child with Medi-Cal, 75% were unable to recommend a urology
      office that might accept Medi-Cal. CONCLUSIONS: Children insured by Medi-Cal have
      significantly less access to necessary urologic care compared with children with
      private insurance.

PMID- 15993480
TI  - Aberrant expression and mutations of TGF-beta receptor type II gene in
      endometrial cancer.
AB  - OBJECTIVE: Transforming growth factor beta (TGF-beta) is a multifunctional
      cytokine that strongly inhibits epithelial cell growth. Disabling of TGF-beta
      signaling is thought to be involved in development of a variety of tumors in
      which abnormal expression or function of TGF-beta receptor plays critical roles.
      In the present study, we examined aberrant expression and mutation of the gene
      TGF-beta receptor type II (TbetaRII) in endometrial cancers of endometrioid
      subtype. METHODS AND RESULTS: Real-time PCR analysis using surgical tissue
      specimens of 27 endometrial cancers and 24 normal endometria revealed that
      endometrial cancers had significantly decreased levels of TbetaRII mRNA
      expression (mean level 2.44 +/- 2.65), compared to normal endometria (mean level
      7.23 +/- 6.07) (P < 0.001). Methylation status of TbetaRII promoter containing 30
      CpGs was examined by bisulfite sequencing analysis, and 98% (51/52) of the
      patients were found to have unmethylated TbetaRII promoter, indicating that
      promoter hypermethylation is not the major cause of decreased expression of
      TbetaRII in endometrial cancers. Mutational analysis revealed that 15.1% (8/53)
      of endometrial cancers had frameshift mutations at polyadenine repeats in exon 3
      of the TbetaRII gene. Notably, these mutations were preferentially accumulated in
      patients with MSI-H phenotype (7/19:37%) (P < 0.001) or with those with
      methylated MLH1 promoters (6/16:38%) (P < 0.01). Thus, it appears that the
      TbetaRII gene is a target of mismatch repair deficiency. CONCLUSION: Taken
      together, we found that the decreased expression of TbetaRII as well as
      frameshift mutation of TbetaRII via mismatch repair deficiency frequently occurs
      in this tumor type, possibly causing loss of receptor function and
      unresponsiveness of TGF-beta signaling that may lead to endometrial
      carcinogenesis.

PMID- 15993481
TI  - Equine fetal gender determination from mid- to advanced-gestation by ultrasound.
AB  - Equine fetal gender can be easily determined by ultrasound between Days 120 and
      210. A combination of transrectal and transabdominal ultrasound examinations can
      visualise fetal sex organs up to 8 months of gestation. Early equine fetal sexing
      techniques, performed between approximately Days 58 and 70, are aimed at
      identifying the position of the genital tubercle. A wider diagnostic window, a
      diagnosis based on several parameters, and the ease of identification of fully
      developed fetal primary sex organs make gender diagnosis in mid- to advanced
      gestation a preferable technique.

PMID- 15993482
TI  - Semen collection in the dog.
AB  - This review will discuss semen collection in the dog. Semen samples may be
      collected from male dogs for the purposes of artificial insemination,
      cryopreservation or diagnosis. The materials needed for semen collection depend
      on which method is used and the collector's level of expertise with this
      procedure. At minimum, two sterile centrifuge tubes or specimen cups can be used
      to collect semen as it is ejaculated (for the combined first and second fractions
      and for the third fraction). The most common method for semen collection in the
      dog is by digital stimulation. Under ideal conditions, this procedure is
      performed in the presence of an estrous bitch. Initially, the dog's penis is
      vigorously massaged through the prepuce at the level of the bulbus glandis
      (caudal-most aspect of the prepuce) until a partial erection develops (initial
      engorgement of the bulbus glandis). The prepuce is quickly retracted past the
      bulbus glandis and firm constant pressure is applied to the penis behind the
      bulbus glandis by squeezing the penis between index finger and thumb. Pelvic
      thrusting may occur following application of pressure behind the bulbus glandis
      during the development a "full" erection. The ejaculate is composed of three
      fractions: first (sperm-poor), second (sperm-rich) and third (prostatic fluid).
      In addition to digital stimulation of the penis, spermatozoa have been collected
      from dogs using electroejaculation and pharmacologic methods.

PMID- 15993483
TI  - An in vitro study on spontaneous myometrial contractility in the mare during
      estrus and diestrus.
AB  - Uterine smooth muscle specimens were collected from euthanatized mares in estrus
      and diestrus. Longitudinal and circular specimens were mounted in organ baths and
      the signals transcribed to a Grass polygraph. After equilibration time and 2 g
      preload, their physiologic isometric contractility was recorded for a continuous
      2.0 h. Area under the curve, frequency and time occupied by contractions were
      studied. Differences between cycle phases, between muscle layers, and over the
      recorded time periods were statistically evaluated using linear mixed-effect
      models. In the mare, physiologic contractility of the uterus decreased
      significantly over time for all variables evaluated (time as covariate on a
      continuous scale). For area under the curve, there was a significant effect of
      muscle layer (longitudinal > circular). For frequency, higher values were
      recorded in estrus for circular smooth muscle layer, whereas higher values were
      seen in longitudinal smooth muscle layers during diestrus. In longitudinal layer
      and in diestrus, more time was occupied by contractions than in circular layer,
      and in estrus. This study is describing physiologic myometrial motility in the
      organ bath depending on cycle phase.

PMID- 15993484
TI  - Brief report: adaptation of the Italian Version of the Tromso Social Intelligence
      Scale to the adolescent population.
AB  - Social intelligence is a construct that has shown promising practical
      applications, but its use in research and applied settings has been limited by
      definitional problems and the complexity of most existing measures of social
      intelligence. The goal of the present study was to adapt the Italian version
      [Gini & Iotti (2004) La Tromso Social Intelligence Scale: Traduzione e
      adattamento alla popolazione Italiana. Italy: University of Padova.] of the
      Tromso Social Intelligence Scale, TSIS [Silvera, Martinussen, & Dahl (2001).
      Scandinavian Journal of Psychology, 42, 313-319.] to the adolescent population
      (the sample comprised 320 Italian adolescents, 132 boys and 188 girls). Our
      analyses revealed the same factorial structure of the original scale and showed a
      good internal reliability. The items of the TSIS-IV were reasonably unbiased in
      terms of social desirability response bias.

PMID- 15993485
TI  - Sol-gel synthesis of a multifunctional, hierarchically porous silica/apatite
      composite.
AB  - In this study, a degradable, hierarchically porous silica/apatite composite
      material is developed from a simple low-temperature synthesis. Mesoporosity is
      induced in the silica portion by the use of supramolecular templating. The
      template is further removed by calcination. Firstly, hydroxyapatite is
      synthesized through a sol-gel method at near room temperature conditions. After
      the mineralization process, the crystal surface is coated with a mesoporous
      silica matrix using the templates already present in the bulk solution. The
      material is characterized by XRD, N(2)-sorption, FT-IR, SEM/EDS, and TEM. The
      coating layer is distributed fairly homogeneously over the apatite surface and
      the coating thickness is easily adjustable and dependent on the amount of added
      silica precursor. The hybrid material is shown to efficiently induce calcium
      phosphate formation under in vitro conditions and simultaneously work as a
      carrier system for drugs.

PMID- 15993486
TI  - Generation of cell adhesive substrates using peptide fluoralkyl surface
      modifiers.
AB  - Previous studies reported on the delivery of vitamin E to the surface of a
      polycarbonate polyurethane (PCNU) to produce antioxidant surfaces, using a
      bioactive fluorinated surface modifer (BFSM). In the current report, a cell
      adhesive peptide sequence was coupled to the BFSM, and when blended into PCNU,
      generated a cell adhesive substrate. An NH2-GK*GRGD-CONH2 peptide sequence
      (referred to as RGD) with a dansyl label (*) on the lysine residue was coupled
      via the N-terminal to a BFSM precursor molecule. The resulting RGD BFSM was
      purified and the pmol peptide/mg BFSM value was assayed by amino acid
      quantification. The migration of the RGD BFSM in a PCNU blend was confirmed by X
      ray photoelectron spectroscopy analysis. U937 macrophage-like cells and human
      monocytes were seeded onto the PCNU and blends of PCNU with non-bioactive
      fluorinated surface modifier or the RGD BFSM, in order to study the cell
      response. Both U937 cells and human monocytes adhered in greater numbers to the
      RGD BFSM substrate when compared to unmodified PCNU or the blend of PCNU with the
      non-bioactive fluorinated surface modifying macromolecule substrate. The study
      demonstrated a novel approach for the introduction of peptides onto the surface
      of polymers by modifying the surface from within the polymer as opposed to the
      use of cumbersome post-surface modification techniques. The generation of a
      peptide substrate points to the possibility of producing complex bioactive
      surfaces using various peptide BFSMs or pharmaceuticals simultaneously to
      manipulate cell functions.

PMID- 15993487
TI  - Characterization of irradiated blends of alpha-tocopherol and UHMWPE.
AB  - Adhesive/abrasive wear in ultra-high molecular weight polyethylene (UHMWPE) has
      been minimized by radiation cross-linking. Irradiation is followed by melting to
      eliminate residual free radicals and avoid long-term oxidative embrittlement.
      However, post-irradiation melting reduces the crystallinity of the polymer and
      hence its strength and fatigue resistance. We proposed an alternative to post
      irradiation melting to be the incorporation of the antioxidant alpha-tocopherol
      into UHMWPE prior to consolidation. alpha-Tocopherol is known to react with
      oxygen and oxidized lipids, stabilizing them against further oxidative
      degradation reactions. We blended GUR 1050 UHMWPE resin powder with alpha
      tocopherol at 0.1 and 0.3 wt% and consolidated these blends. Then we gamma
      irradiated these blends to 100-kGy. We characterized the effect of alpha
      tocopherol on the cross-linking efficiency, oxidative stability, wear behavior
      and mechanical properties of the blends. (I) The cross-link density of virgin,
      0.1 and 0.3 wt% alpha-tocopherol blended, 100-kGy irradiated UHMWPEs were 175+/
      19, 146+/-4 and 93+/-4 mol/m3, respectively. (II) Maximum oxidation indices for
      100-kGy irradiated UHMWPE previously blended with 0, 0.1 and 0.3 wt% alpha
      tocopherol that were subjected to accelerated aging at 80 degrees C in air for 5
      weeks were 3.32, 0.09, and 0.05, respectively. (III) The pin-on-disc wear rates
      of 100-kGy irradiated UHMWPE previously blended with 0.1 and 0.3 wt% alpha
      tocopherol that were subjected to accelerated aging at 80 degrees C in air for 5
      weeks were 2.10+/-0.17 and 5.01+/-0.76 mg/million cycles, respectively. (IV) Both
      accelerated aged, alpha-tocopherol-blended 100-kGy irradiated UHMWPEs showed
      higher ultimate tensile strength, higher yield strength, and lower elastic
      modulus when compared to 100-kGy irradiated, virgin UHMWPE. These results showed
      that alpha-tocopherol-blended 100-kGy irradiated UHMWPEs were not cross-linked to
      the same extent as the 100-kGy irradiated, virgin UHMWPE.

PMID- 15993488
TI  - Deposition of PCBs in mountains: the forest filter effect of different forest
      ecosystem types.
AB  - The effect of canopy composition and density on the forest filter effect (the
      deposition flux under the canopy and deposition to bare soil) for polychlorinated
      biphenyls (PCBs) was investigated for forests of the Italian Alps. Deposition
      fluxes were measured in situ using deposition samplers below canopies and in
      adjacent clearings at three altitudes (1100, 1400, and 1800 m above sea level).
      Forest sites were selected on the basis of canopy composition and density. Net
      forest fluxes (NFFs) were calculated by subtracting the deposition flux under
      canopies by deposition fluxes to clearings and represent the net contribution of
      forests to PCB deposition. NFF trends are discussed in relation to canopy
      development. Mean deposition velocities were also calculated and a direct
      correlation with the/octanol air partition coefficient (K(OA)) was found. A leaf
      area index (LAI) was used to calculate a specific, canopy density-independent,
      deposition velocity for each forest type. This parameter can be used to calculate
      the deposition of PCBs in forests, given their LAI. Results show that forests
      significantly enhance the deposition of PCBs to soil and that this effect is
      controlled by temperature, leaf dynamics, and K(OA).

PMID- 15993489
TI  - Toxicity of a cyanobacteria bloom in Barra Bonita Reservoir (Middle Tiete River,
      Sao Paulo, Brazil).
AB  - In eutrophic waters during cyanobacterial bloom lysis, a blend of cyanobacterial
      toxins and other compounds are released into the water, affecting aquatic
      communities. This research investigated the effect of a simulated cyanobacterial
      lysis event. For this purpose, intact cells from a natural cyanobacterial bloom
      from Barra Bonita Reservoir (Tiete River basin, Brazil) were taken, and the cells
      were broken by repeated freeze/thaw cycles. The toxicity of the crude
      cyanobacterial extract was investigated using cladocerans (Daphnia similis and
      Ceriodaphnia silvestrii), and the hepatotoxicity of the cyanobacterial
      lyophilized material was confirmed by mouse bioassay. The results obtained using
      D. similis and C. silvestrii acute bioassays indicated 24-h LC(50) values of
      186.61 and 155.11 mg L(-1), respectively. The 24-h LD(50) determined by
      intraperitoneal injection into mice was 445.45 mg dry kg(-1). Microcystin content
      was 311 microgg(-1) dry wt freeze-dried cyanobacteria. The acute tests with
      cladocerans were effective in indicating the toxicity of the crude cyanobacterial
      extract and in prognostiating the toxic effects of cyanobacterial blooms, at
      least on some usual components of the aquatic community, such as
      microcrustaceans.

PMID- 15993490
TI  - A case study on identification of airborne organic compounds and time courses of
      their concentrations in the cabin of a new car for private use.
AB  - The cabin of an automobile can be considered to be a part of the living
      environment because many people spend long periods of time during business,
      shopping, recreation or travel activities. However, little is known about the
      interior air contamination due to organic compounds diffusing from the interior
      materials used in the interior of automobiles. In the present study, the
      compounds in the interior air of a new car were identified, and the time courses
      of their concentrations were examined for over 3 years after the delivery (July,
      1999). A total of 162 organic compounds, involving many aliphatic hydrocarbons
      and aromatic hydrocarbons, were identified. High concentrations of n-nonane (458
      microg/m(3) on the day following delivery), n-decane (1301 microg/m(3)), n
      undecane (1616 microg/m(3)), n-dodecane (716 microg/m(3)), n-tridecane (320
      microg/m(3)), 1-hexadecene (768 microg/m(3)), ethylbenzene (361 microg/m(3)),
      xylene (4003 microg/m(3)) and 2,2'-azobis(isobutyronitrile) (429 microg/m(3))
      were detected, and the sum of the concentrations determined for all compounds
      excluding formaldehyde (TVOC) was approximately 14 mg/m(3) on the day after the
      delivery. The concentrations of most compounds decreased with time, but increased
      with a rise of the interior temperature. The TVOC concentration in the next
      summer (July, 2000) was approximately one-tenth of the initial concentration.
      During the 3-year study period, the TVOC concentrations in summer exceeded the
      indoor guideline value (300 mug/m(3)) proposed by [Seifert B. Volatile organic
      compounds. In: Maroni M, Seifert B, Lindvall T, editors. Indoor air quality. A
      comprehensive reference book. Air quality monographs, vol. 3. Netherlands:
      Elsevier Science; 1995. p. 819-21]. The interior temperature and days lapsed
      after delivery were the main factors affecting the interior concentrations of
      most compounds according to multiple linear regression analysis. The results of
      this study offer useful fundamental data for investigations on air pollution in
      automotive cabins due to the organic compounds diffusing from the interior
      materials.

PMID- 15993491
TI  - No changes in serum epidermal growth factor levels in patients with
      schizophrenia.
AB  - A recent report demonstrated that serum levels of epidermal growth factor (EGF)
      were significantly decreased in patients with schizophrenia, suggesting that
      impaired EGF signaling might be associated with the pathophysiology of
      schizophrenia. Our goal in the present study was to determine whether serum
      levels of EGF are altered in patients with schizophrenia. We found that serum
      levels of EGF in drug-naive (n = 15) or medicated patients (n = 25) with
      schizophrenia did not differ from those of age- and sex-matched normal controls
      (n = 40). However, we found a significant correlation between serum EGF levels
      and BPRS scores in the combined groups of patients. Therefore, our results do not
      support the claim that EGF plays a role in the pathogenesis of schizophrenia, but
      they suggest that EGF may serve as a state marker, that is, as an index of
      symptom-linked deficits.

PMID- 15993492
TI  - Iron modulates the replication of virulent Mycobacterium bovis in resting and
      activated bovine and possum macrophages.
AB  - Bovine and possum macrophages were infected in vitro with a virulent strain of
      Mycobacterium bovis, and mycobacterial replication was measured in the infected
      macrophages cultured under a variety of conditions. Virulent M. bovis replicated
      substantially in alveolar possum macrophages as well as in bovine blood monocyte
      derived macrophages. Addition of recombinant bovine interferon-gamma (IFN-gamma)
      with low concentrations of lipopolysaccharide (LPS) rendered bovine macrophages
      significantly more resistant to M. bovis replication. Disruption of iron levels
      in infected macrophages by addition of apotransferrin or bovine lactoferrin
      blocked replication of M. bovis in both bovine and possum macrophages. On the
      other hand, addition of exogenous iron, either in the form of iron citrate or
      iron-saturated transferrin, rendered macrophages of both species much more
      permissive for the replication of M. bovis. The impact of iron
      deprivation/loading on the mycobacteriostatic activity of cells was independent
      of nitric-oxide release, as well as independent of the generation of oxygen
      radical species in both possum and bovine macrophages. Exogenous iron was shown
      to reverse the ability of IFN-gamma/LPS pulsed bovine macrophages to restrict M.
      bovis replication. When autologous possum lymphocytes from animals vaccinated
      with M. bovis strain BCG were added to infected macrophages, they rendered the
      macrophages less permissive for virulent M. bovis replication. Loading the cells
      with iron prior to this macrophage-lymphocyte interaction, reversed this immune
      effect induced by sensitized cells. We conclude that, in two important animal
      species, intracellular iron level plays an important role in M. bovis replication
      in macrophages, irrespective of their activation status.

PMID- 15993493
TI  - The G-protein coupled receptor, GPR84 regulates IL-4 production by T lymphocytes
      in response to CD3 crosslinking.
AB  - The orphan G-protein coupled receptor, GPR84 is highly expressed in the bone
      marrow, and in splenic T cells and B cells. In this study, GPR84-deficient mice
      were generated to understand the biological function of this orphan receptor. The
      proliferation of T and B cells in response to various mitogens was normal in
      GPR84-deficient mice. Interestingly, primary stimulation of T cells with anti-CD3
      resulted in increased IL-4 but not IL-2 or IFN-gamma production in GPR84(-/-)
      mice compared to wild-type mice. Augmented IL-4 production in GPR84-deficient T
      cells was not related to increased frequency of IL-4-secreting cells in response
      to anti-CD3 stimulation. In fact, stimulation with anti-CD3 and anti-CD28
      resulted in increased levels of IL-4 but not IFN-gamma steady-state mRNA in
      GPR84(-/-) T cells. In addition, Th2 effector cells generated in vitro from
      GPR84(-/-) mice produced higher levels of IL-4, IL-5 and IL-13 compared to wild
      type mice. However, there was no detectable difference in the extent of IL-4 and
      IL-5 production between the two groups of mice in response to antigen stimulation
      of spleen cells, isolated from mice previously immunized with OVA in alum. These
      studies reveal a novel role for GPR84 in regulating early IL-4 gene expression in
      activated T cells.

PMID- 15993494
TI  - Antibodies induced by ganglioside-mimicking Campylobacter jejuni
      lipooligosaccharides recognise epitopes at the nodes of Ranvier.
AB  - Molecular mimicry of gangliosides by Campylobacter jejuni lipooligosaccharides
      (LOSs) in the induction of anti-ganglioside antibodies has been hypothesised to
      contribute to GBS development. Rabbits were immunised with ganglioside-mimicking
      C. jejuni LOSs and anti-LOS responses were analysed using passive
      haemagglutination, and anti-ganglioside responses by enzyme-linked immunosorbent
      assay and thin-layer chromatography with immunostaining. High titres of anti-LOS
      antibodies were demonstrated in rabbit antisera that were cross-reactive with a
      panel of gangliosides. Non-ganglioside-mimicking C. jejuni HS:3 LOS induced a
      strong anti-LOS response, but no anti-ganglioside antibodies. Control rabbit
      antisera had no anti-LOS or -ganglioside responses. Moreover, IgG from a patient
      treated with parenteral gangliosides, who exhibited Guillain-Barre syndrome, had
      antibodies reactive with C. jejuni LOS. Biotinylated IgG fractions from the
      rabbit and the patient sera recognised epitopes at the nodes of Ranvier in
      sectioned human nerves, whereas fractions from controls did not. This study
      demonstrates that immunisation with ganglioside-mimicking C. jejuni LOS triggers
      the production of cross-reactive anti-ganglioside antibodies that recognise
      epitopes at the nodes of Ranvier.

PMID- 15993495
TI  - Tissue-specific accumulation of cadmium in subcellular compartments of eastern
      oysters Crassostrea virginica Gmelin (Bivalvia: Ostreidae).
AB  - Cadmium distribution was studied in different subcellular fractions of gill and
      hepatopancreas tissues of eastern oysters Crassostrea virginica. Oysters were
      exposed for up to 21 days to low sublethal Cd concentrations (25 microg L(-1)).
      Gill and hepatopancreas tissues were sampled and divided into organelle fractions
      and cytosol by differential centrifugation. Organelle content of different
      fractions was verified by activities of marker enzymes, citrate synthase and acid
      phosphatase for mitochondria and lysosomes, respectively. In both tissue types,
      there was a significant accumulation of cadmium in cytosol reaching 230-350 ng
      mg(-1) protein. Among organelles, mitochondria were the main target for Cd
      bioaccumulation in gills (250-300 ng mg(-1) protein), whereas in hepatopancreas
      tissues, the highest cadmium accumulation occurred in lysosomes (90-94 ng mg(-1)
      protein). Although 75-83% of total cadmium burden was associated with the cytosol
      reflecting high volume fraction of this compartment, Cd concentrations in
      organelle fractions reached levels that could cause dysfunction of mitochondria
      and lysosomes. Organ- and organelle-specific patterns of cadmium bioaccumulation
      support our previous in vivo studies, which showed adverse effects of cadmium
      exposures on mitochondrial oxidation in gills and on the lysosomal system of
      hepatopancreas. This may have important implications for the development of
      biomarkers of effect for heavy metals and for understanding the mechanisms of
      toxic effects of metals.

PMID- 15993496
TI  - Messenger RNA processing sites in Trypanosoma brucei.
AB  - In Kinetoplastids, protein-coding genes are transcribed polycistronically by RNA
      polymerase II. Individual mature mRNAs are generated from polycistronic
      precursors by 5' trans splicing of a 39-nt capped leader RNA and 3'
      polyadenylation. It was previously known that trans splicing generally occurs at
      an AG dinucleotide downstream of a polypyrimidine tract, and that polyadenylation
      is coupled to downstream trans splicing. The few polyadenylation sites that had
      been examined were 100-400 nt upstream of the polypyrimidine tract which marked
      the adjacent trans splice site. We wished to define the sequence requirements for
      trypanosome mRNA processing more tightly and to generate a predictive algorithm.
      By scanning all available Trypanosoma brucei cDNAs for splicing and
      polyadenylation sites, we found that trans splicing generally occurs at the first
      AG following a polypyrimidine tract of 8-25 nt, giving rise to 5'-UTRs of a
      median length of 68 nt. We also found that in general, polyadenylation occurs at
      a position with one or more A residues located between 80 and 140 nt from the
      downstream polypyrimidine tract. These data were used to calibrate free
      parameters in a grammar model with distance constraints, enabling prediction of
      polyadenylation and trans splice sites for most protein-coding genes in the
      trypanosome genome. The data from the genome analysis and the program are
      available from: .

PMID- 15993497
TI  - Signaling via NF-kappaB in the nervous system.
AB  - Nuclear factor kappa B (NF-kappaB) is an inducible transcription factor present
      in neurons and glia. Recent genetic models identified a role for NF-kappaB in
      neuroprotection against various neurotoxins. Furthermore, genetic evidence for a
      role in learning and memory is now emerging. This review highlights our current
      understanding of neuronal NF-kappaB in response to synaptic transmission and
      summarizes potential physiological functions of NF-kappaB in the nervous system.
      This article contains a listing of NF-kappaB activators and inhibitors in the
      nervous system, furthermore specific target genes are discussed. Synaptic NF
      kappaB activated by glutamate and Ca2+ will be presented in the context of
      retrograde signaling. A controversial role of NF-kappaB in neurodegenerative
      diseases will be discussed. A model is proposed explaining this paradox as
      deregulated physiological NF-kappaB activity, where novel results are integrated,
      showing that p65 could be turned from an activator to a repressor of anti
      apoptotic genes.

PMID- 15993498
TI  - Differential subcellular distribution of estrogen receptor isoforms: localization
      of ERalpha in the nucleoli and ERbeta in the mitochondria of human osteosarcoma
      SaOS-2 and hepatocarcinoma HepG2 cell lines.
AB  - The localization of estrogen receptors alpha (ERalpha) and beta (ERbeta) in
      osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cells was studied by
      immunofluorescence labelling and confocal laser scanning microscopy, as well as
      by subcellular fractionation and immunoblotting of the proteins of the fractions
      with respective antibodies. In both cell types, ERalpha was localized mainly in
      the nucleus, particularly concentrated on nuclear structures, which on the basis
      of their staining with pyronin and with antibodies against the nucleoli-specific
      Ki67 antigen and C23-nucleolin, were characterized as nucleoli. A faint, diffuse
      ERalpha staining was also observed in the cytoplasm. ERbeta was specifically
      enriched at the site of the mitochondria, visualized by labelling with the vital
      dye CMX and antibody against the mitochondrial-specific cytochrome oxidase
      subunit I. Immunoblotting experiments corroborated the immunofluorescence
      labelling distribution of ERalpha and ERbeta. These findings support the concept
      of a direct action of steroid/thyroid hormones on mitochondrial functions by way
      of their cognate receptors and also suggest a direct involvement of ERalpha in
      nucleolar-related processes.

PMID- 15993499
TI  - Transient impairment of flow-mediated vasodilation in patients with metabolic
      syndrome at moderate altitude (1,700 m).
AB  - BACKGROUND: The influence of moderate altitude on the cardiovascular system in
      patients with metabolic syndrome has not been investigated sufficiently, yet. The
      aim of this study was to assess the effect of acute and mid-term exposure to
      moderate altitude (1,700 m) on endothelial function in patients with metabolic
      syndrome. METHODS: Flow-mediated (FMD) and nitroglycerin-mediated vasodilation
      (NMD) were assessed in 18 patients with coronary risk factors on 5 occasions: (1)
      at location A (576 m), (2) on the first day at moderate altitude (location B,
      1,700 m), (3) after 3 weeks at moderate altitude, (4) and (5) again at location A
      (6 and 16 weeks after the stay at moderate altitude, respectively). In addition,
      markers of lipid metabolism, serum erythropoietin and endothelin were measured.
      RESULTS: FMD on the first day at moderate altitude was similar compared to
      baseline FMD at location A (7.0 +/- 3.3 vs. 7.4 +/- 4.6%; NS). A 3-week stay at
      moderate altitude was associated with a significant reduction in FMD (7.4 +/- 4.6
      vs. 3.8 +/- 2.5%; p < 0.05) despite a decrease in baseline diameter (4.5 +/- 0.3
      vs. 4.3 +/- 0.4 mm; p < 0.05). Six weeks after returning to location A, FMD was
      still reduced compared to baseline (4.3 +/- 2.8%; p < 0.05) and after further 16
      weeks, FMD returned to baseline values (5.5 +/- 3.5%). However, metabolic
      parameters improved significantly. In contrast, NMD and endothelin levels
      remained unchanged. CONCLUSION: In patients with metabolic syndrome, a sojourn of
      3 weeks at moderate altitude leads to a prolonged, but reversible impairment of
      FMD. The discrepancy to improvement of other cardiovascular and metabolic
      parameters requires further investigation.

PMID- 15993500
TI  - Midventricular hypertrophic cardiomyopathy coexistent with anomalous origin of
      circumflex artery.

PMID- 15993501
TI  - A comparison of low versus high heart rate in patients with atrial fibrillation
      and advanced chronic heart failure: effects on clinical profile, neurohormones
      and survival.
AB  - BACKGROUND: Atrial fibrillation is common in chronic heart failure. Long-term
      restoration of sinus rhythm is generally unsuccessful. It may be speculated that
      higher heart rates are unfavorable, since this may lead to tachycardiomyopathy,
      but there are no data which have examined this. METHODS AND RESULTS: Seventy
      seven patients with atrial fibrillation and advanced chronic heart failure, age
      70 +/- 7 years, left-ventricular ejection fraction 0.23 +/- 0.08, 61% with
      ischemic etiology were included. Patients were dichotomized according to the
      median heart rate (80 bpm) at inclusion (39 patients with "low" heart rate and 38
      patients with "high" heart rate). At baseline, both patient groups were
      remarkably comparable. After a mean follow-up of 3.3 +/- 0.9 years, mortality was
      comparable (62% versus 55%, p = non-significant). An independent relation was
      found between lower heart rate and survival, in addition to absence of
      hypertension, digoxin use, and higher N-ANP, dopamine, and renin levels.
      CONCLUSION: In the present analysis, patients with atrial fibrillation and
      advanced chronic heart failure with higher heart rates are comparable to those
      with lower heart rates. Not higher heart rates at baseline but, on the contrary,
      lower heart rates seem associated with a worse outcome.

PMID- 15993502
TI  - Seropositivity to Chlamydia pneumoniae or Helicobacter pylori and coronary artery
      disease.
AB  - Our aim was to investigate the relationship between the serologic status
      concerning Chlamydia pneumoniae and Helicobacter pylori with the presence of
      coronary artery disease (CAD), which remain a controversial issue in literature.
      We studied 208 patients with CAD and 94 controls with no evidence of obstructive
      CAD; all of them angiographically confirmed. The seropositivity to C. pneumoniae
      was 91% in patients with CAD vs 86% in controls (P>0.05). The H. pylori
      seroprevalence rates were 77% and 68%, respectively (P>0.05). The multivariate
      analysis, adjusting for age, sex, educational level, diabetes, hypertension,
      obesity, smoking, family history of CAD and lipids, confirmed the results of
      univariate analysis. Therefore, this study adds evidence against the association
      of seropositivity to C. pneumoniae and H. pylori with angiographically documented
      CAD.

PMID- 15993503
TI  - Site-directed genome modification: derivatives of DNA-modifying enzymes as
      targeting tools.
AB  - The modification of mammalian genomes is an important goal in gene therapy and
      animal transgenesis. To generate stable genetic and biochemical changes, the
      therapeutic genes or transgenes need to be incorporated into the host genome.
      Ideally, the integration of the foreign gene should occur at sites that ensure
      their continual expression in the absence of any unwanted side effects on
      cellular metabolism. In this article, we discuss the opportunities provided by
      natural DNA-modifying enzymes, such as transposases, recombinases and integrases,
      to mediate the stable integration of foreign genes into host genomes. In
      addition, we discuss the approaches that have been taken to improve the
      efficiency and to modify the site-specificity of these enzymes.

PMID- 15993504
TI  - Development of an enzyme-linked immunoreceptor assay (ELIRA) for quantification
      of the biological activity of recombinant human bone morphogenetic protein-2.
AB  - Human bone morphogenetic protein-2 is a representative of the transforming growth
      factor-beta (TGF-beta) superfamily of cytokines. It was produced in high-cell
      density cultivations of recombinant Escherichia coli leading to the formation of
      inclusion bodies with aggregated inactive protein so that the protein had to be
      solubilized and renatured. Thus, the biological activity of the recombinant
      protein had to be determined. To avoid time-consuming cell-based assays or
      radioactive labelling of proteins enzyme-linked immunoreceptor assays were
      developed. They were based on the specific interaction between the biologically
      active protein and its receptors, of which the extracellular ligand binding
      domains were tagged with the Fc part of human IgG and expressed in insect cells.
      The amount of bound ligand, corresponding to the biologically active recombinant
      protein, was determined via enzyme-labelled antibodies. Application to various
      batches of protein showed that not only the amount of active protein could be
      quantified but also the quality of the protein preparations could be evaluated in
      significantly shorter analysis times than with conventional cell-based assays.

PMID- 15993505
TI  - Proposal for a better integration of bacterial lysis into the production of
      plasmid DNA at large scale.
AB  - The paper addresses the question of how to achieve bacterial lysis in large-scale
      plasmid DNA production processes, where conventional alkaline lysis may become
      awkward to handle. Bacteria were grown in shaker flasks and a bioreactor.
      Suboptimal growth conditions were found advantageous for stable plasmid
      production at high copy numbers (up to 25mg/L could be achieved). Cells were
      harvested by filtration in the presence of a filter aid. A linear relationship
      between the biomass and the optimal filter aid concentration in terms of back
      pressure could be established. Bacteria-containing filter cakes were washed with
      isotonic buffer and lysis was achieved in situ by a two-step protocol calling for
      fragilisation of the cells followed by heat lysis in a suitable buffer. RNA and
      other soluble cell components where washed out of the cake during this step,
      while the plasmid DNA was retained. Afterwards a clear lysate containing
      relatively pure plasmid DNA could be eluted from the cake mostly as the desired
      supercoiled topoisomer, while cell debris and genomic DNA were retained. Lysis
      is, thus, integrated not only with cell capture but also with a significant
      degree of isolation/purification, as most impurities were considerably reduced
      during the procedure.

PMID- 15993506
TI  - Coxsackievirus B3 replication is related to activation of the late extracellular
      signal-regulated kinase (ERK) signal.
AB  - MAP kinase signaling has been implicated in coxsackievirus B3 (CVB3) pathogenesis
      and as necessary in the virus lifecycle. We studied the correlation with
      extracellular signal-regulated kinase 1/2 (ERK1/2) signaling and virus
      replication in the presence of coxsackievirus and adenovirus receptor (CAR). In
      CHO cells that do not expressed CAR, specific ERK1/2 phosphorylation (pERK1/2)
      was not detected, and progeny virus was not produced after infection. By
      contrast, in HeLa and CHO-CAR cells, which expressed CAR, the specific early and
      late pERK1/2 at 0.5 and 8 h were induced, and progeny viruses were produced
      progressively through 24 h after infection. However, when CHO-CAR cells were
      infected with replication-defective CVB3, specific pERK1/2 was not detected. In
      addition, when late pERK1/2 is inhibited by the MEK1 inhibitor PD98059, at 4 h
      after infection, virus replication significantly decreased. Therefore, our
      findings suggest that early pERK1/2 is a response to virus binding to CAR,
      whereas late pERK1/2 is related to the viral replication.

PMID- 15993507
TI  - Long-term delivery of superoxide dismutase and catalase entrapped in poly(lactide
      co-glycolide) microspheres: in vitro effects on isolated neonatal porcine
      pancreatic cell clusters.
AB  - To counterbalance the restricted availability of pancreatic islet tissue for
      transplant in Type 1 Diabetes Mellitus (T1DM), new methods to provide viable and
      functional islet cells need to be established. We report on our approach to
      enhance in vitro viability and function of isolated neonatal pancreatic porcine
      cell clusters (NPCCs) by co-culturing them with PLGA microsphere entrapped,
      slowly release superoxide dismutase and catalase. These powerful antioxidizing
      agents were shown to significantly improve morphology, viability and function, as
      assessed by microscopy, molecular, biochemical and functional studies, of the
      incubated NPCCs, as compared to control. Preliminarily, in vitro exposure of
      isolated NPCCs to slow release microsphere-embedded SOD and CAT could permit or
      contribute to overcome hurdles associated with scarcity in islet tissue
      procurement for transplant in T1DM.

PMID- 15993508
TI  - Precipitation casting of drug-loaded microporous PCL matrices: incorporation of
      progesterone by co-dissolution.
AB  - Microporous, poly(epsilon-caprolactone) (PCL) matrices were loaded with
      progesterone by precipitation casting using co-solutions of PCL and progesterone
      in acetone. Progesterone loadings up to 32% w/w were readily achieved by
      increasing the drug content of the starting PCL solution. The kinetics of steroid
      release in PBS at 37 degrees C over 10 days could be described effectively by a
      diffusional release model although the Korsmeyer-Peppas model indicated the
      involvement of multiple release phenomena. The diffusion rate constant (D)
      increased from 8 to 24 microg/mg matrix/day0.5 as the drug loading increased from
      3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high
      efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39
      g/cm3, by increasing the starting PCL solution concentration, was less effective
      in changing drug release kinetics. Retention of anti-proliferative activity of
      released steroid was confirmed using cultures of breast cancer epithelial (MCF-7)
      cells. Progesterone released from PCL matrices into PBS at 37 degrees C over 14
      days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with
      progesterone-free controls. These findings recommend further investigation of
      precipitation-cast PCL matrices for delivery of bioactive molecules such as anti
      proliferative agents from implanted, inserted or topical devices.

PMID- 15993509
TI  - [Spinal manipulations].

PMID- 15993510
TI  - Targeted gene transfer to nigrostriatal neurons in the rat brain by helper virus
      free HSV-1 vector particles that contain either a chimeric HSV-1 glycoprotein C
      GDNF or a gC-BDNF protein.
AB  - Direct gene transfer into neurons has potential for both studying neuronal
      physiology and for developing gene therapy treatments for specific neurological
      conditions. Due to the heterogeneous cellular composition of the brain, cell-type
      specific recombinant gene expression is required for many potential applications
      of neuronal gene transfer. The two prevalent approaches for achieving cell-type
      specific expression are to use a cell-type-specific promoter to control
      recombinant gene expression or to modify a virus vector particle to target gene
      transfer to a specific cell type. Targeted gene transfer to multiple peripheral
      cell types has been described, but targeted gene transfer to a specific type of
      neuron in the brain has yet to be reported. Targeted gene transfer approaches
      with Herpes Simplex Virus (HSV-1) vectors have focused on modifying glycoprotein
      C (gC) to remove the heparin binding domain and add a binding activity for a
      specific protein on the cell surface. This study was designed to develop HSV-1
      vectors that target gene transfer to cells that contain receptors for either
      glial-cell-line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic
      factor (BDNF), such as nigrostriatal neurons. We isolated chimeric gC-GDNF or
      chimeric gC-BDNF constructs, and the resulting proteins were incorporated into
      HSV-1 virus particles. We performed helper virus-free HSV-1 vector packaging in
      the presence of each chimeric protein. The resulting vector stocks supported 2.2-
      to 5.0-fold targeted gene transfer to nigrostriatal neurons in the rat brain,
      compared to vector particles that contained wild-type (wt) gC. Gene transfer to
      nigrostriatal neurons by vector particles that contained chimeric gC-BDNF was
      reduced by preincubation with an anti-BDNF antibody. Targeted gene transfer to
      neurons that contain specific neurotrophic factor receptors may benefit specific
      physiological and gene therapy studies.

PMID- 15993511
TI  - The role of thymidylate synthase and dihydropyrimidine dehydrogenase in
      resistance to 5-fluorouracil in human lung cancer cells.
AB  - The expressions of thymidylate synthase (TS) and intracellular metabolic enzymes
      have been reported to be associated with the sensitivity and/or resistance to 5
      fluorouracil (5-FU). However, since the role of these enzymes in the mechanism of
      resistance to 5-FU has not been fully examined in lung cancer, in the present
      study we measured the expression levels of TS, dihydropyrimidine dehydrogenase
      (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT)
      genes in lung cancer cell lines by real-time PCR, and the sensitivity to 5-FU
      using the MTS assay. The expression of DPD was significantly correlated with the
      concentration of 5-FU for 50% cell survival in 15 non-small-cell lung cancer
      (NSCLC) cell lines (p<0.05), but the expressions of TS, TP, and OPRT were not.
      Treatment with 5-chloro-2,4-dihydroxypyridine, an inhibitor of DPD, altered the
      sensitivity to 5-FU in DPD-expressing RERF-LC-MT cells, indicating that
      modulation of DPD activity could increase the 5-FU sensitivity in lung cancer. In
      contrast, TS expression was dramatically higher in a 5-FU-resistant small-cell
      lung cancer cell line than in the parent cell line, whereas the expressions of
      DPD, TP, and OPRT genes were not markedly different. In order to examine the
      effect of other cytotoxic agents on TS and DPD expression, we compared the
      expressions of both genes between cisplatin-, paclitaxel-, gemcitabine-, or 7
      ethyl-10-hydroxycamptothecin-resistant lung cancer cells and their respective
      parent cells, but found no differences between any pair of resistant subline and
      the corresponding parent cell line. Our results indicate that degradation of 5-FU
      due to DPD is an important determinant in 5-FU sensitivity, while induction of TS
      contributes to acquired resistance against 5-FU in lung cancer. Therefore, the
      expression levels of TS and DPD genes may be useful indicators of 5-FU activity
      in lung cancer.

PMID- 15993512
TI  - The melanocortin-1 receptor carboxyl terminal pentapeptide is essential for MC1R
      function and expression on the cell surface.
AB  - The pigmentary actions of the melanocortins are mediated by the melanocortin-1
      receptor (MC1R), a seven transmembrane domains receptor positively coupled to Gs
      and the cAMP cascade. In order to define the structure-function relationships of
      potentially relevant domains in MC1R, particularly its C-terminal cytosolic tail,
      we generated and analyzed several variants with C-terminal deletions, as well as
      point mutants in selected residues of the human MC1R. We show that the MC1R C
      terminal pentapeptide is essential for proper receptor expression on the plasma
      membrane, and that residues Thr314, Cys315 and Trp317 are at least partially
      responsible for this effect.

PMID- 15993513
TI  - Structure-activity relationship of linear tetrapeptides Tic-DPhe-Arg-Trp-NH2 at
      the human melanocortin-4 receptor and effects on feeding behaviors in rat.
AB  - The melanocortin subtype-4 receptor (MC4R) has been implicated in the control of
      feeding behavior and body weight regulation. A series of tetrapeptides, based on
      Tic-DPhe-Arg-Trp-NH2-a mimic of the putative message sequence "His-Phe-Arg-Trp"
      and modified at the DPhe position, were prepared and pharmacologically
      characterized for potency and selectivity. Substitution of His with Tic gave
      peptides with significant increases in selectivity. The effects of the
      substitution pattern of DPhe were investigated and it has significant influences
      on potency and the level of the maximum cAMP accumulation.
      Intracerebroventricular administration of peptide 10 induced significant
      inhibition of cumulative overnight food intake and feeding duration in rats.

PMID- 15993514
TI  - Serotonergic pathways converge upon central melanocortin systems to regulate
      energy balance.
AB  - Multiple lines of research provide compelling support for an important role for
      central serotonergic (5-hydroxytryptamine, 5-HT) and melanocortin pathways in the
      regulation of food intake and body weight. In this brief review, we outline data
      supporting a model in which serotonergic pathways affect energy balance, in part,
      by converging upon central melanocortin systems to stimulate the release of the
      endogenous melanocortin agonist, alpha-melanocyte stimulating hormone (alpha
      MSH). Further, we review the neuroanatomical mapping of a downstream target of
      alpha-MSH, the melanocortin 4 receptor (MC4R), in the rodent brain. We propose
      that downstream activation of MC4R-expressing neurons substantially contributes
      to serotonin's effects on energy homeostasis.

PMID- 15993515
TI  - Activity changes and marked stereotypic behavior precede Abeta pathology in
      TgCRND8 Alzheimer mice.
AB  - Alzheimer's disease (AD) is not only characterized by cognitive decline and
      neuropathological changes, but also by non-cognitive behavioral symptoms like
      restlessness, sleep disturbance, and wandering. These symptoms are categorized in
      the "Behavioral and Psychological Symptoms of Dementia" (BPSD). We investigated
      transgenic and wildtype mice of an APP transgenic mouse model of AD (TgCRND8)
      with respect to 24 h activity and spontaneous home cage behavior at 30, 60, 90
      and 120 days of age. At all test days, transgenic and wildtype animals differed
      significantly with respect to activity patterns. In addition, activity rhythms
      changed distinctly in transgenic mice with increasing age. Transgenic mice also
      clearly showed more stereotypic behavior, which correlated significantly at 90
      and 120 days of age with elevated corticosterone metabolite concentrations in
      fecal samples. Activity patterns in TgCRND8 mice resemble altered rhythms of
      activity in AD patients. Stereotypic behaviors may be caused by the same
      mechanisms as non-cognitive behavioral symptoms of AD. Thus, it is likely that
      analogies to BPSD that precede Abeta pathology are found in APP-overexpressing
      TgCRND8 mice.

PMID- 15993516
TI  - A comparison of nurse teachers' and student nurses' attitudes toward hospitalised
      older adults.
AB  - Studies have demonstrated that gerontological content can have a positive effect
      on student nurses' attitudes toward older adults. However, few studies have
      attempted to investigate nurse teachers' attitudes toward older people. Yet
      authors acknowledge the importance of both clinical nurses and teachers in the
      socialisation process. The aim of this study is to compare the attitudes of
      student nurses with those of nurse teachers toward working with hospitalised
      older adults. A questionnaire was developed, piloted and refined until the final
      outcome was a 20 item questionnaire. The questionnaire was distributed to nurse
      teachers (n=59); first year student nurses who had completed their first term of
      theory (n=82); student nurses who had completed a theory and a clinical placement
      (n=80). Statistical analysis of the data included ANOVA with a post hoc
      comparison. Results indicated that nurse teachers were most positive for a number
      of items on the questionnaire. However, they were least positive about their role
      in promoting an interest in older people and keeping up to date about advances in
      the field of older people. It is the responsibility of both teachers and clinical
      staff to dispel stereotypes that student nurses bring in to nursing.

PMID- 15993517
TI  - An epidemiological evaluation of the prevalence of malnutrition in Spanish
      patients with locally advanced or metastatic cancer.
AB  - OBJECTIVE: Malnutrition is frequent in cancer. The objective of this study was to
      determine the prevalence, in Spain, of malnutrition in cancer patients with
      advanced disease and to assess the therapeutic focus. METHODS: A total of 781
      patients were evaluated to determine individual nutritional status using the
      Scored Patient Generated-Subjective Global Assessment (Scored PG-SGA)
      questionnaire. Almost 60% of the patients included were receiving cancer
      treatment. RESULTS: Patients with the highest weight loss were those with tumours
      of oesophagus (57%), stomach (50%) and larynx (47%). Serious eating problems were
      encountered by 68% of the patients; the principal problem being anorexia (42.2%).
      The median number of symptoms impeding food intake was 2. According to the Scored
      PG-SGA, 52% of the patients were moderately or severely malnourished and 97.6%
      required some form of nutritional intervention/recommendation. CONCLUSIONS: (a)
      the majority of patients in the study needed nutritional intervention; (b) more
      than 50% had moderate or severe malnutrition; (c) the Scored PG-SGA is a useful
      and simple tool for evaluating nutritional status and contains additional
      information on nutritional recommendations; (d) nutritional evaluation of the
      cancer patients needs to be improved so as to offer better treatment of symptoms
      and to improve the patient's quality of life.

PMID- 15993519
TI  - Use of apical root elevator for compressive anaesthesia during local anaesthesia
      of the palate.

PMID- 15993518
TI  - A recombinant live attenuated measles vaccine vector primes effective HLA-A0201
      restricted cytotoxic T lymphocytes and broadly neutralizing antibodies against
      HIV-1 conserved epitopes.
AB  - Live attenuated measles vaccine (MV) could provide a safe and efficient pediatric
      vaccination vector to immunize children simultaneously against measles and human
      immunodeficiency virus type 1 (HIV-1). To evaluate the capacity of a vector
      derived from the certified Schwarz measles vaccine (MVSchw) to prime effective
      cytotoxic T cells (CTL) and broad neutralizing antibodies against HIV-1 conserved
      epitopes, we generated recombinant MVSchw viruses expressing HIV-1 antigens. We
      demonstrate that a recombinant MVSchw virus expressing an HIV-1-derived CTL
      polyepitope primes effective HLA-A0201-restricted CTLs against multiple conserved
      HIV-1 epitopes in mice susceptible to measles and humanized for the major
      histocompatibility complex (MHC) class-I molecule HLA-A0201. Additionally, we
      show that a recombinant MVSchw virus expressing an HIV-1(89.6) gp140 glycoprotein
      whose hyper variable V1, V2 and V3 loops were deleted (DeltaV1V2V3gp140), induces
      broadly neutralizing antibodies against HIV-1 primary isolates. These results
      show that the MVSchw pediatric vaccination vector induces efficient cellular and
      humoral HIV-specific immune responses.

PMID- 15993520
TI  - Fast-track referrals for oral lesions: a prospective study.
AB  - Since the introduction of the 14-day rule for referrals for cancer in 1999 there
      has been some suspicion that rates of detection of cancer are low and the number
      of inappropriate referrals is high. We undertook a prospective study of 150
      consecutive patients with oral lesions referred to a department of oral and
      maxillofacial surgery in a teaching hospital that uses a "two week wait" fast
      track referral system for head and neck cancers. The main outcome measures were
      the number of cancers detected, the age and sex of the patients, the number seen
      within 2 weeks, by whom, and the final diagnosis. Most patients (n=120, 80%) were
      referred with oral ulceration. All patients were seen within 2 weeks (mean 6
      days). Nine patients (6%) had a diagnosis of malignancy and 17 (11%) had no
      detectable abnormality. The study confirms what others have shown, that the yield
      of diagnoses of malignant disease from fast-track referrals is low and the number
      of non-urgent referrals is high.

PMID- 15993521
TI  - Head and neck cancer, England, UK-action is getting faster, have you not noticed?

PMID- 15993522
TI  - Traction radiography for the diagnosis of scapholunate ligament tears.
AB  - The diagnosis of scapholunate ligament injury by traction radiography was
      investigated within a consecutive study. The right wrists of 25 healthy
      volunteers and 22 wrists with arthroscopically proven complete scapholunate
      ligament tears were examined. Traction radiography was performed under
      fluoroscopy with a force of 5 kg applied to the thumb. In the normal wrists, this
      led to selective widening of the scapholunate joint space whereas the
      lunotriquetral distance remained unchanged. In 25 healthy right wrists, the
      median scapholunate distance measured 2.1 (range 1.3-2.6) mm on resting
      radiographs and 2.2 (range 1.7-3.5) mm on the stress radiographs. For the 22
      wrists with complete scapholunate ligament tears, the median scapholunate
      distance was increased from 2.0 (range 1.0-3.0) mm to 3.8 (range 3.0-5.5) mm by
      traction (median difference of 1.8 (range 1.0-3.0) mm). In conclusion, a
      scapholunate distance of 3.0 mm or more in unloaded wrists or widening of the
      scapholunate interval by 1.0 mm or more under thumb traction should both be
      considered as pathological findings. We recommend traction radiography as a
      simple and valuable diagnostic procedure for suspected scapholunate ligament
      injury.

PMID- 15993523
TI  - Pin arthrodesis of the wrist--a modified technique.
AB  - An intramedullary pin is commonly used for wrist arthrodesis in patients with
      rheumatoid arthritis. However, pin migration is a recognized complication of this
      technique. We report the results of wrist fusion in 15 patients using a modified
      technique with a transverse blocking screw inserted into the metacarpal distal to
      the intramedullary pin to prevent distal migration and backing out of the
      intramedullary pin. The procedure is simple to perform, does not add
      significantly to the operating time and has not been associated with any
      complications.

PMID- 15993524
TI  - Dupuytren's disease in France--1831 to 2001--from description to economic burden.
AB  - We recorded all elective admissions for Dupuytren's disease from the French
      National Hospital Database. We used the data from first hospitalizations to
      calculate the 2001 hospitalization rates for this condition and determine
      geographical differences between different regions of France. We also calculated
      the hospital costs of treating admissions with this disease. Fourteen thousand
      eight hundred and sixty hospitalizations for Dupuytren's disease were reported in
      France in 2001, of which 93% were for a first treatment. The disease was mostly
      present in men and was mostly managed by surgical fasciectomy. Most operations
      were carried out in private hospitals, with a mean stay of 2 days. Geographical
      differences were found in men only. The total hospital cost for all elective
      admissions was 14, 179, 998 Euros, indicating the considerable financial burden
      to the State of treating this condition.

PMID- 15993525
TI  - Posteroanterior stiffness predicts sagittal plane midthoracic range of motion and
      three-dimensional flexibility in cadaveric spine segments.
AB  - BACKGROUND: Spinal joint mobilization is a mainstay of clinical assessment of
      individuals with back pain. The clinician manually assesses stiffness and joint
      motion relative to segments above and below. Although clinical theory suggests
      that manually performed techniques can predict or detect intervertebral motion,
      this hypothesis remains untested. METHODS: Using a precision opto-electronic
      camera system and a custom spine testing machine, we measured intervertebral
      range of motion, neutral zone motion and three-dimensional flexibility in eight
      T5-T8 cadaveric specimens (mean age=81 years). We then measured stiffness when a
      cyclic posteroanterior load was applied at the spinous process of T6 using a
      servohydraulic material testing machine (Instron 8874), simulating the
      posteroanterior spinal mobilization technique. FINDINGs. There was a strong
      significant inverse relationship between stiffness during cyclic posteroanterior
      loading of T6 and flexion or extension range of motion of T6 relative to T7 (r=
      0.88, P<0.01, extension; r=-0.81, P=0.01, flexion), and T6-T7 flexibility in all
      six directions. INTERPRETATION: Stiffness during simulated central cyclic
      posteroanterior mobilization in the cadaveric midthoracic spine is inversely
      correlated with flexion and extension range of motion and three-dimensional
      flexibility at the level at which the technique is applied. These findings
      provide biomechanical support for the inclusion of specific joint mobilization in
      the assessment of older adults with back pain.

PMID- 15993526
TI  - Tetrodotoxin prevents copper-induced bradycardia in gastropod limpets.
AB  - Acute exposure to waterborne copper is followed by a reduction in heart rate in
      gastropod limpets. In order to understand the mechanism of this effect, exposure
      to copper (0.25 or 0.5 mg l(-1); for 3 and 6 h) was combined with an injection of
      tetrodotoxin (TTX, 20 microl, 0.5 or 1 microM), a natural toxin that inhibits the
      propagation and transmission of impulses in excitable tissues. Experiments were
      performed on the Mediterranean limpet Patella caerulea, using a non-invasive
      method for the recording of cardiac activity. TTX did not affect the bradycardic
      effect of the cholinergic agonist carbachol. However, this toxin significantly
      antagonized the bradycardia induced by 0.25 and 0.5mg l(-1) of copper exposure
      and prevented the acardia observed in some limpets exposed to 0.5mg l(-1) of
      copper for 6h. These results are consistent with the hypothesis that the
      inhibitory action of copper on limpet cardiac activity involves an extrinsic,
      cholinergic neuronal control.

PMID- 15993527
TI  - Assessment of the ecological potential of mine-water treatment wetlands using a
      baseline survey of macroinvertebrate communities.
AB  - A baseline survey of macroinvertebrate populations in two mine-water treatment
      wetlands, one treating a net acidic spoil heap discharge and one a net alkaline
      ferruginous pumped mine water, was undertaken to assess the potential of these
      systems to provide habitats for faunal communities. Both wetlands were found to
      be impoverished in comparison to natural wetlands but did sustain a
      macroinvertebrate community that could support higher organisms. Wetland size and
      water quality in terms of pH, conductivity and metal concentrations were found to
      be important factors in determining the quality of the populations supported.
      Direct toxicity to organisms was unlikely to be the main cause of lower
      diversity, but the smothering of organisms via the precipitation of iron
      hydroxides particularly in the early parts of the treatment systems affected
      macroinvertebrate communities. The presence of areas of open water within the
      planted systems was found to be important for providing habitats for
      macroinvertebrates and this should be both a future design and maintenance
      consideration for environmental managers.

PMID- 15993528
TI  - Bioconcentration of atrazine and chlorophenols into roots and shoots of rice
      seedlings.
AB  - Accumulation of o-chlorophenol (CP), 2,4-dichlorophenol (DCP), and atrazine
      (ATR), as single and mixed contaminants, from hydroponic solutions into roots and
      shoots of rice seedlings was studied following 48-h exposure of the plant roots.
      As single contaminants at low levels, the observed bioconcentration factors
      (BCFs) of CP and DCP with roots approximated the equilibrium values according to
      the partition-limited model. The BCF of atrazine with roots was about half the
      partition limit for unknown reasons. The BCFs of CP and ATR with shoots also
      approximated the partition limits, while the BCF for more lipophilic DCP with
      shoots was about half the estimated limit, due to insufficient water transport
      into plants for DCP. As mixed contaminants at low levels, the BCFs with both
      roots and shoots were comparable with those for the single contaminants; at high
      levels, the BCFs generally decreased because of the enhanced mixed-contaminant
      phytotoxicity, as manifested by the greatly reduced plant transpiration rate.

PMID- 15993529
TI  - Patients, consumers and survivors: a case study of mental health service user
      discourses.
AB  - This paper is an exploratory study of ways of talking about mental health.
      Drawing upon data collected from mental health service users in the Republic of
      Ireland, it employs discourse analysis within a case study approach to embellish
      three 'types' of service user identified in the sociology literature. Rather than
      being seen as specific types it is proposed that patient, consumer and survivor
      be regarded as a discursive typology which function as discursive resources for
      service users. The re-conceptualisation of these types, as discourses, allows the
      researcher to gain thicker descriptions of the ways in which service users
      socially construct their own perspectives on mental illness. Through a process of
      discourse analysis, discourses of patients, consumers and survivors are
      extrapolated out from interview talk with members of mental health social
      movement organisations or groups. The identified discourses contain intrinsically
      different ways of talking about mental illness and allude to different
      conceptions of agency on the part of the service user. It is argued that they
      offer an insight into bottom-up social constructions of mental illness. It is
      proposed that these discourses suggest that notions of patients, consumers and
      survivors have entered the service users' discursive canon and that they are
      actively utilised by service users to socially construct their perspectives on
      mental health.

PMID- 15993530
TI  - Patients' and healthcare providers' understandings of life-sustaining treatment:
      are perceptions of goals shared or divergent?
AB  - In this cross-sectional qualitative study, researchers performed in-depth,
      semistructured interviews with 30 pairs of patients and their primary care
      providers in an outpatient clinic of a large, urban Veterans Affairs (VA) medical
      center in the United States. During audiotaped interviews to assess their
      understanding of advance directive concepts, participants were asked what "life
      sustaining treatment" means to them and why they think of it in the way they do.
      The findings indicate that patients and providers in the United States tend to
      view and discuss life-sustaining treatment in terms of four goals for end-of-life
      care: (1) extending the length of life, (2) improving the quality of life, (3)
      maintaining or improving specific biological functions, and (4) assisting the
      body for a temporary period of time. Patients thought providers were more
      concerned with extending the length of life than with quality-based outcomes, and
      patients often discussed life-sustaining treatment as acceptable means for short
      term but not long-term use. Many providers indicated that they struggle with
      conflicting quality-based and physiologic care goals. The findings highlight the
      importance of eliciting patient preferences not only for specific types of
      treatment, such as cardiopulmonary resuscitation, but also for end-of-life care
      goals or desired health-related outcomes, such as maximizing the quantity of
      life. The findings also suggest that advance directives and patient-provider
      discussions that focus on acceptable health states and valued life activities may
      be better suited to patients' end-of-life care goals than those that focus on
      specific medical interventions.

PMID- 15993531
TI  - Studying physician effects on patient outcomes: physician interactional style and
      performance on quality of care indicators.
AB  - Many prior studies which suggest a relationship between physician interactional
      style and patient outcomes may have been confounded by relying solely on patient
      reports, examining very few patients per physician, or not demonstrating evidence
      of a physician effect on the outcomes. We examined whether physician
      interactional style, measured both by patient report and objective encounter
      ratings, is related to performance on quality of care indicators. We also tested
      for the presence of physician effects on the performance indicators. Using data
      on 100 US primary care physician (PCP) claims data on 1,21,606 of their managed
      care patients, survey data on 4746 of their visiting patients, and audiotaped
      encounters of 2 standardized patients with each physician, we examined the
      relationships between claims-based quality of care indicators and both survey
      derived patient perceptions of their physicians and objective ratings of
      interactional style in the audiotaped standardized patient encounters. Multi
      level models examined whether physician effects (variance components) on care
      indicators were mediated by patient perceptions or objective ratings of
      interactional style. We found significant physician effects associated with
      glycohemoglobin and cholesterol testing. There was also a clinically significant
      association between better patient perceptions of their physicians and more
      glycohemoglobin testing. Multi-level analyses revealed, however, that the
      physician effect on glycohemoglobin testing was not mediated by patient perceived
      physician interaction style. In conclusion, similar to prior studies, we found
      evidence of an apparent relationship between patient perceptions of their
      physician and patient outcomes. However, the apparent relationships found in this
      study between patient perceptions of their physicians and patient care processes
      do not reflect physician style, but presumably reflect unmeasured patient
      confounding. Multi-level modeling may contribute to better understanding of the
      relationships between physician style and patient outcomes.

PMID- 15993532
TI  - Remember - treat the patient not the ECG!

PMID- 15993533
TI  - The shadow price of substitutable sulfur in the US electric power plant: a
      distance function approach.
AB  - Given restrictions on sulfur dioxide emissions, a feasible long-run response
      could involve either an investment in improving boiler fuel-efficiency or a shift
      to a production process that is effective in removing sulfur dioxide. To allow
      for the possibility of substitution between sulfur and productive capital, we
      measure the shadow price of sulfur dioxide as the opportunity cost of lowering
      sulfur emissions in terms of forgone capital. The input distance function is
      estimated with data from 51 coal-fired US power units operating between 1977 and
      1986. The indirect Morishima elasticities of substitution indicate that the
      substitutability of capital for sulfur is relatively high. The overall weighted
      average estimate of the shadow price of sulfur is -0.076 dollars per pound in
      constant 1976 dollars.

PMID- 15993534
TI  - Equilibrium and kinetic studies on biosorption of Hg(II), Cd(II) and Pb(II) ions
      onto microalgae Chlamydomonas reinhardtii.
AB  - The microalgae Chlamydomonas reinhardtii was used for the biosorption of Hg(II),
      Cd(II) and Pb(II) ions. The maximum adsorption of Hg(II) and Cd(II) ions on
      Chlamydomonas reinhardtii biomass was observed at pH 6.0 and the corresponding
      value for Pb(II) ions was 5.0. The biosorption of Hg(II), Cd(II) and Pb(II) ions
      by microalgae biomass increased as the initial concentration of Hg(II), Cd(II)
      and Pb(II) ions increased in the biosorption medium. The maximum biosorption
      capacities of microalgae for Hg(II), Cd(II) and Pb(II) ions were 72.2+/-0.67,
      42.6+/-0.54 and 96.3+/-0.86 mg/g dry biomass, respectively. The affinity order
      for algal biomass was Pb(II)>Hg(II)>Cd(II). FT-IR analysis of algal biomass
      revealed the presence of amino, carboxyl, hydroxyl and carbonyl groups, which
      were responsible for biosorption of metal ions. Biosorption equilibrium was
      established in about 60 min and the equilibrium was well described by the
      Freundlich biosorption isotherms. Temperature change in the range of 5-35 degrees
      C did not affect the biosorption capacity. The microalgae could be regenerated
      using 0.1 M HCl, with up to 98% recovery, which allowed the reuse of the biomass
      in six biosorption-desorption cycles without any considerable loss of biosorption
      capacity.

PMID- 15993535
TI  - Clinical significance of nuclear expression of spleen tyrosine kinase (Syk) in
      gastric cancer.
AB  - Spleen tyrosine kinase (Syk) expression was immunohistochemically examined in 250
      gastric cancer patients. The rate of positive Syk expression was 42.4%. Syk
      expression was significantly associated with T1 tumors, lymphatic invasion,
      venous invasion and lymph node metastasis (P<0.0001). The 5-year survival rate
      was significantly higher among patients with nuclear Syk expression than among
      those who were negative for Syk expression (P=0.0003). However, Syk expression
      was not an independent prognostic factor. Loss of Syk expression was closely
      related to the malignant property of gastric cancer in the context of tumor depth
      and lymph node metastasis, especially in early gastric cancer.

PMID- 15993536
TI  - Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion.
AB  - Sulforaphane (SF), a natural product from broccoli, is known to enhance
      detoxification of carcinogens and block initiation of chemically-induced
      carcinogenesis in animal models. Cell culture and xenograft studies suggest
      additional roles for SF, inhibiting growth of tumors, arresting the cell cycle
      and enhancing apoptosis. As currently reported, topical SF (1, 5 or 10
      micromol/mouse) significantly inhibited 7,12-dimethylbenz(a)anthracene/12-O
      tetradecanoylphorbol 13-acetate (TPA)-induced mouse skin tumorigenesis, using
      either an anti-promotion protocol (SF from 1 week after carcinogen until the end
      of the study) or a combined anti-initiation, anti-promotion protocol (SF 7 days
      prior to carcinogen until the end of the study). Surprisingly, no significant
      effect was observed in an anti-initiation protocol (SF from 7 days prior to 7
      days after carcinogen). Separately, SF inhibited TPA-induced ornithine
      decarboxylase activity in mouse skin, an obligate step in TPA-induced promotion
      of carcinogenesis. These data link this molecular mechanism to SF-dependent
      inhibition of the promotion of tumorigenesis.

PMID- 15993537
TI  - Age-differential patterns of brain activation during perception of angry faces.
AB  - Functional magnetic resonance imaging (fMRI) was used to study age-related
      differences in the neural circuitry involved in perception of negative facial
      affect. During scanning, 24 younger and 22 older adults viewed blocks of angry
      and neutral faces. The fMRI data analysis of the angry versus neutral faces
      contrast demonstrated greater activation in younger versus older individuals in
      the right amygdala/hippocampus region, whereas older adults demonstrated greater
      activation in the right anterior-ventral insula cortex. Hence, normal aging seems
      to affect specific nodes in the neural network involved in processing negative
      emotional face information. This age-related change from more subcortical to more
      cortical involvement could reflect functional compensation within the neural
      system involved in perception of facial affect, or the fact that older adults
      process emotional information in a different manner than do young adults.

PMID- 15993538
TI  - Increased glutathione levels in cortical and striatal mitochondria of the R6/2
      Huntington's disease mouse model.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disease
      characterized by a severe neuronal loss that occurs primarily in the neostriatum.
      It has been postulated that mitochondria dysfunction and oxidative stress may
      play significant roles in the etiology of the disease. Indeed, markers of
      oxidative stress damage have been detected in the brains of HD patients and in
      mouse models of HD. In this study, we evaluate the changes in the levels of the
      potent, endogenous antioxidant glutathione and enzymes involved in its metabolism
      or recycling in the cortex and striatum of an extensively studied HD mouse model
      (R6/2). In both cortex and striatum, the levels of cellular glutathione were not
      significantly different in the R6/2 mice when compared with littermate wild type
      controls. Remarkably, the levels of glutathione were significantly increased in
      mitochondria isolated from the cortex and striatum of R6/2 mice when compared
      with wild type control mice. This specific increase in the levels of glutathione
      in mitochondria suggests that a compensatory mechanism is induced in the R6/2
      mice to protect against an increase in oxidative stress in mitochondria.

PMID- 15993539
TI  - Immunohistochemical study of the hnRNP A2 and B1 in the hippocampal formations of
      brains with Alzheimer's disease.
AB  - To elucidate the post-transcriptional regulation in the subjects with Alzheimer's
      disease (AD), we employed immunohistochemical techniques and examined the
      expression of the heterogeneous nuclear ribonucleoprotein (hnRNP) A2 and B1 in
      the hippocampus with neurofibrillary tangle (NFT) neuropathology. In the mildly
      affected subjects (Braak stages I and II), the most intense A2 immunoreactivity
      was observed in the CA3 to CA1 neurons. In the moderately (Braak stages III and
      IV) and severely affected subjects (Braak stages V and VI), the CA1 region
      demonstrated a decrease in the number of A2 immunoreactive neurons and in
      immunoreactivity in the remaining neurons, while within the CA4 to CA2 in the
      severely affected subjects, the majority of neurons showed increased A2
      immunoreactivity. An intense B1 immunoreactivity was observed throughout the CA
      subfields. In the CA1 subfield of the moderately affected subjects and in the
      extensive hippocampal regions of the severely affected subjects, a decrease in B1
      immunoreactivity was observed. Double-immunolabeling studies demonstrated that
      tangle-bearing neurons reduced A2 and B1 immunoreactivity. Our study suggests
      that hnRNP A2 and B1 display different responses in the AD hippocampus, and
      further suggests that the post-transcriptional regulation is disturbed in neurons
      of the AD hippocampus.

PMID- 15993540
TI  - Trichinella nativa in a black bear from Plymouth, New Hampshire.
AB  - A suspected case of trichinellosis was identified in a single patient by the New
      Hampshire Public Health Laboratories in Concord, NH. The patient was thought to
      have become infected by consumption of muscle larvae (ML) in undercooked meat
      from a black bear killed in Plymouth, NH in October 2003 and stored frozen at -20
      degrees C fro 4 months. In January 2004, a 600 g sample of the meat was thawed at
      4 degrees C, digested in hydrochloric acid and pepsin, and larvae were collected
      by sedimentation. Intact, coiled, and motile ML were recovered (366 larvae per
      gram (l pg) of tissue), which were passed into mice and pigs. Multiplex PCR
      revealed a single 127 bp amplicon, indicative of Trichinella nativa. The
      Reproductive Capacity Index (RCI) for the T. nativa-Plymouth isolate in mice was
      24.3. Worm burdens in the diaphragms of two 3-month-old pigs given 2,500 ML were
      0.05 and 0.2l pg by 35 days post-inoculation, while 2.2 and 0.75 l pg were
      recovered from two 3-month-old pigs given 10,000 ML; no larvae were recovered
      from four 1-year-old pigs given 2,500 ML (n=2) or 10,000 ML (n=2). Viable larvae
      were also recovered from frozen black bear meat harvested at two additional
      locations, one in southern Ontario, Canada, and one in upstate New York, USA.
      Multiplex PCR using genomic DNA from these parasite samples demonstrated that
      both isolates were T. nativa. This is the first report of the freeze-resistant
      species, T. nativa, within the continental United States.

PMID- 15993541
TI  - A program to accredit laboratories for reliable testing of pork and horse meat
      for Trichinella.
AB  - The Canadian Food Inspection Agency (CFIA) has developed a program to accredit
      external laboratories to conduct Trichinella digestion assays for export
      purposes. Accredited laboratories are responsible for staffing, equipment and
      operating test facilities under the auspices and guidance of the CFIA. The CFIA's
      Centre for Animal Parasitology provides training, proficiency samples, audits and
      other support for the accreditation process. The program has also been adapted
      for use in laboratories conducting Trichinella digestion tests for surveillance
      and food safety purposes and provides a useful template for others wishing to
      develop similar systems.

PMID- 15993542
TI  - Expressed sequence tags from life cycle stages of Trichinella spiralis:
      application to biology and parasite control.
AB  - While the approach taken to date to study Trichinella spp., involves mainly
      characterization of individual genes of interest, we initiated a genomics
      approach as an antecedent to more complete genome sequencing. Our approach
      involves use of expressed sequence tags (ESTs) obtained from three life cycle
      stages of Trichinella spiralis; adult worms (AD), mature muscle larvae (ML) and
      immature L1 larvae (immL1, also known as newborn larvae) () to improve the
      technical capacity for research on Trichinella spp. and to generate information
      that will aid prospective development of relevant hypotheses. In this review, we
      will summarize findings of our EST analysis and discuss how they relate to topics
      mentioned above. The foundation laid by this data will also contribute toward
      development of a more substantial genomic database and technical capacity to
      dissect molecular interactions between vertebrate hosts and Trichinella spp.

PMID- 15993543
TI  - The need for implementation of International Commission on Trichinellosis
      recommendations, quality assurance standards, and proficiency sample programs in
      meat inspection for trichinellosis in Serbia.
AB  - Implementation of methods to control inspection for Trichinella in meat
      recommended by International Commission on Trichinellosis (ICT), particularly the
      introduction of the quality assurance standards and proficiency panels for
      certified analysts is extremely important in Serbia and other countries where
      Trichinellosis is endemic. In spite of existing regulations, including the
      inspection of 0.5 g samples of diaphragm by the compression method or by
      artificial digestion of 1g samples, in Serbia 280 people were diagnosed with
      clinical trichinellosis after consumption of inspected meat during the period
      2001--2002. These outbreaks, which occurred in the municipalities of Kumane,
      Surcin and Bogatic, were a consequence of inadequate application of inspection
      methods and insufficient education of some veterinary inspectors. The problem of
      inadequate veterinary inspection in Serbia can be overcome by strict application
      of the ICT recommendations for the control of Trichinella with specific emphasis
      on implementing the quality assurance system (QAS) and proficiency sampling (PS/-
      PP/panel).

PMID- 15993544
TI  - Evaluation of ELISA for detection of Trichinella antibodies in muscle juice
      samples of naturally infected pigs.
AB  - The performance characteristics of an ELISA test for trichinellosis in pigs
      applied to muscle juice was assessed using 314 samples collected from pigs
      located in endemic areas of Croatia. Peptic digestion was used as the reference
      method. The diagnostic accuracy of the two compared dilutions (1:10 and 1:100)
      was considered to be high because the area under the curve (AUC) index was 0.922
      and 0.920 for each dilution, respectively. In this study the two graph-receiver
      operating characteristic (TG-ROC) analysis was used as a tool for selecting cut
      off points. Sensitivity, specificity, likelihood ratios, efficiency and Youden's
      index were used as indices of test accuracy. The cut-off values that minimize
      overall misclassification cost under an assumption of 3% prevalence were
      calculated. Our results indicate that the ELISA applied to muscle juice is a
      highly accurate test and can be adapted to process a large number of samples.

PMID- 15993545
TI  - Psychometric properties of the 'Processes of Change' scale for alcohol misuse and
      its short form (POC-20).
AB  - Regarding the processes of change, one of the core constructs of the
      transtheoretical model of intentional behavior change (TTM), extensive research
      has been done in the field of smoking. However, little is known about the
      processes of change for alcohol misuse and their measurement. This study's goals
      were to investigate the psychometric properties of the German Processes of Change
      (POC) scale and to refine a short version. METHOD: A sample of 653 non-treatment
      seeking general hospital patients with alcohol problems was used. Construct
      validity of the POC was analyzed using confirmatory factor analysis. As another
      validity aspect the use of processes of change across the stages of change was
      investigated. RESULTS: Internal consistency of the POC-20 ranged between r=.57
      and .94. Construct validity was also good (CFI=.94). In line with TTM postulates
      subjects in later stages reported more behavioral processes compared to
      individuals in earlier stages. CONCLUSION: Findings indicated superiority of the
      POC-20 over the long version and good validity of the measure in a high per
      capita consumption nation.

PMID- 15993546
TI  - Nicotine dependence, motivation to quit, and diagnosis in emergency department
      patients who smoke.
AB  - OBJECTIVES: To assess the effect of diagnosis on motivation to quit in adult
      smokers in an emergency department (ED). METHODS: A survey of patients visiting
      two EDs from September to November, 2003. Patients screening positive for smoking
      completed a Fagerstrom Test for Nicotine Dependence and Ladder of Contemplation.
      ICD9 codes and disposition status were recorded. Smoking-related diagnoses were
      drawn from standard sources. Data were analyzed with parametric and non
      parametric statistics. RESULTS: Five hundred and eighty-five were interviewed,
      median age 40 (interquartile range 29-50); 323 (55%) were female. Ninety percent
      of all patients were non-White; 69% were uninsured or had Medicaid. Of 152
      patients with smoking-related diagnoses, the median Fagerstrom score was 4.7 vs.
      4.1 for patients with a non-smoking-related diagnosis (p=0.02, 95% CI for the
      difference 0.2, 0.9). Patients with smoking-related and non-smoking-related
      diagnoses had similar levels of motivation to quit (Ladder score, respectively,
      5.5 vs. 5.1, p=0.03, 95% CI for difference 0.03, 0.8). CONCLUSIONS: Adult ED
      smokers exhibit mild-moderate levels of nicotine addiction and interest in
      quitting. ED-based tobacco control should target all smokers.

PMID- 15993547
TI  - Latent chlamydial infections: the probable cause of a wide spectrum of human
      diseases.
AB  - In the decade from 1980 to 1990, anamnestic data were amassed from 746 animal
      breeders on 31 farms, suffering from similar health problems and at the same
      time, 146 people from various professions outside agriculture were chosen as a
      control sample. A randomly selected group of 20 people from the 746 animal
      breeders were serologically tested for a wide range of infectious diseases
      (mycoplasmosis, tularaemia, leptospirosis, boreliosis, toxoplasmosis,
      listeriosis, and others). The analyses of these tests showed comparable figures
      in the majority of the tested people only in their serological response to
      chlamydial infection. Then, another randomly selected group of 157 people were
      serologically tested specifically for chlamydial infection. In 96% of these
      people a serological chlamydial response to a general chlamydial antigen and
      Chlamydia trachomatis antigen were diagnosed. Over the following eight years,
      these people were under medical observation and from one to four times a year
      they were serologically tested for various chlamydial antigens. After 12 years of
      intensive research, analyses and consultations with experts in both human and
      veterinary medicine, the findings of the research showed that the cause of a
      number of health problems and diseases could be identified in latent chlamydial
      infection. These findings were published in veterinary journals in the Czech
      Republic and Germany in 1992 [Von Bazala E, Renda J. Latente
      Chlamydieninfektionen als Ursache von Gesundheitsstorungen bei Schweine-, Rinder-
      und Schafzuchtern in der CSFR. Berl. Munch. Tierarztl. Wschr. 1992;105(145-149)
      105. Heft 5. 1. Mai 1992]. Due to persistent and deteriorating health problems in
      a majority of the examined people, the research efforts were continued and
      similar symptoms were consequently discovered in people from urban, non-animal
      breeding communities, of whom most of the long-term afflicted were also in many
      cases tested Chlamydia seropositive.

PMID- 15993548
TI  - Cauda equina tolerance to high-dose fractionated irradiation.
AB  - PURPOSE: To report late neurologic toxicity rates and clinical outcomes for
      patients treated with high dose fractionated radiation therapy using three
      dimensional treatment planning and combined proton and photon beams to portions
      of the cauda equina (L2-coccyx). METHODS AND MATERIALS: Medical records of 53
      patients treated to fields encompassing the cauda equina were reviewed for the
      onset of neurologic symptoms in the absence of local failure. All doses were
      normalized to equivalent dose delivered in 2-Gy fractions. Median cauda dose was
      65.8 cobalt Gray equivalents (CGE) (range, 31.9-85.1). Median follow-up was 87
      months (range, 14-217 months). RESULTS: Nineteen patients experienced local
      recurrences, and 13 others had neurologic toxicity. A total of 54% (i.e., 7/13)
      of the toxicities occurred 5 years or more after treatment. Median caudal dose
      was 73.7 CGE in the group with neurologic toxicity, and 55.6 CGE in those
      without. On multivariate actuarial analysis, cauda dose and gender were
      statistically significant for neurotoxicity at p = 0.002 and p = 0.017,
      respectively. The estimated tolerance doses 5 years from treatment, TD 5/5 and TD
      50/5, were 55 CGE and 72 CGE, respectively, for males and 67 CGE and 84 CGE for
      females. The tolerance doses were about 8 CGE lower when estimated at 10 years
      from treatment. Disease-free survival rates at 5 and 10 years were 66% and 53%,
      respectively. CONCLUSIONS: This study suggests that the probability of
      neurotoxicity is a relatively steep function of dose to cauda equina (slope
      gamma50 = approximately 3). The cauda equina tolerance is greater for females
      than males by about 11 CGE (at 2 CGE per fraction). Extended follow-up is
      necessary to accurately assess neurologic damage and then differentiate that
      phenomenon from local recurrence; the traditional 5-year assessment has limited
      meaning in this population. Local control remains an issue for these patients,
      even with the radical doses used.

PMID- 15993549
TI  - Capecitabine and radiation therapy preceded and followed by combination
      chemotherapy in advanced pancreatic cancer.
AB  - PURPOSE: The primary objective of this study was to evaluate the tolerance and
      toxicity of radiation therapy (RT) and capecitabine in patients with advanced,
      unresectable pancreatic carcinoma. To control micrometastatic disease,
      combination chemotherapy (gemcitabine and cisplatin) before and after combined
      modality therapy (CMT) was planned. METHODS AND MATERIALS: Patients with
      unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000
      mg/m2 and cisplatin 35 mg/m2 were administered on Days 1 and 8 of a 21-day cycle
      for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions.
      Patients were treated with capecitabine 1330 mg/m2 daily during RT. After CMT,
      two additional cycles of gemcitabine and cisplatin completed the treatment.
      RESULTS: Twenty-three patients were treated. Eighteen patients completed CMT. One
      patient was removed from study during CMT for toxicity issues. Treatment delays
      and dose reductions were common during the final two cycles of gemcitabine and
      cisplatin as a result of myelosuppression. Median survival was 10.1 months (95%
      confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI
      = 8.2, 18.9) for 18 patients without metastasis. CONCLUSION: Combined modality
      therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was
      difficult to complete owing to cumulative myelosuppression. Survival, response,
      and toxicity were comparable to infusional 5-fluorouracil and RT.

PMID- 15993550
TI  - Adenoviral-E2F-1 radiosensitizes p53wild-type and p53null human prostate cancer
      cells.
AB  - PURPOSE: E2F-1 is a transcription factor that enhances the radiosensitivity of
      various cell lines by inducing apoptosis. However, there are conflicting data
      concerning whether this enhancement is mediated via p53 dependent pathways.
      Additionally, the role of E2F-1 in the response of human prostate cancer to
      radiation has not been well characterized. In this study, we investigated the
      effect of Adenoviral-E2F-1 (Ad-E2F-1) on the radiosensitivity of p53wild-type
      (LNCaP) and p53null (PC3) prostate cancer cell lines. METHODS AND MATERIALS:
      LNCaP and PC3 cells were transduced with Ad-E2F-1, Adenoviral-Luciferase (Ad-Luc)
      control vector, or Adenoviral-p53 (Ad-p53). Expression of E2F-1 and p53 was
      examined by Western blot analysis. Annexin V and caspase 3 + 7 assays were
      performed to estimate the levels of apoptosis. Clonogenic survival assays were
      used to determine overall cell death. Statistical significance was determined by
      analysis of variance, using the Bonferroni method to correct for multiple
      comparisons. RESULTS: Western blot analysis confirmed the efficacy of
      transductions with Ad-E2F-1 and Ad-p53. Ad-E2F-1 transduction significantly
      enhanced apoptosis and decreased clonogenic survival in both cell lines. These
      effects were compounded by the addition of RT. Although E2F-1-mediated
      radiosensitization was independent of p53 status, this effect was more pronounced
      in p53wild-type LNCaP cells. When PC3 cells were treated with Ad-p53 in
      combination with RT and Ad-E2F-1, there was at least an additive reduction in
      clonogenic survival. CONCLUSIONS: Our results suggest that Ad-E2F-1 significantly
      enhances the response of p53wild-type and p53null prostate cancer cells to
      radiation therapy, although radiosensitization is more pronounced in the presence
      of p53. Ad-E2F-1 may be a useful adjunct to radiation therapy in the treatment of
      prostate cancer.

PMID- 15993551
TI  - Free radical scavenging activity of Achillea alexandri-regis extracts.
AB  - The antioxidative potential of Achillea alexandri-regis has been studied by
      measuring the influence of herb extracts on hydroxyl and superoxide radicals'
      quantity in different in vitro systems. The ethyl acetate extract exhibited
      hydroxyl radical scavenging activity in all tested biological system (liver
      homogenate, hemolyzed blood, serum and postmitochondrial liver fraction), whereas
      butanol extract reduced hydroxyl radicals significantly only in the
      postmitochondrial liver fraction. Both extracts showed superoxide radical
      scavenging effect only in hemolyzed blood.

PMID- 15993552
TI  - Cycling in and out of treatment; participation in methadone treatment in NSW,
      1990-2002.
AB  - BACKGROUND: There are few descriptions of patterns of long-term participation in
      methadone treatment. There has been progressive expansion of methadone
      maintenance treatment (MMT) in Australia in the last 15 years, and by
      international standards Australia has a high participation rate in MMT, and has
      accumulated extensive data on participation. AIM: (1) To analyse predictors of
      retention in treatment (a proxy measure of treatment effectiveness) in three
      cohorts of people entering public and private methadone treatment, in 1990, 1995,
      and 2000 in the state of New South Wales (NSW), and to compare retention rates
      with those reported from recent clinical trials; and (2) to describe the pattern
      of participation in subsequent treatment and predictors of re-entry. METHOD:
      Sequential first admissions to MMT for the month of February during 1990, 1995,
      and 2000, were identified from the NSW Health database. Initial treatment setting
      (public or private) was identified. Pattern of subsequent participation in
      treatment of all subjects was also extracted. Descriptive statistics were
      generated, and predictors of retention in treatment and re-entry to treatment
      were analysed. RESULTS: The sample comprised 342 subjects commencing in private
      and 135 in public settings. Retention did not differ between settings. At 6
      months, 51% in the current study were retained, compared to 48% in pooled
      clinical trials from Australia. There was a significant cohort effect; at 3
      months retention was significantly better in the 1990 cohort, but by 12 months,
      differences between the year-cohorts were not statistically significant. Most
      people who left treatment dropped out; two-thirds subsequently re-entered MMT,
      often having multiple episodes. Participation in non-continuous treatment was
      around 45% for the 5 years after first entering treatment. Using multiple
      logistic regression, the significant predictors of re-entry to treatment were
      age, and duration of first treatment episode; specifically, older people and
      those with >12 months continuous treatment were significantly less likely to re
      enter. CONCLUSION: Retention in treatment in practice, across a range of
      settings, appears comparable to treatment delivered in clinical trials.
      Participants cycle in and out of treatment, and this recycling appears to have
      increased as the program has expanded and access to treatment has increased.

PMID- 15993553
TI  - Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic
      pathways in human oral keratinocytes and tissues.

PMID- 15993554
TI  - Ethnobotany/ethnopharmacology and mass bioprospecting: issues on intellectual
      property and benefit-sharing.
AB  - Ethnobotany/ethnopharmacology has contributed to the discovery of many important
      plant-derived drugs. Field explorations to seek and document
      indigenous/traditional medical knowledge (IMK/TMK), and/or the biodiversity with
      which the IMK/TMK is attached, and its conversion into a commercialized product
      is known as bioprospecting or biodiversity prospecting. When performed in a large
      scale operation, the effort is referred to as mass bioprospecting. Experiences
      from the mass bioprospecting efforts undertaken by the United States National
      Cancer Institute, the National Cooperative Drug Discovery Groups (NCDDG) and the
      International Cooperative Biodiversity Groups (ICBG) programs demonstrate that
      mass bioprospecting is a complex process, involving expertise from diverse areas
      of human endeavors, but central to it is the Memorandum of Agreement (MOA) that
      recognizes issues on genetic access, prior informed consent, intellectual
      property and the sharing of benefits that may arise as a result of the effort.
      Future mass bioprospecting endeavors must take heed of the lessons learned from
      past and present experiences in the planning for a successful mass bioprospecting
      venture.

PMID- 15993555
TI  - A pharmacological study on Berberis vulgaris fruit extract.
AB  - Berberis vulgaris fruit (barberry) is known for its antiarrhythmic and sedative
      effects in Iranian traditional medicine. The effects of crude aqueous extract of
      barberry on rat arterial blood pressure and the contractile responses of isolated
      rat aortic rings and mesenteric bed to phenylephrine were investigated. We also
      examined effect of the extract on potassium currents recorded from cells in
      parabrachial nucleus and cerebellum rejoins of rat brain. Administration of the
      extract (0.05-1 mg/100 g body weight of rat) significantly reduced the mean
      arterial blood pressure and heart rate in anaesthetized normotensive and
      desoxycorticosteron acetate-induced hypertensive rats in a dose-dependent manner.
      Concentration-response curves for phenylephrine effects on isolated rat aortic
      rings and the isolated mesenteric beds in the presence of the extract were
      significantly shifted to the right. Application of the extract (1-50 microg/ml)
      shifted the activation threshold voltage to more negative potentials, leading to
      an enhancement in magnitude of the outward potassium current recorded from cells
      present in rat brain slices of parabrachial nucleus and cerebellum. This effect
      on potassium current may explain the sedative and neuroprotective effects of
      barberry. The present data support the hypothesis that the aqueous extract of
      barberry has beneficial effects on both cardiovascular and neural system
      suggesting a potential use for treatment of hypertension, tachycardia and some
      neuronal disorders, such as epilepsy and convulsion.

PMID- 15993556
TI  - Recent developments in the field of arrow and dart poisons.
AB  - Arrow and dart poisons, considered as conventional natural sources for future
      drug discovery, have already provided numerous biologically active molecules used
      as drugs in therapeutic applications or in pharmacological research. Plants
      containing alkaloids or cardiotonic glycosides have generally been the main
      ingredients responsible for the efficacy of these poisons, although some animals,
      such as frogs, have also been employed. This paper, without being exhaustive,
      reports the greater strides made during the past 15 years in the understanding of
      the chemical nature and biological properties of arrow and dart poison
      constituents. Examples both of promising biological properties shown by these
      molecules and of crucial discoveries achieved by their use as pharmacological
      tools are given. Further studies of these toxic principles are likely to enable
      scientists to find new valuable lead compounds, useful in many fields of
      research, like oncology, inflammation and infectious diseases.

PMID- 15993557
TI  - Apoptosis and nitric oxide in an experimental model of osteoarthritis in rabbit
      after hyaluronic acid treatment.
AB  - OBJECTIVE: this study determine the effect of hyaluronic acid on chondrocyte
      apoptosis, as well as variations in nitric oxide levels in an experimental model
      of osteoarthritis elicited anterior cruciate ligament section (ACL) in a rabbit
      model with two differentiated developmental periods. METHODS: apoptosis and the
      quantification of nitric oxide (NO) were studied in two groups of 16 animals
      each. All animals had both knees operated, but only the right knees were treated
      with hyaluronic acid (HA). In the first group hyaluronic treatment was performed
      five weeks after osteoarthritis induction (short term group, ST) and in the
      second group, 10 weeks after induction (long term group, LT). The animals in both
      series were sacrificed two weeks after the last dose of HA. Flow cytometry by
      means of Annexin labelling and the TUNEL method were used for the study of
      apoptosis, NO levels were measured in cultured cartilage and in the supernatant
      of the enzymatic digestion of the cartilage. RESULTS: regarding apoptosis
      measurement, a significant reduction in apoptosis levels was observed in both
      series as compared to untreated knees. NO production was lower in knees treated
      with HA, with significant differences after cartilage digestion. CONCLUSION: The
      administration of HA has been effective ameliorating the damage associated with
      the process of osteoarthritis induced by experimental surgery as evidenced by
      decreased apoptosis (TUNEL method), the results more promising in the earlier
      phases of the disease.

PMID- 15993558
TI  - Implementing a computer-assisted telephone interview (CATI) system to increase
      colorectal cancer screening: a process evaluation.
AB  - OBJECTIVE: Computer-assisted telephone interviewing (CATI) systems used by
      telephone counselors (TCs) may be efficient mechanisms to counsel patients on
      cancer and recommended preventive screening tests in order to extend a primary
      care provider's reach to his/her patients. The implementation process of such a
      system for promoting colorectal (CRC) cancer screening using a computer-assisted
      telephone interview (CATI) system is reported in this paper. METHODS: The process
      evaluation assessed three components of the intervention: message production,
      program implementation and audience reception. RESULTS: Of 1181 potentially
      eligible patients, 1025 (87%) patients were reached by the TCs and 725 of those
      patients (71%) were eligible to receive counseling. Five hundred eighty-two (80%)
      patients agreed to counseling. CONCLUSIONS: It is feasible to design and use CATI
      systems for prevention counseling of patients in primary care practices. PRACTICE
      IMPLICATIONS: CATI systems have the potential of being used as a referral service
      by primary care providers and health care organizations for patient education.

PMID- 15993559
TI  - Promoting adherence to antibiotics: a test of implementation intentions.
AB  - OBJECTIVE: This prospective study tested whether implementation intentions
      increased adherence to short-term antibiotics in a patient sample. Implementation
      intentions specify exactly when and where an individual will undertake an
      activity. They may help people achieve health behaviours, such as taking
      medicines. METHODS: A total of 220 patients with an antibiotics prescription were
      randomly assigned to four groups (control, Theory of Planned Behaviour (TPB)
      questionnaire, TPB questionnaire+formed own implementation intention for taking
      the medicine, TPB questionnaire+researcher formed implementation intention).
      Participants were telephoned at the end of the course to record adherence. Two
      hundred and seven participants completed the study. RESULTS: At follow-up,
      adherence was high (75.8% reported no tablets left). Analysis revealed no
      significant difference in adherence between groups. CONCLUSION: High adherence to
      antibiotics was achieved, but not improved by implementation intentions. PRACTICE
      IMPLICATIONS: Providing information and telephone follow-up may have been the
      unintended effective intervention in this study.

PMID- 15993560
TI  - Inhibition of matrix metalloproteinase activity and growth of gastric
      adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro
      and murine models.
AB  - INTRODUCTION: Angiotensin converting enzyme (ACE) shares structural homology with
      the matrix metalloproteinase family of proteolytic enzymes (MMPs) responsible for
      degradation of the extracellular matrix (ECM). ACE inhibitors have been reported
      to protect against cancer in patients. The aim of this study was to determine
      whether the ACE inhibitor, captopril, could impair the activity of MMPs and
      impact on tumour invasion and growth in a cell line and murine model. METHODS:
      For proof of principle, the protein activity of human MMP-2 and MMP-9 produced by
      the HT1080 fibrosarcoma cell line was detected using gelatin zymography. Gene
      expression was determined by real time reverse transcriptase PCR and tumour cell
      invasion using Matrigel invasion chambers. The effect of captopril on the in vivo
      growth of MGLVA-1 human gastric adenocarcinoma xenografts was evaluated in a nude
      mouse model. RESULTS: Captopril inhibited activity of secreted MMP-9 and MMP-2,
      however, gene expression in HT1080 remained unaltered. Invasion of HT1080 cells
      was inhibited by 48% (p<0.001). Tumour size was reduced by 40-50% with 0.4 mg/ml
      captopril (p<0.01) and when combined with cisplatin the inhibition increased to
      71% (p<0.05). DISCUSSION: ACE inhibitors inhibit the activity of secreted MMP-2
      and -9 by a mechanism similar to synthetic MMP inhibitors. ACE inhibitors have
      previously been shown to inhibit tumour growth, however; this is the first study
      to demonstrate inhibition of a human gastric xenograft, both alone and in
      combination with cisplatin. These results support further investigation into the
      anticancer effects of ACE inhibitors.

PMID- 15993561
TI  - In vivo flooding for anxiety disorders: proposing its utility in the treatment
      posttraumatic stress disorder.
AB  - Exposure techniques have now been used in the treatment of anxiety disorders for
      several decades. Although such techniques are a dominant feature of current
      therapies for disorders such as posttraumatic stress disorder and acute stress
      disorder, examination of their relative merits has been less studied. The purpose
      of this review is to suggest the usefulness of in vivo flooding in the treatment
      of posttraumatic stress. We discuss the relevant exposure literature by briefly
      examining the efficacy of these techniques in the treatment of anxiety. The
      theoretical and methodological limitations of investigations to date of exposure
      methods that have been used in posttraumatic stress treatment studies are then
      reviewed. We highlight the fact that in vivo flooding, an exposure technique that
      has been used to treat some anxiety-based disorders, has received scant clinical
      and research attention as a treatment for posttraumatic stress. A case is made
      for further study of in vivo flooding in the treatment of posttraumatic stress.

PMID- 15993562
TI  - Allelic variation in gene expression identified through computational analysis of
      the dbEST database.
AB  - Differential expression between the two alleles of an individual and between
      people with different genotypes has been commonly observed. Quantitative
      differences in gene expression between people may provide the genetic basis for
      the phenotypic difference between individuals and may be the primary cause of
      complex diseases. In this paper, we developed a computational method to identify
      genes that displayed allelic variation in gene expression in human EST libraries.
      To model allele-specific gene expression, we first identified EST libraries in
      which both A and B alleles were expressed and then identified allelic variation
      in gene expression based on the EST counts for each allele using a binomial test.
      Among 1107 SNPs that had a sufficient number of ESTs for the analysis, 524 (47%)
      displayed allelic variation in at least one cDNA library. We verified
      experimentally the allelic variation in gene expression for 6 of these SNPs. The
      frequency of allelic variation observed in EST libraries was similar to the
      previous studies using the SNP chip and primer extension method. We found that
      genes that displayed allelic variation were distributed throughout the human
      genome and were enriched in certain chromosome regions. The SNPs and genes
      identified in this study will provide a rich source for evaluating the effects of
      those SNPs and associated haplotypes in human health and diseases.

PMID- 15993563
TI  - Cyto- and chemoarchitecture of the amygdala of a monotreme, Tachyglossus
      aculeatus (the short-beaked echidna).
AB  - We have examined the cyto- and chemoarchitecture of the temporal and extended
      amygdala in the brain of a monotreme (the short-beaked echidna Tachyglossus
      aculeatus) using Nissl and myelin staining, enzyme histochemistry for
      acetylcholine esterase and NADPH diaphorase, immunohistochemistry for calcium
      binding proteins (parvalbumin, calbindin and calretinin) and tyrosine
      hydroxylase. While the broad subdivisions of the eutherian temporal amygdala were
      present in the echidna brain, there were some noticeable differences. No
      immunoreactivity for parvalbumin or calretinin for somata was found in the
      temporal amygdala of the echidna. The nucleus of the lateral olfactory tract
      could not be definitively identified and the medial nucleus of amygdala appeared
      to be very small in the echidna. Calbindin immunoreactive neurons were most
      frequently found in the ventrolateral part of the lateral nucleus,
      intraamygdaloid parts of the bed nucleus of the stria terminalis and the lateral
      part of the central nucleus. Neurons strongly reactive for NADPH diaphorase with
      filling of the dendritic tree were found mainly scattered through the cortical,
      central and lateral subnuclei, while neurons showing only somata reactivity for
      NADPH diaphorase were concentrated in the basomedial and basolateral subnuclei.
      Most of the components of the extended amygdala of eutherians could also be
      identified in the echidna. Volumetric analysis indicated that the temporal
      amygdala in both the platypus and echidna is small compared to the same structure
      in both insectivores and primates, with the central and medial components of the
      temporal amygdala being particularly small.

PMID- 15993564
TI  - Positive and negative symptoms in affected sib pairs with schizophrenia:
      implications for genetic studies in an African Xhosa sample.
AB  - Careful phenotyping and the identification of subtypes of schizophrenia can
      contribute significantly to the success of genetic studies in schizophrenia. The
      phenomenology of schizophrenia in affected sib pairs has been well-described in
      Caucasian populations, however a paucity of data exists for African populations.
      This study therefore investigated symptom dimensions in a sizeable group of
      affected Xhosa sib pairs as a means of evaluating the role of shared familial
      factors in the psychosis of schizophrenia. Five hundred and thirteen participants
      were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which
      included the Schedules for the Assessment of Negative and Positive symptoms
      (SANS/SAPS). One hundred and four sib pairs were then extracted (N = 208) for
      analysis of concordance for lifetime psychotic symptoms and an exploratory factor
      analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a
      significant concordance for olfactory hallucinations, persecutory delusions,
      jealousy, somatic, reference and control delusions as well as thought insertion
      and withdrawal. The factor analysis of the global scores of the SAPS and SANS
      revealed a five factor best-fit model and accounted for 92.5% of variance. The
      factors included a negative symptom factor, a positive symptom factor, a positive
      thought disorder and a bizarre behaviour component. The core symptomatology of
      schizophrenia in this sib pair sample was similar to that reported in Caucasian
      populations with the exception of higher rates of auditory hallucinations and
      delusions of persecution. In summary therefore; although the factor analysis only
      supported the concept of the universality of psychotic symptoms in schizophrenia,
      the concordance analysis of these symptoms did reveal hallucinations as well as
      delusions of control as possible candidates relevant for future research into
      genotype-phenotype relationships.

PMID- 15993565
TI  - Examination of the trace amine-associated receptor 2 (TAAR2).

PMID- 15993566
TI  - The underlying structure of diagnostic systems of schizophrenia: a comprehensive
      polydiagnostic approach.
AB  - The objective was to ascertain the underlying factor structure of alternative
      definitions of schizophrenia, and to examine the distribution of schizophrenia
      related variables against the resulting factor solution. Twenty-three diagnostic
      schemes of schizophrenia were applied to 660 patients presenting with psychotic
      symptoms regardless of the specific diagnosis of psychotic disorder. Factor
      analysis of the 23 diagnostic schemes yielded three interpretable factors
      explaining 58% of the variance, the first factor (general schizophrenia factor)
      accounting for most of the variance (36%). On the basis of the general
      schizophrenia factor score, the sample was divided in quintile groups
      representing 5 levels of schizophrenia definition (absent, doubtful, very broad,
      broad and narrow) and the distribution of a number of schizophrenia-related
      variables was examined across the groups. This grouping procedure was used for
      examining the comparative validity of alternative levels of categorically defined
      schizophrenia and an ordinal (i.e. dimensional) definition. Overall,
      schizophrenia-related variables displayed a dose-response relationship with level
      of schizophrenia definition. Logistic regression analyses revealed that the
      dimensional definition explained more variance in the schizophrenia-related
      variables than the alternative levels for defining schizophrenia categorically.
      These results are consistent with a unitary and dimensional construct of
      schizophrenia with no clear "points of rarity" at its boundaries, thus supporting
      the continuum hypothesis of the psychotic illness.

PMID- 15993567
TI  - Subjective quality of life in subjects at risk for a first episode of psychosis:
      a comparison with first episode schizophrenia patients and healthy controls.
AB  - The concept of quality of life (QoL) is of growing relevance in schizophrenia
      research. However, there is to date no information on subjective QoL in subjects
      at risk for a first episode of psychosis in comparison to first episode
      schizophrenia patients (FE) or healthy controls (HC). Therefore 45 subjects in a
      putatively early initial prodromal state (EIPS), 40 FE and 45 HC were assessed on
      demographics, symptoms and subjective QoL as measured by the Modular System for
      Quality of Life. Results indicated that in most areas HC experienced the highest
      QoL scores followed in hierarchical order by EIPS and FE. EIPS and FE experienced
      significantly lower QoL than HC in 5 and 6 of 7 QoL domains. EIPS experienced the
      lowest ratings in affective QoL. Thus the data demonstrates that subjective QoL
      in subjects at risk for a first episode of psychosis is substantially reduced
      when compared with HC and suggests that subjective QoL is already compromised
      prior to the onset of first positive schizophrenia symptoms. These findings
      support the notion that subjects at risk for a first episode of psychosis
      constitute a clinical population for which further service and intervention
      research is indicated.

PMID- 15993568
TI  - N400 anomalies in schizophrenia are correlated with the severity of formal
      thought disorder.
AB  - We explored the link between N400 anomalies and clinical profile in schizophrenia
      patients. N400 was recorded in 50 schizophrenia patients and 40 healthy controls
      during a lexical decision task with semantic priming. Comparison between controls
      and schizophrenia patients showed the classical anomalies reported for N400 in
      schizophrenia patients: greater amplitude for related words and lack of N400
      effect. Analyses of the correlations between N400 effect and various symptoms of
      schizophrenia (formal thought disorder, positive symptoms, negative symptoms,
      overall symptoms, mean neuroleptic dose) or socioeducational data (age,
      vocabulary level, number of years of study) revealed that only the correlation
      with formal thought disorder was significant: the higher the scores for formal
      thought disorder, the lower the N400 effect observed.

PMID- 15993569
TI  - Matrikines and matricryptins: Implications for cutaneous cancers and skin repair.
AB  - Dermatologists are faced daily with the need to optimize skin repair and excise
      cutaneous cancers. The extracellular matrix plays a pivotal role in cellular
      migration, proliferation, and gene regulation during wound healing and
      progression of melanoma, basal cell carcinoma, and squamous cell carcinoma.
      Within the last few years, a new class of ligand, the matrikine or matricryptin,
      has been characterized as subdomains of various ECM proteins capable of signaling
      to the cell through receptors, such as growth factor receptors. Two classes
      exist: the "natural" matrikines, which signal directly from the extracellular
      milieu and "cryptic" matrikines (matricryptins) that require proteolytic
      processing to reveal the ligand or to release the ligand from its ECM protein.
      Unlike traditional soluble growth factors, most matrikines possess low binding
      affinity to their receptors and are often presented in multiple valency that
      likely increase avidity to receptors. The presentation of these ligands within
      the ECM can result in unique outcomes. The EGF-like repeats of tenascin-C and
      laminin-5 signal to EGFR preferentially to upregulate migration during skin
      repair and tumor progression. Other matrikines in collagen, elastin, decorin, and
      laminin-1 can promote chemotaxis, mitogenesis, and metastasis in cancers, such as
      melanoma. Finally, the unique properties of matrikines have been utilized in
      cancer therapeutics and tissue engineering. Within the next few years, the nature
      and function of this emerging class of matrikine ligands will have an impact on
      dermatology, as these proteins are altered in wound repair and skin diseases.

PMID- 15993570
TI  - Effects of UVB on fascin expression in dendritic cells and Langerhans cells.
AB  - BACKGROUND: Fascin is an actin-binding protein that regulates the rearrangement
      of cytoskeletal elements and their interactions with the cell membrane. Previous
      studies have indicated that fascin expression is enhanced in DC upon maturation
      and plays a critical role in T cell activation. Ultraviolet irradiation exerts
      immunosuppressive effects. OBJECTIVE: We examined the effects of UVB irradiation
      on the interaction of DC/LC with T cells through fascin. METHOD: Murine bone
      marrow-derived DC (BM-DC) were induced by recombinant murine GM-CSF and LPS, and
      UVB irradiation was applied prior to supplementation with LPS. I-A(+) cells
      (Langerhans cells (LC)) in the epidermal cell suspensions were exposed to UVB
      irradiation at the beginning of the 24-h culture. BM-DC and LC were analysed by
      immunohistochemical staining and flow cytometric analyses. To evaluate the
      effects of UVB irradiation on DC-T cell binding, we examined the clustering of BM
      DC with allogeneic CD4(+) T cells under a confocal microscope. RESULTS: Fascin
      expression in BM-DC and LC was decreased by UVB irradiation. Furthermore, UVB
      irradiation reduced the ability of BM-DC to cluster with allogeneic CD4(+) T
      cells. Polarization of fascin and filamentous actin (F-actin) at the point of
      contact of BM-DC with T cells was also disturbed by UVB irradiation. CONCLUSION:
      These results suggest that the suppression of fascin expression by UVB
      irradiation down-regulates the rearrangement of the cytoskeleton and, thereby,
      antigen presentation in DC/LC.

PMID- 15993571
TI  - Identification of different regions among strains of Yersinia pestis by
      suppression subtractive hybridization.
AB  - Yersinia pestis, the causative agent of bubonic and pneumonic plague, has been
      classified into four biovars: Antiqua, Mediaevalis, Orientalis and Microtus.
      Although the entire genome sequences of three Y. pestis strains, CO92, KIM and
      91001, of biovar Orientalis, Mediaevalis and Microtus, respectively, have been
      decoded, the genome sequence of the biovar Antiqua strain is unknown. In an
      initial effort to find Antiqua-specific sequences, suppression subtractive
      hybridization (SSH) was performed and four different regions (DFRs) were
      identified. Among the four DFRs, only DFR4 was specific to the tester (strain
      49006, biovar Antiqua). PCR demonstrated that DFR4 was present only in 57 of 60
      Antiqua strains from the Marmota baibacina-Spermophilus undulates plague focus in
      the Tianshan Mountains (focus B) and in three strains of Y. pseudotuberculosis
      (serotypes I and II), showing that not all Antiqua strains had DFR4. Five DFR
      profiles were identified based on the presence or absence of these four DFRs in
      636 strains of Y. pestis from 10 plague foci in China.

PMID- 15993572
TI  - Risk of suicide after attempted suicide in the population of Slovenia from 1970
      to 1996.
AB  - OBJECTIVE: All suicide attempts cannot predict suicide, therefore we examined
      those characteristics of suicide attempt which could most accurately predict
      completed suicide. SUBJECT AND METHODS: Subjects were all individuals registered
      as committed suicides (N=16,522) or attempted suicides (N=15,057) in the register
      of suicides of the Republic of Slovenia between 1970 and 1996. Log linear
      analysis of a frequency table was used to uncover relationship between
      categorical variables. RESULTS: The model we found fit between variables: mode,
      number of repetitions and type, then between number of repetitions, type and
      gender, and between mode, type and gender. DISCUSSION: The risk of suicide in
      those who previously attempted suicide is approximately 773 times higher than the
      risk of suicide without a previous suicide attempt. Those who attempt suicide by
      hanging (hanging being in Slovenia the most frequent mode of completed suicide)
      are at even greater risk to commit suicide. CONCLUSION: Our data suggests that
      clinicians should heighten their awareness that any suicide attempt can in some
      20% predict suicide. Someone who has attempted suicide by hanging is at the
      highest risk of suicide.

PMID- 15993573
TI  - Semantic divergence and creative story generation: an fMRI investigation.
AB  - The aim of this fMRI investigation was to identify those areas of the brain
      associated with approaching a story generation task creatively and to investigate
      the effects upon these correlates of incorporating a set of words that were
      unrelated to each other-a strategy considered to encourage semantic divergence.
      Preliminary experiments were undertaken to investigate the possible confounding
      effects of the scanner environment upon creativity and to reveal the effects of
      creative effort and word relatedness upon the creativity of those who would be
      participating in the fMRI scan. In the final part of the investigation, a
      factorial fMRI design was used to elucidate brain regions involved in increased
      creative effort and also the effect upon activity in these regions when
      participants incorporated words that bore little semantic relationship with each
      other. Results support the notion that areas of the right prefrontal cortex are
      critical to the types of divergent semantic processing involved with creativity
      in this context.

PMID- 15993574
TI  - Hemoptysis and coughing up of staples as a late complication of volume reduction
      surgery for emphysema.
AB  - Three patients with very similar clinical symptoms, i.e. hemoptysis and coughing
      up of staples some time after volume-reducing surgery, are described. There was
      no deterioration in lung function, nor in the patient's well-being, which could
      be ascribed to the coughing up of the staples. Thus, staples can some time after
      volume reducing surgery erode out into the bronchi and be coughed up, often with
      some small amounts of blood. This has no clinical significance other than the
      disturbing symptoms. Possibly, the calf pericardium used as strenghtener of the
      suture lines will with time cause an immunological reaction, causing destruction
      of the foreign material and thereby dislodging the staples.

PMID- 15993575
TI  - Large pleiomorphic traffic intermediates in the secretory pathway.
AB  - There are two main classes of traffic intermediates that operate in intracellular
      trafficking pathways: small round vesicles, and large pleiomorphic carriers
      (LPCs). While both are essential, the LPCs appear to be responsible for moving
      the bulk of the secretory traffic between distant compartments. LPCs are much
      larger and more variable in shape than vesicles, and they have evident
      interconnected tubular and saccular/cisternal components. They appear to form by
      en bloc extrusion and cleavage of large membrane areas of the donor organelle.
      Although many proteins and lipids that are involved in LPC formation have been
      identified, the intrinsic complexity of these carriers and current technical
      limitations mean that a coherent picture of the process of of LPC formation is
      only just beginning to emerge.

PMID- 15993576
TI  - New proteins in a materials world.
AB  - With the development of protein engineering, protein expression, and
      nano(bio)technologies, the ability to use 20 or more amino acids to design and
      produce genetically engineered protein materials is now possible. Proteins
      derived from natural sources offer one route for the production of new materials
      and many have been modified or formulated for improved performance. The
      development of synthetic polymer systems provides a second route to new
      materials: the concept of using a library of monomers and having the methods to
      precisely order them to design and produce a new polymer is a long-sought
      objective of polymer scientists. Recent advances have been made in the
      development of synthetic proteins for novel applications. Insight into the
      structures of some of nature's most intriguing materials, such as diatom
      frustules, has revealed a major role for proteins in facilitating and templating
      inorganic composites resulting in the development of bio-inspired materials.

PMID- 15993577
TI  - Protein-protein interactions in human disease.
AB  - Many human diseases are the result of abnormal protein-protein interactions
      involving endogenous proteins, proteins from pathogens or both. The inhibition of
      these aberrant associations is of obvious clinical significance. Because of the
      diverse nature of protein-protein interactions, however, the successful design of
      therapeutics requires detailed knowledge of each system at a molecular and atomic
      level. Several recent studies have identified and/or characterised specific
      interactions from various disease systems, including cervical cancer, bacterial
      infection, leukaemia and neurodegenerative disease. A range of approaches are
      being developed to generate inhibitors of protein-protein interactions that may
      form useful therapeutics for human disease.

PMID- 15993578
TI  - Human renal mesangial cells produce aldosterone in response to low-density
      lipoprotein (LDL).
AB  - Systemic aldosterone plays an important role in the development of the
      microvascular disease and glomerular damage of the kidney in patients with
      diabetes mellitus and hyperlipidemia. Here, we investigated the possibility of
      local production of aldosterone in the kidney, using human primary glomerular
      mesangial cells. These cells produced both pregnenolone and aldosterone measured
      by specific radioimmunoassay and/or gas chromatography/mass spectrometry (GC/MS)
      methods. The production of both steroids was significantly stimulated by
      treatment with LDL, while angiotensin II had a synergistic effect.
      Adrenocorticotropic hormone (ACTH) and (Bu)2cAMP, on the other hand, failed to
      stimulate aldosterone production by these cells, suggesting that the local
      production of this steroid by mesangial cells is regulated differently from that
      of adrenal zona glomerulosa cells. Mesangial cells expressed the mRNA of the LDL
      receptor and steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD), 21-hydroxylase and CYP11B2. Mesangial cells also
      expressed mRNA of the mineralocorticoid receptor (MR), and LDL stimulated its
      abundance by three-fold, while spironolactone, a completive antagonist of
      aldosterone, completely abolished this LDL effect. Since MR is a known
      mineralocorticoid-responsive gene as well as an intracellular receptor molecule
      for this steroid, these results suggest that locally produced aldosterone is
      biologically active, stimulating the transcription rates of the mineralocorticoid
      responsive genes by activating the MR in mesangial cells. These pieces of
      evidence indicate that human mesangial cells are an aldosterone-producing tissue
      in which LDL plays a major regulatory role. Therefore, human renal mesangial
      endocrine system may contribute to local aldosterone concentrations and effects
      in the renal glomerulus independently of the systemic renin--angiotensin-
      aldosterone system and may participate in the development and progression of
      glomerular damage in several pathologic conditions.

PMID- 15993579
TI  - Molecular changes in prostatic cancer.
AB  - Prostate cancer is one of the most commonly diagnosed and potentially devastating
      cancers in men, throughout the world. However, the clinical manifestation of this
      disease varies greatly, from indolent tumours, requiring little or no treatment,
      to those aggressive cancers which require radical therapies. Prostate cancer,
      like all other cancers, develops and progresses as a consequence of an
      accumulation of genetic changes. While several putative genes have been isolated
      for the development of breast, ovarian and colon cancer, the aetiology and
      pathogenesis of prostate cancer remains poorly understood. In this review, we
      discuss important genetic markers in early, metastatic and hormone refractory
      prostate cancer which may, in the future, be used as markers for diagnosis and
      prognosis, as well as targets for therapeutic intervention.

PMID- 15993580
TI  - Isolation of free-living dinitrogen-fixing bacteria and their activity in compost
      containing de-inking paper sludge.
AB  - Knowledge of the microbiology of dinitrogen (N2)-fixing bacteria in compost rich
      in de-inking paper sludge (DPS) is limited. Dinitrogen (N2)-fixing bacteria from
      DPS composts were isolated and studied for their N2-fixing activity in vitro and
      in vivo. Two Gram-negative N2-fixing isolates were identified as Pseudomonas. At
      20 degrees C, both isolates revealed that N2-fixing activity was higher than that
      of three arctic Pseudomonas strains. Their N2-fixing activity was found to occur
      between 18 and 25 degrees C, a pattern that was similar to the reference isolate
      Azotobacter ATCC 7486. Composts successfully showed N2-fixing activity after
      carbohydrate amendments both with and without inoculation of a N2-fixing isolate.
      These results suggest that DPS composts support N2-fixing bacteria and that N2
      fixing activity is dependent on a usable carbohydrate source.

PMID- 15993581
TI  - Low cost bio-sorbent 'wheat bran' for the removal of cadmium from wastewater:
      kinetic and equilibrium studies.
AB  - Novel bio-sorbent wheat bran has been successfully utilized for the removal of
      cadmium(II) from wastewater. The maximum removal of cadmium(II) was found to be
      87.15% at pH 8.6, initial Cd(II) concentration of 12.5 mg l-1 and temperature of
      20 degrees C. The effect of different parameters such as contact time, adsorbate
      concentration, pH of the medium and temperature were investigated. Dynamics of
      the sorption process were studied and the values of rate constant of adsorption,
      rate constant of intraparticle diffusion and mass transfer coefficient were
      calculated. Different thermodynamic parameters viz., changes in standard free
      energy, enthalpy and entropy have also been evaluated and it has been found that
      the reaction was spontaneous and exothermic in nature. The applicability of
      Langmuir isotherm showed of monolayer coverage of the adsorbate on the surface of
      adsorbent. A generalized empirical model was proposed for the kinetics at
      different initial concentrations.

PMID- 15993582
TI  - Hydrophobicity in the design of P2/P2' tetrahydropyrimidinone HIV protease
      inhibitors.
AB  - As part of an ongoing effort in understanding the role of hydrophobicity in the
      design of nonpeptidic HIV protease inhibitors, the QSAR study on P2/P2'
      tetrahydropyrimidinone is presented in this report. Our results suggest that the
      balance of hydrophobicity and a volume- dependent polarizability term plays a key
      role in the inhibition of the viral protease by these inhibitors. The size of the
      substituent of ligands at particular positions that induce steric fit is crucial.
      The role of hydrophobicity in the design of tetrahydropyrimidinone is discussed.
      It has been found that a sufficient spread in the data is required to observe the
      optimum value of ClogP for these inhibitors.

PMID- 15993583
TI  - Synthesis of novel curcumin mimics with asymmetrical units and their anti
      angiogenic activity.
AB  - Novel curcumin mimics with asymmetrical units phenyl group with alkyl amide,
      chloro-substituted benzamide, or heteroaromatic amide moieties were synthesized
      and their anti-angiogenic activity was evaluated with the proliferation and tube
      formation inhibitory activity on the human umbilical vein endothelial cells.
      Compounds 5, 14, 17, and 18 showed potent growth inhibitory activity and tube
      formation inhibitory activity.

PMID- 15993584
TI  - Induction of apoptosis by a novel indirubin-5-nitro-3'-monoxime, a CDK inhibitor,
      in human lung cancer cells.
AB  - A novel indirubin analog, indirubin-5-nitro-3'-monoxime, inhibited cell
      proliferation against various human cancer cells. Additional studies indicate
      that the mechanism of action of this analog against human lung cancer cells might
      be to arrest cell cycle progression at the G2/M phase and induce apoptosis via
      p53- and mitochondria-dependent pathways. These data suggest that indirubin-5
      nitro-3'-monoxime might be a novel candidate for development of anticancer
      agents.

PMID- 15993585
TI  - Synthesis of benzoyl phenyl benzoates as effective inhibitors for phospholipase
      A2 and hyaluronidase enzymes.
AB  - Benzoylation of (hydroxy phenyl) phenyl methanone 2a-g to benzoyl phenyl
      benzoates 4a-g, a benzophenone analogue, was achieved in good yield. All the
      newly synthesized compounds were evaluated for their phospholipase A2 [E.C.
      3.1.1.4] and hyaluronidase [E.C. 3.2.1.35] enzyme inhibitory activity in snake
      venom as source and their structure-activity relationship with respect to
      different groups is reported for the first time. The in vitro PLA2 enzyme
      inhibitory activity and in vivo anti-inflammatory activity studies of benzoyl
      phenyl benzoates are illustrated.

PMID- 15993587
TI  - Ketoheterocycle-based inhibitors of cathepsin K: a novel entry into the synthesis
      of peptidic ketoheterocycles.
AB  - Ketoheterocyclic inhibitors of cathepsin K have been disclosed. SAR of potency
      enhancing P2-P3 groups coupled with ketoheterocyclic warheads to provide
      cathepsin K inhibitors have been described. In addition, a novel route to access
      alpha-ketothiazoles using a key thioamide functionality has been disclosed. The
      mild method employed allows for the presence of diverse functional groups, such
      as amide and carbamate functionalities, commonly found in protease inhibitors
      that have peptidomimetic scaffolds. This new method should provide a quick entry
      into functionally diverse protease inhibitors.

PMID- 15993586
TI  - Identification of novel angiogenesis inhibitors.
AB  - Vascular endothelial growth factor (VEGF) is a key stimulant of angiogenesis,
      which is the process of generating new capillary blood vessels. Inhibition of the
      vascular endothelial growth factor receptor (VEGFR) kinase is known to result in
      blockage of angiogenesis. A pharmacophore was developed based on the binding of
      ATP to the hinge region of the kinase domain of VEGFR and a database search of
      18,000 compounds was conducted. Selected hits were assessed for their ability to
      limit the induction of web-like network of capillary tubes by the human umbilical
      vascular endothelial cells. Two compounds (1 and 4) showed good inhibitory
      ability to prevent sprouting and closed polygon formation of the tubular
      networks, promising them to be lead compounds. Compound 4 showed 60% inhibition
      at 0.05 microM.

PMID- 15993588
TI  - In vitro binding of leukotriene B4 (LTB4) to human serum albumin: evidence from
      spectroscopic, molecular modeling, and competitive displacement studies.
AB  - Circular dichroism (CD) and UV absorption spectroscopy were utilized for the
      first time to investigate the interaction between leukotriene B4 (LTB4) and human
      serum albumin (HSA) in vitro. The weak intrinsic CD signal of LTB4 was enhanced
      fivefold in the presence of HSA. The red-shifted, hypochromic, and reduced
      vibrational fine structure of the ligand/protein UV absorption spectrum indicated
      complexation of the two molecules in solution. Results obtained from CD titration
      experiments were subjected to non-linear regression analysis to estimate the
      binding parameters (Ka = 6.7 x 10(4) M(-1), n = 1). Palmitic acid strongly
      decreased the induced CD signal of the LTB4/HSA complex, suggesting the role of a
      high-affinity fatty acid HSA binding site in the leukotriene complexation.
      Molecular modeling calculations based on the crystal structure of HSA predicted
      that the long-chain fatty acid site that overlaps with drug binding site II in
      subdomain IIIA was the most likely binding location for LTB4. Using the drug site
      II-specific marker ligand rac-ibuprofen, this prediction was confirmed with
      induced-CD displacement measurements. To the authors' knowledge, the current
      study represents the first demonstration of binding of LTB4 to HSA in vitro and
      has implications for the biological transport of this important pro-inflammatory
      mediator in vivo.

PMID- 15993589
TI  - Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A
      analogues.
AB  - Salvinorin A is the most potent naturally occurring opioid agonist yet discovered
      with high selectivity and affinity for kappa-opioid receptor. To explore its
      structure and activity relationships, a series of salvinorin A derivatives
      modified at the C2 position were prepared and studied. These salvinorin A
      derivatives were screened for binding and functional activities at the human
      kappa-opioid receptor. Compound 4, containing a methoxymethyl group at the 2
      position, was a full kappa-agonist with an EC50 value at 0.6 nM, which is about 7
      times more potent than salvinorin A.

PMID- 15993590
TI  - Contribution of site-specific PEGylation to the dipeptidyl peptidase IV stability
      of glucose-dependent insulinotropic polypeptide.
AB  - The effects of PEGylation of glucose-dependent insulinotropic polypeptide (GIP)
      on potency and dipeptidyl peptidase IV (DPPIV) stability are reported. N-terminal
      modification of GIP(1-30) with 40 kDa polyethylene glycol (PEG) abrogates
      functional activity. In contrast, C-terminal PEGylation of GIP(1-30) maintains
      full agonism and reasonable potency at the GIP receptor and confers a high level
      of DPPIV resistance. Moreover, the dual modification of N-terminal palmitoylation
      and C-terminal PEGylation results in a full agonist of comparable potency to
      native GIP that is stable to DPPIV cleavage. The results provide the basis for
      the development of long acting, PEGylated GIP, GIP variants, or GIP-based hybrid
      peptide therapeutics.

PMID- 15993591
TI  - SAR and biological evaluation of novel trans-3,4-dimethyl-4-arylpiperidine
      derivatives as opioid antagonists.
AB  - The phenolic hydroxy group of opiate-derived ligands is of known importance for
      biological activity. We have developed a SAR study around LY255582 by comparing
      the effect of the hydroxy group in the 2- and 4-position of the phenyl ring.
      Also, we have proved that the 3-position of the phenyl ring is optimal for opioid
      activity. Furthermore, we have successfully replaced the hydroxy group in
      LY255582 by carbamate and carboxamide groups. The new analogs have high affinity
      for the opioid receptors comparable to the corresponding phenol. Carboxamide
      analog 12 has an improved metabolism profile and proved to be efficacious in in
      vivo studies.

PMID- 15993592
TI  - Developing microcolin A analogs as biological probes.
AB  - Three microcolin A and B analogs have been synthesized. Their biological activity
      profiles were evaluated against several cell lines, revealing the existence of a
      structural determinant whose role in mediating the antiproliferative effect of
      the microcolins has heretofore gone unrecognized. While previously described as
      potent immunosuppressive natural products, we found that these microcolin analogs
      possessed no selective cytotoxicity when comparing immune cell versus nonimmune
      cell proliferation. In addition, the amino-terminus of microcolin A has been
      modified to incorporate a biotinylated polyethylene glycol linker. The biological
      activity of this biotinylated microcolin A analog was determined. This affinity
      reagent was shown to retain limited biological activity and thus can serve as a
      useful probe for elucidating the mechanism of action of microcolin A.

PMID- 15993593
TI  - A 3D-QSAR model for CYP2D6 inhibition in the aryloxypropanolamine series.
AB  - A comparative molecular similarity index analysis (CoMSiA) has been performed for
      cytochrome P450 2D6 inhibition on a series of aryloxypropanolamines to determine
      the factors contributing to this activity. The model is in agreement with a
      CYP2D6 homology model constructed on the basis of the mammalian CYP2C5 crystal
      structure. The energy minimized conformations were generated using the systematic
      search methodology in Sybyl 6.7. The model not only elucidated the relationship
      between structure and biological activity but, more importantly, provided useful
      strategies to modulate CYP2D6 affinity in the aryloxypropanolamine series.

PMID- 15993594
TI  - In vitro antiproliferative activity against human colon cancer cell lines of
      representative 4-thiazolidinones. Part I.
AB  - The characterization of two cyclooxygenase isoforms (COX), the rate-limiting
      enzyme for the synthesis of prostaglandins (PGs) from arachidonic acid, has
      allowed the development of COX-2 selective inhibitors as non-steroidal anti
      inflammatory drugs (NSAIDs) with significant gastric tolerability. However, PGs
      are also important in cancer pathogenesis. Thus, there is an increasing interest
      in studying COX-2 inhibitors as potential drugs aimed at the prevention and
      treatment of cancer, especially colorectal cancer. The purpose of this study was
      to determine the inhibitory effects of some representative 4-thiazolidinones,
      already widely investigated as potential NSAIDs, on the growth of five human
      colon carcinoma cell lines with a different COX-2 expression, and to correlate
      them with COX-2 inhibitory properties. Our results preliminarily revealed that 2
      phenylimino derivative 3 and 2,4-thiazolidindione 4 were the most active
      compounds. In particular, 3 mainly inhibited the HT29 cell line characterized by
      a high COX-2 expression, whereas 4 showed antiproliferative properties on all
      tested cell lines, suggesting molecular targets other than COX-2 inhibition.

PMID- 15993595
TI  - Structure-based design, synthesis, and in vitro assay of novel nucleoside analog
      inhibitors against HIV-1 reverse transcriptase.
AB  - Crystal structure of HIV-RT in complex with a DNA template:primer and a dTTP
      leads us to design and synthesize a new class of nucleoside analog inhibitors
      containing a branched 3'-group against HIV-RT. An in vitro primer extension assay
      indicates that three out of five compounds are effective HIV-RT inhibitors.

PMID- 15993596
TI  - Bradykinin B1 antagonists: SAR studies in the 2,3-diaminopyridine series.
AB  - SAR study of the biphenyl region of 2,3-diaminopyridine bradykinin B1 antagonists
      was investigated with non-aromatic carbo- and heterocyclic rings. A piperidine
      ring was found to be a good replacement for the proximal phenyl ring while
      replacement of the distal phenyl was optimal with a cyclohexyl group leading to a
      dramatic improvement in affinity for the B1 receptor.

PMID- 15993597
TI  - Synthesis and evaluation of photolabile insulin prodrugs.
AB  - We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P.
      These prodrugs were synthesized by protecting GlyA1 (N(alphaA1)), and one or both
      of the PheB1 (N(alphaB1)) and LysB29 (N(epsilonB29)) amino groups in insulin
      using 5'-(alpha-methyl-nitro-piperonyl)oxy-carbonyl as the protecting group.
      These insulin prodrugs were efficiently activated by exposure to longwave UV
      light to produce insulin quantitatively. Using 2-deoxyglucose uptake assays, both
      di- and tri-protected compounds were less active than native insulin in the
      protected state, and showed comparable activity to native insulin upon
      photoactivation.

PMID- 15993598
TI  - 4-Fluorosulfonylpiperidines: selective 5-HT2A ligands for the treatment of
      insomnia.
AB  - Incorporation of fluorine at the 4-position of an existing series of sulfonyl
      piperidine 5-HT2A antagonists gave compounds with increased selectivity over the
      IKr potassium channel. This work led to the identification of 3b, a compound that
      gave no increase in QTc in the anesthetized dog up to plasma levels as high as
      148 microM. Furthermore, 3b has been shown to increase slow-wave sleep bout
      duration and to decrease the number of awakenings in rats, indicating the
      potential utility of 5-HT2A antagonists in the treatment of insomnia.

PMID- 15993599
TI  - A carbon-carbon-coupled dimeric bergenin derivative biotransformed by Pleurotus
      ostreatus.
AB  - A novel C-C-coupled dimer derivative of bergenin was produced by the
      biotransformation of cultured mycelia of white rot fungus Pleurotus ostreatus.
      Its structure was elucidated by detailed spectroscopic analysis.

PMID- 15993600
TI  - Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as
      acetylcholinesterase inhibitors.
AB  - A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized,
      and tested as acetylcholinesterase inhibitors. The most potent compound exhibited
      high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study
      indicated that it was nicely accommodated by AChE.

PMID- 15993601
TI  - Management of big osteochondral defects of the knee using osteochondral
      allografts with the MEGA-OATS technique.
AB  - Treatment of osteochondral defects in weight-bearing areas of the knee,
      especially when they are sizeable and involve considerable subchondral bone loss,
      is a challenging problem. We report our experience on the use of osteochondral
      allografts with the MEGA-OATS technique in the management of large osteochondral
      defects of the knee in young patients. Five patients (3 male and 2 female) were
      included in this study; their age ranged from 22 to 41 years and the mean size of
      the defect covered was 30 x 30 mm. They were followed for a minimum of 2.5 years
      (mean: 32.8 months, range 30-36). An age- and size-matched fresh frozen, non
      irradiated distal femoral allograft was used to obtain the donor plug, which was
      then inserted in the recipient area in a press-fit fashion. Patients' Lysholm
      knee score increased from 37.8 pre-operatively to 73.8 post-operatively. Tegner
      activity score increased in all five patients; it improved from a mean of 2 pre
      operatively (range 1-3) to 4 post-operatively (range 2-7). Four out of five
      patients returned to work and three went back to sporting activities. With this
      technique one can cover sizeable osteochondral defects, and compensate for
      significant subchondral bone loss, while accurate reconstruction of the curvature
      of the femoral condyle is allowed. We believe that it is a viable salvage option
      in young patients with big osteochondral defects of the knee. It offers very
      satisfactory functional results and does not compromise patients' future options.

PMID- 15993602
TI  - Tibiofemoral instability in primary total knee replacement: a review, Part 1:
      Basic principles and classification.
AB  - Tibiofemoral instability following total knee replacement has received little
      attention. However it is a cause of early and late failure and usually requires
      revision surgery. Several factors may be implicated including improper soft
      tissue balancing, flexion-extension gap mismatch and acute ligamentous injuries.
      Meticulous surgical technique and proper prosthetic selection at the primary
      procedure avoids this complication.

PMID- 15993603
TI  - The effect of screw taper on interference fit during load to failure at the soft
      tissue/bone interface.
AB  - The effect of screw geometry on the pullout strength of an anterior cruciate
      ligament reconstruction is well documented. The effect of a truly tapered screw
      has not been previously investigated. Thirty bovine knees in right and left knee
      pairs were collected. Superficial digital flexors from the hind legs of sheep
      were harvested to form a quadruple tendon graft. For each knee pair, one tendon
      graft was fixed using a tapered screw (n=15) and the other with a non-tapered
      screw (n=15). Interference screws were manufactured from stainless steel, and
      apart from the tapered or non-tapered profile were identical. The screws were
      inserted into a tibial tunnel already containing the tendon graft. The
      interference fit was tested by extensile load to failure tests. The insertion
      torque of the screws and first sign of load to failure (by pullout) of the
      interference fit were recorded. Results were analysed using paired t-tests. The
      results indicated that tapered screws have significantly higher resistance to
      interference failure (p=0.007) and insertion torque (p<0.001) than non-tapered
      screws. The improved biomechanical performance of tapered screws demonstrated in
      this study may translate into superior clinical results, particularly at the
      tibial attachment of hamstring anterior cruciate ligament reconstruction, and
      also of hamstring fixation to the medial femoral condyle for patella instability.

PMID- 15993604
TI  - The Oxford Knee Score; problems and pitfalls.
AB  - The Oxford Knee Score is a self-completed patient based outcome score. We audited
      the outcome of total knee arthroplasty at our unit using the Oxford Knee Score.
      The hypothesis of this study is that the OKS can be easily and accurately
      completed by unassisted patients. Of 856 patients who had undergone total knee
      arthroplasty and were given questionnaires, 769 (90%) responded. 624 (81%) of the
      respondents managed to complete the questionnaire. A number of the 12 items
      composing the questionnaire posed problems for the patients and a number of items
      were left blank. Item 4 (concerning walking time) was omitted in 82 (13%) of the
      624 completed questionnaires. Calculation of Cronbach's alpha for internal
      consistency suggests that there are redundancies within the Score. Limitations in
      some of the items of the scale suggest the need for reconsideration and
      reformulation of questions and response categories. This study suggests that
      where detailed assessment of outcome is required, such as for outcome studies or
      controlled trials, the Oxford Knee Score, in its present form, is not ideal for
      use as a postal questionnaire.

PMID- 15993605
TI  - Density-functional theory and ab initio Hartree-Fork studies on the structural
      parameters and chemical activity of the free radicals generated by benzoquinone
      and hydroquinone.
AB  - Density-functional theory (DFT) calculations were performed for calculation of
      the theoretical spectra and the chemical activities of free radicals generated by
      benzoquinone and hydroquinone as well as the transition states, and the
      calculated spectra were used for the assignment of the frequencies observed in
      the experimental IR spectra. The calculated geometrical parameters, the predicted
      IR spectra, and the chemical activities of free radicals and transition states
      were also compared with those of benzoquinone and hydroquinone. The reactive
      mechanisms of free radicals generated by benzoquinone and hydroquinone are also
      discussed using ab initio Hartree-Fork (HF) methods.

PMID- 15993606
TI  - Design, synthesis, and AMPA receptor antagonistic activity of a novel 6-nitro-3
      oxoquinoxaline-2-carboxylic acid with a substituted phenyl group at the 7
      position.
AB  - We describe the design, synthesis, and biological properties of a novel series of
      7-substituted 6-nitro-3-oxoquinoxaline-2-carboxylic acids. After designing,
      studying the structure-activity relationships, and evaluating the properties of
      various compounds, we found that 7-heterocyclic-6-nitro-3-oxoquinoxaline-2
      carboxylic acids that contain a substituted phenyl group linked through urethane
      at the 7 position possess good alpha-amino-3-hydroxy-5-methylisoxazole propionate
      receptor (AMPA-R) antagonistic activity. Among the compounds tested, compound 29p
      (GRA-293), which has a 4-carboxy group on the terminal phenyl moiety, exhibited
      high potency and selectivity for the AMPA-R in vitro and good neuroprotective
      efficacy in vivo. It also showed good aqueous solubility.

PMID- 15993607
TI  - Four diterpenoid inhibitors of Cdc25B phosphatase from a marine anemone.
AB  - Three new diterpenoids and one known diterpenoid have been isolated from a sea
      anemone of the order Actiniara, and the structures of the new compounds,
      actiniarins A-C (1-3) were established on the basis of extensive 1D and 2D NMR
      spectroscopic data interpretation. Compound 1 has a six-membered ring hemiacetal
      ring, and the equilibrium of this ring is discussed. All the isolates were
      evaluated for their inhibition of Cdc25B and for cytotoxicity against the A2780
      ovarian cancer cell line.

PMID- 15993608
TI  - Libertellenones A-D: induction of cytotoxic diterpenoid biosynthesis by marine
      microbial competition.
AB  - The induction of biosynthesis of four new diterpenoids was observed following the
      addition of a marine alpha-proteobacterium to an established culture of the
      marine-derived fungus Libertella sp. The fungal strain and the marine bacterium,
      cultured alone, do not produce diterpenoid metabolites. The induced diterpenoids,
      libertellenones A-D, are cross-conjugated ketones of the pimarane class. The
      libertellenones show varying levels of cytotoxicity against the HCT-116 human
      adenocarcinoma cell line with libertellenone D being the most potent (IC50 = 0.76
      microM).

PMID- 15993609
TI  - A quantitative structure-activity relationship study on some series of
      anthranilic acid-based matrix metalloproteinase inhibitors.
AB  - A quantitative structure-activity relationship (QSAR) study has been made on four
      different series of anthranilic acid-based matrix metalloproteinase (MMP)
      inhibitors, in which two substituted aryl rings, one bearing the hydroxamic acid
      moiety that binds with the zinc atom of MMPs, are joined through a bridge group
      of sulfonamide. The QSAR results indicate that the sulfonamide group plays a very
      important role in the inhibition activity of the inhibitors and that the
      effectiveness of this sulfonamide group can be increased by the presence at the
      aryl rings or at the sulfonamide nitrogen itself of nitrogen-containing or some
      such substituents that can increase the electronic character of the sulfonamide
      group. The hydrophobic character of the molecules is not found to be of any
      advantage; rather in most of the cases it is shown to have detrimental effect,
      suggesting that MMPs provide little opportunity to the inhibitors to have a any
      hydrophobic interactions with them. On the other hand, polarizability of the
      molecules has been found to be conducive to activity in some cases. Thus the
      inhibition mechanism seems to predominantly involve the electronic interactions
      between the inhibitors and the enzymes.

PMID- 15993610
TI  - Synthesis and preliminary biological evaluation of O6-[4-(2
      [18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA
      repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy.
AB  - A novel fluorine-18-labeled O6-benzylguanine (O6-BG) derivative, O6-[4-(2
      [18F]fluoroethoxymethyl)benzyl]guanine (O6-[18F]FEMBG, [18F]1), has been
      synthesized for evaluation as a potential positron emission tomography (PET)
      probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) in
      cancer chemotherapy. The appropriate radiolabeling precursor N(2,9)-bis(p
      anisyldiphenylmethyl)-O6-[4-(hydroxymethyl)benzyl]guanine (6) and reference
      standard O6-[4-(2-fluoroethoxymethyl)benzyl]guanine (O6-FEMBG, 1) were
      synthesized from 1,4-benzenedimethanol and 2-amino-6-chloropurine in four or six
      steps, respectively, with moderate to excellent chemical yields. The target
      tracer O6-[18F]FEMBG was prepared in 20-35% radiochemical yields by reaction of
      MTr-protected precursor 6 with [18F]fluoroethyl bromide followed by quick
      deprotection reaction and purification with a simplified Silica Sep-Pak method.
      Total synthesis time was 60-70 min from the end of bombardment. Radiochemical
      purity of the formulated product was >95%, with a specific radioactivity of >1.0
      Ci/micromol at the end of synthesis. The activity of unlabeled O6-FEMBG was
      evaluated via an in vitro AGT oligonucleotide assay. Preliminary findings from
      biological assay indicate that the synthesized analogue has similarly strong
      inhibiting effect on AGT in comparison with O6-BG and O6-4-fluorobenzylguanine
      (O6-FBG). The results warrant further in vivo evaluation of O6-[18F]FEMBG as a
      new potential PET probe for AGT.

PMID- 15993612
TI  - Structure-activity studies of 3'-4'-dichloro-meperidine analogues at dopamine and
      serotonin transporters.
AB  - The structure-activity relationships of 3',4'-dichloro-meperidine were
      investigated at dopamine (DAT) and serotonin transporters (SERT). Large ester
      substituents and lipophilic groups at the 4-position favored molecular
      recognition at the SERT. The benzyl ester of 3',4'-dichloro-meperidine exhibited
      high potency and high selectivity for the SERT (DAT/SERT=760). Chemical
      modification of the ester group and N-substitution generally led to compounds
      with decreased DAT affinity. Only small esters and alkyl groups were tolerated at
      the 4-position of the meperidine ring system by the DAT. Overall, the meperidine
      analogues were generally more selective for the SERT than for the DAT.

PMID- 15993611
TI  - Antiviral cyclic D,L-alpha-peptides: targeting a general biochemical pathway in
      virus infections.
AB  - Diverse virus families have evolved to exploit the acidification of endosomal
      compartments to gain entry into cells. We describe a supramolecular approach for
      selectively targeting and inhibiting viral infections through this central
      biochemical pathway. Using adenovirus as a model non-enveloped virus, we have
      determined that an eight-residue cyclic D,L-alpha-peptide, selected from a
      directed combinatorial library, can specifically prevent the development of low
      pH in endocytic vesicles, arrest the escape of virions from the endosome, and
      abrogate adenovirus infection without an apparent adverse effect on cell
      viability. The likely generality of this approach against other pH-dependent
      viral infections is supported by the inhibition of type-A influenza virus escape
      from endosomes in the presence of the same peptide. Our studies suggest that self
      assembling cyclic D,L-alpha-peptides hold considerable potential as a new
      rational supramolecular approach toward the design and discovery of broad
      spectrum antiviral agents.

PMID- 15993613
TI  - Design, syntheses, and biological evaluations of squamostolide and its related
      analogs.
AB  - Squamostolide and its related analogs were designed and synthesized for
      biological evaluation. All these compounds were tested for growth inhibition
      activities against human tumor cell lines, in which one of the compounds showed
      the most potent cytotoxicity among these derivatives against a full panel of 60
      human cancer cell lines. The same compound also showed G2/M phase arrest and a
      weak apoptotic effect during flow cytometric analysis.

PMID- 15993614
TI  - Design, synthesis, and biological characterization of potential antiatherogenic
      nitric oxide releasing tocopherol analogs.
AB  - Synthesis and biological characterization of a series of alpha-tocopherol analogs
      with NO-releasing capacity are reported. The selected NO-donor moieties were
      nitrooxy and furoxan. All products were tested for their in vitro NO-releasing
      capacities, vasodilating properties, and antiplatelet activity. They were also
      capable of preventing LDL oxidation.

PMID- 15993615
TI  - The solution structure of a lasalocid A metal complex in lipophilic solvents.
AB  - Lasalocid A (LasNa), a common antibiotic in veterinary medicine, is a polyetheral
      ionophore, disrupting cation equilibria through the cell wall. By means of
      circular dichroism (in the UV and in the near-IR), paramagnetic NMR, and with the
      aid of the program PERSEUS, we determined the solution geometry of the 1:1 Las
      Yb3+ complex in CD3CN and CDCl3, following a protocol similar to the one
      successfully used for the anthracycline-metal adduct. The resulting structure is
      in full agreement with the expectation of the ligand wrapping around the cation
      in a horseshoe shape. The oxygen atoms participate in the coordination either
      through a direct, first sphere, or a longer range interaction.

PMID- 15993616
TI  - Synthesis and DNA-binding affinities of monomodified berberines.
AB  - Four new monomodified berberines have been synthesized in moderate to good yields
      starting from berberine and fully characterized by HRMS and 1H NMR. Spectrometric
      titration and ethidium bromide displacement experiments indicate that these
      berberine derivatives, especially the one having primary amino group, strongly
      bind with calf-thymus DNA, presumably via an intercalation mechanism.

PMID- 15993617
TI  - Use of nuclear techniques to determine the fill of found unexploded ordnance.
AB  - The PELAN is a man-portable device that uses pulsed neutrons to interrogate
      objects in order to determine their filler. The neutrons initiate several types
      of nuclear reactions within the object under scrutiny, which result in the
      formation of gamma rays. The energy of the resulting gamma rays provides
      information about the elements (carbon, hydrogen, oxygen, nitrogen) contained
      within the object; in addition the number of gamma rays detected provides
      information about how much of each element is present. An analysis of the
      elements present and their ratios to one another allows for identification of the
      filler material.

PMID- 15993618
TI  - Optimization of evaporation and counting times for measurements of short-lived
      gamma-ray emitters in water samples.
AB  - A methodology how to optimize the throughput of a laboratory when the sample
      preparation and sample measurement times are related is presented for the case
      when radioactive decay during the processing time cannot be neglected. It is
      assumed that the sensitivity of the measurements is prescribed and can be
      attained by processing a larger sample quantity or by extending the measuring
      time. The methodology is illustrated for measurements of 131I in samples of the
      dry residue obtained by evaporation of water. It is demonstrated that the
      quantities which determine the throughput of the laboratory are the maximum
      sample size which can be processed, the evaporation rate and the quality of the
      spectrometers.

PMID- 15993619
TI  - Plane rectangular tritium target response to excitation by uniform distributed
      normal accelerated deuteron beam.
AB  - This work is a contribution to analytical study of the spatial dependency of the
      d-T mean neutron energy in the vicinity of a homogeneous tritium-occluded
      rectangular plane target. An accelerated deuteron beam excites the tritium target
      with normal incidence to the target plane. The transverse density of accelerated
      deuteron beam is assumed to be constant close to the target. Due consideration
      being paid to d-T collision kinetics, depending upon mass and kinetic energy of
      particles involved in the nuclear collision, nuclear reaction energy, etc, in
      particular circumstances, the elementary neutron energy emission in non
      dispersive media can be considered to be omni-directional or very low
      anisotropical. Consequently, analytical expressions can be considerably
      simplified, taking into account the exothermic character of d-T fusion reaction.
      A number of expressions for energetic prediction of the fast neutron generated,
      in this case, by d-T reaction are proposed. Animated three-dimensional-graphics
      is suggested. Computationally tractable tools are of importance in the study of
      some situations such as induced reactions and activation analysis using 14MeV
      neutrons, investigations in health-physics, radiation dose characterization,
      nuclear medicine, damage effects, and simulation studies.

PMID- 15993620
TI  - Anthocyanin accumulation and changes in CHS and PR-5 gene expression in
      Arabidopsis thaliana after removal of the inflorescence stem (decapitation).
AB  - Anthocyanin accumulation occurs in rosette leaves of Arabidopsis thaliana within
      8 days after removal of the inflorescence stem. Expression of stress-induced
      genes CHS and PR-5 was strongly up-regulated by stem removal, and was highest on
      day 4 after decapitation. These levels were 10 and 5 times higher than in the
      control, respectively. No obvious difference was found in expression of LHCB,
      MEB5.2, or PYROA genes following stem removal. We demonstrate that removing the
      inflorescence stem triggers events in Arabidopsis, including pigment accumulation
      and changes in gene expression of a subset of stress-induced genes, in a tissue
      distant from the wound site.

PMID- 15993621
TI  - Three dimensional computed tomographic imaging in planning the surgical approach
      for redo cardiac surgery after coronary revascularization.
AB  - OBJECTIVE: Reoperative cardiac surgery after previous coronary artery bypass
      grafting represents a surgical challenge due to the potential for injury to
      patent coronary grafts, aorta or right ventricle. Standard preoperative imaging
      using a coronary angiogram and chest radiograph (CXR) often results in inaccurate
      assessment of mediastinal anatomy. We aimed to evaluate 3D volume rendered
      computed tomographic imaging as an adjunct to standard preoperative assessment of
      patients requiring cardiac surgery in whom coronary artery revascularization had
      been performed in the past. METHODS: Between January 2003 and January 2004, 33
      patients with previous coronary revascularization referred for reoperative
      cardiac surgery underwent preoperative 3D CT imaging in order to optimize the
      surgical approach. The mean age in this patient population was 72+/-8 years. The
      combined evaluation of CXR and conventional angiography offered incomplete
      insight into pertinent mediastinal topography in 85% of patients (28/33).
      RESULTS: The correlations for distances of the left internal mammary artery
      (LIMA) to left anterior descending artery (LAD) graft from the midline and
      posterior sternum obtained by CT angiography (CTA) and CXR were poor, R=0.56 and
      0.49, respectively. The correlation coefficients for distances between the right
      ventricle and the aorta to the sternum obtained by the same methods were
      similarly marginal, 0.58 and 0.48, respectively. The correlation coefficients for
      distances between the LIMA to LAD, circumflex and right coronary artery grafts
      from the midline obtained by CTA and conventional angiography were 0.54, -0.13
      and 0.43, respectively. In seven patients (21%) the surgical strategy was
      modified based on the location of patent grafts in the mediastinum. The hospital
      mortality was 17% (5/29). Intraoperative injuries to vital structures were
      encountered in two patients (7%). No injuries to patent LIMA or the aorta were
      encountered. CONCLUSIONS: The 3D CT imaging technique is useful in defining the
      optimal surgical strategy for reoperative cardiac surgery. We found that CTA is
      superior to CXR and conventional angiography in defining the position of patent
      grafts and vital structures in relation to the midline and posterior sternum.
      Preoperative mapping of patent coronary grafts and other vital mediastinal
      structures reduces the morbidity of the reoperation through modification of
      surgical approaches.

PMID- 15993622
TI  - Inhaled foreign bodies: management according to early or late presentation.
AB  - OBJECTIVE: This retrospective study aims to compare the early and late clinical
      and management aspects of tracheobronchial aspirated foreign body (AFB), to
      evaluate the factors associated with delayed diagnosis of foreign body aspiration
      (FBA) in children and to compare clinical, radiological and bronchoscopic
      findings in the patients with suspected FBA. A retrospective review of a 10-year
      experience (from 1995 to 2005). A 1512-bed Mansoura University Hospital and 184
      bed Mansoura University Emergency Hospital. METHODS: The medical records of 3300
      patients who underwent bronchoscopy for suspected FBA were reviewed. The data
      were analysed in three groups: the patients with negative bronchoscopy for FBA
      (group I), early (group II) and delayed diagnosis (group III). Foreign body was
      removed using the rigid bronchoscope with or without using the extracting forceps
      (Egyptian novel technique described in the hand made illustration). RESULTS: The
      majority of the patients with FBA were between 3 and 10 years of age. The
      penetration syndrome and decreased breath sounds were determined in a
      significantly higher number of the patients with FBA. The plain chest radiography
      revealed radio-opaque foreign bodies (FBs) in 23.56% of all patients with FBA.
      Pneumonia and atelectasis were significantly more common in the groups with
      negative bronchoscopy and with delayed diagnosis (P<0.01). The FBs were most
      frequently of vegetable origin, such as seeds and peanuts. A significant tissue
      reaction with inflammation and postbronchoscopic complications were more common
      in the delayed cases. The novel technique was used since then in 100 cases
      (4.62%) with a history of FBI (Pins and or small rounded materials). It was
      successful in 73 (73%) cases of non-impacted inhaled pins. Use of forceps was
      needed in 21 (21%) cases. Rebronchoscopy despite using both techniques was needed
      in six (6%) cases within 72h. Failed extraction of the inhaled FB occurred in
      three cases (3%) for whom bronchotomy was needed. CONCLUSIONS: Bronchoscopy is
      indicated on appropriate history and on suspicion. To prevent delayed diagnosis,
      characteristic symptoms, signs and radiological findings of FBA should be checked
      in all suspected cases. As clinical and radiological findings of FBA in delayed
      cases may mimic other disorders, the clinician must be aware of the likelihood of
      FBA.

PMID- 15993623
TI  - Racial and ethnic differences in perinatal mortality: the role of fetal death.
AB  - PURPOSE: We investigate whether variations in infant mortality rates among
      racial/ethnic groups could be explained by variations in fetal mortality rates
      where relatively higher infant mortality rates may correspond to lower fetal
      mortality rates due to possible systematic differences in reporting of fetal
      death compared to live births. METHODS: Using US perinatal data from 1995 to
      1999, we calculated crude mortality rates, birth weight-specific fetal and
      hebdomadal mortality rates, risks of perinatal death, and the risk of being
      classified as a fetal death versus other period death among infants born to Non
      Hispanic White, Non-Hispanic Black, and Hispanic mothers. RESULTS: Two-fold
      disparities between Whites and Blacks persist for all mortality categories. Black
      low birth-weight deliveries, compared to Whites, have perinatal advantages in
      both fetal and hebdomadal periods. Hispanics were less likely than Whites to be
      reported as a fetal versus a hebdomadal death. CONCLUSIONS: While these data
      suggest some underreporting of Black fetal deaths, they provide little evidence
      that Black-White disparities in infant mortality are a function of variations in
      classifying a death occurring at delivery as either a fetal death or as a live
      birth-infant death. These data suggest that the lack of a White-Hispanic
      disparity in fetal mortality rates may be influenced by underreporting.

PMID- 15993624
TI  - Fate of unattended fearful faces in the amygdala is determined by both
      attentional resources and cognitive modulation.
AB  - The evidence for amygdala processing of emotional items outside the focus of
      attention is mixed. We hypothesized that differences in attentional demands may,
      at least in part, explain prior discrepancies. In the present study, attention
      was manipulated by parametrically varying the difficulty of a central task,
      allowing us to compare responses evoked by unattended emotion-laden faces while
      the attentional load of a central task was varied. Reduced responses to
      unattended emotional stimuli may also reflect an active suppression of amygdala
      responses during difficult non-emotional tasks (cognitive modulation). To
      explicitly assess cognitive modulation, an experimental condition was used in
      which subjects performed the central task without the presence of irrelevant
      emotional stimuli. Our findings revealed that amygdala responses were modulated
      by the focus of attention. Stronger responses were evoked during a sex task (when
      faces were attended) relative to a bar-orientation task (when faces were
      unattended). Critically, a valence effect was observed in the right amygdala
      during low attentional demand conditions, but not during medium or high demand
      conditions. Moreover, performing a difficult non-emotional task alone was
      associated with signal decreases in a network of brain regions, including the
      amygdala. Such robust decreases demonstrate that cognitive modulation comprises a
      powerful factor in determining amygdala responses. Collectively, our findings
      reveal that both attentional resources and cognitive modulation govern the fate
      of unattended fearful faces in the amygdala.

PMID- 15993625
TI  - Differential effects of paroxetine on raphe and cortical 5-HT1A binding: a PET
      study in monkeys.
AB  - Positron emission tomography (PET) ligands that are sensitive to transient
      changes in serotonin (5-HT) concentration are desirable for studies of
      neuropsychiatric diseases. Few studies, however, have sought to demonstrate that
      variations in 5-HT concentration can be closely tracked with available
      serotonergic ligands. Microdialysis studies in rats have shown a maximal increase
      in 5-HT concentration in raphe nuclei after systemic infusion of selective
      serotonergic re-uptake inhibitors (SSRIs). We performed PET scans with
      [(18)F]FPWAY, an intermediate-affinity antagonist of 5-HT(1A) receptors, in 4
      anesthetized rhesus monkeys in control studies and after systemic paroxetine
      administration (5 mg/kg, i.v.). In addition, a paired [(11)C]DASB study revealed
      that this paroxetine regimen produced an occupancy of 54-83% of the serotonin
      transporters. According to the conventional receptor competition model, increased
      5-HT concentration produces decreased binding of the radioactive ligand. Over a 3
      h period following paroxetine infusion, a progressively increasing reduction
      (ranging from 8 +/- 6% to 27 +/- 10%) of [(18)F]FPWAY-specific binding was found
      in the raphe nuclei. This result is interpreted as an SSRI-induced increase in 5
      HT concentration, potentially combined with reduced binding to internalized 5
      HT(1A) receptors. In addition, a transient (1 h) increase in cerebral cortical
      binding was observed, attributed primarily to a reduction in cortical 5-HT due to
      the effects of raphe autoreceptor inhibition. This study is the first
      demonstration of the feasibility of quantifying dynamic changes in 5-HT
      neurotransmission in the raphe and the cortex with PET. These results lend
      promise to the use of these serotonergic neuroimaging techniques to study
      neuropsychiatric disorders.

PMID- 15993626
TI  - Association between supine cerebral perfusion and symptomatic orthostatic
      hypotension.
AB  - The goal of this study was to investigate whether the supine resting perfusion of
      brain tissue in symptomatic patients suffering from orthostatic hypotension (OH)
      is changed compared to control subjects and whether an association exists between
      the resting perfusion and the severity of OH. Ten symptomatic OH patients and 8
      control subjects were included in this study. One patient was retrospectively
      excluded because he suffered from multiple system atrophy. Systolic and diastolic
      blood pressure changes were measured during a tilting bed procedure. Cerebral
      blood flow, cerebral blood volume and mean transit time were determined by bolus
      tracking perfusion MRI and correlated with blood pressure changes. Cerebral blood
      volume was significantly increased in OH patients compared with control subjects
      for white matter (P = 0.019) and the mean transit time was significantly
      increased for gray (P = 0.010) and white matter (P = 0.015). The cerebral blood
      flow of the gray (r = 0.74, P = 0.022) and white matter (r = 0.75, P = 0.020) was
      significantly, positively correlated with systolic blood pressure changes. The
      mean transit time in white matter was significantly, negatively correlated with
      systolic blood pressure changes (r = -0.68, P = 0.045). This study suggests that
      in symptomatic patients with OH the cerebral perfusion of the brain in the
      resting, supine position correlates with the severity of OH as measured by
      postural changes in blood pressure.

PMID- 15993627
TI  - Force related activations in rhythmic sequence production.
AB  - Brain imaging studies have implicated the basal ganglia in the scaling of
      movement velocity. Basal ganglia activation has also been reported for movement
      timing. We investigated the neural correlates of scaling of force and time in the
      production of rhythmic motor sequences using functional magnetic resonance
      imaging (fMRI) of the human brain. Participants (N = 13) were imaged while
      squeezing a rigid force transducer in a near isometric manner between thumb and
      index finger, to reproduce four different rhythmic sequences. The responses were
      separated by either equal (600 ms) or alternating (400, 800 ms) intervals, and
      produced with either equal (12 N) or alternating (8, 16 N) forces pulses.
      Intervals and force levels were balanced across each condition. The primary motor
      cortex (M1), supplementary motor area (SMA), basal ganglia, thalamus, and
      cerebellum were activated during the production of sequences marked by equal
      interval and force. There was no reliable main effect of alternating interval. In
      contrast, greater activation of these regions was associated with the extra
      demands of responding with alternating force pulses. We interpret the data as
      identifying a significant role of the BG in the control of force. In addition,
      the results indicate the importance of monitoring force when studying brain
      activation associated with motor timing.

PMID- 15993628
TI  - Feature-based statistical analysis of structural MR data for automatic detection
      of focal cortical dysplastic lesions.
AB  - This paper presents a method for fully automated detection and localization of
      Focal Cortical Dysplastic (FCD) lesions from anatomical magnetic resonance (MR)
      images of the human brain. Model-based tissue classification of the image under
      study was applied first such that a gray matter (GM) segmentation map is obtained
      of which we demonstrate that it also includes possible FCD lesions. Cortical
      thickness was estimated at each voxel using an appropriate distance transform
      applied to the binarized GM object and an FCD specific feature map was
      constructed by computing the ratio of cortical thickness over absolute image
      intensity gradient at each voxel. In absence of any prior anatomical hypothesis
      on the spatial location of the lesion, a statistical parameter map was
      constructed by evaluating the evidence for each gray matter voxel against the
      null hypothesis of no difference in the feature map of the patient versus similar
      maps obtained for a group of normal controls. Voxel clusters for which the null
      hypothesis was found to be improbable at optimally selected thresholds for
      cluster height and extent were reported as lesions. The method was applied to a
      surgical series of 17 FCD patient images that were compared against a group of 64
      neurologically normal controls. The method correctly detected and located the FCD
      lesion in 9 out of 17 FCD cases (53%) using a threshold that minimized false
      positives and 12 of 17 (71%) using a threshold that allowed more false positive
      results. The detected lesions had a median volume of 7.2 cm(3) versus 2.9 cm(3)
      for the non-detected lesions. The detected lesions more often had an increased
      cortical thickness on T1 than the non-detected lesions (P=0.015, Fisher's exact
      test). Due to a high variance of the feature maps in the temporal lobes and
      insula, detection of FCD lesions in these regions appeared more difficult than in
      other brain regions with lower variance.

PMID- 15993629
TI  - Neural mechanisms underlying food motivation in children and adolescents.
AB  - Dramatic increases in childhood obesity necessitate a more complete understanding
      of neural mechanisms of hunger and satiation in pediatric populations. In this
      study, normal weight children and adolescents underwent functional magnetic
      resonance imaging (fMRI) scanning before and after eating a meal. Participants
      showed increased activation to visual food stimuli in the amygdala, medial
      frontal/orbitofrontal cortex, and insula in the pre-meal condition; no regions of
      interest responded in the post-meal condition. These results closely parallel
      previous findings in adults. In addition, we found evidence for habituation to
      food stimuli in the amygdala within the pre-meal session. These findings provide
      evidence that normal patterns of neural activity related to food motivation begin
      in childhood. Results have implications for obese children and adults, who may
      have abnormal hunger and satiation mechanisms.

PMID- 15993630
TI  - Hemispheric specialization of human inferior temporal cortex during coarse-to
      fine and fine-to-coarse analysis of natural visual scenes.
AB  - Recent models of visual recognition have suggested that perceptual analysis may
      start with a parallel extraction of different spatial frequencies (SF), using a
      preferential coarse-to-fine (low-to-high SF) sequence of processing. A rapid
      extraction of low spatial frequency (LSF) information may thus provide an initial
      and crude parsing of the visual scene, subsequently refined by slow but more
      detailed high spatial frequency (HSF) information. However, the sequence of SF
      analysis could be flexible, a high-to-low (HtL) being sometimes preferred to a
      low-to-high (LtH) SF sequence depending on task demands. Furthermore, it has also
      been suggested that the right vs. left hemisphere might be differentially
      specialized in LSF vs. HSF analysis, respectively. By manipulating the temporal
      succession of LSF and HSF stimuli, the present fMRI study investigated whether
      such hemispheric specialization may underlie the flexible use of different time
      course in SF analysis. Participants performed a matching task between two
      successive images of natural scenes (LSF or HSF) that were displayed either in an
      LtH (LSF scene presented first and HSF scene second) or in a reverse HtL
      sequence. A direct inter-hemispheric comparison of the neural responses evoked by
      each SF sequence revealed greater activations within the right occipito-temporal
      cortex for the LtH sequence and within the left occipito-temporal cortex for the
      HtL sequence. These fMRI results suggest that the hemisphere preferentially
      engaged during the sequential processing of different SF might be determined by
      the initial SF-band appearing in this sequence, and that both a coarse-to-fine
      and fine-to-coarse analysis might independently take place in the two
      hemispheres.

PMID- 15993631
TI  - Centrosome inheritance in the male germ line of Drosophila requires hu-li tai
      shao function.
AB  - Cytokinesis partitions a centrosome to each daughter cell at cell division that
      will duplicate and assemble a bipolar spindle in the subsequent M phase.
      Cytokinesis is incomplete in proliferating germ cells in Drosophila and
      cytoplasmic channels connect sibling germ cells. Although centrosomes are
      essential to male fertility, the molecular mechanism that retains centrosomes in
      parental germ cells is not known. Cortical cytoplasmic structures known as
      fusomes extend through ring canals and connect cells within the cyst. Fusome
      assembly in males requires function of hu-li tai-shao (hts), an adducin like
      protein found in fusomes and in the cortical membrane cytoskeleton of somatic
      cells. This work used immunological and cytological methods to place hts mutants
      in an allelic series. Male fertile hts mutants express hts protein and generate
      apparently normal or fragmented fusomes. A male sterile allele does not express
      hts protein or show fusome structures. Gonial cells in all hts mutants showed 2
      centrosomes and mitotic spindles were bipolar. Yet, primary spermatocytes, with
      and without fusome structures, frequently contained too many or too few
      centrosomes. Although spindle structures were not found in spermatocytes without
      centrosomes, meiotic spermatocytes with centrosomes generated bipolar, monopolar,
      and multipolar spindles. Collectively, these results indicate that hts function
      is necessary for centrosome inheritance in spermatocytes as well as for male
      fertility.

PMID- 15993632
TI  - A genome-wide screen for Saccharomyces cerevisiae nonessential genes involved in
      mannosyl phosphate transfer to mannoprotein-linked oligosaccharides.
AB  - A collection of haploid Saccharomyces cerevisiae deletion strains--both MAT a and
      alpha--was screened for mutants that exhibit low dye binding (ldb) phenotype.
      This phenotype has previously been associated with reduced incorporation of
      mannosyl phosphate groups into the mannoprotein-linked oligosaccharides. We
      identified 199 nonessential genes whose deletion resulted in a detectable ldb
      phenotype. They fell into diverse functional categories, including those involved
      in protein glycosylation, vacuolar function, intracellular transport,
      cytoskeleton organization, transcription, signal transduction, among others. The
      study extends the number of known genes that affect mannosyl phosphorylation of
      mannoprotein-linked oligosaccharides, and establishes a link with other relevant
      pathways in the cell, especially vacuolar function. We have assigned an LDB name
      to four uncharacterized ORFs identified in this study: YCL005W, LDB16; YDL146W,
      LDB17; YLL049W, LDB18; and YOR322C, LDB19.

PMID- 15993633
TI  - Enhanced responsiveness to nitric oxide, nitroxyl anions, and nitrergic
      transmitter by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole in the rat
      anococcygeus muscle.
AB  - The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on
      responses to sodium nitroprusside (SNP), S-nitroso-N-acetyl-penicillamine (SNAP),
      the nitroxyl anion donor Angeli's salt, and nitrergic nerve stimulation, as well
      as the release of NO from nitrergic nerves, were studied in the rat isolated
      anococcygeus muscle. YC-1 (1-100 microM) produced concentration-dependent
      relaxations in contracted muscles, which were partially but significantly reduced
      by the inhibitor of soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3,
      a]quinoxalin-1-one (ODQ, 1 and 10 microM). At a concentration that did not affect
      tissue tension, YC-1 (1 microM) significantly enhanced relaxations to SNP, SNAP,
      and Angeli's salt but did not affect relaxations to papaverine (10 microM).
      Nitrergic relaxations elicited by short periods (1 Hz for 10 s, 15 V) and long
      periods of EFS (5 Hz for 5 min, 15 V) were also enhanced by YC-1. YC-1 (100
      microM), in an l-NAME and tetrodotoxin-insensitive manner, also increased the
      amount of NO detected in the organ bath media after the tissue was field
      stimulated (5 Hz for 5 min), which may have resulted from the electrolytic
      degradation of YC-1, as this effect was also seen in the absence of tissue. In
      summary, YC-1 enhanced relaxations to donors of NO, Angeli's salt, and nitrergic
      nerve stimulation in the rat anococcygeus muscle; however, the enhanced release
      of NO by YC-1 following nitrergic nerve stimulation was not a tissue-dependent
      effect.

PMID- 15993634
TI  - Multiple potassium channels mediate nitric oxide-induced inhibition of rat
      vascular smooth muscle cell proliferation.
AB  - Several nitric oxide (NO) effects in the cardiovascular system are mediated by
      soluble guanylate cyclase (sGC) activation but potassium channels (KC) are also
      emerging as important effectors of NO actions. We investigated the relationship
      among vascular smooth muscle cell proliferation, NO, cyclic GMP, and KC using the
      A7r5 smooth muscle cell line derived from rat aorta. NO donors (two
      nitrosothiols, S-nitroso-acetyl-d,l-penicillamine, SNAP, and S-nitroso
      glutathione, GSNO, and an organic nitrate, glyceryl trinitrate, GTN; 1-1000
      microM) dose-dependently inhibited cell proliferation. ODQ (a selective inhibitor
      of sGC; 0.1 and 1 microM) and KT5823 (a selective inhibitor of cGMP-dependent
      protein kinase, 1 microM) prevented NO effects, confirming that sGC is a key
      target. In this report, we show that tetraethylammonium (TEA, a non-selective
      blocker of KC, 300 microM), and 4-aminopyridine (a selective blocker of voltage
      dependent KC, 100 microM) prevented SNAP inhibitory effects on cell
      proliferation, whereas glibenclamide (a selective blocker of ATP-dependent KC, 1
      microM) was ineffective. Iberiotoxin (a selective blocker of high conductance
      calcium-activated KC, 100 nM), as well charybdotoxin (a blocker of high and
      intermediate conductance calcium-activated KC, 100 nM) and apamine (a selective
      blocker of small conductance calcium-activated KC, 100 nM), blocked the
      antiproliferative effect induced by SNAP. NS1619 (an opener of high conductance
      calcium-activated KC, 1-100 microM), inhibited cell proliferation. In addition,
      sub-effective concentrations of ODQ (100 nM) and TEA (10 microM) synergized in
      blocking SNAP antiproliferative effects. Thus, voltage-dependent and calcium
      activated but not ATP-dependent KC appear to have a prominent role, besides sGC
      activation, in NO-induced inhibition of vascular smooth muscle cell
      proliferation.

PMID- 15993635
TI  - Abstracts for the 6th European Paediatric Neurology Society, EPNS Congress, 14-17
      September 2005, Goteborg, Sweden.

PMID- 15993636
TI  - Electron microscopy and microcalorimetry of the postnatal rat heart (Rattus
      norvegicus).
AB  - The interplay of ultrastructure and tissue metabolism was examined in neonatal,
      infant and adult rat hearts by electron microscopy and microcalorimetry.
      Morphometry was used to determine parameters of oxygen diffusion capacity
      (distance between capillaries and mitochondria, capillary surface density) and
      oxidative metabolic capacity (mitochondrial volume fraction). Thin slices and
      large samples of living tissue were examined calorimetrically to quantify aerobic
      metabolism and ischemia tolerance, respectively. After birth, rat hearts grow in
      parallel to body mass and show characteristics of cellular hypertrophy. Capillary
      surface density increases from neonatal to infant rats, and decreases to an
      intermediate value in adult rats. The distance between capillaries and
      mitochondria shows no significant changes throughout postnatal development.
      Mitochondrial volume fraction increases continuously until adulthood. The
      specific aerobic tissue metabolic rate is higher in the neonatal than in the
      infant and adult rat. However, the ischemic decline in metabolic rate is much
      slower in the neonatal rat, reflecting an elevated hypoxia tolerance. In
      conclusion, the neonatal rat heart exhibits a high metabolic rate despite a low
      mitochondrial volume fraction. The subsequent structural rearrangements can be
      interpreted as long-term adaptations to the increased postnatal workload and may
      contribute to the progressive loss of hypoxia tolerance.

PMID- 15993637
TI  - Serum proteins in the leopard seal, Hydrurga leptonyx, in Prydz Bay, Eastern
      Antarctica and the coast of NSW, Australia.
AB  - Blood protein analysis including total serum protein and albumin by chemical
      methods, fibrinogen estimation and serum protein electrophoresis (SPE) was
      performed on the leopard seal, Hydrurga leptonyx. The most commonly observed SPE
      pattern was eight fractions designated albumin, alpha(1a), alpha(1b), alpha(2a),
      alpha(2b), beta(1), beta(2) and gamma-globulin. Significantly higher total serum
      protein and albumin concentrations, as determined by chemical methods, and
      significantly higher alpha(2)-globulin concentrations, determined by SPE, were
      seen in free-ranging male seals compared to females, whilst significantly higher
      beta-globulin concentrations were seen in female seals. Season of sampling
      influenced fibrinogen and beta(2)-globulin concentrations, whereas there were no
      significant differences in any protein concentrations with moult status.
      Qualitative comparison of SPE traces of leopard seals in Antarctica with "sick"
      individuals in NSW, Australia revealed obvious differences, as did quantitative
      comparison of protein concentrations where differences in alpha(1), alpha(2),
      beta(1), beta(2), and gamma-globulin concentrations were seen. These findings
      suggest that SPE is a useful tool for investigating serum proteins in the leopard
      seal, with applications for the investigation of "sick" individuals and the
      assessment of variation in homeostasis. This technique could also be used to
      identify the presence of environmental stressors, subclinical disease and
      physiological variation within specific seal populations.

PMID- 15993638
TI  - Isolation and characterization of hemolymph antifreeze proteins from larvae of
      the longhorn beetle Rhagium inquisitor (L.).
AB  - We describe a simple and effective procedure to isolate antifreeze proteins
      (AFPs) from the hemolymph of larvae of the longhorn beetle Rhagium inquisitor,
      and present some characteristics of their structures. Several AFPs were isolated
      from the hemolymph of this species by heat and acid extraction followed by cation
      exchange. The hemolymph contains at least six AFPs ranging in size from 12.5 to
      12.8 kDa. Of these, three were separated to purity by the ion exchange step, as
      indicated by mass spectrometry. The remaining three forms were further separated
      by size exclusion chromatography, but could not be isolated to purity. All AFPs
      in the hemolymph of this species appears to have isoelectric points above 8.00.
      The dominant form, RiAFP(H4), was purified by the ion exchange step. Its amino
      acid composition reveals a lower level of cysteine and a higher level of
      threonine, arginine, alanine and glycine than seen in other insect AFPs. Its
      trypsin fingerprint does not match that of any known protein. It interacts with
      ice both in the anionic and cationic state.

PMID- 15993639
TI  - Optimization of the sonication extraction method of Hibiscus tiliaceus L.
      flowers.
AB  - The influence of several experimental parameters on the ultrasonic extraction of
      Hibiscus tiliaceus L. flowers were investigated: extraction time, solvent
      polarity, sample amount, solvent volume and sample particle size. It was
      concluded that the most influential variables were extraction time and solvent
      polarity. The optimized procedure employed 5 g of ground flowers, 150 mL of
      methanol and 140 min of extraction. The extracts were fractionated using
      preparative silica columns and the resulting fractions were analyzed by GC/MS.
      Some saturated hydrocarbons, fatty acids, fatty acid methyl esters, phytosterols,
      and vitamin E were identified in the plant extracts.

PMID- 15993640
TI  - High-dose treatment with pergolide in Parkinson's disease patients with motor
      fluctuations and dyskinesias.
AB  - Motor complications arising after long-term treatment with levodopa remain one of
      the main challenges in the treatment of patients with Parkinson's disease (PD).
      Monotherapy with dopamine agonists may delay the onset of motor complications or
      reduce their severity when added to levodopa treatment. Here, we retrospectively
      analyzed data from 62 patients with advanced PD who presented with moderate to
      severe response fluctuations in whom we increased the dose of oral treatment with
      pergolide beyond 4.5mg daily. Patients had been treated with levodopa for 10.7+/
      4.8 years. Pergolide was increased to 8.2+/-4.3 mg per day over a median
      titration period of 13.5 weeks. Mean daily dose of levodopa prior to pergolide
      high-dose treatment was 733+/-468 mg and decreased to 348+/-186 mg after
      pergolide titration. The duration of OFF times decreased from 7.3+/-3.8 to 1.7+/
      0.9 h per day (p < 0.001) measured by patients' diaries. Dyskinesias, present for
      5.0+/-3.3 h per day at baseline, were reduced to 1.4+/-0.8 h per day (p < 0.001)
      and the total daily duration of motor fluctuations (off-time duration plus
      dyskinesia duration) decreased from 10.5+/-7.0 to 2.8+/-2.2 h (p < 0.001). There
      was a significant improvement in parkinsonian symptoms (baseline to endpoint
      reduction of UPDRS III from a median of 36 to 8; p < 0.001). To reduce
      gastrointestinal side effects 23 patients required concomitant treatment with
      domperidone. Seven patients developed hallucinations during the titration period,
      six patients required treatment with clozapine. Our data indicate that increasing
      the dose of pergolide above 5mg per day can dramatically reduce the need for
      levodopa, motor fluctuations and severity of clinical symptoms. Controlled trials
      are needed to further substantiate the efficacy and safety of this treatment
      strategy.

PMID- 15993641
TI  - "An integral part of the children's education": placing sun protection in
      Auckland primary schools.
AB  - Links between ozone depletion, sun exposure and the incidence of melanoma in
      later life have focussed public health attention on risk management, including
      attempts to curtail children's exposure to sunlight. Schools are potentially
      valuable sites in sun protection efforts, as they may combine behavioural
      messages with protective environments. In this paper, we outline the sun-related
      attitudes and policies of a random sample of 20 Auckland primary schools, and
      situate them within the framework of the new public health. We observe that while
      the state requires schools to provide students with a safe environment, there is
      no explicit guidance on what this means in terms of sun protection. Accordingly,
      schools' responses vary according to the perceptions and priorities of individual
      principals. We conclude that while school spaces are being transformed through
      the public health focus on the risks of UV exposure, the neoliberal educational
      landscape in New Zealand appears ambiguous in its support for health promotion.

PMID- 15993642
TI  - Hamstring injury management--Part 2: Treatment.
AB  - The management of hamstring injuries can be described as vexed at best. One
      reason for this may be because of a lack of high-quality research into the
      methods of treatment, rehabilitation and prevention. As a result, an evidence
      based approach to injury management does not exist. Management is based on
      clinical experience, anecdotal evidence and the knowledge of the biological basis
      of tissue repair. Previous hamstring injury is the most recognized risk factor
      for injury, which indicates that treatment approaches may be suboptimal under
      certain conditions. The identification of these risk factors and the methods best
      designed to manage them should be addressed with future research efforts. Much
      anecdotal and indirect evidence exists to suggest that several non-local factors
      contribute to injury. Despite the knowledge that these factors may exist, the
      literature appears almost devoid of research investigating their possible
      identification and treatment. Treatment has traditionally been in the form of
      altering the muscle repair process through the application of electrophysical
      therapy and various soft-tissue-based and exercise-based techniques. Little
      research has investigated the role of other forms of manual therapy particularly
      when directed at non-local structures. This paper will explore and speculate on
      this potential connection and offer some new contributive factors for hamstring
      injury management.

PMID- 15993643
TI  - A versatile vector system for multiple gene expression in plants.
AB  - Today, cloning vectors that have been specifically designed to facilitate the
      fusion, overexpression or down-regulation of a variety of genes in plant cells
      are available from various sources. In most cases, their basic design allows the
      cloning of a single target gene, typically under a specific promoter, in parallel
      with the expression of selection and/or marker genes from the same vector.
      However, new and versatile systems now exist that expand the user's choice to a
      large number of promoters and terminators, and various autofluorescent tags
      confer the ability to express multiple genes from a single transformation vector.

PMID- 15993644
TI  - Parasite immune escape: new views into host-parasite interactions.
AB  - For parasites of humans and animals that rely on vectors or on sexual contact for
      transmission, it is particularly important that infection does not to terminate
      before the occurrence of the crucial event that completes its lifecycle (e.g.
      another mosquito bite). For chronic infection to occur, it is essential that the
      parasite avoids clearance by the host immune system. Much progress has been made
      in elucidating the immunological interactions and the molecular mechanisms
      involved in the process of immune evasion. Mathematical models have also been
      invaluable in understanding these processes, particularly in the generation of
      new ideas about a complex form of immune evasion known as antigenic variation
      whereby a major target of the host immune response is varied during the course of
      a single infection to avoid recognition.

PMID- 15993645
TI  - Fungal evolution: the case of the vanishing mitochondrion.
AB  - Mitochondria, the energy-producing organelles of the eukaryotic cell, are derived
      from an ancient endosymbiotic alpha-Proteobacterium. These organelles contain
      their own genetic system, a remnant of the endosymbiont's genome, which encodes
      only a fraction of the mitochondrial proteome. The majority of mitochondrial
      proteins are translated from nuclear genes and are imported into mitochondria.
      Recent studies of phylogenetically diverse representatives of Fungi reveal that
      their mitochondrial DNAs are among the most highly derived, encoding only a
      limited set of genes. Much of the reduction in the coding content of the
      mitochondrial genome probably occurred early in fungal evolution. Nevertheless,
      genome reduction is an ongoing process. Fungi in the chytridiomycete order
      Neocallimastigales and in the pathogenic Microsporidia have taken mitochondrial
      reduction to the extreme and have permanently lost a mitochondrial genome. These
      organisms have organelles derived from mitochondria that retain traces of their
      mitochondrial ancestry.

PMID- 15993646
TI  - Exploring the ethical issues of the research interview in the cancer context.
AB  - This paper sets out to reflect on ethical issues in the context of a study
      exploring cancer patients', relatives' and nurses' experience of a day hospital
      chemotherapy service. Interviewing can be considered as a well-used approach
      within qualitative methodology, yet little attention has been paid to a many of
      the ethical deliberations that are inherent when adopting this approach,
      particularly in the context of cancer. It is the intention of the authors that
      this paper might raise awareness of these issues, contribute to the ongoing
      debate about conducting research interviews on sensitive topics and provide a
      'real-world' application of these principles. It is considered that the article
      potentially raises more questions that answers and illustrates that there are not
      always quick-fix solutions for the 'real-world' problems qualitative researchers'
      experience.

PMID- 15993647
TI  - To examine the effectiveness of a hospital-based nurse-led secondary prevention
      clinic.
AB  - Modification of cardiovascular risk factors can reduce the incidence of
      myocardial infarction (MI), effectively extend survival, decrease the need for
      interventional procedures, and improve quality of life in persons with known
      cardiovascular disease. Pharmacological treatments and important lifestyle
      changes reduce people's risks substantially (by 1/3 to 2/3) and can slow and
      perhaps reverse progression of established coronary disease. When used
      appropriately, these interventions are more cost-effective than many other
      treatments, currently provided by the National Health Service [Department of
      Health National Service Frameworks: coronary heart disease. Preventing coronary
      heart disease in high risk patients. 2000. HMSO.] Secondary prevention clinics
      are effective means by which to ensure targets are achieved and assist primary
      care in long-term maintenance of lifestyle change and drug optimisation. A 2-year
      hospital-based pilot project was established at the Royal Hospitals, April 2001
      April 2003. The aim of the project was to target patients with coronary heart
      disease, post-MI and/or coronary artery bypass grafting and/or percutaneous
      coronary intervention, 6 months following their cardiac event. The plan was to
      assess patient risk factors and medication a minimum of 6 months following their
      cardiac event to ascertain if government targets were being achieved; secondly,
      to examine the effectiveness of a hospital-based nurse-led secondary prevention
      clinic on modifying risk factors and optimising drug therapies.

PMID- 15993648
TI  - Vascular access complications after cardiac catheterisation: a nurse-led quality
      assurance program.
AB  - BACKGROUND: Vascular access complications may be a cause of discomfort, prolonged
      hospital stay, and impaired outcomes in patients undergoing cardiac
      catheterisation. AIMS: To assess vascular access complication in our patients
      with/without the use of closure devices as a first local benchmark for subsequent
      quality improvement. METHODS: A nurse-led single-centre prospective survey of all
      vascular access complications in consecutive patients submitted to cardiac
      catheterisation during 4 months. RESULTS: The radial and femoral access were used
      in 78 (14%) and 470 (83%), respectively, of 564 procedures, and a closure device
      was used in 136 of the latter. A haematoma (any size) was isolated and uneventful
      in 9.6% of cases. More severe complications (haemoglobin loss >2 g, need for
      blood transfusion or vascular repair) occurred in 1.2% of cases, namely: in none
      of the procedures with radial access, and in 0.4% and 2.4% of femoral diagnostic
      and interventional coronary procedures, respectively. During complicated (n=40)
      vs uncomplicated (n=172) transfemoral interventions, the activated coagulation
      time was 309+/-83 vs 271+/-71 s (p=0.004), but the use of closure devices was
      similar. CONCLUSION: Severe vascular access complications in our patients were
      fewer than in most reports, and virtually absent in radial procedures. Vigorous
      anticoagulation was associated with increased complications in our patients, but
      closure devices were not. A new policy including both the use of the radial
      access whenever possible, and a less aggressive anticoagulation regimen during
      transfemoral interventions will be tested.

PMID- 15993649
TI  - Cyclophilin A may contribute to the inflammatory processes in rheumatoid
      arthritis through induction of matrix degrading enzymes and inflammatory
      cytokines from macrophages.
AB  - Cyclophilin A (CypA) levels increase in the sera and synovial fluids of
      rheumatoid arthritis (RA) patients, but the cell types expressing CypA and the
      function of CypA in the pathogenesis of RA are not known yet.
      Immunohistochemistry analyses revealed high level CypA staining in the
      macrophages in the lining layers of human RA and osteoarthritis synovium. Low
      level CypA staining was also detected in endothelial cells, lymphocytes, and
      smooth muscle cells in RA synovium. Further investigation of the CypA function
      using monocyte/macrophage cell lines revealed that CypA induced expression of
      cytokine/chemokines such as TNF-alpha, IL-8, MCP-1, and IL-1beta and matrix
      metalloproteinase (MMP)-9 through a pathway that is dependent on NFkappaB
      activation. Furthermore, MMP-9 staining pattern overlapped with that of CypA in
      both RA and OA synovium. Our data suggest that CypA may stimulate macrophages to
      degrade joint cartilage via MMP-9 expression and promote inflammation via pro
      inflammatory cytokine secretion.

PMID- 15993650
TI  - The influence of adenovirus fiber structure and function on vector development
      for gene therapy.
AB  - The collective attributes of adenoviruses (Ads), including ease of accomplishing
      replication deficiency, readily achievable high titers, encoding of large
      expression cassettes, efficiency of gene delivery to most cell types, and well
      characterized biology, have made Ads, particularly Ad serotype 5 (Ad 5), some of
      the most utilized vectors for gene delivery. In recent years, however, it has
      become apparent that additional aspects of basic Ad virology must be uncovered
      for this vector system to succeed in the clinic. While local gene delivery is
      generally efficient, the broad tropism of Ad 5 and its tendency to home to the
      liver after systemic administration have proved to be limitations for other
      therapeutic applications, such as the treatment of disseminated cancers and
      cardiovascular disease. This has refocused research into the biology of Ad capsid
      components, particularly the main tropism determinant, the fiber/penton base
      complex, and their influence on transduction of selected cell types in vivo.

PMID- 15993651
TI  - A cDNA encoding diazepam-binding inhibitor/acyl-CoA-binding protein in
      Helicoverpa armigera: molecular characterization and expression analysis
      associated with pupal diapause.
AB  - The diazepam binding inhibitor (DBI) or the acyl-CoA-binding protein (ACBP) is a
      9-10 kDa highly conserved multifunctional protein that plays important roles in
      GABA(A) receptor activity regulation, lipid absorption and steroidogenesis in
      various organisms. To study the functions of DBI/ACBP in insect development or
      diapause, we cloned the cDNA from Helicoverpa armigera (Har) utilizing rapid
      amplification of cDNA ends (RACE). By homology search, Har-DBI/ACBP is conserved
      with the DBI/ACBPs known from other insects. Northern blot analysis showed that
      DBI/ACBP gene expressed in nonneural and neural tissues. RT-PCR combined Southern
      blot analysis revealed that DBI/ACBP mRNA in the brain of nondiapause individual
      was much higher than that in the brain of diapausing insects. At early and middle
      stages of 6th instar larvae, the level of DBI/ACBP mRNA was higher in the midgut
      of diapause type than that in nondiapause type and low at late 6th instar larval
      stage and early pupal stage in both types. In the prothoracic gland (PG),
      DBI/ACBP expression appeared at a high level at middle and late stages of 6th
      larval instar in both nondiapause and diapause types, and declined after
      pupation. In vitro experiments revealed that DBI/ACBP mRNA in PG could be
      stimulated by synthetic H. armigera diapause hormone (Har-DH), suggesting that
      Har-DH may stimulate the PG to produce ecdysteroids by the DBI/ACBP signal
      pathway. By in vitro assay, we also found that FGIN-1-27, which has similar
      functions to DBI/ACBP in ecdysteroidogenesis, could induce PG ecdysteroidogenesis
      effectively, suggesting that DBI/ACBP regulates biosynthesis of ecdysteroids in
      PG. Thus, DBI/ACBP indeed plays a key role in metabolism and development in H.
      armigera.

PMID- 15993652
TI  - Neither panacea nor black box: responding to three Journal of Biomedical
      Informatics papers on computerized physician order entry systems.

PMID- 15993653
TI  - Are certain multicenter randomized clinical trial structures misleading clinical
      and policy decisions?
AB  - Multicenter studies involving randomized clinical trials (RCTs) may have
      different structures. We discuss four general types. The first two, an "ideal"
      multicenter RCT and decentralized multicenter collaborative RCTs, we feel are, in
      different circumstances, highly recommended approaches. The other two, the
      multicenter RCT that ignores site differences and centralized multicenter
      collaborative RCTs, we argue, are not only not cost-effective but may also
      produce misleading results, thus impeding scientific progress and possibly
      putting patients at unnecessary risk.

PMID- 15993654
TI  - Repeated stress and structural plasticity in the brain.
AB  - Although adrenal steroid receptors are distributed widely throughout the central
      nervous system, specific limbic and cortical regions targeted by stress hormones
      play a key role in integrating behavioral and physiological responses during
      stress and adaptation to subsequent stressors. When the stressor is of a
      sufficient magnitude or prolonged, it may result in abnormal changes in brain
      plasticity that, paradoxically, may impair the ability of the brain to
      appropriately regulate and respond to subsequent stressors. Here we review how
      repeated stress produces alterations in brain plasticity in animal models, and
      discuss its relevance to behavioral changes associated with these regions.
      Interestingly, prolonged stress produces opposing effects on structural
      plasticity, notably dendritic atrophy and excitatory synapse loss in the
      hippocampus and prefrontal cortex, and growth of dendrites and spines in the
      amygdala. The granule cells of the dentate gyrus are also significantly affected
      through a decrease in the rate neurogenesis following prolonged stress. How
      functional impairments in these brain regions play a role in stress-related
      mental illnesses is discussed in this context. Finally, we discuss the cumulative
      impact of stress-induced structural plasticity in aging.

PMID- 15993655
TI  - Inverted appendix mistaken for a polyp during colonoscopy and leading to
      intussusception.
AB  - A spectrum of appendiceal diseases, ranging from simple mucous distension to
      acute perforated appendicitis, are seen in patients with CF. We report a 6 year
      old boy with CF and recurrent periumbilical pain. During colonoscopy, a fleshy
      pedunculated mass at the junction of the ascending colon and caecum was mistaken
      for a polyp and excised. However, histopathological examination suggested it was
      a segment of inverted appendix. The remnant of the inverted appendix was
      subsequently found to be associated with an intussusception.

PMID- 15993656
TI  - Laryngeal water receptors are insensitive to body temperature in neonatal
      piglets.
AB  - Heat stress and the laryngeal chemoreflex (LCR) have both been implicated as
      possible contributors to the sudden infant death syndrome (SIDS). We recently
      reported that moderate hyperthermia, induced in decerebrate piglets by external
      heating, substantially prolonged the LCR elicited by injecting 0.1 ml of water
      into the larynx through a prepositioned transnasal catheter. To examine the
      question of whether hyperthermia influences the responses of laryngeal water
      receptors, we recorded single fiber action potentials in fine strands of the
      superior laryngeal nerve (SLN) in decerebrate piglets while the larynx was filled
      with water or isotonic saline. Water receptors, identified by their much brisker
      response to water than to saline, were studied with body temperature at 37.9+/
      0.2 degrees C, after warming the animal to 40.6+/-0.2 degrees C and after cooling
      back to 37.7+/-0.3 degrees C. The results show no effect of body temperature
      change, in this range, on the responses of the laryngeal water receptors and thus
      suggest that the potentiation of the LCR by hyperthermia is mediated by a central
      action.

PMID- 15993657
TI  - Gas mixing efficiency from birth to adulthood measured by multiple-breath
      washout.
AB  - Efficient mixing of inspired gas with the resident gas of the lung is an
      essential requirement of effective respiration. This review focuses on one method
      for quantifying ventilation inhomogeneity: the multiple-breath inert gas washout
      (MBW). MBW has been employed as a research tool in adults and school age children
      for more than 50 years. Modifications allowing data collection in infants and
      preschoolers have been described recently. Indices of overall ventilation
      inhomogeneity, such as the lung clearance index and moment ratios, are raised in
      many infants with lung disease of prematurity, and in young children with cystic
      fibrosis. These indices may be more sensitive than other lung function measures
      for the early detection of airway disease. We describe, for the first time, a
      development of the MBW analysis that allows calculation of acinar and conductive
      zone inhomogeneity indices in spontaneously breathing children. Although
      methodological and analytical issues remain, the future clinical and research
      applications of MBW justify accelerated research in this field.

PMID- 15993658
TI  - Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep
      apnea.
AB  - We hypothesized that neural processes mediating deficient sensory and autonomic
      regulatory mechanisms in obstructive sleep apnea (OSA) would be revealed by
      responses to inspiratory loading in brain regions regulating sensory and motor
      control. Functional magnetic resonance imaging (fMRI) signals and physiologic
      changes were assessed during baseline and inspiratory loading in 7 OSA patients
      and 11 controls, all male and medication-free. Heart rate increases to
      inspiratory loading began earlier and load pressures were achieved later in OSA
      patients. Comparable fMRI changes emerged in multiple brain regions in both
      groups, including limbic, cerebellar, midbrain, and primary motor cortex.
      However, in OSA subjects, altered signals appeared in primary sensory thalamus
      and sensory cortex, supplementary motor cortex, cerebellar cortex and deep
      nuclei, cingulate, medial temporal, and insular cortices, right hippocampus, and
      midbrain. Signal delays occurred in basal ganglia. We conclude that areas
      mediating sensory and autonomic processes, and motor timing, are affected in OSA;
      many of these areas overlap regions of previously demonstrated gray matter loss.

PMID- 15993659
TI  - Foreword.

PMID- 15993660
TI  - Simultaneous analysis of insect repellent DEET, sunscreen oxybenzone and five
      relevant metabolites by reversed-phase HPLC with UV detection: application to an
      in vivo study in a piglet model.
AB  - N,N-Diethyl-m-toluamide (DEET) and oxybenzone are two essential active
      ingredients in insect repellent and sunscreen preparations. We developed and
      validated a simple, sensitive, and selective HPLC assay to simultaneously measure
      DEET, oxybenzone and five primary metabolites of DEET and oxybenzone in
      biological samples including plasma, urine and skin strips. The compounds were
      separated on a reversed-phase C18 column using three-stage gradient steps with
      methanol and water. DEET and two relevant metabolites were detected at 254 nm,
      while oxybenzone and three relevant metabolites were detected at 289 nm. The
      limit of detection was 0.6 ng for DEET and 0.5 ng for oxybenzone, respectively.
      The developed method was further applied to analyze various biological samples
      from an in vivo animal study that evaluated concurrent use of commercially
      available insect repellent and sunscreen preparations.

PMID- 15993661
TI  - Simultaneous analysis of thebaine, 6-MAM and six abused opiates in postmortem
      fluids and tissues using Zymark automated solid-phase extraction and gas
      chromatography-mass spectrometry.
AB  - Opiates are some of the most widely prescribed drugs in America and are often
      abused. Demonstrating the presence or absence of opiate compounds in postmortem
      fluids and/or tissues derived from fatal civil aviation accidents can have
      serious legal consequences and may help determine the cause of impairment and/or
      death. However, the consumption of poppy seed products can result in a positive
      opiate drug test. We have developed a simple method for the simultaneous
      determination of eight opiate compounds from one extraction. These compounds are
      hydrocodone, dihydrocodeine, codeine, oxycodone, hydromorphone, 6
      monoacetylmorphine, morphine, and thebaine. The inclusion of thebaine is notable
      as it is an indicator of poppy seed consumption and may help explain
      morphine/codeine positives in cases where no opiate use was indicated. This
      method incorporates a Zymark RapidTracetrade mark automated solid-phase
      extraction system, gas chromatography/mass spectrometry, and trimethyl silane
      (TMS) and oxime-TMS derivatives. The limits of detection ranged from 0.78 to 12.5
      ng/mL. The linear dynamic range for most analytes was 6.25-1600 ng/mL. The
      extraction efficiencies ranged from 70 to 103%. We applied this method to eight
      separate aviation fatalities where opiate compounds had previously been detected.

PMID- 15993662
TI  - Application of solid phase extraction and high-performance liquid chromatography
      to qualitative and quantitative analysis of nucleotides and nucleosides in human
      cerebrospinal fluid.
AB  - New method of qualitative and quantitative analysis of nucleotides in human
      cerebrospinal fluid (CSF), based on the combination of extraction of purines and
      pyrimidines to the solid phase (SPE) and high-performance liquid chromatography
      (HPLC), was proposed. Use of SPE and lyophilization of samples allowed for the
      first time to detect the presence of di- and triphosphonucleotides in human CSF.
      Concentration of those compounds varied from 0.003 to 5.0 microM. Differences in
      the nucleotide mixture composition in human CSF detected with the new method are
      coupled with the neurological disorders and might be a basis for an efficient
      diagnostic tool.

PMID- 15993663
TI  - A highly sensitive LC-MS-MS assay for analysis of midazolam and its major
      metabolite in human plasma: applications to drug metabolism.
AB  - The present report describes a rapid, selective and a highly sensitive assay for
      midazolam (MDZ) and its major metabolite 1-hydroxymidazolam (1-OH-MDZ) in human
      plasma employing liquid chromatography-tandem mass spectrometry (LC-MS-MS)
      detection. The method involves liquid-liquid extraction sample clean-up,
      separation on a Purospher RP 18-e column and detection with an electrospray
      interface in the positive ion mode. The overall recoveries were about 100% and
      80% for midazolam and 1-hydroxymidazolam, respectively. Accuracy, precision and
      linearity were acceptable for biological samples with quantitation limits of 0.1
      100 ng mL(-1) plasma for both analytes. The validated method was successfully
      applied to quantify plasma concentration of midazolam and 1-hydroxymidazolam in
      authentic samples from a healthy volunteer following a single 15 mg oral dose of
      midazolam (apparent total clearance: 3.47 L h(-1)kg(-1) and AUC(0-alpha)IOH
      MDZ/MDZ: 0.338).

PMID- 15993664
TI  - Merits of HPLC-based method over spectrophotometric method for assessing the
      kinetics and inhibition of mammalian adenosine deaminase.
AB  - Measurement of adenosine deaminase (ADA) activity using spectrophotometric method
      presents problem, regarding the quantitative estimation of the substrate
      degradation and product formation, due to the closely apposed lambda(max) of the
      substrates, product and the inhibitor. The feasibility of applying reverse-phase
      HPLC technique, for studying adenosine deaminase-catalyzed reaction product and
      inhibition study was examined. We have drawn a comparison between the HPLC-based
      method over the corresponding spectrophotometric method. A gradient elution
      pattern was used to separate substrate (adenosine and deoxyadenosine), product
      (inosine and deoxyinosine) and standard adenosine deaminase inhibitor (erythro-9
      (3-nonyl-p-aminobenzyl)-adenine) in the HPLC method. The product formation was
      quantitated by monitoring the absorbance at 260 nm with the progress of time. The
      limit of detection as well as the limit of quantification of the respective
      enzymatic product were found to be in nano molar (nM) range in the HPLC method.
      This study was also extended to monitor adenosine deaminase activity in different
      cancer cells of hematological origin. The HPLC-based method is found to be
      suitable for the quantitative estimation of adenosine deaminase-catalyzed
      reaction product and for studying inhibition mechanism of different inhibitors.
      The HPLC-based method has specific advantages over the spectrophotometric method.
      Moreover, the concentration of different nucleotides in cell lysate and body
      fluid can be measured using this HPLC method.

PMID- 15993665
TI  - Differentiation between Candida species isolated from diabetic foot by fatty acid
      methyl ester analysis using gas chromatography.
AB  - Gas chromatography (GC) was used to differentiate 100 isolates of Candida species
      (Candida parapsilosis, Candida albicans, Candida tropicalis, Candida famata and
      Candida glabrata) from 22 of 509 diabetic patients in whom the same species had
      been isolated from ulcer and interdigital spaces of the same and/or the other
      foot. All clinical isolates were identified by quantitative differences in the
      composition of six cell fatty acids (CFA). The values of the coefficients of
      variability (CV) of CFA show that the isolates from foot ulcers and interdigital
      spaces of the same diabetic patient probably belong to different chemotypes of
      the same Candida species.

PMID- 15993666
TI  - Growth of Estonian seventeen-year-old boys during the last two centuries.
AB  - Between 1811 and 2003, the mean height of 17-year-old Estonian boys increased
      18.4 cm (0.97 cm per decade). The increase was 5.2 cm (0.7 cm per decade) between
      1811 and 1886, 12.3 cm (2.2 cm per decade) between 1922 and 1978, and 0.5 cm per
      decade between 1978 and 2003. Between 1922 and 2003, mean height increased 8.2%
      and mean weight increased 27.2%. Between 1956 and 2003, biacromial (shoulder)
      breadth increased more than bicristal (hip) breadth; relative chest depth
      diminished; chest circumference and upper thigh circumference both increased. A
      multidimensional body structure model is constructed from 1998 to 2003 data.

PMID- 15993667
TI  - Differential brain growth in the infant born preterm: current knowledge and
      future developments from brain imaging.
AB  - Preterm birth is associated with a high prevalence of neuropsychiatric impairment
      in childhood and adolescence, but the neural correlates underlying these
      disorders are not fully understood. Quantitative magnetic resonance imaging
      techniques have been used to investigate subtle differences in cerebral growth
      and development among children and adolescents born preterm or with very low
      birth weight. Diffusion tensor imaging and computer-assisted morphometric
      techniques (including voxel-based morphometry and deformation-based morphometry)
      have identified abnormalities in tissue microstructure and cerebral morphology
      among survivors of preterm birth at different ages, and some of these alterations
      have specific functional correlates. This chapter reviews the literature
      reporting differential brain development following preterm birth, with emphasis
      on the morphological changes that correlate with neuropsychiatric impairment.

PMID- 15993668
TI  - Novel algorithm detecting trabecular termini in muCT and MRI images.
AB  - In this paper, a novel algorithm detecting trabecular termini in three
      dimensional images of trabecular bone is introduced. The algorithm is applied to
      the analysis of muCT and MRI images of distal radius trabecular bone samples. In
      muCT images, the volume of the trabecular termini constitutes at most 2.1% of the
      bone volume fraction BV/TV and is typically smaller than 1% of BV/TV. Isolated
      trabeculae are not observed in the interior of the trabecular bone samples.
      Trabecular bone structure assessed with muCT appears thus highly optimized. The
      volume and the number of the trabecular termini do not correlate with BV/TV.
      These quantities do not correlate also with apparent Young's modulus of the
      samples. In contrast in MRI images, segmented with the dual reference limit
      method, the volume of the trabecular termini and the volume of isolated parts
      constitute even up to 14% of the apparent bone volume fraction App.BV/TV. For MRI
      images, the volume of the trabecular termini increases significantly with
      decreasing App.BV/TV. The volume and the number of the trabecular termini,
      derived from MRI images do not correlate with Young's modulus. There is also no
      correlation between the number and the volume of the trabecular termini,
      estimated from MRI and muCT images. The volume of the trabecular termini is
      overestimated 15 times in MRI images. App.BV/TV correlates strongly with BV/TV.
      Young's modulus derived from MRI images correlates strongly with Young's modulus
      found for muCT data. It is shown that the diagnostic significance of latter
      result is highly limited.

PMID- 15993669
TI  - Reduced bone mineral density in male Severe Acute Respiratory Syndrome (SARS)
      patients in Hong Kong.
AB  - During the Severe Acute Respiratory Syndrome (SARS) outbreak in Hong Kong in
      2003, patients were treated with very high doses of corticosteroid and ribavirin.
      The detrimental effects of such treatment on the bone mineral density (BMD) of
      SARS patients are unknown. To compare the BMD of SARS patients with normal range
      data, a cross-sectional survey was conducted. The bone mineral density of 224
      patients with SARS, who were treated with an average of 2753 mg (SD = 2152 mg)
      prednisolone and 29,344 mg (SD = 15,849 mg) of ribavirin was compared to normal
      data. Six percent of men had a hip BMD Z score of < or =-2 (P = 0.057 for testing
      the hypothesis that >2.5% of subjects should have a Z score of < or =-2).
      Moreover, there was a negative association (r = -0.25, P = 0.023) between the
      duration of steroid therapy and BMD in men. We conclude that male SARS patients
      had lower BMD at the hip than normal controls, and this could be attributed to
      prolonged steroid therapy.

PMID- 15993670
TI  - Expression of mouse HtrA1 serine protease in normal bone and cartilage and its
      upregulation in joint cartilage damaged by experimental arthritis.
AB  - Levels of HtrA1 protein in cartilage have been reported to elevate in joints of
      human osteoarthritis patients. To understand roles of HtrA1 in normal
      osteogenesis as well as in pathogenesis of arthritis, we examine HtrA1 expression
      pattern during bone and cartilage development and in articular cartilage affected
      by experimental arthritis. HtrA1 is not expressed in mesenchymal or cartilage
      condensations before initiation of ossification. When ossification begins in the
      condensations, the expression of HtrA1 starts in chondrocytes undergoing
      hypertrophic differentiation near the ossification center. Hypertrophic
      chondrocytes found in adult articular cartilage and epiphyseal growth plates also
      express HtrA1. When arthritis is induced by injection of anti-collagen antibodies
      and lipopolysaccharide, resting chondrocytes proceed to terminal hypertrophic
      differentiation and start expressing HtrA1. These data suggest that hypertrophic
      change induces HtrA1 expression in chondrocytes both in normal and pathological
      conditions. HtrA1 has been reported to inhibit TGF-beta signaling. We show that
      HtrA1 digests major components of cartilage, such as aggrecan, decorin,
      fibromodulin, and soluble type II collagen. HtrA1 may, therefore, promote
      degeneration of cartilage by inducing terminal hypertrophic chondrocyte
      differentiation and by digesting cartilage matrix though its TGF-beta inhibitory
      activity and protease activity, respectively. In bone, active cuboidal
      osteoblasts barely express HtrA1, but osteoblasts which flatten and adhere to the
      bone matrix and osteocytes embedded in bone are strongly positive for HtrA1
      production. The bone matrix shows a high level of HtrA1 protein deposition akin
      to that of TGF-beta, suggesting a close functional interaction between TGF-beta
      and HtrA1.

PMID- 15993671
TI  - A clinician's guide to the appropriate and accurate use of antibiotics: the
      Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria.
AB  - In response to the overuse and misuse of antibiotics, leading to increasing
      bacterial resistance and decreasing development of new antibiotics, the Council
      for Appropriate and Rational Antibiotic Therapy (CARAT) has developed criteria to
      guide appropriate and accurate antibiotic selection. The criteria, which are
      aimed at optimizing antibiotic therapy, include evidence-based results,
      therapeutic benefits, safety, optimal drug for the optimal duration, and cost
      effectiveness.

PMID- 15993672
TI  - Rational antibiotic treatment of outpatient genitourinary infections in a
      changing environment.
AB  - In the outpatient setting, genitourinary infections (GUIs) remain costly to treat
      and are a significant cause of morbidity. Recent evidence supports more
      substantial roles for pathogens other than Escherichia coli, particularly gram
      positive pathogens, in the pathogenesis of GUIs. Broad-spectrum agents should be
      considered in order to address this etiologic change appropriately. Criteria for
      antimicrobial selection set forth by the Council for Appropriate and Rational
      Antibiotic Therapy (CARAT) recommend using antibiotics that are supported by
      strong clinical evidence, have good susceptibility profiles, are safe, are cost
      effective, and are used for the optimal duration. Evidence-based guidelines
      recommend considering local E coli resistance rates to trimethoprim
      sulfamethoxazole and using fluoroquinolones as second-line therapy when
      resistance is high. Fluoroquinolones are recommended for the treatment of
      pyelonephritis and prostatitis. Among the fluoroquinolones, levofloxacin and
      gatifloxacin offer coverage for the gram-negative and gram-positive pathogens,
      which may make them preferable in treating urinary tract infections empirically
      in such patient groups. For the treatment of bacterial prostatitis, only
      trimethoprim and the fluoroquinolones possess both the appropriate bactericidal
      activity and the ability to diffuse into the prostate. Levofloxacin shows
      particularly good penetration into prostatic tissue. Safety issues to consider
      include imbalances in intestinal microflora caused by antimicrobial agents that
      may lead to overgrowth of vancomycin-resistant enterococci and Clostridium
      difficile-associated diarrhea. Once the optimal agent is identified, the optimal
      duration of treatment should be determined to maximize treatment success while
      minimizing the potential for resistance. Finally, cost considerations include the
      costs of treatment failure due to inappropriate therapy or nonadherence to the
      therapeutic regimen.

PMID- 15993673
TI  - Appropriate antibiotic treatment of genitourinary infections in hospitalized
      patients.
AB  - The etiology of urinary tract infections (UTIs) that require hospitalization,
      whether they originate in the hospital or in the community, is changing, with
      increasing findings of gram-positive organisms. The Council for Appropriate and
      Rational Antibiotic Therapy (CARAT) criteria recommend evaluating treatment
      choices on the basis of sound clinical evidence, potential for therapeutic
      benefits, safety, optimal duration of treatment, and cost-efficacy in order to
      improve antibiotic treatment. Evidence-based guidelines recommend
      fluoroquinolones for the treatment of patients with cases of pyelonephritis or
      bacterial prostatitis severe enough to warrant hospitalization. For other serious
      UTIs, fluoroquinolones are usually recommended either when traditional agents
      have failed or when resistance to traditional agents is high. Even in the context
      of rapidly changing antimicrobial resistance patterns, the fluoroquinolones have
      maintained consistent, well-tolerated efficacy against many of the principal
      organisms responsible for UTIs, and are generally considered safe for most
      patients. To increase the likelihood of treatment success with first-line
      therapy, an antimicrobial agent must attain sufficient concentrations in the
      target tissue or in the urine for an appropriate amount of time. Both
      levofloxacin and gatifloxacin are excreted unchanged in the urine in
      concentrations that far exceed the minimum inhibitory concentration of most
      uropathogens. Factors that affect cost-effectiveness that should be considered
      include acquisition costs as well as treatment success and ease of use for
      hospital staff.

PMID- 15993674
TI  - Principles of antibiotic treatment of community-acquired pneumonia in the
      outpatient setting.
AB  - Community-acquired pneumonia (CAP) is a common illness with high rates of
      morbidity and mortality. Nearly 80% of the treatment for this condition is
      provided in the outpatient setting. Among the etiologic agents associated with
      bacterial CAP, the predominant pathogen is Streptococcus pneumoniae. Treatment of
      CAP for the most part is empirical; therefore, any antibiotic treatment should
      cover both typical and atypical pathogens. The beta-lactams have historically
      been considered standard therapy for the treatment of CAP. However, the impact of
      rising resistance rates is now a primary concern facing physicians. For patients
      with comorbidities or recent antibiotic therapy, current guidelines recommend
      either combination therapy with a beta-lactam and a macrolide or an
      antipneumococcal fluoroquinolone alone. Fluoroquinolones are broad-spectrum
      antibiotics that exhibit high levels of penetration into the lungs and low levels
      of resistance. Evidence from clinical trials indicates clinical success rates of
      > 90% for moxifloxacin, gatifloxacin, and levofloxacin in the treatment of CAP
      due to S pneumoniae. Data from comparative clinical trials suggest
      fluoroquinolone monotherapy is as efficacious as beta-lactam-macrolide
      combination therapy in the treatment of CAP patients. The respiratory
      fluoroquinolone levofloxacin has also been shown to be effective in CAP patients
      for the treatment of macrolide-resistant S pneumoniae. The use of azithromycin,
      telithromycin, and fluoroquinolones in short-course regimens has been shown to be
      efficacious, safe, and tolerable in patients with CAP. Based on clinical
      evidence, high-dose, short-course therapies may represent a significant advance
      in the management of CAP.

PMID- 15993675
TI  - Antimicrobial treatment of lower respiratory tract infections in the hospital
      setting.
AB  - Respiratory tract infections (RTIs) that may require hospitalization include
      acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia
      (CAP), and hospital-acquired pneumonia (HAP), which includes ventilator
      associated pneumonia (VAP). Healthcare-associated pneumonia (HCAP) is treated
      similar to HAP and may be considered with HAP. For CAP requiring hospitalization,
      the current guidelines for the treatments of RTIs generally recommend either a
      beta-lactam and macrolide combination or a fluoroquinolone. The respiratory
      fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin) are
      excellent antibiotics due to high levels of susceptibility among gram-negative,
      gram-positive, and atypical pathogens. The fluoroquinolones are active against >
      98% of Streptococcus pneumoniae, including penicillin-resistant strains.
      Fluoroquinolones are also recommended for AECB requiring hospitalization.
      Evidence from clinical trials suggests that levofloxacin monotherapy is as
      efficacious as combination ceftriaxone-erythromycin therapy in the treatment of
      patients hospitalized with CAP. For early-onset HAP, VAP, and HCAP without the
      risk of multidrug resistance, ceftriaxone, ampicillin-sulbactam, ertapenem, or
      one of the fluoroquinolones is recommended. High-dose, short-course therapy
      regimens may offer improved treatment due to higher drug concentrations, more
      rapid killing, increased adherence, and the potential to reduce development of
      resistance. Recent studies have shown that short-course therapy with
      levofloxacin, azithromycin, or telithromycin in patients with CAP was effective,
      safe, and tolerable and may control the rate of resistance.

PMID- 15993676
TI  - Appropriate outpatient treatment of acute bacterial exacerbations of chronic
      bronchitis.
AB  - Acute exacerbations of chronic bronchitis (AECB), which are characteristic of
      chronic obstructive pulmonary disease (COPD), contribute to morbidity and
      decreased quality of life for patients with COPD. A significant proportion of
      these exacerbations are due to bacterial infections. The Council for Appropriate
      and Rational Antibiotic Therapy (CARAT) criteria provide guidance for choosing
      the optimal drug at its optimal dose and duration for antimicrobial treatment of
      AECB due to bacterial infection. Evidence-based guidelines recommend stratifying
      patients according to risk factors to improve selection of targeted antimicrobial
      therapy. With increasing rates of resistance to some antimicrobials, resistance
      is also an important consideration for reducing treatment failures and decreasing
      the need for further pharmacologic treatment. Fluoroquinolones are recommended as
      first-line therapy for patients with chronic bronchitis who have risk factors;
      gatifloxacin, gemifloxacin, and levofloxacin are highly active against commonly
      encountered pathogens. Safety profiles are an important consideration because
      adverse events and poor tolerability can reduce patient adherence rates, which in
      turn can lead to poorer outcomes. Safety profiles also become an important
      consideration as shorter-course, higher-dose therapies become more prevalent.
      First-line therapy with a well-tolerated antibiotic that is active against the
      predominant pathogens, combined with low resistance rates and a convenient once-a
      day dosing regimen, may reduce overall costs. Fluoroquinolones exhibit low
      resistance, good activity levels, and high respiratory penetration, and they are
      particularly well suited for shorter-course, higher-dose regimens in selected
      patients. Shorter-course, higher dose regimens, in turn, may be more effective,
      cost-efficient, and appropriate for controlling the rise of resistance than
      standard regimens.

PMID- 15993677
TI  - Treatment of rhinosinusitis in the outpatient setting.
AB  - Rhinosinusitis is one of the most common respiratory tract conditions seen by
      primary care physicians. Each year approximately 20 million cases of acute
      bacterial rhinosinusitis (ABRS) occur in the United States. Since diagnosis of
      ABRS relies on clinical evaluation, treatments are usually empirical and include
      an antibiotic treatment that covers the common bacteria associated with ABRS
      infection, Streptococcus pneumoniae and Haemophilus influenzae. The Council for
      Appropriate and Rational Antibiotic Therapy (CARAT) recommends that antimicrobial
      therapy for rhinosinusitis should combine high susceptibility, clinical
      effectiveness, safety, and tolerability. The most efficacious antibiotics for
      ABRS include the respiratory fluoroquinolones gatifloxacin, levofloxacin, and
      moxifloxacin, as well as ceftriaxone and amoxicillin-clavulanate. The use of
      fluoroquinolones or high-dose amoxicillin-clavulanate is recommended for patients
      with mild disease who have had recent antimicrobial therapy or for patients with
      moderate disease. These drugs are generally well tolerated with mild adverse
      effects. Resistance to fluoroquinolones in S pneumoniae and H influenzae has
      remained low in spite of their increased use. Recent studies indicate that short
      course, high-dose treatment regimens may reduce total drug use, improve
      tolerability and adherence, prevent increases in resistance, and increase
      efficacy. The use of fluoroquinolones or amoxicillin-clavulanate in a short
      course, high-dose regimen may represent an exciting new protocol in the treatment
      of rhinosinusitis.

PMID- 15993678
TI  - Background and threshold: critical comparison of methods of determination.
AB  - Different procedures to identify data outliers in geochemical data are reviewed
      and tested. The calculation of [mean+/-2 standard deviation (sdev)] to estimate
      threshold values dividing background data from anomalies, still used almost 50
      years after its introduction, delivers arbitrary estimates. The boxplot,
      [median+/-2 median absolute deviation (MAD)] and empirical cumulative
      distribution functions are better suited for assisting in the estimation of
      threshold values and the range of background data. However, all of these can lead
      to different estimates of threshold. Graphical inspection of the empirical data
      distribution using a variety of different tools from exploratory data analysis is
      thus essential prior to estimating threshold values or defining background. There
      is no good reason to continue to use the [mean+/-2 sdev] rule, originally
      proposed as a 'filter' to identify approximately 2(1/2)% of the data at each
      extreme for further inspection at a time when computers to do the drudgery of
      numerical operations were not widely available and no other practical methods
      existed. Graphical inspection using statistical and geographical displays to
      isolate sets of background data is far better suited for estimating the range of
      background variation and thresholds, action levels (e.g., maximum admissible
      concentrations--MAC values) or clean-up goals in environmental legislation.

PMID- 15993679
TI  - Development of a dynamic strategy planning theory and system for sustainable
      river basin land use management.
AB  - Land use management is central to government planning for sustainable
      development. The main purpose of this study is to develop a novel strategy
      planning theory and system to assist responsible authorities in obtaining
      alternatives of sustainable top river basin land use management. The concepts and
      theory of system analysis, driving force-state-response (DSR) framework, and
      system dynamics are used to establish the DSR dynamic strategy planning procedure
      in this work. The integrated management of the land, water, and air resources of
      a river basin system is considered in the procedure. Two modified land use
      management procedures combined with the DSR dynamic strategy planning procedure
      are developed in this work. Based on the DSR dynamic strategy planning procedure,
      the sustainable river basin land use management DSR dynamic decision support
      system (SRBLUM-DSRD-DSS) is developed by using the Vensim, MS Excel, ArcView, and
      Visual Basic software. The concepts of object-orientation are used to develop the
      system dynamic optimization and simulation models of SRBLUM-DSRD-DSS. Based on
      the modified land use management procedures, SRBLUM-DSRD-DSS is used to assist
      decision makers in generating the land use plans of the Nankan river basin in
      Taoyuan County of Taiwan. Since the decisions of land, water and air resources
      management are still made at different agencies, the land use management system
      should be modified based on the innovational procedure to implement the
      management strategy developed in this work. The results show that the modified
      land use management procedures can be a guidance for the governments in modifying
      the systems and regulation of urban and regional plans in Taiwan.

PMID- 15993680
TI  - Bootstrap hypothesis testing and power analysis at low dose levels.
AB  - This study demonstrates the variability in dose estimates using the nonparametric
      bootstrap to estimate the variability in the mean dose when mean values from
      environmental data are used in the dose calculation. Bootstrap hypothesis testing
      and power analysis are demonstrated. For the data set shown here, the normal
      assumption works well if the environmental data can be considered fixed, known
      constants. However, when there exists a good deal of variability in the
      environmental data, as is most often the case, or where scarce data are
      available, making a normal assumption leads to gross underestimation of the
      variability in the mean dose.

PMID- 15993681
TI  - Environmental exposure to lead and its correlation with biochemical indices in
      children.
AB  - Lead is a global concern because of its ubiquity in the environment and known to
      be associated with abnormal neurobehavioral and cognitive development of young
      children. There is no study from India to describe a composite profile of blood
      lead and its biochemical influences in children. The present study was aimed at
      determining the proportion of children with >10 mug/dL blood lead levels (BLLs),
      association between BLLs, and sociodemographic characteristics, if any, and
      alterations in biochemical indices in the blood as an underlying mechanism of
      lead intoxication. A total of 62 children (4--12 y) of Lucknow and nearby areas
      were recruited to determine BLLs, delta-amimolevulinic acid dehydratase (delta
      ALAD) activity, catalase (CAT) activity, and malondialdehyde (MDA) and
      glutathione (GSH) levels in the blood. Mean level of blood lead was 7.47+/-3.06
      microg/dL (2.78--15.0) and 29%-exceeded 10 microg/dL, CDC intervention level. The
      BLLs were found to be significantly influenced by social status, area of
      residence, source of water supply, maternal educational status (p<0.001), type of
      house, and proximity to traffic density (p<0.01). delta-ALAD was significantly
      lower in the group of children with BLLs 11.39+/-1.39 microg/dL when compared to
      children with BLLs 7.11+/-1.25 microg/dL and 3.93+/-0.61 microg/dL (p=0.0007,
      0.0005, respectively). However, CAT activity was higher in the groups of children
      with higher blood levels than with lower BLLs (p=0.0159, 0.0001, respectively).
      There was an increase in MDA level with a concomitant decrease of GSH in children
      with BLLs 11.39+/-1.39 microg/dL compared with those of children with BLLs 7.11+/
      1.25 microg/dL and 3.93+/-0.61 microg/dL (p=0.0001, 0.0002, and p=0.0001,
      respectively). There was statistically significant correlation of BLLs with delta
      ALAD (r=-0.44, p=0.00035), MDA (r=0.46, p=0.00018), GSH (r=-0.62, p=0.00001), and
      CAT (r=0.44, p=0.00035). Significantly, CAT activity, MDA, and GSH levels were in
      turn, found to be correlated with delta-ALAD (r=-0.45, p=0.00024; r=-0.43,
      p=0.00053; r=0.43, p=0.00053, respectively). Results of the present study
      indicate a declining trend of BLLs in children when compared with those reported
      from metropolitan cities of India when leaded gasoline was in practice and that
      the BLLs were significantly associated with biochemical indices in the blood
      which have the potential to be used as biomarkers of lead intoxication.

PMID- 15993682
TI  - The impact of the hyperacid Ijen Crater Lake: risks of excess fluoride to human
      health.
AB  - The Asembagus irrigation area (East Java, Indonesia) receives a high input of
      fluoride (F) via surface water that partially originates from the hyperacid
      crater lake of the Ijen volcano. Endemic dental fluorosis among local residents
      has been ascribed to F in water wells. In this study, the total F intake by
      children and adults was estimated, based on concentrations in well waters and
      foods throughout the area. These values were compared with the Lowest Observed
      Adverse Effect Level (LOAEL) for dental fluorosis among children and skeletal
      fluorosis among adults. Fluorosis hazard maps were prepared, identifying the most
      hazardous locations in the area. It was concluded that there is not only a high
      risk of dental fluorosis, but also of skeletal fluorosis. Based on the total
      daily intake, the lowest F concentration in drinking water that poses a risk of
      developing fluorosis is approximately 0.5 mg/l for dental fluorosis and 1.1 mg/l
      for skeletal fluorosis. This is below 1.5 mg/l, which is both the guideline value
      for drinking water from the World Health Organization (WHO) and the Indonesian
      drinking water standard. This is the first documented case of human health
      problems that may be directly associated with natural pollutants originating from
      a volcano-hosted crater lake.

PMID- 15993683
TI  - Lead bioaccumulation in earthworms, Lumbricus terrestris, from exposure to lead
      compounds of differing solubility.
AB  - This study examined the relative effects of soluble and less soluble Pb compounds
      on Pb accumulation by Lumbricus terrestris. The earthworms were exposed to
      composted cattle manure contaminated with a range of concentrations of either
      soluble lead acetate trihydrate (PbAc) (14.5, 72.2, 137, 257, and 603 microg/g)
      or less soluble lead carbonate (Pb(CO(3))(2)) (5.09, 171, 575, and 710 microg/g).
      Relative Pb bioaccumulation rates in earthworms from the PbAc and Pb(CO(3))(2)
      lead carbonate trials were compared over time (0, 20, 40, and 60 days). The two
      molecular forms of Pb were heavily adsorbed onto the organic matter. Relative
      soluble Pb concentrations in the manure pore water were very low, at 0.049% and
      0.022% of total Pb for PbAc and Pb(CO(3))(2), respectively. There was a
      significant uptake of lead by earthworms from both the readily soluble and less
      soluble forms of Pb. Regression surfaces relating organic matter total Pb
      concentration to exposure time and Pb body burden were compared. For the PbAc
      trial, the following equation was fitted: Body burden=2.3429+0.0014 x--0.0632
      y+0.0008 xy (R(2)=0.8494, p<0.0001). For the Pb(CO(3))(2) trial, the equation
      was: Body burden=-2.0760--0.0067 x-0.2297 y-0.0038 y(2)+0.0003 xy (R(2)=0.5686,
      p<0.0001) (for x=organic matter Pb concentration in microg/g and y=time in days).
      The Pb bioaccumulation resulting from the PbAc exposure was significantly higher
      than that from Pb(CO(3))(2). Body burdens of earthworms exposed to PbAc were
      linearly related to exposure time and total Pb concentration. Worms exposed to
      Pb(CO(3))(2) had non-linear Pb accumulation over time that suggested a decrease
      in Pb bioavailability with increasing exposure time. The results indicate that L.
      terrestris feeding on detritus in the upper soil levels can mobilize and
      accumulate Pb from the principal transformation products of metallic Pb, as at
      shooting ranges and lead smelter sites.

PMID- 15993684
TI  - Concentration of some toxic elements in Oryctolagus cuniculus and in its
      intestinal cestode Mosgovoyia ctenoides, in Dunas de Mira (Portugal).
AB  - The need for sentinel organisms reflecting small-scale changes in heavy metal
      pollution of different habitats has been previously stated and the role of
      terrestrial mammalian parasites has been pointed out as an important field of
      research aiming at the potential use of parasitic models as bioindicators. The
      scope of the present study was to assess the concentration of some toxic (Cd, Pb,
      As and Hg) elements in Dunas de Mira (Natura 2000 PTCON055) while testing the
      model constituted by the wild rabbit (Oryctolagus cuniculus Linnaeus, 1758) and
      its intestinal cestode parasite Mosgovoyia ctenoides Railliet, 1890 as potential
      bioindicators. Wild rabbits were harvested by hunters and analysed for intestinal
      cestodes. Samples of kidney, liver, intestinal mucosa, muscle of host and also M.
      ctenoides were taken and deep-frozen for posterior element analysis by ICP-MS. In
      general, levels of contamination in rabbit tissues were found to be low although
      some of the elements were detected in higher quantities when compared to other
      previous reports for wildlife in Europe. The highest quantity of Pb was found in
      rabbit muscle (3.81 ppm) while highest Cd and Hg values were found in kidney
      (1.02 and 0.08 ppm). Significant linear relationships were found between Pb
      concentration in the parasite and Pb concentration in kidney (P=0.0047), muscle
      (P=0.0002) and intestinal mucosa (P=0.0181) and between As concentration in the
      parasite and As concentration in liver (P=0.0024), kidney (P=0.0010), muscle
      (P=0.0003) and intestinal mucosa (P=0.0047). The most significant relationships
      for Pb and As were detected between element concentration in the cestode and in
      host muscle. However, maximum Pb and As concentrations in M. ctenoides were only
      twice as high as those found for rabbit kidney and therefore it is not possible
      to confirm the role of the model O. cuniculus/M. ctenoides as a promising
      bioindicator system unlike other mammalian host/cestode models tested in other
      studies. The contrasting results might be due to differences in the absorption
      processes in the tegument of different cestode families. Furthermore, the large
      size of the cestodes used in the present study might also explain the relatively
      low element concentration values obtained.

PMID- 15993685
TI  - Toxic and genotoxic evaluation of six antibiotics on non-target organisms.
AB  - The ecotoxicity of the following six antibiotics on aquatic organisms was
      investigated: Erythromycin, Oxytetracyclin, Sulfamethoxazole, Ofloxacin,
      Lincomycin and Clarithromycin. Bioassays were performed on bacteria, algae,
      rotifers, microcrustaceans and fish to assess acute and chronic toxicity, while
      SOS Chromotest and Ames test were used to detect the genotoxic potential of the
      investigated drugs. For risk assessment, the environmental impact was calculated
      by MEC/PNEC ratio using the available data from the literature regarding their
      occurrence in the aquatic environment and the toxicity data obtained from the
      bioassays performed. The ecotoxicological results showed that acute toxicity was
      in the order of mg/L while, for the chronic data the antibiotics were bioactive
      at concentrations in the order of microg/L, mainly for the algae. Drugs
      investigated were one or two order of magnitude less active against rotifers and
      crustaceans. Ofloxacin was the only genotoxic compound and Sulfamethoxazole,
      Ofloxacin and Lincomycin were mutagenic. As for environmental risk, the
      macrolides were found to be the most harmful for the aquatic environment.

PMID- 15993686
TI  - Use of the aquatic protozoa to formulate a community biotic index for an urban
      water system.
AB  - Protozoan were collected from 16 stations in water system of Changde City (China)
      using the PFU method. Sampling programs were conduced on a yearly basis, with
      seasonal frequency at diverse sites in the water system and 488 species of
      protozoa was identified. At the same time, Water sampling from these stations was
      conducted and various water chemical parameters, including DO, COD, BOD(5),
      NH(3), TP, and Volatile Phenol, were analyzed. The aim of the research was, on
      one hand, using chemical method to take an investigation to the water pollution
      status of Changde City; on the other hand, using protozoan to make an evaluation
      to the water quality. With the chemical water parameters and protozoa data, a
      biotic index was derived for the investigated region. The species pollution value
      (SPV) of 469 protozoa species was established, and the community pollution value
      (CPV) calculated from SPV was used to evaluate water quality. The method of the
      biotic index was tested and the result showed that CPV calculated from SPV had a
      close correlation with the degree of water pollution (p<0.00001). This indicated
      that the method of the biotic index is reliable. The water quality degrees
      divided by CPV were suggested.

PMID- 15993687
TI  - Nitrate contamination in private wells in rural Alabama, United States.
AB  - Nitrate-N (NO(3)(-)-N) concentrations in random water samples from rural
      residential wells in Alabama, USA, were analyzed over an 8-year period from 1992
      to 1999. Data collected included land use, well depth, septic tank use and
      distance from the well and also livestock and cropping activities around wells.
      Of 1021 available data sets, 36% of samples showed nitrate-N concentration of
      higher than 1.0 mg/l, indicating the possible influence of anthropogenic
      activities. About 1.7% of samples had a nitrate-N concentration of higher than 10
      mg/l. Results indicate nitrate contamination in groundwater was relatively low
      and stable in Alabama. Logistic regression analysis indicated that well depth,
      pH, and cropping activity were factors of statistical significance in influencing
      nitrate-N concentration in these wells. Factors such as septic tank use and
      livestock activities did not show a close link to nitrate-N concentration in
      wells tested.

PMID- 15993688
TI  - Isotopic characterisation of the historical lead deposition record at Glensaugh,
      an organic-rich, upland catchment in rural N.E. Scotland.
AB  - As part of a wider investigation of the biogeochemistry and fate of Pb deposited
      from the atmosphere at Glensaugh, a rural upland catchment in N.E. Scotland, the
      concentration and isotopic composition of Pb were determined in four thinly
      sectioned monolith cores (25 cm) of peat collected at altitudes of 426--434 m
      from different faces of Thorter Hill and in a series of 21 10-cm unsectioned
      cores of peat and organic-rich soil along a transect from near the top (434 m) to
      the bottom (224 m) of the catchment. Depth profiles of Pb concentration and
      (206)Pb/(207)Pb ratio were similar for the longer cores. Subsurface Pb maxima
      (238--489 mg kg(-1)) typically occurred below (206)Pb/(207)Pb minima (1.123
      1.134). One core was (210)Pb-dated and had a fairly constant (206)Pb/(207)Pb
      value of 1.170 from mid-19th century to ca. 1930, followed by a decline
      (attributable to the increasing influence of Australian Pb of much lower
      (206)Pb/(207)Pb ratio) to 1.134 by the early 1990s, and then a rapid increase to
      1.160 by 2002, after the phased withdrawal of leaded petrol. The fluxes of Pb
      increased from 15 mg m(-2) year(-1) in the late 19th century to a peak of 60 mg
      m(-2) year(-1) ca. 1960, before declining steadily to 3.6 mg m(-2) year(-1) by
      the beginning of the 21st century. Some 40% of the anthropogenic Pb in the core
      had been deposited prior to 1900. The mean anthropogenic Pb inventory of the four
      longer cores was 7.4+/-1.5 g m(-2), of which approximately 70% occurred in the
      top 10 cm, in good agreement with the inventories of the shorter cores collected
      above 400 m. These inventories are higher than those of the industrial central
      belt of Scotland, probably because of enhanced deposition at altitude. This is
      consistent with the derived average (210)Pb flux of 198+/-11 Bq m(-2) year(-1),
      which is twice that of typical UK (210)Pb deposition and the rainfall for the
      site. The past deposition of Pb at Glensaugh, including that from sources (e.g.,
      smelting, coal combustion) other than leaded petrol, has clearly been
      considerable. Even since the introduction of leaded petrol ca. 1930, car-exhaust
      emissions may have accounted for no more than 35% of the Pb deposited.

PMID- 15993689
TI  - Lead isotopes in soils near five historic American lead smelters and refineries.
AB  - This survey of soil lead in the vicinity of old industrial sites examines how the
      stable isotope patterns vary among the sites according to the sources of the lead
      ore processed at each site. Lead smelters and refineries, which closed down
      decades ago, are the basis of this investigation. Samples were taken from near
      five old factory sites in Collinsville and Alton (Illinois), Ponderay (Idaho),
      East Chicago (Indiana) and Omaha (Nebraska). Historical records were searched for
      accounts of the sources of the lead. Lead concentrations were measured by atomic
      absorption flame spectrophotometry, and stable isotopic analysis was done by
      plasma ionization mass spectrometry. At every site visited, remnants of the old
      factories, in terms of soil lead pollution, could be found. In spite of potential
      complications of varying smelter feedstock sourced from mines of different
      geological age, it was possible to match the isotopic patterns in the soils with
      the documented sources of the ores. The Collinsville and Alton sites resembled
      Missouri lead. The Ponderay value was higher than major Bunker Hill, Idaho
      deposits, but closer to the minor, nearby Oreille County, Washington ores. Mostly
      Utah ore was used in East Chicago. The Omaha soil reflects lead from Mexico,
      Colorado and Montana.

PMID- 15993690
TI  - Historical CO(2) emission and concentrations due to land use change of croplands
      and pastures by country.
AB  - This work is aimed at estimating the historical land use change emission and
      concentrations of CO(2) by country. Calculating the area differences of each
      biome (associated to carbon factors) converted to cropland (including urban
      areas) and pastures by country we calculated the land use change CO(2) emission
      over the past 300 years using a new dataset, which is a well known one in the
      literature: the HYDE land use database. According to IPCC-SR-LULUCF (2000) the
      net cumulative global CO(2) emission from land use change (1850--1990) is
      estimated to have been 499+/-205 Tg CO(2), our result is 360 Tg CO(2) for the
      same period, and Houghton's (Houghton, RA, 2003a. Revised estimates of the annual
      net flux of carbon to the atmosphere from changes in land use and land management
      1850--2000. Tellus 55B, 378--390) result is 492 Tg CO(2). We have also used the
      Bern model (IPCC-TAR-WG1, 2001) of decay time of CO(2) to estimate the
      concentrations of CO(2) in the year 1990 due to land use change emission, once
      the CO(2) emission from the past is still decaying in the atmosphere.

PMID- 15993691
TI  - Regional differences in collagen stable isotope and tissue trace element profiles
      in populations of long-tailed duck breeding in the Canadian Arctic.
AB  - Adult long-tailed ducks (Clangula hyemalis) were collected from nine locations
      across their breeding grounds in northern Canada and measurements of stable
      isotopes of carbon (delta(13)C), nitrogen (delta(15)N) and sulfur (delta(34)S) in
      bone collagen were used to investigate if relative use of freshwater habitats
      such as the Great Lakes (with expected depleted stable isotope profiles) compared
      with coastal marine environments (with expected enriched stable isotope foodweb
      profiles) could explain tissue trace element profiles. Contrary to expectation,
      all three stable isotopes did not covary in our sample, suggesting that
      mechanisms other than simple freshwater vs. marine isotopic gradients were
      involved among populations. All three stable isotopes varied significantly with
      collection location and both delta(15)N and delta(13)C values varied
      significantly between sexes suggesting that males exploit either a different food
      base or occur in different geographic areas than females for at least part of the
      year. The delta(34)S data, in particular, suggested that many of the birds
      breeding in the western Canadian Arctic probably overwinter in the Great Lakes
      along with many of the birds breeding in Hudson Bay. Males at the majority of
      collection locations had higher concentrations of hepatic Hg (1.1-8 microg/g dw),
      Cu (25-40 mug/g dw), Se (7.3-27 mug/g dw) and renal Cd (33-129 microg/g dw) than
      females. Concentrations of Hg, Cu and Cd were well below toxicological threshold
      levels found in the literature. However, hepatic Se concentrations in 64% of the
      females exceeded 10 mug/g dw and concentrations in 8% of the birds measured
      exceeded 33 microg/g dw suggesting levels of potential concern.

PMID- 15993692
TI  - Mercury concentrations in water from an unconfined aquifer system, New Jersey
      coastal plain.
AB  - Concentrations of total mercury (Hg) from 2 microg/L (the USEPA maximum
      contaminant level) to 72 microg/L in water from about 600 domestic wells in
      residential parts of eight counties in southern New Jersey have been reported by
      State and county agencies. The wells draw water from the areally extensive (7770
      km(2)) unconfined Kirkwood-Cohansey aquifer system, in which background
      concentrations of Hg are about 0.01 microg/L or less. Hg is present in most
      aquifer materials at concentrations <50 microg/kg, but is at 100--150 microg/kg
      in undisturbed surficial soils. No point sources of contamination to the affected
      areas have been conclusively identified. To determine whether high levels of Hg
      in ground water are related to a particular land use and (or) water chemistry,
      water samples from 105 wells that tap the aquifer system were collected by the
      United States Geological Survey. These included randomly selected domestic wells,
      domestic and observation wells in selected land uses, and sets of clustered
      observation wells--including two sets that are downgradient from residential
      areas with Hg-contaminated ground water. Hg concentrations in filtered samples
      (Hg(f)) were at or near background levels in water from most wells, but ranged
      from 0.1 to 3.8 microg/L in water from nearly 20% of wells. Hg(f) concentrations
      from 0.0001 to 0.1 microg/L correlated significantly and positively with
      concentrations of other constituents associated with anthropogenic inputs (Ca,
      Cl, Na, and NO(3)) and with dissolved organic carbon. Hg(f) concentrations >0.1
      microg/L did not correlate significantly with concentrations of the inorganic
      constituents. Hg(f) concentrations near or exceeding 2 microg/L were found only
      in water from wells in areas with residential land use, but concentrations were
      at background levels in most water samples from undeveloped land. The spatial
      distribution of Hg-contaminated ground water appears to be locally and regionally
      heterogeneous; no extensive plumes of Hg contamination have yet been identified.

PMID- 15993693
TI  - Estimation of biogenic volatile organic compounds emissions in subtropical island
      -Taiwan.
AB  - Elevated tropospheric ozone is harmful to human health and plants. It is formed
      through the photochemical reactions involving volatile organic compounds (VOCs)
      and nitrogen oxides (NO(x)). The elevated ozone episodes occur mainly in summer
      months in the United States, while the high-ozone episodes frequently occur
      during the fall in Taiwan. The unique landscape of Taiwan produces tremendous
      amounts of biogenic VOCs in the mountain regions that are adjacent to
      concentrated urban areas. The urban areas, in turn, generate prodigious amounts
      of anthropogenic emissions. Biogenic VOC emissions have direct influence on
      tropospheric ozone formation. To explore the air quality problems in Taiwan, this
      study attempts to develop a biogenic VOC emission model suitable for air quality
      applications in Taiwan. The emission model is based on the Biogenic Emissions
      Inventory System Version 2 and coupled with a detailed Taiwan land use database.
      The 1999 total Taiwan biogenic VOC emissions were estimated at 214,000 metric
      tons. The emissions of isoprene, monoterpenes, and other VOCs were about 37.2%,
      30.4%, and 32.4% of total biogenic VOC emissions, respectively. The annual total
      biogenic VOC emission per unit area was more than two times the value of that in
      any European country, implying that detailed emissions estimates in any size of
      region will benefit the global biogenic emission inventories.

PMID- 15993694
TI  - Distribution and mobility of mercury in soils from an old mining area in Mieres,
      Asturias (Spain).
AB  - Mercury content in soils near abandoned mine wastes in the mercury mining area of
      Mieres (Asturias, Spain) is highly elevated as a result of the long period of
      mining and abundant Hg production. In this work, an evaluation of Hg
      concentration, distribution, and mobility in three soil samples from the
      immediate vicinity of a chimney used for vapour evacuation during
      pyrometallurgical treatment of the ore was carried out. For that purpose, total
      Hg contents were determined for the original samples and their grain-size
      subsamples. The study of mercury mobility in the original samples and in the
      different particle-size subsamples was made by the application of a sequential
      extraction method. Results showed that Hg concentration in soils decreases
      directly with the distance from the chimney and the dispersion of Hg is not
      influenced by the topographic height of the site tested. The sample collected in
      the base of the chimney exhibited appreciable amounts of mobile Hg. In general, a
      higher Hg concentration was found for the finest particle-size subsamples. Hg
      mobility was found to be higher for quite developed soils. The sample collected
      downstream from the chimney showed a significant Hg mobile content as a result of
      a more intensive weathering. An increase of Hg mobility at decreasing particle
      size was found in all three analysed samples.

PMID- 15993695
TI  - Antibiotic resistance and antibacterial activity in heterotrophic bacteria of
      mineral water origin.
AB  - Antibiotic resistance and antibacterial activity were determined on heterotrophic
      bacteria isolated from mineral waters. Of the 120 isolates Pseudomonas spp.
      (55.8%) was the predominant group followed by Acinetobacter spp. (14.17%),
      Flavobacterium spp. (10.83%), Achromobacter spp. (10%), Burkholderia cepacia
      (3.3%), Agrobacterium/radiobacter (2.5%), Moraxella spp. (1.7%), Aeromonas
      hydrophila (1.7%). Over 80% of the isolates were resistant to one or more
      antibiotics and the highest resistance was found for chloramphenicol, ampicillin,
      colistin and sulfamethizole (60%, 55%, 50% and 47.5%, respectively). Strains with
      multiple antibiotic resistance (MAR) represented 55% of isolates and the most
      resistant organism belonged to the genus Pseudomonas. Of 40 randomly selected
      strains, 27 (67.5%) had antibacterial activity towards one or more indicators.
      This activity, found in a high percentage in the genus Pseudomonas (92%), emerged
      mainly against closely related microorganisms. Several producers were active also
      against Escherichia coli, Salmonella, Listeria monocytogenes and Staphylococcus
      aureus. Forty-six percent of the isolates harboured 1 to 5 plasmids with
      molecular weights ranging from 2.1 to 41.5 MDa.

PMID- 15993696
TI  - Influence of algal and bacterial particulate organic matter on benzo[a]pyrene
      bioaccumulation in Daphnia magna.
AB  - In order to better asses the influence of organic matter on the bioavailability
      of hydrophobic organic contaminants, the effect of algae and POM of bacterial
      origin on the bioaccumulation of benzo[a]pyrene in Daphnia magna was evaluated.
      The bioaccumulation was monitored with increasing concentrations of particulate
      organic matter (POM) and dissolved organic matter (DOM). In all experiments, the
      presence of POM greatly reduced the bioaccumulation of benzo[a]pyrene. The
      reduction was more pronounced in the presence of algae, for which we observed a
      99%-reduction effect in the presence of 6 x10 (5) cell/mL (equivalent to 5.3 mg
      C/L). The bioaccumulation of benzo[a]pyrene was decreased by 49% by organic
      matter of bacterial origin at 4.7 mg C/L. Assuming that benzo[a]pyrene was
      partitioned between water, DOM and POM and supposing that D. magna accumulated
      free benzo[a]pyrene via respiration and POM-bond benzo[a]pyrene via ingestion,
      bioaccumulation data allowed to estimate the dietary uptake rate of
      benzo[a]pyrene as well as partitioning coefficients K(POC) and K(DOC). Despite
      the ingestion of contaminated particles, we could not observe any dietary uptake
      of benzo[a]pyrene in daphnids. We verified, as usually supposed, that the
      bioaccumulation of benzo[a]pyrene to D. magna occurs mainly via direct contact.
      Very high partitioning coefficients (log K(POC) between 5.2 and 6.2) were
      estimated. This study pointed out the great influence of biogenic organic matter
      on the fate and the bioavailability of benzo[a]pyrene in aquatic ecosystems.

PMID- 15993697
TI  - Analytical electron microscopy of combustion particles: a comparison of vehicle
      exhaust and residential wood smoke.
AB  - Particulate matter has been associated with a number of adverse health effects.
      Since combustion particles from vehicle exhaust and wood smoke are common
      constituents of ambient air, the morphology and elemental composition of
      particles from these two sources were analysed and compared using single particle
      analysis. Ambient air particles were collected in locations dominated by vehicle
      exhaust or residential wood smoke. To verify the source contributions to the
      ambient air samples, particles were collected directly from the combustion
      sources. All particulate samples were analysed on carbon extraction replica by
      transmission electron microscopy (TEM) and X-ray microanalysis (XRMA). The
      particles were classified into four groups based on morphology and elemental
      composition. Carbon aggregates were the only particles identified to originate
      from combustion sources and accounted for more than 88% of the particle numbers
      in the ambient air samples from both sources. The carbon aggregates were
      therefore further analysed with respect to morphology and elemental composition
      on germanium extraction replica. Carbon aggregates from vehicle exhaust were
      characterised by higher levels of Si and Ca compared to wood smoke aggregates
      that contained higher levels of K. The S content in aggregates from both sources
      was probably caused by interaction with gases in the air. Furthermore, the
      diameters of primary particles from vehicle exhaust were significantly smaller
      (27+/-7 nm) than the diameters for wood smoke (38+/-11 nm). The observed
      differences in elemental profiles and primary particle diameters for vehicle
      exhaust and wood smoke may influence the health effects caused by these
      particles.

PMID- 15993698
TI  - An overview on bioaerosols viewed by scanning electron microscopy.
AB  - Bioaerosols suspended in ambient air were collected with single-stage impactors
      at a semiurban site in southern Germany during late summer and early autumn.
      Sampling was mostly carried out at a nozzle velocity of 35 m/s, corresponding to
      a minimum aerodynamic diameter (cut-off diameter) of aerosol particles of 0.8
      mum. The collected particles, sampled for short periods ( approximately 15 min)
      to avoid pile-up, were characterized by scanning electron microscopy (SEM). The
      observed bioaerosols include brochosomes, fungal spores, hyphae, insect scales,
      hairs of plants and, less commonly, bacteria and epicuticular wax. Brochosomes,
      which serve as a highly water repellent body coating of leafhoppers, are hollow
      spheroids with diameters around 400 nm, resembling C(60) or footballs (soccer
      balls). They are usually airborne not as individuals but in the form of large
      clusters containing up to 10,000 individual species or even more. Various types
      of spores and scales were observed, but assignment turned out be difficult due to
      the large number of fungi and insects from which they may have originated.
      Pollens were observed only once. The absence these presumably elastic particles
      suggests that they are frequently lost, at the comparatively high velocities, due
      to bounce-off from the nonadhesive impaction surfaces.

PMID- 15993699
TI  - Certain antioxidant enzymes of Allium cepa as biomarkers for the detection of
      toxic heavy metals in wastewater.
AB  - The utility of antioxidant enzymes, viz glutathione-S-transferase (GST),
      glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), ascorbate
      peroxidase (APX), glutathione peroxidase (GPX), monodehydroascorbate reductase
      (MDHAR) and dehydroascorbate reductase (DHAR), as biomarkers of heavy metal
      pollution in water was investigated using the Allium cepa (onion) system. These
      antioxidant enzymes were assayed in onion bulbs exposed to certain heavy metals
      taken separately, the test metals taken in combination as well as the industrial
      wastewater especially found to contain these metals. GST exhibited significantly
      enhanced activity upon treatment with individual heavy metals. However, GR, SOD
      and CAT did not show such a pronounced increase in activities. At higher heavy
      metal concentrations, GR, SOD and CAT showed a steep decline while GST activity
      still showed a rise. Moreover, APX, GPX and MDHAR also exhibited remarkable
      induction with increase in the concentration of individual heavy metals. However,
      there was no significant change in DHAR activity with respect to the controls.
      Metabolites like ascorbate (ASC) and glutathione (GSH) exhibited significant
      decline with increase in the concentration of individual heavy metals while the
      level of H(2)O(2) continued to display the rise up to a heavy metal concentration
      of 100 microM, after which it showed a gradual decline. A. cepa bulbs treated
      with wastewater sample showed enzyme activity profiles similar to that shown with
      heavy metals, thereby suggesting the presence of heavy metals in the test
      wastewater. Atomic absorption spectrophotometry also detected large amounts of
      Cd, Cr, Cu, Hg, Pb and Zn in the test water sample. The metal mixture, containing
      the amounts of heavy metals equivalent to those found in the wastewater, resulted
      in steep declines in GR, SOD and CAT activities in A. cepa while GST showed a
      rise. However, when this metal mixture was diluted to 2000-fold, GR, SOD and CAT
      also showed enhanced activities compared with the controls. Contrary to the above
      finding, APX, GPX and MDHAR exhibited the rise in activities in A. cepa exposed
      to the metal mixture at all dilutions. In the presence of cycloheximide, all the
      enzymes returned to the levels of untreated controls while chloramphenicol did
      not have any effect on the test enzymes, thereby suggesting de novo protein
      synthesis of the test antioxidant enzymes in the cytosolic compartment of the
      cell as a result of exposure to the heavy metals.

PMID- 15993700
TI  - Removal of selenium from river water by a microbial community enhanced with
      Enterobacter taylorae in organic carbon coated sand columns.
AB  - Discovering an effective means to remove selenium (Se) from Se-contaminated water
      is fundamental in minimizing environmental contamination and ensuring wildlife
      protection. In this study, Enterobacter taylorae attached to tryptic soy agar
      (TSA) coatings was used in sand columns to remove Se from a natural river water.
      During 80 days of the experiment, E. taylorae and indigenous Se(VI) reducers in
      the water used organic carbon coatings to effectively reduce Se(VI) to Se(0).
      About 95% and 70% of the influent Se (469 microg/L) was reduced to Se(0),
      respectively, in the columns with and without E. taylorae and 94--98% of the
      newly formed Se(0) was trapped in the columns. Analysis of Se species in effluent
      at the end of the experiment revealed that organic Se from the columns with E.
      taylorae was similar to that in influent (0.567 microg/L). This study indicates
      that using organic coatings attached with Se(VI) reducers in a biotreatment
      system may be a potentially feasible method to remove Se from Se-contaminated
      water in field.

PMID- 15993701
TI  - Fetal cells and cell free fetal nucleic acids in maternal blood: new tools to
      study abnormal placentation?
AB  - The analysis of fetal cells, and more recently cell free fetal nucleic acids, in
      maternal blood has to date largely been concerned with the development of risk
      free methods for prenatal diagnosis. Although elevated feto-maternal cell
      trafficking has long been associated with preeclampsia, it has only recently been
      shown that this perturbation is an early event in these pregnancies, occurring
      well in advance of the onset of symptoms. In a separate development, analogous
      observations have been made concerning the levels of circulatory fetal nucleic
      acids in maternal plasma. Subsequent studies have shown that changes in these two
      parameters may also occur in other pregnancy related disorders including preterm
      labour, intra-uterine growth retardation, hyperemesis gravidarum or even
      pregnancies at high altitude. A striking finding of these examinations was that
      preterm labour was associated with an elevated release of cell free fetal nucleic
      acids but not with an increment in feto-maternal cell trafficking. This suggested
      that the analysis of the mechanisms regulating trans-placental cell trafficking
      or liberation of circulatory fetal nucleic acids may provide key insights into
      the fundamentally different placental lesions underlying these disorders. As
      such, circulatory fetal cells and nucleic acids may be viewed as new tools to
      study alterations in placentation.

PMID- 15993702
TI  - Tissue-specific and ubiquitous basic helix-loop-helix transcription factors in
      human placental trophoblasts.
AB  - Tissue-specific class B basic helix-loop-helix (bHLH) transcription factors,
      dimerising with ubiquitously produced class A bHLH proteins, play a major role in
      murine trophoblast development. Here, we investigated expression patterns of
      class A and B bHLH factors in the human placenta and different trophoblast
      culture systems. Semi-quantitative RT-PCR and RNase protection assay revealed
      expression of the tissue-restricted factors Hash-2, I-mfa and Stra13 in placentae
      of early and late pregnancy, in purified villous trophoblasts as well as in
      invasive trophoblasts isolated from first trimester villous explant cultures.
      Accordingly, RNA in situ hybridisation localised Hash-2, I-mfa and Stra13 to the
      trophoblast epithelium, cell columns and extravillous trophoblasts invading
      maternal decidua. Villous stromal cells in situ and cultivated placental
      fibroblasts also produced I-mfa and Stra13 but failed to express Hash-2. The
      widely expressed class A proteins, E12/E47 were absent from all placental cell
      types while ITF-2 was restricted to placental stromal cells of early and late
      gestation. In contrast, HEB was identified in all trophoblast cell types using RT
      PCR, Western blotting and immunohistochemistry. The negative HLH-regulators Id-1
      and Id-2 lacking the DNA-binding domain, were detected in villous stromal cells
      and different cytotrophoblast subtypes but were absent from the syncytium. The
      data suggest that a complex interplay of activators (Hash-2, HEB) and repressors
      (Stra13, I-mfa) could be involved in extravillous trophoblast differentiation
      whereas downregulation of Id proteins could play a role in syncytialisation.

PMID- 15993703
TI  - Toll-like receptors and their role in the trophoblast.
AB  - The aim of this review is to discuss the role of Toll-like receptors at the
      maternal-fetal interface and the capacity of trophoblast cells to initiate innate
      immune responses towards infection. The maternal-fetal interface represents an
      immunologically unique site that must promote tolerance to the allogenic fetus,
      whilst maintaining host defense against a diverse array of possible pathogens.
      Clinical studies have shown a strong association between certain complications of
      pregnancy and intrauterine infections. Therefore, innate immune responses against
      microorganisms at the maternal-fetal interface may have a significant impact on
      the success of a pregnancy. There is growing evidence that trophoblast cells are
      able to recognize and respond to pathogens through the expression of Toll-like
      receptors, an important part of innate immunity. This review will discuss the
      role of Toll-like receptors at the maternal-fetal interface, the potential for
      trophoblast cells to function as components of the innate immune system and the
      impact TLR-mediated trophoblast responses may have on pregnancy outcome.

PMID- 15993704
TI  - Multiple anti-apoptotic pathways stimulated by EGF in cytotrophoblasts.
AB  - Epidermal growth factor (EGF) reduces apoptosis in primary cytotrophoblast (CT)
      in culture through two separate pathways: the extracellular signal related kinase
      (ERK) 1/2 and phosphatidyl inositol 3-kinase (PI-3 kinase) paths. Whether other
      pathways are involved in survival signalling is unknown. We here show that the c
      Jun NH2 terminal kinase (JNK) and the mitogen activated kinase (MAPK) p38 are
      also activated by EGF as seen by increases in JNK and p38 phosphorylation.
      However, inhibition of JNK phosphorylation with the specific inhibitor SP600125
      increases apoptosis in a manner refractory to the addition of EGF but inhibition
      of p38 phosphorylation with its specific inhibitor SB 203580 does not increase
      apoptosis. EGF also activates sphingosine kinase-1 (SPHK-1), which converts
      sphingosine to sphingosine-1-phosphate, and its inhibition with dimethyl
      sphingosine (DMS) increased trophoblast death. Inhibition of SPHK-1 also did not
      affect EGF stimulated phosphorylation of PI-3 kinase, Akt, ERK1/2 or p38 but
      inhibition of PI-3 kinase with a specific inhibitor LY294002 partly (40%)
      inhibited the EGF-stimulated increase in SPHK-1 activity. We conclude that, in
      addition to the PI-3 kinase and ERK1/2 pathways, EGF acts through its receptor to
      stimulate JNK, p38 and SPHK-1 pathways, but that the JNK and SPHK-1, and not the
      p38, pathways are involved in suppressing apoptosis. This information provides
      evidence that EGF stimulates survival along multiple pathways that differ in
      trophoblast and other cell types.

PMID- 15993705
TI  - Expression of HERV-W Env glycoprotein (syncytin) in the extravillous trophoblast
      of first trimester human placenta.
AB  - Although the extravillous trophoblastic invasion has a critical role in human
      placental development, nothing is known about HERV-W expression in the
      extravillous phenotype. The aim of the present study was to localize in first
      trimester placenta the expression of HERV-W Env glycoprotein and its receptor all
      along the differentiation pathway of the extravillous phenotype. In addition
      using an in vitro model of extravillous cytotrophoblastic cell isolation and
      invasion we investigated the presence of HERV-W transcripts and envelope
      glycoprotein in cultured extravillous trophoblastic cells. Using monoclonal and
      polyclonal antibodies, the glycoprotein was immunolocalized in all the cell types
      of the extravillous phenotype lineage: cytotrophoblastic cells of the column,
      interstitial extravillous trophoblastic cells, multinucleated giant cells and
      endovascular trophoblast. Furthermore, using a polyclonal antibody, the D
      mammalian virus receptor was also localized in the various extravillous
      trophoblastic phenotypes. In addition, the presence of HERV-W transcripts and
      protein was demonstrated in cultured extravillous trophoblastic cells. HERV-W Env
      glycoprotein expressed in villous and extravillous trophoblast can be considered
      as a specific marker of the human trophoblast.

PMID- 15993707
TI  - Endovascular trophoblast invasion and associated structural changes in uterine
      spiral arteries of the pregnant rat.
AB  - The involvement of endovascular trophoblast in fibrinoid deposition, replacement
      of the endothelium and vascular smooth muscle breakdown is studied in spiral
      arteries of the mesometrial triangle from day 15 to day 21 of rat pregnancy, by
      examining arterial cross sections after staining for cytokeratin, PAS, CD31 and
      alpha-actin. From day 15 to day 18 of pregnancy, fibrinoid deposition underneath
      the endovascular trophoblast increases gradually, whereas the amount of
      endovascular trophoblast in invaded arteries remains constant. CD31 staining is
      significantly reduced in sub-ET (= underlying the endovascular trophoblast) as
      compared to extra-ET (= outside the endovascular trophoblast) and no-ET (= non
      invaded arterial sections) at each time-point of pregnancy examined (P < 0.005
      and P < 0.0005 at each day of pregnancy), whereas alpha-actin staining is reduced
      both in sub-ET and in extra-ET as compared to no-ET. During pregnancy, CD31
      staining in sub-ET initially declines, but increases significantly on day 21 (P <
      0.001 versus d20) suggesting re-endothelialization of the vascular wall. In
      conclusion, changes in spiral arteries of pregnant rats reveal striking
      similarities with physiological changes seen in human pregnancy, thus emphasizing
      the usefulness of this species as an experimental model for studying normal and
      complicated pregnancies in humans.

PMID- 15993708
TI  - Ultrastructural aspects of long-term cat placental explant culture.
AB  - Changes in tissue architecture and ultrastructure in the cat placenta during long
      term explant culture have been examined over an 11-day period. Pieces of cat
      placenta, dissected from the lamellar region, were cultured in CMRL-1066 medium
      and tissue was fixed for electron microscopy at 2, 5, 7, and 11 days' culture, as
      well as before culture was initiated (day 0). Four samples were examined at each
      time point. After two days, the trophoblast basal lamina and attached
      cytotrophoblast cells had begun to separate from the syncytium and the
      cytotrophoblasts were spreading over the surface of the exposed fetal stromal
      compartment, and by five days were showing signs of growth. At seven days'
      culture, cytotrophoblast multilayering was common, and vascular and stromal
      components were also well preserved with collagen biosynthesis evident. By 11
      days, the centre of the culture was compacted and degenerate with loss of tissue
      architecture, but on the outside polyp-like growths could be seen, with a well
      developed covering of trophoblast containing fat and secretory droplets, lining a
      connective tissue matrix and stromal components. The cat placenta, therefore,
      like the human, has the capacity for regrowth in explant culture, including both
      trophoblast and stromal components.

PMID- 15993706
TI  - Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt
      1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in
      normotensive and preeclamptic pregnant women.
AB  - The soluble VEGF receptor, sFlt-1 (otherwise referred to as sVEGFR-1), has been
      implicated in the pathogenesis of preeclampsia. The preeclamptic placenta has
      been previously demonstrated to produce high levels of the soluble VEGF receptor.
      Here we tested the hypothesis that peripheral blood mononuclear cells (PBMCs) may
      also represent an additional source for circulating sFlt-1 during normal and
      preeclamptic pregnancies. We first demonstrate that preeclamptic placentae show
      five-fold increased Flt-1 and sFlt-1 mRNA levels. We also show that the Flt-1 and
      sFlt-1 levels are eight-fold higher in preeclamptic placentae if we collect
      biopsies without rinsing them in saline to remove excess blood. Cultured villous
      explants from women with preeclampsia failed to show the increased amount of Flt
      1 and sFlt-1 mRNA that was observed in the placental biopsies of normal pregnancy
      and preeclampsia. Under normoxic conditions the Flt-1 and sFlt-1 mRNA levels in
      the explants were 3.11+/-0.6 fold in normal pregnancy and 3.6+/-0.4 fold in women
      with preeclampsia (p = NS by ANOVA). However, the same villous explants showed
      hypoxic induction of Flt-1 mRNA (NP 3.96+/-0.4 fold, p = NS and PE 5.24+/-0.6
      fold, p < 0.05 by ANOVA). We analyzed Flt-1 and sFlt-1 protein levels in the
      peripheral blood mononuclear cells (PBMCs) to analyze the possibility of an extra
      placental sFlt-1 source. Our results indicate that PBMCs of pregnant women are
      capable of expressing variable amounts of Flt-1 proteins. PBMCs from pregnant
      women exposed to hypoxia show up-regulation of HIF-1alpha and Flt-1 proteins.
      PBMCs obtained from women with preeclampsia (n = 9) produced significantly higher
      amounts of sFlt-1 under normal tissue culture conditions (104.6+/-14.3 pg/ml vs.
      46.23+/-5.03 pg/ml, p < 0.05 by ANOVA) and much higher concentrations under
      hypoxia (196.74+/-26.3pg/ml vs. 83.3+/-13.6pg/ml, p < 0.05 by ANOVA) than PBMCs
      from normal pregnant women (n = 11). Moreover, analysis of PBMCs from a different
      group of women with a history of preeclampsia showed persistent abnormality of
      Flt-1 women one year post-partum. The present study indicates that Flt-1
      dysregulation in PBMCs of pregnant women resulting in over-expression of sFlt-1
      could be an additional (extra-placental) source of sFlt-1 that contributes to the
      pathogenesis of preeclampsia.

PMID- 15993709
TI  - Campath-1H does not alter bone marrow cell regulatory function.
AB  - We have previously reported in laboratory volunteers (in vitro) and renal
      transplant recipients (ex vivo) that bone marrow cells (BMC) are potent
      downregulators of the immune response. Also, the use of alemtuzumab (Campath-1H,
      C1H) for immunodepletion is associated with the most potent lasting effects yet
      seen on T-cell immunity in renal transplantation. We questioned whether the
      administration of C1H to kidney allograft recipients of donor bone marrow cell
      (DBMC) infusions would lead to stronger or weaker immunoregulatory effects. Human
      BMC depleted of T cells (nT-BMC) were either untreated or treated with C1H and
      rabbit complement and compared for their ability to downregulate autologous or
      allogeneic T-cell responses and to generate T regulatory (T reg) cells. The
      proliferative responses to anti-CD3 monoclonal antibody of T cells derived from
      cocultures with C1H-treated or untreated autologous nT-BMC were equally
      suppressed, i.e., an equivalent alteration in CD3 complex signaling, not regained
      by the addition of interleukin 2. Adenosine triphosphate levels were also
      markedly reduced in T cells both from C1H-treated and untreated nT-BMC
      cocultures. The ability of C1H-treated or untreated nT-BMC to suppress autologous
      T-cell cytotoxic function was also equivalent, with a marked, but equivalent,
      capacity to induce CD4/CD25(high) T regs from CD3(+) cells, which effectively
      downregulated cytotoxic T cells. To mimic the clinical infusion of DBMC into
      (allogeneic) recipients, peripheral blood mononuclear cells were also cultured
      with allogeneic C1H-treated and untreated nT-BMC. T cells derived from these
      cultures secondarily stimulated with the same-donor mature antigen-presenting
      cells exhibited suppressed cytotoxicity by 85% and 54%, respectively. These in
      vitro studies suggest that C1H does not abrogate BMC immunoregulation and thus
      may allow its lympho-depleting effect to be synergistic.

PMID- 15993710
TI  - Large-scale preparation of human anti-third-party veto cytotoxic T lymphocytes
      depleted of graft-versus-host reactivity: a new source for graft facilitating
      cells in bone marrow transplantation.
AB  - Induction of donor type chimerism in mildly prepared hosts without graft-versus
      host disease (GvHD) is a most desirable goal in bone morrow transplantation. We
      have recently demonstrated in a mouse model that donor veto cytotoxic T
      lymphocytes (CTLs) can facilitate the induction of donor type chimerism in
      sublethally irradiated recipients without causing GvHD if they are effectively
      depleted of alloreactivity against host cells by means of stimulation against a
      third party. We extend this approach to human cells, by preparing CTLs in two
      major steps: primary culture in the absence of interleukin 2, leading to death by
      neglect of antihost clones, and addition of interleukin 2 and subsequent dilution
      of antihost clones as a consequence of the expansion of the anti-third-party
      clones. CTLs prepared in this way specifically suppress host cytotoxic T cells
      directed against antigens of the donor, but not against fourth-party antigens, as
      demonstrated in a standard (51)Cr release assay. We conclude that human anti
      third-party CTLs afford a new source of veto cells that are depleted of potential
      graft-versus-host-reactive clones. The cells generated by this approach could
      potentially be used to facilitate engraftment of allogeneic hematopoietic stem
      cells.

PMID- 15993711
TI  - Statins affect cell-surface expression of major histocompatibility complex class
      II molecules by disrupting cholesterol-containing microdomains.
AB  - Statins, the main therapy for hypercholesterolemia, are currently considered as
      possible immunomodulatory agents. Statins inhibit the production of
      proinflammatory cytokines and reduce the expression of several immunoregulatory
      molecules, including major histocompatibility complex class II (MHC-II)
      molecules. In this study, we investigated the mechanism by which simvastatin
      reduces the membrane expression of MHC-II molecules on several human cell types.
      We demonstrate that the reduction of MHC-II membrane expression by simvastatin
      correlates with disruption of cholesterol-containing microdomains, which
      transport and concentrate MHC-II molecules to the cell surface. In addition, we
      demonstrate that statins reduce cell-surface expression of other immunoregulatory
      molecules, which include MHC-I, CD3, CD4, CD8, CD28, CD40, CD80, CD86, and CD54.
      Our observations indicate that the downregulation of MHC-II at the cell surface
      contributes to the immunomodulatory properties of statins and is achieved through
      disruption of cholesterol-containing microdomains, which are involved in their
      intracellular transport.

PMID- 15993712
TI  - Natural evolution of a human virus-specific antibody gene repertoire by somatic
      hypermutation requires both hotspot-directed and randomly-directed processes.
AB  - Somatic hypermutation of antibody genes is mediated by activation-induced
      cytidine deaminase and targets primarily hotspot motifs. We tested the hypothesis
      that the antibody variable genes of virus-specific B cells from infants exhibit a
      decreased frequency of somatic mutations compared with adults. We also sought to
      determine whether virus-specific B cells exhibit predominantly hotspot or
      randomly directed processes. We analyzed somatic mutations in rotavirus (RV)
      specific B cells from otherwise healthy but recently RV-infected infants or
      adults in comparison with B cells from healthy volunteers not recently infected.
      We compared these antibody variable gene sequences with those derived from RV
      specific B cells from an adult patient with X-linked hyper-IgM syndrome (XHIM).
      We found that the overall mutational frequency within the antibody variable
      region was lowest in RV-specific B cells from RV-infected infants, followed by
      randomly selected B cells, followed by RV-specific B cells from the patient with
      XHIM. RV-specific memory B cells from healthy adults exhibited the highest
      frequency of mutations. Approximately half of mutations in random or RV-specific
      B cells from adults or infants occurred at the DGYW/WRCH or WA/TW hotspot motifs.
      These findings suggest that virus-specific antibodies require both hotspot and
      randomly-directed processes.

PMID- 15993713
TI  - Coculture of Th cells with interleukin (IL)-7 in the absence of antigenic stimuli
      induced T-cell anergy reversed by IL-15.
AB  - Interleukin-7 (IL-7) is an important survival factor for T cells. We report here
      for the first time that it has another important role, facilitating T-cell clonal
      unresponsiveness, or anergy. The anergy was induced by a 20-day coculture of
      activated-human CD4(+) T-cell clones with IL-7 and irradiated peripheral blood
      mononuclear cells without antigenic stimuli. T-cell survival, but not T-cell
      anergy induction, was dependent on direct cell contacts between T cells and
      irradiated peripheral blood mononuclear cells. The anergic T cells exhibited no
      or very low expression of IL-7 receptor alpha chain (IL-7Ralpha), IL-2 receptor
      alpha chain (IL-2Ralpha), and common gamma chain (gammac), and did not express
      cytotoxic T-lymphocyte-associated protein 4, but expressed IL-15Ralpha. Coculture
      for 3 to 9 days of anergic T cells with a T-cell-activating cytokine IL-15, but
      not IL-2, restored the responsiveness of IL-7-induced anergic T cells together
      with reexpressions of IL-7Ralpha, IL-2Ralpha, and gammac. The anergy induction by
      IL-7 and restoration of responsiveness by IL-15 suggest novel mechanisms for
      regulation of helper T-cell responses, induction of peripheral tolerance, and
      breakdown of T-cell self-tolerance.

PMID- 15993714
TI  - Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G-
      possible implications for human reproduction and autoimmune disease.
AB  - A line of investigation indicates that one or several genes in the human major
      histocompatibility complex (MHC) influences reproductive success. Studies have
      revealed associations between human leukocyte antigen (HLA) class II genes and
      risk of recurrent spontaneous abortion (RSA) and pre-eclampsia. However, these
      genes are not expressed at the feto-maternal interface. Furthermore, associations
      between polymorphisms in the nonclassical HLA class Ib gene, HLA-G, and
      reproductive outcome have been demonstrated. HLA-G is expressed by extravillous
      trophoblast during pregnancy, making it a more obvious candidate gene for a
      possible influence on pregnancy outcome. HLA-G has immunomodulatory functions. We
      have studied linkage disequilibrium between HLA class II genes, primarily HLA
      DRB1 alleles, and HLA-G alleles in women with RSA and their partners (n = 103)
      and in control women and their partners (n = 92). We found a significant linkage
      disequilibrium between HLA-DR3 and HLA-G*010102 in both the RSA and control
      populations. For all four studied HLA loci, the alleles in the haplotype HLA
      DRB1*03.DQA1*05.DQB1*02.G*010102 was in clear linkage disequilibrium. This HLA
      haplotype has repeatedly been associated with different autoimmune diseases but
      also with RSA. The G*010102 allele includes a 14-bp sequence polymorphism in the
      3' untranslated region of the gene, which has been associated with differences in
      HLA-G mRNA alternative splicing and stability. This 14-bp polymorphism has also
      been associated with RSA, pre-eclampsia, and outcome of in vitro fertilization.
      Implications of HLA polymorphism--and other polymorphic genes in the MHC for
      pregnancy outcome--and for autoimmune diseases during pregnancy are discussed.

PMID- 15993715
TI  - IL-6 and IL-10 promoter gene polymorphisms of patients and donors of allogeneic
      sibling hematopoietic stem cell transplants associate with the risk of acute
      graft-versus-host disease.
AB  - The present study aimed to determine existing associations between single
      nucleotide polymorphisms within the promoters of interleukin (IL)-6 (-174 G/C)
      and IL-10 (-1082 G/A, -819 C/T, -592 C/A) genes and the outcome of allogeneic
      sibling hematopoietic stem cell transplantation. Ninety-three recipients and 74
      donors were typed for IL-6 and IL-10 alleles by polymerase chain reaction
      sequence specific primer. Then, IL-6 activity in patient serum and the
      concentration of C-reactive protein were analyzed at various times after
      transplantation in relation to transplant complications and IL-6 genotype. IL-6
      activity in serum was significantly higher in patients who died as a result of
      toxic complications and after the 6 weeks after transplantation in patients with
      severe acute graft-versus-host disease (aGVHD). Recipient IL-6 G genotype was
      associated with increased IL-6 activity and C-reactive protein production. In
      univariate analyses, recipient IL-6 G and donor IL-6 GG associated or tended to
      associate with increased risk for aGVHD. In contrast, recipient IL-10 GCC/GCC and
      donor IL-10 ACC decreased the risk of aGVHD. IL-6 and IL-10 polymorphic features,
      together with other factors known to affect the risk of aGVHD, were also
      subjected to multivariate analyses. These analyses confirmed the independent
      contribution of recipient IL-10 GCC/GCC (odds ratio = 0.085, p = 0.046) and donor
      IL-6 GG (odds ratio = 3.934, p = 0.034) genotypes to the risk of aGVHD.

PMID- 15993716
TI  - Interleukin 12 (IL12B) and interleukin 12 receptor (IL12RB1) gene polymorphisms
      in rheumatoid arthritis.
AB  - The aim of this study was to assess the possible association between the IL12B
      and the IL12RB1 gene polymorphisms and the systemic autoimmune disease rheumatoid
      arthritis (RA). Our study population consisted of 545 patients with RA and 393
      healthy subjects. All the individuals were of white Spanish origin. Genotyping of
      the IL12B (IL12Bpro and IL12B 3' untranslated region) and IL12RB1 (641A-->G,
      1094T-->C, and 1132G-->C) polymorphisms was performed by polymerase chain
      reaction-restriction fragment length polymorphism and polymerase chain reaction
      fluorescent methods. No statistically significant differences in the distribution
      of the IL12B and the IL12RB1 genotypes and alleles between patients with RA and
      control subjects were observed. In addition, no association was found between the
      above-mentioned polymorphisms with any of the demographic and clinical parameters
      tested in patients with RA. These results suggest that IL12B and IL12RB1 genes
      may not play a relevant role in the susceptibility or severity of RA in the
      Spanish population.

PMID- 15993717
TI  - Association of the matrix metalloproteinase-3 (MMP-3) promoter polymorphism with
      celiac disease in male subjects.
AB  - Matrix metalloproteinases (MMPs), such as stromelysin-1 (MMP-3), are a family of
      enzymes important in resorption and remodeling of the extracellular matrix whose
      degradation may play a role in the villous atrophy characteristic of celiac
      disease (CD). We investigated the association between the polymorphism at
      position -1171 of the MMP-3 gene and susceptibility to CD in 225 Italian patients
      and 170 controls previously typed for human leukocyte antigen (HLA) class II
      genes. We also evaluated sex differences in the effect of this polymorphism on
      disease risk. A male-specific association of the 5A/6A polymorphism with CD was
      observed. The frequencies of 6A allele and 6A/6A genotype in affected male
      subjects were significantly above those observed both in male controls (p = 4.1 x
      10(-3) and p = 3.4 x 10(-3); odds ratio = 2.4, 95% confidence interval 1.3-4.3)
      and in female patients (p = 2.7 x 10(-4) and p = 6.2 x 10(-4)). This is the first
      demonstration of a sex-specific association between the MMP-3 promoter
      polymorphism and CD. Homozygosity for the 6A allele appears as a risk factor for
      CD only in men, which is different from the HLA susceptibility alleles that
      confer a higher risk in women.

PMID- 15993718
TI  - Listing of common HLA alleles and haplotypes based on the study of 356 families
      residing in the Paris, France, area: implications for unrelated hematopoietic
      stem cell donor selection.
AB  - In this study we have identified frequent human leukocyte antigen (HLA)-A, -B, 
      C,-DRB1, and -DQB1 alleles, frequent HLA-B/C, HLA-DRB1/DQB1 two-allele
      associations, and the most common HLA-A/B/C/DRB1/DQB1 five-locus haplotypes in a
      population residing in the Paris, France, area. The study was carried out in 356
      families of children awaiting hematopoietic stem-cell transplantation (HSCT),
      with the selection criterion that haplotypes could be assigned with certainty to
      both the patient and at least one parent. Parental haplotypes were HLA-A, -B
      serologically typed, and HLA-C, -DRB1, -DQB1 broadly typed by polymerase chain
      reaction-sequence-specific oligonucleotide probe. The alleles of the most
      frequent haplotypes were subsequently defined at a high-resolution level by
      polymerase chain reaction-sequence-specific primer. The results on the
      distribution of common alleles and common allele associations demonstrated
      similarities with the previously published data in Caucasian populations, as
      expected from the geographic origin of the studied population. More importantly,
      this study provides the largest listing of common B/C and DRB1/DQB1 associations
      and of common five-allele haplotypes defined with certainty in a Caucasian
      population to date. These results can be used to help estimate the likelihood of
      finding a suitable donor in unrelated HSCT and to delineate search strategies for
      potential donors.

PMID- 15993719
TI  - Novel substitution polymorphisms of human immunoglobulin VH genes in Mexicans.
AB  - It has been proposed that the defense and recognition functions of the immune
      system, especially those mediated by antibodies, require a great diversity of
      receptors. Nonetheless, functional and structural evidence has demonstrated the
      presence of restrictions, both in the use of the repertoire and in the
      recognition of antigens. Fifty-one functional genes have been described in the
      IghV locus; however, there is a variety of evidences indicating that only a small
      fraction of the immunoglobulin genes plays a central role in determining the
      fundamental properties of the antibody repertoire of the immune system. On the
      basis of this functional and structural information, we selected four IghV genes
      and characterized their polymorphism in a sample of Mexican individuals. We also
      analyzed the implications for the recognition mechanism of the substitutions
      found in the sequenced alleles. We found that diversification through allelism
      varies from segment to segment, both in the amount of alleles encountered and in
      the nature and distribution of mutations in the codifying zone, which might
      depend on its importance for the repertoire. Such functional characteristics may
      be useful in the interpretation of differential gene usage in certain
      physiological, ontological, and/or pathological conditions.

PMID- 15993720
TI  - Association of HLA-DR and -DQ genes with Graves disease in Koreans.
AB  - Graves disease (GD) is an autoimmune thyroid disease and is associated with human
      leukocyte antigen (HLA)-DR3 and DQA1*0501 in Caucasians. However, the association
      of HLA with GD is less clear-cut in East Asian populations. We analyzed HLA-DRB1
      and -DQB1 associations with GD in 198 Korean patients compared with 200 healthy
      controls. HLA-DRB1*0803 (27.8% vs. 14.5% in controls, OR = 2.27, corrected p
      [p(c)] = 0.03) and *1602 (5.1% vs. 0%, OR = 22.34, p(c) = 0.03) alleles and
      closely linked haplotypes, DRB1*0803-DQB1*0601 and DRB1*1602-DQB1*0502, conferred
      susceptibility to GD in Koreans. Weak association of DRB1*0301 with GD
      susceptibility was observed in male patients only (12.5% vs. 3.5%, OR = 3.57, p <
      0.05). HLA-DRB1*0101, *0701, *1202, and *1302 alleles were weakly associated with
      resistance to the disease (OR < 0.5, p < 0.05). Some HLA alleles were weakly
      associated with clinical characteristics in GD patients. Patients with DRB1*1301
      DQB1*0603 developed their diseases in younger ages and were more frequently
      associated with larger goiter (p < 0.05). Although HLA class II alleles
      associated with GD in Koreans were different from those in Caucasians, some
      associations are shared, such as association of DRB1*0301 in male patients and
      protective effect of DRB1*0701 to GD susceptibility.

PMID- 15993722
TI  - Resuscitation great: John hunter-surgeon and resuscitator.

PMID- 15993723
TI  - Ventricular fibrillation is not provoked by chest compression during post-shock
      organized rhythms in out-of-hospital cardiac arrest.
AB  - INTRODUCTION: It has been proposed that chest compression (CC) can provoke
      recurrent ventricular fibrillation (VF) after defibrillation has restored an
      organized rhythm (OR). If so this would have major implications for proposed
      changes in resumption of CC after defibrillation, regardless of rhythm. The aim
      of this study was to examine our defibrillation data for evidence of post-shock
      CC-induced VF. METHODS: In a defibrillation program using police/fire personnel
      entire electrocardiograms (ECGs) from defibrillator data cards were examined for
      initial and post-shock rhythms and CC artifact. Successful shock rhythms were
      defined as either asystole or OR in the first five seconds post-shock, the latter
      as at least two QRS complexes during this time period. Artifact from CC was
      assessed for association with recurrent VF during either asystole or OR. RESULTS:
      Among 67 patients (pts) defibrillated by police/fire personnel VF recurred at
      least once in 35 (52%). Entire ECGs were available in 32 of these 35 pts. Chest
      compression-associated recurrent VF developed in 16 of 32 patients (50%). A total
      of 78 VF recurrences were observed during the period prior to administration of
      epinephrine (adrenaline) or other drugs. During post-shock asystole VF recurred
      32 times (41% of all recurrent VF episodes); in 19 (59%) VF recurred during CC
      and in 13 (41%) it was spontaneous. During OR VF recurred 46 times (59% of all
      recurrent VF episodes); in 36 (78%) VF recurred spontaneously and in only 10
      (22%) during CC. Heart rate preceding spontaneous recurrence of VF during OR was
      84+/-35 beats/min, and heart rate preceding CC-associated VF recurrence during OR
      was 46+/-20 beats/min (p > 0.001). There was no statistically significant
      difference in the width of the QRS complex preceding VF recurrence in the CC
      associated and spontaneous VF recurrence groups (p = 0.925). CONCLUSIONS: VF
      recurred following successful shocks in 52% of pts. With asystole VF recurred
      frequently during CC. However, during post-shock OR VF recurred unrelated to CC
      in most instances. Thus, resumption of CC immediately after shocks that restore
      an OR is unlikely to provoke recurrent VF, and resumption of CC need not be
      delayed.

PMID- 15993724
TI  - Effect of an inspiratory impedance threshold device on hemodynamics during
      conventional manual cardiopulmonary resuscitation.
AB  - BACKGROUND: In animals in cardiac arrest, an inspiratory impedance threshold
      device (ITD) has been shown to improve hemodynamics and neurologically intact
      survival. The objective of this study was to determine whether an ITD would
      improve blood pressure (BP) in patients receiving CPR for out-of-hospital cardiac
      arrest. METHODS: This prospective, randomized, double-blind, intention-to-treat
      study was conducted in the Milwaukee, WI, emergency medical services (EMS)
      system. EMS personnel used an active (functional) or sham (non-functional) ITD on
      a tracheal tube on adults in cardiac arrest of presumed cardiac etiology. Care
      between groups was similar except for ITD type. Low dose epinephrine (1mg) was
      used per American Heart Association Guidelines. Femoral arterial BP (mmHg) was
      measured invasively during CPR. RESULTS: Mean+/-S.D. time from ITD placement to
      first invasive BP recording was approximately 14 min. Twelve patients were
      treated with a sham ITD versus 10 patients with an active ITD. Systolic BPs
      (mean+/-S.D.) [number of patients treated at given time point] at T = 0 (time of
      first arterial BP measurement), and T=2, 5 and 7 min were 85+/-29 [10], 85+/-23
      [10], 85+/-16 [9] and 69+/-22 [8] in the group receiving an active ITD compared
      with 43+/-15 [12], 47+/-16 [12], 47+/-20 [9], and 52+/-23 [9] in subjects treated
      with a sham ITD, respectively (p < 0.01 for all times). Diastolic BPs at T = 0,
      2, 5 and 7 min were 20+/-12, 21+/-13, 23+/-15 and 25+/-14 in the group receiving
      an active ITD compared with 15+/-9, 17+/-8, 17+/-9 and 19+/-8 in subjects treated
      with a sham ITD, respectively (p = NS for all times). No significant adverse
      device events were reported. CONCLUSIONS: Use of the active ITD was found to
      increase systolic pressures safely and significantly in patients in cardiac
      arrest compared with sham controls.

PMID- 15993725
TI  - The use of laryngeal tube by nurses in out-of-hospital emergencies: preliminary
      experience.
AB  - In out-of-hospital emergencies, including cardiac arrest, securing the airway and
      providing adequate lung ventilation are of paramount importance. Tracheal
      intubation is perceived as the gold standard technique and it is recommended by
      International Guidelines, but non skilled personnel often find the procedure
      difficult to achieve. Supraglottic devices are a good alternative in these
      situations, because they are superior to a bag-valve-mask for lung ventilation
      and offer better protection from aspiration. We have tested the laryngeal tube
      (LT) in out-of-hospital emergencies by minimally trained nurses. The LT was
      placed in 30 patients in cardiac arrest. LT insertion was successful within two
      attempts in 90% of patients, and ventilation was adequate in 80% of cases. No
      regurgitation occurred in any patient. The laryngeal tube remained in the correct
      position throughout resuscitation attempts in 93.3% of cases, while in two
      patients (6.6%) it became dislodged. In a subjective evaluation of the manoeuvre
      by nurses (ease of insertion, adequacy of ventilation, protection from
      aspiration), 86.7% of them expressed a positive opinion. The laryngeal tube
      appeared to be a reliable device for nurses to manage the airway in out-of
      hospital emergencies.

PMID- 15993726
TI  - Twelve-month retention of CPR skills with automatic correcting verbal feedback.
AB  - AIM: To evaluate the retention of CPR skills 12 months after initial training,
      using a manikin equipped with a computer-based voice advisory feedback system.
      METHODS: Thirty-five volunteers had individual 20 min training sessions without
      an instructor on a manikin with computer-based voice advisory feedback. The
      feedback depended on the performance as measured by the manikin computer system
      versus set limits for ventilation and compression variables. Twelve of the
      volunteers received additional ten 3-min self-training sessions during the
      following month making a total of 50 min training. All ventilation and
      compression variables when the volunteers were tested before, immediately after
      and 6 months after training have previously been reported. The volunteers were
      now tested 12 months after the initial training session with activated feedback.
      RESULTS: There were virtually no changes in CPR skills when tested with active
      feedback 12 months after initial training versus immediately or 6 months post
      training. The only exception was a slightly lower number of compressions per
      minute at 12 months versus immediate post-training in the subgroup with 20 min of
      initial training, 47+/-4 versus 52+/-4, p = 0.008. There were no differences
      between the 20 and 50 min training subgroups at 12 months. CONCLUSIONS: Computer
      based voice advisory feedback can improve the performance of basic life support
      skills on a manikin with no deterioration in feedback supported performance after
      12 months.

PMID- 15993727
TI  - Attenuated pediatric electrode pads for automated external defibrillator use in
      children.
AB  - OBJECTIVE: This post-market, observational study is intended to evaluate reported
      uses of pediatric pads that reduce the energy delivered by some adult automated
      external defibrillators (AEDs) so that they may be used with pediatric patients.
      METHODS: Users of the pediatric pads were asked to report any use of the pads,
      even if no shock was delivered and to provide detailed information about the
      event, caregiver and the patient. RESULTS: Reports of the use of pediatric pads
      have been received and confirmed for 27 patients, age range 0 days to 23 years,
      median 2 years. Ventricular fibrillation (VF) was reported in eight cases, age
      range 4.5 months to 10 years, median 3 years. Shocks were delivered to all VF
      patients, the average shock number was 1.9, range 1-4. All patients had
      termination of VF, were admitted to the hospital and five survived to hospital
      discharge. Non-shockable rhythms were reported in 16 patients, and the AED
      appropriately did not advise a shock. Eleven of these patients had asystole or
      PEA as their initial rhythm and did not survive to hospital discharge. One report
      contained no additional information other than that the patient did not survive,
      and in two other reports, the pads were not applied to patients. CONCLUSIONS:
      Voluntary reports of the use of attenuated pediatric defibrillation pads indicate
      the devices performed appropriately. All eight VF patients had termination of VF
      and five survived to hospital discharge. These data support the rapid deployment
      of AEDs for young children as well as adolescents and adults. Since the pediatric
      pads are available and deliver an appropriate dose for children, their use should
      be strongly encouraged.

PMID- 15993728
TI  - Haemodynamic effects of mental stress during cardiac arrest simulation testing on
      advanced life support courses.
AB  - We investigated the haemodynamic response to the mental stress induced by being
      evaluated as a team leader in simulated advanced life support (ALS) scenarios.
      METHODS: Healthcare providers participating as candidates to ALS courses were
      monitored while acting as team leaders in a cardiac arrest testing scenario
      (CASTest). Heart rate (HR), systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) were measured before, during and after the CASTest. The
      correlation between the haemodynamic responses and sex, age, body mass index
      (BMI) and marks on course multiple choice questions (MCQs) were studied using
      multiple linear regression. RESULTS: Eighty-eight subjects (46 women, 42 men,
      mean age 34.9+/-6.8 years) were enrolled. Mean HR, SBP and DBP increased
      significantly during the CASTest and reached a peak after a phase of the scenario
      which included an unsuccessful defibrillation. Ten minutes after the CASTest, HR,
      SBP and DBP were still significantly higher than their respective baseline
      values. A significant positive correlation was found between the DBP and SBP
      response during the scenario and the BMI, and between the DBP response and the
      candidates' age. The haemodynamic stress response was neither correlated with the
      candidates' marks in the course MCQ nor with their instructor potential (IP).
      CONCLUSION: During the testing scenario the ALS candidates showed a significant
      haemodynamic response to mental stress, which depended mainly on their age and
      BMI rather than on their knowledge and skills.

PMID- 15993729
TI  - The development and implementation of a multidisciplinary neonatal resuscitation
      team in a Canadian perinatal centre.
AB  - PURPOSE: To describe the implementation of a multidisciplinary neonatal
      resuscitation team (NRT) at a Canadian tertiary perinatal centre. METHODS: In
      February 2002, the primary role of neonatal resuscitation was transferred from
      attending physicians (on-call off-site) to a NRT (consisting of a neonatal
      intensive care nurse, a respiratory therapist, and, when available, a resident,
      clinical associate (supervised licensed physician), or nurse practitioner). The
      NRT attended moderate- and high-risk deliveries (in the latter case, accompanied
      by a neonatologist). Normal, low-risk deliveries remained the responsibility of
      caseroom (delivery room) staff, assisted by the NRT when concerns arose. A
      prospective assessment was performed of resuscitation requirements and outcomes.
      RESULTS: : Over 24 months, the NRT attended 2944 (64.5%) out of 4565 deliveries.
      The NRT attended 2497 moderate-risk deliveries, providing positive pressure
      ventilation (in 15.7% of cases), chest compressions (0.1%), and epinephrine
      (adrenaline) (0.08%). There were no neonatal deaths or morbidities related to
      resuscitation in this cohort. A small, but significant, proportion of babies with
      no identifiable risk factors required resuscitation by caseroom staff (in most
      cases with brief periods of positive pressure ventilation). CONCLUSION:
      Assignment of level of risk provides a safe means of delivering neonatal
      resuscitation services, facilitating NRT attendance at the majority of deliveries
      that required resuscitation. A NRT can perform safely and effectively in a
      tertiary perinatal centre with off-site support from experienced neonatal staff
      at high-risk deliveries only. Caseroom (delivery room) staff should continue to
      be trained in neonatal resuscitation.

PMID- 15993730
TI  - Evaluation of out-of-hospital cardiopulmonary resuscitation with resuscitative
      drugs: a prospective comparative study in Japan.
AB  - OBJECTIVE: This study aimed at evaluating two emergency medical service systems,
      one in which emergency life-saving technicians (ELSTs) are allowed to administer
      epinephrine (adrenaline) to patients with out-of-hospital cardiac arrest and one
      in which ELSTs are allowed to administer epinephrine, lidocaine, and atropine.
      METHODS: A modified, prospective community health trial was conducted from April
      1 to October 31, 2003. Areas served by physician-manned ambulances, where out-of
      hospital cardiopulmonary resuscitation (CPR) was performed with resuscitative
      drugs (experimental areas), were compared to areas served by ELST-manned
      ambulances, where resuscitative drugs were not administered outside the hospital
      (reference areas). The sequence of emergency procedures performed in the
      experimental areas was divided into three phases. Phase I included administration
      of epinephrine, which simulated administration of epinephrine by ELSTs. Phase II
      started with the use of lidocaine or atropine. Phases I and II simulated
      administration of epinephrine, lidocaine, and atropine by ELSTs. Phase III began
      with administration of another drug. Outcomes, resuscitation rates and 1-month
      survival rates were determined, and differences between the two types of areas
      were analyzed. RESULTS: For non-traumatic cardiac arrest, outcomes through phase
      II in the experimental areas were significantly better than those in the
      reference areas. Phase I-only outcomes in the experimental areas were better, but
      not significantly better, than those in the reference areas. CONCLUSION: Use of
      resuscitative drugs for non-traumatic prehospital CPR appears to be effective in
      terms of resuscitation rates and 1-month survival rates.

PMID- 15993731
TI  - Management of septic shock with a norepinephrine-based haemodynamic algorithm.
AB  - Management of septic shock (SS) with a norepinephrine (noradrenaline)-based
      haemodynamic algorithm. INTRODUCTION: The choice of the best vasopressor for
      haemodynamic management of septic shock is controversial. Nevertheless, very few
      studies have been focused on evaluating different management algorithms. The aim
      of this study was to evaluate the performance of a norepinephrine (NE)-based
      management protocol. Experience with NE as the initial vasopressor, even if not
      comparative, could bring relevant data for planning future trails. We also wanted
      to evaluate the compliance of critical care physicians and nurses with
      haemodynamic management protocol. PATIENTS AND METHOD: A norepinephrine-based
      algorithm for the management of septic shock that commands different sequential
      interventions according to its requirements, was applied prospectively to 100
      consecutive septic shock patients. RESULTS: Norepinephrine was used as the first
      vasoactive drug in all patients with a maximum dose of 0.31+/-0.3 microg kg(
      1)min(-1) and an ICU mortality of 33%. Physicians applied correctly all the steps
      of the algorithm in 92% of the patients. Applying the algorithm, avoided the use
      of pulmonary artery catheter in 31 patients and led to use of lower doses of
      vasoactive agents than in many other clinical experiences. CONCLUSION: In
      conclusion, our data support extended use of an algorithm based on norepinephrine
      for treating septic shock patients. This is the first clinical study that uses NE
      as the initial vasopressor drug systematically, and although not comparative, the
      mortality rates adjusted to APACHE II, are comparable to other studies. It also
      gives support for future clinical trials comparing norepinephrine with dopamine
      in this setting.

PMID- 15993732
TI  - Pyruvate improves cardiac electromechanical and metabolic recovery from
      cardiopulmonary arrest and resuscitation.
AB  - Severe depletion of myocardial energy and antioxidant resources during cardiac
      arrest culminates in electromechanical dysfunction following recovery of
      spontaneous circulation (ROSC). A metabolic fuel and natural antioxidant,
      pyruvate augments myocardial energy and antioxidant redox states in parallel with
      its enhancement of contractile performance of stunned and oxidant-challenged
      hearts. This study tested whether pyruvate improves post-arrest cardiac function
      and metabolism. Beagles were subjected to 5 min cardiac arrest and 5 min open
      chest cardiac compression (OCCC: 80 compressions min(-1); aortic pressure 60-70
      mmHg), then epicardial dc countershocks (5-10 J) were applied to restore sinus
      rhythm. Pyruvate was infused i.v. throughout OCCC and the first 25 min ROSC to a
      steady-state arterial concentration of 3.6+/-0.2 mM. Control experiments received
      NaCl infusions. Phosphocreatine phosphorylation potential (approximately PCr) and
      glutathione/glutathione disulfide ratio (GSH/GSSG), measured in snap-frozen left
      ventricle, indexed energy and antioxidant redox states, respectively. In control
      experiments, left ventricular pressure development, dP/dt and carotid flow
      initially recovered upon defibrillation, but then fell 40-50% by 3 h ROSC. ST
      segment displacement in lead II ECG persisted throughout ROSC. Approximately PCr
      collapsed and GSH/GSSG fell 61% during arrest. Both variables recovered partially
      during OCCC and completely during ROSC. Pyruvate temporarily increased
      approximately PCr and GSH/GSSG during OCCC and the first 25 min ROSC and enhanced
      pressure development, dP/dt and carotid flow at 15-25 min ROSC. Contractile
      function stabilized and ECG normalized at 2-3 h ROSC, despite post-infusion
      pyruvate clearance and waning of its metabolic benefits. In conclusion,
      intravenous pyruvate therapy increases energy reserves and antioxidant defenses
      of resuscitated myocardium. These temporary metabolic improvements support post
      arrest recovery of cardiac electromechanical performance.

PMID- 15993733
TI  - The effect of non-insulin dependent diabetes mellitus on uncontrolled hemorrhage
      in a rodent model.
AB  - OBJECTIVE: Diabetes mellitus (DM) is an independent risk factor for higher
      morbidity and mortality rates from trauma. We tested the null hypothesis that
      there would be no difference in the hemorrhage volumes and hemodynamic responses
      to uncontrolled hemorrhage between Zucker Diabetic Fat rats (ZDF) and euglycemic
      Sprague-Dawley rats (SD). METHODS: Twenty-four adult male rats (12 ZDF and 12 SD)
      were anesthetized with althesin via the intraperitoneal route. The femoral artery
      was cannulated by cut-down to monitor the heart rate (HR), mean arterial pressure
      (MAP) and to obtain blood samples for blood gas analysis. Twelve rats (6 ZDF and
      6 SD) underwent uncontrolled hemorrhage by 50% tail amputation. Twelve rats (6
      ZDF and 6 SD) served as non-hemorrhage controls. The HR, MAP, lactate (LAC),
      glucose levels (GL) and cumulative hemorrhage volume (CHV) were measured pre
      hemorrhage and then every 15 min post-hemorrhage for 120 min. Data were reported
      as mean+/-S.E.M. Group comparisons were analyzed by ANOVA with repeated values;
      post hoc testing by Bonferroni (all tests were two-tailed, alpha = 0.05).
      RESULTS: Pre-hemorrhage the SD and ZDF were evenly matched for LAC, HR and MAP.
      CHV (cm3/100 g) was significantly (p = 0.008) greater in the ZDF (1.49+/-0.12) as
      compared to the SD (0.38+/-0.11). The ZDF had significantly (p < 0.001) higher
      LAC (7.96+/-0.61 mmol/L) than the SD (2.0+/-0.41 mmol/L). CONCLUSION: DM as
      compared to non-DM rats suffered a greater blood loss with a more severe lactic
      acidosis after a comparable uncontrolled vascular injury.

PMID- 15993734
TI  - Echocardiographic comparison of cardiopulmonary resuscitation (CPR) using
      periodic acceleration (pGz) versus chest compression.
AB  - OBJECTIVE: This investigation compared the effects of conventional
      cardiopulmonary resuscitation (CPR) using an automated Thumper chest compression
      device to periodic acceleration CPR (pGz-CPR) on early post-resuscitation
      ventricular function assessed by echocardiography, in an adult pig model of CPR.
      BACKGROUND: Whole body periodic acceleration along the spinal axis (pGz) is a new
      method of cardiopulmonary resuscitation (CPR). Biomechanical forces and
      biochemical release produced by pGz impart ventilation and increase blood flow.
      Our laboratory has reported normal neurological and cardiovascular function 48 h
      after return of spontaneous circulation in animals that have undergone 22 min of
      pGz-CPR. METHODS: Ventricular fibrillation (VF) was induced in 16 animals (25-35
      kg). After 3 min of non-interventional period, the animals were randomized to
      receive either pGz-CPR or Thumper-CPR for 15 min. After 18 min of VF, a single
      dose of vasopressin and bicarbonate were administered and defibrillation
      attempted. An echocardiogram was performed at baseline and serially for 6h.
      Ejection fraction (EF), fractional shortening (FS) and wall motion were assessed
      by 2D and M-mode echocardiography. RESULTS: Return of spontaneous circulation to
      360 min occurred in 5/8 (62%) of the animals receiving Thumper-CPR and in 7/8
      (88%) receiving pGz-CPR. FS and EF were impaired after CPR, but pGz-CPR animals
      had less impairment than Thumper-CPR animals. Further, wall motion score index
      (WMSI) was more impaired after Thumper-CPR and remained as such even 6h post-CPR.
      CONCLUSION: pGz holds promise as a new method for CPR with better left
      ventricular (LV) function post-CPR than the more traditional chest compression
      method.

PMID- 15993735
TI  - Thoracic lavage in accidental hypothermia with cardiac arrest--report of a case
      and review of the literature.
AB  - BACKGROUND: Accidental hypothermia resulting in cardiac arrest poses numerous
      therapeutic challenges. Cardiopulmonary bypass (CPB) should be used if feasible
      since it optimally provides both central rewarming and circulatory support.
      However, this modality may not be available or is contraindicated in certain
      cases. Thoracic lavage (TL) provides satisfactory heat transfer and may be
      performed by a variety of physicians. This paper presents the physiological
      rationale, technique, and role for TL in accidental hypothermia with cardiac
      arrest. METHODS: A patient with hypothermic cardiac arrest, treated by the author
      using TL, serves as the basis for this report. A search of the English language
      literature using PubMed (National Library of Medicine, Bethesda, Maryland) was
      conducted from 1966 to 2003 and 13 additional patients were identified.
      Demographic information, lavage method, rewarming rate, complications, and
      neurological outcome were analysed. RESULTS: There were numerous causes for
      hypothermia, with drug and alcohol intoxication being the most common (n = 4;
      28.6%). Patient age ranged from 8 to 72 years (median = 36 years). Mean core
      temperature was 24.5+/-0.60 degrees C. Most patients were without blood pressure
      or pulse upon presentation to the Emergency Department and the predominant
      cardiac rhythm was ventricular fibrillation (VF) (n = 9; 64.3%). Thoracic lavage
      was accomplished by thoracotomy in seven patients and tube thoracotomy in the
      remaining seven. Median rewarming rate was 2.95 degrees C/h. Median time until
      sinus rhythm was restored was 120 min. Median length of hospital stay was 2
      weeks. Four (28.6%) patients died. Complications were seen in 12 (85.7%)
      patients. Among survivors, neurological outcome was normal in 8 (80%) while two
      were left with residual impairments. CONCLUSIONS: Patients presenting in cardiac
      arrest from accidental hypothermia may be rewarmed effectively using TL. Among
      survivors, normal neurological recovery is seen. Thoracic lavage should be
      strongly considered for these patients if CPB is not available or
      contraindicated.

PMID- 15993736
TI  - Influence of electromagnetic interference on the human electrocardiogram in
      automated external defibrillators.

PMID- 15993738
TI  - Non-pneumonic Klebsiella oxytoca myopericarditis simulating acute anterolateral
      myocardial infarction.

PMID- 15993739
TI  - Predicting outcome after cardiac arrest: two caveats.

PMID- 15993741
TI  - Methyl-parathion and organophosphorous pesticide metabolites modify the
      activation status and interleukin-2 secretion of human peripheral blood
      mononuclear cells.
AB  - Organophosphorous (OP) compounds are the most commonly used pesticides. There are
      reports on susceptibility to the toxic effects of OP pesticides, but no
      information exists regarding the toxicity of their metabolites. To determine the
      metabolites' contribution to the OP pesticide immunotoxic effects, human
      peripheral blood mononuclear cells (PBMCs) were treated with the parent compound
      methyl-parathion (MP) and the following OP pesticide alkyl-phosphorous
      metabolites: diethylphosphate (DEP), diethylthiophosphate (DETP),
      diethyldithiophosphate (DEDTP), dimethylphosphate (DMP), and
      dimethyldithiophosphate (DMDTP). Activation and function of the PBMCs were
      examined by assessment of phytohemagglutinin (PHA)-induced proliferative
      response, interleukin-2 (IL-2) secretion, and CD25 and CD69 expression.
      Treatments with DMP, DEP, DETP and DEDTP for 48h produced significant toxicity in
      human PBMCs, but did not affect their proliferative response to PHA. Only MP
      reduced cell proliferation by 30%. DEDTP decreased the proportion of PBMCs
      expressing CD25. This effect was associated with a reduction of IL-2 secretion,
      which was also reduced by MP and DMP treatments. In contrast, DETP and DEDTP
      treatments increased the expression of CD69. DMP, DETP and DEDTP were more
      consistently involved in modulating the PBMC response to PHA.

PMID- 15993742
TI  - Assessment of the in vivo genotoxicity of vanadate: analysis of micronuclei and
      DNA damage induced in mice by oral exposure.
AB  - Vanadium compounds are able to interact with living cells exerting a variety of
      biological effects. The pentavalent form is the most stable and toxic form of the
      element. In systems in vitro pentavalent vanadium is an effective genotoxic
      agent, inducing DNA damage and chromosome malsegregation at low doses. On the
      other hand, no adequate in vivo data are available for the characterization of
      the genotoxic hazard following oral intake, the most relevant route of human
      exposure. In this study, the genotoxic effects produced by the oral intake of
      sodium ortho-vanadate (Na(3)VO(4)) were investigated. Male CD-1 mice were treated
      for 5 weeks with a range of concentrations of Na(3)VO(4) in drinking water (0.75
      1500 mg/l). Both micronuclei and primary DNA lesions as detected by comet assay
      were assessed in several tissues. Statistically significant increases of
      micronuclei in bone marrow were observed in mice receiving the two highest
      concentrations of Na(3)VO(4) (750 and 1500 mg/l). A significant increase of comet
      tail length was observed in splenocytes of mice receiving Na(3)VO(4) at 1500
      mg/l, whereas no effect was observed in bone marrow and testis cells. No
      treatment-related effect on sperm chromatin structure or on testis cell
      population was observed. The determination of vanadium content in mouse tissues
      at the end of treatment highlighted a very low internal exposure, especially in
      soft tissues. Overall, the results obtained indicate that the genotoxic activity
      of pentavalent vanadium is expressed in vivo only following high dose exposure,
      possibly as a consequence of the poor bioavailability of the element.

PMID- 15993744
TI  - Repeated exposure to pyrrolidine-dithiocarbamate induces peripheral nerve
      alterations in rats.
AB  - Pyrrolidine-dithiocarbamate (PDTC), a synthetic compound widely used in cell
      biological investigations, recently attracted considerable interest as a putative
      anticancer agent. However, different dithiocarbamates have previously shown to
      cause neurological symptoms and morphological alterations in peripheral nerves.
      The purpose of the present study was to determine whether a 15-day oral
      administration with low doses of PDTC may produce adverse effects in peripheral
      nerves of rats. Female Wistar rats were assigned to receive PDTC [0.1, 0.5 or
      1.0mmol/(kg body weight/day)] by gavage for 15 days. Reduced conduction velocity
      was observed by electrophysiological analysis in tibial nerves of treated
      animals, accompanied by a marked decrease in Shwann cell S100-protein expression
      determined by immunohistochemistry. Electron microscopy evaluation revealed
      marked myelin degeneration in the fibers of treated animals. In particular, both
      morphological and electrophysiological data suggested an impairment of large,
      fast conducting fibers, whereas the smallest and slowest ones remained intact.
      However, the activity of plasma and liver alkaline-phosphatase, an enzymic marker
      of hepatic dithiocarbamate toxicity, was not altered by the treatment. The total
      contents of the redox-active metal copper increased in tibial nerves of treated
      rats and was accompanied by raised levels of lipid peroxidation products. This
      finding suggests a role for oxidative stress in the development of PDTC-induced
      pathological and functional alterations of tibial nerves. The observation that a
      15-day treatment with low doses of PDTC causes functional and morphological
      derangement of peripheral nerves advices against the possible use of this
      compound as a chemopreventive agent against cancer.

PMID- 15993743
TI  - Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic
      pathways in human oral keratinocytes and tissues.
AB  - Sanguinarine's use in human clinical applications is currently controversial.
      While some studies have demonstrated sanguinarine's anti-inflammatory and anti
      oxidant properties, other investigations reported sanguinarine's procarcinogenic
      effects. Like the tobacco-associated carcinogen, benzo(a)pyrene (B(a)P),
      sanguinarine is a polycyclic aromatic hydrocarbon (PAH). PAH exposure activates
      the aryl hydrocarbon transcription activating factor (AhR), resulting in nuclear
      translocation, binding to the aryl hydrocarbon nuclear translocator (ARNT), which
      thereby increases expression of a pool of carcinogen metabolizing enzymes. The
      goal of this study was to investigate whether sanguinarine activates this PAH
      associated signaling cascade in human oral cells and tissues. Our results
      demonstrate that sanguinarine: (i) results in formation of the AhR-ARNT complex,
      (ii) induces AhR-associated gene expression, (iii) inhibits cytochrome P450 1A1
      (CYP 1A1) microsomal oxidative activity and (iv) pretreatment upregulates CYP 1A1
      function. Collectively, these data provide evidence that sanguinarine activates
      PAH-associated signaling and metabolic pathways. Notably, previous studies have
      demonstrated that mammalian hepatic microsomes metabolize sanguinarine to a
      mutagenic epoxide. Persons who respond to sanguinarine exposure with induction of
      primarily Phase I relative to Phase II enzymes are, therefore, at risk for
      sanguinarine bioactivation and its potential mutagenic effects.

PMID- 15993745
TI  - Estrogenic and genotoxic potential of equol and two hydroxylated metabolites of
      Daidzein in cultured human Ishikawa cells.
AB  - The soy isoflavone daidzein (DAI) is known to undergo metabolism to equol (EQO)
      and to 3'-hydroxy-DAI (3'-HO-DAI) and 6-hydroxy-DAI (6-HO-DAI) in humans. In
      order to better understand the implications of soy diets for human health, the
      hormonal and genotoxic activities of these DAI metabolites were studied in
      cultured human endometrial carcinoma cells. When the estrogenicity was tested by
      cell-free binding to recombinant human estrogen receptor (ER) alpha and beta as
      well as by the induction of enzyme activity and gene expression of alkaline
      phosphatase (ALP) in Ishikawa cells, the ranking order was EQO>DAI>3'-HO-DAI>6-HO
      DAI. All compounds had a higher affinity to ERbeta than to ERalpha. No
      significant anti-estrogenic effects of the DAI metabolites were observed in the
      cells at non-cytotoxic concentrations. The in vitro genotoxicity was assessed by
      analyzing effects on cell cycle distribution and cell morphology as well as the
      induction of micronuclei (MN). EQO caused a slight increase in G1 and decrease in
      S phase of the cell cycle, and slightly but significantly induced kinetochore
      positive as well as kinetochore-negative MN and an elevated proportion of
      abnormal mitotic spindles. 3'-HO-DAI, but not 6-HO-DAI, induced kinetochore
      negative MN. The observation that major human metabolites of DAI exhibit
      estrogenic and genotoxic potential may be of relevance for the safety evaluation
      of diets containing soy isoflavones.

PMID- 15993746
TI  - Challenges in real-life emotion annotation and machine learning based detection.
AB  - Since the early studies of human behavior, emotion has attracted the interest of
      researchers in many disciplines of Neurosciences and Psychology. More recently,
      it is a growing field of research in computer science and machine learning. We
      are exploring how the expression of emotion is perceived by listeners and how to
      represent and automatically detect a subject's emotional state in speech. In
      contrast with most previous studies, conducted on artificial data with archetypal
      emotions, this paper addresses some of the challenges faced when studying real
      life non-basic emotions. We present a new annotation scheme allowing the
      annotation of emotion mixtures. Our studies of real-life spoken dialogs from two
      call center services reveal the presence of many blended emotions, dependent on
      the dialog context. Several classification methods (SVM, decision trees) are
      compared to identify relevant emotional states from prosodic, disfluency and
      lexical cues extracted from the real-life spoken human-human interactions.

PMID- 15993747
TI  - Cellular regulation and proposed biological functions of group VIA calcium
      independent phospholipase A2 in activated cells.
AB  - Mammalian cells contain several calcium-independent phospholipase A2 (PLA2)
      enzymes. The best studied of them is the so-called Group VIA PLA2 (iPLA2-VIA),
      which is an 85-88 kDa enzyme with unique structural features among the PLA2
      superfamily of enzymes, and has been found to play a key role in homeostatic
      membrane phospholipid metabolism in various cell types. Growing evidence suggests
      that, in addition to its homeostatic function, iPLA2-VIA may also play distinct
      roles in cellular signaling. This review focuses on the biochemical mechanisms
      that regulate the activity of iPLA2-VIA in activated cells, and the biological
      functions proposed for this enzyme during stimulus-response coupling.

PMID- 15993748
TI  - High-density growth arrest in Ras-transformed cells: low Cdk kinase activities in
      spite of absence of p27(Kip) Cdk-complexes.
AB  - The ras oncogene transforms immortalized, contact-inhibited non-malignant murine
      fibroblasts into cells that are focus forming, exhibit increased saturation
      density, and are malignant in suitable hosts. Here, we examined changes in cell
      cycle control complexes as normal and Ras-transformed cells ceased to grow
      exponentially, to reveal the molecular basis for Ras-dependent focus formation.
      As normal cells entered density-dependent arrest, cyclin D1 decreased while
      cyclin D2 was induced and replaced D1 in Cdk4 complexes. Concomitantly, p27(Kip1)
      levels rose and the inhibitor accumulated in both Cdk4 and Cdk2 complexes, as
      these kinases were inactivated. Ras-transformed cells failed to arrest at normal
      saturation density and showed no significant alterations in cell control
      complexes at this point. Yet, at an elevated density the Ras-transformed cells
      ceased to proliferate and entered a quiescent-like state with low Cdk4 and Cdk2
      activity. Surprisingly, this delayed arrest was molecularly distinct from contact
      inhibition of normal cells, as it occurred in the absence of p27(Kip1) induction
      and cyclin D1 levels remained high. This demonstrates that although oncogenic Ras
      efficiently disabled the normal response to contact inhibition, a separate back
      up mechanism enforced cell cycle arrest at higher cell density.

PMID- 15993749
TI  - Dissociation of beta-arrestin from internalized bradykinin B2 receptor is
      necessary for receptor recycling and resensitization.
AB  - Beta-arrestins are multifunctional adaptors that bind agonist-activated G protein
      coupled receptors (GPCRs), mediate their desensitization and internalization, and
      control the rate at which receptors recycle back at the plasma membrane ready for
      subsequent stimulation. The activation of the bradykinin (BK) type 2 receptor
      (B2R) results in the rapid desensitization and internalization of the receptor.
      Little is known, however, about the role of beta-arrestin in regulating the
      intracellular trafficking and the resensitization of the B2R. Using confocal
      microscopy, we show that BK stimulation of COS-7 cells expressing B2R induces the
      colocalization of the agonist-activated receptor with beta-arrestin into
      endosomes. Fluorescent imaging and ligand binding experiments also reveal that
      upon agonist removal, beta-arrestin rapidly dissociates from B2R into endosomes,
      and that receptors return back to the plasma membrane, fully competent for
      reactivating B2R signaling as measured by NO production upon a second BK
      challenge. However, when the receptor is mutated in its C-terminal domain to
      increase its avidity for beta-arrestin, B2R remains associated with beta-arrestin
      into endosomes, and receptors fail to recycle to the plasma membrane postagonist
      wash. Similarly, the recycling of receptors is prevented when a beta-arrestin
      mutant exhibiting increased avidity for agonist-bound GPCRs is expressed with
      B2R. Stabilizing receptor/beta-arrestin complexes into endosomes results in the
      dampening of the BK-mediated NO production. These results provide evidence for
      the involvement of beta-arrestin in the intracellular trafficking of B2R, and
      highlight the importance of receptor recycling in reestablishing B2R signaling.

PMID- 15993750
TI  - The last five amino acid residues at the C-terminus of PRK1/PKN is essential for
      full lipid responsiveness.
AB  - PRK1/PKN is a member of the protein kinase C (PKC) superfamily of
      serine/threonine protein kinases. Despite its important role as a RhoA effector,
      limited information is available regarding how this kinase is regulated. We show
      here that the last seven amino acid residues at the C-terminus is dispensable for
      the catalytic activity of PRK1 but is critical for the in vivo stability of this
      kinase. Surprisingly, the intact hydrophobic motif in PRK1 is dispensable for 3
      phosphoinositide-dependent kinase-1 (PDK-1) binding and phosphorylation of the
      activation loop, as the PRK1-Delta940 mutant lacking the last two residues of the
      hydrophobic motif and the last 5 residues at the C-terminus interacts with PDK-1
      in vivo and has a similar specific activity as the wild-type protein. We also
      found that the last four amino acid residues at the C-terminus of PRK1 is
      critical for the full lipid responsiveness as the PRK1-Delta942 deletion mutant
      is no longer activated by arachidonic acid. Our data suggest that the very C
      terminus in PRK1 is critically involved in the control of the catalytic activity
      and activation by lipids. Since this very C-terminal segment is the least
      conserved among members of the PKC superfamily, it would be a promising target
      for isozyme-specific pharmaceutical interventions.

PMID- 15993751
TI  - Differential modulation of COX-2 expression in A549 airway epithelial cells by
      structurally distinct PPAR(gamma) agonists: evidence for disparate functional
      effects which are independent of NF-(kappa)B and PPAR(gamma).
AB  - Ligands of peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) are
      thought to possess anti-inflammatory properties mediated via both PPAR(gamma)
      dependent and independent mechanisms. This work investigates the effects of
      PPAR(gamma) ligands on the regulation of cyclooxygenase-2 (COX-2) in the human
      lung epithelial cell line, A549. The synthetic ligand troglitazone activated the
      phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase pathway
      (MAPK), whereas the endogenous ligand, 15-deoxy-Delta(12,14)-prostaglandin J2
      (15d-PGJ2), only activated the PI3K pathway. 15d-PGJ2 had no detectable effects
      on COX-2, mPGES expression, or PGE2 production. However, troglitazone induced
      time-dependent COX-2 expression, which was insensitive to PPAR(gamma)
      antagonists, but was abrogated by inhibitors of PI3K and the ERK MAP kinase
      pathway. Furthermore, troglitazone induced mPGES expression and PGE2 production.
      Neither troglitazone nor 15d-PGJ2 was able to convincingly activate NF-kappaB in
      A549 cells. Further heterogeneity in the responses to troglitazone and 15d-PGJ2
      was observed in the regulation of gene expression as assessed by microarray
      analysis. In summary, this study provides compelling evidence that troglitazone
      (like 15d-PGJ2) can exert functional effects independently of actions via
      PPAR(gamma). Moreover, we have identified unique biochemical and functional
      actions of troglitazone that are not shared by 15d-PGJ2, which may influence the
      therapeutic potential of this compound in inflammatory settings.

PMID- 15993753
TI  - Identification of an integral plasma membrane pool of protein kinase C in
      mammalian tissues and cells.
AB  - Protein kinase C (PKC) is a family of serine/threonine protein kinases that are
      pivotal in cellular regulation. Since its discovery in 1977, PKCs have been known
      as cytosolic and peripheral membrane proteins. However, there are reports that
      PKC can insert into phospholipids vesicles in vitro. Given the intimate
      relationship between the plasma membrane and the activation of PKC, it is
      important to determine whether such "membrane-inserted" form of PKC exists in
      mammalian cells or tissues. Here, we report the identification of an integral
      plasma membrane pool for all the 10 PKC isozymes in vivo by their ability to
      partition into the detergent-rich phase in Triton X-114 phase partitioning, and
      by their resistance to extractions with 0.2 M sodium carbonate (pH 11.5), 2 M
      urea and 2 M sodium chloride. The endogenous integral membrane pool of PKC in
      mouse fibroblasts is found to be acutely regulated by phorbol ester or
      diacylglycerol, suggesting that this pool of PKC may participate in cellular
      processes known to be regulated by PKC. At least for PKC(alpha), the C2-V3 region
      at the regulatory domain of the kinase is responsible for membrane integration.
      Further exploration of the function of this novel integral plasma membrane pool
      of PKC will not only shed new light on molecular mechanisms underlying its
      cellular functions but also provide new strategies for pharmaceutical modulation
      of this important group of kinases.

PMID- 15993752
TI  - Early immune response and regulation of IL-2 receptor subunits.
AB  - Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes
      and probe sets in activated T-cells; analysis revealed that 217 genes were
      significantly upregulated within 4 h. Induced genes included transcription
      factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR
      confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha). Forty
      eight of the 217 induced genes are known to or predicted to be regulated by a CRE
      promoter/enhancer. We found that T-cell activation caused a significant increase
      in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203
      reduced CREB activation by 50% and inhibition of the PKA pathway caused a total
      block of CREB phosphorylation and significantly reduced IFN(gamma), IL-2 and IL
      2R(alpha) gene expression by approximately 40% (p<0.001). PKC(theta) plays a
      major role in T-cell activation: inhibition of PKC significantly reduced the
      expression of IFN(gamma), IL-2 and IL-2R(alpha). Since PKC blocked activation of
      CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways,
      PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors.
      Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be
      significantly activated greater than seven-fold within 30 min; however, there was
      little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of
      the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2
      activation at all time points, inhibition of MEK1 and 2 significantly blocked
      expression of IL-2 and IL-2R(alpha). Gene expression of IL-2R(alpha) and
      IFN(gamma) was dependent on PKA in S49 wt cells but not in kin- mutants. Using
      gel shift analysis, we found that forskolin activation of T-cells resulted in
      activation of AP1 sites; this increase in nuclear extract AP1 was significantly
      blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the
      PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation
      and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

PMID- 15993754
TI  - PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and
      cell chemotaxis.
AB  - Serine/threonine p21-activated kinase is an effector of Rac with a key role in
      the regulation of cytoskeletal organization. Non-muscle myosin II is a molecular
      motor, which is an important component of the cytoskeleton. Non-muscle myosin II
      B plays a major role in cell motility and chemotaxis. We investigated the role of
      Rac and p21-activated kinase 1 (PAK1) in the regulation of myosin II-B in
      prostate cancer cells in response to epidermal growth factor (EGF) stimulation.
      We found that both Rac and PAK1 affect EGF-dependent non-muscle heavy chain II-B
      localization and cell morphology. We further found that a dominant negative
      mutant of PAK1 significantly inhibits EGF-dependent myosin II-B heavy chains
      phosphorylation and filament disassembly. Furthermore, cells expressing the
      dominant negative mutant exhibited an increase in EGF-dependent myosin light
      chain phosphorylation and diminished chemotaxis towards EGF. To our knowledge
      this is the first report exploring the role of PAK1 in the regulation of both non
      muscle myosin II-B heavy chains and light chains. Furthermore, the data presented
      here suggest that PAK1 plays a crucial role in the regulation of cell morphology
      and chemotaxis by regulating the phosphorylation and cellular localization of
      myosin II-B.

PMID- 15993755
TI  - Protein kinase C zeta associates with death inducing signaling complex and
      regulates Fas ligand-induced apoptosis.
AB  - Previous studies have shown that Protein kinase C (PKC) stimulation may interfere
      with Fas signaling pathway and Fas ligand (FasL)-induced apoptosis. In this
      study, we investigated in Jurkat cells, a FasL-sensitive human T-cell model,
      whether PKC(zeta) targets apical events of Fas signaling. We describe for the
      first time that in Jurkat cells, both PKC(zeta) and Prostate apoptosis response-4
      (Par-4), one of the major endogenous PKC(zeta) regulators, are components of the
      death inducing signaling complex (DISC). Using PKC(zeta) overexpressing cells or
      si-RNA depletion, we demonstrate that PKC(zeta) interferes neither with Fas
      expression nor Fas clustering in raft microdomains, but negatively regulates FasL
      induced apoptosis by interfering with DISC formation and subsequent caspase-8
      processing.

PMID- 15993756
TI  - The predictive value of the leveling off of within session performance for
      procedural memory consolidation.
AB  - In addition to performance gains accrued concurrently with a given training
      experience (within-session gains) robust, delayed (between-session) performance
      gains may slowly evolve in the absence of any additional practice in a variety of
      tasks. The latter is regarded as a behavioral manifestation of skill memory
      consolidation. It is not known, however, how much practice is necessary for the
      triggering of these consolidation effects. Here, using an enumeration task, we
      show that the triggering of delayed gains could be robustly predicted from each
      individual's performance curve. Delayed performance gains evolved consistently
      only when practice continued to the point at which within-session performance
      leveled off (saturation). No delayed gains were found when training was stopped
      before this individually determined point. Our results support the notion that
      the triggering of consolidation processes depends on the saturation of a
      distinct, early phase of learning rather than on the absolute number of task
      repetitions, and suggest the possibility that training and rehabilitation
      protocols could be optimized on an individual basis.

PMID- 15993757
TI  - EEG evidence for mirror neuron dysfunction in autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are largely characterized by deficits in
      imitation, pragmatic language, theory of mind, and empathy. Previous research has
      suggested that a dysfunctional mirror neuron system may explain the pathology
      observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over
      sensorimotor cortex are thought to reflect mirror neuron activity, one method for
      testing the integrity of this system is to measure mu responsiveness to actual
      and observed movement. It has been established that mu power is reduced (mu
      suppression) in typically developing individuals both when they perform actions
      and when they observe others performing actions, reflecting an
      observation/execution system which may play a critical role in the ability to
      understand and imitate others' behaviors. This study investigated whether
      individuals with ASD show a dysfunction in this system, given their behavioral
      impairments in understanding and responding appropriately to others' behaviors.
      Mu wave suppression was measured in ten high-functioning individuals with ASD and
      ten age- and gender-matched control subjects while watching videos of (1) a
      moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own
      hand. Control subjects showed significant mu suppression to both self and
      observed hand movement. The ASD group showed significant mu suppression to self
      performed hand movements but not to observed hand movements. These results
      support the hypothesis of a dysfunctional mirror neuron system in high
      functioning individuals with ASD.

PMID- 15993758
TI  - Impaired cognitive control and reduced cingulate activity during mental fatigue.
AB  - Neurocognitive mechanisms underlying the effects of mental fatigue are poorly
      understood. Here, we examined whether error-related brain activity, indexing
      performance monitoring by the anterior cingulate cortex (ACC), and strategic
      behavioural adjustments were modulated by mental fatigue, as induced by 2 h of
      continuous demanding cognitive task performance. Findings that (1) mental fatigue
      is associated with compromised performance monitoring and inadequate performance
      adjustments after errors, (2) monitoring functions of ACC and striatum rely on
      dopaminergic inputs from the midbrain, and (3) patients with striatal dopamine
      deficiencies show symptomatic mental fatigue, suggest that mental fatigue results
      from a failure to maintain adequate levels of dopaminergic transmission to the
      striatum and the ACC, resulting in impaired cognitive control.

PMID- 15993759
TI  - Cerebral asymmetry in children when reading Chinese characters.
AB  - This study examined cerebral asymmetry, especially in the hierarchical visual
      system, when reading Chinese characters. Twelve right-handed Chinese children
      (mean age = 11.6 years) were scanned while performing semantic and phonological
      tasks. Strong leftward asymmetry was found in the left inferior frontal cortex
      (BA44/45/47), the parietal lobule (BA40), and the cingulate cortex (BA24/32). In
      the visual system, we found significant left-hemispheric dominance in the
      fusiform cortex (BA19/37), but no asymmetry was found in the primary visual
      cortex (BA17/18). The differential results for the primary visual cortex versus
      high-order visual cortex (i.e., the fusiform cortex) are discussed in terms of
      the contribution of the logographic nature of Chinese characters to the asymmetry
      pattern in the hierarchical visual system.

PMID- 15993760
TI  - Stimulus sequence affects schizophrenia-normal differences in event processing
      during an auditory oddball task.
AB  - Schizophrenia patients have difficulty distinguishing relevant from irrelevant
      auditory information. Auditory oddball paradigms are commonly used to investigate
      the processing of stimulus relevance. The present study used dense-array EEG and
      distributed source reconstructions to examine schizophrenia-normal differences in
      the processing of targets and standards as a function of the temporal sequence of
      stimuli. Brain responses were evaluated separately for early and late standards
      (standards 1-3 and 4-6 following a target, respectively) and early and late
      targets (those following 2-3 standards and 4-6 standards, respectively). The
      latencies of peaks (N1, P2, P3) in the event-related potential (ERP) waveforms
      did not differ between schizophrenia and normal subjects. However, schizophrenia
      normal differences in neural activity, derived from minimum norm estimation,
      occurred at specific times during stimulus processing as a function of stimulus
      sequence. Schizophrenia patients displayed smaller activity than normals in early
      ERPs (left hemispheric N1, right frontal P2) to late targets, and they produced
      P3-like responses to late standards. Furthermore, during the P2/N2 time interval,
      opposite patterns of brain activity were elicited in schizophrenia and normal
      subjects in response to standards, indicating different neural responses to the
      same stimulus events. These results suggest attention allocation to task
      irrelevant stimuli in schizophrenia, consequent upon insufficient representation
      of stimulus significance and context. Thus, schizophrenia compromises the ability
      to properly use context to solve even simple cognitive problems.

PMID- 15993761
TI  - The relationship between local and global processing and the processing of high
      and low spatial frequencies studied by event-related potentials and source
      modeling.
AB  - The processing of global and local elements and of low- and high-spatial
      frequencies are thought to be interrelated. Evidence for this stems from findings
      showing that brain localizations for global/local elements and for low/high
      spatial frequencies seem to overlap. The present study aimed to provide direct
      evidence that topographical differences between the processing of global and
      local visual elements can directly be explained by their spatial frequency
      content, and to study at which point in time this relation is present. This was
      done by studying the event-related potentials (ERPs) and source models elicited
      by unfiltered, low- or high-pass filtered hierarchical stimuli. Results showed
      that performance for global and local targets was affected by removing low and
      high spatial frequencies, respectively. ERP data indicated that at 250 ms, there
      was an interaction between the processing of global/local targets and of spatial
      frequencies because at this time-point removal of low spatial frequencies
      decreased activity associated with the processing of global targets. When
      localizing this effect, we found evidence implying that spatial frequency content
      indeed affected the brain region in which local/global targets were processed.
      Results implicated that the processing of global information depended on its low
      spatial frequency content, which was processed more laterally. Instead,
      processing of local information seemed to depend on its high spatial frequency
      content, which was processed more medially. Thereby, present results extend
      former results showing that global and local processing is dependent on spatial
      frequency and mapped retinotopically in the visual cortex.

PMID- 15993762
TI  - Involvement of both prefrontal and inferior parietal cortex in dual-task
      performance.
AB  - This PET study explored the neural substrate of both dual-task management and
      integration task using single tasks that are known not to evoke any prefrontal
      activation. The paradigm included two simple (visual and auditory) discrimination
      tasks, a dual task and an integration task (requiring simultaneous visual and
      auditory discrimination), and baseline tasks (passive viewing and hearing). Data
      were analyzed using SPM99. As predicted, the comparison of each single task to
      the baseline task showed no activity in prefrontal areas. The comparison of the
      dual task to the single tasks demonstrated left-sided foci of activity in the
      frontal gyrus (BA 9/46, BA 10/47 and BA 6), inferior parietal gyrus (BA 40), and
      cerebellum. By reference to previous neuroimaging studies, BA 9/46 was associated
      with the coordinated manipulation of simultaneously presented information, BA
      10/47 with selection processes, BA 6 with articulatory rehearsal, and BA 40 with
      attentional shifting. Globally similar regions were found for the integration
      task, except that the inferior parietal gyrus was not recruited. These results
      confirm the hypothesis that the left prefrontal cortex is implicated in dual-task
      performance. Moreover, the involvement of a parietal area in the dual task is in
      keeping with the hypothesis that a parieto-frontal network sustains executive
      functioning.

PMID- 15993763
TI  - EEG alpha band dissociation with increasing task demands.
AB  - In assuming functional differences between different EEG alpha frequency bands,
      recent studies emphasize the importance of using narrow (8-10 Hz or 10-12 Hz)
      instead of broad alpha frequency ranges (8-12 Hz). Due to individual differences
      in alpha activity, it has also been suggested to adjust alpha frequency bands
      individually for each participant. The present paper highlights the dissociating
      role of different task demands on the extent of event-related desynchronization
      (ERD) in different alpha frequency bands. In analyzing the data of four large
      scale EEG studies (with sample sizes of 51, 58, 55, and 66, respectively)
      employing a wide range of cognitive tasks, we found evidence that the
      correlations between lower and upper alpha band ERD systematically decline as
      task demands increase.

PMID- 15993764
TI  - Category-related brain activity to natural categories is associated with the
      retrieval of visual features: Evidence from repetition effects during visual and
      functional judgments.
AB  - It is debated whether category-related brain activation reflects a modality
      specific (e.g., visual, functional representation systems) or a domain-specific
      (e.g., natural vs. artifactual categories) semantic memory organization. The
      present event-related potentials (ERPs) study is aimed at elucidating the nature
      of semantic representations of objects from natural (e.g., animal) and
      artifactual (e.g., tool) categories. Within a repetition priming paradigm, we
      tested the assumption that modality-specific semantic systems are differentially
      involved in representing artifacts and natural kinds by probing either visual or
      functional knowledge in a test task. In the exposure phase, subjects performed a
      classification task on object names for artifacts and natural objects. In the
      test phase, these previously presented (old) names were presented together with
      new names, and subjects had to perform either a visual (shape) or a functional
      (use) judgment. As in previous ERP studies, words from natural categories were
      associated with a more positive potential at occipito-parietal electrodes than
      words from artifactual categories. This effect was only obtained during the
      visual judgment task. This category-related ERP effect was diminished for words
      that had been previously presented. In the functional judgment task, category
      related ERP effects were not obtained at all, probably due to the heterogeneity
      of the probed features. The observed interaction between task, category and
      repetition provides direct evidence that visual features play a more important
      role for the representations of natural compared to artifactual categories. Our
      data are therefore compatible with the notion of modality-specific semantic
      systems.

PMID- 15993765
TI  - Processing of Japanese morphogram and syllabogram in the left basal temporal
      area: electrical cortical stimulation studies.
AB  - Language functions in the left basal temporal area (LBTA) were investigated using
      electrical cortical stimulation during functional mapping in six Japanese
      patients with refractory epilepsy. This study provides the first direct evidence
      that kana (Japanese syllabogram) is processed in the LBTA. Electrical stimulation
      of some areas within LBTA induced disturbance in overt reading of kana words only
      in the first trials, with no errors in the subsequent trials. By contrast,
      stimulation of the same area caused obvious disturbance in kana non-word reading
      in all trials. Since a kana word carries both meaning and sound while a kana non
      word carries only sounds of a letter string, the contrasting results of partial
      and complete disturbance imply a possibility that there are two distinct pathways
      for kana reading: one dealing with both phonological and semantic aspects of the
      words and the other dealing only with phonological aspect. Kanji words (Japanese
      morphogram) and objects/pictures were found to be processed in an area different
      from the area for the kana non-word processing. Furthermore, the present study
      also identified the common area for processing kanji reading and object/picture
      naming. There were no errors in matching pictures with kanji words, indicating
      that concepts of pictures and meanings of kanji words were not interfered by the
      electrical stimulation of that area. The new insight provides a clue for partial
      description of processing pathways for language-related visual information in
      LBTA. Three types of information (morphological, phonological, and semantic) are
      conveyed together at some stages and are separated into different routes at some
      other stages.

PMID- 15993766
TI  - Task-independent semantic activation for numbers and animals.
AB  - Semantic processing of numbers and animals was contrasted with PET in two
      different tasks (comparison and classification) to test the hypothesis that
      knowledge about numbers is associated with increased activation in the parietal
      cortices, regardless of the semantic task (i.e. CLASSIFICATION: is seven odd?
      Comparison: is seven larger than 5?). By contrast, processing animal names was
      expected to produce activation in inferior temporal areas. Task-independent
      activation was observed in the left and right intraparietal sulci for number
      names, whereas task-independent activation of the left inferior temporal gyrus
      was found for animal names. No significant interaction between the category
      (numbers or animals) and the semantic task (comparison or classification) was
      observed. Accordingly, the IPS activation classically observed during numerical
      processing appears to be related to category-specific semantic knowledge about
      numbers. Likewise, the activation of the inferior temporal gyrus associated with
      the processing of animal names is probably related to category-specific knowledge
      about animals. The results strongly support the hypothesis that different brain
      regions are important for storing conceptual knowledge about different semantic
      categories.

PMID- 15993767
TI  - Distinct fMRI responses to laughter, speech, and sounds along the human peri
      sylvian cortex.
AB  - In this event-related fMRI study, 12 right-handed volunteers heard human
      laughter, sentential speech, and nonvocal sounds in which global temporal and
      harmonic information were varied whilst they were performing a simple auditory
      target detection. This study aimed to delineate distinct peri-auditory regions
      which preferentially respond to laughter, speech, and nonvocal sounds. Results
      show that all three types of stimuli evoked blood-oxygen-level-dependent
      responses along the left and right peri-sylvian cortex. However, we observed
      differences in regional strength and lateralization in that (i) hearing human
      laughter preferentially involves auditory and somatosensory fields primarily in
      the right hemisphere, (ii) hearing spoken sentences activates left anterior and
      posterior lateral temporal regions, (iii) hearing nonvocal sounds recruits
      bilateral areas in the medial portion of Heschl's gyrus and at the medial wall of
      the posterior Sylvian Fissure (planum parietale and parietal operculum).
      Generally, the data imply a differential regional sensitivity of peri-sylvian
      areas to different auditory stimuli with the left hemisphere responding more
      strongly to speech and with the right hemisphere being more amenable to nonspeech
      stimuli. Interestingly, passive perception of human laughter activates brain
      regions which control motor (larynx) functions. This observation may speak to the
      issue of a dense intertwining of expressive and receptive mechanisms in the
      auditory domain. Furthermore, the present study provides evidence for a
      functional role of inferior parietal areas in auditory processing. Finally, a
      post hoc conjunction analysis meant to reveal the neural substrates of human
      vocal timbre demonstrates a particular preference of left and right lateral parts
      of the superior temporal lobes for stimuli which are made up of human voices
      relative to nonvocal sounds.

PMID- 15993768
TI  - Effects of dynamic rotation on event-related brain potentials.
AB  - Event-related potentials were recorded during a mental rotation task. Subjects
      were shown pairs of letter-like shapes and were asked to make a parity judgment.
      The shape on the left was always in its canonical position and the shape on the
      right could either be in its canonical position or be a mirror image. Two
      variables were manipulated for the shape on the right. First, it could appear at
      different orientations (50 degrees , 100 degrees or 150 degrees ); second, it
      could be presented in a stationary position, in a dynamic congruent direction
      (the shape slowly rotating toward its normal upright position) or in a dynamic
      incongruent direction (the shape slowly rotating in the opposite direction to its
      normal upright position). Orientation- and direction-dependent modulations of a
      negative slow wave were found. For orientation, the typical amplitude effect over
      parietal sites was found, the amplitude becoming more negative as the rotational
      angle increased. For direction, the amplitude of the negative slow wave was
      larger for stationary and dynamic incongruent trials than for dynamic congruent
      trials at 100 degrees and 150 degrees . This result suggests that presentation of
      a stimulus in a dynamic congruent direction facilitates the mental rotation
      process. At 50 degrees , differences between dynamic incongruent trials and both
      stationary and dynamic congruent trials were found, suggesting that the
      incongruent movement elicits an obstructing effect over the mental rotation
      process. In summary, the present experiment provides new evidence in support of
      the idea that the amplitude modulation over the parietal cortex is a
      psychophysiological marker of the mental rotation process.

PMID- 15993769
TI  - Error processing and impulsiveness in normals: evidence from event-related
      potentials.
AB  - Electrophysiological correlates of impulsiveness were investigated in thirty-two
      healthy subjects using event-related potentials (ERP). Impulsiveness was
      determined by calculating individual reaction times (as a function of general
      response speed) in order to split the entire group into two subgroups with a more
      controlled (n = 16) and less controlled (n = 16) response style. Participants
      performed a Go/Nogo task while a 64 channel EEG was recorded. Artifact-free EEG
      segments were used to compute ERPs on correct Go trials and incorrect Nogo
      trials, separately. Three ERP components were of special interest: the error
      related negativity (ERN)/error negativity (Ne) and the "early" error positivity
      (Pe) reflecting automatic error processing and the "late" error positivity (Pe)
      which is thought to mirror the awareness of erroneous responses. Subjects with
      higher impulsiveness showed smaller amplitudes than subjects with lower
      impulsiveness for the ERN/Ne component and the "early" Pe component. With regard
      to the "late" Pe groups did not differ. Hence, ERP measures appear suitable for
      detailed analyses of impulsiveness in healthy participants. Moreover, present
      results argue for the necessity of careful control of impulsiveness when
      including normal comparison groups in the context of clinical studies.

PMID- 15993770
TI  - The role of multisensory memories in unisensory object discrimination.
AB  - Past multisensory experiences can influence current unisensory processing and
      memory performance. Repeated images are better discriminated if initially
      presented as auditory-visual pairs, rather than only visually. An experience's
      context thus plays a role in how well repetitions of certain aspects are later
      recognized. Here, we investigated factors during the initial multisensory
      experience that are essential for generating improved memory performance.
      Subjects discriminated repeated versus initial image presentations intermixed
      within a continuous recognition task. Half of initial presentations were
      multisensory, and all repetitions were only visual. Experiment 1 examined whether
      purely episodic multisensory information suffices for enhancing later
      discrimination performance by pairing visual objects with either tones or
      vibrations. We could therefore also assess whether effects can be elicited with
      different sensory pairings. Experiment 2 examined semantic context by
      manipulating the congruence between auditory and visual object stimuli within
      blocks of trials. Relative to images only encountered visually, accuracy in
      discriminating image repetitions was significantly impaired by auditory-visual,
      yet unaffected by somatosensory-visual multisensory memory traces. By contrast,
      this accuracy was selectively enhanced for visual stimuli with semantically
      congruent multisensory pasts and unchanged for those with semantically
      incongruent multisensory pasts. The collective results reveal opposing effects of
      purely episodic versus semantic information from auditory-visual multisensory
      events. Nonetheless, both types of multisensory memory traces are accessible for
      processing incoming stimuli and indeed result in distinct visual object
      processing, leading to either impaired or enhanced performance relative to
      unisensory memory traces. We discuss these results as supporting a model of
      object-based multisensory interactions.

PMID- 15993771
TI  - Activity and functional connectivity of inferior frontal cortex associated with
      response conflict.
AB  - The traditional Stroop test of cognitive interference requires overt speech
      responses. One alternative, the counting Stroop, generates cognitive interference
      similar to the traditional Stroop test but allows button press responses.
      Previous counting Stroop studies have used concrete words in the control
      condition, which may have masked inferior frontal activation. We studied 7
      healthy young adults using fMRI on a counting Stroop condition, with a
      nonlinguistic control condition (geometric shapes). As expected, we found
      activation in bilateral inferior frontal gyri, as well as in lateral and medial
      prefrontal, inferior parietal, and extrastriate cortices. Additional functional
      connectivity analyses using inferior frontal activation clusters (right area 44,
      left area 47) as seed volumes showed connectivity with superior frontal area 8
      and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex
      was related to response conflict and inhibition. Connectivity with left
      perisylvian language areas was not observed, which further underscores the
      nonlinguistic nature of inferior frontal activity. We conclude that bilateral
      inferior frontal cortex is involved in response suppression associated with
      interference in the counting Stroop task.

PMID- 15993772
TI  - Auditory perceptual grouping and attention in dyslexia.
AB  - Despite dyslexia affecting a large number of people, the mechanisms underlying
      the disorder remain undetermined. There are numerous theories about the origins
      of dyslexia. Many of these relate dyslexia to low-level, sensory temporal
      processing deficits. Another group of theories attributes dyslexia to language
      specific impairments. Here, we show that dyslexics perform worse than controls on
      an auditory perceptual grouping task. The results show differences in performance
      between the groups that depend on sound frequency and not solely on parameters
      related to temporal processing. Performance on this task suggests that dyslexics'
      deficits may result from impaired attentional control mechanisms. Such deficits
      are neither modality nor language-specific and may help to reconcile differences
      between theories of dyslexia.

PMID- 15993773
TI  - Infection as a complication of neuraxial blockade.

PMID- 15993774
TI  - Epidural abscess in an obstetric patient with patient-controlled epidural
      analgesia--a case report.
AB  - We present the case of a 37-year-old pregnant woman who underwent a cesarean
      section due to previous cesarean delivery. Spinal anesthesia was performed at the
      L2-3 intervertebral space with an epidural catheter inserted at L1-2 for
      postoperative patient-controlled epidural analgesia. When the epidural catheter
      was removed on day three, an area of redness round the entry point was noted and
      the patient complained of low back pain, but was discharged from hospital. Later
      the same day, she felt backache so severe that she was unable to stand up or bend
      her body. She called for help and was sent to our emergency room. Physicians
      noted a small amount of discharge from the insertion site, and the body
      temperature was elevated to 38 degrees C. An anesthesiologist and an infectious
      disease specialist were consulted, and an epidural abscess was suspected. Urgent
      magnetic resonance imaging revealed an epidural abscess at L1-2. After five days
      of unsuccessful treatment with oxacillin, a 28-day course of vancomycin, followed
      by two months of oral fusidic acid, resulted in complete remission of the
      epidural abscess. The patient has remained free of neurologic deficit.

PMID- 15993775
TI  - The disappearing art of obstetric general anaesthesia in the UK: implications for
      overseas trainees.

PMID- 15993776
TI  - The emergence of genomic and proteomic biomarkers in heart transplantation.

PMID- 15993777
TI  - Nodular endocardial infiltrates (Quilty lesions) cause significant variability in
      diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients.
AB  - BACKGROUND: Endomyocardial biopsy is used to guide therapy after heart
      transplantation. An accurate and reliable diagnosis of rejection is critical for
      proper patient management. METHODS: A sub-set of 827 biopsies from 273 patients
      were identified from 8 centers participating in the Cardiac Allograft Gene
      Expression Observational Study. These included all biopsies graded by local
      center pathologists as International Society for Heart and Lung Transplantation
      (ISHLT) Grade 1B or higher and also randomly chosen Grade 0 and 1A biopsies. Each
      of these cases was reviewed in a blinded manner by 3 study pathologists in the
      absence of clinical data. The study pathologists were assigned an ISHLT grade and
      noted nodular endocardial infiltrates (Quilty lesions). RESULTS: The study
      pathologists were significantly more likely than local pathologists to diagnose
      ISHLT Grade 0, 1A and 3B rejection and significantly less likely to diagnose
      ISHLT Grade 1B, 2 and 3A rejection. Concordance between local and study
      pathologists was lowest for Grade 2 (17% agreement). Quilty lesions were noted in
      3.3% of local Grade 0 cases and in 31% and 37% of local Grade 2 and 3A cases,
      respectively. Quilty lesions were recognized by study pathologists in 35% of
      local Grade 2 cases "downgraded" to Grade 0 or 1, but in only 10% of local Grade
      2 cases confirmed by study pathologists. CONCLUSIONS: The greatest variability
      between pathologists in application of the ISHLT grading system is in Grade 2
      biopsies, and Quilty lesions are a major contributing factor to the lack of
      concordance. Accurate application of the ISHLT grading system requires improved
      recognition and understanding of Quilty lesions.

PMID- 15993778
TI  - Tricuspid regurgitation after cardiac transplantation: how many biopsies are too
      many?
AB  - BACKGROUND: Tricuspid regurgitation (TR) is common in patients after orthotopic
      cardiac transplantation (OHT). Endomyocardial biopsy (EMB) used to monitor for
      rejection may be a cause of TR. The purpose of this study was to identify a
      correlation between the severity of TR and the number of EMBs. METHODS: We
      studied 101 patients with OHT at our institution between May 1987 and August
      2001. The number of EMBs performed in each patient was determined. Data on
      technique of anastomosis, liver and renal function, ejection fraction, and
      pulmonary artery pressure were also extracted. Echocardiography reports were
      reviewed to determine the presence and severity of TR. Symptoms of right heart
      failure were assessed by the amount of diuretic intake. RESULTS: Twenty-five
      (25%) of 101 patients had evidence of severe TR, whereas 76 (75%) had non-severe
      TR. Multivariate analysis identified EMB as the only independent predictor of the
      severity of TR (p < 0.0001). At last follow-up, 60% of patients with more than 31
      EMBs had developed severe TR, whereas none of the patients with less than 18 EMBs
      had severe TR. Of the 25 patients who had severe TR, 15 (61%) needed high doses
      of daily diuretics, and 4 (16%) required tricuspid valve replacement.
      CONCLUSIONS: The development of TR after OHT is in large part due to EMBs used to
      monitor for rejection. There is a direct correlation between the number of EMBs
      and the severity of TR. We suggest a cutoff of less than 31 EMBs to reduce the
      risk of severe TR.

PMID- 15993779
TI  - Inhibition of obliterative airway disease development following heterotopic
      murine tracheal transplantation by costimulatory molecule blockade using anti
      CD40 ligand alone or in combination with donor bone marrow.
AB  - INTRODUCTION: Obliterative airway disease (OAD) development in heterotopic murine
      tracheal allografts, a model of obliterative bronchiolitis after lung
      transplantation, is immunologically mediated. Whether tolerance induction by the
      administration of anti-CD40 ligand monoclonal anti-body (MR-1) alone or in
      conjunction with donor-derived bone marrow cells (BMCs) can prevent the
      development of OAD was tested in this study. METHODS: BALB/c tracheal allografts
      were heterotopically transplanted into C57BL/6 recipients. Group 1 received no
      treatment. Group 2 received multiple infusions of donor BMCs intravenously. Group
      3 was administered MR-1 intraperitoneally. Group 4 received donor BMCs and MR-1.
      Allografts were harvested at several time points post-transplantation and
      examined for the development of OAD. RESULTS: Group 1 developed cellular
      infiltration and epithelial damage by Day 15 post-transplant and OAD by Day 28,
      evidenced by complete obliteration of the tracheal lumen. Group 2 developed OAD
      with similar kinetics to Group 1. Group 3 had no evidence of OAD at 28 days. At
      Days 45 to 90, moderate cellular infiltration, epithelial metaplasia, and a
      minimal narrowing of the tracheal lumen were evident. OAD developed by Day 120.
      Group 4 mice had patent tracheal lumens even at 120 days post-transplantation,
      with only mild epithelial metaplasia and luminal narrowing noted. CONCLUSIONS:
      The administration of MR-1 alone in combination with infusions of donor bone
      marrow cells significantly attenuated the development of OAD. Tolerance-inducing
      regimens such as this deserve further investigation in the prevention of post
      lung transplant obliterative bronchiolitis following human lung transplantation.

PMID- 15993780
TI  - Non-invasive detection of acute allograft rejection in children by tissue Doppler
      imaging: myocardial velocities and myocardial acceleration during isovolumic
      contraction.
AB  - BACKGROUND: In adults, an acute decrease of regional myocardial velocities is a
      sensitive marker of rejection. In children, velocities are more variable. A new
      marker, myocardial acceleration during isovolumic contraction (IVA), appears to
      be less age-dependent than myocardial velocities. This study therefore compared
      tissue Doppler (TDI)-derived velocities and IVA as potential rejection markers
      for children. METHODS: TDI was performed in 15 pediatric heart transplant
      recipients (age 8.0 +/- 3.6 years) during acute rejection and at baseline without
      rejection, 50 additional transplant children without rejection (7.8 +/- 5.9
      years) and 30 age-matched healthy children (7.5 +/- 5.2 years). Color Doppler
      cine-loops of 3 cardiac cycles were stored as echocardiographic raw data. Using
      off-line post-processing, systolic (S) and diastolic (E) myocardial velocities
      and IVA were measured in 5 basal left ventricular segments. IVA is the peak
      isovolumic contraction wave velocity divided by acceleration time. RESULTS:
      Without rejection, transplant children had significantly lower diastolic
      velocities (basal lateral E 10.4 +/- 2.9 vs 11.9 +/- 2.6 cm/s; p < 0.001) and
      systolic velocities (S 5.6 +/- 1.4 vs 7.1 +/- 2.0 cm/s; p < 0.001) than normal
      age-matched controls, but IVA was similar (1.2 +/- 1.4 vs 1.3 +/- 0.5 m/s2).
      During rejection, all markers decreased significantly compared with age-matched
      normal control, the non-rejecting transplant group and individual baseline
      values. CONCLUSIONS: Regional myocardial velocities change significantly during
      acute allograft rejection in children. However, many children already have wall
      motion abnormalities at baseline, so results are often difficult to interpret. In
      contrast, isovolumic acceleration was normal without rejection and selectively
      decreased during the event. IVA is a promising non-invasive rejection marker for
      pediatric patients.

PMID- 15993781
TI  - Pre-transplant panel reactive antibody in lung transplant recipients is
      associated with significantly worse post-transplant survival in a multicenter
      study.
AB  - BACKGROUND: The presence of antibodies to human leukocyte antigens (HLA) prior to
      transplantation has been linked to worse post-transplant outcomes in many solid
      organ transplants. The effect of these antibodies is less clear in lung
      transplant recipients, although previous studies have suggested an increased
      incidence of allograft dysfunction. METHODS: A retrospective study of all first
      lung transplant recipients from the University of Toronto (November 1983-July
      2001, n = 380) and Duke University (April 1992-June 2000, n = 276) was performed.
      Demographic data, survival information, and level of last pre-transplant panel
      reactive antibody (PRA) were collected. PRA level was measured by the complement
      dependent cell cytotoxicity assay at both centers. Survival analysis was
      performed using the Kaplan-Meier method, and groups were compared with the
      Wilcoxon rank sum test. RESULTS: Of 656 lung transplant recipients, 101 (15.4%)
      had a PRA greater than 0, 37 (5.6%) had a PRA greater than 10%, and 20 (3.0%) had
      a PRA greater than 25%. Patients with a PRA greater than 25% had decreased median
      survival than did the rest of the patients (1.5 vs 5.2 years) and at 1 month (70%
      vs 90%), 1 year (65% vs 76%), and 5 years (31% vs 50%), respectively (p = 0.006,
      Wilcoxon's rank sum test) test). CONCLUSION: Significant elevation of PRA prior
      to lung transplantation is associated with worse survival, especially in the
      early post-transplant period. This may be due to a direct effect of anti-HLA
      antibodies on the allograft. The effectiveness of treatments such as
      plasmapheresis and intravenous immunoglobulin prior to transplantation needs to
      be evaluated.

PMID- 15993782
TI  - Blood transfusions decrease the incidence of acute rejection in cardiac allograft
      recipients.
AB  - BACKGROUND: Cardiac transplant recipients frequently receive a large number of
      transfusions. The objective of this study was to determine whether there is an
      association between total number of blood transfusions and cardiac allograft
      rejection. METHODS: A retrospective analysis of all cardiac transplants between
      October 1, 1997, and December 31, 2001, was performed. Total number of
      transfusions, total number of rejection episodes Grade 3A or more, rejection-free
      survival, and overall survival were analyzed. Comparisons between patients
      bridged to transplantation with a Novacor left ventricular assist device (LVAD)
      and the primary transplant group were also made. RESULTS: Eighty-two patients
      were transplanted. Fifteen were bridged to transplantation, and 67 underwent
      primary heart transplantation. Age and sex were similar for the LVAD group and
      the primary transplant group (45 +/- 11 vs 47 +/- 15 years and 67% vs 58% male
      sex, respectively). Mean follow-up was 658 +/- 486 days for the LVAD group and
      708 +/- 548 days for the primary transplant group. Transfusions received were 50
      +/- 34 U of packed red blood cells for the LVAD group and 7 +/- 12 for the
      primary transplant group (p < 0.001). There were no differences in donor
      characteristics between the 2 groups. The incidence of acute rejection within 1
      year was 27% for the LVAD group and 39% for the primary transplant group (p =
      .28). Freedom from rejection was 71% at 1 year in the LVAD group compared with
      59% for the primary transplant group (p = 0.39). In all 82 patients, the total
      number of transfusions was inversely correlated with the development of acute
      rejection (p = 0.011). Survival was 80% and 62% for the LVAD group at 1 and 3
      years after transplantation and 88% and 85%, respectively, for the primary
      transplant group (p = 0.045). CONCLUSIONS: The number of blood transfusions
      received by heart transplant recipients is inversely related with the number of
      acute rejection episodes.

PMID- 15993784
TI  - Defining the full costs of endemic porcine proliferative enteropathy.

PMID- 15993785
TI  - Nutrition, behaviour and the role of supplements for calming horses: the
      veterinarian's dilemma.

PMID- 15993786
TI  - Equine herpesviruses 1 (EHV-1) and 4 (EHV-4)--epidemiology, disease and
      immunoprophylaxis: a brief review.
AB  - This review concentrates on the epidemiology, latency and pathogenesis of, and
      the approaches taken to control infection of horses by equine herpesvirus types 1
      (EHV-1) and 4 (EHV-4). Although both viruses may cause febrile rhinopneumonitis,
      EHV-1 is the main cause of abortions, paresis and neonatal foal deaths. The
      lesion central to these three conditions is necrotising vasculitis and thrombosis
      resulting from lytic infection of endothelial cells lining blood capillaries. The
      initiation of infection in these lesions is likely to be by reactivated EHV-1
      from latently infected leukocytes. However, host factors responsible for
      reactivation remain poorly understood. While vaccine development against these
      important viruses of equines involving classical and modern approaches has been
      ongoing for over five decades, progress, compared to other alpha herpesviruses of
      veterinary importance affecting cattle and pigs, has been slow. However recent
      data with a live temperature sensitive EHV-1 vaccine show promise.

PMID- 15993787
TI  - Calmatives for the excitable horse: a review of L-tryptophan.
AB  - Preparations that contain tryptophan are marketed world wide as calmative agents
      to treat excitable horses. Tryptophan is the amino acid precursor for serotonin,
      a neurotransmitter implicated in sedation, inhibition of aggression, fear and
      stress, in various animal species and humans. Experiments have shown that
      tryptophan supplementation decreases aggression in humans, dogs, pigs, poultry,
      and fish, and that it may reduce fearfulness and stress in calves, vixens and
      poultry. However, behavioural characteristics more closely linked to excitement,
      such as hyperactivity in dogs, are not modified by tryptophan supplementation.
      Research using a variety of animals other than horses, has shown that the
      behavioural response to tryptophan supplementation varies with age, breed and
      gender, and can be modified by diet, exercise, social status, and level of
      arousal. Significantly, the response is species-dependent, and there are no
      scientific publications that confirm the efficacy of tryptophan as a calmative in
      excitable horses. The few studies where tryptophan has been administered to
      horses suggest that low doses (relative to those contained in commercial
      preparations) cause mild excitement, whereas high doses reduce endurance
      capacity, and cause acute haemolytic anaemia if given orally, due to a toxic
      hindgut metabolite. As tryptophan continues to be used as an equine calmative,
      there is an urgent need for research to confirm its efficacy in horses, and to
      establish a safe therapeutic dose range. In the meantime, available data suggest
      that it would be imprudent to rely on tryptophan to calm the excitable horse, and
      instead, that a greater effort should be made to identify the underlying causes
      of excitability, and to explore more appropriate non-pharmacological remedies.

PMID- 15993788
TI  - Recent advances in equine abdominal surgery.
AB  - Laparoscopy is a minimally invasive procedure that has applications as a
      diagnostic, therapeutic and prognostic technique. Specialized equipment is
      necessary to perform equine laparoscopy, and there is a large range of
      instruments, both disposable and non-disposable available. Laparoscopic
      procedures described include ovariectomy, cryptorchidectomy, adhesiolysis and
      herniorrhaphy. Laparoscopy can be performed in a standing or dorsally recumbent
      position, depending on surgeon preference, patient status and the procedure to be
      performed. Stapling equipment is frequently used in gastrointestinal surgery in
      horses. Advantages include decreased surgical time and a decrease in the risk of
      contamination. Stapling equipment is often used in creating anastomoses, both in
      the large and small intestines, as well as in vessel ligation. New surgical
      techniques intended to decrease adhesion formation include the use of
      carboxymethylcellulose and bioresorbable patches. Indwelling abdominal drains can
      be used for peritoneal lavage following surgery and also appear to decrease the
      risk of adhesion formation. Improvements in post-operative care, including the
      treatment of post-operative ileus and endotoxaemia can significantly improve the
      outcome of horses that have undergone surgery for abdominal disorders.
      Recommendations for the use of prokinetic agents in horses with ileus vary
      widely. Prokinetic agents include local anaesthetics, macrolide antimicrobials,
      cholinergic agonists and dopamine antagonists. Endotoxaemia is common in horses
      following surgery for gastrointestinal disorders. The antibiotic polymyxin B
      binds to the circulating endotoxin molecule, decreasing its half-life in the
      intra-vascular space and reducing associated inflammation. This drug appears to
      be an effective and affordable treatment option for horses with endotoxaemia. The
      use of specific cyclooxygenase inhibitors in veterinary medicine have been
      studied recently. Selective cyclooxygenase-2 inhibitors may provide comparable
      anti-inflammatory and analgesic properties to the non-selective non-steroidal
      anti-inflammatory drugs. These drugs appear to have similar clinical
      effectiveness and will hopefully minimize deleterious side effects. The optimal
      healing of ventral midline incisions in horses is related to many factors
      including appropriate suture patterns and bite size, in addition to appropriate
      post-operative exercise recommendations. Recent advances in surgical techniques
      and post-operative care should decrease the morbidity and mortality associated
      with abdominal surgery. This article provides an overview of some of these
      advances.

PMID- 15993789
TI  - Apoptosis in the mammalian CNS: Lessons from animal models.
AB  - It is generally assumed that about half of the neurons produced during
      neurogenesis die before completion of maturation of the central nervous system
      (CNS). Neural cell death is also relevant in aging and several neurodegenerative
      diseases. Among the modalities by which neurons die, apoptosis has very much
      attracted the interest of investigators because in this type of cell death
      neurons are actively responsible for their own demise by switching on a number of
      genes and activating a series of specific intracellular pathways. This review
      focuses on the cellular and molecular mechanisms of apoptosis in normal and
      transgenic animal models related to naturally occurring neuronal death within the
      CNS. We will also consider some examples of apoptotic cell death in canine
      neuropathologies. A thorough analysis of naturally occurring neuronal death in
      vivo will offer a basis for parallel and future studies involving secondary
      neuronal loss such as those in neurodegenerative disorders, trauma or ischaemia.

PMID- 15993790
TI  - Thoracolaryngeal reflex latencies in Thoroughbred horses with recurrent laryngeal
      neuropathy.
AB  - Electrolaryngeography was used to study the latencies of the thoracolaryngeal
      adductor reflex in Thoroughbred horses with and without recurrent laryngeal
      neuropathy (RLN). Latencies were compared in horses with grades 1 and 2 RLN,
      diagnosed by endoscopy in resting horses. The reliability of the measurements,
      effect of sedation and correlations of latencies with age of the horse were also
      studied. There was no effect of sedation on reflex latency periods. The latency
      of the reflex period measured to a convolved peak of the electromyographic
      response was significantly different in horses with grades 1 and 2 disease;
      medians and quartile ranges were 0.067 (0.065-0.073) and 0.072 (0.068-0.074) s,
      respectively (P<0.05). Significant associations were found between reflex
      latencies and both horse age and the grade of RLN. Reflex latency measurements
      are reliable and sensitive, and may assist with the clinical appraisal of
      Thoroughbred horses with RLN.

PMID- 15993791
TI  - Surgery alone versus surgery and doxorubicin for the treatment of feline
      injection-site sarcomas: a report on 69 cases.
AB  - Sixty-nine cats were treated for injection-site sarcomas at the Veterinary
      Teaching Hospital of Grugliasco, Turin (Italy). The animals were divided into two
      subgroups: those subjected to four doxorubicin cycles combined with radical
      surgical excision 10 days after the second chemotherapy cycle (group A, 49 cats)
      or those treated with surgery alone (group B, 20 cats). Each cat was monitored
      for lung metastasis and local recurrence. In group A, 28 cats were alive at the
      end of the follow-up period. In this group, the recurrence rate was 40.8% while
      lung metastasis occurred in 12% of cats. In group B, eight animals were alive at
      the end of the follow-up period, while the rates of recurrence and metastasis
      were 35% and 10%. Neither the median disease-free interval nor the median overall
      survival was reached in either group. Moreover, there were no statistically
      significant differences between the two groups.

PMID- 15993792
TI  - The response of pigs to being loaded or unloaded onto commercial animal
      transporters using three systems.
AB  - Groups of pigs were subjected to three different systems of loading and unloading
      to and from commercial animal transporters. The systems under trial were: the use
      of a hydraulic tail-lift, a tail board ramp at an angle of 18 degrees and a
      modular system. The module was a container 2 m x 2.4 m x 1 m high into which the
      pigs were loaded. The module could then be lifted on and off the lorry with a
      fork lift truck. Non-invasive monitoring techniques were used to study the
      responses of the pigs. A subjective handling score, time taken to load and
      unload, skin temperature, heart rate and salivary cortisol were recorded. Loading
      and unloading were subjectively assessed as being easiest and quickest using the
      modular system, which also appeared to be less physically demanding for the
      animals, as evidenced by lower heart rate and a reduced maximum heart rate.
      However, with the modular system, elevated cortisol was found during the loading,
      unloading and resting periods. This could be interpreted as indicating that the
      pigs were unable to settle in the module and suffered some small degree of
      stress, which might become more of a problem during prolonged transport. Of the
      other two systems, there appeared to be little difference between the hydraulic
      tail-lift and the ramp.

PMID- 15993793
TI  - Pharmacodynamics and pharmacokinetics of flumequine in pigs after single
      intravenous and intramuscular administration.
AB  - The pharmacokinetics and intramuscular (IM) bioavailability of flumequine (15
      mgkg(-1)) were investigated in healthy pigs and the findings related to published
      minimal inhibitory concentrations (MICs) for susceptible bacteria of animal
      origin, and to experimentally determined MICs for susceptible strains of porcine
      origin. We found MICs for Escherichia coli, Salmonella spp., Pasteurella spp. and
      Bordetella spp. in the range 0.5 to >64 microg mL(-1) isolated from infected pigs
      in the Forli area of Italy; only the Pasteurella multocida strains were sensitive
      (MIC(90)=0.5 microg mL(-1)). After intravenous (IV) injection, flumequine was
      slowly distributed and eliminated (t(1/2lambda(1))1.40+/-0.16 h and
      t(1/2lambda(2))6.35+/-1.69 h). The distribution volume at steady state (V(dss))
      was 752.59+/-84.03 mL kg(-1) and clearance (Cl(B)) was 237.19+/-17.88 mL kg(-1)h(
      1). After IM administration, peak serum concentration (4.99+/-0.92 microg mL(-1))
      was reached between the 2nd and the 3rd hour. The results on MIC of isolated
      bacteria, although only indicative, suggest that the efficacy of flumequine on
      Gram-negative bacteria may be impaired by the emergence of less sensitive or
      resistant strains.

PMID- 15993794
TI  - Assessment of a platelet function analyser in horses: reference range and
      influence of a platelet aggregation inhibitor.
AB  - The objective of this study was to assess whether a new human platelet function
      analyser (the PFA-100) could be used to evaluate platelet function in horses and
      detect acetylsalicylic acid (ASA)-induced platelet dysfunctions. Citrated blood
      samples from 40 healthy horses were processed to obtain reference values for
      closure time (CT) using cartridges with collagen-ADP (CT-ADP) and collagen
      epinephrine (CT-EPI) as platelet agonists. In addition, CT-ADP and CT-EPI were
      also measured before and 24 h after oral ASA administration in another 12 healthy
      horses. The sensitivity and specificity of the test were also determined. In
      normal horses, means+/-SD value for CT-ADP was 85.1+/-13.1 s (median, 82 s), and
      CT-EPI ranged from 158 to >300 s (median 291 s). Calculated reference ranges were
      60.5-115.9 s and 158.5->300 s for CT-ADP and CT-EPI, respectively. Administration
      of ASA significantly (P<0.001) prolonged CT-ADP values from 91.0+/-13 to 113.5+/
      14.4 s, and CT-EPI values were also significantly (P<0.008) prolonged after ASA
      administration. Sensitivity and specificity results for ADP cartridges showed
      that a prolonged CT value would be highly suggestive of a platelet aggregation
      inhibition. In conclusion, ADP cartridges can be used in horses to assess primary
      haemostasis and may be a valuable test for the detection of platelet aggregation
      inhibition.

PMID- 15993795
TI  - Pharmaceutical and nutraceutical management of canine osteoarthritis: present and
      future perspectives.
AB  - Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases
      and causes of lameness in the dogs. The osteoarthritic disease process involves
      the entire synovial joint, encompassing the synovium, cartilage and underlying
      bone. Joint failure results from an abnormal mechanical strain causing damage to
      normal tissue or failure of pathologically impaired articular cartilage and bone
      under the influence of normal physiological strain or a combination of both. In
      both cases, the end point is cartilage loss and joint impairment. Osteoarthritic
      chondrocytes show an altered phenotype characterised by an excess production of
      catabolic factors, including metalloproteinases and reactive oxygen species.
      These factors constitute potential therapeutic targets and some new drugs and
      nutraceuticals have been proposed to promote the return to homeostasis. Until
      now, the therapeutic management of OA in dogs has been dominated by nonsteroidal
      anti-inflammatory drugs, but some new compounds, including diacerhein, with
      potential structure-modifying effects, are already used to treat OA in humans and
      could be helpful to manage OA in the dog. In addition, novel nutraceuticals, such
      as avocado/soybean unsaponifiable substances, have shown symptomatic effects in
      knee OA in humans, and could offer an alternative to prevent OA progression. This
      paper provides an overview of recent discoveries in the pathophysiology and in
      the therapeutic management of osteoarthritis in dogs.

PMID- 15993796
TI  - Transient complete atrioventricular block following transvenous electrical
      cardioversion of atrial fibrillation in a horse.
AB  - Transvenous electrical cardioversion was attempted in a horse with drug
      refractory atrial fibrillation. A temporary pacing catheter and two
      defibrillation catheters were inserted transvenously into the right ventricular
      apex, the right atrium and the pulmonary artery, respectively. Under general
      anaesthesia 100, 200, 300 and 360 J monophasic shocks were delivered between both
      defibrillation catheters but sinus rhythm could not be restored. Immediately
      after the 200, 300 and 360 J shock, transient third-degree atrioventricular block
      occurred for a period of, respectively, 15, 40 and 55 s. These periods of
      profound bradycardia were corrected by temporary right ventricular pacing until
      spontaneous conduction resumed. It is concluded that temporary right ventricular
      pacing should be available during electrical cardioversion of atrial fibrillation
      in horses.

PMID- 15993797
TI  - PMWS: an emerging disease identified in archived porcine tissues.
AB  - Postweaning multisystemic wasting syndrome (PMWS) is a disease caused by porcine
      circovirus type 2 (PCV-2). The disease was present as early as 1986 in Spain,
      1989 in Japan and 1993 in Thailand. In view of this, we considered it possible
      that the disease may also have been present in Switzerland prior to its first
      description in 2001. A retrospective investigation was performed on paraffin
      embedded lymphoid organs and ileum from 496 pigs aged 5-13 weeks collected
      between 1976 and mid-2001. The sections were investigated immunohistochemically
      using a monoclonal antibody specific for PCV-2 capsid antigen encoded by ORF2.
      Virus antigen was detected in tissue samples of 39 pigs from 28 farms. The
      earliest positive sample originated from 1986. After 1989, positive pigs were
      found almost every year among the 20-40 cases investigated annually. These
      results indicate that PCV-2 has been present in Switzerland for some time, and at
      least since 1986.

PMID- 15993798
TI  - Changes in malondialdehyde concentrations and glutathione peroxidase activity in
      purebred Arabian mares with endometritis.
AB  - Endometritis is an important factor in infertility. Free radicals play an
      important role in endometritis and we have investigated their possible role and
      scavenging systems in endometritis in purebred Arabian mares. The plasma
      concentration of malondialdehyde (MDA) and erythrocyte glutathione peroxidase
      (GPx) activity were compared in healthy mares and in mares with endometritis. The
      level of MDA was significantly increased while GPx activity was decreased in the
      mares with endometritis. Our findings support the notion that GPx is consumed by
      increased lipid peroxidation in purebred Arabian mares affected with
      endometritis.

PMID- 15993799
TI  - Effects of preoperative administration of meloxicam on whole blood platelet
      aggregation, buccal mucosal bleeding time, and haematological indices in dogs
      undergoing elective ovariohysterectomy.
AB  - The purpose of the study was to evaluate the effect of preoperative
      administration of meloxicam, a non-steroidal anti-inflammatory drug used for pain
      control, on primary haemostasis in dogs. Twenty healthy female dogs undergoing
      elective ovariohysterectomy were enrolled in the study. Sixty minutes before pre
      anaesthesia, a single dose of meloxicam (0.2 mg/kg) was randomly administered
      intravenously (IV) to 10 dogs (treatment group) while control dogs received an
      equivalent volume of saline solution IV. Platelet aggregation, buccal mucosa
      bleeding time, platelet count and haematological indices were measured at 0, 1, 6
      and 24 h after administration of meloxicam. Since significant differences between
      groups were not observed for any of the measured parameters, preoperative
      administration of meloxicam may be used for pain control before elective
      ovariohysterectomy in healthy dogs, without compromising primary haemostasis.

PMID- 15993801
TI  - Has the harassment act finally found its teeth in the battle against animal
      rights protestors?

PMID- 15993800
TI  - Common bile duct obstruction due to a duodenal gastrinoma in a dog.
AB  - In dogs gastrinomas are rare endocrine neoplasms that have always been reported
      to arise from the pancreas. We report here what we believe to be the first case
      of a duodenal gastrinoma in a dog. A nine-year-old, male, Pekinese dog was
      presented with a three-day history of anorexia, vomiting and mucous diarrhoea.
      Clinical examination and laboratory findings suggested the presence of a severe
      hepatobiliary disorder. Abdominal ultrasonography showed a diffuse increase in
      echogenicity of the liver, with severe gallbladder dilation and marked dilation
      of the cystic duct, common bile duct and extrahepatic bile ducts. Based on these
      findings, an extrahepatic biliary tract obstruction (EBTO) of unknown cause was
      suspected. At laparotomy, the gallbladder and the extrahepatic bile ducts
      appeared severely dilated. The gallbladder was tense and could not be compressed
      suggesting an outflow obstruction. The duodenum at the level of the common duct
      orifice appeared slightly thickened and severely hardened for a length of 1 cm.
      Biopsies from the duodenum and liver were obtained and a cholecystoduodenostomy
      was performed. The duodenal biopsy revealed severe fibrosis of the submucosa and
      a infiltrate of small pockets and cords of round to polygonal cells with granular
      cytoplasm. Based on this appearance the differential diagnoses included
      neuroendocrine tumours and poorly differentiated carcinoma. Despite surgery and
      supportive therapy the dog continued to be anorexic and to vomit 3-6 times daily.
      After euthanasia and necropsy, histopathology showed the presence of a
      neuroendocrine neoplasia involving the duodenal wall with focal invasion of the
      adjacent pancreas and small liver metastases. On immunohistochemistry, the
      cytoplasm of approximately 90% of neoplastic cells intensely expressed neuron
      specific enolase and gastrin. These findings were consistent with a diagnosis of
      gastrinoma.

PMID- 15993802
TI  - Neglected diseases: getting less neglected?

PMID- 15993803
TI  - Plethora of gut bugs promises personalization of drugs.

PMID- 15993804
TI  - Chemokine programming of T cell responses could offer new drug targets.

PMID- 15993805
TI  - Alice Huxley and Nick Miles of Speedel on the company's pipeline and future
      plans. Interview by Christopher Watson and Stephen Carney.

PMID- 15993806
TI  - Psoriasis: TNF-alpha inhibitors and beyond.

PMID- 15993807
TI  - Spot the dog, see Spot jump, watch spot denature.

PMID- 15993808
TI  - Improved early clinical development through human microdosing studies.

PMID- 15993809
TI  - Structural biology and drug discovery.
AB  - It has long been recognized that knowledge of the 3D structures of proteins has
      the potential to accelerate drug discovery, but recent developments in genome
      sequencing, robotics and bioinformatics have radically transformed the
      opportunities. Many new protein targets have been identified from genome analyses
      and studied by X-ray analysis or NMR spectroscopy. Structural biology has been
      instrumental in directing not only lead optimization and target identification,
      where it has well-established roles, but also lead discovery, now that high
      throughput methods of structure determination can provide powerful approaches to
      screening.

PMID- 15993810
TI  - Gastrointestinal patch systems for oral drug delivery.
AB  - Gastrointestinal patch systems with integrated multifunctions could surmount the
      challenges associated with conventional drug delivery. Several gastrointestinal
      patch systems provide bioadhesion, drug protection and unidirectional release.
      This combination of function could improve the overall oral bioavailability of
      large molecules that can currently be delivered only by injection, for example,
      epoetin-alpha and granulocyte-colony-stimulating factor, which are commonly used
      to treat chemotherapy-associated anemia and leukopenia, respectively.
      Furthermore, self-regulated release and cell-specific targeting provide
      additional 'smart' characteristics to this innovative therapeutic platform.

PMID- 15993811
TI  - Dopamine D3 receptor antagonists as therapeutic agents.
AB  - The behavioral and pathophysiological role of the dopamine D(3) receptor, which
      was deduced from anatomical, lesion and drug treatment studies in the ten years
      following cloning of the receptor, indicated that its functions differed from
      those of the D(2) receptor. There is increasingly strong evidence that D(3)
      receptor antagonists will be effective antipsychotic agents. In this regard, an
      amelioration of the negative and cognitive symptoms of schizophrenia holds the
      most promise for D(3) receptor antagonists, a concept currently under clinical
      evaluation. In addition, D(3) receptors could be involved in behavioral
      sensitization and the potential application of D(3) receptor antagonists in the
      treatment of drug abuse is undergoing intensive experimental investigation.

PMID- 15993812
TI  - Functional genomics in antibacterial drug discovery.
AB  - Antibacterial drug discovery has experienced a paradigm shift from phenotypic
      screening for antibacterial activity to rational inhibition of preselected
      targets. Functional genomics techniques are implemented at various stages of the
      early drug discovery process and play a central role in target validation and
      mode of action determination. The spectrum of methods ranges from genetic
      manipulations (e.g. knockout studies, mutation analyses and the construction of
      conditional mutants) to transcriptome and proteome expression profiling.
      Functional genomics supports antibacterial drug discovery by improving knowledge
      on gene function, bacterial physiology and virulence and the effects of
      antibiotics on bacterial metabolism.

PMID- 15993813
TI  - PAX of mind for pathway researchers.
AB  - Scientists seeking to understand the inner workings of cells have access to a
      multitude of pathway data resources. However, the representations of pathway data
      within these resources are not consistent or interchangeable. To facilitate easy
      information retrieval from a wide variety of pathway resources, such as signal
      transduction, gene regulation, molecular interaction and metabolic pathway
      databases, a broad effort in the biopathways community called BioPAX was formed.
      New biological pathway software applications built using the BioPAX standard will
      be able to integrate knowledge from multiple sources in a coherent and reliable
      way. This article reports the progress that the BioPAX work-group has made
      towards building and deploying the BioPAX data-exchange format for biological
      pathway data.

PMID- 15993818
TI  - A new assay of thermal-based avoidance test in freely moving mice.
AB  - The hot plate test is a standard way to measure nociceptive response latencies to
      a noxious thermal stimulus. Here we have modified the classic hot plate by
      allowing animals to escape to an adjacent chamber after exposure to the heated
      surface. In this test, the animals escape to the adjacent chamber after exposure
      to the hot plate set at 50 degrees C. Repeated exposure to the hot plate resulted
      in a facilitation of escape responses, as measured by a reduced latency to escape
      from the noxious thermal stimulus. Signs of nociceptive behavior, such as licking
      or jumping, were not affected in animals that received hot plate training. The
      reduction of escape latencies after repeated hot plate exposure might be a useful
      measure for studying the facilitation of escape responses. In addition, the
      modified hot plate described here might be useful in studying performance and
      memory deficits related to noxious thermal stimuli. PERSPECTIVE: We modified a
      hot plate to measure facilitation of escape responses to a noxious thermal
      stimulus. The measure of escape responses might be useful in the assessment of
      memory defects, evaluation of drug therapies, and the behavioral characterization
      of transgenic mice.

PMID- 15993819
TI  - Hyperpolarization-activated, cation-nonselective, cyclic nucleotide-modulated
      channel blockade alleviates mechanical allodynia and suppresses ectopic discharge
      in spinal nerve ligated rats.
AB  - Abnormal spontaneous firing is well described in axotomized sensory neurons and
      likely contributes to nerve injury-induced pain. The hyperpolarization-activated
      current I(h) initiates spontaneous, rhythmic depolarization in the sinoatrial
      node and central neurons. This study was undertaken to investigate the possible
      contribution of I(h) to primary afferent ectopic discharge and pain behavior in
      nerve-injured rats. Nerve injury was produced by tight ligation of lumbar spinal
      nerves (L5/6). Two weeks later, rats showed marked mechanical allodynia.
      Withdrawal thresholds were measured before and after administration of saline or
      the specific I(h) antagonist ZD7288 (1, 3, or 10 mg/kg, intraperitoneally).
      ZD7288 dose-dependently reversed mechanical allodynia. In a second experiment, we
      performed both in vivo and in vitro extracellular single unit recordings from
      teased dorsal root fascicles. Intravenous infusion (2.5 or 5 mg/kg) of ZD7288
      during a period of 10 minutes significantly blocked ectopic discharges in vivo.
      Perfusion (25 to 100 mumol/L) of ZD7288 for 5 minutes in vitro almost completely
      blocked ectopic discharges from large myelinated fibers (Abeta) while partially
      suppressing ectopic discharge from thinly myelinated fibers (Adelta). We conclude
      from these data that in axotomized sensory neurons, a ZD7288-sensitive current
      contributes to spontaneous discharges in myelinated fibers. Thus, I(h) might
      substantially contribute to the pathophysiology of nerve injury-related
      neuropathic pain. PERSPECTIVE: The current study investigated the mechanism of
      abnormal spontaneous discharges (ectopic discharges) from axotomized sensory
      afferents. Ectopic discharges are a main driving source of nerve injury-induced
      neuropathic pain. Understanding the mechanism of ectopic discharges and
      identifying how to control them will be useful toward developing new therapies.

PMID- 15993820
TI  - Effects of N-methyl-D-aspartate receptor antagonists on acute morphine-induced
      and l-methadone-induced antinociception in mice.
AB  - Although N-methyl-D-aspartate (NMDA) receptor antagonists clearly attenuate the
      development of tolerance to the antinociceptive effects of opioids, it is not
      clear whether they also alter acute opioid-induced antinociception. The present
      study was designed to assess NMDA/opioid interactions in C57BL/6 mice by
      examining various NMDA receptor antagonists of different selectivity in
      combination with the mu opioid receptor agonists morphine and l-methadone. A
      mouse hot plate procedure was used to assess the effects of morphine (0.1 to 10.0
      mg/kg) and l-methadone (0.1 to 5.6 mg/kg) alone and after pretreatment with the
      competitive NMDA receptor antagonist LY235959 (0.1 to 1.0 mg/kg), the glycine
      site NMDA receptor antagonist R(+)-HA-966 (10.0 to 56.0 mg/kg), or the polyamine
      site and NR2B selective NMDA receptor antagonist ifenprodil (3.2 to 10.0 mg/kg).
      Morphine and l-methadone produced dose- and time-dependent increases in 56
      degrees C hot plate latencies. At the doses tested, the NMDA receptor antagonists
      produced no effect on hot plate latencies. However, when these drugs were
      combined with morphine, latency to respond to the hot plate was significantly
      increased from morphine alone. Combinations of the NMDA receptor antagonist
      LY235959 and l-methadone produced similar increases in hot plate latencies;
      however, combinations of l-methadone with R(+)-HA-966 or ifenprodil did not
      increase hot plate latencies compared with l-methadone alone. These results
      suggest that a range of NMDA receptor antagonists potentiate morphine-induced
      antinociception, although the potentiation of l-methadone might be specific to
      the antagonist examined. PERSPECTIVE: The inclusion of low-dose NMDA receptor
      antagonists to opioids might be beneficial for the treatment of acute pain by
      enhancing the antinociceptive effects of the opioid.

PMID- 15993821
TI  - Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the
      spinal cord of a rat model of neuropathic pain.
AB  - Previous studies have shown that chemokines might play a role in the pathology of
      chronic pain. The purpose of this study was to provide an immunohistochemical
      description of the distribution of CX3CL1 (fractalkine) and its receptor CX3CR1
      in the rat spinal cord in a model of inflammatory pain induced by unilateral
      intraplantar complete Freund's adjuvant (CFA) and in a model of neuropathic pain
      induced by L5 spinal nerve ligation (modified Chung model or mSNL). In naive
      rats, CX3CL1 is found in the cytoplasm of neurons as shown by colocalization of
      CX3XL1 and NeuN. Similar distribution of CX3CL1 was observed after CFA, whereas
      after mSNL, CX3CL1 was not only observed in neurons but also found in astrocytes,
      as shown by colocalization of CX3CL1 and GFAP. Weak immunoreactivity for the
      CX3CL1 receptor, CX3CR1, was found in microglia in the spinal cord of either
      naive rats or rats with inflammation. However, after spinal nerve injury, CX3CR1
      LI was upregulated in microglia throughout the dorsal horn. PERSPECTIVE: This
      study shows that spinal nerve injury, but not peripheral inflammation, induces
      the expression of a chemokine, CX3CL1 (fractalkine), in astrocytes and
      upregulates CX3CR1 in microglia in the spinal cord. This selective regulation of
      CX3CL1 and its receptor, CX3CR1, suggests that these chemokines may represent new
      targets for the treatment of neuropathic pain.

PMID- 15993822
TI  - Epinephrine-induced excitation and sensitization of rat C-fiber nociceptors.
AB  - Although epinephrine (EPI) has been suggested to contribute to the pain and
      hyperalgesia associated with inflammation and nerve injury, there have been very
      few in vivo electrophysiologic studies of the effects of EPI on nociceptors. We
      found with the single-unit recording technique that the intradermal
      administration of EPI resulted in excitation of a group of C fibers and a
      decrease in the mechanical activation threshold in a non-overlapping group.
      Unexpectedly, the fibers that were neither excited nor demonstrated a decrease in
      threshold demonstrated as a group a significant increase in response to sustained
      suprathreshold mechanical stimuli, an effect not observed in the other 2 groups
      of C fibers. This identifies a novel response of C-fiber nociceptors to an
      inflammatory mediator and suggests it is present in a class of C fibers
      previously considered unresponsive to hyperalgesic inflammatory mediators.
      PERSPECTIVE: Our study provides support for the suggestion that EPI, a
      neuroendocrine stress hormone as well as an inflammatory mediator, might
      contribute to pain syndromes, especially in the setting of chronic stress.

PMID- 15993823
TI  - Remote nerve injection of mu opioid receptor adeno-associated viral vector
      increases antinociception of intrathecal morphine.
AB  - We have shown previously that using recombinant adeno-associated viral vector
      (rAAV) to up-regulate mu opioid receptors (muORs) in dorsal root ganglia (DRGs)
      increases the potency of subcutaneous morphine. Here we report an improved method
      of introducing rAAV-muOR viral vectors into DRGs. Instead of injecting the rAAV
      muOR gene directly into DRGs as shown before, the vector was introduced into the
      sciatic nerve of rats. Changes in muOR expression and antinociceptive effects of
      intrathecal morphine in rAAV-muOR rats were examined. Immunocytochemical studies
      showed that the transduced muORs were expressed in all types (ie, small, medium,
      and large) of DRG neurons. The expression of muORs in DRG neurons, quantified by
      Western blotting, was increased by 1.7-fold 4 weeks after the sciatic nerve
      injection. The up-regulation persisted for more than 6 months. The effects of
      intrathecal morphine on paw withdrawal latencies to heat were studied in rats
      inflamed with complete Freund's adjuvant. Compared with rats injected with rAAV
      containing the enhanced green fluorescent protein gene (rAAV-EGFP), the
      antinociceptive potency of intrathecal morphine in rAAV-muOR rats was
      significantly increased, and the effective dose (ED50) for morphine was 5.4-fold
      lower (rAAV-muOR: ED50 = 0.84 microg, confidence interval, 0.70-0.99 microg; rAAV
      EGFP: ED50 = 4.50 microg, confidence interval, 3.55-5.86 microg). With minimum
      tissue damage and a large persistent increase in the opioid potency, remote nerve
      injection of rAAV-muOR to up-regulate muORs could be a useful therapeutic
      strategy for the treatment of chronic pain. PERSPECTIVE: Injection of adeno
      associated viral vector containing the muOR gene into the sciatic nerve produces
      a significant up-regulation of muORs in DRGs for up to 6 months without producing
      any immune responses in the injected animals. This results in a 5.4-fold increase
      in the potency of intrathecal morphine.

PMID- 15993824
TI  - Statistical modeling of the response characteristics of mechanosensitive stimuli
      in the human esophagus.
AB  - It is believed that mechanical stimuli of the human gut activate afferents
      responding to either noxious or normal, physiologic stimuli. They might be able
      to sensitize without relation to the contractile state of the smooth muscle. The
      current study aimed to verify the above characteristics by using a statistical
      model based on correlation analysis. The esophagus was distended with a bag in 32
      healthy subjects by using an inflation rate of 25 mL/min. The luminal cross
      sectional areas and sensory ratings were determined during the distentions. The
      stimuli were repeated after relaxation of the smooth muscle with butylscopolamine
      and after sensitization with hydrochloride acid. A positive correlation between
      the sensory responses to distention was found in the non-painful and painful
      ranges, respectively, but correlations between non-painful and painful ratings
      were nonsignificant. Relaxation of the smooth muscle did not influence the
      correlations, and sensitization resulted in inter-individual differences and
      disappearance of the above clustering into painful and non-painful correlations.
      In conclusion, afferent nerves encoding high-threshold and low-threshold
      mechanical stimuli of the human esophagus are not correlated and thus probably
      represent different populations. The response characteristics have no physiologic
      relationship to the contractile state of the smooth muscle, and sensitization
      affects all types of afferents. PERSPECTIVES: The article adds information about
      sensory processing of mechanical gut stimuli in human beings. This might increase
      our understanding of visceral pain in health and disease and guide the
      statistical analysis of experimental data obtained in the gastrointestinal tract.

PMID- 15993825
TI  - Sex differences in the associations among psychological factors and pain report:
      a novel psychophysical study of patients with chronic low back pain.
AB  - Previous studies have consistently suggested that there are sex differences in
      pain report, but there is no consensus regarding sex differences in the
      associations among psychological factors and pain report. This cross-sectional
      study used a novel, clinically relevant, psychophysical pain-induction technique
      to examine sex differences between sensory and affective pain report and sex
      differences in the association of depression, pain related anxiety, and
      catastrophizing with pain report. Patients with chronic low back pain (N = 53)
      were recruited from an outpatient spine clinic, and those consenting completed
      self-report measures of pain-related anxiety, depression, pain catastrophizing,
      and pain. A measure of induced low back pain was obtained by having study
      participants perform a protocol on the MedXtrade mark Low-Back Exercise
      Apparatus. Our results indicated that no sex differences were detected in
      psychological factors and self-reported or induced low back pain. However, the
      relationships between pain related anxiety and self-report of low back pain (z =
      2.51, P < .05) and between pain-related anxiety and induced low back pain (z =
      3.00, P < .05) were significantly stronger in men than women. These findings
      suggest that anxiety was linked to self-reported and induced low back pain for
      men, but not for women. PERSPECTIVE: Results of this study suggest that pain
      related anxiety has a stronger association with psychophysical and clinical
      reports of low back pain for men.

PMID- 15993826
TI  - Self-efficacy for managing pain is associated with disability, depression, and
      pain coping among retirement community residents with chronic pain.
AB  - Little is known about cognitive and behavioral factors that influence older
      adults' adjustment to chronic pain. The objective of this study was to
      investigate the relationship of self-efficacy for managing pain to reports of
      pain intensity, pain-related disability, depressive symptoms, and pain coping
      strategy use among 140 retirement community residents (88% female; age mean =
      81.7, range 66-99 years) with chronic pain. The 8-item Arthritis Self-Efficacy
      Scale, modified to specify pain rather than arthritis, demonstrated good
      psychometric characteristics (Cronbach alpha = .89, minimal floor and ceiling
      effects, and validity) in this sample. Controlling for age, gender, and pain
      intensity, self-efficacy was associated significantly and negatively with pain
      related disability and depressive symptoms (P values < .001), and positively with
      use of pain coping strategies previously found to be associated with better
      outcomes (task persistence, exercise/stretch, coping self-statements, activity
      pacing; P values < .05). Self-efficacy for managing pain appears to be important
      in the adjustment of older adults with pain. Research is needed to determine
      whether interventions designed to increase self-efficacy improve quality of life
      and prevent functional declines in this population. PERSPECTIVE: Among retirement
      community residents (mean age of 82 years) with chronic pain, higher self
      efficacy for managing pain is associated with less disability and depression and
      with the use of pain coping strategies related to better adjustment. This
      suggests the potential value of interventions to increase self-efficacy in this
      population.

PMID- 15993827
TI  - Crossing roads safely: an experimental study of age differences in gap selection
      by pedestrians.
AB  - The over-representation of older pedestrians in serious injury and fatal crashes
      compared to younger adults may be due, in part, to age-related diminished ability
      to select gaps in oncoming traffic for safe road-crossing. Two experiments are
      described that examine age differences in gap selection decisions in a simulated
      road-crossing environment. Three groups of participants were tested, younger (30
      45 years), young-old (60-69 years) and old-old (>75 years). The results showed
      that, for all age groups, gap selection was primarily based on vehicle distance
      and less so on time-of-arrival. Despite the apparent ability to process the
      distance and speed of oncoming traffic when given enough time to do so, many of
      the old-old adults appeared to select insufficiently large gaps. These results
      are discussed in terms of age-related physical, perceptual and cognitive
      limitations and the ability to compensate for these limitations. Practical
      implications for road safety countermeasures are also highlighted, particularly
      the provision of safe road environments and development of behavioural and
      training packages.

PMID- 15993828
TI  - The modality shift effect and the effectiveness of warning signals in different
      modalities.
AB  - Which is better, a visual or an auditory warning signal? Initial findings
      suggested that an auditory signal was more effective, speeding reaction to a
      target more than a visual warning signal, particularly at brief foreperiods
      [Bertelson, P., & Tisseyre, F. (1969). The time-course of preparation:
      confirmatory results with visual and auditory warning signals. Acta Psychologica,
      30. In W.G. Koster (Ed.), Attention and Performance II (pp. 145-154); Davis, R.,
      & Green, F. A. (1969). Intersensory differences in the effect of warning signals
      on reaction time. Acta Psychologica, 30. In W.G. Koster (Ed.), Attention and
      Performance II (pp. 155-167)]. This led to the hypothesis that an auditory signal
      is more alerting than a visual warning signal [Sanders, A. F. (1975). The
      foreperiod effect revisited. Quarterly Journal of Experimental Psychology, 27,
      591-598; Posner, M. I., Nissen, M. J., & Klein, R. M. (1976). Visual dominance:
      an information-processing account of its origins and significance. Psychological
      Review, 83, 157-171]. Recently [Turatto, M., Benso, F., Galfano, G., & Umilta, C.
      (2002). Nonspatial attentional shifts between audition and vision. Journal of
      Experimental Psychology: Human Perception and Performance, 28, 628-639] found no
      evidence for an auditory warning signal advantage and showed that at brief
      foreperiods a signal in the same modality as the target facilitated responding
      more than a signal in a different modality. They accounted for this result in
      terms of the modality shift effect, with the signal exogenously recruiting
      attention to its modality, and thereby facilitating responding to targets
      arriving in the modality to which attention had been recruited. The present study
      conducted six experiments to understand the cause of these conflicting findings.
      The results suggest that an auditory warning signal is not more effective than a
      visual warning signal. Previous reports of an auditory superiority appear to have
      been caused by using different locations for the visual warning signal and visual
      target, resulting in the target arriving at an unattended location when the
      foreperiod was brief. Turatto et al.'s results were replicated with a modality
      shift effect at brief foreperiods. However, it is also suggested that previous
      measures of the modality shift effect may still have been confounded by a
      location cuing effect.

PMID- 15993829
TI  - Learning a new human-computer alphabet: the role of similarity and practice.
AB  - Two purposes motivated this study: (a) to quantify the difficulty in learning
      various symbols of the alphabet used to enter data into a personal digital
      assistant (PDA), and (b) to investigate the interaction of item difficulty with
      practice conditions that promote varying levels of cognitive effort. Levels of
      compatibility between members of the PDA alphabet and English were quantified
      through introspective ratings in Experiment 1 and objective performance measures
      in Experiment 2. Three levels of item compatibility were learned under conditions
      of proactive or retroactive augmented information in Experiment 3. Contrary to
      expectations, the item similarity effect did not interact with practice schedules
      -a retroactive augmented information condition resulted in degraded levels of
      acquisition performance, but superior retention levels, compared to the proactive
      condition. These findings are discussed in terms of the relative merits of
      cognitive effort in skill acquisition.

PMID- 15993830
TI  - Effects of stimulus-stimulus compatibility and stimulus-response compatibility on
      response inhibition.
AB  - Previous studies demonstrated that interference control in stimulus-stimulus
      compatibility tasks slowed down stopping in the stop signal task (e.g., Kramer,
      A. F., Humphrey, D. G., Larish, J. F., Logan, G. D., & Strayer, D. L. (1994).
      Aging and inhibition: beyond a unitary view of inhibitory processing in
      attention. psychology and aging, 9, 491-512). In the present study, the impact of
      stimulus-stimulus compatibility and stimulus-response compatibility on response
      inhibition is further investigated. In Experiment 1, the stop signal task was
      combined with a traditional horizontal Simon task and with a vertical variant.
      For both dimensions, stopping responses was prolonged in incompatible trials, but
      only when the previous trial was compatible. In Experiment 2, the Simon task was
      combined with a spatial Stroop task in order to compare the effects of stimulus
      stimulus and stimulus-response compatibility. The results demonstrated that both
      types of compatibility influenced stopping in a similar way. These findings are
      in favor of the hypothesis that response inhibition in the stop signal task and
      interference control in conflict tasks rely on similar mechanisms.

PMID- 15993831
TI  - Occurrence of extended spectrum beta-lactamase enzymes in clinical isolates of
      Klebsiella species from Harar region, eastern Ethiopia.
AB  - Extended Spectrum beta-Lactamases (ESBLs) producer and multidrug resistant
      Klebsiella spp. are becoming a major nosocomial pathogen globally. There are no
      documented reports yet on the occurrence of ESBL enzymes in Klebsiella spp.
      species from Ethiopia. This study was undertaken to isolate and determine the
      occurrence of ESBLs and multi-drug resistant Klebsiella spp. in different
      clinical samples obtained from patients. A cross-sectional survey was conducted
      in four different hospitals of Harar region (Hiwot Fana, Misrak-Arbegnoch, Police
      and Army) from December 2003 to February 2004. Three hundred and eighty four
      clinical specimens (202 sputum, 164 urine and 18 pus) were collected from
      patients admitted in different wards. Antimicrobial susceptibilities were
      performed on 57 clinical isolates by standard disk diffusion procedures against
      eight antimicrobial agents. The ESBLs detection was made by using cefotaxime and
      ceftazidime alone and in combination with clavulanate. A total of 57 (15%)
      Klebsiella spp. were isolated from 384 patients. Of the 57 isolates, 33 (58%)
      were from sputum, 18 (31.5%) from urine and 6 (10.5%) from pus. Of the 57
      Klebsiella spp., 54 (94.7%) were identified as K. pneumoniae and 3 (5.3%) as K.
      oxytoca. Resistance was found against cephalosporins [cefotaxime (39.0%),
      cefoxitin (39.0%), ceftazidime (40.0%), ceftriaxone (40.0%), cephalothin
      (42.0%)], chloramphenicol (70.0%), gentamicin (61.0%) and trimethoprim
      sulphamethoxazole (65.0%). Analyzed Klebsiella isolates were characterized also
      by a high degree of multi-resistance (67.0%). In 19/57 (33.3%) of the Klebsiella
      isolates, ESBL production was detected. Rates of detection of ESBL producers were
      42.1, 26.3, 26.3 and 5.3% in Hiwot-Fana, Misrak-Arbegnoch, Police and Army
      hospitals, respectively. Multi-drug resistant isolates were more prevalent among
      the ESBLs producers (95.0%) than non-producers (53.0%) (p=0.24). In conclusion,
      our results show that awareness of ESBL production by Klebsiella spp. is
      clinically important. In the absence of infection control measures, ESBL
      producing organisms readily pass horizontally from patient to patient. These
      strains also transiently colonize the hands of hospital staff members, thereby
      facilitating patient-to-patient transmission of the organism.

PMID- 15993832
TI  - Detailed assessment of microhabitat suitability for Aedes aegypti (Diptera:
      Culicidae) in Buenos Aires, Argentina.
AB  - Little information is available on the ecology of Aedes aegypti Linnaeus at the
      southern extreme of its distribution (Buenos Aires, Argentina), particularly on
      microhabitat suitability. The aim of our study was to identify at a detailed
      scale, microhabitat factors that correlate with the presence of preimaginal
      stages of the mosquito. In March 2001, we performed a spatial census of all
      containers located in a 1 ha patch within a cemetery in Buenos Aires City. On a
      reference map (1:700) we plotted the position of graves and surrounding
      corridors, the location of containers, the shade projected by each plant between
      10:00 and 16:00 h and vegetation cover. We classified vegetation by height,
      substrate by composition and shadow by level of exposure to sunlight. We
      performed univariate and multivariate logistic regression analyses with nine
      constructed independent variables, some of them at scales of 0.5, 1, 2, 3, and 10
      m. Of 850 receptacles examined, 101 contained preimaginal stages of Ae. aegypti.
      Level of exposure to sunlight, type of substratum, vegetation height and distance
      of containers to vegetation were significantly associated with the presence of
      breeding sites at the studied scales. Final multivariate models were significant
      at scales of 2 m (chi(3)2=25.693, p<0.001) and 3m (chi(3)2=26.440, p<0.001), and
      65.9 and 66.8% of our data were correctly classified, respectively, for each
      scale. Our results suggest that sites less exposed to sunlight, with taller and
      closer vegetation, and in shaded and vegetated neighbourhoods were the most
      favourable microhabitats for Ae. aegypti breeding.

PMID- 15993833
TI  - Oral administration of a live Aro attenuated Salmonella vaccine strain expressing
      14-kDa Schistosoma mansoni fatty acid-binding protein induced partial protection
      against experimental schistosomiasis.
AB  - We report the oral vaccination of SWISS mice with an Aro attenuated Salmonella
      enterica var. Typhimurium vaccine strain expressing the 14-kDa Schistosoma
      mansoni antigen, Sm14. Bacterial adjuvants, including (i) Lactococcus lactis
      expressing interleukin-12 (IL-12) and (ii) Lactobacillus delbrueckii UFV-H2b20,
      were also employed in oral immunization assays. Detection assays to specific IgG
      and IgA anti-Sm14 antibodies were performed to evaluate humoral immune responses
      in vaccinated mice. An increase in specific IgG titers was observed; however, no
      IgA production was detected. The protection levels against schistosomiasis (34.9
      49.5%) obtained with all experimental formulations in this work were very similar
      to values reported by previous studies, which used purified recombinant Sm14 for
      parenteral vaccination of mice. There was a slight reduction in hepatic
      granulomas of mice vaccinated with Salmonella. Oogram studies showed diminished
      numbers of S. mansoni eggs in the intestinal wall of vaccinated mice, but
      individual female worm fecundity did not seem to be affected by our immunization
      protocol.

PMID- 15993834
TI  - Feeding rates, nutritional status and flight dispersal potential of peridomestic
      populations of Triatomainfestans in rural northwestern Argentina.
AB  - Triatoma infestans, the main vector of Chagas disease in Southern Cone countries,
      frequently infests peridomestic structures housing domestic animals. A total of
      814 T. infestans collected from 35 different peridomestic sites in rural
      northwestern Argentina over 1-4 consecutive seasons was examined for recent blood
      meals and nutritional status. Bugs from goat or pig corrals had lower qualitative
      nutritional status and mean weight to length ratios (W/L) than those captured in
      chicken coops. Males systematically had lower qualitative nutritional status and
      W/L than females. Using logistic multiple regression, the daily feeding rates of
      T. infestans were significantly associated with season and stage but not ecotope,
      whereas the proportion of well-fed bugs varied significantly with all three
      factors. The seasonal trends in feeding rates and nutritional status were
      consistent with the local availability and breeding timing of domestic animals.
      The observed data fed into an empirical model predicted that the probability of
      flight initiation would peak in summer from pig or goat corrals, not chicken
      coops, and be insignificant in all ecotopes in spring and fall. Male T. infestans
      outnumbered females as potential fliers. This is the first study conducted in
      well-defined habitat units that shows significant heterogeneities in the feeding
      rates and nutritional status of triatomine populations linked to host
      demographics and management, and how these affect flight dispersal potential over
      seasons. Peridomestic bug populations are of great relevance as a source of
      domestic reinfestation and for the elimination of T. infestans.

PMID- 15993835
TI  - Microfluidic systems and proteomics: applications of the electrocapture
      technology to protein and peptide analysis.

PMID- 15993836
TI  - Protein secretion systems in Fusobacterium nucleatum: genomic identification of
      Type 4 piliation and complete Type V pathways brings new insight into mechanisms
      of pathogenesis.
AB  - Recent genomic analyses of the two sequenced strains F. nucleatum subsp.
      nucleatum ATCC 25586 and F. nucleatum subsp. vincentii ATCC 49256 suggested that
      the major protein secretion systems were absent. However, such a paucity of
      protein secretion systems is incongruous with F. nucleatum pathogenesis.
      Moreover, the presence of one or more such systems has been described for every
      other Gram-negative organism sequenced to date. In this investigation, the
      question of protein secretion in F. nucleatum was revisited. In the current
      study, the absence in F. nucleatum of a twin-arginine translocation system (TC
      #2.A.64.), a Type III secretion system (TC #3.A.6.), a Type IV secretion system
      (TC #3.A.7.) and a chaperone/usher pathway (TC #1.B.11.) was confirmed. However,
      contrary to previous findings, our investigations indicated that a Type I protein
      secretion system was also absent from F. nucleatum. In contrast, members of the
      holin family (TC #1.E) and the machinery required for a Type 4
      piliation/fimbriation system (TC #3.A.15.2.) were identified using a variety of
      bioinformatic tools. Furthermore, a complete range of proteins resembling members
      of the Type V secretion pathway, i.e., the Type Va (autotransporter; TC
      #1.B.12.), Type Vb (two-partner secretion system; TC #1.B.20.) and Type Vc (YadA
      like trimeric autotransporter; TC #1.B.42.), was found. This work provides new
      insight into the protein secretion and virulence mechanisms of F. nucleatum.

PMID- 15993837
TI  - Plastid DNA polymerases from higher plants, Arabidopsis thaliana.
AB  - Previously, we described a novel DNA polymerase, designated as OsPolI-like, from
      rice. The OsPolI-like showed a high degree of sequence homology with the DNA
      polymerase I of cyanobacteria and was localized in the plastid. Here, we describe
      two PolI-like polymerases, designated as AtPolI-like A and AtPolI-like B, from
      Arabidopsis thaliana. In situ hybridization analysis demonstrated expression of
      both mRNAs in proliferating tissues such as the shoot apical meristem. Analysis
      of the localizations of GFP fusion proteins showed that AtPolI-like A and AtPolI
      like B were localized to plastids. AtPolI-like B expression could be induced by
      exposure to the mutagen H(2)O(2). These results suggested that AtPolI-like B has
      a role in the repair of oxidation-induced DNA damage. Our data indicate that
      higher plants possess two plastid DNA polymerases that are not found in animals
      and yeasts.

PMID- 15993838
TI  - Long-term RNA interference from optimized siRNA expression constructs in adult
      mice.
AB  - DNA constructs for small interfering RNA (siRNA) expression in mammalian cells
      have the potential for longer-term target gene knockdown than synthetic siRNAs.
      We compared in adult mice the efficacy and longevity of target gene knockdown
      from siRNA expression cassettes contained in plasmids, PCR-generated linear
      constructs or PCR constructs containing "dumbbell" ends using the hydrodynamic
      delivery method. Plasmid siRNA expression constructs were more effective than PCR
      constructs for target gene knockdown. The efficacy of the PCR constructs was
      improved by addition of short extensions beyond the transcription termination
      signal and greatly improved by addition of dumbbell ends. Constructs containing
      the H1 promoter were significantly less effective in mice than those containing
      the U6 promoter, whereas both promoters functioned equally well in cultured
      cells. Target gene knockdown perdured for at least 20 weeks in mice after
      delivery of either PCR or plasmid siRNA expression cassettes. These results will
      help guide RNAi vector design.

PMID- 15993839
TI  - Polarized localization of vitamin C transporters, SVCT1 and SVCT2, in epithelial
      cells.
AB  - Messenger RNA of homologous sodium-vitamin C cotransporters, SVCT1 and SVCT2,
      were found in the intestine. Studies using cultured intestinal cells suggested an
      apical presence of SVCT1 but the function of SVCT2 was unknown. Here, we showed
      that enterocytes from heterozygous SVCT2-knockout mice had lower sodium-dependent
      vitamin C accumulation compared to those from the wildtype. Thus, SVCT2 appears
      to be functional in enterocytes. We then tested whether SVCT2 could have a
      redundant function as SVCT1 by constructing and expressing EGFP-tagged SVCTs in
      intestinal Caco-2 and kidney MDCK cells. In confluent epithelial cells, SVCT1
      protein expressed predominantly on the apical membrane. SVCT2, in contrast,
      accumulated at the basolateral surface. Functionally, SVCT1 expression led to
      more transport activity from the apical membrane, while SVCT2 expression only
      increased the uptake under the condition when basolateral membrane was exposed.
      This differential epithelial membrane distribution and function suggests non
      redundant functions of these two isoforms.

PMID- 15993840
TI  - Rational design of an EGF-IL18 fusion protein: implication for developing tumor
      therapeutics.
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine. This protein has a role in
      regulating immune responses and exhibits significant anti-tumor activities.
      Epidermal growth factor (EGF) is an important growth factor that plays a central
      role in the regulation of cell cycle and differentiation. It was proposed that a
      targeted delivery of IL-18 by generation of IL-18-EGF fusion protein might
      decrease adverse effects and result in enhancing cytotoxic and antitumor
      activities. In the present study, a fusion protein, consisting of EGFR binding
      domain fused to human IL-18 mature peptide via a linker peptide of (Gly(4)Ser) 3,
      was constructed and expressed in the insect cell line Sf9 using Bac-to-Bac
      baculovirus expression system. We showed that the purified recombinant fusion
      protein induced similar levels of IFN-gamma to that of native IL-18 protein in
      human PBMC in the presence of ConA. Furthermore, EGF receptor competitive test in
      human epithelial cancer A431 cell line showed that EGF-IL18 fusion protein can
      specifically bind with EGFR by competing with native EGF protein. These suggest
      that this rationally designed protein can be further developed as novel tumor
      therapeutics.

PMID- 15993842
TI  - Boosting classifier for predicting protein domain structural class.
AB  - A novel classifier, the so-called "LogitBoost" classifier, was introduced to
      predict the structural class of a protein domain according to its amino acid
      sequence. LogitBoost is featured by introducing a log-likelihood loss function to
      reduce the sensitivity to noise and outliers, as well as by performing
      classification via combining many weak classifiers together to build up a very
      strong and robust classifier. It was demonstrated thru jackknife cross-validation
      tests that LogitBoost outperformed other classifiers including "support vector
      machine," a very powerful classifier widely used in biological literatures. It is
      anticipated that LogitBoost can also become a useful vehicle in classifying other
      attributes of proteins according to their sequences, such as subcellular
      localization and enzyme family class, among many others.

PMID- 15993841
TI  - Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B.
AB  - Rebamipide accelerates healing of gastric ulcers and gastritis but its actions on
      gastric cancer are not known. Survivin, an anti-apoptosis protein, is
      overexpressed in stem, progenitor, and cancer cells. In gastric cancer, increased
      and sustained survivin expression provides survival advantage and facilitates
      tumor progression and resistance to anti-cancer drugs. Aurora-B kinase is
      essential for chromosome alignment and mitosis progression but surprisingly its
      role in gastric cancer has not been explored. We examined in human gastric cancer
      AGS cells: (1) survivin expression, (2) localization of survivin and Aurora-B,
      (3) cell proliferation, and (4) effects of specific survivin siRNA and/or
      rebamipide (free radical scavenging drug) on survivin and Aurora-B expression and
      cell proliferation. Survivin and Aurora-B are strongly expressed in human AGS
      gastric cancer cells and co-localize during mitosis. Survivin siRNA significantly
      reduces AGS cell viability. Rebamipide significantly downregulates in AGS cell
      survivin expression, its association with Aurora-B and cell proliferation.
      Rebamipide-induced downregulation of survivin is at the transcription level and
      does not involve ubiquitin-proteasome pathway.

PMID- 15993843
TI  - Inhibition of melanoma cell proliferation by resveratrol is correlated with
      upregulation of quinone reductase 2 and p53.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene) is a grape-derived polyphenol under
      intensive study for its potential in cancer prevention. In the case of cultured
      human melanoma cells, no one to our knowledge has investigated whether
      resveratrol exerts similar anti-proliferative activities in cells with different
      metastatic potential. Therefore, we examined the effects of this polyphenol on
      the growth of weakly metastatic Line IV clone 3 and on autologous, highly
      metastatic Line IV clone 1 cultured melanoma cells. Comparable inhibition of
      growth and colony formation resulted from treatment by resveratrol in both cell
      lines. Flow cytometric analysis revealed that resveratrol-treated clone 1 cells
      had a dose-dependent increase in S phase and a concomitant reduction in the G(1)
      phase. No detectable change in cell cycle phase distribution was found in
      similarly treated clone 3 cells. Western blots demonstrated a significant
      increase in the expression of the tumor suppressor gene p53, without a
      commensurate change in p21 and several other cell cycle regulatory proteins in
      both cell types. Chromatography of Line IV clone 3 and clone 1 cell extracts on
      resveratrol affinity columns revealed that the basal expression of
      dihydronicotinamide riboside quinone reductase 2 (NQO2) was higher in Line IV
      clone 1 than clone 3 cells. Levels of NQO2 but not its structural analog NQO1
      were dose-dependently increased by resveratrol in both cell lines. We propose
      that induction of NQO2 may relate to the observed increased expression of p53
      that, in turn, contributes to the observed suppression of cell growth in both
      melanoma cell lines.

PMID- 15993844
TI  - TEM-8 and tubule formation in endothelial cells, its potential role of its vW/TM
      domains.
AB  - BACKGROUND AND AIMS: Tumour endothelial marker-8 (TEM-8) has been found to be
      selectively up regulated in tumour-associated endothelial cells, it is implicated
      in tumour specific angiogenesis, but its mechanism in angiogenesis is not
      defined. METHODS: A ribozyme transgene (TEM-8) was cloned into a suitable
      mammalian expression vector (pc DNA 3.1-GFP-NT) and transfected into HECV cells.
      Various domains of TEM-8 were designed and cloned into pEF6/V5-His TOPO TA vector
      and transfected into Chinese Hamster ovarian cells (CHO), which do not form
      tubules and do not express TEM-8 in general (CHO(vW), CHO(TM), CHO(vW/TM),
      CHO(AE), CHO(AC), CHO(IC), and CHO(FL) domains, respectively). The effect of TEM
      8 knocked out HECV cells was tested (by angiogenesis and migration assays), and
      the effect of each cleavage domain of TEM-8 was tested by microtubule formation
      assay. RESULTS: TEM-8 stable transfectants (HECV(DeltaTEM8a)) manifested a
      complete loss of TEM-8 gene expression at mRNA and protein levels. In contrast,
      control GFP plasmid (HECV(pControl)) and wild-type HECV cells (HECV(WT)) had
      similar levels of TEM-8 expression. TEM-8 transfected cell (HECV(DeltaTEM8a))
      significantly decreased the micro-vessels formation compared with controls
      (HECV(pControl)) (mean+/-SE, 20.3+/-4.03 microm; p=0.0086 vs. control 39.5+/-10.1
      microm), and migration (38.52+/-2.17; p<0.05 vs. control 80.23+/-3.19), and micro
      vessel formation of HECV(DeltaTEM8a) cell was also reduced compared with wild
      type (HECV(WT)) (mean+/-SE, 20.3+/-4.03 microm; p=0.0078 vs. wild-type 42.5+/-9.1
      microm) and migration (38.52+/-2.17microm; p<0.05 vs. wild-type 82.4+/-4.45
      microm). vW together with transmembrane domains of TEM-8 (CHO(vW/TM)) and full
      length CHO(FL) showed formation of tubule-like structure in CHO cells, whereas
      the other domains showed no effect. CONCLUSION: Targeting the TEM-8 gene by way
      of a hammerhead ribozyme knocks out TEM-8 cells, and is an effective way to
      reduce the micro-vessel formation or migration potential in tumour-associated
      endothelial cell through its vW domain. These results suggest that the vW domain
      together with the transmembrane domain of TEM-8 may play an important biological
      role in TEM-8 related tubule formation.

PMID- 15993845
TI  - Protection from oxidative stress by methionine sulfoxide reductases in RPE cells.
AB  - We investigated the role of methionine sulfoxide reductases (Msrs) in oxidant
      stress-induced cell death in retinal pigmented epithelial (RPE) cells. In RPE
      cells exposed to varying doses of H(2)O(2), gene expression of MsrA and hCBS-1
      (the human analog of MsrB2) increased in a dose-dependent and time-dependent
      manner with maximal increase with 150 microM H(2)O(2) in 24h. H(2)O(2) treatment
      resulted in the generation of reactive oxygen species and activation of caspase
      3. Confocal microscopic and protein analysis showed an increase in MsrA
      expression in cytosol and mitochondria. Silencing of MsrA resulted in caspase 3
      induction and accentuated cell death from H(2)O(2). Focal, strong
      immunoreactivity for MsrA was observed in sub-RPE macular drusen from patients
      with age-related macular degeneration. In summary, our data show that MsrA and
      hCBS-1 are up-regulated in oxidative stress to counteract injury to RPE.

PMID- 15993846
TI  - Elevated expression of TARC (CCL17) and MDC (CCL22) in models of cigarette smoke
      induced pulmonary inflammation.
AB  - TARC (CCL17) and MDC (CCL22) are well-known chemoattractants for Th2 cells. Here,
      we evaluated the role of both chemokines for cigarette smoke-induced airway
      inflammation. The expression profiles of MDC, TARC, and their receptor CCR4 were
      analyzed in models of acute and chronic cigarette smoke-induced airway
      inflammation that is characterized by a Th1 immune response. The results were
      compared to the expression of both chemokines in models of idiopathic pulmonary
      fibrosis and acute asthma, which are associated with a Th2 immune response. The
      expression of MDC and TARC was found to be elevated in all lung inflammation
      models. In contrast to the findings in the asthma and lung fibrosis models, the
      increased expression of MDC and TARC in the cigarette-smoke model was not
      associated with an increased infiltration of Th2 cells into smoke-treated lungs.
      Our data indicate that instead of Th2 cells, airway epithelial cells expressing
      CCR4 might be the principal targets for MDC and TARC released from alveolar
      macrophages during cigarette smoke-induced airway inflammation.

PMID- 15993847
TI  - Cloning and functional characterization of the rat alpha2B-adrenergic receptor
      gene promoter region: Evidence for binding sites for erythropoiesis-related
      transcription factors GATA1 and NF-E2.
AB  - In the rat, the alpha2B-adrenergic receptor (alpha2B-AR) is encoded by the rat
      non-glycosylated (RNG) gene and is primarily expressed in the kidney, brain and
      liver of adult animals. High levels of alpha2B-AR are also found during fetal
      life in the placenta, liver and blood, where it is borne by cells of the
      erythropoietic lineage. As a first step to define the mechanisms responsible for
      the spatio-temporal pattern of alpha2B-AR expression, a genomic fragment
      containing 2.8 kb of the 5'-flanking region, the ORF and approximately 20 kb of
      the 3'-flanking region of the RNG gene was isolated. RNase protection assays
      performed on RNA from placenta or kidney using a series of riboprobes permitted
      to locate the transcription start site 372 bases upstream from the start codon.
      Transient transfection of various cells, including rat proximal tubule in primary
      culture, with constructs containing luciferase as a reporter gene demonstrated
      that: (i) the 5'-flanking region exhibited a strong and sense-dependent
      transcriptional activity and (ii) the 332 bp fragment (-732/-401 relative to the
      start codon), which lacks a TATA box but contains Sp1 sites, is sufficient to
      drive expression. Analysis of chromatin susceptibility to DNaseI digestion
      identified two hypersensitive sites (HS1 and HS2) located 1.7 and 1.0 kb,
      respectively, upstream from ATG and containing recognition sequences for
      erythroid transcription factors. EMSA showed specific binding of GATA1 and NF-E2
      to these elements. Taken together, the results suggest that the chromatin
      environment in the vicinity of these boxes plays a critical role for alpha2B-AR
      expression during fetal life.

PMID- 15993848
TI  - 17-Allylamino-17-demethoxygeldanamycin overcomes TRAIL resistance in colon cancer
      cell lines.
AB  - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a promising
      candidate for treatment of cancer, but displays variable cytotoxicity in cell
      lines. The mechanisms of sensitivity and resistance have not been fully
      elucidated; both AKT and NF-kappaB pathways may modulate cytotoxic responses. We
      have shown that the Hsp90 inhibitor 17-AAG enhances the cytotoxicity of
      oxaliplatin in colon cancer cell lines through inhibition of NF-kappaB. We
      analyzed the effects of TRAIL and 17-AAG in combination in a series of nine colon
      cancer cell lines and characterized activation of the pathways to apoptosis.
      IC(50) values for a 72 h exposure to TRAIL ranged from 30 to 4000 ng/ml.
      Cytotoxicity assays demonstrated additivity or synergism of the TRAIL/17-AAG
      combination in all cell lines, with combination indices at IC(50) ranging from
      0.53 to 1. The sensitizing effect of 17-AAG was greater in the TRAIL-resistant
      cell lines. In TRAIL-resistant cell lines, the combination of 17-AAG and TRAIL
      resulted in activation of both extrinsic and intrinsic apoptotic pathways, though
      with quantitative differences between HT29 and RKO cells: differential effects of
      17-AAG on AKT and NF-kappaB characterized these cell lines. In both cell lines,
      the combination also led to down-regulation of X-linked inhibitor of apoptosis
      protein (XIAP) and enhanced activation of caspase-3. We conclude that either AKT
      or NF-kappaB may promote resistance to TRAIL in colon cancer cells, and that the
      ability of 17-AAG to target multiple putative determinants of TRAIL sensitivity
      warrants their further investigation in combination.

PMID- 15993849
TI  - Effects of ethanol on cytokine generation and NFkappaB activity in human lung
      epithelial cell.
AB  - Alcohol abuse is associated with enhanced risk for pulmonary infections, but the
      mechanisms remain obscure. We assessed whether ethanol reduced generation of
      cytokines from a human lung epithelial cell line (A549) in vitro and if effects
      on the NFkappaB transcription factor were involved. Exposure of A549 to ethanol
      (0.1-1%) dose-dependently inhibited (by 15-49%) the release of G-CSF and IL-8,
      but not of M-CSF, triggered by IL1beta or TNFalpha. Ethanol also inhibited by 49%
      the IL-1beta stimulated translocation of the p65 subunit of NFkappaB from the
      cytoplasm into the nucleus. Using a kappaB binding and luciferase coupled
      construct, transfected into A549 cells, we found that 1% ethanol specifically
      reduced IL-1beta and TNFalpha induced luciferase activity with 34 and 40%,
      respectively. Thus, in vitro exposure of lung epithelial cells to ethanol reduced
      the generation of cytokines, as well as translocation and gene activation by
      NFkappaB.

PMID- 15993850
TI  - A novel CYP2A6*20 allele found in African-American population produces a
      truncated protein lacking enzymatic activity.
AB  - Human CYP2A6 is a cytochrome P450 (CYP) isoform responsible for the metabolism of
      nicotine, coumarin, tegafur, and valproic acid, and metabolic activation of
      nitrosamines. Genetic polymorphisms of the CYP2A6 gene are a major causal factor
      of the large interindividual differences in nicotine metabolism. In the present
      study, we identified a novel allele, termed CYP2A6*20, in an African-American
      population. The allele possesses the deletion of two nucleotides in exon 4
      resulting in a frame-shift from codon 196 and an early stop codon at 220 (exon 5)
      as well as three synonymous SNPs of G51A (G51A in cDNA), T5684C (T1191C), and
      C6692G (C1546G, 3'-untranslated region). The allele frequency in the African
      American population (n=96) was 1.6% (95% confidence interval, 0.6-4.5%). In
      contrast, the CYP2A6*20 allele was not found in Caucasians (European-American)
      (n=185), Japanese (n=184) and Korean (n=209) populations. To investigate the
      effects of the polymorphism on the enzymatic activities, we expressed a wild type
      or variant (deletion of two nucleotides) CYP2A6 together with NADPH-CYP reductase
      in Escherichia coli. SDS-PAGE and immunoblot analyses demonstrated that truncated
      CYP2A6 protein was produced from the variant allele, although detected mRNA was
      the predicted size by reverse transcriptional-polymerase chain reaction. Coumarin
      7-hydroxylation and nicotine C-oxidation, which are typical CYP2A6 activities,
      were completely abolished in the E. coli membrane expressing the variant allele.
      In vivo nicotine metabolism was evaluated using the cotinine/nicotine ratio 2 h
      after the chewing of one piece of nicotine gum. Two CYP2A6*1/CYP2A6*20
      heterozygotes and a single CYP2A6*17/CYP2A6*20 heterozygote revealed lower
      cotinine/nicotine ratios compared with CYP2A6*1/CYP2A6*1 subjects (1.6 and 4.5,
      and 1.8 versus 9.5+/-5.4, n=52, respectively). We found a novel CYP2A6*20 allele
      in African-American subjects which codes a truncated protein lacking enzymatic
      activity.

PMID- 15993851
TI  - S-15261, a new anti-hyperglycemic agent, reduces hepatic glucose production
      through direct and insulin-sensitizing effects.
AB  - S-15261 is a new oral anti-hyperglycemic agent that increases insulin sensitivity
      in various insulin-resistant animal models. The aim of this study was to
      determine the short- and long-term effects of S-15261 and its metabolites (S
      15511 and Y-415) on fatty acid and glucose metabolism in hepatocytes isolated
      from 24-h starved rats. During short-term exposure (1h) neither S-15261 nor its
      metabolites affected fatty acid oxidation whatever the concentration used. By
      contrast, S-15261 and its two metabolites reduced the rates of glucose production
      from lactate/pyruvate and dihydroxyacetone. Using crossover plot analysis, it was
      shown that Y-415 reduced hepatic gluconeogenesis upstream the formation of
      dihydroxyacetone phosphate. After 48 h in culture, S-15261 and its two
      metabolites reduced the rates of glucose production from lactate/pyruvate
      secondarily to a decrease in PEPCK and Glc-6-Pase mRNA levels. A part of these
      effects on gene expression could be due to a drug-induced reduction in PGC-1 gene
      expression. When hepatocytes were cultured in the presence of a submaximal
      concentration of insulin (10(-9)M), S-15261, through its metabolite S-15511,
      enhanced insulin sensitivity both on gene expression (PEPCK, Glc-6-Pase, PGC-1)
      and on gluconeogenesis. Furthermore, S-15261 and S-15511 induced the expression
      of GK and FAS genes as the result of an increased in SREBP-1c mRNA levels.
      Finally, S-15511 enhanced the stimulatory effect of insulin on GK mRNA level
      through an additional increase in SREBP-1c gene expression. In conclusion, this
      work reveals that S-15261 via its metabolites reduces hepatic glucose production
      through direct and insulin-sensitizing effects on genes encoding regulatory
      proteins of hepatic glucose metabolism.

PMID- 15993852
TI  - Role of Ca2+-independent phospholipase A2 and cytochrome P-450 in store-operated
      calcium entry in 3T6 fibroblasts.
AB  - Store-operated calcium (SOC) channels and capacitative Ca2+ entry play a key role
      in cellular functions, but their mechanism of activation remains unclear. Here,
      we show that thapsigargin induces [3H] arachidonic acid (AA) release, 45Ca2+
      influx and a subsequent enhancement of intracellular calcium concentration
      ([Ca2+]i. Thapsigargin-induced elevation of [Ca2+]i was inhibited by cytochrome P
      450 inhibitors and by cytochrome P-450 epoxygenase inhibitor and was reverted by
      11,12 EET addition. However, cyclooxygenase and lipoxygenase inhibitors have no
      effect. Moreover, we observed that four EETs were able to induce 45Ca2+ influx.
      Finally, we reported that the effect of 11,12 EET on 45Ca2+ influx was sensible
      to receptor-operated Ca2+ channel blockers (NiCl2, LaCl3) but not to voltage
      dependent Ca2+ channel blocker as verapamil. Thus, AA released by Ca2+
      independent phospholipase A2 and AA metabolism through cytochrome P-450 pathway
      may be crucial molecular determinant in thapsigargin activation of SOC channels
      and store-operated Ca2+ entry pathway in 3T6 fibroblasts. Moreover, EETs, the
      main cytochrome P-450 epoxygenase metabolites of AA, are involved in thapsigargin
      stimulated Ca2+ influx. In summary, our results suggest that EETs are components
      of calcium influx factor(s).

PMID- 15993853
TI  - Sequential induction of heme oxygenase-1 and manganese superoxide dismutase
      protects cultured astrocytes against nitric oxide.
AB  - Nitric oxide (NO) is a widely recognized mediator of physiological and
      pathophysiological signal transmission. In an attempt to better understand the
      molecular actions of NO in astrocytes, stress protein expression in response to
      NO donor sodium nitroprusside was investigated. Heme oxygenase-1 (HO-1) has been
      identified as an inducer of manganese superoxide dismutase (MnSOD), playing a
      cytoprotective role under the condition of nitrosative stress. We present
      evidence that the sequential induction of HO-1 and MnSOD protects astrocytes from
      NO toxicity: (1) both HO-1 and MnSOD expression were induced by NO; (2) NO
      mediated increase in MnSOD activity was partly abolished by HO-1 inhibitor Zn(II)
      protoporphyrin IX (ZnPP); (3) pretreatment of astrocytes with a nontoxic dose of
      NO protected the cells against the later treatment with a toxic dose of NO; (4)
      inhibition of HO-1 by ZnPP sensitized astrocytes to the nontoxic dose of NO
      resulting in a marked cytotoxicity; and (5) adenovirus-mediated overexpression of
      MnSOD protected astrocytes from the NO toxicity. The molecular action of NO in
      astrocytes appears to be dose-dependent. While a high dose of NO exerts
      cytotoxicity leading to the tissue damage in the central nervous system, a low
      dose of NO may act as an important signaling molecule in astrocytes with
      concurrent induction of cytoprotective proteins such as HO-1 and MnSOD.

PMID- 15993854
TI  - Association analysis of chromosome 5 GABAA receptor cluster in Japanese
      schizophrenia patients.
AB  - BACKGROUND: Several investigations suggest that abnormalities in gamma-amino
      butyric acid (GABA) neurotransmission systems may be related to the
      pathophysiology of schizophrenia. A GABA(A) receptor gene cluster on 5q31-35
      (beta2 [GABRB2], alpha6 [GABRA6], alpha1 [GABRA1], and gamma2 [GABRG2] subunit
      genes) is one of the most attractive candidate regions for schizophrenia
      susceptibility. METHODS: We performed 1) systematic polymorphism search of
      GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2)
      evaluation of linkage disequilibrium (LD) within this cluster with 35 single
      nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs";
      and 4) two-stage association analysis that comprised first-set screening analysis
      of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and
      second-set replication analysis of the positive htSNPs (901 schizophrenic
      patients and 806 control subjects). RESULTS: In the first-set scan, we found a
      significant association of two htSNPs in GABRA1, but no association of GABRB2,
      GABRA6, and GABRG2. In the following second-set analysis, however, we could not
      confirm these significant associations. CONCLUSIONS: These results indicate that
      this gene cluster may not play a major role in Japanese schizophrenia. They also
      raised an alert with regard to preliminary genetic association analysis using a
      small sample size.

PMID- 15993855
TI  - Sequence analysis of the serotonin transporter and associations with
      antidepressant response.
AB  - BACKGROUND: The serotonin transporter is the molecular target of many
      antidepressants, and the gene (SLC6A4) encoding this protein has been associated
      with response to selective serotonin reuptake inhibitors (SSRIs). We sought to
      test further the hypothesis that SLC6A4 is associated with SSRI response by
      resequencing this gene in subjects with major depression. METHODS: The sequence
      of all exons, parts of all introns, and the promoter region containing a
      polymorphic repeat polymorphism (HTTLPR) previously associated with SSRI response
      was determined for 96 subjects, and variants were tested for association to
      treatment response with fluoxetine. RESULTS: We screened a total of 712 kilobases
      of sequence and found 27 SLC6A4 variants, 21 of which were previously
      undescribed. Seventeen were seen on one chromosome each, including three of the
      five exonic variants. One polymorphism (rs25531), just upstream of the HTTLPR,
      showed evidence of an association with treatment response, and biochemical
      experiments showed this polymorphism altered binding of nuclear extracts to a
      consensus sequence for the activator protein 2 transcription factor, which is
      believed to be a critical factor in regulating neural gene expression in mammals.
      CONCLUSIONS: These results support an association between response to SSRIs and
      deoxyribonucleic acid variation at the serotonin transporter locus. We have also
      identified a potentially important functional variant that contributes to this
      association and a possible biologic mechanism that could mediate its effect.

PMID- 15993856
TI  - Cue-induced brain activity in pathological gamblers.
AB  - BACKGROUND: Previous studies using functional magnetic resonance imaging (fMRI)
      have identified differential brain activity in healthy subjects performing
      gambling tasks and in pathological gambling (PG) subjects when exposed to
      motivational and emotional predecessors for gambling as well as during gambling
      or response inhibition tasks. The goal of the present study was to determine if
      PG subjects exhibit differential brain activity when exposed to visual gambling
      cues. METHODS: Ten male DSM-IV-TR PG subjects and 10 matched healthy control
      subjects underwent fMRI during visual presentations of gambling-related video
      alternating with video of nature scenes. RESULTS: Pathological gambling subjects
      and control subjects exhibited overlap in areas of brain activity in response to
      the visual gambling cues; however, compared with control subjects, PG subjects
      exhibited significantly greater activity in the right dorsolateral prefrontal
      cortex (DLPFC), including the inferior and medial frontal gyri, the right
      parahippocampal gyrus, and left occipital cortex, including the fusiform gyrus.
      Pathological gambling subjects also reported a significant increase in mean
      craving for gambling after the study. Post hoc analyses revealed a dissociation
      in visual processing stream (dorsal vs. ventral) activation by subject group and
      cue type. CONCLUSIONS: These findings may represent a component of cue-induced
      craving for gambling or conditioned behavior that could underlie pathological
      gambling.

PMID- 15993858
TI  - Diagnosis-related regional gray matter loss over two years in first episode
      schizophrenia and bipolar disorder.
AB  - BACKGROUND: We examined gray- and white-matter brain volumes in first episode
      psychosis (FEP) at initial presentation and at two-year follow-up. We predicted
      that FEP subjects would show longitudinal reductions in fronto-temporal gray- and
      white-matter volumes compared with controls. Furthermore, we expected groups to
      be differentiated by diagnosis-related reductions. METHODS: Twenty-five
      schizophrenia and 8 bipolar disorder FEP patients underwent a structural MRI scan
      at first presentation and 2 years later. Matched healthy subjects (n = 22)
      underwent a single identical scan. RESULTS: At initial presentation FEP subjects
      had significantly less gray- and white-matter than healthy subjects. Diagnostic
      dissociations were revealed both at first presentation and at follow-up. In
      schizophrenia patients, gray-matter deficits were observed in lateral and medial
      frontal regions and in bilateral posterior temporal lobe regions, with additional
      extensive losses over time in lateral fronto-temporal regions and left anterior
      cingulate gyrus. By contrast, gray matter deficit in bipolar patients was
      localized to bilateral inferior temporal gyri with additional loss over time
      observed only in the anterior cingulate cortex. CONCLUSIONS: The results are
      consistent with a dual process model of psychosis, in which the diagnosis-related
      gray matter loss is determined by neurodevelopmental gray-matter volumetric
      differences which predate symptom onset, and diagnosis-related neurodegenerative
      gray-matter loss over time.

PMID- 15993857
TI  - Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an
      open-label trial.
AB  - BACKGROUND: Most patients with obsessive-compulsive disorder (OCD) show only
      partial reduction of symptoms with standard therapy. Recent imaging data suggests
      glutamatergic dysfunction in the corticostriatal pathway in OCD. We investigated
      the efficacy of augmentation therapy with riluzole, a glutamate-modulating agent,
      in treatment-resistant OCD. METHODS: Thirteen patients aged between 18 and 65
      years with a primary diagnosis of OCD that had proven resistant to standard
      treatment were treated with the addition of riluzole to their existing
      pharmacotherapy. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton
      Depression Inventory (HAM-D), and Hamilton Anxiety Inventory (HAM-A) scores were
      obtained weekly. RESULTS: Thirteen treatment-resistant OCD patients received
      riluzole 50 mg twice a day. Y-BOCS scores improved significantly over time. Of 13
      patients, 7 (54%) demonstrated a >35% reduction in Y-BOCS scores, and 5 (39%)
      were categorized as treatment responders. HAM-D and HAM-A scores for the group
      also significantly improved over time. Riluzole was well tolerated with no
      serious adverse effects noted. CONCLUSIONS: Riluzole appears to have significant
      antiobsessional, antidepressant, and antianxiety properties. The addition of this
      agent may be of practical clinical benefit in patients with OCD.

PMID- 15993859
TI  - A double dissociation of ventromedial prefrontal cortical responses to sad and
      happy stimuli in depressed and healthy individuals.
AB  - BACKGROUND: The ventromedial prefrontal cortex (VMPFC) is a region implicated in
      the assessment of the rewarding potential of stimuli and may be dysfunctional in
      major depressive disorder (MDD). The few studies examining prefrontal cortical
      responses to emotive stimuli in MDD have indicated increased VMPFC responses to
      pleasant images but decreased responses to sad mood provocation when compared
      with healthy individuals. We wished to corroborate these results by examining
      neural responses to personally relevant happy and sad stimuli in MDD and healthy
      individuals within the same paradigm. METHODS: Neural responses to happy and sad
      emotional stimuli (autobiographical memory prompts and congruent facial
      expressions) were measured using blood oxygenation level dependent (BOLD)
      functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12)
      individuals. RESULTS: Increased and decreased responses in VMPFC were observed in
      MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern
      was reversed for MDD and healthy individual responses to sad stimuli. These
      findings were not explained by medication effects in depressed individuals.
      CONCLUSIONS: These findings indicate a double dissociation of the pattern of
      VMPFC response to happy and sad stimuli in depressed and healthy individuals and
      suggest abnormal reward processing in MDD.

PMID- 15993860
TI  - A randomized trial of citalopram versus placebo in outpatients with asthma and
      major depressive disorder: a proof of concept study.
AB  - BACKGROUND: The prevalence of asthma has increased in recent years and depression
      is common in this population. Minimal data are available on the treatment of
      depressed asthma patients. METHODS: Ninety adults with asthma and current major
      depressive disorder were randomized to receive citalopram or placebo for 12
      weeks. At each visit, the Hamilton Rating Scale for Depression (HRSD), Inventory
      of Depressive Symptomatology - Self-Report, Asthma Control Questionnaire, and
      Asthma Quality of Life Questionnaire were administered, and oral corticosteroid
      use assessed. RESULTS: In the evaluable sample (n = 82), the primary outcome, a
      random regression analysis of HRSD scores, revealed no significant between-group
      differences. Bonferroni corrected secondary outcomes revealed HRSD scores
      decreased significantly in both groups with a significantly greater decrease in
      the citalopram group at week 6. Changes in asthma symptoms were similar between
      groups. The groups had similar rates of oral corticosteroid use at baseline, but
      the citalopram group had less corticosteroid use during the study. Changes in
      asthma symptom severity correlated with changes in depressive symptom severity.
      CONCLUSIONS: A reduction in depressive symptoms was associated with improvement
      in asthma. Corticosteroid use, an important measure of severe asthma
      exacerbations, was lower in the citalopram group. Larger clinical trials in this
      population are warranted.

PMID- 15993861
TI  - Reduced anterior and posterior cingulate gray matter in borderline personality
      disorder.
AB  - BACKGROUND: Structural abnormalities in prefrontal and cingulate gyrus regions
      important in affective processing, impulse control and cognition may contribute
      to the psychopathology of borderline personality disorder (BPD). Previous MRI
      studies examining volume have reported that compared with healthy controls, BPD
      patients have decreases in right anterior cingulate, no differences in
      dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We
      extended this investigation by examining gray and white matter volume of frontal
      and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy
      controls. METHODS: MRI scans were acquired in 50 BPD patients (n = 13 with
      comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37
      without SPD) and 50 healthy controls, and gray/white matter volume in cingulate
      gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons
      were conducted. RESULTS: Compared with controls, BPD patients showed reduced gray
      matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD
      had isolated gray matter volume loss in BA 24, but were spared for BA 31 in
      contrast to BPD patients with SPD. There were no group differences in whole
      cingulate or frontal lobe volume. CONCLUSIONS: The finding of more pervasive
      cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent
      observations with the same methods in patients with schizophrenia. The pattern of
      reduced anterior and posterior cingulate gray matter volume in BPD patients,
      particularly those comorbid for SPD is consistent with the affective and
      attentional deficits observed in these personality disorders.

PMID- 15993863
TI  - Inhibition of medullary raphe/parapyramidal neurons prevents cutaneous
      vasoconstriction elicited by alerting stimuli and by cold exposure in conscious
      rabbits.
AB  - In conscious rabbits, microinjection of muscimol into the medullary
      raphe/parapyramidal region decreased fluctuation (coefficient variation) of
      resting ear blood flow (from 62 +/- 8 to 25 +/- 4%, P < 0.01, n = 8). The
      muscimol injection also prevented falls in ear blood flow that normally occur in
      response to alerting stimuli and to cold exposure. Thus, raphe/parapyramidal
      neurons constitute an important brainstem center for mediating cutaneous
      vasoconstriction initiated by alerting stimuli and by cold exposure.

PMID- 15993862
TI  - Expression of c-fos and BDNF mRNA in subregions of the prefrontal cortex of male
      and female rats after acute uncontrollable stress.
AB  - Women exhibit higher lifetime prevalences of stress-related disorders than men.
      These disorders have been associated with changes in prefrontal cortex structure
      and function. Here, we examine the effects of acute inescapable stress, an animal
      model of behavioral depression and post-traumatic stress disorder, on plasma
      corticosterone (CORT) and on c-fos mRNA and brain-derived neurotrophic factor
      (BDNF) mRNA in regions of the prefrontal and frontal cortex in male and cycling
      female rats. Inescapable stress consisted of 100 1 mA tailshocks, and no-stress
      controls remained in their home cages. Rats were sacrificed immediately (0 min)
      or 60 min after termination of the stressor. CORT levels were increased at both 0
      and 60 min post-stress termination relative to controls, and the increase was
      greater in females at both time points. c-fos mRNA expression increased at 0 min
      in prefrontal cortical regions, but this increase was greater in males than
      estrus and proestrus females. At 60 min, c-fos mRNA levels were lower than at 0
      min in males but not females. No correlations between CORT and c-fos mRNA levels
      in prefrontal regions were observed in females in the stress groups, but
      significant correlations were observed in males in several prefrontal regions.
      BDNF mRNA expression was greater in control females than control males.
      Inescapable stress increased BDNF mRNA expression at 0 but not 60 min in males,
      but there was no effect of inescapable stress on BDNF mRNA in females. These
      results reveal sex differences in inescapable stress-induced gene expression that
      may have implications for differences in vulnerability to stress-related
      disorders.

PMID- 15993864
TI  - Glutamate receptor antagonists and growth factors modulate dentate granule cell
      neurogenesis in organotypic, rat hippocampal slice cultures.
AB  - Generation of dentate granule cells and its modulation by glutamate receptor
      antagonists, growth factors and pilocarpine-induced seizure-like activity was
      investigated in rat hippocampal slice cultures derived from 1-week-old rats and
      grown for 2 weeks. Focussing on the dentate granule cell layer facing CA1 and the
      immediate subgranular zone, exposure for 3 days to the NMDA receptor blocking
      agents MK-801 (10 microM) or APV (25 microM) in the culture medium, increased the
      number of TOAD-64/Ulip/CRMP-4 (TUC-4)-positive cells as counted in the slice
      cultures at the end of the 3-day treatment period. Exposure to IGF-I (200 ng/ml)
      and EGF (20 ng/ml) also increased the number of TUC-4-positive cells. Combining
      APV with IGF-I/EGF had an additive effect. Similar results were obtained by 3
      days treatment with the AMPA receptor antagonist CNQX (25 microM). Surprisingly,
      addition of 5 mM pilocarpine reduced the number of TUC-4-positive cells, just as
      combining pilocarpine with the neurogenesis-stimulating compounds, prevented or
      reduced the increase of TUC-4-positive cells. None of the treatments were found
      to induce dentate granule cell death within the observed period. Labeling of
      dividing cells by adding 5-bromo-2-deoxyuridine (BrdU) to the culture medium did
      not result in cells double-labeled with BrdU and TUC-4. The induced increase in
      TUC-4-positive cells therefore represent neuronal differentiation of existing
      neural precursor cells when investigated at the 3-day time point. We conclude
      that 3 days treatment of 2-week-old hippocampal slice cultures with IGF-I and EGF
      and NMDA and AMPA glutamate receptor antagonists increase granule cell
      neurogenesis from preexisting neural precursors.

PMID- 15993865
TI  - The effect of carbamazepine on injury-induced ectopic discharge in the lingual
      nerve.
AB  - Previous studies have shown that the development of ectopic activity from damaged
      axons following nerve injury may contribute to the aetiology of sensory
      disturbances, including dysaesthesia. Pharmacological manipulation of this
      activity could provide a method of treatment for this intractable condition. In
      this study we have investigated the effect of carbamazepine, an anti-convulsant,
      as it is known to have membrane stabilising properties. In eight anaesthetised
      adult ferrets the left lingual nerve was sectioned and the animals allowed to
      recover for 3 days. Then, in terminal experiments under general anaesthesia, the
      nerve was re-exposed and electrophysiological recordings were made from
      spontaneously active units in fine filaments dissected from the nerve proximal to
      the injury site. Carbamazepine in a modified cyclodextrin (hydroxypropyl-beta
      cyclodextrin) was administered intravenously in increments, in order to achieve a
      progressively increasing systemic concentration, and serum levels were determined
      at the point that activity ceased. Twenty-one spontaneously active units were
      studied, with conduction velocities of 2.1-28.9 m s(-1) and discharge frequencies
      of 0.25-15.3 Hz. Spontaneous activity ceased in 13 units with a serum
      concentration of carbamazepine ranging from 3.5 to 8.4 mg/l, which was within the
      normal therapeutic range (4-12 mg/l). Four units ceased activity with
      carbamazepine levels above the therapeutic range (15.4-17.2 mg/ml), but the
      remaining four continued to discharge throughout the recording period. These data
      suggest that systemic carbamazepine can reduce the level of spontaneous activity
      initiated in some axons following lingual nerve injury.

PMID- 15993866
TI  - AFM studies of water-soluble wheat arabinoxylans--effects of esterase treatment.
AB  - The degradation products of water-soluble wheat arabinoxylans treated with
      Aspergillus niger ferulic acid esterase (FAEA-able to cleave 5,5'- and 8-O-4'
      ferulic acid dimers) have been characterised by atomic force microscopy (AFM) and
      size exclusion chromatography. The AFM images of arabinoxylans confirmed that a
      small proportion ( approximately 15%) of the population of arabinoxylan molecules
      contain xylan-based branches attached to the xylan-based backbone. Treatment with
      FAEA reduced the contour length of the molecules suggesting that certain dimeric
      ferulic acid linkages may play a previously unconfirmed role in the elongation of
      arabinoxylans. Overnight treatment with FAEA led to a reduction in the density of
      branches suggesting that they may also be linked to the backbone through phenolic
      linkages.

PMID- 15993867
TI  - N-Acyl derivatives of glucosamine as acceptor substrates for
      galactosyltransferase from bone and cartilage cells.
AB  - Glucosamine is commonly used as a nutraceutical by arthritis patients. However,
      its mode of action is still unknown, and there is controversy about its clinical
      efficacy. Synthetic N-acyl glucosamines (acyl group>2 carbons) comprise a new
      class of drugs. We examined these derivatives for their effect in bone and
      cartilage cells, and for their ability to serve as acceptor substrates for
      galactosyltransferase. With the exception of N-benzoylglucosamine, compounds of
      the series were good substrates for galactosyltransferases from bone and
      cartilage cells, and for purified enzyme from bovine milk. When N
      butyrylglucosamine (GlcNBu) was added to the cell medium of primary bovine
      chondrocytes and human osteoblasts, small amounts were found to enter the cells
      and a radiolabeled metabolite appeared in the medium. However, GlcNBu did not
      appear to be incorporated directly into oligosaccharides. GlcNBu at 1 and 5mM
      concentrations in the glucose-free cell medium of primary human osteoblasts from
      osteoarthritis patients did not significantly alter cell proliferation or cell
      differentiation.

PMID- 15993868
TI  - Regioselective phosphorylation of branched cyclodextrins with cyclo-mono-mu
      imidotriphosphate.
AB  - The phosphorylation of the branched cyclodextrins, mono-6-O-(alpha-D
      glucopyranosyl)cyclomaltohexaose, mono-6-O-(alpha-D-maltosyl)cyclomaltohexaose,
      mono-6-O-(alpha-D-glucopyranosyl)cyclomaltoheptaose, and mono-6-O-(alpha-D
      maltosyl)cyclomaltoheptaose, in aqueous solution by sodium cyclo-mono-mu
      imidotriphosphate (cMITP) was examined. In these reactions, only the 2-OH group
      of a single alpha-D-glucopyranosyl residue of the cyclodextrin ring was
      phosphorylated, in a maximum yield of 67%. A possible mechanism for the
      phosphorylation is discussed.

PMID- 15993869
TI  - Hypoxic modulation of cardiac L-type Ca2+ current: interaction of reactive oxygen
      species and beta-adrenergic signaling.

PMID- 15993870
TI  - Cytochrome P450 and arachidonic acid metabolites: role in myocardial
      ischemia/reperfusion injury revisited.
AB  - Ischemia-reperfusion of the heart and other organs results in the accumulation of
      unesterified arachidonic acid (AA) via the action of membrane-bound
      phospholipases, primarily phospholipase A2. AA can be metabolized by the
      classical cyclooxygenase (COX) and lipoxygenase (LOX) pathways to well
      characterized metabolites and their respective cardioprotective end products such
      as prostacyclin (PGI2) and 12-hydroxyeicosatetraenoic acid (12-HETE). However, it
      has only been recently recognized that another less well-characterized pathway of
      AA metabolism, the cytochrome P450 (CYP) pathway, may have important
      cardiovascular effects. Several lines of data support the possibility that
      certain CYP metabolites resulting from the hydroxylation of AA such as 20
      hydroxyeicosatetraenoic acid (20-HETE) are potent vasoconstrictors and may
      produce detrimental effects in the heart during ischemia and pro-inflammatory
      effects during reperfusion. On the other hand, a group of regioisomers resulting
      from the epoxidation of AA, including 5,6-, 8,9-, 11,12- and 14,15
      epoxyeicosatrienoic acid (EETs), have been shown to reduce ischemic and/or
      reperfusion injury in the heart and vasculature. This review will discuss the
      detrimental and beneficial actions, including the potential cellular mechanisms
      responsible as a result of stimulating or inhibiting the two arms of this novel
      CYP pathway. The therapeutic potential of increasing EET concentrations and/or
      reducing 20-HETE concentrations will also be addressed.

PMID- 15993871
TI  - Does peroxynitrite sustain nuclear factor-kappaB?

PMID- 15993872
TI  - Blood outgrowth endothelial cells from Hereditary Haemorrhagic Telangiectasia
      patients reveal abnormalities compatible with vascular lesions.
AB  - OBJECTIVE: Hereditary haemorrhagic telangiectasia (HHT) is originated by
      mutations in endoglin (HHT1) and ALK1 (HHT2) genes. The purpose of this work was
      to isolate and characterize circulating endothelial cells from HHT patients.
      METHODS: Pure primary cultures of blood outgrowth endothelial cells (BOECs) were
      obtained from 50 ml of peripheral blood by selection on collagen plates with
      endothelial medium. RESULTS: The amount of endoglin in HHT1-BOECs is half the
      controls, but HHT2-BOECs are also endoglin-deficient. Since the TGF-beta/ALK1
      pathway activates the endoglin promoter activity, these results suggest the
      involvement of ALK1 in endoglin gene expression. Endothelial TGF-beta pathways,
      mediated by ALK1 and ALK5, are impaired in HHT cells. HHT-BOECs show disorganized
      and depolymerized actin fibers, as compared to the organized stress fibers of
      healthy-BOECs. Functionally, HHT-BOECs have impaired tube formation, in contrast
      with the cord-like structures derived from normal donors. CONCLUSIONS: Decreased
      endoglin expression, impaired TGF-beta signalling, disorganized cytoskeleton, and
      failure to form cord-like structures are common characteristics of endothelial
      cells from HHT patients. These features may lead to fragility of small vessels
      and bleeding characteristic of the HHT vascular dysplasia and to a disrupted and
      abnormal angiogenesis, which may explain the clinical symptoms associated with
      this disease.

PMID- 15993873
TI  - Genetic association of paraoxonase-1 polymorphisms and chronic hepatitis C virus
      infection.
AB  - BACKGROUND: Hepatitis C virus infection is associated with hepatic free radical
      formation and enhanced lipid peroxidation and an individual's antioxidant status
      may play an important role. Paraoxonase-1 is an esterase that degrades oxidised
      lipids. In the present study, we investigated the genetic association of the most
      important paraoxonase-1 gene polymorphisms and the susceptibility to HCV-related
      chronic hepatitis. METHODS: Paraoxonase-1 polymorphisms at positions -107, 55 and
      192 were analysed from the genomic DNA of 186 patients and 386 healthy
      volunteers, as well as the serum concentration of total peroxides and standard
      biochemical tests. RESULTS: Patients with chronic hepatitis had a higher
      frequency of the RR isoform of the 192 polymorphism than healthy subjects (13%
      vs. 7%, P<0.05). There were no significant differences with respect to the -107
      and 55 polymorphisms. The plasma concentration of peroxides was higher in
      patients with chronic hepatitis [349.5 (246.2-479.8) vs. 115.4 (95.7-172.3)
      mumol/L; P<0.001]. CONCLUSIONS: The present study suggests that the paraoxonase-1
      192 polymorphism contributes, together with other polymorphisms, to the
      variations in the host response to HCV infection.

PMID- 15993874
TI  - Molecular analysis of homocystinuria in Brazilian patients.
AB  - BACKGROUND: Cystathionine beta-synthase (CBS) deficiency is the most common cause
      of homocystinuria. However, no data are available concerning the molecular basis
      of this disease in Brazilian populations. METHODS: We studied 14 Brazilian
      patients from 11 unrelated families using a combined screening approach,
      involving restriction analysis, single-strand conformational polymorphism (SSCP)
      scanning, and sequencing. RESULTS: All patients presented homocysteine levels
      higher than 200 mumol/l before the beginning of treatment. The most common CBS
      gene mutations, p.G307S (c.919G > A) and p.I278T (c.833T > C), were evaluated and
      the allele c.919A was not found. One allele with the c.844 ins68 (4.5%) in the
      CBS gene was found. Three families (6 patients) presented the allele c.833 C
      (13.6%), without the insertion in the heterozygous state. SSCP scanning and
      sequencing showed 3 alleles p.T191M (13.64%) in 2 families. One allele with a
      novel mutation was found in exon 4 (c.168T > A) of the CBS gene (4.5%). We also
      analyzed c.677C > T and c.1298A > C polymorphisms in the
      methylenetetrahydrofolate reductase (MTHFR) gene and the 2756A > G polymorphism
      in the methionine synthase (MTR) gene. The frequencies of mutated alleles were:
      50% c.677T and 18.2% c.1298C for MTHFR, and 27.3% c.2756G for MTR. CONCLUSION: In
      spite of the high level of racial mixing in the country, Brazilian homocystinuric
      patients did not present a high prevalence of the most common mutations described
      in the literature.

PMID- 15993875
TI  - Correlation of acid alpha-glucosidase and glycogen content in skin fibroblasts
      with age of onset in Pompe disease.
AB  - BACKGROUND: Pompe disease is an autosomal recessive disorder of glycogen
      metabolism resulting from a deficiency of acid alpha-glucosidase. Pompe disease
      can present within a broad clinical spectrum, from the severe infantile to the
      attenuated adult onset phenotypes. Early diagnosis, in the form of newborn
      screening has been proposed. However, in the absence of clinical symptoms,
      prediction of disease severity and progression will be critical to provide
      appropriate management and treatment of affected individuals. METHODS: We have
      used sensitive immune-assays to measure levels of acid alpha-glucosidase protein
      and activity in cultured skin fibroblasts and a new glycogen assay to
      specifically determine the lysosomal accumulation of glycogen in the same cells.
      These markers were assessed for their ability to predict age of onset. RESULTS:
      Acid alpha-glucosidase activity and specific activity as well as lysosomal
      glycogen showed significant correlations with age of onset, with acid alpha
      glucosidase activity having the highest Spearman correlation coefficient (0.887,
      p<0.001). Lysosomal glycogen accumulated only in cells from infantile and
      juvenile patients but not from adult-onset patients. However, cells from adult
      onset patients had relatively low cytoplasmic glycogen compared to control
      individuals and other forms of the disease. CONCLUSION: Acid-alpha-glucosidase
      activity and specific activity, and lysosomal glycogen content are useful
      predictors of age of onset in Pompe disease.

PMID- 15993876
TI  - Association of the risk allele of dopamine transporter gene (DAT1*10) in Omani
      male children with attention-deficit hyperactivity disorder.
AB  - OBJECTIVES: To determine the frequency of the VNTR alleles in the human dopamine
      transporter gene (DAT1) in the Omani population and to investigate association of
      the VNTR alleles with attention-deficit hyperactivity disorder (ADHD). DESIGN AND
      METHODS: 92 Omani children with ADHD and 110 healthy Omani subjects were
      genotyped for the DAT1-VNTR polymorphism in a case-control study using two
      independent PCR tests (one developed in our laboratory) followed by agarose gel
      electrophoresis. RESULTS AND CONCLUSIONS: We determined the DAT1-VNTR alleles in
      202 Omani subjects. There were two common alleles (DAT1*9 and *10) and five rare
      ones. The DAT1*10 allele distribution was essentially the same both in the
      control (60.9%) and the patient group (64.6%). There was, however, a relatively
      higher occurrence of the DAT1*10 allele in ADHD males (69.4%) than females (55%),
      but this gender difference was not present in the control group (males 60%,
      females 62%).

PMID- 15993877
TI  - The fluidity of Chinese hamster ovary cell and bull sperm membranes after
      cholesterol addition.
AB  - Cell plasma membrane fluidity is affected by membrane lipid and protein
      composition as well as temperature. Altering the cholesterol content of a
      membrane can change membrane fluidity at different temperatures and this may
      affect cell survival during cryopreservation. In these experiments, we examined
      the effect that adding cholesterol to the membranes of Chinese hamster ovary
      cells (CHO) and bull sperm had on cell plasma membrane fluidity and cell survival
      when cells were cooled to 5 degrees C or were cryopreserved. Cells were treated
      with 0, 1.5 or 5.0mg cholesterol-loaded cyclodextrin (CLC), stained with N-((4-(6
      phenyl-1,3,5-hexatrienyl)phenyl)propyl)trimethylammonium-p-toluenesulfonate (TMAP
      DPH) to evaluate membrane fluidity and with propidium iodide to evaluate cell
      viability, prior to analysis by flow cytometry at 23, 5 degrees C, and after
      cryopreservation. CHO cells exhibited a single cell population with all cells
      having similar membrane fluidity. Membrane fluidity did not change when
      temperature had been reduced and then returned to 23 degrees C (P<0.05), however,
      adding cholesterol to the cells induced membranes to become more rigid (P<0.05).
      Bull sperm samples consisted of two cell subpopulations, one having relatively
      higher membrane fluidity than the other, regardless of cholesterol treatment or
      temperature. In addition, cells possessing the highest membrane fluidity did not
      survive cooling or cryopreservation efficiently. CLC treatment did not
      significantly alter membrane fluidity after temperature changes, but did maintain
      higher percentages of spermatozoa surviving cooling to 5 degrees C and
      cryopreservation (P<0.05). In conclusion, adding cholesterol to cell resulted in
      detectable membrane fluidity changes in CHO cells and increased survival of bull
      sperm after cooling to 5 degrees C and after cryopreservation.

PMID- 15993878
TI  - Altered primordial germ cell migration in the absence of transforming growth
      factor beta signaling via ALK5.
AB  - Transforming growth factor beta (TGFbeta) inhibits proliferation and promotes the
      migration of primordial germ cells (PGCs) towards explants of gonadal ridges in
      vitro. However, its effects in vivo are still unclear. Here, we analyzed the
      behavior of PGCs in embryos lacking TGFbeta signaling via the type I receptor
      ALK5. TGFbeta in vivo was neither a chemoattractant for PGCs, nor did it affect
      their proliferation during migration towards the gonadal ridges up to embryonic
      day (E)10. Unexpectedly, the absence of TGFbeta signaling in fact resulted in
      significant facilitation of PGC migration out of the hindgut, due to the reduced
      deposition of collagen type I surrounding the gut of Alk5-deficient mutant
      embryos. Migratory PGCs adhere strongly to collagen; therefore, reduced collagen
      type I along the gut may result in reduced adhesion, facilitating migration into
      the dorsal mesenterium and gonadal ridges. Our results provide new evidence for
      the role of TGFbeta signaling in migration of PGCs in vivo distinct from that
      described previously.

PMID- 15993879
TI  - Effect of prostaglandin I2 analogues on left ventricular diastolic function in
      vivo.
AB  - The prostaglandin I2 analogues epoprostenol and iloprost increase left
      ventricular contractility. Therefore, we hypothesize that the prostaglandin I2
      analogues epoprostenol and iloprost improve also left ventricular diastolic
      function. To test this hypothesis, the effects of epoprostenol and iloprost on
      left ventricular diastolic function were assessed in vivo and compared to two
      vasodilators sodium nitroprusside and adenosine, not formerly associated with
      changes of left ventricular contractility. Eleven pigs (25.9+/-2.8 kg, balanced
      anaesthesia) were exposed to the short-acting intravenous vasodilators sodium
      nitroprusside, adenosine and epoprostenol in a randomized cross over design. The
      long-acting iloprost was administered at the end of the protocol. The drugs are
      titrated to achieve a 25% reduction of diastolic aortic pressure. Active
      isovolumic relaxation properties of the left ventricle were assessed by the
      maximum velocity of left ventricular pressure drop. Passive phase of relaxation
      and filling was assessed by the determination of end diastolic compliance during
      a preload reduction manoeuvre. The maximum velocity of left ventricular pressure
      drop worsened during the infusion of sodium nitroprusside (baseline: -1950;
      sodium nitroprusside: -1293 mm Hg/s, p<0.05, Wilcoxon signed rank test versus vs.
      baseline) and adenosine (baseline: -2015; adenosine: -1345 mm Hg/s, p<0.05), but
      remained stable during the infusion of the prostaglandins (baseline: -1943;
      epoprostenol: -1785 mm Hg/s; baseline: -2042; iloprost: -1923 mm Hg/s). End
      diastolic compliance was not altered significantly by any vasodilator.
      Interstitial myocardial cAMP increased during the infusion of epoprostenol (7.60
      to 13.87 fmol/ml, p<0.05) and tended to increase during the infusion of iloprost
      (7.56 to 11.66 fmol/ml, p=0.21). The prostaglandin I(2) analogues epoprostenol
      and iloprost preserved the early phase of active isovolumic relaxation,
      presumably mediated by myocardial cAMP, whereas sodium nitroprusside and
      adenosine impaired early active isovolumic relaxation. Passive relaxation and
      filling properties remained stable during the infusion of each applied
      vasodilator in the intact left ventricle in vivo.

PMID- 15993880
TI  - Distribution of paraoxonase PON1 gene polymorphisms in Mexican populations. Its
      role in the lipid profile.
AB  - Paraoxonase gene polymorphisms (PON1-55 and PON1-192) were determined in four
      Mexican populations (Mestizos, Nahuas, Teenek and Mayos) belonging to different
      ethnic groups. The role of these polymorphisms in the lipid profile in the
      Mestizo group was also analyzed. PON1 polymorphisms were determined by polymerase
      chain reaction-restriction fragment length polymorphism. Comparison among Mexican
      populations showed increased frequencies of PON1-55 L allele and LL genotype and
      decreased frequencies of M allele and LM genotype in the three Amerindian
      populations when compared to Mestizos (P < 0.05). Mexicans together with Asian
      populations (from Japan and China) presented the highest frequencies of PON1-55 L
      allele (P < 0.05 when compared to Caucasian populations). Heterogeneous data were
      noted when PON1-192 polymorphism comparison was made. In summary, distribution
      frequencies of PON1 showed that Mexican populations are more related to Asians
      than Caucasians. This confirms previous studies with other genetic markers
      indicating that Native Americans have stronger genetic affinities to the
      Paleolithic people of North-East Asia than to other major world populations. In
      Mexican Mestizos, lack of correlation between PON1 polymorphisms and lipid
      profile was found, corroborating previous data in other populations. The present
      data could be helpful to understand the distribution of these polymorphisms and
      its role as genetic and evolutive markers in the Amerindian populations.

PMID- 15993881
TI  - IgG antibodies with peroxidase-like activity from the sera of healthy Wistar
      rats.
AB  - Various catalytic antibodies or abzymes (Abzs) have been detected recently in the
      sera of patients and animals with many autoimmune diseases, where their presence
      is most probably associated with autoimmunization. Normal humans or animals
      usually do not contain Abzs. In contrast, polyclonal Abzs from healthy humans and
      animals have an intrinsic superoxide dismutase activity and catalyze formation of
      H(2)O(2) (Wentworth et al., 2000, Proc. Natl. Acad. Sci. USA; 2001, Science).
      Here, we present the first evidence showing that highly purified native IgGs from
      the sera of healthy Wistar rats interact with H(2)O(2) and possess peroxidase
      like activity. Specific peroxidase activity of IgG preparations from the sera of
      10 rats varied in the range 1.6-27% as compared with that for horseradish
      peroxidase (100%). Antioxidant enzymes such as superoxide dismutases, catalases,
      and glutathione peroxidases are known to represent critical defence mechanisms
      for preventing oxidative modifications of DNA, proteins, and lipids. Antioxidant
      peroxidase activity of Abzs can also play an important role in the protection of
      organisms from oxidative stress as well as in oxidation of toxic compounds.

PMID- 15993882
TI  - An experimental model of reproducible liver trauma.
AB  - The aim of the study was to create an experimental model of reproducible and
      controllable liver trauma in pigs. The few reported experimental models of liver
      trauma use the "clamp and crush" mechanism of injury and do not cause
      reproducible liver injury. In the present study, force was applied through the
      thoracic wall to mimic a chest injury. Nine pigs were used as experimental
      animals. In anaesthetised animals, blunt liver trauma was caused with a crossbow
      using an arrow with a spherical aluminium head as a projectile. Liver injuries of
      stages II to III according to liver injury scale were inflicted on all the
      animals. The stage of liver trauma was proportional to the pressure impulse
      (ratio between the product of the arrow's mass (m) and the velocity (v) and the
      contact surface area of the arrow (S)). The presented model of controllable liver
      injury will enable the study of various aspects of liver trauma since the
      experiment can be designed in such a way to produce a spectrum of liver injuries.

PMID- 15993883
TI  - New genotypes and factors associated with Cryptosporidium detection in mussels
      (Mytilus spp.) along the California coast.
AB  - A 3 year study was conducted to evaluate mussels as bioindicators of faecal
      contamination in coastal ecosystems of California. Haemolymph samples from 4680
      mussels (Mytilus spp.) were tested for Cryptosporidium genotypes using PCR
      amplification and DNA sequence analysis. Our hypotheses were that mussels
      collected from sites near livestock runoff or human sewage outflow would be more
      likely to contain the faecal pathogen Cryptosporidium than mussels collected
      distant to these sites, and that the prevalence would be greatest during the wet
      season when runoff into the nearshore marine environment was highest. To test
      these hypotheses, 156 batches of sentinel mussels were collected quarterly at
      nearshore marine sites considered at higher risk for exposure to livestock
      runoff, higher risk for exposure to human sewage, or lower risk for exposure to
      both faecal sources. Cryptosporidium genotypes detected in Haemolymph samples
      from individual mussels included Cryptosporidium parvum, Cryptosporidium felis,
      Cryptosporidium andersoni, and two novel Cryptosporidium spp. Factors
      significantly associated with detection of Cryptosporidium spp. in mussel batches
      were exposure to freshwater outflow and mussel collection within a week following
      a precipitation event. Detection of Cryptosporidium spp. was not associated with
      higher or lower risk status for exposure to livestock faeces or human sewage
      sources. This study showed that mussels can be used to monitor water quality in
      California and suggests that humans and animals ingesting faecal-contaminated
      water and shellfish may be exposed to both host-specific and anthropozoonotic
      Cryptosporidium genotypes of public health significance.

PMID- 15993885
TI  - Sex differences in the relation of body composition to markers of inflammation.
AB  - OBJECTIVE: It has been suggested that low-grade systemic inflammation is
      associated with obesity and that this association might be modified by sex.
      METHODS AND RESULTS: We performed a cross-sectional analysis among 641 men and
      597 women aged 55-74 years who participated in the population-based KORA Survey
      2000, conducted in the area of Augsburg, Germany. Measures of both total (fat
      mass, body mass index) and abdominal adiposity (waist circumference (WC), waist
      to hip ratio (WHR)) were highly correlated with markers of systemic inflammation
      (C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen (FIB), interleukin-6
      (IL-6)) in men and in women. Significant associations persisted when the effect
      of lifestyle factors was taken into account. In multivariable linear regression
      analysis, a considerably higher percentage of variability in inflammatory markers
      was explained by body composition in women compared to men. Furthermore, the
      relevance of single body composition variables varied by sex. In women, fat mass
      in % explained the highest percentage of the variability of circulating acute
      phase proteins (18.2% for CRP, 7.2% for SAA, 6.1% for FIB, all p-values < 0.001),
      whereas in men, WHR explained the highest percentage of the variability (6.2% for
      CRP, 2.3% for SAA, 1.8% for FIB, all p-values < 0.001). For IL-6, WC explained
      the highest percentage of the variability in women (3.7%, p < 0.001) and in men
      (1.8%, p < 0.001). CONCLUSION: Adiposity is strongly associated with low-grade
      systemic inflammation in men and in women but the association is considerably
      stronger in women, especially for CRP. Thus, weight reduction as a means to
      prevent a state of subclinical inflammation might be particularly effective in
      women.

PMID- 15993884
TI  - Major role of HSP70 as a paracrine inducer of cytokine production in human
      oxidized LDL treated macrophages.
AB  - Lipid accumulation and inflammation are key hallmarks of the atherosclerotic
      plaque and macrophage uptake of oxidized low-density lipoprotein (oxLDL) is
      believed to drive these processes. Initial experiments show that supernatants
      from oxLDL treated macrophages could induce IL-1beta production in naive
      macrophages. To search for potential paracrine mediators that could mediate this
      effect a DNA microarray scan of oxLDL treated human macrophages was performed.
      This analysis revealed that oxLDL induced activation of heat shock protein (HSP)
      expression. HSPs have been implicated in the development of atherosclerosis, but
      the exact mechanisms for this is unclear. Extracellular heat shock protein 70
      (HSP70) has been shown to elicit a pro-inflammatory cytokine response in
      monocytes and could therefore be a potential paracrine pro-inflammatory mediator.
      After 24 h of oxLDL treatment there was a significant increase of HSP70
      concentrations in supernatants from oxLDL treated macrophages (oxLDLsup) compared
      to untreated controls (P<0.05). OxLDLsup could induce both interleukin (IL)-1beta
      and IL-12 secretion in naive macrophages. We also demonstrate that the effect of
      oxLDLsup on cytokine production and release could be blocked by inhibition of
      HSP70 transcription or secretion or by the use of HSP70 neutralizing antibodies.
      This suggests that extracellular HSP70 can mediate pro-inflammatory changes in
      macrophages in response to oxLDL.

PMID- 15993886
TI  - Effect of different ankle- and knee-joint positions on gastrocnemius medialis
      fascicle length and EMG activity during isometric plantar flexion.
AB  - The purpose of this study was to provide evidence on the fact that the observed
      decrease in EMG activity of the gastrocnemius medialis (GM) at pronounced knee
      flexed positions is not only due to GM insufficiency, by examining muscle
      fascicle lengths during maximal voluntary contractions at different positions.
      Twenty-two male long distance runners (body mass: 78.5+/-6.7 kg, height: 183+/-6
      cm) participated in the study. The subjects performed isometric maximal voluntary
      plantar flexion contractions (MVC) of their left leg at six ankle-knee angle
      combinations. To examine the resultant ankle joint moments the kinematics of the
      left leg were recorded using a Vicon 624 system with 8 cameras operating at 120
      Hz. The EMG activity of GM, gastrocnemius lateralis (GL), soleus (SOL) and
      tibialis anterior (TA) were measured using surface electromyography.
      Synchronously, fascicle length and pennation angle values of the GM were obtained
      at rest and at the plateau of the maximal plantar flexion using ultrasonography.
      The main findings were: (a) identifiable differences in fascicle length of the GM
      at rest do not necessarily imply that these differences would also exist during a
      maximal isometric plantar flexion contraction and (b) the EMG activity of the
      biarticular GM during the MVC decreased at a pronounced flexed knee-joint
      position (up to 110 degrees ) despite of no differences in GM fascicle length. It
      is suggested that the decrease in EMG activity of the GM at pronounced knee
      flexed positions is due to a critical force-length potential of all three muscles
      of the triceps surae.

PMID- 15993887
TI  - Low-temperature ionic liquids immobilized in porous alumina.
AB  - The pores in an aluminum oxide matrix can be completely filled with 1-alkyl-3
      methylimidazolium tetrafluoroborates, hexafluorophosphates, triflates, and
      bis(trifluoromethylsulfonyl)imides. This possibility can be utilized to produce
      solid electrolytes for batteries and fuel cells.

PMID- 15993888
TI  - Monodisperse DNA restriction fragments II. Sedimentation velocity and equilibrium
      experiments.
AB  - We report sedimentation velocity and equilibrium measurements performed with an
      analytical ultracentrifuge to elucidate the effects of limited flexibility on the
      transport properties of semiflexible, monodisperse, double-stranded, blunt-ended
      DNA restriction fragments. We study a homologous series of fragments with 400,
      800, and 1600 base pairs (3 to 11 persistence lengths), which are specifically
      designed and synthesized for this purpose (Part I). The molecular weights
      following from the sedimentation measurements agree well with the values expected
      on the basis of the number of base pairs. The sedimentation coefficients at
      infinite dilution are in good agreement with theoretical predictions for wormlike
      cylinders. The first order in volume fraction (varphi) coefficient K of the
      varphi-dependent sedimentation coefficient s(varphi)=1-Kvarphi decreases from
      1178 for the shortest fragment to 882 for the longest fragment. These values are
      much larger than predicted for uncharged rigid rods, indicating the presence of
      associates with an enhanced aspect ratio and excluded volume. The precise match
      of the molecular weights obtained from exponential sedimentation-diffusion
      equilibrium distributions with weights calculated from the number of base pairs
      shows that any association is reversible and disappears at sufficiently low DNA
      concentration.

PMID- 15993889
TI  - Layered double hydroxide hybrids with dicetylphosphate.
AB  - Dicetyl phosphate (DCP) ions incorporated into layered double hydroxide (LDH)
      clays to form a DCP/LDH hybrid were prepared and structurally characterized by X
      ray diffraction analysis, scanning electron microscopy, thermogravimetry, and
      differential thermal analyses. DCP was concluded not only to form well-aligned
      bilayer structures along the vertical axis of the LDH layers but also to be
      arranged in a distorted hexagonal packing orientation in the lateral planes
      within the DCP/LDH hybrid interlayers.

PMID- 15993890
TI  - A comparability study of the emerging protein array platforms with established
      ELISA procedures.
AB  - Recent developments in microarray technology have made it possible to perform
      immunoassays in a multiplexed format. This ability is highly desirable given the
      potential for greater throughput analysis. In spite of the obvious advantages, a
      number of issues arise as a result of multiplexing the reactions. In this study,
      we have assessed the performance characteristics that are associated with the
      transfer of technology from a uniplexed to a multiplexed format. Two solution
      phase array platforms were chosen for this study: the commercially available
      Luminex(100) xMap system (Austin, Texas, USA) and the UltraPlex technology
      devised by SmartBead Technologies Ltd. (Cambridge, UK). For this comparative
      study, a test for the presence of six autoantibodies in a selection of human
      patient serum samples was chosen as a model system. The multiplexed Luminex xMap
      and SmartBead UltraPlex assays were generally comparable. However, both systems
      generated some results that were at variance with those obtained by ELISA. The
      different methods used for the assignment of the cut-off levels for each of the
      assays within any given platform was identified as the major source of these non
      concordant results. The present study demonstrates that array platforms have the
      potential to be used in immunodiagnostics providing that suitable cut-off levels
      are established.

PMID- 15993891
TI  - Actin redistribution in mosquito malpighian tubules after a blood meal and cyclic
      AMP stimulation.
AB  - Fluid secretion by mosquito Malpighian tubules is critical to maintaining fluid
      and electrolyte balance after a blood meal. Endogenous cAMP levels increase in
      Malpighian tubules after a blood meal. Here, we determined if corresponding
      changes in intracellular actin distribution occur after a blood meal or dibutyryl
      cAMP (db-cAMP) stimulation and whether altering actin turnover inhibits
      secretion. In untreated Malpighian tubules, beta-actin immunostaining was more
      intense in the apical region of adult Malpighian tubules than in the cytoplasm.
      Stimulation by a blood meal or db-cAMP significantly decreased beta-actin
      immunostaining in the non-apical region of the cell. Db-cAMP had similar effects
      in larvae and pupae Malpighian tubules. In contrast, no detectable shift in F
      actin distribution was detected; however, F-actin bundles within the cytoplasm
      increased in size after treatment with db-cAMP. Pretreatment of Malpighian
      tubules with agents perturbing actin fiber assembly and disassembly decreased
      basal secretion rates and inhibited the stimulatory effects of db-cAMP. Our
      results show (1) beta-actin redistributes toward the apical membrane after a
      blood meal and this correlates temporally with increase urine flow rate and
      intracellular cAMP levels, (2) Malpighian tubules from all developmental stages
      exhibit this same response to db-cAMP-stimulation, and (3) dynamic assembly and
      disassembly of beta-actin is required for db-cAMP-stimulated secretion.

PMID- 15993892
TI  - Crystal structures of recombinant human purple Acid phosphatase with and without
      an inhibitory conformation of the repression loop.
AB  - The crystal structure of human purple acid phosphatase recombinantly expressed in
      Escherichia coli (rHPAP(Ec)) and Pichia pastoris (rHPAP(Pp)) has been determined
      in two different crystal forms, both at 2.2A resolution. In both cases, the
      enzyme crystallized in its oxidized (inactive) state, in which both Fe atoms in
      the dinuclear active site are Fe(III). The main difference between the two
      structures is the conformation of the enzyme "repression loop". Proteolytic
      cleavage of this loop in vivo or in vitro results in significant activation of
      the mammalian PAPs. In the crystals obtained from rHPAP(Ec), the carboxylate side
      chain of Asp145 of this loop acts as a bidentate ligand that bridges the two
      metal atoms, in a manner analogous to a possible binding mode for a phosphate
      ester substrate in the enzyme-substrate complex. The carboxylate side-chain of
      Asp145 and the neighboring Phe146 side-chain thus block the active site, thereby
      inactivating the enzyme. In the crystal structure of rHPAP(Pp), the enzyme
      "repression loop" has an open conformation similar to that observed in other
      mammalian PAP structures. The present structures demonstrate that the repression
      loop exhibits significant conformational flexibility, and the observed alternate
      binding mode suggests a possible inhibitory role for this loop.

PMID- 15993893
TI  - DNA-induced conformational changes in type II restriction endonucleases: the
      structure of unliganded HincII.
AB  - The 2.1A crystal structure of the unliganded type II restriction endonuclease,
      HincII, is described. Although the asymmetric unit contains only a single
      monomer, crystal lattice contacts bring two monomers together to form a dimer
      very similar to that found in the DNA bound form. Comparison with the published
      DNA bound structure reveals that the DNA binding pocket is expanded in the
      unliganded structure. Comparison of the unliganded and DNA liganded structures
      reveals a simple rotation of subunits by 11 degrees each, or 22 degrees total, to
      a more closed structure around the bound DNA. Comparison of this conformational
      change to that observed in the other type II restriction endonucleases where DNA
      bound and unliganded forms have both been characterized, shows considerable
      variation in the types of conformational changes that can occur. The
      conformational changes in three can be described by a simple rotation of
      subunits, while in two others both rotation and translation of subunits relative
      to one another occurs. In addition, the endonucleases having subunits that
      undergo the greatest amount of rotation upon DNA binding are found to be those
      that distort the bound DNA the least, suggesting that DNA bending may be less
      facile in dimers possessing greater flexibility.

PMID- 15993894
TI  - Describing RNA structure by libraries of clustered nucleotide doublets.
AB  - The rapidly increasing wealth of structural information on RNA and knowledge of
      its varying roles in biology have facilitated the study of RNA structure using
      computational methods. Here, we present a new method to describe RNA structure
      based on nucleotide doublets, where a doublet is any two nucleotides in a
      structure. We restrict our search to doublets that are close together in space,
      but not necessarily in sequence, and obtain doublet libraries of various sizes by
      clustering a large set of doublets taken from a data set of high-resolution RNA
      structures. We demonstrate that these libraries are able to both capture
      structural features present in RNA and fit local RNA structure with a high level
      of accuracy. Libraries ranging in size from ten to 100 doublets are examined, and
      a detailed analysis shows that a library with as few as 30 doublets is sufficient
      to capture the most common structural features, while larger libraries would be
      more appropriate for accurate modeling. We anticipate many uses for these
      libraries, from annotation to structure refinement and prediction.

PMID- 15993895
TI  - Posterior cingulate gyrus metabolic changes in chronic schizophrenia with
      generalized cognitive deficits.
AB  - N-Methyl-d-aspartate (NMDA) receptor antagonists are known to induce
      schizophrenia-like psychotic symptoms and cognitive deficits in humans, and have
      been shown to cause neuronal damage in the posterior cingulate gyrus (PCG) of
      rodents. Patients with chronic schizophrenia exhibit generalized cognitive
      deficits, but it remains unclear whether or not the PCG is related to their
      cognitive dysfunction. To determine what biochemical changes may occur in the PCG
      of patients with chronic schizophrenia, and to ascertain whether or not such
      abnormalities may be related to the incidence of cognitive deficits, we obtained
      cognitive scores and proton magnetic resonance spectra (MRS) from the PCG and the
      left and right medial temporal lobes (MTL) of 19 patients with schizophrenia and
      18 age- and sex-matched normal healthy controls. Compared to the normal controls,
      the patients with chronic schizophrenia showed significantly worse cognitive
      performance on verbal and visual memory tests, verbal fluency tests, and the
      Trail Making Test. The ratio of N-acetylaspartate to creatine and phosphocreatine
      (NAA/Cr) in the PCG of the patients was significantly lower than that of the
      controls. Moreover, the NAA/Cr in the PCG of the healthy controls exhibited age
      related decline, whereas in the patients with schizophrenia, the corresponding
      values were consistently low, regardless of age. These findings are thus in
      accord with current speculation about neuronal dysfunction in the PCG based on
      the NMDA hypofunction hypothesis regarding the pathophysiology of chronic
      schizophrenia.

PMID- 15993896
TI  - Association of C-reactive protein elevation with trait aggression and hostility
      in personality disordered subjects: a pilot study.
AB  - OBJECTIVE: The presence of personality traits of aggression and hostility, in
      generally healthy human subjects, has been shown to be associated with elevations
      of C-reactive protein (pCRP), which, in turn, has also been shown to be
      associated with an increased risk of cardiac disease. In this pilot study, the
      author tests the hypothesis that pCRP elevations are associated with the traits
      of aggression and hostility in personality disordered subjects, a group at high
      risk for the presence of aggression and hostility. METHOD: Participants were 99
      medically healthy subjects meeting DSM-IV criteria for personality disorder for
      which both pCRP levels and Buss-Durkee Hostility Inventory (BDHI) Aggression and
      Hostility data were available. RESULTS: Subjects with pCRP levels > or = 1.0 mg/L
      or higher were found to have significantly higher BDHI Aggression and BDHI
      Hostility scores than subjects with pCRP levels < 1.0 mg/L. Addition of a number
      of control variables reduced, but did not generally eliminate, differences in the
      BDHI scores. In contrast, measures of general dimensions of personality did not
      differ as a function of pCRP Status. CONCLUSIONS: The association of elevations
      in pCRP level in medically healthy personality disordered subjects with higher
      scores of trait aggression and hostility suggests the presence of chronic
      inflammation in highly aggressive/hostile personality disordered subjects similar
      to that observed in otherwise healthy individuals at risk for coronary artery
      disease. Further studies are warranted to determine the clinical correlates of
      this finding.

PMID- 15993897
TI  - Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation.
AB  - BACKGROUND: Our previous study found that silymarin (SM) and its major pure
      component silibinin (SB) have anti-angiogenic effects via decreased vascular
      endothelium growth factor (VEGF) secretion of LoVo cells (colon cancer). We
      designed this consecutive study to evaluate the anti-angiogenic effects of SM/SB
      in vivo, and on VEGF receptor (VEGFR) gene expression. MATERIALS AND METHODS: We
      used LoVo cells exposed to SM/SB in a modified chicken chorioallantoic membrane
      assay (CAM) to evaluate anti-angiogenic effects. We used EA.hy 926 cells
      (endothelial cells) exposed to SM/SB to evaluate the effect on VEGFR-1 (Flt-1)
      and VEGFR-2 (KDR), with 1-step, real-time quantitative reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: In CAM, SM/SB showed a dose
      dependent decrease on the vascular density index (VDI) induced by LoVo cells, as
      did thalidomide in a concentration of 10 microg/ml. Adding escalating dosages of
      VEGF successfully reversed this inhibitory effect. RT-PCR revealed that SB up
      regulated Flt-1 mRNA expression of EA.hy 926 cells. SM had a similar trend,
      although the effect was not statistically significant (P = 0.19). Neither drug
      effected KDR mRNA expression. CONCLUSION: We conclude that anti-angiogenic
      effects of SM/SB are associated with the up-regulation of VEGFR-1 (Flt-1) gene
      expression and that they are good candidates for combination therapy to treat
      colorectal cancer.

PMID- 15993898
TI  - Neutral endopeptidase determines the severity of pancreatitis-associated lung
      injury.
AB  - BACKGROUND: Neutral endopeptidase (NEP) is a cell-surface metalloprotease that
      degrades proinflammatory peptides such as substance P, neurokinin A, and
      bradykinin. Inhibition of NEP exacerbates both experimental pancreatitis and the
      associated lung injury. It is unclear if worsened lung injury is the indirect
      result of more severe pancreatitis or if it is a direct effect of NEP inhibition
      in the lung. MATERIALS AND METHODS: We used a model of pancreatitis-associated
      lung injury (PALI) to test the hypothesis that antagonism or genetic deletion of
      NEP augments PALI inflammation and pulmonary damage irregardless of the degree of
      pancreatitic inflammation. RESULTS: In NEP(+/+) mice, intraperitoneal injection
      of porcine pancreatic elastase (elastase, 0.085 U/g at t = 0 h and t = 1 h)
      caused a 7-fold increase in lung myeloperoxidase (MPO) activity and marked
      pulmonary edema, neutrophil infiltration, and hemorrhage at 4 h as compared to
      control animals. The pattern of lung injury induced by elastase mimicked that
      observed among a separate group of animals with PALI induced by cerulein but was
      not associated with pancreatitis. Both NEP(-/-) mice and NEP(+/+) mice pretreated
      with the NEP antagonist phosphoramidon (10 mg/kg s.c.) had significant elevations
      of lung MPO and worsened lung histology compared to NEP(+/+) mice given elastase
      alone. Antagonism of either the vanilloid receptor transient receptor vanilloid 1
      or the substance P receptor NK1-R had no effect on elastase-mediated lung injury
      in NEP-deficient mice. CONCLUSIONS: NEP is an inhibitor of pancreatic elastase
      induced lung injury, presumably via degradation of proinflammatory mediators.

PMID- 15993899
TI  - Impact of gene-modified T cells on HIV infection dynamics.
AB  - Previous clinical trials in HIV-infected patients involving infusion of T cells
      protected by an antiviral gene have failed to show any therapeutic benefit. The
      value of such a treatment approach is thus still highly controversial. In this
      study, the anticipated effects of gene-modified cells on virus and T-cell
      kinetics are analysed by mathematical modeling. Because technically only a small
      fraction of all T cells in a patient can be manipulated ex vivo, therapeutic
      success will depend on the accumulation of gene-modified cells after infusion
      into the patient by in vivo selection. Our simulations predict that a significant
      therapeutic benefit is conferred only by antiviral genes that inhibit HIV
      replication before virus integration (class I genes). Genes that inhibit viral
      protein expression (class II, used in previous clinical trials), require a much
      higher inhibitory activity than class I genes to promote the regeneration of T
      cells and reduce the viral load. Inhibition of virus assembly and release alone
      (class III) confers no selective advantage to the T cell and is therefore
      ineffective unless combined with class I (or, possibly, class II) genes. Also
      crucial in determining the clinical outcome are the regenerative capacity of the
      gene-modified cells and the level of HIV replication in the patient. These
      results can be important for guiding future strategies in the field of gene
      therapy for HIV infection.

PMID- 15993900
TI  - A model predictive control based scheduling method for HIV therapy.
AB  - Recently developed models of the interaction of the human immune system and the
      human immunodeficiency virus (HIV) suggest the possibility of using interruptions
      of highly active anti-retroviral therapy (HAART) to simulate a therapeutic
      vaccine and induce cytotoxic lymphocyte (CTL) mediated control of HIV infection.
      We have developed a model predictive control (MPC) based method for determining
      optimal treatment interruption schedules for this purpose. This method provides a
      clinically implementable framework for calculating interruption schedules that
      are robust to errors due to measurement and patient variations. In this paper, we
      discuss the medical motivation for this work, introduce the MPC-based method,
      show simulation results, and discuss future work necessary to implement the
      method.

PMID- 15993901
TI  - Local pharmacological preconditioning increases the survival of experimental skin
      flaps in rats.
AB  - Skin flap survival is dependent on an adequate blood supply and on the resistance
      to ischemia. Experimentally we tested the effect of pharmacological
      preconditioning on the survival of skin flaps. The survival of an ischemic skin
      flap (McFarlane flap) was tested using the local application of cobalt gel in
      three groups of Wistar rats. The mean flap necrosis of the control group was
      59.15%. The rats treated by the cobalt gel once a week showed mean necrosis in
      39.09%; the rats receiving the application of the cobalt gel three times a week
      in 26.33%. The treated groups presented with significantly lower flap necrosis in
      comparison to the untreated controls. There was a significant difference in the
      flap necrosis occurrence according to the application frequency of the cobalt
      gel. The expression of the genes involved in angiogenetic processes encoding
      vascular endothelial growth factor (VEGF) and glycolytic enzymes was influenced
      in a non-mitochondrial way in this study. The results show that non-mitochondrial
      preconditioning could prolong the survival of an ischemic flap.

PMID- 15993902
TI  - Analytical solution of the cable equation with synaptic reversal potentials for
      passive neurons with tip-to-tip dendrodendritic coupling.
AB  - A passive cable model is presented for a pair of electrotonically coupled neurons
      in order to investigate the effects of tip-to-tip dendrodendritic gap junctions
      on the interaction between excitation and either pre or postsynaptic inhibition.
      The model represents each dendritic tree by a tapered equivalent cylinder
      attached to an isopotential soma. Analytical solution of the cable equation with
      synaptic reversal potentials is considered for each neuron to yield a system of
      Volterra integral equations for the voltage. The solution to the system of linear
      integral equations (expressed as a Neumann series) is used to determine the
      current spread within the two coupled neurons, and to re-examine the sensitivity
      of the soma potentials (in particular) to the coupling resistance for various
      loci of synaptic inputs. The model is actually posed generally, so that active as
      well as passive properties could be considered. In the active case, a system of
      non-linear integral equations is derived for the voltage.

PMID- 15993903
TI  - Microvascular flow routes in muscle controlled by vasoconstrictors.
AB  - Vasoconstrictors can either increase or decrease metabolism of the constant flow
      pump-perfused rat hindlimb. In addition, there is indirect evidence from vascular
      casts, surface fluorometry, dye entrapment studies, and fluorescent microsphere
      mapping of flow that this may be due to redistribution of flow between putatively
      nutritive and non-nutritive routes within muscle. In the present study, we used
      two methods in an attempt to identify perfused nutritive and non-nutritive
      vessels in muscle sections: (i) a combination of perfusion fixation with
      glutaraldehyde and post-perfusion Griffonia simplicifolia lectin and (ii)
      perfusion with rhodamine-dextran70 (lysine fixable) and post-fixation with
      formaldehyde. Perfusions involved vehicle only (control, a mix of nutritive and
      non-nutritive flow), 15 nM angiotensin II (AII) to increase, or 1 microM
      serotonin (5-HT) to decrease nutritive flow. Microscopic examination of muscle
      sections following AII showed an increase in perfused capillaries with fewer
      areas of under-perfusion, relative to control. In contrast, 5-HT caused a marked
      decrease in perfused capillaries relative to control and evidence that flow was
      carried by connective tissue vessels that on average were of greater diameter and
      were more sparsely distributed than capillaries. It is concluded that
      vasoconstrictors that alter hindlimb metabolism do so by intra-muscle
      redistribution between capillaries (nutritive) and non-nutritive (connective
      tissue) vessels within each muscle.

PMID- 15993904
TI  - Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure.
AB  - Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer.
      The limited impact of standard therapeutic treatments on survival rates makes the
      identification of factors that increase the individual risk a leading priority.
      The high proportion of cases explained by exposure to asbestos has guided
      intervention policies to an effective ban of this compound from our environment.
      However, MM cannot be solely attributed to this agent, and the role of
      predisposing factors and their interaction with asbestos exposure is increasingly
      studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating
      susceptibility to MM was examined in a case-control study of 80 subjects with a
      confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed
      a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The
      association was stronger in the group with low asbestos exposure (OR, 7.83; 95%
      CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast
      acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between
      genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT
      p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction
      observed with exposure to asbestos, suggests the presence of gene-environment and
      gene-gene interactions in the development of MM, although the size of the study
      group does not allow to draw clearcut conclusions. Since genetic polymorphisms
      can also modify the extent of genetic damage occurring in subjects exposed to
      carcinogens, we measured the frequency of micronuclei in peripheral blood
      lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not
      allow to observe significant effects. In conclusion, these results strengthen the
      hypothesis that individual susceptibility to MM can be modulated by the
      interaction between polymorphic genes involved in the metabolism and the
      intensity of asbestos exposure.

PMID- 15993905
TI  - Muscarinic receptor stimulation reduces NMDA responses in CA3 hippocampal
      pyramidal cells via Ca2+-dependent activation of tyrosine phosphatase.
AB  - N-methyl-D-aspartate (NMDA)-type glutamate receptors perform critical functions
      during the development of the nervous system and in the initiation of synaptic
      plasticity. An important mechanism in setting the gain of NMDA receptors involves
      the stimulation of G-protein-coupled receptors (GPCRs), which through activation
      of protein tyrosine kinases leads to an upregulation of NMDA receptors. In
      contrast, little is known about how NMDA receptors are downregulated. In the
      present study, we characterized a signaling pathway that mediates the depression
      of NMDA receptor function in response to stimulation of muscarinic acetylcholine
      receptors. Whole-cell patch-clamp recordings obtained from CA3 pyramidal cells in
      organotypic slice cultures revealed that under conditions of low intracellular
      calcium buffering application of muscarine-depressed NMDA receptor current. The
      sensitivity of this response to pirenzipine indicated that the M1 acetylcholine
      receptor is mediating this depression. The muscarine-induced depression of NMDA
      current was prevented by blocking G-protein function or after depleting
      intracellular Ca2+ stores with cyclopiazonic acid. Inhibitors of calmodulin
      prevented the depression whereas blocking calcineurin enhanced the depression of
      NMDA currents. Blocking tyrosine phosphatase activity with pervanandate converted
      the muscarine-induced depression into a potentiation of NMDA currents, whereas
      blocking protein kinase A (H-89), Src kinase (PP2, SU6656), or PKC (GF 109203X)
      failed to prevent the depression of NMDA currents. As Src tyrosine kinase is
      known to phosphorylate and upregulate NMDA receptors, we propose that a protein
      tyrosine phosphatase(s) counteracting the action of Src is the final target in
      the mAChR-dependent inhibitory signaling cascade. Our data are consistent with a
      transduction cascade comprising an M1 acetylcholine receptor-->G-protein-->Ca2+
      release-->calmodulin-->tyrosine phosphatase.

PMID- 15993906
TI  - Why has oral rehydration for calves and children diverged: direct vs. indirect
      criteria of efficacy.
AB  - Oral rehydration therapy (ORT) for acute diarrhoea has advanced in contrary
      directions in humans and animals; the unresolved question is whether this
      reflects species differences or a divergence in scientific outlook. This review
      suggests that the explanation lies in the fact that developments in veterinary
      ORT have the advantage of utilising more reliable criteria than those available
      from human patients. The dilemma for human ORT is that the validity of systematic
      reviews and meta-analyses are undermined when the underlying data only reflect
      crucial variables indirectly and unreliably. It is therefore possible that the
      approaches currently used to treat calves, which are radically different from
      those used by paediatricians, could potentially benefit children and the
      necessary additional research should be initiated. At a time when the value of
      animal models of human disease is frequently questioned, the benefits of being
      able to utilise disease models in the target species for clinical research
      deserve to be emphasised.

PMID- 15993907
TI  - Repellent efficacy of four commercial DEET lotions against Amblyomma hebraeum
      (Acari: Ixodidae), the principal vector of Rickettsia africae in southern Africa.
AB  - African tick bite fever, caused by Rickettsia africae, is an emerging zoonotic
      infection in rural sub-Saharan Africa and the French West Indies. We tested the
      repellent efficacy of four commercial diethyl-3-methylbenzamide (DEET) lotions
      against Amblyomma hebraeum Koch, the principal vector of R. africae in southern
      Africa, by using a human bioassay in which repellent-treated fingers were
      presented to questing tick nymphs hourly for 4h. Three lotions with 19.5, 31.6
      and 80% DEET concentrations, respectively, had a repellent efficacy of > or =90%
      at 1h post-application, of > or =77% at 2h post-application and of <70% during
      the rest of the experiment. By contrast, a lotion with 2% DEET plus 1% citronella
      oil provided only a 59% repellency at 1h post-application, with a drop to <22%
      during the following hours. Hourly negative control trials repelled <5% of tick
      attacks. Our results suggest that commercial repellents containing > or =19.5%
      DEET provide a significant but short-lasting protection against questing A.
      hebraeum ticks.

PMID- 15993908
TI  - The problem with dengue.

PMID- 15993909
TI  - Toxicological implications of polymorphisms in receptors for xenobiotic
      chemicals: the case of the aryl hydrocarbon receptor.
AB  - Mechanistic toxicology has predominantly been focused on adverse effects that are
      caused by reactive metabolites or by reactive oxygen species. However, many
      important xenobiotics exert their toxicity, not by generating reactive products,
      but rather by altering expression of specific genes. In particular, some
      environmental contaminants target nuclear receptors that function as regulators
      of transcription. For example, binding of xenobiotic chemicals to steroid
      receptors is a principle mechanism of endocrine disruption. The aryl hydrocarbon
      receptor (AHR) mediates toxicity of dioxin-like compounds. In mice, a
      polymorphism in the AHR ligand-binding domain reduces binding affinity by about
      10-fold in the DBA/2 strain compared with the C57BL/6 strain; consequently, dose
      response curves for numerous biochemical and toxic effects are shifted about one
      log to the right in DBA/2 mice. In the Han/Wistar (Kuopio) (H/W) rat strain, a
      polymorphism causes a deletion of 38 or 43 amino acids from the AHR
      transactivation domain. This deletion is associated with a greater than 1000-fold
      resistance to lethality from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Genes in
      the conventional AH gene battery (e.g. CYP1A1, CYP1A2, CYP1B1, ALDH3A1, NQO1 and
      UGT1A1) remain responsive to TCDD in H/W rats despite the large deletion.
      However, the deletion may selectively alter the receptor's ability to dysregulate
      specific genes that are key to dioxin toxicity. We are identifying these genes
      using an expression array approach in dioxin-sensitive vs. dioxin-resistant rat
      strains and lines. Polymorphisms exist in the human AH receptor, but thus far
      they have not been shown to have any substantial effect on human responses to AHR
      ligands.

PMID- 15993910
TI  - Gene expression influences on metal immunomodulation.
AB  - Heavy metals in the environment originate from both human activities and natural
      processes. Exposure to these metals can result in important changes to immune
      activity. Depending on the metal and dose, these changes can result in enhanced
      immune function, diminished immune responses, or altered responses that produce
      autoimmune disease. One of the intriguing aspects of these various phenomena are
      the multiple points of interaction with cellular machinery at which metals elicit
      these changes. The individual sections of this review serve to underscore the
      variety of targets that can be altered by exposure to heavy metals, and provide
      some comparisons between the effects of specific heavy metals on the immune
      system. These observations may ultimately lead us to a comprehensive
      understanding of the mechanisms by which metals alter the immune system, and may
      enable the development of countermeasures to offset these effects.

PMID- 15993911
TI  - Regulation of cytokine production in human alveolar macrophages and airway
      epithelial cells in response to ambient air pollution particles: further
      mechanistic studies.
AB  - In order to better understand how ambient air particulate matter (PM) affect lung
      health, the two main airway cell types likely to interact with inhaled particles,
      alveolar macrophages (AM) and airway epithelial cells have been exposed to
      particles in vitro and followed for endpoints of inflammation, and oxidant
      stress. Separation of Chapel Hill PM 10 into fine and coarse size particles
      revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was
      driven by material present in the coarse PM, containing 90-95% of the stimulatory
      material in PM10. The particles did not affect expression of hemoxygenase-1 (HO
      1), a sensitive marker of oxidant stress. Primary cultures of normal human
      bronchial epithelial cells (NHBE) also responded to the coarse fraction with
      higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size
      PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO
      1 expression. The production of cytokines in AM by both coarse and fine particles
      was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the
      recognition of LPS and Gram negative bacteria. The NHBE were found to recognize
      coarse and fine PM through TLR2, a receptor with preference for recognition of
      Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal
      cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF
      and IL-8 release in AM. Both coarse and fine ambient air PM were also found to
      inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no
      inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor
      protein accumulation but interfered with the release of cytokine from the cells.
      Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and
      protein production. Exposure to coarse and fine PM decreased the expression of
      TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness
      to LPS may be related to LPS tolerance induced by low levels of LPS.

PMID- 15993912
TI  - The ethical basis of the precautionary principle in health care decision making.
AB  - This article explores the relation between the precautionary and health care
      decision making. Decision making in medical practice as well as health policy is
      characterized by uncertainty. On the level of clinical practice for example, one
      never knows in advance whether one has made the right diagnosis or has opted for
      the right treatment. Though medical decisions have a risk on serious harms and
      burdens, the precautionary principle is not applicable to health care. This
      principle holds that one should not act when there is no scientific proof that no
      harms will result from a medical act or a policy decision. However, in clinical
      practice there is a duty to act. Physicians have an obligation to do good to
      their patients and have to weigh the benefits against possible harms and burdens.
      The basis virtue of medical decision making is not avoidance of risks, as stated
      in the precautionary principle, but the prudent assessment of benefits, burdens,
      and harms, in relation to other ethical principles like respect for autonomy and
      justice. The precautionary principle does play a role in health care, but it
      should never rule medical decision making as an absolute principle. This is not
      only true for clinical decision making, but also for the area of health policy.
      Physicians and other health care decision makers need to have knowledge about the
      possible effects of treatments or the precision of diagnostic procedures in order
      to reduce harm and promote well-being. Evidence-based medicine may contribute to
      the wisdom of health care decision makers, but this evidence-based wisdom should
      always be applied under the guidance of prudence, which is the central virtue of
      health care decision making.

PMID- 15993913
TI  - Toxicological implications of esterases--from molecular structures to functions.
AB  - This article reports on a keynote lecture at the 10th International Congress of
      Toxicology sponsored by the International Union of Toxicology and held on July
      2004. Current developments in molecular-based studies into the structure and
      function of cholinesterases, carboxylesterases, and paraoxonases are described.
      This article covers mechanisms of regulation of gene expression of the various
      esterases by developmental factors and xenobiotics, as well as the interplay
      between physiological and chemical regulation of the enzyme activity.

PMID- 15993914
TI  - Full length nucleotide sequence of a factor V-like subunit of oscutarin from
      Oxyuranus scutellatus scutellatus (coastal Taipan).
AB  - An Oxyuranus scutellatus scutellatus venom gland cDNA expression library was
      screened with antivenom. Positive clones were isolated and their nucleotide
      sequences determined. The complete sequence for a Factor V-like component from
      the Taipan venom prothrombin activator, oscutarin (EC 3.4.21.60) (Walker, F.J.,
      Owen, W.G., Esmon, C.T., 1980. Characterization of the prothrombin activator from
      the venom of Oxyuranus scutellatus scutellatus (Taipan venom). Biochemistry,
      19(5), 1020-1023; Speijer, H.G.R., Zwall, J., Robert, F.A., Rosing, J., 1986.
      Prothrombin acitvation by an activator from the venom of Oxyuranus Scutellatus
      (Taipan Snake). J. Biol. Chem. 261, 13258-13267) was determined from the
      sequencing of antigenic cDNA clones. The cDNA sequence encoded a protein of 1460
      amino acid residues, including a 30-residue signal peptide. This sequence shared
      95% sequence similarity with the non-enzymic subunit of the prothrombin activator
      (pseutarin C) from brown snake (Pseudonaja textilis) venom. This sequence in turn
      has been reported to share high similarity with mammalian Factor V. Sequence
      comparisons indicated the size, charge and cleavage sites were conserved across
      the two species. This is the first nucleotide sequence of a Factor V-like
      component from Oxyuranus venom and the second sequence within Elapidae to be
      reported.

PMID- 15993915
TI  - Mutational analysis of the direct tandem repeat sequences at the origin of DNA
      replication of porcine circovirus type 1.
AB  - Mutational analysis was conducted to investigate the role of the nucleotide
      sequences flanking the stem-loop palindromic structure at the origin of DNA
      replication of porcine circovirus type 1 (PCV1) with respect to self-DNA
      replication and progeny virus generation. The results demonstrated that the A
      rich sequence to the left of the palindrome is non-essential for virus
      replication. Although a set of four hexanucleotide (H) sequences to the right of
      the palindrome (organized in two tandem repeats: the proximal H1/H2 and the
      distal H3/H4) are binding sites for the viral Rep-associated proteins in vitro,
      only a proximal tandem (H/H or h-like/H) is essential for PCV1 DNA replication.
      In the presence of H1/H2, mutations engineered into H3/H4 were preserved in the
      progeny viruses. Mutations engineered into H1/H2 were invariably deleted so that
      the downstream H3/H4 was placed next to the palindrome. Viral genome with
      mutations engineered into both H1/H2 and H3/H4 underwent extensive nucleotide
      reorganization to yield progeny viruses containing either H3/H4, h-like/H4, or h
      like/H3/H4 sequences.

PMID- 15993916
TI  - Imbalance of tumor necrosis factor receptors during progression in bovine
      leukemia virus infection.
AB  - Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-alpha
      and an imbalance of TNF receptors in sheep experimentally infected with bovine
      leukemia virus (BLV). In order to investigate the different TNF-alpha-induced
      responses, in this study we examined the TNF-alpha-induced proliferative response
      and the expression levels of two distinct TNF receptors on peripheral blood
      mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected
      cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The
      proliferative response of PBMC isolated from those cattle with PL in the presence
      of recombinant bovine TNF-alpha (rTNF-alpha) was significantly higher than those
      from AL cattle and uninfected cattle and the cells from PL cattle expressed
      significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those
      from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels.
      Most cells expressing TNF-RII in PL cattle were CD5+ or sIgM+ cells and these
      cells showed resistance to TNF-alpha-induced apoptosis. Additionally, there were
      significant positive correlations between the changes in provirus load and TNF
      RII mRNA levels, and TNF-alpha-induced proliferation and TNF-RII mRNA levels.
      These data suggest that imbalance in the expression of TNF receptors could at
      least in part contribute to the progression of lymphocytosis in BLV infection.

PMID- 15993917
TI  - Enhanced immunogenicity and protective effect conferred by vaccination with
      combinations of modified vaccinia virus Ankara and licensed smallpox vaccine
      Dryvax in a mouse model.
AB  - Significant adverse events are associated with vaccination with the currently
      licensed smallpox vaccine. Candidate new-generation smallpox vaccines such as the
      replication-defective modified vaccinia virus Ankara (MVA) produce very few
      adverse events in experimental animals and in limited human clinical trials
      conducted near the end of the smallpox eradication campaign. Efficacy evaluation
      of such new-generation vaccines will be extraordinarily complex, however, since
      the eradication of smallpox precludes a clinical efficacy trial and the
      correlates of protection against smallpox are unknown. A combination of relevant
      animal efficacy studies along with thorough comparative immunogenicity studies
      between traditional and new-generation smallpox vaccines will be necessary for
      vaccine licensure. In the present study, a variety of immune responses elicited
      by MVA and the licensed smallpox vaccine Dryvax in a murine model were compared,
      with a focus on mimicking conditions and strategies likely to be employed in
      human vaccine trials. Immunization of mice with MVA, using several relevant
      vaccination routes including needle-free delivery, elicited humoral and cellular
      immune responses qualitatively similar to those elicited by vaccination with
      Dryvax. Similar levels of vaccinia-specific IgG and neutralizing antibody were
      elicited by Dryvax and MVA when higher doses (approximately 1 log) of MVA were
      used for immunization. Antibody levels peaked at about 6 weeks post-immunization
      and remained stable for at least 15 weeks. A booster immunization of either MVA
      or Dryvax following an initial priming immunization with MVA resulted in an
      enhanced IgG titer and neutralizing antibody response. In addition, both Dryvax
      and various MVA vaccination protocols elicited antibody responses to the
      extracellular enveloped form of the virus and afforded protection against a
      lethal intranasal challenge with vaccinia virus WR.

PMID- 15993918
TI  - Global speed averaging is tuned for binocular disparity.
AB  - The extent to which local speeds at different depths are averaged to determine
      global speed was determined using a version of the Global Dot Motion (GDM)
      stimulus. Judgments of the apparent speed of fast moving dots (4.05-10.53 deg/s)
      in the presence of slow moving dots (4.05 deg/s) were measured using GDM stimuli
      which simulated radially expanding motion, and which confined slow and fast speed
      dots exclusively to alternating wedge shaped sectors. The presence of slow moving
      dots in the stimulus reduced the apparent speed of high-speed dots in a manner
      consistent with speed averaging. However with increases in depth, produced by a
      difference in binocular disparity between dots in alternating sectors, speed
      averaging became less effective, and the relationship between speed and disparity
      resembled a tuning function. We discuss our results in light of research that
      clarifies the functional properties of global motion mechanisms in the primate
      cortex.

PMID- 15993919
TI  - Contrast sensitivity of wildtype mice wearing diffusers or spectacle lenses, and
      the effect of atropine.
AB  - PURPOSE: To find out how spatial vision in mice is affected by wearing of
      spectacle lenses or diffusers, and by atropine eye drops. This information is
      necessary to determine which treatments could effectively induce refractive
      errors in young mice. METHODS: Whole-body optomotor responses were recorded by
      automated video analysis in freely ranging mice in a large rotating drum that was
      covered inside with vertical square-wave gratings with spatial frequencies of
      0.03, 0.10 and 0.30 cyc/deg, both at "dim light" (0.10 cd/m(2)), and under
      photopic conditions (30 cd/m(2)). Contrast thresholds were determined by varying
      the contrasts of the gratings. Mice wore either no lenses, or binocular plano
      lenses, or lenses with powers ranging from +25 D to -25 D, or diffusers. In
      another experiment, contrast thresholds were determined 30 min after binocular
      installation of one drop of 1% atropine solution which is known to suppress
      myopia development in other animal models. RESULTS: The range of spatial
      frequencies, at which the mice still responded to stripes with less than the
      maximal grating contrast, was rather small. At 0.03 cyc/deg, the mice responded
      to stripes with low contrast down to 24%. At 0.10 cyc/deg, the minimal contrast
      was 45%, but at 0.30 cyc/deg, only the maximum contrast elicited a significant
      response. In dim light, spatial vision was severely impaired and only the lowest
      spatial frequencies, presented at the highest contrast (91%), were detected. The
      whole-body optomotor response was largest with spectacle lens powers of plano
      diopters and +7D lenses. The magnitude of the response decreased symmetrically
      with increasing lens powers for both signs, providing information on the
      behavioral depth of field (a second-order fit through the data placed the extreme
      limits of a response at around +25 D and -25 D lens powers). Finally, atropine
      improved contrast sensitivity, at least at the lowest spatial frequency tested, a
      result that was previously obtained also in the chicken and could help to explain
      the inhibitory effect of atropine on myopia. CONCLUSIONS: The study shows that
      mice have sufficient spatial vision to respond to treatment with powerful
      spectacle lenses or diffusers. Accordingly, these devices should be effective in
      inducing refractive errors in this animal model, although primarily under
      photopic conditions.

PMID- 15993920
TI  - Removal of arsenic(III) from aqueous solutions using fresh and immobilized plant
      biomass.
AB  - The ability of Garcinia cambogia, an indigenous plant found in many parts of
      India, to remove trivalent arsenic from solution was assessed. Batch experiments
      were carried out to characterize the As(III) removal capability of fresh and
      immobilized biomass of G. cambogia. It was found that the kinetic property and
      uptake capacity of fresh biomass were significantly enhanced by the
      immobilization procedure. The uptake of As(III) by fresh and immobilized biomass
      was not greatly affected by solution pH with optimal biosorption occurring at
      around pH 6--8. The presence of common ions such as Ca and Mg at concentrations
      up to 100mg/l had no effect on As(III) removal. However, the presence of Fe(III)
      at 100mg/l caused a noticeable drop in the extent of As(III) removal but the
      effect was minimal when Fe(III) was present at 10mg/l. The adsorption isotherms
      quantitatively predicted the extent of As(III) removal in groundwater samples
      collected from an arsenic-contaminated site in India. Immobilized biomass loaded
      with As(III) was amenable to efficient regeneration with NaOH solution. Column
      studies showed that immobilized biomass could be reused over five cycles of
      loading and elution. The excellent As(III) sequestering capability of fresh and
      immobilized G. cambogia biomass could lead to the development of a viable and
      cost-effective technology for arsenic removal in groundwater.

PMID- 15993921
TI  - Enhanced adsorption of Cd (II) on a hydrous Al (III) floc in the presence of a
      modified form of polyethylenimine.
AB  - A polymer modified with succinic anhydride has been investigated for the
      adsorption of cadmium (II) on a freshly precipitated aluminium (III) hydroxide
      floc. The proportion of chelate attached to the polymer is varied to determine
      the relationship between carboxyl and amino groups on the polyelectrolyte, in
      terms of enhanced adsorption of cadmium (II) on a hydrous aluminium floc. The
      presence of polyelectrolyte enhanced the adsorption of 3.3 ppm Cd (II) on a 333
      ppm Al (III) floc at every concentration of polyelectrolyte investigated. The
      proportion of succinic anhydride attached to the polymer had an impact on the
      increased adsorption of Cd (II) on an Al (III) floc observed. A decreasing
      proportion of succinic anhydride to polymer resulted in a decrease in the amount
      of cadmium adsorbed on the floc. Above pH 8, a decrease in the % Cd (II) adsorbed
      on the floc and % Al (III) retained within the floc decreases with the presence
      of polyelectrolyte as a result of the formation of soluble Cd-Polyethylenimine
      succinic acid (PEISA) complexes. When the Al-PEISA combination was applied to a
      complex matrix where Cd (II), Cu (II) and Ni (II) ions competed for adsorption,
      enhanced adsorption was observed for Cd (II) and Ni (II). At pH 7, dissolution of
      the floc observed with the addition of discrete chelates was not observed with
      the addition of polyelectrolytes.

PMID- 15993922
TI  - Pulsed ultra-violet inactivation spectrum of Escherichia coli.
AB  - Inactivation of Escherichia coli is examined using ultra-violet (UV) radiation
      from a pulsed xenon flashlamp. The light from the discharge has a broadband
      emission spectrum extending from the UV to the infrared region with a rich UV
      content. The flashlamp provides high-energy UV output using a small number of
      short-duration pulses (30 micros). The flashlamp is used with a monochromator to
      investigate the wavelength sensitivity of E. coli to inactivation by the pulsed
      UV light. Using 8 nm wide pulses of UV radiation, the most efficient inactivation
      is found to occur at around 270 nm and no inactivation is observed above 300 nm.
      A pyroelectric detector allows the energy dose to be determined at each
      wavelength, and a peak value for E. coli population reduction of 0.43 log per
      mJ/cm(2) is measured at 270 nm. The results are compared with the published data
      available for continuous UV light sources.

PMID- 15993923
TI  - Chromate ion adsorption by agricultural by-products modified with
      dimethyloldihydroxyethylene urea and choline chloride.
AB  - The use of cellulose-containing agricultural by-products modified with the cross
      linking reagent dimethyloldihydroxyethylene urea (DMDHEU) and the quaternary
      amine, choline chloride, as anion exchange resins, has not been reported. The
      objective of the present study was to convert the readily available by-products,
      soybean hulls, sugarcane bagasse and corn stover to functional anion exchange
      resins using DMDHEU and choline chloride. Optimization of the modification method
      was achieved using soybean hulls as a substrate. The optimized method was
      additionally used to modify sugarcane bagasse and corn stover. Adsorption
      efficiency results with chromate ion showed that modification with both DMDHEU
      and choline chloride was required for the highest efficiencies. Adsorption
      capacities of the modified by-products were determined using chromate ion and
      found to be 1.97, 1.61 and 1.12 mmol/g for sugarcane bagasse, corn stover and
      soybean hulls, respectively. Competitive adsorption studies were conducted at 10
      and 50 times US Environmental Protection Agency (US EPA) limits for arsenic,
      chromium and selenium in a simulated wastewater at pH 7. The results showed
      preferential adsorption of chromate ion over arsenate or selenate ion. Estimated
      product costs for the three resins ranged from $0.88/kg to $0.99/kg, which was
      considerably lower than the market costs for the two commercial anion exchange
      resins QA-52 and IRA-400 also used in this study. DMDHEU/choline chloride
      modification of the three by-products produced an anion exchange resin with a
      high capacity to adsorb chromate ion singly or competitively in the presence of
      other anions from aqueous solutions.

PMID- 15993924
TI  - Cyanobacteria and earthy/musty compounds found in commercial catfish (Ictalurus
      punctatus) ponds in the Mississippi Delta and Mississippi--Alabama Blackland
      Prairie.
AB  - The compounds responsible for earthy and musty "off-flavors" in farm-raised
      channel catfish (Ictalurus punctatus) in the southeastern United States of
      America are geosmin and 2-methylisoborneol (MIB), respectively. These compounds
      are produced by certain species of cyanobacteria (blue-green algae) that grow in
      the aquaculture ponds. Previous research has focused on the species of
      cyanobacteria found in catfish ponds in west Mississippi (the leading region of
      catfish production in the USA), while the species responsible for earthy/musty
      off-flavors in catfish produced in the Mississippi-Alabama Blackland Prairie
      (MABP) region (second greatest region of catfish production) have not been
      described. We examined water samples from commercial catfish ponds in both
      regions to contrast the different types of cyanobacteria and assess the
      prevalence of geosmin and MIB. Results established that filamentous cyanobacteria
      are more common in west Mississippi compared to the MABP region. Also, the MIB
      producing cyanobacterium Oscillatoria perornata is present in catfish ponds in
      both geographic locations, and geosmin is more prevalent in catfish ponds in the
      MABP region than in west Mississippi.

PMID- 15993925
TI  - Impact of lamp shadowing and reflection on the fluence rate distribution in a
      multiple low-pressure UV lamp array.
AB  - Use of mathematical modeling for determination of ultraviolet (UV) fluence in
      disinfection reactors requires accurate knowledge of the fluence rate
      distribution in a multiple lamp array. A method for measuring the fluence rate
      among a multiple lamp array was demonstrated using spherical actinometry. A
      matrix of four low-pressure UV lamps in air were investigated to evaluate the
      potential for shadowing and reflection to impact the fluence rate within and
      surrounding the lamp array. Two fluence rate distribution models were tested to
      determine the ability to predict the fluence rate distribution measured by the
      actinometers. Shadowing proved to attenuate UV light. Reflection from the lamp
      surface added 3-9% to the fluence rate, depending upon position in the reactor.
      These effects, as well as the fluence rate at various points in the lamp matrix
      were effectively modeled using RAD-LSI and UVCalc3D fluence rate distribution
      models. At fluence rates above 8mWcm(-2), the actinometry measured fluence rate
      was lower than the modeled rate, presumably from saturation of the actinometer
      solution at high fluence rates (close to the lamp). With multiple lamp reactors,
      the impact of shadowing can significantly affect fluence rate distribution and
      thus the level of microbial inactivation. If shadowing is not included in fluence
      rate distribution models, the fluence rate will be over predicted in the shadow
      zone of a neighboring lamp, falsely skewing model inactivation predictions.

PMID- 15993926
TI  - Evaluation of river water quality monitoring stations by principal component
      analysis.
AB  - The development of a surface water monitoring network is a critical element in
      the assessment, restoration, and protection of stream water quality. This study
      applied principal component analysis (PCA) and principal factor analysis (PFA)
      techniques to evaluate the effectiveness of the surface water quality-monitoring
      network in a river where the evaluated variables are monitoring stations. The
      objective was to identify monitoring stations that are important in assessing
      annual variations of river water quality. Twenty-two stations used for monitoring
      physical, chemical, and biological parameters, located at the main stem of the
      lower St. Johns River in Florida, USA, were selected for the purpose of this
      study. Results show that 3 monitoring stations were identified as less important
      in explaining the annual variance of the data set, and therefore could be the non
      principal stations. In addition, the PFA technique was also employed to identify
      important water quality parameters. Results reveal that total organic carbon,
      dissolved organic carbon, total nitrogen, dissolved nitrate and nitrite,
      orthophosphate, alkalinity, salinity, Mg, and Ca were the parameters that are
      most important in assessing variations of water quality in the river. This study
      suggests that PCA and PFA techniques are useful tools for identification of
      important surface water quality monitoring stations and parameters.

PMID- 15993927
TI  - Cellular replicative capacity correlates primarily with species body mass not
      longevity.
AB  - Although the limited replicative capacity of human fibroblasts in culture is
      frequently used as a model for aging, a question of major interest is whether the
      relationship between in vitro fibroblast proliferative capacity and species
      longevity is primary or secondary to a relationship with species body size. In
      this report we establish that body mass is the primary correlative of
      proliferative potential rather than species life-span.

PMID- 15993928
TI  - Determination of organoarsenic warfare agents in sediment samples from Skagerrak
      by gas chromatography-mass spectrometry.
AB  - In 1945 the Norwegian authorities gave permission to scuttle ships loaded with
      captured chemical ammunition on board in an area approximately 14x4 km in size,
      25 nautical miles south-east of Arendal. An investigation was carried out in 2002
      to inspect four wrecks by using a remote-operated vehicle with video cameras. The
      Norwegian Defence Research Establishment (Forsvarets forskningsinstitutt, FFI)
      carried out the project on behalf of the Norwegian Pollution Control Authority
      (SFT). Sediment samples were collected at eight positions around each wreck. One
      of the wrecks was broken up into several smaller parts. Here sediments were
      collected at one additional position close to one of the parts. From each
      position, at least two sediment cores were taken up to the surface. One of the
      cores from each position was sliced into three parts that were immediately
      frozen. The other whole cores were frozen on board the ship and transported back
      to the laboratory in a freezer. In total, sediment samples from 33 different
      locations were collected and analysed for organoarsenic warfare agents and some
      of their decomposition products by gas chromatography-mass spectrometry (GC-MS)
      after derivatisation with 1-propanethiol. Most of the identified organoarsenic
      compounds found in the sediment samples are parts of the arsine oil mixture
      produced by Germany during World War II. The compounds were found both close to
      the wreck and at a somewhat longer distance from the wrecks. The highest
      concentrations were found in a sediment sample collected close to a bomb seen on
      the seabed. The organoarsenic warfare agents adamsite or lewisite were not found
      in any of the samples. Lewisite is not reported to have been produced during
      World War II, but was nevertheless looked for in the samples.

PMID- 15993929
TI  - Uremic bleeding: pathophysiology and clinical risk factors.
AB  - Renal insufficiency appears clinically to be associated with a bleeding tendency.
      This has been documented in clinical settings including as a complication of
      medical interventions such as surgery and also in spontaneous bleeding events at
      gastrointestinal and intracranial sites. The pathophysiology that underlies this
      tendency appears to involve platelet dysfunction and an imbalance of mediators of
      normal endothelial function. It is also may be complicated by the co-morbidities
      in this population, such as vascular disease, hypertension and anemia, and the
      medical interventions required to treat such co-morbidities. This article reviews
      the evidence, the pathophysiology and the risk factors for increased bleeding in
      patients with chronic renal insufficiency.

PMID- 15993930
TI  - Thromboembolism and anticoagulant management in hemodialysis patients: a
      practical guide to clinical management.
AB  - The need for anticoagulation in dialysis patients is common and the incidence of
      venous thromboembolism (VTE) and atrial fibrillation in this population is high.
      While direct data are lacking on the management of anticoagulation in dialysis
      patients, careful weighing of risks and benefits on the basis of evidence from
      other populations is crucial. VTE should be managed with adjusted dose warfarin
      for most patients. Placement of an inferior vena cava filter is a reasonable
      option for those patients with unacceptable bleeding risks. Studies are ongoing
      to assess the safety of some low-molecular-weight heparins (LMWH), which may
      potentially be useful for long-term anticoagulation in hemodialysis patients. In
      atrial fibrillation the available data on risk of bleeding, risk of stroke, and
      patient preferences should all be taken into account when considering long-term
      anticoagulation. We have constructed an evidence model to help quantitate the
      risks and benefits for an individual patient. The impact of dialysis on risk of
      bleeding is such that the risk of bleeding will outweigh the benefit in many
      patients, and anticoagulation will not be used: in some of these patients aspirin
      therapy may be an alternative. Finally, in the area of prevention of graft and
      access thrombosis, some randomized controlled trials are available, but none have
      to date shown benefit from anticoagulation for primary or secondary prevention of
      thrombosis, and the risk of bleeding in these studies was high.

PMID- 15993931
TI  - ADAMTS-13 activity in von Willebrand disease.

PMID- 15993933
TI  - Feasibility of performing chemoprevention trials in women at elevated risk of
      ovarian carcinoma: initial examination of celecoxib as a chemopreventive agent.
AB  - BACKGROUND: A pilot study was undertaken to determine the feasibility of
      examining a COX-2 inhibitor (Celecoxib) as a chemopreventive agent in women at
      increased risk of ovarian cancer undergoing risk reducing salpingoophorectomy.
      METHODS: Women at elevated inherited risk of ovarian carcinoma pursuing risk
      reducing salpingoophorectomy were eligible for this trial. Ten patients were
      assigned to a control group while 10 patients were administered Celecoxib (400
      mg/day) for 3 months prior to surgery. Demographic data at enrollment was
      collected. Serum, urine, peritoneal fluid, and resected tissues were obtained for
      correlative laboratory study. Evaluation of serum VEGF alterations was examined
      using an ELISA-based assay. RESULTS: Enrollment of patients was completed in 16
      months. Of 29 eligible patients, 20 enrolled onto the study. One patient from
      each group did not complete surgical intervention. No significant differences
      were observed in the enrollment characteristics between the groups. No occult
      cases of ovarian cancer were identified and no differences in the presence of
      follicular cyst, hemorrhagic cysts, or inclusion cysts were noted on initial
      pathologic review. While the mean serum VEGF levels obtained following the
      administration of a COX-2 inhibitor were lower than the pre-administration in 5
      of 6 patients, statistical significance in this difference was not observed (P =
      0.359). However, this is most likely due to the small number of serum samples
      available. CONCLUSION: These results would suggest that chemoprevention trials in
      ovarian cancer will be eagerly embraced by this patient population.

PMID- 15993934
TI  - Two cases of non-Hodgkin's lymphoma presenting as primary gynecologic
      malignancies.
AB  - BACKGROUND: Non-Hodgkin's lymphoma (NHL) presenting as a gynecologic malignancy
      is exceedingly rare. We present two cases of NHL presenting as primary ovarian
      and cervical cancer, respectively. CASE: A 66-year-old female presented with
      abdominal bloating and increased abdominal girth. She underwent a supracervical
      hysterectomy, bilateral salpingo-oophorectomy, and omentectomy for a large pelvic
      mass. Immunophenotyping/flow cytometry revealed monoclonal B-cells positive for
      the CD 20 marker, consistent with NHL. A 47-year-old female presented with
      persistent vaginal discharge and an ulcerative lesion of the cervix. Cervical
      biopsies were non-diagnostic for carcinoma but immunophenotyping demonstrated CD
      20 positive B-cells, consistent with NHL. CONCLUSION: Although uncommon, lymphoma
      should be included in the differential diagnosis of gynecologic malignancies
      because of a favorable outcome when properly diagnosed and treated.

PMID- 15993935
TI  - Correlation of inbred mouse sensitivity to nitrous oxide antinociception with
      brain nitric oxide synthase activity following exposure to nitrous oxide.
AB  - Inhibition of nitric oxide synthase (NOS) antagonizes nitrous oxide (N2O)-induced
      antinociception in mice. This study was conducted to compare brain NOS activity
      in high responding C57BL/6 mice, low responding DBA/2 mice and S5 mice
      selectively bred for low responsiveness to N2O. Exposure to 70% N2O suppressed
      acetic acid-induced abdominal constrictions in C57BL/6 mice but not DBA/2 or S5
      mice. N2O exposure also elevated NOS activity in brains of C57BL/6 mice but not
      DBA/2 or S5 mice. The absence of these effects in DBA/2 or S5 mice is further
      support for the hypothesis that nitric oxide (NO) may play a critical role in N2O
      induced antinociception in mice.

PMID- 15993936
TI  - Assessment of feto-placental well-being in the mare from mid-gestation to term:
      transrectal and transabdominal ultrasonographic features.
AB  - Ultrasound assessment of feto-placental well-being has found its application in
      the equine field, as a valid diagnostic tool. Most reports on equine fetal
      parameters focus on advanced to late gestation. The aim of the present study was
      to further validate the technique of ultrasound evaluation of the equine fetal
      environment, by extending its application to earlier stages of pregnancy. Fetal
      parameters were collected (on 150 pregnancies) over a 3-year period. Data
      included in the study were selected according to the clinical behaviour of the
      mare, the neonate/fetus and fetal membranes at the termination of gestation.
      Validation of the ultrasound technique was also undertaken on a number of
      specimens collected at an abbatoir. At the completion of the study, a substantial
      number of measurements and observations were collected. No fetal parameters
      associated in previous reports with a negative outcome were observed at any of
      the examinations during this study. Therefore, data collected during the present
      study should be of value in feto-placental assessment of well-being, in mid- to
      late-gestation.

PMID- 15993937
TI  - Induction and synchronization of estrus in dogs.
AB  - Indications for estrus induction in the bitch include missed breeding
      opportunities or conception failure, the treatment of primary or secondary
      anestrus and synchronization of ovulation for embryo transfer programs. Reported
      methods for canine estrus induction include the use of synthetic estrogens
      (diethylstilbesterol), dopamine agonists (bromocryptine and cabergoline), GnRH
      agonists (lutrelin, buserelin, fertirelin, deslorelin, and leuprolide) and
      exogenous gonadotropins (luteinizing hormone, follicle stimulating hormone, human
      chorionic gonadotropin, pregnant mare serum gonadotropin, and human menopausal
      gonadotropin). These methods vary widely in efficacy of inducing estrus, as well
      as in the fertility of the induced estrus. The applicability of some of these
      methods for clinical practice is questionable. This review will summarize
      published reports on estrus induction and synchronization in bitches and
      summarize preliminary results using a long-acting injectable preparation of
      deslorelin.

PMID- 15993939
TI  - Genetic sperm defects.
AB  - Genetic sperm defects are specific sperm defects, which have been shown to have a
      genetic mode of transmission. Such genetic linkage, either direct or indirect,
      has been associated with a number of sperm defects in different species, with
      this number increasing with improved diagnostic capabilities. A number of sperm
      defects, which have proven or suspected genetic modes of transmission are
      discussed herein, with particular emphasis on cattle. These include: 1. Acrosome
      defects (knobbed, ruffled and incomplete); 2. Head defects (abnormal
      condensation, decapitated, round head, rolled head, nuclear crest); 3. Midpiece
      abnormalities ("Dag" defect, "corkscrew" defect, "pseudo-droplet" defect); 4.
      Tail defects ("tail stump" defect, primary ciliary dyskinesia).

PMID- 15993938
TI  - The effect of a single oxytocin or carbetocin treatment on uterine contractility
      in early postpartum dairy cows.
AB  - The uterotonic characteristics and effectiveness of a single treatment with
      either oxytocin or carbetocin were quantified in early postpartum dairy cows
      after normal, uncomplicated calvings. Both the short-term (within 4 h), and the
      long-term effects (between 12 and 36 h) of the two treatments were compared.
      Between 14 and 16 h after parturition, 27 multiparous Holstein-Friesian dairy
      cows, without fetal membrane retention, were selected and divided into three
      groups. The first group (n = 9) was administered 50 IU oxytocin intramuscularly,
      the second group (n = 10) received 0.35 mg carbetocin, while animals of the third
      group (n = 8), serving as a control, were administered 5 mL saline solution. A
      transcervically introduced open tip catheter system was used for the non-invasive
      acquisition of the intrauterine pressure (IUP) recording. After digitalization,
      the signals were analyzed, using a specially adapted graphical software program.
      A significant short-term effect was found both in the oxytocin and carbetocin
      treated groups from the analysis of the contraction frequencies (FREQ) and of the
      total area under the curve (TAUC). After significant peaking during the first
      post-treatment hour, the values of the parameters for these two groups remained
      higher during the second hour, returning to the initial levels again during the
      third hour and reaching the level of the control group by the 12th hour. Mean
      amplitude (AMP), duration (DUR) and area under the curve (AUC) of pressure cycles
      were not significantly affected by any of the treatments. Although mean FREQ and
      TAUC significantly declined from the initial values to 12, 24 and 36 h in all
      groups, mean AMP and AUC in the oxytocin and carbetocin treated groups, and mean
      DUR only in the carbetocin treated group to 12 and 36 h, the long-term analysis
      revealed no significant treatment differences for any IUP parameters. Because
      treatment with either oxytocin, or carbetocin elicited similar uterotonic effects
      in healthy, early postpartum cows, it cannot be expected, that using carbetocin
      in preference to oxytocin, will result in a more beneficial clinical effect on
      uterine involution during this period.

PMID- 15993940
TI  - Discoloration of facing and restorative composites by UV-irradiation and staining
      food.
AB  - OBJECTIVES: The purpose of this study was to investigate the color stability of
      five facing (ConquestSculpture: JenericPentron, USA; ThermoresinLC:
      GCCorporation, J; VitaZetaLC: Vita, G; CompoPlus: Degudent, G; belleGlassHP:
      SDSbelle, G) and three restorative (Definite: DeguDent, G; AristonpHc: Ivoclar
      Vivadent, FL; SpectrumTPH: DeTreyDentsply, G) composite materials subject to UV
      irradiation and storage in red wine. METHODS: 16 cylindrical specimen (height 5
      mm, diameter 6 mm) of each material were fabricated. Baseline measurement of the
      CIE-L*a*b* color data was carried out in a reflection spectrophotometer.
      Artificial aging was performed with a filtered xenon lamp (irradiation value: 765
      W/m2). Eight samples of each group were aged and color measured after 24 and 72
      h. Eight specimens were stored in deionized water under light exclusion as a
      control for 10 days. Afterwards all specimen were stored in red wine and color
      measurement took place again after 10 days. Statistical analysis was performed
      using the Mann-Whitney-U-test (p < or = 0.05). RESULTS: The best color stability
      after 72 h of UV-irradiation was shown by ConquestSculpture (DeltaE* = 1.0),
      VitaZeta (DeltaE* = 0.8) and Spectrum (DeltaE* = 0.9). Lowest discoloration for
      the red wine storage was DeltaE* = 1.0 for belleGlass, the highest DeltaE* = 9.8
      for ThermoresinLC. For all materials red wine storage caused more color change in
      the control than in the irradiated group. SIGNIFICANCE: Assuming values of
      DeltaE* < or = 3.3 as clinically acceptable, all tested materials showed
      sufficient color stability during aging. For the facing materials UV-irradiation
      might be recommended to approve resistance to discoloration by staining foods.

PMID- 15993941
TI  - Extracellular matrix-enriched polymeric scaffolds as a substrate for hepatocyte
      cultures: in vitro and in vivo studies.
AB  - Tissue engineering is a promising approach to developing hepatic tissue suitable
      for the functional replacement of a failing liver. The aim of the present study
      was to investigate whether an extracellular cell matrix obtained from fibroblasts
      cultured within scaffolds of hyaluronic acid (HYAFF) could influence the
      proliferation rate and survival of rat hepatocytes both during long-term culture
      and after in vivo transplantation. Cultures were evaluated by histological and
      morphological analysis, a proliferation assay and metabolic activity (albumin
      secretion). Hepatocytes cultured in extracellular matrix-enriched scaffolds
      exhibited a round cellular morphology and re-established cell-cell contacts,
      growing into aggregates of several cells along and/or among fibers in the fabric.
      Hepatocytes were able to secrete albumin up to 14 days in culture. In vivo
      results demonstrated the biocompatibility of HYAFF-11 implanted in nude mice, in
      which hepatocytes maintained small well-organised aggregates until the 35th day.
      In conclusion, the presence of a fibroblast-secreted extracellular matrix
      improved the biological properties of the hyaluronan scaffold, favoring the
      survival and morphological integrity of hepatocytes in vitro and in vivo.

PMID- 15993943
TI  - The seasonal distribution of dissolved inorganic nitrogen and phosphorous in the
      lagoon of Venice: a numerical analysis.
AB  - This paper investigates the seasonal evolution of the spatial distributions of
      dissolved inorganic nitrogen and phosphorus, in relation to the estimation of the
      N and P loads, which were obtained in the framework of the DRAIN project. Such
      investigation is carried out by using a 3D reaction-diffusion model which has
      been calibrated against salinity data and then used for obtaining the most likely
      scenario of the spatial and seasonal distribution of DIN and DIP. The
      consequences of different management policies are also discussed, in relation to
      the current Italian legislation, which sets quality standards for both DIN and
      DIP in the lagoon of Venice.

PMID- 15993942
TI  - Expression of NADPH oxidase isoform 1 (Nox1) in human placenta: involvement in
      preeclampsia.
AB  - Increased oxidative stress in the placenta has been associated with preeclampsia
      (PE), a clinical syndrome involving placental pathology. The enzymatic sources of
      reactive oxygen species in the human placenta are as yet unidentified. We
      hypothesized that NADPH oxidase is a main source of reactive oxygen species in
      the placenta and its expression may change in PE. Employing RT-PCR, we have
      amplified a novel NADPH oxidase isoform Nox1 from human choriocarcinoma BeWo
      cells. Using polyclonal anti-peptide antiserum recognizing unique Nox1 peptide
      sequences, we identified by immunohistochemistry and cell fractionation that Nox1
      protein localizes in the BeWo cell membrane structures. Immunohistochemistry of
      normal placental tissues showed that Nox1 was localized in syncytiotrophoblasts,
      in villous vascular endothelium, and in some stromal cells. At the
      immunohistochemical level Nox1 expression was significantly increased in
      syncytiotrophoblast and endothelial cells in placentas from patients with
      preeclampsia as compared to gestational age-matched controls. Western blot
      analysis of whole placental homogenate confirmed this increase. Our data suggests
      that increased Nox1 expression is associated with the increased oxidative stress
      found in these placentas.

PMID- 15993944
TI  - Cu(II) complexation by "non-coordinating" N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid (HEPES buffer).
AB  - The combined potentiometric and spectroscopic studies of interactions of N-2
      hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) with Cu(II) demonstrated
      that this popular buffer, commonly labelled as "non-coordinating" forms a CuL+
      complex, with the logbeta(CuL) value of 3.22. This complex undergoes alkaline
      hydrolysis above pH 6, resulting in Cu(OH)2 precipitation. However, the presence
      of HEPES at a typical concentration of 100 mM at pH 7.4 elevates the apparent
      binding constant, being determined for a complex of another ligand, by a factor
      of 80. HEPES does not form ternary complexes with aminoacids Ala, Trp, and His,
      but may do so with other bioligands, such as nucleotides. Therefore, HEPES can
      still be recommended for Cu(II) studies in place of other common buffers, such as
      Tris and phosphate, but appropriate corrections and precautions should be applied
      in quantitative experiments.

PMID- 15993945
TI  - Formation of lanthanide(III) texaphyrin complexes with DNA controlled by the size
      of the central metal cation.
AB  - Interaction of lanthanide(III) texaphyrins (LnTEX) with calf thymus DNA was
      studied by UV-Vis, CD, resonance light scattering spectroscopy and by laser flash
      photolysis. The thermal stability of the LnTEX/DNA complexes decreases with the
      increasing lanthanide ion radius: LuTEX>DyTEX>GdTEX>EuTEX>CeTEX> or =LaTEX.
      Texaphyrins LaTEX, LuTEX and GdTEX produce O2(1Deltag) in methanol solutions. In
      a phosphate buffer, the concentration of O2(1Deltag) produced by these
      texaphyrins bound to DNA is affected by the formation of aggregates on the DNA
      backbone.

PMID- 15993946
TI  - Interaction centres of pyrimidine nucleotides: cytidine-5'-diphosphate (CDP) and
      cytidine-5'-triphosphate (CTP) in their reactions with tetramines and Cu(II)
      ions.
AB  - The interactions between pyrimidine nucleotides: cytidine-5'-diphosphate (CDP)
      and cytidine-5'-triphosphate (CTP) and Cu(II) ions, spermine (Spm) and 1,11
      diamino-4,8-diazaundecane (3,3,3-tet) have been studied. The composition and
      stability constants of the complexes formed have been determined by means of the
      potentiometric method, while the centres of interactions in the ligands have been
      identified by the spectral methods (UV-Vis, Ultraviolet and Visible spectroscopy;
      EPR, electron spin resonance; NMR). In the systems without metal, formation of
      the molecular complexes nucleotide-polyamine with the interaction centres at the
      endocyclic nitrogen atom of purine ring N3, the oxygen atoms of the phosphate
      group from the nucleotide and protonated nitrogen atoms of the polyamine have
      been detected. Significant differences have been found in the metallation between
      the systems with Spm and with 3,3,3-tet. In the systems with spermine, mainly
      protonated species are formed with the phosphate group of the nucleotide and
      deprotonated nitrogen atoms of the polyamine making the coordination centres,
      while the donor nitrogen atom of the nucleotide N3 is involved in the
      intramolecular interligand interactions, additionally stabilising the complex. In
      the systems with 3,3,3-tet, the MLL' type species are formed in which the oxygen
      atoms of the phosphate group and nitrogen atoms of the polyamine are involved in
      metallation, whereas the N3 atom from the pyrimidine ring of the nucleotide is
      located outside the inner coordination sphere of copper ion. The main centre of
      Cu(II) interaction in the nucleotide, both in the system with Spm and 3,3,3-tet
      is the phosphate group of the nucleotide.

PMID- 15993947
TI  - Preparative HPLC separation of methoxytetralins, ligands for melatonin receptors,
      containing two chiral centers with polysaccharide chiral stationary phases.
      Determination of enantiomeric purity.
AB  - Preparative chromatography was used to obtain approximately 200 mg of each of the
      four individual isomers of the three methoxytetrahydronaphthalenic derivatives,
      new agonist and antagonist ligands for melatonin receptors to be tested for
      binding. The mobile and stationary phases were chosen to achieve best resolution
      in shorter runtime. Enantiomeric purity was verified and quantified using normal
      and reversed phase methodology on cellulose CSPs. Enantiomer elution order was
      analysed and discussed. Limit of detection (LOD) and limit of quantification
      (LOQ) were calculated.

PMID- 15993948
TI  - Probing reward function in post-traumatic stress disorder with beautiful facial
      images.
AB  - Reward dysfunction may be implicated in post-traumatic stress disorder (PTSD).
      This study applied a behavioral probe, known to activate brain reward regions, to
      subjects with PTSD. Male heterosexual Vietnam veterans with (n = 12) or without
      (n = 11) current PTSD were administered two tasks: (a) key pressing to change the
      viewing time of average or beautiful female or male facial images, and (b) rating
      the attractiveness of these images. There were no significant group differences
      in the attractiveness ratings. However, PTSD patients expended less effort to
      extend the viewing time of the beautiful female faces. These findings suggest a
      reward deficit in PTSD.

PMID- 15993949
TI  - Brief psychiatric rating scale expanded version: How do new items affect factor
      structure?
AB  - Our goal was to suggest a factor structure for the Brief Psychiatric Rating Scale
      Expanded Version (BPRS-E) based upon a large and diverse sample and to determine
      which of the new items improved the factors derived from the 18-item version of
      the scale that have been used in clinical research for decades. We investigated
      the consistency of our proposed model over time and across demographic groups. As
      part of the Texas Medication Algorithm Project, the BPRS-E was administered to a
      total of 1440 psychiatric outpatients in three different diagnostic groups on
      multiple occasions. The sample was randomly split so that exploratory factor
      analysis could be done with the first half, and the model could be confirmed on
      the second half. A four-factor structure including factors assessing
      depression/anxiety, psychosis, negative symptoms, and activation was found. For
      each factor, we specify items in the expanded version that added to the breadth
      of the commonly used clinical factors while improving or maintaining goodness of
      fit and reliability. The final model proposed was consistent over time and across
      diagnosis, phase of illness, age, gender, ethnicity, and level of education. The
      BPRS-E has a stable four-factor structure, making it useful as a clinical outcome
      measure.

PMID- 15993950
TI  - Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor
      lysate-pulsed dendritic cell vaccine in colon cancer.
AB  - Dendritic cell (DC)-based tumor vaccine is a promising therapy for malignancies.
      Recent studies showed greater potency with DC/tumor fusion vaccines against acute
      myeloid leukemia and melanoma compared with lysate-pulsed DC vaccines. We
      compared these two vaccine strategies against murine colon cancer and
      investigated whether DC/tumor fusion cells continue to produce tumor antigens
      following fusion as a possible explanation for their increased potency. Using a
      mouse colon cancer model, CT26, we first showed that the DC/CT26 fusion vaccine
      is more effective in preventing tumor implantation than CT26 lysate-pulsed DC
      vaccine. Next, CT26 made to constitutively produce bioactive TGF-beta, a
      surrogate of tumor-derived products, was fused to DCs and found to produce
      bioactive TGF-beta 72 h after fusion. Our results suggest the DC/tumor fusion
      vaccine is more potent against colon cancer than the lysate-pulsed DC vaccine.
      These fusion cells have the distinct advantage of prolonged interaction with
      tumor antigens in vivo.

PMID- 15993951
TI  - Development of a functional cDNA array for evaluation of the Th1/Th2 balance.
AB  - The immune balance controlled by CD4(+) helper T cell subsets (T helper 1 (Th1)
      and T helper 2 (Th2)) is crucial for immunoregulation and its imbalance causes
      various immune diseases including infections, allergic disorders and autoimmune
      diseases. Therefore, it is of great importance to develop a system of diagnosing
      Th1/Th2 imbalances for curing immune diseases. Here we developed a functional
      cDNA array filter useful for assessing the Th1/Th2 balance in mice. To overcome
      the disadvantages of conventional microarrays carrying thousands of genes, we
      prepared an array filter containing 40 Th1-specific and 32 Th2-specific genes,
      which were selected from over 8700 genes based on (i) the specificity of
      expression in Th1 or Th2 cells and (ii) an expression level which is high enough
      for detection using a DNA array. This array filter provided a prompt and precise
      evaluation for the skewing of the Th1/Th2 balance combined with our calculation
      algorithm. The bias toward Th1 or Th2 was evaluated visually at a glance by
      aligning the genes on the filter. Moreover, we succeeded in evaluating the
      skewing of the Th1/Th2 balance in vivo during acute graft versus host disease
      (GVHD). Thus, this array filter will provide a novel tool for evaluation of the
      Th1/Th2 balance in a variety of immune diseases.

PMID- 15993952
TI  - Detoxication enzyme inducers modify cytokine production in rat mixed glial cells.
AB  - Pro-inflammatory cytokines, e.g. interleukin-1beta (IL-1beta), interleukin-6 (IL
      6), tumor necrosis factor-alpha (TNFalpha) as well as neurotoxic molecules such
      as nitric oxide (NO), that are produced and released by activated glial cells,
      play an important role in inflammation and oxidative stress occurring during
      Multiple Sclerosis (MS). Reduction of these processes could therefore be of
      therapeutic interest. Dimethylfumarate (DMF) and sulforaphane (SP) are well known
      for their detoxicating properties. Furthermore, they have anti-inflammatory
      effects as shown clinically by the treatment of inflammatory skin diseases.
      However, their detoxication and anti-inflammatory action on brain-derived cells
      is unknown. In the present study we have studied, within the same concentration
      range, the anti-inflammatory and detoxicating effects of DMF and SP on the
      production and release of mediators of inflammation and detoxication from
      lipopolysaccharide (LPS) activated primary co-cultures of rat microglial and
      astroglial cells. DMF and SP attenuated the LPS-induced production and release of
      TNFalpha, IL-1beta, IL-6 and NO. In addition, DMF and SP increase both mRNA level
      and activity of NAD(P)H:quinone reductase (NQO-1), a detoxication enzyme, as well
      as the cellular glutathione content. We conclude that DMF or SP simultaneously
      can (1) reduce mediators of inflammation and (2) enhance detoxication enzymes in
      LPS stimulated co-cultures of astroglial and microglial cells. This double-sided
      effect could potentially be of therapeutic interest.

PMID- 15993953
TI  - Application of GFP-tagged Plum pox virus to study Prunus-PPV interactions at the
      whole plant and cellular levels.
AB  - The Sharka disease caused by the potyvirus Plum pox virus (PPV) is one of the
      most serious viral diseases affecting stone fruit trees. The study of PPV/Prunus
      interaction under greenhouse controlled conditions is space, time, labor
      consuming. While the PPV/Prunus interactions are now quite well known at the
      whole plant level, few data however are available on the interactions between the
      virus and the Prunus host plants at the cellular level. Using a green fluorescent
      protein (GFP)-tagged M type PPV strain, combined to an in vitro inoculation
      procedure, we developed a novel tool to track PPV invasion in Prunus persica
      (peach) cv. GF305 and Prunus armeniaca (apricot) cv. Screara susceptible hosts.
      Different graft combinations were performed using in vitro-maintained healthy or
      GFP-tagged PPV infected 'GF305' and 'Screara'. Contact for 30 days in grafts
      between the inoculum and the genotype to be tested were found sufficient to allow
      the systemic spread of the recombinant virus: fluorescence from GFP-tagged PPV
      could easily be detected in the entire plant under a binocular microscope
      allowing quick and reliable sorting of infected plants. Using a fluorescence
      stereomicroscopy or confocal microscopy, GFP could also be observed in stem cross
      sections especially in epidermis and pith cells. In vitro grafting inoculation
      with GFP-tagged PPV provides a new and powerful tool to facilitate mid-term virus
      maintenance. Moreover, this tool will be of special importance in the study of
      PPV infection dynamics in Prunus, allowing as well precise observations of
      cellular events related to PPV/Prunus interactions.

PMID- 15993954
TI  - Validation and comparison of different PCR-based methods for detection of
      hepatitis B virus precore region mutants.
AB  - Hepatitis virus variants detection is useful in clinical practice; however,
      methods that are used for their identification may influence the results
      significantly. Three PCR-based assays for quantitation of G1896A precore HBV
      mutants: two allele specific PCRs, single tube (single-AS-PCR) with enzymatic
      restriction or separate tubes (twin-AS-PCR) and one oligohybridization assay (OA)
      with three probes were developed and standardized. Wild type and mutant plasmids
      and 10 sera were used as reference. All methods had sensitivity limits of
      10(4)copies/ml and their specificity encompassed 3 logs (10(4)-10(7)copies/ml)
      with dynamic ranges of logs for OA, twin-AS-PCR and single-AS-PCR, respectively.
      Single-AS-PCR and OA detected minor viral populations when their relative
      prevalence was at least 10% of the overall viral population whereas their
      detection by twin-AS-PCR ranged from 0.1 to 10% for samples with 10(7) and
      10(5)copies/ml viral loads, respectively. Twin-AS-PCR was the most sensitive to
      detect the minor viral population, whereas single-AS-PCR and OA were more
      accurate to quantify the relative proportions of the two viral populations
      independently of the overall viral load. In conclusion, an accurate
      characterization of HBV precore heterogeneity should be warranted by a careful
      choice of the most appropriate assay according to the aim of the study.

PMID- 15993955
TI  - Impact of zinc acclimation on bioaccumulation and homeostasis in Chlorella
      kesslerii.
AB  - Growth curves, cellular Zn contents and cellular protein expression were examined
      for the green alga, Chlorella kesslerii, as a function of different Zn growth
      regimes (growth in 16 pM, 1.7 nM or 1.6 microM calculated Zn2+). Zn homeostasis
      was responsible for observed differences in the capacity of the organism to
      accumulate Zn. The rapid acclimation that occurred in response to a Zn deficiency
      was likely due to the production of Zn transport sites. No differences were
      observed among cellular phytochelatin contents or efflux rate constants, although
      efflux did play an important role in regulating Zn cellular content. A long-term
      adaptation to Zn was not thought to occur since bioaccumulation and biological
      responses were similar for four successive cultures (30-40 days, 16-19 cell
      cycles) at different [Zn2+]. Among proteins that were influenced by the Zn growth
      regime, the Rubisco and histone H3 proteins were identified as being induced in
      the presence of 1.6 microM Zn2+ as compared with 1.7 nM Zn2+. The impact of the
      Zn preconditioning demonstrated that the concentrations of essential metals in
      the algal growth media would have an important, if not predominant effect on
      toxicity or bioaccumulation assessments. Furthermore, the high regulation of Zn
      transport and intracellular events by the microorganisms will likely preclude the
      use of simple metal uptake models including the free ion activity model and the
      biotic ligand model to predict either bioaccumulation or toxicological effects of
      Zn and perhaps other essential metals.

PMID- 15993956
TI  - The toxic effect of phthalate esters on immune responses of giant freshwater
      prawn (Macrobrachium rosenbergii) via oral treatment.
AB  - A previous in vitro study has indicated that four phthalate esters (PAEs) could
      damage hemocytes and decreases the cellular immunity of prawns [Sung, H.H., Kao,
      W.Y., Su, Y.J., 2003. Effects and toxicity of phthalate esters to hemocytes of
      giant freshwater prawn, Macrobranchium rosenbergii. Aquat. Toxicol. 64, 25-37].
      The aim of this study was to investigate the in vivo effect of four PAEs, diethyl
      phthalate (DEP), dihexyl phthalate (DHP), dipropyl phthalate (DPrP) and diphenyl
      phthalate (DPP) on the defense system of the giant freshwater prawn, M.
      rosenbergii. PAE dissolved in corn oil was continuously fed to prawns for 8 days
      and five immune parameters (total hemocyte count, THC; ratio of granulocytes to
      hyalinocytes, G/H; intrahemocytic total phenoloxidase activity, PO(T);
      intracellular superoxide anion (O2-) production; transglutaminase (TGase)
      activity) were separately detected on days 1, 4 and 8. In addition, mortality was
      determined on days 4 and 8 after challenging the prawns with Lactobacillus
      garvieae. In comparison with untreated prawns, the results showed that DHP
      demonstrated the lowest toxicity in that it only influenced the PO activity and
      O2- production before 4 days after treatment and caused 6.6% mortality on day 8.
      DEP decreased G/H, PO(T) and TGase activity on day 1 and reduced THC, G/H and
      PO(T) and caused 16.6% mortality on day 4; however, on day 8, it increased O2-
      production and caused no mortality. In the DPrP-treated group, a reduction of all
      the immune reactions apart from TGase activity and 22.2% mortality were detected
      on day 4. As for the effect of DPP, results showed that it decreased all the
      immune parameters apart from THC on days 1 and 4, but caused no mortality on day
      4; but on day 8, an increase of O2- production and 17.7% mortality were detected.
      These results indicated that the immune reactions of prawns were variable due to
      the different toxic effects of PAEs. In addition, it was found that, on day 8
      after treatment, the three PAEs, DHP, DPrP and DPP increased O2- production and
      did not influence the other four reactions, but mortality was detected in these
      groups. These results suggest that other physiological responses may also be
      affected to increase the susceptibility of prawns to pathogens.

PMID- 15993957
TI  - Genomic organization and effects of ivermectin selection on Onchocerca volvulus P
      glycoprotein.
AB  - Ivermectin (IVM) was first developed for use with livestock. It is now the only
      drug used for mass treatment of onchocerciasis. It is difficult to prove whether
      reports of sub-optimal responses to IVM in some Onchocerca volvulus infected
      patients are a result of drug resistance, as procedures typically used to examine
      IVM efficacy in livestock can not be performed on humans. To determine the
      effects of IVM on O. volvulus, one approach is to examine allele frequencies
      before and after treatment. Allele(s) linked to resistance may increase in
      frequency after repeated treatment. Mass treatment of large human populations to
      reduce transmission of O. volvulus will impose selection pressure for resistance.
      P-glycoprotein has been implicated as a candidate IVM resistance gene in
      nematodes. In this study, the intron-exon structure of O. volvulus P-glycoprotein
      (OvPGP) has been defined. The gene spans 10.6 kb, is AT-rich, contains 24 exons
      and a high proportion of class 0 introns. The genetic diversity of 28 loci
      spanning the entire OvPGP gene was examined in four O. volvulus populations from
      the Volta Region of Ghana. Worms collected in 1999 and 2002 from IVM treated
      patients showed reduced genetic polymorphism and an increase in the number of
      loci not in Hardy-Weinberg equilibrium. Changes in allelic patterns and a
      reduction in diversity at many loci in P-glycoprotein in the parasites from IVM
      treated patients in 1999 and 2002 suggest that IVM is imposing selection on this
      gene, consistent with a possible development of IVM resistance.

PMID- 15993958
TI  - Evaluation of endogenous reference genes for real-time PCR quantification of gene
      expression in Ancylostoma caninum.

PMID- 15993959
TI  - Synergistic activation of the insulin gene promoter by the beta-cell enriched
      transcription factors MafA, Beta2, and Pdx1.
AB  - Specific expression of the insulin gene in pancreatic islet beta-cells requires
      multiple cis-regulatory elements in its promoter. Pdx1, MafA, and Beta2 have been
      identified as beta-cell enriched transcription factors that bind to these
      elements. Pdx1 has been shown to bind to A1, A3, A5, and GG2, and Beta2 binds to
      E1 by forming a heterodimer with the ubiquitous factor E47. MafA was recently
      identified as a C1-element binding factor. However, interactions between these
      factors and the promoter have not been characterized in detail. In this report,
      we show that these transactivators synergistically stimulate insulin promoter
      activity. Among multiple binding sites for Pdx1, MafA, and Beta2, at least GG2,
      C1, and E1 elements located in the promoter region between -150 and -100 base
      pairs are necessary for the synergism. We also found that neither MafB nor c-Maf,
      close relatives of MafA, showed synergistic activation. These results suggest
      that co-expression and functional synergism of these beta-cell enriched
      transactivators, MafA, Pdx1, and Beta2, are critical for establishing the beta
      cell-specific and efficient expression of the insulin gene.

PMID- 15993960
TI  - Patients strategies for managing medication for chronic heart failure.
AB  - OBJECTIVES: To explore patients views of the management of medication of chronic
      heart failure (CHF); to explore in what circumstances they have difficulties in
      managing medication. DESIGN: Qualitative analysis of in-depth interviews using a
      constant comparative approach. PARTICIPANTS: Patients attending an outpatients
      clinic with a primary diagnosis of CHF due to left ventricular systolic
      dysfunction, NYHA Class II or III symptoms, and a history of hospital admission
      for heart failure. RESULTS: 50 patients were recruited, average age 67.1 years
      with ranges between 41 and 80 years. 26 were classified as NYHA Class II and 24
      Class III. Patients reported developing routines and back up strategies to help
      with the complex task of medication-taking. They also described circumstances in
      which they were more likely not to take medication. CONCLUSIONS: This study
      demonstrates, with a large sample of respondents, the complexities of medication
      taking and the difficulties of maintaining constant medication over a long period
      of time. The study provides examples of patients' strategies for so doing. Health
      care professionals should recognise that concordance may vary but explore ways in
      which they can help patients establish routines.

PMID- 15993961
TI  - An unusual right-sided endocarditis: a case report of eustachian valve
      endocarditis.

PMID- 15993962
TI  - Predictive factors of cardiac events after implantation of sirolimus-eluting
      stents for treatment of in-stent restenosis.
AB  - BACKGROUND: The factors associated with recurrent restenosis after SES
      implantation for in-stent restenosis are unknown. This study aimed to assess the
      clinical outcome and to analyse predictive factors of cardiac events in patients
      with in-stent restenosis treated with Sirolimus-eluting stent (SES). METHODS: In
      3 centers, consecutive patients (n = 100) with elective indication to
      percutaneous coronary intervention (PCI) for in-stent restenosis (n = 110) were
      treated with SES: 28 lesions were focal, 40 diffuse, 17 proliferative, and 15
      showed total occlusion. RESULTS: SES implantation was successful in all patients,
      without complication during the first hospital stay. The mean follow-up was 15
      (10-24) months. A cardiac event related to the target vessel occurred in 24 (24%)
      patients, and was associated with dialysis status (p < 0.05), lower ejection
      fraction (p < 0.05) and revascularization without SES in another site (p <
      0.0001). A cardiac event related to the SES occurred in 11 (11%) patients,
      secondary to an acute or sub-acute thrombosis of the SES (2%), to a late
      occlusion of the target vessel (4%) or to a non-occlusive restenosis of the SES
      (5%), and was associated with unstable angina (p < 0.01), multivessel disease (p
      < 0.03) and revascularization without SES in another site (p < 0.03). No cardiac
      event related to the SES occurred in patients with direct stenting. Target lesion
      revascularization for in-SES restenosis or occlusion of the target vessel was
      performed in 7 (7%) patients, and was associated with unstable angina (p < 0.01)
      and revascularization without SES in another site (p < 0.01). Target vessel
      revascularization was needed in 20 patients (20%), related to dialysis status (p
      < 0.01) and a revascularization without SES in another site (p < .0001).
      CONCLUSIONS: SESs are effective in the treatment of high risk patients with
      complex in-stent restenosis. Most of cardiac events during follow-up are related
      to a revascularization without SES in another site.

PMID- 15993963
TI  - Spatial relationship between Mycobacterium bovis strains in cattle and badgers in
      four areas in Ireland.
AB  - We investigated whether strains (restriction fragment length polymorphism, RFLP
      types) of Mycobacterium bovis isolated from badgers and from cattle clustered
      among and within four areas in Ireland. The spatial scan test and nearest
      neighbor analysis were used as the spatial cluster-detection techniques. In
      addition, for each of the major strains, associations between the distance to
      badger setts and the "centroid" of the cattle farm were assessed in a logistic
      model. Overall, between September 1997 and May 2000, 316 and 287 M. bovis
      samples, from badgers and cattle, respectively, were strain-typed. The
      distribution of strains in badgers, and separately in cattle, differed among
      areas. Within each of the four large areas, badgers and cattle tended to have
      similar strains; this is consistent with the sharing of M. bovis strains within
      an area. In more detailed within-area analyses, some spatial clusters of M. bovis
      strains were detected, separately, in both cattle and badgers. Almost half of the
      infected badger setts with a specific strain were located outside of the
      "detected" clusters. There was no association between the number of infected
      badgers with a specific M. bovis strain within 2 or 5 km distances to cattle
      herds, and the risk of the same strain in cattle. We speculate about the dynamic
      nature of badger movements, as an explanation for the absence of more clusters of
      most of the strains of M. bovis isolated from badgers, and its impact on trying
      to study transmission of M. bovis between cattle and badger.

PMID- 15993964
TI  - From emotion perception to emotion experience: emotions evoked by pictures and
      classical music.
AB  - Most previous neurophysiological studies evoked emotions by presenting visual
      stimuli. Models of the emotion circuits in the brain have for the most part
      ignored emotions arising from musical stimuli. To our knowledge, this is the
      first emotion brain study which examined the influence of visual and musical
      stimuli on brain processing. Highly arousing pictures of the International
      Affective Picture System and classical musical excerpts were chosen to evoke the
      three basic emotions of happiness, sadness and fear. The emotional stimuli
      modalities were presented for 70 s either alone or combined (congruent) in a
      counterbalanced and random order. Electroencephalogram (EEG) Alpha-Power-Density,
      which is inversely related to neural electrical activity, in 30 scalp electrodes
      from 24 right-handed healthy female subjects, was recorded. In addition, heart
      rate (HR), skin conductance responses (SCR), respiration, temperature and
      psychometrical ratings were collected. Results showed that the experienced
      quality of the presented emotions was most accurate in the combined conditions,
      intermediate in the picture conditions and lowest in the sound conditions.
      Furthermore, both the psychometrical ratings and the physiological involvement
      measurements (SCR, HR, Respiration) were significantly increased in the combined
      and sound conditions compared to the picture conditions. Finally, repeated
      measures ANOVA revealed the largest Alpha-Power-Density for the sound conditions,
      intermediate for the picture conditions, and lowest for the combined conditions,
      indicating the strongest activation in the combined conditions in a distributed
      emotion and arousal network comprising frontal, temporal, parietal and occipital
      neural structures. Summing up, these findings demonstrate that music can markedly
      enhance the emotional experience evoked by affective pictures.

PMID- 15993966
TI  - Seizure-induced changes of mineralocorticoid and glucocorticoid receptors in the
      hippocampus in seizure sensitive gerbils.
AB  - Abnormal corticosteroid hormone levels during stress and resultant
      mineralocorticoid receptor (MR)/glucocorticoid receptor (GR) imbalance enhance
      the vulnerability of specific hippocampal neurons. In the present study, we
      investigated the distribution of MR and GR in seizure resistant (SR) and seizure
      sensitive (SS) gerbils, and observed the seizure-induced changes of MR and GR in
      the hippocampus of SS gerbils using immunohistochemistry and western blot
      analysis. MR and GR immunoreactivities were higher in the SS pre-seizure gerbils
      than that in SR gerbils. In the SR gerbils, the immunodensity of GR was high
      compared to that of MR. The changes of MR and GR immunoreactivities were
      significant in the stratum pyramidale of the hippocampal CA1 region and the
      infrablade of the dentate gyrus after seizure on-set. MR immunoreactivity in the
      CA1 region was significantly increased at 12h after seizure on-set, thereafter MR
      immunoreactivity was decreased. MR immunoreactivity in the dentate gyrus was
      decreased time-dependently after seizure on-set. GR immunoreactivity was
      decreased in the CA1 region and dentate gyrus time-dependently after seizure on
      set. At 12h after seizure on-set, differences in MR and GR immunodensity
      diminished in the CA1 region and dentate gyrus. This imbalance of MR and GR
      immunoreactivity in these regions may be associated with seizure generation in
      the Mongolian gerbil, which is a hereditary seizure model.

PMID- 15993967
TI  - Prevalence and location of Listeria monocytogenes in farmed rainbow trout.
AB  - A total of 510 rainbow trout originating from fish farms in lakes and sea areas
      around Finland were studied for the presence of Listeria monocytogenes. Samples
      were studied as pools from five fish. Gill, viscera, and skin from the pooled
      samples were analysed separately. The individual samples were analysed later if
      the pooled sample was found to be Listeria positive. The prevalence of Listeria
      spp. and L. monocytogenes in pooled unprocessed fresh rainbow trout was on
      average 35.0% and 14.6%, respectively. On the other hand, the prevalence of
      Listeria spp. and L. monocytogenes in individual thawed fish was found to be
      14.3% and 8.8%, respectively. These numbers tend to overestimate and
      underestimate the real situation because not all fish in pooled samples were
      necessarily contaminated and in some of the Listeria positive pooled samples all
      individual samples turned out to be Listeria free. The prevalence of L.
      monocytogenes varied greatly between different fish farms from zero to 100% in
      pooled samples and from zero to 75% according to individually studied fish
      samples. Some indications of the influence of weather conditions and seasonal
      variations that strongly affected the Listeria contamination of fish were also
      noticed. The location of Listeria spp. and L. monocytogenes in different parts of
      the fish differed with statistical significance in rainbow trout. Up to 95.6% of
      the L. monocytogenes and 84.5% of Listeria spp. positive samples were gill
      samples. Only 4.4% (2/45) of the L. monocytogenes positive samples were obtained
      from skin or viscera. Closer study at one fish farm revealed that there was only
      one L. monocytogenes ribotype present in the contaminated fish, although water
      and surfaces were heavily contaminated with six other L. monocytogenes ribotypes.

PMID- 15993965
TI  - The sarcoglycan-sarcospan complex localization in mouse retina is independent
      from dystrophins.
AB  - The sarcoglycan-sarcospan (SG-SSPN) complex is part of the dystrophin
      glycoprotein complex that has been extensively characterized in muscle. To
      establish the framework for functional studies of sarcoglycans in retina here, we
      quantified sarcoglycans mRNA levels with real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) and performed immunohistochemistry to
      determine their cellular and subcellular distribution. We showed that the beta-,
      delta-, gamma-, epsilon-sarcoglycans and sarcospan are expressed in mouse retina.
      They are localized predominantly in the outer and the inner limiting membranes,
      probably in the Muller cells and also in the ganglion cells axons where the
      expression of dystrophins have never been reported. We also investigated the
      status of the sarcoglycans in the retina of mdx(3cv) mutant mice for all Duchene
      Muscular Dystrophy (DMD) gene products. The absence of dystrophin did not produce
      any change in the sarcoglycan-sarcospan components expression and distribution.

PMID- 15993968
TI  - Functional periplasmic secretion of organophosphorous hydrolase using the twin
      arginine translocation pathway in Escherichia coli.
AB  - Recombinant Escherichia coli systems expressing organophosphorous hydrolase (OPH)
      have been proposed for biotransformation of toxic organophosphate compounds.
      However, whole cell biocatalyst systems are critically disadvantaged due to
      substrate diffusion limitations. To enhance whole cell biocatalytic efficiency,
      we engineered E. coli, for the first time, to secrete metal ion cofactor
      requiring OPH into the periplasmic space using the twin-arginine translocation
      (Tat) pathway. In particular, the twin-arginine signal sequence of E. coli
      trimethylamine N-oxide (TMAO) reductase (TorA) was employed. Even though total
      OPH activity in the cell lysate fraction was lower in the periplasmic-secreting
      strain than in the control cytosolic-expressing strain, whole cell OPH activity
      was approximately 2.8-fold higher due to successful translocation of OPH into the
      periplasmic space. In addition, whole cell OPH activity in the periplasmic
      secreting strain was far more stable than that in the cytosolic-expressing
      strain. Therefore, Tat-driven periplasmic-secreting E. coli can be successfully
      employed as efficient whole cell biocatalysts.

PMID- 15993969
TI  - Morphological studies of oligodeoxyribonucleotides probes covalently immobilized
      at polystyrene modified surfaces.
AB  - The immobilization of short ss-DNA (18- and 36-mer) and their hybridization were
      studied at gold and glassy carbon substrates modified with low molecular weight
      (approximately 12, 18 and 24 kg/mol) polystyrene thin films. Amino-modified DNA
      was attached to the surface by reaction with succinimide ester groups bound to
      the polystyrenes. A ferrocene modified DNA target was used to confirm the probe
      target hybridization. Atomic force microscopy studies showed significant
      morphological changes after probe immobilization and hybridization compared to
      the featureless structure of the polystyrene film. Single-stranded DNA samples
      had a globular morphology with an average density of 3.8 and 2.2 (x 10(11))
      globules/cm2 for the 18- and 36-mer, respectively. The formation of a porous
      structure with a 2.0 and 1.0 (x10(11)) average pore density corresponding to the
      18- and 36-mer was observed after hybridization. A surface composition analysis
      was done by X-ray photoelectron spectroscopy to confirm and support the images
      interpretation. Ferrocene oxidation (+323 mV/18-mer, +367 mV/36-mer, versus
      Ag/AgCl) proved the presence of ds-DNA at the modified surfaces.

PMID- 15993970
TI  - Differentiation of four Aspergillus species and one Zygosaccharomyces with two
      electronic tongues based on different measurement techniques.
AB  - Two electronic tongues based on different measurement techniques were applied to
      the discrimination of four molds and one yeast. Chosen microorganisms were
      different species of Aspergillus and yeast specie Zygosaccharomyces bailii, which
      are known as food contaminants. The electronic tongue developed in Linkoping
      University was based on voltammetry. Four working electrodes made of noble metals
      were used in a standard three-electrode configuration in this case. The St.
      Petersburg electronic tongue consisted of 27 potentiometric chemical sensors with
      enhanced cross-sensitivity. Sensors with chalcogenide glass and plasticized PVC
      membranes were used. Two sets of samples were measured using both electronic
      tongues. Firstly, broths were measured in which either one of the molds or the
      yeast grew until late logarithmic phase or border of the stationary phase. Broths
      inoculated by either one of molds or the yeast was measured at five different
      times during microorganism growth. Data were evaluated using principal component
      analysis (PCA), partial least square regression (PLS) and linear discriminant
      analysis (LDA). It was found that both measurement techniques could differentiate
      between fungi species. Merged data from both electronic tongues improved
      differentiation of the samples in selected cases.

PMID- 15993972
TI  - High level expression of functionally active human lactoferrin in silkworm
      larvae.
AB  - In this paper, recombinant human lactoferrin (rhLf) was expressed very well using
      Bombyx mori nuclear polyhedrosis baculovirus expression system. Infection of
      silkworm larvae with recombinant virus, vBm-hLf, the rhLf was efficiently
      secreted into larvae hemolymph and the concentration of product purified was
      about 65 microg/ml. The isolated rhLf molecular mass was approximately 78 kDa,
      lower than that of the human lactoferrin (hLf) standards, which may be due to
      incomplete glycosylation or protein degradation. Furthermore, the rhLf was
      characterized and its biological activities were evaluated by in vivo bioassay
      using dextran sodium sulfate (DSS)-induced colitis mouse model that mimics some
      characteristics of colitis disease in human. We conclude that silkworm expression
      system can be used successfully to express functional human lactoferrin.

PMID- 15993971
TI  - A fast and flexible PEG-mediated transient expression system in plants for high
      level expression of secreted recombinant proteins.
AB  - Plant expression systems offer a valuable alternative to traditional systems for
      the production of recombinant biopharmaceuticals. A highly efficient
      polyethyleneglycol (PEG)-mediated transient expression system for secreted
      recombinant proteins in plants has been developed. The human vascular endothelial
      growth factor 121 (rhVEGF) has been successfully expressed and efficiently
      secreted into the culture medium by transiently transformed moss protoplasts. In
      order to obtain secretion efficiency data, different expressed signal peptides
      were analysed and time course studies were performed with expression constructs
      containing different promoters. The transformation procedure was optimised for
      high level expression (up to 10 microg/ml) and successfully performed even with a
      transgenic glyco-engineered strain lacking plant-specific immunogenic sugar
      residues in N-glycans. The amount of rhVEGF was produced in such quantity that it
      allowed for the analysis of biological activity, silver-staining and Western
      blotting, revealing the correct formation and processing of the homodimer. This
      fast and flexible transient expression system enables feasibility studies and
      construct optimisation to be concluded within a few days, thus avoiding the time
      consuming step of having to generate stably transformed lines.

PMID- 15993973
TI  - The glycosylation pattern of baculovirus expressed envelope protein E2 affects
      its ability to prevent infection with bovine viral diarrhoea virus.
AB  - We have investigated the role of glycosylation of the envelope glycoprotein E2 of
      bovine viral diarrhoea virus (BVDV), produced in insect cells, in BVDV infection.
      When amino acids predicated to code for the C-terminal N-linked glycosylation
      site were mutated the resulting protein was less efficient than wild type protein
      at preventing infection of susceptible cells with BVDV. In addition, mutational
      analysis showed that a further two predicted N-terminal N-linked glycosylation
      sites of E2 are required for efficient production of recombinant protein.

PMID- 15993974
TI  - Molecular analysis of the NS3/NS3A gene of Bluetongue virus isolates from the
      1979 and 1998-2001 epizootics in Greece and their segregation into two distinct
      groups.
AB  - The sequence of the genome segment 10 (Seg-10) encoding NS3/NS3A was determined
      for 19 field isolates of Bluetongue virus (BTV) of serotypes BTV-1, BTV-4, BTV-9
      and BTV-16, derived from epizootics in Greece in the years 1979 and 1998-2001.
      The aim of the study was to define the molecular epidemiology of the virus in
      this part of the Mediterranean basin. On the basis of the Seg-10 sequences, the
      isolates grouped into two distinct phylogenetic clusters. These were Greek group
      I of solely serotype BTV-4 viruses, and Greek group II of serotypes BTV-1, BTV-9
      and BTV-16 viruses. The isolates in Greek group I clustered with the Corsican and
      Tunisian BTV-2 serotypes and US group II strains of BTV-10 and BTV-13 serotypes,
      while those in Greek group II with Chinese, Indian and Australian viruses of
      different serotypes suggesting that viruses derived from two distinct ecosystems
      have caused BT incursions in Greece over the last 25 years. The NS3/NS3A
      sequences of most of the BTV-4 isolates were identical, irrespective of the year
      of isolation, geographical location and host species or tissue origin. Maximum of
      15-16% nucleic acid sequence variation, but only 4% deduced amino acid
      substitution, were observed between groups I and II. Furthermore, the clustering
      of the NS3/NS3A sequences was independent of the viral serotype, indicating the
      occurrence of genome segment reassortment during the course of evolution of the
      viruses.

PMID- 15993975
TI  - Bioavailability of nerodilol-based transdermal therapeutic system of nicorandil
      in human volunteers.
AB  - The objective of the present investigation was to design and evaluate a nerodilol
      based transdermal therapeutic system (TTS) for finding its ability in providing
      the desired steady-state plasma concentration of nicorandil in human volunteers.
      The influence of EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive
      coated EVA2825-rat skin composite on the in vitro permeation of nicorandil from a
      nerodilol-based HPMC gel drug reservoir was studied against a control (excised
      rat skin alone). The flux of nicorandil from the nerodilol-based HMPC drug
      reservoir across excised rat skin (control) was 384.0+/-4.6 microg/cm2 h and this
      decreased to 222.7+/-7.1 microg/cm2 h when studied across EVA2825 membrane
      indicating that EVA2825 membrane was effective as rate controlling membrane. The
      flux of the drug decreased to 183.8+/-5.7 microg/cm2 h on application of a water
      based acrylic adhesive (TACKWHITE A 4MED) coat to EVA2825 membrane. However, the
      flux of nicorandil across adhesive-coated EVA2825-membrane-rat-skin composite was
      164.8+/-1.8 microg/cm2 h, which was 1.74-times of the required flux that prompted
      for preparation of TTS. The nerodilol-based drug reservoir system was sandwiched
      between a composite of adhesive-coated EVA2825 membrane-release liner and a
      backing membrane. The resultant sandwich was heat-sealed to produce circle-shaped
      TTS (20 cm2) that were subjected to bioavailability study in human volunteers
      against immediate release nicorandil tablet. The nerodilol-based TTS provided a
      steady-state plasma concentration of 25.5 ng/ml for 24 h in human volunteers. It
      was concluded that the nerodilol-based TTS of nicorandil provided the desired
      plasma concentration of the drug for the predetermined period of time with
      minimal fluctuations.

PMID- 15993976
TI  - [Treatment of heterotopic ossification by extracorporeal shock wave: 26
      patients].
AB  - OBJECTIVES: To evaluate the effects of extracorporeal shockwave therapy (ESWT) on
      heterotopic ossification leading to functional limitations in the short and
      medium term. METHODS: Twenty-six patients with heterotopic ossification received
      sessions of ESTW (4000 shocks, 3/s), with an energy ranging from 0.54 to 1.06
      mJ/mm2, once a week for 4 consecutive weeks. Intermediary assessments performed 1
      month after the last session related to pain (on a visual analog scale [VAS]),
      range of motion, functional independence (FIM), walking distance (whenever
      possible), radiology, and blood calcium and alkaline phosphatase levels. Eighteen
      patients with total hip arthroplasty (THA) were followed up by quiz, at 11
      months, on average. RESULTS: Heterotopic ossification was neurogenic in 5
      patients and nonneurogenic in 21. The length of evolution of ossification was
      32+/-21 months. The measurements showing significant improvement in the short
      term were pain, with a mean decrease of 4.32 to 1.14 on a VAS; joint flexion,
      with an mean increase of 8.18+/-11.9 degrees; and walking distance, with a mean
      increase from 1126 to 2776 m. The treatment was tolerated for the most part. THA
      cases showed a decline in factors initially shown to be improved. However, the
      long-term results were superior to clinical status before treatment. CONCLUSION:
      ESWT might be an interesting treatment for heterotopic ossification and can be a
      complement to usual medical treatment, physiotherapy, and before surgery.

PMID- 15993977
TI  - [C-reactive protein, leukocyte count and D-dimer monitoring after orthopedic
      surgery: early diagnosis of infectious or thromboembolic complications. Part two:
      does d-dimer measurement contribute to the diagnosis of postoperative venous
      thromboembolism?].
AB  - OBJECTIVES: To determine the modification in postoperative D-dimer level as a
      function of the surgical act and to assess the relevance of this measure for
      diagnosing thromboembolism. METHOD: A cohort of 179 patients was followed: group
      1 comprised 128 patients undergoing lower limb arthroplasty, group 2 comprised 29
      patients undergoing lower limb surgery without implant, and group 3 comprised 22
      patients undergoing spinal or upper limb surgery. D-dimer level was
      systematically measured on admission and then once a week for 4 weeks. Doppler
      ultrasonography was performed on clinical suspicion of deep vein thrombosis. D
      dimer levels were compared between patients with and without deep vein
      thrombosis. RESULTS: D-dimer levels were constantly elevated postsurgery (2- to 6
      fold above normal) and returned to normal by week 4 in groups 2 and 3 but
      remained elevated in group 1 (3-fold above normal). Deep vein thrombosis was
      suspected in 45 cases and confirmed by Doppler ultrasonography in 10 cases. D
      dimer level was not significantly different between patients with deep vein
      thrombosis and those without. DISCUSSION AND CONCLUSIONS: In the postoperative
      period, measurement of D-dimer level does not aid in diagnosing thromboembolism
      since its constant high level obviates any negative predictive value.

PMID- 15993978
TI  - Direct access in primary care and patient satisfaction: a European study.
AB  - OBJECTIVE: This study addressed the question to what extent gate-keeping or
      direct access to health care services influences the satisfaction with GP
      services by the population in 18 European countries ("old" EU-countries plus
      Norway, Iceland and Switzerland). METHODS: Two datasets were collected. Firstly,
      country experts were asked to indicate for 17 different health care providers
      whether they were directly accessible. A direct accessibility scale was computed
      from the percentage of services that were directly accessible. Secondly, for
      patient satisfaction the EUROPEP study was used. This dataset contained
      information about patient satisfaction with general practitioners services in 14
      European countries. RESULTS: If more health care providers were directly
      accessible in a country, patients showed a higher satisfaction with general
      practice than in countries where more referrals were required (Pearson's r =
      0.54, p = 0.05). Satisfaction with organisational aspects of general practice
      (concerning amongst others waiting time and possibilities to make appointments)
      correlates significantly with a high score on our direct accessibility measure
      (Pearson's r = 0.67, p = 0.01). Satisfaction with patient physician communication
      (Pearson's r = 0.46, p = 0.10) and medical technical content of the care
      (Pearson's r = 0.41, p = 0.14) are not influenced by direct accessibility.
      CONCLUSIONS: Direct accessibility appeared to be important for patients.
      Apparently, if patients have freedom of choice for the type of health care
      provider, they evaluate the GP-services more positively. However, this mainly
      concerns satisfaction with organisational aspects of GP-services; the
      accessibility does not influence patient's judgement about the actual care
      provided by their GP.

PMID- 15993979
TI  - Development of a deterministic XML schema by resolving structure ambiguity of HL7
      messages.
AB  - Health level 7 (HL7) is a standard for medical information exchange. It defines
      data transfers for the application systems in the healthcare environment.
      Alternatively, the extensible markup language (XML) is a standard for data
      exchange using the Internet. If exchange messages follow the content and the
      sequence defined by HL7 and are expressed in the XML format, the system may
      benefit from the advantages of both standards. In creating the XML schema, we
      found ambiguities in HL7 message structures that cause the XML schema to be non
      deterministic. These ambiguous expressions are summarized within 12 structures
      and can be replaced with equivalent or similar unambiguous structures. The finite
      state automata are used to verify expression equivalence. Applying this schema,
      an XML document may eliminate redundant segment group definitions and make the
      structure simple and easy to reproduce. In this paper, we discuss the methods and
      our experience in resolving ambiguous problems in HL7 messages to generate a
      deterministic XML schema.

PMID- 15993980
TI  - The retinoid X receptor agonist bexarotene (Targretin) synergistically enhances
      the growth inhibitory activity of cytotoxic drugs in non-small cell lung cancer
      cells.
AB  - This study was designed to evaluate, using preclinical models of non-small cell
      lung cancer (NSCLC), the growth inhibitory effects of the retinoid X receptor
      (RXR) agonist bexarotene (LGD1069, Targretin) in combination with cytotoxic
      agents currently used as standard first-line therapy in advanced disease.
      Although single-agent bexarotene had modest growth inhibitory effects in several
      cell lines, efficacy was observed only in the micromolar range (>1muM), which
      approximates the plasma C(max) measured in pharmacokinetic studies in patients.
      However, when combined with paclitaxel or vinorelbine, bexarotene produced a
      concentration-dependent enhancement of the growth inhibitory activities of
      paclitaxel and vinorelbine. Formal synergy analysis using the Calu3 cell line
      demonstrated that the combination of bexarotene with either cytotoxic agent
      produced synergistic activity (combination index, CI<1). The in vitro
      observations were confirmed in vivo in a NSCLC xenograft tumor model (Calu3),
      where both bexarotene/paclitaxel and bexarotene/vinorelbine combinations produced
      significantly greater antitumor effects than the single agents. These results
      demonstrate that bexarotene can cooperate with widely used cytotoxic agents to
      decrease the growth of NSCLC tumor cells both in vitro and in vivo, and suggest
      the potential benefit of adding a RXR-selective agonist in combination with
      chemotherapy for NSCLC treatment. Furthermore, the data support the clinical
      observation from phase I/IIa trials suggesting that bexarotene has beneficial
      effects on survival when used in combination with cytotoxic agents in advanced
      NSCLC.

PMID- 15993981
TI  - Front-line treatment of advanced non-small cell lung cancer with irinotecan and
      docetaxel: a multicentre phase II study.
AB  - PURPOSE: To evaluate the efficacy and tolerance of the irinotecan plus docetaxel
      combination in patients with advanced non-small cell lung cancer (NSCLC).
      PATIENTS AND METHODS: Thirty-nine chemotherapy-naive patients with advanced NSCLC
      were treated with irinotecan 200mg/m2 followed by docetaxel 80 mg/m2
      intravenously on day 1 with granulocyte colony-stimulating factor (150 microg/m2)
      support from day 2 to 9. Treatment was repeated every 3 weeks. RESULTS: A partial
      response was achieved in 9 (23%; 95% confidence interval 9.85-36.3%) patients;
      stable and progressive disease were observed in 10 (25.6%) and 20 (51.4%)
      patients, respectively. The median duration of response was 7.1 months and the
      median time to tumor progression 3 months. The median survival time was 10.8
      months and the 1-year survival 42.2%. Four (10.3%) patients developed grade 4
      neutropenia and all but one were complicated with fever; there was no treatment
      related death. Nine (23.1%) patients developed grade 3 or 4 diarrhea while grade
      2 or 3 fatigue occurred in nine (23.1%), and grade 3 mucositis in two (2.6%).
      CONCLUSION: The combination of irinotecan/docetaxel is a relatively active non
      platinum-based chemotherapy regimen with manageable toxicity, which could be
      given in an outpatient basis; this regimen merits to be further studied in order
      to improve its tolerance and evaluate its clinical relevance in patients who can
      not tolerate platinum-based doublets.

PMID- 15993982
TI  - Angiotensin II and III upregulate body fluid volume of the clam worm Perinereis
      sp. via angiotensin II receptors in different manners.
AB  - Angiotensin III (Ang III) as well as angiotensin II (Ang II) suppressed body
      weight loss of the clam worm Perinereis sp. under a hyper-osmotic condition, and
      enhanced body weight gain under a hypo-osmotic condition. Under a drying
      condition where the water inflow from outside the body was eliminated, Ang II
      suppressed body weight loss, but Ang III did not. Under these conditions,
      angiotensins I, IV, and (1-7) had no effect, and saralasin blocked the effects of
      Ang II and Ang III. It is concluded that Ang II and Ang III upregulate body fluid
      volume of the clam worm via Ang II receptors in different ways.

PMID- 15993983
TI  - Melanocortin-4 receptor-null mice display normal affective licking responses to
      prototypical taste stimuli in a brief-access test.
AB  - We tested whether MC4R null mice display altered gustatory function relative to
      wild-type controls that may contribute to the characteristic hyperphagia and
      obesity associated with this gene deletion. Mice were tested for their licking
      responses to prototypical taste solutions (sucrose, NaCl, quinine, citric acid)
      in series of daily 30-min sessions in which a range of concentrations of each
      tastant was available in randomized blocks of 5-s trials. Notwithstanding some
      minor deviations, the concentration-response functions of the MC4R null and wild
      type mice were basically the same for all of the prototypical compounds tested
      here. Thus, taste-based appetitive and avoidance behavior is expressed in the
      absence of the MC4 receptor, demonstrating that this critical component in the
      melanocortin system is not required for normal affective gustatory function to be
      maintained.

PMID- 15993984
TI  - The cAMP-specific phosphodiesterase 4B mediates Abeta-induced microglial
      activation.
AB  - Microglial activation is a key player in the degenerative process that
      accompanies the deposition of amyloid-beta (Abeta) peptide into senile plaques in
      Alzheimer's disease (AD) patients. The goal of this study is to identify novel
      genes involved in microglial activation in response to Abeta peptide. Prompted by
      the fact that soluble Abeta(1-42) (sAbeta(1-42))-stimulated primary rat microglia
      produce more tumor necrosis factor-alpha (TNF-alpha) than fibrillar Abeta(1-42)
      (fAbeta(1-42))-stimulated microglia, we examined gene expression in these cells
      following stimulation using cDNA arrays. This analysis confirms the upregulation
      caused by both sAbeta(1-42) and fAbeta(1-42) of pro-inflammatory molecules such
      as TNF-alpha, interleukin-1beta and macrophage inflammatory protein-1alpha. In
      addition, other transcripts not previously described in the context of Abeta
      induced microglial activation were identified. The modulation of some of these
      genes within microglial cells seems to be specific to sAbeta(1-42) as compared to
      fAbeta(1-42) suggesting that different forms of Abeta may activate distinct
      pathways during the progression of AD. Importantly, we demonstrate that Pde4B, a
      cAMP-specific phosphodiesterase, is upregulated by Abeta and results in an
      increased production of TNF-alpha. Inhibition of Pde4B reduces by up to 70% the
      release of TNF-alpha from sAbeta-stimulated microglial cells, implicating cAMP as
      an important mediator of Abeta-induced microglial activation.

PMID- 15993985
TI  - Associative and motor learning in 12-month-old transgenic APP+PS1 mice.
AB  - Doubly transgenic 12-month-old amyloid precursor protein and presenilins 1
      (APP+PS1) mice (n=14) and littermate control mice (n=17) were tested on eyeblink
      classical conditioning-a task impaired in humans with Alzheimer's disease (AD).
      Mice were also tested on a motor learning task (rotorod) and on sensory tasks
      (prepulse inhibition [PPI] and acoustic startle). Transgenic mice had impaired
      motor performance on rotorod. Overall, APP+PS1 mice performed similarly to
      controls on both 500ms delay and 500ms trace eyeblink conditioning as well as on
      prepulse inhibition (PPI) and acoustic startle. However, within the transgenic
      group, cortical amyloid burden correlated significantly with decreased trace
      eyeblink conditioning. Moreover, cortical amyloid burden and hippocampal
      microglia activation correlated significantly with decreased PPI. These data
      suggest that only those transgenic mice with the most severe amyloid pathology
      exhibited deficits in hippocampus-dependent tasks. Transgenic mouse models of
      amyloid deposition differ from Alzheimer patients not only by the absence of
      major neuronal loss, but also by the general absence of severe impairments in
      eyeblink conditioning, except for mice with the greatest amyloid pathology.

PMID- 15993986
TI  - Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid
      peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's
      disease.
AB  - Previous studies show increased levels of lipid peroxidation and neurotoxic by
      products of lipid peroxidation including 4-hydroxynonenal (HNE) and acrolein in
      vulnerable regions of the Alzheimer's disease (AD) brain. To determine if lipid
      peroxidation occurs early in progression of AD, we analyzed levels of HNE and
      acrolein in the hippocampus/parahippocampal gyrus (HPG), superior and middle
      temporal gyrus (SMTG) and cerebellum (CER) of 7 subjects with Mild Cognitive
      Impairment (MCI), six subjects with early AD (EAD) and sevem age-matched control
      subjects using liquid chromatography electrospray ionization tandem mass
      spectrometry (LC/ESI/MS/MS). Our data show that there is a statistically
      significant (P<0.05) increase in HNE in HPG, SMTG and CER in MCI compared to age
      matched control subjects. Specimens of SMTG also showed a significant increase in
      levels of acrolein in MCI. Comparison of EAD and control subjects showed a
      statistically significant increase in HNE in HPG and SMTG and a significant
      increase in acrolein in all three brain regions studied. We did not observe any
      statistically significant differences between MCI and EAD specimens. These
      results suggest that lipid peroxidation occurs early in the pathogenesis of AD.

PMID- 15993987
TI  - Induction of vascular amyloidosis-beta by oxidative stress depends on APOE
      genotype.
AB  - The reduced antioxidant defense in apolipoprotein E epsilon4/epsilon4 carriers
      may contribute to beta-amyloidosis. Previously we found that Fe(2+)-induced
      oxidative stress caused greater protein oxidation in epsilon4/epsilon4 than in
      epsilon3/epsilon3 human brain vascular smooth muscle cells. Moreover, Fe(2+)
      induced lysosomal accumulation of endogenous Abeta and APOE in cultured cells,
      and Abeta deposition in vascular tunica media in organotypic cultures of brain
      vessels. Here we demonstrated that Fe(2+) enhanced an uptake of exogenous Abeta 1
      40 and its deposition together with APOE in lysosomes in myocytes. Abeta deposits
      were associated with lipid-peroxidation and protein ubiquitination, and were more
      abundant and stable in epsilon4/epsilon4 than in epsilon3/epsilon3 cells. In
      organotypic cultures of brain vessels Fe(2+) induced deposition of non-fibrillar
      and fibrillar Abeta 1-40 in vascular tunica media. We hypothesize that locally
      increased concentrations of iron induce accumulation of exogenous and endogenous
      Abeta in SMCs, triggering beta-amyloid angiopathy. The greater susceptibility of
      epsilon4 carriers to Fe(2+) ions may result in an increased risk of beta
      amyloidosis.

PMID- 15993988
TI  - [Churg-Strauss syndrome relapse when antileucotriene in taggered].

PMID- 15993989
TI  - SARS coronavirus spike polypeptide DNA vaccine priming with recombinant spike
      polypeptide from Escherichia coli as booster induces high titer of neutralizing
      antibody against SARS coronavirus.
AB  - Different forms of SARS coronavirus (SARS-CoV) spike protein-based vaccines for
      generation of neutralizing antibody response against SARS-CoV were compared using
      a mouse model. High IgG levels were detected in mice immunized with
      intraperitoneal (i.p.) recombinant spike polypeptide generated by Escherichia
      coli (S-peptide), mice primed with intramuscular (i.m.) tPA-optimize800 DNA
      vaccine (tPA-S-DNA) and boosted with i.p. S-peptide, mice primed with i.m.
      CTLA4HingeSARS800 DNA vaccine (CTLA4-S-DNA) and boosted with i.p. S-peptide, mice
      primed with oral live-attenuated Salmonella typhimurium (Salmonella-S-DNA
      control) and boosted with i.p. S-peptide, mice primed with oral live-attenuated
      S. typhimurium that contained tPA-optimize800 DNA vaccine (Salmonella-tPA-S-DNA)
      and boosted with i.p. S-peptide, and mice primed with oral live-attenuated S.
      typhimurium that contained CTLA4HingeSARS800 DNA vaccine (Salmonella-tPA-S-DNA)
      and boosted with i.p. S-peptide. No statistical significant difference was
      observed among the Th1/Th2 index among these six groups of mice with high IgG
      levels. Sera of all six mice immunized with i.p. S-peptide, i.m. DNA vaccine
      control and oral Salmonella-S-DNA-control showed no neutralizing antibody against
      SARS-CoV. Sera of the mice immunized with i.m. tPA-S-DNA, i.m. CTLA4-S-DNA, oral
      Salmonella-S-DNA-control boosted with i.p. S-peptide, oral Salmonella-tPA-S-DNA,
      oral Salmonella-tPA-S-DNA boosted with i.p S-peptide, oral Salmonella-CTLA4-S-DNA
      and oral Salmonella-CTLA4-S-DNA boosted with i.p. S-peptide showed neutralizing
      antibody titers of <1:20-1:160. Sera of all the mice immunized with i.m. tPA-S
      DNA boosted with i.p. S-peptide and i.m. CTLA4-S-DNA boosted with i.p. S-peptide
      showed neutralizing antibody titers of >or=1:1280. The present observation may
      have major practical value, such as immunization of civet cats, since production
      of recombinant proteins from E. coli is far less expensive than production of
      recombinant proteins using eukaryotic systems.

PMID- 15993990
TI  - Well-defined and potent liposomal meningococcal B vaccines adjuvated with LPS
      derivatives.
AB  - Potent liposomal PorA formulations containing various lipopolysaccharide (LPS)
      derivatives were developed. The following adjuvants were compared: the commonly
      used aluminum phosphate (AlPO(4)), and three LPS like adjuvants: monophosphoryl
      lipid A (MPL), lipopolysaccharide (galE LPS) and the less toxic LPS mutant lpxL1.
      The immunogenicity in mice was evaluated and compared with that against an outer
      membrane vesicle (OMV) vaccine. The IgG isotype distribution and bactericidal
      activity were determined. Furthermore, PorA specific proliferation of lymph node
      cells after immunization and restimulation in vitro was studied with selected
      formulations. Both AlPO(4) and MPL were unable to improve the functional
      immunogenicity (i.e. bactericidal response) of liposomal PorA. Besides, when
      these adjuvants were used, the percentage of responders in the groups did not
      reach 100%. This was also observed with non adjuvated PorA-liposomes or OMV. Of
      the adjuvants studied, only galE LPS and lpxL1 LPS were capable of increasing the
      immunogenicity and avoid non responsiveness against PorA-liposomes. Importantly,
      the adjuvant activity of lpxL1 LPS was accompanied by an improved PorA specific
      proliferation of lymph node cells and a concomitant increase in IL-2 production.
      In conclusion and considering its lower toxicity, lpxL1 LPS adjuvated liposomes
      are superior to other formulations tested.

PMID- 15993991
TI  - Microcomputed tomography used in the analysis of the morphology of root canals in
      extracted wisdom teeth.
AB  - Microcomputed tomography is a new technique for the non-destructive study of
      porous biological materials. We examined 11 wisdom teeth that had been removed
      prophylactically by microcomputed tomography operating in the cone beam mode. The
      two-dimensional sections of the teeth were reconstructed with surface rendering
      software to provide three-dimensional models that were observed and handled in
      virtual reality. The tooth itself, or the pulp chamber and canals, can be
      reconstructed and observed separately or simultaneously. Many teeth looked
      dystrophic with abnormal distributions of roots and canals. Microcomputed
      tomography seems to be a promising way of studying dental anatomy.

PMID- 15993992
TI  - The origins of the thenar and hypothenar muscles.
AB  - This paper presents an anatomical study of the origins of the thenar and
      hypothenar muscles and postulates the causes of weakness and pillar pain
      following carpal tunnel release.

PMID- 15993993
TI  - Non-infective subcutaneous emphysema of the hand secondary to a minor webspace
      injury.
AB  - Subcutaneous emphysema in the hand is commonly associated with infection or high
      pressure injection injuries, with other non-infectious causes being reported as
      rarities in the literature. We describe an unusual case of minor injury to the
      first webspace resulting in significant subcutaneous emphysema.

PMID- 15993994
TI  - The impact of pumped water from a de-watered Magnesian limestone quarry on an
      adjacent wetland: Thrislington, County Durham, UK.
AB  - Although quarrying is often cited as a potential threat to wetland systems, there
      is a lack of relevant, quantitative case studies in the literature. The impact of
      pumped groundwater discharged from a quarry into a wetland area was assessed
      relative to reference conditions in an adjacent fen wetland that receives only
      natural runoff. Analysis of vegetation patterns at the quarry wetland site, using
      Detrended Correspondence Analysis and the species indicator values of Ellenberg,
      revealed a clear disparity between community transitions in the quarry wetland
      and the reference site. Limited establishment of moisture-sensitive taxa, the
      preferential proliferation of robust wetland species and an overall shift towards
      lower species diversity in the quarry wetland were explicable primarily by the
      physico-chemical environment created by quarry dewatering. This encompassed high
      pH (up to 12.8), sediment-rich effluent creating a nutrient-poor substrate with
      poor moisture retention in the quarry wetland, and large fluctuations in water
      levels.

PMID- 15993995
TI  - Evidence for potential impacts of ozone on Pinus cembra L. at mountain sites in
      Europe: an overview.
AB  - We summarize what is known about the impact of ozone (O(3)) on Pinus cembra in
      the timberline ecotone of the central European Alps and the Carpathian Mountains.
      In the central European Alps exposure to ambient and two-fold ambient O(3)
      throughout one growing season did neither cause any visible injury nor affect the
      photosynthetic machinery and biochemical parameters in current to 1-year-old
      needles. By contrast, in the southern French Alps and in the Carpathians 1-year
      old needles of Pinus cembra trees showed visual symptoms similar to those
      observed in O(3) stressed pine stands in southern California. For the southern
      French Alps the observed symptoms could clearly be attributed O(3) and
      differences in O(3) uptake seems to be the likely key factor for explaining the
      observed decline. For the Carpathians however, other reasons such as drought may
      not be excluded in eliciting the observed symptoms. Thus, the action of O(3) has
      always to be evaluated in concert with other environmental impacts, determining
      the tree's sensitivity to stress.

PMID- 15993996
TI  - Perchlorate in fish from a contaminated site in east-central Texas.
AB  - Perchlorate, a known thyroid endocrine disruptor, contaminates surface waters
      near military instillations where solid fuel rocket motors are manufactured or
      assembled. To assess potential perchlorate exposure to fish and the human
      population which may feed on them, fish were collected around the Naval Weapons
      Industrial Reserve Plant in McLennan County, TX, and analyzed for the presence of
      the perchlorate anion. The sampling sites included Lake Waco and Belton Lake, and
      several streams and rivers within their watersheds. The general tendency was that
      perchlorate was only found in a few species sampled, and perchlorate was not
      detected in every individual within these species. When detected in the fish,
      perchlorate tissue concentrations were greater than that in the water. This may
      be due to highly variable perchlorate concentrations in the water coupled with
      individual-level variation in elimination from the body, or to routes of exposure
      other than water.

PMID- 15993997
TI  - Culture free DGGE and cloning based monitoring of changes in bacterial
      communities of salad due to processing.
AB  - To assess the possibilities of a culture-independent monitoring of bacterial
      communities in the food chain, samples of salad from farming sites as well as
      corresponding, processed products in stores were analysed. The bacterial DNA was
      extracted using a modified soil extraction protocol. Amplification of 16S rDNA
      was carried out using primers specific for eubacteria and enterobacteriaceae.
      Fingerprints of 200/370 bp respectively were obtained by denaturing gradient gel
      electrophoresis (DGGE) analysis following PCR and nested PCR amplification. In
      parallel to DGGE analysis, clone libraries containing PCR fragments of the
      ribosomal gene were constructed and clones were screened by DGGE. DGGE analysis
      indicated a high diversity of bacterial communities in salad samples.
      Fingerprints indicated clearly reduced diversity of bacterial communities in
      processed samples from markets compared to field-grown salads. Surprisingly,
      primers pointed out in literature as specific for enterobacteriaceae did amplify
      pseudomonadeceae as well. Therefore, the more specific primers fD2 and rP1 were
      used subsequently in this study to amplify specific members of the family
      enterobacteriaceae. A total of 11 different 16S rDNA sequences were obtained and
      subjected to sequencing and phylogenetic affiliation. Sequences derived from the
      eubacterial clone library from organically farmed salad were affiliated to the
      family microbacteriaceae and pseudomonadaceae. In addition, a potential new genus
      within the family of enterobacteriaceae was detected. Furthermore, a sequence
      showing 98.9% similarity to Pseudomonas libaniensis (fluorescence subgroup) was
      found in a processed salad sample but not in the corresponding field samples.
      This species is generally known as an opportunistic pathogen. Whereas molecular
      based monitoring of bacterial communities in food still may need more experience
      and standardisation to detect specific bacteria present, the monitoring strategy
      presented in this paper, combining DGGE analysis with the construction of clone
      libraries, is an attractive method for culture-independent monitoring of changes
      of bacterial communities in the food chain.

PMID- 15993998
TI  - Garcinia cambogia toxicity is misleading.

PMID- 15993999
TI  - Measurement of radical-scavenging ability in hepatic metallothionein of rat using
      in vivo electron spin resonance spectroscopy.
AB  - In this study, the ability of metallothionein (MT) to scavenge free radicals was
      determined by in vivo electron spin resonance (ESR) spectroscopy using a
      carbamoyl-PROXYL, nitroxyl radical, as a spin probe. Production of
      metallothionein was induced in the liver of rats with ZnSO(4) (0.2 mol/kg, ip)
      and the intensity of the carbamoyl-PROXYL ESR signal was measured at the upper
      abdominal level which is a position of the liver. After the injection of
      carbamoyl-PROXYL, the peak of ESR signal gradually decreased and showed a linear
      decay curve. The rate of decay of carbamoyl-PROXYL, the spin clearance rate, was
      determined over the first 3 min. The spin clearance rate did not differ
      significantly between ZnSO(4)-treated and control rats. When rats were fasted for
      24 h, hepatic glutathione (GSH) concentrations decreased significantly and the
      spin clearance rate was significantly lower than non-fasted rats. However, the
      spin clearance rate of the fasted rats treated with Zn returned to the control
      level. To reduce GSH concentrations in the liver, buthionine sulfoximine (BSO, 2
      mmol/kg, ip) was injected into the rats. The spin clearance rate of rats treated
      with BSO was significantly decreased as compared with that of control rats
      without BSO treatment. In rats treated with Zn, the decay rate of carbamoyl
      PROXYL increased significantly in spite of the depletion of the hepatic GSH
      caused by BSO treatment, and returned to the control level. These results
      indicate that when the hepatic GSH concentration was significantly decreased by
      fasting and the administration of BSO, hepatic MT acted as a scavenger of free
      radicals. We suggest that GSH and MT act cooperatively as antioxidants to
      scavenge free radicals produced in response to various forms of stress, and MT
      serves as a second rather than the first line of defense.

PMID- 15994000
TI  - Use of metal conditioners to improve bond strengths of autopolymerizing denture
      base resin to cast Ti-6Al-7Nb and Co-Cr.
AB  - OBJECTIVE: The shear bond strengths of an autopolymerizing denture base resin to
      cast Ti-6Al-7Nb and Co-Cr alloys using three metal conditioners were
      investigated. METHODS: Ti-6Al-7Nb alloy and Co-Cr alloy discs were cast. The disc
      surfaces were air-abraded with 50 microm alumina particles and treated with three
      metal conditioners (Alloy Primer; Cesead II Opaque Primer; Metal Primer II). An
      autopolymerizing denture base resin was applied on the discs within a hole
      punched in a piece of sticky tape and a Teflon ring to define the bonding area.
      All specimens were immersed in 37 degrees C water for 24 h. Half of the specimens
      were thermocycled up to 20,000 cycles. The shear bond strengths were determined
      at a crosshead speed of 1.0 mm/min. RESULTS: Specimens treated with the three
      metal conditioners had significantly (p<0.05) improved shear bond strengths of
      the autopolymerizing denture base resin to both Ti-6Al-7Nb and Co-Cr. Although
      the bond strengths of the bonded Ti-6Al-7Nb specimens were higher than those of
      the Co-Cr alloy before thermocycling, the decrease in the bond strength of Ti-6Al
      7Nb was considerably greater than that of the Co-Cr after thermocycling.
      CONCLUSION: Significant improvements in bond strength of the autopolymerizing
      denture base resin to cast Ti-6Al-7Nb alloy and Co-Cr alloy were achieved through
      the application of Alloy Primer, Cesead II Opaque Primer and Metal Primer II. The
      bond durability to Ti-6Al-7Nb alloy was inferior to that to Co-Cr.

PMID- 15994001
TI  - Interaction of fluoxetine with phosphatidylcholine liposomes.
AB  - Fluoxetine (Prozac) is one of the latest of a new generation of antidepressants,
      approved by FDA in 2002. The interactions of fluoxetine with multilamellar
      liposomes of pure phosphatidylcholine (PC) or containing cholesterol 10% molar
      were studied as a function of the lipid chain lengths, using differential
      scanning calorimetry and spin labelling EPR techniques. The DSC profiles of the
      gel-to-fluid state transition of liposomes of DMPC (C14:0) are broadened and
      shifted towards lower temperatures at increasing dopant concentrations and, with
      less than 10% fluoxetine, any detectable transition is destroyed. The broadened
      profiles and the lowered transition temperatures demonstrate that both the size
      and the packing of the cooperative units undergoing the transition are modified
      by fluoxetine, leading to a looser and more flexible bilayer. No phase separation
      was observed. The effects of fluoxetine on the thermotropic phase behaviour of
      DPPC (C16:0) and, even more, of DSPC (C18:0) are different from that of DMPC. In
      fact, in the former cases, two peaks appeared at increasing dopant
      concentrations, suggesting the occurrence of a phase separation phenomenon, which
      is a sign of a binding of fluoxetine in the phosphate region. In cholesterol
      containing membranes, fluoxetine, even at low concentrations, leads to a general
      corruption of the membrane, both in terms of packing and cooperativity, and the
      formation of any new phase is no longer observable. EPR spectra reflect the
      disordered motion of acyl chains in the bilayer. It was found that fluoxetine
      lowers the order of the lipid chains mainly in correspondence of the fifth carbon
      position of SASL, indicating a possible accumulation near the interfacial region.

PMID- 15994002
TI  - Laparoscopic management of cryptorchidism in adults.
AB  - OBJECTIVES: Little is reported on the management of impalpable testis in adults.
      We present the impact of laparoscopy in this patient group. PATIENTS AND METHODS:
      Twelve adult patients have been referred to our centre over the last year, with
      impalpable testis. Pre-operative assessment was by either ultrasound or magnetic
      resonance imaging (MRI) or both. Quality of life and patient satisfaction were
      assessed by validated SF8 and client satisfaction (CSQ-8) questionnaires.
      Patients were also administered a self constructed questionnaire specifically
      looking at the impact of a laparoscopic service on their condition. RESULTS: The
      mean age was 29 yrs (range: 19-36). Two patients declined treatment. Of ten
      patients undergoing transperitoneal laparoscopy, five had intra-abdominal testes
      treated by laparoscopic orchidectomy (none malignant), two had the vas going into
      the deep ring and needed inguinal orchidectomy for an impalpable nubbin while in
      three cases there were blind ending vessels and vas. SF8 scores for physical
      HRQoL were unchanged but mental scores were significantly improved (p < 0.03).
      All patients were completely satisfied with a mean CSQ-8 score of 30.6 out of a
      possible 32. The majority of patients indicated that the availability of a
      laparoscopic service had prompted them to seek medical advice. CONCLUSIONS:
      Laparoscopic examination and orchidectomy is a safe and reliable procedure.
      Excellent patient satisfaction and quality of life are achievable. In particular
      mental health scores improve as previous uncertainty is removed. The advent of
      laparoscopy has encouraged adult patients to seek advice regarding a condition
      that has been present since childhood. We advocate the use of laparoscopy in
      evaluating and treating adult patients with maldescended testes.

PMID- 15994003
TI  - EAU guidelines on the diagnosis and treatment of urothelial carcinoma in situ.
AB  - OBJECTIVES: On behalf of the European Association of Urology (EAU), guidelines
      for the diagnosis, therapy and follow-up of patients with urothelial carcinoma in
      situ (CIS) have been established. METHOD: The recommendations in these guidelines
      are based on a recent comprehensive overview and meta-analysis in which two panel
      members have been involved (RS and AVDM). A systematic literature search was
      conducted using Medline, the US Physicians' Data Query (PDQ), the Cochrane
      Central Register of Controlled Trials, and reference lists in trial publications
      and review articles. RESULTS: Recommendations are provided for the diagnosis,
      conservative and radical surgical treatment, and follow-up of patients with CIS.
      Levels of evidence are influenced by the lack of large randomized trials in the
      treatment of CIS.

PMID- 15994004
TI  - Re: Daha LK, Riedl CR, Lazar D, Hohlbrugger G, Pfluger H. Do cystometric findings
      predict the results of intravesical hyaluronic acid in women with interstitial
      cystitis? Eur Urol 2005; 47: 393-7.

PMID- 15994005
TI  - Chemopreventive effect of bicyclol on malignant transformation of WB-F344 rat
      liver epithelial cells and its effect on related signal transduction in vitro.
AB  - The preventive effect of bicyclol, a novel anti-hepatitis drug, on
      hepatocarcinogenesis and its mechanism of action was studied in vitro. The
      results clearly indicated that bicyclol at non-toxic doses prevented the
      malignant transformation of WB-F344 cells (WB cells) induced by 3
      methylcholanthrene (3MC) and 12-O-tetradecanoyl phorbol 13-acetate (TPA).
      Furthermore, bicyclol inhibited proliferation of quiescent WB cells stimulated by
      TPA and blocked TPA-induced down-regulation of the gap junctional intercellular
      communication (GJIC). Immunoblot analysis demonstrated that bicyclol exhibited a
      remarkable reversing effect on TPA-induced cPKC-alpha and phosphor-ERK1/2
      expressions. In addition, bicyclol attenuated TPA-induced IkappaB-alpha
      degradation. In conclusion, our results support that bicyclol has chemopreventive
      action against hepatocarcinogenesis through inhibition of related signal
      transduction.

PMID- 15994006
TI  - Evaluation of electrokinetic removal of heavy metals from sewage sludge.
AB  - The presence of heavy metals is one of the main obstacles for agricultural use of
      million tonnes of dewatered sewage sludge produced in wastewater treatment
      plants. Electrokinetic (EK) treatment can be applied to remove heavy metals from
      sludge. The aim of this study was to increase the efficiency of electrokinetic
      removal of heavy metals from dewatered sewage sludge. EK experiments were carried
      out with and without pH adjustment in cathode chamber of acidified sewage sludge.
      The selective sequential extraction (SSE) was used to determine the fractionation
      of heavy metals in sewage sludge. The mobility of heavy metals in sludge
      significantly increased after its acidification at pH 2.7 and followed the order:
      Ni, Zn, Cu, As, Cr, Pb. Removal efficiencies of heavy metals in the experiment
      with acidified sewage sludge and pH adjustment at cathode chamber at 2.0 were:
      95% for Zn, 96% for Cu, 90% for Ni, 68% for Cr, 31% for As and 19% for Pb. The
      concentrations of Zn, Cu, Ni, Cr and Pb after EK treatment were below the United
      States Environmental Protection Agency limits for biosolids applied to
      agricultural land, forest, public contact sites or reclamation sites.

PMID- 15994007
TI  - Doramectin concentration profiles in the gastrointestinal tract of topically
      treated calves: Influence of animal licking restriction.
AB  - Endectocide compounds are extensively used for broad-spectrum parasite control
      and their topical administration to cattle is widespread in clinical practice.
      Pour-on formulations of moxidectin, ivermectin, eprinomectin and doramectin (DRM)
      are marketed internationally for use in cattle. However, variability in
      antiparasitic efficacy and pharmacokinetic profiles has been observed. Although
      the tissue distribution pattern for different endectocide molecules given
      subcutaneously to cattle has been described, only limited information on drug
      concentration profiles in tissues of parasite location after topical treatment is
      available. Understanding the plasma and target tissue kinetics for topically
      administered endectocide compounds is relevant to optimise their therapeutic
      potential. The current work was designed to measure the plasma and
      gastrointestinal (GI) concentration profiles of DRM following its pour-on
      administration to calves. The influence of natural licking behaviour of cattle on
      DRM concentration in mucosal tissue and luminal content of different GI sections
      was evaluated. The trial was conducted in two experimental phases. In Phase I,
      the DRM plasma kinetics was comparatively characterised in free-licking and in 2
      day licking-restricted (non-licking) calves. The pattern of distribution of
      topical DRM to mucosal and luminal contents from abomasum, duodenum, ileum,
      caecum and spiral colon was assessed in free-licking and non-licking calves
      restricted over 10 days post-administration (Phase II). The prevention of licking
      caused marked changes on the plasma and GI kinetics of DRM administered pour-on.
      In 2-day licking restricted calves, DRM systemic availability was significantly
      lower (29%) than in free licking animals during the first 9 days post-treatment.
      Following a 10-day long licking restriction period, DRM concentrations profiles
      in both mucosal tissue and luminal contents of the GI tract were markedly higher
      in animals allowed to lick freely. This enhancement in drug concentrations in
      free-licking compared to non-licking calves, was particularly pronounced in the
      abomasal (38-fold higher) and duodenal (six-fold higher) luminal content. As
      shown earlier for ivermectin, licking behaviour may facilitate the oral ingestion
      of topically-administered DRM in cattle. This would be consistent with the marked
      lower drug concentration profiles measured in the bloodstream and GI tract of the
      animals prevented from licking. The work reported here provides relevant
      information on the pattern of DRM distribution to the GI tract after pour-on
      treatment, and contributes to understand the variability observed in the
      antiparasitic persistence of topically-administered endectocides in cattle. The
      implications of natural licking in topical treatments are required to be
      seriously assessed to achieve optimal parasite control and to design
      parasitological and pharmacological studies within the drug approval process.

PMID- 15994008
TI  - Two-dimensional electrophoresis and mass spectrometry for the identification of
      species-specific Trichinella antigens.
AB  - A proteomic approach was utilized for fine antigenic characterization of the
      closely related Trichinella genotypes Trichinella britovi T3 and Trichinella T8.
      Crude extract of muscle larvae L1 (LCE) from both isolates were analyzed by 2D
      PAGE. Over 500 protein spots were reproducibly separated in both genotypes. These
      separated proteins were identified in Western blot with IgG1 and IgG3 from
      homologous and heterologous hyperimmune sera raised in BALB/c mice. A group of 20
      and 15 spots migrating at 50--60 k Da and pH 5.5--6.5 in T. britovi and
      Trichinella T8 maps, respectively, reacted with the IgG1 from heterologous sera
      whereas a group of minor spots of similar migration patterns did not. Low cross
      reactivity occurred for IgG3. MALDI-TOF and MALDI-TOF/TOF analysis of these
      antigens identified a predicted enolase, the protein P 49 and a predicted actin
      among the cross-reactive proteins and two hypothetical actins among the non cross
      reactive proteins.

PMID- 15994009
TI  - Viability and infectiousness of eggs of Echinococcus granulosus aged under
      natural conditions of inferior arid climate.
AB  - We studied the viability and infectiousness of aged Echinococcus granulosus eggs
      by in vivo evaluation in ovines. Our results demonstrated that after 41 months of
      ageing of the eggs under environmental conditions of an inferior arid climate
      (Patagonia, Argentina), they were still able to produce infection in 4/4 ovines
      challenged with 1200 eggs per ovine. In the ovines experimentally infected with
      these aged eggs, the occurrence of hepatic and pulmonary cysts was determined by
      necropsy, histologic and genetic studies. The eggs were found in a semi-senescent
      stage, thus keeping their capacity to generate an infection in the intermediary
      ovine host.

PMID- 15994010
TI  - The prevalence of Trichinella infection in domestic dogs in Finland.
AB  - In this study, we examined the prevalence of Trichinella infection in domestic
      dogs in Finland, which is known to have a high prevalence of Trichinella
      infection in sylvatic hosts. Altogether 727 dog serum samples were tested
      serologically by ELISA with ES-antigen in dilutions 1:50, 1:100, 1:200, and
      1:400. Additionally, muscle samples from 102 dogs' front leg extensors were
      tested parasitologically by HCl-pepsin-digestion. The tested dogs originated from
      the University Veterinary Hospital (244 of the sera and all of the
      parasitologically tested muscle samples) and from a serum bank of the National
      Veterinary and Food Research Institute (465 serum samples), representing healthy
      dogs mostly from southern Finland. As negative controls, we tested sera from 18
      experimental dogs known to be negative for Trichinella infection. Trichinella
      spp. was isolated from one dog (1%) with a low infection intensity. High OD% were
      found in both groups of serum samples. Of the hospitalized dogs, 4.9% were
      classified positive, and 8.6% of the healthy dogs were classified positive (7.3%
      in total). The sex or breed of the tested dogs did not correlate with the
      positive results, but the age correlated positively in the serum bank group. The
      serological results suggest that dogs may be exposed to Trichinella spp. in
      Finland; however, confirmation of low-level infections requires confirmation by
      direct testing methods.

PMID- 15994011
TI  - Comparison of trichinelloscopy with a digestion method for the detection of
      Trichinella larvae in muscle tissue from naturally infected pigs with low level
      infections.
AB  - The identification of Trichinella infection in pigs in Croatia has traditionally
      been done by inspection of individual carcasses. In response to outbreaks of
      human trichinellosis in the last decade, the Croatian Ministry of Agriculture and
      Forestry instituted compulsory trichinelloscopic examination of tissue from both
      commercially and privately slaughtered swine. The purpose of this study was to
      compare trichinelloscopy and artificial digestion for use in samples containing
      low numbers of larvae. Each assay was used to test 1,769 field positive samples,
      290 of which contained 6 or less larvae per gram of muscle tissue. The
      sensitivity and specificity of trichinelloscopy with 6 or less l pg was 43.4 and
      88%, respectively. kappa-Value as a measure of agreement between trichinelloscopy
      and artificial digestion was 0.27%. It is noteworthy that a considerable number
      of the 103 (52%) negative animals on trichinelloscopy contained>or=6l pg which is
      enough to cause clinical trichinellosis. These findings support other studies
      that indicate trichinelloscopy is not a method of choice and that it is necessary
      to implement more sensitive procedures such as artificial digestion.

PMID- 15994012
TI  - Negative and positive regulation of HIF-1: a complex network.
AB  - Hypoxia inducible factor-1 (HIF-1) is as a key transcriptional mediator of the
      hypoxic response in eukaryotic cells, regulating the expression of a myriad of
      genes involved in oxygen transport, glucose uptake and glycolysis and
      angiogenesis. Deregulation of HIF-1 activity occurs in many human cancers,
      usually at the level of the HIF-1alpha subunit. HIF-1 is regulated by a variety
      of mechanisms including transcription, translation post-translational
      modification, protein-protein interaction and degradation. Our understanding of
      the key signalling pathways that regulate HIF-1 has significantly progressed in
      recent years and has highlighted the potential for targeting the HIF-1 pathway as
      a basis for the development of new cancer therapies.

PMID- 15994013
TI  - Lubricant and razor debridement in partial thickness burn.
AB  - By aiming to relieve pain from removing blisters in partial thickness burn, we
      tested whether the application of a sterile lubricant (KY-Jelly) on blisters and
      the use of a sterile razor to remove their roof can reduce algesia in humans,
      compared to a conventional method. A prospective randomized controlled designed
      study was performed on 20 patients. A visual pain scale was used by patients to
      evaluate pain experienced.

PMID- 15994014
TI  - The assessment of erythema and thickness on burn related scars during pressure
      garment therapy as a preventive measure for hypertrophic scarring.
AB  - The aim of this study was threefold: (1) Assess the pressure loss of two types of
      pressure garments that are used in the treatment of hypertrophic scars after burn
      injury, (2) investigate the influence of two different levels of compression on
      erythema and thickness of burn scars and (3) examine the association between
      erythema and thickness. The study was a prospective trial in which 76 burn scars
      in 60 patients were objectively assessed with the Minolta Chromameter CR-300 for
      erythema and with the Dermascan C for thickness of the scar over a period of 3
      months. Each patient was randomly assigned to a "normal" or "lower" compression
      class treatment, with respectively mean values of 15 and 10 mmHg pressure after
      wearing the garment for 1 month. Measurements for both parameters were taken at
      0, 1, 2 and 3 months of treatment. Pressure garments with "normal" compression
      did lose significantly more compression over 1 month (4.82 mmHg) than did the
      garments from the low compression class (2.57 mmHg). Scars that were treated with
      garments from a "normal" compression class did score significantly better for
      thickness compared to the "low" compression class. The difference in thickness
      was most evident at 1 month. Thereafter no further significant improvement
      between the two different treatments over time could be obtained. This difference
      was not found for erythema. Positive correlations could be found between erythema
      and thickness values at all of the three test points while changes in erythema
      and thickness only correlated significantly after the first month. The pattern of
      change of both parameters correlated at a high level of significance after 3
      months of treatment. These data suggest that pressure garments that deliver a
      pressure of at least 15 mmHg pressure tend to accelerate scar maturation and that
      measurements of the pattern of change of the erythema can be used to predict
      changes in scar thickness and vice versa.

PMID- 15994015
TI  - Treatment of severe foot burns in children.
AB  - Only a few papers on the problem of foot burns can be found in the easily
      accessible scientific literature. In Central Asia foot burns are widespread,
      because many people, especially children, walk barefoot in summer, and because
      the heated sandal is still used for keeping warm in winter. In the Samarkand
      Inter-Regional Burn Center in Uzbekistan, the following method of treatment was
      developed: initial surgical debridement of the wound, necrectomy with application
      of chemotherapeutic medications and early necrectomy, the removal of necrotic
      tissues and preparation the wound for early autodermoplasty. This effective
      treatment method contributed to the restoration of foot function in patients,
      lessened their joint deformities and post-burn contractures/deformities, and also
      shortened their hospital stay.

PMID- 15994016
TI  - Major cytogenetic aberrations and typical multidrug resistance phenotype of uveal
      melanoma: current views and new therapeutic prospects.
AB  - Uveal melanoma is the most frequent intra-ocular cancer. The recent development
      of new chromosome-related technologies have permitted the elucidation of both the
      cytogenetics and the natural history of this disease. Fifty to 60% of uveal
      melanomas are linked to a monosomy 3, which appears as an early and determinant
      event in tumor progression. Tumors with this anomaly have a very poor prognosis.
      Recent work suggests that this category of uveal melanoma represents a distinct
      pathologic entity from that associated with normal disomy 3. Chromosome 6
      aberrations probably constitute a second entry point into the process of
      cancerogenesis, while gains in 8q seem to appear later in the natural history of
      uveal melanomas due to their higher frequency in larger tumors. Other anomalies
      will be reviewed. In spite of significant improvements in the local treatment of
      uveal melanoma, many patients die due to tumor metastasis. This disease is
      characterized by a constitutive chemoresistance whose typical multidrug
      resistance phenotype (MDR) is particularly complex since different combinations
      of several resistance proteins are simultaneously produced. Regulation of the
      expression of these proteins is a research priority, increasingly so as gene
      therapy-dependent chemosensitization strategies expand. Therefore, the
      development and improvement of methods to determine the chemoresistance profile
      become a crucial objective today in the therapeutic strategies against uveal
      melanoma.

PMID- 15994017
TI  - Odor response properties of neighboring mitral/tufted cells in the rat olfactory
      bulb.
AB  - Olfactory perception initiates in the nasal epithelium wherefrom olfactory
      receptor neurons--expressing the same receptor protein--project and converge in
      two different glomeruli within each olfactory bulb. Recent evidence suggests that
      glomeruli are isolated functional units, arranged in a chemotopic manner in the
      olfactory bulb. Exposure to odorants leads to the activation of specific
      populations of glomeruli. In rodents, about 25-50 mitral/tufted cells project
      their primary dendrites to a single glomerulus receiving similar sensory input.
      Yet, little is known about the properties of neighboring mitral/tufted cells
      connected to one or a few neighboring glomeruli. We used tetrodes to
      simultaneously record multiple single-unit activity in the mitral cell layer of
      anesthetized, freely breathing rats while exposed to mixtures of chemically
      related compounds. First, we characterized the odorant-induced modifications in
      firing rate of neighboring mitral/tufted cells and found that they do not share
      odorant response profiles. Individual units showed a long silent (11.01 ms)
      period with no oscillatory activity. Cross-correlation analysis between
      neighboring mitral/tufted cells revealed negligible synchronous activity among
      them. Finally, we show that respiratory-related temporal patterns are dissimilar
      among neighboring mitral/tufted cells and also that odorant stimulation results
      in an individual modification that is not necessarily shared by neighboring
      mitral/tufted cells. These results show that neighboring mitral/tufted cells
      frequently exhibit dissimilar response properties, which are not consistent with
      a precise chemotopic map at the mitral/tufted cell layer in the olfactory bulb.

PMID- 15994018
TI  - Early and transient increase in spontaneous synaptic inputs to the rat facial
      motoneurons after axotomy in isolated brainstem slices of rats.
AB  - Section of motor nerve fibers (axotomy) elicits a variety of morphofunctional
      responses in the motoneurons in the motor nuclei. Later than the fifth post
      operational day after section of the facial nerve, synapse elimination occurs in
      the facial motoneuron pool, leading to gradual abolishment of synaptic input
      driven activities of the axotomized motoneurons. However, it remains unknown how
      the amount of synaptic input changes during this period between the axotomy and
      the synaptic elimination. Here we examined a hypothesis that axotomy of the
      motoneurons itself modifies the synaptic inputs to the motoneurons. One day after
      axotomy, the postsynaptic currents, mostly mediated by non-N-methyl-D-aspartic
      acid (non-NMDA) receptors, recorded from the axotomized facial motoneurons in the
      acute slice preparations of the rats were of higher frequency and larger
      amplitude than those in the intact motoneurons. This difference was not observed
      after the third post-operational day and appeared earlier than the changes in the
      electrophysiological properties and increase in the number of dead neurons in the
      axotomized motor nucleus. The larger postsynaptic current frequency of the
      axotomized motoneurons was observed both in the absence and in the presence of
      tetrodotoxin citrate, suggesting that increased excitability and facilitated
      release underlie the postsynaptic current frequency increase. These results
      suggest that synaptic re-organization occurs in the synapses of motoneurons at an
      early stage following axotomy.

PMID- 15994019
TI  - Sex differences in expression of transforming growth factor-alpha and epidermal
      growth factor receptor mRNA in Waved-1 and C57Bl6 mice.
AB  - A reduction of transforming growth factor-alpha (TGFalpha) expression in the
      spontaneous Waved-1 (Wa-1) mutant mouse causes specific behavioral and anatomical
      changes, including reduced fear learning and stress response and enlarged lateral
      ventricles. These alterations are observed predominantly in male Wa-1 mice after
      puberty. We hypothesized that regional differences in the expression of TGFalpha
      and its receptor, epidermal growth factor receptor (EGFR), may regulate the
      sexual dimorphism of the brain structures and functions during postnatal
      development. In general, fear learning-associated structures, including
      hippocampus and amygdala, showed maximum expression before puberty, regardless of
      genotype. In contrast, an overall temporal delay in the rise of both transcript
      levels, which peaked around or after puberty onset, was observed for the major
      stress regulatory hypothalamo-pituitary-adrenal axis. This pattern of expression
      was reversed for amygdala EGFR and hypothalamus TGFalpha and EGFR transcripts in
      males. When regional TGFalpha expression was compared between control and Wa-1
      mice, far more complex patterns than expected were observed that revealed sex-
      and structure-dependent differences. In fact, the amygdala, hypothalamus, and
      pituitary TGFalpha expression pattern in Wa-1 exhibited a clear sex dependency
      across various age groups. Surprisingly, there was no compensatory up-regulation
      of the EGFR transcript in Wa-1 mice. The observed expression patterns of the
      TGFalpha signaling system during normal development and in the Wa-1 mutant mouse
      suggest complex sex- and age-dependent transcription regulatory mechanisms.

PMID- 15994020
TI  - Unusual astrocyte reactivity caused by the food mycotoxin ochratoxin A in
      aggregating rat brain cell cultures.
AB  - Ochratoxin A (OTA), a mycotoxin and widespread food contaminant, is known for its
      patent nephrotoxicity and potential neurotoxicity. Previous observations in vitro
      showed that in the CNS, glial cells were particularly sensitive to OTA. In the
      search for the molecular mechanisms underlying OTA neurotoxicity, we investigated
      the relationship between OTA toxicity and glial reactivity, in serum-free
      aggregating brain cell cultures. Using quantitative reverse transcriptase
      polymerase chain reaction to analyze changes in gene expression, we found that in
      astrocytes, non cytotoxic concentrations of OTA down-regulated glial fibrillary
      acidic protein, while it up-regulated vimentin and the peroxisome proliferator
      activated receptor-gamma expression. OTA also up-regulated the inducible nitric
      oxide synthase and the heme oxygenase-1. These OTA-induced alterations in gene
      expression were more pronounced in cultures at an advanced stage of maturation.
      The natural peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy
      delta(12,14) prostaglandin J2, and the cyclic AMP analog, bromo cyclic AMP,
      significantly attenuated the strong induction of peroxisome proliferator
      activated receptor-gamma and inducible nitric oxide synthase, while they
      partially reversed the inhibitory effect of OTA on glial fibrillary acidic
      protein. The present results show that OTA affects the cytoskeletal integrity of
      astrocytes as well as the expression of genes pertaining to the brain
      inflammatory response system, and suggest that a relationship exists between the
      inflammatory events and the cytoskeletal changes induced by OTA. Furthermore,
      these results suggest that, by inducing an atypical glial reactivity, OTA may
      severely affect the neuroprotective capacity of glial cells.

PMID- 15994022
TI  - Hypothalamic and zona incerta neurons expressing hypocretin, but not melanin
      concentrating hormone, project to the hamster intergeniculate leaflet.
AB  - The hypocretins (Hcrt; also known as orexins) and melanin-concentrating hormone
      comprise distinct families of neuropeptides synthesized in cells located in the
      lateral hypothalamus and adjacent areas. The Hcrts are thought to modulate food
      intake and sleep/wake patterns in mammals. Melanin-concentrating hormone has a
      well-documented role in energy metabolism. A moderate plexus of Hcrt
      immunoreactive terminals has been described in the hamster intergeniculate
      leaflet, part of the circadian rhythm system. This study investigated the origin
      of Hcrt-immunoreactive terminals in the intergeniculate leaflet and determined
      whether melanin-concentrating hormone neurons also project to the intergeniculate
      leaflet. The tracer, cholera toxin beta-subunit, was injected into the
      intergeniculate leaflet of the golden hamster. Double-label fluorescent
      immunohistochemistry for cholera toxin beta-subunit and Hcrt or melanin
      concentrating hormone was then performed to identify retrogradely labeled cells
      also containing immunoreactive peptide. Most cholera toxin beta-subunit-labeled
      cells were detected in the medial zona incerta and sub-incertal zone, with few
      observed in the lateral hypothalamus. Hcrt-immunoreactive cells were abundant and
      found largely in the lateral hypothalamus and adjacent nuclei. Melanin
      concentrating hormone cells were also abundant in the medial zona incerta, in
      close proximity to cholera toxin beta-subunit-labeled cells, but ventral to them.
      Cells containing both cholera toxin beta-subunit and Hcrt-immunoreactive, were
      present in the dorsal aspect of the lateral hypothalamus. The number observed was
      small, < or = 1% of the total number of Hcrt cells counted in the hamster. No
      cholera toxin beta-subunit-immunoreactive cells also contained melanin
      concentrating hormone and no melanin-concentrating hormone-immunoreactive
      processes were evident in the intergeniculate leaflet. The results show that a
      small number of lateral hypothalamus cells containing Hcrt-immunoreactivity
      project to the intergeniculate leaflet, but they are scattered rather than
      collected into a discrete group. At the present time there is no information
      regarding the function of these cells, although they may contribute to the
      regulation of sleep/arousal, circadian rhythmicity, or vestibulo-oculomotor
      function.

PMID- 15994023
TI  - Increased phospho-adducin immunoreactivity in a murine model of amyotrophic
      lateral sclerosis.
AB  - Adducins alpha, beta and gamma are proteins that link spectrin and actin in the
      regulation of cytoskeletal architecture and are substrates for protein kinase C
      and other signaling molecules. Previous studies have shown that expressions of
      phosphorylated adducin (phospho-adducin) and protein kinase C are increased in
      spinal cord tissue from patients who died with amyotrophic lateral sclerosis, a
      neurodegenerative disorder of motoneurons and other cells. However, the
      distribution of phospho-adducin immunoreactivity has not been described in the
      mammalian spinal cord. We have evaluated the distribution of immunoreactivity to
      serine/threonine-dependent phospho-adducin at a region corresponding to the
      myristoylated alanine-rich C kinase substrate-related domain of adducin in spinal
      cords of mice over-expressing mutant human superoxide dismutase, an animal model
      of amyotrophic lateral sclerosis, and in control littermates. We find phospho
      adducin immunoreactivity in control spinal cord in ependymal cells surrounding
      the central canal, neurons and astrocytes. Phospho-adducin immunoreactivity is
      localized to the cell bodies, dendrites and axons of some motoneurons, as well as
      to astrocytes in the gray and white matter. Spinal cords of mutant human
      superoxide dismutase mice having motoneuron loss exhibit significantly increased
      phospho-adducin immunoreactivity in ventral and dorsal horn spinal cord regions,
      but not in ependyma surrounding the central canal, compared with control animals.
      Increased phospho-adducin immunoreactivity localizes predominantly to astrocytes
      and likely increases as a consequence of the astrogliosis that occurs in the
      mutant human superoxide dismutase mouse with disease progression. These findings
      demonstrate increased immunoreactivity against phosphorylated adducin at the
      myristoylated alanine-rich C kinase substrate domain in a murine model of
      amyotrophic lateral sclerosis. As adducin is a substrate for protein kinase C at
      the myristoylated alanine-rich C kinase substrate domain, the increased phospho
      adducin immunoreactivity is likely a consequence of protein kinase C activation
      in neurons and astrocytes of the spinal cord and evidence for aberrant
      phosphorylation events in mutant human superoxide dismutase mice that may affect
      neuron survival.

PMID- 15994021
TI  - Central autonomic control of the bone marrow: multisynaptic tract tracing by
      recombinant pseudorabies virus.
AB  - Bone marrow is the primary place of hematopoiesis, where the development,
      survival and release of multipotent stem cells, progenitors, precursors and
      mature cells are under continuous humoral and neural control. Dense network of
      nerve fibers, containing various neurotransmitters is found in the bone marrow,
      however, the central neuronal circuit that regulates the activities of the bone
      marrow through these fibers remained unexplored. Transsynaptically connected
      neurons were mapped by virus-based transneuronal tracing technique using two
      isogenic, genetically engineered pseudorabies viruses, Bartha-DupGreen and Ba
      DupLac expressing green fluorescent protein and beta-galactosidase, respectively.
      Bartha-DupGreen was injected into the femoral bone marrow of male rats and the
      progression of infection was followed 4-7 days post-inoculation. Virus-labeled
      cells were revealed in ganglia of the paravertebral chain and in the
      intermediolateral cell column of the lower thoracic spinal cord. Neurons were
      retrogradely labeled in the C1, A5, A7 catecholaminergic cell groups and several
      other nuclei of the ventrolateral and ventromedial medulla, the periaqueductal
      gray matter, the paraventricular and other hypothalamic nuclei, and in the
      insular and piriform cortex. Nerve transections and double-virus tracing from the
      bone marrow and the surrounding muscles were used to confirm the specific
      spreading of the virus. These results provide anatomical evidence for the CNS
      control of the bone marrow and identify putative brain areas, which are involved
      in autonomic regulation of the hematopoiesis, the release of progenitor cells,
      the blood supply and the immune cell function in the bone marrow.

PMID- 15994024
TI  - Estrogen receptor alpha and beta mRNA expressions by proliferating and
      differentiating cells in the adult rat dentate gyrus and subventricular zone.
AB  - Numerous factors modulate neurogenesis in the adult dentate gyrus and
      subventricular zone, but it is often not clear if the modulation is mediated by
      direct effects on the proliferating and differentiating cells or secondary to
      effects on other cells. Also, while some factors selectively affect neurogenesis
      in one of the neurogenetic zones, it is not clear how selectivity is achieved.
      Estrogen is a hormonal modulator of neurogenesis. To address the issues of direct
      versus indirect control and regional specificity we investigated the
      colocalization of immunoreactivity for a proliferating cell marker, Ki-67, and a
      marker for migrating and differentiating cells with a neuronal phenotype,
      doublecortin, with the expressions of mRNA for estrogen receptors alpha and beta.
      We found an extensive colocalization of estrogen receptor alpha with both markers
      in the dentate gyrus and only with Ki-67 in the subventricular zone. An extensive
      colocalization of estrogen receptor beta with both markers was found in the
      dentate gyrus, but only a few Ki-67-immunoreactive and no doublecortin
      immunoreactive cells of the subventricular zone expressed estrogen receptor beta
      mRNA. Estrogen receptor alpha and beta mRNAs were not expressed in other
      telencephalic Ki-67-immunoreactive cells or in constitutively doublecortin
      immunoreactive cells of the piriform cortex. The extensive colocalization of
      immunoreactive markers for cell proliferation and differentiation with mRNAs for
      estrogen receptor alpha and estrogen receptor beta points to the direct
      modulation of dentate cell proliferation, differentiation and survival by
      estrogen, while direct effects of estrogen in the subventricular zone appear
      restricted to estrogen receptor alpha-mediated effects operating at the time of
      cell proliferation.

PMID- 15994025
TI  - Effect of fluoxetine and cocaine on the expression of clock genes in the mouse
      hippocampus and striatum.
AB  - Long-term drug-induced alterations in CNS gene expression may be responsible for
      some therapeutic effects, such as antidepressant action, as well as for
      psychopathological conditions, such as drug addiction and abuse. Transcription
      factors called "clock" genes can be affected by psychotropic drugs and may modify
      the expression pattern of other genes. In this study in mice, we investigated the
      delayed effects of single and repeated (i.e. 14 days) administration of the
      antidepressant fluoxetine and the psychostimulant cocaine on the brain expression
      of clock genes Period1, Period2, Period3, Clock, Bmal1, Cryptochrome1,
      Cryptochrome2, and NPAS2 (neuronal PAS domain protein 2), and their putative
      target gene, serotonin N-acetyltransferase. Mice were treated at ZT05 (lights on
      at 5:00 am; ZT00). Brain samples (i.e. hippocampus, striatum, and prefrontal
      cortex) were processed for a semi-quantitative mRNA assay. Repeated but not
      single treatment with either drug increased serotonin N-acetyltransferase
      expression in all areas tested. On the other hand, the expression of clock genes
      was differentially affected depending on the drug (i.e. fluoxetine and cocaine),
      treatment schedule (i.e. single and repeated), and brain area (i.e. hippocampus
      and striatum) tested. More pronounced changes were induced by repeated rather
      than single administrations of fluoxetine or cocaine. We propose that the effects
      of psychoactive drugs on clock transcription factors may mediate long-term drug
      induced changes, possibly by regulating the expression of a second set of genes
      (i.e. clock-controlled genes).

PMID- 15994026
TI  - Retirement and drinking outcomes: lingering effects of workplace stress?
AB  - This study assesses the degree to which sexual harassment (SH), generalized
      workplace abuse (GWA), and psychological workload (PWL) impact drinking behaviors
      in retirement. A mail survey was completed at four points in time by a cohort of
      1654 employees initially drawn from a university workplace. Questionnaires
      assessed experiences of SH, GWA, PWL and drinking behaviors. Hypotheses were
      tested involving (1) the extent to which SH, GWA, and PWL experienced while
      working were associated with frequency and quantity of drinking in retirement,
      (2) the extent to which drinking levels of retirees differed from those of
      current employees experiencing similar stress levels, and (3) the extent to which
      gender moderated these relationships. Retirees reporting earlier stressful work
      environments report higher levels of alcohol consumption during retirement
      compared to those retirees reporting less stressful earlier work environments.
      Gender moderated these relationships. The findings of this study suggest that
      there may be a residual effect of workplace stress during retirement.

PMID- 15994027
TI  - Comparison of normal tissue dose with three-dimensional conformal techniques for
      breast cancer irradiation including the internal mammary nodes.
AB  - PURPOSE: To compare the Para Mixed technique for irradiation of the internal
      mammary nodes (IMN) with three commonly used strategies, by analyzing the dose to
      the heart and other organs at risk. METHODS AND MATERIALS: Four different three
      dimensional conformal dose plans were created for 30 breast cancer patients. The
      IMN were enclosed with the Para Mixed technique by a widened mediolateral tangent
      photon beam and an anterior electron beam, with the Patched technique by an
      anterior electron beam, with the Standard technique by an anterior photon and
      electron beam, and with the PWT technique by partially wide tangents. All
      techniques were optimized for conformality and produced equally adequate target
      coverage. RESULTS: Heart dose was lowest with the Para Mixed and Patched
      technique for all patients and with the PWT technique for right-sided treatment
      only. Lung dose was highest with the PWT, lowest with the Patched, and
      intermediate with the Para Mixed and Standard techniques. Skin dose was highest
      with the Patched, lowest with the PWT, and intermediate with the Para Mixed and
      the Standard techniques. The Para Mixed technique resulted in a 13-Gy lower dose
      in an overlap area, and the PWT technique was the only technique that
      incorporated considerable volumes of the contralateral breast. CONCLUSION: The
      Para Mixed technique yielded the overall best results. No other technique
      resulted in a lower heart dose. Lung and skin were equally spared instead of one
      of them being compromised, and the contralateral breast was avoided.

PMID- 15994028
TI  - Addiction severity assessment tool: development of a self-report measure for
      clients in substance abuse treatment.
AB  - This article describes the development and reliability and validity testing of
      the Addiction Severity Assessment Tool (ASAT), a brief, 27-item multidimensional
      self-report measure of problem severity in daily functioning, relational
      functioning, dysphoric states, dependence severity, recovery skill/self-efficacy,
      and existential factors for adult substance abuse clients. Items generated for an
      Alpha version were conceptually and empirically evaluated. A Beta version
      underwent further empirical evaluation and item selection. Cross validation of
      the final version examined internal consistency, test-retest reliability, factor
      structure, and convergent/discriminant and known groups validity. Sensitivity to
      change was evaluated in a 3-month outcome study. Clients were recruited from
      inpatient, outpatient and residential substance abuse treatment centers, and a
      sample of 238 nonpatients were also recruited from community groups. The Beta
      version was tested with 201 clients, and cross validation involved 242 clients.
      Well-known standardized, self-report and interview-based comparison measures were
      used to test convergent/discriminant validity of the ASAT. Reliability
      coefficients for the six ASAT domains were acceptable. Reasonable
      convergent/discriminant and known groups, construct validity were demonstrated,
      along with sensitivity to change of the domain scale scores. The ASAT appears to
      comprise a useful new tool for assessing clinical outcomes of adult clients in
      substance abuse treatment.

PMID- 15994030
TI  - Evaluation of the discriminatory power of variable number tandem repeat (VNTR)
      typing of Mycobacterium bovis strains.
AB  - The discriminatory power of variable number tandem repeat (VNTR) typing based on
      16 known loci (12 MIRUs, 3 ETRs and VNTR 3232) was assessed for Mycobacterium
      bovis strains collected sequentially at the slaughterhouse of N'Djamena, Chad. Of
      67 M. bovis strains analyzed, 67% were clustered. In this study, VNTR typing was
      highly discriminative with an overall allelic diversity (h(oa)) of 0.922. We
      defined five loci (ETR A, B, C and MIRU 26, 27) as highly (h>0.25), two loci
      (MIRU 4, and VNTR 3232) as moderately (0.11<h<0.25) and three loci (MIRU 16, 20,
      31) as poorly (0.01<h<0.11) discriminative. Six loci (MIRU 2, 10, 23, 24, 39, and
      40) showed no polymorphism at all. VNTR typing of the five highly discriminative
      loci (h=0.917) proved to be most appropriate for first line typing of M. bovis
      strains of Chad and superior than spoligotyping (h(sp)=0.789). In contrast to
      Mycobacterium tuberculosis strains, a consensus on VNTR loci needs to be found
      for M. bovis strains. The selection of a generally agreed set of VNTR loci for
      molecular discrimination of M. bovis in different geographical settings is
      discussed.

PMID- 15994029
TI  - Heritable and inducible gene knockdown in C. elegans using Wormgate and the
      ORFeome.
AB  - Double-stranded RNA (dsRNA) mediated gene silencing (RNA interference; RNAi) is a
      powerful tool for investigating gene function. It is usually performed in
      Caenorhabditis elegans via the injection or oral delivery of dsRNA, but an
      alternative approach, the expression of RNA hairpins from introduced DNA (hairpin
      RNAi; hpRNAi) has several advantages: (1) it can be induced systemically or in a
      tissue-specific manner; (2) because it is heritable, it allows consistent RNAi
      silencing across a whole population of genetically identical animals; and (3) it
      can be applied in refractory tissue such as neurons. hpRNAi has not been widely
      used to investigate gene function because a number of steps are relatively
      inefficient and labour-intensive. We describe Wormgate, a new cloning system,
      which facilitates the efficient high-throughput production of hpRNAi constructs
      using clones from the C. elegans ORFeome library. The combined use of pWormgate2
      and the ORFeome library, with a recently developed particle bombardment
      transformation system, expedites hpRNAi gene silencing. This will be particularly
      useful for studying those genes that are refractory to the effects of injected or
      fed dsRNA, such as neural genes. We report the efficient production of hpRNAi
      constructs using pWormgate2 and also the knockdown of selected genes, including
      neurally expressed genes that have previously been refractory to RNAi. Further,
      when combined with the rrf-3 RNAi hypersensitive strain, the Wormgate approach
      delivered a highly penetrant knockdown phenotype in nearly 100% of worms for a
      gene that was completely refractory to other RNAi delivery methods.

PMID- 15994031
TI  - Differentiation of five strains of infectious bursal disease virus: development
      of a strain-specific multiplex PCR.
AB  - Infectious bursal disease virus (IBDV) is a major cause of disease problems in
      the poultry industry and vaccination has therefore been applied intensively to
      control the infection. The classical methods of detection and characterization of
      IBDV are by the use of immunodiffusion test and histopathology. Since these
      methods are laborious and have low specificity alternatives are needed. In the
      present study, we report the development of a strain-specific multiplex RT-PCR
      technique, which can detect and differentiate between field strains of IBDV and
      vaccine virus strains including a so-called hot vaccine strain widely used in the
      European poultry industry. The method, which is highly specific, fast and
      inexpensive, can be applied in all laboratories with basal PCR capabilities and
      equipment.

PMID- 15994032
TI  - Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2
      and CYP2E1.
AB  - The present study examined accumulation of the metal toxins cadmium (Cd) and lead
      (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and
      concentrations of zinc and copper in liver and kidney samples using
      immunoblotting coupled with metal analysis. The post mortem liver and kidney
      cortex samples were from 23 males and 8 females aged 3-89 years. All were
      Caucasians who had not been exposed to metals in the workplace. Average kidney
      cortex Cd load of 17.4 microg/g w.w. was 17 times greater than average liver Cd
      load (1.1 microg/g w.w.). In contrast, average kidney cortex Pb load of 0.09
      microg/g w.w. was two times lower than liver Pb load of 0.19 microg/g w.w.
      Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33%
      lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney
      Pb loads, correlated positively with donors' age. After controlling for liver Cd
      load, an inverse correlation was seen between Zn and age (partial r=-0.39,
      P=0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein
      abundance correlated with age-adjusted Cd load (partial r=0.37, P=0.02) whereas
      kidney CYP4F2 protein abundance showed a positive correlation with age-adjusted
      Cd loads (partial r=0.40, P=0.02). These findings suggest that Cd may be an
      inducer of renal CYP4F2 and hepatic CYP2E1 and that increased renal CYP4F2
      expression may implicate in Cd-linked renal tubular dysfunction and high blood
      pressure, involving CYP4F2-dependent arachidonic acid metabolism.

PMID- 15994033
TI  - Investigations on cellular proliferation induced by zearalenone and its
      derivatives in relation to the estrogenic parameters.
AB  - Many man-made chemicals (pesticides) and naturally occurring compounds
      (mycotoxins and phytoestrogens) can enter the food chain and bind to estrogen
      receptors (ERs). Mycotoxins, including zearalenone (ZEA) and its derivatives, can
      occur worldwide in cereals and cause several health disorders. In order to
      characterize the estrogenic activity of zearalenone and its derivatives (alpha
      zearalenol (alpha-ZEA), beta-zearalenol (beta-ZEA), alpha-zearalanol (alpha-ZAL)
      and beta-zearalanol (beta-ZAL)), the proliferation of ER-positive (MCF-7) and ER
      negative (MDA-MB-231) human breast cancer cell lines was measured. After exposure
      at levels ranging from 0.1 pM to 0.1microM, cell proliferation (E-screen assay)
      was evaluated by MTT test through estrogenic parameters. On the MCF-7 cell line,
      estrogenic concentration that induced 50% cellular proliferation (EC(50)) of beta
      zearalenol was statistically higher (5.2 x 10(-3)microM) than those of other
      zearalenone-related compounds, in agreement with other authors. All mycotoxins
      showed similar estrogenic parameters, with the exception of alpha-zearalenol that
      induced a higher proliferative effect (PE=2.6) and relative proliferative potency
      (RPP=7). Since MCF-7 contains both ERalpha and ERbeta-positive cells, at the mRNA
      and protein level, the estrogenic activity induced by mycotoxins may be ER
      mediated, particularly through ERalpha that was the predominant ER subtype in
      these cells. A partial antagonism of mycotoxin-related estrogenic proliferation
      was seen when tamoxifen was used, confirming a receptor-dependent estrogenic
      response. MDA-MB-231 cells did not show ERs and after exposure to mycotoxins or
      17beta-estradiol marginal PE values related to growth variability of MDA-MB-231
      were found. Further studies are needed to understand in human tissues the
      mechanisms of action of ZEA and its derivatives that may be found as contaminants
      in the human diet.

PMID- 15994034
TI  - Pharmacokinetics of monobutylphthalate, the active metabolite of di-n
      butylphthalate, in pregnant rats.
AB  - Di-n-butylphthalate (DBP) is a phthalic acid ester used as a plasticizer and
      solvent. DBP is a developmental toxicant in rats and mice, with adverse effects
      arising from the monoester metabolite monobutyl phthalate (MBP). The objective of
      this study was to evaluate the pharmacokinetics of MBP and monobutyl phthalate
      glucuronide (MBP-G) in pregnant rats following intravenous (i.v.) dosing with
      MBP. Pregnant dams were i.v. dosed with aqueous MBP (10, 30, or 50mg MBP/kg body
      weight) on gestation day (GD) 19. The pharmacokinetics of MBP and MBP-G were
      rapid: MBP was metabolized to MBP-G within 5 min, and MBP and MBP-G disappeared
      from maternal and fetal plasma within 24h of dosing. Results were consistent with
      two previous studies that utilized oral doses of DBP, suggesting that chemical
      (DBP versus MBP), vehicle (oil versus aqueous), dose level, and route (oral
      versus i.v.) have minimal effects on the maternal pharmacokinetics of MBP and MBP
      G. This study provides direct pharmacokinetic analysis for MBP and MBP-G in
      pregnant rats during fetal male reproductive development, and indicates that
      future pharmacokinetic or toxicology studies can reliably utilize oral dosing
      with DBP.

PMID- 15994035
TI  - Bone density measured by dual energy X-ray absorptiometry in Qatari women.
AB  - BACKGROUND: Over the past 10 years, osteoporosis has emerged as a major public
      health problem. It is characterized by low bone mass with micro architectural
      deterioration of bone tissue resulting in increase bone fragility and
      susceptibility to fractures. Bone mineral density measurements are widely used to
      diagnose osteoporosis and to assess its severity. Commercial dual-energy X-rays
      absorptiometry (DXA) scanners used to determine bone mineral density (BMD)
      contains reference data for different populations. AIM: The aim of this study was
      to determine reference values for Qatari female population and to compare them
      with values from western and other Arab countries. METHODS: A cross-sectional
      study of 574 Qatari women aged between 20 and 69 years was carried out using DXA
      scan to establish reference values of bone mineral density. Measurements were
      taken at the lumbar spine and proximal femur. The data were compared with
      normative taken by Caucasians, Kuwaiti, Lebanese and Saudi women over five
      decades of age. RESULTS: Our results showed that the Qatari subjects showed the
      expected decline in BMD at spinal sites with age after peaking at 30-39 years age
      group, and for femoral site at 40-49 years. The BMD values of the spine of Qatari
      women were lower than Caucasian and Kuwaiti women but higher than the Lebanese
      and similar to Saudi women. The BMD values of the total femur were higher in
      Qatari females than Caucasians, Kuwaitis, Lebanese and Saudis in the age group of
      40-59, but lower in the age group 60-69 years. Of the 147 studied Qatari women in
      the age group (50-69) years, the T-score was normal (>-1 S.D.) in 79 subjects
      (53.7%), in the osteopenic range (-1 to -2.5 S.D.) in 51 subjects (34.7%) and in
      the osteoporotic range (<-2.5 S.D.) in 17 subjects (11.6%). CONCLUSION: BMD value
      of Qatari females are lower than Caucasians and Kuwaitis at the spine, and at the
      total femur in the age group 60-69 years, but higher values of total femur in the
      age group 40-59 years. Osteoporosis is common among menopausal Qatari women and
      should be considered a matter of public concern.

PMID- 15994036
TI  - WITHDRAWN: Actions of a fungal keratinase and reducing agents on the nail plate.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 15994037
TI  - Cross-linking of dried paracetamol alginate granules Part 1. The effect of the
      cross-linking process variables.
AB  - This paper reports on the cross-linking of dried (<5% moisture) paracetamol
      alginate granules with calcium chloride solutions. The effect of calcium
      concentration, temperature of the treatment solution, stirring speed and time
      used during cross-linking of granules on water uptake by the granules during
      cross-linking and physical properties of the cross-linked and dried granules were
      studied. A full factorial study of these factors each at two levels was used
      (CaCl2.2H2O: 20, 100 mg/ml; temperature: 25, 45 degrees C; stirrer speed: 25, 240
      rpm; time: 1.5 and 5.5 min) to treat dried stock granules (size: 0.8-1.0 mm)
      containing the model drug paracetamol and sodium alginate powder (1:1) which were
      prepared using conventional aqueous granulation under low shear. In addition to
      SEM and photomicrography, the physical properties studied were water uptake
      during cross-linking, yield, aggregation behaviour, moisture content, drug
      content, early stage drug release [over 10 s (R10) and the next 50 s (R50)] and
      calcium and sodium content of the unwashed cross-linked granules. Dry granules
      were successfully cross-linked. The treatment factors significantly affected most
      of the response variables. The variables most affected were water uptake (78
      254%), drug entrapment (58-86%), early release (R10: 1.2-6.4% and R50: 3.0
      12.2%), granule aggregation (0-70%), calcium (6.02-12.4%) and sodium content (1.2
      6.44%). SEM photographs suggest that low calcium treated granules were less
      porous in nature compared to high calcium treated granules. Low shear drug
      alginate granules can be cross-linked in dried state. The properties of the cross
      linked granules can be modified by altering the treatment process.

PMID- 15994038
TI  - The aphrodisiac herb Tribulus terrestris does not influence the androgen
      production in young men.
AB  - OBJECTIVE: The aim of the current study is to investigate the influence of
      Tribulus terrestris extract on androgen metabolism in young males. DESIGN AND
      METHODS: Twenty-one healthy young 20-36 years old men with body weight ranging
      from 60 to 125 kg were randomly separated into three groups-two experimental
      (each n=7) and a control (placebo) one (n=7). The experimental groups were named
      TT1 and TT2 and the subjects were assigned to consume 20 and 10 mg/kg body weight
      per day of Tribulus terrestris extract, respectively, separated into three daily
      intakes for 4 weeks. Testosterone, androstenedione and luteinizing hormone levels
      in the serum were measured 24 h before supplementation (clear probe), and at 24,
      72, 240, 408 and 576 h from the beginning of the supplementation. RESULTS: There
      was no significant difference between Tribulus terrestris supplemented groups and
      controls in the serum testosterone (TT1 (mean+/-S.D.: 15.75+/-1.75 nmol/l); TT2
      (mean+/-S.D.: 16.32+/-1.57 nmol/l); controls (mean+/-S.D.: 17.74+/-1.09 nmol/l)
      (p>0.05)), androstenedione (TT1 (mean+/-S.D.: 1.927+/-0.126 ng/ml); TT2 (mean+/
      S.D.: 2.026+/-0.256 ng/ml); controls (mean+/-S.D.: 1.952+/-0.236 ng/ml) (p>0.05))
      or luteinizing hormone (TT1 (mean+/-S.D.: 4.662+/-0.274U/l); TT2 (mean+/-S.D.:
      4.103+/-0.869U/l); controls (mean+/-S.D.: 4.170+/-0.406U/l) (p>0.05)) levels. All
      results were within the normal range. The findings in the current study
      anticipate that Tribulus terrestris steroid saponins possess neither direct nor
      indirect androgen-increasing properties. The study will be extended in the
      clarifying the probable mode of action of Tribulus terrestris steroid saponins.

PMID- 15994039
TI  - Ethnographic component and organism documentation in an ethnopharmacology paper:
      a "minimum" standard.
AB  - The ethnographic component (traditional/indigenous therapeutic uses of plants or
      animals, specific contexts of use, preparation, dosage, route of administration)
      published in the Journal of Ethnopharmacology (JEP) has not been consistently and
      fully provided in the past. In an attempt to ensure the fulfillment of these
      criteria, hence, the fulfillment of the scope of papers published in this
      journal, starting with the February, 2004 issue of JEP (vol. 90, 2004), the
      journal provided detailed "Guide to Authors", "Author Checklist", and models of
      ethnopharmacology papers. An analysis of research papers published in JEP vols.
      98 and 99 showed that these papers still have not achieved full compliance with
      the interdisciplinarity/multidisciplinarity nature of the journal, and the
      discipline. Thus, a minimum standard for the ethnographic component is set down.

PMID- 15994040
TI  - Oleanolic acid and ursolic acid: research perspectives.
AB  - Oleanolic acid and ursolic acid are ubiquitous triterpenoids in plant kingdom,
      medicinal herbs, and are integral part of the human diet. During the last decade
      over 700 research articles have been published on their research, reflecting
      tremendous interest and progress in our understanding of these triterpenoids.
      This included the isolation and purification of these tritepernoids from various
      plants and herbs, the chemical modifications to make more effective and water
      soluble derivatives, the pharmacological research on their beneficial effects,
      the toxicity studies, and the clinical use of these triterpenoids in various
      diseases including anticancer chemotherapies. A briefly commentary is attempted
      here for their research perspectives.

PMID- 15994041
TI  - Riding the wave: South Africa's contribution to ethnopharmacological research
      over the last 25 years.
AB  - South Africa is a country with both rich floral biodiversity and cultural
      diversity. Traditional herbal medicines form an important part of the healthcare
      of most South Africans, and relies heavily on the use of indigenous plants. This
      article briefly describes the role South Africa has played in recent years, in
      contributing to the worldwide increase in research in the field of
      ethnopharmacology.

PMID- 15994042
TI  - Anxiolytic effects of Salvia reuterana Boiss. on the elevated plus-maze model of
      anxiety in mice.
AB  - The anxiolytic and sedative effects of hydroalcoholic extract (HE) of Salvia
      reuterana Boiss. was evaluated in mice. The HE of Salvia reuterana (100 mg/kg),
      increased the percentage of time-spent and the percentage of arm entries in the
      open arms of the elevated plus-maze. Spontaneous locomotor activity count
      measured in 15 min of the test was significantly decreased in animals pretreated
      with diazepam and 100 mg/kg of Salvia reuterana extract. Results of the present
      study provide support for the traditional usage of Salvia reuterana as a sedative
      and anxiolytic medicinal plant.

PMID- 15994043
TI  - Past and future contributions to traditional medicine in the health care system
      of the Middle-East.
AB  - Due to the rich cultural heritage and relatively rich flora, a wealth of
      knowledge on traditional and folk medicine has been accumulated in the Middle
      East. However, except Turkey, the number of ethnobotanical field studies is few
      and mainly focused on Unani medicine, which is practised widespread in the
      southern communities. Urgent scientific field surveys should be conducted among
      the native people in order to document the wealth of knowledge on folk medicine,
      other than Unani medicine, before it will be lost by the erosive effects of
      modernization.

PMID- 15994044
TI  - Gastric antiulcer and anti-inflammatory activities of the essential oil from
      Casearia sylvestris Sw.
AB  - To investigate the antiulcer and antiinflammatory activities of the essential oil
      from Casearia sylvestris leaves (EOCS) the following tests were used: rat paw
      edema, granulomatous tissue test, vascular permeability, writhing test, gastric
      ulcer stress-induced and evaluation of gastric secretion (pylorus ligation test).
      The total yield of EOCS was 2.5% with LD50 of 1100 mg/kg in mouse. The major
      compounds identified using gas chromatography were caryophyllene, thujopsene,
      alfa-humulene, beta-acoradiene, germacrene-d, bicyclogermacrene, calamenene,
      germacrene B, spathulenol and globulol. The EOCS orally administered to the rats
      at 125 mg/kg resulted 36% of inhibition in carrageenan-induced edema in the rat
      paw assay (p<0.05, Student's t-test). However, both rat paw edema dextran-induced
      and vascular permeability assay using histamine showed no significant inhibition.
      Mice submitted to the writhing test using acetic acid presented 58% and 56% of
      inhibition in writhes with EOCS and indomethacin, respectively. Furthermore, EOCS
      inhibited 90% of stress-induced gastric ulcer, while cimetidine inhibited 70%
      (p<0.05, Student's t-test). The volume of gastric secretion in the group treated
      with EOCS was greater than the group treated with cimetidine. The EOCS also
      showed no changes related to H+ levels in the gastric secretion. With the overall
      results obtained in this study the authors suggest an anti-inflammatory activity
      for the EOCS of Casearia sylvestris beyond its anti-ulcer activity.

PMID- 15994045
TI  - Effects of brazilin on the production of fructose-2,6-bisphosphate in rat
      hepatocytes.
AB  - Increased hepatic glucose output is one of the major mechanisms of hyperglycemia
      in diabetic patients. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic
      intermediate, plays a critical role in hepatic glucose output by regulating
      gluconeogenesis and glycolysis in the liver. Brazilin, an active component of
      sappan wood (Caesalpinia sappan), decreases blood glucose in diabetic animals. In
      this study, the effect of brazilin on gluconeogenic intermediate production and
      enzyme activity were examined to investigate the hypoglycemic mechanism of
      brazilin. Brazilin increased the production of F-2,6-BP in hepatocytes by
      elevating intracellular levels of fructose-6-phosphate (F-6-P) and hexose-6
      phosphate (H-6-P). Brazilin was also found to significantly increase the activity
      of 6-phosphofructo-2-kinase (PFK-2) and pyruvate kinase in glucagon-treated
      hepatocytes. However, glucose-6-phosphatase activity was not affected by
      brazilin. This data suggests that brazilin inhibits hepatic gluconeogenesis by
      elevating the F-2,6-BP level in hepatocytes, possibly by elevating cellular F-6
      P/H-6-P levels and PFK-2 activity. Increased pyruvate kinase activity may also
      play a role in the anti-gluconeogenic action of brazilin.

PMID- 15994046
TI  - The value of ultrasonographic measurement in carpal tunnel syndrome in patients
      with negative electrodiagnostic tests.
AB  - The diagnosis of carpal tunnel syndrome (CTS) is mainly based on clinical
      findings and electrodiagnostic tests (EDT). However, EDT results do not support
      clinical findings in some cases. It has been recently suggested that
      ultrasonography (US) can be used to diagnose CTS. In this study, we aimed to
      investigate whether US has a diagnostic value for CTS in patients with negative
      EDT findings or not. EDT was performed on 319 wrists with clinical CTS findings
      in electrophysiology laboratory. Median and ulnar nerve conduction velocities
      were measured in all cases and electromyography was performed in patient with
      tenar atrophy and having suspicion involvement of brachial plexus as EDT. Fifty
      nine wrists with negative EDT (study group) and 30 wrists from 15 healthy
      individuals (control group) were examined using US. The mean of cross-sectional
      areas (CSAs) measurements were found 8.83+/-3.05 mm2 by tracing method (TM) and
      8.51+/-3.13 mm2 by ellipsoid formula (EF) in study group, and 7.63+/-1.52 mm2 by
      TM and 7.66+/-1.42 mm2 by EF in control group. The differences between study
      group and control group according to both TM and EF were significant (t-test
      p=0.0079, p=0.0460, respectively). In study group, CSAs were larger than 10.5 mm2
      in 18 (30.51%) and 16 (27.12%) wrists according to TM and EF findings,
      respectively, and in only one wrist (3.33%) in control group by both TM and EF.
      The differences of ultrasonographic CTS numbers between study group and control
      group were significant (p=0.0024 by TM, p=0.0086 by EF). We confirmed the
      usefulness of quantitative US assessment in the diagnosis of CTS in the patients
      with negative EDT findings. If EDT findings are inadequate to confirm the CTS in
      the patients with clinical CTS, US studies may be helpful to diagnose.

PMID- 15994047
TI  - Assessment of RAISUS, a novel system for identification and antimicrobial
      susceptibility testing for enterococci.
AB  - RAISUS, a system developed by Nissui Pharmaceutical (Tokyo, Japan), is a novel
      fully automated system for rapid identification and antimicrobial susceptibility
      testing. The aim of this study was to compare RAISUS with VITEK systems and
      microdilution tests based on the National Committee for Clinical Laboratory
      Standards, with regard to the identification and susceptibility of 64
      enterococci. The agreement rate between RAISUS and VITEK was 98.4% (63/64) for
      bacterial identification. One strain was identified as E. faecalis by RAISUS, but
      as E. faecium by VITEK. Regarding susceptibility tests, the range of essential
      agreement and agreement in clinical categories for RAISUS and VITEK ranged from
      70.3% to 95.3% and from 68.8% to 96.9%, respectively. Results of antimicrobial
      susceptibility testing for vancomycin (VAN) showed very major, major, and minor
      errors in 0%, 3.1% (2/64), and 0%, respectively. RAISUS could provide reports of
      detection of VAN-resistant enterococci (VRE) within 5 h by using fluorogenic
      substances and redox. In conclusion, RAISUS could be useful in a clinical setting
      because it allows rapid identification of enterococci and the potential ability
      to detect VRE more promptly than the VITEK system.

PMID- 15994048
TI  - Molecular detection and serotypic characterization of dengue viruses by single
      tube multiplex reverse transcriptase-polymerase chain reaction.
AB  - This study was designed to develop a reverse transcriptase-polymerase chain
      reaction (RT-PCR)-based rapid and cost-effective diagnostic test for detection as
      well as serotypic characterization of dengue viruses in the acute phase of
      illness. In this regard, 2 methods of RT-PCR, namely, 2-step nested RT-PCR and 1
      tube multiplex RT-PCR, have been evaluated. One-tube multiplex RT-PCR was found
      superior; thus, its sensitivity and specificity were compared with gold standard
      "cell culture". In the present study, serum samples of all individuals were
      evaluated by cell culture and RT-PCR. Of 200 clinically suspected patients
      tested, 66 were found to be positive for the dengue virus RNA and could be
      successfully characterized into the serotypes. Of these 66, 62 patients were
      found to be serologically positive by Dengue Duo IgM and IgG Rapid Strip test
      (Pan Bio, Windsor, Australia). The sensitivity of the cell culture procedure was
      found to be lower; 63% as compared with multiplex RT-PCR, with predictive value
      of positive test being 100% and predictive value of negative test being 84.8%.
      Specificity was found to be 100% for both the assays. It is thus proposed that 1
      tube multiplex RT-PCR-based assay would prove to be an extremely useful tool for
      routine laboratory diagnosis.

PMID- 15994049
TI  - Nonfatal pulmonary Trichoderma viride infection in an adult patient with acute
      myeloid leukemia: report of one case and review of the literature.
AB  - Trichoderma species have been recognized to be pathogenic in immunosuppressed
      hosts with increasing frequency. Trichoderma species are responsible for
      continuous ambulatory peritoneal dialysis associated peritonitis and infections
      in immunocompromised patients with a hematologic malignancy or solid organ
      transplantation. Trichoderma longibrachiatum is the most common species involved
      in these infections. We report the first case of nonfatal pulmonary infection
      caused by Trichoderma viride in leukemia patient. It had a successful answer to
      new antifungal agents as voriconazole and caspofungin. Trichoderma viride was
      isolated from pulmonary aspirate culture from a 54-year-old female who had
      received chemotherapy for acute myeloid leukemia. The minimal inhibitory
      concentrations for the organism were the following: amphotericin B (0.25
      microg/mL) and voriconazole (2 microg/mL). Initially, she was treated
      unsuccessful with liposomal amphotericin B and voriconazole and caspofungin were
      added later. The patient is alive. We report one case along review of the
      literature.

PMID- 15994050
TI  - Comparison of 9 different PCR primers for the rapid detection of severe acute
      respiratory syndrome coronavirus using 2 RNA extraction methods.
AB  - The sensitivity and specificity of various severe acute respiratory syndrome
      coronavirus (SARS-CoV) PCR primer and probe sets were evaluated through the use
      of commercial kits and in-house amplification formats. Conventional and real-time
      PCR assays were performed using a heat-block thermocycler ABI 9600, the Roche
      LightCycler version 1.2, or the ABI 7000 Sequence Detection System. The
      sensitivity of all primers was between 0.0004 and 0.04 PFU with viral cell lysate
      and between 0.004 and 0.4 PFU in spiked stool specimen per PCR assay. The primer
      sets for real-time PCR assays were at one least 1 log more sensitive than the
      primer sets used in the conventional PCR. A panel of viruses including swine
      gastroenteritis virus, bovine coronavirus, avian bronchitis virus (Connecticut
      strain), avian bronchitis virus (Massachusetts strain), human coronaviruses 229E
      and OC43, parainfluenza virus (type III), human metapneumovirus, adenovirus,
      respiratory syncytial virus, and influenza A were tested by all assays. All real
      time PCR assays used probe-based detection, and no cross-reactivity was observed.
      With conventional PCR, analysis was performed using agarose gel electrophoresis
      and multiple nonspecific bands were observed. Two commercial extraction methods,
      magnetic particle capture and silica-based procedure were evaluated and the
      results were comparable. The former was less laborious with shorter time for
      completion and can easily be adapted to an automated system such as the MagNa
      Pure-LC, which can extract nucleic acid from clinical samples and load it into
      the sample capillaries of the LightCycler. As exemplified by this study, the
      continued refinement and evaluation of PCR procedures will greatly benefit the
      diagnostic laboratory during an outbreak of SARS.

PMID- 15994051
TI  - Acridine orange leukocyte cytospin test for central venous catheter--related
      bloodstream infection: a pediatric experience.
AB  - The aim of this study was to evaluate the acridine orange leukocyte cytospin
      (AOLC) test for the rapid diagnosis of septicemia caused by central venous
      catheters (CVCs), without removing the catheter, in a pediatric intensive care
      unit population. Twenty-six patients admitted in the pediatric intensive care
      unit of Azienda Ospedaliera "Ospedali Riuniti di Bergamo", Italy, were
      prospectively evaluated for CVC-related infection. Blood for culture was taken
      from all patients. Quantitative endoluminal cultures of the removed catheter tip
      by Cleri's technique and semiquantitative superficial cultures of the hub were
      performed. Gram staining and an AOLC smear were done according to Kite's
      technique. Four Staphylococcus CVC-related bloodstream infections were
      identified. CVC colonization was detected in 8 patients. Four had septicemia
      (Enterococcus faecalis, Escherichia coli, Klebsiella oxytoca, Candida glabrata)
      without CVC involvement. However, Gram staining and the AOLC test were negative
      in all cases. We conclude that cytocentrifugation and acridine orange staining of
      blood withdrawn by Kite's method from an in situ catheter, although simple,
      quick, and inexpensive, did not aid diagnosis in this pediatric population.

PMID- 15994052
TI  - Prevalence of decreased susceptibility to carbapenems among Serratia marcescens,
      Enterobacter cloacae, and Citrobacter freundii and investigation of
      carbapenemases.
AB  - Between March and July 2002, total of 612 clinical isolates of Serratia
      marcescens, Enterobacter cloacae, and Citrobacter freundii (201 S. marcescens,
      228 E. cloacae, and 183 C. freundii) were collected from 13 clinical laboratories
      in a nationwide distribution. Imipenem and meropenem minimum inhibitory
      concentrations (MICs) were determined using the agar dilution method according to
      the National Committee for Clinical Laboratory Standards guidelines. For the
      isolates with a decreased susceptibility to carbapenems (MICs of >or=2
      microg/mL), isoelectric focusing, polymerase chain reaction (PCR) amplification
      of the carbapenemase genes (bla(IMP-1), bla(VIM-2), bla(SME-1), bla(OXA-23),
      bla(OXA-25), bla(KPC-1)), and sequencing were performed. The prevalence of S.
      marcescens, E. cloacae, and C. freundii with a decreased susceptibility to
      imipenem was 17.9% (36/201), 0.4% (1/228), and 0.5% (1/183), respectively, and to
      meropenem, it was 11.4% (23/201), 0% (0/228), and 0.5% (1/183), respectively. The
      bla(VIM-2) was the only carbapenemase detected, and was found in 0.5% (1/201) of
      S. marcescens and 0.5% (1/183) of C. freundii isolate.

PMID- 15994053
TI  - Activated protein C attenuates acute ischaemia reperfusion injury in skeletal
      muscle.
AB  - Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory
      properties. The purpose of the present study was to evaluate the effects of
      activated protein C in the setting of skeletal muscle ischaemia reperfusion
      injury (IRI). IRI was induced in rats by applying rubber bands above the levels
      of the greater trochanters bilaterally for a period of 2h followed by 12h
      reperfusion. Treatment groups received either equal volumes of normal saline or
      activated protein C prior to tourniquet release. Following 12h reperfusion,
      muscle function was assessed electrophysiologically by electrical field
      stimulation. The animals were then sacrificed and skeletal muscle harvested for
      evaluation. Activated protein C significantly attenuated skeletal muscle
      reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio
      and electrical properties of skeletal muscle. Further in vitro work was carried
      out on neutrophils isolated from healthy volunteers to determine the direct
      effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated
      neutrophils were examined by measuring CD18 expression as well as reactive oxygen
      species generation. The in vitro work demonstrated a reduction in CD18 expression
      and reactive oxygen species generation. We conclude that activated protein C may
      have a protective role in the setting of skeletal muscle ischaemia reperfusion
      injury and that this is in part mediated by a direct inhibitory effect on
      neutrophil activation.

PMID- 15994054
TI  - Lag screws for hip fracture fixation: Evaluation of migration resistance under
      simulated walking.
AB  - Previous mechanical studies concerning cut-out of lag screws for pertrochanteric
      hip fractures have relied on static or dynamic uniaxial loading regimens to
      induce construct failure by varus collapse and superior cut-out. However, the hip
      is loaded in a multiplanar, dynamic manner during normal gait. We designed a hip
      implant performance simulator (HIPS) system to evaluate lag screw cut-out under
      multiplanar loading representative of normal gait. Five surrogate pertrochanteric
      fracture specimens with lag screw fixation were loaded up to 20,000 cycles using
      a biaxial rocking motion (BRM) gait simulation protocol. Another five specimens
      were loaded using a standard uniaxial loading protocol. The BRM loading group
      exhibited combined varus collapse (5.4+/-2.9 degrees ) and backward rotation
      (7.2+/-2.8 degrees ). The uniaxial loading group exhibited four times less varus
      collapse (1.4+/-1.1 degrees ) as compared to the BRM group, and only negligible
      rotation. For correlation of lag screw migration in surrogate specimens to that
      in native bone, six human cadaveric specimens were subjected to BRM loading. The
      degree of varus collapse (8.5+/-7.7 degrees ) and rotation (7.2+/-6.4 degrees )
      in cadaveric specimens were comparable to that in surrogate specimens, with the
      surrogate specimens showing significantly less variability. The results
      demonstrate that accounting for clinically realistic multiplanar loading vectors
      significantly affects implant migration, and therefore should be considered when
      evaluating the fixation strength of hip screw implants.

PMID- 15994055
TI  - Relationship of bone morphogenetic protein expression during osteoblast
      differentiation to wild type p53.
AB  - We have previously shown p53 to have a specific role in osteoblast
      differentiation by its ability to regulate expression of certain bone specific
      proteins. In this study, we show mineralized matrix formation in vivo to be
      directly related to the presence of wild type p53 in osteoblastic osteosarcoma
      cells. In order to further understand the importance of p53 in differentiation,
      we investigated the relationship between p53 and Bone Morphogenetic Proteins
      (BMPs) (BMP 1, 2, 3A, 3B (GDF-10), 4, 5, 6, 7, 8A and 8B) during osteoblast
      differentiation. The expression of several BMPs were tested using RNase
      Protection Assay in differentiating ROS17/2.8 osteoblastic osteosarcoma cells.
      The expression of BMPs 1, 2, 3a, 3b and 7 showed time dependent modulation during
      in vitro differentiation. In order to determine if p53 has a role in this
      process, we used a murine osteosarcoma cell line stably expressing a temperature
      sensitive p53. Cells were exposed to ascorbic acid and glycerophosphates to
      hasten in vitro osteoblast differentiation and maintained either at 32 or 37
      degrees C for expression of the wild type or mutant p53 phenotype. The expression
      of BMP-2, BMP-4 and BMP-7 were modulated in a p53 dependent fashion. We were able
      to confirm the p53 dependency of BMP-2 independently by RT-PCR. While BMP-2
      expression was evident in the presence of both wild type and mutant p53,
      regulated expression was seen only in cells expressing wild type p53. Transient
      over expression of wild type p53 did not result in the same BMP-2 response as
      stable expression showing that the presence of p53 may be important for an
      orderly development of osteoblast differentiation rather than a direct effect on
      gene expression. The functional relationship between p53 and these bone specific
      markers is discussed.

PMID- 15994056
TI  - Illness stories on the Internet: features of websites disclosing breast cancer
      patients' illness stories in the Dutch language.
AB  - OBJECTIVE: To examine the way in which breast cancer patients' illness stories in
      the Dutch language are disclosed on the Internet. METHODS: Websites containing
      Dutch illness stories written by breast cancer patients were selected using a
      search engine on the Internet. A checklist was developed based on a theoretical
      framework for analysing communication processes in order to examine the selected
      websites. RESULTS: None of the websites implements search facilities based on
      either the content of an illness story, or the personal features of the author. A
      minority of the websites offers information about the illness stories, such as
      author's genuineness and editor's review. CONCLUSION: The Internet's
      opportunities are not fully utilized with respect to disclosing breast cancer
      patients' illness stories. PRACTICE IMPLICATIONS: In order to support a patient
      in finding appropriate illness stories in the diverse set of available stories,
      we are in the process of developing an application that combines symbolic and
      statistical natural language analysis techniques to facilitate content-based
      retrieval.

PMID- 15994057
TI  - Care staff attributions about challenging behaviors in adults with intellectual
      disabilities.
AB  - A number of researchers have explored the attributions that care staff make about
      challenging behavior. The expectation, based on behavioral and cognitive models,
      is that these attributions may help predict why staff inadvertently reinforce
      challenging behavior. Two studies of staff attributions about challenging
      behavior are reported. In the first, a high level of consistency in attributions
      across staff was found. In a second quasi-experimental study, staff made
      attributions about two known clients' behavior. Analysis of these data showed
      that attributions varied in a manner broadly consistent with the hypothesized
      functions of the behaviors. The weight of the evidence suggests that staff may be
      sensitive to the causes of challenging behavior. The practical implications of
      these data are discussed.

PMID- 15994059
TI  - Transient left paraduodenal hernia.
AB  - A 52-year-old woman with acute deterioration of recurrent abdominal pain was
      admitted to the hospital. Spiral computed tomography (CT) of abdomen was
      performed. A left paraduodenal hernia was identified on CT. There was no clinical
      sign or imaging finding suggesting intestinal obstruction or mesenteric ischemia.
      She refused surgical intervention since her pain was intermittant and decreasing.
      On the fifth day of hospitalization the patient's pain resolved completely and
      the follow-up CT demonstrated regression of the herniation.

PMID- 15994058
TI  - Perinatal AZT exposure alters the acoustic and tactile startle response to 8-OH
      DPAT and apomorphine in adult rats.
AB  - The present study was designed to assess the dopaminergic and serotonergic
      contributions of the acoustic startle response (ASR) and the tactile startle
      response (TSR) in adult rats that had been perinatally exposed to AZT
      (azidothymidine, zidovudine; an antiretroviral agent). Each dam was randomly
      assigned to a treatment group: non-treated, AZT0, 100 or 150 mg/kg. Once daily
      gastric intubation began prenatally on gestational day (G) 19 and continued to
      G22 and then the pups were intubated between postnatal day (PND) 2-20. On PND60,
      animals were tested for responses to both acoustic and tactile stimuli following
      a challenge of vehicle, 0.25 or 0.5 mg/kg 8-OH-DPAT, a 5-HT(1A) agonist, or 0.75
      or 2.0 mg/kg apomorphine (APO, a dopaminergic agonist) IP. Both DPAT and APO
      increased startle magnitude as expected. Additionally, perinatal AZT exposure
      enhanced startle responses following both DPAT and APO, an effect not due to
      perinatal handling or intubation. Similarly, perinatal AZT increased tactile
      responses following drug challenge in a gender-specific manner. Perinatal AZT
      also prolonged startle latencies, a change which may indicate that perinatal AZT
      alters conduction velocity. Therefore, the administration of AZT during the
      perinatal period results in long-term functional alterations within the startle
      reflex pathways.

PMID- 15994060
TI  - A maximum likelihood expectation maximization algorithm with thresholding.
AB  - The maximum likelihood expectation maximization (MLEM) algorithm has several
      advantages over the conventional filtered back-projection (FBP) for image
      reconstruction. However, the slow convergence and the high computational cost for
      its practical implementation have limited its clinical applications. This study
      proposes the incorporation of a thresholding technique in both the MLEM and
      ordered subsets EM (OSEM) algorithm to accelerate convergence. The threshold is
      set to c*m, where m is the mean pixel value of the whole image. The
      reconstruction time is proportional to the total number of pixels, so a
      thresholding technique that nullifies the value of a pixel if it falls below a
      threshold, can effectively remove the non-active pixels and substantially
      accelerate reconstruction. Preliminary tests on simulated PET data reveal that
      the thresholding technique accelerates the convergence rate and reduce error in
      the reconstructed image. The reconstruction performance improves with the
      increase of the threshold level and the MSE reaches minimum for c value equals to
      about 1.

PMID- 15994061
TI  - Treatment and outcome of autoimmune hematologic disease in common variable
      immunodeficiency (CVID).
AB  - Common variable immunodeficiency (CVID) is associated with autoimmunity, most
      commonly immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia
      (AIHA). In a retrospective chart review of 326 CVID patients, 35 (11%) patients
      had a history of autoimmune hematologic disease. Fifteen patients had ITP, 9 had
      AIHA, and 11 had Evans syndrome (both ITP and AIHA). The age at diagnosis for
      CVID ranged from 5 to 66 years and for autoimmunity, from 2 to 66 years. There
      were 16 males and 19 females. Nineteen patients (54%) had the first episode of
      thrombocytopenia or hemolytic anemia prior to the diagnosis of immunodeficiency,
      11 (32%) were diagnosed concurrently, and 5 (14%) developed one or both of these
      autoimmune diseases following the diagnosis of CVID. Eight patients were known to
      have granulomatous changes in one or more organs. Treatments for autoimmunity
      included corticosteroids, anti-Rh immunoglobulin, and intravenous immunoglobulin;
      11 patients underwent splenectomy. While 5 patients had recurrences of autoimmune
      hemolytic disease while receiving maintenance intravenous immunoglobulin, most
      episodes occurred for subjects not yet on this therapy (P < 0.0001). Most
      patients with frequent infections and hematologic autoimmunity should be
      evaluated for CVID.

PMID- 15994062
TI  - Clinical and EEG phenotypes of epilepsy in the baboon (Papio hamadryas spp.).
AB  - Spontaneous seizures have been reported in several baboon subspecies housed at
      the Southwest Foundation for Biomedical Research (SFBR), including Papio
      hamadryas anubis as well as cynocephalus/anubis and other hybrids. This study
      classified clinical and electroencephalographic (EEG) phenotypes in these
      subspecies based upon interictal and ictal findings, as well as photosensitivity,
      by scalp EEG. One hundred baboons underwent 1-h EEG studies with photic
      stimulation (PS), 49 with previously witnessed seizures and 51 without. The
      animals were classified according to these electroclinical phenotypes: presence
      or absence of interictal epileptic discharges (IEDs), seizures and
      photoparoxysmal or photoconvulsive responses. Effects of age, gender, and species
      on EEG phenotypes were also examined. Six discrete electroclinical phenotypes
      were identified. Generalized IEDs of 2-3, 4-6, and/or 6-7Hz were identified in 67
      baboons. Epileptic seizures were recorded in 40 animals, including myoclonic and
      generalized tonic-clonic seizures. Thirty-three animals were photosensitive.
      Although the prevalence of IEDs and seizures were similar in seizure and
      asymptomatic animals, photosensitivity was more prevalent in the seizure animals
      (p=0.001). P.h. anubis/cynocephalus hybrids were more likely to be photosensitive
      than P.h. anubis (p=0.004). The reliable characterization of distinct epileptic
      phenotypes in this pedigreed colony is critical to the success of future genetic
      analyses to identify genetic factors underlying their epilepsy.

PMID- 15994063
TI  - Is grey literature essential for a better control of publication bias in
      psychiatry? An example from three meta-analyses of schizophrenia.
AB  - Systematic reviews in mental health have become useful tools for health
      professionals in view of the massive amount and heterogeneous nature of
      biomedical information available today. In order to determine the risk of bias in
      the studies evaluated and to avoid bias in generalizing conclusions from the
      reviews it is therefore important to use a very strict methodology in systematic
      reviews. One bias which may affect the generalization of results is publication
      bias, which is determined by the nature and direction of the study results. To
      control or minimize this type of bias, the authors of systematic reviews
      undertake comprehensive searches of medical databases and expand on the findings,
      often undertaking searches of grey literature (material which is not formally
      published). This paper attempts to show the consequences (and risk) of
      generalizing the implications of grey literature in the control of publication
      bias, as was proposed in a recent systematic work. By repeating the analyses for
      the same outcome from three different systematic reviews that included both
      published and grey literature our results showed that confusion between grey
      literature and publication bias may affect the results of a concrete meta
      analysis.

PMID- 15994064
TI  - Dose-related effect of methylphenidate on stopping and changing in children with
      attention-deficit/hyperactivity disorder.
AB  - PURPOSE: The effect of methylphenidate (MPH) on inhibitory control as assessed by
      the stop task in children with attention-deficit/hyperactivity disorder (ADHD)
      could be influenced by task difficulty and may be mediated by attention. SUBJECTS
      AND METHODS: Fifteen children with ADHD performed the stop and the change task
      after placebo, 0.5 and 1.0 mg/kg MPH in a within-subject design. RESULTS: Linear
      trend analysis showed a similar effect of MPH in both tasks and a stronger effect
      for inhibitory control than for attention. Furthermore, a correlation was found
      between blood serum metabolites of norepinephrine and dopamine for attentional
      measures and inhibitory control measures, respectively. DISCUSSION AND
      CONCLUSION: In children with ADHD MPH could act primarily on inhibitory control,
      and is not influenced by task difficulty. Also, attention and inhibitory control
      could have differential pharmacological profiles.

PMID- 15994065
TI  - Antipsychotic agents. Gradually improving treatment from the traditional oral
      neuroleptics to the first atypical depot.
AB  - Relapse is one of the key factors in the long-term outcome of schizophrenia. The
      consequences of relapse are diverse and often unpredictable, and the time to
      recovery and degree of recovery worsen with each successive relapse. There is now
      overwhelming evidence that advances in antipsychotic drug treatment have led to
      significant reductions in the rate of relapse. This review charts the
      developments that have taken place in antipsychotic therapy from the introduction
      of depot formulations, through atypical agents, to the development of the first
      long-acting atypical antipsychotic. Depot formulations of conventional
      antipsychotics were developed in the 1960s and led to fewer relapses and episodes
      of hospitalization, compared with oral equivalents. Meta-analysis has confirmed
      that patients receiving depot antipsychotics experience significantly greater
      global improvement than those receiving the respective oral agents. Conventional
      antipsychotics are, however, associated with a range of potentially serious
      adverse events. The atypical antipsychotics were introduced in the 1990s and have
      significant advantages over conventional agents with regard to positive and
      negative symptoms. There is also evidence that atypical agents can reduce the
      risk of relapse. Importantly, atypical antipsychotics have an improved safety
      profile compared with older agents, particularly with regard to extrapyramidal
      symptoms. One disadvantage of atypical agents has been that they are only
      available in an oral form. The recent development of a long-acting injectable
      formulation of risperidone means that a new treatment option is available to
      physicians.

PMID- 15994066
TI  - Inhibition of amyloid fibril formation of beta-amyloid peptides via the
      amphiphilic surfactants.
AB  - Beta-amyloid peptide (A beta) is the major proteinacious constituent of senile
      plaques in Alzheimer's disease and is believed to be responsible for the
      neurodegeneration process associated with the disease. While the actual size of
      the aggregated species responsible for A beta neurotoxicity and fibrillogenesis
      mechanism(s) remain unknown, retardation of A beta aggregation still holds
      assurance as an effective strategy in reducing A beta-elicited toxicity. The
      research presented here is aimed at examining the inhibitory effect of two
      amphiphilic surfactants, di-C6-PC and di-C7-PC, on the in vitro fibrillogenesis
      process of A beta(1--40) peptides at physiological pH (pH 7.2). Using ThT-induced
      fluorescence, turbidity, Congo red binding, and circular dichroism spectroscopy
      studies, our research demonstrated that the inhibition of A beta(1--40) fibril
      formation was di-C6-PC and di-C7-PC concentration-dependent. The best inhibitory
      action on fibril formation was observed when A beta was incubated with di-C7-PC
      at 100 microM over time. We believe that the outcome from this work will aid in
      the development and/or design of potential inhibitory agents against amyloid
      formation associated with Alzheimer's and other amyloid diseases.

PMID- 15994068
TI  - [Unusual diagnosis of partial left abnormal pulmonary venous return in neonate].
AB  - The authors report on a case of a newborn with partial anomalous pulmonary venous
      return of the lower left pulmonary vein. Diagnosis was performed during the
      introduction of a central venous catheter. The complications of partial anomalous
      pulmonary venous rely principally in the risk of endothelium damage and
      subsequent pulmonary arterial hypertension.

PMID- 15994067
TI  - [Acute leptospirosis in children in Reunion Island: a retrospective review of 16
      cases].
AB  - INTRODUCTION: Leptospirosis is a worldwide zoonosis caused by pathogenic species
      of the genus Leptospira. This infectious disease known with a high incidence in
      Reunion island (French overseas territories in Indian Ocean) is in state of
      endemia especially during rains season. OBJECTIVES: The aim of our work was to
      identify the mains epidemiologic, clinical, biological, and therapeutic features
      of leptospirosis in children. POPULATION AND METHODS: We conducted a
      retrospective analysis of children hospitalized in pediatric unit with the
      diagnosis of leptospirosis from January 2001 to June 2004 in general hospital of
      Saint-Denis. We found out 16 cases (mean age 14 years, range 9-17), mainly boys
      (ratio 7:1). RESULTS: The patient sera reacted most strongly with Leptospira
      interrogans serovars canicola (66%), icterohaemorrhagiae (17%), and sejroe (17%).
      Epidemiologic data indicated contact with contaminated water in most cases (68%).
      Jaundice was present in 43% of the patients, increased transaminase levels in
      56%, renal failure in 50%, meningitis in 25%, ECG abnormalities in 6%,
      respiratory manifestations in 6%, systemic manifestations in 12% and
      thrombocytopenia in 56%. Death rate was zero, but renal failure is likely to
      induce life prognosis. DISCUSSION: The diagnosis' traps are numerous, leading to
      an underestimation and underdiagnosis of the leptospirosis, more over there is a
      lack in specific, reliable, and quick biological test to make the diagnosis. A
      negative polymerase chain reaction analysis (PCR) do not exclude the diagnosis,
      and the microagglutination test (MAT) remains the reference of the undoubtly
      diagnosis of leptospirosis. It appears that it is more often the conjunction of
      epidemiologic data (young boy, swimming or fishing in river, rains season), with
      clinical and biological data that lead to the diagnosis. Diagnosis was not evoked
      at the emergency room in 37% of the patients. CONCLUSION: Leptospirosis should be
      considered face to an influenza like illness especially during rains season.

PMID- 15994069
TI  - [Idiopathic short stature: growth hormone, a therapeutic challenge?].

PMID- 15994070
TI  - Using cognitive task analysis to facilitate the integration of decision support
      systems into the neonatal intensive care unit.
AB  - OBJECTIVE: New medical systems may be rejected by staff because they do not
      integrate with local practice. An expert system, FLORENCE, is being developed to
      help staff in a neonatal intensive care unit (NICU) make decisions about
      ventilator settings when treating babies with respiratory distress syndrome. For
      FLORENCE to succeed it must be clinically useful and acceptable to staff in the
      context of local work practices. The aim of this work was to identify those
      contextual factors that would affect FLORENCE's success. METHODS: A cognitive
      task analysis (CTA) of the NICU was performed. First, work context analysis was
      used to identify how work is performed in the NICU. Second, the critical decision
      method (CDM) was used to analyse how staff make decisions about changing the
      ventilator settings. Third, naturalistic observation of staff's use of the
      ventilator was performed. RESULTS: A. The work context analysis identified the
      NICU's hierarchical communication structure and the importance of numerous types
      of record in communication. B. It also identified important ergonomic and
      practical requirements for designing the displays and positioning the computer.
      C. The CDM interviews suggested instances where problems can arise if the data
      used by FLORENCE, which is automatically read, is not manually verified. D.
      Observation showed that most alarms cleared automatically. When FLORENCE raises
      an alarm, staff will normally be required to intervene and make a clinical
      judgement, even if the ventilator settings are not subsequently changed.
      CONCLUSIONS: FLORENCE must not undermine the NICU's hierarchical communication
      channels (A). The re-design of working practices to incorporate FLORENCE,
      reinforced through its user interface, must ensure that expert help is called on
      when appropriate (A). The procedures adopted with FLORENCE should ensure that the
      data the advice is based upon is valid (C). For example, FLORENCE could prompt
      staff to manually verify the data before implementing any suggested changes.
      FLORENCE's audible alarm should be clearly distinguishable from other NICU alarms
      (D); new procedures should be established to ensure that FLORENCE alarms receive
      attention (D), and false alarms from FLORENCE should be minimised (B, D).
      FLORENCE should always provide the data and reasoning underpinning its advice (A,
      C, D). The methods used in the CTA identified several contextual issues that
      could affect FLORENCE's acceptance. These issues, which extend beyond FLORENCE's
      capability to suggest changes to the ventilator settings, are being addressed in
      the design of the user interface and plans for FLORENCE's subsequent deployment.

PMID- 15994071
TI  - Description logic-based methods for auditing frame-based medical terminological
      systems.
AB  - OBJECTIVE: Medical terminological systems (TSs) play an increasingly important
      role in health care by supporting recording, retrieval and analysis of patient
      information. As the size and complexity of TSs are growing, the need arises for
      means to audit them, i.e. verify and maintain (logical) consistency and
      (semantic) correctness of their contents. This is not only important for the
      management of TSs but also for providing their users with confidence about the
      reliability of their contents. Formal methods have the potential to play an
      important role in the audit of TSs, although there are few empirical studies to
      assess the benefits of using these methods. METHODS AND MATERIAL: In this paper
      we propose a method based on description logics (DLs) for the audit of TSs. This
      method is based on the migration of the medical TS from a frame-based
      representation to a DL-based one. Our method is characterized by a process in
      which initially stringent assumptions are made about concept definitions. The
      assumptions allow the detection of concepts and relations that might comprise a
      source of logical inconsistency. If the assumptions hold then definitions are to
      be altered to eliminate the inconsistency, otherwise the assumptions are revised.
      RESULTS: In order to demonstrate the utility of the approach in a real-world case
      study we audit a TS in the intensive care domain and discuss decisions pertaining
      to building DL-based representations. This case study demonstrates that certain
      types of inconsistencies can indeed be detected by applying the method to a
      medical terminological system. CONCLUSION: The added value of the method
      described in this paper is that it provides a means to evaluate the compliance to
      a number of common modeling principles in a formal manner. The proposed method
      reveals potential modeling inconsistencies, helping to audit and (if possible)
      improve the medical TS. In this way, it contributes to providing confidence in
      the contents of the terminological system.

PMID- 15994073
TI  - Effects of long-acting bronchodilators and placebo on histamine-induced asthma
      symptoms and mild bronchusobstruction.
AB  - STUDY OBJECTIVE: Accurate perception of airway caliber remains an important issue
      in asthma management. The way bronchodilation is perceived is partly related to
      the perception of the efficacy of bronchodilators in relieving complaints. In the
      present study, we compared the effects of salmeterol, formoterol and placebo on
      relief of histamine-induced asthma symptoms and mild bronchusobstruction.
      METHODS: In this randomized controlled, double blind study, 30 asthmatics were
      challenged with histamine until forced expiratory volume in 1s (FEV(1)) fell with
      > or =20%. Subjects received salmeterol, formoterol or placebo after the
      histamine provocation. Pulmonary function (FEV(1)) and asthma symptoms (Asthma
      Symptom Checklist, Borg Dyspnea Scale) were assessed 5 and 20 min later. RESULTS:
      FEV(1) improved significantly more in the salmeterol and formoterol group than in
      the placebo group (P<0.001, P<0.001 and P<0.05, respectively). Salmeterol and
      formoterol were not different with regard to the pulmonary function recovery. No
      significant differences were found between the effects of salmeterol, formoterol
      and placebo on any of the symptom responses at the different time points.
      CONCLUSIONS: We conclude that after a histamine-induced mild bronchusobstruction,
      a similar asthma symptom recovery occurred when inhaling salmeterol, formoterol
      or placebo, despite better recovery of pulmonary function in the active drug
      conditions.

PMID- 15994074
TI  - Semi-rational approaches to engineering enzyme activity: combining the benefits
      of directed evolution and rational design.
AB  - Many research groups successfully rely on whole-gene random mutagenesis and
      recombination approaches for the directed evolution of enzymes. Recent advances
      in enzyme engineering have used a combination of these random methods of directed
      evolution with elements of rational enzyme modification to successfully by-pass
      certain limitations of both directed evolution and rational design. Semi-rational
      approaches that target multiple, specific residues to mutate on the basis of
      prior structural or functional knowledge create 'smart' libraries that are more
      likely to yield positive results. Efficient sampling of mutations likely to
      affect enzyme function has been conducted both experimentally and, on a much
      greater scale, computationally, with remarkable improvements in substrate
      selectivity and specificity and in the de novo design of enzyme activities within
      scaffolds of known structure.

PMID- 15994075
TI  - The prevalence of PIK3CA mutations in gastric and colon cancer.
AB  - A wide variety of tumours show PIK3CA mutations leading to increased
      phosphatidylinositol-3 kinase (PI3K) activity. We have determined the frequency
      of PIK3CA mutations in exons 9 and 20 that has previously been reported as
      mutational hotspot regions in distinct tumour models. One hundred and fifty
      gastrointestinal carcinomas (47 gastric and 103 colorectal) that were
      characterised for MSI status (76 MSI and 74 MSS) by PCR-SSCP sequencing were
      evaluated. We also analysed the association between PIK3CA mutations and KRAS or
      BRAF mutations. PIK3CA mutations in exons 9 and 20 were present in 13.6% and
      10.6% of colorectal and gastric carcinomas, respectively. No differences in
      frequency and type of PIK3CA mutations were found between MSI and MSS colorectal
      carcinomas. All gastric carcinomas with PIK3CA mutations were MSI. The number of
      cases harbouring concomitant PIK3CA and KRAS or BRAF mutations was higher in
      colorectal than in gastric carcinomas (P = 0.016). In colorectal carcinoma,
      PIK3CA mutations occur preferentially together with activating KRAS-BRAF
      mutations (MSI and MSS) while in gastric carcinomas PIK3CA mutations tend to
      occur as isolated events (MSI).

PMID- 15994076
TI  - Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials.
AB  - Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted
      investigational approach for oncology cooperative group and pharmaceutical
      company research programs. However, there remains considerable uncertainty
      regarding the most suitable endpoints for these studies, in part, because short
      term clinical, radiological or biomarker responses have not been fully validated
      as surrogate endpoints that closely relate to long-term breast cancer outcome.
      This shortcoming must be addressed before neoadjuvant endocrine treatment can be
      used as a triage strategy designed to identify patients with endocrine therapy
      "curable" disease. In this summary, information from published studies is used as
      a basis to critique clinical trial designs and to suggest experimental endpoints
      for future validation studies. Three aspects of neoadjuvant endocrine therapy
      designs are considered: the determination of response; the assessment of surgical
      outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024)
      trial that compared letrozole and tamoxifen is used to illustrate a combined
      endpoint analysis that integrates both clinical and biomarker information. In
      addition, the concept of a "cell cycle response" is explored as a simple post
      treatment endpoint based on Ki67 analysis that might have properties similar to
      the pathological complete response endpoint used in neoadjuvant chemotherapy
      trials.

PMID- 15994077
TI  - Manganese and other micronutrient additions to improve yield of Agaricus
      bisporus.
AB  - Previous experiments have demonstrated that significant increases in yield of
      Agaricus bisporus mushrooms were achieved by adding a micronutrient rich
      fertilizer, Micromax, to the compost. This study was performed to determine the
      mineral(s) that are responsible for this yield improvement. An initial experiment
      determined that manganese was the mineral of primary importance; addition of 184
      mg kg-1 Mn increased yield by 10.8%, compared to the control. Subsequent
      experiments demonstrated that the addition of manganese to the compost has a
      stimulatory effect on mushroom yields. Significant yield increases, ranging from
      9.6% to 11.8% (compared to the control), were observed as a result of manganese
      additions varying between 50 and 300 mg kg-1. Also, data from the last set of
      experiments indicated that Micromax additions always resulted in greater yields
      indicating that micronutrients in Micromax, in addition to manganese, may be
      responsible for increasing yields.

PMID- 15994078
TI  - NACHT-LRR proteins (NLRs) in bacterial infection and immunity.
AB  - Eukaryotes have evolved systems to detect bacterial intrusion. Recognition of
      bacteria relies on the sensing of pathogen associated molecular patterns (PAMPs)
      by host pattern recognition molecules (PRMs), which include various families of
      leucine-rich repeat (LRR) bearing proteins in plants and animals. Detection of
      microbes often occurs outside the cell. Recent findings now indicate that mammals
      have also evolved strategies to recognize bacteria inside the cell via members of
      the NACHT-LRR protein family (NLRs). Here, we review the biology of these
      mammalian NLRs and the emerging view of their important, role not solely as PRMs
      but as signalling platforms and regulators of immunity.

PMID- 15994079
TI  - Trigeminal neurinoma associated with Chiari malformation and syringomyelia.
AB  - We report a 36 year-old woman who presented with headaches and hypoesthesia of
      the face. MRI revealed a large dumbbell shaped trigeminal neurinoma extending
      into both the middle and the posterior cranial fossae. In addition, there was a
      Chiari I malformation and syringomyelia. Within two months of tumor resection,
      both the Chiari malformation and the syringomyelia resolved. The association of
      an intracranial space-occupying lesion with Chiari malformation and syringomyelia
      is reviewed.

PMID- 15994080
TI  - Continuous regional cerebral blood flow monitoring in the neurosurgical intensive
      care unit.
AB  - The aim of this study was to examine the intracranial pressure (ICP) and regional
      cerebral blood flow (rCoBF) changes during the acute stage of severe head injury
      and to improve outcome by modifying treatment modalities using real-time ICP and
      rCoBF data. Twenty patients with moderate or severe head injury that were
      monitored in our neurosurgical intensive care unit were included in this study.
      The changes in ICP, rCoBF and the relationship of ICP/rCoBF were observed. In
      patients with high ICP and low rCoBF, mannitol improves the rCoBF and decreases
      the ICP of these patients. When low rCoBF exists, hyperventilation may lead to a
      rapid further decline of rCoBF, however, some hyperemic brains respond well to
      hyperventilation treatment. Triple-H therapy is suitable for those with low rCoBF
      without significantly high ICP, which is an abnormal condition considered to be
      caused by vasospasm.

PMID- 15994081
TI  - Analysis of the risk factors regarding anterior cruciate ligament reconstruction
      using multiple-looped semitendinosus tendon.
AB  - The purpose of this study was to investigate the risk factors regarding anterior
      cruciate ligament (ACL) reconstruction using autogenous semitendinosus tendon by
      subjective evaluation of the patients. We studied 63 patients who had been
      followed for 18 months or longer after surgery. They comprised 31 men and 32
      women aged 15-45 (mean, 25.5) years. The patients were divided into two groups by
      subjective scores. Subjective clinical evaluation was performed using 100 mm
      visual analogue scale (VAS). In the high score group (group H), the VAS score was
      80 mm or higher, and in the low score group (group L), the score was less than 80
      mm. Forty three patients were in group H and 20 patients were in group L. The
      parameters examined were age, gender, sports activity level, preoperative period,
      complicated meniscus injury, articular cartilage status, graft tendon size, joint
      stability, and knee extension muscle strength. There were 26 men and 17 women in
      group H, and 5 men and 15 women in group L. There were significantly more women
      in group L (p<0.01). The mean preoperative period after injury was 23+/-38 months
      in group H, and was 52+/-67 months in group L (p<0.05). The average side-to-side
      differences in anterior laxity were 1.3+/-1.0 mm in group H and 2.2+/-1.6 mm in
      group L (p<0.01). There were no significant differences in other parameters
      between the two groups. In this study the risk factors for poor subjective
      outcome following hamstring ACL surgery was female gender and prolonged delay
      from injury to operation.

PMID- 15994082
TI  - Efficacy of an accelerated recovery protocol for Oxford unicompartmental knee
      arthroplasty--a randomised controlled trial.
AB  - Unicompartmental knee arthroplasty (UKA) is appropriate for one in four patients
      with osteoarthritic knees. This study was performed to compare the safety,
      effectiveness and economic viability of a new accelerated protocol with current
      standard care in a state healthcare system. A single blind RCT design was used.
      Eligible patients were screened for NSAID tolerance, social circumstances and
      geographical location before allocation to an accelerated recovery group (A) or
      standard care group (S). Primary outcome was the Oxford Knee Assessment at 6
      months post operation, compared using independent Mann-Whitney U-tests. A simple
      difference in costs incurred was calculated. The study power was sufficient to
      avoid type 2 errors. Forty-one patients were included. The average stay for Group
      A was 1.5 days. Group S averaged 4.3 days. No significant difference in outcomes
      was found between groups. The new protocol achieved cost savings of 27% and
      significantly reduced hospital bed occupancy. In addition, patient satisfaction
      was assessed as greater with the accelerated discharge than with the routine
      discharge time. The strict inclusion criteria meant that 75% of eligible patients
      were excluded. However, a large percentage of these were due to the distances
      patients lived from the hospital.

PMID- 15994083
TI  - Effect of change in nucleoside structure on the activation and antiviral activity
      of phosphoramidate derivatives.
AB  - Changing the nucleoside group of a series of phosphoramidate derivatives affects
      the enzyme mediated hydrolysis rate of the compounds. d4T and AZT-substituted
      analogs were activated by enzymes such as lipases, esterases, and proteases. On
      the other hand, 3dT-substituted derivatives were comparatively less prone to
      hydrolysis under similar experimental conditions. From the experimental results,
      we propose that the most preferable nucleoside group for enzyme activation is d4T
      rather than AZT or 3dT. Additionally, we also observed that depending on the
      enzymes used the chiral selectivity of the enzymes for the phosphorus center of
      these phosphoramidate derivatives differed, demonstrating the importance of the
      nucleoside structure for this class of compounds.

PMID- 15994084
TI  - 3-N,N-Dimethylamino-3-deoxy lincomycin: a structure-based hybrid between
      lincomycin and the desosamine unit of erythromycin.
AB  - The observation that the desosamine sugar unit in erythromycin and the methyl
      thiolincosaminide portion of lincomycin occupy virtually identical sites on the
      23S rRNA according to X-ray crystallograpaic data, instigated the synthesis of 3
      N,N-dimethylamino-3-deoxy lincomycin as a hybrid structure. The synthesis in
      eight steps from lincomycin, involving a trans-diequatorial opening of an
      intermediate epoxide as the key step, is described.

PMID- 15994085
TI  - Inhibition of the severe acute respiratory syndrome 3CL protease by
      peptidomimetic alpha,beta-unsaturated esters.
AB  - The proteolytic processing of polyproteins by the 3CL protease of severe acute
      respiratory syndrome coronavirus is essential for the viral propagation. A series
      of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres,
      including AG7088, are synthesized and assayed to target the 3CL protease. Though
      AG7088 is inactive (IC50 > 100 microM), the ketomethylene isosteres and
      tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine
      residues show modest inhibitory activity (IC50 = 11-39 microM). The Phe-Phe
      dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the
      enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition
      constant of 0.52 microM is obtained by condensation of the Phe-Phe dipeptide
      alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based
      assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of
      0.18 microM.

PMID- 15994086
TI  - Synthesis, antiproliferative, and vasorelaxing evaluations of coumarin alpha
      methylene-gamma-butyrolactones.
AB  - Certain coumarin alpha-methylene-gamma-butyrolactones were synthesized and
      evaluated for antiproliferative and vasorelaxing activities. These compounds were
      synthesized via alkylation of hydroxycoumarins 2a-f followed by oxidation and the
      Reformatsky-type condensation. The results of this study are as follows (1) for
      the vasorelaxing activity, coumarin-7-yl alpha-methylene-gamma-butyrolactone 6d,
      with an IC50 value of 9.4 microM against pig coronary arterial contraction
      induced by KCl, is a more active vasorelaxant than its coumarin-4-yl counterpart
      6a and its gamma-methyl congener 1. A methyl group substituted at C-4 of the
      coumarin-7-yl moiety reduced the vasorelaxing effect (6d vs 6e) while the 3,4,8
      trimethyl derivative 6f was inactive. (2) For the antiproliferative activity,
      coumarin-4-yl alpha-methylene-gamma-butyrolactone 6a, which exhibited the most
      potent antiproliferative activity on the growth of MCF7, NCI-H460, and SF-268
      with IC50 values of 6.97, 14.68, and 8.36 microM, respectively, is more cytotoxic
      than its coumarin-7-yl counterpart 6d and the 6,7-dimethyl derivative 6b. For the
      coumarin-7-yl derivatives, 6d is more active than its gamma-methyl congener 1,
      indicating that substitution at the gamma-position decreased cytotoxicity.

PMID- 15994087
TI  - Synthesis of long-chain amide analogs of the cannabinoid CB1 receptor antagonist
      N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide (SR141716) with unique binding selectivities and pharmacological
      activities.
AB  - An extended series of alkyl carboxamide analogs of N-(piperidinyl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide
      (SR141716; 5) was synthesized. Each compound was tested for its ability to
      displace the prototypical cannabinoid ligands ([3H]CP-55,940, [3H]2;
      [3H]SR141716, [3H]5; and [3H]WIN55212-2, [3H]3), and selected compounds were
      further characterized by determining their ability to affect guanosine 5'
      triphosphate (GTP)-gamma-[35S] binding and their effects in the mouse vas
      deferens assay. This systematic evaluation has resulted in the discovery of novel
      compounds with unique binding properties at the central cannabinoid receptor
      (CB1) and distinctive pharmacological activities in CB1 receptor tissue
      preparations. Specifically, compounds with nanomolar affinity which are able to
      fully displace [3H]5 and [3H]2, but unable to displace [3H]3 at similar
      concentrations, have been synthesized. This selectivity in ligand displacement is
      unprecedented, in that previously, compounds in every structural class of
      cannabinoid ligands had always been shown to displace each of these radioligands
      in a competitive fashion. Furthermore, the selectivity of these compounds appears
      to impart unique pharmacological properties when tested in a mouse vas deferens
      assay for CB1 receptor antagonism.

PMID- 15994088
TI  - 9-Oxime-3-ketolides: modification at the C-11,12-diol moiety and antibacterial
      activities against key respiratory pathogens.
AB  - In the search for new types of ketolide antibiotics active against key
      respiratory pathogens including erythromycin-resistant strains, we conducted an
      extensive study on the modification at the C-11,12-diol moiety of 9-oxime-3
      ketolide derivatives. Among the derivatives prepared, compound 6 with carbonate
      at the C-11,12 position was found to have potent antibacterial activities against
      erythromycin-resistant Staphylococcus aureus as well as other erythromycin
      susceptible strains.

PMID- 15994089
TI  - In vivo prompt gamma neutron activation analysis of cadmium in the kidney and
      liver.
AB  - An existing McMaster University in vivo prompt gamma neutron activation analysis
      system has been improved in order to reduce the cadmium detection limit in the
      kidney and liver. The detection limit for the kidney was found to be 1.7 mg, a
      greater than factor of 2 improvement over the previous results obtained at
      McMaster. The liver detection limit was determined to be 3.3 ppm. The
      corresponding skin dose for these measurements was only 0.5 mSv. The effect of
      kidney position on the detection limit also was examined. Figures of merit were
      calculated in order to compare the performance of the current system to others.

PMID- 15994090
TI  - Energy behavior of neutrons around axi-symmetric sealed-off neutron generating
      tubes.
AB  - The aim of this paper is to contribute to analytical characterization of the
      spatial dependency of the mean energy of fast neutrons produced in non-dispersive
      media by sealed-off neutron generating tubes (NGT) having axial symmetry.
      Neutrons are generated in most of NGT by accelerating a mixture of hydrogen
      isotope ions (deuterons and tritons) onto plane self-targets. Deuterons and
      tritons are implanted in the mentioned targets and become target nuclei for the
      subsequent incoming ions. d-T, t-D and d-D fast neutrons are generated.
      Analytical expressions for the neutron mean energy in these three cases are
      deduced, taking into account the exothermic character of the reactions. Due
      consideration is paid to collision kinetics, depending upon mass and kinetic
      energy of particles involved in the nuclear reaction, nuclear reaction energy,
      etc.

PMID- 15994091
TI  - Gamma-ray density and thickness gauges using ultra-low activity radioisotope
      sourcesfillin.
AB  - Most commercial nuclear density gauges use either (137)Cs or (60)Co sources of
      activity between about 185 and 1850 MBq (5 and 50 mCi). In the current work,
      density and thickness gauges that use ultra-low activity gamma-ray sources that
      are exempt from licensing requirements have been investigated. Results are
      reported on gauges that use a 1 MBq (22)Na source for determining slurry density
      in the CSIRO UltraPS slurry particle size analyser and for determining belt
      loading in the CSIRO on-conveyor belt microwave moisture gauge.

PMID- 15994092
TI  - GATA3 haploinsufficiency causes a rapid deterioration of distortion product
      otoacoustic emissions (DPOAEs) in mice.
AB  - Human HDR (hypoparathyroidism, deafness and renal dysplasia)-syndrome is caused
      by haploinsufficiency of zinc-finger transcription factor GATA3. The hearing loss
      due to GATA3 haploinsufficiency has been shown to be peripheral in origin, but it
      is unclear to what extent potential aberrations in the outer hair cells (OHCs)
      contribute to this disorder. To further elucidate the pathophysiological
      mechanism underlying the hearing defect in HDR-syndrome, we investigated the OHCs
      in heterozygous Gata3-knockout mice at both the functional and morphological
      level. While the signal-to-noise ratios of distortion product otoacoustic
      emissions (DPOAE) in wild type mice did not change significantly during the first
      half-year of live, those in the heterozygous Gata3 mice decreased dramatically.
      In addition, both light microscopic and transmission electron microscopic
      analyses showed that the number of OHCs containing vacuoles was increased in the
      mutants. Together, these findings indicate that outer hair cell malfunctioning
      plays a major role in the hearing loss in HDR-syndrome.

PMID- 15994093
TI  - Prenatal hypoxia-induced adaptation and neuroprotection that is inducible nitric
      oxide synthase-dependent.
AB  - The incidence of perinatal stroke is approximately 0.025%. About two thirds of
      these patients develop long-lasting neurological deficits. Preconditioning
      induced neuroprotection, a phenomenon in which application of a stimulus induces
      brain ischemic tolerance, is investigated to improve outcome after a perinatal
      stroke. We applied prenatal hypoxia to fetuses by exposing 22-day pregnant mother
      rats to 15% oxygen for 30 min and subjected newborns with or without this
      prenatal hypoxia to brain ischemia 48 h later. Newborns with the prenatal hypoxia
      had a lower mortality rate, less brain tissue and neuronal loss and fewer active
      caspase 3 (an indicator for cell apoptosis) positive brain cells than newborns
      with the brain ischemia only. This neuroprotection was abolished by an inhibitor
      of inducible nitric oxide synthase (iNOS). The expression of iNOS proteins but
      not endothelial and neuronal NOS proteins was increased by the prenatal hypoxia.
      Thus, the prenatal hypoxia-induced neuroprotection may be iNOS-dependent.

PMID- 15994094
TI  - Typical echocardiographic appearance of a ruptured sinus of Valsalva aneurysm in
      a previously healthy 30-year-old man.

PMID- 15994095
TI  - Mutant huntingtin represses CBP, but not p300, by binding and protein
      degradation.
AB  - Huntington's disease can be used as a model to study neurodegenerative disorders
      caused by aggregation-prone proteins. It has been proposed that the entrapment of
      transcription factors in aggregates plays an important role in pathogenesis. We
      now report that the transcriptional activity of CBP is already repressed in the
      early time points by soluble mutant huntingtin, whereas the histone acetylase
      activity of CBP/p300 is gradually diminished over time. Mutant huntingtin bound
      much stronger to CBP than normal huntingtin, possibly contributing to repression.
      Especially at the later time points, CBP protein level was gradually reduced via
      the proteasome pathway. In sharp contrast, p300 was unaffected by mutant
      huntingtin. This selective degradation of CBP was absent in spinocerebellar
      ataxia 3. Thus, mutant huntingtin specifically affects CBP and not p300 both at
      the early and later time points, via multiple mechanisms. In addition to the
      reduction of CBP, also the altered ratio of these closely related histone
      acetyltransferases may affect chromatin structure and transcription and thus
      contribute to neurodegeneration.

PMID- 15994096
TI  - Risk of selected cardiovascular diseases and posttraumatic stress disorder among
      former World War II prisoners of war.
AB  - PURPOSE: American World War II (WWII) prisoners of war (POWs) suffered both
      mental and physical deprivation while interned. The long-term health consequences
      of the internment were studied for an increased risk of cardiovascular diseases
      and posttraumatic stress disorder (PTSD). METHODS: This study evaluated
      healthcare utilization data for 10 years (1991-2000) from Veterans Affairs (VA)
      and non-VA healthcare providers for 19,442 former WWII POWs and 9728 non-POW
      controls. The risk of diseases was approximated by odds ratios adjusted for race
      and age. RESULTS: Collectively, former POWs had statistically significant
      increased risk of PTSD, and those POWs with PTSD also had statistically
      significant increased risks of cardiovascular diseases including hypertension and
      chronic ischemic heart disease when compared to both non-POWs and POWs without
      PTSD. CONCLUSIONS: Among former WWII POWs, risk of cardiovascular disease is
      related to having PTSD.

PMID- 15994097
TI  - A cohort study of injuries in migrant farm worker families in South Texas.
AB  - PURPOSE: This cohort study estimated the frequency of and risk factors for work
      injuries among migrant farmworker families over a two-year period. METHODS: The
      cohort consisted of 267 families. Bilingual interviewers asked mothers to respond
      for their family soliciting demographic, psychosocial, employment, and work
      related injury information. Cox regression was used to examine risk factors for
      first injury events. RESULTS: Of the 267 families, nearly 60% migrated and 96% of
      these completed the follow-up interviews. These families represented about 310
      individuals each year who had participated in farmwork on average 6 days a week,
      10 hours a day, for 2.7 months in the past year. Twenty-five work-related
      injuries were reported with an overall rate of 12.5/100 FTE (95% C.I., 8.6-19.0).
      Working for a contractor increased the hazard ratio, and use of car seat belts
      and working for more than one employer during the season decreased it.
      CONCLUSIONS: If person-time at risk for injuries is taken into account the
      reported injuries are substantial. Because the injuries were quite diverse,
      specific interventions may have to focus on improved working conditions (physical
      and economic), ergonomic modifications, and enhanced enforcement of existing
      regulations.

PMID- 15994098
TI  - Social contracts and precautions activate different neurological systems: an fMRI
      investigation of deontic reasoning.
AB  - We conducted an event-related, functional MRI investigation of 12 male's and 12
      female's reasoning about conditional deontic rules, rules regulating people's
      behavior. We employed two different types of rules: social contracts and
      nonsocial, precautionary rules. Although the rules and the demands of the task
      were matched in terms of their logical structure, reasoning about social
      contracts and precautions activated a different constellation of neurological
      structures. The regions differentially activated by social contracts included
      dorsomedial PFC (BA 6/8), bilateral ventrolateral PFC (BA 47), the left angular
      gyrus (BA 39), and left orbitofrontal cortex (BA 10). The regions differentially
      activated by precautions included bilateral insula, the left lentiform nucleus,
      posterior cingulate (BA 29/31), anterior cingulate (BA 24) and right postcentral
      gyrus (BA 3). Collectively, reasoning about prescriptive rules activated the
      dorsomedial PFC (BA 6/8). The results reinforce the view that human reasoning is
      not a unified phenomenon, but is content-sensitive.

PMID- 15994099
TI  - Phosphatidylinositol-4-phosphate 5-kinase gamma is associated with cell-cell
      junction in A431 epithelial cells.
AB  - Cell to cell contact in epithelial cells is crucial for tissue integrity and is
      maintained by junctional complexes, such as the adherens junction (AJ). Actin
      polymerization has been shown to be important for AJ formation; however, the
      molecular mechanisms have yet to be clarified. It has been shown that increased
      phosphatidylinositol-4,5-bisphosphate (PIP2) induces actin polymerization. It is
      thus of interest to know more about the production of PIP2 during cell-cell
      adhesion formation in epithelial cells. The distribution of phosphatidylinositol
      4-phosphate 5-kinase gamma635 (PIP5Kgamma635), an isoform of the PIP2
      synthesizing enzymes, was examined in epithelial cell line A431. It was found
      that, in non-contact cells, PIP5Kgamma635 was not concentrated at the plasma
      membrane. However, in cells that were in contact, PIP5Kgamma635 localized to the
      intercellular contact sites and colocalized with E-cadherin and beta-catenin, two
      components of AJ, and with polymerized actin, but did not colocalize with focal
      adhesion, integrin-mediated cell-substratum complex. Decreasing calcium ion
      concentration induced both disruption of intercellular adhesion and the
      dissociation of both PIP5Kgamma635 and actin from the contact site. These results
      suggest that PIP5K has an important role in actin polymerization in epithelial
      cell-cell adhesion.

PMID- 15994100
TI  - Sleep-related erections: clinical perspectives and neural mechanisms.
AB  - Involuntary sleep-related erections (SREs) occur naturally during REM sleep in
      sexually potent men and other mammals. The regularity of their pattern and non
      volitional nature made SREs useful clinically for differentiating psychogenic and
      organic erectile dysfunction (ED) in candidates for surgical intervention.
      Normative data available for different age groups added to the attractiveness of
      SRE measurement for clinical decision-making. Clinical SRE testing is less
      commonly applied today with the advent of minimally invasive medical therapies
      for ED. Nonetheless, as an objective measure of erectile function, SRE recording
      for research provides a precise technique for examining the mechanisms of
      erection and is still conducted to resolve legal disputes. SRE alterations
      provoked hormonally and pharmacologically are discussed. Different SRE patterns
      are associated with comorbid factors and some of these are illustrated,
      described, or both. Recording techniques developed for rats have proved extremely
      valuable for furthering our understanding of brain centers mediating erectile
      response. Data from lesion and stimulation studies are examined in the present
      review, moving us a step closer to understanding the underpinnings of erectile
      function.

PMID- 15994101
TI  - Ciprofloxacin and norfloxacin pharmacokinetics and prostatic fluid penetration in
      dogs after multiple oral dosing.
AB  - The aims of this study were to assess the pharmacokinetics and
      pharmacokinetic/pharmacodynamic (PK/PD) indices predictive of clinical outcome of
      ciprofloxacin (CIP) and norfloxacin (NOR) after multiple oral dosing, and to
      investigate their penetration into prostatic fluid in dogs. Eight dogs received
      seven oral doses b.i.d. of NOR (20 mg/kg) and CIP (15 mg/kg). Drug concentrations
      were determined in blood and in two prostatic fluid samples. Prostatic fluid
      concentrations were lower than plasma concentrations for both drugs. No
      statistically significant differences were determined between the pharmacokinetic
      parameters calculated after the first and seventh doses for either CIP or NOR.
      The PK/PD indices were found to be useful for predicting bacteriological outcome
      for fluoroquinolones (area under the disposition curve/minimum inhibitory
      concentration [MIC] and peak plasma concentration/MIC) and indicate that with
      this dose regimen CIP presents a more favourable disposition than NOR for
      successful clinical outcome.

PMID- 15994102
TI  - Laminectomy membrane formation in dogs: is the answer still elusive?

PMID- 15994103
TI  - Identification of avian strains of Pasteurella multocida in India by conventional
      and PCR assays.
AB  - The prevalence of capsular and somatic serotypes were studied among 123
      Pasteurella multocida strains isolated from chickens (n=94), ducks (22), quails
      (4), turkeys (2) and geese (1) from different geographical regions of India. All
      strains exhibited similar cultural and morphological characteristics. Ninety-two
      of the isolates belonged to serotype A:1, the most prevalent serotype, with
      serotypes A:3, A:1,3, D:3 and F:3 having two isolates each. Only one isolate was
      positive for serotypes A:4 and D:1. Twenty isolates were untyped. A multiplex
      capsular PCR assay generated amplicons of sizes approximately 460, approximately
      1044, approximately 657 and approximately 854 bp in 106 isolates identified as
      capsular serotype-A, 15 in serotype D and two in serotype F. Capsular types B and
      E were not detected in any of the avian isolates studied. The present findings
      suggest that a multiplex capsular PCR assay may be suitable for the rapid initial
      identification serotypes P. multocida during epidemiological studies of fowl
      cholera.

PMID- 15994104
TI  - Prevalence of feline infectious peritonitis in specific cat breeds.
AB  - Although known that purebreed cats are more likely to develop feline infectious
      peritonitis (FIP), previous studies have not examined the prevalence of disease
      in individual breeds. All cats diagnosed with FIP at a veterinary teaching
      hospital over a 16-year period were identified. Breed, sex and reproductive
      status of affected cats were compared to the general cat population and to mixed
      breed cats evaluated during the same period. As with previous studies sexually
      intact cats and purebreed cats were significantly more likely to be diagnosed
      with FIP; males and young cats also had a higher prevalence of disease.
      Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes had a significantly
      higher risk, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues
      and Siamese cats were not at increased risk for development of FIP. Although
      additional factors doubtlessly influence the relative prevalence of FIP, this
      study provides additional guidance when prioritizing differentials in ill
      purebreed cats.

PMID- 15994105
TI  - Hypervitaminosis A in the cat: a case report and review of the literature.
AB  - A case of hypervitaminosis A with secondary entrapment and compression of the
      left brachial plexus nerve roots is described. A 9-year-old male castrated
      domestic shorthair, fed a home-made diet based on raw pork liver, was submitted
      for examination for a left forelimb lameness that evolved to paralysis over a 2
      month period. Clinical examination revealed a flaccid paralysis and atrophy of
      all left forelimb muscles. An ipsilateral Horner's syndrome was also noted.
      Radiological examination of the cervical and thoracic spine showed massive new
      bone formation at the ventral aspect of the second cervical to sixth thoracic
      vertebra. The diagnosis of hypervitaminosis A was made, based on the clinical and
      radiographic findings, as well as the determination of serum vitamin A
      concentration, which was 630 microg/dl, three times above the upper normal limit
      for this species. Despite the unfavourable initial prognosis, the cat
      progressively regained function of the affected limb approximately 6 months after
      the diet was changed to a commercial canned food.

PMID- 15994106
TI  - Blood typing in Saimiri sciureus monkeys: influence of anti-red blood cell
      alloantibodies on Plasmodium falciparum parasitaemia in vivo.
AB  - The Saimiri sciureus monkey is a well-established host for experimental studies
      with human malaria parasites. During the course of iterative inoculations with
      Plasmodium falciparum parasitised red blood cells (RBC), anti-RBC alloantibodies
      were detected in the sera of two of eight Saimiri monkeys. These anti-RBC
      antibodies were further used to investigate RBC phenotypes in 35 colony-reared
      Saimiri monkeys by flow cytometry. Three RBC phenotypes (named I-III) were
      observed. Their distribution was I (86%), II (11%) and III (3%). Using the Palo
      Alto FUP-2 strain, a variant P. falciparum line insensitive to hyperimmune serum
      and the passive transfer of anti-RBC alloantibodies, a dramatic drop in parasite
      growth was documented in an incompatible monkey.

PMID- 15994107
TI  - Cerebral malaria is frequently associated with latent parasitemia among the semi
      immune population of eastern Sudan.
AB  - The accurate diagnosis of malaria starts with clinical suspicion, confirmed by
      reliable laboratory results. A hospital-based study, described here, was carried
      out in a malaria mesoendemic area in eastern Sudan, where the inhabitants are
      semi-immune to malaria, and the fever threshold of parasitemia is not above the
      detection level of microscopy. Thus, we hypothesized that patients with symptoms
      highly suggestive of cerebral malaria (CM), but aparasitemic by microscopy, may
      have submicroscopic parasitemia. Patients in our malaria clinic were screened by
      microscopy, and 120 individuals were selected for the study, including febrile
      patients with and without microscopically detectable parasitemia, and apparently
      healthy individuals. In the two former groups there were patients with severe
      anemia and deep coma. Polymerase chain reaction (PCR) for parasite detection and
      ELISA tests for measuring serum antibody levels were carried out on all blood
      samples. A majority of the febrile patients who were parasite negative by
      microscopy showed the presence of a Plasmodium falciparum infection by PCR. The
      occurrence of P. falciparum infection with parasitemia below the detection level
      of microscopy was recognized more often in patients with CM symptoms than in
      those with severe malarial anemia (SMA), and in older rather than younger
      patients. Patients clinically suspected (CS) of having CM ((CS)CM) mostly were
      infected with a single clone, and a large proportion of them acquired antibodies
      (Abs) against merozoite surface protein (MSP) antigens (Ags). The therapeutic
      response to quinine treatment was comparable between patients with (CS)CM and CM.
      In conclusion, uniquely in this setting, CM can be associated with sub-patent
      parasitemia; thus, a diagnostic tool more sensitive than microscopy is needed.

PMID- 15994108
TI  - In vivo efficiency of targeted norfloxacin against persistent, isoniazid
      insensitive, Mycobacterium bovis BCG present in the physiologically hypoxic mouse
      liver.
AB  - Persistence of Mycobacterium tuberculosis is a hypoxia-inducible state in which
      the bacteria are phenotypically insensitive to currently available
      antituberculous drugs. In humans, persistent M. tuberculosis is found in
      granulomatous lesions, either inside macrophages or in necrotic tissue, where the
      partial oxygen pressure (pO(2)) is very low. Persistent bacteria can remain
      silent for decades before overt tuberculosis develops. Due to insensitivity to
      classical drugs, M. tuberculosis persistence prevents rapid and definitive
      clearance of bacteria. Consequently, therapeutic molecules are required that are
      both active against persistent bacilli and able to reach their intramacrophagic
      location. In contrast to its native form, norfloxacin is active in vivo against
      Mycobacterium bovis BCG present in the lungs when temporarily linked to a
      macromolecular carrier targeted to macrophages. To study the efficiency of this
      macromolecular prodrug targeted to persistent mycobacteria confined inside
      macrophages, we established a short-term in vivo model based on the physiological
      pO(2) differences between lungs, spleen and liver. Whereas lungs and spleen are
      well oxygenated, the liver has a low pO(2) due to its portal irrigation.
      Therefore, studying mycobacteria in the liver yields information about in vivo
      persistent bacilli exposed to low pO(2). To our knowledge, no similar short-term
      in vivo model has been published to date. Using this model, we demonstrated the
      insensitivity to isoniazid of M. bovis BCG present in hypoxic sites, and showed
      that norfloxacin given as a mannosylated macrophage-targeted prodrug was able to
      kill these isoniazid-insensitive mycobacteria. This demonstrates that
      intracellular persistent mycobacteria are amenable to antibiotic treatment.

PMID- 15994109
TI  - Pulsed-field gel electrophoresis analysis of Bordetella pertussis populations in
      various European countries with different vaccine policies.
AB  - The increasing incidence of pertussis in a number of countries, despite good
      vaccination coverage, is a cause for concern. We used pulsed-field gel
      electrophoresis (PFGE) typing to examine the genetic diversity of 101 clinical
      isolates of Bordetella pertussis, recovered during 1999-2001, and circulating in
      five different European countries to evaluate temporal and geographical
      distribution. This DNA fingerprinting approach seems to be a more discriminative
      epidemiological tool than sequencing of individual genes. Despite differences in
      vaccination policies in the five countries, these European isolates were found to
      be very similar and fell into the same major PFGE profile groups, with a
      predominance of one profile group. There was no evidence of geographic
      clustering, except that one new profile subgroup was predominantly found in one
      country. This study provides a baseline for continued surveillance of the B.
      pertussis population in Europe.

PMID- 15994110
TI  - Systemic sclerosis and gastric MALT lymphoma.
AB  - CASE-REPORT: A 76-year-old woman was admitted for evaluation of esophagitis
      complicating limited cutaneous systemic sclerosis. Endoscopy showed persistent
      grade III esophagitis and an erythematous antral lesion found upon biopsy to be a
      lymphoma of mucosa-associated lymphoid tissue (MALT). Tests were positive for
      Helicobacter pylori. Moderate mucosal infiltration by endoscopic ultrasonography
      was the only finding from staging investigations. Six months after treatment to
      eradicate H. pylori, a repeat endoscopy showed no evidence of the lesion.
      DISCUSSION: MALT lymphomas are usually confined to the gastric wall. Gastric MALT
      lymphomas have a well-established association with H. pylori infection. The
      clinical manifestations are nonspecific. Endoscopy usually shows a focus of
      erythema or, less often, erosion. The diagnosis rests on histological examination
      of a biopsy, which shows infiltration by monoclonal cells whose immunophenotype
      is characteristic of marginal-zone B cells. Eradication of H. pylori is the
      mainstay of treatment.

PMID- 15994111
TI  - Test-retest repeatability of self-reported environmental exposures in Parkinson's
      disease cases and healthy controls.
AB  - There is substantial disagreement among published epidemiological studies
      regarding environmental risk factors for Parkinson's disease (PD). Differences in
      the quality of measurement of environmental exposures may contribute to this
      variation. The current study examined the test-retest repeatability of self
      report data on risk factors for PD obtained from a series of 32 PD cases
      recruited from neurology clinics and 29 healthy sex-, age- and residential suburb
      matched controls. Exposure data were collected in face-to-face interviews using a
      structured questionnaire derived from previous epidemiological studies. High
      repeatability was demonstrated for 'lifestyle' exposures, such as smoking and
      coffee/tea consumption (kappas 0.70-1.00). Environmental exposures that involved
      some action by the person, such as pesticide application and use of solvents and
      metals, also showed high repeatability (kappas>0.78). Lower repeatability was
      seen for rural residency and bore water consumption (kappa 0.39-0.74). In
      general, we found that case and control participants provided similar rates of
      incongruent and missing responses for categorical and continuous occupational,
      domestic, lifestyle and medical exposures.

PMID- 15994112
TI  - The long-lasting improvement of sexual dysfunction in patients with advanced,
      fluctuating Parkinson's disease induced by pergolide: evidence from the results
      of an open, prospective, one-year trial.
AB  - Fourteen male patients suffering from Parkinson's disease, each of whom had been
      treated with L-DOPA, and in whom additional treatment with oral dopamine agonist
      (DA) was needed, were followed for a period of one year. Pergolide mesylate
      (Permax) was given to each patient, and titrated to a total daily dose of 3 mg.
      All of the patients were taking L-DOPA. The assessments performed before the
      start of pergolide treatment consisted of neurological examination, unified
      Parkinson's disease rating scale (UPDRS) III and IV subscales scoring, mini
      mental state examination (MMSE) scoring, the neuropsychological examination
      including Zung scale scoring, biochemical and hematological examinations
      including prolactine serum levels; and a sexological examination during which the
      patients filled-in the international index of erectile function (IIEF)
      questionnaire. These examinations were repeated during the control assessments at
      months 1, 3, 6 and 12. ANOVA, non-parametric Friedmann's ANOVA and Tukey post hoc
      tests were used for the statistical analysis. There were statistically
      significant differences between the values of UPDRS III motor subscale and all
      subscales of IIEF when months 0 and 1 were compared with the results obtained at
      months 3, 6 and 12. Pergolide mesylate, when added to L-DOPA, significantly
      improved all sexual functions in younger male Parkinsonian patients who were
      still interested in sexual activities. The treatment with pergolide in these
      cases might be more beneficial than with short-acting PDE-5 inhibitor
      sildenafile. Nevertheless, the relationship between pergolide treatment and
      incidence of restrictive valvular heart disease must be considered.

PMID- 15994113
TI  - Electroconvulsive therapy for depression in a Parkinson's disease patient with
      bilateral subthalamic nucleus deep brain stimulators.
AB  - We report a patient with advanced Parkinson's disease (PD) who developed a
      recurrence of major depression with psychotic features after bilateral
      subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Electroconvulsive
      therapy (ECT) dramatically improved the depression without shifting electrode
      position or damaging the DBS hardware. This case suggests that ECT can be a safe
      and effective option for severe depression in PD patients treated with STN DBS.

PMID- 15994114
TI  - Inter-examiner reliability of passive assessment of intervertebral motion in the
      cervical and lumbar spine: a systematic review.
AB  - A systematic review was conducted to determine inter-examiner reliability of
      passive assessment of segmental intervertebral motion in the cervical and lumbar
      spine as well as to explore sources of heterogeneity. Passive assessment of
      motion is used to decide on treatments for neck and low-back pain patients. Inter
      examiner reliability has been a matter of debate, resulting in questions about
      professional credibility and accountability. A structured search for relevant
      studies in MEDLINE and CINAHL was followed by extensive reference tracing and
      hand searching. Studies presenting estimates of reliability for individual motion
      segments were included. No language restrictions were imposed. Study quality was
      assessed using criteria derived from the Standards for Reporting of Diagnostic
      Accuracy (STARD) statement and a quality assessment tool for studies of
      diagnostic accuracy included in systematic reviews (QUADAS). Study selection,
      quality assessment, and data extraction were performed by two reviewers
      independently. Qualitative analyses and additional subgroup analyses were
      conducted. Nineteen studies were included. Two studies satisfied criteria for
      external and internal validity, of which one found fair to moderate reliability.
      Assessment of motion segments C1-C2 and C2-C3 almost consistently reached at
      least fair reliability. Overall, inter-examiner reliability was poor to fair.
      However, most studies were found to be of poor methodological quality. We propose
      explicit recommendations for the conduct and reporting of future research.

PMID- 15994115
TI  - Laser Raman and infrared spectral studies of dl-phenylalaninium nitrate.
AB  - The vibrational band assignments of dl-phenylalaninium nitrate in the crystalline
      state are made by recording the infrared and Raman spectra at room temperature.
      The presence of carbonyl (C=O) group has been identified. The prominent marker
      bands of the aromatic amino acid phenylalanine have been observed and the various
      modes of vibration have been assigned. The extensive intermolecular hydrogen
      bonding in the crystal has been identified by the shifting of bands due to the
      stretching and bending modes of the various functional groups. The nitrate group
      forms the anion. The stretching and bending wave numbers of the NO(3)(-) anion
      are different from those observed for free ion state and the degenerating mode of
      vibrations is also lifted. These reveal that the crystalline field has influenced
      the symmetry of the nitrate ion.

PMID- 15994116
TI  - l-Cysteine: Neutron spectroscopy, Raman, IR and ab initio study.
AB  - Inelastic incoherent neutron scattering (IINS) spectra were obtained at 10K for
      normal and deuterated l-cysteine. Raman and infrared spectra were also recorded.
      Geometry of l-cysteine molecule was optimized for the zwitterion form using ab
      initio HF/6-31G* level. The theoretical frequencies of normal and d(4)-l-cysteine
      were compared with INS, Raman and IR spectra. Normal coordinate analysis and band
      assignments based on ab initio calculations and experimental data are presented.

PMID- 15994117
TI  - Diagnosis of human metapneumovirus and rhinovirus in patients with respiratory
      tract infections by an internally controlled multiplex real-time RNA PCR.
AB  - BACKGROUND: Adequate laboratory diagnosis of human rhinoviruses (hRV) and human
      metapneumoviruses (h MPV) requires molecular methods as viral culture lacks
      sensitivity. However, setting up individual PCRs for all respiratory viruses is
      not practical so preferentially multiplex PCRs are used. OBJECTIVES: To develop
      for routine diagnosis a rapid real-time PCR assay for detection of hRV and h MPV
      including an internal control in a single tube multiplex reaction using probes
      carrying different fluorophores to discriminate targets. STUDY DESIGN: The
      multiplex real-time RNA PCR was optimized to include the internal control virus
      and a total of 358 respiratory samples from 239 patients taken over a one-year
      period were analyzed by the multiplex assay. RESULTS: The multiplex assay with co
      amplification of the internal control was as sensitive and specific as the
      individual assays. Application of this assay on clinical samples from 239
      patients in a one-year period resulted in an incidence of hRV and h MPV of 41/239
      (17.1%) and 6/239 (2.5%), respectively. Inhibition, defined as poor internal
      control amplification, was detected in 8 (2.2%) samples. Culture was performed on
      these samples and only four hRV were detected. CONCLUSIONS: This real-time PCR
      method enables sensitive diagnosis of these two respiratory pathogens with the
      potential to expand the assay as part of a full molecular respiratory viral
      screen.

PMID- 15994118
TI  - Transfusion of multi-factors activated immune cells as a novel treatment for
      patients with chronic hepatitis B.
AB  - BACKGROUND AND OBJECTIVES: Host-virus interactions play a central role in
      determining the prognosis of hepatitis B virus infection. Multi-factors activated
      immune cells (MAICs) are autologous peripheral blood mononuclear cells activated
      with anti-CD3 monoclonal antibody, interleukin-2 and interferon-gamma. The
      present pilot clinical trial was designed to determine whether adoptively
      transferred MAICs inhibit the replication of hepatitis B virus and is safe for
      patients. STUDY DESIGN: Fourteen patients with chronic hepatitis B were enrolled
      in the study. A total of (1.5-4.0)x10(9) peripheral blood mononuclear cells were
      isolated from each patient and activated by anti-CD3 monoclonal antibody,
      interleukin-2 and interferon-gamma in vitro for 10 days to produce MAICs. Cell
      phenotypes and levels of cytokine secretion were determined during cell culture.
      Patients were followed up for 1 year after the transfusion of MAICs. RESULTS:
      After 10 days of culture, peripheral blood mononuclear cells were expanded to a
      mean fold of 4.68+/-1.78 and activated effectively, as demonstrated by CD25
      expression and cytokine secretion. Cell activation peaked on day 4. All patients
      accepted the MAICs transfusion with some slight adverse events, and fulminant
      hepatitis and bilirubinemia were not observed. Significant HBV inhibition was
      observed in 8 out of 14 patients, in which 5 patients achieved complete response
      (defined as that serum HBV DNA levels below the detection limit, occurrence of
      HBeAg seroconversion and normalization of ALT were observed together after MAICs
      transfusion and kept for at least 6 months) and 3 patients achieved partial
      response (defined as that serum HBV DNA levels below the detection limit,
      occurrence of HBeAg disappearance and normalization of ALT were observed together
      in 6 months after MAICs transfusion, but kept for less than 6 months).
      CONCLUSION: These findings strongly suggest that MAICs transfusion, which
      effectively inhibits the replication of hepatitis B virus, is safe for patients.

PMID- 15994119
TI  - Cholic acid as key regulator of cholesterol synthesis, intestinal absorption and
      hepatic storage in mice.
AB  - To study the effects of cholic acid (CA) feeding on hepatic cholesterol
      metabolism, male sterol 12alpha-hydroxylase (CYP8B1) knockout (-/-) mice and
      wildtype controls (+/+) were fed either a control diet or the same diet
      supplemented with CA (0.1% or 0.5% w/w) or cholesterol (1% w/w). During feeding
      of the control diet, cholesterol synthesis was increased in CYP8B1-/- compared to
      +/+ mice. Both cholesterol and CA feeding down regulated mRNA expression of
      cholesterogenic genes and hepatic de novo cholesterol synthesis as also reflected
      by a concomitant decrease in the nuclear factor SREBP-2 precursor protein and
      increased hepatic free cholesterol levels. Mice with an intact CYP8B1 gene
      (CYP8B1+/+ and C57Bl/6 mice) accumulated higher concentrations of cholesteryl
      esters (24- and 25-fold, respectively) in their livers compared to CYP8B1-/- mice
      (8-fold). Feeding of CA increased intestinal cholesterol absorption in CYP8B1+/+
      mice by 23% and in CYP8B1-/- mice by 50%. While plasma cholesterol did not differ
      between CYP8B1+/+ and -/- mice under control conditions and cholesterol feeding a
      decrease was seen in CYP8B1-/- but not CYP8B1+/+ mice fed CA. This study
      indicates that CA is an important determinant for intestinal cholesterol
      absorption and that the levels of the transcription factor SREBP-2 in the liver
      are dependent upon the combined effect of CA on intestinal cholesterol absorption
      and CYP7A1. The possibility is discussed that inhibition of CYP8B1 and thus CA
      synthesis may be beneficial for the treatment of hyperlipidemic disorders.

PMID- 15994120
TI  - The anatomic basis for the acquisition of speech and obstructive sleep apnea:
      evidence from cephalometric analysis supports The Great Leap Forward hypothesis.
AB  - BACKGROUND AND PURPOSE: We previously postulated how evolutionary changes in
      man's upper respiratory tract to facilitate speech, a phenomenon Jared Diamond
      calls The Great Leap Forward, have predisposed man to obstructive sleep apnea
      (OSA) [Diamond J. The Third Chimpanzee: the evolution and future of the human
      animal. New York: HarperCollins Publishers; 1992. p. 21, 23, 32-54, 54-6;
      Davidson TM. The Great Leap Forward: the anatomic evolution of obstructive sleep
      apnea. Sleep Medicine 2003;4:185-94]. We grouped these anatomic changes into four
      categories: klinorynchy, laryngeal descent, craniobase angulation and
      supralaryngeal vocal tract (SVT) ratio of SVT(H):SVT(V). This study was designed
      to investigate the relationship between cephalometric measures corresponding to
      these anatomic changes and OSA. PATIENTS AND METHODS: One hundred and twenty
      three male subjects presenting with symptoms of OSA underwent unattended multi
      channel home sleep studies. We obtained cephalometric measurements from standard
      lateral cephalograms. Pearson correlation coefficients were calculated between
      cephalometrics and apnea-hypopnea index (AHI), age, and body mass index (BMI).
      RESULTS: Our results showed significant correlation between AHI and klinorynchy,
      laryngeal descent, and craniobase angulation. CONCLUSIONS: Overall, our data
      supports the theory that evolutionary anatomic changes to facilitate speech
      correlate with OSA severity. The cumulative changes in each cephalometric
      category trended in the directions hypothesized and support the Great Leap theory
      of OSA evolution.

PMID- 15994121
TI  - Partial sleep deprivation therapy combined with sertraline affects subjective
      sleep quality in major depressive disorder.
AB  - BACKGROUND AND PURPOSE: Earlier studies have shown an association between mood
      disorders and sleep regulation. Total or partial sleep deprivation was
      demonstrated to have rapid antidepressive effects in depression. Depressive
      symptoms recur after one night of recovery sleep, but relapse is less when
      patients are receiving medication. In this study, we examined the subjective
      sleep quality changes with the antidepressive therapy using partial sleep
      deprivation plus sertraline and sertraline monotherapy in patients with major
      depressive disorder. PATIENTS AND METHODS: Thirteen patients received six partial
      sleep deprivation therapies in addition to sertraline; the sleep schedule on
      deprivation nights started at 11:00 p.m. and ended at 3:00 a.m. Eleven patients
      were treated with sertraline monotherapy as a control group. Six nights of
      partial sleep deprivation were completed in the first two weeks. Subjective sleep
      quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI); depression
      and the accompanying anxiety were also assessed at baseline and at the end of the
      fourth week. RESULTS: The late partial sleep deprivation (LPSD) group showed less
      increase in estimated sleep duration and less significant improvement in
      subjective sleep quality than the control group. Although decreased sleep latency
      and increased sleep efficiency are associated with the sleep deprivation,
      contrary results were found in our study. CONCLUSIONS: In conclusion, changes in
      subjective sleep quality could occur relative to the combined partial sleep
      deprivation therapy and to pharmacotherapy and must be differentiated from the
      rapid effects of sleep deprivation therapy and objective polysomnographic
      measures.

PMID- 15994122
TI  - Non-REM-sleep instability in recurrent sleepwalking in pre-pubertal children.
AB  - BACKGROUND AND PURPOSE: We questioned whether or not the sleep of pre-pubertal
      children with recurrent sleepwalking was different from that recorded in normal
      children. PATIENTS AND METHODS: Twelve pre-pubertal chronic sleepwalkers were
      compared to age- and gender-matched normal children. All children had a clinical
      evaluation covering pediatric, sleep, neuropsychiatric and otolaryngological
      fields. Two standardized sleep questionnaires were administered, and a minimum of
      two successive polysomnograms were performed with monitoring of sleep
      electroencephalographic (EEG) and cardiorespiratory variables. The research
      investigations were performed on nights without sleepwalking to search for the
      presence of other sleep disorders, including upper airway resistance syndrome
      (UARS). Sleep was scored using standard atlases, but it was also evaluated for
      the cyclic alternating pattern (CAP) rate. RESULTS: All sleepwalkers presented
      with either obstructive sleep apnea (n=2) or UARS (n=10). Compared to normal
      children, sleepwalkers had shorter total sleep time but no significant change in
      wake after sleep onset when considering all arousals > 3 s. CAP analysis showed a
      significantly higher CAP rate than in controls. CONCLUSIONS: Chronic sleepwalkers
      have instability of non-rapid eye movement (NREM) sleep detectable only by the
      calculation of CAP rate. Instability of NREM sleep was seen even on nights
      without sleepwalking and is probably related to the presence of the associated
      sleep disorders. We hypothesize that chronic NREM-sleep instability is a risk
      factor for occurrence of sleepwalking when further sleep disruption is triggered
      by external events.

PMID- 15994123
TI  - Reevaluating spells initially identified as cataplexy.
AB  - BACKGROUND AND PURPOSE: Cataplexy, transient episodes of bilateral muscle
      weakness with areflexia provoked by emotions, is a state highly specific to
      narcolepsy. Cataplexy is diagnosed based on clinical interview. Two screening
      tools have been developed recently but their usefulness has been limited because
      of length or current lack of psychometric data. Used effectively even these
      screening tests require the interpreting physician to have an understanding of
      the typical features of cataplexy. Most physicians encounter patients with
      cataplexy fairly infrequently, making it difficult to gain proficiency in
      detecting cataplexy based on clinical interview alone. Relatively little
      attention has been given to the differential diagnosis of cataplexy, which
      increases the likelihood of unnecessary sleep testing or false positive
      diagnosis. PATIENTS AND METHODS: This case series describes six cases where
      cataplexy was initially diagnosed. In all cases the weakness spells were
      eventually not attributed to cataplexy. The presentation and characteristics of
      these cases will be presented as a means to discuss the differential diagnosis of
      cataplexy. RESULTS: These cases represent a diverse set of medical disorders
      including bradycardia, migraine, delayed sleep phase syndrome, conversion
      disorder, malingering and a chronic psychotic disorder. CONCLUSIONS: A more in
      depth understanding of the classic features of cataplexy should improve
      recognition of this fascinating state. Improved cataplexy recognition will
      enhance the appropriate usage of sleep tests and eventually increase the
      timeliness and accuracy of the diagnosis of narcolepsy with cataplexy.

PMID- 15994124
TI  - Heart rate variability, sympathetic and vagal balance and EEG arousals in upper
      airway resistance and mild obstructive sleep apnea syndromes.
AB  - BACKGROUND AND PURPOSE: We questioned the role of respiratory events in
      obstructive sleep apnea syndrome (OSAS) and of upper airway resistance syndrome
      (UARS) on heart rate (HR) during sleep, paying specific attention to the
      termination of the abnormal breathing events and examining the presence of
      arousals or termination with only central nervous system (CNS) activation.
      PATIENTS AND METHODS: Twenty patients, 10 with UARS and 10 with mild OSAS, were
      studied. A nocturnal polysomnogram was performed including measurement of
      respiratory variables and pulse transit time (PTT). According to the presence or
      absence of a PTT event indicative of autonomic nervous system (ANS) activation,
      148 events were extracted after having been randomly chosen in each represented
      sleep stage, with or without an electroencephalogram (EEG) arousal >1.5s. RR
      interval (RRI) in electrocardiogram (ECG) recordings, as well as heart rate
      variability, was calculated during 60 and 120s, respectively. Period amplitude
      analysis (PAA) was applied for RR-interval analysis, and fast Fourier
      transformation (FFT) was applied to perform HR variability analysis. RESULTS:
      Visually scored EEG arousal was significantly associated with an increase in
      sympathetic index of heart rate, while PTT was associated with a drop in
      parasympathetic index, after the respiratory events. Patients with mild OSAS
      presented persistently shorter RRI when compared to patients with UARS. The
      latter also exhibited a significant decrease in parasympathetic index (High
      Frequency (HF)) at the termination of a respiratory event. CONCLUSION: The HF
      component was only significantly decreased in patients with UARS, which indicates
      a predominant involvement of the parasympathetic tone in patients with UARS in
      comparison to those with OSAS.

PMID- 15994125
TI  - Insomnia treatment: measuring the elusive daytime impairment.

PMID- 15994126
TI  - Is insomnia a marker for psychiatric disorders in general hospitals?
AB  - BACKGROUND AND PURPOSE: The aim was to evaluate the relationship between insomnia
      and psychiatric disorders in general hospital inpatients. PATIENTS AND METHODS:
      Information about insomnia was collected using a structured and codified
      questionnaire adapted from a previously validated one in Brazil. For Diagnostic
      and Statistical Manual of Mental Disorders IV (DSM-IV) psychiatric diagnosis, the
      Portuguese version of the International Neuropsychiatric Interview (MINI) was
      used. RESULTS: Out of the 200 patients interviewed, 56.5% complained of insomnia,
      and 50.0% suffered from at least one psychiatric disorder. Major depressive
      episode (MDE) (P<0.001), generalized anxiety disorder (P=0.025) and suicide risk
      (P=0.034) were associated with insomnia (univariate analysis). The results of the
      multivariate analysis showed that only MDE had a statistically significant
      association with insomnia (OR=3.6; 95% CI=1.9-6.9). CONCLUSIONS: This study found
      a high prevalence of psychiatric disorders and insomnia in a general hospital
      population and found that insomnia can be a marker for MDE.

PMID- 15994127
TI  - Voxel-based morphometry in narcolepsy.
AB  - BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) is a magnetic resonance
      imaging (MRI)-based indirect volumetry, which allows the investigation of the
      entire brain without restriction of predefined regions-of-interest. Recent
      studies using this technique reported controversial results in patients with
      narcolepsy. PATIENTS AND METHODS: In this study, 12 patients with narcolepsy
      according to the criteria of the International Classification of Sleep Disorders
      were compared to 12 age-matched controls with normal MR images using VBM. Sex and
      global differences in voxel intensities were used as confounding covariates.
      RESULTS: Significant gray matter loss was found in the right prefrontal and
      frontomesial cortex of patients with narcolepsy. White matter comparison revealed
      no significant changes in patients or controls. The comparison of cerebrospinal
      fluid partition detected an enlargement of subarachnoidal space of controls close
      to the prefrontal cortex. CONCLUSIONS: The volume reduction of gray matter in
      narcoleptic patients could indicate a disease-related atrophy pattern. However,
      the results of VBM studies in narcolepsy are contradictory. A possible systematic
      bias due to inhomogeneous patient groups, stimulant medication history or pre
      statistical image processing must be considered. We suggest that studies with
      drug-naive patients and/or region-of-interest-based volumetric studies should be
      performed in areas defined by VBM.

PMID- 15994128
TI  - Identification of B cell epitopes recognized by antibodies specific for the tumor
      antigen NY-ESO-1 in cancer patients with spontaneous immune responses.
AB  - Expression of the germ line antigen NY-ESO-1 in adult somatic tissues other than
      testis is strictly found in association with cancer. Patients bearing NY-ESO-1
      expressing tumors often develop integrated specific immune responses to the
      antigen, encompassing T cell and antibody responses. Hence, detection of NY-ESO-1
      specific antibody responses can be considered as a cancer biomarker of great
      interest. Here, we used synthetic peptides spanning the sequence of the NY-ESO-1
      protein to assess antibody responses in cancer patients. This approach allowed
      the identification of peptides containing linear B cell epitopes. Some peptides
      were recognized by the majority of seropositive patients thus identifying several
      distinct regions of the protein containing frequently recognized B cell epitopes.
      The results of this study provide the first appraisal of the diversity of
      naturally-occurring NY-ESO-1 specific antibodies and could be instrumental in the
      monitoring of therapy-induced antibody responses in cancer patients receiving NY
      ESO-1-based vaccines.

PMID- 15994129
TI  - Coronary artery-left ventricular fistulae associated with apical hypertrophic
      cardiomyopathy.
AB  - We describe an unusual case of coronary artery-left ventricular fistulae
      associated with apical hypertrophic cardiomyopathy in a 63-year-old man who had a
      2-year history of angina pectoris without significant coronary atherosclerosis.
      It is important to recognize this anomaly as it may be the source of angina in
      patients without angiographic evidence of major atherosclerotic coronary artery
      disease.

PMID- 15994130
TI  - Characterization of four different effects elicited by H2O2 in rat aorta.
AB  - Four main vascular effects of hydrogen peroxide (H2O2) were studied in intact and
      rubbed aortic rings from WKY rats. In rings partially precontracted with
      phenylephrine: 1-30 microM H2O2 induced an increase of tone, 100 microM H2O2
      produced a transient contraction followed by a fast-developing endothelium
      independent relaxation, and 0.3 mM H2O2 induced a fast-developing relaxation
      followed by a slow-developing endothelium-independent relaxation. Superoxide
      dismutase (SOD) or dimethyl sulfoxide (DMSO)/manitol did not significantly modify
      the H2O2 effects, while catalase suppressed them. Indomethacin abolished the
      increase of tone elicited by H2O2 and revealed a small endothelium-dependent
      relaxation, which was suppressed by N(G)-nitro-L-arginine (L-NA), high K+ or
      tetraethylammonium (TEA). TEA strongly inhibited the fast-developing relaxation
      while indomethacin, glybenclamide, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ), cafeic acid or eicosatriynoic acid (ETI) did not affect the relaxation. In
      rings precontracted with 70 mM KCl, 1-100 microM H2O2 induced a small increase of
      tone and 0.3 mM a slow-developing relaxation. Catalase or Fe2+-EDTA/vitamin C
      suppressed the slow-developing relaxation while deferoxamine did not modify it.
      In rings partially precontracted with arachidonic acid, 1-30 microM H2O2 induced
      higher contractile effects than in rings partially precontracted with
      phenylephrine. H2O2 at 0.3 mM for one hour induced a persistent impairment on the
      reactivity of the rings and the release of lactate dehydrogenase. In summary,
      H2O2 produces: (1) contractions mediated by direct activation of cyclooxygenase;
      2) endothelium-dependent relaxations related to activation of endothelial K+
      channels and NO synthesis; 3) reversible endothelium-independent relaxations
      mediated by activation of smooth muscle K+ channels; and 4) irreversible
      endothelium-independent relaxations related to cellular damage, caused by H2O2
      but not by hydroxyl radicals.

PMID- 15994131
TI  - Electron transfer reactivity and the catalytic activity of horseradish peroxidase
      incorporated in dipalmitoylphosphatidic acid films.
AB  - Horseradish peroxidase (HRP) was incorporated in dipalmitoylphosphatidic acid
      (DPPA) to form a film and the film was modified on pyrolytic graphite electrode.
      UV-Vis spectra suggested that HRP in the film could keep its secondary structure
      similar to the native state. A pair of stable, well-defined, and quasi-reversible
      cyclic voltammetric peaks was observed with the formal potential at -276.2 mV
      (vs. saturated calomel electrode), characteristic of heme Fe(III)/Fe(II) redox
      couple of HRP. The apparent heterogeneous electron transfer rate constant and
      other electrochemical parameters were presented. The catalytic activity of HRP in
      DPPA film toward oxygen, hydrogen peroxide and nitric oxide were also examined.

PMID- 15994132
TI  - A non-radioactive, PFGE-based assay for low levels of DNA double-strand breaks in
      mammalian cells.
AB  - A PFGE method was adapted to measure DNA double-strand breaks (DSBs) in mammalian
      cells after low (0-25 Gy) doses of ionising radiation. Instead of radionuclide
      incorporation, DNA staining in the gel by SYBR-Gold was used, which lowered the
      background of DNA damage and could be applied to non-cycling cells. DSB level was
      defined as a product of a fraction of DNA released to the gel (FR) and a number
      of DNA fragments in the gel (DNA(fragm)) and expressed as a percentage above
      control value. The slope of the dose-response curve was two-fold higher compared
      to that with FR alone as DSB level indicator (31.4 versus 15.6% per Gy). Two
      alternative ways were proposed to determine the total amount of DNA, used for FR
      calculation: measurement of DNA content in a plug not subjected to
      electrophoresis, with the use of Pico-Green, or estimation of DNA released to the
      gel from a plug irradiated with 600 Gy of gamma-rays. The limit of DSB detection
      was 0.25 Gy for human G1-lymphocytes and 0.5-1 Gy for asynchronous cultures of
      human glioma M059 K and J or mouse lymphoma L5178Y-R and -S cells. Specificity of
      our PFGE assay to DSB was confirmed by the fact that no damage was detected after
      treatment of the cells with H(2)O(2), an inducer of single-strand DNA breaks
      (SSBs). On the contrary, the H(2)O(2) inflicted damage was detected by neutral
      comet assay, attaining 160% above control (equivalent to 2.5 Gy of X-radiation).
      DSB rejoining, measured in cells after X-irradiation with a dose of 10 Gy,
      generally proceeded faster than that measured previously after higher (30-50 Gy)
      doses of ionising radiation. Clearly seen were defects in DSB rejoining in
      radiosensitive M059 J and L5178Y-S cells compared to their radioresistant
      counterparts, M059 K and L5178Y-R. In some cell lines, a secondary post
      irradiation increase in DSB levels was observed. The possibility is considered
      that these additional DSBs may accumulate during processing of non-DSB clustered
      DNA damage or/and represent early apoptotic events.

PMID- 15994133
TI  - Measurement of tobramycin and gentamicin in saliva is not suitable for
      therapeutic drug monitoring of patients with cystic fibrosis.

PMID- 15994134
TI  - The distribution of ventilation during bronchoconstriction is patchy and bimodal:
      a PET imaging study.
AB  - Recent PET imaging data from bronchoconstricted sheep (Vidal Melo et al., 2005)
      showed that V /Q distributions were bimodal and topographically patchy, but
      including a substantial heterogeneity at scales <2.2 ml. In this paper, we
      reanalyze the experimental data to establish the contribution of ventilation (V
      (r)) heterogeneity to the bimodality in V /Q . This analysis demonstrates that
      the distribution of V (r) during bronchoconstriction was bimodal with large
      patches of severe hypoventilation occupying an average of 41% of the imaged lung.
      The degree of hypoventilation to these regions was highly correlated with the
      degree of oxygenation impairment, but was quite variable amongst animals in spite
      of consistent degrees of mechanical obstruction. Remarkably, those regions were
      found to be hyperventilated before methacholine and their degree of
      hyperventilation was correlated with their degree of hypoventilation during
      bronchoconstriction. These data suggest that improving the uniformity of
      ventilation at baseline may be a desirable therapeutic target if the risk of
      severe hypoxemia during asthma attacks is to be minimized and/or the distribution
      of inhaled pharmaceuticals is to be optimized.

PMID- 15994135
TI  - Effects of nicotine on rat sternohyoid muscle contractile properties.
AB  - Obstructive sleep apnoea (OSA) is a major clinical disorder characterised by
      recurring episodes of pharyngeal collapse during sleep. At present, there remains
      no satisfactory treatment for OSA. Pharmacological therapies as a potential
      treatment for the disorder are an attractive option and include agents that
      increase the contractility of the pharyngeal muscles. The aim of the present
      study was to examine the effects of nicotine on upper airway muscle contractile
      properties. In vitro isometric contractile properties were determined using
      strips of rat sternohyoid muscle in physiological salt solution containing
      nicotine (0-100 microg/ml) at 25 degrees C. Isometric twitch and tetanic tension,
      contraction time, half-relaxation time and tension-frequency relationship were
      determined by electrical field stimulation with platinum electrodes. Fatigue was
      induced by stimulation at 40 Hz with 300 ms trains at a frequency of 0.5 Hz for 5
      min. Nicotine at a concentration of 1 microg/ml was associated with a significant
      increase in sternohyoid muscle specific tension compared to control data. Dose
      dependent increases in contractile tension were not observed. Nicotine had
      effects on tension-frequency relationship and endurance properties of the
      sternohyoid muscle at some but not all doses. A leftward shift in the tension
      frequency relationship was observed at low stimulus frequencies (20-30 Hz) for
      nicotine at a concentration of 1 and 5 microg/ml and a significant increase in
      fatigue resistance was observed with nicotine at a concentration of 10 microg/ml.
      As fatigue of the upper airway muscles has been implicated in obstructive airway
      conditions, a pharmacological agent that improves muscle endurance may prove
      useful as a potential treatment for such disorders. Therefore, further studies of
      the effects of nicotinic agonists on upper airway function are warranted.

PMID- 15994137
TI  - Biochemical and molecular modeling analysis of the ability of two p
      aminobenzamidine-based sorbents to selectively purify serine proteases
      (fibrinogenases) from snake venoms.
AB  - Snake venoms contain several trypsin-like enzymes with equivalent physicochemical
      characteristics and similar inhibition profiles. These are rather difficult to
      separate by classical purification procedures and therefore constitute a good
      model for affinity chromatography analysis. Some of these trypsin homologues
      present fibrinogenase activity, mimicking one or more features of the central
      mammalian coagulation enzyme, thrombin. It was previously demonstrated that a
      number of amidine derivatives are able to interact specifically with some of
      these serine proteases. To understand the enzyme-sorbent interactions we have
      investigated the ability of two commercially available benzamidine affinity
      matrices to purify thrombin-like serine proteases (TLSP) with similar biological
      properties from two snake venoms (Bothrops jararacussu and Lachesis muta
      rhombeata). Curiously, each sorbent retained a single but distinct TLSP from each
      venom with high yield. Molecular modeling analysis suggested that hydrophobic
      interactions within a specific region on the surface of these enzymes could be
      generated to explain this exquisite specificity. In addition, it was demonstrated
      that a specific tandem alignment of the two benzamidine sorbents enables the
      purification of three other enzymes from B. jararacussu venom.

PMID- 15994138
TI  - Direct liquid chromatography determination of the reactive imine SJG-136 (NSC
      694501).
AB  - SJG-136 (NSC 694501), 8,8'-[[(propane-1,3-diyl)dioxy]bis[(11aS)-7-methoxy-2
      methylidene-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one],
      which is being developed as a DNA-interactive antitumor agent, contains highly
      reactive imines in the diazepinone portions of the molecule. Water or alcohol
      adds readily to the imino moiety to form the corresponding carbinolamine or its
      alkyl ether, respectively. This sensitivity to protic substances poses a
      formidable challenge to the formulation and HPLC assay development for the
      compound. After studying the solution chemistry of SJG-136 and its potential
      interaction with various stationary phases, two reversed-phase liquid
      chromatographic assays for the compound have been developed. A direct assay that
      separates SJG-136 from its water or methanol adducts and an indirect assay that
      quantifies SJG-136 as its dihydrate adduct are reported. The latter method, which
      is more practical for drug development, has been validated. It is reproducible
      (R.S.D.<2%), linear (r2=0.9999) and accurate (within 98-102% recovery), with a
      lower detection limit of 2.5 ng.

PMID- 15994136
TI  - Determination of 8-oxoguanine and 8-hydroxy-2'-deoxyguanosine in the rat cerebral
      cortex using microdialysis sampling and capillary electrophoresis with
      electrochemical detection.
AB  - A rapid and sensitive method to determine 8-oxoguanine (8oxoG) and 8
      hydroxydeoxyguanosine (8OHdG), biomarkers for oxidative DNA damage, in cerebral
      cortex microdialysate samples using capillary electrophoresis (CE) with
      electrochemical detection (CEEC) was developed. Samples were concentrated on
      column using pH-mediated stacking for anions. On-column anodic detection was
      performed with a carbon fiber working electrode and laser-etched decoupler. The
      method is linear over the expected extracellular concentration range for 8oxoG
      and 8-OHdG during induced ischemia-reperfusion, with R.S.D. values <or=5% and
      limit of detection of 0.5 nM for both analytes. Basal concentrations of 8oxoG in
      rat cerebral cortex microdialysate were determined to be 3.2+/-0.6 nM. Actual
      8oxoG concentration in the brain was estimated to be 5.5+/-1.3 nM based on in
      vivo delivery probe calibration. 8OHdG was not detected under basal conditions in
      the rat cerebral cortex extracellular fluid (ECF). These results were confirmed
      by LC with tandem mass spectrometry.

PMID- 15994139
TI  - Determination of chlorpyrifos metabolites in human urine by reversed-phase/weak
      anion exchange liquid chromatography-electrospray ionisation-tandem mass
      spectrometry.
AB  - A liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI
      MS/MS) method for the quantification of major chlorpyrifos (CP) metabolites, i.e.
      diethyl thiophosphate (DETP), diethyl phosphate (DEP), and 3,5,6-trichloro-2
      pyridinol (TCP), in human urine was developed. Simultaneous separation of the
      parent compound and its primary biotransformation products was achieved within 20
      min in gradient elution mode employing a mixed-mode reversed-phase/weak anion
      exchange (RP/WAX) separation principle. The analytical method was developed for a
      toxicokinetic study of an acute poisoning incidence with a CP containing
      pesticide formulation. An initial mass spectrometric screening performed with
      unprocessed urine samples revealed that CP is not excreted unchanged by the
      kidney. Hence, the quantitative assay was validated for DETP (quantifier
      transition: m/z 169-->95, qualifier transition: m/z 169-->141), DEP (m/z 153-
      >79, 153-->125), and TCP (m/z 196-->35, 198-->35) taking dibutyl phosphate (DBP)
      (m/z 209-->79, 209-->153) as internal standard. Clean-up of urine samples prior
      to LC-ESI-MS/MS analysis was carried out by a liquid-liquid extraction step with
      a mixture of ethylacetate and acetonitrile (70:30; v/v). Linearity was observed
      between 0.25 and 75 mgL(-1), and the signal-to-noise ratio at 0.25 mgL(-1) was
      better than six for the individual analytes. Recoveries, precision, and
      accuracies were all adequate across the validated range of 1-75 mgL(-1) for the
      present toxicological case study.

PMID- 15994140
TI  - A hybrid LC-Gel-MS method for proteomics research and its application to protease
      functional pathway mapping.
AB  - Two-dimensional (2D) gel electrophoresis is the most common protein separation
      method in proteomics research. It can provide high resolution and high
      sensitivity. However, 2D gel methods have several limitations, such as labor
      intensive procedures, poor reproducibility, and limited dynamic range of
      detection. In fact, many investigators have returned to couple the one
      dimensional (1D) SDS-PAGE with mass spectrometry for protein identification. The
      limitation of this approach is the increased protein complexity in each one
      dimensional gel band. To overcome this problem and provide reproducible
      quantitative information, we describe here a 2D method for protein mixture
      separation using a combination of high performance liquid chromatography (HPLC)
      and 1D SDS-PAGE. The study shows that the step-gradient fractionation method we
      have applied provides excellent reproducibility. In addition, high mass accuracy
      of LC-FTICR-MS can allow more confident protein identifications by high
      resolution and ultra-high mass measurement accuracy. This approach was applied to
      comparative proteomics since protein abundance level changes can be easily
      visualized with side-by-side vertical comparison in one gel. Furthermore,
      separation of multi-samples in the same gel significantly reduces run-to-run
      variation, as is shown with differential image gel electrophoresis (DIGE).
      Finally, this approach readily incorporates immunological methods to normalize
      relative abundances of multiple samples within a single gel. This paper presents
      the results of our developments and our initial application of this strategy for
      mapping protease function of beta amyloid cleaving enzyme (BACE) in biological
      systems.

PMID- 15994141
TI  - Childhood influences on youth obesity.
AB  - We develop a model to estimate the influence of child and parental
      characteristics on the likelihood that a child will become an obese or overweight
      youth. We use this model to test whether it is possible to forecast obesity and
      overweight among youth. Comparing Receiver Operating Characteristic (ROC) scores
      from these forecasts, we find that a model using childhood covariates does as
      well in forecasting youth obesity and overweight as a model using the covariate
      values contemporaneous with the youth obesity and overweight outcomes. The
      datasets used in this paper, the National Longitudinal Survey of Youth (NLSY79)
      and the NLSY79 Children and Young Adults, provide data from 1986 to 2002,
      allowing for the study of a child's transition to and from obesity or overweight
      over a long period. Explanatory variables that significantly influence the
      likelihood of youth obesity or overweight outcomes include the mother's obesity
      status and education, the youth's mental health, and certain demographic features
      including race, sex, and family size. These factors provide potential targets for
      policies that could be implemented early in life among children most likely to
      become obese or overweight.

PMID- 15994142
TI  - Comparison of HER2 status by fluorescence in situ hybridization and
      immunohistochemistry to predict benefit from dose escalation of adjuvant
      doxorubicin-based therapy in node-positive breast cancer patients.
AB  - PURPOSE: HER2 is a clinically important tumor marker in breast cancer; however,
      there is controversy regarding which method reliably measures HER2 status. We
      compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence
      in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict
      disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin
      based therapy in node-positive breast cancer patients. METHODS: This is a Cancer
      and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast
      cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO
      11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR
      utilized differential PCR (D-PCR) methodology. RESULTS: Cases HER2 positive by
      IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were
      clearly related (kappa = 64.8%). All three methods demonstrated a similar
      relationship for DFS and OS. By any method, for patients with HER2-negative
      tumors, there was little or no effect of dose of adjuvant doxorubicin-based
      therapy. For patients with HER2-positive tumors, all three methods predicted a
      benefit from dose-intense (high-dose) compared with low- or moderate-dose
      adjuvant doxorubicin-based therapy. CONCLUSION: FISH is a reliable method to
      predict clinical outcome following adjuvant doxorubicin-based therapy for stage
      II breast cancer patients. There is a moderate level of concordance among the
      three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although
      IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of
      therapy in predicting outcome, no combination of assays tested was statistically
      superior.

PMID- 15994143
TI  - Interventions to enhance physical and psychological functioning among younger
      women who are ending nonhormonal adjuvant treatment for early-stage breast
      cancer.
AB  - PURPOSE: To conduct a clinical trial to determine if an educational intervention
      and a nutritional intervention could enhance physical and psychological
      functioning among younger women completing treatment for early-stage breast
      cancer. PATIENTS AND METHODS: Younger women (50 years of age or younger, N =
      252), within 2 months of having completed active nonhormonal adjuvant therapy,
      diagnosed with stage 0, I, or II breast cancer with 10 or fewer positive lymph
      nodes were randomly assigned to a three-arm clinical trial. Women in the control
      arm of the trial received standard medical care. Women in the two active arms
      received either an educational intervention, designed to provide information
      about their illness and enhance adjustment, or a nutritional intervention,
      designed to promote a more healthy diet. Primary end points included mental
      functioning, physical functioning, and depressive symptoms. Women were assessed
      before random assignment, 4 months later (immediately post-intervention), and 13
      months later (9 months post-intervention). RESULTS: Participants assigned to the
      two active treatment arms had significantly less depressive symptomatology and
      better physical functioning by 13-month follow-up (differences between the two
      active arms were nonsignificant). These effects were primarily accounted for by
      changes in intrusive thoughts, concerns regarding cancer recurrence and
      mortality, self-concept perceptions, and self-efficacy expectations. CONCLUSION
      Tailored psychosocial interventions can be effectively designed to enhance
      adjustment among younger women who are completing nonhormonal adjuvant therapy.

PMID- 15994144
TI  - Morbidity after sentinel lymph node biopsy in primary breast cancer: results from
      a randomized controlled trial.
AB  - PURPOSE: Axillary lymph node dissection (ALND) as part of surgical treatment for
      patients with breast cancer is associated with significant morbidity. Sentinel
      lymph node biopsy (SLNB) is a newly developed method of staging the axilla and
      has the potential to avoid an ALND in lymph node-negative patients, thereby
      minimizing morbidity. The aim of this study was to investigate physical and
      psychological morbidity after SLNB in the treatment of early breast cancer in a
      randomized controlled trial. PATIENTS AND METHODS: Between November 1999 and
      February 2003, 298 patients with early breast cancer (tumors 3 cm or less on
      ultrasound examination) who were clinically node negative were randomly allocated
      to undergo ALND (control group) or SLNB followed by ALND if subsequently found to
      be lymph node positive (study group). A detailed assessment of physical and
      psychological morbidity was performed during a 1-year period postoperatively.
      RESULTS: A significant reduction in postoperative arm swelling, rate of seroma
      formation, numbness, loss of sensitivity to light touch and pinprick was observed
      in the study group. Although shoulder mobility was less impaired on average in
      the study group, this was significant only for abduction at 1 month and flexion
      at 3 months. Scores reflecting quality of life and psychological morbidity were
      significantly better in the study group in the immediate postoperative period,
      with fewer long-term differences. CONCLUSION: SLNB in patients undergoing surgery
      for breast cancer results in a significant reduction in physical and
      psychological morbidity.

PMID- 15994145
TI  - Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma.
AB  - PURPOSE: Randomized studies on tamoxifen treatment of hepatocellular carcinoma
      (HCC) produced conflicting results. The aim of this study was to assess the
      efficacy of tamoxifen administration in improving overall survival of patients
      with advanced HCC. PATIENTS AND METHODS: A total of 420 patients with HCC who
      were not suitable for surgery or local treatment were randomly assigned between
      April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group
      (20 mg/d orally). Patients with WHO performance status greater than 2, belonging
      to Child-Pugh class C, or with serum creatinine greater than 130 mumol/L were not
      eligible. RESULTS: Tolerance was good and the main reported adverse effects were
      thrombophlebitis (three patients), nausea (two patients), and hot flushes (three
      patients). Outcome did not differ between the two treatment arms: estimated
      median survival was 4.8 and 4.0 months in the tamoxifen and in the control
      groups, respectively (P = .25). Univariate analysis showed significant
      association of survival with age, Okuda stage, WHO performance status, Child-Pugh
      class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and
      presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or
      hepatalgia. In a Cox proportional hazards model we found a significant beneficial
      effect of tamoxifen on survival in patients belonging to Okuda I or II stages.
      CONCLUSION: In this large study, tamoxifen did not improve the survival of
      patients with advanced HCC, but there is a suggestion that patients without major
      hepatic insufficiency seem to have some survival benefit. New trials involving
      this specific population are warranted.

PMID- 15994146
TI  - Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life:
      experience of the International Society of Pediatric Oncology (SIOP) Malignant
      Mesenchymal Tumor Committee.
AB  - PURPOSE: To describe the outcome of infants with a histologically confirmed
      diagnosis of malignant mesenchymal tumor (MMT) included in the International
      Society of Paediatric Oncology studies MMT 84 and MMT 89. PATIENTS AND METHODS:
      One hundred two infants (< or = 12 months old) were included. Twenty-four
      children were less than 3 months old, and 16 were less than 1 month old. Sixty
      four patients had rhabdomyosarcoma (RMS), 26 had undifferentiated sarcoma, and 12
      had other histology. Clinical TNM stage was stage I (41%), II (39%), III (6%),
      and IV (14%). First-line treatment was ifosfamide, vincristine, dactinomycin,
      whereas the second-line combination consisted of either cisplatin and doxorubicin
      (in MMT 84) or vincristine, carboplatin, etoposide/teniposide (in MMT 89).
      Chemotherapy doses were adapted to age. Local therapy was conservative surgery as
      often as possible. RESULTS: After a median follow-up of 7.8 years (range, 0.1 to
      13 years), 5-year overall survival (OS) and event-free survival rates were 66%
      and 55% for the total study population and 72% and 60% for nonmetastatic
      patients, respectively. Only two of 13 stage IV patients survived. Sixty-seven
      percent of newborn infants survived. Infants with alveolar subtype had a poorer
      survival than those with non-RMS MMT or nonalveolar RMS (5-year OS, 37% v 75% or
      82%, respectively; P = .002). When compared with older children with MMT, young
      age does not seem to be an important prognostic factor. CONCLUSION: OS was
      satisfactory even when local treatment was not aggressive, although the prognosis
      was poor for infants with alveolar RMS or metastatic tumors. Chemotherapy
      toxicity was manageable with appropriate dose modification.

PMID- 15994147
TI  - Prognostic factors and outcome of human herpesvirus 8-associated primary effusion
      lymphoma in patients with AIDS.
AB  - PURPOSE: Primary effusion lymphoma (PEL) is a rare high-grade B-cell non
      Hodgkin's lymphoma associated with Kaposi sarcoma-associated herpesvirus/human
      herpesvirus 8 (KSHV/HHV-8) infection, and is mostly observed in the course of HIV
      infection. The prognosis is poor, with reported median survival time shorter than
      6 months. To date, no prognostic factor has been identified in this subset of
      lymphoma. PATIENTS AND METHODS: We describe here a large series of HIV-infected
      patients with PEL, including 28 cases diagnosed in six centers during an 11-year
      time period. Prognosis analysis was performed using a Cox proportional hazard
      regression model. Statistically significant covariates were further analyzed in a
      forward, stepwise multivariate model. RESULTS: After a median follow-up of 3.8
      years (range, 10 months to 10.8 years), nine patients (32%) were still alive, and
      eight of them remained progression free. The median survival was 6.2 months, and
      the 1-year overall survival rate was 39.3%. Fourteen patients (50%) achieved
      complete remission, with a 1-year disease-free survival rate at 78.6%. In a
      multivariate analysis, only a performance status more than 2 (hazard ratio, 5.84;
      95% CI, 1.76 to 19.33) and the absence of highly active antiretroviral therapy
      (HAART) before PEL diagnosis (hazard ratio, 3.26; 95% CI, 1.14 to 9.34) were
      found to be independent predictors for shorter survival. CONCLUSION: Based on a
      retrospective series of 28 patients, two prognostic factors were identified as
      being independently associated with impaired clinical outcome in HIV-related PEL-
      (1) a poor performance status and (2) the absence of HAART before PEL diagnosis.

PMID- 15994148
TI  - Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory
      follicular lymphoma.
AB  - PURPOSE: This multicenter, dose-escalation study evaluates the safety,
      pharmacokinetics, and efficacy of galiximab (anti-CD80 monoclonal antibody) in
      patients with relapsed or refractory follicular lymphoma. PATIENTS AND METHODS:
      Patients had follicular lymphoma that had relapsed or failed to respond to
      primary therapy; the majority (90%) presented with stage III or IV disease. Four
      weekly intravenous infusions of galiximab were administered at doses of 125, 250,
      375, or 500 mg/m2. RESULTS: Thirty-seven patients received galiximab treatment
      and were evaluated for safety; 35 were assessable for response. Antibody
      infusions were safe and well tolerated with no dose-limiting toxicities. A total
      of 22 (60%) of 37 patients experienced adverse events related to galiximab. All
      but one of the events were grade 1 or 2; the most common were fatigue, nausea,
      and headache. Cytopenias were rare; only one patient experienced anemia and
      febrile neutropenia, which were unrelated to galiximab and resolved after
      treatment. No patient developed antigaliximab antibody formation. The mean serum
      half-life ranged from 13 to 24 days. The overall response rate was 11% (two
      complete responses and two partial responses). Time to best response was delayed
      (months 3, 6, 9, and 12). Twelve patients (34%) maintained stable disease. Nearly
      half of all patients (49%) had a decrease in indicator lesions. Two responders
      remain on study without progression (22 and 24.4 months). CONCLUSION: The
      favorable safety profile of galiximab and evidence of single-agent biologic
      activity and dose-dependent pharmacokinetics support further evaluation of
      galiximab as a treatment for follicular lymphoma, possibly in combination with
      other lymphoma therapies.

PMID- 15994149
TI  - Quality of life of long-term survivors of breast cancer and lymphoma treated with
      standard-dose chemotherapy or local therapy.
AB  - PURPOSE: This study compared the quality of life (QOL) of long-term survivors of
      breast cancer and lymphoma who had been treated with standard-dose systemic
      chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors
      (mean, 10.0 +/- 5.3 years after treatment) of breast cancer or lymphoma who had
      been treated with systemic chemotherapy (breast, n = 141, age = 57.0 +/- 10.1
      years; lymphoma, n = 66, age = 55.8 +/- 13.5 years) or local therapy only
      (breast, n = 294, age = 65.8 +/- 9.1 years; lymphoma, n = 37, age = 50.4 +/- 12.8
      years) were interviewed by phone using the Quality of Life-Cancer Survivors Tool.
      RESULTS: Multivariate analysis of covariance, controlling for sex, age,
      education, stage of disease, and time since last treatment, revealed that
      survivors who had been treated with systemic chemotherapy scored significantly
      lower on overall QOL compared with survivors treated with local therapy only (P =
      .04). Analysis of covariance on the subscale scores revealed that, compared with
      survivors who received local therapy, survivors treated with chemotherapy scored
      significantly lower on the Social subscale (P < .0001), but no differences
      emerged on the Psychological or Spiritual subscales. There was a statistically
      significant interaction between treatment and diagnosis (P = .01), as measured by
      the Physical subscale, indicating that lymphoma survivors treated with
      chemotherapy scored worse than all other groups. CONCLUSION: Important QOL
      differences emerged between the chemotherapy and local therapy groups, suggesting
      that long-term QOL may vary depending on the type of treatment and diagnosis.

PMID- 15994150
TI  - Outcome of cancer patients considered for intensive care unit admission: a
      hospital-wide prospective study.
AB  - PURPOSE: To evaluate the outcome of cancer patients considered for admission to
      the intensive care unit (ICU). PATIENTS AND METHODS: Prospective, one-year
      hospital-wide study of all cancer and hematology patients, including bone marrow
      transplantation patients, for whom admission to the ICU was requested. RESULTS:
      Of the 206 patients considered for ICU admission, 105 patients (51%) were
      admitted. Of the 101 patients who were not admitted, 54 patients (26.2%) were
      considered too sick to benefit, and 47 patients (22.8%) were considered to be too
      well to benefit from the ICU. Of these 47 patients, 13 patients were admitted
      later. Survival rates after 30 and 180 days were significantly associated with
      admission status (P < .0001). Remission of the malignancy (odds ratio [OR], 3.37;
      95% CI, 1.25 to 9.07) was independently associated with ICU admission, whereas
      poor chronic health status (OR, 0.38; 95% CI, 0.16 to 0.74) and solid tumor (OR,
      0.43; 95% CI, 0.24 to 0.78) were associated with ICU refusal. In admitted
      patients, 30-day and 6-month survival rates were 54.3% and 32.4%, respectively.
      Of the patients considered too sick to benefit from ICU admission, 26% were alive
      on day 30 and 16.7% on day 180. Among patients considered too well to benefit,
      the 30-day survival rate was a worrisome 78.7%. Calibration of the Mortality
      Probability Model (the only score available at triage) was of limited value for
      predicting 30-day survival (area under the curve, 0.62). CONCLUSION: Both the
      excess mortality in too-well patients later admitted to the ICU and the
      relatively good survival in too-sick patients suggest the need for a broader
      admission policy.

PMID- 15994151
TI  - Persistence of medical change at implementation of clinical guidelines on medical
      practice: a controlled study in a cancer network.
AB  - PURPOSE: A cancer network of general or private hospitals of a French region was
      started in 1995 for improving quality of care and rationalizing medical
      prescriptions. The impact of implementing a clinical practice guidelines (CPG)
      project assessed conformity with guidelines in medical practice; significant
      changes were observed within the network, whereas no changes were observed in a
      control region without cancer network. In the present study, we evaluated the
      persistence of conformity to guidelines through a new medical audit. PATIENTS AND
      METHODS: In 1999, the hospitals of the previously compared experimental and
      control groups accepted to reassess the impact of CPG. A controlled transversal
      study was performed in the experimental group (cancer network) and in the control
      group (no regional cancer network). In 1996 (first audit) and in 1999 (present
      audit), all new patients with colon cancer (177 and 200 in experimental group and
      118 and 100 in control group, respectively) and early breast cancer (444 and 381
      in experimental group and 172 and 204 in control group, respectively) were
      selected. RESULTS: In the experimental group, the compliance of medical decisions
      with CPG was significantly higher in 1999 than in 1996 for colon cancer (73%; 95%
      CI, 67% to 79% v 56%; 95% CI, 49% to 63%, respectively; P = .003) and similar for
      the two periods for breast cancer (36%; 95% CI, 31% to 41% v 40%; 95% CI, 35% to
      44%, respectively; P = .24). In the control group, compliance was significantly
      higher in 1999 than in 1996 for colon cancer (67%; 95% CI, 58% to 76% v 38%; 95%
      CI, 29% to 47%, respectively; P < .001) and identical for the two periods for
      breast cancer (4%; 95% CI, 1% to 7% v 7%; 95% CI, 3% to 11%, respectively; P =
      .19). CONCLUSION: The CPG program for cancer management produced persistent
      changes in medical practice in our cancer network in terms of conformity with
      CPG.

PMID- 15994152
TI  - Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis and
      cutaneous toxicity of the hand.
AB  - PURPOSE: Onycholysis and skin toxicity occur in approximately 30% of patients
      treated with docetaxel. We investigated the efficacy and safety of an Elasto-Gel
      (84400 APT Cedex, Akromed, France) frozen glove (FG) for the prevention of
      docetaxel-induced onycholysis and skin toxicity. PATIENTS AND METHODS: Patients
      receiving docetaxel 75 mg/m2 alone or in combination chemotherapy were eligible
      for this case-control study. Each patient wore an FG for a total of 90 minutes on
      the right hand. The left hand was not protected and acted as the control.
      Onycholysis and skin toxicity were assessed at each cycle by National Cancer
      Institute Common Toxicity Criteria and documented by photography. Wilcoxon
      matched-pairs rank test was used. RESULTS: Between August 2002 and September
      2003, 45 patients were evaluated. Onycholysis and skin toxicity were
      significantly lower in the FG-protected hand compared with the control hand (P =
      .0001). Onycholysis was grade (G) 0 in 89% v 49% and G1 to 2 in 11% v 51% for the
      FG-protected hand and the control hand, respectively. Skin toxicity was G0 in 73%
      v 41% and G1 to 2 in 27% v 59% for the FG-protected and the control hand,
      respectively. Median time to nail and skin toxicity occurrence was not
      significantly different between the FG-protected and the control hand,
      respectively (106 v 58 days for nail toxicity; 57 v 58 days for skin toxicity).
      Five patients (11%) experienced discomfort due to cold intolerance. CONCLUSION:
      FG significantly reduces the nail and skin toxicity associated with docetaxel and
      provides a new tool in supportive care management to improve a patient's quality
      of life.

PMID- 15994153
TI  - Effects of 9-cis-retinoic acid on the insulin-like growth factor axis in former
      smokers.
AB  - PURPOSE: Insulin-like growth factor (IGF) axis has been associated with the risk
      of lung cancer. 9-cis-retinoic acid (9-cis-RA) has shown potential
      chemopreventive activities in former smokers. This study was designed to evaluate
      the effects of 9-cis-RA on IGF axis in former smokers to identify any benefit the
      retinoid may have in preventing lung cancer. PATIENTS AND METHODS: Serum
      concentrations of IGF-I, IGF binding protein (IGFBP)-3, and their molar ratio
      (IGF-I/IGFBP-3) were measured with radioimmunoassay kits in stored blood samples
      from the participants of an original chemoprevention trial. The participants had
      ceased smoking for at least 12 months and were randomly assigned to receive 3
      months of daily oral 9-cis-RA (100 mg) or placebo. All statistical tests were two
      sided. RESULTS: A total of 111 samples from the study's baseline and 84 samples
      from the 3 months treatment were analyzed. The serum concentrations of IGF-I and
      IGF-I/IGFBP-3 at baseline were significantly lower in female than in male
      participants. After 3 months of treatment, the serum level of IGF-I and IGF
      I/IGFBP-3 were significantly lower in the 9-cis-RA group than in the placebo
      group (P = .03 and P < .01, respectively), but the IGFBP-3 level was
      significantly higher (P = .03). CONCLUSION: 9-cis-RA treatment modulated the IGF
      axis in former smokers, suggesting that the IGF axis is a potential target for
      the chemopreventive activities of 9-cis-RA and that the serum concentrations of
      IGF, IGFBP-3, and IGF-I/IGFBP-3 could serve as surrogate end point biomarkers of
      9-cis-RA treatment.

PMID- 15994154
TI  - Randomized phase II designs in cancer clinical trials: current status and future
      directions.
AB  - PURPOSE: Randomized phase II (RPh2) designs are popular in cancer clinical trials
      because of the smaller sample size requirements when multiple treatments are
      being evaluated. We reviewed the use of RPh2 designs and give comments on future
      directions. DESIGN: The trial design, statistical properties, conduct, data
      analysis, results, and reporting were examined in RPh2 trials reported from 1986
      to 2002. RESULTS: A statistical design was reported in only 46% of the 266 cancer
      trials, and approximately half of those provided inadequate information. Most
      studies applied randomization to achieve patient comparability, while embedding a
      one-sample phase II design within each treatment arm. Seventy-five percent of the
      trials' accruals were within +/- 10% of their targets. The average accrual rate
      was 3.3 patients per month. Planned interim analyses were reported in 27% of the
      trials, and 56% of the trials were stopped early; 69%, 13%, 13%, and 4% of the
      trial discontinuations were because of lack of efficacy, efficacy, toxicity, and
      slow accrual, respectively. Thirty-nine trials (14%) recommended or started phase
      III evaluations, with four positive reports in six phase III studies identified.
      CONCLUSION: There is a trend of increasing use of RPh2 designs in cancer
      research. Continued improvement in study design, conduct, analysis, and reporting
      is required to enhance the quality of RPh2 designs. The accrual rate and success
      rate of the trials remain low, and therefore, futility stopping rules to
      terminate ineffective treatment arm(s) should be implemented more frequently.
      More innovative, flexible RPh2 designs are needed to facilitate the development
      of effective cancer treatments.

PMID- 15994155
TI  - Patients with unusual bladder malignancies and a rare cause of splenomegaly. Case
      1. Small-cell carcinoma of the urinary bladder.

PMID- 15994156
TI  - Patients with unusual bladder malignancies and a rare cause of splenomegaly. Case
      2. Rhabdomyosarcoma of the urinary bladder in an adult.

PMID- 15994157
TI  - Patients with unusual bladder malignancies and a rare cause of splenomegaly. Case
      3. Littoral cell angioma of the spleen in a patient with previous lymphoma.

PMID- 15994158
TI  - Talking to a patient.

PMID- 15994159
TI  - Comment on "Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized,
      placebo-controlled, double-blind trial from the ORN96 Study Group".

PMID- 15994160
TI  - Hyperbaric oxygen therapy for radionecrosis: clear advice from confusing data.

PMID- 15994162
TI  - Withholding information from study participants in clinical trials: ethical
      considerations.

PMID- 15994163
TI  - Challenge in the treatment of estrogen-receptor-negative ductal carcinoma in
      situ.

PMID- 15994166
TI  - Internet-based approach to multi-institutional patient recruitment in the medico
      legal age.

PMID- 15994165
TI  - Regression of low-grade non-Hodgkin's lymphoma after treatment with pegylated
      interferon plus ribavirin in hepatitis C virus infection.

PMID- 15994168
TI  - Successful use of haploidentical stem-cell transplantation with KIR mismatch as
      initial therapy for poor-risk myelodysplastic syndrome.

PMID- 15994170
TI  - Assisted hospital discharge in patients with chronic respiratory disorders.

PMID- 15994171
TI  - Difficult patients or difficult encounters?

PMID- 15994172
TI  - Bigger picture, lighter touch.

PMID- 15994173
TI  - Small fitness effect of mutations in highly conserved non-coding regions.
AB  - Comparison of human and mouse genomes has revealed that many non-coding regions
      have levels of sequence conservation similar to protein-coding genes. These
      regions have attracted a lot of attention as potentially functional genomic
      sequences. However, little is known about the effect mutations in these conserved
      non-coding regions have on fitness and how many of them are present in the human
      genome as deleterious polymorphisms. To gain insight into the selective
      constraints imposed on conserved non-coding and protein-coding regions, we
      compared substitution rates in primate and rodent lineages and analyzed the
      density and allele frequencies of human polymorphism. Genomic regions conserved
      between primate and rodent groups show higher relative conservation within
      rodents than within primates. Thus, our analysis indicates a genome-wide
      relaxation of selective constraint in the primate lineage, which most likely
      resulted from a smaller effective population size. We found that this relaxation
      is much more profound in conserved non-coding regions than in protein-coding
      regions, and that mutations at a large proportion of sites in conserved non
      coding regions are associated with very small fitness effect. Data on human
      polymorphism are also consistent with very weak selection in conserved non-coding
      regions. This staggering enrichment in sites at the borderline of neutrality can
      be explained by assuming an important role for synergistic epistasis in the
      evolution of non-coding regions. Our results suggest that most individual
      mutations in conserved non-coding regions are only slightly deleterious but are
      numerous and may have a significant cumulative impact on fitness.

PMID- 15994175
TI  - What is the impact of sentinel node biopsy in the management of cancer?

PMID- 15994174
TI  - A previously unidentified amino-terminal domain regulates transcriptional
      activity of wild-type and disease-associated human GLI2.
AB  - Zinc finger-containing Gli proteins mediate responsiveness to Hedgehog (Hh)
      signaling, with Gli2 acting as the major transcriptional activator in this
      pathway in mice. The discovery of disease-associated mutations points to a
      critical role for GLI2 in human Hh signaling as well. Here, we show that human
      GLI2 contains previously undescribed 5' sequence, extending the amino-terminus an
      additional 328 amino acids. In vitro, transcriptional activity of full-length
      GLI2 is up to 30 times lower than that of GLI2DeltaN (previously thought to
      represent the entire GLI2 protein), revealing the presence of an amino-terminal
      repressor domain in the full-length protein. GLI2DeltaN also exhibits potent
      transcriptional activity in vivo: overexpression in mouse skin leads to the
      formation of Hh-independent epithelial downgrowths resembling basal cell
      carcinomas, which in humans are associated with constitutive Hh signaling. The
      discovery of this additional, functionally relevant GLI2 sequence led us to re
      examine several pathogenic human GLI2 mutants, now containing the entire amino
      terminal domain. On the basis of the functional domains affected by the
      mutations, mutant GLI2 proteins exhibited either loss-of-function or dominant
      negative activity. Moreover, deletion of the amino-terminus abrogated dominant
      negative activity of mutant GLI2, revealing that this domain is required for
      transcriptional repressor activity of pathogenic GLI2. Our results establish the
      presence of an amino-terminal transcriptional repressor domain that plays a
      critical role in modulating the function of wild-type GLI2 and is essential for
      dominant-negative activity of a GLI2 mutant associated with human disease.

PMID- 15994176
TI  - Dose-finding study of weekly docetaxel, anthracyclines plus fluoropyrimidines as
      first-line treatment in advanced breast cancer.
AB  - BACKGROUND: The efficacy and safety of prolonged fluoropyrimidines, either
      intravenously or orally, prompted their integration with taxanes and
      anthracyclines in the treatment of advanced breast cancer (ABC). We conducted
      three subsequent dose-finding studies on first-line chemotherapy in ABC with
      anthracyclines, either epirubicin (E) or doxorubicin (A), and docetaxel (T), both
      given on days 1 and 8 every 3 weeks, plus continuous infusion (CI) 5-fluorouracil
      (F) or capecitabine (X). PATIENTS AND METHODS: Sixty-two patients (37% dominant
      visceral disease, 48% locally advanced disease, 45% two or more sites involved),
      received different doses of T (60--80 mg/m(2)), A (40--50 mg/m(2)) or E (60--90
      mg/m(2)) and X (1,650 and 2,000 mg/m(2)), or CI F at a fixed daily dose of 200
      mg/m(2). Cardiac function was monitored at baseline and then every four cycles by
      echocardiography. RESULTS: The median number of cycles per patient with all
      regimens was four (range one to eight). Haematological and gastrointestinal
      toxicity defined the maximum tolerated doses, at T-80/E-90 mg/m(2) with TEF, T
      70/A50/X-2,000 mg/m(2) with TAX and T-70/E-80/X-1,650 mg/m(2) with TEX. Two
      patients treated with TEF developed transient cardiac toxicity (dilatative
      cardiomyopathy and coronary subtotal stenosis requiring stenting) after
      cumulative E doses of 400 mg and 1,100 mg/m(2), respectively. Fifty-nine patients
      were evaluable for response; the overall response rates (ORR) were comparable
      between regimens (54% with TEF, 71% with TAX and 86% with TEX), with an 81% ORR
      in 31 patients with locally advanced disease. CONCLUSIONS: The addition of
      fluoropyrimidines to weekly, intermittent ET is well tolerated and active in ABC.

PMID- 15994177
TI  - Plasticity in the positive selection of T cells: affinity of the selecting
      antigen and IL-7 affect T cell responsiveness.
AB  - The current study examines how responsiveness of T cells is affected by the
      avidity of the peptide/MHC engaged during positive selection of their thymocyte
      precursors. We used a thymus reaggregate culture system in which CD4(+)CD8(+)
      thymocytes from AND TCR transgenic mice were induced to undergo positive
      selection by pigeon cytochrome c (PCC) peptide or its analogs presented by I-E(k)
      class II MHC on a thymic epithelial cell line. When low-affinity peptide analogs
      drove positive selection, up to 100 microM was needed to produce >50% CD4(+) T
      cells, and these cells were highly responsive to PCC. In contrast, <0.2 microM
      high-affinity peptides was required to achieve similar selection efficiency, but
      the resultant cells failed to respond to PCC. However, these cells were not dead
      based on dye exclusion and capacity to respond to phorbal ester and to agonist if
      IL-2 was also present, supporting the view that non-responsiveness of cells
      selected on high-affinity peptides is a form of central T cell tolerance distinct
      from deletion. Cells selected on intermediate-affinity peptides showed variable
      responsiveness which was suppressed 5- to 10-fold by addition during reaggregate
      culture of antibody to the IL-7R. Similarly, supplementary IL-7 in the
      reaggregate culture produced CD4(+) T cells that were promiscuously responsive.
      Overall, this study demonstrates that the responsiveness of T cells is not
      rigidly controlled and that the presence of IL-7 during T cell development has
      the potential to negate central T cell tolerance and produce autoreactive T
      cells.

PMID- 15994178
TI  - Serotonergic neurones drive spontaneous activity in the developing mouse
      hindbrain.

PMID- 15994179
TI  - Found in translation: neural feedback from exercising muscles.

PMID- 15994181
TI  - Opsin activation of transduction in the rods of dark-reared Rpe65 knockout mice.
AB  - Rpe65 knockout mice (Rpe65-/-) are unable to synthesize the visual pigment
      chromophore 11-cis retinal; however, if these animals are reared in complete
      darkness, the rod photoreceptors accumulate a small amount of 9-cis retinal and
      its corresponding visual pigment isorhodopsin. Suction-electrode recording of
      single rods from dark-reared Rpe65-/- mice showed that the rods were about 400
      times less sensitive than wild-type control rods and that the maximum responses
      were much smaller in amplitude. Spectral sensitivity measurements indicated that
      Rpe65-/- rod responses were generated by isorhodopsin rather than rhodopsin.
      Sensitivity and pigment concentration were compared in the same mice by measuring
      light responses from rods of one eye and pigment concentration from the retina of
      the other eye. Retinas had 11-35% of the normal pigment level, but the rods were
      of the order of 20-30 times less sensitive than could be accounted for by the
      loss in quantum catch. This extra desensitization must be caused by opsin
      dependent activation of the visual cascade, which leads to a state equivalent to
      light adaptation in the dark-adapted rod. By comparing the sensitivity of dark
      reared Rpe65-/- rods to that produced in normal rods by background light, we
      estimate that Rpe65-/- opsin is of the order of 2.5x10(-5) as efficient in
      activating transduction as photoactivated rhodopsin (Rh*) in WT mice. Dark-reared
      Rpe65-/- rods are less desensitized than rods from cyclic light-reared Rpe65-/-
      mice, have about 50% more photocurrent and degenerate at a slower rate. Retinas
      sectioned after 9 months in darkness show a larger number of photoreceptor nuclei
      in dark-reared animals than in cyclic light-reared animals, though both have
      fewer nuclei than in cyclic light-reared wild-type retinas. Both also have
      shorter outer segments and a lower free-Ca2+ concentration. These experiments
      provide the first quantitative measurement of opsin activation in physiologically
      responding mammalian rods.

PMID- 15994182
TI  - Beyond the brush border: NHERF4 blazes new NHERF turf.
AB  - The Na exchanger regulatory factor (NHERF) family of epithelial-enriched PDZ
      domain scaffolding proteins plays important roles in maintaining and regulating
      epithelial cell function. The NHERFs exhibit some overlap in tissue distribution
      and binding partners, suggesting redundant functions. Yet, it is clear that each
      NHERF protein exhibits distinct properties, translating into unique cellular
      functions. The work summarized in this review suggests the most recently
      identified family member, NHERF4, is the most divergent. Additional investigation
      is needed, however, to understand more completely the role of NHERF4 in the
      context of the NHERF family.

PMID- 15994183
TI  - Nitric oxide synthase inhibition affects sarcoplasmic reticulum Ca2+ release in
      skeletal muscle fibres from mouse.
AB  - Nitric oxide (NO) generated by skeletal muscle is believed to regulate force
      production but how this is achieved remains poorly understood. In the present
      work we tested the effects of NO synthase (NOs) inhibitors on membrane current
      and intracellular calcium in isolated skeletal muscle fibres from mouse, under
      voltage-clamp conditions. Resting [Ca(2+)] and [Ca(2+)] transients evoked by
      large depolarizations exhibited similar properties in control fibres and in
      fibres loaded with tenth millimolar levels of the NOs inhibitor N-nitro-L
      arginine (L-NNA). Yet the voltage dependence of calcium release was found to be
      shifted by approximately 15 mV towards negative values in the presence of L-NNA.
      This effect could be reproduced by the other NOs inhibitor S-methyl-L
      thiocitrulline (L-SMT). Separate experiments showed that the voltage dependence
      of charge movement and of the slow calcium current were unaffected by the
      presence of L-NNA, ruling out an effect on the voltage sensor. A negative shift
      in the voltage dependence of calcium release with no concurrent alteration in the
      properties of charge movement was also observed in fibres exposed to the oxidant
      H(2)O(2) (1 mM). Conversely the reducing agent dithiothreitol (10 mM) had no
      obvious effect on Ca(2+) release. Overall, the results indicate that
      physiological levels of NO exert a tonic inhibitory control on the activation of
      the calcium release channels. Changes in the voltage dependence of Ca(2+) release
      activation may be a ubiquitous physiological consequence of redox-related
      modifications of the ryanodine receptor.

PMID- 15994184
TI  - cAMP increases Ca2+-dependent exocytosis through both PKA and Epac2 in mouse
      melanotrophs from pituitary tissue slices.
AB  - Cyclic AMP regulates Ca(2+)-dependent exocytosis through a classical protein
      kinase A (PKA)-dependent and an alternative cAMP-guanine nucleotide exchange
      factor (GEF)/Epac-dependent pathway in many secretory cells. Although increased
      cAMP is believed to double secretory output in isolated pituitary cells, the
      direct target(s) for cAMP action and a detailed and high-time resolved analysis
      of the effect of intracellular cAMP levels on the secretory activity in
      melanotrophs are still lacking. We investigated the effect of 200 microM cAMP on
      the kinetics of secretory vesicle depletion in mouse melanotrophs from fresh
      pituitary tissue slices. The whole-cell patch-clamp technique was used to
      depolarize melanotrophs and increase the cytosolic Ca(2+) concentration
      ([Ca(2+)](i)). Exogenous cAMP elicited an about twofold increase in cumulative
      membrane capacitance change and approximately 34% increase of high-voltage
      activated Ca(2+) channel amplitude. cAMP-dependent mechanisms did not affect
      [Ca(2+)](i), since the application of forskolin failed to change [Ca(2+)](i) in
      melanotrophs, a phenomenon readily observed in anterior lobe. Depolarization
      induced secretion resulted in two distinct kinetic components: a linear and a
      threshold component, both stimulated by cAMP. The linear component (ATP
      independent) probably represented the exocytosis of the release-ready vesicles,
      whereas the threshold component was assigned to the exocytosis of secretory
      vesicles that required ATP-dependent reaction(s) and > 800 nM [Ca(2+)](i). The
      linear component was modulated by 8-pCPT-2Me-cAMP (Epac agonist), while either H
      89 (PKA inhibitor) or Rp-cAMPS (the competitive antagonist of cAMP binding to
      PKA) completely prevented the action of cAMP on the threshold component. In line
      with this, 6-Phe-cAMP, (PKA agonist), increased the threshold component. From our
      study, we suggest that the stimulation of cAMP production by application of
      oestrogen, as found in pregnant mice, increases the efficacy of the hormonal
      output through both PKA and cAMP-GEFII/Epac2-dependent mechanisms.

PMID- 15994185
TI  - Arachidonate-regulated Ca2+-selective (ARC) channel activity is modulated by
      phosphorylation and involves an A-kinase anchoring protein.
AB  - In many non-excitable cells, the predominant mode of agonist-activated Ca(2+)
      entry switches from the arachidonic acid-regulated Ca(2+) (ARC) channels at low
      agonist concentrations, to store-operated channels at high concentrations.
      Underlying this process is the inhibition of the ARC channels by a calcineurin
      mediated dephosphorylation, which inhibits the ability of arachidonic acid to
      activate the channels. Following such a dephosphorylation, we found that
      restoration of the sensitivity of the ARC channels to arachidonic acid, as well
      as to low concentrations of carbachol, was specifically dependent on protein
      kinase A (PKA) activity. Inhibition of protein kinase C, protein kinase G or
      calmodulin-activated kinase had no effect. This action of PKA was unaffected by
      prolonged intracellular dialysis, whilst disruption of the binding of PKA to A
      kinase anchoring proteins (AKAPs) inhibited currents through ARC channels, and
      blocked the PKA-dependent effects. AKAP79, a protein which scaffolds both PKA and
      calcineurin, was shown to be present in the cells. These data illustrate the
      significance of PKA-dependent phosphorylation and calcineurin-dependent
      dephosphorylation in the overall regulation of ARC channel activity, and indicate
      the key role of an AKAP, possibly AKAP79, in the spatial organization these
      processes.

PMID- 15994186
TI  - The interstitial distribution of macromolecules in rat tumours is influenced by
      the negatively charged matrix components.
AB  - Knowledge of macromolecular distribution volumes is essential in understanding
      fluid transport within normal and pathological tissues. In this study in vivo we
      determined the distribution volumes of several macromolecules, including one
      monoclonal antibody, in tumours and tested whether charges associated with the
      tumour extracellular matrix influence their available volumes. Steady state
      levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI =
      7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were
      established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours
      by continuous infusion using osmotic minipumps. After a 5-7 day infusion period,
      the rats were nephrectomized and the extracellular volume was determined with
      51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum
      albumin or rat IgM in a separate series. Steady state concentrations of probes
      were determined in the interstitial fluid that was isolated by centrifugation
      from tumours or by post mortem wick implantation in the back skin. Calculations
      were made for interstitial fluid volume (Vi), along with the available (Va/Vi)
      and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the
      positively charged trastuzumab in tumours averaged 0.29 +/- 0.03 (n = 16), a
      value which was significantly lower than the corresponding one for IgG of 0.36 +/
      0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial
      fluid, whereas cationization of albumin reduced the excluded volume by
      approximately 50%. Our experiments suggest that the tumour interstitium acts as a
      negatively charged matrix and is an important factor in determining the
      macromolecular distribution volume.

PMID- 15994187
TI  - The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair
      cells through the mechano-electrical transducer channels.
AB  - The most serious side-effect of the widely used aminoglycoside antibiotics is
      irreversible intracellular damage to the auditory and vestibular hair cells of
      the inner ear. The mechanism of entry into the hair cells has not been
      unequivocally resolved. Here we report that extracellular dihydrostreptomycin not
      only blocks the mechano-electrical transducer channels of mouse outer hair cells
      at negative membrane potentials, as previously shown, but also enters the cells
      through these channels, which are located in the cells' mechanosensory hair
      bundles. The voltage-dependent blocking kinetics indicate an open-channel block
      mechanism, which can be well described by a two barrier-one binding site model,
      quantifying the antibiotic's block of the channel as well as its permeation in
      terms of the associated rate constants. The results identify the open transducer
      channels as the main route for aminoglycoside entry. Intracellularly applied
      dihydrostreptomycin also blocks the transducer channels, but at positive membrane
      potentials. However, the potency of the block was two orders of magnitude lower
      than that due to extracellular dihydrostreptomycin. Extracellular Ca2+ increases
      the free energy of the barrier nearest the extracellular side and of the binding
      site for dihydrostreptomycin. This reduces both the entry of dihydrostreptomycin
      into the channel and the channel's affinity for the drug. In vivo, where the
      extracellular Ca2+ concentration in the endolymph surrounding the hair bundles is
      < 100 microM, we predict that some 9000 dihydrostreptomycin molecules per second
      enter each hair cell at therapeutic drug concentrations.

PMID- 15994188
TI  - A heuristic approach for detecting RNA H-type pseudoknots.
AB  - MOTIVATION: RNA H-type pseudoknots are ubiquitous pseudoknots that are found in
      almost all classes of RNA and thought to play very important roles in a variety
      of biological processes. Detection of these RNA H-type pseudoknots can improve
      our understanding of RNA structures and their associated functions. However, the
      currently existing programs for detecting such RNA H-type pseudoknots are still
      time consuming and sometimes even ineffective. Therefore, efficient and effective
      tools for detecting the RNA H-type pseudoknots are needed. RESULTS: In this
      paper, we have adopted a heuristic approach to develop a novel tool, called
      HPknotter, for efficiently and accurately detecting H-type pseudoknots in an RNA
      sequence. In addition, we have demonstrated the applicability and effectiveness
      of HPknotter by testing on some sequences with known H-type pseudoknots. Our
      approach can be easily extended and applied to other classes of more general
      pseudoknots. AVAILABILITY: The web server of our HPknotter is available for
      online analysis at http://bioalgorithm.life.nctu.edu.tw/HPKNOTTER/ CONTACT:
      cllu@mail.nctu.edu.tw, chiu@cc.nctu.edu.tw

PMID- 15994189
TI  - Ontological analysis of gene expression data: current tools, limitations, and
      open problems.
AB  - Independent of the platform and the analysis methods used, the result of a
      microarray experiment is, in most cases, a list of differentially expressed
      genes. An automatic ontological analysis approach has been recently proposed to
      help with the biological interpretation of such results. Currently, this approach
      is the de facto standard for the secondary analysis of high throughput
      experiments and a large number of tools have been developed for this purpose. We
      present a detailed comparison of 14 such tools using the following criteria:
      scope of the analysis, visualization capabilities, statistical model(s) used,
      correction for multiple comparisons, reference microarrays available,
      installation issues and sources of annotation data. This detailed analysis of the
      capabilities of these tools will help researchers choose the most appropriate
      tool for a given type of analysis. More importantly, in spite of the fact that
      this type of analysis has been generally adopted, this approach has several
      important intrinsic drawbacks. These drawbacks are associated with all tools
      discussed and represent conceptual limitations of the current state-of-the-art in
      ontological analysis. We propose these as challenges for the next generation of
      secondary data analysis tools.

PMID- 15994190
TI  - The inference of protein-protein interactions by co-evolutionary analysis is
      improved by excluding the information about the phylogenetic relationships.
AB  - MOTIVATION: The prediction of protein-protein interactions is currently an
      important issue in bioinformatics. The mirror tree method uses evolutionary
      information to predict protein-protein interactions. However, it has been
      recognized that predictions by the mirror tree method lead to many false
      positives. The incentive of our study was to solve this problem by improving the
      method of extracting the co-evolutionary information regarding the protein pairs.
      RESULTS: We developed a novel method to predict protein-protein interactions from
      co-evolutionary information in the framework of the mirror tree method. The
      originality is the use of the projection operator to exclude the information
      about the phylogenetic relationships among the source organisms from the distance
      matrix. Each distance matrix was transformed into a vector for the operation. The
      vector is referred to as a 'phylogenetic vector'. We have proposed three ways to
      extract the phylogenetic information: (1) using the 16S rRNA from the same source
      organisms as the proteins under consideration, (2) averaging the phylogenetic
      vectors and (3) analyzing the principal components of the phylogenetic vectors.
      We examined the performance of the proposed methods to predict interacting
      protein pairs from Escherichia coli, using experimentally verified data. Our
      method was successful, and it drastically reduced the number of false positives
      in the prediction. AVAILABILITY: The R script for the prediction of protein
      protein interactions reported in this manuscript is available at
      http://timpani.genome.ad.jp/~proj/ CONTACT: sato@kuicr.kyoto-u.ac.jp
      SUPPLEMENTARY INFORMATION: The information is also available at the same site as
      the R script.

PMID- 15994191
TI  - TICO: a tool for improving predictions of prokaryotic translation initiation
      sites.
AB  - We provide the tool 'TICO' (Translation Initiation site COrrection) for improving
      the results of conventional gene finders for prokaryotic genomes with regard to
      exact localization of the translation initiation site (TIS). At the current state
      TICO provides an interface for direct post processing of the predictions obtained
      from the widely used program GLIMMER. Our program is based on a clustering
      algorithm for completely unsupervised scoring of potential TIS locations.
      AVAILABILITY: Our tool can be freely accessed through a web interface at
      http://tico.gobics.de/ CONTACT: maike@gobics.de

PMID- 15994192
TI  - MicroRNA identification based on sequence and structure alignment.
AB  - MOTIVATION: MicroRNAs (miRNA) are approximately 22 nt long non-coding RNAs that
      are derived from larger hairpin RNA precursors and play important regulatory
      roles in both animals and plants. The short length of the miRNA sequences and
      relatively low conservation of pre-miRNA sequences restrict the conventional
      sequence-alignment-based methods to finding only relatively close homologs. On
      the other hand, it has been reported that miRNA genes are more conserved in the
      secondary structure rather than in primary sequences. Therefore, secondary
      structural features should be more fully exploited in the homologue search for
      new miRNA genes. RESULTS: In this paper, we present a novel genome-wide
      computational approach to detect miRNAs in animals based on both sequence and
      structure alignment. Experiments show this approach has higher sensitivity and
      comparable specificity than other reported homologue searching methods. We
      applied this method on Anopheles gambiae and detected 59 new miRNA genes.
      AVAILABILITY: This program is available at
      http://bioinfo.au.tsinghua.edu.cn/miralign. SUPPLEMENTARY INFORMATION:
      Supplementary information is available at
      http://bioinfo.au.tsinghua.edu.cn/miralign/supplementary.htm.

PMID- 15994193
TI  - P-cats: prediction of catalytic residues in proteins from their tertiary
      structures.
AB  - P-cats is a web server that predicts the catalytic residues in proteins from the
      atomic coordinates. P-cats receives a coordinate file of the tertiary structure
      and sends out analytical results via e-mail. The reply contains a summary and two
      URLs to allow the user to examine the conserved residues: one for interactive
      images of the prediction results and the other for a graphical view of the
      multiple sequence alignment. AVAILABILITY: P-cats is freely available at http://p
      cats.hgc.jp/p-cats CONTACT: kino@ims.u-tokyo.ac.jp

PMID- 15994194
TI  - TO-GO: a Java-based Gene Ontology navigation environment.
AB  - TO-GO is a Gene Ontology (GO) navigation tool, which is implemented as a Java
      application. After the initial data downloading, the GO term tree can be
      interactively navigated without further network transfer. Local annotation can be
      incorporated. It supports querying by GO terms or associated gene product
      information, displaying the result as a table or a sub-tree. The result from the
      search for a set of external database accessions includes the number of gene
      products associated with each node, inclusive of sub-nodes. Search results can be
      further processed by set operations and these set operations can be quite useful
      for expression profile data analysis. A copy/paste function is also implemented
      in order to facilitate data exchange between applications. AVAILABILITY: TO-GO is
      freely available at http://www.ngic.re.kr/togo/index.html CONTACT:
      ungsik@kribb.re.kr

PMID- 15994195
TI  - GeneInfoMiner--a web server for exploring biomedical literature using batch
      sequence ID.
AB  - GeneInfoMiner is a web-based system for searching Medline abstracts using
      sequence ID lists such as GenBank accession numbers derived from high-throughput
      experiments. It will map query results to MeSH topics to facilitate the
      exploration of the biological significance of the sequence ID lists.
      GeneInfoMiner is based on a custom gene and protein name identification engine
      that can map gene and protein names to important molecular biology databases.

PMID- 15994196
TI  - SynBrowse: a synteny browser for comparative sequence analysis.
AB  - MOTIVATION: The recent efforts of various sequence projects to sequence deeply
      into various phylogenies provide great resources for comparative sequence
      analysis. A generic and portable tool is essential for scientists to visualize
      and analyze sequence comparisons. RESULTS: We have developed SynBrowse, a synteny
      browser for visualizing and analyzing genome alignments both within and between
      species. It is intended to help scientists study macrosynteny, microsynteny and
      homologous genes between sequences. It can also aid with the identification of
      uncharacterized genes, putative regulatory elements and novel structural features
      of a species. SynBrowse is a GBrowse (the Generic Genome Browser) family software
      tool that runs on top of the open source BioPerl modules. It consists of two
      components: a web-based front end and a set of relational database back ends.
      Each database stores pre-computed alignments from a focus sequence to reference
      sequences in addition to the genome annotations of the focus sequence. The user
      interface lets end users select a key comparative alignment type and search for
      syntenic blocks between two sequences and zoom in to view the relationships among
      the corresponding genome annotations in detail. SynBrowse is portable with simple
      installation, flexible configuration, convenient data input and easy integration
      with other components of a model organism system. AVAILABILITY: The software is
      available at http://www.gmod.org CONTACT: vbrendel@iastate.edu

PMID- 15994197
TI  - Emx2 regulates mammalian reproduction by altering endometrial cell proliferation.
AB  - The molecular mechanisms that underlie embryo implantation are poorly understood.
      Under the control of sex steroids, uterine endometrium undergoes tremendous, yet
      tightly controlled, proliferation in each estrous cycle to facilitate
      implantation; disorders of endometrial proliferation underlie several uterine
      diseases. We have previously identified the Emx2 gene as a transcriptional target
      of HOXA10 regulation in the reproductive tract. Here we report the function of
      Emx2 in murine implantation and regulation of endometrial proliferation. We
      transfected mice on d 2 post coitus with pcDNA3.1/Emx2, Emx2 antisense, or
      respective controls consisting of empty pcDNA3.1 or a random order
      oligonucleotide by intrauterine lipofection. Increased expression of Emx2 reduced
      average implantation rate by approximately 40% (P = 0.00006) resulting in an
      average number of implanted embryos per litter of 13.7 in the control group to
      8.2 in the pcDNA3.1/Emx2-treated group. Neither treatment altered the number of
      mice attaining pregnancy with at least one embryo. Decreased Emx2 expression did
      not alter litter size. Neither treatment affected the birth weight of the pups.
      To elucidate potential mechanisms through which Emx2-regulated reproduction,
      markers of endometrial differentiation, proliferation, and apoptosis were
      assessed. Increased Emx2 expression significantly decreased endometrial cell
      proliferating cell nuclear antigen expression and 5'-bromo-2' deoxyuridine
      incorporation. Markers of stromal cell differentiation (IGF binding protein-1,
      prolactin), epithelial differentiation (calcitonin), and apoptosis (activated
      caspase3) were unchanged. In human endometrial epithelial cells in vitro, Emx2
      reduced cell number indicating diminished proliferation. Emx2 controls mammalian
      reproduction by adjusting endometrial cell proliferation without effecting
      differentiation. Regulated uterine Emx2 expression is necessary during
      reproduction for maximal implantation and litter size.

PMID- 15994199
TI  - The N-terminal juxtamembrane segment of the V1a vasopressin receptor provides two
      independent epitopes required for high-affinity agonist binding and signaling.
AB  - It is fundamentally important to define how agonist-receptor interaction differs
      from antagonist-receptor interaction. The V1a vasopressin receptor (V1aR) is a
      member of the neurohypophysial hormone subfamily of G protein-coupled receptors.
      Using alanine-scanning mutagenesis of the N-terminal juxtamembrane segment of the
      V1aR, we now establish that Glu54 (1.35) is critical for arginine vasopressin
      binding. The mutant [E54A]V1aR exhibited decreased arginine vasopressin affinity
      (1700-fold) and disrupted signaling, but antagonist binding was unaffected.
      Mutation of Glu54 had an almost identical pharmacological effect as mutation of
      Arg46, raising the possibility that agonist binding required a mutual interaction
      between Glu54 and Arg46. The role of these two charged residues was investigated
      by 1) substituting Glu54; 2) inserting additional Glu/Arg in transmembrane helix
      (TM) 1; 3) repositioning the Glu/Arg in TM1; and 4) characterizing the reciprocal
      mutant [R46E/E54R]V1aR. We conclude that 1) the positive/negative charges need to
      be precisely positioned in this N terminus/TM1 segment; and 2) Glu54 and Arg46
      function independently, providing two discrete epitopes required for high
      affinity agonist binding and signaling. This study explains why Glu and Arg, part
      of an -R(X3)L/V(X3)E(X3)L- motif, are conserved at these loci throughout this G
      protein-coupled receptor subfamily and provides molecular insight into key
      differences between agonist and antagonist binding requirements.

PMID- 15994198
TI  - The protein kinase C pathway acts through multiple transcription factors to
      repress gonadotropin-releasing hormone gene expression in hypothalamic GT1-7
      neuronal cells.
AB  - The GnRH gene uses two well-defined regions to target expression to a small
      population of hypothalamic GnRH neurons: a 173-bp proximal promoter and a 300-bp
      enhancer localized at approximately -1800 to -1500 bp from the start site.
      Interaction of multiple factors with the GnRH enhancer and promoter is required
      to confer neuron-specific expression in vivo and in cells in culture. In
      addition, the expression of the GnRH gene is regulated by numerous
      neurotransmitters and hormones. Several of these effectors act through membrane
      receptors to trigger the protein kinase C pathway, and 12-O-tetradecanoyl phorbol
      13-acetate (TPA), a modulator of this pathway, has been shown to suppress GnRH
      gene expression through the promoter. We find that TPA suppresses expression
      through the GnRH enhancer as well as the promoter. In the enhancer, an Oct-1
      binding site, a Pbx/Prep binding site, Msx/Dlx binding sites, and a previously
      unidentified protein-binding element at -1793, all contribute to TPA suppression.
      TPA treatment leads to decreased binding of Oct-1 and Pbx1a/Prep to their sites.
      However, a complex formed by GT1-7 nuclear extracts on the -1793 site is not
      affected by TPA treatment. It is known that cooperative interaction among
      multiple factors is necessary for GnRH gene expression; thus, one mechanism by
      which TPA suppresses GnRH gene expression is to disengage some of these factors
      from their cis-regulatory elements.

PMID- 15994200
TI  - Regulation of protein kinase B tyrosine phosphorylation by thyroid-specific
      oncogenic RET/PTC kinases.
AB  - Papillary thyroid carcinoma (PTC) is a heterogenous disorder characterized by
      unique gene rearrangements and gene mutations that activate signaling pathways
      responsible for cellular transformation, survival, and antiapoptosis. Activation
      of protein kinase B (PKB) and its downstream signaling pathways appears to be an
      important event in thyroid tumorigenesis. In this study, we found that the
      thyroid-specific oncogenic RET/PTC tyrosine kinase is able to phosphorylate PKB
      in vitro and in vivo. RET/PTC-transfected cells showed tyrosine phosphorylation
      of endogenous and exogenous PKB, which was independent of phosphorylation of T308
      and S473 regulated by the upstream kinases phosphoinositide-dependent kinase-1
      and -2, respectively. The PKB Y315 residue, which is known to be phosphorylated
      by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC.
      RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase
      activity. The activation of PKB by RET/PTC blocked the activity of the forkhead
      transcription factor, FKHRL1, but a Y315F mutant of PKB failed to inhibit FKHRL1
      activity. In summary, these observations suggest that RET/PTC is able to
      phosphorylate the Y315 residue of PKB, an event that results in maximal
      activation of PKB for RET/PTC-induced thyroid tumorigenesis.

PMID- 15994201
TI  - Possible role of 5'-adenosine triphosphate in synchronization of Ca2+
      oscillations in primate luteinizing hormone-releasing hormone neurons.
AB  - LHRH neurons derived from the olfactory placode region of monkey embryos exhibit
      spontaneous intracellular Ca2+ ([Ca2+]i) oscillations that synchronize among LHRH
      neurons and nonneuronal cells at a frequency similar to pulsatile LHRH release.
      To understand the mechanism of intercellular communication between LHRH neurons
      and nonneuronal cells, which leads to synchronization, we examined the possible
      role of ATP. 1) ATP, not ADP or AMP, stimulated both LHRH release and [Ca2+]i
      concentration, whereas the ATP-induced [Ca2+]i response was abolished by infusion
      of apyrase, which hydrolyzes ATP; 2) the ATP-induced [Ca2+]i response occurred in
      normal (but not low) extracellular Ca2+ and was blocked by the voltage-dependent
      L-type Ca2+ channel blocker, nifedipine; 3) pharmacological experiments with
      purinergic receptor agonists and antagonists indicated that the ATP-induced
      [Ca2+]i response in LHRH neurons was mediated through P2X, but not P2Y,
      receptors; 4) cloning and sequencing studies suggested that P2X2 and P2X4
      transcripts were present in olfactory placode cultures; and 5) P2X2 receptors and
      P2X4 were expressed in LHRH neurons. The results suggest that ATP may play a role
      in intercellular communication when LHRH neurons synchronize, and raise the
      possibility that nonneuronal cells, such as glia, may be a crucial component of
      the in vivo LHRH neurosecretory system.

PMID- 15994202
TI  - Ventromedial hypothalamic nucleus-specific enhancer of Ad4BP/SF-1 gene.
AB  - Ad4BP/SF-1 [Ad4 binding protein/steroidogenic factor-1 (designated NR5A1)] is a
      transcription factor essential for animal reproduction. Based on the phenotypes
      observed in gene-disrupted mice, Ad4BP/SF-1 is thought to be involved in
      establishment of the hypothalamic-pituitary-gonadal axis. However, the mechanisms
      underlying tissue-specific expression of Ad4BP/SF-1 are largely unknown. Here, we
      investigated the cis-regulatory regions of the mouse Ad4BP/SF-1 gene by
      transgenic mouse assays, and identified a ventromedial hypothalamic nucleus (VMH)
      specific enhancer. The enhancer localized in intron 6 is highly conserved between
      mouse, human, and chick. The enhancer has the potential to reproduce endogenous
      gene expression from the fetal ventromedial diencephalon to the adult VMH. The
      VMH enhancer was characterized by the presence of suppressive and activating
      elements. Mutation of the former element resulted in ectopic lacZ reporter gene
      expression in an area dorsal to the intrinsic expression domain and in the
      ventricular zone, whereas mutations in the latter containing ATTA motifs led to
      the disappearance of the reporter gene expression, suggesting the involvement of
      homeobox proteins. Using nuclear extracts prepared from the adult hypothalami,
      EMSAs identified specific protein binding to the activating elements but not to
      the suppressive element.

PMID- 15994203
TI  - G protein-coupled receptor kinase 2 mediates endothelin-1-induced insulin
      resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1
      pathways in 3T3-L1 adipocytes.
AB  - G protein-coupled receptor kinases (GRKs) regulate seven-transmembrane receptors
      (7TMRs) by phosphorylating agonist-activated 7TMRs. Recently, we have reported
      that GRK2 can function as a negative regulator of insulin action by interfering
      with G protein-q/11 alpha-subunit (Galphaq/11) signaling, causing decreased
      glucose transporter 4 (GLUT4) translocation. We have also reported that chronic
      endothelin-1 (ET-1) treatment leads to heterologous desensitization of insulin
      signaling with decreased tyrosine phosphorylation of insulin receptor substrate
      (IRS)-1 and Galphaq/11, and decreased insulin-stimulated glucose transport in 3T3
      L1 adipocytes. In the current study, we have investigated the role of GRK2 in
      chronic ET-1-induced insulin resistance. Insulin-induced GLUT4 translocation was
      inhibited by pretreatment with ET-1 for 24 h, and we found that this inhibitory
      effect was rescued by microinjection of anti-GRK2 antibody or GRK2 short
      interfering RNA. We further found that GRK2 mediates the inhibitory effects of ET
      1 by two distinct mechanisms. Firstly, adenovirus-mediated overexpression of
      either wild-type (WT)- or kinase-deficient (KD)-GRK2 inhibited Galphaq/11
      signaling, including tyrosine phosphorylation of Galphaq/11 and cdc42-associated
      phosphatidylinositol 3-kinase activity. Secondly, ET-1 treatment caused Ser/Thr
      phosphorylation of IRS-1 and IRS-1 protein degradation. Overexpression of KD
      GRK2, but not WT-GRK2, inhibited ET-1-induced serine 612 phosphorylation of IRS-1
      and restored activation of this pathway. Taken together, these results suggest
      that GRK2 mediates ET-1-induced insulin resistance by 1) inhibition of Galphaq/11
      activation, and this effect is independent of GRK2 kinase activity, and 2) GRK2
      kinase activity-mediated IRS-1 serine phosphorylation and degradation.

PMID- 15994204
TI  - In situ HVEM study on copper oxidation using an improved environmental cell.
AB  - A window-type environmental cell that can be used over the temperature range from
      room temperature to approximately 1000 K was improved by incorporating a new
      window material that increases resolution and contrast in high voltage electron
      microscopy. With this improvement, the resolution was a few nanometers and the
      maximum pressure in the cell was approximately 1.3 x 10(4) Pa. Using this new
      window-type environmental cell, oxidation of copper and reduction of copper
      oxides, which occur through gas (oxygen or hydrogen)-solid (copper metal)
      reactions, have been successfully observed in situ, i.e. the formation process of
      oxides (Cu --> Cu2O --> CuO) and their subsequent reduction (CuO --> Cu) in the
      cell. The growth process of CuO whiskers on a thick (50 microm) Cu film was also
      observed in situ. It was found that whisker growth occurs at the tips of
      whiskers.

PMID- 15994205
TI  - Role of mitochondria in the switch mechanism of the cell death mode from
      apoptosis to necrosis--studies on rho0 cells.
AB  - Detailed mechanisms of the switch of the cell death mode from apoptosis to
      necrosis remain to be solved, although the intracellular level of ATP and that of
      free radicals have been postulated to be the major factors involved in the
      mechanisms. In the present study menadione (MEN)-induced cell injury processes
      were studied using rho0 cells derived from human osteosarcoma 143B cells and
      parental rho+ cells co-treated with inhibitors of electron transfer chain of
      mitochondria or oligomycin, an inhibitor of ATP synthesis. Treatment of rho+
      cells with 100 microM MEN induced apoptosis, which reached the maximum at 6 h,
      and was followed by an abrupt decrease thereafter, while necrotic cells (NC)
      increased continuously when they were judged by Annexin V and PI double staining.
      On the other hand, MEN induced apoptotic and necrotic changes much faster in rho0
      cells compared to rho+ cells. The frequency to find apoptotic cells (AP) in the
      former cells was distinctly smaller than that to find NC judged by Annexin V and
      PI double staining. Electron microscopically, a major population of rho0 cells
      treated with MEN for 6 h consisted of intermediate cells, and a small number of
      AP co-existed. At 9 h of the treatment intermediate cells were exclusively seen,
      and AP were hardly detected. When parental rho+ cells were treated with MEN in
      the presence of oligomycin or oligomycin plus antimycin A both apoptotic and
      necrotic changes of the cells were distinctly accelerated. The intracellular
      level of superoxide in rho0 cells continuously increased after the MEN treatment,
      whereas that of ATP remained distinctly low before and after the MEN treatment
      compared to that in rho+ cells. These data suggest that the intracellular level
      of superoxide may be a key factor controlling the switch from apoptosis to
      necrosis.

PMID- 15994206
TI  - The potential of the scanning low energy electron microscopy for the examination
      of aluminum based alloys and composites.
AB  - When studying the physical properties and technological parameters of aluminum
      based alloys and composites, some partial tasks, connected with the
      microstructure of the material bulk, pose a problem for established microscopic
      techniques. The topography and distribution of sub-micrometer sized precipitates
      and of segregations on the particle/matrix interface, for example, are difficult
      to observe by conventional methods of transmission and scanning electron
      microscopy. The introduction of a high-resolution low-energy mode into the
      scanning electron microscope, relying on the deceleration of an already formed
      and focused primary beam just in front of the specimen, enables one to browse
      over the full electron energy range with great ease. This method offers added
      value consisting of the diminished interaction volume of electrons, the favorable
      combination of secondary and backscattered electron signals emitted at increased
      yields and collected at extremely high efficiency and the availability of
      unconventional contrasts excited by slow electrons. Demonstration experiments
      have been performed on structures based on the Al-Mg-Si alloy, and oriented
      towards examination of the Mg-Si precipitates in the alloy and sub-micrometer
      spinel crystals growing on the matrix-ceramic interface in a composite filled
      with alumina particles.

PMID- 15994207
TI  - Development of a real-time stereo transmission electron microscope.
AB  - A new transmission electron microscope that allows for stereoscopic observations
      in real time at a video rate has been developed. In order to make stereo pairs at
      a high speed, illumination of a specimen from two directions instead of specimen
      tilting is adopted. Two electrostatic deflectors make it possible to alternate
      the illumination direction within a blank period of 1.2 ms between two adjacent
      video fields. Three dimensional displays give observers a stereo impression
      without the need for special glasses. By considering the circle of least
      confusion due to spherical aberration, a lateral resolution <1 nm and a
      longitudinal resolution of 6.3 nm are possible with a proper defocused condition.
      This improvement of the resolution is confirmed for the image of Au fine
      particles. The motion of objects in the lateral direction can be detected up to a
      speed of 8.3 nm s(-1). Using this microscope fine particles of ZnO were observed.

PMID- 15994208
TI  - Will we find biomarkers of aging?

PMID- 15994209
TI  - How can we use moderate stresses to fortify humans and slow aging?

PMID- 15994210
TI  - How can we craft a better theory to explain the evolution of aging?

PMID- 15994211
TI  - Engine trouble.

PMID- 15994212
TI  - Falling apart.

PMID- 15994213
TI  - Metabolomics: opening another window into aging.
AB  - Metabolomics is based on the simultaneous analysis of multiple low-molecular
      weight metabolites from a given sample. As such, metabolomics seeks the most up
      to-date information about the state of interaction between an organism and its
      environment. The ability to use metabolomics approaches for classification and
      mechanistic studies may influence and augment our ability to study and address
      the aging process scientifically and clinically.

PMID- 15994214
TI  - Reactive oxygen species and aging: evolving questions.
AB  - Over the past 50 years, reactive oxygen species (ROS) have been investigated as
      putative mediators of the process of aging. As specific genes and pathways that
      are involved with ROS homeostasis have been linked to aging in lower organisms,
      such as Caenorhabditis elegans and Drosophila, the questions of how ROS regulate
      aging in higher organisms, and whether they do so to the same extent as in lower
      organisms, have emerged.

PMID- 15994215
TI  - 5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a
      large epidemiological study.
AB  - BACKGROUND AND AIMS: The objective of this study was to evaluate the risk of
      colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for
      inflammatory bowel disease (IBD). METHODS: The General Practice Research Database
      (GPRD) which contains the primary care records of five million people in the UK
      was used to identify users of mesalazine, balsalazide, olsalazine, or
      sulfasalazine with a history of IBD. In a nested case control analysis, each
      incident CRC case with any use of a 5-ASA in the six months before the CRC
      diagnosis was matched by age, sex, and calendar time to six control patients who
      were also currently using a 5-ASA. Patients were then classified according to
      regularity of use. The analysis was controlled for body mass index, IBD duration,
      history of colorectal polyps, use of non-steroidal anti-inflammatory drugs,
      paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior
      gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to
      the general practitioner for IBD symptoms in the 6-24 months before diagnosis.
      RESULTS: The study population included 18 969 patients, of whom 100 had developed
      CRC during 5-ASA exposure. Most of these cases had a history of ulcerative
      colitis (76 patients). In the case control analysis, regular users, defined as
      having six or more 5-ASA prescriptions in the previous 12 months, were found to
      have a decreased risk of CRC compared with irregular users (crude odds ratio (OR)
      0.7 (0.44-1.03); adjusted OR 0.60 (0.38-0.96)). Regular users of sulfasalazine
      with 6-12 prescriptions before had an adjusted OR of 0.95 (0.22-4.11); with 13-30
      prior prescriptions this was 0.41 (0.14-1.20) and with >30 prior prescriptions
      this was 0.77 (0.37-1.60). For mesalazine users, these values were 1.13 (0.49
      2.59), 0.30 (0.11-0.83), and 0.31 (0.11-0.84), respectively. CONCLUSION: These
      results show that regular 5-ASA use is associated with some reduction in the risk
      of CRC developing in ulcerative colitis.

PMID- 15994216
TI  - Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for
      histologically mild chronic hepatitis C.
AB  - BACKGROUND: For patients with mild chronic hepatitis C the cost effectiveness of
      antiviral therapy is unknown. AIMS: To assess whether antiviral therapy (either
      interferon alpha or peginterferon alpha combined with ribavirin) is cost
      effective at a mild stage compared with waiting and only treating those cases who
      progress to moderate disease. PATIENTS: Cases with mild chronic hepatitis C.
      METHODS: A cost effectiveness model which estimates long term costs and outcomes
      for patients with mild chronic hepatitis C. The model uses effectiveness and cost
      data from the UK mild hepatitis C randomised controlled trial, combined with
      estimates of disease progression and cost from observational studies. RESULTS:
      Antiviral treatment at a mild rather than a moderate stage improved outcomes
      measured by quality adjusted life years (QALYS) gained. The mean cost per QALY
      gained from antiviral treatment with interferon alpha-2b and ribavirin, compared
      with no treatment at a mild stage, was 4535 pounds sterling (7108 dollars) for
      patients with genotype non-1 and 25,188 pounds sterling (39,480 dollars) for
      patients with genotype 1. Providing peginterferon alpha-2b and ribavirin at a
      mild rather than a moderate stage was also associated with a gain in QALYS; the
      costs per QALY gained were 7821 pounds sterling (12,259 dollars) for patients
      with genotype non-1 and 28,409 pounds sterling (44,528 dollars) for patients with
      genotype 1. CONCLUSIONS: For patients with chronic hepatitis C, it is generally
      more cost effective to provide antiviral treatment at a mild rather than a
      moderate disease stage. For older patients (aged 65 years or over) with genotype
      1, antiviral treatment at a mild stage is not cost effective.

PMID- 15994217
TI  - Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects
      of peripheral ghrelin in rats.
AB  - BACKGROUND AND AIMS: Ghrelin, the natural ligand of the growth hormone
      secretagogue receptor 1a, is the most powerful peripherally active orexigenic
      agent known. In rodents, ghrelin administration stimulates growth hormone
      release, food intake, and adiposity. Because of these effects, blocking of
      ghrelin has been widely discussed as a potential treatment for obesity.
      Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown
      to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal
      activation and food intake in non-fasted rats. METHODS: Animals received various
      doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin
      or vehicle was administered intraperitoneally 12 hours later and food intake was
      measured over four hours. Neuronal activation was assessed as c-Fos-like
      immunoreactivity in the arcuate nucleus. RESULTS: Treatment with NOX-B11 30 nmol
      suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and
      blocked the ghrelin induced increase in food intake within the first half hour
      after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg
      body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX
      B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10
      nmol showed an intermediate effect on ghrelin induced food intake. CONCLUSIONS:
      Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in
      the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an
      innovative new approach to inhibit the biological action of circulating ghrelin.
      This may be of particular relevance to conditions associated with elevated plasma
      ghrelin, such as the Prader-Willi syndrome.

PMID- 15994219
TI  - Sleep issues in Parkinson's disease.
AB  - Sleep disturbances in patients with Parkinson's disease (PD) are common, are
      often severe, and are typically underrecognized and ineffectively treated. After
      the recognition that some patients with PD could fall asleep unexpectedly when
      driving, with resulting dangerous consequences, it became evident not only that
      PD medications might be partly responsible but that there were many additional
      factors contributing to sleep disturbance in these patients. This review
      discusses the myriad sleep disorders seen in patients with PD, presents their
      diagnostic features, and gives recommendations on their management. Effective
      management of sleep disturbances and excessive daytime sleepiness can greatly
      improve the quality of life for patients with PD.

PMID- 15994220
TI  - Current treatments of epilepsy.
AB  - Medical therapy is the mainstay for epilepsy, with most patients well controlled
      on a single antiepileptic drug (AED). In this non-refractory group, many patients
      have medication side effects and occasional seizures. Approximately 30% of
      patients with partial epilepsy and 25% of patients with generalized epilepsy are
      not well controlled on medications. These patients are often receiving multiple
      AEDs, with disabling seizures and side effects. Although second-generation AEDs
      are safer and better tolerated than the older AEDs, there are scant data to
      support significant advantages in efficacy. In VA studies with older AEDS,
      therapy with two AEDs improved seizure control in 40% of patients but seizure
      freedom was achieved in only 9%. A meta-analysis of the second-generation AEDs
      used as adjunctive therapies shows that 12% to 29% of patients had a 50% or
      greater reduction in seizure frequency. Surgery and the vagus nerve stimulator
      provide important therapeutic options in patients whose seizures are not
      controlled by AEDs. Special considerations about epilepsy care must be made in
      pediatric populations, those with developmental delays, women, and the elderly.

PMID- 15994221
TI  - New paradigms in the treatment of restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a common neurologic disorder occurring in 3% to
      15% of the general population, which contributes to poor quality of life. Many
      patients go undiagnosed for years after onset of symptoms, which delays or
      prevents effective treatment. Extensive research over the past decade has led to
      a better understanding of RLS and effective treatment options. This review
      encompasses the most recently published pathophysiology, epidemiology, criteria
      for diagnosis, and clinical drug efficacy trials to provide clinicians with the
      information to effectively manage RLS. A comprehensive review of the medical
      literature was conducted and original research articles pertaining to RLS were
      evaluated. The pathophysiology of primary RLS is associated with dopaminergic
      dysfunction and abnormal brain iron metabolism. Secondary RLS is most often a
      consequence of iron deficiency. The prevalence of primary RLS is twofold greater
      in women and increases with age in men and women, although onset of symptoms may
      occur in up to 45% of patients before age 20 years. Patients may present with a
      variety of complaints including sleep disruption. Several studies have
      demonstrated the efficacy of low-dose levodopa and dopamine agonists. Ropinirole
      is the most widely studied. Other drugs that may help control symptoms include
      gabapentin, opioids, and clonazepam. Clinicians must be aware of the high
      prevalence of RLS, the potential for onset before age 20, and the various
      clinical presentations. Dopamine agonists are first-line therapy and provide
      symptom relief in 70% to 100% of patients.

PMID- 15994222
TI  - Diagnosis and treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most
      common cause of dementia. It is one of the principal causes of disability and
      decreased quality of life among older adults. Progress in our clinical knowledge
      of AD has led to more reliable diagnostic criteria and accuracy, and research
      efforts are expanding to uncover the earliest manifestations and even the
      presymptomatic phases of the disease. The diagnosis of AD is primarily one of
      inclusion and usually can be made using standardized clinical criteria. There is
      currently no cure for AD. Current treatment focuses on establishing an early
      accurate clinical diagnosis, early institution of cholinesterase inhibitors
      and/or N-methyl-D-aspartate (NMDA) receptor-targeted therapy. Treating medical
      comorbidities and dementia-related complications, ensuring that appropriate
      services are provided, addressing the long-term well-being of caregivers, and
      treating behavioral and psychological symptoms with appropriate nonpharmacologic
      and pharmacologic interventions also are important. The initiating and
      propagating pathologic processes and the anatomic location of the earliest
      changes will become new targets of research and therapeutic development. A
      possible precursor of AD, mild cognitive impairment (MCI), is under investigation
      as a possible therapeutic starting point for disease-modifying interventions.
      This article provides a research update of current understanding in the diagnosis
      and treatment of AD and in emerging areas of interest such as MCI, detection of
      AD in the predementia phase, and neuroimaging in AD.

PMID- 15994223
TI  - Endothelial expression of constitutively active Notch4 elicits reversible
      arteriovenous malformations in adult mice.
AB  - Direct communication between arteries and veins without intervening capillary
      beds is the primary pathology of arteriovenous malformations (AVMs). Although
      Notch signaling is implicated in embryonic arteriovenous (AV) differentiation,
      its function in the adult mammalian vasculature has not been established due to
      the embryonic lethality that often occurs in both gain- and loss-of-function
      mutants. We expressed a constitutively active Notch4, int3, in the adult mouse
      endothelium by using the tetracycline-repressible system to suppress int3 during
      embryogenesis. int3 caused profound blood vessel enlargement and AV shunting,
      which are hallmarks of AVM, and led to lethality within weeks of its expression.
      Vessel enlargement, a manifestation of AVM, occurred in an apparently tissue
      specific fashion; the liver, uterus, and skin were affected. int3-mediated
      vascular defects were accompanied by arterialization, including ectopic venous
      expression of ephrinB2, increased smooth muscle cells, and up-regulation of
      endogenous Notch signaling. Remarkably, the defective vessels and illness were
      reversed upon repression of int3 expression. Finally, endothelial expression of a
      constitutively active Notch1 induced similar hepatic vascular lesions. Our
      results provide gain-of-function evidence that Notch signaling in the adult
      endothelium is sufficient to render arterial characteristics and lead to AVMs.

PMID- 15994224
TI  - Fisher's theorems for multivariable, time- and space-dependent systems, with
      applications in population genetics and chemical kinetics.
AB  - We study different physical, chemical, or biological processes involving
      replication, transformation, and disappearance processes, as well as transport
      processes, and assume that the time and space dependence of the species densities
      are known. We derive two types of Fisher equations. The first type relates the
      average value of the time derivative of the relative time-specific rates of
      growth of the different species to the variance of the relative, time-specific
      rates of growth. A second type relates the average value of the gradient or the
      divergence of the relative, space-specific rates of growth to the space
      correlation matrix of the relative, space-specific rates of growth. These Fisher
      equations are exact results, which are independent of the detailed kinetics of
      the process: they are valid whether the evolution equations are linear or
      nonlinear, local or nonlocal in space and/or time and can be applied for the
      study of a large class of physical, chemical, and biological systems described in
      terms of time- and/or space-dependent density fields. We examine the implications
      of our generalized Fisher relations in population genetics, biochemistry, and
      chemical kinetics (reaction-diffusion systems). We show that there is a
      connection between the enhanced (hydrodynamic) transport of mutations induced by
      population growth and space-specific rate vectors: the velocity of enhanced
      transport is proportional to the product of the diffusion coefficient of the
      species and the space rate vector; this relation is similar to a fluctuation
      dissipation relation in statistical mechanics.

PMID- 15994225
TI  - The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene
      transcription and tumorigenesis of prostate cancer cells.
AB  - Down-regulation of the androgen receptor (AR) is being evaluated as an effective
      therapy for the advanced stages of prostate cancer. We report that Ebp1, a
      protein identified by its interactions with the ErbB3 receptor, down-regulates
      expression of AR and AR-regulated genes in the LNCaP prostate cancer cell line.
      Using microarray analysis, we identified six endogenous AR target genes,
      including the AR itself, that are down-regulated by ebp1 overexpression.
      Chromatin immunoprecipitation assays revealed that Ebp1 was recruited to the
      prostate-specific antigen gene promoter in response to the androgen antagonist
      bicalutamide, suggesting that Ebp1 directly affected the expression of AR
      regulated genes in response to androgen antagonists. Ebp1 expression was reduced
      in cells that had become androgen-independent. Androgens failed to stimulate
      either the growth of ebp1 transfectants or transcription of AR-regulated reporter
      genes in these cells. The agonist activity of the antiandrogen cyproterone
      acetate was abolished in ebp1 transfectants. In severe combined immunodeficient
      mice, Ebp1 overexpression resulted in a reduced incidence of LNCaP tumors and
      slower tumor growth. These findings suggest that Ebp1 is a previously
      unrecognized therapeutic target for treatment of hormone refractory prostate
      cancer.

PMID- 15994226
TI  - Iron-rich silicates in the Earth's D'' layer.
AB  - High-pressure experiments and theoretical calculations demonstrate that an iron
      rich ferromagnesian silicate phase can be synthesized at the pressure-temperature
      conditions near the core-mantle boundary. The iron-rich phase is up to 20% denser
      than any known silicate at the core-mantle boundary. The high mean atomic number
      of the silicate greatly reduces the seismic velocity and provides an explanation
      to the low-velocity and ultra-low-velocity zones. Formation of this previously
      undescribed phase from reaction between the silicate mantle and the iron core may
      be responsible for the unusual geophysical and geochemical signatures observed at
      the base of the lower mantle.

PMID- 15994227
TI  - Soluble epoxide hydrolase is a therapeutic target for acute inflammation.
AB  - As of 2004, >73 million people were prescribed antiinflammatory medication.
      Despite the extensive number of current products, many people still suffer from
      their diseases or the pharmacological properties (side effects) of the
      medications. Therefore, developing therapeutic strategies to treat inflammation
      remains an important endeavor. Here, we demonstrate that the soluble epoxide
      hydrolase (sEH) is a key pharmacologic target for treating acute systemic
      inflammation. Lipopolysaccharide-induced mortality, systemic hypotension, and
      histologically evaluated tissue injury were substantially diminished by
      administration of urea-based, small-molecule inhibitors of sEH to C57BL/6 mice.
      Moreover, sEH inhibitors decreased plasma levels of proinflammatory cytokines and
      nitric oxide metabolites while promoting the formation of lipoxins, thus
      supporting inflammatory resolution. These data suggest that sEH inhibitors have
      therapeutic efficacy in the treatment and management of acute inflammatory
      diseases.

PMID- 15994228
TI  - Hypnotic suggestion reduces conflict in the human brain.
AB  - Many studies have suggested that conflict monitoring involves the anterior
      cingulate cortex (ACC). We previously showed that a specific hypnotic suggestion
      reduces involuntary conflict and alters information processing in highly
      hypnotizable individuals. Hypothesizing that such conflict reduction would be
      associated with decreased ACC activation, we combined neuroimaging methods to
      provide high temporal and spatial resolution and studied highly and less
      hypnotizable participants both with and without a suggestion to interpret visual
      words as nonsense strings. Functional MRI data revealed that under posthypnotic
      suggestion, both ACC and visual areas presented reduced activity in highly
      hypnotizable persons compared with either no-suggestion or less-hypnotizable
      controls. Scalp electrode recordings in highly hypnotizable subjects also showed
      reductions in posterior activation under suggestion, indicating visual system
      alterations. Our findings illuminate how suggestion affects cognitive control by
      modulating activity in specific brain areas, including early visual modules, and
      provide a more scientific account relating the neural effects of suggestion to
      placebo.

PMID- 15994229
TI  - Single-molecule studies of repressor-DNA interactions show long-range
      interactions.
AB  - We have performed single-molecule studies of GFP-LacI repressor proteins bound to
      bacteriophage lambda DNA containing a 256 tandem lac operator insertion confined
      in nanochannels. An integrated photon molecular counting method was developed to
      determine the number of proteins bound to DNA. By using this method, we
      determined the saturated mean occupancy of the 256 tandem lac operators to be 13,
      which constitutes only 2.5% of the available sites. This low occupancy level
      suggests that the repressors influence each other even when they are widely
      separated, at distances on the order of 200 nm, or several DNA persistence
      lengths.

PMID- 15994230
TI  - Telomerase can act as a template- and RNA-independent terminal transferase.
AB  - Telomerase is a special reverse transcriptase that extends one strand of the
      telomere repeat by using a template embedded in an RNA subunit. Like other
      polymerases, telomerase is believed to use a pair of divalent metal ions
      (coordinated by a triad of aspartic acid residues) for catalyzing nucleotide
      addition. Here we show that, in the presence of manganese, both yeast and human
      telomerase can switch to a template- and RNA-independent mode of DNA synthesis,
      acting in effect as a terminal transferase. Even as a terminal transferase, yeast
      telomerase retains a species-dependent preference for GT-rich, telomere-like DNA
      on the 5' end of the substrate. The terminal transferase activity of telomerase
      may account for some of the hitherto unexplained effects of telomerase
      overexpression on cell physiology.

PMID- 15994231
TI  - Interferon prevents formation of replication-competent hepatitis B virus RNA
      containing nucleocapsids.
AB  - We have previously shown that IFN-beta inhibits hepatitis B virus (HBV)
      replication by noncytolytic mechanisms that either destabilize pregenomic (pg)RNA
      containing capsids or prevent their assembly. Using immortalized murine
      hepatocyte cell lines stably transfected with a doxycycline (dox)-inducible HBV
      replication system, we now show that replication-competent pgRNA-containing
      capsids are not produced when the cells are pretreated with IFN-beta before HBV
      expression is induced with dox. Furthermore, the turnover rate of preformed HBV
      RNA-containing capsids is not changed in the presence of IFN-beta or IFN-gamma
      under conditions in which further pgRNA synthesis is inhibited by dox removal. In
      summary, these results demonstrate that types 1 and 2 IFN activate hepatocellular
      mechanism(s) that prevent the formation of replication-competent HBV capsids and,
      thereby, inhibit HBV replication.

PMID- 15994232
TI  - Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha
      actinin are components of the nephrin multiprotein complex.
AB  - Nephrin is a cell surface receptor of the Ig superfamily that localizes to slit
      diaphragms, the specialized junctions between the interdigitating foot processes
      of the glomerular epithelium (podocytes) in the kidney. Mutations in the NPHS1
      gene encoding nephrin lead to proteinuria and congenital nephrotic syndrome,
      indicating that nephrin is essential for normal glomerular development and
      function. To identify nephrin-binding proteins, we performed mass spectrometry on
      proteins obtained from pull-down assays with GST-nephrin cytoplasmic domain.
      Nephrin specifically pulled down six proteins from glomerular lysates, MAGI-2/S
      SCAM (membrane-associated guanylate kinase inverted 2/synaptic scaffolding
      molecule), IQGAP1 (IQ motif-containingGTPase
      activatingprotein1),CASK(calcium/calmodulin-dependent serine protein kinase),
      alpha-actinin, alphaII spectrin, and betaII spectrin. All of these scaffolding
      proteins are often associated with cell junctions. By immunofluorescence these
      proteins are expressed in glomerular epithelial cells, where they colocalize with
      nephrin in the foot processes. During glomerular development, IQGAP1 is expressed
      in the junctional complexes between the earliest identifiable podocytes, MAGI-2/S
      SCAM is first detected in junctional complexes in podocytes after their migration
      to the base of the cells. Thus, the nephrin-slit diaphragm protein complex
      contains a group of scaffolding proteins that function to connect junctional
      membrane proteins to the actin cytoskeleton and signaling cascades. Despite their
      special morphology and function, there is considerable compositional similarity
      between the podocyte slit diaphragm and typical junctional complexes of other
      epithelial cells.

PMID- 15994233
TI  - Inducible costimulator is required for type 2 antibody isotype switching but not
      T helper cell type 2 responses in chronic nematode infection.
AB  - Inducible costimulator (ICOS) has been suggested to perform an important role in
      T helper cell type 2 (Th2) responses, germinal center formation, and isotype
      switching. The role of ICOS in chronic Th2 responses was studied in a nematode
      model with the filarial parasite, Brugia malayi. Contrary to expectations, we did
      not observe a significant defect in IL-4-producing Th2 cells in ICOS-/- mice or
      in eosinophil recruitment. We also found that ICOS was not required for the
      differentiation of alternatively activated macrophages (AAMPhi) that express Ym1
      and Fizz1. Although the production of IgE was slightly reduced in ICOS-/- mice,
      this was not as significant as in CD28-/- mice. In contrast to live infection,
      the primary response of ICOS-/- mice immunized with soluble B. malayi antigen and
      complete Freund's adjuvant resulted in significantly fewer IL-4-producing cells
      in the lymph nodes. As previously reported, we observed a defect in antibody
      isotype switching toward the IgG1 isotype in ICOS-/- mice during live infection.
      Interestingly, there was a significant enhancement of parasite-specific IgG3
      isotype antibodies. CD28-/- and MHC class II-/- mice also had enhanced parasite
      specific IgG3 isotype antibodies. Our results suggest that ICOS is not required
      to maintain a chronic cellular Th2 response. The primary role of ICOS in a
      chronic helminth infection could be to drive antibodies toward type 2 isotypes. T
      independent antibody response to the parasite could be enhanced in the absence of
      costimulation and T cell help.

PMID- 15994235
TI  - On soliton propagation in biomembranes and nerves.
AB  - The lipids of biological membranes and intact biomembranes display chain melting
      transitions close to temperatures of physiological interest. During this
      transition the heat capacity, volume and area compressibilities, and relaxation
      times all reach maxima. Compressibilities are thus nonlinear functions of
      temperature and pressure in the vicinity of the melting transition, and we show
      that this feature leads to the possibility of soliton propagation in such
      membranes. In particular, if the membrane state is above the melting transition
      solitons will involve changes in lipid state. We discuss solitons in the context
      of several striking properties of nerve membranes under the influence of the
      action potential, including mechanical dislocations and temperature changes.

PMID- 15994234
TI  - HOS10 encodes an R2R3-type MYB transcription factor essential for cold
      acclimation in plants.
AB  - We report the identification and characterization of an Arabidopsis mutant, hos10
      1 (for high expression of osmotically responsive genes), in which the expression
      of RD29A and other stress-responsive genes is activated to higher levels or more
      rapidly activated than in wild-type by low temperature, exogenous abscisic acid
      (ABA), or salt stress (NaCl). The hos10-1 plants are extremely sensitive to
      freezing temperatures, completely unable to acclimate to the cold, and are
      hypersensitive to NaCl. Induction of NCED3 (the gene that encodes the rate
      limiting enzyme in ABA biosynthesis) by polyethylene glycol-mediated dehydration
      and ABA accumulation are reduced by this mutation. Detached shoots from the
      mutant plants display an increased transpiration rate compared with wild-type
      plants. The hos10-1 plants exhibit several developmental alterations, such as
      reduced size, early flowering, and reduced fertility. The HOS10 gene encodes a
      putative R2R3-type MYB transcription factor that is localized to the nucleus.
      Together, these results indicate that HOS10 is an important coordinating factor
      for responses to abiotic stress and for growth and development.

PMID- 15994236
TI  - The structural basis of androgen receptor activation: intramolecular and
      intermolecular amino-carboxy interactions.
AB  - Nuclear receptors (NRs) are ligand-regulated transcription factors important in
      human physiology and disease. In certain NRs, including the androgen receptor
      (AR), ligand binding to the carboxy-terminal domain (LBD) regulates
      transcriptional activation functions in the LBD and amino-terminal domain (NTD).
      The basis for NTD-LBD communication is unknown but may involve NTD-LBD
      interactions either within a single receptor or between different members of an
      AR dimer. Here, measurement of FRET between fluorophores attached to the NTD and
      LBD of the AR established that agonist binding initiated an intramolecular NTD
      LBD interaction in the nucleus and cytoplasm. This intramolecular folding was
      followed by AR self-association, which occurred preferentially in the nucleus.
      Rapid, ligand-induced intramolecular folding and delayed association also were
      observed for estrogen receptor-alpha but not for peroxisome proliferator
      activated receptor-gamma2. An antagonist ligand, hydroxyflutamide, blocked the
      NTD-LBD association within AR. NTD-LBD association also closely correlated with
      the transcriptional activation by heterologous ligands of AR mutants isolated
      from hormone-refractory prostate tumors. Intramolecular folding, but not AR-AR
      affinity, was disrupted by mutation of an alpha-helical ((23)FQNLF(27)) motif in
      the AR NTD previously described to interact with the AR LBD in vitro. This work
      establishes an intramolecular NTD-LBD conformational change as an initial
      component of ligand-regulated NR function.

PMID- 15994237
TI  - Eph kinases and ephrins support thrombus growth and stability by regulating
      integrin outside-in signaling in platelets.
AB  - The ability of activated platelets to adhere to each other at sites of vascular
      injury depends on the integrin alpha(IIb)beta(3). However, as aggregation
      continues, other signaling and adhesion molecules can contribute as well. We have
      previously shown that human platelets express on their surface the Eph receptor
      kinases EphA4 and EphB1 and the Eph kinase ligand ephrinB1. We now show that
      EphA4 is physically associated with alpha(IIb)beta(3) in resting platelets,
      increases its surface expression when platelets are activated, and colocalizes
      with alpha(IIb)beta(3) at sites of contact between platelets. We also show that
      Eph/ephrin interactions can support the stable accumulation of platelets on
      collagen under flow and contribute to postengagement "outside-in" signaling
      through alpha(IIb)beta(3) by stabilizing platelet aggregates and facilitating
      tyrosine phosphorylation of the beta(3) cytoplasmic domain. beta(3)
      phosphorylation allows myosin to bind to alpha(IIb)beta(3) and clot retraction to
      occur. The data support a model in which the onset of aggregation permits
      Eph/ephrin interactions to occur, after which signaling downstream from ephrinB1
      and its receptors favors continued growth and stability of the thrombus by
      several mechanisms, including positive effects on outside-in signaling through
      alpha(IIb)beta(3).

PMID- 15994238
TI  - Comparison between the effect of static contraction and tendon stretch on the
      discharge of group III and IV muscle afferents.
AB  - The exercise pressor reflex is evoked by both mechanical and metabolic stimuli.
      Tendon stretch does not increase muscle metabolism and therefore is used to
      investigate the mechanical component of the exercise pressor reflex. An important
      assumption underlying the use of tendon stretch to study the mechanical component
      of the exercise pressor reflex is that stretch stimulates the same group III
      mechanosensitive muscle afferents as does static contraction. We have tested the
      veracity of this assumption in decerebrated cats by comparing the responses of
      group III and IV muscle afferents to tendon stretch with those to static
      contraction. The tension-time indexes as well as the peak tension development for
      both maneuvers did not significantly differ. We found that static contraction of
      the triceps surae muscles stimulated 18 of 30 group III afferents and 8 of 11
      group IV afferents. Similarly, tendon stretch stimulated 14 of 30 group III
      afferents and 3 of 11 group IV afferents. However, of the 18 group III afferents
      that responded to static contraction and the 14 group III afferents that
      responded to tendon stretch, only 7 responded to both stimuli. On average, the
      conduction velocities of the 18 group III afferents that responded to static
      contraction (11.6 +/- 1.6 m/s) were significantly slower (P = 0.03) than those of
      the 14 group III afferents that responded to tendon stretch (16.7 +/- 1.5 m/s).
      We have concluded that tendon stretch stimulated a different population of group
      III mechanosensitive muscle afferents than did static contraction. Although there
      is some overlap between the two populations of group III mechanosensitive
      afferents, it is not large, comprising less than half of the group III afferents
      responding to static contraction.

PMID- 15994239
TI  - No effect of short-term testosterone manipulation on exercise substrate
      metabolism in men.
AB  - Compared with women, men use proportionately more carbohydrate and less fat
      during exercise at the same relative intensity. Estrogen and progesterone have
      potent effects on substrate use during exercise in women, but the role of
      testosterone (T) in mediating substrate use is unknown. The purpose of this
      investigation was to assess how large variations in the concentration of blood T
      would impact substrate use during exercise in men. Nine healthy, active men were
      studied in three distinct hormonal conditions: physiological T (no intervention),
      low T (pharmacological suppression of endogenous T with a gonadotrophin-releasing
      hormone antagonist), and high T (supplementation with transdermal T). Total
      carbohydrate oxidation, blood glucose rate of disappearance, and estimated muscle
      glycogen use were assessed by using stable isotope dilution and indirect
      calorimetry at rest and while bicycling at approximately 60% of peak O2
      consumption for 90 min. Relative to the physiological condition (T = 5.5 +/- 0.5
      ng/ml), total plasma T was considerably suppressed in low T (0.8 +/- 0.1) and
      elevated in high T (10.9 +/- 1.1). Despite the large changes in plasma T,
      carbohydrate oxidation, glucose rate of disappearance, and estimated muscle
      glycogen use were very similar across the three conditions. There were also no
      differences in plasma concentrations of glucose, insulin, lactate, or free fatty
      acids. Plasma estradiol (E) concentrations were elevated in high T, but
      correlations between substrate use and plasma concentrations of T, E, or the T-to
      E ratio were very weak (r2 < 0.20). In conclusion, unlike the effect of acute
      elevation in E to constrain carbohydrate use in women, acute changes in
      circulating T concentrations do not appear to alter substrate use during exercise
      in men.

PMID- 15994240
TI  - Stimulatory effect of CO2 on vagal bronchopulmonary C-fiber afferents during
      airway inflammation.
AB  - This study investigated 1) whether pulmonary C fibers are activated by a
      transient increase in the CO2 concentration of alveolar gas; and 2) if the CO2
      sensitivity of these afferents is altered during airway inflammation. Single-unit
      pulmonary C-fiber activity was recorded in anesthetized, open-chest rats.
      Transient alveolar hypercapnia (HPC) was induced by administering a CO2-enriched
      gas mixture (25-30% CO2, 21% O2, balance N2) for five to eight breaths, which
      increased alveolar CO2 concentration progressively to near or above 13% for 3-5 s
      and lowered the arterial pH transiently to 7.10 +/- 0.05. Our results showed the
      following. 1) HPC evoked only a mild stimulation in a small fraction (4/47) of
      pulmonary C fibers, and there was no significant change in fiber activity (change
      in fiber activity = 0.22 +/- 0.16 imp/s; P > 0.1, n = 47). 2) In sharp contrast,
      after airway exposure to poly-L-lysine, a cationic protein known to induce
      mucosal injury, the same challenge of transient HPC activated 87.5% of the
      pulmonary C fibers tested and evoked a distinct stimulatory effect on these
      afferents (change in fiber activity = 6.59 +/- 1.78 imp/s; P < 0. 01, n = 8). 3)
      Similar potentiation of the C-fiber response to HPC was also observed after acute
      exposure to ozone (n = 6) and during a constant infusion of inflammatory
      mediators such as adenosine (n = 15) or prostaglandin E2 (n = 12). 4) The
      enhanced C-fiber sensitivity to CO2 after poly-L-lysine was completely abrogated
      by infusion of NaHCO3 (1.82 mmol.kg(-1).min(-1)) that prevented the reduction in
      pH during HPC (n = 6). In conclusion, only a small percentage (<10%) of the
      bronchopulmonary C fibers exhibit CO2 sensitivity under control conditions, but
      alveolar HPC exerts a consistent and pronounced stimulatory effect on the C-fiber
      endings during airway inflammation. This effect of CO2 is probably mediated
      through the action of hydrogen ions.

PMID- 15994241
TI  - Arg16/Gly beta2-adrenergic receptor polymorphism alters the cardiac output
      response to isometric exercise.
AB  - Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2
      adrenergic-receptor polymorphism have 1) greater forearm beta2-receptor mediated
      vasodilation and 2) a higher heart rate (HR) response to isometric handgrip than
      arginine (Arg) homozygotes. To test the hypothesis that the higher HR response in
      Gly16 subjects serves to maintain the pressor response [increased cardiac output
      (CO)] in the setting of augmented peripheral vasodilation to endogenous
      catecholamines, we measured continuous HR (ECG), arterial pressure (Finapres),
      and CO (transthoracic echocardiography) during isometric, 40% submaximal handgrip
      to fatigue in healthy subjects homozygous for Gly (n = 30; mean age +/- SE: 30 +/
      1.2, 13 women) and Arg (n = 17, age 30 +/- 1.6, 11 women). Resting data were
      similar between groups. Handgrip produced similar increases in arterial pressure
      and venous norepinephrine and epinephrine concentrations; however, HR increased
      more in the Gly group (60.1 +/- 4.3% increase from baseline vs. 45.5 +/- 3.9%, P
      = 0.03), and this caused CO to be higher (Gly: 7.6 +/- 0.3 l/m vs. Arg: 6.5 +/-
      0.3 l/m, P = 0.03), whereas the decrease in systemic vascular resistance in the
      Gly group did not reach significance (P = 0.09). We conclude that Gly16
      homozygotes generate a higher CO to maintain the pressor response to handgrip.
      The influence of polymorphic variants in the beta2-adrenergic receptor gene on
      the cardiovascular response to sympathoexcitation may have important implications
      in the development of hypertension and heart failure.

PMID- 15994242
TI  - Smooth muscle dynamics and maximal expiratory flow in asthma.
AB  - A computational model for maximal expiratory flow in constricted lungs is
      presented. The model was constructed by combining a previous computational model
      for maximal expiratory flow in normal lungs and a previous mathematical model for
      smooth muscle dynamics. Maximal expiratory flow-volume curves were computed for
      different levels of smooth muscle activation. The computed maximal expiratory
      flow-volume curves agree with data in the literature on flow in constricted
      nonasthmatic subjects. In the model, muscle force during expiration depends on
      the balance between the decrease in force that accompanies muscle shortening and
      the recovery of force that occurs during the time course of expiration, and the
      computed increase in residual volume (RV) depends on the magnitude of force
      recovery. The model was also used to calculate RV for a vital capacity maneuver
      with a slow rate of expiration, and RV was found to be further increased for this
      maneuver. We propose that the measurement of RV for a vital capacity maneuver
      with a slow rate of expiration would provide a more sensitive test of smooth
      muscle activation than the measurement of maximal expiratory flow.

PMID- 15994244
TI  - Effects of inactivity on fiber size and myonuclear number in rat soleus muscle.
AB  - The effects of short-term (4 days) and long-term (60 days) neuromuscular
      inactivity on myonuclear number, size, and myosin heavy chain (MHC) composition
      of isolated rat soleus fibers were determined using confocal microscopy and gel
      electrophoresis. Inactivity was produced via spinal cord isolation (SI), i.e.,
      complete spinal cord transections at a midthoracic and a high sacral level and
      bilateral deafferentation between the transection sites. Compared with control,
      there was an increase in the percentage of fibers containing the faster MHC
      isoforms after 60, but not 4, days of SI. The mean sizes of type I and type I+IIa
      fibers were 41 and 27% and 66 and 56% smaller after 4 and 60 days of SI,
      respectively. Thus atrophy occurred earlier than the shift in myosin heavy chain
      (MHC) profile. The number of myonuclei was approximately 30% higher in type I
      than type I+IIa fibers in control soleus, but after 60 days of SI these values
      were similar. The number of myonuclei per millimeter in type I fibers was
      significantly lower than control after 60 days of SI, whereas there was no change
      in type I+IIa fibers. Thus myonuclei were eliminated from fibers containing only
      type I MHC. Because the magnitude of the loss of myonuclei was less than the
      level of atrophy, the myonuclear domains of both type I and type I+IIa fibers
      were significantly lower than control. Thus chronic (60 days) inactivity results
      in smaller, faster fibers that contain a higher than normal amount of DNA per
      unit of cytoplasm. The absence of activation of muscle fibers that are normally
      the most active (pure type I fibers) resulted in most, but not all, fibers
      expressing some fast MHC isoforms. The results also indicate that a loss of
      myonuclei is not a prerequisite for sustained muscle fiber atrophy.

PMID- 15994243
TI  - Respiratory control stability and upper airway collapsibility in men and women
      with obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is two to three times more common in men as in
      women. The mechanisms leading to this difference are currently unclear but could
      include gender differences in respiratory stability [loop gain (LG)] or upper
      airway collapsibility [pharyngeal critical closing pressure (Pcrit)]. The aim of
      this study was to compare LG and Pcrit between men and women with OSA to
      determine whether the factors contributing to apnea are similar between genders.
      The first group of 11 men and 11 women were matched for OSA severity (mean +/- SE
      apnea-hypopnea index = 43.8 +/- 6.1 and 44.1 +/- 6.6 events/h). The second group
      of 12 men and 12 women were matched for body mass index (BMI; 31.6 +/- 1.9 and
      31.3 +/- 1.8 kg/m2, respectively). All measurements were made during stable
      supine non-rapid eye movement sleep. LG was determined using a proportional
      assist ventilator. Pcrit was measured by progressively dropping the continuous
      positive airway pressure level for three to five breaths until airway collapse.
      Apnea-hypopnea index-matched women had a higher BMI than men (38.0 +/- 2.4 vs.
      30.0 +/- 1.9 kg/m2; P = 0.03), but LG and Pcrit were similar between men and
      women (LG: 0.37 +/- 0.02 and 0.37 +/- 0.02, respectively, P = 0.92; Pcrit: 0.35
      +/- 0.62 and -0.18 +/- 0.87, respectively, P = 0.63). In the BMI-matched
      subgroup, women had less severe OSA during non-rapid eye movement sleep (30.9 +/-
      7.4 vs. 52.5 +/- 8.1 events/h; P = 0.04) and lower Pcrit (-2.01 +/- 0.62 vs. 1.16
      +/- 0.83 cmH2O; P = 0.005). However, LG was not significantly different between
      genders (0.38 +/- 0.02 vs. 0.33 +/- 0.03; P = 0.14). These results suggest that
      women may be protected from developing OSA by having a less collapsible upper
      airway for any given degree of obesity.

PMID- 15994245
TI  - Effects of eccentric exercise on microcirculation and microvascular oxygen
      pressures in rat spinotrapezius muscle.
AB  - A single bout of eccentric exercise results in muscle damage, but it is not known
      whether this is correlated with microcirculatory dysfunction. We tested the
      following hypotheses in the spinotrapezius muscle of rats either 1 (DH-1; n = 6)
      or 3 (DH-3; n = 6) days after a downhill run to exhaustion (90-120 min; -14
      degrees grade): 1) in resting muscle, capillary hemodynamics would be impaired,
      and 2) at the onset of subsequent acute concentric contractions, the decrease of
      microvascular O(2) pressure (Pmv(o(2))), which reflects the dynamic balance
      between O(2) delivery and O(2) utilization, would be accelerated compared with
      control (Con, n = 6) rats. In contrast to Con muscles, intravital microscopy
      observations revealed the presence of sarcomere disruptions in DH-1 and DH-3 and
      increased capillary diameter in DH-3 (Con: 5.2 +/- 0.1; DH-1: 5.1 +/- 0.1; DH-3:
      5.6 +/- 0.1 mum; both P < 0.05 vs. DH-3). At rest, there was a significant
      reduction in the percentage of capillaries that sustained continuous red blood
      cell (RBC) flux in both DH running groups (Con: 90.0 +/- 2.1; DH-1: 66.4 +/- 5.2;
      DH-3: 72.9 +/- 4.1%, both P < 0.05 vs. Con). Capillary tube hematocrit was
      elevated in DH-1 but reduced in DH-3 (Con: 22 +/- 2; DH-1: 28 +/- 1; DH-3: 16 +/-
      1%; all P < 0.05). Although capillary RBC flux did not differ between groups (P >
      0.05), RBC velocity was lower in DH-1 compared with Con (Con: 324 +/- 43; DH-1:
      212 +/- 30; DH-3: 266 +/- 45 mum/s; P < 0.05 DH-1 vs. Con). Baseline Pmv(O(2))
      before contractions was not different between groups (P > 0.05), but the time
      constant of the exponential fall to contracting Pmv(O(2)) values was accelerated
      in the DH running groups (Con: 14.7 +/- 1.4; DH-1: 8.9 +/- 1.4; DH-3: 8.7 +/- 1.4
      s, both P < 0.05 vs. Con). These findings are consistent with the presence of
      substantial microvascular dysfunction after downhill eccentric running, which
      slows the exercise hyperemic response at the onset of contractions and reduces
      the Pmv(O(2)) available to drive blood-muscle O(2) delivery.

PMID- 15994246
TI  - Influence of Cheyne-Stokes respiration on ventricular response to atrial
      fibrillation in heart failure.
AB  - In subjects with sinus rhythm, respiration has a profound effect on heart rate
      variability (HRV) at high frequencies (HF). Because this HF respiratory
      arrhythmia is lost in atrial fibrillation (AF), it has been assumed that
      respiration does not influence the ventricular response. However, previous
      investigations have not considered the possibility that respiration might
      influence HRV at lower frequencies. We hypothesized that Cheyne-Stokes
      respiration with central sleep apnea (CSR-CSA) would entrain HRV at very low
      frequency (VLF) in AF by modulating atrioventricular (AV) nodal refractory period
      and concealed conduction. Power spectral analysis of R-wave-to-R-wave (R-R)
      intervals and respiration during sleep were performed in 13 subjects with AF and
      CSR-CSA. As anticipated, no modulation of HRV was detected at HF during regular
      breathing. In contrast, VLF HRV was entrained by CSR-CSA [coherence between
      respiration and HRV of 0.69 (SD 0.22) at VLF during CSR-CSA vs. 0.20 (SD 0.19) at
      HF during regular breathing, P < 0.001]. Comparison of R-R intervals during CSR
      CSA demonstrated a shorter AV node refractory period during hyperpnea than apnea
      [minimum R-R of 684 (SD 126) vs. 735 ms (SD 147), P < 0.001] and a lesser degree
      of concealed conduction [scatter of 178 (SD 56) vs. 246 ms (SD 72), P = 0.001].
      We conclude that CSR-CSA entrains the ventricular response to AF, even in the
      absence of HF respiratory arrhythmia, by inducing rhythmic oscillations in AV
      node refractoriness and the degree of concealed conduction that may be a function
      of autonomic modulation of the AV node.

PMID- 15994247
TI  - Safety and antiviral activity of lopinavir/ritonavir-based therapy in human
      immunodeficiency virus type 1 (HIV-1) infection.
AB  - Protease inhibitor-based antiretroviral therapy has been shown to decrease the
      morbidity and mortality associated with human immunodeficiency virus type 1 (HIV
      1) infection. However, many of the available agents in this class suffer
      shortcomings, including poor tolerability, difficult dosing regimens, and
      variable drug concentrations which may lead to generation of viral resistance.
      Lopinavir/ritonavir (Kaletra) has been designed specifically to address some of
      these shortcomings. Excellent therapeutic efficacy has been documented for
      lopinavir/ritonavir in multiple clinical trials in both antiretroviral-naive and 
      experienced patients. Development of resistance is a rare event in persons
      initiating therapy with lopinavir/ritonavir as their first protease inhibitor.
      The main side effects associated with lopinavir/ritonavir are gastrointestinal
      disturbances and elevations of serum lipids. Current antiretroviral therapy
      guidelines list lopinavir/ritonavir as the consensus first-line protease
      inhibitor recommended in the initial therapeutic regimen in persons infected with
      HIV-1.

PMID- 15994248
TI  - Genotypic versus phenotypic characterization, with respect to susceptibility and
      identification, of 17 clinical isolates of Staphylococcus lugdunensis.
AB  - OBJECTIVES: To compare different methods for the identification and determination
      of susceptibility to penicillin and methicillin of Staphylococcus lugdunensis.
      METHODS: Seventeen clinical isolates of S. lugdunensis (identified by PCR
      amplification and sequencing of the rpoB gene) were studied using the ATB32
      Staph, Crystal, Vitek 2 and Wider commercial systems. The clumping factor test
      and the tube coagulase test were also performed. Beta-lactamase production was
      studied by chromogenic methods. Methicillin resistance was phenotypically studied
      by the MRSA slide latex agglutination test, growth in MRSA agar, and the Vitek 2
      and Wider systems (based on oxacillin MIC), and genotypically studied by
      detection of the mecA gene by PCR. RESULTS: The clumping factor test was negative
      in 35.3% of strains. All isolates were correctly identified to species level by
      the ATB32-Staph system. Species misidentification rates were 5.9%, 23.5% and
      29.4% with the Crystal, the Vitek 2 and the Wider systems, respectively, mostly
      as Staphylococcus haemolyticus. Beta-lactamase was present in 11.8% of strains.
      Whereas 76.5% and 47.1% of strains exhibited oxacillin resistance (MIC range 0.5
      2 mg/L) by the Vitek 2 system and the Wider system, respectively, none of the
      strains was positive in the MRSA slide latex agglutination test or grew in MRSA
      agar. All strains lacked the mecA gene. CONCLUSIONS: The clumping factor test and
      some commercial systems may misidentify S. lugdunensis. Oxacillin resistance
      detected by commercial systems is not indicative of the presence of the mecA
      gene. These facts, together with beta-lactamase production, may preclude adequate
      treatment of infections by this virulent coagulase-negative Staphylococcus.

PMID- 15994249
TI  - Inhibition of p38 mitogen activated protein kinase controls airway inflammation
      in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) airways are characterised by chronic
      inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation
      which are considered the principal factors of morbidity and mortality in CF
      patients. Optimising management of this chronic inflammatory response is
      therefore a key issue of basic and clinical CF research. Several reports have
      addressed ways to manage CF airways inflammation, and an attractive therapeutic
      strategy may be the inhibition of the p38-mitogen activated protein kinase (p38
      MAP-k) pathway. METHODS: A new ex vivo model was used to study the mucosal
      inflammatory response to environmental airways stimuli. Nasal biopsy tissues from
      CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24
      hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa
      (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA
      assessment, immunohistochemistry, and Western blots were used to detect the
      expression and modulation of inflammatory markers. RESULTS: PA-LPS challenge
      induced a time dependent mucosal inflammation indicated by rapid epithelial
      activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the
      upper mucosal layers. Some of these LPS induced changes (IL-8 release and
      neutrophil migration) were specific to CF tissues. SB203580 significantly
      controlled all LPS induced mucosal changes in CF tissues. CONCLUSION: These
      findings provide a rationale and proof of principle for the potential use of p38
      MAP-k inhibitors to control inflammation in patients with CF.

PMID- 15994250
TI  - Treatment of ovalbumin-induced experimental allergic bronchitis in rats by
      inhaled inhibitor of secretory phospholipase A(2).
AB  - BACKGROUND: The pathophysiology of asthma involves the action of
      inflammatory/allergic lipid mediators formed following membrane phospholipid
      hydrolysis by phospholipase A(2) (PLA(2)). Cysteinyl leukotrienes are considered
      potent inducers of bronchoconstriction and airway remodelling. Ovalbumin (OVA)
      induced bronchoconstriction in rats is associated with increased secretory PLA(2)
      (sPLA(2)) activation and cysteinyl leukotriene production, together with
      suppression of cytosolic PLA(2) and prostaglandin E(2). These processes are
      reversed when the animals are pretreated systemically with an extracellular cell
      impermeable sPLA(2) inhibitor which also suppresses the early allergic reaction
      to OVA challenge. In this study we examine the capacity of the sPLA(2) inhibitor
      to ameliorate inflammatory and allergic manifestations (early and late
      bronchoconstriction) of OVA induced allergic bronchitis in rats when the
      inhibitor was administered by inhalation to confine it to the airways. METHODS:
      Rats sensitised with OVA were treated with the sPLA(2) inhibitor hyaluronic acid
      linked phosphatidyl ethanolamine (HyPE). The rats were divided into four groups
      (n = 10 per group): (1) naive controls (no sensitisation/no treatment); (2)
      positive controls (sensitisation + challenge with OVA inhalation and subcutaneous
      injection of 1 ml saline before each challenge; (3) sensitisation + challenge
      with OVA and HyPE inhalation before every challenge; and (4) sensitisation +
      challenge with OVA and treatment with subcutaneous dexamethasone (300 mug) before
      each challenge as a conventional reference. Another group received no treatment
      with HyPE during the sensitisation process but only before or after challenge of
      already sensitised rats. Pulmonary function was assessed and changes in the
      histology of the airways, levels of cysteinyl leukotrienes in BAL fluid, and the
      production of nitric oxide (No) and tumour necrosis factor alpha (TNFalpha) by
      BAL macrophages were determined. RESULTS: Inhalation of HyPE markedly suppressed
      OVA induced early and late asthmatic reactions as expressed by
      bronchoconstriction, airway remodelling (histology), cysteinyl leukotriene level
      in BAL fluid, and production of TNFalpha and NO by BAL macrophages. OVA induced
      bronchoconstriction in sensitised non-pretreated rats was also inhibited by
      inhalation of HyPE either before or after the challenge. CONCLUSIONS: These
      findings confirm the pivotal role of sPLA(2) in the pathophysiology of both the
      immediate allergic response and the inflammatory asthmatic process. Control of
      airway sPLA(2) may be a new therapeutic approach to the treatment of asthma.

PMID- 15994251
TI  - Accuracy of transbronchial needle aspiration for mediastinal staging of non-small
      cell lung cancer: a meta-analysis.
AB  - BACKGROUND: The reported accuracy of transbronchial needle aspiration (TBNA) for
      mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We
      performed a meta-analysis to estimate the accuracy of TBNA for mediastinal
      staging in NSCLC. METHODS: Medline, Embase, and the bibliographies of retrieved
      articles were searched for studies evaluating TBNA accuracy with no language
      restriction. Meta-analytical methods were used to construct summary receiver
      operating characteristic curves and to pool sensitivity and specificity. RESULTS:
      Thirteen studies met inclusion criteria, including six studies that surgically
      confirmed all TBNA results and enrolled at least 10 patients with and without
      mediastinal metastasis (tier 1). Methodological quality varied but did not affect
      diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal
      metastasis was 34%. Using a random effects model, the pooled sensitivity and
      specificity were 39% (95% CI 17 to 61) and 99% (95% CI 96 to 100), respectively.
      Compared with tier 1 studies, the median prevalence of mediastinal metastasis
      (81%; p = 0.002) and pooled sensitivity (78%; 95% CI 71 to 84; p = 0.009) were
      higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity
      of TBNA depends critically on the prevalence of mediastinal metastasis. The
      pooled major complication rate was 0.3% (95% CI 0.01 to 4). CONCLUSIONS: When
      properly performed, TBNA is highly specific for identifying mediastinal
      metastasis in patients with NSCLC, but sensitivity depends critically on the
      study methods and patient population. In populations with a lower prevalence of
      mediastinal metastasis, the sensitivity of TBNA is much lower than reported in
      recent lung cancer guidelines.

PMID- 15994252
TI  - Effect of continuous positive airway pressure on ventricular ectopy in heart
      failure patients with obstructive sleep apnoea.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) elicits a number of cardiovascular
      perturbations that could lead acutely or chronically to increased ventricular
      ectopy in patients with heart failure (HF). We tested the hypothesis that
      treatment of OSA with continuous positive airway pressure (CPAP) in patients with
      HF would reduce the frequency of ventricular premature beats (VPBs) during sleep
      in association with reduced sympathetic nervous system activity. METHODS:
      Following optimisation of medical treatment, 18 HF patients with OSA and >10 VPBs
      per hour of sleep were randomised to a control group (n = 8) or a treatment group
      who received CPAP (n = 10). The frequency of VPBs and urinary norepinephrine
      (noradrenaline) concentrations during total sleep time were determined at
      baseline and after 1 month. RESULTS: Control patients did not experience any
      significant changes in apnoea-hypopnoea index (AHI), mean nocturnal O(2)
      saturation, or the frequency of VPBs. In contrast, there was a significant
      reduction in AHI (p<0.001), an increase in minimum O(2) saturation (p = 0.05), a
      reduction in urinary norepinephrine concentrations (p = 0.009), and a 58%
      reduction in the frequency of VPBs during total sleep (from mean (SE) 170 (65) to
      70 (28) per hour, p = 0.011) after 1 month of CPAP treatment. CONCLUSIONS: In
      patients with HF, treatment of co-existing OSA by CPAP reduces the frequency of
      VPBs during sleep. These data suggest that reductions in VPBs and other
      ventricular arrhythmias through treatment of OSA might improve the prognosis in
      patients with HF.

PMID- 15994253
TI  - Effect of salbutamol on lung function and chest wall volumes at rest and during
      exercise in COPD.
AB  - BACKGROUND: Inhaled bronchodilators can increase exercise capacity in chronic
      obstructive pulmonary disease (COPD) by reducing dynamic hyperinflation, but
      treatment is not always effective. This may reflect the degree to which the
      abdomen allows dynamic hyperinflation to occur. METHOD: A double blind,
      randomised, crossover trial of the effect of 5 mg nebulised salbutamol or saline
      on endurance exercise time was conducted in 18 patients with COPD of mean (SD)
      age 67.1 (6.3) years and mean (SD) forced expiratory volume in 1 second (FEV1) of
      40.6 (15.0)% predicted. Breathing pattern, metabolic variables, dyspnoea
      intensity, and total and regional chest wall volumes were measured non-invasively
      by optoelectronic plethysmography (OEP) at rest and during exercise. RESULTS:
      Salbutamol increased FEV1, forced vital capacity (FVC) and inspiratory capacity
      and reduced functional residual capacity (FRC) and residual volume significantly.
      OEP showed the change in resting FRC to be mainly in the abdominal compartment.
      Although the mean (SE) end expiratory chest wall volume was 541 (118) ml lower
      (p<0.001) at the end of exercise, the endurance time was unchanged by the
      bronchodilator. Changes in resting lung volumes were smaller when exercise
      duration did not improve, but FEV1 still rose significantly after active drug.
      After the bronchodilator these patients tried to reduce the end expiratory lung
      volume when exercising, while those exercising longer continued to allow end
      expiratory abdominal wall volume to rise. The change to a more euvolumic
      breathing pattern was associated with a lower oxygen pulse and a significant fall
      in endurance time with higher isotime levels of dyspnoea. CONCLUSIONS: Nebulised
      salbutamol improved forced expiratory flow in most patients with COPD, but less
      hyper-nflated patients tried to reduce the abdominal compartmental volume after
      active treatment and this reduced their exercise capacity. Identifying these
      patients has important therapeutic implications, as does an understanding of the
      mechanisms that control chest wall muscle recruitment.

PMID- 15994255
TI  - Creatine supplementation as an exercise performance enhancer for patients with
      COPD? An idea to run with.

PMID- 15994254
TI  - Exercise training and inspiratory muscle training in patients with
      bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is a chronic suppurative lung disease often
      characterised by airflow obstruction and hyperinflation, and leading to decreased
      exercise tolerance and reduced health status. The role of pulmonary
      rehabilitation (PR) and inspiratory muscle training (IMT) has not been
      investigated in this group of patients. METHODS: Thirty two patients with
      idiopathic bronchiectasis were randomly allocated to one of three groups: PR plus
      sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control. All patients
      (except the control group) underwent an 8 week training programme of either PR or
      PR plus targeted IMT. Exercise training during PR was performed three times
      weekly at 80% of the peak heart rate. IMT was performed at home for 15 minutes
      twice daily over the 8 week period. RESULTS: PR-SHAM and PR-IMT resulted in
      significant increases in the incremental shuttle walking test of 96.7 metres (95%
      confidence interval (CI) 59.6 to 133.7) and 124.5 metres (95% CI 63.2 to 185.9),
      respectively, and in endurance exercise capacity of 174.9% (95% CI 34.7 to 426.1)
      and 205.7% (95% CI 31.6 to 310.6). There were no statistically significant
      differences in the improvements in exercise between the two groups. Significant
      improvements in inspiratory muscle strength were also observed both in the PR-IMT
      group (21.4 cm H2O increase, 95% CI 9.3 to 33.4; p = 0.008) and the PR-SHAM group
      (12.0 cm H2O increase, 95% CI 1.1 to 22.9; p = 0.04), the magnitude of which were
      also similar (p = 0.220). Improvements in exercise capacity were maintained in
      the PR-IMT group 3 months after training, but not in the PR-SHAM group.
      CONCLUSION: PR is effective in improving exercise tolerance in bronchiectasis but
      there is no additional advantage of simultaneous IMT. IMT may, however, be
      important in the longevity of the training effects.

PMID- 15994256
TI  - Smoking and tuberculosis: a chance or causal association?

PMID- 15994257
TI  - Is the neutrophil the key effector cell in severe asthma?

PMID- 15994258
TI  - Creatine supplementation during pulmonary rehabilitation in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Skeletal muscle wasting and dysfunction are strong independent
      predictors of mortality in patients with chronic obstructive pulmonary disease
      (COPD). Creatine nutritional supplementation produces increased muscle mass and
      exercise performance in health. A controlled study was performed to look for
      similar effects in 38 patients with COPD. METHODS: Thirty eight patients with
      COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted)
      were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine
      monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2
      weeks loading (one dose three times daily), patients participated in an
      outpatient pulmonary rehabilitation programme combined with maintenance (once
      daily) supplementation. Pulmonary function, body composition, and exercise
      performance (peripheral muscle strength and endurance, shuttle walking, cycle
      ergometry) took place at baseline (n = 38), post loading (n = 36), and post
      rehabilitation (n = 25). RESULTS: No difference was found in whole body exercise
      performance between the groups: for example, incremental shuttle walk distance
      mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to
      47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI
      0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation.
      Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI
      1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee
      extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI
      131.3 to 1577.4) post rehabilitation. Creatine improved health status between
      baseline and post rehabilitation (St George's Respiratory Questionnaire total
      score -7.7 (95% CI -14.9 to -0.5)). CONCLUSIONS: Creatine supplementation led to
      increases in fat-free mass, peripheral muscle strength and endurance, health
      status, but not exercise capacity. Creatine may constitute a new ergogenic
      treatment in COPD.

PMID- 15994259
TI  - Systemic inflammation in COPD visualised by gene profiling in peripheral blood
      neutrophils.
AB  - BACKGROUND: The inflammatory process in chronic obstructive pulmonary disease
      (COPD) is characterised by the presence of neutrophils in the lung that are able
      to synthesise de novo several inflammatory mediators. The local chronic
      persistent inflammatory response is accompanied by systemic effects such as
      cytokine induced priming of peripheral leucocytes and muscle wasting. The
      preactivation or priming of peripheral blood neutrophils was used to gain more
      insight into the mechanisms of this systemic inflammatory response. METHODS: Gene
      arrays were performed on peripheral blood neutrophils obtained from healthy
      donors after stimulation in vitro with tumour necrosis factor (TNF)-alpha,
      granulocyte-macrophage colony stimulating factor (GM-CSF), or both. The
      expression of many inflammatory genes was regulated in these cells following
      stimulation. The expression of inflammatory genes in peripheral blood neutrophils
      in healthy subjects and those with COPD was measured by real time RT-PCR after
      stimulation with TNFalpha, GM-CSF, interleukin (IL)-8, fMLP, TNFalpha + GM-CSF,
      and lipopolysaccharide (LPS). RESULTS: The genes regulated in the gene array with
      TNFalpha/GM-CSF stimulated neutrophils included cytokines (such as IL-1beta),
      chemokines (such as IL-8), and adhesion molecules (such as ICAM-1). Disease
      severity as measured by forced expiratory volume in 1 second (FEV(1)) in COPD
      patients correlated with expression of several of these genes including IL-1beta
      (r = -0.540; p = 0.008), MIP-1beta (r = -0.583; p = 0.003), CD83 (r = -0.514; p =
      0.012), IL-1 receptor 2 (r = -0.546; p = 0.007), and IL-1 receptor antagonist (r
      = -0.612; p = 0.002). CONCLUSIONS: These data are consistent with the hypothesis
      that progression of COPD is associated with the activation of neutrophils in the
      systemic compartment. De novo expression of inflammatory mediators by peripheral
      blood neutrophils suggests a pro-inflammatory role for these cells in the
      pathogenesis of COPD.

PMID- 15994260
TI  - No increase in the prevalence of asthma, allergies, and atopic sensitisation
      among children in Germany: 1992-2001.
AB  - BACKGROUND: From 1970 to 1990 increasing rates of asthma and allergic
      sensitisation were observed in several countries. The aim of this study was to
      investigate time trends in the prevalence of asthma and allergic sensitisation
      among school children in Germany between 1992 and 2001. METHODS: Parental reports
      of asthma, hay fever, and wheezing and measurements of specific serum IgE
      antibodies were investigated in six serial cross sectional surveys of 9-11 year
      old school children in three study areas in south west Germany. RESULTS: A total
      of 6762 school children of mean age 10 years (mean participation rate 77.9%) took
      part in the investigation in the three study areas. Over the 9 year study period
      no increase in the prevalence of current wheezing and asthma was observed. In
      addition, the prevalence of atopic sensitisation remained unchanged during the
      observation period. CONCLUSIONS: These data, using parental reports and objective
      measures of allergy, suggest that there has been no further increase in the
      prevalence of asthma and atopy since 1992. The epidemic may thus have reached a
      plateau.

PMID- 15994261
TI  - The early origins hypothesis with an emphasis on growth rate in the first year of
      life and asthma: a prospective study in Chile.
AB  - BACKGROUND: There is uncertainty about the impact of the programming hypothesis
      in terms of nutritional status at birth, rate of growth in the first year of
      life, length of gestation, breast feeding, and episodes of illness on asthma. An
      analysis was therefore carried out to test this hypothesis. METHODS: Data were
      collected on 1232 children born between 1974 and 1978 in a semi-rural area of
      Chile. Measurements at birth and growth in the first year of life were obtained
      from a birth registry and clinical notes. Information on asthma was collected
      using the European Community Respiratory Health Survey questionnaire.
      Sensitisation to eight allergens and bronchial hyperresponsiveness (BHR) to
      methacholine were determined. All other information was obtained using a
      questionnaire. Polytomous logistic analyses were carried out to explore the
      association of factors at birth and during the first year of life with asthma
      symptoms, atopy, and BHR. RESULTS: Weight and length gain in the first year were
      positively associated with wheeze (odds ratio (OR) 1.004, 95% CI 1.001 to 1.007
      and OR 1.11, 95% CI 0.98 to 1.25, respectively). A higher body mass index (BMI)
      at birth was protective in subjects reporting both wheeze and waking with
      breathlessness (OR 0.54, 95% CI 0.35 to 0.84). Length rate in tertiles divided by
      length at birth in tertiles was related to asthma symptoms (OR 1.68, 95% CI 1.19
      to 2.37). Most other assessments were not associated with asthma. CONCLUSION:
      These results show promising but inconclusive evidence that a rapid rate of
      growth in length, especially in newborn infants of low length, might be involved
      in the aetiology of asthma.

PMID- 15994262
TI  - Association between smoking and tuberculosis infection: a population survey in a
      high tuberculosis incidence area.
AB  - BACKGROUND: Associations between smoking and tuberculosis disease including death
      from tuberculosis have been reported, but there are few reports on the influence
      of smoking on the risk of developing Mycobacterium tuberculosis infection. The
      aim of this study was to determine the association between smoking and M
      tuberculosis infection. METHODS: In a cross sectional population survey, data on
      smoking and tuberculin skin test (TST) results of 2401 adults aged > or =15 years
      were compared. RESULTS: A total of 1832 (76%) subjects had a positive TST (> or =
      10 mm induration). Of 1309 current smokers or ex-smokers, 1070 (82%) had a
      positive TST. This was significantly higher than for never smokers (unadjusted OR
      1.99, 95% confidence interval (CI) 1.62 to 2.45). A positive relationship with
      pack-years was observed, with those smoking more than 15 pack-years having the
      highest risk (adjusted OR 1.90, 95% CI 1.28 to 2.81). CONCLUSION: Smoking may
      increase the risk of M tuberculosis infection.

PMID- 15994263
TI  - Genotype-phenotype correlation for pulmonary function in cystic fibrosis.
AB  - BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been
      identified. To date, a clear relationship has not been established between
      genotype and the progression of lung damage. A study was undertaken of the
      relationship between genotype, progression of lung disease, and survival in adult
      patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult
      patients with CF and two CFTR mutations followed up in an adult cystic fibrosis
      unit was analysed. Patients were classified according to functional effects of
      classes of CFTR mutations and were grouped based on the CFTR molecular position
      on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values,
      progression of lung disease, probability of survival, and clinical
      characteristics were analysed between groups. RESULTS: Seventy four patients were
      included in the study. Patients with genotype I-II/I-II had significantly lower
      current spirometric values (p < 0.001), greater loss of pulmonary function (p <
      0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk
      of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to
      40.5)) and a lower probability of survival than patients with genotype I-II/III,
      I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II
      mutations on both chromosomes is associated with worse respiratory disease and a
      lower probability of survival.

PMID- 15994264
TI  - Estimation of the additional costs of chemotherapy for patients with advanced non
      small cell lung cancer.
AB  - BACKGROUND: A large multicentre randomised trial, the Big Lung Trial, which in
      part compared supportive care with or without cisplatin-based chemotherapy in
      patients with advanced non-small cell lung cancer, provided an opportunity to
      evaluate the impact on the UK National Health Service of the costs incurred with
      the use of chemotherapy. METHODS: This costing study was based on the
      retrospective collection of resource use data from hospital records. Case notes
      from 194 patients (98 chemotherapy + supportive care (C), 96 supportive care
      alone (NoC)) were inspected in eight centres recruiting the largest numbers of
      patients into the Big Lung Trial. Quantities were multiplied by fixed unit costs
      to calculate a total cost for each patient. The main outcome measure was the
      total cost incurred by the use of secondary care resources (including
      investigations, chemotherapy, radiotherapy, surgical procedures, inpatient days,
      outpatient attendances, and hospice inpatient care) in the two groups. RESULTS:
      Patients randomised to receive cisplatin-based chemotherapy had an average of 3.4
      more inpatient bed days than the mean of 11.9 days for patients randomised to
      supportive care alone, and more outpatient attendances. NoC patients were more
      likely to have received palliative radiotherapy. The mean total cost for C
      patients was 5355 sterling pound compared with 3595 sterling pound for the NoC
      group, difference 760 sterling pound (95% CI 781 sterling pound to 2742 sterling
      pound ). When split, the cost in the C group associated with the administration
      of chemotherapy was 1233 sterling pound and non-chemotherapy costs were 4122
      sterling pound . CONCLUSION: The additional cost of chemotherapy was not offset
      by a reduction in subsequent costs (as the non-chemotherapy costs were similar),
      so the survival benefit of about 10 weeks observed in the C group was achieved
      with the cost of chemotherapy administration.

PMID- 15994265
TI  - Relationship between reduced forced expiratory volume in one second and the risk
      of lung cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Individuals with severely impaired lung function have an increased
      risk of lung cancer. Whether milder reductions in forced expiratory volume in 1
      second (FEV(1)) also increase the risk of lung cancer is controversial. Moreover,
      there is little consensus on whether men and women have similar risks for lung
      cancer for similar decreases in FEV(1). METHODS: A search was conducted of PubMed
      and EMBASE from January 1966 to January 2005 and studies that examined the
      relationship between FEV1 and lung cancer were identified. The search was limited
      to studies that were population based, employed a prospective design, were large
      in size (> or = 5000 participants), and adjusted for cigarette smoking status.
      RESULTS: Twenty eight abstracts were identified, six of which did not report FEV1
      and eight did not adjust for smoking. Included in this report are four studies
      that reported FEV1 in quintiles. The risk of lung cancer increased with
      decreasing FEV1. Compared with the highest quintile of FEV1 (> 100% of
      predicted), the lowest quintile of FEV1 (< approximately 70% of predicted) was
      associated with a 2.23 fold (95% confidence interval (CI) 1.73 to 2.86) increase
      in the risk for lung cancer in men and a 3.97 fold increase in women (95% CI 1.93
      to 8.25). Even relatively small decrements in FEV1 ( approximately 90% of
      predicted) increased the risk for lung cancer by 30% in men (95% CI 1.05 to 1.62)
      and 2.64 fold in women (95% CI 1.30 to 5.31). CONCLUSION: Reduced FEV1 is
      strongly associated with lung cancer. Even a relatively modest reduction in FEV1
      is a significant predictor of lung cancer, especially among women.

PMID- 15994266
TI  - Differential expression of VASP in normal lung tissue and lung adenocarcinomas.
AB  - BACKGROUND: Vasodilator stimulated phosphoprotein (VASP) is associated with focal
      adhesions and is thought to have an important role in actin filament assembly and
      cell motility. We hypothesise that an increase in the expression of VASP is
      involved in the progression and invasion of lung adenocarcinomas in parallel to
      tumour progression. A study was undertaken to analyse VASP expression in normal
      lung tissue and lung adenocarcinomas. METHODS: Human lung tissues with
      adenocarcinomas (n = 26) were used. Normal lung tissue specimens (n = 14) were
      taken from areas a standard distance (3 cm) from resected adenocarcinomas of
      patients who underwent surgical lung resection. Adenocarcinomas were classified
      according to pathological staging and histopathological grades. Tissues were
      stained for VASP using immunohistochemistry. RESULTS: Normal lung pneumocytes
      showed no VASP expression while alveolar macrophages had the strongest
      immunoreactivity for VASP. Bronchial epithelium (surface epithelium, goblet
      cells) and bronchial gland cells had a very weak immunoreactivity for VASP.
      Adenocarcinomas had significantly greater VASP expression than normal epithelium
      (p < 0.001). Moreover, VASP expression in adenocarcinomas increased significantly
      with more advanced tumour stage (p < 0.001). CONCLUSIONS: The spatial and
      differential expression of VASP in normal lung tissue and lung adenocarcinomas
      suggests that it is likely to be involved in the differentiation of normal lung
      cells to adenocarcinomas. The significant increase in the expression of VASP in
      adenocarcinomas in parallel to pathological staging suggests that it may regulate
      the invasive behaviour of lung adenocarcinomas as adenocarcinoma invasion is
      increased in more advanced tumours.

PMID- 15994267
TI  - Recovery of the ciliated epithelium following acute bronchiolitis in infancy.
AB  - BACKGROUND: Little is known about the longitudinal changes in the ciliated
      respiratory epithelium of infants following viral bronchiolitis. A study was
      undertaken to investigate the time required for the ciliated epithelium to return
      to normal following bronchiolitis in infants treated with inhaled steroids or
      placebo. METHODS: Thirty one previously healthy term infants were studied as part
      of a clinical trial to determine the effect of 12 weeks of treatment with inhaled
      fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen
      healthy children aged 0-6 years previously studied in our department were used as
      controls. Nasal biopsy specimens were taken from infants with bronchiolitis and
      ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12,
      and 24 weeks later. The epithelial ultrastructure was examined by transmission
      electron microscopy and a normal errors mixed model based on normal controls was
      used to examine the time for cilia to return to normal in bronchiolitic infants.
      RESULTS: The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12,
      and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n =
      7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n =
      4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure
      to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated
      cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities
      in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no
      significant effects on CBF or epithelial ultrastructure. CONCLUSION: Ciliary loss
      and epithelial abnormalities persist on average for 13-17 weeks following acute
      bronchiolitis in infancy.

PMID- 15994268
TI  - Health-related quality of life in patients with idiopathic pulmonary fibrosis: a
      systematic review.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) profoundly affects the quality of
      patients' lives. A systematic review was performed to evaluate critically the
      published literature and to examine what is known about health-related quality of
      life (HRQL) in patients with IPF. METHODS: The MEDLINE, EMBASE, Health and
      Psychosocial Instruments, and Cochrane Library databases were searched to 1 April
      2004. Abstracts and bibliographies of published articles were scanned and contact
      was made with investigators. Included studies analysed HRQL (or quality of life)
      in at least 10 patients with IPF. Two reviewers independently selected studies,
      evaluated their quality according to predetermined criteria, and abstracted data
      on study design, patients' demographic and clinical characteristics, and quality
      of life outcome measures. RESULTS: Seven studies met the inclusion criteria. The
      studies enrolled 512 patients with IPF and used three different instruments to
      measure HRQL. All studies had important limitations in methodological quality;
      none measured longitudinal changes in HRQL over time. Patients reported
      substantially impaired HRQL, especially in domains that measured physical health
      and level of independence. Patients with IPF appear to have similar impairments
      in HRQL to those with chronic obstructive pulmonary disease. Measures of dyspnoea
      were moderately correlated with scores from domains that measured physical health
      (R2 = 0.03-0.66) and energy/fatigue/pep (R2 = 0.19-0.55), but measures of
      pulmonary function and gas exchange did not correlate as strongly with these and
      other domains. CONCLUSION: Studies of HRQL in patients with IPF suggest that, in
      addition to the obvious effect on physical health, general health, energy level,
      respiratory symptoms, and level of independence are also impaired. Variability in
      HRQL among patients is not fully explained by measures of dyspnoea or pulmonary
      function, suggesting that HRQL measures provide unique information. More research
      is needed to identify or design appropriate measurement instruments for patients
      with IPF and to examine changes in HRQL over time or in response to specific
      treatments.

PMID- 15994270
TI  - Pulmonary hypertension in chronic obstructive pulmonary disease: current theories
      of pathogenesis and their implications for treatment.
AB  - The development of pulmonary hypertension is a poor prognostic sign in patients
      with chronic obstructive pulmonary disease (COPD), affecting both mortality and
      quality of life. Although pulmonary hypertension in COPD is traditionally viewed
      as a result of emphysematous destruction of the vascular bed and/or hypoxia,
      recent studies indicate that neither of these factors correlates very well with
      pulmonary artery pressures. New human and animal experimental data are beginning
      to show that pulmonary hypertension in this setting is probably a result of the
      direct effect of tobacco smoke on the intrapulmonary vessels with abnormal
      production of mediators that control vasoconstriction, vasodilatation, and
      vascular cell proliferation, ultimately leading to aberrant vascular remodelling
      and aberrant vascular physiology. These changes are in many ways similar to those
      seen in other forms of pulmonary hypertension and suggest that the treatments
      used for primary pulmonary hypertension may be beneficial in patients with COPD.

PMID- 15994269
TI  - Sleep x 9: an approach to treatment of obstructive sleep apnoea/hypopnoea
      syndrome including upper airway surgery.
AB  - This article provides an overview of the management of the obstructive sleep
      apnoea/hypopnoea syndrome (OSAHS). Where possible, recommendations are based on a
      review of the relevant literature. With the exception of nasal continuous
      positive airway pressure, which is considered in greater detail elsewhere in the
      series, and certain oral appliances, the efficacy of many proposed treatments for
      OSAHS is not supported by data from randomised controlled clinical trials. To a
      considerable extent, treatment recommendations are based on data from
      uncontrolled studies, case series, consensus guidelines, practice parameters, and
      other less rigorous forms of evidence.

PMID- 15994271
TI  - Increased disease activity in a patient with sarcoidosis after high dose
      interleukin 2 treatment for metastatic renal cancer.
AB  - Sarcoidosis is a disease of unknown aetiology in which cytokines such as
      interleukin 2 (IL-2) are thought to play an important role. We present the case
      history of a 48 year old man with sarcoidosis who received treatment with high
      dose IL-2 for metastatic renal cell cancer, following which he developed
      hypercalcaemia characterised by a raised level of 1,25-dihydroxyvitamin D (1,25
      (OH)2-D3), a finding consistent with sarcoidosis associated hypercalcaemia. The
      increased activity in his sarcoidosis following IL-2 treatment provides direct
      supportive evidence for the role of IL-2 in the pathogenesis of sarcoidosis.

PMID- 15994272
TI  - COPD, restrictive syndrome and inflammation.

PMID- 15994273
TI  - Risedronate induced BOOP complicated with sarcoidosis.

PMID- 15994274
TI  - TB screening and anti-TNF alpha treatment.

PMID- 15994275
TI  - Exhaled NO in diffuse alveolar haemorrhage.

PMID- 15994276
TI  - Bacterial denitrification, nitric oxide and airway pH in CF.

PMID- 15994277
TI  - Sternal fracture with fatal outcome in cystic fibrosis.

PMID- 15994278
TI  - Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of
      the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to
      durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats
      to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects
      of >95% O2. The objective of this study was to examine whether exposure of adult
      rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ
      reduction on passage through the lung. We measured DQH2 appearance in the venous
      effluent during DQ infusion at different concentrations into the pulmonary artery
      of isolated perfused lungs from rats exposed to room air or to 85% O2. We also
      evaluated the effect of hyperoxia on vascular transit time distribution and
      measured NQO1 activity and protein in lung homogenate. The results demonstrate
      that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2
      and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs.
      Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum
      rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant
      for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase
      in NQO1 activity of lung cells accessible to DQ from the vascular region,
      consistent qualitatively but not quantitatively with an increase in lung
      homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be
      accounted for by approximately 40% increase in vascular transit time
      heterogeneity in 21-day hyperoxic lungs.

PMID- 15994279
TI  - Minor physical anomalies are not increased in the offspring of mothers with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the incidence and type of minor physical anomalies (MPAs)
      in infants born to mothers with systemic lupus erythematosus (SLE). METHODS: Each
      trimester, pregnant women with SLE were assessed for disease activity, prescribed
      drug use, and exposure to tobacco, alcohol, and illicit drugs through a self
      reported questionnaire. Infant examinations were performed on 30/39 (77%) live
      births in women with SLE and the incidence of MPAs determined. RESULTS: 2/30 (7%)
      patients had three or more MPAs; 4 (13%) had two; 7 (23%) had one; and 17 (57%)
      had none. One in three women reported alcohol, tobacco, and illicit drug use.
      Facial anomalies were the most common MPAs. The relative risk and 95% confidence
      interval for any MPA were 2.05 (0.99 to 4.26) for tobacco use; 1.95 (0.92 to
      4.11) for alcohol use; 1.36 (0.165 to 11.23) for maternal disease flare; 0.63
      (0.27 to 1.47) for prednisone use; and 0.72 (0.21 to 2.44) for aspirin use.
      CONCLUSION: 13/30 (43%) infants had minor anomalies-a similar incidence to that
      of the general population. Counselling for preventable self reported exposure is
      advisable in addition to counselling specifically for lupus management during
      pregnancy.

PMID- 15994280
TI  - Clinical practice decision tree for the choice of the first disease modifying
      antirheumatic drug for very early rheumatoid arthritis: a 2004 proposal of the
      French Society of Rheumatology.
AB  - OBJECTIVE: To elaborate a clinical practice decision tree for the choice of the
      first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid
      arthritis of less than six months' duration. METHODS: Four steps were employed:
      (1) review of published reports on DMARD efficacy against rheumatoid arthritis;
      (2) inventory of the information available to guide DMARD choice; (3) selection
      of the most pertinent information by 12 experts using a Delphi method; and (4)
      choice of DMARDs in 12 clinical situations defined by items selected in step 3
      (28 joint disease activity score (DAS 28): < or =3.2; >3.2 and < or =5.1; >5.1;
      rheumatoid factor status (positive/negative); structural damage (with/without)
      that is, 3 x 2 x 2). Thus, multiplied by all the possible treatment pairs, 180
      scenarios were obtained and presented to 36 experts, who ranked treatment choices
      according to the Thurstone pairwise method. RESULTS: Among the 77 items
      identified, 41 were selected as pertinent to guide the DMARD choice. They were
      reorganised into five domains: rheumatoid arthritis activity, factors predictive
      of structural damage; patient characteristics; DMARD characteristics; physician
      characteristics. In the majority of situations, the two top ranking DMARD choices
      were methotrexate and leflunomide. Etanercept was an alternative for these agents
      when high disease activity was associated with poor structural prognosis and
      rheumatoid factor positivity. CONCLUSIONS: Starting with simple scenarios and
      using the pairwise method, a clinical decision tree could be devised for the
      choice of the first DMARD to treat very early rheumatoid arthritis.

PMID- 15994281
TI  - Growing up and moving on. A multicentre UK audit of the transfer of adolescents
      with juvenile idiopathic arthritis from paediatric to adult centred care.
AB  - OBJECTIVE: To assess the provisions made for the transfer of adolescents with
      juvenile idiopathic arthritis to adult rheumatology clinics in the UK and the
      impact of a transitional care programme. METHODS: An audit of the documentation
      of the provisions made for transfer in 10 centres participating in a controlled
      trial of transitional care. Each centre conducted a retrospective case note audit
      of the recent patients transferred to adult care before and 12-24 months after
      the start of the trial. Demographic details, age when transition was first
      discussed, age at transfer, transitional issues, multidisciplinary team
      involvement, adolescent self advocacy, and readiness were documented. RESULTS:
      There were improvements at follow up in documentation of transitional issues,
      disease specific educational needs, adolescent readiness, and parental needs with
      the exception of dental care, dietary calcium, and home exercise programmes. The
      age at which the concept of an independent clinic visit was introduced was lower
      (mean (SD): 16.8 (1.06) v 15.8 (1.46) years, p = 0.01) but there were no other
      changes in age related transitional milestones. Significantly more participants
      had preparatory visits to the adult clinic, had a transition plan, and had joint
      injections while awake at follow up. CONCLUSIONS: The improvement in
      documentation suggests that involvement in the research project increased
      awareness of transitional issues. The difficulty of changing policy into practice
      was highlighted, with room for improvement, particularly at the paediatric/adult
      interface. The reasons for this are likely to be multiple, including resources
      and lack of specific training.

PMID- 15994282
TI  - Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool
      for risk assessment before allogeneic HCT.
AB  - We previously reported that the Charlson Comorbidity Index (CCI) was useful for
      predicting outcomes in patients undergoing allogeneic hematopoietic cell
      transplantation (HCT). However, the sample size of patients with scores of 1 or
      more, captured by the CCI, did not exceed 35%. Further, some comorbidities were
      rarely found among patients who underwent HCT. Therefore, the current study was
      designed to (1) better define previously identified comorbidities using
      pretransplant laboratory data, (2) investigate additional HCT-related
      comorbidities, and (3) establish comorbidity scores that were suited for HCT.
      Data were collected from 1055 patients, and then randomly divided into training
      and validation sets. Weights were assigned to individual comorbidities according
      to their prognostic significance in Cox proportional hazard models. The new index
      was then validated. The new index proved to be more sensitive than the CCI since
      it captured 62% of patients with scores more than 0 compared with 12%,
      respectively. Further, the new index showed better survival prediction than the
      CCI (likelihood ratio of 23.7 versus 7.1 and c statistics of 0.661 versus 0.561,
      respectively, P < .001). In conclusion, the new simple index provided valid and
      reliable scoring of pretransplant comorbidities that predicted nonrelapse
      mortality and survival. This index will be useful for clinical trials and patient
      counseling before HCT.

PMID- 15994283
TI  - Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel
      strategy with potential in clinical immunosuppression.
AB  - Activation of T lymphocytes requires the recognition of peptide-major
      histocompatibility complexes (MHCs) and costimulatory signals provided by antigen
      presenting cells (APCs). It has been shown that T-cell activation without
      costimulation can lead to anergy. In this study, we developed a novel strategy to
      inhibit expression of B7 molecules (CD80/86) by transfecting APCs with a gene
      construct encoding a modified cytotoxic T lymphocyte antigen 4 (CTLA4) molecule
      (CTLA4-KDEL) that is targeted to the endoplasmic reticulum (ER). APCs expressing
      this construct failed to express CD80/86 on their surface, were unable to
      stimulate allogeneic and peptide-specific T-cell responses, and induced antigen
      specific anergy of the responding T cells. Cells expressing CTLA4-KDEL do not up
      regulate the indoleamine 2, 3-dioxygenase enzyme, unlike cells treated with
      soluble CTLA4-immunoglobin (Ig). This gene-based strategy to knock out surface
      receptors is an attractive alternative to using immature dendritic cells for
      preventing transplant rejection and treating of autoimmune diseases.

PMID- 15994284
TI  - In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral
      vectors.
AB  - Hematopoietic stem cell (HSC) gene transfer has been attempted almost entirely ex
      vivo and has been limited by cytokine-induced loss of self-renewal capacity and
      transplantation-related defects in homing and engraftment. Here, we attempted to
      circumvent such limitations by injecting vectors directly into the bone marrow
      (BM) to transduce HSCs in their native environment. Simian virus 40 (SV40)
      derived gene delivery vectors were used because they transduce resting CD34+
      cells very efficiently. Rats received SV-(Nef-FLAG), carrying FLAG marker epitope
      -or a control recombinant SV40 (rSV40)--directly into both femoral marrow
      cavities. Intracellular transgene expression by peripheral blood (PB) or BM cells
      was detected by cytofluorimetry. An average of 5.3% PB leukocytes expressed FLAG
      for the entire study--56 weeks. Transgene expression was sustained in multiple
      cell lineages, including granulocytes (average, 3.3% of leukocytes, 20.4% of
      granulocytes), CD3+ T lymphocytes (average, 0.53% of leukocytes, 1% of total T
      cells), and CD45R+ B lymphocytes, indicating gene transfer to long-lived
      progenitor cells with multilineage capacity. An average of 15% of femoral marrow
      cells expressed FLAG up to 16.5 months after transduction. Thus, direct
      intramarrow administration of rSV40s yields efficient gene transfer to rat BM
      progenitor cells and may be worthy of further investigation.

PMID- 15994285
TI  - Clinical characteristics and prognostic implications of NPM1 mutations in acute
      myeloid leukemia.
AB  - Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the
      subcellular localization of the product, have been reported in acute myeloid
      leukemia (AML). We analyzed the clinical significance of NPM1 mutations in
      comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial
      tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found
      NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%)
      patients. NPM1 mutations were associated with normal karyotype and with internal
      tandem duplication (ITD) and D835 mutations in FLT3, but not with other
      mutations. In 190 patients without the M3 French-American-British (FAB) subtype
      who were treated with the protocol of the Japan Adult Leukemia Study Group,
      multivariate analyses showed that the NPM1 mutation was a favorable factor for
      achieving complete remission but was associated with a high relapse rate.
      Sequential analysis using 39 paired samples obtained at diagnosis and relapse
      showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had
      NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not
      necessarily an early event during leukemogenesis or that leukemia clones with
      NPM1 mutations are sensitive to chemotherapy.

PMID- 15994286
TI  - Directing thrombin.
AB  - Following initiation of coagulation as part of the hemostatic response to injury,
      thrombin is generated from its inactive precursor prothrombin by factor Xa as
      part of the prothrombinase complex. Thrombin then has multiple roles. The way in
      which thrombin interacts with its many substrates has been carefully scrutinized
      in the past decades, but until recently there has been little consideration of
      how its many functions are coordinated or directed. Any understanding of how it
      is directed requires knowledge of its structure, how it interacts with its
      substrates, and the role of any cofactors for its interaction with substrates.
      Recently, many of the interactions of thrombin have been clarified by crystal
      structure and site-directed mutagenesis analyses. These analyses have revealed
      common residues used for recognition of some substrates and overlapping surface
      exosites used for recognition by cofactors. As many of its downstream reactions
      are cofactor driven, competition between cofactors for exosites must be a
      dominant mechanism that determines the fate of thrombin. This review draws
      together much recent work that has helped clarify structure function
      relationships of thrombin. It then attempts to provide a cogent proposal to
      explain how thrombin activity is directed during the hemostatic response.

PMID- 15994287
TI  - Response criteria for myelofibrosis with myeloid metaplasia: results of an
      initiative of the European Myelofibrosis Network (EUMNET).
AB  - The European Myelofibrosis Network (EUMNET), a European research network on
      myelofibrosis with myeloid metaplasia (MMM), has developed a definition of
      response for the disease by using clinicohematologic, histologic, and cytogenetic
      criteria. A core set of 5 clinicohematologic criteria was selected out of 9
      candidates on the basis of their sensitivity to change measured in 196 patients
      treated either during clinical trials or routine clinical practice. A consensus
      panel of 16 international experts was convened and asked to score the level of
      response in 104 patient profiles as major, moderate, minor, or no response
      according to changes of the clinicohematologic criteria. Using the experts'
      consensus as the gold standard, the performance of 100 possible definitions of
      response was evaluated. Criteria for major or moderate clinicohematologic
      response were determined to be changes in hemoglobin (Hb) and spleen size and the
      presence of constitutional symptoms, while changes in platelet count and white
      blood cell (WBC) count served as complementary criteria and were of value for
      defining minor responses. A histologic response was defined by changes in bone
      marrow fibrosis and cellularity grades. The combined use of these response
      definitions should help standardize the design and reporting of future clinical
      studies in MMM.

PMID- 15994288
TI  - The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and
      cytarabine in the treatment of elderly patients with previously untreated acute
      myeloid leukemia (AML), in relation to MDR1 status at diagnosis.
AB  - To determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp)
      inhibitor PSC-833 to standard induction chemotherapy would improve event-free
      survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60
      years and older were randomized to receive 2 induction cycles of daunorubicin and
      cytarabine with or without PSC-833. Patients in complete remission were then
      given 1 consolidation cycle without PSC-833. Neither complete response (CR) rate
      (54% versus 48%; P = .22), 5-year EFS (7% versus 8%; P = .53), disease-free
      survival (DFS; 13% versus 17%; P = .06) nor overall survival (OS; 10% in both
      arms; P = .52) were significantly improved in the PSC-833 arm. An integrated P-gp
      score (IPS) was determined based on P-gp function and P-gp expression in AML
      cells obtained prior to treatment. A higher IPS was associated with a
      significantly lower CR rate and worse EFS and OS. There was no significant
      interaction between IPS and treatment arm with respect to CR rate and survival,
      indicating also a lack of benefit of PSC-833 in P-gp-positive patients. The role
      of strategies aimed at inhibitory P-gp and other drug-resistance mechanisms
      continues to be defined in the treatment of patients with AML.

PMID- 15994289
TI  - nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the
      mouse.
AB  - Hypochromic, microcytic anemias are typically the result of inadequate hemoglobin
      production because of globin defects or iron deficiency. Here, we describe the
      phenotypic characteristics and pathogenesis of a new recessive, hypochromic,
      microcytic anemia mouse mutant, nm1054. Although the mutation nm1054 is
      pleiotropic, also resulting in sparse hair, male infertility, failure to thrive,
      and hydrocephaly, the anemia is the focus of this study. Hematologic analysis
      reveals a moderately severe, congenital, hypochromic, microcytic anemia, with an
      elevated red cell zinc protoporphyrin, consistent with functional erythroid iron
      deficiency. However, serum and tissue iron analyses show that nm1054 animals are
      not systemically iron deficient. From hematopoietic stem cell transplantation and
      iron uptake studies in nm1054 reticulocytes, we provide evidence that the nm1054
      anemia is due to an intrinsic hematopoietic defect resulting in inefficient
      transferrin-dependent iron uptake by erythroid precursors. Linkage studies
      demonstrate that nm1054 maps to a genetic locus not previously implicated in
      microcytic anemia or iron phenotypes.

PMID- 15994290
TI  - Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in
      endothelial cells.
AB  - Transcriptional control has been identified as a key mechanism regulating the
      formation and subsequent behavior of hematopoietic stem cells. We have used a
      comparative genomics approach to identify transcriptional regulatory elements of
      the LMO2 gene, a transcriptional cofactor originally identified through its
      involvement in T-cell leukemia and subsequently shown to be critical for normal
      hematopoietic and endothelial development. Of the 2 previously characterized LMO2
      promoters, the second (proximal) promoter was highly conserved in vertebrates
      ranging from mammals to fish. Real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) expression analysis identified this promoter as the predominant
      source of transcription in hematopoietic tissue. Transient and stable
      transfections indicated that the proximal promoter was active in hematopoietic
      progenitor and endothelial cell lines and this activity was shown to depend on 3
      conserved Ets sites that were bound in vivo by E74-like factor 1 (Elf1), Friend
      leukemia integration 1 (Fli1), and erythroblastosis virus oncogene homolog E
      twenty-six-1 (Ets1). Finally, transgenic analysis demonstrated that the LMO2
      proximal promoter is sufficient for expression in endothelial cells in vivo. No
      hematopoietic expression was observed, indicating that additional enhancers are
      required to mediate transcription from the proximal promoter in hematopoietic
      cells. Together, these results suggest that the conserved proximal promoter is
      central to LMO2 transcription in hematopoietic and endothelial cells, where it is
      regulated by Ets factors.

PMID- 15994291
TI  - Differential effect of agonistic anti-CD40 on human mature and immature dendritic
      cells: the Janus face of anti-CD40.
AB  - Agonistic monoclonal antibodies to CD40 (CD40 mAbs) have a puzzling dual
      therapeutic effect in experimental animal models. CD40 mAbs induce tumor
      regression by potentiating antitumoral T-cell responses, yet they also have
      immunosuppressive activity in chronic autoimmune inflammatory processes. CD40
      mAbs are thought to act on antigen presentation by dendritic cells (DCs) to T
      cells. DCs can be distinguished as either immature or mature by their phenotype
      and their ability to generate an effective T-cell response. Here we found that,
      on human cells, although anti-CD40 led immature DCs to mature and became
      immunogenic, it also reduced the capacity of lipopolysaccharide (LPS) and tumor
      necrosis factor alpha (TNF-alpha)-matured DCs to generate a specific CD4 T-cell
      response. This inhibitory effect was related to rapid and selective apoptosis of
      mature DCs. Anti-CD40-mediated apoptosis was due to an indirect mechanism
      involving cooperation with the death domain-associated receptor Fas, leading to
      activation of Fas-associated death domain protein (FADD) and caspase-8. On human
      cells, CD40 activation by such agonists could, therefore, trigger immune
      responses to antigens presented by immature DCs, which are otherwise
      nonimmunogenic, by inducing maturation. On the other hand, anti-CD40 mAbs, by
      rapidly inducing apoptosis, may reduce the capacity of inflammatory signal
      matured immunogenic DCs to generate an effective T-cell response. These results
      call for caution in CD40 mAb-based immunotherapy strategies.

PMID- 15994292
TI  - Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase
      activity of tumor suppressor PTEN.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a multifunctional
      tumor suppressor, has been shown to play a regulatory role in cell migration.
      Dictyostelium discoideum cells lacking PTEN exhibited impaired migration toward
      chemoattractant gradients. In the present study, we investigated the involvement
      of PTEN in chemotaxis of mammalian cells by examining PTEN-null Jurkat T cells.
      We observed that, in contrast to observations made in D discoideum, PTEN-null
      Jurkat T cells exhibited potent chemotactic responses to the chemokine stromal
      cell-derived factor 1alpha (SDF-1alpha), indicating that PTEN was not requisite
      for CXC chemokine receptor 4 (CXCR4)-mediated chemotaxis of Jurkat cells.
      Conversely, reconstitution of PTEN in Jurkat cells by using a tetracycline (Tet
      on)-inducible expression system down-regulated CXCR4-mediated chemotaxis.
      Furthermore, we established the lipid phosphatase activity of PTEN as essential
      for its inhibitory effect on chemotaxis. In addition, using PTEN-expressing T
      cell lines and primary T cells, we demonstrated that down-regulation of PTEN
      expression with vector-based small interfering RNAs (siRNAs) enhanced CXCR4
      mediated chemotaxis. Based on these results, we conclude that PTEN expression
      negatively regulates chemotaxis of lymphoid mammalian cells via its lipid
      phosphatase activity. Our findings may account for the reported increase in
      metastatic activity of PTEN-null tumor cells.

PMID- 15994293
TI  - A vision for the future: notes from the NHLBI director.

PMID- 15994294
TI  - Transcription-dependent association of multiple positive transcription elongation
      factor units to a HEXIM multimer.
AB  - The positive transcription elongation factor (P-TEFb) comprises a kinase, CDK9,
      and a Cyclin T1 or T2. Its activity is inhibited by association with the HEXIM1
      or HEXIM2 protein bound to 7SK small nuclear RNA. HEXIM1 and HEXIM2 were found to
      form stable homo- and hetero-oligomers. Using yeast two-hybrid and transfection
      assays, we have now shown that the C-terminal domains of HEXIM proteins directly
      interact with each other. Hydrodynamic parameters measured by glycerol gradient
      ultracentrifugation and gel-permeation chromatography demonstrate that both
      purified recombinant and cellular HEXIM1 proteins form highly anisotropic
      particles. Chemical cross-links suggest that HEXIM1 proteins form dimers. The
      multimeric nature of HEXIM1 is maintained in P-TEFb.HEXIM1.7SK RNA complexes.
      Multiple P-TEFb modules are found in the inactive P-TEFb.HEXIM1.7SK complexes. It
      is proposed that 7SK RNA binding to a HEXIM1 multimer promotes the simultaneous
      recruitment and hence inactivation of multiple P-TEFb units.

PMID- 15994295
TI  - Renal carcinoma-associated transcription factors TFE3 and TFEB are leukemia
      inhibitory factor-responsive transcription activators of E-cadherin.
AB  - Translocations of the genes encoding the related transcription factors TFE3 and
      TFEB are almost exclusively associated with a rare juvenile subset of renal cell
      carcinoma and lead to overexpression of TFE3 or TFEB protein sequences. A better
      understanding of how deregulated TFE3 and TFEB contribute to the transformation
      process requires elucidating more of the normal cellular processes in which they
      participate. Here we identify TFE3 and TFEB as cell type-specific leukemia
      inhibitory factor-responsive activators of E-cadherin. Overexpression of TFE3 or
      TFEB in 3T3 cells activated endogenous and reporter E-cadherin expression.
      Conversely, endogenous TFE3 and/or TFEB was required for endogenous E-cadherin
      expression in primary mouse embryonic fibroblasts and human embryonic kidney
      cells. Chromatin precipitation analyses and E-cadherin promoter reporter gene
      assays revealed that E-cadherin induction by TFE3 or TFEB was primarily or
      exclusively direct and mitogen-activated protein kinase-dependent in those cell
      types. In mouse embryonic fibroblasts, TFE3 and TFEB activation of E-cadherin was
      responsive to leukemia inhibitory factor. In 3T3 cells, TFE3 and TFEB expression
      also induced expression of Wilms' tumor-1, another E-cadherin activator. In
      contrast, E-cadherin expression in model mouse and canine renal epithelial cell
      lines was indifferent to inhibition of endogenous TFE3 and/or TFEB and was
      reduced by TFE3 or TFEB overexpression. These results reveal new cell type
      specific activities of TFE3 and TFEB which may be affected by their mutation.

PMID- 15994296
TI  - Mechanism of redox-mediated guanine nucleotide exchange on redox-active Rho
      GTPases.
AB  - Rho GTPases regulate multiple cellular processes including actin cytoskeletal
      rearrangements, transcriptional regulation, and oxidant production. The studies
      described herein demonstrate that small molecule redox agents, in addition to
      protein regulatory factors, can regulate the activity of redox-active Rho
      GTPases. A novel (GXXXXGK(S/T)C) motif, conserved in a number of Rho GTPases,
      appears critical for redox-mediated guanine nucleotide dissociation in vitro. A
      detailed molecular mechanism for redox regulation of GXXXXGK(S/T)C motif
      containing Rho GTPases is proposed.

PMID- 15994297
TI  - Role of the executioner caspases during lens development.
AB  - The notion that the cell death machinery is utilized during lens organelle
      degradation is supported by the observation that well characterized apoptotic
      substrates are cleaved during this process. Here, we test directly the role of
      executioner caspases (caspase-3, -6, and -7) in fiber cell differentiation. The
      distribution of mRNA, protein, and enzymatic activity for each caspase was
      determined in the mouse lens. Transcripts for all three executioner caspases were
      identified in lens fiber cells by real time RT-PCR, although only caspase-6 and 
      7 proteins were detected subsequently by Western blot analysis. Endogenous
      proteolytic activity was noted for caspase-3 but not caspase-6 or -7. We tested
      the role of executioner caspases in organelle degradation by examining lenses
      from mice deficient in each caspase. Knock-out lenses appeared grossly normal
      with the exception of caspase-3(-/-) lenses, which exhibited marked cataracts at
      the anterior lens pole. The distribution of lens organelles was mapped by
      confocal microscopy. There was no significant difference in the size of the lens
      organelle-free zone (OFZ)1 between wild-type and knock-out lenses. In response to
      treatment with staurosporine, caspase-3 and -6 (but not caspase-7) enzymatic
      activities were induced. We generated double knock-out animals to examine the
      phenotype of lenses deficient in both caspase-3 and -6. Histological examination
      of such lenses indicated the presence of a properly formed OFZ. Thus, no single
      executioner caspase (nor a combination of caspase-3 and -6) is required for
      organelle loss, although caspase-3 activity may be required for other aspects of
      lens transparency.

PMID- 15994298
TI  - Identification of a crucial histidine involved in metal transport activity in the
      Arabidopsis cation/H+ exchanger CAX1.
AB  - In plants, yeast, and bacteria, cation/H+ exchangers (CAXs) have been shown to
      translocate Ca2+ and other metal ions utilizing the H+ gradient. The best
      characterized of these related transporters is the plant vacuolar localized CAX1.
      We have used site-directed mutagenesis to assess the impact of altering the seven
      histidine residues to alanine within Arabidopsis CAX1. The mutants were expressed
      in a Saccharomyces cerevisiae strain that is sensitive to Ca2+ and other metals.
      By utilizing a yeast growth assay, the H338A mutant was the only mutation that
      appeared to alter Ca2+ transport activity. The CAX1 His338 residue is conserved
      among various CAX transporters and may be located within a filter for cation
      selection. We proceeded to mutate His338 to every other amino acid residue and
      utilized yeast growth assays to estimate the transport properties of the 19 CAX
      mutants. Expression of 16 of these His338 mutants could not rescue any of the
      metal sensitivities. However, expression of H338N, H338Q, and H338K allowed for
      some growth on media containing Ca2+. Most interestingly, H338N exhibited
      increased tolerance to Cd2+ and Zn2+. Endomembrane fractions from yeast cells
      were used to measure directly the transport of H338N. Although the H338N mutant
      demonstrated 25% of the wild type Ca2+/H+ transport, it showed an increase in
      transport for both Cd2+ and Zn2+ reflected in a decrease in the Km for these
      substrates. This study provides insights into the CAX cation filter and novel
      mechanisms by which metals may be partitioned across membranes.

PMID- 15994299
TI  - Point mutations in the proline-rich region of p22phox are dominant inhibitors of
      Nox1- and Nox2-dependent reactive oxygen generation.
AB  - The integral membrane protein p22phox is an indispensable component of the
      superoxide-generating phagocyte NADPH oxidase, whose catalytic core is the
      membrane-associated gp91phox (also known as Nox2). p22phox associates with
      gp91phox and, through its proline-rich C terminus, provides a binding site for
      the tandem Src homology 3 domains of the activating subunit p47phox. Whereas
      p22phox is expressed ubiquitously, its participation in regulating the activity
      of other Nox enzymes is less clear. This study investigates the requirement of
      p22phox for Nox enzyme activity and explores the role of its proline-rich region
      (PRR) for regulating activity. Coexpression of specific Nox catalytic subunits
      (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory
      subunits (NOXO1/NOXA1 for Nox1; p47phox/p67phox/Rac for Nox2; NOXO1 for Nox3; no
      subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen.
      Small interfering RNAs decreased endogenous p22phox expression and inhibited
      reactive oxygen generation from Nox1, Nox2, Nox3, and Nox4 but not Nox5.
      Truncated forms of p22phox that disrupted the PRR-inhibited reactive oxygen
      generation from Nox1, Nox2, and Nox3 but not from Nox4 and Nox5. Similarly,
      p22phox (P156Q), a mutation that disrupts Src homology 3 binding by the PRR,
      potently inhibited reactive oxygen production from Nox1 and Nox2 but not from
      Nox4 and Nox5. Expression of p22phox (P156Q) inhibited NOXO1-stimulated Nox3
      activity, but co-expression of NOXA1 overcame the inhibitory effect. The P157Q
      and P160Q mutations of p22phox showed selective inhibition of
      Nox2/p47phox/p67phox, and selectivity was specific for the organizing subunit
      (p47phox or NOXO1) rather than the Nox catalytic subunit. These studies stress
      the importance of p22phox for the function of Nox1, Nox2, Nox3, and Nox4, and
      emphasize the key role of the PRR for regulating Nox proteins whose activity is
      dependent upon p47phox or NOXO1.

PMID- 15994300
TI  - Two different zinc transport complexes of cation diffusion facilitator proteins
      localized in the secretory pathway operate to activate alkaline phosphatases in
      vertebrate cells.
AB  - Zinc is an essential component for the catalytic activity of numerous zinc
      requiring enzymes. However, until recently little has been known about the
      molecules involved in the pathways required for supplying zinc to these enzymes.
      We showed recently (Suzuki, T., Ishihara, K., Migaki, H., Matsuura, W., Kohda,
      A., Okumura, K., Nagao, M., Yamaguchi-Iwai, Y., and Kambe, T. (2005) J. Biol.
      Chem. 280, 637-643) that zinc transporters, ZnT5 and ZnT7, are required for the
      activation of zinc-requiring enzymes, alkaline phosphatases (ALPs), by
      transporting zinc into the lumens of the Golgi apparatus and the vesicular
      compartments where ALPs locate and converting apoALPs to holoALPs. ZnT6 is also
      located in the vesicular compartments like ZnT5 and ZnT7. However, the functions
      of ZnT6 and relationships among these three transporters have not been
      characterized yet. Here, we characterized the cellular function of ZnT6 together
      with ZnT5 and ZnT7 by gene-targeting studies using DT40 cells. ZnT6-deficient
      DT40 cells showed low ALP activity, suggesting that ZnT6 is required for the
      activation of zinc-requiring enzymes like ZnT5 and ZnT7. Combined disruptions of
      three transporter genes and re-expressions of transgenes revealed that ZnT5 and
      ZnT6 work in the same pathway, whereas ZnT7 acts alone. Furthermore, co
      immunoprecipitation studies revealed that ZnT5 and ZnT6 formed hetero-oligomers,
      whereas ZnT7 formed homo-oligomers. Interestingly, the Ser-rich loop in ZnT6, a
      potential zinc-binding site, was dispensable for the zinc-supplying function of
      ZnT5/ZnT6 hetero-oligomers, suggesting that the His-rich loop in ZnT5 may be
      important for zinc binding and that the loop in ZnT6 may acquire another function
      in the hetero-oligomer formation. These results suggest that two different zinc
      transport complexes operate to activate ALPs.

PMID- 15994301
TI  - Caspartin and calprismin, two proteins of the shell calcitic prisms of the
      Mediterranean fan mussel Pinna nobilis.
AB  - We used the combination of preparative electrophoresis and immunological
      detection to isolate two new proteins from the shell calcitic prisms of Pinna
      nobilis, the Mediterranean fan mussel. The amino acid composition of these
      proteins was determined. Both proteins are soluble, intracrystalline, and acidic.
      The 38-kDa protein is glycosylated; the 17-kDa one is not. Ala, Asx, Thr, and Pro
      represent the dominant residues of the 38-kDa protein, named calprismin. An N
      terminal sequence was obtained from calprismin. This sequence, which comprises a
      pattern of 4 cysteine residues, is not related to any known protein. The second
      protein, named caspartin, exhibits an unusual amino acid composition, since Asx
      constitutes by far the main amino acid residue. Preliminary sequencing
      surprisingly suggests that the first 75 N-terminal residues are all Asp.
      Caspartin self-aggregates spontaneously into multimers. In vitro tests show that
      it inhibits the precipitation of calcium carbonate. Furthermore, it strongly
      interferes with the growth of calcite crystals. A polyclonal antiserum raised
      against caspartin was used to localize this protein in the shell by immunogold.
      The immunolocalization demonstrates that caspartin is distributed within the
      prisms and makes a continuous film at the interface between the prisms and the
      surrounding insoluble sheets. Our finding emphasizes the prominent role of
      aspartic acid-rich proteins for the building of calcitic prisms among molluscs.

PMID- 15994302
TI  - Highly conserved O-fucose sites have distinct effects on Notch1 function.
AB  - The extracellular domain of mouse Notch1 contains 36 tandem epidermal growth
      factor-like (EGF) repeats, many of which are modified with O-fucose. Previous
      work from several laboratories has indicated that O-fucosylation plays an
      important role in ligand mediated Notch activation. Nonetheless, it is not clear
      whether all, or a subset, of the EGF repeats need to be O-fucosylated. Three O
      fucose sites are invariantly conserved in all Notch homologues with 36 EGF
      repeats (within EGF repeats 12, 26, and 27). To investigate which O-fucose sites
      on Notch1 are important for ligand-mediated signaling, we mutated the three
      invariant O-fucose sites in mouse Notch1, along with several less highly
      conserved sites, and evaluated their ability to transduce Jagged1- and Delta1
      mediated signaling in a cell-based assay. Our analysis revealed that mutation of
      any of the three invariant O-fucose sites resulted in significant changes in both
      Delta1 and Jagged1 mediated signaling, but mutations in less highly conserved
      sites had no detectable effect. Interestingly, mutation of each invariant site
      gave a distinct effect on Notch function. Mutation of the O-fucose site in EGF
      repeat 12 resulted in loss of Delta1 and Jagged1 signaling, while mutation of the
      O-fucose site in EGF repeat 26 resulted in hyperactivation of both Delta1 and
      Jagged1 signaling. Mutation of the O-fucose site in EGF repeat 27 resulted in
      faulty trafficking of the Notch receptor to the cell surface and a decreased S1
      processing of the receptor. These results indicate that the most highly conserved
      O-fucose sites in Notch1 are important for both processing and ligand-mediated
      signaling in the context of a cell-based signaling assay.

PMID- 15994303
TI  - Atypical protein kinase Ciota plays a critical role in human lung cancer cell
      growth and tumorigenicity.
AB  - Atypical protein kinase C (aPKC) isozymes function in epithelial cell polarity,
      proliferation, and survival and have been implicated in cellular transformation.
      However, the role of these enzymes in human cancer is largely unexplored. Here,
      we report that aPKCiota is highly expressed in human non-small cell lung cancer
      cell lines, whereas the closely related aPKC isozyme PKCzeta is undetectable in
      these cells. Disruption of PKCiota signaling reveals that PKCiota is dispensable
      for adherent growth of non-small cell lung cancer cells but is required for
      transformed growth in soft agar in vitro and for tumorigenicity in vivo.
      Molecular dissection of signaling down-stream of PKCiota demonstrates that Rac1
      is a critical molecular target for PKCiota-dependent transformation, whereas
      PKCiota is not necessary for NFkappaB activation in vitro or in vivo. Expression
      of the PB1 domain of PKCiota (PKCiota-(1-113)) blocks PKCiota-dependent Rac1
      activity and inhibits cellular transformation indicating a role for this domain
      in the transforming activity of PKCiota. Taken together, our data demonstrate
      that PKCiota is a critical lung cancer gene that activates a Rac1-->Pak-->Mek1,2-
      >Erk1,2 signaling pathway required for transformed growth. Our data indicate that
      PKCiota may be an attractive molecular target for mechanism-based therapies for
      treatment of lung cancer.

PMID- 15994304
TI  - X-ray snapshots of peptide processing in mutants of tricorn-interacting factor F1
      from Thermoplasma acidophilum.
AB  - The tricorn-interacting factor F1 of the archaeon Thermoplasma acidophilum
      cleaves small hydrophobic peptide products of the proteasome and tricorn
      protease. F1 mutants of the active site residues that are involved in substrate
      recognition and catalysis displayed distinct activity patterns toward fluorogenic
      test substrates. Crystal structures of the mutant proteins complexed with
      peptides Phe-Leu, Pro-Pro, or Pro-Leu-Gly-Gly showed interaction of glutamates
      213 and 245 with the N termini of the peptides and defined the S1 and S1' sites
      and the role of the catalytic residues. Evidence was found for processive peptide
      cleavage in the N-to-C direction, whereby the P1' product is translocated into
      the S1 site. A functional interaction of F1 with the tricorn protease was
      observed with the inactive F1 mutant G37A. Moreover, small angle x-ray scattering
      measurements for tricorn and inhibited F1 have been interpreted as formation of
      transient and substrate-induced complexes.

PMID- 15994305
TI  - Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with
      p35, p25, or p39.
AB  - One of the major pathological hallmarks of Alzheimer disease is neurofibrillary
      tangles. Neurofibrillary tangles are bundles of paired helical filaments composed
      of hyperphosphorylated tau. Cyclin-dependent kinase 5 (Cdk5) is one of the tau
      protein kinases that increase paired helical filament epitopes in tau by
      phosphorylation. Recently, various mutations of tau have been identified in
      frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Here,
      we investigated the phosphorylation of FTDP-17 mutant tau proteins, K257T, P301L,
      P301S, and R406W, by Cdk5 complexed with p35, p25, or p39 in vitro and in
      cultured cells. The extent of phosphorylation by all Cdk5 species was slightly
      lower in mutant tau than in wild-type tau. Major phosphorylation sites, including
      Ser202, Ser235, and Ser404, were the same among the wild-type, K257T, P301L, and
      P301S tau proteins phosphorylated by any Cdk5. On the other hand, R406W tau was
      less phosphorylated at Ser404 than were the other variants. This was not due to
      the simple replacement of amino acid Arg406 with Trp close to the phosphorylation
      site, because Ser404 in a R406W peptide was equally phosphorylated in a wild-type
      peptide. The decreased phosphorylation of mutant tau by Cdk5s was canceled when
      tau protein bound to microtubules was phosphorylated. These results indicate that
      FTDP-17 mutations do not affect the phosphorylatability of tau by Cdk5 complexed
      with p35, p25, or p39 and may explain part of the discrepancy reported previously
      between in vivo and in vitro phosphorylation of FTDP-17 tau mutants.

PMID- 15994306
TI  - Arrest-defective-1 protein, an acetyltransferase, does not alter stability of
      hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF.
AB  - The hypoxia-inducible factor (HIF) is a key player in a transcriptional pathway
      that controls the hypoxic response of mammalian cells. Post-translational
      modification of the alpha subunit of HIF determines its half-life and activity.
      Among the multiple reported modifications, acetylation, by an acetyltransferase
      termed arrest-defective-1 protein (ARD1), has been reported to decrease HIF
      1alpha stability and therefore impact on hypoxic gene expression. In contrast, we
      report that both overexpression and silencing of ARD1 had no impact on the
      stability of HIF-1alpha or -2alpha and that cells silenced for ARD1 maintained
      hypoxic nuclear localization of HIF-1alpha. In addition, we show that the ARD1
      mRNA and protein levels are not regulated by hypoxia in several human tumor cell
      lines, including cervical adenocarcinoma HeLa cells, fibrosarcoma HT1080 cells,
      adenovirus-transformed human kidney HEK293 cells, and human breast cancer MCF-7
      cells. Using two model systems ((a) wild-type and HIF-1alpha-null mouse embryo
      fibroblasts and (b) HeLa cells silenced for HIF-1alpha or -2alpha by RNA
      interference), we demonstrate that the level of expression of the ARD1 protein is
      independent of HIF-1alpha and -2alpha. We also demonstrate that ARD1 is a stable,
      predominantly cytoplasmic protein expressed in a broad range of tissues, tumor
      cell lines, and endothelial cells. Taken together, our findings demonstrate that
      ARD1 has limited, if any, impact on the HIF signaling pathway.

PMID- 15994307
TI  - Identification and characterization of a cyclic di-GMP-specific phosphodiesterase
      and its allosteric control by GTP.
AB  - Cyclic diguanylic acid (c-di-GMP) is a global second messenger controlling
      motility and adhesion in bacterial cells. Synthesis and degradation of c-di-GMP
      is catalyzed by diguanylate cyclases (DGC) and c-di-GMP-specific
      phosphodiesterases (PDE), respectively. Whereas the DGC activity has recently
      been assigned to the widespread GGDEF domain, the enzymatic activity responsible
      for c-di-GMP cleavage has been associated with proteins containing an EAL domain.
      Here we show biochemically that CC3396, a GGDEF-EAL composite protein from
      Caulobacter crescentus is a soluble PDE. The PDE activity, which rapidly converts
      c-di-GMP into the linear dinucleotide pGpG, is confined to the C-terminal EAL
      domain of CC3396, depends on the presence of Mg2+ ions, and is strongly inhibited
      by Ca2+ ions. Remarkably, the associated GGDEF domain, which contains an altered
      active site motif (GEDEF), lacks detectable DGC activity. Instead, this domain is
      able to bind GTP and in response activates the PDE activity in the neighboring
      EAL domain. PDE activation is specific for GTP (K(D) 4 microM) and operates by
      lowering the K(m) for c-di-GMP of the EAL domain to a physiologically significant
      level (420 nM). Mutational analysis suggested that the substrate-binding site (A
      site) of the GGDEF domain is involved in the GTP-dependent regulatory function,
      arguing that a catalytically inactive GGDEF domain has retained the ability to
      bind GTP and in response can activate the neighboring EAL domain. Based on this
      we propose that the c-di-GMP-specific PDE activity is confined to the EAL domain,
      that GGDEF domains can either catalyze the formation of c-di-GMP or can serve as
      regulatory domains, and that c-di-GMP-specific phosphodiesterase activity is
      coupled to the cellular GTP level in bacteria.

PMID- 15994308
TI  - Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide
      phosphodiesterases 4 and 7.
AB  - Phosphodiesterase (PDE) inhibitors have been widely studied as therapeutics for
      treatment of human diseases. However, the mechanism by which each PDE family
      recognizes selectively a category of inhibitors remains a puzzle. Here we report
      the crystal structure of PDE7A1 catalytic domain in complex with non-selective
      inhibitor 3-isobutyl-1-methylxanthine and kinetic analysis on the mutants of
      PDE7A1 and PDE4D2. Our studies suggest at least three elements play critical
      roles in inhibitor selectivity: 1) the conformation and position of an invariant
      glutamine, 2) the natures of scaffolding residues, and 3) residues that alter
      shape and size of the binding pocket. Kinetic analysis shows that single PDE7 to
      PDE4 mutations increase the sensitivity of PDE7 to PDE4 inhibitors but are not
      sufficient to render the engineered enzymes comparable with the wild types. The
      triple S373Y/S377T/I412S mutation of PDE7A1 produces a PDE4-like enzyme, implying
      that multiple elements must work together to determine inhibitor selectivity.

PMID- 15994309
TI  - Depletion of anaphase-promoting complex or cyclosome (APC/C) subunit homolog APC1
      or CDC27 of Trypanosoma brucei arrests the procyclic form in metaphase but the
      bloodstream form in anaphase.
AB  - The anaphase-promoting complex or cyclosome (APC/C) is a multiprotein subunit E3
      ubiquitin ligase complex that controls segregation of chromosomes and exit from
      mitosis in eukaryotes. It triggers elimination of key cell cycle regulators such
      as securin and mitotic cyclins during mitosis by polyubiquitinating them for
      proteasome degradation. Seven core subunit homologs of APC/C (APC1, APC2, APC11,
      CDC16, CDC23, CDC27, and DOC1) were identified in the Trypanosoma brucei genome
      data base. Expression of six of them was individually ablated by RNA interference
      in both the procyclic and bloodstream forms of T. brucei. Only the CDC27- and
      APC1-depleted cells were enriched in the G2/M phase with inhibited growth.
      Further studies indicated that T. brucei APC1 and CDC27 failed to complement the
      corresponding deletion mutants of budding yeast. However, their depletion from
      procyclic-form T. brucei enriched cells with two kinetoplasts and an enlarged
      nucleus possessing short metaphase-like mitotic spindles, suggesting that APC1
      and CDC27 may play essential roles in promoting anaphase in the procyclic form.
      Their depletion from the bloodstream form, however, enriched cells with two
      kinetoplasts and two nuclei connected through a microtubule bundle, suggesting a
      late anaphase arrest. This is the first time functional APC/C subunit homologs
      were identified in T. brucei. The apparent differential activities of this
      putative APC/C in two distinct developmental stages suggest an unusual function.
      The apparent lack of functional involvement of some of the other individual
      structural subunit homologs of APC/C may indicate the structural uniqueness of T.
      brucei APC/C.

PMID- 15994310
TI  - Cysteine-scanning mutagenesis of serotonin transporter intracellular loop 2
      suggests an alpha-helical conformation.
AB  - Like other proteins involved in neurotransmitter transport, serotonin transporter
      (SERT) activity is regulated by multiple intracellular signal transduction
      pathways. The second intracellular loop (IL2) of SERT contains consensus
      sequences for cGMP-dependent protein kinase and protein kinase C. A 24-residue
      region of SERT including IL2, from Ile-270 through Ser-293, was analyzed by
      cysteine-scanning mutagenesis and chemical modification. 2
      (Aminoethyl)methanethiosulfonate hydrobromide (MTSEA) failed to inhibit serotonin
      transport or binding of the cocaine analog 2beta-carbomethoxy-3beta-(4
      [125I]iodophenyl)tropane (beta-CIT) in intact cells expressing these mutants, but
      it inactivated beta-CIT binding in membrane preparations. From the pattern of
      sensitivity, IL2 appears to extend from Trp-271 through Ile-290, a significantly
      longer region than that initially predicted by hydropathy analysis. Six mutants
      reacted with MTSEA much faster than the others, and the pattern of the more
      reactive mutations suggested that IL2 is in an alpha-helical conformation. Some
      of the mutants had significantly elevated transport rates, suggesting a possible
      mechanism for the regulation of SERT activity.

PMID- 15994311
TI  - Decorin evokes protracted internalization and degradation of the epidermal growth
      factor receptor via caveolar endocytosis.
AB  - Decorin inhibits the epidermal growth factor receptor (EGFR) by down-regulating
      its tyrosine kinase activity, thereby blocking the growth of a variety of
      transformed cells and tumor xenografts. In this study we provide evidence that
      decorin directly binds to the EGFR causing its dimerization, internalization, and
      ultimately its degradation. Using various pharmacological agents to disrupt
      clathrin-dependent and -independent endocytosis, we demonstrate that decorin
      evokes a protracted internalization of the EGFR primarily via caveolar-mediated
      endocytosis. In contrast to EGF, decorin targets the EGFR to caveolae, but not to
      early or recycling endosomes. Ultimately, however, both EGF- and decorin-induced
      pathways converge into late endosomes/lysosomes for final degradation. Thus, we
      have discovered a novel biological mechanism for decorin that could explain its
      anti-proliferative and anti-oncogenic mode of action.

PMID- 15994312
TI  - Focal adhesion kinase plays a pivotal role in herpes simplex virus entry.
AB  - Development of strategies to prevent herpes simplex virus (HSV) infection
      requires knowledge of cellular pathways harnessed by the virus for invasion. This
      study demonstrates that HSV induces rapid phosphorylation of focal adhesion
      kinase (FAK) in several human target cells and that phosphorylation is important
      for entry post-binding. Nuclear transport of the viral tegument protein VP16,
      transport of viral capsids to the nuclear pore, and downstream events (including
      expression of immediate-early genes and viral plaque formation) were
      substantially reduced in cells transfected with dominant-negative mutants of FAK
      or small interfering RNA designed to inhibit FAK expression. These observations
      were substantiated using mouse embryonic fibroblast cells derived from embryonic
      FAK-deficient mice. Infection was reduced by >90% in knockout cells relative to
      control cells and was further reduced if the knockout cells were transfected with
      small interfering RNA targeting proline-rich tyrosine kinase-2, which was also
      phosphorylated in response to HSV. The knockout cells were permissive for viral
      binding, and virus triggered an intracellular calcium response, but nuclear
      transport was inhibited. Together, these results support a novel model for
      invasion that implicates FAK phosphorylation as important for delivery of viral
      capsids to the nuclear pore.

PMID- 15994313
TI  - Histone deacetylase inhibitors suppress the induction of c-Jun and its target
      genes including COX-2.
AB  - Cyclooxygenase-2 (COX-2) is considered to be a target for anticancer therapy.
      Histone deacetylase (HDAC) inhibitors exhibit antitumor activity, but the
      mechanisms of action are incompletely understood. We investigated whether HDAC
      inhibitors blocked AP-1-mediated activation of COX-2 transcription. Trichostatin
      A and suberoylanilide hydroxamic acid, two structurally related inhibitors of
      HDAC activity, blocked AP-1-mediated induction of COX-2 expression and
      prostaglandin E2 biosynthesis. Chromatin immunoprecipitation assays indicated
      that HDAC inhibitors suppressed c-Jun binding to the COX-2 promoter and thereby
      blocked transcription. The observed reduction in binding reflected reduced levels
      of c-Jun. HDAC inhibitors suppressed the induction of c-jun transcription by
      blocking the recruitment of the preinitiation complex (RNA polymerase II and
      TFIIB) to the c-jun promoter. HDAC3 but not HDAC1 or HDAC2 was required for AP-1
      mediated stimulation of c-jun expression. Because HDAC inhibitors suppressed the
      induction of c-jun gene expression, resulting in reduced COX-2 transcription, it
      was important to determine whether other known AP-1 target genes were also
      modulated. Cyclin D1 and collagenase-1 are AP-1-dependent genes that have been
      implicated in carcinogenesis. HDAC inhibitors suppressed the induction of both
      cyclin D1 and collagenase-1 transcription by inhibiting the binding of c-Jun to
      the respective promoters. Taken together, these results suggest that HDAC
      inhibitors block the induction of c-jun transcription by inhibiting the
      recruitment of the preinitiation complex to the c-jun promoter. This led, in
      turn, to reduced expression of several activator protein-1-dependent genes (COX
      2, cyclin D1, collagenase-1). These findings provide new insights into the
      mechanisms underlying the antitumor activity of HDAC inhibitors.

PMID- 15994314
TI  - Both high mobility group (HMG)-boxes and the acidic tail of HMGB1 regulate
      recombination-activating gene (RAG)-mediated recombination signal synapsis and
      cleavage in vitro.
AB  - RAG-1 and RAG-2 initiate V(D)J recombination through synapsis and cleavage of a
      12/23 pair of V(D)J recombination signal sequences (RSS). RAG-RSS complex
      assembly and activity in vitro is promoted by high mobility group proteins of the
      "HMG-box" family, exemplified by HMGB1. How HMGB1 stimulates the DNA binding and
      cleavage activity of the RAG complex remains unclear. HMGB1 contains two
      homologous HMG-box DNA binding domains, termed A and B, linked by a stretch of
      basic residues to a highly acidic C-terminal tail. To identify determinants of
      HMGB1 required for stimulation of RAG-mediated RSS binding and cleavage, we
      prepared an extensive panel of mutant HMGB1 proteins and tested their ability to
      augment RAG-mediated RSS binding and cleavage activity. Using a combination of
      mobility shift and in-gel cleavage assays, we find that HMGB1 promotes RAG
      mediated cleavage largely through the activity of box B, but optimal stimulation
      requires a functional A box tethered in the correct orientation. Box A or B
      mutants fail to promote RAG synaptic complex formation, but this defect is
      alleviated when the acidic tail is removed from these mutants.

PMID- 15994315
TI  - Protein phosphatase 2A regulates apoptosis in intestinal epithelial cells.
AB  - Polyamine depletion prevents apoptosis by increasing serine/threonine
      phosphorylation leading to either inactivation or activation of pro- and anti
      apoptotic proteins, respectively. Despite evidence that protein kinases are
      regulators of apoptosis, a specific role for protein phosphatases in regulating
      cell survival has not been established. In this study, we show that polyamine
      depletion inhibits serine/threonine phosphatase 2A (PP2A). Inhibition of PP2A in
      cells depleted of polyamines correlated well with increased phosphorylation of
      Bad at Ser112. Bad Ser112 phosphorylation in response to tumor necrosis factor
      (TNF)-alpha treatment decreased with time in cells grown in control as well as
      those grown in the presence of alpha-difluoromethylornithine plus putrescine.
      However, a sustained increase in the levels of Bad Ser112 phosphorylation was
      maintained in response to TNF-alpha treatment in cells grown in the presence of
      alpha-difluoromethylornithine. Inhibition of PP2A by okadaic acid and fostriecin
      or PP2A small interfering RNA transfection significantly decreased TNF-alpha
      induced apoptosis in control and polyamine-depleted cells. Inhibition of PP2A by
      okadaic acid: 1) increased Bad and Bcl-2 phosphorylation at Ser112 and Ser70,
      respectively; 2) increased ERK activity; 3) prevented JNK activation; 4)
      prevented cytochrome c release, and activation of caspases-9 and -3 in response
      to TNF-alpha. Inhibition of MEK1 by U0126 prevented phosphorylation of Bad at
      Ser112. These results indicate that polyamines regulate PP2A activity, and
      inhibition of PP2A in response to polyamine depletion increases steady state
      levels of Bad and Bcl-2 proteins and their phosphorylation and thereby prevents
      cytochrome c release, caspase-9, and caspase-3 activation.

PMID- 15994316
TI  - Functionally independent AU-rich sequence motifs regulate KC (CXCL1) mRNA.
AB  - Certain pro-inflammatory chemokine mRNAs containing adenine/uridine-rich sequence
      elements (AREs) in their 3' untranslated regions (3'-UTRs) are known to exhibit
      constitutive instability and sensitivity to proinflammatory stimuli resulting in
      the stabilization of the message. Using tetR-regulated transcription we now show
      that the 3'-UTR of the mouse CXCL1 (KC) mRNA contains at least two ARE motifs
      that are structurally and functionally distinct. A fragment of 77 nucleotides
      containing 4 clustered AUUUA pentamers located at the 5'-end of the KC 3'-UTR is
      only modestly unstable yet promotes markedly enhanced, post-transcriptional
      protein production in response to either interleukin-1alpha (IL-1alpha) or
      lipopolysaccharide (LPS), suggesting translational regulation. In contrast, a
      fragment containing 3 isolated AUUUA pentamers corresponding to the residual 3'
      400 nucleotides of the KC 3'-UTR confers both instability and is stabilized in
      response to IL-1alpha. Although the clustered AUUUA pentamers in the upstream
      region are required for stimulus sensitivity, mutation of all three pentamers in
      the downstream region has little or no effect on either instability or stimulus
      sensitivity. The upstream region is comparably stabilized in response to either
      IL-1alpha or LPS, whereas the AUUUA-independent downstream determinant is
      differentially more sensitive to IL-1alpha. Finally, using UV-induced RNA cross
      linking, these functionally independent sequences exhibit different patterns of
      interaction with RNA-binding proteins. Collectively, these findings document the
      presence of multiple independent determinants of KC mRNA function and demonstrate
      that these operate via distinct mechanisms.

PMID- 15994317
TI  - The platelet-derived growth factor receptor-beta phosphorylates and activates G
      protein-coupled receptor kinase-2. A mechanism for feedback inhibition.
AB  - G protein-coupled receptor kinase-2 (GRK2) serine-phosphorylates the platelet
      derived growth factor receptor-beta (PDGFRbeta), and thereby diminishes signaling
      by the receptor. Because activation of GRK2 may involve phosphorylation of its N
      terminal tyrosines by c-Src, we tested whether the PDGFRbeta itself could
      tyrosine-phosphorylate and activate GRK2. To do so, we used wild type (WT) and
      Y857F mutant PDGFRbetas in HEK cells, which lack endogenous PDGFRs. The Y857F
      PDGFRbeta autophosphorylates normally but does not phosphorylate exogenous
      substrates. Although PDGF-stimulated Y857F and WT PDGFRbetas activated c-Src
      equivalently, the WT PDGFRbeta tyrosine-phosphorylated GKR2 60-fold more than the
      Y857F PDGFRbeta in intact cells. With purified GRK2 and either WT or Y857F
      PDGFRbetas immunoprecipitated from HEK cells, GRK2 tyrosyl phosphorylation was
      PDGF-dependent and required the WT PDGFRbeta, even though the WT and Y857F
      PDGFRbetas autophosphorylated equivalently. This PDGFRbeta-mediated GRK2 tyrosyl
      phosphorylation enhanced GRK2 activity: GRK2-mediated seryl phosphorylation of
      the PDGFRbeta was 9-fold greater for the WT than for the Y857F in response to
      PDGF, but equivalent when GRK2 was activated by sequential stimulation of beta2
      adrenergic and PDGF-beta receptors. Furthermore, both PDGFRbeta-mediated GRK2
      tyrosyl phosphorylation and GRK2-mediated PDGFRbeta seryl phosphorylation were
      reduced approximately 50% in intact cells by mutation to phenylalanine of three
      tyrosines in the N-terminal domain of GRK2. We conclude that the activated
      PDGFRbeta itself phosphorylates GRK2 tyrosyl residues and thereby activates GRK2,
      which then serine-phosphorylates and desensitizes the PDGFRbeta.

PMID- 15994318
TI  - Negative transcriptional modulation and silencing of the bi-exonic Rnf35 gene in
      the preimplantation embryo. Binding of the CCAAT-displacement protein/Cux to the
      untranslated exon 1 sequence.
AB  - Previous works have indicated promiscuous transcription from the zygotic genome
      immediately after fertilization. The mouse Rnf35 gene is bi-exonic in structure
      and is transcribed in the preimplantation embryo until it is permanently silenced
      at the blastocyst stage of development. We have previously shown that Rnf35
      transcription is positively regulated by the nuclear factor Y. Using the uniquely
      permissive Chinese hamster ovary-K1 cell line in transient transfection assays,
      we demonstrate in this work that the Rnf35 promoter was negatively modulated by a
      cis-cognate repressor element, designated as the downstream exon 1 repressor, or
      DER, residing between +72 and +95 in the untranslated exon 1 of the Rnf35 gene.
      Simultaneous mutagenesis of the two half-sections, DER1 and DER2, of the DER
      sequence was required for derepression suggesting participation of multiple
      proteins in the DER-dependent transcriptional repression. Electrophoretic
      mobility shift assays demonstrated that the 3'-half of DER (DER2) was targeted by
      the repressor CCAAT-displacement protein (CDP)/Cux. Chromatin immunoprecipitation
      experiments further demonstrated in vivo CDP-DER association in the blastocyst
      and the 8.5 day embryo. Furthermore, the DER-dependent repression was partially
      relieved in vivo in co-transfection with an antisense CDP construct.
      Transcription of the Cdp gene was shown to first occur between the eight-cell and
      the blastocyst stages, correlating and possibly explaining the onset of Rnf35
      silencing at the blastocyst stage. Taken together, our results suggest that the
      evolutionarily acquired exon 1 of Rnf35, and possibly exon 1 of other similarly
      structured bi-exonic early embryonic genes, contributes to transcriptional
      modulation and silencing in the developing mouse embryo.

PMID- 15994319
TI  - Angiotensin II inhibits bTREK-1 K+ channels in adrenocortical cells by separate
      Ca2+- and ATP hydrolysis-dependent mechanisms.
AB  - Bovine adrenocortical cells express bTREK-1 K+ channels that set the resting
      membrane potential (V(m)) and couple angiotensin II (AngII) and
      adrenocorticotropic hormone (ACTH) receptors to membrane depolarization and
      corticosteroid secretion. In this study, it was discovered that AngII inhibits
      bTREK-1 by separate Ca2+- and ATP hydrolysis-dependent signaling pathways. When
      whole cell patch clamp recordings were made with pipette solutions that support
      activation of both Ca2+- and ATP-dependent pathways, AngII was significantly more
      potent and effective at inhibiting bTREK-1 and depolarizing adrenal zona
      fasciculata cells, than when either pathway is activated separately. External ATP
      also inhibited bTREK-1 through these two pathways, but ACTH displayed no Ca2+
      dependent inhibition. AngII-mediated inhibition of bTREK-1 through the novel Ca2+
      dependent pathway was blocked by the AT1 receptor antagonist losartan, or by
      including guanosine-5'-O-(2-thiodiphosphate) in the pipette solution. The Ca2+
      dependent inhibition of bTREK-1 by AngII was blunted in the absence of external
      Ca2+ or by including the phospholipase C antagonist U73122, the inositol 1,4,5
      trisphosphate receptor antagonist 2-amino-ethoxydiphenyl borate, or a calmodulin
      inhibitory peptide in the pipette solution. The activity of unitary bTREK-1
      channels in inside-out patches from adrenal zona fasciculata cells was inhibited
      by application of Ca2+ (5 or 10 microM) to the cytoplasmic membrane surface. The
      Ca2+ ionophore ionomycin also inhibited bTREK-1 currents through channels
      expressed in CHO-K1 cells. These results demonstrate that AngII and selected
      paracrine factors that act through phospholipase C inhibit bTREK-1 in
      adrenocortical cells through simultaneous activation of separate Ca2+- and ATP
      hydrolysis-dependent signaling pathways, providing for efficient membrane
      depolarization. The novel Ca2+-dependent pathway is distinctive in its lack of
      ATP dependence, and is clearly different from the calmodulin kinase-dependent
      mechanism by which AngII modulates T-type Ca2+ channels in these cells.

PMID- 15994320
TI  - Evolutionary trace-based peptides identify a novel asymmetric interaction that
      mediates oligomerization in nuclear receptors.
AB  - Germ cell nuclear factor (GCNF) is an orphan nuclear receptor that plays
      important roles in development and reproduction, by repressing the expression of
      essential genes such as Oct4, GDF9, and BMP15, through binding to DR0 elements.
      Surprisingly, whereas recombinant GCNF binds to DR0 sequences as a homodimer,
      endogenous GCNF does not exist as a homodimer but rather as part of a large
      complex termed the transiently retinoid-induced factor (TRIF). Here, we use
      evolutionary trace (ET) analysis to design mutations and peptides that probe the
      molecular basis for the formation of this unusual complex. We find that GCNF
      homodimerization and TRIF complex formation are DNA-dependent, and ET suggests
      that dimerization involves key functional sites on both helix 3 and helix 11,
      which are located on opposing surfaces of the ligand binding domain. Targeted
      mutations in either helix of GCNF disrupt the formation of both the homodimer and
      the endogenous TRIF complex. Moreover, peptide mimetics of both of these ET
      determined sites inhibit dimerization and TRIF complex formation. This suggests
      that a novel helix 3-helix 11 heterotypic interaction mediates GCNF interaction
      and would facilitate oligomerization. Indeed, it was determined that the
      endogenous TRIF complex is composed of a GCNF oligomer. These findings shed light
      on an evolutionarily selected mechanism that reveals the unusual DNA-binding,
      dimerization, and oligomerization properties of GCNF.

PMID- 15994321
TI  - Differential effects of lipoprotein lipase on tumor necrosis factor-alpha and
      interferon-gamma-mediated gene expression in human endothelial cells.
AB  - Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich
      lipoproteins. In vascular diseases, such as atherosclerosis, inflammation plays
      an important role in the pathogenesis of the disease. We examined the role of LPL
      in modulating tumor necrosis factor-alpha (TNF-alpha)- and interferon-gamma (IFN
      gamma)-mediated inflammatory cytokine signal transduction pathways in human
      aortic endothelial cells (HAECs). LPL significantly suppressed TNF-alpha-induced
      gene expression, and this suppression was reversed by tetrahydrolipstatin and
      heparinase. In contrast, LPL synergistically enhanced IFN-gamma-induced gene
      expression in HAECs. To elucidate the molecular mechanisms of LPL action, we
      investigated the role of transcription factors nuclear factor kappa B (NF-kappaB)
      and signal transducer and activator of transcription factor 1 (Stat1). The anti
      inflammatory response of LPL in suppressing TNF-alpha-induced gene expression was
      a result of its inhibition of NF-kappaB activity by the abrogation of IkappaB
      alpha degradation and phosphorylation of the p65 subunit. Although LPL alone had
      no effect on Stat1 activation, LPL enhanced IFN-gamma-induced phosphorylation of
      Stat1 on tyrosine 701 and serine 727, as well as Stat1-mediated transactivation.
      The synergistic effect of LPL on IFN-gamma-induced Stat1 activation was mediated
      by enhanced activation of the tyrosine kinase JAK2 and was abrogated by LY294002,
      a specific inhibitor of the phosphatidylinositol 3'-kinase pathway. Our studies
      indicate that LPL has differential effects on several inflammatory pathways known
      to be important in atherosclerosis.

PMID- 15994322
TI  - Siderophore transport through Escherichia coli outer membrane receptor FhuA with
      disulfide-tethered cork and barrel domains.
AB  - The hydroxamate siderophore receptor FhuA is a TonB-dependent outer membrane
      protein of Escherichia coli composed of a C-terminal 22-stranded beta-barrel
      occluded by an N-terminal globular cork domain. During siderophore transport into
      the periplasm, the FhuA cork domain has been proposed to undergo conformational
      changes that allow transport through the barrel lumen; alternatively, the cork
      may be completely displaced from the barrel. To probe such changes, site-directed
      cysteine mutants in the cork domain (L109C and Q112C) and in the barrel domain
      (S356C and M383C) were created within the putative siderophore transport pathway.
      Molecular modeling predicted that the double cysteine mutants L109C/S356C and
      Q112C/M383C would form disulfide bonds, thereby tethering the cork and barrel
      domains. The double cysteine FhuA mutants were denatured under nonreducing
      conditions and fluorescently labeled with thiol-specific Oregon Green maleimide.
      Subsequent SDS-PAGE analysis revealed two distinct species: FhuA containing a
      disulfide bond and FhuA with free sulfhydryl groups. To address the role of the
      putative siderophore transport pathway and to evaluate possible rearrangements of
      the cork domain during ferricrocin transport, disulfide bond formation was
      enhanced by an oxidative catalyst. Cells containing double cysteine FhuA mutants
      that were subjected to oxidation during ferricrocin transport exhibited disulfide
      bond formation to near completion. After disulfide tethering of the cork to the
      barrel, ferricrocin transport was equivalent to transport by untreated cells.
      These results demonstrate that blocking the putative siderophore transport
      pathway does not abrogate ferricrocin uptake. We propose that, during siderophore
      transport through FhuA, the cork domain remains within the barrel rather than
      being displaced.

PMID- 15994323
TI  - Identification of conserved prolyl residue important for transport activity and
      the substrate specificity range of yeast plasma membrane Na+/H+ antiporters.
AB  - Yeast plasma membrane Na+/H+ antiporters are divided according to their substrate
      specificity in two distinct subfamilies. To identify amino acid residues
      responsible for substrate specificity determination (recognition of K+), the
      Zygosaccharomyces rouxii Sod2-22 antiporter (non-transporting K+) was mutagenized
      and a collection of ZrSod2-22 mutants that improved the KCl tolerance of a salt
      sensitive Saccharomyces cerevisiae strain was isolated. Several independent
      ZrSod2-22 mutated alleles contained the replacement of a highly conserved proline
      145 with a residue containing a hydroxyl group (Ser, Thr). Site-directed
      mutagenesis of Pro145 proved that an amino acid with a hydroxyl group at this
      position is enough to enable ZrSod2-22p to transport K+. Simultaneously, the
      P145(S/T) mutation decreased the antiporter transport activity for both Na+ and
      Li+. Replacement of Pro145 with glycine resulted in a ZrSod2-22p with extremely
      low activity only for Na+, and the exchange of a charged residue (Asp, Lys) for
      Pro145 completely stopped the activity. Mutagenesis of the corresponding proline
      in the S. cerevisiae Nha1 antiporter (Pro146) confirmed that this proline of the
      fifth transmembrane domain is a critical residue for antiporter function. This is
      the first evidence that a non-polar amino acid residue is important for the
      substrate specificity and activity of yeast Nha antiporters.

PMID- 15994325
TI  - Regions of Drosophila Notch that contribute to ligand binding and the modulatory
      influence of Fringe.
AB  - Two glycosyltransferases that transfer sugars to epidermal growth factor (EGF)
      domains, OFUT1 and Fringe, regulate Notch signaling. To characterize the impact
      of glycosylation at the 23 consensus O-fucose sites in Drosophila Notch, we
      conducted deletion mapping and site-specific mutagenesis and then assayed the
      binding of soluble forms of Notch to cell-surface ligands. Our results support
      the conclusion that EGF11 and EGF12 are essential for ligand binding, but
      indicate that other EGF domains also make substantial contributions to ligand
      binding. Characterization of Notch deletion constructs and O-fucose site mutants
      further revealed that no single site or region can account for the influence of
      Fringe on Notch-ligand binding. Additionally, we observed an influence of Fringe
      on a Notch fragment including only 4 of its 36 EGF domains (EGF10-13). Together,
      our observations imply that glycosylation influences Notch-ligand interactions
      through a distributive mechanism that involves local interactions with multiple
      EGF domains and led us to suggest a structural model for how Notch interacts with
      its ligands.

PMID- 15994324
TI  - A Leptospira interrogans enzyme with similarity to yeast Ste14p that methylates
      the 1-phosphate group of lipid A.
AB  - Distinct from other spirochetes, cells of Leptospira interrogans contain
      orthologues of all the Escherichia coli lpx genes required for lipid A
      biosynthesis, but they synthesize a modified form of lipopolysaccharide that
      supposedly activates toll-like receptor 2 (TLR2) instead of TLR4. The recent
      determination of the L. interrogans lipid A structure revealed an unprecedented O
      methylation of its 1-phosphate group (Que-Gewirth, N. L. S., Ribeiro, A. A.,
      Kalb, S. R., Cotter, R. J., Bulach, D. M., Adler, B., Saint Girons, I., Werts,
      C., and Raetz, C. R. H. (2004) J. Biol. Chem. 279, 25420-25429). The enzymatic
      activity responsible for selective 1-phosphate methylation has not been
      previously explored. A membrane enzyme that catalyzes the transfer of a methyl
      group from S-adenosylmethionine (SAM) to the 1-phosphate moiety of E. coli Kdo2
      [4'-(32)P]lipid A has now been discovered. The gene encoding this enzyme was
      identified based on the hypothesis that methylation of a phosphate group is
      chemically analogous to methylation of a carboxylate moiety at a membrane-water
      interface. Database searching revealed a candidate gene (renamed lmtA) in L.
      interrogans showing distant homology to the yeast isoprenylcysteine carboxyl
      methyltransferase, encoded by sterile-14, which methylates the a-type mating
      factor. Orthologues of lmtA were not present in E. coli, the lipid A of which
      normally lacks the 1-phosphomethyl group, or in other spirochetes, which do not
      synthesize lipid A. Expression of the lmtA gene behind the lac promoter on a low
      copy plasmid resulted in the appearance of SAM-dependent methyltransferase
      activity in E. coli inner membranes and methylation of about 30% of the
      endogenous E. coli lipid A. Inactivation of the ABC transporter MsbA did not
      inhibit methylation of newly synthesized lipid A. Methylated E. coli lipid A was
      analyzed by mass spectrometry and NMR spectroscopy to confirm the location of the
      phosphomethyl group at the 1-position. In human cells, engineered to express the
      individual TLR subtypes, 1-phosphomethyl-lipid A purified from lmtA-expressing E.
      coli potently activated TLR4 but not TLR2.

PMID- 15994326
TI  - Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras
      family small GTPases.
AB  - Although some members of Ras family small GTPases, including M-Ras, share the
      primary structure of their effector regions with Ras, they exhibit vastly
      different binding properties to Ras effectors such as c-Raf-1. We have solved the
      crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma
      imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras
      resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a
      distinctive switch I conformation, which is caused by impaired intramolecular
      interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector
      region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that
      H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2.
      Whereas state 2 is a predominant form of H-Ras and corresponds to the "on"
      conformation found in the complex with effectors, state 1 is thought to represent
      the "off" conformation, whose tertiary structure remains unknown. 31P NMR
      analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1
      conformation, which undergoes conformational transition to state 2 upon
      association with c-Raf-1. These results indicate that the solved structure of M
      Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state
      1 in M-Ras is likely to account for its weak binding ability to the Ras
      effectors, suggesting the importance of the tertiary structure factor in small
      GTPase-effector interaction. Further, the first determination of the state 1
      structure provides a molecular basis for developing novel anti-cancer drugs as
      compounds that hold Ras in the state 1 "off" conformation.

PMID- 15994327
TI  - ABCG1 redistributes cell cholesterol to domains removable by high density
      lipoprotein but not by lipid-depleted apolipoproteins.
AB  - ATP binding cassette transporter G1 (ABCG1) mediates the transport of cholesterol
      from cells to high density lipoprotein (HDL) but not to lipid-depleted
      apolipoprotein A-I. Here we show that human ABCG1 overexpressed in baby hamster
      kidney cells in the absence of lipoproteins traffics to the plasma membrane and
      redistributes membrane cholesterol to cell-surface domains accessible to
      treatment with the enzyme cholesterol oxidase. Cholesterol removed by HDL was
      largely derived from these domains in ABCG1 transfectants but not in cells
      lacking ABCG1. Overexpression of ABCG1 also increased cholesterol esterification,
      which was decreased by the addition of HDL, suggesting that a proportion of the
      cell-surface cholesterol not removed by HDL is transported to the intracellular
      esterifying enzyme acyl-CoA:cholesterol acyltransferase. A 638-amino acid ABCG1,
      which lacked the 40 N-terminal amino acids of the predicted full-length protein,
      was fully functional and of a similar size to ABCG1 expressed by cholesterol
      loaded human monocyte-derived macrophages. Mutating an essential glycine residue
      in the Walker A motif abolished ABCG1-dependent cholesterol efflux and
      esterification and prevented localization of ABCG1 to the cell surface,
      indicating that the ATP binding domain in ABCG1 is essential for both lipid
      transport activity and protein trafficking. These studies show that ABCG1
      redistributes cholesterol to cell-surface domains where it becomes accessible for
      removal by HDL, consistent with a direct role of ABCG1 in cellular cholesterol
      transport.

PMID- 15994328
TI  - Structural and chemical requirements for histidine phosphorylation by the
      chemotaxis kinase CheA.
AB  - The CheA histidine kinase initiates the signal transduction pathway of bacterial
      chemotaxis by autophosphorylating a conserved histidine on its phosphotransferase
      domain (P1). Site-directed mutations of neighboring conserved P1 residues (Glu
      67, Lys-48, and His-64) show that a hydrogen-bonding network controls the
      reactivity of the phospho-accepting His (His-45) in Thermotoga maritima CheA. In
      particular, the conservative mutation E67Q dramatically reduces phosphotransfer
      to P1 without significantly affecting the affinity of P1 for the CheA ATP-binding
      domain. High resolution crystallographic studies revealed that although all
      mutants disrupt the hydrogen-bonding network to varying degrees, none affect the
      conformation of His-45. 15N-NMR chemical shift studies instead showed that Glu-67
      functions to stabilize the unfavored N(delta1)H tautomer of His-45, thereby
      rendering the N(epsilon2) imidazole unprotonated and well positioned for
      accepting the ATP phosphoryl group.

PMID- 15994329
TI  - Crystallographic study on the dioxygen complex of wild-type and mutant cytochrome
      P450cam. Implications for the dioxygen activation mechanism.
AB  - Two key amino acids, Thr252 and Asp251, are known to be important for dioxygen
      activation by cytochrome P450cam. We have solved crystal structures of a critical
      intermediate, the ferrous dioxygen complex (Fe(II)-O2), of the wild-type P450cam
      and its mutants, D251N and T252A. The wild-type dioxygen complex structure is
      very much the same as reported previously (Schlichting, I., Berendzen, J., Chu,
      K., Stock, A. M., Maves, S. A., Benson, D. E., Sweet, R. M., Ringe, D., Petsko,
      G. A., and Sligar, S. G. (2000) Science 287, 1615-1622) with the exception of
      higher occupancy and a more ordered structure of the iron-linked dioxygen and two
      "catalytic" water molecules that form part of a proton relay system to the iron
      linked dioxygen. Due to of the altered conformation of the I helix groove these
      two waters are missing in the D251N dioxygen complex which explains its lower
      catalytic activity and slower proton transfer to the dioxygen ligand. Similarly,
      the T252A mutation was expected to disrupt the active site solvent structure
      leading to hydrogen peroxide formation rather than substrate hydroxylation.
      Unexpectedly, however, the two "catalytic" waters are retained in the T252A
      mutant. Based on these findings, we propose that the Thr(252) accepts a hydrogen
      bond from the hydroperoxy (Fe(III)-OOH) intermediate that promotes the second
      protonation on the distal oxygen atom, leading to O-O bond cleavage and compound
      I formation.

PMID- 15994330
TI  - The Prp19-associated complex is required for specifying interactions of U5 and U6
      with pre-mRNA during spliceosome activation.
AB  - Activation of the spliceosome involves a major structural change in the
      spliceosome, including release of U1 and U4 small nuclear ribonucleoprotein
      particles and the addition of a large protein complex, the Prp19-associated
      complex. We previously showed that the Prp19-associated complex is required for
      stable association of U5 and U6 with the spliceosome after U4 is released.
      Changes within the spliceosome upon binding of the Prp19-associated complex
      include remodeling of the U6/5' splice site interaction and destabilization of
      Lsm proteins to allow further interaction of U6 with the intron sequence. Here,
      we further analyzed interactions of U5 and U6 with pre-mRNA at various stages of
      spliceosome assembly from initial binding of tri-small nuclear ribonucleoprotein
      complex to the activated spliceosome to reveal stepwise changes of interactions.
      We demonstrate that both U5 and U6 interacted with pre-mRNA in dynamic manners
      spanning over a large region of U6 and the 5' exon sequences prior to the
      activation of the spliceosome. During spliceosome activation, interactions were
      locked down to small regions, and the Prp19-associated complex was required for
      defining the specificity of interaction of U5 and U6 with the 5' splice site to
      stabilize their association with the spliceosome after U4 is dissociated.

PMID- 15994331
TI  - Ligand-induced dimer-tetramer transition during the activation of the cell
      surface epidermal growth factor receptor-A multidimensional microscopy analysis.
AB  - The epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine
      kinase family of receptors. For many years it has been believed that receptor
      activation occurs via a monomer-dimer transition that is associated with a
      conformational change to activate the kinase. However, little is known about the
      quaternary state of the receptor at normal levels of expression (<10(5)
      receptors/cell). We employed multidimensional microscopy techniques to gain
      insight into the state of association of the human EGFR, in the absence and
      presence of ligand, on the surface of intact BaF/3 cells (50,000 receptors/cell).
      Image correlation microscopy of an EGFR-enhanced green fluorescent protein
      chimera was used to establish an average degree of aggregation on the submicron
      scale of 2.2 receptors/cluster in the absence of ligand increasing to 3.7
      receptors/cluster in the presence of ligand. Energy transfer measurements between
      mixtures of fluorescein isothiocyanate-EGF and Alexa 555-EGF were performed using
      fluorescence lifetime imaging microscopy as a function of the donor: acceptor
      labeling ratio to gain insight into the spatial disposition of EGFR ligand
      binding sites on the nanometer scale. In the context of a two-state Forster
      resonance energy transfer (FRET)/non-FRET model, the data are consistent with a
      minimum transfer efficiency of 75% in the FRET population. The microscopy data
      are related to biophysical data on the EGFR in the A431 cell line and the three
      dimensional structure of the ligated EGFR extracellular domain. In the context of
      a monomer-dimer-oligomer model, the biophysical data are consistent with a
      significant fraction of ligated EGFR tetramers comprising two dimers juxtaposed
      in a side-by-side (or slightly staggered) arrangement. Our data are consistent
      with a specific higher order association of the ligand-bound EGFR on the
      nanometer scale and indicate the existence of distinct signaling entities beyond
      the level of the EGFR dimer which could play an important role in receptor
      transactivation.

PMID- 15994332
TI  - Interaction with PDZK1 is required for expression of organic anion transporting
      protein 1A1 on the hepatocyte surface.
AB  - Although many organic anion transport protein (Oatp) family members have PDZ
      consensus binding sites at their C termini, the functional significance is
      unknown. In the present study, we utilized rat Oatp1a1 (NM_017111) as a
      prototypical member of this family to examine the mechanism governing its
      subcellular trafficking. A peptide corresponding to the C-terminal 16 amino acids
      of rat Oatp1a1 was used to affinity-isolate interacting proteins from rat liver
      cytosol. Protein mass fingerprinting identified PDZK1 as the major interacting
      protein. This was confirmed by immunoprecipitation of an Oatp1a1-PDZK1 complex
      from cotransfected 293T cells as well as from native rat liver membrane extracts.
      Oatp1a1 bound predominantly to the first and third PDZ binding domains of PDZK1,
      whereas the high density lipoprotein receptor, scavenger receptor B type I binds
      to the first domain. Although it is possible that PDZK1 forms a complex with
      these two integral membrane proteins, this did not occur, suggesting that as yet
      undescribed factors lead to selectivity in the interaction of these protein
      ligands with PDZK1. Oatp1a1 protein expression was near normal in PDZK1 knock-out
      mouse liver. However, it was located predominantly in intracellular structures,
      in contrast to its normal basolateral plasma membrane distribution. Plasma
      disappearance of the Oatp1a1 ligand [35S]sulfobromophthalein was correspondingly
      delayed in knock-out mice. These studies show a critical role for oligomerization
      of Oatp1a1 with PDZK1 for its proper subcellular localization and function.
      Because its ability to transport substances into the cell requires surface
      expression, this must be considered in any assessment of physiologic function.

PMID- 15994333
TI  - Pseudoapoptosis induced by brief activation of ATP-gated P2X7 receptors.
AB  - P2X7 receptors are ATP-gated ion channels primarily expressed on antigen
      presenting immune cells where they play a role in the acute inflammatory
      response. These ion channels couple not only to influx of cations, including
      calcium, but also to rapid alterations in cell morphology (membrane blebbing,
      phosphatidylserine exposure, microvesicle shedding). These features resemble the
      extranuclear events associated with end stages of apoptosis but cell death does
      not occur if receptor activation is brief. Here we delineate two signaling
      pathways underlying these apoptotic-like processes. Loss of membrane asymmetry
      occurs within seconds, which directly triggers cytoskeletal disruption and
      zeiotic membrane blebbing; this is readily reversible and requires both calcium
      influx through P2X7 channels and mitochondrial calcium increase but is not
      associated with cytochrome c release. A slower, calcium-independent, ROCK-1
      dependent cascade that does not involve rapid loss of membrane asymmetry but is
      associated with cytochrome c release is secondarily activated. The ROCK-1 pathway
      appears largely responsible for cell death, which occurs after prolonged
      stimulation of P2X7 receptors. We suggest that the former mechanism underlies the
      reversible pseudoapoptotic events induced by brief activation of P2X7 receptors.

PMID- 15994334
TI  - Activation of NF-kappaB by extracellular matrix is involved in spreading and
      glucose-stimulated insulin secretion of pancreatic beta cells.
AB  - Laminin-5-rich extracellular matrix derived from 804G cells (804G-ECM) engages
      beta1 integrins to induce spreading, improve glucose-stimulated insulin secretion
      (GSIS), and increase survival of pancreatic beta cells. The present study
      examines whether 804G-ECM activates the transcriptional activity of NF-kappaB and
      the involvement of NF-kappaB in those effects of 804G-ECM on pancreatic beta
      cells. 804G-ECM induces nuclear translocation and the DNA binding activity of the
      p65 subunit of NF-kappaB. 804G-ECM-induced nuclear translocation of NF-kappaB was
      weak as compared with that induced by interleukin-1beta. Transient 804G-ECM
      induced DNA binding activity of NF-kappaB (peak at 2 h) and overexpression of NF
      kappaB target genes IkappaB alpha and NF-kappaB1(p105) (peak at 4 h) were
      observed. When NF-kappaB was inhibited by an inhibitor of IkappaB alpha
      phosphorylation (Bay 11-7082) or by a recombinant adenovirus expressing the
      nonphosphorylatable form of IkappaB alpha, 804G-ECM-induced cell spreading and
      actin cytoskeleton organization were reduced. GSIS from cells on 804G-ECM was
      inhibited 5-fold, whereas cell survival was not affected. In summary, the results
      indicate that 804G-ECM induces a transient and moderate NF-kappaB activity. This
      study shows for the first time that ECM-induced NF-kappaB activity is necessary
      in maintaining GSIS, although it does not affect survival of pancreatic beta
      cells. The effects of ECM-induced NF-kappaB activity contrast with the
      deleterious effects of cytokine-induced NF-kappaB activity. It is proposed that
      transient and moderate NF-kappaB activity is essential for proper function of the
      pancreatic beta cell.

PMID- 15994335
TI  - Activation of M1 muscarinic acetylcholine receptors stimulates the formation of a
      multiprotein complex centered on TRPC6 channels.
AB  - In this study we showed that stimulation of M1 muscarinic acetylcholine receptors
      (mAChRs) activates endogenous transient receptor potential-canonical, subtype 6
      (TRPC6), channels in neuronal PC12D cells. Activation of TRPC6 channels is
      correlated with the formation of a multiprotein complex containing M1 mAChRs,
      TRPC6 channels, and protein kinase C (PKC). Formation of the M1 mAChR-TRPC6-PKC
      complex is transient, with highest levels reached approximately 2 min after
      stimulation of M1 mAChRs. PKC in the complex phosphorylates TRPC6 on a conserved
      serine residue in the carboxyl-terminal domain (Ser768 in the TRPC6A isoform and
      Ser714 in the TRPC6B isoform). The immunophilin FKBP12, the phosphatase
      calcineurin, and Ca2+-binding protein calmodulin are also recruited to the M1
      mAChR-TRPC6-PKC complex following activation of M1 mAChRs and remain stably
      associated with the TRPC6 channels after M1 mAChRs and PKC have disassociated.
      Binding of FKBP12, calcineurin, and calmodulin to TRPC6 channels is blocked by
      the following: 1) inhibition of PKC; 2) mutation of the PKC phosphorylation site
      (Ser(7168/714)) in the channels; or 3) pretreatment with FK506 or rapamycin,
      immunosuppressants that directly bind FKBP12. Inhibition of FKBP12 binding blocks
      the dephosphorylation of TRPC6 channels and the disassociation of M1 mAChRs,
      without affecting disassociation of PKC. The calcineurin inhibitor cyclosporin A
      also blocks the dephosphorylation of TRPC6 and prevents the disassociation of M1
      mAChRs. Together, these results show that activated TRPC6 channels form the
      center of a dynamic multiprotein complex that includes PKC and calcineurin, which
      respectively phosphorylate and dephosphorylate the channels. Phosphorylation of
      the TRPC6 channels by PKC is required for the binding of FKBP12, which in turn is
      required for the binding of calcineurin and calmodulin. Subsequent
      dephosphorylation of the channels by calcineurin is required for the
      disassociation of M1 mAChRs.

PMID- 15994337
TI  - Multidisciplinary care of the pediatric oncology patient.

PMID- 15994338
TI  - Osteogenic sarcoma of the sacral spine: an interdisciplinary team challenge.
AB  - A child with osteogenic sarcoma of the sacral spine has complex nursing and
      interdisciplinary team needs. The course of one patient is discussed, both from
      the patient and family's perspective and that of her inter-disciplinary care
      team. The need for a coordinated, holistic approach to care that involves advance
      planning, continual reassessment of goals, and clear communication among the team
      members and consulting services is clearly demonstrated.

PMID- 15994339
TI  - Tell me about it: drawing as a communication tool for children with cancer.
AB  - As health-related research on children shifts from seeking information about
      children to seeking information directly from them, researchers recognize the
      need for developmentally appropriate methods such as drawing to help children
      communicate their experiences. This international study sought to (a) explore and
      compare the nature of stressors of everyday life and disease that children with
      cancer in the United Kingdom and the United States experience, (b) explore and
      compare the coping measures they use to manage these stressors, and (c) examine
      the use of drawing to enhance communication. Participants included 22 children
      ages 7 to 18 years, 13 boys and 9 girls receiving treatment for cancer in the
      United Kingdom and the United States. Quantitative and qualitative methods were
      used within a grounded theory approach and included drawing to accompany the
      traditional grounded theory methods of interview and observation. Findings
      indicate that children, regardless of their ethnicity and other cultural
      components, respond to the childhood cancer experience in a similar manner. The
      use of drawing enhanced communication through direct visual expression and/or
      through verbal expression via the "campfire effect."

PMID- 15994340
TI  - Sibling involvement at the end of life.
AB  - When a child is diagnosed with a life-threatening illness, such as cancer, there
      is much disruption to the family. It is a struggle for parents to divide their
      time between the hospital, home, and other healthy siblings. Nurses strive to
      provide family-centered care, which involves siblings in many stages of the
      treatment process. However, during the terminal phase of a child's disease, the
      dying child and the parents are often the sole focus of the health care team.
      Siblings are often left to stay with extended family members or friends so that
      they are protected from the reality of death. However, previous research has
      shown that even young children understand death, and some of the protective
      measures parents take actually hamper the siblings'bereavement process. Nurses
      are in a position to guide families through the emotional time of a child's death
      while advocating for sibling involvement at a level appropriate for their
      developmental stage.

PMID- 15994341
TI  - Siblings' needs and issues when a brother or sister dies of cancer.
AB  - To explore siblings'needs and issues when a brother or sister dies of cancer,
      interviews were conducted with 10 surviving children and young adults. The
      siblings expressed dissatisfaction with the information they had received and
      said that they had not felt involved in the dying process with the exception of
      the terminal period. The siblings stated that their dissatisfaction would have
      been reduced if doctors and nurses had provided continuous information and
      support. Loneliness, anxiety, anger, and jealousy were common feelings that they
      expressed. Friends and school were important to the siblings, representing a
      normal environment free from the domination of sickness. The siblings also
      expressed that they needed to mourn in their own way including periods of time
      when they did not mourn. The absence of the dead sibling was felt particularly
      during family celebrations. The siblings continued to have special memories and
      objects, and all still included the dead sibling as a member in the family.

PMID- 15994342
TI  - Double leptin and melanocortin-4 receptor gene mutations have an additive effect
      on fat mass and are associated with reduced effects of leptin on weight loss and
      food intake.
AB  - Melanocortin-4 receptors (MC4Rs) are involved in the regulation of food intake,
      sympathetic nervous activity, and adrenal and thyroid function by leptin. The
      role of MC4Rs in regulating energy balance by leptin was investigated using
      double heterozygote or homozygous leptin (Lep(ob)) and Mc4r gene mutant mice.
      Double heterozygous or homozygous mutants were generated by crossing MC4R
      knockout (Mc4r-/-) mice, backcrossed onto C57BL/6J, with B6.V-Lep(ob) mice.
      Energy expenditure was measured using indirect calorimetry. The effect of leptin
      on food intake, weight loss, insulin, and corticosterone was compared for
      Lep(ob)/Lep(ob)Mc4r-/- mice and Lep(ob)/Lep(ob) mice. Double heterozygous and
      homozygous mutants exhibited an additive effect on fat mass. The 2-fold increase
      in body weight associated with severe obesity of Lep(ob)/Lep(ob) mice was
      associated with a significantly higher 24 h total and resting energy expenditure.
      The effect of obesity on energy expenditure was attenuated by 50% in
      Lep(ob)/Lep(ob) Mc4r+/- and Lep(ob)/Lep(ob) Mc4r-/- mice. Loss of MC4Rs did not
      affect basal food intake of Lep(ob)/Lep(ob) mice but was associated with partial
      leptin resistance in terms of food intake and weight loss. Leptin suppression of
      insulin and corticosterone in Lep(ob)/Lep(ob) mice were not significantly
      affected by Mc4r genotype. These results suggest a complex interaction between
      the Lep and Mc4r genes in energy homeostasis and suggest that MC4Rs retain
      significant anti-obesity function in the obese leptin-deficient state. Increased
      adiposity with double mutations may involve a reduction in energy expenditure.
      MC4Rs might have a modest role in the regulation of energy balance by exogenously
      administered leptin, primarily effecting food intake.

PMID- 15994343
TI  - Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of
      glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular
      neurons.
AB  - Glucocorticoids secreted in response to stress activation of the hypothalamic
      pituitary-adrenal axis feed back onto the brain to rapidly suppress
      neuroendocrine activation, including oxytocin and vasopressin secretion. Here we
      show using whole-cell patch clamp recordings that glucocorticoids elicit a rapid,
      opposing action on synaptic glutamate and gamma-aminobutyric acid (GABA) release
      onto magnocellular neurons of the hypothalamic supraoptic nucleus and
      paraventricular nucleus, suppressing glutamate release and facilitating GABA
      release by activating a putative membrane receptor. The glucocorticoid effect on
      both glutamate and GABA release was blocked by inhibiting postsynaptic G protein
      activity, suggesting a dependence on postsynaptic G protein signaling and the
      involvement of a retrograde messenger. Biochemical analysis of hypothalamic
      slices treated with dexamethasone revealed a glucocorticoid-induced rapid
      increase in the levels of the endocannabinoids anandamide (AEA) and 2
      arachidonoylglycerol (2-AG). The glucocorticoid suppression of glutamate release
      was blocked by the type I cannabinoid receptor cannabinoid receptor antagonist,
      AM251, and was mimicked and occluded by AEA and 2-AG, suggesting it was mediated
      by retrograde endocannabinoid release. The glucocorticoid facilitation of GABA
      release was also blocked by AM251 but was not mimicked by AEA, 2-AG, or a
      synthetic cannabinoid, WIN 55,212-2, nor was it blocked by vanilloid or
      ionotropic glutamate receptor antagonists, suggesting that it was mediated by a
      retrograde messenger acting at an AM251-sensitive, noncannabinoid/nonvanilloid
      receptor at presynaptic GABA terminals. The combined, opposing actions of
      glucocorticoids mediate a rapid inhibition of the magnocellular neuroendocrine
      cells, which in turn should mediate rapid feedback inhibition of the secretion of
      oxytocin and vasopressin by glucocorticoids during stress activation of the
      hypothalamic-pituitary-adrenal axis.

PMID- 15994344
TI  - Stimulation of resorption in cultured mouse calvarial bones by
      thiazolidinediones.
AB  - Dosage-dependent release of 45Ca was observed from prelabeled mouse calvarial
      bones after treatment with two thiazolidinediones, troglitazone and ciglitazone.
      Release of 45Ca by ciglitazone was decreased by the osteoclast inhibitors
      acetazolamide, calcitonin, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, and
      IL-4, but not affected by the peroxisome proliferator-activated receptor gamma
      antagonist, GW 9662, the mitotic inhibitor, hydroxyurea, or indomethacin.
      Enhanced expression of receptor activator of nuclear factor-kappaB ligand (RANKL)
      mRNA and protein and decreased osteoprotegerin (OPG) mRNA and protein were noted
      after ciglitazone treatment of calvariae. Ciglitazone and RANKL each caused
      increased mRNA expression of osteoclast markers: calcitonin receptor, tartrate
      resistant acid phosphatase, cathepsin K, matrix metalloproteinase-9, integrin
      beta3, and nuclear factor of activated T cells 2. OPG inhibited mRNA expression
      of RANKL stimulated by ciglitazone, mRNA expression of osteoclast markers
      stimulated by ciglitazone and RANKL, and 45Ca release stimulated by troglitazone
      and ciglitazone. Increased expression of IL-1alpha mRNA by ciglitazone was not
      linked to resorption stimulated by the thiazolidinedione. Ciglitazone did not
      increase adipogenic gene expression but enhanced osteocalcin mRNA in calvariae.
      In addition to exhibiting sensitivity to OPG, data indicate that stimulation of
      osteoclast differentiation and activity by thiazolidinediones may occur by a
      nonperoxisome proliferator-activated receptor gamma-dependent pathway that does
      not require cell proliferation, prostaglandins, or IL-1alpha but is characterized
      by an increased RANKL to OPG ratio.

PMID- 15994345
TI  - Attenuation of preoptic area glutamate release correlates with reduced
      luteinizing hormone secretion in middle-aged female rats.
AB  - Glutamate (Glu) and its receptors are involved in the maturation and maintenance
      of the neural mechanisms governing the preovulatory LH surge of young,
      reproductive-aged rodents and nonhuman primates. Little is known about the role
      of Glu in the delayed onset and reduced peak amplitude of the LH surge that
      characterizes female rodents during early reproductive senescence. The present
      study tested the hypothesis that the delayed and attenuated LH surge observed in
      middle-aged female rats is associated with altered hypothalamic Glu release. We
      used intracerebral microdialysis in young (3-4 months) and middle-aged (9-11
      months) female rats to monitor changes in medial preoptic area Glu release and
      jugular vein catheters to monitor changes in serum LH levels. All animals were
      ovariectomized and injected with estradiol and progesterone in doses sufficient
      to produce a robust LH surge in most (approximately 70%) young rats. In both
      young and middle-aged females that surged, extracellular Glu levels were higher
      than in those that did not surge. Among animals that surged, the onset of the LH
      surge was significantly delayed, and the amplitude of the surge was significantly
      reduced in middle-aged compared with young rats. Middle-aged females also had
      significantly reduced extracellular Glu levels throughout the day of the LH surge
      when compared with young females. These data strongly suggest that age-related
      hypothalamic dysfunction contributes to reproductive aging independent of gonadal
      failure. We propose that reduced medial preoptic area Glu transmission
      contributes to reproductive aging by attenuating excitatory input to GnRH
      neurons.

PMID- 15994346
TI  - Insulin-like growth factor binding protein-2 binding to extracellular matrix
      plays a critical role in neuroblastoma cell proliferation, migration, and
      invasion.
AB  - IGF binding proteins (IGFBPs) modulate IGF cellular bioavailability and may
      directly regulate tumor growth and invasion. We have previously shown that IGFBP
      2 binds and localizes IGF-I to the pericellular matrix and have provided some
      evidence suggesting that the heparin binding domain (HBD) or the arginine-glycine
      aspartic acid (RGD) integrin binding motif may be involved in these interactions.
      However, the precise mechanisms involved remain to be elucidated. We therefore
      mutated the HBD or RGD sequence of IGFBP-2 and investigated consequent effects on
      extracellular matrix (ECM) binding, IGF-induced proliferation, and migration of
      neuroblastoma cells. IGFBP-2 and its arginine-glycine-glutamic acid (RGE) mutant
      similarly bound ECM components, whereas binding of mutant HBD-IGFBP-2 to each of
      the ECM substrates was markedly reduced by 70-80% (P < 0.05). IGF-I (100 ng/ml)
      increased incorporation of 3H-thymidine in neuroblastoma SK-N-SHEP cells by
      approximately 30%, an effect blunted by exogenously added native or either mutant
      IGFBP-2. Overexpression of IGFBP-2 and its RGE mutant potently promoted SHEP cell
      proliferation (5-fold), whereas SHEP cell proliferation was negligible when HBD
      IGFBP-2 was overexpressed. Addition or overexpression of IGFBP-2 and its RGE
      mutant potently (P < 0.05) enhanced SHEP cell migration/invasion through the ECM.
      However, overexpression of the HBD-IGFBP-2 mutant potently inhibited (50-60%)
      SHEP cell invasion through ECM. Thus, IGFBP-2, which binds to the ECM, enhances
      proliferation and metastatic behavior of neuroblastoma cells, functions that
      directly or indirectly use the HBD but not the integrin binding sequence. Our
      novel findings thus point to a key role for the HBD of IGFBP-2 in the control and
      regulation of neuroblastoma growth and invasion.

PMID- 15994347
TI  - Glucose dependence of the regulated secretory pathway in alphaTC1-6 cells.
AB  - We have investigated the effects of chronically elevated glucose concentrations
      on the pancreatic alpha-cell line alphaTC1-6. We show that basal glucagon
      secretion and proglucagon gene expression were increased in response to high
      glucose levels. The extent of acute stimulated secretion of glucagon was also
      increased in response to high glucose, as was the transcription of the prohormone
      processing enzymes PC1/3 and PC2. The secretion of GLP-1, a proglucagon-derived
      peptide produced by cleavage of proglucagon by PC1/3, was also increased in
      response to high glucose. Gene expression profiling experiments showed that a
      number of components of the regulated secretory pathway were up-regulated at high
      glucose concentrations, including processing enzymes and exocytotic proteins.
      Immunoblot analysis showed that the expression of the exocytotic SNARE proteins,
      as well as that of PC1/3, chromogranin A, and 7B2, were all increased after
      chronic exposure to high glucose levels. Immunocytochemistry showed no changes in
      the expression of the mature alpha-cell markers glucagon and brn-4 and no
      induction of the immature alpha-cell marker pdx-1. We conclude that chronically
      elevated glucose concentrations up-regulate the regulated secretory response of
      the alpha-cell.

PMID- 15994348
TI  - Direct agonist/antagonist functions of dehydroepiandrosterone.
AB  - Dehydroepiandrosterone (DHEA) exhibits peak adrenal secretion in the fetus at
      term and around age 30 yr in the adult. Levels then progressively decline, which
      is associated with decreased levels of testosterone, dihydrotestosterone, and
      estrogen in peripheral tissues. DHEA supplementation in postmenopausal women
      increases bone formation and density, an effect mainly attributed to peripheral
      conversion to sex hormones. In this study, we tested DHEA for direct effects on
      the androgen (AR) and estrogen (ER) receptors. DHEA bound to AR with a Ki of 1
      microM, which was associated with AR transcriptional antagonism on both the mouse
      mammary tumor virus and prostate-specific antigen promoters, much like the
      effects of bicalutamide. Unlike bicalutamide, DHEA stimulated, rather than
      inhibited, LNCaP cell growth, suggesting possible interaction with other hormone
      receptors. Indeed DHEA bound to ERalpha and ERbeta, with Ki values of 1.1 and 0.5
      microM, respectively. Despite the similar binding affinities, DHEA showed
      preferential agonism of ERbeta with an EC50 of approximately 200 nm and maximal
      activation at 1 microM. With ERalpha we found 30-70% agonism at 5 microM,
      depending on the assay. Physiological levels of DHEA are approximately 30 nM and
      up to 90 nM in the prostate. DHEA at 30 nM is actually sufficient to activate
      ERbeta transcription to the same degree as estrogen at its circulating
      concentration, and additive effects are seen when the two were combined. Taken
      together, DHEA has the potential for physiologically relevant direct activation
      of ERbeta. With peak levels at term and age 30 yr, there is also a potential for
      antagonist effects on AR and partial agonism of ERalpha.

PMID- 15994349
TI  - Pathways of vitamin A delivery to the embryo: insights from a new tunable model
      of embryonic vitamin A deficiency.
AB  - Circulating retinoids (vitamin A and its derivatives) are found predominantly as
      retinol bound to retinol-binding protein (RBP), which transports retinol from
      liver stores to target tissues, or as retinyl ester incorporated in lipoproteins
      of dietary origin. The transport of retinoids from maternal to fetal circulation
      is poorly understood, especially under conditions of inadequate dietary vitamin A
      intake. Here we present RBP-/- mice as a tunable model of embryonic vitamin A
      deficiency. This model has enabled us to analyze metabolic links between maternal
      nutrition and retinoid delivery to the fetus. Our data show that retinol-RBP is
      the primary contributor to fetal development, whereas retinyl ester are largely
      responsible for accumulation of fetal retinoid stores. Furthermore, these studies
      indicate the importance of embryonic RBP in distributing vitamin A to certain
      developing tissues under restrictive diets. We also show differences among
      developing tissues in their dependency on the embryonic retinol-RBP pathway.
      Finally, we demonstrate that accumulation of embryonic vitamin A stores does not
      depend on the expression of RBP in the fetal liver.

PMID- 15994350
TI  - Targeted overexpression of leptin to keratinocytes in transgenic mice results in
      lack of skin phenotype but induction of early leptin resistance.
AB  - The epidermis has a great potential as a bioreactor to produce proteins with
      systemic action. However, the consequences of ectopic epidermal protein
      overexpression need to be carefully addressed to avoid both local and systemic
      adverse effects. Thus, the long-term effects of leptin on skin physiology have
      not been studied, and the metabolic consequences of sustained keratinocyte
      derived leptin overexpression are unknown. Herein we describe that very high
      serum leptin levels can be achieved from a cutaneous source in transgenic mice in
      which leptin cDNA overexpression was driven by the keratin K5 gene regulatory
      sequences. Histopathological analysis including the study of skin differentiation
      and proliferation markers in these transgenic mice revealed that keratinocyte
      derived leptin overexpression appears not to have any impact on cutaneous
      homeostasis. Although young K5-leptin transgenic mice showed remarkable thinness
      and high glucose metabolism as shown in other leptin transgenic mouse models, a
      marked leptin insensitivity become apparent as early as 3-4 months of age as
      demonstrated by increased weight gain and insulin resistance development. Other
      signs of leptin/insulin resistance included increased bone mass, organomegaly,
      and wound healing impairment. In addition, to provide evidence for the lack of
      untoward effects of leptin on epidermis, this transgenic mouse helps us to
      establish the safe ranges of keratinocyte-derived leptin overexpression and may
      be useful as a model to study leptin resistance.

PMID- 15994351
TI  - Role of endothelin-1 in the migration of human olfactory gonadotropin-releasing
      hormone-secreting neuroblasts.
AB  - FNC-B4 neuroblasts that express both neuronal and olfactory markers have been
      established and cloned. These cells express GnRH and both the endothelin-1 (ET-1)
      gene and protein and respond in a migratory manner to GnRH in a dose-dependent
      manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1
      by regulating the secretion of GnRH through endothelin type A receptors and by
      stimulating their proliferation through endothelin type B (ETB) receptors. In
      this study, we found that FNC-B4 cells are able to migrate in response to ET-1
      through the involvement of ETB receptors. Combined immunohistochemical and
      biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and
      a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor
      antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor
      antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were
      independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1,
      through ETB receptor activation, may be required to maintain an adequate
      proliferative stem cell pool in the developing olfactory epithelium and the
      subsequent commitment to GnRH neuronal migratory pattern. The coordinate
      interaction between ET receptors and GnRH receptor participates in the fully
      expressed GnRH-secreting neuron phenotype.

PMID- 15994352
TI  - It's not NICE to discriminate.

PMID- 15994353
TI  - The challenge of Terri Schiavo: lessons for bioethics.
AB  - This essay reviews a range of issues arising from the complex case of Terri
      Schiavo and the lessons the case raises for bioethicists. It argues that embedded
      in the case is a broader controversy than is immediately evident, one involving
      the definitions by which bioethics judge cases of extreme physical and
      psychological limits, in its principled form of address. Further, it argues that
      bioethicists who assume the issues involved in the case are settled miss the
      point of the emotional responses it has brought forth.

PMID- 15994354
TI  - Justice and the NHS: a comment on Culyer.
AB  - The nature and significance of equity and equality in relation to health and
      healthcare policy is discussed in the light of a recent article by Culyer. Culyer
      makes the following claims: (a) the importance of equity in relation to the
      provision of health care derives from the human need for health in order to
      flourish; and (b) for the sake of equity, equality of health among the members of
      particular political jurisdictions should be the aim of health policy. Both these
      claims are challenged in this paper. The argument put forward is that it is only
      when needs arise and are met in particular contexts that need and equity are
      fused. The state and its agents and agencies should distribute what it
      distributes impartially, whatever it distributes. Whether or not equity applies
      to the distribution of healthcare services depends on how they are provided and
      not on their nature as "primary goods". Contrary to what Culyer suggests, a
      policy of trying to produce the outcome of health equality would be inequitable.
      It would not be impartial and it would fail to treat persons as persons ought to
      be treated.

PMID- 15994355
TI  - A request for hospice admission from hospital to withdraw ventilation.
AB  - A request to admit a hospital inpatient with motor neurone disease to the hospice
      generated unusual unease. Significantly, withdrawal of ventilation had already
      been planned. The presumption that ventilation would be withdrawn after transfer
      presented a dilemma. Should the hospice accept the admission? If so, should the
      hospice staff stop the ventilation, and then when and how? Debate centred on the
      continuity of best interests and the logistics of withdrawing ventilation. The
      factors making the request contentious identified competing interests within
      hospice admission decision making that could detrimentally impact on patient
      care.

PMID- 15994356
TI  - Informed consent, participation in, and withdrawal from a population based cohort
      study involving genetic analysis.
AB  - OBJECTIVE: Population based cohort studies involving genetic research have been
      initiated in several countries. However, research published to date provides
      little information on the willingness of the general population to participate in
      such studies. Furthermore, there is a need to discover the optimal methods for
      acquiring fully informed consent from the general population. We therefore
      examined the results of a population based genetic cohort study to identify the
      factors affecting the participation rate by members of the general public and
      also specifically to examine the impact of different consent procedures on the
      rate of participation by prospective candidates and their subsequent withdrawal
      rate from the study. DESIGN: Descriptive analyses. SETTING AND PARTICIPANTS: The
      study evaluated two non-genetic subcohorts comprising 3166 people attending for a
      health checkup during 2002, and two genetic subcohorts comprising 2195 people who
      underwent a checkup during 2003. MAIN OUTCOME MEASUREMENTS: Analysis endpoints
      were differences in participation rates between the non-genetic and genetic
      subcohorts, differences between providing non-extensive and extensive preliminary
      information, and changes in participation status between baseline and at 6
      months. RESULTS: Participation rates in the genetic subcohorts were 4.7-9.3%
      lower than those in the non-genetic subcohorts. The odds ratios (OR) of
      participation in genetic research were between 0.60 and 0.77, and the OR for
      withdrawal from the research was over 7.70; providing preliminary extensive
      information about genetic research reduced the withdrawal risks (OR 0.15 for all
      dependent variables) but worsened participation rates (OR 0.63-0.74).
      CONCLUSIONS: The general population responded sceptically towards genetic
      research. It is crucial that genetic researchers utilise an informative and
      educational consent process worthy of public trust.

PMID- 15994358
TI  - Making regulations and drawing up legislation in Islamic countries under
      conditions of uncertainty, with special reference to embryonic stem cell
      research.
AB  - Stem cell research is a newly emerging technology that promises a wide variety of
      benefits for humanity. It has, however, also caused much ethical, legal, and
      theological debate. While some forms of its application were prohibited in the
      beginning, they have now started to be used in many countries. This fact obliges
      us to discuss the regulation of stem cell research at national and international
      level. It is obvious that in order to make regulations and to draw up legislation
      at national or international levels it helps to know the perspectives of
      different cultures and faith traditions. In this article the issue is explored
      from an Islamic perspective. Firstly, some basic information is given about Islam
      to explain how laws are drawn up and regulations made in this tradition.
      Secondly, the principles on which the laws and regulations are based are applied
      to stem cell research, and finally the permitted and prohibited methods of stem
      cell research are described. The discussions throughout the paper demonstrate
      that while some ethicists argue that stem cell research is unethical in the
      Islamic tradition, tradition permits it as long as such research is aimed at
      improving human health.

PMID- 15994357
TI  - Newborn screening: new developments, new dilemmas.
AB  - Scientific and technological advances are lending pressure to expand the scope of
      newborn screening. Whereas this has great potential for improving child health,
      it also challenges our current perception of such programmes. Standard newborn
      screening programmes are clearly justified by the fact that early detection and
      treatment of affected individuals avoids significant morbidity and mortality.
      However, proposals to expand the scope and complexity of such testing are not all
      supported by a similar level of evidence for unequivocal benefit. We argue that
      screening for genetic susceptibility to complex disorders is inherently different
      from standard screening and, while of potential value, must be considered
      separately from conventional testing.

PMID- 15994359
TI  - The physician charter on medical professionalism: a Jewish ethical perspective.
AB  - The physician charter on medical professionalism creates standards of ethical
      behaviour for physicians and has been endorsed by professional organisations
      worldwide. It is based on the cardinal principles of the primacy of patient
      welfare, patient autonomy, and social welfare. There has been little discussion
      in the bioethics community of the doctrine of the charter and none from a Jewish
      ethical perspective. In this essay the authors discuss the obligations of the
      charter from a Jewish ethical viewpoint and call on other cultures to develop
      their own unique perspectives on this important document.

PMID- 15994360
TI  - Does it matter that organ donors are not dead? Ethical and policy implications.
AB  - The "standard position" on organ donation is that the donor must be dead in order
      for vital organs to be removed, a position with which we agree. Recently, Robert
      Truog and Walter Robinson have argued that (1) brain death is not death, and (2)
      even though "brain dead" patients are not dead, it is morally acceptable to
      remove vital organs from those patients. We accept and defend their claim that
      brain death is not death, and we argue against both the US "whole brain"
      criterion and the UK "brain stem" criterion. Then we answer their arguments in
      favour of removing vital organs from "brain dead" and other classes of comatose
      patients. We dispute their claim that the removal of vital organs is morally
      equivalent to "letting nature take its course", arguing that, unlike "allowing to
      die", it is the removal of vital organs that kills the patient, not his or her
      disease or injury. Then, we argue that removing vital organs from living patients
      is immoral and contrary to the nature of medical practice. Finally, we offer
      practical suggestions for changing public policy on organ transplantation.

PMID- 15994361
TI  - The use of generic or patent medicines in the Netherlands.

PMID- 15994362
TI  - Stopping trials early for commercial reasons: the risk-benefit relationship as a
      moral compass.
AB  - Decisions by industry sponsors to end clinical trials early for commercial
      reasons have been the subject of controversy. I argue that the principal
      consideration in assessing these decisions ought to be the way in which the
      termination would affect the trial's risk-benefit relationship. If there is not
      yet sufficient benefit to be gained from the study to offset the risks to which
      participants were exposed and it is expected that important scientific
      information would be obtained if the trial were continued, early termination
      constitutes an unethical alteration of the risk-benefit relationship. This
      violates the grounds on which permission is given to conduct human research,
      patients consent to participate, and investigators agree to conduct studies.
      These knowable and avoidable changes in risk-benefit relationship should
      generally be seen as impermissible.

PMID- 15994363
TI  - Building on relationships of trust in biobank research.
AB  - Trust among current and future patients is essential for the success of biobank
      research. The submission of an informed consent is an act of trust by a patient
      or a research subject, but a strict application of the rule of informed consent
      may not be sensitive to the multiplicity of patient interests at stake, and could
      thus be detrimental to trust. According to a recently proposed law on "genetic
      integrity" in Sweden, third parties will be prohibited from requesting or seeking
      genetic information about an individual. Cumbersome restrictions on research may
      be lifted, thus creating a more favourable climate for medical research.

PMID- 15994364
TI  - What is the role of the research ethics committee? Paternalism, inducements, and
      harm in research ethics.
AB  - In a recent paper Edwards, Kirchin, and Huxtable have argued that research ethics
      committees (RECs) are often wrongfully paternalistic in their approach to medical
      research. They argue that it should be left to competent potential research
      subjects to make judgments about the acceptability of harms and benefits relating
      to research, and that this is not a legitimate role for any REC. They allow an
      exception to their overall antipaternalism, however, in that they think RECs
      should have the power to prohibit the use of financial inducements to recruit
      research subjects into trials. In this paper it is argued that these claims are
      unjustified and implausible. A sketch is provided of an alternative model of the
      role of the REC as an expert body making judgments about the acceptability of
      research proposals through a consensual weighing of different moral
      considerations.

PMID- 15994365
TI  - Autonomy, consent, and limiting healthcare costs.
AB  - While protection of autonomy is crucial to the practice of medicine, there is the
      persistent risk of a disconnect between the notion of self-determination and the
      need for a socially responsible medical system. An example of unbridled autonomy
      is the preferential use of costly medications without an appreciation of the
      impact of using these more expensive drugs on the resource pool of others. In the
      USA, costly medications of questionable incremental benefit are frequently
      prescribed with the complicity of both doctors and patients. Limiting self
      determination in medication choices via an appreciation of the principle of
      justice reaches a better moral balance, while at the same time acknowledging the
      goals of doing good and avoiding harm in patient care.

PMID- 15994366
TI  - Whose information is it anyway? Informing a 12-year-old patient of her terminal
      prognosis.
AB  - OBJECTIVE: To examine students' attitudes and potential behaviour towards
      informing a 12-year-old patient of her terminal prognosis in a situation in which
      her parents do not wish her to be told, as they pass through a modern medical
      curriculum. DESIGN: A cohort study of students entering Glasgow University's new
      medical curriculum in October 1996. METHODS: Students' responses obtained before
      year 1 and at the end of years 1, 3, and 5 to the "childhood leukaemia" vignette
      of the Ethics in Health Care Survey Instrument (EHCI) were examined
      quantitatively and qualitatively. Analysis of the students' multichoice answers
      enabled measurement of the movement towards professional consensus opinion. An
      analysis of their written justifications for their answers helped to determine
      whether their reasoning was consistent with professional consensus and enabled
      measurement of changes in knowledge content and recognition of the values
      inherent in the vignette. Themes on the students' reasoning behind their decision
      to tell the patient or not were also identified. RESULTS: Unlike other vignettes
      of the EHCI in which autonomy was a main theme, few students chose the consensus
      answer before year 1 and there was no significant movement towards consensus at
      any point during the course. In defence of their decision to withhold
      information, the students expressed strong paternalistic opinions. The patient's
      age was seen as a barrier to respecting her autonomy. CONCLUSIONS: It is
      important to identify students' perceptions on entry to medical school.
      Transformative learning theory may provide the basis for an approach to foster
      doctors who consider the rights of young people. Small-group teaching is most
      conducive to this approach. The importance of positive role modelling is also
      emphasised.

PMID- 15994367
TI  - Estrogen increases mitochondrial efficiency and reduces oxidative stress in
      cerebral blood vessels.
AB  - We report here that estrogen (E(2)) modulates mitochondrial function in the
      vasculature. Mitochondrial dysfunction is implicated in the etiology of vascular
      disease; thus, vasoprotection by estrogen may involve hormonal effects on the
      mitochondria. To test this hypothesis, mitochondria were isolated from cerebral
      blood vessels obtained from ovariectomized female rats, with or without E(2)
      replacement. Estrogen receptor-alpha (ER-alpha) was detected in mitochondria by
      immunoblot and confocal imaging of intact vessels. E(2) treatment in vivo
      increased the levels of specific proteins in cerebrovascular mitochondria, such
      as ER-alpha, cytochrome c, subunit IV of complex IV, and manganese superoxide
      dismutase, all encoded in the nuclear genome, and subunit I of complex IV,
      encoded in the mitochondrial genome. Levels of glutathione peroxidase-1 and
      catalase, however, were not affected. Functional assays of mitochondrial citrate
      synthase and complex IV, key rate-limiting steps in energy production, showed
      that E(2) treatment increased enzyme activity. In contrast, mitochondrial
      production of hydrogen peroxide was decreased in vessels from E(2)-treated
      animals. In vitro incubation of cerebral vessels with 10 nM 17beta-estradiol for
      18 h also elevated levels of mitochondrial cytochrome c. This effect was blocked
      by the estrogen receptor antagonist fulvestrant (ICI-182,780, Faslodex) but was
      unaffected by inhibitors of nitric-oxide synthase or phosphoinositide-3-kinase.
      Nuclear respiratory factor-1 protein, a primary regulator of nuclear gene-encoded
      mitochondrial genes, was significantly increased by long-term estrogen treatment
      in vivo. In summary, these novel findings suggest that vascular protection by
      E(2) is mediated, in part, by modulation of mitochondrial function, resulting in
      greater energy-producing capacity and decreased reactive oxygen species
      production.

PMID- 15994368
TI  - N-methyl-N'-nitro-N-nitrosoguanidine activates cell-cycle arrest through distinct
      mechanisms activated in a dose-dependent manner.
AB  - S(N)1-alkylating agents, such as the mutagenic and cytotoxic drug N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG), robustly activate the DNA damage-responsive G(2)
      checkpoint. Establishment of this checkpoint is dependent on a functional
      mismatch repair (MMR) system; however, exposure to high doses of MNNG overrides
      the requirement for MMR to trigger G(2) arrest. In addition, unlike moderate-dose
      exposure, in which the G(2) checkpoint is attenuated in ataxia-telangiectasia,
      mutated (ATM)-deficient cells, high-dose MNNG treatment activates G(2) arrest
      through an ATM-independent mechanism. We document that this arrest is sensitive
      to the pharmacological agents caffeine and 7-hydroxystaurosporine (UCN-01) that
      inhibit the checkpoint kinases ATM/ATM and Rad-3-related (ATR) and Chk1/Chk2,
      respectively. Furthermore, these agents block inactivation of the cell-cycle
      regulatory molecules Cdc25C and Cdc2, establishing the downstream mechanism
      through which high-dose MNNG establishes G(2) arrest. Activation of both Chk2 and
      Chk1 was independent of ATM and MMR in response to high-dose MNNG, unlike the
      response to moderate doses of this drug. Chk2 was found to be dispensable for
      cell-cycle arrest in response to high-dose MNNG treatment; however, ATR
      deficiency and decreased Chk1 expression forced by RNA interference resulted in
      diminished checkpoint response. These results indicate that MNNG activates the
      G(2) checkpoint through different mechanisms activated in a dose-dependent
      fashion.

PMID- 15994369
TI  - Development of simplified vasoactive intestinal peptide analogs with receptor
      selectivity and stability for human vasoactive intestinal peptide/pituitary
      adenylate cyclase-activating polypeptide receptors.
AB  - Vasoactive intestinal peptide (VIP) is a widespread neurotransmitter whose
      physiological and pathophysiological actions are mediated by two receptor
      classes, VIP/pituitary adenylate cyclase-activating polypeptide (VPAC) 1 and
      VPAC2. VIP is a 28-amino acid peptide that is rapidly degraded and simplified;
      metabolically stable analogs are needed. In this study, we use information from
      studies of the VIP pharmacophore for VPAC1/VPAC2 to design nine simplified VIP
      analogs that could have high affinity and selectivity for each VPAC or that
      retained high affinity for both VPACs and were metabolically stable. From binding
      studies of their abilities to directly interact with hVPAC1 (T47D cells, hVPAC1
      transfected cells) and hVPAC2 (Sup T1- and VPAC2-transfected cells) and to
      stimulate adenylate cyclase in each, two analogs
      [(Ala(2,8,9,11,19,22,24,25,27,28))VIP and (Ala(2,8,9,11,19,24-28))VIP] were found
      to have >2000- and >600-fold selectivity for hVPAC1. None of the nine analogs had
      hVPAC2 selectivity. However, two simplified analogs [(Ala(2,8,9,16,19,24))VIP and
      (Ala(2,8,9,16,19,24,25))VIP] retained high affinity and potency for both hVPACs.
      125I-[Ala(2,8,9,16,19,24,25)]VIP was much more metabolically stable than 125I
      VIP. The availability of these simplified analogs of VIP, which are metabolically
      stable and have either hVPAC1 selectivity or retain high affinity for both
      hVPACs, should be useful for exploring the role of VPAC subtypes in mediating
      VIPs' actions as well as being useful therapeutically and for exploring the
      usefulness of VIP receptor imaging of tumors and VIP receptor-mediated tumor
      cytotoxicity.

PMID- 15994370
TI  - Vascular binding, blood flow, transporter, and enzyme interactions on the
      processing of digoxin in rat liver.
AB  - The roles of vascular binding, flow, transporters, and enzymes as determinants of
      the clearance of digoxin were examined in the rat liver. Digoxin is metabolized
      by Cyp3a and utilizes the organic anion transporting polypeptide 2 (Oatp2) and P
      glycoprotein (Pgp) for influx and excretion, respectively. Uptake of digoxin was
      found to be similar among rat periportal (PP) and perivenous (PV) hepatocytes
      isolated by the digitonin-collagenase method. The Km values for uptake were 180
      +/- 112 and 390 +/- 406 nM, Vmax values were 13 +/- 8 and 18 +/- 4.9 pmol/min/mg
      protein, and nonsaturable components were 9.2 +/- 1.3 and 10.7 +/- 2.5
      microl/min/mg for PP and PV, respectively. The evenness of distribution of Oatp2
      and Pgp was confirmed by Western blotting and confocal immunofluorescent
      microscopy. When digoxin was recirculated to the rat liver preparation in Krebs
      Henseleit bicarbonate (KHB) for 3 h in absence or presence of 1% bovine serum
      albumin (BSA) and 20% red blood cell (rbc) at flow rates of 40 and 10 ml/min,
      respectively, biexponential decays were observed. Fitted results based on
      compartmental analyses revealed a higher clearance (0.244 +/- 0.082 ml/min/g) for
      KHB-perfused livers over the rbc-albumin-perfused livers (0.114 +/- 0.057
      ml/min/g) (P < 0.05). We further found that binding of digoxin to 1% BSA was
      modest (unbound fraction = 0.64), whereas binding to rbc was associated with slow
      on (0.468 +/- 0.021 min(-1)) and off (1.81 +/- 0.12 min(-1)) rate constants. We
      then used a zonal, physiologically based pharmacokinetic model to show that the
      difference in digoxin clearance was attributed to binding to BSA and rbc and not
      to the difference in flow rate and that clearance was unaffected by transporter
      or enzyme heterogeneity.

PMID- 15994371
TI  - Route-dependent effect of nutritional support on liver glucose uptake.
AB  - The liver is a major site of glucose disposal during chronic (5 day) total
      parenteral (TPN) and enteral (TEN) nutrition. Net hepatic glucose uptake (NHGU)
      is dependent on the route of delivery when only glucose is delivered acutely;
      however, the hepatic response to chronic TPN and TEN is very similar. We aimed to
      determine whether the route of nutrient delivery altered the acute (first 8 h)
      response of the liver and whether chronic enteral delivery of glucose alone could
      augment the adaptive response to TPN. Chronically catheterized conscious dogs
      received either TPN or TEN containing glucose, Intralipid, and Travasol for
      either 8 h or 5 days. Another group received TPN for 5 days, but approximately
      50% of the glucose in the nutrition was given via the enteral route (TPN+EG).
      Hepatic metabolism was assessed with tracer and arteriovenous difference
      techniques. In the presence of similar arterial plasma glucose levels
      (approximately 6 mM), NHGU and net hepatic lactate release increased
      approximately twofold between 8 h and 5 days in TPN and TEN. NHGU (26 +/- 1 vs.
      23 +/- 3 micromol.kg(-1).min(-1)) and net hepatic lactate release (44 +/- 1 vs.
      34 +/- 6 micromol.kg(-1).min(-1)) in TPN+EG were similar to results for TPN,
      despite lower insulin levels (96 +/- 6 vs. 58 +/- 16 pM, TPN vs. TPN+EG). TEN
      does not acutely enhance NHGU or disposition above that seen with TPN. However,
      partial delivery of enteral glucose is effective in decreasing the insulin
      requirement during chronic TPN.

PMID- 15994372
TI  - Gene expression profiling of the long-term adaptive response to hypoxia in the
      gills of adult zebrafish.
AB  - Low oxygen levels (hypoxia) play a role in clinical conditions such as stroke,
      chronic ischemia, and cancer. To better understand these diseases, it is crucial
      to study the responses of vertebrates to hypoxia. Among vertebrates, some
      teleosts have developed the ability to adapt to extremely low oxygen levels. We
      have studied long-term adaptive responses to hypoxia in adult zebrafish. We used
      zebrafish that survived severe hypoxic conditions for 3 wk and showed adaptive
      behavioral and phenotypic changes. We used cDNA microarrays to investigate
      hypoxia-induced changes in expression of 15,532 genes in the respiratory organs
      (the gills). We have identified 367 differentially expressed genes of which 117
      showed hypoxia-induced and 250 hypoxia-reduced expressions. Metabolic depression
      was indicated by repression of genes in the TCA cycle in the electron transport
      chain and of genes involved in protein biosynthesis. We observed enhanced
      expression of the monocarboxylate transporter and of the oxygen transporter
      myoglobin. The hypoxia-induced group further included the genes for Niemann-Pick
      C disease and for Wolman disease [lysosomal acid lipase (LAL)]. Both diseases
      lead to a similar intra- and extracellular accumulation of cholesterol and
      glycolipids. The Niemann-Pick C protein binds to cholesterol from internal
      lysosomal membranes and is involved in cholesterol trafficking. LAL is
      responsible for lysosomal cholesterol degradation. Our data suggest a novel
      adaptive mechanism to hypoxia, the induction of genes for lysosomal lipid
      trafficking and degradation. Studying physiological responses to hypoxia in
      species tolerant for extremely low oxygen levels can help identify novel
      regulatory genes, which may have important clinical implications.

PMID- 15994373
TI  - Sexually dimorphic micturition in rats: relationship of perineal muscle activity
      to voiding pattern.
AB  - In the present study we examined the possibility that striated muscle activity
      may underlie sexually dimorphic micturition in rats. Micturition dynamics, the
      gross anatomy of the external urethral sphincter, and the participation of the
      striated perineal muscles in micturition were compared in urethane-anesthetized
      adult male and female rats. Bladder contraction characteristics, particularly the
      magnitude of bladder high-frequency pressure waves during voiding, differed
      between sexes. Dissections indicated that the sphincter was more extensive and
      thicker in males than in females. Electromyography showed that in both sexes the
      sphincter discharged in bursts that correlated with the rising phase of high
      frequency bladder pressure oscillations. Regional differences in discharge
      pattern were seen in the sphincters of males, with the proximal part of the
      sphincter showing components activated during bladder filling. Bulbospongiosus,
      ischiocavernosus, and cremaster muscles also were activated during bladder
      contraction in males. In both sexes transection of the motor branch of the
      lumbosacral plexus eliminated the bladder high-frequency oscillations and reduced
      voided volume. Neurectomy did not affect bladder pressure but reduced voiding
      efficiency by 45% in males. In females the bladder pressure was dramatically
      decreased, but voiding efficiency only decreased by 24%. Our findings suggest
      that, in rats, striated perineal muscles contribute to the sexually dimorphic
      micturition. Activity of the dimorphic perineal muscles may regulate genital and
      urinary urethra expulsive functions, helping to expel seminal plug and fluids
      through the long urethra in the male.

PMID- 15994374
TI  - Antagonism of corticotropin-releasing hormone alters serotonergic-induced changes
      in brain temperature, but not sleep, of rats.
AB  - Serotonin is involved in many physiological processes, including the regulation
      of sleep and body temperature. Administration into rats of low doses (25, 50
      mg/kg) of the 5-HT precursor l-5-hydroxytryptophan (5-HTP) at the beginning of
      the dark period of the 12:12-h light-dark cycle initially increases wakefulness.
      Higher doses (75, 100 mg/kg) increase nonrapid eye movement (NREM) sleep. The
      initial enhancement of wakefulness after low-dose 5-HTP administration may be a
      direct action of 5-HT in brain or due to 5-HT-induced activation of other arousal
      promoting systems. One candidate arousal-promoting system is corticotropin
      releasing hormone (CRH) and the hypothalamic-pituitary-adrenal axis. Serotonergic
      activation by 5-HTP at the beginning of the dark period also induces hypothermia.
      Because sleep and body temperature are influenced by circadian factors, one aim
      of this study was to determine responses to 5-HTP when administered at a
      different circadian time, the beginning of the light period. Results obtained
      show that all doses of 5-HTP (25-100 mg/kg) administered at light onset initially
      increase wakefulness; NREM sleep increases only after a long delay, during the
      subsequent dark period. Serotonergic activation by 5-HTP at light onset induces
      hypothermia, the time course of which is biphasic after higher doses (75, 100
      mg/kg). Intracerebroventricular pretreatment with the CRH receptor antagonist
      alpha-helical CRH does not alter the impact of 5-HTP on sleep-wake behavior but
      potentiates the hypothermic response to 50 mg/kg 5-HTP. These data suggest that
      serotonergic activation by peripheral administration of 5-HTP may modulate sleep
      wake behavior by mechanisms in addition to direct actions in brain and that
      circadian systems are important determinants of the impact of serotonergic
      activation on sleep and body temperature.

PMID- 15994375
TI  - NHE3 in an ancestral vertebrate: primary sequence, distribution, localization,
      and function in gills.
AB  - In mammals, the Na+/H+ exchanger 3 (NHE3) is expressed with Na+/K+-ATPase in
      renal proximal tubules, where it secretes H+ and absorbs Na+ to maintain blood pH
      and volume. In elasmobranchs (sharks, skates, and stingrays), the gills are the
      dominant site of pH and osmoregulation. This study was conducted to determine
      whether epithelial NHE homologs exist in elasmobranchs and, if so, to localize
      their expression in gills and determine whether their expression is altered by
      environmental salinity or hypercapnia. Degenerate primers and RT-PCR were used to
      deduce partial sequences of mammalian NHE2 and NHE3 homologs from the gills of
      the euryhaline Atlantic stingray (Dasyatis sabina). Real-time PCR was then used
      to demonstrate that mRNA expression of the NHE3 homolog increased when stingrays
      were transferred to low salinities but not during hypercapnia. Expression of the
      NHE2 homolog did not change with either treatment. Rapid amplification of cDNA
      was then used to deduce the complete sequence of a putative NHE3. The 2,744-base
      pair cDNA includes a coding region for a 2,511-amino acid protein that is 70%
      identical to human NHE3 (SLC9A3). Antisera generated against the carboxyl tail of
      the putative stingray NHE3 labeled the apical membranes of Na+/K+-ATPase-rich
      epithelial cells, and acclimation to freshwater caused a redistribution of
      labeling in the gills. This study provides the first NHE3 cloned from an
      elasmobranch and is the first to demonstrate an increase in gill NHE3 expression
      during acclimation to low salinities, suggesting that NHE3 can absorb Na+ from
      ion-poor environments.

PMID- 15994376
TI  - Understanding the infrared spectrum of bare CH5+.
AB  - Protonated methane, CH5+, continues to elude definitive structural assignment, as
      large-amplitude vibrations and hydrogen scrambling challenge both theory and
      experiment. Here, the infrared spectrum of bare CH5+ is presented, as detected by
      reaction with carbon dioxide gas after resonant excitation by the free electron
      laser at the FELIX facility in the Netherlands. Comparison of the experimental
      spectrum at approximately 110 kelvin to finite-temperature infrared spectra,
      calculated by ab initio molecular dynamics, supports fluxionality of bare CH5+
      under experimental conditions and provides a dynamical mechanism for exchange of
      hydrogens between CH3 tripod positions and the three-center bonded H2 moiety,
      which eventually leads to full hydrogen scrambling. The possibility of
      artificially freezing out scrambling and internal rotation in the simulations
      allowed assignment of the infrared spectrum despite this pronounced fluxionality.

PMID- 15994377
TI  - Premelting at defects within bulk colloidal crystals.
AB  - Premelting is the localized loss of crystalline order at surfaces and defects at
      temperatures below the bulk melting transition. It can be thought of as the
      nucleation of the melting process. Premelting has been observed at the surfaces
      of crystals but not within. We report observations of premelting at grain
      boundaries and dislocations within bulk colloidal crystals using real-time video
      microscopy. The crystals are equilibrium close-packed, three-dimensional
      colloidal structures made from thermally responsive microgel spheres. Particle
      tracking reveals increased disorder in crystalline regions bordering defects, the
      amount of which depends on the type of defect, distance from the defect, and
      particle volume fraction. Our observations suggest that interfacial free energy
      is the crucial parameter for premelting in colloidal and atomic-scale crystals.

PMID- 15994378
TI  - Structure of a synaptic gammadelta resolvase tetramer covalently linked to two
      cleaved DNAs.
AB  - The structure of a synaptic intermediate of the site-specific recombinase
      gammadelta resolvase covalently linked through Ser10 to two cleaved duplex DNAs
      has been determined at 3.4 angstrom resolution. This resolvase, activated for
      recombination by mutations, forms a tetramer whose structure is substantially
      changed from that of a presynaptic complex between dimeric resolvase and the
      cleavage site DNA. Because the two cleaved DNA duplexes that are to be recombined
      lie on opposite sides of the core tetramer, large movements of both protein and
      DNA are required to achieve strand exchange. The two dimers linked to the DNAs
      that are to be recombined are held together by a flat interface. This may allow a
      180 degrees rotation of one dimer relative to the other in order to reposition
      the DNA duplexes for strand exchange.

PMID- 15994379
TI  - Supernova olivine from cometary dust.
AB  - An interplanetary dust particle contains a submicrometer crystalline silicate
      aggregate of probable supernova origin. The grain has a pronounced enrichment in
      18O/16O (13 times the solar value) and depletions in 17O/16O (one-third solar)
      and 29Si/28Si (<0.8 times solar), indicative of formation from a type II
      supernova. The aggregate contains olivine (forsterite 83) grains <100 nanometers
      in size, with microstructures that are consistent with minimal thermal
      alteration. This unusually iron-rich olivine grain could have formed by
      equilibrium condensation from cooling supernova ejecta if several different
      nucleosynthetic zones mixed in the proper proportions. The supernova grain is
      also partially encased in nitrogen-15-rich organic matter that likely formed in a
      presolar cold molecular cloud.

PMID- 15994380
TI  - Coming together: the ATS/ERS consensus on clinical pulmonary function testing.

PMID- 15994381
TI  - Identifying asthma in population studies: from single entity to a multi-component
      approach.

PMID- 15994382
TI  - Bronchodilator reversibility in COPD: the roguish but harmless little brother of
      airway hyperresponsiveness?

PMID- 15994383
TI  - Non-CF bronchiectasis: does knowing the aetiology lead to changes in management?
AB  - The aim of the current study was to review the aetiology of non-cystic fibrosis
      (CF) bronchiectasis from two tertiary paediatric respiratory units in order to
      determine how often making a specific aetiological diagnosis leads to a change in
      management, and to assess the contribution of computed tomography (CT) in
      determining the underlying diagnosis. The case records of all patients who were
      diagnosed as having bronchiectasis by CT, currently being seen at the Royal
      Brompton Hospital and Great Ormond Street Hospital for Children (London, UK),
      were reviewed. All patients had undergone extensive investigations, and the
      underlying aetiology and the area of pulmonary involvement (as seen on CT) were
      recorded. A total of 136 patients were identified; there were 65 young males and
      the group median (range) age was 12.1 yrs (3.1-18.1). Immunodeficiency,
      aspiration and primary ciliary dyskinesia accounted for 67% of the cases. In 77
      (56%) children, the identification of a cause led to a specific change in
      management. There was no association between aetiology and the distribution of CT
      abnormalities. In conclusion, immunodeficiency and other intrinsic abnormalities
      account for the majority of cases of non-cystic fibrosis bronchiectasis seen in
      the current authors' units. Computed tomography scans do not contribute towards
      identifying the aetiology and, most importantly, a specific aetiological
      diagnosis frequently leads to a change in management.

PMID- 15994384
TI  - Nerve growth factor is released by IL-1beta and induces hyperresponsiveness of
      the human isolated bronchus.
AB  - Nerve growth factor (NGF) is a neurotrophic factor essential for the development
      and survival of neurons, and is also an important mediator of inflammation. It is
      released by airway cells stimulated by interleukin (IL)-1beta. As IL-1beta
      induces airway hyperresponsiveness (AHR) to the tachykinin NK-1 receptor agonist
      [Sar9,Met(O2)11]-substance P in human isolated bronchi, the aim of this study was
      to determine whether IL-1beta was able to induce NGF release from isolated
      bronchi, and whether NGF might participate into IL-1beta-induced AHR. IL-1beta
      (10 ng x mL(-1); 21 degrees C; 15 h) increased the release of NGF from human
      isolated bronchi in vitro, and, in organ bath studies, the response of human
      bronchi to [Sar9,Met(O2)11]-substance P (0.1 microm). A significant correlation
      was found between these responses. AHR induced by IL-1beta was abolished by a
      blocking anti-human NGF antibody. Finally, NGF (1 ng x mL(-1); 37 degrees C; 0.5
      h) by itself induced a significant increase in [Sar9,Met(O2)11]-substance P
      responsiveness. By contrast, it did not change the maximal contraction to
      acetylcholine. In conclusion, the present study clearly demonstrated that nerve
      growth factor may participate in the airway hyperresponsiveness induced by
      interleukin-1beta, which supports the neuro-immune cross-talk that may be active
      in the development of hyperresponsiveness in the human airways, and suggests
      nerve growth factor is active in the airways in asthma.

PMID- 15994385
TI  - Modulation of airway inflammation and resistance in mice by a nicotinic receptor
      agonist.
AB  - Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have anti
      inflammatory properties and in some instances smooth muscle relaxing effects.
      Since inflammation and airway smooth muscle contraction are two major components
      of asthma, the present authors investigated the effects of DMPP on airway
      inflammation and airway resistance in a mouse model of asthma. Mice were
      sensitised and challenged with ovalbumin (OVA) and treated either
      intraperitoneally or intranasally with DMPP. The effect of DMPP was tested on
      airway inflammation, airway resistance and on the increase of intracellular
      calcium in bronchial smooth muscle cells. DMPP given either during sensitisation,
      OVA challenges or throughout the protocol prevented lung inflammation and
      decreased the serum level of OVA specific immunoglobulin E. DMPP administration
      reduced the number of total cells, lymphocytes and eosinophils in the
      bronchoalveolar lavage (BAL) fluid. Intranasal DMPP administration was as
      effective as dexamethasone (DEXA) in reducing total cell count and eosinophil
      counts in BAL fluid. DMPP, but not DEXA, reduced tissue inflammation. Intranasal
      DMPP, given 10 min before the test, reduced airway responsiveness to metacholine.
      DMPP also reduced the increase in intracellular calcium in response to
      bradykinin. In conclusion, these results show that 1,1-dimethyl-4
      phenylpiperazinium reduces lung inflammation and prevents airway
      hyperresponsiveness in the mouse model of asthma.

PMID- 15994386
TI  - Operational definitions of asthma in studies on its aetiology.
AB  - The most popular way to define asthma based on questionnaires is to use
      definitions taken from cross-sectional international studies on asthma. These
      definitions may not, however, be optimal for future studies focusing on risk
      factors of asthma. The current authors, therefore, compared the performance of
      different operational definitions of asthma. The European Community Respiratory
      Health Study I was a cross-sectional study of 21,924 subjects aged between 25-44
      yrs in 18 countries. Operational definitions of asthma compared included
      different combinations of symptoms of asthma and bronchial hyperresponsiveness. A
      continuous asthma score, ranging from 0-8, was defined as the sum of positive
      answers to eight main symptom questions. There was no threshold in the
      associations of asthma symptoms with severity or risk factors of asthma, which
      would have suggested a dichotomous definition of asthma. Using dichotomous
      definitions requiring the presence of several asthma symptoms strengthened
      associations with studied risk factors, and also increased the estimated
      specificity and positive predictive value. Using a continuous asthma score also
      improved the power of the analyses. In conclusion, dichotomous definitions of
      asthma yielding higher odds ratios are achieved by requiring positive responses
      to several questions on symptoms. However, symptoms of asthma are possibly best
      analysed as a continuous asthma score.

PMID- 15994387
TI  - Traditional and patient-centred outcomes with three classes of asthma medication.
AB  - Lung function is commonly used as the primary endpoint in asthma clinical trials,
      but it may not reflect changes which are important to patients. The present study
      compared changes in, and relationships between, traditional and patient-centred
      end-points during treatment with three classes of asthma medication. Subjects
      with mild-to-moderate asthma were randomised to double-blind, double-dummy
      crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d.,
      then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules,
      with 6-week treatment periods and 1-week washouts. Individual "traditional" end
      points (symptoms, reliever use, forced expiratory volume in one second per cent
      predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient
      centred" end-points (asthma control questionnaire, quality of life, patient
      global assessments) were assessed. Principal component analysis and linear
      modelling were used to explore overall rank orders for treatment, and
      relationships between outcomes. A total of 58 subjects were randomised. The rank
      order of benefit from eformoterol and fluticasone differed for three factors
      derived from principal component analysis (eformoterol>fluticasone for
      symptom/reliever use factor, fluticasone>eformoterol for lung function factor,
      eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third
      for all three factors. A significant relationship between patient-based variables
      and lung function was found only for montelukast treatment. In asthma treatment,
      traditional end-points do not fully capture patient-centred benefits, and the
      relationship between end-points differs with medication class.

PMID- 15994388
TI  - Bronchodilator response in the lung health study over 11 yrs.
AB  - Long-term changes in bronchodilator response in people with mild chronic
      obstructive pulmonary disease were assessed in this study. Changes in forced
      expiratory volume in one second (FEV1) in response to isoproterenol was measured
      in 4,194 participants in the Lung Health Study annually for 5 yrs, and again 11
      yrs after study entry. Responses were quantitated in terms of mL (absolute), as
      per cent of the pre-bronchodilator value (relative), and as a per cent of the
      predicted normal value (% predicted). At baseline, the mean pre-bronchodilator
      FEV1 was 75.4% predicted, and responses were small. Relative and percentage
      predicted responses were similar in males and females; and correlated positively
      with methacholine reactivity, and negatively with smoking intensity and age.
      Baseline bronchodilator responses did not correlate with subsequent decline in
      FEV1. There was a substantial increase in response over the first year of the
      study, largely due to smoking cessation, with larger increases in those who
      stopped smoking. After the first year absolute responses changed little in those
      who maintained smoking cessation, but increased in those who did not. Mean
      relative and percentage predicted responses increased in all participants
      throughout the study. There was substantial annual variability of absolute
      response, and it was poorly reproducible in individual participants. In
      conclusion, smoking cessation increased bronchodilator response, and response did
      not predict the rate of decline of forced expiratory volume in one second.

PMID- 15994389
TI  - Exhaled nitric oxide from lung periphery is increased in COPD.
AB  - Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the
      sources of NO. The present study measured eNO at multiple expired flows (MEFeNO)
      to partition NO into alveolar (Calv,NO) and bronchial (Jaw,NO) fractions to
      investigate peripheral lung contribution to eNO in chronic obstructive lung
      disease (COPD). MEFeNO were made in 81 subjects including 18 nonsmokers, 16
      smokers and 47 COPD patients of different severity by the classification of the
      Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n = 14), 1 (n =
      7), 2 (n = 11), 3 (n = 8) and 4 (n = 7). COPD severity was correlated with an
      increased Calv,NO regardless of the patient's smoking habit or current treatment.
      The levels of Calv,NO (in ppb) were 1.4+/-0.09 in nonsmokers, 2.1+/-0.1 in
      smokers categorised as GOLD stage 0 (smokers-GOLD0), 3.3+/-0.18 in GOLD1-2 and
      3.4+/-0.1 in GOLD3-4. Jaw,NO levels (pL x s(-1)) were higher in nonsmokers than
      smokers-GOLD0 (716.2+/-33.3 versus 464.7+/-41.8), GOLD3-4 (609.4+/-71). Diffusion
      of NO in the airways (Daw,NO pL x ppb(-1) s(-1)) was higher (p<0.05) in GOLD3-4
      than in nonsmokers (15+/-1.2 versus 11+/-0.5) and smokers-GOLD0 (11.6+/-0.5).
      MEFeNO measurements were reproducible, free from day-to-day and diurnal variation
      and were not affected by bronchodilators. In conclusion, chronic obstructive
      pulmonary disease is associated with elevated alveolar nitric oxide. Measurements
      of nitric oxide at multiple expired flows may be useful in monitoring
      inflammation and progression of chronic obstructive pulmonary disease, and the
      response to anti-inflammatory treatment.

PMID- 15994390
TI  - Decreased macrophage release of TGF-beta and TIMP-1 in chronic obstructive
      pulmonary disease.
AB  - The present study tested the hypothesis that alveolar macrophages (AM) from
      patients with chronic obstructive pulmonary disease (COPD) release more pro
      inflammatory and/or less anti-inflammatory mediators than those from smokers with
      normal lung function and never-smokers. AM were sorted by flow cytometry from
      bronchoalveolar lavage fluid in 13 patients with COPD (mean+/-SEM 67+/-2 yrs,
      forced expiratory volume in one second (FEV1) 61+/-4% reference), 16 smokers with
      normal lung function (55+/-2 yrs, FEV1 97+/-4% reference) and seven never-smokers
      (67+/-7 yrs, FEV1 94+/-4% reference). After sorting, AM were cultured (with and
      without lipopolysaccharide stimulation) after 4 h and 24 h, and the
      concentrations of leukotriene B4 (LTB4), transforming growth factor (TGF)-beta1
      and tissue inhibitor of metalloproteinase (TIMP)-1 were quantified in the
      supernatant by ELISA. The production of reactive oxygen intermediates (ROI) in
      freshly isolated AM was determined by flow cytometry. LTB4 secretion and ROI
      production were not different between groups. In contrast, AM from COPD patients
      released significantly less TGF-beta1 and TIMP-1 than those from smokers with
      normal lung function and nonsmokers. In conclusion, these observations are
      compatible with reduced anti-inflammatory and anti-elastolytic capacity in
      chronic obstructive pulmonary disease, which is likely to contribute to the
      pathogenesis of the disease.

PMID- 15994391
TI  - The protease inhibitor PI*S allele and COPD: a meta-analysis.
AB  - In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common
      than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary
      disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of
      COPD due to the PI*S allele is not clear. The current authors located studies
      that addressed the risk of COPD or measured lung function in individuals with the
      PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was
      performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI
      SZ compound heterozygotes compared with PI MM (normal) individuals was
      significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17
      cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes
      was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD
      risk after correcting for smoking. Furthermore, mean forced expiratory volume in
      one second, a measure of airflow obstruction and a defining feature of COPD, did
      not differ between PI MS and PI MM individuals. There were not enough cases to
      summarise the risk of COPD in PI SS homozygotes. In conclusion, the results show
      that the PI SZ genotype is a significant risk factor for chronic obstructive
      pulmonary disease. The risk of chronic obstructive pulmonary disease due to the
      PI MS genotype is not substantially elevated.

PMID- 15994392
TI  - Characterisation of natural killer cells and CD56+ T-cells in sarcoidosis
      patients.
AB  - The aim of the current study was to investigate the frequency, phenotype and
      functional activity of natural killer (NK) cells and CD56+ T-cells in the
      bronchoalveolar lavage fluid and peripheral blood of patients with pulmonary
      sarcoidosis when compared with healthy volunteers, using staining with a panel of
      monoclonal antibodies followed by flow cytometry. The results revealed that the
      majority of the lung NK cell subpopulation expressed CD56(bright). In contrast,
      there was a predominant CD56(dim) subset in the blood of both patients and
      healthy controls. Most lung NK cells expressed C-type lectin-like human leukocyte
      antigen (HLA)-E-specific inhibitory receptor (i.e. CD94/NKG2A), but only a few
      lung NK cells expressed killer cell immunoglobulin-like inhibitory receptors
      specific for HLA-A, -B or -C molecules. In addition, a significantly increased
      number of CD56+ T-cells were observed in the blood of patients when compared with
      controls. Upon in vitro stimulation, both lung NK and CD56+ T-cells produced
      considerable amounts of interferon-gamma and tumour necrosis factor-alpha. Thus,
      in the lungs of patients with pulmonary sarcoidosis, a distinct phenotype of
      natural killer cells with the capacity to produce cytokines and actively
      participate in the T-helper 1-like inflammatory response associated with
      sarcoidosis was identified.

PMID- 15994393
TI  - Quality control of equipment in home mechanical ventilation: a European survey.
AB  - Quality control of the equipment used in home mechanical ventilation is necessary
      in order to ensure that patients safely and accurately receive the prescribed
      ventilatory support. The aim of this study was to carry out a survey on the
      quality-control procedures in different centres and countries. The survey was
      carried out in the context of a European Commission Concerted Action covering 16
      European countries. The study was extensive and detailed, involving 326 centres,
      which provided home ventilation to >20,000 patients. The survey showed that: 1)
      ventilator servicing was mainly carried out by external companies (62% of
      centres), with a servicing frequency ranging 3-12 months; 2) interaction between
      servicing companies and prescribers was limited (only 61% of centres were always
      informed of major incidents); 3) participation of centres in equipment quality
      control was poor (only 56% of centres assessed that patients/caregivers correctly
      cleaned/maintained the ventilator); and 4) centres were insufficiently aware of
      vigilance systems (only 23% of centres). Moreover, the data showed considerable
      inter- and intra-country differences. The size of the centre was an important
      determinant of many of these quality-control aspects. This survey provides
      information that will enable the European Commission Concerted Action to
      formulate recommendations on procedures for home-ventilator quality control.

PMID- 15994394
TI  - Improvement in Cheyne-Stokes respiration following cardiac resynchronisation
      therapy.
AB  - The effect of standard cardiac resynchronisation therapy (CRT) on the severity of
      Cheyne-Stokes respiration (CSR) in patients with congestive heart failure was
      studied. It was hypothesised that CRT, through its known beneficial effects on
      cardiac function, would stabilise the control of breathing and reduce CSR. Twenty
      eight patients who were eligible for CRT and receiving optimised medical
      treatment for congestive heart failure were referred for overnight
      polysomnography, including monitoring of thoracic and abdominal movements to
      identify CSR and obstructive sleep apnoea events. Patients underwent repeat
      polysomnography after 6 months of CRT to re-evaluate sleep quality and sleep
      disordered breathing. Twelve of the 28 patients had significant CSR (43%); 10
      patients had a successful implantation and underwent repeat polysomnography a
      mean+/-SD 27+/-7 weeks after continuous biventricular pacing. Six of the 10
      patients experienced a significant decrease in CSR severity following CRT,
      associated with correction of congestive heart failure-related hyperventilation
      and hypocapnia. Circulation time, oxygen saturation, frequency of obstructive
      apnoeas and sleep quality did not change. In conclusion, cardiac
      resynchronisation therapy is associated with a reduction in Cheyne-Stokes
      respiration, which may contribute to improved clinical outcome in patients
      treated with cardiac resynchronisation therapy.

PMID- 15994395
TI  - VEGF levels in the alveolar compartment do not distinguish between ARDS and
      hydrostatic pulmonary oedema.
AB  - Although overexpression of vascular endothelial growth factor (VEGF) 165 in the
      lung causes pulmonary oedema, its role in human acute lung injury (ALI) is
      unclear. VEGF levels are reported to be lower in bronchoalveolar lavage from ALI
      patients compared with normals, but these studies did not include a comparably
      ill control group with noninflammatory pulmonary oedema. The current authors
      hypothesised that VEGF levels in pulmonary oedema fluid would be lower in ALI
      patients compared with control patients with severe hydrostatic pulmonary oedema.
      VEGF was measured in pulmonary oedema fluid and plasma from 56 patients with ALI
      and 46 controls with severe hydrostatic pulmonary oedema. Pulmonary oedema fluid
      levels of VEGF did not differ between patients with hydrostatic oedema (median
      799 pg x mL(-1), interquartile range (IQR) 226-2,281) and ALI (median 507, IQR
      0.8-1,031). Plasma levels were also the same (median 20.5 pg x mL(-1), IQR 0-152
      versus 4.8, IQR 0-99.8). There was no association between plasma or oedema fluid
      VEGF levels and outcomes including mortality. Vascular endothelial growth factor
      levels in pulmonary oedema fluid were depressed both in acute lung injury and
      hydrostatic pulmonary oedema. The decrease in air space concentrations of
      vascular endothelial growth factor in acute lung injury may not be a function of
      the degree of lung injury, but rather may result from alveolar flooding.

PMID- 15994396
TI  - Early gastrostomy reduces the rate of ventilator-associated pneumonia in stroke
      or head injury patients.
AB  - Presence of a nasogastric tube is a risk factor for the development of ventilator
      associated pneumonia (VAP). Alternatively, gastrostomy can be used for
      administration of enteral feedings. To determine whether early performance of
      gastrostomy affects frequency of VAP, a randomised, controlled study was carried
      out in patients mechanically ventilated for stroke or head injury. In the
      gastrostomy group, patients underwent the procedure within 24 h of intubation. A
      nasogastric tube was inserted in controls. Individual subjects were studied for 3
      weeks. In total, 20 subjects (mean age 48+/-15.2 yrs) were allocated to the
      gastrostomy group, and 21 to the control group (46.6+/-15.4 yrs). Of these
      groups, two (10%) and eight (38.1%) developed VAP, respectively. Four patients
      with gastrostomy and three controls did not complete the study (due to weaning
      from ventilatory support or death). After excluding these subjects, difference in
      VAP frequency persisted: two out of 16 subjects with gastrostomy had VAP (12.5%)
      versus eight out of 18 controls (44.4%). There were no differences in duration of
      hospitalisation or mortality between the two groups. In conclusion, in patients
      mechanically ventilated for stroke or head injury early gastrostomy is associated
      with a lower frequency of ventilator-associated pneumonia compared with a
      nasogastric tube.

PMID- 15994397
TI  - Effect of ventilation strategy and surfactant on inflammation in experimental
      pneumonia.
AB  - This study explored, the inflammatory response during experimental pneumonia in
      surfactant-depleted animals as a function of ventilation strategies and
      surfactant treatment. Following intratracheal instillation of Group B
      streptococci (GBS), surfactant-depleted piglets were treated with conventional
      (positive-end expiratory pressure (PEEP) of 5 cmH2O, tidal volume 7 mL x kg(-1))
      or open lung ventilation. During the latter, collapsed alveoli were recruited by
      applying high peak inspiratory pressures for a short period of time, combined
      with high levels of PEEP and the smallest possible pressure amplitude. Subgroups
      in both ventilation arms also received exogenous surfactant. Conventionally
      ventilated healthy animals receiving GBS and surfactant-depleted animals
      receiving saline served as controls. In contrast with both control groups,
      surfactant-depleted animals challenged with GBS and conventional ventilation
      showed high levels of interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and
      myeloperoxidase in bronchoalveolar lavage fluid after 5 h of ventilation. Open
      lung ventilation attenuated this inflammatory response, but exogenous surfactant
      did not. Systemic dissemination of the inflammatory response was minimal, as
      indicated by low serum levels of IL-8 and TNF-alpha. In conclusion, the current
      study indicates that the ventilation strategy, but not exogenous surfactant, is
      an important modulator of the inflammation during Group B streptococci pneumonia
      in mechanically ventilated surfactant-depleted animals.

PMID- 15994398
TI  - Pulmonary manifestations of multicentric Castleman's disease in HIV infection: a
      clinical, biological and radiological study.
AB  - The aim of the present study was to report clinical, radiological and
      bronchoalveolar lavage (BAL) findings in patients with pulmonary manifestations
      of HIV-associated multicentric Castleman's disease (MCD). This was a
      retrospective study of 12 patients with histologically proven MCD. Clinical
      manifestations were as follows: dyspnoea (nine out of 12 cases), cough (n = 10),
      bilateral crackles (n = 10), together with high fever, malaise, peripheral
      lymphadenopathy (n = 12), and hepatosplenomegaly (n = 10). Two patients developed
      acute respiratory distress syndrome. Chest radiographs and computed tomography
      scans showed reticular (n = 7) and/or nodular (n = 7) interstitial patterns, with
      mediastinal lymphadenopathy (n = 9), and bilateral pleural effusion (n = 3).
      Fibreoptic endoscopy was normal in all cases. BAL analysis showed
      hypercellularity (n = 6) and/or lymphocytosis (n = 6), and human herpesvirus-8
      DNA was detected in two out of two cases. Specific stains and cultures for
      pathogens were negative. All patients received etoposide and/or vinblastine, and
      improved after 2-4 days. Relapses were frequent (50 attacks in 12 patients). Six
      patients developed a non-Hodgkin's lymphoma, and five died. In conclusion, the
      pulmonary manifestation of HIV-related multicentric Castleman's disease is an
      acute reticulo-nodular interstitial pneumonitis, associated with severe systemic
      symptoms and peripheral lymphadenopathy. In bronchoalveolar lavage fluid,
      cellularity is not specific and human herpesvirus-8 DNA is detected. The clinical
      course is specific due to a rapid onset and regression, frequent relapses and a
      high occurrence of non-Hodgkin's lymphoma.

PMID- 15994399
TI  - Tuberculosis infection in children who are contacts of immigrant tuberculosis
      patients.
AB  - The present study aimed to determine what proportion of children who are in close
      contact with immigrant tuberculosis (TB) patients are infected with Mycobacterium
      tuberculosis. For 1.5 yrs, 14 municipal health services in The Netherlands
      collected data from all non-Dutch TB patients and their contacts. Close contacts
      aged < 16 yrs received a tuberculin skin test (TST). A positive TST was defined
      as an induration of > or = 10 mm among nonvaccinated children, and > or = 16 mm
      among bacille Calmette-Guerin-vaccinated children. In total, 244 patients had 359
      close contacts aged < 16 yrs. Nine out of the 359 (2.5%) had TB. A TST test was
      given to 298 out of the 359 (83%). Of the 115 contacts of 44 extrapulmonary TB
      patients, three (3%) had a positive TST. Of the 186 contacts of 58 positive
      pulmonary TB patients, 30 (16%) had a positive TST. Contacts of sputum smear
      positive patients significantly more often had a positive TST (25%), compared
      with the contacts of sputum smear-negative patients (7%). Children born abroad
      significantly more often had a positive TST (20%) than children born in The
      Netherlands (5%). In conclusion, the prevalence of active tuberculosis and latent
      tuberculosis infection among children who are close contacts of immigrant
      tuberculosis patients is high and warrants an expansion of contact investigation.

PMID- 15994400
TI  - Airflow limitation and changes in pulmonary function among bleachery workers.
AB  - This study investigated whether chronic airflow limitation and rapid decline in
      pulmonary function were associated with peak exposures to ozone and other
      irritant gases in pulp mills. Bleachery workers potentially exposed to irritant
      gassings (n = 178) from three Swedish pulp mills, and a comparison group of
      workers not exposed to irritant gassings (n = 54) from two paper mills, were
      studied. Baseline surveys occurred in 1995-1996, with follow-up surveys in 1998
      1999. Participants performed spirometry and answered questions regarding ozone,
      chlorine dioxide (ClO2), and sulphur dioxide (SO2) gassings. From regression
      models controlling for potential confounders, declines in both the forced
      expiratory volume in one second (FEV1) (-24 mL x yr(-1)) and the forced vital
      capacity (FVC) (-19 mL x yr(-1)) were associated with ClO2/SO2 gassings. At
      follow-up, the prevalence of chronic airflow limitation (i.e. FEV1/FVC less than
      the lower limit of normal) was elevated for participants with only pre-baseline
      ozone gassings and with both pre-baseline and interval ozone gassings, after
      controlling for potential confounders. These findings suggest that obstructive
      effects among bleachery workers are associated with ozone gassings, and that
      adverse effects on spirometry might also accompany chlorine dioxide/sulphur
      dioxide gassings. Peak exposures to irritant gases in pulp mills should be
      prevented.

PMID- 15994401
TI  - Computed tomographic imaging of the airways: relationship to structure and
      function.
AB  - Alterations in the structure of the airways, collectively termed airway
      remodelling, contribute to airflow obstruction in a variety of chronic lung
      diseases. While histology has provided valuable insights into the structure of
      airway wall remodelling, this technique is invasive and does not allow the
      longitudinal analysis of airway wall dimensions. Technical advances in computed
      tomography allow the assessment of airway wall dimensions, and are ideally suited
      for the noninvasive investigation of the pathogenesis of airway wall remodelling
      and the evaluation of new therapeutic interventions. The aim of this article is
      to review the use of computed tomography in the investigation of airway structure
      and function in health and disease.

PMID- 15994402
TI  - General considerations for lung function testing.

PMID- 15994403
TI  - The dream of a vaccine against tuberculosis; new vaccines improving or replacing
      BCG?
AB  - In the last 10 yrs, work with experimental laboratory models has developed many
      new vaccine candidates against tuberculosis (TB). They include subunit vaccines,
      modified bacilli Calmette-Guerin (BCG) and attenuated Mycobacterium tuberculosis.
      Phase I clinical trials of new TB vaccine candidates have begun for the first
      time after 80 yrs of use of BCG. Many of these new trials involve recombinant BCG
      or improve BCG immunity by boosting with vaccines consisting of subunits or
      attenuated vaccinia virus expressing TB antigens. However, effective vaccination
      against TB presents diverse and complex challenges. For example, TB infection can
      become reactivated years later and infection does not guarantee resistance to a
      subsequent second infection. A truly effective TB vaccine may, therefore, have to
      elicit an immune response that is greater than that induced by natural infection.
      In addition, various different populations have to be protected including those
      vaccinated with BCG and those infected with M. tuberculosis or HIV. The goal is a
      new generation of vaccines effective against respiratory forms of tuberculosis.
      As a first step, good candidate vaccines able to boost bacille Calmette-Guerin
      and thereby improve protection could be a reality in the near future.
      Tuberculosis vaccine candidates, able to replace the currently used bacille
      Calmette-Guerin and/or make the eradication of tuberculosis feasible, can only be
      expected in the long-term, and safe live vaccines could be promising candidates.

PMID- 15994404
TI  - The use of iloprost in early pregnancy in patients with pulmonary arterial
      hypertension.
AB  - In patients with pulmonary hypertension, pregnancy is associated with a high risk
      of maternal death. Such patients are counselled to avoid pregnancy, or if it
      occurs, are offered early interruption. Some patients, however, decide to
      continue with their pregnancy and others may present with symptoms for the first
      time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option
      for these high-risk patients. The present study describes three patients with
      pulmonary arterial hypertension of various aetiologies who were treated with the
      prostacyclin analogue iloprost during pregnancy, and the post-partum period.
      Nebulised iloprost commenced as early as 8 weeks of gestation and patients were
      admitted to hospital between 24-36 weeks of gestation. All pregnancies were
      completed with a duration of between 25-36 weeks and all deliveries were by
      caesarean section under local anaesthetic. All patients delivered children free
      from congenital abnormalities, and there was no post-partum maternal or infant
      mortality. In conclusion, although pregnancy is strongly advised against in those
      with pulmonary hypertension, the current authors have achieved a successful
      outcome for mother and foetus with a multidisciplinary approach and targeted
      pulmonary vascular therapy.

PMID- 15994405
TI  - Hoarseness, cough and cervical lymphadenopathy.

PMID- 15994406
TI  - Antibody deficiency in bronchiectasis.

PMID- 15994407
TI  - Early noninvasive ventilation failure in COPD with acute on chronic respiratory
      failure.

PMID- 15994408
TI  - Combination therapy with bosentan and phosphodiesterase-5 inhibitor in pulmonary
      arterial hypertension.

PMID- 15994409
TI  - Efficacy of fluticasone on cough.

PMID- 15994410
TI  - EUS: confusion about terminology and its consequences.

PMID- 15994412
TI  - Toll-like receptor 4 mediates mitochondrial DNA damage and biogenic responses
      after heat-inactivated E. coli.
AB  - An important site of cellular damage in bacterial sepsis is mitochondrial DNA
      (mtDNA), which we proposed is caused by reactive oxygen and nitrogen species
      generated by activation of signaling through specific toll-like receptors (TLR).
      In wild-type (Wt) mice injected with heat-inactivated E. coli, hepatic TLR4 and
      TLR2 proteins were up-regulated with TLR-dependent increases in transcript levels
      for tumor necrosis factor (TNF-alpha), interleukin 6, nitric oxide synthase-II
      (iNOS), and NADPH oxidase 2 (Nox2). The accompanying stress significantly
      depleted hepatic mtDNA despite eight- and fourfold increases in manganese
      superoxide dismutase (MnSOD) and mitochondrial transcription factor A (Tfam)
      expression, respectively. The identical E. coli dose generated significantly less
      TNF-alpha, NO, and Nox2 in TLR4-/- and TLR2/4-/- but not in TLR2-/- mice. TLR4-/-
      and TLR2/4-/- compared with Wt mice were protected from mtDNA oxidation but
      showed no Tfam up-regulation and little copy number restoration. A critical role
      in the mtDNA damage was determined for TLR4-mediated iNOS transcription through
      the MyD88 pathway. In Wt mice, mtDNA depletion was avoided by selective iNOS
      blockade, and residual mtDNA loss was linked to NF-kappaB-dependent TNF-alpha
      expression. These data disclose the dual role of TLR4 in mtDNA damage and
      compensatory mitochondrial biogenic responses after innate immune activation.

PMID- 15994413
TI  - A dynamic alpha-beta inter-subunit agonist signaling complex is a novel feedback
      mechanism for regulating L-type Ca2+ channel opening.
AB  - L-type Ca2+ channels are macromolecular protein complexes in neurons and myocytes
      that open in response to cell membrane depolarization to supply Ca2+ for
      regulating gene transcription and vesicle secretion and triggering cell
      contraction. L-type Ca2+ channels include a pore-forming alpha and an auxiliary
      beta subunit, and alpha subunit openings are regulated by cellular Ca2+ through a
      mechanism involving the Ca2+-sensing protein calmodulin (CaM) and CaM binding
      motifs in the alpha subunit cytoplasmic C terminus. Here we show that these CaM
      binding motifs are "auto-agonists" that increase alpha subunit openings by
      binding the beta subunit. The CaM binding domains are necessary and sufficient
      for the alpha subunit C terminus to bind the beta subunit in vitro, and excess
      CaM blocks this interaction. Addition of CaM binding domains to native cardiac L
      type Ca2+ channels in excised cell membrane patches increases openings, and this
      agonist effect is prevented by excess CaM. Recombinant LTCC openings are also
      increased by exogenous CaM binding domains by a mechanism requiring the beta
      subunit, and excess CaM blocks this effect. Thus, the bifunctional ability of the
      alpha subunit CaM binding motifs to competitively associate with the beta subunit
      or CaM provides a novel paradigm for feedback control of cellular Ca2+ entry.

PMID- 15994414
TI  - Identification of microsatellite DNA markers for the giant anteater Myrmecophaga
      tridactyla.
AB  - The giant anteater (Myrmecophaga tridactyla) is found from Belize and Guatemala
      to Paraguay and Argentina. Its conservation status is considered vulnerable by
      IUCN. Here we report the isolation and characterization of six microsatellite
      loci. Positive loci for (GT)(n) were isolated using a magnetic bead hybridization
      selection protocol. The number of alleles per locus as well as the heterozygosity
      and PCR conditions are described. These loci will be useful for studying
      population structure, genetic diversity, and paternity in M. tridactyla wild
      populations.

PMID- 15994415
TI  - Inferences on the role of insertion in a mutation accumulation experiment with
      Drosophila melanogaster using RAPDs.
AB  - The genetic variability for RAPDs band pattern was studied in a set of 157
      mutation accumulation (MA) lines of Drosophila melanogaster. These MA lines were
      derived from the same isogenic base population and subsequently maintained by
      full-sib mating during 132 generations. The ancestral pattern of the original
      isogenic base can be unambiguously established as the consensus pattern of the MA
      lines and, because these lines are expected to be homozygous, dominance for band
      pattern is not a concern. Only repeatable changes in band pattern were
      considered. The number of ancestral bands detected implies that nine-nucleotide
      targets are enough for repeatable PCR amplification. Compared with the ancestral
      pattern, one MA line lost one band and two MA lines gained a new one. These
      results can be accounted for by the insertion of transposable elements occurring
      at a rate 0.07 < i < 0.21 per whole haploid genome and generation. This range is
      typical for Drosophila and consistent with the previously observed mobility for
      the roo family, supporting the generality of previous estimates of spontaneous
      mutation rates for morphological and fitness traits based on these MA lines. The
      sequence of one of the new bands suggests that the Idefix family is also active
      in the lines.

PMID- 15994416
TI  - Mutant allele frequencies in domestic cat populations in Arkansas and Tennessee.
AB  - We conducted surveys of mutant allele frequencies of four cat populations in
      Arkansas and Tennessee during 2002. Our calculations and analyses support that
      Southwestern cat populations were relatively more genetically similar to each
      other than compared to cat populations in other areas of North America. However,
      the cat population of Fort Smith is slightly different from the other cat
      populations studied in the Southwestern United States. Although there is a clear
      significant spatial geographic pattern for many mutant coat allele frequencies in
      the United States and Canada cat populations (d, l, S, and W), our results
      revealed that there is not a significant isolation-by-distance model affecting
      these cat populations. Our data also support the historical migration hypothesis
      because our calculated allele frequencies were genetically similar to cat
      populations located in ancestral areas of Europe. Different phenograms, including
      new European cat genetic profiles, showed that the Southwestern cat populations
      studied are of a clear British origin. Therefore, migration routes of early
      Arkansas and Tennessee settlers help explain the similarities of allele
      frequencies among domestic cat populations.

PMID- 15994417
TI  - Mutational bias in penguin microsatellite DNA.
AB  - Analysis of nucleotide sequence variation at a microsatellite DNA locus revealed
      extensive size homoplasy of alleles in Adelie penguins (Pygoscelis adeliae).
      Variation in the flanking regions at this locus allowed discrimination between
      mechanisms proposed for length changes in microsatellite DNA alleles. We further
      examined the structure of alleles for the same microsatellite DNA locus across 11
      additional species of penguin (Spheniscidae) by mapping allele sequences onto an
      independent penguin phylogeny. Our analysis indicated that the repeat motifs
      appear to have evolved independently on several occasions. We observed sequence
      instability in the region bordering the repeat tract with a transversional bias
      predominating. We propose that this bias results from inaccurate DNA replication
      owing to the sequence context of this repeat tract. Because we show that regions
      flanking repeat sequences exhibit this mutational bias, this cautions against the
      use of such regions for phylogeny reconstruction.

PMID- 15994418
TI  - Establishment of a cell line derived from a canine prostate carcinoma with a
      highly rearranged karyotype.
AB  - Akin to the situation in humans, dogs are frequently affected by tumors of the
      prostate. The malignancies share many similarities between both species, for
      example, median age at the onset of the disease and metastatic behavior. In human
      prostatic tumor samples, investigations of prepared metaphase spreads showed a
      variety of chromosomal aberrations, with trisomies of chromosomes 7, 8, and 17 as
      the leading cytogenetic abnormalities. In this article we present one case of a
      canine adenocarcinoma of the prostate, including clinical examination and
      establishment of a cell line from a tumor sample obtained from the affected 10
      year-old male Briard. Searching for similarities between both species in respect
      to chromosomal changes within the tumor samples, we investigated prepared
      metaphases of the canine cell line cytogenetically. These investigations
      presented a highly rearranged karyotype showing a large biarmed marker consisting
      of material from chromosomes 1 and 2 in addition to centromeric fusions between
      dog chromosomes 1 and 5 that both could be identified in every metaphase
      investigated, while centric fusions of chromosomes 4 and 5 occurred in up to 50%
      of the metaphases. The cell line grew very well and showed evidence of being
      spontaneously immortalized when it crossed the 20th passage.

PMID- 15994419
TI  - Melanic moth frequencies in Yorkshire, an old English industrial hot spot.
AB  - A survey has been carried out in Leeds, England, in the west Yorkshire industrial
      heartland, and in neighboring York, surrounded by agriculture, of melanic
      frequency in the moth species Biston betularia, Odontoptera bidentata, and Apamea
      crenata. All show a decline in melanics in the postindustrial environment, the
      first over almost the full range from nearly 100% to less that 10%, the others to
      smaller extents. Changes in several species over as great a magnitude and as wide
      an area must result from selection. The results are compared with others along a
      transect through northern England. The onset of response is progressively later
      from west to east. The rate of decline is lower at the extremes of the transect
      to west and east than it is in the center. We still do not have a clear picture
      of the causes of the changes. One major factor is likely to be selective
      predation, which is shown to be critically dependent on predation rate. As a
      consequence, differences in settling behavior between the species could account
      for different responses even if the species are attacked by the same predators.

PMID- 15994420
TI  - Genome sizes in afrotheria, xenarthra, euarchontoglires, and laurasiatheria.
AB  - Topical literature and Web site databases provide genome sizes for approximately
      4,000 animal species, invertebrates and vertebrates, 330 of which are mammals. We
      provide the genome size for 67 mammalian species, including 51 never reported
      before. Knowledge of genome size facilitates sequencing projects. The data
      presented here encompassed 5 Metatheria (order Didelphimorphia) and 62 Eutheria:
      15 Xenarthra, 24 Euarchontoglires (Rodentia), as well as 23 Laurasiatheria (22
      Chiroptera and 1 species from Perissodactyla). Already available karyotypes
      supplement the haploid nuclear DNA contents of the respective species. Thus, we
      established the first comprehensive set of genome size measurements for 15
      Xenarthra species (armadillos) and for 12 house-mouse species; each group was
      previously represented by only one species. The Xenarthra exhibited much larger
      genomes than the modal 3 pg DNA known for mammals. Within the genus Mus, genome
      sizes varied between 2.98 pg and 3.68 pg. The 22 bat species we measured support
      the low 2.63 pg modal value for Chiroptera. In general, the genomes of
      Euarchontoglires and Laurasiatheria were found being smaller than those of
      (Afrotheria and) Xenarthra. Interspecific variation in genome sizes is discussed
      with particular attention to repetitive elements, which probably promoted the
      adaptation of extant mammals to their environment.

PMID- 15994421
TI  - Population genetics of wood-feeding cockroaches in the genus Cryptocercus.
AB  - Members of the genus Cryptocercus are xylophagous, wingless, subsocial
      cockroaches that inhabit decaying logs in temperate forests. Given their
      winglessness, subsocial living, and the patchy distribution of food resources
      (decomposing logs), it is likely that Cryptocercus populations are substructured.
      Allozyme variation at eight polymorphic loci was assayed for 10 subpopulations of
      Cryptocercus darwini and 13 subpopulations of Cryptocercus wrighti, both of which
      are distributed in the Appalachian Mountains. The mean F(IS) was 0.13 and F(ST)
      was about 0.25 for both C. darwini and C. wrighti. The relatedness among
      individuals of a subpopulation of both species was not significantly different
      from that expected among full sibs. In terms of how genetic variation is
      partitioned, C. darwini and C. wrighti differed from each other substantially.
      Most of the genetic variation occurred among subpopulations of C. wrighti in the
      same region and among subpopulations of C. darwini in different regions. We
      discuss the factors that may have contributed to the observed similarities and
      differences in the breeding structure of the two species.

PMID- 15994422
TI  - Discovery of SNPs in soybean genotypes frequently used as the parents of mapping
      populations in the United States and Korea.
AB  - Single nucleotide polymorphisms (SNPs) including insertion/deletions (indels)
      serve as useful and informative genetic markers. The availability of high
      throughput and inexpensive SNP typing systems has increased interest in the
      development of SNP markers. After fragments of genes were amplified with primers
      derived from 110 soybean GenBank ESTs, sequencing data of PCR products from 15
      soybean genotypes from Korea and the United States were analyzed by SeqScape
      software to find SNPs. Among 35 gene fragments with at least one SNP among the 15
      genotypes, SNPs occurred at a frequency of 1 per 2,038 bp in 16,302 bp of coding
      sequence and 1 per 191 bp in 16,960 bp of noncoding regions. This corresponds to
      a nucleotide diversity (theta) of 0.00017 and 0.00186, respectively. Of the 97
      SNPs discovered, 78 or 80.4% were present in the six North American soybean
      mapping parents. The addition of "Hwaeomputkong," which originated from Japan,
      increased the number to 92, or 94.8% of the total number of SNPs present among
      the 15 genotypes. Thus, Hwaeomputkong and the six North American mapping parents
      provide a diverse set of soybean genotypes that can be successfully used for SNP
      discovery in coding DNA and closely associated introns and untranslated regions.

PMID- 15994423
TI  - Federal legislation to limit bulk drug exports.

PMID- 15994424
TI  - Corticotropin-releasing factor receptor 1 mediates acute and delayed stress
      induced visceral hyperalgesia in maternally separated Long-Evans rats.
AB  - In rodents, maternal pup interactions play an important role in programming the
      stress responsiveness of the adult organism. The aims of this study were 1) to
      determine the effect of different neonatal rearing conditions on acute and
      delayed stress-induced visceral sensitivity as well as on other measures of
      stress sensitivity of the adult animal; and 2) to determine the role of
      corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF(1)R) in mediating
      visceral hypersensitivity. Three groups of male Long-Evans rat pups were used:
      separation from their dam for 180 min daily from postnatal days 2-14 (MS180),
      daily separation (handling) for 15 min (H), or no handling. The visceromotor
      responses (VMR) to colorectal distension, stress-induced colonic motility, and
      anxiety-like behavior were assessed in the adult rats. The VMR was assessed at
      baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h
      poststress. Astressin B, a nonselective CRF-R antagonist, or CP-154,526, a
      selective CRF(1)R antagonist, was administered before the stressor and/or before
      the 24-h measurement. MS rats developed acute and delayed stress-induced visceral
      hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no
      change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited
      enhanced stress-induced colonic motility and increased anxiety-like behavior. In
      MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR.
      Rearing conditions have a significant effect on adult stress responsiveness
      including immediate and delayed visceral pain responses to an acute stressor.
      Both acute and delayed stress-induced visceral hypersensitivity in MS rats are
      mediated by the CRF/CRF(1)R system.

PMID- 15994425
TI  - Nitric oxide inhibits cAMP-dependent CFTR trafficking in intestinal epithelial
      cells.
AB  - Nitric oxide is produced during intestinal inflammation and inhibits the
      epithelial responsiveness to cAMP-dependent secretagogues. The effect is
      presumably due to inhibition of activation of the CFTR. However, because
      insertion of CFTR into the epithelial apical membrane is also a cAMP-dependent
      process, we tested the hypothesis that NO could inhibit cAMP-dependent CFTR
      trafficking. SCBN intestinal epithelial cells were treated with forskolin to
      activate adenylate cyclase activity. The cells were fixed at various times and
      immunostained for CFTR. Some cells were pretreated with the nitric oxide donor
      PAPA-NONOate, the protein kinase A inhibitor H89, or the microtubule blocker
      nocodazole. Cross sections of epithelial monolayers were then studied under
      fluorescence, and the ratio of apical to basolateral CFTR immunoreactivity was
      determined. Stimulation of adenylate cyclase activity caused an increase in the
      apical-to-basolateral ratio of CFTR within 30 s. This effect was transient and
      preceded changes in short-circuit current in SCBN monolayers mounted in Ussing
      chambers. PAPA-NONOate, H89, and nocodazole all reduced forskolin-stimulated CFTR
      trafficking. The inhibitory effect of the NO donor was not affected by
      pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one. PAPA-NONOate reduced forskolin-stimulated increases in
      intracellular cAMP. The data suggest that a portion of the inhibitory effect of
      nitric oxide donors on cAMP-dependent chloride secretion is through the
      inhibition of cAMP-dependent insertion of CFTR into the apical plasma membrane.
      These data provide insight into the mechanism of secretory dysfunction in
      inflammatory diseases of the gut where mucosal nitric oxide is elevated.

PMID- 15994426
TI  - NH2-terminal signals in ATP7B Cu-ATPase mediate its Cu-dependent anterograde
      traffic in polarized hepatic cells.
AB  - Cu is an essential cofactor of cellular proteins but is toxic in its free state.
      The hepatic Cu-ATPase ATP7B has two functions in Cu homeostasis: it loads Cu+
      onto newly synthesized apoceruloplasmin in the secretory pathway, thereby
      activating the plasma protein; and it participates in the excretion of excess Cu+
      into the bile. To carry out these two functions, the membrane protein responds to
      changes in intracellular Cu levels by cycling between the Golgi and apical
      region. We used polarized hepatic WIF-B cells and high-resolution confocal
      microscopy to map the itinerary of endogenous and exogenous ATP7B under different
      Cu conditions. In Cu-depleted cells, ATP7B resided in a post-trans-Golgi network
      compartment that also contained syntaxin 6, whereas in Cu-loaded cells, the
      protein relocated to unique vesicles very near to the apical plasma membrane as
      well as the membrane itself. To determine the role of ATP7B's cytoplasmic NH2
      terminus in regulating its intracellular movements, we generated seven
      mutations/deletions in this large [approximately 650 amino acid (AA)] domain and
      analyzed the Cu-dependent behavior of the mutant ATP7B proteins in WIF-B cells.
      Truncation of the ATP7B NH2 terminus up to the fifth copper-binding domain (CBD5)
      yielded an active ATPase that was insensitive to cellular Cu levels and
      constitutively trafficked to the opposite (basolateral) plasma membrane domain.
      Fusion of the NH2-terminal 63 AA of ATP7B to the truncated protein restored both
      its Cu responsiveness and correct intracellular targeting. These results indicate
      that important targeting information is contained in this relatively short
      sequence, which is absent from the related CuATPase, ATP7A.

PMID- 15994427
TI  - Generation of hypochlorite-modified proteins by neutrophils during ischemia
      reperfusion injury in rat liver: attenuation by ischemic preconditioning.
AB  - Although it is well documented that neutrophils are critical for the delayed
      phase of hepatic ischemia-reperfusion injury, there is no direct evidence for a
      specific neutrophil-derived oxidant stress in vivo. Therefore, we used a model of
      60 min of partial hepatic ischemia and 0-24 h of reperfusion to investigate
      neutrophil accumulation and to analyze biomarkers for a general oxidant stress
      [glutathione disulfide (GSSG) and malondialdehyde (MDA)] and for a neutrophil
      specific oxidant stress [hypochlorite (HOCl)-modified epitopes] in rats. Plasma
      alanine transaminase activities and histology showed progressively increasing
      liver injury during reperfusion, when hepatic GSSG and soluble MDA levels were
      elevated. At that time, few neutrophils were present in sinusoids. However, the
      number of hepatocytes positively stained for HOCl-modified epitopes increased
      from 6 to 24 h of reperfusion, which correlated with the bulk of hepatic
      neutrophil accumulation and extravasation into the parenchyma. Consistent with a
      higher oxidant stress at later times, hepatic GSSG and protein-bound MDA levels
      further increased. Treatment with the NADPH oxidase inhibitor diphenyleneiodonium
      chloride attenuated postischemic oxidant stress (GSSG, protein-bound MDA, and
      hepatocytes positively stained for HOCl-modified epitopes) and liver injury at 24
      h of reperfusion. Ischemic preconditioning suppressed all oxidant stress
      biomarkers, liver injury, and extravasation of neutrophils. In conclusion,
      extravasated neutrophils generate HOCl, which diffuses into hepatocytes and
      causes oxidative modifications of intracellular proteins during the neutrophil
      mediated reperfusion injury phase. Ischemic preconditioning is an effective
      intervention for reduction of the overall inflammatory response and, in
      particular, for limitation of the cytotoxic activity of neutrophils during the
      later reperfusion period.

PMID- 15994428
TI  - Transforming growth factor-beta1 drives airway remodeling in cigarette smoke
      exposed tracheal explants.
AB  - Small airway remodeling (SAR) is an important cause of airflow obstruction in
      cigarette smokers, but whether SAR represents a response to smoke-evoked
      inflammation or is directly mediated by smoke-induced growth factor production is
      disputed. To examine this process, we exposed rat tracheal explants, a model free
      of exogenous inflammatory cells, to cigarette smoke in vitro. Cigarette smoke
      caused release of active transforming growth factor (TGF)-beta1, and this was
      prevented by the oxidant scavenger tetramethythiourea. Nuclear immunostaining for
      phospho-Smad2, a TGF-beta downstream signaling molecule, was present in
      epithelial and interstitial cells within 1 h after exposure. Smoke caused
      upregulation of gene expression of connective tissue growth factor (CTGF), a
      mediator of TGF-beta fibrogenic effects, within 2 h, and upregulation of
      procollagen gene expression at 24 h; both changes could be prevented by the TGF
      beta antagonist fetuin (alpha2-HS-glycoprotein). In a cell-free system,
      recombinant human TGF-beta latency-associated peptide was oxidized by cigarette
      smoke, and smoke released active TGF-beta1 from recombinant latent TGF-beta1 via
      an oxidant mechanism. These experiments suggest that SAR in cigarette smokers may
      be caused by direct, smoke-mediated, oxidant-driven induction of growth factor
      signaling in the airway wall, and that SAR does not necessarily require exogenous
      inflammatory cells.

PMID- 15994429
TI  - Interferon-gamma-Jak-Stat signaling in pulmonary lymphangioleiomyomatosis and
      renal angiomyolipoma: a potential therapeutic target.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML) are
      proliferative lesions that occur in sporadic patients, and at much higher
      frequency in patients with tuberous sclerosis (TSC). The TSC1 and TSC2 genes play
      a critical role in their pathogenesis. Here we report a marked decrease in
      interferon (IFN)-gamma expression in both sporadic and TSC-associated AML and
      LAM. A marked increase in Stat1 expression and phosphorylation at Ser 727, and in
      phospho-Tyr705-Stat3 levels, was also seen in both AML and LAM tissues. Our
      results demonstrate that the IFN-gamma-Jak-Stat pathway is perturbed in TSC
      related and sporadic LAM and AML, and suggest that IFN-gamma has potential
      therapeutic benefit for treatment of those lesions.

PMID- 15994430
TI  - Concordance of genotypes in pre- and post-lung transplantation DNA samples.
AB  - Genetic epidemiology studies of end-stage lung disease are potentially hindered
      by low numbers of participants due to early death of patients from the underlying
      disease, or due to exclusion from studies after patients have had lung
      transplants, because of concern about bias of genotype data due to chimerism. The
      number of participants enrolled in genetic studies of end-stage lung disease
      could be increased by including those individuals who have undergone lung
      transplant. We hypothesized that individuals who have had lung transplants can be
      included in genetic epidemiology studies that use single nucleotide polymorphism
      and short tandem repeat marker data, without confounding due to chimerism. Ten
      probands with severe, early-onset chronic obstructive pulmonary disease were
      included in this analysis. Pre- and post-lung transplant DNA samples were used in
      the investigation of concordance of genotype results for 12 short tandem repeat
      markers and 23 single nucleotide polymorphisms. Concordance was observed for all
      genotypes before and after lung transplant. We conclude that the risk of biasing
      genetic epidemiology studies due to donor lung-related DNA microchimerism is low,
      and that the inclusion of post-lung transplantation participants will allow for
      larger genetic epidemiology studies of individuals with end-stage lung disease.

PMID- 15994431
TI  - Antibodies to the polymeric immunoglobulin receptor with different binding and
      trafficking patterns.
AB  - The polymeric immunoglobulin receptor (pIgR) has been proposed as a therapeutic
      target, but its potential depends on the efficiency of uptake and trafficking of
      the receptor ligand. Mouse monoclonal antibodies (Mabs) directed against pIgR,
      selected for strong binding to secretory component (SC) and secretory IgA (sIgA),
      were tested in a transcytosis assay in 16HBEo--cells (human bronchial epithelial
      cell line) transfected with human pIgR. Intracellular trafficking was followed by
      confocal microscopy. Mabs fell into two classes. For two Mabs, transcytosis from
      basolateral to apical surface is rapid, unidirectional, and little Mab is
      retained in the cell. For three Mabs, basolateral to apical transcytosis occurs
      to a significantly lesser extent, reverse transcytosis is permitted, and some of
      the Mab is retained in the perinuclear region even after 24 h. When tested for
      their ability to recognize and immunoprecipitate pIgR with systematic truncations
      and deletions of the five immunoglobulin (Ig)-like domains, all Mabs bound to the
      fifth Ig-like domain, but three of them also bound to the C-terminal region of
      pIgR near the plasma membrane. Different binding sites probably account for the
      different trafficking of these Mabs and may predict differential therapeutic
      utility.

PMID- 15994432
TI  - Cytokine-induced endothelial arginase expression is dependent on epidermal growth
      factor receptor.
AB  - L-arginine is metabolized to nitric oxide (NO) by NO synthase (NOS), or to urea
      and L-ornithine by arginase. L-ornithine contributes to vascular remodeling in
      pulmonary hypertension via metabolism to polyamines and proline. Previously we
      found that cytokines upregulate both NOS and arginase in pulmonary arterial
      endothelial cells. We hypothesized that cytokine-induced arginase I and II
      expression depend on epidermal growth factor (EGF) receptor (EGFR) activity.
      Bovine pulmonary arterial endothelial cells were treated with lipopolysaccharide
      and tumor necrosis factor-alpha (L/T). L/T treatment resulted in a substantial
      increase in urea production, and this increase in urea production was potently
      inhibited by both genistein and AG1478, inhibitors of EGFR. Levels of arginase I
      protein and arginase II mRNA were increased in response to L/T treatment, and
      genistein prevented the L/T-induced elevations in both arginase I protein and
      arginase II mRNA levels. L/T treatment increased production of nitrites and
      inducible NOS mRNA accumulation, and genistein and AG1478 had little effect on
      these changes. EGF (50 ng/ml) treatment resulted in enhanced urea production.
      Finally, a 170-kD protein was phosphorylated upon treatment with either EGF or
      L/T. Our results indicate that arginase induction by L/T depends in part on EGFR
      activity. We speculate that EGFR inhibitors may attenuate vascular remodeling
      without affecting NO release, and thus may represent novel therapeutic modalities
      for pulmonary hypertensive disorders.

PMID- 15994433
TI  - Gene transfer of neuronal nitric oxide synthase to carotid body reverses enhanced
      chemoreceptor function in heart failure rabbits.
AB  - Our previous studies showed that decreased nitric oxide (NO) production enhanced
      carotid body (CB) chemoreceptor activity in chronic heart failure (CHF) rabbits.
      In the present study, we investigated the effects of neuronal NO synthase (nNOS)
      gene transfer on CB chemoreceptor activity in CHF rabbits. The nNOS protein
      expression and NO production were suppressed in CBs (P<0.05) of CHF rabbits, but
      were increased 3 days after application of an adenovirus expressing nNOS
      (Ad.nNOS) to the CB. As a control, nNOS and NO levels in CHF CBs were not
      affected by Ad.EGFP. Baseline single-fiber discharge during normoxia and the
      response to hypoxia were enhanced (P<0.05) from CB chemoreceptors in CHF versus
      sham rabbits. Ad.nNOS decreased the baseline discharge (4.5+/-0.3 versus 7.3+/
      0.4 imp/s at 105+/-1.9 mm Hg) and the response to hypoxia (18.3+/-1.2 imp/s
      versus 35.6+/-1.1 at 40+/-2.1 mm Hg) from CB chemoreceptors in CHF rabbits
      (Ad.nNOS CB versus contralateral noninfected CB respectively, P<0.05). A specific
      nNOS inhibitor, S-Methyl-L-thiocitrulline (SMTC), fully inhibited the effect of
      Ad.nNOS on the enhanced CB activity in CHF rabbits. In addition, nNOS gene
      transfer to the CBs also significantly blunted the baseline renal sympathetic
      nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits
      (P<0.05). These results indicate that decreased endogenous nNOS activity in the
      CB plays an important role in the enhanced activity of the CB chemoreceptors and
      peripheral chemoreflex function in CHF rabbits.

PMID- 15994434
TI  - Signaling pathways involved in adenosine triphosphate-induced endothelial cell
      barrier enhancement.
AB  - Endothelial barrier dysfunction caused by inflammatory agonists is a frequent
      underlying cause of vascular leak and edema. Novel strategies to preserve barrier
      integrity could have profound clinical impact. Adenosine triphosphate (ATP)
      released from endothelial cells by shear stress and injury has been shown to
      protect the endothelial barrier in some settings. We have demonstrated that ATP
      and its nonhydrolyzed analogues enhanced barrier properties of cultured
      endothelial cell monolayers and caused remodeling of cell-cell junctions.
      Increases in cytosolic Ca2+ and Erk activation caused by ATP were irrelevant to
      barrier enhancement. Experiments using biochemical inhibitors or siRNA indicated
      that G proteins (specifically Galphaq and Galphai2), protein kinase A (PKA), and
      the PKA substrate vasodilator-stimulated phosphoprotein were involved in ATP
      induced barrier enhancement. ATP treatment decreased phosphorylation of myosin
      light chain and specifically activated myosin-associated phosphatase. Depletion
      of Galphaq with siRNA prevented ATP-induced activation of myosin phosphatase. We
      conclude that the mechanisms of ATP-induced barrier enhancement are independent
      of intracellular Ca2+, but involve activation of myosin phosphatase via a novel G
      protein-coupled mechanism and PKA.

PMID- 15994435
TI  - Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in early
      cardiomyogenesis by regulating canonical Wnt signaling.
AB  - We have recently reported that activation of phosphatidylinositol 3-kinase (PI3K)
      plays a critical role in the early stage of cardiomyocyte differentiation of
      P19CL6 cells. We here examined molecular mechanisms of how PI3K is involved in
      cardiomyocyte differentiation. DNA chip analysis revealed that expression levels
      of Wnt-3a were markedly increased and that the Wnt/beta-catenin pathway was
      activated temporally during the early stage of cardiomyocyte differentiation of
      P19CL6 cells. Activation of the Wnt/beta-catenin pathway during this period was
      required and sufficient for cardiomyocyte differentiation of P19CL6 cells.
      Inhibition of the PI3K/Akt pathway suppressed the Wnt/beta-catenin pathway by
      activation of glycogen synthase kinase-3beta (GSK-3beta) and degradation of beta
      catenin. Suppression of cardiomyocyte differentiation by inhibiting the PI3K/Akt
      pathway was rescued by forced expression of a nonphosphorylated, constitutively
      active form of beta-catenin. These results suggest that the PI3K pathway
      regulates cardiomyocyte differentiation through suppressing the GSK-3beta
      activity and maintaining the Wnt/beta-catenin activity.

PMID- 15994436
TI  - Optical action potential upstroke morphology reveals near-surface transmural
      propagation direction.
AB  - The analysis of surface-activation patterns and measurements of conduction
      velocity in ventricular myocardium is complicated by the fact that the electrical
      wavefront has a complex 3D shape and can approach the heart surface at various
      angles. Recent theoretical studies suggest that the optical upstroke is sensitive
      to the subsurface orientation of the wavefront. Our goal here was to (1)
      establish the quantitative relationship between optical upstroke morphology and
      subsurface wavefront orientation using computer modeling and (2) test theoretical
      predictions experimentally in isolated coronary-perfused swine right ventricular
      preparations. We show in numerical simulations that by suitable placement of
      linear epicardial stimulating electrodes, the angle phi of wavefronts with
      respect to the heart surface can be controlled. Using this method, we developed
      theoretical predictions of the optical upstroke shape dependence on phi. We
      determined that the level VF* at which the rate of rise of the optical upstroke
      reaches the maximum linearly depends on phi. A similar relationship was found in
      simulations with epicardial point stimulation. The optical mapping data were in
      good agreement with theory. Plane waves propagating parallel to myocardial fibers
      produced upstrokes with VF*<0.5, consistent with theoretical predictions for
      phi>0. Similarly, we obtained good agreement with theory for plane waves
      propagating in a direction perpendicular to fibers (VF*>0.5 when phi<0). Finally,
      during epicardial point stimulation, we discovered characteristic saddle-shaped
      VF* maps that were in excellent agreement with theoretically predicted changes in
      phi during wavefront expansion. Our findings should allow for improved
      interpretation of the results of optical mapping of intact heart preparations.

PMID- 15994437
TI  - Identification and characterization of vascular calcification-associated factor,
      a novel gene upregulated during vascular calcification in vitro and in vivo.
AB  - OBJECTIVE: Vascular calcification, with its increasing clinical sequelae,
      presents an important and unresolved dilemma in cardiac and vascular practice. We
      aimed to identify molecules involved in this process to develop strategies for
      treatment or prevention. METHODS AND RESULTS: Using subtractive hybridization, a
      novel cDNA, designated vascular calcification-associated factor (VCAF), has been
      isolated from a bovine retinal pericyte cDNA library generated during the
      differentiation and mineralization of these cells in vitro. RNA ligase-mediated
      rapid amplification of cDNA ends was used to compile the 740-bp bovine cDNA
      sequence. Database searching reveals that VCAF has novel nucleotide/amino acid
      sequences. RNA analysis confirms that VCAF is upregulated in mineralized
      pericytes and is present in human calcified arteries but not noncalcified
      arteries. Protein analysis using a VCAF antibody confirms the presence of an 18
      kDa protein in calcified nodules but not in confluent pericytes. Adenoviral
      antisense VCAF gene delivery reduces VCAF protein levels and accelerates pericyte
      differentiation compared with controls. CONCLUSIONS: We demonstrate the isolation
      of a novel gene, VCAF, which is upregulated during vascular calcification in
      vitro and in vivo. Antisense VCAF gene delivery accelerates pericyte
      differentiation, implicating a role for VCAF in this clinically significant
      pathological process.

PMID- 15994438
TI  - Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates
      migration of vascular smooth muscle cells stimulated by angiotensin II.
AB  - BACKGROUND: Rho and its effector Rho-kinase/ROCK mediate cytoskeletal
      reorganization as well as smooth muscle contraction. Recent studies indicate that
      Rho and ROCK are critically involved in vascular remodeling. Here, we tested the
      hypothesis that Rho/ROCK are critically involved in angiotensin II (Ang II)
      induced migration of vascular smooth muscle cells (VSMCs) by mediating a specific
      signal cross-talk. METHODS AND RESULTS: Immunoblotting demonstrated that Ang II
      stimulated phosphorylation of a ROCK substrate, regulatory myosin phosphatase
      targeting subunit (MYPT)-1. Phosphorylation of MYPT-1 as well as migration of
      VSMCs induced by Ang II was inhibited by dominant-negative Rho (dnRho) or ROCK
      inhibitor, Y27632. Ang II-induced c-Jun NH2-terminal kinase (JNK) activation, but
      extracellular signal-regulated kinase (ERK) activation was not mediated through
      Rho/ROCK. Thus, infection of adenovirus encoding dnJNK inhibited VSMC migration
      by Ang II. We have further demonstrated that the Rho/ROCK activation by Ang II
      requires protein kinase C-delta (PKCdelta) and proline-rich tyrosine kinase 2
      (PYK2) activation, but not epidermal growth factor receptor transactivation.
      Also, VSMCs express PDZ-Rho guanine nucleotide exchange factor (GEF) and Ang II
      stimulated PYK2 association with tyrosine phosphorylated PDZ-RhoGEF. CONCLUSIONS:
      PKCdelta/PYK2-dependent Rho/ROCK activation through PDZ-RhoGEF mediates Ang II
      induced VSMC migration via JNK activation in VSMCs, providing a novel mechanistic
      role of the Rho/ROCK cascade that is involved in vascular remodeling.

PMID- 15994439
TI  - Shear stress induces endothelial differentiation from a murine embryonic
      mesenchymal progenitor cell line.
AB  - OBJECTIVE: Recent studies have illustrated that mesenchymal stem cells possess
      the potential to differentiate along an endothelial lineage, but the effect of
      shear on mesenchymal differentiation is unknown. Thus, we developed an in vitro
      shear stress system to examine the relationship between shear stress and the
      endothelial differentiation of a murine embryonic mesenchymal progenitor cell
      line, C3H/10T1/2. METHODS AND RESULTS: The parallel plate system of fluid shear
      stress was used. Shear stress significantly induced expression of mature
      endothelial cell-specific markers in CH3H/10T1/2 cells such as CD31, von
      Willebrand factor, and vascular endothelial-cadherin at both the mRNA and protein
      levels with real-time polymerase chain reaction and immunofluorescence analyses,
      respectively. In addition, shear-induced augmentation of functional markers of
      the mature endothelial phenotype such as uptake of acetylated low-density
      lipoproteins and formation of capillary-like structures on Matrigel. Furthermore,
      shear stress significantly upregulated angiogenic growth factors while
      downregulating growth factors associated with smooth muscle cell differentiation.
      CONCLUSIONS: This study demonstrates, for the fist time, endothelial
      differentiation in a mesenchymal progenitor CH3H/10T1/2 cell line resulting from
      shear exposure. Thus, this analysis may serve as a basis for further
      understanding the effect of shear on mesenchymal and vascular cell
      differentiation.

PMID- 15994440
TI  - Atherosclerotic lesion development in a novel ovary-intact mouse model of
      perimenopause.
AB  - OBJECTIVE: Since the unexpected results from the Women's Health Initiative, the
      possible protective role of estrogen in preventing heart disease in
      perimenopausal and postmenopausal women is uncertain. This study examined
      atherosclerotic lesion development in ovariectomized versus follicle-depleted
      ovary-intact cholesterol-fed female low-density lipoprotein (LDL) receptor
      deficient mice. METHODS AND RESULTS: We studied lesion development in LDL
      receptor-deficient mice that were ovariectomized or follicle depleted with 4
      vinylcyclohexene diepoxide (VCD) to induce ovarian failure, then treated +/-
      exogenous 17beta-estradiol via pellet implant. At 120 days after start of
      cholesterol feeding, the extent of lesion in aorta and innominate artery was
      determined. Lesion area in both locations was similar in vehicle control, VCD
      treated, and ovariectomized mice. Replacement with 17beta-estradiol caused lesion
      reduction (P<0.05) in both arterial locations, but it was most efficacious in
      suppressing innominate lesion area in VCD-treated mice (12.9+/-5.2%) compared
      with ovariectomized mice (40.0+/-6.04%). CONCLUSIONS: Endocrine status associated
      with the follicle-depleted ovary influences exogenous estradiol effects during
      the development of atherosclerotic lesions and, in particular, inhibits lesion
      progression in the innominate artery.

PMID- 15994441
TI  - Heparin-binding epidermal growth factor-like growth factor, collateral vessel
      development, and angiogenesis in skeletal muscle ischemia.
AB  - OBJECTIVE: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is
      a potent mitogen for smooth muscle cells and has been implicated in
      atherosclerosis, tissue regeneration after ischemia, vascular development, and
      tumor angiogenesis. We examined the hypothesis that HB-EGF participates in
      angiogenesis and collateral growth in ischemia. METHODS AND RESULTS: During 3
      weeks after femoral artery ligation, no attenuation occurred in recovery of
      hindlimb perfusion or distal saphenous artery flow in HB-EGF-null (HB-EGF(-/-))
      versus wild-type mice. Lumen diameters of remodeled collaterals in gracilis
      muscle were similar by morphometry (87+/-8 versus 94+/-6 microm) and angiography,
      although medial thickening was reduced. Gastrocnemius muscle underwent comparable
      angiogenesis (41% and 33% increase in capillary-to-muscle fiber ratio). Renal
      renin mRNA, arterial pressure, and heart rate during anesthesia or conscious
      unrestrained conditions were similar between groups. These latter findings
      validate comparisons of perfusion data and also suggest that differences in
      arterial pressure and/or renin-angiotensin activity are not masking an otherwise
      inhibitory effect of HB-EGF absence. Four days after ligation, EGF receptor
      phosphorylation increased in muscle by 104% in wild-type but by only 30% in HB
      EGF(-/-) mice. This argues against compensation by other EGF receptor ligands.
      CONCLUSIONS: Our results suggest that HB-EGF is not required for arteriogenesis
      or angiogenesis in hindlimb ischemia.

PMID- 15994442
TI  - Overexpression of human apolipoprotein A-II in transgenic mice does not impair
      macrophage-specific reverse cholesterol transport in vivo.
AB  - BACKGROUND: Overexpression of human apolipoprotein (apo) A-II in transgenic mice
      induces high-density lipoprotein (HDL) deficiency, and increased atherosclerosis
      susceptibility only when fed an atherogenic diet. This may, in part, be caused by
      impairment in reverse cholesterol transport (RCT). METHODS AND RESULTS:
      [3H]cholesterol-labeled macrophages were injected intraperitoneally into mice
      maintained on a chow diet or an atherogenic diet. Plasma [3H]cholesterol did not
      differ from human apoA-II transgenic and control mice at 24 or 48 hours after the
      label injection. On the chow diet, human apoA-II transgenic mice presented
      increased [3H]cholesterol in liver (1.3-fold) and feces (6-fold) compared with
      control mice (P<0.05). The magnitude of macrophage-specific RCT did not differ
      between transgenic and control mice fed the atherogenic diet. CONCLUSIONS: Human
      apoA-II maintains effective RCT from macrophages to feces in vivo despite an HDL
      deficiency. These findings suggest that the increased atherosclerotic lesions
      observed in apoA-II transgenic mice fed an atherogenic diet are not caused by
      impairment in macrophage-specific RCT.

PMID- 15994443
TI  - Cytoplasmic expression and extracellular deposition of an antiangiogenic factor,
      pigment epithelium-derived factor, in human atherosclerotic plaques.
AB  - OBJECTIVE: To assess the expression and distribution of a
      neurotrophic/antiangiogenic factor, pigment epithelium-derived factor (PEDF),
      related to angiogenesis that is a possibly key event during atherogenesis in
      human atherosclerotic plaques. METHODS AND RESULTS: Twenty fresh aortic samples
      were used for reverse-transcription polymerase chain reaction (RT-PCR), Western
      blot, and immunohistochemistry (IHC). In addition, 80 stocked paraffin blocks of
      coronary arteries from 40 autopsy cases were also used. IHC revealed divergent
      staining patterns for PEDF in both the aortas and the coronary arteries tested,
      ie, "cytoplasmic staining" or "extracellular deposition," were observed,
      respectively. In the areas showing cytoplasmic staining, double PEDF was
      expressed in a majority of the foamy macrophages and in some smooth muscle cells,
      and the PEDF-positive cell frequency was positively correlated with that of
      microvessels in a cell-rich area in the coronary arteries (P<0.0001). Inversely,
      extracellular deposition of PEDF was seen in acellular areas and was negatively
      correlated with the number of microvessels (P=0.0003). CONCLUSIONS: These results
      suggest that PEDF may function as an antiangiogenic factor when it is deposited
      onto the extracellular matrix. Thus, PEDF may play a significant role in
      determining the balance of angiogenesis/ antiangiogenesis during atherogenesis.

PMID- 15994444
TI  - PPARalpha, but not PPARgamma, activators decrease macrophage-laden
      atherosclerotic lesions in a nondiabetic mouse model of mixed dyslipidemia.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor (PPAR) alpha and gamma are
      nuclear receptors that may modulate atherogenesis, not only by correcting
      metabolic disorders predisposing to atherosclerosis but also by directly acting
      at the level of the vascular wall. The accumulation of lipid-laden macrophages in
      the arterial wall is an early pivotal event participating in the initiation and
      promotion of atherosclerotic lesion formation. Because PPARalpha and gamma
      modulate macrophage gene expression and cellular function, it has been suggested
      that their ligands may modulate atherosclerosis development via direct effects on
      macrophages. In this report, we investigated the effect of a PPARalpha ligand
      (fenofibrate) and 2 PPARgamma ligands (rosiglitazone and pioglitazone) on
      atherogenesis in a dyslipidemic nondiabetic murine model that develops
      essentially macrophage-laden lesions. METHODS AND RESULTS: Mice were fed a
      Western diet supplemented or not with fenofibrate (100 mpk), rosiglitazone (10
      mpk), or pioglitazone (40 mpk) for 10 weeks. Atherosclerotic lesions together
      with metabolic parameters were measured after treatment. Fenofibrate treatment
      significantly improved lipoprotein metabolism toward a less atherogenic phenotype
      but did not affect insulin sensitivity. Contrarily, rosiglitazone and
      pioglitazone improved glucose homeostasis, whereas they did not improve
      lipoprotein metabolism. Fenofibrate treatment significantly decreased the
      accumulation of lipids and macrophages in the aortic sinus. However,
      surprisingly, neither rosiglitazone nor pioglitazone had an effect on lesion
      lipid accumulation or macrophage content. CONCLUSIONS: These results indicate
      that in a dyslipidemic nondiabetic murine model, PPARalpha, but not PPARgamma,
      activators protect against macrophage foam cell formation.

PMID- 15994445
TI  - The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes:
      a comprehensive study of molecular and biochemical findings in 13 unrelated
      Italian families.
AB  - OBJECTIVE: To better understand the role of lecithin:cholesterol acyltransferase
      (LCAT) in lipoprotein metabolism through the genetic and biochemical
      characterization of families carrying mutations in the LCAT gene. METHODS AND
      RESULTS: Thirteen families carrying 17 different mutations in the LCAT gene were
      identified by Lipid Clinics and Departments of Nephrology throughout Italy. DNA
      analysis of 82 family members identified 15 carriers of 2 mutant LCAT alleles, 11
      with familial LCAT deficiency (FLD) and 4 with fish-eye disease (FED). Forty-four
      individuals carried 1 mutant LCAT allele, and 23 had a normal genotype. Plasma
      unesterified cholesterol, unesterified/total cholesterol ratio, triglycerides,
      very-low-density lipoprotein cholesterol, and pre-beta high-density lipoprotein
      (LDL) were elevated, and high-density lipoprotein (HDL) cholesterol,
      apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II,
      cholesterol esterification rate, LCAT activity and concentration, and LDL and
      HDL3 particle size were reduced in a gene-dose-dependent manner in carriers of
      mutant LCAT alleles. No differences were found in the lipid/lipoprotein profile
      of FLD and FED cases, except for higher plasma unesterified cholesterol and
      unesterified/total cholesterol ratio in the former. CONCLUSIONS: In a large
      series of subjects carrying mutations in the LCAT gene, the inheritance of a
      mutated LCAT genotype causes a gene-dose-dependent alteration in the plasma
      lipid/lipoprotein profile, which is remarkably similar between subjects
      classified as FLD or FED.

PMID- 15994446
TI  - High-frequency transtemporal sonothrombolysis.

PMID- 15994447
TI  - Coxiella burnetii and atypical respiratory infectious burden in stroke.

PMID- 15994448
TI  - The risk and benefit of endarterectomy in women with symptomatic internal carotid
      artery disease.

PMID- 15994449
TI  - Organizing stroke systems of care.

PMID- 15994450
TI  - Mechanical embolus removal: a new day dawning.

PMID- 15994451
TI  - Pharmacogenomics: harbinger for the era of personalized medicine?

PMID- 15994452
TI  - The origins of pharmacology in the 16th century.

PMID- 15994453
TI  - CYP3A probes can quantitatively predict the in vivo kinetics of other CYP3A
      substrates and can accurately assess CYP3A induction and inhibition.
AB  - Because the rates at which therapeutics are cleared from the body can affect
      their effectiveness, knowing and accounting for the variables that contribute to
      drug clearance is of utmost importance when designing a drug dosage regimen for
      patients. The activities of the manifold cytochrome P450 enzymes [(CYPs), the
      most clinically important of which is often CYP3A] must be considered as they are
      essential for modification and metabolism of compounds (i.e., therapeutic,
      xenobiotic, etc.) prior to their excretion. To this end, much research has been
      expended on trying to identify and develop drug probes that accurately predict
      the metabolism of CYP3A substrates in individuals. Recently, Benet has written on
      the futility of such an enterprise; however, other researchers believe the
      identification of valuable predictive probes is not only possible but crucial.

PMID- 15994454
TI  - Functional selectivity, ligand-directed trafficking, conformation-specific
      agonism: what's in a name?
AB  - Research on the design of compounds to selectively affect specific subsets of
      signals downstream of receptors has burgeoned lately, and several reports
      discussed at Experimental Biology 2005 indicate progress is being made in the
      understanding of what makes a drug functionally selective. Different
      conformations adopted by receptors after associating with specific ligands can
      determine which intracellular signaling pathways get activated and which do not.
      The appeal of such specific compounds is enormous when one considers that many
      disease states might require the subtle manipulation of some (or even one) but
      not all downstream events stemming from specific receptor activation.
      Additionally, a better understanding of functional selectivity would likely
      improve the drug delivery process: if compounds are screened through several
      functional assays appropriately designed to look for compounds exhibiting a high
      degree of selectivity, then many potential lead compounds might not be as
      frequently overlooked.

PMID- 15994455
TI  - A G protein-coupled receptor for estrogen: the end of the search?
AB  - The effects of estrogen on responsive cells and organismic development have long
      been known and well documented. Estrogen binds to the estrogen receptor, a dimer
      of the complex translocates to the nucleus, binds specific DNA elements and
      regulates the transcription of particular genes, a process that takes some time
      to achieve. One of the curious findings of intense estrogen research-that some
      estrogen-dependent effects appear to occur immediately-has led to the conclusion
      that quick responses are mediated by an estrogen binding protein(s) in the
      cytoplasm or located at the plasma membrane. Hasbi et al. chart the course
      through which several characterized estrogen binding proteins (not necessarily
      sharing sequence similarity beyond the estrogen binding domain) were discovered,
      including most notably, the orphan G protein-coupled receptor GPR30. And what is
      to be made of differing accounts of GPR30's intracellular whereabouts?

PMID- 15994456
TI  - The cardiotoxicology of anthracycline chemotherapeutics: translating molecular
      mechanism into preventative medicine.
AB  - Anthracyclines remain a mainstay of chemotherapy in spite of their well
      recognized cardiotoxicity. Recent experience with trastuzumab (Herceptin) and
      anthracycline therapy has prompted a detailed analysis of the function of erbB2
      in the heart. These studies demonstrate a cardioprotective effect of neuregulin,
      the endogenous ligand for the erbB4/erbB2 heterodimeric receptor complex.
      Although the mechanisms of cytoprotection remain incompletely understood, these
      studies have triggered the question of whether physiological manipulation of
      cardioprotective pathways that involve erbB can be used to improve outcome in
      patients treated with anthracyclines. The local activation of cardioprotection by
      cardiovascular exercise may be such a manipulation and warrants further
      investigation.

PMID- 15994458
TI  - Improved microarray methods for profiling the Yeast Knockout strain collection.
AB  - A remarkable feature of the Yeast Knockout strain collection is the presence of
      two unique 20mer TAG sequences in almost every strain. In principle, the relative
      abundances of strains in a complex mixture can be profiled swiftly and
      quantitatively by amplifying these sequences and hybridizing them to microarrays,
      but TAG microarrays have not been widely used. Here, we introduce a TAG
      microarray design with sophisticated controls and describe a robust method for
      hybridizing high concentrations of dye-labeled TAGs in single-stranded form. We
      also highlight the importance of avoiding PCR contamination and provide
      procedures for detection and eradication. Validation experiments using these
      methods yielded false positive (FP) and false negative (FN) rates for individual
      TAG detection of 3-6% and 15-18%, respectively. Analysis demonstrated that cross
      hybridization was the chief source of FPs, while TAG amplification defects were
      the main cause of FNs. The materials, protocols, data and associated software
      described here comprise a suite of experimental resources that should facilitate
      the use of TAG microarrays for a wide variety of genetic screens.

PMID- 15994457
TI  - Discovery and therapeutic promise of selective androgen receptor modulators.
AB  - Androgens are essential for male development and the maintenance of male
      secondary characteristics, such as bone mass, muscle mass, body composition, and
      spermatogenesis. The main disadvantages of steroidal androgens are their
      undesirable physicochemical and pharmacokinetic properties. The recent discovery
      of nonsteroidal selective androgen receptor modulators (SARMs) provides a
      promising alternative for testosterone replacement therapies with advantages
      including oral bioavailability, flexibility of structural modification, androgen
      receptor specificity, tissue selectivity, and the lack of steroid-related side
      effects.

PMID- 15994459
TI  - Characterization of a novel transcriptionally active domain in the transforming
      growth factor beta-regulated Smad3 protein.
AB  - Transforming growth factor beta (TGFbeta) regulates transcriptional responses via
      activation of cytoplasmic effector proteins termed Smads. Following their
      phosphorylation by the type I TGFbeta receptor, Smads form oligomers and
      translocate to the nucleus where they activate the transcription of TGFbeta
      target genes in cooperation with nuclear cofactors and coactivators. In the
      present study, we have undertaken a deletion analysis of human Smad3 protein in
      order to characterize domains that are essential for transcriptional activation
      in mammalian cells. With this analysis, we showed that Smad3 contains two domains
      with transcriptional activation function: the MH2 domain and a second middle
      domain that includes the linker region and the first two beta strands of the MH2
      domain. Using a protein-protein interaction assay based on biotinylation in vivo,
      we were able to show that a Smad3 protein bearing an internal deletion in the
      middle transactivation domain is characterized by normal oligomerization and
      receptor activation properties. However, this mutant has reduced transactivation
      capacity on synthetic or natural promoters and is unable to interact physically
      and functionally with the histone acetyltransferase p/CAF. The loss of
      interaction with p/CAF or other coactivators could account, at least in part, for
      the reduced transactivation capacity of this Smad3 mutant. Our data support an
      essential role of the previously uncharacterized middle region of Smad3 for
      nuclear functions, such as transcriptional activation and interaction with
      coactivators.

PMID- 15994460
TI  - Archaeal Hel308 helicase targets replication forks in vivo and in vitro and
      unwinds lagging strands.
AB  - Mutations in mammalian and Drosophila Hel308 and PolQ paralogues cause genome
      instability but their helicase functions are mysterious. By in vivo and in vitro
      analysis, we show that Hel308 from archaea (Hel308a) may act at stalled
      replication forks. Introducing hel308a into Escherichia coli dnaE strains that
      conditionally accumulate stalled forks caused synthetic lethality, an effect
      indistinguishable from E.coli RecQ. Further analysis in vivo indicated that the
      effect of hel308a is exerted independently of homologous recombination. The
      minimal biochemical properties of Hel308a protein were the same as human Hel308.
      We describe how helicase actions of Hel308a at fork structures lead specifically
      to displacement of lagging strands. The invading strand of D-loops is also
      targeted. Using archaeal Hel308, we propose models of action for the helicase
      domain of PolQ, promoting loading of the translesion polymerase domain. We
      speculate that removal of lagging strands at stalled forks by Hel308 promotes the
      formation of initiation zones, priming restart of lagging strand synthesis.

PMID- 15994462
TI  - Sepsis induces diaphragm electron transport chain dysfunction and protein
      depletion.
AB  - RATIONALE: Sepsis significantly alters skeletal muscle mitochondrial function,
      but the mechanisms responsible for this abnormality are unknown. OBJECTIVES: We
      postulated that endotoxin elicits specific changes in electron transport chain
      proteins that produce derangements in mitochondrial function. To examine this
      issue, we compared the effects of endotoxin-induced sepsis on mitochondrial ATP
      (adenosine triphosphate) formation and electron transport chain protein
      composition. METHODS AND MEASUREMENTS: Diaphragm mitochondrial oxygen consumption
      and mitochondrial nicotinamide adenine dinucleotide, reduced form, oxidase assays
      were measured in control rats (n=13) and rats given endotoxin (8 mg/kg/d) for 12
      (n=14), 24 (n=14), 36 (n=14), and 48 h (n=13). Electron transport chain subunits
      from Complexes I, III, IV, and V were isolated using Blue Native polyacrylamide
      gel electrophoresis techniques. MAIN RESULTS: Endotoxin administration: 1)
      elicited large reductions in mitochondrial oxygen consumption (e.g., 201+/-3.9 SE
      natoms O/min/mg for controls and 101+/-4.5 SE natoms O/minutes/mg after 48 h
      endotoxin, p<0.001), in nicotinamide adenine dinucleotide, reduced form, oxidase
      activity (p<0.002), and in uncoupled respiration (p<0.001) and 2) induced
      selective reductions in two subunits of Complex I, three subunits of Complex III,
      one subunit of Complex IV, and one subunit of Complex V. The time course of
      depletion of protein subunits mirrored alterations in oxygen consumption.
      CONCLUSIONS: Our data indicate that endotoxin selectively depletes critical
      components of the electron transport chain that diminishes electron flow, reduces
      proton pumping and decreases ATP formation.

PMID- 15994461
TI  - A case-crossover analysis of out-of-hospital coronary deaths and air pollution in
      Rome, Italy.
AB  - RATIONALE: Out-of-hospital coronary heart disease death is a major public health
      problem, but the association with air pollution is not well understood.
      OBJECTIVES: We evaluated the association between daily ambient air pollution
      levels (particle number concentration [PNC]--a proxy for ultrafine particles
      [diameter < 0.1 microm], mass of particles with diameter less than 10 microm
      [PM10]; CO, NO2, and O3) and the occurrence of fatal, nonhospitalized coronary
      events. METHODS: Subjects were 5,144 out-of-hospital fatalities (410-414,
      International Classification of Diseases-9; 1998-2000) who had been residents of
      Rome. Hospitalizations during the 3 yr before death were considered to identify
      comorbidities (e.g., diabetes, hypertension, heart failure, dysrhythmia, chronic
      obstructive pulmonary disease). Statistical analyses were performed using a case
      crossover design. MEASUREMENTS AND MAIN RESULTS: The association with out-of
      hospital coronary deaths was statistically significant for PNC, PM10, and CO. Air
      pollution on the day of death had the strongest effect (e.g., 7.6% increase [95%
      confidence interval, 2.0-13.6%]) for an interquartile range of PNC, 27,790
      particles/cm3. The 65-74- and 75+-yr age groups were at higher risk than the 35
      64-yr age group, and there was a suggestion of effect modification for people
      with hypertension and chronic obstructive pulmonary disease. CONCLUSIONS: Air
      pollutants originating from combustion processes, including ultrafine particles,
      are related to fatal, nonhospitalized coronary events. The effect is stronger
      among people over 65 years of age, but is not limited to a group with a specific
      comorbidity.

PMID- 15994463
TI  - Alveolar surfactant protein D content modulates bleomycin-induced lung injury.
AB  - RATIONALE: Surfactant protein D (SP-D) is a collectin family member with
      demonstrated immunomodulatory properties in vitro. We hypothesized that SP-D
      modulates inflammation during noninfectious lung injury in vivo. OBJECTIVES: To
      investigate the association of alveolar SP-D and injury, we studied the responses
      of transgenic mice expressing varying levels of SP-D to intratracheal bleomycin
      (ITB). METHODS: Eight-week old C57/BL6 SP-D-deficient (-/-) mice and syngeneic
      wild-type (WT) controls or Swiss Black SP-D-overexpressing (SP-D OE) mice and
      littermate controls received either ITB or saline and were followed for up to 21
      d. MEASUREMENTS AND RESULTS: Kaplan-Meier analysis demonstrated a dose-dependent
      decrease in survival in ITB SP-D (-/-) mice receiving 2 U/kg bleomycin, with a 14
      d mortality of 100% versus 0% mortality for WT receiving 2 U/kg ITB or SP-D (-/-)
      mice given saline (p < 0.05). At 8 d, ITB SP-D (-/-) mice had greater respiratory
      distress (frequency/tidal volume) and weight loss than ITB WT mice. Furthermore,
      bronchoalveolar lavage cellularity, pulmonary parenchymal inflammation, and
      tissue 3-nitrotyrosine (NO2 Y) were increased to a greater extent in ITB SP-D (-/
      ) mice. By 21 d, compared with all groups, ITB SP-D (-/-) survivors had increased
      Trichrome staining and tissue hydroxyproline levels. As proof of principle, SP-D
      OE mice were highly resistant to bleomycin-induced morbidity and mortality at
      doses up to 3 U/kg. CONCLUSIONS: These data provide new in vivo evidence for an
      antiinflammatory role for SP-D in response to noninfectious, subacute lung injury
      via modulation of oxidative-nitrative stress.

PMID- 15994464
TI  - Pulmonary hypertension.
AB  - The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and
      Richards pioneered right-heart catheterization. Until that time, no direct
      measurement of central vascular pressure had been performed in humans. Right
      heart catheterization ignited an explosion of insights into function and
      dysfunction of the pulmonary circulation, cardiac performance, ventilation
      perfusion relationships, lung-heart interactions, valvular function, and
      congenital heart disease. It marked the beginnings of angiocardiography with its
      diagnostic implications for diseases of the left heart and peripheral
      circulation. Pulmonary hypertension was discovered to be the consequence of a
      large variety of diseases that either raised pressure downstream of the pulmonary
      capillaries, induced vasoconstriction, increased blood flow to the lung, or
      obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic
      vasoconstriction was found to be a major cause of acute and chronic pulmonary
      hypertension, and surprising vasoreactivity of the pulmonary vascular bed was
      discovered to be present in many cases of severe pulmonary hypertension,
      initially in mitral stenosis. Diseases as disparate as scleroderma, cystic
      fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have
      shared consequences in the pulmonary circulation. Some of the achievements of
      Cournand and Richards and their scientific descendents are discussed in this
      article, including success in the diagnosis and treatment of idiopathic pulmonary
      arterial hypertension, chronic thromboembolic pulmonary hypertension, and
      management of hypoxic pulmonary hypertension.

PMID- 15994465
TI  - NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine
      model of sleep apnea.
AB  - RATIONALE: Persons with obstructive sleep apnea may have significant residual
      hypersomnolence, despite therapy. Long-term hypoxia/reoxygenation events in adult
      mice, simulating oxygenation patterns of moderate-severe sleep apnea, result in
      lasting hypersomnolence, oxidative injury, and proinflammatory responses in wake
      active brain regions. We hypothesized that long-term intermittent hypoxia
      activates brain NADPH oxidase and that this enzyme serves as a critical source of
      superoxide in the oxidation injury and in hypersomnolence. OBJECTIVES: We sought
      to determine whether long-term hypoxia/reoxygenation events in mice result in
      NADPH oxidase activation and whether NADPH oxidase is essential for the
      proinflammatory response and hypersomnolence. METHODS: NADPH oxidase gene and
      protein responses were measured in wake-active brain regions in wild-type mice
      exposed to long-term hypoxia/reoxygenation. Sleep and oxidative and
      proinflammatory responses were measured in adult mice either devoid of NADPH
      oxidase activity (gp91phox-null mice) or in which NADPH oxidase activity was
      systemically inhibited with apocynin osmotic pumps throughout
      hypoxia/reoxygenation. MAIN RESULTS: Long-term intermittent hypoxia increased
      NADPH oxidase gene and protein responses in wake-active brain regions. Both
      transgenic absence and pharmacologic inhibition of NADPH oxidase activity
      throughout long-term hypoxia/reoxygenation conferred resistance to not only long
      term hypoxia/reoxygenation hypersomnolence but also to carbonylation, lipid
      peroxidation injury, and the proinflammatory response, including inducible nitric
      oxide synthase activity in wake-active brain regions. CONCLUSIONS: Collectively,
      these findings strongly support a critical role for NADPH oxidase in the lasting
      hypersomnolence and oxidative and proinflammatory responses after
      hypoxia/reoxygenation patterns simulating severe obstructive sleep apnea
      oxygenation, highlighting the potential of inhibiting NADPH oxidase to prevent
      oxidation-mediated morbidities in obstructive sleep apnea.

PMID- 15994466
TI  - Hepatocyte growth factor is required for alveologenesis in the neonatal rat.
AB  - RATIONALE: Our core hypothesis is that growth factors that have dysregulated
      expression during experimental neonatal lung injury are likely to be involved in
      normal postnatal lung growth and alveologenesis. OBJECTIVES: To determine if
      hepatocyte growth factor (HGF) is upregulated in neonatal lung injury and is
      essential for postnatal alveologenesis. METHODS: A neonatal lung injury, in which
      there were patchy areas of interstitial thickening with a relative increase in
      the proportion of epithelial cells, was induced in newborn rats by exposing them
      to 60% oxygen for 14 days. Air-exposed pups had binding of endogenous HGF to its
      natural receptor, c-Met, inhibited by the intraperitoneal injection of either
      neutralizing antibody to HGF, or a truncated soluble c-Met receptor. MEASUREMENTS
      AND MAIN RESULTS: The 60% oxygen-mediated lung injury was associated with
      increased lung mRNAs for hepatocyte growth factor and c-Met, relative to air
      exposed control lungs, at Day 7 after birth. After exposure to 60% oxygen,
      immunoreactive HGF was increased at Days 4 and 7, and immunoreactive c-Met was
      increased at Day 14. In air-exposed pups, intraperitoneal injections of
      neutralizing antibody to HGF inhibited DNA synthesis in alveoli-forming secondary
      crests, and reduced the number of alveoli in 6-day-old pups. Intraperitoneal
      injections of a truncated soluble c-Met receptor inhibited DNA synthesis in
      secondary crests in 4-day-old air-exposed rat pups. CONCLUSIONS: HGF and its c
      Met receptor are required for normal postnatal alveolar formation from secondary
      crests, and are upregulated during 60% oxygen-induced neonatal lung injury.

PMID- 15994467
TI  - Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by
      healthy volunteers.
AB  - RATIONALE: Salmeterol is a beta2-adrenoreceptor agonist used in the treatment of
      obstructive pulmonary disease. Salmeterol inhibits inflammatory responses by
      neutrophils and mononuclear cells in vitro and in mouse models of lung
      inflammation in vivo. OBJECTIVE: To determine the effect of salmeterol on LPS
      induced lung inflammation in humans. METHODS: Thirty-two healthy subjects were
      enrolled in a single-blinded, placebo-controlled study. Subjects inhaled 100
      microg salmeterol or placebo (t=-0.5 h) followed by 100 microg LPS or normal
      saline (t=0 h; n=8/group). Measurements were performed in bronchoalveolar lavage
      fluid and purified alveolar macrophages obtained 6 h post-challenge. MEASUREMENTS
      AND MAIN RESULTS: Inhalation of LPS was associated with neutrophil influx,
      neutrophil degranulation (myeloperoxidase, bactericidal/permeability-increasing
      protein and elastase), release of cytokines (tumor necrosis factor alpha and
      interleukin 6) and chemokines (interleukin 8, epithelial cell-derived neutrophil
      attractant 78, macrophage inflammatory proteins 1alpha and 1beta), activation of
      alveolar macrophages (upregulation of HLA-DR and CD71; enhanced expression of
      mRNAs for 13 different mediators of inflammation), and protein leakage (all
      p<0.05 vs. placebo/saline). Pretreatment with salmeterol inhibited LPS-induced
      neutrophil influx, neutrophil degranulation (myeloperoxidase), tumor necrosis
      factor alpha release, and HLA-DR expression (all p<0.05 vs. placebo/LPS), while
      not significantly influencing other responses. CONCLUSION: Salmeterol exerts
      antiinflammatory effects in the pulmonary compartment of humans exposed to LPS.

PMID- 15994468
TI  - Rhinovirus viremia in children with respiratory infections.
AB  - RATIONALE: Viremia has been implicated in many viral infections; however, viremia
      due to rhinovirus (RV; rhinoviremia) has been considered not to occur in normal
      individuals. OBJECTIVE: To evaluate whether RV enters the bloodstream and
      identify the possible risk factors. METHODS: Nasopharyngeal washes (NPWs) of 221
      children with respiratory infections were examined for the presence of RV by
      reverse transcription-polymerase chain reaction. Blood from 88 children, whose
      NPW was RV-positive, and 31 of RV-negative control subjects was subsequently
      examined for the presence of RV in the blood by semi-nested reverse transcription
      polymerase chain reaction. Rhinoviremia was then correlated with clinical
      characteristics of the disease. RESULTS: RV was detected in the blood of 10 out
      of 88 NPW RV-positive cases (11.4%): 7 of 28 children with asthma exacerbations
      (25.0%), 2 of 26 with common cold (7.7%), 1 of 25 with bronchiolitis (4.0%), and
      0 of 9 with pneumonia (0%). All NPW RV-negative cases were negative in the blood.
      The proportion of rhinoviremia in children with asthma exacerbation was
      significantly higher compared with children suffering from the other diseases (25
      vs. 5%, p = 0.01). Significant risk factors were: sampling <or= 24 hours from
      symptom initiation, personal history of asthma, and male sex. Age, fever, family,
      and personal history of atopy did not affect the presence of RV in the blood.
      CONCLUSIONS: Viremia may occur during RV respiratory infections in normal
      children and is rather common in the early course of acute asthma exacerbations,
      suggesting that rhinoviremia may be involved in asthma exacerbation pathogenesis.

PMID- 15994469
TI  - Screening for bipolar disorder in patients treated for depression in a family
      medicine clinic.
AB  - PURPOSE: The prevalence of bipolar disorder in patients being treated for
      depression with antidepressants in a family medicine clinic was investigated in
      this study. METHODS: Adult patients with depression who were treated with an
      antidepressant in a general outpatient family medicine clinic at the University
      of Texas were screened for bipolar disorder using the Mood Disorder Questionnaire
      (MDQ), a brief self-report inventory. A subsample of subjects received the
      Structured Clinical Interview based on the DSM-IV (SCID) to test the operating
      characteristics of the MDQ in this population. RESULTS: of the patients taking an
      antidepressant for depression, 21.3% screened positive for bipolar disorder on
      the MDQ. These patients were somewhat younger, more likely to be white, more
      likely to be living alone, much less likely to be married, and less likely to be
      employed than those who screen negative. Nearly two thirds of those screened
      positive had never received diagnosis of bipolar disorder. The sensitivity and
      specificity of the MDQ in this population, after adjusting for the sampling
      protocol, were 0.580 (0.454 to 0.706, 95% CI) and 0.930 (0.878 to 0.981, 95% CI)
      respectively. CONCLUSION: Bipolar disorder frequently occurs in patients being
      treated with antidepressants in primary care settings. Most are unrecognized and
      undiagnosed. Screening for bipolar disorder in such patients may improve
      recognition, identification, and appropriate treatment.

PMID- 15994470
TI  - Screening for dementia: family caregiver questionnaires reliably predict
      dementia.
AB  - INTRODUCTION: Because of increasing numbers of patients with diseases that cause
      dementia, primary care physicians must use efficient assessment procedures in
      their clinics. Important advantages of screening for dementia include
      determination of the patient's cognitive capacity to participate competently in
      his/her own medical care and early diagnosis, which enables administration of
      medications that preserve some cognitive functions. METHODS: A study was
      conducted to determine whether questionnaires completed by a family caregiver
      about a patient could differentiate between those with dementia and those with
      other neurological disorders that do not cause dementia. Clinical and demographic
      information gleaned from more than 330 consecutive multidisciplinary outpatient
      dementia clinic assessments were entered into an Institutional Review Board
      approved database and analyzed post hoc to answer several research questions.
      RESULTS: Three questionnaires completed by family caregivers about patients were
      able to differentiate reliably between patients with dementia with a variety of
      degenerative disorders and patients without dementia with other neurological
      disorders that often are mistaken for dementia. When these questionnaires are
      combined with a patient test (Mini-Mental State Examination), an accurate
      prediction of which patients suffer from a true degenerative disease that causes
      dementia was robust (effect size of R2 = 0.81, P <.0001 for the multiple logistic
      regression analysis). DISCUSSION: These instruments assist the primary care
      physician to determine which patients seem to suffer from a disease that causes
      dementia and need further assessment by the physician or at a specialized
      dementia clinic. The ultimate goal is to assure that patients receive appropriate
      medical management as early in the disease process as possible.

PMID- 15994471
TI  - Help-seeking for insomnia among adult patients in primary care.
AB  - OBJECTIVE: To clarify the patient characteristics associated with seeking medical
      help for insomnia. METHODS: A consecutive sample (n = 700) of adults attending a
      non-urgent primary care appointment was screened for sleep problems. A follow-up
      mailed survey then assessed insomnia symptoms, daytime impairment, beliefs about
      sleep, medication use, sleepiness and fatigue, and medical help-seeking. RESULTS:
      Fifty-two percent of patients with probable insomnia reported discussing this
      with a physician. Multivariate logistic regression analyses indicated that
      discussing one's probable insomnia with a physician was independently associated
      with having a greater number of medical conditions (OR, 2.19 [95% CI, 1.13 to
      4.22]), being more highly educated (1.67 [95% CI, 1.11 to 2.51]), sleeping less
      per night (OR, 0.71 [95% CI, 0.52 to 0.96]), and greater perceived daytime
      impairment due to insomnia (OR, 2.07 [95% CI, 1.06 to 4.03]). CONCLUSIONS:
      Primary care patients often seek medical help when they experience insomnia.
      Clinical treatment ought to especially target poor sleepers presenting with
      significant insomnia-related impairment, medical morbidity, or both. Future
      research should further clarify the role of medical and psychiatric comorbidities
      and determine whether resolution of insomnia and its consequences improves the
      outcomes of common medical conditions.

PMID- 15994472
TI  - How much time do patients with diabetes spend on self-care?
AB  - INTRODUCTION: Little is reported about how much time patients spend on self
      management, a cornerstone of diabetes care. METHODS: We studied a cross-section
      of 1482 diabetic patients enrolled in 3 northeastern United States managed care
      plans. Patients were surveyed about how much time they spent on foot care,
      exercise, and food shopping/preparation (7/00 to 9/01). Logistic regressions
      modeled which types of patients were likely to spend time, and linear regressions
      modeled characteristics associated with spending more/less time. RESULTS:
      Patients (57.9% > or = 55 years; 51.6% women; 36.2% African American; 31.1% on
      insulin) spent 58 (mean) minutes/day on self-care (interquartile range 19, 84).
      Many patients skipped individual self-care elements: 37.9% reported no foot care,
      37.7% no exercise, and 54.4% no time on food shopping/preparation. One fourth of
      patients with severe foot neuropathy symptoms spent no time on foot care. Never
      self-testers were less likely than others to engage in foot care (odds ratio (OR)
      0.4 (95% CI 0.3, 0.6), exercise (OR 0.4 (95% CI 0.3, 0.6)), and food
      shopping/preparation (OR 0.7 (95% CI 0.5, 1.0)), and were likely to spend 30
      minutes less total self-care time than frequent self-testers (P <.01).
      DISCUSSION: Most people spent considerable time engaged in self-care, but many
      skipped individual tasks, offering clinicians opportunities for collaborative
      decision making.

PMID- 15994473
TI  - Is your depressed patient bipolar?
AB  - Accurate diagnosis of mood disorders is critical for treatment to be effective.
      Distinguishing between major depression and bipolar disorders, especially the
      depressed phase of a bipolar disorder, is essential, because they differ
      substantially in their genetics, clinical course, outcomes, prognosis, and
      treatment. In current practice, bipolar disorders, especially bipolar II
      disorder, are underdiagnosed. Misdiagnosing bipolar disorders deprives patients
      of timely and potentially lifesaving treatment, particularly considering the
      development of newer and possibly more effective medications for both depressive
      features and the maintenance treatment (prevention of recurrence/relapse). This
      article focuses specifically on how to recognize the identifying features
      suggestive of a bipolar disorder in patients who present with depressive symptoms
      or who have previously been diagnosed with major depression or dysthymia. This
      task is not especially time-consuming, and the interested primary care or family
      physician can easily perform this assessment. Tools to assist the physician in
      daily practice with the evaluation and recognition of bipolar disorders and
      bipolar depression are presented and discussed.

PMID- 15994474
TI  - Depression in US Hispanics: diagnostic and management considerations in family
      practice.
AB  - US Hispanics, currently the largest minority group in the country, face
      disparities in the recognition and treatment of major depression. This article
      provides an evidence-based review of the prevalence, presentation, and management
      of major depression in primary care in this heterogeneous ethnic group. Under
      recognition of depression in adult Hispanic Americans may be related to language
      differences, health literacy barriers, somatic presentations, and use of cultural
      idioms of distress. Hispanic patients are often agreeable to treatment but as a
      group may tend to prefer psychotherapy or combined counseling and medication to
      pharmacotherapy alone. Recent studies have found both psychological and
      pharmacologic treatment options are efficacious in this minority group. Treatment
      adherence should be actively monitored to help ensure its effectiveness. To help
      reduce the number of depressed Hispanic patients who pass through primary care
      undetected or inadequately treated, family physicians should make a concerted
      effort to increase their awareness of the presentation of major depression in
      this population and actively promote adherence to effective treatments.

PMID- 15994475
TI  - Family medicine in Cuba: community-oriented primary care and complementary and
      alternative medicine.
AB  - Family physicians in Cuba and the United States operate within very different
      health systems. Cuba's health system is notable for achieving developed country
      health outcomes despite a developing country economy. The authors of this study
      traveled to Cuba and reviewed the literature to investigate which practices of
      Cuban family physicians might be applicable for US family physicians wishing to
      learn from the Cuban experience. We found that community-oriented primary care
      (COPC) and complementary and alternative medicine (CAM) are well developed within
      the Cuban medical system. Because COPC and CAM are already recommended by US
      family medicine professional bodies, US family physicians may want to learn from
      the Cuban experience and perhaps incorporate elements into their individual
      practices.

PMID- 15994476
TI  - Medication abortion and family physicians' scope of practice.

PMID- 15994478
TI  - Use of external abdominal ice to complete external cephalic version in term
      breech pregnancy.
AB  - A 36-year-old multiparous woman with fetus in the breech position applied ice to
      the fundus of the uterus and achieved successful cephalic version. No other
      reports of using ice to induce cephalic version are found with MEDLINE search;
      however, it has been used as a folk remedy. Further research to evaluate the
      efficacy and safety of ice is needed to determine whether it increases cephalic
      vaginal birth.

PMID- 15994477
TI  - Maternal postpartum health care utilization and the effect of Minnesota early
      discharge legislation.
AB  - PURPOSE: To describe maternal postdischarge follow-up and health care utilization
      in the context of Minnesota's early discharge legislation, which mandates
      coverage for a home visit for a mother and baby who voluntarily leave the
      hospital early. METHODS: Claims data from a large managed care organization were
      used to identify 22,944 women giving birth from January 1995 through February
      1999. Study variables included home or clinic visits within 1 week of discharge
      (early follow-up), readmissions within 1 month of discharge, and urgent care or
      emergency department visits within 2 months of discharge. RESULTS: After
      enactment of Minnesota's legislation, the percentage of mothers with short stays
      decreased from 52% to 16% for vaginal births and from 87% to 63% for cesarean
      births (P =.001). Overall, 33% of mothers with vaginal births and 40% with
      cesarean births had early home or clinic follow-up (P =.001). Mothers who stayed
      0 or 1 hospital days after vaginal births were more likely to have early follow
      up than those with longer stays (37% vs 32%, P =.01). However, mothers who stayed
      2 or 3 days after cesarean birth were no more likely to have early follow-up than
      mothers who stayed 4 or more days (39% vs 42%, P =.08). Rates of early follow-up
      were significantly higher after enactment of Minnesota's legislation, regardless
      of length of stay. CONCLUSIONS: Implementation of Minnesota's early discharge
      legislation corresponded with significantly increased lengths of stay and an
      increase in the percentage of mothers who received early follow-up visits.
      However the majority of mothers with short stays continued to lack early follow
      up.

PMID- 15994479
TI  - Paget-Schroetter syndrome in the young and active.
AB  - We report this case of effort thrombosis of the upper extremity (Paget-Schroetter
      syndrome) caused by hypertrophied muscles. This unusual cause of extrinsic venous
      compression and intimal injury leading to thrombosis was treated uniquely with
      good outcome. Untreated symptomatic patients can sustain long-term disability
      from venous obstruction resulting in significant loss of occupational
      productivity and quality of life. For the same reason, early catheter directed
      thrombolysis followed by anticoagulation and surgical intervention are
      recommended in much of the recent literature. Thrombolysis is the most common
      form of treatment, followed by surgery, if needed, after careful diagnostic
      approach. A majority of the literature supports a multimodal approach, but there
      is no definite consensus on management. This highlights the need for randomized
      clinical trials to guide management as well as to assess the safety and efficacy
      of anticoagulants commonly used and to define the optimal duration of therapy
      after thrombolysis.

PMID- 15994480
TI  - Warthin tumor: a common, benign tumor presenting as a highly suspicious mass.

PMID- 15994481
TI  - AAFP Convocation of Practices and Network: report from the 2005 annual meeting.

PMID- 15994482
TI  - Newborn tongue-tie and breast-feeding.

PMID- 15994484
TI  - Postvasectomy semen analysis.

PMID- 15994486
TI  - Excess factor VIII and hypercoagulability.

PMID- 15994489
TI  - 125.

PMID- 15994490
TI  - Fusion research. ITER Finds a home--with a whopping mortgage.

PMID- 15994491
TI  - Space science. Solar-sail enthusiasts say mission lost, possibly in space.

PMID- 15994493
TI  - 2006 funding. Senate squeezes NSF's budget.

PMID- 15994492
TI  - U.S. budget. House 'peer review' kills two NIH grants.

PMID- 15994494
TI  - Climate change. Senate resolution backs mandatory emission limits.

PMID- 15994495
TI  - Foundations. Joining forces for brain tumor research.

PMID- 15994496
TI  - Public health. Gates Foundation picks winners in Grand Challenges in Global
      Health.

PMID- 15994497
TI  - Ecology. Flying on the edge: bluebirds make use of habitat corridors.

PMID- 15994498
TI  - Science in Iran. Hard-liner's triumph puts research plans in doubt.

PMID- 15994499
TI  - Nanotechnology. EPA ponders voluntary nanotechnology regulations.

PMID- 15994500
TI  - 2006 budget. Can Congress save NASA science?

PMID- 15994501
TI  - Condensed-matter physics. Flowing crystals flummox physicists.

PMID- 15994502
TI  - Condensed-matter physics. The quirks and culture of helium.

PMID- 15994503
TI  - Climate change. Atlantic climate pacemaker for millennia past, decades hence?

PMID- 15994505
TI  - Central Asia. Combating radioactive risks and isolation in Tajikistan.

PMID- 15994504
TI  - Astronomy. Suitcase-sized space telescope fills a big stellar niche.

PMID- 15994506
TI  - Central Asia. Shock and recovery.

PMID- 15994507
TI  - What can be done to stop the decline?

PMID- 15994508
TI  - Arguing about the use of stem cells.

PMID- 15994509
TI  - Evangelical biologists and evolution.

PMID- 15994510
TI  - Debating whale sanctuaries.

PMID- 15994511
TI  - When will the oil run out?

PMID- 15994512
TI  - Recalculating future oil reserves.

PMID- 15994513
TI  - Comment on "children creating core properties of language: evidence from an
      emerging sign language in Nicaragua".

PMID- 15994515
TI  - Global voices of science. Ascent of nanoscience in China.

PMID- 15994516
TI  - Nanotechnology. Small things and big changes in the developing world.

PMID- 15994517
TI  - Materials science. Expanding the molecular electronics toolbox.

PMID- 15994518
TI  - Ecology. Food web ecology: playing Jenga and beyond.

PMID- 15994519
TI  - Astronomy. Masers in the sky.

PMID- 15994520
TI  - Genetics. Themes and variations in apicomplexan parasite biology.

PMID- 15994521
TI  - What don't we know?

PMID- 15994522
TI  - In praise of hard questions.

PMID- 15994523
TI  - What is the universe made of?

PMID- 15994524
TI  - So much more to know.

PMID- 15994525
TI  - What is the biological basis of consciousness?

PMID- 15994526
TI  - Why do humans have so few genes?

PMID- 15994527
TI  - To what extent are genetic variation and personal health linked?

PMID- 15994528
TI  - Can the laws of physics be unified?

PMID- 15994529
TI  - How much can human life span be extended?

PMID- 15994530
TI  - What controls organ regeneration?

PMID- 15994531
TI  - How can a skin cell become a nerve cell?

PMID- 15994533
TI  - How does Earth's interior work?

PMID- 15994532
TI  - How does a single somatic cell become a whole plant?

PMID- 15994534
TI  - Are we alone in the universe?

PMID- 15994535
TI  - How and where did life on Earth arise?

PMID- 15994536
TI  - What determines species diversity?

PMID- 15994537
TI  - What genetic changes made us uniquely human?

PMID- 15994538
TI  - How are memories stored and retrieved?

PMID- 15994539
TI  - How did cooperative behavior evolve?

PMID- 15994540
TI  - How will big pictures emerge from a sea of biological data?

PMID- 15994541
TI  - How far can we push chemical self-assembly?

PMID- 15994542
TI  - What are the limits of conventional computing?

PMID- 15994544
TI  - Do deeper principles underlie quantum uncertainty and nonlocality?

PMID- 15994543
TI  - Can we selectively shut off immune responses?

PMID- 15994545
TI  - Is an effective HIV vaccine feasible?

PMID- 15994546
TI  - How hot will the greenhouse world be?

PMID- 15994547
TI  - What can replace cheap oil--and when?

PMID- 15994548
TI  - Will Malthus continue to be wrong?

PMID- 15994549
TI  - Genome analysis reveals pili in Group B Streptococcus.
AB  - Pili are essential virulence factors in many Gram-negative bacteria; however,
      they have not been described in most important Gram-positive pathogens. While
      screening the sequence of multiple genomes of Group B Streptococcus, we
      identified protective antigens that formed high molecular weight polymers.
      Immunogold electron microscopy revealed that the structures have a pilus-like
      form. These large structures have gone unrecognized in decades of studies of
      Group B Streptococcus.

PMID- 15994550
TI  - A high-pressure structure in curium linked to magnetism.
AB  - Curium lies at the center of the actinide series and has a half-filled shell with
      seven 5f electrons spatially residing inside its radon core. As a function of
      pressure, curium exhibits five different crystallographic phases up to 100
      gigapascals, of which all but one are also found in the preceding element,
      americium. We describe here a structure in curium, Cm III, with monoclinic
      symmetry, space group C2/c, found at intermediate pressures (between 37 and 56
      gigapascals). Ab initio electronic structure calculations agree with the observed
      sequence of structures and establish that it is the spin polarization of curium's
      5f electrons that stabilizes Cm III. The results reveal that curium is one of a
      few elements that has a lattice structure stabilized by magnetism.

PMID- 15994551
TI  - On-wire lithography.
AB  - We report a high-throughput procedure for lithographically processing one
      dimensional nanowires. This procedure, termed on-wire lithography, combines
      advances in template-directed synthesis of nanowires with electrochemical
      deposition and wet-chemical etching and allows routine fabrication of face-to
      face disk arrays and gap structures in the range of five to several hundred
      nanometers. We studied the transport properties of 13-nanometer gaps with and
      without nanoscopic amounts of conducting polymers deposited within by dip-pen
      nanolithography.

PMID- 15994552
TI  - Atlantic Ocean forcing of North American and European summer climate.
AB  - Recent extreme events such as the devastating 2003 European summer heat wave
      raise important questions about the possible causes of any underlying trends, or
      low-frequency variations, in regional climates. Here, we present new evidence
      that basin-scale changes in the Atlantic Ocean, probably related to the
      thermohaline circulation, have been an important driver of multidecadal
      variations in the summertime climate of both North America and western Europe.
      Our findings advance understanding of past climate changes and also have
      implications for decadal climate predictions.

PMID- 15994553
TI  - GRIP deuterium excess reveals rapid and orbital-scale changes in Greenland
      moisture origin.
AB  - The Northern Hemisphere hydrological cycle is a key factor coupling ice sheets,
      ocean circulation, and polar amplification of climate change. Here we present a
      Northern Hemisphere deuterium excess profile covering one climatic cycle,
      constructed with the use of delta18O and deltaD Greenland Ice Core Project (GRIP)
      records. Past changes in Greenland source and site temperatures are quantified
      with precipitation seasonality taken into account. The imprint of obliquity is
      evidenced in the site-to-source temperature gradient at orbital scale. At the
      millennial time scale, GRIP source temperature changes reflect southward shifts
      of the geographical locations of moisture sources during cold events, and these
      rapid shifts are associated with large-scale changes in atmospheric circulation.

PMID- 15994554
TI  - A magnetic nanoprobe technology for detecting molecular interactions in live
      cells.
AB  - Technologies to assess the molecular targets of biomolecules in living cells are
      lacking. We have developed a technology called magnetism-based interaction
      capture (MAGIC) that identifies molecular targets on the basis of induced
      movement of superparamagnetic nanoparticles inside living cells. Efficient
      intracellular uptake of superparamagnetic nanoparticles (coated with a small
      molecule of interest) was mediated by a transducible fusogenic peptide. These
      nanoprobes captured the small molecule's labeled target protein and were
      translocated in a direction specified by the magnetic field. Use of MAGIC in
      genome-wide expression screening identified multiple protein targets of a drug.
      MAGIC was also used to monitor signal-dependent modification and multiple
      interactions of proteins.

PMID- 15994555
TI  - Cell-to-cell transfer of bacterial outer membrane lipoproteins.
AB  - Myxococcus xanthus cells can glide forward by retracting type IV pili. Tgl, an
      outer membrane lipoprotein, is necessary to assemble pili. Tgl mutants can be
      transiently "stimulated" if brought into end-to-end contact with tgl+ donor
      cells. By separating the stimulated recipient cells from donor cells, we found
      that Tgl protein was transferred from the donors to the rescued recipient cells.
      Mutants lacking CglB lipoprotein, which is part of a second gliding engine, could
      also be stimulated, and CglB protein was transferred from donor to recipient
      cells. The high transfer efficiency of Tgl and CglB proteins suggests that donor
      and recipient cells briefly fuse their outer membranes.

PMID- 15994556
TI  - Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase.
AB  - Ubiquitination controls a broad range of cellular functions. The last step of the
      ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3
      enzymes are responsible for substrate specificity and catalyze the formation of
      an isopeptide bond between a lysine residue of the substrate (or the N terminus
      of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases
      encoded by Kaposi's sarcoma-associated herpesvirus that mediate the
      ubiquitination of major histocompatibility complex class I (MHC I) molecules and
      subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down
      regulation of MHC I molecules lacking lysine residues in their intracytoplasmic
      domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and
      their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike
      lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue
      in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a
      single cysteine residue in an artificial glycine and alanine intracytoplasmic
      domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination
      can occur on proteins lacking accessible lysines or an accessible N terminus.

PMID- 15994558
TI  - Genome sequence of Theileria parva, a bovine pathogen that transforms
      lymphocytes.
AB  - We report the genome sequence of Theileria parva, an apicomplexan pathogen
      causing economic losses to smallholder farmers in Africa. The parasite
      chromosomes exhibit limited conservation of gene synteny with Plasmodium
      falciparum, and its plastid-like genome represents the first example where all
      apicoplast genes are encoded on one DNA strand. We tentatively identify proteins
      that facilitate parasite segregation during host cell cytokinesis and contribute
      to persistent infection of transformed host cells. Several biosynthetic pathways
      are incomplete or absent, suggesting substantial metabolic dependence on the host
      cell. One protein family that may generate parasite antigenic diversity is not
      telomere-associated.

PMID- 15994559
TI  - Long-term monitoring of bacteria undergoing programmed population control in a
      microchemostat.
AB  - Using an active approach to preventing biofilm formation, we implemented a
      microfluidic bioreactor that enables long-term culture and monitoring of
      extremely small populations of bacteria with single-cell resolution. We used this
      device to observe the dynamics of Escherichia coli carrying a synthetic
      "population control" circuit that regulates cell density through a feedback
      mechanism based on quorum sensing. The microfluidic bioreactor enabled long-term
      monitoring of unnatural behavior programmed by the synthetic circuit, which
      included sustained oscillations in cell density and associated morphological
      changes, over hundreds of hours.

PMID- 15994560
TI  - Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured
      region.
AB  - Cell signaling that culminates in posttranslational modifications directs protein
      activity. Here we report how multiple Ca2+-dependent phosphorylation sites within
      the transcription activator Ets-1 act additively to produce graded DNA binding
      affinity. Nuclear magnetic resonance spectroscopic analyses show that
      phosphorylation shifts Ets-1 from a dynamic conformation poised to bind DNA to a
      well-folded inhibited state. These phosphates lie in an unstructured flexible
      region that functions as the allosteric effector of autoinhibition. Variable
      phosphorylation thus serves as a "rheostat" for cell signaling to fine-tune
      transcription at the level of DNA binding.

PMID- 15994561
TI  - Effects of landscape corridors on seed dispersal by birds.
AB  - Habitat fragmentation threatens biodiversity by disrupting dispersal. The
      mechanisms and consequences of this disruption are controversial, primarily
      because most organisms are difficult to track. We examined the effect of habitat
      corridors on long-distance dispersal of seeds by birds, and tested whether small
      scale (<20 meters) movements of birds could be scaled up to predict dispersal of
      seeds across hundreds of meters in eight experimentally fragmented landscapes. A
      simulation model accurately predicted the observed pattern of seed rain and
      revealed that corridors functioned through edge-following behavior of birds. Our
      study shows how models based on easily observed behaviors can be scaled up to
      predict landscape-level processes.

PMID- 15994557
TI  - Genome of the host-cell transforming parasite Theileria annulata compared with T.
      parva.
AB  - Theileria annulata and T. parva are closely related protozoan parasites that
      cause lymphoproliferative diseases of cattle. We sequenced the genome of T.
      annulata and compared it with that of T. parva to understand the mechanisms
      underlying transformation and tropism. Despite high conservation of gene
      sequences and synteny, the analysis reveals unequally expanded gene families and
      species-specific genes. We also identify divergent families of putative secreted
      polypeptides that may reduce immune recognition, candidate regulators of host
      cell transformation, and a Theileria-specific protein domain [frequently
      associated in Theileria (FAINT)] present in a large number of secreted proteins.

PMID- 15994562
TI  - Identification of a universal Group B streptococcus vaccine by multiple genome
      screen.
AB  - Group B Streptococcus (GBS) is a multiserotype bacterial pathogen representing a
      major cause of life-threatening infections in newborns. To develop a broadly
      protective vaccine, we analyzed the genome sequences of eight GBS isolates and
      cloned and tested 312 surface proteins as vaccines. Four proteins elicited
      protection in mice, and their combination proved highly protective against a
      large panel of strains, including all circulating serotypes. Protection also
      correlated with antigen accessibility on the bacterial surface and with the
      induction of opsonophagocytic antibodies. Multigenome analysis and screening
      described here represent a powerful strategy for identifying potential vaccine
      candidates against highly variable pathogens.

PMID- 15994563
TI  - Integrating mental health in global initiatives for HIV/AIDS.
AB  - A more prominent role is needed for mental health interventions in global
      HIV/AIDS initiatives -- such as the World Health Organization'3 by 5' Initiative.
      Significant numbers of infected people have, or develop, mental health problems,
      and this often adversely impacts on HIV/AIDS treatment and adherence. Integrating
      psychiatric and psychosocial interventions should benefit both the mental and the
      physical health of people living with HIV/AIDS.

PMID- 15994564
TI  - The role of proteomics in investigating psychiatric disorders.
AB  - Proteomics is the study of protein expression and function on a genome-wide scale
      and its application in psychiatric research is relatively new. As protein
      expression is the mediator of genetic vulnerabilities, it is critical that this
      area is explored further to increase our understanding of psychiatric disease and
      reveal potential new treatments.

PMID- 15994565
TI  - Zero tolerance of violence by users of mental health services: the need for an
      ethical framework.
AB  - Concerns about violent conduct of service users towards healthcare staff have
      prompted a ;zero tolerance' policy within the National Health Service. This
      policy specifically excludes users of mental health services. We attempt to
      challenge artificial distinctions between users of mental health and other
      services, and propose an ethical underpinning to the implementation of this
      policy.

PMID- 15994566
TI  - Schizophrenia and suicide: systematic review of risk factors.
AB  - BACKGROUND: Suicide risk is greatly increased in schizophrenia. Detection of
      those at risk is clinically important. AIMS: To identify risk factors for suicide
      in schizophrenia. METHOD: The international literature on case-control and cohort
      studies of patients with schizophrenia or related conditions in which suicide was
      reported as an outcome was systematically reviewed. Studies were identified
      through searching electronic databases and reference lists, and by consulting
      experts. RESULTS: Twenty-nine eligible studies were identified. Factors with
      robust evidence of increased risk of suicide were previous depressive disorders
      (OR=3.03, 95% CI 2.06-4.46), previous suicide attempts (OR=4.09, 95% CI 2.79
      6.01), drug misuse (OR=3.21, 95% CI 1.99-5.17), agitation or motor restlessness
      (OR=2.61, 95% CI 1.54-4.41), fear of mental disintegration (OR=12.1, 95% CI 1.89
      81.3), poor adherence to treatment (OR=3.75, 95% CI 2.20-6.37) and recent loss
      (OR=4.03, 95% CI 1.37-11.8). Reduced risk was associated with hallucinations
      (OR=0.50, 95% CI 0.35-0.71). CONCLUSIONS: Prevention of suicide in schizophrenia
      is likely to result from treatment of affective symptoms, improving adherence to
      treatment, and maintaining special vigilance in patients with risk factors,
      especially after losses.

PMID- 15994567
TI  - Birth weight and psychological distress at age 45-51 years: results from the
      Aberdeen Children of the 1950s cohort study.
AB  - BACKGROUND: It is unclear whether the effect of low birth weight on common
      affective disorders in later life is direct or mediated through childhood
      factors. AIMS: To determine whether birth weight has a direct effect on
      psychological distress in adulthood not mediated by childhood IQ or behavioural
      problems. METHOD: Participants (n=5572) of the Aberdeen Children of the 1950s
      study had data on birth weight for gestational age and adult psychological
      distress. Logistic regression was used to examine the association between these
      factors, with adjustment for confounders and potential childhood mediators.
      RESULTS: Children born full term but weighing less than 5.5 lb had increased odds
      of psychological distress in later life after adjustment for potential
      confounders (OR=1.49, 95% CI 1.01-2.20). Further adjustment for childhood IQ and
      behaviour did not attenuate the association. A 1 s.d. decrease in birth weight
      for gestational age was associated with a 4% increased odds of psychological
      distress in adulthood (OR=1.04, 95% CI 0.97-1.12). CONCLUSIONS: Low birth weight
      for gestational age, particularly at term, was associated with adult
      psychological distress. This was not mediated by childhood factors, suggesting a
      direct effect of early life factors on adult mental health. A neurodevelopmental
      pathway may therefore be implicated.

PMID- 15994568
TI  - Geographical variation in rates of common mental disorders in Britain:
      prospective cohort study.
AB  - BACKGROUND: There is little geographical variation in the prevalence of the
      common mental disorders. However, there is little longitudinal research. AIMS: To
      estimate variance in rates of common mental disorders at individual, household
      and electoral ward levels prospectively. METHOD: A 12-month cohort study of 7659
      adults aged 16-74 years in 4338 private households, in 626 electoral wards. Data
      were collected as part of the British Household Panel Survey. Common mental
      disorders were assessed using the 12-item General Health Questionnaire (GHQ).
      Ward-level socio-economic deprivation was measured using the Carstairs index.
      RESULTS: Less than 1% of total variance, in onset and maintenance of common
      mental disorders and change in GHQ score between waves, occurred at ward level.
      However, 12% of variance, which is a statistically significant difference, was
      found at household level (a much smaller geographical unit) and this difference
      remained after further analyses. CONCLUSIONS: Ward level socio-economic
      deprivation does not influence the onset and maintenance of common mental
      disorders in Britain but local factors at the household level do. Reasons for
      this remain unclear.

PMID- 15994569
TI  - Physical health and depressive symptoms in older Europeans. Results from EURODEP.
AB  - BACKGROUND: Associations between physical health and depression are consistent
      across cultures among adults up to 65 years of age. In later life, the impact of
      physical health on depression is much more substantial and may depend on
      sociocultural factors. AIMS: To examine cross-national differences in the
      association between physical health and depressive symptoms in elderly people
      across western Europe. METHOD: Fourteen community-based studies on depression in
      later life in nine western European countries contributed to a total study sample
      of 22 570 respondents aged 65 years and older. Measures were harmonized for
      depressive symptoms (EURO-D scale), functional limitations and chronic physical
      conditions. RESULTS: In the majority of the participating samples, the
      association of depressive symptoms with functional disability was stronger than
      with chronic physical conditions. Associations were slightly more pronounced in
      the UK and Ireland. CONCLUSIONS: The association between physical health and
      depressive symptoms in later life is consistent across western Europe.

PMID- 15994570
TI  - Psychiatric hospitalisation and suicide among the very old in Denmark: population
      based register study.
AB  - BACKGROUND: Very old people have higher suicide rates than the younger elderly
      population. Psychiatric disorders are known to have a strong association with
      suicide among elderly people. AIMS: To analyse the analyse the suicide risk
      associated with psychiatric hospitalisation among the very old (> or =80 years)
      compared with the middle-aged (50-64 years) and old (65-79 years) populations.
      METHOD: Individual-level data on the entire Danish population aged 50 years or
      over were analysed for the period 1994-1998. Relative suicide risks were
      calculated using event-history analysis. RESULTS: Among 1978 527 persons, 2323
      died by suicide. Although the very old group exhibited a four-fold to five-fold
      increase in risk of suicide for those previously hospitalised, we noted an
      inverse interaction effect: the increase is distinctly smaller compared with that
      in the middle-aged and old groups. CONCLUSIONS: The association between suicide
      and psychiatric hospitalisation is much weaker for the very old than for the old.
      Psychiatric disorders among very old people may be interacting with other
      disorders, may be underdiagnosed or treated in other healthcare settings.

PMID- 15994571
TI  - Socio-economic inequalities in suicide: a European comparative study.
AB  - BACKGROUND: Social factors have been shown to be predictors of suicide. It is not
      known whether these factors vary between countries. AIMS: To present a first
      European overview of socio-economic inequalities in suicide mortality among men
      and women. METHOD: We used a prospective follow-up of censuses matched with vital
      statistics in ten European populations. Directly standardised rates of suicide
      were computed for each country. RESULTS: In men, a low level of educational
      attainment was a risk factor for suicide in eight out of ten countries. Suicide
      inequalities were smaller and less consistent in women. In most countries, the
      greater the socio-economic disadvantage, the higher is the risk of suicide. The
      population of Turin evidenced no socio-economic inequalities. CONCLUSIONS: Socio
      economic inequalities in suicide are a generalised phenomenon in western Europe,
      but the pattern and magnitude of these inequalities vary between countries. These
      inequalities call for improved access to psychiatric care for lower socio
      economic groups.

PMID- 15994572
TI  - Modafinil modulates anterior cingulate function in chronic schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with widespread cognitive deficits that
      have an impact on social function. Modafinil promotes wakefulness and is reported
      to enhance cognition. AIMS: To study the acute effects of modafinil
      administration upon brain activity and cognitive performance in people with
      chronic schizophrenia. METHOD: In a randomised double-blind placebo-controlled
      crossover design, 19 patients received either modafinil (100 mg) or placebo prior
      to undertaking a working memory task with functional magnetic resonance imaging.
      RESULTS: Seventeen patients completed the study and another underwent acute
      relapse 4 days post-drug. Modafinil administration was associated with
      significantly greater activation in the anterior cingulate cortex during the
      working memory task. The anterior cingulate cortex signal correlated with
      cognitive performance, although only a subset of patients exhibited
      'enhancement'. CONCLUSIONS: Modafinil modulates anterior cingulate cortex
      function in chronic schizophrenia but its beneficial cognitive effects may be
      restricted to a subset of patients requiring further characterisation.

PMID- 15994573
TI  - Domestic violence and its mental health correlates in Indian women.
AB  - BACKGROUND: Domestic spousal violence against women has far-reaching mental
      health implications. AIMS: To determine the association of domestic spousal
      violence with poor mental health. METHOD: In a household survey of rural, urban
      non-slum and urban slum areas from seven sites in India, the population of women
      aged 15-49 years was sampled using probability proportionate to size. The Self
      Report Questionnaire was used to assess mental health status and a structured
      questionnaire elicited spousal experiences of violence. RESULTS: Of 9938 women
      surveyed, 40% reported poor mental health. Logistic regression showed that women
      reporting 'any violence' -- 'slap', 'hit', 'kick' or 'beat' (OR 2.2, 95% CI 2.0
      2.5) -- or 'all violence' -- all of the four types of physically violent
      behaviour (OR 3.5, 95% CI 2.94-3.51) -- were at increased risk of poor mental
      health. CONCLUSIONS: Findings indicate a strong association between domestic
      spousal violence and poor mental health, and underscore the need for appropriate
      interventions.

PMID- 15994574
TI  - Outcomes of crises before and after introduction of a crisis resolution team.
AB  - BACKGROUND: Crisis resolution teams (CRTs) are being introduced throughout
      England, but their evidence base is limited. AIMS: To compare outcomes of crises
      before and after introduction of a CRT. METHOD: A new methodology was developed
      for identification and operational definition of crises. A quasi-experimental
      design was used to compare cohorts presenting just before and just after a CRT
      was established. RESULTS: Following introduction of the CRT, the admission rate
      in the 6 weeks after a crisis fell from 71% to 49% (OR 0.38, 95% CI 0.21-0.70). A
      difference of 5.6 points (95% CI 2.0-8.3) on mean Client Satisfaction
      Questionnaire (CSQ-8) score favoured the CRT. These findings remained significant
      after adjustment for baseline differences. No clear difference emerged in
      involuntary hospitalisations, symptoms, social functioning or quality of life.
      CONCLUSIONS: CRTs may prevent some admissions and patients prefer them, although
      other outcomes appear unchanged in the short term.

PMID- 15994575
TI  - Effectiveness of providing self-help information following acute traumatic
      injury: randomised controlled trial.
AB  - BACKGROUND: Patients attending an accident and emergency department may exhibit
      psychological disturbances post-injury. Early interventions have been suggested
      to reduce the risk of post-injury disorder, including psychoeducation. AIMS: We
      assessed the efficacy of providing such self-help information. METHOD: Patients
      who had experienced trauma were randomised to two groups: those given (n=75) and
      not given (n=67) a self-help booklet. Psychological assessments were completed
      within 2, 10-12 and 24-26 weeks. RESULTS: Post-traumatic stress disorder (PTSD),
      anxiety and depression decreased (P < 0.05) with time but there were no group
      differences in PTSD or anxiety. The controls were less depressed (P < 50.05) at
      follow-up. There was a reduction in PTSD caseness within the control (50%)
      compared with the intervention (20%) group which was almost significant (P <
      0.06). CONCLUSIONS: This trial failed to support the efficacy of providing self
      help information as a preventive strategy to ameliorate PTSD.

PMID- 15994576
TI  - Autism: functional brain mapping of exceptional calendar capacity.
AB  - BACKGROUND: 'Autistic savants' are individuals with autism who have extraordinary
      skills. Brain mechanisms underlying such capacities are still unknown. AIMS: To
      map the exceptional calendar capacity of a man with primary autism. METHOD:
      Positron emission tomography was used to map brain activity in a man who is able
      to associate a day of the week with the corresponding calendar date. RESULTS:
      During the calendar task, the left hippocampus, the left frontal cortex and the
      left middle temporal lobe were activated. CONCLUSIONS: The cerebral circuit
      involved in this man's prodigious calendar skill is similar to that normally
      involved in memory retrieval tasks. These results suggest that the prodigious
      capacities may be sustained by memory processing.

PMID- 15994577
TI  - 'Bipolarity' in bipolar disorder: distribution of manic and depressive symptoms
      in a treated population.
AB  - Cross-sectional analysis of 441 individuals with bipolar disorder treated at a US
      health maintenance organisation investigated the distribution of manic and
      depressive symptomsin that illness. Clinically significant depressive symptoms
      occurred in 94.1% of those with (hypo)mania, while 70.1% in a depressive episode
      had clinically significant manic symptoms. DSM-unrecognised depression-plus
      hypomania was over twice as prevalent as DSM-recognised mixed episodes.
      Depressive symptoms were unimodally distributed in (hypo)mania. Depressive and
      manic symptoms were positively, not inversely, correlated, and their co
      occurrence was associated with worse quality of life. Implications for the DSM
      and ICD nosological systems are discussed.

PMID- 15994578
TI  - Confounding factors for depression in adults with mild learning disability.

PMID- 15994579
TI  - Left frontal activation.

PMID- 15994580
TI  - Measures for mental health outcomes.

PMID- 15994581
TI  - Prevalence of dementia.

PMID- 15994582
TI  - Variations in involuntary commitment in the European Union.

PMID- 15994583
TI  - ECT for acute mania.

PMID- 15994585
TI  - Publication of case reports.

PMID- 15994586
TI  - Psychiatry in Europe.

PMID- 15994587
TI  - Decision making at the end of life: shifting sands.

PMID- 15994588
TI  - The use of patients for learning and maintaining practical skills.

PMID- 15994589
TI  - Multiple sclerosis: looking beyond autoimmunity.

PMID- 15994590
TI  - Disclosure of medical error: policies and practice.

PMID- 15994591
TI  - Lateral chest X-ray for physicians.

PMID- 15994592
TI  - Resolution of pericardial effusion after removal of ovarian fibroma--a Meigs'
      like syndrome.

PMID- 15994593
TI  - Chylothorax after coronary artery bypass surgery.

PMID- 15994594
TI  - Adult cirrhosis due to untreated congenital hypopituitarism.

PMID- 15994595
TI  - Hair analysis for drugs in child abuse.

PMID- 15994596
TI  - Neonatal pleural effusion and insertion of intercostal drain into the liver.

PMID- 15994597
TI  - Spontaneous liver rupture in Ehlers-Danlos syndrome type IV.

PMID- 15994598
TI  - Doctors as performance artists.

PMID- 15994599
TI  - 100 years of hormonology: a view from No. 1 Wimpole Street.

PMID- 15994600
TI  - Modern cardiopulmonary resuscitation--not so new after all.

PMID- 15994601
TI  - Nicotinic antagonists and nerve gas poisoning.

PMID- 15994602
TI  - The liver in metabolic syndrome.

PMID- 15994603
TI  - Autosurgery in women.

PMID- 15994604
TI  - Finger deformities in Renaissance art.

PMID- 15994605
TI  - Integrated teams.

PMID- 15994606
TI  - Parkinsonism in a ham-seller.

PMID- 15994607
TI  - Taking the sting out of needles.

PMID- 15994608
TI  - Updating the green journal.

PMID- 15994609
TI  - Arrested preterm labor: do the data support home or hospital care?

PMID- 15994610
TI  - Diagnosis of anal sphincter tears to prevent fecal incontinence: a randomized
      controlled trial.
AB  - OBJECTIVE: Maternal anal sphincter tears after vaginal delivery are frequently
      not diagnosed clinically and are associated with subsequent fecal incontinence.
      This study examined whether diagnosis of these tears by ultrasonography, followed
      by immediate surgical repair, reduces the occurrence of incontinence. METHODS: We
      conducted a randomized trial involving 752 primiparous women without a clinically
      evident anal sphincter tear to evaluate the benefit of adding endoanal
      ultrasonography immediately after vaginal delivery to the standard clinical
      examination of the perineum. When a sphincter tear was diagnosed, the perineum
      was surgically explored and the sphincter sutured. The main outcome evaluated was
      fecal incontinence 3 months postpartum graded by the Wexner incontinence scale,
      which measures incontinence to flatus and liquid or solid stools, need to wear a
      pad, and lifestyle alterations. RESULTS: Among women assessed by ultrasonography,
      5.6% had a sphincter tear. Severe incontinence was reported 3 months after
      childbirth by 3.3% of women in the intervention group compared with 8.7% in the
      control group (risk difference -5.4%; 95% confidence interval -8.9 to -2.0; P =
      .002). The benefit of the intervention persisted 1 year after delivery, with 3.2%
      severe incontinence in the intervention group compared with 6.7% in the control
      group (risk difference -3.5%; 95% confidence interval -6.8% to -0.3%; P = .03).
      Ultrasonography needs to be performed in 29 women to prevent 1 case of severe
      fecal incontinence. CONCLUSION: Ultrasound examination of the perineum after
      childbirth improves the diagnosis of anal sphincter tears, and their immediate
      repair decreases the risk of severe fecal incontinence. LEVEL OF EVIDENCE: I.

PMID- 15994611
TI  - Hospitalization for women with arrested preterm labor: a randomized trial.
AB  - OBJECTIVE: To determine whether hospitalization of women with arrested preterm
      labor has an effect on delivery at 36 weeks or greater when compared with women
      discharged home. METHODS: All women with a singleton gestation and a diagnosis of
      arrested preterm labor with intact membranes between 24 and 33 weeks, 4 days of
      gestation were randomly assigned to home or hospital management. Upon completion
      of a dexamethasone course, women assigned to outpatient management were promptly
      discharged, and women in the inpatient group were advised to continue
      hospitalization until 34 weeks. Decreased activity was encouraged in both groups.
      Bed rest was not strictly enforced. The primary outcome was delivery at 36 weeks
      or greater. RESULTS: A total of 101 women of a planned 188 were enrolled at the
      time of an interim analysis. There was no difference in the primary study outcome
      between the 2 groups and the trial was terminated. Among the hospitalized women,
      71% reached 36 weeks or greater, compared with 72% of those discharged home (P =
      .89). The mean cervical dilatation in hospitalized women was 2.7 +/- 0.5 cm,
      compared with 2.6 +/- 0.5 cm in women discharged home (P = .16). The overall
      length of hospital stay for the women allocated to hospitalization was 16 +/- 13
      days. CONCLUSION: Compared with hospitalization, outpatient management of women
      with arrested preterm labor and intact membranes had no effect on the rate of
      preterm birth. LEVEL OF EVIDENCE: I.

PMID- 15994612
TI  - Use of intrapartum antibiotics and the incidence of postnatal maternal and
      neonatal yeast infections.
AB  - OBJECTIVES: To estimate 1) the risk of candidiasis (neonatal thrush or breast
      infections or both) in nursing mother-infant pairs and 2) whether receipt of
      intrapartum antibiotics increases this risk. METHODS: Demographic and obstetric
      data were obtained at delivery, and telephone follow-up was obtained at 1 week
      and 1 and 3 months and recorded in the Lactation Services database, which was
      reviewed retrospectively. The diagnoses of thrush and breast candidiasis were
      based on symptoms and patient reports, as per standard clinical practice. For
      statistical analysis, chi(2) analysis and Student t test were used. A value of P
      < .05 was considered significant. RESULTS: A total of 811 nursing mother-infant
      pairs were seen between February 1, 2001, and August 31, 2002. Mother-infant
      pairs with follow-up who nursed for 1 month or longer were included (n = 435). Of
      these, 173 (39.8%) received intrapartum antibiotics, most (78.6%) for group B
      streptococci prophylaxis. Overall, 46 mother-infant pairs (10.6%) had either
      thrush or breast candidiasis (32 with both) within 1 month of delivery. Mothers
      who were exposed to intrapartum antibiotics were significantly more likely to
      develop breast candidiasis (odds ratio 2.1, 95% confidence interval 1.08-4.08).
      Antibiotic-exposed neonates were more likely to develop thrush, although this was
      not statistically significant. (odds ratio 1.87, 95% confidence interval 0.97
      3.63). Antibiotic-exposed infants were younger (mean +/- standard deviation, 38.5
      +/- 1.9 weeks compared with 39.0 +/- 1.3 weeks; P = .002), but there were no
      differences in maternal age, gravity or parity, or route of delivery.
      CONCLUSIONS: Neonatal thrush and maternal breast candidiasis are common early
      postnatal complications. The higher rates of thrush and breast candidiasis in
      antibiotic-exposed mother-infant pairs merits further study. LEVEL OF EVIDENCE:
      II-2.

PMID- 15994613
TI  - Nuchal cords in term and postterm deliveries--do we need to know?
AB  - OBJECTIVE: To analyze the effect of nuchal cords on perinatal features at
      delivery of term and postterm pregnancies. METHODS: A total of 11,748 women with
      planned vaginal deliveries, including 9,574 term and 2,174 postterm deliveries,
      were analyzed for intrapartum events, clinical peripartum management, mode of
      delivery, and neonatal outcome. The presence of nuchal cords was diagnosed
      clinically at the time of delivery. Data were obtained from our perinatal
      database between 1995 and 2004 for retrospective analysis. RESULTS: The incidence
      of nuchal cords in term and postterm deliveries was 33.7% and 35.1%,
      respectively. Multiple nuchal cords were present in 5.8% of term and 5.5% of
      postterm deliveries. Intrapartum signs of fetal compromise were increased in all
      groups, albeit not all reaching statistical significance in postterm deliveries.
      Meconium staining was significantly increased only in multiple nuchal cords of
      postterm deliveries (42.1% compared with 30.1%, P < .05). Mode of delivery was
      unchanged in all nuchal cord groups. Unfavorable neonatal blood gas values were
      significantly more frequent in all nuchal cord groups. Nevertheless, 5-minute
      Apgar scores less than 7 were not more common, and admission to neonatal unit was
      not required more frequently. Neonatal mean birth weight was significantly lower
      in all nuchal cord groups. CONCLUSION: Nuchal cords do not influence clinical
      management at delivery, and neonatal primary adaption is not impaired. Our data
      show that ultrasonographic nuchal cord assessment is not necessary at the time of
      admission for delivery. LEVEL OF EVIDENCE: II-3.

PMID- 15994614
TI  - A randomized controlled trial comparing fascia lata and synthetic mesh for sacral
      colpopexy.
AB  - OBJECTIVE: To compare the objective anatomic outcomes after sacral colpopexy
      performed with cadaveric fascia lata and polypropylene mesh. METHODS: Patients
      undergoing a sacral colpopexy were randomized to receive either fascia lata or
      polypropylene mesh in a double-blinded fashion. Data were collected at 6 weeks, 3
      months, 6 months, and 1 year postoperatively. The main outcome measures were
      pelvic organ prolapse quantification (POP-Q) system stage and individual POP-Q
      points over time. Objective anatomic failure was defined as POP-Q stage 2 or more
      at any point during the follow-up period. Proportions of patients with objective
      anatomic failure at 1 year in each group were compared using the chi(2) test.
      Mean POP-Q points and stage at 1 year were compared by using the independent
      samples t test. RESULTS: One hundred patients were randomized to receive either
      fascia (n = 46) or mesh (n = 54). Of the 89 patients returning for 1-year follow
      up, 91% (41/45) of the mesh group and 68% (30/44) of the fascia group were
      classified as objectively cured (P = .007). We found significant differences
      between the mesh and fascia groups with respect to the 1-year postoperative
      comparisons of points Aa, C, and POP-Q stage. There were no differences between
      the 2 groups with respect to points TVL (total vaginal length), GH (genital
      hiatus), PB (perineal body), Ap or Bp (2 points along the posterior vaginal
      wall). CONCLUSIONS: Polypropylene mesh was superior to fascia lata in terms of
      POP-Q points, POP-Q stage, and objective anatomic failure rates. LEVEL OF
      EVIDENCE: I.

PMID- 15994615
TI  - Long-term results with tension-free vaginal tape on mixed and stress urinary
      incontinence.
AB  - OBJECTIVE: To compare outcome of the tension-free vaginal tape (TVT) procedure in
      women with urinary mixed and stress incontinence. METHODS: A mailed questionnaire
      was answered by 760 of 970 women who had undergone TVT surgery 2-8 years ago (78%
      response rate). Seventeen women had unclassified incontinence, and 51 women who
      developed de novo urgency were excluded, giving 580 (83.8%) with stress
      incontinence and 112 (16.2%) women with mixed incontinence eligible for analysis.
      Demographic, reproductive factors, and medical history were obtained. The
      questionnaire included detailed questions about urinary symptoms. Analysis of
      outcome was done for cohorts by number of years since the operation. RESULTS: The
      women with stress incontinence had a persistent cure rate of 85% from 2 to 8
      years after the TVT procedure. The women with mixed incontinence had a persistent
      cure rate of 60% up to 4 years postoperatively, but the cure rate then steadily
      declined to 30% from 4 to 8 years after surgery. The increased rate of
      incontinence was due to urgency symptoms. CONCLUSION: The results of this study
      indicate that initial good cure rates of TVT for mixed incontinence do not
      persist after 4 years. LEVEL OF EVIDENCE: III.

PMID- 15994616
TI  - Prospective data collection of a new procedure by a specialty society: the
      FIBROID registry.
AB  - OBJECTIVE: To describe registry methods and baseline patient demographics from a
      national sample of women undergoing uterine artery embolization for uterine
      leiomyomata. METHODS: Interventional radiology practices were recruited to submit
      data by a secure Web site on women undergoing uterine artery embolization for
      symptomatic leiomyomata. Baseline data included patient demographics, prior
      medical, surgical, and obstetrical history, uterine anatomy, and quality-of-life
      measures. Subsequent data collected included details of the uterine artery
      embolization procedure and hospital stay and outcomes at 30 days; patients were
      also offered the opportunity to participate in longer-term follow-up.
      Characteristics of white and African-American women were compared using t tests,
      chi(2), or Wilcoxon rank-sum tests as appropriate. RESULTS: As of December 31,
      2002, 3,319 uterine artery embolization cases had been entered into the registry
      by 72 sites; number of patients entered by individual sites ranged from 1 to 514.
      Of these patients, 95.4% consented to participation in the short-term outcomes
      registry. Forty-eight percent of patients were African American, and 44.4% were
      white and non-Hispanic. Heavy menstrual bleeding was the single most bothersome
      symptom in 64.3% of patients. Compared with white non-Hispanic women, African
      American women were significantly younger, more likely to be obese, had larger
      uteri and more numerous leiomyomata, more severe symptoms, and poorer quality-of
      life scores before treatment. CONCLUSION: It is feasible to collect prospective
      data on new technologies. The FIBROID Registry prospectively collected data on
      more than 3,000 women undergoing uterine artery embolization for symptomatic
      leiomyomata. Baseline patient characteristics of this patient population seem to
      be similar to those of women undergoing other procedures for leiomyomata. LEVEL
      OF EVIDENCE: III.

PMID- 15994618
TI  - A prospective observational study of domestic violence during pregnancy.
AB  - OBJECTIVE: To assess whether women reporting domestic violence are at increased
      risk for adverse pregnancy outcomes. METHODS: A screening questionnaire,
      previously validated for the identification of female victims of domestic
      violence, was offered to women presenting to our Labor and Delivery Unit. The
      survey prompted women to indicate whether her partner or family member physically
      hurt her, insulted or talked down to her, threatened her with harm, or screamed
      or cursed at her. The primary study outcome was to detect a 3-fold increase in
      low birth weight infants (< or = 2,500 g) in women reporting physical abuse,
      compared with those not reporting domestic violence. RESULTS: A total of 16,041
      women were approached to be interviewed. Of these, 949 (6%) women responded
      affirmatively to one or more of the survey questions, and another 94 (0.6%)
      declined to be interviewed. The incidence of low birth weight infants was
      significantly increased in women who reported verbal abuse, compared with the no
      abuse group (7.6% versus 5.1%, respectively, P = .002). Physical abuse was
      associated with an increased risk of neonatal death (1.5% versus 0.2%, P = .004).
      Interestingly, women who declined to be interviewed had significantly increased
      rates of low birth weight infants (12.8% versus 5.1%, P < .001), preterm birth at
      32 weeks of gestation or less (5.3% versus 1.2%, P = .002), placental abruptions
      (2.1% versus 0.2%, P < .001), and neonatal intensive care admissions (7.4% versus
      2.2%, P = .008) when compared with women in the no-abuse group, respectively.
      CONCLUSION: Women who declined to be surveyed regarding domestic violence were at
      increased risk for adverse pregnancy outcome. LEVEL OF EVIDENCE: II-2.

PMID- 15994617
TI  - The Fibroid Registry for outcomes data (FIBROID) for uterine embolization: short
      term outcomes.
AB  - OBJECTIVE: To investigate the short-term safety of uterine embolization for
      leiomyomata in a large cohort of patients treated in a variety of clinical
      settings. METHODS: Examining the FIBROID Registry, a multicenter prospective
      voluntary registry of patients undergoing uterine embolization for leiomyomata,
      we studied the frequency of adverse events and predictors of adverse events
      within 30 days of the procedure. We also report on the technical aspects of the
      procedure, including details of periprocedural care, technique, and short-term
      recovery. All adverse events were recorded and classified using standard
      definitions, both in terms of type and severity. Summary statistics were used to
      describe the data set, and univariate and multivariate analyses were used to
      determine which factors might influence the incidence of adverse events. RESULTS:
      Of the 3,160 patients enrolled at 72 contributing sites, major in-hospital
      complications occurred in 0.66%, and postdischarge major events occurred in 4.8%
      within the first 30 days. The most common adverse event after discharge was
      inadequate pain relief requiring additional hospital treatment (2.4%). Thirty-one
      patients required additional surgical intervention within 30 days after
      treatment, 3 of whom required hysterectomy (0.1%). There were no deaths.
      Multivariate analysis showed modest increased odds for an adverse event for
      African Americans, smokers, and those with prior leiomyoma procedures. There were
      no differences in outcome based on the practice site experience, practice type,
      or any procedure-related factors. CONCLUSION: Uterine embolization for
      leiomyomata is a low-risk procedure with little variability in short-term outcome
      based on either patient demographics or practice setting. LEVEL OF EVIDENCE: II
      3.

PMID- 15994619
TI  - Racial differences in asthma morbidity during pregnancy.
AB  - OBJECTIVE: Little is known about racial differences in asthma outcomes during
      pregnancy. We performed a cohort study to estimate racial differences in maternal
      asthma outcomes in a low-income population of pregnant women in which blacks and
      whites have similar medical care access and benefits. METHODS: We conducted a
      population-based cohort study of asthma-related morbidity in black and white
      pregnant women enrolled in Tennessee's Medicaid Program, TennCare. Pregnant women
      were identified through TennCare enrollment files linked to birth certificates,
      1995-2001. Prepregnancy, women with asthma were identified using International
      Classification of Diseases, 9th Revision, codes for health care visits and
      pharmacy files for asthma medication. Adjusted relative rates (RR) of rescue
      corticosteroid prescriptions, emergency department (ED) visits, and
      hospitalizations during pregnancy were compared by race using Poisson regression.
      RESULTS: We identified 4,315 women with asthma (4%) from a population of 112,171
      pregnant women of black or white race with at least 180 days of continuous
      enrollment in TennCare before pregnancy. Blacks were more likely to receive a
      course of rescue corticosteroids than whites (14.6% versus 11.9%, adjusted RR
      1.35, 95% confidence interval [CI] 1.14-1.61), have an emergency department visit
      (16.7% versus 8.7%, adjusted RR 1.89, 95% CI 1.57-2.27), or be hospitalized for
      asthma (9.0% versus 5.2%, adjusted RR 1.73, 95% CI 1.34-2.24). CONCLUSION:
      Pregnant women with asthma had high asthma-related morbidity. Black women had
      clinically significantly more morbidity than whites. There is a need to improve
      the medical care of low-income women with asthma, particularly black women. LEVEL
      OF EVIDENCE: II-2.

PMID- 15994620
TI  - Serum C-reactive protein and Chlamydia trachomatis antibodies in preterm
      delivery.
AB  - OBJECTIVE: To assess the association between Chlamydia trachomatis antibodies,
      antibodies to C trachomatis heat shock proteins 60 and 10, and C-reactive protein
      (CRP) levels in maternal serum measured by highly sensitive CRP assay during the
      first trimester and spontaneous preterm delivery before 37 weeks of gestation.
      METHODS: This was a nested case-control study of 104 spontaneous preterm
      singleton deliveries (cases) and 402 term singleton deliveries, as controls, of
      mothers belonging to the population-based Northern Finland 1966 Birth Cohort.
      Data on 2,309 first deliveries were available from the Finnish Medical Birth
      Register. Serum C trachomatis and C pneumoniae antibodies were measured by the
      microimmunofluorescence test and chlamydial heat shock proteins 60 and 10
      antibodies by enzyme immunoassay using recombinant proteins as antigens, and
      highly sensitive CRP levels were quantified with highly sensitive
      immunoenzymometric assay. RESULTS: Highly sensitive CRP levels were higher and C
      trachomatis immunoglobulin G levels (pools and individual serotypes) were more
      often present (thought not nominally significantly in all cases) in the women
      with preterm compared with term deliveries. Elevated immunoglobulin G levels of C
      trachomatis antibodies or elevated highly sensitive CRP levels alone, however,
      did not increase the estimated risk for preterm delivery, but when they were
      present simultaneously, the estimated risk for preterm delivery was 4-fold (odds
      ratio 4.3, 95% confidence interval 2.0-9.3). Among the women delivered at or
      before 34 weeks of gestation, the estimated risk was even more evident (odds
      ratio 5.6, 95% confidence interval 2.1-14.5). The preterm delivery rate was 26.5%
      for those with C trachomatis antibodies and 18.8% for those without C trachomatis
      antibodies. CONCLUSION: The results of the present study suggest that chlamydial
      infection in the first trimester is associated with preterm delivery. LEVEL OF
      EVIDENCE: II-2.

PMID- 15994621
TI  - Adverse perinatal outcomes among interracial couples in the United States.
AB  - OBJECTIVE: We examined the association between parental race and stillbirth and
      adverse perinatal and infant outcomes. METHODS: We conducted a retrospective
      cohort analysis using the 1995-2001 linked birth and infant death files that are
      composed of live births and fetal and infant deaths in the United States. The
      study included singleton births delivered at 20 or more weeks of gestation with a
      fetus weighing 500 g or more (N = 21,005,786). Parental race was categorized as
      mother white-father white, mother white-father black, mother black-father white,
      and mother black-father black. Multivariable logistic regression analysis was
      performed to examine the association between parental race and risks of
      stillbirth (at > or = 20 weeks), small for gestational age (defined as birth
      weight < 5th and < 10th percentile for gestational age), and early neonatal (< 7
      days), late neonatal (7-27 days), and postneonatal (28-364 days) mortality. All
      analyses were adjusted for the confounding effects of maternal age, education,
      trimester at which prenatal care began, parity, marital status, and smoking
      during pregnancy. RESULTS: Although risks varied across parental race categories,
      stillbirth was associated with a higher-than-expected risk for interracial
      couples: mother white-father black, relative risk (RR) 1.17 (95% confidence
      interval [CI] 1.10-1.26) and mother black-father white, RR 1.37 (95% CI 1.21
      1.54) compared with mother white-father white parents. The RR for stillbirth was
      even higher among mother black-father black parents (RR 1.67, 95% CI 1.62-1.72).
      The overall patterns of association for small for gestational age births (< 5th
      and < 10th percentile) and early neonatal mortality were similar to those seen
      for stillbirth. CONCLUSION: There is an increased risk of adverse perinatal
      outcomes for interracial couples, including stillbirth, small for gestational age
      infants, and neonatal mortality. LEVEL OF EVIDENCE: II-2.

PMID- 15994622
TI  - Bleeding patterns after immediate initiation of an oral compared with a vaginal
      hormonal contraceptive.
AB  - OBJECTIVE: This study compared 84-day bleeding patterns after immediate
      initiation of a triphasic oral contraceptive with a 25-mug daily dose of ethinyl
      estradiol (E2) compared with the contraceptive vaginal ring, which has a 15-mug
      daily dose of ethinyl E2. METHODS: This was an open-label controlled trial. We
      randomly assigned 201 women to immediate start of a contraceptive pill or
      immediate start of the ring in a 1:1 allocation ratio. Our primary outcome was
      difference in mean bleeding-spotting days per woman according to treatment
      assignment. Secondary outcomes were differences in World Health Organization
      defined menstrual indices, differences in perceived bleeding changes, and
      differences in bleeding according to cycle day at the start of method. RESULTS:
      The mean bleeding-spotting days in the 84-day reference period for all subjects
      was 19.2 days (17.0 days for ring users and 21.4 days for pill users, mean
      difference 4.4 days). Using the World Health Organization menstrual indices, the
      ring users experienced fewer days or episodes of bleeding-spotting and shorter
      intervals. Among ring users, no baseline characteristics were associated with
      bleeding outcomes. Older nulliparous pill users, however, reported more bleeding
      spotting days. Significantly more ring users reported a decrease in duration of
      bleeding compared with pill users (P < .01). We found no significant differences
      in bleeding patterns based on analysis of cycle day at study enrollment.
      CONCLUSION: Our study shows advantageous bleeding patterns for subjects using the
      contraceptive vaginal ring. It also confirms our previous findings that immediate
      start of hormonal contraception is an acceptable alternative to waiting for
      menses. LEVEL OF EVIDENCE: II-1.

PMID- 15994623
TI  - Oral contraceptives for dysmenorrhea in adolescent girls: a randomized trial.
AB  - OBJECTIVE: To assess whether a low-dose oral contraceptive (OC) is more effective
      than placebo treatment for dysmenorrhea pain in adolescents. METHODS: This was a
      randomized, double-blind, placebo-controlled clinical trial of 76 healthy
      adolescents aged 19 years or younger reporting moderate or severe dysmenorrhea.
      Subjects were randomly allocated to receive either an OC (ethinyl estradiol [E2]
      20 microg and levonorgestrel 100 microg) or a matching placebo for 3 months.
      Participants used their usual pain medications as needed during the trial. The
      main outcome measure was score on the Moos Menstrual Distress Questionnaire (pain
      subscale) for the third menstrual cycle on treatment. Secondary outcomes included
      pain intensity (rated 0 to 10), days of any pain, days of severe pain, hours of
      pain on worst day, and use of pain medications. RESULTS: The mean Moos Menstrual
      Distress Questionnaire pain score was lower (less pain) in the OC group than the
      placebo group (3.1, standard deviation 3.2 compared with 5.8, standard deviation
      4.5, P = .004, 95% confidence interval for the difference between means 0.88
      4.53). By cycle 3, OC users rated their worst pain as less (mean pain rating 3.7
      compared with 5.4, P = .02) and used fewer pain medications than placebo users
      (mean pain pills used 1.3 compared with 3.7, P = .05). By cycle 3, OC users
      reported fewer days of any pain, fewer days of severe pain, and fewer hours of
      pain on the worst pain day than placebo users; however, these differences did not
      reach statistical significance. CONCLUSIONS: Among adolescents, a low-dose oral
      contraceptive relieved dysmenorrhea-associated pain more effectively than
      placebo. LEVEL OF EVIDENCE: I.

PMID- 15994624
TI  - Higher-risk behavioral practices associated with bacterial vaginosis compared
      with vaginal candidiasis.
AB  - OBJECTIVE: Bacterial vaginosis has been associated with hormonal factors and
      sexual practices; however, the cause is unclear, and the notion that bacterial
      vaginosis is a sexually transmitted infection is still debated. To investigate
      whether bacterial vaginosis is associated with specific sexual practices or
      instead has features in common with a sexually transmitted infection, we compared
      behavioral associations in women with bacterial vaginosis to women with vaginal
      candidiasis. METHODS: Women with symptoms of abnormal vaginal discharge or odor
      who attended Melbourne Sexual Health Centre between July 2003 and August 2004
      were eligible for enrollment in the study. Information on demographics and
      behavioral and contraceptive practices were collected by self-completed
      questionnaire. Participants were tested for bacterial vaginosis, Candida spp
      (microscopy and culture), and sexually transmitted infections. Statistical
      comparisons were made between women with and without bacterial vaginosis and
      women with and without candidiasis, using univariate and multivariate analysis.
      RESULTS: A total of 342 women were enrolled in the study; 157 were diagnosed with
      bacterial vaginosis, 51 had candidiasis by microscopy, and 95 had candidiasis by
      culture. Bacterial vaginosis was associated with indicators of high-risk sexual
      behavior such as a new sexual partner and greater number of male partners in the
      last year, increased number of lifetime sexual partners, less than 13 years of
      education, a past history of pregnancy, and smoking (P < .05). Candidiasis was
      not associated with these risk behaviors and was instead related to practices
      such as receptive anal and oral sex and douching. CONCLUSION: The association
      between bacterial vaginosis and practices that are associated with sexually
      transmitted infections, in contrast to those observed with candidiasis, suggests
      a possible sexually transmitted cause. LEVEL OF EVIDENCE: II-2.

PMID- 15994625
TI  - Cervical dysplasia in adolescents.
AB  - BACKGROUND: Although the incidence of cervical dysplasia in adolescents is
      increasing, a paucity of data exists regarding the outcomes of adolescents with
      Pap test abnormalities. We determined the natural history and outcome of
      adolescents with low-grade squamous intraepithelial lesions (LSIL) and high-grade
      squamous intraepithelial lesions (HSIL). METHODS: A review of all women aged 18
      years or younger with a cytologic diagnosis of LSIL or HSIL between 1997 and 2003
      was performed. Follow-up cytologic and histologic samples were evaluated. The
      most significant abnormality was recorded for each patient. Rates of regression,
      persistence, and progression were calculated. RESULTS: A total of 646 adolescents
      were identified. Follow-up was available for 477 teenagers with LSIL and for 55
      with HSIL. Among adolescents with LSIL, 146 (35%) had negative follow-up. Low
      grade abnormalities (atypical squamous cells of undetermined significance, LSIL,
      and cervical intraepithelial neoplasia grade 1) were seen in 199 (47%), whereas
      high-grade abnormalities were documented in 77 (18%). After 36 months, 62% had
      regressed, whereas 31% had progressive dysplasia. For the HSIL cohort, negative
      follow-up was documented in 12 (21.8%) adolescents, and 15 (27.3%) had low-grade
      abnormalities, whereas more than one half (50.9%) were found to have a high-grade
      abnormality. At 36 months, 31% of HSIL subjects had progressed to cervical
      intraepithelial neoplasia 3. CONCLUSION: Adolescents with LSIL and HSIL cytology
      are at significant risk for progression to high-grade cervical abnormalities. The
      rate of development of high-grade cervical abnormalities in adolescents is
      similar to adults. Adolescents with cytologic abnormalities mandate close follow
      up. LEVEL OF EVIDENCE: II-3.

PMID- 15994626
TI  - Sexual activity and function in postmenopausal women with heart disease.
AB  - OBJECTIVE: To examine the prevalence and correlates of sexual activity and
      function in postmenopausal women with heart disease. METHODS: We included
      baseline self-reported measures of sexual activity and the sexual problem scale
      from the Medical Outcomes Study in the Heart and Estrogen/Progestin Replacement
      Study (HERS), a study of 2,763 postmenopausal women, average age 67 years, with
      coronary disease and intact uteri. We used multivariable linear and logistic
      regression to identify independent correlates of sexual activity and dysfunction.
      RESULTS: Approximately 39% of the women in HERS were sexually active, and 65% of
      these reported at least 1 of 5 sexual problems (lack of interest, inability to
      relax, difficulty in arousal or in orgasm, and discomfort with sex). In
      multivariable analysis, factors independently associated with being sexually
      active included younger age, fewer years since menopause, being married, better
      self-reported health, higher parity, moderate alcohol use, not smoking, lack of
      chest discomfort, and not being depressed. Among the 1,091 women who were
      sexually active, lower sexual problem scores were associated with being
      unmarried, being better educated, having better self-reported health, and having
      higher body mass index. CONCLUSION: Many women with heart disease continue to
      engage in sexual activity into their 70s, and two thirds of these report
      discomfort and other sexual function problems. Physicians should be aware that
      postmenopausal patients are sexually active and address the problems these women
      experience. LEVEL OF EVIDENCE: II-2.

PMID- 15994627
TI  - Topical analgesia for endometrial biopsy: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether benzocaine spray applied to the cervix and the
      endocervical canal before performing office endometrial biopsy improves patient
      comfort during the procedure. METHODS: Eighty-eight women were randomly assigned
      to receive either 20% benzocaine spray or placebo to the outside of the cervix
      and into the endocervical canal before an endometrial biopsy was performed. The
      main outcome measure was pain during the endometrial biopsy, assessed by a visual
      analog scale. Statistical analysis was performed using Wilcoxon rank-sum test and
      Student t test. RESULTS: There were no statistically significant differences
      between the study group and the control group in mean age, race, parity, body
      mass index, menopausal status, tenaculum use, or history of chronic pelvic pain.
      No statistically significant differences were found in median pain scores between
      the 2 treatment groups. CONCLUSION: Topical benzocaine spray does not appear to
      offer effective pain control in patients undergoing an endometrial biopsy. LEVEL
      OF EVIDENCE: I.

PMID- 15994628
TI  - Screening women with polycystic ovary syndrome for metabolic syndrome.
AB  - OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are at an increased risk
      for insulin resistance and hyperlipidemia. Metabolic syndrome is a cluster of
      risk factors that confers an increased risk for cardiovascular disease. The
      objectives of this study were to compare the prevalence of metabolic syndrome in
      women with PCOS and controls and to identify the role of androgens or insulin
      resistance in the development of metabolic syndrome. METHODS: Women with PCOS (n
      = 129) and women with regular menses and no hirsutism seen for an annual
      examination (n = 177) were studied. RESULTS: The age-adjusted prevalence of
      metabolic syndrome was higher in women with PCOS (47.3%, 95% confidence interval
      35.3-56.9%) compared with controls (4.3%, 95% confidence interval 1.9-7.6%, P <
      .001). Compared by age group, the risk of metabolic syndrome in women with PCOS
      was higher for all groups (P < .001). There were no significant differences in
      serum androgen levels between women with PCOS with or without metabolic syndrome.
      In contrast, all markers of insulin resistance were abnormal in women with PCOS
      with metabolic syndrome compared with those without metabolic syndrome (P <
      .001). We found serum triglyceride/high density lipoprotein cholesterol (TG/HDL
      C) ratio correlated with insulin resistance in this population (P < .001). Serum
      TG/HDL-C > 3.2 has a high sensitivity and specificity for the detection of
      metabolic syndrome in women with PCOS. CONCLUSION: Women with PCOS have a 11-fold
      increase in the prevalence of metabolic syndrome compared with age-matched
      controls. The risk of metabolic syndrome is high even at a young age,
      highlighting the importance of early and regular screening. The TG/HDL-C ratio
      may serve as a screening tool and needs to be prospectively validated in this
      group. LEVEL OF EVIDENCE: II-2.

PMID- 15994629
TI  - Acupuncture for overactive bladder: a randomized controlled trial.
AB  - OBJECTIVE: To compare acupuncture treatment for overactive bladder with urge
      incontinence with a placebo acupuncture treatment. METHODS: Eighty-five women
      enrolled in this randomized, placebo-controlled trial. Women were randomly
      assigned to either receive an acupuncture treatment expected to improve their
      bladder symptoms, or a placebo acupuncture treatment designed to promote
      relaxation. They underwent cystometric testing, completed a 3-day voiding diary,
      and completed the urinary distress inventory and incontinence impact
      questionnaire, validated quality-of-life inventories, before and after 4 weekly
      acupuncture treatments. The primary endpoint was number of incontinent episodes
      over 3 days. Secondary endpoints included voiding frequency and urgency,
      cystometric bladder capacity, maximum voided volume, and the urinary distress
      inventory and incontinence impact questionnaire symptom scores. RESULTS: Seventy
      four women completed all aspects of the study. Women in both treatment and
      placebo groups had significant decreases in number of incontinent episodes (59%
      for treatment, 40% for placebo) without a significant difference in the change
      between the groups. Women in the treatment group had a 14% reduction in urinary
      frequency (P = .013), a 30% reduction in the proportion of voids associated with
      urgency (P = .016), and a 13% increase in both maximum voided volume and maximum
      cystometric capacity (P = .01). Both groups also had an improvement in the
      urinary distress inventory and incontinence impact questionnaire scores (54%
      decrease for treatment, 30% decrease for placebo, P < .001 for the difference in
      change between the groups). CONCLUSION: Women who received 4 weekly bladder
      specific acupuncture treatments had significant improvements in bladder capacity,
      urgency, frequency, and quality-of-life scores as compared with women who
      received placebo acupuncture treatments. LEVEL OF EVIDENCE: I.

PMID- 15994630
TI  - Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia.
AB  - OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved
      in placental and fetal growth. We examined whether the concentration of ADAM12 in
      first-trimester maternal serum could be used as a marker for preeclampsia.
      METHODS: We developed a semiautomated, time-resolved, immunofluorometric assay
      for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range
      of 78-1248 microg/L. Serum samples derived from women in the first trimester of a
      normal pregnancy (n = 324) and from women who later developed preeclampsia during
      pregnancy (n = 160) were obtained from the First Trimester Copenhagen Study.
      ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were
      converted to multiples of the median (MoM) after log-linear regression of
      concentration versus gestational age. RESULTS: Serum ADAM12 levels in women who
      developed preeclampsia during pregnancy had a mean log MoM of -0.066, which was
      significantly lower than the mean log MoM of -0.001 for ADAM12 levels observed in
      serum samples from women with normal pregnancy (P = .008). The mean log MoM was
      even lower in serum derived from preeclamptic women whose infant's weight at
      birth was less than 2,500 g (n = 27, mean log MoM of -0.120, P = .053).
      CONCLUSION: The maternal serum levels of ADAM12 are significantly lower during
      the first trimester in women who later develop preeclampsia during pregnancy when
      compared with levels in women with normal pregnancies. Because the secreted form
      of ADAM12 cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP
      5, the IGF axis may play a role in preeclampsia. ADAM12 may be a useful early
      marker for preeclampsia. LEVEL OF EVIDENCE: II-2.

PMID- 15994631
TI  - Cesarean delivery in the United Kingdom: time trends in the general practice
      research database.
AB  - OBJECTIVE: To estimate recent temporal trends in delivery by cesarean during the
      past decade and the proportion of vaginal deliveries after prior caesarean in the
      United Kingdom. METHODS: We conducted a cohort study using information from the
      General Practice Research Database. We identified all women with 1 or more
      deliveries between January 1990 and December 1999 and determined the method(s) of
      delivery. We estimated the proportion of women with vaginal delivery after
      cesarean in a subcohort who had at least 3 years of follow-up. RESULTS: We
      identified 39,938 cesareans among 271,663 deliveries (14.7%), with an increase
      from 12.5% in 1990 to 18.3% in 1999. The proportion of cesarean deliveries
      increased with age and increased over time in all age groups except women aged
      younger than 20 years. Among 26,480 women with a caesarean delivery between 1990
      and 1996, 7,649 (28.9%) had a subsequent delivery. The proportion of vaginal
      delivery after prior cesarean decreased from 45% in 1991 to 37% in 1999.
      CONCLUSION: Cesarean deliveries increased as a proportion of all deliveries in
      the United Kingdom during the past decade, and the proportion of vaginal delivery
      after prior cesarean decreased. Still, the proportion of cesarean deliveries is
      lower and the proportion of vaginal deliveries after prior cesarean is higher in
      the United Kingdom than in the United States. LEVEL OF EVIDENCE: II-2.

PMID- 15994632
TI  - Maternal ethnicity, paternal ethnicity, and parental ethnic discordance:
      predictors of preeclampsia.
AB  - OBJECTIVE: To examine the association of maternal and paternal ethnicity as well
      as parental ethnic discordance with preeclampsia. METHODS: Retrospective cohort
      study of all low-risk women delivered from 1995 to 1999 within a mature managed
      care organization. Rates of preeclampsia were calculated for maternal, paternal,
      and combined ethnicity using both univariate and multivariate analyses. RESULTS:
      Among the 127,544 low-risk women, when examining maternal ethnicity in a
      multivariate model controlling for maternal age, parity, education, and
      gestational age, we found that the rates of preeclampsia were higher among
      African American (5.2%; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.25
      1.62) women and lower among Latina (4.0%; OR 0.90, 95% CI 0.84-0.97) and Asian
      women (3.5%; OR 0.79, 95% CI 0.72-0.88), with all results being statistically
      significant as compared with white women. When paternal ethnicity was controlled
      for separately, however, the difference in the rate of preeclampsia among Asian
      women disappeared, the effect of African-American maternal ethnicity increased
      slightly (OR 1.49, 95% CI 1.33-1.72), and Asian paternity was found to be
      associated with the lowest rate of preeclampsia (3.2%; OR 0.76, 95% CI 0.68
      0.85). Further, parental ethnic discordance was associated with an increase in
      the rate of preeclampsia (OR 1.13, 95% CI 1.02 - 1.26). CONCLUSION: We found that
      rates of preeclampsia were lower with Asian paternal ethnicity. We also found
      that having a differing paternal and maternal ethnicity was associated with
      increased rates of preeclampsia. For every 1,000 pregnancies, there would be
      approximately 10 fewer cases of preeclampsia in the setting of Asian paternity
      and 5 more cases of preeclampsia in the setting of parental ethnic discordance.
      These differences may be useful in further investigation of the cause of
      preeclampsia. LEVEL OF EVIDENCE: II-2.

PMID- 15994633
TI  - Immunogenetic determinants of preeclampsia and related pregnancy disorders: a
      systematic review.
AB  - OBJECTIVE: We sought to systematically review the impact of immunogenetic
      factors, specifically human leukocyte antigen (HLA) allele frequencies, maternal
      homozygosity, couple sharing, and maternal-fetal sharing, on the risk of
      preeclampsia and intrauterine growth restriction. DATA SOURCES: A computerized
      search of PubMed databases from 1975 to 2003 was performed with the terms
      "preeclampsia," "eclampsia," "intrauterine growth restriction," and "human
      leukocyte antigens" and limited to studies of human subjects in English. No
      restrictions were placed on study design. All bibliographies were cross
      referenced to identify additional pertinent studies. METHODS OF STUDY SELECTION:
      Titles and abstracts were reviewed carefully. Observational and basic science
      research studies were selected if their main objective was to assess the
      relationship of any aspect of HLA genotypes with preeclampsia and related
      disorders of pregnancy. TABULATION, INTEGRATION, AND RESULTS: Data were
      abstracted and tabulated from 22 original research studies. Meta-analytic
      techniques were not performed owing to variations in disease and exposure
      definitions as well as research methodologies. Studies that examined maternal,
      paternal, and fetal HLA allele frequencies, maternal homozygosity, and couple
      sharing yielded inconsistent results. Although the cumulative evidence points to
      the HLA-DR locus (particularly DR4) as a correlate of preeclampsia, it remains
      unclear whether any specific HLA allele, haplotype, or susceptibility gene in
      linkage disequilibrium with the HLA region is responsible. Although genetic
      evidence is suggestive of gene-gene interaction between mother and fetus, few
      studies have evaluated the influence of maternal-fetal HLA sharing. CONCLUSION:
      In the early 1990s, HLA genotypes were dismissed as possible etiologic factors
      for preeclampsia, based on studies that are heterogeneous with respect to study
      design, outcome, and exposure assessment. Many of these studies did not take into
      account the interactions between maternal, paternal, and infant genotypes. Thus,
      adequately powered studies designed specifically to assess the effect of maternal
      fetal HLA sharing on risk of preeclampsia are needed.

PMID- 15994634
TI  - Assessing the neonatal safety of indomethacin tocolysis: a systematic review with
      meta-analysis.
AB  - OBJECTIVE: To systematically review and summarize the medical literature
      regarding the effects of tocolysis with indomethacin on neonatal outcome. DATA
      SOURCES: We supplemented a search of entries in electronic databases with
      references cited in original studies and review articles to identify studies
      pertaining to indomethacin tocolysis and neonatal outcome. METHODS OF STUDY
      SELECTION: We evaluated, abstracted data, and performed quantitative analyses in
      studies assessing the neonatal outcomes of patients undergoing tocolysis with
      indomethacin. Observational studies and randomized trials were included in this
      systematic review. TABULATION, INTEGRATION, AND RESULTS: Forty-six studies were
      identified, 28 of which met criteria for systematic review and meta-analysis.
      These 28 studies included 6,008 infants. Of these infants, 1,621 were exposed to
      indomethacin for tocolysis antenatally; 4,387 infants not exposed to indomethacin
      served as the comparison group. An estimate of pooled odds ratios with 95%
      confidence intervals was calculated for dichotomous outcomes using random- and
      fixed-effects models. Observational studies and randomized trials were analyzed
      separately. Pooled estimates from observational studies and randomized trials
      revealed no significant differences in the rates of intraventricular hemorrhage,
      patent ductus arteriosus, necrotizing enterocolitis, or neonatal mortality
      between infants exposed to indomethacin antenatally and those not exposed. Meta
      analysis of randomized trials revealed increased risk of bronchopulmonary
      dysplasia. However, the meta-analysis included only 3 randomized clinical trials,
      one of which showed increased risk. An association of bronchopulmonary dysplasia
      and indomethacin use was not noted in our analysis of observational studies.
      CONCLUSION: Although our pooled results did not identify significantly increased
      risks of adverse effects, the limited statistical power of published randomized
      trials does not allow us to exclude the possibility that indomethacin tocolysis
      increases the risk of adverse neonatal outcomes.

PMID- 15994635
TI  - Cerclage for short cervix on ultrasonography: meta-analysis of trials using
      individual patient-level data.
AB  - OBJECTIVE: Preterm birth is the main cause of perinatal morbidity and mortality.
      A short cervical length on transvaginal ultrasonography predicts preterm birth.
      Our aim was to estimate by meta-analysis of randomized trials whether cerclage
      prevents preterm birth in women with a short cervical length. DATA SOURCES:
      MEDLINE, PubMed, EMBASE, and the Cochrane Library were searched with the terms
      "cerclage," "cervical cerclage," "short cervix," "ultrasound," and "randomized
      trial." We included randomized trials involving the use of cerclage in women with
      short cervical length on transvaginal ultrasonography using patient-level data.
      TABULATION, INTEGRATION, AND RESULTS: Four properly conducted trials were
      identified. In the total population, preterm birth at less than 35 weeks of
      gestation occurred in 29.2% (89/305) of the cerclage group, compared with 34.8%
      (105/302) of the no-cerclage groups (relative risk [RR] 0.84, 95% confidence
      interval [CI] 0.67-1.06). There was no significant heterogeneity in the overall
      analysis (P = .29). There was a significant reduction in preterm birth at less
      than 35 weeks in the cerclage group compared with the no-cerclage groups in
      singleton gestations (RR 0.74, 95% CI 0.57-0.96), singleton gestations with prior
      preterm birth (RR 0.61, 95% CI 0.40-0.92), and singleton gestations with prior
      second-trimester loss (RR 0.57, 95% CI 0.33-0.99). There was a significant
      increase in preterm birth at less than 35 weeks in twin gestations (RR 2.15, 95%
      CI 1.15-4.01). CONCLUSION: Cerclage does not prevent preterm birth in all women
      with short cervical length on transvaginal ultrasonography. In the subgroup
      analysis of singleton gestations with short cervical length, especially those
      with a prior preterm birth, cerclage may reduce preterm birth, and a well-powered
      trial should be carried out in this group of patients. In contrast, in twins,
      cerclage was associated with a significantly higher incidence of preterm birth.

PMID- 15994636
TI  - What's a cervix?

PMID- 15994645
TI  - Pregnancy after uterine artery embolization for leiomyomata: the Ontario
      Multicenter Trial.

PMID- 15994647
TI  - Abdominal pain, bloating, and urgency.

PMID- 15994648
TI  - Use of follicle-stimulating hormone test to predict poor response in in vitro
      fertilization.

PMID- 15994651
TI  - Racial differences in cesareans: an analysis of U.S. 2001 National Inpatient
      Sample data.

PMID- 15994654
TI  - Subclinical hypothyroidism and pregnancy outcomes.

PMID- 15994656
TI  - Effect of gestational age and position on peak expiratory flow rate: a
      longitudinal study.

PMID- 15994657
TI  - ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician
      Gynecologists Number 64, July 2005 (Replaces Committee Opinion Number 238, July
      2000): hemoglobinpathies in pregnancy.
AB  - The hemoglobinopathies are a heterogeneous group of single-gene disorders that
      include the structural hemoglobin variants and the thalassemias. More than 270
      million people worldwide are heterozygous carriers of hereditary disorders of
      hemoglobin, and at least 300,000 affected homozygotes or compound heterozygotes
      are born each year (1). The purpose of this document is to review the most common
      hemoglobinopathies and to provide recommendations for the screening and clinical
      management of hemoglobinopathies during pregnancy.

PMID- 15994658
TI  - Intermediate care: policy before evidence.

PMID- 15994659
TI  - Treatment of ocular hypertension and open angle glaucoma: meta-analysis of
      randomised controlled trials.
AB  - OBJECTIVE: Open angle glaucoma is one of the most common causes of blindness in
      industrialised nations. Treatments to lower ocular pressure are widely used in
      glaucoma prevention and treatment, despite conflicting evidence. DESIGN: We
      performed meta-analyses to reassess the effectiveness of pressure lowering
      treatment to delay the development of glaucoma in ocular hypertension, as well as
      progression of manifest open angle glaucoma. DATA SOURCES: Medline, Embase, and
      the Cochrane Library. SELECTION OF STUDIES: Eligible studies were randomised
      controlled trials with a concurrent untreated control group and information on
      time to glaucomatous changes to visual field and optic disc. Trial reports were
      reviewed independently by two investigators in an unblinded standardised manner.
      RESULTS: Meta-analysis of trials in ocular hypertension showed a significant
      preventive effect of reducing intraocular pressure on progression to glaucoma
      (hazard ratio 0.56, 95% confidence interval 0.39 to 0.81, P = 0.01; number needed
      to treat 12). Pooled data of studies in manifest glaucoma showed a significant
      delay of visual field deterioration (0.65, 0.49 to 0.87, P = 0.003; NNT = 7),
      with subgroup analysis showing a larger effect in patients with raised pressure
      and a reduced effect in normal tension glaucoma (subgroup comparison: not
      significant). CONCLUSIONS: Lowering intraocular pressure in patients with ocular
      hypertension or manifest glaucoma is beneficial in reducing the risk of visual
      field loss in the long term.

PMID- 15994661
TI  - The future of health care in Africa.

PMID- 15994660
TI  - Effects of locality based community hospital care on independence in older people
      needing rehabilitation: randomised controlled trial.
AB  - OBJECTIVE: To determine the effects on independence in older people needing
      rehabilitation in a locality based community hospital compared with care on a
      ward for elderly people in a district general hospital. DESIGN: Randomised
      controlled trial. SETTING: Care in a community hospital and district general
      hospital in Bradford, England. PARTICIPANTS: 220 patients needing rehabilitation
      after an acute illness that required hospital admission. INTERVENTIONS: Patients
      were randomly allocated to a locality based community hospital or to remain
      within a department for the care of elderly people in a district general
      hospital. MAIN OUTCOME MEASURES: Primary outcomes were Nottingham extended
      activities of daily living scale and general health questionnaire 28 (carer).
      Secondary outcomes were activities of daily living (Barthel index), Nottingham
      health profile, hospital anxiety and depression scale, mortality, destination
      after discharge, satisfaction with services, carer strain index, and carer's
      satisfaction with services. RESULTS: The median length of stay was 15 days for
      both the community hospital and the district general hospital groups
      (interquartile range: community hospital 9-25 days; district general hospital 9
      24 days). Independence at six months was greater in the community hospital group
      (adjusted mean difference 5.30, 95% confidence interval 0.64 to 9.96). Results
      for the secondary outcome measures, including care satisfaction and measures of
      carer burden, were similar for both groups. CONCLUSIONS: Care in a locality based
      community hospital is associated with greater independence for older people than
      care in wards for elderly people in a district general hospital.

PMID- 15994662
TI  - Stopping Africa's medical brain drain.

PMID- 15994663
TI  - Do white British children and adolescents get enough sunlight?

PMID- 15994664
TI  - Drug safety and regulation.

PMID- 15994665
TI  - Attempts to prevent postnatal depression.

PMID- 15994666
TI  - American Medical Association rejects proposal to ban consumer adverts for
      prescription medicines.

PMID- 15994667
TI  - Poorer countries will not meet health targets, warns WHO.

PMID- 15994669
TI  - Israeli doctors want to stop European patent for genetic test.

PMID- 15994671
TI  - Doctors to consider scrubs to reduce infection.

PMID- 15994673
TI  - Campaign to deliver AIDS drugs to 3 million will miss end of year target.

PMID- 15994676
TI  - Cancer guidelines from NICE aim to reduce variation in referral times.

PMID- 15994677
TI  - Use of antiviral drug in poultry is blamed for drug resistant strains of avian
      flu.

PMID- 15994678
TI  - American Medical Association fights pharmacists who won't dispense
      contraceptives.

PMID- 15994680
TI  - Developing countries may not get benefits of GM food.

PMID- 15994686
TI  - Further action taken on COX 2 inhibitors in Europe.

PMID- 15994687
TI  - Prioritising neglected diseases related to poverty.

PMID- 15994689
TI  - Management and referral for trigger finger/thumb.

PMID- 15994690
TI  - ABC of conflict and disaster. The special needs of children and women.

PMID- 15994688
TI  - Psychosocial and psychological interventions for prevention of postnatal
      depression: systematic review.
AB  - OBJECTIVE: To assess the effects of psychosocial and psychological interventions
      compared with usual antepartum, intrapartum, or postpartum care on the risk of
      postnatal depression. DATA SOURCES: Medline, Embase, CINAHL, Cochrane central
      register of controlled trials, Cochrane pregnancy and childbirth group trials
      register, Cochrane depression, anxiety, and neurosis trials register, secondary
      references and review articles, and experts in the field. STUDY SELECTION: All
      published and unpublished randomised controlled trials of preventive psychosocial
      or psychological interventions in which the primary or secondary aim was a
      reduction in the risk of postnatal depression. All trials recruited pregnant
      women or new mothers less than six weeks postpartum. Eligible studies were
      abstracted, assessed for methodological quality, and pooled with relative risk
      for categorical data and weighted mean difference for continuous data. RESULTS:
      Fifteen trials with 7697 women were included. Although there was no overall
      statistically significant effect on the prevention of postnatal depression in the
      meta-analysis of all types of interventions (15 trials, n = 7697; relative risk
      0.81, 95% confidence interval 0.65 to 1.02), these results suggest a potential
      reduction in postnatal depression. The only intervention to have a clear
      preventive effect was intensive postpartum support provided by a health
      professional (0.68, 0.55 to 0.84). Identifying women "at risk" assisted in the
      prevention of postnatal depression (0.67, 0.51 to 0.89). Interventions with only
      a postnatal component were more beneficial (0.76, 0.58 to 0.98) than
      interventions that incorporated an antenatal component. In addition, individually
      based interventions were more effective (0.76, 0.59 to 1.00) than group based
      interventions (1.03, 0.65 to 1.63). CONCLUSIONS: Diverse psychosocial or
      psychological interventions do not significantly reduce the number of women who
      develop postnatal depression. The most promising intervention is the provision of
      intensive, professionally based postpartum support.

PMID- 15994691
TI  - Effect of globalisation on children's mental health.

PMID- 15994692
TI  - Global consumption and the challenge to pharmaceutical governance in the United
      Kingdom.

PMID- 15994693
TI  - Managing medical migration from poor countries.

PMID- 15994694
TI  - Open letter to Tony Blair on publication of the report of the Commission for
      Africa.

PMID- 15994695
TI  - Developed world is robbing Africa of health staff: there are no easy answers.

PMID- 15994696
TI  - Developed world is robbing Africa of health staff: new ways of delivering health
      care are needed in developing countries.

PMID- 15994697
TI  - A farewell to alms.

PMID- 15994698
TI  - Aid after disasters: economic considerations tend to take priority.

PMID- 15994699
TI  - Damage v ability to cope shapes need for disaster aid.

PMID- 15994700
TI  - Developed world is robbing Africa of health staff: health of nations needs more
      than health professionals.

PMID- 15994701
TI  - Coping with the aftermath of trauma: NICE guidelines on post-traumatic stress
      disorder have fundamental flaw.

PMID- 15994702
TI  - Aid after disasters: evidence for psychosocial services needs strengthening.

PMID- 15994703
TI  - Are depression and bipolar disorder the same illness?

PMID- 15994704
TI  - "A gene for...": the nature of gene action in psychiatric disorders.
AB  - A central phrase in the new "GeneTalk" is "X is a gene for Y," in which X is a
      particular gene on the human genome and Y is a complex human disorder or trait.
      This article begins by sketching the historical origins of this phrase and the
      concept of the gene-phenotype relationship that underlies it. Five criteria are
      then proposed to evaluate the appropriateness of the "X is a gene for Y" concept:
      1) strength of association, 2) specificity of relationship, 3) noncontingency of
      effect, 4) causal proximity of X to Y, and 5) the degree to which X is the
      appropriate level of explanation for Y. Evidence from psychiatric genetics is
      then reviewed that address each of these criteria. The concept of "a gene for..."
      is best understood as deriving from preformationist developmental theory in which
      genes-like preformationist anlagen-"code for" traits in a simple, direct, and
      powerful way. However, the genetic contribution to psychiatric disorders fails to
      meet any of the five criteria for the concept of "X is a gene for Y." The impact
      of individual genes on risk for psychiatric illness is small, often nonspecific,
      and embedded in complex causal pathways. The phrase "a gene for..." and the
      preformationist concept of gene action that underlies it are inappropriate for
      psychiatric disorders.

PMID- 15994705
TI  - The cerebellum.

PMID- 15994707
TI  - Structural brain magnetic resonance imaging of limbic and thalamic volumes in
      pediatric bipolar disorder.
AB  - BACKGROUND: Youths with bipolar disorder are ideal for studying illness
      pathophysiology given their early presentation, lack of extended treatment, and
      high genetic loading. Adult bipolar disorder MRI studies have focused
      increasingly on limbic structures and the thalamus because of their role in mood
      and cognition. On the basis of adult studies, the authors hypothesized a priori
      that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic
      volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV
      bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12
      male, eight female) similar in age and sex underwent structured and clinical
      interviews, neurological examination, and cognitive testing. Differences in
      limbic and thalamic brain volumes, on the logarithmic scale, were tested using a
      two-way (diagnosis and sex) univariate analysis of variance, with total cerebral
      volume and age controlled. RESULTS: The subjects with bipolar disorder had
      smaller hippocampal volumes. Further analysis revealed that this effect was
      driven predominantly by the female bipolar disorder subjects. In addition, both
      male and female youths with bipolar disorder had significantly smaller cerebral
      volumes. No significant hemispheric effects were seen. CONCLUSIONS: These
      findings support the hypothesis that the limbic system, in particular the
      hippocampus, may be involved in the pathophysiology of pediatric bipolar
      disorder. While this report may represent the largest MRI study of pediatric
      bipolar disorder to date, more work is needed to confirm these findings and to
      determine if they are unique to pediatric bipolar disorder.

PMID- 15994708
TI  - Familial variation in episode frequency in bipolar affective disorder.
AB  - OBJECTIVE: Bipolar affective disorder is a familial illness characterized by
      recurrent episodes of mania and depression, but little is known about the
      familial nature of episode recurrence or its associated clinical features. The
      authors analyzed the recurrence frequency of affective episodes (episode
      frequency), along with associated clinical and demographic variables, in families
      with at least three members with a major affective disorder. METHOD: Members of
      86 families ascertained through probands with bipolar affective disorder who had
      two or more first-degree relatives with a major affective disorder were
      interviewed by psychiatrists and assigned an all-sources diagnosis. Data for 407
      subjects with a major affective disorder were analyzed. Episode frequency was
      estimated as the number of episodes of major depression, mania, and hypomania per
      year of illness. RESULTS: Episode frequency was smoothly distributed over the
      range of 0.02-20.2 episodes/year. Episode frequency was significantly correlated
      among relatives (r=0.56, p<0.004). Earlier age at onset, bipolar II disorder,
      hallucinations or delusions, alcoholism, and suicidal behavior were all more
      prevalent in the highest than in the lowest quartiles of episode frequency.
      Female gender and recurrent major depression were more prevalent in the lowest
      quartile. Panic disorder, substance abuse, and thyroid disease were all unrelated
      to episode frequency. Subjects with DSM-IV rapid cycling did not differ from
      other affected subjects for most of the variables tested. CONCLUSIONS: Episode
      frequency is a highly familial trait in bipolar affective disorder, associated
      with several indicators of severity, and may be useful in defining clinical
      subtypes of bipolar affective disorder with greater genetic liability. DSM-IV
      rapid cycling was not supported by these data as the best predictor of
      familiality or severity.

PMID- 15994709
TI  - Comparison of rapid-cycling and non-rapid-cycling bipolar disorder based on
      prospective mood ratings in 539 outpatients.
AB  - OBJECTIVE: To detect risk factors for rapid cycling in bipolar disorder, the
      authors compared characteristics of rapid-cycling and non-rapid-cycling patients
      both from a categorical and a dimensional perspective. METHOD: Outpatients with
      bipolar I disorder (N=419), bipolar II disorder (N=104), and bipolar disorder not
      otherwise specified (N=16) were prospectively evaluated with daily mood ratings
      for 1 year. Subjects were classified as having rapid cycling (defined by the DSM
      IV criterion of four or more manic or depressive episodes within 1 year) or not
      having rapid cycling, and the two groups' demographic and retrospective and
      prospective illness characteristics were compared. Associated factors were also
      evaluated in relationship to episode frequency. RESULTS: Patients with rapid
      cycling (N=206; 38.2%) significantly differed from those without rapid cycling
      (N=333) with respect to the following independent variables: history of childhood
      physical and/or sexual abuse, bipolar I disorder subtype, number of lifetime
      manic or depressive episodes, history of rapid cycling, and history of drug
      abuse. The prevalence of these characteristics increased progressively with
      episode frequency. The proportion of women was greater than the proportion of men
      only among patients with eight or more episodes per year. The average time spent
      manic/hypomanic increased as a function of episode frequency, but the average
      time spent depressed was comparable in patients with one episode and in those
      with more than one episode. Brief episodes were as frequent as full-duration DSM
      IV-defined episodes. CONCLUSIONS: A number of heterogeneous risk factors were
      progressively associated with increasing episode frequency. Depression
      predominated in all bipolar disorder patients, but patients with rapid cycling
      were more likely to be characterized by manic features. The findings overall
      suggest that rapid cycling is a dimensional course specifier arbitrarily defined
      on a continuum of episode frequency.

PMID- 15994710
TI  - Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12
      month, randomized, double-blind, controlled clinical trial.
AB  - OBJECTIVE: The authors compared the efficacy of olanzapine and lithium in the
      prevention of mood episode relapse/recurrence. METHOD: Patients with a diagnosis
      of bipolar disorder (manic/mixed), a history of two or more manic or mixed
      episodes within 6 years, and a Young Mania Rating Scale total score > or =20
      entered the study and received open-label co-treatment with olanzapine and
      lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania
      Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8)
      were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5
      20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214).
      RESULTS: Symptomatic relapse/recurrence (score > or =15 on either the Young Mania
      Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine
      treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine
      relative to lithium (primary objective) in preventing relapse/recurrence was met,
      since the lower limit of the 95% confidence interval on the 8.8% risk difference
      (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary
      results showed that compared with lithium, olanzapine had significantly lower
      risks of manic episode and mixed episode relapse/recurrence. Depression
      relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium
      treated patients. Mean weight gain during open-label co-treatment was 2.7 kg;
      during double-blind monotherapy, weight gain was significantly greater with
      olanzapine (1.8 kg) than with lithium (-1.4 kg). CONCLUSIONS: These results
      suggest that olanzapine was significantly more effective than lithium in
      preventing manic and mixed episode relapse/recurrence in patients acutely
      stabilized with olanzapine and lithium co-treatment. Both agents were comparable
      in preventing depression relapse/recurrence.

PMID- 15994711
TI  - Service use and outcomes of first-admission patients with psychotic disorders in
      the Suffolk County Mental Health Project.
AB  - OBJECTIVE: The purpose of the study was to examine the inpatient and outpatient
      service use and 4-year outcomes of newly admitted psychotic patients during a
      period of rapid change in the provision of psychiatric services in a well-defined
      catchment area in New York State in the 1990s. METHOD: Subjects were 573
      participants of the Suffolk County Mental Health Project. This group comprised
      patients with psychotic disorders first admitted between September 1989 and
      August 1995 to 12 inpatient facilities across Suffolk County, N.Y., and followed
      for up to 48 months. The subjects' service use, course of illness, symptomatic
      outcomes, suicide risk, homelessness risk, and satisfaction with care were
      compared across admission years. RESULTS: The length of inpatient stays decreased
      significantly across the years. However, the number of outpatient visits and
      therapy sessions did not vary. Although the patients admitted in later years were
      more symptomatic at admission to their first hospitalization, their course and
      outcomes over the follow-up period were not worse and they were not less
      satisfied with their care, compared with the patients admitted in earlier years.
      CONCLUSIONS: The clinical characteristics of patients and the role of inpatient
      care in the management of patients with psychotic disorders gradually changed
      during the 1990s. These changes, however, were not associated with changes in the
      use of outpatient services or outcomes. Nevertheless, shorter hospital stays and
      the presence of more severely ill patients highlight the need for more attention
      to linkage to aftercare and enhancement of support networks in the community.

PMID- 15994712
TI  - Pathways to PTSD, part I: Children with burns.
AB  - OBJECTIVE: The goal of this study was to develop a model of risk factors for
      posttraumatic stress disorder (PTSD) in a group of acutely burned children.
      METHOD: Seventy-two children between the ages of 7 and 17 who were admitted to
      the hospital for an acute burn were eligible for study. Members of families who
      consented completed the Child PTSD Reaction Index, the Multidimensional Anxiety
      Scale for Children, and other self-report measures of psychopathology and
      environmental stress both during the hospitalization and 3 months following the
      burn. A path analytic strategy was used to build a model of risk factors for
      PTSD. RESULTS: Two pathways to PTSD were discerned: 1) from the size of the burn
      and level of pain following the burn to the child's level of acute separation
      anxiety, and then to PTSD, and 2) from the size of the burn to the child's level
      of acute dissociation following the burn, and then to PTSD. Together these
      pathways accounted for almost 60% of the variance in PTSD symptoms and
      constituted a model with excellent fit indices. CONCLUSIONS: These findings
      support a model of complex etiology for childhood PTSD in which two independent
      pathways may be mediated by different biobehavioral systems.

PMID- 15994713
TI  - Pathways to PTSD, part II: Sexually abused children.
AB  - OBJECTIVE: The goal of this research was to develop and test a prospective model
      of posttraumatic stress symptoms in sexually abused children that includes
      pretrauma, trauma, and disclosure-related pathways. METHOD: At time 1, several
      measures were used to assess pretrauma variables, trauma variables, and stress
      reactions upon disclosure for 156 sexually abused children ages 8 to 13 years. At
      the time 2 follow-up (7 to 36 months following the initial interview), the
      children were assessed for posttraumatic stress disorder (PTSD) symptoms.
      RESULTS: A path analysis involving a series of hierarchically nested ordinary
      least squares multiple regression analyses indicated three direct paths to PTSD
      symptoms: avoidant coping, anxiety/arousal, and dissociation, all measured during
      or immediately after disclosure of sexual abuse. Additionally, age and gender
      predicted avoidant coping, while life stress and age at abuse onset predicted
      symptoms of anxiety/arousal. Taken together, these pathways accounted for
      approximately 57% of the variance in PTSD symptoms. CONCLUSIONS: Symptoms
      measured at the time of disclosure constitute direct, independent pathways by
      which sexually abused children are likely to develop later PTSD symptoms. These
      findings speak to the importance of assessing children during the disclosure of
      abuse in order to identify those at greatest risk for later PTSD symptoms.

PMID- 15994714
TI  - Improving the rates of quitting smoking for veterans with posttraumatic stress
      disorder.
AB  - OBJECTIVE: Smoking is highly prevalent and refractory among people with
      posttraumatic stress disorder (PTSD). This study aimed to improve the rate of
      quitting smoking for veterans with PTSD by integrating treatment for nicotine
      dependence into mental health care. METHOD: Smokers undergoing treatment for PTSD
      (N=66) were randomly assigned to 1) tobacco use treatment delivered by mental
      health providers and integrated with psychiatric care (integrated care) versus 2)
      cessation treatment delivered separately from PTSD care by smoking-cessation
      specialists (usual standard of care). Seven-day point prevalence abstinence was
      the primary outcome, measured at 2, 4, 6, and 9 months after random assignment.
      Data were analyzed by using a generalized estimating equations approach following
      the intent-to-treat principle. RESULTS: Subjects assigned to integrated care were
      five times more likely than subjects undergoing the usual standard of care to
      abstain from smoking across follow-up assessment intervals (odds ratio=5.23).
      Subjects in the integrated care condition were significantly more likely than
      subjects in usual standard of care to receive transdermal nicotine and nicotine
      gum. They also received a greater number of smoking-cessation counseling
      sessions. Stopping smoking was not associated with worsening symptoms of PTSD or
      depression. CONCLUSIONS: Smoking-cessation interventions can be safely
      incorporated into routine mental health care for PTSD and are more effective than
      treatment delivered separately by a specialized smoking-cessation clinic.
      Integrating cessation treatment into psychiatric care may have the potential for
      improving smoking quit rates in other populations of chronically mentally ill
      smokers.

PMID- 15994715
TI  - Longitudinal course of posttraumatic stress disorder and posttraumatic stress
      disorder symptoms in a community sample of adolescents and young adults.
AB  - OBJECTIVE: Few studies have focused on the natural course of posttraumatic stress
      disorder (PTSD) and its determinants in samples of the general population. The
      authors examined determinants of remission and chronicity of PTSD and
      associations with other disorders in a prospective community sample. METHOD: The
      data were drawn from a prospective, longitudinal epidemiological study of
      adolescents and young adults (age 14-24 years) in Munich, Germany (N=2,548). The
      course of PTSD from baseline to follow-up 34-50 months later was studied in 125
      respondents with DSM-IV PTSD or subthreshold PTSD at baseline. RESULTS: Although
      52% of the PTSD cases remitted during the follow-up period, 48% showed no
      significant remission of PTSD symptoms. Respondents with a chronic course were
      more likely to experience new traumatic event(s) during follow-up (odds
      ratio=5.21, 95% confidence interval [CI]=1.95-13.92), to have higher rates of
      avoidant symptoms at baseline (odds ratio=10.16, 95% CI=1.73-59.51), and to
      report more help seeking (odds ratio=5.50, 95% CI=1.04-29.05), compared to
      respondents with remission. Rates of incident somatoform disorder (odds
      ratio=4.24, 95% CI=1.60-11.19) and other anxiety disorders (odds ratio=4.07, 95%
      CI=1.15-14.37) were also significantly associated with a chronic course.
      CONCLUSIONS: PTSD is often a persistent and chronic disorder. Specific symptom
      clusters--especially avoidant symptoms--might be associated with the course of
      PTSD. In addition, the occurrence of new traumatic events differentiates PTSD
      cases with a chronic course from those with remission.

PMID- 15994716
TI  - National trends in hospitalization of youth with intentional self-inflicted
      injuries.
AB  - OBJECTIVE: The authors examined national trends from 1990 to 2000 in the
      utilization of community hospital inpatient services by young people (5-20 years
      of age) with intentional self-inflicted injuries. METHOD: Discharge abstracts
      from a nationally representative sample of community hospitals were analyzed,
      with a focus on youth discharges (N=10,831) with a diagnosis of intentional self
      inflicted injury (ICD-9-CM: E950-E959). Census data were used to derive national
      population-based rates of self-inflicted injuries requiring inpatient treatment.
      Overall population-based trends in hospitalizations for self-inflicted injury
      were calculated and stratified by gender and age. Among youths hospitalized with
      a self-inflicted injury, trends were also calculated for length of stay,
      inpatient costs, method of injury, and associated mental disorder diagnoses.
      RESULTS: The annual hospitalization rate of youths with self-inflicted injuries
      declined from 49.1 per 100,000 in 1990 to 44.9 per 100,000 in 2000, and the mean
      length of inpatient stay significantly declined from 3.6 days to 2.7 days. Among
      the hospitalized patients, there were increases in the rate of cutting (4.3% to
      13.2%) and ingestion of acetaminophen (22.1% to 26.9%), antidepressants (10.0% to
      14.0%), and opiates (2.3% to 3.3%) as a cause of injury, whereas there were
      decreases in the ingestion of salicylates (14.9% to 10.2%) and barbiturates (1.5%
      to 0.7%). There were significant increases in the proportion of subjects with
      primary mental disorder discharge diagnoses of depressive disorder (29.2% to
      46.0%), bipolar disorder (1.3% to 8.2%), and substance use disorder (5.4% to
      10.7%) and significant decreases in the rate of adjustment disorders (22.2% to
      11.4%) and nonmental disorders (31.9% to 13.6%). After excluding cutting, which
      may be more closely related to self-mutilation than suicidal self-injury, the
      annual hospitalization rate of youths with self-inflicted injuries declined from
      47.2 per 100,000 in 1990 to 39.4 per 100,000 in 2000. CONCLUSIONS: Over the
      decade of study, young people admitted to community hospitals with self-inflicted
      injuries tended to have more severe psychiatric diagnoses and to be treated
      during shorter inpatient stays. These trends suggest that the role of youth
      inpatient care has narrowed, becoming focused on those with severe psychiatric
      disorders.

PMID- 15994717
TI  - Racial and ethnic differences in utilization of mental health services among high
      risk youths.
AB  - OBJECTIVE: Racial and ethnic disparities in mental health service use have been
      identified as a major public health problem. However, the extent to which these
      disparities may be accounted for by other confounding sociodemographic or
      clinical predictors of service use (e.g., family income, functional impairment,
      caregiver strain) is relatively unexplored, especially for youth services. The
      goal of this study was to test for racial/ethnic disparities in use of a variety
      of outpatient, inpatient, and informal mental health services among high-risk
      youths, with the effects of other predictive factors controlled. METHOD:
      Participants were 1,256 youths ages 6-18 years who received services in a large,
      publicly funded system of care (including the child welfare, juvenile justice,
      special education, alcohol and drug abuse, and mental health service sectors).
      Youths and caregivers were interviewed with established measures of mental health
      service use, psychiatric diagnoses, functional impairment, caregiver strain, and
      parental depression. RESULTS: Significant racial/ethnic group differences in
      likelihood of receiving any mental health service and, specifically, formal
      outpatient services were found after the effects of potentially confounding
      variables were controlled. Race/ethnicity did not exert a significant effect on
      the use of informal or 24-hour-care services. CONCLUSIONS: Racial/ethnic
      disparities in service use remain a public health problem.

PMID- 15994718
TI  - A 3-year panel study of mental disorders among adolescents in Taiwan.
AB  - OBJECTIVE: This study investigated the prevalence and changing trends of mental
      disorders and the effects of gender and urbanization among adolescents in Taiwan.
      METHOD: A random sample of seventh-grade students (N=1,070) was recruited from
      one urban and one rural junior high school in which 1,051 (98.2%) and 1,035
      (96.7%) were reassessed in the second and third years, respectively. A two-stage
      case identification was conducted by mental health professionals with the
      Schedule for Affective Disorders and Schizophrenia for School-Age Children
      Epidemiologic Version, supplemented by information from the Child Behavior
      Checklist. RESULTS: The weighted 3-month prevalence rates across the 3
      consecutive years for overall psychiatric disorders were 20.3%, 22.7%, and 14.8%,
      respectively. The most prevalent psychiatric condition was attention deficit
      hyperactivity disorder (ADHD) in the first 2 years and substance use disorders in
      the third. During the 3 years, the rates for ADHD, specific phobia, and social
      phobia decreased, and the rates for major depression and substance use disorders,
      conversely, increased. Although conduct disorder, ADHD, and substance use
      disorders were more prevalent among boys, the rates for major depression, social
      phobia, specific phobia, and adjustment disorder were higher among girls. Rural
      adolescents had higher rates of conduct disorder, oppositional defiant disorder,
      and substance use disorders than their urban counterparts. CONCLUSIONS: Our
      findings are similar to those of previous studies among adolescents in prevalence
      rates, changing trends of most mental disorders, and gender effects. The
      differential changing trends in various diagnostic groups may imply the
      importance of specific measures for prevention during adolescence.

PMID- 15994719
TI  - A randomized, double-blind, placebo-controlled trial of quetiapine in the
      treatment of bipolar I or II depression.
AB  - OBJECTIVE: There is a major unmet need for effective options in the treatment of
      bipolar depression. METHOD: Five hundred forty-two outpatients with bipolar I
      (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV)
      were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo.
      The primary efficacy measure was mean change from baseline to week 8 in the
      Montgomery-Asberg Depression Rating Scale total score. Additional efficacy
      assessments included the Hamilton Depression Rating Scale, Clinical Global
      Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh
      Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction
      Questionnaire. RESULTS: Quetiapine at either dose demonstrated statistically
      significant improvement in Montgomery-Asberg Depression Rating Scale total scores
      compared with placebo from week 1 onward. The proportions of patients meeting
      response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score
      improvement) at the final assessment in the groups taking 600 and 300 mg/day of
      quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The
      proportions of patients meeting remission criteria (Montgomery-Asberg Depression
      Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of
      quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day
      significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating
      Scale items, respectively, compared to placebo, including the core symptoms of
      depression. Treatment-emergent mania rates were low and similar for the
      quetiapine and placebo groups (3.2% and 3.9%, respectively). CONCLUSIONS:
      Quetiapine monotherapy is efficacious and well tolerated for the treatment of
      bipolar depression.

PMID- 15994720
TI  - Risperidone treatment of autistic disorder: longer-term benefits and blinded
      discontinuation after 6 months.
AB  - OBJECTIVE: Risperidone is effective for short-term treatment of aggression,
      temper outbursts, and self-injurious behavior in children with autism. Because
      these behaviors may be chronic, there is a need to establish the efficacy and
      safety of longer-term treatment with this agent. METHOD: The authors conducted a
      multisite, two-part study of risperidone in children ages 5 to 17 years with
      autism accompanied by severe tantrums, aggression, and/or self-injurious behavior
      who showed a positive response in an earlier 8-week trial. Part I consisted of 4
      month open-label treatment with risperidone, starting at the established optimal
      dose; part II was an 8-week randomized, double-blind, placebo-substitution study
      of risperidone withdrawal. Primary outcome measures were the Aberrant Behavior
      Checklist irritability subscale and the Clinical Global Impression improvement
      scale. RESULTS: Part I included 63 children. The mean risperidone dose was 1.96
      mg/day at entry and remained stable over 16 weeks of open treatment. The change
      on the Aberrant Behavior Checklist irritability subscale was small and clinically
      insignificant. Reasons for discontinuation of part I included loss of efficacy
      (N=5) and adverse effects (N=1). The subjects gained an average of 5.1 kg. Part
      II included 32 patients. The relapse rates were 62.5% for gradual placebo
      substitution and 12.5% for continued risperidone; this difference was
      statistically significant. CONCLUSIONS: Risperidone showed persistent efficacy
      and good tolerability for intermediate-length treatment of children with autism
      characterized by tantrums, aggression, and/or self-injurious behavior.
      Discontinuation after 6 months was associated with a rapid return of disruptive
      and aggressive behavior in most subjects.

PMID- 15994721
TI  - Generalizability of antidepressant efficacy trials: differences between depressed
      psychiatric outpatients who would or would not qualify for an efficacy trial.
AB  - OBJECTIVE: In recent years the generalizability of antidepressant efficacy trials
      has been questioned. Central to the question of generalizability is whether there
      are differences in clinical, demographic, and psychosocial characteristics
      between patients who would qualify for an antidepressant efficacy trial and those
      who would not qualify. METHOD: The authors compared three groups: 123 depressed
      patients who would qualify for an antidepressant efficacy trial, 289 whose
      symptom severity was too mild to qualify for an antidepressant efficacy trial,
      and 187 who would be excluded because they were suicidal or had a comorbid
      anxiety or substance use disorder. RESULTS: Compared with patients who would
      qualify for an antidepressant efficacy trial, patients who would be excluded
      because of comorbidity or suicidality were a more chronically ill group with more
      previous episodes, greater psychosocial impairment, and more personality
      pathology. CONCLUSIONS: These findings support further caution in generalizing
      the results from antidepressant efficacy trials to clinical populations.

PMID- 15994722
TI  - Strong inverse association between height and suicide in a large cohort of
      Swedish men: evidence of early life origins of suicidal behavior?
AB  - OBJECTIVE: Previous studies have found associations between poor fetal and infant
      growth and the risk of suicide. The authors' goal was to investigate the
      association between height--a measure of childhood growth--and suicide risk.
      METHOD: The authors conducted a record linkage study of the birth, conscription,
      mortality, family, and census register data of 1,299,177 Swedish men followed
      from age 18 to a maximum of age 49. RESULTS: There were 3,075 suicides over an
      average follow-up period of 15 years. There was a strong inverse association
      between height and suicide risk. In fully adjusted models, a 5-cm increase in
      height was associated with a 9% decrease in suicide risk. CONCLUSIONS: The strong
      inverse association between height and suicide may signify the importance of
      childhood exposure in the etiology of adult mental disorder or reflect
      stigmatization or discrimination encountered by short men in their adult lives.

PMID- 15994723
TI  - Is violent method of suicide a behavioral marker of lifetime aggression?
AB  - OBJECTIVE: The main purpose of this study was to investigate whether the method
      of suicide is a valid behavioral marker of a lifetime history of aggression.
      METHOD: The authors applied the psychological autopsy method to investigate 310
      individuals who committed suicide. They used structured clinical assessments and
      personality trait scales in interviews with family members of the deceased.
      RESULTS: Violent method was associated with a higher level of lifetime aggression
      and a higher level of impulsivity. In addition, violent method was associated
      with lifetime substance abuse or dependence and psychotic disorders. Controlling
      for age, sex, substance disorders, and other major psychopathology, the authors
      found that lifetime aggression and the interaction between impulsivity and
      aggressive behavior remained associated with violent method. CONCLUSIONS: These
      results support the use of violent method of suicide as a behavioral marker of a
      higher level of lifetime impulsive-aggressive behaviors.

PMID- 15994724
TI  - Prediction of panic response to a respiratory stimulant by reduced orbitofrontal
      cerebral blood flow in panic disorder.
AB  - OBJECTIVE: Lack of appropriate top-down governance by frontal cortical regions
      over a hypersensitive amygdala-centered fear neurocircuitry has been hypothesized
      to be central in the pathophysiology of panic disorder. The aim of this study was
      to examine regional cerebral blood flow changes in response to anxiety/panic
      provocation in subjects with panic disorder and healthy comparison subjects.
      METHOD: Quantitative water method positron emission tomography was used to obtain
      brain images of five untreated subjects with panic disorder and five healthy
      comparison subjects before and during anxiogenic challenge with intravenous
      doxapram, an acute respiratory stimulant. RESULTS: Baseline perfusion of the
      orbitofrontal cortex predicted panic attacks: lower perfusion was associated with
      heightened anxiety in response to doxapram challenge. CONCLUSIONS: The
      orbitofrontal cortex may be important in the regulation of responding to fear and
      is a potential area of aberrant functioning in panic disorder.

PMID- 15994725
TI  - Acute stress disorder and posttraumatic stress disorder in children and
      adolescents involved in assaults or motor vehicle accidents.
AB  - OBJECTIVE: The authors investigated acute stress disorder and later posttraumatic
      stress disorder (PTSD) in children and adolescents who had been involved in
      assaults or motor vehicle accidents. METHOD: They interviewed 93 patients 10-16
      years old who were seen in an emergency department for having been assaulted or
      involved in a motor vehicle accident within 4 weeks after the assault or accident
      to assess acute stress disorder. At 6 months, they reinterviewed 64 (68.8%) of
      the patients to assess PTSD. RESULTS: At initial interview, 18 (19.4%) of the 93
      patients had acute stress disorder and 23 (24.7%) met all acute stress disorder
      criteria except dissociation. At 6 months, eight of the 64 patients (12.5%) had
      PTSD. Acute stress disorder and PTSD did not differ in prevalence between
      patients who had been assaulted and those who had been in accidents. Sensitivity
      and specificity statistics and regression modeling revealed that the diagnosis of
      acute stress disorder was a good predictor of later PTSD but that dissociation
      did not play a significant role. CONCLUSIONS: Acute stress disorder has merit as
      a predictor of later PTSD in children and adolescents, but dissociation has
      questionable utility.

PMID- 15994726
TI  - Dysbetalipoproteinemia and clomipramine.

PMID- 15994727
TI  - 48,XXYY syndrome, mood disorder, and aggression.

PMID- 15994728
TI  - Antidepressant effect of ketamine during ECT.

PMID- 15994729
TI  - Clozapine-induced eosinophilic colitis.

PMID- 15994730
TI  - Sertraline- and mirtazapine-induced severe neutropenia.

PMID- 15994731
TI  - The significance of homocysteine levels in schizophrenia.

PMID- 15994732
TI  - Clinical trials during the prodromal stage of schizophrenia.

PMID- 15994733
TI  - Reduced spinophilin in schizophrenia.

PMID- 15994734
TI  - Physician suicide and drug abuse.

PMID- 15994735
TI  - Methodological concerns in a trial of ziprasidone and olanzapine.

PMID- 15994736
TI  - Methodological concerns in a trial of ziprasidone and olanzapine.

PMID- 15994737
TI  - Olanzapine and haloperidol for residual symptoms.

PMID- 15994738
TI  - Origin of the term "schizophrenia".

PMID- 15994739
TI  - History and perspectives of pituitary folliculo-stellate cell research.
AB  - Historically, the study of folliculo-stellate (FS) cells of the anterior
      pituitary dates back to the onset of electron microscopical observation of the
      pituitary gland. The morphological and electrophysiological characteristics,
      topographical distribution and contribution to intercellular junctions of these
      FS cells have been instrumental to the understanding of their putative function.
      Moreover, many studies have documented the role of FS cells as a source of newly
      discovered peptides, growth factors and cytokines. Quantitative
      immunohistochemical observation of FS cells in situ and functional in vitro
      studies, using either cultured FS cells or cells from an immortalized FS cell
      line, forwarded the notion of immunophenotypical and functional heterogeneity of
      the FS cell group. Double immunolabeling with a classical FS cell marker (S-100
      protein) and with major histocompatibility complex class II markers
      characteristic for dendritic cells (DC) have shown a considerable overlap of FS
      cells with DC. The latter cells are immunocompetent cells belonging to the
      mononuclear phagocyte system. In this review, the FS cell heterogeneity is
      discussed with respect to the question of their embryological origin and
      developmental fate and with respect to the physiological relevance of
      functionally heterogeneous subpopulations. Recent findings of a myeloid origin of
      part of the interstitial cells of the anterior pituitary are confronted by other
      developmental paradigms of pituitary cell differentiation. The possibility that
      FS cells represent an adult stem cell population of the pituitary is critically
      examined. Also the physiological role of FS cells in the interferon-gamma- and
      nitric oxide-mediated effects on pituitary hormone secretion is discussed. New
      approaches for the study of this enigmatic cell group using immortalized cell
      lines and new markers for an hitherto unrecognized pituitary cell population, the
      so-called 'side population', are evaluated.

PMID- 15994740
TI  - Glucocorticoids and outcome of radioactive iodine therapy for Graves'
      hyperthyroidism.

PMID- 15994741
TI  - Glucocorticoids do not influence the effect of radioiodine therapy in Graves'
      disease.
AB  - OBJECTIVE: We evaluated, in a retrospective study, whether glucocorticoids given
      in order to avoid initiation or aggravation of ophthalmopathy during radioiodine
      (131I) therapy have an inadvertent effect on the final thyroid function. METHODS:
      Consecutive patients with Graves' disease (median age 50 years, range 21-82
      years) treated with 131I therapy for the first time were included. Ninety-six
      patients (group 1) were given prednisolone (25 mg daily for 30 days beginning 2
      days before 131I therapy) because of present or previous mild ophthalmopathy or
      the presence of risk factors (tobacco smoking and high concentrations of TSH
      receptor antibodies) for developing this complication. One hundred and eleven
      patients received 131I therapy without prednisolone prophylaxis (group 2).
      RESULTS: The patients in group 1 were younger than those in group 2 (44.6+/-12.0
      years versus 51.3+/-15.1 years; P = 0.001). At 1 year post therapy the patients
      were classified as hypothyroid, euthyroid or hyperthyroid. In group 1, the
      numbers of patients were 23, 35 and 38, respectively, while the corresponding
      numbers in group 2 were 26, 40 and 45, respectively (P = 0.99 between groups).
      The cure rate (attainment of euthyroidism or hypothyroidism) was 60% in group 1
      and 59% in group 2 (P = 0.97). No significant between-group difference was found,
      neither in the median time-interval until development of hypothyroidism nor until
      recurrence of the hyperthyroid-ism. Using logistic regression the cure rate
      correlated negatively with age (P = 0.041) and the size of the thyroid gland (P =
      0.010) and positively with serum TSH at treatment (P = 0.034), whereas no
      significant impact was found for the use of prednisolone, gender, smoking,
      presence of anti-thyroid peroxidase antibodies, use of anti-thyroid drugs or the
      presence of eye symptoms. CONCLUSIONS: Although glucocorticoids in some contexts
      seem to attenuate the radiation-induced oxidative stress this had no impact on
      the final outcome following 131I therapy of patients with Graves' disease.

PMID- 15994742
TI  - Hip bone mineral density, bone turnover and risk of fracture in patients on long
      term suppressive L-thyroxine therapy for differentiated thyroid carcinoma.
AB  - OBJECTIVE: Untreated hyperthyroidism and treatment with high doses of thyroid
      hormone are associated with osteoporosis. However, their effect on bone turnover,
      their contribution to bone mineral density (BMD) in the context of other clinical
      risk factors for osteoporosis and the prevalence of vertebral fractures is not
      well documented. DESIGN: Cross-sectional study. METHODS: We studied 59 patients
      receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma
      (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral
      DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption
      was measured by C-telopeptides of type I collagen (ICTP) and bone formation by
      procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis
      were evaluated using a questionnaire. RESULTS: Z-scores of BMD were similar as
      the NHANES (National Health and Nutrition Examination Survey) III reference group
      in women and men, also after long-term (> 10 years) suppression therapy. Patients
      in the lowest and highest quartile of BMD showed significant differences in the
      presence of clinical risk factors. ICTP levels were significantly higher than in
      age-matched controls, PINP levels were not different. We found four patients with
      a prevalent vertebral fracture. CONCLUSIONS: We conclude that patients with well
      differentiated thyroid carcinoma are not at increased risk of developing low bone
      mass nor have a higher prevalence of vertebral fracture at least when treated
      with relatively low doses of L-thyroxine.

PMID- 15994743
TI  - Platelet-activating factor and human thyroid cancer.
AB  - OBJECTIVE: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic
      lipid mediator involved in several types of cancer in humans. The levels of PAF,
      lyso-PAF (the PAF precursor), phospholipase A2 activity (PLA2, the enzymatic
      activity implicated in lyso-PAF formation) and acetylhydrolase activity (AHA, the
      PAF-degrading enzyme) were investigated in various diseased thyroid tissues.
      SUBJECTS: Control and diseased tissue of patients with a hyperplastic goitre (n =
      14), a benign adenoma (n = 12) and a papillary thyroid carcinoma (n = 15) were
      investigated. RESULTS: PAF receptor transcripts were found in the human thyroid
      tissue. PAF, lyso-PAF, PLA2 and AHA were present in control thyroid tissues,
      their levels being significantly correlated with each other, suggesting tiny
      regulations of the PAF metabolic pathways inside the thyroid gland. PAF, lyso
      PAF, PLA2 and AHA levels remained unchanged in diseased tissues of patients with
      a hyperplastic goitre, a benign adenoma and a papillary thyroid carcinoma. No
      difference was found between PAF, lyso-PAF, PLA2 and AHA levels with respect to
      the TNM tumour status and the histological sub-type of papillary thyroid
      carcinoma. No correlation was found between tissue PAF levels and those of
      vascular endothelial growth factor and basic fibroblast growth factor, two
      angiogenic growth factors involved in thyroid cancer and that mediate their
      effect through PAF release in breast and colorectal cancer. CONCLUSION: PAF, PAF
      receptor transcripts and the enzymatic activities implicated in PAF production
      and degradation are present in the thyroid gland. While the physiological role of
      PAF is presently unknown in thyroid physiology, this study highlights no evidence
      for a potentially important role of PAF during human thyroid cancer, a result
      that markedly differs from breast and colorectal ones.

PMID- 15994744
TI  - In vivo and in vitro effects of statins on lymphocytes in patients with
      Hashimoto's thyroiditis.
AB  - BACKGROUND: Statins have apoptotic effects on many cell types. Hashimoto's
      thyroiditis (HT) is an autoimmune disease in which cell-mediated autoimmune
      mechanisms are pathogenetically involved. OBJECTIVE: The aim of this study was to
      evaluate the in vivo effects of Simvastatin on thyroid function, lymphocyte
      subtypes and also to investigate the apoptotic effects of Simvastatin,
      Mevastatin, Pravastatin and Cerivastatin on lymphocytes from patients with HT.
      METHODS: In the first part of the study, 11 patients with HT and subclinical
      hypothyroidism (SH) were given Simvastatin (20 mg/day) for 8 weeks. Ten patients
      with SH and HT served as the control group. No treatment was given to controls.
      Thyroid function, C-reactive protein (CRP) levels and lymphocyte subtypes of both
      groups were determined before the study and after 8 weeks. In the second part of
      the study, the apoptotic effects of statins on lymphocytes were evaluated in
      patients with HT (n = 10) and normal subjects (n = 10) in vitro. Apoptosis was
      investigated by using Annexin-V and propidium iodide. Lymphocytes from patients
      and controls were incubated with different concentrations of Simvastatin,
      Cerivastatin, Mevastatin and Pravastatin. RESULTS: An increase in serum free tri
      iodothyronine and free thyroxine levels and a decrease in TSH levels were
      observed (P < 0.05) with Simvastatin treatment. CD4+ cells and B lymphocytes
      increased whilst CD8+ cells, natural killer cells and activated T lymphocytes
      decreased significantly in the treatment group (P < 0.05). The CRP level of the
      group also decreased with Simvastatin but it did not reach significance (P =
      0.057). None of parameters was found to be different from the baseline in the
      control group. In in vitro experiments, apoptosis was observed in CD3 + (both in
      CD8+ and CD4+ cells) with all statins in both patient and control samples.
      Mevalonate, which was used in experiments, reversed apoptosis in some but not all
      samples. CONCLUSIONS: The results of this study suggested that Simvastatin is an
      immune modulatory agent and improves thyroid function in patients with HT. This
      effect is probably mediated via lymphocyte apoptosis as demonstrated with in
      vitro experiments and is not confined to Simvastatin since Mevastatin,
      Pravastatin and Cerivastatin also induced apoptosis in lymphocytes.

PMID- 15994745
TI  - Development and clinical impact of thyroglobulin antibodies in patients with
      differentiated thyroid carcinoma during the first 3 years after thyroidectomy.
AB  - OBJECTIVE AND DESIGN: Cross-sectional studies have reported an increased
      prevalence of circulating thyroglobulin autoantibodies (TgAbs) in patients with
      differentiated thyroid carcinoma (DTC). With the advent of more sensitive assays,
      a longitudinal study monitoring the development of TgAb levels after ablative
      therapy was warranted. METHODS: One hundred and twelve consecutive patients with
      follicular cell-derived thyroid cancer were followed for 3 years. All patients
      had been thyroidectomized and received, on average, two radioiodine therapies.
      Residual tissue was quantified scintigraphically by 131I 24-h uptake. TgAb and
      thyroglobulin (Tg) serum levels were determined with a sensitive direct
      radioligand assay and an IRMA respectively. RESULTS: The prevalence of TgAbs at
      the initial examination was 29% (median 130 U/ml). During follow-up, TgAb levels
      rose transiently in one-tenth of the patients, but the prevalence of demonstrable
      TgAbs decreased to < 10% after 3 years. The median serum half-life of TgAbs in
      treated DTC patients was 10 weeks. At initial examination (when all patients
      still had residual thyroid tissue and 17 had metastases), rising TgAb levels were
      correlated with the inability to detect Tg in 4, 30 and 73% of the patients, when
      initial TgAbs were < 6, 6-50 or > 50 U/ml respectively. While the Tg recovery
      test was valid for all patients, an in vitro dilution assay with TgAb serum
      reduced Tg values by up to 32%. CONCLUSIONS: The development and course of TgAbs
      in DTC patients cannot be predicted by initial or residual tumour volume, TgAb or
      Tg levels. The presence of TgAbs, even in low concentrations, may cause Tg
      underestimation despite valid recovery tests in DTC patients.

PMID- 15994746
TI  - An individualized GH dose regimen for long-term GH treatment in Japanese patients
      with adult GH deficiency.
AB  - OBJECTIVES: To investigate the effects of growth hormone (GH) treatment, using a
      dose-adjustment regimen based on serum insulin-like growth factor (IGF)-I
      concentrations, in adult Japanese hypopituitary patients with GH deficiency.
      STUDY DESIGN: Japanese patients who had initially been administered GH (n = 31)
      or placebo (n = 28) in a 24-week double-blind study received individualized GH
      treatment in an open-label study for 48 weeks. Body composition from dual-energy
      X-ray absorptiometry (DXA) and serum IGF-I, IGF-binding protein 3 (IGFBP-3) and
      lipid levels were determined centrally. RESULTS: Significant increases in lean
      body mass (4.5%) and decreases in fat mass (-10.5%) were observed in the group
      that received individualized GH doses in the present open-label study following
      placebo in the double-blind study. This was comparable with the changes observed
      in these parameters (4.7 and -9.2%, respectively) with fixed-dose GH treatment in
      the double-blind study; this latter group maintained these improvements
      throughout the open-label study. Individualized dose adjustment allowed for more
      moderate dose increases than the fixed-dose titration method. Individualized
      dosing also resulted in a lower mean dose for adult-onset compared with childhood
      onset GH-deficient patients (0.032+/-0.019 versus 0.061+/-0.023 mg/kg per week
      for patients treated with GH for 48 weeks in the open-label study following
      placebo in the double-blind study). Dosing patterns in the two groups were
      paralleled by the changes in IGF-I and IGFBP-3. The incidence of oedema and cases
      with high IGF-I level were less frequent under the IGF-I controlled regimen
      compared with those during the fixed-dose titration method. CONCLUSION:
      Individualized GH administration based on IGF-I levels was safe and effective.
      This regimen demonstrated differences in dose requirements between adult- and
      childhood-onset patients. An individualized dose regimen is recommended in adult
      Japanese GH-deficient patients.

PMID- 15994747
TI  - Limited predictive value of an acute test with subcutaneous octreotide for long
      term IGF-I normalization with Sandostatin LAR in acromegaly.
AB  - OBJECTIVES: To study whether the growth hormone (GH) response after the
      subcutaneous administration 50 microg of octreotide (acute octreotide test) has
      any predictive value for long-term IGF-I normalization with Sandostatin LAR.
      DESIGN: Twenty four therapy-naive patients with active acromegaly were studied.
      RESULTS: > 75% GH decrease in the acute octreotide test predicted long-term IGF-I
      normalization with Sandostatin LAR in 8/11 (73%) of patients. 3/13 (23%) patients
      with < 75% GH decrease in the acute octreotide test were long-term biochemically
      controlled with Sandostatin LAR. Using the > 75% GH reduction criterion, the
      sensitivity and specificity of this test for predicting long-term normalization
      of serum IGF-I with Sandostatin LAR treatment were 73% and 77%, respectively
      (positive and negative predictive values: 73% and 77%, respectively). 6/8 (75%)
      patients with GH suppression to levels < 1.1 microg/l and 9/16 (56%) patients
      with GH suppression to levels < 2 microg/l in the acute octreotide test showed
      normalization of serum IGF-I with long-term Sandostatin LAR treatment. The
      sensitivity and specificity of GH suppression < 1.1 microg/l for predicting of
      the long-term normalization of serum IGF-I with Sandostatin LAR therapy were 55%
      and 85%, respectively (positive and negative predictive values: 75% and 69%,
      respectively). The sensitivity and specificity of GH suppression < 2 microg/l for
      predicting of the long-term normalization of serum IGF-I with Sandostatin LAR
      therapy were 82% and 46%, respectively (positive and negative predictive values:
      56% and 75%, respectively). CONCLUSION: The acute octreotide is not recommended
      for clinical decision making with regard to long-term treatment using the long
      acting somatostatin analog Sandostatin LAR in acromegaly.

PMID- 15994748
TI  - Circulating ghrelin in thyroid dysfunction is related to insulin resistance and
      not to hunger, food intake or anthropometric changes.
AB  - OBJECTIVE: Ghrelin is a gastric peptide that plays a role in appetite
      stimulation, energy balance and possibly in insulin resistance. Hyperthyroidism
      is a situation where negative energy balance and insulin resistance coexist,
      while in hypothyroidism a positive energy balance and normal insulin sensitivity
      predominate. We investigated ghrelin levels and their relationship with hunger,
      food intake and both anthropometric and insulin resistance parameters in patients
      with thyroid dysfunction. DESIGN AND METHODS: We studied 24 hyperthyroid and 17
      hypothyroid patients before and after normalisation of thyroid hormone levels and
      their respective body mass index (BMI)-matched control group. We measured plasma
      ghrelin levels, homeostasis model assessment of insulin resistance (HOMA-IR)
      index, a hunger score, mean three-day calorie intake and anthropometric
      parameters. RESULTS: In hyperthyroidism, HOMA-IR index was higher (3.21 +/- 0.60
      vs 1.67 +/- 0.15 mMmU/l; P = 0.014, t test for independent data) and ghrelin
      levels were lower (463.6 +/- 36.4 vs 561.1 +/- 32.1 pg/ml; P = 0.041, Mann
      Whitney U-test) than in its control group and both normalised after treatment
      (HOMA-IR: 2.28 +/- 0.38 mMmU/l; P = 0.106, t test for independent data, and
      ghrelin: 539.7 +/- 45.4 pg/ml; P = 0.549, Mann-Whitney U-test). Glucose, as a
      component of HOMA-IR index was the only predictor for ghrelin levels (beta = 
      0.415, P = 0.044, stepwise multiple regression analysis). In hypothyroidism, HOMA
      IR index and ghrelin levels were similar to those in its control group both
      before and after treatment. In both thyroid dysfunction states, no correlations
      were observed between changes in ghrelin levels and in free T4, free T3,
      anthropometric parameters, total calorie intake and hunger score. CONCLUSIONS: In
      thyroid dysfunction states, ghrelin levels seemed to be in relation to insulin
      resistance and not to energy balance and food intake regulation, as seen in other
      physiological and pathological states.

PMID- 15994749
TI  - Body composition in young adult survivors of childhood acute lymphoblastic
      leukaemia.
AB  - OBJECTIVE: Obesity is frequently reported in patients treated for childhood
      leukaemia. Obesity, particularly abdominal obesity, is one of the main
      characteristics of the metabolic syndrome and a risk factor for cardiovascular
      disease and non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: All patients
      treated for acute lymphoblastic leukaemia (ALL) before the onset of puberty in
      the region of western Sweden, between 1973 and 1985, and in first remission, were
      included. 35 out of 47 patients aged 20-32 years participated. 19 patients had
      received cranial radiotherapy, and the median follow-up time was 20 years. The
      focus of this report was to study body composition and signs of the metabolic
      syndrome and correlate the findings to spontaneous growth hormone (GH) secretion.
      METHODS: Body composition was assessed using dual-energy X-ray absorbtiometry
      (DEXA). We analyzed serum concentrations of insulin, glucose, leptin and lipids.
      RESULTS: No patient was obese according to World Health Organization criteria
      (body mass index, BMI > or = 30 kg/m2) but one-third were overweight (BMI 25-29.9
      kg/m2). The maximal GH peak during 24 h (GHmax) was correlated to percentage of
      total body fat (r = -0.42; P = 0.017), trunk fat (r = -0.5; P = 0.005) and fat
      free mass (r = 0.42; P = 0.017). GHmax was also correlated to s-triglycerides (r
      = -0.54; P = 0.001), low-density lipoprotein-cholesterol (r = -0.382; P = 0.024)
      and high-density lipoprotein-cholesterol (r = 0.45; P = 0.007). CONCLUSIONS: We
      found little effect on BMI but an increased percentage of total body fat,
      especially trunk fat, and a tendency for an unfavourable lipid profile in adult
      survivors of childhood leukaemia. These findings were related to low endogenous
      GH secretion due to cranial irradiation.

PMID- 15994750
TI  - Influence of gender, age and renal function on plasma adiponectin level: the
      Tanno and Sobetsu study.
AB  - DESIGN: The aim of this study was to determine the association between aging and
      adiponectin level from the aspect of the influence of renal function and sex
      hormones in humans. METHODS: Serum adiponectin and blood urea nitrogen (BUN)
      levels were measured in 964 subjects (372 males) aged 60.3+/-12.5 years.
      Testosterone and free testosterone levels were measured in 123 males, and estrone
      and estradiol levels were measured in 114 females. The subjects were divided into
      two age groups; 65 years of age or older (Age > or = 65 group) and less than 65
      years of age (Age < 65 group). RESULTS: Adiponectin level increased linearly with
      aging in males, whereas it increased dramatically in females until their 50s. The
      patterns of changes in adiponectin were similar to those in BUN. In multiple-
      regression analysis using adiponectin as a dependent variable BUN was selected as
      a significant independent variable in all subjects and in subjects in the Age >
      or = 65 group, whereas bioactive sex hormones were not selected. CONCLUSIONS: A
      decrease in adiponectin clearance in the kidney may be the cause of high levels
      of adiponectin in the elderly. Adiponectin level seems to be influenced more
      strongly by BUN than by sex hormones and to be increased by a decline in renal
      function with aging.

PMID- 15994751
TI  - Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype
      association in Middle European patients with congenital adrenal hyperplasia.
AB  - OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21)
      and the genotype- phenotype correlation in patients with congenital adrenal
      hyperplasia (CAH) registered in the Middle European Society for Pediatric
      Endocrinology CAH database, and to design a reliable and rational approach for
      CYP21 mutation detection in Middle European populations. DESIGN AND METHODS:
      Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298
      family members. Low-resolution genotyping was performed to detect the eight most
      common point mutations. High-resolution genotyping, including Southern blotting
      and sequencing was performed to detect CYP21 gene deletions, conversions, point
      mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and
      Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study
      group. A good genotype-phenotype correlation was observed, with the exception of
      Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping
      could not identify the causative mutation or distinguish homozygosity from
      hemizygosity. Using high-resolution genotyping, the causative mutations could be
      identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was
      found in one simple virilising CAH (SV-CAH) patient from Austria. In the
      remaining seven patients polymorphisms were identified as the leading sequence
      alteration. The presence of elevated basal and ACTH-stimulated 17
      hydroxyprogesterone, premature pubarche, advanced bone age and clitoral
      hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of
      nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most
      common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in
      exon 3, it should be possible to identify the mutation in 94-99% of the diseased
      alleles in any investigated Middle European population. In patients with a mild
      form of the disease and no detectable mutation CYP21 gene polymorphisms should be
      considered as a plausible disease-causing mutation.

PMID- 15994752
TI  - High dose estrogen treatment increases bone mineral density in male-to-female
      transsexuals receiving gonadotropin-releasing hormone agonist in the absence of
      testosterone.
AB  - OBJECTIVE: To study the effect of estrogen (E) on the male skeleton in the
      absence of testosterone (T). DESIGN: Retrospective analyses of 40 middle-aged
      transsexuals treated with subcutaneous injections of gonadotropin-releasing
      hormone agonist every 4 weeks and oral 17-beta-estradiol-valerat 6 mg/day over
      two years until reassignment surgery. METHODS: The bone mineral density (BMD) in
      the femoral neck and lumbar spine (L2-L4) was measured with dual-energy X-ray
      absorptiometry at the beginning of cross-sex hormone treatment, after 12 and 24
      months, and serum T, E, sex hormone-binding globulin (SHBG), calcitonin (CAL),
      osteocalcin (OSC), and urinary free deoxypyridinoline (DPD) were measured.
      RESULTS: After 12 months, a significant increase in BMD in the lumbar spine from
      1.2 to 1.234 g/cm2 and after 24 months to 1.274 g/cm2 was observed. There was a
      significant increase in BMD in the femoral neck area from 1.068 to 1.109 g/cm(2)
      after 24 months. There was a significant decrease in serum T levels from 18.65 to
      0.57 nmol/l after 12 months, and to 0.62 nmol/l after 24 months, a significant
      increase in SHBG levels from 50.09 to 125 nmol/l after 12 months, and to 130
      nmol/l after 24 months, and a significant increase in serum E levels from 73.42
      to 881.6 pmol/l after 12 months, and to 923.62 pmol/l after 24 months of cross
      sex hormone treatment. Serum levels of CAL, OSC and urinary DPD were unchanged.
      CONCLUSION: We conclude that high dose E treatment is able to increase BMD
      significantly in the femoral neck and lumbar spine independently of serum T
      levels in middle-aged men. There is no risk of osteoporosis developing in male-to
      female transsexuals receiving GnRHa when there is an adequate E substitution.

PMID- 15994753
TI  - Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial
      function in non-obese young women with polycystic ovary syndrome.
AB  - OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit elevated levels of
      serum C-reactive protein (CRP) and impaired endothelium dysfunction which are
      directly correlated with insulin resistance. Because rosiglitazone improves
      insulin sensitivity, we tested whether rosiglitazone treatment ameliorates high
      sensitivity (hs)CRP levels and endothelial dysfunction in these patients. DESIGN:
      Thirty-one women with PCOS were recruited (mean age, 24.7+/-3.9 (s.e.) years;
      mean body mass index (BMI), 25.6+/-3.2 kg/m2). All women were treated with 4 mg
      rosiglitazone daily for 12 months. METHODS: Serum levels of testosterone, LH,
      FSH, sex hormone-binding globulin (SHBG), insulin and hsCRP were measured. The
      BMI, hirsutism scores and insulin sensitivity indices were calculated before and
      after treatment. Arterial endothelium and smooth muscle function was measured by
      examining brachial artery responses to endothelium-dependent and endothelium
      independent stimuli before and after treatment. RESULTS: After treatment with
      rosigitazone there were significant decreases in serum testosterone (91.2+/-37.5
      vs 56.1+/-21.8 ng/dl; P < 0.01) and fasting insulin concentrations (12.5+/-7.6 vs
      8.75+/-4.03 microU/ml; P = 0.015). Insulin resistance indices were significantly
      improved after rosiglitazone treatment (P < 0.05). There were no significant
      changes in BMI, waist circumference, serum total cholesterol, low-density
      lipoprotein (LDL)-cholesterol, FSH and LH levels. Hirsutism score was decreased
      significantly after treatment (10.8+/-1.8 vs 7.6+/-1.7; P < 0.05). Twenty-four of
      the women reverted to regular menstrual cycles. Levels of SHBG increased
      significantly after treatment (28.7+/-8.7 vs 48.4+/-11.2 nmol/l; P < 0.01). Serum
      hsCRP levels were decreased significantly after rosiglitazone treatment (0.25+/
      0.1 vs 0.09+/-0.02 mg/dl; P = 0.006). There was also significant improvement in
      endothelium-dependent vascular responses after rosiglitazone treatment (9.9+/-3.9
      vs 16.4+/-5.1%; P < 0.01). CONCLUSIONS: We conclude that rosiglitazone treatment
      improves insulin sensitivity in women with PCOS. It also decreases androgen
      production without significant weight gain. More importantly, it has beneficial
      effects on endothelial dysfunction and low-grade chronic inflammation in normal
      weight young women with PCOS.

PMID- 15994754
TI  - p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP
      in FRTL-5 thyroid cells.
AB  - OBJECTIVE: Thyrotropin activates the cAMP pathway in thyroid cells, and
      stimulates cell cycle progression in cooperation with insulin or insulin-like
      growth factor-I. Because p38 mitogen-activated protein kinases (p38 MAPKs) were
      stimulated by cAMP in the FRTL-5 rat thyroid cell line, we investigated (i) the
      effect of the specific inhibition of p38 MAPKs on FRTL-5 cell proliferation and
      (ii) the mechanism of action of p38 MAPKs on cell cycle control, by studying the
      expression and/or the activity of several cell cycle regulatory proteins in FRTL
      5 cells. METHODS: DNA synthesis was monitored by incorporation of [(3)H]thymidine
      into DNA and the cell cycle distribution was assessed by fluorescence-activated
      cell sorter analysis. Expression of cell cycle regulatory proteins was determined
      by Western blot analysis. Cyclin-dependent kinase 2 (Cdk2) activity associated to
      cyclin E was immunoprecipitated and was measured by an in vitro kinase assay.
      RESULTS: SB203580, an inhibitor of alpha and beta isoforms of p38 MAPKs, but not
      its inactive analog SB202474, inhibited DNA synthesis and the G1-S transition
      induced by forskolin plus insulin. SB203580 inhibited specifically p38 MAPK
      activity but not other kinase activities such as Akt and p70-S6 kinase. Treatment
      of FRTL-5 cells with SB203580 decreased total and cyclin E-associated Cdk2 kinase
      activity stimulated with forskolin and insulin. However, inhibition of p38 MAPKs
      by SB203580 was without effect on total cyclin E and Cdk2 levels. The decrease in
      Cdk2 kinase activity caused by SB203580 treatment was not due to an increased
      expression of p21(Cip1) or p27(Kip1) inhibitory proteins. In addition, SB203580
      affected neither Cdc25A phosphatase expression nor Cdk2 Tyr-15 phosphorylation.
      Inhibition of p38 MAPKs decreased Cdk2-cyclin E activation by regulating the
      subcellular localization of Cdk2 and its phosphorylation on Thr-160. CONCLUSIONS:
      These results indicate that p38 MAPK activity is involved in the regulation of
      cell cycle progression in FRTL-5 thyroid cells, at least in part by increasing
      nuclear Cdk2 activity.

PMID- 15994755
TI  - Efficacy of chimeric molecules directed towards multiple somatostatin and
      dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting
      pituitary adenomas classified as partially responsive to somatostatin analog
      therapy.
AB  - OBJECTIVE: This study compared the potency of a somatostatin receptor (sstr)2
      sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule,
      BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing,
      enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM
      23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are
      partially responsive to octreotide or lanreotide. MATERIALS AND METHODS: The
      sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs
      was tested in cell cultures at various concentrations. RESULTS: In all tumors,
      the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels+/-s.e.m.
      0.4+/-0.1, 5.3+/-1.9 and 2.0+/-0.4 copy/copy beta-glucuronidase). In 13 tumors,
      the maximal suppression of GH secretion produced by BIM-23A387 (30+/-3%) and BIM
      23244 (28+/-3%) was greater than that produced by octreotide (23+/-3%). In six
      out of 13 tumors, BIM-23A758, BIM-23A760 and BIM- 23A761 produced greater maximal
      suppression of GH secretion than octreotide (33+/-5, 38+/-2 and 41+/-2 vs 24+/
      2%). Their EC(50) values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective
      than BIM-23A387 in GH suppression (41+/-2 vs 32+/-4%). The new chimeric molecules
      produced maximal PRL suppression greater than octreotide (62+/-8 to 74+/-5 vs
      46+/-11%). CONCLUSIONS: Novel dopamine-somatostatin chimeric molecules with
      differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced
      significatly greater suppression of GH and PRL than either octreotide or single
      receptor-interacting ligands in tumors from patients classified as only partially
      responsive to octreotide therapy. The higher efficacy of the chimeric compounds
      was, at least partially, linked to their high affinity for sstr2 (IC50 1-10
      pmol/l). The other mechanisms by which such molecules produce an enhanced
      inhibition of GH remain to be elucidated.

PMID- 15994756
TI  - Differential gene expression in pituitary adenomas by oligonucleotide array
      analysis.
AB  - OBJECTIVES: Microarray technology allows for the expression profile of many
      thousands of genes to be quantified at the same time, and has resulted in novel
      discoveries about the tumour biology of a number of cancers. We sought to do this
      in pituitary adenomas, the most common intracranial neoplasm. METHODS: Affymetrix
      GeneChip HG-U133A oligonucleotide arrays covering 14 500 well-characterised genes
      from the human genome were used to study pooled RNA for each of the four major
      pituitary adenoma subtypes. Individual gene-expression levels in the tumours were
      compared relative to the expression profile in normal pooled pituitary RNA. Three
      differentially expressed genes with potential importance in tumourigenesis were
      chosen for validation by real-time quantitative PCR on the original tumours and
      on an additional 26 adenomas. RESULTS: Bioinformatic analysis showed that 3906
      genes and 351 expressed sequence tags were differentially expressed among all
      pituitary tumour subtypes. Lysosomal-associated protein transmembrane- 4-beta
      (LAPTM4B), a novel gene upregulated in hepatocellular carcinoma, was
      significantly over-expressed in adrenocorticotrophin (ACTH)-secreting adenomas
      and non-functioning pituitary adenomas (NFPAs). Bcl-2-associated athanogene
      (BAG1), an anti-apoptotic protein found at high levels in a number of human
      cancers, was significantly over-expressed in growth hormone-secreting and
      prolactin-secreting adenomas and NFPAs. The cyclin-dependent kinase inhibitor
      p18, in which murine gene deletion has been shown to produce pituitary ACTH cell
      hyperplasia and adenomas, was significantly under-expressed in ACTH-secreting
      adenomas. CONCLUSIONS: Expression array analysis of pituitary adenomas using the
      Affymetrix GeneChip HG-U133A arrays appears to be a valid method of identifying
      genes that may be important in tumour pathogenesis.

PMID- 15994757
TI  - Relationship between serum concentrations of leptin, soluble leptin receptor,
      testosterone and IGF-I, and growth during the first year of postnatal life in the
      male rhesus monkey, Macaca mulatta.
AB  - OBJECTIVES: Subnormal leptin levels in low birth weight infants may allow for
      catch-up growth during infancy. Scant data are available that relate growth with
      circulating leptin during normal infancy in primates. The current study objective
      was to examine the association between serum leptin, its soluble receptor (sOB
      R), testosterone and IGF-I concentrations, and body weight during infancy in male
      rhesus monkeys. DESIGN: Hormone levels were assessed longitudinally in animals (n
      = 7) from birth until 1 year of age. RESULTS: Body weight increased during the
      first 6 months of life and was strongly correlated with rising IGF-I levels and,
      as IGF-I plateaued and then declined during the second half of the year, body
      weight gain decelerated. In contrast, leptin levels declined gradually with age
      during the first year of life in conjunction with increasing body weight. There
      was no association between body weight gain and serum leptin levels or between
      serum testosterone and leptin values. Since sOB-R levels also declined with
      leptin values, it does not appear that levels of bioavailable leptin changed
      during infancy. CONCLUSIONS: The data do not support the contention that leptin
      regulates growth during infancy, but the close association between IGF-I levels
      and body weight suggested that this hormone may regulate growth in infant male
      monkeys. The failure to observe an association between serum testosterone and
      leptin concentrations suggested that leptin is not involved in the activation of
      the hypothalamic-pituitary -testicular axis during this developmental period.

PMID- 15994758
TI  - Endoplasmic reticulum stress induces Wfs1 gene expression in pancreatic beta
      cells via transcriptional activation.
AB  - OBJECTIVE: The WFS1 gene encodes an endoplasmic reticulum (ER) membrane-embedded
      protein. Homozygous WFS1 gene mutations cause Wolfram syndrome, characterized by
      insulin-deficient diabetes mellitus and optic atropy. Pancreatic beta-cells are
      selectively lost from the patient's islets. ER localization suggests that WFS1
      protein has physiological functions in membrane trafficking, secretion,
      processing and/or regulation of ER calcium homeostasis. Disturbances or
      overloading of these functions induces ER stress responses, including apoptosis.
      We speculated that WFS1 protein might be involved in these ER stress responses.
      DESIGN AND METHODS: Islet expression of the Wfs1 protein was analyzed
      immunohistochemically. Induction of Wfs1 upon ER stress was examined by Northern
      and Western blot analyses using three different models: human skin fibroblasts,
      mouse pancreatic beta-cell-derived MIN6 cells, and Akita mouse-derived Ins2
      (96Y/Y) insulinoma cells. The human WFS1 gene promoter-luciferase reporter
      analysis was also conducted. RESULT: Islet beta-cells were the major site of Wfs1
      expression. This expression was also found in delta-cells, but not in alpha
      cells. WFS1 expression was transcriptionally up-regulated by ER stress-inducing
      chemical insults. Treatment of fibroblasts and MIN6 cells with thapsigargin or
      tunicamycin increased WFS1 mRNA. WFS1 protein also increased in response to
      thapsigargin treatment in these cells. WFS1 gene expression was also increased in
      Ins2 (96Y/Y) insulinoma cells. In these cells, ER stress was intrinsically
      induced by mutant insulin expression. The WFS1 gene promoter-luciferase reporter
      system revealed that the human WFS1 promoter was activated by chemically induced
      ER stress in MIN6 cells, and that the promoter was more active in Ins2 (96Y/Y)
      cells than Ins2 (wild/wild) cells. CONCLUSION: Wfs1 expression, which is
      localized to beta- and delta-cells in pancreatic islets, increases in response to
      ER stress, suggesting a functional link between Wfs1 and ER stress.

PMID- 15994759
TI  - Experimentally-induced hyperthyroidism is associated with activation of the rat
      hypothalamic-pituitary-adrenal axis.
AB  - OBJECTIVE: Previous studies on the effects of altered thyroid function on the
      secretion and metabolism of adrenocortical hormones suggest a degree of
      adrenocortical hyperactivity in hyperthyroidism. We have previously shown that
      experimentally-induced hyperthyroidism is associated with significant alterations
      in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing
      hormone (oCRH) that are contingent upon the duration of the altered thyroid
      function. The purpose of this study was to assess the time-dependent effects of
      hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal
      (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal
      cortex. METHODS: The functional integrity of the HPA axis was examined in vivo in
      sham-thyroidectomized male Sprague-Dawley rats given placebo or in
      thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days.
      Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to
      assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in
      response to low-dose adrenocorticotropic hormone (ACTH), following suppression of
      the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to
      basal plasma ACTH, corticosterone and thyroid indices were also determined.
      RESULTS: Basal plasma corticosterone and corticosterone binding globulin (CBG)
      concentrations were significantly increased in short- and long-term hyperthyroid
      rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were
      significantly increased. Basal plasma ACTH levels were similar to controls.
      Although plasma ACTH responses to hypoglycemic stress and IL-1alpha
      administration in both short- and long-term hyperthyroidism were normal,
      corticosterone responses to the ACTH release during the administration of these
      stimuli were significantly increased. The adrenal reserve was significantly
      elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was
      associated with a significant reduction in adrenocortical reserve. A significant
      increase in adrenal weights and a decrease in thymus weights were observed in
      both short- and long-term hyperthyroidism. CONCLUSIONS: The available data
      confirms that hyperthyroidism is associated with hypercorticosteronemia, although
      the locus that is principally affected still remains unclear. Despite the
      sustained hyperactivity of the HPA axis, long-term experimentally-induced
      hyperthyroidism is associated with diminished adrenal functional reserve. The
      alterations in HPA function in states of disturbed thyroid function were found to
      be somewhat more pronounced as the duration of thyroid dysfunction increased.

PMID- 15994761
TI  - Sulfolobus tengchongensis spindle-shaped virus STSV1: virus-host interactions and
      genomic features.
AB  - A virus infecting the hyperthermophilic archaeon Sulfolobus tengchongensis has
      been isolated from a field sample from Tengchong, China, and characterized. The
      virus, denoted STSV1 (Sulfolobus tengchongensis spindle-shaped virus 1), has the
      morphology of a spindle (230 by 107 nm) with a tail of variable length (68 nm on
      average) at one end and is the largest of the known spindle-shaped viruses. After
      infecting its host, the virus multiplied rapidly to high titers (>10(10) PFU/ml).
      Replication of the virus retarded host growth but did not cause lysis of the host
      cells. STSV1 did not integrate into the host chromosome and existed in a carrier
      state. The STSV1 DNA was modified in an unusual fashion, presumably by virally
      encoded modification systems. STSV1 harbors a double-stranded DNA genome of
      75,294 bp, which shares no significant sequence similarity to those of
      fuselloviruses. The viral genome contains a total of 74 open reading frames
      (ORFs), among which 14 have a putative function. Five ORFs encode viral
      structural proteins, including a putative coat protein of high abundance. The
      products of the other nine ORFs are probably involved in polysaccharide
      biosynthesis, nucleotide metabolism, and DNA modification. The viral genome
      divides into two nearly equal halves of opposite gene orientation. This
      observation as well as a GC-skew analysis point to the presence of a putative
      viral origin of replication in the 1.4-kb intergenic region between ORF1 and
      ORF74. Both morphological and genomic features identify STSV1 as a novel virus
      infecting the genus Sulfolobus.

PMID- 15994762
TI  - Stimulation of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase
      activity by the NS3 protease domain and by HCV RNA-dependent RNA polymerase.
AB  - Hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses multiple enzyme
      activities. The N-terminal one-third of NS3 primarily functions as a serine
      protease, while the remaining two-thirds of NS3 serve as a helicase and
      nucleoside triphosphatase. Whether the multiple enzyme activities of NS3 are
      functionally interdependent and/or modulated by other viral NS proteins remains
      unclear. We performed biochemical studies to examine the functional
      interdependence of the NS3 protease and helicase domains and the modulation of
      NS3 helicase by NS5B, an RNA-dependent RNA polymerase (RdRp). We found that the
      NS3 protease domain of the full-length NS3 (NS3FL) enhances the NS3 helicase
      activity. Additionally, HCV RdRp stimulates the NS3FL helicase activity by more
      than sevenfold. However, the helicase activity of the NS3 helicase domain was
      unaffected by HCV RdRp. Glutathione S-transferase pull-down as well as
      fluorescence anisotropy results revealed that the NS3 protease domain is required
      for specific NS3 and NS5B interaction. These findings suggest that HCV RdRp
      regulates the functions of NS3 during HCV replication. In contrast, NS3FL does
      not increase NS5B RdRp activity in vitro, which is contrary to a previously
      published report that the HCV NS3 enhances NS5B RdRp activity.

PMID- 15994763
TI  - Castanospermine, a potent inhibitor of dengue virus infection in vitro and in
      vivo.
AB  - Previous studies have suggested that alpha-glucosidase inhibitors such as
      castanospermine and deoxynojirimycin inhibit dengue virus type 1 infection by
      disrupting the folding of the structural proteins prM and E, a step crucial to
      viral secretion. We extend these studies by evaluating the inhibitory activity of
      castanospermine against a panel of clinically important flaviviruses including
      all four serotypes of dengue virus, yellow fever virus, and West Nile virus.
      Using in vitro assays we demonstrated that infections by all serotypes of dengue
      virus were inhibited by castanospermine. In contrast, yellow fever virus and West
      Nile virus were partially and almost completely resistant to the effects of the
      drug, respectively. Castanospermine inhibited dengue virus infection at the level
      of secretion and infectivity of viral particles. Importantly, castanospermine
      prevented mortality in a mouse model of dengue virus infection, with doses of 10,
      50, and 250 mg/kg of body weight per day being highly effective at promoting
      survival (P < or = 0.0001). Correspondingly, castanospermine had no adverse or
      protective effect on West Nile virus mortality in an analogous mouse model.
      Overall, our data suggest that castanospermine has a strong antiviral effect on
      dengue virus infection and warrants further development as a possible treatment
      in humans.

PMID- 15994764
TI  - Human cytomegalovirus TRS1 and IRS1 gene products block the double-stranded-RNA
      activated host protein shutoff response induced by herpes simplex virus type 1
      infection.
AB  - Human cytomegalovirus (HCMV) attachment and entry stimulates the expression of
      cellular interferon-inducible genes, many of which target important cellular
      functions necessary for viral replication. Double-stranded RNA-dependent host
      protein kinase (PKR) is an interferon-inducible gene product that limits viral
      replication by inhibiting protein translation in the infected cell. It was
      anticipated that HCMV encodes gene products that facilitate the evasion of this
      PKR-mediated antiviral response. Using a deltagamma1 34.5 herpes simplex virus
      type 1 (HSV-1) recombinant that triggers PKR-mediated protein synthesis shutoff,
      experiments identified an HCMV gene product expressed in the initial hours of
      infection that allows continued protein synthesis in the infected cell.
      Recombinant HSV-1 viruses expressing either the HCMV TRS1 or IRS1 protein
      demonstrate that either of these HCMV gene products allows the deltagamma1 34.5
      recombinant viruses to evade PKR-mediated protein shutoff and maintain late viral
      protein synthesis.

PMID- 15994765
TI  - Mycobacterial codon optimization enhances antigen expression and virus-specific
      immune responses in recombinant Mycobacterium bovis bacille Calmette-Guerin
      expressing human immunodeficiency virus type 1 Gag.
AB  - Although its potential for vaccine development is already known, the introduction
      of recombinant human immunodeficiency virus (HIV) genes to Mycobacterium bovis
      bacille Calmette-Guerin (BCG) has thus far elicited only limited responses. In
      order to improve the expression levels, we optimized the codon usage of the HIV
      type 1 (HIV-1) p24 antigen gene of gag (p24 gag) and established a codon
      optimized recombinant BCG (rBCG)-p24 Gag which expressed a 40-fold-higher level
      of p24 Gag than did that of nonoptimized rBCG-p24 Gag. Inoculation of mice with
      the codon-optimized rBCG-p24 Gag elicited effective immunity, as evidenced by
      virus-specific lymphocyte proliferation, gamma interferon ELISPOT cell induction,
      and antibody production. In contrast, inoculation of animals with the
      nonoptimized rBCG-p24 Gag induced only low levels of immune responses.
      Furthermore, a dose as small as 0.01 mg of the codon-optimized rBCG per animal
      proved capable of eliciting immune responses, suggesting that even low doses of a
      codon-optimized rBCG-based vaccine could effectively elicit HIV-1-specific immune
      responses.

PMID- 15994766
TI  - Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of
      innate antiretroviral defense factors.
AB  - Foamy viruses are a family of complex retroviruses that establish common,
      productive infections in a wide range of nonhuman primates. In contrast, humans
      appear nonpermissive for foamy virus replication, although zoonotic infections do
      occur. Here we have analyzed the ability of primate and mouse APOBEC3G proteins
      to inhibit the infectivity of primate foamy virus (PFV) virions produced in their
      presence. We demonstrate that several APOBEC3 proteins can potently inhibit the
      infectivity of a PFV-based viral vector. This inhibition correlated with the
      packaging of inhibitory APOBEC3 proteins into PFV virions, due to a specific PFV
      Gag/APOBEC3 interaction, and resulted in the G to A hypermutation of PFV reverse
      transcripts. While inhibition of PFV virion infectivity by primate APOBEC3
      proteins was largely relieved by coexpression of the PFV Bet protein, a
      cytoplasmic auxiliary protein of previously uncertain function, Bet failed to
      relieve inhibition caused by murine APOBEC3. PFV Bet bound to human, but not
      mouse, APOBEC3 proteins in coexpressing cells, and this binding correlated with
      the specific inhibition of their incorporation into PFV virions. Of note, both
      PFV Bet and a second Bet protein, derived from an African green monkey foamy
      virus, rescued the infectivity of Vif-deficient human immunodeficiency virus type
      1 (HIV-1) virions produced in the presence of African green monkey APOBEC3G and
      blocked the incorporation of this host factor into HIV-1 virion particles.
      However, neither foamy virus Bet protein reduced APOBEC3 protein expression
      levels in virion producer cells. While these data identify the foamy virus Bet
      protein as a functional ortholog of the HIV-1 Vif auxiliary protein, they also
      indicate that Vif and Bet block APOBEC3 protein function by distinct mechanisms.

PMID- 15994767
TI  - Detailed mapping of the nuclear export signal in the Rous sarcoma virus Gag
      protein.
AB  - The Rous sarcoma virus (RSV) Gag polyprotein undergoes transient nuclear
      trafficking as an intrinsic part of the virus assembly pathway. Nuclear export of
      Gag is crucial for the efficient production of viral particles and is
      accomplished through the action of a leptomycin B (LMB)-dependent nuclear export
      signal (NES) in the p10 domain (L. Z. Scheifele, R. A. Garbitt, J. D. Rhoads, and
      L. J. Parent, Proc. Natl. Acad. Sci. USA 99:3944-3949, 2002). We have now mapped
      the nuclear export activity to the C-terminal portion of the p10 sequence and
      identified the four hydrophobic amino acids within this region that comprise a
      leucine-rich NES. Alteration of these hydrophobic residues resulted in the
      accumulation of Gag proteins within the nucleus and a budding defect greater than
      that obtained with LMB treatment of cells expressing the wild-type Gag protein
      (Scheifele et al., Proc. Natl. Acad. Sci. USA 99:3944-3949, 2002). In addition,
      export of Gag from the nucleus was found to be a rate-limiting step in virus-like
      particle production. Consistent with a role for the NES sequence in viral
      replication, this cluster of hydrophobic residues in p10 is conserved across a
      wide range of avian retroviruses. Furthermore, naturally occurring substitutions
      within this region in related viruses maintained nuclear export activity and
      remained sensitive to the activity of LMB. Using gain-of-function approaches, we
      found that the hydrophobic motif in p10 was sufficient to promote the nuclear
      export of a heterologous protein and was positionally independent within the Gag
      polyprotein. Finally, the export pathway was further defined by the ability of
      specific nucleoporin inhibitors to prevent the egress of Gag from the nucleus,
      thereby identifying additional cellular mediators of RSV replication.

PMID- 15994768
TI  - Activation of the N-Ras-PI3K-Akt-mTOR pathway by hepatitis C virus: control of
      cell survival and viral replication.
AB  - The hepatitis C virus (HCV) replication complex is localized within detergent
      resistant membranes or lipid rafts. We analyzed the protein contents of detergent
      resistant fractions isolated from Huh7 cells expressing a self-replicating full
      length HCV-1b genome. Using two-dimensional gel electrophoresis followed by mass
      spectrometry, we identified N-Ras as one of the proteins in which expression was
      increased in the detergent-resistant fractions from HCV genomic replicon clones
      compared to control cells. N-Ras is an activator of the phosphatidylinositol-3
      kinase (PI3K)-Akt pathway. We found that the activities of PI3K and Akt, as well
      as the activity of their downstream target, mTOR, in the HCV-replicating cells
      were increased. Both PI3K-Akt- and mTOR-dependent pathways have been shown to
      promote cell survival. In agreement with this, HCV replicon cells were resistant
      to serum starvation-induced apoptosis. We also characterized the role of this
      pathway in HCV replication. Reduction of N-Ras expression by transfection of N
      Ras small interfering RNA (siRNA) resulted in increased replication of HCV. We
      observed a similar increase in HCV replication in cells treated with the PI3K
      inhibitor LY294002 and in cells transfected with mTOR siRNA. Taken together,
      these data suggest that increased N-Ras levels in subcellular sites of HCV
      replication and stimulation of the prosurvival PI3K-Akt pathway and mTOR by HCV
      not only protect cells against apoptosis but also contribute to the maintenance
      of steady-state levels of HCV replication. These effects may contribute to the
      establishment of persistent infection by HCV.

PMID- 15994769
TI  - Two subclasses of Kaposi's sarcoma-associated herpesvirus lytic cycle promoters
      distinguished by open reading frame 50 mutant proteins that are deficient in
      binding to DNA.
AB  - A transcriptional activator encoded in open reading frame 50 (ORF50) of the
      Kaposi's sarcoma-associated herpesvirus (KSHV) genome initiates the viral lytic
      cycle. Here we classify four lytic cycle genes on the basis of several
      characteristics of the ORF50 response elements (ORF50 REs) in their promoters:
      nucleotide sequence homology, the capacity to bind ORF50 protein in vitro, the
      ability to bind the cellular protein RBP-Jkappa in vitro, and the capacity to
      confer activation by DNA binding-deficient mutants of ORF50 protein. ORF50
      expressed in human cells binds the promoters of PAN and K12 but does not bind
      ORF57 or vMIP-1 promoters. Conversely, the RBP-Jkappa protein binds ORF57 and
      vMIP-1 but not PAN or K12 promoters. DNA binding-deficient mutants of ORF50
      protein differentiate these two subclasses of promoters in reporter assays; the
      PAN and K12 promoters cannot be activated, while the ORF57 and vMIP-1 promoters
      are responsive. Although DNA binding-deficient mutants of ORF50 protein are
      defective in activating direct targets, they are nonetheless capable of
      activating the lytic cascade of KSHV. Significantly, DNA binding-deficient ORF50
      mutants are competent to autostimulate expression of endogenous ORF50 and to
      autoactivate ORF50 promoter reporters. The experiments show that ORF50 protein
      activates downstream targets by at least two distinct mechanisms: one involves
      direct binding of ORF50 REs in promoter DNA; the other mechanism employs
      interactions with the RBP-Jkappa cellular protein bound to promoter DNA in the
      region of the ORF50 RE. The DNA binding-deficient mutants allow classification of
      ORF50-responsive genes and will facilitate study of the several distinct
      mechanisms of activation of KSHV lytic cycle genes that are under the control of
      ORF50 protein.

PMID- 15994770
TI  - RING-H2 protein WSSV249 from white spot syndrome virus sequesters a shrimp
      ubiquitin-conjugating enzyme, PvUbc, for viral pathogenesis.
AB  - Modification of proteins by ubiquitin is essential for numerous cellular
      processes. The RING-H2 finger motif has been implicated in ubiquitin-conjugating
      enzyme (E2)-dependent ubiquitination. Four proteins, WSSV199, WSSV222, WSSV249,
      and WSSV403, from white spot syndrome virus (WSSV) contain the RING-H2 motif.
      Here we report that WSSV249 physically interacts with a shrimp ubiquitin
      conjugating enzyme, PvUbc, and mediates ubiquitination through its RING-H2 motif
      in the presence of E1 and PvUbc. Mutations of the putative zinc coordination
      residues in the RING-H2 domain of WSSV249, however, ablate ubiquitination
      efficiency. In addition, the RING-H2 domain of WSSV249 is capable of
      ubiquitination with UbcH1, UbcH2, UbcH5a, UbcH5b, UbcH5c, UbcH6, and UbcH10,
      respectively, exhibiting a low degree of E2 specificity. Significantly, the
      expression of WSSV249 and PvUbc increased during infection, as revealed by real
      time PCR. Furthermore, in situ hybridization showed that WSSV249 and PvUbc
      display similar expression patterns in infected shrimps, and immunofluorescence
      and immunohistochemistry assays showed an increase of PvUbc in infected shrimp
      cells. These results suggest that the RING-H2 protein WSSV249 from WSSV may
      function as an E3 ligase via sequestration of PvUbc for viral pathogenesis in
      shrimp.

PMID- 15994771
TI  - Involvement of nuclear export in human papillomavirus type 18 E6-mediated
      ubiquitination and degradation of p53.
AB  - The E6 protein from high-risk human papillomaviruses (HPVs) targets the p53 tumor
      suppressor for degradation by the proteasome pathway. This ability contributes to
      the oncogenic potential of these viruses. However, several aspects concerning the
      mechanism of E6-mediated p53 degradation at the cellular level remain to be
      clarified. This study therefore examined the role of cell localization and
      ubiquitination in the E6-mediated degradation of p53. As demonstrated within,
      following coexpression both p53 and high-risk HPV type 18 (HPV-18) E6 (18E6)
      shuttle from the nucleus to the cytoplasm. Mutation of the C-terminal nuclear
      export signal (NES) of p53 or treatment with leptomycin B inhibited the 18E6
      mediated nuclear export of p53. Impairment of nuclear export resulted in only a
      partial reduction in 18E6-mediated degradation, suggesting that both nuclear and
      cytoplasmic proteasomes can target p53 for degradation. This was also consistent
      with the observation that 18E6 mediated the accumulation of polyubiquitinated p53
      in the nucleus. In comparison, a p53 isoform that localizes predominantly to the
      cytoplasm was not targeted for degradation by 18E6 in vivo but could be degraded
      in vitro, arguing that nuclear p53 is the target for E6-mediated degradation.
      This study supports a model in which (i) E6 mediates the accumulation of
      polyubiquitinated p53 in the nucleus, (ii) E6 is coexported with p53 from the
      nucleus to the cytoplasm via a CRM1 nuclear export mechanism involving the C
      terminal NES of p53, and (iii) E6-mediated p53 degradation can be mediated by
      both nuclear and cytoplasmic proteasomes.

PMID- 15994772
TI  - A somatic knockout of CBF1 in a human B-cell line reveals that induction of CD21
      and CCR7 by EBNA-2 is strictly CBF1 dependent and that downregulation of
      immunoglobulin M is partially CBF1 independent.
AB  - CBF1 is a cellular highly conserved DNA binding factor that is ubiquitously
      expressed in all tissues and acts as a repressor of cellular genes. In Epstein
      Barr virus growth-transformed B-cell lines, CBF1 serves as a central DNA adaptor
      molecule for several viral proteins, including the viral transactivator Epstein
      Barr virus nuclear antigen 2 (EBNA-2). EBNA-2 binds to CBF1 and thereby gains
      access to regulatory regions of target genes and activates transcription. We have
      inactivated the CBF1 gene by homologous recombination in the human B-cell line
      DG75 and characterized changes in cellular gene expression patterns upon loss of
      CBF1 and activation of EBNA-2. CBF1-negative DG75 cells were viable and
      proliferated at wild-type rates. Loss of CBF1 was not sufficient to release
      repression of the previously described EBNA-2 target genes CD21 or CCR7, whereas
      induction of both target genes by EBNA-2 required CBF1. In contrast, repression
      of immunoglobulin M by EBNA-2 was mainly CBF1 independent. CBF1-negative DG75 B
      cells thus provide an excellent tool to dissect CBF1-dependent and -independent
      functions exerted by the EBNA-2 protein in future studies.

PMID- 15994773
TI  - Equine infectious anemia virus Gag p9 function in early steps of virus infection
      and provirus production.
AB  - We have previously reported that serial truncation of the Gag p9 protein of
      equine infectious anemia virus (EIAV) revealed a progressive loss in replication
      phenotypes in transfected cells, such that a proviral mutant (E32) expressing the
      N-terminal 31 amino acids of p9 produced infectious virus particles similarly to
      parental provirus, while a proviral mutant (K30) with two fewer amino acids
      produced replication-defective virus particles, despite containing apparently
      normal levels of processed Gag and Pol proteins (C. Chen, F. Li, and R. C.
      Montelaro, J. Virol. 75:9762-9760, 2001). Based on these observations, we sought
      in the current study to identify the precise defect in K30 virion infection of
      permissive equine dermal (ED) cells. The results of these experiments clearly
      demonstrated that K30 virions entered target ED cells and produced early (minus
      strand strong-stop) and late (Gag) viral DNA products as efficiently as did the
      replication-competent E32 mutant and parental EIAV(UK) viruses. However, in
      contrast to the replication-competent E32 mutant and parental viruses, infection
      with K30 mutant virus failed to produce detectable two-long-terminal-repeat DNA
      circles, stable integrated provirus, virus-specific Gag mRNA expression, or
      intracellular viral protein expression. Taken together, these data demonstrate
      that the K30 mutant is defective in the ability to produce sufficient nuclear
      viral DNA to establish a productive infection in ED cells. Thus, these
      observations indicate for the first time that the EIAV Gag p9 protein performs a
      critical role in viral DNA production and processing to provirus during EIAV
      infection, in addition to its previously defined role in viral budding mediated
      by the p9 L domain.

PMID- 15994774
TI  - Influenza virus infection increases p53 activity: role of p53 in cell death and
      viral replication.
AB  - The induction of apoptotic cell death is a hallmark of influenza virus infection.
      Although a variety of cellular and viral proteins have been implicated in this
      process, to date no conserved cellular pathway has been identified. In this
      study, we report that the tumor suppressor protein p53 is essential for the
      induction of cell death in influenza virus-infected cells. In primary human lung
      cells, influenza virus increased p53 protein levels. This was also noted in the
      human lung cell line A549, along with the up-regulation of p53-dependent gene
      transcription. Reduction of p53 activity in A549 cells inhibited influenza virus
      induced cell death as measured by trypan blue exclusion and caspase activity.
      These findings were not cell type specific. Influenza virus-induced cell death
      was absent in mouse embryo fibroblasts isolated from p53 knockout mice, which was
      not the case in wild-type mouse embryo fibroblasts, suggesting that p53 is a
      common cellular pathway leading to influenza virus-induced cell death.
      Surprisingly, inhibiting p53 activity led to elevated virus replication.
      Mechanistically, this may be due to the decrease in interferon signaling in p53
      deficient cells, suggesting that functional p53 is involved in the interferon
      response to influenza infection. To our knowledge, these are the first studies
      demonstrating that p53 is involved in influenza virus-induced cell death and that
      inhibiting p53 leads to increased viral titers, potentially through modulation of
      the interferon response.

PMID- 15994775
TI  - Evaluating the immunogenicity of a disulfide-stabilized, cleaved, trimeric form
      of the envelope glycoprotein complex of human immunodeficiency virus type 1.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)
      complex comprises three gp120 exterior glycoproteins each noncovalently linked to
      a gp41 transmembrane glycoprotein. Monomeric gp120 proteins can elicit antibodies
      capable of neutralizing atypically sensitive test viruses in vitro, but these
      antibodies are ineffective against representative primary isolates and the gp120
      vaccines failed to provide protection against HIV-1 transmission in vivo.
      Alternative approaches to raising neutralizing antibodies are therefore being
      pursued. Here we report on the antibody responses generated in rabbits against a
      soluble, cleaved, trimeric form of HIV-1(JR-FL) Env. In this construct, the gp120
      and gp41 moieties are covalently linked by an intermolecular disulfide bond (SOS
      gp140), and an I559P substitution has been added to stabilize gp41-gp41
      interactions (SOSIP gp140). We investigated the value of DNA priming and compared
      the use of membrane-bound and soluble priming antigens and of repeat boosting
      with soluble and particulate protein antigen. Compared to monomeric gp120, SOSIP
      gp140 trimers elicited approximately threefold lower titers of anti-gp120
      antibodies. Priming with DNA encoding a membrane-bound form of the SOS gp140
      protein, followed by several immunizations with soluble SOSIP gp140 trimers,
      resulted in antibodies capable of neutralizing sensitive strains at high titers.
      A subset of these sera also neutralized, at lower titers, HIV-1(JR-FL) and some
      other primary isolates in pseudovirus and/or whole-virus assays. Neutralization
      of these viruses was immunoglobulin mediated and was predominantly caused by
      antibodies to gp120 epitopes, but not the V3 region.

PMID- 15994776
TI  - A human T-cell leukemia virus type 1 regulatory element enhances the
      immunogenicity of human immunodeficiency virus type 1 DNA vaccines in mice and
      nonhuman primates.
AB  - Plasmid DNA vaccines elicit potent and protective immune responses in numerous
      small-animal models of infectious diseases. However, their immunogenicity in
      primates appears less potent. Here we investigate a novel approach that optimizes
      regulatory elements in the plasmid backbone to improve the immunogenicity of DNA
      vaccines. Among various regions analyzed, we found that the addition of a
      regulatory sequence from the R region of the long terminal repeat from human T
      cell leukemia virus type 1 (HTLV-1) to the cytomegalovirus (CMV)
      enhancer/promoter increased transgene expression 5- to 10-fold and improved
      cellular immune responses to human immunodeficiency virus type 1 (HIV-1)
      antigens. In cynomolgus monkeys, DNA vaccines containing the CMV
      enhancer/promoter with the HTLV-1 R region (CMV/R) induced markedly higher
      cellular immune responses to HIV-1 Env from clades A, B, and C and to HIV-1 Gag
      Pol-Nef compared with the parental DNA vaccines. These data demonstrate that
      optimization of specific regulatory elements can substantially improve the
      immunogenicity of DNA vaccines encoding multiple antigens in small animals and in
      nonhuman primates. This strategy could therefore be explored as a potential
      method to enhance DNA vaccine immunogenicity in humans.

PMID- 15994777
TI  - Efficient axonal localization of alphaherpesvirus structural proteins in cultured
      sympathetic neurons requires viral glycoprotein E.
AB  - Pseudorabies virus (PRV) glycoprotein E (gE) is a type I viral membrane protein
      that facilitates the anterograde spread of viral infection from the peripheral
      nervous system to the brain. In animal models, a gE-null mutant infection spreads
      inefficiently from presynaptic neurons to postsynaptic neurons (anterograde
      spread of infection). However, the retrograde spread of infection from post- to
      presynaptic neurons remains unaffected. Here we show that gE is required for wild
      type localization of viral structural proteins in axons of infected neurons.
      During a gE-null PRV infection, a subset of viral glycoproteins, capsids, and
      tegument proteins enter and localize to the axon inefficiently. This defect is
      most obvious in the distal axon and growth cones. However, axonal entry and
      localization of other viral membrane proteins and endogenous cellular proteins
      remains unaffected. Neurons infected with gE-null mutants produce wild-type
      levels of viral structural proteins and infectious virions in the cell body. Our
      results indicate that reduced axonal targeting of viral structural proteins is a
      compelling explanation for the lack of anterograde spread in neural circuits
      following infection by a gE-null mutant.

PMID- 15994778
TI  - Herpes simplex virus type 1 capsids transit by the trans-Golgi network, where
      viral glycoproteins accumulate independently of capsid egress.
AB  - Egress of herpes capsids from the nucleus to the plasma membrane is a complex
      multistep transport event that is poorly understood. The current model proposes
      an initial envelopment at the inner nuclear membrane of capsids newly assembled
      in the nucleus. The capsids are then released in cytosol by fusion with the outer
      nuclear membrane. They are finally reenveloped at a downstream organelle before
      traveling to the plasma membrane for their extracellular release. Although the
      trans-Golgi network (TGN) is often cited as a potential site of reenvelopment,
      other organelles have also been proposed, including the Golgi, endoplasmic
      reticulum-Golgi intermediate compartment, aggresomes, tegusomes, and early or
      late endosomes. To clarify this important issue, we followed herpes simplex virus
      type 1 egress by immunofluorescence under conditions that slowed intracellular
      transport and promoted the accumulation of the otherwise transient reenvelopment
      intermediate. The data show that the capsids transit by the TGN and point to this
      compartment as the main reenvelopment site, although a contribution by endosomes
      cannot formally be excluded. Given that viral glycoproteins are expected to
      accumulate where capsids acquire their envelope, we examined this prediction and
      found that all tested could indeed be detected at the TGN. Moreover, this
      accumulation occurred independently of capsid egress. Surprisingly, capsids were
      often found immediately adjacent to the viral glycoproteins at the TGN.

PMID- 15994779
TI  - Differential susceptibility to human immunodeficiency virus type 1 infection of
      myeloid and plasmacytoid dendritic cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs)
      plays an important role in HIV-1 transmission and pathogenesis. Here, we studied
      the susceptibility of ex vivo-isolated CD11c+ myeloid DCs (MDCs) and CD123+
      plasmacytoid DCs (PDCs) to HIV-1 infection and the function of these cells early
      after infection. Both DC subsets were susceptible to CCR5- and CXCR4-using HIV-1
      isolates (BaL and IIIB, respectively). However, MDCs were more susceptible to HIV
      1(BaL) infection than donor-matched PDCs. In addition, HIV-1(BaL) infected MDCs
      more efficiently than HIV-1(IIIB), whereas PDCs were equally susceptible to both
      isolates. While exposure to HIV-1 alone resulted in only weak maturation of DCs,
      Toll-like receptor 7/8 ligation induced full maturation in both infected and
      uninfected DCs. Maturation did not increase HIV-1 replication in infected DCs,
      and infected DCs retained their ability to produce tumor necrosis factor alpha
      after stimulation. Both HIV-1 isolates induced alpha interferon production
      exclusively in PDCs, irrespective of productive infection. In conclusion, PDCs
      and MDCs were susceptible to HIV-1 infection, but neither displayed functional
      defects as a consequence of infection. The difference in susceptibility of PDCs
      and MDCs to HIV-1 may have implications for HIV-1 transmission and DC-mediated
      transfer of HIV-1 to T cells.

PMID- 15994780
TI  - A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African
      green monkey TRIM5alpha determines species-specific restriction of simian
      immunodeficiency virus SIVmac infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) efficiently enters cells of Old World
      monkeys but encounters a block before reverse transcription. This restriction is
      mediated by a dominant repressive factor. Recently, a member of the tripartite
      motif (TRIM) family proteins, TRIM5alpha, was identified as a blocking factor in
      a rhesus macaque cDNA library. Among Old World monkey cell lines, the African
      green monkey kidney cell line CV1 is highly resistant to not only HIV-1 but also
      simian immunodeficiency virus SIVmac infection. We analyzed TRIM5alpha of CV1
      cells and HSC-F cells, a T-cell line from a cynomolgus monkey, and found that
      both CV1- and HSC-F-TRIM5alphas could inhibit CD4-dependent HIV-1 infection, as
      well as vesicular stomatitis virus glycoprotein-mediated infection. CV1
      TRIM5alpha could also inhibit SIVmac infection, whereas HSC-F-TRIM5alpha could
      not. In the SPRY (B30.2) domain of CV1-TRIM5alpha, there was a 20-amino-acid
      duplication that was not present in HSC-F-TRIM5alpha. A chimeric TRIM5alpha
      containing 37 amino acid residues from CV1-TRIM5alpha, which spanned the 20-amino
      acid duplication, in the background of HSC-F-TRIM5alpha fully gained the ability
      to inhibit SIVmac infection. Conversely, the mutant CV1-TRIM5alpha lacking the 20
      amino-acid duplication completely lost the ability to restrict SIVmac infection.
      These findings clearly indicated that a specific region of 37 amino acid residues
      in the SPRY domain of CV1-TRIM5alpha contained a determinant of species-specific
      restriction of SIVmac.

PMID- 15994781
TI  - Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is
      attenuated in cynomolgus macaques and associated with early T-lymphocyte
      responses.
AB  - Because most studies of AIDS pathogenesis in nonhuman primates have been
      performed in Indian-origin rhesus macaques (Macaca mulatta), little is known
      about lentiviral pathogenicity and control of virus replication following
      infection of alternative macaque species. Here, we report the consequences of
      simian-human immunodeficiency virus SHIV-89.6P and SIVmac251 infection in
      cynomolgus (Macaca fascicularis) and rhesus macaques of Chinese origin. Compared
      to the pathogenicity of the same viruses in Indian rhesus macaques, both
      cynomolgus and Chinese rhesus macaques showed lower levels of plasma virus. By 9
      to 10 months after infection, both viruses became undetectable in plasma more
      frequently in cynomolgus than in either Chinese or Indian rhesus macaques.
      Furthermore, after SHIV-89.6P infection, CD4+ T-cell numbers declined less and
      survival was longer in cynomolgus and Chinese rhesus macaques than in Indian
      rhesus macaques. This attenuated pathogenicity was associated with gamma
      interferon ELISPOT responses to Gag and Env that were generated earlier and of
      higher frequency in cynomolgus than in Indian rhesus macaques. Cynomolgus
      macaques also developed higher titer neutralizing antibodies against SHIV-89.6 at
      10 and 20 weeks postinoculation than Indian rhesus macaques. These studies
      demonstrate that the pathogenicity of nonhuman primate lentiviruses varies
      markedly based on the species or geographic origin of the macaques infected and
      suggest that the cellular immune responses may contribute to the control of
      pathogenicity in cynomolgus macaques. While cynomolgus and Chinese rhesus
      macaques provide alternative animal models of lentiviral infection, the lower
      levels of viremia in cynomolgus macaques limit the usefulness of infection of
      this species for vaccine trials that utilize viral load as an experimental
      endpoint.

PMID- 15994782
TI  - Parvovirus nonstructural proteins induce an epigenetic modification through
      histone acetylation in host genes and revert tumor malignancy to benignancy.
AB  - Several malignant tumor cells become apoptotic and revert to the benign phenotype
      upon parvovirus infection. Recently, we demonstrated that the rat parvovirus
      RPV/UT also induces apoptosis in the rat thymic lymphoma cell line C58(NT)D.
      However, a minority of cells that escaped apoptosis showed properties different
      from the parental cells, such as resistance to apoptosis, enhanced cell
      adherence, and suppressed tumorigenicity. The present study was performed to
      determine the molecular mechanism of parvovirus-induced phenotypic modification,
      including oncosuppression. We demonstrated that the nonstructural (NS) proteins
      of RPV/UT induced apoptosis in C58(NT)D cells and suppressed tumor growth in
      vivo. Interestingly, NS proteins induced the expression of ciliary neurotrophic
      factor receptor alpha, which is up-regulated in revertant cell clones, and
      enhanced histone acetylation of its gene. These results indicate that parvoviral
      NS regulate host gene expression through histone acetylation, suggesting a
      possible mechanism of oncosuppression.

PMID- 15994783
TI  - Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton
      rats.
AB  - Human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae
      family causing acute respiratory tract infections, especially in young children.
      We studied the pathogenesis of this viral infection in two experimental small
      animal models (BALB/c mice and cotton rats). Significant viral replication in the
      lungs of both animals was found following an intranasal challenge of 10(8) 50%
      tissue culture infectious doses (TCID50) and persisted for <2 and <3 weeks in the
      case of cotton rats and mice, respectively. Peak viral loads were found on day 5
      postinfection in both mice (mean of 1.92 x 10(7) TCID50/g lung) and cotton rats
      (mean of 1.03 x 10(5) TCID50/g). Clinical symptoms consisting of breathing
      difficulties, ruffled fur, and weight loss were noted in mice only around the
      time of peak viral replication. Most significant pulmonary inflammatory changes
      and peak expression of macrophage inflammatory protein 1alpha, gamma interferon,
      and RANTES occurred at the time of maximal viral replication (day 5) in both
      models. Cellular infiltration occurred predominantly around and within alveoli
      and persisted for at least 21 days in mice, whereas it was more limited in time
      with more peribronchiolitis in cotton rats. Both animal models would be of great
      value in evaluating different therapeutic agents, as well as vaccine candidates
      against hMPV.

PMID- 15994784
TI  - High incidence of scrapie induced by repeated injections of subinfectious prion
      doses.
AB  - To clarify the mechanisms leading to the development of Creutzfeldt-Jakob disease
      in some recipients of pituitary-derived human growth hormone (hGH), we
      investigated the effects of repeated injections of low prion doses in mice. The
      injections were performed, as in hGH-treated children, by a peripheral route at
      short intervals and for an extended period. Twelve groups of 24 mice were
      intraperitoneally inoculated one, two, or five times per week for 200 days with 2
      x 10(-5) to 2 x 10(-8) dilutions of brain homogenate containing the mouse-adapted
      C506M3 scrapie strain. Sixteen control mice were injected once a week for 200
      days with a 2 x 10(-4) dilution of normal brain homogenate. Of mice injected in a
      single challenge with a scrapie inoculum of a 2 x 10(-4), 2 x 10(-5), or 2 x 10(
      6) dilution, 2/10, 1/10, and 0/10 animals developed scrapie, respectively.
      Control mice remained healthy. One hundred thirty-five of 135 mice injected with
      repeated prion doses of a 2 x 10(-5) or 2 x 10(-6) dilution succumbed to scrapie.
      Of mice injected with repeated scrapie doses of a 2 x 10(-7) or 2 x 10(-8)
      dilution, 52/59 and 38/67 animals died of scrapie, respectively. A high incidence
      of scrapie was observed in mice receiving repeated doses at low infectivity,
      whereas there was no disease in mice that were injected once with the same doses.
      Repeated injections of low prion doses thus constitute a risk for development of
      prion disease even if the same total dose inoculated in a single challenge does
      not induce the disease.

PMID- 15994785
TI  - In vivo self-interaction of nodavirus RNA replicase protein a revealed by
      fluorescence resonance energy transfer.
AB  - Flock house virus (FHV) is the best-characterized member of the Nodaviridae, a
      family of small, positive-strand RNA viruses. Unlike most RNA viruses, FHV
      encodes only a single polypeptide, protein A, that is required for RNA
      replication. Protein A contains a C-proximal RNA-dependent RNA polymerase domain
      and localizes via an N-terminal transmembrane domain to the outer mitochondrial
      membrane, where FHV RNA replication takes place in association with invaginations
      referred to as spherules. We demonstrate here that protein A self-interacts in
      vivo by using flow cytometric analysis of fluorescence resonance energy transfer
      (FRET), spectrofluorometric analysis of bioluminescence resonance energy
      transfer, and coimmunoprecipitation. Several nonoverlapping protein A sequences
      were able to independently direct protein-protein interaction, including an N
      terminal region previously shown to be sufficient for localization to the outer
      mitochondrial membrane (D. J. Miller and P. Ahlquist, J. Virol. 76:9856-9867,
      2000). Mutations in protein A that diminished FRET also diminished FHV RNA
      replication, a finding consistent with an important role for protein A self
      interaction in FHV RNA synthesis. Thus, the results imply that FHV protein A
      functions as a multimer rather than as a monomer at one or more steps in RNA
      replication.

PMID- 15994786
TI  - Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its
      association with chromatin.
AB  - The bovine papillomavirus E2 protein maintains and segregates the viral
      extrachromosomal genomes by tethering them to cellular mitotic chromosomes. E2
      interacts with a cellular bromodomain protein, Brd4, to mediate the segregation
      of viral genomes into daughter cells. Brd4 binds acetylated histones and has been
      observed to diffusely coat mitotic chromosomes in several cell types. In this
      study, we show that in mitotic C127 cells, Brd4 diffusely coated the condensed
      chromosomes. However, in the presence of the E2 protein, E2 and Brd4 colocalized
      in punctate dots that were randomly distributed over the chromosomes. A similar
      pattern of E2 and Brd4 colocalization on mitotic chromosomes was observed in CV-1
      cells, whereas only a faint chromosomal coating of Brd4 was detected in the
      absence of the E2 protein. Therefore, the viral E2 protein relocalizes and/or
      stabilizes the association of Brd4 with chromosomes in mitotic cells. The
      colocalization of E2 and Brd4 was also observed in interphase cells, indicating
      that this protein-protein interaction persists throughout the cell cycle. The
      interaction of E2 with Brd4 greatly stabilized the association of Brd4 with
      interphase chromatin. In both mitotic and interphase cells, this stabilization
      required a transcriptionally competent transactivation domain, but not the DNA
      binding function of the E2 protein. Thus, the E2 protein modulates the chromatin
      association of Brd4 during both interphase and mitosis. This study demonstrates
      that the segregation of papillomavirus genomes is not simply due to the passive
      hitchhiking of the E2/genome complex with a convenient cellular chromosomal
      protein.

PMID- 15994787
TI  - AIP1/Alix is a binding partner of Sendai virus C protein and facilitates virus
      budding.
AB  - The C protein, an accessory protein of Sendai virus (SeV), has anti-interferon
      capacity and suppresses viral RNA synthesis. In addition, it is thought that the
      C protein is involved in virus budding because of the low efficiency of release
      of progeny virions from C-knockout virus-infected cells and because of the
      requirement of the C protein for efficient release of virus-like particles. Here,
      we identified AIP1/Alix, a host protein involved in apoptosis and endosomal
      membrane trafficking, as an interacting partner of the C protein using a yeast
      two-hybrid system. The amino terminus of AIP1/Alix and the carboxyl terminus of
      the C protein are important for the interaction in mammalian cells. Mutant C
      proteins unable to bind AIP1/Alix failed to accelerate the release of virus-like
      particles from cells. Furthermore, overexpression of AIP1/Alix enhanced SeV
      budding from infected cells in a C-protein-dependent manner, while the release of
      nucleocapsid-free empty virions was also enhanced. Finally, AIP1/Alix depletion
      by small interfering RNA resulted in suppression of SeV budding. The results of
      this study suggest that AIP1/Alix plays a role in efficient SeV budding and that
      the SeV C protein facilitates virus budding through interaction with AIP1/Alix.

PMID- 15994788
TI  - Nairovirus RNA sequences expressed by a Semliki Forest virus replicon induce RNA
      interference in tick cells.
AB  - We report the successful infection of the cell line ISE6 derived from Ixodes
      scapularis tick embryos by the tick-borne Hazara virus (HAZV), a nairovirus in
      the family Bunyaviridae. Using a recombinant Semliki Forest alphavirus replicon
      that replicates in these cells, we were able to inhibit replication of HAZV, and
      we showed that this blockage is mediated by the replication of the Semliki Forest
      alphavirus replicon; the vector containing the HAZV nucleoprotein gene in sense
      or antisense orientation efficiently inhibited HAZV replication. Moreover,
      expression of a distantly related nucleoprotein gene from Crimean-Congo
      hemorrhagic fever nairovirus failed to induce HAZV silencing, indicating that the
      inhibition is sequence specific. The resistance of these cells to replicate HAZV
      correlated with the detection of specific RNase activity and 21- to 24-nucleotide
      long small interfering RNAs. Altogether, these results strongly suggest that
      pathogen-derived resistance can be established in the tick cells via a mechanism
      of RNA interference.

PMID- 15994789
TI  - Respiratory syncytial virus influences NF-kappaB-dependent gene expression
      through a novel pathway involving MAP3K14/NIK expression and nuclear complex
      formation with NF-kappaB2.
AB  - A member of the Paramyxoviridae family of RNA viruses, respiratory syncytial
      virus (RSV), is a leading cause of epidemic respiratory tract infection in
      children. In children, RSV primarily replicates in the airway mucosa, a process
      that alters epithelial cell chemokine expression, thereby inducing airway
      inflammation. We investigated the role of the mitogen-activated protein kinase
      kinase kinase 14/NF-kappaB-inducing kinase (NIK) in the activation of NF-kappaB
      dependent genes in alveolus-like A549 cells. RSV infection induces a time
      dependent increase of NIK mRNA and protein expression that peaks 12 to 24 h after
      viral exposure. Immunoprecipitation kinase assays indicate that NIK kinase
      activity is activated even more rapidly (within 6 h of RSV adsorption) associated
      with an endogenous approximately 50-kDa NF-kappaB2 substrate. Because NIK
      associates with IKKalpha to mediate processing of the 100-kDa NF-kappaB2
      precursor into its 52-kDa DNA binding isoform ("p52"), the effects of RSV on NIK
      complex formation with IKKalpha and NF-kappaB2 were determined by
      coimmunoprecipitation assay. We find that NIK, IKKalpha, and both 100 kDa- and 52
      kDa NF-kappaB2 isoforms strongly complex 15 h after exposure to RSV at times
      subsequent to NIK kinase activation. Western immunoblot and microaffinity DNA
      pull-down assays showed a parallel increase in nuclear translocation and DNA
      binding of the NF-kappaB2-Rel B complex. Interestingly, we make the novel
      observations that NIK also transiently translocates into the nucleus complexed
      with 52-kDa NF-kappaB2. Small interfering RNA-mediated NIK "knock-down" blocked
      RSV-inducible 52-kDa NF-kappaB2 processing and interfered with the early
      activation of a subset of NF-kappaB-dependent genes, indicating the importance of
      this activation pathway in the genomic NF-kappaB response to RSV. Together, these
      data indicate that RSV infection rapidly activates the noncanonical NF-kappaB
      activation pathway prior to the more potent canonical pathway activation. This
      appears to be through a novel mechanism involving induction of NIK kinase
      activity, expression, and nuclear translocation of a ternary complex with
      IKKalpha and processed NF-kappaB2.

PMID- 15994790
TI  - Low CD8 T-cell proliferative potential and high viral load limit the
      effectiveness of therapeutic vaccination.
AB  - Therapeutic vaccination has the potential to boost immune responses and enhance
      viral control during chronic infections. However, many therapeutic vaccination
      approaches have fallen short of expectations, and effective boosting of antiviral
      T-cell responses is not always observed. To examine these issues, we studied the
      impact of therapeutic vaccination, using a murine model of chronic infection with
      lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that
      therapeutic vaccination using a recombinant vaccinia virus expressing the LCMV
      GP33 CD8 T-cell epitope can be effective at accelerating viral control. However,
      mice with lower viral loads at the time of vaccination responded better to
      therapeutic vaccination than did those with high viral loads. Also, the
      proliferative potential of GP33-specific CD8 T cells from chronically infected
      mice was substantially lower than that of GP33-specific memory CD8 T cells from
      mice with immunity to LCMV, suggesting that poor T-cell expansion may be an
      important reason for suboptimal responses to therapeutic vaccination. Thus, our
      results highlight the potential positive effects of therapeutic vaccination on
      viral control during chronic infection but also provide evidence that a high
      viral load at the time of vaccination and the low proliferative potential of
      responding T cells are likely to limit the effectiveness of therapeutic
      vaccination.

PMID- 15994791
TI  - Human tripartite motif 5alpha domains responsible for retrovirus restriction
      activity and specificity.
AB  - The tripartite motif 5alpha protein (TRIM5alpha) is one of several factors
      expressed by mammalian cells that inhibit retrovirus replication. Human
      TRIM5alpha (huTRIM5alpha) inhibits infection by N-tropic murine leukemia virus (N
      MLV) but is inactive against human immunodeficiency virus type 1 (HIV-1).
      However, we show that replacement of a small segment in the carboxy-terminal
      B30.2/SPRY domain of huTRIM5alpha with its rhesus macaque counterpart
      (rhTRIM5alpha) endows it with the ability to potently inhibit HIV-1 infection.
      The B30.2/SPRY domain and an additional domain in huTRIM5alpha, comprising the
      amino-terminal RING and B-box components of the TRIM motif, are required for N
      MLV restriction activity, while the intervening coiled-coil domain is necessary
      and sufficient for huTRIM5alpha multimerization. Truncated huTRIM5alpha proteins
      that lack either or both the N-terminal RING/B-Box or the C-terminal B30.2/SPRY
      domain form heteromultimers with full-length huTRIM5alpha and are dominant
      inhibitors of its N-MLV restricting activity, suggesting that homomultimerization
      of intact huTRIM5alpha monomers is necessary for N-MLV restriction. However,
      localization in large cytoplasmic bodies is not required for inhibition of N-MLV
      by huTRIM5alpha or for inhibition of HIV-1 by chimeric or rhTRIM5alpha.

PMID- 15994792
TI  - The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1)
      group M, HIV-1 group O, and HIV-2 isolates.
AB  - The main (M) group of human immunodeficiency virus type 1 (HIV-1) is responsible
      for the global AIDS epidemic while HIV-1 group O (outlier) and HIV type 2 are
      endemic only in west and central Africa. The failure of HIV-2 and especially HIV
      1 group O to spread following the initial zoonotic jumps is not well understood.
      This study was designed to examine the relative replicative capacities between
      these human lentiviruses. A pairwise competition experiment was performed with
      peripheral blood mononuclear cells with eight HIV-2 isolates, 6 group O viruses,
      and 15 group M viruses of subtype A (2 viruses), B (5 viruses), C (4 viruses), D
      (2 viruses) and CRF01_AE (2 viruses). HIV-1 group M isolates of any subtype were
      typically 100-fold-more fit than group O or HIV-2 strains when competed in
      peripheral blood mononuclear cells from various humans. This order in replicative
      fitness was also observed when virus pairs were added to human dendritic cells
      and then cocultured with primary, quiescent T cells, which is the model for HIV-1
      transmission. These results suggest that reduced replicative and transmission
      fitness may be contributing to the low prevalence and limited geographical spread
      of HIV-2 and group O HIV-1 in the human population.

PMID- 15994793
TI  - Molecular epidemiology of simian immunodeficiency virus SIVsm in U.S. primate
      centers unravels the origin of SIVmac and SIVstm.
AB  - Retrospective molecular epidemiology was performed on samples from four sooty
      mangabey (SM) colonies in the United States to characterize simian
      immunodeficiency virus SIVsm diversity in SMs and to trace virus circulation
      among different primate centers (PCs) over the past 30 years. The following SIVsm
      sequences were collected from different monkeys: 55 SIVsm isolates from the
      Tulane PC sampled between 1984 and 2004, 10 SIVsm isolates from the Yerkes PC
      sampled in 2002, 7 SIVsm isolates from the New Iberia PC sampled between 1979 and
      1986, and 8 SIVsm isolates from the California PC sampled between 1975 and 1977.
      PCR and sequencing were done to characterize the gag, pol, and env gp36 genes.
      Phylogenetic analyses were correlated with the epidemiological data. Our analysis
      identified nine different divergent phylogenetic lineages that cocirculated in
      these four SM colonies in the Unites States in the past 30 years. Lineages 1 to 5
      have been identified previously. Two of the newly identified SIVsm lineages found
      in SMs are ancestral to SIVmac251/SIVmac239/SIVmne and SIVstm. We further
      identified the origin of these two macaque viruses in SMs from the California
      National Primate Research Center. The diversity of SIVsm isolates in PCs in the
      United States mirrors that of human immunodeficiency virus type 1 (HIV-1) group M
      subtypes and offers a model for the molecular epidemiology of HIV and a new
      approach to vaccine testing. The cocirculation of divergent SIVsm strains in PCs
      resulted in founder effects, superinfections, and recombinations. This large
      array of SIVsm strains showing the same magnitude of diversity as HIV-1 group M
      subtypes should be extremely useful for modeling the efficacy of vaccination
      strategies under the real-world conditions of HIV-1 diversity. The genetic
      variability of SIVsm strains among PCs may influence the diagnosis and monitoring
      of SIVsm infection and, consequently, may bias the results of pathogenesis
      studies.

PMID- 15994794
TI  - Changes in human immunodeficiency virus type 1 fitness and genetic diversity
      during disease progression.
AB  - This study examined the relationship between ex vivo human immunodeficiency virus
      type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1
      disease. Primary HIV-1 isolates from 10 patients at different time points were
      competed against control HIV-1 strains in peripheral blood mononuclear cell
      (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates
      sequentially gained fitness during disease at a significant rate that directly
      correlated with viral load and HIV-1 env C2V3 diversity. A loss in both fitness
      and viral diversity was observed upon the initiation of antiretroviral therapy. A
      possible relationship between genotype and phenotype (virus replication
      efficiency) is supported by the parallel increases in ex vivo fitness and viral
      diversity during disease, of which the correlation is largely based on specific
      V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher
      relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates,
      as determined by dual virus competitions in PBMC, but increases in fitness during
      disease were not solely powered by a gradual switch in coreceptor usage. These
      data provide in vivo evidence that increasing HIV-1 replication efficiency may be
      related to a concomitant increase in HIV-1 diversity, which in turn may be a
      determining factor in disease progression.

PMID- 15994795
TI  - Herpes simplex virus type 1 latency-associated transcript expression protects
      trigeminal ganglion neurons from apoptosis.
AB  - Upon infection of murine trigeminal ganglia with herpes simplex virus type 1 (HSV
      1), an immune response is initiated resulting in significant infiltration of CD8+
      T cells. Previous investigators have observed a lack of apoptosis in HSV-1
      trigeminal ganglia even in the presence of cytotoxic immune cells. To determine
      the role of the latency-associated transcript (LAT) in inhibiting apoptosis, we
      examined mice during acute and latent infection with HSV-1 (strain 17 or a LAT
      negative deletion mutant strain 17 N/H) by terminal deoxynucleotidyltransferase
      mediated dUTP-biotin nick end labeling (TUNEL) and fluorescence-activated cell
      sorting (FACS). FACS analysis revealed CD8+ T cells in the trigeminal ganglia by
      day 7, with more being present in 17- than 17 N/H-infected trigeminal ganglia
      (6.22% versus 3.5%) and a decrease in number through day 30 (2.7% to 1.2%). To
      detect apoptotic CD8+ T cells, sections were assayed by TUNEL and stained for
      CD8+ T cells. By day 7, approximately 10% of CD8+ T cells in both 17- and 17 N/H
      infected trigeminal ganglia had undergone apoptosis. By day 30, 58% and 74% of
      all T cells had undergone apoptosis in 17- and 17 N/H-infected trigeminal
      ganglia, respectively. Furthermore, no HSV strain 17-infected trigeminal ganglion
      neurons were apoptotic, but 0.087% of 17deltaSty and 0.98% of 17 N/H-infected
      neurons were apoptotic. We conclude that the antiapoptotic effect of LAT appears
      to require the LAT promoter, with most of the antiapoptotic effect mapping within
      the StyI (+447) to the HpaI (+1667) region and a minor contribution from the
      upstream StyI (+76) to StyI (+447) region.

PMID- 15994796
TI  - Low human immunodeficiency virus envelope diversity correlates with low in vitro
      replication capacity and predicts spontaneous control of plasma viremia after
      treatment interruptions.
AB  - Genetic diversity of viral isolates in human immunodeficiency virus (HIV)
      infected individuals varies substantially. However, it remains unclear whether
      HIV-related disease progresses more rapidly in patients harboring virus swarms
      with low or high diversity and, in the same context, whether high or low
      diversity is required to induce potent humoral and cellular immune responses. To
      explore whether viral diversity predicts virologic control, we studied HIV
      infected patients who received antiretroviral therapy (ART) for years before
      undergoing structured treatment interruptions (STI). Viral diversity before
      initiation of ART and the ability of the patients to contain viremia after STI
      and final cessation of treatment was evaluated. Seven out of 21 patients
      contained plasma viremia at low levels after the final treatment cessation.
      Clonal sequences encompassing the envelope C2V3C3 domain derived from plasma
      prior to treatment, exhibited significantly lower diversity in these patients
      compared to those derived from patients with poor control of viremia. Viral
      diversity pre-ART correlated with the viral replication capacity of rebounding
      virus isolates during STI. Neutralizing antibody activity against autologous
      virus was significantly higher in patients who controlled viremia and was
      associated with lower pretreatment diversity. No such association was found with
      binding antibodies directed to gp120. In summary, lower pretreatment viral
      diversity was associated with spontaneous control of viremia, reduced viral
      replication capacity and higher neutralizing antibody titers, suggesting a link
      between viral diversity, replication capacity, and neutralizing antibody
      activity.

PMID- 15994797
TI  - Heterologous late-domain sequences have various abilities to promote budding of
      human immunodeficiency virus type 1.
AB  - Retroviral late (L) domains present within Gag act in conjunction with cellular
      proteins to efficiently release virions from the surface of the cell. Three
      different critical core sequences have been identified as required elements for L
      domain function: PPPY, PTAP (also PSAP), and YPDL, with different retroviruses
      utilizing one or two of these core sequences. The human immunodeficiency virus
      type 1 (HIV-1) L domain is centered around a PTAP sequence in the p6 region of
      Gag. To assess the ability of heterologous L-domain sequences to be functionally
      interchanged for those in full-length HIV-1, we produced a series of constructs
      that replaced PTAP-containing p6(Gag) sequences with those of PPPY- or YPDL-based
      L domains. While previous studies had found that L domains are interchangeable in
      other retroviruses, most of the sequences introduced into p6(Gag) failed to
      substitute for PTAP-mediated L-domain function. One exception was the 11-amino
      acid p2b sequence of Rous sarcoma virus (RSV) Gag, which could fully restore HIV
      1 budding, while a PPPPY sequence exchange alone did not. This suggests that the
      RSV L domain consists of more than simply its core L-domain sequence. The HIV-p2b
      chimera was as infectious as the wild type, produced normal virions, and was
      sensitive to proteasome inhibitors. These results show that L-domain sequences
      are not necessarily interchangeable. Thus, HIV-1 Gag might have a more stringent
      requirement for L-domain function than the other retroviruses previously studied.

PMID- 15994798
TI  - Structural and functional analysis of the cis-acting elements required for plus
      strand RNA synthesis of Bamboo mosaic virus.
AB  - Bamboo mosaic virus (BaMV) has a single-stranded positive-sense RNA genome. The
      secondary structure of the 3'-terminal sequence of the minus-strand RNA has been
      predicted by MFOLD and confirmed by enzymatic structural probing to consist of a
      large, stable stem-loop and a small, unstable stem-loop. To identify the promoter
      for plus-strand RNA synthesis in this region, transcripts of 39, 77, and 173
      nucleotides (Ba-39, Ba-77, and Ba-173, respectively) derived from the 3' terminus
      of the minus-strand RNA were examined by an in vitro RNA-dependent RNA polymerase
      assay for the ability to direct RNA synthesis. Ba-77 and Ba-39 appeared to direct
      the RNA synthesis efficiently, while Ba-173 failed. Ba-77/delta5, with a deletion
      of the 3'-terminal UUUUC sequence in Ba-77, directed the RNA synthesis only to 7%
      that of Ba-77. However, Ba-77/delta16 and Ba-77/delta31, with longer deletions
      but preserving the terminal UUUUC sequence of Ba-77, restored the template
      activity to about 60% that of the wild type. Moreover, mutations that changed the
      sequence in the stem of the large stem-loop interfered with the efficiency of RNA
      synthesis and RNA accumulation in vivo. The mutant with an internal deletion in
      the region between the terminal UUUUC sequence and the large stem-loop reduced
      the viral RNA accumulation in protoplasts, but mutants with insertions did not.
      Taken together, these results suggest that three cis-acting elements in the 3'
      end of the minus-strand RNA, namely, the terminal UUUUC sequence, the sequence in
      the large stem-loop, and the distance between these two regions, are involved in
      modulating the efficiency of BaMV plus-strand viral RNA synthesis.

PMID- 15994799
TI  - Plant virus HC-Pro is a determinant of eriophyid mite transmission.
AB  - The eriophyid mite transmitted Wheat streak mosaic virus (WSMV; genus
      Tritimovirus, family Potyviridae) shares a common genome organization with aphid
      transmitted species of the genus Potyvirus. Although both tritimoviruses and
      potyviruses encode helper component-proteinase (HC-Pro) homologues (required for
      nonpersistent aphid transmission of potyviruses), sequence conservation is low
      (amino acid identity, approximately 16%), and a role for HC-Pro in semipersistent
      transmission of WSMV by the wheat curl mite (Aceria tosichella [Keifer]) has not
      been investigated. Wheat curl mite transmissibility was abolished by replacement
      of WSMV HC-Pro with homologues of an aphid transmitted potyvirus (Turnip mosaic
      virus), a rymovirus (Agropyron mosaic virus) vectored by a different eriophyid
      mite, or a closely related tritimovirus (Oat necrotic mottle virus; ONMV) with no
      known vector. In contrast, both WSMV-Sidney 81 and a chimeric WSMV genome bearing
      HC-Pro of a divergent strain (WSMV-El Batan 3; 86% amino acid sequence identity)
      were efficiently transmitted by A. tosichella. Replacing portions of WSMV-Sidney
      81 HC-Pro with the corresponding regions from ONMV showed that determinants of
      wheat curl mite transmission map to the 5'-proximal half of HC-Pro. WSMV genomes
      bearing HC-Pro of heterologous species retained the ability to form virions,
      indicating that loss of vector transmissibility was not a result of failure to
      encapsidate. Although titer in systemically infected leaves was reduced for all
      chimeric genomes relative to WSMV-Sidney 81, titer was not correlated with loss
      of vector transmissibility. Collectively, these results demonstrate for the first
      time that HC-Pro is required for virus transmission by a vector other than
      aphids.

PMID- 15994800
TI  - Novel human monoclonal antibody combination effectively neutralizing natural
      rabies virus variants and individual in vitro escape mutants.
AB  - The need to replace rabies immune globulin (RIG) as an essential component of
      rabies postexposure prophylaxis is widely acknowledged. We set out to discover a
      unique combination of human monoclonal antibodies (MAbs) able to replace RIG.
      Stringent criteria concerning neutralizing potency, affinity, breadth of
      neutralization, and coverage of natural rabies virus (RV) isolates and in vitro
      escape mutants were set for each individual antibody, and the complementarities
      of the two MAbs were defined at the onset. First, we identified and characterized
      one human MAb (CR57) with high in vitro and in vivo neutralizing potency and a
      broad neutralization spectrum. The linear antibody binding site was mapped on the
      RV glycoprotein as antigenic site I by characterizing CR57 escape mutants.
      Secondly, we selected using phage display a complementing antibody (CR4098) that
      recognized a distinct, nonoverlapping epitope (antigenic site III), showed
      similar neutralizing potency and breadth as CR57, and neutralized CR57 escape
      mutants. Reciprocally, CR57 neutralized RV variants escaping CR4098. Analysis of
      glycoprotein sequences of natural RV isolates revealed that the majority of
      strains contain both intact epitopes, and the few remaining strains contain at
      least one of the two. In vitro exposure of RV to the combination of CR57 and
      CR4098 yielded no escape mutants. In conclusion, a novel combination of human
      MAbs was discovered suitable to replace RIG.

PMID- 15994801
TI  - The V1, V2, and V3 regions of the human immunodeficiency virus type 1 envelope
      differentially affect the viral phenotype in an isolate-dependent manner.
AB  - It is well documented that removal of the V1V2 region or of the V2 loop alone
      from the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) or
      simian immunodeficiency virus (SIV) increases the susceptibility of these viruses
      to neutralization by antibodies. The specific role of the V1 loop in defining the
      neutralization susceptibility of HIV is, however, not well documented. Our
      current studies indicate that although the V1V2 region is a global modulator of
      the HIV-1 neutralization susceptibility, the individual roles the V1 and V2 loops
      have in defining the neutralization susceptibility profile of HIV-1 differ and in
      some cases are opposite. While deletion of the V2 loop renders the virus more
      susceptible to neutralization by antibodies that recognize diverse epitopes, in
      particular certain ones located in the CD4 binding site and the V3 loop, deletion
      of the V1 loop renders the virus refractory to neutralization, especially by
      antibodies that recognize CD4-induced epitopes and certain CD4-site binding
      antibodies. Our current studies also indicate that the relative involvement of
      the V2 loop of the HIV-1 envelope during virus-cell entry appears to be envelope
      background dependent. As a result, although deletion of the V2 loop from the
      clade B, R5-tropic SF162 HIV-1 virus resulted in a virus that was replication
      competent, the same modification introduced on the background of two other R5
      tropic isolates, SF128A (clade B) or SF170 (clade A), abrogated the ability of
      these envelopes to mediate virus-cell entry.

PMID- 15994802
TI  - Defective replication in human immunodeficiency virus type 1 when non-primers are
      used for reverse transcription.
AB  - tRNA(3Lys), the primer for reverse transcriptase in human immunodeficiency virus
      type 1 (HIV-1), anneals to the primer binding site (PBS) in HIV-1 RNA. It has
      been shown that altering the PBS and U5 regions upstream of the PBS in HIV-1 so
      as to be complementary to sequences in tRNA(Met) or tRNA(His) will allow these
      tRNA species to be stably used as primers for reverse transcription. We have
      examined the replication of these mutant viruses in Sup-T1 cells. When Sup-T1
      cells are infected by cocultivation with HIV-1-transfected 293T cells, viruses
      using tRNA(His) or tRNA(Met) are produced at rates that are approximately 1/10 or
      1/100, respectively, of rates for wild-type virions that use tRNA(3Lys). When Sup
      T1 cells are directly infected with equal amounts of these different viruses
      isolated from the culture supernatant of transfected 293T cells, virions using
      tRNA(Met) are produced at 1/100 the rate of wild-type viruses, and production of
      virions using tRNA(His) is not detected. Both wild-type and mutant virions
      selectively package tRNA(Lys) only, and examination of the ability of total viral
      RNA to prime reverse transcription in vitro indicates a >80% reduction in the
      annealing of tRNA(His) or tRNA(Met) to the mutant viral RNAs. PCR analysis of
      which of the three primer tRNAs is used indicates that only tRNA(3Lys) is
      detected as primer in wild-type virions and only tRNA(His) is detected as primer
      in virions containing a PBS complementary to tRNA(His), while the mutant viruses
      containing a PBS complementary to tRNA(Met) use both tRNA(Met) and tRNA(1,2Lys)
      as primer tRNAs.

PMID- 15994803
TI  - Mutations in the putative zinc-binding motif of UL52 demonstrate a complex
      interdependence between the UL5 and UL52 subunits of the human herpes simplex
      virus type 1 helicase/primase complex.
AB  - Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase-primase
      (UL5/8/52) complex. UL5 contains seven motifs found in helicase superfamily 1,
      and UL52 contains conserved motifs found in primases. The contributions of each
      subunit to the biochemical activities of the complex, however, remain unclear. We
      have previously demonstrated that a mutation in the putative zinc finger at UL52
      C terminus abrogates not only primase but also ATPase, helicase, and DNA-binding
      activities of a UL5/UL52 subcomplex, indicating a complex interdependence between
      the two subunits. To test this hypothesis and to further investigate the role of
      the zinc finger in the enzymatic activities of the helicase-primase, a series of
      mutations were constructed in this motif. They differed in their ability to
      complement a UL52 null virus: totally defective, partial complementation, and
      potentiating. In this study, four of these mutants were studied biochemically
      after expression and purification from insect cells infected with recombinant
      baculoviruses. All mutants show greatly reduced primase activity. Complementation
      defective mutants exhibited severe defects in ATPase, helicase, and DNA-binding
      activities. Partially complementing mutants displayed intermediate levels of
      these activities, except that one showed a wild-type level of helicase activity.
      These data suggest that the UL52 zinc finger motif plays an important role in the
      activities of the helicase-primase complex. The observation that mutations in
      UL52 affected helicase, ATPase, and DNA-binding activities indicates that UL52
      binding to DNA via the zinc finger may be necessary for loading UL5.
      Alternatively, UL5 and UL52 may share a DNA-binding interface.

PMID- 15994804
TI  - Constituents of SH1, a novel lipid-containing virus infecting the halophilic
      euryarchaeon Haloarcula hispanica.
AB  - Recent studies have indicated that a number of bacterial and eukaryotic viruses
      that share a common architectural principle are related, leading to the proposal
      of an early common ancestor. A prediction of this model would be the discovery of
      similar viruses that infect archaeal hosts. Our main interest lies in icosahedral
      double-stranded DNA (dsDNA) viruses with an internal membrane, and we now extend
      our studies to include viruses infecting archaeal hosts. While the number of
      sequenced archaeal viruses is increasing, very little sequence similarity has
      been detected between bacterial and eukaryotic viruses. In this investigation we
      rigorously show that SH1, an icosahedral dsDNA virus infecting Haloarcula
      hispanica, possesses lipid structural components that are selectively acquired
      from the host pool. We also determined the sequence of the 31-kb SH1 genome and
      positively identified genes for 11 structural proteins, with putative
      identification of three additional proteins. The SH1 genome is unique and, except
      for a few open reading frames, shows no detectable similarity to other published
      sequences, but the overall structure of the SH1 virion and its linear genome with
      inverted terminal repeats is reminiscent of lipid-containing dsDNA bacteriophages
      like PRD1.

PMID- 15994805
TI  - Contributions of the viral genetic background and a single amino acid
      substitution in an immunodominant CD8+ T-cell epitope to murine coronavirus
      neurovirulence.
AB  - The immunodominant CD8+ T-cell epitope of a highly neurovirulent strain of mouse
      hepatitis virus (MHV), JHM, is thought to be essential for protection against
      virus persistence within the central nervous system. To test whether abrogation
      of this H-2Db-restricted epitope, located within the spike glycoprotein at
      residues S510 to 518 (S510), resulted in delayed virus clearance and/or virus
      persistence we selected isogenic recombinants which express either the wild-type
      JHM spike protein (RJHM) or spike containing the N514S mutation (RJHM(N514S)),
      which abrogates the response to S510. In contrast to observations in suckling
      mice in which viruses encoding inactivating mutations within the S510 epitope
      (epitope escape mutants) were associated with persistent virus and increased
      neurovirulence (Pewe et al., J Virol. 72:5912-5918, 1998), RJHM(N514S) was not
      more virulent than the parental, RJHM, in 4-week-old C57BL/6 (H-2b) mice after
      intracranial injection. Recombinant viruses expressing the JHM spike, wild type
      or encoding the N514S substitution, were also selected in which background genes
      were derived from the neuroattenuated A59 strain of MHV. Whereas recombinants
      expressing the wild-type JHM spike (SJHM/RA59) were highly neurovirulent, A59
      recombinants containing the N514S mutation (SJHM(N514S)/RA59) were attenuated,
      replicated less efficiently, and exhibited reduced virus spread in the brain at 5
      days postinfection (peak of infectious virus titers in the central nervous
      system) compared to parental virus encoding wild-type spike. Virulence assays in
      BALB/c mice (H-2d), which do not recognize the S510 epitope, revealed that
      attenuation of the epitope escape mutants was not due to the loss of a pathogenic
      immune response directed against the S510 epitope. Thus, an intact immunodominant
      S510 epitope is not essential for virus clearance from the CNS, the S510
      inactivating mutation results in decreased virulence in weanling mice but not in
      suckling mice, suggesting that specific host conditions are required for epitope
      escape mutants to display increased virulence, and the N514S mutation causes
      increased attenuation in the context of A59 background genes, demonstrating that
      genes other than that for the spike are also important in determining
      neurovirulence.

PMID- 15994806
TI  - Essential and nonessential elements in the 3' nontranslated region of Bovine
      viral diarrhea virus.
AB  - The 3' nontranslated region (NTR) of the pestivirus Bovine viral diarrhea virus
      (BVDV), a close relative of human Hepatitis C virus, consists of three stem-loops
      which are separated by two single-stranded regions. As in other positive-stranded
      RNA viruses, the 3' NTR of pestiviruses is involved in crucial processes of the
      viral life cycle. While several studies characterized cis-acting elements within
      the 3' NTR of a BVDV replicon, there are no studies addressing the significance
      of these elements in the context of a replicating virus. To examine the
      functional importance of 3' NTR elements, a set of 4-base deletions and deletions
      of each of the three stem-loops were introduced into an infectious BVDV cDNA
      clone. Emerging mutant viruses were characterized with regard to plaque
      phenotype, growth kinetics, and synthesis of viral RNA. The results indicated
      that presence of stem-loop (SL) I and the 3'-terminal part of the single-stranded
      region between stem-loops I and II are indispensable for pestiviral replication.
      In contrast, deletions within SL II and SL III as well as absence of either SL II
      or SL III still allowed efficient viral replication; however, a mutant RNA
      lacking both SL II and SL III was not infectious. The results of this study
      provide a detailed map of the essential and nonessential elements within the 3'
      NTR of BVDV and contribute to our understanding of sequence and structural
      elements important for efficient viral replication of pestiviruses in natural
      host cells.

PMID- 15994807
TI  - Envelope glycoprotein mutations mediate equine amplification and virulence of
      epizootic venezuelan equine encephalitis virus.
AB  - Epidemics of Venezuelan equine encephalitis (VEE) result from high-titer equine
      viremia of IAB and IC subtype viruses that mediate increased mosquito
      transmission and spillover to humans. Previous genetic studies suggest that
      mutations in the E2 envelope glycoprotein allow relatively viremia-incompetent,
      enzootic subtype ID strains to adapt for equine replication, leading to VEE
      emergence. To test this hypothesis directly, chimeric VEEV strains containing the
      genetic backbone of enzootic subtype ID strains and the partial envelope
      glycoprotein genes of epizootic subtype IC and IAB strains, as well as reciprocal
      chimeras, were used for experimental infections of horses. Insertion of envelope
      genes from two different, closely related enzootic subtype ID strains into the
      epizootic backbones resulted in attenuation, demonstrating that the epizootic
      envelope genes are necessary for the equine-virulent and viremia-competent
      phenotypes. The partial epizootic envelope genes introduced into an enzootic ID
      backbone were sufficient to generate the virulent, viremia-competent equine
      phenotype. These results indicate that a small number of envelope gene mutations
      can generate an equine amplification-competent, epizootic VEEV from an enzootic
      progenitor and underscore the limitations of small animal models for evaluating
      and predicting the epizootic phenotype.

PMID- 15994808
TI  - Analysis of human immunodeficiency virus type 1 Gag ubiquitination.
AB  - Ubiquitin is important for the release of human immunodeficiency virus type 1
      (HIV-1) and several other retroviruses, but the functional significance of Gag
      ubiquitination is unknown. To address this problem, we decided to analyze Gag
      ubiquitination in detail. A low percentage of the HIV-1 p6 protein has previously
      been shown to be ubiquitinated, and published mutagenesis data suggested that Gag
      ubiquitination is largely lost upon mutation of the two lysine residues in p6. In
      this study, we show that Gag proteins lacking the p6 domain or the two lysine
      residues within p6 are ubiquitinated at levels comparable to those of the wild
      type Gag protein. We detected monoubiquitinated forms of the matrix (MA), capsid
      (CA), and nucleocapsid (NC) proteins in mature virus preparations. Protease
      digestion of Gag polyproteins extracted from immature virions indicated that
      ubiquitinated MA, CA, and possibly NC are as abundant as ubiquitinated p6. The
      HIV-1 late-domain motifs PTAP and LRSLF were not required for Gag ubiquitination,
      and mutation of the PTAP motif even resulted in an increase in the amount of Gag
      Ub conjugates detected. Finally, at steady state, ubiquitinated Gag proteins were
      not enriched in either membrane-associated or virus-derived Gag fractions. In
      summary, these results indicate that HIV-1 Gag can be monoubiquitinated in all
      domains and that ubiquitination of lysine residues outside p6 may thus contribute
      to viral release and/or infectivity.

PMID- 15994809
TI  - Compartmentalization of hepatitis C virus quasispecies in blood mononuclear cells
      of patients with mixed cryoglobulinemic syndrome.
AB  - The aim of this study was to investigate the quasispecies heterogeneity of
      hepatitis C virus (HCV) in the plasma, cryoprecipitate, and peripheral
      lymphocytes of chronically infected HCV patients with mixed cryoglobulinemia
      (MC). We studied 360 clones from 10 HCV-positive patients with MC and 8 age-,
      gender- and HCV genotype-matched subjects with chronic HCV infection but without
      MC. A partial nucleotide sequence encompassing the E1/E2 region, including
      hypervariable region 1 (HVR1), was amplified and cloned from plasma,
      cryoprecipitates, and peripheral blood mononuclear cells (PBMC), and the genetic
      diversity and complexity and synonymous and nonsynonymous substitution rates were
      determined. Heterogeneous selection pressure at codon sites was evaluated.
      Compartmentalization was estimated by phylogenetic and phenetic (Mantel's test)
      approaches. The patients with MC had 3.3 times lower nonsynonymous substitution
      rates (1.7 versus 5.7 substitutions/100 sites). Among the subjects with HCV
      genotype 1, the MC patients had significantly less complexity than the controls,
      whereas the diversity and complexity were similar in the genotype 2 patients and
      controls. Site-specific selection analysis confirmed the low frequency of MC
      patients showing positive selection. There was a significant correlation between
      positive selection and the infecting HCV genotype. The quasispecies were less
      heterogeneous in PBMC than in plasma. Significant compartmentalization of HCV
      quasispecies was observed in the PBMC of four of nine subjects (three with MC)
      and seven of nine cryoprecipitates. In one subject with MC, we detected a 5-amino
      acid insertion at codons 385 to 389 of HVR1. Our results suggest reduced
      quasispecies heterogeneity in MC patients that is related to a low selection
      pressure which is probably due to an impaired immune response, the HCV genotype,
      and/or the duration of the infection. The frequent HCV quasispecies
      compartmentalization in patients' PBMC suggests a possible pathogenetic
      significance.

PMID- 15994810
TI  - Genetic variability and molecular evolution of the human respiratory syncytial
      virus subgroup B attachment G protein.
AB  - Human respiratory syncytial virus (HRSV) is the most important cause of acute
      respiratory disease in infants. Two major subgroups (A and B) have been
      identified based on antigenic differences in the attachment G protein. Antigenic
      variation between and within the subgroups may contribute to reinfections with
      these viruses by evading the host immune responses. To investigate the
      circulation patterns and mechanisms by which HRSV-B viruses evolve, we analyzed
      the G protein genetic variability of subgroup B sequences isolated over a 45-year
      period, including 196 Belgian strains obtained over 22 epidemic seasons (1982 to
      2004). Our study revealed that the HRSV-B evolutionary rate (1.95 x 10(-3)
      nucleotide substitutions/site/year) is similar to that previously estimated for
      HRSV-A (1.83 x 10(-3) nucleotide substitutions/site/year). However, natural HRSV
      B isolates appear to accommodate more drastic changes in their attachment G
      proteins. The most recent common ancestor of the currently circulating subgroup B
      strains was estimated to date back to around the year 1949. The divergence
      between the two major subgroups was calculated to have occurred approximately 350
      years ago. Furthermore, we have identified 12 positively selected sites in the G
      protein ectodomain, suggesting that immune-driven selective pressure operates in
      certain codon positions. HRSV-A and -B strains have similar phylodynamic
      patterns: both subgroups are characterized by global spatiotemporal strain
      dynamics, where the high infectiousness of HRSV permits the rapid geographic
      spread of novel strain variants.

PMID- 15994811
TI  - Suppressors of a host range mutation in the rabbitpox virus serpin SPI-1 map to
      proteins essential for viral DNA replication.
AB  - The orthopoxvirus serpin SPI-1 is an intracellular serine protease inhibitor that
      is active against cathepsin G in vitro. Rabbitpox virus (RPV) mutants with
      deletions of the SPI-1 gene grow on monkey kidney cells (CV-1) but do not plaque
      on normally permissive human lung carcinoma cells (A549). This reduced-host-range
      (hr) phenotype suggests that SPI-1 may interact with cellular and/or other viral
      proteins. We devised a genetic screen for suppressors of SPI-1 hr mutations by
      first introducing a mutation into SPI-1 (T309R) at residue P14 of the serpin
      reactive center loop. The SPI-1 T309R serpin is inactive as a protease inhibitor
      in vitro. Introduction of the mutation into RPV leads to the same restricted hr
      phenotype as deletion of the SPI-1 gene. Second-site suppressors were selected by
      restoration of growth of the RPV SPI-1 T309R hr mutant on A549 cells. Both
      intragenic and extragenic suppressors of the T309R mutation were identified. One
      novel intragenic suppressor mutation, T309C, restored protease inhibition by SPI
      1 in vitro. Extragenic suppressor mutations were mapped by a new procedure
      utilizing overlapping PCR products encompassing the entire genome in conjunction
      with marker rescue. One suppressor mutation, which also rendered the virus
      temperature sensitive for growth, mapped to the DNA polymerase gene (E9L).
      Several other suppressors mapped to gene D5R, an NTPase required for DNA
      replication. These results unexpectedly suggest that the host range function of
      SPI-1 may be associated with viral DNA replication by an as yet unknown
      mechanism.

PMID- 15994812
TI  - Regulation of human immunodeficiency virus type 1 gene expression by clade
      specific Tat proteins.
AB  - The major group of human immunodeficiency virus type 1 (HIV-1) strains that
      comprise the current global pandemic have diversified during their worldwide
      spread into at least 10 distinct subtypes, or clades. Subtype C predominates in
      sub-Saharan Africa and is responsible for the majority of worldwide HIV-1
      infections, subtype B predominates in North America and Europe, and subtype E is
      prevalent in Southeast Asia. Significant amino acid variations have been observed
      among the clade-specific Tat proteins. For the present study, we examined clade
      specific interactions between Tat, transactivation-responsive (TAR) element, and
      P-TEFb proteins and how these interactions may modulate the efficiency of HIV-1
      transcription. Clade-specific Tat proteins significantly modified viral gene
      expression. Tat proteins derived from HIV-1 clades C and E were strong
      transactivators of long terminal repeat (LTR) activity; Tat E also had a longer
      half-life than the other Tat proteins and interacted more efficiently with the
      stem-loop TAR element. Chimeric Tat proteins harboring the Tat E activation
      domain were strong transactivators of LTR expression. While Tat B, C, and E were
      able to rescue a Tat-defective HIV-1 proviral clone, Tat E was significantly more
      efficient at rescue than Tat C, possibly due to the relative stability of the Tat
      protein. Swapping the activation domains of Tat B, C, and E identified the cyclin
      T1 association domain as a critical determinant of the transactivation efficiency
      and of Tat-defective HIV-1 provirus rescue.

PMID- 15994813
TI  - Mannose binding lectin genotypes influence recovery from hepatitis B virus
      infection.
AB  - Mannose binding lectin (MBL) is a central component of the innate immune response
      and thus may be important for determining hepatitis B virus (HBV) persistence.
      Since single-nucleotide polymorphisms (SNPs) in the gene encoding MBL (mbl2)
      alter the level of functional MBL, we hypothesized that mbl2 genotypes are a
      determinant of HBV persistence or recovery from viral infection. We tested this
      hypothesis by using a nested case control design with 189 persons with HBV
      persistence matched to 338 individuals who had naturally recovered from HBV
      infection. We determined genotypes of two promoter and three exon 1 SNPs in mbl2
      and grouped these genotypes according to the amount of functional MBL production.
      We found that the promoter SNP -221C, which leads to deficient MBL production,
      was more common in those subjects with viral persistence (odds ratio [OR], 1.38;
      95% confidence interval [CI], 1.01 to 1.89; P = 0.04). Those subjects homozygous
      for the combination of promoter and exon 1 genotypes associated with the highest
      amount of functional MBL had significantly increased odds of recovery from
      infection (OR, 0.55; 95% CI, 0.37 to 0.84; P = 0.005). Conversely, those
      homozygous for the combination of promoter and exon 1 genotypes which produce the
      lowest amount of functional MBL were more likely to have viral persistence (OR,
      1.76; 95% CI, 1.02 to 3.01; P = 0.04). These data are consistent with the
      hypothesis that functional MBL plays a central role in the pathogenesis of acute
      hepatitis B.

PMID- 15994814
TI  - In vitro suppression of human immunodeficiency virus type 1 replication by
      measles virus.
AB  - During the acute phase of measles, human immunodeficiency virus type 1 (HIV-1)
      infected children have a transient, but dramatic, decrease in plasma HIV-1 RNA
      levels (W. J. Moss, J. J. Ryon, M. Monze, F. Cutts, T. C. Quinn, and D. E.
      Griffin, J. Infect. Dis. 185:1035-1042, 2002). To determine the mechanism(s) by
      which coinfection with measles virus (MV) decreases HIV-1 replication, we
      established an in vitro culture system that reproduces this effect. The addition
      of MV to CCR5- or CXCR4-tropic HIV-1-infected human peripheral blood mononuclear
      cells (PBMCs) decreased HIV-1 p24 antigen production in a dose-dependent manner.
      This decrease occurred with the addition of MV before or after HIV-1. The
      inhibition of HIV-1 p24 antigen production was decreased when UV-inactivated MV
      or virus-free supernatant fluid from MV-infected PBMCs was used. Inhibition was
      not due to increased production of chemokines known to block coreceptor usage by
      HIV-1, a decrease in the percentage of CD4+ T cells, or a decrease in chemokine
      receptor expression by CD4+ T cells. Viability of PBMCs was decreased only 10 to
      20% by MV coinfection; however, lymphocyte proliferation was decreased by 60 to
      90% and correlated with decreased production of p24 antigen. These studies showed
      that an in vitro system of coinfected PBMCs could be used to dissect the
      mechanism(s) by which MV suppresses HIV-1 replication in coinfected children and
      suggest that inhibition of lymphocyte proliferation by MV may play a role in the
      suppression of HIV-1 p24 antigen production.

PMID- 15994815
TI  - Infectious pancreatic necrosis virus VP5 is dispensable for virulence and
      persistence.
AB  - Infectious pancreatic necrosis virus (IPNV) is the causative agent of infectious
      pancreatic necrosis (IPN) disease in salmonid fish. Recent studies have revealed
      variation in virulence between isolates of the Sp serotype, associated with
      certain residues of the structural protein VP2. The isolates are also highly
      heterogenic in the coding region of the nonstructural VP5 protein. To study the
      involvement of this protein in the pathogenesis of disease, we generated three
      recombinant VP5 mutant viruses using reverse genetics. The "wild-type"
      recombinant NVI15 (rNVI15) virus is virulent, having a premature stop codon at
      nucleotide position 427, putatively encoding a truncated 12-kDa VP5 protein,
      whereas rNVI15-15K virus encodes a 15-kDa protein. Recombinant rNVI15-deltaVP5
      virus contains a mutation in the initiation codon of the VP5 gene that ablates
      the expression of VP5. Atlantic salmon postsmolts were challenged to study the
      virulence characteristics of the recovered viruses in vivo. The role of VP5 in
      persistent infection was investigated by challenging Atlantic salmon fry with the
      recovered viruses, as well as with the low-virulence field strain Sp103 and a
      naturally occurring VP5-deficient mutant of Sp103. The results show that VP5 is
      not required for viral replication in vivo, and its absence does not alter the
      virulence characteristics of the virus or the establishment of persistent IPNV
      infection.

PMID- 15994816
TI  - Propagation and dissemination of infection after vaginal transmission of simian
      immunodeficiency virus.
AB  - In the current global AIDS pandemic, more than half of new human immunodeficiency
      virus type 1 (HIV-1) infections are acquired by women through intravaginal HIV
      exposure. For this study, we explored pathogenesis issues relevant to the
      development of effective vaccines to prevent infection by this route, using an
      animal model in which female rhesus macaques were exposed intravaginally to a
      high dose of simian immunodeficiency virus (SIV). We examined in detail the
      events that transpire from hours to a few days after intravaginal SIV exposure
      through week 4 to provide a framework for understanding the propagation,
      dissemination, and establishment of infection in lymphatic tissues (LTs) during
      the acute stage of infection. We show that the mucosal barrier greatly limits the
      infection of cervicovaginal tissues, and thus the initial founder populations of
      infected cells are small. While there was evidence of rapid dissemination to
      distal sites, we also show that continuous seeding from an expanding source of
      production at the portal of entry is likely critical for the later establishment
      of a productive infection throughout the systemic LTs. The initially small
      founder populations and dependence on continuous seeding to establish a
      productive infection in systemic LTs define a small window of maximum
      vulnerability for the virus in which there is an opportunity for the host,
      vaccines, or other interventions to prevent or control infection.

PMID- 15994817
TI  - CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal
      exposure to simian immunodeficiency virus: too late and too little.
AB  - In the acute stage of infection following sexual transmission of human
      immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus
      specific CD8+ T-lymphocyte responses partially control but do not eradicate
      infection from the lymphatic tissues (LTs) or prevent the particularly massive
      depletion of CD4+ T lymphocytes in gut-associated lymphatic tissue (GALT). We
      explored hypothetical explanations for this failure to clear infection and
      prevent CD4+ T-lymphocyte loss in the SIV/rhesus macaque model of intravaginal
      transmission. We examined the relationship between the timing and magnitude of
      the CD8+ T-lymphocyte response to immunodominant SIV epitopes and viral
      replication, and we show first that the failure to contain infection is not
      because the female reproductive tract is a poor inductive site. We documented
      robust responses in cervicovaginal tissues and uterus, but only several days
      after the peak of virus production. Second, while we also documented a modest
      response in the draining genital and peripheral lymph nodes, the response at
      these sites also lagged behind peak virus production in these LT compartments.
      Third, we found that the response in GALT was surprisingly low or undetectable,
      possibly contributing to the severe and sustained depletion of CD4+ T lymphocytes
      in the GALT. Thus, the virus-specific CD8+ T-lymphocyte response is "too late and
      too little" to clear infection and prevent CD4+ T-lymphocyte loss. However, the
      robust response in female reproductive tissues may be an encouraging sign that
      vaccines that rapidly induce high-frequency CD8+ T-lymphocyte responses might be
      able to prevent acquisition of HIV-1 infection by the most common route of
      transmission.

PMID- 15994818
TI  - The marine algal virus PpV01 has an icosahedral capsid with T=219 quasisymmetry.
AB  - Phaeocystis pouchetii virus (PpV01) infects and lyses the haptophyte Phaeocystis
      pouchetii (Hariot) Lagerheim and was first isolated from Norwegian coastal
      waters. We have used electron cryomicroscopy and three-dimensional image
      reconstruction methods to examine the native morphology of PpV01 at a resolution
      of 3 nm. The icosahedral capsid of PpV01 has a maximum diameter of 220 nm and is
      composed of 2,192 capsomers arranged with T=219 quasisymmetry. One specific
      capsomer in each asymmetric unit contains a fiber-like protrusion. Density
      attributed to the presence of a lipid membrane appears just below (inside) the
      capsid. PpV01 is the largest icosahedral virus whose capsid structure has been
      determined in three dimensions from images of vitrified samples. Striking
      similarities in the structures of PpV01 and a number of other large double
      stranded DNA viruses are consistent with a growing body of evidence that they
      share a common evolutionary origin.

PMID- 15994819
TI  - Protease-dependent uncoating of a complex retrovirus.
AB  - Although retrovirus egress and budding have been partly unraveled, little is
      known about early stages of the replication cycle. In particular, retroviral
      uncoating, a process during which incoming retroviral cores are altered to allow
      the integration of the viral genome into host chromosomes, is poorly understood.
      To get insights into these early events of the retroviral cycle, we have used
      foamy complex retroviruses as a model. In this report, we show that a protease
      defective foamy retrovirus is noninfectious, although it is still able to bud and
      enter target cells efficiently. Similarly, a retrovirus mutated in an essential
      viral protease-dependent cleavage site in the central part of Gag is
      noninfectious. Following entry, wild-type and mutant retroviruses are able to
      traffic along microtubules towards the microtubule-organizing center (MTOC).
      However, whereas nuclear import of Gag and of the viral genome was observed for
      the wild-type virus as early as 8 hours postinfection, incoming capsids and
      genome from mutant viruses remained at the MTOC. Interestingly, a specific viral
      protease-dependent Gag cleavage product was detected only for the wild-type
      retrovirus early after infection, demonstrating that cleavage of Gag by the viral
      protease at this stage of the virus life cycle is absolutely required for
      productive infection, an unprecedented observation among retroviruses.

PMID- 15994820
TI  - A downstream polyadenylation element in human papillomavirus type 16 L2 encodes
      multiple GGG motifs and interacts with hnRNP H.
AB  - Production of human papillomavirus type 16 (HPV-16) virus particles is totally
      dependent on the differentiation-dependent induction of viral L1 and L2 late gene
      expression. The early polyadenylation signal in HPV-16 plays a major role in the
      switch from the early to the late, productive stage of the viral life cycle.
      Here, we show that the L2 coding region of HPV-16 contains RNA elements that are
      necessary for polyadenylation at the early polyadenylation signal. Consecutive
      mutations in six GGG motifs located 174 nucleotides downstream of the
      polyadenylation signal resulted in a gradual decrease in polyadenylation at the
      early polyadenylation signal. This caused read-through into the late region,
      followed by production of the late mRNAs encoding L1 and L2. Binding of hnRNP H
      to the various triple-G mutants correlated with functional activity of the HPV-16
      early polyadenylation signal. In addition, the polyadenylation factor CStF-64 was
      also found to interact specifically with the region in L2 located 174 nucleotides
      downstream of the early polyadenylation signal. Staining of cervix epithelium
      with anti-hnRNP H-specific antiserum revealed high expression levels of hnRNP H
      in the lower layers of cervical epithelium and a loss of hnRNP H production in
      the superficial layers, supporting a model in which a differentiation-dependent
      down regulation of hnRNP H causes a decrease in HPV-16 early polyadenylation and
      an induction of late gene expression.

PMID- 15994821
TI  - ERV3 and related sequences in humans: structure and RNA expression.
AB  - The ERV3 locus at chromosome 7q11 is a much studied human endogenous retroviral
      (HERV) sequence, owing to an env open reading frame (ORF) and placental RNA and
      protein expression. An analysis of the human genome demonstrated that ERV3 is one
      of a group of 41 highly related elements (ERV3-like HERVs) which use proline,
      isoleucine, or arginine tRNA in their primer binding sites. In addition to
      elements closely related to ERV3, the group included the previously known
      retinoic acid-inducible element, RRHERVI, also referred to as HERV15, but was
      separate from the related HERV-E elements. The ERV3-like elements are defective.
      The only element with an ORF among gag, pro, pol, and env genes was the env ORF
      of the original ERV3 locus. A search in dbEST revealed ERV3 RNA expression in
      placenta, skin, carcinoid tumor, and adrenal glands. Expression was also studied
      with newly developed real-time quantitative PCRs (QPCR) of ERV3 and HERV-E(4-1)
      env sequences. Results from a novel histone 3.3 RNA QPCR result served as the
      expression control. QPCR results for ERV3 were compatible with previously
      published results, with a stronger expression in adrenal gland and placenta than
      in 15 other human tissues. The expression of the envelope (env) of ERV3 at
      chromosome 7q11 was also studied by using stringent in situ hybridization.
      Expression was found in corpus luteum, testis, adrenal gland, Hassal's bodies in
      thymus, brown fat, pituitary gland, and epithelium of the lung. We conclude that
      ERV3 env is most strongly expressed in adrenal and sebaceous glands as well as in
      placenta.

PMID- 15994822
TI  - A genetically engineered attenuated coxsackievirus B3 strain protects mice
      against lethal infection.
AB  - Coxsackievirus B3 (CVB3) is a common human pathogen that is endemic throughout
      the world. There is currently no vaccine available, although the virus is known
      to be highly lethal to newborns and has been associated with heart disease and
      pancreatitis in older children and adults. Previously, we showed that the
      virulence of CVB3 is reduced by a lysine-to-arginine substitution in the capsid
      protein VP2 (K2168R) or a glutamic acid-to-glycine substitution in VP3 (E3060G).
      In this report, we show that the double mutant virus CVB3(KR/EG) displays
      additional attenuation, particularly for the pancreas, in A/J mice. In addition,
      two other attenuating mutations have been identified in the capsid protein VP1.
      When either the aspartic acid residue D1155 was replaced with glutamic acid or
      the proline residue P1126 was replaced with methionine, the resulting mutant also
      possessed an attenuated phenotype. Moreover, when either of these mutations was
      incorporated into CVB3(KR/EG), the resulting triple mutant viruses,
      CVB3(KR/EG/DE) and CVB3(KR/EG/PM), were completely noncardiovirulent and caused
      only small foci of damage to the pancreas, even at a high dose. Both triple
      mutants were found to be immunogenic, and a single injection of young A/J mice
      with either was found to protect them from a subsequent lethal challenge with
      wild-type CVB3. These findings indicate that the triple mutants could be
      exploited for the development of a live attenuated vaccine against CVB3.

PMID- 15994823
TI  - Growth suppression induced by downregulation of E6-AP expression in human
      papillomavirus-positive cancer cell lines depends on p53.
AB  - The ubiquitin-protein ligase E6-AP is utilized by the E6 oncoprotein of human
      papillomaviruses (HPVs) associated with cervical cancer to target the tumor
      suppressor p53 for degradation. Here, we report that downregulation of E6-AP
      expression by RNA interference results in both the accumulation of p53 and growth
      suppression of the HPV-positive cervical cancer cell lines HeLa and SiHa. In
      addition, HeLa cells, in which p53 expression was suppressed by RNA interference,
      are significantly less sensitive to the downregulation of E6-AP expression with
      respect to growth suppression than parental HeLa cells. These data indicate that
      the anti-growth-suppressive properties of E6-AP in HPV-positive cells depend on
      its ability to induce p53 degradation.

PMID- 15994824
TI  - Cloning and identification of a microRNA cluster within the latency-associated
      region of Kaposi's sarcoma-associated herpesvirus.
AB  - MicroRNAs (miRNAs) are small, noncoding regulatory RNA molecules that bind to 3'
      untranslated regions (UTRs) of mRNAs to either prevent their translation or
      induce their degradation. Previously identified in a variety of organisms ranging
      from plants to mammals, miRNAs are also now known to be produced by viruses. The
      human gammaherpesvirus Epstein-Barr virus has been shown to encode miRNAs, which
      potentially regulate both viral and cellular genes. To determine whether Kaposi's
      sarcoma-associated herpesvirus (KSHV) encodes miRNAs, we cloned small RNAs from
      KSHV-positive primary effusion lymphoma-derived cells and endothelial cells.
      Sequence analysis revealed 11 isolated RNAs of 19 to 23 bases in length that
      perfectly align with KSHV. Surprisingly, all candidate miRNAs mapped to a single
      genomic locale within the latency-associated region of KSHV. These data suggest
      that viral and host cellular gene expression may be regulated by miRNAs during
      both latent and lytic KSHV replication.

PMID- 15994825
TI  - Evidence of recombination between divergent hepatitis E viruses.
AB  - Phylogenetic and recombination analysis was performed on 32 complete hepatitis E
      virus (HEV) genomes from infected humans and pigs. For the first time, evidence
      for recombination between divergent HEV strains was obtained, with at least two
      strains being found to have discordant phylogenetic relationships consistent with
      the occurrence of intragenotype recombination. This finding confirms that humans
      can be dually infected with divergent HEV strains and has implications for the
      emergence and evolution of new HEV epidemics.

PMID- 15994826
TI  - Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition
      of Stat2 expression and alpha/beta interferon responsiveness.
AB  - Respiratory syncytial virus (RSV) subverts the antiviral interferon (IFN)
      response, but the mechanism for this evasion was unclear. Here we show that RSV
      preferentially inhibits IFN-alpha/beta signaling by expression of viral NS1 and
      NS2. Thus, RSV infection or expression of recombinant NS1 and NS2 in epithelial
      host cells causes a marked decrease in Stat2 levels and the consequent downstream
      IFN-alpha/beta response. Similarly, NS1/NS2-deficient RSV no longer decreases
      Stat2 levels or IFN responsiveness. RSV infection decreased human but not mouse
      Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host
      range, as well as immune subversion.

PMID- 15994827
TI  - Identification of TRAIL as an interferon regulatory factor 3 transcriptional
      target.
AB  - Interferon production and apoptosis in virus-infected cells are necessary to
      prevent progeny virus production and to eliminate infected cells. Paramyxovirus
      infection induces apoptosis through interferon regulatory factor 3 (IRF-3), but
      the exact mechanism of how IRF-3 functions is unknown. We show that IRF-3 is
      involved in the transcriptional induction of TRAIL, a key player in the apoptosis
      pathway. IRF-3 upregulates TRAIL transcription following viral infection and
      binds an interferon-stimulated response element in the TRAIL promoter. The mRNA
      for TRAIL and its receptor, DR5, are induced following viral infection. These
      studies identify TRAIL as a novel IRF-3 transcriptional target.

PMID- 15994828
TI  - Identification of proteins phosphorylated directly by the Us3 protein kinase
      encoded by herpes simplex virus 1.
AB  - We have developed a system to analyze the specific protein kinase activity of
      herpes simplex virus 1 Us3 in vitro and shown that Us3 directly phosphorylates
      viral proteins UL34, ICP22, and Us9 and the cellular protein Bad, previously
      reported to be putative substrates. Using this system, we determined the
      phosphorylation sites of UL34 and identified UL31 as a previously unreported,
      novel substrate of Us3. This system will be useful for further identification of
      Us3 substrates and their phosphorylation sites, clarification of the role of Us3
      in viral replication, and identification of additional Us3 function(s).

PMID- 15994829
TI  - Dissection of gammaretroviral receptor function by using type III phosphate
      transporters as models.
AB  - Gammaretroviruses that enter cells via binding to a surface receptor use one of
      two fundamental mechanisms. In the first, binding of the virus particle to its
      cognate receptor is followed by fusion and internalization. The second, less
      common mechanism requires the addition of an accessory protein in order to
      achieve fusion and entry into the target cells; this protein is usually the
      soluble form of the envelope protein containing the receptor-binding domain
      (RBD). For some viruses, such as amphotropic murine leukemia virus (A-MLV),
      particles with fusion-defective envelope proteins can enter cells in the presence
      of their own RBD or that of another viral envelope, regardless of its cognate
      receptor, suggesting that these viruses share a common entry mechanism. A notable
      exception is gibbon ape leukemia virus (GALV). Fusion-impaired GALV envelope
      mutants can be trans-activated for infectivity only by GALV RBDs. Using dually
      functional GALV/A-MLV receptors, we examined the role of receptor with respect to
      which RBD could overcome fusion impaired virus entry.

PMID- 15994830
TI  - Comparison of the genetic recombination rates of human immunodeficiency virus
      type 1 in macrophages and T cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) exhibits a high level of genetic
      variation generated by frequent mutation and genetic recombination during reverse
      transcription. We have measured HIV-1 recombination rates in T cells in one round
      of virus replication. It was recently proposed that HIV-1 recombines far more
      frequently in macrophages than in T cells. In an attempt to delineate the
      mechanisms that elevate recombination, we measured HIV-1 recombination rates in
      macrophages at three different marker distances. Surprisingly, the recombination
      rates were comparable in macrophages and in T cells. In addition, we observed
      similar recombination rates in two monocytic cell lines regardless of the
      differentiation status. These results indicate that HIV-1 undergoes similar
      numbers of recombination events when infecting macrophages and T cells.

PMID- 15994831
TI  - RNA-dependent protein kinase is required for alpha-1 interferon transgene-induced
      resistance to genital herpes simplex virus type 2.
AB  - We investigated the mechanism of resistance to genital herpes simplex virus type
      2 (HSV-2) infection in mice transfected with the murine alpha-1 interferon (IFN
      alpha1) transgene. In situ transfection of mice with the IFN-alpha1 transgene
      resulted in an elevation in an IFN-responsive gene, RNA-dependent protein kinase
      (PKR), but not 2',5'-oligoadenylate synthetases (OAS), in vaginal tissue. Coupled
      with the finding that mice lacking a functional PKR pathway were no longer
      resistant to genital HSV-2 infection following transfection with the IFN-alpha1
      transgene in comparison to wild-type mice or mice lacking a functional OAS
      pathway, these results suggest that PKR is the dominant antiviral pathway
      activated by the IFN-alpha1 transgene.

PMID- 15994832
TI  - Evidence for NF-kappaB- and CBP-independent repression of p53's transcriptional
      activity by human T-cell leukemia virus type 1 Tax in mouse embryo and primary
      human fibroblasts.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein can repress the
      transcriptional activity of the tumor suppressor protein p53. However, it remains
      controversial whether Tax requires NF-kappaB factors/activity and/or p300/CBP in
      order to inactivate p53 function. To address this issue, we have investigated
      Tax's effect on p53's transcriptional activation in IkappaB-kinase-deficient
      mouse embryonic fibroblasts (MEFs); some of which are entirely silent for Tax
      induced NF-kappaB activity. We found that, in IKKalpha-/-, IKKbeta-/-, and
      IKKgamma-/- MEFs, p53 activation of a prototypic responsive plasmid (pG13
      luciferase) was repressed by wild-type Tax. Curiously, p53's activity in MEFs was
      also repressed by a p300/CBP-binding deficient Tax protein. Our results highlight
      the complex nature of Tax-mediated repression of p53- activity, which requires
      further investigation.

PMID- 15994833
TI  - Role of CXCR3 in the immune response to murine gammaherpesvirus 68.
AB  - The chemokine IP-10 (CXCL10) and its cellular receptor CXCR3 are upregulated in
      the lung during murine gammaherpesvirus 68 (MHV-68) infection. In order to
      determine the role of the CXCR3 chemokine receptor in the immune response to MHV
      68, CXCR3-/- mice were infected with the virus. CXCR3-/- mice showed delayed
      clearance of replicating MHV-68 from the lungs. This correlated with delayed T
      cell recruitment to the lungs and reduced cytolytic activity prior to viral
      clearance. Splenomegaly and the numbers of latently infected cells per spleen
      were transiently increased. However, CXCR3-/- mice showed normal virus-specific
      antibody titers and effective long-term control of MHV-68 infection.

PMID- 15994834
TI  - Herpes simplex virus type 1 single-strand DNA binding protein ICP8 enhances the
      nuclease activity of the UL12 alkaline nuclease by increasing its processivity.
AB  - UL12 is a 5'- to 3'-exonuclease encoded by herpes simplex virus type 1 (HSV-1)
      which degrades single- and double-stranded DNA. UL12 and the single-strand DNA
      binding protein ICP8 mediate a strand exchange reaction. We found that ICP8
      inhibited UL12 digestion of single-stranded DNA but stimulated digestion of
      double-stranded DNA threefold. The stimulatory effect of ICP8 was independent of
      a strand exchange reaction; furthermore, the effect was specific to ICP8, as it
      could not be reproduced by Escherichia coli single-stranded DNA binding protein.
      The effect of ICP8 on the rate of UL12 double-stranded DNA digestion is
      attributable to an increase in processivity in the presence of ICP8.

PMID- 15994835
TI  - Reduced mobilization of Rev-responsive element-deficient lentiviral vectors.
AB  - Infection of cells transduced with a lentiviral vector by human immunodeficiency
      virus (HIV) could lead to packaging of the lentiviral vector RNA into HIV
      particles and unintended transfer of the vector. To prevent this, the Rev
      responsive element (RRE) of an HIV-1 vector was functionally replaced by a
      heterologous RNA element (MS2). Providing Rev fused to an MS2 binding protein
      allowed efficient vector production. Mobilization of the vector from infected
      target cells was below the level of detection and at least 10(3)- to 10(4)-fold
      lower than for the RRE-containing vector. Thus, RRE-deficient lentiviral vectors
      provide a novel approach to reduce the risk of vector mobilization.

PMID- 15994836
TI  - Intrapatient escape in the A*0201-restricted epitope SLYNTVATL drives evolution
      of human immunodeficiency virus type 1 at the population level.
AB  - The hypothesis that the intrapatient emergence of cytotoxic T-lymphocyte escape
      variants contributes to the evolution of human immunodeficiency virus type 1 at
      the population (interpatient) level was tested using the HLA-A*0201-restricted
      gag p17 epitope SLYNTVATL. Using a simple experimental design, we investigated
      the evolutionary processes operating within this epitope among patients while
      compensating for the confounding influence of intrapatient natural selection.
      Using this approach, we revealed a pattern of A*0201-driven escape within
      patients, followed by the sustained transmission of these escape variants among
      patients irrespective of their HLA type.

PMID- 15994837
TI  - Altered O-glycosylation and sulfation of airway mucins associated with cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is the most lethal genetic disorder in Caucasians and is
      characterized by the production of excessive amounts of viscous mucus secretions
      in the airways of patients, leading to airway obstruction, chronic bacterial
      infections, and respiratory failure. Previous studies indicate that CF-derived
      airway mucins are glycosylated and sulfated differently compared with mucins from
      nondiseased (ND) individuals. To address unresolved questions about mucin
      glycosylation and sulfation, we examined O-glycan structures in mucins purified
      from mucus secretions of two CF donors versus two ND donors. All mucins contained
      galactose (Gal), N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc),
      fucose (Fuc), and sialic acid (Neu5Ac). However, CF mucins had higher sugar
      content and more O-glycans compared with ND mucins. Both ND and CF mucins
      contained GlcNAc-6-sulfate (GlcNAc-6-Sul), Gal-6-Sul, and Gal-3-Sul, but CF
      mucins had higher amounts of the 6-sulfated species. O-glycans were released from
      CF and ND mucins and derivatized with 2-aminobenzamide (2-AB), separated by ion
      exchange chromatography, and quantified by fluorescence. There was nearly a two
      fold increase in sulfation and sialylation in CF compared with ND mucin. High
      performance liquid chromatography (HPLC) profiles of glycans showed differences
      between the two CF samples compared with the two ND samples. Glycan compositions
      were defined by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS). Unexpectedly, 260 compositional types of O-glycans
      were identified, and CF mucins contained a higher proportion of sialylated and
      sulfated O-glycans compared with ND mucins. These profound structural differences
      in mucin glycosylation in CF patients may contribute to inflammatory responses
      and increased pathogenesis by Pseudomonas aeruginosa.

PMID- 15994838
TI  - Child health in Africa: 2005 a year of hope?

PMID- 15994839
TI  - The relative importance of carbohydrate and nitrogen for the resprouting ability
      of Quercus crispula seedlings.
AB  - BACKGROUND AND AIMS: Plants need some kind of stored resources to resprout after
      shoot destruction. The aim of this study was to determine the relative importance
      of carbohydrate and nitrogen (N) storage levels for their ability to resprout.
      METHODS: A shoot clipping experiment was conducted on Quercus crispula seedlings,
      which were grown in a factorial experimental design, with two light levels (40%
      and 3% of full light) and three nutrient concentrations (low, medium and high).
      KEY RESULTS: At the time of shoot clipping (the end of spring leaf expansion),
      seedlings exposed to 40% light had an average total non-structural carbohydrate
      (TNC) concentration of 17.0% in their roots compared with 4.9% in the roots of
      seedlings exposed to 3% light, and the average amount of TNC (TNC pools) in the
      roots was 203.8 mg and 20.0 mg at 40% light and 3% light, respectively. In
      contrast, root N concentration averaged 2.3% in the 3% light treatment compared
      with 1.2% in the 40% light treatment, and it increased with successive rises in
      nutrient concentrations at both light levels. Regardless of the nutrient status,
      at the 40% light level >80% of the seedlings resprouted after shoot clipping. Few
      seedlings, however, resprouted at the 3% light level, particularly in the medium-
      and high-nutrient treatments. Furthermore, both root TNC concentrations and TNC
      pools decreased after resprouting, but the amount of root N remained constant.
      CONCLUSIONS: These results suggest that carbohydrate storage has a stronger
      influence on resprouting in Quercus crispula than N storage. However, the size of
      the resprouting shoot was positively correlated with the amount of both N and TNC
      in roots. The level of N storage is, therefore, also important for the growth of
      resprouting shoots.

PMID- 15994840
TI  - Molecular phylogeny, recent radiation and evolution of gross morphology of the
      rhubarb genus Rheum (Polygonaceae) inferred from chloroplast DNA trnL-F
      sequences.
AB  - BACKGROUND AND AIMS: Rheum, a highly diversified genus with about 60 species, is
      mainly confined to the mountainous and desert regions of the Qinghai-Tibetan
      plateau and adjacent areas. This genus represents a good example of the extensive
      diversification of the temperate genera in the Qinghai-Tibetan plateau, in which
      the forces to drive diversification remain unknown. To date, the infrageneric
      classification of Rheum has been mainly based on morphological characters.
      However, it may have been subject to convergent evolution under habitat pressure,
      and the systematic position of some sections are unclear, especially Sect.
      Globulosa, which has globular inflorescences, and Sect. Nobilia, which has semi
      translucent bracts. Recent palynological research has found substantial
      contradictions between exine patterns and the current classification of Rheum.
      Two specific objectives of this research were (1) to evaluate possible
      relationships of some ambiguous sections with a unique morphology, and (2) to
      examine possible occurrence of the radiative speciation with low genetic
      divergence across the total genus and the correlation between the extensive
      diversification time of Rheum and past geographical events, especially the recent
      large-scale uplifts of the Qinghai-Tibetan Plateau. METHODS: The chloroplast DNA
      trnL-F region of 29 individuals representing 26 species of Rheum, belonging to
      seven out of eight sections, was sequenced and compared. The phylogenetic
      relationships were further constructed based on the sequences obtained. KEY
      RESULTS: Despite the highly diversified morphology, the genetic variation in this
      DNA fragment is relatively low. The molecular phylogeny is highly inconsistent
      with gross morphology, pollen exine patterns and traditional classifications,
      except for identifying all samples of Sect. Palmata, three species of Sect.
      Spiciformia and a few species of Sect. Rheum as corresponding monophyletic
      groups. The monotypic Sect. Globulosa showed a tentative position within the
      clade comprising five species of Sect. Rheum. All of the analyses revealed the
      paraphyly of R. nobile and R. alexandrae, the only two species of Sect. Nobilia
      circumscribed by the possession of large bracts. The crude calibration of
      lineages based on trnL-F sequence differentiation implied an extensive
      diversification of Rheum within approx. 7 million years. CONCLUSIONS: Based on
      these results, it is suggested that the rich geological and ecological diversity
      caused by the recent large-scale uplifts of the Qinghai-Tibetan Plateau since the
      late Tertiary, coupled with the oscillating climate of the Quaternary stage,
      might have promoted rapid speciation in small and isolated populations, as well
      as allowing the fixation of unique or rare morphological characters in Rheum.
      Such a rapid radiation, combined with introgressive hybridization and reticulate
      evolution, may have caused the transfer of cpDNA haplotypes between
      morphologically dissimilar species, and might account for the inconsistency
      between morphological classification and molecular phylogeny reported here.

PMID- 15994841
TI  - Genetic variation in Echinacea angustifolia along a climatic gradient.
AB  - BACKGROUNDS AND AIMS: Echinacea angustifolia is a widespread species distributed
      throughout the Great Plains region of North America. Genetic differentiation
      among populations was investigated along a 1500 km north-south climatic gradient
      in North America, a region with no major geographical barriers. The objective of
      the study was to determine if genetic differentiation of populations could be
      explained by an isolation-by-distance model or by associations with climatic
      parameters known to affect plant growth and survival. METHODS: Historical
      climatic data were used to define the nature of the climatic gradient and AFLP
      markers were used to establish patterns of population genetic differentiation
      among ten Echinacea populations collected from North Dakota to Oklahoma. A total
      of 1290 fragments were scored using six EcoRI/MseI and three PstI/MseI primer
      combinations. Assessment of the correlation between climatic, genetic and
      geographic distances was assessed by Mantel and partial Mantel tests. KEY
      RESULTS: PstI/MseI combinations produced significantly fewer fragments, but a
      larger percentage was unique compared with EcoRI/MseI markers. Using estimates of
      F(ST), populations in Oklahoma and southern Kansas were identified as the most
      divergent from the other populations. Both the neighbour-joining tree and
      principal co-ordinate analysis clustered the populations in a north-south spatial
      orientation. About 60% of the genetic variation was found within populations, 20%
      among populations and the remaining 20% was partitioned among groups that were
      defined by the topology of the neighbour-joining tree. Significant support was
      found for the isolation-by-distance model independent of the effects of annual
      mean precipitation, but not from annual mean temperature and freeze-free days.
      CONCLUSIONS: Echinacea angustifolia populations exhibit genetic divergence along
      a north-south climatic gradient. The data support an isolation-by-distance
      restriction in gene flow that is independent of annual mean precipitation.

PMID- 15994842
TI  - Recurring challenges from a necrotrophic fungal plant pathogen: a case study with
      Leptosphaeria maculans (causal agent of blackleg disease in brassicas) in Western
      Australia.
AB  - BACKGROUND: Blackleg disease of Brassica napus, caused by the necrotrophic fungus
      Leptosphaeria maculans, causes severe yield losses in Australia, Europe and
      Canada. In Western Australia, it nearly destroyed the oilseed rape industry in
      1972 when host genotypes and conducive environmental conditions favoured severe
      epidemics. The introduction of cultivars with polygenic resistance and the
      adoption of sound cultural practices two decades later helped to manage the
      disease. These were abandoned by many farmers in recent years in favour of the
      effective but ephemeral resistance conferred by the single dominant gene-based
      resistance derived from B. rapa ssp. sylvestris. Recently, several cultivars
      carrying this gene have collapsed widely within a period of 3 years after their
      commercial release. An environment conducive to the disease and the association
      of the pathogen with susceptible hosts in Western Australia for over 80 years
      together have led to the proliferation of L. maculans races, amounting to half of
      all races delineated to date from Europe, including the United Kingdom, Canada
      and Australia. SCOPE: This review demonstrates the problems that emerge when
      traditional cultural practices employed, along with cultivars containing
      polygenic resistance to a serious necrotrophic pathogen, are discarded in
      preference to the exclusive deployment of effective but ephemeral single dominant
      gene-based resistance to the disease across Southern Australia. CONCLUSIONS:
      Single dominant gene-based resistance currently available, on its own, will not
      confer durable resistance to blackleg disease in oilseed rape. Return to earlier
      management practices, including reliance upon polygenic resistance and induced
      resistance, may be the best currently available options to maintain production in
      regions across Southern Australia predisposed to severe epidemics.

PMID- 15994843
TI  - The role of exo-(1-->4)-beta-galactanase in the mobilization of polysaccharides
      from the cotyledon cell walls of Lupinus angustifolius following germination.
AB  - BACKGROUND AND AIMS: The cotyledons of Lupinus angustifolius contain large
      amounts of cell wall storage polysaccharide (CWSP) composed mainly of (1-->4)
      beta-linked D-galactose residues in the form of branches attached to a
      rhamnogalacturonan core molecule. An exo-(1-->4)-beta-galactanase with a very
      high specificity towards (1-->4)-beta-linked D-galactan has been isolated from L.
      angustifolius cotyledons, and shown to vary (activity and specific protein) in
      step with CWSP mobilization. This work aimed to confirm the hypothesis that
      galactan is the main polymer retrieved from the wall during mobilization at the
      ultrastructural level, using the purified exo-galactanase as a probe. METHODS:
      Storage mesophyll cell walls ('ghosts') were isolated from the cotyledons of
      imbibed but ungerminated lupin seeds, and also from cotyledons of seedlings after
      the mobilization of the CWSP. The pure exo-(1-->4)-beta-galactanase was coupled
      to colloidal gold particles and shown to be a specific probe for (1-->4)-beta-D
      galactan. They were used to localize galactan in ultrathin sections of L.
      angustifolius cotyledonary mesophyll tissue during CWSP mobilization. KEY
      RESULTS: On comparing the morphologies of isolated cell walls, the post
      mobilization 'ghosts' did not have the massive wall-thickenings of pre
      mobilization walls. Compositional analysis showed that the post-mobilization
      walls were depleted in galactose and, to a lesser extent, in arabinose. When pre
      mobilization ghosts were treated with the pure exo-galactanase, they became
      morphologically similar to the post-mobilization ghosts. They were depleted of
      approximately 70% of the galactose residues that would have been mobilized in
      vivo, and retained all the other sugar residues originally present. Sharply
      defined electron-transparent wall zones or pockets are associated with CWSP
      mobilization, being totally free of galactan, whereas wall areas immediately
      adjacent to them were apparently undepleted. CONCLUSIONS: The exo-(1-->4)-beta
      galactanase is the principal enzyme involved in CWSP mobilization in lupin
      cotyledons in vivo. The storage walls dramatically change their texture during
      mobilization as most of the galactan is hydrolysed during seedling development.

PMID- 15994844
TI  - Molecular systematics and biogeography of Crawfurdia, Metagentiana and
      Tripterospermum (Gentianaceae) based on nuclear ribosomal and plastid DNA
      sequences.
AB  - BACKGROUND AND AIMS: The systematic position of the genus Metagentiana and its
      phylogenetic relationships with Crawfurdia, Gentiana and Tripterospermum have not
      been explicitly addressed. These four genera belong to one of two subtribes
      (Gentianinae) of Gentianeae. The aim of this paper is to examine the systematic
      position of Crawfurdia, Metagentiana and Tripterospermum and to clarify their
      phylogenetic affinities more clearly using ITS and trnL intron sequences.
      METHODS: Nucleotide sequences from the internal transcribed spacers (ITS) of
      nuclear ribosomal DNA and the plastid DNA trnL (UAA) intron were analysed
      phylogenetically. Ten of fourteen Metagentiana species were sampled, together
      with 40 species of other genera in the subtribe Gentianinae. KEY RESULTS: The
      data support several previously published conclusions relating to the separation
      of Metagentiana from Gentiana and its closer relationships to Crawfurdia and
      Tripterospermum based on studies of gross morphology, floral anatomy,
      chromosomes, palynology, embryology and previous molecular data. The molecular
      clock hypothesis for the tested sequences in subtribe Gentianinae was not
      supported by the data (P < 0.05), so the clock-independent non-parametric rate
      smoothing method was used to estimate divergence time. This indicates that the
      separation of Crawfurdia, Metagentiana and Tripterospermum from Gentiana occurred
      about 11.4-21.4 Mya (million years ago), and the current species of these three
      genera diverged at times ranging from 0.4 to 6.2 Mya. CONCLUSIONS: The molecular
      analyses revealed that Crawfurdia, Metagentiana and Tripterospermum do not merit
      status as three separate genera, because sampled species of Crawfurdia and
      Tripterospermum are embedded within Metagentiana. The speciation and rapid
      radiation of these three genera is likely to have occurred in western China as a
      result of upthrust of the Himalayas during the late Miocene and the Pleistocene.

PMID- 15994845
TI  - Health on the Internet: implications for health promotion.
AB  - The aim of this article is to discuss the implications of health on the Internet
      for health promotion, focusing in particular on the concept of empowerment.
      Empowering aspects of health on the Internet include the enabling of advanced
      information and knowledge retrieval, anonymity and convenience in accessing
      information, creation of social contacts and support independent of time and
      space, and challenging the expert-lay actor relationship. The disempowering
      aspects of health on the Internet are that it involves a shift towards the expert
      control and evaluation of sources of health information, that it widens the gap
      between 'information-rich' and 'information-poor' users, thus reproducing
      existing social divisions, and that the increase in medicalization and healthism
      results in increased anxiety and poorer health. The health promotive and
      empowering strategies presented in this article are directed at strengthening
      people's ability to evaluate different information sources in relation to their
      own interests and needs rather than in relation to scientific and/or professional
      standards.

PMID- 15994846
TI  - Genetics of polycystic ovary syndrome: searching for the way out of the
      labyrinth.
AB  - Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder
      presenting a challenge for clinical investigators. It is the most common
      endocrine disorder of women in reproductive age, a multifaceted reproductive,
      cosmetic and metabolic problem, with an enigmatic pathophysiological and
      molecular basis. Although the familial segregation has been noticed very early in
      the description of the syndrome and family studies in first-degree relatives of
      women diagnosed with PCOS reveal clustering of the disease, the genetic studies
      have not as yet determine the pattern of heredity. Part of the problem in genetic
      studies has been the lack of uniform criteria for diagnosis, heterogeneity of
      phenotypic features and the fact that the disorder is only expressed clinically
      in women during their reproductive years. Even within affected families and
      between sisters with polycystic ovaries, there is heterogeneity in presentation.
      However, regardless of diagnostic criteria used to identify profanes and to
      determine affected status in the kindred, the foundation of genetic studies
      suggests a strong familial component. Currently, PCOS is considered a polygenic
      trait that might result from the interaction of susceptible and protective
      genomic variants under the influence of environmental factors, whose role is
      under intensive investigation. Candidate genes cover a broad spectrum of an
      endless list of molecules which participate on every step of reproductive and
      metabolic pathways of this syndrome. Focused research in identification of these
      genes may provide valuable information and shed some light on the way out of the
      genomic labyrinth, elucidating the underlying pathophysiology and aiming at a
      more efficient therapeutic approach of this complicated endocrine disorder.

PMID- 15994847
TI  - Assisted reproduction: the epigenetic perspective.
AB  - Developmental pathways in humans and other organisms are buffered against changes
      in genotype and environment. Therefore, it should not come as a surprise that
      most of the children conceived by assisted reproduction technology (ART) are
      healthy, although ART bypasses a lot of biological filters and subjects the
      gametes and the early embryo to environmental stress. If, however, the buffer
      breaks down, the development of certain tissues or organs may follow abnormal
      trajectories. We argue that both normal and abnormal development in children
      conceived by ART can be explained by epigenetic mechanisms, which control the
      establishment and maintenance of gene expression patterns in the placenta and
      fetus. Imprinted genes are of special importance in this respect. There is
      increasing evidence that genetic factors in infertile couples as well as
      environmental factors (hormones and culture media) can have adverse effects on
      epigenetic processes controlling implantation, placentation, organ formation and
      fetal growth. In addition, loss of epigenetic control may expose hidden genetic
      variation.

PMID- 15994848
TI  - Halothane and sevoflurane inhibit Na/Ca exchange current in rat ventricular
      myocytes.
AB  - BACKGROUND: The electrogenic Na+/Ca2+ exchanger (NCX) represents the main
      extrusion pathway for Ca2+ in ventricular muscle and therefore plays an important
      role in the regulation of cytosolic Ca2+ and contraction. Halothane and
      sevoflurane modulate cytosolic Ca2+ regulation and at steady state are negatively
      inotropic, however, the involvement of anaesthetic-induced changes in NCX
      activity in these effects requires further study. METHODS: Ventricular myocytes
      were isolated using a standard collagenase/protease dispersion technique and
      superfused with a physiological salt solution at 30 degrees C. Whole-cell patch
      clamp technique was used to control membrane voltage. I(NCX) (identified as Ni2+
      sensitive current) was recorded using a ramp clamp protocol under conditions to
      inhibit contaminating currents. RESULTS: With 0.6 mM sevoflurane, outward I(NCX)
      at positive voltages (> or = 0 mV) and inward I(NCX) at voltages negative to -60
      mV was significantly reduced (P<0.05, n=13; I(NCX) reduced by 48% at +50 and 65%
      of control at -120 mV). Halothane (0.6 mM) inhibited outward I(NCX) at voltages
      positive to -10 mV and inward I(NCX) at voltages negative to -80 mV (P<0.05,
      n=10; I(NCX) reduced by 64% at +50 and 65% of control at -120 mV). Anaesthetic
      induced inhibition of both inward and outward current was not voltage-dependent.
      CONCLUSIONS: Inhibition of Ca2+ efflux via NCX (i.e. inward I(NCX)) during an
      exposure to halothane or sevoflurane would be expected to limit the negative
      inotropic effects of these agents and help maintain SR Ca2+ content.

PMID- 15994849
TI  - Characteristics of propofol-evoked vascular pain in anaesthetized rats.
AB  - BACKGROUND: In this study we have assessed vascular pain caused by the i.v.
      anaesthetic agent, propofol, using the flexor reflex response and compared this
      with that of capsaicin in anaesthetized intact rats. METHODS: Experiments were
      performed on 133 male Sprague-Dawley rats weighing 280-340 g. The animals were
      anaesthetized with urethane (1.3 g kg(-1), i.p.), and an arterial cannula was
      inserted to the level of the bifurcation of the femoral artery. The magnitude of
      the flexor reflex was examined by recording the electromyogram from the posterior
      biceps femoris/semitendinosus muscles. RESULTS: Our data show that the flexor
      reflexes evoked by intra-arterial (i.a.) injection of propofol (1%, 25-100
      microl) and capsaicin (0.05-0.2 microg) were dose dependent. An initial i.a.
      injection of procaine (2%, 200 microl) blocked both responses. Furthermore, the
      flexor reflex induced by these chemical stimuli were inhibited by morphine (5 mg
      kg(-1), s.c.) and restored with naloxone (1.5 mg kg(-1), s.c.). Pre-treatment
      with capsazepine (20 microg, i.a.), a selective VR1 antagonist, inhibited the
      capsaicin-evoked response, but not that of propofol. Indomethacin (10 mg kg(-1),
      i.p.), a non-selective cyclo-oxygenase inhibitor, inhibited only the propofol
      evoked response and this recovered with arterial PGE2 (5 microg). CONCLUSIONS:
      Collectively our data suggest that propofol-evoked vascular pain is mainly
      initiated by prostanoids.

PMID- 15994850
TI  - Isoflurane exerts antinociceptive and hypnotic properties at all ages in Fischer
      rats.
AB  - BACKGROUND: Some anaesthetic agents exhibit an age-dependent analgesic effect,
      for example nitrous oxide, which is ineffective in newborn rats. We investigated
      whether a similar time dependency existed for the responses to the volatile
      anaesthetic isoflurane. METHODS: The analgesic and hypnotic properties of
      isoflurane at various ages was assessed using four cohorts of Fischer rats aged
      approximately 7, 16, and 28 days and adults (11-12 weeks old). Intraplantar
      administration of formalin mimicked inflammatory pain, and its effects were
      assessed using immunohistochemical (c-Fos staining) and behavioural paradigms.
      The hypnotic properties of isoflurane were assessed using loss of righting
      reflex. RESULTS: Formalin administration produced a typical nociceptive response
      observed both behaviourally and immunohistochemically in all age groups; these
      nociceptive responses were significantly attenuated by isoflurane 0.5% at each
      age (P<0.05). Interestingly 7-day-old animals showed a significantly more potent
      hypnotic response than older animals (P<0.01): with adult rats being most
      resistant to isoflurane induced hypnosis (P<0.05). CONCLUSION: In contrast to
      nitrous oxide, isoflurane is an effective antinociceptive agent in neonatal rats.
      If the data can be extrapolated to clinical scenarios these results suggest that
      isoflurane may be analgesic in newborns as well as adult humans. In addition,
      isoflurane is a potent hypnotic, especially in the very young, which is in
      contrast to the neonate's relative resistance to anaesthesia as assessed by
      minimum alveolar concentration.

PMID- 15994851
TI  - Regulation of capillary hydraulic conductivity in response to an acute change in
      shear.
AB  - The effects of mechanical perturbations (shear stress, pressure) on microvascular
      permeability primarily have been examined in micropipette-cannulated vessels or
      in endothelial monolayers in vitro. The objective of this study is to determine
      whether acute changes in blood flow shear stress might influence measurements of
      hydraulic conductivity (L(p)) in autoperfused microvessels in vivo. Rat
      mesenteric microvessels were observed via intravital microscopy. Occlusion of a
      third-order arteriole with a micropipette was used to divert and increase flow
      through a nonoccluded capillary or fourth-order arteriolar branch. Transvascular
      fluid filtration rate in the branching vessel was measured with a Landis
      technique. Flow (shear)-induced increases in L(p) disappeared within 20-30 s of
      the removal of the shear and could be eliminated with nitric oxide synthase
      inhibition. The shear-induced increase in L(p) was greater in capillaries
      compared with terminal arterioles. An acute change in shear may regulate L(p) by
      a nitric oxide-dependent mechanism that displays heterogeneity within a
      microvascular network.

PMID- 15994853
TI  - Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating
      the forward mode of Na+/Ca2+ exchanger in mouse aorta.
AB  - The effect of Na+-K+ pump activation on endothelium-dependent relaxation (EDR)
      and on intracellular Ca2+ concentration ([Ca2+]i) was examined in mouse aorta and
      mouse aortic endothelial cells (MAECs). The Na+-K+ pump was activated by
      increasing extracellular K+ concentration ([K+]o) from 6 to 12 mM. In aortic
      rings, the Na+ ionophore monensin evoked EDR, and this EDR was inhibited by the
      Na+/Ca2+ exchanger (NCX; reverse mode) inhibitor KB-R7943. Monensin-induced Na+
      loading or extracellular Na+ depletion (Na+ replaced by Li+) increased [Ca2+]i in
      MAECs, and this increase was inhibited by KB-R7943. Na+-K+ pump activation
      inhibited EDR and [Ca2+]i increase (K+-induced inhibition of EDR and [Ca2+]i
      increase). The Na+-K+ pump inhibitor ouabain inhibited K+-induced inhibition of
      EDR. Monensin (>0.1 microM) and the NCX (forward and reverse mode) inhibitors
      2'4'-dichlorobenzamil (>10 microM) or Ni2+ (>100 microM) inhibited K+-induced
      inhibition of EDR and [Ca2+]i increase. KB-R7943 did not inhibit K+-induced
      inhibition at up to 10 microM but did at 30 microM. In current-clamped MAECs, an
      increase in [K+]o from 6 to 12 mM depolarized the membrane potential, which was
      inhibited by ouabain, Ni2+, or KB-R7943. In aortic rings, the concentration of
      cGMP was significantly increased by acetylcholine and decreased on increasing
      [K+]o from 6 to 12 mM. This decrease in cGMP was significantly inhibited by
      pretreating with ouabain (100 microM), Ni2+ (300 microM), or KB-R7943 (30
      microM). These results suggest that activation of the forward mode of NCX after
      Na+-K+ pump activation inhibits Ca2+ mobilization in endothelial cells, thereby
      modulating vasomotor tone.

PMID- 15994852
TI  - Naloxone does not influence cardiovascular responses to mild mental stress in
      postmenopausal women.
AB  - The interaction between central opioid activity, sex hormones, and the
      cardiovascular reactivity to stress is unknown. Twenty-eight healthy
      postmenopausal women, 16 without, and 12 with hormone replacement therapy (HRT)
      participated in this randomized, double-blind, cross-over study. The opioid
      receptor antagonist naloxone or placebo was administered intravenously on 2
      different days and mild mental stress was induced by the Stroop Color-Word Test.
      Cardiovascular responses were assessed noninvasively by impedance cardiography.
      Stress significantly increased stroke volume, cardiac output, blood pressure, and
      heart rate, which was not influenced by opioid receptor blockade. Whereas
      naloxone increased cortisol plasma concentrations irrespective of HRT status,
      luteinizing hormone concentrations, which were higher in non-HRT compared with
      HRT women, were increased by naloxone in women with HRT only. These data suggest
      that the opioidergic tone of the hypothalamus-pituitary-adrenal axis persists in
      postmenopausal women, irrespective of HRT use, while the opioidergic tone on the
      hypothalamus-pituitary-gonadal axis seems to depend on an estrogenic milieu.
      Naloxone does not alter cardiovascular mental stress reactions in postmenopausal
      women independent of their hormone substitution status.

PMID- 15994854
TI  - Increase in tension-dependent ATP consumption induced by cardiac troponin T
      mutation.
AB  - How different mutations in cardiac troponin T (cTnT) lead to distinct secondary
      downstream cellular remodeling in familial hypertrophic cardiomyopathy (FHC)
      remains elusive. To explore the molecular basis for the distinct impact of
      different mutations in cTnT on cardiac myocytes, we studied mechanical activity
      of detergent-skinned muscle fiber bundles from different lines of transgenic (TG)
      mouse hearts that express wild-type cTnT (WTTG), R92W cTnT, R92L cTnT, and Delta
      160 cTnT (deletion of amino acid 160). The amount of mutant cTnT is approximately
      50% of the total myocellular cTnT in both R92W and R92L TG mouse hearts and
      approximately 35% in Delta-160 TG mouse hearts. Myofilament Ca2+ sensitivity was
      enhanced in all mutant cTnT TG cardiac muscle fibers. Compared with the WTTG
      fibers, Ca2+ sensitivity increased significantly at short sarcomere length (SL)
      of 1.9 microm (P < 0.001) in R92W TG fibers by 2.2-fold, in R92L by 2.0-fold, and
      in Delta-160 by 1.3-fold. At long SL of 2.3 microm, Ca2+ sensitivity increased
      significantly (P < 0.01) in a similar manner (R92W, 2.5-fold; R92L, 1.9-fold;
      Delta-160, 1.3-fold). Ca2+-activated maximal tension remained unaltered in all TG
      muscle fibers. However, tension-dependent ATP consumption increased significantly
      in Delta-160 TG muscle fibers at both short SL (23%, P < 0.005) and long SL (37%,
      P < 0.0001), suggesting a mutation-induced change in cross-bridge detachment rate
      constant. Chronic stresses on relative cellular ATP level in cardiac myocytes may
      cause a strain on energy-dependent Ca2+ homeostatic mechanisms. This may result
      in pathological remodeling that we observed in Delta-160 TG cardiac myocytes
      where the ratio of sarco(endo)plasmic reticulum Ca2+-ATPase 2/phospholamban
      decreased significantly. Our results suggest that different types of stresses
      imposed on cardiac myocytes would trigger distinct cellular signaling, which
      leads to remodeling that may be unique to some mutants.

PMID- 15994855
TI  - Low-intensity exercise training delays onset of decompensated heart failure in
      spontaneously hypertensive heart failure rats.
AB  - Data regarding the effectiveness of chronic exercise training in improving
      survival in patients with congestive heart failure (CHF) are inconclusive.
      Therefore, we conducted a study to determine the effect of exercise training on
      survival in a well-defined animal model of heart failure (HF), using the lean
      male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically
      present with decompensated, dilated HF between approximately 18 and 23 mo of age.
      SHHF rats were assigned to sedentary or exercise-trained groups at 9 and 16 mo of
      age. Exercise training consisted of 6 mo of low-intensity treadmill running.
      Exercise training delayed the onset of overt HF and improved survival (P < 0.01),
      independent of any effects on the hypertensive status of the rats. Training
      delayed the myosin heavy chain (MyHC) isoform shift from alpha- to beta-MyHC that
      was seen in sedentary animals that developed HF. Exercise was associated with a
      concurrent increase in cardiomyocyte length (approximately 6%), width, and area
      and prevented the increase in the length-to-width ratio seen in sedentary animals
      in HF. The increases in proteinuria, plasma atrial natriuretic peptide, and serum
      leptin levels observed in rats with HF were suppressed by low-intensity exercise
      training. No significant alterations in sarco(endo)plasmic reticulum Ca2+ ATPase,
      phospholamban, or Na+/Ca2+ exchanger protein expression were found in response to
      training. Our results indicate that 6 mo of low-intensity exercise training
      delays the onset of decompensated HF and improves survival in the male SHHF rat.
      Similarly, exercise intervention prevented or suppressed alterations in several
      key variables that normally occur with the development of overt CHF. These data
      support the idea that exercise may be a useful and inexpensive intervention in
      the treatment of HF.

PMID- 15994857
TI  - Activation of estrogen receptor-alpha protects the in vivo rabbit heart from
      ischemia-reperfusion injury.
AB  - The estrogen receptor (ER) mediates estrogenic activity in a variety of organs,
      including those in the reproductive, cardiovascular, immune, and central nervous
      systems. Experimental studies have demonstrated that 17beta-estradiol (E2)
      protects the heart from ischemia-reperfusion injury. Two estrogen receptors, ER
      alpha and ER beta, mediate the actions of estrogen; however, it is not certain
      which ER mediates the cardioprotective effects of E2. In the present study, the
      ER-selective agonists 4,4',4''-[4-propyl-(1H)-pyrazole-1,3,5-triyl]tris-phenol
      (PPT; ER alpha) and 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ER beta) were
      assessed for their cardioprotective potential in an in vivo rabbit model of
      ischemia-reperfusion injury. Anesthetized female rabbits were administered PPT (3
      mg/kg), DPN (3 mg/kg), E2 (20 microg/rabbit), or vehicle intravenously 30 min
      before a 30-min occlusion of the left anterior descending coronary artery
      followed by 4 h of reperfusion. Acute treatment with E2 (17.7 +/- 2.9%; P <
      0.001) and PPT (18.1 +/- 2.9%; P < 0.001), but not DPN (45.3 +/- 2.4%)
      significantly decreased infarct size as a percent of area at risk compared with
      vehicle (45.3 +/- 2.4%). Coadministration of PPT or E2 with the ER antagonist ICI
      182,780 limited the infarct size-sparing effect of the compounds (43.8 +/- 6.6%
      and 40.6 +/- 5.7% respectively, expressed as a percentage of risk region). PPT
      reduced the release of cardiac-specific troponin-I and reduced the tissue
      deposition of the membrane attack complex and C-reactive protein similar to that
      of E2. The results indicate that activation of ER alpha, but not ER beta, is
      required for the observed cardioprotective effects of E2.

PMID- 15994856
TI  - Activation of PKC modulates blood-brain barrier endothelial cell permeability
      changes induced by hypoxia and posthypoxic reoxygenation.
AB  - The blood-brain barrier (BBB) is a metabolic and physiological barrier important
      for maintaining brain homeostasis. The aim of this study was to determine the
      role of PKC activation in BBB paracellular permeability changes induced by
      hypoxia and posthypoxic reoxygenation using in vitro and in vivo BBB models. In
      rat brain microvessel endothelial cells (RMECs) exposed to hypoxia (1% O2-99% N2;
      24 h), a significant increase in total PKC activity was observed, and this was
      reduced by posthypoxic reoxygenation (95% room air-5% CO2) for 2 h. The
      expression of PKC-betaII, PKC-gamma, PKC-eta, PKC-mu, and PKC-lambda also
      increased following hypoxia (1% O2-99% N2; 24 h), and these protein levels
      remained elevated following posthypoxic reoxygenation (95% room air-5% CO2; 2 h).
      Increases in the expression of PKC-epsilon and PKC-zeta were also observed
      following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Moreover,
      inhibition of PKC with chelerythrine chloride (10 microM) attenuated the hypoxia
      induced increases in [14C]sucrose permeability. Similar to what was observed in
      RMECs, total PKC activity was also stimulated in cerebral microvessels isolated
      from rats exposed to hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation
      (room air; 10 min). In contrast, hypoxia (6% O2-94% N2; 1 h) and posthypoxic
      reoxygenation (room air; 10 min) significantly increased the expression levels of
      only PKC-gamma and PKC-theta in the in vivo hypoxia model. These data demonstrate
      that hypoxia-induced BBB paracellular permeability changes occur via a PKC
      dependent mechanism, possibly by differentially regulating the protein expression
      of the 11 PKC isozymes.

PMID- 15994858
TI  - ET(A) receptor blockade prevents renal dysfunction in salt-sensitive hypertension
      induced by sensory denervation.
AB  - To test the hypothesis that activation of the endothelin type A (ET(A)) receptor
      contributes to decreased renal excretory function and increased blood pressure in
      sensory nerve-degenerated rats fed a high-salt diet, neonatal Wistar rats were
      given vehicle or capsaicin (CAP, 50 mg/kg s.c.) on the first and second day of
      life. After being weaned, vehicle or CAP-treated rats were fed a normal (NS,
      0.5%) or a high- (HS, 4%) sodium diet for 2 wk with or without ABT-627 (5 mg x
      kg(-1) x day(-1), a selective ET(A) receptor antagonist). Systolic blood pressure
      increased in CAP-treated rats fed a HS diet (CAP-HS) compared with vehicle
      treated rats fed a HS diet (CON-HS, 145 +/- 7 vs. 89 +/- 5 mmHg, P < 0.05).
      Creatinine clearance and fractional sodium excretion (FE(Na)) decreased in CAP-HS
      rats compared with CON-HS rats (creatinine clearance, 0.54 +/- 0.05 vs. 0.81 +/-
      0.09 ml x min(-1) x 100 g body wt(-1); FE(Na), 8.68 +/- 0.99 vs. 12.53 +/- 1.47%,
      respectively; P < 0.05). Water and sodium balance increased in CAP-HS rats
      compared with CON-HS (water balance, 20.2 +/- 1.5 vs. 15.5 +/- 1.9 ml/day; sodium
      balance, 11.9 +/- 3.1 vs. 2.4 +/- 0.3 meq/day, respectively; P < 0.05). The
      endothelin (ET)-1 levels in plasma and isolated glomeruli increased by about
      twofold in CAP-HS rats compared with CON-HS rats (P < 0.05). ABT-627 prevented
      the decrease in creatinine clearance and FE(Na), the increase in water and sodium
      balance, and the increase in blood pressure in CAP-HS rats (P < 0.05). Therefore,
      the blockade of the ET(A) receptor ameliorates the impairment of renal excretory
      function and prevents the elevation in blood pressure in salt-sensitive
      hypertension induced by degeneration of sensory nerves, indicating that the
      activation of the ET(A) receptor impairs renal function and contributes to the
      development of a salt-induced increase in blood pressure in this model.

PMID- 15994859
TI  - Clusterin: a protective mediator for ischemic cardiomyocytes?
AB  - We examined the relationship between clusterin and activated complement in human
      heart infarction and evaluated the effect of this protein on ischemic rat
      neonatal cardiomyoblasts (H9c2) and isolated adult ventricular rat cardiomyocytes
      as in vitro models of acute myocardial infarction. Clusterin protects cells by
      inhibiting complement and colocalizes with complement on jeopardized human
      cardiomyocytes after infarction. The distribution of clusterin and complement
      factor C3d was evaluated in the infarcted human heart. We also analyzed the
      protein expression of clusterin in ischemic H9c2 cells. The binding of endogenous
      and purified human clusterin on H9c2 cells was analyzed by flow cytometry.
      Furthermore, the effect of clusterin on the viability of ischemically challenged
      H9c2 cells and isolated adult ventricular rat cardiomyocytes was analyzed. In
      human myocardial infarcts, clusterin was found on scattered, morphologically
      viable cardiomyocytes within the infarcted area that were negative for
      complement. In H9c2 cells, clusterin was rapidly expressed after ischemia. Its
      expression was reduced after reperfusion. Clusterin bound to single annexin V
      positive or annexin V and propidium iodide-positive H9c2 cells. Clusterin
      inhibited ischemia-induced death in H9c2 cells as well as in isolated adult
      ventricular rat cardiomyocytes in the absence of complement. We conclude that
      ischemia induces the upregulation of clusterin in ischemically challenged, but
      viable, cardiomyocytes. Our data suggest that clusterin protects cardiomyocytes
      against ischemic cell death via a complement-independent pathway.

PMID- 15994860
TI  - Proteasome degradation of GRK2 during ischemia and ventricular tachyarrhythmias
      in a canine model of myocardial infarction.
AB  - Arrhythmia-prone subepicardial border zone (EBZ) tissue demonstrates decreased G
      protein receptor kinase 2 (GRK2) activity and increased sensitivity to
      isoproterenol 6-24 h after coronary artery ligation (CAL) in the dog. With the
      use of a semiquantitative immunofluorescence technique, the relative fluorescence
      intensity (RF) of GRK2 in EBZ decreased to 24% of that in a remote site (RS) (P <
      0.01, n = 30 cells from 3 dogs), whereas GRK5 RF did not change. Confocal studies
      of cardiac tissue from transgenic mice overexpressing GRK2 validated the use of a
      semilogarithmic relationship between RF and GRK2 activity. As shown with the use
      of quantitative real-time RT-PCR, both GRK2 and GRK5 mRNA were not decreased at
      24 h in EBZ (n = 6 dogs) relative to RS control, indicating that the decrease of
      GRK2 in the EBZ is likely due to posttranscriptional degradation following CAL.
      Pretreatment of six dogs with the selective proteasome inhibitor bortezomib
      provided 100% (EBZ) and 50% (infarct) protection against loss of GRK2 at 24 h.
      There was an absence of rapid (>300 beats/min) and very rapid (>360 beats/min)
      ventricular triplets that are highly predictive of sudden cardiac death during
      ECG monitoring in the bortezomib-pretreated animals in contrast to nonpretreated
      infarcted animals. We have demonstrated that the dramatic decrease in GRK2 in
      cardiac ischemic tissue can be largely blocked by prior proteasome blockade and
      that this is associated with significant cardioprotection against malignant
      ventricular tachyarrhythmias.

PMID- 15994861
TI  - Two high throughput technologies to detect segmental aneuploidies identify new
      Williams-Beuren syndrome patients with atypical deletions.
AB  - OBJECTIVE: To develop and compare two new technologies for diagnosing a
      contiguous gene syndrome, the Williams-Beuren syndrome (WBS). METHODS: The first
      proposed method, named paralogous sequence quantification (PSQ), is based on the
      use of paralogous sequences located on different chromosomes and quantification
      of specific mismatches present at these loci using pyrosequencing technology. The
      second exploits quantitative real time polymerase chain reaction (QPCR) to assess
      the relative quantity of an analysed locus. RESULTS: A correct and unambiguous
      diagnosis was obtained for 100% of the analysed samples with either technique (n
      = 165 and n = 155, respectively). These methods allowed the identification of two
      patients with atypical deletions in a cohort of 182 WBS patients. Both patients
      presented with mild facial anomalies, mild mental retardation with impaired
      visuospatial cognition, supravalvar aortic stenosis, and normal growth indices.
      These observations are consistent with the involvement of GTF2IRD1 or GTF2I in
      some of the WBS facial features. CONCLUSIONS: Both PSQ and QPCR are robust, easy
      to interpret, and simple to set up. They represent a competitive alternative for
      the diagnosis of segmental aneuploidies in clinical laboratories. They have
      advantages over fluorescence in situ hybridisation or microsatellites/SNP
      genotyping for detecting short segmental aneuploidies as the former is costly and
      labour intensive while the latter depends on the informativeness of the
      polymorphisms.

PMID- 15994862
TI  - Mutation screening in Borjeson-Forssman-Lehmann syndrome: identification of a
      novel de novo PHF6 mutation in a female patient.
AB  - BACKGROUND: Borjeson-Forssman-Lehmann syndrome (BFLS; MIM 301900) is an
      infrequently described X linked disorder caused by mutations in PHF6, a novel
      zinc finger gene of unknown function. OBJECTIVE: To present the results of
      mutation screening in individuals referred for PHF6 testing and discuss the value
      of prior X-inactivation testing in the mothers of these individuals. RESULTS: 25
      unrelated individuals were screened (24 male, one female). Five PHF6 mutations
      were detected, two of which (c.940A-->G and c.27_28insA) were novel. One of these
      new mutations, c.27_28insA, was identified in a female BFLS patient. This was
      shown to be a de novo mutation arising on the paternal chromosome. This is the
      first report of a clinically diagnosed BFLS female with a confirmed PHF6
      mutation. In addition, the X-inactivation status of the mothers of 19 males with
      suggested clinical diagnosis of BFLS was determined. Skewed (> or =70%) X
      inactivation was present in five mothers, three of whom had sons in whom a PHF6
      mutation was detected. The mutation positive female also showed skewing.
      CONCLUSIONS: The results indicate that the success of PHF6 screening in males
      suspected of having BFLS is markedly increased if there is a positive family
      history and/or skewed X-inactivation is found in the mother.

PMID- 15994864
TI  - Update on the Manchester Scoring System for BRCA1 and BRCA2 testing.

PMID- 15994863
TI  - Ehlers-Danlos syndrome and periventricular nodular heterotopia in a Spanish
      family with a single FLNA mutation.
AB  - BACKGROUND: The Ehlers-Danlos syndrome (EDS) comprises a group of hereditary
      connective tissue disorders. Periventricular nodular heterotopia (PNH) is a human
      neuronal migration disorder characterised by seizures and conglomerates of neural
      cells around the lateral ventricles of the brain, caused by FLNA mutations. FLNA
      encodes filamin A, an actin binding protein involved in cytoskeletal
      organisation. The amino-terminal actin binding domain (ABD) of filamins contains
      two tandem calponin homology domains, CHD1 and CHD2. OBJECTIVE: To report
      clinical and genetic analyses in a Spanish family affected by a connective tissue
      disorder suggestive of EDS type III and PNH. METHODS: A clinical and molecular
      study was undertaken in the three affected women. Clinical histories, physical
      and neurological examinations, brain magnetic resonance imaging studies, and skin
      biopsies were done. Genetic analysis of the FLNA gene was undertaken by direct
      sequencing and restriction fragment length polymorphism analysis. RESULTS:
      Mutation analysis of the FLNA gene resulted in the identification of a novel
      mutation in exon 3 (c.383C-->T) segregating with the combination of both
      syndromes. This mutation results in a substitution of an alanine residue (A128V)
      in CHD1. CONCLUSIONS: The findings suggest that the Ala128Val mutation causes the
      dual EDS-PNH phenotype. This association constitutes a new variant within the EDS
      spectrum. This is the first description of a familial EDS-PNH association with a
      mutation in FLNA.

PMID- 15994865
TI  - Transmission of mutant alleles to female offspring of BRCA1 carriers in Poland.

PMID- 15994866
TI  - Re: Pitfalls of automated comparative sequence analysis as a single platform for
      routine clinical testing for NF1 (Messiaen and Wimmer).

PMID- 15994867
TI  - BRCA1 mutation and neuronal migration defect: implications for chemoprevention.

PMID- 15994868
TI  - Mutations in FLNB cause boomerang dysplasia.
AB  - Boomerang dysplasia (BD) is a perinatal lethal osteochondrodysplasia,
      characterised by absence or underossification of the limb bones and vertebrae.
      The BD phenotype is similar to a group of disorders including atelosteogenesis I,
      atelosteogenesis III, and dominantly inherited Larsen syndrome that we have
      recently shown to be associated with mutations in FLNB, the gene encoding the
      actin binding cytoskeletal protein, filamin B. We report the identification of
      mutations in FLNB in two unrelated individuals with boomerang dysplasia. The
      resultant substitutions, L171R and S235P, lie within the calponin homology 2
      region of the actin binding domain of filamin B and occur at sites that are
      evolutionarily well conserved. These findings expand the phenotypic spectrum
      resulting from mutations in FLNB and underline the central role this protein
      plays during skeletogenesis in humans.

PMID- 15994869
TI  - Association of a COL1A1 polymorphism with lumbar disc disease in young military
      recruits.
AB  - BACKGROUND: Lumbar disc disease (LDD), one of the most common conditions for
      which patients seek medical care, has been associated with sequence changes of
      the COL genes. COL1A1, however, has not been studied in young patients with LDD;
      COL1A1 polymorphisms have been associated with bone mineral density (BMD) in
      several populations and with LDD in older adults. OBJECTIVE: To study COL1A1
      polymorphisms in young Greek army recruits with LDD. SUBJECTS: These young
      soldiers were diagnosed with early LDD at the time of their presentation to a
      military training site. All patients had radiological confirmation of their
      disease; a control group was also studied. METHODS: Sp1-binding site polymorphism
      of the COL1A1 gene was investigated by standard methods. RESULTS: There was an
      increased frequency of the "ss" genotype (33.3%) in LDD patients; none of the
      controls had this genotype. In addition, a significantly smaller number of
      controls was heterozygotes for this allele. CONCLUSIONS: A previously studied
      sequence change of the regulatory region of the COL1A1 gene, the same as has
      previously been associated with low BMD in many populations and LDD in older
      adults, showed a strong association with LDD in young male soldiers who were
      recently diagnosed with this disease.

PMID- 15994870
TI  - A combination of genetic polymorphisms increases the risk of progressive disease
      in chronic hepatitis C.
AB  - BACKGROUND: There is increasing interest in the influence of host genetic factors
      on hepatic fibrosis, and whether genetic markers can reliably identify subjects
      at risk of developing severe disease. We hypothesised that hepatitis C virus
      (HCV) infected subjects with progressive fibrosis, classified using strict
      criteria based on histology at biopsy in addition to disease duration would be
      more likely to inherit several genetic polymorphisms associated with disease
      progression compared with subjects with a low rate of disease progression.
      METHODS: We examined polymorphisms in eight genes that have been reported to have
      an association with hepatic fibrosis. RESULTS: Associations between polymorphisms
      in six genes and more rapidly progressing fibrosis were observed, with individual
      adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly
      progressing fibrosis and possession of > or =3, > or =4, or > or =5 progression
      associated alleles was determined and the adjusted odds ratios increased with
      increasing number of progression associated alleles (9.1, 15.5, and 24.1,
      respectively). Using logistic regression analysis, a predictive equation was
      developed and tested using a second cohort of patients with rapidly progressing
      fibrosis. The predictive equation correctly classified 80% of patients in this
      second cohort. CONCLUSIONS: This approach may allow determination of a genetic
      profile predictive of rapid disease progression in HCV and identify patients
      warranting more aggressive therapeutic management.

PMID- 15994871
TI  - Significant association between IRF6 820G->A and non-syndromic cleft lip with or
      without cleft palate in the Thai population.
AB  - BACKGROUND: Previous data have shown an association between DNA sequence variants
      in the IRF6 gene and an increased risk of non-syndromic cleft lip with or without
      cleft palate (CL/P) in some populations. OBJECTIVE: To investigate Thai CL/P
      patients and relative for a 820G-->A polymorphism. SUBJECTS: 192 CL/P Thai
      patients, 177 of their mothers, 73 of their fathers, and 278 controls. RESULTS:
      There were significant differences in the frequency distributions of both
      genotypes (p = 0.02) and alleles (p = 0.04) among probands as compared with the
      control group. The odds ratio calculated for the patients having the GG genotype
      compared with the other two genotypes (GA and AA) was 1.67 (95% confidence
      interval, 1.13 to 2.47). This pattern is consistent with a recessive effect of
      the G allele. No association between any of the parents' genotypes and CL/P was
      found. The IRF6 820G-->A was responsible for 16.7% of the genetic contribution to
      CL/P. CONCLUSIONS: The findings confirm that IRF6 820G-->A is associated with
      CL/P.

PMID- 15994872
TI  - Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a
      comprehensive study of 43 Italian families.
AB  - Retinitis pigmentosa is the most common form of retinal degeneration and is
      heterogeneous both clinically and genetically. The autosomal dominant forms
      (ADRP) can be caused by mutations in 12 different genes. This report describes
      the first simultaneous mutation analysis of all the known ADRP genes in the same
      population, represented by 43 Italian families. This analysis allowed the
      identification of causative mutations in 12 of the families (28% of the total).
      Seven different mutations were identified, two of which are novel (458delC and
      6901C-->T (P2301S), in the CRX and PRPF8 genes, respectively). Several novel
      polymorphisms leading to amino acid changes in the FSCN2, NRL, IMPDH1, and RP1
      genes were also identified. Analysis of gene prevalences indicates that the
      relative involvement of the RHO and the RDS genes in the pathogenesis of ADRP is
      less in Italy than in US and UK populations. As causative mutations were not
      found in over 70% of the families analysed, this study suggests the presence of
      further novel genes or sequence elements involved in the pathogenesis of ADRP.

PMID- 15994874
TI  - The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is
      associated with the severity of NF2.
AB  - Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations
      have greater variability in disease severity than NF2 patients with other types
      of mutations; the cause of this variability is unknown. We evaluated genotype
      phenotype correlations, with particular focus on the location of splice site
      mutations, using mutation and clinical information on 831 patients from 528 NF2
      families with identified constitutional NF2 mutations. The clinical
      characteristics examined were age at onset of symptoms of NF2 and number of
      intracranial meningiomas, which are the primary indices of the severity of NF2.
      Two regression models were used to analyse genotype-phenotype correlations.
      People with splice site mutations in exons 1-5 had more severe disease than those
      with splice site mutations in exons 11-15. This result is compatible with studies
      showing that exons 2 and 3 are required for self-association of the amino
      terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in
      transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann
      cell derived tumours.

PMID- 15994875
TI  - Is the Ala12 variant of the PPARG gene an "unthrifty allele"?
AB  - BACKGROUND: The thrifty genotype hypothesis proposes that genetic susceptibility
      to type 2 diabetes results from the positive selection of "thrifty" alleles in
      the past. A corollary of this hypothesis is that genetic variants protecting
      against the development of diabetes are "unthrifty" and thus subject to negative
      selection during human evolution. METHODS: It was assessed whether age estimates
      of the diabetes protective PPARG Ala12 allele indicate effects of natural
      selection. Based on published data from four populations, the date of origin of
      the diabetes protective PPARG Ala12 variant was estimated using both allele
      frequency and linkage disequilibrium (LD) with the C1431T single nucleotide
      polymorphism in exon 6 of the PPARG gene. RESULTS: The best LD based estimate of
      the age of the Ala12 allele gave an average of approximately 32,000 years with a
      maximum upper bound of approximately 58,000 years. Assuming a population with a
      growth rate of r = 0.01 per generation, the frequency based estimate of the age
      of the Ala12 variant gave an average of approximately 27,000 years with a maximum
      upper bound of approximately 42,000 years. DISCUSSION: The similarity of both
      time estimates is consistent with selective equivalence of the diabetes
      protective PPARG Ala12 allele and the diabetes susceptible PPARG Pro12 allele.

PMID- 15994873
TI  - The genetic and molecular bases of monogenic disorders affecting proteolytic
      systems.
AB  - Complete and limited proteolysis represents key events that regulate many
      biological processes. At least 5% of the human genome codes for components of
      proteolytic processes if proteases, inhibitors, and cofactors are taken into
      account. Accordingly, disruption of proteolysis is involved in numerous
      pathological conditions. In particular, molecular genetic studies have identified
      a growing number of monogenic disorders caused by mutations in protease coding
      genes, highlighting the importance of this class of enzymes in development,
      organogenesis, immunity, and brain function. This review provides insights into
      the current knowledge about the molecular genetic causes of these disorders. It
      should be noted that most are due to loss of function mutations, indicating
      absolute requirement of proteolytic activities for normal cellular functions.
      Recent progress in understanding the function of the implicated proteins and the
      disease pathogenesis is detailed. In addition to providing important clues to the
      diagnosis, treatment, and pathophysiology of disease, functional characterisation
      of mutations in proteolytic systems emphasises the pleiotropic functions of
      proteases in the body homeostasis.

PMID- 15994876
TI  - Homozygous mutations in LPIN2 are responsible for the syndrome of chronic
      recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia
      (Majeed syndrome).
AB  - BACKGROUND: Majeed syndrome is an autosomal recessive, autoinflammatory disorder
      characterised by chronic recurrent multifocal osteomyelitis and congenital
      dyserythropoietic anaemia. The objectives of this study were to map, identify,
      and characterise the Majeed syndrome causal gene and to speculate on its function
      and role in skin and bone inflammation. METHODS: Six individuals with Majeed
      syndrome from two unrelated families were identified for this study. Homozygosity
      mapping and parametric linkage analysis were employed for the localisation of the
      gene responsible for Majeed syndrome. Direct sequencing was utilised for the
      identification of mutations within the genes contained in the region of linkage.
      Expression studies and in silico characterisation of the identified causal gene
      and its protein were carried out. RESULTS: The phenotype of Majeed syndrome
      includes inflammation of the bone and skin, recurrent fevers, and
      dyserythropoietic anaemia. The clinical picture of the six affected individuals
      is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on
      chromosome 18p. Examination of genes in this interval led to the identification
      of homozygous mutations in LPIN2 in affected individuals from the two families.
      LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and
      its role in inflammation remains unknown. CONCLUSIONS: We conclude that
      homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the
      aberrant immune response in this condition will shed light on the aetiology of
      other inflammatory disorders of multifactorial aetiology including isolated
      chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

PMID- 15994877
TI  - Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.
AB  - BACKGROUND: Somatically acquired chromosomal translocation is a common mechanism
      of oncogene activation in many haematopoietic tumours and sarcomas. However, very
      few recurrent chromosomal translocations have been reported in more common
      epithelial tumours such as lung carcinomas. METHODS: We established a cell line
      HCC2429 from an aggressive, metastatic lung cancer arising in a young, non
      smoking woman, demonstrating a t(15;19)(q13.2;p13.1). The breakpoints on
      chromosomes 15 and 19 were cloned using long distance inverse PCR and we
      determined by RT-PCR that the translocation results in a novel fusion transcript
      in which the 3' end Brd4 on chromosome 19p is fused to the 5' end of NUT on
      chromosome 15q. RESULTS: In total, 128 lung cancer tissues were screened using
      fluorescent in situ hybridisation, but none of the tumours screened demonstrated
      t(15;19), suggesting that this translocation is not commonly found in lung
      cancer. Consistent with previous literature, ectopic expression of wild type Brd4
      was shown to inhibit G(1) to S progression. However, we also found that the Brd4
      NUT fusion augments the inhibition of progression to S phase compared with wild
      type Brd4. CONCLUSION: Alteration in cell cycle kinetics is important in
      tumorigenesis, although the exact role of Brd4-NUT fusion protein in the
      pathogenesis of lung cancers remains unclear and need to be further elucidated.

PMID- 15994878
TI  - STRA13 expression and subcellular localisation in normal and tumour tissues:
      implications for use as a diagnostic and differentiation marker.
AB  - BACKGROUND: STRA13 is a bHLH transcription factor that plays a crucial role in
      cell differentiation, proliferation, apoptosis, and response to hypoxia.
      OBJECTIVE: To assess STRA13 involvement in carcinogenesis and evaluate its
      diagnostic value. METHODS: A comprehensive analysis was undertaken of the
      endogenous protein expression in 389 normal and corresponding malignant
      specimens, using newly generated polyclonal antibodies. RESULTS: STRA13 was
      commonly expressed in epithelial cells of normal and neoplastic tissues where it
      was confined mostly to the nucleus. Intense cytoplasmic STRA13 immunoreactivity
      was characteristic of myoepithelial and differentiated squamous epithelial cells
      of all organ sites and their neoplastic counterparts, suggesting application of
      STRA13 as a myoepithelial cell marker. A distinctive apical granular cytoplasmic
      staining pattern observed in the pancreas and large intestine was retained in
      corresponding metastatic carcinomas, providing for identification of the primary
      sites of these disseminating tumours. In less differentiated tumours there was a
      tendency to lose the cytoplasmic staining or to switch to nuclear STRA13
      staining. Analysis of STRA13, HIF-1alpha, and CAIX expression patterns in a large
      set of various tumours substantiated the association of STRA13 with HIF-1alpha
      expression and hypoxia in vivo. Investigation of the molecular mechanisms of
      STRA13 nucleo-cytoplasmic shuttling suggested that STRA13 employs nuclear
      import/export that utilises the NLS/NES motifs situated within the N-terminus and
      in the middle of the protein. CONCLUSIONS: STRA13 may serve as a marker for
      myoepithelial cells, for the degree of tumour differentiation, and for
      identification of the primary site of certain metastatic tumours. In combination
      with CAIX and CAXII markers, it may lead to a more accurate classification of all
      renal carcinomas.

PMID- 15994879
TI  - A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome
      5.
AB  - Patients with hereditary haemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu
      syndrome) have variable presentation patterns and a high risk of preventable
      complications. Diagnostic tests for mutations in endoglin (HHT type 1) and ALK-1
      (HHT type 2) are available. Some HHT patients are now known to have HHT-juvenile
      polyposis overlap syndrome due to Smad4 mutations. Families were ascertained
      following the presentation of probands for embolization of pulmonary
      arteriovenous malformations. Genome-wide linkage studies using over 700
      polymorphic markers, and sequencing of candidate genes, were performed. In a
      previously described HHT family unlinked to endoglin or ALK-1, linkage to Smad4
      was excluded, and no mutations were identified in the endoglin, ALK-1, or Smad4
      genes. Two point LOD scores and recombination mapping identified a 5.4 cM HHT3
      disease gene interval on chromosome 5 in which a single haplotype was inherited
      by all affected members of the pedigree. The remainder of the genome was excluded
      to a 2-5 cM resolution. We are currently studying a further family potentially
      linked to HHT3. We conclude that classical HHT with pulmonary involvement can
      result from mutations in an unidentified gene on chromosome 5. Identification of
      HHT3 should further illuminate HHT pathogenic mechanisms in which aberrant
      transforming growth factor (TGF)-beta signalling is implicated.

PMID- 15994880
TI  - Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice
      and humans.
AB  - BACKGROUND: A recent genetic study in mice and humans revealed the modulatory
      effect of MC1R (melanocortin-1 receptor) gene variants on kappa-opioid receptor
      mediated analgesia. It is unclear whether this gene affects basal pain
      sensitivity or the efficacy of analgesics acting at the more clinically relevant
      mu-opioid receptor. OBJECTIVE: To characterise sensitivity to pain and mu-opioid
      analgesia in mice and humans with non-functional melanocortin-1 receptors.
      METHODS: Comparisons of spontaneous mutant C57BL/6-Mc1r(e/e) mice to C57BL/6
      wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide
      (M6G) analgesia in humans with MC1R variants. RESULTS: C57BL/6-Mc1r(e/e) mutant
      mice and human redheads--both with non-functional MC1Rs--display reduced
      sensitivity to noxious stimuli and increased analgesic responsiveness to the mu
      opioid selective morphine metabolite, M6G. In both species the differential
      analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are
      similar across genotype. CONCLUSIONS: Genotype at MC1R similarly affects pain
      sensitivity and M6G analgesia in mice and humans. These findings confirm the
      utility of cross species translational strategies in pharmacogenetics.

PMID- 15994881
TI  - A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in
      trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non
      syndromic hearing impairment.

PMID- 15994882
TI  - A genome screen of families at high risk for Hodgkin lymphoma: evidence for a
      susceptibility gene on chromosome 4.

PMID- 15994883
TI  - Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG
      and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.
AB  - A recent report estimated the breast cancer risks in carriers of the three
      Ashkenazi founder mutations to be higher than previously published estimates
      derived from population based studies. In an attempt to confirm this, the breast
      and ovarian cancer risks associated with the three Ashkenazi founder mutations
      were estimated using families included in a previous meta-analysis of populatrion
      based studies. The estimated breast cancer risks for each of the founder BRCA1
      and BRCA2 mutations were similar to the corresponding estimates based on all
      BRCA1 or BRCA2 mutations in the meta-analysis. These estimates appear to be
      consistent with the observed prevalence of the mutations in the Ashkenazi Jewish
      population.

PMID- 15994884
TI  - Association of two tumour necrosis factor gene polymorphisms with the incidence
      of severe intraventricular haemorrhage in preterm infants.

PMID- 15994885
TI  - Effect of input resistance voltage-dependency on DC estimate of membrane
      capacitance in cardiac myocytes.
AB  - The measure of membrane capacitance (C(m)) in cardiac myocytes is of primary
      importance as an index of their size in physiological and pathological
      conditions, and for the understanding of their excitability. Although a plethora
      of very accurate methods has been developed to access C(m) value in single cells,
      cardiac electrophysiologists still use, in the majority of laboratories,
      classical direct current techniques as they have been established in the early
      days of cardiac cellular electrophysiology. These techniques are based on the
      assumption that cardiac membrane resistance (R(m)) is constant, or changes
      negligibly, in a narrow potential range around resting potential. Using patch
      clamp whole-cell recordings, both in current-clamp and voltage-clamp conditions,
      and numerical simulations, we document here the voltage-dependency of R(m), up to
      -45% of its resting value for 10-mV hyperpolarization, in resting rat ventricular
      myocytes. We show how this dependency makes classical protocols to misestimate
      C(m) in a voltage-dependent manner (up to 20% errors), which can dramatically
      affect C(m)-based calculations on cell size and on intracellular ion dynamics. We
      develop a simple mechanistic model to fit experimental data and obtain voltage
      independent estimates of C(m), and we show that accurate estimates can also be
      extrapolated from the classical approach.

PMID- 15994886
TI  - From continuum Fokker-Planck models to discrete kinetic models.
AB  - Two theoretical formalisms are widely used in modeling mechanochemical systems
      such as protein motors: continuum Fokker-Planck models and discrete kinetic
      models. Both have advantages and disadvantages. Here we present a "finite volume"
      procedure to solve Fokker-Planck equations. The procedure relates the continuum
      equations to a discrete mechanochemical kinetic model while retaining many of the
      features of the continuum formulation. The resulting numerical algorithm is a
      generalization of the algorithm developed previously by Fricks, Wang, and Elston
      through relaxing the local linearization approximation of the potential
      functions, and a more accurate treatment of chemical transitions. The new
      algorithm dramatically reduces the number of numerical cells required for a
      prescribed accuracy. The kinetic models constructed in this fashion retain some
      features of the continuum potentials, so that the algorithm provides a systematic
      and consistent treatment of mechanical-chemical responses such as load-velocity
      relations, which are difficult to capture with a priori kinetic models. Several
      numerical examples are given to illustrate the performance of the method.

PMID- 15994887
TI  - Kinetics of protein adsorption and desorption on surfaces with grafted polymers.
AB  - The kinetics of protein adsorption are studied using a generalized diffusion
      approach which shows that the time-determining step in the adsorption is the
      crossing of the kinetic barrier presented by the polymers and already adsorbed
      proteins. The potential of mean-force between the adsorbing protein and the
      polymer-protein surface changes as a function of time due to the deformation of
      the polymer layers as the proteins adsorb. Furthermore, the range and strength of
      the repulsive interaction felt by the approaching proteins increases with grafted
      polymer molecular weight and surface coverage. The effect of molecular weight on
      the kinetics is very complex and different than its role on the equilibrium
      adsorption isotherms. The very large kinetic barriers make the timescale for the
      adsorption process very long and the computational effort increases with time,
      thus, an approximate kinetic approach is developed. The kinetic theory is based
      on the knowledge that the time-determining step is crossing the potential-of-mean
      force barrier. Kinetic equations for two states (adsorbed and bulk) are written
      where the kinetic coefficients are the product of the Boltzmann factor for the
      free energy of adsorption (desorption) multiplied by a preexponential factor
      determined from a Kramers-like theory. The predictions from the kinetic approach
      are in excellent quantitative agreement with the full diffusion equation
      solutions demonstrating that the two most important physical processes are the
      crossing of the barrier and the changes in the barrier with time due to the
      deformation of the polymer layer as the proteins adsorb/desorb. The kinetic
      coefficients can be calculated a priori allowing for systematic calculations over
      very long timescales. It is found that, in many cases where the equilibrium
      adsorption shows a finite value, the kinetics of the process is so slow that the
      experimental system will show no adsorption. This effect is particularly
      important at high grafted polymer surface coverage. The construction of
      guidelines for molecular weight/surface coverage necessary for kinetic prevention
      of protein adsorption in a desired timescale is shown. The time-dependent
      desorption is also studied by modeling how adsorbed proteins leave the surface
      when in contact with a pure water solution. It is found that the kinetics of
      desorption are very slow and depend in a nonmonotonic way in the polymer chain
      length. When the polymer layer thickness is shorter than the size of the protein,
      increasing polymer chain length, at fixed surface coverage, makes the desorption
      process faster. For polymer layers with thickness larger than the protein size,
      increases in molecular weight results in a longer time for desorption. This is
      due to the grafted polymers trapping the adsorbed proteins and slowing down the
      desorption process. These results offer a possible explanation to some
      experimental data on adsorption. Limitations and extension of the developed
      approaches for practical applications are discussed.

PMID- 15994888
TI  - Potentials of mean force for the interaction of blocked alanine dipeptide
      molecules in water and gas phase from MD simulations.
AB  - We calculate potentials of mean force (PMFs) for the intermolecular interaction
      of two blocked alanine dipeptide (AcAlaNHMe) molecules in water and gas phase at
      two temperatures, 278 and 300 K, from all-atom molecular dynamics simulations.
      Simple models based on buried solvent accessible surface and one-dimensional
      potentials derived from distance-based radial distribution functions are not
      capable of expressing the short- and long-range complexity of the solute-solute
      interactions in water. Instead, radial and angular variations in the PMFs are
      observed with the two-dimensional potentials. The strength of the interactions
      for specific relative orientations of the molecules in the two-dimensional PMFs
      is more than double that observed in the one-dimensional PMFs. The populations of
      specific blocked alanine dipeptide conformations in water, such as alpha(R) and
      PPII, vary with temperature, and most significantly, with the distance between
      the centers of mass. A preference for helical conformations is observed at close
      encounter between molecules.

PMID- 15994889
TI  - How noise and coupling induce bursting action potentials in pancreatic {beta}
      cells.
AB  - Unlike isolated beta-cells, which usually produce continuous spikes or fast and
      irregular bursts, electrically coupled beta-cells are apt to exhibit robust
      bursting action potentials. We consider the noise induced by thermal fluctuations
      as well as that by channel-gating stochasticity and examine its effects on the
      action potential behavior of the beta-cell model. It is observed numerically that
      such noise in general helps single cells to produce a variety of electrical
      activities. In addition, we also probe coupling via gap junctions between
      neighboring cells, with heterogeneity induced by noise, to find that it enhances
      regular bursts.

PMID- 15994890
TI  - Observation volumes and {gamma}-factors in two-photon fluorescence fluctuation
      spectroscopy.
AB  - Fluorescence fluctuation spectroscopy has become an important measurement tool
      for investigating molecular dynamics, molecular interactions, and chemical
      kinetics in biological systems. Although the basic theory of fluctuation
      spectroscopy is well established, it is not widely recognized that saturation of
      the fluorescence excitation can dramatically alter the size and profile of the
      fluorescence observation volume from which fluorescence fluctuations are
      measured, even at relatively modest excitation levels. A precise model for these
      changes is needed for accurate analysis and interpretation of fluctuation
      spectroscopy data. We here introduce a combined analytical and computational
      approach to characterize the observation volume under saturating conditions and
      demonstrate how the variation in the volume is important in two-photon
      fluorescence correlation spectroscopy. We introduce a simple approach for
      analysis of fluorescence correlation spectroscopy data that can fully account for
      the effects of saturation, and demonstrate its success for characterizing the
      observed changes in both the amplitude and relaxation timescale of measured
      correlation curves. We also discuss how a quantitative model for the observed
      phenomena may be of broader importance in fluorescence fluctuation spectroscopy.

PMID- 15994891
TI  - Accessibility of nitroxide side chains: absolute Heisenberg exchange rates from
      power saturation EPR.
AB  - In site-directed spin labeling, the relative solvent accessibility of spin
      labeled side chains is taken to be proportional to the Heisenberg exchange rate
      (W(ex)) of the nitroxide with a paramagnetic reagent in solution. In turn,
      relative values of W(ex) are determined by continuous wave power saturation
      methods and expressed as a proportional and dimensionless parameter Pi. In the
      experiments presented here, NiEDDA is characterized as a paramagnetic reagent for
      solvent accessibility studies, and it is shown that absolute values of W(ex) can
      be determined from Pi, and that the proportionality constant relating them is
      independent of the paramagnetic reagent and mobility of the nitroxide. Based on
      absolute exchange rates, an accessibility factor is defined (0 < rho < 1) that
      serves as a quantitative measure of side-chain solvent accessibility. The
      accessibility factors for a nitroxide side chain at 14 different sites in T4
      lysozyme are shown to correlate with a structure-based accessibility parameter
      derived from the crystal structure of the protein. These results provide a useful
      means for relating crystallographic and site-directed spin labeling data, and
      hence comparing crystal and solution structures.

PMID- 15994892
TI  - Accessibility and dynamics of nitroxide side chains in T4 lysozyme measured by
      saturation recovery EPR.
AB  - Long pulse saturation recovery electron paramagnetic resonance spectroscopy is
      applied to the investigation of spin-labeled side chains placed along a regular
      helix extending from 128 to 135 in T4 lysozyme. Under an argon atmosphere,
      analysis of the exponential saturation recovery curves gives the spin-lattice
      relaxation rates of the nitroxides, which depend on the nitroxide side-chain
      dynamics. In the presence of the fast-relaxing paramagnetic reagents O(2) or
      NiEDDA, global analysis of the saturation recovery provides the spin-lattice
      relaxation rates as well as the Heisenberg exchange rates of the nitroxide with
      the reagents. As previously shown with power saturation methods, such exchange
      rates are direct measures of the solvent accessibility of the nitroxide side
      chains in the protein structure. The periodic dependence of the spin-lattice
      relaxation rates and the exchange rates along the 128-135 sequence reveal the
      presence of the helical structure, demonstrating the use of these parameters in
      structure determination. In general, multiple exponentials are required to fit
      the saturation recovery data, thus identifying multiple states of the side chain.
      In one case, multiple conformations detected in the spectrum are not evident in
      the saturation recovery, suggesting rapid exchange on the timescale of spin
      lattice relaxation.

PMID- 15994893
TI  - Transition from stochastic to deterministic behavior in calcium oscillations.
AB  - Simulation and modeling is becoming more and more important when studying complex
      biochemical systems. Most often, ordinary differential equations are employed for
      this purpose. However, these are only applicable when the numbers of
      participating molecules in the biochemical systems are large enough to be treated
      as concentrations. For smaller systems, stochastic simulations on discrete
      particle basis are more accurate. Unfortunately, there are no general rules for
      determining which method should be employed for exactly which problem to get the
      most realistic result. Therefore, we study the transition from stochastic to
      deterministic behavior in a widely studied system, namely the signal transduction
      via calcium, especially calcium oscillations. We observe that the transition
      occurs within a range of particle numbers, which roughly corresponds to the
      number of receptors and channels in the cell, and depends heavily on the
      attractive properties of the phase space of the respective systems dynamics. We
      conclude that the attractive properties of a system, expressed, e.g., by the
      divergence of the system, are a good measure for determining which simulation
      algorithm is appropriate in terms of speed and realism.

PMID- 15994894
TI  - Influence of the water structure on the acetylcholinesterase efficiency.
AB  - We have studied the catalytic efficiency of acetylcholinesterase (AChE) in
      various solutions with ion-disturbed water structure to explore the role that the
      water structure plays in the substrate-enzyme encounter. The extent of water
      structuring in the different aqueous solutions was determined by near-infrared
      spectroscopy. The influence of water structure on the degree of solvation and on
      the intramolecular mobility of AChE was investigated for different aqueous ionic
      solutions by small-angle x-ray scattering technique and depolarization
      fluorescence spectroscopy. It was found that the encounter process between AChE
      and acetylthiocholine was promoted in solutions with less structured water. In
      these solutions it was also found that AChE is less solvated coinciding with
      higher intramolecular mobility. The found experimental results suggest that the
      water structure may influence the substrate-enzyme encounter process by
      diminishing the AChE solvation shell and may help diffusion of the substrate
      through the gorge by enhancing the intramolecular mobility of AChE.

PMID- 15994895
TI  - Quantifying kinetic paths of protein folding.
AB  - We propose a new approach to activated protein folding dynamics via a diffusive
      path integral framework. The important issues of kinetic paths in this situation
      can be directly addressed. This leads to the identification of the kinetic paths
      of the activated folding process, and provides a direct tool and language for the
      theoretical and experimental community to understand the problem better. The
      kinetic paths giving the dominant contributions to the long-time folding
      activation dynamics can be quantitatively determined. These are shown to be the
      instanton paths. The contributions of these instanton paths to the kinetics lead
      to the "bell-like" shape folding rate dependence on temperature, which is in good
      agreement with folding kinetic experiments and simulations. The connections to
      other approaches as well as the experiments of the protein folding kinetics are
      discussed.

PMID- 15994896
TI  - Comparison of the light-harvesting networks of plant and cyanobacterial
      photosystem I.
AB  - With the availability of structural models for photosystem I (PSI) in
      cyanobacteria and plants it is possible to compare the excitation transfer
      networks in this ubiquitous photosystem from two domains of life separated by
      over one billion years of divergent evolution, thus providing an insight into the
      physical constraints that shape the networks' evolution. Structure-based modeling
      methods are used to examine the excitation transfer kinetics of the plant PSI
      LHCI supercomplex. For this purpose an effective Hamiltonian is constructed that
      combines an existing cyanobacterial model for structurally conserved chlorophylls
      with spectral information for chlorophylls in the Lhca subunits. The plant PSI
      excitation migration network thus characterized is compared to its cyanobacterial
      counterpart investigated earlier. In agreement with observations, an average
      excitation transfer lifetime of approximately 49 ps is computed for the plant PSI
      LHCI supercomplex with a corresponding quantum yield of 95%. The sensitivity of
      the results to chlorophyll site energy assignments is discussed. Lhca subunits
      are efficiently coupled to the PSI core via gap chlorophylls. In contrast to the
      chlorophylls in the vicinity of the reaction center, previously shown to optimize
      the quantum yield of the excitation transfer process, the orientational ordering
      of peripheral chlorophylls does not show such optimality. The finding suggests
      that after close packing of chlorophylls was achieved, constraints other than
      efficiency of the overall excitation transfer process precluded further evolution
      of pigment ordering.

PMID- 15994897
TI  - Theory of electrostatically regulated binding of T4 gene 32 protein to single-
      and double-stranded DNA.
AB  - Bacteriophage T4 gene 32 protein (gp32) is a single-stranded DNA binding protein,
      which is essential for DNA replication, recombination, and repair. In a recent
      article, we described a new method using single DNA molecule stretching
      measurements to determine the noncooperative association constants K(ds) to
      double-stranded DNA for gp32 and *I, a truncated form of gp32. In addition, we
      developed a single molecule method for measuring K(ss), the association constant
      of these proteins to single-stranded DNA. We found that in low salt both K(ds)
      and K(ss) have a very weak salt dependence for gp32, whereas for *I the salt
      dependence remains strong. In this article we propose a model that explains the
      salt dependence of gp32 and *I binding to single-stranded nucleic acids. The main
      feature of this model is the strongly salt-dependent removal of the C-terminal
      domain of gp32 from its nucleic acid binding site that is in pre-equilibrium to
      protein binding to both double-stranded and single-stranded nucleic acid. We
      hypothesize that unbinding of the C-terminal domain is associated with counterion
      condensation of sodium ions onto this part of gp32, which compensates for sodium
      ion release from the nucleic acid upon its binding to the protein. This results
      in the salt-independence of gp32 binding to DNA in low salt. The predictions of
      our model quantitatively describe the large body of thermodynamic and kinetic
      data from bulk and single molecule experiments on gp32 and *I binding to single
      stranded nucleic acids.

PMID- 15994898
TI  - Cofilin, actin and their complex observed in vivo using fluorescence resonance
      energy transfer.
AB  - Actin is the principal component of microfilaments. Its assembly/disassembly is
      essential for cell motility, cytokinesis, and a range of other functions. Recent
      evidence suggests that actin is present in the nucleus where it may be involved
      in the regulation of gene expression and that cofilin binds actin and can
      translocate into the nucleus during times of stress. In this report, we combine
      fluorescence resonance energy transfer and confocal microscopy to analyze the
      interactions of cofilin and G-actin within the nucleus and cytoplasm. By
      measuring the rate of photobleaching of fluorescein-labeled actin in the presence
      and absence of Cy5-labeled cofilin, we determined that almost all G-actin in the
      nucleus is bound to cofilin, whereas approximately (1/2) is bound in the
      cytoplasm. Using fluorescence resonance energy transfer imaging techniques we
      observed that a significant proportion of fluorescein-labeled cofilin in both the
      nucleus and cytoplasm binds added tetramethylrhodamine-labeled G-actin. Our data
      suggest there is significantly more cofilin-G-actin complex and less free cofilin
      in the nucleus than in the cytoplasm.

PMID- 15994899
TI  - X-ray reflectivity studies of cPLA2{alpha}-C2 domains adsorbed onto Langmuir
      monolayers of SOPC.
AB  - X-ray reflectivity is used to study the interaction of C2 domains of cytosolic
      phospholipase A(2) (cPLA(2)alpha-C2) with a Langmuir monolayer of 1-stearoyl-2
      oleoyl-sn-glycero-3-phosphocholine (SOPC) supported on a buffered aqueous
      solution containing Ca(2+). The reflectivity is analyzed in terms of the known
      crystallographic structure of cPLA(2)alpha-C2 domains and a slab model
      representing the lipid layer to yield an electron density profile of the lipid
      layer and bound C2 domains. This new method of analysis determines the angular
      orientation and penetration depth of the cPLA(2)alpha-C2 domains bound to the
      SOPC monolayer, information not available from the standard slab model analysis
      of x-ray reflectivity. The best-fit orientation places the protein-bound Ca(2+)
      ions within 1 A of the lipid phosphate group (with an accuracy of +/-3 A).
      Hydrophobic residues of the calcium-binding loops CBL1 and CBL3 penetrate deepest
      into the lipid layer, with a 2 A penetration into the tailgroup region. X-ray
      measurements with and without the C2 domain indicate that there is a loss of
      electrons in the headgroup region of the lipid monolayer upon binding of the
      domains. We suggest that this is due to a loss of water molecules bound to the
      headgroup. Control experiments with a non-calcium buffer and with domain mutants
      confirm that the cPLA(2)alpha-C2 binding to the SOPC monolayer is Ca(2+)
      dependent and that the hydrophobic residues in the calcium-binding loops are
      critical for membrane binding. These results indicate that an entropic component
      (due to water loss) as well as electrostatic and hydrophobic interactions
      contributes to the binding mechanism.

PMID- 15994900
TI  - Probing conformational disorder in neurotensin by two-dimensional solid-state NMR
      and comparison to molecular dynamics simulations.
AB  - An approach is introduced to characterize conformational ensembles of
      intrinsically unstructured peptides on the atomic level using two-dimensional
      solid-state NMR data and their combination with molecular dynamics simulations.
      For neurotensin, a peptide that binds with high affinity to a G-protein coupled
      receptor, this method permits the investigation of the changes in conformational
      preferences of a neurotransmitter transferred from a frozen aqueous solution via
      a lipid model phase to the receptor-bound form. The results speak against a
      conformational pre-organization of the ligand in detergents in which the receptor
      has been shown to be functional. Further extensions to the study of protein
      folding are possible.

PMID- 15994901
TI  - Direct visualization of membrane leakage induced by the antibiotic peptides:
      maculatin, citropin, and aurein.
AB  - Membrane lysis caused by antibiotic peptides is often rationalized by means of
      two different models: the so-called carpet model and the pore-forming model. We
      report here on the lytic activity of antibiotic peptides from Australian tree
      frogs, maculatin 1.1, citropin 1.1, and aurein 1.2, on POPC or POPC/POPG model
      membranes. Leakage experiments using fluorescence spectroscopy indicated that the
      peptide/lipid mol ratio necessary to induce 50% of probe leakage was smaller for
      maculatin compared with aurein or citropin, regardless of lipid membrane
      composition. To gain further insight into the lytic mechanism of these peptides
      we performed single vesicle experiments using confocal fluorescence microscopy.
      In these experiments, the time course of leakage for different molecular weight
      (water soluble) fluorescent markers incorporated inside of single giant
      unilamellar vesicles is observed after peptide exposure. We conclude that
      maculatin and its related peptides demonstrate a pore-forming mechanism
      (differential leakage of small fluorescent probe compared with high molecular
      weight markers). Conversely, citropin and aurein provoke a total membrane
      destabilization with vesicle burst without sequential probe leakage, an effect
      that can be assigned to a carpeting mechanism of lytic action. Additionally, to
      study the relevance of the proline residue on the membrane-action properties of
      maculatin, the same experimental approach was used for maculatin-Ala and
      maculatin-Gly (Pro-15 was replaced by Ala or Gly, respectively). Although a
      similar peptide/lipid mol ratio was necessary to induce 50% of leakage for POPC
      membranes, the lytic activity of maculatin-Ala and maculatin-Gly decreased in
      POPC/POPG (1:1 mol) membranes compared with that observed for the naturally
      occurring maculatin sequence. As observed for maculatin, the lytic action of
      Maculatin-Ala and maculatin-Gly is in keeping with the formation of pore-like
      structures at the membrane independently of lipid composition.

PMID- 15994902
TI  - Side-dependent inhibition of a prokaryotic ClC by DIDS.
AB  - The x-ray structure of the Escherichia coli chloride/proton antiporter ClC-ec1
      provides a structural paradigm for the widespread and diverse ClC family of
      chloride channels and transporters. To maximize the usefulness of this paradigm,
      it is important to directly relate structure to function via studies of ClC-ec1
      itself; however, few functional studies of this protein have been performed. In
      an endeavor to develop new tools for functional analysis of ClC-ec1, we have
      discovered that this transporter is inhibited by the stilbenedisulfonate 4,4
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In planar lipid bilayers,
      DIDS inhibits ClC-ec1 activity reversibly, with an apparent affinity in the
      micromolar range. Since ClC-ec1 is randomly oriented in the bilayers,
      ascertaining whether DIDS inhibits from the intracellular or extracellular side
      required an indirect approach. Using the ClC-ec1 structure as a guide, we
      designed a strategy in which modification of Y445C was monitored in conjunction
      with inhibition by DIDS. We found that DIDS inhibits transporters specifically
      from the intracellular side. Transporters with their extracellular side exposed
      to DIDS function normally, maintaining stoichiometric proton/chloride antiport
      over a wide range of proton and chloride concentrations. The side-dependent
      nature of DIDS inhibition will be useful for generating "functionally oriented"
      preparations of ClC-ec1, in which DIDS is used to silence transporters in one
      orientation but not the other.

PMID- 15994903
TI  - Influence of the long-chain/short-chain amphiphile ratio on lateral diffusion of
      PEG-lipid in magnetically aligned lipid bilayers as measured via pulsed-field
      gradient NMR.
AB  - Lateral diffusion measurements of polyethylene glycol(PEG)-lipid incorporated
      into magnetically aligned lipid bilayers, composed of dimyristoyl
      phosphatidylcholine (DMPC) plus dihexanoyl phosphatidylcholine (DHPC) plus 1 mol
      % (relative to DMPC) dimyristoyl phosphatidylethanolamine-n-[methoxy(polyethylene
      glycol)-2000] (DMPE-PEG 2000), were performed using stimulated-echo pulsed-field
      gradient proton ((1)H) nuclear magnetic resonance spectroscopy. The DMPE-PEG 2000
      (1 mol %, 35 degrees C) lateral diffusion coefficient D varied directly with the
      mole fraction of DMPC, X(DMPC) = q/(1+q) where q = DMPC/DHPC molar ratio,
      decreasing progressively from D = 1.65 x 10(-11) m(2) s(-1) at q approximately
      4.7 to D = 0.65 x 10(-11) m(2) s(-1) at q approximately 2.5. Possible sources of
      this dependence, including orientational disorder, obstruction, and PEG-lipid
      sequestration, were simulated using, respectively, a diffusion-in-a-cone model,
      percolation theory, and a two-phase PEG distribution model. Orientational
      disorder alone was not capable of reproducing the observations, but in
      combination with either obstruction or PEG-lipid two-phase distribution models
      did so satisfactorily. A combination of all three models yielded the most
      reasonable fit to the observed dependence of lateral diffusion on q. These same
      effects would be expected to influence lateral diffusion of any bilayer
      associating species in such systems.

PMID- 15994904
TI  - Tracking unfolding and refolding of single GFPmut2 molecules.
AB  - The unfolding and refolding kinetics of >600 single GFPmut2 molecules, entrapped
      in wet nanoporous silica gels, were followed by monitoring simultaneously the
      fluorescence emission of the anionic and neutral state of the chromophore, primed
      by two-photon excitation. The rate of unfolding, induced by guanidinium chloride,
      was determined by counting the number of single molecules that disappear in
      fluorescence images, under conditions that do not cause bleaching or photoinduced
      conversion between chromophore protonation states. The unfolding rate is of the
      order of 0.01 min(-1), and its dependence on denaturant concentration is very
      similar to that previously reported for high protein load gels. Upon rinsing the
      gels with denaturant-free buffer, the GFPmut2 molecules refold with rates >10
      min(-1), with an apparently random distribution between neutral and anionic
      states, that can be very different from the preunfolding equilibrium. A
      subsequent very slow (lifetime of approximately 70 min) relaxation leads to the
      equilibrium distribution of the protonation states. This mechanism, involving one
      or more native-like refolding intermediates, is likely rate limited by
      conformational rearrangements that are undetectable in circular dichroism
      experiments. Several unfolding/refolding cycles can be followed on the same
      molecules, indicating full reversibility of the process and, noticeably, a bias
      of denaturated molecules toward refolding in the original protonation state.

PMID- 15994905
TI  - Areas of molecules in membranes consisting of mixtures.
AB  - The question has arisen in recent literature: how to partition the total area in
      simulations of membranes consisting of more than one kind of molecule into
      average areas for each kind of molecule. Several definitions have been proposed,
      each of which has arbitrary features. When applied to mixtures of cholesterol and
      DPPC, these definitions give different results. This note recalls that physical
      chemistry provides a canonical way to define molecular area, in analogy to the
      definition of partial-specific volume. Results for partial-specific area are
      obtained from simulations of DPPC/cholesterol bilayers and compared to the
      results from the other recent definitions. The partial-specific-area formalism
      dramatically demonstrates the condensing effect of cholesterol and this leads to
      the introduction of a specific model that accounts for the area of mixtures of
      cholesterol and lipid over the entire range of cholesterol concentrations.

PMID- 15994906
TI  - Novel and mechanical stress-responsive MicroRNAs in Populus trichocarpa that are
      absent from Arabidopsis.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs that can play crucial regulatory
      roles in eukaryotes by targeting mRNAs for silencing. To test whether miRNAs play
      roles in the regulation of wood development in tree species, we isolated small
      RNAs from the developing xylem of Populus trichocarpa stems and cloned 22 miRNAs.
      They are the founding members of 21 miRNA gene families for 48 miRNA sequences,
      represented by 98 loci in the Populus genome. A majority of these miRNAs were
      predicted to target developmental- and stress/defense-related genes and possible
      functions associated with the biosynthesis of cell wall metabolites. Of the 21 P.
      trichocarpa miRNA families, 11 have sequence conservation in Arabidopsis thaliana
      but exhibited species-specific developmental expression patterns, suggesting that
      even conserved miRNAs may have different regulatory roles in different species.
      Most unexpectedly, the remaining 10 miRNAs, for which 17 predicted targets were
      experimentally validated in vivo, are absent from the Arabidopsis genome,
      suggesting possible roles in tree-specific processes. In fact, the expression of
      a majority of the cloned miRNAs was upregulated or downregulated in woody stems
      in a manner consistent with tree-specific corrective growth against tension and
      compression stresses, two constant mechanical loads in trees. Our results show
      that plant miRNAs can be induced by mechanical stress and may function in one of
      the most critical defense systems for structural and mechanical fitness.

PMID- 15994907
TI  - Pyruvate decarboxylase provides growing pollen tubes with a competitive advantage
      in petunia.
AB  - Rapid pollen tube growth places unique demands on energy production and
      biosynthetic capacity. The aim of this work is to understand how primary
      metabolism meets the demands of such rapid growth. Aerobically grown pollen
      produce ethanol in large quantities. The ethanolic fermentation pathway consists
      of two committed enzymes: pyruvate decarboxylase (PDC) and alcohol dehydrogenase
      (ADH). Because adh mutations do not affect male gametophyte function, the obvious
      question is why pollen synthesize an abundant enzyme if they could do just as
      well without. Using transposon tagging in Petunia hybrida, we isolated a null
      mutant in pollen-specific Pdc2. Growth of the mutant pollen tubes through the
      style is reduced, and the mutant allele shows reduced transmission through the
      male, when in competition with wild-type pollen. We propose that not ADH but
      rather PDC is the critical enzyme in a novel, pollen-specific pathway. This
      pathway serves to bypass pyruvate dehydrogenase enzymes and thereby maintain
      biosynthetic capacity and energy production under the unique conditions
      prevailing during pollen-pistil interaction.

PMID- 15994908
TI  - Role of an Arabidopsis AP2/EREBP-type transcriptional repressor in abscisic acid
      and drought stress responses.
AB  - The phytohormone abscisic acid (ABA) modulates the expression of many genes
      important to plant growth and development and to stress adaptation. In this
      study, we found that an APETALA2/EREBP-type transcription factor, AtERF7, plays
      an important role in ABA responses. AtERF7 interacts with the protein kinase
      PKS3, which has been shown to be a global regulator of ABA responses. AtERF7
      binds to the GCC box and acts as a repressor of gene transcription. AtERF7
      interacts with the Arabidopsis thaliana homolog of a human global corepressor of
      transcription, AtSin3, which in turn may interact with HDA19, a histone
      deacetylase. The transcriptional repression activity of AtERF7 is enhanced by
      HDA19 and AtSin3. Arabidopsis plants overexpressing AtERF7 show reduced
      sensitivity of guard cells to ABA and increased transpirational water loss. By
      contrast, AtERF7 and AtSin3 RNA interference lines show increased sensitivity to
      ABA during germination. Together, our results suggest that AtERF7 plays an
      important role in ABA responses and may be part of a transcriptional repressor
      complex and be regulated by PKS3.

PMID- 15994909
TI  - RAC GTPases in tobacco and Arabidopsis mediate auxin-induced formation of
      proteolytically active nuclear protein bodies that contain AUX/IAA proteins.
AB  - Auxin signaling relies on ubiquitin ligase SCF(TIR1)-mediated 26S proteasome
      dependent proteolysis of a large family of short-lived transcription regulators,
      auxin/indole acetic acid (Aux/IAA), resulting in the derepression of auxin
      responsive genes. We have shown previously that a subset of Rac GTPases is
      activated by auxin, and they in turn stimulate auxin-responsive gene expression.
      We show here that increasing Rac signaling activity promotes Aux/IAA degradation,
      whereas downregulating that activity results in the reduction of auxin
      accelerated Aux/IAA proteolysis. Observations reported here reveal a novel
      function for these Rac GTPases as regulators for ubiquitin/26S proteasome
      mediated proteolysis and further consolidate their role in auxin signaling.
      Moreover, our study reveals a cellular process whereby auxin induces and Rac
      GTPases mediate the recruitment of nucleoplasmic Aux/IAAs into proteolytically
      active nuclear protein bodies, into which components of the SCF(TIR1), COP9
      signalosome, and 26S proteasome are also recruited.

PMID- 15994910
TI  - The Rice brassinosteroid-deficient dwarf2 mutant, defective in the rice homolog
      of Arabidopsis DIMINUTO/DWARF1, is rescued by the endogenously accumulated
      alternative bioactive brassinosteroid, dolichosterone.
AB  - We have identified a rice (Oryza sativa) brassinosteroid (BR)-deficient mutant,
      BR-deficient dwarf2 (brd2). The brd2 locus contains a single base deletion in the
      coding region of Dim/dwf1, a homolog of Arabidopsis thaliana DIMINUTO/DWARF1
      (DIM/DWF1). Introduction of the wild-type Dim/dwf1 gene into brd2 restored the
      normal phenotype. Overproduction and repression of Dim/dwf1 resulted in
      contrasting phenotypes, with repressors mimicking the brd2 phenotype and
      overproducers having large stature with increased numbers of flowers and seeds.
      Although brd2 contains low levels of common 6-oxo-type BRs, the severity of the
      brd2 phenotype is much milder than brd1 mutants and most similar to d2 and d11,
      which show a semidwarf phenotype at the young seedling stage. Quantitative
      analysis suggested that in brd2, the 24-methylene BR biosynthesis pathway is
      activated and the uncommon BR, dolichosterone (DS), is produced. DS enhances the
      rice lamina joint bending angle, rescues the brd1 dwarf phenotype, and inhibits
      root elongation, indicating that DS is a bioactive BR in rice. Based on these
      observations, we discuss an alternative BR biosynthetic pathway that produces DS
      when Dim/dwf1 is defective.

PMID- 15994911
TI  - The formin homology 1 domain modulates the actin nucleation and bundling activity
      of Arabidopsis FORMIN1.
AB  - The organization of actin filaments into large ordered structures is a tightly
      controlled feature of many cellular processes. However, the mechanisms by which
      actin filament polymerization is initiated from the available pool of profilin
      bound actin monomers remain unknown in plants. Because the spontaneous
      polymerization of actin monomers bound to profilin is inhibited, the intervention
      of an actin promoting factor is required for efficient actin polymerization. Two
      such factors have been characterized from yeasts and metazoans: the Arp2/3
      complex, a complex of seven highly conserved subunits including two actin-related
      proteins (ARP2 and ARP3), and the FORMIN family of proteins. The recent finding
      that Arabidopsis thaliana plants lacking a functional Arp2/3 complex exhibit
      rather modest morphological defects leads us to consider whether the large FORMIN
      family plays a central role in the regulation of actin polymerization. Here, we
      have characterized the mechanism of action of Arabidopsis FORMIN1 (AFH1).
      Overexpression of AFH1 in pollen tubes has been shown previously to induce
      abnormal actin cable formation. We demonstrate that AFH1 has a unique behavior
      when compared with nonplant formins. The activity of the formin homology domain 2
      (FH2), containing the actin binding activity, is modulated by the formin homology
      domain 1 (FH1). Indeed, the presence of the FH1 domain switches the FH2 domain
      from a tight capper (Kd approximately 3.7 nM) able to nucleate actin filaments
      that grow only in the pointed-end direction to a leaky capper that allows barbed
      end elongation and efficient nucleation of actin filaments from actin monomers
      bound to profilin. Another exciting feature of AFH1 is its ability to bind to the
      side and bundle actin filaments. We have identified an actin nucleator that is
      able to organize actin filaments directly into unbranched actin filament bundles.
      We suggest that AFH1 plays a central role in the initiation and organization of
      actin cables from the pool of actin monomers bound to profilin.

PMID- 15994912
TI  - Microbubble destruction with ultrasound augments neovascularisation by bone
      marrow cell transplantation in rat hind limb ischaemia.
AB  - OBJECTIVE: To examine the effects of microbubble destruction with ultrasound (MB)
      combined with bone marrow derived mononuclear cell transplantation (BMT) into
      ischaemic tissues in rat hind limb ischaemia. METHODS AND RESULTS: Unilateral
      hind limb ischaemia was surgically induced in Lewis rats. At postoperative day 7,
      rats were randomly divided into three groups: a vehicle treated group, an
      ultrasound treated group, and an MB treated group. MB treatment increased
      vascular endothelial growth factor mRNA as assessed by real time polymerase chain
      reaction (3.0-fold, p < 0.05). At four weeks, the MB group had increases in laser
      Doppler blood flow index (LDBFI; 1.2-fold, p < 0.05), angiographically detectable
      collateral vessels (angiographic score: 1.4-fold, p < 0.01), and capillary to
      muscle fibre ratio (1.4-fold, p < 0.01) in ischaemic limbs compared with the
      vehicle treated group. No differences were seen between the vehicle and
      ultrasound treated groups. Secondly, rats were allocated to vehicle treatment,
      BMT (5 x 10(6) cells/rat), or a combination of MB and BMT (MB+BMT) at seven days
      after hind limb ischaemia. BMT treatment significantly increased LDBFI,
      angiographic score, and capillary to muscle fibre ratio compared with vehicle
      treatment. Interestingly, MB+BMT treatment produced significantly greater LDBFI
      (1.2-fold, p < 0.01), angiographic score (1.5-fold, p < 0.01), and capillary to
      muscle fibre ratio (1.5-fold, p < 0.05) than BMT treatment alone. CONCLUSIONS: MB
      may be a useful technique to enhance BMT induced neovascularisation.

PMID- 15994913
TI  - Off pump coronary artery bypass surgery for significant left ventricular
      dysfunction: safety, feasibility, and trends in methodology over time--an early
      experience.
AB  - OBJECTIVE: To examine the safety and applicability of off pump coronary artery
      bypass surgery (OPCAB) in patients with significant left ventricular dysfunction
      and to discuss the clinical implications for the surgical methods. DESIGN:
      Retrospective study. SETTING: Tertiary care university affiliated referral
      centre. PARTICIPANTS: 353 consecutive patients with preoperative left ventricular
      ejection fraction < or = 35% who underwent coronary artery bypass over a three
      year period. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality.
      METHODS: 144 patients operated by OPCAB were compared with 209 patients operated
      by conventional coronary artery bypass. Multivariate and univariate analyses were
      performed on the pre- and postoperative variables to predict risk factors
      associated with hospital morbidity and mortality. RESULTS: Patients in the OPCAB
      group were more likely to be women and to have congestive heart failure, chronic
      obstructive pulmonary disease, hypertension, and diabetes; patients in the on
      pump group were more likely to have had a recent myocardial infarction and to
      have more severe angina pectoris and an urgent/emergent status. The groups did
      not differ significantly in length of stay, major postoperative complication
      rates, or mortality. Comparison of the impact of the procedures on surgical
      methods over time showed an increase in the use of OPCAB (13% to 67%), without
      any impact on morbidity or mortality. CONCLUSIONS: OPCAB is feasible and
      applicable for patients with depressed left ventricular function. This high risk
      group can potentially benefit from the off pump approach.

PMID- 15994914
TI  - PAI-1 and homocysteine, but not lipoprotein (a) and thrombophilic polymorphisms,
      are independently associated with the occurrence of major adverse cardiac events
      after successful coronary stenting.
AB  - OBJECTIVE: To evaluate the role of factor V Leiden, prothrombin G20210A
      polymorphism, plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism,
      PAI-1, homocysteine, and lipoprotein (a) (Lp(a)) in the occurrence of major
      adverse cardiac events (MACE) in patients with acute coronary syndromes who
      underwent coronary stenting. DESIGN: 520 patients (375 men and 145 women) with
      acute coronary syndromes and 520 age and sex matched controls were enrolled. MACE
      were recorded for 109 patients. Heterozygosity for factor V Leiden, prothrombin
      G20210A polymorphism, and 4G/5G polymorphism did not significantly differ between
      patients with and without MACE. A significantly higher percentage of patients
      with increased homocysteine (28% v 19%, p < 0.001) and PAI-1 concentrations (25%
      v 16%, p < 0.001) had MACE with respect to those who did not. In Kaplan-Meier
      survival analysis, the overall risk of MACE was significantly higher among
      patients with increased PAI-1 (p = 0.006) and homocysteine concentrations (p =
      0.04). Cox regression analysis adjusted for age, sex, traditional cardiovascular
      risk factors, renal function, systolic left ventricular function, the number of
      stenosed vessels, and history of percutaneous coronary intervention or coronary
      artery bypass grafting showed that homocysteine (odds ratio 7.5, 95% confidence
      interval (CI) 1.1 to 57.7, p < 0.05) and PAI-1 concentrations (odds ratio 5.3,
      95% CI 1.2 to 23.8, p < 0.05) within the fifth quintile (with respect to the
      first) were significant and independent risk factors for the future occurrence of
      MACE. CONCLUSIONS: Increased PAI-1 and homocysteine concentrations are
      independent risk factors for MACE after successful coronary stenting, whereas
      Lp(a) and thrombophilic polymorphisms are not predictive.

PMID- 15994915
TI  - A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular
      explanation to clinical effect.
AB  - In a recent article, a candidate pathway approach was taken to try to identify
      single nucleotide polymorphisms (SNP) that make up the genetic variation, which
      underlies the phenotypic variation seen between individuals in their
      susceptibility to cancer and the progression of their disease. The p53 stress
      response pathway was chosen given its well-documented importance in tumor
      suppression. A SNP was found which associates with the attenuation of the p53
      pathway and the acceleration of tumor formation in humans and data was presented
      which describe a molecular mechanism for these phenotypes.

PMID- 15994916
TI  - Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway.
AB  - Emerging evidence suggests that the proapoptotic kinase mammalian sterile 20-like
      kinase 2 (MST2) acts in a novel tumor suppression pathway. Recently, we showed
      that Raf-1 kinase sequesters and inhibits MST2 and that this event is critical
      for Raf-mediated cell survival. In this review, we summarize Raf control of MST2
      and we outline a novel pathway involving the downstream effector proteins
      Salvador and Warts/Lats that may act to limit the positive effects of Raf-mitogen
      activated protein kinase signaling in cancer cells.

PMID- 15994917
TI  - CDX2 polymorphisms, RNA expression, and risk of colorectal cancer.
AB  - In adult mammals, CDX2 acts as a transcription factor and is expressed in
      intestinal epithelial cells. Down-regulation of CDX2 is frequently observed in
      colorectal cancer, suggesting its loss may cause dedifferentiation of
      gastrointestinal epithelial cells. However, it is not clear whether inherited
      variants of CDX2 are associated with risk of colorectal cancer. Using
      epidemiologic data and tumors from a population-based case-control study in
      Israel, we identified novel single nucleotide polymorphisms (SNPs) by
      resequencing 35 cases, compared genotype and haplotype frequencies in 455 matched
      pairs, and characterized the tumor characteristics of all 455 cases by
      microsatellite instability analysis, in addition to a partially overlapping set
      of 201 frozen tumors with expression profiling data (82/201) from the same study.
      Nine polymorphisms were identified in the 35 cases, and none of the SNPs or
      haplotypes were associated with risk of colorectal cancer in the 455 matched
      pairs. These variants were not associated with CDX2 expression in the 83 subjects
      with expression data. We evaluated subject and tumor characteristics in the 201
      subjects with CDX2 tumor expression data. Reduced CDX2 expression was associated
      with tumor location (right sided), poor differentiation, high microsatellite
      instability status, and a positive first-degree family history. We conclude that
      it is unlikely that common CDX2 variants account for a measurable fraction of
      susceptibility to colorectal cancer in this population. However, CDX2 expression
      levels were strongly associated with microsatellite instability and tumor
      location in the gastrointestinal tract, consistent with a possible role in the
      specification of gastrointestinal epithelial cell fate in humans.

PMID- 15994918
TI  - Ionizing radiation-induced adenovirus infection is mediated by Dynamin 2.
AB  - Specific viral targeting into intrahepatic tumors remains critical for adenovirus
      gene therapy in liver cancer. We previously showed that ionizing radiation
      increases adenovirus uptake and transgene expression in cells and colon cancer
      xenografts. Here, we tested whether radiation induces viral uptake through virus
      cell membrane interaction. We found that radiation (8 Gy) induced adenoviral gene
      transfer in rat hepatocytes (WB) and human colon carcinoma cells (LoVo). This
      induction (24.4- and 6.5-fold, respectively) and viral uptake were significantly
      diminished by preincubation with antibody for Dynamin 2 but not for Coxsackie
      adenovirus receptor or for integrin alpha(v). Radiation-induced Dynamin 2
      expression was detected by immunohistochemical staining and by increased mRNA
      levels for Dynamin 2 in WB (1.5-fold) and LoVo (2.2-fold) cells. Specific small
      interference RNA (siRNA) transfection significantly inhibited Dynamin 2
      expression in various tumor cell lines (LoVo, D54, and MCF-7) and abolished the
      radiation induction of Dynamin 2. Likewise, radiation-induced viral gene transfer
      in these cells (6.5-, 5.5-, and 9.0-fold, respectively) was significantly reduced
      in siRNA-transfected cells (2.7-, 3.7-, and 5.0-fold, respectively). Moreover,
      viral uptake in LoVo tumor xenografts was significantly increased in s.c. tumors
      (10.9-fold) when adenovirus was given i.v. at 24 hours after tumor irradiation,
      coincident with an elevated Dynamin 2 expression in irradiated tumors. These data
      suggest that ionizing radiation induces adenovirus gene transfer in cells and
      tumor xenografts by regulating viral uptake, potentially through interaction with
      cellular Dynamin 2 and thus should provide insight into improving adenovirus
      targeting in tumors.

PMID- 15994919
TI  - Observation of incipient tumor angiogenesis that is independent of hypoxia and
      hypoxia inducible factor-1 activation.
AB  - It is well established that hypoxia potently stimulates tumor angiogenesis by
      activating hypoxia inducible factor-1 (HIF-1)-induced proangiogenic factors, such
      as vascular endothelial growth factor. However, very little is known about the
      role of hypoxia in incipient angiogenesis in avascular tumors during their early
      stages of growth. To noninvasively investigate the functional significance of
      hypoxia and HIF-1 activation in incipient tumor angiogenesis, we genetically
      engineered HCT116 human colon carcinoma cells and 4T1 mouse mammary carcinoma
      cells with constitutively expressed red fluorescence protein as a tumor marker
      and green fluorescence protein (GFP) as a reporter for hypoxia and HIF-1
      activation. The accuracy of GFP fluorescence in reporting hypoxia was confirmed
      by flow cytometry analysis and by immunohistochemical comparison with
      pimonidazole, a well-established hypoxia marker drug. Mouse dorsal skin-fold
      window chambers showed that incipient angiogenesis preceded a detectable level of
      hypoxia. The detectable levels of hypoxia were spatially and temporally related
      with more intensive secondary angiogenesis following the initial onset of new
      vessel formation. Selective killing of hypoxic cells by tirapazamine efficiently
      eliminated or delayed the detection of hypoxic cells, but it did not
      significantly delay the onset of incipient angiogenesis. These findings provide
      the first in vivo evidence that incipient tumor angiogenesis may not depend on
      hypoxia or HIF-1 activation. This is in contrast to the clear role of hypoxia in
      driving angiogenesis once initial tumor microvessel formation has occurred.

PMID- 15994920
TI  - Isolation and in vitro propagation of tumorigenic breast cancer cells with
      stem/progenitor cell properties.
AB  - Breast cancer-initiating cells have been recently identified in breast carcinoma
      as CD44+/CD24(-/low) cells, which exclusively retain tumorigenic activity and
      display stem cell-like properties. However, at present, direct evidence that
      breast cancer-initiating cells can be propagated in vitro is still lacking. We
      report here the isolation and in vitro propagation of breast cancer-initiating
      cells from three breast cancer lesions and from an established breast carcinoma
      cell line. Our breast carcinoma-derived cultures encompassed undifferentiated
      cells capable of self-renewal, extensive proliferation as clonal nonadherent
      spherical clusters, and differentiation along different mammary epithelial
      lineages (ductal and myoepithelial). Interestingly, cultured cells were
      CD44+/CD24- and Cx43-, overexpressed neoangiogenic and cytoprotective factors,
      expressed the putative stem cell marker Oct-4, and gave rise to new tumors when
      as few as 10(3) cells were injected into the mammary fat pad of SCID mice. Long
      term cultures of breast tumorigenic cells with stem/progenitor cell properties
      represent a suitable in vitro model to study breast cancer-initiating cells and
      to develop therapeutic strategies aimed at eradicating the tumorigenic
      subpopulation within breast cancer.

PMID- 15994922
TI  - Elevated serum levels of CC thymus and activation-related chemokine (TARC) in
      primary Hodgkin's disease: potential for a prognostic factor.
AB  - The CC thymus and activation-related chemokine (TARC) is a protein, which is
      highly expressed by Reed-Sternberg cells in Hodgkin's disease and is found in the
      majority of Hodgkin's disease patients. Within several trials conducted by the
      German Hodgkin study group, 62 Hodgkin's disease patients were elected based on
      availability of serum samples post and prior therapy to assess TARC levels by
      ELISA. TARC levels from 33 patients with continuous complete response (CCR), 20
      patients with relapse, and nine patients with progressive disease (PD) were
      correlated with freedom from treatment failure and survival. As defined in
      healthy donors (mean value +/- 2x SD), a TARC level of >500 pg/mL was considered
      as elevated. The median TARC levels of all patients at baseline and after
      completed primary treatment were 5,803 pg/mL (range, 116-73,074 pg/mL) and 663
      pg/mL (50-24,709 pg/mL), respectively. TARC levels of patients with PD were
      higher than those of patients with CCR at baseline and after therapy. Baseline
      TARC correlated significantly with stage (P = 0.019), erythrocyte sedimentation
      rate (P = 0.004), leukocyte count (P < 0.001), and lymphocyte count (P = 0.026).
      A TARC level of >2,000 pg/mL after completed treatment was a significant risk
      factor for poorer survival (P = 0.02) but not for relapse. In conclusion,
      monitoring serum TARC levels in Hodgkin's disease patients may add valuable
      information about therapy success in Hodgkin's disease patients, especially those
      with PD and should therefore be prospectively evaluated in future trials.

PMID- 15994921
TI  - K-ras codon-specific mutations produce distinctive metabolic phenotypes in NIH3T3
      mice [corrected] fibroblasts.
AB  - Among K-ras mutations, codon 12 mutations have been identified as those
      conferring a more aggressive phenotype. This aggressiveness is primarily
      associated with slow proliferation but greatly increased resistance to apoptosis.
      Using transfected NIH3T3 fibroblasts with a mutated K-ras minigene either at
      codon 12 (K12) or at codon 13 (K13), and taking advantage of [1,2-13C2]glucose
      tracer labeling, we show that codon 12 mutant K-ras (K12)-transformed cells
      exhibit greatly increased glycolysis with only a slight increase in activity
      along pathways that produce nucleic acid and lipid synthesis precursors in the
      oxidative branch of the pentose phosphate pathway and via pyruvate dehydrogenase
      flux. K13 mutants display a modest increase in anaerobic glycolysis associated
      with a large increase in oxidative pentose phosphate pathway activity and
      pyruvate dehydrogenase flux. The distinctive differences in metabolic profiles of
      K12 and K13 codon mutated cells indicate that a strong correlation exists between
      the flow of glucose carbons towards either increased anaerobic glycolysis, and
      resistance to apoptosis (K12), or increased macromolecule synthesis, rapid
      proliferation, and increased sensitivity to apoptosis.

PMID- 15994923
TI  - BLM helicase complements disrupted type II telomere lengthening in telomerase
      negative sgs1 yeast.
AB  - Recombination-mediated pathways for telomere lengthening may be utilized in the
      absence of telomerase activity. The RecQ-like helicases, BLM and Sgs1, are
      implicated in recombination-mediated telomere lengthening in human cells and
      budding yeast, respectively. Here, we show that BLM expression rescues disrupted
      telomere lengthening in telomerase-negative sgs1 yeast. BLM helicase activity is
      required for this complementation, indicating BLM and Sgs1 resolve the same
      telomeric structures. These data support a conserved function for BLM and Sgs1 in
      recombination-mediated telomere lengthening.

PMID- 15994924
TI  - Autocrine platelet-derived growth factor-dependent gene expression in
      glioblastoma cells is mediated largely by activation of the transcription factor
      sterol regulatory element binding protein and is associated with altered genotype
      and patient survival in human brain tumors.
AB  - A complex profile of gene expression elicited by autocrine platelet-derived
      growth factor (PDGF) signaling was identified in U87 MG glioblastoma cells by
      microarray analysis. The most striking pattern observed was a PDGF-dependent
      activation of at least 25 genes involved with biosynthesis and/or uptake of
      cholesterol and isoprenoids, including mevalonate pyrophosphate decarboxylase, 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, and
      low-density lipoprotein receptor. Activity of the HMG-CoA synthase promoter was
      induced by autocrine PDGF activity as indicated by significant reductions
      following forced expression of dominant-negative PDGF-A (88%) or treatment with
      the PDGF receptor antagonist CT52923 (50%). Induction of the HMG-CoA synthase
      promoter required a binding site for sterol regulatory element binding proteins
      (SRE-BP), consistent with a key role for these transcription factors in the
      induction of this gene network. Neither proteolytic activation nor nuclear
      localization of SRE-BP was affected by disruption of the PDGF autocrine loop,
      indicating that PDGF signaling is required for other signaling events involved in
      activation of SRE-BP target genes. Analysis of an expression databank derived
      from human glial tumors (n = 77) identified a subgroup exhibiting a profile
      consistent with PDGF dependence, including increased expression of SRE-BP target
      genes. This subgroup displayed an absence of epidermal growth factor receptor
      gene amplification, decreased incidence of allelic loss of 10q, increased
      frequency of TP53 mutations and allelic losses of 1p and 19q, and longer patient
      survival. This study identifies genes associated with oncogenic activity of PDGF
      and provides important insights into biomarkers and therapeutic targets in
      malignant gliomas.

PMID- 15994925
TI  - Lyn kinase activity is the predominant cellular SRC kinase activity in
      glioblastoma tumor cells.
AB  - Cellular Src activity modulates cell migration, proliferation, and
      differentiation, and recent reports suggest that individual members of the Src
      family may play specific roles in these processes. As we have found that Lyn, but
      not Fyn, activity promotes migration of glioblastoma cells in response to the
      cooperative signal generated by platelet-derived growth factor receptor beta and
      integrin alpha(v)beta3, we compared the activity and expression of Lyn and Fyn in
      glioblastoma (grade IV) tumor biopsy samples with that in anaplastic astrocytoma
      (grade III) tumors, nonneoplastic brain, and normal autopsy brain samples. Lyn
      kinase activity was significantly elevated in glioblastoma tumor samples.
      Notably, the Lyn kinase activity accounted for >90% of pan-Src kinase activity in
      glioblastoma samples but only approximately 30% of pan-Src kinase activity in the
      other groups. The levels of phosphorylation of the autophosphorylation site were
      consistent with significantly higher Lyn activity in glioblastoma tumor tissue
      than nonneoplastic brain. Although the normalized levels of Lyn protein and the
      relative levels of Lyn message were significantly higher in glioblastoma samples
      than nonneoplastic brain, the normalized levels of Lyn protein did not correlate
      with Lyn activity in the glioblastoma samples. There was no significant
      difference in the normalized levels of c-Src and Fyn protein and message in the
      glioblastoma and nonneoplastic brain. Immunostaining revealed that Lyn is located
      primarily in the glioblastoma cells in the tumor biopsies. These data indicate
      that Lyn kinase activity is significantly elevated in glioblastoma tumors and
      suggest that it is the Lyn activity that promotes the malignant phenotype in
      these tumors.

PMID- 15994926
TI  - NBS1 knockdown by small interfering RNA increases ionizing radiation mutagenesis
      and telomere association in human cells.
AB  - Hypomorphic mutations which lead to decreased function of the NBS1 gene are
      responsible for Nijmegen breakage syndrome, a rare autosomal recessive hereditary
      disorder that imparts an increased predisposition to development of malignancy.
      The NBS1 protein is a component of the MRE11/RAD50/NBS1 complex that plays a
      critical role in cellular responses to DNA damage and the maintenance of
      chromosomal integrity. Using small interfering RNA transfection, we have knocked
      down NBS1 protein levels and analyzed relevant phenotypes in two closely related
      human lymphoblastoid cell lines with different p53 status, namely wild-type TK6
      and mutated WTK1. Both TK6 and WTK1 cells showed an increased level of ionizing
      radiation-induced mutation at the TK and HPRT loci, impaired phosphorylation of
      H2AX (gamma-H2AX), and impaired activation of the cell cycle checkpoint
      regulating kinase, Chk2. In TK6 cells, ionizing radiation-induced accumulation of
      p53/p21 and apoptosis were reduced. There was a differential response to ionizing
      radiation-induced cell killing between TK6 and WTK1 cells after NBS1 knockdown;
      TK6 cells were more resistant to killing, whereas WTK1 cells were more sensitive.
      NBS1 deficiency also resulted in a significant increase in telomere association
      that was independent of radiation exposure and p53 status. Our results provide
      the first experimental evidence that NBS1 deficiency in human cells leads to
      hypermutability and telomere associations, phenotypes that may contribute to the
      cancer predisposition seen among patients with this disease.

PMID- 15994927
TI  - Bcl-2 promotes invasion and lung metastasis by inducing matrix metalloproteinase
      2.
AB  - Bcl-2 is involved in the progression of human malignancies, but the precise role
      and mechanism of Bcl-2 for tumor invasion and metastasis remains unclear. In this
      study, we have investigated the role and mechanism of Bcl-2 on tumor cell
      invasion and metastasis by using Bcl-2 overexpressing non-small cell lung cancer
      cells. Matrix metalloproteinases (MMPs) are important proteins involved in the
      processes of tumor invasion and metastasis. In vitro Matrigel invasion assays
      showed that Bcl-2 overexpression increased tumor cell invasion by 15-fold.
      Moreover, Bcl-2 overexpression enhanced in vivo lung metastasis by 4-fold.
      Consistent with its effect on invasion and metastasis, Bcl-2 overexpression
      induced not only MMP-2 mRNA and its protein expression, but this also activated
      the pro-MMP-2 protein to its active form. To explore the induction mechanism of
      MMP-2 by Bcl-2, we investigated the effects of Bcl-2 overexpression on MMP-2
      transcriptional regulation. Nuclear run-on assays showed a 6-fold increase in the
      transcription rate of MMP-2 mRNA in the Bcl-2 transfectants (H157/Bcl-2) compared
      with that of the H157/vector control cells (H157/C). Overexpression of Bcl-2
      induced the nuclear transcription factor activator protein 1 family, including
      the c-Jun, JunD, c-Fos, FosB, and Fra-1 proteins. Reporter assays combined with
      deletion mutagenesis analysis and gel shift assays showed the involvement of
      activator protein 1 in the activation of MMP-2 promoter activity by Bcl-2. Taken
      together, we have shown that Bcl-2 promotes tumor invasion and lung metastasis by
      inducing MMP-2 gene expression through the combined action of transcriptional and
      posttranslational mechanisms.

PMID- 15994928
TI  - Homozygous deletions and chromosome amplifications in human lung carcinomas
      revealed by single nucleotide polymorphism array analysis.
AB  - Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma
      specimens and 31 cell lines derived from human lung carcinomas, with high-density
      arrays representing approximately 115,000 single nucleotide polymorphism loci. In
      addition to previously characterized loci, two regions of homozygous deletion
      were found, one near the PTPRD locus on chromosome segment 9p23 in four samples
      representing both small cell lung carcinoma (SCLC) and non-small cell lung
      carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of
      NSCLC and SCLC. High-level amplifications were identified within chromosome
      segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in
      four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes
      identified high-level amplification of EGFR in three NSCLC specimens, FGFR1 in
      two specimens and ERBB2 and MET in one specimen each. EGFR amplification was
      shown to be independent of kinase domain mutational status.

PMID- 15994929
TI  - Proline-, glutamic acid-, and leucine-rich protein-1 is essential in growth
      factor regulation of signal transducers and activators of transcription 3
      activation.
AB  - Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1) is a novel estrogen
      receptor coactivator that plays an important role in the genomic and nongenomic
      actions of estrogen receptor by interacting with histones and src-mitogen
      activated protein kinase pathway, respectively. A great deal of information has
      emerged in recent years about the possible role of PELP1 in estrogen receptor
      signaling. However, the participation and significance of PELP1 in other cellular
      signaling pathways remains unknown. Using a yeast two-hybrid screen, we
      identified PELP1 as a novel interacting protein of signal transducers and
      activators of transcription 3 (STAT3) and found evidence of physiologic
      interaction between PELP1 and STAT3. We also found that these interactions played
      a mechanistic role in the positive regulation of STAT3 transcription from
      synthetic promoters and endogenous target genes such as cyclin D1, c-myc, and c
      fos. Overexpression of PELP1 enhanced phosphorylation of STAT3 at Ser727 in a src
      mitogen-activated protein kinase-sensitive manner and, conversely, down
      regulation of PELP1 compromised growth factor-mediated induction of STAT3 target
      genes. We also discovered that PELP1 interacts with STAT3 in the nuclear
      compartment and down-regulation of PELP1 interfered with the recruitment of STAT3
      to its target gene promoters. In summary, our results highlight a novel role for
      PELP1 in growth factor signaling and indicate that PELP1-mediated genomic and
      nongenomic functions play a role in the growth factor-mediated STAT3
      transactivation functions. Such regulatory interactions of PELP1 may have
      important functional implications in the cross-talk of estrogen receptor and
      growth factor signaling.

PMID- 15994930
TI  - Using a xenograft model of human breast cancer metastasis to find genes
      associated with clinically aggressive disease.
AB  - Metastasis is the primary cause of death from breast cancer. A xenograft model
      was used to identify genes potentially involved with metastasis, comparing
      expression in the poorly metastatic GI101A human breast cancer cell line and a
      highly metastatic variant, GILM2. cDNA microarray analyses of these isogenic
      variants were done using 16K Operon 70-mer oligonucleotide microarray slides.
      Differentially expressed genes were identified by ANOVA, and differences of > or
      =2.5-fold were found for 106 genes. Changes in protein or RNA expression were
      confirmed for 10 of 12 genes. Three markers, heat shock protein 70 (HSP-70),
      chemokine (C-X-C motif) ligand 1 (CXCL-1), and secreted leukocyte protease
      inhibitor (SLPI), were studied further with breast cancer tissue microarrays
      using a novel method of automated quantitative analysis. This uses cytokeratin to
      define pixels as breast cancer (tumor mask) within the tissue array spot and then
      measures intensity of marker expression using a cyanine 5-conjugated antibody
      within the mask. Scores were correlated with clinicopathologic variables. High
      HSP-70 expression and high nuclear CXCL-1 expression in primary tumors were both
      associated with decreased survival (P = 0.05 and 0.027, respectively). Expression
      of each marker was strongly associated with lymph node involvement (P = 0.0002,
      0.008, 0.0012, and 0.012 for HSP-70, nuclear CXCL-1, cytoplasmic CXCL-1, and
      SLPI, respectively). Identification of genes associated with metastasis in
      experimental models may have clinical implications for the management of breast
      cancer, because some of these are associated with lymph node metastasis and
      survival and might be useful as prognostic markers or molecular targets for novel
      therapies.

PMID- 15994931
TI  - Differentiation of human embryonal carcinomas in vitro and in vivo reveals
      expression profiles relevant to normal development.
AB  - Embryonal carcinoma is a histologic subgroup of testicular germ cell tumors
      (TGCTs), and its cells may follow differentiation lineages in a manner similar to
      early embryogenesis. To acquire new knowledge about the transcriptional programs
      operating in this tumor development model, we used 22k oligo DNA microarrays to
      analyze normal and neoplastic tissue samples from human testis. Additionally,
      retinoic acid-induced in vitro differentiation was studied in relevant cell
      lines. We identified genes characterizing each of the known histologic subtypes,
      adding up to a total set of 687 differentially expressed genes. Among these,
      there was a significant overrepresentation of gene categories, such as genomic
      imprinting and gene transcripts associated to embryonic stem cells. Selection for
      genes highly expressed in the undifferentiated embryonal carcinomas resulted in
      the identification of 58 genes, including pluripotency markers, such as the
      homeobox genes NANOG and POU5F1 (OCT3/4), as well as GAL, DPPA4, and NALP7.
      Interestingly, abundant expression of several of the pluripotency genes was also
      detected in precursor lesions and seminomas. By use of tissue microarrays
      containing 510 clinical testicular samples, GAL and POU5F1 were up-regulated in
      TGCT also at the protein level and hence validated as diagnostic markers for
      undifferentiated tumor cells. The present study shows the unique gene expression
      profiles of each histologic subtype of TGCT from which we have identified
      deregulated components in selected processes operating in normal development,
      such as WNT signaling and DNA methylation.

PMID- 15994932
TI  - Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A
      translation factor detected in breast cancer tissue.
AB  - The ubiquitin (Ub)/proteasome pathway facilitates the degradation of damaged
      proteins and regulators of growth and stress response. The activation of this
      pathway in various cancers and malignancies has been described, and several
      genetic determinants of breast cancer, including BRCA1 and BRCA2, are linked to
      protein degradation. To investigate the involvement of the Ub/proteasome system
      in breast cancer, we examined a collection of 25 patient-matched breast cancer
      and normal adjacent tissues and detected activation of numerous components of the
      Ub/proteasome pathway. The activity of the proteasome, and levels of proteasome
      subunits and various targeting factors, were increased in >90% of primary breast
      cancer tissue specimens. In contrast, no activation was observed in benign solid
      tumors, indicating that the response is specific to abnormal growth in neoplastic
      cells. Additionally, the accumulation of high levels of certain Ub-conjugating
      enzymes (UbcH1, UbcH2, and UbcH5), was specific to breast cancer, as no change in
      abundance was detected in primary colon cancer tissue extracts. Surprisingly, the
      Ub/proteasome system was not activated in a well-characterized cell culture-based
      breast cancer model system. Collectively, these findings suggest that the
      analysis of primary breast cancer tissue samples will be indispensable for the
      biochemical characterization of neoplastic growth and for the development of
      therapeutics.

PMID- 15994933
TI  - Identification of a novel c-Myc protein interactor, JPO2, with transforming
      activity in medulloblastoma cells.
AB  - c-myc oncogene activation is critical in the pathogenesis of a spectrum of human
      malignancies. The c-Myc NH2-terminal domain (MycNTD) is essential for cellular
      transformation, and mediates critical protein interactions that modulate c-Myc
      oncogenic properties. In medulloblastoma, the most common malignant pediatric
      brain tumor, deregulated c-myc expression is linked with poorer disease
      phenotypes and outcomes. The biological basis for these associations is, however,
      not well understood. To better understand mechanisms underlying Myc-mediated
      transformation of medulloblastoma, we sought to identify novel MycNTD protein
      interactors from a medulloblastoma cell line library using a unique two-hybrid
      system. We identified a novel MycNTD binding protein, JPO2, which shows nuclear
      colocalization with c-Myc, and interacts with c-Myc both in vitro and in
      mammalian cells. In Rat1a transformation assays, JPO2 potentiates c-Myc
      transforming activity, and can complement a transformation-defective Myc mutant.
      Immunohistochemical studies indicate tumor-specific JPO2 expression in human
      medulloblastoma, and an association of JPO2 expression with metastatic tumors.
      Significantly, JPO2 expression induces colony formation in UW228, a
      medulloblastoma cell line, whereas RNAi-mediated JPO2 knockdown impairs colony
      formation in UW228, and in Myc-transformed UW228 cells. These data provide
      evidence for biochemical and functional interaction between c-Myc and JPO2 in
      medulloblastoma transformation. JPO2 is closely related to JPO1, a Myc
      transcriptional target with transforming activity. As tumor-specific JPO1
      expression in human and murine medulloblastoma has also been reported; these
      collective observations suggest important functional links between the novel JPO
      protein family and c-Myc in medulloblastoma transformation.

PMID- 15994934
TI  - The Myc target gene JPO1/CDCA7 is frequently overexpressed in human tumors and
      has limited transforming activity in vivo.
AB  - MYC is frequently overexpressed in human cancers, but the downstream events
      contributing to tumorigenesis remain incompletely understood. MYC encodes an
      oncogenic transcription factor, of which target genes presumably contribute to
      cellular transformation. Although Myc regulates about 15% of genes and
      combinations of target genes are likely required for tumorigenesis, we studied in
      depth the expression of the Myc target gene, JPO1/CDCA7, in human cancers and its
      ability to provoke tumorigenesis in transgenic mice. JPO1/CDCA7 is frequently
      overexpressed in human cancers, and in particular, its expression is highly
      elevated in chronic myelogenous leukemia blast crisis as compared with the
      chronic phase. In murine lymphoid tissues, ectopic human JPO1/CDCA7 expression
      resulted in a 2-fold increased risk of lymphoid malignancies at 1 year. The
      transgene, which was driven by the H2-K promoter, exhibited leaky expression in
      nonlymphoid tissues such as kidney. We observed a significant increased incidence
      of transgenic animal solid tumors, which were not seen in littermate controls.
      These observations suggest that JPO1/CDCA7 may contribute to Myc-mediated
      tumorigenesis.

PMID- 15994935
TI  - A molecular classification of papillary renal cell carcinoma.
AB  - Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is
      a disproportionately limited understanding of its underlying genetic programs.
      There is no effective therapy for metastatic PRCC, and patients are often
      excluded from kidney cancer trials. A morphologic classification of PRCC into
      type 1 and 2 tumors has been recently proposed, but its biological relevance
      remains uncertain. We studied the gene expression profiles of 34 cases of PRCC
      using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both
      unsupervised and supervised analyses. Comparative genomic microarray analysis was
      used to infer cytogenetic aberrations, and pathways were ranked with a curated
      database. Expression of selected genes was validated by immunohistochemistry in
      34 samples with 15 independent tumors. We identified two highly distinct
      molecular PRCC subclasses with morphologic correlation. The first class, with
      excellent survival, corresponded to three histologic subtypes: type 1, low-grade
      type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor
      survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1
      S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively,
      alongside characteristic chromosomal aberrations. We identified a seven
      transcript predictor that classified samples on cross-validation with 97%
      accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in
      class 1 tumors and of topoisomerase IIalpha in class 2 tumors. We report two
      molecular subclasses of PRCC, which are biologically and clinically distinct and
      may be readily distinguished in a clinical setting.

PMID- 15994936
TI  - A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis.
AB  - An increased level of dihydrouridine in tRNA(Phe) was found in human malignant
      tissues nearly three decades ago, but its biological significance in
      carcinogenesis has remained unclear. Through analysis of genome-wide gene
      expression profiles among non-small cell lung carcinomas (NSCLC), we identified
      overexpression of a novel human gene, termed hDUS2, encoding a protein that
      shared structural features with tRNA-dihydrouridine synthases (DUS). The deduced
      493-amino-acid sequence showed 39% homology to the dihydrouridine synthase 2
      enzyme (Dus2) of Saccharomyces cerevisiae and contained a conserved double-strand
      RNA-binding motif (DSRM). We found that hDUS2 protein had tRNA-DUS activity and
      that it physically interacted with EPRS, a glutamyl-prolyl tRNA synthetase, and
      was likely to enhance translational efficiencies. A small interfering RNA against
      hDUS2 transfected into NSCLC cells suppressed expression of the gene, reduced the
      amount of dihydrouridine in tRNA molecules, and suppressed growth.
      Immunohistochemical analysis showed significant association between higher levels
      of hDUS2 in tumors and poorer prognosis of lung cancer patients. Our data imply
      that up-regulation of hDUS2 is a relatively common feature of pulmonary
      carcinogenesis and that selective suppression of hDUS2 enzyme activity and/or
      inhibition of formation of the hDUS2-tRNA synthetase complex could be a promising
      therapeutic strategy for treatment of many lung cancers.

PMID- 15994937
TI  - Choline kinase is a novel oncogene that potentiates RhoA-induced carcinogenesis.
AB  - Choline kinase is overexpressed in human breast, lung, colorectal, and prostate
      tumors, a finding that suggests the involvement of this enzyme in carcinogenesis.
      Here we show that overexpression of choline kinase induce oncogenic
      transformation of human embryo kidney fibroblasts and canine epithelial Madin
      Darby canine kidney cells. Choline kinase lays downstream of RhoA signaling and
      is activated through ROCK kinase, one of the best-characterized RhoA effectors.
      In keeping with this, coexpression of RhoA and choline kinase potentiates both
      anchorage independent growth and tumorigenesis. Finally, choline kinase-mediated
      transformation is sensitive to MN58b, a well-characterized specific choline
      kinase inhibitor. These results provide the definitive evidence that choline
      kinase has oncogenic properties and that choline kinase inhibition constitutes a
      novel valid antitumor strategy.

PMID- 15994938
TI  - Distinct B-cell and T-cell lymphoproliferative disease prevalence among dog
      breeds indicates heritable risk.
AB  - Immunophenotypes in lymphoproliferative diseases (LPD) are prognostically
      significant, yet causative factors for these conditions, and specifically those
      associated with heritable risk, remain elusive. The full spectrum of LPD seen in
      humans occurs in dogs, but the incidence and lifetime risk of naturally occurring
      LPD differs among dog breeds. Taking advantage of the limited genetic
      heterogeneity that exists within dog breeds, we tested the hypothesis that the
      prevalence of LPD immunophenotypes would differ among different breeds. The
      sample population included 1,263 dogs representing 87 breeds. Immunophenotype was
      determined by the presence of clonal rearrangements of immunoglobulin heavy chain
      or T-cell receptor gamma chain. The probability of observing the number of B-cell
      or T-cell tumors in a particular breed or breed group was compared with three
      reference populations. Significance was computed using chi2 test, and logistic
      regression was used to confirm binomial predictions. The data show that, among 87
      breeds tested, 15 showed significant differences from the prevalence of LPD
      immunophenotypes seen across the dog population as a whole. More significantly,
      elevated risk for T-cell LPD seems to have arisen ancestrally and is retained in
      related breed groups, whereas increased risk for B-cell disease may stem from
      different risk factors, or combinations of risk factors, arising during the
      process of breed derivation and selection. The data show that domestic dogs
      provide a unique and valuable resource to define factors that mediate risk as
      well as genes involved in the initiation of B-cell and T-cell LPD.

PMID- 15994939
TI  - Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer
      binding protein homologous protein.
AB  - Combined treatment with a proteasome inhibitor and tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) is a promising strategy for cancer therapy.
      Proteasome inhibitors induce the expression of death receptor 5 (DR5), a receptor
      for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the
      molecular mechanism of DR5 up-regulation has not been elucidated. In this study,
      we report that CCAAT/enhancer-binding protein homologous protein (CHOP) is a
      regulator of DR5 induction by proteasome inhibitor MG132. MG132 induced DR5
      expression at a protein and mRNA level in prostate cancer DU145 cells.
      Furthermore, MG132 increased DR5 promoter activity. Using a series of deletion
      mutant plasmids containing DR5 promoters of various sizes, we found that MG132
      stimulated the promoter activity via the region of -289 to -253. This region
      contained a CHOP-binding site. Site-directed mutation of the site abrogated the
      promoter activity enhanced by MG132. An electrophoretic mobility shift assay
      showed that CHOP directly bound to the MG132-responsive site on the DR5 promoter.
      Expression of the CHOP protein was increased with MG132 along with DR5 up
      regulation. Furthermore, CHOP small interfering RNA attenuated the DR5 up
      regulation due to MG132. These results indicate that the proteasome inhibitor
      MG132 induces DR5 expression through CHOP up-regulation.

PMID- 15994940
TI  - Chromosomal instability in unirradiated hemopoietic cells resulting from a
      delayed in vivo bystander effect of gamma radiation.
AB  - Untargeted effects of ionizing radiation (de novo effects in the unirradiated
      descendants or neighbors of irradiated cells) challenge widely held views about
      the mechanisms of radiation-induced DNA damage with implications for the health
      consequences of radiation exposures particularly in the context of the induction
      of malignancy. To investigate in vivo untargeted effects of sparsely ionizing
      (low linear energy transfer) radiation, a congenic sex-mismatch bone marrow
      transplantation protocol has been used to repopulate the hemopoietic system from
      a mixture of gamma-irradiated and nonirradiated hemopoietic stem cells such that
      host-, irradiated donor- and unirradiated donor-derived cells can be
      distinguished. Chromosomal instability in the progeny of irradiated hemopoietic
      stem cells accompanied by a reduction in their contribution to the repopulated
      hemopoietic system is consistent with a delayed genomic instability phenotype
      being expressed in vivo. However, chromosomal instability was also shown in the
      progeny of the nonirradiated hemopoietic stem cells implicating a bystander
      mechanism. Studies of the influence of irradiated recipient stromal
      microenvironment and experiments replacing irradiated cells with irradiated cell
      conditioned medium reveal the source of the in vivo bystander effect to be the
      descendants of irradiated cells, rather than irradiated cell themselves. Thus, it
      is possible that a radiation-induced genomic instability phenotype in vivo need
      not necessarily be a reflection of intrinsically unstable cells but the responses
      to ongoing production of inflammatory-type damaging signals as a long-term
      unexpected consequence of the initial single radiation exposure.

PMID- 15994941
TI  - Lack of telopeptides in fibrillar collagen I promotes the invasion of a
      metastatic breast tumor cell line.
AB  - Defective fibrillar collagen polymerization in primary tumors has been correlated
      with increased metastasis. However, it is unclear how collagen organization
      influences tumor invasion. In this study, we show that collagen I polymerized
      without telopeptides (the flanking regions of collagen molecules) can
      differentially affect the three-dimensional migration of mammary carcinoma cells.
      MDA-MB-231 cells capable of proteolytic degradation and mesenchymal motion,
      invaded telopeptide-intact and telopeptide-free collagen gels to the same extent.
      In contrast, MDA-MB-435S cells, with typical features of amoeboid cells (poor
      collagenolytic activity, rounded cell morphology), were 5-fold more invasive in
      telopeptide-free than telopeptide-intact collagen. A fraction of the MDA-MB-435S
      cells that invaded telopeptide-intact or telopeptide-free collagen had a rounded
      morphology; however, in telopeptide-free collagen, a significant fraction of the
      cells switched from a rounded to elongated morphology (protrusion formation). The
      dynamic changes in cellular shape facilitated MDA-MB-435S locomotion through the
      narrow interfiber gaps, which were smaller than cell diameters. Based on the
      spherical morphology of MDA-MB-435S cells, we tested if the changes in cell shape
      and invasion were related to RhoA-ROCK activity; GTP-bound RhoA was measured in
      pull-down assays. RhoA activity was 1.8-fold higher for MDA-MB-435S cells seeded
      on telopeptide-free than telopeptide-intact collagen. Y27632 inhibition of ROCK,
      a Rho effector, significantly reduced the changes in cellular morphodynamics and
      the invasion of MDA-MB-435S cells but did not alter the invasion of MDA-MB-231
      cells. Thus, the higher RhoA activity of MDA-MB-435S cells in telopeptide-free
      collagen enhances the changes in cellular morphodynamics associated with motility
      and invasion.

PMID- 15994942
TI  - A novel role for extracellular signal-regulated kinase 5 and myocyte enhancer
      factor 2 in medulloblastoma cell death.
AB  - Expression of the neurotrophin-3 receptor, tyrosine kinase C (TrkC), is
      associated with favorable prognosis in medulloblastoma patients. This may be due
      to increased tumor apoptosis induced by TrkC activation. Neurotrophin-3/TrkC
      induced apoptosis is inhibited by the mitogen-activated protein (MAP) kinase
      (MAPK) pharmacologic antagonists SB203580 and PD98059. In addition to
      extracellular signal-regulated kinase (ERK)-1/2, PD98059 also inhibits the more
      recently identified neurotrophin-responsive MAPK, ERK5 (big MAPK 1). In the
      present study, we investigate the contribution of ERK5 and its target myocyte
      enhancer factor 2 (MEF2) to neurotrophin-3/TrkC-induced medulloblastoma cell
      death. Neurotrophin-3 not only enhanced ERK5 phosphorylation but also
      significantly enhanced the transcriptional activity of MEF2, a specific target of
      ERK5. Overexpression of both ERK5 and MEF2 induced a statistically significant
      increase in cell death of neurotrophin-3-responsive and nonresponsive
      medulloblastoma cell lines (Daoy-trkC and Daoy) and primary cultures of patched
      heterozygous mouse medulloblastomas. Only those cells expressing MAP/ERK kinase 5
      (MEK5) plus ERK5 or MEF2 constructs underwent apoptosis, indicating that
      overexpression of either is sufficient to induce medulloblastoma cell death.
      Expression of a dominant-negative MEF2 or small interfering RNA for the ERK5
      activator, MEK5, significantly inhibited neurotrophin-3-induced cell death. The
      dominant-negative MEF2 construct also blocked MEK5/ERK5-induced cell death,
      supporting a role for MEF2 downstream of ERK5. Co-immunoprecipitation studies
      revealed direct interaction of phosphorylated ERK5 with MEF2 in response to
      neurotrophin-3. Our investigation of the mechanism of neurotrophin-3/TrkC-induced
      apoptosis has identified a novel role for both MEK5/ERK5 and MEF2 in cell death,
      suggesting that these molecules can be exploited to induce apoptosis in both TrkC
      expressing and non-expressing medulloblastoma cells.

PMID- 15994943
TI  - X-linked dominant growth suppression of transplanted tumors in C57BL/6J-scid
      mice.
AB  - Tumor susceptibility, angiogenesis, and immune response differ between mouse
      strains. We, therefore, examined the growth rates of tumor xenografts in three
      genetically isolated strains of severe combined immunodeficient mice (C.B-17,
      C57BL/6J, and C3H). Tumors grew at significantly reduced rates in the C57BL/6J
      scid strain. Engrafting bone marrow from the C57BL/6J-scid strain onto C.B-17
      scid mice did not transfer the slow-growing tumor phenotype to the recipient
      mice; this counters the supposition that the slow-growing tumor phenotype is
      caused by a greater immune response to the xenograft in the C57BL/6J-scid strain.
      To establish the inheritance pattern of the slow-growing tumor phenotype, we
      reciprocally crossed C.B-17-scid mice and C57BL/6J-scid mice. Tumor growth was
      suppressed in all of the F1 progeny except the male mice derived from the cross
      between C.B-17-scid female and C57BL/6J-scid male mice. The F1 male mice that
      received the X chromosome from the C.B-17 strain displayed a fast-growing tumor
      phenotype. These results confirm that there are significant strain differences in
      capacity to support the growth of tumor xenografts. In addition, these results
      reveal the existence of a dominant allele involved in host suppression of tumor
      growth on the X chromosome of C57BL/6J mice.

PMID- 15994944
TI  - The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival
      pathways in breast cancer.
AB  - S100A7 is among the most highly expressed genes in preinvasive breast cancer, is
      a marker of poor survival when expressed in invasive disease, and promotes breast
      tumor progression in experimental models. To explore the mechanism of action, we
      examined the role of S100A7 in cell survival and found that overexpression of
      S100A7 in MDA-MB-231 cell lines promotes survival under conditions of anchorage
      independent growth. This effect is paralleled by increased activity of nuclear
      factor-kappaB (3-fold) and phospho-Akt (4-fold), which are known to mediate
      prosurvival pathways. S100A7 and phospho-Akt are also correlated in breast tumors
      examined by immunohistochemistry (n = 142; P < 0.0001; r = 0.34). To explore the
      underlying mechanism, we examined the role of a putative c-Jun activation domain
      binding protein 1 (Jab1)-binding domain within S100A7 using a panel of MDA-MB-231
      breast cell lines stably transfected with either S100A7 or S100A7 mutated at the
      Jab1 domain. Structural analysis by three-dimensional protein modeling,
      immunoprecipitation, and yeast two-hybrid assay and functional analysis using
      transfected reporter gene and Western blot assays revealed that the in vitro
      effects of S100A7 on phospho-Akt and the nuclear factor-kappaB pathway are
      dependent on the Jab1-binding site and the interaction with Jab1. Enhanced
      epidermal growth factor receptor signaling was also found to correlate with the
      increased phospho-Akt. Furthermore, the Jab1-binding domain is also necessary for
      the enhanced tumorigenicity conferred by S100A7 expression in murine xenograft
      tumors in vivo. We conclude that the S100A7-Jab1 pathway acts to enhance survival
      under conditions of cellular stress, such as anoikis, which may promote
      progression of breast cancer.

PMID- 15994945
TI  - Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor
      growth.
AB  - The junctional adhesion molecule-C (JAM-C) was recently described as an adhesion
      molecule localized at interendothelial contacts and involved in leukocyte
      transendothelial migration. The protein JAM-C interacts with polarity complex
      molecules and regulates the activity of the small GTPase Cdc42. The angiogenesis
      process involves rearrangement of endothelial junctions and implicates modulation
      of cell polarity. We tested whether JAM-C plays a role in angiogenesis using
      tumor grafts and hypoxia-induced retinal neovascularization. Treatment with a
      monoclonal antibody directed against JAM-C reduces tumor growth and infiltration
      of macrophages into tumors. The antibody decreases angiogenesis in the model of
      hypoxia-induced retinal neovascularization in vivo and vessel outgrowth from
      aortic rings in vitro. Importantly, the antibody does not induce pathologic side
      effects in vivo. These findings show for the first time a role for JAM-C in
      angiogenesis and define JAM-C as a valuable target for antitumor therapies.

PMID- 15994946
TI  - Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor
      beta signaling inhibits human renal cell carcinoma progression in an orthotopic
      mouse model.
AB  - Renal cell carcinoma is a highly malignant and often fatal disease of the kidney.
      It is difficult to treat, often because metastases are common at the time of
      presentation. Platelet-derived growth factor-D (PDGF-D) is a newly discovered
      member of the PDGF family; its function in tumor progression is largely unknown.
      Here, we examined the expression level of PDGF-D in human renal cell carcinoma by
      immunohistochemical staining using tissue arrays. We showed that human renal cell
      carcinoma expresses high levels of PDGF-D protein. The human renal cell carcinoma
      cell line SN12-C was stably transfected with pdgf-d cDNA. Overexpression of PDGF
      D in SN12-C cells promoted tumor growth, angiogenesis, and metastasis of human
      renal cell carcinoma in an orthotopic severe combined immunodeficient (SCID)
      mouse model. PDGF-D overproduction in SN12-C cells increased the proliferation
      and migration of mural cells in vitro and improved perivascular cell coverage in
      vivo. Overexpression of PDGF-D led to increased expression of angiopoietin-1 and
      matrix metalloproteinase-9 in tumor tissues. ShRNAi and Gleevec were used to
      block PDGF-D expression and PDGF receptor beta (PDGFRbeta) signaling. Inhibition
      of PDGF-D expression by short hairpin RNA interference (shRNAi) and blockage of
      PDGFRbeta signaling by Gleevec inhibited the growth and lung metastasis of SN12-C
      cells grown orthotopically in SCID mice. Thus, PDGF-D is a potential candidate
      for controlling the progression of metastatic renal cell carcinoma. This opens up
      an avenue of investigation into novel therapeutic strategies for the treatment of
      renal cell carcinoma, including the use of recently developed tyrosine kinase
      inhibitors, such as Gleevec, which inhibit PDGF activity through inhibition of
      its receptor tyrosine kinase.

PMID- 15994947
TI  - Signal transducer and activator of transcription 3 is a key regulator of
      keratinocyte survival and proliferation following UV irradiation.
AB  - UVB irradiation of signal transducer and activator of transcription 3 (Stat3)
      deficient keratinocytes resulted in a high incidence of apoptosis compared with
      controls. Conversely, forced expression of Stat3 desensitized keratinocytes to
      UVB-induced apoptosis. Upon UVB exposure, keratinocyte Stat3 was rapidly
      dephosphorylated, followed by decreases of both Stat3 mRNA and protein levels in
      a p53-independent manner. Vanadate treatment reversed the UVB-induced down
      regulation of Stat3 and generation of apoptotic keratinocytes, suggesting the
      involvement of a tyrosine phosphatase. Furthermore, Stat3 was required for UVB
      induced proliferation of follicular keratinocytes, leading to epidermal
      thickening. Finally, constitutive activation of Stat3 was observed in UVB-induced
      squamous cell carcinomas of either mice or human origin. These data suggest that
      Stat3 is required for survival and proliferation of keratinocytes following UVB
      exposure and that Stat3 is tightly regulated as part of a novel protective
      mechanism against UVB-induced skin cancer.

PMID- 15994948
TI  - Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate
      cancer accompanied by increased epithelial cell proliferation but not by reduced
      apoptosis.
AB  - The PTEN tumor suppressor gene is frequently inactivated in human tumors,
      including prostate cancer. Based on the Cre/loxP system, we generated a novel
      mouse prostate cancer model by targeted inactivation of the Pten gene. In this
      model, Cre recombinase was expressed under the control of the prostate-specific
      antigen (PSA) promoter. Conditional biallelic and monoallelic Pten knock-out mice
      were viable and Pten recombination was prostate-specific. Mouse cohorts were
      systematically characterized at 4 to 5, 7 to 9, and 10 to 14 months. A slightly
      increased proliferation rate of epithelial cells was observed in all prostate
      lobes of monoallelic Pten knock-out mice (PSA-Cre;Pten-loxP/+), but minimal
      pathologic changes were detected. All homozygous knock-out mice (PSA-Cre;Pten
      loxP/loxP) showed an increased size of the luminal epithelial cells, large areas
      of hyperplasia, focal prostate intraepithelial neoplasia lesions and an increased
      prostate weight at 4 to 5 months. More extensive prostate intraepithelial
      neoplasia and focal microinvasion occurred at 7 to 9 months; invasive prostate
      carcinoma was detected in all male PSA-Cre;Pten-loxP/loxP mice at 10 to 14
      months. At 15 to 16 months, a rare lymph node metastasis was found. In
      hyperplastic cells and in tumor cells, the expression of phospho-AKT was up
      regulated. In hyperplastic and tumor cells, expression of luminal epithelial cell
      cytokeratins was up-regulated; tumor cells were negative for basal epithelial
      cell cytokeratins. Androgen receptor expression remained detectable at all stages
      of tumor development. The up-regulation of phospho-AKT correlated with an
      increased proliferation rate of the epithelial cells, but not with a reduced
      apoptosis.

PMID- 15994949
TI  - Mosaic tumor vessels: cellular basis and ultrastructure of focal regions lacking
      endothelial cell markers.
AB  - Endothelial cells of blood vessels in tumors may be thin, fragile, and defective
      in barrier function. We found previously that the endothelium of vessels in human
      colon carcinoma xenografts in mice is a mosaic structure. Approximately 85% of
      tumor vessels have uniform CD31 and/or CD105 immunoreactivity, but the remainder
      have focal regions that lack these common endothelial markers. The present study
      assessed the ultrastructure of the vessel lining and the integrity of the
      basement membrane in these regions. Using immunolabeling and confocal microscopy,
      we identified blood vessels that lacked CD31 and CD105 immunoreactivity and then
      analyzed the ultrastructure of these vessels by transmission electron microscopy.
      Eleven percent of vessels in orthotopic tumors and 24% of vessels in ectopic
      tumors had defects in CD31 and CD105 staining measuring on average 10.8 microm
      (range, 1-41.2 microm). Ultrastructural studies identified endothelial cells at
      92% of CD31- and CD105-negative sites in orthotopic tumors and 70% of the sites
      in ectopic tumors. Thus, most regions of tumor vessels that lack CD31 and CD105
      immunoreactivity represent attenuated endothelial cells with abnormal expression
      of endothelial cell markers, but some are gaps between endothelial cells. More
      than 80% of the defects lacked immunoreactivity for multiple basement membrane
      proteins.

PMID- 15994950
TI  - Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1
      and E-selectin ligand-1, on human metastatic prostate tumor cells.
AB  - Prostate tumor cells, which characteristically metastasize to bone, initiate
      binding interactions with bone marrow endothelium under blood flow conditions
      through binding interactions with E-selectin. We hypothesized that E-selectin
      ligands on prostate tumor cells are directly associated with bone-metastatic
      potential. In this report, we elucidate the identity of E-selectin ligands on
      human metastatic prostate tumor cells and examine their association with prostate
      tumor progression and metastasis in vivo. To our surprise, we found that the E
      selectin-binding form of P-selectin glycoprotein ligand-1 (PSGL-1) is expressed
      on the human bone-metastatic prostate tumor MDA PCa 2b cell line. Interestingly,
      we also found that human prostate tumor cells derived from bone, lymph node, and
      brain metastases expressed another leukocyte E-selectin ligand, E-selectin ligand
      1 (ESL-1). Immunohistochemical analysis of PSGL-1 and ESL-1 in normal prostate
      tissue and in localized and metastatic prostate tumors revealed that ESL-1 was
      principally localized to intracellular cell membrane and expressed on all normal
      and malignant prostate tissue, whereas PSGL-1 was notably detected on the
      surfaces of bone-metastatic prostate tumor cells. These findings implicate a
      functional role of PSGL-1 in the bone tropism of prostate tumor cells and
      establish a new perspective into the molecular mechanism of human prostate tumor
      metastasis.

PMID- 15994951
TI  - Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate
      cancer cell growth and spread.
AB  - Prostate cancer is a leading cause of cancer death in men. Risk prognostication,
      treatment stratification, and the development of rational therapeutic strategies
      lag because the molecular mechanisms underlying the initiation and progression
      from primary to metastatic disease are unknown. Multiple lines of evidence now
      suggest that KLF6 is a key prostate cancer tumor suppressor gene including loss
      and/or mutation in prostate cancer tumors and cell lines and decreased KLF6
      expression levels in recurrent prostate cancer samples. Most recently, we
      identified a common KLF6 germ line single nucleotide polymorphism that is
      associated with an increased relative risk of prostate cancer and the increased
      production of three alternatively spliced, dominant-negative KLF6 isoforms. Here
      we show that although wild-type KLF6 (wtKLF6) acts as a classic tumor suppressor,
      the single nucleotide polymorphism-increased splice isoform, KLF6 SV1, displays a
      markedly opposite effect on cell proliferation, colony formation, and invasion.
      In addition, whereas wtKLF6 knockdown increases tumor growth in nude mice >2
      fold, short interfering RNA-mediated KLF6 SV1 inhibition reduces growth by
      approximately 50% and decreases the expression of a number of growth- and
      angiogenesis-related proteins. Together, these findings begin to highlight a
      dynamic and functional antagonism between wtKLF6 and its splice variant KLF6 SV1
      in tumor growth and dissemination.

PMID- 15994952
TI  - Diverse biological effect and Smad signaling of bone morphogenetic protein 7 in
      prostate tumor cells.
AB  - We found that bone morphogenetic protein (BMP) 7, a member of the BMP family, was
      strikingly up-regulated during the development of primary prostatic
      adenocarcinoma in the conditional Pten deletion mouse model. To determine the
      relevance of this finding to human prostate cancer, we examined the expression of
      BMPs and BMP receptors (BMPR) as well as the responsiveness to recombinant human
      BMP7 in a series of human prostate tumor cell lines. All prostatic cell lines
      tested expressed variable levels of BMP2, BMP4, and BMP7 and at least two of each
      type I and II BMPRs. In all cases, BMP7 induced Smad phosphorylation in a dose
      dependent manner, with Smad5 activation clearly demonstrable. However, the
      biological responses to BMP7 were cell type specific. BPH-1, a cell line
      representing benign prostatic epithelial hyperplasia, was growth arrested at G1.
      In the bone metastasis-derived PC-3 prostate cancer cells, BMP7 induced
      epithelial-mesenchymal transdifferentiation with classic changes in morphology,
      motility, invasiveness, and molecular markers. Finally, BMP7 inhibited serum
      starvation-induced apoptosis in the LNCaP prostate cancer cell line and more
      remarkably in its bone metastatic variant C4-2B line. Each of the cell lines
      influenced by BMP7 was also responsive to BMP2 in a corresponding manner. The
      antiapoptotic activity of BMP7 in the LNCaP and C4-2B cell lines was not
      associated with a significant alteration in the levels of the proapoptotic
      protein Bax or the antiapoptotic proteins Bcl-2, Bcl-xl, and X-linked inhibitor
      of apoptosis. However, in C4-2B cells but not in LNCaP cells, a starvation
      induced decrease in the level of survivin was counteracted by BMP7. Taken
      together, these findings suggest that BMPs are able to modulate the biological
      behavior of prostate tumor cells in diverse and cell type-specific manner and
      point to certain mechanisms by which these secreted signaling molecules may
      contribute to prostate cancer growth and metastasis.

PMID- 15994953
TI  - Expression of heparanase by primary breast tumors promotes bone resorption in the
      absence of detectable bone metastases.
AB  - Heparanase is an enzyme that cleaves heparan sulfate and through this activity
      promotes tumor growth, angiogenesis, invasion, and metastasis in several tumor
      types. In human breast cancer patients, heparanase expression is associated with
      sentinel lymph node metastases. However, the precise role of heparanase in the
      malignant progression of breast cancer is unknown. To examine this, a variant of
      MDA-MB-231 cells was transfected with the cDNA for human heparanase (HPSE cells)
      or with vector alone as a control (NEO cells). Transfection produced a 6-fold
      increase in heparanase activity in HPSE cells relative to NEO cells. When
      injected into the mammary fat pads of severe combined immunodeficient mice, the
      tumors formed by HPSE cells initially grow significantly faster than the tumors
      formed by NEO cells. The rapid growth is due in part to increased angiogenesis,
      as microvessel densities are substantially elevated in primary HPSE tumors
      compared with NEO tumors. Although metastases to bones are not detected,
      surprisingly vigorous bone resorption is stimulated in animals bearing tumors
      formed by the HPSE cells. These animals have high serum levels of the C
      telopeptide derived from type I collagen as well as significant elevation of the
      active form of tartrate-resistant acid phosphatase (TRAP)-5b. In contrast, in
      animals having a high tumor burden of Neo cells, the serum levels of C
      telopeptide and TRAP-5b never increase above the levels found before tumor
      injection. Consistent with these findings, histologic analysis for TRAP
      expressing cells reveals extensive osteoclastogenesis in animals harboring HPSE
      tumors. In vitro osteoclastogenesis assays show that the osteoclastogenic
      activity of HPSE cell conditioned medium is significantly enhanced beyond that of
      NEO conditioned medium. This confirms that a soluble factor or factors that
      stimulate osteoclastogenesis are specifically produced when heparanase expression
      is elevated. These factors exert a distal effect resulting in resorption of bone
      and the accompanying enrichment of the bone microenvironment with growth
      promoting factors that may nurture the growth of metastatic tumor cells. This
      novel role for heparanase as a promoter of osteolysis before tumor metastasis
      suggests that therapies designed to block heparanase function may disrupt the
      early progression of bone-homing tumors.

PMID- 15994954
TI  - Vascular targeting and antiangiogenesis agents induce drug resistance effector
      GRP78 within the tumor microenvironment.
AB  - Therapeutic targeting of the tumor vasculature that destroys preexisting blood
      vessels of the tumor and antiangiogenesis therapy capitalize on the requirement
      of tumor cells on an intact vascular supply for oxygen and nutrients for growth,
      expansion and metastasis to the distal organs. Whereas these classes of agents
      show promise in delaying tumor progression, they also create glucose and oxygen
      deprivation conditions within the tumor that could trigger unintended prosurvival
      responses. The glucose-regulated protein GRP78, a major endoplasmic reticulum
      chaperone, is inducible by severe glucose depletion, anoxia, and acidosis. Here
      we report that in a xenograft model of human breast cancer, treatment with the
      vascular targeting agent, combretastatin A4P, or the antiangiogenic agent,
      contortrostatin, promotes transcriptional activation of the Grp78 promoter and
      elevation of GRP78 protein in surviving tumor cells. We further show that GRP78
      is overexpressed in a panel of human breast cancer cells that has developed
      resistance to a variety of drug treatment regimens. Suppression of GRP78 through
      the use of lentiviral vector expressing small interfering RNA sensitizes human
      breast cancer cells to etoposide-mediated cell death. Our studies imply that
      antivascular and antiangiogenesis therapy that results in severe glucose and
      oxygen deprivation will induce GRP78 expression that could lead to drug
      resistance.

PMID- 15994955
TI  - Kinase-inactive glycogen synthase kinase 3beta promotes Wnt signaling and mammary
      tumorigenesis.
AB  - Recent studies have implicated ectopic activation of the Wnt pathway in many
      human cancers, including breast cancer. beta-catenin is a critical coactivator in
      this signaling pathway and is regulated in a complex fashion by phosphorylation,
      degradation, and nuclear translocation. Glycogen synthase kinase 3beta (GSK3beta)
      phosphorylation of the NH2-terminal domain of beta-catenin targets it for
      ubiquitination and proteosomal degradation. We hypothesized that expression of
      kinase-inactive GSK3beta (KI-GSK3beta) in mammary glands would function in a
      dominant-negative fashion by antagonizing the endogenous activity of GSK3beta and
      promoting breast cancer development. Consistent with this, we find that KI
      GSK3beta stabilizes beta-catenin expression, catalyzes its localization to the
      nucleus, and up-regulates the downstream target gene, cyclin D1, in vitro. In
      vivo, transgenic mice overexpressing the KI-GSK3beta under the control of the
      mouse mammary tumor virus-long terminal repeat develop mammary tumors with
      overexpression of beta-catenin and cyclin D1. Thus, antagonism of GSK3beta
      activity is oncogenic in the mammary epithelium; mutation or pharmacologic down
      regulation of GSK3beta could promote mammary tumors.

PMID- 15994956
TI  - Selective insensitivity of ZR-75-1 human breast cancer cells to 2
      methoxyestradiol: evidence for type II 17beta-hydroxysteroid dehydrogenase as the
      underlying cause.
AB  - 2-Methoxyestradiol (2-MeO-E2), a nonpolar endogenous metabolite of 17beta
      estradiol, has strong antiproliferative, apoptotic, and antiangiogenic actions.
      Among the four human breast cancer cell lines tested (MCF-7, T-47D, ZR-75-1, and
      MDA-MB-435s), the ZR-75-1 cells were selectively insensitive to the
      antiproliferative actions of 2-MeO-E2, although these cells had a similar
      sensitivity as other cell lines to several other anticancer agents (5
      fluorouracil, mitomycin C, doxorubicin, colchicine, vinorelbine, and paclitaxel).
      Mechanistically, this insensitivity is largely attributable to the presence of
      high levels of a steroid-selective metabolizing enzyme, the type II 17beta
      hydroxysteroid dehydrogenase (17beta-HSD), in the ZR-75-1 cells, which rapidly
      converts 2-MeO-E2 to the inactive 2-methoxyestrone, but this enzyme does not
      metabolically inactivate other nonsteroidal anticancer agents. The type II 17beta
      HSD-mediated conversion of 2-MeO-E2 to 2-methoxyestrone in ZR-75-1 cells followed
      the first-order kinetics, with a very short half-life (approximately 2 hours). In
      comparison, the T-47D, MCF-7, and MDA-MB-435s human breast cancer cells, which
      were highly sensitive to 2-MeO-E2, had very low or undetectable catalytic
      activity for the conversion of 2-MeO-E2 to 2-methoxyestrone. Reverse
      transcription-PCR analysis of the mRNA levels of three known oxidative 17beta-HSD
      isozymes (types II, IV, and VIII) revealed that only the type II isozyme was
      selectively expressed in the ZR-75-1 cells, whereas the other two isozymes were
      expressed in all four cell lines. Taken together, our results showed, for the
      first time, that the high levels of type II 17beta-HSD present in ZR-75-1 cells
      were largely responsible for the facile conversion of 2-MeO-E2 to 2
      methoxyestrone and also for the selective insensitivity to the antiproliferative
      actions of 2-MeO-E2.

PMID- 15994957
TI  - CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity.
AB  - Metastasis of circulating tumor cells requires a multistep cascade of events
      initiated by adhesion of tumor cells to the vascular endothelium of involved
      tissues. This process occurs under the forces of blood flow and is promoted by
      adhesion molecules specialized to interact under shear conditions. The
      endothelial molecule E-selectin is a major mediator of these adhesive events, and
      there is strong evidence that E-selectin receptor-ligand interactions contribute
      to the formation of metastasis. However, little is known about the identity of E
      selectin ligand(s) expressed on cancer cells. To address this issue, we did SDS
      PAGE analysis of membrane proteins, metabolic inhibition studies, and blot
      rolling assays of LS174T, a colon carcinoma cell line known to interact with E
      selectin under physiologic flow conditions. Our studies show that LS174T cells
      express the hematopoietic cell E/L-selectin (HCELL) glycoform of CD44, which
      functions as a high-affinity E-selectin glycoprotein ligand on these cells.
      However, in contrast to the HCELL glycoform on human hematopoietic progenitor
      cells, which expresses carbohydrate-binding determinant(s) for E-selectin
      primarily on N-glycans of standard CD44, the relevant determinant(s) on LS174T
      cells is expressed on O-glycans and is predominantly found on variant isoforms of
      CD44 (CD44v). Our finding that tumor-associated CD44 splice variant(s) express E
      selectin ligand activity provides novel perspectives on the biology of CD44 in
      cancer metastasis.

PMID- 15994959
TI  - Malignant transformation but not normal cell growth depends on signal transducer
      and activator of transcription 3.
AB  - Signal transducer and activator of transcription 3 (STAT3) has been indirectly
      implicated in numerous fundamental cellular processes, including proliferation,
      survival, and differentiation. We provide genetic evidence from studies of STAT3
      null cells that STAT3 is dispensable for normal growth of mouse fibroblasts in
      culture. STAT3 contributed to the full induction of some (typified by c-fos) but
      not all (typified by c-myc) immediate early gene expression, but STAT3
      independent processes were sufficient to support full cell growth and survival.
      However, STAT3 was required to manifest a transformed state following expression
      of v-src, and STAT3-null cells were impaired for anchorage-independent growth as
      colonies in soft agar and as tumors in mice. The data suggest that STAT3 mediates
      the maintenance of focal adhesion kinase activity in the absence of cell adhesion
      by suppressing the action of an inhibitory phosphatase.

PMID- 15994958
TI  - Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell
      transformation.
AB  - Very little is known about the role of histone H3 phosphorylation in malignant
      transformation and cancer development. Here, we examine the function of H3
      phosphorylation in cell transformation in vivo. Introduction of small interfering
      RNA-H3 into JB6 cells resulted in decreased epidermal growth factor (EGF)-induced
      cell transformation. In contrast, wild-type histone H3 (H3 WT)-overexpressing
      cells markedly stimulated EGF-induced cell transformation, whereas the H3 mutant
      S10A cells suppressed transformation. When H3 WT was overexpressed, EGF induction
      of c-fos and c-jun promoter activity was significantly increased compared with
      control cells but not in the H3 mutant S10A or S28A cells. In addition, activator
      protein-1 activity in H3 WT-overexpressing cells was markedly up-regulated by EGF
      in contrast to the H3 mutant S10A or S28A cells. These results indicate that the
      phosphorylation of histone H3 at Ser10 is an essential regulatory mechanism for
      EGF-induced neoplastic cell transformation.

PMID- 15994960
TI  - Major vault protein, in concert with constitutively photomorphogenic 1,
      negatively regulates c-Jun-mediated activator protein 1 transcription in
      mammalian cells.
AB  - Constitutively photomorphogenic 1 (COP1), a RING finger ubiquitin ligase with
      substrates including c-Jun and p53, was recently found to be overexpressed in a
      number of breast and ovarian tumor samples. In addition to its E3 activity, COP1
      was also shown to be able to inhibit activator protein 1 (AP-1) transcription.
      Through an affinity purification method, we have identified major vault protein
      (MVP) as a novel interacting partner for COP1 in mammalian cells. MVP, also known
      as lung resistance protein, is the main component of a ribonucleoprotein
      organelle called vault, and has been implicated in multiple drug resistance in
      many cancer cell lines and primary tumor samples. The interaction between COP1
      and MVP is detectable at the endogenous level and occurs mostly in the cytoplasm.
      Similar to COP1, MVP inhibits c-Jun accumulation and AP-1 transcription activity.
      MVP knockout or knockdown cells contain elevated amount of c-Jun and increased AP
      1 transcription activity. UV irradiation enhances MVP tyrosine phosphorylation,
      causes dissociation of COP1 from MVP, and alleviates the inhibitory activity of
      MVP on AP-1 transcription. Taken together, we propose that MVP, most likely
      through its interaction with COP1, suppresses c-Jun-mediated AP-1 transcription
      under unstressed conditions, thereby preventing cells from undergoing stress
      response.

PMID- 15994961
TI  - Farnesyltransferase inhibitor SCH66336 induces rapid phosphorylation of
      eukaryotic translation elongation factor 2 in head and neck squamous cell
      carcinoma cells.
AB  - Farnesyltransferase inhibitors (FTI) are a class of therapeutic agents designed
      to target tumors with mutations of the ras oncogene. However, the biological
      effect of FTIs is often independent of ras mutation status, which suggests the
      existence of additional mechanisms. In this study, we investigated the molecular
      effects of SCH66336, an FTI, in head and neck squamous cell carcinoma cells using
      proteomic approaches. We showed that SCH66336 induced phosphorylation
      (inactivation) of eukaryotic translation elongation factor 2 (eEF2), an important
      molecule for protein synthesis, as early as 3 hours after SCH66336
      administration. Protein synthesis was subsequently reduced in the cells.
      Paradoxically, activation of eEF2 kinase (eEF2K), the only known kinase that
      regulates eEF2, was observed only at 12 hours after SCH66336 treatment.
      Consistent with this observation, the inhibition of phosphorylated-MEK and
      phosphorylated-p70S6K, the two key signaling molecules responsible for activation
      of eEF2K, also occurred at least 12 hours after SCH66336 administration. Our data
      suggest that inhibition of protein synthesis through inactivation of eEF2 is a
      novel mechanism of SCH66336-mediated growth inhibition and that this effect is
      independent of ras-MEK/p70S6K-eEF2K signaling cascades.

PMID- 15994962
TI  - Synergy of epidermal growth factor receptor kinase inhibitor AG1478 and ErbB2
      kinase inhibitor AG879 in human colon carcinoma cells is associated with
      induction of apoptosis.
AB  - Previous studies have shown that constitutive activation of epidermal growth
      factor receptor (EGFR) and ErbB2 by elevated autocrine transforming growth factor
      alpha (TGF-alpha) expression plays an important role in colon cancer progression.
      Coexpression of EGFR and ErbB2 is found in a subset of colon cancers and may
      cooperatively promote cancer cell growth and survival, as heterodimerization is
      known to provide for diversification of signal transduction. In this study, the
      EGFR-selective tyrosine kinase inhibitor (TKI) AG1478 inhibited cell growth of an
      aggressive human colon carcinoma cell line, FET6alphaS26X, which harbors
      constitutively activated EGFR after stable transfection with TGF-alpha cDNA.
      However, AG1478 failed to induce apoptosis in FET6alphaS26X cells at
      concentrations sufficient for cell growth inhibition and complete suppression of
      EGFR phosphorylation. Similarly, AG879, a selective ErbB2 TKI, was incapable of
      inducing apoptosis in FET6alphaS26X cells at concentrations sufficient to inhibit
      cell growth and ErbB2 phosphorylation. To test the hypothesis that targeting both
      ErbB family members would show better efficacy than targeting the single
      receptors, combinations of inhibitors at fixed ratios of 1:1, 5:1, and 10:1 of
      AG1478 and AG879, respectively, were compared with single drugs for inhibition of
      cell growth. All combinations resulted in synergistic effects as indicated by
      combination index analysis. Synergistic inhibition was associated with induction
      of apoptosis as reflected by poly(ADP-ribose) polymerase cleavage, caspase-3
      activation, and Annexin V staining. Finally, Western blot analysis showed
      significant inhibition of phosphorylation of both EGFR and ErbB2 by the
      combination treatment. These data suggest that the strategy to target both EGFR
      and ErbB2 simultaneously might result in more efficient inhibition of tumor
      growth than to target single receptor alone.

PMID- 15994963
TI  - Human malignant melanomas express receptors for luteinizing hormone releasing
      hormone allowing targeted therapy with cytotoxic luteinizing hormone releasing
      hormone analogue.
AB  - Cytotoxic analogue of luteinizing hormone releasing hormone (LHRH), AN-207, binds
      with high affinity to LHRH receptors and can be targeted to tumors expressing
      these receptors. We investigated the expression of LHRH receptors in surgical
      specimens of human malignant melanoma and evaluated the effects of AN-207 in
      models of human melanoma. Human melanoma specimens derived from primary tumors or
      metastases were examined for LHRH receptor expression by immunohistochemistry.
      Binding assays, Western immunoblotting, and reverse transcription-PCR analyses
      were used to investigate LHRH receptors in MRI-H255 and MRI-H187 transplantable
      human melanoma tumor lines. Antitumor effects of AN-207 and its components were
      evaluated in vivo in nude mice bearing xenografts of either melanoma tumor line.
      All 19 human melanoma specimens examined showed positive staining for LHRH
      receptors. The mRNA for LHRH receptors, receptor protein and binding sites for
      LHRH were detected in both transplantable melanoma tumor lines. AN-207
      significantly inhibited the growth of MRI-H255 and MRI-H187 xenografts in vivo,
      reducing tumor volume by 59.9% to 79.2% and tumor weight by 61.0% to 76.9% (all P
      < 0.05). The components of AN-207 (LH-RH analogue carrier and cytotoxic radical
      AN-201 as single drugs or as an unconjugated mixture) had no significant effects.
      Blockade of LHRH receptors by an excess of LHRH agonist Decapeptyl suppressed the
      effects of AN-207. LHRH receptors are expressed in a very high percentage of
      human malignant melanoma specimens and can be used for targeted chemotherapy with
      cytotoxic LHRH analogue AN-207.

PMID- 15994964
TI  - Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor
      growth by inhibiting angiogenesis in a vascular endothelial growth factor
      independent manner.
AB  - The interaction between the chemokine receptor CXCR4 and its specific ligand,
      stromal cell-derived factor-1 (SDF-1/CXCL12), mediates several cellular
      functions. In cancer, SDF-1-positive or CXCR4-positive cells of various lineages
      are detected within tumor tissues. Recent intensive research has indicated the
      possibility that blocking CXCR4 could reduce the metastatic potential of cancer
      cells. Here, we show that the inhibition of the SDF-1/CXCR4 axis decreases the
      growth of s.c. gastrointestinal tumors through the suppression of tumor
      neoangiogenesis. The neutralization of CXCR4 suppressed the growth in vivo of
      tumors derived from mouse Colon38 and PancO2 cells, whereas it did not affect the
      growth of Colon38 and PancO2 cells in vitro. This attenuation of tumor growth was
      found to be independent of the expression of CXCR4 by the cancer cells
      themselves, because CXCR4 knocked-down Colon38 cells grew similarly to control
      cells. Furthermore, CD31-positive tumor capillaries were reduced to 45% (P <
      0.001) and intratumor blood flows were decreased to 65% (P < 0.01) by blockade of
      CXCR4. The vascular endothelial growth factor (VEGF) concentration in the tumors
      was not affected by the neutralization of CXCR4. Taken together with the
      detection of CXCR4-positive endothelial cells in the tumor tissues, the findings
      suggest that the antiangiogenic effects of the blockade of CXCR4 are related to a
      reduction of the establishment of tumor endothelium independently of VEGF
      inhibition. Our data indicate that the SDF-1/CXCR4 pathway might be a general
      target for anticancer strategies and that blocking this system could be
      cooperatively effective in combination with other antiangiogenic therapies, such
      as blockade of VEGF.

PMID- 15994965
TI  - Noninvasive magnetic resonance thermography of recurrent rectal carcinoma in a
      1.5 Tesla hybrid system.
AB  - To implement noninvasive thermometry, we installed a hybrid system consisting of
      a radiofrequency multiantenna applicator (SIGMA-Eye) for deep hyperthermia (BSD
      2000/3D) integrated into the gantry of a 1.5 Tesla magnetic resonance (MR)
      tomograph Symphony. This system can record MR data during radiofrequency heating
      and is suitable for application and evaluation of methods for MR thermography. In
      15 patients with preirradiated pelvic rectal recurrences, we acquired phase data
      sets (25 slices) every 10 to 15 minutes over the treatment time (60-90 minutes)
      using gradient echo sequences (echo time = 20 ms), transformed the phase
      differences to MR temperatures, and fused the color-coded MR-temperature
      distributions with anatomic T1-weighted MR data sets. We could generate one
      complete series of MR data sets per patient with satisfactory quality for further
      analysis. In fat, muscle, water bolus, prostate, bladder, and tumor, we
      delineated regions of interest (ROI), used the fat ROI for drift correction by
      transforming these regions to a phase shift zero, and evaluated the MR
      temperature frequency distributions. Mean MR temperatures (T(MR)), maximum T(MR),
      full width half maximum (FWHM), and other descriptors of tumors and normal
      tissues were noninvasively derived and their dependencies outlined. In 8 of 15
      patients, direct temperature measurements in reference points were available. We
      correlated the tumor MR temperatures with direct measurements, clinical response,
      and tumor features (volume and location), and found reasonable trends and
      correlations. Therefore, the mean T(MR) of the tumor might be useful as a
      variable to evaluate the quality and effectivity of heat treatments, and
      consequently as optimization variable. Feasibility of noninvasive MR thermography
      for regional hyperthermia has been shown and should be further investigated.

PMID- 15994966
TI  - Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on
      RNA interference of vascular endothelial cell growth factor A.
AB  - Vascular endothelial cell growth factor A (VEGF-A) and hypoxia play important
      roles in tumor angiogenesis. VEGF-A gene expression is up-regulated in tumors
      under hypoxic conditions, yet it is unclear how such up-regulation will affect
      the efficacy of RNA interference strategies targeting VEGF-A. Four potential
      short interfering RNA (siRNA) sequences for the VEGF-A gene were cloned into
      expression plasmids and transfected into HT1080 human fibrosarcoma cells. Stable
      transfection of these plasmids decreased VEGF-A mRNA levels and protein secretion
      by up to 99%. Our analysis of >100 hypoxia-related genes using oligonucleotide
      microarrays of 38 human sarcoma samples and 14 normal tissues identified
      distinctly different patterns of expression between sarcomas and normal tissues
      as assessed by hierarchical clustering analysis. Numerous hypoxia-related genes
      were significantly up-regulated in sarcomas including hypoxia-inducible factor
      1alpha (HIF-1alpha). Exposure of wild-type HT1080 cells to 1% hypoxia resulted in
      HIF-1alpha up-regulation and a 74% increase in VEGF-A secretion as compared with
      secretion under normoxic conditions. Surprisingly, stable cell lines expressing
      VEGF-A siRNAs silenced VEGF-A expression equally well in hypoxia and normoxia.
      S.c. injection of cells with VEGF-A siRNAs into athymic nude mice led to slower
      growing tumors, decreased blood vessel density, and greater apoptosis when
      compared with controls. Immunofluorescence analysis of tumor sections revealed
      areas of HIF-1alpha nuclear expression, suggesting areas of hypoxia, in both
      control tumors and VEGF-suppressed tumors. We conclude that hypoxia plays an
      important role in human sarcomas but hypoxic up-regulation of VEGF-A expression
      does not attenuate the efficacy of VEGF-A RNA interference.

PMID- 15994967
TI  - Genome-wide screen identifies genes whose inactivation confer resistance to
      cisplatin in Saccharomyces cerevisiae.
AB  - To identify novel genes that mediate cellular resistance to cisplatin, we have
      screened the collection of Saccharomyces cerevisiae deletion strains. We have
      found reproducibly 22 genes/open reading frames (ORF), which when deleted, confer
      resistance to cisplatin at a concentration that is lethal to wild-type cells.
      Complementation of individual deletion strains with the corresponding wild-type
      gene abolished cisplatin resistance, confirming that specific gene deletions
      caused the resistance. Twenty of the genes/ORFs identified have not been
      previously linked to cisplatin resistance and belong to several distinct
      functional groups. Major functional groups encode proteins involved in nucleotide
      metabolism, mRNA catabolism, RNA-polymerase-II-dependent gene regulation and
      vacuolar transport systems. In addition, proteins that function in
      ubiquitination, sphingolipid biogenesis, cyclic AMP-dependent signaling, DNA
      repair, and genome stability are also associated with cisplatin resistance. More
      than half of the identified genes are known to have sequences or functional
      homology to mammalian counterparts. Some deletion strains are cross-resistant to
      selected cytotoxic agents whereas hypersensitive to others. The sensitivity of
      certain resistant strains to other cytotoxic agents suggests that our findings
      may point to particular drug combinations that can overcome resistance caused by
      inactivation of specific genes.

PMID- 15994968
TI  - Human anti-CD40 antagonist antibody triggers significant antitumor activity
      against human multiple myeloma.
AB  - Monoclonal antibodies (mAb) directed against lineage-specific B-cell antigens
      have provided clinical benefit for patients with hematologic malignancies, but to
      date no antibody-mediated immunotherapy is available for multiple myeloma. In the
      present study, we assessed the efficacy of a fully human anti-CD40 mAb CHIR-12.12
      against human multiple myeloma cells. CHIR-12.12, generated in XenoMouse mice,
      binds to CD138-expressing multiple myeloma lines and freshly purified CD138
      expressing cells from >80% multiple myeloma patients, as assessed by flow
      cytometry. Importantly, CHIR-12.12 abrogates CD40L-induced growth and survival of
      CD40-expressing patient multiple myeloma cells in the presence or absence of bone
      marrow stromal cells (BMSC), without altering constitutive multiple myeloma cell
      proliferation. Immunoblotting analysis specifically showed that PI3-K/AKT,
      nuclear factor-kappaB (NF-kappaB), and extracellular signal-regulated kinase
      activation induced by CD40L (5 mug/mL) was inhibited by CHIR-12.12 (5 mug/mL).
      Because CD40 activation induces multiple myeloma cell adhesion to both
      fibronectin and BMSCs, we next determined whether CHIR-12.12 inhibits this
      process. CHIR-12.12 decreased CD40L-induced multiple myeloma cell adhesion to
      fibronectin and BMSCs, whereas control human IgG1 did not. Adhesion of multiple
      myeloma cells to BMSCs induces interleukin-6 (IL-6) and vascular endothelial
      growth factor (VEGF) secretion, and treatment of multiple myeloma cells with
      CD40L further enhanced adhesion-induced cytokine secretion; conversely, CHIR
      12.12 blocks CD40L-enhanced IL-6 and VEGF secretion in cocultures of multiple
      myeloma cells with BMSCs. Finally, CHIR-12.12 triggered lysis of multiple myeloma
      cells via antibody-dependent cellular cytotoxicity (ADCC) but did not induce ADCC
      against CD40-negative multiple myeloma cells, confirming specificity against CD40
      expressing multiple myeloma cells. These results provide the preclinical
      rationale for clinical trials of CHIR-12.12 to improve patient outcome in
      multiple myeloma.

PMID- 15994970
TI  - Enhancement of 5-fluorouracil sensitivity by an rTS signaling mimic in H630 colon
      cancer cells.
AB  - The rTSbeta protein has been hypothesized to synthesize signaling molecules that
      can down-regulate thymidylate synthase. These molecules share biological and
      chemical properties with acyl-homoserine lactones (AHL), suggesting some AHLs
      might act as rTS signaling mimics and down-regulate thymidylate synthase. We have
      determined that the AHL, 3-oxododecanoyl homoserine lactone (3-oxo-C12-(L)-HSL)
      can down-regulate thymidylate synthase protein at 10 micromol/L and reduce H630
      (human colorectal cancer) growth by 50% at 23 micromol/L (IC50) in cell culture.
      At its IC50 concentration, 3-oxo-C12-(L)-HSL reduces the apparent IC50 of 5
      fluorouracil (5-FU) from 1 micromol/L to 80 nmol/L (12-fold) in a colony
      formation assay. 3-Oxo-C12-(L)-HSL enhances the activity of 5-fluorodeoxyuridine,
      tomudex, and taxol but not the activity of 5-fluorouridine, methotrexate or
      Adriamycin. The unexpected interaction with taxol probably results from effects
      of the AHL on tubulin expression. Differences in taxol sensitivity, tubulin, and
      cellular morphology between H630 and the thymidylate synthase and rTSbeta
      overproducing, 5-FU-resistant H630-1 cell line as determined by colony formation
      assays, Western analysis of one-dimensional and two-dimensional gels, and
      photomicroscopy confirm that cytoskeletal changes are induced by the AHL or by
      rTS signaling. Isozyme differences in thymidylate synthase and rTSbeta also exist
      in the two cell lines. Phosphorylation of rTSbeta amino acid S121 is shown to
      occur and is decreased at least 10-fold in the drug-resistant cells. The data
      presented provide support for further investigations of rTS signaling mimics as
      enhancers to thymidylate synthase-directed chemotherapy, evidence that the
      phosphorylation state of rTSbeta may be a marker for 5-FU resistance and a
      previously unrealized relationship between rTS signaling and the cytoskeleton.

PMID- 15994969
TI  - Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo
      imaging.
AB  - We have recently described the in vivo properties of an iodinated anti-p185HER2
      engineered antibody fragment [minibody (scFv-C(H)3)2; 80 kDa], made from the
      internalizing 10H8 monoclonal antibody. Although the 10H8 minibody showed
      excellent binding to the target in vitro, only modest tumor uptake [5.6 +/- 1.7%
      injected dose per gram (ID/g) of tissue] was achieved in nude mice bearing
      MCF7/HER2 breast cancer tumors. Here, in an attempt to improve targeting, the
      10H8 minibody was conjugated to 1,4,7,10-tetraazacyclododecane-N, N', N'', N'''
      tetraacetic acid (DOTA), radiometal labeled, and evaluated in vivo. The tumor
      uptake of 111In-DOTA 10H8 minibody was 5.7 +/- 0.1% ID/g, similar to the
      radioiodinated 10H8 minibody. However, in addition to the expected liver
      clearance, the kidneys had unexpectedly high activity (34.0 +/- 4.0% ID/g). A
      minibody derived from a second anti-p185(HER2) antibody (trastuzumab; hu4D5v8)
      was also made. Tumor uptakes, evaluated by quantitative microPET using 64Cu-DOTA
      hu4D5v8 minibody, were 4.2 +/- 0.5% ID/g. Furthermore, in non-tumor-bearing mice,
      111In-DOTA hu4D5v8 minibody exhibited similar elevated uptake in the kidneys
      (28.4 +/- 6.5% ID/g). Immunohistochemical staining of kidneys from non-tumor
      bearing mice showed strong specific staining of the proximal tubules, and Western
      blot analysis of kidney lysate confirmed the presence of cross-reactive antigen.
      To further improve tumor uptake and normal tissue distribution, a larger hu4D5v8
      fragment [(scFv-C(H)2-C(H)3)2; 105 kDa] was made, engineered to exhibit rapid
      clearance kinetics. This fragment, when evaluated by microPET, exhibited improved
      tumor targeting (12.2 +/- 2.4% ID/g) and reduced kidney uptake (13.1 +/- 1.5%
      ID/g). Thus, by manipulating the size and format of anti-p185(HER2) antibody
      fragments, the kidney activity was reduced and high or low expression of p185HER2
      in xenografts could be distinguished by microPET imaging.

PMID- 15994971
TI  - Increased expression of germinal center-associated nuclear protein RNA-primase is
      associated with lymphomagenesis.
AB  - Lymphomas arise containing abnormalities of various differentiation stage
      specific molecules. In the study reported here, we have shown abnormal up
      regulation of germinal center B cell-associated GANP in various human lymphomas
      including mantle cell, diffuse large B cell, and Hodgkin lymphoma, by
      immunohistochemical analysis. To study the role of GANP in lymphomagenesis, we
      generated mutant mice (ganp-Tg) that express the transgenic ganp gene under
      immunoglobulin enhancer and promoter control. Ganp-Tg mice showed a high
      incidence of lymphomagenesis (29.5%) after aging with a non-B/non-T cell surface
      phenotype having slight CD45R/B220 expression and Ig transcripts of rearranged VH
      DH-JH IgH loci. Lymphomas generated in ganp-Tg mice displayed similar pathologic
      characteristics to mouse reticulum cell neoplasm or Hodgkin lymphoma-like
      lesions. The VH sequences of individual mice showed that the tumors proliferated
      from a single clone or oligoclones, as is found in human diffuse large B-cell
      lymphomas and Hodgkin lymphoma. These results suggest that GANP overexpression is
      a causative factor in the generation of B lymphomas.

PMID- 15994972
TI  - Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic
      antigen on colorectal cancer cells through dendritic cell-specific intercellular
      adhesion molecule-3-grabbing nonintegrin.
AB  - Dendritic cells play a pivotal role in the induction of antitumor immune
      responses. Immature dendritic cells are located intratumorally within colorectal
      cancer and intimately interact with tumor cells, whereas mature dendritic cells
      are present peripheral to the tumor. The majority of colorectal cancers
      overexpress carcinoembryonic antigen (CEA), and malignant transformation changes
      the glycosylation of CEA on colon epithelial cells, resulting in higher levels of
      Lewis(x) and de novo expression of Lewis(y) on tumor-associated CEA. Dendritic
      cells express the C-type lectin dendritic cell-specific intercellular adhesion
      molecule-3-grabbing nonintegrin (DC-SIGN) that has high affinity for
      nonsialylated Lewis antigens, so we hypothesized that DC-SIGN is involved in
      recognition of colorectal cancer cells by dendritic cells. We show that immature
      dendritic cells within colorectal cancer express DC-SIGN and that immature
      dendritic cells but not mature dendritic cells interact with tumor cells. DC-SIGN
      mediates these interactions through binding of Lewis(x) and Lewis(y)
      carbohydrates on CEA of colorectal cancer cells. In contrast, DC-SIGN does not
      bind CEA expressed on normal colon epithelium that contains low levels of Lewis
      antigens. This indicates that dendritic cells may recognize colorectal cancer
      cells through binding of DC-SIGN to tumor-specific glycosylation on CEA. Similar
      to pathogens that target DC-SIGN to escape immunosurveillance, tumor cells may
      interact with DC-SIGN to suppress dendritic cell functions.

PMID- 15994973
TI  - Haplotype loss of HLA class I antigen as an escape mechanism from immune attack
      in lung cancer.
AB  - One of tumor escape mechanisms from the host's immunosurveillance system (i.e., a
      haplotype loss of HLA class I antigens) has been detected in various tumor cells.
      We hypothesize that the majority of tumor cells with normal HLA class I
      expression were attacked and eradicated by CTLs, and only a minority with an
      abnormal expression of HLA class I antigens could escape the host's
      immunosurveillance system. Using HLA class I-transfected tumor variants as
      stimulators in A904L lung cancer cell line, which has a haplotype loss of HLA
      class I antigens, both the transfected HLA-A26 and HLA-B39-restricted CTL lines
      were induced from autologous lymphocytes. However, only one HLA-B39-restricted
      CTL clone (CTL G3b) was established, and it was then used to identify the
      antigen. SGT1B [suppressor of G2 allele of SKP1 (SGT1), suppressor of kinetochore
      protein (SKP1)] was identified as the antigen recognized by CTL G3b. Further
      experiments using 13 subclones from a primary culture of A904L were found to
      confirm our above-mentioned hypothesis. Tumor cells with a normal HLA class I
      expression may thus be killed by CTL at an early stage of carcinogenesis, and
      only tumor cells with a haplotype loss of HLA class I antigens can escape an
      immune attack and develop into clinical cancer.

PMID- 15994974
TI  - A single vaccination with polyomavirus VP1/VP2Her2 virus-like particles prevents
      outgrowth of HER-2/neu-expressing tumors.
AB  - Murine polyomavirus (MPyV) VP1 virus-like particles (VLPs), containing a fusion
      protein between MPyV VP2 and the extracellular and transmembrane domain of HER
      2/neu (Her2), Her2(1-683)PyVLPs, were tested for their ability to vaccinate
      against Her2-expressing tumors in two different in vivo models. Protection was
      assessed both against a lethal challenge with a BALB/c mammary carcinoma
      transfected with human Her2 (D2F2/E2) and against the outgrowth of autochthonous
      mammary carcinomas in BALB-neuT mice, transgenic for the activated rat Her2
      oncogene. A single injection of Her2(1-683)PyVLPs before tumor inoculation
      induced a complete rejection of D2F2/E2 tumor cells in BALB/c mice. Similarly, a
      single injection of Her2(1-683)PyVLPs at 6 weeks of age protected BALB-neuT mice
      with atypical hyperplasia from a later outgrowth of mammary carcinomas, whereas
      all controls developed palpable tumors in all mammary glands. VLPs containing
      only VP1 and VP2 did not induce protection. The protection elicited by Her2(1
      683)PyVLPs vaccination was most likely due to a cellular immune response because
      a Her2-specific response was shown in an ELISPOT assay, whereas antibodies
      against Her2 were not detected in any of the two models. The results show the
      feasibility of using MPyV-VLPs carrying Her2 fusion proteins as safe and
      efficient vaccines against Her2-expressing tumors.

PMID- 15994975
TI  - Therapeutic vaccination against murine lymphoma by intratumoral injection of
      naive dendritic cells.
AB  - Dendritic cells are potent antigen-presenting cells that can induce both immune
      responses and tolerance depending on their state of activation. Immunologic
      tolerance to established tumors is a major impediment for the development of
      effective cancer immunotherapy. Dendritic cells may be deficient in number or in
      function at the tumor site. To address this problem, we evaluated the ability of
      immature naive dendritic cells to induce an antitumor immune response when
      injected directly into a murine B-cell lymphoma. Mice with advanced transplanted
      syngeneic tumor were given intratumoral injections of bone marrow-derived
      dendritic cells. Intratumoral dendritic cell injection alone had no antitumor
      effect. Systemic chemotherapy alone resulted in only transient tumor regression.
      However, the intratumoral injection of dendritic cells after chemotherapy led to
      complete, long-term tumor regression in the majority of treated mice. This
      dendritic cell-mediated antitumor effect was systemic, resulting in simultaneous
      elimination of the tumor at second uninjected sites. In addition, it resulted in
      long-term memory with resistance to tumor rechallenge. Both CD4+ and CD8+ T cells
      are necessary for the antitumor effect. Furthermore, tumors that occasionally
      recurred in mice with initial complete tumor regression could be retreated by the
      same combined chemoimmunotherapy approach. These results show that immunotherapy
      can succeed in the setting of advanced lymphoma if dendritic cells are restored
      and loaded with tumor antigens in situ at a single tumor site.

PMID- 15994976
TI  - p300 regulates androgen receptor-independent expression of prostate-specific
      antigen in prostate cancer cells treated chronically with interleukin-6.
AB  - Prostate cancer is the most frequent non-skin cancer in men. Although the
      mechanisms involved in the progression of prostate cancer are not entirely
      understood, androgen receptor has been shown to play an important role. Androgen
      receptor is expressed in both early and late-stage prostate cancer. Also,
      androgen-regulated pathways are thought to be active as evidenced by elevated
      levels of prostate-specific antigen (PSA). In addition, several androgen receptor
      coactivators and cytokines are involved in prostate cancer progression. In this
      regard, we have shown previously that the coactivator p300 plays a major role in
      the androgen-independent activation of PSA by interleukin 6 (IL-6), a cytokine
      involved in late-stage prostate cancer. In this study, we investigated the role
      of p300 and its homologue CREB-binding protein in prostate cancer cells treated
      chronically with IL-6. We found that p300 but not CREB-binding protein induced
      activation of PSA in these cells and that the histone acetyltransferase activity
      of p300 was critical. This effect was independent of the presence of androgens or
      antiandrogens. Moreover, we found markedly reduced levels of androgen receptor in
      these cells and p300 transfection did not affect those levels, suggesting that
      the p300 effect on PSA could be bypassing the androgen receptor. Transfection
      with exogenous androgen receptor showed minimal response of PSA to androgens but
      higher response to p300. We found similar effects of p300 on the androgen
      response element III, which mediates the androgen receptor-dependent activation
      of PSA. Finally, we showed that p300 alone regulates expression of the endogenous
      PSA gene in the IL-6-treated cells. These findings reveal a new insight in the
      progression of prostate cancer, suggesting that coactivators, such as p300, play
      more important roles in late-stage prostate cancer, and could regulate androgen
      dependent genes in the absence or with very low levels of androgen receptor.

PMID- 15994977
TI  - Androgen receptor cytosine, adenine, guanine repeats, and haplotypes in relation
      to ovarian cancer risk.
AB  - Biological and epidemiologic evidence suggest that androgen or its receptor may
      play a role in ovarian cancer pathogenesis. The most notable genetic factor
      influencing androgen receptor (AR) activity is the functional cytosine, adenine,
      guanine (CAG) repeat in which length is inversely proportional to its
      transactivational activity. Additional genetic variation due to single nucleotide
      polymorphisms in the AR gene may be captured through haplotypes. We genotyped the
      CAG microsatellite and six haplotype-tagging single nucleotide polymorphisms
      (rs962458, rs6152, rs1204038, rs2361634, rs1337080, rs1337082) of the androgen
      receptor gene in 987 ovarian cancer cases and 1,034 controls from a study
      conducted in New Hampshire and eastern Massachusetts between May 1992 and July
      2003. We estimated haplotype frequencies and calculated odds ratios with 95%
      confidence intervals to evaluate the association between the haplotypes and the
      AR CAG microsatellite with ovarian cancer risk. We observed that carriage of two
      alleles with > or = 22 CAG repeats was associated with an increased risk of
      ovarian cancer compared with carriage of two alleles with <22 CAG repeats
      (covariate-adjusted odds ratios, 1.31; 95% confidence intervals, 1.01-1.69). Five
      common haplotypes in the AR gene were identified, but no association between
      these and ovarian cancer risk was observed. Our results suggest that possession
      of two long AR alleles (> or = 22 CAG repeats) may be associated with increased
      risk of ovarian cancer compared with women with two short AR alleles (<22 CAG
      repeats).

PMID- 15994978
TI  - Tobacco smoke stimulates the transcription of amphiregulin in human oral
      epithelial cells: evidence of a cyclic AMP-responsive element binding protein
      dependent mechanism.
AB  - Activation of epidermal growth factor receptor (EGFR)-mediated signaling has been
      implicated in the pathogenesis of tobacco smoke-induced cancers. Recently,
      elevated levels of amphiregulin, a ligand of the EGFR, were found in the oral
      mucosa of smokers. The main objective of this study was to elucidate the
      mechanism by which tobacco smoke induces amphiregulin. Treatment of a
      nontumorigenic human oral epithelial cell line (MSK-Leuk1) with a saline extract
      of tobacco smoke stimulated amphiregulin (AR) transcription resulting in
      increased amounts of amphiregulin mRNA and protein. Tobacco smoke stimulated the
      cyclic AMP (cAMP)-->protein kinase A (PKA) pathway leading to increased cAMP
      responsive element binding protein-dependent activation of AR transcription.
      These inductive effects of tobacco smoke were dependent on the aryl hydrocarbon
      receptor (AhR). In fact, alpha-naphthoflavone, an AhR antagonist, blocked tobacco
      smoke-mediated induction of binding of cAMP-responsive element binding protein to
      the AR promoter and thereby suppressed the induction of amphiregulin. Notably,
      treatment of MSK-Leuk1 cells with tobacco smoke or exogenous amphiregulin
      stimulated DNA synthesis. An inhibitor of EGFR tyrosine kinase or a neutralizing
      antibody to amphiregulin abrogated the increase in DNA synthesis mediated by
      tobacco smoke. Taken together, these findings suggest that tobacco smoke
      stimulated a signaling pathway comprised of AhR-->cAMP-->PKA resulting in
      enhanced AR transcription and increased DNA synthesis. The ability of tobacco
      smoke to induce amphiregulin and thereby enhance DNA synthesis is likely to
      contribute to the procarcinogenic effects of tobacco smoke.

PMID- 15994979
TI  - The research component in orthodontic education: sniffing out rats (SnOR).

PMID- 15994980
TI  - Three-part bi-maxillary osteotomy: a case report involving resorbable plates.
AB  - This case report describes a patient who presented with a severe class 2 skeletal
      discrepancy together with a Class II malocclusion and a large anterior open bite.
      The malocclusion and skeletal discrepancy were managed with a combination of
      orthodontic and orthognathic treatment. The orthognathic surgery was undertaken
      following orthodontic decompensation using sectional mechanics to allow a
      segmental bimaxillary osteotomy and genioplasty to be performed. Although the
      discrepancy was severe using this combination of treatment, a successful outcome,
      both facially and occlusally, was achieved.

PMID- 15994981
TI  - Photographic 'Kesling set-up'.
AB  - The following report details a technique for producing a digital 'Kesling-type
      setup', which can give the patients an indication of how their dentition will
      look at the end of orthodontic treatment. High quality digital photographs of the
      patients' teeth are probably easier for the patients to relate to than a set of
      doctored plaster models.

PMID- 15994982
TI  - Non-surgical treatment of Class III malocclusion in adults: two case reports.
AB  - Class III malocclusions are usually growth-related discrepancies, which often
      become more severe until growth is complete. The surgery can be part of the
      treatment plan. The purpose of this report is to review the orthodontic treatment
      of two patients with a Class III malocclusion who were treated non-surgically.
      The basis for this treatment approach is presented and the final treatment result
      reviewed. Important factors to consider when establishing a Class III molar
      relationship are discussed.

PMID- 15994983
TI  - TN3-a bracket positioning instrument.

PMID- 15994984
TI  - Fluorides, orthodontics and demineralization: a systematic review.
AB  - OBJECTIVES: To evaluate the effectiveness of fluoride in preventing white spot
      lesion (WSL) demineralization during orthodontic treatment and compare all modes
      of fluoride delivery. DATA SOURCES: The search strategy for the review was
      carried out according to the standard Cochrane systematic review methodology. The
      following databases were searched for RCTs or CCTs: Cochrane Clinical Trials
      Register, Cochrane Oral Health Group Specialized Trials Register, MEDLINE and
      EMBASE. Inclusion and exclusion criteria were applied when considering studies to
      be included. Authors of trials were contacted for further data. DATA SELECTION:
      The primary outcome of the review was the presence or absence of WSL by patient
      at the end of treatment. Secondary outcomes included any quantitative assessment
      of enamel mineral loss or lesion depth. DATA EXTRACTION: Six reviewers
      independently, in duplicate, extracted data, including an assessment of the
      methodological quality of each trial. DATA SYNTHESIS: Fifteen trials provided
      data for this review, although none fulfilled all the methodological quality
      assessment criteria. One study found that a daily NaF mouthrinse reduced the
      severity of demineralization surrounding an orthodontic appliance (lesion depth
      difference -70.0 microm; 95% CI -118.2 to -21.8 microm). One study found that use
      of a glass ionomer cement (GIC) for bracket bonding reduced the prevalence of WSL
      (Peto OR 0.35; 95% CI 0.15-0.84) compared with a composite resin. None of the
      studies fulfilled all of the methodological quality assessment criteria.
      CONCLUSIONS: There is some evidence that the use of a daily NaF mouthrinse or a
      GIC for bonding brackets might reduce the occurrence and severity of WSL during
      orthodontic treatment. More high quality, clinical research is required into the
      different modes of delivering fluoride to the orthodontic patient.

PMID- 15994985
TI  - Orthodontic Clinical Trials III: reporting of ethical issues associated with
      clinical trials published in three orthodontic journals between 1989 and 1998.
AB  - AIMS: The aims of this study were to assess whether reports of orthodontic
      clinical trials complied with the requirements of the Declaration of Helsinki.
      DESIGN: A retrospective observational study. SETTING: The American Journal of
      Orthodontics and Dentofacial Orthopedics (AJODO), Journal of Orthodontics
      (formerly and up until 1999 known as the British Journal of Orthodontics, BJO)
      and European Journal of Orthodontics (EJO). DATA SOURCE: Clinical trials
      published between 1989 and 1998. METHODS: A hand search was performed to identify
      all clinical trials. Each trial report was assessed for inclusion of a statement
      that ethical approval and/or informed consent had been obtained. RESULTS: One
      hundred-and-fifty-five papers were identified, of which 85 (54.8%) were reports
      of randomized controlled trials (RCTs) and 70 (45.2%) of controlled clinical
      trials (CCTs). 16.1% (25/155), of the trial reports stated that ethical approval
      had been obtained and a quarter (39/155, 25.1%) indicated that informed consent
      had been obtained. CONCLUSIONS: Most orthodontic clinical trial reports failed to
      state whether ethical approval and/or informed consent had been obtained. The
      reporting of the ethical issues associated with orthodontic clinical trials could
      be improved further not only by the instructions to authors in orthodontic
      journals stating the need for studies to comply with the Declaration of Helsinki,
      but also by Journal editors refusing to publish trials that do not comply.

PMID- 15994990
TI  - Aesthetic orthodontic brackets.
AB  - Due to an increasing demand for superior aesthetics during fixed appliance
      treatment, the use of aesthetic brackets has grown in popularity over recent
      years. Although often requested by patients, aesthetic brackets are not without
      their disadvantages. This article presents the currently available plastic and
      ceramic brackets and discusses the potential problems associated with each.
      Recent advances, introduced by manufacturers in an attempt to overcome their
      clinical disadvantages, are described.

PMID- 15994986
TI  - British Orthodontic Society, Chapman Prize Winner 2003. A novel in vitro culture
      model to investigate the reaction of the dentine-pulp complex to orthodontic
      force.
AB  - OBJECTIVE: To develop a novel mandible slice organ culture model to investigate
      the effects of externally applied force on the dentine-pulp complex. DESIGN: In
      vitro organ culture. SETTING: School of Dentistry, Birmingham, UK. MATERIALS AND
      METHODS: Transverse 2 mm thick sections were cut from the mandibles of five 28
      day-old male Wistar rats. Serial sections were used for control and test pairs.
      Springs made from 0.016-inch and 0.019 x 0.025-inch stainless steel wires were
      used to apply a 50 g tensile or compressive force, respectively, to test
      specimens. Control and test specimens were cultured for 5 days in a humidified
      incubator with 5% CO(2) at 37 degrees C and processed for routine histological
      investigation. Nine more rats were used to provide control and compression test
      pairs where the pulps were extirpated after 3 days culture and total RNA isolated
      for gene expression analysis by reverse transcriptase polymerase chain reaction
      (RT-PCR). RESULTS: Histology showed the dental and supporting tissues maintained
      a healthy appearance in the control cultures after culture. Histomorphometric
      analysis revealed a 20-27% increase in pulp fibroblast density in test specimens
      compared with controls. Gene expression analyses revealed up-regulation in the
      test groups of PCNA, c-Myc, Collagen 1alpha, TGF-beta1 and alkaline phosphatase,
      whilst expression of osteocalcin was reduced. CONCLUSIONS: The results
      demonstrated that the present organ culture technique provides a valuable in
      vitro experimental model for studying the effects of externally applied forces.
      These forces stimulated a cellular response in the pulp chamber characterized by
      altered gene expression and proliferation of fibroblasts; the latter being
      unaffected by the nature of the force in terms of compression or tension.

PMID- 15994993
TI  - School failure: assessment, intervention, and prevention in primary pediatric
      care.

PMID- 15994994
TI  - Adenoviruses.

PMID- 15994995
TI  - Managing adolescent acne: a guide for pediatricians.

PMID- 15994996
TI  - Index of suspicion.

PMID- 15994997
TI  - Pulmonary arterial hypertension: diagnosis with fast perfusion MR imaging and
      high-spatial-resolution MR angiography--preliminary experience.
AB  - PURPOSE: To determine prospectively the accuracy of a magnetic resonance (MR)
      perfusion imaging and MR angiography protocol for differentiation of chronic
      thromboembolic pulmonary arterial hypertension (CTEPH) and primary pulmonary
      hypertension (PPH) by using parallel acquisition techniques. MATERIALS AND
      METHODS: The study was approved by the institution's internal review board, and
      all patients gave written consent prior to participation. A total of 29 patients
      (16 women; mean age, 54 years +/- 17 [+/- standard deviation]; 13 men; mean age,
      57 years +/- 15) with known pulmonary hypertension were examined with a 1.5-T MR
      imager. MR perfusion imaging (temporal resolution, 1.1 seconds per phase) and MR
      angiography (matrix, 512; voxel size, 1.0 x 0.7 x 1.6 mm) were performed with
      parallel acquisition techniques. Dynamic perfusion images and reformatted three
      dimensional MR angiograms were analyzed for occlusive and nonocclusive changes of
      the pulmonary arteries, including perfusion defects, caliber irregularities, and
      intravascular thrombi. MR perfusion imaging results were compared with those of
      radionuclide perfusion scintigraphy, and MR angiography results were compared
      with those of digital subtraction angiography (DSA) and/or contrast material
      enhanced multi-detector row computed tomography (CT). Sensitivity, specificity,
      and diagnostic accuracy of MR perfusion imaging and MR angiography were
      calculated. Receiver operator characteristic analyses were performed to compare
      the diagnostic value of MR angiography, MR perfusion imaging, and both modalities
      combined. For MR angiography and MR perfusion imaging, kappa values were used to
      assess interobserver agreement. RESULTS: A correct diagnosis was made in 26 (90%)
      of 29 patients by using this comprehensive MR imaging protocol. Results of MR
      perfusion imaging demonstrated 79% agreement (ie, identical diagnosis on a per
      patient basis) with those of perfusion scintigraphy, and results of MR
      angiography demonstrated 86% agreement with those of DSA and/or CT angiography.
      Interobserver agreement was good for both MR perfusion imaging and MR angiography
      (kappa = 0.63 and 0.70, respectively). CONCLUSION: The combination of fast MR
      perfusion imaging and high-spatial-resolution MR angiography with parallel
      acquisition techniques enables the differentiation of PPH from CTEPH with high
      accuracy.

PMID- 15994998
TI  - Chance-type flexion-distraction injuries in the thoracolumbar spine: MR imaging
      characteristics.
AB  - PURPOSE: To evaluate retrospectively the magnetic resonance (MR) imaging features
      of Chance-type flexion-distraction injuries. MATERIALS AND METHODS: The authors'
      institutional review board does not require its approval or patient informed
      consent for retrospective studies. Imaging data were reviewed retrospectively for
      24 patients (15 male, nine female; mean age, 28 years; range, 9-71 years) who had
      sustained radiographically typical Chance-type flexion-distraction injuries. The
      posterior vertebral body height remained unchanged or was increased in these
      patients. Two radiologists recorded a variety of bone and soft-tissue
      abnormalities seen with MR imaging. Based on consensus, the documented findings
      were sequentially analyzed to determine their frequencies. RESULTS: Combined bone
      and soft-tissue injuries occurred in 23 (96%) of 24 patients, were more common
      than soft-tissue damage alone (one [4%] of 24 patients), and occurred primarily
      at the thoracolumbar junction. Contiguous vertebral injury was seen in 20 (83%)
      of 24 patients, usually in the form of anterosuperior vertebral endplate edema,
      while noncontiguous injury occurred in eight (33%) of 24 patients. Extensive
      subcutaneous and paraspinal muscle edema was seen in all patients and extended
      over several segments. Posterior osteoligamentous complex disruption also
      occurred in all patients. Horizontally oriented fractures of the posterior neural
      arches produced an MR imaging pattern that the authors call the sandwich sign,
      which consists of linear hemorrhage framed by marrow edema. This sign was seen in
      12 (50%) of 24 patients. In seven (29%) of 24 patients, a fracture line extending
      from a damaged pedicle was seen to exit through the contralateral posterosuperior
      aspect of the vertebral body, with extension of the fracture fragments into the
      spinal canal. CONCLUSION: A spectrum of features is discernible with MR imaging
      in Chance-type injuries.

PMID- 15994999
TI  - Outcome of first-trimester pregnancies with slow embryonic heart rate at 6-7
      weeks gestation and normal heart rate by 8 weeks at US.
AB  - PURPOSE: To determine retrospectively the outcome of pregnancies in which the
      embryo has a slow heart rate at 6.0-7.0 weeks gestation and a normal heart rate
      at follow-up ultrasonography (US) by 8.0 weeks gestation. MATERIALS AND METHODS:
      Institutional review board approval was granted; informed consent was not
      required. The study was Health Insurance Portability and Accountability Act
      compliant. Singleton pregnancies with an embryonic heart rate measured on a 6.0
      7.0-week US scan were identified. The heart rate was classified as slow if it was
      fewer than 90 beats per minute prior to 6.3 weeks or fewer than 110 beats/min at
      6.3-7.0 weeks, normal if it was 100 or more beats/min at less than 6.3 weeks or
      120 or more beats/min at 6.3-7.0 weeks, or borderline if it was 90-99 beats/min
      prior to 6.3 weeks or 110-119 beats/min at 6.3-7.0 weeks. Pregnancies were
      excluded from the analysis if they were lost to follow-up before the end of first
      trimester. The Fisher exact test was used for all statistical comparisons.
      RESULTS: The rates of first-trimester demise were 60.6% for pregnancies with slow
      heart rates at 6.0-7.0 weeks (188 of 310), 17.4% for those with borderline heart
      rates (103 of 593), and 9.1% for those with normal heart rates (186 of 2034).
      There were 59 pregnancies with a slow heart rate at 6.0-7.0 weeks and a normal
      heart rate at follow-up US by 8.0 weeks; 15 (25.4%) resulted in first-trimester
      demise. This rate of demise was significantly higher than that of 7.2% (28 of
      390) in pregnancies with a normal heart rate at 6.0-7.0 weeks and a normal heart
      rate by 8.0 weeks (P <.001, Fisher exact test). Pregnancies with a borderline
      heart rate early in pregnancy followed by a normal heart rate had a demise rate
      of 7.6% (nine of 118), which is similar to those with normal heart rates early in
      pregnancy followed by normal heart rates at follow-up (P = .84). CONCLUSION: When
      a slow embryonic heart rate is detected at 6.0-7.0 weeks, the likelihood of
      subsequent first-trimester demise remains elevated (approximately 25%) even if
      the heart rate is normal at follow-up. In such pregnancies, at least one follow
      up scan in late first trimester is warranted.

PMID- 15995000
TI  - Artificially induced pneumothorax for percutaneous transthoracic radiofrequency
      ablation of tumors in the hepatic dome: initial experience.
AB  - After institutional review board approval, informed consent was obtained from six
      patients (four men and two women, aged 47-74 years) with a total of six tumors of
      the liver dome. These patients were treated by means of radiofrequency (RF)
      ablation with computed tomographic (CT) guidance and a transthoracic approach.
      With use of general anesthesia, a right pneumothorax was induced by means of
      manual injection of air until the route allowing access to the tumor was cleared
      of all lung parenchyma. Then RF ablation was performed with transthoracic
      extrapulmonary transdiaphragmatic access. After retrieval of the RF electrode,
      the pneumothorax was fully aspirated. All procedures were successfully performed
      without complications. Artificially induced pneumothorax appears useful and safe
      for CT-guided RF ablation of liver dome tumors, although this experience was
      minimal, with only six patients treated.

PMID- 15995002
TI  - Identification of a gene in the process of being lost from the genus Agrostis.
AB  - Lineage-specific gene loss is considered one of the processes contributing to
      speciation and genome diversity. Such gene loss has been inferred from
      interspecies comparisons of orthologous DNA segments. Examples of intraspecific
      gene loss are rare. Here we report identification of a gene, designated Crs-1
      (creeping specific-1), that appears to be in the process of being lost from
      heterozygous populations of the species creeping bentgrass (Agrostis
      stolonifera). The Crs-1 gene encodes a protein with an N-terminal dirigent
      protein domain and a C-terminal lectin domain and is similar to the maize (Zea
      mays) beta-glucosidase aggregating factor. Most individual creeping bentgrass
      plants examined are lacking Crs-1. Some individuals are hemizygous for the Crs-1
      locus, indicating major haplotype noncolinearity at that locus. Crs-1 was not
      detected in several other Agrostis species, indicating it is being lost from the
      genus. The Crs-1 locus in creeping bentgrass provides a rare example of the
      evolutionary process of gene loss occurring within a plant species.

PMID- 15995003
TI  - Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates
      the outcome of nonrotavirus diarrhea in children from Bangladesh.
AB  - BACKGROUND: Previous studies have shown that selected strains of lactobacilli
      that are administered orally result in a modest reduction of diarrhea duration.
      However, duration alone is not considered optimal for therapeutic evaluation of
      any agent in diarrhea. OBJECTIVE: To examine the effect of a new probiotic,
      Lactobacillus paracasei strain ST11 (ST11), in acute childhood diarrhea by using
      evaluation criteria recommended by the World Health Organization. METHODS: In a
      randomized, double-blind, placebo-controlled clinical trial, 230 male infants and
      young children, 4 to 24 months of age, presenting with diarrhea of <2 days'
      duration were admitted to the metabolic research ward of the International Centre
      for Diarrheal Disease Research, Bangladesh, and fed 10(10) colony-forming units
      of lyophilized ST11 or placebo daily for 5 days. Stool output and frequency, oral
      rehydration solution intake, and excretion of rotavirus were monitored daily.
      RESULTS: No effect of ST11 treatment on severe rotavirus diarrhea was observed.
      However, the probiotic treatment did significantly reduce cumulative stool output
      (225 +/- 218 vs 381 +/- 240 mL/kg), stool frequency (27.9 +/- 17 vs 42.5 +/- 26),
      and oral rehydration solution intake (180 +/- 207 vs 331 +/- 236 mL/kg) in
      children with less-severe nonrotavirus diarrhea compared with those receiving
      placebo treatment. A significantly higher proportion of nonrotavirus children
      receiving ST11 had their diarrhea resolve within 6 days of therapy (ST11 versus
      placebo: 76% vs 49%). CONCLUSIONS: ST11 has a clinically significant benefit in
      the management of children with nonrotavirus-induced diarrhea, but it is
      ineffective in those with rotavirus diarrhea.

PMID- 15995001
TI  - HEAT SHOCK PROTEIN 90C is a bona fide Hsp90 that interacts with plastidic HSP70B
      in Chlamydomonas reinhardtii.
AB  - We report on the molecular and biochemical characterization of HEAT SHOCK PROTEIN
      90C (HSP90C), one of the three Hsp90 chaperones encoded by the Chlamydomonas
      reinhardtii genome. Fractionation experiments indicate that HSP90C is a plastidic
      protein. In the chloroplast, HSP90C was localized to the soluble stroma fraction,
      but also to thylakoids and low-density membranes containing inner envelopes.
      HSP90C is expressed under basal conditions and is strongly induced by heat shock
      and moderately by light. In soluble cell extracts, HSP90C was mainly found to
      organize into dimers, but also into complexes of high molecular mass. Also,
      heterologously expressed HSP90C was mainly found in dimers, but tetramers and
      fewer monomers were detected, as well. HSP90C exhibits a weak ATPase activity
      with a Km for ATP of approximately 48 microM and a kcat of approximately 0.71
      min(-1). This activity was inhibited by the Hsp90-specific inhibitor radicicol.
      In coimmunoprecipitation experiments, we found that HSP90C interacts with several
      proteins, among them plastidic HSP70B. The cellular concentration of HSP70B was
      found to be 2.9 times higher than that of HSP90C, giving a 4.8:1 stoichiometry of
      HSP70B monomers to HSP90C dimers. The strong inducibility of HSP90C by heat shock
      implies a role of the chaperone in stress management. Furthermore, its
      interaction with HSP70B suggests that, similar to their relatives in cytosol and
      the endoplasmic reticulum, both chaperones might constitute the core of a
      multichaperone complex involved in the maturation of specific client proteins,
      e.g. components of signal transduction pathways.

PMID- 15995004
TI  - Distinctive distribution of pathogens associated with peritonitis in neonates
      with focal intestinal perforation compared with necrotizing enterocolitis.
AB  - OBJECTIVE: Candida and coagulase-negative staphylococci are emerging pathogens
      associated with focal intestinal perforation (FIP) and necrotizing enterocolitis
      (NEC) in neonates. The objective of this study was to determine whether there are
      significant differences in the predominant pathogens in culture-positive cases of
      peritonitis associated with FIP compared with NEC in neonates. METHODS: A
      retrospective cross-sectional study was conducted of neonates with peritoneal
      culture-positive peritonitis associated with FIP or NEC over a 12-year study
      period (1989-2000). Cases with peritonitis were identified from a microbiology
      database. NEC was defined by radiologic evidence of pneumatosis intestinalis or
      portal venous gas or by pathology reports or surgical operative notes describing
      large areas of transmural bowel necrosis. FIP was defined as a <1-cm intestinal
      perforation surrounded by otherwise normal tissue in the absence of NEC. RESULTS:
      Thirty-six cases of FIP were compared with 80 cases of NEC. Birth weight and
      gestational age were significantly lower in infants with FIP compared with NEC.
      Age at intestinal perforation and case fatality rates were similar between FIP
      and NEC. There were striking differences in the distribution of predominant
      pathogens associated with peritonitis in NEC and FIP cases. Enterobacteriaceae
      were present in 60 (75%) of 80 NEC cases compared with 9 (25%) of 36 FIP cases.
      In contrast, Candida species were found in 16 (44%) of 36 FIP cases compared with
      12 (15%) of 80 NEC cases, and coagulase-negative staphylococci were present in 18
      (50%) of 36 FIP cases versus 11 (14%) of 80 NEC cases. There were no significant
      differences between FIP and NEC cases for the presence of Enterococcus species
      (28% vs 23%) or anaerobes (3% vs 6%). Stratified analysis for birth weight <1200
      g found similar significant differences in the predominant pathogens for FIP (n =
      29) and NEC (n = 38). Results from peritoneal fluid cultures resulted in changes
      in antimicrobial therapy in 46 (40%) of 116 cases. CONCLUSIONS: Candida species
      and coagulase-negative staphylococci were the predominant pathogens in FIP
      peritonitis in contrast to Enterobacteriaceae in NEC peritonitis. A peritoneal
      fluid culture should be obtained in all neonates with intestinal perforation,
      regardless of cause, because it may help to direct the choice of the most
      effective antimicrobial.

PMID- 15995005
TI  - A vancomycin-heparin lock solution for prevention of nosocomial bloodstream
      infection in critically ill neonates with peripherally inserted central venous
      catheters: a prospective, randomized trial.
AB  - OBJECTIVE: Critically ill neonates are at high risk for vascular catheter-related
      bloodstream infection (CRBSI), most often caused by coagulase-negative
      staphylococci. Most CRBSIs with long-term devices derive from intraluminal
      contaminants. The objective of this study was to ascertain the safety and the
      efficacy of a vancomycin-heparin lock solution for prevention of CRBSI. METHODS:
      A prospective, randomized double-blind trial was conducted during 2000-2001 at a
      community hospital level III NICU. Very low birth weight and other critically ill
      neonates with a newly placed peripherally inserted central venous catheter were
      randomized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes
      with heparinized normal saline (n = 43) or heparinized saline that contained
      vancomycin 25 microg/mL (n = 42). The origin of each nosocomial bloodstream
      infection (BSI) was studied by culturing skin, catheter hubs, and implanted
      catheter segments and blood cultures, demonstrating concordance by restriction
      fragment DNA subtyping. Surveillance axillary and rectal cultures were performed
      to detect colonization by vancomycin-resistant organisms. The main outcome
      measures were (1) CRBSIs and (2) colonization or infection by vancomycin
      resistant Gram-positive bacteria. RESULTS: Two (5%) of 42 infants in the
      vancomycin-lock group developed a CRBSI as compared with 13 (30%) of 43 in the
      control group (2.3 vs 17.8 per 1000 catheter days; relative risk: 0.13; 95%
      confidence interval: 0.01-0.57). No vancomycin-resistant enterococci or
      staphylococci were recovered from any cultures. Vancomycin could not be detected
      in the blood of infants who did not receive systemic vancomycin therapy. Twenty
      six neonates (8 vancomycin-lock group, 18 control group) had at the end of a
      catheter-lock period asymptomatic hypoglycemia that resolved promptly when
      glucose-containing intravenous fluids were restarted. CONCLUSIONS: Prophylactic
      use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI
      in high-risk neonates with long-term central catheters and did not promote
      vancomycin resistance but was associated with asymptomatic hypoglycemia. The use
      of an anti-infective lock solution for prevention of CRBSI with long-term
      intravascular devices has achieved proof of principle and warrants selective
      application in clinical practice.

PMID- 15995006
TI  - Acute tellurium toxicity from ingestion of metal-oxidizing solutions.
AB  - Tellurium is an element used in the vulcanization of rubber and in metal
      oxidizing solutions to blacken or tarnish metals. Descriptions of human toxicity
      from tellurium ingestion are rare. We report the clinical course of 2 children
      who ingested metal-oxidizing solutions containing substantial concentrations of
      tellurium. Clinical features included vomiting, black discoloration of the oral
      mucosa, and a garlic odor to the breath. One patient developed corrosive injury
      to the esophagus secondary to the high concentration of hydrochloric acid in the
      solution. Both patients recovered without serious sequelae, which is typical of
      tellurium toxicity. An awareness of situations in which children may be exposed
      to tellurium and its clinical presentation may assist clinicians in the diagnosis
      of this rare poisoning.

PMID- 15995007
TI  - Prevention and control of meningococcal disease: recommendations for use of
      meningococcal vaccines in pediatric patients.
AB  - Two peaks in the incidence of invasive meningococcal disease (IMD) occur in
      pediatric patients: infants younger than 1 year and adolescents 15 to 18 years of
      age. Although the incidence of IMD is highest in infants, the case-fatality rate
      is highest in adolescents (approximately 20%). Epidemiologic studies also have
      demonstrated increased risk of IMD among college freshman living in dormitories
      compared with other college students and similarly aged persons in the general
      population. At least 75% of cases of IMD in 11- to 18-year-olds are caused by
      serogroups A, C, Y, and W-135; thus, IMD potentially is preventable by
      immunization with quadrivalent meningococcal vaccines. Meningococcal A, C, Y, W
      135 conjugate vaccine (MCV4) was licensed in 2005 for use in people 11 to 55
      years of age. On the basis of data indicating increased risk of meningococcal
      disease and fatality among certain adolescents and college students, the American
      Academy of Pediatrics recommends administration of MCV4 to young adolescents (at
      the 11- to 12-year visit), students entering high school or 15-year-olds, and
      college freshmen who will be living in dormitories. For pediatric patients 11
      years and older who are at increased risk of meningococcal disease, MCV4 also is
      recommended. The purposes of this statement are to provide the rationale for
      routine use of MCV4 in adolescents and to update recommendations for use of the
      meningococcal polysaccharide vaccine in pediatric patients.

PMID- 15995008
TI  - The cost of containing one case of measles: the economic impact on the public
      health infrastructure--Iowa, 2004.
AB  - BACKGROUND: In February 2004, students from a college in Iowa, with a high
      proportion of nonmedical exemptions to vaccination, traveled to India; one fourth
      of the students contracted measles while there. One exposed, susceptible student
      returned home during his infectious period, necessitating 2 months of containment
      efforts in Iowa. OBJECTIVE: The objective of this study was to measure the direct
      costs of measles containment from a public health system perspective. METHODS: We
      evaluated activities performed, personnel time/materials allocated, and direct
      costs incurred in 2004 US dollars by the Iowa public health infrastructure. The
      study period was defined as March 5, 2004 (when the Iowa Department of Public
      Health was first contacted about the case), through May 12, 2004 (when a final
      meeting was held on the containment effort). RESULTS: A total of 2525 hours of
      personnel time were expended to review flight manifests, contact exposed
      passengers, set up vaccination clinics, trace >1000 potentially exposed contacts,
      and institute and enforce quarantine orders for vaccination refusers. Two
      thousand twenty-five phone calls were received from the public, and 2243 miles
      were driven by staff. The temporal distribution of personnel time was
      characterized by marked peaks at the report of potential secondary cases. The
      total estimated cost was 142452 dollars. CONCLUSIONS: The direct cost to the
      public health infrastructure of containing 1 case of measles was far greater than
      the estimated cost of uncomplicated individual illness (less than 100 dollars).
      Economic analyses of vaccine-preventable diseases may need to go beyond the costs
      of individual illness to account for the costs of protecting society.

PMID- 15995009
TI  - Improvement in bone mineral density and body composition in survivors of
      childhood acute lymphoblastic leukemia: a 1-year prospective study.
AB  - OBJECTIVES: Abnormalities in bone mineral density (BMD), body composition, and
      bone metabolism have been reported in children who were treated for acute
      lymphoblastic leukemia (ALL) during and after completion of therapy. However,
      these studies are cross-sectional, and no longitudinal data are available in a
      large group of patients after completion of therapy. In the present study, 1-year
      longitudinal changes in BMD, body composition, and bone metabolism were evaluated
      in children with ALL during the first 3 years after completion of therapy without
      cranial irradiation. METHODS: BMD of total body (TB; g/cm(2)), areal and apparent
      volumetric lumbar spine (L2-L4), lean body mass, and percentage of body fat were
      measured by dual-energy x-ray absorptiometry in 37 children (median age: 7.9
      years; range: 4.7-20.6 years) who were treated for ALL at a median age of 3.3
      years (range: 1.1-16.6 years), after a median time of 2.2 years after the
      completion of treatment, and after a 1-year follow-up period. Two control
      subjects (n = 74) who were matched for gender, age, and pubertal stage were also
      longitudinally investigated for body composition for 1 year. Usual serum
      biochemical markers of calcium metabolism and bone turnover were measured in
      patients during the study period. RESULTS: A slight decrease in TB BMD was found
      after a median time of 2.2 years after the completion of therapy for ALL in
      childhood. Patients showed a significantly lower median TB BMD when evaluated
      <1.5 years as compared with those at >or=1.5 years since completion of therapy.
      At the time of first evaluation, the percentage of body fat mass was
      significantly higher and patients were physically less active than their matched
      control subjects. Although, as expected, during the 1 year of follow-up both
      groups showed an annual increment in their BMD measurements, a significantly
      higher increase in TB BMD was observed in patients in comparison with control
      subjects. During this same period, the increase in the percentage of body fat
      mass was slightly lower in ALL patients as compared with control subjects. At the
      end of the follow-up year, BMD, body-composition parameters, and physical
      activity of ALL patients were similar to those observed in matched control
      subjects. Serum biochemical markers of bone turnover were normal at both
      evaluations. CONCLUSIONS: A significant increase in TB BMD and a tendency to a
      lesser increase in percentage of body fat mass were observed during the study
      period in ALL patients as compared with chronological age-, gender-, and pubertal
      stage-matched control subjects. These findings suggest a positive effect of long
      term completion therapy and increase in physical activity on BMD, body
      composition, and bone metabolism in patients who have been treated for ALL.

PMID- 15995010
TI  - Heat stress from enclosed vehicles: moderate ambient temperatures cause
      significant temperature rise in enclosed vehicles.
AB  - OBJECTIVE: Each year, children die from heat stroke after being left unattended
      in motor vehicles. In 2003, the total was 42, up from a national average of 29
      for the past 5 years. Previous studies found that on days when ambient
      temperatures exceeded 86 degrees F, the internal temperatures of the vehicle
      quickly reached 134 to 154 degrees F. We were interested to know whether
      similarly high temperatures occurred on clear sunny days with more moderate
      temperatures. The objective of this study was to evaluate the degree of
      temperature rise and rate of rise in similar and lower ambient temperatures. In
      addition, we evaluated the effect of having windows "cracked" open. METHODS: In
      this observational study, temperature rise was measured continuously over a 60
      minute period in a dark sedan on 16 different clear sunny days with ambient
      temperatures ranging from 72 to 96 degrees F. On 2 of these days, additional
      measurements were made with the windows opened 1.5 inches. Analysis of variance
      was used to compare how quickly the internal vehicle temperature rose and to
      compare temperature rise when windows were cracked open 1.5 inches. RESULTS:
      Regardless of the outside ambient temperature, the rate of temperature rise
      inside the vehicle was not significantly different. The average mean increase was
      3.2 degrees F per 5-minute interval, with 80% of the temperature rise occurring
      during the first 30 minutes. The final temperature of the vehicle depended on the
      starting ambient temperature, but even at the coolest ambient temperature,
      internal temperatures reached 117 degrees F. On average, there was an
      approximately 40 degrees F increase in internal temperature for ambient
      temperatures spanning 72 to 96 degrees F. Cracking windows open did not decrease
      the rate of temperature rise in the vehicle (closed: 3.4 degrees F per 5 minutes;
      opened: 3.1 degrees F per 5 minutes or the final maximum internal temperature.
      CONCLUSIONS: Even at relatively cool ambient temperatures, the temperature rise
      in vehicles is significant on clear, sunny days and puts infants at risk for
      hyperthermia. Vehicles heat up rapidly, with the majority of the temperature rise
      occurring within the first 15 to 30 minutes. Leaving the windows opened slightly
      does not significantly slow the heating process or decrease the maximum
      temperature attained. Increased public awareness and parental education of heat
      rise in motor vehicles may reduce the incidence of hyperthermia death and improve
      child passenger safety.

PMID- 15995011
TI  - Water-pipe (narghile) smoking: an emerging health risk behavior.
AB  - Narghile, or water-pipe smoking (WPS), has been practiced extensively for
      approximately 400 years. It is common in the Arabian Peninsula, Turkey, India,
      Pakistan, and other countries. In recent years, there has been a revival of WPS,
      notably among youth. Most US health professionals are unfamiliar with the
      practice and health consequences of WPS. Therefore, this trend presents a new
      challenge for adolescent health care providers. The composition of the tobacco
      used in WPS is variable and not well standardized. Studies that have examined
      narghile smokers and the aerosol of narghile smoke have reported high
      concentrations of carbon monoxide, nicotine, "tar," and heavy metals. These
      concentrations were as high or higher than those among cigarette smokers. The few
      scientific data regarding the adverse health consequences of WPS point to dangers
      that are similar to those associated with cigarette smoking: malignancy, impaired
      pulmonary function, low birth weight, and others. Additional dangers not
      encountered with cigarette smoking are infectious diseases resulting from pipe
      sharing and the frequent addition of alcohol or psychoactive drugs to the
      tobacco. Public health strategies for controlling the emerging epidemic of WPS
      include carrying out epidemiologic and toxicologic research; implementation of
      laws to limit acquisition and use; and health education, targeting adolescents in
      particular.

PMID- 15995012
TI  - US Department of Education data on "autism" are not reliable for tracking autism
      prevalence.
AB  - Many autism advocacy groups use the data collected by the US Department of
      Education (USDE) to show a rapidly increasing prevalence of autism. Closer
      examination of these data to follow each birth-year cohort reveals anomalies
      within the USDE data on autism. The USDE data show not only a rise in overall
      autism prevalence with time but also a significant and nearly linear rise in
      autism prevalence within a birth-year cohort as it ages, with significant numbers
      of new cases as late as 17 years of age. In addition, an unexpected reduction in
      the rise of autism prevalence occurs in most cohorts at 12 years of age, the age
      when most children would be entering middle school. These anomalies point to
      internal problems in the USDE data that make them unsuitable for tracking autism
      prevalence.

PMID- 15995013
TI  - Screening and interventions for childhood overweight: a summary of evidence for
      the US Preventive Services Task Force.
AB  - BACKGROUND: Childhood and adolescent overweight and obesity are related to health
      risks, medical conditions, and increased risk of adult obesity, with its
      attendant effects on morbidity and mortality rates. The prevalence of childhood
      overweight and obesity has more than doubled in the past 25 years. Purpose. This
      evidence synthesis examines the evidence for the benefits and harms of screening
      and early treatment of overweight among children and adolescents in clinical
      settings. METHODS: We developed an analytic framework and 7 key questions
      representing the logical evidence connecting screening and weight control
      interventions with changes in overweight and behavioral, physiologic, and health
      outcomes in childhood or adulthood. We searched the Cochrane Library from 1996 to
      April 2004. We searched Medline, PsycINFO, DARE, and CINAHL from 1966 to April
      2004. One reviewer abstracted relevant information from each included article
      into standardized evidence tables, and a second reviewer checked key elements.
      Two reviewers quality-graded each article with US Preventive Services Task Force
      criteria. RESULTS: Although BMI is a measure of relative weight rather than
      adiposity, it is recommended widely for use among children and adolescents to
      determine overweight and is the currently preferred measure. The risk of adult
      overweight from childhood overweight provides the best available evidence to
      judge the clinical validity of BMI as an overweight criterion for children and
      adolescents. BMI measures in childhood track to adulthood moderately or very
      well, with stronger tracking seen for children with >or=1 obese parent and
      children who are more overweight or older. The probability of adult obesity (BMI
      of >30 kg/m(2)) is >or=50% among children >13 years of age whose BMI percentiles
      meet or exceed the 95th percentile for age and gender. BMI-based overweight
      categorization for individuals, particularly for racial/ethnic minorities with
      differences in body composition, may have limited validity because BMI measures
      cannot differentiate between increased weight for height attributable to
      relatively greater fat-free mass (muscle, bone, and fluids) and that attributable
      to greater fat. No trials of screening programs to identify and to treat
      childhood overweight have been reported. Limited research is available on
      effective, generalizable interventions for overweight children and adolescents
      that can be conducted in primary care settings or through primary care referrals.
      CONCLUSIONS: BMI measurements of overweight among older adolescents identify
      those at increased risk of developing adult obesity. Interventions to treat
      overweight adolescents in clinical settings have not been shown to have
      clinically significant benefits, and they are not widely available. Screening to
      categorize overweight among children under age 12 or 13 who are not clearly
      overweight may not provide reliable risk categorization for adult obesity.
      Screening in this age group is compromised by the fact that there is little
      generalizable evidence for primary care interventions. Because existing trials
      report modest short- to medium-term improvements (approximately 10-20% decrease
      in percentage of overweight or a few units of change in BMI), however, overweight
      improvements among children and adolescents seem possible.

PMID- 15995014
TI  - Risk factors associated with sudden unexplained infant death: a prospective study
      of infant care practices in Kentucky.
AB  - OBJECTIVE: To ascertain the prevalence of infant care practices in a metropolitan
      community in the United States with attention to feeding routines and modifiable
      risk factors associated with sudden unexplained infant death (specifically, prone
      sleeping position, bed sharing, and maternal smoking). METHODS: We conducted an
      initial face-to-face meeting followed by a telephone survey of 189 women who gave
      birth at a level I hospital in Kentucky between October 14 and November 10, 2002,
      and whose infants were placed in the well-infant nursery. The survey, composed of
      questions pertaining to infant care practices, was addressed to the women at 1
      and 6 months postpartum. RESULTS: A total of 185 (93.9%) women participated in
      the survey at 1 month, and 147 (75.1%) mothers contributed at 6 months. The
      racial/ethnic composition of the study was 56.1% white, 30.2% black, and 16.4%
      biracial, Asian, or Hispanic. More than half of the infants (50.8%) shared the
      same bed with their mother at 1 month, which dramatically decreased to 17.7% at 6
      months. Bed sharing was significantly more common among black families compared
      with white families at both 1 month (adjusted odds ratio [OR]: 5.94; 95%
      confidence interval [CI]: 2.71-13.02) and 6 months (adjusted OR: 5.43; 95% CI:
      2.05-14.35). Compared with other races, white parents were more likely to place
      their infants on their back before sleep at both 1 and 6 months. Black parents
      were significantly less likely to place their infants on their back at 6 months
      compared with white parents (adjusted OR: 0.14; 95% CI: 0.06-0.33). One infant
      succumbed to sudden infant death syndrome at 3 months of age, and another infant
      died suddenly and unexpectedly at 9 months of age. Both were bed sharing
      specifically with 1 adult in the former and with 2 children in the latter.
      CONCLUSIONS: Bed sharing and prone placement were more common among black
      infants. Breastfeeding was infrequent in all races. This prospective study
      additionally offers a unique perspective into the risk factors associated with
      sudden infant death syndrome and sudden unexplained infant death associated with
      bed sharing by examining the survey responses of 2 mothers before the death of
      their infants combined with a complete postmortem examination, scene analysis,
      and historical investigation.

PMID- 15995015
TI  - Factitious hyperinsulinism leading to pancreatectomy: severe forms of Munchausen
      syndrome by proxy.
AB  - Clinical history and inappropriate insulin secretion during hypoglycemic episodes
      permit the diagnosis of hyperinsulinism. We report 2 cases of factitious
      hyperinsulinism leading to partial pancreatectomy. Case 1 was an 8-year-old girl
      who presented with severe hypoglycemia and elevated insulin and C-peptide levels.
      Catheterization of pancreatic veins was performed to localize the excess insulin
      secretion. Insulinoma was suspected, and partial pancreatectomy was performed.
      Ten days after surgery, severe hypoglycemia recurred with severely elevated
      plasma insulin levels (x100) but very low C-peptide plasma levels, suggesting
      factitious hyperinsulinemia. Hypoglycemic episodes before surgery were provoked
      by oral sulfonamides; postoperative episodes were caused by parenteral insulin.
      Falsified prescriptions for sulfonamides and insulin by the mother, a nurse, were
      found. Case 2 was a 6-month-old girl who presented with seizures and hypoglycemia
      but had a symptom-free interval of many months afterward. At 2 years of age,
      repeated hypoglycemic seizures and elevated insulin plasma levels suggested
      congenital hyperinsulinism. C-peptide plasma level, measured once, was normal,
      but blood sampling was performed 15 minutes after a hypoglycemic episode. Partial
      pancreatectomy was performed. Two weeks after surgery, hypoglycemic seizures
      recurred, and the patient was admitted for pancreatic vein catheterization. This
      investigation was performed during hypoglycemia and revealed high insulin levels
      and undetectable C-peptide levels, suggesting factitious hypoglycemia. Insulin/C
      peptide ratio analysis is crucial to assess factitious hypoglycemia, although
      sulfonamide-induced hypoglycemia is not thereby detected. One percent (2 of 250)
      of all cases of hyperinsulinemic hypoglycemia in our unit have been identified as
      Munchausen syndrome by proxy. Atypical disease history should raise the question
      of factitious hypoglycemia.

PMID- 15995016
TI  - Bullous "cellulitis" with eosinophilia: case report and review of Wells' syndrome
      in childhood.
AB  - A 1-year-old girl presented with acute onset of edematous erythematous plaques
      associated with bullae on her extremities and accompanied by peripheral
      eosinophilia. She was afebrile, and the skin lesions were pruritic but not
      tender. The patient was treated with intravenously administered antibiotics for
      presumed cellulitis, without improvement. However, the lesions responded rapidly
      to systemic steroid therapy. On the basis of lesional morphologic features,
      peripheral eosinophilia, and cutaneous histopathologic features, a diagnosis of
      Wells' syndrome was made. Wells' syndrome is extremely rare in childhood, with 27
      pediatric cases reported in the literature. Because it is seen so infrequently,
      there are no specific guidelines for evaluation and management of Wells' syndrome
      among children. The diagnosis should be considered for children with presumed
      cellulitis and eosinophilia who fail to respond to antibiotics. Evaluation should
      include a directed history, physical examination, complete blood count, and stool
      testing for ova and parasites, to identify potential triggers. Treatment is with
      systemic steroid therapy unless disease is limited, in which case medium/high
      potency topical steroids may be indicated. If systemic features are prominent or
      disease is chronic (lasting >6 months), then a referral to hematology/oncology
      should be considered.

PMID- 15995017
TI  - Standard drug concentrations and smart-pump technology reduce continuous
      medication-infusion errors in pediatric patients.
AB  - OBJECTIVE: To determine if combining standard drug concentrations with "smart
      pump" technology reduces reported medication-infusion errors. DESIGN:
      Preintervention and postintervention comparison of reported medication errors
      related to infusion therapies during the calendar years 2002 and 2003. SETTING: A
      242-bed university-affiliated tertiary pediatric hospital. INTERVENTION: Change
      in continuous-medication-infusion process, comprising the adoption of (1)
      standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered
      medication labels. MAIN OUTCOME MEASURES: Comparison of reported continuous
      medication-infusion errors before and after the intervention. RESULTS: The number
      of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8
      per 1000 doses. Preparation errors that occurred in the pharmacy decreased from
      0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased
      from 0.41 to 0.08 per 1000 doses. CONCLUSIONS: The use of standard drug
      concentrations, smart syringe pumps, and user-friendly labels reduces reported
      errors associated with continuous medication infusions. Standard drug
      concentrations can be chosen to allow most neonates to receive needed medications
      without concerns related to excess fluid administration.

PMID- 15995018
TI  - Reasonable suspicion: a study of Pennsylvania pediatricians regarding child
      abuse.
AB  - OBJECTIVE: It has long been assumed that mandated reporting statutes regarding
      child abuse are self-explanatory and that broad consensus exists as to the
      meaning and proper application of reasonable suspicion. However, no systematic
      investigation has examined how mandated reporters interpret and apply the concept
      of reasonable suspicion. The purpose of this study was to identify Pennsylvania
      pediatricians' understanding and interpretation of reasonable suspicion in the
      context of mandated reporting of suspected child abuse. Methodology. An anonymous
      survey was sent (Spring 2004) to all members of the Pennsylvania chapter of the
      American Academy of Pediatrics (n = 2051). Participants were given several
      operational frameworks to elicit their understanding of the concept of reasonable
      suspicion, 2 of which are reported here. Respondents were asked to imagine that
      they had examined a child for an injury that may have been caused by abuse and
      that they had gathered as much information as they felt was possible. They then
      were asked to quantify (in 2 different ways) the degree of likelihood needed for
      suspicion of child abuse to rise to the level of reasonable suspicion. The
      physicians were asked to identify (using a differential-diagnosis framework) how
      high on a rank-order list "abuse" would have to be for it to rise to the level of
      reasonable suspicion (ie, first on the list, second, third, and so on, down to
      tenth). The second framework, estimated probability, used a visual analog scale
      of 0% to 100% to determine how likely suspected abuse would have to be for
      physicians for them to feel that they had reasonable suspicion. That is, would
      they need to feel that there was a 99% likelihood that abuse occurred before they
      felt that they had reasonable suspicion, a 1% likelihood, or something in
      between? In addition to standard demographic features, respondents were queried
      regarding their education on child abuse, education on reasonable suspicion,
      frequency of reporting child abuse, and (self-reported) expertise regarding child
      abuse. The main outcome measures were physician responses on the 2 scales for
      interpreting reasonable suspicion. RESULTS: Pediatricians (n = 1249) completed
      the survey (61% response rate). Their mean age was 43 years; 55% were female; and
      78% were white. Seventy-six percent were board certified, and 65% reported being
      in primary care. There were no remarkable differences in responses based on age,
      gender, expertise with child abuse, frequency of reporting child abuse, or
      practice type. The responses of pediatric residents were indistinguishable from
      experienced physicians, and the responses of primary care pediatricians were no
      different from pediatric subspecialists. Wide variation was found in the
      thresholds that pediatricians set for what constituted reasonable suspicion. On
      the differential-diagnosis scale (DDS), 12% of pediatricians responded that abuse
      would have to rank first or second on the DDS before the possibility rose to the
      level of reasonable suspicion, 41% indicated a rank of third or fourth, and 47%
      reported that a rank anywhere from fifth to as low as tenth still qualified as
      reasonable suspicion. On the estimated-probability scale (EPS), 35% of
      pediatricians responded that for reasonable suspicion to exist, the probability
      of abuse needed to be 10% to 35%. By contrast, 25% of respondents identified a
      40% to 50% probability, 25% stipulated a 60% to 70% probability, and 15% required
      a probability of >or=75%. In comparing individual responses for the 2 scales (ie,
      paired comparisons between each pediatrician's DDS ranking and the estimated
      probability he or she identified), 85% were found to be internally inconsistent.
      To be logically consistent, any score >or=50% on the EPS would need to correspond
      to a DDS ranking of 1; an EPS score of >or=34% would need to correspond with a
      DDS ranking no lower than 2; an EPS score of >or=25% no lower than a DDS ranking
      of 3; and so on. What we found, however, was that pediatricians commonly
      indicated that reasonable suspicion required a 50% to 60% probability that abuse
      occurred, but at the same time, they responded that child abuse could rank as low
      as fourth or fifth on the DDS and still qualify as reasonable suspicion.
      CONCLUSIONS: The majority of states use the term "suspicion" in their mandated
      reporting statutes, and according to legal experts, "reasonable suspicion"
      represents an accurate generalization of most mandated reporting thresholds. Our
      data show significant variability in how pediatricians interpret reasonable
      suspicion, with a range of responses so broad as to question the assumption that
      the threshold for mandated reporting is understood, interpreted, or applied in a
      coherent and consistent manner. If the variability described here proves
      generalizable, it will require rethinking what society can expect from mandated
      reporters and what sort of training will be necessary to warrant those
      expectations.

PMID- 15995019
TI  - Children with idiopathic short stature are poor eaters and have decreased body
      mass index.
AB  - OBJECTIVE: In children with idiopathic short stature (ISS), studies investigating
      body mass index (BMI) or parameters of satiety regulation are scarce, and studies
      analyzing eating behavior are lacking. METHODS: We recruited 214 children (123
      index cases and 91 siblings) with ISS from 123 families. Affected children had to
      have a body height <5th percentile, or, in the case of siblings, the body height
      of 1 child had to be <5th percentile and the other <15th percentile. Medical
      histories were recorded by using structured and standardized interviews. Eating
      behavior was assessed by using the Child Eating Behavior Questionnaire. Percent
      energy intake as fat was assessed by using the Leeds Food Frequency
      Questionnaire. Endocrine markers of body weight regulation (leptin, ghrelin) were
      determined in serum. RESULTS: Compared with population norms, BMI was
      significantly lower (mean: -0.33 standard deviation score). Furthermore, there
      was decreased food responsiveness (mean Child Eating Behavior Questionnaire
      score: 1.9; population mean: 2.4), reduced enjoyment of food (3.2 vs 3.9),
      emotional undereating (2.6 vs 3.0), lower desire to drink (2.0 vs 2.8), and
      increased fussiness over food (3.2 vs 2.9). When the sample was subdivided into
      the 2 groups of "good" and "poor" eaters according to the mothers' assessment of
      the current eating behavior, reduction in BMI as well as the behavioral
      characteristics already delineated in the total sample were found to be even more
      consistent in the subgroup of poor eaters. In the total sample of our children,
      as well as in both subgroups, serum leptin (adjusted for gender, BMI, and Tanner
      stage) was found to be moderately raised but did not differ between poor and good
      eaters. Total serum ghrelin was not different between poor and good eaters.
      CONCLUSIONS: Our clinical, behavioral, and endocrinologic findings in patients
      with ISS point to an altered eating behavior that possibly contributes to their
      short stature.

PMID- 15995020
TI  - Obesity rather than severity of sleep-disordered breathing as the major
      determinant of insulin resistance and altered lipidemia in snoring children.
AB  - OBJECTIVE: Sleep-disordered breathing (SDB) is associated with insulin resistance
      and dyslipidemia in adults and in obese children. However, the prevalence of such
      metabolic abnormalities among snoring children is unknown. This study was done to
      prospectively assess the relative contribution of SDB and obesity to metabolic
      disturbances in a large cohort of snoring children. METHODS: Measurements of
      fasting serum glucose, insulin, and lipids were obtained after polysomnographic
      evaluation in 116 snoring children and in 19 control subjects. Insulin resistance
      was assessed using the insulin/glucose ratio (I/G ratio) and homeostasis model
      assessment (HOMA). RESULTS: A total of 135 children (79 boys; mean age: 8.9 +/-
      3.5 years) were studied. Sixty-four children had moderate to severe SDB (AHI = 5
      per hour of total sleep time [TST]), 52 had mild SDB (AHI = 1 but <5 per hour of
      TST), and 19 were control subjects (AHI <1 per hour of TST). Seventy of these
      children were obese. No significant correlations were found between AHI, lowest
      arterial oxygen saturation, or arousal index and serum insulin, serum glucose,
      I/G ratio, HOMA, or serum lipids for either the whole group or the obese children
      only. However, significant positive correlations were found between I/G ratio and
      relative BMI (relBMI; r = 0.58), HOMA and relBMI (r = 0.52), triglycerides and
      relBMI (r = 0.30), and high-density lipoprotein and relBMI (r = 0.50). No
      significant differences were found in relBMI, I/G ratio, and lipid levels between
      boys and girls. CONCLUSIONS: Among children with suspected SDB, insulin
      resistance and dyslipidemia seem to be determined primarily by the degree of body
      adiposity rather than by the severity of SDB.

PMID- 15995021
TI  - Effects of atomoxetine on growth after 2-year treatment among pediatric patients
      with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Treatment for attention-deficit/hyperactivity disorder is maintained
      typically over periods of months or years and, as a result, the potential effects
      on growth of pharmacotherapy for this disorder have been an area of concern. This
      meta-analysis examined the effect on growth of atomoxetine, now approved in the
      United States for the treatment of attention-deficit/hyperactivity disorder.
      METHODS: Patients (N = 412) were 6 to 16 years of age at the start of the
      treatment period and received atomoxetine treatment (maximal dose: 1.8 mg/kg per
      day) for >or=2 years. Weight and height measurements were analyzed both as actual
      values and after conversion to percentiles and z scores with growth charts from
      the Centers for Disease Control and Prevention. Expected weight and height at the
      end point were calculated through extrapolation from patients' baseline
      percentiles with the growth charts. RESULTS: Results indicated that, after 2
      years, observed weight and height were close to those predicted on the basis of
      the patients' baseline weight and height. Weight increased an average of 10.8 kg,
      a decrease relative to baseline normative weight of 2.7 percentiles,
      corresponding to 0.87 kg. Height increased an average of 13.3 cm, a decrease
      relative to baseline normative heights of 2.2 percentiles, corresponding to 0.44
      cm. For both weight and height, the quartile of patients who were smallest at
      baseline had an increase in end-point percentile, whereas patients in the highest
      quartile had a decrease. CONCLUSIONS: These findings suggested that, at the group
      level, there was only a minimal effect on height after 2 years of treatment with
      atomoxetine and, for patients most at risk (the lowest quartile), there seemed to
      be no effect.

PMID- 15995022
TI  - Factors associated with parental readiness to make changes for overweight
      children.
AB  - OBJECTIVE: The prevalence of childhood obesity is increasing in the United
      States. However, it has been difficult to help children successfully lose weight
      and maintain weight loss. Parental involvement in this effort is important.
      Currently, little is known about parents' readiness to make behavior changes to
      help their children lose weight. The objective of this study was to describe
      demographic factors and parental perceptions associated with parents' readiness
      to make weight-reducing lifestyle changes for their overweight and at-risk-for
      overweight children. METHODS: A total of 151 parents of children who were aged 2
      to 12 years and had BMIs >or=85th percentile for age and gender completed a 43
      item self-administered questionnaire. Parental stage of change, defined as
      precontemplation stage, contemplation stage, and preparation/action stage, was
      determined using an algorithm involving current parental practices and future
      intentions. Parents in the preparation/action stage were considered to be ready
      to make behavior changes to help their child lose weight. Maximum-likelihood
      multinomial logistic regression was used to identify demographics and perceptions
      associated with parental stage of change. RESULTS: Sixty-two percent of the
      children had a BMI >or=95th percentile. Their mean age was 7.5 years, and 53%
      were male. Of the 151 parents, 58 (38%) were in the preparation/action stage of
      change, 26 (17%) were in the contemplation stage, and 67 (44%) were in the
      precontemplation stage. Factors associated with being in the preparation/action
      stage of change were having overweight or older (>or=8 years) children, believing
      that their own weight or child's weight was above average, and perceiving that
      their child's weight was a health problem. After controlling for multiple
      factors, having an older child (odds ratio [OR]: 2.99; 95% confidence interval
      [CI]: 1.18-7.60), believing that they themselves were overweight (OR: 3.45; 95%
      CI: 1.36-8.75), and perceiving that their child's weight was a health problem
      (OR: 9.75; 95% CI: 3.43-27.67) remained significantly associated with being in
      the preparation/action stage of change. CONCLUSIONS: Several demographic factors
      and personal perceptions are associated with a parent's readiness to help his or
      her child lose weight. Knowledge of these factors may be beneficial to providers
      and program developers when addressing pediatric overweight with parents and
      initiating new interventions.

PMID- 15995023
TI  - Structural and functional brain development after hydrocortisone treatment for
      neonatal chronic lung disease.
AB  - OBJECTIVE: There is much concern about potential neurodevelopmental impairment
      after neonatal corticosteroid treatment for chronic lung disease. Dexamethasone
      is the corticosteroid most often used in this clinical setting, and it has been
      shown to impair cortical growth among preterm infants. This study evaluated long
      term effects of prematurity itself and of neonatal hydrocortisone treatment on
      structural and functional brain development using three-dimensional MRI with
      advanced image-processing and neurocognitive assessments. METHODS: Sixty children
      born preterm, including 25 children treated with hydrocortisone and 35 children
      not treated with hydrocortisone, and 21 children born at term were evaluated, at
      a mean age of 8 years, with quantitative MRI and neurocognitive assessments
      (Wechsler Intelligence Scales for Children-Revised [WISC-R]). Automatic image
      segmentation was used to determine the tissue volumes of cerebral gray matter,
      white matter, and cerebrospinal fluid. In addition, the volume of the hippocampus
      was determined manually. WISC-R scores were recorded as mean intelligence scores
      at evaluation. Neonatal hydrocortisone treatment for chronic lung disease
      consisted of a starting dose of 5 mg/kg per day tapered over a minimum of 3
      weeks. RESULTS: Cerebral gray matter volume was reduced among preterm children
      (regardless of hydrocortisone treatment), compared with children born at term
      (preterm: 649 +/- 4.4 mL; term: 666 +/- 7.3 mL). Birth weight was shown to
      correlate with gray matter volume at 8 years of age in the preterm group (r =
      0.421). Cerebrospinal fluid volume was increased among children born preterm,
      compared with children born at term (preterm: 228 +/- 4.9 mL; term: 206 +/- 8.2
      mL). Total hippocampal volume tended to be lower among children born preterm,
      with a more pronounced reduction of hippocampal volume among boys (preterm: 6.1
      +/- 0.13 mL; term: 6.56 +/- 0.2 mL). The WISC-R score was lower for children born
      preterm, compared with children born at term (preterm: 99.4 +/- 12.4; term: 109.6
      +/- 8.8). Children treated with neonatal hydrocortisone had very similar volumes
      of gray matter (preterm with hydrocortisone: 650 +/- 7.0 mL; preterm without
      hydrocortisone: 640 +/- 5.6 mL), white matter (preterm with hydrocortisone: 503
      +/- 6.1 mL; preterm without hydrocortisone: 510 +/- 4.9 mL), and cerebrospinal
      fluid (preterm with hydrocortisone: 227 +/- 7.4 mL; preterm without
      hydrocortisone: 224 +/- 6.0 mL), compared with untreated infants. The hippocampal
      volumes were similar in the 2 groups (preterm with hydrocortisone: 5.92 +/- 0.15
      mL; preterm without hydrocortisone: 5.81 +/- 0.12 mL). The WISC-R score
      assessments were within the normal range for both groups, with no difference
      between the groups (preterm with hydrocortisone: 100.8 +/- 13; preterm without
      hydrocortisone: 98.6 +/- 12.3). CONCLUSIONS: Prematurity is associated with mild
      brain structural differences that persist at 8 years of age, with associated
      lower scores in neurocognitive assessments. The data suggest that perinatal
      hydrocortisone given at the described dosage has no long-term effects on either
      neurostructural brain development or neurocognitive outcomes.

PMID- 15995024
TI  - Intravenously administered immunoglobulin in the treatment of childhood Guillain
      Barre syndrome: a randomized trial.
AB  - OBJECTIVE: To determine the optimal treatment for childhood Guillain-Barre
      syndrome (GBS). METHODS: We performed a randomized, multicenter study of GBS
      according to international diagnostic criteria. In study 1 (early treatment),
      children able to walk unaided for 5 meters were randomized for 1 g/kg
      intravenously administered immunoglobulin (IVIG) over 2 days or no treatment. The
      primary outcome measure was the degree of disability at nadir. In study 2
      (treatment for severe GBS), children unable to walk 5 meters unaided were
      randomized for 1 g/kg IVIG over 2 days or 0.4 g/kg IVIG over 5 days. The primary
      outcome measure was the number of days needed to regain the ability to walk
      unaided. Children randomized for no treatment in study 1 could enter study 2 if
      loss of unaided walking occurred. RESULTS: Ninety-five children with GBS were
      registered in 40 months. Twenty-one children were randomized in study 1 and 51 in
      study 2 (5 after deterioration in study 1). Twenty-eight children were not
      randomized for various reasons. Eleven of 21 patients in study 1 lost the ability
      to walk unassisted and 6 were bedridden, with no statistically significant
      difference between the children initially randomized for treatment versus no
      treatment. Recovery occurred faster in the group randomized for early treatment.
      In study 2, recovery did not differ significantly between the children treated
      for 2 days versus 5 days (median time to unaided walking: 19 days vs 13 days).
      Secondary transient deterioration in the disability score occurred more
      frequently in the group with the 2-day regimen than in the group treated for 5
      days (5 of 23 patients vs 0 of 23 patients). Multivariate analysis with Cox
      regression showed that disease severity at the nadir was the only prognostic
      factor for recovery. CONCLUSIONS: Treatment with IVIG before loss of unaided
      walking did not give rise to a less severe course, but recovery occurred somewhat
      faster. However, given the small number of patients, the power of this conclusion
      is low. For treatment after loss of unaided walking, there was no significant
      difference in the effectiveness of 2 g/kg IVIG administered over 2 days versus 5
      days. Early "relapses" occurred more frequently after the shorter treatment
      regimen.

PMID- 15995025
TI  - The incidence and course of retinopathy of prematurity: findings from the early
      treatment for retinopathy of prematurity study.
AB  - OBJECTIVES: To estimate the incidence of retinopathy of prematurity (ROP) in the
      Early Treatment for Retinopathy of Prematurity (ETROP) Study and compare these
      results with those reported in the Cryotherapy for Retinopathy of Prematurity
      (CRYO-ROP) Study. METHODS: The ETROP Study, as part of its protocol, screened
      6998 infants at 26 centers throughout the United States. Serial eye examinations
      were conducted for infants born weighing <1251 g, making it possible to estimate
      the frequency of ROP in different birth weight and gestational age categories.
      ROP was categorized according to the International Classification for ROP.
      RESULTS: The incidence of any ROP was 68% among infants of <1251 g. The findings
      were compared with those for infants born in 1986 and 1987 in the CRYO-ROP Study.
      The overall incidences of ROP were similar in the 2 studies, but there was more
      zone I ROP in the ETROP Study. Among infants with ROP, more-severe ROP
      (prethreshold) occurred for 36.9% of infants in the ETROP Study and 27.1% of
      infants in the CRYO-ROP Study. The gestational age of onset of ROP of different
      severities has changed very little since the CRYO-ROP Study was conducted.
      CONCLUSIONS: ROP remains a common important problem among infants with birth
      weights of <1251 g. The incidence of ROP, time of onset, rate of progression, and
      time of onset of prethreshold disease have changed little since the CRYO-ROP
      natural-history study.

PMID- 15995026
TI  - Will I be alive in 2005? Adolescent level of involvement in risk behaviors and
      belief in near-future death.
AB  - OBJECTIVE: We examined the association between a belief in one's future mortality
      and various risk-taking behaviors among urban black adolescents. In particular,
      we investigated whether adolescents with higher levels of participation in
      various risk behaviors were more likely to believe in their future death as
      compared with adolescents with lesser levels of risk-taking behavior. METHODS:
      Data obtained from April 1994 to March 1997 were analyzed for a total of 2694
      adolescents, aged 12 to 21 years. The odds of believing that one would die within
      the next 2 years were calculated for various levels of participation in risk
      behaviors involving alcohol, drugs, and criminal or violent acts. RESULTS: A
      total of 160 adolescents (7.1% of all boys and 5.4% of all girls) reported that
      they believed that they would die within the next 2 years. The adjusted odds of
      future death belief among adolescents who both actively engaged in and knew
      others who participated in all of the various risk behaviors, relative to
      adolescents who neither personally engaged in nor knew others who participated in
      any of the risk behaviors, was 3.22 (95% confidence interval [CI]: 2.01-5.17) vs
      1.14 (95% CI: 0.67-1.95) for drug use and drug selling, 2.01 (95% CI: 1.38-2.92)
      vs 0.8 (95% CI: 0.39-1.62) for combined alcohol and drug use, and 5.60 (95% CI:
      2.03-15.47) vs 1.61 (95% CI: 1.08-2.42) for violent physical behavior. In
      addition, residence in a foster home was significantly associated with death
      belief after adjustment for all other variables. CONCLUSIONS: There is a
      significant relationship between certain risk behaviors and belief in near-future
      death. Moreover, higher levels of involvement in risk behaviors were associated
      with a stronger likelihood of belief in near-future mortality. Identification of
      adolescents who engage in certain risky behaviors, combined with a recognition of
      the degree to which the adolescent participates in the particular behavior(s),
      may be used to facilitate more rapid intervention among youths who either believe
      in their imminent demise or engage in behaviors that increase the likelihood of
      their untimely death.

PMID- 15995027
TI  - Part-time residency in pediatrics: description of current practice.
AB  - OBJECTIVE: To determine current national utilization levels of part-time
      pediatric residency and to identify reasons for pursuing training on a part-time
      basis. DESIGN: Data were obtained through (1) a survey regarding part-time
      residency mailed to all accredited pediatric residency programs, (2) the American
      Medical Association Fellowship and Residency Interactive Electronic Database, and
      (3) the American Academy of Pediatrics postgraduate level 3 survey, 2003.
      RESULTS: Of the 190 accredited pediatric residency programs surveyed, 156 (82%)
      responded; 18 (12%) of these programs had >or=1 part-time resident during
      academic years 2000-2003. Nationally, 43 of 6609 residents represented in the
      survey (0.7%) undertook some of their training on a part-time basis. All programs
      prorated salaries in proportion to time percentage, 10 (71%) continued full
      benefits for part-time residents, and 15 (88%) used a reduced call schedule.
      Although multiple reasons were given for part-time status, including travel
      (16%), research (14%), advanced degrees (9%), personal illness (9%), and family
      illness (5%), 67% cited child care as 1 reason. Length of residency was extended
      by an average of 15 months (range: 4-36 months). Analysis of the American Medical
      Association Fellowship and Residency Interactive Electronic Database showed that
      45 (24%) of 190 programs advertise part-time slots. CONCLUSIONS: Although
      numerous pediatric programs advertise part-time positions, few residents actually
      held such positions during a 3-year period. There is variability among programs
      in how benefits and call schedules are managed. Part-time positions are chosen
      for multiple reasons, but the most common reason is to care for children.
      Pediatric residency programs can use this information to meet resident needs.

PMID- 15995028
TI  - Increased expression of urinary matrix metalloproteinases parallels the extent
      and activity of vascular anomalies.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) and the angiogenic proteins basic
      fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)
      have been implicated in mechanisms of human cancer and metastasis. Assays were
      conducted on the urine of patients with vascular anomalies (tumors and
      malformations), relatively common and occasionally life-threatening disorders for
      which few therapies exist. We sought to determine whether these angiogenesis
      modulators are present in the urine and whether their expression is associated
      with the extent and clinical course of the vascular lesion. METHODS: A total of
      217 patients with vascular anomalies and 74 age-matched control subjects
      participated. Urinary MMP expression was determined by substrate gel
      electrophoresis. Urinary bFGF and VEGF levels were measured by enzyme-linked
      immunosorbent assay. Each patient was assigned to 1 of 2 categories (tumor or
      malformation) and 1 of 9 specific groups. Extent of the vascular lesion and
      activity were scored by a blinded clinician. RESULTS: Urinary high molecular
      weight (hMW) MMPs and bFGF were significantly increased in patients with vascular
      tumors (53%) and vascular malformations (41%), compared with control subjects
      (22%). These percentages increased as a function of extent of the lesion and
      disease activity. hMW MMPs were increased in 4 groups: infantile hemangioma,
      other vascular neoplasms, lymphatic malformation and capillary-lymphaticovenous
      malformations, and extensive and unremitting capillary malformation and
      arteriovenous malformation. No significant differences among the groups were
      detected for low molecular weight MMPs or VEGF. CONCLUSIONS: Expression patterns
      of hMW MMPs and bFGF in the urine of patients with tumors and malformations are
      consistent with their different clinical behavior. These data represent the first
      evidence that MMPs are elevated in the urine of children with vascular anomalies.
      These data also suggest that the increased expression of urinary MMPs parallels
      the extent and activity of vascular anomalies in children. In addition to tumors,
      vascular malformations are angiogenesis dependent, suggesting that progression of
      a vascular malformation might be suppressed by angiogenic inhibitors, which would
      target bFGF and MMPs.

PMID- 15995029
TI  - The epidemiology of recurrent abdominal pain from 2 to 6 years of age: results of
      a large, population-based study.
AB  - OBJECTIVE: Recurrent abdominal pain (RAP) is one of the most common complaints of
      childhood and is associated with several adverse outcomes in adulthood. Few
      large, population-based, longitudinal studies have been conducted. The purpose of
      this study was to investigate the prevalence and epidemiologic features of RAP
      through early childhood. DESIGN: We report findings from a large, population
      based, cohort study of childhood (the Avon Longitudinal Study of Parents And
      Children). The prevalence and continuity of RAP from 2 to 6 years of age were
      explored, with associated physical and psychological symptoms among the children
      and their parents. RESULTS: In a population cohort of 13971 children, RAP was
      reported for 11.8% of 6-year-old children. It was less common at ages 2 years
      (3.8%) and 3 years (6.9%). There was a striking degree of continuity of RAP
      between the ages of 2 and 6 years. RAP was associated with headaches and limb
      pains among children and with higher rates of anxiety among both children
      (adjusted odds ratio: 2.12; 95% confidence interval: 1.70-2.65) and their mothers
      (odds ratio: 1.75; 95% confidence interval: 1.30-2.36). CONCLUSIONS: In a large,
      population-based, cohort study, RAP was found to be increasingly common up to the
      age of 6 years. Children with RAP at a young age have a high risk of RAP later in
      childhood. RAP is associated with other somatic pain symptoms among children and
      with symptoms of anxiety among children and their mothers. These findings
      highlight the high prevalence and continuity of RAP through early childhood and
      the importance of considering psychological symptoms for these children and their
      families.

PMID- 15995030
TI  - Croup hospitalizations in Ontario: a 14-year time-series analysis.
AB  - OBJECTIVE: Croup is the most common form of airway obstruction in children. Known
      to be primarily viral, the seasonality of croup has been examined largely through
      its association with the human parainfluenza viruses. This study examined the
      seasonal pattern of croup hospitalizations in relation to age and gender for the
      province of Ontario during a 14-year period. METHODS: A retrospective, population
      based study design was used to examine seasonal and temporal patterns of croup
      hospitalizations from April 1, 1988, to March 31, 2002. All residents of Ontario
      who were aged 0 to 4 years and eligible for universal health coverage during the
      study period were included for analysis. Time-series analyses then were conducted
      on monthly aggregations of hospitalizations. RESULTS: This study found strong
      evidence of croup hospitalization seasonality, with a biennial midautumn peak and
      annual summer trough, evident throughout the 14-year study period (Fisher's kappa
      = 51.11; Bartlett Kolmogorov Smirnov = 0.552). The pattern was observed in all
      children aged 0 to 4, although boys were hospitalized 2 times more often than
      girls of the same age. Rates of croup hospitalization were lower for children
      aged 1 to 4 years than for children aged 0 to <1. A marked decrease in croup
      hospitalizations was observed after the winter of 1993/1994 and continued to
      decrease in a step-wise manner for the remainder of the study period.
      CONCLUSIONS: This study delineates a clear biennial pattern of seasonal croup
      hospitalizations, varying by age and gender, with a large decrease in
      hospitalizations after the winter of 1993/1994. It is expected that these
      findings will have important implications for the treatment and management of
      childhood croup.

PMID- 15995031
TI  - Association between streptococcal infection and obsessive-compulsive disorder,
      Tourette's syndrome, and tic disorder.
AB  - OBJECTIVE: Reports have suggested that streptococcal infection may be
      etiologically related to pediatric autoimmune neuropsychiatric disorders
      (PANDAS), but there are few good epidemiologic studies to support this theory.
      Using population-based data from a large West-Coast health maintenance
      organization, we assessed whether streptococcal infection was associated with
      increased risk for obsessive-compulsive disorder (OCD), Tourette's syndrome (TS),
      or tic disorder. METHODS: This is a case-control study of children 4 to 13 years
      old receiving their first diagnosis of OCD, TS, or tic disorder between January
      1992 and December 1999 at Group Health Cooperative outpatient facilities. Cases
      were matched to controls by birth date, gender, primary physician, and propensity
      to seek health care. RESULTS: Patients with OCD, TS, or tic disorder were more
      likely than controls to have had prior streptococcal infection (OR: 2.22; 95% CI:
      1.05, 4.69) in the 3 months before onset date. The risk was higher among children
      with multiple streptococcal infections within 12 months (OR: 3.10; 95% CI: 1.77,
      8.96). Having multiple infections with group A beta-hemolytic streptococcus
      within a 12-month period was associated with an increased risk for TS (OR: 13.6;
      95% CI: 1.93, 51.0). These associations did not change appreciably when limited
      to cases with a clear date of onset of symptoms or with tighter matching on
      health care behavior. CONCLUSION: These findings lend epidemiologic evidence that
      PANDAS may arise as a result of a postinfectious autoimmune phenomenon induced by
      childhood streptococcal infection.

PMID- 15995032
TI  - Frequency of fungemia in hospitalized pediatric inpatients over 11 years at a
      tertiary care institution.
AB  - OBJECTIVES: To determine the frequency of bloodstream fungal infections in
      children who were admitted to our tertiary institution over an 11-year period.
      METHODS: We conducted a retrospective cohort study of patients who were aged 0 to
      21 years, had bloodstream fungal infections, and were admitted to the University
      of California, Los Angeles from 1991 through 2001. Patients were identified
      through the microbiology laboratory database. All positive fungal cultures for
      pediatric inpatients were reviewed. For each fungemic patient, a review of
      clinical course, cause, and outcome was performed. RESULTS: Over 11 years, 1124
      pediatric inpatients with 3633 positive cultures had evidence of fungal
      colonization or infection. The mean incidence of positive fungal cultures
      increased from 105 between 1991 and 1996 to 129 patients per year between 1997
      and 2001. Fungal isolates were mainly Candida species (85%) obtained primarily
      from respiratory (41%) and urine (27%) cultures. Only 7.5% of positive fungal
      cultures were from blood, although 24490 pediatric admissions prompted 72960
      bacterial and fungal blood cultures, at charges of 2.52 million dollars. Of 14592
      fungal blood cultures, <2% (n = 272) were positive, involving <1% (n = 97) of
      patients. The mean rise in number of children with fungemia was significant, from
      6.8 between 1991 and 1996 to 13.0 patients per year between 1997 and 2001.
      Fungemia was associated with a high all-cause mortality rate (46%), particularly
      in immunocompromised patients (57%). Organisms recovered were primarily Candida
      species (91%). There was a decline in C albicans and C glabrata fungemia and an
      increase in C parapsilosis organisms. In 84% of patients, fungal organisms were
      isolated from both bacterial and fungal blood cultures, and in 74%, the same
      organism was isolated from additional body sites. CONCLUSIONS: Episodes of
      fungemia increased significantly over 11 years as compared with a moderate
      increase in positive fungal cultures and were associated with high all-cause
      mortality rates. More sensitive assays for early identification of fungal
      bloodstream infections are warranted.

PMID- 15995033
TI  - Effect of nutrition on growth in short stature before and during growth-hormone
      therapy.
AB  - OBJECTIVE: Although nutritional counseling is an integral part of the management
      of rapidly growing children, few studies have focused on the importance of
      nutritional supervision during growth-hormone (GH) therapy. The objective of this
      study was to study the effect of caloric intake on growth before and during GH
      therapy. METHODS: A total of 115 short normal prepubertal children who were 7.4
      +/- 1.2 years of age (mean +/- SD) and had height SD score (SDS) of -2.5 +/- 0.6
      were treated with a GH dose range of 0.13 to 0.52 mg/kg per week for 1 year. A 3
      day nutritional recall and blood chemistry analysis were repeated every 3 months.
      RESULTS: Caloric intake (expressed as % recommended dietary allowance) was
      positively correlated with the pretreatment growth velocity (SDS) and the
      increment in growth velocity SDS during the first year of GH therapy (r = 0.363
      and 0.493). By stepwise regression analysis, we identified 4 parameters that
      could predict the 1-year increment in growth velocity SDS: the contribution of
      each factor (% variability) was pretreatment growth velocity SDS 36%, GH dose
      (27%), caloric intake 4%, and the integrated concentration of GH 2% (r(2) =
      0.689). GH therapy induced an alkaline phosphatase increment of 59 +/- 49 IU/mL,
      an insulin-like growth factor-I increment of 32.6 +/- 11.9 nmol/L, and a GH
      binding protein increment of 10.2 +/- 2.7%. During GH therapy, an increase in
      serum transferrin (56.5 +/- 35.2 mg/dL) and a decrease in serum iron (20.5.5 +/-
      20.2 microg/dL) were noted. These changes could not be detected through
      hemoglobin levels or hematopoietic indexes. Dietary iron supplementation reversed
      this phenomenon. CONCLUSIONS: The nutritional status of GH-treated patients
      before and throughout the course of GH treatment should be monitored closely to
      improve the growth response and prevent nutritional deficiencies. Special
      emphasis should be placed on iron nurture.

PMID- 15995034
TI  - Children's residential weight-loss programs can work: a prospective cohort study
      of short-term outcomes for overweight and obese children.
AB  - OBJECTIVE: The evidence base for child obesity treatment is weak. Children's
      weight-loss camps, despite their popularity, have not been properly evaluated.
      This study evaluated the effectiveness of a residential weight-loss camp program
      for overweight and obese children. METHODS: A total of 185 overweight children
      (mean age: 13.9 years) enrolled in 1 of 4 consecutive programs between 1999 and
      2002 (intervention group) were compared with 94 children of similar ages who were
      not camp attendees, ie, 38 overweight children and 56 normal-weight children. The
      intervention group attended a 6-week (maximum) summer residential weight-loss
      camp. The program included a daily schedule of six 1-hour, skill-based, fun,
      physical activity sessions, moderate dietary restriction, and group-based
      educational sessions. All children were assessed for body weight, height, and
      other anthropometric measures, blood pressure, aerobic fitness, self-esteem, and
      selected sports skills. RESULTS: Campers, who stayed for a mean of 29 days, lost
      6.0 kg, reduced their BMI by 2.4 units, and reduced their BMI SD scores by 0.28.
      Fat mass decreased significantly (from 42.7 to 37.1 kg), whereas fat-free mass
      did not change. In contrast, both comparison groups gained weight during this
      period. Camp attendees also showed significant improvements in blood pressure,
      aerobic fitness, and self-esteem. Longer durations of stay were associated with
      greater improvements in outcomes. CONCLUSIONS: In the short term at least, this
      weight-loss program was effective across a range of health outcomes. Ongoing
      research is examining the maintenance of these improvements. Future research
      should investigate whether benefits can be generalized across weight-loss camps
      and how the intervention can be adapted to nonresidential, term-time settings.

PMID- 15995035
TI  - Adverse health consequences that co-occur with depression: a longitudinal study
      of black adolescent females.
AB  - OBJECTIVE: The purpose of this study was to identify adverse health consequences
      that may co-occur with depression among black female adolescents. METHODS:
      Adolescents were recruited from high-risk neighborhoods in Birmingham, Alabama.
      The sample comprised 460 black female adolescents (aged 14-18 years) who
      completed assessments at baseline and at 6 and 12 months. Only adolescents who
      consistently scored above the threshold for depression at all 3 assessments (n =
      76) or below the threshold at all 3 assessments (n = 174) were included (N = 250)
      in the data analysis. Within this sample, adolescents who were depressed were
      compared with those who were not depressed with respect to the following health
      consequences: low self-esteem, emotional abuse, physical abuse, verbal abuse,
      poor body image, and antisocial behavior. RESULTS: Using generalized estimating
      equations and controlling for covariates, depressed adolescents were 5.3 times
      more likely to report low self-esteem, 4.3 times more likely to report emotional
      abuse, 3.7 times more likely to report being physically abused, and almost 3
      times as likely to report being verbally abused. Furthermore, depressed
      adolescents were more than twice as likely to report poor body image and nearly
      twice as likely to report engaging in antisocial behaviors. CONCLUSIONS: The
      findings suggest that a broad range of adverse health consequences may accompany
      depression among black female adolescents. Physicians need to be alert to the co
      occurrence of depression and low self-esteem; emotional, physical, and verbal
      abuse; poor body image; and antisocial behaviors among this population.

PMID- 15995036
TI  - Open access in primary care: results of a North Carolina pilot project.
AB  - OBJECTIVE: Appointment delays impede access to primary health care. By reducing
      appointment delays, open access (OA) scheduling may improve access to and the
      quality of primary health care. The objective of this pilot study was to assess
      the potential impact of OA on practice and patient outcomes by using pilot-study
      data from 4 North Carolina primary care practices. METHODS: We conducted an
      interrupted time-series pilot study of 4 North Carolina primary care practices (2
      family medicine and 2 pediatric practices) participating in a quality-improvement
      (QI) collaborative from May 2001 to May 2002. The year-long collaborative
      comprised 25 practices and consisted of three 2-day meetings led by expert
      faculty, monthly data feedback, and monthly conference calls. Our main outcome
      measures were appointment delays, appointment no-shows, patient satisfaction,
      continuity of care, and staff satisfaction during the 12-month study period.
      RESULTS: Providers in all 4 practices successfully implemented OA. On average,
      providers reduced their delay to the third available preventive care appointment
      from 36 to 4 days. No-show rates declined (first quarter [Q1] rate: 16%; fourth
      quarter [Q4] rate: 11%; no-show reduction: 5% [95% confidence interval: 1%,
      10%]), and overall patient satisfaction improved (Q1: 45% rated overall visit
      quality as excellent; Q4: 61% rated overall visit quality as excellent; change in
      satisfaction: 16% [95% confidence interval: 0.2%, 30%]). Continuity of care
      followed a similar pattern of improvement, but the change was not statistically
      significant. Staff satisfaction neither improved nor declined. CONCLUSIONS: This
      pilot study suggests that primary care practices can implement OA successfully by
      using QI-collaborative methods. These results provide preliminary evidence that
      OA may improve practice and patient outcomes in primary care. These analyses
      should be repeated in larger groups of practices with longer follow-up.

PMID- 15995037
TI  - Uninsurance and health care access among young adults in the United States.
AB  - OBJECTIVE: Young adults who are 19 to 24 years of age are the most likely age
      group to be uninsured in the United States, yet little is known about how
      uninsurance might affect health care access among young adults. The objective of
      this study was to describe the association between health insurance status and
      health care access among young adults while controlling for other determinants of
      access to care. METHODS: We conducted a cross-sectional analysis of data from
      11,866 19- to 24-year-old respondents who completed the National Health Interview
      Survey between 1998 and 2001. We present percentages and adjusted relative risk
      of young adults who in the previous year delayed or missed medical care because
      of cost, did not fill a prescription because of cost, had not spoken to a health
      professional, or identified no usual source of health care. RESULTS: Among the
      young adults studied, 27% of women and 33% of men were uninsured. After potential
      confounders were adjusted for, the uninsured remained at significantly higher
      risk for reporting delayed or missed medical care (women: adjusted relative risk
      [95% confidence interval]: 3.24 [2.72-3.82]; men: 4.31 [3.44-5.34]), not filling
      a prescription because of cost (women: 3.27 [2.55-4.16]; men: 4.05 [2.78-5.81]),
      having no contact with a health professional (women: 2.54 [2.01-3.09]; men: 1.60
      [1.43-1.77]), and having no usual source of health care (women: 3.45 [3.05-3.90];
      men: 2.27 [2.06-2.48]) relative to privately insured peers. Women with Medicaid
      did not differ significantly from privately insured women in these measures.
      CONCLUSIONS: Uninsured young adults were significantly more likely than privately
      insured peers to report barriers to obtaining needed care, having no contact with
      a health professional, and identifying no usual source of health care. Given the
      high rates of uninsurance among young adults, additional study is needed to
      examine how these barriers affect the immediate and future health of the young
      adult.

PMID- 15995038
TI  - Comparison of minitrampoline- and full-sized trampoline-related injuries in the
      United States, 1990-2002.
AB  - OBJECTIVE: To compare mini- and full-sized trampoline-related injuries in the
      United States. METHODS: A retrospective analysis of data was conducted for all
      ages from the National Electronic Injury Surveillance System (NEISS) of the US
      Consumer Product Safety Commission from 1990 to 2002. We compared 137
      minitrampoline-related injuries with 143 full-sized trampoline-related injuries,
      randomly selected from all full-sized trampoline-related injuries reported to the
      NEISS during the study period. RESULTS: Patients ranged in age from 1 to 80 years
      (mean [SD]: 13.9 [17.7]) and 2 to 52 years (mean [SD]: 11.0 [8.0]) for mini- and
      full-sized trampoline-related injuries, respectively. Most patients were younger
      than 18 years (82% mini, 91% full-sized). Thirty-two percent of minitrampoline-
      and 19% of full-sized trampoline-related injuries were to children who were
      younger than 6 years; girls predominated (63% mini, 51% full-sized). Children who
      were younger than 6 years were more likely to be injured on a minitrampoline than
      on a full-sized trampoline, when compared with 6- to 17-year-olds (odds ratio
      [OR]: 2.43; 95% confidence interval [CI]: 1.33-4.47). The majority of injuries
      occurred at home (87% mini, 89% full-sized). All patients who were injured on a
      minitrampoline were treated and released, whereas 5% of patients who were injured
      on a full-sized trampoline were admitted to the hospital. On minitrampolines,
      children who were younger than 6 years were at risk for head lacerations (OR:
      4.98; 95% CI: 1.71-16.03), and children who were 6 to 17 years were at risk for
      lower extremity strains or sprains (OR: 6.26; 95% CI: 1.35-59.14). Children who
      were 6 to 17 years and injured on a full-sized trampoline were at risk for lower
      extremity strains or sprains (OR: 4.85; 95% CI: 1.09-44.93). Lower extremity
      strains or sprains were the most common injury sustained by adults (18 years and
      older; 33% mini, 15% full-sized). CONCLUSIONS: Injury patterns were similar for
      mini- and full-sized trampolines, although minitrampoline-related injuries were
      less likely to require admission to the hospital and more commonly resulted in
      head lacerations among children who were younger than 6 years. Risk for injury
      could not be determined because of the lack of data regarding duration of
      exposure to risk. We therefore conclude that the use of full-sized trampolines by
      children should follow the policy recommendations of the American Academy of
      Pediatrics. Trampolines, including minitrampolines, should be regarded as
      training devices and not as toys. Until more data are available regarding
      exposure to risk, we caution against the use of the minitrampoline as a play
      device by children in the home, which is where most minitrampoline-related
      injuries occur.

PMID- 15995039
TI  - Comparison of mothers' and counselors' perceptions of predelivery counseling for
      extremely premature infants.
AB  - OBJECTIVE: To understand mothers' and counselors' perceptions of their roles in
      decision-making about resuscitation of extremely premature infants at delivery
      and to assess mothers' and counselors' satisfaction with the counseling and
      decision-making process. METHODS: Mothers who delivered an infant between 22 and
      27 completed weeks of gestation and their self-identified counselor were
      interviewed using a structured interview format. Mothers' and counselors'
      perceptions of the content, tone, and directiveness of predelivery counseling and
      their satisfaction with the decision-making process were compared. Demographic
      data were collected for the mothers, infants, and counselors. Simple descriptive
      statistics described demographic characteristics of mothers, counselors, and
      infants. Pearson's correlation coefficient was used to determine agreement within
      individual mother-counselor pairs about the content and directiveness of
      counseling. RESULTS: Thirty-three counselors and 15 mother-counselor pairs were
      interviewed. The majority (66.7%) of mothers stated that the counselor had made a
      treatment recommendation, and 60% stated that they had no choice in how their
      infant would be treated. Only 27.3% of counselors stated that they had made a
      recommendation, saying instead that they had described the treatment plan or
      offered options. Counselors believed that mothers were given a treatment choice
      in 57.6% of encounters. Specific mother-counselor pairs showed little correlation
      in their perceptions of whether a treatment recommendation had been made (R =
      0.0) or a choice had been given about resuscitation (R = 0.07). Despite a lack of
      perceived choice, mothers generally believed that they were included in treatment
      decisions (66.7%) and were satisfied with the amount of influence that they had
      in the decision-making process (73.3%). CONCLUSIONS: The decision-making process
      in this study conforms most closely to a model of informed assent. Mothers may
      have been satisfied with this type of counseling because they felt informed and
      included in the decision-making process. Physicians and nurses need to elicit
      mothers' preferences to incorporate them into the treatment plan, as counseling
      about the resuscitation of extremely premature infants at delivery is considered
      directive by mothers even when it is not intended to be directive.

PMID- 15995040
TI  - Screening and counseling associated with obesity diagnosis in a national survey
      of ambulatory pediatric visits.
AB  - OBJECTIVE: To examine clinician-reported diagnosis of obesity and frequency of
      blood pressure assessment and diet and exercise counseling during ambulatory
      visits made by children and adolescents. METHODS: The National Ambulatory Medical
      Care Survey and National Hospital Ambulatory Medical Care Survey 1997 to 2000
      were combined for visits to clinicians of 2- to 18-year-olds. Well-child visits
      (WCVs) were examined for frequencies of obesity diagnosis, blood pressure
      screening, and diet and exercise counseling in relation to patient and clinician
      characteristics. Multivariate models examined the relationship of patient and
      visit characteristics with diet and exercise counseling. RESULTS: Of the 32 930
      ambulatory visits made by 2- to 18-year-olds in 1997-2000, obesity was diagnosed
      at 0.78% of all visits and 0.93% of WCVs. Blood pressure assessment was reported
      in 61.1% of WCVs with obesity diagnosis compared with 43.9% of WCVs without
      obesity diagnosis. WCVs with obesity diagnosis had higher diet counseling rates
      (88.4% vs 35.7%) and higher exercise counseling rates (69.2% vs 18.6%). Diet
      counseling was reported for 88.4% and exercise counseling was reported for 69.2%
      of visits with an obesity diagnosis compared with 35.7% and 18.6% during WCVs
      without a diagnosis of obesity. In multivariate analyses, factors associated with
      diet counseling at WCVs were diagnosis of obesity (odds ratio [OR]: 12.9; 95%
      confidence interval [CI]: 3.0-55.3), being seen by pediatricians (OR: 2.5; 95%
      CI: 1.6-3.9), 2- to 5-year-olds compared with 12- to 18-year-olds (OR: 0.7; 95%
      CI: 0.5-1.0), and self-pay compared with private insurance visits (OR: 0.6; 95%
      CI: 0.4-0.9). Associations with exercise counseling were similar to those for
      diet counseling, but exercise counseling occurred less frequently in visits by
      black youths compared with white youths (OR: 0.5; 95% CI: 0.3-0.8). CONCLUSIONS:
      Clinicians may overlook obesity during WCVs. Programs to increase obesity
      diagnosis could improve diet and exercise counseling rates, but even with
      diagnosis of obesity, significant opportunities for screening and intervention
      are missed.

PMID- 15995041
TI  - Modeling clinical outcome of children with autistic spectrum disorders.
AB  - OBJECTIVES: Autistic spectrum disorders (ASD) have variable developmental
      outcomes, for reasons that are not entirely clear. The objective of this study
      was to test the clinical observation that initial developmental parameters
      (degree of atypicality and level of intelligence) are a major predictor of
      outcome in children with ASD and to develop a statistical method for modeling
      outcome on the basis of these parameters. METHODS: A retrospective chart review
      was conducted of a child development program at a tertiary center for the
      evaluation of children with developmental disabilities. All children who had ASD,
      were seen by J.C. between July 1997 and December 2002, met Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for
      autism or pervasive developmental disorder (referred to hereafter as ASD), had
      undergone at least 1 administration of the Childhood Autism Rating Scale (CARS),
      and had at least 1 determination of developmental quotient (DQ) or IQ (N = 91)
      were studied. The sample was 92.3% male and 80.2% white. METHODS: The DSM-IV was
      used to confirm that each patient met criteria for a diagnosis of autism or
      pervasive developmental disorder. The CARS was used to quantify the severity of
      expression of ASD. Age at evaluation, CARS score, and DQ or IQ at each visit were
      extracted from the medical record. The 2 independent sample t test or the Mann
      Whitney test was used for comparing CARS and age between 2 groups: first recorded
      DQ or IQ <0.70 (n = 58) versus first recorded DQ or IQ >or=0.70 (n = 33).
      Associations among CARS score, IQ or DQ, and age were examined using Pearson or
      Spearman correlation. A mixed-effect model was used for expressing the
      multivariate model. Length of follow-up (period) was calculated by subtracting
      age in months at initial evaluation from age in months at each follow-up
      evaluation. Therefore, at first evaluation, period = 0. Period was considered as
      a random effect because collection of repeated information from patients was not
      uniform. The predictive relationships among CARS, age at first evaluation,
      period, and DQ or IQ group (<0.70 and >or=0.70) were examined using a mixed
      effects model. Variables that were expressed as percentage change between first
      and last measurements were analyzed using the t test or the Mann-Whitney test.
      Socioeconomic status was assessed using Hollingshead criteria. RESULTS: All
      patients met DSM-IV criteria for ASD. Mean age at initial evaluation was 46.2
      months (SD: 23.7; range: 20.0-167.3 months). Mean CARS score at initial
      evaluation was 36.1 (SD: 6.3; range: 21.5-48). Mean DQ or IQ at initial
      evaluation was 0.65 (SD: 0.20; range: 0.16-1.10). There was no significant
      difference in socioeconomic status between DQ/IQ groups. CARS scores among
      children with an initial DQ or IQ <0.70 showed no significant decrement with
      time. In contrast, CARS scores among children with an initial DQ or IQ >or=0.70
      showed a significant decrement with time, which could be modeled by the formula
      CARS = 37.93 - [(0.12 x age in months at first visit) + (0.23 x period)]. The
      predicted CARS scores generated by this model correlated with the observed values
      (r = 0.71) and explained 50% of the variability in the CARS scores for this
      group. CONCLUSIONS: These data provide preliminary validation of a statistical
      model for clinical outcome of ASD on the basis of 3 parameters: age, degree of
      atypicality, and level of intelligence. This model, if replicated in a
      prospective, population-based sample that is controlled for treatment modalities,
      will enhance our ability to offer a prognosis for the child with ASD and will
      provide a benchmark against which to judge the putative benefits of various
      treatments for ASD. Our model may also be useful in etiologic and epidemiologic
      studies of ASD, because different causes of ASD are likely to follow different
      developmental trajectories along these 3 parameters.

PMID- 15995042
TI  - Spectrum of gross motor function in extremely low birth weight children with
      cerebral palsy at 18 months of age.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      cerebral palsy (CP) diagnoses as measured by the topographic distribution of the
      tone abnormality with level of function on the Gross Motor Function
      Classification System (GMFCS) and developmental performance on the Bayley Scales
      of Infant Development II (BSID-II). It was hypothesized that (1) the greater the
      number of limbs involved, the higher the GMFCS and the lower the BSID-II Motor
      Scores and (2) there would be a spectrum of function and skill achievement on the
      GMFCS and BSID-II Motor Scores for children in each of the CP categories.
      METHODS: A multicenter, longitudinal cohort study was conducted of 1860 extremely
      low birth weight (ELBW) infants who were born between August 1, 1995 and February
      1, 1998, and evaluated at 18 to 22 months' corrected age. Children were
      categorized into impairment groups on the basis of the typography of neurologic
      findings: spastic quadriplegia, triplegia, diplegia, hemiplegia, monoplegia,
      hypotonic and/or athetotic CP, other abnormal neurologic findings, and normal.
      The neurologic category then was compared with GMFCS level and BSID-II Motor
      Scores. RESULTS: A total of 282 (15.2%) of the 1860 children evaluated had CP.
      Children with more limbs involved had more abnormal GMFCS levels and lower BSID
      II scores, reflecting more severe functional limitations. However, for each CP
      diagnostic category, there was a spectrum of gross motor functional levels and
      BSID-II scores. Although more than 1 (26.6%) in 4 of the children with CP had
      moderate to severe gross motor functional impairment, 1 (27.6%) in 4 had motor
      functional skills that allowed for ambulation. CONCLUSIONS: Given the range of
      gross motor skill outcomes for specific types of CP, the GMFCS is a better
      indicator of gross motor functional impairment than the traditional
      categorization of CP that specifies the number of limbs with neurologic
      impairment. The neurodevelopmental assessment of young children is optimized by
      combining a standard neurologic examination with measures of gross and fine motor
      function (GMFCS and Bayley Psychomotor Developmental Index). Additional studies
      to examine longer term functional motor and adaptive-functional developmental
      skills are required to devise strategies that delineate therapies to optimize
      functional performance.

PMID- 15995043
TI  - The association between having a medical home and vaccination coverage among
      children eligible for the vaccines for children program.
AB  - BACKGROUND: The Vaccines for Children (VFC) program is designed to reduce the
      cost of vaccines for vulnerable children, including Medicaid-eligible children,
      American Indian/Alaska Native children, uninsured children, and underinsured
      children whose health insurance does not cover the cost of vaccinations. A
      desired consequence of the program is to promote comprehensive continuous medical
      care within a medical home for these children. OBJECTIVES: To explore how having
      a medical home is associated with vaccination coverage among children eligible
      for the program. PARTICIPANTS: A total of 24514 children 19 to 35 months of age
      sampled by the National Immunization Survey. DESIGN: VFC eligibility was
      evaluated for 24514 children 19 to 35 months of age who were sampled by the
      National Immunization Survey. Children were considered to have a medical home if
      they had a doctor, nurse, or physician's assistant who provided them with ongoing
      routine care, including well-child care, preventive care, and sick care,
      according to their parents. Sampled children were determined to be 4:3:1:3:3 up
      to-date (UTD) if their vaccination providers reported administering >or=4 doses
      of diphtheria-tetanus toxoids-acellular pertussis vaccine, >or=3 doses of polio
      vaccine, >or=1 dose of measles-mumps-rubella vaccine, >or=3 doses of Haemophilus
      influenzae type b vaccine, and >or=3 doses of hepatitis B vaccine. RESULTS:
      Nationally, 44.9% of all children were VFC eligible and 93.0% of the VFC-eligible
      children received all vaccine doses at a provider enrolled in the VFC program.
      Compared with children who were not VFC eligible, VFC-eligible children were less
      likely to be UTD (70.8% vs 77.7%) and less likely to have a medical home (82.1%
      vs 95.0%). However, among VFC-eligible children, children who had a medical home
      were significantly more likely to be UTD, compared with children who did not have
      a medical home (72.3% vs 63.5%). Also, among VFC-eligible children who had a
      medical home, children who used their medical home consistently to receive all of
      their vaccination doses were significantly more likely to be UTD, compared with
      children who did not receive all of their doses from their medical home (75.3% vs
      65.7%). Finally, the 4:3:1:3:3 vaccination coverage rate among VFC-eligible
      children who received all of their vaccination doses from their medical home was
      not significantly different from that among non-VFC-eligible children, after
      controlling for significant differences in sociodemographic factors between these
      groups (adjusted difference: 2.8%; 95% confidence interval: -0.1% to 5.7%).
      CONCLUSIONS: Although the vaccination coverage rate among VFC-eligible children
      who had a medical home and received all vaccine doses from their medical home was
      essentially equivalent to that of non-VFC-eligible children, substantial
      percentages of VFC-eligible children either did not have a medical home or did
      not use their medical home to receive all of their recommended vaccinations. The
      vaccination coverage rate among these children was significantly lower. This
      suggests that there may be opportunities to increase vaccination coverage by
      removing barriers that prevent the adoption and consistent use of a medical home
      among these children.

PMID- 15995044
TI  - Clinical and biological features at diagnosis in 40 children with chronic myeloid
      leukemia.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical and biological
      characteristics at diagnosis in children and adolescents with chronic myelogenous
      leukemia (CML) in contemporary practice. METHODS: Analysis was conducted on data
      from 3 prospective trials conducted in children and adolescents with CML. Forty
      pediatric patients were evaluated in 16 French pediatric oncology units between
      1991 and 2003. RESULTS: The disease predominately affected children who were
      older than 10 years (67% of the patients), with a higher prevalence in boys than
      girls (gender ratio: 1.5). Approximately 20% of cases were diagnosed
      incidentally. The main presenting symptoms were asthenia, weight loss, and
      complaints related to splenomegaly. Occasional patients presented with signs
      evocative of leukostasis. Symptoms were more common in patients with splenic
      enlargement, which was present in 70% of patients, and higher leukocyte counts.
      Markedly raised leukocyte counts were common (median white blood cell count: 242
      x 10(9)/L). The age and the gender of the patients had no effect on the leukocyte
      count, the hemoglobin level, or the platelet count. A predominance of b3a2
      transcript was observed in the 16 children who were studied for the type of
      chimeric BCR-ABL mRNA. CONCLUSIONS: This is largest reported series of CML at
      diagnosis in children and adolescents. It shows that the characteristics of CML
      seem to differ in children compared with previously published adult series; in
      particular, the presenting leukocyte counts are often higher in children.

PMID- 15995045
TI  - The Brookline Early Education Project: a 25-year follow-up study of a family
      centered early health and development intervention.
AB  - BACKGROUND: Clinicians, scientists, and policy makers are increasingly taking
      interest in the long-term outcomes of early intervention programs undertaken
      during the 1960s and 1970s, which were intended to improve young children's
      health and educational prospects. The Brookline Early Education Project (BEEP)
      was an innovative, community-based program that provided health and developmental
      services for children and their families from 3 months before birth until entry
      into kindergarten. It was open to all families in the town of Brookline and to
      families from neighboring Boston, to include a mixture of families from suburban
      and urban communities. The goal of the project, which was administered by the
      Brookline Public Schools, was to ensure that children would enter kindergarten
      healthy and ready to learn. OBJECTIVE: Outcome studies of BEEP and comparison
      children during kindergarten and second grade demonstrated the program's
      effectiveness during the early school years. The goal of this follow-up study was
      to test the hypotheses that BEEP participants, in comparison with their peers,
      would have higher levels of educational attainment, higher incomes, and more
      positive health behaviors, mental health, and health efficacy during the young
      adult period. METHODS: Participants were young adults who were enrolled in the
      BEEP project from 1973 to 1978. Comparison subjects were young adults in Boston
      and Brookline who did not participate in BEEP but were matched to the BEEP group
      with respect to age, ethnicity, mother's educational level, and neighborhood
      (during youth). A total of 169 children were enrolled originally in BEEP and
      monitored through second grade. The follow-up sample included a total of 120
      young adults who had participated in BEEP as children. The sample differed from
      the original BEEP sample in having a slightly larger proportion of college
      educated mothers and a slightly smaller proportion of urban families but
      otherwise resembled the original BEEP sample. The demographic features of the
      BEEP and comparison samples were similar. The young adults were asked to complete
      a survey that focused on the major domains of educational/functional outcomes and
      health/well-being. The study used a quasi-experimental causal-comparative design
      involving quantitative analyses of differences between the BEEP program and
      comparison groups, stratified according to community. Hypotheses were tested with
      analysis of variance and multivariate analysis of variance techniques. Analyses
      of the hypotheses included the main effects of group (BEEP versus comparison
      sample) and community (suburban versus urban location), as well as their
      interaction. RESULTS: Young adults from the suburban community had higher levels
      of educational attainment than did those in the urban group, with little
      difference between the suburban BEEP and comparison groups. In the urban group,
      participation in the BEEP program was associated with completing >1 additional
      year of schooling. Fewer BEEP young adults reported having a low income (less
      than 20000 dollars); the income differences were accounted for largely by the
      urban participants. The percentage of subjects with private health insurance was
      significantly lower in the urban group overall, but the BEEP urban group had
      higher rates of private insurance than did the comparison group. More than 80% of
      both suburban samples reported being in very good or excellent health; the 2
      urban groups had significantly lower ratings, with 64% of the BEEP group and only
      41.67% of the comparison group reaching this standard. Overall, suburban
      participants reported more positive health behaviors, more perceived competence,
      and less depression. Among the urban samples, however, participation in BEEP was
      associated with higher levels of health efficacy, more positive health behaviors,
      and less depression than their peers. CONCLUSIONS: No previous study has focused
      as extensively on health-related outcomes of early education programs. BEEP
      participants living in urban communities had advantages over their peers in
      educational attainment, income, health, and well-being. The educational
      advantages found for BEEP participants in the early years of schooling included
      executive skills such as planning, organizing, and completing school-related
      tasks. It is likely that these early advantages in executive function extended
      beyond education-related tasks to other activities as participants became
      responsible for their own lives. The long-term benefits revealed in this study
      are consistent with the findings of previous long-term studies that indicated
      that participants in high-quality intervention programs are less likely to cost
      taxpayers money for health, educational, and public assistance services. The BEEP
      program appears to have somewhat blunted differences between the urban and
      suburban groups. The results of this study add to the growing body of findings
      that indicate that long-term benefits occur as the result of well-designed,
      intensive, comprehensive early education. The health benefits add a unique and
      important extension to the findings of other studies.

PMID- 15995046
TI  - Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8
      years of age, with 1 vs 2 doses.
AB  - OBJECTIVE: To evaluate the effectiveness of 1 and 2 doses of the 2003-2004
      influenza vaccine in preventing medically attended influenza-like illness (ILI)
      among children 6 to 23 months and 6 months to 8 years of age. DESIGN AND METHODS:
      Outpatient and emergency department visits and immunization records were used to
      conduct a retrospective cohort study among children 6 months to 8 years of age.
      ILI and pneumonia and influenza (P&I) outcomes were defined on the basis of
      International Classification of Diseases, Ninth Revision, codes. Influenza
      vaccine effectiveness (VE) was calculated as (1 - hazard rate ratio) x 100.
      RESULTS: A total of 29726 children were included in the analyses; 17.3% were 6 to
      23 months of age. By November 19, 2003, the start of peak influenza activity,
      7.5% and 9.9% of children 6 months to 8 years were fully or partially vaccinated
      against influenza, respectively. For fully vaccinated children 6 to 23 months of
      age, VE against ILI and P&I was 25% and 49%, respectively. No statistically
      significant reduction in ILI or P&I rates was observed for partially vaccinated
      children 6 to 23 months of age (-3% and 22%, respectively). For fully vaccinated
      children 6 months to 8 years of age, VE against ILI and P&I was 23% and 51%,
      respectively. For partial vaccination, VE was significant only for P&I (23%).
      CONCLUSIONS: Despite a suboptimal match between the influenza vaccine and
      predominant circulating strains, influenza vaccination provided substantial
      protection for fully vaccinated children and possibly some protection for
      partially vaccinated children <9 years of age. These findings support vaccinating
      targeted children even when the vaccine match is suboptimal, and they highlight
      the need to vaccinate previously unvaccinated children with 2 doses for optimal
      protection.

PMID- 15995047
TI  - Safety and immunogenicity of the American Academy of Pediatrics--recommended
      sequential pneumococcal conjugate and polysaccharide vaccine schedule in
      pediatric solid organ transplant recipients.
AB  - OBJECTIVE: Solid organ transplant recipients are at increased risk for invasive
      pneumococcal disease. The American Academy of Pediatrics recommends immunization
      with sequential pneumococcal vaccines for this group; however, data are lacking.
      Accordingly, this study was designed to evaluate the safety and immunogenicity of
      the recommended regimen. METHODS: Pediatric solid organ transplant recipients (n
      = 25) between 2 and 18 years of age who had not previously received 7-valent
      conjugate pneumococcal vaccine (PCV7) were enrolled. These patients received 2
      doses of the PCV7 and a single dose of the 23-valent polysaccharide pneumococcal
      vaccine (23V). Each vaccine dose was given 2 months apart. Healthy age-matched
      controls (n = 23) were enrolled for comparison. Controls received a single dose
      of PCV7 followed 2 months later by a single dose of 23V. Antibody concentrations
      to serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were measured by enzyme
      linked immunosorbent assay prevaccination, 2 months after each vaccine dose and 5
      to 7 months after 23V. Local and systemic reactions to each vaccine dose were
      recorded. RESULTS: Systemic and injection-site reactions were comparable between
      the 2 groups. Significant rises in serotype-specific pneumococcal antibody
      geometric mean concentrations from prevaccination levels were observed in both
      groups; however, final antibody responses to serotypes 1, 4, 9V, 14, 18C, 19F,
      and 23F were significantly lower in solid organ transplant recipients compared
      with the control group. Antibody concentrations did not increase significantly
      among solid organ transplant patients after the second dose of PCV7. No
      additional increase in PCV7-associated serotype-specific antibody levels was
      observed after the 23V dose in both groups. Heart transplant recipients had lower
      antibody responses compared with liver transplant recipients. CONCLUSIONS:
      Although the pneumococcal vaccine regimen was safe and immunogenic among
      pediatric solid organ transplant recipients, the patients did not seem to benefit
      from the second dose of PCV7 or from the 23V dose given 2 months later.
      Additional studies are needed to determine the number of PCV7 doses and the
      interval between PCV7 and 23V to induce optimal responses.

PMID- 15995048
TI  - Clinical effectiveness and cost-effectiveness of the use of the
      thyroxine/thyroxine-binding globulin ratio to detect congenital hypothyroidism of
      thyroidal and central origin in a neonatal screening program.
AB  - CONTEXT: Since the introduction of screening for congenital hypothyroidism (CH)
      in 1974, the optimal laboratory strategy has been the subject of debate.
      OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of various
      types of thyroxine (T(4))-based strategies to screen for CH. DESIGN, SETTING, AND
      PARTICIPANTS: In the Netherlands, since January 1, 1995, a primary T(4)
      determination with supplemental thyroid-stimulating hormone (TSH) and T(4)
      binding globulin (TBG) measurements has been used. Results were calculated from
      cumulative findings for 1181079 children screened between January 1, 1995, and
      December 31, 2000. MAIN OUTCOME MEASURES: Rates of detection of patients with CH
      of thyroidal origin (CH-T) or CH of central origin (CH-C), false-positive rates,
      laboratory costs, and costs of initial diagnostic evaluations. RESULTS: All known
      infants (n = 393) with CH-T and 92% (n = 66) of infants with CH-C were detected
      on the basis of low T(4) levels, TSH elevation, and/or low T(4)/TBG ratios. If
      the decision to refer had been based solely on TSH elevation, then 94% of
      patients with CH-T and none of the patients with CH-C would have been detected.
      If low T(4) levels (<or=-3.0 SD) and TSH elevation had been used as the criteria
      for referral, then the rates of detection would have been 96% for CH-T and 31%
      for CH-C. The false-positive rates for the 3 approaches were 0.5, 3.3, and 4.7
      cases per case detected, respectively. The introduction of the T(4)/TBG ratio
      into a program using a primary T(4) with supplemental TSH approach generates an
      extra cost of 11206 dollars per additional case detected. The average costs to
      detect 1 patient are comparable for the 3 approaches. In addition, our data
      revealed a substantially greater prevalence of CH-C than reported previously (1
      case per 16404 children, compared with earlier estimates of 1 case per 26000
      infants to 1 case per 29000 infants). CONCLUSIONS: The T(4) plus TSH plus TBG
      approach is a recommendable strategy for neonatal CH screening. It offers
      outstanding detection of patients with CH-C, in addition to those with CH-T, with
      acceptable costs.

PMID- 15995049
TI  - Pediatricians' reported practices regarding developmental screening: do
      guidelines work? Do they help?
AB  - BACKGROUND: In 2001, the American Academy of Pediatrics (AAP) adopted a policy
      that all infants and young children should be screened for developmental delays
      at regular intervals. The policy statement promoted the use of valid reliable
      instruments. It is unknown, however, what proportion of pediatricians follow this
      recommendation and whether such a practice is associated with improved
      identification of children with developmental difficulties. OBJECTIVES: To
      describe the use of developmental screening tests among board-certified
      pediatricians practicing general pediatrics and to determine the association
      between standardized screening and the self-reported identification of children
      with developmental difficulties. METHODS: We mailed a survey to a random sample
      of AAP members. We used multivariate logistic/linearregression analyses to
      determine the association between standardized screening and the self-reported
      identification of children with developmental disabilities. RESULTS: Of the 1617
      surveys mailed, 894 were returned, for a response rate of 55%. Of the
      respondents, 646 practiced general pediatrics and were included in the analysis.
      Seventy-one percent of those pediatricians indicated that they almost always used
      clinical assessment without an accompanying screening instrument to identify
      children with developmental delays. Only 23% indicated that they used a
      standardized screening instrument. The most commonly used instrument was the
      Denver II. Logistic regression modeling demonstrated odds ratios between 1.71 and
      1.90 for a >10% rate of identification of developmental problems among patients
      of pediatricians reporting standardized screening. Each adjusted odds ratio
      bordered on statistical significance. Linear-regression models estimating the
      difference in mean proportions of children identified with developmental problems
      across screening groups failed to show a statistically or clinically significant
      difference in physician-reported identification rates. CONCLUSIONS: Our findings
      indicate that, despite the AAP policy and national efforts to improve
      developmental screening in the primary care setting, few pediatricians use
      effective means to screen their patients for developmental problems. It is
      uncertain whether standardized screening, as it is practiced currently, is
      associated with an increase in the self-reported identification of children with
      developmental disabilities.

PMID- 15995050
TI  - Initial neurologic presentation in young children sustaining inflicted and
      unintentional fatal head injuries.
AB  - BACKGROUND: It remains unclear if fatal brain injuries in young children are
      characterized by immediate rapid deterioration or can present after an initial
      period of lucidity. This issue has legal implications in child abuse, for which
      understanding the clinical course affects perpetrator identification. OBJECTIVE:
      To determine patterns of neurologic presentation on hospital admission in infants
      and toddlers who die of inflicted and unintentional injury. DESIGN/METHODS: Data
      on children <48 months of age who sustained a fatal head injury from 1986-2002
      were extracted from the Pennsylvania Trauma Outcomes Study. Only those with
      external-causes-of-injury codes for inflicted injury, falls, and motor vehicle
      crashes (MVCs) with a recorded Glasgow Coma Scale (GCS) on admission were
      included. The GCS was compared across mechanisms and age groups (0-11, 12-23, 24
      35, and 36-47 months). RESULTS: Of the 314 fatally injured children, 37%
      sustained inflicted injury, 13% sustained a fall, and 49% sustained an MVC. At
      admission, 6.8% of all children had a GCS score of >7, and 1.9% presented with a
      GCS score of >12 (lucid). The incidence of admission a GCS score of >7 varied by
      mechanism. Overall, children with inflicted injury were 3 times more likely to
      present with a GCS score of >7 than those injured in MVCs (odds ratio [OR]: 3.6;
      95% confidence interval [CI]: 1.2-10.3), but incidence of a GCS score of >7 did
      not differ between inflicted injuries and falls. Similarly, when considering only
      those children >or=24 months old, a GCS score of >7 did not differ by mechanism.
      In contrast, in those <24 months old, children who died as a result of inflicted
      injury were >10 times more likely to have a GCS score of >7 than those who died
      as a result of a MVC (OR: 9.36; 95% CI: 1.3-80.9). CONCLUSIONS: The data suggest
      an age- and mechanism-dependent presentation of neurologic status in children
      with fatal head injury. Although infrequent, young victims of fatal head trauma
      may present as lucid (GCS score: >12) before death. Furthermore, children <48
      months old sustaining inflicted injury are 3 times more likely to be assessed
      with a moderate GCS score (>7) than those in MVCs. This effect is amplified in
      the youngest children (<24 months old): those with inflicted injury were 10 times
      more likely to present with moderate GCS scores than those in MVCs. In addition,
      this youngest age group seems to be overrepresented in those who present as lucid
      (GCS score: >12 [5 of 6]). It is unclear whether these differences are the result
      of inadequate tests to evaluate consciousness in younger children or differences
      in biomechanical mechanisms of inflicted trauma.

PMID- 15995051
TI  - Adenoidectomy does not significantly reduce the incidence of otitis media in
      conjunction with the insertion of tympanostomy tubes in children who are younger
      than 4 years: a randomized trial.
AB  - OBJECTIVE: To evaluate the efficacy of adenoidectomy in reducing the incidence of
      otitis media among children who are younger than 4 years and receive tympanostomy
      tubes. METHODS: A randomized trial was conducted at a tertiary center clinic. A
      total of 217 children who were aged 12 to 48 months and had recurrent acute
      otitis media (>3 episodes during the past 6 months) or chronic otitis media with
      effusion, no obstructive symptoms as a result of adenoid enlargement, and no
      previous surgical intervention were enrolled in the study. Adenoidectomy in
      conjunction with the insertion of tympanostomy tubes or insertion of tympanostomy
      tubes without adenoidectomy was studied. The number of otitis media episodes
      during the follow-up period of 12 months was measured. RESULTS: During the follow
      up, the mean number of otitis media episodes was 1.7 among children who underwent
      adenoidectomy with concurrent insertion of tympanostomy tubes and 1.4 among
      children who received tympanostomy tubes only. The risk for recurrent otitis
      media (>or=3 episodes) could not be reduced by adenoidectomy (odds ratio: 1.66;
      95% confidence interval: 0.80-3.46). CONCLUSION: Adenoidectomy does not
      significantly reduce the incidence of acute otitis media in otitis prone children
      who are younger than 4 years and receive tympanostomy tubes.

PMID- 15995052
TI  - Hormonal effects in infants conceived by assisted reproductive technology.
AB  - OBJECTIVE: The purpose of this report is to describe 7 infants conceived by
      assisted reproductive technology (ART) who presented with breast development
      and/or pubic hair. The clinical presentation in these infants raises awareness
      that an altered intrauterine hormonal milieu may impact the fetal and infant
      stages of children conceived by ART. METHODS: Between May 2001 and April 2004, 7
      children between the ages of 5 and 21 months conceived by ART were referred by
      their pediatricians to the Division of Pediatric Endocrinology at the New York
      University School of Medicine for evaluation of possible precocious puberty.
      Patients were evaluated for the possibility of centrally mediated precocious
      puberty and pseudoprecocious puberty, with a possible ovarian or adrenal origin.
      RESULTS: Endocrine evaluation in all patients indicated sex-steroid and hormone
      levels in the prepubertal range; pelvic sonography confirmed prepubertal ovaries
      with unstimulated uteri. Clinical follow-up of our patients thus far has not
      revealed progression of breast development, pubarche, or elevation in sex
      steroids. CONCLUSIONS: It is well established that the developing endocrine
      system in the fetus and maturation of endocrine-control systems are influenced by
      hormone concentrations in the fetus. Whether ART alters the intrauterine hormonal
      milieu for the growing fetus conceived by ART is as yet unknown and is an area of
      ongoing investigation. Patients conceived through ART, including our patients who
      presented with hormonal manifestations, will need to be monitored throughout
      childhood and into adolescence and adulthood to determine if any perturbation
      exists on the timing of puberty and later fertility.

PMID- 15995053
TI  - The Food and Drug Administration's deliberations on antidepressant use in
      pediatric patients.
AB  - On February 2, 2004, the Food and Drug Administration organized a joint meeting
      of the Neuro-Psychopharmacologic Advisory Committee and Pediatric Subcommittee of
      the Anti-Infective Drugs Advisory Committee to examine the occurrence of
      suicidality in clinical trials that investigate the use of the newer
      antidepressant drugs in pediatric patients. Committee members reconvened on
      September 13-14, 2004, and concluded that there was a causal link between the
      newer antidepressants and pediatric suicidality. This article provides a summary
      of the Food and Drug Administration deliberations for the pediatric clinician. We
      also provide research, regulation, education, and practice implications for care
      for children and adolescents who may be eligible for treatment with these
      medications.

PMID- 15995054
TI  - Screening and interventions for overweight in children and adolescents:
      recommendation statement.
AB  - The U.S. Preventive Services Task Force (USPSTF) is an independent panel of non
      federal experts in prevention and primary care that systematically reviews the
      evidence of effectiveness and develops recommendations for clinical preventive
      services. This recommendation addresses the evidence for the accuracy of
      screening children and adolescents using BMI, the effectiveness of behavioral and
      pharmacologic interventions in improving health outcomes in these children, and
      the potential harms of routine screening and intervention. Using USPSTF
      methodology, an analytic framework with key questions was developed to guide the
      systematic review, which serves as the basis for this recommendation. The number
      of children and adolescents who are overweight has more than doubled in the last
      25 years. Childhood and adolescent overweight is associated with increased health
      risks. The USPSTF found insufficient evidence for the effectiveness of behavioral
      counseling or other preventive interventions with overweight children and
      adolescents that can be conducted in primary care settings. Currently, available
      studies are limited by factors such as small sample sizes, poor generalizability,
      and variable follow-up. Based upon this critical gap in the evidence for
      effectiveness, the USPSTF concludes that the evidence is insufficient to
      recommend for or against routine screening for overweight in children and
      adolescents as a means to prevent adverse health outcomes ("I" recommendation).
      There are several gaps in the research evidence on screening and interventions
      for overweight children and adolescents in the primary care setting. Research is
      needed to provide well-defined and effective approaches to medical and
      psychological screening in children, as well as effective clinical approaches for
      the prevention and treatment of overweight in children that can be implemented by
      primary care clinicians.

PMID- 15995055
TI  - Encephalopathy of prematurity includes neuronal abnormalities.

PMID- 15995056
TI  - Intravenous immunoglobulin in the treatment of childhood Guillain-Barre syndrome:
      a randomized trial.

PMID- 15995057
TI  - Understanding abnormalities in vascular specification and remodeling.

PMID- 15995058
TI  - The steroid odyssey in croup.

PMID- 15995059
TI  - Thinking outside the (black) box: antidepressants, suicidality, and research
      synthesis.

PMID- 15995060
TI  - Pediatricians and antidepressant medications: black box or black hole?

PMID- 15995061
TI  - Screening for overweight in children and adolescents: where is the evidence? a
      commentary by the childhood obesity working group of the US Preventive Services
      Task Force.

PMID- 15995062
TI  - Screening for overweight in children and adolescents: a call to action.

PMID- 15995063
TI  - Spanning the boundary between clinics and communities to address overweight and
      obesity in children.

PMID- 15995064
TI  - Living a normal life with the nondominant hemisphere: magnetic resonance imaging
      findings and clinical outcome for a patient with left-hemispheric
      hydranencephaly.
AB  - In hemihydranencephaly, the human brain lacks 1 complete hemisphere. An occlusion
      of the carotid artery, affecting all supplied territories, is thought to be the
      underlying mechanism. This extremely rare disorder, of which only 7 cases have
      been reported to date, is thought to occur before the last trimester of gestation
      (20th to 27th week), after neural migration but before synaptogenesis. We report
      on a 36-year-old man born at term, with no complications, from nonconsanguineous
      healthy parents. Cranial computed tomography had been performed because of left
      sided headaches. Because of the imaging findings, the patient presented at our
      institution for additional MRI and clinical testing (including the Motor Activity
      Log, Wolf motor function test, 2-point discrimination test, Purdue pegboard test,
      gross motor function test, Physician Rating Scale, and Aachener aphasia test,
      including patterns for spontaneous speech, repetition, naming, comprehension,
      written language, and the token test). The patient's disabilities were related to
      deficits in fine motor control and reduced precision. Therefore, the patient was
      unable to perform the Purdue pegboard test with his affected hand. According to
      the Aachener aphasia test, no aphasia could be demonstrated for this strongly
      left-handed patient. Strong mirror movements were found. Cortical reorganization
      is possible if damage occurs in very early childhood. Motor function and speech
      were controlled by the remaining, nonaffected hemisphere, with a remarkable
      outcome. Because the damage is thought to occur before synaptogenesis, existing
      or prepared cortical areas and pathways have the potential to execute the lacking
      functions of the destroyed hemisphere.

PMID- 15995065
TI  - Not your routine foreign body: endobronchial tuberculosis in an infant.
AB  - Foreign-body aspiration is a common cause of respiratory distress among children.
      Here we describe an 8-month-old, previously 34-week premature, male patient who
      presented with a 1-day history of fever and increased work of breathing. Of note,
      3 weeks before presentation, the patient had been treated with orally
      administered amoxicillin for presumed pneumonia and exhibited good clinical
      response. No chest radiograph was obtained at that time. A current chest
      radiograph revealed hyperexpansion of the left lung, with a mediastinal shift.
      Although the patient was referred because of possible foreign-body aspiration, no
      clear history of an aspiration event was obtained, and computed tomographic scans
      of the chest were recommended. These showed extensive hilar and mediastinal
      lymphadenopathy, resulting in obstruction of the left bronchus. Bronchoscopy
      revealed a cheesy granulomatous mass in the left mainstem bronchus, which was
      ball-valving into the upper bronchus. Removal resulted in improvement of the
      patient's respiratory status. Pathology, bronchial lavage, and gastric aspirate
      specimens all revealed acid-fast bacilli, consistent with Mycobacterium
      tuberculosis infection. This unusual presentation of tuberculosis may become more
      common in the United States as the incidence of immigrants carrying tuberculosis
      increases.

PMID- 15995066
TI  - Acute arsenic poisoning in two siblings.
AB  - We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old
      male infant and his 2-year-old sister. Each child ingested solubilized inorganic
      arsenic from an outdated pesticide that was misidentified as spring water. The 4
      month-old child ingested a dose of arsenic that was lethal despite extraordinary
      attempts at arsenic removal, including chelation therapy, extracorporeal membrane
      oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well
      with conventional therapy.

PMID- 15995067
TI  - Pediatric care recommendations for freestanding urgent care facilities.
AB  - Freestanding urgent care centers are not emergency departments or medical homes,
      yet they are sometimes used as a source of pediatric care. The purpose of this
      policy statement is to provide updated and expanded recommendations for ensuring
      appropriate stabilization in pediatric emergency situations and timely and
      appropriate transfer to a hospital for definitive care when necessary.

PMID- 15995068
TI  - Model contractual language for medical necessity for children.
AB  - The term "medical necessity" is used by Medicare and Medicaid and in insurance
      contracts to refer to medical services that are generally recognized as
      appropriate for the diagnosis, prevention, or treatment of disease and injury.
      There is no consensus on how to define and apply the term and the accompanying
      rules and regulations, and as a result there has been substantial variation in
      medical-necessity definitions and interpretations. With this policy statement,
      the American Academy of Pediatrics hopes to encourage insurers to adopt more
      consistent medical-necessity definitions that take into account the needs of
      children.

PMID- 15995069
TI  - Pediatrician workforce statement.
AB  - This statement discusses the importance of pediatrician-workforce issues and
      their relevance to the provision of pediatric health care. It reviews previous
      work in the health policy arena on physician and pediatrician workforce. Key
      pediatrician-workforce trends are described, including the growth in the number
      of pediatricians in relation to the child population, the increase in the number
      of female pediatricians, the role of international medical graduates, the
      diversity of the pediatrician workforce, the contributions of internal medicine
      pediatrics physicians, the increasing number of nonpediatrician providers of
      pediatric care, geographic distribution of physicians, and the future of
      pediatric subspecialists. Methods of influencing the pediatrician workforce are
      also considered. In the concluding series of recommendations, the statement
      identifies both overarching policy goals for the pediatrician workforce and
      implementation strategies designed to ensure that all of America's infants,
      children, adolescents, and young adults have access to appropriate pediatric
      health care.

PMID- 15995070
TI  - Screening for retinopathy in the pediatric patient with type 1 diabetes mellitus.
AB  - Diabetic retinopathy (DR) is the leading cause of blindness in young adults in
      the United States. Early identification and treatment of DR can decrease the risk
      of vision loss in affected patients. This clinical report reviews the risk
      factors for the development of DR and screening guidance for pediatric patients
      with type 1 diabetes mellitus.

PMID- 15995071
TI  - Adolescent pregnancy: current trends and issues.
AB  - The prevention of unintended adolescent pregnancy is an important goal of the
      American Academy of Pediatrics and our society. Although adolescent pregnancy and
      birth rates have been steadily decreasing, many adolescents still become
      pregnant. Since the last statement on adolescent pregnancy was issued by the
      Academy in 1998, efforts to prevent adolescent pregnancy have increased, and new
      observations, technologies, and prevention effectiveness data have emerged. The
      purpose of this clinical report is to review current trends and issues related to
      adolescent pregnancy, update practitioners on this topic, and review legal and
      policy implications of concern to pediatricians.

PMID- 15995072
TI  - AAP publication reaffirmed, May 2004.

PMID- 15995074
TI  - First rule: choose your battles wisely.

PMID- 15995075
TI  - Response to "Scientifically unsupported and supported interventions for childhood
      psychopathology: a summary".

PMID- 15995077
TI  - Response to "Scientifically unsupported and supported interventions for childhood
      psychopathology: a summary".

PMID- 15995079
TI  - Childhood obesity: benefits of lifestyle-modification therapy.

PMID- 15995080
TI  - Erythromelalgia: small-fiber neuropathy by any other name?

PMID- 15995082
TI  - Probiotics and necrotizing enterocolitis.

PMID- 15995085
TI  - Emergency department wait times.

PMID- 15995086
TI  - Continuity of care from the resident's perspective.

PMID- 15995087
TI  - Exhaled nitric oxide levels during acute asthma exacerbation.
AB  - OBJECTIVES: Fractional exhaled nitric oxide (FE(NO)) has been shown in laboratory
      settings and trials of patients with stable asthma to correlate with the degree
      of airway inflammation. The authors hypothesized that the technique of measuring
      FE(NO) would be reproducible in the setting of acute asthma in the emergency
      department (ED) and that the FE(NO) results during ED visits would potentially
      predict disposition, predict relapse following discharge, and correlate with the
      National Institutes of Health (NIH) asthma severity scale and peak expiratory
      flow measurements. METHODS: The authors prospectively measured FE(NO) in a
      convenience sample of ED patients with acute exacerbations of asthma, both at the
      earliest possible opportunity and then one hour later. Each assessment point
      included triplicate measurements to assess reproducibility. The authors also
      performed spirometry and classified asthma severity using the NIH asthma severity
      scale. Discharged patients were contacted in 72 hours to determine whether their
      asthma had relapsed. RESULTS: The authors discontinued the trial (n = 53) after a
      planned interim analysis demonstrated reproducibility (coefficient of variation,
      15%) substantially worse than our a priori threshold for precision (4%). There
      was no association between FE(NO) response and corresponding changes in
      spirometry or clinical scores. Areas under the receiver operating characteristic
      curves for the prediction of hospitalization and relapse were poor (0.579 and
      0.713, respectively). CONCLUSIONS: FE(NO) measurements in ED patients with acute
      asthma exacerbations were poorly reproducible and did not correlate with standard
      measures of asthma severity. These results suggest that using existing
      technology, FE(NO) is not a useful marker for assessing severity, response to
      treatment, or disposition of acute asthmatic patients in the ED.

PMID- 15995088
TI  - Comparison of the unstructured clinician estimate of pretest probability for
      pulmonary embolism to the Canadian score and the Charlotte rule: a prospective
      observational study.
AB  - OBJECTIVES: Clinical decision rules have been validated for estimation of pretest
      probability in patients with suspected pulmonary embolism (PE). However, many
      clinicians prefer to use clinical gestalt for this purpose. The authors compared
      the unstructured clinical estimate of pretest probability for PE with two
      clinical decision rules. METHODS: This prospective, observational study was
      conducted from October 2001 to July 2004 at an urban academic emergency
      department with an annual census of 105,000. A total of 2,603 patients were
      enrolled; mean age (+/- SD) was 45 (+/- 16) years, and 70% were female. All
      patients were evaluated for PE using a previously published protocol, including D
      dimer and alveolar dead space measurements, and selected use of pulmonary
      vascular imaging. All had 45-day follow-up. Interobserver agreement for each
      pretest probability estimation method was measured in a separate group of 154
      patients. RESULTS: The overall prevalence of PE was 5.8% (95% confidence interval
      [CI] = 4.9% to 6.8%). Most were deemed low risk for PE, including 69% by the
      unstructured estimate < 15%, 73% by the Canadian score < 2, and 88% by the
      Charlotte rule "safe." The corresponding prevalence of disease in each of these
      low-risk groups was 2.6%, 3.0%, and 4.2%. Weighted Cohen's kappa values were 0.60
      (95% CI = 0.46 to 0.74) for the unstructured clinical estimate < 15%, 0.47 (95%
      CI = 0.33 to 0.61) for the Canadian score < 2, and 0.85 (95% CI = 0.69 to 1.0)
      for the Charlotte rule "safe." CONCLUSIONS: The unstructured clinical estimate of
      low pretest probability for PE compares favorably with the Canadian score and the
      Charlotte rule. Interobserver agreement for the unstructured estimate is
      moderate.

PMID- 15995089
TI  - Paramedic response time: does it affect patient survival?
AB  - OBJECTIVES: One marker of quality emergency medical services care is measured by
      meeting an 8-minute response time guideline. This guideline was based on results
      of paramedic response times for nontraumatic cardiac arrest patients and has not
      been studied in unselected patients. The objective of this study was to evaluate
      the effect of paramedic response time on survival to hospital discharge in
      unselected patients in a large urban setting while controlling for a number of
      potentially important confounders, including level of illness severity. METHODS:
      This was a retrospective cohort study performed in an urban 911-based ambulance
      service system. Patients transported by paramedics to a single urban county
      teaching hospital from January 1, 1998, to December 31, 1998, were included. Data
      collected included patient demographics; paramedic response, scene, and transport
      times; the nature of the medical complaint; and whether the patient survived to
      hospital discharge. Multivariable logistic regression models were developed using
      response time as the primary independent variable and survival to hospital
      discharge as the dependent variable. Covariates included scene time, transport
      time, age, gender, and level of illness severity. RESULTS: Of 34,111 calls
      involving emergency response, 11,078 patients (32%) were transported to the study
      institution and 10,382 (94%) had response time data available. Of these, 9,559
      patients (92%) had data available to categorize them into groups based on their
      level of illness severity and were thus included in the study. A survival benefit
      was identified for response times <or=4 minutes (odds ratio [OR], 0.70; 95%
      confidence interval [CI] = 0.52 to 0.95). No survival benefit was identified when
      response time was modeled as a continuous variable (OR, 1.01; 95% CI = 0.98 to
      1.04) or when dichotomized at 8 minutes (OR, 1.06; 95% CI = 0.80 to 1.42).
      CONCLUSIONS: A paramedic response time within 8 minutes was not associated with
      improved survival to hospital discharge after controlling for several important
      confounders, including level of illness severity. However, a survival benefit was
      identified when the response time was within 4 minutes for patients with
      intermediate or high risk of mortality. Adherence to the 8-minute response time
      guideline in most patients who access out-of-hospital emergency services is not
      supported by these results.

PMID- 15995090
TI  - ABSCESS: applied bedside sonography for convenient evaluation of superficial soft
      tissue infections.
AB  - OBJECTIVES: Soft tissue infections are a common presenting complaint in the
      emergency department (ED). The authors sought to determine the utility of ED
      bedside ultrasonography (US) in detecting subcutaneous abscesses. METHODS:
      Between August 2003 and November 2004, a prospective, convenience sample of adult
      patients with a chief complaint suggestive of cellulitis and/or abscess was
      enrolled. US was performed by attending physicians or residents who had attended
      a 30-minute training session in soft tissue US. The treating physician recorded a
      yes/no assessment of whether he or she believed an abscess was present before and
      after the US examination. Incision and drainage (I + D) was the criterion
      standard when performed, while resolution on seven-day follow-up was the
      criterion standard when I + D was not performed. RESULTS: Sixty-four of 107
      patients had I + D-proven abscess, 17 of 107 had negative I + D, and 26 of 107
      improved with antibiotic therapy alone. The sensitivity of clinical examination
      for abscesses was 86% (95% confidence interval [CI] = 76% to 93%), and the
      specificity was 70% (95% CI = 55% to 82%). The positive predictive value was 81%
      (95% CI = 70% to 90%), and the negative predictive value was 77% (95% CI = 62% to
      88%). The sensitivity of US for abscess was 98% (95% CI = 93% to 100%), and the
      specificity was 88% (95% CI = 76% to 96%). The positive predictive value was 93%
      (95% CI = 84% to 97%), and the negative predictive value was 97% (95% CI = 88% to
      100%). Of 18 cases in which US disagreed with the clinical examination, US was
      correct in 17 (94% of cases with disagreement, chi(2) = 14.2, p = 0.0002).
      CONCLUSIONS: ED bedside US improves accuracy in detection of superficial
      abscesses.

PMID- 15995091
TI  - Transcutaneous electrical nerve stimulation reduces acute low back pain during
      emergency transport.
AB  - BACKGROUND: Patients with acute low back pain may require emergency transport
      because of pain and immobilization. Transcutaneous electrical nerve stimulation
      (TENS) is a nonpharmaceutical therapy for patients with low back pain. OBJECTIVE:
      To evaluate the efficacy of paramedic-administered TENS in patients with acute
      low back pain during emergency transport. METHODS: This was a prospective,
      randomized study involving 74 patients transported to hospital. The patients were
      randomly assigned to two groups: group 1 (n = 36) was treated with true TENS,
      while group 2 (n = 36) was treated with sham TENS. The authors recorded pain and
      anxiety as the main outcome variables using a visual analog scale (VAS). RESULTS:
      The authors recorded a significant (p < 0.01) pain reduction (mean +/- standard
      deviation) during transport in group 1 (79.2 +/- 6.5 mm VAS to 48.9 +/- 8.2 mm
      VAS), whereas pain scores remained unchanged in group 2 (75.9 +/- 16.4 mm VAS and
      77.1 +/- 11.2 mm VAS). Similarly, the scores for anxiety were significantly
      reduced (p < 0.01) in group 1 (81.7 +/- 7.9 mm VAS to 69.2 +/- 12.1 mm VAS) after
      treatment. No significant change was noted (84.5 +/- 5.8 mm VAS and 83.5 +/- 8.9
      mm VAS, respectively) in group 2. CONCLUSIONS: TENS was found to be effective and
      rapid in reducing pain during emergency transport of patients with acute low back
      pain and should be considered due to its ease of use and lack of side effects in
      the study population.

PMID- 15995092
TI  - An evaluation of two screening tools for cognitive impairment in older emergency
      department patients.
AB  - OBJECTIVES: Screening for cognitive impairment in older emergency department (ED)
      patients is recommended to ensure quality care. The Mini-Mental State Examination
      (MMSE) may be too long for routine ED use. Briefer alternatives include the Six
      Item Screener (SIS) and the Mini-Cog. The objective of this study was to describe
      the test characteristics of the SIS and the Mini-Cog compared with the MMSE when
      administered to older ED patients. METHODS: This institutional review board
      approved, prospective, randomized study was performed in a university-affiliated
      teaching hospital ED. Eligible patients were 65 years and older and able to
      communicate in English. Patients who were unable or unwilling to perform testing,
      who were medically unstable, or who received medications affecting their mental
      status were excluded. Patients were randomized to receive the SIS or the Mini-Cog
      by the treating emergency physician. Investigators administered the MMSE 30
      minutes later. An SIS score of <or=4, the Mini-Cog's scoring algorithm, and an
      MMSE score of <or=23 defined cognitive impairment. RESULTS: A total of 149 of 188
      approached patients were enrolled; 74 received the SIS and 75 the Mini-Cog. Fifty
      five percent were female, the average age was 75 years, and 23% had an MMSE score
      of <or=23. The SIS had a sensitivity of 94% (95% confidence interval [CI] = 73%
      to 100%) and a specificity of 86% (95% CI = 74% to 94%). The Mini-Cog had a
      sensitivity of 75% (95% CI = 48% to 93%) and a specificity of 85% (95% CI = 73%
      to 93%). CONCLUSIONS: The SIS, using a cutoff of <or=4 as impaired, is a
      promising test for ED use. It is short, easy to administer, and unobtrusive,
      allowing it to be easily incorporated into the initial assessment of older ED
      patients.

PMID- 15995093
TI  - The effect of financial incentives on adherence with outpatient human
      immunodeficiency virus testing referrals from the emergency department.
AB  - OBJECTIVES: Undiagnosed human immunodeficiency virus (HIV) infection is not
      uncommon among patients who seek care in urban inner-city emergency departments
      (EDs). The optimal method for providing appropriate HIV counseling, testing, and
      referral in this setting is unclear. A previous evaluation of an outpatient
      referral system for HIV testing among patients seen in the ED demonstrated that
      only 11% returned to be tested; of those tested, 7% were seropositive. The
      purpose of this study was to evaluate the effect of a financial incentive on the
      proportion of referred ED patients who completed outpatient HIV counseling and
      testing. METHODS: This was a quasi-experiment performed at an urban county
      teaching hospital. ED patients identified using Centers for Disease Control and
      Prevention guidelines as being at risk for HIV infection were referred for
      outpatient HIV counseling and testing at our institution within one week. This
      study was divided into three study periods. During the first and third periods,
      no financial incentive was offered for completing HIV counseling and testing.
      During the second period, a 25 dollars incentive was offered for completing HIV
      counseling and testing. RESULTS: During the study, 372 patients were referred for
      HIV counseling and testing. During the control periods, 20 (8%) of 252 patients
      completed HIV counseling and testing; during the intervention period, 27 (23%) of
      120 patients completed HIV counseling and testing (odds ratio, 3.4; 95%
      confidence interval = 1.8 to 6.3). Of the 47 patients who completed HIV
      counseling and testing, none (0%; 95% confidence interval = 0% to 8%) tested
      positive for HIV infection. CONCLUSIONS: The use of a modest financial incentive
      increased the proportion of patients who completed HIV counseling and testing
      after being referred from the ED. It is unclear whether the use of a financial
      incentive increases the identification of HIV-infected patients unaware of their
      status or if it is cost-effective.

PMID- 15995094
TI  - Competence of new emergency medicine residents in the performance of lumbar
      punctures.
AB  - BACKGROUND: Medical students are taught some procedural skills during medical
      school, but there is no uniform set of procedures that all students learn before
      residency. OBJECTIVE: To determine the level of competence in the performance of
      a lumbar puncture (LP) by new postgraduate year 1 (PGY1) emergency medicine (EM)
      residents. METHODS: An observational study was conducted at three EM residencies
      with 42 PGY1 residents who recently graduated from 26 various medical schools.
      The LP procedure was divided into 26 major and 44 minor steps to create a scoring
      protocol. The model, procedure, and scoring protocol were validated by
      experienced emergency physicians. Subjects performed the procedure without
      interruption or feedback on an LP training model using a standard LP kit. A step
      was scored as "performed correctly" if two of the three evaluators concurred. Pre
      and poststudy questionnaires assessed subjects' prior instruction and clinical
      experience with LP, self-confidence, sense of relevance, motivation, and fatigue.
      RESULTS: Subjects completed an average of 14.8 (57%; 95% confidence interval [95%
      CI] = 53% to 61%) of the major steps (range: 4-26) and 19.1 (43%; 95% CI = 42% to
      45%) of the minor steps (range: 7-28) in 14.3 minutes (range: 3-22). Sixty-nine
      percent failed to obtain cerebrospinal fluid from the model. Subjects' levels of
      confidence changed slightly on a five-point scale from 2.8 ("little-to-some")
      before the test to 2.5 after the test. Eighty-three percent of the subjects
      previously performed LPs on patients during medical school (average attempts =
      2.2; range: 0-10), but only 40% of those who did so were supervised by an
      attending during their first attempt. CONCLUSIONS: In the cohort studied, new
      PGY1 EM residents had not attained competence in performing LPs from training in
      medical school. Most new PGY1 residents probably require training, practice, and
      close, direct supervision of this procedure by attending physicians until the
      residents demonstrate competent performance.

PMID- 15995095
TI  - Overnight and postcall errors in medication orders.
AB  - OBJECTIVE: To compare the error rates in medication orders by physicians who were
      off call, on overnight call, and postcall. METHODS: This was a retrospective
      review of inpatient medication orders, pharmacy records, and resident physician
      work schedules in a university-affiliated community teaching hospital with
      residency programs in emergency medicine, family practice, internal medicine,
      obstetrics, pediatrics, and surgery. The authors calculated error rates, odds
      ratios (ORs), and 95% confidence intervals (95% CIs) for physicians during April
      2000. RESULTS: In 8,195 medication orders, there were 177 errors (2.16% overall
      error rate). There was an increased error rate for overnight and postcall orders
      (2.71%, OR 1.44, 95% CI = 1.06 to 1.95) in comparison to orders written by off
      call physicians (1.90%). Error rates were significantly higher on the
      medical/surgical wards during the overnight (3.91%, OR 1.89, 95% CI = 1.22 to
      2.92) and postcall (3.41%, OR 1.64, 95% CI = 1.10 to 2.43) periods compared with
      the off-call (2.11%) period, and postgraduate year 1 (PGY1) physicians had a
      higher overnight error rate (4.23%, OR 2.28, 95% CI = 1.44 to 3.61). Error rates
      were also higher on the medical/surgical wards compared with critical care units
      (2.62% vs. 1.22%, OR 2.17, 95% CI = 1.48 to 3.18). The PGY1 physicians had error
      rates similar to those of the PGY2-5 physicians when off call, but were
      significantly higher on overnight call (4.23% vs. 0.52%, OR 8.47, 95% CI = 2.00
      to 35.82). CONCLUSIONS: Medication-ordering error rates were higher for overnight
      and postcall physicians, particularly on the general medical/surgical wards, and
      in PGY1 physicians during the overnight period.

PMID- 15995096
TI  - Does simulator training for medical students change patient opinions and
      attitudes toward medical student procedures in the emergency department?
AB  - OBJECTIVES: To determine how simulator training impacts patients' preferences
      about medical student procedures in the emergency department. METHODS: A
      questionnaire was administered to a convenience sample of 151 of 185 patients
      approached (82% participation) seen in the emergency department of a midwestern
      teaching hospital. The questionnaire asked how many procedures they would prefer
      a medical student have performed after mastering the procedure on a simulator
      before allowing the medical student to perform this procedure on them. The
      procedures included venipuncture, placement of an intravenous line, suturing the
      face or arm, performing a lumbar puncture, placement of a central line, placement
      of a nasogastric tube, intubation, and cardioversion. These results were compared
      with those of a similar study asking about the same procedures without the
      stipulation that the skill had been mastered on a simulator. RESULTS: A high of
      57% (venipuncture) and a low of 11% (placement of a central line) would agree to
      be a student's first procedure after simulator training. Except for intubating
      and suturing, participants were more likely (p < 0.05) to allow a medical student
      to perform a procedure on them after simulator training than without simulator
      training. Many patients prefer not to have a medical student perform a procedure
      no matter how many procedures the student has done (low of 21% for venipuncture,
      high of 55% for placement of a central line). CONCLUSIONS: Patients are more
      accepting of medical students performing procedures if the skill has been
      mastered on a simulator. However, many patients do not want a medical student to
      perform a procedure on them regardless of the student's level of training.

PMID- 15995097
TI  - HIV postexposure prophylaxis in sexual assault: current practice and patient
      adherence to treatment recommendations in a large urban teaching hospital.
AB  - BACKGROUND: Although rare, HIV transmission is one of the most feared
      consequences of sexual assault. While availability of medications to prevent HIV
      transmission (HIV nonoccupational postexposure prophylaxis [HIV nPEP]) is
      increasing, little is known about emergency department (ED) prescribing practices
      and patient adherence to treatment recommendations. OBJECTIVES: To determine
      factors associated with offering, following up with, and adhering to treatment
      when HIV nPEP is initiated for sexual assault victims. METHODS: This was a
      retrospective chart review of female patients presenting with complaint of sexual
      assault to an urban ED from October 1, 1999, to September 30, 2002. HIV nPEP
      medications and/or follow-up were provided without charge. Chi-square analysis
      identified factors associated with being offered or referred for nPEP and follow
      up. Variables significant at the p < 0.10 level were entered into logistic
      regression analysis. RESULTS: Two hundred twenty-nine charts were reviewed. The
      final sample size was 181. Mean age was 29.1 years; median time from assault to
      presentation was 10.1 hours; 51.5% of the assailants were known to the victims.
      HIV nPEP was offered to 89 (49%) patients, and 11 patients were referred to an
      HIV nurse. Eighty-five (85%) patients accepted, 38 of these 85 (45%) followed up,
      and 18 of the 85 (21%) completed treatment. In multivariate analysis, three
      variables were statistically significantly associated with increased likelihood
      of referral or being offered HIV nPEP: unknown assailant, having insurance, and
      younger age. Treatment was completed by 15 of 82 (18%) of ED-initiated patients,
      versus three of three (100%) referred for initiation. The authors were unable to
      identify factors associated with completing treatment. CONCLUSIONS: HIV nPEP was
      offered to less than half of sexual assault patients, and few completed
      treatment. Further studies are needed to evaluate and improve appropriateness of
      HIV nPEP administration and follow-up.

PMID- 15995098
TI  - Intensive intervention improves primary care follow-up for uninsured emergency
      department patients.
AB  - OBJECTIVES: To test an intervention designed to improve primary care use and
      decrease emergency department (ED) utilization for uninsured patients using the
      ED. METHODS: Using a randomized design, an intensive case-management intervention
      was tested with patients identified at a Level 1 urban trauma center from April
      2002 through July 2002. Following assessment in the ED, six-month follow-up data
      were gathered from four primary care sites (two Federally Qualified Health
      Centers, two hospital outpatient clinics) and two area hospitals. Eligible
      participants were uninsured, were at least 18 years of age, and did not have a
      regular primary care provider. Of 281 patients approached, 273 (97.2%) agreed to
      participate. After 42 patients were eliminated following enrollment due to
      ineligibility, there were 121 intervention and 109 comparison subjects. Health
      Promotion Advocates (HPAs) in the ED gathered information from all study
      participants. On intervention shifts, HPAs assisted patients in choosing a
      primary care provider and faxed all information to a case worker at the selected
      site. Case managers attempted to contact patients and schedule appointments. On
      comparison shifts, patients received care as usual. Primary care contact in 60
      days and subsequent ED visits in six months post-ED assessment were the main
      outcome measures. RESULTS: Intervention subjects were more likely to have a
      primary care contact (51.2% vs. 13.8%, p < 0.0001). There was no statistically
      significant difference between groups in either number of inpatient admissions or
      postintervention ED visits, although postintervention ED visits for the
      intervention group were less expensive. CONCLUSIONS: This project has
      demonstrated that it is possible to improve primary care follow-up for uninsured
      ED patients.

PMID- 15995099
TI  - Impact of a transfer center on interhospital referrals and transfers to a
      tertiary care center.
AB  - BACKGROUND: The partnership of faculty physicians and senior clinical hospital
      administrators in the decision to accept interhospital transfers has not been
      fully studied. Transfers to academic medical centers on the basis of economics
      have been of particular concern. OBJECTIVES: To evaluate the impact of joint
      decision making on transfer acceptance, and to evaluate the basis for decisions
      to transfer patients to an academic medical center. METHODS: This was a database
      study of requested adult interhospital transfers, excluding psychiatric
      transfers, occurring between January 1, 2003, and December 31, 2003, by using
      data from a computerized patient-tracking system. Where possible, comparisons
      with the prior calendar year (i.e., prior to implementation of the administrative
      review process) were made. Incidence of refusal to accept requested transfers and
      payer mix of transfer patients were the main outcomes of interest. RESULTS: More
      than 90% of the adult patients were transferred for conditions that required
      tertiary care or met Emergency Medical Treatment and Labor Act (EMTALA)
      requirements. The patient conditions that did not meet tertiary care needs
      included obstetric patients who did not have prenatal care, patients who had hand
      and facial trauma, and patients who weighed more than 300 pounds. The payer mix
      of transfer patients remained stable when using the administrator and physician
      team to determine acceptance of transfers. During the evaluation period,
      approximately 91,500 patients statewide lost some level of Medicaid coverage.
      CONCLUSIONS: The value of an administrator and physician team as partners in the
      interhospital transfer process was demonstrated. Active management of
      interhospital transfers supports transfer of patients who require tertiary care
      or who meet EMTALA criteria, thus conserving limited bed capacity and ensuring
      financial equity, while caring for the uninsured and underinsured patients
      throughout the state.

PMID- 15995100
TI  - Profiles in patient safety: misplaced femoral line guidewire and multiple
      failures to detect the foreign body on chest radiography.
AB  - This article uses a case report and discussion to demonstrate the concept of
      active and latent failures, and the "systems approach" to the reduction of
      adverse events in medicine. The case involves an inadvertently misplaced and
      retained guidewire during femoral vein catheterization using the Seldinger
      technique, and the subsequent failure to identify the guidewire in the chest
      despite several chest radiographs and a computed tomography (CT) scan read by
      radiologists, emergency physicians, and intensivists. This event reveals active
      failures in the performance of the Seldinger technique, latent failures in the
      design of the catheter kit, and problems with the current system of
      interpretation of radiographs. The authors conclude that the design of the
      catheter kit and the Seldinger technique should be critically examined from a
      human factors standpoint and that radiographic interpretation is still heavily
      subject to human error.

PMID- 15995101
TI  - The effect of noise in the emergency department.
AB  - BACKGROUND: It is hypothesized that high ambient noise in the emergency
      department (ED) adversely affects the ability of the examiner to hear heart and
      lung sounds. OBJECTIVE: To determine the ability of various examiners to hear
      heart tones and lung sounds at the high end of loudness typically found in the ED
      setting. METHODS: The study was divided into two parts. First, sound levels in
      the ED were measured over various times during the months of January through June
      2001, using a sound level monitor. The second part of the study was the
      determination of the ability to hear heart and lung sounds on a young healthy
      volunteer using the same Littmann lightweight stethoscope at a predetermined
      ambient noise level of 90 dB. The results were entered into a database and
      analyzed using SPSS version 10 (Chicago, IL). Descriptive statistics, analysis of
      variance, frequencies, and correlation were calculated using this program.
      RESULTS: Two hundred five sound measurements were taken in the ED during the
      study period in three locations at various hours. The mean noise level at the
      nursing station was 57.60 dB, with a minimum of 45.00 dB and a maximum of 70.00
      dB. Four of the 104 test subjects (3.8%) were unable to hear the heart tones, and
      nine of the 104 (8.7%) were unable to hear the lung sounds. Fifty percent (27 of
      54) of the test subjects reported diminished lung sounds and eight of 15 (53.3%)
      reported diminished heart sounds. No significant difference was found between
      hearing heart sounds and years of experience, age, professional position, and
      quality of the sound. Significant differences were found between hearing lung
      sounds and years of experience and professional position, but not with age,
      gender, and sound quality. CONCLUSIONS: This study demonstrated that most of the
      tested examiners have the ability to hear heart and lung sounds at the extreme of
      loudness found in one ED.

PMID- 15995102
TI  - Assessing the suitability of intervention sites for quality improvement studies
      in emergency departments.
AB  - OBJECTIVES: As an initial step in disseminating an emergency department (ED)
      based quality improvement program (QIP) to improve antibiotic prescribing for
      patients with acute respiratory infections, the authors conducted a nationwide
      survey to assess the value and feasibility of the QIP. METHODS: Directors of EDs
      at 119 Veterans Administration hospitals and 160 non-Veterans Administration
      hospitals (identified based on the existence of accredited emergency medicine
      training programs and/or participation in an existing ED-based research network)
      were surveyed. The survey included questions on the current existence of an
      antibiotic QIP in the ED, enthusiasm for an antibiotic QIP program, and the
      existence of physical features in the ED that would support the QIP intervention.
      RESULTS: Overall, 77% of ED directors reported they did not have an existing
      antibiotic QIP and 84% reported they would benefit from having such a program
      (either new or in addition to their current program). In addition, 63% of
      respondents indicated that improving antibiotic prescribing was an intermediate
      to high priority in the ED. Forty-five percent reported that they did not have a
      suitable location for a key component of the intervention (an interactive
      computer kiosk), and 26% reported that they could not display educational posters
      on the walls of the examination room. CONCLUSIONS: Many EDs identify barriers to
      implementing an antibiotic QIP. Perceived and real barriers are important factors
      to consider in translating successful QIPs into routine clinical practice.

PMID- 15995103
TI  - Urine leukotriene B4 in familial Mediterranean fever and other forms of right
      lower abdominal pain.
AB  - BACKGROUND: Acute right lower abdominal pain may present a diagnostic dilemma.
      Leukotrienes have been found to be elevated in familial Mediterranean fever
      (FMF), a disease manifesting with recurrent episodes of "acute abdomen."
      OBJECTIVES: To determine whether urine leukotriene B4 (LTB4) may differentiate
      between an FMF attack and some other forms of acute right lower abdominal pain.
      METHODS: The LTB4 level was determined, using a commercial enzyme-linked
      immunosorbent assay (ELISA), in urine samples obtained from 36 patients with
      acute (< 24 hours) right lower abdominal pain presenting to the emergency
      department, and from 18 healthy volunteers. RESULTS: Compared with the healthy
      control subjects, LTB4 was significantly higher in those who had FMF (12
      patients, p < 0.03). In other forms of acute right lower abdominal pain,
      including appendicitis (eight patients), urologic disorders (eight patients), and
      nonspecific abdominal pain (eight patients), intermediate levels of LTB4 were
      observed, not significantly different from those of either FMF patients or
      healthy control subjects. CONCLUSIONS: In the samples tested, urine LTB4 levels
      were not instrumental in differentiating FMF from other acute right lower
      abdominal pain.

PMID- 15995104
TI  - GCS and QTc interval as prognostic indicators: less reliable than red clouds at
      morning for the sailor.

PMID- 15995105
TI  - Teaching evidence-based medicine.

PMID- 15995106
TI  - Comparison of soap and antibiotic solutions for irrigation of lower-limb open
      fracture wounds. A prospective, randomized study.
AB  - BACKGROUND: Irrigation of open fracture wounds is a commonly performed procedure,
      and irrigation additives have been used in an attempt to reduce the risk of
      infection. In vitro and animal studies have suggested that irrigation with
      detergent solution is more effective than irrigation with a solution containing
      antibiotic additives. This study was performed to compare the efficacy of those
      two solutions in the treatment of open fractures in humans. METHODS: Adult
      patients with an open fracture of the lower extremity were prospectively
      randomized to receive irrigation with either a bacitracin solution or a
      nonsterile castile soap solution. The patients were followed clinically to assess
      for the development of infection, healing of the soft-tissue wound, and union of
      the fracture. RESULTS: Between 1995 and 2002, 400 patients with a total of 458
      open fractures of the lower extremity were entered into the study. One hundred
      and ninety-two patients were assigned to the bacitracin group (B), and 208 were
      assigned to the castile soap group (C). Outcomes were available for 171 patients
      with a total of 199 fractures in group B and 180 patients with a total of 199
      fractures in group C. The mean duration of follow-up was 500 days. There was no
      difference between groups B and C in terms of gender, the Gustilo-Anderson grade
      of the open fracture, the time between the injury and the irrigation, smoking, or
      alcohol use. There were significant differences in the mean age (thirty-eight
      compared with forty-two years, p = 0.01), duration of follow-up (560 compared
      with 444 days, p = 0.01), prevalence of hypotension (23% compared with 14%, p =
      0.04), and duration of treatment with intravenous antibiotics (eleven compared
      with nine days, p = 0.02). An infection developed at thirty-five (18%) of the 199
      fracture sites in group B and at twenty-six (13%) of the 199 fracture sites in
      group C. This difference was not significant (p = 0.2). Bone-healing was delayed
      for forty-nine (25%) of the 199 group-B fractures and forty-six (23%) of the 199
      group-C fractures (p = 0.72). Wound-healing problems occurred in association with
      nineteen group-B fractures (9.5%) and eight group-C fractures (4%). This
      difference was significant (p = 0.03). CONCLUSIONS: Irrigation of open fracture
      wounds with antibiotic solution offers no advantages over the use of a nonsterile
      soap solution, and it may increase the risk of wound-healing problems.

PMID- 15995107
TI  - Assessment of two thoracolumbar fracture classification systems as used by
      multiple surgeons.
AB  - BACKGROUND: The reproducibility and repeatability of modern systems for
      classification of thoracolumbar injuries have not been sufficiently studied. We
      assessed the interobserver and intraobserver reproducibility of the AO
      (Arbeitsgemeinschaft fur Osteosynthesefragen) classification and compared it with
      that of the Denis classification. Our purpose was to determine whether the newer,
      AO system had better reproducibility than the older, Denis classification.
      METHODS: Anteroposterior and lateral radiographs and computerized tomography
      scans (axial images and sagittal reconstructions) of thirty-one acute traumatic
      fractures of the thoracolumbar spine were presented to nineteen observers, all
      trained spine surgeons, who classified the fractures according to both the AO and
      the Denis classification systems. Three months later, the images of the thirty
      one fractures were scrambled into a different order, and the observers repeated
      the classification. The Cohen kappa (kappa) test was used to determine
      interobserver and intraobserver agreement, which was measured with regard to the
      three basic classifications in the AO system (types A, B, and C) as well as the
      nine subtypes of that system. We also measured the agreement with regard to the
      four basic types in the Denis classification (compression, burst, seat-belt, and
      fracture-dislocation) and with regard to the sixteen subtypes of that system.
      RESULTS: The AO classification was fairly reproducible, with an average kappa of
      0.475 (range, 0.389 to 0.598) for the agreement regarding the assignment of the
      three types and an average kappa of 0.537 for the agreement regarding the nine
      subtypes. The average kappa for the agreement regarding the assignment of the
      four Denis fracture types was 0.606 (range, 0.395 to 0.702), and it was 0.173 for
      agreement regarding the sixteen subtypes. The intraobserver agreement
      (repeatability) was 82% and 79% for the AO and Denis types, respectively, and 67%
      and 56%, for the AO and Denis subtypes, respectively. CONCLUSIONS: Both the Denis
      and the AO system for the classification of spine fractures had only moderate
      reliability and repeatability. The tendency for well-trained spine surgeons to
      classify the same fracture differently on repeat testing is a matter of some
      concern.

PMID- 15995108
TI  - Percutaneous autologous bone-marrow grafting for nonunions. Influence of the
      number and concentration of progenitor cells.
AB  - BACKGROUND: Bone marrow aspirated from the iliac crest contains progenitor cells
      that can be used to obtain bone-healing of nonunions. However, there is little
      available information regarding the number and concentration of these cells that
      are necessary to obtain bone repair. The purpose of this study was to evaluate
      the number and concentration of progenitor cells that were transplanted for the
      treatment of nonunion, the callus volume obtained after the transplantation, and
      the clinical healing rate. METHODS: Marrow was aspirated from both anterior iliac
      crests, concentrated on a cell separator, and then injected into sixty
      noninfected atrophic nonunions of the tibia. Each nonunion received a relatively
      constant volume of 20 cm(3) of concentrated bone marrow. The number of progenitor
      cells that was transplanted was estimated by counting the fibroblast colony
      forming units. The volume of mineralized bone formation was determined by
      comparing preoperative computerized tomography scans with scans performed four
      months following the injection. RESULTS: The aspirates contained an average (and
      standard deviation) of 612 +/- 134 progenitors/cm(3) (range, 12 to 1224
      progenitors/cm(3)) before concentration and an average of 2579 +/- 1121
      progenitors/cm(3) (range, 60 to 6120 progenitors/cm(3)) after concentration. An
      average total of 51 x 10(3) fibroblast colony-forming units was injected into
      each nonunion. Bone union was obtained in fifty-three patients, and the bone
      marrow that had been injected into the nonunions of those patients contained
      >1500 progenitors/cm(3) and an average total of 54,962 +/- 17,431 progenitors.
      The concentration (634 +/- 187 progenitors/cm(3)) and the total number (19,324 +/
      6843) of progenitors injected into the nonunion sites of the seven patients in
      whom bone union was not obtained were both significantly lower (p = 0.001 and p <
      0.01, respectively) than those in the patients who obtained bone union. The
      volume of the mineralized callus measured at four months on the computerized
      tomography scans of the patients who had union ranged from 0.8 to 5.3 cm(3)
      (mean, 3.1 cm(3)). There was a positive correlation between the volume of
      mineralized callus at four months and the number (p = 0.04) and concentration (p
      = 0.01) of fibroblast colony-forming units in the graft. There was a negative
      correlation between the time needed to obtain union and the concentration of
      fibroblast colony-forming units in the graft (p = 0.04). CONCLUSIONS:
      Percutaneous autologous bone-marrow grafting is an effective and safe method for
      the treatment of an atrophic tibial diaphyseal nonunion. However, its efficacy
      appears to be related to the number of progenitors in the graft, and the number
      of progenitors available in bone marrow aspirated from the iliac crest appears to
      be less than optimal in the absence of concentration.

PMID- 15995109
TI  - Patellar resurfacing in total knee arthroplasty. A meta-analysis.
AB  - BACKGROUND: Patellar resurfacing during total knee arthroplasty remains
      controversial. We aimed to evaluate the effectiveness of this technique through
      an evaluation of the current literature. METHODS: We performed a meta-analysis of
      randomized controlled trials comparing total knee arthroplasties performed with
      and without patellar resurfacing. Outcomes of interest included the number of
      reoperations, the prevalence of postoperative anterior knee pain, and the
      improvement in various knee scores. RESULTS: Ten trials assessing 1223 knees were
      eligible. The absolute risk of reoperation was reduced by 4.6% (95% confidence
      interval, 1.9% to 7.3%) in the patellar resurfacing arm (between-study
      heterogeneity, p < 0.01; I(2) = 60%), implying that one would have to resurface
      twenty-two patellae (95% confidence interval, fourteen to fifty-two patellae) in
      order to prevent one reoperation. Patellar resurfacing reduced the absolute risk
      of postoperative anterior knee pain by 13.8% (95% confidence interval, 6.4% to
      21.2%), implying that one would have to resurface seven patellae (95% confidence
      interval, five to sixteen patellae) in order to prevent one case of postoperative
      anterior knee pain. Only four trials provided adequate data for a quantitative
      synthesis of the changes in the various knee scores; on the basis of those four
      trials, there was no difference in the mean improvement in the knee scores
      (standardized mean difference, 0.03; 95% confidence interval, -0.50 to 0.56).
      CONCLUSIONS: The available evidence indicates that patellar resurfacing reduces
      the risks of reoperation and anterior knee pain after total knee arthroplasty.
      The observed effects are clinically important despite their modest magnitude.
      Additional, carefully designed randomized trials are required to strengthen this
      claim.

PMID- 15995110
TI  - Diagnostic accuracy of clinical tests for the different degrees of subacromial
      impingement syndrome.
AB  - BACKGROUND: Several tests for making the diagnosis of rotator cuff disease have
      been described, but their utility for diagnosing bursitis alone, partial
      thickness rotator cuff tears, and full-thickness rotator cuff tears has not been
      studied. The hypothesis of this study was that the degree of severity of rotator
      cuff disease affects the diagnostic values of the commonly used clinical tests.
      METHODS: Eight physical examination tests (the Neer impingement sign, Hawkins
      Kennedy impingement sign, painful arc sign, supraspinatus muscle strength test,
      Speed test, cross-body adduction test, drop-arm sign, and infraspinatus muscle
      strength test) were evaluated to determine their diagnostic values, including
      likelihood ratios and post-test probabilities, for three degrees of severity in
      rotator cuff disease: bursitis, partial-thickness rotator cuff tears, and full
      thickness rotator cuff tears. A forward stepwise logistic regression analysis was
      used to determine the best combination of clinical tests for predicting the
      various grades of impingement syndrome. RESULTS: The sensitivity, specificity,
      positive predictive value, negative predictive value, and overall accuracy of the
      eight tests varied considerably. The combination of the Hawkins-Kennedy
      impingement sign, the painful arc sign, and the infraspinatus muscle test yielded
      the best post-test probability (95%) for any degree of impingement syndrome. The
      combination of the painful arc sign, drop-arm sign, and infraspinatus muscle test
      produced the best post-test probability (91%) for full-thickness rotator cuff
      tears. CONCLUSIONS: The severity of the impingement syndrome affects the
      diagnostic values of the commonly used clinical tests. The variable accuracy of
      these tests should be taken into consideration when evaluating patients with
      symptoms of rotator cuff disease.

PMID- 15995111
TI  - Supracondylar dome osteotomy for cubitus valgus deformity associated with a
      lateral condylar nonunion in children.
AB  - BACKGROUND: Open reduction, autogenous bone-grafting, and internal fixation for
      the treatment of established nonunion of the lateral condyle associated with a
      cubitus valgus deformity has a high rate of complications. As a consequence, we
      developed a new technique that includes in situ compression fixation of the
      lateral condylar nonunion and a dome-shaped supracondylar osteotomy of the distal
      aspect of the humerus through a single posterior incision. METHODS: Eight
      consecutive patients were treated with the new surgical technique between 1994
      and 2000. The mean age at the time of surgery was 8.6 years. The mean interval
      between the lateral condylar fracture and surgery was 4.9 years. The mean
      preoperative radiographic humerus-ulna angle was 31 degrees of valgus. The
      postoperative results were classified with a modification of the scoring system
      described by Dhillon et al., which assesses pain, weakness, range of motion, the
      humerus-ulna angle, and prominence of the medial epicondyle on a 12-point scale.
      RESULTS: All eight lateral condylar nonunions achieved union within three months
      postoperatively. The mean postoperative humerus-ulna angle was 5.5 degrees of
      valgus. All of the supracondylar dome osteotomies healed uneventfully, and there
      was no loss of correction postoperatively. The mean duration of follow-up was 4.5
      years. The overall results were excellent in two patients, good in four patients,
      and fair in two patients. CONCLUSIONS: With better exposure of the lateral
      condylar nonunion through a posterior approach, we can effectively stabilize the
      lateral condylar nonunion and avoid postoperative loss of motion and
      osteonecrosis of the condyle. With a dome-shaped supracondylar osteotomy, we can
      correct the cubitus valgus deformity and avoid the development of a medial
      epicondylar prominence. With careful selection of patients, this new technique
      can be an effective method to treat this clinically challenging problem.

PMID- 15995112
TI  - Vascular changes of the hand in professional baseball players with emphasis on
      digital ischemia in catchers.
AB  - BACKGROUND: Repetitive trauma to the hand is a concern for baseball players. The
      present study investigated the effects of repetitive trauma and the prevalence of
      microvascular pathological changes in the hands of minor league professional
      baseball players. In contrast to previous investigators, we documented the
      presence of abnormalities in younger, asymptomatic individuals. METHODS: Thirty
      six baseball players on active minor league rosters underwent a history and
      physical examination of both hands as well as additional specialized tests,
      including Doppler ultrasound, a timed Allen test, determination of digital
      brachial pressure indices, and ring sizing of fingers. Data were compared between
      gloved hands and throwing hands, hitters and nonhitters, and players at four
      different positions (catcher [nine subjects], outfielder [seven subjects],
      infielder [five subjects], and pitcher [fifteen subjects]). RESULTS: Digital
      brachial indices in the ring fingers of the gloved (p < 0.05) and throwing hands
      (p < 0.02) of catchers were significantly diminished compared with those in all
      other players. Doppler testing showed a significantly greater prevalence of
      abnormal flow in the ulnar artery at Guyon's canal when catchers were compared
      with other position players (p < 0.01). Doppler abnormalities were significantly
      more common in the gloved hand compared with the throwing hand (p < 0.05). Seven
      of nine catchers (and only catchers) were found to have index finger hypertrophy
      (average change, two ring sizes; p < 0.01); the hypertrophy occurred at the
      proximal phalanx and the proximal interphalangeal joint of the gloved hand.
      Catchers had a significantly higher prevalence of subjective hand symptoms
      (specifically, weakness in the gloved hand) compared with pitchers and
      infielders/outfielders (44% compared with 7% and 17%, respectively; p < 0.05).
      CONCLUSIONS: Microvascular changes are present in the hands of otherwise healthy
      professional baseball players in all positions, with a significantly higher
      prevalence in catchers, prior to the development of clinically important
      ischemia. Repetitive trauma resulting from the impact of the baseball also leads
      to digital hypertrophy in the index finger of the gloved hand of catchers. Gloves
      currently used by professional catchers do not adequately protect the hand from
      repetitive trauma.

PMID- 15995113
TI  - Range of motion of standard and high-flexion posterior stabilized total knee
      prostheses. A prospective, randomized study.
AB  - BACKGROUND: The restoration of posterior femoral translation has been shown to be
      an important factor in enhancing knee flexion after total knee arthroplasty. The
      purpose of this study was to compare the ranges of motion associated with
      standard and high-flexion posterior stabilized total knee prostheses in patients
      managed with simultaneous bilateral total knee arthroplasty. METHODS: Fifty
      patients (mean age, sixty-eight years) received a standard fixed-bearing knee
      prosthesis in one knee and a high-flexion fixed-bearing knee prosthesis in the
      contralateral knee. Two patients were men, and forty-eight were women. At a mean
      of 2.1 years postoperatively, the patients were assessed clinically and
      radiographically with use of the knee-rating systems of the Knee Society and The
      Hospital for Special Surgery. RESULTS: The mean postoperative Hospital for
      Special Surgery knee score was 90 points for the knees treated with the standard
      fixed-bearing prosthesis and 89.4 points for those treated with the high-flexion
      prosthesis. At the time of the final follow-up, the knees with the standard
      prosthesis had a mean range of motion of 135.8 degrees (range, 105 degrees to 150
      degrees ) and those with a high-flexion prosthesis had a mean range of motion of
      138.6 degrees (range, 105 degrees to 150 degrees ) (p = 0.41). No knee had
      aseptic loosening, revision, or osteolysis. CONCLUSIONS: After a minimum duration
      of follow-up of two years, we found no significant differences between the groups
      with regard to range of motion or clinical and radiographic parameters, except
      for posterior femoral condylar offset.

PMID- 15995114
TI  - Treatment of painful pseudoparesis due to irreparable rotator cuff dysfunction
      with the Delta III reverse-ball-and-socket total shoulder prosthesis.
AB  - BACKGROUND: The Delta III reverse-ball-and-socket total shoulder implant is
      designed to restore overhead shoulder function in the presence of irreparable
      rotator cuff deficiency by using the intact deltoid muscle and the stability
      provided by the prosthetic design. Our purpose was to evaluate the clinical and
      radiographic results of this arthroplasty in a consecutive series of shoulders
      with painful pseudoparesis due to irreversible loss of rotator cuff function.
      METHODS: Fifty-eight consecutive patients with moderate-to-severe shoulder pain
      and active anterior elevation of <90 degrees due to an irreparable rotator cuff
      tear were treated with a Delta III total shoulder replacement at an average age
      of sixty-eight years. Seventeen of the procedures were the primary treatment for
      the shoulder, and forty-one were revisions. The patients were examined clinically
      and radiographically after an average duration of follow-up of thirty-eight
      months. RESULTS: On the average, the subjective shoulder value increased from 18%
      preoperatively to 56% postoperatively (p < 0.0001); the relative Constant score,
      from 29% to 64% (p < 0.0001); the Constant score for pain, from 5.2 to 10.5
      points (p < 0.0001); active anterior elevation, from 42 degrees to 100 degrees (p
      < 0.0001); and active abduction, from 43 degrees to 90 degrees (p < 0.0001). The
      patients for whom the implantation of the Delta III prosthesis was the primary
      procedure and those who had had previous surgery showed similar amounts of
      improvement. The total complication rate, including all minor complications, was
      50%, and the reoperation rate was 33%. Of the seventeen primary operations, 47%
      (eight) were associated with a complication and 18% (three) were followed by a
      reoperation. Of the forty-one revisions, 51% (twenty-one) were associated with a
      complication and 39% (sixteen) were followed by a reoperation. Subjective results
      and satisfaction rates were not influenced by complications or reoperations when
      the prosthesis had been retained. CONCLUSIONS: Total shoulder arthroplasty with
      the Delta III prosthesis is a salvage procedure for severe shoulder dysfunction
      caused by an irreparable rotator cuff tear associated with other glenohumeral
      lesions. Complications were frequent following both primary and revision
      procedures, but they rarely affected the final outcome. The procedure has a
      substantial potential to improve the condition of patients with severe shoulder
      dysfunction, at least in the short term.

PMID- 15995115
TI  - Prevalence of primary and revision total hip and knee arthroplasty in the United
      States from 1990 through 2002.
AB  - BACKGROUND: The purpose of this study was to quantify the procedural rate and
      revision burden of total hip and knee arthroplasty in the United States and to
      determine if the age or gender-based procedural rates and overall revision burden
      are changing over time. METHODS: The National Hospital Discharge Survey (NHDS)
      for 1990 through 2002 was used in conjunction with United States Census data to
      quantify the rates of primary and revision arthroplasty as a function of age and
      gender within the United States with use of methodology published by the American
      Academy of Orthopaedic Surgeons. Poisson regression analysis was used to evaluate
      the procedural rate and to determine year-to-year trends in primary and revision
      arthroplasty rates as a function of both age and gender. RESULTS: Both the number
      and the rate of total hip and knee arthroplasties (particularly knee
      arthroplasties) increased steadily between 1990 and 2002. Over the thirteen
      years, the rate of primary total hip arthroplasties per 100,000 persons increased
      by approximately 50%, whereas the corresponding rate of primary total knee
      arthroplasties almost tripled. The rate of revision total hip arthroplasties
      increased by 3.7 procedures per 100,000 persons per decade, and that of revision
      total knee arthroplasties, by 5.4 procedures per 100,000 persons per decade.
      However, the mean revision burden of 17.5% for total hip arthroplasty was more
      than twice that for total knee arthroplasty (8.2%), and this did not change
      substantially over time. CONCLUSIONS: The number and prevalence of primary hip
      and knee replacements increased substantially in the United States between 1990
      and 2002, but the trend was considerably more pronounced for primary total knee
      arthroplasty. CLINICAL RELEVANCE: The reported prevalence trends have important
      ramifications with regard to the number of joint replacements expected to be
      performed by orthopaedic surgeons in the future. Because the revision burden has
      been relatively constant over time, we can expect that a greater number of
      primary replacements will result in a greater number of revisions unless some
      limiting mechanism can be successfully implemented to reduce the future revision
      burden.

PMID- 15995116
TI  - Body mass index as a predictor of complications after operative treatment of
      acetabular fractures.
AB  - BACKGROUND: Obesity, a growing public health concern, is often thought to be an
      important risk factor for postoperative complications. We hypothesized that body
      mass index is predictive of complications after operative treatment of acetabular
      fractures. METHODS: A retrospective chart review identified 169 consecutive
      patients in whom an acetabular fracture had been treated with open reduction and
      internal fixation at a level-1 trauma center. The patients were stratified into
      four classes according to their body mass index: normal (<25), overweight (> or
      =25 but <30), obese (> or =30 but <40), and morbidly > or =40). The perioperative
      outcomes that were evaluated included estimated blood loss, wound infection,
      nerve palsy, deep venous thrombosis, pulmonary embolism, and heterotopic
      ossification. Multivariate general linear models were used to test for the
      relationship between body mass index and perioperative outcomes while controlling
      for potential intervening variables (including surgical approach, fracture type,
      and surgeon experience). Odds ratios were calculated as well. RESULTS: When body
      mass index was measured as a continuous variable, it was found to have a
      significant relationship with estimated blood loss (p = 0.003), prevalence of
      wound infection (p = 0.002), and prevalence of deep venous thrombosis (p = 0.03).
      Odds ratio analysis revealed that obese subjects (body mass index of > or =30)
      were 2.1 times more likely than patients of normal weight (body mass index of
      <25) to have an estimated blood loss of >750 mL and 2.6 times more likely to have
      a deep venous thrombosis. Morbidly obese patients (body mass index of > or =40)
      were five times more likely to have a wound infection. CONCLUSIONS: Body mass
      index is predictive of complications after operative treatment of acetabular
      fractures.

PMID- 15995117
TI  - Corrective osteotomy for intra-articular malunion of the distal part of the
      radius.
AB  - BACKGROUND: Corrective osteotomy is an appealing treatment for malunited
      articular fractures of the distal part of the radius since articular incongruity
      may be the factor most strongly associated with arthrosis and diminished function
      after such fractures. Enthusiasm for osteotomy has been limited by concerns
      regarding the difficulty of the technique and the potential for additional
      injury, osteonecrosis, and nonunion. METHODS: Twenty-three skeletally mature
      patients were evaluated at an average of thirty-eight months after corrective
      osteotomy for an intra-articular malunion of the distal part of the radius. The
      indication for the osteotomy included dorsal or volar subluxation of the
      radiocarpal joint in fourteen patients and articular incongruity of > or =2 mm as
      measured on a posteroanterior radiograph in seventeen patients. Six patients had
      combined intra-articular and extra-articular malunion. The average interval from
      the injury to the osteotomy was six months. The average maximum step-off or gap
      of the articular surface prior to the operation was 4 mm. RESULTS: One patient
      had a subsequent partial wrist arthrodesis because of radiocarpal arthrosis, and
      three patients had additional surgery because of dysfunction of the distal
      radioulnar joint. One patient had a rupture of the extensor pollicis longus,
      which was treated with a tendon transfer. The final articular incongruity
      averaged 0.4 mm, and the final grip strength averaged 85% of that on the
      contralateral side. The rate of excellent or good results was 83% according to
      the rating systems of Fernandez and of Gartland and Werley, and 43% according to
      a modification of the rating system of Green and O'Brien. CONCLUSIONS: The
      results of corrective osteotomy for the treatment of intra-articular malunion are
      comparable with those of osteotomy for the treatment of extra-articular malunion.
      Intra-articular osteotomy can be performed with acceptable safety and efficacy,
      it improves wrist function, and it may help to limit the need for salvage
      procedures such as partial or total wrist arthrodesis.

PMID- 15995118
TI  - Total knee arthroplasty in juvenile rheumatoid arthritis.
AB  - BACKGROUND: There is a paucity of reports regarding the long-term results of
      total knee arthroplasty in patients with juvenile rheumatoid arthritis. The
      purpose of this study was to evaluate the outcome of total knee arthroplasty in
      patients with juvenile rheumatoid arthritis who had been followed for a minimum
      of twelve years. METHODS: Eight consecutive patients (fifteen knees) with
      juvenile rheumatoid arthritis underwent total knee arthroplasty at an average age
      of 16.8 years. Clinical evaluation of pain status, range of motion, and the
      ability to walk and radiographic evaluation of the alignment of the knees and
      component loosening were performed preoperatively and at a mean of 15.5 years
      postoperatively. RESULTS: All patients had substantial pain and functional
      limitation before the surgery, and seven of the eight patients used a wheelchair.
      At the time of the latest follow-up, which was after revision surgery in three
      patients, all of the knees were pain-free and six patients were able to walk
      about the community. The mean arc of motion had increased from 36 degrees to 79
      degrees . The final radiographic evaluation showed that thirteen of the fifteen
      knees were in neutral alignment and two were in valgus. Failure, defined as
      revision of any of the components or definite loosening as seen radiographically,
      occurred in three knees. CONCLUSIONS: Good results, in terms of pain relief and
      restoration of function, were seen at a minimum of twelve years following total
      knee arthroplasty in our series of patients with juvenile rheumatoid arthritis.
      This procedure is a reasonable option when nonoperative therapy has been
      inadequate for patients with severe disability and pain in this relatively young
      population.

PMID- 15995119
TI  - Early osteolysis following second-generation metal-on-metal hip replacement.
AB  - BACKGROUND: Total hip arthroplasty with use of metal-on-metal bearings has been
      reintroduced as an alternative to the use of metal-on-polyethylene bearings
      because of theoretical advantages such as reduced wear and a lower prevalence of
      osteolysis. However, we observed early osteolysis in a cohort of patients who had
      been managed with second-generation metal-on-metal hip replacements and
      investigated the possible etiologic role of metal hypersensitivity. METHODS: We
      retrospectively analyzed 165 patients (169 hips) who had undergone primary
      cementless total hip replacement with a contemporary metal-on-metal total hip
      design between 2000 and 2002. After a minimum duration of follow-up of twenty
      four months, nine patients (ten hips) had an osteolytic lesion localized to the
      greater trochanter. Skin-patch tests for hypersensitivity to metals were
      performed on the nine patients and on nine randomly selected patients with total
      hip replacements who did not have osteolytic changes and who were matched to the
      study cohort for age and gender. Microbiological cultures, histopathologic
      examinations, and immunohistochemical analysis were performed on samples of
      periprosthetic tissue that were collected during revision arthroplasty on two
      hips with early osteolysis. RESULTS: The patients with early osteolysis had a
      significantly higher rate of hypersensitivity reaction to cobalt compared with
      controls (p = 0.031). The retrieved periprosthetic tissues showed no evidence of
      metallic staining, but histologic analysis revealed a perivascular accumulation
      of CD3-positive T-cells and CD68-positive macrophages and an absence of both
      particle-laden macrophages and polymorphonuclear cells. Immunohistochemical
      analysis demonstrated that bone-resorbing cytokines such as IL-1beta and TNF
      alpha were produced mainly by infiltrating lymphocytes and activated macrophages.
      CONCLUSIONS: These findings raise the possibility that early osteolysis in
      patients with this second-generation metal-on-metal hip replacement is associated
      with abnormalities consistent with delayed-type hypersensitivity to metal. A
      prospective study in which a large group of patients is evaluated with multiple
      diagnostic methods is needed in order to establish whether there is a causal
      relationship between metal hypersensitivity and osteolysis.

PMID- 15995120
TI  - Effects of mechanical compression of a fibrous tissue interface on bone with or
      without high-density polyethylene particles in a rabbit model of prosthetic
      loosening.
AB  - BACKGROUND: The mechanisms leading to aseptic loosening of a total hip
      replacement are not fully understood. A fibrous tissue interface can be present
      around the implant. Hypothetically, component micromovements can compress this
      interface and cause increased fluid pressure according to biphasic models. We
      tested the hypothesis that compression of a fibrous membrane with or without the
      presence of high-density polyethylene particles leads to bone degradation.
      METHODS: A titanium implant was inserted in forty-five rabbit tibiae, and, after
      osseous integration was achieved, a fibrous tissue interface was generated. The
      animals were randomized to undergo a sham operation, treatment with compression
      of the fibrous membrane, treatment with high-density polyethylene particles, or
      treatment with both compression and particles. Morphometric analysis of the
      surrounding bone was performed on cryostat sections after Giemsa staining and
      staining of tartrate-resistant acid phosphatase activity. RESULTS: Forty
      specimens were available for analysis; five tibiae with an infection were
      excluded. After nine weeks, the controls showed vital bone, whereas the specimens
      treated with compression showed necrosis of bone and replacement of bone by
      cartilage in a discontinuous layer (p < 0.05 for both) but not fibrous tissue.
      Treatment with high-density polyethylene particles caused replacement of bone by
      fibrous tissue (p < 0.05) but not necrosis or cartilage formation. Compression
      combined with the presence of high-density polyethylene particles caused bone
      necrosis and loss of bone with replacement by cartilage and fibrous tissue (p <
      0.05). CONCLUSIONS: In this in vivo study in rabbits, fibrous membrane
      compression led to bone necrosis and cartilage formation, possibly because of
      fluid pressure or fluid flow, whereas the presence of high-density polyethylene
      particles led to the loss of bone with replacement of bone by fibrous tissue.
      Cartilage formation may be a protective response to fluid pressure and/or fluid
      flow. Fibrous membrane compression may play an important role in the early stages
      of loosening of a total hip replacement.

PMID- 15995121
TI  - Pulmonary function in adolescent idiopathic scoliosis relative to the surgical
      procedure.
AB  - BACKGROUND: The long-term pulmonary function of patients with adolescent
      idiopathic scoliosis undergoing surgical correction is uncertain. To our
      knowledge, no report has demonstrated the changes in pulmonary function five
      years or more following spinal arthrodesis with use of modern segmental spinal
      instrumentation techniques for the treatment of all types of adolescent
      idiopathic scoliosis in a similar adolescent population. METHODS: One hundred and
      eighteen patients with adolescent idiopathic scoliosis undergoing surgical
      treatment at a single institution were evaluated with pulmonary function tests to
      assess the absolute and percent-predicted value of forced vital capacity and
      forced expiratory volume in one second at the preoperative examination and at
      regular intervals postoperatively. The patients were divided into four groups
      depending upon the surgical procedure: Group 1 comprised forty-nine patients who
      had posterior spinal arthrodesis with iliac crest bone graft; Group 2, forty-one
      patients who had posterior spinal arthrodesis with thoracoplasty; Group 3,
      sixteen patients who had open anterior spinal arthrodesis with a rib resection
      thoracotomy; and Group 4, twelve patients who had combined anterior and posterior
      spinal arthrodesis with a rib resection thoracotomy and iliac crest bone graft,
      respectively. RESULTS: A comparison of absolute pulmonary function values from
      the preoperative and final follow-up evaluations demonstrated a significant (p <
      0.0001) increase in both the forced vital capacity and the forced expiratory
      volume in one second for Group 1, whereas no change was seen in those values for
      Groups 2, 3, and 4. A comparison of the changes in the percent-predicted
      pulmonary function values demonstrated significant (p < 0.05) decreases in forced
      vital capacity and forced expiratory volume in one second for Groups 2, 3, and 4,
      except for the latter value for Group 4, whereas Group 1 had no change.
      CONCLUSIONS: Patients who have had any type of chest cage disruption during the
      surgical treatment of adolescent idiopathic scoliosis demonstrate no change in
      the absolute value and a significant decline in the percent-predicted value of
      pulmonary functions at five years following surgery. Chest cage preservation is
      recommended to maximize both absolute and percent-predicted pulmonary function
      values after surgical treatment of adolescent idiopathic scoliosis.

PMID- 15995122
TI  - Diagnostic features of pelvic osteolysis on computed tomography: the importance
      of communication pathways.
AB  - BACKGROUND: Progressive periacetabular osteolysis following total hip
      arthroplasty may require revision surgery. The purpose of this study was to use
      computed tomography scans of hemipelves retrieved at autopsy from patients who
      had had a total hip arthroplasty, to define the radiographic characteristics that
      differentiate clinically important osteolytic lesions from osteoarthritic bone
      cysts. METHODS: We analyzed forty-four hemipelves that had been retrieved at
      autopsy at a mean of eight years after a total hip arthroplasty with an
      uncemented acetabular component. Computed tomography images were analyzed to
      identify the location, volume, and presence of cortical erosion and/or
      communication pathways with the joint space for all periacetabular bone defects.
      Lesions that were not present on preoperative or immediate postoperative plain
      radiographs were defined as new lesions. These new lesions were compared with
      those that were present on preoperative or immediate postoperative plain
      radiographs, which were defined as preexisting lesions. RESULTS: Forty-six
      lesions were identified on computed tomography, and sixteen of them were
      preexisting lesions. The mean volume of the preexisting lesions was 1.5 +/- 1.5
      cm(3), which was significantly smaller than the mean volume of 5.6 +/- 11.4 cm(3)
      of the thirty new lesions (p = 0.034). Twenty-eight of the thirty new lesions had
      a clear communication pathway with the joint space, while thirteen of the sixteen
      preexisting lesions demonstrated no communication pathway. New lesions were
      significantly more likely to communicate with the joint space than were
      preexisting lesions (p < 0.001). Cortical erosion was seen in sixteen of the
      thirty new lesions; none of the sixteen preexisting lesions exhibited cortical
      erosion (p < 0.001). CONCLUSIONS: The most important difference between
      osteolytic lesions and preexisting bone defects was the presence of a
      communication pathway to the joint space. Lesions that did not have an
      identifiable communication to the joint space were smaller and were not
      associated with cortical erosion. Lesions with communication to the joint through
      multiple pathways or through a central dome hole were larger and more likely to
      be associated with cortical erosion.

PMID- 15995123
TI  - Solitary epiphyseal enchondromas.
AB  - BACKGROUND: Enchondromas originating in the epiphyses of long bones are rare. The
      purpose of the present study was to evaluate the prevalence as well as the
      radiographic and clinical characteristics of epiphyseal enchondromas among
      patients who had been referred to the Armed Forces Institute of Pathology and
      Walter Reed Army Medical Center. METHODS: We performed a retrospective review of
      761 patients who had been referred to our two institutions over an approximately
      fifty-five-year period and who received a final diagnosis of enchondroma. All
      lesions had been biopsied, and the pathological diagnosis had been confirmed.
      Lesions of the hands, feet, or axial skeleton (253 patients) as well as lesions
      that appeared to originate in the metaphysis or diaphysis (475 patients) were
      excluded. Only enchondromas of the long bones that originated in the epiphysis
      were analyzed. The study group included thirty-three patients (twenty male
      patients and thirteen female patients) with a mean age of 26.7 years, including
      eleven patients with open physes. We performed additional descriptive analyses
      with regard to patient age, gender, lesion location, clinical presentation, and
      treatment as well as an extensive radiographic analysis. RESULTS: The most common
      locations were the proximal part of the humerus (ten lesions; 30%) and the distal
      part of the femur (six lesions; 18%). The most common presenting symptom was pain
      (twenty-three patients). Radiographic analysis demonstrated extensive matrix
      mineralization in association with twenty-three lesions. Twenty-eight of the
      thirty-three lesions were geographically well defined; of these, twenty-one had
      sclerotic borders, and seven did not. Although all lesions were centered and were
      predominantly located within the epiphysis, twenty of the thirty-three lesions
      demonstrated radiographic evidence of metaphyseal extension, including four of
      the eleven lesions in patients with open physes. Twenty-four lesions extended
      into the subchondral bone. The mean size of the thirty-three enchondromas in
      greatest radiographic dimension was 2.7 cm (range, 1.1 to 4.9 cm). Twenty-six of
      the thirty-three lesions were amenable to surgical treatment with curettage with
      or without bone-grafting, with only one recurrence. With the limited follow-up
      available, no lesion underwent sarcomatous degeneration. CONCLUSIONS: Epiphyseal
      enchondromas are rare lesions. Although their biologic behavior appears to mirror
      that of conventional metaphyseal enchondromas, their proximity to the joint space
      may lead to more frequent painful symptoms, a propensity for physeal involvement,
      and the need for earlier definitive surgical intervention.

PMID- 15995124
TI  - Comprehensive treatment of late-onset tibia vara.
AB  - BACKGROUND: Late-onset tibia vara (Blount disease) can be difficult to treat
      because of frequent morbid obesity and associated deformities, including distal
      femoral varus, proximal tibial procurvatum, and distal tibial valgus, that
      contribute to lower extremity malalignment. We present a comprehensive approach
      that addresses all components of the deformity and allows restoration of the
      anatomic and mechanical axes. METHODS: Fifteen consecutive patients (nineteen
      lower extremities) with late-onset tibia vara were managed with this
      comprehensive approach. The mean age of the patients at the time of surgery was
      14.9 years, and the mean weight was 113 kg. Standing anteroposterior and lateral
      radiographs were made preoperatively and at the time of the final follow-up.
      Preoperatively, the mean mechanical axis deviation was 108 mm, the mean lateral
      distal femoral angle was 95 degrees , and the mean mechanical medial proximal
      tibial angle was 71 degrees . In all nineteen extremities, the proximal tibial
      varus deformity was corrected by means of a valgus osteotomy and application of
      an Ilizarov ring external fixator. Distal femoral varus was corrected by means of
      either hemiepiphyseal stapling or valgus osteotomy with blade-plate fixation in
      thirteen of the nineteen extremities. Distal tibial valgus was treated either
      with hemiepiphyseal stapling or with varus osteotomy and gradual correction with
      use of the Ilizarov external fixator in eleven of the nineteen extremities.
      RESULTS: After a mean duration of follow-up of 5.0 years, the mean mechanical
      axis deviation had improved to 1 mm (range, 20 to -30 mm), the lateral distal
      femoral angle had improved to 87 degrees (range, 83 degrees to 98 degrees), and
      the mechanical medial proximal tibial angle had improved to 88 degrees (range, 83
      degrees to 98 degrees ). The mean time required for correction of the proximal
      tibial varus deformity was thirty-one days, and the external fixator was removed
      at a mean of 4.5 months postoperatively. All patients had development of one or
      more superficial pin-track infections (mean, 1.9 pin-site infections per
      patient). No wound infections, nonunions, or neurovascular complications
      occurred. Eighteen of the nineteen extremities were pain-free at the time of the
      final follow-up. CONCLUSIONS: This comprehensive approach allowed restoration of
      the mechanical and anatomic axes of the lower extremity in patients with late
      onset tibia vara, resulting in a resolution of symptoms as a result of
      normalization of the weight-bearing forces across the knee and ankle. We believe
      that this approach will decrease the risk of early degenerative arthritis of the
      knee.

PMID- 15995125
TI  - Posterolateral rotatory instability of the elbow following radial head resection.
AB  - BACKGROUND: Resection is a common procedure for the treatment of comminuted
      fractures of the radial head. While radial head resection is associated with a
      high success rate when performed for appropriate indications, a number of well
      defined biomechanical complications have been reported following this procedure,
      including proximal migration of the radius, the development of valgus deformity,
      and recurrent elbow instability in the acute setting. However, posterolateral
      rotatory instability has not previously been recognized as a complication of
      radial head resection. While the absence of the radial head makes the diagnosis
      difficult, we have identified a series of patients with posterolateral rotatory
      instability following radial head resection. We believe that this instability is
      secondary to unrecognized lateral ulnar collateral ligament deficiency. METHODS:
      Between November 1995 and September 2000, forty-two patients were evaluated
      because of elbow or forearm complaints following radial head resection. Seven
      patients (17%) were diagnosed with posterolateral rotatory instability on the
      basis of characteristic clinical and radiographic findings. RESULTS: The study
      group included five men and two women with a mean age of forty-two years. All
      seven patients had had radial head excision for the treatment of a comminuted
      radial head fracture at a mean of forty-four months (range, four months to
      sixteen years) prior to referral. All seven patients had lateral elbow pain, a
      sense of instability and/or weakness, and a positive lateral pivot-shift test.
      Posterolateral rotatory instability secondary to lateral ulnar collateral
      ligament insufficiency was confirmed intraoperatively in the four patients who
      were managed surgically. CONCLUSIONS: Clinicians should be aware that
      posterolateral rotatory instability may be a cause of unexplained elbow pain and
      instability following radial head resection. This diagnosis has implications for
      the prevention and treatment of this condition.

PMID- 15995126
TI  - Sympathetic and sensory neural elements in the tendon of the long head of the
      biceps.
AB  - BACKGROUND: Although the tendon of the long head of the biceps is a well-known
      source of shoulder pain, the pathophysiological basis of this pain has yet to be
      explained. The aim of this study was to detect and characterize any nervous
      element of the tendon and to determine a possible explanation for pain
      originating from this structure. METHODS: The nature of the neuronal innervation
      of the tendon of the long head of the biceps was studied immunohistochemically,
      in four tendons from different human cadavers, with use of neurofilament antibody
      2H3, neurofilament-like antibody 3A10, calcitonin gene-related peptide, substance
      P, and tyrosine hydroxylase. RESULTS: A large neuronal network, asymmetrically
      distributed along the length of the tendon with a higher degree of innervation at
      the tendon origin, was identified by the neurofilament and neurofilament-like
      antibodies 2H3 and 3A10. This innervation was found to be positive for calcitonin
      gene-related peptide and substance P, suggesting the presence of thinly
      myelinated or unmyelinated sensory neurons. It was also positive for tyrosine
      hydroxylase, suggesting a post-ganglionic sympathetic origin. CONCLUSIONS AND
      CLINICAL RELEVANCE: These findings demonstrate that the tendon of the long head
      of the biceps is innervated by a network of sensory sympathetic fibers, which may
      play a role in the pathogenesis of shoulder pain.

PMID- 15995127
TI  - Congenital absence of the long head of the biceps tendon. A case report.

PMID- 15995128
TI  - Atlantoaxial rotatory dislocation with hypoglossal nerve palsy in a patient with
      ankylosing spondylitis. A case report.

PMID- 15995129
TI  - Supracondylar femoral fracture after arthroscopic reconstruction of the anterior
      cruciate ligament. A case report.

PMID- 15995130
TI  - Combined posterior and convergent elbow dislocations in an adult. A case report
      and review of the literature.

PMID- 15995131
TI  - Congenital unilateral posteromedial bowing of the tibia and fibula: insights
      regarding pathogenesis from prenatal pathology. A case report.

PMID- 15995132
TI  - Upper extremity compartment syndrome secondary to acquired factor VIII inhibitor.
      A case report.

PMID- 15995133
TI  - Bisphosphonates in orthopaedic surgery.
AB  - Bisphosphonates are the most clinically important class of antiresorptive agents
      available to treat diseases characterized by osteoclast-mediated bone resorption.
      Currently, seven bisphosphonates have the approval of the United States Food and
      Drug Administration. The most common adult diseases treated with bisphosphonates
      include osteoporosis, Paget disease, and metastatic bone disease. The treatment
      of pediatric disorders such as osteogenesis imperfecta and fibrous dysplasia with
      bisphosphonates has gained momentum, and initial investigations have demonstrated
      an acceptable safety profile. Currently, there is a lack of long-term follow-up
      data, which will be necessary for the development of responsible guidelines for
      therapy.

PMID- 15995134
TI  - Does sex matter in musculoskeletal health? The influence of sex and gender on
      musculoskeletal health.

PMID- 15995135
TI  - Nothing about you...without you.

PMID- 15995136
TI  - The human form: accepting the prioritization of patient values.
AB  - A seventeen-year-old boy who had had a subtotal femoral reconstruction because of
      an osteosarcoma in the left femur, and a subsequent revision for hardware
      failure, was again having severe pain secondary to failure of the endoprosthesis.
      The patient's original orthopaedic oncologist, who had performed both previous
      operations, recommended that the patient have an above-the-knee amputation. The
      patient and his parents inquired about the Van Nes rotationplasty. They were told
      directly that it was an antiquated procedure that was not done anymore. The
      prosthetist with whom they were working gave them the name of an orthopaedic
      oncologist who could perform the Van Nes procedure. They traveled 850 miles for a
      consultation, and the patient underwent the procedure. Several months after the
      operation, the patient walked with a slight limp and looked like a perfectly
      normal teenager in a pair of jeans. On examination, he had a well-fitted below
      the-knee prosthesis attached to his foot, which was in nearly 160 degrees of what
      was essentially plantar flexion, perfectly matching the attitude of a knee as it
      couples to a below-the-knee prosthesis. The boy and his parents, who had decided
      months earlier to opt for an uncommonly performed procedure that would give him a
      chance at a "normal" appearing and functioning limb, deemed the surgery a
      complete success with an "excellent" outcome.

PMID- 15995137
TI  - What's new in adult reconstructive knee surgery.

PMID- 15995138
TI  - Immunohistochemical determination of cytosolic cytochrome C concentration in
      cardiomyocytes.
AB  - Cytochrome c release from the intermembrane space of mitochondria is one of the
      triggers of apoptosis. There is no histochemical method available to demonstrate
      cytochrome c in cryostat sections, possibly because small cytosolic proteins
      diffuse readily into aqueous fixation media. This report shows that it is
      possible to demonstrate cytochrome c release in cardiomyocytes in failing
      myocardium using vapor fixation of cryostat sections and immunohistochemistry.
      The method is calibrated using sections from gelatin blocks containing known
      concentrations of cytochrome c. The method is applied to the hypertrophied right
      ventricular wall of rats in which pulmonary hypertension was induced by
      monocrotaline. Cytochrome c release is found in a fraction of the cardiomyocytes,
      leading to a mosaic-staining pattern. Cytochrome c release was found in myocytes
      over the full range of cross-sectional area (from 1 to 3.9 times control) in the
      hypertrophied myocardium. Cytosolic cytochrome c concentrations up to 0.4-0.5 mM
      occur frequently.

PMID- 15995139
TI  - A mapping study of caspase-3 activation following acute spinal cord contusion in
      rats.
AB  - Spinal cord injury (SCI) initiates a cascade of biochemical changes that results
      in necrotic and apoptotic cell death. There is evidence that caspase-3 activation
      and apoptotic cell death occur within hours after SCI. However, the time course
      and cellular localization of activated caspase-3 has not been examined. Such
      information is essential because caspase-3-independent apoptotic pathways do
      exist. In this experiment, we describe the distribution of and cell types
      containing activated caspase-3 at 4 hr, 1 day, 2 days, 4 days, and 8 days
      following SCI in rats. Numerous caspase-3-positive cells were observed at 4 hr
      and 1 day postinjury and colocalized most often with CC1, a marker for
      oligodendroglia. Both markers disappeared near the injury epicenter over the next
      several days. Activated caspase-3 was again present in the injured spinal cord on
      postoperative day 8, which coincided with a reemergence of CC1-positive cells.
      Many of these CC1-positive cells again colocalized activated caspase-3. NeuN
      positive neurons of the dorsal horn were occasionally immunopositive for
      activated caspase-3 at early time points. OX42-positive microglia/macrophages
      rarely contained activated caspase-3. The results indicate a biphasic pattern of
      caspase-3 activation during the first 8 days postinjury, suggesting that at least
      two mechanisms activate caspase-3 following SCI. This time-course study provides
      a framework for investigating and understanding the different signaling events
      contributing to this biphasic pattern of caspase-3 activation.

PMID- 15995140
TI  - Light and electron microscopic immunohistochemical detection of bromodeoxyuridine
      labeled cells in the brain: different fixation and processing protocols.
AB  - Bromodeoxyuridine (BrdU) immunohistochemistry is the method of choice for
      labeling newly generated cells in the brain. Most BrdU studies utilize
      paraformaldehyde-fixed brain tissue because of its compatibility with both BrdU
      and other immunohistochemical methods. However, stronger fixation is required for
      electron microscopic studies, and unfixed tissue is needed for biochemical and
      molecular studies. Because there are no systematic studies comparing the effects
      of different fixatives on BrdU immunohistochemistry in brain tissue, we compared
      BrdU immunohistochemical methods in brain tissue fixed with 4% paraformaldehyde,
      a mixed glutaraldehyde-paraformaldehyde fixative for electron microscopy, and
      unfixed tissue from brains perfused only with buffer and flash frozen. After
      optimizing immunostaining protocols, qualitative assessments of light microscopic
      diaminobenzidine labeling and of double-label immunofluorescence with confocal
      microscopy demonstrated excellent BrdU labeling in each of the three groups.
      Quantitative stereological assessment of the number of BrdU-labeled cells in rat
      dentate gyrus showed no significant difference in the number of labeled cells
      detected with each perfusion protocol. Additionally, we developed a protocol to
      visualize BrdU-labeled cells in the electron microscope with adequate
      preservation of fine structure in both rat and monkey brain.

PMID- 15995141
TI  - Three-dimensional imaging of the intracellular localization of growth hormone and
      prolactin and their mRNA using nanocrystal (Quantum dot) and confocal laser
      scanning microscopy techniques.
AB  - Semiconductor nanocrystals (Quantum dots, Qdots) have recently been used in
      biological research, because they do not fade on exposure to light, and they
      enable us to obtain multicolor imaging because of a narrow emission peak that can
      be excited via a single wavelength of light. There have been no reports of
      simultaneous localization of mRNA and protein using Qdots. We successfully
      applied these advantages of Qdot and confocal laser scanning microscopy (CLSM) to
      three-dimensional images of the intracellular localization of growth hormone and
      prolactin and to their mRNA. In situ hybridization and immunohistochemistry using
      Qdots combined with CLSM can optimally illustrate the relationship between
      protein and mRNA simultaneously in three dimensions. Such an approach enables us
      to visualize functional images of proteins in relation with mRNA synthesis and
      localization.

PMID- 15995142
TI  - Cardiomyocyte remodeling and sarcomere addition after uniaxial static strain in
      vitro.
AB  - Individual cardiomyocytes are lengthened in dilated cardiomyopathy. However, it
      is not known how the new sarcomeres are added to preexisting myofibrils. Using a
      three-dimensional microtextured culturing system, a 10% mechanical static strain
      was applied to aligned, well-attached cardiomyocytes from neonatal rat. The
      morphology of the myofibrils and the ends of the myocytes were examined.
      Disruptions of the sarcomeric pattern for actin showed a progression from weak to
      intense staining over 4 hr. The lightly stained sarcomeres were common at 1 hr
      after being strained, peaked at 2 hr, and then subsided. In contrast, the numbers
      of intensely stained sarcomeres were initially low, peaked at 3 hr, and then
      began to decline when compared with control values. The myocyte ends showed
      elongations and convolutions after 3 hr and 4 hr of mechanical strain when
      observed with alpha-actinin and N-cadherin staining. We suggest that myocytes
      from neonatal rat hearts remodel by insertion of new sarcomeres throughout the
      cell length and also by enhancement at the intercalated discs.

PMID- 15995143
TI  - Cardiomyocytes of chronically ischemic pig hearts express the MDR-1 gene-encoded
      P-glycoprotein.
AB  - The multidrug-resistant (MDR)-1 gene-encoded P-glycoprotein (Pgp-170) is not
      normally present in the cardiomyocyte. Given that in other tissues Pgp-170 is not
      found under normoxic conditions but is expressed during hypoxia, we searched for
      Pgp-170 in chronically ischemic porcine cardiomyocytes. Pgp-170 was detected and
      localized via immunohistochemistry in ischemic and nonischemic cardiomyocytes of
      eight adult pigs 8 weeks after placement of an Ameroid constrictor at the origin
      of the left circumflex artery (Cx). Regional myocardial ischemia in the Cx bed
      was documented with nuclear perfusion scans. Pgp-170 mass was quantified using
      Western blot analysis. In all pigs, Pgp-170 was consistently present in the
      sarcolemma and T invaginations of the cardiomyocytes of the ischemic zone. Pgp
      170 expression decreased toward the border of the ischemic zone and was negative
      in nonischemic regions as well as in the myocardium of sham-operated animals.
      Western blot analysis yielded significantly higher Pgp-170 mass in ischemic than
      in nonischemic areas. We conclude that Pgp-170 is consistently expressed in the
      cardiomyocytes of chronically ischemic porcine myocardium. Its role in the
      ischemic heart as well as in conditions such as myocardial hibernation, stunning,
      and preconditioning may have potentially relevant clinical implications and
      merits further investigation.

PMID- 15995144
TI  - Endocrine and exocrine secretion of leptin by the gastric mucosa.
AB  - Leptin is a hormone that plays important roles in nutritional status and in
      obesity. By means of immunocytochemistry, two populations of leptin-secreting
      cells were found in the lower half of the gastric mucosa. One consists of
      numerous large cells located around the gastric pits, the Chief epithelial cells,
      whereas the second refers to much smaller cells, strongly stained, few in number,
      and scattered between the gastric pits, the endocrine cells. By double
      immunostaining, leptin and pepsinogen were colocalized in the Chief cells,
      whereas the endocrine cells were positive only for leptin. Immunoelectron
      microscopy showed that leptin is present along the rough endoplasmic reticulum
      Golgi-granules secretory pathways of the Chief and endocrine cells. On the other
      hand, leptin-receptor (long and short forms) immunolabelings, although absent in
      the gastric epithelial cell plasma membranes, were present in enterocytes at the
      level of their apical and basolateral membranes. Duodenal, jejunal, and ileal
      enterocytes displayed similar labelings for the leptin receptor. Thus, exocrine
      and endocrine secretions of leptin together with the presence of leptin receptors
      on enterocyte plasma membranes constitute a gastroenteric axis that coordinates
      the role played by leptin in the digestive tract.

PMID- 15995145
TI  - Myogenic potential of muscle side and main population cells after intravenous
      injection into sub-lethally irradiated mdx mice.
AB  - Muscle side population (SP) cells have demonstrated hematopoietic and myogenic
      activities in vivo upon intravenous (IV) injection into lethally irradiated mdx
      mice. In contrast, muscle main population (MP) cells were unable to rescue the
      bone marrow of lethally irradiated mice and, consequently, their in vivo myogenic
      potential could not be assessed using this method. In the current study, muscle
      SP or MP cells derived from syngeneic wild-type male mice were delivered to sub
      lethally irradiated mdx female mice by single or serial IV injections. Recipient
      mice were euthanized 12 weeks after transplantation at which time the quadriceps
      and diaphragm muscles were analyzed for the presence of donor-derived cells. Mice
      injected with 10(4) muscle SP cells or with 10(6) MP cells appeared to have
      similar numbers of dystrophin-positive myofibers containing fused donor nuclei.
      Analysis of the remaining tissue via real-time quantitative PCR indicated that
      mice injected with muscle SP cells had a higher percentage of donor-derived Y-DNA
      in the quadriceps than mice injected with MP cells, suggesting that muscle SP
      cells may be enriched for progenitors able to engraft dystrophic skeletal muscles
      from the circulation. Although the overall engraftment did not reach
      therapeutically significant levels, these results indicate that further
      optimization of cell delivery techniques may lead to improved efficacy of cell
      mediated therapy using muscle SP cells.

PMID- 15995146
TI  - Smooth muscle-specific alpha tropomyosin is a marker of fully differentiated
      smooth muscle in lung.
AB  - Tropomyosin (Tm) is one of the major components of smooth muscle. Currently it is
      impossible to easily distinguish the two major smooth muscle (sm) forms of Tm at
      a protein level by immunohistochemistry due to lack of specific antibodies. Alpha
      sm Tm contains a unique 2a exon not found in any other Tm. We have produced a
      polyclonal antibody to this exon that specifically detects alpha-sm Tm. We
      demonstrate here the utility of this antibody for the study of smooth muscle. The
      tissue distribution of alpha-sm Tm was shown to be highly specific to smooth
      muscle. Alpha-sm Tm showed an identical profile and tissue colocalization with
      alpha-sm actin both by Western blotting and immunohistochemistry. Using lung as a
      model organ system, we examined the developmental appearance of alpha-sm Tm in
      comparison to alpha-sm actin in both the mouse and human. Alpha-sm Tm is a late
      onset protein, appearing much later than actin in both species. There were some
      differences in onset of appearance in vascular and airway smooth muscle with
      airway appearing earlier. Alpha-sm Tm can therefore be used as a good marker of
      mature differentiated smooth muscle cells. Along with alpha-sm actin and sm
      myosin antibodies, alpha-sm Tm is a valuable tool for the study of smooth muscle.

PMID- 15995147
TI  - Expression analysis of PMP22/Gas3 in premalignant and malignant pancreatic
      lesions.
AB  - PMP22 is a structural protein of Schwann cells, but it also influences cell
      proliferation. In the present study, quantitative RT-PCR (QRT-PCR) and
      immunohistochemistry were used to determine PMP22 mRNA levels and to localize
      PMP22 in the normal pancreas (n=20), chronic pancreatitis (CP) (n=22), pancreatic
      ductal adenocarcinoma (PDAC) (n=31), intraductal papillary mucinous neoplasms
      (IPMN) (n=9), mucinous cystic tumors (MCN) (n=4), and in a panel of PanIN lesions
      (n=29). PMP22 mRNA levels were significantly higher in CP (3-fold) and PDAC (2.5
      fold), compared to normal pancreatic tissues. PMP22 expression was restricted to
      nerves in the normal pancreas, while in CP and PDAC PMP22 was also expressed in
      PanIN lesions and in a small percentage of pancreatic cancer cells. PMP22 was
      weak to absent in the tumor cells of IPMNs and MCNs. PMP22 mRNA was present at
      different levels in cultured pancreatic cancer cells and up-regulated by
      transforming growth factor (TGF)-beta1 in 2 of 8 of these cell lines. In
      conclusion, PMP22 expression is present in both CP and PDAC tissues. Its
      expression in PanIN lesions and some pancreatic cancer cells in vitro and in vivo
      suggests a role of PMP22 in the neoplastic transformation process from the normal
      pancreas to pre-malignant lesions to pancreatic cancer.

PMID- 15995148
TI  - Expression of PDE11A in normal and malignant human tissues.
AB  - Cyclic nucleotide phosphodiesterase 11A (PDE11A) is the newest member in the PDE
      family. Although the tissue distribution of PDE11A mRNA has been shown, its
      protein expression pattern has not been well studied. The goal of this report is
      to investigate the distribution of PDE11A proteins in a wide range of normal and
      malignant human tissues. We utilized a polyclonal antibody that recognized all
      four PDE11A isoforms. Its specificity was demonstrated by Western blot analysis
      on a recombinant human PDE11A protein and native PDE11A proteins in various human
      tissues. Immunohistochemistry showed that PDE11A is widely expressed. Various
      degrees of immunoreactivity were observed in the epithelial cells, endothelial
      cells, and smooth muscle cells of all tissues examined. The highest expression
      was in the epithelial, endothelial, and smooth muscle cells of the prostate,
      Leydig, and spermatogenic cells of the testis, the tubule epithelial cells in the
      kidney, the epithelial and endothelial cells in the adrenal, the epithelial cells
      and macrophages in the colon, and the epidermis in the skin. Furthermore, PDE11A
      expression was also detected in several human carcinomas. Our results suggest
      that PDE11A might be involved in multiple physiological processes in various
      organs via its ability to modulate intracellular cAMP and cGMP levels.

PMID- 15995149
TI  - Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in
      different cell populations in the mouse testis.
AB  - Zinc ions play an important role in testis development and spermatogenesis. Thus,
      nutritional zinc deficiency leads to aberrant testicular development, reduced
      spermatogenesis, and male sterility. The precise actions of zinc in mediating
      these functions and the mechanisms by which zinc is itself regulated in the
      testis, however, have not been adequately elucidated. We have assessed the
      distribution of the zinc-regulating proteins ZnT-1 and metallothionein I/II (MT
      I/II) in the mouse seminiferous tubule. Co-labeling for ZnT-1 and MT I/II
      demonstrated unique patterns of distribution for these proteins, with ZnT-1
      present in Sertoli cells in addition to luminal spermatozoa and MT I/II
      restricted to spermatocytes. These findings were confirmed by dual-label
      immunofluorescence for ZnT-1 and the Sertoli cell marker, vimentin, and by
      immunoelectron microscopy. The differential expression patterns of ZnT-1 and MTs
      support the hypothesis that ZnT-1 and MTs play different roles in the regulation
      of intracellular zinc in this organ. The specific expression of ZnT-1 in the
      Sertoli cells, moreover, is consistent with their role in maintaining a
      nurturing, closely regulated environment for spermatogenesis.

PMID- 15995150
TI  - Differential intracellular distributions of inositol trisphosphate and ryanodine
      receptors within and among hematopoietic cells.
AB  - To better understand the mechanism(s) of leukocyte Ca(2+) signaling, we have
      studied the intracellular locations of two Ca(2+)-mobilizing receptors, the
      inositol 1,4,5-trisphosphate receptor and ryanodine receptor, by
      immunofluorescence microscopy. Our results show that localization differs not
      only between receptor classes within a cell, but among leukocyte types as well.
      We also illustrate the importance of preserving labile cellular filaments in
      maintaining cell integrity by fixation with the Safiejko-Mroczka and Bell
      protocol, because conventional fixation methods distort receptor patterns. We
      suggest that the observed differences influence intracellular Ca(2+) signaling.

PMID- 15995151
TI  - Communicating interdisciplinary research.

PMID- 15995152
TI  - Survivor preferences for response to IPV disclosure.
AB  - Intimate partner violence (IPV) is a major cause of health conditions among women
      presenting for health care. Many physicians and nurses miss potential
      opportunities to increase battered women's safety. The purpose of this study is
      to increase health care providers' understanding of abused women's preferences
      concerning provider response when they do disclose IPV in order to increase
      effectiveness of interventions. A total of 26 abused women from a larger study
      participated in five focus groups at three agencies on "how a hospital or
      doctor's office can be most helpful to a woman who is experiencing domestic
      violence." Women identified seven preferences for responses: (a) treat me with
      respect and concern, (b) protect me, (c) documentation, (d) give me control, (e)
      immediate response, (f) give me options, and (g) be there for me later. These
      findings indicate that women prefer an active role by health care providers when
      responding to disclosure.

PMID- 15995153
TI  - Gastric tube placement in young children.
AB  - In this study, the internal position of a nasogastric/orogastric tube was
      determined in 72 children, prior to an abdominal radiograph, by measuring CO2 and
      pH and bilirubin of tube aspirate. Fifteen of the 72 tubes (20.8%) were
      incorrectly placed on radiograph. Using the suggested adult cutoff of pH 5, pH of
      aspirate correctly predicted misplacement outside the stomach in 7/28 (25%) of
      children and correctly predicted correct placement in the stomach in 34 of 40
      children (85%). Using the suggested adult cutoff of bilirubin > or = 5 mg/dL,
      bilirubin monitoring failed to identify either of two incorrectly placed tubes.
      In this study, using an algorithm of assuming stomach placement if the pH of
      aspirate is < or = 5 and obtaining an abdominal radiograph when either no
      aspirate is obtained or the pH is >5 would have resulted in 92% accuracy.
      Alternatively, obtaining an abdominal radiograph would result in nearly 100%
      accuracy.

PMID- 15995154
TI  - Mediators of the relationship between hope and well-being in older adults.
AB  - This research examined well-being in relationship to the variables of hope,
      spirituality, and state anxiety using a cross-sectional correlation design to
      test two mediation models. The convenience sample of 130 older adults, mostly
      women, between the ages of 60 and 89, completed the Demographic Data Sheet and
      the Index of Well-Being, the Herth Hope Index, the Spiritual Perspective Scale,
      and the state anxiety portion of the State-Trait Anxiety Inventory. Statistically
      significant and positive correlations were found between hope and well-being,
      hope and spirituality, and spirituality and well-being. A statistically
      significant and negative correlation was found between hope and state anxiety and
      between state anxiety and well-being. Multiple regression analyses results
      indicated that neither spirituality nor state anxiety functioned as a mediator in
      the relationship between hope and well-being.

PMID- 15995155
TI  - Sleep disturbance and depression as barriers to adherence.
AB  - This study examined the relationships among subjective sleep disturbance,
      depressive symptoms, and adherence to medications among HIV-infected women. HIV
      infected women (N = 173) were recruited through community AIDS service
      organizations throughout South Carolina. Participants completed the Pittsburgh
      Sleep Quality Index (PSQI), the Centers for Epidemiological Studies Depression
      Scale (CES-D), and a modified version of the Adults AIDS Clinical Trials Group
      Adherence Baseline Questionnaire. Women who reported greater sleep disturbance
      also reported a higher level of depressive symptoms and reported poor adherence
      to their medication regimen. Depression helped to explain the relationship
      between sleep quality and adherence. Results indicate that assessment and
      management of sleep disturbance and depressive symptoms in women with HIV disease
      is important to promote medication adherence.

PMID- 15995156
TI  - Cytotoxic chemotherapy: new players, new tactics.
AB  - Veterinary clients often seek the same new and innovative cancer treatment
      options for their companion animals that they read about in the press or on the
      Internet. It is, therefore, necessary for the practitioner to have an
      understanding of the development of new and innovative cytotoxic drugs and
      delivery techniques. This article describes the drug development process and how
      a new product eventually finds its way into clinical use. Some of the newer drugs
      and delivery techniques applied to small animals are reviewed.

PMID- 15995157
TI  - Echocardiographic diagnosis of congenital membranous ventricular septal aneurysm
      in the dog and cat.
AB  - Membranous ventricular septal aneurysm was diagnosed by echocardiography in 17
      dogs and three cats. The aneurysm appeared as a thin membrane protruding into the
      right ventricle from the margins of a congenital ventricular septal defect (VSD).
      The aneurysm was intact in nine dogs and two cats and perforated by a small VSD
      in eight dogs and one cat. Other congenital heart defects were present in seven
      dogs. In all animals, the aneurysm was an incidental finding observed during
      echocardiographic examination, and it did not appear to directly cause any
      cardiac dysfunction.

PMID- 15995158
TI  - Influence of asparaginase on a combination chemotherapy protocol for canine
      multicentric lymphoma.
AB  - Combination chemotherapy is superior to single-agent chemotherapy for treating
      canine lymphoma, but the effect of each drug on efficacy remains unknown. By
      comparing 34 dogs treated with a modified cyclophosphamide, vincristine,
      prednisone (COP) chemotherapy protocol and 42 dogs given asparaginase in the
      induction phase of the same protocol, the effect of asparaginase on the
      chemotherapeutic protocol was determined. Both groups were compared based on
      clinical response at 2 weeks and 6 weeks, and on the progression-free interval.
      Asparaginase did not significantly increase the likelihood of a clinical
      remission or prolong the initial progression-free interval in the dogs studied.

PMID- 15995159
TI  - The use of carbon dioxide laser for the ablation of meibomian gland adenomas in
      dogs.
AB  - Twelve eyelid meibomian gland adenomas in dogs were surgically ablated using the
      carbon dioxide (CO(2)) laser. The laser site was not sutured. All procedures
      resulted in complete removal of the adenoma with no recurrences at 6 months. In
      addition, no dogs developed corneal disease secondary to the procedure, and the
      cosmetic appearance of the eyelid margins was good at the end of the 6-month
      study. Based on results of this study, CO(2) laser ablation of canine meibomian
      gland adenomas is an effective alternative to standard surgical removal.

PMID- 15995160
TI  - Outcomes of dogs presented for cataract evaluation: a retrospective study.
AB  - Two hundred and forty-four dogs were evaluated for cataracts at the University of
      Tennessee from January 2001 to December 2002. Fifty-four canine breeds were
      affected. Odds ratios for cataracts were significantly higher for six purebred
      dogs (including the cocker spaniel, miniature schnauzer, toy poodle, Boston
      terrier, miniature poodle, and bichon frise) compared with mixed-breed dogs. One
      hundred fifty-nine dogs did not have cataract surgery. The most common reason for
      dogs not having surgery was retinal degeneration (n=66).

PMID- 15995161
TI  - Soft-tissue sarcomas in dogs: a review.
AB  - Soft-tissue sarcomas are a heterogeneous group of tumors with similar biological
      behaviors. Wide surgical excision remains the cornerstone of treatment for these
      tumors. Local recurrence is common following conservative resection, and
      recurrent tumors are more difficult to treat. Radiation therapy or re-excision
      with wider margins is indicated if excision is microscopically incomplete.
      Chemotherapy is often recommended as an adjunctive treatment for high-grade soft
      tissue sarcomas because of their higher metastasis rates when compared to low-or
      intermediate-grade soft-tissue sarcomas. Knowledge of extent of disease and
      histological grade is helpful in guiding treatment choices.

PMID- 15995162
TI  - Myasthenia gravis and hypothyroidism in a dog with meningomyelitis.
AB  - A 12-year-old, spayed female miniature poodle was evaluated because of a 4-day
      history of paraparesis, dysuria, and tenesmus. Neurological assessment suggested
      peripheral nervous system dysfunction, predominantly pelvic limb weakness with a
      possible concurrent sixth lumbar (L(6)) to second sacral (S(2)) myelopathy.
      Further studies supported the diagnoses of myasthenia gravis, hypothyroidism, and
      meningomyelitis. To the authors' knowledge, this is the first reported case of
      concurrent myasthenia gravis and meningomyelitis in the dog. It was unclear
      whether the identified conditions evolved from a shared etiopathogenesis or were
      merely coincidental.

PMID- 15995163
TI  - Vascular encephalopathy associated with bacterial endocarditis in four dogs.
AB  - Vascular encephalopathy is a commonly encountered clinical complication of
      infectious endocarditis in humans, but it has been infrequently reported in dogs.
      A series of four dogs with bacterial endocarditis that subsequently developed
      acute onset of neurological deficits is described. Clinical signs, diagnostic
      test results, and outcomes for each case are presented and compared with the
      human clinical syndrome.

PMID- 15995164
TI  - Central nervous system dysfunction associated with Rocky Mountain spotted fever
      infection in five dogs.
AB  - Five dogs from the northeastern United States were presented with clinical signs
      of neurological disease associated with Rocky Mountain spotted fever (RMSF)
      infection. Four of the five dogs had vestibular system dysfunction. Other
      neurological signs included paresis, tremors, and changes in mentation. All of
      the dogs had an elevated indirect fluorescent antibody titer or a positive
      semiquantitative enzyme screening immunoassay titer for Rickettsia rickettsii at
      the time of presentation. Although a higher mortality rate has been reported for
      dogs with neurological symptoms and RMSF infection, all of the dogs in this study
      improved with appropriate medical therapy and supportive care.

PMID- 15995165
TI  - Surgical management of combined hydrocephalus, syringohydromyelia, and
      ventricular cyst in a dog.
AB  - Combined hydrocephalus, syringohydromyelia, and a ventricular cyst were found by
      magnetic resonance imaging in a 7-month-old, male miniature dachshund with gait
      abnormalities and altered mentation. Clinical signs did not improve with
      prednisone therapy. Ventriculoperitoneal shunting improved the clinical signs and
      anatomical abnormalities. Repeated operations were needed to replace the
      ventricular drainage tube at 3 and 31 months after the first surgery. The animal
      died suddenly with severe tonic-clonic, generalized seizures 3 weeks after the
      third operation. Ventriculoperitoneal shunting may be a viable treatment for
      syringohydromyelia associated with hydrocephalus.

PMID- 15995166
TI  - Nutritional myths.
AB  - Owners are sometimes confused or misinformed about nutritional facts pertaining
      to pet foods, and three common nutritional myths have been propagated in the
      popular press. The first myth is that meat by-products are of inferior quality
      compared to whole meat. The second myth is that feeding trials are unnecessary,
      and the third myth is that pet food preservatives are bad. This paper examines
      the known facts related to these three myths and discusses the importance of food
      trials and the different classes and forms of antioxidants used in pet foods.

PMID- 15995167
TI  - Thematic review series: the pathogenesis of atherosclerosis: an interpretive
      history of the cholesterol controversy, part III: mechanistically defining the
      role of hyperlipidemia.
AB  - In this third installment of the series, we point out that the absence of an
      explicit, detailed and plausible hypothesis linking hypercholesterolemia to the
      events in the artery wall was probably an important reason for continuing
      skepticism and for failure to treat elevated blood cholesterol levels. The rapid
      advances in understanding of lipoprotein metabolism in the 1950s and 1960s and
      the application of modern cellular biology in the 1970s provided the context for
      a modern consensus on pathogenetic mechanisms of atherogenesis.

PMID- 15995168
TI  - Thematic review series: The immune system and atherogenesis. Cytokine regulation
      of macrophage functions in atherogenesis.
AB  - This review will focus on the role of cytokines in the behavior of macrophages, a
      prominent cell type of atherosclerotic lesions. Once these macrophages have
      immigrated into the vessel wall, they propagate the development of
      atherosclerosis by modifying lipoproteins, accumulating intracellular lipids,
      remodeling the extracellular environment, and promoting local coagulation. The
      numerous cytokines that have been detected in atherosclerosis, combined with the
      expression of large numbers of cytokine receptors on macrophages, are consistent
      with this axis being an important contributor to lesion development. Given the
      vast literature on cytokine-macrophage interactions, this review will be
      selective, with an emphasis on the major cytokines that have been detected in
      atherosclerotic lesions and their effects on properties that are relevant to
      lesion formation and maturation. There will be an emphasis on the role of
      cytokines in regulating lipid metabolism by macrophages. We will provide an
      overview of the major findings in cell culture and then put these in the context
      of in vivo studies.

PMID- 15995169
TI  - Endostatin binds biglycan and LDL and interferes with LDL retention to the
      subendothelial matrix during atherosclerosis.
AB  - Retention of lipoproteins to proteoglycans in the subendothelial matrix (SEM) is
      an early event in atherosclerosis. We recently reported that collagen XVIII and
      its proteolytically released fragment endostatin (ES) are differentially depleted
      in blood vessels affected by atherosclerosis. Loss of collagen XVIII/ES in
      atherosclerosis-prone mice enhanced plaque neovascularization and increased the
      vascular permeability to lipids by distinct mechanisms. Impaired endothelial
      barrier function increased the influx of lipoproteins across the endothelium;
      however, we hypothesized that enhanced retention might be a second mechanism
      leading to the increased lipid content in atheromas lacking collagen XVIII. We
      now demonstrate a novel property of ES that binds both the matrix proteoglycan
      biglycan and LDL and interferes with LDL retention to biglycan and to SEM. A
      peptide encompassing the alpha coil in the ES crystal structure mediates the
      major blocking effect of ES on LDL retention. ES inhibits the macrophage uptake
      of biglycan-associated LDL indirectly by interfering with LDL retention to
      biglycan, but it has no direct effect on the macrophage uptake of native or
      modified lipoproteins. Thus, loss of ES in advanced atheromas enhances
      lipoprotein retention in SEM. Our data reveal a third protective role of this
      vascular basement membrane component during atherosclerosis.

PMID- 15995170
TI  - Silencing of the mutant SCAP allele accounts for restoration of a normal
      phenotype in CT60 cells selected for NPC1 expression.
AB  - The sterol regulatory element binding protein (SREBP)/SREBP cleavage-activating
      protein (SCAP) complex regulates the transcription of numerous genes involved in
      cellular cholesterol metabolism. The CHO mutant, CT60, and its parental cell
      line, 25RA, possess a gain-of-function mutation in one allele of the SCAP gene
      that renders the cells resistant to sterol-mediated suppression of cholesterol
      synthesis and uptake. In addition, CT60 cells do not express a functional Niemann
      Pick type C1 (NPC1) protein, which leads to lysosomal accumulation of free
      cholesterol. Correction of the NPC1 defect by expression of a yeast artificial
      chromosome (YAC) containing the NPC1 genetic interval restored normal
      mobilization of cholesterol from the lysosomal compartment. Unexpectedly, the YAC
      containing cell lines have overall cellular cholesterol concentrations that are
      comparable to wild-type levels, despite the assumed presence of the SCAP
      mutation. This phenotypic change results from a reduction in endogenous sterol
      synthesis, LDL receptor message, and HMG-CoA reductase message. Genetic analysis
      of the SCAP gene revealed that the YAC-expressing CT60 cells have normal
      regulation of these sentinel cholesterogenic genes as a result of selective
      silencing of the mutant SCAP allele, which appears to be independent of
      functional NPC1 expression.

PMID- 15995171
TI  - Persistence of high density lipoprotein particles in obese mice lacking
      apolipoprotein A-I.
AB  - Obese mice without leptin (ob/ob) or the leptin receptor (db/db) have increased
      plasma HDL levels and accumulate a unique lipoprotein referred to as LDL/HDL1. To
      determine the role of apolipoprotein A-I (apoA-I) in the formation and
      accumulation of LDL/HDL1, both ob/ob and db/db mice were crossed onto an apoA-I
      deficient (apoA-I(-/-)) background. Even though the obese apoA-I(-/-) mice had an
      expected dramatic decrease in HDL levels, the LDL/HDL1 particle persisted. The
      cholesterol in this lipoprotein range was associated with both alpha- and beta
      migrating particles, confirming the presence of small LDLs and large HDLs.
      Moreover, in the obese apoA-I(-/-) mice, LDL particles were smaller and HDLs were
      more negatively charged and enriched in apoE compared with controls. This
      LDL/HDL1 particle was rapidly remodeled to the size of normal HDL after injection
      into C57BL/6 mice, but it was not catabolized in obese apoA-I(-/-) mice even
      though plasma hepatic lipase (HL) activity was increased significantly. The
      finding of decreased hepatic scavenger receptor class B type I (SR-BI) protein
      levels may explain the persistence of LDL/HDL1 in obese apoA-I(-/-) mice. Our
      studies suggest that the maturation and removal of large HDLs depends on the
      integrity of a functional axis of apoA-I, HL, and SR-BI. Moreover, the presence
      of large HDLs without apoA-I provides evidence for an apoA-I-independent pathway
      of cholesterol efflux, possibly sustained by apoE.

PMID- 15995172
TI  - A proteomic study of the apolipoproteins in LDL subclasses in patients with the
      metabolic syndrome and type 2 diabetes.
AB  - The exchangeable apolipoproteins present in small, dense LDL (sdLDL) and large,
      buoyant LDL subclasses were evaluated with a quantitative proteomic approach in
      patients with the metabolic syndrome and with type 2 diabetes, both with
      subclinical atherosclerosis and the B LDL phenotype. The analyses included
      surface-enhanced laser adsorption/ionization, time-of-flight mass spectrometry,
      and subsequent identification by mass spectrometry or immunoblotting and were
      carried out in LDL subclasses isolated by ultracentrifugation in deuterium oxide
      gradients with near physiological salt concentrations. The sdLDLs of both types
      of patients were enriched in apolipoprotein C-III (apoC-III) and were depleted of
      apoC-I, apoA-I, and apoE compared with matched healthy controls with the A
      phenotype. The LDL complexes formed in serum from patients with diabetes with the
      arterial proteoglycan (PG) versican were also enriched in apoC-III. In addition,
      there was a significant correlation between the apoC-III content in sdLDL in
      patients and the apparent affinity of their LDLs for arterial versican. The
      unique distribution of exchangeable apolipoproteins in the sdLDLs of the patients
      studied, especially high apoC-III, coupled with the augmented affinity with
      arterial PGs, may contribute to the strong association of the dyslipidemia of
      insulin resistance with increased risk for cardiovascular disease.

PMID- 15995173
TI  - Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex.
AB  - Previously, a microarray expression study in the yeast Saccharomyces cerevisiae
      indicated that the ERG28 gene was strongly coregulated with ergosterol
      biosynthesis. Subsequently, Erg28p was shown to function as an endoplasmic
      reticulum transmembrane protein, acting as a scaffold to tether the C-4
      demethylation enzymatic complex and also to interact with a downstream enzyme,
      Erg6p. To understand all possible protein interactions involving Erg28p in sterol
      biosynthesis, a yeast two-hybrid system designed to assess interactions between
      membrane proteins was used. The Erg28p fusion protein was used as bait to assess
      interactions with all 14 sterol biosynthetic proteins in a pairwise study based
      on two reporter systems as well as Western blots demonstrating the release of a
      transcription factor. Our results indicated that Erg28p not only interacted with
      the C-4 demethylation enzymes and Erg6p but also with Erg11p and Erg1p.
      Interactions between Erg28p and seven ergosterol biosynthetic enzymes were
      confirmed by coimmunoprecipitation experiments. Furthermore, by comparing the
      reporter gene expression levels, we demonstrate that Erg28p is most closely
      associated with Erg27p, Erg25p, Erg11p, and Erg6p and less with Erg26p and Erg1p.
      Based on these results, we suggest that many if not all sterol biosynthetic
      proteins may be tethered as a large complex.

PMID- 15995175
TI  - Sphingosine-1-phosphate inhibition of placental trophoblast differentiation
      through a G(i)-coupled receptor response.
AB  - The failure of placental trophoblasts to differentiate properly is thought to
      play an important role in the cause of pregnancy disorders such as preeclampsia.
      We looked at the effects of the bioactive lipid sphingosine-1-phosphate (S1P) on
      the differentiation of primary human cytotrophoblasts (CTs) into
      syncytiotrophoblasts (STs) in culture. We found that S1P inhibited CT
      differentiation measured by human chorionic gonadotropin (hCG) secretion and the
      expression of placental alkaline phosphatase but had no effect on their fusion
      into multinucleated syncytialized cells. G-protein-linked S1P receptors 1, 2, and
      3 were found in CTs by reverse transcriptase-polymerase chain reaction, and
      receptor 1 was found by Western blot analysis. Disruption of G(i) signaling with
      pertussis toxin reversed the inhibitory effects of S1P. S1P reduced intracellular
      cAMP, and the addition of 8-bromo-cAMP reversed S1P inhibition of hCG secretion.
      Therefore, we suggest that S1P inhibits the differentiation of CTs into STs
      through G(i)-coupled S1P receptor interaction(s), leading to the inhibition of
      adenylate cyclase and reduced production of intracellular cAMP. This is the first
      reported effect of S1P on placental trophoblast function.

PMID- 15995176
TI  - Molecular and mechanistic characterization of platelet-activating factor-like
      bioactivity produced upon LDL oxidation.
AB  - Oxidation of LDL is thought to be involved in both initiating and sustaining
      atherogenesis through the formation of proinflammatory lipids and the covalent
      modification of LDL particles. Platelet-activating factor (PAF; 1-0-alkyl-2
      acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator involved in
      inflammation. Upon oxidation of LDL, oxidized phospholipids with PAF-like
      structure are generated, and some of them may act via the PAF receptor. We
      evaluated the contribution of 1-0-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine
      (C16:0 PAF) and of other PAF analogs on the PAF-like bioactivity formed upon Cu2+
      initiated oxidation of LDL. Reverse-phase HPLC purification and electrospray
      ionization-MS analyses showed that upon oxidation of LDL with inactivated PAF
      acetylhydrolase (PAF-AH), C16:0 PAF accounted for >30% of PAF-like biological
      activity and its sn-2 butenoyl analog accounted for >50%. However, upon LDL
      oxidation in the presence of exogenous 1-0-alkyl-sn-glycero-3-phosphocholine
      (lyso-PAF) without PAF-AH inactivation, C16:0 PAF formation accounted for >90% of
      the biological activity recovered. We suggest that the C16:0 PAF, despite being a
      minor constituent of the LDL peroxidation products, may contribute substantially
      to the bioactivity formed in oxidized LDL. The higher bioactivity of C16:0 PAF,
      and the higher selectivity of the LDL-attached lyso-PAF transacetylase toward
      very short acyl chains [acetate (C2) vs. butanate (C4)], may explain the
      contribution described above.

PMID- 15995174
TI  - Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol
      induced apoptosis in macrophages.
AB  - 7-Ketocholesterol (7KC) is a cytotoxic component of oxidized low density
      lipoproteins (OxLDLs) and induces apoptosis in macrophages by a mechanism
      involving the activation of cytosolic phospholipase A2 (cPLA2). In the current
      study, we examined the role of ACAT in 7KC-induced and OxLDL-induced apoptosis in
      murine macrophages. An ACAT inhibitor, Sandoz 58-035, suppressed 7KC-induced
      apoptosis in P388D1 cells and both 7KC-induced and OxLDL-induced apoptosis in
      mouse peritoneal macrophages (MPMs). Furthermore, compared with wild-type MPMs,
      ACAT-1-deficient MPMs demonstrated significant resistance to both 7KC-induced and
      OxLDL-induced apoptosis. Macrophages treated with 7KC accumulated ACAT-derived
      [14C]cholesteryl and [3H]7-ketocholesteryl esters. Tandem LC-MS revealed that the
      7KC esters contained primarily saturated and monounsaturated fatty acids. An
      inhibitor of cPLA2, arachidonyl trifluoromethyl ketone, prevented the
      accumulation of 7KC esters and inhibited 7KC-induced apoptosis in P388D1 cells.
      The decrease in 7KC ester accumulation produced by the inhibition of cPLA2 was
      reversed by supplementing with either oleic or arachidonic acid (AA); however,
      only AA supplementation restored the induction of apoptosis by 7KC. These results
      suggest that 7KC not only initiates the apoptosis pathway by activating cPLA2, as
      we have reported previously, but also participates in the downstream signaling
      pathway when esterified by ACAT to form 7KC-arachidonate.

PMID- 15995177
TI  - Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa
      rats.
AB  - Hepatic steatosis is commonly present during the development of insulin
      resistance, and it is a clear sign of lipotoxicity attributable in part to an
      accelerated lipogenesis. There is evidence that a soy protein diet prevents the
      overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1),
      decreasing lipid accumulation. Therefore, the aim of the present work was to
      study whether a soy protein diet may prevent the development of fatty liver
      through the regulation of transcription factors involved in lipid metabolism in
      hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic
      cholesterol and triglyceride levels, as well as VLDL-triglyceride and LDL
      cholesterol, were significantly lower in rats fed soy protein than in rats fed a
      casein diet for 160 days. The reduction in hepatic cholesterol was associated
      with a low expression of liver X receptor-alpha and its target genes, 7-alpha
      hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and
      several of its target genes, FAS, stearoyl-CoA desaturase-1, and delta5 and
      delta6 desaturases, decreasing lipogenesis even in the presence of
      hyperinsulinemia. Reduction in SREBP-1 was not associated with the presence of
      soy isoflavones. Finally, soy protein reduced SREBP-1 expression in adipocytes,
      preventing hypertrophy, which also helps prevent the development of hepatic
      lipotoxicity.

PMID- 15995178
TI  - The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels
      differs with vascular disease status.
AB  - Paraoxonase (PON1) is an HDL-associated enzyme. Low PON1 activity predicts
      vascular disease status and is a more reliable predictor of vascular disease than
      are functional PON1 genotypes. There is evidence that the relationship of PON1 to
      vascular disease is, in part, due to its antioxidant activity. However, the
      physical relationship of PON1 with HDL and the existence of cholesterol pathway
      regulatory elements at the PON1 locus suggest a further relationship of PON1 with
      lipoproteins, which may contribute to its role in vascular disease. We
      investigated the relationship of PON1 activity and genotype to lipid-related
      traits in 91 Caucasian men with severe carotid artery disease and 184 without
      vascular disease who were not on lipid-lowering medications. Prior studies of
      PON1 relationship to lipids have not stratified by disease status.. We found that
      PON1 activity was correlated with HDL traits in controls and with LDL- and VLDL
      related traits in cases. We hypothesize differences in the joint regulation of
      PON1 and lipoproteins in cases and controls.

PMID- 15995179
TI  - Lipid efflux in human and mouse macrophagic cells: evidence for differential
      regulation of phospholipid and cholesterol efflux.
AB  - ABCA1 is a critical regulator of lipid efflux from cells, which is highly
      regulated at the transcriptional and posttranslational levels. However, cells
      from different species and different tissues, and primary versus immortalized
      cells, show different modes of regulation. We have carried out a comparative
      analysis of basic signaling pathways of lipid efflux in mouse J774 cells, mouse
      peritoneal macrophages (MPMs), human THP-1 cells, and human monocyte-derived
      macrophages. Cyclic AMP (cAMP) was a potent stimulator of lipid efflux in mouse
      macrophages, but not in human macrophages. Moreover, this cAMP-inducible
      component of efflux from MPMs was inhibitable by H89 [a protein kinase A (PKA)
      inhibitor], but H89 did not affect basal efflux. On the other hand, cAMP failed
      to show any stimulatory effect in human macrophages, but basal efflux was
      inhibitable by H89. In MPMs and THP-1 cells, protein kinase C (PKC) inhibitors
      blocked cholesterol efflux but had no effect on phospholipid efflux,
      demonstrating the separation of the regulation of phospholipid efflux and
      cholesterol efflux in macrophages. We conclude that: 1) cAMP regulates lipid
      efflux predominantly in a PKA-dependent fashion; 2) cholesterol efflux is
      modulated by a PKC-dependent mechanism; and 3) mouse and human macrophages
      exhibit different modes of regulation of lipid efflux.

PMID- 15995182
TI  - Determining hepatic triglyceride production in mice: comparison of poloxamer 407
      with Triton WR-1339.
AB  - Triglyceride (TG), a water-insoluble energy-rich lipid, is secreted by the liver
      as part of very low density lipoproteins (VLDLs) to supply energy to extrahepatic
      tissues. Overproduction of VLDL is associated with increased risk of
      cardiovascular heart disease; this has renewed an interest in factors that affect
      hepatic TG production. The TG production rate is determined by measuring temporal
      increases in plasma TG under conditions in which TG hydrolysis by lipoprotein
      lipase (LPL) is inhibited. The nonionic detergent, Triton WR-1339 (Triton), has
      commonly been used to inhibit LPL for this purpose. Triton, in addition to
      inhibition of TG hydrolysis, has properties that have the potential to adversely
      influence lipoprotein metabolism. Another nonionic detergent, poloxamer 407 (P
      407), also inhibits LPL. In these studies, we demonstrate that P-407 is
      comparable to Triton in the determination of TG production but without the
      unwanted side effects of Triton.

PMID- 15995183
TI  - Escherichia coli HypA is a zinc metalloprotein with a weak affinity for nickel.
AB  - The hyp operon encodes accessory proteins that are required for the maturation of
      the [NiFe] hydrogenase enzymes and, in some organisms, for the production of
      urease enzymes as well. HypA or a homologous protein is required for nickel
      insertion into the hydrogenase precursor proteins. In this study, recombinant
      HypA from Escherichia coli was purified and characterized in vitro. Metal
      analysis was used to demonstrate that HypA simultaneously binds stoichiometric
      Zn(2+) and stoichiometric Ni(2+). Competition experiments with a metallochromic
      indicator reveal that HypA binds zinc with nanomolar affinity. Spectroscopic
      analysis of cobalt-containing HypA provides evidence for a tetrathiolate
      coordination sphere, suggesting that the zinc site has a structural role. In
      addition, HypA can exist as several oligomeric complexes and the zinc content
      modulates the quaternary structure of the protein. Fluorescence titration
      experiments demonstrate that HypA binds nickel with micromolar affinity and that
      the presence of zinc does not dramatically affect the nickel-binding activity.
      Finally, complex formation between HypA and HypB, another accessory protein
      required for nickel insertion, was observed. These experiments suggest that HypA
      is an architectural component of the hydrogenase metallocenter assembly pathway
      and that it may also have a direct role in the delivery of nickel to the
      hydrogenase large subunit.

PMID- 15995184
TI  - Addition of poly(A) and heteropolymeric 3' ends in Bacillus subtilis wild-type
      and polynucleotide phosphorylase-deficient strains.
AB  - Polyadenylation plays a role in decay of some bacterial mRNAs, as well as in the
      quality control of stable RNA. In Escherichia coli, poly(A) polymerase I (PAP I)
      is the main polyadenylating enzyme, but the addition of 3' tails also occurs in
      the absence of PAP I via the synthetic activity of polynucleotide phosphorylase
      (PNPase). The nature of 3'-tail addition in Bacillus subtilis, which lacks an
      identifiable PAP I homologue, was studied. Sizing of poly(A) sequences revealed a
      similar pattern in wild-type and PNPase-deficient strains. Sequencing of 152
      cloned cDNAs, representing 3'-end sequences of nontranslated and translated RNAs,
      revealed modified ends mostly on incomplete transcripts, which are likely to be
      decay intermediates. The 3'-end additions consisted of either short poly(A)
      sequences or longer heteropolymeric ends with a mean size of about 40
      nucleotides. Interestingly, multiple independent clones exhibited complex
      heteropolymeric ends of very similar but not identical nucleotide sequences.
      Similar polyadenylated and heteropolymeric ends were observed at 3' ends of RNA
      isolated from wild-type and pnpA mutant strains. These data demonstrated that,
      unlike the case of some other bacterial species and chloroplasts, PNPase of
      Bacillus subtilis is not the major enzyme responsible for the addition of
      nucleotides to RNA 3' ends.

PMID- 15995185
TI  - The Burkholderia pseudomallei BpeAB-OprB efflux pump: expression and impact on
      quorum sensing and virulence.
AB  - BpeAB-OprB is a multidrug efflux pump of the bacterial pathogen Burkholderia
      pseudomallei and is responsible for conferring antimicrobial resistance to
      aminoglycosides and macrolides. Expression of bpeAB-oprB is inducible by its
      substrate erythromycin and upon entry into stationary phase. BpeR, a member of
      the TetR family, functions as a repressor of the bpeAB-oprB operon. bpeR
      expression was similarly induced at stationary phase but lagged behind the
      induction of bpeAB-oprB expression. The induction of bpeAB-oprB expression could
      be advanced to the early exponential phase by exogenous addition of the B.
      pseudomallei autoinducers N-octanoyl-homoserine lactone (C8HSL) and N-decanoyl
      homoserine lactone (C10HSL), suggesting that the bpeAB-oprB operon may be quorum
      regulated. On the other hand, acyl-homoserine lactone (acyl-HSL) production was
      undetectable in the bpeAB-null mutant and strains which overexpress bpeR. The
      failure of these strains to produce acyl-HSLs seemed to be at the level of
      synthesis of acyl-HSLs, as growth-phase-dependent expression of the autoinducer
      synthase BpsI was abolished in the bpeAB-null mutant. bpsI expression remained
      growth phase dependent in the bpeR mutant which had functional BpeAB-OprB. BpeAB
      OprB function is likewise necessary for optimal production of quorum-sensing
      controlled virulence factors such as siderophore and phospholipase C and for
      biofilm formation. Cell invasion and cytotoxicity towards human lung epithelial
      (A549) and human macrophage (THP-1) cells were also significantly attenuated in
      both the bpeAB mutant and bpeR-overexpressing strains, thus suggesting the
      possibility of attenuating B. pseudomallei virulence using inhibitors of the
      BpeAB-OprB efflux pump.

PMID- 15995186
TI  - The genome of Salmonella enterica serovar gallinarum: distinct
      insertions/deletions and rare rearrangements.
AB  - Salmonella enterica serovar Gallinarum is a fowl-adapted pathogen, causing
      typhoid fever in chickens. It has the same antigenic formula (1,9,12:--:--) as S.
      enterica serovar Pullorum, which is also adapted to fowl but causes pullorum
      disease (diarrhea). The close relatedness but distinct pathogeneses make this
      pair of fowl pathogens good models for studies of bacterial genomic evolution and
      the way these organisms acquired pathogenicity. To locate and characterize the
      genomic differences between serovar Gallinarum and other salmonellae, we
      constructed a physical map of serovar Gallinarum strain SARB21 by using I-CeuI,
      XbaI, and AvrII with pulsed-field gel electrophoresis techniques. In the 4,740-kb
      genome, we located two insertions and six deletions relative to the genome of S.
      enterica serovar Typhimurium LT2, which we used as a reference Salmonella genome.
      Four of the genomic regions with reduced lengths corresponded to the four
      prophages in the genome of serovar Typhimurium LT2, and the others contained
      several smaller deletions relative to serovar Typhimurium LT2, including regions
      containing srfJ, std, and stj and gene clusters encoding a type I restriction
      system in serovar Typhimurium LT2. The map also revealed some rare
      rearrangements, including two inversions and several translocations. Further
      characterization of these insertions, deletions, and rearrangements will provide
      new insights into the molecular basis for the specific host-pathogen interactions
      and mechanisms of genomic evolution to create a new pathogen.

PMID- 15995187
TI  - The IncP-6 plasmid Rms149 consists of a small mobilizable backbone with multiple
      large insertions.
AB  - Plasmid Rms149, the archetype of Pseudomonas plasmid incompatibility group IncP
      6, was identified in Pseudomonas aeruginosa as an agent conferring resistance to
      streptomycin, sulfanilamide, gentamicin, and carbenicillin in 1975. It has been
      classed as a broad-host-range plasmid due to its ability to replicate in both
      Escherichia coli (where it is designated IncG) and Pseudomonas species, although
      both species are gamma-proteobacteria. To provide reference information on this
      Inc group, we have determined the complete sequence of Rms149 and found that,
      although the genome comprises 57,121 bp, it is essentially a small mobilizable
      plasmid carrying multiple mobile elements, which make up 79% (>45 kb) of its
      genome. A replicon has been identified which encodes a single polypeptide with
      moderate identity to other replication proteins. The region encoding this protein
      can replicate in Pseudomonas putida and E. coli. This sequence is directly
      downstream of a putative partitioning region highly similar to that of pRA2. A
      functional IncQ-type mobilization region is also present. Thus, the backbone
      appears to be a novel combination of modules already identified in other plasmid
      systems. Analysis of the segments that fall outside this core of stable
      inheritance and transfer functions show that this plasmid has been subject to
      multiple insertion events and that the plasmid appears to carry a considerable
      load of DNA that no longer should be phenotypically advantageous. The plasmid
      therefore functions not just as a vehicle for spread of selective traits but also
      as a store for DNA that is not currently under selection.

PMID- 15995188
TI  - Analysis of the Escherichia coli Alp phenotype: heat shock induction in ssrA
      mutants.
AB  - The major phenotypes of lon mutations, UV sensitivity and overproduction of
      capsule, are due to the stabilization of two substrates, SulA and RcsA.
      Inactivation of transfer mRNA (tmRNA) (encoded by ssrA), coupled with a multicopy
      kanamycin resistance determinant, suppressed both lon phenotypes and restored the
      rapid degradation of SulA. This novel protease activity was named Alp but was
      never identified further. We report here the identification, mapping, and
      characterization of a chromosomal mutation, faa (for function affecting Alp),
      that leads to full suppression of a Deltalon ssrA::cat host and thus bypasses the
      requirement for multicopy Kan(r); faa and ssrA mutants are additive in their
      ability to suppress lon mutants. The faa mutation was mapped to the C terminus of
      dnaJ(G232); dnaJ null mutants have similar effects. The identification of a lon
      suppressor in dnaJ suggested the possible involvement of heat shock. We find that
      ssrA mutants alone significantly induce the heat shock response. The suppression
      of UV sensitivity, both in the original Alp strain and in faa mutants, is
      reversed by mutations in clpY, encoding a subunit of the heat shock-induced ClpYQ
      protease that is known to degrade SulA. However, capsule synthesis is not
      restored by clpY mutants, probably because less RcsA accumulates in the Alp
      strain and because the RcsA that does accumulate is inactive. Both ssrA effects
      are partially relieved by ssrA derivatives encoding protease-resistant tags,
      implicating ribosome stalling as the primary defect. Thus, ssrA and faa each
      suppress two lon mutant phenotypes but by somewhat different mechanisms, with
      heat shock induction playing a major role.

PMID- 15995189
TI  - Chill activation of compatible solute transporters in Corynebacterium glutamicum
      at the level of transport activity.
AB  - The gram-positive soil bacterium Corynebacterium glutamicum harbors four
      osmoregulated secondary uptake systems for compatible solutes, BetP, EctP, LcoP,
      and ProP. When reconstituted in proteoliposomes, BetP was shown to sense
      hyperosmotic conditions via the increase in luminal K(+) and to respond by
      instant activation. To study further putative ways of stimulus perception and
      signal transduction, we have investigated the responses of EctP, LcoP, and BetP,
      all belonging to the betaine-carnitine-choline transporter family, to chill
      stress at the level of activity. When fully activated by hyperosmotic stress,
      they showed the expected increase of activity at increasing temperature. In the
      absence of osmotic stress, EctP was not activated by chill and LcoP to only a
      very low extent, whereas BetP was significantly stimulated at low temperature.
      BetP was maximally activated at 10 degrees C, reaching the same transport rate as
      that observed under hyperosmotic conditions at this temperature. A role of
      cytoplasmic K(+) in chill-dependent activation of BetP was ruled out, since (i)
      the cytoplasmic K(+) concentration did not change significantly at lower
      temperatures and (ii) a mutant BetP lacking the C-terminal 25 amino acids, which
      was previously shown to have lost the ability to be activated by luminal K(+),
      was fully competent in chill sensing. When heterologously expressed in
      Escherichia coli, BetP did not respond to chill stress. This may indicate that
      the membrane in which BetP is inserted plays an important role in chill
      activation and thus in signal transduction by BetP, different from the previously
      established K(+)-mediated process.

PMID- 15995190
TI  - Identification of phthiodiolone ketoreductase, an enzyme required for production
      of mycobacterial diacyl phthiocerol virulence factors.
AB  - Diacyl phthiocerol esters and their congeners are mycobacterial virulence
      factors. The biosynthesis of these complex lipids remains poorly understood.
      Insight into their biosynthesis will aid the development of rationally designed
      drugs that inhibit their production. In this study, we investigate a biosynthetic
      step required for diacyl (phenol)phthiocerol ester production, i.e., the
      reduction of the keto group of (phenol)phthiodiolones. We utilized comparative
      genomics to identify phthiodiolone ketoreductase gene candidates and provide a
      genetic analysis demonstrating gene function for two of these candidates.
      Moreover, we present data confirming the existence of a diacyl phthiotriol
      intermediate in diacyl phthiocerol biosynthesis. We also elucidate the mechanism
      underlying diacyl phthiocerol deficiency in some mycobacteria, such as
      Mycobacterium ulcerans and Mycobacterium kansasii. Overall, our findings shed
      additional light on the biosynthesis of an important group of mycobacterial
      lipids involved in virulence.

PMID- 15995192
TI  - The ubiquitous protein domain EAL is a cyclic diguanylate-specific
      phosphodiesterase: enzymatically active and inactive EAL domains.
AB  - The EAL domain (also known as domain of unknown function 2 or DUF2) is a
      ubiquitous signal transduction protein domain in the Bacteria. Its involvement in
      hydrolysis of the novel second messenger cyclic dimeric GMP (c-di-GMP) was
      demonstrated in vivo but not in vitro. The EAL domain-containing protein Dos from
      Escherichia coli was reported to hydrolyze cyclic AMP (cAMP), implying that EAL
      domains have different substrate specificities. To investigate the biochemical
      activity of EAL, the E. coli EAL domain-containing protein YahA and its
      individual EAL domain were overexpressed, purified, and characterized in vitro.
      Both full-length YahA and the EAL domain hydrolyzed c-di-GMP into linear dimeric
      GMP, providing the first biochemical evidence that the EAL domain is sufficient
      for phosphodiesterase activity. This activity was c-di-GMP specific, optimal at
      alkaline pH, dependent on Mg(2+) or Mn(2+), strongly inhibited by Ca(2+), and
      independent of protein oligomerization. Linear dimeric GMP was shown to be
      5'pGpG. The EAL domain from Dos was overexpressed, purified, and found to
      function as a c-di-GMP-specific phosphodiesterase, not as a cAMP-specific
      phosphodiesterase, in contrast to previous reports. The EAL domains can hydrolyze
      5'pGpG into GMP, however, very slowly, thus implying that this activity is
      irrelevant in vivo. Therefore, c-di-GMP is the exclusive substrate of EAL.
      Multiple-sequence alignment revealed two groups of EAL domains hypothesized to
      correspond to enzymatically active and inactive domains. The domains in the
      latter group have mutations in residues conserved in the active domains. The
      enzymatic inactivity of EAL domains may explain their coexistence with GGDEF
      domains in proteins possessing c-di-GMP synthase (diguanulate cyclase) activity.

PMID- 15995191
TI  - Mutations in the C-terminal region of TraM provide evidence for in vivo TraM-TraD
      interactions during F-plasmid conjugation.
AB  - Conjugation is a major mechanism for disseminating genetic information in
      bacterial populations, but the signal that triggers it is poorly understood in
      gram-negative bacteria. F-plasmid-mediated conjugation requires TraM, a
      homotetramer, which binds cooperatively to three binding sites within the origin
      of transfer. Using in vitro assays, TraM has previously been shown to interact
      with the coupling protein TraD. Here we present evidence that F conjugation also
      requires TraM-TraD interactions in vivo. A three-plasmid system was used to
      select mutations in TraM that are defective for F conjugation but competent for
      tetramerization and cooperative DNA binding to the traM promoter region. One
      mutation, K99E, was particularly defective in conjugation and was further
      characterized by affinity chromatography and coimmunoprecipitation assays that
      suggested it was defective in interacting with TraD. A C-terminal deletion (S79*,
      where the asterisk represents a stop codon) and a missense mutation (F121S),
      which affects tetramerization, also reduced the affinity of TraM for TraD. We
      propose that the C-terminal region of TraM interacts with TraD, whereas its N
      terminal domain is involved in DNA binding. This arrangement of functional
      domains could in part allow TraM to receive the mating signal generated by donor
      recipient contact and transfer it to the relaxosome, thereby triggering DNA
      transfer.

PMID- 15995193
TI  - Transcription analysis of the major antigenic protein 1 multigene family of three
      in vitro-cultured Ehrlichia ruminantium isolates.
AB  - Ehrlichia ruminantium, an obligate intracellular bacterium transmitted by ticks
      of the genus Amblyomma, causes heartwater disease in ruminants. The gene coding
      for the major antigenic protein MAP1 is part of a multigene family consisting of
      a cluster containing 16 paralogs. In the search for differentially regulated
      genes between E. ruminantium grown in endothelial and tick cell lines that could
      be used in vaccine development and to determine if differences in the map1 gene
      cluster exist between different isolates of E. ruminantium, we analyzed the map1
      gene cluster of the Senegal and Gardel isolates of E. ruminantium. Both isolates
      contained the same number of genes, and the same organization as found in the
      genome sequence of the Welgevonden isolate (H. Van Heerden, N. E. Collins, K. A.
      Brayton, C. Rademeyer, and B. A. Allsopp, Gene 330:159-168, 2004). However,
      comparison of two subpopulations of the Gardel isolate maintained in different
      laboratories demonstrated that recombination between map1-3 and map1-2 had
      occurred in one subpopulation with deletion of one entire gene. Reverse
      transcription-PCR on E. ruminantium derived mRNA from infected cells using gene
      specific primers revealed that all 16 map1 paralogs were transcribed in
      endothelial cells. In one vector (Amblyomma variegatum) and several nonvector
      tick cell lines infected with E. ruminantium, transcripts were found for between
      4 and 11 paralogs. In all these cases the transcript for the map1-1 gene was
      detected and was predominant. Our results indicate that the map1 gene cluster is
      relatively conserved but can be subject to recombination, and differences in the
      transcription of map1 multigenes in host and vector cell environments exist.

PMID- 15995194
TI  - ExpR, a LuxR homolog of Erwinia carotovora subsp. carotovora, activates
      transcription of rsmA, which specifies a global regulatory RNA-binding protein.
AB  - N-acyl homoserine lactone (AHL) is required by Erwinia carotovora subspecies for
      the expression of various traits, including extracellular enzyme and protein
      production and pathogenicity. Previous studies with E. carotovora subsp.
      carotovora have shown that AHL deficiency causes the production of high levels of
      RsmA, an RNA binding protein that functions as a global negative regulator of
      extracellular enzymes and proteins and secondary metabolites (Rsm, regulator of
      secondary metabolites). We document here that ExpR, a putative AHL receptor
      belonging to the LuxR family of regulators, activates RsmA production. In the
      absence of AHL, an ExpR(+) E. carotovora subsp. carotovora strain compared to its
      ExpR(-) mutant, produces higher levels of rsmA RNA and better expresses an rsmA
      lacZ transcriptional fusion. Moreover, the expression of the rsmA-lacZ fusion in
      Escherichia coli is much higher in the presence of expR(71) (the expR gene of E.
      carotovora subsp. carotovora strain Ecc71) than in its absence. We also show that
      purified preparation of MBP-ExpR(71) binds (MBP, maltose binding protein) rsmA
      DNA. By contrast, MBP-ExpR(71) does not bind ahlI (gene for AHL synthase), pel-1
      (gene for pectate lyase), or rsmB (gene for regulatory RNA that binds RsmA), nor
      does ExpR(71) activate expression of these genes. These observations strongly
      suggest transcriptional activation of rsmA resulting from a direct and specific
      interaction between ExpR(71) and the rsmA promoter. Several lines of evidence
      establish that N-3-oxohexanoyl-L-homoserine lactone (3-oxo-C6-HL), the major AHL
      analog produced by E. carotovora subsp. carotovora strain Ecc71, inhibits
      ExpR(71)-mediated activation of rsmA expression. These findings for the first
      time establish that the expR effect in E. carotovora subsp. carotovora is
      channeled via RsmA, a posttranscriptional regulator of E. carotovora subspecies,
      and AHL neutralizes this ExpR effect.

PMID- 15995195
TI  - Mutational analysis of 16S and 23S rRNA genes of Thermus thermophilus.
AB  - Structural studies of the ribosome have benefited greatly from the use of
      organisms adapted to extreme environments. However, little is known about the
      mechanisms by which ribosomes or other ribonucleoprotein complexes have adapted
      to functioning under extreme conditions, and it is unclear to what degree mutant
      phenotypes of extremophiles will resemble those of their counterparts adapted to
      more moderate environments. It is conceivable that phenotypes of mutations
      affecting thermophilic ribosomes, for instance, will be influenced by structural
      adaptations specific to a thermophilic existence. This consideration is
      particularly important when using crystal structures of thermophilic ribosomes to
      interpret genetic results from nonextremophilic species. To address this issue,
      we have conducted a survey of spontaneously arising antibiotic-resistant mutants
      of the extremely thermophilic bacterium Thermus thermophilus, a species which has
      featured prominently in ribosome structural studies. We have accumulated over 20
      single-base substitutions in T. thermophilus 16S and 23S rRNA, in the decoding
      site and in the peptidyltransferase active site of the ribosome. These mutations
      produce phenotypes that are largely identical to those of corresponding mutants
      of mesophilic organisms encompassing a broad phylogenetic range, suggesting that
      T. thermophilus may be an ideal model system for the study of ribosome structure
      and function.

PMID- 15995196
TI  - Enhancement of glutamine utilization in Bacillus subtilis through the GlnK-GlnL
      two-component regulatory system.
AB  - During DNA microarray analysis, we discovered that the GlnK-GlnL (formerly YcbA
      YcbB) two-component system positively regulates the expression of the glsA-glnT
      (formerly ybgJ-ybgH) operon in response to glutamine in the culture medium on
      Northern analysis. As a result of gel retardation and DNase I footprinting
      analyses, we found that the GlnL protein interacts with a region (bases -13 to 
      56; +1 is the transcription initiation base determined on primer extension
      analysis of glsA-glnT) in which a direct repeat, TTTTGTN4TTTTGT, is present.
      Furthermore, the glsA and glnT genes were biochemically verified to encode
      glutaminase and glutamine transporter, respectively.

PMID- 15995197
TI  - Analysis of the ospC regulatory element controlled by the RpoN-RpoS regulatory
      pathway in Borrelia burgdorferi.
AB  - Outer surface lipoprotein C (OspC) is a key virulence factor of Borrelia
      burgdorferi. ospC is differentially regulated during borrelial transmission from
      ticks to rodents, and such regulation is essential for maintaining the spirochete
      in its natural enzootic cycle. Recently, we showed that the expression of ospC in
      B. burgdorferi is governed by a novel alternative sigma factor regulatory
      network, the RpoN-RpoS pathway. However, the precise mechanism by which the RpoN
      RpoS pathway controls ospC expression has been unclear. In particular, there has
      been uncertainty regarding whether ospC is controlled directly by RpoS (sigma(s))
      or indirectly through a transactivator (induced by RpoS). Using deletion analyses
      and genetic complementation in an OspC-deficient mutant of B. burgdorferi, we
      analyzed the cis element(s) required for the expression of ospC in its native
      borrelial background. Two highly conserved upstream inverted repeat elements,
      previously implicated in ospC regulation, were not required for ospC expression
      in B. burgdorferi. Using similar approaches, a minimal promoter that contained a
      canonical -35/-10 sequence necessary and sufficient for sigma(s)-dependent
      regulation of ospC was identified. Further, targeted mutagenesis of a C at
      position -15 within the extended -10 region of ospC, which is postulated to
      function like the strategic C residue important for Esigma(s) binding in
      Escherichia coli, abolished ospC expression. The minimal ospC promoter also was
      responsive to coumermycin A(1), further supporting its sigma(s) character. The
      combined data constitute a body of evidence that the RpoN-RpoS regulatory network
      controls ospC expression by direct binding of sigma(s) to a sigma(s)-dependent
      promoter of ospC. The implication of our findings to understanding how B.
      burgdorferi differentially regulates ospC and other ospC-like genes via the RpoN
      RpoS regulatory pathway is discussed.

PMID- 15995198
TI  - Specific control of endogenous cCF10 pheromone by a conserved domain of the pCF10
      encoded regulatory protein PrgY in Enterococcus faecalis.
AB  - Conjugative transfer of Enterococcus faecalis plasmid pCF10 is induced by the
      heptapeptide pheromone cCF10. cCF10 produced by plasmid-free recipient cells is
      detected by pCF10-containing donor cells, which respond by induction of plasmid
      encoded transfer functions. The pCF10-encoded membrane protein PrgY is essential
      to prevent donor cells from responding to endogenously produced pheromone while
      maintaining the ability to respond to pheromone from an exogenous source; this
      function has not been identified in any nonenterococcal prokaryotic signaling
      system. PrgY specifically inhibited endogenous cCF10 and cPD1 (a pheromone that
      induces transfer of closely related plasmid pPD1) but not cAD1 (which is specific
      for less-related plasmid pAD1). Ectopic expression of PrgY in plasmid-free
      recipient cells reduced pheromone activity in culture supernatants and reduced
      the ability of these cells to acquire pCF10 by conjugation but did not have any
      effect on the interaction of these cells with exogenously supplied cCF10. The
      cloned prgY gene could complement a pCF10 prgY null mutation, and complementation
      was used to identify point mutations impairing PrgY function. Such mutations also
      abolished the inhibitory effect of PrgY expression in recipients on pheromone
      production and on acquisition of pCF10. Most randomly generated point mutations
      identified in the genetic screen mapped to a predicted extracellular domain in
      the N terminus of PrgY that is conserved in a newly identified family of related
      proteins from disparate species including Borrelia burgdorferi, Archaeoglobus
      fulgidus, Arabidopsis thaliana, and Homo sapiens. The combined genetic and
      physiological data suggest that PrgY may sequester or inactivate cCF10 as it is
      released from the membrane.

PMID- 15995199
TI  - Citrate synthase mutants of Agrobacterium are attenuated in virulence and display
      reduced vir gene induction.
AB  - A citrate synthase (CS) deletion mutant of Agrobacterium tumefaciens C58 is
      highly attenuated in virulence. The identity of the mutant was initially
      determined from its amino acid sequence, which is 68% identical to Escherichia
      coli and 77% identical to Brucella melitensis. The mutant lost all CS enzymatic
      activity, and a cloned CS gene complemented a CS mutation in Sinorhizobium. The
      CS mutation resulted in a 10-fold reduction in vir gene expression, which likely
      accounts for the attenuated virulence. When a plasmid containing a constitutive
      virG [virG(Con)] locus was introduced into this mutant, the level of vir gene
      induction was restored to nearly wild-type level. Further, the virG(Con)
      complemented CS mutant strain induced tumors that were similar in size and number
      to those induced by the parental strain. The CS mutation resulted in only a minor
      reduction in growth rate in a glucose-salts medium. Both the CS mutant and the
      virG(Con)-complemented CS strain displayed similar growth deficiencies in a
      glucose-salts medium, indicating that the reduced growth rate of the CS mutant
      could not be responsible for the attenuated virulence. A search of the genome of
      A. tumefaciens C58 revealed four proteins, encoded on different replicons, with
      conserved CS motifs. However, only the locus that when mutated resulted in an
      attenuated phenotype has CS activity. Mutations in the other three loci did not
      result in attenuated virulence and any loss of CS activity, and none were able to
      complement the CS mutation in Sinorhizobium. The function of these loci remains
      unknown.

PMID- 15995200
TI  - Global analysis of cellular factors and responses involved in Pseudomonas
      aeruginosa resistance to arsenite.
AB  - The impact of arsenite [As(III)] on several levels of cellular metabolism and
      gene regulation was examined in Pseudomonas aeruginosa. P. aeruginosa isogenic
      mutants devoid of antioxidant enzymes or defective in various metabolic pathways,
      DNA repair systems, metal storage proteins, global regulators, or quorum sensing
      circuitry were examined for their sensitivity to As(III). Mutants lacking the
      As(III) translocator (ArsB), superoxide dismutase (SOD), catabolite repression
      control protein (Crc), or glutathione reductase (Gor) were more sensitive to
      As(III) than wild-type bacteria. The MICs of As(III) under aerobic conditions
      were 0.2, 0.3, 0.8, and 1.9 mM for arsB, sodA sodB, crc, and gor mutants,
      respectively, and were 1.5- to 13-fold less than the MIC for the wild-type
      strain. A two-dimensional gel/matrix-assisted laser desorption ionization-time of
      flight analysis of As(III)-treated wild-type bacteria showed significantly (>40
      fold) increased levels of a heat shock protein (IbpA) and a putative allo
      threonine aldolase (GlyI). Smaller increases (up to 3.1-fold) in expression were
      observed for acetyl-coenzyme A acetyltransferase (AtoB), a probable aldehyde
      dehydrogenase (KauB), ribosomal protein L25 (RplY), and the probable DNA-binding
      stress protein (PA0962). In contrast, decreased levels of a heme oxygenase
      (HemO/PigA) were found upon As(III) treatment. Isogenic mutants were successfully
      constructed for six of the eight genes encoding the aforementioned proteins. When
      treated with sublethal concentrations of As(III), each mutant revealed a marginal
      to significant lag period prior to resumption of apparent normal growth compared
      to that observed in the wild-type strain. Our results suggest that As(III)
      exposure results in an oxidative stress-like response in P. aeruginosa, although
      activities of classic oxidative stress enzymes are not increased. Instead, relief
      from As(III)-based oxidative stress is accomplished from the collective
      activities of ArsB, glutathione reductase, and the global regulator Crc. SOD
      appears to be involved, but its function may be in the protection of superoxide
      sensitive sulfhydryl groups.

PMID- 15995201
TI  - Identification of the iron-responsive genes of Neisseria gonorrhoeae by
      microarray analysis in defined medium.
AB  - To ensure survival, most bacteria must acquire iron, a resource that is
      sequestered by mammalian hosts. Pathogenic bacteria have therefore evolved
      intricate systems to sense iron limitation and regulate gene expression
      appropriately. We used a pan-Neisseria microarray to examine genes regulated in
      Neisseria gonorrhoeae in response to iron availability in defined medium.
      Overall, 203 genes varied in expression, 109 up-regulated and 94 down-regulated
      by iron deprivation. In iron-replete medium, genes essential to rapid bacterial
      growth were preferentially expressed, while iron transport functions, and
      predominantly genes of unknown function, were expressed in low-iron medium. Of
      those TonB-dependent proteins encoded in the FA1090 genome with unknown ligand
      specificity, expression of three was not controlled by iron availability,
      suggesting that these receptors may not be high-affinity transporters for iron
      containing ligands. Approximately 30% of the operons regulated by iron appeared
      to be directly under control of Fur. Our data suggest a regulatory cascade where
      Fur indirectly controls gene expression by affecting the transcription of three
      secondary regulators. Our data also suggest that a second MerR-like regulator may
      be directly responding to iron availability and controlling transcription
      independent of the Fur protein. Comparison of our data with those recently
      published for Neisseria meningitidis revealed that only a small portion of genes
      were found to be similarly regulated in these closely related pathogens, while a
      large number of genes derepressed during iron starvation were unique to each
      organism.

PMID- 15995202
TI  - Quorum-sensing-negative (lasR) mutants of Pseudomonas aeruginosa avoid cell lysis
      and death.
AB  - In Pseudomonas aeruginosa, N-acylhomoserine lactone signals regulate the
      expression of several hundreds of genes, via the transcriptional regulator LasR
      and, in part, also via the subordinate regulator RhlR. This regulatory network
      termed quorum sensing contributes to the virulence of P. aeruginosa as a
      pathogen. The fact that two supposed PAO1 wild-type strains from strain
      collections were found to be defective for LasR function because of independent
      point mutations in the lasR gene led to the hypothesis that loss of quorum
      sensing might confer a selective advantage on P. aeruginosa under certain
      environmental conditions. A convenient plate assay for LasR function was devised,
      based on the observation that lasR mutants did not grow on adenosine as the sole
      carbon source because a key degradative enzyme, nucleoside hydrolase (Nuh), is
      positively controlled by LasR. The wild-type PAO1 and lasR mutants showed similar
      growth rates when incubated in nutrient yeast broth at pH 6.8 and 37 degrees C
      with good aeration. However, after termination of growth during 30 to 54 h of
      incubation, when the pH rose to > or = 9, the lasR mutants were significantly
      more resistant to cell lysis and death than was the wild type. As a consequence,
      the lasR mutant-to-wild-type ratio increased about 10-fold in mixed cultures
      incubated for 54 h. In a PAO1 culture, five consecutive cycles of 48 h of
      incubation sufficed to enrich for about 10% of spontaneous mutants with a Nuh(-)
      phenotype, and five of these mutants, which were functionally complemented by
      lasR(+), had mutations in lasR. The observation that, in buffered nutrient yeast
      broth, the wild type and lasR mutants exhibited similar low tendencies to undergo
      cell lysis and death suggests that alkaline stress may be a critical factor
      providing a selective survival advantage to lasR mutants.

PMID- 15995203
TI  - Molecular cloning and transcriptional and expression analysis of engO, encoding a
      new noncellulosomal family 9 enzyme, from Clostridium cellulovorans.
AB  - Clostridium cellulovorans produces a major noncellulosomal family 9 endoglucanase
      EngO. A genomic DNA fragment (40 kb) containing engO and neighboring genes was
      cloned. The nucleotide sequence contained reading frames for endoglucanase EngO,
      a putative response regulator, and a putative sensor histidine kinase protein.
      The engO gene consists of 2,172 bp and encodes a protein of 724 amino acids with
      a molecular weight of 79,474. Northern hybridizations revealed that the engO gene
      is transcribed as a monocistronic 2.6-kb mRNA. 5' RNA ligase-mediated rapid
      amplification of cDNA ends (RLM-RACE) PCR analysis indicated that the single
      transcriptional start site of engO was located 264 bp upstream from the first
      nucleotide of the translation initiation codon. Alignment of the engO promoter
      region provided evidence for highly conserved sequences that exhibited strong
      similarity to the sigma(A) consensus promoter sequences of gram-positive
      bacteria. EngO contains a typical N-terminal signal peptide of 28 amino acid
      residues, followed by a 149-amino-acid sequence which is homologous to the family
      4-9 carbohydrate-binding domain. Downstream of this domain was an immunoglobulin
      like domain of 89 amino acids. The C terminus contains a family 9 catalytic
      domain of glycosyl hydrolase. Mass spectrometry analysis of EngO was in agreement
      with that deduced from the nucleotide sequence. Expression of engO mRNA increased
      from early to middle exponential phase and decreased during the early stationary
      phase. EngO was highly active toward carboxymethyl cellulose but showed no
      activity towards xylan. It was optimally active at 40 to 50 degrees C and pH 5 to
      6. The analysis of the products from the cellulose hydrolysis through thin-layer
      chromatography indicated its endoglucanase activity.

PMID- 15995205
TI  - Rapid detection of colicin E9-induced DNA damage using Escherichia coli cells
      carrying SOS promoter-lux fusions.
AB  - ColE9 is a plasmid-encoded protein antibiotic produced by Escherichia coli and
      closely related species that kills E. coli cells expressing the BtuB receptor.
      The 15-kDa cytotoxic DNase domain of colicin E9 preferentially nicks double
      stranded DNA at thymine bases and shares a common active-site structural motif
      with a variety of other nucleases, including the H-N-H homing endonucleases and
      the apoptotic CAD proteins of eukaryotes. Studies of the mechanism by which the
      DNase domain of ColE9 reaches the cytoplasm of E. coli cells are limited by the
      lack of a rapid, sensitive assay for the DNA damage that results. Here, we report
      the development of an SOS promoter-lux fusion reporter system for monitoring DNA
      damage in colicin-treated cells and illustrate the value of this reporter system
      in experiments that probe the mechanism and time required for the DNase domain of
      colicin E9 to reach the cytoplasm.

PMID- 15995204
TI  - Hierarchical control of anaerobic gene expression in Escherichia coli K-12: the
      nitrate-responsive NarX-NarL regulatory system represses synthesis of the
      fumarate-responsive DcuS-DcuR regulatory system.
AB  - Hierarchical control ensures that facultative bacteria preferentially use the
      available respiratory electron acceptor with the most positive standard redox
      potential. Thus, nitrate is used before other electron acceptors such as fumarate
      for anaerobic respiration. Nitrate regulation is mediated by the NarX-NarL two
      component system, which activates the transcription of operons encoding nitrate
      respiration enzymes and represses the transcription of operons for other
      anaerobic respiratory enzymes, including enzymes involved in fumarate
      respiration. These are fumarate reductase (encoded by the frdABCD operon),
      fumarase B, which generates fumarate from malate, and the DcuB permease for
      fumarate, malate, and aspartate. The transcription of the corresponding
      structural genes is activated by the DcuS-DcuR two-component system in response
      to fumarate or its dicarboxylate precursors. We report results from preliminary
      transcription microarray experiments that revealed two previously unknown members
      of the NarL regulon: the aspA gene encoding aspartate-ammonia lyase, which
      generates fumarate; and the dcuSR operon encoding the dicarboxylate-responsive
      regulatory system. We measured beta-galactosidase expression from monocopy aspA
      lacZ, frdA-lacZ, and dcuS-lacZ operon fusions in response to added nitrate and
      fumarate and with respect to the dcuR and narL genotypes. Nitrate, acting through
      the NarX-NarL regulatory system, repressed the transcription of all three
      operons. Only frdA-lacZ expression, however, was responsive to added fumarate or
      a dcuR(+) genotype. Phospho-NarL protein protected operator sites in the aspA and
      dcuS promoter regions from DNase I cleavage in vitro. The overall results are
      consistent with the hypothesis that nitrate represses frdA operon transcription
      not only directly, by repressing frdA promoter activity, but also indirectly, by
      repressing dcuS promoter activity.

PMID- 15995206
TI  - A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced
      virulence and antimicrobial resistance.
AB  - The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa is a transmissible
      aggressive pathogen of cystic fibrosis (CF) patients. We compared transcriptome
      profiles of two LES isolates with each other and with a laboratory and genetic
      reference strain (PAO1) after growth to late exponential phase and following
      exposure to oxidative stress. Both LES isolates exhibited enhanced antimicrobial
      resistances linked to specific mutations in efflux pump genes. Although
      transcription of AmpC beta-lactamase was up-regulated in both, one LES isolate
      contained a specific mutation rendering the ampC gene untranslatable. The
      virulence-related quorum-sensing (QS) regulon of LES431, an isolate that caused
      pneumonia in the non-CF parent of a CF patient, was considerably up-regulated in
      comparison to either isolate LES400, associated with a chronic CF infection, or
      strain PAO1. Premature activation of QS genes was detected in isolates from both
      non-CF parents and the CF patient in a previously reported infection episode. LES
      isolates lacking the up-regulated QS phenotype contained different frameshift
      mutations in lasR. When fed to Drosophila melanogaster, isolate LES431 killed the
      fruit flies more readily than either isolate LES400 or strain PAO1, indicating
      that virulence varies intraclonally. The LES may represent a clone with enhanced
      virulence and antimicrobial resistance characteristics that can vary or are lost
      due to mutations during long-term colonization but have contributed to the
      successful spread of the lineage throughout the CF population of the United
      Kingdom.

PMID- 15995208
TI  - Genome-wide detection and analysis of cell wall-bound proteins with LPxTG-like
      sorting motifs.
AB  - Surface proteins of gram-positive bacteria often play a role in adherence of the
      bacteria to host tissue and are frequently required for virulence. A specific
      subgroup of extracellular proteins contains the cell wall-sorting motif LPxTG,
      which is the target for cleavage and covalent coupling to the peptidoglycan by
      enzymes called sortases. A comprehensive set of putative sortase substrates was
      identified by in silico analysis of 199 completely sequenced prokaryote genomes.
      A combination of detection methods was used, including secondary structure
      prediction, pattern recognition, sequence homology, and genome context
      information. With the hframe algorithm, putative substrates were identified that
      could not be detected by other methods due to errors in open reading frame
      calling, frameshifts, or sequencing errors. In total, 732 putative sortase
      substrates encoded in 49 prokaryote genomes were identified. We found striking
      species-specific variation for the LPxTG motif. A hidden Markov model (HMM) based
      on putative sortase substrates was created, which was subsequently used for the
      automatic detection of sortase substrates in recently completed genomes. A
      database was constructed, LPxTG-DB
      (http://bamics3.cmbi.kun.nl/sortase_substrates), containing for each genome a
      list of putative sortase substrates, sequence information of these substrates,
      the organism-specific HMMs based on the consensus sequence of the sortase
      recognition motif, and a graphic representation of this consensus.

PMID- 15995207
TI  - An atypical KdpD homologue from the cyanobacterium Anabaena sp. strain L-31:
      cloning, in vivo expression, and interaction with Escherichia coli KdpD-CTD.
AB  - The kdpFABC operon of Escherichia coli, coding for the high-affinity K(+)
      transport system KdpFABC, is transcriptionally regulated by the products of the
      adjacently located kdpDE genes. The KdpD protein is a membrane-bound sensor
      kinase consisting of a large N-terminal domain and a C-terminal transmitter
      domain interconnected by four transmembrane segments (the transmembrane segments
      together with the C-terminal transmitter domain of KdpD are referred to as CTD),
      while KdpE is a cytosolic response regulator. We have cloned and sequenced the
      kdp operon from a nitrogen-fixing, filamentous cyanobacterium, Anabaena sp.
      strain L-31 (GenBank accession. number AF213466). The kdpABC genes are similar in
      size to those of E. coli, but the kdpD gene is short (coding only for 365 amino
      acids), showing homology only to the N-terminal domain of E. coli KdpD. A kdpE
      like gene is absent in the vicinity of this operon. Anabaena KdpD with six C
      terminal histidines was overproduced in E. coli and purified by Ni(2+)
      nitrilotriacetic acid affinity chromatography. With antisera raised against the
      purified Anabaena KdpD, the protein was detected in Anabaena sp. strain L-31
      membranes. The membrane-associated or soluble form of the Anabaena KdpD(6His)
      could be photoaffinity labeled with the ATP analog 8-azido-ATP, indicating the
      presence of an ATP binding site. The coproduction of Anabaena KdpD with E. coli
      KdpD-CTD decreased E. coli kdpFABC expression in response to K(+) limitation in
      vivo relative to the wild-type KdpD-CTD protein. In vitro experiments revealed
      that the kinase activity of the E. coli KdpD-CTD was unaffected, but its
      phosphatase activity increased in the presence of Anabaena KdpD(6His). To our
      knowledge this is the first report where a heterologous N-terminal domain
      (Anabaena KdpD) is shown to affect in trans KdpD-CTD (E. coli) activity, which is
      just opposite to that observed for the KdpD-N-terminal domain of E. coli.

PMID- 15995209
TI  - Gene transfer and genome plasticity in Thermotoga maritima, a model
      hyperthermophilic species.
AB  - The genome sequence of the hyperthermophilic bacterium Thermotoga maritima MSB8
      presents evidence for lateral gene transfer events between bacterial and archaeal
      species. To estimate the extent of genomic diversity across the order
      Thermotogales, a comparative genomic hybridization study was initiated to compare
      nine Thermotoga strains to the sequenced T. maritima MSB8. Many differences could
      be associated with substrate utilization patterns, which are most likely a
      reflection of the environmental niche that these individual species occupy. A
      detailed analysis of some of the predicted variable regions demonstrates many
      examples of the deletion/insertion of complete cassettes of genes and of gene
      rearrangements and insertions of DNA within genes, with the C or N terminus being
      retained. Although the mechanism for gene transfer in this lineage remains to be
      elucidated, this analysis suggests possible associations with repetitive elements
      and highlights the possible benefits of rampant genetic exchange to these
      species.

PMID- 15995211
TI  - Crystal structure of an iron-dependent group III dehydrogenase that interconverts
      L-lactaldehyde and L-1,2-propanediol in Escherichia coli.
AB  - The FucO protein, a member of the group III "iron-activated" dehydrogenases,
      catalyzes the interconversion between L-lactaldehyde and L-1,2-propanediol in
      Escherichia coli. The three-dimensional structure of FucO in a complex with
      NAD(+) was solved, and the presence of iron in the crystals was confirmed by X
      ray fluorescence. The FucO structure presented here is the first structure for a
      member of the group III bacterial dehydrogenases shown experimentally to contain
      iron. FucO forms a dimer, in which each monomer folds into an alpha/beta
      dinucleotide-binding N-terminal domain and an all-alpha-helix C-terminal domain
      that are separated by a deep cleft. The dimer is formed by the swapping (between
      monomers) of the first chain of the beta-sheet. The binding site for Fe(2+) is
      located at the face of the cleft formed by the C-terminal domain, where the metal
      ion is tetrahedrally coordinated by three histidine residues (His200, His263, and
      His277) and an aspartate residue (Asp196). The glycine-rich turn formed by
      residues 96 to 98 and the following alpha-helix is part of the NAD(+) recognition
      locus common in dehydrogenases. Site-directed mutagenesis and enzyme kinetic
      assays were performed to assess the role of different residues in metal,
      cofactor, and substrate binding. In contrast to previous assumptions, the
      essential His267 residue does not interact with the metal ion. Asp39 appears to
      be the key residue for discriminating against NADP(+). Modeling L-1,2-propanediol
      in the active center resulted in a close approach of the C-1 hydroxyl of the
      substrate to C-4 of the nicotinamide ring, implying that there is a typical metal
      dependent dehydrogenation catalytic mechanism.

PMID- 15995210
TI  - Low-molecular-weight protein tyrosine phosphatases of Bacillus subtilis.
AB  - In gram-negative organisms, enzymes belonging to the low-molecular-weight protein
      tyrosine phosphatase (LMPTP) family are involved in the regulation of important
      physiological functions, including stress resistance and synthesis of the
      polysaccharide capsule. LMPTPs have been identified also in gram-positive
      bacteria, but their functions in these organisms are presently unknown. We cloned
      two putative LMPTPs from Bacillus subtilis, YfkJ and YwlE, which are highly
      similar to each other in primary structure as well as to LMPTPs from gram
      negative bacteria. When purified from overexpressing Escherichia coli strains,
      both enzymes were able to dephosphorylate p-nitrophenyl-phosphate and
      phosphotyrosine-containing substrates in vitro but showed significant differences
      in kinetic parameters and sensitivity to inhibitors. Transcriptional analyses
      showed that yfkJ was transcribed at a low level throughout the growth cycle and
      underwent a sigma(B)-dependent transcriptional upregulation in response to
      ethanol stress. The transcription of ywlE was growth dependent but stress
      insensitive. Genomic deletion of each phosphatase-encoding gene led to a
      phenotype of reduced bacterial resistance to ethanol stress, which was more
      marked in the ywlE deletion strain. Our study suggests that YfkJ and YwlE play
      roles in B. subtilis stress resistance.

PMID- 15995212
TI  - Phenotypic and transcriptional characterization of the meningococcal PhoPQ
      system, a magnesium-sensing two-component regulatory system that controls genes
      involved in remodeling the meningococcal cell surface.
AB  - We previously identified and characterized a two-component regulatory system in
      the meningococcus with homology to the phoP-phoQ system in salmonella and showed
      that allele replacement of the NMB0595 regulator gene led to loss of virulence,
      sensitivity to antimicrobial peptides, perturbed protein expression, and
      magnesium-sensitive growth. On the basis of these findings we proposed that the
      system should be designated the meningococcal PhoPQ system. Here we further
      characterized the NMB0595 mutant and demonstrated that it had increased membrane
      permeability and was unable to form colonies on solid media with low magnesium
      concentrations, features that are consistent with disruption of PhoPQ-mediated
      modifications to the lipooligosaccharide structure. We examined the
      transcriptional profiles of wild-type and NMB0595 mutant strains and found that
      magnesium-regulated changes in gene expression are completely abrogated in the
      mutant, indicating that, similar to the salmonella PhoPQ system, the
      meningococcal PhoPQ system is regulated by magnesium. Transcriptional profiling
      of the mutant indicated that, also similar to the salmonella PhoPQ system, the
      meningococcal system is involved in control of virulence and remodeling of the
      bacterial cell surface in response to the host environment. The results are
      consistent with the hypothesis that the PhoP homologue plays a role in the
      meningococcus similar to the role played by PhoP in salmonella. Elucidating the
      role that the PhoPQ system and PhoPQ-regulated genes play in the response of the
      meningococcus to the host environment may provide new insights into the
      pathogenic process.

PMID- 15995213
TI  - PhoR1-PhoP1, a third two-component system of the family PhoRP from Myxococcus
      xanthus: role in development.
AB  - The pair PhoR1-PhoP1 is the third two-component system of the family PhoRP
      reported in M. xanthus. PhoR1 is a histidine kinase anchored to the membrane
      through a transmembrane domain located in the amino-terminal portion of the
      protein. As a result, 93% of the protein is located in the cytoplasm. This
      topology is unusual in the PhoR-type histidine kinases. PhoP1 is a response
      regulator with a helix-loop-helix motif typical of the DNA-binding proteins.
      Although the operon phoPR1 is expressed during vegetative growth, it peaks during
      development. The expression levels of this operon are higher in phosphate
      containing media than in those in which the nutrient is absent. A deletion mutant
      in this system exhibits a delay in aggregation and the formation of fruiting
      bodies larger than those of the wild-type strain. The expression of the operon is
      autoregulated. This system is also partially responsible for the expression of Mg
      independent acid and neutral phosphatases, but it is not required for the
      expression of alkaline phosphatases.

PMID- 15995214
TI  - Systematic characterization of the ADP-ribose pyrophosphatase family in the
      Cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - We have characterized four putative ADP-ribose pyrophosphatases Sll1054, Slr0920,
      Slr1134, and Slr1690 in the cyanobacterium Synechocystis sp. strain PCC 6803.
      Each of the recombinant proteins was overexpressed in Escherichia coli and
      purified. Sll1054 and Slr0920 hydrolyzed ADP-ribose specifically, while Slr1134
      hydrolyzed not only ADP-ribose but also NADH and flavin adenine dinucleotide. By
      contrast, Slr1690 showed very low activity for ADP-ribose and had four
      substitutions of amino acids in the Nudix motif, indicating that Slr1690 is not
      an active ADP-ribose pyrophosphatase. However, the quadruple mutation of Slr1690,
      T73G/I88E/K92E/A94G, which replaced the mutated amino acids with those conserved
      in the Nudix motif, resulted in a significant (6.1 x 10(2)-fold) increase in the
      k(cat) value. These results suggest that Slr1690 might have evolved from an
      active ADP-ribose pyrophosphatase. Functional and clustering analyses suggested
      that Sll1054 is a bacterial type, while the other three and Slr0787, which was
      characterized previously (Raffaelli et al., FEBS Lett. 444:222-226, 1999), are
      phylogenetically diverse types that originated from an archaeal Nudix protein via
      molecular evolutionary mechanisms, such as domain fusion and amino acid
      substitution.

PMID- 15995215
TI  - The genome of Sulfolobus acidocaldarius, a model organism of the Crenarchaeota.
AB  - Sulfolobus acidocaldarius is an aerobic thermoacidophilic crenarchaeon which
      grows optimally at 80 degrees C and pH 2 in terrestrial solfataric springs. Here,
      we describe the genome sequence of strain DSM639, which has been used for many
      seminal studies on archaeal and crenarchaeal biology. The circular genome carries
      2,225,959 bp (37% G+C) with 2,292 predicted protein-encoding genes. Many of the
      smaller genes were identified for the first time on the basis of comparison of
      three Sulfolobus genome sequences. Of the protein-coding genes, 305 are exclusive
      to S. acidocaldarius and 866 are specific to the Sulfolobus genus. Moreover, 82
      genes for untranslated RNAs were identified and annotated. Owing to the probable
      absence of active autonomous and nonautonomous mobile elements, the genome
      stability and organization of S. acidocaldarius differ radically from those of
      Sulfolobus solfataricus and Sulfolobus tokodaii. The S. acidocaldarius genome
      contains an integrated, and probably encaptured, pARN-type conjugative plasmid
      which may facilitate intercellular chromosomal gene exchange in S.
      acidocaldarius. Moreover, it contains genes for a characteristic restriction
      modification system, a UV damage excision repair system, thermopsin, and an
      aromatic ring dioxygenase, all of which are absent from genomes of other
      Sulfolobus species. However, it lacks genes for some of their sugar transporters,
      consistent with it growing on a more limited range of carbon sources. These
      results, together with the many newly identified protein-coding genes for
      Sulfolobus, are incorporated into a public Sulfolobus database which can be
      accessed at http://dac.molbio.ku.dk/dbs/Sulfolobus.

PMID- 15995216
TI  - Localization of translocation complex components in Bacillus subtilis: enrichment
      of the signal recognition particle receptor at early sporulation septa.
AB  - We here demonstrate that in Bacillus subtilis, the signal recognition particle
      receptor, FtsY, transiently localizes to early sporulation septa, whereas three
      SecYEG translocase-associated membrane proteins (SecDF, SpoIIIJ, and YqjG) are
      uniformly distributed. These results suggest FtsY delivers secreted proteins to
      SecYEG at the septum, consistent with initial septal localization of forespore
      membrane proteins.

PMID- 15995217
TI  - Extrachromosomal DNA of the symbiont Sodalis glossinidius.
AB  - The extrachromosomal DNA of Sodalis glossinidius from two tsetse fly species was
      sequenced and contained four circular elements: three plasmids, pSG1 (82 kb),
      pSG2 (27 kb), and pSG4 (11 kb), and a bacteriophage-like pSG3 (19 kb) element.
      The information suggests S. glossinidius is evolving towards an obligate
      association with tsetse flies.

PMID- 15995218
TI  - Characterization of the multiple transferable resistance repressor, MtrR, from
      Neisseria gonorrhoeae.
AB  - MtrR represses expression of the Neisseria gonorrhoeae mtrCDE multidrug efflux
      transporter genes. MtrR displays salt-dependent DNA binding, a stoichiometry of
      two dimers per DNA site, and, for a protein that was expected to be essentially
      all helical, a high percentage of random coil and possibly beta-sheet structure.

PMID- 15995219
TI  - Functional and topological analysis of the Burkholderia cenocepacia priming
      glucosyltransferase BceB, involved in the biosynthesis of the cepacian
      exopolysaccharide.
AB  - The BceB protein of the cystic fibrosis mucoid isolate Burkholderia cenocepacia
      IST432 is proposed to catalyze the first step of the exopolysaccharide repeat
      unit assembly. Extracts of Escherichia coli cells overexpressing BceB were shown
      to contain glycosyltransferase activity and mediate incorporation of glucose-1
      phosphate into membrane lipids. The amino acid sequence of BceB exhibits two
      conserved regions, one comprising two invariant aspartic acid residues (Asp339
      and Asp355) that are essential for catalysis, as substantiated by site-directed
      mutagenesis, and the other comprising a putative Rossmann fold motif. The results
      of protein topology analysis using PhoA and LacZ fusions supported in silico
      predictions that BceB has at least six transmembrane segments and two major
      cytoplasmic loops comprising the conserved regions described above.

PMID- 15995220
TI  - The gene encoding the glutamate dehydrogenase in Lactococcus lactis is part of a
      remnant Tn3 transposon carried by a large plasmid.
AB  - The gene responsible for the uncommon glutamate dehydrogenase (GDH) activity of
      Lactococcus lactis was identified and characterized. It encodes a GDH of family I
      that is mainly active in glutamate biosynthesis, is carried by a large plasmid,
      and is included, with functional cadmium resistance genes, in a remnant Tn3-like
      transposon.

PMID- 15995221
TI  - The F1Fo-ATP synthase of Mycobacterium smegmatis is essential for growth.
AB  - The F(1)F(o)-ATP synthase plays an important role in a number of vital cellular
      processes in plants, animals, and microorganisms. In this study, we constructed a
      DeltaatpD mutant of Mycobacterium smegmatis and demonstrated that atpD encoding
      the beta subunit of the F(1)F(o)-ATP synthase is an essential gene in M.
      smegmatis during growth on nonfermentable and fermentable carbon sources.

PMID- 15995222
TI  - EspC is involved in controlling the timing of development in Myxococcus xanthus.
AB  - The espC null mutation caused accelerated aggregation and formation of tiny
      fruiting bodies surrounded by spores, which were also observed in the espA mutant
      and in CsgA-overproducing cells in Myxococcus xanthus. In addition, the espC
      mutant appeared to produce larger amounts of the complementary C-signal than the
      wild-type strain. These findings suggest that EspC is involved in controlling the
      timing of fruiting body development in M. xanthus.

PMID- 15995223
TI  - Adenylyl cyclase activity of Cya1 from the cyanobacterium Synechocystis sp.
      strain PCC 6803 is inhibited by bicarbonate.
AB  - Bicarbonate stimulates the activities of several class III adenylyl cyclases
      studied to date. However, we show here that bicarbonate decreased V(max) and
      substrate affinity in Cya1, a major adenylyl cyclase in the cyanobacterium
      Synechocystis sp. strain PCC 6803. This indicates that manifestation of the
      bicarbonate responsiveness is specifically modulated in Cya1.

PMID- 15995225
TI  - Photoresponsive flagellum-independent motility of the purple phototrophic
      bacterium Rhodobacter capsulatus.
AB  - We report the discovery of photoresponsive, flagellum-independent motility of the
      alpha-proteobacterium Rhodobacter capsulatus, a nonsulfur purple phototrophic
      bacterium. This motility takes place in the 1.5% agar-glass interface of petri
      plates but not in soft agar, and cells move toward a light source. The
      appearances of motility assay plates inoculated with wild-type or flagellum
      deficient mutants indicate differential contributions from flagellar and
      flagellum-independent mechanisms. Electron microscopy confirmed the absence of
      flagella in flagellar mutants and revealed the presence of pilus-like structures
      at one pole of wild-type and mutant cells. We suggest that R. capsulatus utilizes
      a flagellum-independent, photoresponsive mechanism that resembles twitching
      motility to move in a line away from the point of inoculation toward a light
      source.

PMID- 15995224
TI  - Identification of nlmTE, the locus encoding the ABC transport system required for
      export of nonlantibiotic mutacins in Streptococcus mutans.
AB  - Streptococcus mutans UA159, the genome sequence reference strain, exhibits
      nonlantibiotic bacteriocin (mutacin) activity. In this study, we have combined
      bioinformatic and mutational analyses to identify the ABC transporter designated
      NlmTE, which is required for mutacin biogenesis in strain UA159 as well as in
      another mutacin producer, S. mutans N.

PMID- 15995227
TI  - Chemotactic responses to metals and anaerobic electron acceptors in Shewanella
      oneidensis MR-1.
AB  - Although a previous study indicated that the dissimilatory metal-reducing
      bacterium Shewanella oneidensis MR-1 lacks chemotactic responses to metals that
      can be used as anaerobic electron acceptors, new results show that this bacterium
      responds to both Mn(III) and Fe(III). Cells were also shown to respond to another
      unusual electron acceptor, the humic acid analog anthraquinone-2,6-disulfonate.
      These results indicate that S. oneidensis is capable of moving towards a number
      of unusual anaerobic electron acceptors, including some that would normally be
      insoluble in the environment. Additionally, S. oneidensis was shown to migrate in
      gradients of several divalent cations under anaerobic conditions. Although
      responses to the reduced forms of redox-active metals, such as Mn(II) and Fe(II),
      might indicate that S. oneidensis uses gradients of these metals to locate the
      insoluble electron acceptors Mn(III/IV) and Fe(III) for dissimilatory purposes,
      responses to non-redox-active metals, such as Zn(II), suggest that movement
      towards divalent cations might serve other, potentially assimilatory, purposes.

PMID- 15995226
TI  - Mutator effects in Escherichia coli caused by the expression of specific foreign
      genes.
AB  - Certain genes from Lactococcus lactis and Pseudomonas aeruginosa, including the
      nfxB gene, generate a mutator phenotype in Escherichia coli. The results of this
      study, together with those of a previous study, support conservation of
      regulatory sequences in E. coli and P. aeruginosa and suggest that some efflux
      pumps prevent mutagenicity by exporting mutagenic products of metabolism.

PMID- 15995236
TI  - Factors associated with the wastage and achievements in competition of event
      horses registered in the United Kingdom.
AB  - The aims of this study were to estimate the wastage of horses registered for
      eventing in Britain, to investigate the reasons for this wastage and to evaluate
      factors affecting the horses' achievement of grade I status (at least 61 points)
      while registered. An analysis of the database of the British Eventing register
      found that 33.7 per cent of horses registered for the first time in 1999 were not
      re-registered for eventing in subsequent years. By using multivariable logistic
      regression analysis, it was shown that horses that were kept at an event yard
      were more likely to be re-registered than those kept on other premises (odds
      ratio [or] 2.0, 95 per cent confidence interval [ci] 1.2 to 3.2), and those that
      took part in showjumping while registered were also more likely to be re
      registered (or 1.5, 95 per cent ci 1.1 to 2.2). Horses that took part in
      unaffiliated eventing while registered were less likely to be re-registered the
      following year (or 0.7, 95 per cent ci 0.5 to 0.9), as were those that were not
      insured (or 0.7, 95 per cent ci 0.5 to 1.0) and those from outside the British
      Isles (or 0.6, 95 per cent ci 0.3 to 1.0). Veterinary problems were the most
      commonly cited explanation (35.1 per cent) why horses that remained in their
      original ownership were not re-registered with British Eventing the following
      year. Horses from Australia were more likely to achieve grade I status than
      horses from the British Isles (or 9.7, 95 per cent ci 7.1 to 13.2), as were
      horses from New Zealand (or 6.4, 95 per cent ci 5.0 to 8.2), the usa (or 5.2, 95
      per cent ci 3.8 to 7.2) and France (or 2.8, 95 per cent ci 2.1 to 3.7), but
      horses from the Netherlands (or 0.5, 95 per cent ci 0.3 to 0.9) and Belgium (or
      0.3, 95 per cent ci 0.1 to 0.9) were less likely to achieve grade I status. Mares
      were less likely to achieve grade I status than geldings (or 0.4, 95 per cent ci
      0.4 to 0.5).

PMID- 15995228
TI  - Effect of sdiA on biosensors of N-acylhomoserine lactones.
AB  - Many gram-negative bacteria synthesize N-acylhomoserine lactones (AHLs) and then
      use transcription factors of the LuxR family to sense and respond to AHL
      accumulation in the environment; this phenomenon is termed quorum sensing.
      Bacteria produce a variety of AHLs, and numerous bacterial reporter strains, or
      biosensors, that can detect subsets of these molecules have been constructed.
      Many of these are based on Escherichia coli because this species does not produce
      AHLs. However, both Escherichia and Salmonella spp. contain a LuxR homolog named
      SdiA that can detect exogenous AHL synthesized by other microbial species. In
      this study we have determined that sdiA of E. coli and Salmonella spp. can
      activate an RhlR-based biosensor plasmid in response to AHLs other than what the
      biosensor was designed to detect. SdiA does not activate LuxR-, LasR-, or AhyR
      based biosensor plasmids, although the presence of sdiA in E. coli does interfere
      with the function of the AhyR-based biosensor. Because sdiA interferes with the
      function of two of the four reporters, we have constructed a set of E. coli
      biosensor strains that lack sdiA. The set includes control reporters that allow
      the luxR dependence of responses to be determined.

PMID- 15995237
TI  - Outbreaks of infectious keratoconjunctivitis in alpine chamois and ibex in
      Switzerland between 2001 and 2003.
AB  - Five outbreaks of infectious keratoconjunctivitis (ikc) affecting alpine chamois
      and ibex in the western and central Swiss Alps were recorded in 2001 to 2003.
      Mycoplasma conjunctivae was identified from conjunctival swabs by means of a
      nested pcr in 27 of the 28 chamois tested. The outbreaks occurred in an area
      covering 1590 km(2). Deep valleys acted as a barrier to the spread of the
      disease. A total of 409 chamois and 33 ibex with clinical signs of ikc were
      reported. Most of the chamois were shot, primarily because they were blind or in
      poor general body condition. Almost a quarter were observed alive, and 16.9 per
      cent died as a result of ikc. Many of the affected animals were juveniles, and
      more females than males died of ikc. The disease was more common during the
      summer and autumn. The chamois affected by ikc were found at altitudes between
      550 and 3200 m. The estimated overall mortality was less than 5 per cent, but
      more than 20 per cent may have died locally. Ibex affected by ikc were recorded
      in only two outbreaks. In six places, ibex with clinical signs of ikc were found
      before the first affected chamois appeared in the same area.

PMID- 15995238
TI  - Protection of dogs for 13 months against Bordetella bronchiseptica and canine
      parainfluenza virus with a modified live vaccine.
AB  - Twelve specific pathogen-free (spf) puppies were vaccinated intranasally with a
      bivalent, modified live vaccine against infectious tracheobronchitis (group 1)
      and six puppies of the same age and from the same source served as unvaccinated
      controls (group 2). Both groups were challenged with wild-type Bordetella
      bronchiseptica and canine parainfluenza virus by the aerosol route 56 weeks after
      group 1 had been vaccinated, and at the same time six 10-week-old spf puppies
      from the same source (group 3) were also challenged. Oronasal swabs were taken
      regularly before and after the challenge, for the isolation of bacteria and
      viruses, and the dogs were observed for clinical signs for three weeks after the
      challenge. The control dogs became culture-positive for B bronchiseptica and
      canine parainfluenza virus, but the isolation yields from the vaccinated group
      were significantly lower (P<0.05). The mean clinical scores of the vaccinated
      group were 61 per cent lower than the scores of group 2 (P=0.009), and 90 per
      cent lower than the scores of group 3 (P=0.001).

PMID- 15995239
TI  - Possible new Chlamydophila species causing chlamydiosis in farmed Nile crocodiles
      (Crocodylus niloticus).

PMID- 15995240
TI  - Ultrasonographic findings in three cows with cellulitis.

PMID- 15995241
TI  - Recent spread of FMD virus serotype Asia 1.

PMID- 15995243
TI  - Prevalence of gastrointestinal parasites in horses.

PMID- 15995244
TI  - Surveillance for equine diseases.

PMID- 15995245
TI  - Fatal Haemoproteus psittaci infection in an African grey parrot.

PMID- 15995246
TI  - Extracranial meningioma in a dairy cow.

PMID- 15995247
TI  - Protecting a veterinary grave in Kenya.

PMID- 15995248
TI  - Identifying and engineering ion pairs in adenylate kinases. Insights from
      molecular dynamics simulations of thermophilic and mesophilic homologues.
AB  - Molecular dynamics simulations were performed to study thermal stabilization of
      proteins via electrostatic interactions of ion pairs. Dynamic motions of four ion
      pairs previously proposed to be important in thermal stability of adenylate
      kinase from the thermophile Bacillus stearothermophilus were monitored during the
      simulation. One of the four ion pairs identified in the crystal structure, Lys180
      Asp114, was not maintained in close contact suggesting that the ion pair does not
      contribute to thermal stability. Among the other three ion pairs, the ion pair
      Arg116-Glu198 was proposed to be the most important for stability. To predict
      behaviors of the ion pairs when engineered into a mesophilic homologue to
      increase stability, in silico mutants of adenylate kinase from the mesophile
      Bacillus subtilis were generated, and their molecular dynamics simulations were
      carried out. The ion pairs in the mutant simulations displayed similar behaviors
      to those in the simulation of the thermophilic protein. To validate the results
      of the simulations experimentally, the same mutants were produced in vitro and
      their thermal stabilities were measured using differential scanning calorimetry.
      In agreement with the simulations, the Lys180-Asp114 did not result in any
      increase in stability by itself or additive effect with other ion pairs, whereas
      a mutant with the Arg116-Glu198 exhibited the highest stability among the mutants
      having one of the four ion pairs. These results provide specific knowledge about
      stability in adenylate kinases and more generally suggest that molecular dynamics
      simulations can provide valuable information for identifying and engineering ion
      pairs.

PMID- 15995252
TI  - Automation: humans versus machines?

PMID- 15995249
TI  - Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase
      and stimulates its exonuclease activity.
AB  - Nuclear DNA helicase II (NDH II), alternatively named RNA helicase A, is involved
      in transcription and RNA processing. Here, we report that NDH II interacts with
      the Werner syndrome helicase WRN, an enzyme associated with premature aging and
      predisposition to tumorigenesis. NDH II was co-purified with WRN, DNA polymerase
      delta, and replication protein A (70 kDa) during several steps of conventional
      column chromatography. Co-immunoprecipitations revealed an association between
      NDH II, WRN, and polymerase delta. We demonstrate a direct protein-protein
      interaction between WRN and NDH II that is mediated by the N-terminal double
      strand RNA-binding domain II and C-terminal RGG box of NDH II and the N-terminal
      exonuclease domain of WRN. WRN inhibited the DNA-dependent NTPase and DNA
      helicase activities of NDH II. On the other hand, the 3' --> 5' exonuclease
      activity of WRN was increased by the presence of NDH II. NDH II directly
      stimulated the exonuclease domain of WRN, whereas the exonuclease domain of WRN
      suppressed the DNA-dependent (but not RNA-dependent) ATPase activity of NDH II.
      These results suggest that the double-strand RNA-binding domain II and RGG box of
      NDH II together form a protein-protein interaction surface that contacts the
      exonuclease domain of WRN. Furthermore, NDH II enhanced the degradation of D-loop
      DNA by the WRN exonuclease. Taken together, these results suggest that NDH II
      plays a role in promoting the DNA processing function of WRN, which in turn might
      be necessary for maintaining genomic stability.

PMID- 15995253
TI  - Radioactivity in building materials used in and around Dhaka city.
AB  - The activity levels of (226)Ra, (232)Th and (40)K were determined using gamma-ray
      spectroscopy in different commercial brands of cement, sand and hollow concrete
      bricks, which were collected from the building material suppliers of Dhaka City.
      The activity concentrations in the samples were found to be somewhat higher than
      in other countries. An effort has been made to assess the radiation hazard
      associated with these materials by determining the gamma activity concentration
      index I. It was found that the value of I for all the samples was <or=2, which
      indicates that the gamma dose contribution was not more than 0.3 mSv y(-1). The
      samples considered were safe for use in the construction of urban dwellings in
      Bangladesh and do not pose any significant source of radiation hazard.

PMID- 15995254
TI  - The movement-specific effect of motor imagery on the premotor time.
AB  - The purpose of this study was to investigate the effect of motor imagery on the
      premotor time (PMT). Twelve healthy adults performed reaction time movements in
      response to external visual signals at rest, when holding an object (muscle
      activation), or performing different background imagined movements (motor
      imagery). When compared to rest, muscle activation reduced the PMT; imagined
      finger extension of the right hand and imagined finger flexion of the left hand
      elongated the PMT; imagined finger flexion of the right hand had no effect on the
      PMT. This movement-specific effect is interpreted as the sum of the excitatory
      effect caused by enhanced corticospinal excitability specifically for the primary
      mover of the imagined movement and an overall inhibition associated with
      increased task complexity during motor imagery. Our results clearly demonstrate
      that motor imagery has movement-specific effects on the PMT.

PMID- 15995255
TI  - Effects of response task on reaction time and the detection of affordances.
AB  - Studies on affordance perception commonly report systematic errors; a finding
      that is at odds with the observation that everyday motor behavior is accurate.
      The present study investigated whether the means by which perceptual performance
      is measured could explain the reported errors. Perception of overhead
      reachability and reaction time were measured using a verbal and an actual
      reaching response in a standing reach, and a reach-and-jump. Results show that
      participants accurately perceived their action boundaries for both tasks and in
      both response conditions. A simple reach, however, took less time to initiate
      (1,094 ms) than a reach-and jump (1,214 ms). Interestingly, the verbal response
      took considerably more time to initiate (1,424 ms) than the actual reach (1,154
      ms). These results suggest that making verbal judgments about affordances is a
      different task than actually acting on them. It is therefore concluded that the
      use of conscious judgments to measure perceptual performance should be considered
      with care.

PMID- 15995256
TI  - The effect of movement frequency on interlimb coupling during recumbent stepping.
AB  - During passive lower limb movement, active use of the upper limbs increases
      unintentional lower limb muscle activation. We hypothesized that faster movement
      frequencies would amplify lower limb muscle activation during upper limb exertion
      but would not affect lower limb muscle activation when the upper limbs were
      relaxed. We studied 10 healthy participants exercising on a recumbent stepping
      machine that mechanically coupled the four limbs via handles and pedals.
      Participants exercised at four frequencies (30, 60, 90, 120 steps/min) under four
      conditions of active and passive movement. Self-driven lower limb motion resulted
      in greater muscle activation compared to externally driven lower limb motion.
      Muscle activation amplitude increased with frequency for all conditions except
      for externally driven stepping. These results indicate that fast upper limb
      movement facilitates neuromuscular recruitment of lower limb muscles during
      stepping tasks. If a similar effect occurs in neurologically impaired individuals
      during active stepping, self-assisted exercise might enhance neuromuscular
      recruitment during rehabilitation.

PMID- 15995257
TI  - Coupling of force variability in bimanual tapping with asymmetrical force.
AB  - An experiment was conducted to examine the coupling of force variability in
      bimanual finger tapping sequences with asymmetrical forces. Right-handed
      participants were trained to produce bimanual finger tapping sequences consisted
      of an intertap interval of 500 ms and eight force conditions: two alternating
      force left high, two alternating force right high, two simultaneous force left
      high, and two simultaneous force right high conditions. During practice, visual
      force feedback was provided for both hands performing the bimanual tapping
      sequences. After practice, the participants produced the learned tapping
      sequences in the absence of feedback. Most importantly, whereas the peak force
      variability of the nondominant left hand was larger than that of the dominant
      right hand under the right high conditions, there was no left-right difference
      under the simultaneous left high conditions. This suggests that under the
      simultaneous left high conditions, both hemispheres were activated, resulting in
      overflow in the right hand, and bringing the two force variabilities closer
      together.

PMID- 15995258
TI  - Speed-accuracy trade-off in voluntary postural movements.
AB  - We investigated the speed and accuracy of fast voluntary movements performed by
      the whole body during standing. Adults stood on a force plate and performed
      rhythmic postural movements generating fore and back displacements of the center
      of pressure (shown as online visual feedback). We observed that for the same
      target distance, movement time increased with the ratio between target distance
      and target width, as predicted by Fitts'-type relationships. For different target
      distances, however, the linear regressions had different slopes. Instead, a
      single linear relation was observed for the effective target width versus mean
      movement speed. We discuss this finding as a result of the pronounced inherent
      variability of the postural control system and when such a source of variability
      is considered, the observed relationship can be explained. The results reveal
      that the accuracy of fast voluntary postural movements is deteriorated by the
      variability due to sway during standing.

PMID- 15995259
TI  - Adaptation to separate kinematic and dynamic transformations in children and
      adults.
AB  - The question addressed in the present study is whether children and adults are
      able to combine and decompose separate kinematic (visual-feedback-shift) and
      dynamic (velocity-dependent force) transformations in goal-directed arm
      movements. A total of 64 participants (32 adults and 32 children) performed
      horizontal forearm movements using a single-joint arm manipulandum. When
      participants first learned kinematic and dynamic transformations separately,
      target error decreased in a subsequent combined transformation task. This effect
      was based on previous learning of the kinematic transformation. When they first
      learned the combined transformation, target error was smaller in the following
      kinematic-but not in the dynamic-transformation. No difference was found in
      adaptation performance between children and adults. The results suggest that
      there are two separate models for the kinematic and dynamic transformation and
      that a possible differentiation of kinematic and dynamic features of the motor
      task might already be present at age 11.

PMID- 15995260
TI  - Participatory research to promote physical activity at congregate-meal sites.
AB  - The purpose of this study was to determine the feasibility and effectiveness of
      an on-site physical activity (PA) program offered with congregate meals. Study 1
      surveyed meal-site users on their likelihood to participate. Study 2 used meal
      site-manager interviews and site visits to determine organizational feasibility.
      Study 3, a controlled pilot study, randomized meal sites to a 12-week group-based
      social-cognitive (GBSC) intervention or a standard-care control. Studies 1 and 2
      indicated that most meal-site users would participate in an on-site PA program,
      and meal sites had well-suited physical resources and strong organizational
      support for this type of program. In Study 3, GBSC participants increased their
      weekly PA over those in the control condition (p < .05, ES = .79). Results
      indicated that changes in task cohesion might have mediated intervention
      effectiveness. These studies demonstrate that a PA program offered in this venue
      is feasible, is effective in promoting PA, and could have a strong public health
      impact.

PMID- 15995261
TI  - A multilevel analysis of change in neighborhood walking activity in older adults.
AB  - The article reports on a multilevel analysis conducted to examine change in
      neighborhood walking activity over a 12-month period in a community-based sample
      of 28 neighborhoods of 303 older adults age 65 and over. The study employed a
      multilevel (residents nested within neighborhoods) and longitudinal (4 repeated
      measures over 1 year) design and a multilevel analysis of change and predictors
      of change in neighborhood walking activity. Results indicated a significant
      neighborhood effect, with neighborhood-level walking characterized by a downward
      trajectory over time. Inclusion of baseline variables using selected perceived
      neighborhood-level social- and physical-environment measures indicated that
      neighborhoods with safe walking environments and access to physical activity
      facilities had lower rates of decline in walking activity. The findings provide
      preliminary evidence of neighborhood-level change and predictors of change in
      walking activity in older adults. They also suggest the importance of analyzing
      change in physical activity in older adults from a multilevel or macrolevel
      framework.

PMID- 15995262
TI  - Biomechanics of the heel-raise exercise.
AB  - The purpose of this investigation was to determine whether increases in internal
      (muscular) demand would be proportional to increases in the external demand
      during heel-raise exercise. Seven male (mean age 74.9 +/- 4.8 years) and 9 female
      (mean age 74.4 +/- 5.1 years) older adults performed both double-leg heel raises
      and single-leg heel raises under 3 loading conditions (no external resistance and
      +5% and +10% of each participant's body weight). Kinematic and kinetic dependent
      variables were calculated using standard inverse-dynamics techniques. The results
      suggest that although the single-heel raise led to increases in peak net joint
      moments, power, and mechanical-energy expenditure (MEE), it did so at the expense
      of range of motion and angular velocity. In addition, increasing the external
      resistance by 5% of participants' body weight did not elicit significant changes
      in either the power or the MEE of the ankle joint. These effects should be
      considered when prescribing these exercises to older adults.

PMID- 15995263
TI  - Responses to walking-speed instructions: implications for health promotion for
      older adults.
AB  - This study examined the effect of age on descriptive walking-speed instructions
      commonly used in health promotion. Participants were 9 young (20-23 years) and 9
      older (75-83 years) women. Oxygen uptake and walking speed were measured in
      response to descriptive walking instructions ("slow," "comfortable," "brisk," and
      "fast"). Although the older women walked approximately 20% slower in response to
      all walking instructions and with significantly lower oxygen costs for brisk and
      fast, the intensity of the exercise represented a much greater percentage of
      VO2max and showed greater interindividual variation. When asked to walk at a
      brisk pace, the older women averaged 67% VO2max (SD 20.6), whereas the young
      women averaged only 45% VO2max (SD 4.5). With older people, brisk might elicit an
      exercise intensity unnecessarily high for physiological benefit and that might
      compromise safety and adherence, which emphasizes the need for validation of
      carefully worded exercise and training guidance for older adults.

PMID- 15995264
TI  - Physical-performance tests to evaluate mobility disability in community-dwelling
      elders.
AB  - The purposes of this study were to evaluate community-dwelling elderly adults
      with different levels of perceived mobility with 5 physical-performance tests,
      determine the cutoff values of the 5 tests, and identify the best tests for
      classifying mobility status. The community-mobility statuses of 203 community
      dwelling elders were classified as able, decreased, or disabled based on their
      self-reported ability to walk several blocks and climb stairs. They also
      performed the functional reach, timed 50-ft walk, timed 5-step, timed floor
      transfer, and 5-min-walk endurance tests. We found in all tests that the "able"
      outperformed the "decreased" and that the "decreased" outperformed the
      "disabled," except on the floor-transfer task. The optimum cutoff values of the 5
      performance tests were also reported. The 5-min walk and timed 5-step test could
      best separate the "able" from the "decreased," whereas the 50-ft-walk-test could
      best differentiate the "decreased" from the "disabled." The results suggest that
      community-mobility function of older adults can be captured by performance tests
      and that the cutoff values of the 5-min-walk, 5-step, and 50-ft-walk tests can be
      used in guiding intervention or prevention programs.

PMID- 15995265
TI  - Exercise intervention designed to improve strength and dynamic balance among
      community-dwelling older adults.
AB  - Loss of balance and falling are critical concerns for older adults. Physical
      activity can improve balance and decrease the risk of falling. The purpose of
      this study was to evaluate a simple, low-cost exercise program for community
      dwelling older adults. Sixteen senior adults were evaluated using the Senior
      Fitness Test for measures of functional strength, aerobic endurance, dynamic
      balance and agility, and flexibility. In addition, measures of height, weight,
      resting blood pressure, blood lipids, and cognitive function were obtained.
      Participants then attended a 10-week exercise class including stretching,
      strengthening, and balance-training exercises. At the completion of the program,
      significant improvements were observed in tests measuring dynamic balance and
      agility, lower and upper extremity strength, and upper extremity flexibility. The
      results indicate that exercise programs such as this are an effective, low-cost
      solution to improving health and factors that affect falling risk among older
      adults.

PMID- 15995266
TI  - The interaction of aging and 10 years of racing on ultraendurance running
      performance.
AB  - The aim of this study was to examine the interaction between aging and 10 years
      of racing in endurance runners. Race-time data from 194 runners who had completed
      10 consecutive 56-km ultramarathons were obtained. The runners were either 20.5
      +/- 0.7, 30.0 +/- 1.0, 39.9 +/- 0.9, or 49.4 +/- 1.0 years old at their first
      race. Each runner's race speed was determined for each race over the 10 years.
      Data were analyzed using repeated-measures ANOVA, one-way ANOVA, and independent
      t tests and showed that performance improved and declined at greater rates for
      younger runners; younger runners had a greater capacity for improvement than
      older runners; approximately 4 years were required to reach peak racing speed,
      regardless of age; it was not possible to compete at peak speed for more than a
      few years; and the combined effects of 10 years of aging and racing neither
      improve nor worsen net performance. In conclusion, these data suggest that
      although these runners showed similar patterns of change in race speed over a 10
      year period, the extent of change in performance was greater in younger than in
      older runners.

PMID- 15995267
TI  - Protein needs of older adults engaged in resistance training: a review.
AB  - Protein recommendations by some professional organizations for young adults
      engaged in resistance training (RT) are higher than the recommended dietary
      allowance (RDA), but recommendations for resistance-training older adults (>50
      years old) are not well characterized. Some argue that the current RDA is
      adequate, but others indicate increased protein needs. Although concerns have
      been raised about the consequences of high protein intake, protein intake above
      the RDA in older adults is associated with increased bone-mineral density when
      calcium intake is adequate and does not appear to compromise renal health in
      older individuals with normal renal function. Individual protein needs for older
      adults in RT are likely highly variable according to health and training regimen,
      but an intake of 1.0-1.3 g x kg(-1) x day(-1) should adequately and safely meet
      the needs of older adults engaged in RT, provided that their energy needs are
      met.

PMID- 15995268
TI  - Challenges in the management of visceral leishmaniasis.

PMID- 15995269
TI  - Truncal adiposity is present at birth and in early childhood in South Indian
      children.
AB  - OBJECTIVES: Muscle-thin but adipose ('thin-fat') body composition of south Asian
      adults contributes to their high risk of type 2 diabetes. Studies in Pune, India
      showed that this phenotype is present at birth. We aimed to determine if south
      Indian babies have a 'thin-fat' phenotype and if this persists in childhood.
      DESIGN: Prospective cohort study. SETTING: Holdsworth Memorial Hospital, Mysore,
      India. SUBJECTS: Children (n = 663) whose mothers were recruited from the
      antenatal clinics. METHODS: Weight, length, head, mid-upper-arm, abdominal
      circumferences; triceps and subscapular skinfolds were measured at birth, one and
      four years, and compared with white Caucasian babies born in Southampton, UK
      (birth), and UK and Dutch growth standards (one and four years). RESULTS: Mysore
      babies were lighter (2983 g vs 3472 g; -1.10 SD, CI -1.16, -1.02) and smaller in
      all body measurements than UK neonates (P < 0.001). The deficit was greatest for
      mid-upper-arm (-1.07 SD), head (-0.89 SD) and abdominal circumferences (-0.73
      SD), and least for length (-0.25 SD) and subscapular skinfold thickness (-0.19
      SD). Predictors of skinfold thickness were maternal body mass index (P < 0.001)
      and socio-economic status (P = 0.05). At four years, subscapular skinfold
      thickness was larger than UK (+0.18 SD, CI +0.11, +0.25; P < 0.001) and Dutch
      standards (+0.61 SD, CI +0.51, +0.71; P < 0.001), despite all other body
      measurements remaining smaller. Predictors of 4-year skinfold thickness were
      neonatal skinfold thickness (P = 0.001) and maternal insulin concentrations (P =
      0.05). CONCLUSIONS: Mysore newborns have a 'thin-fat' phenotype. This may reflect
      the action of genes and/or the 'maternal environment'. The phenotype persists in
      childhood, and may be the forerunner of a diabetogenic adult phenotype.

PMID- 15995270
TI  - Non-specific effect of measles vaccination on all-cause child mortality:
      revisited.

PMID- 15995271
TI  - Meningococcal disease--outbreak in Delhi.
AB  - Meningococcal disease occurs both endemically and epidemically across the world.
      In India also meningococcal disease occurs sporadically with epidemics occurring
      at regular intervals. Epidemics of meningococcal disease have occurred in Delhi
      in the year 1935, then in the year 1966 which lasted for a year and again in 1985
      86. The last epidemic took a great toll with case fatality rate nearly 13%. This
      year also there has been an outbreak of meningococcal disease with nearly 400
      cases and case fatality rates of about 10% majority are males between the age
      group of 21-30 years and from the inner crowded areas of the city.

PMID- 15995272
TI  - Chest physiotherapy in pediatric practice.
AB  - Chest physiotherapy (CPT) in children is generally considered as a separate and
      specialized treatment modality that should be rendered only by a physiotherapist.
      Actually this is not difficult if one has a proper understanding of the basic
      concept and principle behind the maneuver. This article aims at making CPT
      simple, so that it could be incorporated in routine pediatric practice for
      managing respiratory ailments.

PMID- 15995273
TI  - Cord blood analysis for prenatal diagnosis of thalassemia major and hemophilia A.
AB  - Beta thalassemia and Hemophilia A are common genetic disorders for which prenatal
      diagnosis (PND) is an accepted option. Our aim was to evaluate cord blood
      analysis as a method for PND of these disorders. Cord blood samples at 18-26
      weeks gestation from nine mothers with previous thalassemia major child and five
      families with previous hemophilia A were studied. In the former; HbF, HbA2 and
      HbF were determined by high performance liquid chromatography (HPLC) and in
      latter; Factor VIII and IX assays were done by one stage method. In HPLC studies
      for thalassemia, three out of nine fetuses were affected, five were carriers and
      one was normal. In hemophilia PND samples, 2 out of five fetuses were affected.
      Thus, HPLC and factor VIII assay in cord blood are feasible alternatives for PND
      in Beta thalassemia and hemophilia A respectively, especially when DNA analysis
      is uninformative or there are financial constraints.

PMID- 15995274
TI  - Deliberate self-poisoning in children.
AB  - This prospective study was aimed to analyze the nature of and the factors
      associated with deliberate self-poisoning in children below the age of 12 years.
      Children referred to the Child Guidance Clinic for evaluation after recovery from
      the effects of poisoning during the five-year period between 1999 and 2003 formed
      the subjects of the study. The children were evaluated for stress factors,
      psychiatric disorders and the nature and mode of deliberate self-poisoning.
      Deliberate self-poisoning constituted 0.9% of total admissions due to poisoning.
      There were 10 boys and 2 girls between the ages of 9 and 12 years. Both acute and
      chronic stress in the family and school were associated with deliberate self
      poisoning. Majority of them had psychiatric disorders. Rat poison (zinc
      phosphide) was the commonest poison used. Two children got the idea from watching
      TV serials.

PMID- 15995275
TI  - Prevalence of fatty liver in non-obese Japanese children with atopic dermatitis.
AB  - Fatty liver in non-obese Japanese children was observed in 3.2% of non-atopic
      children and in 17.6% of patients with atopic dermatitis in 2000. The prevalence
      of fatty liver in non-obese children aged 0-12 years was studied from 2001 to
      2003. Subjects were either non-atopic children, or suffering from bronchial
      asthma, allergic rhinitis, or atopic dermatitis. Fatty liver was studied by
      abdominal ultrasound scans. The prevalence of fatty liver was increasing
      annually, and it reached to 12.5% in non-atopic children, 13.1% in patients with
      bronchial asthma, 13.7% in patients with allergic rhinitis, or 33.9% in patients
      with atopic dermatitis, in 2003. Since fatty liver in childhood may be a risk
      factor for lifestyle-related diseases in future, care should be taken to prevent
      it.

PMID- 15995276
TI  - Prevalence of anemia among school going adolescents of Chandigarh.
AB  - This study was conducted to assess the prevalence of anemia and determine serum
      ferritin status among 1120 apparently healthy adolescents (12 to 18 years)
      sampled from 11 city and 2 rural schools in Chandigarh. All the boys and the
      girls were subjected to anthropometric examination and hemoglobin estimation. The
      estimation of hemoglobin was done by cyanmethemoglobin method. Serum ferritin was
      estimated by ELISA (UB1 Magiwel enzyme immuno assay) method in 183 students. The
      overall prevalence of anemia calculated as per WHO Guidelines was significantly
      higher among girls (23.9%) as compared to boys (odds ratio--3.75, 95% CI--2.59 to
      5.43, P < 0.01). Anemia was observed more in rural (25.4%) as compared to urban
      (14.2%) adolescents (OR--0.49, 95% CI--0.34 to 0.70, P < 0.01). Iron stores
      estimated by serum ferritin in 183 subjects were deficient in 81.7% and 41.6% of
      the adolescent girls and boys, respectively.

PMID- 15995277
TI  - Congenital brucellosis in a preterm neonate.
AB  - Brucellosis is primarily a zoonotic infection. Transmission to humans occurs
      through direct contact with infected animals or consumption of infected animal
      products. Human to human transmission is rare, but has been reported in
      association with blood transfusion, bone marrow transplantation, transplacental
      or perinatal exposure, during sexual intercourse and postnatally through breast
      milk. This report presents a case of transplacentally transmitted neonatal
      brucellosis.

PMID- 15995278
TI  - Pseudo-hypo aldosteronism Type II.
AB  - A 50-day-old infant diagnosed as meningitis had persistently elevated serum
      potassium, low serum bicarbonate and normal serum sodium. She had metabolic
      acidosis with low TTKG, low serum renin and low normal serum aldosterone with no
      renal failure or extra renal causes of hyperkalemia. Hence a diagnosis of Type II
      pseudo-hypoaldosteronism was made. She was started on oral thiazide following
      which her serum electrolytes normalized.

PMID- 15995279
TI  - Proboscis lateralis.

PMID- 15995280
TI  - Hereditary sensory and autonomic neuropathy type IV.

PMID- 15995281
TI  - Hereditary spherocytosis in a family from Tamil Nadu.

PMID- 15995282
TI  - Hypophosphatemic rickets with epidermal nevus syndrome.

PMID- 15995283
TI  - Primary torsion of the greater omentum.

PMID- 15995284
TI  - Treatment dilemma in osteopetrorickets.

PMID- 15995286
TI  - Psychogenic diarrhea.

PMID- 15995285
TI  - Congenital adrenal hypoplasia presenting as severe respiratory failure.

PMID- 15995287
TI  - Natural antioxidant therapy for patients with hemolytic anemia.

PMID- 15995289
TI  - Painful mononeuritis multiplex in idiopathic thrombocytopenic purpura.

PMID- 15995291
TI  - [Molecular mechanisms of bone formation and bone-forming factors].
AB  - Osteoblast is a specialized cell that forms bone tissue. The process of bone
      formation by osteoblasts is divided into several steps such as differentiation of
      cells, secretion of matrix proteins, mineralization of osteoid, and bone
      coupling. Although each step supposed to be controlled by various factors, the
      regulatory mechanisms of bone formation is unclear. Recently, a central control
      system of bone formation was identified. These findings will be useful to develop
      novel bone-forming drugs.

PMID- 15995290
TI  - [The molecular mechanism of osteoclastic bone resorption and inhibitory drugs for
      bone resorption].
AB  - Osteoclasts are the only cells that destroy and resorb bone. The differentiation
      and activation of osteoclasts are tightly regulated by osteoblasts. Osteoblasts
      express RANKL essential for osteoclast differentiation. Osteoclast precursors
      express RANK, a receptor of RANKL, recognized RANKL through cell-cell
      interaction. Serum levels of RANKL were markedly elevated in deficiency of
      osteoprotegerin (OPG), a soluble decoy receptor for RANKL. Calcitonin and
      bisphosphonate are used for inhibitory drugs of bone resorption by osteoclasts.
      In addition, a specific anti-RANKL monoclonal antibody is expected as well
      tolerated bone antiresorptive agent.

PMID- 15995292
TI  - [Recent progress of pathogenesis and treatments in rheumatoid arthritis].
AB  - Bone homeostasis is maintained by a balance between bone resorption by
      osteoclasts and bone formation by osteoblasts. Osteoclast maturation requires
      stimulation by RANKL expressed on osteoblasts and other cells. During the
      processes, pro-inflammatory cytokines such as TNF-alpha cause an imbalance in
      bone metabolism via direct and/or indirect effects on osteoclasts. These
      inflammatory signals originate from the immune system, the largest source of cell
      derived regulatory signals and such immunological signals to the bone results in
      secondary osteoporosis and bone destruction. Actually, such phenomena mainly
      occur at the interface between proliferating synovium and bone tissue in
      rheumatoid arthritis (RA). Thus, therapeutic strategies using biologics including
      infliximab and etanercept, effective for treating RA disease activity, also
      reduce joint destruction. Based on an improved understanding of immune signals,
      investigation of the suppression of cell functions may lead to improved
      understanding and better treatment of bone destruction and osteoporosis.

PMID- 15995293
TI  - [Mechanism and treatment of cancer metastasis to bone].
AB  - Bone is one of the most preferential metastatic target sites for 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 for them to arrest,
      survive and proliferate. In particular, the production of bone-resorbing
      cytokines by these cancer cells increases osteoclastic bone resorption, which in
      turn facilitates the colonization of these cancer cells in bone through abundant
      supplies of bone-stored growth factors. This crosstalk between metastatic cancer
      cells and bone promotes the development and progression of bone metastases.
      Disruption of this vicious cycle using bisphosphonates will allow us to
      effectively and specifically inhibit bone metastases.

PMID- 15995294
TI  - [Possible roles of gene deficient mice as a model of osteoporosis].
AB  - Recent technical advance for making of gene modified mice includes gene targeting
      and transgenic mice are clarify the biological function of its targeted
      molecules. The evidence from gene modified mice on sex-steroid hormones may
      contribute to develop clinical drugs for osteoporosis treatment especially. Gene
      deficient mice of the sole enzyme for estrogen synthesis (aromatase), estrogen
      receptor and androgen receptor deficient mice have great potential to elucidate
      further mechanisms of pathogenesis of osteoporosis.

PMID- 15995295
TI  - [FGF23 and bone metabolism].
AB  - Fibroblast growth factor (FGF) 23 was recently shown to alter serum phosphate
      level by modulating renal tubular phosphate reabsorption and production of active
      vitamin D independently of parathyroid hormone action. In addition, FGF23 was
      shown to be involved in the development of several diseases including autosomal
      dominant hypophosphatemic rickets/osteomalacia (ADHR), X-linked hypophosphatemic
      rickets/osteomalacia (XLH) and tumor-induced rickets/osteomalacia (TIO). It has
      also been suggested that FGF23 physiologically regulates serum phosphate level
      because FGF23 null mice show high serum concentration of phosphate.

PMID- 15995296
TI  - [Vitamin K2 and bone quality].
AB  - Effects of vitamin K(2) (menatetrenone) and alendronate on bone mineral content
      and bone mechanical property in rats fed a low-magnesium diet. Recent clinical
      studies have shown that the occurrence of new fractures does not always depend on
      bone mineral density. Therefore bone quality has become an important issue in
      osteoporosis research. No animal model for evaluating bone quality has been
      established. In this study, we found that the treatment of rats with a low
      magnesium (Mg) diet reduced their bone strength without decreasing bone mineral
      content (BMC), so the low Mg diet model is considered to be a good model for
      examining bone quality. Using this model, we investigated the effects of vitamin
      K(2) (V.K(2)) and alendronate (ALN). V.K(2) increased maximum load and elastic
      modulus without influencing BMC. ALN increased maximum load with increasing BMC.
      By using Fourier transform infrared microscopic analysis, the low-Mg diet
      treatment increased the mineral/matrix ratio of bones, and V.K(2) suppressed the
      increase in this ratio. These findings suggest that the mineral/matrix ratio may
      be a factor involved in bone quality, and that V.K(2) may improve bone quality.

PMID- 15995297
TI  - [The interplay of magnesium and vitamin K2 on bone mineralization].
AB  - Magnesium (Mg) is most likely restored in bone matrix, implicating a pivotal role
      in bone mineralization. Mg-insufficient bone reveals fragility to mechanical
      loading despite normal or higher levels of bone mineral content, permitting
      stimulated osteoclastic bone resorption. In contrast, vitamin K(2) (MK
      4:menatetrenone) inhibited osteoclastic bone resorption stimulated by the Mg
      insufficiency, thereby normalizing bone remodeling. The Mg-insufficiency caused
      an increased concentration of calcium, which resulted in an extremely-high purity
      of hydroxyapatite (HA) crystal [Ca(10)(PO(4))(6)(OH)(2)] and accelerated
      mineralization in bone. In contrast, MK-4 did not affect the calcium
      concentration nor HA-purity, but repressed mineralization accelerated by Mg
      insufficiency. Thus, MK-4 appears to recover the "bone quality" lessened by the
      Mg-insufficiency by two mechanisms:controlling bone turnover and mineralization.

PMID- 15995298
TI  - [A novel therapeutic vaccine approach against RANKL that prevents pathological
      bone destruction].
AB  - The vaccination method is used to induce antibody response against disease
      related proteins by immunization with modified pathological antigen as preventive
      therapy to acquire disease resistance. A RANKL vaccine was developed by modifying
      the soluble TNF-like domain of murine RANKL to incorporate a promiscuous Th
      epitope. Immunization with RANKL vaccine prevented pathological bone resorption
      in arthritic mice or ovariactomized mice.

PMID- 15995299
TI  - [Local application of statin for bone augmentation].
AB  - It has been reported that statin, an inhibitor of cholesterol synthesis, enhances
      bone formation by stimulating osteoblastic differentiation and function and that
      it also inhibits bone resorption by osteoclasts. Although the potentiality of
      statin as a therapeutic drug for osteoporosis has been expected, the clinical
      evidences supporting this potentiality are few. On the other hand, there are
      several reports demonstrating that local application of statin promotes bone
      augmentation and bone regeneration. The history of statin as a therapeutic drug
      for hypercholesterolemia is long and the toxicity of this drug has been well
      examined. Thus, it is unlikely that local application of this drug at low dose
      will induce serious side effects. It is possible that local bone augmentation
      with statin will appear clinically in the near future if proper local drug
      delivery system for statin is developed.

PMID- 15995300
TI  - [Regulation of hematopoiesis by the osteoblastic niche].
AB  - Blood cell production is maintained throughout the lifetime of an individual by
      hematopoietic stem cells (HSCs). Interaction of HSCs with their particular
      microenvironments, known as stem cell niches, is critical for maintaining the
      stem cell properties, including self-renewal capacity and the ability of
      differentiation into single or multiple lineages. Recently, it was clarified that
      a osteoblast is a critical component of the niche for HSCs. HSCs keep balance
      between quiescence and cell division/proliferation in the osteoblastic niche. The
      HSC specific properties are dynamically controlled by the signalings of
      receptors/ligands and cell adhesion molecules produced by osteoblasts.

PMID- 15995301
TI  - [The possibility of tooth regenerative therapy].
AB  - Teeth develop from the sequential and reciprocal interactions between the oral
      epithelium and neural crest-derived mesenchyme. Recently, it has been reported
      that many factors such as Msx1, Pax9, Lef1, Bmp, Fgf, Wnt, Shh and Eda play a
      critical role in tooth development. It is expected that the further accumulation
      of evidence involved in mechanisms of tooth development and stem cell biology
      could lead to the development of tooth regenerative therapy based on this
      biological evidence.

PMID- 15995302
TI  - [Mechanisms of action in bisphosphonates].
AB  - Bisphosphonates have the high affinity to hydroxyapatites and act as the
      inhibition of bone resorption in a low dose, while they act as the inhibition of
      the calcification in a high dose. In tissues, bisphosphonates adsorbing bone
      surface become detached by a low pH environment with bone resorption and then act
      on osteoclasts. In cellular events, nitrogen-containing compounds interfere with
      protein prenylation by inhibiting an enzyme in the HMG-CoA reductase pathway. On
      the other hand, non-nitrogen-containing bisphosphonates act by producing toxic
      analogs of ATP that cause cell death.

PMID- 15995303
TI  - [The mechanism of parathyroid hormone action].
AB  - PTH is one of the promising bone forming agents. However, its mechanism for bone
      formation remains unknown. The putative accumulating hypothesis about the
      mechanism is the following;the involvement of local bone forming growth factors,
      such as insulin-like growth factor-I, anti-apoptotic actions through Runx2 and
      Smad3 etc, the transcriptional regulators, such as AP-1 and CREB. The research
      for the action of PTH would bring the development of effective PTH treatment and
      the investment of agents, which are more effective to increase bone formation.

PMID- 15995304
TI  - [Cell transplantation for periodontal diseases. A novel periodontal tissue
      regenerative therapy using bone marrow mesenchymal stem cells].
AB  - A major goal of periodontal therapy is to reconstruct healthy periodontium
      destroyed by periodontal diseases. Basic studies have revealed that
      transplantation of mesenchymal stem cells (MSC) into periodontal defects promotes
      regeneration of periodontal tissue. We have developed a novel method for
      periodontal therapy using MSC. Human bone marrow cells are obtained from the
      iliac crest and expanded in vitro at Cell and Tissue Engineering Center in
      Hiroshima University Hospital. MSC are, then, isolated and mixed with
      Atelocollagen at final concentrations of 2 x 10(7) cells/mL. These MSC in
      Atelocollagen are transplanted into periodontal osseous defects at the
      periodontal surgery. The results in all seven patients who received the own MSC
      transplantation have shown good clinical course. Further basic studies and the
      continuous clinical trial are needed to prove the effectiveness of the clinical
      application.

PMID- 15995305
TI  - [Pathogenesis and therapy for vascular calcification in patients on chronic
      hemodialysis].
AB  - Vascular calcification is a common complication of end-stage renal disease (ESRD)
      and is likely related to the high incidence of cardiovascular disease in patients
      with ESRD. Vascular calcification occurs both in the vascular intima and in the
      tunica media. Intimal calcification is disseminated and is associated with
      damaged endothelium and macrophage. On the contrary, medial calcification occurs
      in patchy distribution and the most frequent cells types found in its vicinity
      are smooth muscle cells (SMC). The uremic state is associated with numerous
      metabolic abnormalities and endocrine disturbances primarily involving calcium
      and phosphorus metabolism. In addition, ESRD is considered state of active
      inflammatory response. These dysfunctions likely contribute to the development
      and progression of vascular calcification. Recent reports have shown that this is
      a highly regulated process governed by factors that closely resemble calcium
      deposition in bone tissue. Vascular calcification requires changes in the
      phenotype of SMC and the expression of several bone-associated proteins normally
      involved in bone metabolism. This review is focused on the role of phosphorus in
      the pathogenesis of vascular calcification and the therapeutic approaches
      currently available to slow its progression in patients with ESRD.

PMID- 15995306
TI  - [Regulation of phosphate balance in the kidney].
AB  - The reabsorption of phosphate filtered at glomeruli is mediated by sodium
      dependent phosphate (Na/Pi) cotransporter families in the brush border membrane
      of the proximal tubuli. The type II a Na/Pi cotransporter plays the most
      important role for renal phosphate reabsorption and is regulated by several
      factors, e.g. parathyroid hormone (PTH) and fibroblastic growth factor-23. PTH
      induces endocytosis of the type II a Na/Pi cotransporter from the brush border
      membrane and subsequent lysosomal degradation, and the decrement of the type II a
      Na/Pi cotransporter in the brush border membrane leads the phosphate reabsorption
      inhibition.

PMID- 15995307
TI  - [Functional disorder of the parathyroid gland and vascular calcification in
      hemodialysis patients].
AB  - In uremia, hyperparathyroidism induces hypercalcemia and hyperphosphatemia.
      Relative hypoparathyroidism also causes hypercalcemia and hyperphosphatemia due
      to the low buffering capacity of the bone. Thus control of PTH within target
      range is very important.

PMID- 15995308
TI  - [The role of phosphatonin in phosphate metabolism].
AB  - PTH and active vitamin D are well known as classical phosphate regulating
      hormones. However, presence of some phosphaturic factors is assumed from
      investigations about TIO, XLH, ADHR. Those diseases cause hypophsophatemia,
      hyperphosphaturia, low vitamin D and rickets/ostepmalacia. FGF-23, which has been
      detected from TIO tumors, can induce hypophosphatemia by direct inhibition on
      phosphate reabsorption and by suppressing 1,25 (OH)(2)D(3) production through the
      inhibition of 25-hydroxyvitaminD 1alpha-hydroxylase, in the kidney. We have still
      other phosphatonin candidates such as MEPE, FRP4, etc. The role of these
      substances are not clear yet. Future investigations are required to clarify their
      roles in phosphate metabolism.

PMID- 15995309
TI  - [Bone mineral density and vascular calcification].
AB  - It is of interest that in the general population, low bone mass is associated
      with a higher mortality rate due to atherosclerotic cardiovascular disease. In
      addition, the degree of aortic calcification is closely related with a lower bone
      mineral density (BMD). These results suggest that a low BMD may predict increased
      arterial stiffness. In ESRD patients, advanced arterial stiffness and low BMD due
      to renal osteodystrophy are not uncommon. Moreover, the initiation and
      progression of arterial stiffness and bone loss are accelerated by the same
      factors such as hyperphosphatemia secondary to chronic renal failure. A lower BMD
      might be more clearly associated with a higher PWV in dialysis patients than in
      the general population. To prove this hypothesis, we performed a preliminary
      cross-sectional study to investigate the relationship between BMD, as determined
      by calcaneal osteo-sono index (OSI), and arterial stiffness, as measured by the
      brachial-ankle PWV (baPWV). Our study demonstrated that calcaneal OSI, a marker
      for estimated BMD, has a powerful predictor of arterial stiffness, independent of
      classic risk factors, malnutrition, or inflammation markers. The evaluation of
      BMD needs to grasp not only the status of bone disease, but also the degree of
      arterial stiffness.

PMID- 15995310
TI  - [Mechanism of arterial calcification with regards to atherosclerotic
      calcification and medial artery calcification].
AB  - Vascular calcification is a mechanism of active process, which includes
      inflammation and metabolism of bone formation. There are two different types of
      vascular calcification; atherosclerotic calcification and medial artery
      calcification. As seen in bone metabolism, vascular calcification is reported to
      be through enchondral ossification through BMP-2-Cbfa1 signal pathway, and
      through intramembranous ossification through BMP-2-Msx2 signal pathway. In the
      tissue of vascular calcification, several proteins which are related to bone and
      bone matrix metabolism have been shown to be present, such as bone morphogenic
      protein, osteoprotegerin, matrix gla protein, and osteopontin.

PMID- 15995311
TI  - [Diagnosis and Intervention for calcified coronary artery disease--role of multi
      slice CT].
AB  - Calcification has been well known to exist in atherosclerotic lesions from 19th
      century. The mechanisms of calcification are still unknown. Coronary stenoses can
      be treated by percutaneous coronary intervention using drug eluting stents at
      present. To the contrary, calcified coronary lesions are still difficult to be
      treated due to stent unexpansion despite of high pressure dilatation. Recent
      development of multi-slice CT (MDCT) has made it possible to diagnose coronary
      stenoses non-invasively. Coronary calcification is easily detected using MDCT,
      however, quantification of stenosis is difficult in calcified lesions.

PMID- 15995312
TI  - [Pharmacologic intervention for vascular calcification].
AB  - In patients with chronic renal insufficiency and dialysis, phosphate retention is
      a major factor in the development of vascular calcification. Prevention of
      phosphate retention with dietary and pharmacological means may prevent vascular
      calcification. Current therapy for hyperphosphatemia includes the administration
      of phosphate binders such as calcium carbonate (or calcium acetate), ammonium
      based compounds, and phosphate-binding polymers (Renagel; sevelamer
      hydrochloride). However, it is difficult to administrate present phosphate
      binders to patients because of hypocalcaemia, outright toxicity, and constipation
      as its side effect. It is needed to development new drugs having fewer side
      effects and better compliance.

PMID- 15995313
TI  - [Osteoporosis and smoking].
AB  - Smoking is one of the greatest risk factors for human health. Recent meta
      analyses on the effects of smoking on the bone revealed that current smokers
      sustained decreased bone mass and increased fracture risk at age 50 years and
      older. These relationships remained significant after adjustment for the effects
      of age, years since menopause and body weight regardless of sex. The effect of
      smoking on bone mass was observed consistently over the skeletal sites and that
      on fracture risk was seen all the skeletal sites except the forearm. Ex-smoker
      ran the intermediate risk between non-smoker and current smoker, which implies
      beneficial effect of quitting smoking. It has recently been indicated that
      intrauterine exposure to tobacco smoke retards skeletal growth resulting in
      increased risk for fracture later in life, which should be confirmed by further
      studies.

PMID- 15995314
TI  - [Jaws of predatory mammals].
AB  - Mammals are classified into the three types by chewing manner:predatory mammals,
      herbivorous mammals, and omnivorous mammals. The mechanism of mastication was
      correlate with the development and topography of muscles and depending on the
      arrangement of the teeth and mandibular joint. The predatory animals are
      characterised by the fact that the muscles which open and close the mouth are
      particularly powerful while those muscles responsible for grinding action are
      relatively poorly developed. And the shape of mandibular joint is restricted to
      the movement of mandible.

PMID- 15995322
TI  - Molecular classification and pathogenesis of eosinophilic disorders: 2005 update.
AB  - Use of the term "idiopathic hypereosinophilic syndrome (HES)" has highlighted our
      basic lack of understanding of the molecular pathophysiology of eosinophilic
      disorders. However, over the last 10 years, the study of hypereosinophilia has
      enjoyed a revival. This interest has been rekindled by two factors: (1) the
      development of increasingly sophisticated molecular biology techniques that have
      unmasked recurrent genetic abnormalities linked to eosinophilia, and (2) the
      successful application of targeted therapy with agents such as imatinib to treat
      eosinophilic diseases. To date, most of these recurrent molecular abnormalities
      have resulted in constitutively activated fusion tyrosine kinases whose
      phenotypic consequence is an eosinophilia-associated myeloid disorder. Most
      notable among these are rearrangements of platelet-derived growth factor
      receptors alpha and beta (PDGFRalpha, PDGFRbeta), which define a small subset of
      patients with eosinophilic chronic myeloproliferative disorders (MPDs) and/or
      overlap myelodysplastic syndrome/MPD syndromes, including chronic myelomonocytic
      leukemia. Discovery of the cryptic FIP1L1-PDGFRA gene fusion in cytogenetically
      normal patients with systemic mast cell disease with eosinophilia or idiopathic
      HES has redefined these diseases as clonal eosinophilias. A growing list of
      fibroblast growth factor receptor 1 fusion partners has similarly emerged in the
      8p11 myeloproliferative syndromes, which are often characterized by elevated
      eosinophil counts. Herein the focus is on the molecular gains made in these MPD
      type eosinophilias, and the classification and clinicopathological issues related
      to hypereosinophilic syndromes, including the lymphocyte variant. Success in
      establishing the molecular basis of a group of once seemingly heterogeneous
      diseases has now the laid the foundation for establishing a semi-molecular
      classification scheme of eosinophilic disorders.

PMID- 15995323
TI  - Interferon treatment for hypereosinophilic syndromes and systemic mastocytosis.
AB  - Hypereosinophilic syndromes (HES) and systemic mastocytosis (SMCD) are
      heterogeneous disorders with clinical symptoms from local and remote effects of
      excessive proliferation of eosinophils and mast cells, respectively. Interferon
      alpha (IFN-alpha), alone or in combination with other medications, can be a
      useful, and at times life-saving, treatment for patients with HES. Receptors for
      IFN-alpha are present on eosinophils, and clinical benefits are due to its effect
      on eosinophil proliferation, migration, activation, and survival. These effects
      are likely mediated through multiple pathways including, but not limited to,
      inhibition of eosinophil colony-forming cells, upregulation of IFN-gamma
      synthesis, and inhibition of production of eosinophil-active cytokines by T
      cells, mast cells, and mononuclear cells. IFN-alpha has been life-saving for
      patients with intractable HES that were resistant to prednisone, hydroxyurea, and
      other agents. Resistance to the eosinopenic effect of IFN-alpha does not develop
      and the dose of IFN-alpha necessary to maintain control of eosinophilia often
      decreases with time. The combination of IFN-alpha and hydroxyurea is very useful
      and allows dosage reduction of IFN-alpha and better control of hypereosinophilia
      than with either agent alone. The efficacy of IFN-alpha for treatment of SMCD has
      been more difficult to establish, with both favorable and unfavorable results
      reported. The disparate results may have resulted from the small number of
      patients with SMCD treated with IFN-alpha, the use of various criteria for a
      "successful" treatment outcome, short duration of treatment and follow-up, and
      the use of modest dosages. In reported series, side effects from IFN-alpha have
      frequently been dose-limiting. IFN-alpha improves many of the clinical symptoms
      of SMCD including dermatological, hematological, gastrointestinal, and systemic
      symptoms associated with histamine release. IFN-alpha has a beneficial effect on
      skeletal symptoms because of its ability to increase bone density and reduce
      painful episodes from vertebral fractures. No consistent improvement in bone
      marrow infiltration by mast cells has been demonstrated except in a recent study
      employing high dosages of IFN-alpha. A beneficial effect from the combination of
      IFN-alpha and prednisone has been reported for several patients, suggesting that
      combined use of these two medications may provide synergism in treatment
      outcomes.

PMID- 15995324
TI  - Systemic mastocytosis: bone marrow pathology, classification, and current
      therapies.
AB  - Mast cell disease (MCD) is characterized by the abnormal growth and accumulation
      of neoplastic mast cells (MC) in one or more organs. The diagnosis of systemic
      MCD is most commonly established by a thorough histological and
      immunohistochemical examination of a bone marrow (BM) trephine specimen. In cases
      with pathognomonic perivascular and -trabecular aggregates of morphologically
      atypical MC and significant BM involvement, the diagnosis may be relatively
      straightforward. In contrast, when a sparse, loose pattern of MC infiltration
      predominates, or when MCs are obscured by an associated non-MC hematological
      neoplasm, a high index of suspicion and use of adjunctive tests, including
      special stains, such as tryptase and CD25, may be necessary to reach a diagnosis.
      The updated classification for MCD clarifies the clinical and pathological
      criteria for categorizing patients into relatively discrete subgroups. Some
      cases, however, such those with Fip1-like-1-platelet-derived growth factor
      receptor alpha (FIP1L1-PDGFRA)(+) clonal eosinophilia associated with elevated
      serum tryptase levels, with features that overlap MCD and chronic eosinophilic
      leukemia, may not be easy to categorize on the basis of this classification.
      There is no standard therapy for MCD and treatment has to be tailored to the
      needs of the individual patient. MC-cytoreductive therapies, such as interferon
      alpha and chemotherapy, are generally reserved for patients with progressive
      disease and organopathy. A subset of MCD patients with associated eosinophilia
      who carry the FIP1L1-PDGFRA oncogene will achieve complete clinical,
      histological, and molecular remissions with imatinib mesylate therapy, in
      contrast to those with c-kit D816V mutations. The BM pathology, consensus
      classification, and current therapies for MCD are further discussed in this
      article.

PMID- 15995325
TI  - Modern diagnosis and treatment of primary eosinophilia.
AB  - The recent discovery of an eosinophilia-specific, imatinib-sensitive,
      karyotypically occult but fluorescence in situ hybridization-apparent molecular
      lesion in a subset of patients with blood eosinophilia has transformed the
      diagnostic as well as treatment approach to eosinophilic disorders. Primary (i.e.
      nonreactive) eosinophilia is considered either "clonal" or "idiopathic" based on
      the presence or absence, respectively, of either a molecular or bone marrow
      histological evidence for a myeloid neoplasm. Clonal eosinophilia might accompany
      a spectrum of clinicopathological entities, the minority of whom are molecularly
      characterized; Fip1-like-1-platelet-derived growth factor receptor alpha (FIP1L1
      PDGFRA(+)) systemic mastocytosis, platelet-derived growth factor receptor beta
      (PDGFRB)-rearranged atypical myeloproliferative disorder, chronic myeloid
      leukemia, and the 8p11 syndrome that is associated with fibroblast growth factor
      receptor 1 (FGFR1) rearrangement. Hypereosinophilic syndrome (HES) is a
      subcategory of idiopathic eosinophilia and is characterized by an absolute
      eosinophil count of > or =1.5 x 10(9)/l for at least 6 months as well as
      eosinophil-mediated tissue damage. At present, a working diagnosis of primary
      eosinophilia mandates a bone marrow examination, karyotype analysis, and
      additional molecular studies in order to provide the patient with accurate
      prognostic information as well as select appropriate therapy. For example, the
      presence of either PDGFRA or PDGFRB mutations warrants the use of imatinib in
      clonal eosinophilia. In HES, prednisone, hydroxyurea, and interferon-alpha
      constitute first-line therapy, whereas imatinib, cladribine, and monoclonal
      antibodies to either interleukin-5 (mepolizumab) or CD52 (alemtuzumab) are
      considered investigational. Allogeneic transplantation offers a viable treatment
      option for drug-refractory cases.

PMID- 15995326
TI  - Clonality and molecular pathogenesis of mastocytosis.
AB  - Mast cell is a hematopoietic lineage dependent on Kit signaling for growth,
      differentiation, and survival. Mast cells are found in excessive numbers in
      tissues in a heterogeneous group of disorders collectively known as mastocytosis.
      Last decade has witnessed important advancements in our understanding of the
      molecular pathology of mastocytosis. First, systemic mastocytosis has been found
      to be associated with activating codon 816 mutations of the c-kit gene. Second,
      this mutation was used as a tracking marker to elucidate the clonal nature of
      mastocytosis. These findings have resulted in consideration of systemic
      mastocytosis as a clonal neoplastic disorder of a hematopoietic progenitor cell.
      Improved knowledge of the mechanisms causing pathological mast cell growth will
      lead to the discovery of novel treatment options including drugs targeting the
      mutated Kit protein.

PMID- 15995327
TI  - Does cerebral perfusion improve following CSF diversion in pediatric
      hydrocephalus? A prospective study using 99mTc ECD single photon emission
      computed tomography.
AB  - AIMS AND OBJECTIVES: To study regional cerebral perfusion before and after
      ventriculoperitoneal shunt placement in children with hydrocephalus, using
      (99m)Tc ECD single photon emission computed tomography (SPECT). MATERIALS AND
      METHODS: 17 consecutive children (less than 16 years) with hydrocephalus due to
      various causes, who were planned for ventriculoperitoneal shunt, were included in
      this prospective study. Brain SPECT using (99m)Tc ECD was performed pre- and
      postoperatively and changes in cerebral perfusion were compared with the change
      in ventricular size (assessed using Evan's ratio). OBSERVATIONS: There were 11
      males and 6 females with a median age of 24 months. Nine children were up to 2
      years of age and the mean duration of symptoms was 6 months. The cause of
      hydrocephalus was congenital in 10, secondary to tumor in 5 and as sequelae of
      infection in 2 children. Fourteen children (82%) showed improvement in cerebral
      perfusion following shunting. Of these, 12 also had a concomitant decrease in
      ventricular size postoperatively. RESULTS: On logistic regression analysis, none
      of the factors analyzed, i.e. age, duration of symptoms, etiology of
      hydrocephalus and decrease in ventricular size, were found to predict improvement
      of cerebral perfusion following shunting. CONCLUSIONS: Cerebral perfusion
      improves in the majority of the children following CSF diversionary procedures,
      and contrary to the common belief, duration of hydrocephalus and decreased
      ventricular size do not influence this improvement in cerebral perfusion. SPECT
      can therefore prove to be a valuable tool for objective assessment of improvement
      in cerebral perfusion in children with hydrocephalus secondary to various
      etiologies following surgical or medical interventions.

PMID- 15995328
TI  - Assessment of childhood intracranial pressure recordings using a new method of
      processing intracranial pressure signals.
AB  - BACKGROUND: Intracranial compliance may be more reliably predicted by the
      pulsatile component (pulse pressure) than the steady (mean pressure) component of
      intracranial pressure (ICP). A new method of processing continuous ICP signals
      assessing both components of ICP is described and applied to the ICP recordings
      of 6 pediatric cases. METHOD: The new method was applied to each subsequent 6
      second time sequence window of a continuous ICP signal. For time sequence windows
      including single ICP waves, the following time sequence (TS.x)-related parameters
      were computed: (a) mean ICP (i.e. TS.MeanP) was computed according to the
      currently used and known technology; (b) the mean ICP wave was computed according
      to the new method, characterized by mean wave amplitude (i.e. TS.MeanWavedP) and
      mean wave latency (i.e. TS.MeanWavedT). Cases No. 1-4 were treated for
      hydrocephalus and cases No. 5 and 6 for craniosynostosis. RESULTS: In 5 children,
      clinical intracranial hypertension was associated with elevations of mean ICP
      above 15-20 mm Hg of variable durations. The ICP recordings of the 5 children
      with intracranial hypertension and successful outcome after surgery revealed mean
      wave amplitude values above 5 mm Hg. Mean wave latency was more variable, ranging
      between 0.10 and 0.25 s. CONCLUSIONS: In the children with intracranial
      hypertension and successful outcome after surgery, mean wave amplitude was
      variably above 5 mm Hg. It is suggested that mean wave amplitude may be a useful
      parameter by more directly predicting cerebral compliance than mean ICP.

PMID- 15995329
TI  - Cerebrospinal fluid shunt infections in children.
AB  - Infections of cerebrospinal fluid shunts continue to be a substantial source of
      mortality and morbidity in children with hydrocephalus. Although several
      therapeutic modalities are currently used for the treatment of shunt infections,
      there are no clear guidelines for treatment. The purpose of this study was to
      determine the common pathogens of cerebrospinal fluid shunt infections and
      evaluate the success of our management. Thirty-five children treated for
      ventriculoperitoneal shunt infections over the past 9 years were reviewed. The
      management protocol consisted of the removal of the infected shunt, the
      application of ventricular taps or reservoir placement, intraventricular
      antibiotic treatment, and the placement of a new shunt when cerebrospinal fluid
      sterility was achieved. Four patients were treated with antibiotics alone. Most
      episodes occurred within 4 months of shunt placement. The most common causative
      microorganism identified was Staphylococcus epidermidis, followed by S. aureus,
      and S. warneri. Three patients died from complications of shunt infections, 2
      patients had a recurrent shunt infection, while the remaining 29 patients
      remained free from shunt-related complications. In agreement with the evidence
      published in the literature, our findings suggest that the above management
      protocol is effective for the treatment of cerebrospinal fluid shunt infections.

PMID- 15995330
TI  - The early years of hemispherectomy.
AB  - Today, hemispherectomy is a well-established procedure for the treatment of some
      sorts of catastrophic epilepsies. This, however, has not always been the case.
      The technique was developed to deal with brain tumors; however, the initial
      results were not remarkable. Moreover, when its morbidity became evident, it was
      almost abandoned. Had it not been for a shift in its use, with a huge increase in
      operations on patients with infantile hemiplegia, this surgery would certainly
      have disappeared. This paper focuses on the facts that surrounded these early
      years.

PMID- 15995331
TI  - Traumatic vertebral artery dissection in a child with brachial plexus injury.
AB  - Traumatic vertebral artery dissection is an unusual event in children, but early
      recognition and treatment are important to prevent neurological deficits. The
      authors present a case of a 4-year-old boy with a traumatic extracranial
      vertebral artery dissection, who suffers from left arm monoplegia due to brachial
      plexus injury.

PMID- 15995332
TI  - Penetrating intracranial stone.
AB  - Traumatic intracranial foreign objects may cause cranial hemorrhage and contusion
      at an early stage and epileptic seizures and infections at a later stage, leading
      to morbidity and mortality in children. In the present study we report a case of
      a traumatic intracranial stone, which is a rarely encountered foreign object in
      intracranial traumatic injuries.

PMID- 15995333
TI  - Spontaneous movement of bullets in the interhemispheric region.
AB  - Gunshot wounds to the head are usually mortal injuries. Their frequency has been
      increasing in the last years because of increasing crime and war rates.
      Penetrating craniocerebral injury in children and adolescents at the age of 17 or
      under is an increasing cause of emergent neurosurgical admissions to major
      metropolitan medical centers. I report a patient in whom a bullet in the brain
      moved from the interhemispheric region to 1 cm to the left of the inner occipital
      protuberance and midline. The patient recovered from surgery uneventfully. He was
      followed up for 4 years without neurodeficits. Spontaneous movement of bullets
      within the brain has been reported sporadically. The removal of intracerebral
      bullets is obviously warranted in patients undergoing craniotomy or craniectomy
      for debridement or evacuation of intracerebral clots or bone fragments if the
      metallic fragment is in proximity to the operative site. Before surgical removal
      of any intracerebral bullet, it is recommended that an intraoperative plain skull
      X-ray be obtained after final positioning of the head.

PMID- 15995334
TI  - Bifrontal decompressive craniotomy in a 6-month-old infant with posttraumatic
      refractory intracranial hypertension.
AB  - OBJECTIVE: To document the outcome of bifrontal decompressive craniotomy (BDC) in
      an infant who developed refractory intracranial hypertension (IH) and massive
      brain infarction following severe head injury. CLINICAL PRESENTATION: A 6-month
      old girl sustained a severe closed head injury in a car accident. Her Glasgow
      coma score dropped from 10 to 6/15 within 6 h after admission, and her pupils
      became dilated and fixed. CT brain scans showed severe brain swelling and
      extensive infarction in both cerebral hemispheres with no grey-white mater
      differentiation. She developed a state of refractory IH despite maximal medical
      treatment. INTERVENTION: She had BDC and duraplasty carried out 8 h after
      admission. She made a quick recovery to Glasgow outcome score 3, and her total
      hospital stay was 10 weeks. CONCLUSION: BDC can be a life-saving procedure for
      infants with refractory IH and massive brain infarction.

PMID- 15995335
TI  - Spinal epidural epitheloid hemangioma--case report and review of the literature.
AB  - Epitheloid hemangiomas are benign vascular lesions composed of epitheloid
      endothelial-cell-lined channels. We report an unusual case of a purely extradural
      non-osseous spinal epitheloid hemangioma presenting with quadriparesis. A 5-year
      old boy presented with neck pain and quadriparesis following a trivial fall. MRI
      revealed a mixed intensity extradural lesion compressing the cervico-thoracic
      spinal cord posteriorly. At surgery the lesion consisted of vascular granulation
      tissue admixed with blood clots without abnormal vessels. Bone was normal.
      Histopathology revealed it to be an epitheloid hemangioma. The case and relevant
      literature is reviewed.

PMID- 15995336
TI  - Teratoma in human tail lipoma.
AB  - We report a case of a rare congenital teratoma that developed in a lipoma
      attached to a remnant human tail. A male newborn baby presented with a large, 3
      cm mass with an open margin, which pedunculated from a tail attached to the
      midline skin of the coccygeal area. Magnetic resonance images demonstrated
      multiple sacral spinal bifida without cord tethering, and also showed neural
      roots and a lipoma and teratoma with peripheral homogeneous high density and
      internal low density on T(2)-weighted images. Intraoperatively, we found and
      dissected two nerve roots from the filum terminale which extended into the mass.
      Pathologic examination of the mass revealed abnormal differentiation of
      respiratory epithelium and squamous cell metaplasia along the open margin of the
      mass, and mainly lipoma in the rest of the mass. We suggest that this case could
      support the hypothesis of transient teratomatous cells in the pathogenesis of the
      spina bifida with lumbosacral lipoma.

PMID- 15995337
TI  - Ulnar nerve abscess and relapse in a patient with indeterminate leprosy 1 year
      after completion of multidrug therapy.
AB  - The introduction of multidrug therapy has efficiently controlled leprosy in
      developing countries. However, Mycobacterium laprae may survive and cause relapse
      despite adequate treatment with antileprosy drugs. Relapse may be characterized
      by a combination of new signs or symptoms and presence of acid-fast bacilli on
      skin or nerve biopsy samples. We report a case of a child in whom ulnar abscess
      developed 12 months after successful completion of multidrug therapy with
      clinical and histopathological evidence of relapse.

PMID- 15995338
TI  - Endoscopic third ventriculostomy through the interfornicial space.
AB  - Endoscopic third ventriculostomy (ETV) is the most common cranial endoscopic
      surgery being done worldwide for a variety of conditions resulting in
      hydrocephalus. We report ETV in a case of congenital hydrocephalus with deficient
      third ventricular roof and wide interfornicial space. A 6-month-old male child
      presented with gradual progressive head enlargement and signs of raised
      intracranial pressure. Computed tomography of the head showed aqueductal stenosis
      with enlargement of third and lateral ventricles. The patient was operated under
      general anesthesia with endotracheal intubation. A right coronal burr hole and
      free-hand entry were made into the right lateral ventricle. The anterior part of
      the septum and the third ventricular roof were deficient with a narrow Monro's
      foramen and the third ventricular floor was visible through the space between
      both fornices. ETV was done in standard fashion. Postoperatively the patient
      showed uneventful recovery clinicoradiologically. We review the literature and
      discuss the findings and technique of ETV in this rare entity.

PMID- 15995339
TI  - Reduplication of ventriculoperitoneal shunt catheter tip back through shunt
      tract.

PMID- 15995340
TI  - Vertex epidural hematoma.

PMID- 15995341
TI  - Expression of mediators of renal injury in the remnant kidney of ROP mice is
      attenuated by cyclooxygenase-2 inhibition.
AB  - To investigate the effects of cyclooxygenase-2 (COX-2) inhibition on renal injury
      of mice, ROP mice were subjected to subtotal ablation ('remnant'). A subset of
      the remnant group was treated with a selective COX-2 inhibitor, SC58236, in the
      drinking water. At 12 weeks the remnant group developed significant albuminuria
      (181.3 +/- 15.8 microg/24 h), which was blunted by SC58236 treatment (138.9 +/-
      17.1; p < 0.05 compared to remnant). SC58236 did not alter systemic blood
      pressure or GFR significantly. Immunoreactive COX-2 was upregulated in remnant
      (1.88 +/- 0.35 fold sham, n = 8, p < 0.05), which was blunted by SC58236 (to 1.26
      +/- 0.31 fold sham). Collagen IV mRNA increased significantly in remnant kidneys
      (2.69 +/- 0.34 fold sham, n = 8, p < 0.05), and this increase was inhibited by
      SC58236 treatment (to 1.84 +/- 0.32 fold control). Immunoreactive TGF-beta1,
      connective tissue growth factor, HGF receptor, c-Met, and fibronectin all
      increased in remnant (2.85 +/- 0.51, 3.83 +/- 0.55, 2.56 +/- 0.31, and 2.80 +/-
      0.39 fold sham respectively, n = 4-8, p < 0.05), and SC58236 blunted the
      increases (to 1.45 +/- 0.34, 1.85 +/- 0.13, 1.75 +/- 0.30, and 1.60 +/- 0.32 fold
      sham). Immunohistochemistry indicated that the major localization for these
      progression factors was in the tubulointerstitium, especially in the scar area,
      which is in agreement with the expression of a macrophage marker, F4/80.
      Therefore, these results indicate that in a mouse model of subtotal renal
      ablation, COX-2 inhibition blocks expression of mediators of renal
      tubulointerstitial injury.

PMID- 15995342
TI  - Antagonistic and agonistic GnRH analogue treatment of precocious puberty:
      tracking gonadotropin concentrations in urine.
AB  - BACKGROUND: The pharmacodynamics of gonadotropin-releasing hormone (GnRH)
      agonists includes an initial 'flare-up' of the pituitary-gonadal axis, followed
      by reduced luteinizing hormone (LH) secretion. The question is if combining a
      short-acting antagonist with a long-acting agonist can diminish gonadotropin
      flare-up. METHODS: To achieve quick downregulation in patients with recently
      diagnosed central precocious puberty (CPP, 7 patients) or short stature with
      short predicted final height (3 patients), we combined the GnRH antagonist
      cetrorelix (3 subcutaneous injections every 72 h) at the beginning of GnRH
      agonist treatment (leuprorelin or triptorelin) in 6 patients and compared the
      effect to 4 patients treated solely with GnRH agonist. To monitor effects, we
      measured LH and FSH concentrations in urine collected from initial morning
      urination during the first month of treatment. RESULTS: In both treatment groups,
      gonadotropin flare-up could be detected in urine levels increased due to the
      flare-up phenomenon which was of short duration (<5 days) in the majority (5 of
      6) of combined-treated patients and in the minority (1 of 4) of patients treated
      by agonist alone. During the first 10 days of treatment, mean LH concentration
      measured in urine was significantly lower in 4 CPP patients treated by the
      combined therapy compared to 3 CPP patients treated by the agonist only (mean LH
      combined therapy: 10.4 +/- 2.8 vs. 20.1 +/- 11.0 mU/ml in the agonist-only group,
      mean +/- SEM, p < 0.05). Significant correlations between stimulated serum LH in
      GnRH test prior to treatment and maximum urine LH after initiating GnRH analogue
      treatment (r = 0.547, p = 0.043), as well as basal serum LH and basal urine LH (r
      = 0.685, p = 0.014) were found. CONCLUSION: Combined GnRH agonist and antagonist
      treatment led to rapid gonadotropin suppression. Also, urine measurements of LH
      and FSH seemed suitable for monitoring gonadotropin-inhibiting or -stimulating
      properties of GnRH analogues in individual patients. However, a controlled trial
      of a larger patient cohort is required to decide which treatment is the most
      effective.

PMID- 15995343
TI  - Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome.
AB  - BACKGROUND: Endocrine abnormalities, including hypocalcemia, thyroid dysfunction,
      and short stature, are associated with chromosome 22q11.2 microdeletion syndrome.
      This study was undertaken to examine the frequencies and clinical features of
      endocrine abnormalities in patients with 22q11.2 microdeletion syndrome. METHODS:
      We analyzed 61 patients with 22q11.2 microdeletion syndrome diagnosed based on
      the verification of microdeletion by fluorescent in situ hybridization (FISH)
      using a probe of the DiGeorge syndrome critical region (TUPLE1) at 22q11.2 and a
      control probe, ARSA at 22q13. Serum total calcium, phosphorus, and intact
      parathyroid hormone (PTH) levels were measured, thyroid function test was
      performed, and serum IGF-1 and IGFBP-3 levels were also estimated. Height and
      weight of patients were compared with individual chronological ages. RESULTS:
      Hypocalcemia was found in 20 patients (32.8%), and overt hypoparathyroidism in 8
      (13.1%). Two patients (3.3%) showed autoimmune thyroid diseases, 1 each with
      Graves' disease and Hashimoto thyroiditis. Ten patients (16.4%) were below the
      third percentile in height, but the serum IGF-1 level was normal in 9 out of
      these 10 patients. CONCLUSION: Our findings show that patients with chromosome
      22q11.2 microdeletion syndrome present with variable endocrine manifestations and
      variable clinical phenotypes. In addition to FISH analysis, careful endocrine
      evaluations are required in patients with this microdeletion syndrome,
      particularly for those with hypoparathyroidism or thyroid dysfunction.

PMID- 15995344
TI  - Synchronous endometrial and cervical tumors in a 26-year-old nullipara:
      diagnostic modalities updated.
AB  - Proton magnetic resonance spectroscopy (MRS), performed on conventional magnetic
      resonance imaging (MRI) scanners, provides useful information at the biochemical
      level. MRS has been used to measure tissue concentrations of proton-containing
      compounds such as organic and amino acids, and sugars in living tissues. We have
      used MRS in a 26-year-old female with suspected cervical and endometrial
      carcinomas. With the use of the above mentioned technique, biochemical
      differences in the endometrium and the cervix tissues were detected. The
      presented case is the first virgin patient in the relevant literature in whom
      endometrial and cervical carcinoma was detected. Choline (Cho), creatine (Cr), N
      acetylaspartate (NAA), lipid and lactate region of the MRS spectrum suggested
      that the technique could be used as an indicator of metabolic alterations in the
      cervical and endometrial tumor cells.

PMID- 15995345
TI  - The pleiotropy of telomerase against cell death.
AB  - The end of eukaryotic genomic DNA is capped by a specialized structure called as
      "telomere", which consists of the repetitive array of nucleotide sequence,
      TTAGGG, in humans and mice, and a variety of binding proteins. Telomerase is a
      ribonucleoprotein (RNP) complex responsible for the elongation of telomeres to
      maintain the genomic integrity, and is composed of telomerase reverse
      transcriptase (TERT), telomerase RNA component (TERC), and their associated
      factors regulating the catalytic activity of telomerase. Although it is now
      apparent that telomerase protects cells from apoptosis via the maintenance of
      genomic integrity by stabilizing telomeres, our understanding for the
      physiological role of telomerase is yet far from completion, and emerging
      evidence suggests that telomerase has additional extratelomeric roles in
      mediating cell survival and anti-apoptotic functions against various cytotoxic
      stresses. Here we summarize and discuss how telomerase and telomeres are involved
      in mediating cellular protection against apoptosis.

PMID- 15995347
TI  - Characterization of Ty3-gypsy-like elements in Hibiscus syriacus.
AB  - Southern blot analysis revealed a ubiquitous distribu-tion and high copy number
      of Ty3-gypsy-like elements in the genome of Hibiscus syriacus. Comparative
      phylogenetic analysis of the large subunit of Rubisco and the integrase region of
      Ty3-gypsy elements in various plant species indicated that the retrotransposon
      like sequences have different evolutionary histories and their own unique
      polymorphism in the H. syriacus population. Sequence-tagged site-restriction
      fragment length polymorphisms (STS-RFLP) analysis also indicated great
      variability in the numbers and sequences of Ty3-gypsy-like elements within H.
      syriacus varieties. Ty3-gypsy-like elements may still be active within H.
      syriacus, since Northern analysis of wounded leaves of H. syriacus variety Saehan
      with a probe for the integrase domain gave strong hybridization signals. The
      sequence heterogeneity and ubiquity of the Ty3-gypsy-like elements in H. syriacus
      genomes could provide reliable DNA markers for line identification as well for
      the analysis of genetic diversity in H. syriacus.

PMID- 15995346
TI  - Isolation of Xenopus FGF-8b and comparison with FGF-8a.
AB  - The Xenopus FGF-8a and FGF-8b isoforms have been reported to be neural crest and
      neuronal inducers, respectively. However, cloning of Xenopus FGF-8b (XFGF-8b) has
      not been reported previously and the two isoforms do not seem to have been
      clearly distinguished in Xenopus experiments. Here, we describe the cloning and
      expression of XFGF-8b and compare the effects of the two isoforms. XFGF-8b has an
      11 amino acid insert in its N-terminal region compared with XFGF-8a. Both
      isoforms are expressed in the anterior neural regions of the early embryo, and in
      the apical ectodermal ridge of limb buds and tips of growing digits in the larval
      stages. However, XFGF-8b is more abundant than XFGF-8a throughout early
      development. The two isoforms are also regulated in similar fashion by retinoic
      acid in early development. However, although both XFGF-8a and XFGF-8b induce
      ectopic neurogenesis, only XFGF-8a appears to be involved in neural crest
      induction.

PMID- 15995348
TI  - Biochemical analysis of a cytosolic small heat shock protein, NtHSP18.3, from
      Nicotiana tabacum.
AB  - Small heat shock proteins (sHSPs) are widely distributed, and their function and
      diversity of structure have been much studied in the field of molecular
      chaperones. In plants, which frequently have to cope with hostile environments,
      sHSPs are much more abundant and diverse than in other forms of life. In response
      to high temperature stress, sHSPs of more than twenty kinds can make up more than
      1% of soluble plant proteins. We isolated a genomic clone, NtHSP18.3, from
      Nicotiana tabacum that encodes the complete open reading frame of a cytosolic
      class I small heat shock protein. To investigate the function of NtHSP18.3 in
      vitro, it was overproduced in Escherichia coli and purified. The purified
      NtHSP18.3 had typical molecular chaperone activity as it protected citrate
      synthase and luciferase from high temperature-induced aggregation. When E. coli
      celluar proteins were incubated with NtHSP18.3, a large proportion of the
      proteins remained soluble at temperatures as high as 70 degrees . Native gel
      analysis suggested that NtHSP18.3 is a dodecameric oligomer as the form present
      and showing molecular chaperone activity at the condition tested. Binding of bis
      ANS to the oligomers of NtHSP18.3 indicated that exposure of their hydrophobic
      surfaces increased as the temperature was raised. Taken together, our data
      suggested that NtHSP18.3 is a molecular chaperone that functions as a dodecameric
      complex and possibly in a temperature-induced manner.

PMID- 15995349
TI  - A basic helix-loop-helix transcription factor regulates cell elongation and seed
      germination.
AB  - Plants are sessile and rely on a wide variety of growth hormones to adjust growth
      and development in response to internal and external stimuli. We have identified
      a gene, designated NAN, encoding a basic helix-loop-helix (bHLH) transcription
      factor that regulates cell elongation and seed germination in plants. NAN has an
      HLH motif in its C-terminal region but does not have any other discernible
      homologies to bHLH proteins. A bipartite nuclear localization signal is located
      close to the HLH motif. An Arabidopsis mutant, nan-1D, in which NAN is activated
      by the insertion of the 35S enhancer, exhibits growth retardation with short
      hypocotyls and curled leaves. It is also characterized by reduced seed
      germination and apical hook formation, symptomatic of GA deficiency or disrupted
      GA signaling. The phenotypic effects of nan-1D were increased by treatment with
      paclobutrazol (PAC), an inhibitor of gibberellic acid (GA) biosynthesis. NAN is
      constitutively expressed throughout the life cycle. Our observations indicate
      that NAN has a housekeeping role in plant growth and development, particularly in
      seed germination and cell elongation, and that it may modulate GA signaling.

PMID- 15995350
TI  - Characterization of an Arabidopsis gene that mediates cytokinin signaling in
      shoot apical meristem development.
AB  - Cytokinins are adenine derivatives that regulate numerous plant growth and
      developmental processes, including apical and floral meristem development, stem
      growth, leaf senescence, apical dominance, and stress tolerance. However, not
      much is known about how cytokinin biosynthesis and metabolism is regulated. We
      identified a novel Arabidopsis gene, ALL, encoding an aldolase-like enzyme that
      regulates cytokinin signaling. An Arabidopsis mutant, all-1D, in which ALL is
      activated by the nearby insertion of the 35S enhancer, exhibited extreme dwarfism
      with rolled, dark-green leaves and reduced apical dominance, symptomatic of
      cytokinin-overproducing mutants. Consistent with this, ARR4 and ARR5, two
      representative primary cytokinin-responsive genes, were significantly induced in
      all-1D. Whereas SHOOT MERISTEMLESS (STM) and KNAT1, which regulate meristem
      development, were also greatly induced, expression of REV and PHV that regulate
      lateral organ polarity was inhibited. ALL encodes an aldolase-like enzyme that
      belongs to the HpcH/HpaI aldolase family in prokaryotes and is down-regulated by
      exogenous cytokinin, possibly through a negative feedback pathway. We propose
      that ALL is involved in cytokinin biosynthesis or metabolism and acts as a
      positive regulator of cytokinin signaling during shoot apical meristem
      development and determination of lateral organ polarity.

PMID- 15995351
TI  - P-Selectin-mediated acute inflammation can be blocked by chemically modified
      heparin, RO-heparin.
AB  - Selectins are carbohydrate-binding cell adhesion molecules that play a major role
      in the initiation of inflammatory responses. Heparin can bind to P-selectin, and
      its anti-inflammatory property is mainly due to inhibition of P-selectin.
      However, the strong anticoagulant activity of heparin limits its clinical use. We
      prepared periodate-oxidized, borohydride-reduced heparin (RO-heparin) by chemical
      modification and tested its anticoagulant and anti-inflammatory activities.
      Activated partial thromboplastin time (aPTT) assays showed that, compared with
      heparin, RO-heparin had greatly reduced anticoagulant activity. Intravenous
      administration of this compound led to reduction in the peritoneal infiltration
      of neutrophils in a mouse acute inflammation model. In vitro cell adhesion
      experiments demonstrated that the effect of RO-heparin on inflammatory responses
      was mainly due to inhibiting the interaction of P-selectin with its ligands.
      These results indicate that RO-heparin may be a safer treatment for inflammation
      than heparin, especially when selectin is targeted.

PMID- 15995352
TI  - The effect of ethanol on the physical properties of neuronal membranes.
AB  - Intramolecular excimer formation of 1,3-di(1-pyrenyl) propane(Py-3-Py) and
      fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) were used to
      evaluate the effect of ethanol on the rate and range of lateral and rotational
      mobilities of bulk bilayer structures of synaptosomal plasma membrane vesicles
      (SPMVs) from the bovine cerebral cortex. Ethanol increased the excimer to monomer
      fluorescence intensity ratio (I'/I) of Py-3-Py in the SPMVs. Selective quenching
      of both DPH and Py-3-Py by trinitrophenyl groups was used to examine the range of
      transbilayer asymmetric rotational mobility and the rate and range of
      transbilayer asymmetric lateral mobility of SPMVs. Ethanol increased the
      rotational and lateral mobility of the outer monolayer more than of the inner
      one. Thus ethanol has a selective fluidizing effect within the transbilayer
      domains of the SPMVs. Radiationless energy transfer from the tryptophans of
      membrane proteins to Py-3-Py was used to examine both the effect of ethanol on
      annular lipid fluidity and protein distribution in the SPMVs. Ethanol increased
      annular lipid fluidity and also caused membrane proteins to cluster. These
      effects on neuronal membranes may be responsible for some, though not all, of the
      general anesthetic actions of ethanol.

PMID- 15995353
TI  - Identification of essential genes in Streptococcus pneumoniae by allelic
      replacement mutagenesis.
AB  - To find potential targets of novel antimicrobial agents, we identified essential
      genes of Streptococcus pneumoniae using comparative genomics and allelic
      replacement mutagenesis. We compared the genome of S. pneumoniae R6 with those of
      Bacillus subtilis, Enterococcus faecalis, Escherichia coli, and Staphylococcus
      aureus, and selected 693 candidate target genes with > 40% amino acid sequence
      identity to the corresponding genes in at least two of the other species. The 693
      genes were disrupted and 133 were found to be essential for growth. Of these, 32
      encoded proteins of unknown function, and we were able to identify orthologues of
      22 of these genes by genomic comparisons. The experimental method used in this
      study is easy to perform, rapid and efficient for identifying essential genes of
      bacterial pathogens.

PMID- 15995354
TI  - Phospholipase C-beta3 mediates the thrombin-induced Ca2+ response in glial cells.
AB  - Phospholipase C-beta (PLC-beta) hydrolyses phosphatidylinositol 4,5-bisphosphate
      and generates inositol 1,4,5-trisphosphate in response to activation of various G
      protein-coupled receptors (GPCRs). Using glial cells from knock-out mice lacking
      either PLC-beta1 [PLC-beta1 (-/-)] or PLC-beta3 [PLC-beta3 (-/-)], we examined
      which isotype of PLC-beta participated in the cellular signaling events triggered
      by thrombin. Generation of inositol phosphates (IPs) was enhanced by thrombin in
      PLC-beta1 (-/-) cells, but was negligible in PLC-beta3 (-/-) cells. Expression of
      PLC-beta3 in PLC-beta3 (-/-) cells resulted in an increase in pertussis toxin
      (PTx)-sensitive IPs in response to thrombin as well as to PAR1-specific peptide,
      while expression of PLC-beta1 in PLC-beta1 (-/-) cells did not have any effect on
      IP generation. The thrombin-induced [Ca2+]i increase was delayed and attenuated
      in PLC-beta3 (-/-) cells, but normal in PLC-beta1 (-/-) cells. Pertussis toxin
      evoked a delayed [Ca2+]i increase in PLC-beta3 (-/-) cells as well as in PLC
      beta1 (-/-) cells. These results suggest that activation of PLC-beta3 by
      pertussis toxin-sensitive G proteins is responsible for the transient [Ca2+]i
      increase in response to thrombin, whereas the delayed [Ca2+]i increase may be due
      to activation of some other PLC, such as PLC-beta4, acting via PTx-insensitive G
      proteins.

PMID- 15995355
TI  - Alterations in the localization of calbindin D28K-, calretinin-, and parvalbumin
      immunoreactive neurons of rabbit retinal ganglion cell layer from ischemia and
      reperfusion.
AB  - Calcium-binding proteins are thought to play important roles in calcium
      buffering. The present study investigated the effects of ischemia and reperfusion
      on calbindin D28K, calretinin, and parvalbumin immunoreactivity in the ganglion
      cell layer of the rabbit. Rabbits were administered ischemic damage by increasing
      the intraocular pressure. After 60 and 90 min of ischemia, reperfusion (7 d) was
      allowed to occur. The b-wave of the electroretinogram (ERG) was reduced by more
      than 50% and almost 80% in retina given ischemia for 60 and 90 min, respectively.
      The oscillatory potential (OPs) wave was reduced approximately 50% at 60 min
      ischemia and 70% at 90 min ischemia. In both normal and ischemic-treated retina,
      calcium-binding protein immunoreactivity was seen in many cells in the ganglion
      cell layer. In eyes subjected to 60 min ischemia, there was a decrease of the
      density of calbindin D28K- (8.29%), calretinin- (14.44%), and parvalbumin-
      (26.83%) immunoreactive (IR) cells compared to the control retina. In eyes
      subjected to 90 min ischemia, there was a higher decrease of the density of
      calbindin D28K- (18.48%), calretinin- (33.59%), and parvalbumin- (54.26%) IR
      cells than at 60 min. Some calcium-binding protein-IR neurons, especially
      calretinin-IR neurons, showed aggregations that were abnormally packed together
      in retina subjected to ischemia for 90 min. The results show that calbindin D28K
      , calretinin-, and parvalbumin-IR cells in the ganglion cell layer are
      susceptible to ischemic damage and reperfusion. The degree of reduction varied
      among different calcium-binding proteins and ischemic damage times. These results
      suggest that calbindin D28K-containing neurons are less susceptible to ischemic
      damage than calretinin- and parvalbumin-containing neurons in the ganglion cell
      layer of rabbit retina.

PMID- 15995356
TI  - Molecular identification of Adoxophyes honmai (Yasuda) (Lepidoptera: Tortricidae)
      based on mitochondrial COI gene sequences.
AB  - Molecular identification techniques are used where morphological characters are
      not useful for distinguishing species that resemble each other closely. The
      example studied here is the Adoxophyes species complex, in which A. orana
      (Fischer von Rosslerstamm) is officially the only known Korean species in the
      genus Adoxophyes (Lepidoptera: Tortricidae). However there have been suspicions
      that at least two types of A. orana exist in Korea based on the distribution and
      range of the host, with A. orana attacking apples and peaches, and another
      Adoxophyes sp. attacking tea and pears. The latter is presumed to be A. honmai
      (Yasuda), but the two have remained confused because of their extreme
      morphological similarity, despite several Asian studies of pheromonal and
      morphological characteristics. To confirm the occurrence of an Adoxophyes species
      other than A. orana in Korea, we compared 940 bp of the mitochondrial cytochrome
      oxidase I (COI) gene from 16 samples of Adoxophyes and found that there is a
      second Adoxophyes species different from A. orana. Comparison of the different
      sequences to that of Japanese A. honmai confirmed that they belong to the latter.
      From the sequence difference between the two Korean species, we were able to
      develop new PCR primer sets that distinguish them. This molecular identification
      technique with no enzyme digestion or sequencing step is a convenient and rapid
      way of differentiating between species that are hard to distinguish
      morphologically.

PMID- 15995357
TI  - Crystallization and preliminary X-ray crystallographic analysis of UDP-N
      acetylglucosamine enolpyruvyl transferase from Haemophilus influenzae in complex
      with UDP-N-acetylglucosamine and fosfomycin.
AB  - The bacterial enzyme UDP-N-acetylglucosamine enolpyruvyl transferase catalyzes
      the first committed step of peptidoglycan biosynthesis, i.e., transfer of
      enolpyruvate from phosphoenolpyruvate to UDP-N-acetyl-glucosamine. We have
      overexpressed the enzyme from Haemophilus influenzae in Escherichia coli and
      crystallized it in the apo-form, as well as in a complex with UDP-N
      acetylglucosamine and fosfomycin using ammonium sulfate as the precipitant. X-ray
      diffraction data from a crystal of the apo-form were collected to 2.8 A
      resolution at 293 K. The crystal quality was improved by co-crystallization with
      UDP-N-acetylglucosamine and fosfomycin. X-ray data to 2.2 A have been collected
      at 100 K from a flash-frozen crystal of the complex. The complex crystals belong
      to the orthorhombic space group I222 (or I212121) with unit-cell parameters of a
      = 63.7, b = 124.5, and c = 126.3 A. Assuming a monomer of the recombinant enzyme
      in the crystallographic asymmetric unit, the calculated Matthews parameter (VM)
      is 2.71 A3 Da-1 and solvent content is 54.6%.

PMID- 15995358
TI  - Transfection of mesenchymal stem cells with the FGF-2 gene improves their
      survival under hypoxic conditions.
AB  - Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair
      following myocardial injury, but this approach is limited by their poor viability
      after transplantation. To reduce cell loss after transplantation, we introduced
      the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The
      isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks;
      over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific
      transcription factor, Nkx2.5, as well as a-skeletal actin, Nkx2.5, and GATA4. In
      hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased
      levels of FGF-2 and displayed a threefold increase in viability, as well as
      increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering.
      They had functional adrenergic receptors, like cardiomyocytes, and exposure to
      norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks
      after implantation of 5.0 yen 105 FGF-2-MSCs into infarcted myocardia. Expression
      of cardiac troponin T (CTn T) and a voltage-gated Ca2+ channel (CaV2.1)
      increased, and new blood vessels formed. These data suggest that genetic
      modification of MSCs before transplantation could be useful for treating
      myocardial infarction and end-stage cardiac failure.

PMID- 15995359
TI  - Immunocytochemical localization of nitric oxide synthase-containing neurons in
      mouse and rabbit visual cortex and co-localization with calcium-binding proteins.
AB  - Nitric oxide (NO) occurs in various types of cells in the central nervous system.
      We studied the distribution and morphology of neuronal nitric oxide synthase
      (NOS)-containing neurons in the visual cortex of mouse and rabbit with antibody
      immunocytochemistry. We also compared this labeling to that of calbindin D28K,
      calretinin, and parvalbumin. Staining for NOS was seen both in the specific
      layers and in selective cell types. The densest concentration of intense anti-NOS
      immunoreactive (IR) neurons was found in layer VI, while the weak anti-NOS-IR
      neurons were found in layer II/III in both animals. The NOS-IR neurons varied in
      morphology. The large majority of NOS-IR neurons were round or oval cells with
      many dendrites coursing in all directions. Two-color immunofluorescence revealed
      that only 16.7% of the NOS-IR cells were double-labeled with calbindin D28K in
      the mouse visual cortex, while more than half (51.7%) of the NOS-IR cells were
      double-labeled with calretinin and 25.0% of the NOS-IR cells were double-labeled
      with parvalbumin in mouse. By contrast, 92.4% of the NOS-IR neurons expressed
      calbindin D28K while only 2.5% of the NOS-IR neurons expressed calretinin in the
      rabbit visual cortex. In contrast with the mouse, none of the NOS-IR cells in the
      rabbit visual cortex were double-labeled with parvalbumin. The results indicate
      that neurons in the visual cortex of both animals express NOS in specific layers
      and cell types, which do not correlate with the expression of calbindin D28K,
      calretinin or parvalbumin between the two animals.

PMID- 15995360
TI  - Tobamovirus coat protein CPCg induces an HR-like response in sensitive tobacco
      plants.
AB  - When inoculated into sensitive tobacco Xanthi-nn plants, the crucifer and garlic
      infecting Tobacco mosaic virus (TMV-Cg) induces local necrotic lesions that
      resemble those seen in the hypersensitive response (HR) of resistant tobacco
      plants. However, unlike these, tobacco Xanthi-nn plants do not become resistant
      to infection and the virus spreads systemically causing a severe disease
      characterized by necrotic lesions throughout the plant. To identify the viral
      protein that elicits this necrotic response, we used a set of hybrid viruses
      constructed by combination of TMV-Cg and the tobacco mosaic virus strain U1 (TMV
      U1). In this study we present evidence that the coat protein of TMV-Cg (CPCg) is
      the elicitor of the necrotic response in tobacco Xanthi-nn plants. Local and
      systemic necrotic lesions induced by TMV-Cg and by the hybrid U1-CPCg -that
      carries CPCg in a TMV-U1 context- are characterized by cell death and by the
      presence of autoflorescent phenolic compounds and H2O2, just like the HR lesions.
      In addition, defense-related genes and detoxifying genes are induced in tobacco
      Xanthi-nn plants after TMV-Cg and U1-CPCg inoculation. We postulate that in our
      system, CPCg is recognized by sensitive tobacco plants that mount an incomplete
      defense response. We call this an HR-like since it is not enough to induce plant
      resistance.

PMID- 15995361
TI  - Use of SSR markers to complement tests of distinctiveness, uniformity, and
      stability (DUS) of pepper (Capsicum annuum L.) varieties.
AB  - This study was carried out to assess the potential of SSR markers for variety
      identification by comparing SSR markers and morphological traits in tests of
      distinctiveness, uniformity, and stability (DUS) of pepper (Capsicum annuum L.)
      varieties. Twenty-seven SSR markers were polymorphic in 66 pepper varieties,
      revealing a total of 89 alleles. Average polymorphism information content (PIC)
      value was 0.529, ranging from 0.03 to 0.877. Cluster analysis of the band
      patterns separated the varieties into three groups corresponding to varietal
      types. Morphological trait-based clustering showed some degree of similarity to
      dendrogram topologies based on the SSR index. However, no significance
      correlation was found between the SSR and morphological data. SSR markers could
      be used to complement a DUS test of a candidate variety and to select
      complimentary varieties by pre-screening existing varieties in the context of
      protecting new varieties of pepper.

PMID- 15995362
TI  - Characterization of rDNAs and tandem repeats in the heterochromatin of Brassica
      rapa.
AB  - We describe the morphology and molecular organization of heterochromatin domains
      in the interphase nuclei, and mitotic and meiotic chromosomes, of Brassica rapa,
      using DAPI staining and fluorescence in situ hybridization (FISH) of rDNA and
      pericentromere tandem repeats. We have developed a simple method to distinguish
      the centromeric regions of mitotic metaphase chromosomes by prolonged irradiation
      with UV light at the DAPI excitation wavelength. Application of this bleached
      DAPI band (BDB) karyotyping method to the 45S and 5S rDNAs and 176 bp centromere
      satellite repeats distinguished the 10 B. rapa chromosomes. We further
      characterized the centromeric repeat sequences in BAC end sequences. These fell
      into two classes, CentBr1 and CentBr2, occupying the centromeres of eight and two
      chromosomes, respectively. The centromere satellites encompassed about 30% of the
      total chromosomes, particularly in the core centromere blocks of all the
      chromosomes. Interestingly, centromere length was inversely correlated with
      chromosome length. The morphology and molecular organization of heterochromatin
      domains in interphase nuclei, and in mitotic and meiotic chromosomes, were
      further characterized by DAPI staining and FISH of rDNA and CentBr. The DAPI
      fluorescence of interphase nuclei revealed ten to twenty conspicuous
      chromocenters, each composed of the heterochromatin of up to four chromosomes
      and/or nucleolar organizing regions.

PMID- 15995363
TI  - Mechanisms underlying the effects of LPS and activation-induced cytidine
      deaminase on IgA isotype expression.
AB  - Activation-induced cytidine deaminase (AID) is needed for Ig class switch
      recombination (CSR). We explored the effect of LPS on the expression of AID
      during B cell differentiation, and the role of AID in IgA isotype expression. In
      normal spleen B cells, LPS increased AID transcription up to 48 h post
      stimulation, i.e. around the time of Ig CSR. TGF-b1 and AID were required for IgA
      expression, and LPS contributed to TGFb1-induced IgA production largely by
      inducing AID. Interestingly, LPS repressed AID transcription in sIgA+ B cells but
      still stimulated IgA production mainly by increasing the rate of IgA secretion.
      Our data indicate that LPS contributes to TGFb1-induced IgA isotype expression in
      at least two ways: by stimulating AID transcription before CSR and by enhancing
      the IgA secretion rate after CSR.

PMID- 15995365
TI  - Help put NICU nurses out of business: a new study illustrates the need to prevent
      premature births.

PMID- 15995364
TI  - The AP-3 clathrin-associated complex is essential for embryonic and larval
      development in Caenorhabditis elegans.
AB  - The adaptor protein (AP) complexes are involved in membrane transport of many
      proteins. There are 3 AP complexes in C. elegans unlike mammals that have four.
      To study the biological functions of the AP-3 complexes of C. elegans, we sought
      homologues of the mouse and human genes that encode subunits of the AP-3
      complexes by screening C. elegans genomic and EST sequences. We identified single
      copies of homologues of the m3, s3, b3 and d genes. The medium chain of AP-3 is
      encoded by a single gene in C. elegans but two different genes in mammals. Since
      there are no known mutations in these genes in C. elegans, we performed RNAi to
      assess their functions in development. RNAi of each of the genes caused embryonic
      and larval lethal phenotypes. APM-3 is expressed in most cells, particularly
      strongly in spermatheca and vulva. We conclude that the products of the C.
      elegans m3, s3, b3 and d genes are essential for embryogenesis and larval
      development.

PMID- 15995366
TI  - Where's my stuff?: small cuts may have big effects.

PMID- 15995367
TI  - Social Security.

PMID- 15995368
TI  - Social Security.

PMID- 15995369
TI  - Social Security.

PMID- 15995370
TI  - Body piercing.

PMID- 15995372
TI  - Hospital error.

PMID- 15995373
TI  - Mothers and cancer.

PMID- 15995375
TI  - A question for readers: carpets in hospitals.

PMID- 15995376
TI  - Social Security.

PMID- 15995378
TI  - Can Nurses Be Substituted for Physicians?: a recent report says they can, but it
      cannot conclude that they should.

PMID- 15995377
TI  - Social Security.

PMID- 15995379
TI  - MRSA Has Moved into the Community: a heightened level of concern.

PMID- 15995380
TI  - The fight against HIV and AIDS worldwide.

PMID- 15995381
TI  - Antihypertensive treatment and race: diuretics maintain their position as first
      line treatment.

PMID- 15995383
TI  - Urinary incontinence worsens with menopausal hormone therapy: the practice should
      be reevaluated in light of new evidence.

PMID- 15995388
TI  - Authorized and unauthorized use of PCA pumps: clarifying the use of patient
      controlled analgesia, in light of recent alerts.

PMID- 15995389
TI  - New legislation receiving ANA endorsements: Medicaid, Johanna's law, and the
      SHARE Act.

PMID- 15995390
TI  - Shipping out to the war zone: a nurse prepares for a 60-day tour of duty.

PMID- 15995391
TI  - Muffin diet: a recipe for belonging?

PMID- 15995392
TI  - Behaviors associated with dementia: whether resisting care or exhibiting apathy,
      an older adult with dementia is attempting communication. Nurses and other
      caregivers must learn to 'hear' this language.
AB  - Seemingly simple adjustments in care routines and approaches can make a
      significant difference in the experiences of people with dementia. This article
      provides an overview of cognitive impairment in older adults and suggests
      interventions that can help providers understand the "behavioral symptoms" of
      dementia, which are often considered a way of communicating unmet needs. By
      focusing on the person rather than on the disease, nurses promote comfort and
      functional autonomy in older adults whose cognitive impairments have progressed
      and yet who are very much alive and deserving of respectful, dignified care.

PMID- 15995394
TI  - Short takes on long-term care: simple pleasures: a new intervention transforms
      one long-term care facility.

PMID- 15995397
TI  - Do ask, do tell: why do so many nurses avoid the topic of sexuality?

PMID- 15995395
TI  - The cost of prematurity: hospital charges at birth and frequency of
      rehospitalizations and acute care visits over the first year of life: a
      comparison by gestational age and birth weight.
AB  - The proportion of preterm and low-birth-weight infants has been growing steadily
      for two decades. Most of the more than US 10 billion dollars spent on neonatal
      care in the United States in 2003 was spent on the 12.3% of infants who were born
      preterm. Research has shown higher initial hospital costs and a higher rate of
      acute care visits and rehospitalization for preterm and low-birth-weight infants,
      but only a limited number of studies of the cost of prematurity that follow
      infants through the first year of life have been conducted. This study is a
      secondary analysis of data on a subset of infants drawn from a randomized
      clinical trial that examined health outcomes and health care costs in women with
      high-risk pregnancies and their infants. For the current study, a sample of 84
      singleton infants was chosen. Forty-three infants (51%) were full term (37 weeks'
      gestation or more) and 41 (49%) were born preterm (less than 37 weeks'
      gestation). Fifty-five infants (65.5%) were born at normal birth weights (2,500 g
      or greater), 24 (28.5%) were born at low birth weights (1,501 to 2,499 g), and
      five (6%) were born at very low birth weights (less than 1,500 g). Data on the
      initial hospital charges and the rates of rehospitalization and acute care visits
      in the first year of life in relation to gestational age and birth weight were
      collected. The results clearly demonstrated that the charges for initial
      hospitalizations increased as birth weights and gestational ages decreased. Low
      birth-weight infants were less likely to have unscheduled acute care visits than
      normal-birth-weight infants. Interventions to improve prenatal care targeted to
      women at high risk for delivering preterm or low-birth-weight infants would
      reduce health care costs and improve health outcomes of infants as well.

PMID- 15995399
TI  - Tsunami aftermath: community regeneration is the focus of relief efforts in
      Indonesia.

PMID- 15995403
TI  - 'PTSD in nurses': the March viewpoint strikes a chord.

PMID- 15995404
TI  - Professional misconduct and professional discipline: nurses should know their
      rights and learn all they can about the disciplinary system.

PMID- 15995405
TI  - Licensure discipline: a challenge for Boards of Nursing--and nurses: being a
      professional means being accountable.

PMID- 15995406
TI  - Update: Tuberculosis in the United States: the CDC updates its guidelines, as
      infection rates decline slowly.

PMID- 15995407
TI  - The cardiovascular effects of alcohol: the good and the bad: how low-risk
      drinking differs from high-risk drinking.

PMID- 15995408
TI  - The state of the science: focus on HIV and cardiovascular disease.

PMID- 15995411
TI  - Lighting the way: luminary project proposes solutions for a safer, cleaner
      environment.

PMID- 15995413
TI  - Patellofemoral replacement. 1979.

PMID- 15995414
TI  - Development and early results of a new patellofemoral arthroplasty.
AB  - A new patellofemoral arthroplasty is described, based on a previous design of
      total knee arthroplasty. The indications are for patients with specific isolated
      patellofemoral disease with advanced chondral or arthritic damage. The design and
      technique of insertion is detailed. Three hundred six patellofemoral
      arthroplasties have been done in 240 patients. The initial results show a high
      level of pain relief and improvement in function. Two-year followup is available
      for treatment of 124 knees and 5-year followup is available for treatment of 33
      knees. There has been no deterioration in pain or function with followup to 5
      years, and there were no late complications attributable to the arthroplasty.
      Disease progression in the tibiofemoral joint has occurred in 14 patients (16
      knees, 5%) requiring revision in 10 of these patients (11 knees, 3.6%).
      Persistent anterior knee pain was recorded in 14 knees (4%). The short-term
      results using this new design were better than those of the prosthesis that we
      used previously, especially concerning malalignment and wear. It offers a
      reasonable alternative to total knee replacement in the small group of patients
      with isolated patellofemoral disease. LEVEL OF EVIDENCE: Therapeutic study, Level
      II (prospective cohort study). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 15995415
TI  - The treatment of patellofemoral osteoarthritis with partial lateral facetectomy.
AB  - We investigated the impact of the partial lateral facetectomy of the patella on
      middle-aged to elderly patients with isolated lateral patellofemoral
      osteoarthritis. Between 1991 and 2000, we performed partial lateral facetectomy
      on 11 knees in 11 patients with an average age of 62 years (range, 53-72 years).
      The mean followup was 8 years (range, 3-14). The average Knee Society Score
      improved from a preoperative score of 150 to a score of 176 at latest followup.
      Followup radiographs showed slow progression of osteoarthritis in the
      patellofemoral and tibiofemoral compartments, but radiographic appearance did not
      always correlate with clinical symptoms. The success of this procedure depends
      largely on relief of pain. Partial lateral facetectomy is relatively simple and
      effective surgical treatment for middle-aged to elderly active patients with
      isolated lateral patellofemoral osteoarthritis who want to maintain activity
      level. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series--no, or
      historical control group). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 15995416
TI  - Biomechanics of patellofemoral joint prostheses.
AB  - We describe the biomechanics of the patellofemoral joint and of patellofemoral
      joint prostheses. It seemed that the designs and associated instruments that were
      studied had little research and development and that soft tissue realignment
      procedures often were needed because of pre-existing pathology. Factors that help
      these unicompartmental implants to integrate with the surrounding knee structures
      are discussed, particularly articular geometry, contact areas, forces and
      fixation. The desirability of patellar area contact geometry rather than
      axisymmetric buttons with point or line contact is discussed, in relation to
      their use in younger more active patients. Bone preservation relating to revision
      to total knee arthroplasty also is considered. Data on the articular geometry,
      stability and tracking of the designs studied are presented, showing that
      although most parameters are returned within normal limits, problems such as
      erratic subluxation-reduction effects may occur if the patellar component catches
      on the edge of the femoral component during knee flexion-extension. Through our
      results, we suggest that further implant and instrumentation research and
      development are needed before clinical trials leading to widespread use.

PMID- 15995417
TI  - The role of autologous chondrocyte implantation in the patellofemoral joint.
AB  - In a prospective study to determine the clinical effectiveness of autologous
      chondrocyte implantation, 45 patients reached a minimum followup of 2 years
      (range, 2-7 years; average, 46.4 months) after treatment involving the
      patellofemoral articulation. There were 28 men (61%) and 17 women (39%) and the
      average age of the patients was 37.5 years (range, 15-55 years). The treatment
      groups included (I) isolated patella, n = 8; (II) isolated trochlea, n = 9; (III)
      patella plus trochlea, n = 4; (IV) weightbearing condyle plus patella n = 2; (V)
      weightbearing condyle plus trochlea, n = 2; and (VI) weightbearing condyle plus
      patella plus trochlea n = 20. The average surface area per patella (n = 34) was
      4.86 cm2 and per trochlea (n = 34) it was 5.22 cm2. The average resurfacing per
      knee (n = 45) was 10.45 cm2. We showed a postoperative improvement in quality of
      life as measured by the Short Form-36; Western Ontario and McMaster University
      Score, Knee Society Score, modified Cincinnati Score, and a patient satisfaction
      survey. There were eight failures (18%) as a result of a patella or trochlea
      failure. Seventy-one percent of patients rated their outcomes as good or
      excellent, 22% rated outcome as fair, and 7% rated outcome as poor. LEVEL OF
      EVIDENCE: Therapeutic Study, Level II-1 (prospective cohort study). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995418
TI  - A modular prosthesis for patellofemoral arthroplasty: design and initial results.
AB  - This study was designed to determine if a new and modular prosthesis for
      patellofemoral arthroplasty would produce results at least as good as those
      reported for other designs, while simultaneously eliminating the risks of
      patellar revision should total knee arthroplasty be needed in the future. Another
      issue was its suitability for the older patient with isolated patellofemoral
      arthritis in order to avoid destruction of the normal femoro-tibial compartments
      involved in total knee arthroplasty. Finally, I sought information about the
      safety and longevity of this prosthesis when used for patellofemoral arthroplasty
      in severely disabled patients too young to be considered for total knee
      replacement. From a cohort of 16 patients (8 studied retrospectively and 8
      prospectively), aged 26 to 81 years, and followed up for 2.75-6.25 years, 15
      (94%) rated their results excellent or good using the Activities of Daily Living
      Scale. These results are better than previously reported for other prosthetic
      designs. To date, no patient in this study group has required conversion to a
      total knee arthroplasty. The design has proven safe for use in both the older and
      younger patient, but longer followup will be needed to assess greater longevity.
      LEVEL OF EVIDENCE: Therapeutic Study, Level IV-8 (case series--no, or historical
      control group). See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 15995419
TI  - Long-term results with the first patellofemoral prosthesis.
AB  - We retrospectively reviewed 70 patients, representing 79 knees, who had isolated
      patellofemoral arthroplasty between 1975 and 1991 using the Richards II and III
      implants. Seventy-five percent of the prostheses were still functioning at a
      minimum of 6 and average followup of 10 years after implantation. The main cause
      of failure was secondary femorotibial osteoarthritic deterioration (8 knees).
      Only two complications of a mechanical nature related to the implant have been
      observed. Surgical revisions have not presented any particular difficulties. The
      main indication for this type of implant is advanced patellofemoral
      osteoarthritis secondary to a constitutional trochlear dysplasia occurring in a
      correctly aligned knee for which no other therapeutic procedure allows the same
      type of result to be achieved. LEVEL OF EVIDENCE: Therapeutic Study, Level IV
      (case series). See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 15995420
TI  - Patellofemoral pain: results of nonoperative treatment.
AB  - Nonoperative treatment of patellofemoral pain has a long-standing tradition of
      success. I will discuss the scientific background and practical application of
      such treatment. Evaluation and treatment should include lower extremity
      flexibility, muscular control, and careful evaluation of tender structures.
      Avoiding pain during rehabilitation is important and suggestions for this are
      included in this review. Emphasis on accurate diagnosis, careful clinical
      evaluation, activity modification, flexibility, and strengthening in creating an
      effective program are discussed and the literature is reviewed. Most patients
      should go thorough nonoperative treatment before elective surgery for
      patellofemoral pain is prescribed.

PMID- 15995421
TI  - Patellar nomenclature: the Tower of Babel revisited.
AB  - Because we communicate mainly through words, it is important that terms be
      understood in the same manner by all readers. Unfortunately, the study of the
      patellofemoral joint is complicated by the use of expressions that hold different
      meanings for different readers. Ideally, the community of musculoskeletal
      physicians should agree on a single definition of terms, but until then, authors
      and speakers should define their terms clearly. Some terms, such as
      chondromalacia and patellofemoral syndrome, should be abandoned altogether. I
      propose a glossary of confusing terms pertaining to the patellofemoral joint, the
      various interpretations of these terms, and possible resolutions of these
      conflicts. Words and terms included in this review include chondromalacia,
      patellofemoral syndrome, anterior knee pain, subluxation, malalignment, proximal
      realignment, Roux procedure, and "normal."

PMID- 15995422
TI  - Outcome instruments for patellofemoral arthroplasty.
AB  - Although there are numerous patient outcome instruments available, the most
      reliable and valid instruments for evaluating patient outcomes after
      patellofemoral arthroplasty have not been identified. In this article, we review
      and evaluate the psychometric properties and practical considerations of
      administering general health instruments (Medical Outcomes Study (MOS) Short Form
      36 and Short Form-12), knee scales (Knee Society Clinical Rating System, Knee
      Outcome Survey, International Knee Documentation Committee form, Knee Injury and
      Osteoarthritis Outcome Score) and a disease specific scale (Western Ontario and
      McMaster Universities Osteoarthritis Index) for patellofemoral arthroplasty
      outcome assessment. Based on our review of the literature, we recommend the Short
      Form-36 and Knee Injury and Osteoarthritis Outcome Score for evaluation of
      patellofemoral arthroplasty outcomes and provide recommendations for
      implementation of these instruments in a clinical setting.

PMID- 15995423
TI  - Anatomy and malalignment of the patellofemoral joint: its relation to
      patellofemoral arthrosis.
AB  - Patellofemoral joint function involves a complex orchestration of a number of
      dynamic, static, and neuromuscular factors. I will discuss the components of
      patellofemoral anatomy and whether the presence of certain anatomic variables may
      increase the risk of patellofemoral arthrosis. The patellofemoral surgeon is
      faced with several clinical challenges: the semantics of the language used to
      discuss these problems, the correlation of clinical symptoms and radiographic
      imaging to help diagnose a problem, and surgical challenges in optimizing
      extensor mechanism function.

PMID- 15995424
TI  - Alternatives to patellofemoral arthroplasty.
AB  - When surgical intervention becomes necessary in the treatment of a patient with
      isolated patellofemoral arthritis, the primary alternatives to arthroplasty are
      tubercle anteriorization or anteromedialization, patellectomy, and cartilage
      transplantation. The relative merits of these options should be discussed with
      each patient. There must be healthy central and proximal patella cartilage in
      order to expect a good result from a tibial tubercle anteriorization.
      Patellectomy leaves a well-defined functional deficit and therefore is better to
      avoid whenever possible, although relief of pain after patellectomy can be
      substantial. Cartilage resurfacing of the trochlea is an attractive alternative.
      Combining a resurfacing procedure with decompression of the joint by anteromedial
      or anterior tibial tubercle transfer should help protect the resurfaced area.
      Replacement of the patellofemoral joint, properly done on a well aligned extensor
      mechanism, is most attractive when both patella and trochlea are deficient or
      when an alternative procedure is unacceptable.

PMID- 15995426
TI  - The appropriate use of patellofemoral arthroplasty: an analysis of reported
      indications, contraindications, and failures.
AB  - Patellofemoral arthroplasty is going through a recent resurgence in interest with
      various new designs being introduced for general orthopaedic use. With this
      renewed enthusiasm for the procedure, it is important to understand the various
      indications and contraindications for using patellofemoral arthroplasty devices
      with the expectation that proper patient selection will improve outcome. Our
      purpose was to analyze the appropriate usage of these prostheses based on
      published historical results. A literature search was done to review the
      indications, contraindications, and factors contributing to the failure of these
      devices. We analyzed 12 studies reporting results of patellofemoral arthroplasty
      between 1979 and 2005. Commonly cited contraindications for using these devices
      have been tibiofemoral arthritis, uncorrected patellofemoral or tibiofemoral
      malalignment, and inflammatory arthritis. The highest failure rates were in
      patients with progression of osteoarthritis in other compartments or persistence
      of congenital or surgically uncorrected malalignment. In analyzing the reasons
      for failures in these reports together with issues already known to affect total
      knee arthroplasty surgery, we suggest an expanded list of outcome-altering
      factors to consider when choosing to do a patellofemoral arthroplasty. Finally,
      based on these observations and our own experience, suggestions on the best
      approach to the patient with patellofemoral arthritis are made to avoid less than
      optimal results if patellofemoral arthroplasty is considered. LEVEL OF EVIDENCE:
      Prognostic Study, Level II-3 (systematic review of Level-II studies. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995427
TI  - The pathophysiology of patellofemoral pain: a tissue homeostasis perspective.
AB  - Fundamental to rational, safe, and effective treatment for any orthopaedic
      condition is an accurate understanding of the etiology of the symptoms. The
      decades-old paradigm of a pure structural and biomechanical explanation for the
      genesis of patellofemoral pain is giving way to one in which biologic factors are
      being given more consideration. It is increasingly evident that a variable mosaic
      of possible pathophysiologic processes, often caused by simple overload, best
      accounts for the etiology of patellofemoral pain in most patients. Inflamed
      synovial lining and fat pad tissues, retinacular neuromas, increased intraosseous
      pressure, and increased osseous metabolic activity of the patella all have been
      documented as contributing to the perception of anterior knee pain. Considered
      together, these processes can be characterized as loss of tissue homeostasis and
      can be seen as providing a new and alternative explanation for the conundrum of
      anterior knee pain. Certain high loading conditions of the patellofemoral joint
      can be of sufficient magnitude to induce the symptomatic loss of tissue
      homeostasis so that, once initiated, they may persist indefinitely. From this new
      biologic perspective, it clinically matters little what structural factors may be
      present in a given joint (such as chondromalacia, patellar tilt or a Q angle
      above a certain value) if the pain free condition of tissue homeostasis is safely
      achieved and maintained. LEVEL OF EVIDENCE: Level V (expert opinion). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995425
TI  - Patellofemoral joint biomechanics and tissue engineering.
AB  - Recent advances in the study of patellofemoral joint biomechanics have provided
      promising diagnosis and treatment modalities for patellofemoral joint disorders,
      such as quantitative assessment of cartilage lesions from noninvasive imaging,
      computer simulations of surgical procedures for optimizing surgical parameters
      and potentially predicting outcomes, and cartilage tissue engineering for the
      treatment of advanced degenerative joint disease. These technologies are still in
      development and their clinical potentials remain an ongoing topic of
      investigation. We review some of our progress in addressing these issues, and the
      important role of cartilage mechanics and lubrication in understanding the
      challenges regarding patellofemoral surgery and cartilage tissue engineering.

PMID- 15995428
TI  - The long-term results of a metal-backed mobile bearing patella.
AB  - Enthusiasm for metal-backed patella has waned because of the high incidence of
      complications. Considering that perhaps all metal-backed patellae may not be the
      same, 256 primary consecutive metal-backed mobile bearing TKAs done between May
      1985 and January 1989 were retrospectively reviewed to evaluate the results of a
      unique mobile bearing metal-backed patella. There were four complications (1.6%).
      Three patella were revised for polyethylene complications and one well
      functioning component was removed at the time of revision of the tibial
      polyethylene to facilitate range of motion and wound closure. No patella was
      revised for loosening, subluxation, or dislocation. Our results show that all
      metal-backed patella are not the same and that compared with the high incidence
      of failure of fixed bearing metal-backed patellae, the use of the anatomic mobile
      bearing metal-backed patella can produce excellent, durable long-term clinical
      and radiographic results with a low incidence (1.6%) of complications. Life table
      survivorship using revision for any reason as the end point was 97% (95%
      confidence interval, 93%-100%) at a maximum of 19 years. LEVEL OF EVIDENCE:
      Therapeutic study, Level IV (case series--no, or historical control group). See
      the Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995429
TI  - Transpedicle body augmenter: a further step in treating burst fractures.
AB  - The efficiency of short-segment fixation with a transpedicle body augmenter for
      treatment of thoracolumbar burst fractures was retrospectively evaluated.
      Patients included in the study had limited neurologic function, a single-level
      burst fracture involving T11-L2, and no distraction or rotation trauma. Patients
      in the control group (n = 45) were treated with short-segment posterior
      instrumentation alone, whereas patients in the augmented group (n = 75) were
      treated with a titanium block designed for transpedicle body reconstruction. The
      followup was 24-70 months. The operation time and blood loss were similar in both
      groups. The immediate postoperative anterior vertebral restoration rate of the
      augmented group was similar to that of the control group (96.8% +/- 2.1% versus
      96.7% +/- 3.0%). The final anterior vertebral restoration was greater in the
      augmented group than in the control group (93.7% +/- 3.0% versus 66.3% +/-
      10.5%). Immediate postoperative kyphotic angles were not significantly different
      between the groups (3.2 degrees +/- 1.5 degrees versus 5.5 degrees +/- 2.0
      degrees). The final kyphotic angles were less in the augmented group than the
      control group (6.7 degrees +/- 3.0 degrees versus 19.6 degrees +/- 5.1 degrees).
      The control group had more implant failures than the augmented group. The
      augmented group had better results according to the Denis pain scale. Posterior
      body reconstruction with a transpedicle body augmenter can maintain kyphosis
      correction and vertebral restoration, prevent implant failure, and lead to better
      clinical results. LEVEL OF EVIDENCE: Therapeutic study, Level III-2
      (retrospective cohort study). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 15995430
TI  - Anatomic study of the semispinalis cervicis for reattachment during laminoplasty.
AB  - Some patients who had cervical laminoplasty with subsequent substantial loss of
      cervical lordosis have shown failed healing of a repaired semispinalis cervicis.
      We also have identified some patients in whom it is difficult to repair the C2
      spinous process during laminoplasty. We therefore quantitatively analyzed the
      morphologic features of the C2 insertion of the semispinalis cervicis and
      obtained data relevant to the repair of the muscle. In 24 cadavers, the width and
      height of the semispinalis cervicis insertion in C2 and the length and opening
      angle of the C2 spinous process were measured. We observed considerable
      individual variations in the morphologic features of the C2 spinous process and
      the C2 insertion of the semispinalis cervicis. The opening angle of the C2
      spinous process was smaller in males than in females. In most of the cases, the
      width of the insertion was narrower than the width of the spinous process spacers
      that commonly are used in laminoplasty. Preoperative prediction of the
      morphologic features of insertion at the original site is possible by measuring
      the opening angle of the C2 spinous process using three-dimensional computed
      tomography because the muscle insertion correlated with the angle of the C2
      spinous process. This information may be useful in reattaching the semispinalis
      cervicis during cervical laminoplasty.

PMID- 15995431
TI  - Implant migration after early weightbearing in cementless hip replacement.
AB  - Twenty-nine patients (five women and 24 men) with an average age of 47 years
      (range, 24-59 years) had 37 total hip arthroplasties using a hydroxyapatite
      coated double-wedge press-fit femoral component. All patients had a Type A bone
      quality. Patients were either mobilized with weightbearing as tolerated or toe
      touch weightbearing for 6 weeks postoperatively. After 6 weeks all patients were
      advanced to weightbearing as tolerated. Radiostereometric analysis radiographs
      were taken at 3 days, 6 weeks, and 6 months postoperatively to measure migration
      of the femoral component. Radiostereometric analysis revealed no difference in
      stem migration between the two groups as defined by maximal total point
      migration. There was a difference in the vertical (proximal-distal) migration
      within the first 6 weeks between groups (0.81 mm versus 0.13 mm), but not
      afterwards (0.17 mm versus 0.18 mm). Continuous migration after 6 weeks was
      observed in three patients from each group. There was no loosening in either
      group within a 2-year followup. Weightbearing as tolerated is recommended for
      young patients with excellent bone quality after cementless total hip
      arthroplasty with a double-wedge press-fit femoral component. LEVEL OF EVIDENCE:
      Diagnostic study, Level I (testing of previously developed diagnostic criteria in
      series of consecutive patients--with previously applied reference gold standard).
      See the Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995432
TI  - Thromboembolic disease prophylaxis in total hip arthroplasty.
AB  - We sought to determine if using aspirin and exercise as prophylaxis against
      thromboembolic disease in patients having total hip arthroplasties would provide
      results as effective as or better than those reported in the literature using
      other chemical agents. One thousand eight hundred thirty-five total hip
      arthroplasties were done in 1585 patients using a posterior approach. Surgery was
      done with the patient under general anesthesia in 459 instances and regional
      anesthesia in 1376 instances. Graduated elastic stockings were used in 1117
      instances and intermittent compression stockings were used in 718 instances.
      Passive exercises of the major joints of the operated extremity were done
      intraoperatively, and active exercises were done postoperatively. Patients
      received a suppository containing 10 grains of aspirin immediately after surgery
      and 325 mg twice a day for the length of their hospitalization. Fatal pulmonary
      embolism developed after two (0.10%) surgical procedures. Nonfatal pulmonary
      embolisms were diagnosed in 17 (0.9%) patients, and deep venous thrombosis was
      diagnosed in 17 (0.9%) patients. The low incidence of thromboembolic
      complications recorded in this series suggests that our postoperative protocol,
      including 325 mg of aspirin twice a day during hospitalization and exercise, is
      an effective and inexpensive method of prophylaxis after total hip arthroplasty.
      LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series--no, or historical
      control group). See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 15995433
TI  - Anatomic referencing of cup orientation in total hip arthroplasty.
AB  - Pelvic tilt and rotation can drastically affect the apparent cup orientation on
      conventional anteroposterior pelvic radiographs. It was hypothesized that
      nonstandardized radiographic cup version and abduction can differ significantly
      from the corresponding anatomic angles if not measured to the anterior pelvic
      plane, defined by the pubic tubercles and the anterior superior iliac spine.
      Differences in preoperative and postoperative pelvic orientation and their
      influence on radiographic measurements of the two angles were analyzed.
      Conventional radiographs and preoperative and postoperative computed tomography
      scans of 37 total hip arthroplasties were compared. Calculations were made with
      the preoperative planning station of a computer navigation system. Significantly
      smaller values of cup version were seen on nonstandardized radiographs, whereas
      abduction could be measured reliably when referenced to horizontal pelvic
      landmarks seen on radiographs. The underlying cause for this difference was the
      variation of pelvic tilt that ranged 27 degrees (range, -7 degrees -20 degrees).
      Influence of pelvic tilt on the apparent cup orientation can be seen with simple
      nomograms. The orientation of the anterior pelvic plane before and after surgery
      did not differ. We think that version measurement on nonstandardized radiographs
      without anatomic referencing is highly inaccurate. LEVEL OF EVIDENCE: Diagnostic
      study, Level II-1 (development of diagnostic criteria on basis of consecutive
      patients--with universally applied reference "gold" standard). See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 15995434
TI  - Acetabular augmentation ring for recurrent dislocations in revision arthroplasty.
AB  - We retrospectively reviewed 18 patients with recurrent dislocations after
      revision total hip arthroplasty with no identifiable specific cause. All patients
      were treated with an acetabular component augmentation ring to evaluate whether
      the acetabular augmentation ring effectively decreases the redislocation rate
      compared with other treatment options. The acetabular augmentation ring was
      implanted after an average of 4.9 dislocations and failed nonoperative or
      surgical treatment. Seven patients had postoperative complications, including
      four patients with persistent neurologic deficits. The average followup was 35.1
      months (range, 24-52 months). During followup six patients experienced a
      dislocation. Four patients and three patients presented with implant loosening
      and deep infection, respectively. Overall, 10 patients had surgical revision and
      removal of the acetabular augmentation ring during followup. The remaining eight
      patients, who did not require additional surgical intervention, had an average
      Harris hip score of 42.5 (range, 9.5-61.7). The use of an acetabular augmentation
      ring is not supported by results of our study. LEVEL OF EVIDENCE: Therapeutic
      study, Level IV (case series--no, or historical control group). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995435
TI  - A rough surface finish adversely affects the survivorship of a cemented femoral
      stem.
AB  - To assess the role of surface finish in the survivorship of a cemented femoral
      stem, we evaluated the midterm clinical and radiographic performances of a cohort
      of patients who had total hip arthroplasties with two cemented femoral stems that
      differed only in surface finish. One hundred seventy-five patients [64 total hip
      arthroplasties with rough, textured stems (radius, 1.75-2.5 microm) and 138 total
      hip arthroplasties with satin finish, textured stems (radius, 0.5 microm)] were
      followed up clinically and radiographically for 4-8 years. All surgeries were
      done by one surgeon using the same surgical technique, acetabular cup, cement
      type, and cementing technique. The groups had similar demographics, diagnoses,
      preoperative clinical scores, cement mantle qualities, alignments, and lengths of
      followup. Seven hips in the rough surface group and none in the satin surface
      group had aseptic loosening. The femoral bone-cement interface showed progressive
      radiolucent lines or osteolysis in eight of 64 rough stems and in three of 138
      satin stems. A rough, textured stem of this design is more likely to fail at
      intermediate followup than a satin surface stem. We recommend that the surface of
      cemented stems should be satin or polished with a radius less than 0.5 microm.
      LEVEL OF EVIDENCE: Therapeutic study, Level III-1 (case-control study). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995436
TI  - Alumina ceramic bearings for total hip arthroplasty: five-year results of a
      prospective randomized study.
AB  - Three hundred twenty-eight ceramic bearings were implanted by six surgeons in 316
      patients as a part of a prospective randomized US Investigational Device
      Exemption study comparing alumina ceramic bearings with cobalt chrome-on
      polyethylene bearings. There was no difference between the control metal-on
      polyethylene and the alumina bearing couple patient cohorts regarding
      demographics or clinical scores through 7 years. Revision for any reason occurred
      in 2.7% of the patients with alumina bearings and 7.5% of the control patients
      with polyethylene bearings. Osteolysis was found in 1.4% of the patients with
      alumina bearings and in 14.0% of the control patients. At an average followup of
      5.0 years (range, 1-86 months) no ceramic fractures or ceramic bearing failures
      have occurred. Results of this study suggest that alumina ceramics perform as
      well as the metal-on-polyethylene in clinical scores, but the patients with
      ceramic bearings had fewer revisions and less osteolysis. These results lead us
      to think that this new alumina ceramic bearing provides a safe option for younger
      and more active patients. LEVEL OF EVIDENCE: Therapeutic study, Level I-1b
      (randomized controlled trial, no significant difference, but narrow confidence
      intervals). See the Guidelines for Authors for a complete description of levels
      of evidence.

PMID- 15995437
TI  - Variability of extraarticular tibial rotation references for total knee
      arthroplasty.
AB  - Anatomic reference axes that determine rotational alignment of the tibial
      component have not been established. To assess variability of three anatomic
      reference axes (a new tibial anteroposterior axis that we proposed, the
      transmalleolar axis of the ankle, and the second metatarsus bone axis of the
      foot), we measured the angles between a defined anteroposterior axis of the tibia
      (a line perpendicular to the transepicondylar axis) and each of the three axes in
      57 knees of healthy subjects using computed tomography scans. The angle between
      the defined anteroposterior axis and our proposed anteroposterior axis (a line
      connecting the middle of the posterior cruciate ligament and the medial edge of
      the patellar tendon attachment) averaged -0.2 degrees +/- 2.8 degrees (range, 
      5.5 degrees -6.3 degrees). The angle between the defined anteroposterior axis and
      the transmalleolar axis averaged 25.9 degrees +/- 9 degrees (range, 8 degrees 
      49.4 degrees), and the angle between the defined anteroposterior axis and the
      second metatarsus bone axis averaged 5.2 degrees +/- 10 degrees (range, -21.9
      degrees -24 degrees). The variability of the anteroposterior axis was less than
      than the other reference axes. These data indicate that our proposed tibial
      anteroposterior axis is more reliable for determining rotational alignment of the
      tibial component in total knee arthroplasty.

PMID- 15995438
TI  - Cruciate-retaining total knee arthroplasty at 5 to 7 years followup.
AB  - Cruciate-retaining total knee implants may improve postoperative function in
      total knee arthroplasty, but whether patients experience good restoration of
      kinematics, undue wear, or increased revision rates is debatable. I evaluated
      clinical results, radiographs, and survival rates of the NexGen posterior
      cruciate-retaining implant at 5-7 years followup in 251 knees (198 patients) in a
      prospective, consecutive total knee replacement series done from 1996-1997. A
      consistent improvement in knee scores and range of motion was observed from
      preoperative evaluation through 5 years followup. Alignment remained constant and
      knee stability did not deteriorate. Knee Society scores were good or excellent
      for 90% of patients. The average range of motion was 123 degrees, and 73% of
      patients achieved a mean range of motion of 116 degrees -130 degrees. Mean
      physical quality of life measures improved from preoperative evaluation to the
      last followup. There were no complete or progressive radiolucencies. Four screw
      radiolucencies had progressive increases in diameter. Survival of the implant at
      7 years was more than 98%. The NexGen posterior cruciate-retaining implant
      provided satisfactory kinematic and clinical results with no substantive
      polyethylene wear. LEVEL OF EVIDENCE: Therapeutic study, Level II-2 (poor-quality
      randomized controlled trial). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 15995439
TI  - Epinephrine-augmented hypotensive epidural anesthesia replaces tourniquet use in
      total knee replacement.
AB  - Tourniquets commonly are used during total knee arthroplasties to reduce
      intraoperative blood loss, despite their various side effects. The goal of this
      study was to determine whether tourniquet use could be avoided using epinephrine
      augmented hypotensive epidural anesthesia during a total knee arthroplasty
      without negative effects on perioperative hemoglobin values. One hundred patients
      having total knee arthroplasties were included in a prospective, observer
      blinded, controlled, and randomized study. Forty-nine patients received
      epinephrine-augmented hypotensive epidural anesthesia without use of a tourniquet
      (Group A), and 51 patients received normotensive epidural anesthesia with use of
      a tourniquet (Group B). Hemoglobin was evaluated and is reported preoperatively,
      immediately and 6 hours postoperatively, and on Days 1, 2, 3, 5, and 6 in
      absolute and relative values. Data were not collected for Day 4. Greater absolute
      and relative postoperative hemoglobin values were observed in Group A immediately
      postoperative, on Day 5, and on Day 6. In patients who did not have transfusions,
      the mean relative hemoglobin values were greater in Group A at all times
      evaluated (except on Day 1). Epinephrine-augmented hypotensive epidural
      anesthesia is an effective method to avoid the use of a tourniquet during total
      knee arthroplasty without the negative effects on perioperative hemoglobin
      values. LEVEL OF EVIDENCE: Therapeutic study, Level I-1a (randomized controlled
      trial, significant difference). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 15995440
TI  - Differences in the Risser grading systems in the United States and France.
AB  - A grading system for ossification of the iliac apophysis (Risser sign) came into
      use in the mid 1950s in the United States and was adopted sometime later with
      modifications in France and other European countries. Although called by the same
      name, these systems have important differences that could lead to different
      choices of how and when to treat patients with spinal deformity. In a
      retrospective study, two experienced examiners (FDB and KPV) independently
      reviewed 301 randomly selected spine radiographs from 167 patients with
      adolescent idiopathic scoliosis and graded them for bilateral iliac crest
      apophyseal excursion each using a different system. The two grading systems were
      compared using percent agreements and kappa statistics. There was good to
      excellent agreement between the two Risser systems in only 50.8% of the patients.
      In disagreements regarding 147 of 148 patients, the US Risser grade was higher
      than the French Risser grade. In 130 of these patients (88.5%) the disagreement
      was one grade, and in 17 patients (11.5%), it was two grades. Therefore, the
      French Risser grading system uniformly undervalued the ossification excursion
      compared with the US Risser grading system. We think that the observed
      discordance is a source of miscommunication and descriptive confusion in the
      literature and in patient treatment. LEVEL OF EVIDENCE: Diagnostic study, Level
      III-1 (study of nonconsecutive patients--no consistently applied reference gold
      standard). See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 15995441
TI  - Prognostic relevance of clinical symptoms in patients with spinal metastases.
AB  - Medical and surgical advances allow surgical treatment of many patients with
      spinal metastases. Although emerging surgical techniques facilitate stabilization
      of the collapsed spine, surgical candidates should be carefully selected.
      However, the lack of confirmed criteria to determine survival of these patients
      makes selection for surgery difficult. Clinical symptoms have been considered
      possible factors associated with prognosis, but their relevance has not been
      confirmed because of inadequate power for proper statistical analysis. We
      retrospectively reviewed 165 patients who had surgery for spinal metastases from
      various cancers. Clinical symptoms including pain, paresis, and walking status
      were recorded. Multivariate analysis indicated that the histologic type of the
      primary tumor was the strongest prognostic factor, followed by preoperative
      paresis and pain. Myeloma, thyroid cancer, renal cell cancer, breast cancer, and
      prostate cancer had better prognoses than other kinds of cancer. Patients without
      paresis before surgery had a better prognosis than patients with paresis, and
      patients with no pain before surgery had a better prognosis than those with pain.
      Preoperative walking status was not an independent prognostic factor. LEVEL OF
      EVIDENCE: Therapeutic study, Level IV (case series--no, or historical control
      group). See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 15995442
TI  - Arthrodesis of the shoulder after tumor resection.
AB  - Functional outcomes of patients with arthrodesis after resection of a shoulder
      girdle neoplasm are only sparsely reported. Fusion of the shoulder can be done as
      a primary reconstruction or secondarily for salvage of a failed limb-sparing
      procedure. We retrospectively reviewed 21 patients at a mean followup of 11
      years. In eight patients, arthrodesis was done as the primary reconstruction and
      in 13 patients as the secondary procedure. There were no local recurrences, and
      no patient had metastatic disease develop. The overall Toronto extremity salvage
      and Musculoskeletal Tumor Society scores were 81% (range, 46-97) and 23 points
      (range, 17-26), respectively. There was no difference with respect to function
      between patients who had their arthrodesis as a primary or secondary procedure.
      Eight of 21 patients (43%) had a complication that required major surgical
      intervention. Shoulder arthrodesis as a limb salvage procedure after tumor
      resection provides good function independent of whether the procedure is done
      primarily or secondarily. Because of the high complication rate, future efforts
      must be directed at surgical methods to decrease such complications. LEVEL OF
      EVIDENCE: Therapeutic study, Level IV (case series--no, or historical control
      group). See the Guidelines to Authors for a complete description of levels of
      evidence.

PMID- 15995443
TI  - Factors affecting ambulatory status and survival of patients 90 years and older
      with hip fractures.
AB  - This study was done to assess the long-term functional outcome of very elderly
      patients with hip fractures, to determine whether bone mineral density and
      prevalent vertebral fractures could affect mortality and ambulatory status, and
      to examine which patient characteristics reported in the literature are
      predictive of patient mortality and ambulatory status. Seventy-four patients 90
      years and older with hip fractures were analyzed and followed up for at least 4
      years or until death. The mean age of the patients was 92.8 years and all were
      treated surgically. Walking ability before injury was better than at discharge;
      walking ability decreased during the first year after discharge, but thereafter
      reached a plateau. The predictors of survival were the preoperative American
      Society of Anesthesiologists score, walking ability, fracture type, type of
      surgery, and the number of prevalent vertebral fractures on admission. Dementia
      and the number of prevalent vertebral fractures were predictors of the recovery
      of walking ability. Type of surgery and fracture type are collinear variables,
      and because it is difficult to separate the effects of one versus the other,
      additional well-designed, randomized studies on the effect of the type of surgery
      and fracture type on outcome are needed. LEVEL OF EVIDENCE: Prognostic study,
      Level II-1 (retrospective study). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 15995444
TI  - Radiographic measurements do not predict syndesmotic injury in ankle fractures:
      an MRI study.
AB  - Several radiographic measurements have been described and are used to determine
      ligamentous injury in ankle fractures, particularly of the deltoid and
      syndesmosis complex. Because the accuracy of these radiographic measurements has
      been questioned, we sought to evaluate their accuracy using magnetic resonance
      imaging as an indicator for injury. Seventy patients with closed ankle fractures
      were entered prospectively into the study, and all had standard plain
      radiographic evaluations before reduction (anteroposterior, lateral, and mortise)
      and magnetic resonance imaging. Four radiographic measurements were made on
      initial ankle injury films: tibiofibular clear space on the anteroposterior view,
      tibiofibular overlap on the anteroposterior and mortise views, and medial clear
      space on the mortise view. These radiographic measurements and their association
      with magnetic resonance imaging findings then were analyzed. A medial clear space
      measurement greater than 4 mm correlated with disruption of the deltoid and the
      tibiofibular ligaments. We found no association between the tibiofibular clear
      space and overlap measurements on radiographs with syndesmotic injury on magnetic
      resonance imaging scans. LEVEL OF EVIDENCE: Prognostic study, Level II-1
      (retrospective study). See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 15995445
TI  - Treatment of femoral nonunions by using cyclic compression and distraction.
AB  - Eleven patients with femoral diaphyseal nonunions after intramedullary nailing
      were treated with cyclic compression and distraction with an external fixator
      over the nail. We evaluated the limitations of this technique and whether
      patients having this closed procedure could achieve union without additional
      operative procedures. Patients with hypertrophic nonunions (n = 4) were treated
      with gradual compression of the nonunion site. Cyclic compression and distraction
      was done in patients with oligotrophic (n = 2) or atrophic nonunions (n = 5) to
      stimulate consolidation. The average age of the patients was 32.9 years (range,
      21-48 years), and the average followup was 40.5 months (range, 24-64 months).
      Union was achieved in an average of 5.8 months in all patients after one
      operation and without additional surgical intervention. However, pain
      necessitating strong analgesic agents and pin-related complications consisting of
      osteomyelitis, septic arthritis, and pin breakage in the atrophic nonunion group
      were a major limitation of this technique. Based on our study, the cyclic
      compression and distraction technique can be used in hypertrophic and
      oligotrophic nonunions that have failed one or more prior exchange nailings.
      However, it might not be an option for treatment of patients with atrophic
      nonunions unless pin-site problems are resolved. LEVEL OF EVIDENCE: Therapeutic
      study, Level IV (case series--no, or historical control group). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995446
TI  - Implications of the pivot shift in the ACL-deficient knee.
AB  - The Losee repair controls rotational subluxation of the lateral femoral condyle,
      or pivot shift, but does not reliably eliminate Lachman laxity. Despite this
      surgical limitation, many patients who were operated on continued to do high
      demand activities at the last followup. We hypothesized that Lachman findings
      alone did not predict poor surgical outcome or progression to osteoarthritis. We
      report on 87 patients evaluated at an average of 9 years (range, 5-21 years)
      postoperatively. Prospectively collected examinations and radiographic,
      subjective, and objective outcome measures were recorded and statistically
      evaluated. The presence of a postoperative pivot shift or residual varus laxity
      correlated with poor patient subjective evaluations and poor scoring outcomes.
      Lachman laxity with an absent pivot shift had no correlation with the outcome
      measures or onset of radiographic progression to osteoarthritis. Meniscectomy,
      additional knee surgery, increased valgus or varus laxity, and time from injury
      until the final radiograph positively correlated with the onset of
      osteoarthritis. Elimination of the pivot shift was necessary to achieve
      successful relief of symptoms and functional outcome. In the absence of a pivot
      shift, Lachman laxity was not solely predictive of poor outcomes. LEVEL OF
      EVIDENCE: Prognostic study, Level II-1 (retrospective study). See the Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 15995447
TI  - Clinical outcome of autologous chondrocyte implantation at 5 years in US
      subjects.
AB  - Peterson's pioneering experience with the first clinical application of
      autologous chondrocyte implantation showed improvement in clinical outcomes,
      durable as much as 11 years, for a difficult patient population. An assessment of
      the general applicability of this technology in the United States requires long
      term, multicenter followup. The purpose of this multicenter cohort study was to
      assess the clinical outcomes of patients treated with autologous chondrocyte
      implantation for lesions of the distal femur. Modified 10-point scales of the
      Cincinnati knee rating system were used to measure outcomes assessments at
      baseline and at 5 years. Eighty-seven percent (87 of 100) of patients completed 5
      year followup assessments. Patients were an average 37 years of age, had a mean
      total defect size of 4.9 cm2, and had low baseline overall condition scores. At
      least one prior cartilage repair procedure had failed in 70% of the patients. At
      followup, 87 patients reported a mean improvement of 2.6 points in the overall
      condition score, including 62 with improved conditions, six with no change in
      condition, and 19 with worsened conditions. Of the 62 patients who improved, the
      mean overall condition score improved 4.1 points at followup. Patients treated
      with autologous chondrocyte implantation for large cartilage defects in the
      distal femur reported improvement in outcome scores at 5 years followup. LEVEL OF
      EVIDENCE: Therapeutic study, Level II-1 (prospective cohort study). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 15995448
TI  - A model for chronic osteomyelitis using Staphylococcus aureus in goats.
AB  - Animal models of osteomyelitis traditionally have been characterized by inherent
      weaknesses related to animal size, differences in clinical findings compared with
      humans, aggressive behavior, high complication rate, and high cost. In this
      experiment, a model of tibial osteomyelitis was established in 28 goats with a
      very low complication rate and a consistent clinical, radiographic, and
      histologic disease course. The infecting Staphylococcus aureus organism was
      isolated in all but five of 28 animals (82%), in which there was no growth of
      bacteria at 24 and 72 hours. All five of these specimens had histologic evidence
      of osteomyelitis. Twenty-seven of the 28 animals (96%) had radiographic and
      histologic evidence of osteomyelitis. Clinical progression of the disease was
      observed by draining wounds, a postoperative limp that subsided in all goats, and
      varied periods of anorexia despite an average increase in body weight. There were
      no complications or mortalities related to the establishment of the animal model.
      This large animal model will provide a practical method of studying osteomyelitis
      and comparing treatment protocols.

PMID- 15995449
TI  - Understanding the biology of compressive neuropathies.
AB  - Compressive neuropathies are highly prevalent, debilitating conditions with
      variable functional recovery after surgical decompression. Chronic nerve
      compression injury induces concurrent Schwann cell proliferation and apoptosis in
      the early stages of the disorder, independent of axonal injury. These
      proliferating Schwann cells locally demyelinate and remyelinate in the region of
      injury. Furthermore, Schwann cells upregulate vascular endothelial growth factor
      secondary to chronic nerve compression injury and induce neovascularization to
      facilitate the recruitment of macrophages. In contrast to Wallerian degeneration,
      macrophage recruitment occurs gradually with chronic nerve compression injury and
      continues for a longer time. Schwann cells change their gene and protein
      expression in response to mechanical stimuli as shear stress decreases the
      expression of myelin associated glycoprotein and myelin basic protein mRNA and
      protein for in vitro promyelinating Schwann cells. The local down-regulation of
      myelin associated glycoprotein in the region of compression injury creates an
      environment allowing axonal sprouting that may be reversed with intraneural
      injections of purified myelin associated glycoprotein. These studies suggest that
      while the reciprocal relationship between neurons and glial cells is maintained,
      chronic nerve compression injury is a Schwann cell-mediated disease.

PMID- 15995451
TI  - Periprosthetic patellar fracture after an open knee dislocation.
AB  - We present a patient who sustained an open knee dislocation with a periprosthetic
      fracture of the patella and who was treated satisfactorily with tension band
      wiring and a conservative rehabilitation program. In addition to describing this
      unique combination of injuries, we review the literature on the treatment of
      periprosthetic patellar fractures. Although internal fixation of these fractures
      historically has provided unpredictable results, we think that it is warranted if
      the patella has adequate bone stock.

PMID- 15995450
TI  - Tumoral calcinosis in infants: a report of three cases and review of the
      literature.
AB  - Tumoral calcinosis is the deposition of calcium crystals and salts in the
      periarticular soft tissues. It commonly is seen as a complication of renal
      dialysis or in patients with a hereditary disposition. Occasionally, it is seen
      as an isolated condition with no known cause. Tumoral calcinosis usually affects
      adults and rarely, children. This disorder is extremely uncommon in infants. Only
      13 cases have been reported. In this study three additional infants with tumoral
      calcinosis are reported, bringing the total to 16 cases. These 16 cases provide
      the opportunity to compare tumoral calcinosis in infants (younger than 18 months)
      with the disease in older patients. Although histologic and radiologic features
      in infants and adults are identical, some clinical features differ. In almost all
      infants, the disease develops without any predisposing factors, such as a family
      history. Surgical removal of lesions in infants is curative. By contrast, lesions
      in adults tend to recur after surgery.

PMID- 15995452
TI  - Mixed sclerosing dysplasia of the bone associated with ovarian and skin problems.
AB  - The clinical, radiologic, histopathologic, and genetic features of a sclerosing
      bone dysplasia found in three members of a family are described. The bone
      disorder affected all metaphyseal-diaphyseal regions of all long bones, the
      skull, and three metacarpals. All affected members also had ichthyosis vulgaris
      and premature ovarian failure. These features have not been reported before,
      indicating a new syndrome.

PMID- 15995453
TI  - Shoulder pain and mass in a 22 year-old-man.

PMID- 15995454
TI  - Extracorporeal support for organ donation after cardiac death effectively expands
      the donor pool.
AB  - BACKGROUND: We sought to evaluate the effect on short-term outcomes of
      normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs
      for transplantation after cardiac death (DCD). Study parameters included increase
      in number of donors and organs, types of organs procured, and viability of
      kidneys transplanted. METHODS: We retrospectively reviewed medical record data
      for all patients enrolled in our ECMO-supported DCD donor protocol between
      10/1/2000 to 2/01/2004. We also reviewed the records for all patients undergoing
      organ donation after brain-death (DBD) during the study period at our
      institution. Recipient data were obtained and analyzed for all kidneys procured
      from both groups. RESULTS: Twenty patients were enrolled in our DCD protocol and
      underwent attempted organ donation. Fifteen patients completed the protocol; 3
      maintained cardiac function throughout the prescribed 60 minutes after withdrawal
      of life support, and two patients' organs were deemed unsuitable for
      transplantation. Fourteen (70%) of the DCD donor patients originated on the
      trauma service and six (30%) were from other clinical services. The DCD program
      increased the potential donor pool by 33% (61 versus 81 patients) and the number
      of kidneys transplanted by 24% (100 versus 124). A total of 24 kidney, 5 liver,
      and 1 pancreas transplants were performed with these organs. Two of 24 (8.3%) DCD
      kidneys had delayed graft function. There were no perioperative rejection
      episodes or deaths. CONCLUSION: The implementation of a DCD protocol using
      extracorporeal perfusion increased the potential organ donor pool at our
      institution by 33%. This was accomplished without short term adverse effect on
      organ function compared with kidneys transplanted from DBD donors.

PMID- 15995455
TI  - Ionized magnesium in the cerebrospinal fluid of patients with head injuries.
AB  - BACKGROUND: In head injury patients, a decrease in the serum ionized magnesium
      (iMg) concentration is considered to be related to the severity of the injury,
      however, this phenomenon is still not completely understood. The cerebrospinal
      fluid (CSF) iMg concentration has not been well documented under such conditions
      and, moreover, its normal value has not yet been established. We hereby intended
      to investigate the role of the iMg concentration and other parameters in both the
      serum and CSF of head injury patients and identify any relationship with other
      parameters. MATERIALS AND METHODS: The subjects consisted of head injury patients
      without any other serious injuries. Ten healthy volunteers were selected as
      control subjects. Arterial blood and CSF specimens were simultaneously obtained
      and measured. We measured the Glasgow Coma Scale scores (GCS), the intracranial
      pressure (ICP), pH, po2, pco2, sodium, potassium, iCa, iMg, glucose, lactate,
      urea nitrogen. All data are expressed as the mean+/-SD and the units of iMg and
      iCa (corrected under pH 7.40) are given in mmol/L. RESULTS: In the healthy
      subjects, the iMg concentration in the serum/CSF was 0.48 +/- 0.02 / 0.66 +/-
      0.14, and iCa was 1.14 +/- 0.05 / 0.94 +/- 0.07. The GCS of the 15 head injury
      subjects at examination was 8.7 +/- 4.5. When the subjects were divided into 3
      groups according to the GCS level (3 and 4, 5-8, and > or =9) at the time of
      examination, the serum iMg concentration was thus found to be related to the
      severity of injury based on the GCS level (p = 0.028), but not the CSF iMg
      concentration (p = 0.89). No relationship was observed between the iMg
      concentration in the serum and CSF when all specimens were compared, but an
      extremely close correlation was seen in the group with GCS 3 and 4 (p < 0.0001, r
      = 0.995), although no such correlation was seen in the other 2 groups (p = 0.12,
      r = -0.56 in the group with GCS 5-8, and p = 0.26, r = -0.35 in the group with
      GCS > or = 9). There was a significant correlation between the serum iMg and iCa
      (p = 0.0093, r = 0.47), and also between the CSF iMg and iCa concentrations (p <
      0.0001, r = 0.67). CONCLUSION: The serum iMg concentration has been suggested to
      possibly affect the neurologic state through CSF iMg in patients with the most
      severe head injury. In patients with moderate or mild head injuries, however, the
      ionized magnesium concentration is also probably associated with the degree of
      neurologic deficit based on the ionized calcium level. The CSF and serum ionized
      magnesium dissociation may thus result from the slow movement of ionized
      magnesium through the blood brain barrier.

PMID- 15995456
TI  - Improved survival in mice given systemic gene therapy in a gram negative
      pneumonia model.
AB  - BACKGROUND: We previously demonstrated an essential role for lipopolysaccharide
      binding protein (LBP) in the pulmonary immune response to Gram-negative bacterial
      infection. LBP knockout mice had significantly higher mortality, greater rates of
      bacteremia, and higher counts of viable bacteria in their lungs at sacrifice
      compared with wild-type controls. We postulate that systemic LBP gene therapy
      will reconstitute a protective innate immune response in LBP knockout mice and
      that overexpression of LBP in wild-type mice may offer a survival advantage.
      METHODS: 12-16 week old female C57BL/6 wild-type mice and age matched LBP
      knockout mice were given 5 x 10(9) PFU of recombinant adenovirus containing
      either the gene for LBP or the irrelevant control protein beta-galactosidase by
      tail vein injection. 72 hours later each mouse was administered 1 x 10(3) CFU of
      Klebsiella pneumoniae by intratracheal injection. RESULTS: Administration of LBP
      by systemic gene therapy to LBP knockout mice improved survival from Klebsiella
      pneumonia to a level equivalent or better than wild-type mice exposed to the same
      dose of bacteria (36 versus 25%). Wild-type mice given the LBP gene therapy
      demonstrated increased 7 day survival from Klebsiella pneumonia when compared
      with controls treated with beta-galactosidase (68 versus 30%, p = 0.03).
      CONCLUSIONS: Systemic gene therapy with intravenous adenoviral vector transfer of
      LBP significantly improves survival in LBP knockout mice. Overexpression of LBP
      in wild-type mice improves survival from Klebsiella pneumonia. Raising levels of
      LBP in the setting of Gram-negative pneumonia may be of therapeutic benefit.

PMID- 15995457
TI  - Use of near-infrared spectroscopy in early determination of irreversible
      hemorrhagic shock.
AB  - BACKGROUND: In field situations, patient triage may require early determination
      of patients progressing to irreversible shock. We investigated the utility of
      near-infrared spectroscopy (NIRS) in early detection of irreversible hemorrhagic
      shock. METHODS: Twenty instrumented pigs were treated with a protocol involving
      35% blood volume hemorrhage, 90 minutes of shock, and stepwise resuscitation with
      lactated Ringer's. Hemodynamics and NIRS measurements of skeletal muscle (leg),
      stomach, and liver tissue oxyhemoglobin saturation (StO2) were measured at
      baseline, every 30 minutes during shock, and after each resuscitative step.
      Measurements were compared between animals that expired during resuscitation
      (unresuscitatable) and animals that survived all resuscitative steps
      (resuscitatable). RESULTS: Neither global oxygen delivery, oxygen consumption,
      nor lactate distinguished resuscitatable from unresuscitatable animals. Invasive
      measurements of SvO2 did distinguish resuscitatable from unresuscitatable
      animals. After the first fluid bolus, both stomach and leg StO2 differed
      significantly between resuscitatable and unresuscitatable animals. Regression
      analysis revealed skeletal muscle (leg) StO2 obtained after the first
      resuscitative step was a significant mortality predictor despite resuscitation
      (r2=0.45) (p = 0.005). CONCLUSIONS: Non-invasive NIRS monitoring of leg and
      stomach StO2 differentiates resuscitatable from unresuscitatable animals after
      the initial resuscitative bolus. Use of this non-invasive tool may guide
      appropriate use of resuscitative fluids and has possible point-of-care
      applications.

PMID- 15995458
TI  - Intestinal epithelial cells modulate PMN activation and apoptosis following
      bacterial and hypoxic challenges.
AB  - BACKGROUND: The post-ischemic gut may serve to prime and activate neutrophils
      which may lead to the subsequent development of the systemic inflammatory
      response syndrome (SIRS) and multiple organ failure. However, the initiating
      event which may trigger this immunoinflammatory cascade from the gut is unknown.
      Recent studies have indicated that intestinal epithelial cells (IEC) play an
      integral role in generating and transmitting signals between luminal bacteria and
      the host cells in the underlying gut tissues. The purpose of this study was to
      investigate the ability of IEC to modulate PMN responses to bacteria and/or
      hypoxia/reoxygenation (H/R) challenges in vitro. METHODS: Caco2 cell monolayers
      were established in a two-chamber cell culture system. Neutrophils from normal
      human volunteers were placed in the basal chamber and the cell co-culture exposed
      to either apical bacteria (E. coli) and/or H/R challenge. PMN apoptosis, and
      percentage of CD11b expression, superoxide anion production, and elastase release
      were subsequently quantitated. RESULTS: Coculture of PMNs with Caco2 cells led to
      a significant reduction in neutrophil apoptosis in both normoxic and H/R
      conditions. CD11b expression was increased in PMNs exposed to bacteria but the
      greatest expression was noted with PMN cocultured with Caco2 cells and H/R.
      Superoxide anion production was increased in all groups following either H/R or
      bacterial challenge and H/R. Elastase release was highest in neutrophils
      following H/R and exposure to E. coli. CONCLUSION: IEC modulate PMN response to
      bacteria and H/R insults. This results in the production of activated neutrophils
      with an exaggerated lifespan which may promote remote organ failure. Attempts to
      modulate this response may be useful in preventing multiple organ failure
      following severe traumatic shock.

PMID- 15995459
TI  - Challenges for improving trauma care in Japan.

PMID- 15995460
TI  - Follow-up survey of participants attending the Advanced Trauma Operative
      Management (ATOM) Course.
AB  - BACKGROUND: The ATOM Course was developed to educate surgeons about the surgical
      management of penetrating injuries. Its goals are to improve knowledge, self
      confidence, and technical competence. METHODS: ATOM participants completed a 25
      item questionnaire to assess self-efficacy (SE) for advanced trauma operative
      management before and immediately after taking the ATOM course. On follow-up,
      questionnaires were sent to ATOM participants. One was a 7-item survey to assess
      the value of the ATOM course to surgical practice. Another was the 25-item
      questionnaire to assess SE. RESULTS: Four items on the survey to assess the value
      of ATOM had mean scores > or = 4.0 and 3 had mean scores > 3.6. All had modes of
      4.0 or greater. For all items, most respondents selected the agree options
      indicating positive assessments of the ATOM course to their surgical practice.
      For SE, the pre-ATOM mean SE score was 3.88 and the immediate post ATOM mean SE
      score was 4.57 (p < 0.05). The follow-up mean SE score was 4.47 indicating
      maintenance of SE (p > 0.05). CONCLUSIONS: Follow-up data from ATOM participants
      indicate that respondents believe the ATOM course improved their ability to
      identify and repair traumatic injuries. They report they use the techniques and
      knowledge learned in ATOM and confidence remains high after the ATOM course. ATOM
      is well received as an effective teaching strategy for surgical education for the
      management of penetrating injuries.

PMID- 15995461
TI  - Do some U.S. states have higher/lower injury mortality rates than others?
AB  - BACKGROUND: This article examines the hypothesis that the six U.S. states with
      the highest rates of road traffic deaths (group 1 states) also had above-average
      rates of other forms of injury such as falling, poisoning, drowning, fire,
      suffocation, homicide, and suicide, and also for the retail trade and
      construction industries. The converse, second hypothesis, for the six states with
      the lowest rates of road traffic deaths (group 2 states) is also examined.
      RESULTS: Data for these 12 states for the period 1983 to 1995 included nine
      categories of unintentional and four categories of intentional injury. Seventy
      four percent of the group 1 states conformed to the first hypothesis, and 85% of
      the group 2 states conformed to the second hypothesis. CONCLUSION: Group 1 states
      are likely to exhibit above-average rates for most other categories of injury
      death, whereas group 2 states are even more likely to exhibit below-average rates
      for most other categories of injury death.

PMID- 15995462
TI  - Transesophageal echocardiography and therapeutic management of patients
      sustaining blunt aortic injuries.
AB  - BACKGROUND: No objective criteria have been described to help selecting patients
      with major blunt aortic injury (BAI) for postponed surgical repair. The efficacy
      of conservative management of minor BAI needs further evaluation. METHODS: We
      studied 31 patients (Injury Severity Score, 48 +/- 15) who sustained a BAI
      diagnosed using transesophageal echocardiography (TEE). In patients with major
      BAI, the timing of surgery was made on the basis of clinical findings (grade 2)
      or TEE results (grade 3). We retrospectively separated patients into group I
      (rapid surgery, < or = 12 hours; n = 13) and group II (late or no surgery; n =
      11). All major BAIs were confirmed by alternative imaging modalities or surgery.
      Patients with minor BAI (grade 1; n = 7) prospectively underwent conservative
      management with serial TEE follow-up. RESULTS: All patients with grade 3 BAI (n =
      4) were promptly operated on. No group II patient died as a result of aortic
      rupture, and all of them exhibited a small false aneurysm formation (ratio
      between the maximal diameter of the injured aortic isthmus and the diameter of
      the normal descending aorta < 1.4) and hemomediastinum (< 7.2 mm). TEE follow-up
      of group II patients (mean, 5 months) showed stable BAI, whereas follow-up of
      patients with minor BAI (mean, 15 months) disclosed total healing (n = 3) or
      stable lesions (n = 4). CONCLUSION: Conservative management of minor BAI with
      serial follow-up appears to be appropriate. In patients with a grade 2 BAI and
      small false aneurysm formation and hemomediastinum, postponed surgical repair
      appears to be safe. However, these TEE criteria remain to be tested
      prospectively.

PMID- 15995463
TI  - Therapeutic endovascular treatments for traumatic carotid artery injuries.
AB  - OBJECTIVE: The diagnosis and management of traumatic carotid vessel injuries
      continue to be controversial, with direct surgical repair with parent artery
      preservation still presenting difficulties. The purpose of this report is to
      review the endovascular therapy of patients with traumatic carotid vessel
      injuries for preservation of the parent artery, and to determine the safety and
      efficacy of endovascular therapy. METHODS: Ten patients with traumatic carotid
      lesions were treated using therapeutic endovascular methods. Endovascular therapy
      was accomplished by implanting balloons, porous or polytetrafluoroethylene
      covered stents, and/or embolic materials including coils or glue. RESULTS: All
      fistulas and pseudoaneurysms were successfully embolized with no periprocedural
      complications including vessel disruption/rupture, distal embolization, or new
      neurologic deficits. The parent arteries of all patients except one were
      preserved. The reason for the parent artery sacrifice was a thrombus formation
      due to coil migration into the parent artery. No additional surgical procedures
      for vascular lesions were required. There were no delayed neurologic or vascular
      complications, and no lesions recurred during the follow-up periods (mean 20.3
      months). CONCLUSION: The goal of endovascular therapy is the selective
      elimination of the vascular pathology with the normal patency of the cerebral
      arteries. The authors' experience demonstrates that endovascular therapy using
      stents, balloons, and coils is both feasible and safe for treatment of traumatic
      carotid injuries. Of these endovascular methods, the stent can be used to exclude
      the aneurysm or fistula from the circulation and preserve the parent artery in
      selective cases. Long-term follow-up review of these repairs will be necessary to
      provide a full evaluation of the safety and efficacy of these devices.

PMID- 15995464
TI  - Optimal dose of enoxaparin in critically ill trauma and surgical patients.
AB  - BACKGROUND: Low-molecular-weight heparin is effective for prevention of venous
      thromboembolism. The efficacy of daily dosing in critically ill patients is
      unknown. METHODS: Seventeen critically ill patients on 40 mg of enoxaparin
      subcutaneously daily were studied. Anti-Xa activity was measured 4 hours after
      the third dose and before the fourth dose. Adverse events were recorded. RESULTS:
      Mean peak anti-Xa activity was 0.19 +/- 0.09 International Units/mL and mean
      trough was 0.044 +/- 0.04 International Units/mL. The recommended target range is
      0.1 to 0.2 International Units/mL. The trough was below therapeutic levels in all
      but two patients. One thrombosis occurred in a patient despite a therapeutic
      trough. CONCLUSION: Daily dosing of enoxaparin is inadequate for critically ill
      patients and should be abandoned. Further studies using twice daily dosing are
      needed. Patients with renal insufficiency may require an increased interval of
      administration (daily dosing). Anti-Xa levels may not correlate with the risk of
      thromboembolic complications. Patients with renal insufficiency and morbid
      obesity may require alternative dosing and monitoring of anti-Xa levels.

PMID- 15995465
TI  - The high morbidity associated with handlebar injuries in children.
AB  - BACKGROUND: Although injury prevention strategies for bicyclists have focused on
      legislation requiring helmet use to prevent head trauma, direct impact handlebar
      injuries account for a significant proportion of bicycle-related injuries. Little
      attention, however, has been paid to strategies that prevent direct impact
      handlebar injuries. We reviewed our experience with bicycle-related injuries and
      compared outcome for children who flipped over the handlebars to those for
      children who sustained direct impact from the handlebars. METHODS: We queried our
      prospective trauma database for all bicycle injuries from 1998 to 2003. All
      patients with the descriptor "handlebar" in the subtext were selected. Patients
      were divided into two groups: those who flipped over the handlebars (n = 160) and
      those who sustained direct impact from the handlebars (n = 61). We examined age,
      gender, helmet use, injury severity score (ISS), Glasgow Coma Score (GCS), length
      of stay (LOS) and the need for operation. The Student's t test was used to
      compare continuous variables when the data were normally distributed and the Mann
      Whitney was used when the data were skewed. Chi-square analysis or Fisher's exact
      test was used to compare categorical data. RESULTS: There was no difference
      between the two groups with respect to age, gender, helmet use, ISS, and GCS.
      However, children who suffered from handlebar injuries were more likely to
      require operative intervention (19/61 versus 28/160, p = 0.04) and had a
      significantly longer LOS (3 days versus 1 day, p < 0.001). Children who sustained
      direct impact from the handlebars and required operative intervention were
      statistically more likely to suffer from abdominal or soft tissue injuries, while
      those who flipped over the handlebars were statistically more likely to suffer
      from facial or skeletal injuries. CONCLUSIONS: Children who suffer from direct
      impact of the handlebars are more likely to require operative intervention and
      have a longer LOS than those who flip over the handlebars. While helmet
      utilization by bicyclists may have reduced the number of serious head injuries,
      direct impact from the handlebars remains a major source of bicycle-related
      morbidity since nearly one third of these patients required surgery. Future
      injury prevention strategies for bicyclists should be aimed at reducing the
      incidence of direct impact handlebar-related injuries.

PMID- 15995466
TI  - Does the presence of an upper extremity injury affect outcomes after major
      trauma?
AB  - BACKGROUND: There is a paucity of information about the impact of upper extremity
      (UE) injuries on patient outcomes, particularly after major trauma. METHODS: Data
      were obtained from a statewide trauma registry. Cases were defined as major
      trauma cases (Injury Severity Score > 15) with (UE group) and without (no-UE
      group) an associated upper extremity injury. Multivariate analysis was performed
      to identify independent predictors of outcome. RESULTS: Major trauma patients
      with UE injury were 1.5 times (p = 0.011) more likely than the no-UE group to
      have a length of stay greater than 7 days. After adjusting for age, mechanism of
      injury, and Injury Severity Score, UE injury was not an independent predictor of
      discharge destination. CONCLUSION: In major trauma patients, the presence of an
      upper extremity injury is a significant predictor of length of stay, indicating a
      greater complexity and cost of care associated with this group of major trauma
      patients.

PMID- 15995467
TI  - Should plain X-rays be routinely performed after blunt knee trauma? A prospective
      analysis.
AB  - BACKGROUND: We tested the hypothesis that it was possible to decrease the number
      of performed x-rays after a knee trauma without delayed fracture diagnosis by
      using the Ottawa knee rules. METHODS: Patients had routine x-rays of the injured
      knee during the first stage of the study and selective x-rays during the second
      stage. All patients were followed up to 6 months after the trauma. RESULTS: 138
      patients were included in the first stage; 57 had negative Ottawa criteria: no
      fracture was observed; following the Ottawa rules, 41% of the x-rays could have
      been avoided. 178 patients were included in the second stage; 63 patients had
      negative Ottawa criteria: no fracture was diagnosed during the whole follow-up;
      35% of the x-rays have been avoided. CONCLUSIONS: Ottawa rules allowed decreasing
      the number of x-rays performed after a knee trauma by 35% with a sensitivity for
      a knee fracture detection of 100%.

PMID- 15995468
TI  - Cervical spine assessment in the unconscious trauma patient: a major trauma
      service's experience with passive flexion-extension radiography.
AB  - BACKGROUND: There is no consensus on the most appropriate method of cervical
      spine assessment in unconscious trauma patients. Passive flexion-extension
      imaging is one option for further investigating unconscious patients whose plain
      cervical radiographs are normal. This study examines the usefulness of this
      passive imaging in investigating for occult cervical injury. METHODS: All
      unconscious patients admitted to The Alfred Trauma Intensive Care Unit over 1
      year (January 1-December 31, 1998), who could not be clinically assessed within
      48 hours in regard to their cervical spine, were identified. Results of passive
      flexion-extension radiography were compared with final injury status and clinical
      outcome as determined by retrospective review of the imaging reports,
      radiographic films, and case notes. RESULTS: One hundred twenty-three patients
      with normal three-view plain radiographs proceeded to passive functional
      investigation. These were false-negative in four of the seven patients with
      cervical spine injuries at presentation. No patients suffered any adverse
      neurologic events from their delayed diagnoses or from the flexion-extension
      procedure. CONCLUSION: Passive flexion-extension imaging has inadequate
      sensitivity for detecting occult cervical spine injuries. Although no patients
      suffered adverse neurologic complications, the potential for devastating
      consequences from missed cervical injury has resulted in the removal of passive
      flexion-extension imaging from the screening protocol.

PMID- 15995469
TI  - Incidence and severity of biceps long head tendon lesion in patients with
      complete rotator cuff tears.
AB  - BACKGROUND: Biceps long head tendon lesion is commonly associated with rotator
      cuff tendon pathology. This study is to determine the pathologic spectrum of
      biceps long head tendon in surgical cases with complete full thickness rotator
      cuff tear. METHODS: Between 1993 and 2002, 122 complete rotator cuff tears with
      surgery were included for the analysis. During surgery, biceps long head tendon
      was grossly examined or evaluated via arthroscopy. A simplified classification
      was used to describe the biceps lesion. RESULTS: 50 (41%) patients had type 1
      lesion (tendinitis), 10 (8%) patients had type 2 lesion (subluxation), 12 (10%)
      patients had type 3 (dislocation), 15 (12%) patients had type 4 (partial tear),
      and 6 patients (5%) had type 5 (complete rupture). The remaining 29 patients
      (24%) did not have obvious pathology. All chronic rotator cuff tear (> 3 months)
      were associated with biceps tendon pathology. A rotator cuff tear greater than 5
      cm as determined at surgery was strongly associated with an advanced biceps
      lesion. CONCLUSION: Biceps tendon injuries are associated with complete rotator
      cuff tears and there may be a causal relationship due to the impingement that
      occurs. Early identification and repair of rotator cuff lesions may prevent
      further deterioration of the biceps tendon.

PMID- 15995470
TI  - Locked plate fixation and intramedullary nailing for proximal humerus fractures:
      a biomechanical evaluation.
AB  - BACKGROUND: Internal fixation of proximal humeral fractures is associated with a
      considerable secondary malalignment rate. Fixed-angle implants have been
      suggested to increase the stability of fixation. METHODS: The biomechanical
      properties of four different implants were tested. These included an internal
      fixator with semi-elastic properties (reference), the Synthes T-plate, a locked
      plate with rigid properties and a spiral blade locked intramedullary nail (PHN).
      These implants were assessed in twenty-four osteotomized pairs of human cadaveric
      humeri. Specimens were subjected to two-hundred cycles of axial loading and
      torque followed by load to failure. RESULTS: The PHN had greater axial stiffness
      than the reference and the T-plate. During torque, all implants were stiffer than
      the reference. During cyclic loading, there were no differences between the T
      plate and the reference. Both the rigid internal fixator and the PHN had less
      irreversible deformation than the reference. Both implants resisted higher loads
      before failure. CONCLUSION: This study showed that the proximal humeral nail and
      the rigid internal fixator are stronger than the semi-elastic locked plate and
      the Synthes T-plate for unstable subcapital proximal humeral fractures.

PMID- 15995471
TI  - Subsequent displacement of initially nondisplaced and minimally displaced
      fractures of the lateral humeral condyle in children.
AB  - BACKGROUND: Although conservative treatment is a well-established method for
      treating nondisplaced and minimally displaced (< or =2 mm) fractures of the
      lateral humeral condyle in children, there is still great uncertainty concerning
      the rate and time course of subsequent displacement. Therefore, the appropriate
      frequency of radiographic follow-up remains unclear. The aim of the study was to
      determine the rate of subsequent displacement after conservative treatment of
      nondisplaced and minimally displaced fractures of the lateral humeral condyle in
      children. METHODS: A retrospective analysis of 51 consecutive patients with
      nondisplaced and minimally displaced fractures of the lateral humeral condyle was
      performed. RESULTS: Five fractures (9.8%) displaced within 5 days while
      immobilized and were safely detected by a follow-up radiograph within 1 week
      after trauma. Additional follow-up radiographs between the first and third weeks
      did not show relevant alterations in the fracture gap. Mean time of cast
      immobilization was 22 days, with a range of 17 to 34 days. No pseudarthrosis
      occurred. CONCLUSION: Fractures with less than or equal to 2 mm of displacement
      can probably be primarily treated safely by cast immobilization. Anteroposterior
      and lateral radiographs out of plaster between the fourth and sixth days are
      necessary to diagnose subsequent displacement of unstable fractures, whereas
      further "late" displacement did not occur.

PMID- 15995472
TI  - Teleconsultation with the mobile camera-phone in remote evaluation of
      replantation potential.
AB  - BACKGROUND: The purpose of the present study was to investigate the feasibility
      of teleconsultation with the mobile camera-phone to transfer clinical images and
      communicate on line for evaluation of replantation potential in completely
      amputated fingers. METHODS: Teleconsultations including clinical images of the
      amputated portion and stump as well as patient information were transmitted
      between the physicians in the emergency room and the consultant phlstic surgeon
      through Panasonic camera-phones, which had a built-in 110,000-pixel digital
      camera and a 65,536 colors display. The digital images displayed on the screen
      were further evaluated by three remote plastic surgeons individually and the
      evaluations were compared with the decision made according to onsite inspection
      by the consultant surgeon. RESULTS: The study population consisted of 35 patients
      with a total of 60 digital injures occurring between January to October 2003. The
      ability to identify the amputation location and status of amputation kwel from
      remote diagnosis was demonstrated by all three surgeons in 90% and 87% of these
      sixty amputated digits respectively. Of the 42 digits that were considered to
      have replantation potential during onsite evaluation, 38 (90%) digits were
      considered to be so by all three surgeons in group agreement during remote
      diagnosis. Of the 18 digits that were not considered to be replantable during
      onsite evaluation, 15 (83%) digits were also deemed without replantation
      potential, thus making the sensitivity and specificity of recognizing digital
      replantation potential, 90% and 83_'O re,_1pectively. CONCLUSIONS: The camera
      phone is a feasible tool for remote evaluation regarding the replantation
      potential of completely amputated fingers and it holds significant promise in
      avoiding unnecessary patient transfer by providing useful information.

PMID- 15995473
TI  - Reconstruction with distraction osteogenesis for juxta-articular nonunions with
      bone loss.
AB  - BACKGROUND: Nonunions of a juxta-articular lesion with bone loss, which represent
      a challenging therapeutic problem, were treated using external fixation and
      distraction osteogenesis. METHODS: Seven juxta-articular nonunions (five septic
      and two aseptic) were treated. The location of the nonunion was the distal femur
      in four patients, the proximal tibia in one patient, and the distal tibia in two
      patients. All of them were located within 5 cm from the affected joints.
      Preoperative limb shortening was present in six cases, averaging 2.9 cm (range, 1
      7 cm). The reconstructive procedure consisted of refreshment of the nonunion
      site, deformity correction, stabilization by external fixation, and lengthening
      to eliminate leg length discrepancy or to fill the defect. Shortening-distraction
      was applied to six patients and bone transport to one patient for reconstruction.
      Intramedullary nailing to reduce the duration of external fixation was
      simultaneously performed in two cases. All the patients had at least 1 year of
      follow-up evaluation. RESULTS: Osseous union without angular deformity or leg
      length discrepancy greater than 1 cm was achieved in all patients. The mean
      amount of lengthening was 5.8 cm (range, 2.2-10.0 cm). The mean external fixation
      period was 219 days (range, 98-317 days), and the mean external fixation index
      was 34.4 days/cm (range, 24.5-47.6 days/cm). All patients reported excellent pain
      reduction. There were no recurrences of infection in five patients with prior
      history of osteomyelitis. The functional results were categorized as excellent in
      two, good in three, and fair in two. CONCLUSION: Despite the length of
      postoperative external fixation, distraction osteogenesis can be a valuable
      alternative for the treatment of juxta-articular nonunions.

PMID- 15995475
TI  - Early administration of hyperbaric oxygen therapy in distraction osteogenesis--a
      quantitative study in New Zealand rabbits.
AB  - BACKGROUND: We investigated the effect of hyperbaric oxygen (HBO) therapy on the
      early phase of tibial lengthening in our established rabbit model. METHODS:
      Twenty-four male rabbits (six per group) underwent right tibial lengthening by 5
      mm. Group 1 then underwent 2.5 atmospheres of absolute hyperbaric oxygenation for
      2 hours daily for 6 weeks postoperatively; group 2, for early 5 weeks (weeks 1
      5), group 3, for late 5 weeks (weeks 2-6), and group 4 had no HBO therapy. Bone
      mineral density (BMD) was measured before surgery and weekly thereafter from
      weeks 2 through 6. The mechanical strengths of the lengthened tibias were
      measured. RESULTS: Significantly higher mean %BMDs were obtained for groups 1 and
      2 compared with groups 3 and 4. There was no difference in the mean %BMD between
      groups 1 and 2 (p > 0.05). The results were similar for mean percentage maximal
      torque; group 1 had the maximum torque, followed sequentially by groups 2 though
      4. CONCLUSION: The study results suggest that early and full-term administration
      of HBO therapy on tibial lengthening may achieve better benefits.

PMID- 15995474
TI  - Fracture hematoma is a potent proinflammatory mediator of neutrophil function.
AB  - BACKGROUND: Patients with multiple skeletal injuries are susceptible to acute
      respiratory distress syndrome and multiple organ failure, which result from
      hyperactivation of the immune system. This study was designed to evaluate in
      vitro the proinflammatory properties of fracture hematoma (FH). METHODS: FH was
      isolated from patients undergoing emergent open reduction and internal fixation
      for isolated closed fractures. Neutrophils (PMNs), isolated from healthy
      volunteers, were exposed to the FH supernatant and activation was examined (CD11b
      and CD18 adhesion receptor expression and respiratory burst). PMN phagocytosis,
      apoptosis, and transmigration across an endothelial barrier were also assessed.
      RESULTS: FH increased PMN respiratory burst (control, 100; FH-treated, 186) and
      phagocytosis (control, 100; FH-treated, 172) but had no effect on adhesion
      receptor expression. Transendothelial migration of PMNs was unaffected, although
      FH was toxic to endothelial cells. In contrast, apoptosis of FH-treated PMNs was
      delayed (control, 46; FH-treated, 8). CONCLUSION: These effects, although
      beneficial at the site of injury in the context of antibactericidal function, may
      cause PMN-mediated tissue injury systemically.

PMID- 15995476
TI  - Influence of personal armor on distribution of entry wounds: lessons learned from
      urban-setting warfare fatalities.
AB  - BACKGROUND: This study was undertaken to examine the distribution of entry wounds
      resulting from firearms and shrapnel in soldiers wearing military personal armor
      systems (MPAS) in low-intensity urban combat conditions. METHODS: Data were
      collected for a retrospective analysis on all combat fatalities sustained by the
      Israeli Defense Force (IDF) between March 30, 2002, and April 22, 2002, during
      Defensive Shield Operation in the West Bank. Twenty-six of the 30 fatalities were
      evaluated in the Israeli National Center of Forensic Medicine. RESULTS: A total
      of 149 entrance wounds were divided into shrapnel and bullet groups. The "face
      neck" region had the highest density rate compared with other body regions in
      both shrapnel and bullet groups (2.97 and 2.41, respectively; p < 0.0001). In
      both groups, the overall prevalence of anterior injuries was significantly higher
      than posterior ones (78.9% vs. 21.1% in the shrapnel group and 68.5% vs. 31.5% in
      the bullet group, p < 0.001). However, anterior and posterior chest injuries had
      a reverse yet more even distribution (43.8% and 56.2% in the bullet group and 40%
      and 60% in the shrapnel group, respectively; p < 0.001). The difference in the
      average diameters of entry wounds in the covered versus uncovered regions (0.79
      +/- 0.42 cm vs. 0.73 +/- 0.29 cm, respectively) was not statistically significant
      (p = 0.11). CONCLUSION: The use of MPAS turned the face-neck region into the most
      vulnerable body part, as shown by its prominent density rate, especially in the
      shrapnel group. MPAS designed for urban setting warfare should provide maximal
      shielding both to the anterior and posterior chest regions. The diameter of
      entrance wounds in the covered versus the uncovered areas was not statistically
      significant, suggesting that only a minor deformation of the bullet takes place
      while traversing the Kevlar vest.

PMID- 15995477
TI  - Modeling the effect of non-penetrating ballistic impact as a means of detecting
      behind armor blunt trauma.
AB  - BACKGROUND: According to the National Institute of Justice (NIJ) Standard
      0101.04, the maximum deformation a soft armor vest can undergo without
      penetration is 44 mm. However, this does not take into account the effect of the
      pressure wave or energy transferred to the organs within the torso due to behind
      armor blunt trauma (BABT). Therefore, a study was undertaken to develop a finite
      element model (FEM) to study these effects. METHODS: A finite element model (FEM)
      of the human thorax; complete with musculoskeletal structure and internal organs
      (heart, liver, lungs and stomach), intercostal muscle and skin, has been
      developed in LS-DYNA. A Kevlar vest was modeled on the chest to simulate non
      penetrating ballistic impact. RESULTS: Using a projectile modeled with a size and
      mass equivalent to a 9 mm (124 grain) bullet at 360 and 425 m/s, four impacts
      were simulated against NIJ Level II and Level IIIa Kevlar vests at the midsternum
      and right thorax. At the same velocity, the pressures decreased by a factor of 3
      and the energy absorbed by the organs decreased by a factor of 6 for the NIJ
      Level II and Level IIIa vests, respectively. As the projectile velocity
      increased, the peak pressures increased by a factor of 3 while the energy
      absorbed by the organs increased by a factor of 4. CONCLUSIONS: The resulting
      pressure profiles and kinetic energy exhibited by the respective organs indicate
      this model may be useful in identifying mechanisms of injury as well as organs at
      an elevated injury risk as a result of BABT.

PMID- 15995478
TI  - Protective effect of erythropoietin on type II pneumocyte cells after traumatic
      brain injury in rats.
AB  - BACKGROUND: The main objective was to evaluate the protective effect of
      erythropoietin on lung ultrastructure against damage in rats after traumatic
      brain injury. METHODS: We used forty Wistar-Albino female rats weighing 170-200
      gr. The rats were allocated into five groups. The first group was the control and
      the second was the craniotomy without trauma. The third group was the trauma
      group. The fourth and fifth groups were erythropoietin (1000 IU/kg) and vehicle
      (0.4 mL/rat) groups, respectively. A weight-drop method was used for achieving
      head trauma. Samples were obtained from pulmonary lobes 24-hour post injury.
      Lipid peroxidation levels were determined and electron microscopic scoring model
      was used to reveal the ultrastructural changes. RESULTS: Ultrastructural
      evaluation revealed pathologic changes in the trauma group compared with the
      control group (p < 0.05). Lipid peroxidation levels were found to be higher in
      the trauma group (p < 0.05). Erythropoietin significantly reduced both the
      ultrastructural pathologic changes and the lipid peroxidation levels in the
      treatment group (p < 0.05). CONCLUSIONS: Erythropoietin protects the
      ultrastructure of pneumocyte type II cells against damage after traumatic brain
      injury.

PMID- 15995479
TI  - Escharotomy using an enzymatic debridement agent for treating experimental burn
      induced compartment syndrome in an animal model.
AB  - BACKGROUND: In patients with deep circumferential burns, adequate resolution of
      burn-induced compartment syndrome (BICS) is achieved by surgical escharotomy.
      Surgical escharotomy is traumatic, may cause considerable blood loss, does
      nothing toward debridement of the burn wound, and entails possible morbidity and
      complications. Debridase is a Bromelain derived enzymatic preparation capable of
      lysing the burn eschar within 4 hours, obviating the need for surgical
      debridement. It has an affinity to burned necrotic tissue and does not damage
      healthy skin. In our clinical assessment of the Debridase efficacy, we found in
      several cases of deep burns of the limbs that the measured IC pressure subsided
      after 2-4 hours of Debridase application and none of the enzymatic escharotomy
      treated patients suffering from circumferential burns developed BICS. To confirm
      these observations we conducted this controlled study. AIM: to assess the
      efficacy of Debridase for treating BICS in an animal model. MATERIALS AND
      METHODS: A model for BICS was developed by making circumferential burns to pig
      legs and monitoring the anterior compartment the legs. BICS was induced in the
      legs of 5 pigs, 20 legs. 10 legs were treated with Debridase and 10 served as
      nontreated controls, treated by surgical escharotomy at the conclusion of the
      experiment. RESULTS: Debridase reduced BICS within 30 minutes from application.
      Debridase was as effective as a standard surgical escharotomy. CONCLUSION:
      Escharectomy using an effective enzymatic debriding agent is potentially an
      adequate, simple, fast and effective procedure to treat BICS, it has the added
      benefit of burn debridement without surgical escharotomy.

PMID- 15995480
TI  - Evaluating trauma center quality: does the choice of the severity-adjustment
      model make a difference?
AB  - CONTEXT: The Major Trauma Outcome Study (MTOS) database was created by the
      American College of Surgeons over 20 years ago to establish national norms for
      trauma care. The primary trauma outcome prediction models used for evaluating the
      quality of trauma care, TRISS and ASCOT (A Severity Characterization of Trauma),
      were developed using the MTOS database. OBJECTIVE: First, to determine whether
      TRISS and ASCOT agree on hospital quality. Second, to determine whether TRISS and
      ASCOT accurately reflect contemporary outcomes in trauma care. DESIGN, SETTING
      AND PATIENTS: A retrospective cohort study based on 91,112 patients admitted to
      69 hospitals between 2000 and 2001 in the National Trauma Databank. Using TRISS
      and ASCOT, the ratio of the observed to expected mortality rate (O/E ratio) was
      calculated for each hospital. Hospitals whose O/E ratio was statistically
      different from 1 were identified as quality outliers. Kappa analysis was used to
      assess the degree to which TRISS and ASCOT agreed on the identity of hospital
      quality outliers. RESULTS: TRISS and ASCOT disagreed on the outlier status of 35
      of the 69 hospitals. Kappa analysis revealed only fair agreement (kappa = 0.23; p
      = 0.0015) between TRISS and ASCOT in identifying quality outliers. Thirty-eight
      hospitals were identified by the TRISS method as high-performance hospitals.
      CONCLUSION: First, TRISS and ASCOT exhibit substantial disagreement on the
      identity of quality outliers within the NTDB. Second, an unrealistically high
      number of hospitals were identified as high-performance outliers using either
      TRISS or ASCOT. These findings have important implications for the use of TRISS
      and ASCOT for benchmarking performance and quality improvement.

PMID- 15995481
TI  - M-study; arguments for regional trauma databases.
AB  - BACKGROUND: The TRISS methodology, in combination with coefficients derived from
      the Major Trauma Outcome Study (MTOS), is the most widely used outcome prediction
      model for the care of trauma patients. Utilizing the M-statistic, different
      populations of trauma patients can be compared with the population originally
      enrolled in the MTOS. PURPOSE: We hypothesized that databases outside of North
      America would not be well matched to the MTOS study and thus the TRISS
      methodology would not accurately predict outcome in these different populations.
      METHODS: All trauma studies utilizing TRISS methodology that were published
      between 1990-2003 were reviewed and M-statistics calculated based on the
      population described in the study. The populations were grouped by the following
      geographic locations: Europe, Asia/Africa and North-America. RESULTS: The median
      M-statistic for Europe was 0.65, compared with 0.88 for Asian/African databases,
      and 0.90 for North-American studies. There was a significant difference between
      European and North-American studies (p < 0.05). CONCLUSION: The trauma
      populations described in European studies differ significantly from the MTOS with
      respect to injury severity match, indicating the need for the development of
      regional trauma databases and modified TRISS coefficients based on the geographic
      location of the injured population included.

PMID- 15995483
TI  - Operative management of liver rupture with combined central bile duct injury in
      pediatric patients.

PMID- 15995484
TI  - Traumatic aortic pseudoaneurysm after airbag deployment: successful treatment
      with endoluminal stent-graft placement and subclavian-to-carotid transposition.

PMID- 15995485
TI  - An unusually favorable outcome of bilateral vertebral arterial dissections: case
      report and review of the literature.

PMID- 15995486
TI  - An unusual case of impalement of the cranium in a child.

PMID- 15995487
TI  - Pumpless extracorporeal lung assist (pECLA) in patients with acute respiratory
      distress syndrome and severe brain injury.
AB  - BACKGROUND: A retrospective analysis was performed to estimate the practicability
      of a pumpless extracorporeal lung assist system (pECLA) in trauma patients
      suffering from severe brain injury and the acute respiratory distress syndrome
      (ARDS). METHODS: Five patients with acute severe brain injury and ARDS,
      ventilated in a lung protective mode, were connected to pECLA to avoid the
      detrimental effects of hypercapnia on intracranial pressure (ICP) and cerebral
      outcome. With pECLA hypercapnia was eliminated in all patients while the minute
      volume of artificial ventilation could be reduced. Subsequently, ICP was reduced,
      systemic hemodynamics and cerebral perfusion pressure remained stable. One
      patient died due to multi-organ failure as a consequence of multi-trauma. The
      remaining patients survived showing a good neurologic function. CONCLUSIONS:
      pECLA is a promising alternative compared with conventional pump-driven systems
      for patients with ARDS and brain injury, since the pECLA system has minor
      restrictions, limitations and side effects.

PMID- 15995488
TI  - Use of recombinant activated factor VII to treat the acquired coagulopathy of
      trauma.
AB  - Recombinant activated factor VII (rFVIIa) is a drug commonly utilized in the
      treatment of patients with hemophilia and inhibitors. However, its use in
      previously normal patients with an acquired coagulopathy after trauma and surgery
      is increasing. Multiple trauma case reports and several case series are
      available, lending support for the efficacy of the drug in reversing the
      coagulopathy of trauma. Data from six large animal studies evaluating the
      efficacy in trauma models are available for evaluation. A single prospective
      randomized study in elective surgery has recently been published, documenting
      reduced blood loss and decreased transfusion after a single preoperative dose.
      This review describes those studies and reiterates the need for well designed
      prospective randomized human trauma studies.

PMID- 15995489
TI  - Splenic and pancreatic infarction due to motorcycle handlebar injury.

PMID- 15995491
TI  - The utility of clinical and laboratory data for predicting intraabdominal injury
      among children.

PMID- 15995492
TI  - A true triceps-splitting approach for treatment of distal humerus fractures: a
      preliminary report.

PMID- 15995493
TI  - A case of severe lactic acidosis associated with extreme mental stress.

PMID- 15995498
TI  - Frequency map variations in squirrel monkey primary auditory cortex.
AB  - OBJECTIVE: The goal of this work is to understand the neural basis for cortical
      representation of hearing in highly vocal primates to gain insights into the
      substrates for communication. Variation patterns in frequency representation
      among animals are incorporated into an explanatory model to reconcile
      heterogeneous observations. STUDY DESIGN: Prospective. METHODS: Thirty-four
      squirrel monkeys underwent microelectrode mapping experiments in primary auditory
      cortex (AI) using tone pip stimuli. Characteristic frequency (CF) was extracted
      from the excitatory frequency receptive field. Frequency maps were reconstructed
      using Voronoi-Dirichlet tessellation. The spatial locations (rostral vs. caudal)
      of highest CF isofrequency contours (minimum length 1 mm) and highest CF neuronal
      clusters on the temporal gyral surface were analyzed. RESULTS: Isofrequency
      contours at least 1 mm long with CFs greater than 2.9 kHz (75% cases) are
      accessible on the temporal gyrus. Variability of the highest CF isofrequency
      contours accessible on the temporal gyrus has an interquartile range from 2.9 to
      5.1 (mean 4.3) kHz. The highest CF isofrequency contours are located mainly in
      rostral AI, whereas the highest CF neuronal clusters flanking fully expressed
      isofrequency contours are equally distributed in rostral and caudal locations.
      CONCLUSIONS: Squirrel monkey AI frequency map variations are sizeable across
      animals and small within single animals (interhemispheric comparison). AI
      frequency map variations, modeled as translations and rotations relative to the
      lateral sulcus, are independent transfers. Caution must be exercised when
      interpreting nominal frequency map changes that are attributed to hearing loss
      and auditory learning effects.

PMID- 15995499
TI  - Changing impact of gastroesophageal reflux in medical and otolaryngology
      practice.
AB  - OBJECTIVES/HYPOTHESIS: A major trend in gastroesophageal reflux disease (GERD) is
      an observed increased prevalence of the problem, with an associated burden on
      health care resources. There are relatively few objective reports of increasing
      prevalence of this disease, and there are no epidemiologic reports that discuss
      changing practice strategies in managing the disease. The clinical problem is of
      critical importance to practicing otolaryngologists, who manage the impact of
      GERD on diseases affecting the ear, nose, and throat. The hypothesis of this
      thesis is that 1) GERD is an increasing problem affecting outpatient office
      visits over time, and 2) the disease is increasingly managed with prescription
      pharmacotherapy. STUDY DESIGN: Retrospective national medical database review
      using the National Ambulatory Medical Care Survey. METHODS: Twelve years of data
      (1990-2001) were examined with visits weighted to provide U.S. estimates of care.
      Average annual frequencies and visit rates were calculated for total visits and
      by age, sex, race, and physician specialty. Selected issues in GERD treatment
      were also examined, including prescriptions and physician/patient counseling
      regarding stress management, tobacco abuse, and diet modification. Trends were
      reported based on changes in care across three time periods to satisfy
      statistical significance: 1990 to 1993, 1994 to 1997, and 1998 to 2001. RESULTS:
      Between 1990 and 1993 and 1998 and 2001, there was a significant increase in U.S.
      ambulatory care visits for GERD, from a rate of 1.7 per 100 to 4.7 per 100. There
      were no significant changes in race, although there was a small trend toward
      increased GERD visits in the age group over 44 years old and in the male sex.
      Office visits to otolaryngologists increased from 89,000 to 421,000 between the
      time periods of 1990 to 1993 and 1998 to 2001. This also represented a percent
      increase in office encounters by otolaryngologists compared with visits by all
      specialties from 2.9% to 4.4%. Over the three time periods, there was a fall in
      prescriptions for histamine (H2) blockers from 58.1% to 20.7% of total
      prescriptions. Over the same three time periods, prescriptions of proton pump
      inhibitors increased from 13.2% to 64.6%. Physician recommendations for over the
      counter medications fell from 18.8% to 6.6%. Average annual counseling during
      ambulatory care visits for GERD was assessed for the period from 1998 to 2001 as
      follows: diet counseling was provided at 27.2% of encounters, tobacco cessation
      counseling was provided at 3.9%, and stress management was discussed at 3.9%.
      CONCLUSIONS: During the 1990s, there was a substantial increase in the use of
      ambulatory care services for GERD. Although much of this increase was among the
      primary care community, otolaryngologists appeared to have an increasingly
      prominent role in the management of this disease. There have also been dramatic
      changes in physician prescribing patterns for GERD, with the emergence of the
      predominant role of proton pump inhibitors. However, the use of physician
      counseling for lifestyle modification of factors known to affect GERD remains
      very low. The increasing impact of GERD on physician practice emphasizes the
      importance of both physician and patient education in the delivery of health care
      related to this disease.

PMID- 15995500
TI  - Development and immunophenotyping of squamous cell carcinoma xenografts: tools
      for translational immunology.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this study were to delineate methods for
      the development of primary squamous cell carcinoma (SCCHN) xenografts and to
      define human leukocyte antigen (HLA), melanoma-associated antigen (MAGE)-A3, and
      human papilloma virus (HPV) 16 antigenic expression in resultant cellular
      products. STUDY DESIGN: Prospective experimental model. METHODS: Freshly isolated
      SCCHN xenografts were established in nonobese diabetic/severe combined
      immunodeficiency (NOD/SCID) mice using a variety of methods. Resultant tumors
      were analyzed for expression patterns of HLA-A, MAGE-A3, and HPV 16. Appropriate
      controls were included to ensure the presence of human RNA. RESULTS: Three
      xenografts were successfully established and passaged in vivo. Characterization
      of the resultant products revealed that one was positive for HLA-A2 at both the
      DNA and protein levels. One of the tumor lines expressed MAGE-A3, whereas none
      expressed HPV 16. CONCLUSIONS: Freshly isolated SCCHN can be used to generate
      primary xenografts. Characterization of select patterns of protein expression in
      established xenografts is a precursor to the development of a mouse model for
      SCCHN using tumor bearing animals reconstituted with autologous patient
      leukocytes.

PMID- 15995501
TI  - Fatal apnea in piglets by way of laryngeal chemoreflex: postmortem findings as
      anatomic correlates of sudden infant death syndrome in the human infant.
AB  - OBJECTIVES/HYPOTHESIS: Intrathoracic petechiae are a prominent diagnostic finding
      in sudden infant death syndrome (SIDS) victims. In this study, the laryngeal
      chemoreflex (LCR) was elicited experimentally to discover whether intrathoracic
      petechiae would be produced by way of the LCR. The hypothesis was that water
      stimulation of the larynx in piglets, leading to death by prolonged apnea, would
      produce postmortem findings similar to those found in SIDS victims. STUDY DESIGN:
      Using the piglet as an animal model, the LCR was initiated by way of water
      stimulation of the larynx, resulting in death. Normoxic and hypoxic conditions
      were established before the stimulation. The piglets were studied postmortem to
      determine the relationship between the physiologic mechanisms of the LCR and
      characteristic pathologic findings in SIDS. METHODS: Using protocols approved by
      animal care, 14 mixed-breed piglets aged 7 to 14 days were sedated with a
      ketamine/xylazine mixture. Respiratory and pressure-monitoring devices were
      affixed and light anesthesia maintained with Surital infusion. In 10 of the
      piglets, a small catheter was placed between the arytenoid cartilages, and 5 mL
      of tap water was introduced over 1 second. The LCR ensued, producing periods of
      central apnea bordered by gasping efforts and resulting in hypoxemia and death in
      all cases. Four piglets underwent this manipulation in normoxic conditions. Six
      breathed a hypoxic gas mixture for 1 hour to bring their Po2 down to below 50
      torr before water was introduced into the larynx. Four control piglets breathed
      the hypoxic gas mixture for 1 hour (without water stimulation or LCR) before
      Surital overdose. Within 24 hours of death, all piglets underwent
      thoracoabdominal autopsy by a blinded evaluator experienced in SIDS pathology.
      RESULTS: The autopsies revealed nothing remarkable in the abdominal viscera of
      any of the experimental animals. Thymus, heart, and lungs were graded 0 to 4 to
      indicate the degree of petechiae on external surfaces. Average cumulative scores
      (ACS) were applied to each animal. The control (hypoxic) piglets had no petechiae
      (ACS 0.0). The normoxic experimental piglets had moderate petechiae (ACS 3.5).
      The hypoxic experimental piglets had more prominent petechiae (ACS 6.3).
      CONCLUSIONS: Stimulation of the LCR, leading to death by prolonged apnea,
      produces postmortem findings in piglets similar to those found in SIDS victims.
      Petechiae were more severe among piglets pretreated with a hypoxic mixture of
      gases. This study supports the hypothesis that initiation of the LCR may produce
      pathologic features often prominent in SIDS.

PMID- 15995502
TI  - Bone regeneration in cranial defects previously treated with radiation.
AB  - OBJECTIVES/HYPOTHESIS: Bone reconstruction in the head and neck region is
      frequently performed in the context of previous radiation treatment. Thus, the
      effectiveness of tissue engineering approaches for regenerating bone in radiated
      defects needs to be determined before considering application to patients.
      Incomplete healing is described when using osteoinductive protein therapy alone
      for bone defects previously treated with radiation. We hypothesized that a
      different approach using ex vivo gene therapy can heal these severely compromised
      defects. STUDY DESIGN: Animal study using Fisher rats. METHODS: Two weeks before
      surgery, rats received either no radiation or a 12 Gray radiation dose to the
      calvarium. Syngeneic dermal fibroblasts were transduced ex vivo using an
      adenoviral vector containing the cDNA for bone morphogenetic protein (BMP)-7.
      Critical-sized calvarial defects were created, and either a transduced cell
      seeded scaffold or an autologous bone graft was placed into the defect.
      Nonradiated defects were harvested 4 weeks later for both groups. Radiated
      defects treated with bone grafts were harvested at 4 weeks, and those treated
      with gene therapy were harvested either at 4 or 8 weeks. Gross inspection and
      histology were used to evaluate wound healing. RESULTS: None of the bone grafts
      had gross or histologic evidence of healing at the wound margins. The nonradiated
      gene therapy treated defects revealed gross and histologic near-100% bone
      regeneration by 4 weeks after surgery. By gross inspection, the radiated defects
      had soft tissue admixed with islands of bone at both 4 and 8 weeks. The
      histologic appearance revealed areas of dense bone in a nonconfluent pattern
      admixed with adjacent cells having the morphologic appearance of hypertrophic
      chondrocytes, suggesting continued endochondral ossification. CONCLUSIONS:
      Preoperative radiation significantly impairs the ability of BMP-7 ex vivo gene
      therapy to heal rat critical-sized cranial defects. This finding has significant
      implications for translating this tissue engineering approach to patients with
      cancer-related segmental bone defects.

PMID- 15995503
TI  - Creation of a quality of life instrument for nonmelanoma skin cancer patients.
AB  - OBJECTIVE: Malignancies of the skin are the most common cancers among humans. The
      cervicofacial region is most affected by cutaneous malignancies, with
      approximately 80% of nonmelanoma skin cancers (NMSC) occurring in the head and
      neck. Treatment of cervicofacial skin cancers also is more likely to result in
      significant patient morbidity, because of the functional and cosmetic importance
      of this region. Unlike other malignancies, skin cancer has not been well
      investigated in terms of patient quality of life (QOL) assessment. Furthermore,
      no validated disease-specific QOL instrument currently exists for skin cancer.
      The aim of this study was to construct a new QOL instrument, The Facial Skin
      Cancer Index (FSCI), that captures the relevant QOL issues for NMSC patients.
      STUDY DESIGN: Cross-sectional study of patients presenting to a dermatologic
      surgery clinic with NMSC of the head and neck. METHODS: For stage I, item
      generation, a sample of 20 patients with cervicofacial NMSC and six health care
      providers specializing in the care of NMSC patients completed semistructured
      interviews. For stage II, item reduction, a second sample (n = 52) of NMSC
      patients rated the items in terms of their importance for QOL among skin cancer
      patients. Domains of the FSCI were evaluated in terms of data quality, item
      variability, internal consistency, and range and skewness of scale score on
      aggregation and floor and ceiling effects. RESULTS: A total of 71 distinct items
      were generated in stage I. After using the outlined item reduction techniques in
      stage II, the FSCI was reduced from 71 to 36 items, representing 6 domains. With
      the exception of Physical Functioning (alpha = 0.63) that suggested adequate
      reliability, all subscale scores showed excellent reliability coefficients, with
      Cronbach's alpha ranging from 0.78 (Lifestyle) to 0.87 (Social/Family).
      CONCLUSIONS: A new disease-specific QOL instrument for patients with NMSC of the
      head and neck has been created. Validation studies are currently underway. Future
      directions will include sensitivity analysis to determine whether the FSCI is
      sensitive to change over time among patients undergoing treatment for NMSC.

PMID- 15995504
TI  - Use, accuracy, and implications for patient management of [18F]-2
      fluorodeoxyglucose-positron emission/computerized tomography for head and neck
      tumors.
AB  - OBJECTIVES/HYPOTHESIS: Positron emission tomography (PET) has shown promise for
      early detection and accurate staging of cancer patients. A limited number of
      studies suggest PET/computed tomography (CT) may improve these variables;
      however, no published study has specifically evaluated clinical outcomes with
      PET/CT for head and neck (HN) tumors. The current study evaluates the use,
      accuracy, and implications for patient management of PET/CT scans in patients
      with HN tumors. STUDY DESIGN: Retrospective cohort outcomes study at a tertiary
      care center. METHODS: The authors identified 795 consecutive PET/CT at our
      institution. A total of 113 were obtained for HN tumors; 97 were used in the
      final analysis. Accuracy, use, and implications for patient care management
      decisions were correlated with each PET/CT scan. Multiple regression analysis was
      performed. RESULTS: Accuracy, sensitivity, and specificity were measured by
      comparing the PET/CT results at the primary tumor site, cervical node sites, and
      distant sites with either pathologic or definitive clinical diagnoses. PET/CT had
      an overall per scan accuracy of 72% and a per patient accuracy of 69%. When
      stratification for rationale of obtaining the scan was performed, accuracy was
      80% for staging distant disease, 67% for primary tumor evaluation, 72% for
      evaluation for recurrence, and 60% for unknown primary tumor evaluation.
      CONCLUSIONS: PET/CT imaging is a promising tool for evaluating HN tumors;
      however, in clinical practice, the proper use of such technology is not well
      studied. In our study, PET/CT had an overall accuracy of 72% in evaluating HN
      tumors, and PET/CT had the most accuracy in the detection of distant metastasis.

PMID- 15995505
TI  - Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the
      larynx: a clinically aggressive tumor.
AB  - OBJECTIVES: To evaluate the presentation, treatment, and outcome of a small
      series of patients with moderately differentiated neuroendocrine carcinoma (MDNC)
      of the larynx seen at one institution and to provide information on this uncommon
      laryngeal malignancy for therapeutic decision making. STUDY DESIGN: Retrospective
      analysis of medical records. Cases were identified from databases maintained by
      the medical informatics and pathology departments. METHODS: Patient, tumor,
      treatment, and outcome data were collected from medical records. Main outcome
      measures were recurrence, overall and disease-specific survival, and cause of
      death. RESULTS: Eleven patients (6 males; 5 females) seen between 1990 and 2003
      had sufficient documentation for further evaluation. Patients presented with
      dysphagia, throat pain, or hoarseness, and all tumors arose in the supraglottis.
      Eight of 11 patients gave a history of cigarette use. Of the 10 patients treated
      with curative intent, 7 who recurred all died with disease. The average disease
      free interval was 54 months, with a range of 2 to 101 months. The overall and
      disease-specific survival was 64 and 54 months, respectively. Nine patients were
      alive 3 years after diagnosis. No correlations with age, stage at presentation,
      or initial treatment modality and outcome (recurrence or survival) were found.
      CONCLUSIONS: Laryngeal MDNC is an aggressive malignancy with frequent regional
      and distant metastases. Although surgical resection is usually recommended,
      patients did respond to radiation and chemotherapy, suggesting a combined
      approach may be indicated. Aggressive initial therapy is needed because
      development of recurrence portends a poor outcome.

PMID- 15995506
TI  - Neck dissection followed by radiotherapy or chemoradiotherapy for small primary
      oropharynx carcinoma with cervical metastasis.
AB  - OBJECTIVES: A cohort of patients with small primary (T1-T2) squamous cell
      carcinoma of the oropharynx and advanced cervical nodal metastasis were treated
      with initial neck dissection(s) followed by definitive radiation therapy with or
      without chemotherapy. Our rationale for this algorithm and our results are
      examined. STUDY DESIGN: Retrospective chart review. METHODS: Pathology records
      and medical records from 1996 to 2003 from the Johns Hopkins Hospital were
      examined for patients meeting the inclusion criteria. RESULTS: Sixteen patients
      meeting the inclusion criteria were identified. Follow-up periods ranged from 6
      to 75 months. Mean and median follow-up periods were 38 and 33 months,
      respectively. One (6.25%) patient developed a metastasis and was alive with
      disease at last follow-up. Fifteen (93.75%) patients were alive without evidence
      of disease at last follow-up. Overall survival was 100%. Disease free survival
      was 93.75%. CONCLUSION: Initial neck dissection followed by primary radiation
      therapy to the primary site and neck with or without chemotherapy is an effective
      therapy for small primary oropharynx cancers with N2 or greater cervical
      metastases.

PMID- 15995507
TI  - Endoscopic versus traditional approaches for excision of juvenile nasopharyngeal
      angiofibroma.
AB  - OBJECTIVES: Juvenile nasopharyngeal angiofibroma (JNA) is an uncommon neoplasm
      originating in the nasopharynx. The purpose of this study was to determine
      whether endoscopic approaches had been effective without increasing
      intraoperative blood loss, length of hospital stay, complications, and rate of
      recurrence as compared with traditional surgical approaches. STUDY DESIGN:
      Retrospective chart review to compare outcomes in six consecutive patients who
      underwent endoscopic resection with outcomes of traditional external excision of
      JNA at Mayo Clinic between 1975 and 2004. METHODS: The medical records of
      patients who underwent either endoscopic or external surgical resection of JNA
      were reviewed retrospectively. The main outcome measures were intraoperative
      blood loss, length of hospital stay, complications, and recurrence. We review the
      reasons why we developed our current endoscopic approach to resection and
      highlight some of the obstacles we have encountered. RESULTS: We identified 65
      patients treated for JNA during the studied interval. Their mean age was 15
      (range 6-35) years. Six consecutive patients underwent successful resection of
      JNA by way of an endoscopic approach since 2001. Compared with the conventional
      surgery group, the endoscopic group had less intraoperative blood loss (225 vs.
      1,250 mL), a lower occurrence of complications (1 patient vs. > or = 30
      patients), shorter length of hospital stay (2 vs. 5 days), and lower rate of
      recurrence (0% vs. 24%). CONCLUSION: Endoscopic removal of JNA tumor appears to
      be safe and effective. Recurrence was not appreciably affected by approach.

PMID- 15995508
TI  - Program directors' opinions about surgical competency in otolaryngology
      residents.
AB  - OBJECTIVES: The purpose of this study was to determine whether certain surgical
      procedures could be used as benchmark skills to monitor resident progress in
      developing surgical competency. STUDY DESIGN: Survey. METHODS: A two-stage survey
      was sent to otolaryngology residency program directors in the United States.
      Respondents were given a list of otolaryngology surgical procedures monitored by
      the American Board of Otolaryngology (ABO) and were asked to indicate whether
      they felt residents should be able to do each as a primary surgeon. The
      appropriate level of training for competency in each procedure and estimated
      number of procedures to competency was indicated by respondents. RESULTS:
      Respondents selected 16 common procedures they felt residents at different levels
      of training should be able to perform independently. There were discrepancies
      between estimated number of procedures needed for competence and the numbers
      reported by ABO graduates. CONCLUSIONS: Surgical skill is one aspect of clinical
      competency, and this indicates agreement among program directors with regard to a
      set of benchmark skills we can use for concentrated evaluation efforts.

PMID- 15995509
TI  - Aberrant EGFR and chromosome 7 associate with outcome in laryngeal cancer.
AB  - OBJECTIVES/HYPOTHESIS: Epidermal growth factor receptor (EGFR) over-expression
      has been reported as a prognostic indicator in laryngeal cancer; however, the
      association with disease outcome has been inconsistent among studies. Here, we
      use fluorescence in situ hybridization (FISH) in addition to immunohistochemistry
      to assess laryngeal squamous cell carcinoma (SCC) to determine whether FISH can
      better predict patient outcome. STUDY DESIGN: Retrospective study on 59 patients
      presenting with advanced disease. METHODS: EGFR and chromosome 7 genomic statuses
      were measured using FISH, and EGFR expression was assessed by
      immunohistochemistry on formalin-fixed, paraffin-embedded specimens and
      correlated with outcome in the 59 patients. RESULTS: EGFR expression was
      marginally associated with outcome, whereas both EGFR and chromosome 7 FISH
      status were significantly associated with outcome, and the combination of EGFR
      and chromosome 7 FISH status provided the strongest association of any two
      combined parameters (P = .0004). Combining EGFR expression with EGFR and
      chromosome 7 FISH status provided further improvement (P > .0001). CONCLUSIONS:
      Measurements of EGFR and chromosome 7 FISH status, and to a lesser extent EGFR
      expression, have potential value in treatment planning for patients with
      laryngeal SCC.

PMID- 15995510
TI  - Effect of intratympanic dexamethasone on noise-induced temporary threshold shift.
AB  - OBJECTIVE: To evaluate the effects of intratympanic treatment of dexamethasone
      (IT-DEX) and combination of DEX and hyaluronic acid (DEX/HA) for noise-induced
      temporary threshold shift (NITTS). MATERIALS AND METHODS: NITTS was
      experimentally performed in 60 rats. Electrophysiologic hearing thresholds of the
      rats were measured before and right after noise exposure. Then, the rats were
      placed into two groups, the first 30 rats in an IT-DEX group and the second in an
      IT-DEX/HA group. Treatments were performed in the two subgroups (30 ears in one
      subgroup) of each group. In the IT-DEX group, one ear of each rat was treated
      with 0.02 mL IT-DEX, and the other ear was treated with IT 0.02 mL physiologic
      solution of serum saline. In the IT-DEX/HA group, one ear of each rat was treated
      with combination of 0.01 mL IT-DEX and 0.01 mL HA, and the other ear was treated
      with IT 0.02 mL of physiologic solution of serum saline. One week after the
      treatments, electrophysiologic hearing thresholds of all rats were measured
      again. RESULTS: No statistically significant difference was observed in recovery
      values of electrophysiologic hearing thresholds between IT-DEX and serum saline
      (P = .641) in the IT-DEX group. Also, we found no statistically significant
      difference in the recovery values of electrophysiologic hearing thresholds
      between IT-DEX/HA and serum saline (P = .344) in the IT-DEX/HA group. CONCLUSION:
      There is no effect of either IT-DEX and DEX/HA for NITTS.

PMID- 15995511
TI  - A new instrument for intraoperative assessment of individual vocal folds.
AB  - OBJECTIVES: Intraoperative assessment of vocal fold vibration during
      phonomicrosurgery performed under general anesthesia may enhance surgical
      decision-making. We therefore developed and bench-tested a new device we refer to
      as the aerodynamic vocal fold driver (AVFD). MATERIALS AND METHODS: The AVFD
      comprises a hand-held probe that uses airflow to drive individual vocal folds
      into phonatory-like vibration. This permits stroboscopic visualization of mucosal
      waves with simultaneous control of subglottal air pressure. In initial
      experiments to validate the technique, AVFD driven phonation and conventional
      whole-larynx phonation were compared using excised canine larynges (n = 14).
      RESULTS: Single vocal fold phonation using the AVFD and whole larynx phonation
      yielded similar, positive correlations between subglottal pressure and both
      amplitude and frequency of vibration. Experiments simulating vocal fold scar
      related mucosal stiffening by subepithelial injection of fixative showed the
      expected elevation of phonation threshold pressures as measured with the AVFD.
      Likewise, unilateral tissue compression injury disrupted vocal fold vibration,
      and the AVFD was useful for quantifying improvement in the damaged vocal fold
      after repair with injection of cross-linked hyaluronic acid gel. CONCLUSIONS:
      These results show that this new instrument has the potential to provide novel
      and useful information for laryngeal experimentation and to improve phonosurgery.

PMID- 15995512
TI  - Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of
      proton-pump inhibitor therapy and pretherapy predictors of response.
AB  - PURPOSE: Laryngopharyngeal reflux (LPR) is frequently treated with empiric proton
      pump inhibitors (PPI), but the optimal dosing and duration is unknown. We
      performed an open label prospective cohort study to evaluate whether twice-daily
      (BID) PPI is more effective than once-daily (QD) PPI for the treatment of LPR.
      METHODS: Patients diagnosed with LPR based on ear, nose, and throat (ENT)
      symptoms and laryngoscopy findings were enrolled. Questionnaire assessed
      demographics, ENT symptoms, symptom severity, and exposure to other potential
      laryngeal irritants. Esophageal manometry, ambulatory 24-hour pH monitoring, and
      upper gastrointestinal endoscopy were performed before initiation of therapy.
      Patients were consecutively assigned to three groups: BID PPI (lansoprazole 30 mg
      BID), BID PPI + H2 receptor antagonist (H2RA; omeprazole 20 mg BID + ranitidine
      300 mg each night), or QD PPI (esomeprazole 40 mg QD). Greater than 50% primary
      symptom improvement from baseline defined symptom response. At 2 month follow-up,
      the same PPI dose was continued for responders, and PPIs were doubled for
      nonresponders for an additional 2 months. Repeat symptom assessment and
      laryngoscopy performed at 4 month follow-up. RESULTS: Eighty-five patients were
      enrolled (median age 49 years, interquartile range 44.0 - 65.0; 76% white; 34%
      male). Treatment groups were BID PPI for 30 patients, BID PPI + H2RA for 30
      patients, and QD PPI for 25 patients. RESPONSE TO THERAPY: At 2 months, BID
      response occurred among 15 of 30 (50%) patients, BID + H2RA for 15 of 30 (50%),
      and QD for 7 of 25 (28%) (P = .03). No statistical difference found between the
      two BID PPI groups with and without H2RA. Among the QD group nonresponders, 7 of
      13 (54%) achieved symptom response with additional 2 months of BID dosing. At 4
      month follow-up, an additional 22% of responses were obtained from the two BID
      groups (43/60, 72%). The overall response rate for all three groups was 70%
      (54/77). PREDICTORS OF OUTCOME: Pretherapy interarytenoid mucosa and true vocal
      folds abnormalities were associated with twofold increase in symptom response
      (odds ratio 1.99 and 1.96, respectively, P = .017). CONCLUSION: BID PPI appears
      to be more effective than QD PPI in achieving clinical symptom response in
      suspected LPR. More response was achieved at 4 months compared with 2 months.
      Therefore, aggressive acid suppression with BID PPI for at least 4 months is
      warranted for treatment of LPR.

PMID- 15995514
TI  - Steady-state response audiometry in a group of patients with steeply sloping
      sensorineural hearing loss.
AB  - OBJECTIVES: The purpose of this study was to examine the predictive value of
      auditory steady-state response (ASSR) evoked potential thresholds and predicted
      behavioral thresholds in a group of children with steeply sloping sensorineural
      hearing loss (HL). STUDY DESIGN: Case series. METHODS: Twenty-nine children with
      sloping sensorineural HL underwent behavioral audiometric evaluation, impedance
      testing, distortion product otoacoustic emissions, and steady-state response
      testing. A t test was performed to compare the means of ASSR predicted behavioral
      thresholds and behavioral responses. Pearson correlation coefficients were
      calculated at each tested frequency, 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz,
      using the same data. RESULTS: Bracketed thresholds were obtained at 500 Hz, 1,000
      Hz, 2,000 Hz, and 4,000 Hz. Nineteen ears were used in this evaluation. A
      comparison of threshold difference as a function of bracketing revealed that the
      means were statistically different (P < .05). The mean threshold differences were
      calculated, and Pearson r values were determined between the behavioral
      thresholds and the predicted thresholds using the Rance 95 algorithm. The results
      revealed no difference of means at 500 Hz between predicted and measured
      behavioral thresholds. Linear regression analysis revealed strong correlation at
      500 Hz, 1,000 Hz, and 2,000 Hz. CONCLUSIONS: The GSI Audera appears to predict
      the configuration of HL in children with steeply sloping sensorineural HLs and
      over-predicts the severity of the loss by 15 to 20 dB above 500 Hz at each test
      frequency (1,000, 2,000, and 4,000 Hz). Correlation coefficients display a strong
      correlation at 500 Hz, 1,000 Hz, and 2,000 Hz.

PMID- 15995513
TI  - Alpha B-crystallin, a new independent marker for poor prognosis in head and neck
      cancer.
AB  - OBJECTIVES: Gene expression profiling has provided many insights into tumor
      progression but translation to clinical practice has been limited. We have
      previously identified a list of potential markers by the differences of
      expression profiling of seven matched head and neck cancer (HNSCC) tumors with
      autologous normal oral mucosa (NOM). Alpha B-crystallin (CRYAB) was in the top 5%
      of genes identified with statistically significant differences in expression
      between tumor and NOM at the mRNA level. The objective was to confirm this in
      routine paraffin sections at the protein level. STUDY DESIGN: The level of alpha
      B-crystallin was determined in tumors of 62 HNSCC patients whose prognosis was
      known for 5 years. METHODS: Immunohistochemical detection of alpha B-crystallin
      expression was performed on HNSCC paraffin sections. RESULTS: Univariate survival
      analysis identified lack of alpha B-crystallin staining as an independent
      prognostic marker for disease-free interval (P < 0.001) and overall survival (P <
      0.002) of HNSCC patients over the 5-year observation period. Notably, all 13
      patients (100%), including 5 patients with nodal disease whose tumors lacked
      alpha B-crystallin had no recurrences (P < 0.001). Nineteen of 27 node-negative
      patients stained positive for alpha B-crystallin and seven of the 19 (36.8%) had
      recurrences. CONCLUSION: Presence or absence of expression of alpha B-crystallin
      was a powerful marker for prognosis in this series of patients.

PMID- 15995515
TI  - Predictors of thyroid gland invasion in glottic squamous cell carcinoma.
AB  - OBJECTIVE: This study examines preoperative clinical and intraoperative
      histopathologic characteristics that can be used to predict thyroid gland
      invasion in the setting of squamous cell carcinoma (SCC) of the glottis. STUDY
      DESIGN: The study was retrospectively performed using 30 serially sectioned whole
      organ total laryngectomy with thyroidectomy specimens with associated
      preoperative clinical data. METHODS: Histopathologic and clinical variables
      including true vocal cord (TVC) fixation, cricoarytenoid joint invasion,
      subglottic extension (SGE) of tumor, patterns of laryngeal spread, and prior
      radiation were examined as univariate and multivariate correlates of thyroid
      gland invasion. RESULTS: Twenty-three percent of thyroid gland specimens
      demonstrated SCC invasion. Five were T4 stage, two were T3 stage, and all
      demonstrated direct extension to the thyroid gland. Of these, all had a fixed
      ipsilateral TVC (P = .003) and SGE of tumor greater than 15 mm (P = .003). Using
      multivariate analysis, SGE of tumor and TVC fixation contribute independently as
      correlates of thyroid gland invasion. Prior radiation of the larynx did not
      correlate with thyroid gland invasion and did not significantly influence the
      predictive capacity of these variables. Tumors invading the thyroid gland also
      invaded the cricothyroid membrane (100%), anterior commissure (100%), laryngeal
      ventricle (100%), and thyroid cartilage (86%). CONCLUSION: Preoperative
      assessment of TVC mobility and extent of SGE are significant correlates of
      thyroid gland invasion by SCC of the glottis. Distinct patterns of laryngeal
      spread are associated with thyroid gland invasion. Prophylactic hemithyroidectomy
      with isthmusectomy is indicated for glottic SCC in the preoperative setting of a
      fixed TVC and SGE greater than 15 mm. Additional study correlating patterns of
      laryngeal spread with thyroid gland invasion will add to these data in
      determining when to selectively perform thyroidectomy in this setting.

PMID- 15995516
TI  - Rethinking auricular trauma.
AB  - OBJECTIVES/HYPOTHESIS: An unrecognized auricular hematoma can lead to a
      disfiguring deformity, the cauliflower ear, but it can be prevented with prompt
      and comprehensive management. Fine needle aspiration with pressure bandages
      remains the mainstay treatment but will occasionally fail. We review our
      experience with recurrent or recalcitrant auricular hematomas in terms of their
      pathophysiology and revision surgery. STUDY DESIGN: Retrospective chart review.
      METHODS: A review of patients undergoing surgical incision, drainage, and
      debridement secondary to recurrent auricular hematomas was conducted. Demographic
      data was collected, intraoperative notes were reviewed, and follow-up results
      were obtained. Our management included an open incision, aggressive debridement,
      and long term bolsters to the ear. RESULTS: Ten patients presented with a
      persistent auricular hematoma and deformity following outpatient management with
      either incision and drainage or fine needle aspiration. All were male with a mean
      age of 25 years, presenting for surgery on average 19 days following initial
      trauma. The location of the hematoma within this group was not limited to the
      potential space between the cartilage and perichondrium. The hematoma was clearly
      located within the cartilage itself and it is postulated that this is one of the
      primary reasons for initial failure. Following surgical incision and drainage
      there were no recurrences or complications. CONCLUSION: There is a select group
      of patients with refractory auricular hematomas that require more aggressive
      treatment over a fine needle aspiration. Open debridement is indicated for this
      group. The location of the hematoma, granulation tissue, and neo-cartilage is
      found to be within the cartilage itself rather than between the cartilage and
      perichondrium, thus explaining why a needle aspiration alone can be ineffective.

PMID- 15995517
TI  - Management of brain herniation and cerebrospinal fluid leak in revision chronic
      ear surgery.
AB  - OBJECTIVES/HYPOTHESIS: Brain herniation and cerebrospinal fluid (CSF) leakage
      into the middle ear and mastoid are rare but described complications of chronic
      ear disease. This paper will discuss the presentation and management of brain
      herniation and/or CSF leak encountered in revision chronic ear surgery. STUDY
      DESIGN: Retrospective chart review. METHODS: Twelve of 1,130 cases of revision
      chronic ear surgery in which brain herniation or CSF leak was diagnosed were
      identified and analyzed. RESULTS: Ten (83%) patients' initial diagnosis was
      tympanic membrane (TM) perforation with cholesteatoma and two (17%) with TM
      perforation without cholesteatoma. Initial revision procedures included one
      (8.3%) tympanoplasty with canal-wall-up mastoidectomy maintaining ossicular
      continuity, two (17%) tympanoplasties with canal-wall-down (CWD) mastoidectomies
      with ossicular chain reconstruction (OCR), and nine (75%) tympanoplasties with
      CWD mastoidectomies without OCR. Three (25%) required a second procedure, two
      (17%) a third, and one (8.3%) a fourth, finally resulting in four (33%) with an
      ossicular reconstruction and eight (67%) without. Brain herniation and/or CSF
      leak were repaired by way of transmastoid and middle fossa approaches.
      Preoperative and postoperative pure-tone average air-bone gaps were statistically
      similar (33.1 and 28.1 dbHL, respectively; P = .464). CONCLUSIONS: Brain
      herniation and/or CSF leak appear to be rare complications of surgery for
      revision chronic ear disease. Their management require adherence to the
      principles of establishing a safe ear with hearing restoration as a secondary
      goal.

PMID- 15995518
TI  - Detection of Helicobacter pylori in children with otitis media with effusion: a
      preliminary report.
AB  - OBJECTIVE: To determine the presence of Helicobacter pylori in the middle ear
      effusion of patients with otitis media with effusion (OME) by polymerase chain
      reaction (PCR). STUDY DESIGN: A prospective study in patients with OME. METHODS:
      The study was performed in 38 patients with OME who were admitted to the ENT
      Clinic, Firat University from June 2003 to April 2004. In all cases, a
      myringotomy operation (with or without placement of a ventilation tube) was
      carried out. The effusion samples aspirated from the middle ear were analyzed
      with PCR assay. RESULTS: A total of 55 aspiration samples collected from 38
      children ranging in age from 2 to 12 were included in the study. Fifteen of the
      subjects were girls, and 23 were boys. In 17 patients, both ears demonstrated
      effusions, whereas in 21 patients, only one ear had effusions. Nine (16.3%) of 55
      the middle ear effusion samples were shown to be H. pylori positive by PCR.
      CONCLUSIONS: H. pylori was detected in the middle ear effusion of some patients
      with OME. These results may have interesting implications for a possible role of
      H. pylori in OME. In addition, these results suggest that further studies are
      needed to investigate the role of H. pylori in the etiology of OME.

PMID- 15995519
TI  - Functional outcomes after circumferential pharyngoesophageal reconstruction.
AB  - OBJECTIVE: To determine functional speech and swallowing outcomes, morbidity, and
      complication rates after reconstruction of circumferential pharyngoesophageal
      defects using a jejunal versus an anterolateral thigh (ALT) flap. STUDY DESIGN:
      Retrospective analysis. METHODS: We reviewed the medical records of 58 patients
      with circumferential pharyngoesophageal defects, 27 with ALT flap reconstruction,
      and 31 with jejunal interposition. We compared complication rates, intensive care
      unit (ICU) and hospital stays, nutritional intake, number of tracheoesophageal
      punctures (TEPs) performed, TE speech fluency, and functional use. Modified
      barium swallow studies assessed swallowing physiology. RESULTS: Patient
      characteristics were similar. Total flap loss occurred in one (3.7%) patient with
      an ALT flap and two (6.5%) patients with jejunal interposition (P = 1.000),
      fistula in two (7.4%) ALT patients and one (3.2%) jejunal patient (P = .5931),
      and anastomotic stricture in four (15%) ALT patients and six (19.4%) jejunal
      patients (P = .7371). ICU and hospital stays were greater for jejunal patients (P
      = .001, <.001, respectively). TEPs were performed in eight jejunal patients and
      nine ALT patients. Eighty-nine percent of ALT patients and 63% of jejunal
      patients were fluent, whereas 78% of ALT patients and 25% of jejunal patients
      used TE speech to communicate. Ninety-one percent of ALT patients and 73% of
      jejunal patients resumed oral intake (P = .151). The most common causes of
      dysphagia were impaired tongue base retraction (62% jejunum) and disordered
      motility (62% jejunum, 67% ALT). CONCLUSIONS: For circumferential
      pharyngoesophageal reconstruction, the ALT flap results in similar complication
      rates, but shorter ICU and hospital stays, and better speech and swallowing
      compared with jejunal reconstruction.

PMID- 15995520
TI  - Th1 and Th2 cell population in chronic ethmoidal rhinosinusitis: a chemokine
      receptor assay.
AB  - BACKGROUND: It is necessary for the immune system in the nasal and paranasal
      sinus mucosa to possess appropriate responses to infective agents as well as
      allergic responses. Recently, the T helper (Th)1/Th2 paradigm has been proposed
      as a new concept to explain various immunologic phenomena. OBJECTIVE: Toward the
      goal of better understanding chronic rhinosinusitis, we have tried to define the
      predominating helper T-cell subsets among patients with chronic rhinosinusitis
      through characterizing the expressed chemokine receptors by these cells to find
      out the relation between these chemokine receptors' expression and the underlying
      pathogenesis of chronic rhinosinusitis. METHODS: Thirty patients with ethmoidal
      chronic rhinosinusitis were used in our study. Patients were divided into atopic
      and nonatopic groups according to their serum immunoglobulin (Ig)E levels.
      Samples from ethmoidal sinus mucosa were processed as follows: frozen sections
      were examined immunohistochemically for detection of CCR4, CCR5, and EG2 positive
      cells and the mRNA of CCR4, and CCR5 transcripts were then examined by real-time
      quantitative polymerase chain reaction (PCR). RESULTS: By immunohistochemistry,
      atopic patients showed high expression of CCR4 and EG2 positive cells, whereas
      nonatopic patients showed high expression of CCR5 positive cells. The expression
      of CCR4 and CCR5 mRNA, detected by real-time quantitative PCR, supported the data
      obtained by immunohistochemistry. CONCLUSION: The present study suggests that
      eosinophil recruitment associated with Th2 cell infiltration is the main factor
      responsible for the pathology of atopic rhinosinusitis.

PMID- 15995521
TI  - Adenoid cystic carcinoma of the major salivary glands treated with surgery and
      radiation.
AB  - OBJECTIVE: To examine patient characteristics, pathologic features, and treatment
      outcomes of adenoid cystic carcinoma of the major salivary glands. STUDY DESIGN:
      Retrospective review of patients in an academic medical center. METHOD: Review of
      medical records regarding demographics, extent of tumor, stage, histologic
      characteristics, and treatment outcomes of patients treated with surgery and
      postoperative radiation. RESULTS: Of the 33 patients, 19 (58%) were male, and 14
      (42%) were female. The average age of presentation was 49 (range 22-81) years. Of
      the 29 patients fully staged at the time of diagnosis, 7 (24%) presented at
      American Joint Committee on Cancer stage I, 9 (31%) at stage II, 4 (14%) at stage
      III, and 9 (31%) at stage IV. The cribriform histologic subtype was predominant
      (64%). The majority originated in the parotid gland (21, 64%), with the remaining
      originating in either the submandibular gland (10, 30%) or the sublingual gland
      (2, 6%). Local control was 94% at 5 years and 73% at 10 years. Metastatic control
      was 82% at 5 years and 63% at 10 years. Four patients failed locally and nine
      failed distally. Overall survival was 85% at 5 years and 69% at 10 years, with a
      median of 12.9 years. CONCLUSION: Surgical excision with postoperative radiation
      provides a long period of disease-free survival. Patients were more likely to
      fail with metastases than with local recurrence.

PMID- 15995522
TI  - Impact of socioeconomic status on the diagnosis to treatment interval in
      Waldeyer's ring carcinoma.
AB  - OBJECTIVE: To examine the impact of socioeconomic status on the diagnosis to
      treatment interval in Waldeyer's ring cancers by comparing the experience of a
      public hospital and an academic tertiary care medical center. DESIGN:
      Retrospective review. SETTING: Otolaryngology clinic of a public hospital and an
      academic medical center. PATIENTS: One hundred seven patients with Waldeyer's
      ring carcinoma who were diagnosed and treated at San Francisco General Hospital
      (SFGH) or at the University of California, San Francisco Medical Center (UCSFMC)
      from January 1995 through December 2000 were included in the study. The same
      departments of otolaryngology-head and neck surgery and radiation oncology staff
      both hospitals. All radiation therapy was provided at UCSFMC. Patients included
      in the study had a histologic diagnosis of Waldeyer's ring carcinoma, primary
      treatment with radiation, and no prior treatment of Waldeyer's ring carcinoma.
      MAIN OUTCOME MEASURES: The time of diagnosis to start of radiation therapy, dose
      of radiation, number of treatment days, duration of treatment, and 1 and 3 year
      survival were recorded. Differences between the two groups were analyzed using
      Student's t test. RESULTS: The time course from diagnosis of nasopharyngeal
      carcinoma to start of radiation therapy was 56 days at SFGH compared with 34 days
      at UCSFMC. This difference was statistically significant (P = .0001). Difference
      in diagnosis to treatment intervals for base of tongue cancer was also
      significant at 66 days at SFGH compared with 31 days at UCSFMC (P = .0038). For
      cancer of the tonsil, the diagnosis to treatment interval was 70 days at SFGH
      versus 40 days at UCSFMC (P = .0005). Dose of radiation, number of days of
      treatment, and duration of treatment were not statistically different. Only
      patients with cancer of the tonsil demonstrated a statistically significant
      difference in 3 year survival (P = .0175). CONCLUSION: Although radiation therapy
      delivery appears similar between the public and tertiary care medical centers,
      there appears to be a statistically significant delay in the initiation of
      therapy for patients at the public institution. It is possible that this
      influences 3 year survival in cancer of the tonsil.

PMID- 15995523
TI  - Successful treatment of a postpolio tinnitus with type a botulinum toxin.
AB  - OBJECTIVES/HYPOTHESIS: Objective tinnitus is a symptom often observed in patients
      with chronic hyperactivity of masticatory muscles. METHODS: We report here the
      unusual case of a 63-year-old woman who developed a distressing tinnitus related
      to contractions of reinnervated masticatory muscles. This reinnervation process
      was caused by a postpolio syndrome that gave rise to an acoustic resonance
      phenomenon transmitted to the middle ear as an audible sound. RESULTS: The
      tinnitus was successfully treated with electromyography-guided intramuscular
      injections of type A botulinum toxin. CONCLUSION: The intramuscular injection of
      botulinum toxin was found to be effective in relieving severe and disabling
      postpolio tinnitus.

PMID- 15995524
TI  - Codetection of measles virus and tumor necrosis factor-alpha mRNA in otosclerotic
      stapes footplates.
AB  - HYPOTHESIS: Otosclerosis is a disease of unknown etiology causing conductive or
      sensorineural hearing loss. Persistent measles virus infection of the otic
      capsule is considered to be one of the etiologic factors in otosclerosis.
      BACKGROUND: Determinants of measles virus infection and reactive inflammation
      were studied in otosclerosis. The presence of measles virus was shown in
      otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR)
      amplification of the viral RNA. No report is available, however, on the types and
      features of paracrine cytokines in otosclerosis. METHODS: Nucleic acid was
      extracted from stapes footplate samples of clinically otosclerotic patients.
      Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. Tumor
      necrosis factor (TNF)-alpha mRNA expression was detected by RT-PCR in
      otosclerotic bone and was correlated with preoperative audiologic findings and
      measles virus positivity. RESULTS: Among 154 clinically otosclerotic patients, 99
      stapes footplate specimens contained measles virus RNA. TNF-alpha mRNA was
      detectable in 88 virus-positive and in 6 virus-negative stapes footplates. There
      was no detectable TNF-alpha mRNA expression in virus negative cases. CONCLUSION:
      The etiologic role of measles virus in the pathogenesis of otosclerosis should be
      considered. Detection of TNF-alpha mRNA demonstrates activated osteoclast
      functions and inflammatory pathways in otosclerotic stapes footplates associated
      with measles virus presence. Virus-associated and virus-negative pathomechanisms
      of otosclerosis should be distinguished.

PMID- 15995525
TI  - Incidence of complications in radiofrequency treatment of the upper airway.
AB  - OBJECTIVES: To investigate the incidence of complications after temperature
      controlled radiofrequency (TCRF) treatment of the inferior turbinates, palate,
      and tongue. To compare these complication rates with those reported in the
      literature. STUDY DESIGN: Prospective, observational study. METHODS: All patients
      treated with TCRF to the inferior turbinates, palate, and tongues during a 12
      month period were included. Data were collected for parameters of energy delivery
      and the development of complications. RESULTS: One hundred thirty-six patients
      were treated with a total of 470 TCRF lesions. The overall incidence of minor
      complications was 1.2% (6/470 lesions); there were no complications of moderate
      or major severity. CONCLUSION: The incidence of minor complications after TCRF in
      this series was low, and there were no complications of greater severity. These
      findings are in stark contrast with some previously published papers with higher
      complication rates. These significantly higher rates may be caused by a marked
      learning curve, problems in patient selection and the technique of application,
      excessive energy delivery, and perioperative management.

PMID- 15995526
TI  - Aural barotrauma in submarine escape: is mastoid pneumatization of significance?
AB  - OBJECTIVE: Submarine escape training is carried out by preselected, healthy young
      men under strictly controlled conditions regarding exposure to pressure and the
      rate of pressure change. This provides a unique opportunity to investigate the
      relations between middle ear characteristics and susceptibility to barotrauma
      while avoiding possible confounding parameters. We examined a possible
      association between mastoid pneumatization and middle ear barotrauma (MEB) in
      submarine escape trainees. STUDY DESIGN: Cross-sectional, parallel-group design.
      METHODS: Sixty-six subjects aged 19 to 28 participated in the study. The escape
      simulation included pressurization to 30 or 60 feet followed by a buoyant ascent
      to the surface. Subjects were evaluated for MEB after each ascent. A Schuller's
      mastoid radiograph was taken for the evaluation of mastoid pneumatization.
      RESULTS: Fifteen (23%) of the subjects suffered from MEB, and 6 (40%) of them had
      bilateral involvement. Repeated impedance audiometry after the completion of a
      successful ascent revealed a significant increase in middle ear compliance.
      Schuller's radiographs were obtained from 49 (74%) of the subjects. Of these
      radiographs, 16 (16%) were of ears that had suffered MEB. Mastoid pneumatization
      for all ears approached a normal Gaussian distribution, with a mean area of 9.58
      cm. The mastoid areas and the proportion of ears with mastoid pneumatization at
      the extremes of the study population did not differ between barotrauma and no
      barotrauma ears. CONCLUSION: In a population with no history of recurrent or
      chronic otitis media and normal tympanic membrane morphology and compliance, the
      amount of mastoid pneumatization probably represents merely the normal
      distribution of variation in organ size and is not related to the ability to
      equalize pressure in the middle ear.

PMID- 15995527
TI  - Continuous facial nerve monitoring during pleomorphic adenoma recurrence surgery.
AB  - OBJECTIVES: Surgery of recurrent pleomorphic adenoma (RPA) is known to lead to a
      high facial nerve complication rate. The efficacy of the continuous facial nerve
      monitoring (CFNM) technique remains to be proven in RPA surgery. The goal was
      thus to evaluate facial nerve palsy rates and the recovery period after
      parotidectomy for RPA using CFNM by way of continuous electromyography and to
      compare these rates and the operation time with those of patients who had
      undergone surgery without facial nerve monitoring. DESIGN: Cohort study.
      PATIENTS: Forty-seven patients were referred for RPA (1981-2003). Among them, 32
      (18 unmonitored and 14 monitored) patients displayed no preoperative facial
      palsy, and histologic analyses revealed evidence of recurrence. The operation
      time and the extent and duration of postoperative facial nerve palsy were
      examined in both groups (monitored vs. unmonitored). Both groups had a similar
      clinical appearance distribution. RESULTS: Facial nerve paralysis was estimated
      using the House-Brackmann grading scale. CFNM reduced the intensity of facial
      nerve paralysis independently of the kind of surgery performed. The complete
      deficit rates were 0% for the monitored group and 5.6% for the unmonitored group.
      Postoperative facial nerve paralysis was significantly lower (P = .01) in the
      monitored group than in the unmonitored group. CFNM improved the duration of
      facial paralysis (P = .001) in the monitored group. The operation time was
      significantly lower in the monitored group than in the unmonitored group (P =
      .001). CONCLUSIONS: Routine use of CFNM during RPA surgery improves the surgical
      outcome. The facial nerve deficit can be reduced, and the recovery of facial
      nerve function is faster.

PMID- 15995528
TI  - Transoral robotic surgery: supraglottic laryngectomy in a canine model.
AB  - OBJECTIVES/HYPOTHESIS: To develop a technique for computer enhanced robotic
      transoral supraglottic partial laryngectomy in the canine model. STUDY DESIGN:
      Surgical procedure on the larynx in a canine model with a commercially available
      surgical robot. METHODS: With use of the da Vinci Surgical Robot (Intuitive
      Surgical, Inc., Sunnyvale, CA), the supraglottic partial laryngectomy was
      performed on a mongrel dog that had been orotracheally intubated using general
      anesthesia. The videoscope and the 8 mm end-effectors of the robotic system were
      introduced through three ports, transorally. The surgical procedure was performed
      remotely from the robotic system console. The procedure was documented with still
      and video photography. RESULTS: Supraglottic partial laryngectomy was
      successfully performed using the da Vinci Surgical Robot, with 8 mm
      instrumentation. The robotic system allowed for celerity and accuracy secondary
      to findings specific to the surgical approach, including excellent hemostasis,
      superb visualization of the operative field with expeditious identification of
      laryngeal submucosal soft tissue and skeletal landmarks, and multiplanar
      transection of tissues. In addition, the use of the robotic system also was found
      to have technical advantages inherent in robotic surgery, including the use of
      "wristed" instrumentation, tremor abolition, motion scaling, and three
      dimensional vision. CONCLUSIONS: The da Vinci Surgical Robot allowed for
      successful robotic transoral supraglottic partial laryngectomy in the canine
      model.

PMID- 15995529
TI  - Significance of nasal polyps in chronic rhinosinusitis: symptoms and surgical
      outcomes.

PMID- 15995530
TI  - Is oxymetazoline really safe for middle ear use.

PMID- 15995531
TI  - Familial nonmedullary thyroid cancer.

PMID- 15995533
TI  - Which one is the etiologic factor: gastroesophageal reflux disease or larynx
      cancer?

PMID- 15995537
TI  - Changes in Obstetrics and Gynecology 1946-2005.

PMID- 15995541
TI  - A testimony: the wisdom of Drs. Eastman and Novak.

PMID- 15995562
TI  - Mullerian agenesis and thrombocytopenia absent radius syndrome: a case report and
      review of syndromes associated with Mullerian agenesis.
AB  - Mullerian agenesis, commonly referred to as Mayer-Rokitansky-Kuster-Hauser
      syndrome (MRKHS), is a congenital defect that is most commonly associated with
      renal and spinal malformations. It is very rare for Mullerian agenesis to be
      accompanied by malformations of the extremities. In this report, we describe a 22
      year-old woman with Mullerian agenesis and thrombocytopenia absent radius
      syndrome (TARS). We also review rare syndromes associated with Mullerian
      anomalies, including Mullerian hypoplasia/aplasia-renal agenesis-cervicothoracic
      somite dysplasia (MURCS), Roberts syndrome, Bardet-Biedl syndrome (BBS), McKusick
      Kaufman syndrome (MKS), Wolf-Hirschhorn syndrome, and others. The pathogenesis of
      these complex malformation syndromes is not well understood as a result of their
      sporadic occurrence. However, some of these syndromes do follow a pattern of
      inheritance, suggesting that they could provide insights into our understanding
      of their origins. TARGET AUDIENCE: Obstetricians & Gynecologists, Family
      Physicians LEARNING OBJECTIVES: After completion of this article, the reader
      should be able to review the rare congenital defects associated with Mullerian
      agenesis, to determine the genetic etiologies of the associated syndromes with
      Mullerian agenesis, and to discuss information for parental counseling related to
      inheritance patterns and growth and development of the affected child.

PMID- 15995563
TI  - Management of wound complications from cesarean delivery.
AB  - Multiple factors account for the increasing number of cesarean delivery wound
      complications in the United States; among them are an increase in cesarean
      delivery and an increase in the number of overweight and obese patients. This
      article reviews the pathophysiology of acute wound healing. Risk factors for
      cesarean delivery wound complications are identified and described. Clinical
      practices that can reduce the risk of developing wound complications, including
      Centers for Disease Control and Prevention guidelines, are considered. Treatment
      guidelines to accelerate wound healing such as secondary closure and negative
      pressure wound therapy in disrupted wounds are proposed. Older guidelines for
      management of wounds using secondary intention are critiqued. Historical methods
      of wound care such as the practice of using certain cleansers and the practice of
      wet to dry dressings are outdated. Modern wound healing products are described.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING
      OBJECTIVES: After completion of this article, the reader should be able to
      describe the effects of obesity on cesarean delivery wound healing, to improve
      methods of wound healing in the obese patient, and to explain why wet to dry
      dressing changes are not effective wound management.

PMID- 15995564
TI  - Musculoskeletal causes of chronic pelvic pain: a systematic review of existing
      therapies: part II.
AB  - Chronic pelvic pain is a common clinical problem with many causes. In addition to
      gynecologic causes, it is important to evaluate other potential etiologies,
      including the pelvic musculoskeletal system. There have been few published
      studies on musculoskeletal causes of pelvic pain and its treatment. The objective
      of this study was to evaluate treatment of pelvic musculoskeletal pain among
      women with chronic pelvic pain. We used a set of key words pertaining to pain and
      the pelvic musculoskeletal structures to initially review the PUBMED database.
      Additional articles were sought by discussion with a clinician specializing in
      this field and review of relevant textbook bibliographies. Study inclusion was
      restricted to English-language publications that reported a patient-related
      chronic pelvic pain outcome measure. Each report must have described at least
      four patients. For each selected article, two investigators separately summarized
      pertinent data on study characteristics, patient profiles, intervention
      characteristics, and treatment outcomes. Discrepancies were resolved by
      discussion. Twenty-nine treatment studies met entry criteria. The existing
      literature largely consists of retrospective, uncontrolled observational studies.
      The two studies that feature control groups lack sufficient size and scope to
      allow generalizability. Properly designed and executed randomized, controlled
      trials are urgently needed to determine the true effectiveness of treatments for
      pelvic musculoskeletal pain. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians LEARNING OBJECTIVES: After completion of this article, the
      reader should be able to summarize the current data on musculoskeletal causes of
      chronic pelvic pain, to outline the various techniques used to treat
      musculoskeletal causes of chronic pelvic pain, and to recall the lack of evidence
      based data on the subject and need for randomized controlled trials.

PMID- 15995569
TI  - Dental death rate prevalence in smokers and non smokers adults with periodontal
      disease.
AB  - The current study target was to evaluate the dental loss pattern in an adult
      population with periodontal disease who was treated at the Periodontal Chair,
      Dentistry Faculty, National University of Rosario, Argentina. The sample was of
      203 patients, 130 women and 73 men; 75 of them were blond cigarette smokers and
      128 of them were not in that habit. Inclusion criteria as follows: good systemic
      condition given by the absence of illnesses that may be risky for the development
      of a periodontal disease, and the presence of at least one teeth with insertion
      loss of 2 mm. minimum in its proximal faces. The age average of the group was
      37,83 years (IC 95% 34,46-41,19) for smokers, and 40,98 (IC 95% 38,27- 43,69)
      years for non smokers. Regarding females, 85 of them were non smokers and 45 had
      that habit; concerning men 43 were non smokers and 30 were indeed. The
      independence test made under smoking and sex variables showed no significant
      relation between them. Regarding smoker group the smoked cigarette average per
      day (daily doses) was 13,27 cigarettes (IC 95% 10,96-15,57) and the time since
      habit started in measure of months was 193,57 (IC 95% 160,43-226,81). The death
      rate for tooth loss in each group was 4,71 teeth (CI 95 % 3,43-5,98) for smokers
      and 5,05 teeth (CI 95% 4,07-6,03) for non-smokers. Setting the probability of
      error of type I equal to 0.05, this study demonstrated that in this group of
      patients with periodontal disease, the tooth loss in smoker individuals was
      similar to the tooth loss in non-smoker individuals.

PMID- 15995568
TI  - Capacity buffer of the saliva in children and adolescents with cancer: Variations
      induced by the administration of metotrexate or cyclophosphamide.
AB  - OBJECTIVE: To determine the variations in the levels of capacity buffer of the
      saliva in children and adolescents with cancer that receiving Metotrexate or
      cyclophosphamide. MATERIALS AND METHODS: A clinical, random-controlled assay was
      carried out. The sample was composed by 24 children, ages between 2 and 16 years,
      with diagnostic of Leukemia and Lymphomas attending to The Autonomous Service of
      University Hospital of Maracaibo and Hospital of Pediatric Specialties. Two
      groups were conformed to which a sample of saliva was taken before and after the
      chemotherapy; twelve patients were randomly placed in the G1: patient receiving
      Metotrexate and twelve in the G2: patient receiving cyclophosphamide. In order to
      determine the capacity buffer, the CRT Buffer IVOCLAR VIVADENT was used. RESULTS:
      The capacity salivary buffer did not show significant differences before and
      after the administration of the cytostatic agents studied. CONCLUSIONS: In this
      study, the Metotrexate or cyclophosphamide administration does not modify the
      salivary buffer capacity in pediatric patient with cancer.

PMID- 15995570
TI  - Denture hyperplasia with areas simulating oral inverted ductal papilloma.
AB  - Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated
      to an ill-fitting denture. This lesion is easily diagnosed and in some cases
      distinct microscopic variations such as osseous, oncocytic and squamous
      metaplasia may be found. These metaplastic alterations probably are associated
      with the lymphocytic infiltrate usually present in denture hyperplasia. We
      present a case of denture hyperplasia containing salivary gland tissue with
      ductal alterations mimicking an oral inverted ductal papilloma.

PMID- 15995571
TI  - Incontinentia pigmenti (IP2): familiar case report with affected men. Literature
      review.
AB  - Incontinentia pigmenti is a genodermatosis described by Garrod and in 1920 by
      Bloch, Sulzberger, Siemens y Bardach. It is an ectodermic disorder that affects
      skin, teeth, eyes and may also have neurological problems. The IP2 name describes
      the histological characteristics, the incontinence of melanin into the
      melanocytes cells in the epidermal basal layer and its presence in superficial
      dermis. IP2 is an x-linked dominant condition but genetic heterogeneity may
      exist. CASE REPORT: The patient was 4 yrs 5 months old when she came for the
      first time. In a physical exploration she presented sparse and thin hair,
      eyelashes and eyebrows, beaked nose, labial protrusion, the four central teeth
      have a conic crown and there was also a delayed eruption of other teeth, right
      eye strabismus, hipoacusia, language defects and a trunk, legs, feet, and face
      dermatosis characterized by grouped vesicles, hyperkeratotic and warty lesions
      and brownish-gray lesions in a lineal pattern. The patient s father had
      hypopigmented lesions in the posterior regions of both legs. The oral clinical
      and radiographic exams showed diverse anomalies. Both the patient's and the
      father's chromosomal studies were normal. DISCUSSION: In the present case we can
      see that the father has IP2 without supernumeraries X, with the antecedent that
      his mother had something similar. It is possible that the inheritance was
      autosomic dominant or it is a different mutation of NEMO (NF-kappa-B essential
      modulator) gene to a classical one, which was found in some affected men. It is
      necessary to carry out a molecular study of these patients.

PMID- 15995572
TI  - Central giant cell granuloma and fibrous dysplasia occurring in the same jaw.
AB  - Fibrous dysplasia (FD) is a developmental tumor like condition that is
      characterized by replacement of normal bone by an excessive proliferation of
      cellular fibrous connective tissue intermixed with irregular bony trabeculae.
      Central giant cell granuloma (CGCG) is described as a benign lesion affecting the
      mandible and maxilla that consists of a massive fibrohistiocytic proliferation
      with numerous heavily hemosiderin-laden multinucleate-giant cells. A 20 year old
      woman present at the Department of Oral Medicine, Dentistry School, Tehran
      University of Medical Sciences with a slowly growing non painful swelling of the
      right mandible for one year. Our differential diagnosis was osteoma, osteoid
      osteoma and Fd. The histological feature reveal Central giant cell granuloma
      fibrous dysplasia. Central giant cell granuloma and fibrous dysplasia occurring
      in the same jaw is rarely reported in the literatures.

PMID- 15995573
TI  - Condylar disk plication for temporomandibular joint internal derangement
      treatment: surgical technique and results.
AB  - OBJECTIVE: To report six cases submitted to the TMJ condylar disk plication
      technique. STUDY DESIGN: All patients presented a limitation of mandibular
      movements, severe pain and failure of previous clinical treatment. A definitive
      diagnosis of irreducible anterior disk displacement was made by MRI (Magnetic
      Resonance Imaging). Clinical evaluation consisted of the following: measurement
      of maximal mouth opening, movement to the left and right and protusion; presence
      of deviation during mouth opening; clicking during mouth opening or closing;
      presence of pain and personal satisfaction following surgery. RESULTS: While all
      patients had preoperative pain, only one had severe pain; in the others, the pain
      was less intense at the end of the period of follow-up. Stomatognatic function
      was improved and has been maintained since the conclusion of this study.
      CONCLUSIONS: On the basis of the follow-up of these patients, the proposed
      technique proved to be effective for disk stabilization, leading to a decrease in
      pain and an improvement in mandibular movements.

PMID- 15995574
TI  - Peripheral osteoma of the maxillofacial region. Diagnosis and management: a study
      of 14 cases.
AB  - PURPOSE: The purpose of the article was to present 14 new cases of peripheral
      osteoma and to evaluate the diagnosis and management of peripheral osteoma of the
      maxillofacial region with an analysis of the literature. PATIENTS AND METHODS:
      The records of 14 consecutive patients (6 males and 8 females) referred for the
      management of peripheral osteoma the maxillofacial region were reviewed.
      Demographic data, location, presenting symptoms, radiographic findings, bone
      scan, colonoscopy results and surgical management were analyzed. The criteria
      used to diagnose peripheral osteoma included radiographic and histologic
      features. RESULTS: The 14 patients, ranged in age from 13 to 79 years with a mean
      age of 40.5 years. The lesions were located in the mandible (64%), maxilla (7%),
      temporal bone (22%) and maxillary sinus (7%). Colonoscopy results performed in 10
      subjects were negative. Surgical excision was the treatment of choice with good
      results. There were no complications or recurrences. CONCLUSIONS: Peripheral
      osteoma of the jaw bones is uncommon. The post surgical follow-up should include
      periodic clinical and radiographic studies. Patients with osteoma associated with
      impacted or supernumerary teeth, should be evaluated for the possible Gardner's
      syndrome.

PMID- 15995575
TI  - Immediate loading in oral implants. Present situation.
AB  - The earliest antecedents of immediate loading were introduced by Ledermann in
      1979. He placed overdenture in four interforaminal implants on the same day the
      surgery was carried out. In the original implantological protocol of Branemark
      the immediate loading did not appear indicated, currently, it is being presented
      as a predictable alternative in several studies. We revised different articles on
      immediate loading from 1997 to 2002. We analysed different variables and
      concluded that immediate loading produces a success rate in posterior maxilla
      similar to the differed loading (90-100%). The characteristics of the implant,
      favourable to immediate loading, are: screw-shaped, with a rough surface, sand
      blasted and acid etching processed and a minimum length of 10 mm. The initial
      stability and a micro movement of the implant, inferior to 150 microm and a
      marginal to the insertion equal or superior to 32 N/cm are defined as a proper
      osseous. The bruxism stands out as an adverse factor according to several
      authors.

PMID- 15995576
TI  - Central odontogenic fibroma: a case report.
AB  - OBJECTIVE: The aim of this case report was to analyze clinical and histological
      features of a central odontogenic fibroma followed up for 6 years after surgical
      excision. METHODS: A 26-year old Caucasian female was referred, reporting a
      painless gingival swelling in the buccal area of the maxillary right canine.
      There were no other symptoms and no recent history of pain. Her medical history
      was non-contributory. Radiographic evaluation showed the presence of a
      radiolucent area with well-defined margins. The lesion was surgically removed and
      histologically analysed. RESULTS: Histologic analysis showed a cellular
      fibroblastic tissue characterized by interwoven bundles of collagen densely
      packed and absence of odontogenic epithelium. The surgical site was monitored for
      6 years after surgery with no signs of recurrence. CONCLUSION: The central
      odontogenic fibroma here reported displayed a prominent quantity of collagen and
      absence of odontogenic epithelium. The surgically removed lesion had a favourable
      prognosis and no recurrence for the 6 year follow-up period.

PMID- 15995577
TI  - Bisphosphonates, as a new cause of drug-induced jaw osteonecrosis: an update.

PMID- 15995578
TI  - Valuation of exfoliative cytology as prediction factor in oral mucosa lesions.
AB  - The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in
      order to evaluate their expression in premalignant and malignant stomatological
      lesions in oral epithelial, and to compare this expression with exfoliative
      cytology alterations in the same patients. It was studied biopsies and cytologies
      of 13 subjects with oral lichen planus, with or without Human Papilloma Virus
      (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed
      by anatomopathological studies. The oral lichen planus lesion presented binuclei
      orange cells; and in leukoplakia lesions only orange stained was observed;
      meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic
      microorganisms were observed in the HPV infections and squamous cells carcinoma
      (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the
      leukoplakia, oral lichen planus and cancer. Cytological alterations and positive
      immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial
      stratus should be indicator of malignant transformations as doing subsequence
      exams.

PMID- 15995579
TI  - Pneumolysin as a vaccine and drug target in the prevention and treatment of
      invasive pneumococcal disease.
AB  - Streptococcus pneumoniae (the pneumococcus) remains one of the major human
      pathogens and one of the most common causes of community-acquired pneumonia,
      otitis media, sinusitis, and meningitis. Aside from the threats posed by emerging
      antibiotic resistance and infection with the human immunodeficiency virus, the
      mortality rate among those patients with severe pneumococcal disease who receive
      seemingly appropriate antimicrobial chemotherapy remains unacceptably high.
      Because of its involvement in the pathogenesis of invasive disease, pneumolysin,
      one of the best-characterized virulence factors of the pneumococcus, represents
      not only a potential vaccine target, but also a target for adjunctive therapy to
      antibiotics in patients with acute pneumococcal disease. In this paper we review
      the cytolytic and pro-inflammatory properties of pneumolysin and their
      involvement in subversion of host defenses and extra-pulmonary dissemination of
      the pneumococcus, as well as strategies, both immunological and pharmacological,
      which may counter these harmful activities of the toxin.

PMID- 15995580
TI  - Phagocyte NADPH oxidase: a multicomponent enzyme essential for host defenses.
AB  - Phagocytes such as neutrophils and monocytes play an essential role in host
      defenses against microbial pathogens. Reactive oxygen species (ROS), such as
      superoxide anion, hydrogen peroxide, the hydroxyl radical, and hypochlorous acid,
      together with microbicidal peptides and proteases, constitute their antimicrobial
      arsenal. The enzyme responsible for superoxide anion production and,
      consequently, ROS generation, is called NADPH oxidase or respiratory burst
      oxidase. This multicomponent enzyme system is composed of cytosolic proteins
      (p47phox, p67phox, p40phox, and rac1/2) and membrane proteins (p22phox and
      gp91phox, which form cytochrome b558) which assemble at membrane sites upon cell
      activation. The importance of this enzyme in host defenses is illustrated by a
      life-threatening genetic disorder called chronic granulomatous disease in which
      the phagocyte enzyme is dysfunctional, leading to life-threatening bacterial and
      fungal infections. Also, because ROS can damage surrounding tissues, their
      production, and thus NADPH oxidase activation, must be tightly regulated. This
      review describes the structure and activation of the neutrophil NADPH enzyme
      complex.

PMID- 15995581
TI  - Systemic lupus erythematosus--recent clues from congenic strains.
AB  - Systemic lupus erythematosus is a polycongenic autoimmune disease characterized
      by the production of antinuclear antibodies that lead to subsequent end organ
      damage. The study of lupus is complicated by its polycongenic origin,
      contributions from hormones and the environment, epistasis among susceptibility
      loci, suppressive modifiers, and the fact that a single susceptibility locus may
      encompass multiple susceptibility genes. Murine models that develop lupus
      spontaneously have greatly contributed to our understanding of this disease. In
      particular, the advent of "congenic strains" has greatly simplified the study of
      this complex autoimmune disease. Thus, congenic strains bearing NZB/NZW/NZM2410,
      BXSB, and MRL lupus susceptibility loci are steadily replacing the traditionally
      studied murine lupus models as the models of choice for research. This review
      summarizes how researchers have used congenic strains over the past few years to
      dissect out and reconstruct the individual elements contributing to lupus
      pathogenesis.

PMID- 15995582
TI  - The biology and pathology of hypoxia-ischemia: an update.
AB  - After an hypoxic-ischemic (HI) insult, a multi-faceted complex cascade of events
      occurs that ultimately causes cell death and neurological damage to the central
      nervous system. The various cascades include, amongst others: immunological
      changes, such as the activation of the complement system and the generation of
      antibodies; increased inflammation through the actions of pro-inflammatory
      cytokines and chemokines; the production of reactive oxygen species leading to
      oxidative stress; and diminished mitochondrial function leading to the activation
      of apoptotic pathways and subsequent alteration in the function of neurons within
      the contralateral hemisphere. This review addresses the immunological aspects
      following HI, the role of various cytokines (both pro-inflammatory and anti
      inflammatory) and chemokines after the induction of HI. In addition, the role of
      free radicals in producing HI-induced neurodegeneration and the contribution that
      mitochondrial dysfunction has in neuronal apoptotic cell death will be discussed.
      This review also covers the changes that the previously assumed "internal
      control", the contralateral hemisphere, undergoes due to HI and describes the
      difficulties associated with therapy intended to prevent neuronal injury
      associated with HI.

PMID- 15995583
TI  - New biodefense strategies by neutrophils.
AB  - Chemokines and other chemotactic factors induce neutrophils, macrophages, and
      dendritic cells to migrate to an inflammatory site and efficiently ingest and
      destroy infective microorganisms. Moreover, antigen-presenting cells, such as
      macrophages and dendritic cells, present the microbial antigens via major
      histocompatibility complex class II molecules, resulting in the activation of
      specific CD4 T cells. Since neutrophils have a short life-span and are highly
      susceptible to apoptosis, their role in antigen presentation has been questioned.
      However, various pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6,
      tumor necrosis factor alpha, and interferon gamma, produced at the site of
      inflammation activate neutrophils and suppress apoptotic death. These cytokine
      activated neutrophils show enhanced expression of cell surface molecules and
      become as competent as dendritic cells and macrophages in their ability of
      antigen presentation. Traditionally, neutrophils are known to be responsible for
      innate immunity, and recently they are also considered to be intimately
      associated with the establishment of acquired immunity. In the present review on
      the role of neutrophils we describe both classic innate and acquired immunity.

PMID- 15995584
TI  - Cellular responses to attaching and effacing bacteria: activation and implication
      of the innate immune system.
AB  - During the last decade, research on attaching-effacing (A/E) bacteria/host cell
      interactions has revealed much of the molecular basis of colonization and lesion
      formation. The colonic mucosa represents the first line of defense against these
      pathogens, and its integrity is required to avoid translocation of bacteria or
      bacterial soluble factors into the infected host. Therefore, the cellular immune
      response to A/E pathogens plays an important role in bacterial pathogenesis since
      it can clear the bacteria or modulate the inflammatory processes. Data obtained
      from infected patients demonstrate a correlation between the production of pro
      inflammatory cytokines and the severity of the disease. In vitro studies of
      infected epithelial cells have clearly elucidated A/E bacteria-induced host
      signal transduction events. However, the identification of the bacterial factors
      responsible for cellular activation remains a subject of controversy.
      Experimental studies with knock-out mice infected with Citrobacter rodentium, a
      rodent A/E pathogen, indicate that innate immunity is an essential component of
      pathogenesis. This review summarizes in vivo and in vitro evidence for the
      induction and potential role of the innate immune system during infection with
      A/E bacteria.

PMID- 15995585
TI  - Innate immunity: cells, receptors, and signaling pathways.
AB  - Essential differences between the innate and acquired branches of immunity are
      described. These differences concern the detection system (receptors and pathogen
      structures) and the cells engaged in both systems as well as the effectory
      mechanisms. In contrast to those of the acquired system, receptors of the innate
      system, which developed during evolution, recognize unchanged structures on large
      groups of pathogens (e.g. lipopolysaccharide in Gram-negative bacteria). Two
      lineages, natural killer (NK) and dendritic cells (DCs), play important roles in
      the innate system. Phenotypic and functional differentiation is observed among
      NKs and DCs, so each of their sublineages plays a different role in the innate
      system. Every lineage of cells of the innate immune system express different
      stimulatory and sometimes also inhibitory receptors on their surfaces (e.g. NK
      cells). Among the stimulatory are Toll-like receptors (TLRs), mannose and
      scavenger receptors, and the stimulatory receptors of NK cells. All TLRs show
      similarity in structure and in the kind of molecules involved in intracellular
      signaling. The immune reactions of the innate system involve cytokine-dependent
      resistance of cells against infection with pathogen, production of cytokines
      (tumor necrosis factor, interferons, interleukins, chemokines) and MHC
      independent killing. Although these reactions protect the host from invasion by
      microorganisms, they can also be responsible for significant tissue damage or may
      stimulate the development of autoimmunity. Therefore innate immunity must be
      under rigorous control. The possible regulatory mechanisms of innate immunity are
      discussed.

PMID- 15995586
TI  - Evaluation of interleukin-1 and -6 in the etiopathogenesis of idiopathic
      osteoporosis and osteopenia in children.
AB  - INTRODUCTION: The aim of the study is to determine whether serum concentrations
      of interleukin (IL)-1and IL-6 correlate with indices of bone mineral metabolism
      in children with idiopathic osteoporosis and osteopenia. MATERIAL/METHODS: The
      study comprised 62 patients aged 6-18 years (20 with idiopathic osteoporosis, 22
      with idiopathic osteopenia, and 20 controls). In 10 children, investigations were
      repeated after one year of treatment. Serum concentrations of IL-1alpha, IL
      1beta, IL-1 receptor antagonist (IL-1ra), as well as IL-6 and its soluble
      receptor (IL-6sR) were determined by the ELISA method. In patients with decreased
      bone mass, selected calcium-phosphorus metabolism indices and bone turnover
      markers were assessed. RESULTS: Higher values of IL-6 were recorded in those with
      idiopathic osteoporosis than in controls (2.79 vs. 1.43; p<0.05). In these
      patients there was also a tendency towards higher values of IL-6sR (p=0.05). IL
      1alpha and IL-1beta were not markedly elevated in any of the patients. No
      significant differences between groups regarding IL-1ra were observed. Negative
      correlation between IL-6, IL-1alpha, cytokine/receptor indices, and spinal bone
      mineral density was determined. Positive correlation was found between IL-alpha,
      IL-1/IL-1ra, and parathormon as well as between IL-1alpha, IL-6sR, and bone
      formation markers.markers. Increase in bone mass after treatment was accompanied
      by a decrease in IL-6sR. CONCLUSIONS: The higher serum levels of IL-6 in children
      with idiopathic osteoporosis/osteopenia and the decrease in IL-6sR after
      treatment reveal an involvement of IL-6 in the etiopathogenesis of these
      disturbances. The results suggest that IL-1 may also participate in the primary
      decrease of bone mass in children.

PMID- 15995587
TI  - Expressions of selected adhesion molecules on peripheral blood leukocytes in
      patients with aggressive periodontitis.
AB  - INTRODUCTION: Aggressive forms of periodontitis lead to rapid bone destruction
      resulting in extensive losses in children's and young adults' dentition. Adhesion
      molecule deficiency syndrome and abnormalities in the expression of various
      adhesion molecules on peripheral blood leukocytes can be observed in prepubertal
      and aggressive periodontitis (AP) patients. The aim of the study was thus to
      assess the expression of selected cell adhesion molecules (CAMs; CD11a, CD11b,
      CD11c, CD54, and CD62L) on monocytes, neutrophils, and lymphocytes of the
      peripheral blood in patients with AP. MATERIAL/METHODS: The study involved 16
      patients with AP and a control group of 13 generally healthy subjects with
      healthy periodontium. CAM expressions were determined by flow cytometry and
      presented as mean fluorescence intensity (MFI) and percentage of cells showing
      expression of the assessed adhesion molecules. RESULTS: Neutrophil CAM
      expressions in AP patients were comparable with those of the control group. MFI
      of CD62L on monocytes in AP patients was significantly lower than that of the
      controls. Lymphocytes showed increased CD11b expression compared with the control
      group. The percentage of leukocytes showing CAM expression in both groups was
      similar. Only the percentage of lymphocytes with CD11b in AP patients was
      significantly higher than in healthy controls. CONCLUSIONS: Because of the
      evident lack of differences between patients and controls and the great amount of
      individual dispersion of the results, the above CAMs on peripheral blood
      leukocytes in generally healthy patients with AP do not seem to be characteristic
      markers of this disease.

PMID- 15995588
TI  - Effect of cardiopulmonary bypass on neutrophil activity in pediatric open-heart
      surgery.
AB  - INTRODUCTION: The nature of the participation of neutrophils in the post
      cardiopulmonary bypass (CPB) inflammatory response is not very clear. The aim of
      our study was to investigate alterations in neutrophil phagocytic activity and
      adhesion molecule expression on these cells in children during and after CPB.
      MATERIAL/METHODS: Twenty-one children aged 6-33 months with congenital heart
      disease, scheduled for pri mary corrective surgery, were enrolled. The
      expressions of CD11b adhesion molecules and Fc? receptor on neutrophils and their
      phagocytic activity were evaluated. The studied markers were sequentially
      measured before, at the initiation of, and after CPB. RESULTS: During the course
      of the operation, CD11b molecule expression on neutrophils showed a slight
      elevation at the start of CPB (876.5+/-104.8 mean fluorescence intensity, MFI,
      vs. 768.1+/-178.2; p = 0.0047), followed by a significant decrease to 689.01+/
      166.7 MFI after completion of the procedure. The expression of CD11b molecule on
      neutrophils measured at the end of CPB inversely correlated with the duration of
      CPB (r = -0.68, p = 0.00059). The expression of CD16 antigen dropped
      significantly at the start of CPB (1164.6+/-307.3 MFI vs. 1327.4+/-345.3 MFI; p =
      0.0007) and remained decreased until the end of CPB (814.0+/-198.1 MFI).
      CONCLUSIONS: These findings suggest that the characteristics of the neutrophil
      response to cardiac surgery appear to depend on many factors. We demonstrated a
      link between the duration of CPB and adhesion molecule expression on neutrophils.

PMID- 15995589
TI  - [The musculoskeletal system in diabetic patients].
AB  - In this review, musculoskeletal manifestations in diabetic patients are
      presented. Late complications of diabetes mellitus (neuropathic arthropathy and
      diabetic muscle infarction), consequences of metabolic derangement inherent to
      diabetes (diffuse idiopathic skeletal hyperostosis, osteopenia, and
      osteoporosis), syndromes that may share etiologic mechanisms with changes of
      collagen and microvascular disease (limited joint mobility syndrome
      (cheiroarthropathy), palmar flexor tenosynovitis (trigger finger), Dupuytren's
      disease, adhesive capsulitis of the shoulder, and reflex sympathetic dystrophy)
      are described. Moreover, carpal tunnel syndrome, gout, osteoarthritis and their
      probable association with diabetes mellitus are discussed.

PMID- 15995590
TI  - [Molecular basis of HLA class-I deficiency and bare lymphocyte syndrome (BLS)].
AB  - Molecules of human leukocyte HLA class I antigens play a crucial role in the
      presentation of endogenic peptides, allowing effector cells of the immune system
      to control the immune homeostasis of the host. There are rare immunodeficiencies
      which result in impaired HLA antigen expression on cell membranes and which are
      called bare lymphocyte syndrome (BLS). These diseases allow us to gain insight
      into the roles of antigen-processing pathways in HLA class I expression and into
      the genetic disorders of transcription factors crucial to the expression of HLA
      class II molecules. Moreover, the clinical pictures of BLS patients provide us
      with a rare opportunity to study the host's immune responses when one of the most
      important immune mechanisms is impaired. In this study we present disorders of
      endogenic antigen-presentation pathways and point out pathways which, at least in
      part, allow the host to overcome these defects. We also present hypotheses that
      may explain the clinical findings in BLS patients.

PMID- 15995591
TI  - [Mechanisms of innate immunity].
AB  - Innate (natural) immunity differs from acquired immunity with respect to the
      detection systems (receptors and structures detected on pathogens), the cells
      engaged, and the nature of the mechanisms. Innate immunity is an ancient system,
      with similar structures in plants, invertebrates, and vertebrates are involved in
      the development of defense against pathogens. Toll-like receptor (TLR) structures
      are present in all organisms, and some mechanisms (i.e. complement activation)
      were also discovered in invertebrates and vertebrates. During infection, innate
      reactions develop before acquired immune reactions do. Natural immunity involves
      such reactions as the production of different cytokines, chemokines, and
      interleukins; the innate, cytokines-dependent nonspecific immunity of leukocytes;
      HLA-independent pathogen-killing cells, and phagocytosis. Such cytokines as
      interferons, the TNF family, and interleukines 12 and 18 participate in
      antiviral, antibacterial, antiprotozoan and anticancer natural immunity. NK
      cells, cytokines of the TNF family, and the complement system activated by
      lectins are engaged in the non-specific killing of infected or tumor cells. As
      over-activation of the innate system can be dangerous, the system must be
      submitted the strict control. The exact mechanism of this control system is not
      yet known, but there are several indications of its presence.

PMID- 15995592
TI  - [Mitochondria as an source of reactive oxygen species].
AB  - Atmospheric oxygen molecules are reduced to water through four consecutive
      electron transfer reactions in mitochondria. As a consequence of these processes,
      various by-products (called reactive oxygen species, ROS), including superoxide
      radical, hydrogen peroxide, hydroxyl radicals, and singlet oxygen are released.
      Under physiological conditions, ROS are rapidly inactivated and do not induce
      disruption of cell function. Abnormal function of the respiratory chain,
      resulting from deficiency, mutation, or inhibition of its elements, leads to
      elevated ROS production. Complexes I and III of the mitochondrial chain are the
      most important sites of ROS formation; however, this can be affected by
      extracellular conditions. Excessive ROS generation leads to decreased efficiency
      of cells, tissues, and whole organs and is responsible for acceleration of aging
      and the development of various diseases.

PMID- 15995593
TI  - [Bacterial translocation and its clinical significance].
AB  - Bacterial translocation (BT) is defined as the passage of indigenous bacteria
      colonizing the intestine through the epithelial mucosa to the mesenteric lymph
      nodes and other sites. It can even cause the development of lethal sepsis. BT is
      being studied extensively, most research being conducted on animal, mostly
      murine, models. The cause of BT is not well known. Despite advances in
      antimicrobial therapy, the mortality rate associated with bacteremia is still
      high, and sepsis can often originate from the patient's own intestinal flora.
      Consequently, a better understanding of the mechanisms of BT as well as
      mechanisms operating to prevent bacteria from translocating from the
      gastrointestinal tract may provide more logical treatment of particular patients.
      BT may be promoted by immunosuppression (probably one of the most important
      factors causing the increase in BT), disturbances in the normal ecology of the
      gastrointestinal tract, allowing some indigenous bacteria to overgrow others, and
      by mucosal injuries. This article discusses the potential role of various factors
      responsible for BT and the relationship between BT and neoplastic disease. It
      also emphasizes the significance of the immune system, which appears to play a
      role in the ontogeny of gut-associated lymphoid tissue (GALT), including the role
      of IL-2 (which induces an increase in BT) and the macrophage, which participates
      in the transport of bacteria from the intestinal lumen to mesenteric lymph nodes.
      A better understanding of the immunopathology of BT may contribute to the
      development of novel means of therapy for sepsis and other serious complications
      of bacterial infection.

PMID- 15995594
TI  - [Modifications of actinomycin D structure as example of actinomycins structure
      activity relationship].
AB  - For over 60 years, actinomycins, well-known antibacterial and anticancer
      antibiotics, have been the subject of the scientific research. These compounds
      exhibit high toxicity and therefore are not widely used in the chemotherapeutic
      treatment of antibacterial and antifungal diseases. However, actinomycin D, the
      best-known compound from the actinomycin group, has been introduced into clinical
      practice as an anticancer drug. Actinomycin D, together with 7-amino-actinomycin
      D, also became a useful tool in biochemistry and molecular biology. The
      isolation, production, chemistry, and biological and clinical use of the
      actinomycins have been thoroughly investigated. Many derivatives of actinomycins,
      differing in chemical structure as well as biological activity, have been
      isolated and synthesized and their modifications involved not only the
      chromphoric phenoxazone ring, but also two cyclic pentapeptide lacton rings.
      Modifications of the actinomycins' chromophore mainly concerned introducing an
      amino group in position 2 and a carbon atom in position 7, but also modifications
      in positions 4, 6, and 8 of the phenoxazone ring. The actinomycin peptide moiety
      was mainly modified by replacement of amino acids in the pentapeptide rings and
      also by the synthesis of actinomycin derivatives with open peptide lacton rings.
      These modifications enabled separating the elements in the actinomycin structure
      which are responsible for the biological activity of these compounds. That was
      key information for recognizing the performance of these compounds, and an
      important way of planning effective new chemotherapeutics.

PMID- 15995595
TI  - [Metabolism of tryptophan via the kynurenine pathway in saliva].
AB  - In this review, the role of the kynurenine pathway enzymes TDO (tryptophan 2,3
      dioxygenase) and IDO (indoleamine 2,3 -dioxygenase) as well as the properties of
      the metabolites of kynurenine degradation present in human saliva described. The
      implications of these metabolites in the pathomechanism of tissue and organs
      dysfunction are demonstrated. The authors also describe at length the role of
      saliva kynurenine derivatives in the onset and development of periodontal disease
      in humans.

PMID- 15995596
TI  - [Actinomycin D and its mechanisms of action].
AB  - Actinomycin D is a well-known antibiotic of the actinomycin group that exhibits
      high antibacterial and antitumor activity. Actinomycin D has been widely used in
      clinical practice since 1954 as an anticancer drug for treating many tumors and
      it is also a useful tool in biochemistry and molecular biology. According to the
      Internet bibliographic database -- MEDLINE, actinomycins, and mainly actinomycin
      D, have been the subject of about 3300 science papers so far, and this paper is a
      review of the information concerning the mechanisms of action of actinomycin D.
      There are several mechanisms of its action that are responsible for its cytotoxic
      and antitumor action, these being associated with DNA functionality, leading to
      RNA and, consequently, protein synthesis inhibition. The two main mechanisms are
      intercalation to DNA and the stabilization of cleavable complexes of
      topoisomerases I and II with DNA, in which a phenoxazone ring localizes between
      GpC base pair sequence in DNA and polypeptide lactones rings occupy a position in
      the minor groove of the DNA helix or the drug penetrates to a place in the DNA
      structure where topoisomerase binds with DNA, respectively. Moreover, the slow
      dissociation of actinomycin D from DNA complexes, its photodynamic activity and
      free radical formation, as well as other biochemical effects of activity of
      actinomycin D may be, as suggested, important factors that influence the
      biological activity of this drug. In the literature not enough convincing
      evidence has been proposed that could indicate one particular mechanism of action
      as responsible for the biological activity of actinomycin D.

PMID- 15995597
TI  - [Muscle cell transplantations: the ups and downs].
AB  - Cell transplantation is believed to be an attractive technique among the various
      prospective methods of healing muscle wasting and other degenerative diseases.
      Muscle precursor cells can be obtained and cultured in vitro relatively easily,
      making possible a wide application of this method in the near future. A number of
      research efforts regarding cell transplantation for the recovery of dystrophic
      muscles and attempts to accelerate convalescence of disabled heart muscle are
      underway. There are also initiatives to use muscle cells in the repair of urinary
      incontinence. In the case of muscle dystrophy, very promising results were
      achieved in animal models, but the procedure has proved unreliable in clinical
      tests on humans. More convincing results were obtained from muscle cells
      transferred to myocardium. This procedure gave positive response in both animal
      models and clinical trials. However, there are still several obstacles to
      transplant muscle cells. First there is the poor viability of muscle cells after
      transfer. This results in sudden cell death, which occurs within a few hours
      after the cells are transferred to the recipient. A major concern recently is to
      develop procedures which will improve the efficacy of muscle cell
      transplantation. Growing interest is focused on autologous cell transplantation
      owing to the low immunogenicity of this kind of transfer. Moreover, numerous
      attempts are underway to suppress inflammation at the site of cell deposition or
      to search for subpopulations of cells which would result in a higher survival
      rate after transfer. Furthermore, genetic manipulations or preconditioning of
      muscle cells prior to transfer are often performed.

PMID- 15995598
TI  - [Therapeutic properties of proteins and peptides from colostrum and milk].
AB  - Colostrum and milk are rich in proteins and peptides which play a crucial role in
      innate immunity when transferred to the offspring and may accelerate maturation
      of the immune system in neonates. The immunotropic properties of these proteins
      prompted investigators research their potential application in prevention and
      therapy. Lactoferrin (LF) exhibits antibacterial, antifungal, antiviral,
      antiparasitice, and antitumoral activities. It is protective with regard to
      intestinal epithelium, promotes bone growth, and accelerates the recovery of
      immune system function in immunocompromised animals. LF was tried in the
      treatment of hepatitis C infection and the intestinal form of graft-versus-host
      disease (GvHD). A proline-rich polypeptide (PRP) demonstrated a variety of
      immunotropic functions, including the promotion of T-cell maturation and
      inhibition of autoimmune disorders. PRP, in the form of chewable tablets
      (Colostrinin) was recently found to improve or stabilize the health status of
      Alzheimer's disease patients. Casein and casein-derived peptides showed
      protective activities in enamel demineralization and as caries-preventing agents.
      The protein hydrolyzates were also protective in diabetic animals, reduced tumor
      growth, had antihypertensive activity and diminished colicky symptoms in infants.
      Glycomacropeptide (GMP), a peptide derived from kappa-casein, exhibited various
      antibacterial and antithrombotic activities. Alpha-lactalbumin (LA) demonstrated
      antiviral, antitumoral and anti-stress properties. LA-enriched diets were
      anxiolytic, lowered blood pressure in rats, prevented diarrhea, and led to a
      better weight gain in malnourished children. HAMLET, a complex of LA and oleic
      acid, was effective in patients with cutaneous papillomas. Lysozyme found
      application in infant formulas, the treatment of periodentitis, and the
      prevention of tooth decay. Milk enriched in lysozyme was used in feeding
      premature infants suffering from concomitant diseases. Interesting, antibacterial
      properties were exhibited by lactoperoxidase. Both lysozyme and lactoperoxidase
      required cooperative action with LF in combating bacteria. In conclusion,
      preparations derived from milk and colostrum are effective, easily bioaccessible,
      and safe, finding wide application in prevention and therapy for newborns and
      adults.

PMID- 15995599
TI  - [Publication of a special number of papers on radiological technology in relation
      to health science].

PMID- 15995600
TI  - [Current status and issues in cancer control strategy in Japan].

PMID- 15995601
TI  - [Status of radiological screening in the USA].

PMID- 15995602
TI  - [Effectiveness of mammographic screening and tasks of screening for breast cancer
      in Japan].

PMID- 15995603
TI  - [PET and Cancer Screening].

PMID- 15995605
TI  - [Process of development and spread of GE PET-CT].

PMID- 15995604
TI  - [The PET medical checkup considered from the viewpoint of radiological
      protection].

PMID- 15995606
TI  - [Clinical PET screening support service].

PMID- 15995607
TI  - [An assessment of the potential for interpretation of CT images by radiological
      technologists].

PMID- 15995608
TI  - [CAD for digital chest radiograph].

PMID- 15995609
TI  - [Mammography reading with CAD (computer aided detection): experiences and
      problems].

PMID- 15995610
TI  - [Development of real-time tissue elastography].

PMID- 15995611
TI  - [Handling of used medical devices].

PMID- 15995612
TI  - [Fractal analysis of trabecular architecture: with special reference to slice
      thickness and pixel size of the image].
AB  - Many analyses of bone microarchitecture using three-dimensional images of micro
      CT (microCT) have been reported recently. However, as extirpated bone is the
      subject of measurement on microCT, various kinds of information are not available
      clinically. Our aim is to evaluate usefulness of fractal dimension as an index of
      bone strength different from bone mineral density in in-vivo, to which microCT
      could not be applied. In this fundamental study, the relation between pixel size
      and the slice thickness of images was examined when fractal analysis was applied
      to clinical images. We examined 40 lumbar spine specimens extirpated from 16 male
      cadavers (30-88 years; mean age, 60.8 years). Three-dimensional images of the
      trabeculae of 150 slices were obtained by a microCT system under the following
      conditions: matrix size, 512 x 512; slice thickness, 23.2 em; and pixel size,
      18.6 em. Based on images of 150 slices, images of four different matrix sizes and
      nine different slice thicknesses were made using public domain software (NIH
      Image). The threshold value for image binarization, and the relation between
      pixel size and the slice thickness of an image used for two-dimensional and three
      dimensional fractal analyses were studied. In addition, the box counting method
      was used for fractal analysis. One hundred forty-five in box counting was most
      suitable as the threshold value for image binarization on the 256 gray levels.
      The correlation coefficients between two-dimensional fractal dimensions of
      processed images and three-dimensional fractal dimensions of original images were
      more than 0.9 for pixel sizes < or =148.8 microm at a slice thickness of 1 mm,
      and < or =74.4 microm at one of 2 mm. In terms of the relation between the three
      dimensional fractal dimension of processed images and three-dimensional fractal
      dimension of original images, when pixel size was less than 74.4 microm, a
      correlation coefficient of more than 0.9 was obtained even for the maximal slice
      thickness (1.74 mm) examined in this study.

PMID- 15995613
TI  - [Physical property of emission data in simultaneous emission/transmission
      acquisition: evaluation for clinical application].
AB  - PURPOSE: Although simultaneous emission transmission acquisition (SET) is the
      ideal method for positron emission tomography (PET) because the same patient
      position can be used for both emission and transmission scans, the quality of PET
      images is subject to interference by the cross-contamination of each data. In
      recent years, segmented attenuation correction of transmission data has made it
      possible to exclude the contamination from emission data. In the present study
      using a phantom, the physical property of emission data in SET acquisition was
      evaluated in comparison with that in separate scan. METHODS: We measured scatter
      fraction, scatter projection, % random, and noise equivalent count rate in the
      sinogram. Next, we determined the acquisition time of the SET scan to obtain the
      same coefficient of variation as the separate scan in reconstructed images.
      RESULTS: In the evaluation of the strength of the line source, the physical
      property of emission data in the SET scan seemed inferior to that in separate
      scan, and SET scanning was not effective enough to reduce the acquisition time of
      PET examinations. CONCLUSION: SET scanning has the advantage that the same
      patient position can be used for emission and transmission data; however, further
      studies may be necessary to apply it to clinical examinations.

PMID- 15995614
TI  - [CR-mammography with pixel size of 50 microm and dual-sided reading system:
      effect of the oblique incident of the X-ray beam on imaging properties and
      detection].
AB  - In mammography units, the X-ray tube focal spot is located directly above the
      chest wall edge of the detector. Therefore, the X-ray beam is incident at a
      different angle along the cathode-anode axis. When the X-ray beam is incident on
      the imaging plate (IP) at a relatively large angle, the resolution property of a
      new imaging plate with dual-sided reading system would be degraded compared with
      the conventional imaging plate because of the parallax effect, which produces a
      shift in the image on two sides of the imaging plate. To evaluate the oblique
      incidence effect of the X-ray beam on the degradation of resolution properties
      and detection of simulated microcalcifications of a new CR system with a pixel
      size of 50 microm, its basic imaging properties and observer performance tests
      were compared with those of a conventional CR system. The resolution properties
      were evaluated by measuring modulation transfer functions (MTFs). Observer
      performance tests were conducted to compare the detectability of simulated
      microcalcifications of CR systems. Degradation of presampling MTFs for the new
      system is greater than that of the conventional CR system when the X-ray beam was
      incident at the same angle on the imaging plate. We found that the degradation of
      the area under the ROC curve (Az) for the new CR system was greater than that of
      the conventional CR system when the X-ray beam was incident at the same angle on
      the imaging plate.

PMID- 15995615
TI  - [Evaluation of Intra-abdominal fat distribution using X-ray CT data for detection
      of rectal cancer].
AB  - To develop a novel method of detecting rectal cancer, we assessed relationships
      between intra-abdominal fat distribution and rectal cancer in Japanese patients.
      Subjects comprised 38 patients with rectal cancer apparent on CT-colonography and
      110 other cases. The intra-abdominal fat area was determined by calculating pixel
      distribution with attenuation values from -140 HU to -40 HU. The area of intra
      abdominal fat was measured on axial images using an interslice gap of 10 mm.
      Profile curves of intra-abdominal fat were in the plane direction from diaphragm
      to anus. Of note is the fact that Ogura's peak, a secondary small peak around the
      rectal cancer, was apparent on the profile of intra-abdominal fat, with 73.7% of
      rectal cancers displaying Ogura's peak. In comparison, only 19.1% of other cases
      displayed Ogura's peak on this profile. The relationship between fat and rectal
      cancer is difficult to explain. However, making good use of these results showing
      intra-abdominal fat distribution, a computer-aided diagnosis (CAD) system for
      detecting rectal cancer according to the presence of Ogura's peak has potential
      as a method of mass screening. As only 148 cases were investigated in the present
      study, the accumulation of additional data is needed. More detailed studies with
      larger patient populations are warranted.

PMID- 15995616
TI  - [Present status and issues regarding X-ray medical checkup vehicles in preventive
      medicine: usefulness of mass screening for lung cancer by an X-ray medical
      checkup vehicle].
AB  - Although the prevention of habituation-related diseases has become an important
      topic in Japan, the early detection of cancers such as lung, gastric, and breast
      cancers is an important issue for X-ray-related imaging modalities. High cost
      benefit and cost-effectiveness are necessary to perform mass screenings such as
      those for lung cancer. In order to assess cost-benefit and cost-effectiveness, a
      total of 100 institutions nationwide were investigated, with a 41% of recovery
      rate. There were at least one or two institutions in each prefecture. Cost
      benefit analysis was based on factors including the price of the medical check-up
      vehicle, its service life, and income from the examinations. The mean price of
      medical check-up vehicles used for chest X-ray examinations was 4,445,000 yen.
      Cost-effectiveness analysis was based on the expense incurred to discover one
      lung cancer. According to our research, the cost-effectiveness involved in
      detecting one lung cancer by conventional chest X-ray examination was about
      2,270,167 yen/person. Since this amount seems unduly high, it is necessary to
      improve cost-effectiveness.

PMID- 15995617
TI  - [Study of the usefulness of large intestine screening inspections using multi
      slice CT (MSCT)].
AB  - CT-colonography (CT-C), a new diagnostic imaging technique for cancer of the
      large intestine--which is increasing rapidly owing to westernized eating habits-
      has advanced from the developmental stage to the stage of practical application,
      thanks to progress in MSCT and workstation development. Therefore, based on the
      results of CT-C application using 16 lines of MSCT to a screening test, we
      reviewed the usefulness of CT-C in our clinic. We supplemented defective
      depiction, and found that change of position was effective for virtual image
      exclusion. We consider that CT-C can support diagnosis if the target of screening
      tests is a polypoid lesion of more than 6 mm. In addition, it is expected that
      the number of examinations performed during office visits will increase because
      of the decreased invasiveness of the procedure, its lack of pain, and its ability
      to provide early lesion detection.

PMID- 15995618
TI  - [Current situation and problems of PET examinations].
AB  - In recent years, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)
      has become a remarkable new modality for use in preventive medicine. FDG-PET
      examinations have many characteristics that are not available through
      conventional examinations, including the diagnosis of cancer. However, devices
      and examination techniques that take advantage of the merits of FDG-PET
      examinations are still required. In addition, many problems related to the
      management of facilities need to be solved. Therefore, we introduce the current
      situation of FDG-PET examinations in our facility and discuss our problem-solving
      efforts. FDG-PET examinations are very useful as screening examinations for
      cancer, and, in the future, FDG-PET will combine with other techniques and
      examinations in preventive medicine to provide a general cancer-screening system.
      For the future development of FDG-PET, we need to focus on the effective
      utilization of FDG-PET examinations and to establish evidence of their
      effectiveness. Moreover, we must create guidelines for the improvement of
      technology and the standardization of PET examination facilities.

PMID- 15995619
TI  - [Ultrasonographic study of the hip joint in infants].
AB  - We performed ultrasonography screening for the hip joint in 145 infants between
      January 2003 and January 2004 at Nakajo-machi in Niigata Prefecture. This
      ultrasonographic study was conducted by Graf's method. The method could
      discriminate normal hip joints and was able to visualize 11 abnormal hip joints
      as well. All abnormal hip joints were dysplastic. This method is more useful than
      x-ray examination for infants, since the cartilaginous femoral head and the soft
      tissues around the hip could be clearly visualized. As a result, ultrasonography
      appears to be a useful screening method for congenital dislocation of the hip
      joint, without the hazard of radiation caused by x-rays.

PMID- 15995620
TI  - [Screening for lung cancer by low-dose computed tomography].
AB  - The primary screening method for lung cancer in Japan is the chest x-ray,
      although it is not the accepted international standard because its accuracy is
      lower than that of procedures used to detect other types of cancer. Since the
      incidence and mortality rate of lung cancer are higher than in many other
      cancers, more effective screening modalities need to be developed. Lung cancer
      screening was improved about ten years ago through the introduction of computed
      tomography (CT) scanning techniques. CT provides a higher level of accuracy in
      detecting early lung cancers and there have been reports of improvement in the
      five-year survival rate, although its effect on decreasing the mortality rate has
      not been demonstrated as yet. There are two significant disadvantages, however,
      associated with using CT for the detection of lung cancer. First, CT scanning
      results in a considerably higher level of radiation exposure than chest x-ray.
      Secondly, CT scanning is so sensitive that it can reveal shadows unrelated to
      lung cancer, resulting in additional, but unnecessary CT scans being performed
      for further examination. Accordingly, this report reviews the basic points that
      should be considered when conducting CT scanning for lung cancer screening
      purposes.

PMID- 15995621
TI  - [Current situation and future of gastric cancer screening examinations: from the
      viewpoint of gastric X-ray screening].
AB  - In Japan, screening examinations for gastric cancer have been conducted for 50
      years because of the high prevalence of this type of cancer. Gastric X-ray
      screening examinations have contributed to the detection early gastric cancer. In
      2001, Hisamichi et al. reported that X-ray examination is a valid technique in
      gastric cancer screening. However, they indicated that problems in the
      uncertainty of accuracy and the risk of radiation exposure at a young age. On the
      other hand, endoscopic screening examination, pepsinogen-method and H. pylori
      method are not acceptable because of incident risk. Our future goals are to
      improve the precision of gastric X-ray examinations in cancer screening
      nationwide and to advocate for annual gastric screening examinations in higher
      risk groups. As a result, it is hoped that gastric cancer X-ray screening
      examinations can contribute to preventive medicine.

PMID- 15995622
TI  - Integrins adhesion molecules and some of their ligands in laryngeal cancer.
AB  - In this review data regarding the regular expression and distribution of
      integrins adhesion molecules as well as some of their ligands in cases of
      squamous cell carcinoma of the larynx (LSCC) are discussed. Cancer of the larynx
      is one of the most common malignancies of the head and neck. Upon neoplastic
      transformation several alterations of the integrins adhesion molecules and
      extracellular matrix (ECM) components are observed, i.e. the loss of the normal
      architecture especially depolarization of some integrins, like alpha6beta4,
      alpha3beta1, alpha2beta1 as well as the presence of alpha6beta1 integrin in
      neoplastic epithelium. Furthermore, the upregulation of alpha5beta1 integrin is a
      negative prognostic factor. In cases of laryngeal cancer, disorganization of the
      basal membrane components (laminins 1 and 5, type IV collagen, tenascin,
      fibronectin isoforms) which represent integrins ligands, is found. This is due to
      partial or complete destruction of the basal membrane, thus, permitting
      extravasation and migration of cancer cells. These phenomena are observed in a
      greater degree in tumors showing poor prognosis. It seems that damage of these
      adhesion complexes is important in the neoplastic process. So, further studies
      are necessary to establish the importance of these markers to early larynx cancer
      diagnosis and reach the decision on appropriate therapeutic strategies in the
      management of those patients.

PMID- 15995623
TI  - Combined use of antisense oligonucleotides and chemotherapeutics in the treatment
      of refractory prostate cancer.
AB  - Throughout the past six decades, our understanding of cancer of the prostate and
      the treatment of the disease using endocrine therapy has been centred on the
      classical investigations of Charles Huggins, which established that tumor tissue
      of the prostate as well as the normal tissue of the gland retained some degree of
      androgen dependence. Attention must now be focussed on the 20-40% of patients who
      are resistant to endocrine therapy. These patients are non-responders to
      conventional endocrine treatment after 3 to 6 months, quickly progress and die of
      the disease. In terms of molecular endocrinology related to the progressive stage
      of the disease, it would be expected that the cancer is being driven by the
      uncontrolled action of growth factors. Experiments combining oligonucleotide
      treatment with cytotoxic chemotherapeutic agents demonstrated a marked increase
      in the sensitivity of the prostate cancer cells. Results indicate that despite
      the presence of Bcl-x pre-mRNA in a number of cell types, the effects of
      modification of its splicing by antisense oligonucleotides vary depending on the
      expression profile of the treated cells. The transition from androgen-dependent
      to androgen non-dependent prostate cancer is accompanied by a number of molecular
      genetic changes, including overexpression of the Bcl-2 gene. Overexpression of
      Bcl-2 protein decreases the pro-apoptotic response to such cellular insults as
      irradiation, chemotherapy, and androgen withdrawal. The future looks promising
      and this kind of treatment offers a novel approach to alternative therapeutic
      options for advanced prostate cancer. Although numerous chemotherapeutic regimens
      have been evaluated for patients with hormone-refractory prostate cancer, none
      has improved survival.

PMID- 15995624
TI  - Mediterranean and Black Sea organisms and algae from mariculture as sources of
      antitumor drugs.
AB  - Mussels and tunicates cultivated in Mediterranean and Black Sea are the sources
      of antitumor drugs. Three compounds isolated from these animals (ET-743, aplidin
      and bryostatin-1) are on the II-III stages of clinical trials. Carotenoid
      fucoxantin that is present in edible brown algae possesses antitumor activity.
      The consumption of brown macrophyts decreases the risk of cancer development.

PMID- 15995625
TI  - Epstein-Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via
      regulating expression of Survivin in nasopharyngeal carcinoma.
AB  - Pathways controling cell proliferation and cell survival require flexible
      adaptation to environmental stress. Our previous studies showed that latent
      membrane protein1 (LMP1) encoded by Epstein-Barr virus (EBV) could trigger the
      expression of Survivin, an apoptosis inhibitor and essential regulator of
      mitosis. The aim of the work was to analyze the role of Survivin signal pathway
      in mediating effects triggered by LMP1. METHODS: Tet-on LMP1 HNE2, a tetracycline
      regulated LMP1-expression nasopharyngeal carcinoma cell line, was used as cell
      model. The subcellular location of Survivin was detected by indirect
      immunofluorescence and Western-blotting assay. Using Ab-knock-out and gene
      transfection, we introduced anti-sense PS-ODN-Survivin and anti-body to Survivin
      into the Tet-on LMP1 HNE2, and then the apoptosis and the proliferation of cells
      were analyzed by flow cytometry, cell colony formation and detection of caspase
      3. The results show that upon induction of LMP1 expression, the expression of
      Survivin in nucleus, level of phosphorylated retinoblastoma gene (Rb), the number
      of cells in S stage of cell cycle, and the cell colony formation rate were higher
      than those without LMP1 induction; if the expression of Survivin and the nucleus
      translocation of Survivin were knocked by introduction of anti-sense PS-ODN
      Survivin and anti-Survivin-antibodies respectively, apoptosis rates and the
      activity of caspase-3 increased. CONCLUSION: LMP1 could trigger the nucleus
      translocation of Survivin, which led to the shift of S stage and cell
      proliferation. LMP1 may promote cell proliferation and inhibits apoptosis via
      Survivin signal pathway.

PMID- 15995626
TI  - Radiation-induced DNA-damage and gene expression profiles in human lung cancer
      cells with different radiosensitivity.
AB  - BACKGROUND: Measurements of DNA double strand breaks and their subsequent repair
      after in vitro irradiation has been suggested to be an alternative way of
      monitoring radiotherapeutic response. METHODS: In the present study, the DNA
      repair kinetics (using a neutral version of the Comet assay) up to 45 min after a
      single dose of 2 Gy was studied as well as the gene expression profiles, before
      and 45 min after the irradiation, in two human lung cancer cell lines with
      different radiosensitivity (U-1285 and U-1810). RESULTS: Immediately after the
      irradiation, both cell lines responded with increased levels of DNA damage.
      However, the induced damage was slightly higher in U-1810 (known to be
      radioresistant) than in U-1285 (known to be radiosensitive), and the latter cell
      line also seemed to have a slightly more efficient DNA-repair. The two different
      lung cancer cell lines were highly heterogeneous in gene expression, both before
      and after the irradiation, and there was no obvious relationship between the
      Comet data and the microarray data. CONCLUSION: Given the fact that U-1810 has
      been classified as radioresistant and U-1285 as radiosensitive in clonogenic
      assays, the results of the present study indicate that radiation-induced DNA
      double strand breaks and DNA-repair efficiency are poor indicators of the
      intrinsic radiosensitivity of human lung cancer cells irradiated with a single
      dose in vitro.

PMID- 15995627
TI  - PGE2 up-regulates vascular endothelial growth factor expression in MKN28 gastric
      cancer cells via epidermal growth factor receptor signaling system.
AB  - AIM: 1) To evaluate the effect of prostaglandin E2 (PGE2) on the regulation of
      vascular endothelial growth factor (VEGF) expression in gastric MKN28 cells, and
      2) to investigate the role of the epidermal growth factor receptor (EGFR) signal
      transduction pathway in any effect exerted by PGE2 on VEGF expression. METHODS:
      MKN28 cells were incubated with the vehicle (control) or with PGE2 in the
      presence or absence of AG1478, a selective inhibitor of EGFR tyrosine kinase, or
      PD098059, a selective inhibitor of the kinase responsible for ERK2
      phosphorylation (mitogen-activated protein (MAP)/extracellular signal-regulated
      kinase (ERK)). Real-time quantitative polymerase chain reaction and Western blot
      analysis were used to evaluate VEGF mRNA and protein expression. The activity of
      EGFR and ERK2 was measured by Western blot analysis. RESULTS: PGE2 significantly
      up-regulated VEGF mRNA and protein expression and increased the activation of
      EGFR and ERK2. Incubation of MKN28 cells with AG1478 significantly reduced PGE2
      induced EGFR activity, ERK2 activity, and VEGF mRNA and protein expression.
      Meanwhile, incubation of MKN28 with PD098059 reduced PGE2-induced ERK2 activity
      and VEGF mRNA and protein expression, but had no effect on EGFR activity.
      CONCLUSION: Our data suggested that PGE2 up-regulates VEGF expression in gastric
      cancer cells via transactivation of EGFR-MAPK signaling pathways, which may be
      mechanisms underlying the contribution of COX-2 to tumor angiogenesis in gastric
      cancer.

PMID- 15995628
TI  - Genetic variability of the mouse hepatoma cells MH-22a revealed by RAPD-PCR
      fingerprinting under different conditions of cultivation.
AB  - AIM: to study genetic variability in clonal lines of the mouse hepatoma MH-22a
      and the dependence of the capability of different clonal line cells for
      differentiation on the amount of genetic disturbances revealed by the RAPD-PCR
      method. METHODS: The hepatoma MH-22a and its ten clonal lines were transplanted
      into subcutaneous connective tissue (SCT) and the eye anterior chamber (EAC) by
      injection of the cells to syngenic C3HA mice. The growth of transplants was
      checked in 15-20 days after transplantation. The tumors were fixed in neutral
      paraformaldehyde (10%), passed through ethanol of increasing concentrations,
      embedded in paraffin and stained by hematoxiline and eosine and Van Gisone. The
      genetic heterogeneity in the hepatoma cell population MH-22a and its clonal lines
      in vitro and in vivo was revealed by random amplified polymorphic DNA (RAPD-PCR).
      For the estimation of genetic variability revealed in the fingerprints was used
      the genetic variability index (GVI), based on the Bootstrep and Mikulinskaya's
      statistic programme. RESULTS: The comparative analysis of the genetic structure
      of the clonal line populations in vitro and in vivo has revealed that the amount
      of clones with the high, intermediate, and low variability is approximately the
      same in both cases. It was also shown that GVI in various clonal lines in vitro
      correlated with their vital ability: the clones yielding clone lines had the
      lowest GVI. The same GVI value was found in the clonal lines proliferated in the
      EAC regardless of their capability for differentiation. Intraclonal analysis has
      shown that the highest values of changes revealed on fingerprints of the
      amplification of DNA products do not prevent from differentiation of tumor
      hepatoma cells in the EAC. CONCLUSION: These data allow concluding that the mouse
      hepatoma cells MH-22a can preserve ability for differentiation in spite of
      significant changes in their genome.

PMID- 15995629
TI  - Wortmannin elevates tumor necrosis factor-related apoptosis-inducing ligand
      sensitivity in LNCaP cells through down-regulation of IAP-2 protein.
AB  - BACKGROUND AND AIM: TNF-related apoptosis-inducing ligand (TRAIL), which is a
      member of the tumor necrosis factor (TNF) family, has been shown to effectively
      induce tumor apoptosis without any detectable cytotoxic side effects. But recent
      studies have shown that LNCaP cells are resistant to TRAIL, because LNCaP cells
      express the constitutively active Akt/protein kinase B. Therefore this study
      examined the effect of Wortmannin, a PI-3 kinase inhibitor, and the intracellular
      mechanisms to TRAIL-induced apoptosis. METHODS: LNCaP cells, which are resistant
      to apoptotic induction of TRAIL alone, were exposed to Wortmannin for 3 h and
      treated with the recombinant TRAIL protein for an additional 3 h. RESULTS: TRAIL
      alone induced apoptosis in approximately 10% of the cells, whilst pretreatment
      with Wortmannin increased the TRAIL-induced apoptosis to 45%. Wortmannin alone
      had no effect on the tumor cell viability, but enhanced the TRAIL-induced
      apoptosis in a dose-dependent manner and completely blocked Akt phosphorylation.
      The blocking of the Akt phosphorylation decreased the IAP-2 protein expression
      level, which is believed to mediate the enhanced TRAIL-induced apoptosis.
      CONCLUSION: Wortmannin elevates the TRAIL sensitivity in LNCaP cells by
      regulating the phosphorylation of Akt and IAP-2 protein expression.

PMID- 15995630
TI  - Increased susceptibility of tumorigenicity and decreased anti-tumor effect of DC
      vaccination in aged mice are potentially associated with increased number of
      NK1.1+CD3+ NKT cells.
AB  - AIM: It is established that aging leads to declines in immune function. However,
      the mechanisms underlying remain poorly understood. METHODS: In this study, we
      compared the tumoriginecity of MO4 (ovalbumin-transfected) tumor cells, the
      efficacy of dendritic cell (DC) vaccination and cytotoxic T lymphocytes (CTLs),
      and the number of NK1.1+CD3+ NKT cells between aged mice and young mice using T
      cell proliferation and cytotoxicity assays and flow cytometry. RESULTS: We showed
      that, in comparison to young mice, aged mice are 10-fold more susceptible to
      tumorigenicity of MO4 tumor cells. Aged mice immunized with bone marrow-derived
      DCs pulsed with ovalbumin (DCOVA) survived significantly shorter after challenge
      with MO4 tumor cells as compared to equally treated young mice. Furthermore, CTLs
      from aged mice immunized with DCOVA displayed 4-fold weaker cytotoxicity as
      compared to CTLs from immunized young mice. Interestingly, the number of
      NK1.1+CD3+ NKT cell significantly increase with aging (p < 0.05). Of particular
      importance, NK1.1+CD3+ NKT cells isolated from aged mice suppress the
      proliferation of T cells. CONCLUSIONS: Based on these data, we conclude that
      NK1.1+CD3+ NKT cells from aged mice mediate immunosuppression, and further
      suggest that increased number of NK1.1+CD3+ NKT cells in aged mice might, among
      others, diminish their immune function by mediation of immunosuppression.

PMID- 15995631
TI  - Expression of beta-defensin-2 in human gastric tumors: a pilot study.
AB  - The present work was AIMED on the study of patterns of human beta-defensin-2 (hBD
      2) expression in human gastric tumors. MATERIALS AND METHODS: 17 samples of
      surgically resected human gastric adenocarcinoma paired with respective normal
      tissue controls have been analyzed for the expression of hBD-2 by semi
      quantitative RT-PCR and by immunohistochemical analysis using anti-hBD-2
      monoclonal antibodies (mAbs) generated against recombinant hBD-2 by standard
      hybridoma technology. RESULTS: The hyperexpression of hBD-2 on mRNA and protein
      levels was registered in 6 from 17 gastric tumor samples compared to respective
      controls; however, hBD-2 expression patterns seems not be related to the
      differentiation grade and stage of tumors and the presence of anti-Helicobacter
      pylori-antibodies in the blood serum of the patients. CONCLUSION: In human
      gastric adenocarcinomas expression of hBDs possesses heterogeneic character; the
      research on larger cohort of the patients with gastric cancer should be further
      performed.

PMID- 15995632
TI  - IgG immune response to tumor-associated carbohydrate antigens (TF, Tn, alphaGal)
      in patients with breast cancer: impact of neoadjuvant chemotherapy and relation
      to the survival.
AB  - AIM: To study the humoral immune response to tumor-associated carbohydrate
      epitopes (TF, Tn and alphaGal) in patients with breast cancer and healthy donors,
      the putative impact of the chemotherapy and to evaluate if the level of antibody
      to these epitopes might be beneficial or detrimental for the patients with breast
      cancer. MATERIALS AND METHODS: The humoral immune response to TF, Tn and alphaGal
      was studied in 133 patients with breast cancer, including the patients at stage
      II-III (n = 44) before and after neoadjuvant chemotherapy (10 patients received
      cyclophosphamide/methotrexate/fluorouracyl (CMF) chemotherapy regimens, 34
      patients received cyclophosphamide/doxorubicin/fluorouracil (CAF)), and in
      controls (healthy donors and patients with fibroadenoma). Fully synthetic
      carbohydrate hapten-polyacrylamide conjugates were used as antigens in ELISA for
      anti-carbohydrate antibody determination. The correlation analysis between the
      level of anti-carbohydrate antibodies and the stage of cancer, histological
      grade, expression of TF and alphaGal epitopes in tumor tissue, patient's survival
      was performed. RESULTS: The level of anti-carbohydrate antibodies varied between
      individuals with no significant correlation between IgG immune response to the
      three epitopes. Lower levels of antibodies were observed at advanced stages of
      cancer. Neoadjuvant chemotherapy stimulated antibody production to Tn and
      alphaGal epitopes (increase > 50%) in about one third of patients.
      Immunosuppression, decrease in antibody levels, was observed only in 4.5-13.6% of
      cases. High levels of TF-antigen specific IgG antibody before surgery were
      associated with a better survival time of stage II breast cancer patients.
      CONCLUSION: The widely used regimens of neoadjuvant chemotherapy (such as CMF,
      CAF) can stimulate the immune response to tumor-associated carbohydrate epitopes
      in some patients. The high levels of anti-TF antibody before surgery are
      associated with a better survival of stage II breast cancer patients. This may
      indicate that the selection of immunopotentiating regimens of neoadjuvant
      chemotherapy might be beneficial for the host.

PMID- 15995633
TI  - Immunohistochemical analysis of Ki-67, PCNA and S6K1/2 expression in human breast
      cancer.
AB  - AIM: To assess the correlation between the expression profiles of ribosomal
      protein S6 kinase (S6K1/2), Ki-67 nuclear antigen (Ki-67) and proliferating cell
      nuclear antigen (PCNA) in human breast adenocarcinomas. METHODS: The expression
      pattern of S6K1/2, Ki-67 and PCNA has been investigated by immunohistochemical
      analysis of formalin fixed paraffin embedded sections of 40 human breast
      adenocarcinomas. Analysis was performed using specific monoclonal and polyclonal
      antibodies directed against S6K2, Ki-67 and PCNA followed by semi-quantitative
      measurements. RESULTS: Positive correlation between nuclear staining for S6K2 and
      PCNA (p < or = 0.01) or Ki-67 (p < or = 0.01) in breast cancer cells has been
      detected. No significant correlation in nuclear staining was observed between
      S6K1 and PCNA or Ki-67. In addition, we have detected an increase in S6K2
      expression in the nuclei of cancer cells localized predominantly in peripheral
      areas of the tumor contacting with normal tissue. CONCLUSION: The accumulation of
      S6K2, but not S6K1, in the nuclei of cancer cells and the correlation with the
      expression of PCNA and Ki-67 suggest the involvement of S6K2 in the regulation of
      malignant growth.

PMID- 15995634
TI  - Association of HER-2/neu overexpression with the number of involved axillary
      lymph nodes in hormone receptor positive breast cancer patients.
AB  - AIM: To evaluate the prognostic significance of HER-2/neu overexpression in
      hormone receptor and axillary lymph node positive breast cancer patients treated
      in a single institution. METHODS: Paraffin-embedded primary breast cancers from
      40 patients with invasive ductal carcinoma were studied immunohistochemically.
      HER-2/neu staining was classified as negative (0, 1+), weak/moderate positive
      (2+), or moderate/strong positive (3+) and was assessed for effectiveness as a
      predictor of outcome in univariate and Cox model multivariate analyses. RESULTS:
      20% of patients were positive for HER-2/neu. Significant associations were
      observed between HER-2/neu and increasing number of involved nodes (p = 0.014),
      p53 positivity (p = 0.039), the presence of vascular invasion (p = 0.029) and
      metastases (p = 0.01). Multivariate analysis demonstrated that HER-2/neu
      overexpression (p = 0.016) and age (p = 0.005) were independent predictors for
      disease-free survival (DFS) where the number of involved nodes (p = 0.032) was
      shown to be independent predictor for overall survival. In the HER-2/neu
      positively stained tumors, significant number of patients developed distant
      metastases than the patients with HER-2/neu negatively stained tumors (87.5% vs
      34.4%, p = 0.01). CONCLUSION: For node positive patients, HER-2/neu
      overexpression was a significant predictor of DFS.

PMID- 15995635
TI  - Hierarchy of treatment variables affecting outcome of 131I therapy in thyroid
      cancer patients with lung metastases.
AB  - AIM: To assess the correlations between the first 131I activity value, time
      interval between the courses of radioiodine treatment and the overall number of
      courses required for total destruction of lung metastases in patients with
      differentiated thyroid cancer with metastatic lesions in lungs. METHODS: 27
      patients with differentiated thyroid cancer with metastases in lungs have been
      treated with radioiodine after surgical intervention. Activities administered
      amounted from 1600 to 7980 MBq. The number of radioiodine courses before total
      ablation of all metastatic lesions amounted from 1 to 10. Time interval between
      the 1st and the 2nd courses amounted from 3.5 to 11.5 months (6 months in
      average). The regression analysis of the data has been made. RESULTS: The
      exponential model fits the actual number of courses as a function of the first
      second activity value and time interval between the courses. The first activity
      has a decisive influence on the number of courses required for total metastases
      ablation. The greater was the first activity value, the lesser was the overall
      number of courses. Increasing time interval between 1st and 2nd courses to 10
      months seems to result in reducing the number of courses. Nevertheless even in
      the case of high activities the probability to undergone less then 3 courses is
      low. According to the proposed model in thyroid cancer patients with metastases
      in lungs the first activity should be not lesser than 6000 MBq, time interval
      between treatments--approximately 10 months. CONCLUSION: The results of our study
      suggest that individual factors such as histology, the number and the size of
      metastases in lymph nodes could not contribute more to the final outcome than the
      treatment variables, namely the first-second activity and time interval, nor
      could they affect the hierarchy of the effects revealed for the treatment
      variables.

PMID- 15995636
TI  - Expression of mRNA coding for TGF-beta and its receptors in irradiated human
      breast carcinoma MCF-7 cells differing in their sensitivity to doxorubicin.
AB  - AIM: The effect of X-irradiation on the expression of mRNAs coding for
      transforming growth factor beta (TGF-beta) and its receptors was compared in
      human breast carcinoma MCF-7 cells differing in their sensitivity to doxorubicin.
      METHODS: Semiquantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) was used for the estimation of mRNAs expression for TGF-beta1, TGF-beta2 and
      TGF-beta type I and II receptors in the unirradiated and irradiated cells of two
      sublines of MCF-7 cells--sensitive (MCF-7(wt)) and resistant (MCF-7(DOX/R)) to
      doxorubicin. RESULTS: X-irradiation caused an increase in TGF-beta1 coding for
      mRNA expression in both breast cancer cell lines tested and an elevation of TGF
      beta2 mRNA expression in doxorubicin-resistant subline. The down-regulation of
      TGF-beta type I and II receptors in the irradiated MCF-7(DOX/R) cells was
      revealed at the transcriptional level. CONCLUSIONS: The results of our study show
      that the development of refractoriness of used tumor cells to anti-cancer drug
      doxorubicin, at least partly, can be caused by the impairment in TGF-beta
      signaling pathway.

PMID- 15995637
TI  - Phenotypic APC resistance as a marker of hypercoagulability in primitive cerebral
      lymphoma.
AB  - Thrombosis is the most frequent complication and the second cause of death in
      patients with malignant disease. Primary central nervous system non-Hodgkin's
      lymphoma represents a rare pathology. Resistance to APC is usually linked to a
      factor V (FV) gene mutation changing an Arg 506 to a Gln in the APC cleavage
      site. AIM: In our study, we aimed at investigating the presence of activated
      protein C resistance (APC-r) and other markers of hypercoagulability in 25
      selected patients with a diagnosis of primitive cerebral lymphoma who had
      suffered from an ischemic episode of TIA and/or stroke. PATIENTS AND METHODS: 25
      selected patients with a diagnosis of primitive cerebral lymphoma and 50 healthy
      subjects acted as control group, were tested. We measured APC-r, natural clotting
      inhibitors, F1 + 2, aPTT and PAI-1 according to international guidelines. Genomic
      DNA was extracted from peripheral white blood cells and in order to detect FV
      Leiden gene polymorphism. RESULTS: Our results showed that 11 out of 25 patients
      had a poor response to APC (< or = 0.70, which represents the cut-off point in
      our general population) without deficiencies in natural clotting inhibitors. All
      patients had high plasma levels of F1+2 and PAI-1 compared to those found in
      healthy subjects (2.65 +/- 0.75 nM/L vs 0.40 +/- 0.35 nM/L; 67.5 +/- 18.5 ng/mL
      vs 17 +/- 11.5 ng/mL, respectively). In 9 patients resistance to APC was not
      associated to a FV gene defect demonstrating that such phenomenon may occur also
      as an acquired condition. However, the patients with resistance to APC showed the
      highest plasma values in F1 + 2 and PAI-1. CONCLUSION: In cerebral lymphoma with
      hypercoagulability the resistance to APC is not caused by the FV Arg 506-->Gln
      mutation (82%). APC resistance not caused by this FV gene defect may be an
      additional risk factor for thrombophilia in this selected population.

PMID- 15995638
TI  - Isolation and characterization of bacteria associated with two sand dune plant
      species, Calystegia soldanella and Elymus mollis.
AB  - Little is known about the bacterial communities associated with the plants
      inhabiting sand dune ecosystems. In this study, the bacterial populations
      associated with two major sand dune plant species, Calystegia soldanella (beach
      morning glory) and Elymus mollis (wild rye), growing along the costal areas in
      Tae-An, Chungnam Province, were analyzed using a culture-dependent approach. A
      total of 212 bacteria were isolated from the root and rhizosphere samples of the
      two plants, and subjected to further analysis. Based on the analysis of the 16S
      rDNA sequences, all the bacterial isolates were classified into six major phyla
      of the domain Bacteria. Significant differences were observed between the two
      plant species, and also between the rhizospheric and root endophytic communities.
      The isolates from the rhizosphere of the two plant species were assigned to 27
      different established genera, and the root endophytic bacteria were assigned to
      21. Members of the phylum Gammaproteobacteria, notably the Pseudomonas species,
      comprised the majority of both the rhizospheric and endophytic bacteria, followed
      by members of Bacteroidetes and Firmicutes in the rhizosphere and
      Alphaproteobacteria and Bacteroidetes in the root. A number of isolates were
      recognized as potentially novel bacterial taxa. Fifteen out of 27 bacterial
      genera were commonly found in the rhizosphere of both plants, which was
      comparable to 3 out of 21 common genera in the root, implying the host
      specificity for endophytic populations. This study of the diversity of culturable
      rhizospheric and endophytic bacteria has provided the basis for further
      investigation aimed at the selection of microbes for the facilitation of plant
      growth.

PMID- 15995639
TI  - Highland macrolichen flora of Northwestern Yunnan, China.
AB  - Fifty-six species in 36 genera of macrolichens are reported from the Zhongdian
      area, northwest Yunnan, China during the lichenological expedition for highland
      macrolichen survey in June, 2004. More than 60% of these species have not been
      reported in South Korea. All of the 182 collected specimens are deposited in the
      Korean Lichen Research Institute (KoLRI) at Sunchon National University in Korea,
      and some of them are duplicated in the lichen herbarium, Crytogamic Herbarium,
      Kunming Institute of Botany, Academia Sinica (KUN-L) in China. This is the first
      report on the macrolichen flora in the visited areas.

PMID- 15995640
TI  - Characterization of calcium-activated bifunctional peptidase of the
      psychrotrophic Bacillus cereus.
AB  - The protease purified from Bacillus cereus JH108 has the function of leucine
      specific endopeptidase. When measured by hydrolysis of synthetic substrate (N
      succinyl-Ala-Ala-Pro-Leu-p-nitroanilide), the enzyme activity exhibited optimal
      activity at pH 9.0, 60 degrees C. The endopeptidase activity was stimulated by
      Ca++, Co++, Mn++, Mg++, and Ni++, and was inhibited by metal chelating agents
      such as EDTA, 1,10-phenanthroline, and EGTA. Addition of serine protease
      inhibitor, PMSF, resulted in the elimination of the activity. The endopeptidase
      activity was fully recovered from the inhibition of EDTA by the addition of 1 mM
      Ca++, and was partially restored by Co++ and Mn++, indicating that the enzyme was
      stabilized and activated by divalent cations and has a serine residue at the
      active site. Addition of Ca++ increased the pH and heat stability of
      endopeptidase activity. These results show that endopeptidase requires calcium
      ions for activity and/or stability. A Lineweaver-Burk plot analysis indicated
      that the Km value of endopeptidase is 0.315 mM and Vmax is 0.222 mmol of N
      succinyl-Ala-Ala-Pro-Leu-p-nitroanilide per min. Bestatin was shown to act as a
      competitive inhibitor to the endopeptidase activity.

PMID- 15995641
TI  - Cytochrome c550 is related to initiation of sporulation in Bacillus subtilis.
AB  - The effect of cytochrome c550 encoded by cccA in Bacillus subtilis during the
      event of sporulation was investigated. The sporulation of cccA-overexpressing
      mutant was significantly accelerated, while disruptant strain showed delayed
      sporulation in spite of the same growth rate. Activity of sporulation stage-0
      specific enzyme, extracellular alpha-amylase of mutant strains was similar to
      that of the control strain, but cccA-overexpressing mutant exhibited higher
      activity of stage-II-specific alkaline phosphatase and stage-III-specific glucose
      dehydrogenase when compared to deletion mutant and control strain. Northern blot
      analysis also revealed that cccA-overexpressing mutant showed high level of spo0A
      transcripts, while the disruptant rarely expressed spo0A. These results suggested
      that although cytochrome c550 is dispensable for growth and sporulation,
      expression of cccA may play an important role for initiation of sporulation
      through regulation of spo0A expression.

PMID- 15995642
TI  - Plasmid profiling and curing of Lactobacillus strains isolated from the
      gastrointestinal tract of chicken.
AB  - In this study, we assessed the susceptibility of 12 Lactobacillus strains, all of
      which had been isolated from the gastrointestinal tracts of chicken, to three
      antibiotics (chloramphenicol, erythromycin and tetracycline) used commonly as
      selective markers in transformation studies of lactic acid bacteria. Among these
      strains, 17%, 58%, and 25% were found to exhibit a high degree of resistance to
      200 microg/ml of tetracycline, erythromycin, and chloramphenicol, respectively.
      Seven of the 12 Lactobacillus strains exhibiting resistance to at least 50
      microg/ml of chloramphenicol or erythromycin, and five strains exhibiting
      resistance to at least 50 microg/ml of tetracycline, were subsequently subjected
      to plasmid curing with chemical curing agents, such as novobiocin, acriflavin,
      SDS, and ethidium bromide. In no cases did the antibiotic resistance of these
      strains prove to be curable, with the exception of the erythromycin resistance
      exhibited by five Lactobacillus strains (L. acidophilus I16 and I26, L. fermentum
      I24 and C17, and L. brevis C10). Analysis of the plasmid profiles of these five
      cured derivatives revealed that all of the derivatives, except for L. acidophilus
      I16, possessed profiles similar to those of wild-type strains. The curing of L.
      acidophilus I16 was accompanied by the loss of 4.4 kb, 6.1 kb, and 11.5 kb
      plasmids.

PMID- 15995643
TI  - Evaluation of negative results of BacT/Alert 3D automated blood culture system.
AB  - Although automated continuous-monitoring blood culture systems are both rapid and
      sensitive, false-positive and false-negative results still occur. The objective
      of this study, then, was to evaluate negative results occurring with BacT/Alert
      3D blood culture systems. A total of 1032 samples were cultured with the
      BacT/Alert 3D automated blood culture system, using both aerobic (FA) and
      anaerobic (FN) [corrected] media, and 128 of these samples yielded positive
      results. A total of 904 negative blood samples were then subcultured in 5% sheep
      blood agar, eosin methylene blue, chocolate agar, and sabouraud-dextrose agar.
      Organisms growing on these subcultures were subsequently identified using both
      Vitek32 (bioMerieux, Durham, NC) and conventional methods. Twenty four (2.6%) of
      the 904 subcultures grew on the subculture media. The majority (83.3%) of these
      were determined to be gram-positive microorganisms. Fourteen (58.3%) were
      coagulase-negative staphylococci, two (8.3%) were Bacillus spp., one (4.2%) was
      Staphylococcus aureus, and one (4.2%) was identified as Enterococcus faecium.
      Streptococcus pneumoniae and Neisseria spp. were isolated together in two (8.3%)
      vials. Gram-negative microorganisms comprised 12.5% of the subcultures, of which
      two (8.3%) were found to be Pseudomonas aeruginosa, and one (4.2%) was
      Pseudomonas fluorescens. The other isolate (4.2%) was identified as Candida
      albicans. We conclude that the subculture of negative results is valuable in the
      BacT/Alert 3D system, especially in situations in which only one set of blood
      cultures is taken.

PMID- 15995644
TI  - Prevalence of putative periodontopathogens in subgingival dental plaques from
      gingivitis lesions in Korean orthodontic patients.
AB  - The objective of this study was to detect and compare the presence of
      periodontopathogens in the subgingival plaques of gingivitis lesions in adults
      who wore fixed orthodontic appliances, as opposed to adults who did not wear any
      orthodontic appliances. Thirty-six individuals participated in this study.
      Nineteen of these subjects did not wear any orthodontic appliances, and these
      subjects comprised the control group. The other 17 individuals had been wearing
      fixed orthodontic appliances for at least 3 months each. After a periodontal
      examination, we collected subgingival plaque samples from the gingivitis lesions
      of each patient. Using PCR based on 16S rDNA, we detected the presence of 6
      putative periodontopathogenic species, Treponema denticola, Porphyromonas
      gingivalis, Tannerella forsythia (formerly Bacteroides forsythus), Prevotella
      nigrescens, Prevotella intermedia, and Actinobacillus actinomycetemcomitans. With
      regard to the presence of individual periodontopathogens, we found that T.
      forsythia, T. denticola, and P. nigrescens were significantly more common in the
      samples obtained from the orthodontic patients than in the samples obtained from
      the non-orthodontic patient controls. Our results indicate that the local changes
      associated with the wearing of fixed orthodontic appliances may affect the
      prevalence of periodontopathogens in subgingival dental plaques.

PMID- 15995645
TI  - Use of Clostridium septicum alpha toxins for isolation of various
      glycosylphosphatidylinositol-deficient cells.
AB  - In eukaryotic cells, various proteins are anchored to the plasma membrane through
      glycosylphosphatidylinositol (GPI). To study the biosynthetic pathways and
      modifications of GPI, various mutant cells have been isolated from the cells of
      Chinese hamster ovaries (CHO) supplemented with several exogenous genes involved
      in GPI biosynthesis using aerolysin, a toxin secreted from gram-negative
      bacterium Aeromonas hydrophila. Alpha toxin from Gram-positive bacterium
      Clostridium septicum is homologous to large lobes (LL) of aerolysin, binds GPI
      anchored proteins and possesses a cell-destroying mechanism similar to aerolysin.
      Here, to determine whether alpha toxins can be used as an isolation tool of GPI
      mutants, like aerolysin, CHO cells stably transfected with several exogenous
      genes involved in GPI biosynthesis were chemically mutagenized and cultured in a
      medium containing alpha toxins. We isolated six mutants highly resistant to alpha
      toxins and deficient in GPI biosynthesis. By genetic complementation, we
      determined that one mutant cell was defective of the second subunit of dolichol
      phosphate mannose synthase (DPM2) and other five cells were of a putative
      catalytic subunit of inositol acyltransferase (PIG-W). Therefore, C. septicum
      alpha toxins are a useful screening probe for the isolation of various GPI-mutant
      cells.

PMID- 15995646
TI  - Isolation, characterization, and investigation of surface and hemolytic
      activities of a lipopeptide biosurfactant produced by Bacillus subtilis ATCC
      6633.
AB  - Bacillus subtilis ATCC 6633 was grown in BHIB medium supplemented with Mn2+ for
      96 h at 37 degrees C in a shaker incubator. After removing the microbial biomass,
      a lipopeptide biosurfactant was extracted from the supernatant. Its structure was
      established by chemical and spectroscopy methods. The structure was confirmed by
      physical properties, such as Hydrophile-Lipophile Balance (HLB), surface activity
      and erythrocyte hemolytic capacity. The critical micelle concentration (cmc) and
      erythrocyte hemolytic capacity of the biosurfactant were compared to those of
      surfactants such as SDS, BC (benzalkonium chloride), TTAB
      (tetradecyltrimethylammonium bromide) and HTAB (hexadecyltrimethylammonium
      bromide). The maximum hemolytic effect for all surfactants mentioned was observed
      at concentrations above cmc. The maximum hemolytic effect of synthetic
      surfactants was more than that of the biosurfactant produced by B. subtilis ATCC
      6633. Therefore, biosurfactant would be considered a suitable surface-active
      agent due to low toxicity to the membrane.

PMID- 15995647
TI  - Alternative production of avermectin components in Streptomyces avermitilis by
      gene replacement.
AB  - The avermectins are composed of eight compounds, which exhibit structural
      differences at three positions. A family of four closely-related major
      components, A1a, A2a, B1a and B2a, has been identified. Of these components, B1a
      exhibits the most potent antihelminthic activity. The coexistence of the "1"
      components and "2" components has been accounted for by the defective dehydratase
      of aveAI module 2, which appears to be responsible for C22-23 dehydration.
      Therefore, we have attempted to replace the dehydratase of aveAI module 2 with
      the functional dehydratase from the erythromycin eryAII module 4, via homologous
      recombination. Erythromycin polyketide synthetase should contain the sole
      dehydratase domain, thus generating a saturated chain at the C6-7 of
      erythromycin. We constructed replacement plasmids with PCR products, by using
      primers which had been derived from the sequences of avermectin aveAI and the
      erythromycin eryAII biosynthetic gene cluster. If the original dehydratase of
      Streptomyces avermitilis were exchanged with the corresponding erythromycin gene
      located on the replacement plasmid, it would be expected to result in the
      formation of precursors which contain alkene at C22-23, formed by the dehydratase
      of erythromycin module 4, and further processed by avermectin polyketide
      synthase. Consequently, the resulting recombinant strain JW3105, which harbors
      the dehydratase gene derived from erythromycin, was shown to produce only C22,23
      unsaturated avermectin compounds. Our research indicates that the desired
      compound may be produced via polyketide gene replacement.

PMID- 15995648
TI  - Molecular characterization of extracellular medium-chain-length poly(3
      hydroxyalkanoate) depolymerase genes from Pseudomonas alcaligenes strains.
AB  - A bacterial strain M4-7 capable of degrading various polyesters, such as
      poly(epsilon-caprolactone), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3
      hydroxyoctanoate), and poly(3-hydroxy-5-phenylvalerate), was isolated from a
      marine environment and identified as Pseudomonas alcaligenes. The relative
      molecular mass of a purified extracellular medium-chain-length poly(3
      hydroxyalkanoate) (MCL-PHA) depolymerase (PhaZ(PalM4-7)) from P. alcaligenes M4-7
      was 28.0 kDa, as determined by SDS-PAGE. The PhaZ(PalM4-7) was most active in 50
      mM glycine-NaOH buffer (pH 9.0) at 35 degrees C. It was insensitive to
      dithiothreitol, sodium azide, and iodoacetamide, but susceptible to p
      hydroxymercuribenzoic acid, N-bromosuccinimide, acetic anhydride, EDTA,
      diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, Tween 80, and Triton
      X-100. In this study, the genes encoding MCL-PHA depolymerase were cloned,
      sequenced, and characterized from a soil bacterium, P. alcaligenes LB19 (Kim et
      al., 2002, Biomacromolecules 3, 291-296) as well as P. alcaligenes M4-7. The
      structural gene (phaZ(PalLB19)) of MCL-PHA depolymerase of P. alcaligenes LB19
      consisted of an 837 bp open reading frame (ORF) encoding a protein of 278 amino
      acids with a deduced M((r)) of 30,188 Da. However, the MCL-PHA depolymerase gene
      (phaZ(PalM4-7)) of P. alcaligenes M4-7 was composed of an 834 bp ORF encoding a
      protein of 277 amino acids with a deduced Mr of 30,323 Da. Amino acid sequence
      analyses showed that, in the two different polypeptides, a substrate-binding
      domain and a catalytic domain are located in the N-terminus and in the C
      terminus, respectively. The PhaZ(PalLB19) and the PhaZ(PalM4-7) commonly share
      the lipase box, GISSG, in their catalytic domains, and utilize 111Asn and 110Ser
      residues, respectively, as oxyanions that play an important role in transition
      state stabilization of hydrolytic reactions.

PMID- 15995649
TI  - Comparative evaluation of three purification methods for the nucleocapsid protein
      of Newcastle disease virus from Escherichia coli homogenates.
AB  - In the present study, the performances of conventional purification methods,
      packed bed adsorption (PBA), and expanded bed adsorption (EBA) for the
      purification of the nucleocapsid protein (NP) of Newcastle disease virus (NDV)
      from Escherichia coli homogenates were evaluated. The conventional methods for
      the recovery of NP proteins involved multiple steps, such as centrifugation,
      precipitation, dialysis, and sucrose gradient ultracentrifugation. For the PBA,
      clarified feedstock was used for column loading, while in EBA, unclarified
      feedstock was used. Streamline chelating immobilized with Ni2+ ion was used as an
      affinity ligand for both PBA and EBA. The final protein yield obtained in
      conventional and PBA methods was 1.26% and 5.56%, respectively. It was
      demonstrated that EBA achieved the highest final protein yield of 9.6% with a
      purification factor of 7. Additionally, the total processing time of the EBA
      process has been shortened by 8 times compared to that of the conventional
      method.

PMID- 15995650
TI  - Laccase production using Pleurotus ostreatus 1804 immobilized on PUF cubes in
      batch and packed bed reactors: influence of culture conditions.
AB  - The feasibility of laccase production by immobilization of Pleurotus ostreatus
      1804 on polyurethane foam (PUF) cubes with respect to media composition was
      studied in both batch and reactor systems. Enhanced laccase yield was evidenced
      due to immobilization. A relatively high maximum laccase activity of 312.6 U was
      observed with immobilized mycelia in shake flasks compared to the maximum laccase
      activity of free mycelia (272.2 U). It is evident from this study that the
      culture conditions studied, i.e. biomass level, pH, substrate concentration,
      yeast extract concentration, Cu2+ concentration, and alcohol nature, showed
      significant influence on the laccase yield. Gel electrophoretic analysis showed
      the molecular weight of the laccase produced by immobilized P. ostreatus to be 66
      kDa. The laccase yield was significantly higher and more rapid in the packed bed
      reactor than in the shake flask experiments. A maximum laccase yield of 392.9 U
      was observed within 144 h of the fermentation period with complete glucose
      depletion.

PMID- 15995651
TI  - A putative early response of antifungal Bacillus lentimorbus WJ5 against the
      plant pathogenic fungus, Colletotrichum gloeosporioides, analyzed by a DNA
      microarray.
AB  - The global RNA transcription profiles of Bacillus lentimorbus WJ5 under an in
      vitro co-culture with Colletotrichum gloeosporioides were analyzed in order to
      study the antagonistic bacteria-fungi interactions. Using a filter membrane
      system, B. lentimorbus WJ5 was exposed to the spores of C. gloeosporioides at the
      late exponential stage. The transcription profiles of the B. lentimorbus WJ5,
      both with and without a challenge from C. gloeosporioides, were analyzed using
      custom DNA chips containing 2,000 genome fragments. A total of 337 genes were
      expressed, with 87 and 47 up- and down-regulated, respectively. Of these, 12
      genes, which were involved in central carbon metabolisms, and 7 from minor
      catabolism were relatively highly up-regulated (> 10 fold) and down-regulated (<
      0.2 fold), respectively. Nine genes, which were thought to be related to the
      antifungal activity, were also up-regulated, but their levels were not so high
      (2.0 - 9.7 folds). From the results, during the early stage of the co-culture of
      B. lentimorbus WJ5 and C. gloeosporioides, nutrient competition seemed to occur;
      therefore, the genes from central carbon metabolisms could be up-regulated, while
      those from minor catabolism could be down-regulated.

PMID- 15995652
TI  - Molecular detection of alpha-glucosidase inhibitor-producing actinomycetes.
AB  - In this study, we demonstrate the use of a PCR-based method for the detection of
      the specific genes involved in natural-product biosynthesis. This method was
      applied, using specifically designed PCR primers, to the amplification of a gene
      segment encoding for sedo-heptulose 7-phosphate cyclase, which appears to be
      involved in the biosynthetic pathways of C7N aminoacyclitol or its keto analogue
      containing metabolites, in a variety of actinomycetes species. The sequences of
      DNA fragments (about 540 bp) obtained from three out of 39 actinomycete strains
      exhibited a high degree of homology with the sedo-heptulose 7-phosphate cyclase
      gene, which has been implicated in acarbose biosynthesis. The selective
      cultivation conditions of this experiment induced the expression of these loci,
      indicating that the range of C7 aminoacyclitol or its keto analogue-group natural
      products might be far greater than was previously imagined. Considering that a
      total of approximately 20 C7 aminoacyclitol metabolites, or its keto analogue
      containing metabolites, have been described to date, it appears likely that some
      of the unknown loci described herein might constitute new classes of C7
      aminoacyclitol, or of its keto analogue-containing metabolites. As these
      metabolites, some of which contain valienamine, are among the most potent
      antidiabetic agents thus far discovered, the molecular detection of specific
      metabolite-producing actinomycetes may prove a crucial step in current attempts
      to expand the scope and diversity of natural-product discovery.

PMID- 15995653
TI  - New approaches to quantifying the spread of infection.
AB  - Recent major disease outbreaks, such as severe acute respiratory syndrome and
      foot-and-mouth disease in the UK, coupled with fears of emergence of human-to
      human transmissible variants of avian influenza, have highlighted the importance
      of accurate quantification of disease threat when relatively few cases have
      occurred. Traditional approaches to mathematical modelling of infectious diseases
      deal most effectively with large outbreaks in large populations. The desire to
      elucidate the highly variable dynamics of disease spread amongst small numbers of
      individuals has fuelled the development of models that depend more directly on
      surveillance and contact-tracing data. This signals a move towards a closer
      interplay between epidemiological modelling, surveillance and disease-management
      strategies.

PMID- 15995655
TI  - Programmed ageing: the theory of maximal metabolic scope. How does the biological
      clock tick?

PMID- 15995656
TI  - Increasing longevity by tuning up metabolism. To maximize human health and
      lifespan, scientists must abandon outdated models of micronutrients.

PMID- 15995657
TI  - Anti-ageing strategies: prevention or therapy? Showing ageing from within.

PMID- 15995658
TI  - Youthful prospects for human stem-cell therapy. In another few decades, revised
      attitudes toward stem cells could lead to disease prevention and life extension.

PMID- 15995659
TI  - Stem cells and ageing. The potential of stem cells to overcome age-related
      deteriorations of the body in regenerative medicine.

PMID- 15995660
TI  - Of mice and men. When it comes to studying ageing and the means to slow it down,
      mice are not just small humans.

PMID- 15995661
TI  - Time of our lives. What controls the length of life?

PMID- 15995662
TI  - Ageing, science and the cosmetics industry. The micro-inflammatory model serves
      as a basis for developing effective anti-ageing products for the skin.

PMID- 15995663
TI  - Resistance to debate on how to postpone ageing is delaying progress and costing
      lives. Open discussions in the biogerontology community would attract public
      interest and influence funding policy.

PMID- 15995664
TI  - Cultural aspects of time and ageing. Time is not the same in every culture and
      every circumstance; our views of aging also differ.

PMID- 15995665
TI  - Medicine, ageing and human longevity. The economics and ethics of anti-ageing
      interventions.

PMID- 15995666
TI  - To everything there is a season? Time, eternity and the promise of extending
      human life.

PMID- 15995667
TI  - The choosy reaper. From the myth of eternal youth to the reality of unequal
      death.

PMID- 15995668
TI  - Death as an unnatural process. Why is it wrong to seek a cure for aging?

PMID- 15995669
TI  - The rise of a culture of life. The biological sciences are encouraging the move
      away from the ideals of the Enlightenment towards an idea of individual
      perfectibility and enhancement.

PMID- 15995670
TI  - Ageing research in the media. How the demands of newspaper and magazine
      publishing influence what people read about aging.

PMID- 15995671
TI  - The daily rhythms of genes, cells and organs. Biological clocks and circadian
      timing in cells.

PMID- 15995672
TI  - Scientists: ignored gold.

PMID- 15995673
TI  - The parable of the mandarin.

PMID- 15995674
TI  - Molecular farming for new drugs and vaccines. Current perspectives on the
      production of pharmaceuticals in transgenic plants.

PMID- 15995675
TI  - Future trends and challenges in pathogenomics. A Foresight study.

PMID- 15995676
TI  - What's in store for animal research in the EU? Researchers should have little to
      fear from the EU's new animal-welfare directive, but the menace is in the
      minutiae.

PMID- 15995677
TI  - Skullduggery. The discovery of an unusual human skeleton has broad implications.

PMID- 15995678
TI  - Disease mongering and drug marketing. Does the pharmaceutical industry
      manufacture diseases as well as drugs?

PMID- 15995679
TI  - Light and oxygenic photosynthesis: energy dissipation as a protection mechanism
      against photo-oxidation.
AB  - Efficient photosynthesis is of fundamental importance for plant survival and
      fitness. However, in oxygenic photosynthesis, the complex apparatus responsible
      for the conversion of light into chemical energy is susceptible to photodamage.
      Oxygenic photosynthetic organisms have therefore evolved several protective
      mechanisms to deal with light energy. Rapidly inducible non-photochemical
      quenching (NPQ) is a short-term response by which plants and eukaryotic algae
      dissipate excitation energy as heat. This review focuses on recent advances in
      the elucidation of the molecular mechanisms underlying this protective quenching
      pathway in higher plants.

PMID- 15995687
TI  - USDA clarifies practice for certain adjudicatory proceedings.

PMID- 15995688
TI  - Overnight postoperative monitoring: not in this case.

PMID- 15995689
TI  - Overnight postoperative monitoring: yes (and no).

PMID- 15995690
TI  - Overnight postoperative monitoring: necessity or not?

PMID- 15995691
TI  - Overnight postoperative monitoring: proposal justified.

PMID- 15995692
TI  - Red specks on honey bees (Apis mellifera).

PMID- 15995694
TI  - Laboratory culture and maintenance of the horseshoe crab (Limulus polyphemus).
AB  - Often referred to as a living fossil, the American horseshoe crab, Limulus
      polyphemus, is one of the most-studied invertebrate animals in the world. It has
      served as a model in Nobel Prize-winning eye research, and researchers use a
      component of its blood to detect bacterial contamination in medical devices and
      drugs. The authors review the conditions necessary for housing these animals in
      the laboratory.

PMID- 15995695
TI  - Earthquakes and building design: a primer for the laboratory animal professional.
AB  - Earthquakes can occur in most regions of the United States, so it might be
      necessary to reinforce vulnerable animal facilities to better protect research
      animals during these unpredictable events. A risk analysis should include an
      evaluation of the seismic hazard risk at the proposed building site balanced
      against the estimated consequences of losses. Risk analysis can help in better
      justifying and recommending to building owners the costs of incorporating
      additional seismic reinforcements. The planning team needs to specify the level
      of post-earthquake building function that is desired in the facility, and then
      design the facility to it.

PMID- 15995696
TI  - The genetics of addictions: uncovering the genes.
AB  - The addictions are common chronic psychiatric diseases that today are prevented
      and treated using relatively untargeted and only partially effective methods. The
      addictions are moderately to highly heritable, which is paradoxical because these
      disorders require use; a choice that is itself modulated by both genes and
      environment. The addictions are interrelated and related to other psychiatric
      diseases by common neurobiological pathways, including those that modulate
      reward, behavioural control and the anxiety or stress response. Our future
      understanding of addictions will be enhanced by the identification of genes that
      have a role in altered substance-specific vulnerabilities such as variation in
      drug metabolism or drug receptors and a role in shared vulnerabilities such as
      variation in reward or stress resiliency.

PMID- 15995697
TI  - Synthetic biology.
AB  - Synthetic biologists come in two broad classes. One uses unnatural molecules to
      reproduce emergent behaviours from natural biology, with the goal of creating
      artificial life. The other seeks interchangeable parts from natural biology to
      assemble into systems that function unnaturally. Either way, a synthetic goal
      forces scientists to cross uncharted ground to encounter and solve problems that
      are not easily encountered through analysis. This drives the emergence of new
      paradigms in ways that analysis cannot easily do. Synthetic biology has generated
      diagnostic tools that improve the care of patients with infectious diseases, as
      well as devices that oscillate, creep and play tic-tac-toe.

PMID- 15995698
TI  - Insertional mutagenesis in mice: new perspectives and tools.
AB  - Insertional mutagenesis has been at the core of functional genomics in many
      species. In the mouse, improved vectors and methodologies allow easier genome
      wide and phenotype-driven insertional mutagenesis screens. The ability to
      generate homozygous diploid mutations in mouse embryonic stem cells allows
      prescreening for specific null phenotypes prior to in vivo analysis. In addition,
      the discovery of active transposable elements in vertebrates, and their
      development as genetic tools, has led to in vivo forward insertional mutagenesis
      screens in the mouse. These new technologies will greatly contribute to the speed
      and ease with which we achieve complete functional annotation of the mouse
      genome.

PMID- 15995699
TI  - The DNA damage pathway regulates innate immune system ligands of the NKG2D
      receptor.
AB  - Some stimulatory receptors of the innate immune system, such as the NKG2D
      receptor (also called KLRK1) expressed by natural killer cells and activated
      CD8(+)T cells, recognize self-molecules that are upregulated in diseased cells by
      poorly understood mechanisms. Here we show that mouse and human NKG2D ligands are
      upregulated in non-tumour cell lines by genotoxic stress and stalled DNA
      replication, conditions known to activate a major DNA damage checkpoint pathway
      initiated by ATM (ataxia telangiectasia, mutated) or ATR (ATM- and Rad3-related)
      protein kinases. Ligand upregulation was prevented by pharmacological or genetic
      inhibition of ATR, ATM or Chk1 (a downstream transducer kinase in the pathway).
      Furthermore, constitutive ligand expression by a tumour cell line was inhibited
      by targeting short interfering RNA to ATM, suggesting that ligand expression in
      established tumour cells, which often harbour genomic irregularities, may be due
      to chronic activation of the DNA damage response pathway. Thus, the DNA damage
      response, previously shown to arrest the cell cycle and enhance DNA repair
      functions, or to trigger apoptosis, may also participate in alerting the immune
      system to the presence of potentially dangerous cells.

PMID- 15995700
TI  - Continuous flash suppression reduces negative afterimages.
AB  - Illusions that produce perceptual suppression despite constant retinal input are
      used to manipulate visual consciousness. Here we report on a powerful variant of
      existing techniques, continuous flash suppression. Distinct images flashed
      successively at approximately 10 Hz into one eye reliably suppress an image
      presented to the other eye. The duration of perceptual suppression is at least
      ten times greater than that produced by binocular rivalry. Using this tool we
      show that the strength of the negative afterimage of an adaptor was reduced by
      half when it was perceptually suppressed by input from the other eye. The more
      completely the adaptor was suppressed, the more strongly the afterimage intensity
      was reduced. Paradoxically, trial-to-trial visibility of the adaptor did not
      correlate with the degree of reduction. Our results imply that formation of
      afterimages involves neuronal structures that access input from both eyes but
      that do not correspond directly to the neuronal correlates of perceptual
      awareness.

PMID- 15995701
TI  - Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy.
AB  - Glial cells actively participate in synaptic transmission. They clear molecules
      from the synaptic cleft, receive signals from neurons and, in turn, release
      molecules that can modulate signaling between neuronal elements. Whether glial
      derived transmitters can contribute to enduring changes in postsynaptic efficacy,
      however, remains to be established. In rat hypothalamic paraventricular nucleus,
      we demonstrate an increase in the amplitude of miniature excitatory postsynaptic
      currents in response to norepinephrine that requires the release of ATP from
      glial cells. The increase in quantal efficacy, which likely results from an
      insertion of AMPA receptors, is secondary to the activation of P2X(7) receptors,
      an increase in postsynaptic calcium and the activation of phosphatidylinositol 3
      kinase. The gliotransmitter ATP, therefore, contributes directly to the
      regulation of postsynaptic efficacy at glutamatergic synapses in the CNS.

PMID- 15995702
TI  - Synchronized retinal oscillations encode essential information for escape
      behavior in frogs.
AB  - Synchronized oscillatory activity is generated among visual neurons in a manner
      that depends on certain key features of visual stimulation. Although this
      activity may be important for perceptual integration, its functional significance
      has yet to be explained. Here we find a very strong correlation between
      synchronized oscillatory activity in a class of frog retinal ganglion cells
      (dimming detectors) and a well-known escape response, as shown by behavioral
      tests and multi-electrode recordings from isolated retinas. Escape behavior
      elicited by an expanding dark spot was suppressed and potentiated by intraocular
      injection of GABA(A) receptor and GABA(C) receptor antagonists, respectively.
      Changes in escape behavior correlated with antagonist-evoked changes in
      synchronized oscillatory activity but not with changes in the discharge rate of
      dimming detectors. These antagonists did not affect the expanding dark spot
      induced responses in retinal ganglion cells other than dimming detectors. Thus,
      synchronized oscillations in the retina are likely to encode escape-related
      information in frogs.

PMID- 15995703
TI  - A deafness mutation isolates a second role for the tectorial membrane in hearing.
AB  - Alpha-tectorin (encoded by Tecta) is a component of the tectorial membrane, an
      extracellular matrix of the cochlea. In humans, the Y1870C missense mutation in
      TECTA causes a 50- to 80-dB hearing loss. In transgenic mice with the Y1870C
      mutation in Tecta, the tectorial membrane's matrix structure is disrupted, and
      its adhesion zone is reduced in thickness. These abnormalities do not seriously
      influence the tectorial membrane's known role in ensuring that cochlear feedback
      is optimal, because the sensitivity and frequency tuning of the mechanical
      responses of the cochlea are little changed. However, neural thresholds are
      elevated, neural tuning is broadened, and a sharp decrease in sensitivity is seen
      at the tip of the neural tuning curve. Thus, using Tecta(Y1870C/+) mice, we have
      genetically isolated a second major role for the tectorial membrane in hearing:
      it enables the motion of the basilar membrane to optimally drive the inner hair
      cells at their best frequency.

PMID- 15995704
TI  - Sox21 promotes the progression of vertebrate neurogenesis.
AB  - The generation of neurons constitutes the foundation of nervous system
      development, yet the mechanisms underlying neurogenesis are not well established.
      The HMG-box transcription factors Sox1, Sox2 and Sox3 (Sox1-3) have previously
      been shown to suppress neurogenesis by maintaining neural cells in an
      undifferentiated state. Here we report that another HMG-box protein, Sox21, has
      the opposite activity and promotes neuronal differentiation. Using genetic
      studies in the chick embryo, we found that Sox21 mediates this function by
      counteracting the activity of Sox1-3. Accordingly, the balance of Sox21 and Sox1
      3 activities determines whether neural cells remain as progenitors or commit to
      differentiation. Proneural basic helix-loop-helix proteins are essential for the
      establishment of neuronal fates. We now show that proneural proteins promote
      neurogenesis by upregulating Sox21 expression. These data establish a key role
      for Sox21 in the progression of neuronal differentiation and indicate that an
      important role of proneural proteins is their capacity to upregulate the
      expression of Sox21.

PMID- 15995705
TI  - Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis
      in mice and humans.
AB  - Fibrogenesis or scarring of the liver is a common consequence of all chronic
      liver diseases. Here we refine a quantitative trait locus that confers
      susceptibility to hepatic fibrosis by in silico mapping and show, using congenic
      mice and transgenesis with recombined artificial chromosomes, that the gene Hc
      (encoding complement factor C5) underlies this locus. Small molecule inhibitors
      of the C5a receptor had antifibrotic effects in vivo, and common haplotype
      tagging polymorphisms of the human gene C5 were associated with advanced fibrosis
      in chronic hepatitis C virus infection. Thus, the mouse quantitative trait gene
      led to the identification of an unknown gene underlying human susceptibility to
      liver fibrosis, supporting the idea that C5 has a causal role in fibrogenesis
      across species.

PMID- 15995706
TI  - Inversion-induced disruption of the Hoxd cluster leads to the partition of
      regulatory landscapes.
AB  - The developmental regulation of vertebrate Hox gene transcription relies on the
      interplay between local and long-range controls. To study this complex genomic
      organization, we designed a strategy combining meiotic and targeted
      recombinations to induce large chromosomal rearrangements in vivo without
      manipulating embryonic stem cells. With this simple approach (called STRING), we
      engineered a large 7-cM inversion, which split the Hoxd cluster into two
      independent pieces. Expression analyses showed a partition of global enhancers,
      allowing for their precise topographic allocation on either side of the cluster.
      Such a functional organization probably contributed to keeping these genes
      clustered in the course of vertebrate evolution. This approach can be used to
      study the relationship between genome architecture and gene expression, such as
      the effects of genome rearrangements in human diseases or during evolution.

PMID- 15995709
TI  - Secondary myelodysplasia of donor cell origin following nonmyeloablative sibling
      allogeneic stem cell transplantation.

PMID- 15995708
TI  - Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte
      chemotaxis.
AB  - Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its
      ligand CCL2 results in activation of the cascade consisting of
      phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and
      lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat
      homology protein, FROUNT, directly bound activated CCR2 and formed clusters at
      the cell front during chemotaxis. Overexpression of FROUNT amplified the
      chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent
      chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense
      strategy substantially diminished signaling via CCR2. In a mouse peritonitis
      model, suppression of endogenous FROUNT markedly prevented macrophage
      infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium
      protrusion cascade and could be a therapeutic target in chronic inflammatory
      immune diseases associated with macrophage infiltration.

PMID- 15995707
TI  - Selected Toll-like receptor agonist combinations synergistically trigger a T
      helper type 1-polarizing program in dendritic cells.
AB  - Toll-like receptors (TLRs) sense microbial products and initiate adaptive immune
      responses by activating dendritic cells (DCs). As pathogens may contain several
      TLR agonists, we sought to determine whether different TLRs cooperate in DC
      activation. In human and mouse DCs, TLR3 and TLR4 potently acted in synergy with
      TLR7, TLR8 and TLR9 in the induction of a selected set of genes. Synergic TLR
      stimulation increased production of interleukins 12 and 23 and increased the
      Delta-4/Jagged-1 ratio, leading to DCs with enhanced and sustained T helper type
      1-polarizing capacity. Global gene transcriptional analysis showed that TLR
      synergy 'boosted' only approximately 1% of the transcripts induced by single TLR
      agonists. These results identify a 'combinatorial code' by which DCs discriminate
      pathogens and suggest new strategies for promoting T helper type 1 responses.

PMID- 15995710
TI  - Varicella zoster virus (VZV)-related progressive outer retinal necrosis (PORN)
      after allogeneic stem cell transplantation.

PMID- 15995711
TI  - Complete substitution of cyclophosphamide by fludarabine and ATG in a busulfan
      based preparative regimen for children and adolescents with beta-thalassemia.
AB  - Children and adolescents with homozygous beta-thalassemia can be cured by
      transplantation of normal stem cells after eradication of the thalassemic
      hematopoietic system. In an attempt to achieve durable engraftment and to
      minimize regimen-related toxicity (RRT), we have initiated a fludarabine-based
      pilot protocol not containing cyclophosphamide. Between 1999 and 2004, five
      children with beta-thalassemia major were enrolled. Median age at transplantation
      was 11.5 years (range 4-14 years). Three patients received conditioning with
      fludarabine (30 mg/m2/day x 6), oral busulfan (3.5 mg/kg/day x 4), and ATG rabbit
      Fresenius (10 mg/kg/day x 4). Two children received intravenous busulfan instead
      of oral busulfan at a dose of 2 x 1.4 mg/kg/day x 4 days. All children were
      transplanted with a fresh bone marrow graft from an HLA-identical sibling. Mean
      cell doses given were 3.7 x 10(8) nucleated cells/kg BW (range 2.4-6.2 x
      10(8)/kg). Overall, 5/5 patients achieved donor engraftment and are alive and
      well. No GVHD exceeding grade I was observed, and 2/5 children maintained donor
      chimerism at 100%. One patient maintains mixed hematopoietic donor chimerism
      being between 94 and 97% nearly 5 years after transplant.

PMID- 15995712
TI  - Autologous transplantation followed closely by reduced-intensity allogeneic
      transplantation as consolidative immunotherapy in advanced lymphoma patients: a
      feasibility study.
AB  - We report outcomes in advanced lymphoma patients (n = 32) who enrolled in a trial
      of prospectively planned combined autologous/reduced-intensity transplantation
      (RIT) (n = 25) or who received RIT shortly after prior autografting because of
      high relapse risk or progressive disease (n = 7). Nine patients on the
      autologous/RIT transplant protocol did not proceed to planned RIT because of
      patient choice (n = 4), disease progression (n = 3), toxicity (n = 1), or no
      adequate donor (n = 1). Among the 23 other patients, RIT was started a median of
      59 days (range 31-123) after autologous transplant. Fifteen patients had related
      donors, five patients had unrelated donors, and three patients had cord blood
      donors. Among all patients completing RIT, the median overall survival time was
      385 days (95% CI 272-792), and the median relapse-free survival time was 157 days
      (95% CI 119-385). At the time of reporting, six patients (26%) remain alive and
      three patients (13%) remain alive without relapse. The 100-day transplant-related
      mortality (TRM) was 9% among all patients and was 0% among matched sibling
      donors. Overall TRM was 43%. Tandem transplant is feasible in advanced lymphoma
      with low early TRM. However, practical challenges associated with the strategy
      were significant and high levels of late TRM due to graft-versus-host disease and
      infections suggest that modifications of the procedure will be needed to improve
      outcomes and patient retention.

PMID- 15995713
TI  - National estimates of the use of hematopoietic stem-cell transplantation in
      children with cancer in the United States.
AB  - National utilization data for hematopoietic stem-cell transplantation (HSCT) for
      childhood cancers in the United States have not been reported. We identified
      cancer encounters for children aged 18 years and younger from 1997 to 2001 in US
      nonfederal, acute care hospitals. We compared patient, hospital, and resource use
      characteristics and in-patient mortality associated with HSCT and non-HSCT
      encounters, estimated the number of HSCT encounters by stem-cell source and
      cancer type, and examined resource use and mortality in each category. We
      identified 461,175 cancer encounters, of which 6380 (1.4%) were HSCT encounters.
      There was wide variation in resource use and mortality by stem-cell source and
      cancer type. Of note, 17% of HSCT encounters were for patients with acute
      lymphoblastic leukemia without remission or sarcoma, conditions for which there
      is little evidence of benefit from HSCT in children. These encounters were
      associated with high in-patient mortality and long lengths of stay. Also, we
      observed an increasing use of cord blood over the study period. Future research
      should examine potentially important sociodemographic differences in patients
      undergoing HSCT compared to those who do not. Additional analyses incorporating
      disease stage and severity are needed.

PMID- 15995714
TI  - Reduced-intensity allogeneic hematopoietic stem cell transplantation for acute
      leukemias: 'what is the best recipe?'.
AB  - Reduced-intensity stem cell transplantation (RIST) has been shown to be a safe
      and useful alternative transplant method for patients including elderly and
      medically unfit patients. RIST conditioning regimens vary widely in the intensity
      of myeloablation, immunoablation, and antileukemia effects, and thus optimal
      regimen for each disease entity is yet to be determined. Most reports on RIST to
      date are small, single-institution experiences or retrospective studies with
      heterogeneous patient populations and primary diseases, complicating any direct
      comparison between studies. In acute myeloid leukemia (AML), moderate-intensity
      regimens may be effective, achieving 30-70% 1-year disease-free survival in
      various series, but minimal-intensity regimens are associated with high relapse
      rates. In acute lymphoblastic leukemia (ALL), not even moderate-intensity
      regimens are effective and most patients with advanced ALL relapse post
      transplant. Thus, the risk/benefit ratios of graft-versus-host disease/graft
      versus-leukemia effect differ among diseases. Larger, prospective, multi-center
      clinical trials are needed to determine the best use of RIST in hematologic
      malignancies.

PMID- 15995715
TI  - Successful HSCT using nonradiotherapy-based conditioning regimens and alternative
      donors in patients with Fanconi anaemia--experience in a single UK centre.
AB  - Seven children with Fanconi anaemia (FA) (five female, two male), who had not
      undergone transformation, received nine haemopoietic stem cell transplantation
      (HSCT) between 2000 and 2004. Conditioning regimen was: fludarabine 25-30
      mg/m2/day for 5 days, antilymphocyte globulin 12.5 mg/kg/day for 3 days and
      cyclophosphamide 5-7.5 mg/kg/day for 4 days. Radiation was not used. One male
      patient who had multiple HSCT and one female who was retransplanted, received
      slightly different conditioning regimens. Four patients received fully matched
      unrelated umbilical cord blood (UCB), two matched unrelated peripheral blood stem
      cell (PBSC) grafts, and three haploidentical T-cell-depleted (TCD) PBSC grafts.
      None of the patients had any significant conditioning-related toxicity or severe
      infections. All engrafted within 2-3 weeks. One patient rejected her first HSCT
      after 10 weeks and had a second successful transplant from the same donor. One
      male patient rejected his TCD haploidentical HSCT from his mother, and
      subsequently had a successful fully matched unrelated UCB transplant. Rejection
      rate was 22%. Acute and chronic graft-versus-host disease (GVHD) was seen in 77
      and 22% patients. In all, 57% patients developed autoimmune complications, all of
      which have resolved. All patients are well with stable or full donor chimerism
      after a median follow-up of 37 months (range 13-54).

PMID- 15995716
TI  - A fatal Clostridium infection in an allogeneic stem cell transplant recipient.

PMID- 15995717
TI  - Comorbidity indices in hematopoietic stem cell transplantation: a new report
      card.
AB  - Comorbid conditions have not been studied systematically for impact upon patient
      outcome in the setting of hematopoietic stem cell transplantation (HSCT).
      Patients formerly excluded from myeloablative transplant due to comorbid
      illnesses now receive reduced-intensity conditioning regimens; hence, the
      incidence of comorbid conditions in HSCT recipients is expected to increase.
      Comorbid grading systems developed without regard for oncology patients have been
      applied in retrospective fashion to HSCT patients. Two commonly used scales
      (Charlson Comorbidity Index and the Adult Comorbidity Inventory-27) fail to
      include critical information: tumor and histologic type/stage, extent of prior
      treatment, donor stem cell source and cell type and preparative regimen. Further,
      data are reported in retrospective rather than prospective fashion. Despite
      limitations, however, such grading systems exhibit ease and utility for
      evaluation and may have predictive value for patient outcome. Modifying such
      approaches to include additional factors and appropriate weighting of components
      may enable an improved comparison of techniques and study results. These scoring
      systems may elucidate predictors of outcome and disease natural history and
      enhance statistical efficiency methods of HSCT. Refined scoring could be used
      effectively to assign patients to differing transplant conditioning regimens,
      that is, myeloablative vs reduced intensity. Prospective validation of such
      grading systems is encouraged.

PMID- 15995718
TI  - Inhibition of phosphodiesterase 11 (PDE11) impacts on sperm quality.

PMID- 15995720
TI  - Let's make NO mistake!

PMID- 15995722
TI  - The development of nociceptive circuits.
AB  - The study of pain development has come into its own. Reaping the rewards of years
      of developmental and molecular biology, it has now become possible to translate
      fundamental knowledge of signalling pathways and synaptic physiology into a
      better understanding of infant pain. Research has cast new light on the
      physiological and pharmacological processes that shape the newborn pain response,
      which will help us to understand early pain behaviour and to design better
      treatments. Furthermore, it has shown how developing pain circuitry depends on
      non-noxious sensory activity in the healthy newborn, and how early injury can
      permanently alter pain processing.

PMID- 15995723
TI  - Role of the immune system in chronic pain.
AB  - During the past two decades, an important focus of pain research has been the
      study of chronic pain mechanisms, particularly the processes that lead to the
      abnormal sensitivity - spontaneous pain and hyperalgesia - that is associated
      with these states. For some time it has been recognized that inflammatory
      mediators released from immune cells can contribute to these persistent pain
      states. However, it has only recently become clear that immune cell products
      might have a crucial role not just in inflammatory pain, but also in neuropathic
      pain caused by damage to peripheral nerves or to the CNS.

PMID- 15995725
TI  - Placebos and painkillers: is mind as real as matter?
AB  - Considerable progress has been made in our understanding of the neurobiological
      mechanisms of the placebo effect, and most of our knowledge originates from the
      field of pain and analgesia. Today, the placebo effect represents a promising
      model that could allow us to shed new light on mind-body interactions. The mental
      events induced by placebo administration can activate mechanisms that are similar
      to those activated by drugs, which indicates a similarity between psychosocial
      and pharmacodynamic effects. These new neurobiological advances are already
      changing our conception of how clinical trials and medical practice must be
      viewed and conducted.

PMID- 15995724
TI  - Pain and emotion interactions in subregions of the cingulate gyrus.
AB  - Acute pain and emotion are processed in two forebrain networks, and the cingulate
      cortex is involved in both. Although Brodmann's cingulate gyrus had two divisions
      and was not based on any functional criteria, functional imaging studies still
      use this model. However, recent cytoarchitectural studies of the cingulate gyrus
      support a four-region model, with subregions, that is based on connections and
      qualitatively unique functions. Although the activity evoked by pain and emotion
      has been widely reported, some view them as emergent products of the brain rather
      than of small aggregates of neurons. Here, we assess pain and emotion in each
      cingulate subregion, and assess whether pain is co-localized with negative
      affect. Amazingly, these activation patterns do not simply overlap.

PMID- 15995726
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Di-isononyl Phthalate (DINP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for di-isononyl
      phthalate (DINP) to cause adverse effects on reproduction and development in
      humans. DINP is one of 7 phthalate chemicals evaluated by the NTP CERHR
      Phthalates Expert Panel. These phthalates were selected for evaluation because of
      high production volume, extent of human exposures, use in children's products,
      and/or published evidence of reproductive or developmental toxicity. DINP is a
      mixture of branched, C-9 phthalate isomers used to add flexibility to a wide
      variety of plastic products such as toys, garden hoses, flooring tiles, tarps,
      and pool liners. The results of this evaluation on DINP are published in a NTP
      CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on
      the Reproductive and Developmental Toxicity of Di-isononyl Phthalate, and 3)
      public comments received on the Expert Panel Report. As stated in the NTP Brief,
      the NTP reached the following conclusions regarding the possible effects of
      exposure to DINP on human development and reproduction. First, although DINP
      could possibly affect human development if exposures are sufficiently high, there
      is minimal concern for DINP causing adverse effects to human reproduction or
      fetal development. There is no direct evidence that exposure of people to DINP
      adversely affects reproduction or development, but studies show that oral
      exposure of pregnant rats to high doses (500 and 1000 mg/kg bodyweight/day) of
      DINP can adversely affect fetal development. Effects on pup growth were noted in
      a 2-generation reproductive toxicity study in rats at doses of 143-285 mg/kg body
      weight/day. Human exposure information for DINP was not available but it was
      assumed that the general US population would be exposed to 3-30 mug/kg body
      weight/day, based upon the range of estimated exposures for DEHP, a more widely
      used phthalate. Second, based on estimates of exposure of children to DINP from
      mouthing toys and other objects, the NTP has minimal concern for developmental
      effects in children. After the expert panel meeting, a US Consumer Products
      Safety Commission panel estimated that the majority of children exposed to DINP
      had a "minimum to non-existent risk of injury" from mouthing toys. Children's
      exposure was estimated at 70-280 mug/kg body weight/day, a level 1000-fold lower
      than exposures resulting in developmental effects in rats. NTP-CERHR monographs
      are transmitted to federal and state agencies, interested parties, and the public
      and are available electronically in PDF format on the CERHR web site
      (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR
      (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32,
      Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995727
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Di-Isodecyl Phthalate (DIDP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for di-isodecyl
      phthalate (DIDP) to cause adverse effects on reproduction and development in
      humans. DIDP is one of 7 phthalate chemicals evaluated by the NTP CERHR
      Phthalates Expert Panel. These phthalates were selected for evaluation because of
      high production volume, extent of human exposures, use in children's products,
      and/or published evidence of reproductive or developmental toxicity. DIDP is a
      mixture of branched, C-10 phthalate isomers used to add flexibility to a wide
      variety of polyvinylchloride (PVC) plastic products such as artificial leather,
      toys, carpet backing, and pool liners. The results of this evaluation on DIDP are
      published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the
      Expert Panel Report on the Reproductive and Developmental Toxicity of Di-Isodecyl
      Phthalate, and 3) public comments received on the Expert Panel Report. As stated
      in the NTP Brief, the NTP reached the following conclusions regarding the
      possible effects of exposure to DIDP on human development and reproduction.
      First, although DIDP could possibly affect human development if exposures are
      sufficiently high, there is minimal concern for developmental effects in fetuses
      and children at current proposed/estimated exposure levels. There is no direct
      evidence that exposure of people to DIDP adversely affects reproduction or
      development, but show that oral exposure of pregnant rats to high doses (200 and
      1000 mg/kg bodyweight/day) of DIDP can adversely affect fetal development. Human
      exposure information for DIDP was not available, but it was assumed that the
      general US population would be exposed to 3-30 mug/kg body weight/day, based upon
      the range of estimated exposures for DEHP, a more widely used phthalate. Second,
      there is negligible concern for reproductive toxicity in exposed adults. Studies
      evaluated showed that, at high exposure levels, there is no evidence of adverse
      reproductive effects in rats. NTP-CERHR monographs are transmitted to federal and
      state agencies, interested parties, and the public and are available
      electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov)
      and in printed text or CD-ROM from the CERHR (National Institute of Environmental
      Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919
      316-4511).

PMID- 15995728
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Di-n-Octyl Phthalate (DnOP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for di-n-octyl
      phthalate (DnOP) to cause adverse effects on reproduction and development in
      humans. DnOP is one of 7 phthalate chemicals evaluated by the NTP CERHR
      Phthalates Expert Panel. These phthalates were selected for evaluation because of
      high production volume, extent of human exposures, use in children's products,
      and/or published evidence of repro- ductive or developmental toxicity. Available
      information indicates that there are no commercial uses of pure DnOP. However,
      DnOP comprises approximately 20% of the commercially important C6-10 phthalate
      mixture, which is used in flooring and carpet tiles, tarps, pool liners, and
      garden hoses. DnOP is approved by the FDA as an indirect food additive and is
      used in seam cements, bottle cap liners, and conveyor belts. The results of this
      evaluation on DnOP are published in an NTP-CERHR monograph which includes: 1) the
      NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental
      Toxicity of DnOP, and 3) public comments received on the Expert Panel Report. As
      stated in the NTP Brief, the NTP reached the following conclusions regarding the
      possible effects of exposure to DnOP on human development and reproduction.
      Limited studies in mice and rats show that high exposures to DnOP may cause
      adverse developmental effects, but no evidence of reproductive effects was
      observed. In a continuous breeding study, no adverse effects were observed in the
      treated parents or their offspring after dosed feed exposure of mice (approx.
      1,800, 3,600, or 7,500 mg/kg body weight/day). Human exposure information for
      DnOP was not available but it was assumed that the general US population would be
      exposed to 3-30 mug/kg body weight/day, based upon the range of estimated
      exposures for DEHP. Based on this assumption, NTP concluded that there is
      negligible concern for effects on adult reproductive systems. Two developmental
      studies were evaluated by the panel. In the first study, pregnant rats were
      treated with 5,000 and 10,000 mg/kg body weight/day DnOP by intraperitoneal
      injection on gestational days 5, 10, and 15. Increased fetal malformations and
      reduced body weights were observed at both doses. In the second study, pregnant
      mice were treated by gavage with approx. 10,000 mg/kg bodyweight/day on
      gestational days 6-13 and were allowed to deliver the pups. The treated group had
      reduced litter size, but birth weights and pup survival to postnatal day 3 were
      not affected. These studies did not determine an exposure level at which no
      adverse effects occur. The NTP concluded that there is insufficient information
      on developmental toxicity to reach a conclusion regarding the potential for DnOP
      to adversely affect human development. NTP-CERHR monographs are transmitted to
      federal and state agencies, interested parties, and the public and are available
      in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and
      in printed text or CD-ROM from the CERHR (National Institute of Environmental
      Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919
      316-4511).

PMID- 15995729
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Di-n-Hexyl Phthalate (DnHP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for di-n-hexyl
      phthalate (DnHP) to cause adverse effects on reproduction and development in
      humans. DnHP is one of 7 phthalate chemicals evaluated by the NTP CERHR
      Phthalates Expert Panel. These phthalates were selected for evaluation because of
      high production volume, extent of human exposures, use in children's products,
      and/or published evidence of reproductive or developmental toxicity. Available
      information indicates that DnHP is manufactured in relatively small amounts but
      occurs in a variety of commercial products including dip-molded products such as
      tool handles or dishwasher baskets, flooring, vinyl gloves, flea collars, and
      conveyer belts used in food processing. The results of this evaluation on DnHP
      are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the
      Expert Panel Report on the Reproductive and Developmental Toxicity of DnHP, and
      3) public comments received on the Expert Panel Report. As stated in the NTP
      Brief, the NTP reached the following conclusions regarding the possible effects
      of exposure to DnHP on human development and reproduction. The scientific
      evidence was insufficient to reach a conclusion regarding the potential for DnHP
      to adversely affect human development or reproduction. There was very limited
      information on developmental and reproductive toxicity available to the panel.
      The panel evaluated only a single developmental toxicity study using a high dose
      (9,900 mg/kg body weight/day on gestational days 6-13) of DnHP. No live pups were
      delivered. In a reproductive study, effects on fertility were noted in all
      treatment groups (380-1,670 mg/ kg body weight/day). These studies provided
      sufficient information in experimental animals to conclude that DnHP is a
      reproductive and developmental toxicant at the doses tested. However, the
      treatment doses were high and these studies did not determine an exposure level
      at which no adverse effects occur. Human exposure information for DnHP was not
      available to the panel. However, the panel assumed that the US general population
      would be exposed to 3-30 mug/kg body weight/day, based upon the range of
      estimated exposures for DEHP, a more widely used phthalate. Thus, considering the
      inadequate quantitative information from the experimental animal studies and the
      inadequate human exposure data, the panel concluded there is insufficient
      information to reach a conclusion of the potential for DnHP to adversely affect
      human development or reproduction. NTP-CERHR monographs are transmitted to
      federal and state agencies, interested parties, and the public and are available
      in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and
      in printed text or CD-ROM from the CERHR (National Institute of Environmental
      Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919
      316-4511).

PMID- 15995730
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Methanol.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for methanol to
      cause adverse effects on reproduction and development in humans. Methanol was
      selected for evaluation because it is a high production volume chemical with high
      potential for occupational, consumer, and environmental exposure. Methanol is
      used in chemical syntheses and as an industrial solvent. It is found in a variety
      of consumer products such as paints, antifreeze, cleaning solutions, and
      adhesives and is a by-product of sewage treatment, fermentation, and paper
      production. Methanol is used in racecar fuels, and there is the potential for the
      expanded use of methanol as a vehicle fuel or fuel additive. Methanol occurs
      naturally in a variety of fresh fruits and vegetables, alcoholic beverages, and
      cigarette smoke. The results of this evaluation on methanol are published in an
      NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report
      on the Reproductive and Developmental Toxicity of Methanol, and 3) public
      comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP
      reached the following conclusions regarding the possible effects of exposure to
      methanol on human development and reproduction. First, there is concern for
      adverse developmental effects in fetuses if pregnant women are exposed to levels
      of methanol that result in high blood concentrations, such as with acute methanol
      poisoning. Although there is insufficient evidence to determine if a human fetus
      is more or less sensitive than rodents to the adverse effect of methanol, humans
      suffering acute methanol poisoning may have blood levels similar to those
      resulting in developmental toxicity in rodents. Second, for exposures that result
      in low blood methanol concentrations (below approx. 10 mg/L blood), there is
      minimal concern for adverse developmental effects , and negligible concern for
      adverse male reproductive effects. There is insufficient evidence to assess the
      effects of methanol on female reproduction. Data available to the expert panel
      were not sufficient to rule out the possibility of male reproductive effects at
      toxic exposure levels. The panel judged that blood levels >/=10 mg/L are not
      expected to result from normal dietary or occupational exposures. NTP-CERHR
      monographs are transmitted to federal and state agencies, interested parties, and
      the public and are available in electronic PDF format on the CERHR web site
      (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR
      (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32,
      Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995731
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Fluoxetine.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for fluoxetine to
      cause adverse effects on reproduction and development in humans. Fluoxetine
      (Prozac(R); Serafemtrade mark) was selected for evaluation because of 1)
      sufficient reproductive and developmental studies, 2) human exposure information,
      3) changing prescription patterns, and 4) public concern about potential
      reproductive and/or developmental hazards associated with exposure. Fluoxetine,
      an antidepressant, is also prescribed to treat premenstrual dysphoric disorder
      and has recently been approved for use in 7-17 year-olds. The results of this
      evaluation on fluoxetine are published in an NTP-CERHR monograph which includes:
      1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and
      Developmental Toxicity of Fluoxetine, and 3) public comments received on the
      Expert Panel Report. As stated in the NTP Brief, the NTP reached the following
      conclusions regarding the possible effects of exposure to fluoxetine on human
      development and reproduction. First, there is some concern for developmental
      effects, specifically shortened gestation and poor neonatal adaptation at
      therapeutic doses (20-80 mg/day). This conclusion is based on evidence from human
      studies that fluoxetine produces an increased rate of poor neonatal adaptation
      and that fluoxetine exposure during pregnancy can result in a shortened gestation
      and reduced birth weight at term. Second, there is minimal concern for adverse
      reproductive effects in fluoxetine-exposed adults. Evidence from human studies
      show that therapeutic doses of fluoxetine may, in both men and women, result in
      reversible, impaired sexual function, specifically a delay in or an inability to
      achieve orgasm. Finally, there are insufficient data to draw conclusions on 1) an
      association between fluoxetine therapy in pregnant women and pregnancy loss; and
      2) on how breast milk or therapeutic exposures to fluoxetine might affect
      development. In a study in mice, early fluoxetine exposure affected adult
      behavior. However, additional data are needed to confirm and extend these
      findings and determine if such effects might possibly occur in humans. NTP-CERHR
      monographs are transmitted to federal and state agencies, interested parties, and
      the public and are available in electronic PDF format on the CERHR web site
      (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR
      (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32,
      Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995732
TI  - NTP-CERHR monograph on the potential human reproductive and developmental effects
      of acrylamide.
AB  - Acrylamide, used in the manufacture of polyacrylamide and grouting agents, is
      produced during the cooking of foods. Workplace exposure to acrylamide can occur
      through the dermal and inhalation routes. The objectives of this study were to
      evaluate the metabolism of acrylamide in humans following oral administration, to
      compare hemoglobin adduct formation on oral and dermal administration, to measure
      hormone levels, and to monitor the safety of acrylamide in people exposed under
      controlled conditions. Prior to conducting exposures in humans, a low-dose study
      was conducted in rats administered 3 mg/kg 1,2,3-13C3acrylamide by gavage. The
      study protocol was reviewed and approved by Institute Review Boards both at RTI
      which performed the sample analysis, and the clinical research center conducting
      the study. 1,2,3-13C3Acrylamide (AM) was administered in an aqueous solution
      orally (single dose of 0.5, 1.0,or 3.0 mg/kg) or dermally (3 daily doses of 3.0
      mg/kg) to sterile male volunteers. Urine samples (3 mg/kg oral dose) were
      analyzed for AM metabolites using 13C NMR spectroscopy. Approximately 86 % of the
      urinary metabolites were derived from GSH conjugation, and excreted as N-acetyl-S
      (3-amino-3-oxopropyl)cysteine and its S-oxide.Glycidamide, glycer amide, and low
      levels of N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine were detected in
      urine. On oral administration, a linear dose response was observed for N-(2
      carbamoylethyl)valine (AAVal) and N-(2-carbamoyl-2-hydroxyethyl)valine (GAVal) in
      hemoglobin. Dermal administration resulted in lower levels of AAVal and GAVal.
      This study indicated that humans metabolize acrylamide via glycidamide to a
      lesser extent than rodents, and dermal uptake was approximately 5%of that
      observed with oral uptake. Acrylamide is used in the manufacture of water-
      soluble polymers (European Union,2002). These polymers are then used for
      wastewater and sludge treatment, paper manufacture, soil stabilization, mining
      and many other uses (European Union, 2002).Acrylamide is also a chemical
      intermediate in the manufacture of other monomeric chemicals and used for
      grouting and preparation of laboratory gels for electrophoresis.Human exposure
      through these applications is very small (European Union, 2002).Previously, it
      has been postulated that dermal absorption was the major route of human exposure
      to acrylamide (European Union, 2002). The magnitude of this dermal absorption is
      highly relevant as one of the uses of acrylamide based polymers is in the
      formulation of skin creams (European Union, 2002). Estimates of dermal absorption
      based on in vitro and rodent studies have ranged from 3% to 100 (European
      Union,2002). Recently, exposure to acrylamide in a variety of cooked foods has
      been described(Rosen and Hellen as, 2002; Tareke et al., 2002). Human exposure
      via this route is substantial, with estimated exposures as high as 70 MUg per day
      proposed (Tareke et al.,2002). Acrylamide is metabolized by two main pathways:
      glutathione conjugation (Dixit et al.,1982; Edwards, 1975; Hashimoto and
      Aldridge, 1970; Miller et al., 1982; Sumner et al.,1992), and oxidation to
      glycidamide (Calleman et al., 1990; Sumner et al., 1992). The metabolism of
      acrylamide in vivo results in the formation of a number of metabolites.These
      metabolism of acrylamide in vivo has been investigated by administration of 1,2,3
      13C3 acrylamide to rodents, with the detection and quantitation of metabolites by
      13 CNMR spectroscopy (Sumner et al., 1999; Sumner et al., 1992; Sumner et al.,
      2003). The oxidation reaction to glycidamide is catalyzed by cytochrome P450 2E1
      in rodents(Sumner et al., 1999). Both acrylamide and glycidamide react with
      hemoglobin producing a stable adduct which can be measured as an indicator of
      exposure.Correlations have been made with hemoglobin adducts and neurotoxicity,
      but there has been no systematic standardization of hemoglobin adducts with dose.
      Glycidamide is weakly mutagenic in the Salmonella test (Hashimoto and Tanii,
      1985). It can react with DNA in vitro to produce a guanine derivative N7-(2
      carbamoyl-2-hydroxyethyl)guanine(Gamboa da Costa et al., 2003; Segerback et al.,
      1995). In vivo, administration of acrylamide to rats and mice produces low levels
      of N7-(2-carbamoyl-2-hydroxyethyl)guanine (Gamboa da Costa et al., 2003;
      Segerback et al., 1995).Acrylamide induces a characteristic peripheral
      neurotoxicity in animals and man(Spencer and Schaumburg, 1974a, b, 1975). This
      toxicity manifests itself as a distal to proximal loss of nerve function and
      dying back of cells. Acrylamide also effects rodent reproduction, namely smaller
      litter size. At elevated acrylamide doses other reproductive effects are seen,
      likely as a consequence of the neurotoxicity. Acrylamide is carcinogenic in
      drinking water studies in laboratory rats (Friedman et al.,1995; Johnson et al.,
      1986). In male rats, it induces tumors of the tunica vaginalis testes and the
      thyroid, while in females, it induces mammary fibroadenomas and thyroid
      tumors(Friedman et al., 1995). The mechanism for this tumorigenicity is unclear,
      although interaction with the dopamine receptor has been postulated as well as
      genotoxicity (Tyland Friedman, 2003). If the mechanism were genotoxicity, then
      conversion of acrylamide to glycidamide is directly proportional to carcinogenic
      activity.Understanding the mechanism of tumorigenicity is important, since
      conventional risk assessment techniques place the order of magnitude of the risk
      at approximately 10-3 with exposures of 70 MUg/ day.The relative contributions of
      acrylamide and glycidamide in the mode of action of acrylamide are the subject of
      debate and current research. Understanding the conversion of acrylamide to
      glycidamide and differences that may occur between species, exposure route, and
      dose are important considerations in assessing the risk of the possible effects
      of acrylamide exposures in the diet, in consumer products, and in the
      workplace.The primary objectives of this study were to evaluate the conversion of
      acrylamide to glycidamide in people exposed to acrylamide, and to evaluate the
      extent of uptake following dermal administration. This was conducted by
      administering a low dose of 13C labeled acrylamide to volunteers orally or
      dermally, and by measuring urinary metabolites or hemoglobin adducts derived from
      the glycidamide pathway and comparing them to metabolites and hemoglobin adducts
      derived from acrylamide directly. More specifically, we intended to evaluate
      urinary metabolites and hemoglobin adducts, and to measure hormone levels after
      exposure to a known dose of acrylamide. As a secondary and no less important
      objective, we intended to monitor the safety of acrylamide in people exposed
      under controlled conditions.

PMID- 15995733
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of 1-Bromopropane (1-BP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for 1-bromopropane
      to cause adverse effects on reproduction and development in humans. 1
      Bromopropane was selected for evaluation due to recent consideration of 1
      bromopropane as a replacement chemical for hydrochlorofluorocarbons and
      chlorinated solvents. 1-Bromopropane is used in spray adhesives and in cleaning
      metal and electronic components; as a solvent for fats, waxes, or resins; and as
      an intermediate in the synthesis of pharmaceuticals, insecticides, quaternary
      ammonium compounds, flavors, or fragrances. The results of this evaluation on 1
      brompropane are published in a NTP-CERHR monograph which includes: 1) the NTP
      Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity
      of 1-Bromopropane, and 3) public comments received on the Expert Panel Report. As
      stated in the NTP Brief, the NTP reached the following conclusions regarding the
      possible effects of exposure to 1-bromopropane on human development and
      reproduction. No data were available on 1-bromopropane exposures in the general
      US population. Therefore, conclusions were based on the available occupational
      exposure data and on studies in humans and laboratory animals. First, there is
      serious concern for reproductive and developmental effects at the upper end of
      the human occupational exposure range (18-381 ppm). Adverse developmental and/or
      reproductive effects have been reported in animal studies at exposure levels of
      >/=200 ppm. Second, there is minimal concern for reproductive and developmental
      effects when humans are exposed at the lower end of the human occupational
      exposure range (0.04-0.63 ppm). This level is at least 300- fold lower than the
      no effect level identified from reproductive studies in laboratory animals. These
      conclusions are based upon limited occupational inhalation exposure data. It is
      likely that worker exposures also occur through dermal contact with 1
      bromopropane. However, no information was available on dermal exposures. NTP
      CERHR monographs are transmitted to federal and state agencies, interested
      parties, and the public and are available in electronic PDF format on the CERHR
      web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the
      CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC
      32, Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995734
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of 2-Bromopropane (2-BP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for 2-bromopropane
      to cause adverse effects on reproduction and development in humans. 2
      Bromopropane was selected for evaluation due to documented evidence of worker
      exposures and published evidence of reproductive toxicity in both rodents and
      humans. 2-Bromopropane may be used as an intermediate in the synthesis of
      pharmaceuticals, dyes, and other organic chemicals. In Asia, 2-bromopropane was
      also used as a replacement for chlorofluorocarbons and 1,1,1-trichloroethane, and
      is used as a solvent/cleaner for microelectronics. The results of this evaluation
      on 2-brompropane are published in a NTP-CERHR monograph which includes: 1) the
      NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental
      Toxicity of 2-Bromopropane, and 3) public comments received on the Expert Panel
      Report. As stated in the NTP Brief, the NTP reached the following conclusions
      regarding the possible effects of exposure to 2-bromopropane on human development
      and reproduction. No data were available on environmental exposure of the general
      public to 2-bromopropane. However, occupational exposure data indicate workplace
      exposures to 2-bromopropane range from </=0.004- 1.35 ppm. Conclusions were based
      on the available occupational exposure data and on studies in humans and
      laboratory animals. First, there is some concern for adverse reproductive effects
      when people are exposed to concentrations of 2-bromopropane at the high end of
      the occupational exposure range, and minimal concern at the low end of the
      exposure range. These conclusions are supported by toxicity in rats at 100 ppm
      exposures and adverse reproductive effects in occupationally exposed humans.
      Second, there is insufficient evidence to assess the developmental effects of 2
      bromopropane exposure. These conclusions are based on occupational exposure data
      which do not account for dermal contact with 2-bromopropane. NTP-CERHR monographs
      are transmitted to federal and state agencies, interested parties, and the public
      and are available in electronic PDF format on the CERHR web site
      (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR
      (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32,
      Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995735
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Propylene Glycol (PG).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for propylene
      glycol (PG) to cause adverse effects on reproduction and development in humans.
      PG was selected for evaluation because of the potential for widespread human
      exposure through its use in food, tobacco, pharmaceutical products, cosmetics,
      various paints and coatings and as an antifreeze and de-icing solution. PG is a
      small, hydroxy-substituted hydrocarbon used as a chemical intermediate in the
      production of unsaturated polyester resins and in the production of plasticizers.
      The results of this evaluation on PG are published in an NTP-CERHR monograph
      which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive
      and Developmental Toxicity of Propylene Glycol, and 3) public comments received
      on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the
      following conclusions regarding the possible effects of exposure to PG on human
      development and reproduction. There is negligible concern for adverse
      developmental and reproductive effects in humans at current, proposed, or
      estimated exposure levels. There is no direct evidence that exposure of people to
      PG adversely affects reproduction or development. Studies in pregnant laboratory
      animals at oral doses of PG greater than 1,200 mg/kg body weight/ day and up to
      10,400 mg/kg body weight/day in mice, did not produce developmental toxicity in
      offspring. In a continuous breeding study, no effects on fertility were observed
      in male or female mice at doses up to 10,100 mg/kg body weight/day in drinking
      water. The pharmacokinetics of PG indicates that the lack of adverse effects
      observed in laboratory animals is relevant to humans. The rate-limiting step in
      PG metabolism is conversion to the more toxic lactaldehyde product by alcohol
      dehydrogenase. Studies indicate that this enzyme saturates in humans at doses 8
      10- fold lower than in rats and rabbits, thus affording less toxicity in humans.
      It is estimated that the average daily intake of PG from food products in the US
      is 34 mg/kg body weight/day for a 70 kg person, which is over 300 -fold lower
      than the highest dose tested in laboratory animals. NTP-CERHR monographs are
      transmitted to federal and state agencies, interested parties, and the public and
      are available in electronic PDF format on the CERHR web site
      (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR
      (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32,
      Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995736
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Di-n-Butyl Phthalate (DBP).
AB  - TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to
      Human Reproduction (CERHR) conducted an evaluation of the potential for di-n
      butyl phthalate (DBP) to cause adverse effects on reproduction and development in
      humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates
      Expert Panel. These phthalates were selected for evaluation because of high
      production volume, extent of human exposures, use in children's products, and/or
      published evidence of reproductive or developmental toxicity. Unlike many
      phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride
      plastics. DBP is a component of latex adhesives and is used in cosmetics and
      other personal care products, as a plasticizer in cellulose plastics, and as a
      solvent for dyes. The results of this evaluation on DBP are published in a NTP
      CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on
      the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3)
      public comments received on the Expert Panel Report. As stated in the NTP Brief,
      the NTP reached the following conclusions regarding the possible effects of
      exposure to DBP on human development and reproduction. First, although DBP could
      possibly affect human reproduction and development if exposures are sufficiently
      high, the NTP concludes that there is negligible concern for reproductive
      toxicity in exposed adults. Second, the NTP concludes that there is minimal
      concern for developmental effects when pregnant women are exposed to DBP levels
      estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence
      that exposure of people to DBP adversely affects reproduction or development, but
      studies reviewed by the expert panel show that oral exposure to high doses of DBP
      (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early
      postnatal development in rodents. Finally, based on exposure estimates in women
      of reproductive age, the NTP concludes that there is some concern for DBP causing
      adverse effects to human development, particularly development of the male
      reproductive system. NTP-CERHR monographs are transmitted to federal and state
      agencies, interested parties, and the public and are available electronically in
      PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text
      or CD-ROM from the CERHR (National Institute of Environmental Health Sciences,
      P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995737
TI  - NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects
      of Butyl Benzyl Phthalate (BBP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for butyl benzyl
      phthalate (BBP) to cause adverse effects on reproduction and development in
      humans. BBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates
      Expert Panel. These phthalates were selected for evaluation because of high
      production volume, extent of human exposures, use in children's products, and/or
      published evidence of reproductive or developmental toxicity. BBP is used in the
      production of vinyl tiles and polyvinyl chloride (PVC) to make products such as
      food conveyor belts, carpet tile, tarps, artificial leather, automotive trim, and
      traffic cones. The results of this evaluation on BBP are published in a NTP-CERHR
      monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the
      Reproductive and Developmental Toxicity of Butyl Benzyl Phthalate, and 3) public
      comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP
      reached the following conclusions regarding the possible effects of exposure to
      BBP on human development and reproduction. First, the NTP concludes there is
      negligible concern for adverse reproductive effects in exposed men. Data are
      insufficient to reach a conclusion on possible eproductive effects in exposed
      women. There is no direct evidence that exposure of people to BBP adversely
      affects reproduction or development, but studies reviewed by the expert panel
      show that oral exposure of laboratory animals to high doses (>/=1000 mg/kg body
      weight/day) of BBP can adversely affect development, including development of the
      male reproductive tract. Second, the NTP concludes that there is minimal concern
      for developmental effects in fetuses and children. Evidence showed adverse
      reproductive effects in rats at doses of 100 mg/kg body weight/day, but not at 20
      mg/kg/day. Exposure estimates for women of reproductive age were estimated to be
      7.8 mug/kg body weight/day. Therefore, this estimated exposure is at least 2,500
      to 25,000- fold lower than the toxic dose in rats. NTP-CERHR monographs are
      transmitted to federal and state agencies, interested parties, and the public and
      are available in electronic PDF format on the CERHR web site
      (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR
      (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32,
      Research Triangle Park, NC; fax: 919-316-4511).

PMID- 15995738
TI  - Chemical science in China.
AB  - Articles from China are showcased across RSC journals this month, in recognition
      of the growing importance of Chinese research in the Chemical Sciences.

PMID- 15995739
TI  - Synthesis of mixed-donor amido/amino/siloxo ligands from symmetrical
      diamidosilylether ligands via a retro-Brook rearrangement and their chromium(II)
      complexes.
AB  - The dilithio salts of two chelating diamidosilylether ligands undergo a retro
      Brook rearrangement from oxygen to the amido-nitrogen, thereby directly yielding
      a new mixed-donor amido/amino/siloxo ligand. When reacted with chromium(II),
      siloxo-bridged dimers and a very strong eta(2)-(N,C(ipso)) arylamido interaction
      are featured.

PMID- 15995740
TI  - Self-assembly of coordination molecular baskets as inorganic analogues of
      cyclotriveratrylenes (CTV).
AB  - A [3 + 3] modular self-assembly gives rise to the formation of basket-shaped,
      crown ether-functionalized, nano-sized trimetallo-macrocycles, which function as
      structural analogues of cyclotriveratrylenes (CTV).

PMID- 15995741
TI  - Synthesis and characterization of a Mo/Ag/Rb heterotrimetallic cluster with
      double-cage architecture.
AB  - The first Mo/Ag/Rb heterotrimetallic cluster has been synthesised by a self
      assembly reaction involving [Mo2O2S2edt2]2-, Ag+, Rb+, S2- and dibenzo-18-crown-6
      (DB18C6); the structure consists of two [{Mo6Ag6O6S7edt6}2{Rb(DB18C6)}]3- units
      linked by Rb-C contacts.

PMID- 15995742
TI  - Donor effect on supramolecular structures of silver(I) perchlorate complexes of
      macrocycles with O2S2X (X=S, O and NH) donor sets.
AB  - By virtue of simple one donor variations of O(2)S(2)X-donor macrocycles (L(1):
      X=S, L(2): X=O and L(3): X=NH) towards silver(I) perchlorates, four
      supramolecular complexes (1-3) with different topologies have been isolated; L(1)
      afforded solvent- and anion-free sandwich complex (1), otherwise L(2) and L(3)
      gave the dimeric (2a), 1-D polymeric (2b), and tetrameric bowl-type (3) complexes
      with solvent or anion coordination.

PMID- 15995743
TI  - Isomeric [RuCl2(dmso)2(indazole)2] complexes: ruthenium(II)-mediated coupling
      reaction of acetonitrile with 1H-indazole.
AB  - Reaction of the antitumor complex trans-[Ru(III)Cl4(Hind)2]- (Hind = indazole)
      with an excess of dimethyl sulfoxide (dmso) in acetone afforded the complex
      trans,trans,trans-[Ru(II)Cl2(dmso)2(Hind)2] (1). Two other isomeric compounds
      trans,cis,cis-[Ru(II)Cl2(dmso)2(Hind)2] (2) and cis,cis,cis
      [Ru(II)Cl2(dmso)2(Hind)2] (3) have been obtained on refluxing cis
      [Ru(II)Cl(2)(dmso)(4)] with 2 equiv. of indazole in ethanol and methanol,
      respectively. Isomers 1 and 2 react with acetonitrile yielding the complexes
      trans-[Ru(II)Cl2(dmso)(Hind){HN=C(Me)ind}].CH3CN (4.CH3CN) and trans,cis
      [Ru(II)Cl2(dmso)2{HN=C(Me)ind}].H2O (5.H2O), respectively, containing a cyclic
      amidine ligand resulting from insertion of the acetonitrile C triple bond N group
      in the N1-H bond of the N2-coordinated indazole ligand in the nomenclature used
      for 1H-indazole. These are the first examples of the metal-assisted
      iminoacylation of indazole. The products isolated have been characterized by
      elemental analysis, IR spectroscopy, UV-vis spectroscopy, electrospray mass
      spectrometry, thermogravimetry, differential scanning calorimetry, 1H NMR
      spectroscopy, and solid-state 13C CP MAS NMR spectroscopy. The isomeric
      structures of 1-3 and the presence of a chelating amidine ligand in 4 and 5 have
      been confirmed by X-ray crystallography. The electrochemical behavior of 1-5 and
      the formation of 5 have been studied by cyclic voltammetry.

PMID- 15995744
TI  - Platinum(II) 1,10-phenanthroline complexes of acetylides containing redox-active
      groups.
AB  - The new diimine ligand 3,8-di-n-pentyl-4,7-di(phenylethynyl)-1,10-phenanthroline
      (1) was used for the synthesis of a range of Pt(II) complexes, viz.[Pt(1)Cl2],
      [Pt(1)(C triple bond C-Ph)2], [Pt(1)(C triple bond C-Fc)2] and [Pt(1)(C triple
      bond C-p-C6H4-C triple bond C-Fc)2](Fc = ferrocenyl). Crystal structure analyses
      were performed for [Pt(1)Cl2] and [Pt(1)(C triple bond C-Ph)2] and revealed that
      the di(acetylide)pi-tweezer of the latter binds a molecule of chloroform through
      C-H...pi hydrogen bonds. The redox and optical properties of 1 and its complexes
      were investigated by (spectro-)electrochemistry, UV-Vis and luminescence
      spectroscopy, and an energy level diagram was derived for [Pt(1)(C triple bond C
      Fc)2] and related compounds on the basis of the data collected. The ferrocenyl
      substituted Pt(II) complexes are donor-sensitiser assemblies. Intramolecular
      quenching of the photoexcited Pt(II) diimine unit leads to very short
      luminescence lifetimes for [Pt(1)(C triple bond C-p-C(6)H(4)-C triple bond C
      Fc)2](2 ns) and [Pt(1)(C triple bond C-Fc)2](0.3 ns), as opposed to [Pt(1)(C
      triple bond C-Ph)2](0.7 micros). Excimer formation has been observed for [Pt(1)(C
      triple bond C-Ph)(2)] at room temperature in dichloromethane and at low
      temperatures in frozen glassy dichloromethane and 2-methyltetrahydrofuran
      solution, but not in the solid state.

PMID- 15995745
TI  - Synthesis and structural characterization of mono- and bisfunctional o
      carboranes.
AB  - Functionalized o-carboranes are interesting ligands for transition metals.
      Reaction of LiC2B10H11 with Me2NCH2CH2Cl in toluene afforded 1-Me2NCH2CH2-1,2
      C2B10H11 (1). Treatment of 1 with 1 equiv. of n-BuLi gave
      [(Me2NCH2CH2)C2B10H10]Li ([1]Li), which was a very useful synthon for the
      production of bisfunctional o-carboranes. Reaction of [1]Li with RCH2CH2Cl
      afforded 1-Me2NCH2CH2-2-RCH2CH2-1,2-C2B10H10 (R = Me2N (2), MeO (3)). 1 and 2
      were also prepared from the reaction of Li2C2B10H10 with excess Me2NCH2CH2Cl.
      Treatment of [1]Li with excess MeI or allyl bromide gave the ionic salts, [1
      Me3NCH2CH2-2-Me-1,2-C2B10H10][I] (4) and [1-Me2N(CH2=CHCH2)CH2CH2-2-(CH2=CHCH2)
      1,2-C2B10H10][Br] (6), respectively. Interaction of [1]Li with 1 equiv. of allyl
      bromide afforded 1-Me2NCH2CH2-2-(CH2=CHCH2)-1,2-C2B10H10 (5). Treatment of [1]Li
      with excess dimethylfulvene afforded 1-Me2NCH2CH2-2-C5H5CMe2-1,2-C2B10H10 (7).
      Interaction of [1]Li with excess ethylene oxide afforded an unexpected product 1
      HOCH2CH2-2-(CH2=CH)-1,2-C2B10H10 (8). 1 and 3 were conveniently converted into
      the corresponding deborated compounds, 7-Me2NHCH2CH2-7,8-C2B9H11 (9) and 7
      Me2NHCH2CH2-8-MeOCH2CH2-7,8-C2B9H10 (10), respectively, in MeOH-MeOK solution.
      All of these compounds were characterized by various spectroscopic techniques and
      elemental analyses. The solid-state structures of 4 and 6-10 were confirmed by
      single-crystal X-ray analyses.

PMID- 15995746
TI  - Unusual structural and energetic features of homolytic bond dissociation: from
      tetrakis(disyl)diphosphine to tetrakis(di-tert-butylsilyl)hydrazine.
AB  - Quantum chemical calculations of the structures and thermodynamics of homolytic
      dissociation of the central P-P and N-N bonds in tetrakis(disyl)diphosphine and
      tetrakis(di-tert-butylsilyl)hydrazine have been performed. The theory predicted
      negative standard enthalpies for homolytic bond dissociation in both cases, -71.0
      and -108.4 kJ mol(-1) for the diphosphine and hydrazine, respectively, using the
      ONIOM (MP2/6-31+G*:B3LYP/3-21G*) level. The dissociation is accompanied by
      considerable structural changes in the radicals as compared to the corresponding
      fragments of the parent molecules, resulting in low dissociation enthalpies. The
      most pronounced changes in both radicals are the relaxation of bond angles in the
      substituents and a conformational change in the orientation of the substituent
      groups. In addition, the bis(di-tert-butylsilyl)aminyl radical displays a
      considerable increase in Si-N-Si angle and shortening of the Si-N bonds upon
      dissociation. These changes are not associated with any appreciable
      delocalisation of the lone electron, as the spin density is found from the
      B3LYP/3-21G* calculations to be largely concentrated on the nitrogen atom. It has
      been also shown that although the dissociation energies are low for both
      compounds, the intrinsic energies of the central bonds are still high, 140.6 kJ
      mol(-1) for the P-P bond in tetrakis(disyl)diphosphine and 490.6 kJ mol(-1) for
      the N-N bond in tetrakis(di-tert-butylsilyl)hydrazine, using the ONIOM method.
      The calculations predict that the dissociation of tetrakis(disyl)diphosphine
      would have negative free energy even without taking relaxation of the fragments
      into account, while the full potential of releasing about 306 kJ mol(-1) of
      energy stored in the ligands of tetrakis(di-tert-butylsilyl)hydrazine is only
      fully realised upon a considerable separation of the fragments.

PMID- 15995747
TI  - Synthesis and structures of 5-(pyridyl)tetrazole complexes of Mn(II).
AB  - New Mn(II) complexes containing 5-(2-pyridyl)tetrazole, 5-(3-cyano-4
      pyridyl)tetrazole or 5-(4-pyridyl)tetrazole ligands are described. The complexes
      are prepared by reaction of the corresponding cyanopyridines with sodium azide in
      the presence of Mn(II) salts. All the complexes have been characterized by X-ray
      crystallography, which reveals that 5-(pyridyl)tetrazole ligands can coordinate
      to Mn through either type of nitrogen atom in the tetrazole residue or via the
      pyridyl group. In the solid state, extended 2D and 3D structures are produced
      through networks of hydrogen bonding (involving water molecules and the
      tetrazolate residue). Acidification of the complexes produces the corresponding
      free 5-(pyridyl)-1H-tetrazole.

PMID- 15995748
TI  - Kinetics and mechanism of the reactions of [FeCl4]- with PhS- or PhSH in MeCN,
      and the role of cations containing N-H groups.
AB  - The kinetics of the reactions between [FeCl4]- and an excess of PhS- have been
      studied using stopped-flow spectophotometry. The associated absorbance-time
      curves can be fitted to two exponentials, and these first and second phases
      correspond to the formation of [FeCl3(SPh)]- and [FeCl2(SPh)2]-, respectively. It
      seems likely that the steps involving formation of [FeCl(SPh)3]- and [Fe(SPh)4]-
      are associated with much smaller changes in absorbance and so are not detected.
      The kinetics of the first phase exhibit a non-linear dependence on the
      concentration of PhS- indicating an associative mechanism in which PhS- rapidly
      binds to [FeCl4]- to form [FeCl4(SPh)]2- prior to rate-limiting dissociation of
      chloride and formation of [FeCl3(SPh)]-. The kinetics indicate that at high
      concentrations of PhS-, the five-coordinate intermediate attains stoichiometric
      concentrations. This is confirmed by the spectroscopic changes. The second phase
      shows analogous kinetics. The kinetics of the reactions between [FeCl4]- and an
      excess of PhSH have also been studied. For the first phase the reaction occurs at
      a rate independent of the concentration of PhSH, consistent with an associative
      mechanism in which the solvent (MeCN) is the nucleophile to form [FeCl3(NCMe)].
      Subsequent rapid replacement of the coordinated solvent by PhSH yields
      [FeCl3(SHPh)]. The kinetics of the second phase of the reaction with PhSH
      exhibits a non-linear dependence on the concentration of PhSH, analogous to the
      kinetics observed with PhS- and consistent with an associative mechanism. The
      cations [NHEt3]+, [NH2Et2]+ and [lutH]+ (lut = 2,6-dimethylpyridine) form ion
      pairs with [FeCl4]- which undergo substitution more rapidly than free [FeCl4]-.

PMID- 15995749
TI  - Cascade complexation: a single cyano bridge links a pair of Cu(II) cations.
AB  - A series of structurally characterised mu-cyanodicopper(II) cryptates shows
      moderately strong antiferromagnetic interaction in the range -2J= 150-200 cm(-1),
      at the high end of the observed range for such assemblies. The lowest magnetic
      exchange coupling parameter is displayed where there is slight bending of the M
      CN-M assembly, enforced by the constraints of cryptate encapsulation. Thermally
      accessible triplet EPR spectra are observed with zero-field splittings of the
      order of 0.13-0.14 cm(-1), confirming collinear ground-state dz2 orbitals for
      Cu(II), consistent with their trigonal-bipyramidal coordination geometries.

PMID- 15995750
TI  - Tris(mercaptoimidazolyl)borate complexes of the coinage metals: syntheses and
      molecular structures of the first gold compounds and related copper and silver
      derivatives.
AB  - The first tris(mercaptoimidazolyl)borate complexes of gold, Au(Tm(tBu)) and
      (Tm(tBu))Au(PPh3), have been prepared and structurally characterized. Together
      with their copper and silver analogues M(Tm(tBu)) and (Tm(tBu))M(PPh3)(M = Cu,
      Ag), these compounds constitute the first two complete series of Tm(R)
      derivatives to be isolated for the coinage metals. In order to evaluate the
      steric and electronic effects of the bulky tert-butyl substituents in these
      species, comparative structural analyses with the known methyl-substituted
      analogue Ag(Tm(Me)) and various (Tm(Me))M(PR3) derivatives (M = Cu, Ag) are also
      presented.

PMID- 15995751
TI  - Novel spectral and electrochemical characteristics of triphenylamine-bound zinc
      porphyrins and their intramolecular energy and electron transfer.
AB  - Porphine bearing triphenylamine (TPA) pendant groups and their zinc complexes,
      zinc meso-tetra-p-(di-p-phenylamino)phenylporphyrin (ZnTDPAPP) and zinc meso
      tetra-p-(di-p-tolylamino)phenylporphyrin (ZnTDTAPP) are synthesized and their
      spectral and electrochemical characteristics are studied. Zinc meso
      tetraphenylporphyrin (ZnTPP) and zinc meso-tetra-p-aminophenylporphyrin (ZnTAPP)
      are also used as reference complexes. The B and Q bands of ZnTDPAPP and ZnTDTAPP
      are located at higher wavelengths and the bandwidths become broader compared with
      those of ZnTPP and ZnTAPP, indicating the peripheral TPA affects the electronic
      configuration of zinc porphyrins. Upon excitation in CH2Cl2 at room temperature,
      the compounds exhibit intramolecular singlet energy transfer from the TPA to the
      porphyrin core, and emission from the porphyrins are observed. Both ZnTDPAPP and
      ZnTDTAPP are easier to be oxidized and harder to be reduced than ZnTPP, in
      agreement with the strong electron-donating effect of the TPA groups. Extra waves
      corresponding to the oxidation of TPA substituents are also observed. The cation
      radical ZnTDTAPP+* exhibits an absorption spectrum very different from the
      typical spectra for porphyrin cation radicals. The NIR absorption band at 1296 nm
      indicates the electron transfer occurs intramolecularly. The above results evince
      the ability of TPA to modulate the electronic structure of zinc porphyrins.

PMID- 15995752
TI  - Solvent effect on the adduct formation of methyltrioxorhenium (MTO) and pyridine:
      enthalpy and entropy contributions.
AB  - 1:1 adduct formation between methyltrioxorhenium (MTO) and pyridine in different
      solvents (n-hexane, benzene, chloroform, ethyl acetate, dichloromethane and
      acetone) was studied using spectrophotometric techniques. The formation constants
      were determined from the absorbance change of the adduct versus pyridine
      concentration. The values of the formation constants vary from 114.5 to 752.5 L
      mol(-1) at T= 20 degrees C depending on the dielectric constant of the solvent
      (epsilon(r) = 1.89-20.7). Enthalpy and entropy changes during the adduct
      formation reactions were determined from van't Hoff plots. The measured enthalpy
      change of -37.0 to -22.2 kJ mol(-1) depends on epsilon(r), which is explained by
      Onsager's reaction field theory. The measured entropy change ranges from -71.2 to
      -36.6 J K(-1) mol(-1), and the dependence on the solvent is discussed in terms of
      the solvation effect.

PMID- 15995753
TI  - Versatility of 2,6-diacetylpyridine (dap) hydrazones in stabilizing uncommon
      coordination geometries of Mn(II): synthesis, spectroscopic, magnetic and
      structural characterization.
AB  - Five seven- or eight-coordinate manganese complexes of hydrazone ligands have
      been prepared. Three seven-coordinate neutral Mn(II) complexes: [Mn(dapA2)]n (1),
      [Mn(dapB2)(H2O)2] (2), [Mn(dapS2)(H2O)2] (3) have been synthesized from the bis
      Schiff bases of 2,6-diacetylpyridine: dap(AH)2, dap(BH)2 and dap(SH)2 (AH =
      anthraniloyl hydrazide, BH = benzoyl hydrazide, SH = salicyloyl hydrazide),
      respectively. Two eight-coordinate Mn(II) complexes: [Mn(dapS)2] (4) and
      [Mn(dapB)2].3H2O (5) have been synthesized from the mono-Schiff bases dapBH and
      dapSH, respectively. The complexes have been characterized by elemental analyses
      and by IR, UV-Vis., FAB mass, EI mass and EPR spectroscopy. The molecular
      structures of 1, 3.DMF and 4.DMF have been determined by single-crystal X-ray
      diffraction. The mono-Schiff bases are monoanionic and the bis-Schiff bases are
      dianionic. The octa-coordinated mono-Schiff base complex 4 adopts a dodecahedral
      geometry, while the hepta-coordinated bis-Schiff base complex 1 forms a one
      dimensional linear polymeric chain. A weak antiferromagnetic exchange interaction
      (J=-0.15 cm(-1)) between the Mn(II) ions in is attributed to weak Mn...Mn
      interaction through the PhNH(2) moiety of the ligand, as indicated by extended
      Huckel molecular orbital calculations. A good simulation of the EPR spectrum of a
      frozen solution (DMSO at 4 K) of compound 1 was obtained with g=2.0, D=0.1 cm(
      1), E=0.01 cm(-1). The EPR spectrum of a powdered sample of compound 1 shows a
      large broadening of the signal, due in part, to the important zero-field
      splitting of the hepta-coordinated Mn(II) ion.

PMID- 15995754
TI  - An artificial siderophore for the detection of iron(III).
AB  - An artificial siderophore in the form of a squaraine dye (1) has been
      synthesized. The bidentate ligand chelates to Fe(III) between the deprotonated
      hydroxyl group on the ortho position of the ring adjacent to the carbonyl group
      of the cyclobutadiene ring. The optical response is due to a subtle geometry
      change of 1 on chelation to Fe(III). This artificial siderophore forms a 2 ratio
      1 ligand ratio metal complex, as indicated by a sigmoidal isotherm (K(a)= 10(7)
      M(-1)). The optical response on the addition of Fe(III) is observed at low
      concentrations in comparison to other metal salts. The X-ray crystal structure
      and calculated structures of dye (1) are also included, and will be discussed.

PMID- 15995755
TI  - Multidentate aryloxide and oxo-aryloxide complexes of antimony: synthesis and
      structural characterization of [eta4-N(o-C6H4O)3]Sb(OSMe2), {{[eta3-N(o-C6H4OH)-
      (o-C6H4O)2]Sb}2(mu2-O)}2 and {[eta3-PhN(o-C6H4O)2]Sb}4(mu3-O)2.
AB  - Antimony compounds that feature multidentate aryloxide ligands, namely [eta4-N(o
      C6H4O)3]Sb(OSMe2), {{[eta3-N(o-C6H4OH)(o-C6H4O)2]Sb}2(mu2-O)}2, and {[eta3-PhN(o
      C6H4O)2]Sb}4(mu3-O)2 have been synthesized from N(o-C6H4OH)3 and PhN(o-C6H4OH)2
      and structurally characterized by X-ray diffraction. While [eta4-N(o
      C6H4O)3]Sb(OSMe2) exists as a discrete mononuclear species, the oxo complexes
      {{[eta3-N(o-C6H4OH)(o-C6H4O)2]Sb}2(mu2-O)}2 and {[eta3-PhN(o-C6H4O)2]Sb}4(micro3
      O)2 are multinuclear. Specifically, the dinuclear fragment {[eta3-N(o-C6H4OH)(o
      C6H4O)2]Sb}2(mu2-O)} exists in a dimeric form due to the bridging oxo ligand
      participating in an intermolecular hydrogen bonding interaction, while the
      dinuclear fragment {[eta3-PhN(o-C6H4O)2]Sb}2(mu-O) exists in a dimeric form due
      to the bridging oxo ligand serving as a donor to the antimony of a second
      fragment. The structures of {{[eta3-N(o-C6H4OH)(o-C6H4O)2]Sb}2(mu2-O)}2 and
      {[eta3-PhN(o-C6H4O)2]Sb}4(mu3-O)(2), therefore, indicate that an oxo ligand
      bridging two Sb(III) centers is sufficiently electron rich to serve as both an
      effective hydrogen bond acceptor and as a ligand for an additional Sb(III)
      center.

PMID- 15995756
TI  - Dimetallic complexes of a structurally versatile pyridazine-containing Schiff
      base macrocyclic ligand with pendant pyridine arms.
AB  - The new [2 + 2] Schiff-base macrocyclic ligand L2, containing pyridazine head
      units and pyridine pendant arms, was synthesised as [Ba(II)2L2(ClO4)4(OH2)] 1
      from the barium(II) ion templated condensation reaction of 3,6-diformylpyridazine
      and N1-(2-aminoethyl)-N1-(methylene-2-pyridyl)-ethane-1,2-diamine. Subsequent
      transmetallation reactions of 1 with copper(II), iron(II) and manganese(II)
      perchlorates led to the formation of [Cu(II)2L2](ClO4)4.2MeCN 2,
      [Fe(II)2L2(MeCN)2](ClO4)4 3 and two manganese complexes, 4 and 5, with the same
      formula, [Mn(II)2L2(MeCN)(OH2)](ClO4)4, but slightly different crystal
      structures, respectively. Single-crystal X-ray structural analyses reveal the
      variety of structures which can be supported by L2 in order to meet the
      coordination environment preferences of the incorporated metal ions. The
      barium(II) ions in 1 have an irregular ten-coordinate geometry whereas the
      copper(II) ions in 2 have a square pyramidal geometry and the iron(II) ions in 3
      have an octahedral geometry, while in 4 and 5 every manganese(II) ion is seven
      coordinate and the environment can be best described as distorted pentagonal
      bipyramidal. In 1, 4 and 5 the pyridazine moieties bridge the metal centres
      [Ba(1)...Ba(2) 4.9557(3)A 1; Mn(1)...Mn(2) 4.520(1)A 4; Mn(1)[dot dot dot]Mn(2)
      4.3707(8)A 5] but this is not observed in the copper(II) and iron(II) complexes,
      2 and 3, in which the metal ions are well separated [Cu(1)...Cu(2) 5.9378(6)A 2;
      Fe(1)...Fe(2) 5.7407(12)A 3]. In the cyclic voltammogram of
      [Cu2(II)L2](ClO4)4.2MeCN 2 in MeCN vs. Ag/AgCl two separate reversible one
      electron transfer steps are observed [E(1/2)=0.04 V, DeltaE= 0.12 V and E(1/2)=
      0.20 V, DeltaE=0.12 V; K(c)=510; in this system E(1/2)(Fc+/Fc)=0.42 V and
      DeltaE(Fc+/Fc)=0.08 V]. The other complexes cannot be reversibly
      reduced/oxidised.

PMID- 15995757
TI  - Anion and cation binding by a pendant arm cyclam and its macrobicyclic
      derivatives.
AB  - A series of transition-metal complexes of N,N',N'',N'''-tetra(3
      hydroxypropyl)cyclam (L1) are reported. The X-ray structures of the compounds
      reveal pendant arm coordination of one of the alcohol groups to give square
      pyramidal metal centres with simultaneous hydrogen bonding to the counter anions.
      Ligand L1 has been elaborated to form a series of macrotricyclic derivatives that
      form 1 ratio 1 complexes with Cu(II) and Ni(II). The X-ray structure of the
      tetrahydrate and protonated forms of L1 are also reported.

PMID- 15995758
TI  - [(Benzimidazol-1-yl)methyl]benzamides as bifunctional reagents for reliable
      inorganic-organic supramolecular synthesis.
AB  - A series of ligands that utilize five-membered N-heterocycles as coordination
      sites, and the self-complementarity of the carboxamide functionality, have been
      employed in the supramolecular synthesis of Ag(I)-based extended networks. The
      crystal structures of eight compounds are reported: bis[4-(2-methylbenzimidazol-1
      yl)methylbenzamide]silver(I) tetrafluoroborate hydrate methanol, 1; bis[3-(2
      methylbenzimidazol-1-yl)methylbenzamide]silver(I) tetrafluoroborate, 2; bis[4
      (5,6-dimethylbenzimidazol-1-yl)methylbenzamide]silver(I) tetrafluoroborate, 3;
      bis[4-(2-methylbenzimidazol-1-yl)methylbenzamide]silver(I) hexafluoroarsenate
      methanol, 4; bis[3-(2-methylbenzimidazol-1-yl)methylbenzamide]silver(I)
      hexafluoroarsenate methanol(0.5), 5; bis[4-(5,6-dimethylbenzimidazol-1-yl)
      methylbenzamide]silver(I) hexafluoroarsenate, 6; bis[4-(2-methylbenzimidazol-1
      yl)methylbenzamide]silver(I) hexafluoroantimonate, 7; and bis[3-(2
      methylbenzimidazol-1-yl)methylbenzamide]silver(I) hexafluoroantimonate, 8. An
      analysis of motifs and structural patterns that result from the primary
      intermolecular interactions in these structures, reveals that this family of
      ligands is capable of providing quite reliable means for propagating the linear
      geometry of the complex ions into extended 1-D architectures via ligand-ligand, N
      H...O, hydrogen-bond interactions.

PMID- 15995759
TI  - [Strengthen the scientific research on oral hereditary diseases].
AB  - There are many kinds of oral hereditary diseases. Although some attempts have
      been tried to find the genetics of those diseases, still fewer information are
      available than the other hereditary diseases at present. Much is needed to do in
      the future. This article reviewed some cutting-edge findings on the genetics of
      several oral hereditary diseases including hereditary diseases involving the
      teeth, periodontal tissues, soft and hard tissues of the oral and maxillofacial
      region, as well as cleft lip and palate.

PMID- 15995760
TI  - [Zygomatic implants anchorage for the rehabilitation of maxillary defects].
AB  - PURPOSE: Prosthetic reconstruction of the upper jaw in patients with extensive
      bone and soft tissue defects is still a significant challenge. This study
      evaluated the functional results of zygomatic implants and vascularized bone
      graft reconstruction of the maxillary defects in 4 patients. METHODS: Complex
      resections of the maxilla produced a three-dimensional defect in 4 patients. On
      the basis of an axial spiral CT data, anatomical models of natural size by
      CAD/CAM system was manufactured to enable preoperative measurements of relevant
      parameters. After tumor resection, reconstruction using the fibula or iliac
      osteocutaneous flap with titanium osseointegrated implants was performed.
      Maxillary and zygomatic measurements were also used to obtain information for
      installing 6 zygomatic implants and 7 dental implants. RESULTS: The bone from the
      fibula or iliac osteocutaneous flap was contoured to recreate the maxillary arch
      in 4 patients. The anatomical model and surgical palate was used for preoperative
      planning and intraoperative control of the insertion of 6 zygomatic fixtures
      after subtotal maxillectomy. The implants could be positioned precisely as
      preoperatively planned. CONCLUSIONS: The use of zygomatic fixtures after ablative
      tumor surgery with resection of the maxillary bone is valuable in providing new
      zygomatic buttresses that play a key role in the form of the midface. Maxillary
      rehabilitation can be further improved by using the vascularized bone graft and
      zygomatic implants. Reconstitutions of the buttresses system ensure a stable base
      for occlusion, which is essential to optimal functional and esthetic maxillary
      rehabilitation. Supported by Research Fund (No. 2004BA720A27) of National Tenth
      Five-Year Project.

PMID- 15995761
TI  - [Esthetic augmentation using connective tissue and bone graft harvested from
      implantation bed].
AB  - PURPOSE: To describe a surgical method of using connective tissue graft and bone
      graft harvested from implantation bed to restore the labial contour. METHODS: 102
      ITI system implants were placed in 55 anterior maxilla, with connective tissue
      graft and bone graft harvested from implantation bed simultaneously.
      Suprastructure restorations were performed at least 6 weeks later, and the change
      of the labial contour was evaluated. RESULTS: The labial contour was greatly
      improved, and the esthetics around the implants were enhanced. CONCLUSIONS: Using
      free connective tissue and bone graft harvested from implantation bed could
      achieve an esthetic outcome. It is cost-effective and deserves popularization.
      Supported by Research Fund (No.034119872) of Science and Technology Commission of
      Shanghai Municipality.

PMID- 15995762
TI  - [The study of maxillary protraction face mask combined with orthodontics for
      complete unilateral cleft lip and palate patients].
AB  - PURPOSE: The purpose of this study was to evaluate the influence of maxillary
      protraction face mask combined with orthodontics on complete unilateral cleft lip
      and palate patients' jaws. METHODS: 14 patients with complete unilateral cleft of
      lip and palate were included. Lateral cephalometric films were taken before
      orthodontic treatment ,before protracting and after orthodontic treatment. The
      statistical data were compared and analysed by SPSS10.0. Student's t test was
      used to determine the effect of maxillary protraction face mask combined with
      orthodontic treatment on jaw growth before and after treatment. RESULTS: The
      treatment resulted in good outcomes: incisor's overjet of 2mm, stable occlusion
      and straight profile. The SNA angle had a significant increase (P<0.001). The SNB
      angle and mandibular plane angle (SN-MP) have no change (P>0.05). The convexity
      of angle had significant change (P<0.001). CONCLUSION: Orthopedic force combined
      orthodontic treatment on patients with UCLP can promote the development of
      maxilla, without significant effect on the mandible. The overjet and overbite
      were improved by increasing the clination of upper anterior teeth, compensating
      lingually on lower anterior teeth and moving the upper anterior forward. The
      profile was improved from concave to straight, maxillary protrusion was
      increased, upper lip was plumpand, and the relationship between upper and lower
      jaws was more compatible.

PMID- 15995763
TI  - [Diagnosis and treatment of 23 cases with stylohyoid syndrome].
AB  - PURPOSE: To assess the diagnosis and treatment of stylohyoid syndrome. METHODS:
      The clinical data of 23 patients with stylohyoid syndrome were analyzed
      retrospectively,the symptoms,age,gender, length of styloid process, and clinical
      signs were investigated in their relationship to the disease onset , the value of
      styloidectomy via transoral and extraoral approach was compared. RESULTS: (1)
      Pain and foreign body sensation in oropharyngeal area accounted for 83%(19/23) of
      the symptoms ,followed by 43%(10/23) of headache, tongueache and periauricular
      discomfort. (2) Females were more often affected than males. The age peak was 50s
      and 30s ,accounting for 43%(10/23) and 30%(7/23) respectively. (3) 91%(21/23) of
      the excised styloid processes were longer than 3cm in length, 9% (2/23) of them
      shorter than 3cm but with abnormality in shape. (4) 57%(13/23) of the elongated
      styloid processes could be palpated transorally. (5) Through extraoral approach,
      all kinds of diseased styloid processes could be excised thoroughly and safely.
      CONCLUSIONS: Stylohyoid syndrome is one of the causes of head and neck pain. A
      complete medical history , careful palpation of the oral pharyngeal area, and
      radiographic examination are essential for the diagnosis. Styloidectomy by
      extraoral approach is effective for curing of the disease.

PMID- 15995764
TI  - [Surgical treatment of obstructive sleep apnea hypopnea syndrome after
      velopharyngeal ring ligation procedure].
AB  - PURPOSE: To evaluate the effect of removal of ligation thread combined
      adenoidectomy in the treatment of obstructive sleep apnea hypopnea syndrome
      (OSAHS) after velopharyngeal ring ligation procedure (VRLP). METHODS: The upper
      airway was examined with dynamic fiberoptic pharyngoscope in six patients with
      cleft palate who were diagnosed as OSAHS by polysomnography(PSG) after VRLP. All
      the patients underwent removal of ligation thread and adenoidectomy. Three months
      after operation, they were recalled back and were examined with polysomnography
      and dynamic fiberoptic pharyngoscope. The preoperative and postoperative PSG data
      were analysed with t test and chi-square test to determine the statistical
      differences. RESULTS: In patients with OSAHS after VRLP, a ring scar was observed
      on the upper airway at the soft palate level and a remarkable narrow
      nasopharyngeal meatus was found mainly because of adenoidal hypertrophy. After
      removal of ligation thread and adenoidectomy, no velopharyngeal incompetence was
      found, the upper airway morphology was smooth, respiration disorder during
      sleeping was completely disappeared and sleep architecture became normal. There
      were significant differences between preoperative and postoperative PSG data.
      CONCLUSION: Removal of ligation thread combined adenoidectomy was an effective
      treatment for OSAHS after VRLP.

PMID- 15995765
TI  - [Clinical observation of treating nonrestorable teeth with orthodontics,
      periodontal therapy and prosthodontics].
AB  - PURPOSE: To evaluate the clinical results of treating nonrestorable teeth with
      conjunctive efforts of orthodontic-prosthodontic disciplines and periodontal
      therapy. METHODS: 10 cases, 8 anterior teeth, 2 premolar were selected, with a
      large vertical root fracture lingually or labially extending 2 to 3 mm below the
      gingival margin. The teeth were erupted coronally by orthodontic forces, and
      stabilized by the appliances for 8 weeks to 6 months, then periodontal surgery
      was performed, at last the final restoration was completed. RESULTS: After a
      series of treatments, an acceptable restoration was fabricated which fit the
      periodontal,restorative and esthetic requirements. Radiographs showed suitable
      C/R (crown and root) ratio of the final restoration. CONCLUSION: Forced eruption
      may be a useful approach in treating isolated nonrestorable teeth.

PMID- 15995766
TI  - [IRF6 gene mutation analysis in a van Der Woude syndrome family in Henan
      province].
AB  - PURPOSE: To investigate IRF6 gene mutation in a van Der Woude syndrome (VWS)
      family in Henan province. METHODS: PCR and DNA sequencing was employed to detect
      the mutation of IRF6.Secondary construction transformation analysis was performed
      using PIX-Protein Identification software. RESULTS: A CGC>TGC(r.279c-->t)
      transversion of IRF6 was identified in condon 6, showing complete segregation
      with the disease phenotypes and was resulting in changes of the secondary
      constructure of IRF6. CONCLUSION: VWS is caused by mutations in IRF6 gene, and
      IRF6 is closely related to the development of lip, palate and tooth.

PMID- 15995767
TI  - [Longitudinal study of the stability and reproducibility of natural head position
      in adolescents with different facial types over time].
AB  - PURPOSE: The aim of this study was to investigate the stability and
      reproducibility of natural head position (NHP) in adolescents with three
      different facial types. METHODS: The material consisted of intact lateral
      cephalograms of 30 male subjects and 30 female subjects, taken at 6, 9, 12, 15,
      18 years in NHP. These subjects were selected randomly and divided into three
      groups based on the MP-SN angle at approximately 15 years of age. Serial
      cephalometric roentgenograms traced upon the superimposition method based on the
      "best fit" of anterior cranial base structures. The changes of NSL/VER angulation
      were analyzed statistically. RESULTS: The standard deviation of the NSL/VER
      angulation at 6 year occasion, the mean incremental values, the standard
      deviation and the method error of NSL/VER angulation during the period from 6
      years occasion to any other occasion were larger, the coefficient of reliability
      was much more lower than the others. The standard deviation and the mean
      incremental values among 9-year, 12-year, 15-year and 18-year occasions were
      lower. The coefficient of reliability range from 76% to 97% and the method error
      at these six periods ranged from 1.84 degrees to 3.48 degrees in three facial
      types. There was different natural head position in three different facial types
      with cross-sectional comparison. The angulation in LFT was significantly larger
      than AFT and HFT, and the values in HFT were the smallest. However, there were no
      significantly statistical differences in three facial types as the change
      magnitude of NHP over time was compared. CONCLUSIONS: These suggest that the NHP
      of children at 6 years occasion or during the period from 6 years to 9 years of
      age is highly variable and this situation should be paid attention on while the
      facial growth studies and the cephalometric radiogram are made. The variance of
      NHP during any periods from 9 years to 18 years of age in three facial types (3.4
      degrees to 12.1 degrees ) is much more less than the variance of intracranial
      reference planes to the vertical (25 degrees to 36 degrees ). Cephalometric
      analyses upon NHP in different facial types among these four occasional
      radiograms are rather highly valid. Supported by Research Fund (No.300411) from
      Zhejiang Province.

PMID- 15995768
TI  - [A study on the extraoral cervical traction in the treatment of skeletal Class II
      division 1 malocclusion in mixed dentition].
AB  - PURPOSE: To evaluate the effects of extraoral cervical traction on skeletal Class
      II division 1 malocclusion of early or late mixed dentition and discuss the
      optimal treatment timing. METHODS: The sample consisted of two groups of skeletal
      Class II division 1 malocclusion. One group with 11 cases was treated started in
      early mixed dentition while the other with 15 cases in late mixed dentition. All
      cases were treated with extraoral cervical traction headgear. Cephalometric
      analysis was conducted to evaluate the treatment effects. Student's t test was
      applied for statistical analysis. RESULTS: SNA, ANB and the length of maxilla (A
      Ptm) were reduced and the inclination of maxillary incisor was decreased in both
      two groups. When comparing the two groups, it was found that the reduction of SNA
      was more notable, which means the inhibition of the maxilla was more evident in
      late mixed dentition. The difference was statistically significant (P<0.01).
      There was no significant difference on the distalization of the first upper molar
      between two groups (P<0.01). CONCLUSIONS: The extraoral cervical traction might
      be more effective in late mixed dentition to restrain maxillary growth in the
      treatment of skeletal Class II division 1 malocclusion.

PMID- 15995769
TI  - [CT analysis of 69 patients with nasopharyngeal carcinoma invading the Cranio
      maxillofacial structures].
AB  - PURPOSE: To analyze the characteristics of involvement of surrounding tissues in
      nasopharyngeal carcinoma(NPC). METHODS: CT images of 69 cases with
      preradiotherapeutic nasopharyngeal carcinoma were analyzed to calculate the rates
      of anterior spread(including pterygoid plates,pterygopalatine fossa, maxillary
      sinus, ethmoidal sinus, nasal cavity), lateral spread(including palatal muscle,
      parapharyngeal space, carotid sheath and infratemporal fossa), medial
      spread(including pharyngeal cavity, the contralateral side of the nasopharynx),
      posterior spread(including prevertebral muscle, cervical vertebra and clivus),
      superior spread(including sphenoidal sinus,foramen lacerum, foramen ovale,
      greater wing of sphenoid bone, petrous apex and intracranial region), inferior
      spread(including oropharynx, parapharyngeal space, soft palate, hard palate)
      respectively. RESULTS: 18 cases of in this series had anterior spread(26.1%); 53
      had lateral spread(76.8%); 31 had medial spread(44.9%); 32 had posterior
      spread(46.4%); 14 had superior spread(20.3%); 29 had inferior spread(42.0%).
      CONCLUSIONS: Lateral spread is the most common spread direction in nasopharyngeal
      carcinoma, followed by posterior spread, median spread, inferior spread, anterior
      spread, superior spread in turn.

PMID- 15995770
TI  - [Treatment of condylar fracture by external pterygoid muscle-condyle anatomical
      reduction and internal rigid fixation with mini titanium plates].
AB  - PURPOSE: To investigate the surgical indications, procedures and treatment
      outcomes of condylar fracture by external pterygoid muscle-condyle anatomical
      reduction and internal rigid fixation with mini titanium plates. METHODS:
      Patients with dislocation of the condylar head, fracture of the condylar neck and
      subcondylar neck (the degree of displacement greater than 30 to 45) and decreased
      vertical height of the ramus (greater than 4 to 5mm) were included in the study.
      Modified aural-temporal stick-shaped incision or retromandibular approach was
      adopted in 23 cases with 28 condylar fractures. The fractures were treated by
      external pterygoid muscle-condyle anatomical reduction and internal rigid
      fixation with mini tension band titanium plates. All the patients were re
      examined and evaluated 3 to 6 months after surgery in respects of facial
      symmetry, mouth opening, types of mouth opening, occlusion and mastication.
      RESULTS: All the patients had symmetrical face, mouth opening increased from
      26.7+/-7.2 (before surgery) to 38.4+/-5.6 (3 months after surgery) and 37.2+/-4.5
      mm(6 months after surgery). 2 patients with postoperative malocclusion had
      intermaxillary distraction for 1 week and their occlusion returned to normal.
      Radiographic check-up showed the condyle and titanium plates without
      displacement. No absorption was noted on the condylar surface. The patients had
      normal mastication. 2 patients with temporal facial paralysis recovered 3 months
      after conservative therapy. CONCLUSION: Treatment of condylar fracture by
      external pterygoid muscle-condyle anatomical reduction and internal rigid
      fixation with mini titanium plates in selected patients is an effective procedure
      for recovery of anatomical positions and masticatory function. Supported by
      Research Fund from Science and Technology Bureau of Jining city.

PMID- 15995771
TI  - [Analysis of the causes and emergency management of 154 traumatized permanent
      incisors in primary school children].
AB  - PURPOSE: This study was designed to investigate the related factors of permanent
      incisors trauma among primary school children, and evaluate the results of
      replantation of 56 avulsed teeth. METHODS: Data were collected by 122
      questionnaire from teachers or parents of the primary school children with dental
      trauma, with regard to the related trauma causes, altitudes and emergency
      management of dental avulsion. 56 avulsed teeth were replanted immediately after
      appropriate manipulation. The results of replantation were evaluated 1 year
      later. RESULTS: Tumble (fall off) was the main cause for dental trauma. The
      maxillary central incisor was most vulnerable to injury, without differences
      between the right and the left side. Single tooth injury was predominant in all
      age groups. Children with an incisal overjet tended to have a greater chance of
      dental trauma. Crown fractures represented 89 (57.79%)of 154 traumatized teeth;
      root fractures represented 9 (5.84%); avulsed represented 56 (36.3%). Most
      teachers and parents had little knowledge of the correct procedures for
      replanting or transporting avulsed teeth. 53 of 56 replanted teeth (94.64%) were
      integrated successfully. CONCLUSION: The parents and school educators should be
      advised about prevention of injuries and actions to be taken in case of an
      accident. The functional and esthetical outcome of replantation in avulsed teeth
      is excellent.

PMID- 15995772
TI  - [A clinical study of Periocline on the treatment of severe chronic
      periodontitis].
AB  - PURPOSE: To evaluate the clinical effect of subgingivally administering
      Periocline as an auxiliary treatment of chronic periodontitis. METHODS: A
      randomized, single-blind, self-control study was designed.Following initial
      therapy ,Periocline was administered into the periodontal pocket of treatment
      sides at baseline and week 1 to week 4, but the control sides received no drug.
      For both groups,standard clinical indices including plaque index (PLI), gingival
      index(GI), probing depth (PD) and response to the ointments were evaluated at
      baseline week 1,week 4 and week 8. The plaque index and gingival index were
      analyzed by Wilcoxon' test for each treatment. The probing depth was analyzed by
      Student's t test. RESULTS: At the baseline,there was no significant difference in
      the indexes between the two groups (P>0.05). At 1 week after treatment, both
      groups showed significant improvement in their examined indexes (P<0.01). At week
      1 the PLI was significantly lower in the experimental group than that in the
      control group; at week 4 and week 8 there was no significant difference between
      the groups. At 1 week after the treatment, the GI had no significant difference
      between the two groups (P>0.05); but there was difference 4 weeks and 8 weeks
      after treatment. At 1 week after treatment, PD was significantly different
      between the two groups (P<0.05), while at week 4 and week 8, were significant
      difference between the two groups (P<0.01). CONCLUSION: Administration of the
      local drug delivery system of Periocline ointment as the auxiliary treatment of
      severe chronic Periodontitis could get good clinical results.

PMID- 15995773
TI  - [Ectopic osteogenic ability of BMSCs on various scaffold materials in nude mice].
AB  - PURPOSE: To explore the ectopic osteogenic abilities of bone marrow stromal cells
      (BMSCs) on different scaffold materials in nude mice. METHODS: Canine BMSCs in
      vitro cultured were seeded at the density of 1x10(6)cells/cm(2) onto scaffolds of
      freeze-dried demineralized bone matrix (fdDBM), tricalcium phosphate (TCP),
      200microm coralline hydroxyapatite (CH200) and 500microm coralline hydroxyapatite
      (CH500). The cell adherence and growth on the materials were examined by SEM and
      H&E staining after 4 to 7 days of in vitro culturing. To observe the ectopic
      osteogenic capacity, four 10mmx5mmx2mm cell/scaffold complexes (fdDBM, TCP,
      CH200, CH500) and a blank control scaffold (fdDBM only) were implanted
      subcutaneously into each of athymic mice (n=8). The implants were harvested after
      9 weeks and H&E stained. Newly formed trabecular bone volume (TBV) was measured
      by IMAGER-PRO PLUS software, and statistical analysis was performed by ANOVA with
      SAS software. RESULTS: Canine BMSCs adhered to all 4 types of scaffolds and
      spread well in their pores 7-8 days after seeding. Athymic subcutaneous ectopic
      osteogenesis were observed in all the specimens of TCP, CH200, CH500 but were
      observed only in 75% of BMSCs/fdDBM and 25% of fdDBM. The TCP group showed
      significant higher TBV percentage (28.2%+/-2.86) than CH200 group (24.1%+/-4.12)
      and CH500 group (18.1%+/-4.66) (P<0.01). CONCLUSIONS: BMSCs adhered to all 4
      scaffolds. When combined with BMSCs, TCP exhibited the greatest osteogenic
      potential, which indicates that it might be an excellent scaffold material in the
      field of bone tissue engineering. Supported by National 973 Project (G1999054300)
      and National Natural Science Foundation of China(30271426).

PMID- 15995774
TI  - [Teniposide inducing apoptosis and G2/M phase arrest of Tca8113 cells].
AB  - PURPOSE: The present study is designed to identify quantitatively the in vitro
      effect of VM-26 against oral squamous cell carcinoma Tca8113 and to explore the
      underlying mechanism. METHODS: Human tongue squamous cell carcinoma cell line
      Tca8113 was used as subject. Cells were incubated with VM-26 of various
      concentrations for a variety of time spans. Cisplatin (CDDP) was employed as a
      control agent. MTT assay was used to assess the inhibition of cell growth by VM
      26. Flow cytometer (FCM), transmission electron microscope (TEM) and fluorescence
      staining were employed for determining the apoptotic rate of cells induced by VM
      26. Cell cycle distribution of Tca8113 cells incubated with VM-26 was examined
      through flow cytometer assay. SAS 6.12 was used for one-way ANOVA. RESULTS: The
      IC50 of VM-26 against Tca8113 cells was 0.35microg/ml and that of CDDP was
      1.1microg/ml. The changes in morphology and ultrastructure of Tca8113 cells were
      observed using fluorescence microscope and TEM, and apoptotic morphological
      feature could be found in the nucleus. Apoptotic rate of Tca8113 cells incubated
      with VM-26 of 5.0microg/ml for 72 hours was 81.01% and cell cycle appeared was
      arrested at S phase. However, exposed to VM-26 of 0.15microg/ml for 72 hours,
      Tca8113 cells in the G2/M phase increased from 12.75% to 98.71%, while the
      apoptotic rate of these cells was 17.38% and far below than that of cells treated
      with VM-26 of 5.0microg/ml. CONCLUSION: VM-26 could significantly induce
      apoptosis of oral squamous cell carcinoma cells and inhibit cell growth. There
      may be another pathway to induce apoptosis of oral squamous cell carcinoma cells
      except for G2/M phase arrest. Supported by National Natural Science Foundation of
      China (30300388, 30171014, 30330580) and Research Grant (No.036505013, 034107002)
      of Science and Technology Committee of Shanghai Municipality.

PMID- 15995775
TI  - [The construction of pSecTag2/B vector modified by osteoprotegerin].
AB  - PURPOSE: In order to treat periodontitis by using tissue engineering and gene
      engineering technology, we constructed mammalian secreted expression pSecTag2/B
      OPG vector, the cDNA sequence encoding osteoprotegerin(OPG) obtaining from 293
      cell. METHODS: The primers were designed based on the human OPG cDNA sequence.
      Total mRNA was isolated from 293 cells and RT-PCR was performed .The fragment was
      recombined into pSecTag2/B vector and sequenced by automatic sequence analyzer.
      RESULTS: The sequences of OPG cDNA from 293 cell by RT-PCR were completely
      identical to the sequences provided by GenBank [gi:33878056]. After polymerase
      chain reaction and the recombinant plasmid digesting with Hind III,EcoR I and
      BamH I,1% agarose electrophoresis showed several fragments, which were consistent
      with predicted size. CONCLUSION: From cultured 293 cells the cDNA has been cloned
      and pSecTag2/B-OPG vector has been constructed successfully. Supported by
      Research Fund (No.03043304) from Anhui Provincial Natural Science Foundation.

PMID- 15995776
TI  - [Histopathological study of the effects of intra-articular injection of
      triamcinolone acetonide on temporomandibular joint osteoarthrosis in goats].
AB  - PURPOSE: The aim of this study was to investigate the histopathological changes
      of human temporomandibular joint osteoarthrosis following intra-articular
      injection of triamcinolone acetonide, and compare the results to these of control
      group. METHODS: The upper compartments of both joints of 10 goats were injected
      with 0.8 ml collagenase I to induce osteoarthrosis. The 10 goats were then
      equally divided into control group and experimental group. The first and second
      treatment were carried out 30 and 60 days after injection of collagenase I,
      respectively. The animals were sacrificed 90 days after the first treatment. The
      specimens of the animal TMJ were harvested, histologically examined under light
      microscopy and scanning electron microscopy, and scored in a subjective manner
      following the criteria which was a modification of the method of Mankin et al and
      Yoshimi et al. GLM model in SAS software package was adopted to compare the
      differences between the control group and experimental group. RESULTS: Under
      light microscopy and scanning electron microscopy, the condyle, meniscus and
      glenoid fossa of the control group demonstrated distinct osteoarthrosis; the
      histopathologic changes in the experimental group was more serious than the
      control group, and the differences of the histologic scores were significant
      between the two groups (P<0.01). CONCLUSION: Intra-articular injection of
      triamcinolone acetonide as a lytic agent will worsen for articular cartilage
      reparation.

PMID- 15995777
TI  - [A three-dimensional finite element analysis for the biomechanical
      characteristics of orthodontic anchorage micro-implant].
AB  - PURPOSE: To establish a three-dimensional finite element model for orthodontic
      anchorage micro-implant,and to analyze the influence of different titled angles
      on the biomechanical characteristics of orthodontic anchorage implant-bone
      interface. METHODS: ANSYS(Analysis System)finite element analysis software was
      used to perform the finite element modeling of the micro-implant with 7 different
      tilted angles, including 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70
      degrees, 80 degrees and 90 degrees. A simulated orthodontic force, which was 200
      grams, was loaded mesiodistally to the mathematical models. The stress and
      displacement distribution on the implant-bone interface were analyzed. RESULTS:
      As the titled angle increased, the Von-Mises stress at the cervix of the implants
      were 1.0792, 1.0104, 0.8848, 0.8181, 0.7583, 0.6339 and 0.5608MPa, while the
      displacement were 5.5513, 4.9900, 3.7419, 3.1264, 2.5874, 1.3624 and 0.8027microm
      CONCLUSION: The micro-implant can be safely loaded with 200 grams of mesiodistal
      orthodontic force. The increase of the titled angle can efficaciously enhance the
      ability,implicating that the implant can bear a mesiodistal orthodontic force,
      vertical angle should be chosen when the micro-implant is embedded. Supported by
      Natural Science Foundation of Liaoning Province (20042076).

PMID- 15995778
TI  - [Study on the expression of IL-10 mRNA and the protein in gingival tissues of
      patients with chronic periodontitis].
AB  - PURPOSE: To investigate the cell type which express IL-10 mRNA and the protein in
      gingival tissues of patients with chronic periodontitis. METHODS: 12 patients
      with chronic periodontitis who were undergoing flap operation were randomly
      chosen as periodontitis group;10 patients undergoing gingivectomy were chosen as
      gingivitis group;6 patients undergoing extraction of impacted teeth were chosen
      as control group. Assays of in situ hybridization and immunohistochemistry were
      used to observe the expression of IL-10 mRNA and the protein in gingival tissues
      of each group respectively . Wilcoxon test was used to compare the expression of
      IL-10 of each group at two levels; differences between the two groups were
      analyzed by one-way ANOVA test. RESULTS: IL-10 mRNA and the protein were all
      expressed in gingival tissues of periodontium,they were found in lymphocytes,
      fibroblasts and macrophages. There were no significant differences between two
      levels of IL-10 expression of periodontitis group and control group (P>0.05)
      gingivitis group,P<0.05). The IL-10 expression of periodontitis group was
      significantly higher than gingivitis group and control group (P<0.01); The IL-10
      mRNA expression of periodontitis group was significantly higher than control
      group (P<0.01),but there was no significant difference between the IL-10 mRNA
      expression of periodontitis group and gingivitis group (P>0.05). CONCLUSION:
      There is a local secretion mechanism of IL-10 in the periodontal tissues.

PMID- 15995779
TI  - [Modulation of Chinese prescription Shenyang on Th1/Th2 cytokines in serum of SD
      rats with squamous cell carcinoma of the tongue].
AB  - PURPOSE: Prospective research demonstrated that Chinese prescription Shenyang
      could prolong the survival time and improve the survival rate of patients with
      oral squamous cell carcinoma (SCC). But the mechanism was not clear. The purpose
      of this study was to investigate effect of Shenyang on the level of Th1/Th2
      cytokines in serum of SD rats with SCC of tongue and clarify its mechanism.
      METHODS: Among 80 SD rats fed by 0.002% 4-nitroquinoline-1-oxide (4NQO) drinking
      water for 36 weeks, 61 with SCC of tongue had been found and randomly divided
      into 4 groups, namely Shenyang A, Shenyang B, positive and negative control
      group. Before and after high and low dosage of Shenyang, acanthopanax senticoside
      and water had been given for 15 days respectively, peripheral blood serum was
      collected. Secretion of Th1-type cytokines, such as IFN-gamma, IL-2, TNF-alpha
      and Th2-type cytokines, such as IL-4, IL-10 were detected by enzyme-linked
      immunosorbent assay (ELISA). Statistical analysis was made with paired t test.
      RESULTS: Shenyang significantly enhanced ,the serum levels of Th1-type cytokine,
      TNF-alpha and IL-2 (P<0.05), and decreased the expression of Th2-type cytokine,
      IL-4 and IL-10(P<0.05). Serum IFN-gamma had been increased to some extent.
      CONCLUSION: Reversing Th2 to Th1 cytokines and then enhancing the immunity may be
      one of the mechanisms in anti-tumor effect of Shenyang. Supported by Science and
      Technology Development Fund (No.014319359) of Shanghai Municipality.

PMID- 15995780
TI  - [Comparison of the effects of 5 irragant combinations on cleaning of anterior
      straight root canal walls].
AB  - PURPOSE: To evaluate the effect of 5 kinds of irrigant combinations on cleaning
      of anterior straight root canal walls. METHODS: 25 extracted human maxillary
      anterior teeth, with a single straight root were randomly divided into 5 groups.
      They were instrumented with K-files and conventional preparation technique. The
      irrigations were as follow: in group 1,the canals were irrigated with 1% NaOCl
      and 3% H2O2 in sequence during and after instrumentation.In group 2,the canals
      were irrigated with 1% NaOCl during instrumentation and after instrumentation
      being irrigated with 17% EDTA. In group 3,irrigation during and after
      instrumentation was accomplished using 17% EDTA and 1% NaOCl in sequence. In
      group 4,irrigation during instrumentation was accomplished using 17% EDTA and 1%
      NaOCl in sequence, and after instrumentation being irrigated with 17% EDTA.In
      group 5,the canals were irrigated with 17% EDTA, 1% Triton X-100 and 1% NaOCl in
      sequence during instrumentation and irrigated with 17% EDTA after
      instrumentation. The total amount of irrigant was 22ml and the irrigation time
      was 7 minutes in each root canal. The root was split longitudinally and 3
      specimens in each group were evaluated regarding to the smear layer, debris and
      erosion of dentinal tubules with SEM at the coronal, middle and apical thirds.
      RESULTS: In group 1, typical amorphous smear layer and abundance of debris were
      seen on the wall of canals. In group 2, the smear layer was removed partly in
      coronal and middle thirds, but the apical surface of the canal walls were covered
      with a typical amorphous smear layer. Although irrigants of group 3 could remove
      smear layer effectively, it resulted in moderate erosion of dentinal tubules. In
      group 5, part of the smear layer was removed on the surface of coronal and middle
      thirds but abundance of debris were present on the surface at the apical levels.
      Severe erosion was noted on the root canal surfaces in this group. Irrigation of
      group 4 had the best result: it not only removed smear layer effectively ,but
      also had no erosion on dentinal tubules. CONCLUSION: Using the combination of 17%
      EDTA and 1% NaOCl can remove smear layer effectively and has no erosion on the
      dentinal tubules under the condition of strict time control and irrigation
      sequence. Supported by Phosphor Plan (No.01QB14025) of Science and Technology of
      Shanghai Municipality.

PMID- 15995781
TI  - [Immunization with the fusion protein of GBD of Streptococcus mutans glucan
      binding protein-A against dental caries in SD rats].
AB  - PURPOSE: To observe the effect of immunization with the fusion protein of GBD of
      Streptococcus mutans glucan binding protein-A against dental caries. METHODS:
      Purified fusion protein of GBD of Streptococcus mutans glucan binding protein-A
      was used to immune SD rats by subcutaneous injection route. The rats were fed
      with Keyes Diet 2000 and infected by S.mutans. The caries level was determined
      and the result was analyzed by t test. RESULTS: The caries score of SD rats
      decreased in the group of immunized with GBD fusion protein,P<0.01. CONCLUSION:
      Immunization with GBD fusion protein resulted in significantly reduced dental
      caries after infection with S.mutans Ingbritt. Supported by PLA Tenth Five-Year
      Key Project (01Z089).

PMID- 15995782
TI  - [A primary construction of the 3D finite element model for fixed edgewise
      appliance].
AB  - PURPOSE: To construct a three-dimensional finite element model (3D-FEM) of the
      fixed appliance for mechanical analysis. METHODS: The figures of the brackets and
      the edgewise wire were constructed at the platform of powerSHAPE3040, based on a
      male's figures of mandibular dentition and alveolar bone. First, the bracket slot
      center plane (H plane) was lined, which was 4.3mm under the mesial buccal cusp of
      the 2nd molar and parallel to the XY plane. The point that each tooth's axis of
      buccal surface (line A) crossed the H plane was at the bracket's center (point
      O). Second, on the basis of H plane, line A, and point O, 0.018 inchx0.025 inch
      brackets were constructed on the teeth. All the slots were on the H plane.Then,
      according to the brackets' slots, plane f was gotten, which went through every
      slot smoothly and was perpendicular to the XY plane. At the base of slots' basal
      wall and gingival wall, the 0.016 inchx0.022 inch wire was constructed on the
      plane f. The figures of edgewise wire, teeth, alveolar bone, and brackets were
      transferred to ANSYS5.5 system in the IGES format. The teeth, periodontal
      membrane (PDM), alveolar bone, and brackets were broken down to 4-node
      tetrahedron element. The 10-node tetrahedron element was chosen to make the model
      of edgewise wire. RESULTS: The 3D-FEM of the brackets with teeth, PDM, alveolar,
      and the edgewise wire about the mandible were obtained. This kind of bracket was
      torqued slot bracket, which is similar to the preadjusted appliance. The edgewise
      wire was not as same as catenary curve or parabola completely. There were inset
      and offset on the wire following the dentition model. When the plain edgewise
      wire was inserted in the brackets, there was no force between the wire and
      brackets. If the wire was deformed as designed, the action could be analyzed.
      CONCLUSION: 3D mechanical analysis about the fixed appliance could be done on the
      model.

PMID- 15995783
TI  - [How to use free-text terms and subject headings for medical literature search].
AB  - This paper provides a description of the methods, skills, and knowledge of expert
      searchers working on medical literature search. Searching is a critical part of
      scientific research, as errors made in the search process potentially result in a
      biased or otherwise incomplete evidence base for the research.We hope that this
      paper will be helpful and lead the reader to develop a more systematic approach
      to literature searching.

PMID- 15995784
TI  - Molecular biology and its applications in orthodontics and oral and maxillofacial
      surgery.
AB  - Molecular biology is an exciting, rapidly expanding field, which has enabled
      enormously greater understanding of the biology of diseases and malfunctions in
      many fields. It chiefly concerns itself with understanding the interactions
      between the various systems of a cell, including the interrelationship of DNA,
      RNA and protein synthesis and how these interactions are regulated. Since the
      introduction of molecular biology into modern science, numerous other fields have
      been enabled to go "molecular". Advanced molecular biological techniques showed
      us new avenue towards finding answers to the questions asked for decades. The
      first part of this article described the history of molecular biology. It started
      as a joined discipline of other areas of biology, i.e. genetics and biochemistry
      in the 1930s and 1940s, and enjoyed its classical period and became
      institutionalized in the 1950s and 1960s. Major molecular techniques manipulating
      proteins, DNA and RNA were introduced and their mechanisms were concisely
      illustrated. The current knowledge of molecular biology and their applications in
      orthodontic and oral and maxillofacial surgery, i.e. osteoclast differentiation
      and function, regulation of tooth movement, mechanotransduction/cell-signalling,
      bone fracture healing, oral cancer as well as craniofacial/dental anomalies and
      distraction osteogenesis were discussed. Although the problems of introducing
      molecular technologies are still substantial, it is anticipated that the future
      of medicine/dentistry will be "molecular": molecular prevention, molecular
      diagnosis and molecular therapy.

PMID- 15995785
TI  - [Extraction of 56 horizontally impacted teeth using dental implanter].
AB  - 50 cases, totally 56 horizontally impacted teeth were extracted using dental
      implanter to remove the alveolar bone. Another 56 horizontally impacted teeth
      were extracted using high speed turbine.It's concluded that is a safe and easy
      way using the dental implanter to remove the horizontally impacted teeth, and the
      reaction and the complications could be minimized.

PMID- 15995786
TI  - [The use of intermaxillary fixation screws in the management of jaw fractures].
AB  - 48 patients with fractures of the jaw bones were included in this study.
      Intermaxillary fixation screws were used for tractions between the upper and
      lower jaw and to regain occlusion relationship, followed by internal rigid
      fixation. Two days after reduction of the fractures, intermaxillary tractions
      were carried out and the fixation screws remained for 2 weeks. All the wounds
      healed primarily with good occlusion. The wounds for screw placement healed well
      3 to 5 days after removal of the screws. Excellent occlusion recovered in 45
      patients, while in 3 patients, mild open bite developed which returned to normal
      after 2 weeks of intermaxillary tractions. It is concluded that intermaxillary
      fixation screws are time saving and efficient in the management of jaw fractures.

PMID- 15995787
TI  - [The effects of occlusal adjustment on retention of dental wedge-shaped defect].
AB  - To observe the retention of filling material for dental wedge-shaped defects
      after occlusal adjustment, patients in the experimental group was given suitable
      occlusal adjustment before filling with glass ionomer cements or light-curing
      composite resin according to the patient's requirements. Evaluation was carried
      out by statistical analysis after one year. The results showed significant
      difference in the retention between the experimental group and the control group
      (P<0.01) after one year. It's concluded that suitable occlusal adjustment of the
      teeth with wedge-shaped defect is beneficial to the retention of filling
      material.

PMID- 15995788
TI  - Remarks on surgical strategy in creating vascular access for hemodialysis: 18
      years of one center's experience.
AB  - The aim of the study is to evaluate surgical methods for creating vascular access
      for hemodialysis (HD) in patients with chronic renal failure. Over the last 18
      years, 1,827 surgical procedures were performed in 722 patients (399 men and 323
      women, mean age 43.7 +/- 17 years) in order to provide and maintain permanent
      vascular access for HD. Among all the surgical procedures, 992 were based on the
      construction of arteriovenous fistulas (AVF) and 835 were undertaken as secondary
      reparative surgical procedures. A total of 992 vascular accesses have been
      performed, including 904 AVF on upper and 14 on lower extremities as well as
      insertion of 74 permanent catheters. Radiocephalic AVF (RCAVF) was the principal
      type of AVF (58.8%). While constructing secondary angio-access after using RCAVF
      on the other extremity, fistulas with usage of brachial vessels were preferred. A
      total of 228 AVF of this type were created, including 143 brachiocephalic (BCAVF)
      and 85 brachiobasilic (BBAVF) AVF. Lately, synthetic grafts (arteriovenous graft,
      AVG) have been used more frequently, in 90 AVF. A brachial straight graft was the
      main type procedure performed, with polytetrafluoroethylene (95.6%). The patency
      of the fistulas has been evaluated. Kaplan-Meier survival curves were calculated
      to determine primary, primary-assisted, and secondary patency. Log-rank analysis
      was used to determine differences between curves. Primary, primary-assisted, and
      secondary patency at 12 months and 24 months were calculated. Comparing AVF
      patency in two patients' age periods (18-65 years, >65 years), it may be
      concluded that in the elderly group AVG provides better treatment for AVF.
      Finally, we conclude that a multidisciplinary approach to vascular access
      strategy offers the best option to achieve good functional AVF. Autogenous
      arteriovenous access should be regarded as the most suitable type in creating VA.
      However, individual conditions should be taken into consideration.

PMID- 15995789
TI  - On the effect of an applied magnetic field on the shear-induced pattern formation
      in nematic polymer liquid crystals.
AB  - The effect of an applied magnetic field and of the boundaries on the stability of
      the shear flow of nematic polymer liquid crystals of the tumbling type with
      respect to the formation of the transient spatially periodic patterns that
      appears after the start-up of shearing is studied. The unidirectional shear of a
      nematic director initially uniformly oriented orthogonally to the sample plane
      and with strong anchoring is considered. The magnetic field is applied
      orthogonally to the sample plane or in the same direction of the flow. For a
      given value of the Ericksen number of the flow a critical value of the magnetic
      to-viscous energy ratio shows up above which the uniform flow is stable. When the
      influence of the boundaries may be neglected, an internal Ericksen number that
      stays constant in a given material is considered such that the wavelength of the
      periodic pattern is a self-adjusted length. An internal generalized Ericksen
      number is defined such that it is a universal function of the magnetic-to-viscous
      energy ratio.

PMID- 15995790
TI  - Risk factors for painful bladder syndrome in women seeking gynecologic care.
AB  - The aim of this cross-sectional study was to report risk factors for painful
      bladder syndrome in women. We surveyed 645 women presenting for care to general
      gynecology clinics and a vulvar specialty clinic using a standardized
      questionnaire and validated outcome measures. We used two definitions for painful
      bladder syndrome, based on the O'Leary-Sant interstitial cystitis symptom and
      problem indices. Of those women surveyed, 29.5% met broader criteria and 8.5% met
      more restrictive criteria for painful bladder syndrome. After adjusting for
      confounders, bladder pain was significantly associated with current smoking,
      irritable bowel syndrome, and a generalized pain disorder. Tobacco use, the only
      modifiable association noted on multivariate analysis, has not been previously
      identified to our knowledge.

PMID- 15995791
TI  - What is the pain of interstitial cystitis like?
AB  - To describe the characteristics of pain experienced by patients with interstitial
      cystitis (IC) in terms of pain site, severity, and character, we performed a
      secondary analysis of data from the IC database (ICDB), which was a prospective,
      longitudinal, cohort study of IC patients. We analyzed the cross-sectional
      baseline data from 629 patients who had a completed baseline symptom
      questionnaire. Patients answered questions about whether they had pain or
      discomfort associated with urinary symptoms over the past 4 weeks and if so,
      about the location, characteristics, intensity, and frequency of their pain.
      Logistic regression examined associations between pain location and the presence
      of urinary symptoms. Analyses were performed using SAS version 8.2 (SAS
      Institute, Cary, NC, USA) and considered significant at the 5% level. Five
      hundred and eighty-nine (94%) patients with a mean age of 45 years (SD 14 years)
      reported baseline pain or discomfort associated with their urinary symptoms. The
      most common baseline pain site was lower abdominal (80%), with urethral (74%) and
      low back pain (65%) also commonly reported. The majority of patients described
      their pain as intermittent, regardless of the pain site. Most patients reported
      moderate pain intensity, across all pain sites. There was a statistically
      significant link between pain in the urethra, lower back, and lower abdomen, and
      urinary symptoms. Patients with IC report pain at several sites other than the
      bladder, possibly arising from the previously well-described myofascial
      abnormalities of pelvic floor and abdominal wall present in patients with IC and
      other chronic pelvic pain syndromes.

PMID- 15995792
TI  - In vivo comparison of suburethral sling materials.
AB  - In vivo tissue responses were compared for three commercially available
      polypropylene suburethral slings that differ markedly in fabric structure and in
      size of resulting interstices and pores. All three elicited the same basic
      inflammatory response; however, individual fabric structures produced distinct
      differences in tissue formation within each mesh. The presence of numerous,
      closely spaced, small diameter filaments prevented formation of extensive fibrous
      connective tissue within two slings (ObTape and IVS Tunneller mesh). The much
      larger diameter monofilament and open knit structure of the Monarc sling
      permitted the most extensive fibrous tissue integration. These differences may be
      of interest to physicians considering clinical use.

PMID- 15995793
TI  - Sarcopenia in premenopausal and postmenopausal women with osteopenia,
      osteoporosis and normal bone mineral density.
AB  - Sarcopenia, the decline of muscle mass with age, causes impaired gait, disability
      and falls. It may therefore increase the risk of fracture for osteoporotic women.
      The aims of this study were to determine the prevalence of sarcopenia in
      osteopenic and osteoporotic women, and to determine if hormone replacement
      therapy (HRT), diet, or physical activity (PA) has a role in the prevention of
      sarcopenia. One hundred and thirty-one premenopausal and 82 postmenopausal (54
      taking HRT) healthy women (17-77 years) volunteered for the study. Body
      composition was measured by dual X-ray absorptiometry (DXA). Sarcopenia was
      defined as a relative skeletal muscle index (RSMI) (appendicular skeletal muscle
      mass divided by height) below 5.45 kg/m2. Osteopenia was defined by a
      densitometric t-score for bone mineral density (BMD) (g/cm2) below -1.0 and
      osteoporosis by a t-score below -2.5. Nutrient intake was assessed using 3-day
      food records and physical activity (PA) was measured using the Baecke Physical
      Activity Questionnaire. Pearson chi-squared, independent t-tests, simple
      correlation and multiple regression were used to analyze the data. In
      premenopausal osteopenic women the prevalence of sarcopenia was 12.5%. In
      postmenopausal women it was 25% for those with osteopenia, and 50% for those with
      osteoporosis. PA was independently related to RSMI (beta=0.222, p=0.0001), but
      diet and HRT were not. After adjusting for PA, RSMI was not significantly related
      to BMD. These data suggest that the relationship between RSMI, BMD and risk of
      osteoporosis may largely be mediated through participation in PA. Sarcopenia
      screening simultaneous to BMD examinations by DXA, may be of value in identifying
      osteoporotic women with sarcopenia, a group that may be most in need of exercise
      interventions to increase muscle and BMD.

PMID- 15995794
TI  - Cevimeline hydrochloride improved cholinergic dysfunction in a patient with pure
      autonomic failure.

PMID- 15995795
TI  - Longitudinal evaluation of cerebral morphological changes in Parkinson's disease
      with and without dementia.
AB  - OBJECTIVE: To investigate the pattern of brain atrophy across time in a sample of
      Parkinson's disease (PD) patients with and without dementia using voxelbased
      morphometry (VBM) analysis. METHODS: The initial sample comprised thirteen non
      demented PD patients and sixteen demented patients. Longitudinal cognitive
      assessment and structural MRI were performed. The mean follow-up period was 25
      months (SD=5.2). From this initial group, eight PD patients with dementia (5 men
      and 3 women) and eleven PD patients without dementia (7 men and 4 women) were
      reevaluated. MRI 3D structural images were acquired and analyzed by means of the
      optimized VBM procedure with Statistical Parametric Mapping (SPM2). RESULTS: VBM
      analysis showed a progressive grey matter volume decrease in patients with PD
      without dementia in limbic, paralimbic and neocortical associative
      temporooccipital regions. In patients with dementia the loss mainly involved
      neocortical regions. CONCLUSION: VBM revealed a significant loss of grey matter
      volume in PD patients with and without dementia with disease progression. The
      decrease in limbic and paralimbic regions is widespread in non-demented patients.
      Neocortical volume reduction is the most relevant finding in patients with
      dementia. This suggests that the neocortex is a substrate for dementia in
      Parkinson disease.

PMID- 15995796
TI  - Characterization of tremor in phenylketonuric patients.
AB  - Tremor of unknown origin is detected in 10-30% of early-treated and in more than
      30% late-treated phenylketonuric patients. With the aim of characterizing tremor
      in phenylketonuria, we carried out a systematic study in 54 patients aged 6 to 37
      years. Tremor examination was done by applying the WHIGET Tremor Rating Scale and
      by accelerometer recording (BYOPAC System MP100WSW). Age at diet onset, IQ test
      results, concomitant plasma phenylalanine levels and index of dietary control
      were also studied. Tremor was not observed at rest in any case, but was apparent
      in 22 patients (40.7%) when carrying out a kinetic task. In 15 patients tremor
      was also evident during maintenance of a postural task at a frequency ranging
      between 7.5 and 12.7 Hz. Frequency of tremor was not significantly modified by
      loading the arms or by increasing muscle contraction. Patients with tremor had a
      later age at onset of phenylalanine restricted diet (p < 0.001). Other treatment
      related variables did not differ between patients with and without tremor. Our
      results of the neurophysiological examination suggest that tremor in
      phenylketonuric patients is dependent on a dysfunction of central nervous system
      networks and may be an index of cerebral damage.

PMID- 15995797
TI  - Amyotrophic lateral sclerosis, rural environment and agricultural work in the
      Local Health District of Ferrara, Italy, in the years 1964-1998.
AB  - Previous epidemiological surveys, both analytic and descriptive, in the Local
      Health District (LHD) of Ferrara, northern Italy, have indicated that rural
      residence and agricultural work might constitute risk factors for Amyotrophic
      Lateral Sclerosis (ALS). The present investigation is a demographic survey in the
      LHD of Ferrara in the years 1964-1998 which aimed to verify whether the level of
      urbanization and agricultural activities might influence the risk of ALS. Based
      on the data obtained in a recent incidence study in the LHD of Ferrara which
      reported a mean annual crude incidence rate of ALS in the years 1964-1998 of 1.63
      per 100,000 population (95 % CI 1.31-2.00), it was possible to compare the number
      of observed ALS cases and the number of expected ALS cases according to the level
      of urbanization and usual occupation on the basis of the residential and
      occupational pattern identified in the population of the LHD of Ferrara in the
      study period under the assumption of a homogeneous distribution of ALS. The
      present survey identified four different levels of urbanization in the LHD of
      Ferrara in the study period and for none of them was a difference between the
      number of observed and expected ALS cases found. Also in the most rural of the
      four identified levels of urbanization (small villages with an average population
      in the study period lower than 1,000 inhabitants and scattered houses in the
      countryside) no difference was found between observed and expected number of ALS
      cases (observed ALS cases 16, 95% Poisson CI 9.1-25.9, expected ALS cases 18.3).
      Based on the occupational pattern identified in the population of the LHD of
      Ferrara in the study period the number of incident cases of ALS whose usual
      occupation was in agricultural work exceeded the expected number (observed ALS
      cases 22, 95% Poisson CI 13.8-32.3, expected ALS cases 6.0). The present findings
      indicate that rural residence itself does not influence the risk of ALS while
      agricultural activities could influence the risk of ALS, with occupational
      exposure to agricultural chemicals playing a possible role.

PMID- 15995798
TI  - Gender differences in bipolar-II disorder.
AB  - Gender differences in bipolar-II disorder (BP-II) are understudied. STUDY AIM:
      was to test if there were gender differences in the clinical and family history
      features of BP-II. METHODS: Consecutive 374 BP-II private practice outpatients
      were interviewed by a senior psychiatrist using the Structured Clinical Interview
      for DSM-IV, modified to improve the detection of BP-II (by Benazzi and Akiskal
      2003, J Affect Disord 73:33-38), the Montgomery Asberg Depression Rating Scale
      (MADRS), the Hypomania Interview Guide, and the Family History Screen. Logistic
      regression was used to study associations and control for confounding. Alpha
      level was set at 0.05; P was two-tailed. RESULTS: Females represented 67.3% of
      the group. The female to male ratio was independent of age. Females were more
      common in younger onset BP-II. Females, versus males, had significantly lower age
      at onset, more axis I comorbidity, atypical depressions, intra-depression
      hypomanic symptoms (i. e., mixed depression), and family history of suicidal
      behavior. On the MADRS, females had more sadness, loss of energy, loss of
      interest, and suicidal ideas. The symptom structure of hypomanic episodes was
      similar between females and males. LIMITATIONS: Single interviewer, outpatient
      sample, private practice study setting. DISCUSSION: Clinical differences were
      found between BP-II females and males. Differences were found only on the
      depressive pole of the disorder. However, the magnitude of the differences had
      not a strong clinical significance, suggesting that at present, on the basis of
      the variables and the population studied, there is little ground to support a
      female BP-II depression.

PMID- 15995800
TI  - Social networks and community prevention coalitions.
AB  - This study investigates the links between community readiness and the social
      networks among participants in Communities That Care (CTC), community-based
      prevention coalitions. The coalitions targeted adolescent behavior problems
      through community risk factor assessments, prioritization of risk factors, and
      selection/implementation of corresponding evidence-based family, school, and
      community programs. Key leaders (n = 219) in 23 new CTC sites completed
      questionnaires focusing on community readiness to implement CTC and the
      respondents' personal, work, and social organization links to other key leaders
      in the community. Outside technical assistants also completed ratings of each
      community's readiness and early CTC functioning. Measures of network
      cohesion/integration were positively associated with readiness, while
      centralization was negatively associated. These results suggest that non
      centralized networks in which ties between members are close and direct may be an
      indicator of community readiness. In addition, we found different associations
      between readiness and different domains of social relations. EDITORS' STRATEGIC
      IMPLICATIONS: The authors present the promising practice of using social network
      analysis to characterize the functioning of local prevention coalitions and their
      readiness to implement a community-based prevention initiative. Researchers and
      community planners will benefit from the lessons in this article, which
      capitalizes on a large sample and multiple informants. This work raises
      interesting questions about how to combine the promotion of coalition functioning
      while simultaneously encouraging diversity of coalition membership.

PMID- 15995801
TI  - Community and school drug prevention strategy prevalence: differential effects by
      setting and substance.
AB  - This study used key informant interviews and student survey data in 508 U.S.
      communities to examine relationships between the prevalence of community and non
      classroom-based school substance prevention strategies and teen substance use
      rates. After controlling for covariates, analyses indicated that: (1) adult
      supervised after-school activities were significantly related to lower past 30
      day cigarette smoking and both past 30-day alcohol use and binge drinking; (2)
      unsupervised after-school recreational facilities were significantly associated
      with both lower past 30-day cigarette smoking and current daily smoking; (3)
      community activities to reduce substance use were significantly related to lower
      binge drinking; and (4) student organizations to prevent alcohol abuse were
      significantly related to lower binge drinking. Communities need a broad spectrum
      of strategies to address variation in substance use among youth. EDITORS'
      STRATEGIC IMPLICATIONS: Policymakers at the school, community, state, and federal
      levels will benefit from knowing that after-school activities for teens typically
      result in reliable (though often modest) reductions in substance use in this
      large national sample. This is a strategy that works, but the effects are likely
      to vary by setting, level of supervision, substance, and program implementation.

PMID- 15995802
TI  - Estimating intervention effectiveness: synthetic projection of field evaluation
      results.
AB  - In a 46-site, 5-year high-risk youth substance abuse prevention evaluation,
      effect sizes were adjusted using a meta-analytic regression technique to project
      potential effectiveness under more optimal research and implementation
      conditions. Adjusting effect size estimates to control for the impact of
      comparison group prevention exposure, service intensity, and coherent program
      implementation raised the mean effectiveness estimate from near zero (.02, SD =
      .21) to .24 (SD = .18). This finding suggests that adolescent prevention programs
      can have significant positive effects under optimal, yet obtainable conditions.
      EDITORS' STRATEGIC IMPLICATIONS: The authors present a meta-analytic technique
      that promises to be an important tool for understanding what works in multi-site
      community-based prevention settings. Researchers will find this to be a creative
      approach to model the "noise'' in implementation that may often overshadow the
      potential impact of prevention programs.

PMID- 15995803
TI  - Cost-effectiveness of a community-level HIV risk reduction intervention for women
      living in low-income housing developments.
AB  - We conducted a cost-effectiveness analysis of a multi-site community-level HIV
      prevention trial that enrolled women living in 18 low-income housing developments
      in 5 U.S. cities. A mathematical model of HIV transmission was used to estimate
      the number of HIV infections averted and quality-adjusted life years (QALYs)
      saved by the community-level intervention, based on data obtained from community
      wide sexual behavior surveys at baseline and 12-month follow-up. Results
      indicated that the intervention prevented approximately 1 infection per 3500
      women reached by the intervention, at a total cost of 174,845 dollars. The cost
      per QALY saved by the intervention was 37,433 dollars and the cost per HIV
      infection averted was 732,072 dollars. The community-level intervention was
      moderately cost-effective in comparison with other HIV prevention programs for at
      risk women. Synergistic approaches to HIV prevention that combine community-level
      sexual norm change interventions with more intensive risk reduction programs for
      high-risk women are needed. EDITORS' STRATEGIC IMPLICATIONS: The authors present
      a promising and efficient community-level HIV prevention approach, with effects
      beyond the limited scope of individual or small group interventions. This paper
      represents an example of how an analysis of cost-effectiveness can provide
      policymakers with information needed for difficult decisions about prevention
      resource allocations.

PMID- 15995804
TI  - Cigar smoking: an ignored public health threat.
AB  - Cigar smoking is rapidly increasing. Studies have exposed the move to cigar
      smoking by smokers who do not necessarily believe cigar smoking is risky
      behavior. However, cigar smoking poses significant risk that leads to well
      documented morbidity and mortality. Currently, there is a dearth of primary
      prevention efforts related to cigar smoking. Furthermore, the literature is
      lacking in program, practice, and theory development as well as in the planning,
      execution, and evaluation of programs targeting cigar smoking cessation. A clear
      need exists to promote early prevention of cigar smoking, and to incorporate
      cigar smoking cessation into other tobacco cessation projects.

PMID- 15995805
TI  - Mechanisms of liver regeneration and their clinical implications.
AB  - During the last few years there have been major advances in the understanding of
      the mechanisms of liver regeneration. These advances derived to a great extent
      from the increased use of transgenic and knockout mice. In parallel with the
      experimental work, human partial liver transplantation from cadavers and living
      donors continues to increase, stimulating hepatologists and surgeons to learn
      more about the mechanisms that regulate and promote regeneration. Thus, knowledge
      generated from laboratory work in rodents can be applied to clinical problems,
      while data on human transplantation can also guide the design of experimental
      work. In this review, we discuss a few selected aspects of liver regeneration
      that are of interest in both the laboratory and the clinic.

PMID- 15995806
TI  - Stem-cell therapy for hepatobiliary pancreatic disease.
AB  - The transplantation of pancreatic beta cells or hepatocytes represents a
      potential therapeutic approach for type I diabetes and inherited liver diseases,
      respectively. Furthermore, acquired liver diseases, particularly acute hepatic
      failure due to toxic or viral injury, have been treated in limited clinical
      trials with fetal and adult hepatocytes. However, a major limitation is the
      insufficient amount of beta cells and hepatocytes available for grafts.
      Alternative sources of these cells have yet to be determined. During the past few
      years, progress has been made in the development of new strategies to produce
      mature beta cells and hepatocytes. In this review, we outline the current state
      of scientific understanding and controversy regarding the properties of embryonic
      and adult stem cells in the field of hepatobiliary and pancreatic diseases. Our
      objective is to provide a framework of understanding for the challenges behind
      translating fundamental stem cell biology into clinical therapies.

PMID- 15995807
TI  - Hepatocyte differentiation from embryonic stem cells and umbilical cord blood
      cells.
AB  - With the development of regeneration medicine, many researchers have attempted
      hepatic differentiation from nonhepatic-origin cell sources. The differentiation
      of embryonic stem (ES) cells into hepatocyte-like cells has been reported in
      several papers. Mouse ES cells have shown a potential to develop into hepatocyte
      like cells in vitro on the basis of hepatic gene expression after adding several
      growth factors. We transplanted cultured embryoid body (EB) cells (male) into
      female mice. A liver specimen of the recipient was examined by
      immunohistochemical staining for albumin and fluorescence in situ hybridization
      for the Y chromosome after transplantation. Both Y chromosome- and albumin
      positive cells were recognized in the recipient female liver, and were considered
      to be hepatocyte-like cells derived from ES cells containing the Y chromosome.
      Many groups, including ourselves, have studied hepatocyte-like cell
      differentiation from umbilical cord blood cells (UBCs). We cultured nucleated
      cells isolated from UBCs. Using immunostaining, ALB-positive and CK-19-positive
      cells were recognized in the culture. Dual staining of ALB and CK-19 demonstrated
      that ALB was coexpressed with CK-19, suggesting the existence of hepatic
      progenitors. In this review, we consider recent studies of the differentiation of
      hepatocytes from nonhepatic origins, especially ES cells and umbilical cord
      blood.

PMID- 15995808
TI  - Lesson from the GFP/CCl4 model--translational research project: the development
      of cell therapy using autologous bone marrow cells in patients with liver
      cirrhosis.
AB  - The plasticity of bone marrow has been confirmed by the analysis of autopsy
      findings in female recipients of bone marrow cells transplanted from male donors.
      To establish new clinical cell therapies using autologous bone marrow cells for
      patients with liver failure, we developed a new in vivo model, the "green
      fluorescent protein (GFP)/carbon tetrachloride (CCl(4)) model". Using the
      GFP/CCl(4) model, we found that transplanted Liv8-negative cells efficiently
      repopulated into cirrhotic liver tissue and trans-differentiated into albumin
      producing hepatocytes under conditions of persistent liver damage induced by
      CCl(4). Moreover, one marrow cell transplantation into liver cirrhosis mice
      improved their liver function, ameliorated liver fibrosis, and improved their
      survival rate. Results from the GFP/CCl(4) model showed that cell therapy using
      autologous bone marrow cells has the potential to become an effective treatment
      for patients with liver failure. Here we describe the findings from the
      GFP/CCl(4) model and the scope of the translational research project.

PMID- 15995809
TI  - Pancreatic differentiation.
AB  - Over the last decade, with the advent of new techniques and technologies in
      modern molecular biology, our understanding of the underlying mechanisms
      responsible for organ differentiation has developed rapidly. Despite this, our
      knowledge of these signaling pathways is still far from complete. Some of these
      advances, such as the creation of transgenic mouse models, have given us new
      tools to help us understand the interactions of the various transcription factors
      that are responsible for the creation of various cell types from a single cell
      type during embryogenesis. This knowledge then gives rise to the concept of
      creating new ways to manipulate stem cells in order to correct the deficiencies
      present in various disease processes. Here, we present work that focuses
      specifically on pancreatic development. The ultimate goal of our research in
      studying the mechanisms of the basic differentiation of pancreatic precursor
      cells is to gain the knowledge necessary to be able to engineer stem cells
      specifically into beta-cells in the treatment of diabetes.

PMID- 15995810
TI  - Regenerative medicine of the pancreatic beta cells.
AB  - Diabetes mellitus is a metabolic disorder that affects millions of people. The
      number of patients suffering from diabetes continues to increase all over the
      world. Both type 1 and type 2 diabetes result from an inadequate mass of
      functioning beta cells. To achieve the ultimate goal of curing diabetes in the
      future, the mechanism of the regenerative process of the adult human pancreas
      must be elucidated. In this review, we first summarize the regenerative processes
      of the pancreas observed in animal models in vivo, and approaches to promote the
      regeneration of the pancreas in vivo. Next we consider other new approaches, such
      as stem cell research and cell-based therapy, for the cure of diabetes in the
      future. Based on the innovative success of the Edmonton protocol, islet
      transplantation has been considered to be a new therapeutic option for the
      treatment of diabetes. However, a serious shortage of donor pancreata is a
      critical problem. We suggest that the following issues should be solved in order
      to realize cell-based therapy. The first is to establish a source of
      stem/progenitor cells that will multiply easily in vitro and maintain their
      property as progenitor cells. The probable use of adult stem cells will
      circumvent potential ethical problems, and autotransplantation will become
      possible. The most difficult and as yet unsolved issue is how to differentiate
      these cells and acquire fully functional islets. Further investigations to
      understand the regenerative process of the adult pancreas and the appropriate
      induction of stem cell differentiation will help to establish cell-based therapy
      in diabetes.

PMID- 15995811
TI  - Pancreatic islet cell transplantation using non-heart-beating donors (NHBDs).
AB  - Recent dramatic improvements in clinical islet cell transplantation demonstrated
      by the Edmonton group have increased the demand for this treatment, and donor
      shortage could become a major problem. Utilization of marginal donors could
      alleviate the donor shortage, and non-heart-beating donors (NHBDs) might be good
      resources. The University of Pennsylvania group demonstrated that it was possible
      to isolate islets from NHBDs, and the group actually transplanted islets from
      NHBDs, for the first time. The patient became insulin-independent; however, there
      had been no more cases using NHBDs until our group initiated islet
      transplantations from NHBDs in Japan. In order to utilize NHBDs effectively, we
      modified the standard islet isolation method. These modifications included
      minimizing the warm ischemic time, the use of trypsin inhibition during
      isolation, carrying out density measurement before purification and the use of a
      less toxic islet purification solution. With these modifications we were able to
      transplant nine of ten islet preparations from ten NHBDs (90%), into five type-1
      diabetic patients. The first transplantation was performed on April 7, 2004 (the
      first time in Japan), and this patient became insulin-independent after the
      second islet transplantation (first time in Japan). All patients showed improved
      glycemic control and reduced insulin requirements, without hypoglycemic events.
      We also performed living-donor islet transplantation, with our modified islet
      isolation protocol, on January 19, 2005. The improved islet isolation protocol
      enabled us to perform effective islet transplantations from NHBDs, and it also
      enabled us to perform the living-donor islet transplantation.

PMID- 15995812
TI  - Reconstruction of the common bile duct by a vascular prosthetic graft: an
      experimental study in pigs.
AB  - BACKGROUND/PURPOSE: The purpose of the present study was to investigate whether
      it was possible to use a vascular graft for reconstruction of the common bile
      duct (CBD) in pigs. METHODS: Eight pigs, each weighing approximately 60 kg, were
      used for the experiments. The gallbladder was dissected and the cystic duct and
      cystic artery were ligated and divided. The CBD was displayed and divided. Then
      the CBD was reconstructed with a standard walled expanded polytetrafluoroethylene
      (ePTFE) vascular graft (internal diameter 4 mm) by means of 12 interrupted
      monofilament glycomer 63 (Biosyn) 4.0 sutures. The ends of the vascular graft
      were inserted into the CBD and the sutures were placed through the graft and the
      CBD in such a way that the latter would cover the former. The anastomotic line
      was covered by fibrin glue. On postoperative day 8, a laparotomy was performed;
      the pigs were investigated for signs of gall leakage, and cholangiography was
      performed. Blood samples for the determination of liver parameters were taken
      before the primary surgery and before the explorative laparotomy. RESULTS: At
      evaluations on the eighth postoperative day, all animals except one were without
      signs of bile leakage. One pig had an encapsulated biloma. Another animal had to
      be operated on day 6 because of illness, and laparotomy showed a perforated
      gastric ulcer, but no bile leakage. Cholangiography revealed slight intrahepatic
      dilatation in all animals. Bilirubin and alkaline phosphatase levels were
      unaffected by the surgery. CONCLUSIONS: Reconstruction of the CBD by means of a
      vascular graft seems to be a safe procedure in the short term in a pig model.

PMID- 15995813
TI  - Prophylactic hepatic irradiation following curative resection of pancreatic
      cancer.
AB  - BACKGROUND/PURPOSE: It is unlikely that adjuvant chemoradiotherapy applied to the
      pancreatic bed alone significantly improves the survival of patients with
      resectable pancreatic cancer. The aim of the present study was to determine
      whether prophylactic hepatic irradiation (PHI) improved patient outcome after the
      curative resection of pancreatic cancer. METHODS: The study population was
      comprised of 34 patients (PHI group) who were administered PHI after curative
      resection of pancreatic cancer between September 1994 and December 2003. The
      whole liver was irradiated with a total dose of 19.8-22.0 Gy under continuous
      infusion of 5-fluorouracil. The cumulative rate of liver metastasis and the
      survival outcomes of the PHI group were compared with those of 31 patients
      without PHI (non-PHI group) who underwent curative resection of pancreatic
      cancer. RESULTS: The planned PHI was completed for 32 of the 34 patients. Two
      patients developed complications that might have been PHI-related. One developed
      liver abscesses which were successfully managed by percutaneous drainage. The
      other died of liver failure without recurrence 11 months after the operation. The
      cumulative incidence of liver metastasis was significantly lower for the PHI
      group than the non-PHI group (P=0.0455). Patients in the PHI group also survived
      significantly longer compared to those in the non-PHI group (P=0.0002).
      CONCLUSIONS: The present findings suggest that PHI is well tolerated and is a
      potentially effective treatment strategy after curative resection of pancreatic
      cancer, thereby providing the basis for a randomized controlled trial.

PMID- 15995814
TI  - Laparoscopic treatment of recurrent pyogenic cholangitis.
AB  - BACKGROUND/PURPOSE: We reviewed the selective use of hand-assisted laparoscopic
      segmentectomy (HALS) and laparoscopic choledochoduodenostomy (LCD) in the
      management of recurrent pyogenic cholangitis (RPC). METHODS: We carried out a
      retrospective review of a prospectively maintained database of laparoscopic
      treatment of RPC during the period 1995 to 2004. The perioperative data were
      analyzed. RESULTS: There were 33 laparoscopic procedures performed in 30 patients
      with RPC during the period 1995--2004. There were 23 female and 7 male patients,
      with a mean age of 63.2+/-14.9 years (range, 29--92 years). All these patients
      had a history of repeated attacks of cholangitis, and multiple sessions of
      endoscopic lithotripsy or operative retrieval had previously been attempted. Of
      these 33 procedures, there were 23 LCDs and 10 HALS. Three patients underwent
      simultaneous LCD and HALS in the same operation. The mean operative time was
      172+/-63.5 min (range, 75--290 min) and there were three open conversions (10%),
      due to (1) intraoperative bleeding from the left hepatic vein, (2) lost broken
      tip of ultrasonic dissector, and (3) significant bleeding during choledochotomy,
      respectively. Average hospital stay was 11.4+/-11.1 days (range, 5--60 days).
      Eight complications (26.6%) were encountered, which included four bile leaks,
      three wound infections, and one intraabdominal collection. Complete stone
      clearance was achieved in all but 1 patient (rate, 96.6%), in whom the residual
      stones were extracted through a postoperative combined endoscopic and
      percutaneous approach. Long-term results were satisfactory, and only one stone
      recurrence was detected, upon a mean follow-up of 34.7 months (range, 1--107
      months). CONCLUSIONS: Both LCD and HALS are safe, feasible, and effective
      treatments for patients with RPC.

PMID- 15995815
TI  - Adjuvant arterial infusion chemotherapy after resection of hepatocellular
      carcinoma with portal thrombosis: a pilot study.
AB  - BACKGROUND/PURPOSE: The prognosis of hepatocellular carcinoma (HCC) with tumor
      thrombosis of the main trunk or major branches of the portal vein (mPVTT) is
      extremely poor, even if it is curatively resected. Uncontrollable multiple
      metastases to the residual liver are often observed within several months after
      the operation. We report here the results of a pilot study, showing the efficacy
      of adjuvant arterial infusion chemotherapy after the resection of HCC with mPVTT.
      METHODS: Twelve patients had curative resection of HCC with mPVTT. Six of the
      patients were treated by the arterial infusion of a chemotherapeutic agent via a
      subcutaneously implanted injection port after curative resection of HCC with
      mPVTT. The initial course consisted of the daily administration of cisplatin
      (CDDP) and continuous infusion of 5-fluorouracil (5-FU). This was followed by the
      weekly or biweekly administration of CDDP and subsequent infusion of 5-FU until
      the cumulative dose of 5-FU reached 15 g. RESULTS: The median overall survival
      time was 58.0 months with adjuvant chemotherapy and 8.0 months without adjuvant
      chemotherapy. The median disease-free interval was 15.0 months with adjuvant
      chemotherapy and 4.0 months without adjuvant chemotherapy. Adverse reactions were
      tolerable nausea and loss of appetite. CONCLUSIONS: This chemotherapeutic regimen
      achieved favorable results and may be useful as adjuvant chemotherapy in treating
      patients after curative resection of HCC with mPVTT.

PMID- 15995816
TI  - Clinicopathology of pancreaticobiliary maljunction: relationship between
      alterations in background biliary epithelium and neoplastic development.
AB  - BACKGROUND/PURPOSE: Between 1988 and 2003, 38 patients underwent biliary
      resection for pancreaticobiliary maljunction (PBM). We reviewed the
      histopathologic findings for the surgically resected specimens to compare the
      clinical and pathologic features and assess the relationship between changes in
      the background biliary epithelium and the development of neoplasms. METHODS:
      Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM,
      was classified into grades 0--III in the gallbladder and grades 0--II in the
      extrahepatic bile duct, according to the extent, and was assessed for links with
      tumors in the same specimens. RESULTS: The incidence of gallbladder carcinoma was
      13/21 in grades I--II, versus 0/16 in grade III, while the incidence of bile duct
      carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these
      incidences for patients below age 50 years and age 50 or older were 1/18 versus
      12/20, and 0/14 versus 6/17, respectively. CONCLUSIONS: PHP of the biliary
      epithelium in PBM patients is an important precursor lesion, especially for
      gallbladder cancer, and the risk becomes greater with age, regardless of the type
      of pancreatobiliary junction (PBJ) and its location in the biliary tract.

PMID- 15995817
TI  - Embryonal rhabdomyosarcoma of the common bile duct mimicking choledochal cyst.
AB  - Embryonal rhabdomyosarcoma of the common bile duct is a very rare malignancy of
      childhood. The radiological appearance of the lesion is similar to that of
      congenital choledochal cyst if there is no local invasion to the adjacent
      tissues. The authors present a case of embryonal rhabdomyosarcoma of the common
      bile duct which was considered to be a congenital choledochal cyst
      preoperatively, and they discuss this very rare childhood tumor, with a brief
      survey of the literature. In conclusion, it is important to know that this rare
      tumor can simulate congenital choledochal cyst; it should be considered in the
      differential diagnosis of obstructive jaundice in children.

PMID- 15995818
TI  - Ectopic hepatocellular carcinoma arising in the bile duct.
AB  - We report a case of ectopic hepatocellular carcinoma arising in the bile duct. A
      72-year-old woman was transferred to our hospital with fever, abdominal pain, and
      jaundice. Contrast-enhanced computed tomography revealed a round mass, measuring
      25 mm in diameter, in the bile duct. The mass was causing obstructive jaundice.
      Endoscopic retrograde cholangiography showed a 27 mm x 21-mm round defect in the
      superior bile duct. These findings led to a diagnosis of bile duct tumor, and the
      patient underwent extrahepatic bile duct resection and biliary reconstruction.
      Gross examination of the tumor showed a fibrous capsule and a stalk arising from
      the bile duct mucosa. The tumor was diagnosed histopathologically as well
      differentiated hepatocellular carcinoma arising in the bile duct.

PMID- 15995819
TI  - Biliary injury after laparoscopic cholecystectomy: end-to-end anastomosis covered
      with umbilical vein.
AB  - The management of biliary injuries after laparoscopic surgery presents a surgical
      challenge. We describe a promising method of biliary reconstruction with
      umbilical vein covering followed by end-to-end anastomosis. In the patient
      reported here, the umbilical vein was identified in the pedicled ligamentum
      teres, transected as if it were a sheet, and sutured, then covered ventrally to
      the anastomosed bile duct. This procedure may be a promising reinforcement of the
      reconstructed site which maintains the biliary integrity; however, it can be
      applied, only in selected situations.

PMID- 15995820
TI  - Left trisegmentectomy and combined resection of the inferior vena cava, without
      reconstruction, for giant cystadenocarcinoma of the liver.
AB  - A 54-year-old woman with giant liver cystadenocarcinoma underwent left
      trisegmentectomy with combined resection of the inferior vena cava (IVC) and the
      right hepatic vein. As a result, only the right inferior hepatic vein was
      preserved as a drainage vein. Because the perivertebral plexus and the azygos
      vein were both well developed, neither veno-venous bypass nor IVC reconstruction
      was performed. The developed collateral veins acted as the venous drainage
      pathway to maintain a stable systemic circulation. On the seventh postoperative
      day, portal vein flow dramatically decreased and the patient tended to liver
      failure. Prostaglandin E(1) (PGE(1)) was administrated via the superior
      mesenteric artery. The portal flow then gradually increased and liver failure was
      avoided. Six months after the operation, she was re-admitted due to obstructive
      jaundice and presented with complete stenosis of the common bile duct (CBD). The
      jaundice persisted and liver dysfunction progressed. The patient died seven
      months after the operation. The confluence of the right inferior vein and the IVC
      could have been deformed, causing outflow blockade. The intrinsic shunt was not
      good enough to act as the drainage pathway, and IVC reconstruction may have been
      needed.

PMID- 15995821
TI  - Corpus callosum atrophy is associated with gait disorders in patients with
      leukoaraiosis.
AB  - Cognitive impairment and gait disturbances are the most frequent clinical
      findings in patients with leukoaraiosis (LA). Corpus callosum (CC) atrophy has
      been associated with dementia in patients with LA, as well as with gait
      disturbances in patients with normal pressure hydrocephalus. We investigated, in
      patients with LA, the possible association between gait impairment and CC
      atrophy, taking into account cognitive deficits and the other brain lesions
      commonly present in these patients. Thirty patients (M:F=21:9; mean age 72.5+/
      6.3 years) with gait disturbances and brain CT images consistent with LA
      underwent an assessment of gait and a cognitive assessment of global and
      selective functions. Magnetic resonance imaging (MRI) was used to measure
      thickness and area of the CC, total LA volume, lacunar infarcts and size of
      lateral ventricles. We examined the effect of every MRI change on each
      performance measure. Reduction of CC thickness, particularly that of the anterior
      segment, had a significant effect on severity of gait impairment, as measured
      using the gait scale's score. It was independent of any other brain changes
      revealed by MRI, including LA. An independent, significant association was also
      found between CC area and the Left Hand Praxis test results. In patients with LA,
      CC atrophy is associated with gait impairment independently of LA and other brain
      abnormalities usually present in these patients.

PMID- 15995822
TI  - Multimodal electrophysiologic follow-up study in 3 mutated but presymptomatic
      members of a spinocerebellar ataxia type 1 (SCA1) family.
AB  - The objective was to determine the progression of nervous system involvement in
      spinocerebellar ataxia type 1 (SCA1). Three presymptomatic members of an Italian
      SCA1 family underwent molecular analysis and showed the SCA1 mutation. They were
      defined as "at risk/mutated" individuals. A clinical and electrophysiologic 7-9
      year follow-up was performed. The Inherited Ataxia Progression Scale was used for
      clinical staging. Sensory and motor conduction velocities, somatosensory evoked
      potentials and transcranial magnetic stimulation were performed at least three
      times in each subject. Clinical examination showed the early corticospinal
      pathway involvement. Electrophysiologic investigations confirmed that at the
      asymptomatic stage only magnetic motor cortex stimulation was abnormal and
      rapidly worsened with time. Somatosensory pathway studies showed a later
      involvement and a light sensory-motor neuropathy was the last electrophysiologic
      abnormality to be recognised. These data confirm that SCA1 phenotype is
      characterised by early and prevalent pyramidal tract involvement and that
      peripheral neuropathy is a late and moderate complication.

PMID- 15995823
TI  - The economic burden of stroke in Italy. The EcLIPSE Study: Economic Longitudinal
      Incidence-based Project for Stroke Evaluation.
AB  - Stroke is the second most common cause of death in the world. The aim of this
      study is to estimate stroke's direct costs and productivity losses in Italy from
      a societal perspective and to explain cost variability. A prospective
      observational multicentre cost of illness study was designed. Four hundred and
      forty-nine consecutive patients admitted because of acute first-ever stroke in 11
      Italian hospitals were enrolled. Costs and outcomes were assessed at patients'
      enrollment, and at 3, 6 and 12 months after discharge. Overall, social costs in
      the first six months following the attack were euros 11,600 per patient; 53% of
      this was health care costs, 39% non-health care costs and the remaining 8%
      productivity losses. Age, level of disability and type of hospital ward were the
      most significant predictors of six-month social costs. The acute phase counted
      for more than 50% of total health care costs, leaving the remaining 50% to the
      post-acute phase, indicating that follow-up should be on the agenda of policy
      makers also.

PMID- 15995824
TI  - Stroke units and general wards in seven Italian regions: the PROSIT study.
AB  - PROSIT (research PROject on Stroke services in ITaly) is a study performed to
      evaluate number and work organisation of acute in-hospital services (stroke
      units, SU) and general wards (GW), in seven Italian regions (Liguria, Lombardia,
      Lazio, Veneto, Friuli-Venezia-Giulia, Emilia Romagna, Toscana), which have a
      population of 29,169,811 inhabitants and a relative ratio of 225/100,000
      hospitalisations for acute stroke. The registers of hospital discharges from
      January to December 1999 were looked at identify to services recording at least
      50 acute stroke discharges (DRG14) per year. A structured questionnaire
      investigating stroke service characteristics was submitted to the doctors in
      charge of the identified units and completed in the presence of an external
      observer between October 2000 and February 2001. SUs were identified as units
      with dedicated beds (at least 80%) and team (at least 1 physician and 1 nurse)
      for acute stroke patients. SUs are still uncommon in many Italian regions because
      only, as 7% of the wards evaluated were found to be a SU and less than 10% of
      acute stroke patients resulted to be admitted to a SU. Great heterogeneity was
      found between the different regions surveyed. The most striking differences
      between SUs and GW were related to the staffing and care organisation, with
      higher number/patients ratio in SUs as far as physicians and nurses, speech
      therapists and social workers were concerned.

PMID- 15995825
TI  - Maternal exposure to the antiepileptic drug vigabatrin affects postnatal
      development in the rat.
AB  - The objective was to investigate, in the rat, the effects of maternal exposure to
      vigabatrin (VGB) on the postnatal motor-cognitive behaviour of the offspring. We
      used an experimental evaluator-blind, placebo-controlled study in the rat. Ten
      pregnant rats were divided into five groups and treated with different doses of
      VGB (250, 500, 750, 1000 mg/kg/day) or placebo from gestation day (GD) 6 to GD10.
      After delivery, 56 pups (40 pups prenatally exposed to VGB and 16 pups exposed to
      placebo) were evaluated for motor-cognitive behaviour throughout postpartum day
      40. At the end of testing sessions the animals were sacrificed and brain tissues
      processed for biochemical analysis of GABA levels. Body weight of pups and young
      rats whose mothers were treated with a dose of 750 mg/kg/day were significantly
      lower both at birth and during the whole postnatal life with respect to the
      control groups. Young rats of this group exhibited impaired performance in both
      the open-field and water maze tasks. Brain GABA contents were dramatically
      increased in this group of rats. No other significant nutritional, biochemical or
      behavioural changes were observed after treatments with doses of VGB lower than
      750 mg/kg/day. The exposure to a dose of 1000 mg/kg caused abortion. Maternal
      exposure to VGB at relatively high doses (750 mg/kg/day) is likely to cause some
      important changes of the nutritional status during the pre- and postnatal life.
      Thus, the biochemical and cognitive abnormalities observed in this study could be
      related to some disturbances of brain development induced by malnutrition and/or
      to a disturbance of neuronal programming of the gabaergic system.

PMID- 15995826
TI  - Who is who: Italian norms for visual recognition and identification of
      celebrities.
AB  - Age-, education- and sex-adjusted norms are provided for two new
      neuropsychological tests, namely (i) Face Recognition (guess of familiarity) and
      (ii) Person Identification (biographical contextualisation). Sixty-three pictures
      of celebrities and 63 of unknown people were selected following two interwoven
      criteria(1): the realm of their celebrity (i.e., entertainment, culture and
      politics) and the period of celebrity acquisition (i.e., pre-war, post-war and
      contemporary). Both media- and education-dependent knowledge of celebrity were
      considered. Ninety-eight unpaid healthy participants aged between 50 and 93 years
      and with at least 8 years of formal education took part in this study. Reference
      is made to serial models of familiar face/persons processing. Recognition is held
      to tackle the activity of Personal Identity Nodes (PINs) and identification of
      the Exemplar Semantics Archives. Given the seriality of the reference model, the
      Identification Test is embedded in the Recognition test. This entailed that only
      previously recognised faces were employed to achieve norms for identification.

PMID- 15995827
TI  - The Frontal Assessment Battery (FAB): normative values in an Italian population
      sample.
AB  - The Frontal Assessment Battery (FAB) is a short cognitive and behavioural six
      subtest battery for the bedside screening of a global executive dysfunction;
      although recently devised, it is already extensively used thanks to its ease of
      administration and claimed sensitivity. The aim of the present study was to
      derive Italian normative values from a sample of 364 control subjects (215 women
      and 149 men) of different ages (mean: 57.4+/-17.9 years; range: 20-94 years) and
      educational level (mean: 10.4+/-4.3 years; range: 1-17 years); the Mini Mental
      State Examination (MMSE) was concurrently administered. Multiple linear
      regression analysis revealed significant effects for age and education whereas
      gender was not significant; thus, from the derived linear equation, a correction
      grid for FAB raw scores was built. Based on nonparametric techniques, inferential
      cut-off scores were subsequently determined and equivalent scores (ES) computed.
      Test-restest and interrater reliabilities were both satisfactory. Interestingly,
      MMSE was significantly correlated with FAB raw scores, whereas adjusted scores
      were not. The present data may improve the accuracy in the use of the FAB both
      for clinical and research purposes.

PMID- 15995828
TI  - The spectrum of mutations for CADASIL diagnosis.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to
      mutations of the Notch3 gene at the chromosome locus 19p13. The clinical spectrum
      includes recurrent ischaemic episodes, cognitive deficits, migraine and
      psychiatric disorders. The histopathological hallmark of CADASIL is accumulation
      of electron dense granules (GOM) in the media of arterioles. MRI reveals
      extensive cerebral white matter lesions and subcortical infarcts. CADASIL was
      initially thought to be a rare disorder, but increasing numbers of families have
      been identified; therefore, it is likely that CADASIL is still largely
      underdiagnosed. Here we report an update on mutations of the Notch3 gene and some
      information on the pathogenesis of the disease.

PMID- 15995829
TI  - Electrophysiological evidence by single fibre electromyography of neuromuscular
      transmission impairment in a case of Miller Fisher syndrome.
AB  - Miller Fisher syndrome is an autoimmune neuropathy characterised by ataxia,
      areflexia and ophthalmoplegia, with minimal if any limb weakness, and in the
      majority of cases by high titres of IgG anti-GQ1b ganglioside antibodies. In
      vitro electrophysiological experiments have demonstrated that these antibodies
      induce a transmission blockade at neuromuscular junction either pre- or post
      synaptically. We report the case of a 63-year-old man with MFS that shows blood
      serum negative for anti-GQ1b but presents an impairment of neuromuscular
      transmission detected by single fibre electromyography. To the best of our
      knowledge, this represents the first case in the literature using jitter
      technique and suggests that other antibodies may be involved in the function of
      motor end plates by bindings to the synaptic membranes.

PMID- 15995830
TI  - Primary leptomeningeal gliomatosis: case report and review of the literature.
AB  - A 62-year-old woman developed dysphasia, signs of intracranial hypertension and
      seizures. An MRI scan evidenced extra-axial contrast enhancement in the absence
      of mass lesions. CSF analysis was negative for malignant cytology and viral or
      bacterial microbiology. In the absence of other evidence, considering the acute
      clinical onset and MRI picture, a viral encephalitis was suspected and antiviral
      therapy was started, however, with no effect. Death occurred three weeks after
      presentation because of acute brain swelling. Autopsy revealed leptomeningeal
      gliomatosis and diffuse parenchymal infiltration at the cerebellar and left
      temporal lobe. Primary leptomeningeal gliomatosis (PLMG) is a rare event. The
      reported case and the reviewed literature evidence that clinical signs at
      presentation are non-specific, CSF negative findings are common, the diagnosis is
      always delayed and the prognosis dismal.

PMID- 15995831
TI  - Multiple sclerosis coinciding with Machado-Joseph disease.
AB  - Although inflammatory demyelination is considered to be the key feature in
      multiple sclerosis (MS) pathogenesis, histopathological investigations and MRI
      studies recently highlighted the extent of neuronal damage that occurs even in
      the early stages of the disease. We report the unusual case of a patient with
      Machado-Joseph disease (MJD; spinocerebellar ataxia (SCA) III) and discuss this
      coincidence in light current pathogenetic paradigms of CNS autoimmunity.

PMID- 15995832
TI  - Pergolide improvement in neuroleptic-resistant Tourette cases: various mechanisms
      causing tics.
AB  - The objective was to report the possibility that in Tourette's disorder (TD) the
      same pathways may not be involved in all patients. Tics in three children
      affected with TD showed no improvement after treatment with several neuroleptic
      drugs (D2 blockers) at appropriate doses. However, they did improve greatly and
      persistently with pergolide treatment. One of the 3 patients showed a less usual
      tic feature, the most relevant of which resembled violent myoclonias of both
      upper limbs. This suggests that in these patients the improvement due to
      pergolide is not linked to an effect on D2-receptors-carrying GABAergic neurons,
      as usually assumed, because the patients did not respond to neuroleptics acting
      in this way. In these 3 cases, unlike in other TD patents, a prevalent action of
      pergolide by pre-synaptic inhibition of dopamine release on D1-receptors-carrying
      GABAergic neurons is suggested. Therefore, direct and indirect pathways could be
      differentially involved in different cases of TD.

PMID- 15995833
TI  - Early onset aggressive hereditary amyloidosis: report of an Italian family with
      TTR Arg47 mutation.
AB  - Arg47 is a rare transthyretin-related (TTR) amyloidosis variant that is
      characterised by polyneuropathy and autonomic failure. We describe an Italian
      family with this mutation whose members (two women and their father) showed a
      rapid progression of the peripheral nervous system involvement and died within 5
      years of clinical onset. Patients with Arg47 or other aggressive TTR amyloidoses
      should be considered high priority patients for orthotopic liver transplantation.

PMID- 15995834
TI  - [Partial breast irradiation after breast-conserving surgery for breast cancer].

PMID- 15995835
TI  - Interobserver delineation variation using CT versus combined CT + MRI in
      intensity-modulated radiotherapy for prostate cancer.
AB  - PURPOSE: To quantify interobserver variation of prostate and seminal vesicle
      delineations using CT only versus CT + MRI in consensus reading with a
      radiologist. MATERIAL AND METHODS: The prostate and seminal vesicles of 13
      patients treated with intensity-modulated radiotherapy for prostatic
      adenocarcinoma were retrospectively delineated by three radiation oncologists on
      CT only and on CT + MRI in consensus reading with a radiologist. The volumes and
      margin positions were calculated and intermodality and interobserver variations
      were assessed for the clinical target volume (CTV), seminal vesicles, prostate
      and three prostatic subdivisions (apical, middle and basal third). RESULTS: Using
      CT + MRI as compared to CT alone, the mean CTV, prostate and seminal vesicle
      volumes significantly decreased by 6.54%, 5.21% and 10.47%, respectively. More
      importantly, their standard deviations significantly decreased by 63.06%, 62.65%
      and 44.83%, respectively. The highest level of variation was found at the
      prostatic apex, followed by the prostatic base and seminal vesicles. CONCLUSION:
      Addition of MRI to CT in consensus reading with a radiologist results in a
      moderate decrease of the CTV, but an important decrease of the interobserver
      delineation variation, especially at the prostatic apex.

PMID- 15995836
TI  - IMRT to escalate the dose to the prostate while treating the pelvic nodes.
AB  - BACKGROUND AND PURPOSE: To assess and quantify the benefit of introducing
      intensity-modulated radiotherapy (IMRT) over conventional approaches to cover the
      pelvic nodes while escalating the dose to the prostate gland. MATERIAL AND
      METHODS: The pelvic lymphatics were planned to receive 50 Gy at 2 Gy per fraction
      by four-field box (4FB) technique and standard field blocks drawn on digitally
      reconstructed radiographs (DRR), 4FB with field blocks according to the position
      of pelvic nodes as contoured on serial planning CT slices, or IMRT. The lateral
      fields included three different variations of field blocks to assess the role of
      various degrees of rectal shielding. The boost consisted in 26 Gy in 13 fractions
      delivered via six-field three-dimensional conformal radiotherapy (3DCRT) or IMRT.
      By the combination of a pelvic treatment and boost, several plans were obtained
      for each patient, all normalized to be isoeffective with regard to prostate
      planning target volume (PTV-P) coverage. Plans were compared with respect to dose
      volume histogram (DVH) of pelvic nodes/seminal vesicles-PTV (PTV-PN/SV), rectum,
      bladder and intestinal cavity. Reported are the results obtained in eight
      patients. RESULTS: Pelvic IMRT with a conformal boost provided superior sparing
      of both bladder and rectum over any of the 4FB plans with the same boost. For the
      rectum the advantage was around 10% at V70 and even larger for lower doses.
      Coverage of the pelvic nodes was adequate with initial IMRT with about 98% of the
      volume receiving 100% of the prescribed dose. An IMRT boost provided a gain in
      rectal sparing as compared to a conformal boost. However, the benefit was always
      greater with pelvic IMRT followed by a conformal boost as compared to 4FB with
      IMRT boost. Finally, the effect of utilizing an IMRT boost with initial pelvic
      IMRT was greater for the bladder than for the rectum (at V70, about 9% and 3% for
      the bladder and rectum, respectively). CONCLUSION: IMRT to pelvic nodes with a
      conformal boost allows dose escalation to the prostate while respecting current
      dose objectives in the majority of patients and it is dosimetrically superior to
      4FB. An IMRT boost should be considered for patients who fail to meet bladder
      dose objectives.

PMID- 15995837
TI  - Results of three dimensional conformal radiotherapy and hormonal therapy for
      local recurrence after radical prostatectomy.
AB  - BACKGROUND AND PURPOSE: Analysis of treatment results of combined three
      dimensional conformal radiotherapy (3DCRT) and hormonal therapy in patients with
      locally recurrent prostate cancer after radical prostatectomy. PATIENTS AND
      METHODS: Between 1992 and 1998, 24 patients presented with a rising prostate
      specific antigen (PSA) between 4 and 152 months following radical prostatectomy
      and a local recurrence demonstrated by imaging. Recurrence was biopsy-proven in
      13 cases. All patients were treated with 3DCRT to a total dose of 60-70 Gy. 21
      patients (88%) received adjuvant hormone therapy up to a maximum of 6 months.
      RESULTS: All patients showed a response in PSA values after therapy. Median
      follow-up is 43 months. Overall survival is 80% and 67% at 3 and 5 years,
      respectively. Biochemical control rates are 53% and 38% at 3 and 5 years,
      respectively. 14 patients developed a second PSA relapse. Acute and late
      toxicities, classified with the RTOG score, were moderate. CONCLUSION:
      Radiotherapy and short-term adjuvant hormone therapy represent an effective and
      well-tolerated treatment for locally recurrent prostate cancer after radical
      prostatectomy resulting in good local control. Long-term prognosis in terms of
      biochemical control and disease-specific survival remains poor.

PMID- 15995838
TI  - Comparative treatment planning on localized prostate carcinoma conformal photon-
      versus proton-based radiotherapy.
AB  - PURPOSE: To assess the potential benefit of proton-beam therapy in comparison to
      3-D conformal photon therapy and photon- based intensity-modulated radiotherapy
      (IMRT) in prostate carcinoma for various stages of disease. MATERIAL AND METHODS:
      In five patients a 3-D conformal proton-based (two lateral beams) irradiation
      technique was compared with 3-D conformal photon-beam radiotherapy (four-field
      box) and IMRT (seven beams). For each patient different target volumes (CTVs)
      were defined according to early, intermediate and advanced stages of disease: CTV
      I consisted of the prostate gland, CTV II encompassed prostate and basis of
      seminal vesicles, and CTV III the prostate and seminal vesicles. Corresponding
      planning target volumes PTV I-III were defined by uniformly adding a margin of 5
      mm to CTV I-III. Dose-volume histograms (DVHs) were analyzed for the different
      PTVs and various organs at risk (OARs), i.e., rectal wall, bladder, both femoral
      heads. In addition, maximum and mean doses were derived for the various
      structures and irradiated non-target tissue volumes were compared for PTV I-III
      and the different irradiation techniques. Finally, dose conformity and target
      dose homogeneity were assessed. RESULTS: With photon- and proton-based
      radiotherapy techniques similar dose distributions were determined for PTV I-III:
      mean and maximum PTV dose values were between 99-104% and 102-107% of the
      normalized total doses (70 Gy), respectively. Conformity indices varied from 1.4
      to 1.5 for the photon techniques, whereas for proton-beam radiotherapy values
      ranged from 1.1 to 1.4. Both the 3-D conformal and the IMRT photon treatment
      technique resulted in increased mean doses (approximately 40-80%) for OARs when
      compared to protons. With both photon techniques non-target tissue volumes were
      irradiated to higher doses (mean dose difference > or = 70%) compared to proton
      beam radiotherapy. Differences occurred mainly at the low and medium dose levels,
      whereas in high dose levels similar values were obtained. In comparison to
      conformal 3-D treatments IMRT reduced doses to OARs in the medium dose range,
      especially for the rectal wall. CONCLUSION: IMRT enabled dose reductions to OARs
      in the medium dose range compared to 3-D conformal radiotherapy. A rather simple
      two-field proton-based treatment technique further reduced doses to OARs compared
      to photon-beam radiotherapy. The advantageous dose distribution of proton-beam
      therapy for prostate cancer may result in reduced side effects, which needs to be
      confirmed in clinical studies.

PMID- 15995839
TI  - The CFSE distribution assay is a powerful technique for the analysis of radiation
      induced cell death and survival on a single-cell level.
AB  - BACKGROUND AND PURPOSE: To analyze radiation sensitivity of cells and to monitor
      cellular responses to irradiation, sensitive test systems for cell death and
      proliferation on a single-cell level are required. Traditionally, cellular
      radiation survival is measured using the clonogenic assay as the gold standard.
      Here it is reported, that labeling of cells with 5-(and 6-)carboxyfluorescein
      diacetate succinimidyl ester (CFDASE) can be used as a highly sensitive assay to
      determine cellular response toward irradiation on a single-cell level. MATERIAL
      AND METHODS: The human malignant cell lines U937 (myelomonocytic, nonadherent),
      SW48 and SW480 (colorectal, adherent) were labeled with CFDASE, irradiated with
      either UVB (0-540 mJ/cm(2)), or X-rays (0-16 Gy). Cell death and proliferation
      were monitored by cytofluorometry and compared to the clonogenic assay for
      adherent SW48 and SW480 cells. RESULTS: Dividing nonadherent U937 cells displayed
      a shift in carboxyfluorescein (CF) fluorescence in parallel with an increased
      cell count indicating cell proliferation. By comparison, UVB-irradiated U937
      cells did not show a shift in CF fluorescence and an increase in cell count
      indicating cell-cycle arrest. In a mixed cell culture, only the nonirradiated
      cells divided and concomitantly reduced their fluorescence. Calculating the
      number of cell divisions it was observed that the nonirradiated cells underwent
      approximately six cell divisions within 7 days, whereas the irradiated cells
      divided only once on average. The adherent SW480 colorectal cells showed a more
      pronounced cell-cycle arrest after irradiation with 240 mJ/cm(2) UVB as compared
      to cells treated with X-ray up to 16 Gy. Furthermore, the CFSE assay also
      discriminated colorectal cell lines of different intrinsic radiosensitivities and
      yielded results comparable to the standard clonogenic assay. CONCLUSION: Analysis
      of CF distribution can be employed as a powerful add-on to the clonogenic assay
      to simultaneously monitor cellular responses toward irradiation on a single-cell
      level. It constitutes an add-on to the clonogenic assay, especially for
      nonadherent cells.

PMID- 15995840
TI  - Radiation exposure of extracranial organs at risk during stereotactic linac
      radiosurgery.
AB  - BACKGROUND AND PURPOSE: Stereotactic radiosurgery of intracranial tumors and
      vascular malformations can be performed by either a linear accelerator (Linac) or
      gamma knife. The aim of this first study on patients was to determine the
      radiation exposure of organs at risk and assess the risk for late effects
      including secondary tumors and/or hereditary disorders after stereotactic Linac
      radiosurgery. MATERIAL AND METHODS: Thermoluminescent dosimetry (TLD)
      measurements were done on 21 consecutively admitted patients with various
      intracranial lesions scheduled for Linac radiosurgery. The TLD chips were placed
      on the eyelid, thyroid, breast and the regions of the ovary or testes. RESULTS:
      The mean doses in organs at risk were 276 +/- 200 mGy (eye lens), 155 +/- 83 mGy
      (thyroid), 47 +/- 22 mGy (breast), 20 +/- 12 mGy (ovary), and 9 +/- 3 mGy
      (testes). The doses decreased significantly with a larger distance from the
      isocenter. CONCLUSION: The absorbed doses to the extracranial organs at risk in
      patients undergoing Linac radiosurgery were very low, ranging from 0.025%
      (testes) to 0.76% (eye lens) of the mean maximum target dose (36 Gy).
      Nevertheless, while the majority of radiosurgery patients have benign tumors or
      arteriovenous malformations and their life expectancy is long, all doses should
      be kept as low as reasonably achievable. This could be accomplished by the use of
      modern irradiation techniques including conformal beams with micro-multileaf
      collimator and avoiding beams directed to the trunk.

PMID- 15995841
TI  - Dosimetric quality assurance for intensity-modulated radiotherapy feasibility
      study for a filmless approach.
AB  - PURPOSE: Test and comparison of various 2-D real-time detectors for dosimetric
      quality assurance (QA) of intensity-modulated radiotherapy (IMRT) with the vision
      to replace radiographic films for 2-D dosimetry. MATERIAL AND METHODS: All IMRT
      treatment plans were created with the Konrad software (Siemens OCS). The final
      dose calculation was also carried out in Konrad. A Mevatron Primus (Siemens OCS)
      linear accelerator which provides 6-MV and 15-MV highenergy photon beams was used
      for the delivery of segmented multileaf-modulated IMRT. Three different 2-D
      detectors, each based on a different physical (interaction) principle, were
      tested for the field-related IMRT verification: (1) the MapCheck diode system
      (Sun Nuclear), (2) the I'mRT QA scintillation detector (Scanditronix/Wellhofer),
      and the Seven29 ionization chamber array (PTW). The performance of these detector
      arrays was evaluated against IMRT dose distributions created and calculated with
      Konrad and the results obtained were compared with film measurements performed
      with radiographic films (EDR2, Kodak). Additionally, measurements were performed
      with point detectors, such as diamond, diodes (PTW) and ionization chambers (PTW,
      Scanditronics/ Wellhofer) and radiochromic films (GafChromic film MD55, ISP).
      RESULTS: The results obtained with all three 2-D detector systems were in good
      agreement with calculations performed with the treatment-planning system and with
      the standard dosimetric tools, i.e., films or various point dose detectors. It
      could be shown that all three systems offer dosimetric characteristics required
      for performing field-related IMRT QA with relative dose measurements. The
      accuracy of the 2-D detectors was mostly +/- 3% normalized to dose maximum for a
      wide dynamic range. The maximum deviations did not exceed +/- 5% even in regions
      with a steep dose gradient. The main differences between the detector systems
      were the spatial resolution, the maximal field size, and the ability to perform
      absolute dosimetric measurements. CONCLUSION: Commercial 2-D detectors have the
      potential to replace films as an "area detector" for field-related verification
      of IMRT. The on-line information provided by the respective systems can even
      improve the efficiency of the QA procedures.

PMID- 15995842
TI  - [Giant mucocele of all paranasal sinuses with massive bilateral globe
      displacement].
AB  - Although of benign nature and slowly progressive, paranasal sinus mucoceles may,
      depending on their localization, cause a multitude of ophthalmological symptoms
      due to compression and displacement of adjacent tissue. Here we report the
      unusual case of a patient suffering from a progressively growing giant mucocele
      that developed years after ENT surgery and that was neglected for almost 2
      decades despite massive symptoms. This case report demonstrates the importance of
      including mucoceles of the paranasal sinuses into the differential diagnosis of
      unilateral or bilateral proptosis.

PMID- 15995843
TI  - [Intermittent ciliary block as a result of haemodialysis].
AB  - We report the case of a patient who experienced recurrent elevations of
      intraocular pressure during haemodialysis. We measured a rise in intraocular
      pressure of 10-12 mmHg after dialysis. The lens showed intumescence, and a
      ciliary block was detected by means of Orbscan II. Within 6 h findings had
      normalized. Changes in serum osmolarity due to haemodialysis may result in fluid
      shifts between different compartments. Decrease of serum osmolarity during
      dialysis may lead to lens swelling and thus cause a ciliary block. This may end
      with regression of the lens swelling.

PMID- 15995844
TI  - [The development of concepts of female (in)continence. Pathophysiology,
      diagnostics and surgical therapy].
AB  - The integral theory postulates that defect ligaments and fascias, which impair
      the supporting function of the vaginal wall, can cause stress urinary
      incontinence as well as urgency and voiding dysfunction. The anatomical and
      pathophysiologic basis for these dysfunctions are presented. Voiding dysfunctions
      can be treated by the substitution of defect structures using the principle of
      "restoration of structure leads to restoration of function". Essential elements
      of this therapeutic algorithm are suburethral vaginal slings (retropubic or
      transobturatoric), further a posterior sling, which runs through the fossa
      ischiorectalis and suspends the vaginal vault near the sacrospinal ligaments,
      thus reconstructing defect uterosacral ligaments. In cystoceles, lateral and
      medial defects can be restored by ventral meshes, which are fixed at the arcus
      tendineus fasciae pelvis by lateral transobturatoric slings. The use of
      polypropylene slings and meshes is well-founded because they are well tolerated
      in the tissues and through the development of scar tissue lead to neoligaments
      with long-lasting therapeutic effects.

PMID- 15995845
TI  - Procalcitonin as a predictor of severe appendicitis in children.
AB  - The aim of this study was to assess the diagnostic value of procalcitonin (PCT)
      in 212 children with appendicitis and compare it with that of the standard
      diagnostic modalities, C-reactive protein (CRP) level, leukocyte count, and
      abdominal ultrasound findings, in relation to the surgical and histological
      findings of the appendix. A PCT value of >0.5 ng/ml was found to be indicative of
      perforation or gangrene with 73.4% sensitivity and 94.6% specificity, a CRP level
      of >50 mg/l and a leukocyte count of >10(4)/mm3 were useful diagnostic markers
      for perforation, while abdominal ultrasonography had a sensitivity of 82.8% and a
      specificity of 91.2% for detecting appendicitis with imaging findings. PCT
      measurement seems to be a useful adjunctive tool for diagnosing acute necrotizing
      appendicitis or perforation, and surgical exploration will probably be required
      in patients with PCT values >0.5 ng/ml.

PMID- 15995846
TI  - Health-related quality of life of diabetic foot ulcer patients and their
      caregivers.
AB  - AIMS/HYPOTHESIS: The effect of a foot ulcer on health-related quality of life
      (HRQoL) of patients with diabetes mellitus and their caregivers is unclear, and
      was therefore evaluated prospectively in this multicentre study. METHODS: HRQoL
      according to the 36-item health-related quality of life questionnaire (SF-36) of
      294 patients (ulcer duration > or = 4 weeks) and 153 caregivers was analysed at
      baseline (time-point zero [T0]), once the ulcer was healed or after 20 weeks
      (time-point 1 [T1]), and 3 months later (time-point 2 [T2]). Patients with severe
      ischaemia were excluded. RESULTS: The mean age of the patients was 60 years, 72%
      were male, and time since diagnosis of diabetes was 17 years. Patients reported a
      low HRQoL on all SF-36 subscales. At T1, HRQoL scores in physical and social
      functioning were higher in patients with a healed vs a non-healed ulcer (p<0.05).
      At T2, these differences were larger, with higher scores for physical and social
      functioning, role physical and the physical summary score (all p<0.05). Within
      group analysis revealed that HRQoL improved in different subscales in patients
      with a healed ulcer and worsened in patients with a persistent ulcer from T0 to
      T2 (all p<0.05). The caregivers of patients with a persisting ulcer had more
      emotional difficulties at T2. CONCLUSIONS/INTERPRETATION: Diabetic patients with
      a healed foot ulcer had a higher HRQoL than patients with a persisting ulcer.
      Healing of a foot ulcer resulted in a marked improvement of several SF-36
      subscales 3 months after healing (from T0 to T2). HRQoL declined progressively
      when the ulcer did not heal. A diabetic foot ulcer appeared to be a large
      emotional burden on the patients' caregivers, as well.

PMID- 15995847
TI  - Lack of effect of intermittently administered sodium fusidate in patients with
      newly diagnosed type 1 diabetes mellitus: the FUSIDM trial.
AB  - AIMS/HYPOTHESIS: We evaluated in a double-blind study the effect of early
      treatment with the immunomodulatory drug fusidin in patients with newly diagnosed
      type 1 diabetes mellitus. METHODS: Twenty-eight adults with newly diagnosed type
      1 diabetes were included in the study. The patients were randomly assigned
      (computer-generated random number sequence) to two experimental groups. Patients
      allocated to the fusidin (FUS) group (n=15) received sodium fusidate (fusidin;
      500 mg orally three times daily for 4 weeks). Subsequently the drug was given at
      the same dose and scheduled for two consecutive weeks a month followed by 2 weeks
      a month without the drug for 20 weeks. Subjects allocated to the placebo (PCB)
      group (n=13) received placebo according to the same schedule and conditions
      described for sodium fusidate in the FUS group. All patients received a diet
      adjusted to their age and BMI, and intensive insulin therapy. RESULTS: There were
      no statistically significant differences between the FUS and PCB groups in beta
      cell function, evaluated by basal and glucagon-stimulated C-peptide values during
      the follow-up (24 and 48 weeks). There was also no difference between the two
      groups in insulin requirement after 48 weeks (0.4+/-0.2 and 0.4+/-0.2 U/kg body
      weight for the FUS and PCB groups, respectively). Antibody titres, including
      insulin autoantibodies, were similar in the two groups during the follow-up.
      CONCLUSIONS/INTERPRETATION: Early treatment of newly diagnosed type 1 diabetes
      patients with intermittently administered fusidin failed to influence the natural
      course of the disease.

PMID- 15995848
TI  - The Rap-B-Raf signalling pathway is activated by glucose and glucagon-like
      peptide-1 in human islet cells.
AB  - AIMS/HYPOTHESIS: Glucose and glucagon-like peptide-1 have been shown to activate
      extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase in beta
      cells. We examined the contributions of the small GTPases Rap and Ras and the
      serine-threonine kinases B-Raf and Raf-1 to the activation of these kinases in
      human islet cells. METHODS: The expression of Rap, Ras, B-Raf and Raf-1 in human
      islets was examined by immunohistochemistry and immunoblotting. Human islets were
      incubated in glucose at concentrations of 2.5 and 15 mmol/l and were stimulated
      with 10 nmol/l glucagon-like peptide-1. The activation of ERK and Raf kinases was
      examined by phosphorylation-specific antibodies and immuno-complexed kinase
      assays. The activation of Rap and Ras was determined by pull-down assays.
      Stimulation of phosphoinositide 3-kinase was detected by immuno-complexed lipid
      kinase assays. RESULTS: Extracellular-regulated kinase and protein kinase B (a
      downstream target of phosphoinositide 3-kinase) were activated in islets
      stimulated with glucose and glucagon-like peptide-1. In these islets, the Rap-B
      Raf signalling pathway was activated preferentially compared with Ras and Raf-1,
      and activated Rap and B-Raf mediated ERK stimulation in kinase assays in vitro.
      In addition, Rap rather than Ras mediated activation of phosphoinositide 3-kinase
      in islets stimulated with glucose and glucagon-like peptide-1.
      CONCLUSIONS/INTERPRETATION: In human islet cells, glucose and glucagon-like
      peptide-1 activate the Rap and B-Raf signalling module, which mediates ERK
      activation in assays in vitro. Rap also activates phosphoinositide 3-kinase,
      delineating central roles for Rap and B-Raf as therapeutic targets for beta cell
      growth in diabetes mellitus.

PMID- 15995849
TI  - [Migraine therapy].
AB  - With more than 8 million sufferers in Germany alone, migraine is one of the most
      frequent medical disorders. Recent discoveries in the pathophysiology and
      genetics of headaches, as well as specific developments in pharmacology, have
      paved the way for a significant improvement in both acute migraine treatment and
      migraine prevention. Within the group of 5-HT(1B/D)-agonists (triptans), seven
      substances with 23 dosages and formulations have been approved in Germany that
      allow the customized treatment of migraine attacks. In addition, several new
      drugs such as valproic acid or topiramate are now available as drugs of first
      choice for migraine prevention, as well as the well established beta blockers,
      thus enabling the physician to tailor the preventative treatment according to the
      individual needs of the patient.

PMID- 15995850
TI  - Identification of reaction networks for bioprocesses: determination of a
      partially unknown pseudo-stoichiometric matrix.
AB  - In this paper we propose a methodology to determine the structure of the pseudo
      stoichiometric coefficient matrix K in a mass balance-based model and to identify
      its coefficients from a set of available data. The first stage consists in
      estimating the number of reactions that must be taken into account to represent
      the main mass transfer within the bioreactor. This provides the dimension of K.
      Then we propose a method to directly determine the structure of the matrix (i.e.
      mainly its zeros and the signs of its coefficients). These methods are
      illustrated with simulations of a process of lipase production from olive oil by
      Candida rugosa.

PMID- 15995851
TI  - On a systematic procedure for the predetermination of macroscopic reaction
      schemes.
AB  - Macroscopic modeling of biological cell cultures involves two major steps: (a)
      the selection of a reaction scheme and (b) the determination of the reaction
      kinetics. The first step is usually accomplished based on prior knowledge,
      experimental investigation and trials and errors. This procedure can be time
      consuming, and more importantly, can lead to the selection of a reaction scheme
      omitting some important reaction pathways, or at the opposite, incorporating too
      many details (at least considering the data at hand and the modeling objectives).
      This paper addresses this modeling problem, and aims at the development of a
      method for systematically evaluating (i.e. setting up and comparing) all
      potential reaction schemes, based on a set of measured components, and satisfying
      structural identifiability properties. One of the main features of the method is
      that the yield (or pseudo-stoichiometric) coefficients can be estimated
      independently of the kinetics. The method is illustrated with simulation results
      and an experimental case study.

PMID- 15995852
TI  - Detection of phthalate metabolites in human saliva.
AB  - In assessment of exposure to environmental contaminants, the use of
      unconventional matrices is becoming an increasingly important area of research.
      Saliva is one of the most promising alternative matrices because its collection
      is easy, noninvasive, and inexpensive. In this study, we measured the salivary
      concentrations of 14 phthalate metabolites in 39 anonymous adult volunteers using
      isotope-dilution, automated solid phase extraction-high performance liquid
      chromatography-tandem mass spectrometry. Seven phthalate metabolites were
      detected at the concentrations ranging from below the limit of detection (<1
      ng/mL) to 10.6 ng/mL for phthalic acid, 3.1 ng/mL for monomethyl phthalate (MMP),
      91.4 ng/mL for monoethyl phthalate (MEP), 65.8 ng/mL for mono-n-butyl phthalate
      (MBP), 17.9 ng/mL for mono-iso-butyl phthalate, 353.6 ng/mL for monobenzyl
      phthalate, and 6.8 ng/mL for mono-2-ethylhexyl phthalate (MEHP). The frequency of
      detection was highest for MBP (85%) and lowest for MMP (8%). The median salivary
      MBP level in this group of adults was higher than the median serum MBP level in
      another non-occupationally exposed human adult population in the United States,
      whereas, the median salivary levels of MEP and MEHP were lower than the
      corresponding median serum levels. The frequency of detection and the salivary
      levels of each phthalate monoester in this study population were lower than the
      frequency of detection and urinary level of the same monoester in the general US
      population. Although urine is preferred for exposure assessment to non-persistent
      chemicals such as phthalates, the similar levels in serum and saliva suggest that
      saliva could be used as a surrogate matrix for measuring the bioavailable dose of
      phthalates in biomonitoring studies.

PMID- 15995853
TI  - Platelet-activating factor (PAF) involvement in acetaminophen-induced liver
      toxicity and regeneration.
AB  - Acetaminophen-induced toxicity has been attributed to cytochrome P-450-generated
      metabolites, which covalently modify target proteins. However, the mechanism of
      liver injury pathogenesis needs to be further elucidated. Platelet-activating
      factor (PAF) is one of the mediators involved in inflammatory tissue alterations
      associated with acute liver failure. In this study, alterations in blood PAF
      levels and the serum activity of PAF-acetylhydrolase (PAF-AH) were investigated
      over the time course of liver injury and regeneration induced by acetaminophen
      treatment in rats. The administration of a toxic dose of acetaminophen (3.5 g/kg)
      in rats caused acute hepatic injury, as evident by alterations of biochemical
      (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of
      inflammation and apoptosis) indices between 20 and 40 h post-treatment. The
      hepatic damage was followed by liver regeneration, made evident by three
      independent indices ([3H]thymidine incorporation into hepatic DNA, liver
      thymidine kinase activity and hepatocyte mitotic index), presenting a peak at 72
      h. The PAF levels were elevated at 24 and 28 h, presenting a remarkable peak at
      32 h post-treatment. PAF-AH activity presented different kinetics to that of PAF.
      The enzyme activity was relatively low at all time points examined before the
      rise in PAF activity, peaking later, at 72, 84 and 96 h. Our data demonstrate
      that PAF is involved in the pathogenesis of acute liver failure and in augmented
      compensatory liver tissue repair post-acetaminophen treatment. However, the
      putative role of PAF during liver toxicity and regeneration remains to be
      established.

PMID- 15995855
TI  - White biotechnology for green chemistry: fermentative 2-oxocarboxylic acids as
      novel building blocks for subsequent chemical syntheses.
AB  - Functionalized compounds, which are difficult to produce by classical chemical
      synthesis, are of special interest as biotechnologically available targets. They
      represent useful building blocks for subsequent organic syntheses, wherein they
      can undergo stereoselective or regioselective reactions. "White Biotechnology"
      (as defined by the European Chemical Industry [
      http://www.europabio.org/white_biotech.htm ], as part of a sustainable "Green
      Chemistry,") supports new applications of chemicals produced via biotechnology.
      Environmental aspects of this interdisciplinary combination include: Use of
      renewable feedstock Optimization of biotechnological processes by means of: New
      "high performance" microorganisms On-line measurement of substrates and products
      in bioreactors Alternative product isolation, resulting in higher yields, and
      lower energy demand In this overview we describe biotechnologically produced
      pyruvic, 2-oxopentaric and 2-oxohexaric acids as promising new building blocks
      for synthetic chemistry. In the first part, the microbial formation of 2
      oxocarboxylic acids (2-OCAs) in general, and optimization of the fermentation
      steps required to form pyruvic acid, 2-oxoglutaric acid, and 2-oxo-D-gluconic
      acid are described, highlighting the fundamental advantages in comparison to
      chemical syntheses. In the second part, a set of chemical formula schemes
      demonstrate that 2-OCAs are applicable as building blocks in the chemical
      synthesis of, e.g., hydrophilic triazines, spiro-connected heterocycles,
      benzotriazines, and pyranoic amino acids. Finally, some perspectives are
      discussed.

PMID- 15995856
TI  - [Accidental urban hypothermia. Severe hypothermia of 20.7 degrees C].
AB  - In emergency medicine accidental hypothermia (<35 degrees C) is a common
      epiphenomenon of many medical conditions. In contrast, severe hypothermia (<28
      degrees C) occurs very seldom and presents a difficult medical situation. Here we
      present a female patient with severe urban hypothermia (core temperature of 20.7
      degrees C) and circulatory arrest. An overview of the emergency treatment,
      rewarming strategy with extracorporeal circulation and the clinical course will
      be given. The survival of the patient and the favorable neurological outcome will
      be discussed considering the current literature. Due to the paucity of treatment
      guidelines or clear prognostic criteria of withholding or withdrawing treatment
      in severe hypothermia, the decision of prolonged resuscitation and rewarming
      strategy is solely dependent on the individual judgement and medical experience
      of the physician. The positive clinical outcome which can be gleaned from case
      reports or single retrospective studies should encourage the emergency physician
      to selectively rewarm a severe hypothermic patient with extracorporeal
      circulation under prolonged CPR.

PMID- 15995854
TI  - Strategies for the engineered phytoremediation of toxic element pollution:
      mercury and arsenic.
AB  - Plants have many natural properties that make them ideally suited to clean up
      polluted soil, water, and air, in a process called phytoremediation. We are in
      the early stages of testing genetic engineering-based phytoremediation strategies
      for elemental pollutants like mercury and arsenic using the model plant
      Arabidopsis. The long-term goal is to develop and test vigorous, field-adapted
      plant species that can prevent elemental pollutants from entering the food-chain
      by extracting them to aboveground tissues, where they can be managed. To achieve
      this goal for arsenic and mercury, and pave the way for the remediation of other
      challenging elemental pollutants like lead or radionucleides, research and
      development on native hyperaccumulators and engineered model plants needs to
      proceed in at least eight focus areas: (1) Plant tolerance to toxic elementals is
      essential if plant roots are to penetrate and extract pollutants efficiently from
      heterogeneous contaminated soils. Only the roots of mercury- and arsenic-tolerant
      plants efficiently contact substrates heavily contaminated with these elements.
      (2) Plants alter their rhizosphere by secreting various enzymes and small
      molecules, and by adjusting pH in order to enhance extraction of both essential
      nutrients and toxic elements. Acidification favors greater mobility and uptake of
      mercury and arsenic. (3) Short distance transport systems for nutrients in roots
      and root hairs requires numerous endogenous transporters. It is likely that root
      plasma membrane transporters for iron, copper, zinc, and phosphate take up ionic
      mercuric ions and arsenate. (4) The electrochemical state and chemical speciation
      of elemental pollutants can enhance their mobility from roots up to shoots.
      Initial data suggest that elemental and ionic mercury and the oxyanion arsenate
      will be the most mobile species of these two toxic elements. (5) The long
      distance transport of nutrients requires efficient xylem loading in roots,
      movement through the xylem up to leaves, and efficient xylem unloading
      aboveground. These systems can be enhanced for the movement of arsenic and
      mercury. (6) Aboveground control over the electrochemical state and chemical
      speciation of elemental pollutants will maximize their storage in leaves, stems,
      and vascular tissues. Our research suggests ionic Hg(II) and arsenite will be the
      best chemical species to trap aboveground. (7) Chemical sinks can increase the
      storage capacity for essential nutrients like iron, zinc, copper, sulfate, and
      phosphate. Organic acids and thiol-rich chelators are among the important
      chemical sinks that could trap maximal levels of mercury and arsenic aboveground.
      (8) Physical sinks such as subcellular vacuoles, epidermal trichome cells, and
      dead vascular elements have shown the evolutionary capacity to store large
      quantities of a few toxic pollutants aboveground in various native
      hyperaccumulators. Specific plant transporters may already recognize gluthione
      conjugates of Hg(II) or arsenite and pump them into vacuole.

PMID- 15995857
TI  - Comment on "Prognostic value of relative adrenal insufficiency after out-of
      hospital cardiac arrest" by Pene et al.

PMID- 15995859
TI  - Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently
      when combined with danaparoid sodium than with unfractionated heparin.
AB  - OBJECTIVE: This study investigated the potential benefits of combination therapy
      using antithrombin (AT) with danaparoid sodium (DA) compared with the use of AT
      with unfractionated heparin (UFH) in the treatment of sepsis. METHODS: Rats
      infused with lipopolysaccharide were treated with either DA alone, AT alone, AT
      plus DA, AT plus UFH, or human serum albumin as controls. AT (125 U/kg) was
      injected into the AT group immediately after lipopolysaccharide infusion. The
      AT/DA and AT/UFH groups received the same dose of AT in conjunction with either
      DA (400 U/kg) or UFH (400 U/kg). The status of the mesenteric microcirculation
      was examined by intra-vital microscopy and the laboratory indices of coagulation,
      inflammation, and organ dysfunction were measured. RESULTS: The coagulation
      markers were improved following the administration of DA or UFH. The decreases in
      the WBC counts were significantly suppressed in the AT/DA group. The elevation of
      IL-6 decreased in the AT, DA, and AT/DA groups (all p<0.01) but not in the AT/UFH
      group. The prostaglandin I2 levels were significantly elevated only in the AT/DA
      group (p<0.05). The WBC adhesion was significantly suppressed in the DA, AT/UFH,
      and AT/DA groups (p<0.05), and the RBC velocity was best maintained in the AT/DA
      group with no associated increase in capillary hemorrhage. The elevation of ALT
      and BUN significantly improved only in the AT/DA group. ONCLUSION: Organ
      dysfunction can thus be alleviated by even moderate doses of AT replacement when
      co-administered with DA.

PMID- 15995860
TI  - Horseradish peroxidase-based organic-phase enzyme electrode.
AB  - An organic-phase enzyme electrode (OPEE) based on horseradish peroxidase (HRP)
      immobilized within Nafion on spectroscopic graphite was investigated in
      acetonitrile. The amperometric electrode response to hydrogen peroxide and cumene
      hydroperoxide present was found to be the result of the reduction of oxygen,
      produced upon enzymatic decomposition of both hydroperoxides (i.e., by the
      catalase-like activity of HRP). The electrode response was found to depend
      linearly on the hydroperoxide concentration up to 700 microM within the range of
      potentials from -200 to -400 mV (versus Ag|AgCl). Detection limits of
      approximately 45 microM for H2O2 and 100 microM for cumene hydroperoxide were
      determined under the selected experimental conditions. Nernstian dependence (the
      open circuit voltage of HRP-based electrode versus logarithm of H2O2
      concentration) was obtained between 0.2 and 2.0 mM, with a slope of approximately
      23 mV per logarithmic unit, suggesting a catalase-like, two-electron
      disproportionation of the substrate in acetonitrile.

PMID- 15995861
TI  - Label-free characterisation of oligonucleotide hybridisation using reflectometric
      interference spectroscopy.
AB  - The potential of a label-free detection method, reflectometric interference
      spectroscopy (RIfS), for temperature-dependent DNA hybridisation experiments (for
      example in single nucleotide polymorphism (SNP) analysis) is investigated.
      Hybridisations of DNA, peptide nucleic acid (PNA), and locked nucleic acid (LNA)
      to a single stranded DNA were measured for several temperatures, and the melting
      curves and temperatures were calculated from the changes in optical thickness
      obtained. These measurements were performed by hybridising surface-immobilised
      single stranded oligomers with their complementary ssDNA or with ssDNA containing
      SNPs at different temperatures. DNA was compared to its analogue oligomers PNA
      and LNA due to their stability against nuclease. A comparison of melting
      temperatures demonstrated the higher binding affinities of the DNA analogues.
      Moreover, a continuous melting curve was obtained by first hybridising the
      functionalised surface with its complementary DNA at room temperature and then
      heating up in-flow. Measurement of the continuous melting curve was only possible
      due to the insensitivity of the RIfS method towards temperature changes. This is
      an advantage over other label-free detection methods, which are based on
      determining the refractive index.

PMID- 15995862
TI  - Preconcentration and fluorimetric determination of polycyclic aromatic
      hydrocarbons based on the acid-induced cloud-point extraction with sodium
      dodecylsulfate.
AB  - The acid-induced cloud-point extraction (CPE) technique based on sodium
      dodecylsulfate (SDS) micelles has been used for preconcentration of ten
      representatives of polycyclic aromatic hydrocarbons (PAHs) for the following
      fluorescence determination. The effect of the acidity of solution, SDS and
      electrolyte concentrations, centrifugation time and rate on the two-phase
      separation process and extraction percentages of PAHs have systematically been
      examined. Extraction percentages have been obtained for all PAHs after CPE ranged
      from 67 to 93%. Pyrene was used as a fluorescent probe to monitor the
      micropolarity of the surfactant-rich phase compared with SDS micelles and this
      allows one to conclude that water content in micellar phase after CPE is reduced.
      The spectral, metrological and analytical characteristics of PAH fluorimetric
      determination after acid-based CPE with sodium dodecylsulfate are presented.
      Advantages provided by using CPE in combination with fluorimetric determination
      of PAHs are discussed. The determination of benz[a]pyrene in tap water is
      presented as an example.

PMID- 15995863
TI  - Rapid screening for ethyl carbamate in stone-fruit spirits using FTIR
      spectroscopy and chemometrics.
AB  - Ethyl carbamate (EC, urethane, C2H5OCONH2) is a known genotoxic carcinogen of
      widespread occurrence in fermented food and beverages with the highest
      concentrations being found in stone-fruit spirits. Time-consuming procedures
      requiring extraction and gas chromatographic-mass spectrometric determination are
      regarded as reference procedures for the analysis of EC in alcoholic beverages.
      In this study, the rapid method of Fourier transform infrared (FTIR) spectroscopy
      in combination with partial least-squares (PLS) regression using selected
      wavelength bands is applied for the first time to the screening analysis of EC in
      stone fruit spirits (analysis time only 2 min). Apart from the actual content of
      EC in the sample, additional information was available from the FTIR spectra.
      This included data concerning the EC precursor hydrocyanic acid (HCN) and the
      maximum EC concentration which could be formed during storage. The PLS procedure
      was validated using an independent set of samples (Q(2) = 0.71-0.76, SEP = 0.42
      0.67). The method was found to lack the accuracy required for a quantitative
      determination; it could only be used semi-quantitatively in the context of a
      screening analysis. If a rejection level of 0.8 mg L(-1) is applied as cut-off,
      overall correct classification rates of 85-91% for the calibration set and 77-85%
      for the validation set were achieved. False negative results can be avoided by
      lowering the cut-off to 0.6 mg L(-1). Through use of FTIR screening, 60-70% of
      all samples can be classified as negative and removed, leaving only conspicuous
      analysis results exceeding cut-off to be confirmed by complex and labour
      intensive reference analyses.

PMID- 15995864
TI  - Reconstruction of the medial patellofemoral ligament for painful patellar
      subluxation in distal torsional malalignment: a case report.
AB  - Complex two-level rotational malalignment of the lower extremity can cause
      maltracking of the patella with anterior knee pain. Double derotation osteotomy
      would correct the underlying pathology. However, it carries a high risk of
      complications such as nerve and vessel damage. We report a case of rotational
      malalignment in the femur and the tibia associated with trochlear dysplasia,
      which causes painful patellar instability. The patient was successfully treated
      with reconstruction of the medial patellofemoral ligament and lateral release.
      Although the malrotation was not addressed, the position of the patella was
      corrected, and no dislocation occurred during a follow-up of 10 months.

PMID- 15995865
TI  - Molecular dissection of interspecific variation between Gossypium hirsutum and G.
      barbadense (cotton) by a backcross-self approach: II. Fiber fineness.
AB  - A backcross-self population from a cross between Gossypium hirsutum and G.
      barbadense was used to dissect the molecular basis of genetic variation governing
      two parameters reflecting lint fiber fineness and to compare the precision of
      these two measurements. By applying a detailed restriction fragment length
      polymorphism (RFLP) map to 3,662 BC(3)F(2) plants from 24 independently derived
      BC(3) families, we were able to detect 32 and nine quantitative trait loci (QTLs)
      for fiber fineness and micronaire (MIC), respectively. The discovery of larger
      numbers of QTLs in this study than previously found in other studies based on
      F(2) populations grown in favorable environments reflects the ability of the
      backcross-self design to resolve smaller QTL effects. Although the two
      measurements differed dramatically in the number of QTLs detected, seven of the
      nine MIC QTLs were also associated with fiber fineness. This supports other data
      in suggesting that fiber fineness more accurately reflects the underlying
      physical properties of cotton fibers and, consequently, is a preferable trait for
      selection. "Negative transgression," with the majority of BC(3)F(2) families
      showing average phenotypes that were poorer than that of the inferior parent,
      suggests that many of the new gene combinations formed by interspecific
      hybridization are maladaptive and may contribute to the lack of progress in
      utilizing G. barbadense in conventional breeding programs to improve upland
      cotton.

PMID- 15995866
TI  - QTL analysis for fruit yield components in table grapes (Vitis vinifera).
AB  - A segregation population of 184 genotypes derived from a pseudo-testcross of
      table grapes (Vitis vinifera), together with 203 AFLP and 110 SSR markers was
      used to detect quantitative trait loci (QTLs) for fruit yield components.
      Diffferent QTLs, a low percentage of phenotypic variance explained by the QTLs
      detected and QTL instability over years were detected for each fruit yield
      component. These results confirm the complex genetic architecture of the yield
      components in grapevine due to the perennial nature of this species, which has to
      adapt to yearly variations in climate. Phenotypic correlation analyses between
      fruit yield components were also performed. The negative correlation between
      berry weight and the number of berries per cluster seems to have an indirect
      negative effect on cluster weight, as revealed by the path coefficient analysis;
      however, this negative correlation was not supported at the molecular level
      because no coincident QTLs were observed between these traits. Nonetheless, the
      possibility to select seedless genotypes with large berries without affecting
      cluster weight needs to be substantiated in future experiments because factors
      such as sample size and heritability might influence QTL identification in table
      grapes.

PMID- 15995867
TI  - [Plaques opalines: a rare form of secondary syphilis of the oral mucous
      membrane].
AB  - A 37 year old woman presented with a 4-month history of "plaques opalines" of the
      oral mucosa complaining of a rough feeling in her mouth and burning when
      swallowing. On the basis of clinical, histological and serological details and
      especially the presence of generalized indolent lymphadenopathy, the diagnosis of
      secondary syphilis was made. Although plaques opalines are a relatively rare
      manifestation of secondary syphilis, they can occasionally be the only sign and
      are important in the differential diagnostic considerations of gray-white mucosal
      lesions, especially with current continuing rise of syphilis incidence in Central
      Europe.

PMID- 15995868
TI  - [Hygienic and dermatologic aspects of hand disinfection and prophylactic skin
      antisepsis].
AB  - Hygienic hand disinfection must be carried out after all patient-care activities
      associated with contamination risks, as well as when moving from contaminated to
      clean body sites, after contact with environmental surfaces in the immediate
      vicinity of patients, after glove removal and before aseptic procedures.
      Preparatory handwashing (for about 10 seconds) to mechanically remove soil and
      bacterial spores should be performed at least 10 minutes before surgical hand
      disinfection. This allows time for the normalization of increased skin hydration,
      a prerequisite for effective hand disinfection. Depending on the manufacturer's
      instructions, application times of 1.5, 3 or 5 minutes can be observed. The
      regular use of skin care and skin protection products can help to prevent toxic
      skin irritation. For skin antisepsis the recommended exposure times are > or =15
      seconds before subcutaneous injections, > or =1 minute before puncture of joints
      and body cavities as well as preoperatively, and > or =10 minutes on skin areas
      rich in sebaceous glands. For all 3 indications, alcohol-based formulations are
      the agents of choice.

PMID- 15995869
TI  - Misidentification of cardiac vagal pre-ganglionic neurons after injections of
      retrograde tracer into the pericardial space in the rat.
AB  - We evaluated whether pericardial injections of the retrograde tracers cholera
      toxin subunit B (CTb) or Fast Blue (FB) reliably labelled cardiac vagal pre
      ganglionic neurons. Injections of CTb into the pericardial space of the rat
      labelled neurons in both the external and compact formations of the nucleus
      ambiguus. Most labelled neurons were found in the compact formation of the
      nucleus ambiguus, and the majority of these, and only these, expressed
      immunoreactivity for calcitonin gene-related peptide. This distribution of
      labelled neurons and their immunohistochemical properties is characteristic of
      oesophageal motoneurons. Examination of the oesophagus following intra
      pericardial CTb applications revealed strong labelling of motor end plates within
      the skeletal muscle of the thoracic but not the abdominal oesophagus. When a
      second retrograde tracer, FB, was injected into the abdominal oesophagus,
      labelled somata were found adjacent to CTb-labelled neurons in the compact
      formation of the nucleus ambiguus. No co-localisation of tracers was found, but
      identical proportions of calcitonin gene-related peptide (CGRP) immunoreactivity
      were observed in both groups of neurons. FB injected into the pericardial space
      labelled intra-cardiac neurons but not brainstem neurons. We conclude that intra
      pericardial, and perhaps sub-epicardial, injections of some retrograde tracers
      are likely to label a subset of oesophageal, as well as cardiac, vagal motor
      neurons in the brainstem.

PMID- 15995870
TI  - Neurochemical characterization of nervous elements innervating the body wall of
      earthworms (Lumbricus, Eisenia): immunohistochemical and pharmacological studies.
AB  - The distribution and chemical neuroanatomy of nervous elements and certain
      pharmacological-physiological characteristics of the innervation of the body wall
      in earthworms are described. Solitary sensory bipolar cells can be found among
      the epithelial cells. These bipolar cells contain serotonin, tyrosine
      hydroxylase, histamine, gamma-amino-butyric acid (GABA), Eisenia
      tetradecapeptide, proctolin or rhodopsin in various combinations. In the body
      wall, the plexus sub-muscularis is composed of nerve fibres only, whereas the
      plexus sub-epithelialis and muscularis also contain solitary nerve cells. These
      cells display histamine, GABA or neuropeptide Y immunoreactivity. The fibres of
      the three plexuses are reactive to serotonin, histamine, Eisenia
      tetradecapeptide, proctolin, GABA and neuropeptide Y antibodies. FMRFamide
      immunoreactive fibres of the plexus muscularis originate from the central nervous
      system, whereas axons containing the other studied molecules are derived from
      both peripheral and central structures. High pressure liquid chromatography
      assays have revealed serotonin, dopamine and histamine in the body wall.
      Contractions of the body wall musculature can be elicited with serotonin and
      FMRFamide. Serotonin-evoked contractions are suppressed by the application of
      GABA. Serotonin acts both directly on the muscle cell receptors and indirectly
      through initiating transmitter release from the nervous elements, whereas the
      FMRFamide-induced contractions seem to be mediated through the muscle cell
      receptors only. The pharmacological profiles of the serotonin and GABA receptors
      resemble those of the vertebrate 5-HT(3) and GABA(B) receptor types. Our findings
      indicate that both the sensory and efferent system of the annelid body wall
      operate by means of a variety of neuroactive compounds, suggesting a complex role
      of signalling systems in the regulation of this organ.

PMID- 15995871
TI  - Mutation analysis of the HFE gene associated with hereditary hemochromatosis in a
      Venezuelan sample.
AB  - The frequency of the C282Y, H63D and S65C alleles of the HFE gene was determined
      in a sample of the Venezuelan population. Two new sets of primers were tested for
      amplifying the regions mapping these mutations, and genotyping was performed by
      restriction fragment length polymorphism (RFLP). DNA sequencing was used to
      validate the RFLP analysis. Serum ferritin levels were also determined. Two
      hundred and fourteen individuals were tested, extracting DNA from whole blood
      cells (n=177) or from serum (n=37). The frequency of heterozygous subjects was
      3.7, 18.2 and 1.7% for the C282Y, H63D and S65C mutations, respectively, and the
      allele frequencies were 0.019+/-0.01 for C282Y, 0.119+/-0.016 for H63D and
      0.009+/-0.005 for S65C. The results suggest that the admixture of native
      populations with subjects of South European origin might have had an important
      role in the diffusion of HFE alleles in Venezuela. C282Y homozygous subjects were
      not found in this study. No HFE genotype studied here was associated with a
      significant elevation of serum ferritin concentrations, except for C282Y/H63D
      compound heterozygote found in one asymptomatic male. This finding supports the
      theory that the H63D mutation could be involved in alterations of iron parameters
      when inherited together with C282Y. Our results indicate that C282Y homozygotes
      will be rarely detected. Performance of HFE mutation analysis in individuals with
      high iron determinations would be recommended.

PMID- 15995872
TI  - Congenital lobar emphysema and sequestration--treatment by embolization.
AB  - A case of congenital lobar emphysema associated with pulmonary sequestration,
      presenting with respiratory distress in infancy, is reported. The lobar
      hyperinflation was managed by emergency lobectomy. The ipsilateral lower lobe
      affected with vascular sequestration was salvaged by therapeutic embolization,
      thus avoiding the long-term sequelae of pneumonectomy. The case is reported for
      its rarity.

PMID- 15995873
TI  - [Metatarsalgia. Differential diagnosis and therapeutic algorithm].
AB  - Metatarsalgia is explained as localized or more diffuse tenderness beneath the
      metatarsal heads. The pain may be attributed to various etiologies. Pathological
      changes affecting the positional relationship of the metatarsals in the sagittal
      plane can cause increased pressure and friction forces during weight bearing.
      Since the length of the metatarsals displays a wide range of disparity only a few
      pathological settings, i.e., brachymetatarsia, require surgical correction.
      Beside those disorders of positional relationship, metatarsalgia may be due to
      lesser toe deformities, osteonecrosis of a lesser metatarsal head (Koehler's
      disease), and neurological disorders (Morton's neuroma). Apart from the etiology
      increased load, which is transferred to the central metatarsals, can be treated
      successfully with orthotic devices. If conservative measures fail, surgical
      treatment can be indicated. Prior to any operative therapy it is mandatory to
      perform a detailed analysis of the underlying pathology to avoid persistent pain
      or recurrence of the deformity.

PMID- 15995874
TI  - The role of molecular imaging in the development of dendritic cell-based cancer
      vaccines.

PMID- 15995875
TI  - A publicly accessible Monte Carlo database for validation purposes in emission
      tomography.
AB  - Monte Carlo (MC) methods provide ideal data sets to assess reconstruction and
      correction techniques in emission tomography (ET). Although several ET-dedicated
      MC codes are available, their use is hindered by the heavy computation burden
      required for high statistics simulations as well as by the need to adapt the code
      to the purpose of the individual user. In this work a publicly accessible
      database of MC-simulated ET data sets (the MC-ET database) was created and
      published on an Internet web site (http://www.ibfm.cnr.it/mcet/index.html), in
      order to provide MC-simulated data ready to be downloaded and used by researchers
      at different sites with similar evaluation purposes. At present, the MC-ET
      database provides direct access to MC-simulated raw data of unscattered,
      scattered and total events: (a) obtained by different MC codes, (b) relative to
      different radioactive sources, from simple geometrical phantoms to studies of
      normal and pathological subjects and (c) derived from different SPECT and PET
      scanners. The main features of the MC-ET data sets are: (a) validation by
      comparison with measured data, (b) classification according to pre-defined
      database characteristics, (c) common-use file format and (d) easy and free access
      and download.

PMID- 15995876
TI  - Clozapine decreases [3H] CP 55940 binding to the cannabinoid 1 receptor in the
      rat nucleus accumbens.
AB  - Antipsychotic drugs are effective in the treatment of cannabis-induced psychosis,
      but only clozapine appears effective in the treatment of comorbid schizophrenia
      and cannabis use. The unique effects of clozapine on cannabis use could,
      therefore, be due to an as yet unidentified interaction between clozapine and the
      endogenous cannabinoid system. To address this hypothesis, we used in situ
      radioligand binding and quantitative autoradiography with the selective
      cannabinoid CB1 receptor agonist, (-)-cis-3-[2-hydroxy-4-(1,1
      dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (side chain-2,3,4(N)
      3H) ([3H]CP 55940) to measure the density of the CB1 receptor in frontal cortex,
      hippocampus, nucleus accumbens and striatum from rats treated with a variety of
      antipsychotic drugs. Clozapine significantly decreased [3H]CP 55940 binding in
      the nucleus accumbens compared with vehicle after 1 (35.0+/-14.0 vs. 71.2+/-8.5
      fmol/mg estimated tissue equivalent (ete); P = 0.03) and 3 months (42.3+/-4.0 vs.
      71.1+/-16.3 fmol/mg ete; P < 0.04) of treatment, an effect not observed with
      haloperidol, chlorpromazine or olanzapine. In rats treated with clozapine for 3
      months and then left for 1 month without treatment, [3H]CP 55940 binding was not
      different in the nucleus accumbens (100.5+/-22.2 vs. 100.9+/-25.4 fmol/mg ete; P
      > 0.10). By contrast, there were significant increases in accumbal [3H]CP 55940
      binding in rats treated with haloperidol (136.5+/-14.2 fmol/mg ete; P < 0.05),
      chlorpromazine (137.4+/-12.7 fmol/mg ete; P < 0.05) and olanzapine (144.7+/-10.1
      fmol/mg ete; P < 0.01). These data indicate that in the nucleus accumbens
      clozapine differs from other antipsychotic drugs in its effects on [3H]CP 55940
      binding. If these results can be extrapolated into humans, then this effect of
      clozapine on the CB1 receptor may be a mechanism that makes it uniquely effective
      in schizophrenia and comorbid cannabis use.

PMID- 15995877
TI  - Upper reference limits for biomarkers of exposure to aromatic diisocyanates.
AB  - OBJECTIVES: The objectives of this study were to determine the levels of 2,4
      toluenediamine, 2,6-toluenediamine, 1,5-naphthtalenediamine and 4,4'
      methylenediphenyldianiline in hydrolyzed urine and plasma for occupationally
      unexposed workers and to calculate upper reference limits (URLs). These analytes
      are biomarkers of exposure to 2,4-toluene diisocyanate and 2,6-toluene
      diisocyanate (2,4-TDI and 2,6-TDI), 1,5-naphtalene diisocyanate (NDI) and 4,4'
      methylenediphenyl diisocyanate (MDI), respectively. METHODS: The biomarker levels
      were determined in urinary and plasma samples obtained from 121 occupationally
      unexposed workers. Based on these biomarkers levels and the biomarker levels in
      an occupationally exposed group of workers, URLs were calculated. The method used
      for these calculations was based on the receiver operator characteristic (ROC)
      curve method technique, and the URLs were set at the optimum of sum of
      sensitivity and specificity. RESULTS: The URLs for the different diisocyanates
      were calculated to be in the range of 0.1-0.5 microg/L. Occupationally unexposed
      workers had detectable biomarker levels of the diisocyanates investigated.
      Especially abundant was the biomarkers of MDI which were found in 97% of both
      urinary and plasma samples. For the other biomarkers, 0-15% of the unexposed
      workers had detectable levels. The detected levels were mostly close to the limit
      of detection (LOD), but urinary levels of biomarkers of MDI up to 60 times the
      LOD were found. The sensitivities and specificities for classification of the
      workers as occupationally exposed or not, were in the range of 88-100% and 97
      100%, respectively. CONCLUSIONS: The URLs were calculated that may be applicable
      when screening for occupational exposure. A worker with a biomarker level above
      the URL will be classified as occupationally exposed. Biomarkers of aromatic
      diisocyanates, especially biomarkers of MDI, were present among occupationally
      unexposed workers, but the source and nature of the exposure is unknown.

PMID- 15995878
TI  - On cross-sectional questionnaire studies of relationships between psychosocial
      conditions at work and health--are they reliable?

PMID- 15995879
TI  - Preoperative devascularization of a circumferential osteogenic metastasis to the
      upper cervical spine by direct percutaneous needle puncture: a technical note.
AB  - Direct percutaneous needle puncture (DPNP) for presurgical devascularization of
      head and neck as well as skull base tumours is an established, yet not widespread
      method. We present a case of a large and highly vascularized metastasis with
      partial destruction of the first two cervical vertebrae and encasement of the
      spinal cord that was successfully treated by DPNP for preoperative
      devascularization after an attempted endovascular embolization had failed. The
      lesion was safely and effectively devascularized, which facilitated the surgical
      removal. The case presented illustrates the technique and furthermore
      demonstrates its value.

PMID- 15995880
TI  - Improvement on the visualization of cytoskeletal structures of protozoan
      parasites using high-resolution field emission scanning electron microscopy
      (FESEM).
AB  - The association of high resolution field emission scanning electron microscopy
      (FESEM), with a more efficient system of secondary electron (SE) collection and
      in-lens specimen position, provided a great improvement in the specimen's
      topographical contrast and in the generation of high-resolution images. In
      addition, images obtained with the use of the high-resolution backscattered
      electrons (BSE) detector provided a powerful tool for immunocytochemical analysis
      of biological material. In this work, we show the contribution of the FESEM to
      the detailed description of cytoskeletal structures of the protozoan parasites
      Herpetomonas megaseliae, Trypanosoma brucei and Giardia lamblia. High-resolution
      images of detergent extracted H. megaseliae and T. brucei showed the profile of
      the cortical microtubules, also known as sub-pellicular microtubules (SPMT), and
      protein bridges cross-linking them. Also, it was possible to visualize fine
      details of the filaments that form the lattice-like structure of the
      paraflagellar rod (PFR) and its connection with the axoneme. In G. lamblia, it
      was possible to observe the intricate structure of the adhesive disk, funis (a
      microtubular array) and other cytoskeletal structures poorly described
      previously. Since most of the stable cytoskeletal structures of this protozoan
      rely on tubulin, we used the BSE images to accurately map immunolabeled tubulin
      in its cytoskeleton. Our results suggest that the observation of detergent
      extracted parasites using FESEM associated to backscattered analysis of
      immunolabeled specimens represents a new approach for the study of parasite
      cytoskeletal elements and their protein associations.

PMID- 15995881
TI  - [Dentoalveolar trauma. Analysis of 4763 patients with 6237 injuries in 10 years].
AB  - PURPOSE: The purpose of this study was to evaluate the overall place of dental
      trauma in facial injuries. This was a retrospective investigation based on the
      analysis of a large amount of dentoalveolar injuries over a 10-year period.
      PATIENTS AND METHODS: Between 1991 and 2000, 4763 of 9543 patients suffering from
      oral and maxillofacial injuries, sustained dentoalveolar trauma. Records of 6237
      different dental injury patterns were reviewed according to the five main injury
      mechanisms: age, sex, type of injury, cause of accident, and frequency of
      dentoalveolar trauma. They were statistically analyzed using frequency
      distribution, chi-square test, t-test, Mann-Whitney U test, Kolmogorov-Smirnov
      test, and logistic regression analysis. RESULTS: Household and play (2117),
      sports (1533), traffic accidents (438), acts of violence (426), and work-related
      accidents (201) were noted. A total of 4763 patients had 2988 subluxations, 2356
      showed crown fractures, 444 had avulsions, 176 root fractures, 154 intrusions,
      and 119 patients suffered from concussions. This number of patients accounts for
      the prevalence of 49.9% for dentoalveolar trauma among all facial injuries.
      CONCLUSION: Only the analysis of a large number of injuries reveals the risk of
      suffering from dentoalveolar trauma. Due to this fact, preventive methods can be
      recommended and demanded more effectively.

PMID- 15995882
TI  - [Combined sinus lift procedure and lateral augmentation. A treatment concept for
      the surgical and prosthodontic rehabilitation of the extremely atrophic maxilla].
AB  - PURPOSE: This paper describes a surgical and prosthetic procedure for treating
      the extremely atrophic maxilla. It explains a two-staged surgical technique,
      donor and recipient site morbidity, implant survival, and the implant-retained
      prosthetic rehabilitation of the patients. PATIENTS AND METHODS: A total of 57
      consecutive patients were treated with a sinus lifting procedure and a
      simultaneous lateral augmentation using autogenous corticocancellous block and
      particulate bone grafts from the iliac crest. After a 6-month bone healing
      period, a total of 284 endosteal Titanium screw implants were inserted. Following
      a 3-month osseointegration period, the implants were exposed and loaded with
      either fixed or removable prostheses. RESULTS: In three cases a partial bone
      graft loss was observed; however, enosseous implantation was possible as planned.
      During the observation period none of the 284 implants was lost; 3 implants
      exhibited treatable peri-implant infection. Complications at the donor and
      recipient sites were minimal and did not negatively influence the overall
      clinical result of the treatment. CONCLUSION: The combination of sinus lift
      procedure and lateral augmentation for the treatment of the extremely atrophied
      maxilla proved to be a safe method that produces good and reliable clinical
      results.

PMID- 15995883
TI  - One for two? Exchanging implanted pulse generators for deep brain stimulation.
AB  - The use of a dual channel implantable pulse generator (IPG) for deep brain
      stimulation during de novo implantation is now routine in many centers. When the
      generator batteries of bilateral single channel generators expire, the issue of
      whether to exchange two single channel generators for one dual channel generator
      arises. This presents many debatable clinical, practical and fiscal issues. We
      discuss these issues and describe the "one for two" technique we have adopted for
      exchanging IPGs.

PMID- 15995884
TI  - Surgical trauma and immunosuppression: pathophysiology and potential
      immunomodulatory approaches.
AB  - BACKGROUND: Several studies indicate that organ failure is the leading cause of
      death in the postoperative phase after major surgery. An excessive inflammatory
      response followed by a dramatic depression of cell-mediated immunity after major
      surgery appears to be responsible for the increased susceptibility to subsequent
      sepsis. In view of this, most of the scientific and medical research has been
      directed towards measuring the progression and interrelationship of mediators
      after major surgery. Furthermore, the effect of those mediators on cell-mediated
      immune responses has been studied. OBJECTIVE: This article focuses on the effect
      of surgical injury and blood loss on cell-mediated immune responses in
      experimental studies utilizing models of trauma and hemorrhagic shock. The
      findings from those experimental studies will also be correlated with data from
      surgical patients. RESULTS: Recently, a gender-dimorphic immune and organ
      responsiveness in the susceptibility to and morbidity from shock, trauma, and
      sepsis has been found. Androgens have been shown to be responsible for the
      immunosuppression after trauma-hemorrhage in males. In contrast, female sex
      steroids exhibit immunoprotective properties after trauma and severe blood loss.
      CONCLUSION: In view of these findings, clinically relevant therapeutic strategies
      have been developed using the testosterone receptor blocker flutamide and/or
      estrogen or agents with estrogenic effects, i.e., dehydroepiandrosterone, which
      might yield safe and useful therapeutic approaches for the treatment of immune
      depression in surgical patients.

PMID- 15995885
TI  - Long-term results of the surgical treatment of craniopharyngioma: the experience
      at the Policlinico Gemelli, Catholic University, Rome.
AB  - BACKGROUND: Craniopharyngioma (CP) is the most common intracranial non-glial
      tumour observed in pediatric age. Although histologically benign and amenable to
      surgical treatment, its location and relation with vital nervous and vascular
      structures makes the feasibility of a radical resection difficult even in the
      microneurosurgery era. Beside the difficulties experienced when performing tumour
      resection, post-operative complications, such as endocrinological imbalance,
      represent another point that makes CP total excision a challenge. In order to
      avoid such complications, some authors have suggested to renounce to radical
      resection and to rely on post-operative radiation therapy to minimise the risk of
      residual tumour progression. METHODS: We report our experience with 52 children
      and adolescents operated on for CP at the Department of Pediatrics, Section of
      Pediatric Neurosurgery, Catholic University Medical School, Rome, between January
      1985 and December 2002. The study included 14 children <5 years old (five less
      than 2 years of age), 25 between 6 and 10 years old, and 13 more than 10 years
      old. The most common presenting signs were related to endocrinological imbalance
      (35 cases), increased intracranial pressure (32 cases), and to a lesser extent,
      visual compromise (17 cases). Concerning location, CP was intrasellar in three
      cases; sellar/suprasellar with prominent prechiasmatic growth in 24 cases;
      retrochiasmatic/3rd ventricular in 14 cases, and giant (with an extension into
      the middle and/or posterior cranial fossae) in 11 cases. The tumour was managed
      by means of a single surgical approach in 47 cases and with a two-stage operation
      in the remaining five cases. In 11 cases of intrasellar or intra/suprasellar
      midline location, the first surgical approach was done through the
      transsphenoidal route (which represented the first step of a staged operation in
      five instances); in the remaining 41 patients, craniotomy was the first surgical
      procedure. Radical tumour resection was achieved in 40 cases, subtotal (only
      small tumour remnants adherent to the carotid arteries, 3rd ventricle floor or
      visual pathways) in nine, and only partial in the remaining three cases RESULTS:
      Histology demonstrated the adamantinous variant in all cases. Two surgical deaths
      were recorded in this series (both following a transsphenoidal approach): one
      secondary to uncontrollable intra-operative bleeding from the carotid artery, and
      the other to fulminating bacterial meningoencephalitis. Morbidity included
      endocrinological disturbances, namely hypopituitarism and diabetes insipidus, in
      more than 80% of cases, worsening of pre-operative visual deficit in six cases,
      and transitory neurological deficits in five cases. One late death was recorded 2
      years after surgery, secondary to electrolytic imbalance although favoured by a
      major head trauma with subacute subdural haematoma. Nine recurrences occurred 1-8
      years after surgery (three true recurrences, and six re-growths of incompletely
      resected tumours) that required re-operation. Twelve patients underwent
      radiotherapy, six after an initially incomplete tumour resection and six
      following relapse. One patient presented with a malignant thalamic glioma 8 years
      after radiotherapy. At long-term follow-up, all survivors showed good clinical
      condition, even though approximately 60% relied on hormone replacement, and some
      patients presented obesity. Diabetes insipidus has subsided in about 80% of the
      cases; visual deficits improved or remained stable, whereas post-operative
      neurological deficits subsided in all but one patient. CONCLUSION: In our
      experience, radical resection of CP represented the first and almost unique
      treatment modality. Although not insignificant, post-operative mortality and
      morbidity do not seem to represent a major contraindication in attempting a
      radical tumour resection whenever possible. On the other hand, extensive
      hypothalamic involvement should suggest a less aggressive attitude.

PMID- 15995887
TI  - Evaluating visitor-monitoring techniques: a comparison of counting and video
      observation data.
AB  - Two visitor-monitoring methods, video monitoring and counts by human observers,
      were compared in order to identify and evaluate their respective advantages and
      disadvantages. The analysis considered user numbers, user type (walkers, dog
      walkers, bicyclists, and joggers) and group size of visitors. Remarkable
      differences were found between the two methods for user type and use levels. At
      low use levels, evaluations based on video monitoring resulted in fewer single
      bicyclists compared to counts by human observers, whereas at high use levels,
      human observers counted fewer walkers and bikers than video-interpreters. Based
      on this comparative analysis, we derive recommendations for more effective
      visitor-monitoring approaches. All data were collected during a visitor
      monitoring project in the Danube Floodplains National Park in Austria between
      1998 and 1999.

PMID- 15995886
TI  - Landowner satisfaction with the Wetlands Reserve Program in Wisconsin.
AB  - We evaluated ecological monitoring data and landowner perceptions to the
      federally funded Wetlands Reserve Program (WRP) in a three-county region in
      Wisconsin. We surveyed landowner satisfaction, involvement, participation, and
      use of the WRP restoration sites. We found that landowners are satisfied with the
      overall program (mean, 3.6 +/- 0.2 [SE], on a scale of 1-5, with 5 being
      completely satisfied). WRP restorations significantly increased the area of
      wetland within the sites surveyed, the increase was primarily of fresh meadow
      (736.32 ha after restoration). Satisfaction is related to landowner participation
      during restoration and to the economic incentives provided by the WRP, Landowner
      satisfaction and the number of plant communities after restoration are unrelated
      to each other or to restoration and easement costs per hectare. Survey
      participants recommended some changes to the WRP, including a reduction in the
      tax rate of land enrolled in the WRP, approval for permanent deer stands, and
      increased communication with WRP officials during the restoration. Monitoring
      information collected for WRP restoration sites does not allow assessment of
      whether WRP sites are functionally equivalent to natural sites. We suggest that
      the WRP require a more rigorous monitoring program, including guidelines for
      invasive species control. Managers should also encourage collaborations with
      external researchers and consider restorations within an experimental framework.

PMID- 15995889
TI  - Land-cover change trajectories in northern Ghana.
AB  - Land-cover change trajectories are an emergent property of complex human
      environment systems such as the land-use system. An understanding of the factors
      responsible for land change trajectories is fundamental for land-use planning and
      the development of land-related policies. The aims of this study were to
      characterize and identify the spatial determinants of agricultural land-cover
      change trajectories in northern Ghana. Land-cover change trajectories were
      defined using land-cover maps prepared from Landsat Thematic Mapper dataset
      acquired in 1984, 1992, and 1999. Binary logistic regression was used to model
      the probability of observing the trajectories as a function of spatially explicit
      biophysical and socioeconomic independent variables. Population densities
      generally increased along the continuum of land-use intensity, whereas distance
      from market and roads generally decreased along this continuum. Apparently, roads
      and market serve as incentives for settlement and agricultural land use. An
      increase in population density is an important spatial determinant only for
      trajectories where the dominant change process is agricultural extensification. A
      major response to population growth is an increase in cultivation frequency
      around the main market. Agricultural intensification is highly sensitive to
      accessibility by roads. The increase in land-use intensity is also associated
      with low soil quality. These results suggest the need for policies to restore
      soil fertility for agricultural sustainability. The models also provide a means
      for identifying functional relationships for in-depth analyses of land-use change
      in Ghana.

PMID- 15995888
TI  - Off-target herbicide deposition associated with treating individual trees.
AB  - There are a wide variety of different herbicide treatment methods used to remove
      single trees. Each method (cut-stump, basal, foliar) has a unique amount of off
      target disturbance that should be considered in selecting a treatment for use in
      management. We quantified the amount of off-target deposition that resulted from
      four conventional herbicide application methods: 1) basal, 2) cut-stump, 3) high
      volume, hydraulic foliar, and 4) low-volume, backpack foliar. Basal and cut-stump
      herbicide treatments deposited up to 200 and 4000 times more herbicide (a.i. per
      unit area) at groundline than the low-volume and high-volume foliar treatments,
      respectively. On a per tree basis, basal and cut-stump treatments deposited
      nearly six times more total herbicide than high-volume foliar, and 68 times more
      than low-volume foliar. All of the herbicide deposited off-target landed within
      0.6 m of the basal and cut-stump treatments, 3.7 m with the low-volume foliar,
      and 7.3 m with high-volume foliar methods. Off-target herbicide deposition
      resulted in affected areas with killed or damaged vegetation ranging in size from
      0.36 m2 (cut stump) to 7.08 m2 (high-volume foliar). Deposition amounts and
      affected areas were greater with larger trees, compared to smaller ones. We
      observed that 48% of the total amount of herbicide applied per plot was deposited
      off-target with cut-stump treatment, compared to only 4% to 11% for the other
      treatments. We suspect this difference is due to applicator error with the cut
      stump treatment, likely related to the type of spray device used to apply the
      treatment.

PMID- 15995890
TI  - Environmental auditing and the role of the accountancy profession: a literature
      review.
AB  - This review of the literature on environmental auditing and the potential role of
      accountants distinguishes between compliance audits and audits of the
      environmental management system. After an extensive introduction to the concept,
      this review focuses on the similarities and differences between an environmental
      audit and a financial statement audit. The general approach to both types of
      audits is similar, except that environmental audits are largely unregulated. Both
      audits place an emphasis on the evaluation of control systems, which is an
      argument in favor of external auditors playing a role in environmental audits.
      Another argument for including external accountants is their code of ethics.
      However, these professionals seem to be reluctant to enter the field of
      environmental auditing. It is argued that this reluctance is because of a lack of
      generally accepted principles for conducting environmental audits. If external
      accountants are engaged in environmental auditing, they should be part of
      multidisciplinary teams that also include scientists and engineers to avoid a too
      strong focus on procedures. Rather than treating these audits as totally
      different, it is proposed that there be a move towards integrated, or even
      universal, audits.

PMID- 15995891
TI  - Transport and urban air pollution in India.
AB  - The rapid growth in motor vehicle activity in India and other rapidly
      industrializing low-income countries is contributing to high levels of urban air
      pollution, among other adverse socioeconomic, environmental, health, and welfare
      impacts. This paper first discusses the local, regional, and global impacts
      associated with air pollutant emissions resulting from motor vehicle activity,
      and the technological, behavioral, and institutional factors that have
      contributed to these emissions, in India. The paper then discusses some
      implementation issues related to various policy measures that have been
      undertaken, and the challenges of the policy context. Finally, the paper presents
      insights and lessons based on the recent Indian experience, for better
      understanding and more effectively addressing the transport air pollution problem
      in India and similar countries, in a way that is sensitive to their needs,
      capabilities, and constraints.

PMID- 15995892
TI  - Watershed management and organizational dynamics: nationwide findings and
      regional variation.
AB  - Recent attention has focused on resource management initiatives at the watershed
      scale with emphasis on collaborative, locally driven, and decentralized
      institutional arrangements. Existing literature on limited selections of well
      established watershed-based organizations has provided valuable insights. The
      current research extends this focus by including a broad survey of watershed
      organizations from across the United States as a means to estimate a national
      portrait. Organizational characteristics include year of formation, membership
      size and composition, budget, guiding principles, and mechanisms of decision
      making. These characteristics and the issue concerns of organizations are
      expected to vary with respect to location. Because this research focuses on
      organizations that are place based and stakeholder driven, the forces driving
      them are expected to differ across regions of the country. On this basis of
      location, we suggest basic elements for a regional assessment of watershed
      organizations to channel future research and to better approximate the
      organizational dynamics, issue concerns, and information needs unique to
      organizations across the country. At the broadest level, the identification of
      regional patterns or organizational similarities may facilitate the linkage among
      organizations to coordinate their actions at the much broader river basin or
      ecosystem scale.

PMID- 15995893
TI  - Resource use dynamics and land-cover change in Ang Nhai Village and Phou Phanang
      National Reserve Forest, Lao PDR.
AB  - This study integrated aerial photographs from 1952, 1981, and 1998, and a
      satellite image from 2000 with oral histories and socioeconomic surveys to assess
      changes in forest and land cover in Ang Nhai village, Laos. The study documents
      the history of resource use and changes in household access to resources in the
      village. Three distinctive trends were observed in terms of forest and land cover
      forest degradation, deforestation, and regeneration. Project results suggest that
      land and forest cover change dynamically under different circumstances. The case
      study also points out that integration into the market economy can induce
      intensification of unused lowland areas, while removing pressures from upland
      areas previously used for supplementing agricultural production. In addition, the
      creation of a national reserve forest to restrict local access and forest use was
      an ineffective tool for regulating encroachment and logging activities.

PMID- 15995894
TI  - Land-use and land-cover change and farmer vulnerability in Xishuangbanna
      prefecture in southwestern China.
AB  - This study investigated land-use and land-cover change in three hamlets and two
      state rubber farms in the Nan-e watershed of the Xishuangbanna prefecture of
      Yunnan province in Southwestern China. The overall objective of the study was to
      understand how state policies affected land use and land cover and how changes in
      these variables affected farmer vulnerability to economic, social, and political
      events. Emphasis was placed on the cultivation of rubber (Hevea brasiliensis),
      promoted in southern Yunnan province since the 1950s as a means to meet the
      demands of rapid economic development. The study combined remote sensing analysis
      with secondary data and in-field interviews in order to understand the coupling
      between land-use and land-cover change and farmer vulnerability in light of the
      geographic, historical, and sociopolitical situation.

PMID- 15995898
TI  - Schizophrenia and depression.

PMID- 15995899
TI  - Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or
      discrete genotypes?
AB  - Schizophrenia and affective disorder have been considered to be nosologically and
      etiologically distinct disorders. This postulate is challenged by progress in new
      biological research. Both disorders are strongly influenced by genetic factors;
      thus genetic research is a main contributor to this discussion. We review current
      evidence of the genetic relationship between schizophrenia and affective
      disorders, mainly bipolar disorder (the various genetic research methods have
      been particularly applied to bipolar disorder). Recent family and twin studies
      reveal a growing consistency in demonstrating cosegregation between both
      disorders which is difficult to detect with certainty given the low base rates.
      Systematic molecular genetic search for specific genes impacting on either
      disorder has now identified one gene which is apparently involved in both
      disorders (G72/G30); other candidate genes reveal some evidence to present as
      susceptibility genes with very modest effects for each of both disorders,
      although not consistently so (e. g., COMT, BDNF). There is room for speculation
      about other common susceptibility genes, given the overlap between candidate
      regions for schizophrenia and those for bipolar disorder emerging from linkage
      studies.

PMID- 15995900
TI  - The early course of schizophrenia and depression*.
AB  - OBJECTIVE: Risk factors, emergence and accumulation of symptoms in the untreated
      early course were studied as a basis for understanding the relationship between
      schizophrenia and depression. MATERIALS AND METHODS: 130 representative first
      admissions for schizophrenia were compared retrospectively with 130 individually
      matched first admissions for depressive episodes and with 130 healthy controls.
      RESULTS: Onsets of schizophrenia and severe depression were marked by depressive
      symptoms, followed by negative symptoms and functional impairment. This prodromal
      core syndrome became more prevalent as the disorders progressed, and it
      reappeared in psychotic relapses. Psychotic symptoms emerged late, indicating a
      different and more severe "disease pattern". CONCLUSION: The prevalence of
      depressive symptoms in the general population and at the prodromal stage of
      numerous mental disorders precipitated by various psychological and biological
      factors suggests that depression might be an expression of an inborn mild
      reaction pattern of the human brain. With progressing brain dysfunction more
      severe patterns like psychosis are expressed.

PMID- 15995901
TI  - Depression in the long-term course of schizophrenia.
AB  - Depressive symptoms are quantitatively and qualitatively among the most important
      characteristics of schizophrenia. The following contribution reports on the
      prevalence of depression in 107 patients of the ABC schizophrenia study over 12
      years after first hospital admission, looks into a preponderance of depression at
      certain stages of the illness and the predictive value of depressive symptoms for
      course and outcome. All but one of the 107 patients experienced one to 10
      episodes of depressed mood between index assessment and long-term follow-up. In
      any month of the observation period about 30-35% of the patients presented at
      least one symptom of the depressive core syndrome (depressive mood, loss of
      pleasure, loss of interests, loss of self-confidence, feelings of guilt, suicidal
      thoughts/suicide attempt). Depressive symptoms are particularly frequent during a
      psychotic episode at a rate of approximately 50%. There were moderate but
      statistically significant correlations between the amount of depressive symptoms
      during a psychotic episode and the frequency of relapses, defined by hospital
      admissions as well as the total length of inpatient treatment. Depression
      occurring in the interval was not associated with an increased need for inpatient
      treatment.

PMID- 15995902
TI  - Affective processes in the onset and persistence of psychosis.
AB  - OBJECTIVES: Cognitive models suggest that beliefs and appraisal processes are
      crucially important in the onset and persistence of psychosis. This study
      investigated whether (i) neuroticism increases the risk for development of
      psychotic symptoms, and (ii) a delusional interpretation and/or a depressed
      response to hallucinatory experiences predicts the onset of psychotic disorder.
      METHOD: A general population sample with no lifetime evidence of any psychotic
      disorder was interviewed with the Composite International Diagnostic Interview
      Schedule (CIDI) at baseline and 1 and 3 years later. At year 3, individuals with
      CIDI evidence of psychotic symptoms were interviewed by clinicians to identify
      onset of psychotic disorder. RESULTS: Baseline level of neuroticism increases the
      risk for incident psychotic symptoms. Given the presence of hallucinatory
      experiences at baseline, the increase in risk of having the psychosis outcome was
      much higher in the group with delusional ideation or depressed mood at year 1
      than in those without delusional ideation or depressed mood. CONCLUSION: A
      cognitive style characterised by a tendency to worry increases the risk for newly
      developed psychotic symptoms. Individuals who report hallucinatory experiences
      and react to these with a delusional interpretation and/or negative emotional
      states have an increased risk for developing clinical psychosis.

PMID- 15995915
TI  - Cavity growth in soft adhesives.
AB  - The growth process of cavities nucleated at the interface between a rigid surface
      and a soft adhesive layer has been investigated with a probe method. A tensile
      stress was applied to the highly confined layer resulting in a negative
      hydrostatic pressure in the layer. The statistics of appearance and rate of
      growth of cavities as a function of applied negative stress were monitored with a
      CCD camera. If large germs of cavities were initially present, most of the
      cavities became optically visible above a critical level of stress independent of
      layer thickness. Cavities grew simultaneously and at the same expansion rate as a
      function of applied stress. In the absence of large germs, cavities became
      optically visible one after another, reaching a limiting size controlled by the
      thickness of the layer independently and very rapidly. Although, for each sample,
      we observed a statistical distribution of critical stress levels where a cavity
      expanded, the mean cavitation stress depended both on surface topography and more
      surprisingly on layer thickness. We believe that this new and somewhat surprising
      result can be interpreted with a model for the growth of small germs in finite
      size layers (J. Dollhofer, A. Chiche, V. Muralidharan et al., Int. J. Solids
      Struct. 41, 6111 (2004)). This model is mainly based on the dual notion of an
      energy activated transition from an unexpanded metastable state to an expanded
      stable state and to the proportionality of the activation energy with the elastic
      energy stored in the adhesive layer.

PMID- 15995916
TI  - Antiviral research - 14th International Conference. 8-13 April 2001, Seattle, WA,
      USA.

PMID- 15995917
TI  - Antiviral Research. Retrovirus infections and antiviral research.
AB  - The retrovirus sections of the meeting focused on fundamental, preclinical
      aspects of the development of antiretroviral agents, although some clinical
      developments were also discussed. Novel nucleoside analogs, non-nucleoside
      reverse transcriptase inhibitors, protease inhibitors, as well as preclinical
      data on new molecules that target early stages of HIV-1 infection (HIV
      integrase), were discussed. The meeting comprised plenary presentations, short
      oral communications and over 180 oral or poster presentations, of which more than
      70 dealt with inhibition of retrovirus replication with an emphasis on the human
      immunodeficiency virus (HIV).

PMID- 15995904
TI  - Psychological pathways to depression in schizophrenia: studies in acute
      psychosis, post psychotic depression and auditory hallucinations.

PMID- 15995903
TI  - Antipsychotic and antidepressive effects of second generation antipsychotics: two
      different pharmacological mechanisms?
AB  - Second generation antipsychotics display antidepressive effects in schizophrenic
      patients that are more pronounced than those of traditional neuroleptics and that
      go beyond antidepressive effects secondary to the reduction of positive symptoms.
      The antidepressive potential of second generation antipsychotics is presumably
      related to their pharmacological mechanisms, which differ from those of
      traditional neuroleptics. Among others, 5-HT(2A) antagonism is of special
      relevance for most of the new antipsychotics in this respect. But also special
      interactions with the dopaminergic system, as is the case with amisulpride and
      aripiprazole, or noradrenalin- and/or serotonin-reuptake-inhibition, as with
      ziprasidone and zotepine, should be considered. It can be summarised that the
      antipsychotic and antidepressive effects of second generation antipsychotics are
      mostly based on different pharmacological mechanisms. This might be especially
      true for direct antidepressive effects, i. e. antidepressive effects that are not
      mediated by the reduction of positive symptoms.

PMID- 15995918
TI  - Antiviral Research. Herpes and HIV.

PMID- 15995919
TI  - Antiviral Research. Hepatitis viruses.

PMID- 15995920
TI  - Antiviral Research. Oral presentations and mini symposium.

PMID- 15995921
TI  - Antiviral Research. Poster sessions.

PMID- 15995922
TI  - Clinical microbiology and infectious diseases - 11th European Congress. 1-4 April
      2001, Istanbul, Turkey.
AB  - This report covers the four different sessions of the congress. All sessions
      included the presentation of papers about treatment of respiratory tract
      infections (RTIs). RTIs account for 25% of all the community-acquired infections
      and are the second most frequent among nosocomial infections after urinary tract
      infections. Recent years have witnessed a great increase in resistance to
      antibiotics among pathogens causing RTIs. These changes have rendered several
      'classical' antibiotics less effective in this indication. The drug industry has
      collectively made a great effort to develop new antibiotics to overcome this
      resistance. In the sessions described below, four different antibiotics were
      reviewed for their efficacy in RTIs. A relatively 'older' group comprising a beta
      lactam and beta-lactamase-inhibitor combination was presented for use both in
      community and hospital settings. Two different quinolone antibiotics,
      levofloxacin (Daiichi Seiyaku) and moxifloxacin (Bayer), were the focus of
      another two sessions. In an era of penicillin resistance in Streptococcus
      pneumoniae and increasing importance of atypical organisms causing RTIs, the new
      fluoroquinolone derivatives have become critical agents. These new compounds are
      proving capable not only of eradicating troublesome pathogens, but also achieving
      this faster than any other drug. Finally, a new class of antibiotics, namely
      ketolides, was presented as a novel addition to the macrolide-lincosamide
      streptogramin group. In vitro experiments and clinical experiments with
      telithromycin (Aventis Pharma), the first ketolide antimicrobial, were reported.
      All these presentations demonstrated telithromycin's potent activity against key
      respiratory pathogens, including resistant strains.

PMID- 15995923
TI  - Clinical microbiology and infectious diseases. Antifungal therapy and drug
      resistance.

PMID- 15995924
TI  - Clinical microbiology and infectious diseases. Management of fungal infections.
AB  - Invasive fungal infections are a major cause of morbidity and mortality in
      immunocompromised patients. Despite remarkable progress in mycology, many
      uncertainties and difficulties remain. Invasive fungal infections are difficult
      to diagnose. Noninvasive, rapid diagnostic tools, such as the detection of
      Aspergillus galactomannan antigen in serum or of fungal nucleic acids by
      molecular methods are promising, but are still under investigation. The other
      difficulty in diagnosis is the lack of standard, consistent criteria. Very
      recently, diagnostic criteria based on host factors, as well as clinical features
      and microbiological results, have been proposed. Treatment of invasive fungal
      infections is also problematic. The development of novel antifungal compounds
      constitutes a major advance in antifungal therapy. These include novel azoles
      such as voriconazole (Pfizer), posaconazole (Schering- Plough), and ravuconazole
      (Eisai/Bristol-Myers Squibb), and novel echinocandins such as caspofungin
      (Merck), anidulafungin (Eli Lilly), and micafungin (Fujisawa Pharmaceutical).
      These agents appear more efficacious and less toxic than currently available
      antifungal drugs. However, immune status of the host remains one of the major
      determinants of clinical outcome. This property limits the efficiency of in vitro
      antifungal susceptibility tests in predicting in vivo outcome. Using immune
      system modifiers such as cytokines in combination with antifungal agents is
      beneficial in the improvement of immune status, and thus clinical outcome.

PMID- 15995925
TI  - PPARs - First International Symposium. From basic science to clinical
      applications. 4-7 April 2001, Florence, Italy.

PMID- 15995926
TI  - PPARs. Clinical studies.

PMID- 15995927
TI  - Angiotensin II antagonism: Fourth International Symposium. 3-5 April 2001,
      London, UK.

PMID- 15995928
TI  - Angiotensin II antagonism. Cardioprotection and angiotensin receptor blockade.

PMID- 15995929
TI  - Japanese Respiratory Society - 41st annual meeting. 6-9 April 2001, Tokyo, Japan.
AB  - This was a large meeting, attracting over 4000 delegates, the majority of whom
      came from Japan. For the first time, the meeting had an international program,
      featuring invited speakers from Europe, Asia and the US. The Japanese Respiratory
      Society plans to continue the international program to encourage its young
      scientists and clinical investigators to work closely with overseas
      collaborators. The program featured invited lectures, leading lectures, evening
      symposia, oral presentations and poster presentations.

PMID- 15995930
TI  - Oxidative Stress and Aging - Second International Conference. Technologies for
      assessment and intervention strategies. 2-5 April 2001, Maui, USA.
AB  - The study of oxidative contributions to aging has reached sufficient maturity to
      support the development of interventional strategies designed to forestall or
      reverse protein cross-linking, oxidation of DNA and lipids, and mitochondrial
      senescence associated with chronic pathology and aging. Catalytic antioxidants,
      including combined superoxide dismutase (SOD) and catalase mimics, extend the
      lifespan of oxidatively compromised animals such as Mn-SOD knockout mice, and
      will be entering the clinic for radiation-induced dermatitis. Substituted
      phenacylthiozolium compounds that slow the formation and break extant protein
      cross-linkages formed via Maillard reactions, restoring vascular compliance in
      aged animals, and are showing efficacy in clinical trials. Non-feminizing
      estrogen analogs (eg, 17- alpha estradiol) block cytotoxicity in a host of
      oxidative stress models and moderate neuronal loss in MCAO stroke models.
      Efficacy of the polycyclic phenols is synergistically amplified by glutathione
      supplementation, suggesting that the two function as a redox couple analogous to
      vitamin E and ascorbate. Finally, discovery of novel small molecules designed to
      stabilize mitochondrial function during Ca(2+)-induced oxidative stress, such as
      that occurring during stroke or myocardial ischemia reperfusion, will be
      accelerated by a proprietary fluorescence resonance energy transfer assay
      developed at MitoKor. Maintaining mitochondrial function under these
      circumstances will improve cellular bioenergetic and oxidative status, and hence
      moderate secondary necrosis and apoptosis.

PMID- 15995931
TI  - British Neuroscience Association - 16th National Meeting. 8-11 April 2001,
      Harrogate, UK.

PMID- 15995932
TI  - Cannabinoids - from plant to patient. 5 April 2001, London, UK.
AB  - The active constituents of cannabis (predominantly cannabinoids and possibly
      flavonoids) are more effective than a single cannabinoid in reducing muscle
      spasticity in a multiple sclerosis animal model. Possible interactions include
      both pharmacokinetic and pharmacodynamic effects. Synthetic cannabinoids with
      agonist or antagonist/inverse agonist effects are available with high affinity
      for cannabinoids receptors. Pharmaceutical products that block their uptake and
      metabolism may enhance the endocannabinoid system. Government- and charity-funded
      clinical trials of cannabis are proceeding in pain, both acute (MRC multicenter
      trial) and chronic, and multiple sclerosis (MRC and Multiple Sclerosis Society
      multicenter trials). The design of these trials should enable evidence to be
      presented to regulatory bodies documenting the medicinal uses of standardized
      cannabis plant material.

PMID- 15995933
TI  - IBC's Drug Discovery Technology - Europe 2001. 23-26 April 2001, Stuttgart,
      Germany.
AB  - Specific sectors within the pharmaceutical industry are rapidly changing in
      response to technological advances. Genomics, high-throughput automated
      chemistry, high-throughput screening (HTS), ADME/Tox screening and informatics,
      provide new opportunities, but also create new bottlenecks. In addition, the
      selection and validation of biological targets, the proper design of compound
      libraries, data and knowledge management, and as the last and crucial step, the
      proof of therapeutic relevance by clinical trials, generates an enormous
      financial load on biotechnology and pharmaceutical companies. In the future, drug
      development costs might be reduced due to an ongoing pressure for shorter
      development cycles of new drugs. IBC's Drug Discovery Technology Europe 2001
      conference addressed many aspects relevant to drug discovery technologies, and,
      along with its US partner conference, provides an annual meeting place for
      researchers and company executives to interact and exchange ideas.

PMID- 15995934
TI  - Drug discovery technology. Start-up companies.

PMID- 15995935
TI  - Drugs for the treatment of hyperlipidemia.
AB  - Hyperlipidemia is a major risk factor for the development of cardiovascular
      disease. Considerable evidence suggests that drugs with the ability to lower low
      density lipoprotein-cholesterol also lower cardiovascular deaths. This review
      will focus on new developments in the design of pharmacological agents and
      therapies that can favorably affect hyperlipidemia. A broad range of therapeutic
      agents will be discussed, including food additives, nutraceuticals, conventional
      pharmaceuticals as well as gene therapy. The potential adverse effects caused by
      these agents will also be discussed. Appetite suppressants, intestinal lipase
      inhibitors, inhibitors of dietary cholesterol absorption, inhibitors of
      chylomicron assembly, HMG CoA reductase inhibitors (statins) and adenovirus
      mediated gene therapy are specifically discussed in detail. Treatments and issues
      specific to the elderly and to children are also described. The specific
      application of pharmacogenics to the problem of hyperlipidemia is presented as a
      likely direction for future research emphasis.

PMID- 15995936
TI  - Use of nitric oxide synthase inhibitors for the treatment of inflammatory disease
      and pain.
AB  - This article reviews the recent literature on selective inhibitors of nitric
      oxide synthase (NOS) between 1999 and the first quarter of 2001. The introduction
      highlights the major therapeutic objectives for NOS inhibitors, including
      rheumatoid arthritis (RA), osteoarthritis (OA) and pain. The review attempts to
      cover the structural diversity of small molecule NOS inhibitors currently being
      explored in the pharmaceutical and academic communities.

PMID- 15995937
TI  - PARP inhibitors.
AB  - Poly(ADP-ribose) polymerase (PARP) catalyzes the biochemical conversion of
      nicotinamide adenine dinucleotide (NAD+) to poly(ADP-ribose) and nicotinamide,
      which is a weak feedback inhibitor of the enzyme. Early designs of PARP
      inhibitors were primarily based on mimicking the structure of nicotinamide and
      resulted in the identification and widespread use of benzamide analogs as PARP
      inhibitors. Recent searches for more potent and specific PARP inhibitors,
      facilitated by the crystal structure of the catalytic domain of PARP, led to
      several families of amide and lactam derivatives with multiple ring systems. New
      PARP inhibitors have shown efficacies in several animal disease models of cancer,
      ischemia and inflammation.

PMID- 15995938
TI  - Repifermin. Human Genome Sciences/GlaxoSmithKline.
AB  - Human Genome Sciences (HGS) and GlaxoSmithKline (formerly SmithKline Beecham) are
      developing topical and injectable formulations of repifermin, keratinocyte growth
      factor-2 (KGF-2), also known as fibroblast growth factor-10 (FGF-10) for the
      potential treatment of wound care, oral and intestinal mucositis, and
      inflammatory bowel diseases [385959,396786]. A phase IIb trial of the topical
      formulation in chronic venous ulcers is ongoing, as well as phase II trials for
      the systemic, injectable formulation in ulcerative colitis and in the prevention
      of mucositis after chemotherapy with bone marrow transplantation [352908,368013,
      385959,404294]. In May 2001, UBS Warburg predicted that HGS would receive
      approval of repifermin for the treatment of venous ulcers by yearend 2004,
      mucositis in 2005, and ulcerative colitis in the second half of 2004 [412015]. In
      October 2000, SmithKline Beecham exercised an option to codevelop repifermin for
      phase III trials and beyond [385959,399183]. In May 2001, UBS Warburg valued
      repifermin's worldwide market at 2 billion dollars for treating venous ulcers and
      predicted sales of 33 million dollars in 2004 and 118 million dollars in 2005 for
      this indication. In addition, the analysts regarded repifermin as having
      potential in the treatment of diabetic foot ulcers and pressure ulcers (a market
      valued at over 1.8 billion dollars) and estimated that the drug might earn
      another 103.5 million dollars for these indications in 2005. Furthermore, the
      analysts predicted sales of 6.8 million dollars for repifermin's mucositis
      indication and, for ulcerative colitis, sales of 27.3 million dollars in 2004 and
      54.8 million dollars in 2005. Overall, the analysts estimated that repifermin
      represented a 3.5 billion dollars market opportunity for HGS/ GlaxoSmthKline and
      that commercialization of the drug might earn more than 61 million dollars by
      2004 [412015].

PMID- 15995939
TI  - NT-3. Takeda/Regeneron/Amgen.
AB  - Regeneron, in collaboration with Amgen, is developing neurotrophin-3 (NT-3), a
      neuronal growth factor, for the potential treatment of neuropathies, as well as
      Parkinson's disease (PD). The product was inlicensed from Takeda Chemical
      Industries [179174]. By May 1999, Regeneron had started phase I/II trials in
      patients who suffer constipation due to spinal cord injury, PD or other medical
      conditions [272155,325270]. Initial results, presented at the annual meeting of
      the American Gastroenterological Association in May 1999, showed that NT-3
      exerted strong prokinetic effects [325270], which are thought to be due to
      increased cholinergic activity and a decrease in NO transmission and number of NO
      synthase-positive neurons [368906]. By 1994, Amgen had begun phase I/II trials on
      behalf of Amgen-Regeneron Partners for NT-3 in the US and Canada for the
      potential treatment for peripheral neuropathies [168371]. The mechanism by which
      NT-3 excities intestinal muscle is thought to involve increased non-cholinergic
      contractility, decreased non-adrenergic, non-cholinergic inhibitory
      neurotransmission, and a reduction in the number of NOS-positive neurons
      [368906].

PMID- 15995940
TI  - [Measured quantities in perinatal medicine--the base excess].
AB  - BACKGROUND: There are convincing data from neonatal studies that the base excess
      (BE, mmol/L) measured in capillary or cord blood offers special diagnostic and
      prognostic power in the new-born compromised by hypoxia. For computation of BE
      the hemoglobin concentration (Hb, %), the oxygen saturation (%) and the
      distribution of the fetal fluid compartments are necessary. Until now these three
      factors, which differ in the fetus when compared with adults, have not been taken
      into account using automatic blood gas equipment. This study therefore attempts
      to analyse and verify which BE will offer the best fit with the outcome
      conditions in the newborn. METHODS: Using a cohort of 7701 singletons delivered
      at term by the vaginal route in whom a blood gas analysis in cord blood together
      with Hb measurements were available and plausible, three BE values were computed:
      the ordinary BE (actual BE, according to Radiometer determinations), the BE
      corrected to the real oxygen saturation (BE,oxy) and the BE in the extracellular
      fluid compartment of the fetus (BE,ecff) using the algorithms of O. Siggaard
      Andersen. Moreover, three different oxygen saturation curves for fetal Hb (HbF)
      were applied, namely those of Zander et al., Hellegers and Schruefer and Ruiz et
      al. (Severinghaus). The prognostic potential of the different BE values was
      analysed using a correlation with the APGAR-score after 1 min, the sum of the
      APGAR indices after 1 and 5 min, and additionally with the fetal heart frequency
      (FHF) of the last 30 min ante-partum quantified by a score electronically in a
      group of 342 fetuses. RESULTS: The median of the actual BE in umbilical artery
      blood amounted to -4.9 mmol/L. Correction to the real oxygen saturation of the
      blood sample leads to a median of -7.7 mmol/L. Using three different oxygen
      saturation curves and thus taking into account HbF reveals little influence on
      the numerical values of BE. However, application of the true distribution of
      fetal fluid compartments in the evaluation of BE (BE,ecff) leads to a significant
      reduction of the numerical value of BE (median = -3.2 mmol/L). Computational
      correction of BE using the real oxygen saturation (%) in each fetus leads to a
      important and highly significant increase of the correlation (r and rho) with the
      APGAR indices. The correlation with the FHF score also increased but failed to
      reach significance. CONCLUSIONS: Our data show that, in perinatal medicine, a
      computational correction of BE according to the real oxygen saturation of the
      blood sample is mandatory. An algorithm for HbF should be used. The BE in the
      extracellular fluid compartment does not fit to reality. The determination of the
      Hb concentration in the umbilical blood of each fetus is essential since its
      variability is higher than expected. In legal controversies the computational
      origin of BE should be documented and carefully regarded.

PMID- 15995941
TI  - [Measured quantities in perinatal medicine--the pCO(2)].
AB  - BACKGROUND: For many years the interest of the obstetrician and neonatologist was
      focused on the base excess (BE) in umbilical artery (UA) blood. Otherwise, the
      pCO (2) (mmHg) value which is necessary to compute BE values played only a
      marginal role in our diagnostic evaluation of the fetus/newborn. This is
      especially true for pCO (2) values determined in umbilical venous (UV) blood and
      the feto-matemal interrelations of blood gases and the variables of the acid-base
      balance (ABB) in the fetus and the mother. In this study we have reevaluated the
      importance of fetal pCO (2) measurements and analysed the influence of pCO (2) on
      the actual pH in UA blood, our leading parameter. MATERIAL AND METHODS: The
      variables of fetal ABB and the actual blood gases measured in UA and UV blood of
      7804 neonates, delivered at term without major malformations in vertex
      presentation by the vaginal route, were used. Several generations of acid-base
      equipments from RADIO-METER (Copenhagen) were applied (BMS3 - AMS3). In addition
      arterial acid-base measurements in 101 parturients were performed immediately
      after delivery for analysis of feto-maternal acid-base dependencies. The software
      system JMP (SAS, Carolina, USA) and a Think-Pad (IBM) were used for computation.
      RESULTS: The median pCO (2) in VA blood was 50.5 and in UV blood 36.0 mmHg,
      respectively. Both distributions are normal. The AV difference amounted to 13.6
      mm Hg. The correlation between pCO (2), UA and the actual pH, UA is highly
      significant (r = -0.720, P << 0.0000). The correlation between pCO (2), UV and
      the pH, UA is still highly significant (r = -0.560, P<< 0.0000). Analysing only
      fetuses with an APGAR index of 9 or 10 after 1 min (N = 6304) reveals the
      important physiological influence of pCO (2), UV on actual pH, UA (r = -0.543, P
      << 0.0000). Moreover there exists an inverse and also highly significant
      dependency of pCO (2), UV and pO (2), UV in vigorous infants (P << 0.0000)
      indicating better fetal oxygenation; this cannot be explained by the weight of
      the placenta or other feto-placental measures. Taking into account maternal (N =
      101) respiration (arterial pH, pCO (2), pO (2)) during the last minutes of
      delivery leads to convincing evidence (P << 0.000) that pCO (2), UV is determined
      by maternal pCO (2) and thus by the breathing habits of the future mother (r =
      0.514 for pCO (2), UV and arterial pCO (2)). CONCLUSIONS: At the moment of
      delivery, where we usually determine actual pH and other parameters of the fetal
      ABB in order to control our obstetrical management, mother and fetus behave
      functionally as a unit; this fact deeply influences the predictive value of all
      fetal AB measurements (including BE, UA). This holds true also in fetal
      pathology. Maternal respiration turns out to be an important co-variable. In
      legal controversies the feto-maternal associations of blood gases and their
      implications must be considered carefully.

PMID- 15995942
TI  - [Fetal nephro-/uropathy: a retrospective analysis of 124 cases seen in the period
      from 1996 to 2002].
AB  - BACKGROUND: The embryological development of the kidneys and the urinary tract
      follows a complex choreography. Disorders are quite common. The incidence of
      disorders amounts to 0.3 - 0.8 % of live-born infants. In addition, several
      chromosomal anomalies are combined with renal malformations. The poor prognosis
      of some of these diseases is reflected in a perinatal mortality of 6.3 %.
      PATIENTS AND METHODS: Retrospectively 124 cases with fetal nephro-/uropathy
      detected by prenatal ultrasonography between 1996 and 2002 were analyzed.
      Features of hypo-dysplastic kidneys (uni- or bilateral) were seen in 21 cases.
      Multicystic kidney disease (uni- or bilateral) existed in 40 fetuses. In some
      cases of multicystic or dysplastic kidney diseases, extrarenal malformations were
      combined. 21 fetuses suffered from autosomal recessive polycystic kidney disease.
      18 male unborns showed the typical picture of intravesical obstruction due to
      posterior uretheral valves. The prune belly syndrome was seen 4 times.
      Hydronephrotic kidneys with more than 5 mm pelvic dilatation were detected in 13
      cases. Renal agenesis led to a lethal outcome perinatally in 5 cases. One child
      died of bilateral thrombosis of renal artery and venous system. RESULTS: The high
      incidence of diseases with a poor prognosis accounts for the high mortality of
      50.8 % (intrauterine or postnatal death, induced abortion). Such a fatal outcome
      was observed in autosomal recessive polycystic kidney disease, bilateral
      multicystic dysplastic kidney disease, bilateral renal dysplasia combined with
      severe extrarenal malformations, intravesical obstruction, renal agenesis and
      bilateral thrombosis of the renal vessels. Only 60 children survived. Of these 26
      needed urological surgery. 15 suffered from progressive renal insufficiency.
      During a follow-up of 8 - 58 months only 44 exhibited a normal renal function.
      CONCLUSIONS: Such complex renal and urological diseases in the fetus require an
      interdisciplinary management of the pregnancy.

PMID- 15995943
TI  - [Triploidy: prompt diagnosis based on typical clinical signs in a live-born
      extremely low birth-weight infant].
AB  - A child with complete triploidy is rarely born alive. However, owing to the
      advances in perinatal medicine even extremely immature preterm infants receive
      full support in the delivery room and are admitted to the neonatal ICU.
      Consequently, the clinician may also have to consider the diagnosis of triploidy
      when faced with a dysmorphic extremely preterm infant. We report here the
      smallest described live born girl of 25 + 5 weeks of gestational age with typical
      clinical findings of complete triploidy phenotype II. The aim of the case report
      is to make the neonatologist aware of this syndrome using photographs of this
      case as well as discussing the literature available. Prompt clinical diagnosis
      confirmed by chromosome analysis helps doctors and parents with the decision
      whether to continue promising or to limit futile life support measures.

PMID- 15995944
TI  - [Trauma during pregnancy].
AB  - In the past 60 years trauma has become the most important cause of morbidity and
      mortality in pregnancy. Motor vehicle accidents are the most common cause of
      abdominal trauma and lead to the highest mortality. The typical anatomical and
      physiological changes occurring during pregnancy demand a specific resuscitation
      procedure in which stabilization of the mother hemodynamically has to be done
      first. During the secondary survey the mother and fetus have to be examined
      thoroughly. The correct use of safety belts is an essential part of prevention.

PMID- 15995947
TI  - The need for another typhoid fever vaccine.

PMID- 15995948
TI  - The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic
      in 2 vaccine presentations.
AB  - BACKGROUND: M01ZH09 (Salmonella enterica serovar Typhi [Ty2 aroC(-) ssaV(-)] ZH9)
      is a live oral-dose typhoid vaccine candidate. M01ZH09 was rationally modified
      with 2 independently attenuating mutations, including a novel mutation in
      Salmonella pathogenicity island (SPI)-2. We demonstrate that M01ZH09, in a single
      oral dose, is well tolerated and prompts broad immune responses, regardless of
      whether prevaccination with a bicarbonate buffer is given. METHODS: Thirty-two
      healthy adult subjects were randomized and given 5x109 cfu of M01ZH09, with
      (presentation 1) or without (presentation 2) prevaccination with a bicarbonate
      buffer. Immunogenicity data included Salmonella Typhi lipopolysaccharide (LPS)
      specific immunoglobulin (Ig) A antibody-secreting cells (enzyme-linked immunospot
      [ELISPOT] assay), IgG serologic responses to Salmonella Typhi LPS, lymphocyte
      proliferation, and interferon (IFN)- gamma production. RESULTS: The vaccine was
      well tolerated; adverse events after vaccination were mild. No fever or prolonged
      vaccine shedding occurred. Immunogenicity data demonstrated that 88% and 93% of
      subjects who received presentation 1 and presentation 2, respectively, had a
      positive response by ELISPOT assay; 81% of subjects in both groups underwent IgG
      seroconversion on day 14. Both groups had similar cellular immune responses to
      presentation 1 and presentation 2; lymphocyte proliferation to Salmonella Typhi
      flagellin occurred in 63% and 67% of subjects, respectively, and 69% and 73% of
      subjects, respectively, had an increase in IFN- gamma production. CONCLUSION: The
      oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in a single
      oral dose, with and without prevaccination with a bicarbonate buffer. Field
      studies to demonstrate protective efficacy are planned.

PMID- 15995945
TI  - Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers
      susceptibility to autism and rigid-compulsive behaviors.
AB  - Autism is a spectrum of neurodevelopmental disorders with a primarily genetic
      etiology exhibiting deficits in (1) development of language and (2) social
      relationships and (3) patterns of repetitive, restricted behaviors or interests
      and resistance to change. Elevated platelet serotonin (5-HT) in 20%-25% of cases
      and efficacy of selective 5-HT reuptake inhibitors (SSRIs) in treating anxiety,
      depression, and repetitive behaviors points to the 5-HT transporter (5-HTT; SERT)
      as a strong candidate gene. Association studies involving the functional
      insertion/deletion polymorphism in the promoter (5-HTTLPR) and a polymorphism in
      intron 2 are inconclusive, possibly because of phenotypic heterogeneity.
      Nonetheless, mounting evidence for genetic linkage of autism to the chromosome
      17q11.2 region that harbors the SERT locus (SLC6A4) supports a genetic effect at
      or near this gene. We confirm recent reports of sex-biased genetic effects in 17q
      by showing highly significant linkage driven by families with only affected
      males. Association with common alleles fails to explain observed linkage;
      therefore, we hypothesized that preferential transmission of multiple alleles
      does explain it. From 120 families, most contributing to linkage at 17q11.2, we
      found four coding substitutions at highly conserved positions and 15 other
      variants in 5' noncoding and other intronic regions transmitted in families
      exhibiting increased rigid-compulsive behaviors. In the aggregate, these variants
      show significant linkage to and association with autism. Our data provide strong
      support for a collection of multiple, often rare, alleles at SLC6A4 as imposing
      risk of autism.

PMID- 15995949
TI  - Serum serotype-specific pneumococcal anticapsular immunoglobulin g concentrations
      after immunization with a 9-valent conjugate pneumococcal vaccine correlate with
      nasopharyngeal acquisition of pneumococcus.
AB  - BACKGROUND: Immunization with pneumococcal conjugate vaccines (PCVs) reduces
      nasopharyngeal colonization by Streptococcus pneumoniae. We attempted to
      correlate postvaccination serum serotype-specific pneumococcal anticapsular
      immunoglobulin (Ig) G concentrations with new acquisitions of vaccine-type (VT)
      serotypes and the VT-related serotype 6A. METHODS: A total of 132 day care center
      attendees aged 12-35 months received a 9-valent PCV (PnCRM9) and were followed
      for 2 years for new nasopharyngeal acquisitions of S. pneumoniae. A total of 132
      control subjects received a meningococcus type C conjugate vaccine. Serum
      serotype-specific pneumococcal anticapsular IgG concentrations were determined at
      1 month after complete immunization. RESULTS: A logistic regression model of the
      probability of having a new acquisition of S. pneumoniae (for serotypes 9V, 14,
      19F, and 23F) as a function of the IgG concentration showed a negative
      coefficient, indicating that higher IgG concentrations led to a decreasing
      probability of having a new acquisition, and achieved statistical significance
      for serotypes 14 and 19F. Similarly, a new acquisition of serotype 6A was shown
      to be significantly inversely related to the anti-6B IgG concentration. An effect
      of the IgG concentration on duration of carriage was not demonstrated.
      CONCLUSION: The magnitude of herd protection against S. pneumoniae provided by a
      PCV may depend on the magnitude of IgG concentrations.

PMID- 15995950
TI  - The influence of chronic illnesses on the incidence of invasive pneumococcal
      disease in adults.
AB  - Pneumococcal disease is more frequent and more deadly in persons with certain
      comorbidities. We used 1999 and 2000 data from the Active Bacterial Core
      surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine
      rates of invasive pneumococcal disease in healthy adults (> or =18 years old) and
      in adults with various high-risk conditions. The risks of invasive pneumococcal
      disease in persons with specific chronic illnesses was compared with that in
      healthy adults, controlling for age, race, and the other chronic illnesses.
      Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults,
      51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in
      adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among
      the high-risk groups evaluated, risk was highest in adults with solid cancer
      (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates
      increased with advancing age in adults with chronic lung disease, diabetes, and
      solid cancer. Black adults had higher incidence rates than white adults, both in
      healthy adults and in adults with chronic illnesses. These data support
      recommendations to provide pneumococcal vaccine to persons in these at-risk
      groups and underscore the need for better prevention strategies for
      immunocompromised persons.

PMID- 15995951
TI  - Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in
      adults: a longitudinal household study.
AB  - BACKGROUND: Natural immunity to Streptococcus pneumoniae is thought to be induced
      by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies
      of carriage of and immune responses to S. pneumoniae have been conducted using
      sophisticated immunological laboratory techniques. METHODS: We enrolled 121
      families with young children into this study. Nasopharyngeal (NP) swabs were
      collected monthly for 10 months from all family members and were cultured in a
      standard fashion. Cultured S. pneumoniae isolates were serotyped. At the
      beginning (month 0) and end (month 10) of the study, venous blood was collected
      from family members >18 years old. Serotype-specific antipolysaccharide
      immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin,
      pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA)
      were measured in paired serum samples. RESULTS: Levels of anticapsular IgG
      increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by
      an individual or family member. For serotype 14, a higher level of anticapsular
      IgG at the beginning of the study was associated with reduced odds of carriage (P
      = .006). There was a small (approximately 20%) but significant increase in titers
      of antibodies to PsaA and pneumolysin but no change in titers of antibody to
      PspA. CONCLUSIONS: Adults respond to NP carriage by mounting anticapsular and
      weak antiprotein antibody responses, and naturally induced anticapsular IgG can
      prevent carriage.

PMID- 15995952
TI  - Colonization of the rectum by Lactobacillus species and decreased risk of
      bacterial vaginosis.
AB  - Lactobacilli colonizing the rectum may be a reservoir for vaginal lactobacilli.
      In a cross-sectional study of 531 females, vaginal and rectal colonization by
      lactobacilli were assessed by culture methods. A subset of isolates was
      identified to the species level by use of whole-chromosomal DNA probes.
      Lactobacillus crispatus (16%), L. jensenii (10%), and L. gasseri (10%) were the
      prevalent lactobacilli colonizing the rectums of 290 females. Only 13 (9%) of 147
      females colonized by L. crispatus or L. jensenii vaginally and/or rectally had
      bacterial vaginosis (BV), compared with 12 (44%) of 27 females colonized by other
      H(2)O(2)-producing lactobacilli (P < .001). Cocolonization of the vagina and
      rectum by H(2)O(2)-producing lactobacilli was associated with the lowest
      prevalence of BV (5%), whereas females colonized only vaginally, only rectally,
      or at neither site had a successively increased risk of BV (P < .001).
      Lactobacillus species in the rectum may contribute to the maintenance of vaginal
      microflora.

PMID- 15995953
TI  - In tuberculous pleural effusions, activated neutrophils undergo apoptosis and
      acquire a dendritic cell-like phenotype.
AB  - Tuberculous pleuritis usually shows lymphocytic preponderance, but neutrophils
      are also present. Therefore, pleuritis is a good model for the study of
      neutrophil fate at sites of active Mycobacterium tuberculosis infection. We have
      previously demonstrated in vitro that M. tuberculosis-induced neutrophil
      apoptosis involves p38 mitogen protein kinase activation through Toll-like
      receptor 2. Herein, we demonstrate that, in tuberculous pleuritis, neutrophil
      apoptosis increases together with the expression of Toll-like receptor 2 and
      phosphorylated p38 (p-p38) kinase. In addition, receptors associated with
      activation/apoptotis (CD11b, CD64, tumor necrosis factor receptor, and Fas
      ligand) are up-regulated, together with a loss of CD16 expression. However,
      neutrophils express CD86, CD83, and major histocompatibility complex class II
      antigens, acquiring dendritic cell (DC) characteristics. Therefore, the cytokine
      milieu in the pleural space may influence signaling pathways on activated
      neutrophils, thereby inducing apoptosis and inhibiting their proinflammatory
      capacity, as well as allowing them acquire DC characteristics that influence the
      immune response.

PMID- 15995954
TI  - Nonmucoid Pseudomonas aeruginosa expresses alginate in the lungs of patients with
      cystic fibrosis and in a mouse model.
AB  - BACKGROUND: In patients with cystic fibrosis (CF), lung infection with mucoid
      Pseudomonas aeruginosa strains overexpressing the exopolysaccaride alginate is
      preceded by colonization with nonmucoid strains. We investigated the kinetics,
      impact of environmental signals, and genetics of P. aeruginosa alginate
      expression in a mouse model and in patients with CF. METHODS: Using indirect
      immunofluorescence, microarray technology and real-time reverse-transcription
      polymerase chain reaction, we assessed alginate gene expression during aerobic
      and anaerobic growth of the nonmucoid strain PAO1 in vitro, in a mouse lung
      infection model and in sputum specimens from patients with CF infected with
      nonmucoid or mucoid P. aeruginosa strains. RESULTS: Anaerobic conditions
      increased the transcription of alginate genes in vitro and in murine lungs within
      24 h. Alginate production by PAO1 in murine lungs and by nonmucoid P. aeruginosa
      strains in patients with CF was reversible after in vitro culture under aerobic
      conditions. A subpopulation of P. aeruginosa clones revealing stable alginate
      production was detected in murine lungs 2 weeks after infection. CONCLUSIONS:
      Anaerobiosis and lung infection rapidly induce alginate production by gene
      regulation in nonmucoid P. aeruginosa. This trait may contribute to early
      persistence, leading to chronic P. aeruginosa infection once stable mucoid
      strains are generated.

PMID- 15995955
TI  - Bacterial-population responses to drug-selective pressure: examination of
      garenoxacin's effect on Pseudomonas aeruginosa.
AB  - The emergence of resistance to antibiotics is a serious problem often related to
      suboptimal drug dosing; such suboptimal dosing results in the preferential
      killing of drug-susceptible microbial subpopulations, allowing amplification of
      drug-resistant microbial subpopulations. We determined the effect that
      fluctuating concentrations of quinolone drugs have on both the total population
      and the resistant subpopulation of Pseudomonas aeruginosa, by employing, over a
      48-h period, human pharmacokinetics and multiple regimens in an in vitro
      infection model. All data were simultaneously modeled by use of 3 parallel
      inhomogeneous differential equations. Model parameters were used to derive the
      minimal, or breakpoint, drug exposure necessary to suppress amplification of the
      resistant subpopulation. In a prospective-validation study, we found that a drug
      exposure near to but below the calculated breakpoint amplified the resistant
      subpopulation, whereas a drug exposure at the breakpoint suppressed it. This
      approach allows delineation of target drug exposures (area under the
      concentration/time curve for 24 h : minimal inhibitory concentration [AUC(24) :
      MIC] = 190) that will suppress amplification of the antibiotic-resistant
      subpopulation, thereby preserving the susceptibility of target pathogens.

PMID- 15995956
TI  - Urokinase-type plasminogen activator, an endogenous antibiotic.
AB  - Urokinase-type plasminogen activator (uPA) is a serine protease that not only
      displays fibrinolytic function but also modulates innate and adaptive immune
      responses. In the present study, we assessed whether uPA acts as an endogenous
      antibiotic. It has been demonstrated that uPA inhibits growth of Staphylococcus
      aureus both in vivo and in vitro. Importantly, the bactericidal properties of uPA
      are associated with the serine protease domain of the molecule but are not
      dependent on its plasminogen-activation potential and cannot be inhibited by
      plasminogen activator inhibitor type 1 (PAI-1). In a murine infection model, uPA
      treatment alleviated staphylococcal sepsis by inhibiting bacterial growth. To
      further evaluate the changes in uPA levels during the course of staphylococcal
      infection, total uPA and active uPA levels were analyzed in plasma and in kidney
      homogenates. Expression of total uPA was constant, but PAI-1 levels were
      dramatically increased in plasma and in kidney homogenates during the course of
      staphylococcal infection. After infection with staphylococci, the level of
      metabolically active uPA was unaltered in plasma but was significantly decreased
      in kidney homogenates. Active uPA levels were inversely related to PAI-1 levels
      and to bacterial loads in kidney homogenates. In conclusion, we report that uPA
      acts as an endogenous antibacterial substance that might constitute the first
      line of host defense against staphylococcal infection. The decreased active uPA
      levels in infected organs might be due to the dramatically increased PAI-1
      production during S. aureus infection.

PMID- 15995957
TI  - HIV superinfection.
AB  - Worldwide, 16 cases of HIV-1 superinfection in humans have been reported since
      2002. Superinfection is defined as the reinfection of an individual who already
      has an established infection with a heterologous HIV strain. Controversy exists
      surrounding superinfection, because it has implications concerning our
      understanding of worldwide HIV diversity, individual immunity and disease
      progression, and vaccine development. Here, we review the current understanding
      of HIV superinfection.

PMID- 15995958
TI  - Immunological response to highly active antiretroviral therapy in children with
      clinically stable HIV-1 infection.
AB  - We studied changes in 60 immunological parameters after the administration of
      highly active antiretroviral therapy (HAART) in 192 clinically stable
      antiretroviral drug-experienced HIV-1-infected children 4 months-17 years old.
      The studied immunological parameters included standard lymphocyte subsets and
      lymphocyte surface markers of maturation and activation. The most significant
      changes during the 48-week study period were seen for CD8(+),
      CD8(+)CD62L(+)CD45RA(+), CD8(+)CD38(+)HLA-DR(+), and CD4(+) T cell percentages (P
      < .0001 for all parameters). These changes suggest that significant decreases in
      the expression of activation markers and increases in the expression of naive
      markers in the CD8(+) T cell population may be related to better virologic
      control in these HIV-1-infected children, who had relatively stable immune
      function at the initiation of HAART. At week 44 of HAART, the major immunological
      parameters in these HIV-1-infected children moved from baseline values to about
      halfway to two-thirds of the way toward the values in healthy, uninfected
      children.

PMID- 15995959
TI  - HIV-1 Protease and reverse-transcriptase mutations: correlations with
      antiretroviral therapy in subtype B isolates and implications for drug-resistance
      surveillance.
AB  - Background. It is important, for drug-resistance surveillance, to identify human
      immunodeficiency virus type 1 (HIV-1) strains that have undergone antiretroviral
      drug selection.Methods. We compared the prevalence of protease and reverse
      transcriptase (RT) mutations in HIV-1 sequences from persons with and without
      previous treatment with protease inhibitors (PIs), nucleoside RT inhibitors
      (NRTIs), and nonnucleoside RT inhibitors (NNRTIs). Treatment-associated mutations
      in protease isolates from 5867 persons and RT isolates from 6247 persons were
      categorized by whether they were polymorphic (prevalence, >0.5%) in untreated
      individuals and whether they were established drug-resistance mutations. New
      methods were introduced to minimize misclassification from transmitted
      resistance, population stratification, sequencing artifacts, and multiple
      hypothesis testing.Results. Some 36 established and 24 additional nonpolymorphic
      protease mutations at 34 positions were related to PI treatment, 21 established
      and 22 additional nonpolymorphic RT mutations at 24 positions with NRTI
      treatment, and 15 established and 11 additional nonpolymorphic RT mutations at 15
      positions with NNRTI treatment. In addition, 11 PI-associated and 1 NRTI
      associated established mutations were polymorphic in viruses from untreated
      persons.Conclusions. Established drug-resistance mutations encompass only a
      subset of treatment-associated mutations; some of these are polymorphic in
      untreated persons. In contrast, nonpolymorphic treatment-associated mutations may
      be more sensitive and specific markers of transmitted HIV-1 drug resistance.

PMID- 15995960
TI  - Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of
      antiretroviral-naive individuals.
AB  - OBJECTIVE: We wished to characterize the epidemiological and clinical correlates
      of CXCR4-using human immunodeficiency virus type 1 (HIV-1) ("X4 variants") in a
      cross-sectional analysis of a large population of antiretroviral-naive
      individuals. METHODS: HIV-1 coreceptor use was determined in the last pretherapy
      plasma sample for 1191 individuals initiating triple-combination therapy in
      British Columbia, Canada. Baseline variables investigated included
      sociodemographic characteristics, plasma viral load (pVL), CD4 cell count, AIDS
      diagnosis, HIV-1 V3 loop sequence, and human CCR5 Delta 32 genotype. RESULTS:
      Individuals harboring X4 variants (n = 178 of 979 phenotyped samples; 18.2%)
      displayed a poorer baseline clinical profile than individuals harboring
      exclusively CCR5-using HIV-1 ("R5 variants") (median pVL, 175,000 vs. 120,000
      copies of HIV-1 RNA/mL [P = .0006]; median CD4 cell count, 110 vs. 290
      cells/mm(3) [P < .0001]). Individuals heterozygous for the CCR5 Delta 32 deletion
      (n = 128 of 967; 13.2%) were at 2.5 times higher risk of harboring X4 variants,
      compared with those without the deletion (multivariate P = .0005). The presence
      of basic amino acids at codon 11 and/or codon 25 of HIV-1 V3 (n = 109 of 955;
      11.4%) was associated with a 9.1 times higher risk of harboring X4 variants
      (multivariate P < .0001), regardless of CCR5 Delta 32 genotype. In multivariate
      analyses adjusting for baseline parameters, HIV-1 coreceptor use was not found to
      be a significant predictor of survival or treatment response. CONCLUSION:
      Baseline CD4 cell count, pVL, HIV-1 V3 sequence, and CCR5 Delta 32 genotype were
      the strongest determinants of CXCR4-using HIV-1 in this population. After
      adjustment for baseline parameters, the presence of X4 variants before initiation
      of highly active antiretroviral therapy was not independently associated with a
      poorer outcome of therapy.

PMID- 15995961
TI  - Molecular diversity of HIV in Albania.
AB  - Little information is available on circulating human immunodeficiency virus (HIV)
      subtypes and resistance to antiretroviral drugs in Albania. To fill this gap, we
      studied 72 plasma samples from HIV-infected individuals from throughout the
      country. Subtype classification and genotypic resistance analysis were performed
      on the HIV pol gene region. The analysis was successfully performed on 66 (91.6%)
      plasma samples and showed that 43 (65.2%) strains were non-B subtypes (mostly
      subtype A, as determined by analysis of pol gene sequences). No major mutations
      in the protease gene were found, whereas analysis of the reverse transcriptase
      gene revealed a few major mutations associated with resistance. In conclusion,
      non-B subtypes are predominant in Albania, and the prevalence of resistance to
      antiretroviral drugs is still low.

PMID- 15995962
TI  - The importance of recent infection with Mycobacterium tuberculosis in an area
      with high HIV prevalence: a long-term molecular epidemiological study in Northern
      Malawi.
AB  - BACKGROUND: The proportion of cases of tuberculosis due to recent infection can
      be estimated in long-term population-based studies using molecular techniques.
      Here, we present what is, to our knowledge, the first such study in an area with
      high human immunodeficiency virus (HIV) prevalence. METHODS: All patients with
      tuberculosis in Karonga District, Malawi, were interviewed. Isolates were
      genotyped using restriction-fragment-length polymorphism (RFLP) patterns. Strains
      were considered to be "clustered" if at least 1 other patient had an isolate with
      an identical pattern. RESULTS: RFLP results were available from 83% of culture
      positive patients from late 1995 to early 2003. When strains with <5 bands were
      excluded, 72% (682/948) were clustered. Maximum clustering was reached using a 4
      year window, with an estimated two-thirds of cases due to recent transmission.
      The proportion clustered decreased with age and varied by area of residence. In
      older adults, clustering was less common in men and more common in patients who
      were HIV positive (adjusted odds ratio, 5.1 [95% confidence interval, 2.1-12.6]).
      CONCLUSIONS: The proportion clustered found in the present study was among the
      highest in the world, suggesting high rates of recent transmission. The
      association with HIV infection in older adults may suggest that HIV has a greater
      impact on disease caused by recent transmission than on that caused by
      reactivation.

PMID- 15995963
TI  - Investigation of HIV in amniotic fluid from HIV-infected pregnant women at full
      term.
AB  - BACKGROUND: In the absence of interventions and breast-feeding, the in utero
      transmission rate of human immunodeficiency virus (HIV) is estimated to be 10%
      15%, and the role that amniotic fluid (AF) plays in this is unclear. OBJECTIVES:
      Levels of cytomegalovirus (CMV) in AF and levels of HIV-1 in AF, maternal blood,
      and fetal cord blood were assessed.Study design. We enrolled 23 HIV-1-positive
      women with healthy, singleton pregnancies who underwent elective cesarean section
      (CS) at full term. The Roche Amplicor HIV-1 Monitor test (version 1.5) was used
      for determination of maternal plasma VLs. The NASBA Nuclisens assay was used for
      determination of VLs in other samples. To determine the feasibility of detecting
      viral infections in AF, CMV polymerase chain reaction DNA extraction was
      performed on the AF samples by use of the QIAamp DNA kit. RESULTS: HIV-1 RNA was
      not detected in either AF or fetal cord blood. CMV was detected in 4 AF samples.
      Maternal CD4(+) T cell counts were 158-654 cells/mL (mean, 405 cells/mL). The
      maternal plasma VLs ranged from below detectable limits to 169,990 copies/mL
      (mean, 33,700 copies/mL). CONCLUSIONS: In the absence of medical complications
      and before labor, AF collected during elective CS from women who had received
      either zidovudine or nevirapine during late-stage pregnancy was free of HIV.

PMID- 15995964
TI  - Subtype C Is associated with increased vaginal shedding of HIV-1.
AB  - The prevalence of human immunodeficiency virus (HIV)-1-infected cells and HIV-1
      RNA levels in genital secretions and breast milk and the risk of mother-to-child
      transmission of HIV-1 were compared among subtypes A, C, and D in a Kenyan
      cohort. Pregnant women infected with subtype C were significantly more likely to
      shed HIV-1-infected vaginal cells than were those infected with subtype A or D
      (odds ratio [OR], 3.6 [95% confidence interval {CI}, 1.4-8.8]; P = .006). This
      relationship held after adjusting for age, CD4 cell count, and plasma HIV-1 RNA
      load (OR, 3.1 [95% CI, 1.1-8.6]; P = .03). These observations suggest that HIV-1
      subtype influences mucosal shedding of HIV-1.

PMID- 15995965
TI  - Normal functional capacity in circulating myeloid and plasmacytoid dendritic
      cells in patients with chronic hepatitis C.
AB  - Initial reports analyzing dendritic cell (DC) function in patients with hepatitis
      C virus (HCV) infection have been controversial. Here, we enumerate and
      characterize the function of circulating myeloid and plasmacytoid DCs. The
      results show lower percentages of myeloid DCs (0.62 vs. 0.83; P = .05) and
      plasmacytoid DCs (0.11 vs. 0.34; P = .004) in patients with chronic HCV infection
      than in healthy, non-HCV-infected individuals. Despite the lower numbers of
      circulating myeloid DCs present, no phenotypic or functional defects were
      identified. The lower percentage of plasmacytoid DCs resulted in decreased
      absolute interferon (IFN)-alpha production; however, when analyzed on a per-cell
      basis, plasmacytoid DCs from HCV-infected patients generated levels of IFN-alpha
      equivalent to those generated by DCs from healthy, non-HCV-infected individuals.
      Contrary to data from previous models (which attributed HCV pathogenesis to
      defects in the DC compartment), our data reveal functional DC subsets in patients
      with chronic HCV infection. These results are encouraging for DC-based HCV
      immunotherapy trials.

PMID- 15995966
TI  - Quantitation of DNA of polyomaviruses BK and JC in human kidneys.
AB  - BACKGROUND: Renal allograft recipients can be monitored for polyomavirus
      associated nephropathy (PVAN) using urine samples. Because virus in urine can be
      derived from the kidneys, ureter, or urinary bladder, we evaluated whether
      measurement of intrarenal concentrations of viral DNA might serve as a more
      reliable monitoring tool. METHODS: Real-time quantitative polymerase chain
      reaction was used to quantitate DNA of polyomaviruses BK (BKV) and JC (JCV) in
      renal tissue obtained from various clinical settings. RESULTS: Renal biopsy
      samples from 28 nonimmunosuppressed patients contained very low viral copy
      numbers. Minimally higher BKV loads (mean +/- SE, 3.4 +/- 1.7 copies/cell) were
      observed in 74 renal biopsy samples from renal allograft recipients with BKV
      viruria. The BKV DNA concentration was approximately 10-fold higher in renal
      allograft recipients with BKV viruria, but 58 (50.4%) of 115 renal biopsy samples
      tested negative for BKV DNA, reflecting the focal nature of infection. JCV DNA
      was found in only 2 renal biopsy samples. CONCLUSIONS: The BKV load is better
      measured in urine than in tissue, because a urine sample represents material from
      the entire kidney. An increase in the BKV load is usually not accompanied by a
      proportional increase in the JCV load, which indicates that these 2 related
      polyomaviruses are subject to different mechanisms regulating viral replication.

PMID- 15995967
TI  - Dengue Virus (DV) enhancing antibody activity in preillness plasma does not
      predict subsequent disease severity or viremia in secondary DV infection.
AB  - BACKGROUND: Dengue hemorrhagic fever, the most severe form of dengue illness, is
      associated with secondary dengue virus (DV) infection. Preexisting
      nonneutralizing antibodies to DV that enhance the infection of Fc gamma receptor
      bearing cells have been implicated in DV pathogenesis. METHODS: We conducted a
      prospective cohort study in Thai schoolchildren. Enhancing activity (EA) was
      measured as the percentage of DV-infected K562 cells, and viral titer (infected
      K562 cell supernatants) was measured in preillness plasma samples from children
      who subsequently had secondary DV2 or DV3 infection. RESULTS: Plaque-reduction
      neutralizing titers to the child's own DV2 or DV3 isolate were detected in 23 of
      32 and 8 of 27 of the preillness plasma samples, and EA was detected to a low
      passage Thai DV2 or DV3 in 31 of 32 and 26 of 27, respectively, of the samples.
      EA in undiluted preillness plasma did not correlate with subsequent disease
      severity or peak viremia levels in either secondary DV2 or DV3 infections.
      CONCLUSIONS: Preillness plasma enhances DV infection of K562 cells even in the
      presence of detectable neutralizing antibodies in LLC-MK2 cells. However, levels
      of preillness plasma EA of DV infection in K562 cells did not correlate with the
      clinical severity or viral burden of secondary DV infection.

PMID- 15995968
TI  - Differential induction of immunoglobulin G to Plasmodium falciparum variant
      surface antigens during the transmission season in Daraweesh, Sudan.
AB  - BACKGROUND: The acquisition of immunoglobulin (Ig) G to variant surface antigens
      (VSAs) seems important for the development of protective immunity against
      malaria. Unlike VSAs expressed by parasite isolates associated with uncomplicated
      malaria, VSAs expressed by parasite isolates associated with severe malaria
      (VSA(SM)) are frequently recognized by IgG. METHODS: We analyzed levels of anti
      VSA IgG in 57 individuals in Daraweesh, Sudan, before and after the transmission
      season. IgG responses to 79 Plasmodium falciparum isolates from children with
      defined malaria syndromes and exposed to high transmission in a different part of
      Africa were also analyzed. RESULTS: After the transmission season, individuals
      with malaria had an increase in IgG recognition to 25.8% (95% confidence interval
      [CI], 19.9%-31.7%) and a decrease in IgG recognition to 7.6% (95% CI, 4.4%-10.8%)
      of 79 parasite isolates, and individuals without malaria had an increase in IgG
      recognition to 8.1% (95% CI, 6.0%-10.2%) and a decrease in IgG recognition to
      11.9% (95% CI, 7.0%-16.8%) of 79 parasite isolates. Most newly acquired IgG
      responses were against parasite isolates expressing VSAs(SM) that are frequently
      recognized by IgG. CONCLUSIONS: Anti-VSA IgG levels decrease in the absence of
      infection, and an episode of clinical malaria induces IgG against a range of
      VSAs, particularly VSAs(SM).

PMID- 15995969
TI  - Nutritional status and serum cytokine profiles in children, adolescents, and
      young adults with Schistosoma japonicum-associated hepatic fibrosis, in Leyte,
      Philippines.
AB  - In a cross-sectional study of 641 Schistosoma japonicum-infected individuals in
      Leyte, Philippines, who were 7-30 years old, we determined the grade of hepatic
      fibrosis (HF) by ultrasound and used anthropometric measurements and hemoglobin
      levels to assess nutritional status. Serum levels of interleukin (IL)-1, IL-6,
      and IL-10; tumor-necrosis factor (TNF)-alpha; soluble TNF- alpha receptor I; and
      C-reactive protein (CRP) were measured to examine the association between these
      markers of inflammation and HF grade. HF was present in 8.9% of the cohort; the
      majority of cases were mild (grade I), and severe (grade II or grade III) cases
      occurred only in male individuals. Compared with individuals without HF, those
      with severe HF--and, to a lesser degree, those with mild HF--had a significantly
      lower body-mass index (BMI) and BMI z-score, a higher prevalence of anemia, and a
      higher level of CRP and were more likely to produce IL-6; furthermore, those with
      severe HF had a significantly higher level of IL-1, compared with those either
      without HF or with mild HF. These findings suggest that even mild HF is
      associated with nutritional morbidity and underscore the importance of early
      recognition and treatment. In addition, our data are consistent with the
      hypothesis that, by systemically increasing the levels of the proinflammatory
      cytokines IL-1 and IL-6, HF causes undernutrition and anemia.

PMID- 15995970
TI  - Bacille Calmette-Guerin inoculation induces chronic activation of peripheral and
      brain indoleamine 2,3-dioxygenase in mice.
AB  - BACKGROUND: Activation of the indoleamine 2,3-dioxygenase (IDO) enzyme and the
      resulting decrease in plasma tryptophan (TRP) levels appears to be a crucial link
      in the relationship between cytokines and depression. We aimed to develop an
      experimental model of chronic IDO activation based on bacille Calmette-Guerin
      (BCG) infection that elicits a robust increase in levels of interferon (IFN)-
      gamma, a key cytokine in the activation of IDO. METHODS: Mice were inoculated
      intraperitoneally with BCG (10(7) cfu/mouse). Lung and brain IDO activity was
      measured over time, together with plasma levels of TRP and IFN- gamma. RESULTS:
      BCG induced, over the course of several weeks, a chronic increase in serum IFN-
      gamma levels that was associated with a sustained enhancement of lung and brain
      IDO activity and with decreases in peripheral (serum and lungs) and brain
      concentrations of TRP, with different time courses between tissues. CONCLUSIONS:
      The model of BCG-induced IDO activation will be useful for the study of the
      consequences of peripheral immune activation in the brain and the role of TRP
      metabolism in cytokine-induced mood alteration.

PMID- 15995971
TI  - Appropriate use of nevirapine for long-term therapy.

PMID- 15995974
TI  - Postmortem brain smear assessment of fatal malaria.

PMID- 15995975
TI  - Isolated central nervous system blast crisis in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia is a myeloproliferative disorder characterized by the
      presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is
      a rare event. Imatinib mesylate has become the treatment of choice, especially
      for patients for whom allogenic stem cell transplantation is not an option.
      Imatinib produces complete cytogenetic responses in excess of 80%. However, the
      penetration of the drug and its metabolites into the CNS (Central Nervous System)
      is poor. Hence for patients who are on prolonged imatinib therapy and continue to
      have complete cytogenetic responses, the central nervous system may become a
      sanctuary site. We report a patient who had a complete hematologic and
      cytogenetic response and presented with headache and vomiting. The MRI showed
      meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive
      for blasts. He was started on cranial radiotherapy and triple intrathecal
      chemotherapy. He showed good symptomatic improvement and cleared the blasts in
      the CSF. At the end of radiation, he was in complete hematological remission but
      had 50% marrow metaphases positive for Philadelphia chromosome. As he did not
      have a matched sibling donor, the dose of imatinib was increased to 600 mg daily.
      He continues to be in complete hematologic remission at the time of this report.

PMID- 15995977
TI  - Xanthohumol induces apoptosis in cultured 40-16 human colon cancer cells by
      activation of the death receptor- and mitochondrial pathway.
AB  - Xanthohumol (XN) is one of the major prenylflavonoids found in hop cones (Humulus
      lupulus L.). In this study, we investigated the cell growth inhibitory potential
      of XN on cultured human colon cancer cells. Cell proliferation was measured by
      sulforhodamine B staining. Poly(ADP-ribose)polymerase (PARP) cleavage, activation
      of caspases-3, -7, -8, and -9, and Bcl-2 family protein expression were detected
      by Western blot analyses. XN significantly reduced proliferation of the HCT 116
      derived colon cancer cell line 40--16. Half-maximal inhibitory concentrations
      decreased from 4.1 microM after 24 h treatment to 3.6 and 2.6 microM after 48 and
      72 h incubation, respectively. Treatment with 15 microM XN for 48 h and with 5
      microM for 72 h led to the detection of the cleaved 89 kDa fragment of 116 kDa
      PARP as an indication of apoptosis induction. Concomitantly, we observed
      activation and cleavage of the effector caspases-3 and -7, induced by activation
      of the initiator caspases -8 and -9. Expression of anti-apoptotic Bcl-2 was down
      regulated when the cells were treated with XN for 48--72 h. We conclude that
      induction of apoptosis by downregulation of Bcl-2 and activation of the caspase
      cascade may contribute to the chemopreventive or therapeutic potential of XN.

PMID- 15995978
TI  - Enantiomeric analysis of baclofen analogs by capillary zone electrophoresis,
      using highly sulfated cyclodextrins: Inclusion ionization constant pKa
      determination.
AB  - Using cyclodextrin-capillary zone electrophoresis (CD-CZE), baseline separation
      of baclofen phaclofen, saclofen, and hydroxy-saclofen, potent gamma-aminobutyric
      acid(B) (GABA(B)) agonist or antagonists was achieved. A method for the
      enantioresolution of those analogs of GABA was developed using anionic
      cyclodextrins (highly sulfated CD or highly S-CD) as chiral selectors and
      capillaries dynamically coated with polyethylene oxide (PEO). With charged CDs we
      observed good resolutions due to the large electrophoretic mobility of these
      chiral selectors opposite to the mobility of the solutes. The highly S-alpha-CD
      and S-beta-CD were found to be complementary and the most effective complexing
      agent, allowing good enantiomeric resolution in short runtimes. The complete
      resolution was obtained using 25 mM phosphate buffer at pH 2.5 containing 3% w/v
      of highly S-alpha-CD or S-beta-CD at 25 degrees C with an applied field of 0.30
      kV/cm. The apparent binding constants of the inclusion complexes were evaluated
      and the migration order was determined. A comparison was possible to investigate
      the importance of the anionic group of the molecules in the separations. The
      pK(a) values were determined for all four compounds in order to explain relative
      electrophoretic migration of the solutes.

PMID- 15995979
TI  - Pulsed-field gel electrophoresis to study the diversity of whole-genome
      organization in the genus Ochrobactrum.
AB  - The alpha-proteobacterial genus Ochrobactrum groups together organisms that
      display varied life-styles, such as free-living bacteria, members of rhizosphere
      and soil, nitrogen-fixing bacteria in plant nodules, xenobiotic-degrading
      bacteria, colonizers of nematodes and insects, and opportunistic human pathogens.
      The genomes of nine strains of Ochrobactrum anthropi and eight strains of
      Ochrobactrum intermedium were analyzed by pulsed-field gel electrophoresis of the
      whole genome and of I-CeuI digestion fragments. All isolates and type strains of
      O. anthropi and O. intermedium possessed two high-molecular-weight circular
      replicons identified as two independent chromosomes on the basis of 16S rDNA
      hybridization. The genome of the type strain of Ochrobactrum tritici,
      Ochrobactrum grignonense, and Ochrobactrum gallinifaecis also contained two
      circular chromosomes. The megaplasmid content was highly variable even among
      strains in the same species, leading to whole-genome sizes that ranged from 5.060
      to 8.300 Mbp and from 4.690 to 7.680 Mbp for O. anthropi and O. intermedium,
      respectively. This exceptional level of genomic diversity could be related to the
      adaptability of Ochrobactrum spp. to various ecological niches.

PMID- 15995980
TI  - Rapid determination of aniline metabolites of chlorpropham in potatoes by
      micellar electrokinetic chromatography using negative-charged mixed micelles and
      laser-induced fluorescence detection.
AB  - A rapid, reliable method has been developed for the multi-residue analysis of
      aniline metabolites of chlorpropham in potato samples. The method involves the
      precolumn derivatization of aniline metabolites with 5-(4,6-dichloro-s-triazin-2
      ylamino) fluorescein (DTAF) and their subsequent separation and determination by
      micellar electrokinetic capillary chromatography with laser-induced fluorescence
      detection (MEKC-LIF). The optimum procedure includes a derivatization step of the
      aniline metabolites (3-chloroaniline, 3-chloro-4-hydroxyaniline and 3-chloro-4
      methoxyaniline) at 40 degrees C for 40 min and a 5-fold dilution prior to MEKC
      analysis, which is conducted within about 7 min using negative-charged mixed
      micelles (SDS/Triton X-100) in the running buffer. Under these conditions, the
      DTAF-anilines were readily detected at 0.3-3.1 microg/L level with a precision of
      4.8-6.4%. These results indicate that negative-charged mixed surfactant MEKC-LIF
      is useful as a selective, rapid, and sensitive tool for the determination of
      these anilines and surpasses other electrophoretic alternatives based on the use
      of fluorescein-isothiocyanate (FITC) as label reagent. Finally, the potato matrix
      showed no significant effects on the derivatization and determination of these
      analytes, since the analytical figures of merit for the real samples were similar
      to those obtained in aqueous solutions, and the average recovery at fortification
      levels of 10-250 microg/kg was over 97%.

PMID- 15995981
TI  - Microchip capillary electrophoresis with a cellulose-DNA-modified screen-printed
      electrode for the analysis of neurotransmitters.
AB  - A microfluidic chip based on capillary electrophoresis coupled with a cellulose
      single-stranded DNA (cellulose-ssDNA) modified electrode was used for the
      simultaneous analysis of dopamine (DA), norepinephrine (NE), 3,4-dihydroxy-L
      phenylalanine (L-DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), and ascorbic acid
      (AA). The modification of the electrode improved the electrophoretic analysis
      performance by lowering the detection potential and enhancing the signal-to-noise
      characteristic without surface poisoning of the electrode. The sensitivity of the
      modified electrode was about 12 times higher than those of the bare ones. The
      test compounds were separated using a 62 mm long separation channel at the
      separation field strength of +200 V/cm within 220 s in a 10 mM phosphate buffer
      (pH 7.4). The most favorable potential for the amperometric detection was 0.7 V
      (vs. Ag/AgCl). A reproducible response (relative standard deviation of 1.3, 1.3,
      2.1, 3.1, 3.4% for DA, NE, L-DOPA, DOPAC, and AA, respectively, for n = 9) for
      repetitive sample injections reflected the negligible electrode fouling at the
      cellulose-ssDNA modified electrode. Square-wave voltammetric analyses reflected
      the sensitivities of the modified electrode for DA, NE, L-DOPA, DOPAC, and AA
      which were 1.78, 0.82, 0.69, 2.45, and 1.23 nC/microM with detection limits of
      0.032, 0.93, 1.13, 0.31, and 0.62 microM, respectively. The applicability of this
      microsystem to real sample analysis was demonstrated.

PMID- 15995982
TI  - Capillary electrophoresis of polycationic poly(amidoamine) dendrimers.
AB  - Generation 2 to generation 5 poly(amidoamine) (PAMAM) dendrimers having different
      terminal functionalities were analyzed by capillary electrophoresis (CE).
      Polyacrylamide gel electrophoresis was also used to assess the composition of the
      individual generations for comparison with the CE results. Separation of PAMAMs
      can be accomplished by either using uncoated silica or silanized silica
      capillaries, although reproducibility is poor using the uncoated silica
      capillary. To improve run-to-run reproducibility, silanized capillary was used
      and various internal standards were also tested. Relative and normalized
      migration times of primary amine terminated PAMAM dendrimers were then determined
      using 2,3-diaminopyridine (2,3-DAP) as an internal standard. Using silanized
      capillaries and internal standards, the relative and normalized migration times
      are fully reproducible and comparable between runs. Apparent dimensionless
      electrophoretic mobilities were determined and the results were compared to
      theoretical calculations. It is concluded that for PAMAMs a complex separation
      mechanism has to be considered in CE, where the movement of the ions is due to
      the electric field, but the separation is rather the consequence of the
      adsorption/desorption equilibria on the capillary wall ("electrokinetic capillary
      chromatography"). The described method may be used for quality control and may
      serve as an effective technique to analyze polycationic PAMAM dendrimers and
      their derivatives with different surface modifications.

PMID- 15995984
TI  - Proteolytic processing of the peanut allergen Ara h 3.
AB  - The allergen Ara h 3 has been purified recently from peanuts. In contrast to
      recombinant Ara h 3, a 60 kDa single-chain polypeptide, the allergen isolated
      from its native source is extensively proteolytically processed. The
      characteristic proteolytic processing for 11S plant storage proteins of the
      glycinin family is observed for Ara h 3 yielding an acidic and a basic subunit,
      bound by a disulfide bridge. In addition to this, proteolytic truncation is
      observed for the acidic subunit but not for the basic subunit of Ara h 3. A
      series of Ara h 3 polypeptides ranging from 13-45 kDa was separated by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and each band was
      digested by trypsin. Peptides related to the bands were identified and a scheme
      positioning the different polypeptides in the Ara h 3 sequence has been
      constructed. Peptide analysis showed sequence heterogeneity at two positions
      indicating the presence of multiple genes encoding variant, but highly homologous
      Ara h 3 proteins. The pool of Ara h 3 polypeptides from its native source
      illustrated that allergen from the peanut is much more complex than the
      recombinant protein used for epitope mapping experiments. From several Ara h 3
      truncation products one or more immunoglobulin E (IgE) binding sites had been
      removed. Characterization of the allergenicity of Ara h 3 should therefore also
      include IgE-binding studies with peanut-derived Ara h 3, providing the high
      degree of variation in the Ara h 3 protein structure, as this is what peanut
      allergic individuals are confronted with.

PMID- 15995983
TI  - Determination of tertiary amines based on pH junctions and field amplification in
      capillary electrophoresis with electrochemiluminescence detection.
AB  - A stacking approach based on pH junction and field amplification has been
      developed for determining amines by capillary electrophoresis (CE) with
      electrochemiluminescence (ECL) detection. A two-electrode configuration was
      employed with an indium/tin oxide-coated glass as a working electrode and a
      platinum wire as a pseudoreference electrode. The ECL system also contains a flow
      cell (poly(dimethylsiloxane)-aluminum oxide) that was made from a mixture of
      Sylgard 184 silicone elastomer, a curing agent, and aluminum oxide. In order to
      improve the sensitivity of the present CE-ECL system using tris(2,2'-bipyridyl)
      ruthenium(II) (Ru(bpy)(3) (2+)), a stacking approach based on pH junctions and
      field amplification has been tested for the analysis of triethylamine (TEA),
      tripropylamine (TPA), and tributylamine (TBA). Once amines (cations) prepared in
      citric acid solution (pH < 4.0) migrate towards the background electrolyte (15 mM
      sodium borate at pH 8.0), they slow down and are stacked at the boundary as a
      result of deprotonation and decreases in the electric field. By applying
      hydrodynamic injection of the sample for 60 s, this method provides the
      concentration limits of detection (signal-to-noise ratio = 3) of 24, 20, and 32
      nM for TEA, TPA, and TBA, respectively. The results indicate that the stacking CE
      ECL system is better than CE-ECL systems using a two-electrode configuration and
      comparable to those using a three-electrode configuration. The potential
      applicability of the new and low-cost CE-ECL system has been demonstrated by the
      determination of 1.0 microM lidocaine, a local anesthetic drug, in urine without
      any tedious sample preparation.

PMID- 15995985
TI  - Distribution of conjugated linoleic acid in total and subcellular fractions from
      normal and cancerous parts of human testes.
AB  - The objective of the present study was to examine differences in the fatty acid
      composition of subcellular fractions from normal and cancerous parts of human
      testes. The conjugated linoleic acid (CLA) content was significantly higher in
      total testicular carcinoma (TC), but significantly lower in the mitochondrial
      fraction of TC in comparison to normal testicular tissue. The subcellular
      distribution pattern of CLA was similar to that of monounsaturated fatty acids,
      but different to that of 18:2n-6 (linoleic acid), underlining the different
      physiological properties of CLA and 18 : 2n-6. Because polyunsaturated fatty
      acids (PUFAs) have been suggested to have an effect on cancer risk and previous
      research has found that CLA inhibits the metabolism of 18 : 2n-6 into 20 : 4n-6,
      the contents of n-6 and n-3 PUFAs were determined. Significant differences were
      observed for 18 : 2n-6, 18 : 3n-3, 20 : 5n-3, and 22 : 6n-3, with 18 : 2n-6, 18 :
      3n-3, and 20 : 5n-3 contents being higher and 22 : 6n-3 content being lower in TC
      than in normal testicular tissue. These results indicate a changed availability
      of substrates for the cyclooxygenase (COX) or lipooxygenase (LOX) pathways
      generating eicosanoids. Although not statistically significant, the reduced
      content of 20 : 4n-6 shown in this study might be due to an increased metabolism
      of this fatty acid into eicosanoids.

PMID- 15995987
TI  - Elucidation of the mechanism of the 1,6-cuprate addition to acceptor-substituted
      enymes through 13C kinetic isotope effects: experimental and theoretical studies.

PMID- 15995986
TI  - Effects of the insoluble fiber derived from Passiflora edulis seed on plasma and
      hepatic lipids and fecal output.
AB  - The influence of the insoluble fiber-rich fraction (FRF) prepared from defatted
      Passiflora edulis seed, a potential fiber source, on plasma and hepatic lipids
      and fecal output were investigated in hamsters fed a hypercholesterolemic diet
      containing 5% insoluble FRF. The results showed that the consumption of insoluble
      FRF diet relative to cellulose diet could effectively (P < 0.05) decrease the
      levels of serum triglyceride, serum total cholesterol, and liver cholesterol, and
      increase (P < 0.05) the levels of total lipids, cholesterol, and bile acids in
      feces. The consumption of insoluble FRF also increased (P < 0.05) the fecal bulk
      and moisture. The marked cholesterol- and lipid-lowering effects of insoluble FRF
      might be partly attributed to its ability to enhance the excretion of lipids and
      bile acids via feces. Our results suggested that insoluble FRF could be a
      potential hypocholesterolemic ingredient for fiber-rich functional foods, but
      some further researches in humans may be needed to confirm its benefits.

PMID- 15995988
TI  - Polyethylenimine-grafted multiwalled carbon nanotubes for secure noncovalent
      immobilization and efficient delivery of DNA.

PMID- 15995989
TI  - Enhanced fidelity in mismatch extension by DNA polymerase through directed
      combinatorial enzyme design.

PMID- 15995990
TI  - Surface modification with orthogonal photosensitive silanes for sequential
      chemical lithography and site-selective particle deposition.

PMID- 15995991
TI  - The mechanism of chemical vapor deposition of cubic boron nitride films from
      fluorine-containing species.

PMID- 15995992
TI  - The structural and functional roles of rhodium(II)-rhodium(II) dimers in
      multinuclear ruthenium(II) complexes.

PMID- 15995993
TI  - Planar or perpendicular? Conformational preferences of pi-conjugated
      metalloporphyrin dimers and trimers in supramolecular tubular arrays.

PMID- 15995994
TI  - The introduction of pi-pi stacking moieties for fabricating stable micellar
      structure: formation and dynamics of disklike micelles.

PMID- 15995995
TI  - Switching of directions of bioelectrocatalytic currents and photocurrents at
      electrode surfaces by using hydrophobic magnetic nanoparticles.

PMID- 15995996
TI  - Self-assembly of semifluorinated janus-dendritic benzamides into bilayered
      pyramidal columns.

PMID- 15995997
TI  - Transfer of chirality from (-)-sparteine zinc(II) (meth)acrylate complexes to the
      main chains of their (meth)acrylate polymer derivatives.

PMID- 15995998
TI  - Dissociation of alkaliated alanine in the gas phase: the role of the metal
      cation.
AB  - The dissociation of prototypical metal-cationized amino acid complexes, namely,
      alkaliated alanine ([Ala+M]+, M+ = Li+, Na+, K+), was studied by energy-resolved
      tandem mass spectrometry with an ion-trap mass analyzer and by density functional
      theory. Dissociation leads to formation of fragment ions arising from the loss of
      small neutrals, such as H2O, CO, NH3, (CO+NH3), and the formation of Na+/K+. The
      order of appearance threshold voltages for different dissociation pathways
      determined experimentally is consistent with the order of critical energies
      (energy barriers) obtained theoretically, and this provides the necessary
      confidence in both experimental and theoretical results. Although not explicitly
      involved in the reaction, the alkali metal cation plays novel and important roles
      in the dissociation of alkaliated alanine. The metal cation not only catalyzes
      the dissociation (via the formation of loosely bound ion-molecule complexes and
      by stabilizing the more polar intermediates and transition structures), but also
      affects the dissociation mechanisms, as the cation can alter the shape of the
      potential energy surfaces. This compression/expansion of the potential energy
      surface as a function of the alkali metal cation is discussed in detail, and how
      this affects the competitive loss of H2O versus CO/(CO+NH3) from [Ala+M]+ is
      illustrated. The present study provides new insights into the origin of the
      competition between various dissociation channels of alkaliated amino acid
      complexes.

PMID- 15995999
TI  - From solution-phase to solid-phase enyne metathesis: crossover in the relative
      performance of two commonly used ruthenium pre-catalysts.
AB  - A crossover in the ability of two distinct ruthenium-based metathesis pre
      catalysts to effect the synthesis of dialkenylboronic esters in solution and on
      the solid-phase was observed. Specifically, while the Grubbs 2nd generation pre
      catalyst 3 affords a greater degree of conversion to product than the Hoveyda
      Grubbs pre-catalyst 2 in a solution-phase enyne-metathesis reaction, this trend
      is reversed in the solid-phase variant. Systematic investigation showed this
      trend to be general, regardless of variations in the homoallylic alcohol and
      alkynylboronic ester components of the reaction, as well as in the type of solid
      support employed. Experiments to determine a mechanistic hypothesis for this
      trend highlighted the significance of the ruthenium remaining bound to the
      substrate after metathetic rearrangement and found the presence of phosphine
      ligand to be detrimental to the success of the solid-phase reaction. Therefore,
      these results suggest an expanded role for phosphine-free pre-catalysts, such as
      2, in challenging solid-phase metathesis reactions.

PMID- 15996000
TI  - The microstructure of copper zinc oxide catalysts: bridging the materials gap.

PMID- 15996001
TI  - Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one
      dimensional (1)H and two-dimensional (1)H-(13)C NMR.
AB  - (1)H-NMR spectroscopy at 500 MHz was used to confirm that a previously
      unidentified singlet resonance at 3.14 ppm in the spectra of cerebrospinal fluid
      and plasma samples corresponds to dimethyl sulfone (DMSO(2)). A triple resonance
      inverse cryogenic NMR probe, with pre-amplifier and the RF-coils cooled to low
      temperature, was used to obtain an (1)H-(13)C HSQC spectrum of CSF containing 8
      microM (753 ng/ml) DMSO(2). The (1)H-(13)C correlation signal for DMSO(2) was
      assigned by comparison with the spectrum from an authentic reference sample. In
      plasma and CSF from healthy controls, the concentration of DMSO(2) ranged between
      0 and 25 micromol/l. The concentration of DMSO(2) in plasma from three of four
      patients with severe methionine adenosyltransferase I/III (MAT I/III) deficiency
      was about twice the maximum observed for controls. Thus, DMSO(2) occurs as a
      regular metabolite at low micromolar concentrations in cerebrospinal fluid and
      plasma. It derives from dietary sources, from intestinal bacterial metabolism and
      from human endogenous methanethiol metabolism.

PMID- 15996002
TI  - Impaired IGF-I signalling of hypertrophic hearts in the developmental phase of
      hypertension in genetically hypertensive rats.
AB  - Insulin-like growth factor-I (IGF-I) signalling is reported to contribute to the
      modulation of blood pressure and set survival and hypertrophic responses in
      cardiac tissue. However, whether IGF-I signalling normally acts in cardiac
      tissues of hypertensive rats is unknown. In this study, using spontaneously
      hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SPSHR),
      both with early blood pressure increases, and Wistar-Kyoto (WKY) rats as
      controls, we measured the hypertrophic and IGF-I signalling activity changes in
      rat hearts at 4, 6 and 12 weeks of age. Both SHR and SPSHR were found to have
      significantly increased blood pressures and ratios of heart- and left ventricle-
      to body weight at 12 weeks of age. However, IGF-IR and its downstream signalling,
      including the protein levels of PI3K and phosphorylated Akt, known to maintain
      physiological cardiac hypertrophy and cardiomyocyte survival, were downregulated.
      The results of dot blotting showed that cardiac mRNA levels of IGF-I in
      hypertensive rats were higher than those in controls starting from the age of 4
      weeks. This difference suggests the increased ligand IGF-I mRNA levels may be a
      compensatory response caused by the impaired IGF-I signalling. Moreover, enhanced
      cardiac cytosolic cytochrome-c, a mitochondria-dependent apoptotic pathway
      component, tended to occur in both hypertensive rats, although it did not reach a
      significant level. These findings indicate that impaired IGF-IR signalling occurs
      at early stages, and it may contribute, at least partially, to the development of
      hypertension and pathological cardiac hypertrophy and to cardiomyocyte apoptosis
      at later stages in SHR and SPSHR.

PMID- 15996003
TI  - Synthesis of 6-(3,5-dichlorobenzyl) derivatives as isosteric analogues of the HIV
      drug 6-(3,5-dimethylbenzyl)-1-(ethoxymethyl)-5-isopropyluracil (GCA-186).
AB  - The HIV-1 inhibitors described in this paper is closely related to 6-(3,5
      dimethylbenzyl)-1-(ethoxy methyl)-5-isopropyluracil (GCA-186) an anti-HIV-1 drug
      that is highly active against both wild type and mutated HIV-1 strains. The two
      methyl groups on the 6-benzyl moiety have been shown to improve the binding
      stability of the drug to the NNRTI-binding site in reverse transcriptase of drug
      mediated mutant HIV-1 viruses. The methyl groups are replaced with isosteric
      chloro-atoms to avoid metabolism due to the two methyl groups. However, the
      isosteric chloro derivatives show tenfold less activity against HIV-1 than their
      corresponding methyl derivatives. The synthesis and the antiviral activities of
      the corresponding 1-(allyloxy- and indanyloxy)methyl-6-(3,5-dichlorobenzyl)-5
      ethyluracil derivatives are also reported.

PMID- 15996004
TI  - Alkoxycarbonyloxyethyl ester prodrugs of FR900098 with improved in vivo
      antimalarial activity.
AB  - FR900098 represents a derivative of the new antimalarial drug fosmidomycin with
      enhanced activity. The mechanism of action is the inhibition of the 1-desoxy-D
      xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the
      mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with
      increased oral activity in mice infected with the rodent malaria parasite
      Plasmodium vinckei were obtained by masking the phosphonate moiety of FR900098 as
      alkoxycarbonyloxyethyl esters.

PMID- 15996005
TI  - Exploiting the carboxylate chemical shift to resolve degenerate resonances in
      spectra of 13C-labelled glycosaminoglycans.
AB  - Glycosaminoglycans (GAG) are important vertebrate extracellular matrix
      polysaccharides that comprise repeated units of an acidic and an N-acetylated
      sugar. The constituent acidic sugars are central to their biological functions,
      but have been largely inaccessible to NMR because the (1)H resonances overlap
      with those from other residues. Here, pulse sequences that address this failure
      are developed using (13)C-enriched oligosaccharides of the glycosaminoglycan,
      hyaluronan, as model systems. Two pulse sequences are presented that exploit the
      unique chemical shifts and scalar couplings present at the carboxylate moiety to
      filter out coherences from the N-acetylated sugars and produce simple spectra
      containing only resonances from the acidic sugars. The first sequence uses one
      bond couplings to correlate the carboxylate carbon with the adjacent carbon and
      its directly attached proton, while the second sequence exploits a long-range
      coupling to correlate the carboxylate carbon with the anomeric proton and carbon
      of the same residue. In addition, inclusion of an isotropic mixing block into
      these sequences allows resonances from the otherwise degenerate ring protons to
      be resolved. Spectra from the hyaluronan tetra- and hexasaccharides show that all
      glucuronic acid (GlcA) residues can be resolved from one another, allowing nuclei
      to be assigned in a sequence-specific manner. However, in some spectra,
      resonances are observed at positions not predicted by spin-operator analysis, and
      simulations reveal that these additional magnetisation transfers result from
      strong-coupling. These experiments represent a foundation from which new
      structural and biochemical information can be obtained in a sequence-specific
      manner for the acidic sugar residues in hyaluronan and other glycosaminoglycans.

PMID- 15996006
TI  - Context moderates illness-induced lifestyle disruptions across life domains: a
      test of the illness intrusiveness theoretical framework in six common cancers.
AB  - The illness intrusiveness theoretical framework maintains that illness-induced
      lifestyle disruptions compromise quality of life in chronic life-threatening
      conditions and that this effect is moderated by social, psychological, and
      contextual factors. Considerable evidence indicates that lifestyle disruptions
      compromise quality of life in cancer and other diseases and that the effects
      differ across life domains. The hypothesis that contextual factors (e.g. age,
      education, income, stressful life events) moderate these effects has not been
      tested extensively. We investigated whether age, income, education, and/or recent
      stressful life events modify the experience of illness intrusiveness across three
      central life domains (Relationships and Personal Development, Intimacy, and
      Instrumental life) in six common cancers. A sample of 656 cancer outpatients with
      one of six common cancers (breast, prostate, lymphoma, lung, head and neck, and
      gastrointestinal, all n's>100) completed the Illness Intrusiveness Ratings Scale
      while awaiting follow-up appointments with an oncologist. Results indicated
      statistically significant (all p's<0.05) interactions involving each of the
      hypothesized moderator variables and the Life Domain factor. In each case,
      greatest divergence was evident when illness intrusiveness involved instrumental
      life domains (e.g. work, finances, health, and active recreation). The findings
      substantiate the illness intrusiveness theoretical framework and support its
      relevance for people with cancer. The psychosocial impact of chronic life
      threatening disease differs across life domains and depends on the context in
      which it is experienced.

PMID- 15996007
TI  - Proteomic analysis of protein expression profiles during Caenorhabditis elegans
      development using two-dimensional difference gel electrophoresis.
AB  - Coordinated protein expression is critical for the normal execution of animal
      development. To obtain overall proteome profiles during animal development, a
      small free-living soil nematode, Caenorhabditis elegans, was used as a model and
      the developmental changes of protein expressions were analyzed using two
      dimensional difference gel electrophoresis. Protein samples from six
      developmental stages were prelabeled with fluorescent cyanine dyes and separated
      on two-dimensional electrophoresis gels. Image-to-image analysis of protein
      abundances together with protein identification by peptide mass fingerprinting
      yielded the developmental expression profiles of 231 spots representing 165
      proteins. About a quarter of the identified proteins were expressed in multiple
      spots with different isoelectric points, suggesting a certain proportion of
      proteins were variously modified. This notion was supported by the observation
      that about a third of the multispot proteins were stained positive for a
      phosphoprotein specific dye. While a fairly large number of the proteins showed
      little alteration in their expression profiles during development, about 40
      proteins were found to be significantly either up- or down-regulated between the
      embryos and newly hatched L1 larvae. Down-regulated proteins included those
      related to the cell cycle such as MCM-7, PCN-1, and the mitotic checkpoint
      protein, while up-regulated proteins included structural proteins such as actins,
      LEV-11, DIM-1, VAB-21, metabolic enzymes such as ATP synthase, ALH-12, fluctose
      1,6-bisphosphate aldolase and GPD-3, and galectins. A standard proteome map was
      obtained where the defects in the mutations of developmental genes and the
      effects of reagents on the development in C. elegans were analyzed.

PMID- 15996008
TI  - Proteomic signatures for histological types of lung cancer.
AB  - We performed proteomic studies on lung cancer cells to elucidate the mechanisms
      that determine histological phenotype. Thirty lung cancer cell lines with three
      different histological backgrounds (squamous cell carcinoma, small cell lung
      carcinoma and adenocarcinoma) were subjected to two-dimensional difference gel
      electrophoresis (2-D DIGE) and grouped by multivariate analyses on the basis of
      their protein expression profiles. 2-D DIGE achieves more accurate quantification
      of protein expression by using highly sensitive fluorescence dyes to label the
      cysteine residues of proteins prior to two-dimensional polyacrylamide gel
      electrophoresis. We found that hierarchical clustering analysis and principal
      component analysis divided the cell lines according to their original histology.
      Spot ranking analysis using a support vector machine algorithm and unsupervised
      classification methods identified 32 protein spots essential for the
      classification. The proteins corresponding to the spots were identified by mass
      spectrometry. Next, lung cancer cells isolated from tumor tissue by laser
      microdissection were classified on the basis of the expression pattern of these
      32 protein spots. Based on the expression profile of the 32 spots, the isolated
      cancer cells were categorized into three histological groups: the squamous cell
      carcinoma group, the adenocarcinoma group, and a group of carcinomas with other
      histological types. In conclusion, our results demonstrate the utility of
      quantitative proteomic analysis for molecular diagnosis and classification of
      lung cancer cells.

PMID- 15996009
TI  - Increased lungkine and chitinase levels in allergic airway inflammation: a
      proteomics approach.
AB  - Asthma is a chronic inflammatory disease characterized by pulmonary eosinophilia
      and airway hyperresponsiveness. Mechanisms underlying the pathogenesis of asthma
      are still not fully understood. The present study investigated alterations in
      global protein expression in bronchoalveolar lavage fluid in allergic airway
      inflammation using a proteomics approach. BALB/c mice sensitized and challenged
      with ovalbumin developed airway eosinophilia, mucus hypersecretion, elevation of
      immunoglobulin E, and airway hyperresponsiveness. Lavage fluid proteins from
      normal and asthmatic mice were resolved by two-dimensional gel electrophoresis,
      and identified by peptide mass fingerprinting matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. A total of 28 protein
      spots were significantly altered. Several of these proteins were undetectable or
      at very low levels in normal mice but were significantly increased in airway
      inflammation. These include lungkine, a recently described chemokine, a family of
      chitinases including Ym1, Ym2, and acidic mammalian chitinase, gob-5, a protein
      that mediates mucus secretion, and surfactant protein-D, a C-type lectin capable
      of modulating inflammatory responses. Overall, proteomics is a powerful tool in
      unraveling protein expression changes in allergic airway inflammation. The
      proteins identified in this study may be associated with the pathogenesis of
      allergic airway inflammation and may also be found useful as surrogate biomarkers
      for asthma.

PMID- 15996010
TI  - Identification of human nasal mucous proteins using proteomics.
AB  - The determination of possible biomarkers in nasal secretion of healthy subjects
      can have a role in early diagnosis of diseases such as rhinosinusitis. For this
      purpose, nasal lavage fluids (NLFs) from ten volunteers, collected before and
      after they had been submitted to nasal provocations, were investigated.
      Separation and analysis of proteins present in this complex matrix was performed
      using a capillary liquid chromatography-electrospray-quadrupole-time of flight
      mass spectrometry equipment. From among a total of 111 proteins found (89 known
      and two unknown proteins), 42 of which had never been previously described in
      this fluid, such as Deleted in Malignant Brain Tumors 1 isoform a precursors, and
      cytoskeletal proteins were identified with high statistical score. Three proteins
      of palate lung nasal epithelial clone (PLUNC) family: SPLUNC1, LPLUNC1, and
      LPLUNC2 were identified. Proteins involved in innate (27%) and acquired immunity
      (21%) systems were major components of NLF. Cellular (52% of all proteins
      identified) such as cytoskeletal (33%), functional (15%), and regulatory (4%)
      proteins, normally present in the nasal cavity, have also been identified. The
      proteomic approach presented here allowed us to identify the proteins involved in
      acquired and innate immune response in the nose against microbial infections and
      unclean inhaled air.

PMID- 15996011
TI  - A proteomics study of in vitro cyst germination and appressoria formation in
      Phytophthora infestans.
AB  - A proteomics study using two-dimensional gel electrophoresis (2-DE) and mass
      spectrometry was performed on Phytophthora infestans. Proteins from cysts,
      germinated cysts and appressoria grown in vitro were isolated and separated by 2
      DE. Statistical quantitative analysis of the protein spots from five independent
      experiments of each developmental stage revealed significant up-regulation of ten
      spots on gels from germinated cysts compared to cysts. Five spots were
      significantly up-regulated on gels from appressoria compared to germinated cysts
      and one of these up-regulated spots was not detectable on gels from cysts. In
      addition, one spot was significantly down-regulated and another spot not
      detectable on the gels from appressoria. The corresponding proteins to 13 of
      these spots were identified with high confidence using tandem mass spectrometry
      and database searches. The functions of the proteins that were up-regulated in
      germinated cysts and appressoria can be grouped into the following categories:
      protein synthesis (e.g. a DEAD box RNA helicase), amino acid metabolism, energy
      metabolism and reactive oxygen species scavenging. The spot not detected in
      appressoria was identified as the P. infestans crinkling- and necrosis-inducing
      protein CRN2. The identified proteins are most likely involved in the
      establishment of the infection of the host plant.

PMID- 15996012
TI  - Including mutations from conceptually translated expressed sequence tags into
      orthologous proteins improves the preliminary assignment of peptide mass
      fingerprints on non-model genomes.
AB  - In order to improve protein assignment from peptide mass fingerprints (PMF) in
      species with incompletely sequenced genomes, the genus-specific mutations deduced
      from Expressed sequence tag (EST) sequences were included in the complete reading
      frames of orthologous proteins, resulting in a new searchable in silico protein
      database. Using this method in tests on four plant species, the MOWSE score of at
      least 20% more proteins was improved compared to conventional approaches on
      crude, total proteins, for middle-sized EST projects. Larger contigs are
      assembled in more important EST projects and this improves the conventional
      assignment of the most abundant proteins. However, contigs from minor transcripts
      remain shorter and the assignment of less abundant proteins, such as those
      isolated following subcellular fractionment, is improved by searching orthologue
      EST conceptual chimeras with the PMF spectra. This strategy may be utilized as a
      tool to identify potential PMF matches that can be then verified by other
      experimental approaches (tandem mass spectrometry) to ensure the EST matched
      chimera identification is accurate.

PMID- 15996016
TI  - Quantitative analysis of the farnesyl transferase inhibitor lonafarnib
      (Sarasartrade mark, SCH66336) in human plasma using high-performance liquid
      chromatography coupled with tandem mass spectrometry.
AB  - Lonafarnib is a novel anticancer drug that inhibits farnesyl transferase. To
      assess its pharmacokinetic properties, we developed a sensitive and quantitative
      assay using liquid chromatography coupled with tandem mass spectrometry for the
      determination of lonafarnib levels in human plasma. Sample pretreatment consisted
      of the addition of an isotopically labeled internal standard and protein
      precipitation with acetonitrile using 100 microL plasma. Chromatographic
      separation was performed on an Inertsil ODS-3 analytical column (50 x 2.1 mm
      i.d., particle size 5 microm) with acetonitrile/water/formic acid (50:50:0.05,
      v/v/v) as the mobile phase, at a flow rate of 0.2 mL/min. The analytical run time
      was 8 min. An API365 triple quadrupole mass spectrometer was used for specific
      and sensitive detection. It was operated in the positive ion mode and multiple
      reaction monitoring was used for drug quantification. The method was validated
      using a concentration range of 2.5 to 2500 ng/mL lonafarnib. Validation of the
      assay was performed according to the most recent FDA guidelines for bioanalytical
      method validation and all results were within the requirements. The described
      method was successfully applied to support a clinical phase I trial with
      lonafarnib.

PMID- 15996017
TI  - Characterization of carbofuran photodegradation by-products by liquid
      chromatography/hybrid quadrupole time-of-flight mass spectrometry.
AB  - The structural elucidation of by-products arising from carbofuran
      photodegradation using a high-pressure UV lamp has been investigated by liquid
      chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS)
      employing a quadrupole time-of-flight mass spectrometer. Exact mass measurements
      of the [M + H]+ ions of the by-products and of product ions allowed the elemental
      formulae and related structures of seven photodegradation by-products (resulting,
      respectively, from photo-Fries rearrangement, hydroxylation of the benzene ring,
      oxidation of the 2,3-dihydrobenzofuran ring, cleavage of the carbamate group,
      hydrolysis of the ether group and the newly observed radical coupling and
      decarboxylation processes) to be determined confidently. Accurate mass
      measurements of product ions allowed ambiguities to be removed concerning neutral
      losses having the same nominal mass, namely CO and C2H4, allowing the
      fragmentation patterns to be rationalized.

PMID- 15996019
TI  - Antitumor efficacy of lidamycin on hepatoma and active moiety of its molecule.
AB  - AIM: To study the in vitro and in vivo antitumor effect of lidamycin (LDM) on
      hepatoma and the active moiety of its molecule. METHODS: MTT assay was used to
      determine the growth inhibition of human hepatoma BEL-7402 cells, SMMC-7721 cells
      and mouse hepatoma H22 cells. The in vivo therapeutic effects of lidamycin and
      mitomycin C were determined by transplantable hepatoma 22 (H22) in mice and human
      hepatoma BEL-7402 xenografts in athymic mice. RESULTS: In terms of IC(50) values,
      the cytotoxicity of LDM was 10 000-fold more potent than that of mitomycin C
      (MMC) and adriamycin (ADM) in human hepatoma BEL-7402 cells and SMMC-7721 cells.
      LDM molecule consists of two moieties, an aproprotein (LDP) and an enediyne
      chromophore (LDC). In terms of IC(50) values, the potency of LDC was similar to
      LDM. However, LDP was 10(5)-fold less potent than LDM and LDC to hepatoma cells.
      For mouse hepatoma H22 cells, the IC(50) value of LDM was 0.025 nmol/L. Given by
      single intravenous injection at doses of 0.1, 0.05 and 0.025 mg/kg, LDM markedly
      suppressed the growth of hepatoma 22 in mice by 84.7%, 71.6% and 61.8%,
      respectively. The therapeutic indexes (TI) of LDM and MMC were 15 and 2.5,
      respectively. By 2 iv. injections in two experiments, the growth inhibition rates
      by LDM at doses of 0.1, 0.05, 0.025, 0.00625 and 0.0125 mg/kg were 88.8-89.5%,
      81.1-82.5%, 71.2-74.9%, 52.3-59.575%, and 33.3-48.3%, respectively. In
      comparison, MMC at doses of 5, 2.5, and 1.25 mg/kg inhibited tumor growth by 69.7
      73.6%, 54.0-56.5%, and 31.5-52.2%, respectively. Moreover, in human hepatoma BEL
      7402 xenografts, the growth inhibition rates by LDM at doses of 0.05 mg/kg X2 and
      0.025 mg/kg X2 were 68.7% and 27.2%, respectively. However, MMC at the dose of
      1.25 mg/kg X2 showed an inhibition rate of 34.5%. The inhibition rate of tumor
      growth by LDM was higher than that by MMC at the tolerated dose. CONCLUSION: Both
      LDM and its chromophore LDC display extremely potent cytotoxicity to hepatoma
      cells. LDM shows a remarkable therapeutic efficacy against murine and human
      hepatomas in vivo.

PMID- 15996018
TI  - Factors affecting recurrence after surgery for Crohn's disease.
AB  - Although in Crohn's disease post-operative recurrence is common, the determinants
      of disease recurrence remain speculative. The aim of this study was to examine
      factors affecting post-operative recurrence of Crohn's disease. A Medline-based
      literature review was carried out. The following factors were investigated: age
      at onset of disease, sex, family history of Crohn's disease, smoking, duration of
      Crohn's disease before surgery, prophylactic medical treatment (corticosteroids,
      5-amino salicylic acid (5-ASA) and immunosuppressants), anatomical site of
      involvement, indication for surgery (perforating or non-perforating disease),
      length of resected bowel, anastomotic technique, presence of granuloma in the
      specimen, involvement of disease at the resection margin, blood transfusions and
      post-operative complications. Smoking significantly increases the risk of
      recurrence (risk is approximately twice as high), especially in women and heavy
      smokers. Quitting smoking reduces the post-operative recurrence rate. A number of
      studies have shown a higher risk when the duration of the disease before surgery
      was short. There were, however, different definitions of 'short' among the
      studies. Prophylactic corticosteroids therapy is not effective in reducing the
      post-operative recurrence. A number of randomized controlled trials offered
      evidence of the efficacy of 5-ASA (mesalazine) in reducing post-operative
      recurrence. Recently, the therapeutic efficacy of immunosuppressive drugs
      (azathioprine and 6-mercaptopurine) in the prevention of post-operative
      recurrence has been investigated and several studies have reported that these
      drugs might help prevent the recurrence. Further clinical trials would be
      necessary to evaluate the prophylactic efficacy of immunosuppressants. Several
      studies showed a higher recurrence rate in patients with perforating disease than
      in those with non-perforating disease. However, evidence for differing recurrence
      rates in perforating and non-perforating diseases is inconclusive. A number of
      retrospective studies reported that a stapled functional end-to-end anastomosis
      was associated with a lower recurrence rate compared with other types of
      anastomosis. However, prospective randomized studies would be necessary to draw a
      definite conclusion. Many studies found no difference in the recurrence rates
      between patients with radical resection and non-radical resection. Therefore,
      minimal surgery including strictureplasty has been justified in the management of
      Crohn's disease. In this review, the following factors do not seem to be
      predictive of post-operative recurrence: age at onset of disease, sex, family
      history of Crohn's disease, anatomical site of disease, length of resected bowel,
      presence of granuloma in the specimen, blood transfusions and post-operative
      complications. The most significant factor affecting post-operative recurrence of
      Crohn's disease is smoking. Smoking significantly increases the risk of
      recurrence. A short disease duration before surgery seems, albeit to a very minor
      degree, to be associated with a higher recurrence rate. 5-ASA has been shown with
      some degree of confidence to lead to a lower recurrence rate. The prophylactic
      efficacy of immunosuppressive drugs should be assessed in future. A wider
      anastomotic technique after resection may reduce the post-operative recurrence
      rate, though this should be investigated with prospective randomized controlled
      trials.

PMID- 15996020
TI  - Human scFv antibody fragments specific for hepatocellular carcinoma selected from
      a phage display library.
AB  - AIM: To identify the scFv antibody fragments specific for hepatocellular
      carcinoma by biopanning from a large human naive scFv phage display library.
      METHODS: A large human naive scFv phage library was used to search for the
      specific targets by biopanning with the hepatocellular carcinoma cell line HepG2
      for the positive-selecting and the normal liver cell line L02 for the counter
      selecting. After three rounds of biopanning, individual scFv phages binding
      selectively to HepG2 cells were picked out. PCR was carried out for
      identification of the clones containing scFv gene sequence. The specific scFv
      phages were selected by ELISA and flow cytometry. DNA sequences of positive
      clones were analyzed by using Applied Biosystem Automated DNA sequencers 3 730.
      The expression proteins of the specific scFv antibody fragments in E.coli HB2151
      were purified by the affinity chromatography and detected by SDS-PAGE, Western
      blot and ELISA. The biological effect of the soluble antibody fragments on the
      HepG2 cells was investigated by observing the cell proliferation. RESULTS: Two
      different positive clones were obtained and the functional variable sequences
      were identified. Their DNA sequences of the scFv antibody fragments were
      submitted to GenBank (accession nos: AY686498 and AY686499). The soluble scFv
      antibody fragments were successfully expressed in E.coli HB2151. The relative
      molecular mass of the expression products was about 36 ku, according to its
      predicted M(r) value. The two soluble scFv antibody fragments also had specific
      binding activity and obvious growth inhibition properties to HepG2 cells.
      CONCLUSION: The phage library biopanning permits identification of specific
      antibody fragments for hepatocellular carcinoma and affords experiment evidence
      for its immunotherapy study.

PMID- 15996021
TI  - Hydrogen sulfide protects colon cancer cells from chemopreventative agent beta
      phenylethyl isothiocyanate induced apoptosis.
AB  - AIM: Hydrogen sulfide (H(2)S) is a prominent gaseous constituent of the
      gastrointestinal (GI) tract with known cytotoxic properties. Endogenous
      concentrations of H(2)S are reported to range between 0.2-3.4 mmol/L in the GI
      tract of mice and humans. Considering such high levels we speculate that, at non
      toxic concentrations, H(2)S may interact with chemical agents and alter the
      response of colonic epithelium cells to such compounds. The GI tract is a major
      site for the absorption of phytochemical constituents such as isothiocyanates,
      flavonoids, and carotenoids, with each group having a role in the prevention of
      human diseases such as colon cancer. The chemopreventative properties of the
      phytochemical agent beta-phenyethyl isothiocyanate (PEITC) are well recognized.
      However, little is currently known about the physiological or biochemical factors
      present in the GI tract that may influence the biological properties of ITCs. The
      current study was undertaken to determine the effects of H(2)S on PEITC mediated
      apoptosis in colon cancer cells. METHODS: Induction of apoptosis by PEITC in
      human colon cancer HCT116 cells was assessed using classic apoptotic markers
      namely SubG1 population analysis, caspase-3 like activity and nuclear
      fragmentation and condensation coupled with the MTT (3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrasodium bromide) viability assay and LDH leakage. RESULTS: PEITC
      significantly induced apoptosis in HCT116 cells as assessed by SubG1 population
      formation, nuclear condensation, LDH leakage and caspase-3 activity after 24 h,
      these data being significant from control groups (P<0.01). In contrast, co
      treatment of cells with physiological concentrations of H2S (0.1-1 mmol/L)
      prevented PEITC mediated apoptosis as assessed using the parameters described.
      CONCLUSION: PEITC effectively induced cell death in the human adenocarcinoma cell
      line HCT116 in vitro through classic apoptotic mechanisms. However, in the
      presence of H(2)S, apoptosis was abolished. These data suggest that H(2)S may
      play a significant role in the response of colonic epithelial cells to beneficial
      as well as toxic agents present within the GI tract.

PMID- 15996022
TI  - Microsatellite instable double primary cancers of the colorectum and stomach
      exhibit less favorable outcome.
AB  - AIM: To ascertain the adequacy of the microsatellite instability (MSI) as a
      prognostic indicator by assessing MSI status of patients with double primary
      gastric and colorectal cancer (DPGCC). METHODS: Sixteen patients were studied,
      all of whom exhibited sporadic DPGCC, and had no family history of hereditary non
      polyposis colorectal cancer, according to the Amsterdam criteria. A total of 32
      cancers from 16 DPGCC patients, and 216 single primary CRC, were assessed for MSI
      in 5 microsatellite loci, BAT25, BAT26, D2S123, D5S346, and D17S250. RESULTS: MSI
      was observed in 6 (37.5%) of 16 GC and 4 (25.0%) of 16 CRC. Thirty tumors (13.9%)
      out of 216 single primary CRC and one tumor (16.7%) out of 6 double primary CRC
      were found to be microsatellite unstable. Of the 6 GC with MSI in DPGCC, 5
      (31.3%) were MSI-high and one (6.3%) was MSI-low. In 5 of 16 DPGCC patients, the
      cancer recurred in or adjacent to the anastomosis or metastasized to the kidney
      or lung. The MSI-high DPGCC cases were associated with a younger age of onset
      (47.5 years vs 62.5 years), higher frequency of lymph node metastasis (100% vs
      25%), and advanced Dukes stage (C, 100% vs 41.7%), as well as a higher frequency
      of recurrence or metastasis (100% vs 8.3%). Only recurrence or metastasis showed
      statistical significance by Fisher's exact test. CONCLUSION: Our data suggest
      that MSI may play an important role in the development of DPGCC, and that it may
      be used clinically as a molecular predictive marker for recurrence or late
      metastasis of DPGCC.

PMID- 15996023
TI  - Radiosensitivity of human colon cancer cell enhanced by immunoliposomal
      docetaxel.
AB  - AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel.
      METHODS: Immunoliposomal docetaxel was prepared by coupling monoclonal antibody
      against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of
      liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal
      docetaxel or/and irradiation. MTT colorimetric assay was used to estimate
      cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle
      redistribution and apoptosis were determined with flow cytometry. Survivin
      expression in LoVo cells was verified by immunohistochemistry. D801 morphologic
      analysis system was used to semi-quantify immunohistochemical staining of
      survivin. RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in
      a dose-dependent manner. Immunoli-posomal docetaxel yielded a cytotoxicity effect
      at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving
      fraction of LoVo cells showed a dose-dependent response, but there were no
      significant changes as radiation delivered from 4 to 8 Gy. Compared with
      liposomal docetaxel or single dose irradiation, strongly radiopotentiating
      effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of
      immunoliposomal docetaxel could yield sufficient radiosensitivity.
      Immunoliposomal docetaxel were achieved both specificity of the conjugated
      antibody and drug radiosensitization. Combined with radiation, immunoliposomal
      docetaxel significantly increased the percentage of G(2)/M cells and induced
      apoptosis, but significantly decreased the percentage of cells in G(2)/G(1) and S
      phase by comparison with liposomal docetaxel. Immunohistochemical analysis showed
      that the brown stained survivin was mainly in cytoplasm of LoVo cells. Semi
      quantitative analysis of the survivin immunostaining showed that the expression
      of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was
      significantly decreased. CONCLUSION: Immunoliposomal docetaxel is strongly
      effective for target radiosensitation in LoVo colon carcinoma cells, and may
      offer the potential to improve local radiotherapy.

PMID- 15996024
TI  - Effect of caffeic acid phenethyl ester on proliferation and apoptosis of
      colorectal cancer cells in vitro.
AB  - AIM: To study the effect of caffeic acid phenethyl ester (CAPE) on proliferation,
      cell cycle, apoptosis and expression of beta-catenin in cultured human colorectal
      cancer (CRC) cell line HCT116. METHODS: HCT116 cells were treated with CAPE at
      serial concentrations of 80, 40, 20, 10, 5, 2.5 mg/L. The proliferative status of
      HCT116 cells was measured by using methabenzthiazuron (MTT) assay. Cell cycle was
      analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling
      method. The rate of apoptosis was detected by using FCM with annexin V-FITC and
      PI double labeling method. beta-catenin levels were determined by Western
      blotting. beta-catenin localization in HCT116 was determined by indirect
      immunofluorescence. RESULTS: After HCT116 cells were exposed to CAPE (80, 40, 20,
      10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth
      inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM
      analysis showed that the ratio of G(0)/G(1) phase cells increased, S phase ratio
      decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE
      (10, 5, and 2.5 mg/L) for 24 h. CAPE treatment was associated with decreased
      cytoplasmic beta-catenin, nuclear beta-catenin and a concurrent increase in beta
      catenin protein expression at cell-cell junctions. CONCLUSION: CAPE could inhibit
      HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased
      beta-catenin protein expression may mediate the anti-proliferative effects of
      CAPE.

PMID- 15996025
TI  - Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic
      hepatitis C: a randomized controlled trial.
AB  - AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when
      used in combination with interferon. However, RBV-induced anemia is a major
      problem in this therapy. It would be of great clinical importance to ameliorate
      the anemia without reducing the RBV dose. We report here that, Ninjinyoeito
      (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three
      patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV
      with (NYT group) or without (control group) NYT by a randomized selection.
      Eighteen patients completed the treatment schedule, and hemato-biochemical and
      virological effects were evaluated. RESULTS: There was no significant difference
      in biochemical and virological responses between the two groups. However, anemia
      was significantly reduced in the NYT group compared with the control group. The
      maximal decrease of Hb in the NYT group (2.59+/-1.10 g/dL) was significantly (P =
      0.026) smaller than that in the control group (3.71+/-0.97 g/dL). There was no
      significant difference in serum glutathione peroxidase activity, serum RBV
      concentration, and Th1/Th2 balance between the two groups. There was no specific
      adverse effect in NYT administration. CONCLUSION: These results suggest that NYT
      could be used as a supportive remedy to reduce the RBV-induced anemia in the
      treatment of chronic hepatitis C.

PMID- 15996026
TI  - Screening for PreS specific binding ligands with a phage displayed peptides
      library.
AB  - AIM: To construct a random peptide phage display library and search for peptides
      that specifically bind to the PreS region of hepatitis B virus (HBV). METHODS: A
      phage display vector, pFuse8, based on the gene 8 product (pVIII) of M13 phage
      was made and used to construct a random peptide library. E.coli derived
      thioredoxin-PreS was purified with Thio-bond beads, and exploited as the bait
      protein for library screening. Five rounds of bio-panning were performed. The
      PreS-binding specificities of enriched phages were characterized with phage ELISA
      assay. RESULTS: A phage display vector was successfully constructed as
      demonstrated to present a pVIII fused HBV PreS1 epitope on the phage surface with
      a high efficiency. A cysteine confined random peptide library was constructed
      containing independent clones exceeding 5+/-10(8) clone forming unit (CFU). A
      pool of phages showing a PreS-binding specificity was obtained after the
      screening against thio-PreS with an enrichment of approximately 400 times. Five
      phages with high PreS-binding specificities were selected and characterized.
      Sequences of the peptides displayed on these phages were determined. CONCLUSION:
      A phage library has been constructed, with random peptides displaying as pVIII
      fusion proteins. Specific PreS-binding peptides have been obtained, which may be
      useful for developing antivirals against HBV infection.

PMID- 15996027
TI  - Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's
      disease and contributes to accelerated epithelial wound healing in vitro.
AB  - AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like
      ligands, the ephrins, represent a bi-directional cell-cell contact signaling
      system that directs epithelial movements in development. The meaning of this
      system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA
      expression in the intestinal epithelium of healthy controls and patients with
      inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all
      Eph/ephrin family members in normal small intestine and colon were established by
      real-time RT-PCR. In addition, differential expression in IBD was investigated by
      cDNA array technology, and validated by both real-time RT-PCR and
      immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were
      analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult
      intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside
      the known prominent co-expression of EphA2 and ephrinA1, we found abundantly co
      expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by
      real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both
      perilesional and lesional intestinal epithelial cells of IBD patients, suggesting
      a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin
      B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a
      significant dose-dependent acceleration of wound closure. Furthermore,
      fluorescence microscopy showed that EphB1-Fc induced coordinated migration of
      wound edge cells is associated with enhanced formation of lamellipodial
      protrusions into the wound, increased actin stress fiber assembly and production
      of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent
      a novel protective mechanism that promotes intestinal epithelial wound healing,
      with potential impact on epithelial restitution in IBD.

PMID- 15996028
TI  - Effect of the ulcerogenic agents ethanol, acetylsalicylic acid and taurocholate
      on actin cytoskeleton and cell motility in cultured rat gastric mucosal cells.
AB  - AIM: To assess the effects of ulcerogenic agents on actin cytoskeleton and cell
      motility and the contribution of oxidative stress. METHODS: Rat gastric mucosal
      cell monolayers were cultured on coverslips. The cells were exposed, with or
      without allopurinol (2 mmol/L), for 15 min to ethanol (10-150 mL/L), ASA (1-20
      mmol/L) or taurocholate (1-20 mmol/L), then the cells were processed for actin
      and vinculin staining. Cell migration after wounding was also measured. RESULTS:
      Exposure to 10 mL/L ethanol caused divergence of zonula adherens-associated actin
      bundles of adjacent cells and decreased rate of migration. These actions were
      opposed by xanthine oxidase inhibitor allopurinol. Exposure to 50 mL/L ethanol
      induced degradation and divergence of zonula adherens-associated vinculin from
      adjacent cells, which was, again, partially reverted by allopurinol. With 1
      mmol/L ASA actin filaments became shorter and thicker. However, higher
      concentrations (10, 20 mmol/L) of ASA returned microfilaments thinner and longer,
      and decreased rate of migration. Zonula adherens-associated actin bundles were
      moderately distorted with 10 mmol/L ASA and with 10 mmol/L taurocholate. Exposure
      to taurocholate provoked changes resembling those of ASA. Taurocholate 5-20
      mmol/L decreased the rate of migration dose dependently. The effects of ASA and
      taurocholate were not prevented by allopurinol. CONCLUSION: All ulcerogenic
      agents decreased the rate of migration dose dependently and induced divergence of
      zonula adherens-associated actin bundles of adjacent cells. In addition, ethanol
      and ASA caused degradation of actin cytoskeleton. Oxidative stress seems to
      underlie ethanol, but not ASA or taurocholate, induced cytoskeletal damage.

PMID- 15996029
TI  - Acupuncture for irritable bowel syndrome: a blinded placebo-controlled trial.
AB  - AIM: Irritable bowel syndrome (IBS) is a common disorder and many patients fail
      to find adequate relief from conventional therapies for their symptoms. This
      study tests the claim that acupuncture is effective for a majority of these
      patients. METHODS: A prospective, blinded, sham acupuncture-controlled trial of
      traditional Chinese acupuncture was performed at a single postgraduate teaching
      hospital in Europe. Sixty patients with well-established IBS were recruited. The
      blinded comparator was sham acupuncture administered by the second of two
      acupuncturists who alone was aware of the randomization, and who otherwise
      followed the prescription of the first. The primary end-point was a defined fall
      in the symptom score at 13 wk (by intention to treat). The prior expectation was
      a 30% placebo response, and a response rate of 70% from acupuncture, for which
      the study was adequately powered. RESULTS: Patients in treated and sham groups
      improved significantly during the study-mean improvement in scores being equal
      (minus 1.9) and significant for both (P<0.05; one-tailed t test). There was a
      small numeric but non-significant difference between the response rate in
      patients receiving acupuncture (40.7%) and sham treatment (31.2%). Several
      secondary end-points marginally favored active treatment, but an improved symptom
      score of any degree of magnitude occurred more often with sham therapy (65.6% vs
      59.2%). For no criterion was statistical significance approached. CONCLUSION:
      Traditional Chinese acupuncture is relatively ineffective in IBS in the European
      hospital setting, and the magnitude of any effect appears insufficient to warrant
      investment in acupuncture services.

PMID- 15996030
TI  - Adeno-associated virus mediated interferon-gamma inhibits the progression of
      hepatic fibrosis in vitro and in vivo.
AB  - AIM: To investigate the effects of adeno-associated virus (AAV) mediated
      expression of human interferon-gamma for gene therapy in experimental hepatic
      fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV
      encoding human INF-gamma (rAAV- INF-gamma) and took the primary rat hepatic
      stellate cells and carbon tetrachloride induced rats as the experimental hepatic
      fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to
      reveal the expression of alpha-SMA, the marker protein expressed in hepatic
      stellate cells. The mRNA expression of TGF-beta, TIMP-1, and MMP-13 were analyzed
      by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum
      AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated
      efficient expression of human INF-gamma, which inhibit the activation of hepatic
      stellate cells, decrease the expression of alpha-SMA and mRNA of TIMP-1, TGF
      beta, with the MMP-13 unchanged. In vivo study, the histological examination
      revealed that rAAV- INF-gamma could inhibit the progression of the hepatic
      fibrosis. In the rAAV-INF-gamma induced group, the hydroxyproline content and
      serum AST, ALT level were decreased to 177+/-28 microg/g wet liver, 668.5+/
      140.0, 458.4+/-123.5 U/L, compare with the fibrosis control group 236+/-31
      microg/g wet liver, 1 019.1+/-276.3, 770.5+/-154.3 U/L, respectively (P<0.01).
      mRNA expression of TIMP-1 in the rAAV-INF-gamma induced rat liver was decreased
      while no significant change was observed in TGF-beta and MMP-13. CONCLUSION: All
      these results indicated that rAAV-INF-gamma has potential effects for gene
      therapy of hepatic fibrosis, which could inhibit the progression of hepatic
      fibrosis.

PMID- 15996031
TI  - Lansoprazole prevents experimental gastric injury induced by non-steroidal anti
      inflammatory drugs through a reduction of mucosal oxidative damage.
AB  - AIM: This study investigated the mechanisms of protection afforded by the proton
      pump inhibitor lansoprazole against gastric injury induced by different non
      steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley
      rats were orally treated with indomethacin (100 micromol/kg), diclofenac (60
      micromol/kg), piroxicam (150 micromol/kg) or ketoprofen (150 micromol/kg). Thirty
      minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90
      micromol/kg. Four hours after the end of treatments, the following parameters
      were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO)
      or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription
      polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion
      in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 micromol/L)
      on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate.
      RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with
      neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA
      contents, as well as a decrease in GSH levels were detected in the gastric mucosa
      of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal
      cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral
      dose of 18 micromol/kg lansoprazole partly counteracted diclofenac-induced
      mucosal damage, whereas at 90 micromol/kg it markedly prevented injuries evoked
      by all test NSAIDs. Lansoprazole at 90 micromol/kg reversed also the effects of
      NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the
      decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression.
      However, both lansoprazole doses markedly inhibited acid secretion in pylorus
      ligated rats. Lansoprazole concentration-dependently reduced the oxidation of
      LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of
      acid secretion, lansoprazole protection against NSAID-induced gastric damage
      depends on a reduction in mucosal oxidative injury, which is also responsible for
      an increment of sulfhydryl radical bioavailability. It is also suggested that
      lansoprazole does not influence the down-regulation of gastric prostaglandin
      production associated with NSAID treatment.

PMID- 15996032
TI  - Ultrasonography of splenic abnormalities.
AB  - AIM: This report gives a comprehensive overview of ultrasonography of splenic
      abnormalities. Certain ultrasonic features are also discussed with pathologic
      correlation. METHODS: We review the typical ultrasonic characteristics of a wide
      range of splenic lesions, illustrating them with images obtained in our
      institution from 2000 to 2003. One hundred and three patients (47 men, 56 women),
      with a mean age of 54 years (range 9-92 years), were found to have an abnormal
      ultrasonic pattern of spleen. RESULTS: We describe the ultrasonic features of
      various splenic lesions such as accessory spleen, splenomegaly, cysts, cavernous
      hemangiomas, lymphomas, abscesses, metastatic tumors, splenic infarctions,
      hematomas, and rupture, based on traditional gray-scale and color Doppler
      sonography. CONCLUSION: Ultrasound is a widely available, noninvasive, and useful
      means of diagnosing splenic abnormalities. A combination of ultrasonic
      characteristics and clinical data may provide an accurate diagnosis. If the US
      appearance alone is not enough, US may also be used to guide biopsy of suspicious
      lesions.

PMID- 15996034
TI  - Development of a semi-quantitative food frequency questionnaire for middle-aged
      inhabitants in the Chaoshan area, China.
AB  - AIM: This paper aims to develop a data-based semi-quantitative food frequency
      questionnaire (SQFFQ) covering both urban and rural areas in the Chaoshan region
      of Guangdong Province, China, for the investigation of relationships between food
      intake and lifestyle-related diseases among middle-aged Chinese. METHODS: We
      recruited 417 subjects from the general population and performed an assessment of
      the diet, using a 3-d weighed dietary record survey. We employed contribution
      analysis (CA) and multiple regression analysis (MRA) to select food items
      covering up to a 90% contribution and a 0.90 R(2), respectively. The total number
      of food items consumed was 523 (443 in the urban and 417 in the rural population)
      and the intake of 29 nutrients was calculated according to the actual consumption
      by foods/recipes. RESULTS: The CA selected 233, 194, and 183 foods/recipes for
      the combined, the urban and the rural areas, respectively, and then 196, 157, and
      160 were chosen by the MRA. Finally, 125 foods/recipes were selected for the
      final questionnaire. The frequencies were classified into eight categories and
      standard portion sizes were also calculated. CONCLUSION: For adoption of the area
      specific SQFFQ, validity and reproducibility tests are now planned to determine
      how the combined SQFFQ performs in actual assessment of disease risk and benefit.

PMID- 15996033
TI  - Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in
      the treatment of erosive esophagitis: a meta-analysis.
AB  - AIM: To systematically evaluate the efficacy of H(2)-receptor antagonists
      (H(2)RAs) and proton pump inhibitors in healing erosive esophagitis (EE).
      METHODS: A meta-analysis was performed. A literature search was conducted in
      PubMed, Medline, Embase, and Cochrane databases to include randomized controlled
      head-to-head comparative trials evaluating the efficacy of H(2)RAs or proton pump
      inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI)
      were calculated under a random-effects model. RESULTS: RRs of cumulative healing
      rates for each comparison at 8 wk were: high dose vs standard dose H(2)RAs, 1.17
      (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose
      H(2)RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs
      standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors
      produced consistently greater healing rates than H(2)RAs of all doses across all
      grades of esophagitis, including patients refractory to H(2)RAs. Healing rates
      achieved with standard dose omeprazole were similar to those with other proton
      pump inhibitors in all grades of esophagitis. CONCLUSION: H(2)RAs are less
      effective for treating patients with erosive esophagitis, especially in those
      with severe forms of esophagitis. Standard dose proton pump inhibitors are
      significantly more effective than H(2)RAs in healing esophagitis of all grades.
      Proton pump inhibitors given at the recommended dose are equally effective for
      healing esophagitis.

PMID- 15996035
TI  - Prevalence of hepatitis C virus infection and its related risk factors in drug
      abuser prisoners in Hamedan--Iran.
AB  - AIM: Recent studies in Iran has shown that prevalence of hepatitis C virus (HCV)
      infection among Iranian prisoners is high, in spite of low HCV seroprevalence in
      general population. METHODS: This study was carried out in the central prison of
      Hamedan--Iran, in year 2002. Inmates were interviewed using a standard
      questionnaire including demographic, imprisonment history and HCV-related risk
      behaviors items. Thereafter, the sera drawn from the participants were tested for
      anti-HIV and anti-HCV antibodies. RESULTS: A total number of 427 drug abuser
      inmates participated in our study. Three hundred and ninety-seven (93%) were men
      and 30 (7%) were women. Total number of IV drug abusers (IDA) and non-IV drug
      abusers (NIDA) was 149 (34.9%) and 278 (65.1%), respectively. The overall rate of
      antibody positivity among inmates was 0.9% for HIV and 30% for HCV. Of all IDAs,
      31.5% and of NIDAs, 29.1% had serological evidence of HCV infection. CONCLUSION:
      The seroprevalence of HCV infection among drug abuser prisoners in comparison
      with the general population in Iran, is very high (30% vs in italics 0.2%). Our
      results indicate the importance of policies to prevent transmission of HCV
      infection during and following incarceration.

PMID- 15996036
TI  - Association between TRAIL expression on peripheral blood lymphocytes and liver
      damage in chronic hepatitis B.
AB  - AIM: To explore a novel mechanism for tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL), upregulation of CD4(+) and CD8(+) T lymphocytes
      participating in the patho-physiological process of chronic hepatitis B (CHB).
      METHODS: The levels of serum soluble TRAIL (sTRAIL), serum IFN-gamma and membrane
      bound TRAIL expression on peripheral leucocytes from 58 CHB patients were
      examined by ELISA and flow cytometry respectively. The levels of TRAIL were
      compared with the baseline levels of 17 healthy controls, and correlation
      analysis was performed between ALT, TBIL, PT, morphological change in hepatic
      tissues, and serum IFN-gamma. RESULTS: The results showed that TRAIL levels on
      membranes of CD4(+), CD8(+) T cells in CHB patients were much higher than those
      in healthy controls (P<0.001), and were correlated with serum TBIL (r = 0.354, P
      = 0.008 for CD4(+) and r = 0.522, P = 0.000 for CD8(+), respectively), ALT (r =
      0.393, P = 0.003 for CD8(+)), PT (r = 0.385, P = 0.004 for CD8(+)) and serum IFN
      gamma level (r = 0.302, P = 0.011 for CD4(+) and r = 0.307, P = 0.009 for
      CD8(+)). On the contrary to membrane-bound TRAIL expression, serum level of
      sTRAIL was not correlated with that of TBIL and PT, though it was higher than
      that of the normal population and was positively correlated with serum HBeAg
      expression (r = 0.695, P = 0.001). CONCLUSION: The expression level of TRAIL on
      the membrane of lymphocytes was upregulated and associated with the liver injury
      in CHB patients. These findings suggest that upregulation of TRAIL expression may
      be induced by virus antigen and inflammatory cytokine IFN-gamma.

PMID- 15996037
TI  - Preparation of anti-mouse caspase-12 mRNA hammerhead ribozyme and identification
      of its activity in vitro.
AB  - AIM: To prepare and identify specific anti-mouse caspase-12 hammerhead ribozymes
      in vitro, in order to select a more effective ribozyme against mouse caspase-12
      as a potential tool to rescue cells from endoplasmic reticulum stress induced
      apoptosis. METHODS: Two hammerhead ribozymes directed separately against 138 and
      218 site of nucleotide of mouse caspase-12 mRNA were designed by computer
      software, and their DNA sequences were synthesized. The synthesized ribozymes
      were cloned into an eukaryotic expression vector-neo(r)pBSKU6 and embedded in U6
      SnRNA context for further study. Mouse caspase-12 gene segment was cloned into
      PGEM-T vector under the control of T7 RNA polymerase promoter (containing gene
      sequence from positions nt 41 to nt 894) as target. In vitro transcription both
      the ribozymes and target utilize T7 promoter. The target was labeled with (alpha-
      (32)P)UTP, while ribozymes were not labeled. After gel purification the RNAs were
      dissolved in RNase free water. Ribozyme and target were incubated for 90 min at
      37 degrees in reaction buffer (40 mmol/L Tris-HCL, pH 7.5, 10 mmol/L Mg(2+)).
      Molar ratio of ribozyme vs target was 30:1. Samples were analyzed on 6%
      PAGE(containing 8 mol/L urea). RESULTS: Both caspase-12 and ribozyme gene
      sequences were successfully cloned into expression vector confirmed by
      sequencing. Ribozymes and caspase-12 mRNA were obtained by in vitro
      transcription. Cleavage experiment showed that in a physiological similar
      condition (37 degrees, pH 7.5), Rz138 and Rz218 both cleaved targets at predicted
      sites, for Rz138 the cleavage efficiency was about 100%, for Rz218 the value was
      36.66%. CONCLUSION: Rz138 prepared in vitro can site specific cleave mouse
      caspase-12 mRNA with an excellent efficiency. It shows a potential to suppress
      the expression of caspase-12 in vivo, thus provided a new way to protect cells
      from ER stress induced apoptosis.

PMID- 15996038
TI  - Comparative study on radiosensitivity of various tumor cells and human normal
      liver cells.
AB  - AIM: To investigate the radiation response of various human tumor cells and
      normal liver cells. METHODS: Cell lines of human hepatoma cells (SMMC-7721),
      liver cells (L02), melanoma cells (A375) and cervical tumor (HeLa) were
      irradiated with (60)Co gamma-rays. Cell survive was documented by a colony assay.
      Chromatid breaks were measured by counting the number of chromatid breaks and
      isochromatid breaks immediately after prematurely chromosome condensed by
      Calyculin-A. RESULTS: Linear quadratic survival curve was observed in all of four
      cell lines, and dose-dependent increase in radiation-induced chromatid and
      isochromatid breaks were observed in GB2B phase. Among these four cell lines,
      A375 was most sensitive to radiation, while, L02 had the lowest radiosensitivity.
      For normal liver cells, chromatid breaks were easy to be repaired, isochromatid
      breaks were difficult to be repaired. CONCLUSION: The results suggest that the
      gamma-rays induced chromatid breaks can be possibly used as a good predictor of
      radiosensitivity, also, unrejoined isochromatid breaks probably tightly related
      with cell cancerization.

PMID- 15996040
TI  - Correlation of Chlamydia pneumoniae infection with primary biliary cirrhosis.
AB  - AIM: To evaluate the association between Chlamydia pneumoniae (Cpn) infection and
      primary biliary cirrhosis (PBC). METHODS: Cpn IgG and IgM were determined by
      enzyme-linked immunosorbent assay (ELISA) in 41 well-established PBC patients and
      two race-matched control groups (post-hepatitis cirrhosis, n = 70; healthy
      controls, n = 57). RESULTS: The mean level and seroprevalence of Cpn IgG in PBC
      group and post-hepatitis cirrhosis (PHC) group were significantly higher than
      those in healthy controls (46.8+/-43.4 RU/mL, 49.5+/-45.2 RU/mL vs 28.3+/-32.7
      RU/mL; 68.3%, 71.4%, 42.1%, respectively; P<0.05). There was a remarkably
      elevated seroprevalence of Cpn IgM in patients with PBC (22.0%) compared to the
      PHC and healthy control (HC) groups. For the PBC patients versus the HCs, the
      odds ratios (ORs) of the presence of Cpn IgG and IgM were 2.7 (95% CI 0.9-6.1)
      and 5.1 (95% CI 1.4-18.5), respectively. Though there was no correlation in the
      level of Cpn IgG with total IgG in sera of patients with PBC (r = -0.857, P =
      0.344>0.05), Cpn IgM was related with the abnormally high concentrations of total
      IgM in PBC group. CONCLUSION: The results of this study do not support the
      hypothesis that infection with Chlamydia pneumoniae may be a triggering agent or
      even a causative agent in PBC, but suggest that Chlamydia pneumoniae infection
      probably contributes to the high level of IgM present in most patients with PBC.

PMID- 15996039
TI  - Genetic alterations of hepatocellular carcinoma by random amplified polymorphic
      DNA analysis and cloning sequencing of tumor differential DNA fragment.
AB  - AIM: To study the genetic alterations and their association with
      clinicopathological characteristics of hepatocellular carcinoma (HCC), and to
      find the tumor related DNA fragments. METHODS: DNA isolated from tumors and
      corresponding noncancerous liver tissues of 56 HCC patients was amplified by
      random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers.
      The RAPD bands showing obvious differences in tumor tissue DNA corresponding to
      that of normal tissue were separated, purified, cloned and sequenced. DNA
      sequences were analyzed and compared with GenBank data. RESULTS: A total of 56
      cases of HCC were demonstrated to have genetic alterations, which were detected
      by at least one primer. The detestability of genetic alterations ranged from 20%
      to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor
      size, histological grade, tumor capsule, as well as tumor intrahepatic
      metastasis, might be correlated with genetic alterations on certain primers. A
      band with a higher intensity of 480 bp or so amplified fragments in tumor DNA
      relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4.
      Sequence analysis of these fragments showed 91% homology with Homo sapiens double
      homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event
      in HCC, and tumor related DNA fragments have been found in this study, which may
      be associated with hepatocarcinogenesis. RAPD is an effective method for the
      identification and analysis of genetic alterations in HCC, and may provide new
      information for further evaluating the molecular mechanism of
      hepatocarcinogenesis.

PMID- 15996041
TI  - Splenic hemangiopericytoma and serosal cavernous hemangiomatosis of the adjacent
      colon.
AB  - A healthy 31-years-old man presented with a three-year history of abdominal
      discomfort. Radiological examinations revealed multifocal tumoral lesions in the
      spleen. The patient underwent splenectomy for differential diagnosis and
      treatment. During the operation, in addition to the splenic masses, there were
      also multiple millimetric purpuric-like lesions on the colonic serosal surfaces
      adjacent to the splenic hilus. One of them was excised. Histologic examination
      showed hemangiopericytoma of the spleen and cavernous hemangioma of the adjacent
      colon. This is the first report showing the close association of these two
      distinct lesions with vascular origin in the literature. Despite not having any
      apparent evidence, there may be a sequential relationship between the
      hemangiopericytoma of the spleen and cavernous hemangiomas.

PMID- 15996042
TI  - Acute exacerbation of autoimmune hepatitis induced by Twinrix.
AB  - We report on a 26-year-old man who presented with severe jaundice and elevated
      serum liver enzyme activities after having received a dose of Twinrix. In his
      past medical history, jaundice or abnormal liver function tests were never
      recorded. Following admission, an elevated immunoglobulin G level and antinuclear
      antibodies at a titer of 320 with a homogenous pattern were found. Histology of a
      liver biopsy showed marked bridging liver fibrosis and a chronic inflammation,
      compatible with autoimmune hepatitis. Treatment was started with budesonide and
      ursodeoxycholic acid, and led to complete normalization of the pathological liver
      function tests. We believe that Twinrix led to an acute exacerbation of an
      unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be
      clarified. It is tempting to speculate that inactivated hepatitis A virus and/or
      recombinant surface antigen of the hepatitis B virus -as seen in patients with
      chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with
      interferon alpha-might have been responsible for disease exacerbation.

PMID- 15996043
TI  - Solid-pseudopapillary tumor of the pancreatic tail.
AB  - We report a case of the rare solid-pseudopapillary tumor of the pancreas. In
      contrast to other pancreatic tumors, the solid-pseudopapillary tumor has a
      favorable prognosis. The 60-year-old female patient we report on here was treated
      by left pancreatic resection combined with splenectomy for a non-metastasizing
      tumor of the pancreas. A solid-pseudopapillary tumor was found on histology. The
      patient had no signs of metastases at present. Since a microscopically invasive
      tumor growth is assumed, oncologically curative resection should be preferred vs
      the less radical enucleation. The rare solid-pseudopapillary tumor of the
      pancreas has a good prognosis after successful oncological resection.

PMID- 15996044
TI  - Diagnostic laparoscopy and laparoscopic ultrasonography with local anesthesia in
      hepatocellular carcinoma.
AB  - Diagnosis of hepatocellular carcinoma (HCC), a common digestive malignancy,
      remains a challenge. The aim of this study was to evaluate the feasibility of
      performing laparoscopy and laparoscopic ultrasound with local anesthesia as a
      diagnostic procedure in HCC. Laparoscopy and laparoscopic ultrasound with local
      anesthesia was performed in the gastrointestinal endoscopy unit in three patients
      diagnosed of HCC. Endoscopy staged diffuse liver disease. Laparoscopic
      ultrasonography identified all liver tumors not visible during endoscopy and
      guided needle biopsy in one case. No complications happened. In conclusion,
      laparoscopy and laparoscopic ultrasound, performed as a minimally invasive
      diagnostic procedure can be a safe and very promising tool in planning therapy of
      HCC.

PMID- 15996045
TI  - Familial gastric cancers with Li-Fraumeni Syndrome: a case repast.

PMID- 15996046
TI  - New Glucocorticoids on the Horizon: Repress, Don't Activate!
AB  - Glucocorticoids are highly effective drugs; their immunosuppressive and
      antiinflammatory actions are used in the treatment of many rheumatic and other
      inflammatory diseases. However, their use is sometimes considerably limited by
      numerous adverse reactions. For this reason, great efforts have been made in
      recent years to develop innovative glucocorticoids or glucocorticoid receptor
      ligands that have improved therapeutic effect/adverse reaction ratio. We
      summarize the position and critically discuss the following products that are
      currently under development: (1) selective glucocorticoid receptor agonists
      (SEGRA or dissociating glucocorticoids); (2) nitrosteroids; and (3) long
      circulating liposomal glucocorticoids. Finally, we describe the state of research
      on membrane-bound glucocorticoid receptors as possible further targets for
      specific glucocorticoid actions.

PMID- 15996048
TI  - Biologic agents and their use in resource-poor countries.

PMID- 15996049
TI  - Bone loss in ankylosing spondylitis: can we put the puzzle together?

PMID- 15996050
TI  - The diagnosis and management of patients with giant cell arteritis.

PMID- 15996051
TI  - Nonsteroidal antiinflammatory drug gastropathy: we started it, why don't we stop
      it?

PMID- 15996052
TI  - The proteasome and its implications in rheumatology.

PMID- 15996053
TI  - Selective IgA immune unresponsiveness to Proteus mirabilis fumarate reductase A
      chain in rheumatoid arthritis.
AB  - OBJECTIVE: To determine if selective immune unresponsiveness to microbial
      antigens is associated with predisposition to rheumatoid arthritis (RA). METHODS:
      Proteins from Proteus mirabilis lysate were isolated by SDS-PAGE and examined by
      Western blotting for antibody responses in sera from patients with RA compared to
      healthy subjects and patients with psoriatic arthritis (PsA). RESULTS: Although
      RA patients had marked IgA immune responses to many P. mirabilis proteins
      compared to healthy subjects, selective unresponsiveness was found in RA to a 66
      kDa protein identified as fumarate reductase A-chain (FRD-A) by mass
      spectroscopy. This was confirmed in Western blots with recombinant FRD-A from P.
      mirabilis. IgA unresponsiveness to FRD-A was found in 21/59 (35.6%) RA patients
      compared to 7/63 (11.1%) healthy individuals (p < 0.01) and 6/52 (11.5%) patients
      with PsA (p < 0.01). IgA unresponsiveness to FRD-A was present in 20/46 (43.5%)
      RA patients with IgA rheumatoid factors (RF) compared to 1/13 (7.7%) without RF
      (p < 0.025). CONCLUSION: Our results identify a selective hole in the IgA immune
      repertoire for P. mirabilis FRD-A in a subset of IgA RF-positive patients with
      RA.

PMID- 15996054
TI  - Treatment with tumor necrosis factor blockers is associated with a lower
      incidence of first cardiovascular events in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the risk of cardiovascular disease (CVD) in patients
      with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF)
      inhibitors, compared to a standard RA population. METHODS: Patients were
      recruited from a regional register, which includes over 90% of patients with RA
      started on TNF blockers in 1999 or later, and a local community based cohort of
      RA patients, established in 1997. Of a total of 983 patients in the combined
      cohort, 531 received treatment with etanercept or infliximab during the study
      period. The total cohort (n = 983) was linked with national registers for
      inpatient care and cause of death through December 31, 2001. CVD was defined as
      the first inpatient care or death from CVD without inpatient care for CVD prior
      to study entry. First CVD events in those treated versus not treated with TNF
      blockers were estimated, using age and sex adjusted incidence density
      computations with treatment and disease severity markers as time-dependent
      covariates. RESULTS: In the anti-TNF-treated patients, the age-sex adjusted
      incidence rate of first CVD event was 14.0/1000 person-years at risk (95% CI 5.7
      22.4), compared with 35.4/1000 person-years (95% CI 16.5-54.4) in those not
      treated. Controlling for disability, the age-sex adjusted rate ratio was 0.46
      (95% CI 0.25-0.85, p = 0.013) in anti-TNF-treated versus not treated. CONCLUSION:
      These findings suggest that the risk of developing CVD is lower in patients with
      RA treated with TNF blockers. This is compatible with the hypothesis that
      inflammation contributes to the development of cardiovascular events.

PMID- 15996055
TI  - High-grade C-reactive protein elevation correlates with accelerated atherogenesis
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) are at greater risk of
      developing cardiovascular events compared with individuals without RA. Increased
      risk for cardiovascular disease in these patients is a consequence of
      atherosclerosis. Case-control studies have shown that increased intima-media
      thickness (IMT) of the common carotid artery is an indicator of generalized
      atherosclerosis. Some investigators have suggested that the development of
      atherosclerosis in RA may be related to the magnitude and chronicity of the
      systemic inflammation. We examined the relationship between carotid IMT to C
      reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are the
      most commonly assessed markers of inflammatory response in patients with RA.
      METHODS: Retrospective review of CRP and ESR values in 47 patients with longterm
      actively treated (at least 5 years) RA without clinically evident atherosclerosis
      or its complications, who had been studied for carotid IMT with high resolution B
      mode ultrasound. RESULTS: No correlation between ESR and carotid IMT was
      observed. However, a correlation was found between the maximum CRP values and the
      carotid IMT (p = 0.009). The distribution of patients in 4 quartiles according to
      the average CRP values showed significant differences in the carotid IMT (p =
      0.03). Those exhibiting the highest mean CRP values (quartile 4) had greater
      carotid IMT. There was no correlation between CRP at the time of disease
      diagnosis or at the time of the ultrasound study and the carotid IMT. CONCLUSION:
      Our study confirms that the magnitude and chronicity of the inflammatory response
      measured by CRP correlates directly with the presence of atherosclerosis in
      patients with RA.

PMID- 15996056
TI  - Importance of C-reactive protein in regulating monocyte tissue factor expression
      in patients with inflammatory rheumatic diseases.
AB  - OBJECTIVE: To determine the relationship between plasma C-reactive protein (CRP)
      concentrations and monocyte tissue factor (TF) expression induced in vitro by
      combinations of CRP, ss2-glycoprotein I (ss2-GPI), and lipopolysaccharide (LPS).
      METHODS: Peripheral blood mononuclear cells (PBMC) from 26 healthy individuals
      and 31 patients with inflammatory rheumatic diseases (IRD) were cultured with
      combinations of CRP, purified or recombinant ss2-GPI, and LPS and monocyte TF
      procoagulant activity, TF antigen, and TF mRNA were measured. Results were
      examined against plasma CRP levels. RESULTS: Monocytes from patients with IRD
      expressed significantly more TF when stimulated with CRP compared to normal
      monocytes (p = 0.002). An incremental positive correlation was observed between
      plasma CRP levels and TF induced by CRP or ss2-GPI. Significantly more TF was
      induced with CRP combined with ss2-GPI, compared to ss2-GPI alone, either with
      costimulation or CRP priming. Conversely, when combined with LPS, ss2-GPI
      suppressed TF induction in a dose-dependent manner on normal PBMC but not on PBMC
      from patients with IRD. The loss of suppression correlated strongly with plasma
      CRP levels. CONCLUSION: This study shows a remarkably consistent effect of CRP on
      monocyte TF expression. Systemic inflammation associated with elevated plasma CRP
      conferred a phenotype on PBMC, whereby incremental priming with respect to TF
      expression (induced by CRP itself or ss2-GPI) was apparent, and ss2-GPI-mediated
      inhibition of TF expression induced by LPS was incrementally lost. CRP regulation
      of monocyte TF could contribute to the higher than expected atherosclerotic
      vascular disease seen in patients with IRD.

PMID- 15996057
TI  - Longterm safety, efficacy, and radiographic outcome with etanercept treatment in
      patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate safety, efficacy, and radiographic progression in patients
      with early rheumatoid arthritis (RA) undergoing longterm treatment with
      etanercept. METHODS: Patients with early RA (disease duration of 3 years or less)
      who had completed a 2-year efficacy study comparing etanercept and methotrexate
      (MTX) were followed in an extension where they received 25 mg etanercept twice
      weekly. Safety was summarized descriptively and compared with data from the
      efficacy study. Efficacy and radiographic progression were assessed using
      American College of Rheumatology response criteria, disease activity scores, and
      Total Sharp Score (TSS). RESULTS: Rates of serious adverse events and serious
      infections did not increase with longterm exposure to etanercept, and were
      similar to rates reported for the blinded portion of the efficacy study. Efficacy
      was sustained in patients who completed 5 years of etanercept treatment at the
      time of this report (N = 201), even in those who decreased or discontinued use of
      MTX or corticosteroids. No radiographic progression (change in TSS < or = 0) was
      seen in 55% of patients with 5-year radiographs; negative change (TSS < 0) was
      seen in 11%. CONCLUSION: Etanercept treatment in patients with early RA was
      generally well tolerated for up to 5 years. The results indicate sustained
      efficacy and decreased rate of radiographic progression. The rate of radiographic
      progression was low compared with other studies, emphasizing the benefit gained
      in patients with early aggressive RA who undergo longterm treatment with
      etanercept.

PMID- 15996058
TI  - Does age bias the aggressive treatment of elderly patients with rheumatoid
      arthritis?
AB  - OBJECTIVE: Age bias has been reported to result in undertreatment of elderly
      patients with various medical conditions. We investigated whether a similar bias
      exists in the treatment of elderly patients with rheumatoid arthritis (ELDRA)
      compared to matched younger controls (YRA). METHODS: We performed an analysis of
      our RA clinical research registry to determine whether any differences exist
      between ELDRA and YRA patients with respect to use of combination disease
      modifying antirheumatic drugs (DMARD), biologic agents, corticosteroids, and
      nonsteroidal antiinflammatory drugs (NSAID). We also determined whether any
      difference in clinical status could be identified. RESULTS: Forty-nine female
      ELDRA subjects (age > 70 yrs) with insurance were matched for sex, insurance
      status, and duration of disease to YRA subjects (< 60 yrs). No statistically
      significant difference was noted in number of DMARD currently in use (1.24 +/-
      0.78 vs 1.24 +/- 0.69, p = 1.00), or number of patients using biologic agents (25
      vs 30; p = 0.31), corticosteroids (16 vs 11; p = 0.26), or NSAID (26 vs 36; p =
      0.06). ELDRA and YRA patients also reported similar pain (judged using a visual
      analog scale, VAS; 3.5 +/- 2.6 cm vs 3.4 +/- 2.2 cm), fatigue (VAS 3.2 +/- 2.7 cm
      vs 3.9 +/- 2.9 cm), global assessment (VAS 2.8 +/- 2.2 cm vs 3.5 +/- 2.6 cm), and
      Health Assessment Questionnaire disability scores (0.82 +/- 0.5 vs 0.73 +/- 0.5).
      CONCLUSION: In this cohort of elderly patients with RA, we detected no bias in
      the use of RA treatment compared with younger controls. Clinical RA measures also
      showed that these elderly patients with RA were faring at least as well as the
      younger controls; they were not relatively undertreated.

PMID- 15996059
TI  - Diet and risk of rheumatoid arthritis in a prospective cohort.
AB  - OBJECTIVE: To assess the association between dietary factors and risk of
      rheumatoid arthritis (RA) in a large prospective cohort. METHODS: Information
      about dietary intake was obtained from a detailed self-administered food
      frequency questionnaire completed by 57,053 individuals who participated in a
      prospective cohort. Linking the cohort to the Danish National Patient Registry we
      identified patients who developed RA. A rheumatologist scrutinized original
      medical records for these individuals in order to confirm the diagnosis of RA.
      Cox proportional hazards regression analyses were performed for dietary and
      lifestyle factors. RESULTS: The average time of followup in the cohort was 5.3
      years (range < 1 mo to 7.7 yrs). Sixty-nine individuals were identified with
      confirmed incident RA. In multivariate models each increase in intake of 30 g fat
      fish (> or = 8 g fat/100 g fish) per day was associated with 49% reduction in the
      risk of RA (p = 0.06), whereas medium fat fish (3-7 g fat/100 g fish) was
      associated with significantly increased risk of RA. Intake of fruit and coffee
      was not associated with risk of RA. Furthermore, no associations were found
      between risk of RA and intake of a range of other dietary factors including long
      chain fatty acids, olive oil, vitamins A, E, C, D, zinc, selenium, iron, and
      meat. CONCLUSION: The limited number of patients who developed RA during followup
      of our large cohort prevented us from concluding that dietary factors are
      unimportant as risk factors for RA. It appears, however, that if dietary factors
      are important modifiers of RA risk, they must play a role more than a few years
      before clinical diagnosis.

PMID- 15996060
TI  - Sex hormone concentrations in patients with rheumatoid arthritis are not
      normalized during 12 weeks of anti-tumor necrosis factor therapy.
AB  - OBJECTIVE: Androgens such as dehydroepiandrosterone sulfate (DHEAS) and
      testosterone are markedly lower in postmenopausal women with rheumatoid arthritis
      (RA) than in controls. In contrast, compared to controls, serum levels of
      estrogens are normal or elevated in women with RA. Since tumor necrosis factor
      (TNF) alters production of these hormones, we investigated changes of these
      hormones during anti-TNF antibody (anti-TNF) therapy with adalimumab in
      longstanding RA. METHODS: In this longitudinal anti-TNF therapy study in 13
      patients with long-standing RA without prior prednisolone (7 infusions of anti
      TNF: Week 0, 2, 4, 6, 8, 10, and 12), we measured serum concentrations of
      interleukin 6 (IL-6), androstenedione, DHEA, DHEAS, free testosterone, estrone,
      and 17ss-estradiol. Levels of these hormones in patients were compared to serum
      levels of 31 age and sex matched healthy controls. RESULTS: Upon treatment with
      anti-TNF, there was an impressive decrease of clinical markers of inflammation,
      erythrocyte sedimentation rate, and serum levels of IL-6. Serum levels of DHEAS
      and free testosterone were markedly lower at baseline in patients compared to
      controls, but this did not change during anti-TNF therapy. Serum levels of DHEA
      and 17ss-estradiol were significantly elevated in patients compared to controls,
      but similarly, anti-TNF therapy did not change initially increased levels. Molar
      ratios of hormones, which reflect hormone shifts via converting enzymes, showed
      typical alterations at baseline, but did not change markedly during anti-TNF
      therapy. CONCLUSION: Longterm therapy with anti-TNF did not change altered serum
      levels of typical sex hormones in patients with RA, although baseline values were
      largely different. In patients with RA, this indicates that alterations of sex
      hormones and altered activity of respective converting enzymes are imprinted for
      a long-lasting period over at least 12 weeks.

PMID- 15996061
TI  - Falsely elevated cardiac troponin-I in patients with seropositive rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine if patients with seropositive rheumatoid arthritis (RA)
      have abnormally elevated concentrations of cardiac troponin-I (cTnI). Reports
      suggest the presence of serum rheumatoid factor (RF) may interfere with the cTnI
      assay, leading to falsely elevated cTnI levels. One study reported a falsely
      elevated cTnI in 15 out of 100 serum samples with elevated RF using the Abbott
      assay, but no elevated level using the Bayer assay. It is unclear how many of
      these samples came from patients with RA. METHODS: Serum samples were drawn from
      60 patients with seropositive RA. We measured RF and cTnI levels using both the
      Abbott AxSYM assay and the Bayer ADVIA Centaur assay. RESULTS: Of 60 RA patients
      with RF ranging from 15 to 2724 IU/ml, none was found to have an elevated cTnI on
      either assay. CONCLUSION: Using 2 commercial assays for cTnI, we found that
      patients with seropositive RA do not have falsely elevated serum cTnI levels.

PMID- 15996062
TI  - Preliminary evaluation of a visual analog function scale for use in rheumatoid
      arthritis.
AB  - OBJECTIVE: Key outcomes in rheumatoid arthritis (RA) are evaluated with multi
      item ratings scales such as the Health Assessment Questionnaire (HAQ) and visual
      analog scales (VAS) such as pain and patient and physician global. As VAS scales
      are easy to use and particularly effective in research and patient care, we
      studied the characteristics, association, and psychometric properties of a VAS
      function scale (VAS-F) to determine if it could be used in RA studies and
      clinical practice. METHODS: A total of 394 patients with RA completed the HAQ,
      the HAQ-II, and a VAS functional scale. In addition, they completed standard
      assessments of pain, global, fatigue, sleep problems, joint count, and the
      Medical Outcome Study Short-Form 36 (SF-36) physical component summary score
      (PCS) and vitality and total pain scores. RESULTS: The HAQ-II was correlated with
      VAS-F at 0.76, but distributional characteristics of the HAQ and VAS-F differed,
      as the VAS-F scale results contained more higher scores as well as more lower
      scores compared with the HAQ-II and HAQ. Kendall's tau concordance analyses
      indicated that VAS scales were more concordant with other VAS than with non-VAS
      scales. Concordance of VAS-F was greatest with VAS global and was similar overall
      with VAS pain, sleep disturbance, fatigue, and quality of life. By contrast, the
      PCS, a multi-item scale, was more concordant with HAQ-II and HAQ. There was
      little to no difference between the VAS-F and the 2 HAQ with regard to
      concordance with the multi-item joint count, SF-36 vitality, and SF-36 total
      pain. CONCLUSION: The distribution differences between HAQ and HAQ-II and the VAS
      F suggest that patients do not see minor limitations as problematic, but rate
      major limitations as being particularly limiting and worthy of high ratings. A
      VAS functional scale represents a patient-weighted functional assessment in which
      additional interpretation is given to the meaning of the limitations by the
      patient. VAS-F scales may be suitable for use in the clinic and in research.
      However, studies to assess sensitivity to change are required to determine the
      appropriate role of this scale.

PMID- 15996063
TI  - Longitudinal fluctuation of antibodies to extractable nuclear antigens in
      systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the appearance, persistence, and disappearance of anti
      extractable nuclear antigen (ENA, Sm, U1-RNP, Ro/SSA, and La/SSB) and anti-native
      DNA (dsDNA) antibodies during systemic lupus erythematosus (SLE) followup.
      METHODS: One hundred and thirty patients who fulfilled American College of
      Rheumatology classification criteria for SLE with at least 5 yearly anti-ENA and
      dsDNA tests between 1987-2002 were retrospectively selected. Four longitudinal
      antibody data patterns were considered for each antibody: always absent, always
      present, absent at diagnosis with positive seroconversion, and present at
      diagnosis with negative seroconversion. RESULTS: Antibodies to Ro/SSA were
      present in 47%, U1-RNP in 36%, DNA in 32%, Sm in 23%, and La/SSB in 7% of
      patients. Among patients ever positive for a given autoantibody, the frequency of
      the "always present" pattern was 52% for anti-Ro/SSA, 38% for U1-RNP, 17% for Sm,
      11% for La/SSB, and 9% for DNA antibodies; the frequency of positive
      seroconversion was 56% for anti-La/SSB, 33% for DNA, 26% for Sm, 21% for U1-RNP,
      and 15% for Ro/SSA. Time to positive seroconversion varied from 1 to 8 years
      after diagnosis. Among patients with a positive test at diagnosis the frequency
      of those remaining positive between the 2nd and 4th year of followup decreased to
      39-78%, depending upon autoantibody specificity; between the 5th and 10th years
      this rate was 20-75%. Antibody data pattern frequency differed significantly
      among autoantibody specificities except between anti-U1-RNP and Ro/SSA (p = 0.15)
      and between anti-DNA and Sm antibodies (p = 0.29). CONCLUSION: The high frequency
      of longitudinal fluctuation in anti-ENA antibodies suggests that a periodic
      reappraisal may be appropriate in seronegative patients with a suspect diagnosis
      of SLE. The clinical significance of such fluctuation deserves future study.

PMID- 15996064
TI  - Prevalence of elevated pulmonary arterial pressures measured by echocardiography
      in a multicenter study of patients with systemic sclerosis.
AB  - OBJECTIVE: To estimate the prevalence of elevated pulmonary arterial pressures
      (PAP) as a correlate for pulmonary arterial hypertension (PAH) in patients with
      systemic sclerosis (SSc) in rheumatology centers in Canada. METHODS: During the
      one-year study period (June 2002-May 2003), charts of patients with SSc were
      reviewed to determine demographics, SSc characteristics, percentage of patients
      with a PAH diagnosis, and the site criteria for such diagnosis. Subjects with no
      PAH that had symptoms of dyspnea and/or fatigue were invited to undergo Doppler
      echocardiography to estimate their systolic PAP (sPAP). RESULTS: A total of 539
      patients with SSc (age 56 yrs +/- 13 SD, 84% female, 41% with diffuse SSc, 58%
      limited SSc, SSc disease duration 9 yrs +/- 7 SD) at 8 rheumatology centers were
      reviewed. Twenty-three percent of patients were diagnosed with elevated sPAP
      based on the site diagnosis criteria (i.e., > 30 mm Hg or > 35 mm Hg). From the
      non-PAH, not recently screened patients that had symptoms of dyspnea or fatigue,
      a total of 89 patients underwent a Doppler echocardiograph; 40% had sPAP > 35 mm
      Hg. CONCLUSION: Elevated PAP are common in both limited and diffuse SSc disease,
      occurring in 21% of limited and 26% of diffuse SSc patients. During the screening
      most patients had mild PAP elevations that would require further assessments such
      as right heart catheterization to diagnose PAH where appropriate. A high index of
      suspicion is important and routine echocardiography in symptomatic patients may
      allow earlier diagnosis of PAH and intervention. The proportion of SSc patients
      with mild to moderate elevations of PAP who will develop significant PAH is
      unknown and longterm studies are needed to address the natural progression.

PMID- 15996065
TI  - Temporal artery biopsy for giant cell arteritis.
AB  - OBJECTIVE: To evaluate the influence of temporal artery biopsy (TAB) techniques
      on establishing a diagnosis of giant cell arteritis (GCA). METHODS: A
      retrospective review of 141 TAB pathology records from 1996 to 2002 was
      conducted. Histopathology slides on 136 TAB were reviewed by a single,
      independent, blinded pathologist. RESULTS: The population included 101 (71.6%)
      women, mean age 75.8 years (range 45-92), and 40 men, mean age 73.9 years (range
      47-90). The mean length of a TAB sample after formalin fixation was 1.76 cm
      (range 0.1-5.3). Surgeons performing the TAB represented 6 disciplines.
      Ophthalmologists had the largest volume, at 78 biopsies (55.3%), and the longest
      segments of artery, with a mean length of 2.37 cm (range 0.4-5.3) (p < 0.001).
      Comparison of biopsy interpretation provided a kappa coefficient of 0.8 (95% CI
      0.69, 0.91). The 38 (27%) positive biopsies had a mean length of 2.07 cm (SD
      1.1), and the 98 negative biopsies a mean length of 1.69 cm (SD 1.04) (p =
      0.058). Biopsies < 1.0 cm length (n = 35, 25.7%) were less likely to be positive
      than those > or = 1.0 cm (p = 0.037). No significant differences in surgical
      discipline, hospital site, number of slides, or cross-sections/cm artery were
      found between the positive and negative biopsies. CONCLUSION: Biopsy specimens
      reported positive for GCA tended to be longer than those reported as negative. A
      "threshold" size of 1.0 cm is associated with increased diagnostic yield. Lack of
      standardization of biopsy harvesting and processing techniques may contribute to
      variable sensitivity of TAB.

PMID- 15996066
TI  - Diagnostic and management trends of giant cell arteritis: a physician survey.
AB  - OBJECTIVE: Opinions regarding diagnostic and treatment issues in giant cell
      arteritis (GCA) vary widely, yet few controlled trials exist to address these
      issues. Our objective was to compare espoused clinical policies regarding
      diagnosis and treatment of GCA among physicians involved in GCA care. METHODS:
      Utilizing professional society directories, US physicians were randomly selected
      to receive an 11-question survey. One hundred surveys were mailed to each of the
      following: family medicine, general internal medicine, general/vascular surgery,
      neurology, ophthalmology, otolaryngology, and rheumatology. Data were analyzed
      according to specialty and specialty group: rheumatology, medical specialties
      (family medicine, general internal medicine, neurology), and surgical specialties
      (general/vascular, ophthalmology, and otolaryngology). RESULTS: The percentage of
      surveys returned was 34.7%. Analysis was limited to the 79% participating in at
      least one aspect of GCA care. Greater than 90% of respondents believe that
      temporal arteritis biopsy (TA Bx) should be performed in all suspected cases of
      GCA. Eighty-five percent of rheumatology believe TA Bx is indicated even when
      pretest probability of GCA is high, compared to 65% of medical specialties (p =
      0.03). Eighty percent of rheumatology believe steroid usage decreases the yield
      of TA Bx, compared to 62% of surgical specialties (p = 0.04). When initial TA Bx
      is negative, medical specialties (26%) and surgical specialties (31%) were more
      likely than rheumatology (5%) to decline contralateral biopsy, even if the
      contralateral side is symptomatic (p = 0.04 and 0.01, respectively). CONCLUSION:
      Considerable variation exists regarding key elements of diagnosis and treatment
      in the evaluation of suspected GCA. The morbidity of GCA and the potential
      toxicity of therapy highlights the need for controlled trials to address these
      issues.

PMID- 15996067
TI  - Bone loss is detected more frequently in patients with ankylosing spondylitis
      with syndesmophytes.
AB  - OBJECTIVE: To define the relationship between bone growth (syndesmophytes) and
      bone loss (osteoporosis) in ankylosing spondylitis (AS). METHODS: Bone mineral
      density (BMD) at the spine, hip, and radius was measured by dual-energy x-ray
      absorptiometry (DEXA), dual-energy quantitative computed tomography (DEQCT), and
      peripheral quantitative computed tomography (pQCT) in 103 patients with AS.
      Radiographs of the lumbar spine were used to detect syndesmophytes. Patients were
      divided in 3 groups according to disease duration. RESULTS: Osteopenia at the hip
      and spine was found by DEXA in 56% and 41%, respectively, of the patients with
      disease duration < 5 years (n = 27), with an additional 11% and 15% having
      osteoporosis. In patients with a longer disease duration, > 10 years (n = 28),
      29% were osteoporotic at the hip and only 4% at the lumbar spine. In contrast,
      using spinal DEQCT, 59% of patients with early disease were found to be
      osteopenic; 36% of patients with long-standing disease were osteopenic and 18%
      were osteoporotic. More than half the patients (55%) had syndesmophytes (n = 55).
      With spinal DEQCT there were more patients with syndesmophytes (63%) in the group
      with reduced bone density than in the group without (45%). This was similar with
      DEXA measurements at the hip, where 31% compared to 14% had osteoporosis,
      respectively. Osteocalcin was elevated in 34% of patients, but was not associated
      with disease activity or BMD. CONCLUSION: The majority of patients with AS had
      reduced bone density. The method of bone density measurement is critical and
      should be different depending on disease duration. The finding that more patients
      with syndesmophytes had reduced bone density than those without suggests that
      bone growth and bone loss occur in parallel, and the role of inflammation in this
      process warrants further investigation.

PMID- 15996068
TI  - Human immunodeficiency virus related reactive arthritis in Zambia.
AB  - OBJECTIVE: To characterize the clinical, radiological, and diagnostic features of
      reactive arthritis (ReA) in indigenous Black Zambians with human immunodeficiency
      virus (HIV) infection. METHODS: Consecutive patients attending an arthritis
      clinic over a 5-year period were studied prospectively. Those who satisfied
      diagnostic criteria for ReA were analyzed. RESULTS: In total, 170 patients
      satisfied the ESSG criteria for ReA; 71 (45 men, 26 women) had one or more
      extraarticular manifestations; 30% had enteroreactive and 14% uroreactive
      disease. Only 59% of patients had the diagnostic features of ReA at presentation.
      The initial diagnosis was undifferentiated spondyloarthropathy (uSpa) in 20%,
      other ReA in 14%, and "arthritis alone" in 7%. Of 65 (42 men, 23 women) patients
      tested, 94% were HIV-positive (91% men, 100% women). In those with HIV, the
      arthritis was predominantly polyarticular, lower limb-predominant, and
      progressive; 58% of 33 with persistent disease had erosions of foot and/or hand
      joints (average disease duration, 24.4 mo); 6 of 10 showed early radiological
      spine or sacroiliac joint changes (average duration 47.7 mo). Anterior uveitis
      occurred in 33% of patients, while keratoderma blenorrhagicum and stomatitis
      occurred in 14.3% and 9.5%, respectively, of patients with enteroreactive ReA.
      Uroreactive ReA was more common in women. There were no significant differences
      in the clinical, diagnostic, or radiographic features between men and women or
      between those with or without a known preceding trigger. CONCLUSION: HIV
      associated ReA in Black Zambians frequently follows an accelerated course with a
      strong tendency to relapse, develop early erosions and joint deformity, and
      become chronic. The clinical, diagnostic, and radiographic features are
      indistinguishable from those described in the conventional (HLA-B27 related)
      disease, although our HIV-positive patients have a high overall frequency of
      uveitis, keratoderma, and onycholysis.

PMID- 15996069
TI  - Intraarticular corticosteroid injection for first carpometacarpal osteoarthritis.
AB  - OBJECTIVE: To evaluate the efficacy of intraarticular corticosteroid injections
      for osteoarthritis (OA) of the first carpometacarpal (CMC) joint. METHODS: This
      was a prospective case series of patients presenting to a community rheumatology
      clinic with OA of the 1st CMC joint. A total of 0.25 ml of methylprednisolone
      acetate was injected into the 1st CMC joint in 25 patients, who were followed for
      one year. RESULTS: A significant improvement in the visual analog scale (VAS) for
      pain was noted at one month but not at 3, 6, or 12 months postinjection. However,
      5 patients were pain-free at 12 months postinjection. Many patients noted
      improvement in tasks such as lifting a full cup and turning a faucet. Injections
      were well tolerated, with only 2 patients noting minor side effects. CONCLUSION:
      These results suggest that intraarticular corticosteroid injection for 1st CMC OA
      is a well tolerated procedure. A significant longterm benefit of corticosteroid
      injection for 1st CMC OA was not observed.

PMID- 15996071
TI  - Safety study of intraarticular injection of interleukin 1 receptor antagonist in
      patients with painful knee osteoarthritis: a multicenter study.
AB  - OBJECTIVE: Interleukin 1 (IL-1) plays a pivotal role in the pathogenesis of
      osteoarthritis (OA). In animal models of OA, IL-1 blockade by IL-1 receptor
      antagonist (IL-1Ra) can slow the progression of disease. We examined the safety
      of intraarticular (IA) injections of recombinant human IL-1Ra in patients with
      knee OA. METHODS: A prospective multicenter trial was conducted using the
      continual reassessment method. Six doses were considered, 0.05 mg up to 150 mg IL
      1Ra, and the trial was double-blind regarding the dose administered. Patients
      with symptomatic knee OA and without synovial fluid effusion were included. Acute
      inflammatory reaction (the primary endpoint defining intolerance) was recorded if
      pain increase over 30 mm on 100 mm visual analog scale and synovial fluid
      effusion occurred within 72 h after the IA injection. As a secondary aim,
      efficacy was estimated (by total pain and Western Ontario and McMaster University
      OA functional index) until Month 3. RESULTS: One patient received 0.05 mg and 13
      patients received 150 mg of IL-1Ra. No acute reaction occurred (one patient
      experienced postinjection joint swelling with no pain) and the 150 mg dose was
      considered the maximum tolerated dose (intolerance level 0%; confidence interval
      0, 9.1%). A significant improvement was still observed until Month 3 in the 13
      patients who received 150 mg IL-1Ra: pain improved by -20.4 +/- 23.3 mm (p =
      0.008) and WOMAC global score by -19.5 +/- 20.1 (p = 0.005). CONCLUSION: IA
      injection of IL-1Ra in patients with knee OA was well tolerated and did not
      induce any acute inflammatory reaction. The feasibility of such IA injections of
      IL-1Ra opens a promising therapeutic perspective for patients with OA.

PMID- 15996070
TI  - Role of interleukin 6 (IL-6)/IL-6R-induced signal tranducers and activators of
      transcription and mitogen-activated protein kinase/extracellular.
AB  - OBJECTIVE: Studies have described elevated levels of interleukin 6 (IL-6) and its
      soluble receptor (sIL-6R) in osteoarthritic and rheumatoid joints, as well as the
      inhibitory effect of this combination on cartilage matrix production. We
      investigated the ability of IL-6/sIL-6R to modulate gene expression of matrix
      metalloproteinase (MMP) and ADAMTS (ADAMS with thrombospondin motifs) family
      members in bovine chondrocytes, and the potential role of signal transducers and
      activators of transcription (STAT) and mitogen-activated protein kinases (MAPK)
      in this regulation. METHODS: Primary cultures of bovine chondrocytes were
      stimulated with IL-6/sIL-6R for 30 min (Western blot and EMSA) or 24 h (RNA
      measurements) in the presence or absence of the STAT inhibitor parthenolide or
      the MAPK inhibitor PD 098059. mRNA was assessed by RT-PCR for the expression of
      MMP (MMP-1, -3, and -13) and 2 ADAMT family members (ADAMTS-4 and -5/11).
      RESULTS: IL-6/sIL-6R markedly induced activation of STAT and extracellular signal
      related kinase (ERK1/2) and the subsequent expression of the collagenases MMP-1
      and MMP-13 as well as MMP-3, an aggrecan-degrading enzyme and activator of pro
      MMP. Expression of the 2 specific aggrecanases ADAMTS-4 and -5/11 was also
      elevated by this combination. Both STAT and MAPK signaling pathways were found to
      contribute to the IL-6/sIL-6R induction mechanisms, the overall effect being
      dependent on the respective magnitude of response and the crosstalk between the 2
      pathways. CONCLUSION: These data indicate that the cartilage-degrading properties
      of IL-6/sIL-6R are mediated by induction of the aggrecan-degrading enzymes ADAMTS
      4, -5/11, and MMP-3, and the collagen-degrading enzymes MMP-1 and -13. STAT and
      MAPK pathways play a crucial role in IL-6/sIL-6R modulation of these enzymes,
      suggesting that new strategies in the treatment of osteoarticular diseases might
      target these transduction cascades.

PMID- 15996072
TI  - The factor subdimensions of the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) help to specify hip and knee osteoarthritis. a
      prospective evaluation and validation study.
AB  - OBJECTIVE: To determine whether it is possible to specify different score
      patterns for hip and knee osteoarthritis (OA), and to identify the degree of
      responsiveness and the validity of the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) factors, which are alternative health dimensions
      obtained by factor analysis of the WOMAC items. METHODS: WOMAC scales and WOMAC
      factors were compared in a prospective setting examining patients with hip and
      knee OA before and after rehabilitative inpatient intervention (n = 317). In a
      partial sample (n = 103), the validity of the WOMAC factors was determined by a
      global rating of their activities. RESULTS: The WOMAC factor
      "ascending/descending" was significantly different for hip and knee OA in the
      health state before therapy (score in hip 5.09, in knee 6.59; p < 0.001); this
      was also true of the effect size after therapy (hip 0.39, knee 0.65; p = 0.012).
      The WOMAC scales did not differ for the 2 conditions. The WOMAC factor
      "ascending/descending" was the most responsive dimension in knee OA (effect size
      0.65), but in hip OA the WOMAC pain scale was most responsive (effect size 0.55).
      Most of the WOMAC factors correlated moderately (r = 0.52-0.69) with the
      patient's self-rating on the validation questionnaire. CONCLUSION: The WOMAC
      factors are valid measures. Analyzing the WOMAC by the WOMAC factors facilitates
      and improves the differential relevance and accuracy of the WOMAC for specific
      conditions such as hip and knee OA.

PMID- 15996073
TI  - Translation and validation of the Turkish version of the arthritis impact
      measurement scales 2 in patients with knee osteoarthritis.
AB  - OBJECTIVE: To translate and evaluate the validity, reliability, and acceptability
      of Arthritis Impact Measurement Scales 2 (AIMS2) in patients with knee
      osteoarthritis (OA). METHODS: Turkish AIMS2 was developed using the "translation
      backward translation" method and administered to 141 patients with symptomatic
      knee OA. Reliability was assessed by test-retest and internal consistency
      analyses. Construct validity was assessed by correlating the AIMS2 scales with
      Western Ontario and McMaster University Osteoarthritis Index (WOMAC), 100 mm
      visual analog scale (VAS) for pain, patient's and physician's global assessment,
      range of motion (ROM), and Kellgren-Lawrence grading system. RESULTS: Test-retest
      reliability coefficients ranged from 0.75-0.98, and Cronbach's alpha coefficients
      from 0.72-0.90. Significant moderate to high correlations were obtained between
      AIMS2 scales (except social activities and support from family and friends
      scales) and most of the other clinical measurements. CONCLUSION: Turkish AIMS2 is
      a valid, reliable, and acceptable instrument in patients with symptomatic knee
      OA.

PMID- 15996074
TI  - A randomized controlled trial of dehydroepiandrosterone in postmenopausal women
      with fibromyalgia.
AB  - OBJECTIVE: Patients with fibromyalgia (FM) consistently have adrenal
      hyporesponsiveness and low dehydroepiandrosterone (DHEA) levels. DHEA is promoted
      for and used by patients with FM. We tested the efficacy and safety of DHEA
      supplementation in ameliorating the symptoms of FM. METHODS: In a double-blind
      crossover study, postmenopausal women with FM were randomized to DHEA
      supplementation (50 mg/day) or placebo for 3 months, with a one-month washout
      period in between. Patients were assessed monthly for well-being and pain and by
      medical evaluations at the beginning and the end of each treatment period. The
      primary outcome was well being; secondary outcomes were pain, fatigue, cognition,
      sexuality, functional impairment, depression, and anxiety. RESULTS: A total of 52
      patients were randomized, 47 patients completed the DHEA treatment period, and 45
      the placebo treatment period. After 3 months of treatment with 50 mg of DHEA,
      median DHEA sulfate blood levels had tripled, but there was no improvement in
      well-being, pain, fatigue, cognitive dysfunction, functional impairment,
      depression, or anxiety, nor in objective measurements made by physicians.
      Androgenic side effects (greasy skin, acne, and increased growth of body hair)
      were more common during the DHEA treatment period (p = 0.02). CONCLUSION: DHEA
      does not improve quality of life, pain, fatigue, cognitive function, mood, or
      functional impairment in FM.

PMID- 15996075
TI  - Is chronic widespread pain a predictor of all-cause morbidity? A 3 year
      prospective population based study in family practice.
AB  - OBJECTIVE: To investigate whether chronic widespread pain predicts illness seen
      in general practice in a 3 year followup period. METHODS: A postal questionnaire
      was conducted in an adult family practice population sample of 3968, and there
      were 2606 responders (66%). From the 2296 responders who consented to their
      record review, we identified 184 subjects with chronic widespread pain and
      assessed their outcome based on the first recorded morbidity within each of 15
      categories during a 3 year followup period of computerized family practice
      records. Psychological distress at baseline was also measured using the Hospital
      Anxiety and Depression scale. RESULTS: Of the survey responders, 2089 subjects
      (91%) completed the full 3 year followup period. Out of the 15 main morbidity
      categories examined, 11 were associated with pain status at baseline. The
      strongest associations between chronic widespread pain at baseline and subsequent
      morbidity, adjusted for age, sex, and social deprivation, were for
      musculoskeletal (MSK) disorders (rate ratio 4.36; 95% confidence interval 3.2
      5.9), accidents (2.46; 95% CI 1.2-5.1), mental health disorders (2.24; 95% CI 1.5
      3.3), dermatological disorders (2.16; 95% CI 1.6-2.9), and infections (1.96; 95%
      CI 1.3-2.9). Controlling for psychological distress reduced the strength of
      associations between chronic widespread pain and future morbidity, but 9 of the
      11 were still statistically significant. In the 3 year followup period, an
      estimated 7.7% of all non-MSK and 12.6% of all MSK morbidity consultations were
      related to chronic widespread pain as reported at baseline. CONCLUSION: People
      who report chronic widespread pain subsequently consult more frequently about non
      MSK and MSK problems than people with no pain, and this is not explained by
      psychological distress. The overall impact on healthcare use is substantial. Our
      study provides more evidence for overlap and links between morbidities that may
      be part of a larger pathological or somatization syndrome.

PMID- 15996076
TI  - Elevated concentrations of monocyte derived cytokines in synovial fluid of
      children with enthesitis related arthritis and polyarticular types of juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: Cytokines are the major mediators of joint damage in chronic
      arthritis. Data on synovial fluid (SF) cytokine concentrations in patients with
      juvenile idiopathic arthritis (JIA), especially enthesitis related arthritis
      (ERA), are limited. We measured levels of different monocyte derived cytokines, T
      cell derived cytokines, and a proinflammatory chemokine in SF specimens from
      children with ERA or polyarticular (Poly) rheumatoid factor (RF)-negative JIA.
      METHODS: Macrophage products [tumor necrosis factor-a (TNF-a), interleukin 1ss
      (IL-1ss), IL-6, IL-12p40)], T lymphocyte products [IL-2, IL-4, interferon-g (IFN
      g)], and a proinflammatory chemokine (IL-8) were assayed using ELISA in SF
      specimens from 53 patients with JIA [ERA 34, polyarticular RF-negative 19] and 40
      patients with rheumatoid arthritis (RA). RESULTS: In the ERA group, median SF
      cytokine levels were higher compared to RA (all values are pg/ml): IL-1ss [< 15.6
      (< 15.6-213) vs < 15.6 (< 15.6-41); p < 0.01], IL-12p40 [236 (< 15.6-1714) vs 21
      (< 15.6-520); p < 0.0001], and IL-6 [1139 (< 4.6-2187) vs 835 (< 4.6-875); p <
      0.0001]. TNF-a and IFN-g levels were similar to RA. IL-8 levels were
      significantly less than RA (p < 0.0001). The median levels of IL-1ss [39.4 (<
      15.6-558) vs < 15.6 (< 15.6-41); p < 0.0001] and IL-12p40 [209 (< 15.6-849) vs 21
      (< 15.6-520); p < 0.0001] were higher in patients with Poly-JIA compared to RA.
      TNF-a, IL-6, and IL-8 levels in Poly-JIA were comparable to RA. IL-2 and IL-4
      were not detectable in any patient with JIA. Cytokine profile comparison between
      the 2 subsets revealed that the median IL-6 [1139 (< 4.6-2187) vs 790 (17.4
      2119); p < 0.01] and IFN-g levels [235 (< 4.6-600) vs < 4.6 (< 4.6-412); p <
      0.0001] were higher in ERA than in Poly-JIA. In contrast, median IL-8 levels were
      higher in Poly-JIA [200 (3.8-200)] compared to ERA [74.6 (4-200); p < 0.001].
      However, there was no difference in levels of TNF-a, IL-1ss, and IL-12p40 between
      patients with these 2 subtypes of JIA. CONCLUSION: SF levels of IL-1ss and IL
      12p40 are increased in both Poly-JIA and ERA as compared to RA. IL-6 levels were
      higher in ERA compared to RA. Levels of TNF-a were comparable to RA in both Poly
      JIA and ERA. This suggests that joint inflammation in JIA is mediated
      predominantly by monocytes. In ERA the levels of IL-6 and IFN-g are higher than
      in Poly-JIA. The increase in IFN-g in children with ERA with undetectable IL-4
      suggests a Th1-dominant immune response in this disease subset.

PMID- 15996077
TI  - Decreased bone speed of sound in children with growing pains measured by
      quantitative ultrasound.
AB  - OBJECTIVE: The most common cause of recurring childhood musculoskeletal pain is
      termed growing pains (GP). We hypothesized that GP may represent a local overuse
      syndrome and therefore may be associated with decreased bone speed of sound (SOS)
      measured by quantitative ultrasound (US). METHODS: We studied 39 children with
      GP. Bone SOS was measured by US in both mid-tibial and radius bones according to
      a validated protocol. Unpaired Student t test was used to compare patients and
      norms of healthy controls. RESULTS: Tibial SOS was significantly reduced in
      children with GP compared to controls (Z score -0.546 for boys and -0.891 for
      girls; p = 0.004, p < 0.001, respectively). Radius SOS was significantly reduced
      only in girls with GP (Z score -0.692, p = 0.006). No correlation was found
      between bone SOS and various demographic and clinical factors besides the child's
      ethnicity and body mass index. CONCLUSION: Bone SOS was significantly reduced in
      children with GP, especially in painful tibial regions. GP may represent a local
      overuse syndrome.

PMID- 15996080
TI  - Ossification of the posterior longitudinal ligament of the cervical spine and
      SAPHO syndrome.
AB  - We describe a case of cervical cord compression due to ossification of the
      posterior longitudinal ligament of the spine (OPLLS) in a 43-year-old Vietnamese
      patient with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and
      osteitis). Idiopathic OPLLS is mainly reported in 50- to 60-year-old men,
      particularly in Japanese, with a prevalence of 2%. Cervical myelopathy may occur.
      In addition to OPLLS in patients of Asian origin, the condition has also been
      described in association with ossifying diseases, including ankylosing
      spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) but not
      previously, to our knowledge, with SAPHO syndrome.

PMID- 15996081
TI  - Systemic lupus erythematosus presenting with features suggestive of human
      immunodeficiency virus infection.
AB  - We describe 8 patients who presented with fever, weight loss, anemia, and oral
      and/or esophageal candidiasis, and who were initially thought to have human
      immunodeficiency virus (HIV) infection or lymphoma. These patients fulfilled
      American College of Rheumatology criteria for systemic lupus erythematosus (SLE)
      because of arthralgias or arthritis, hematological derangements, and
      immunological abnormalities. Treatment was delayed because SLE did not
      immediately enter into the differential diagnosis. All patients had a rapid
      response to corticosteroids, with defervescence of fever, decrease in
      lymphadenopathy within 24-48 hours, and complete resolution of lymphadenopathy
      and other signs and symptoms of illness in 7-10 days. It is important to
      recognize this mode of SLE presentation in patients who test negative for HIV
      infection so that the appropriate diagnostic evaluation and initiation of
      treatment can be expedited.

PMID- 15996082
TI  - Efficacy of rituximab in refractory polymyositis.
AB  - We describe the effectiveness of rituximab, an anti-B lymphocyte monoclonal
      antibody, in a case of refractory polymyositis with interstitial pulmonary
      disease and anti-Jo-1 autoantibody (antisynthetase syndrome). Rituximab was well
      tolerated, and its efficacy in inflammatory myositis should be evaluated.

PMID- 15996083
TI  - Refractory polyarteritis nodosa successfully treated with infliximab.
AB  - We describe a woman with severe polyarteritis nodosa (PAN) with visceral
      involvement unresponsive to multiple immunosuppressive drugs. Infliximab
      treatment was very effective in this case. Infliximab may potentially be used as
      an alternative agent for the treatment of patients with PAN refractory to
      conventional therapy.

PMID- 15996084
TI  - Treatment of orbital myositis with adalimumab (Humira).
AB  - Adalimumab is a fully humanized IgG1 monoclonal antibody to tumor necrosis factor
      a. We describe 2 patients (17 and 13 years of age) with refractory, steroid
      dependent, recurrent nonspecific orbital myositis not controlled with standard
      immunosuppressive medications. Both improved with adalimumab treatment, allowing
      reduction in corticosteroid dosage without disease flare.

PMID- 15996085
TI  - Chronic diffuse sclerosing osteomyelitis treated with risedronate.
AB  - We describe a 21-year-old woman with chronic diffuse sclerosing osteomyelitis
      (CDSO) of the left femur. The patient presented with shortening of the left leg
      and intractable pain that was unrelieved with conventional analgesia.
      Radiological imaging and open bone biopsy confirmed the diagnosis of chronic
      diffuse sclerosing osteomyelitis. Treatment with risedronate was commenced and a
      dramatic response in the patient's symptoms and biochemical markers of bone
      turnover was observed. To our knowledge this is the first case of CDSO treated
      successfully with risedronate.

PMID- 15996086
TI  - Usefulness of plain film radiography in the diagnosis of dactylitis by history
      taking.

PMID- 15996088
TI  - Reactions to infliximab in patients with rheumatoid arthritis.

PMID- 15996090
TI  - Reactions to infliximab in patients with rheumatoid arthritis.

PMID- 15996092
TI  - Bioavailability of higher dose MTX comparing oral and subcutaneous administration
      in patients with RA.

PMID- 15996093
TI  - Treatment of relapsing polychondritis with a TNF antagonist.

PMID- 15996094
TI  - Monomeric G-protein-coupled receptor as a functional unit.
AB  - Rhodopsin, the first purified G-protein-coupled receptor (GPCR), was
      characterized as a functional monomer 30 year ago, but dimerization of GPCRs
      recently became the new paradigm of signal transduction. It has even been
      claimed, on the basis of recent biophysical and biochemical studies, that this
      new concept could be extended to higher-order oligomerization. Here this view is
      challenged. The new studies of rhodopsin and other simple (class 1a) GPCRs
      solubilized in detergent are re-assessed and are compared to the earlier
      classical studies of rhodopsin and other membrane proteins solubilized in
      detergent. The new studies are found to strengthen rather than invalidate the
      conclusions of the early ones and to support a monomeric model for rhodopsin and
      other class 1a GPCRs. A molecular model is proposed for the functional coupling
      of a rhodopsin monomeric unit with a G-protein heterotrimer. This model should be
      valid even for GPCRs that exist as structural dimers.

PMID- 15996095
TI  - Catalytic cycling in beta-phosphoglucomutase: a kinetic and structural analysis.
AB  - Lactococcus lactis beta-phosphoglucomutase (beta-PGM) catalyzes the
      interconversion of beta-d-glucose 1-phosphate (beta-G1P) and beta-d-glucose 6
      phosphate (G6P), forming beta-d-glucose 1,6-(bis)phosphate (beta-G16P) as an
      intermediate. Beta-PGM conserves the core domain catalytic scaffold of the
      phosphatase branch of the HAD (haloalkanoic acid dehalogenase) enzyme
      superfamily, yet it has evolved to function as a mutase rather than as a
      phosphatase. This work was carried out to identify the structural basis
      underlying this diversification of function. In this paper, we examine beta-PGM
      activation by the Mg(2+) cofactor, beta-PGM activation by Asp8 phosphorylation,
      and the role of cap domain closure in substrate discrimination. First, the 1.90 A
      resolution X-ray crystal structure of the Mg(2+)-beta-PGM complex is examined in
      the context of previously reported structures of the Mg(2+)-alpha-d-galactose-1
      phosphate-beta-PGM, Mg(2+)-phospho-beta-PGM, and Mg(2+)-beta-glucose-6-phosphate
      1-phosphorane-beta-PGM complexes to identify conformational changes that occur
      during catalytic turnover. The essential role of Asp8 in nucleophilic catalysis
      was confirmed by demonstrating that the D8A and D8E mutants are devoid of
      catalytic activity. Comparison of the ligands to Mg(2+) in the different
      complexes shows that a single Mg(2+) coordination site must alternatively
      accommodate water, phosphate, and the phosphorane intermediate during catalytic
      turnover. Limited involvement of the HAD family metal-binding loop in Mg(2+)
      anchoring in beta-PGM is consistent with the relatively loose binding indicated
      by the large K(m) for Mg(2+) activation (270 +/- 20 microM) and with the
      retention of activity found in the E169A/D170A double loop mutant. Comparison of
      the relative positions of cap and core domains in the different complexes
      indicated that interaction of cap domain Arg49 with the "nontransferring"
      phosphoryl group of the substrate ligand might stabilize the cap-closed
      conformation, as required for active site desolvation and alignment of Asp10 for
      acid-base catalysis. Kinetic analyses of the specificity of beta-PGM toward
      phosphoryl group donors and the specificity of phospho-beta-PGM toward phosphoryl
      group acceptors were carried out. The results support a substrate induced-fit
      mechanism of beta-PGM catalysis, which allows phosphomutase activity to dominate
      over the intrinsic phosphatase activity. Last, we present evidence that the
      autophosphorylation of beta-PGM by the substrate beta-G1P accounts for the origin
      of phospho-beta-PGM in the cell.

PMID- 15996096
TI  - Structural basis for tumor pyruvate kinase M2 allosteric regulation and
      catalysis.
AB  - Four isozymes of pyruvate kinase are differentially expressed in human tissue.
      Human pyruvate kinase isozyme M2 (hPKM2) is expressed in early fetal tissues and
      is progressively replaced by the other three isozymes, M1, R, and L, immediately
      after birth. In most cancer cells, hPKM2 is once again expressed to promote tumor
      cell proliferation. Because of its almost ubiquitous presence in cancer cells,
      hPKM2 has been designated as tumor specific PK-M2, and its presence in human
      plasma is currently being used as a molecular marker for the diagnosis of various
      cancers. The X-ray structure of human hPKM2 complexed with Mg(2+), K(+), the
      inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate (FBP)
      has been determined to a resolution of 2.82 A. The active site of hPKM2 is in a
      partially closed conformation most likely resulting from a ligand-induced domain
      closure promoted by the binding of FBP. In all four subunits of the enzyme
      tetramer, a conserved water molecule is observed on the 2-si face of the
      prospective enolate and supports the hypothesis that a proton-relay system is
      acting as the proton donor of the reaction (1). Significant structural
      differences among the human M2, rabbit muscle M1, and the human R isozymes are
      observed, especially in the orientation of the FBP-activating loop, which is in a
      closed conformation when FBP is bound. The structural differences observed
      between the PK isozymes could potentially be exploited as unique structural
      templates for the design of allosteric drugs against the disease states
      associated with the various PK isozymes, especially cancer and nonspherocytic
      hemolytic anemia.

PMID- 15996097
TI  - Biochemical and structural characterization of a novel class of inhibitors of the
      type 1 insulin-like growth factor and insulin receptor kinases.
AB  - The type 1 insulin-like growth factor receptor (IGF-1R) is often overexpressed on
      tumor cells and is believed to play an important role in anchorage-independent
      proliferation. Additionally, cell culture studies have indicated that IGF-1R
      confers increased resistance to apoptosis caused by radiation or chemotherapeutic
      agents. Thus, inhibitors of the intracellular kinase domain of this receptor may
      have utility for the clinical treatment of cancer. As part of an effort to
      develop clinically useful inhibitors of IGF-1R kinase, a novel class of pyrrole-5
      carboxaldehyde compounds was investigated. The compounds exhibited selectivity
      against the closely related insulin receptor kinase intrinsically and in cell
      based assays. The inhibitors formed a reversible, covalent adduct at the kinase
      active site, and treatment of such adducts with sodium borohydride irreversibly
      inactivated the enzyme. Analysis of a tryptic digest of a covalently modified IGF
      1R kinase fragment revealed that the active site Lys1003 had been reductively
      alkylated with the aldehyde inhibitor. Reductive alkylation of the insulin
      receptor kinase with one of these inhibitors led to a similarly inactivated
      enzyme which was examined by X-ray crystallography. The crystal structure
      confirmed the modification of the active site lysine side chain and revealed
      details of the key interactions between the inhibitor and enzyme.

PMID- 15996098
TI  - Mutation of the adenylylated tyrosine of glutamine synthetase alters its
      catalytic properties.
AB  - Glutamine synthetase is central to nitrogen metabolism in the Gram-negative
      bacteria. The amount of glutamine synthetase in the cell and its catalytic
      activity are tightly regulated by multiple, sophisticated mechanisms. Reversible
      covalent modification of Tyr-397 is central to the regulation of glutamine
      synthetase activity, via esterification of the hydroxyl group to AMP in a process
      termed adenylylation. As expected, site-specific mutation of this surface-exposed
      Tyr-397 to Phe, Ala, or Ser was found to prevent adenylylation. Unexpectedly,
      these mutations had major effects on the catalytic characteristics of glutamine
      synthetase. The specific activities of each mutant were approximately doubled,
      the pH-activity profiles changed, and divalent-cation specificity was altered.
      Overall, Tyr397Phe behaved as if it were unadenylylated, while both Tyr397Ala and
      Tyr397Ser behaved as if they were adenylylated. Thus, subtle modifications in the
      environment of residue 397 are sufficient to induce changes previously thought to
      require adenylylation.

PMID- 15996099
TI  - Purification and biochemical characterization of a pyruvate-specific class II
      aldolase, HpaI.
AB  - HpaI, a class II pyruvate-specific aldolase involved in the catabolic pathway of
      hydroxyphenylacetate, is overexpressed and purified. A previous suggestion that
      phosphate is involved in proton transfer of pyruvate, based on the crystal
      structure of the homologous 2-dehydro-3-deoxygalactarate aldolase, is not
      substantiated from biochemical studies with HpaI. Thus, specific activities of
      the enzyme for the substrate 4-hydroxy-2-ketopentanoate in sodium HEPES and Tris
      acetate buffers are higher than in sodium phosphate buffer. The enzyme also
      catalyzed the partial reaction of pyruvate proton exchange with an initial rate
      of 0.77 mmol min(-)(1) mg(-)(1) in phosphate-free buffer, as monitored by nuclear
      magnetic resonance. Steady-state kinetic analysis shows that the enzyme is also
      able to catalyze the aldol cleavage of 4-hydroxy-2-ketohexanoate and 3-deoxy-d
      manno-oct-2-ulosonic acid (KDO). The enzyme exhibits significant oxaloacetate
      decarboxylase activity, with a k(cat) value 2.4-fold higher than the
      corresponding value for the aldol cleavage of 4-hydroxy-2-ketopentanoate. Sodium
      oxalate, an analogue of the enolate intermediate of the enzyme-catalyzed
      reaction, is a competitive inhibitor of the enzyme, with a K(i) value of 5.5
      microM. Replacement of an active site arginine residue (R70) with alanine by site
      specific mutagenesis resulted in an enzyme that lacks both aldolase and
      decarboxylase activities. The mutant enzyme is also unable to catalyze pyruvate
      proton exchange. The dissociation constant for pyruvate in the R70A mutant,
      determined by fluorescence titration, is similar to that of the wild-type enzyme,
      indicating that pyruvate binding is not affected by this mutation. Together, the
      results show that R70 influences catalysis in HpaI, particularly at the pyruvate
      proton exchange step.

PMID- 15996100
TI  - Kinetic studies of site-directed mutational isomalto-dextranase-catalyzed
      hydrolytic reactions on a 27 MHz quartz-crystal microbalance.
AB  - A quartz-crystal microbalance (QCM) technique was applied to analyze effects of
      site-directed mutagenesis of a glycosidase (isomalto-dextranase) on the
      hydrolysis mechanism of the substrate binding (k(on), k(off), and K(d)) and the
      catalytic process (k(cat)), separately, by using a dextran-immobilized QCM in
      buffer solution. D266N, D198N, and D313N mutants, which are predicted as critical
      residues of the isomalto-dextranase hydrolytic activity, dramatically decreased
      the apparent enzyme activity. The D266N mutant, however, did not change the
      substrate binding ability (K(d)), and the D198N and D313N mutants largely
      increased K(d) values due to the increase of k(off) and/or the decrease of k(on)
      values, as well as the negatively small k(cat) values. From these results, we
      estimate the reaction mechanism, in which Asp266 acts as only a general acid in
      the catalytic process, Asp198 acts as both nucleophile in the catalytic process
      and binding the substrate, and Asp313 acts as only the substrate binding.

PMID- 15996101
TI  - The modular structure of SIP facilitates its role in stabilizing multiprotein
      assemblies.
AB  - Siah-interacting protein (SIP) was identified as a novel adaptor that physically
      links the E3 ubiquitin ligase activity of Siah-1 with Skp1 and Ebi F-Box protein
      in the degradation of beta-catenin, a transcriptional activator of TCF/LEF genes.
      In this study, we have used solution NMR spectroscopy to characterize the domain
      structure of SIP, which includes a novel helical hairpin domain at the N-terminus
      flexibly linked to a CS domain and an unstructured carboxy terminal SGS domain.
      These studies have been complemented by mapping the sites of functionally
      important protein-protein interactions involving Siah-1 and Skp1 to individual
      domains of SIP. NMR-based chemical shift perturbation assays show that Siah-1
      interacts with the flexible linker between SIP N and CS domains. This site for
      interaction in the linker does not perturb residues in the structured region at
      the N-terminus but does appear to restrict the rotational freedom of the SIP CS
      domain in the context of the full-length protein. In contrast, Skp1 engages the
      SIP CS domain exclusively through weak interactions that are not coupled to the
      other domains. The principal role of the modular structure of SIP appears to be
      in bringing these two proteins into physical proximity and orchestrating the
      orientation required for polyubiquitination of beta-catenin in the intact SCF
      type complex.

PMID- 15996102
TI  - DNA cytosine C5 methyltransferase Dnmt1: catalysis-dependent release of
      allosteric inhibition.
AB  - We followed the cytosine C(5) exchange reaction with Dnmt1 to characterize its
      preference for different DNA substrates, its allosteric regulation, and to
      provide a basis for comparison with the bacterial enzymes. We determined that the
      methyl transfer is rate-limiting, and steps up to and including the cysteine
      cytosine covalent intermediate are in rapid equilibrium. Changes in these rapid
      equilibrium steps account for many of the previously described features of Dnmt1
      catalysis and specificity including faster reactions with premethylated DNA
      versus unmethylated DNA, faster reactions with DNA in which guanine is replaced
      with inosine [poly(dC-dG) vs poly(dI-dC)], and 10-100-fold slower catalytic rates
      with Dnmt1 relative to the bacterial enzyme M.HhaI. Dnmt1 interactions with the
      guanine within the CpG recognition site can prevent the premature release of the
      target base and solvent access to the active site that could lead to mutagenic
      deamination. Our results suggest that the beta-elimination step following methyl
      transfer is not mediated by free solvent. Dnmt1 shows a kinetic lag in product
      formation and allosteric inhibition with unmethylated DNA that is not observed
      with premethylated DNA. Thus, we suggest the enzyme undergoes a slow relief from
      allosteric inhibition upon initiation of catalysis on unmethylated DNA. Notably,
      this relief from allosteric inhibition is not caused by self-activation through
      the initial methylation reaction, as the same effect is observed during the
      cytosine C(5) exchange reaction in the absence of AdoMet. We describe limitations
      in the Michaelis-Menten kinetic analysis of Dnmt1 and suggest alternative
      approaches.

PMID- 15996103
TI  - Mediating molecular recognition by methionine oxidation: conformational switching
      by oxidation of methionine in the carboxyl-terminal domain of calmodulin.
AB  - The C-terminus of calmodulin (CaM) functions as a sensor of oxidative stress,
      with oxidation of methionine 144 and 145 inducing a nonproductive association of
      the oxidized CaM with the plasma membrane Ca(2+)-ATPase (PMCA) and other target
      proteins to downregulate cellular metabolism. To better understand the structural
      underpinnings and mechanism of this switch, we have engineered a CaM mutant (CaM
      L7) that permits the site-specific oxidation of M144 and M145, and we have used
      NMR spectroscopy to identify structural changes in CaM and CaM-L7 and changes in
      the interactions between CaM-L7 and the CaM-binding sequence of the PMCA (C28W)
      due to methionine oxidation. In CaM and CaM-L7, methionine oxidation results in
      nominal secondary structural changes, but chemical shift changes and line
      broadening in NMR spectra indicate significant tertiary structural changes. For
      CaM-L7 bound to C28W, main chain and side chain chemical shift perturbations
      indicate that oxidation of M144 and M145 leads to large tertiary structural
      changes in the C-terminal hydrophobic pocket involving residues that comprise the
      interface with C28W. Smaller changes in the N-terminal domain also involving
      residues that interact with C28W are observed, as are changes in the central
      linker region. At the C-terminal helix, (1)H(alpha), (13)C(alpha), and (13)CO
      chemical shift changes indicate decreased helical character, with a complete loss
      of helicity for M144 and M145. Using (13)C-filtered, (13)C-edited NMR
      experiments, dramatic changes in intermolecular contacts between residues in the
      C-terminal domain of CaM-L7 and C28W accompany oxidation of M144 and M145, with
      an essentially complete loss of contacts between C28W and M144 and M145. We
      propose that the inability of CaM to fully activate the PMCA after methionine
      oxidation originates in a reduced helical propensity for M144 and M145, and
      results primarily from a global rearrangement of the tertiary structure of the C
      terminal globular domain that substantially alters the interaction of this domain
      with the PMCA.

PMID- 15996104
TI  - Interactions of gamma T273 and gamma E275 with the beta subunit PSAV segment that
      links the gamma subunit to the catalytic site Walker homology B aspartate are
      important to the function of Escherichia coli F1F0 ATP synthase.
AB  - In Escherichia coli F(1)F(o) ATP synthase, gammaT273 mutants that eliminate the
      ability to form a hydrogen bond to betaV265 were incapable of ATP synthase
      dependent growth and ATPase-dependent proton pumping, had very low rates of
      ATPase activity catalyzed by purified F(1), and had significantly decreased
      sensitivity to inhibition by Mg(2+)-ADP-AlF(n) species, while gammaT273D and
      gammaT273N mutants which maintained or increased the hydrogen bond strength
      maintained or increased catalytic activity. The betaP262G mutation that increases
      the potential flexibility of the rigid sleeve that surrounds the gamma subunit C
      terminus also virtually eliminated ATPase activity and susceptibility to Mg(2+)
      ADP-AlF(n) inhibition. The gammaE275 mutants that retained the ability to form
      the betaV265 hydrogen bond had higher ATPase activity than those that eliminated
      the hydrogen bond. These results provide evidence that the ability to form
      hydrogen bonds between betaV265 and the gamma subunit C-terminus contributes
      significantly to the rate-limiting step of catalysis and to the ability of the
      F(1)F(o) ATP synthase to use a proton gradient to drive ATP synthesis. The loss
      of activity observed with betaP262G may result from increased flexibility
      conferred by glycine that decreases the efficiency of communication between the
      gamma subunit-betaV265 hydrogen bonds and the Walker B aspartate at the catalytic
      site. The partial loss of coupling observed with gammaT273 mutants that eliminate
      the betaV265 hydrogen bond is consistent with participation of this hydrogen bond
      in the escapement mechanism for ATP synthesis in which interactions between the
      gamma subunit and (alphabeta)(3) ring prevent rotation until the empty catalytic
      site binds substrate.

PMID- 15996105
TI  - Affinity and kinetics of sialyl Lewis-X and core-2 based oligosaccharides binding
      to L- and P-selectin.
AB  - Soluble oligosaccharide mimetics of natural selectin ligands act as competitive
      inhibitors of leukocyte adhesion in models of inflammation. We quantified the
      binding of simple oligosaccharides based on sialyl Lewis-X (sLe(X)) and complex
      molecules with the core-2 structure to L- and P-selectin, under both static and
      fluid flow conditions. Isolated human neutrophils were employed to mimic the
      physiological valency of selectins and selectin ligands. Surface plasmon
      resonance studies quantified binding kinetics. We observed the following: (i) The
      functional group at the anomeric position of carbohydrates plays an important
      role during selectin recognition, since sLe(X) and sialyl Lewis-a (sLe(a)) were
      approximately 5-7-fold poorer inhibitors of L-selectin mediated cell adhesion
      compared to their methyl glycosides. (ii) Despite their homology to physiological
      glycans, the putative carbohydrate epitopes of GlyCAM-1 and PSGL-1 bound
      selectins with low affinity comparable to that of sLe(X)-selectin interactions.
      Thus, besides the carbohydrate portion, the protein core of GlyCAM-1 or the
      presentation of carbohydrates in clusters on this glycoprotein may contribute to
      selectin recognition. (iii) A compound
      Galbeta1,4(Fucalpha1,3)GlcNAcbeta1,6(GalNAcbeta1,3)GalNAcalpha-OMe was identified
      which blocked L- and P-selectin binding at 30-100-fold lower doses than sLe(X).
      (iv) Surface plasmon resonance experiments determined that an sLe(X) analogue
      (TBC1269) competitively inhibited, via steric/allosteric mechanisms, the binding
      of two anti-P-selectin function blocking antibodies that recognized different
      epitopes of P-selectin. (v) TBC1269 bound P-selectin via both calcium-dependent
      and -independent mechanisms, with K(D) of approximately 111.4 microM. The
      measured on- and off-rates were high (k(off) > 3 s(-)(1), k(on) > 27,000 M(-)(1)
      s(-)(1)). Similar binding kinetics are expected for sLe(X)-selectin interactions.
      Taken together, our study provides new insight into the kinetics and mechanisms
      of carbohydrate interaction with selectins.

PMID- 15996106
TI  - Stopped-flow Fourier transform infrared spectroscopy allows continuous monitoring
      of azide reduction, carbon monoxide inhibition, and ATP hydrolysis by
      nitrogenase.
AB  - Stopped-flow FTIR spectroscopy was used to monitor continuously the pre-steady-
      and steady-state phases of azide reduction by nitrogenase and the accompanying
      hydrolysis of ATP. This was characterized by a ca. 1.3 s lag phase that is
      explained by the number of Fe protein cycles required to effect the reductions of
      azide to N(2) + NH(3), N(2)H(4) + NH(3), or 3NH(3). Extrapolation of the steady
      state time course for azide reduction to zero time showed that one azide binds
      within 200 ms to each FeMo cofactor. Inhibition of azide reduction by CO was
      established at times <400 ms, which was faster than the appearance of the first
      observable IR band assigned to CO (1904 cm(-)(1) detectable at ca. 1 s with
      maximum amplitude at ca. 7 s). IR bands associated with the rapidly formed (<400
      ms) CO species that inhibits azide reduction were not observed over the range
      1700-2100 cm(-)(1). This suggests either that the CO is initially bridging two or
      more Fe atoms or that a rapid reduction of CO to a formyl state occurs by
      insertion into a metal-hydride bond. The frequencies and time courses for the
      appearance and loss of the CO bands under hi- and lo-CO conditions were
      essentially unaffected by the presence of 20 mM azide, consistent with CO being a
      noncompetitive inhibitor of azide reduction and with azide and CO binding to
      different sites on the FeMo cofactor.

PMID- 15996107
TI  - Self-association energetics of an intact, full-length nuclear receptor: the B
      isoform of human progesterone receptor dimerizes in the micromolar range.
AB  - We are focused on understanding the mechanisms underlying eukaryotic gene
      regulation, using the human progesterone receptor (PR) and its interactions with
      its DNA response elements as a model system. An understanding of PR function is
      complicated by the presence of two transcriptionally distinct isoforms, an 83 kDa
      A-receptor (PR-A) and a 99 kDa B-receptor (PR-B). The two isoforms are identical
      except the B-receptor contains an additional 164 residues at its N-terminus. As a
      first step toward understanding the principles by which the two isoforms assemble
      at complex promoters, we examined the energetics of PR-B self-association using
      sedimentation velocity and sedimentation equilibrium methods. Full-length human
      PR-B was purified to 95% homogeneity from baculovirus-infected insect cells.
      Using a fluorescence hormone binding assay, we determined the purified protein to
      be highly active in its ability to bind ligand. Sedimentation velocity studies of
      hormone-bound PR-B at pH 8.0, 4 degrees C, and 50 mM NaCl demonstrate that it
      undergoes a concentration-dependent change in its sedimentation coefficient,
      existing as a 4.0S species at submicromolar concentrations but forming a 5.7S
      species at higher concentrations. These results strongly suggest that PR-B
      undergoes self-association in the micromolar range. This hypothesis was examined
      rigorously using sedimentation equilibrium. Global analysis of the sedimentation
      equilibrium data demonstrated that PR-B self-association was well described by a
      monomer-dimer model with a dimerization free energy of -7.2 +/- 0.7 kcal/mol. The
      role of NaCl in regulating PR-B dimerization was examined by carrying out
      sedimentation velocity and equilibrium studies under high salt conditions. At 300
      mM NaCl, PR-B is exclusively monomeric in the micromolar range, thus revealing a
      significant ionic contribution to the assembly energetics. Further, the monomer
      sediments as a structurally homogeneous, but highly asymmetric, 4.0S species.
      Limited proteolysis of PR-B demonstrated that the hydrodynamic asymmetry is due
      in part to an extended, nonglobular conformation localized to the N-terminal
      region of PR-B. In contrast, the DNA binding domain (DBD) and hormone binding
      domain (HBD) exist as independent structural units, and the activation function N
      terminal to the DBD (AF-1) shows moderate structure. These results represent the
      first rigorous analysis of the self-assembly energetics of an intact nuclear
      receptor and suggest that PR function is more complex than envisioned by
      traditional models.

PMID- 15996108
TI  - Permeabilization of raft-containing lipid vesicles by delta-lysin: a mechanism
      for cell sensitivity to cytotoxic peptides.
AB  - Delta-lysin is a linear, 26-residue peptide that adopts an alpha-helical,
      amphipathic structure upon binding to membranes. Delta-lysin preferentially binds
      to mammalian cell membranes, the outer leaflets of which are enriched in
      sphingomyelin, cholesterol, and unsaturated phosphatidylcholine. Mixtures
      including these lipids have been shown to exhibit separation between liquid
      disordered (l(d)) and liquid-ordered (l(o)) domains. When rich in sphingomyelin
      and cholesterol, these ordered domains have been called lipid "rafts". We found
      that delta-lysin binds poorly to the l(o) (raft) domains; therefore, in mixed
      phase lipid vesicles, delta-lysin preferentially binds to the l(d) domains. This
      leads to the concentration of delta-lysin in l(d) domains, enhancing peptide
      aggregation and, consequently, the rate of peptide-induced dye efflux from lipid
      vesicles. The efficient lysis of eukaryotic cells by delta-lysin can thus be
      attributed not to specific delta-lysin-cholesterol or delta-lysin-sphingomyelin
      interactions but, rather, to the exclusion of delta-lysin from ordered rafts. The
      degree to which the kinetics of dye efflux are enhanced in mixed-phase vesicles
      over those observed in pure, unsaturated phosphatidylcholine vesicles directly
      reflects the amount of l(d) phase present in mixed-phase systems. This effect of
      lipid domains has broader consequences, beyond the hemolytic efficiency of delta
      lysin. We discuss the hypothesis that bacterial sensitivity to antimicrobial
      peptides may be determined by a similar mechanism.

PMID- 15996109
TI  - Characterization of the membrane domain subunit NuoK (ND4L) of the NADH-quinone
      oxidoreductase from Escherichia coli.
AB  - The ND4L subunit is the smallest mitochondrial DNA-encoded subunit of the proton
      translocating NADH-quinone oxidoreductase (complex I). In an attempt to study the
      functional and structural roles of the NuoK subunit (the Escherichia coli
      homologue of ND4L) of the bacterial NADH-quinone oxidoreductase (NDH-1), we have
      performed a series of site-specific mutations on the nuoK gene of the NDH-1
      operon by using the homologous recombination technique. The amino acid residues
      we targeted included two highly conserved glutamic acids that are presumably
      located in the middle of the membrane and several arginine residues that are
      predicted to be on the cytosolic side. All point mutants examined had fully
      assembled NDH-1 as detected by blue-native gel electrophoresis and
      immunostaining. Mutations of nearly perfectly conserved Glu-36 lead to almost
      null activities of coupled electron transfer with a concomitant loss of
      generation of electrochemical gradient. A significant diminution of the coupled
      activities was also observed with mutations of another highly conserved residue,
      Glu-72. These results may suggest that both membrane-embedded acidic residues are
      important for the coupling mechanism of NDH-1. Furthermore, a severe impairment
      of the coupled activities occurred when two vicinal arginine residues on a
      cytosolic loop were simultaneously mutated. Possible roles of these arginine
      residues and other conserved residues in the NuoK subunit for NDH-1 function were
      discussed.

PMID- 15996110
TI  - De-N-acetyllactotriaosylceramide as a novel cationic glycosphingolipid of bovine
      brain white matter: isolation and characterization.
AB  - A novel cationic lipid was separated from bovine brain white matter by a series
      of chromatographies on carboxymethyl-Sephadex and silica gel in chloroform and
      methanol. Its structure was identified unambiguously as de-N
      acetyllactotriaosylceramide (deNAcLc(3)Cer) by mass spectrometry and (1)H NMR.
      The natural occurrence of this glycolipid in white matter extract was detected by
      immunostaining of thin-layer chromatography with monoclonal antibody 5F5, which
      is directed to deNAcLc(3)Cer and recognizes the terminal beta-glucosaminyl
      (GlcNH(2)) residue, having a free NH(2) group. A de-N-acetylase capable of
      hydrolyzing the N-acetyl group of Lc(3)Cer was detected in bovine brain extract
      using N-[(14)C]acetyl-labeled Lc(3)Cer as a substrate. The biogenesis and
      possible functional significance of deNAcLc(3)Cer are discussed.

PMID- 15996113
TI  - Heterogeneous DNA methylation status of the regulatory element of the mouse Oct4
      gene in adult somatic cell population.
AB  - The transcription factor Oct4 is specifically expressed in the germ line and
      pluripotent stem cells, and is indispensable for normal mouse development. To
      understand the epigenetic control of Oct4 expression, we examined the DNA
      methylation pattern of the Oct4 regulatory element in various types of cells.
      Bisulfite analysis showed that the regulatory element was unmethylated in P19
      embryonal carcinoma cells, which robustly express Oct4. By contrast, the
      regulatory element was distinctly methylated in somatic cells, including cell
      lines, such as NIH3T3 embryonic fibroblast and Hepa1-6 hepatoma, as well as
      tissues from the adult body, such as liver, spleen, and cumulus cells. However,
      we found that the extent of methylation was considerably heterogeneous among the
      alleles in the adult somatic cells. Using a luciferase reporter construct, we
      demonstrated that the extent of methylation directly affects the efficiency of
      gene expression driven by the Oct4 regulatory element in P19 cells. These results
      raise the possibility that the epigenetic status of Oct4 is heterogeneous among a
      population of somatic cells, which may affect the efficiency of Oct4 reactivation
      after somatic cell nuclear transfer.

PMID- 15996112
TI  - Increased gp130 signaling in combination with inhibition of the MEK/ERK pathway
      facilitates embryonic stem cell isolation from normally refractory murine CBA
      blastocysts.
AB  - The standard method for isolation of ES cells from strain 129 mice does not give
      rise to ES lines of CBA origin. We investigated the effect of inhibition of
      MEK/ERK signaling in combination with increased stimulation of gp130 signaling on
      derivation of ES cells from CBA blastocysts. Inhibition of MEKI and MEKII using
      the drug U0126 and stimulation of gp130 signaling by elevating the level of LIF
      present gave rise to ES-like lines in 22.6% of explants. No lines arose when MEK
      was inhibited in the absence of additional LIF stimulation, nor when additional
      LIF stimulation occurred in the absence of MEK inhibition. Typically for ES cell
      lines, CBA-derived cells contributed to chimeric mice and differentiated broadly
      in vitro. Increased levels of gp130 signaling led to similar levels of STAT3
      activation in strain 129 and CBA ES cells. We conclude that CBA ES cells have a
      requirement for additional STAT3 activation.

PMID- 15996114
TI  - Developmental competence of somatic cell nuclear transfer embryos reconstructed
      from oocytes matured in vitro with follicle shells in miniature pig.
AB  - The developmental competence of domestic pig oocytes that were transferred to
      somatic cell nuclei of miniature pig was examined. A co-culture system of oocytes
      with follicle shells was used for the maturation of domestic pig oocytes in
      vitro. Co-cultured oocytes progressed to the metaphase II stage of meiosis more
      quickly and more synchronously than non co-cultured oocytes. Oocytes were
      enucleated and fused with fibroblast cells of Potbelly miniature pig at 48 h of
      maturation. The blastocyst formation rate of nuclear transfer (NT) embryos using
      cocultured oocytes (24%) was significantly higher (p < 0.05) than that of non-co
      cultured oocytes (13%). Cleaved embryos at 48 h after nuclear transfer using co
      cultured oocytes were transferred to the oviducts of 14 Gottingen miniature pigs
      and four Meishan pigs. Estrus of all Gottingens returned at around 20-31 days of
      pregnancy. Two of the four Meishans became pregnant. Three and two cloned piglets
      were born after modest number of embryo transfer (15 and 29 embryos transferred),
      respectively. These results indicated that oocytes co-cultured with follicle
      shells have a high developmental competence after nuclear transfer and result in
      full-term development after embryo transfer.

PMID- 15996115
TI  - Bone morphogenetic proteins produced by cells within embryoid bodies inhibit
      ventral directed differentiation by Sonic Hedgehog.
AB  - Mouse embryoid bodies (EBs) differentiate into dorsal spinal cord neural
      progenitors in response to retinoic acid (RA). Our data demonstrate that the
      addition of Sonic Hedgehog (Shh) directs towards a ventral spinal cord neural
      tube fate, but only at extremely high concentrations. One possible explanation is
      the presence of dorsal directing factors. Bone morphogenetic proteins (BMPs),
      known to direct dorsal spinal cord neural differentiation, were expressed in RA
      treated EBs. Shh more potently directed ventral differentiation when combined
      with the BMP inhibitor Noggin. Further, when BMP7 was added, the ability of Shh
      to direct ventral differentiation was further mitigated.

PMID- 15996116
TI  - Duration of in vitro maturation of recipient oocytes affects blastocyst
      development of cloned porcine embryos.
AB  - This study investigated the effects of different incubation periods for oocyte
      maturation and contact inhibition of donor cells as well as different
      osmolarities for storage of recipient oocytes on fusion rates, cleavage rates,
      and blastocyst yields of porcine somatic nuclear transfer (SCNT) derived embryos.
      In addition, the in vivo developmental potential of cloned embryos derived from
      the most promising SCNT protocol was tested by transfer to recipient gilts.
      Storage of in vitro-matured oocytes for 7.5 h in calcium-free TL-HEPES medium at
      295 or 320 mOsmol prior to activation yielded significantly (p < 0.05) higher
      parthenogenetic blastocyst rates compared to storage in TL-HEPES with an
      osmolarity of 270 mOsmol (24.4 +/- 3.0% and 26.2 +/- 4.3% vs. 18.3 +/- 6.4%,
      respectively, mean +/- SD) and improved the visibility of the polar body.
      Electrical fusion of fibroblasts to enucleated oocytes matured for 38, 40, or 42
      h resulted in similar fusion and cleavage rates (74.8-84.4%). However, nuclear
      transfer with oocytes matured for 40 h in vitro yielded significantly higher (p <
      0.05) development to the blastocyst stage after 7 days of culture (14.7 +/- 1.7%)
      than with oocytes matured for 38 h (9.5 +/- 2.1%) or 42 h (5.1 +/- 2.1%). Contact
      inhibition for 24, 48, or 72 h significantly (p < 0.05) increased the proportion
      of cells at G0/G1 compared with cycling fibroblasts. However, duration of contact
      inhibition of the donor cells for either 24, 48, or 72 h had no effect on
      blastocyst rates of SCNT embryos. Four gilts received an average of 150 SCNT
      embryos (range 138-161) reconstructed with oocytes matured for 40 h; two of these
      became pregnant; one of them went to term and farrowed four piglets on day 115 of
      pregnancy. Microsatellite analysis confirmed that the clones were genetically
      identical with the donor cells. These results show that changes of the in vitro
      maturation protocol may affect in vitro development of reconstructed porcine
      embryos, while duration of the contact inhibition period plays a minor role for
      the success of porcine SCNT. The effects on in vivo development are yet to be
      determined.

PMID- 15996117
TI  - Mouse embryos and chimera cloned from neural cells in the postnatal cerebral
      cortex.
AB  - Cloning of mice has been achieved by transferring nuclei of various types of
      somatic cell nuclei into enucleated oocytes. However, all attempts to produce
      live cloned offspring using the nuclei of neurons from adult cerebral cortex have
      failed. Previously we obtained cloned mice using the nuclei of neural cells
      collected from fetal cerebral cortex. Here, we attempted to generate cloned mice
      using differentiated neurons from the cerebral cortex of postnatal (day 0-4)
      mice. Although we were unable to obtain live cloned pups, many fetuses reached
      day 10.5 days of development. These fetuses showed various abnormalities such as
      spherical omission of the neuroepithelium, collapsed lumen of neural tube, and
      aberrant expressions of marker proteins of neurons. We produced chimeric mice in
      which some hair cells and kidney cells were originated from differentiated
      neurons. In chimeric fetuses, LacZ-positive donor cells were in all three germ
      cell layers. However, chimeras with large contribution of donor-derived cells
      were not obtained. These results indicate that nuclei of differentiated neurons
      have lost their developmental totipotency. In other words, the conventional
      nuclear transfer technique does not allow nuclei of differentiated neurons to
      undergo complete genomic reprogramming required for normal embryonic development.

PMID- 15996118
TI  - Telomere-to-centromere ratio of bovine clones, embryos, gametes, fetal cells, and
      adult cells.
AB  - In 1997, Dolly, the first animal cloned from an adult cell, was born. It was
      announced in 1999 that Dolly might be aging faster than normal because her
      telomeres were shorter than age-matched control sheep. Telomeres, a repeated DNA
      sequence located at the ends of linear chromosomes, allow for base pair loss
      during DNA replication. Telomere shortening acts as a "mitotic clock," leading to
      replicative senescence. By using whole cell lysate and slot-blot analysis, we
      determined the telomere-to-centromere ratio (T/C) for bovine gametes, embryos,
      fetal tissues (brain, heart, lung, kidney, uterus, ovary, and skin), adult donor
      cells, and cloned embryos. Our data indicates a consistency in T/C among the
      various fetal tissues. The T/C of sperm is significantly lower than in oocytes.
      The T/C decreases from the oocyte to the 2-8-cell stage embryo, increases
      dramatically at the morula stage, and decreases at the blastocyst stage. Our data
      shows no significant difference in T/C between cloned embryos and in vitro
      fertilized (IVF) embryos, but there is a significant difference between cloned
      embryos and adult donor cells. In conclusion, the enucleated bovine oocyte has
      the ability to reestablish the telomere length of adult somatic cell donor
      nuclei.

PMID- 15996119
TI  - New assessment of a structural alphabet.
AB  - A statistical analysis of the Protein Databank (PDB) structures had led us to
      define a set of small 3D structural prototypes called Protein Blocks (PBs). This
      structural alphabet includes 16 PBs, each one defined by the (phi, psi) dihedral
      angles of 5 consecutive residues. Here, we analyze the effect of the enlargement
      of the PDB on the PBs' definition. The results highlight the quality of the 3D
      approximation ensured by the PBs. These last could be of great interest in ab
      initio modeling.

PMID- 15996120
TI  - CBCAnalyzer: inferring phylogenies based on compensatory base changes in RNA
      secondary structures.
AB  - The CBCAnalyzer (CBC=compensatory base change) is a custom written software
      toolbox consisting of three parts, CTTransform, CBCDetect, and CBCTree.
      CTTransform reads several ct-file formats, and generates a so called "bracket-dot
      bracket" format that typically is used as input for other tools such as
      RNAforester, RNAmovie or MARNA. The latter one creates a multiple alignment based
      on primary sequences and secondary structures that now can be used as input for
      CBCDetect. CBCDetect counts CBCs in all against all of the aligned sequences.
      This is important in detecting species that are discriminated by their sexual
      incompatibility. The count (distance) matrix obtained by CBCDetect is used as
      input for CBCTree that reconstructs a phylogram by using the algorithm of BIONJ.
      In this note we describe the features of the toolbox as well as application
      examples. The toolbox provides a graphical user interface. It is written in C++
      and freely available at: http://cbcanalyzer.bioapps.biozentrum.uni-wuerzburg.de.

PMID- 15996121
TI  - Normal anatomical imaging of the thorax in three dogs: computed tomography and
      macroscopic cross sections with vascular injection.
AB  - The purpose of this study was to provide a new reference for interpretation of
      the normal anatomy of the canine thorax as imaged using computed tomography (CT).
      Three mature dogs, all mixed breed males, were used for this study. The dogs were
      sedated, anaesthetized and maintained in sternal recumbency. CT study from the
      first to the thirteen thoracic vertebra was performed with a TOSHIBA 600 HQ
      scanner (third generation equipment). Dogs were killed and vascular-injection
      technique was performed: red latex and blue latex filled vascular system.
      Injected dogs were frozen and sectioned with an electric bandsaw, the cuts
      matched as closely as possible to the CT images. The CT images from this study
      are intended as a reference for clinical CT imaging studies of the thoracic
      cavity of the dog and for interpreting lesions of the thorax and associated
      structures.

PMID- 15996122
TI  - Testicular dynamics in Syrian hamsters exposed to both short photoperiod and low
      ambient temperature.
AB  - The object of this study was to determine the details of morphological dynamics
      of spermatogenesis in Syrian hamsters exposed to both short photoperiod and low
      ambient temperature. Eight-week-old male hamsters, kept in a long photoperiod (14
      h L, 10 h D), were transferred to a short photoperiod (6 h L, 18 h D) and kept
      there for 13 weeks to induce testicular regression. Some hamsters were then
      transferred from the room at 23 degrees C to that at 5 degrees C (5 degrees C
      group). Remaining hamsters were continuously kept at 23 degrees C (23 degrees C
      group). Thereafter, the morphology was examined. As a result, it took only 8
      weeks until spermatogenesis recovered in the 23 degrees C group. However, it was
      not until 20 weeks that spermatogenesis was recognized in the 5 degrees C group.
      As the regulation of seasonal testicular activity is characterized by coordinated
      shifts in the relationships among mitosis, meiosis, and apoptosis, the changes in
      the proliferative and apoptotic activities were examined. Although no significant
      difference in proliferative activity of spermatogonia between the 5 degrees C and
      the 23 degrees C groups was confirmed, a notable increase in the rate of
      apoptosis was observed in the 5 degrees C group. Furthermore, this increase was
      more salient during the hibernation period. These findings suggest that both cold
      ambient temperature and hibernation caused the delay of testicular recrudescence
      and this delay arose from the increase of apoptotic activity but not the change
      in proliferative activity in spermatogonia in the 5 degrees C group.

PMID- 15996123
TI  - Immunohistochemical localization of gastrin-releasing peptide, neuronal nitric
      oxide synthase and neurone-specific enolase in the uterus of the North American
      opossum, Didelphis virginiana.
AB  - The present study has demonstrated the immunohistochemical localization of
      gastrin-releasing peptide (GRP), neuronal nitric oxide synthase (nNOS) and
      neurone-specific enolase (NSE) in the uterus of the North American opossum.
      Although the presence of GRP, nNOS and NSE has been reported recently in the
      uterus of eutherian species this is the first description of these peptides in a
      metatherian species. Metatherian mammals are of interest because in these species
      it is the prolonged lactation phase of development that is the period of primary
      reproductive investment rather than intrauterine development as is true of
      eutherian mammals. The opossum, like other marsupial species, has a very
      abbreviated gestation period which in Didelphis lasts only 12.5 days. GRP was
      localized in the cytoplasm of cells forming the surface lining epithelium and the
      glandular epithelium of the opossum endometrium late in pregnancy, at 11.5 days
      of gestation. Likewise, immunoreactivities of nNOS and NSE were found primarily
      within the epithelial cells of the endometrium at 11.5 days of gestation. As
      these peptides and enzymes appear primarily at the time of establishment of the
      yolk sac placenta (between day 10 and day 12.5 gestation), the present results
      strongly suggest that these factors may play a fundamental role in the
      placentation of the opossum.

PMID- 15996124
TI  - A systematic study of brain base arteries in the wild boar (Sus scrofa scrofa).
AB  - This study aimed at describing and systematizing the arteries of the base of the
      brain of the wild boar (Sus scrofa scrofa). Thirty-three heads were used, of
      which 30 were injected with latex, and three with acrylic dental resin through
      the common carotid arteries. The brain carotid artery arose from the rostral
      epidural rete mirabile, and divided into a rostral and a caudal branch. The
      rostral branch gave off the middle cerebral artery and then continued as rostral
      cerebral artery. The latter branched into lateral rhinal, internal ethmoidal and
      medial rhinal arteries. The rostral cerebral artery joined its contralateral
      homologue, becoming the single rostral inter-hemispheric artery. The caudal
      branch emitted the caudal cerebral artery and the tectal arteries, and then fused
      with the branch of the opposite antimere, joining the basilar artery. The rostral
      cerebellar arteries derived from this point. The basilar artery originated from
      the anastomosis between the arteries derived from the caudal epidural rete
      mirabile of each antimere. The basilar artery extended rostrally, giving off as
      main collateral branch the caudal cerebellar artery. The basilar artery presented
      a significant decrease in diameter before joining the caudal branches of the
      brain carotid arteries. The cerebral arterial circle was rostrally and caudally
      closed.

PMID- 15996125
TI  - Immunophenotypical characterization of lymphocyte subpopulations of the uterus of
      non-pregnant and pregnant goats.
AB  - The increased susceptibility during pregnancy to certain pathogens that cause
      abortions may be related to changes in the distribution and phenotype of
      lymphocyte subpopulations in the uterus. Histological, electron microscopic and
      immunocytochemical techniques were used in this study to examine whether such
      variations occur in different stages of the reproductive cycle of goats. The
      study of non-pregnant goats showed that most uterine lymphocytes were T cells and
      displayed both an intraepithelial and stromal distribution. CD8+ T lymphocytes
      were more numerous than CD4+ T lymphocytes. In the endometrial epithelium two
      lymphocyte subpopulations were observed: non-granulated CD2+ CD8+ T lymphocytes
      and granulated CD2+ CD8- T lymphocytes. During gestation, no lymphocytes were
      observed in the placentomal area, while a decreased number of T lymphocyte
      subpopulations were found in the inter-placentomal area. In the inter-caruncular
      epithelium, non-granulated CD2+ CD8+ T lymphocytes disappeared, whereas the
      granulated CD2+ CD8- T lymphocyte subpopulations increased their number and
      changed their morphology.

PMID- 15996126
TI  - Postnatal development of the secretory activity of the goat subcommissural organ.
      A Reissner's fibre and angiotensin II immunohistochemical study.
AB  - Subcommissural organ (SCO) secretory activity of the goat (variations of Capra
      hircus, that live in arid conditions) was examined during the postnatal
      development, using specific antibodies against the Reissner's fibre (AFRU) and
      angiotensin II (AAGII). The SCO was strongly stained with the anti-glycoproteins
      that form the Reissner's fibre and lightly marked with the anti-angiotensin II.
      The AFRU-immunoreactivity (ir) was found in the ependymal and hypendymal cells
      and in the ventricular and peripheral secretory routes of the goat SCO. The
      amount AFRU increases at 6 months and decreases at adult age. In contrast, the
      anti-angiotensin II-ir was mainly found in the adult age, not being practically
      observed at one postnatal month. The AAGII-ir was mainly found in ependymal cells
      in which AFRU-ir was downregulated. In addition, we detected the presence of
      double immunostained for AFRU and AAGII in ependymocytes of the pre-commissural
      and subcommissural parts. In conclusion the present results may suggest a
      functional interrelation between AAGII and the secretory activity of the SCO of
      this kind of goat.

PMID- 15996127
TI  - Histochemical and electron microscopic study on motor neurone degeneration
      following transient spinal cord ischaemia at normothermic conditions in rabbits.
AB  - This study was carried out to investigate the motor neurone degeneration in the
      ventral horn following transient spinal cord ischaemia at normothermic conditions
      in rabbits. Transient spinal cord ischaemia was induced by occlusion of the
      abdominal aorta underneath the left renal artery for 15 min at normothermia (38.7
      degrees C). Sections at the level of L7 were examined using histochemical and
      electron microscopic methods. Cresyl violet-positive motor neurones began to
      reduce in number at 3 h after ischaemia reperfusion, and were not detectable at
      48 h after ischaemia reperfusion. Acid fuchsin-positive motor neurones were
      detected at 1 h after ischaemia reperfusion, significantly increased up to 6 h
      after the ischaemia reperfusion, and eventually disappeared by 48 h after
      ischaemia reperfusion. In electron microscopic findings, the disintegration of
      cytoplasmic membranes, and the disruption of mitochondria and endoplasmic
      reticulum were observed in motor neurones at 30 min after ischaemia reperfusion.
      Motor neurones showed necrotic findings with pyknotic degeneration at 1 h after
      ischaemia reperfusion. The necrotic degeneration became severer time dependently
      after ischaemia reperfusion. At 48 h after ischaemia reperfusion, cellular
      components were not detectable in motor neurones. In conclusion, we suggest that
      the degeneration pattern of motor neurones of the ischaemic spinal cord was
      necrotic after ischaemia reperfusion under normothermic conditions.

PMID- 15996128
TI  - Postnatal modelling of the humeroantebrachial contact areas of radius and ulna in
      dogs.
AB  - Necropsy dogs (n = 234) ranging in age between 2 days and 17 years were examined
      to characterize the cross-sectional shape of the humeroantebrachial contact area
      of the radius and ulna on radioulnar scans of giant, large, mid-sized, small, and
      chondrodystrophic breeds. During growth, the contact areas became more circular
      in shape in all breeds, those in small dogs remained most elliptic. Smallest
      normalized heights (distance between the tip of the anconeal process and the most
      proximal aspect of the cranial margin of the radial head = RUH, distance between
      the tip of the anconeal process and the cranial tip of the medial coronoid
      process = UH) and depths (distance determined in a right angle to RUH = RUD,
      distance determined in a right angle to UH = UD) were noted in large and giant
      breeds with no significant difference between these. In juveniles, a decrease in
      UD was correlated with a decrease in UH in all breeds as was a decrease in RUD
      correlated with a decrease in RUH, whereas in non-arthrotic adults this condition
      could only be proven for mid-sized dogs and small breeds but not for giant, large
      and chondrodystrophic dogs. The average radioulnar and ulnar heights and depths
      (as seen in non-arthrotic adults) were calculated to be obtained in mid-sized
      dogs at least 3-4 weeks earlier than in large dogs. Lipping of the cranial margin
      of the radial head was significantly (P < 0.001) associated with lesion(s) of the
      articular surface (i.e. erosion of the articular cartilage and subchondral bone
      and/or fragmentation of the medial coronoid process) and caused additional change
      in shape of this contact area, which was then even more circular. However, the
      variables evaluated (RUH, RUD, UH, UD) allowed only poor discrimination between
      constitution types and between non-arthrotic and arthrotic joints.

PMID- 15996130
TI  - The canine right caudal and accessory lobe pulmonary veins: revised anatomical
      description, clinical relevance, and embryological implications.
AB  - Necropsy dissections were performed on nine dogs to provide an anatomical
      description of the right caudal and accessory lobe pulmonary veins. In all dogs,
      the pulmonary vein from the right caudal lung lobe initially paralleled the right
      caudal lung lobe bronchus, running cranially, medially, and ventrally. It
      diverged from the bronchus at the level of the pulmonary artery and bronchus of
      the accessory lung lobe. At this point, the pulmonary vein from the right caudal
      lung lobe coursed dorsal to the pulmonary artery and bronchus of the accessory
      lung lobe. Medial to the bronchus of the accessory lung lobe, it received the
      pulmonary vein from the accessory lung lobe on its ventral surface. Within the
      pericardium, this common venous trunk merged with the caudal aspect of the left
      atrium either with or immediately adjacent to the left caudal lobe pulmonary
      vein. These findings were corroborated during surgical dissection to achieve
      isolation of the heart in five dogs as part of an experimental study on
      intravascular gene delivery to the heart. These anatomical findings are relevant
      to clinical and experimental surgery and raise interesting questions about the
      embryological development of pulmonary veins in the dog.

PMID- 15996131
TI  - Observations on the macroscopic digestive anatomy of the Himalayan tahr
      (Hemitragus jemlahicus).
AB  - We measured macroscopic anatomical parameters of the digestive tract of 12 female
      Himalayan tahrs. According to morphological criteria used sensu Hofmann for the
      classification of ruminants into feeding types - in particular the
      reticuloruminal capacity measured as wet content weights, the ruminal pillar
      thickness, the reticular honeycomb structure, the size of the omasum and the size
      of the parotid glands - tahrs can be classified as predominantly grazing
      ruminants. As reported in other ruminant species, the length of the large
      intestine was a more constant parameter over a range of body weights than that of
      the small intestine. The weight of the parotid glands scaled to metabolic body
      weight.

PMID- 15996129
TI  - Cell-specific localization of oestrogen receptor beta (ESR2) mRNA within various
      bovine ovarian cell types using in situ hybridization.
AB  - The localization of oestrogen receptor beta (ESR2) mRNA, in this article
      denominated as (ERbeta) mRNA, was examined using in situ hybridization in the
      ovaries of randomly selected cows, irrespective of the cycle stage of the
      animals. A 602-bp fragment of ERbeta mRNA was cloned, sequenced and digoxigenin
      (DIG)-labelled. Semi-quantitative evaluation showed that the scores for ERbeta
      mRNA were moderate to high in the follicle cells of both primordial and primary
      follicles, but lower in granulosa cells of secondary follicles. In vital tertiary
      follicles, the total ERbeta mRNA expression was low but varied between the
      different animals. In both obliterative and cystic atretic follicles, high to
      moderate ERbeta mRNA scores were noticed in the granulosa cells. The stroma cells
      surrounding primordial and primary follicles and the theca cells of secondary
      follicles showed moderate ERbeta mRNA levels, whereas the ERbeta mRNA score in
      theca interna and theca externa cells of vital tertiary follicles was distinctly
      higher. In the theca cells of atretic follicles the score was even higher. Cells
      of corpora hemorrhagica and corpora lutea had moderate ERbeta mRNA scores, while
      higher scores were seen in cells of corpora albicantia. Cells of the surface
      epithelium had a moderate score for ERbeta mRNA, whereas cells of the tunica
      albuginea and deep stroma showed high ERbeta mRNA scores. The present findings
      have clearly established a cell-specific localization of ERbeta mRNA in several
      cell types in the bovine ovary.

PMID- 15996132
TI  - Mental health research in Australia and New Zealand.

PMID- 15996133
TI  - Queensland Centre for Mental Health Research: the first 17 years.
AB  - OBJECTIVE: To reflect on the establishment and evolution of the Queensland Centre
      for Mental Health Research. METHOD: Narrative historical review. RESULTS: First
      established as an inpatient research unit in December 1987, the focus of the
      Centre evolved in concert with the skills of the staff. After the structure was
      revised in 1996 and 1999, the Centre has evolved into a group with four main
      research streams--epidemiology, developmental neurobiology, genetics and policy
      and economics. Although the group maintains a strong focus on serious mental
      disorders such as schizophrenia, our policy and economic work has a wider
      perspective. The Queensland Centre for Mental Health Research is based in an
      historic mental health service, with laboratories in collaborating universities
      and institutes. Key lessons learnt by the group along the way relate to the
      importance of focusing on a restricted range of research topics in order to build
      a critical mass. CONCLUSIONS: Given a facilitating environment, hospital-based
      research groups can prosper. Over the last 17 years, a cost-efficient, focused
      and productive research group has evolved that has made contributions to
      international research.

PMID- 15996134
TI  - Techniques for the identification of genes involved in psychiatric disorders.
AB  - OBJECTIVE: Most psychiatric disorders are complex genetic traits involving both
      genetic and environmental risk factors. This paper aims to review the gene
      identification strategies being applied by molecular geneticists in their efforts
      to elucidate the genetic and molecular basis of psychiatric disorders. Future
      strategies will also be canvassed. METHOD: The psychiatric genetic literature was
      reviewed to identify current strategies applied to gene identification, with
      examples provided where available. The future strategies and applications that
      will arise from genome projects, including the International Haplotype Mapping
      Project, are also discussed. RESULTS: Many advances in the techniques of gene
      discovery, and the increasing resources available, are rapidly being adopted by
      researchers and applied to the complex problem of identifying susceptibility
      genes for mental illnesses. Perhaps the single most important advance to date is
      the Human Genome Project and all that has stemmed from the vast quantity of
      information that this endeavour has provided. With these technological advances
      and the massive increase of publicly available genetic resources, several genes
      have recently been implicated in the susceptibility to psychiatric illnesses
      including schizophrenia and depression. After many years of fruitless endeavours,
      these recent reports indicate that the labours of researchers in psychiatric
      genetics are beginning to show exciting results. CONCLUSIONS: Identification of
      these susceptibility genes holds great promise, with the unravelling of the
      molecular and biochemical basis of some conditions now being a more realistic and
      tangible goal. The increasing number of genes being identified augers well for
      the future treatment of psychiatric disorders. The genes identified, and the
      pathways of genes and proteins that they implicate, will provide potential novel
      targets for new therapeutic drugs. Psychiatric genetics appears to be poised for
      significant advances in our knowledge and understanding of the molecular genetic
      basis of mental illness.

PMID- 15996135
TI  - Importance of animal models in schizophrenia research.
AB  - OBJECTIVE: This review aims to summarize the importance of animal models for
      research on psychiatric illnesses, particularly schizophrenia. METHOD AND
      RESULTS: Several aspects of animal models are addressed, including animal
      experimentation ethics and theoretical considerations of different aspects of
      validity of animal models. A more specific discussion is included on two of the
      most widely used behavioural models, psychotropic drug-induced locomotor
      hyperactivity and prepulse inhibition, followed by comments on the difficulty of
      modelling negative symptoms of schizophrenia. Furthermore, we emphasize the
      impact of new developments in molecular biology and the generation of genetically
      modified mice, which have generated the concept of behavioural phenotyping.
      CONCLUSIONS: Complex psychiatric illnesses, such as schizophrenia, cannot be
      exactly reproduced in species such as rats and mice. Nevertheless, by providing
      new information on the role of neurotransmitter systems and genes in behavioural
      function, animal 'models' can be an important tool in unravelling mechanisms
      involved in the symptoms and development of such illnesses, alongside approaches
      such as post-mortem studies, cognitive and psychophysiological studies, imaging
      and epidemiology.

PMID- 15996136
TI  - Acute tryptophan depletion. Part I: rationale and methodology.
AB  - OBJECTIVE: Acute tryptophan depletion (ATD) is an experimental technique that has
      been widely used over the last decade to investigate the role of serotonin (5-HT)
      in a variety of disorders. This review, the first of two articles, describes the
      rationale behind this technique and provides detail on how it is applied in
      research settings. METHOD: The authors outline the development of this technique
      with reference to the seminal literature and more recent findings from
      neuroimaging and neuroendocrine studies. This is supplemented by the authors'
      clinical experience of over 5 years of continuous experimental work with this
      paradigm in over 50 subjects. RESULTS: Acute tryptophan depletion is a method
      that significantly reduces central 5-HT in human subjects. Non-serotonergic
      explanations of the effects of ATD have not been confirmed, supporting the
      specificity of this method. CONCLUSIONS: The ATD technique is a valid method of
      manipulating central 5-HT levels. The second article in this series will review
      the application of ATD in depression, anxiety and other psychiatric conditions.

PMID- 15996138
TI  - Imputing missing repeated measures data: how should we proceed?
AB  - OBJECTIVE: This paper compares six missing data methods that can be used for
      carrying out statistical tests on repeated measures data: listwise deletion, last
      value carried forward (LVCF), standardized score imputation, regression and two
      versions of a closest match method. METHOD: The efficacy of each was investigated
      under a variety of sample sizes and with differing levels of missingness.
      Randomly selected samples from a dataset (n = 804) were used to compare the
      methods using t-tests. Efficacy was defined as the closeness of the estimated t
      values to the true t-values from the complete dataset. RESULTS: The results
      suggest a reliable and efficacious basis for imputation method for repeated
      measures data is to substitute a missing datum with a value from another
      individual who has the closest scores on the same variable measured at other
      timepoints, or the average value of four individuals who have the closest scores
      on the same variable at other timepoints. The LVCF and standardized score methods
      performed relatively poorly, which is of concern since these are often
      recommended. Listwise deletion was also an inefficient missing data method.
      CONCLUSIONS: Researchers should consider using closest match missing data
      imputation. Since listwise deletion performed poorly, is widely reported and is
      the default method in many statistical software packages, the findings have broad
      implications.

PMID- 15996137
TI  - Acute tryptophan depletion. Part II: clinical effects and implications.
AB  - OBJECTIVE: This is the second of two articles reviewing the modern dietary
      technique of acute tryptophan depletion (ATD), a method of transiently reducing
      central serotonin levels in both healthy volunteers and clinical populations.
      This article details the clinical studies to date and discusses the implications
      of this research methodology. METHOD: The authors present a review of clinical
      ATD studies collated from a MEDLINE search, unpublished communications and the
      authors' considerable experience with this paradigm. RESULTS: Following from the
      initial use of ATD in subjects with depressive illness, studies of anxiety
      disorders and other psychiatric illnesses have been reported. Sleep, aggressive
      and cognitive effects are also active areas of research and are reviewed here.
      CONCLUSIONS: Acute tryptophan depletion remains a useful psychiatric research
      tool. The findings from the clinical studies reviewed here are summarized and
      implications for future research detailed.

PMID- 15996139
TI  - Imputing cross-sectional missing data: comparison of common techniques.
AB  - OBJECTIVE: Increasing awareness of how missing data affects the analysis of
      clinical and public health interventions has led to increasing numbers of missing
      data procedures. There is little advice regarding which procedures should be
      selected under different circumstances. This paper compares six popular
      procedures: listwise deletion, item mean substitution, person mean substitution
      at two levels, regression imputation and hot deck imputation. METHOD: Using a
      complete dataset, each was examined under a variety of sample sizes and differing
      levels of missing data. The criteria were the true t-values for the entire
      sample. RESULTS: The results suggest important differences. If missing data are
      from a scale where about half the items are present, hot deck imputation or
      person mean substitution are best. Because person mean substitution is
      computationally simpler, similar in its efficiency, advocated by other
      researchers and more likely to be an option on statistical software packages, it
      is the method of choice. If the missing data are from a scale where more than
      half the items are missing, or with single-item measures, then hot deck
      imputation is recommended. The findings also showed that listwise deletion and
      item mean substitution performed poorly. CONCLUSIONS: Person mean and hot deck
      imputation are preferred. Since listwise deletion and item mean substitution
      performed poorly, yet are the most widely reported methods, the findings have
      broad implications.

PMID- 15996140
TI  - Can we track the impact of Australian mental health research?
AB  - OBJECTIVE: Arguments are being made to increase research and development funding
      for mental health research in Australia. Consequently, the methods used to
      measure the results of increased investment require review. This study aimed to
      describe the status of Australian mental health research and to propose potential
      methods for tracking changes in research output. Specifically, we describe the
      research output of nations, Australian states, Australian and New Zealand
      institutions and Australian and New Zealand researchers using citation rates.
      METHOD: Information on research output was sourced from two international
      databases (Institute for scientific information [ISI] Essential Science
      Indicators and ISI Web of Science) and the ISI list of Highly Cited Researchers.
      RESULTS: In an international setting, Australia does not perform as well as other
      comparable countries such as New Zealand or Canada in terms of research output.
      Within Australia, the scientific performance of institutions apparently relates
      to the strength of some individual researchers or consolidated research groups.
      Highly cited papers are evident in the fields of syndrome definition,
      epidemiology and epidemiological methods, cognitive science and prognostic or
      longitudinal studies. CONCLUSIONS: Australian researchers need to consider the
      success of New Zealand and Canadian researchers, particularly given the
      relatively low investment in health and medical research in New Zealand. Although
      citation analyses are fraught with difficulties, they can be effectively
      complemented by other measures of responsiveness to clinical or population needs
      and community expectations and should be conducted regularly and independently to
      monitor the status of Australian mental health research.

PMID- 15996141
TI  - Factors associated with readmission to adolescent psychiatric care.
AB  - OBJECTIVE: The aim of this study is to identify factors associated with
      readmission to adolescent psychiatric inpatient care, in the context of a
      relapsing major mental illness. METHOD: Data were obtained from 71 patients
      admitted to an adolescent psychiatric inpatient unit over a 2-year period.
      Patients who were rehospitalized within 12 months of discharge were compared with
      patients who had only one admission during the study period with respect to
      diagnosis, age of first admission, history of child sexual abuse (CSA) and the
      events precipitating admission. RESULTS: Medication non-adherence and a history
      of CSA were positively and independently associated with relapse readmission,
      while a trend emerged among readmitted patients toward younger age at first
      psychiatric hospitalization. A negative association was found between readmission
      and the experience of personal loss. Readmission was not related to DSM-IV axis I
      or axis II diagnosis, including substance abuse. CONCLUSIONS: The association, in
      an adolescent sample, of medication non-adherence and relapse readmission is
      consistent with findings from numerous adult studies, as is the trend toward
      younger age of first admission. The relationship of a history of CSA to
      readmission has attracted little previous research and the finding of a positive
      association suggests that further investigation of a history of CSA in this
      context is warranted. The implications of these findings and suggestions for
      further research are discussed.

PMID- 15996142
TI  - Low hospital inpatient readmission rate in patients with borderline personality
      disorder: a naturalistic study at Southern Health, Victoria, Australia.
AB  - OBJECTIVE: To study how the standard management protocol and the special
      management contract relate to the clinical profile of patients with borderline
      personality disorder and their hospital admission pattern. METHOD: A
      retrospective review was undertaken using naturalistic data from the Client
      Management Interface over a 2-year period. The standard management protocol
      patient group and the special treatment contract patient group were compared with
      respect to variables which included basic demographic data, number of admissions,
      length of stay and comorbidity. RESULTS: Eighty patients received a diagnosis of
      borderline personality disorder. The majority (81.2%) were managed with the
      standard management protocol and only 41.5% had more than one admission. For
      those who received a special treatment contract (18.8%), 93.3% of them had more
      than one admission. The special treatment contract group had a significantly
      higher total number of admissions (p < 0.001), a higher number of admissions when
      they received (p < 0.001) and did not receive (p = 0.001) a diagnosis of
      borderline personality disorder, a higher number of comorbidities (p = 0.004) but
      not more presentations to the emergency department. CONCLUSIONS: Most patients
      with borderline personality disorder treated with the standard management
      protocol had a low readmission rate. The small group of patients with
      comorbidities managed with a special treatment contract had multiple readmissions
      but not more crisis presentations to the emergency department. Further studies
      are required to elucidate the therapeutic mechanism of the standard management
      protocol and special treatment contract and how that impacts on presentations and
      admissions to a hospital.

PMID- 15996143
TI  - Adverse mental health effects of cannabis use in two indigenous communities in
      Arnhem Land, Northern Territory, Australia: exploratory study.
AB  - OBJECTIVE: We investigated adverse mental health effects and their associations
      with levels of cannabis use among indigenous Australian cannabis users in remote
      communities in the Northern Territory. METHOD: Local indigenous health workers
      and key informants assisted in developing 28 criteria describing mental health
      symptoms. Five symptom clusters were identified using cluster analysis of data
      compiled from interviews with 103 cannabis users. Agreement was assessed (method
      comparison approach, kappa-statistic) with a clinician's classification of the 28
      criteria into five groups labelled: 'anxiety', 'dependency', 'mood', 'vegetative'
      and 'psychosis'. Participants were described as showing 'anxiety', 'dependency'
      etc., if they reported half or more of the symptoms comprising the cluster.
      Associations between participants' self-reported cannabis use and each symptom
      cluster were assessed (logistic regression adjusting for age, sex, other
      substance use). RESULTS: Agreement between two classifications of 28 criteria
      into five groups was 'moderate' (64%, kappa = 0.55, p < 0.001). When five
      clusters were combined into three, 'anxiety-dependency', 'mood-vegetative' and
      'psychosis', agreement rose to 71% (kappa = 0.56, p < 0.001). 'Anxiety
      dependency' was positively associated with number of 'cones' usually smoked per
      week and this remained significant when adjusted for confounders (p = 0.020) and
      tended to remain significant in those who had never sniffed petrol (p = 0.052).
      Users of more than five cones per week were more likely to display 'anxiety
      dependency' symptoms than those who used one cone per week (OR = 15.8, 1.8-141.2,
      p = 0.013). A crude association between the 'mood-vegetative' symptom cluster and
      number of cones usually smoked per week (p = 0.014) also remained statistically
      significant when adjusted for confounders (p = 0.012) but was modified by
      interactions with petrol sniffing (p = 0.116) and alcohol use (p = 0.276). There
      were no associations between cannabis use and 'psychosis'. CONCLUSIONS: Risks for
      'anxiety-dependency' symptoms in cannabis users increased as their level of use
      increased. Other plausible mental health effects of cannabis in this population
      of comparatively new users were probably masked by alcohol use and a history of
      petrol sniffing.

PMID- 15996144
TI  - Samoan and psychiatrists' perspectives on the self: qualitative comparison.
AB  - OBJECTIVES: To compare psychiatrists' perspectives on the meaning of self, in
      general adult public practice psychiatry in the Wellington region of New Zealand,
      with a Samoan view of self and to discuss the implications for the practice of
      psychiatry with Samoan people in New Zealand. METHOD: A focus group of
      psychiatrists was convened for three sessions. A Samoan view of self was
      presented to the participants. Transcripts of the focus groups were analysed
      using inductive content analysis and a process of cultural accountability was
      included in the research design. RESULTS: Individual and secular notions of self
      dominated the psychiatrists' perspectives and contrasted with the primacy of
      relational and spiritual notions of self in Samoan culture. Psychiatrists
      experienced a sense of cultural 'dissonance' on first exposure to the Samoan
      views. The Samoan notion of self was considered to challenge the universalist
      assumptions of Western psychiatric theories as understood by the participants.
      The Samoan relational notion of self had implications for clinical interviewing,
      understanding of phenomenology, formulation and treatment planning with Samoan
      patients and their families. CONCLUSIONS: Dedicated Samoan or Pacific Island
      mental health services would allow culture-specific concepts central to an
      understanding of mental health to be embedded in service delivery. The process
      used in this study and the notion of dialectical tension could be used in the
      cultural education of mental health clinicians. The cultural accountability
      process models an important aspect of such training.

PMID- 15996146
TI  - Anxiety and social worries in children with Asperger syndrome.
AB  - OBJECTIVE: The current study examined anxiety and social worries in a group of
      children with Asperger syndrome (AS). METHOD: Sixty-five children with AS were
      compared with a clinically anxious sample and a normative sample using parent and
      child reports. RESULTS: Comparisons between clinically anxious children and
      children with AS showed similar scores on overall anxiety and on six anxiety
      subscales using child reports. Parent reports revealed higher ratings of overall
      anxiety and described children with AS experiencing more obsessive-compulsive
      symptoms and physical injury fears than clinically anxious children. CONCLUSIONS:
      Children with AS without a diagnosis of anxiety, present with more anxiety
      symptoms than a normal population and with a different profile than a clinically
      anxious population. Study limitations are identified and considerations for
      future research presented.

PMID- 15996145
TI  - Adverse childhood experiences, stressful life events or demographic factors:
      which are important in women's depression? A 2-year follow-up population study.
AB  - OBJECTIVE: The aim of this study was to simultaneously test adverse background
      factors, namely adverse childhood experiences (ACEs), stressful life events and
      prior depressive symptoms, for their ability to predict recovery and non-recovery
      from depression in women among the general population. METHOD: A stratified
      random sample of women (n = 835) from the general population was collected at
      baseline in 1999. Depression (Beck Depression Inventory, BDI-21), ACEs and
      background factors were assessed by postal questionnaire at baseline. Two years
      later, stressful life events during the study phase, social support, use of
      health services and current depression (BDI > or = 13) were similarly assessed.
      RESULTS: Adverse childhood experiences were common among depressed women and
      these past experiences together with the use of health services were associated
      with recovery from depression. Financial difficulties and a poor subjective
      health status associated with non-recovery and current stressful life events
      increased the likelihood of depression on follow-up. Furthermore, the important
      variables explaining depression on follow-up were the quality of social support
      and the existence of prior depressive symptoms at baseline. CONCLUSIONS: Our
      results suggest that women's current depression especially associates with
      stressful life events, insufficient social support, poor subjective health and
      financial difficulties. It seems possible that past adverse experiences
      predispose women to depression, but current stressful events actualize these
      symptoms. In addition, use of health services are associated with recovery in
      women who had ACEs.

PMID- 15996147
TI  - Australian and New Zealand clinical practice guidelines for the treatment of
      anorexia nervosa.

PMID- 15996148
TI  - Lamotrigine add-on to valproate therapy for paediatric bipolar affective
      disorder.

PMID- 15996150
TI  - Early diagnosis can decrease the social and economic burden of social anxiety
      disorder.

PMID- 15996152
TI  - A case of psychogenic polydipsia with underlying stressor.

PMID- 15996156
TI  - Pathological and clinical significance of increased intraepithelial lymphocytes
      (IELs) in small bowel mucosa.
AB  - Intestinal intraepithelial lymphocytes (IELs) belong to a unique T-cell
      population interspersed between epithelial cells of both the small and large
      intestine. It is becoming increasingly recognised that an increased number of
      IELs with a normal villous architecture is within the wide spectrum of
      histological abnormalities observed in coeliac disease. An increased number of
      IELs is the earliest pathological change following gluten challenge and a high
      IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a
      raised IEL count with normal villous architecture is of sufficient clinical
      importance to be reported in routine small bowel biopsies. However, it is evident
      that not all small intestinal biopsy specimens showing increased IELs are
      explained by gluten sensitivity. Increased IELs in small bowel mucosa have also
      been associated with autoimmune disorders, tropical sprue, food protein
      intolerance, Helicobacter pylori-associated gastritis, peptic duodenitis,
      parasitic and viral infections, as well as the development of intestinal
      lymphoma. Histological examination of a biopsy specimen of the small bowel
      remains the diagnostic gold standard for coeliac disease. There will be an ever
      increasing demand for histological confirmation of gluten sensitivity in patients
      in whom the classic microscopic appearance of flattened villi may not have fully
      developed. The more widespread recognition by histopathologists of the pattern of
      injury manifested by increased numbers of IELs in intestinal biopsy specimens
      will certainly help in early diagnosis of coeliac disease, lessen diagnostic
      confusion and influence the modern practice of gastrointestinal tract medicine.
      This review discusses some of the recent developments in clinical pathology
      pertaining to increased IELs in small bowel mucosal biopsies.

PMID- 15996157
TI  - Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine
      response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung
      infection.
AB  - The inflammation in cystic fibrosis (CF) patients with chronic Pseudomonas
      aeruginosa lung infection is dominated by polymorphonuclear neutrophils (PMNs).
      There seems to be a relationship between the PMN-dominated inflammation,
      pronounced antibody production and a Th2-dominated response. Apart from
      mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select
      subsets of dendritic cells, which subsequently induce distinct Th responses.
      Therefore, the present study examines the correlation between the mobilizing
      cytokines in serum and the Th responses. The IFN-gamma and IL-4 production by
      peripheral blood mononuclear cells, and the concentrations of GM-CSF and G-CSF in
      serum as well as lung function, were determined in 37 CF patients with and 6 CF
      patients without chronic P. aeruginosa lung infection. The GM-CSF/G-CSF ratio
      correlated both with the IFN-gamma production and good lung function. In
      addition, an inverse correlation between IL-3 and IFN-gamma was observed. The
      results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed
      Th response in CF, and change to a Th1-dominated response might be achieved with
      GM-CSF treatment.

PMID- 15996158
TI  - The porA pseudogene of Neisseria gonorrhoeae--low level of genetic polymorphism
      and a few, mainly identical, inactivating mutations.
AB  - N. meningitidis is the only Neisseria species known to express two outer membrane
      porins, PorA and PorB. However, a porA pseudogene has been identified in N.
      gonorrhoeae. The present study investigated the prevalence and genetic
      polymorphism of this porA pseudogene in 87 different N. gonorrhoeae strains. The
      porA pseudogene was identified in all isolates. The pseudogene comprised 12
      (5.5%), of which 10 were located in the promoter spacer, and 11 (1.0%)
      polymorphic nucleotide sites in the upstream segment containing the promoter
      region, i.e. the putative -10 and -35 sequences and the promoter spacer in
      between, and the hypothetical PorA coding sequence, respectively. A phylogenetic
      analysis of the upstream segment and the hypothetical coding sequence identified
      36 sequence variants, of which 30 were not previously described. All strains
      comprised at least two identical confirmed inactivating deletions, of which one
      was located in the promoter region and one in the hypothetical PorA coding
      sequence. In conclusion, the porA pseudogene and its few inactivating mutations
      are widespread in the N. gonorrhoeae population and the homology with the N.
      meningitidis porA gene reflects their common evolutionary origin. The highly
      conserved N. gonorrhoeae porA pseudogene may reflect an evolutionary neutral
      molecular clock and may be a suitable genetic target for diagnosis of N.
      gonorrhoeae.

PMID- 15996159
TI  - The comparative importance of E. coli antigen in granulomatous colitis of Boxer
      dogs.
AB  - Granulomatous colitis of Boxer dogs is characterized by mucosal and submucosal
      infiltration by abundant large macrophages and lymphocytes and plasma cells.
      Involved intestine is thickened, corrugated and ulcerated. The macrophages that
      occur in colon, cecum and regional lymph nodes are PAS-positive, lipid-rich,
      contain cholesterol, and some of the time can be seen to hold bacteria. Paraffin
      tissue blocks of formalin-fixed colon and colic lymph nodes from 10 cases were
      cut at 5 microm and immunostained by a streptavidin-biotin immunoperoxidase
      technique, employing primary antibodies against Escherichia coli, E. coli 0157:
      2, Campylobacter, C. jejuni-coli, Yersinia pseudotuberculosis, Salmonella,
      Shigella, Pseudomonas and Lawsonia intracellularis. The macrophages in the lamina
      propria and submucosa, as well as those in aggregates in regional lymph nodes,
      showed immunoreactivity with polyclonal E. coli antibody in all 10 cases. Tissues
      lacking granulomas were negative, as were those reacted with the other eight
      antibodies, with the exception that there was rare focal staining for
      Campylobacter, Lawsonia and Salmonella in a few dogs. We believe these results
      identify the causative agent of this granulomatous disease of Boxer dogs, a
      disease with great histologic and etiologic similarity to granulomatous
      leptomeningitis of Beagle dogs, and malacoplakia and xanthogranulomatous
      cholecystitis of man. Macrophages that are immunopositive for E. coli antigen
      occur in Crohn's disease as well, where their significance is less well
      understood.

PMID- 15996160
TI  - Activation and relocalization of caspase 3 during the apoptotic cascade of human
      mesothelioma cells.
AB  - Apoptosis plays an important role in cancer biology. We investigated the
      expression of caspases 3 and 8 in malignant mesothelioma and malignant
      mesothelioma cell lines and putative changes in their ultrastructural expression
      prior and after exposure to epirubicin. Further studies were conducted to compare
      these changes to the localization and expression of the bcl-2 group of proteins
      bcl-X, bax and mcl-1, and Fas-Fas ligand in the same cells. In the histological
      samples, caspase 3 and 8 immunoreactivity was seen in 27/37 (73%) and 16/37 (43%)
      of the mesotheliomas. The immunostaining was cytoplasmic diffuse, granular, and
      occasionally nuclear. All six mesothelioma cell lines expressed caspases 3 and 8
      by immunoblotting. After exposure to epirubicin the extent of apoptosis was
      increased in all cell lines investigated, being weakest in the most resistant
      M38K cell line. Immunoelectron microscopy revealed immunogold labeling for
      caspases 3 and 8 in the mitochondria with the accumulation of caspase 3 in the
      apoptotic bodies, while the mitochondrial localization of the bcl-2 proteins
      appeared to be very stable. Fas receptor could be detected by flow cytometry,
      whereas the most resistant cell line (M38K) lacked Fas ligand when assessed by RT
      PCR. These results suggest the importance of caspase 3 during the apoptotic
      process of mesothelioma cells and indicate that epirubicin-induced apoptosis is
      independent of the mitochondrial pathway.

PMID- 15996161
TI  - Dedifferentiation of enterochromaffin-like cells in gastric cancer of
      hypergastrinemic cotton rats.
AB  - The role of enterochromaffin-like (ECL) cells in gastric carcinogenesis is not
      fully understood. Spontaneous tumours developing in hypergastrinemic female
      cotton rats have an adenocarcinoma phenotype, but numerous cells in the
      dysplastic mucosa as well as in the carcinomas are positive for neuroendocrine
      markers. In the present study of female cotton rats with 2 and 8 months'
      hypergastrinemia, the oxyntic mucosa of the stomach was examined histologically
      and immunolabelled for histidine decarboxylase (HDC) and pancreastatin, and
      hyperplastic and neoplastic ECL cells were evaluated by electron microscopy.
      These animals developed hyperplasia of the oxyntic mucosa in general and of the
      ECL cells in particular after 2 months and dysplasia and carcinomas after 8
      months. The immunoreactivity of the ECL cells in the oxyntic mucosa was increased
      at 2 months and declined at 8 months. These histological changes were associated
      with progressive loss of secretory vesicles and granules in ECL cells. We suggest
      that ECL cells in hypergastrinemic cotton rats dedifferentiate with time and that
      the gastric carcinomas may develop from ECL cells.

PMID- 15996162
TI  - Adenoid cystic carcinoma of maxillary sinus with metastatic hepatocellular
      carcinoma. Case report.
AB  - A case of collision tumor in the left maxillary sinus composed of adenoid cystic
      carcinoma (ACC) and metastatic hepatocellular carcinoma (HCC) is reported.
      Radiographic examination revealed masses in the liver and bilateral lung
      metastases. Histologically, proliferation of tumor cells with resemblance to HCC
      was observed, in addition to the ACC. For this reason, differential diagnosis
      between a second primary tumor and metastasis was made. The metastatic lesion
      immunohistochemically showed positivity for hepatocyte antigen (OCH1E5) and
      protein induced by vitamin K absence or antagonist II (PIVKA-II), sustaining the
      HCC diagnosis. Primary ACC and metastatic HCC in the maxillary sinus are rare,
      and this may therefore be the first case of maxillary sinus tumor with both these
      elements.

PMID- 15996163
TI  - Carcinosarcoma of the parotid gland: an unusual case with large-cell
      neuroendocrine carcinoma and rhabdomyosarcoma.
AB  - We report a case of carcinosarcoma of the parotid gland in a 72-year-old Japanese
      man. The patient noticed a rapidly enlarging hard mass in the right parotid
      gland. He underwent radical parotidectomy with cervical lymph node dissection.
      The resected tumor measured 3.5 x 4.5 cm and histopathologically showed
      carcinomatous and sarcomatous components. The carcinomatous component consisted
      of large-cell neuroendocrine carcinoma (LCNEC), squamous cell carcinoma and
      adenocarcinoma not otherwise specified, while the sarcomatous component included
      spindle cell sarcoma not otherwise specified, so-called myxosarcoma and
      rhabdomyosarcoma. The LCNEC component was predominant within the whole tumor. The
      diagnoses of LCNEC and rhabdomyosarcoma were also confirmed
      immunohistochemically. With regard to histopathogenesis, based on the lack of
      histopathological evidence and antecedent history of pleomorphic adenoma, we
      considered the present case to be de novo, not expleomorphic adenoma.

PMID- 15996164
TI  - Nail patella syndrome revisited: 50 years after linkage.
AB  - Nail Patella Syndrome (NPS; OMIM #161200) is a pleiotropic condition, with a
      classical clinical tetrad of involvement of the nails, knees, elbows and the
      presence of iliac horns. Kidney disease and glaucoma are now recognised as part
      of the syndrome. Fifty years ago, James Renwick chose NPS to develop methods of
      linkage analysis in humans and revealed the third linkage group identified in man
      -that between NPS and the ABO blood group loci. After a fallow period of some
      forty years, the gene mutated in NPS has been identified (LMX1B) and the
      condition serves as a model for understanding the complex relationships between
      disease loci, modifier genes and the resultant clinical phenotype.

PMID- 15996165
TI  - Polymorphic Alu insertions and their associations with MHC class I alleles and
      haplotypes in the northeastern Thais.
AB  - Polymorphic Alu insertions (POALINs) are known to contribute to the strong
      polymorphic nature of the Major Histocompatibility Complex (MHC). Previous
      population studies on MHC POALINs were limited to only Australian Caucasians and
      Japanese. Here, we report on the individual insertion frequency of the five
      POALINs within the MHC class I region, their HLA-A and -B associations, and the
      three and four locus alpha block POALIN haplotype frequencies in the Northeastern
      (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for
      AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest
      positive associations between the POALINs and HLA class I alleles was between
      AluyMICB and HLA-B*57, AluyHJ and HLA-A*24 and HLA-A*01, and AluyHG and HLA-A*02,
      supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes
      were found more frequently than multiple POALIN haplotypes. However, of the seven
      different POALIN haplotypes within the MHC alpha block, there were only two
      significant differences between the NE Thais, Caucasians and Japanese. This study
      confirms that the MHC POALINs are in linkage disequilibrium with HLA-A and -B
      alleles and that there are significant frequency differences for some of the
      POALINs when compared between NE Thai, Caucasians and Japanese.

PMID- 15996166
TI  - Score statistic to test for genetic correlation for proband-family design.
AB  - In genetic epidemiological studies informative families are often oversampled to
      increase the power of a study. For a proband-family design, where relatives of
      probands are sampled, we derive the score statistic to test for clustering of
      binary and quantitative traits within families due to genetic factors. The
      derived score statistic is robust to ascertainment scheme. We considered
      correlation due to unspecified genetic effects and/or due to sharing alleles
      identical by descent (IBD) at observed marker locations in a candidate region. A
      simulation study was carried out to study the distribution of the statistic under
      the null hypothesis in small data-sets. To illustrate the score statistic, data
      from 33 families with type 2 diabetes mellitus (DM2) were analyzed. In addition
      to the binary outcome DM2 we also analyzed the quantitative outcome, body mass
      index (BMI). For both traits familial aggregation was highly significant. For
      DM2, also including IBD sharing at marker D3S3681 as a cause of correlation gave
      an even more significant result, which suggests the presence of a trait gene
      linked to this marker. We conclude that for the proband-family design the score
      statistic is a powerful and robust tool for detecting clustering of outcomes.

PMID- 15996167
TI  - HLA-DQA1, -DQB1 polymorphism and genetic susceptibility to idiopathic dilated
      cardiomyopathy in Hans of northern China.
AB  - Autoimmune mechanisms are likely to participate in the pathogenesis of at least a
      subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major
      histocompatibility complex (MHC) may serve as markers for the propensity to
      develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II
      genes, especially HLA-DQ genes, which are highly polymorphic, play an important
      role in the activation of immune responses and thus control the predisposition
      to, or protection from, IDC. This study was conducted to investigate the
      association of HLA-DQA1, -DQB1 allele polymorphisms with an autoantibody against
      the myocardial mitochondria ADP/ATP carrier, and to explore susceptibility to
      idiopathic dilated cardiomyopathy (IDC) among the Han ethnic group in northern
      China and the immunological mechanisms and hereditary susceptibility to IDC.
      Polymerase chain reaction sequence-specific primer (PCR-SSP) techniques were used
      to analyze polymorphisms of the second exon of HLA-DQA1 and -DQB1 alleles among
      68 unrelated IDC patients, 4 probands of IDC pedigrees, and 100 healthy controls,
      all of Han nationality and having lived in northern China for a long time.
      Following echocardiography examination the IDC subjects were stratified according
      to ejection fraction (EF) values. Those with EF values higher than 50% were
      placed in subgroup 1, subgroup 2 included the patients with an EF value of 15
      35%, and subgroup 3 consisted of those whose EF values were less than 15%. An
      autoantibody against the myocardial mitochondria ADP/ATP carrier was examined
      using immunoblot analysis. The frequencies of HLA-DQA1*0501 and HLA-DQB1*0303
      were 0.3889 and 0.1806 in the IDC group, significantly higher than those of the
      healthy controls (0.0900 and 0.0364 respectively, both P < 0.05). The OR was 5.20
      (95% CI: 3.60-8.50) and 4.85 (95% CI: 2.56-9.39) respectively. Further analysis
      of the three subgroups showed a higher frequency of HLA-DQA1*0501 among patients
      whose EF was less than 15% than those whose EF values were > or =15%. Conversely,
      the frequencies of HLA-DQA1*0201 and -DQB1*0502, *0504 were significantly lower
      in the IDC group (0.0139, 0.0139 and 0.0417 respectively) than in the control
      group (0.2000, 0.0727 and 0.1091 respectively) (P < 0.05). The frequency of the
      HLA-DQA1*0501 allele was significantly higher in IDC patients whose autoantibody
      is positive in contrast with those whose autoantibody is negative (18.57% vs.
      5.86%, P < 0.05); the relative risk (RR) was 4.32. The other frequencies of HLA
      DQA1 and -DQB1 alleles showed no significant difference in the antibody positive
      and negative groups of IDC patients. The alleles of HLA-DQA1*0501 and HLA
      DQB1*0303 were closely associated with poor EF values in the IDC group, and may
      be involved in susceptibility to the disease. The DQA1*0201 and DQB1*0502, *0504
      alleles may confer protection to IDC among individuals of northern Chinese Han
      nationality. The SER(57) residue in the second exon of DQB1*0502 and *0504 may
      confer resistance to IDC, and defects or substitution of this amino acid residue
      at position 57 of the DQbeta chain may be associated with IDC susceptibility. HLA
      DQ allele polymorphisms may serve as genetic markers for IDC and be involved in
      the regulation of the immune specific response to auto or exterior anti
      myocardium antibodies.

PMID- 15996168
TI  - Worldwide genetic variation at the 3'-UTR region of the LDLR gene: possible
      influence of natural selection.
AB  - The low density lipoprotein receptor gene (LDLR) contains many Alu insertions,
      and is especially Alu-rich at its 3'-untranslated region (3'-UTR). Previous
      studies suggested that the LDLR 3'-UTR could regulate gene expression by the
      stabilization of its mRNA. Given the faster Alu evolutionary rate, and wondering
      about its consequences in a possibly regulatory locus, we have studied
      approximately 800 bp of 222 chromosomes from individuals of African, Asian,
      Caucasian and Amerind ancestry, to better understand the evolution of the
      worldwide genetic diversity at this locus. Twenty-one polymorphic sites,
      distributed in 15 haplotypes, were found. High genetic diversity was observed,
      concentrated in one Alu insertion (Alu U), which also shows a fast evolutionary
      rate. Genetic diversity is similar in all populations except Amerinds, suggesting
      a bottleneck during the peopling of the American continent. Three haplotype
      clusters (A, B, C) are distinguished, cluster A being the most recently formed
      (approximately 500,000 years ago). No clear geographic structure emerges from the
      haplotype network, the global F(st) (0.079) being lower than the average for the
      human genome. When ancestral population growth is taken into account, neutrality
      statistics are higher than expected, possibly suggesting the action of balancing
      selection worldwide.

PMID- 15996169
TI  - MtDNA and Y-chromosome variation in Kurdish groups.
AB  - In order to investigate the origins and relationships of Kurdish-speaking groups,
      mtDNA HV1 sequences, eleven Y chromosome bi-allelic markers, and 9 Y-STR loci
      were analyzed among three Kurdish groups: Zazaki and Kurmanji speakers from
      Turkey, and Kurmanji speakers from Georgia. When compared with published data
      from other Kurdish groups and from European, Caucasian, and West and Central
      Asian groups, Kurdish groups are most similar genetically to other West Asian
      groups, and most distant from Central Asian groups, for both mtDNA and the Y
      chromosome. However, Kurdish groups show a closer relationship with European
      groups than with Caucasian groups based on mtDNA, but the opposite based on the Y
      chromosome, indicating some differences in their maternal and paternal histories.
      The genetic data indicate that the Georgian Kurdish group experienced a
      bottleneck effect during their migration to the Caucasus, and that they have not
      had detectable admixture with their geographic neighbours in Georgia. Our results
      also do not support the hypothesis of the origin of the Zazaki-speaking group
      being in northern Iran; genetically they are more similar to other Kurdish
      groups. Genetic analyses of recent events, such as the origins and migrations of
      Kurdish-speaking groups, can therefore lead to new insights into such migrations.

PMID- 15996170
TI  - Genetic polymorphisms and haplotypes of the human cardiac sodium channel alpha
      subunit gene (SCN5A) in Japanese and their association with arrhythmia.
AB  - Genetic variations in cardiac ion channels have been implicated not only as the
      causes of inherited arrhythmic syndromes, but also as genetic risk factors for
      some acquired arrhythmias. To elucidate the potential roles of genetic
      polymorphisms of the alpha subunit of the voltage-gated sodium channel type V
      (SCN5A) in cardiac rhythm disturbance, the entire SCN5A coding exons and their
      flanking introns were sequenced in 166 Japanese arrhythmic patients and 232
      healthy controls. We detected 69 genetic variations, including 54 novel ones. Out
      of the 12 novel nonsynonymous single nucleotide polymorphisms (SNPs),
      p.Leu1988Arg was found at a frequency of 0.015. The other 11 SNPs were rare
      (0.001), with 6 found in arrhythmic patients and 5 in healthy controls. The
      frequency of a novel intronic SNP, c.703+130G>A, was significantly higher in the
      patients than in the controls, suggesting this SNP is associated with an unknown
      risk factor for arrhythmia. Following linkage disequilibrium analysis, the
      haplotype structure of SCN5A was inferred using high-frequency SNPs. The
      frequency of the haplotype harbouring both p.Leu1988Arg and the common SNP
      p.His558Arg (haplotype GG) was significantly lower in the patients than in the
      controls. This finding suggests that this haplotype (GG) might have been
      positively selected in the controls because of its protective effect against
      arrhythmias. This study provides fundamental information necessary to elucidate
      the effect of genetic variations in SCN5A on channel function and cardiac rhythm
      in Japanese, and probably in the Asian population.

PMID- 15996171
TI  - Family-based association tests for different family structures using pooled DNA.
AB  - DNA pooling is a cost-effective strategy for genomewise association studies to
      identify disease genes. In the context of family-based association studies, Risch
      & Teng (1998) mainly considered families of identical structures to detect
      associations between genetic markers and disease, and suggested possible
      approaches to incorporating different family types without a thorough study of
      their properties. However, families collected in real genetic studies often have
      different structures and, more importantly, the informativeness of each family
      structure depends on the disease model which is generally unknown. So there is a
      need to develop and investigate statistical methods to combine information from
      diverse family types. In this article, we propose a general strategy to
      incorporate different family types by assigning each family an "optimal" weight
      in association tests. In addition, we consider measurement errors in our
      analysis. When we evaluate our approach under different disease models and
      measurement errors, we find that our weighting scheme may lead to a substantial
      reduction in sample size required over the approach suggested by Risch & Teng
      (1998), and measurement errors may have significant impact on the required sample
      size when the error rates are not negligible.

PMID- 15996172
TI  - Y-chromosome lineages from Portugal, Madeira and Acores record elements of
      Sephardim and Berber ancestry.
AB  - A total of 553 Y-chromosomes were analyzed from mainland Portugal and the North
      Atlantic Archipelagos of Acores and Madeira, in order to characterize the genetic
      composition of their male gene pool. A large majority (78-83% of each population)
      of the male lineages could be classified as belonging to three basic Y
      chromosomal haplogroups, R1b, J, and E3b. While R1b, accounting for more than
      half of the lineages in any of the Portuguese sub-populations, is a
      characteristic marker of many different West European populations, haplogroups J
      and E3b consist of lineages that are typical of the circum-Mediterranean region
      or even East Africa. The highly diverse haplogroup E3b in Portuguese likely
      combines sub-clades of distinct origins. The present composition of the Y
      chromosomes in Portugal in this haplogroup likely reflects a pre-Arab component
      shared with North African populations or testifies, at least in part, to the
      influence of Sephardic Jews. In contrast to the marginally low sub-Saharan
      African Y chromosome component in Portuguese, such lineages have been detected at
      a moderately high frequency in our previous survey of mtDNA from the same
      samples, indicating the presence of sex-related gene flow, most likely mediated
      by the Atlantic slave trade.

PMID- 15996173
TI  - A haplotype similarity based transmission/disequilibrium test under founder
      heterogeneity.
AB  - Taking advantage of increasingly available high-density single nucleotide
      polymorphisms (SNP) markers across the genome, various types of
      transmission/disequilibrium tests (TDT) using haplotype information have been
      developed. A practical challenge arising in such studies is the possibility that
      transmitted haplotypes have inherited disease-causing mutations from different
      ancestral chromosomes, or do not bear any disease-causing mutations (founder
      heterogeneity). To reduce the loss of signal strength due to founder
      heterogeneity, we propose an SP-TDT test that combines a sequential peeling
      procedure with the haplotype similarity based TDT method. The proposed SP-TDT
      method is applicable to any size of nuclear family with or without ambiguous
      phase information. Simulation studies suggest that the SP-TDT method has the
      correct type I error rate in stratified populations, and enhanced power compared
      with some existing haplotype similarity based TDT methods. Finally, we apply the
      proposed method to study the association of the leptin gene with obesity from the
      National Heart, Lung, and Blood Institute Family Heart Study.

PMID- 15996174
TI  - G protein beta 3 subunit gene variants and essential hypertension in the northern
      Chinese Han population.
AB  - Recently a novel C825T polymorphism in the G protein beta3 subunit gene was
      identified that showed an association with hypertension in a German population;
      the results of studies in other populations have been inconsistent. To examine
      the contribution of GNB3 polymorphisms to the development of hypertension in the
      northern Chinese Han population, we conducted a case-control study consisting of
      501 hypertensive cases and 503 controls using the G(-350)A, C825T and C1429T
      polymorphisms. Genotypes of samples were determined by PCR and restriction
      digestion. Single locus analysis showed a significant association between G(
      350)A and hypertension (P = 0.01) but no association for C825T or C1429T. The
      three polymorphisms were in tight linkage disequilibrium (D'=-1 for G(-350)A
      C825T, D'= 0.92 for C825T-C1429T) and a total of 7 haplotypes were observed in
      the entire population. Haplotype A-C-C was found to be significantly related to
      hypertension (P = 0.032) and A-C-C carriers had a more than two-fold higher risk
      of hypertension than non-carriers, after adjustment for BMI and glucose. In
      conclusion, our study suggests that G(-350)A is a potential functional
      polymorphism that may be related to hypertension, whereas the C825T and C1429T
      polymorphisms are not associated with hypertension in the northern Chinese Han
      population.

PMID- 15996175
TI  - Multipoint linkage disequilibrium mapping using multilocus allele frequency data.
AB  - This paper describes a likelihood based fine scale linkage disequilibrium mapping
      method for estimating the position of a disease predisposing gene relative to a
      battery of typed marker loci. The method uses multilocus allele frequency data
      from a sample of unrelated diseased individuals and from a sample of unrelated
      control individuals, that is, a case and control type design. This type of data
      could be obtained by typing DNA pools, which is less expensive than typing
      individuals separately. The method described uses a nonparametric model that
      makes it robust to the shape of the genealogy at the disease locus. It can be
      implemented efficiently, making a multipoint analysis of a data set of a thousand
      markers feasible. An example power analysis uses simulations to estimate the
      amount of information that can be extracted from fully resolved haplotype data,
      relative to multilocus allele frequency data. For the assumed parameter values
      and a battery of 10 markers, roughly three times narrower region estimates can be
      derived from haplotype data than from allele frequency data only. Depending on
      how we choose to measure information, allele frequency data at an additional
      approximately 18 or approximately 33 markers is needed to compensate for this
      loss of information.

PMID- 15996182
TI  - Taming the neutrophil: calcium clearance and influx mechanisms as novel targets
      for pharmacological control.
AB  - Neutrophils are relatively insensitive to the anti-inflammatory actions of
      conventional chemotherapeutic agents, including corticosteroids, emphasizing the
      requirement for novel pharmacological strategies to control the potentially
      harmful proinflammatory activities of these cells. In the case of commonly
      occurring inflammatory diseases of the airways, the neutrophil is the primary
      mediator of inflammation in conditions such as chronic obstructive pulmonary
      disease, cystic fibrosis, acute respiratory distress syndrome, bronchiectasis and
      non-eosinophilic bronchial asthma. Recent insights into the mechanisms utilized
      by neutrophils to restore Ca(2+) homeostasis following activation with Ca(2+)
      mobilizing, proinflammatory stimuli have facilitated the identification of novel
      targets for anti-inflammatory chemotherapy in these cells. The most amenable of
      these from a chemotherapeutic perspective, is the cyclic AMP-dependent protein
      kinase-modulated endomembrane Ca(2+)-ATPase which promotes clearance of the
      cation from the cytosol of activated neutrophils. Second generation type 4
      phosphodiesterase inhibitors and adenosine receptor agonists operative at the
      level of subtype A2A adenosine receptors, which are currently undergoing clinical
      and preclinical assessment respectively, hold promise as pharmacologic modulators
      during the restoration of Ca(2+) homeostasis. If this promise is realized, it may
      result in novel chemotherapeutic strategies for the control of hyperacute and
      chronic inflammatory conditions in which neutrophils are primary offenders.
      Alternative, potential future targets include the Na(+), Ca(2+)-exchanger and
      store-operated Ca(2+) channels, which cooperate in the refilling of intracellular
      Ca(2+) stores.

PMID- 15996183
TI  - Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitides.
AB  - There is substantial evidence that T-cells are off balance in antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitides. Genetic risk factors may
      influence shaping of the TCR repertoire and regulatory control of T-cells in
      predisposed individuals. T-cells are found in inflammatory lesions. Vigorous Th1
      type responses are seen in Wegener's granulomatosis and microscopic angiitis,
      whereas a Th2-type response predominates in Churg-Strauss syndrome.
      Oligoclonality and shortened telomers indicate antigen-driven clonal expansion
      and replicative senescence of T-cells in ANCA-associated vasculitides. Potent
      CD28(-) Th1-type cells displaying an effector-memory/late differentiated,
      senescent phenotype are expanded in peripheral blood and are found in
      granulomatous lesions in Wegener's granulomatosis. Differences in proliferative
      peripheral blood T-cell responses to the autoantigens proteinase 3 (PR3)- and
      myeloperoxidase (MPO) have not consistently been detected between patients with
      ANCA-associated vasculitides and healthy controls in vitro. To recognize an
      autoantigen, break tolerance, and maintain autoimmune disease T- and B-cells
      require particular triggers and lymphoid structures. There is preliminary
      evidence of lymphoid-like structures and possible maturation of autoreactive PR3
      ANCA-specific B-cells in granulomatous lesions in Wegener's granulomatosis.
      Alteration of the T-cell response and anomalous autoantigen-presentation in
      lymphoid-structures could facilitate development of autoimmune disease in ANCA
      associated vasculitides.

PMID- 15996184
TI  - One-hit, two-hit . . . is there really any benefit?

PMID- 15996185
TI  - Possible role of autoantibodies against nephrin in an experimental model of
      chronic graft-versus-host disease.
AB  - Nephrin, a product of the NPHS1 gene, is a component of the slit diaphragms that
      are found between glomerular foot processes and is a crucial element for
      glomerular filtration barrier. Recently, nephrin has been focused in a number of
      studies of proteinuria development including various types of acquired glomerular
      diseases including minimal change nephrotic syndrome and membranous nephropathy.
      However, the precise role of nephrin in such acquired glomerular diseases is
      still unknown. To analyse the role of nephrin further, two kinds of anti-nephrin
      antibodies were raised in the rabbits and applied to an experimental mouse model
      of chronic graft-versus-host disease, in which (C57BL/10 x DBA/2) F1 mice
      developed clinically apparent severe proteinuria with significant glomerular
      lesions 7 weeks after parental DBA/2 cell transfer. Antibody-sandwich ELISA
      detected anti-nephrin antibodies during week 2 to week 6, with the peak at week 2
      or week 4. Colocalization of nephrin and IgG on week 4, week 6, and week 8 was
      revealed by confocal microscopic analysis, suggesting that in situ immune complex
      formation with nephrin in glomerular lesion. Taken together, it seems to be
      suggested nephrin and its autoantibody have a certain role in the development of
      glomerular lesion in our model mice.

PMID- 15996186
TI  - Strain-specific differences in perivascular inflammation in lungs in two murine
      models of allergic airway inflammation.
AB  - Histological data show perivascular recruitment of inflammatory cells in lung
      inflammation. However, the process of perivascular inflammation is yet-to-be
      characterized in any systematic manner at cell and molecular levels. Therefore,
      we investigated impact of genetic background on perivascular inflammation in
      acute or chronic airway inflammation in different strains of mice. Further, to
      address molecular mechanisms of perivascular inflammation, we examined
      immunohistochemical expression of vascular adhesion protein-1 (VAP-1) in chronic
      airway inflammation. Histological scoring revealed time and strain specific
      differences in perivascular recruitment of inflammatory cells in chronic and
      acute airway inflammation (P < 0.05). The data show that A/J strain is
      significantly more susceptible for perivascular inflammation followed by BALB/c
      and C57BL/6, while C3H/HeJ strain showed no perivascular accumulation of
      inflammatory cells. Of the two strains examined for perivascular inflammation in
      acute airway inflammation, BALB/c showed more accumulation of inflammatory cells
      compared to C57BL/c. VAP-1 expression occurred in the endothelium of pulmonary
      arteries but not in alveolar septa or airways in the control as well as
      challenged mice. In the inflamed lungs from A/J mice, the VAP-1 staining in
      pulmonary arteries was more intense compared to the other strains. VAP-1 staining
      was generally observed throughout the pulmonary arterial wall in chronic lung
      inflammation. These data show that periarterial inflammation is influenced by the
      genetic background, and may be partially regulated by VAP-1.

PMID- 15996187
TI  - Modulation of the immune response in pristane-induced lupus by expression of
      activation and inhibitory Fc receptors.
AB  - Altered homeostasis in Fcgamma receptor (FcgammaR) expression has been implicated
      in the induction of both immune complex-mediated glomerulonephritis and
      autoantibody production in systemic lupus erythematosus. FcgammaRI and III are
      required for immune complexes to activate inflammatory cells, thereby inciting
      tissue injury. In contrast, FcgammaRIIB functions as a negative regulator of
      immune complex-mediated inflammation and autoantibody production. We investigated
      the role of FcgammaRI/III versus FcgammaRIIB on pristane-induced lupus in mice.
      FcgammaRI/III and FcgammaRIIB-deficient ((-/-)) and control ((+/+)) BALB/c mice
      were injected with either pristane or PBS. Proteinuria and glomerular immune
      deposits were evaluated 9 months after treatment and serial sera were analysed
      for total IgG levels and lupus-specific autoantibodies. The incidence of
      nephritis was higher in pristane-treated FcgammaRIIB(-/-) mice than pristane
      treated FcgammaRI/III(-/-) and (+/+) mice. Hypergammaglobulinaemia and
      spontaneous anti-DNA/chromatin autoantibody production were associated with
      interleukin (IL)-6 over-expression in FcgammaRIIB(-/-) mice and were augmented
      further by pristane treatment when compared to both FcgammaRI/III(-/-) and (+/+)
      mice. Lack of either FcgammaRIIB or FcgammaRI/III had little effect on both anti
      nRNP/Sm and anti-Su production induced by pristane. Our results confirm that
      spontaneous autoimmunity occurs in the absence of FcgammaRIIB. Moreover, the
      lupus-like syndrome induced by pristane in BALB/c mice was regulated by opposing
      activating and inhibitory FcgammaRs. Activating FcgammaRs were required for
      significant proteinuria and unbridled activation in the absence of FcgammaRIIB
      dramatically exacerbated glomerular inflammatory responses. FcgammaRIIB may be a
      key modulator that suppresses cell activation in the inflammatory immune response
      in systemic lupus erythematosus in humans.

PMID- 15996188
TI  - Bacterial lipopolysaccharide both renders resistant mice susceptible to mercury
      induced autoimmunity and exacerbates such autoimmunity in susceptible mice.
AB  - The initiation and severity of systemic autoimmune diseases are influenced by a
      variety of genetic and environmental factors, in particular bacterial infections
      and products. Here, we have employed bacterial lipopolysaccharide (LPS), which
      non-specifically activates the immune system, to explore the involvement of
      innate immunity in mercury-induced autoimmunity in mice. Following treatment of
      mouse strains resistant [DBA/2 (H-2(d))] or susceptible [SJL(H-2(s))] to such
      autoimmunity with mercuric chloride and/or LPS or with physiological saline alone
      (control), their immune/autoimmune responses were monitored. Resistant DBA/2 mice
      were rendered susceptible to mercury-induced autoimmunity by co-administration of
      LPS, exhibiting pronounced increases in the synthesis of IgG1 and IgE, high
      titres of IgG1 deposits in the kidneys and elevated circulating levels of IgG1
      antibodies of different specificities. Furthermore, the percentages of the T
      cells isolated from the spleens of DBA/2 mice exposed to both mercury and LPS
      that produced pro-inflammatory cytokines were markedly increased by in vitro
      stimulation with phorbol myristate acetate (PMA) and ionomycin, which was not the
      case for splenic T cells isolated from mice receiving mercuric chloride, LPS or
      saline alone. In addition, exposure of susceptible SJL mice to mercury in
      combination with LPS aggravated the characteristic features of mercury-induced
      autoimmunity, including increased synthesis of IgG1 and IgE, the production of
      IgG1 anti-nucleolar antibodies (ANolA) and the formation of renal deposits of
      IgG1. In summary, our findings indicate that activation of the innate immune
      system plays a key role in both the induction and severity of chemically induced
      autoimmunity.

PMID- 15996189
TI  - Hypoxia aggravates lipopolysaccharide-induced lung injury.
AB  - The animal model of inflammatory response induced by intratracheal application of
      lipopolysaccharide includes many typical features of acute lung injury or the
      acute respiratory distress syndrome. A number of experimental investigations have
      been performed to characterize the nature of this injury more effectively. In
      inflammatory conditions, hypoxia occurs frequently before and in parallel with
      pulmonary and non-pulmonary pathological events. This current study was designed
      to examine the in vivo effect of hypoxia as a potentially aggravating condition
      in endotoxin-induced lung injury. Lipopolysaccharide, 150 microg, was instilled
      intratracheally into rat lungs, and thereafter animals were exposed to either
      normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later.
      Inflammatory response and tissue damage were evaluated by quantitative analysis
      of inflammatory cells and mediators, surfactant protein and vascular
      permeability. A significantly enhanced neutrophil recruitment was seen in
      lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide
      animals under normoxia. This increased neutrophil accumulation was triggered by
      inflammatory mediators such as tumour necrosis factor-alpha and macrophage
      inflammatory protein-1beta, secreted by alveolar macrophages. Determination of
      vascular permeability and surfactant protein-B showed enhanced concentrations in
      lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals
      previously alveolar macrophage-depleted. This study demonstrates that hypoxia
      aggravates lipopolysaccharide injury and therefore represents a second hit
      injury. The additional hypoxia-induced inflammatory reaction seems to be
      predominantly localized in the respiratory compartment, underlining the
      compartmentalized nature of the inflammatory response.

PMID- 15996190
TI  - Actinobacillus actinomycetemcomitans Y4 capsular polysaccharide induces IL-1beta
      mRNA expression through the JNK pathway in differentiated THP-1 cells.
AB  - Capsular polysaccharide from Actinobacillus actinomycetemcomitans Y4 (Y4 CP)
      induces bone resorption in a mouse organ culture system and osteoclast formation
      in mouse bone marrow cultures, as reported in previous studies. We also found
      that Y4 CP inhibits the release of interleukin (IL)-6 and IL-8 from human
      gingival fibroblast (HGF). Thus Y4 CP induces various responses in localized
      tissue and leads to the secretion of several cytokines. However, the effects of
      Y4 CP on human monocytes/macrophages are still unclear. In this study, THP-1
      cells, which are a human monocytic cell line, were stimulated with Y4 CP, and we
      measured gene expression in inflammatory cytokine and signal transduction
      pathways. IL-1beta and tumour necrosis factor (TNF)-alpha mRNA were induced from
      Y4 CP-treated THP-1 cells. IL-1beta mRNA expression was increased according to
      the dose of Y4 CP, and in a time-dependent manner. IL-1beta mRNA expression
      induced by Y4 CP (100 microg/ml) was approximately 7- to 10-fold greater than
      that in the control by real-time PCR analysis. Furthermore, neither PD98059, a
      specific inhibitor of extracellular signal-regulated kinase nor SB203580, a
      specific inhibitor of p38 kinase prevented the IL-1beta expression induced by Y4
      CP. However, JNK Inhibitor II, a specific inhibitor of c-Jun N-terminal kinase
      (JNK) prevented the IL-1beta mRNA expression induced by Y4 CP in a concentration
      dependent manner. These results indicate that Y4 CP-mediated JNK pathways play an
      important role in the regulation of IL-1beta mRNA. Therefore, Y4 CP-transduced
      signals for IL-1beta induction in the antibacterial action of macrophages may
      provide a therapeutic strategy for periodontitis.

PMID- 15996191
TI  - Regulation of Toll-like receptor (TLR)2 and TLR4 on CD14dimCD16+ monocytes in
      response to sepsis-related antigens.
AB  - Rapid overproduction of proinflammatory cytokines are characteristic of sepsis.
      CD14(dim)CD16(+) monocytes are thought to be major producers of cytokine and have
      been shown to be elevated in septic patients. Toll-like receptors (TLR) are
      pattern recognition receptors important in mediating the innate immune response
      and their activation can lead to production of cytokines. Using whole blood
      culture and flow cytometry we have investigated TLR2 and TLR4 regulation after
      stimulation with sepsis-relevant antigens [lipopolysaccharide (LPS),
      Staphylococcal enterotoxin B (SEB) and peptidoglycan (PGN)]. The percentage of
      CD14(dim)CD16(+) monocyte population expanded at 20 h post-stimulation, after a
      rise in tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 at 2 h. A
      strong positive correlation between the percentage of CD14(dim)CD16(+) monocytes
      and secreted TNF-alpha was demonstrated (r = 0.72). Furthermore, we were able to
      induce expansion of the CD14(dim)CD16(+) population to approximately 35% of all
      monocytes with the addition of recombinant TNF-alpha to the whole blood culture.
      TLR4 was found to be expressed 2.5 times higher on CD14(dim)CD16(+) compared to
      CD14(+) CD16(-) monocytes, while TLR2 expression was similar in both
      subpopulations. The CD14(dim)CD16(+) and CD14(+) CD16(-) monocyte populations
      were different in their response to various antigens. LPS down-regulated TLR4 by
      4.9 times in CD16(+) monocytes compared to only 2.3 times in CD16(-) monocytes at
      2 h. LPS was able to up-regulate TLR2 by 6.2 times after 2 h, with no difference
      between the subpopulations. LPS further up-regulated TLR2 by 18.4 times after 20
      h only in the CD14(+) CD16(-) population. PGN and SEB induced no significant
      changes in TLR2 or TLR4 expression. We hypothesize that following exposure to
      bacterial antigens, subsequent TNF-alpha drives a differentiation of monocytes
      into a CD14(dim)CD16(+) subpopulation.

PMID- 15996192
TI  - Differential expression of chemokine receptors on human IgA+ and IgG+ B cells.
AB  - Organ-specific lymphocyte homing is dependent on the expression of tissue
      specific homing receptors and selected chemokine receptors. During the effector
      phase of an immune response, IgA and IgG antibody-secreting cells (ASC) are
      differently distributed in the body. Still, B cell expression of L-selectin and
      the mucosal homing receptor integrin alpha4beta7 is not related to the isotype
      produced, but only to the site of antigen encounter. In this study, we examined
      if differences in chemokine responsiveness between IgA+ and IgG+ B cells could
      explain their different tissue localization. Circulating CD19+ B cells were
      isolated and their expression of IgA, IgG, and selected chemokine receptors was
      determined by flow cytometry. Few Ig+ cells expressed CCR2, CCR3, or CCR9, and
      there was no difference in the expression of these receptors between IgA+ and
      IgG+ cells. In contrast, CCR4, CCR5, and CXCR3 was expressed on significantly
      more IgG+ than IgA+ cells. The function of chemokine receptors on memory B cells
      and ASC was then tested in the transwell system. IgG+ memory cells migrated to a
      higher extent than IgA+ cells towards the CXCR3 ligand CXCL11/I-TAC, while there
      was only a small migration towards the CCR4 ligand CCL17/TARC and the CCR9 ligand
      CCL25/TECK. ASC migrated poorly to all chemokines tested. In conclusion, this
      study shows that IgG+ and IgA+ memory B cells have a differential expression of
      the Th1 associated chemokine receptor CXCR3, as well as of CCR4 and CCR5. In
      contrast, none of the studied chemokine receptors was preferentially expressed by
      IgA+ cells.

PMID- 15996193
TI  - Salvia miltiorrhiza water-soluble extract, but not its constituent salvianolic
      acid B, abrogates LPS-induced NF-kappaB signalling in intestinal epithelial
      cells.
AB  - Herbal medicine has become an increasing popular therapeutic alternative among
      patients suffering from various inflammatory disorders. The Salvia miltiorrhizae
      water-soluble extract (SME) have been shown to possess antioxidant and anti
      inflammatory properties in vitro. However, the mechanism of action and impact of
      SME on LPS-induced gene expression is still unknown. We report that SME
      significantly abrogated LPS-induced IkappaB phosphorylation/degradation, NF
      kappaB transcriptional activity and ICAM-1 gene expression in rat IEC-18 cells.
      Chromatin immunoprecipitation assay demonstrated that LPS-induced RelA
      recruitment to the ICAM-1 gene promoter was inhibited by SME. Moreover, in vitro
      kinase assay showed that SME directly inhibits LPS induced IkappaB kinase (IKK)
      activity in IEC-18 cells. To investigate the physiological relevance of SME
      inhibitory activity on NF-kappaB signalling, we used small intestinal explants
      and primary intestinal epithelial cells derived from a transgenic mouse
      expressing the enhanced green fluorescent protein (EGFP) under the
      transcriptional control of NF-kappaB cis-elements (cis-NF-kappaB(EGFP)). SME
      significantly blocked LPS-induced EGFP expression and IkappaBalpha
      phosphorylation in intestinal explants and primary IECs, respectively. However,
      salvianolic acid B, an activate component of SME did not inhibit NF-kappaB
      transcriptional activity and IkappaB phosphorylation/degradation in IEC-18 cells.
      These results indicate that SME blocks LPS-induced NF-kappaB signalling pathway
      by targeting the IKK complex in intestinal epithelial cells. Modulation of
      bacterial product-mediated NF-kappaB signalling by natural plant extracts may
      represent an attractive strategy towards the prevention and treatment of
      intestinal inflammation.

PMID- 15996194
TI  - Expression of Toll-like receptor 9 and response to bacterial CpG
      oligodeoxynucleotides in human intestinal epithelium.
AB  - Recognition of repeat CpG motifs, which are common in bacterial, but not in
      mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the
      innate immune system. As the role of TLR9 in the human gut is unknown, we
      determined the spectrum of TLR9 expression in normal and inflamed colon and
      examined how epithelial cells respond to specific TLR9 ligand stimulation. TLR9
      expression was measured in human colonic mucosal biopsies, freshly isolated human
      colonic epithelial cells and HT-29 cells by reverse transcriptase-polymerase
      chain reaction or Western blotting. Colonic epithelial cell cultures were
      stimulated with a synthetic CpG-oligodeoxynucleotide (ODN), exhibiting strong
      immunostimulatory effects in B cells. Interleukin (IL)-8 secretion was determined
      by enzyme-linked immunosorbent assay, nuclear factor-kappaB (NF-kB) activity by
      electrophoretic mobility shift assay and IkB phosphorylation by Western blotting.
      TLR9 mRNA was equally expressed in colonic mucosa from controls (n = 6) and
      patients with ulcerative colitis or Crohn's disease disease (n = 13). HT-29 cells
      expressed TLR9 mRNA and protein and responded to CpG-ODN (P < 0.01), but not to
      non-CpG-ODN stimulation, by secreting IL-8, apparently in the absence of NF-kB
      activation. Primary epithelial cells isolated from normal human colon expressed
      TLR9 mRNA, but were completely unresponsive to CpG-ODN stimulation in vitro. In
      conclusion, differentiated human colonic epithelial cells are unresponsive to
      TLR9 ligand stimulation in vitro despite spontaneous TLR9 gene expression. This
      suggests that the human epithelium is able to avoid inappropriate immune
      responses to luminal bacterial products through modulation of the TLR9 pathway.

PMID- 15996195
TI  - A human oral keratinocyte cell line responds to human heat shock protein 60
      through activation of ERK1/2 MAP kinases and up- regulation of IL-1beta.
AB  - Heat shock proteins (HSP) are released by cells in response to stress signals. It
      is hypothesized that pathogenic bacteria stimulate the cells in the periodontium
      to up-regulate the expression of HSP60, which would stimulate macrophages, and
      possibly other cells, to produce proinflammatory cytokines. We sought to
      determine whether oral keratinocytes responded to recombinant human HSP60 and to
      identify the signalling pathways involved. In addition, whether oral
      keratinocytes are a source of endogenous HSP60 was also investigated. RT-PCR
      revealed that rhHSP60 induced expression of the IL-1beta gene in the Human Oral
      Keratinocyte (HOK-16B) cell line and it was highest at the lowest concentration
      used (0.1 microg/ml). These responses were mediated via activation of p44/42 MAP
      kinases and to a lesser extend the MAP-kinase SAP/JNK. Similar data was obtained
      from analysis of intracellular signalling pathways in HOK-16B cells by rhHSP70
      and LPS (from both E. coli and the oral pathogen Porphyromonas gingivalis).
      However, there was little activation of p38 by rhHSP60. Blocking of the p44/42
      pathway decreased HSP60-induced IL-1beta gene expression and protein secretion.
      In addition, we discovered that self-HSP60 proteins were constitutively secreted
      by HOK-16B cells. Secretion of self-HSP60 was up-regulated in cells treated with
      LPS from P. gingivalis, but down-regulated with LPS from E. coli. To summarize,
      oral keratinocytes respond to exogenous HSP60 by triggering expression of the
      inflammatory cytokine IL-1beta through activation of p44/42 MAP kinase. Oral
      keratinocytes are also a source for self-HSP60 and the secretion of this protein
      may be differentially modified by LPS from different bacterial species. These
      results highlight the importance of oral keratinocytes and HSPs in the
      development of an immune response against bacterial infection.

PMID- 15996196
TI  - Interleukin-15 increases neutrophil adhesion onto human respiratory epithelial
      A549 cells and attracts neutrophils in vivo.
AB  - Interleukin-15 (IL-15) is a neutrophil agonist that plays a role in inflammatory
      disorders, including a variety of pulmonary diseases. Adhesion of neutrophils
      onto pulmonary cells is a major event leading to development of inflammation.
      Recently, elevated levels of IL-15 have been associated with different pulmonary
      diseases. There is no clear evidence that IL-15 modulates cell surface expression
      of adhesion molecules in neutrophils, or that IL-15 is involved in neutrophil
      adhesion onto pulmonary cells. Also, it is not clear if IL-15 induces a
      neutrophilic inflammation in vivo. This study was aimed at elucidation of these
      issues. Neutrophils were treated with IL-15 and cell surface expression of CD11a,
      CD11b, CD11c and CD18 was monitored by flow cytometry. The human respiratory
      epithelial A549 cell line was used as a substrate for the neutrophil adhesion
      assay and cell surface expression of CD50, CD54 and CD106 was monitored in IL-15
      induced A549 cells. The murine air pouch model was used for investigating
      potential neutrophilic inflammation induced by IL-15 in vivo. IL-15 significantly
      increased neutrophil cell surface expression of CD11b and CD18 and up-regulated
      A549 cell surface expression of CD54. Moreover, A549 cells were found to express
      IL-15R components and adhesion of neutrophils onto A549 cells was increased when
      neutrophils or A549 cells were treated with IL-15. Finally, IL-15 induced
      neutrophilic inflammation in vivo and concentrations of IL-6 and CXCL2/MIP-2 were
      increased in IL-15-induced pouches. IL-15 might participate in inflammatory
      pulmonary diseases by attracting neutrophils, modulating cell surface expression
      molecules and increasing neutrophil adhesion onto pulmonary cells.

PMID- 15996197
TI  - Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple
      sclerosis and major depression.
AB  - Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology
      characterized by debilitating fatigue, along with other symptoms, for at least 6
      months. Many studies demonstrate probable involvement of the central and
      autonomic nervous system, as well as a state of generalized immune activation and
      selective immune dysfunction in patients with CFS. The aim of this study was to
      compare the lymphocyte subsets of patients with chronic fatigue syndrome to those
      of patients with major depression and multiple sclerosis as well as those of
      healthy control subjects. No differences were found in total numbers of T cells,
      B cells or natural killer (NK) cells. However, differences were found in T, B and
      NK cell subsets. Patients with major depression had significantly fewer resting T
      (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also
      had significantly more CD20(+)/CD5(+) B cells, a subset associated with the
      production of autoantibodies. Compared to patients with multiple sclerosis,
      patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study
      will be required to determine whether these alterations in lymphocyte subsets are
      directly involved in the pathophysiology of these disorders, or are secondary
      effects of the causal agent(s).

PMID- 15996198
TI  - Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin
      A deficiency.
AB  - A patient with IgA deficiency had a series of positive serum pregnancy tests
      which led to medical and surgical procedures for suspected molar pregnancy. These
      tests were found to be falsely positive due to heterophile antibody. The aim of
      this study was to determine the frequency of false positive betahCG assays in
      sera of IgA deficient patients. Sera from a panel of IgA deficient (IgA < 7
      mg/dl) patients were tested for the presence of betaHCG using three different
      assays, and also for IgG anti-goat and anti-mouse antibodies. Patients were seen
      at Mount Sinai Medical Center and included 54 patients (ages 1-80 years, 32
      females, 22 males) with IgA deficiency. Thirty percent of 54 IgA deficient
      patient sera yielded positive pregnancy tests by one or more of the three betahCG
      assays, however, none of the patients were pregnant. In comparison to sera of
      normal controls, 39% of the patient sera contained significant amounts of anti
      goat antibody and 18% contained significant amounts of anti-mouse antibody. While
      heterophile antibodies are common in IgA deficient serum, false positive assays
      for betahCG in IgA deficient serum have not been previously reported. The
      possibility of false positive test results should be considered prior to invasive
      procedures in IgA deficient patients.

PMID- 15996199
TI  - Oligoclonal T cells are infiltrating the brains of children with AIDS: sequence
      analysis reveals high proportions of identical beta-chain T-cell receptor
      transcripts.
AB  - We have recently described the presence of perivascular CD3+ CD45RO+ T cells
      infiltrating the brains of children with AIDS. To determine whether these
      infiltrates contain oligoclonal populations of T cells, we amplified by PCR beta
      chain T-cell receptor (TCR) transcripts from autopsy brains of four paediatric
      patients with AIDS. The amplified transcripts were cloned and sequenced. Sequence
      analysis of the beta-chain TCR transcripts from all four patients revealed
      multiple identical copies of TCR beta-chain transcripts, suggesting the presence
      of oligoclonal populations of T-cells. These TCR transcripts were novel. The
      presence of oligoclonal populations of T cells in the brains of these four
      paediatric patients with AIDS suggests that these T cells have undergone antigen
      driven proliferation and clonal expansion very likely in situ, in the brains of
      these AIDS patients, in response to viral or self-antigens. Although the
      specificity of the clonally expanded beta-chain TCR transcripts remains to be
      elucidated, none of the beta-chain TCR transcripts identified in this study were
      identical to those specific for HIV-1 antigens that are currently reported in the
      GENBANK/EMBL databases. Certain common CDR3 motifs were observed in brain
      infiltrating T cells within and between certain patients. Large proportions (24
      of 61; 39%) of beta-chain TCR clones from one patient (NP95-73) and 2 of 27 (7%)
      of another patient (NP95-184-O) exhibited substantial CDR3 homology to myelin
      basic protein (MBP)-specific TCR derived from normal donors or TCR expressed in
      the brain of patients with multiple sclerosis (MS) or with viral encephalitis.
      These two patients (NP95-73 and NP95-184-O) also shared HLA class II with the
      normal donors and the MS patients who expressed these homologous TCR. Pathologic
      examination at autopsy of the brains revealed the presence of myelin pallor only
      in patient NP95-73. T-cell clones identified in the brain of patients NP95-73 and
      NP95-184-O may recognize MBP or another CNS self antigen and this recognition may
      be restricted by either DRB1*15 or DQB1*0602 specificities.

PMID- 15996200
TI  - High levels of glucocorticoid receptors in patients with active Crohn's disease
      may predict steroid resistance.
AB  - Up to 20% of Crohn's disease (CD) patients respond poorly to glucocorticoids
      (GC). A product of an alternative splicing of the glucocorticoid receptor (GR)
      premRNA, GRbeta, may play a role as a dominant inhibitor of the glucocorticoid
      response. Increasing evidence suggests that inflammatory cytokines such as
      interleukin (IL)-18 alternate the splicing of the primary transcript between the
      two isoforms GRbeta and GRalpha in hGR gene of CD patients. The aim of this study
      is to assess the expression of GRalpha and GRbeta in patients with CD and to look
      for a possible correlation between these receptors and the response to
      glucocorticoid treatment. Forty-two CD patients and 17 healthy volunteers were
      studied. Quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      was performed using real-time PCR techniques. Serum IL-18 protein levels were
      measured by enzyme-linked immunosorbent assay (ELISA). The amount of hGRalpha
      mRNA in patients in remission was significantly lower than in controls (P <
      0.05). The amount of hGRbeta-mRNA was significantly higher in GC-resistant
      patients in the active stage of disease compared with all other groups (P <
      0.05). Patients in the active stage of the disease had higher levels of IL-18
      than patients in remission and both had higher levels than controls (P < 0.05).
      The amounts of IL-18 were directly correlated with the amount of hGRbeta mRNA in
      GC-resistant patients with an active disease. High levels of hGRbeta might be
      connected to GC resistance. IL-18 might participate in the alternative splicing
      of the hGR preliminary mRNA of CD patients. The results support the theory that
      augmented hGRbeta mRNA expression level in PBMC is connected with GC-resistance
      of CD patients.

PMID- 15996201
TI  - Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions
      of early rheumatoid arthritis in association with production of Mig/CXCL9 by
      synovial fibroblasts.
AB  - Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks
      in the histopathological manifestations of rheumatoid arthritis (RA). This seems
      to be prominent even prior to significant B cell infiltration and/or formation of
      lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell
      accumulation, we examined in situ expression of chemokines and their receptors
      using synovial targeting biopsy specimens, which were obtained under arthroscopy
      from early RA patients. By immunohistochemical staining, plasma cells were found
      to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial
      sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription
      polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues
      obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the
      synovial sublining regions were remarkably high and were likely to be associated
      with interferon (IFN)-gamma expression. Furthermore, cultured synovial
      fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-gamma.
      Our results indicate that in the early stage of RA, plasma cells expressing CXCR3
      may be recruited directly from the circulation into the synovial sublining
      regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.

PMID- 15996202
TI  - Immune effects of therapy with Adalimumab in patients with rheumatoid arthritis.
AB  - The aim of this study was to assess the effect of Adalimumab on different immune
      parameters in patients with RA. Adalimumab was administered (40 mg every other
      week for 26 weeks) to eight patients with RA that were refractory to conventional
      drug therapy. Peripheral blood samples were obtained at days 0, 15 and 180 of
      Adalimumab therapy, and the following immune parameters were assessed: Number,
      phenotype, and function of regulatory T lymphocytes. The induction of apoptosis
      of immune cells and the in vitro and in vivo reactivity towards M. tuberculosis
      were also analysed. All patients responded to Adalimumab (ACR response 50-70),
      and a modest but significant increase in the number and function of regulatory T
      cells was observed at day 15 of anti-TNF-alpha therapy. In addition, an increased
      percent of apoptotic cells was detected in the peripheral blood at day 15 of
      Adalimumab therapy. Unexpectedly, most of these effects were not further observed
      at day 180. However, two patients showed a persistent and marked reduction in the
      reactivity to M. tuberculosis. Although we have found that Adalimumab affects the
      number and function of regulatory T lymphocytes, and the apoptosis of immune
      cells, these effects are transient and its possible causal relationship with the
      therapeutic activity of this biological agent remains to be determined.
      Nevertheless, the down-regulatory effect of Adalimumab on the reactivity to M.
      tuberculosis could be related to an enhanced risk of tuberculosis reactivation.

PMID- 15996203
TI  - How lay people respond to messages about genetics, health, and race.
AB  - There is a growing movement in medical genetics to develop, implement, and
      promote a model of race-based medicine. Although race-based medicine may become a
      widely disseminated standard of care, messages that advocate race-based selection
      for diagnosing, screening and prescribing drugs may exacerbate health
      disparities. These messages are present in clinical genetic counseling sessions,
      mass media, and everyday talk. Messages promoting linkages among genes, race, and
      health and messages emphasizing genetic causation may promote both general racism
      and genetically based racism. This mini-review examines research in three areas:
      studies that address the effects of these messages about genetics on levels of
      genetic determinism and genetic discrimination; studies that address the effects
      of these messages on attitudes about race; and, studies of the impacts of race
      specific genetic messages on recipients. Following an integration of this
      research, this mini-review suggests that the current literature appears
      fragmented because of methodological and measurement issues and offers strategies
      for future research. Finally, the authors offer a path model to help organize
      future research examining the effects of messages about genetics on
      socioculturally based racism, genetically based racism, and unaccounted for
      racism. Research in this area is needed to understand and mitigate the negative
      attitudinal effects of messages that link genes, race, and health and/or
      emphasize genetic causation.

PMID- 15996204
TI  - Genetic regulation of stem cell origins in the mouse embryo.
AB  - 'Stem cell' has practically become a household term, but what is a stem cell and
      where does it come from? Insight into these questions has come from the early
      mouse embryo, or blastocyst, from which three kinds of stem cells have been
      derived: embryonic stem (ES) cells, trophoblast stem (TS) cells, and
      extraembryonic endoderm (XEN) cells. These stem cells appear to derive from three
      distinct tissue lineages within the blastocyst: the epiblast, the trophectoderm,
      and the extraembryonic endoderm. Understanding how these lineages arise during
      development will illuminate efforts to understand the establishment and
      maintenance of the stem cell state and the mechanisms that restrict stem cell
      potency. Genetic analysis has enabled the identification of several genes
      important for lineage decisions in the mouse blastocyst. Among these, Oct4,
      Nanog, Cdx2, and Gata6 encode transcription factors required for the three
      lineages of the blastocyst and for the maintenance their respective stem cell
      types. Interestingly, genetic manipulation of several of these factors can cause
      lineage switching among these stem cells, suggesting that knowledge of key
      lineage-determining genes could help control differentiation of stem cells more
      generally. Pluripotent stem cells have also been isolated from the human
      blastocyst, but the relationship between these cells and stem cells of the mouse
      blastocyst remains to be explored. This review describes the genetic regulation
      of lineage allocation during blastocyst formation and discusses similarities and
      differences between mouse and human ES cells.

PMID- 15996208
TI  - An interaction between the TaqIB polymorphism of cholesterol ester transfer
      protein and smoking is associated with changes in plasma high-density lipoprotein
      cholesterol levels in Turks.
AB  - Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent
      risk factor for atherosclerosis. We investigated the effects of the TaqIB
      polymorphism of cholesterol ester transfer protein (CETP) on CETP activity and
      plasma HDL-C levels in random nondiabetic and self-reported diabetic subjects in
      a population with very low HDL-C levels. The rare B2B2 genotype was associated
      with significantly higher HDL-C levels and lower CETP activity in random subjects
      and with higher HDL-C in diabetic subjects. After stratification of random
      subjects by smoking status, the common B1B1 genotype was associated with lower
      HDL-C levels than the B2B2 genotype. Although smoking was associated with lower
      HDL-C, especially in men, HDL-C levels between smokers and nonsmokers were not
      different in subjects with the B1B2 or B2B2 genotypes. However, smoking (20+
      cigarettes/day) was associated with a marked reduction in HDL-C in the B1B1
      subjects. The B1B1/smoking interaction was not reflected in a difference in CETP
      activity. High triglycerides and elevated body mass index (BMI) lower HDL-C. The
      B2B2 genotype was associated with the highest HDL-C levels, and these levels were
      significantly lower in the hypertriglyceridemic subjects (>or=50th percentile).
      The lowest HDL-C levels were seen in hypertriglyceridemic subjects with the B1B1
      genotype. Although BMI (>or=50th vs<50th percentile) did not affect HDL-C in B2B2
      subjects, a high BMI was associated with markedly lower HDL-C in B1B1 subjects.
      Thus, HDL-C levels in Turks may be modulated by an interaction between the CETP
      TaqIB polymorphism and smoking, as well as an interaction with
      hypertriglyceridemia and BMI.

PMID- 15996209
TI  - Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung
      carcinoma.
AB  - Next to cigarette smoking, genetic factors may contribute to lung cancer risk.
      Pulmonary surfactant components may mediate response to inhaled carcinogenic
      substances and/or play a role in lung function and inflammation. We studied
      associations between surfactant protein (SP) genetic variants and risk in lung
      cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D
      marker alleles. These included 99 patients with small cell lung carcinoma (SCLC,
      n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC,
      n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and
      smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals
      (population control). We found (a) no significant marker associations with SCLC,
      (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when
      compared with population control, (c) the same alleles (1A9, 6A11) associate with
      risk for AC when compared with population (6A11) or clinical control (1A9), and
      (d) the SP-A1-6A4 allele (found in approximately 10% of the population)
      associates with SCC, when compared with population or clinical control. A
      correlation between SP-A variants and lung cancer susceptibility appears to
      exist, indicating that SP-A alleles may be useful markers of lung cancer risk.

PMID- 15996210
TI  - Clinical and molecular characteristics of hereditary non-polyposis colorectal
      cancer families in Southeast Asia.
AB  - Lee S-C, Guo J-Y, Lim R, Soo R, Koay E, Salto-Tellez M, Leong A, Goh B-C.
      Clinical and molecular characteristics of hereditary non-polyposis colorectal
      cancer families in Southeast Asia. Hereditary non-polyposis colorectal cancer
      (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form
      of hereditary colorectal cancer (CRC), but data in Asians are sparse. We
      sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients
      diagnosed below age 40, and/or with multiple primary cancers or familial cancer
      clustering suggestive of HNPCC, and correlated deleterious mutations with
      clinical and tumour features. Forty-six Chinese, Malay and Indian kindreds
      participated. Of the 153 cancers reported in the 46 kindreds, stomach (14%) and
      urogenital cancers (13%) were the most common extracolonic cancers, whereas
      endometrial cancer comprised only 7%. Eleven different MLH1 and 12 MSH2 mutations
      were identified, including nine novel and four recurring mutations in the
      Chinese. One Indian was a compound heterozygote for an MLH1 and MSH2 mutation.
      The MLH1/MSH2 mutation data in the Malays and the Indians represents the first in
      these ethnic groups. Factors strongly associated with deleterious mutations were
      the Amsterdam criteria, family history of stomach or multiple primary cancers,
      and MSI-high tumours, whereas family history of endometrial cancer and young
      cancer age alone correlated poorly. Distinct clinical and molecular
      characteristics were identified among Asian HNPCC kindreds and may have important
      clinical implications.

PMID- 15996211
TI  - Delineation of a supernumerary marker chromosome utilizing a multimodal approach
      of G-banding, fluorescent in situ hybridization, confirmatory P1 artificial
      chromosome fluorescent in situ hybridization, and high-resolution comparative
      genomic hybridization.
AB  - We describe the structure of a supernumerary marker in a child who presented with
      a right atretic ear and multiple congenital anomalies. Using G-banding,
      fluorescent in situ hybridization (FISH), P1 artificial chromosome FISH and high
      resolution comparative genomic hybridization (CGH), the marker was demonstrated
      to be a derivative chromosome resulting from malsegregation of a paternal 8;22
      translocation: 47,XY, +der(22)t(8;22)(q24.1; q11.2). This case is noteworthy
      because the marker, while sharing similarities to der(22) in the Cat Eye syndrome
      (CES), also contains chromosome 8q material. This partial 8q trisomy confounds
      the diagnosis of CES associated with pure trisomy or pure tetrasomy 22q. The
      paternal translocation is noted with prolonged infertility and oligospermia,
      which again highlights the utility and necessity of chromosome analysis in this
      setting.

PMID- 15996212
TI  - A polymorphism in the apolipoprotein A5 gene is associated with weight loss after
      short-term diet.
AB  - Apolipoprotein A5 is a recently discovered apolipoprotein involved primarily in
      triglyceride metabolism. Several single-nucleotide polymorphisms have been
      investigated since the initial report. The -1131T>C polymorphism has been
      associated with higher triglyceride levels and a decreased high-density
      lipoprotein cholesterol as well as with susceptibility to coronary heart disease.
      However, no study has so far emphasized on the association of a dietary
      intervention with apolipoprotein A5 polymorphisms. In a group of 606
      hyperlipaemic and overweight men, we investigated how a short-term fat
      restriction affects lipid traits and body mass index (BMI) in wildtype and
      carriers of the -1131T>C polymorphism. Our result was that the reduction of BMI
      was significantly higher in C allele carriers (p=0.0021). Since the -1131T>C
      polymorphism predisposes to coronary heart disease, a restriction diet is an
      important therapeutic approach in -1131T>C carriers.

PMID- 15996213
TI  - Familial progressive sinoatrial and atrioventricular conduction disease of adult
      onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of
      heart-hand syndrome?
AB  - We identified a family with 10 affected members in four generations suffering
      from adult-onset progressive sinoatrial and atrioventricular conduction disease,
      sudden death due to ventricular tachyarrhythmia, dilated cardiomyopathy, and a
      unique type of brachydactyly with mild hand involvement (short distal, middle,
      proximal phalanges and clinodactyly) and more severe foot involvement (short
      distal, proximal phalanges and metatarsal bones, short or absent middle
      phalanges, terminal symphalangism, duplication of the bases of the second
      metatarsals, extra ossicles, and syndactyly). The phenotype differences from
      other reported genetic abnormalities and linkage exclusion of Holt-Oram syndrome,
      ulnar-mammary syndrome, brachydactyly type B or Robinow syndrome, and cardiac
      conduction disease or Brugada syndrome loci suggest that we report on a new
      hereditary heart-hand syndrome.

PMID- 15996214
TI  - Functional analysis of R75Q mutation in the gene coding for Connexin 26
      identified in a family with nonsyndromic hearing loss.
AB  - Mutations in the gene (GJB2) coding for Connexin 26 (Cx26) are responsible for
      genetic forms of sensorineural hearing loss. This article describes a family
      characterized by congenital profound hearing loss, inherited in an autosomal
      dominant fashion and associated to a R75Q substitution in Cx26. Cell transfection
      and fluorescence imaging, dye transfer experiments and dual patch clamp recording
      showed that the mutant completely prevents the formation of functional channels
      despite assembling into junctional plaques, in communication incompetent HeLa
      cells. The disease is not associated with palmar and plantar keratosis in any of
      the family members, suggesting that R75Q substitution is not sufficient for the
      development of the complete syndromic phenotype. The association of palmar and
      plantar keratosis with profound hearing loss may be dependent on genetic
      background, requiring a functional interaction between the mutated Cx26 and other
      epidermally expressed connexins.

PMID- 15996215
TI  - Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis
      patients of Turkish origin.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative
      childhood-onset disorders characterized by autosomal recessive inheritance,
      epileptic seizures, progressive psychomotor deterioration, visual failure, and
      premature death. At least seven subtypes of childhood-onset NCLs have been
      identified of which the late-infantile-onset forms (LINCLs) are genetically the
      most heterogeneous with four underlying genes identified. A variant form of LINCL
      (vLINCL) present in Turkish patients has been considered a distinct clinical and
      genetic entity (CLN7). However, we recently showed that mutations in the CLN8
      gene account for a subset of Turkish vLINCL. Toward identifying the CLN7 gene we
      here screened the known NCL loci for homozygosity in nine Turkish vLINCL
      families. These loci were excluded in seven families that are likely to represent
      the 'true' Turkish vLINCL. In two families, we identified two novel homozygous
      mutations in the CLN6 gene: an intronic base substitution (c.542+5G>T) affecting
      the splicing of the transcript and a nonsense mutation (c.663C>G) creating a stop
      codon at tyrosine 221. These data indicate that CLN6 mutations, in addition to
      those of CLN8, should be considered a diagnostic alternative in Turkish vLINCL
      patients. The genetic background of the 'true' Turkish vLINCL, CLN7, remains to
      be defined.

PMID- 15996216
TI  - Sitosterolaemia in Switzerland: molecular genetics links the US Amish-Mennonites
      to their European roots.
AB  - Sitosterolaemia is a rare autosomal recessive disease characterized by increased
      intestinal absorption of plant sterols, decreased hepatic excretion into bile and
      elevated concentrations in plasma phytosterols. Homozygous or compound
      heterozygous loss of function mutations in either of the ATP-binding cassette
      (ABC) proteins ABCG5 and ABCG8 explain the increased absorption of plant sterols.
      Here we report a Swiss index patient with sitosterolaemia, who presented with the
      classical symptoms of xanthomas, but also had mitral and aortic valvular heart
      disease. Her management over the last 20 years included a novel therapeutic
      approach of high-dose cholesterol feeding that was semi-effective. Mutational and
      extended haplotype analyses showed that our patient shared this haplotype with
      that of the Amish-Mennonite sitosterolaemia patients, indicating they are related
      ancestrally.

PMID- 15996217
TI  - Vertebral anomalies and cartilaginous tracheal sleeve in three patients with
      Pfeiffer syndrome carrying the S351C FGFR2 mutation.

PMID- 15996218
TI  - Identification of novel TYR and TYRP1 mutations in oculocutaneous albinism.

PMID- 15996219
TI  - A putative new locus for an autosomal recessive cerebellar ataxia syndrome on
      chromosome 22q11.

PMID- 15996220
TI  - Analysis of GJB2 mutation: evidence for a Mediterranean ancestor for the 35delG
      mutation.

PMID- 15996222
TI  - PELD: working well, but only half of the time?

PMID- 15996221
TI  - Noonan-like syndrome mutations in PTPN11 in patients diagnosed with cherubism.

PMID- 15996223
TI  - The potential of paired donation programs: modeling and reality.

PMID- 15996224
TI  - Granulysin: a novel host defense molecule.
AB  - Granulysin is a novel cationic molecule present in the granules of cytotoxic T
      lymphocytes and natural killer cells. Cytotoxic T lymphocytes have long been
      associated with graft destruction in transplant rejection. Recent studies
      implicate granulysin in cell-mediated cytotoxicity, chemoattraction, immune
      activation and as a potential diagnostic biomarker for transplant rejection.

PMID- 15996225
TI  - Toll-like receptor and heme oxygenase-1 signaling in hepatic ischemia/reperfusion
      injury.
AB  - Ischemia/reperfusion injury (IRI) represents the major problem in clinical liver
      transplantation. We have shown that toll-like receptor 4 (TLR4) signaling is
      specifically required in initiating antigen-independent IRI leading to liver
      inflammation, whereas local induction of anti-oxidant heme oxygenase-1 (HO-1) is
      cytoprotective. This study analyzes in vivo interactions between HO-1 and
      sentinel TLR system in the pathophysiology of liver IRI. Using a 90-min lobar
      warm ischemia model, wild type (WT), TLR4 KO/mutant and TLR2 KO mice were first
      assessed for the severity of hepatocellular damage at 6 h postreperfusion. Unlike
      in WT or TLR2-deficient mice, disruption/absence of TLR4 pathway reduced IRI, as
      manifested by liver function (serum alanine aminotransferase levels), histology
      (Suzuki's scores), neutrophil infiltration (myeloperoxidase activity) and
      local/systemic TNF-alpha production (mRNA/protein levels). Moreover, defective
      TLR4 but not TLR2 signaling increased mRNA/protein HO-1 expression. In contrast,
      tin protoporphyrin-mediated HO-1 inhibition restored hepatic damage in otherwise
      IRI-resistant TLR4 mutant/KO mice. CoPP-induced HO-1 overexpression ameliorated
      hepatic damage in IRI-susceptible TLR2 KO mice, comparable with WT controls, and
      concomitantly diminished TLR4 levels. In conclusion, this study highlights the
      importance of cross talk between HO-1 and TLR system in the mechanism of hepatic
      IRI. Hepatic IRI represents a case for innate immunity in which HO-1 modulates
      proinflammatory responses that are triggered via TLR4 signaling, a putative HO-1
      repressor.

PMID- 15996226
TI  - Exogenous thyroid hormone induces liver enlargement, whilst maintaining
      regenerative potential--a study relevant to donor preconditioning.
AB  - We have investigated thyroid hormone- (T3) induced liver cell hyperplasia in rats
      to explore the potential utility of primary mitogens within the clinical context
      of donor conditioning prior to living-related transplantation. A single injection
      of T3 induced a semi-synchronized proliferative response in hepatocytes,
      resulting at 10 days in a peak increase in liver mass, liver/body mass ratio,
      total DNA and total protein. Importantly, the hyperplastic liver induced by T3
      exhibits a commensurate increase in metabolic capacity, as assessed by enhanced
      galactose elimination capacity. Furthermore, when the liver mass had been
      increased by an injection of T3 given 10 days previously and 70% partial
      hepatectomy performed, there was a larger remnant liver mass, liver/body mass
      ratio, total DNA and total protein content 24 h after surgery, compared with
      animals given a control injection. Interestingly, the regenerative response to
      surgery was the same in both groups, indicating that prior T3 conditioning did
      not impair the regenerative response of the liver. Using more stringent
      conditions to test hepatic functional reserve, following 90% hepatectomy, there
      was a greater (57%) survival in animals pre-treated with T3 compared to 14% in
      controls.

PMID- 15996227
TI  - Plasmacytoid dendritic cell precursors induce allogeneic T-cell
      hyporesponsiveness and prolong heart graft survival.
AB  - Dendritic cell (DC) precursors were propagated from C57BL/10 (B10; H2b) mouse
      bone marrow in fms-like tyrosine kinase 3 ligand. Cosignaling molecule (B7-1/B7-2
      and B7-H1) expression and stimulatory capacity of precursor (pre)-plasmacytoid
      (p)DC (CD11c+B220+CD11b-CD19-) and classic myeloid DC (MDC) for allogeneic (C3H;
      H2k) T cells were compared. Unstimulated pre-pDC exhibited very low levels of
      surface MHC class II and classic costimulatory molecules (B7-1/B7-2), whereas a
      minor population expressed B7-H1 at levels higher than on MDC. The pre-pDC were
      ineffective T-cell stimulators and induced nonspecific hyporesponsiveness to
      rechallenge with donor alloantigens in vitro and in vivo. Following stimulation
      with CpG-oligonucleotide (CpG-ODN), B7 molecule expression was upregulated on pre
      pDC, however the ratio between coinhibitory (B7-H1) and costimulatory (B7-1/B7-2)
      signals was much higher (five- to six-fold) on pre-pDC than MDC. Blockade of B7
      H1 expression on pDC increased their T-cell allostimulatory capacity
      significantly. A single preoperative infusion of C3H hosts with pre-pDC prolonged
      B10 heart graft survival significantly but nonspecifically compared with
      untreated mice (median survival times 22 vs. 9 days, respectively). Thus, pre-pDC
      of donor origin have potential to regulate T-cell responses to alloantigens and
      can prolong organ graft survival.

PMID- 15996228
TI  - Improved preservation of the rat heart with celsior solution supplemented with
      cariporide plus glyceryl trinitrate.
AB  - Our aim was to investigate whether the addition of glyceryl trinitrate (GTN), a
      source of nitric oxide, and/or cariporide, a Na/H exchange inhibitor, to a
      commercial preservation solution (Celsior) improved and extended cardiac
      preservation. After baseline indices of cardiac function (aortic flow, coronary
      flow, heart rate, cardiac output) were measured in an isolated working rat heart
      model, hearts were arrested and stored at 2-3 degrees C for 6 or 10 h in Celsior
      solution alone, Celsior supplemented with either 0.1 mg/mL GTN or 10 microM
      cariporide or both. After storage, functional measurements were repeated and
      recovery of each parameter was expressed as a percentage of its pre-storage
      baseline. After 6 h storage, recovery of cardiac function was significantly
      better in hearts stored in GTN- or cariporide-supplemented Celsior solution
      compared with Celsior solution alone. The beneficial effect of GTN was
      significantly abrogated in hearts perfused with glibenclamide prior to storage.
      Significant recovery of cardiac function after 10 h storage was only observed in
      hearts stored in Celsior solution supplemented with both GTN and cariporide.
      Combined supplementation with GTN and cariporide extends the safe period of
      storage of the rat heart and may be a useful approach to enhancing preservation
      of the donor heart.

PMID- 15996229
TI  - Expression of CTL associated transcripts precedes the development of tubulitis in
      T-cell mediated kidney graft rejection.
AB  - The usual phenotype of clinical kidney allograft rejection is infiltration by
      lymphocytes and macrophages and evolution of histologic Banff lesions,
      particularly tubulitis, which indicate parenchymal injury. Using Affymetrix
      microarrays, we evaluated the relationship between the evolution of pathologic
      lesions and the transcriptome. We studied CBA/J into C57Bl/6 mouse kidney
      allografts in which one host kidney is left in place to permit observation of
      lesion development. Histology was dominated by early infiltration by mononuclear
      cells from day 3 and slower evolution of tubulitis after day 7. We defined a set
      of cytotoxic T lymphocyte-associated transcripts (CATs) on the basis of
      expression in purified cytotoxic T lymphocytes (CTL) and in a mixed lymphocyte
      culture, and absence in normal kidney. CATs were detectable by day 3 and highly
      expressed by day 5 in rejecting kidneys, with a median signal 14% of that in CTL,
      compared to 4% in isografts and normal kidneys, and persisted through day 42.
      Lack of mature B cells had little effect on CAT expression, confirming that CATs
      reflect T-cell-mediated rejection. Expression of CATs was established before
      diagnostic lesions and remained remarkably consistent through day 42 despite
      massive alterations in the pathology, and probably reflects T cells recruited to
      the graft.

PMID- 15996230
TI  - Pseudotyping of porcine endogenous retrovirus by xenotropic murine leukemia virus
      in a pig islet xenotransplantation model.
AB  - The potential of porcine endogenous retrovirus (PERV) as a human pathogen,
      particularly as a public health risk, is a major concern for xenotransplantation.
      In vitroPERV transmission to human cells is well established. Evidence from
      human/pig hematopoietic chimeras in immunodeficient mice suggests PERV
      transmission from pig to human cells in vivo. However, recently Yang et al.
      demonstrated in such a model that PERV-C, a nonhuman-tropic class, could be
      transmitted via pseudotyping by xenotropic murine leukemia virus (X-MLV). We
      developed a mouse pig islet xenotransplant model, where pig and human cells are
      located in physically separate compartments, to directly assess PERV transmission
      from a functional pig xenograft. X-MLV efficiently pseudotypes all three classes
      of PERV, including PERV-A and -B that are known to productively infect human cell
      lines and PERV-C that is normally not infectious for human cells. Pseudotyping
      also extends PERV's natural tropism to nonpermissive, nonhuman primate cells. X
      MLV is activated locally by the surgical procedure involved in the tissue
      transplants. Thus, the presence and activation of endogenous X-MLV in
      immunodeficient mice limits the clinical significance of previous reports of in
      vivo PERV transmission from pig tissues to human cells.

PMID- 15996231
TI  - Cell permeable peptide of JNK inhibitor prevents islet apoptosis immediately
      after isolation and improves islet graft function.
AB  - Although application of the Edmonton protocol has markedly improved outcomes for
      pancreatic islet transplantation, the insulin independence rate after islet
      transplantation from one donor pancreas has proven to remain low. During the
      isolation process and subsequent clinical transplantation, islets are subjected
      to severe adverse conditions that impair survival and ultimately contribute to
      graft failure. Pancreas preservation with the two-layer method (TLM) has proven
      to improve transplant results by protecting isolated islets against apoptosis
      through the mitochondrial pathway. However, pancreas storage with TLM cannot
      protect against activation of c-Jun NH2-terminal kinase (JNK) in isolated islets.
      This study investigated whether delivery of a JNK inhibitory peptide (JNKI) via
      the protein transduction system can prevent apoptosis of islet cells immediately
      after isolation. For efficient delivery of the (JNKI into isolated islets, we
      synthesized JNKI as a C-terminal fusion peptide with the 11-arginine protein
      transduction domain (11R-JNKI). 11R efficiently delivered the JNKI into isolated
      islets and 11R-JNKI prevented islet apoptosis immediately after isolation and
      improved islet graft function. These findings suggest that peptide drugs could be
      useful for the prevention of the impairment of islet cells and lead to
      improvement in the outcomes for pancreatic islet transplantation.

PMID- 15996232
TI  - Rosiglitazone protects against cyclosporine-induced pancreatic and renal injury
      in rats.
AB  - Rosiglitazone (RGTZ) has protective effect against various types of injury. This
      study was performed to evaluate the effect of RGTZ on pancreatic and renal injury
      caused by cyclosporine (CsA). CsA (15 mg/kg) and RGTZ (3 mg/kg) were administered
      alone and together to the rats for 28 days. The effect of RGTZ on CsA-induced
      pancreatic injury was evaluated by intraperitoneal glucose tolerance test
      (IPGTT), plasma insulin concentrations and pancreatic beta-cell morphology. The
      effect of RGTZ on CsA-induced renal injury was evaluated by assessing renal
      function and pathology; mediators of inflammation and fibrosis such as
      angiotensin II (AngII), osteopontin (OPN) and transforming growth factor-beta1
      (TGF-beta1) and apoptotic cell death. Four weeks of CsA treatment caused
      diabetes, renal dysfunction, typical pathologic lesions (arteriolopathy,
      interstitial fibrosis and inflammatory cells infiltration) and apoptotic cell
      death. RGTZ treatment decreased blood glucose concentration, increased plasma
      insulin concentration and preserved pancreatic beta islet mass. RGTZ treatment
      improved renal function and histopathology. Pro-inflammatory and pro-fibrotic
      molecules such as AngII, OPN and TGF-beta1, and apoptotic cell death also
      decreased with RGTZ treatment. These data suggest that RGTZ has a protective
      effect against CsA-induced pancreatic and renal injury.

PMID- 15996233
TI  - Regional variation and use of exception letters for cadaveric liver allocation in
      children with chronic liver disease.
AB  - The Pediatric End-Stage Liver Disease (PELD) score was designed to reduce
      subjectivity in liver allocation and to advantage patients with a higher
      probability of waiting list mortality. The aims of this study were to determine
      the impact of PELD implementation for children with chronic liver disease and to
      assess whether PELD met its goal of standardization of liver allocation for
      children. This study used data reported to the United Network for Organ Sharing
      (UNOS) registry for children with chronic liver disease receiving primary
      cadaveric liver transplant between January 2000 and December 2001 (pre-PELD) and
      March 2002 and July 2003 (PELD). PELD reduced the percentage of children
      transplanted while in an intensive care unit and as status 1. A calculated PELD
      score was used for allocation in only 52% of recipients. Thirty percent were
      status 1 at transplant and PELD scores granted by exception were used for
      allocation in 18% of patients. There was regional variation in PELD score at
      allocation and use of exception scores with a significant relationship between
      PELD score and percentage of exception cases. Regional variation suggests that
      PELD has not resulted in standardization of listing practices in pediatric liver
      transplantation.

PMID- 15996234
TI  - Expression of heme oxygenase-1 in human livers before transplantation correlates
      with graft injury and function after transplantation.
AB  - Upregulation of heme oxygenase-1 (HO-1) has been proposed as an adaptive
      mechanism protecting against ischemia/reperfusion (I/R) injury. We investigated
      HO-1 expression in 38 human liver transplants and correlated this with I/R injury
      and graft function. Before transplantation, median HO-1 mRNA levels were 3.4-fold
      higher (range: 0.7-9.3) in donors than in normal controls. Based on the median
      value, livers were divided into two groups: low and high HO-1 expression. These
      groups had similar donor characteristics, donor serum transaminases, cold
      ischemia time, HSP-70 expression and the distribution of HO-1 promoter
      polymorphism. After reperfusion, HO-1 expression increased significantly further
      in the initial low HO-1 expression group, but not in the high HO-1 group.
      Postoperatively, serum transaminases were significantly lower and the bile salt
      secretion was higher in the initial low HO-1 group, compared to the high
      expression group. Immunofluorescence staining identified Kupffer cells as the
      main localization of HO-1. In conclusion, human livers with initial low HO-1
      expression (<3.4 times controls) are able to induce HO-1 further during
      reperfusion and are associated with less injury and better function than initial
      high HO-1 expression (>3.4 times controls). These data suggest that an increase
      in HO-1 during transplantation is more protective than high HO-1 expression
      before transplantation.

PMID- 15996235
TI  - Peritoneovenous shunt as a bridge to liver transplantation.
AB  - Intractable ascites carries great morbidity. The aim of this study was to
      determine the efficacy of peritoneovenous shunt (PVS) in patients listed for
      liver transplantation (LT). Between January 1999 and January 2004, PVS was
      inserted in 36 (30 males and 6 females) cirrhotic patients, 50.3 years of median
      age (range: 30-66), who failed multiple large-volume paracenteses and diuretic
      therapy, when listed for LT. Data were collected until LT or the present time,
      and were compared to an historical cohort (1997-1998) as control. No operative
      death occurred. Four patients died before LT in a median delay of 9 months after
      PVS insertion. PVS provided palliation for intractable ascites in 30 patients
      (83%). Renal function significantly improved (glomerular filtration rate (GFR)
      improved from 0.642 to 0.987 mL/s, p<0.05). Eighteen patients were transplanted
      in a median delay of 6 months (range: 3-12 months) after PVS insertion. When
      compared to the historical cohort of 18 patients, the occurrence of post-LT acute
      renal failure was significantly lower in the PVS group (3/18 vs. 13/18, p<0.05).
      Our results suggest that PVS might be beneficial in patients with refractory
      ascites waiting for LT and could prevent postoperative acute renal failure.

PMID- 15996236
TI  - Significance of hepatitis B virus genotype in liver transplantation for chronic
      hepatitis B.
AB  - Hepatitis B virus (HBV) genotype influences chronic hepatitis B disease profile
      but its relevance in liver transplantation (LTx) is not known. HBV genotype was
      identified by direct sequencing from pre-transplant sera of 119 patients who
      underwent LTx using lamivudine prophylaxis (genotype A,1; B,43; C,74; D,1). The
      baseline characteristics and outcome of 43 genotype B and 74 genotype C patients
      were compared. Genotype B patients had significantly more pre-transplant acute
      flare, worse liver functions and higher model for end-stage liver disease score.
      Fewer genotype B patients had HBeAg (13% vs. 32%; p=0.017), but HBV DNA
      seropositivity (by bDNA assay) was comparable (26% vs. 23%; p=0.727). The 3-year
      graft survival was 83% for genotype B and 89% for genotype C (p=0.2). The rate of
      HBsAg clearance or seroreversion was the same. The cumulative rate of viral
      breakthrough due to lamivudine-resistant mutants at 3 years was 4% for genotype B
      and 21% for genotype C (p=0.017). Liver biopsy after viral breakthrough showed
      recurrent hepatitis B in 7 of 10 genotype C patients, including 2 with fibrosing
      cholestatic hepatitis, and no histologic recurrence in 2 genotype B patients. In
      conclusion, HBV genotypes B and C are associated with different patterns of end
      stage liver diseases that required transplantation, and genotype C may carry a
      greater risk and severity of recurrence due to lamivudine-resistant mutants.

PMID- 15996237
TI  - Employment and health insurance in long-term liver transplant recipients.
AB  - This study was conducted to examine factors affecting health insurance and
      employment status in long-term liver transplant (OLT) recipients. All adult
      primary OLT recipients surviving at least 1 year were surveyed using existing
      questionnaires. Out of 217 eligible recipients, 186 (86%) responded. The median
      age of respondents was 55 years with a median survival after OLT of 3.4 years.
      The majority (98%) of respondents had health insurance coverage. Thirty-four
      (18%) reported having lost and/or having been denied health insurance since OLT,
      and 63 (34%) switched health insurance since OLT. Of the 179 that reported
      employment status, 98 (55%) were employed, including homemakers and students,
      while 39 (22%) were retired and 42 (24%) unemployed. The majority (76%) of those
      unemployed cited poor health as the reason for unemployment, followed by 5 (12%)
      who feared loss of disability or Medicaid benefits. Fourteen reported to have
      been denied or terminated from employment because of their transplant. In the
      regression analysis, employment prior to transplantation (odds ratio (OR)=5.1),
      age less than 57 (OR=5.1), physical function score>52.4 (OR=3.6) and general
      health score>33.3 (OR=7.6) were significantly associated with employment. These
      data may help identify high-risk pre-OLT patients for intervention measures such
      as work rehabilitation.

PMID- 15996238
TI  - Benefit of sustained virological response to combination therapy on graft
      survival of liver transplanted patients with recurrent chronic hepatitis C.
AB  - Recurrent hepatitis C infection is an important cause of progressive fibrosis,
      cirrhosis and graft loss after liver transplantation. Treatment for post
      transplant recurrence results in sustained virological response (SVR) in up to
      30% of cases. The aim of this study was to evaluate the impact of SVR on patients
      and graft survival. Thirty-four patients with an SVR to IFN-ribavirin were
      included. Forty-six nonresponders to the combination formed the control group.
      Follow-up data were recorded every 6 months and included HCV RNA, and the
      occurrence of clinical problems (cirrhosis, decompensation, hepatocellular
      carcinoma, death). A graft biopsy was performed every year. The mean follow-up
      duration was 52 months in responders and 57 months in nonresponders. Two patients
      died in each group of patients. Two patients with SVR developed late virological
      relapse. Fibrosis decreased in 38% of patients with SVR, remained stable in 44%
      and worsened in 18%. In contrast, fibrosis increased in the majority of
      nonresponder patients (74%, p<0.001). At the end of follow-up, no patient without
      cirrhosis at inclusion developed cirrhosis of the graft versus 9 among
      nonresponder patients (p=0.009). No difference in patient survival was observed
      in the two groups. In conclusion, this study shows that HCV eradication has a
      positive impact on graft survival.

PMID- 15996239
TI  - A comparison of populations served by kidney paired donation and list paired
      donation.
AB  - Options for utilizing live donor kidneys from those who are blood type
      incompatible or crossmatch positive with their intended recipients include kidney
      paired donation (KPD), list paired donation (LPD) and desensitization. KPD
      provides live donor kidneys for both recipients but requires a match to another
      incompatible pair, while LPD utilizes the deceased donor pool but is restricted
      by ethical and logistic concerns. We simulated patients and their potential
      donors to determine which recipients could receive a kidney through KPD and LPD.
      With smaller populations (100 pairs or fewer), more kidneys were matched through
      LPD, although the greatest benefit was derived from a combination of LPD and KPD.
      With increasing population sizes, more patients were matched through KPD,
      including almost all patients who would have been eligible for LPD. At population
      sizes predicted to be achieved by a national paired donation system, the role of
      LPD became minimal, with only 3.9% of pairs unmatched through KPD eligible for
      LPD. Considerable overlap was seen between the pairs unmatchable by KPD and those
      ineligible for LPD, namely less-demanded donors and hard-to-match recipients. For
      this population, the best option may be desensitization.

PMID- 15996240
TI  - High pre-transplant soluble CD30 levels are predictive of the grade of rejection.
AB  - In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients
      are associated with increased rejection and graft loss. We investigated whether
      pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre
      transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16
      patients with vascular rejection (VR) and an age-matched control group of 41
      patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies
      were immunostained for C4d. The median sCD30 level was significantly elevated in
      the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103
      U/mL, range: 36-309, p<0.001) and NR (179 U/mL, range: 70-343, p<0.03). Moreover,
      patients with TIR had significantly lower sCD30 levels compared to NR. Based on
      C4d staining, a TH2 driven process, the median sCD30 levels were significantly
      raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, p<0.05).
      sCD30 levels measured at time of transplantation correlate with the grade of
      rejection. High pre-transplant levels are associated with antibody-mediated
      rejection which carries a poorer prognosis. sCD30 could be another tool to assess
      immunological risk prior to transplantation and enable a patient centered
      approach to immunosuppression.

PMID- 15996241
TI  - A prospective longitudinal study of BK virus infection in 104 renal transplant
      recipients.
AB  - BK virus (BKV) infection during the first year after renal transplantation was
      studied prospectively in 104 unselected consecutive patients. Viral DNA in urine
      (DNAuria) and plasma (DNAemia) samples was detected and quantified by real-time
      PCR. The noncoding control region (NCCR) of BKV isolates was sequenced. DNAuria
      and DNAemia occurred in 57% and 29% of patients, respectively. Three groups were
      defined, uninfected patients (group 1, n=45), patients with DNAuria (group 2,
      n=29) and patients with positive DNAemia (group 3, n=30). Active infection
      started within the first 3 months in 80% of patients. Cold ischemia duration over
      24 h and the administration of tacrolimus were identified as significant risks
      factors for DNAuria, whereas it remains more frequently negative in patients
      receiving cyclosporine A. The risk for positive DNAemia was higher in patients
      with DNAuria (notably for viral load (VL)>4 log/mL) or treated with tacrolimus.
      No relationship was found with genetic variability in the NCCR sequence. Our data
      highlight the high frequency of active BKV infection after renal transplantation.
      Although high VL was detected in some patients, none developed a BKV nephropathy.
      A prospective follow-up of the whole population during the first year post renal
      transplantation is thus not useful to predict BKV disease.

PMID- 15996242
TI  - Early calcification of renal allografts detected by protocol biopsies: causes and
      clinical implications.
AB  - Interstitial calcification has been described in renal allografts, however, the
      etiology and significance of this finding for the graft are unclear. The aim of
      this study was to examine calcification in serial protocol biopsies, to test the
      hypothesis that calcification is related to parameters of calcium homeostasis in
      these patients and to analyze a possible relation between calcification and graft
      function at 1 year. We studied 213 patients with 586 protocol biopsies obtained 6
      weeks, 3 and 6 months after transplantation. Calcifications increased over time,
      from 6.1% at 6 weeks to 17.8% at 6 months. Out of the 213 patients, 56 had
      calcification in one or more biopsies. Patients age and gender, underlying renal
      disease, dialysis mode and duration, previous transplantations, donor type, age
      and gender, HLA matches and ischemia time had no influence on calcification.
      Calcification was not related to rejection episodes, acute tubular lesions,
      calcineurin inhibitor toxicity or tubulointerstitial fibrosis and tubular
      atrophy. Patients with calcification had significantly higher serum parathormone
      and calcium levels. In patients with calcification, high PTH levels correlated
      with an inferior outcome of graft function at 1 year after transplantation
      (p<0.05). Therefore, treatment of hyperparathyroidism should be considered
      earlier and more often in these patients.

PMID- 15996243
TI  - Coronary artery calcification in renal transplant recipients.
AB  - Cardiovascular disease is the leading cause of mortality in renal transplant
      recipients. Although renal transplant recipients frequently undergo cardiac
      functional tests prior to surgery, coronary atherosclerosis can remain
      undetected. Coronary artery calcification (CAC), an early marker of
      atherosclerosis can be quantified using EBCT. The purpose of this study was to
      determine the extent and characteristics of CAC at the time of renal
      transplantation. We evaluated 79 consecutive incident asymptomatic renal
      transplant recipients. Patients were mostly White (62%), male (54%) and had a
      deceased donor renal transplant (61%). The mean age was 47 (12.1) years. Sixty
      five percentage of subjects had CAC. The mean CAC score was 331.5 (562.4) with a
      median of 43.3. Older age, presence of diabetes, not having a preemptive
      transplant, deceased donor transplantation and hypercholesterolemia were
      significantly associated with presence of CAC univariately. Median CAC scores
      were significantly increased in subjects with diabetes (127.8 vs. 28.9, p=0.05),
      exposed to dialysis (102.9 vs. 3.7, p<0.001) and deceased donor recipients (169.7
      vs. 7.5, p=0.02). Using multiple logistic regression, age and time on dialysis
      were significantly associated with the presence of CAC at the time of transplant.
      In summary, CAC is prevalent in patients undergoing kidney transplant. CAC may be
      a method to identify renal transplant recipients at increased risk for future
      cardiovascular events.

PMID- 15996244
TI  - A retrospective assessment of pre-treatment variables on the response to
      darbepoetin alfa after renal transplantation.
AB  - This retrospective review assesses the efficacy of darbepoetin alfa for treating
      anemia after renal transplantation. Patients were evaluated over a 12-week
      period, and efficacy was based on achieving hemoglobin >12 g/dL. Thirty-six
      patients were analyzed (53% male, 53% cadaveric allografts, median age 42.5
      years). Baseline creatinine clearance ranged from approximately 15 to >100
      mL/min. Most patients initiated darbepoetin alfa <3 months (50%) or >12 months
      (44%) after transplantation, 19% were previously receiving recombinant human
      erythropoietin (rHuEPO), and 47% were on concomitant ACE inhibitors. The majority
      of patients received either tacrolimus- (53%) or cyclosporine- (44%) based
      immunosuppression. Overall, 29 (81%) patients achieved the hemoglobin target with
      a mean time to response of 4.4 weeks. Neither the time to anemia onset, previous
      rHuEPO therapy, concomitant ACE inhibitor, allograft source, immunosuppressive
      regimen, nor degree of renal function affected the proportion of patients
      achieving the hemoglobin target, time to response or darbepoetin alfa dose
      requirement. Patients with anemia >12 months post-transplantation or on
      concomitant ACE inhibitors required a significantly longer duration of therapy.
      No adverse events associated with darbepoetin alfa therapy were detected. These
      results demonstrate that darbepoetin alfa is a safe and effective treatment for
      anemia in renal transplant recipients.

PMID- 15996245
TI  - Similarities in skeletal muscle strength and exercise capacity between renal
      transplant and hemodialysis patients.
AB  - Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx)
      patients. Aim of the study was to assess to what extent exercise capacity and
      skeletal muscle strength of RTx patients differ from HD patients and healthy
      controls and to elucidate potential determinants of exercise capacity in RTx
      patients. Exercise capacity, muscle strength, lean body mass (LBM) and physical
      activity level (PAL) were measured by cycle-ergometry, isokinetic dynamometry,
      DEXA and Baecke Questionnaire, respectively, in 35 RTx, 16 HD and 21 controls.
      VO2peak and muscle strength of the RTx patients were significantly lower compared
      to controls (p<0.01), but not different compared to HD patients. In RTx patients,
      strength (p<0.001), PAL (p=0.001) and age (p=0.045) were significant predictors
      of VO2peak. Muscle strength was related to LBM (p=0.001) and age (p=0.001),
      whereas gender (p<0.001) and renal function (p=0.01) turned out to be significant
      predictors of LBM. No effects of corticosteroids were observed. Exercise capacity
      and muscle strength seem equally reduced in RTx and HD patients compared to
      controls. In RTx patients, muscle strength and PAL are highly related to exercise
      capacity. Renal function appears to be a significant predictor of LBM, and
      through the LBM, of muscle strength and exercise capacity.

PMID- 15996246
TI  - Laparoscopic donor distal pancreatectomy for living donor pancreas and pancreas
      kidney transplantation.
AB  - With the proliferation and expanding applications of laparoscopic techniques, we
      determined the applicability of the laparoscopic approach to living pancreas
      donation. We performed the first laparoscopic donor distal pancreatectomy in
      1999. We herein present our initial experience with five hand-assisted
      laparoscopic donor pancreatectomies. Three donors underwent distal pancreatectomy
      alone; two underwent a simultaneous left nephrectomy. The mean donor age was
      48.4+/-8.7 years with a body mass index of 23.7 kg/m2. The donor and recipient
      survival rate was 100% at up to 3 years of follow-up. There were no episodes of
      pancreatitis, leaks, or pseudocysts. All donors returned to their preoperative
      state of health and to work. None of the donors have required oral anti-diabetic
      medications or insulin. We conclude that laparoscopic donor distal pancreatectomy
      is a safe and efficient procedure; hand-assisted laparoscopic distal
      pancreatectomy appears to be preferable, because of the added margin of safety
      from increased tactile feedback and ease of pancreatic dissection. The procedure
      can be accomplished with a single 6-cm periumbilical incision and only two 12-mm
      ports, resulting in excellent cosmesis and high donor satisfaction.

PMID- 15996247
TI  - Pre-transplant IFN-gamma ELISPOTs are associated with post-transplant renal
      function in African American renal transplant recipients.
AB  - Final crossmatch testing is routinely used to assess the risk of antibody
      mediated graft injury/rejection post-transplant. Analogously, we postulated that
      quantitative measurements of anti-donor effector/memory T cells pre-transplant
      would independently assess post-transplant risk. To address this hypothesis, we
      determined the frequencies of pre-transplant, donor-specific interferon-gamma
      (IFN-gamma) enzyme-linked immunosorbent spots (ELISPOTs) and correlated the
      results with post-transplant outcomes in 37 African American recipients of
      deceased donor kidney transplants treated with tacrolimus- and sirolimus-based
      immunosuppression. A positive ELISPOT test (>25 spots/300,000 cells) was detected
      in 14 (38%) of 37 patients. The incidence of biopsy-proven acute rejection was
      50% (7/14) in ELISPOT-positive versus 17% (4/23) in ELISPOT-negative patients
      (p=0.036). Calculated glomerular filtration rate (MDRD) at 12 months was 37+/-16
      mL/min in ELISPOT-positive versus 55+/-20 mL/min in ELISPOT-negative patients
      (p=0.01). ELISPOT status remained a correlate of allograft function at 12 months
      by linear regression analysis (p=0.001), independent of rejection and other
      contributing variables. Pre-transplant donor-directed IFN-gamma ELISPOT
      assessment of anti-donor cellular immunity may function as a 'cellular
      crossmatch' and independently correlates with renal allograft function in African
      Americans receiving tacrolimus- and sirolimus-based immunosuppression.

PMID- 15996248
TI  - Avoidance of chronic steroid therapy in african american kidney transplant
      recipients monitored by surveillance biopsy: 1-year results.
AB  - African American (AA) kidney recipients receive chronic steroid therapy to
      improve outcomes, despite their high susceptibility to side effects, particularly
      diabetes and hypertension. This study evaluated the safety and efficacy of
      avoidance of chronic steroid therapy in AA compared to non-AA kidney recipients.
      Two hundred and six kidney recipients were studied; 103 AA recipients versus 103
      non-AA recipients. Induction was basiliximab and maintenance was a calcineurin
      inhibitor plus mycophenolate mofetil or sirolimus. Surveillance biopsies were
      preformed at 1, 6 and 12 months to assess subclinical acute rejection (SCAR) and
      chronic allograft nephropathy (CAN). Biopsy-proven acute rejection (AR) and SCAR
      were treated by methylprednisolone. The primary end point was AR. Secondary end
      points were graft function, 1-year patient and graft survival. AR was observed in
      16% of AA and 13% of non-AA recipients. SCAR at 1 month was significantly higher
      in the AA group (p=0.04). One-year actual patient and graft survival in the AA
      group was 96% and 88% and in the non-AA group 97% and 89%, respectively.
      Avoidance of chronic steroid therapy directed by surveillance biopsies provides
      equivalent AR, CAN and 1-year patient and graft survival in AA versus non-AA
      recipients and a 5% incidence of new onset diabetes mellitus. All recipients
      remain free of chronic steroid therapy. Longer-term follow-up is ongoing.

PMID- 15996249
TI  - Renal dysfunction is a strong and independent risk factor for mortality and
      cardiovascular complications in renal transplantation.
AB  - Renal transplant recipients (RTR) have shortened life expectancy, primarily due
      to premature cardiovascular disease (CVD). Traditional CVD risk factors are
      highly prevalent. In addition, several non-traditional risk factors may
      contribute to the high risk. The aim of the study was to evaluate the effects of
      renal dysfunction on mortality and cardiovascular complications in 1052 placebo
      treated patients of the Assessment of LEscol in Renal Transplantation (ALERT)
      trial. Follow-up was 5-6 years and endpoints included cardiac death, non
      cardiovascular death, all-cause mortality, major adverse cardiac event (MACE),
      non-fatal myocardial infarction (MI) and stroke. The effects of serum creatinine
      at baseline on these endpoints were evaluated. Elevated serum creatinine in RTR
      was a strong and independent risk factor for MACE, cardiac, non-cardiovascular,
      and all-cause mortality, but not for stroke or non-fatal MI alone. Serum
      creatinine was associated with increased mortality and MACE, independent of
      established CVD risk factors. Graft loss resulted in increased incidences of non
      cardiovascular death, all-cause mortality, MACE and non-fatal MI. In conclusion,
      elevated serum creatinine is a strong risk factor for all-cause, non
      cardiovascular and cardiac mortality, and MACE, independent of traditional risk
      factors, but not for stroke or non-fatal MI alone.

PMID- 15996250
TI  - Safety and adequacy of renal transplant protocol biopsies.
AB  - The protocol biopsy strategy has been criticized because of risks and marginal
      utility. We tested the risk. We performed 1171 protocol biopsies in 508 patients
      at 6, 12 and 26 weeks after renal transplantation, as well as 499 biopsies as
      indicated in 429 transplant patients. Biopsies were done as an outpatient
      procedure using an 18- or 16-gauge automated biopsy needle followed by 4 h bed
      rest. Complications were: gross hematuria 3.5%, perirenal hematomas 2.5%, arterio
      venous fistulas 7.3% and vasovagal reactions 0.5%. Major complications requiring
      invasive procedures such as blood transfusions or urinary catheter were seen in
      1% of cases. The hospitalization rate for observation was 1.9%. According to the
      Banff criteria of specimen adequacy, biopsies with 18-gauge needles yielded >7
      glomeruli and at least one artery in 53% of cases. Changing the needle size in
      October 2003, those biopsies done with 16-gauge needles yielded >7 glomeruli and
      at least one artery in 76% of cases, while the rate of major complications did
      not change. In conclusion, transplant protocol biopsies with 16-gauge needles
      provide better utility and similar risk as biopsies with 18-gauge needles. A 4-h
      recovery after biopsy appears adequate for discharge.

PMID- 15996251
TI  - Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in
      renal transplant recipients.
AB  - BK virus interstitial nephritis (BKVIN) is a serious complication after kidney
      grafting, necessitating drastic reduction of immunosuppressive therapy in order
      to enable viral clearance. Despite these measures, progressive graft dysfunction
      and graft loss occur in the majority of recipients. We diagnosed BKVIN in 21
      recipients grafted between 1998 and 2004. Eight of 21 patients were treated with
      weekly, adjuvant low-dose cidofovir in addition to reduction of immunosuppressive
      therapy. BKVIN caused irreversible deterioration of graft function in all
      patients but renal function stabilized after antiviral treatment (creatinine
      clearance: 51.8-32 mL/min; p=0.001) and no graft loss occurred in cidofovir
      treated recipients during 24.8 (8-41) months follow-up. Peak serum cidofovir
      concentrations were dose-dependent and attained approximately one-tenth of thein
      vitroEC50 for cidofovir against BK-virus, while pre-treatment with probenecid did
      not alter peak serum concentrations nor affected the incidence of nephrotoxicity.
      In fact, no cidofovir-related renal toxicity occurred; few patients had minor
      transient side effects (nausea, skin rash). In contrast, 9 of 13 patient who
      received no adjuvant cidofovir therapy lost their graft after median 8 (4-40)
      months. In this selected group of recipients with BKVIN, the use of adjuvant low
      dose cidofovir therapy resulted in prolonged graft survival and stabilized graft
      function.

PMID- 15996252
TI  - Adding sirolimus to tacrolimus-based immunosuppression in pediatric renal
      transplant recipients reduces tacrolimus exposure.
AB  - In adult renal recipients, coadministration of tacrolimus (TAC) and sirolimus
      (SIR) results in reduced exposure to TAC at SIR doses of 2 mg/day. Eight
      pediatric renal recipients (median age at transplant 2.0 years, range: 1.2-12.9
      years) were converted to TAC- and SIR-based immunosuppression as a rescue
      therapy. All patients had biopsy-proven chronic allograft nephropathy. TAC levels
      were measured using a commercially available EMIT assay and SIR levels with a
      newly developed assay based on the LC-MS MS technology. SIR was started at 0.13+/
      0.05 mg/kg/day (3.51+/-1.26 mg/m2/day) in two divided doses. TAC was given at
      0.14+/-0.09 mg/kg/day, resulting in a trough level of 6.3+/-2.5 ng/mL. After the
      addition of SIR, the median dose required to keep TAC blood trough concentrations
      within the target range increased by 71.2% (range: 21.9-245.4%), dose-normalized
      TAC exposure (AUC) decreased to 67.1% and the dose-normalized C(max), a surrogate
      for absorption rate, to 53.8% (both geometric means) while terminal half-life
      (t1/2), a pharmacokinetic parameter characterizing systemic elimination, remained
      unchanged (p<0.93). Adding SIR to TAC-based immunosuppression in young pediatric
      renal transplant recipients results in a significant decrease of TAC exposure.
      TAC trough levels should be monitored frequently.

PMID- 15996253
TI  - Infectious complications after heart transplantation in Chinese recipients.
AB  - Several factors appear to influence the incidence and type of infectious
      complications among different populations of transplant recipients. This study
      sought to assess the incidence and type of infection after transplantation in
      Chinese heart allograft recipients. A total of 130 infectious episodes occurred
      in 192 consecutive heart transplantation patients between June 1993 and May 2004.
      The median length of follow-up was 46.7+/-38.4 months. The 1-, 5- and 10-year
      survival rates were 81.8+/-2.8%, 63.0+/-3.8% and 45.7+/-7.7%. Infection was the
      leading cause of early and late deaths. Of the infectious episodes, 66 (51%) were
      caused by bacteria, 35 (27%) by viruses, 10 (8%) by fungi, 7 (5%) by
      Mycobacterium tuberculosis and 12 (9%) by other pathogens. The most common
      bacterial infectious episodes were caused by methicillin-resistant Staphylococcus
      aureus (20 of 66). The most common viral infections were varicella zoster virus
      infection in 12 (34%), cytomegalovirus infection in 9 (26%) and hepatitis B virus
      infection in 8 (23%). There was only one episode of clinical syndrome compatible
      to Pneumocystis jiroveci pneumonia. In conclusion, there was low incidence of
      Pneumocystis jiroveci pneumonia and cytomegalovirus infection, and high incidence
      of Mycobacterium tuberculosis infection in Chinese heart allograft recipients.

PMID- 15996254
TI  - Mychophenolate mofetil increased chagas disease reactivation in heart
      transplanted patients: comparison between two different protocols.
AB  - Heart transplantation (HT) remains the treatment of choice for advanced chagasic
      cardiomyopathy. New immunosuppression protocols have provided better control of
      rejection (RJ) and cardiac allograft vasculopathy. However, their influence on
      infection and Chagas disease reactivation (CDR) is not well established. The aim
      of this study was to compare the CDR rate in patients under two different
      immunosuppression protocols. We studied 39 chagasic patients who had undergone
      orthotopic HT between April, 1987 and June, 2004. They were divided into two
      groups, one taking azathioprine (group 1=24 patients) and the other taking
      mycophenolate mofetil (group 2=15 patients), in the standard doses (2 mg/kg/day
      and 2 g/day, respectively), beside prednisone and cyclosporine, in equivalent
      doses. The number of CDR and RJ episodes were analyzed in the first and second
      years after HT. CDR rates were 8%+/-5% at 1 year and 12%+/-6% at 2 years of
      follow-up in group 1. Otherwise, patients in group 2 presented CDR rates of 75%+/
      10% and 81%+/-9% at the same periods, respectively (p<0.0001, hazard ratio=6.06).
      When comparing RJ rates in the first year after HT, both groups had similar
      behavior under both immunosuppression protocols (p=0.88). These data show that
      current prescribed doses of mycophenolate mofetil increase the early risk of CDR
      without changing RJ incidence in this period.

PMID- 15996255
TI  - Minimal acute rejection after lung transplantation: a risk for bronchiolitis
      obliterans syndrome.
AB  - Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft
      dysfunction. Although previous studies have identified mild to severe rejection
      (grade>or=A2) as a risk factor for BOS, the role of minimal rejection (grade A1)
      remains unclear. To determine if A1 rejection by itself is a risk factor for BOS,
      we performed a retrospective cohort study on 228 adult lung transplant recipients
      over a 7-year period. Cohorts were defined by their most severe rejection episode
      (none, A1 only, and >or=A2) and analyzed for the subsequent development and
      progression of BOS using univariate and multivariate time-dependent Cox
      regression analysis. In the univariate model, the occurrence of isolated minimal
      rejection was a risk factor for all stages of BOS. Similarly, multivariate models
      that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral
      infection, underlying disease and type of transplant demonstrated that A1
      rejection was a distinct risk factor for BOS. Furthermore, the associated risk
      with A1 rejection was slightly greater than the risk from >or=A2 and treatment of
      A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that
      minimal rejection is associated with an increased risk for BOS development and
      progression that is comparable to A2 rejection.

PMID- 15996256
TI  - Clinical impact of community-acquired respiratory viruses on bronchiolitis
      obliterans after lung transplant.
AB  - Community-acquired viral respiratory tract infections (RTI) in lung transplant
      recipients may have a high rate of progression to pneumonia and can be a trigger
      for immunologically mediated detrimental effects on lung function. A cohort of
      100 patients was enrolled from 2001 to 2003 in which 50 patients had clinically
      diagnosed viral RTI and 50 were asymptomatic. All patients had nasopharyngeal and
      throat swabs taken for respiratory virus antigen detection, culture and RT-PCR.
      All patients had pulmonary function tests at regular intervals for 12 months.
      Rates of rejection, decline in forced expiratory volume (L) in 1 s (FEV-1) and
      bacterial and fungal superinfection were compared at the 3-month primary
      endpoint. In the 50 patients with RTI, a microbial etiology was identified in 33
      of 50 (66%) and included rhinovirus (9), coronavirus (8), RSV (6), influenza A
      (5), parainfluenza (4) and human metapneumovirus (1). During the 3-month primary
      endpoint, 8 of 50 (16%) RTI patients had acute rejection versus 0 of 50 non-RTI
      patients (p=0.006). The number of patients experiencing a 20% or more decline in
      FEV-1 by 3 months was 9 of 50 (18%) RTI versus 0 of 50 non-RTI (0%) (p=0.003). In
      six of these nine patients, the decline in FEV-1 was sustained over a 1-year
      period consistent with bronchiolitis obliterans syndrome (BOS). Community
      acquired respiratory viruses may be associated with the development of acute
      rejection and BOS.

PMID- 15996257
TI  - Islet transplantation in type 1 diabetes mellitus using cultured islets and
      steroid-free immunosuppression: Miami experience.
AB  - Following the success obtained with transplantation of fresh human islets under
      steroid-free immunosuppression, this trial evaluated the transplantation of
      islets that had undergone a period of in vitro culture and the potential of tumor
      necrosis factor (TNF-alpha) blockade to improve islet engraftment. Subjects
      included 16 patients with type 1 diabetes mellitus (T1DM); half were randomly
      assigned to receive Infliximab immediately preceding initial infusion.
      Immunosuppression consisted of daclizumab induction and sirolimus/tacrolimus
      maintenance. Out of 16 subjects 14 achieved insulin independence with one or two
      islet infusions; adverse events precluded completion in two. Without supplemental
      infusions, 11/14 (79%) subjects were insulin independent at 1 year, 6/14 (43%) at
      18 months; these same subjects remain insulin independent at 33+/-6 months. While
      on immunosuppression, all patients maintained graft function. Out of 14 patients,
      8 suffered chronic partial graft loss, likely immunological in nature, 5 of these
      received supplemental infusions. Currently, 11 subjects remain on
      immunosuppression, 8 (73%) are insulin independent, two with supplemental
      infusions. Insulin independent subjects demonstrated normalization of HbA1c,
      fructosamine and Mean Amplitude of Glycemic Excursions (MAGE) values. No clinical
      benefit of infliximab was identified. These results demonstrate that
      transplantation of cultured human islet allografts results in reproducible
      insulin independence in all subjects under this immunosuppressive regimen,
      comparable to that of freshly transplanted islets (Edmonton protocol).

PMID- 15996258
TI  - Adult liver transplant candidate attitudes toward graft sharing are not obstacles
      to split liver transplantation.
AB  - Split liver transplantation (SLT) benefits society by increasing the total number
      of transplants that can be performed, but it is yet unknown if a decreased post
      transplant survival (in comparison to whole liver transplantation) would make
      participation in SLT less appealing to adult liver transplant candidates. A 20
      item questionnaire was administered to 50 adult candidates to assess attitudes
      toward SLT and organ sharing. The overall attitudes of 60% of participants were
      classified as utilitarian (maximizing benefit to greatest number of candidates),
      while 26% were classified as self-preserving (maximizing individual benefit) and
      14% were undecided. Ninety percent of participants would be willing to share even
      if expected survival was less than that of whole liver transplantation, and 69%
      felt that pediatric candidates should have priority over adult candidates. In
      conclusion, attitudes toward graft sharing and the possibility of compromised
      survival benefit are not barriers to SLT for most adult liver transplant
      candidates.

PMID- 15996259
TI  - Human CD4+CD25+ regulatory T cells suppress anti-porcine xenogeneic responses.
AB  - Due to the shortage of human organs, xenotransplantation is being explored as an
      alternative to allotransplantation, but immune rejection remains a major hurdle
      to its implementation. We tested the ability of human CD4+CD25+ T cells (Treg
      cells) to suppress CD4+ T cell-mediated anti-porcine xenoresponses usingin
      vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and
      suppressed the proliferative response of CD4+CD25- T cells in a dose-dependent
      manner, and comparison of the allo- and xenoresponses indicated that more Treg
      cells might be required to suppress the xenogeneic response than the allogeneic
      response. Stimulation of CD4+CD25- T cells with porcine cells resulted in
      secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells
      suppressed the secretion of these cytokines, as well as the CD4+CD25- T-cell
      cytolytic response against porcine cells. These results suggest a potential role
      for Treg cells in promoting xenograft survival.

PMID- 15996260
TI  - Cryopreserved liver cell transplantation controls ornithine transcarbamylase
      deficient patient while awaiting liver transplantation.
AB  - Liver cell transplantation was performed in a child with urea cycle disorder
      poorly equilibrated by conventional therapy as a bridge to transplantation. A 14
      month-old boy with ornithine transcarbamylase (OTC) deficiency received 0.24
      billion viable cryopreserved cells/kg over 16 weeks. Tacrolimus and steroids were
      given as immunosuppressive treatment while the patient was kept on the pre-cell
      transplant therapy. Mean blood ammonia level decreased significantly following
      the seven first infusions, while urea levels started to increase from
      undetectable values. After those seven infusions, an ammonium peak up to 263
      microg/dL, clinically well tolerated, was observed. Interestingly, blood urea
      levels increased continuously to reach 25 mg/dL, after the last three infusions.
      Eventually, he benefited from elective orthotopic liver transplantation (OLT) and
      the post-surgical course was uneventful. We conclude that use of cryopreserved
      cells allowed short- to medium-term metabolic control and urea synthesis in this
      male OTC-deficient patient while waiting for OLT.

PMID- 15996261
TI  - Adenovirus tubulointerstitial nephritis presenting as a renal allograft space
      occupying lesion.
AB  - This report describes a case of adenovirus infection in a renal allograft 36 days
      after transplantation that presented with transient macroscopic hematuria,
      prominent systemic features and acute renal dysfunction. The patient had
      persistent high fevers despite broad antibiotic cover. A CT scan demonstrated a
      new discrete space occupying lesion in the allograft, which was devoid of blood
      flow on Doppler sonography. A targeted renal biopsy showed florid and focal
      necrotizing interstitial nephritis with intranuclear tubular viral inclusions.
      Treatment with ganciclovir and reduction in immunosuppression resulted in a rapid
      improvement. Immunohistochemistry and electron microscopy confirmed adenovirus
      infection. This case demonstrates an uncommon presentation of necrotizing
      adenoviral nephropathy, which should be considered in cases of renal allograft
      mass lesions.

PMID- 15996262
TI  - Cure of disseminated cryptococcal infection in a renal allograft recipient after
      addition of gamma-interferon to anti-fungal therapy.
AB  - The immunosuppressive regimens that are used in solid organ transplantation are
      potent inhibitors of Th0 as well as Th1 and Th2 cell-mediated immune responses.
      This predisposes patients to disseminated cryptococcal infections. Mortality in
      such patients remains very high despite advances in anti-fungal chemotherapy. We
      describe a case of disseminated cryptococcal disease in a renal allograft
      recipient that failed to respond to prolonged treatment with several anti-fungal
      drugs. However, addition of the immuno-modulator, interferon-gamma, resulted in
      the formation of granulomas and the resolution of his disease within 4-6 weeks.
      As we cannot find a similar example of combination therapy for disseminated
      cryptococcal disease in the solid organ transplant literature, we propose that
      interferon-gamma could be used in synergy with anti-fungal drugs to cure
      disseminated cryptococcal infections in solid organ transplant patients.

PMID- 15996263
TI  - Successful treatment of T-cell post-transplant lymphoproliferative disorder with
      the retinoid analog bexarotene.
AB  - T-cell post-transplant lymphoproliferative disorder (PTLD) is a rare life
      threatening complication of organ transplantation. It is usually resistant to
      treatment with reduction in immunosuppression or chemotherapy and carries a poor
      prognosis. We report on a combined kidney and pancreas transplant patient with
      Epstein-Barr virus (EBV) positive T-cell PTLD that had recurred after
      chemotherapy and reduction in immunosuppression. The patient was successfully
      treated with bexarotene, a novel synthetic retinoid analog, achieving a complete
      clinical response. Bexarotene may be a promising treatment for T-cell PTLD.

PMID- 15996264
TI  - Obstructive uropathy secondary to ureteral herniation in a pediatric en bloc
      renal graft.
AB  - Ureteral herniation is a rare entity. We report the first case of extraperitoneal
      ureteral herniation in a pediatric en bloc renal graft causing obstructive
      uropathy. A 70-year-old, obese patient with an en bloc renal transplant was found
      to have ureterohydronephrosis in the right renal graft on magnetic resonance
      imaging. Nephrostomy with insertion of a double-J catheter confirmed the presence
      of a ureteral loop within the inguinal tract. Surgery confirmed herniation of the
      ureter through the internal inguinal ring, crossing over the spermatic cord. We
      performed release, resection, ureteral reimplantation and hernioplasty. Four
      months later, renal function was normal and urinary tract dilation had
      diminished. This case illustrates an unusual cause of obstructive uropathy in a
      transplanted kidney. Apart from obesity, two other factors may have contributed
      to its development: presence of a redundant ureter, and the fact that the ureter
      had been placed over, rather than under, the spermatic cord.

PMID- 15996266
TI  - Lysis with Saponin improves detection of the response through CD203c and CD63 in
      the basophil activation test after crosslinking of the high affinity IgE receptor
      FcepsilonRI.
AB  - BACKGROUND: The basophil activation test (BAT), in which translocation of markers
      to the surface of blood basophils is measured in response to allergen by flow
      cytometry, is a rapid assay that is gaining popularity. Two markers are currently
      being evaluated for the BAT; CD63 and the lineage-specific CD203c. In a recent
      report, detection of CD203c after lysis with Saponin was shown to be superior to
      detection of CD63 after lysis with formic acid. We wanted to compare a) lysis
      with formic acid and lysis with Saponin, b) the response through CD203c and CD63,
      and c) the definition 10% activated cells above background with the probability
      binning metric T(chi) > 4, on sets of data generated with blood basophils
      stimulated with varying concentrations of anti-FcepsilonRI antibody. METHODS:
      Blood from volunteers was incubated with serial logarithmic dilutions of anti
      FcepsilonRI and subsequently with antibodies to CD203c PE and CD63 FITC. Sets of
      samples set up in parallel were lysed with either Saponin based Whole Blood
      Lysing reagent or with formic acid based Immunoprep/Q-prep. Samples were acquired
      on a FACS Calibur, but were compensated and analysed offline. Responders were
      defined as persons who had 10% or more activated basophils above background, or a
      T(chi) > 4, for two consecutive dilutions of anti-FcepsilonRI antibody. RESULTS:
      More basophils (median 1164 vs. median 397) and better discrimination of
      upregulated CD203c and CD63 amongst responders were obtained after lysis with
      Saponin than after lysis with formic acid. We suggest that CD203c may be a more
      sensitive marker for the BAT than CD63, as 6/11 responders were found with
      CD203c, compared with 3/11 with CD63. Most responders (7/11) were identified with
      probability binning. CONCLUSION: A combination of lysis with Saponin and the
      markers CD203c and CD63 computed by probability binning may be the most sensitive
      method of detecting activation of basophils after stimulation through
      FcepsilonRI.

PMID- 15996267
TI  - Familial breast cancer: characteristics and outcome of BRCA 1-2 positive and
      negative cases.
AB  - BACKGROUND: The clinical and pathological characteristics and the clinical course
      of patients with breast cancer and BRCA 1-2 mutation are poorly known. METHODS:
      From 1997, patients with breast cancer and a family history of breast or ovarian
      cancer were offered BRCA testing. The clinical and pathological features of
      patients with known BRCA status were retrospectively assessed and comparisons
      were made between cancers arising in BRCA positive and BRCA wild type (WT)
      patients respectively. Type of treatment, pattern of relapse, event (local
      relapse, contralateral breast cancer, metastases) free and overall survival were
      also compared in the two groups. Out of the 210 patients tested, 125 had been
      treated and followed-up at our Institution and were evaluated in this study.
      RESULTS: BRCA positive patients tended to be more often premenopausal (79% vs
      65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours
      (76% vs 40%--p = 0.002 at univariate analysis, not significant at multivariate
      analysis) and negative estrogen receptors (43% vs 29%). Treatment was not
      different in the two groups. In the 86 BRCA-WT patients, the first event was a
      local relapse in 3 (3%), metachronous contralateral breast cancer in 7 (8%) and
      distant metastases in 16 (19%). In the 39 BRCA positive patients, the
      corresponding figures were 3 (8%), 8 (21%) and 3 (8%). There was no difference in
      event free survival, with a median of 180 months in both groups of patients. At
      20 years, projected survival was 85% for BRCA positive patients and 55% for BRCA
      WT, but this difference was not statistically significant. CONCLUSION: Although
      BRCA positive patients have more frequently negative prognostic factors, their
      prognosis appears to be equal to or better than in patients with BRCA-WT.

PMID- 15996268
TI  - Action ethical dilemmas in surgery: an interview study of practicing surgeons.
AB  - BACKGROUND: The aim of this study was to describe the kinds of ethical dilemmas
      surgeons face during practice. METHODS: Five male and five female surgeons at a
      University hospital in Norway were interviewed as part of a comprehensive
      investigation into the narratives of physicians and nurses about ethically
      difficult situations in surgical units. The transcribed interview texts were
      subjected to a phenomenological-hermeneutic interpretation. RESULTS: No gender
      differences were found in the kinds of ethical dilemmas identified among male and
      female surgeons. The main finding was that surgeons experienced ethical dilemmas
      in deciding the right treatment in different situations. The dilemmas included
      starting or withholding treatment, continuing or withdrawing treatment,
      overtreatment, respecting the patients and meeting patients' expectations. The
      main focus in the narratives was on ethical dilemmas concerning the patients'
      well-being, treatment and care. The surgeons narrated about whether they should
      act according to their own convictions or according to the opinions of principal
      colleagues or colleagues from other departments. Handling incompetent colleagues
      was also seen as an ethical dilemma. Prioritization of limited resources and
      following social laws and regulations represented ethical dilemmas when they
      contradicted what the surgeons considered was in the patients' best interests.
      CONCLUSION: The surgeons seemed confident in their professional role although the
      many ethical dilemmas they experienced in trying to meet the expectations of
      patients, colleagues and society also made them professionally and personally
      vulnerable.

PMID- 15996269
TI  - Colocalization of endogenous TNF with a functional intracellular splice form of
      human TNF receptor type 2.
AB  - BACKGROUND: Tumor necrosis factor (TNF) is a pleiotropic cytokine involved in a
      broad spectrum of inflammatory and immune responses including proliferation,
      differentiation, and cell death. The biological effects of TNF are mediated via
      two cell surface TNF receptors: p55TNFR (TNFR1; CD120a) and p75TNFR (TNFR2;
      CD120b). Soluble forms of these two receptors consisting of the extracellular
      domains are proteolytically cleaved from the membrane and act as inhibitors. A
      novel p75TNFR isoform generated by the use of an additional transcriptional start
      site has been described and was termed hicp75TNFR. We focused on the
      characterization of this new isoform as this protein may be involved in chronic
      inflammatory processes. METHODS: Cell lines were retroviraly transduced with
      hp75TNFR isoforms. Subcellular localization and colocalization studies with TNF
      were performed using fluorescence microscopy including exhaustive photon
      reassignment software, flow cytometry, and receptosome isolation by magnetic
      means. Biochemical properties of the hicp75TNFR were determined by affinity
      chromatography, ELISA, and western blot techniques. RESULTS: We describe the
      localization and activation of a differentially spliced and mainly
      intracellularly expressed isoform of human p75TNFR, termed hicp75TNFR. Expression
      studies with hicp75TNFR cDNA in different cell types showed the resulting protein
      mostly retained in the trans-Golgi network and in endosomes and colocalizes with
      endogenous TNF. Surface expressed hicp75TNFR behaves like hp75TNFR demonstrating
      susceptibility for TACE-induced shedding and NFkappaB activation after TNF
      binding. CONCLUSION: Our data demonstrate that intracellular hicp75TNFR is not
      accessible for exogenously provided TNF but colocalizes with endogenously
      produced TNF. These findings suggest a possible intracellular activation
      mechanism of hicp75TNFR by endogenous TNF. Subsequent NFkappaB activation might
      induce anti-apoptotic mechanisms to protect TNF-producing cells from cytotoxic
      effects of TNF. In addition, the intracellular and not TACE-accessible splice
      form of the hp75TNFR could serve as a pool of preformed, functional hp75TNFR.

PMID- 15996270
TI  - Genetic and spectrally distinct in vivo imaging: embryonic stem cells and mice
      with widespread expression of a monomeric red fluorescent protein.
AB  - BACKGROUND: DsRed the red fluorescent protein (RFP) isolated from Discosoma sp.
      coral holds much promise as a genetically and spectrally distinct alternative to
      green fluorescent protein (GFP) for application in mice. Widespread use of DsRed
      has been hampered by several issues resulting in the inability to establish and
      maintain lines of red fluorescent protein expressing embryonic stem cells and
      mice. This has been attributed to the non-viability, or toxicity, of the protein,
      probably as a result of its obligate tetramerization. A mutagenesis approach
      directing the stepwise evolution of DsRed has produced mRFP1, the first true
      monomer. mRFP1 currently represents an attractive autofluorescent reporter for
      use in heterologous systems. RESULTS: We have used embryonic stem cell-mediated
      transgenesis to evaluate mRFP1 in embryonic stem cells and mice. We find that
      mRFP1 exhibits the most spatially homogenous expression when compared to the
      native (tetrameric) and variant dimeric forms of DsRed. High levels of mRFP1
      expression do not affect cell morphology, developmental potential or viability
      and fertility of animals. High levels of widespread mRFP1 expression are
      maintained in a constitutive manner in embryonic stem cells in culture and in
      transgenic animals. We have used various optical imaging modalities to visualize
      mRFP1 expressing cells in culture, in embryos and adult mice. Moreover co
      visualization of red, green and cyan fluorescent cells within a sample is easily
      achieved without the need for specialized methodologies, such as spectral
      deconvolution or linear unmixing. CONCLUSION: Fluorescent proteins with
      excitation and/or emission profiles in the red part of the visible spectrum
      represent distinct partners, or longer wavelength substitutes for GFP. Not only
      do DsRed-based RFPs provide a genetically and spectrally distinct addition to the
      available repertoire of autoflorescent proteins, but by virtue of their spectral
      properties they permit deeper tissue imaging. Our work in generating CAG::mRFP1
      transgenic ES cells and mice demonstrates the developmental neutrality of mRFP1
      in an organismal context. It paves the way for the use of DsRed-based monomeric
      RFPs in transgenic and gene targeted approaches which often necessitate spatially
      and/or temporally restricted reporter expression. Moreover animals of the
      CAG::mRFP1 transgenic strain serve as a source of RFP tagged tissue for the
      derivation of cell lines and explant, transplant and embryo chimera experiments.

PMID- 15996272
TI  - [To ameliorate early postburn internal organ injury by improving early fluid
      resuscitation].

PMID- 15996273
TI  - [The effect of hyperoxic Ringer's solution on the rabbits with inhalation injury
      at early postburn stage].
AB  - OBJECTIVE: To investigate the effect of hyperoxic Ringer's solution on inhalation
      injury given at early postburn stage in rabbit. METHODS: Seventy-seven rabbits
      were randomly divided into four groups, i.e. A (normal control, n = 5, without
      injury), B (n = 24, with Ringer's solution infusion for 10 days after injury), C
      (n = 24, with hyperoxic Ringer's solution infusion for 10 days after injury) and
      D (n = 24, without treatment after injury) groups. The rabbits in B, C and D
      groups were observed on 1 post injury day (PID), 2 PID, 3 PID, 5 PID, 7 PID and
      10 PID, with 4 in each time points. The vital signs and survival rate were
      observed and the blood gas analysis, the WBC and PMN in the peripheral blood,
      ratio of wet/dry weight (W/D) of the lung tissue, the MDA, SOD contents in the
      pulmonary tissue, and the pulmonary pathomorphology were determined by
      corresponding methods. RESULTS: The respiratory rate of the rabbits increased
      postburn, which was accompanied with gasping breath, flapping of nasal alae,
      frequent cough, and increased buccal and nasal secretion. Dry and wet rales were
      heard in the lungs after injury. The survival rate in D, B and C groups was
      13.3%, 27.8% and 65.6%, respectively. Metabolic acidosis was identified in these
      groups by blood gas analysis. The indices of PaCO2, WBC, PMN, W/D, MDA in B, C
      and D groups were higher than those in A group in the order of D > B > C > A
      groups. While the pH, PaO2 value and SOD content in D group were lower than those
      in A group in the order of D < B < C < A groups (P < 0.05). Pathomorphological
      examination revealed that pulmonary volume increased after the injury with
      microscopic inflammatory changes in pulmonary tissue in B, C and D groups. While
      the extent and degree of injury in C group after the treatment of hyperoxic
      Ringer's solution were evidently less severe than those in other groups.
      CONCLUSION: Early administration of hyperoxic Ringer's solution during the early
      postburn stage could be beneficial to the management of inhalation injury.

PMID- 15996271
TI  - Vasculature deprivation--induced osteonecrosis of the rat femoral head as a model
      for therapeutic trials.
AB  - EXPERIMENTAL OSTEONECROSIS: The authors' experience with experimentally produced
      femoral capital osteonecrosis in rats is reviewed: incising the periosteum at the
      base of the neck of the femur and cutting the ligamentum teres leads to
      coagulation necrosis of the epiphysis. The necrotic debris is substituted by
      fibrous tissue concomitantly with resorption of the dead soft and hard tissues by
      macrophages and osteoclasts, respectively. Progressively, the formerly necrotic
      epiphysis is repopulated by hematopoietic-fatty tissue, and replaced by
      architecturally abnormal and biomechanically weak bone. The femoral heads lose
      their smooth-surfaced hemispherical shape in the wake of the load transfer
      through the hip joint such that, together with regressive changes of the joint
      cartilage and inflammatory-hyperplastic changes of the articular membrane, an
      osteoarthritis-like disorder ensues. THERAPEUTIC CHOICES: Diverse therapeutic
      options are studied to satisfy the different opinions concerning the significance
      of diverse etiological and pathogenic mechanisms: 1. Exposure to hyperbaric
      oxygen. 2. Exposure to hyperbaric oxygen and non-weight bearing on the operated
      hip. 3. Medication with enoxaparin. 4. Reduction of intraosseous hypertension,
      putting to use a procedure aimed at core decompression, namely drilling a channel
      through the femoral head. 5. Medication with vascular endothelial growth factor
      with a view to accelerating revascularization. 6. Medication with zoledronic acid
      to decrease osteoclastic productivity such that the remodeling of the femoral
      head is slowed. Glucocorticoid-related osteonecrosis appears to be apoptosis
      related, thus differing from the vessel-deprivation-induced tissue coagulation
      found in idiopathic osteonecrosis. The quantities of TNF-alpha, RANK-ligand and
      osteoprotegerin are raised in glucocorticoid-treated osteoblasts so that the
      differentiation of osteoclasts is blocked. Moreover, the osteoblasts and
      osteocytes of the femoral cortex mostly undergo apoptosis after a lengthy period
      of glucocorticoid medication.

PMID- 15996275
TI  - [Influence of pinacidil on the myocardial mitochondrial structure and the
      respiratory function in scalded rats].
AB  - OBJECTIVE: To investigate the influence of pinacidil preconditioning on the
      protection of the structure and respiratory function of injured myocardial
      mitochondria in scalded rats. METHODS: Seventy-five healthy Wistar rats, weighed
      250 approximately 300 g, were randomly divided into three groups: i.e. control (n
      = 9, with intraperitoneal injection of 50 microg/kg isotonic saline), scald (n =
      33, with 30% TBSA full thickness scald) and pre-conditioning (n = 33, with same
      extent of scald injury after intraperitoneal injection of 50 microg/kg pinacidil)
      groups. Mitochondrial ultrastructure was observed by transmission electron
      microscope. The mitochondrial respiratory function, the MDA content and the
      superoxide anion level were determined with corresponding methods. RESULTS: The
      degree of injury to rat myocardial mitochondria in pre-conditioning group was
      less intensive than that in scald group (P < 0.05 or 0.01). The respiratory
      control rate in pre-conditioning group was obviously higher than that in scald
      group (P < 0.05), and the contents of MDA and superoxide anion in pre
      conditioning group were markedly lower than those in scald group (P < 0.05 or
      0.01), as evidenced by their contents at 3 post scalding hours (0.60 +/- 0.09
      micromol/g and 0.127 +/- 0.020) were obviously lower than those in scald group
      (0.83 +/- 0.07 micromol/g and 0.169 +/- 0.015) (P < 0.01). CONCLUSION: Pinacidil
      preconditioning was beneficial in the protection of myocardial mitochondria in
      scalded rats, and it might be related to the pre-opening of potassium channel
      which was sensitive to mitochondrial ATP.

PMID- 15996276
TI  - [Protective effects of taurine on myocardial injury in severely burned rats].
AB  - OBJECTIVE: To investigate the effect of taurine on myocardial injury in severely
      scalded rats. METHODS: A total of 130 healthy adult Wistar rats were randomly
      divided into 3 groups: the control group (C, without burns), the burn group (B,
      subjected to a 30% TBSA III degree scalding) and the treatment group (T, treated
      with intraperitoneal injection of taurine (400 mg/kg) immediately after scald
      injury). The plasma and myocardial tissue samples in B and T groups were
      harvested at 1, 3, 6, 12, 24 and 48 postburn hours (PBH) for the determination of
      the contents of cardiac troponin T (cTnT), malondialdehyde (MDA), tumor necrosis
      factor-alpha (TNF-alpha), and angiotensin II (AngII) in plasma, and the contents
      of TNF-alpha, AngII and calcium ion in myocardial tissue. The morphological
      change in the myocardial tissue was observed with transmission electronic
      microscope (TEM) and was compared with that in C group. The changes in the plasma
      TNF-alpha and AngII were analyzed in relation to that of plasma cTnT. RESULTS:
      The plasma cTnT content in B group at 3 PBH was markedly higher than that in C
      group (0.16 +/- 0.03 microg/L) (P < 0.01), and it peaked (6.32 +/- 0.41) at 12
      PBH and remained at high level at 48 PBH. While the plasma MDA content and the
      calcium ion level in B group were evidently higher than those in C group during 3
      to 48 PBH (P < 0.01). The TNF-alpha contents in plasma and myocardial tissue
      during 6 to 48 PBH were significantly higher than those in C group (P < 0.01).
      The AngII contents in plasma and myocardial tissue during 3 to 24 PBH were
      obviously higher than those in C group (P < 0.01). All the indices in T group
      were significantly lower than those in B group (P < 0.01). Histological
      examination revealed that there was myocardial damage in various degrees during
      early postburn stage in B group, such as focal dissolution and fragmentation of
      myofilament, mitochondrial edema, myocyte sarcoplasmic protrusions like piano
      keys. But all the above changes in T group were evidently ameliorated to near
      normal. There was close positive correlation between the change in the
      concentrations of plasma content of TNF-alpha and AngII and cTnT in B group (r =
      0.87 and 0.82, P < 0.05). CONCLUSION: The production of TNF-alpha, MDA, cTnT,
      AngII and high calcium ion level of myocardiocytes in severely burned rats can be
      inhibited by taurine, which was beneficial in the management of myocardial injury
      after severe burns.

PMID- 15996277
TI  - [The effects of burn serum on the erythropoiesis and granulopoiesis in bone
      marrow in mice].
AB  - OBJECTIVE: To observe the effects of burn serum on the erythropoiesis and
      granulopoiesis in bone marrow in mice, and to explore the possible underlying
      mechanism. METHODS: Murine bone marrow cell (BMC) strain was prepared routinely
      and was employed in the establishment of the culture system of colony forming
      units of erythrocytes, or granulocytes and monocytes. To both sets of culture
      system normal murine serum (N group) and burn serum, which was collected from the
      mice with 15% full thickness burn at 12 postburn hours (PBH) and 1, 3, 5, 7 and
      10 postburn days (PBD), (burn serum group) was added. In addition, positive
      control and blank control groups were set accordingly. The stimulating activity
      of all kinds of sera on the BMCs in the two sets of culture system was
      determined. The changes in the burn serum concentrations of EPO and GM-CSF were
      detected by radioimmunoassay, and the data were analyzed by logarithmic linear
      fitting correlation with the former influence of burn sera on the erythrocytes
      and granulocytes. RESULTS: (1) Burn sera exhibited obvious stimulation promoting
      activity on the erythropoiesis and granulopoiesis in BMC, and the activity peaked
      (384 +/- 60 and 127 +/- 16 CFU) on 1 PBD and decreased thereafter to approach the
      values found in normal sera group (125 +/- 14 and 34 +/- 20 CFU) on 7 PBD. (2)
      The EPO content in burn serum was evidently higher than the normal value (P <
      0.01) during 12 PBH to 7PBD period. The GM-CSF concentration was obviously higher
      than the normal value (P < 0.05) at 12 PBH and on 1 PBD. (3) The EPO
      concentration in burn serum was significantly and logarithmically correlated with
      the stimulation promoting activity of burn serum on erythropoiesis (r = 0.8570, P
      = 0.0137). But the GM-CSF concentration in culture with burn serum was not
      correlated with the stimulation promoting activity of burn serum on
      granulopoiesis (r = 0.7049, P > 0.05). CONCLUSION: The sera harvested from burned
      mice during early postburn stage exhibited strong stimulation promoting activity
      on the erythropoiesis and granulopoiesis in bone marrow. The increased EPO level
      in burn serum might be the important factor contributing strong stimulation
      action on erythropoiesis, while increased GM-CSF level was not.

PMID- 15996278
TI  - [Role of Rho kinase in reorganization of the vascular endothelial cytoskeleton
      induced by rat burn serum].
AB  - OBJECTIVE: To investigate the changes in endothelial cytoskeletal reorganization
      and the role of Rho in the signal transduction pathway. METHODS: ECV304 cells
      were cultured and randomly divided into following groups: i.e. sham (with normal
      rat serum treatment), burn (with burn rat serum treatment), Y (with 30 micromol/L
      Rho kinase inhibitor Y-27632 treatment), burn plus Y (pretreatment of cells with
      burn serum before treated with 30 micromol/L Y-27632), Y plus burn (pretreatment
      of cells with Y-27632 for 1 hour before treated with burn serum), LPA (with
      normal rat serum and 13 micromol/L LPA), and LPA plus Y (pretreatment of cells
      with LPA before treated with Y-27632) groups. The indices were examined at 6, 7
      and 8 posttreatment hours (PTH) in all groups except in Y group. The endothelial
      morphology was observed with HE staining. Endothelial cytoskeleton was observed
      by dual-fluorescence labeling of filamenta (F) with Rhodamine-phalloidin and
      monomer (G) with oregon green labeled DNAase. The actin content in the cells in
      all groups was measured with flow cytometry. RESULTS: In sham and control group,
      the cells were in fusiform or polygonal shape, with satisfactory growth;
      filamentous actin (F-actin) was mainly distributed in the peripheral site of the
      cytoplasm and formed peripheral filamental band. The cells became confluent to
      form a single layer with reticular structure. Globular actin (G-actin) was
      concentrated in the nucleus and per nucleus. In burn group, after 6 hours of burn
      serum treatment, the ability of cells to adhere to vessel wall was weakened, and
      a striking reorganization of the actin cytoskeleton and the formation of the
      stress fibers were found. Furthermore, the fluorescent intensity of the
      peripheral filament bands was weakened, and dispersed actin monomers were seen in
      the cytoplasm. This reaction was enhanced along with elapse of stimulation time.
      In burn plus Y or Y plus burn group, the cells grew and adhered well to the wall
      of culture vessel. The distribution of the filamentous actin was the same as the
      sham group, while the stress fiber decreased in amount obviously. The structure
      of globular actin was condensed with little G-actin in the cytoplasm. The changes
      in actin cytoskeleton in LPA group was similar to that in burn group. The effects
      of LPA on actin reorganization could also be reversed by Y-27632. The content of
      F-actin in burn group at 6 PTH (0.63 +/- 0.07) was lower than that in sham group
      (0.75 +/- 0.08), while the content of G-actin in burn group (1.28 +/- 0.27) was
      higher than that in sham group (1.16 +/- 0.16, P > 0.05). CONCLUSION: Burn serum
      induces vascular endothelial actin cytoskeleton reorganization in endothelial
      cells via the Rho-dependent signal pathway. Similar to the effect of LPA, this
      effect could be reversed by Y-27632.

PMID- 15996279
TI  - [Experimental study on the skeletal muscle reconstruction with autologous fascia
      as a scaffold].
AB  - OBJECTIVE: To explore the feasibility of autologous fascia as a scaffold for the
      reconstruction of skeletal muscle in vivo. METHODS: Twenty-eight healthy New
      Zealand rabbits were employed in the study. The anterior tibial muscle in both
      legs were divided to create a gap of 10 mm in each muscle. One leg was used in
      the experiment (E, n = 28), while the contralateral as self-control (C). The legs
      in C group were further divided into 3 groups (C1, C2 and C3). While defects in
      the midportion of anterior tibial muscle in the hind legs were created in all
      rabbits. In E group, each defect was filled with a tubule made of autologous
      fascia lata, and the fascial tubule was filled with tiny muscular granules (< 1
      mm x 1 mm x 1 mm). In C1 group (n = 10), the defect was also filled with fascial
      tubule but with no muscle filling. The defect in C2 group (n = 10) was only
      filled with muscle granules without fascial tubule. The defect in C3 group (n =
      8) received no treatment. The survival rate of the transplantation was grossly
      observed, and the tissue samples were harvested for histological and ultra
      structural examination and immunohistochemical identification of desmin at 2, 3,
      4, 6 and 9 post-operation weeks. The expression level of alpha-actin DNA in the
      tissue samples from the midportion of grafted fascia was assessed by RT-PCR
      (reverse transcription polymerase chain reaction) in E and C1 groups. RESULTS:
      (1) Survival rate of the transplantation: In E group, it was 93.33% with near
      normal tissue contour in the grafting area. The muscle defects were not
      completely repaired in C1, C2 and C3 groups. (2) Under light and electronic
      microscopy, marked proliferation of muscular cells surrounding fibrous tissue
      could be discerned at 2 and 3 post-operation weeks in E group, while only
      necrotic tissue and fibrosis were observed in C1 and C2 groups, and no definite
      tissue could be discernible in C3 group. (3) Immunohistochemical staining
      revealed that over 85% of the cells were positive for desmin in E group, while
      only less than 25% in C1 group. (4) The expression level of alpha-actin DNA was
      significantly higher in E group than that in C2 group (P < 0.05). CONCLUSION:
      These results suggested that autologous fascia as a scaffold is beneficial for
      skeletal muscle reconstruction in vivo.

PMID- 15996281
TI  - [Experimental study on the antagonistic activity of cationic multi-peptide
      mastoparan-1 against lipopolysaccharide].
AB  - OBJECTIVE: To explore the mechanism of cationic multi-peptide mastoparan-1 (MP-1)
      on the protection of mice from lipopolysaccharide (LPS) challenge. METHODS:
      Thirty Kunming mice were divided randomly into MP-1, injury, protection groups
      with 10 mice in each group. The mice in MP-1 group were injected with 3 mg/kg MP
      1 by tail vein, while those in injury group were injected with 20 mg/kg LPS by
      tail vein, and those in protection group 3 mg/kg MP-1 within 20 seconds after 20
      mg/kg LPS injection were injected. The effects of MP-1 on the protection of mice
      from LPS challenge were observed. In vitro, the affinity of MP-1 and PMB to LPS
      was compared by biosensor and FAST fit construct and expressed as Kd. And the
      neutralizing activity of MP-1 and PMB in dose of 5, 10, 20, 40 micromol/L on LPS
      (2 microg/L) was detected by dynamic turbidimetric limulus test with LPS
      neutralizing 0 micromol/L MP-1 and PMB as control. The mRNA expression levels of
      TLR4, TNF-alpha and IL-6 in murine peritoneal macrophages (PM phi) after exposure
      to LPS (100 ng/ml) were assayed by RT-PCR. RESULTS: MP-1 could significantly
      protect mice from LPS challenging with protection rate of 90%. In vitro, MP-1 had
      a high affinity (Kd value: 484.0 nmol/L) and neutralizing ability with LPS, but
      it was lower than that of PMB (Kd value: 18.9 nmol/L). The neutralizing effect of
      20 and 40 micromol/L MP-1 was obviously stronger than that in 0 micromol/L (P <
      0.01). MP could obviously inhibit the expression of TLR4, TNF-alpha and IL-6 mRNA
      in LPS-stimulated murine PM phi. CONCLUSION: MP-1 can evidently protect mice from
      lethal LPS challenge, and the mechanism might be related to the activity of MP-1
      which binding and neutralizing LPS, blocking the combination LPS with its
      receptors. So the murine macrophage activation induced by LPS was inhibited.

PMID- 15996283
TI  - [Expression of keratinocyte basement membrane related genes during the process of
      re-epithelialization of burn wound in scalded rats].
AB  - OBJECTIVE: To study the expression of keratinocyte (KC) basement membrane (BM)
      related genes during the process of re-epithelialization of burn wound in scalded
      rats with cDNA microarray technique. METHODS: Twenty-four SD rats were inflicted
      with deep partial thickness scald with an area of 45 cm(2) on the back, and they
      were randomly divided into A [3 postscald day (PSD)], B (10 PSD), C (14 PSD) and
      D (re-epithelialization complete day) groups, with 6 rats in each group. Tissue
      samples were harvested from 1 cm of wound margin on 3, 10 and 14 PSD. On the re
      epithelialization complete day, tissue samples were harvested from the center of
      the wound in D group and digested with enzyme into KC suspensions. Skin samples
      from the back of 6 uninjured rats were taken as normal control. The differential
      expression of KC BM related genes during different stages of re-epithelialization
      was assayed with cDNA microarray. RESULTS: The expression of laminin (LN) gamma 1
      (2.068) and integrin beta8 (2.200) was up-regulated on 3 PSD compared with that
      in control. The expression of integrin beta1 and LN receptor 1 was up-regulated
      on 10 and 14 PSD, (2.472 and 2.658), while that of integrin beta2 and beta1
      (0.419 and 0.462) down-regulated on 10 and 14 PSD, and the expression of type IV
      collagen alpha1 and alpha3 was up-regulated during re-epithelialization.
      CONCLUSION: The expression of integrin beta1, LN gamma 1, LN receptor 1, type IV
      collagen alpha1 and alpha3 genes were up-regulated during re-epithelialization,
      which might be beneficial to the construction of BM in new skin and the formation
      of stable conjunction between KC and BM.

PMID- 15996285
TI  - [The use of superficial cervical artery island skin flaps in the repair of the
      maxillofacial and cervical scar].
AB  - OBJECTIVE: To investigate the method of harvesting of superficial cervical artery
      island skin flap, and its clinical application in the repair of the maxillofacial
      and cervical scars. METHODS: The origin, course, branches and distribution of the
      superficial cervical artery were studied in 10 adult cadavers. The superficial
      cervical artery could be divided into three segments: i.e. the segment before
      entering the trapezius muscle, the segment in the trapezius muscle, and the
      segment emerging from the trapezius muscle. Fourteen patients with maxillofacial
      and cervical scar contracture were enrolled in the study. The postburn scars were
      removed, and the wounds were covered by superficial cervical artery island skin
      flaps. The survival of the flap after the operation and the recovery of the neck
      movements were observed. RESULTS: The length of superficial cervical artery
      before entering the trapezius muscle was 5.1 +/- 0.4 cm, while that inside the
      trapezius muscle was 2.1 +/- 0.5 cm, and that after emerging from the trapezius
      muscle was 4.7 +/- 0.7 cm, respectively. The internal perforating branch was
      located 7.3 +/- 0.6 cm beside the seventh cervical vertebrae, and 3.9 +/- 0.7 cm
      above the spine of scapula. The flap was from 16 cm x 7 cm to 35 cm x 12 cm in
      size. All the flaps survived, except one with partial necrosis in the distal part
      (3.0 cm x 1.5 cm) of the flap. Follow-up observation for 4 months to 3 years
      showed satisfactory results. CONCLUSION: Superficial cervical artery island skin
      flap is simple in the flap preparation, and there is no necessity to cut the
      pedicle, thus it is particularly suitable for the reconstruction of severe
      postburn maxillofacial and cervical contracture.

PMID- 15996286
TI  - [Influence of macrophages on the expression of vascular endothelial growth factor
      receptor mRNA, homeobox B2 mRNA, and integrin alpha nu beta3 in vascular
      endothelial strain].
AB  - OBJECTIVE: To investigate the influence of macrophages on the expression of the
      vascular endothelial growth factor (VEGF) receptor (KDR) mRNA, homeobox B2
      (HOXB2) mRNA, and integrin alpha nu beta3 in vitro in vascular endothelial
      strain. METHODS: Human umbilical vein cells (ECV304) were cultured in vitro and
      divided into 4 groups, i.e. (1) ECV304 group, (2) ECV304 + conA group [with conA
      (25 microg/ml in culture) added to ECV304], (3) ECV304 + U937 group (with 1 x
      10(5)/ml of U937 cells added to 1 x 10(5)/ml ECV 304), (4) ECV304 + U937 + conA
      group [with 1 x 10(5)/ml of U937 cells and conA (25 microg/ml in culture)]
      groups. Forty-eight hours after culturing, the expression of integrin receptor
      alpha nu beta3 and the changes in the expression of KDR mRNA and HOXB2 mRNA in
      each group were determined by immunofluorescent technique and RT-PCR,
      respectively. RESULTS: The expression of integrin receptor alpha nu beta3, KDR
      mRNA, and HOXB2 mRNA in ECV304 group were 6.7 +/- 1.5, 0.633 +/- 0.012, and 0.674
      +/- 0.004, respectively, while those in ECV304 + U937 + conA group (10.2 +/- 1.7,
      0.879 +/- 0.003, 0.947 +/- 0.003) were obviously more upregulated when compared
      with those in ECV304 group (P < 0.01). No difference in the above indices was
      found between ECV304 and ECV304 + conA, ECV304 + U937 groups (P > 0.05).
      CONCLUSION: Macrophages activated by ConA can accelerate the proliferation,
      migration and adhesion to the basement membrane matrix of vascular endothelial
      cells through the influence on the expression of KDR mRNA, HOXB2 mRNA and
      integrin alpha nu beta3, and through this pathway the angiogenesis is modulated.

PMID- 15996288
TI  - [Influence of vascular endothelial growth factor gene modification on skin
      substitute grafted on nude mice].
AB  - OBJECTIVE: To investigate the influence of vascular endothelial growth factor
      (VEGF) gene modification on skin substitute grafted on nude mice. METHODS: Human
      fibroblasts were transfected with VEGF adenovirus vector. Then the genetic
      modified fibroblasts were seeded on patches of Integra artificial skin. Twenty
      four hours later, the Integra patches were grafted onto full-thickness skin
      defects on nude mice. Seventy-two nude mice were divided into experiment (n = 18,
      E, with fibroblasts seeded on Integra which were transfected by adenovirus
      containing VEGF in advance), GFP control (n = 18, the fibroblasts were
      transfected with adenovirus containing labelled GFP segment as same as that in E
      group, but containing no VEGF gene), Fb control (n = 18, without gene
      transfection), and control (n = 18, no fibroblast was seeded on Integra) groups.
      The survival rate, the revascularization process and the histological changes in
      the grafts in gene modified group (experimental group) and control groups were
      observed and analyzed. RESULTS: The revascularization condition in the
      experimental group was much better than that in the control group. The grafts
      adhered firmly to the wound during early postoperation stage, and were more prone
      to bleed when separated from the wound. The survival rate was obviously higher,
      while the infection rate was much lower in experimental group (100.0%) compared
      with the control groups (83.3%, 75.0%, 77.8%, respectively) (P < 0.05).
      CONCLUSION: High expression of VEGF by gene modification can promote the
      vascularization process of skin substitute, hence improve the grafting result.

PMID- 15996289
TI  - [The anatomic basis and the clinical treatment of the elbow joint stiffness after
      electric injury].
AB  - OBJECTIVE: To explore the optimal method for the treatment of the elbow joint
      stiffness accompanied with neural injury after electrical injury. METHODS: Thirty
      adult cadaver elbows were fixed and dissected to observe the attachments of the
      ligaments and the muscles around the joint, and its relationship with the major
      nerves. Ten patients with electric burns with stiffness of the elbow joint were
      treated by means of loosening the anterior and posterior fascicles of radial and
      ulnar collateral ligaments, at the same time down shifting the insertion of
      flexor muscles, replacing the ulnar nerve anteriorly, in order to reconstruct
      flexor and extension functions of the elbow. The effect was evaluated with
      biomechanics criteria. RESULTS: Through anatomical study, it was revealed that
      contracture of the posterior fascicles of the radial and ulnar collateral
      ligaments and triceps brachii muscle would result in stiffness of the elbow
      joint, and contracture due to disuse of the two anterior fascicles of the radial
      and ulnar collateral ligaments and M.biceps brachii would produce flexion
      deformity of the elbow joint. Postoperatively, the functions of the elbow joints
      of all the 10 patients recovered satisfactorily. Follow-up from 1 to 3 years
      showed no change in the range of flexion and extension movements of the elbows,
      and on the contrary, mobility of the elbow joints was improved. CONCLUSION:
      Loosening of the anterior and posterior fascicles of the two collateral ligaments
      and replacement of insertions of biceps and triceps are pivotal in the treatment
      of stiffness of the elbow joint. Meanwhile lowering the origins of forearm flexor
      muscles on epicondylus and replacing anteriorly the ulnar nerve can further
      improve the flexion, function of the joint and relieve compression of the nerve.

PMID- 15996290
TI  - [Repair of rabbit tendon by autologous bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To investigate the effect of rabbit bone marrow mesenchymal stem cells
      (MSCs) as seed cells for the repair of tendon defect. METHODS: The MSCs were
      isolated, amplified and identified by detection of surface protein CD44 mRNA. A 3
      cm long defect was made in the Achilles tendon of the rabbit. The rabbits were
      divided into experimental (E) and control (C) groups. The autologous MSCs were
      implanted into a collagen-polyglycolic acid (PGA) scaffold to form a tissue
      engineered tendon, which was then transplanted to bridge the defect in the E
      group, while only collagen-PGA was transplanted to bridge the defect in the C
      group. The transplanted tendon was observed grossly and microscopically at 4, 8,
      12 weeks after operation. RESULTS: The cultured MSCs exhibited positive staining
      of CD44 on 11 days after in vitro culture. A tendon-like tissue could be
      discerned at the operation site in the E group 4 weeks after operation. Tendon
      like cells similar to normal tendon tissue, being axially arranged in collagen
      matching the mechanical direction, with uniform morphology could be seen in E
      group 12 weeks after operation. The newly regenerated tissue in C group adhered
      to the adjacent tissue and was smaller than that in E group. The collagen fibers
      in the regenerated tissue were loose with reticular and filiform structure, and
      the cells were arranged disorderly 12 weeks after the transplantation.
      CONCLUSION: It is feasible to repair the tendon defect with autologous MSCs as
      seed cells.

PMID- 15996313
TI  - [Prospect of uses of single nucleotide polymorphism in the neoplasm research ].

PMID- 15996314
TI  - [Mutation of mitochondrial 12S rRNA in gastric carcinomas and its significance].
AB  - OBJECTIVE: To detect the alterations of mitochondrial 12S rRNA in patients with
      gastric cancer, and further evaluate their effects on development of gastric
      carcinomas. METHODS: Mitochondrial 12S rRNA of 22 samples of gastric cancer
      tissues and 22 corresponding normal gastric mucosa taken from the distal portion
      of surgical specimens were PCR amplified, followed by direct DNA sequencing.
      Laser capture microdissection technique (LCM) was used to isolate cancerous cells
      and dysplastic cells from patients with specific mutations. Denaturing high
      performance liquid chromatography (DHPLC) plus allele-specific PCR (AS-PCR), nest
      PCR and polyacrylamide gel electrophoresis (PAGE) were applied to further
      evaluate this mutant property and quantitative difference of mutant type between
      cancerous and dysplastic cells. Finally, RNAdraw bio-soft was used to analyze the
      RNA secondary structure of mutant type 12S rRNA. RESULTS: Compared with mitomap
      database, some variations were firstly found, among which np652 G insertion and
      np716 T-G transversion were only found in cancers. There existed statistically
      significant difference in variant frequency of 12S rRNA between intestinal type
      and diffuse type of gastric carcinoma, 5/17 (29.4%) and 12/17 (70.6%)
      respectively (P < 0.05). DHPLC analysis showed that 12S rRNA np652 G insertion
      and np716 T-G transversion were heteroplasmic mutation. Variant frequency of 12S
      rRNA in cancer was higher than that in dysplasia (P < 0.01). 12S rRNA 652G
      insertion had more adverse effect on secondary structure stability of 12S rRNA
      than T-G transversion did. CONCLUSION: Highly variant frequency of mitochondrial
      12S rRNA may be associated with intestinal type of gastric cancer. Most parts of
      variations exist in both cancer and normal tissues and may not be characteristic
      of tumor specificity. However np652 G insertion and np716 T-G transversion may
      possess some molecular significance on gastric cancerogenesis. During the process
      of progression from normality through dysplasia to cancer, 12S rRNA tended to
      transit from homoplasmy (wild type) and heteroplasmy to homoplasmy (mutant type,
      np717 T-G).

PMID- 15996315
TI  - [The association of HeLa cell apoptosis induced by arsenic trioxide with the down
      regulation of HPV18 E6 oncogene and inhibition of telomerase activity].
AB  - OBJECTIVE: To study the effect of As2O3 induction of HeLa cell apoptosis on HPV18
      E6 expression and telomerase activity. METHODS: HeLa cells were treated with
      As2O3 in various concentrations. The effect of As2O3 on HeLa cell survival and
      apoptosis was determined by MTT assay, light and electron microscopy, and flow
      cytometry. Telomerase activity in HeLa cells was determined by TRAP-ELISA and the
      expression of HPV18 E6 mRNA was assayed by RT-PCR. RESULTS: After being treated
      with 2 micromol/L As2O3 for 48 h, the survival of HeLa cells decreased, and
      marked apoptosis was observed in a time- and dose-dependent manner. There was a
      good correlation between cell apoptosis and viral E6 gene expression and
      inhibition of telomerase activity following As2O3 treatment. CONCLUSION: The
      molecular mechanisms of As2O3 effect on HeLa cells may be related to down
      regulation of HPV18 E6 oncogene expression and inhibition of telomerase activity.

PMID- 15996316
TI  - [Experimental induction of immunity by anti-idiotypic vaccines against small-cell
      lung cancer].
AB  - OBJECTIVE: To investigate the efficacy of anti-idiotype antibody 3F6 and its
      single-chain variable fragment (3F6 ScFv) to induce humoral and cellular immune
      responses against small-cell-lung cancer (SCLC). METHODS: 3F6 and 3F6 ScFv (Ab2)
      were used to immunize BALB/c mice. The reaction of antibodies (Ab3) with specific
      antigen on NCI-H128 cells was tested by ELISA and Western blot, and the antibody
      binding inhibition assays were performed by competitive Western blot. Cellular
      immunity against SCLC induced by Ab2 was detected by a delayed-type
      hypersensitivity response and mouse lymphocyte proliferation assay. RESULTS: The
      sera immunized with Ab2 showed significant reaction (P < 0.001, as compared to
      control sera) with SCLC-specific antigen on NCI-H128 cells and specifically
      competed the binding of 2F7 (Ab1) to the specific antigen. DTH responses
      challenged with NCI-H128 cells were significantly (P < 0.001) stronger in mice
      immunized with Ab2 as compared to mice immunized with normal mouse IgG. T cell
      proliferation was significantly higher in Ab2-immunized mice (P < 0.05) than in
      control mice. CONCLUSION: The two kinds of anti-idiotypic antibodies successfully
      mimic the SCLC-specific antigen on NCI-H128 cell and induce strong humoral and
      cellular immune responses to SCLC-specific antigen in syngeneic mice. They may
      become novel vaccines against human small-cell-lung cancer and worthy of further
      investigation.

PMID- 15996317
TI  - [PTEN induces anoikis through its phosphatase activity in hepatocellular
      carcinoma cells].
AB  - OBJECTIVE: To investigate the effect and mechanisms of tumor suppressor gene PTEN
      on the induction of anoikis of hepatocellular carcinoma SMMC-7721 cells. METHODS:
      SMMC-7721 cells were transfected with GFP plasmids containing wild-type PTEN or
      phosphatase inactivating mutant PTEN (C124A-PTEN) in vitro; The PTEN expression
      and the phosphorylation levels of focal adhesion kinase (FAK) and protein kinase
      B (PKB/Akt) were detected by Western blotting; Flow cytometry assay and laser
      scanning confocal microscopy were used to analyze apoptosis in adherent and non
      adherent cells. RESULTS: Compared with the control, PTEN expression in the cells
      transfected with wild-type PTEN increased to 248%, while the phosphorylation
      level of FAK and Akt decreased 65.2% and 89.1%, respectively; and the anoikis
      percentage increased from 9.5% to 31.3%. In the cells transfected with C124A
      PTEN, neither the phosphorylation of FAK and Akt nor the anoikis percentage had
      obviously changed, although the PTEN expression enhanced dramatically in
      comparison with the control. CONCLUSION: Through its phosphatase activity, tumor
      suppressor gene PTEN can suppress the phosphorylation of FAK and Akt, and induce
      anoikis in hepatocellular carcinoma cells.

PMID- 15996318
TI  - [Expression of gastrin in human gastric cancer cell line and effect of anti
      gastrin mAb on the cell growth].
AB  - OBJECTIVE: To investigate the expression of gastrin in human gastric cancer cell
      line SGC-7901 and the effects of gastrin-17 and anti-gastrin mAb on its growth.
      METHODS: The expression of gastrin was determined by immunohistochemistry with
      anti-gastrin mAb prepared by our group. In a series of experiments, the growth of
      SGC-7901 cells was evaluated by MTT assay on cells grown in serum-free medium and
      treated with gastrin-17 and/or anti-gastrin mAb. RESULTS: Immunohistochemical
      examination of SGC-7901 cells revealed a specific gastrin immunoreactivity.
      Gastrin-17 significantly stimulated cell growth at the concentrations of 1 x 10(
      9) mol/L approximately 1 x 10(-5) mol/L in a dose-dependent manner. The growth of
      SGC-7901 cells treated with anti-gastrin mAb, either alone or in combination with
      gastrin-17 (1 x 10(-7) mol/L), was significantly inhibited. CONCLUSION: Growth of
      human gastric cancer cells SGC-7901 can be stimulated in an autocrine fashion.
      The gastrin-stimulated growth of gastric cancer cells can be blocked by anti
      gastrin mAb bound specifically with gastrin. Further study on the significance of
      anti-gastrin mAb in designing immunotherapy targeting to gastrin or gastrin
      receptor is warranted.

PMID- 15996319
TI  - [Induction of apoptosis in human hepatoma cell line SMMC7721 by Newcastle disease
      virus HN gene].
AB  - OBJECTIVE: To investigate the mechanisms of apoptosis induced in human hepatoma
      cell line SMMC7721 by plasmid pVHN constructed with Newcastle disease virus (NDV)
      HN gene. METHODS: Twenty-four h after transfection with liposome-plasmid pVHN
      complexes in vitro, the mortality rate of SMMC7721 cells was determined by MTT
      staining and flow cytometry (FCM) with PI staining. The alteration of
      mitochondrial trans-membrane potential of the cells was detected by FCM with
      rhodamine 123 staining. Cell genomic DNA was detected by agarose electrophoresis.
      The activation of caspase-3 was assayed by its substrate color reaction. RESULTS:
      Significant apoptosis was induced by transfection with plasmid pVHN into the
      cells for 24 h and the mortality rate was 50.0% (the mortality rate of control
      group was 5.2%). Genomic DNA was fragmented and mitochondrial trans-membrane
      potential was decreased, but caspase-3 activity increased. CONCLUSION:
      Significant apoptosis in SMMC7721 cells can be induced by NDV HN gene. Apoptosis
      may be resulted from the decrease of mitochondrial trans-membrane potential and
      activation of Caspase-3.

PMID- 15996320
TI  - [A comparison of human papillomavirus detection and ThinPrep cytology test for
      women in Guangdong province].
AB  - OBJECTIVE: To evaluate the etiological significance of human papillomavirus (HPV)
      in cervical cancer and the clinical utility of HPV detection in cervical cancer
      screening. METHODS: Hybrid capture II test was used to detect 13 high-risk HPV
      genotypes from cervical scrapes of 2636 women. Cervical cytology was also
      evaluated in 454 of them by ThinPrep Pap smear. RESULTS: Among 2636 women, 699
      (26.5%) were found to be high-risk HPV positive. The highest infection rate
      (59.4%) was found in the age group of < or = 20 years and the lowest infection
      rate in the age group of 41 approximately 50 years (21.0%). Significant
      differences in HPV infection rate were found between different cities in
      Guangdong province, such as those between Xinhui and Guangzhou, Xinhui and
      Shenzhen, Xinhui and Dongguan (P < 0.01). Fifteen out of 16 women (93.8%) with
      cervical carcinoma were infected with high-risk HPV versus 24 out of 125 women
      (19.2%) attending routine cervical cancer screening (P < 0.001). The HPV
      infection rate was 30.8% (142 out of 461) in women with cervical erosion, which
      was significantly lower than that in patients with cervical carcinoma (P <
      0.001). HPV DNA were detected in 100% (2/2) of squamous cell carcinoma (SCC),
      100% (12/12) high grade squamous intraepithelial lesion (HSIL), 88.9% (16/18) of
      low grade squamous intraepithelial lesion (LSIL) and 37.8% (28/74) of atypical
      squamous cells (ASC). CONCLUSION: High-risk HPV genotypes are the major causes of
      cervical cancers and HPV detection is a reliable adjuvant tool for cervical
      cancer screening.

PMID- 15996321
TI  - [Detection and clinical study of serum tumor markers in patients with colorectal
      cancer].
AB  - OBJECTIVE: To investigate the diagnostic value and clinical significance of serum
      tumor markers CEA, CA19-9 and CA242 in patients with colorectal cancer. METHODS:
      The serum levels of CEA, CA19-9 and CA242 were determined by ELISA before surgery
      in 134 patients with colorectal cancer and in 200 healthy people as a control.
      RESULTS: The CEA, CA19-9 and CA242 levels in patients were significantly higher
      than those in controls (P < 0.01, respectively). The sensitivity of CEA and CA242
      for colorectal cancer diagnosis was higher than that of CA19-9, and the combined
      sensitivity of CEA + CA242 and CEA + CA242 + CA19-9 were higher than that of
      single item or the other two combinations (CEA + CA19-9 and CA19-9 + CA242). In
      Dukes stages A, B, C and D, serum levels and sensitivity of the three tumor
      markers were significantly and successively increased. In the cases with lymph
      node metastasis, levels of the three tumor markers were significantly increased.
      The markers levels were also significantly and successively increased along with
      the extent of cancer infiltration. CONCLUSION: The results indicate that the
      combined use of CEA and CA242 or the three markers is an useful adjuvant
      diagnostic measure for colorectal cancer, and is helpful in the evaluation of
      lymph node metastasis, degree of invasion and Dukes staging in cancer treatment.

PMID- 15996322
TI  - [Expression of KAI1 gene in human laryngeal carcinoma and its clinical
      significance].
AB  - OBJECTIVE: To explore the mRNA expression of KAI1 gene in laryngeal squamous-cell
      carcinoma and its clinical significance. METHODS: Fresh laryngeal cancer samples
      taken from 40 laryngeal carcinoma cases and normal control laryngeal tissues from
      9 subjects were examined with semi-quantitative reverse transcription polymerase
      chain reaction (RT-PCR). RESULTS: Moderate, low and negative expression rates of
      KAI1 gene mRNA in nine normal laryngeal tissues were 33.3% (3/9), 33.3% (3/9) and
      33.3% (3/9), respectively. The high, moderate, low and negative expression rates
      of KAI1 mRNA in 25 laryngeal cancers without lymph node metastasis were 40.0%
      (10/25), 28.0% (7/25), 20.0% (5/25) and 12.0% (3/25), respectively. The moderate,
      low and negative expression rates of KAI1 mRNA in 15 laryngeal cancers with lymph
      node metastasis were 20.0% (3/15), 26.7% (4/15) and 53.3% (8/15), respectively.
      The KAI1 mRNA expression in the laryngeal cancers without lymph node metastasis
      was higher than that in normal laryngeal tissues (P < 0.05). The KAI1 mRNA
      expression in the laryngeal cancers with lymph node metastasis was lower than
      that in the laryngeal cancers without lymph node metastasis (P < 0.05). The high,
      moderate and low expression rates of KAI1 mRNA in 10 highly differentiated
      laryngeal cancers were 50.0% (5/10), 30.0% (3/10) and 20.0% (2/10), respectively.
      The high, moderate, low and negative expression rates of KAI1 mRNA in 12 low
      differentiation laryngeal cancers were 8.3% (1/12), 16.7% (2/12), 16.7% (2/12)
      and 58.3% (7/12), respectively. The differences of KAI1 mRNA expression between
      high and low differentiation laryngeal cancers were statistically significant (P
      < 0.05). CONCLUSION: The decrease of KAI1 mRNA expression may be related to lymph
      node metastasis and low differentiation of laryngeal squamous-cell carcinoma.

PMID- 15996323
TI  - [Expression of osteopontin mRNA and its clinical significance in gastric cancer].
AB  - OBJECTIVE: To investigate the expression of osteopontin mRNA and its correlation
      with clinicopathologic features of gastric cancer and elucidate its role in tumor
      invasion and distant metastasis. METHODS: The expression of OPN mRNA was detected
      by semi-quantitive RT-PCR. The relationship between the relative content of OPN
      mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: In
      66 cancer tissue samples, a 330 bp band was detected in 50 cases, the positive
      rate of OPN mRNA expression was 75.8% (50/66). The expression in all 20 cases of
      normal gastric mucosa was negative. The expression was associated with the depth
      of tumor invasion, diameter, lymph node metastasis and but had no correlation
      with differentiation grades. The 66 patients were followed up for 10
      approximately 27 months (mean 16 months). The OPN mRNA expression positive group
      (50 cases) had recurrence in 15 patients and the negative group (16 cases) had
      only 1 case with recurrence (P = 0.05); 10 patients died in OPN mRNA expression
      positive group but no patient died in OPN staining negative group (P = 0.05).
      CONCLUSION: OPN mRNA is over-expressed in gastric cancer. It reflects the
      progression of disease and association with poor prognosis of gastric cancer. OPN
      may play an important role in the process of distant metastasis in gastric
      cancer.

PMID- 15996324
TI  - [Thyroid clear cell carcinoma: a case report].

PMID- 15996325
TI  - [Correlation between ATP bioluminescence tumor chemosensitivity assay and
      clinical response in ovarian cancer].
AB  - OBJECTIVE: To determine the correlation between results of ATP bioluminescence
      tumor chemosensitivity assay (ATP-TCA) of human ovarian cancer specimens in vitro
      and clinical chemo-therapeutic responses of patients. METHODS: Thirty-four
      freshly taken ovarian cancer specimens (28 cases) and ascites (6 cases) and 9
      chemotherapeutic drugs were tested in vitro for cancer chemosensitivity by ATP
      TCA. RESULTS: Among the 34 ovarian cancer cases, the efficacy of ATP-TCA is
      94.0%, the sensitivity, the specificity, the positive and negative predicting
      values, and an overall predicting value in vitro and vivo were 90.0%, 91.7%,
      94.7%, 84.6% and 90.6%, respectively. CONCLUSION: The results of ATP-TCA assay
      are correlated well with clinical treatment responses. The assay may be an
      important and useful method for individual-based chemotherapy of cancers.

PMID- 15996326
TI  - [Parotid gland sebaceous adenocarcinoma: a case report].

PMID- 15996327
TI  - [The value of serum tumor marker in the diagnosis of lung cancer].
AB  - OBJECTIVE: To evaluate five serum tumor markers used alone or in combination for
      the diagnosis of lung cancer. METHODS: The level of five serum tumor markers:
      NSE, pro-GRP, CYFRA21-1, p53 antibody and CEA was detected by ELISA in 50 healthy
      adults, 170 lung cancer patients and 60 patients with respiratory infection.
      RESULTS: The level of the five serum tumor markers in lung cancer patients was
      significantly higher than that of healthy adults and patients with respiratory
      infection (P < 0.01). The level of NSE and pro-GRP in patients with small-cell
      lung cancer was significantly higher than those of the other subtypes of lung
      cancer (P < 0.01); The level of CYFRA21-1 in patients with squamous-cell
      carcinoma was significantly higher than that of other subtypes (P < 0.01). The
      specificity of p53 antibody was 100% in diagnosing lung cancer and the
      sensitivity of NSE, pro-GRP was much higher for small-cell lung cancer than for
      other subtypes (P < 0.01); The same was observed in CYFRA21-1 for the diagnosis
      of squamous-cell carcinoma (P < 0.01). The sensitivity of the tumor markers in
      diagnosing lung cancer was significantly enhanced if used in combination (P <
      0.01). CONCLUSION: These five tumor markers are valuable auxiliary parameters in
      diagnosing lung cancer. The combination of NSE and pro-GRP is more appropriate
      than other combinations in diagnosing small-cell lung cancer; the combination of
      CYFRA21-1, CEA and p53 antibody is the most valuable combination for diagnosing
      non-small-cell lung cancer. p53 antibody has the highest specificity for
      diagnosing lung cancer; CYFRA21-1 is the most valuable parameter for diagnosing
      squamous carcinoma.

PMID- 15996328
TI  - [Clinicopathological study of 4 renal juxtaglomerular cell tumors].
AB  - OBJECTIVE: To investigate the clinical characteristics, morphologic and
      immunohistochemical features, diagnosis, differential diagnosis, histogenesis and
      prognosis of renal juxtaglomerular cell tumor (JGCT). METHODS: Light microscopic
      observation; immunohistochemical assay of CK8, E-cadherin/CK7, CD10, Vim, Actin,
      CD34, S100, HMB45, CD31, Chr, Syn and CD117, EM; and follow-up were done on all 4
      surgically treated JGCT patients. RESULTS: All 4 JGCT were observed in young
      adult with clinically uncontrolled severe hypertension. Grossly, the tumor was
      encapsulated and small in size. Microscopically, the tumor cells grew in sheets
      predominantly, but papillary and onion-like pattern could also be seen. The
      stroma contained prominent vasculature that consisted of numerous thin-wall
      vessels clustering around thick-walled vessels. Tumor cells were rather small,
      polygonal, with slightly eosinophilic cytoplasm and ill-defined cell border.
      Nuclei were uniform in size but nuclear atypia and mitosis could be seen.
      Numerous mast cells were scattered among the tumor cells, and tubules were
      identified in 3 of 4 cases with positive expression of distal tubule marker of E
      cadherin/CK7. Tumor cells positively expressed Vim, Actin, calponin, and CD34.
      All cases presented ultrastructural features of distinct rhomboid-shaped crystal.
      There was no recurrence or metastasis but hypertension persisted in three during
      follow-up (mean 37 months) for all 4 JGCT patients. CONCLUSION: JGCT, originating
      from the juxtaglomerular cell, has a distinct benign entity, and it is typically
      found in young adults with severe hypertension. It has a unique morphology and
      ultrastructure features and positive immunoreactivity to Vim, Actin, calponin and
      CD34.

PMID- 15996329
TI  - [Clinicopathologic study of 24 patients with vulvar intraepithelial neoplasia
      III].
AB  - OBJECTIVE: To review the diagnosis methods and treatment modalities of vulvar
      intraepithelial neoplasia III (VINIII) and to analyse its prognostic factors.
      METHODS: The data of 24 patients with VINIII from 1992 to 2002 were
      retrospectively reviewed and analysed. RESULTS: Among these 24 patients, 62.5%
      (15 patients) were aged less than 40 years and 37.5% (9 patients) over 40 years.
      Human papillomavirus (HPV) infection was found in 53.3% and 2/9 of these two
      groups. Treatment modality for all patients was surgical excision including
      extended local excision (33.3%) and simple vulvectomy (66.7%). 3 patients (12.5%)
      developed recurrence. Positive resection margin was correlated with recurrence,
      while age, HPV infection, multifocality and resection modality were not.
      CONCLUSION: During recent years, the incidence of VIN has been on the increase in
      younger woman patients which maybe due to the increase of HPV infection, and the
      data show that the recurrence rate is correlated with positive margin. Treatment
      should be individualized and either extended local excision or simple vulvectomy
      is appropriate. Periodical follow-up should be done.

PMID- 15996330
TI  - [Correlation between magnetic resonance diffusion weighted imaging and cell
      density in astrocytoma].
AB  - OBJECTIVE: To evaluate the apparent diffusion coefficients (ADC) in magnetic
      resonance diffusion weighted imaging with echo-planar technique in depicting the
      tumor cellularity and grading of astrocytoma. METHODS: Thirty-four astrocytoma
      patients including 18 male and 16 female with age from 10 to 73 years (mean 38.4
      years) were examined by MRI and eventually proved by surgical resection and
      pathological examination. Of them, 26 had low-grade (grade I, II) astrocytoma and
      8 high-grade (grade III, IV) astrocytoma. ADC value of astrocytoma was determined
      on magnetic resonance diffusion weighted images. Cellularity of the astrocytoma
      was analyzed using Adobe Photoshop 7.0.1 software. RESULTS: The mean ADC value
      (in units of 10(-4) mm(2)/s) of the high-grade astrocytomas (7.34 +/- 2.95) was
      significantly lower than that of the low-grade astrocytomas (13.76 +/- 3.31) (t =
      4.91, P < 0.001). The mean cellularity of the high-grade astrocytomas (19.81 +/-
      9.73)% was significantly higher than that of the low-grade astrocytomas (4.74 +/-
      2.96)% (t = 4.32, P = 0.003). ADC value of the astrocytoma was significantly and
      negatively correlated with its cellularity (r = -0.535, P = 0.001). CONCLUSION:
      ADC value of astrocytoma is significantly and negatively correlated with its
      cellularity. Magnetic resonance diffusion weighted imaging may well be highly
      potential in predicting the degree of astrocytoma.

PMID- 15996331
TI  - [Prognostic value of thymidylate synthase, topoisomerase-1 and Ki-67 in advanced
      colorectal cancer patients on irinotecan and fluorouracil treatment].
AB  - OBJECTIVE: To investigate the prognostic value of thymidylate synthase (TS),
      topoisomerase-1 (Topo-1), and proliferating index Ki-67 in advanced colorectal
      cancer patients on irinotecan (CPT-11) in combination with fluorouracil treatment
      (5-Fu). METHODS: The biomarker expression of TS, Topo-1 and Ki-67 in 78 patients
      detected immunohistochemically were correlated with the clinical outcome.
      RESULTS: The expressions of those biomarkers were not correlated with clinical
      therapeutic response, but with time to progression (TTP) and/or overall survival
      (OS). Patients with low expression of TS had significantly longer TTP (P < 0.05)
      and in OS (P < 0.05). The low expression of Ki-67 was also significantly
      predictive of longer survival (P < 0.05). As compared with any biomarker, the
      combination of any two biomarkers still possessed no predictive value to
      therapeutic response, but an enhanced predictive value to prognosis. The median
      time to progression in patients with low expression of TS, or Ki-67, or both were
      9, 8 and 17 months, respectively; in patients with low expression of TS, or Topo
      1, or both were 9, 9 and 13 months; in patients with low expression of Topo-1, or
      Ki-67, or both were 8, 9 and 11 months. TTP was significantly longer in patients
      with low expression of two biomarkers as compared with those with high expression
      (P = 0.031). CONCLUSION: TS, Topo-1, and Ki-67 are not predictive for
      chemotherapy response to CPT-11 combined with 5-Fu, but valuable in predicting
      prognosis. The combination of any two biomarkers can provide more powerful
      prognostic information for advanced colorectal cancer patients.

PMID- 15996332
TI  - [Application of partial costectomy and costophrenic angle closure to supplement
      high intensity focused ultrasound treatment for liver tumor].
AB  - OBJECTIVE: To investigate the application of partial costectomy and costophrenic
      angle closure (PCCAC) and perioperative management in the treatment of liver
      tumor by high intensity focused ultrasound (HIFU). METHODS: The clinical data of
      69 patients with liver tumor underwent HIFU within the recent four years were
      retrospectively reviewed. RESULTS: 92.8% of these 69 liver tumor patients had had
      concomitant diseases and 13.0% of them developed postoperative complications
      without anyone died. There was no significant postoperative dysfunctions of
      kidney or lung as compared with the preoperative ones (P > 0.05). CONCLUSION: In
      the treatment of liver tumor by HIFU, PCCAC, as an auxillary means, giving few
      complications and little harmful effects on respiratory physiology, is highly
      safe.

PMID- 15996333
TI  - [Uses of total mesorectal excision in preservative anus operation of rectal
      cancer].

PMID- 15996334
TI  - [The evolution of the journal "Endokrynologia, Diabetologia i Choroby Przemiany
      Materii Wieku Rozwojowego" in 10 years].
AB  - BACKGROUND: In 2004 the half-yearly "Endokrynologia, Diabetologia i Choroby
      Przemiany Materii Wieku Rozwojowego" celebrated 10-years own anniversary. The
      development of the journal reflect mostly the scientific growth of narrow medical
      specialties as paediatric endocrinology. OBJECTIVES: Presentation scientific
      achievements, and the history of its origin. MATERIAL AND METHODS: In the paper
      we used materials that are at disposal of the Editor and the Publisher of the
      journal. Present its history, authors used own documentations, they were
      cooperators of this journal. CONCLUSION: Appearance of the half yearly
      "Endokrynologia, Diabetologia i Choroby Przemiany Materii Wieku Rozwojowego" was
      a very important factor in the development of pediatric endocrinology. In this
      periodical scientists can exchange scientific and clinical experience to serve
      the development of endocrinology. The journal present the main trends of the
      development of science studies, short reports and actual congress announcements.

PMID- 15996335
TI  - [Soluble thrombomodulin--a molecular marker of endothelial cell injury in
      children and adolescents with obesity].
AB  - BACKGROUND: Endothelial damage is an early step in the pathogenesis of
      atherosclerosis which begins in early childhood after exposure to atherogenic
      risk factors such as obesity. Its progression may lead to very severe
      cardiovascular complications. TM -- a specific marker of endothelial cell damage,
      is a transmembranous glycoprotein with anti-coagulant properties. It has a large,
      extracellular region comprising a thrombin binding site. TM-thrombin complex
      becomes an activator of protein C which inactivates factor Va and VIIIa and
      thereby inhibits the blood coagulation cascade. OBJECTIVES: The aim of the
      present study was to investigate if plasma concentration of sTM (one of markers
      of endothelial cells injury) is higher in children and adolescents with obesity.
      MATERIALS AND METHODS: We studied 22 obese children, 11 girls and 11 boys, (age
      range 8.5-17.8 years), and 17 normal weight healthy controls, (age range 12-17.9
      years) without family history of cardiovascular diseases. We measured plasma
      concentration of sTM, blood lipids profile, body weight and BMI. As sTM is
      excreted by the kidney we also measured plasma level of creatinine and its
      clearance. RESULTS: Plasma concentration of sTM in the group with obesity was
      significantly higher than that in the control group. There were no significant
      association between sTM and age or sex. Compared with non-obese patients, obese
      children had higher plasma concentration of total cholesterol, LDL-c,
      triglycerides, but these were not significant differences. However there was a
      significantly lower level of HDL-c in children with obesity. In addition
      statistically significant correlation between sTM and BMI was observed in the
      obese group. CONCLUSIONS: Statistically higher level of sTM in children with
      obesity compared with healthy individuals makes us sure that endothelium cells,
      even in children who were shortly exposed to atherogenic risk factors such as
      obesity, are noticeably damaged. These results constitute an additional signal
      that a lot of effort should be put into the endeavors to eliminate atherogenes
      risk factors in children population in order to prevent cardiovascular events.

PMID- 15996336
TI  - [Carbohydrate metabolism in patients with Turner syndrome. The effect of therapy
      with growth hormone, oxandrolone and a combination of both].
AB  - Insulin resistance or the impairment of insulin capability to decrease blood
      glucose levels is seen in approximately 25% of girls with Turner syndrome (TS).
      Growth hormone (hGH), especially when administered at pharmacological doses, may
      additionally negatively affect the carbohydrate metabolism in TS girls, changing
      the response of peripheral tissues to insulin. The aim of the report was the
      assessment of glucose and insulin release and the prevalence of insulin
      resistance in physiological conditions (baseline and post-standard meal values),
      as well as after oral and IV glucose tolerance test in patients with Turner
      syndrome after a 6-month therapy with growth hormone, oxandrolone (Ox) and a
      combination of these two agents (hGH+Ox). The authors also evaluated the effect
      of these three therapeutic methods on carbohydrate metabolism, attempting to
      define the risk of glucose intolerance, type 2 diabetes and hyperinsulinemia and
      insulin resistance. The analysis of individual results in all the patients
      revealed that laboratory criteria for diagnosis type 2 diabetes (glycemia at 120
      min OGTT >12.2 mmol/l) were met by one patient subjected to a combined therapy.
      Glucose intolerance (IGT) in OGTT, normally seen in 12.5% of untreated girls, was
      not intensified following a 6-month hGH or Ox therapy, but was more pronounced in
      patients on the combined treatment. A tendency was seen towards fasting
      hyperinsulinism (>25 uLI/ml) in patients on hGH and hGH+Ox, with more pronounced
      insulin resistance (IR1<7, IR2>5) in girls on the combined therapy. CONCLUSIONS:
      Combined treatment with growth hormone and oxandrolone results in a significant
      increase of insulin secretion and increased insulin resistance. In view of the
      effects of insulin resistance, one should analyze the advisability of combined
      treatment with growth hormone and oxandrolone in girls with Turner syndrome.

PMID- 15996337
TI  - [Ultrasonographic evaluation of atherosclerotic changes in carotid and brachial
      arteries in children with growth hormone deficiency before GH replacement
      therapy].
AB  - BACKGROUND: According to very well documented onset of atherosclerosis in early
      childhood, scientists are looking for good diagnostic methods for evaluating
      first changes in arterial blood vessels non-invasively. We want to know more
      about pathogenetic mechanisms and about changes in vessels especially in the
      group of young people with risk factors of premature atherosclerosis. The role of
      endothelial dysfunction in the very early phase of this process is known very
      well so far. High resolution echocardiography seems to be a good method which
      allows to examine arteries in children and adolescents. Because of localization,
      brachial and carotid arteries are a very good field for this kind of
      examinations. OBJECTIVES: Evaluation with high resolution echocardiography,
      selected parameters of endothelial function in children with growth hormone
      deficiency before replacement therapy. We measured the intimal plus medial
      thickness in carotid communis arteries (IMT) also. MATERIAL AND METHODS: We
      examined a group of 24 children (19 boys and 5 girls) aged 8-16 yr (mean 12 yr)
      suffered from growth hormone (GH) deficiency. The control group consisted of 24
      children in similar age and sex relation. Using high resolution echocardiography,
      B-mode images, we measured in end diastole, distance "m-m" in brachial arteries
      (distance between two "m" lines which are borders among media and adventitia of
      near and far wall of the artery) at rest, during reactive hyperaemia (with
      increased flow causing endothelium-dependent dilatation FMD), again at rest and
      after sublingual glyceryl trinitrate (causing endothelium-independent dilatation
      NTGMD). Using Doppler technique we evaluated baseline flow and calculated degree
      of reactive hyperemia. We also measured intimal plus medial thickness in every
      carotid artery three times and calculated mean value. In our analysis we
      estimated concentrations of cholesterol, HDL-cholesterol, LDL-cholesterol and
      triglycerides. RESULTS: In children with growth hormone deficiency the vessel
      size was smaller then in the control group and FMD was significantly impaired
      (10.05% v. 14.62%; p=0.058). NTGMD was similar to the control group (p=0.,371).
      We noticed higher IMT values in the whole examined group compared to the control
      group (0.52 mm v. 0.41 mm; p=0.0000). We noticed an important correlation between
      FMD and IMT in whole patients (examined plus control group) (p=0.004). The level
      of total cholesterol was higher in the examined group (p=0.039). CONCLUSIONS: 1.
      FMD evaluated in brachial artery, seems to be an useful sign of impaired
      endothelial function in children suffering from the risk factors of
      atherosclerosis. 2. The evaluation of IMT in carotid arteries in patients with
      growth hormone deficiency showed a more advanced degree of atherosclerotic
      changes in this group compared to healthy controls. 3. Ultrasonographic
      evaluation of premature atherosclerosis in children with growth hormone
      deficiency is a basis for the future estimation of positive effects of the
      replacement therapy.

PMID- 15996338
TI  - [Understanding health by adolescents with diabetes mellitus type 1 assessed by
      own criteria].
AB  - BACKGROUND: The word "health" has different meanings according to gender, age,
      social and health status as well as value system which points out life goals.
      OBJECTIVES: To determine the criteria of understanding "health" by adolescents
      with diabetes type 1 compared to the healthy peers. MATERIAL AND METHODS: Study
      group comprised 66 adolescents (34 girls and 32 boys) 14-18 years old (mean
      15.9+.1.3 years) suffering from diabetes mellitus for more than 2 years (mean
      4.3+/-3.4 years). Control group of 60 healthy adolescents (30 girls and 30 toys)
      was matched for age and gender. The List of Health's Criteria by Juczynski
      including 24 items of positive descriptions of physical, psychological and social
      dimensions of health was used. RESULTS: Important differences as well as some
      similarities between two groups were found. Adolescents with diabetes mellitus
      understood health in physical and psychological aspects (as proper eating habits,
      enjoying life, having efficient all parts of the body). Less important value they
      attribute to processes connected with: being responsible, solving own problems,
      controlling emotions and impulses. CONCLUSIONS: Diabetic adolescents understand
      the concept of "being healthy" in a different way than their healthy peers.
      Criteria the diabetic youngsters choose result probably from their health status
      and demonstrate the difficulties these children face while following the
      therapeutic recommendations. Problems understanding, psychological support as
      well as increased medical information about the disease may improve their quality
      of their life.

PMID- 15996339
TI  - [Lipid disturbances in type 1 diabetes mellitus--cardiovascular risk factor].
AB  - Cardiovascular diseases are the cause of the highest mortality in Poland. In
      children and adolescents with type 1 diabetes mellitus there is a significant
      increase of risk of hypertension, cardiovascular diseases and atherosclerosis
      later in life. It is important to identify risk factors early in this group.
      There is a need to undertake appropriate preventive and therapeutic measures
      already in early childhood in order to avoid these disorders.

PMID- 15996340
TI  - [Salt wasting syndrome caused by congenital, insufficient synthesis or
      aldosterone function--etiology, diagnosis and management].
AB  - Salt wasting syndrome is caused by a congenital or acquired synthesis disorder or
      by the aldosterone function disorder. It manifests itself by ionic disorders
      where the sodium and chlorine level decrease with the simultaneous potassium
      retention. Synthesised aldosterone is in the glomerular zone of the adrenal
      cortex. Symptoms of dyselectrolitemia are not distinctive, they develop within a
      few first days of life. The suction aversion, apathy, lack of growth or
      progressing, body mass loss is being noticed. The most often cause of salt
      wasting syndrome is the congenital cortical adrenal hyperplasia (CAH) caused by
      21-hydroxylase enzyme deficit. The classic form with and without salt wasting
      (SW), as well as non-classic form is distinguished. The therapy of SW form
      depends on Hydrocortisone and Cortineff administering. The other forms of salt
      wasting syndrome occur not so often and these are: aldosterone synthesis deficit,
      dehydrogenase 3beta-hydroxysteroid deficit, lipoid cortical hyperplasia, adrenal
      hypoplasia congenital (AHC), adrenoleukodystrophy and pseudohypoaldosteronism.
      The knowledge of the symptoms and causes of salt wasting syndrome allows for the
      proper therapeutic management and contributes to the regular psychophysical
      infantile development of the children.

PMID- 15996341
TI  - [Insulin resistance and hyperinsulinemia--risk factors of the metabolic syndrome
      in the pubertal population].
AB  - Pubertal insulin resistance has been well documented, the fall in insulin
      sensitivity (Sl) during puberty is associated with a compensatory increase in
      insulin secretion. Observation of pubertal insulin resistance showed that insulin
      stimulated glucose metabolism was approximately 30% lower in a sample of children
      at Tanner stages II-IV compared with children at Tanner stage I or adults.
      Although the phenomenon of pubertal insulin resistance is well documented, the
      mechanism has not been clearly determined. Pubertal insulin resistance occurs
      during a time of profound changes in body composition and hormone levels.
      Resistance of the body to the actions of insulin results in increased production
      of this hormone by the pancreas and ensuing hyperinsulinemia. Obesity beginning
      in childhood often precedes the hyperinsulinemic state. Other components of the
      insulin resistance syndrome are also present in children and adolescents.
      Conditions of insulin resistance, hyperinsulinemia, dyslipidemia, hypertension
      and obesity, especially in constellation, are potent risk factors of coronary
      atherosclerosis among adolescents and young adults. Early conservative
      intervention with diet, exercise, and behavioral therapy may prevent the
      complications of insulin resistance.

PMID- 15996342
TI  - [Complete gonadal dysgenesis 46, XY in a 16-year-old girl with a female phenotype
      -case report].
AB  - We present a case of a 16-year-old girl, who attended the Endocrinology
      Outpatient Clinic of the University Paediatric Hospital in Krakow, because of
      lack of breast development and primary amenorrhea. Pubic hair development was
      normal. Baseline hormonal blood tests indicated a primary gonadal lesion
      (hypergonadotropic hypogonadism). Ultrasonography examination revealed bilateral
      streak gonads in ovarian localisation. Uterus was present. The karyotype was
      male: 46, XY. Gonadectomy was performed due to risk of gonadoblastoma development
      in streak gonads. Based on the histology of the removed gonads the final
      diagnosis of complete gonadal dysgenesis 46, XY was established. After the
      gonadectomy hormonal replacement therapy was introduced. Authors emphasise the
      importance of considering in each case of delayed puberty in teenage girls the
      possibility of complete gonad dysgenesis 46, XY. The diagnosis can be established
      only on the support of a reliable knowledge of male sex differentiation
      physiology.

PMID- 15996343
TI  - [True hermaphroditism in a 14-year-old boy--diagnostic and therapeutic
      difficulties].
AB  - The authors present a boy with a 46, XX/46, XY karyotype in whom true
      hermaphroditism was diagnosed, stressing the importance of establishing the cause
      of the condition and further management prior to discharging the neonate. The
      ultimate sex must allow the patient to best fulfill his/her psychosocial role in
      society.

PMID- 15996344
TI  - Corticosteroids.

PMID- 15996345
TI  - Topical tacrolimus: a review of its uses in dermatology.
AB  - Tacrolimus is one of the newer immunosuppressants that act by inhibiting T-cell
      activation and cytokine release. It is approved for the treatment of atopic
      dermatitis, and its safety and efficacy have been extensively studied in large
      scale randomized controlled trials and open-label studies worldwide involving
      over 12,000 patients and up to 3 years of follow-up. Since its introduction,
      anecdotal reports and case series have found topical tacrolimus also to be
      effective and well tolerated in patients with a variety of other skin disorders,
      including other types of eczema, papulosquamous disorders, disorders of
      cornification, rosacea, other inflammatory skin conditions, vesiculobullous
      diseases, vitiligo, connective-tissue diseases, graft-versus-host disease, and
      follicular disorders. This paper reviews the currently available evidence on the
      use of topical tacrolimus for these conditions, as well as its safety profile and
      cost-effectiveness. Tacrolimus does appear to offer a safe and efficacious
      alternative that minimizes the need for topical glucocorticoids and does not
      cause skin atrophy. However, the risk of systemic absorption is increased with
      generalized disruption of the skin barrier. Further large-scale studies are
      needed to clarify the efficacy of topical tacrolimus in a variety of conditions
      for which anecdotal reports of success exist, especially in regard to different
      racial groups and in comparison to (as well as in combination with) other
      existing therapies. Long-term safety data should continue to be monitored and
      reported.

PMID- 15996346
TI  - A topical cream containing a zinc gel (allergy guard) as a prophylactic against
      latex glove-related contact dermatitis.
AB  - BACKGROUND: Many health care workers are sensitized to the proteins in natural
      rubber latex and get contact dermatitis as a result of wearing latex gloves.
      OBJECTIVE: The aim of the study was to evaluate a topical formulation containing
      a zinc gel (Allergy Guard) as a prophylactic against latex glove-related contact
      dermatitis. METHODS: The study was carried out with volunteers who exhibited mild
      to moderate contact dermatitis (type IV) after wearing latex gloves as per the
      protocol. RESULTS: Allergy Guard significantly reduced skin irritation in
      volunteers who exhibited type IV hypersensitivity when exposed to latex gloves.
      Allergy Guard also exhibited a barrier effect as shown by the permeation of
      chlorophyllin dye into the skin of volunteers. Allergy Guard prevented dermal
      irritation induced by sodium lauryl sulfate. CONCLUSION: Topical formulations
      containing a zinc gel may be used to delay or prevent latex sensitivity,
      especially among health care professionals.

PMID- 15996347
TI  - Contact dermatitis in hairdressers, 10 years later: patch-test results in 300
      hairdressers (1994 to 2003) and comparison with previous study.
AB  - BACKGROUND: In the last 20 years, the hairdressing profession has undergone
      important modifications, mainly because of a change in the substances and
      techniques used and improved occupational education. OBJECTIVE: To evaluate the
      modifications in the hairdressing profession and its actual risk of occupational
      allergic contact dermatitis (OACD). METHODS: We studied all 300 hairdressers seen
      in our department from 1994 to 2003 and compared the results with those of a
      previous study of 379 hairdressers who attended our department from 1980 to 1993.
      All were patch-tested with the European Standard series and specific hairdressing
      products. As previously, most of the workers were women (93%), with a mean age
      (23.7 years) slightly higher than that of the workers in our previous study.
      RESULTS: We found a significant increase in the frequency of positive patch-test
      responses (78.3% vs 58.8%) and OACD (58% vs 48.8%) with respect to our previous
      study. We also observed a significant increase in sensitization to most
      allergens, including p-phenylenediamine base (54% vs 45.9%), 4-aminobenzene
      (40.7% vs 31.9%), ammonium thioglycolate (2.7% to 12.3%), ammonium persulfate
      (7.9% to 14.3%), p-toluenediamine sulfate (6.8% to 15.3%), p-aminodiphenylamine
      (2.9% to 7.7%), o-nitro-4-phenylenediamine (2.1% to 7.3%), and aminophenols (0%
      to 9%), whereas a decrease was found in sensitization to Disperse Orange (17% vs
      32.7%) and thioglycolic acid (15.3% to 3%). CONCLUSION: The high frequency and
      increase of sensitizations among hairdressers require urgent measures to improve
      protective measures and their application.

PMID- 15996348
TI  - Allergic contact dermatitis from cyanamide.
AB  - Cyanamide (carbimide or calcium carbimide) has been used to treat chronic
      alcoholism for more than 45 years. The skin reactions provoked by this medication
      are very rare and are generally associated with systemic reactions after
      ingestion of the product. However, allergic contact dermatitis has also been
      detected on persons who prepare cyanamide for administration to patients. We
      present a case of work-related allergic contact dermatitis from cyanamide that
      was confirmed by patch testing.

PMID- 15996349
TI  - Granuloma annulare presenting as contact dermatitis.
AB  - Granuloma annulare is a benign idiopathic disorder of the dermis that has various
      clinical presentations and an unknown etiology. We discuss a patient who
      presented with a contact dermatitis that demonstrated granuloma annulare on
      biopsy. The most likely etiologic agent was a substance known as FAZ (an exhaust
      product of Kodak DryView laser imaging film), to which the patient was exposed in
      his occupation.

PMID- 15996350
TI  - The painful purple digit: an alarming complication of Candida albicans antigen
      treatment of recalcitrant warts.
AB  - Candida albicans (CA) antigen immunotherapy for recalcitrant warts is a novel
      treatment that has had much success in the recent past. Although several side
      effects are well documented in the literature, we report a new adverse reaction
      to CA antigen immunotherapy for verruca vulgaris of the distal fingertip. Our
      patient received an intradermal injection of CA antigen solution into periungual
      warts located on the distal left thumb and distal subungual area of the left
      index finger. Within 24 hours, the patient reported pain, edema, and a purple hue
      to only the index finger. Incision of the finger demonstrated no hematoma or
      compartment syndrome. Although the etiology is unknown, we believe the condition
      was most likely due to edema and vascular compromise secondary to a vigorous
      delayed-type hypersensitivity reaction, possibly leading to cyanosis of the
      distal index finger. We report this case to make physicians who use intralesional
      CA antigen aware of a new possible complication at this anatomic location.

PMID- 15996351
TI  - Lyral: a fragrance allergen.
AB  - Fragrances are a common cause of contact dermatitis and account for a large
      percentage of reactions to cosmetic products. Novel fragrance compounds that may
      not be detected by the common fragrance screening agents (including balsam of
      Peru and fragrance mix) are continually being produced. Lyral is one of those
      allergens found in many cosmetic and household products. This review will discuss
      the recent literature and the significance of this allergen to allergic contact
      dermatitis.

PMID- 15996352
TI  - Influence of platelet-rich plasma added to xenogeneic bone grafts in periimplant
      defects: a vital fluorescence study in dogs.
AB  - BACKGROUND: The use of platelet-rich plasma (PRP) has been suggested in order to
      increase the rate of bone deposition when sites are augmented prior to or in
      conjunction with dental implant placement. PURPOSE: The goal of this study was to
      investigate whether the addition of PRP to xenogeneic bone grafts would increase
      the rate of bone formation in dogs. MATERIALS AND METHODS: Ninety endosseous
      dental implants were inserted in the mandibles of nine hound dogs. Subsequently,
      mesial and distal three-wall periimplant defects were surgically created. Defects
      were randomly assigned to three groups: demineralized freeze-dried bone graft
      plus platelet-rich plasma (DFDBG plus PRP), demineralized freeze-dried bone graft
      alone (DFDBG), and no treatment. Postsurgically each dog received a series of
      three fluorescent labels for estimation of bone cell activity at baseline and
      during different stages of healing, with particular attention to the bone
      formation rate per tissue volume (BFR/TV). Animals were sacrificed at 1 month, 2
      months, and 3 months, and specimens were subjected to analysis by fluorescence
      microscopy. Treatment effects were evaluated with analysis of variance models.
      RESULTS: Overall, the average BFR/TV differed by treatment although this
      difference approached only minimal statistical significance (p = .057). The
      largest difference occurred between periimplant defects treated with DFDBG only
      and defects that were not treated (mean percentage BFR/TV, 0.0720% vs 0.0994%).
      There was no evidence of an overall treatment effect (p = .27) for the mineral
      apposition rate (MAR) values. The data also suggest a consistent variability in
      the bone formation parameters among the three groups at different healing points.
      CONCLUSION: In this animal model the addition of PRP to xenogeneic bone grafts
      did not demonstrate evidence of faster bone formation during healing. However,
      limitations of the histologic technique possibly played a negative role in the
      assessment of bone formation parameters.

PMID- 15996353
TI  - Radiographic analysis of the transcrestal sinus floor elevation: short-term
      observations.
AB  - BACKGROUND: There are some limitations for implant placement in the posterior
      maxilla when there is an extended sinus. Various techniques for sinus floor
      elevation allow an increase in implant length. PURPOSE: The aim of the present
      radiographic study was to assess the augmented site in the sinus around implants
      that were installed by means of an osteotome-mediated transcrestal sinus floor
      elevation. MATERIALS AND METHODS: Thirty-three patients with 44 implants were
      available. In 39% of the implants the sinus floor elevation was performed
      exclusively with bone chips. Bone fill material (Bio-Oss, Geistlich Sohne AG,
      Wolhusen, Switzerland) was additionally used to increase the volume and stability
      of the lifted area at 61% of the implants. The visibility and morphology of the
      augmentation were assessed and compared by means of intraoral radiography (long
      cone technique). RESULTS: All implants were stable and were considered to be
      successful when they were reexamined in the context of the present study. The
      mean residual bone height was 5.78 +/- 1.4 mm. The increase of the implant length
      as compared to the original bone height resulted in a mean value of 3.87 +/- 2.0
      mm. The volume and density of the lifted area were more visible if Bio-Oss was
      added. A shrinkage and/or condensation of the grafted material was visible at 37%
      of the implants after a minimum loaded period of 200 days. Equally, a decreased
      visibility of the original sinus floor was noted at 61% of implants. The
      formation of a cortical bone layer at the apex of the implants was detected at
      35% of implants. CONCLUSIONS: The surgical procedure appears to be a safe method
      with rare complications. Radiographic assessment of the augmentation procedure
      proved to be difficult, and measurements are not fully reliable.

PMID- 15996354
TI  - Bone graft and implants in a patient with systemic mastocytosis.
AB  - BACKGROUND: Systemic mastocytosis (mast-cell proliferation in various organs,
      including the skeleton) is a rare disease. Reports on mastocytosis that affects
      facial bones are few. The bone lesions may be osteolytic or sclerotic. PURPOSE:
      To describe (for the first time) bone grafting followed by dental implant
      treatment yielding a good result in a patient with systemic mastocytosis.
      MATERIALS AND METHODS: A bone graft was performed on a 60-year-old woman with
      systemic mastocytosis. Dental implant treatment was performed 13 weeks after
      sclerotic bone of the iliac crest was grafted to the maxillary sinus bilaterally.
      A microimplant was installed simultaneously with the dental implants and was
      removed 6 months later for histomorphometric evaluation. Bone biopsy specimens
      from the donor site of the sclerotic iliac crest and later from the remodeled
      maxillary bone graft were histologically analyzed. A clinical examination of the
      patient with regard to her mastocytosis was performed by a dermatologist. The
      patient was followed up after 3 years. RESULTS: Bone grafting and dental implant
      treatment were successful, and the patient's clinical and radiologic situation
      was stable after 3 years. Histologic examination of the bone grafted from the
      iliac crest showed sclerotic lesions in the bone and a dense infiltration of mast
      cells. The bone graft seemed to remodel initially in a normal way in the
      maxillary sinus. However, computed tomography 3 years later showed regions of
      sclerosis in the remodeled maxillary bone. These lesions now had a pattern
      similar to the adjacent facial bone. Both the microimplant and the dental
      implants integrated well. Bone-implant contact measured on the microimplants was
      20% higher in this actual case, compared to that of patients previously treated
      and grafted with the same technique. CONCLUSIONS: There are many clinical
      implications to be considered when treating this group of patients. Bone
      grafting, remodeling of the bone, and dental implant installation were successful
      in this patient with systemic mastocytosis and signs of osteosclerosis.
      Installation of microimplants in patients with pathologic bone conditions may
      allow successful dental implant treatment.

PMID- 15996355
TI  - Validation of microfocus computed tomography in the evaluation of bone implant
      specimens.
AB  - BACKGROUND: Microfocus computed tomography (muCT) is an emerging technique owing
      to its speed, full three-dimensional information, and nondestructive properties.
      PURPOSE: The aim of this study was to explore the efficacy of a muCT system
      (Philips HOMX 161, Philips Medical Systems GmbH, Hamburg, Germany) for
      visualization of the bone structure around screw-type titanium implants by
      comparing muCT images with their histologic homologues. MATERIALS AND METHODS:
      Eight screw-type titanium implants were placed in the femoral condyles of two
      goats. After the excised implant-bone specimens were embedded in resin, three
      dimensional muCT of the excised implant and bone specimens was performed.
      Histologic sections were subsequently made. A total of 150 histologic sections
      were matched with muCT images. RESULTS: Bone trabeculae were clearly visible on
      the muCT scans. However, bone close to the implant or present in the apical
      surface features of the implant could not be detected. The overall matching
      between muCT scans (slices) and the histologic sections was 89%. CONCLUSION:
      Investigation of trabecular bone around titanium implants by muCT can be
      considered highly reliable for determining trabecular bone parameters, with the
      exception of measuring direct bone-to-implant contact.

PMID- 15996356
TI  - Simplified methods of implant treatment in the edentulous lower jaw: a 3-year
      follow-up report of a controlled prospective study of one-stage versus two-stage
      surgery and early loading.
AB  - BACKGROUND: Interest in the use of one-stage surgery and immediate loading of
      oral implants has lately been increasing. PURPOSE: The aim of this study was to
      compare the 3-year results of one-stage surgery versus two-stage surgery, early
      loading versus loading after a 3-month healing period, and the use of one-piece
      implants versus the use of two-piece implants. MATERIALS AND METHODS: The study
      included 108 patients with edentulous mandibles. Each patient was treated with
      four Branemark System implants (Nobel Biocare AB, Goteborg, Sweden) and with full
      fixed prostheses. Patients were consecutively treated and were distributed in
      four groups: group A (one-stage surgery), group B (control group with two-stage
      surgery), group C (one-piece implants), and group D (early loading). In groups A
      and B Branemark Standard implants and standard abutments were used. In group C
      the conical one-piece Branemark implant was used, and in group D the patients had
      Branemark System Mk III implants together with multiunit abutments. All patients
      were observed for 3 years. RESULTS: Of the 432 inserted implants, 24 were lost.
      Survival rates in the three experimental groups ranged from 93.2 to 93.3% whereas
      the survival rate in group B (the control group with two-stage surgery) was
      97.5%. The differences between the groups were not statistically significant. The
      changes in marginal bone level were measured from fixture insertion to the final
      follow-up at 3 years. The bone loss in group D (early loading) was significantly
      less than in group B (the control group) whereas there were no differences in
      marginal bone change between the other groups. CONCLUSIONS: Early loading seemed
      to give good results in the anterior part of the mandible. The survival rate of
      the early-loaded implants did not significantly differ from that of implants
      inserted with the conventional two-stage procedure, but the mean marginal bone
      loss around the surviving implants was less with early loading.

PMID- 15996357
TI  - An antibacterial surface on dental implants, based on the photocatalytic
      bactericidal effect.
AB  - BACKGROUND: It is well known that the moderately roughened surfaces of dental
      implants enhance direct bone-implant contact. However, rough implant surfaces, as
      compared to smooth surfaces, are thought to pose a higher risk of bacterial
      infection when exposed to the oral cavity. PURPOSE: This study was focused on
      evaluating the photocatalytic bactericidal effects of anatase titanium dioxide
      (TiO(2)) on gram-negative anaerobic bacteria known to be associated with
      periimplantitis. MATERIALS AND METHODS: A film of photocatalytic anatase TiO(2)
      was added onto the surface of commercially pure titanium disks by plasma source
      ion implantation (PSII) followed by annealing. The photocatalytic properties of
      the film were confirmed by the degradation of methylene blue. Actinobacillus
      actinomycetemcomitans and Fusobacterium nucleatum cells were incubated
      anaerobically and seeded on the disk. The disks were then exposed to ultraviolet
      A (UVA) illumination from black light in an anaerobic environment. After
      illumination, the number of viable cells was counted in terms of colony-forming
      units. RESULTS: The anatase TiO(2) film added by the PSII method and annealing
      exhibited a strong photocatalytic reaction under UVA illumination. The viability
      of both types of bacteria on the photocatalytic TiO(2) film was suppressed to
      less than 1% under UVA illumination within 120 minutes. CONCLUSION: The
      bactericidal effect of the TiO(2) photocatalyst is of great use for sterilizing
      the contaminated surface of dental implants.

PMID- 15996358
TI  - Tissue engineering with recombinant human bone morphogenetic protein-2 for
      alveolar augmentation and oral implant osseointegration: experimental
      observations and clinical perspectives.
AB  - Surgical placement of oral implants is governed by the prosthetic design and by
      the morphology and quality of the alveolar bone. Nevertheless implant placement
      often appears difficult, if at all possible, due to aberrations of the alveolar
      ridge. Hence prosthetically dictated implant positioning often entails
      augmentation of the alveolar ridge and adjoining structures. In this review we
      discuss recent observations of the biologic potential, clinical relevance, and
      perspectives of application of recombinant human bone morphogenetic protein-2
      (rhBMP-2) technologies for alveolar bone augmentation and oral implant
      osseointegration. Using discriminating critical-size supraalveolar defects and
      clinical modeling in dogs, we show that rhBMP-2 has a substantial potential for
      augmenting alveolar bone and supporting osseointegration of titanium oral
      implants. Moreover, using clinical modeling, we demonstrate re-osseointegration
      in advanced periimplantitis defects and long-term functional loading of titanium
      oral implants placed into rhBMP-2-induced bone. Our studies suggest that
      inclusion of rhBMP-2 for alveolar bone augmentation and oral implant fixation
      will not only enhance the predictability of existing clinical protocol but also
      allow new approaches to these procedures.

PMID- 15996359
TI  - Canine or chameleon (revisited): a never-ending challenge in a perpetually
      changing world.

PMID- 15996360
TI  - Why does organized medicine in the United States continue to fail the public
      interest? A European's concern.

PMID- 15996361
TI  - Total laparoscopic aortofemoral bypass as a routine procedure for the treatment
      of aortoiliac occlusive disease.
AB  - The purpose of our study was to evaluate whether total laparoscopic aortofemoral
      bypass can be performed routinely in patients who require surgical intervention
      for aortoiliac occlusive disease. In a prospective study, 68 consecutive patients
      underwent total laparoscopic aortofemoral bypass between 2002 and 2004. Among
      these patients, there were 50 men and 18 women, with a mean age of 68.4 +/- 9
      years. The mean operating time was 199 minutes, with a mean aortic cross-clamp
      time of 85.8 minutes. There were five major complications (7.3%). The mean
      postoperative hospital stay was 6.3 days. Most of the younger patients could be
      discharged on the third or fourth postoperative day. Our results show that total
      laparoscopic aortic surgery can be offered as a routine procedure to the majority
      of patients with long-segment aortoiliac occlusive disease.

PMID- 15996362
TI  - Upper limb ischemia: 20 years experience from a single center.
AB  - The objective of this study was to review a single center's experience of upper
      limb revascularization over 20 years. All patients undergoing operative or
      endovascular upper limb revascularization between June 1983 and July 2003 were
      identified. One hundred eighty-four upper limb revascularization procedures were
      carried out on 172 patients. Sixty-one patients had a thromboembolic event (35%),
      53 patients presented with a traumatic vascular injury (31%), and 29 patients had
      symptoms of chronic atherosclerotic upper limb ischemia (17%). Fifteen patients
      had subclavian steal syndrome, eight patients had thoracic outlet compression,
      and six patients had iatrogenic injuries of the upper limb arteries. Fifty-five
      thromboembolectomies were performed, 37 under locoregional anesthesia. Ten
      patients (18.2%) died from cardiopulmonary causes following embolectomy. Fifteen
      reversed saphenous vein bypass grafts were performed for traumatic damage. Twenty
      seven patients had a primary repair, and five required a vein patch. One patient
      subsequently had an arm amputation, and two patients died. Twelve patients
      presenting with chronic arm ischemia had a subclavian angioplasty, 12 patients
      had a proximal bypass, and in 5 patients, stenoses were stented. The mortality in
      this group was 6.9% (2 of 29). The mortality for upper limb revascularization was
      8.7%. Almost all deaths occurred after upper limb embolectomy, and the mortality
      of this procedure was similar to that of lower limb embolectomy. Deaths were the
      result of cardiac comorbidity, and this should be actively sought and treated if
      outcomes are to improve.

PMID- 15996363
TI  - Selection of treatment for patients with carotid artery disease: medication,
      carotid endarterectomy, or carotid artery stenting.
AB  - Patients presenting with atherosclerosis of the extracranial carotid arteries may
      be offered carotid endarterectomy (CEA), carotid artery stenting (CAS), or
      medical therapy to reduce their risk of stroke. In many cases, the choice between
      treatment modalities remains controversial. An algorithm based on patients'
      neurologic symptoms, comorbidities, limiting factors for CAS and CEA, and
      personal preferences was developed to determine the optimal treatment in each
      case. This algorithm was then employed to determine therapy in 308 consecutive
      patients presenting to a single institution during one calendar year. Ninety-five
      (30.8%) patients presented with an asymptomatic carotid stenosis of more than 80%
      and 213 (69.2%) with a symptomatic stenosis of more than 50%. According to our
      algorithm, 59 (62.1%) of the 95 asymptomatic patients received CAS, 20 (21.1%)
      received CEA, and 16 (16.8%) received medical therapy. All symptomatic patients
      underwent intervention; 153 (71.8%) were treated with CAS and 60 (28.2%) with
      CEA. Combined 30-day stroke and death rates after CAS were 1.7% in asymptomatic
      patients and 2.6% in symptomatic patients. After CEA, these rates were 0% and
      3.3%, respectively. Careful selection of treatment modality according to
      predetermined criteria can result in improved outcomes.

PMID- 15996364
TI  - Experimental force measurements on a bifurcated endoluminal stent graft model:
      comparison with theory.
AB  - The goal of this study was to experimentally validate a steady-state mathematical
      model, which can be used to compute the forces acting on a bifurcated endoluminal
      stent graft. To accomplish this task, an acrylic model of a bifurcated graft was
      used for the force measurements. The graft model was connected to the inlet
      piping with a flexible rubber membrane that allowed the graft model to move. This
      allowed us to measure the force owing to the movement of the graft model with a
      calibrated load cell. Steady-state blood flow was assumed, and the working fluid
      was water. The experimental data were found to be consistent with the results
      from a previously published mathematical model: the graft force is strongly
      dependent on the proximal or inlet pressure and the inlet area. The force tends
      to be weakly dependent on flow rate. More research work will be required to
      determine whether the steady-state force model examined in this article provides
      a realistic determination of the forces on an endoluminal stent graft that is
      subject to pulsatile blood flow.

PMID- 15996365
TI  - Does specialization improve outcome in abdominal aortic aneurysm surgery?
AB  - Specialization and high volume are reported to be related to a better outcome
      after abdominal aortic aneurysm repair. The aim of this study was to compare, in
      patients undergoing abdominal aortic aneurysm repair, the outcomes of those whose
      surgery was done by general surgeons with the outcomes of those whose surgery was
      done by specialist vascular surgeons. All patients undergoing abdominal aortic
      aneurysm repair at the Basel University Hospital (referral center) from January
      1990 to December 2000 were included. Patients with endovascular treatment were
      excluded. Operations in group A (n = 189), between January 1990 and May 1995,
      were done by general surgeons. Operations in group B (n = 291), between June 1995
      and December 2000, were done by vascular surgeons. In-hospital mortality and
      local and systemic complications were assessed. In-hospital mortality rates were
      significantly lower for group B (with specialist surgeons) than for group A, both
      overall (group B, 11.7%; group A, 21.7%; p = .003) and for emergency
      interventions (group B, 28.1%; group A, 41.9%; p = .042). The reduction in
      mortality for elective surgery in group B was not statistically significant
      (group B, 1.1%; group A, 4.9%; p = .054). There were significantly fewer
      pulmonary complications in group B compared with group A (p = .000). We conclude
      that in patients undergoing abdominal aortic aneurysm repair, those whose surgery
      is done by a specialized team have a significantly better outcome than those
      whose surgery is done by general surgeons.

PMID- 15996366
TI  - Arterial reconstruction after mangled extremity: injury severity scoring systems
      are not predictive of limb salvage.
AB  - The Vascular Unit at Suez Canal University Hospital in Egypt covers a wide area
      with high rates of severe injuries. This is a prospective study of mangled
      extremities to identify risk factors associated with limb loss in these patients.
      Between December 2000 and August 2003, a prospective study on all patients with
      arterial injuries in mangled extremities was undertaken. All patients were scored
      using the Mangled Extremity Severity Score (MESS) and the Mangled Extremity
      Severity Index (MESI). During this period, arterial reconstruction was performed
      in 62 patients. Primary patency, secondary patency, and limb salvage rates were
      81%, 85.5%, and 93.5%, respectively. The only factor affecting limb salvage
      (statistical trend) was the site of trauma (upper limb 100% vs lower limb 89%; p
      = .08%). There was no significant effect related to the mechanism of trauma
      (blunt 90% vs stab 100%; p = .125), MESS (< 7, 100% vs > 7, 91%; p = .22), and
      MESI (< 20, 100% vs > 20, 90.5%; p = .154). Upper limb injuries were the least
      likely to lead to amputation. We recommend that all injuries, whatever their
      score, should be surgically explored before treatment decisions are made.

PMID- 15996367
TI  - Approach to fragmented central venous catheters.
AB  - Prolonged venous access devices are needed in cancer patients for central venous
      access. Catheter fragmentation leading to catheter malfunction represents a rare
      problem. Herein we present our experience in the management of fragmented
      catheters. Between 2001 and 2003, 183 catheters were placed via the subclavian
      vein, and five cases of fragmented catheters were observed. Fragments were
      removed by an Amplatz gooseneck snare (Microvena, St. Paul, MN) with angiographic
      intervention. The diagnosis of the breakage was made by chest radiography. The
      incidence of catheter breakage was 2.7%. All fragments were removed by the snare,
      without any complications. Catheter narrowing and breakage owing to its medial
      positioning in the subclavian vein were the main causes of catheter malfunction.
      In any case of catheter malfunction, radiologic evaluation of the catheter must
      be done to rule out its rupture. Removal of the fragments using the Amplatz snare
      is a safe and easily applied procedure.

PMID- 15996368
TI  - Combined endovascular and surgical approach (hybrid treatment) for management of
      type IV thoracoabdominal aneurysm.
AB  - The purpose of this article is to report successful hybrid treatment of a
      sovraprosthetis type IV thoracoabdominal aneurysm. This technique was used in a
      65-year-old man with chronic rupture of a type IV thoracoabdominal aneurysm not
      suitable for aortic cross-clamping because of a severe cardiopathy (left
      ventricular ejection fraction 20%); the patient underwent previous repairs of
      aortic arch and infrarenal abdominal aortic aneurysms. Perioperative
      complications were absent. Postoperative day 21 computed tomography and monthly
      duplex ultrasonography confirmed the complete exclusion of the aneurysm with
      proper perfusion of visceral vessels. At the seventh postoperative month, the
      patient died of a massive recurrence of myocardial infarction. Hybrid treatment
      for thoracoabdominal aneurysms may represent a valid solution for those patients
      with poor cardiac and respiratory reserve, reducing cardiac stress and the
      duration of visceral ischemia, which are still the main causes of morbidity and
      mortality for this type of intervention.

PMID- 15996369
TI  - The International Society for Vascular Surgery and its importance to vascular
      surgery.

PMID- 15996370
TI  - Clinical outcome and technical considerations of late removal of abdominal aortic
      endografts: 8-year single-center experience.
AB  - During an 8-year period, 355 patients underwent endovascular repair of mainly
      true (97%) infrarenal aneurysms. After a mean follow-up of 48 months, 11 (3.1%)
      patients required conversion to open repair and 10 were eligible for open
      surgical intervention. Via a midline incision, explantation of the endograft was
      performed by using an infrarenal aortotomy. Explantation was done for rupture in
      four patients (40%), with a marked difference in mortality rates between acute
      (50%) and elective (0%) explantations. The main reason for explantation was
      proximal type I endoleak caused by (1) malposition of the device, (2) proximal
      migration of the endograft, and (3) dislodgment of a tube endograft that followed
      former central reconstruction. Proximal migration is most worrisome and demands
      preventive endovascular reintervention. The mortality and morbidity rates of
      elective explantation are acceptable. When delayed conversion is indicated,
      priority has to be given to operate on these patients.

PMID- 15996371
TI  - Civil and war peripheral arterial trauma: review of risk factors associated with
      limb loss.
AB  - We sought to analyze the early results of civil and war peripheral arterial
      injury treatment and to identify risk factors associated with limb loss. Between
      1992 and 2001, data collected retrospectively and prospectively on 413 patients
      with 448 peripheral arterial injuries were analyzed. Of these, there were 140
      patients with war injuries and 273 patients with civil injuries. The mechanism of
      injury was gunshot in 40%, blunt injury in 24%, explosive trauma in 20.3%, and
      stabbing in 15.7% of the cases. The most frequently injured vessels were the
      femoral arteries (37.3%), followed by the popliteal (27.8%), axillary and
      brachial (23.5%), and crural arteries (6.5%). Associated injuries, which included
      bone, nerve, and remote injuries affecting the head, chest, or abdomen, were
      present in 60.8% of the cases. Surgery was carried out on all patients, with a
      limb salvage rate of 89.1% and a survival rate of 97.3%. In spite of a rising
      trend in peripheral arterial injuries, our total and delayed amputation rates
      remained stable. On statistical analysis, significant risk factors for amputation
      were found to be failed revascularization, associated injuries, secondary
      operation, explosive injury, war injury (p < .01) and arterial contusion with
      consecutive thrombosis, popliteal artery injury, and late surgery (p < .05).
      Peripheral arterial injuries, if inadequately treated, carry a high amputation
      rate. Explosive injuries are the most likely to lead to amputations, whereas stab
      injuries are the least likely to do so. The most significant independent risk
      factor for limb loss was failed revascularization.

PMID- 15996372
TI  - Endovascular repair of the descending thoracic aorta: evidence for the change in
      clinical practice.
AB  - The purpose was to review outcome data following endovascular repair of the
      descending thoracic aorta from reports published between 1994 and 2004. To
      accomplish this task, 1,518 patients underwent endovascular repair for thoracic
      aortic disease; 810 thoracic aortic aneurysms, 500 type B thoracic aortic
      dissections, and 106 traumatic ruptures. The 30-day mortality rate was 5.5% and
      6% for late postoperative deaths. The primary technical success rate was 97%,
      with only 15 patients requiring open conversion. Neurologic deficits occurred in
      29 patients. In total, 118 endoleaks were reported; 29 were restented, and the
      remainder required surgical intervention. Graft infection occurred in 6 cases,
      and migrations were detected in 10. The conclusion reached is that endovascular
      repair of descending thoracic aortic disease is feasible and can be achieved with
      low rates of perioperative morbidity and mortality. As few long-term data exist
      on the durability of thoracic stent grafts, lifelong surveillance remains
      necessary.

PMID- 15996373
TI  - Redefining the role of arterial imaging in the management of penetrating zone 3
      neck injuries.
AB  - The purpose of this study was to assess the role of arteriography (AG) in the
      diagnosis and treatment of vascular trauma in patients with zone 3 penetrating
      neck injuries. The records of all cases of penetrating neck trauma for the past
      14 years at a level 1 trauma center were reviewed retrospectively. Eight hundred
      forty-four penetrating neck injuries were documented, of which 72 (8.5%)
      traversed zone 3 of the neck (gunshot, 35; stab, 32; shotgun, 5). Twenty patients
      (27%) had hard signs of vascular injury (hemorrhage, expanding hematoma, bruit,
      thrill, neurologic deficit). Twelve of these (60%) underwent immediate
      exploration, 1 had no significant injury, and 11 had successful surgical repair
      or ligation of the vascular injury. AG in the other eight patients with hard
      signs revealed injuries requiring embolization (three patients), urokinase
      infusion (one patient), and observation (three patients) and one normal
      examination. Fifty-two patients had no hard signs of vascular injury. Twenty-four
      of these underwent AG, of which 18 were negative. Positive findings included
      internal carotid artery narrowings (two patients), external compression of the
      internal carotid artery (one patient), vertebral artery intimal flap (one
      patient), and nonbleeding injuries to small, noncritical arteries (two patients),
      none of which required treatment. Twenty-four of the remaining 28 patients were
      observed clinically, and 4 patients had negative explorations. Nine patients had
      ultrasonography performed, but these examinations did not yield any useful
      information. The absence of hard signs reliably excludes surgically significant
      vascular injuries in penetrating zone 3 neck trauma, suggesting that AG is not
      necessary. Hard signs in stable patients should mandate AG because these vascular
      injuries may be amenable to endovascular therapy.

PMID- 15996374
TI  - Screening algorithm for aortoiliac occlusive disease using duplex ultrasonography
      acquired velocity spectra from the distal external iliac artery.
AB  - Aortoiliac duplex scanning can be difficult to perform owing to the deep location
      of these vessels. We propose a new method to indirectly screen for aortoiliac
      disease by performing duplex examination of the distal external iliac artery
      (DEIA). After performing a preliminary study on 21 patients, the parameters of
      the Doppler waveform that best distinguish normal from diseased arteries were the
      presence or absence of reverse flow, peak systolic velocity, and resistance
      index. These values were used in a derived equation, with the value Y > or = 0.78
      predicting normal proximal inflow. We then studied 118 aortoiliac segments in 81
      consecutive patients with arteriography and DEIA duplex ultrasonography. To
      predict moderate to severe stenosis, duplex ultrasonography had a sensitivity of
      95.7%, a specificity of 84.1%, a positive predictive value of 80%, and a negative
      predictive value of 96.8%. Our formula thus predicted significant disease in 55
      of the 118 aortoiliac segments (47%), with these segments needing further
      arteriographic evaluation. The other 63 limbs can be safely considered as having
      normal aortoiliac inflow. Our method accurately screens for aortoiliac disease
      and is excellent for predicting normal inflow. This information can be used to
      better plan the intraoperative diagnostic study and intervention.

PMID- 15996375
TI  - Carotid artery imaging in the United kingdom: a postal questionnaire of current
      practice.
AB  - There has been a steady rise in the use of carotid duplex imaging in the
      selection of patients for carotid endarterectomy (CEA). Some would suggest that
      CEA could be safely performed without preoperative contrast angiography. The
      purpose of this study was to focus on the role of duplex imaging among vascular
      surgeons in the United Kingdom and to highlight current practices in imaging
      prior to CEA. A postal questionnaire was sent to all consultant members of the
      Vascular Surgical Society of Great Britain and Ireland about the choice of
      imaging prior to selection of patients for CEA, preoperative imaging, and choice
      of imaging (if any) in the confirmation of carotid occlusion indicated by duplex
      scanning. Of 396 questionnaires sent, 323 (82%) were returned. Of these, 259
      (80%) consultants performed carotid surgery, 118 (45%) in university hospitals
      (UHs) and 141 (53%) in district general hospitals (DGHs). One hundred eighteen
      (100%) and 137 (97%) respondents, respectively, chose duplex scanning as their
      first-line investigation. Sixty (51%) respondents in UHs and 49 (35%) respondents
      in DGHs repeated duplex scanning immediately preoperatively, with 57 (95%) and 46
      (94%), respectively, using duplex scanning. Forty-seven (40%) respondents in UHs
      and 78 (55%) respondents in DGHs would reconfirm an occlusion, with 30 (64%) and
      48 (62%), respectively, using computed tomography and magnetic resonance imaging
      as their preferred tool. Our study shows that duplex scanning is the first-line
      imaging technique for patient selection for CEA by vascular surgeons in the
      United Kingdom. Magnetic resonance imaging and computed tomography are replacing
      conventional angiography where duplex scanning is equivocal.

PMID- 15996376
TI  - Fulminant development of mega-aorta due to Takayasu's arteritis: case report and
      review of the literature.
AB  - Takayasu's arteritis is a rare inflammatory arteriopathy characterized by
      segmental involvement of the aorta, its major branches, and, occasionally, the
      pulmonary arteries. Arterial inflammation generally results in occlusion, but
      Takayasu's arteritis occasionally presents as aneurysm formation. Takayasu's
      arteritis generally afflicts young women and is most often characterized by an
      acute episode of systemic illness and neurologic symptoms secondary to stenoses
      of the carotid and vertebral circulation. We report an unusual case of Takayasu's
      arteritis in a 43-year-old man who presented with severe back pain and provide a
      brief review of the literature.

PMID- 15996377
TI  - Surgical repair of bilateral profunda femoris artery aneurysms.
AB  - True aneurysms of the profunda femoral artery are a rare arteriopathy. Few cases
      have been described in the literature. They are prone to spontaneous rupture and
      carry significant morbidity, including loss of limb. In light of this, elective
      repair of profunda femoris aneurysms at the time of detection is the preferred
      course of action. Surgical repair should include reconstruction of the profunda
      circulation, in addition to exclusion of the aneurysm to prevent distal ischemia.
      In this report, we describe the case of a gentleman in whom bilateral profunda
      femoris artery aneurysms were detected during angiography to investigate his
      intermittent claudication. Surgical repair involved both exclusion of the
      aneurysms and bilateral vascular reconstruction.

PMID- 15996378
TI  - Surveillance and conservative management of a persistent sciatic artery aneurysm.
AB  - A persistent sciatic artery aneurysm is a rare congenital vascular anomaly.
      Surgical intervention is reserved for symptomatic cases. The authors report the
      case of a 72-year-old woman who presented with thromboembolic occlusion of an
      aneurysmal persistent sciatic artery. Although initially symptomatic, she was
      managed expectantly with the aid of serial duplex sonographic imaging. The
      persistent sciatic artery subsequently thrombosed as a result of hypotension
      secondary to a myocardial infarction. No surgical intervention was required. The
      current literature on this condition is reviewed.

PMID- 15996381
TI  - Implant or root canal therapy: an endodontist's view.

PMID- 15996382
TI  - Metal-free dentistry.

PMID- 15996383
TI  - Immediate dentin sealing: a fundamental procedure for indirect bonded
      restorations.
AB  - The purpose of this article is to review evidence-based principles that could
      help optimize dentin bonding for indirect composite and porcelain restorations.
      More than 30 articles were reviewed, most of them addressing the specific
      situation of dentin bonding for indirect restorations. It appears that the
      combined results of this data plus clinical experience suggest the need for a
      revision in the dentin bonding procedure. Immediate application and
      polymerization of the dentin bonding agent to the freshly cut dentin, prior to
      impression taking, is recommended. This new application procedure, the so-called
      immediate dentin sealing (IDS), appears to achieve improved bond strength, fewer
      gap formations, decreased bacterial leakage, and reduced dentin sensitivity. The
      use of filled adhesive resins (low elastic modulus liner) facilitates the
      clinical and technical aspects of IDS. This rational approach to adhesion also
      has a positive influence on tooth structure preservation, patient comfort, and
      long-term survival of indirect bonded restorations. CLINICAL SIGNIFICANCE: Tooth
      preparation for indirect bonded restorations (eg, composite/ceramic inlays,
      onlays, and veneers) can generate significant dentin exposures. It is recommended
      to seal these freshly cut dentin surfaces with a dentin bonding agent (DBA)
      immediately following tooth preparation, before taking impression. A three-step
      total-etch DBA with a filled adhesive resin is recommended for this specific
      purpose. The major advantages, as well as the technical challenges of this
      procedure, are presented in detail.

PMID- 15996385
TI  - New surgical approach for root coverage of localized gingival recession with
      acellular dermal matrix: a 12-month comparative clinical study.
AB  - BACKGROUND: Acellular dermal matrix graft (ADMG) has been used as an advantageous
      substitute for autogenous subepithelial connective tissue graft (SCTG). However,
      the surgical techniques used were primarily developed for the SCTG, and they may
      not be adequate for ADMG since it has a different healing process than SCTG owing
      to its different vascular and cellular structures. This study compared the 1-year
      clinical outcome of a new surgical approach with the outcome of a conventional
      procedure for the treatment of localized gingival recessions, both performed
      using the ADMG. MATERIALS AND METHODS: The clinical parameters-probing depth,
      relative clinical attachment level, gingival recession (GR), and width of
      keratinized tissue-of 32 bilateral Miller Class I or II gingival recessions were
      assessed at baseline and 12 months postoperatively. RESULTS: Significant clinical
      changes for both surgical techniques were achieved after this period, including
      GR reduction from 3.4 mm presurgery to 1.2 mm at 1 year for the conventional
      technique and from 3.9 mm presurgery to 0.7 mm at 1 year for the new technique.
      The percentage of root coverage was 62.3% and 82.5% for the conventional and new
      techniques, respectively. Comparisons between the groups after this period by
      Mann-Whitney rank sum test revealed statistically significant greater reduction
      of GR favoring the new procedure (p = .000). CLINICAL SIGNIFICANCE: Based on the
      results of this study, it can be concluded that a new surgical technique using an
      ADMG is more suitable for root coverage when compared with the conventional
      technique. The results revealed a statistically significant improvement in
      clinical performance with the ADMG approach.

PMID- 15996387
TI  - Microtensile bond strength of luting materials to coronal and root dentin.
AB  - PURPOSE: The purpose of this study was to evaluate the microtensile bond strength
      (muTBS) of two dual-cured resin cements and a glass ionomer cement to coronal
      dentin versus root dentin. MATERIALS AND METHODS: RelyX Unicem (3M ESPE, St.
      Paul, MN, USA) and Panavia F (Kuraray Medical Inc., Tokyo, Japan) were the resin
      cements used and FujiCEM (GC Corp., Tokyo, Japan) was the glass ionomer cement
      used. Once separated, the labial coronal and root surfaces of six bovine incisors
      were ground with 600-grit SiC papers to expose middle dentin. Then, the dentin
      surfaces were treated following the manufacturers' instructions and a 1 mm thick
      layer of each material was applied to the flattened coronal and root surfaces.
      Each material was cured following the manufacturers' recommendations and a
      composite buildup was made over the cured luting materials for testing purposes.
      After 24 hours in water at 37 degrees C, the teeth were sectioned into 1 mm x 1
      mm x 6 mm beams and tested for muTBS. The data were analyzed by one- and two-way
      analysis of variance and Fisher's Protected Least Squares Differences test (p <
      .05). RESULTS: The microTBSs to coronal and root dentin were similar within each
      cement. Comparing the materials, RelyX Unicem presented the highest muTBS,
      followed by Panavia F and FujiCEM, respectively (p < .0001). CONCLUSIONS:
      Although there were differences in muTBS among the materials tested, no
      significant differences were found between bond strengths to coronal and root
      substrates. CLINICAL SIGNIFICANCE: Since bond strengths of luting materials to
      coronal and root dentin showed comparable results, there is no need to treat
      those surfaces differently prior to luting of indirect restorations.
      Nevertheless, because significant differences existed among the different luting
      materials, the choice of a luting material should be based on the type of
      preparation and restoration as well as the need for fluoride release.

PMID- 15996389
TI  - In vitro toothbrush-dentifrice abrasion of two restorative composites.
AB  - BACKGROUND: Surface wear can be a problem with directly placed composites.
      PURPOSE: This study evaluated the in vitro wear and surface roughness of two
      composites at different cycle intervals after being subjected to toothbrush
      dentifrice abrasion. MATERIALS AND METHODS: Twenty specimens of a microhybrid,
      Filtek Z250 (3M ESPE, St. Paul, MN, USA), and a nanofill composite, Filtek
      Supreme (3M ESPE), were prepared according to the manufacturer's directions. Each
      specimen was subjected to toothbrush-dentifrice abrasion (250 g vertical load)
      using a deionized water-dentifrice slurry (Close-Up, Lever Ponds Ltd., La Lucia,
      ZA) and toothbrush heads (Oral-B 40, Oral-B Laboratories, Delmont, CA, USA). A
      brushing sequence of 10,000, 20,000, 50,000, and 100,000 strokes was performed
      for all samples at a rate of 1.5 Hz. At baseline and each cycle interval, a
      surface profilometer was used to determine average surface roughness, Ra. At the
      same intervals, vertical loss of material was measured with a precision
      micrometer. Data were analyzed using repeated-measures analysis of variance at p
      value .05. Analyses with atomic force microscopy (AFM) and scanning electron
      microscopy (SEM) were also performed. RESULTS: After 20,000, 50,000, and 100,000
      cycles, Filtek Supreme showed less significant wear than Z250. Filtek Supreme
      demonstrated higher surface roughness than Z250 after 50,000 and 100,000 cycles.
      However, AFM and SEM images indicated a more uniform surface topography for
      Filtek Supreme than for Z250. Abrasion wear and surface roughness increased with
      each cycle interval for both materials. CONCLUSIONS: Although the initial
      performance of both materials was similar, a greater number of brushing cycles
      revealed differences between the wear resistance and generated surface roughness
      of the materials. CLINICAL SIGNIFICANCE: The wear resistance and roughness
      results of Filtek Supreme suggest that it is suitable for clinical use, mainly in
      areas that are more subject to abrasive wear, such as Class V restorations.

PMID- 15996391
TI  - Bright and white: is it always right?

PMID- 15996392
TI  - Adhesive-composite incompatibility, part II.
AB  - Apart from some questions related to the repairability of resin composite
      restorations, dentists have always assumed that methacrylate-based resins are
      compatible with each other. For example, there is no clinically relevant problem
      in using a microfilled composite to laminate a Class IV restoration made with a
      hybrid composite, even if they are not of the same brand or manufacturer. In the
      context of adhesive systems, we have always believed that resin composites,
      regardless of their type or composition, bond well to all types of bonding
      agents. However, unexpected debonding of self-cured, core buildup composites that
      had been bonded with single-bottle adhesive systems was reported about 5 years
      ago. Subsequent studies demonstrated that there were, indeed, compatibility
      problems between simplified adhesive systems and self- or dual-cured resin
      composites. Apparently, when such combinations are used, reduced bond strengths
      and subsequent failures at the resin-adhesive interface can occur because of
      adverse reactions between the acidic resin monomers, an integral part of the
      simplified adhesive systems, and the chemicals involved in the polymerization
      mechanism of the self- or dual-cured composites, particularly the basic tertiary
      amines.

PMID- 15996393
TI  - Gingival recession.

PMID- 15996394
TI  - Profile of pediatric hemiparesis.
AB  - Our objective was to determine the clinical spectrum of pediatric hemiparesis by
      identifying the relative frequency of various diagnoses and comorbid conditions
      seen in these children. Case records of all patients with hemiparesis in a single
      practice over an 11-year period were reviewed with reference to clinical
      features, etiologic determination, and comorbid conditions. Ninety-two children
      were identified: 73 (79.3%) had a congenital hemiparesis and 19 (20.7%) had an
      acquired hemiparesis. An abnormal perinatal history (P = .003), prematurity (P =
      .016), and younger age at onset of symptoms (P < .001) were associated with a
      congenital hemiparesis. The overall etiologic yield was 83.7% (82.2% in the
      congenital and 89.5% in the acquired). The top four etiologic entities were
      cerebrovascular ischemia (40.2%), periventricular leukomalacia (18.5%),
      intracranial hemorrhage (16.3%), and cerebral dysgenesis (13%). Factors
      predictive of establishing an underlying etiology included birth prior to 34
      weeks' gestation (P = .034), global developmental delay (P = .048), epilepsy (P =
      .024), and having appropriate imaging modalities (P = .001). Half of these
      children had a concurrent global developmental delay, associated epilepsy (odds
      ratio 3.67; 95% confidence interval 1.40-9.72), and prematurity (odds ratio 5.41;
      95% confidence interval 1.56-18.80). A third of these children developed
      epilepsy. Multivariate predictive factors for epilepsy included global
      developmental delay (odds ratio 4.20; 95% confidence interval 1.44-12.27),
      cerebrovascular ischemia (odds ratio 5.10; 95% confidence interval 1.76-14.77),
      and term birth (odds ratio 3.87; 95% confidence interval 1.20-12.56). The
      majority of children with hemiparesis have a congenital etiology. The diagnostic
      yield is higher than previously reported; however, specific underlying etiologies
      need to be better determined. Comorbid conditions of global developmental delay
      and epilepsy have a high prevalence in this population, contributing to overall
      morbidity.

PMID- 15996395
TI  - Status epilepticus: clinical analysis of a treatment protocol based on midazolam
      and phenytoin.
AB  - The efficacy of a combination of midazolam and phenytoin in treating generalized
      convulsive status epilepticus in children was studied retrospectively. The
      patient group comprised all patients admitted for generalized convulsive status
      epilepticus to the pediatric intensive care unit over 7 years. Patients treated
      according to the protocol were included (N = 122). These patients were treated
      with the following regimen; each subsequent step was taken if clinical evidence
      of epileptic activity persisted: midazolam 0.5 mg/kg rectally or 0.1 mg/kg
      intravenously. After 10 minutes: midazolam 0.1 mg/kg intravenously. After 10
      minutes: phenytoin 20 mg/kg intravenously in 20 minutes. After phenytoin load:
      midazolam 0.2 mg/kg intravenously followed by midazolam 0.1 mg/kg/hour
      continuously, increased by 0.1 mg/kg/hour every 10 minutes to maximum 1
      mg/kg/hour. Phenobarbital 20 mg/kg intravenously or pentobarbital 2 to 5 mg/kg
      intravenous load, 1 to 2 mg/kg/hour continuously intravenously. Patients who
      received initial rectal diazepam were included. Patients were categorized
      according to the cause of generalized convulsive status epilepticus. These
      categories were then related to the level of antiepileptic therapy needed.
      Patients' ages ranged from 0.5 to 197.4 months. The cause of generalized
      convulsive status epilepticus was idiopathic or febrile convulsions in two thirds
      of cases. Most (89%) patients were managed on midazolam and phenytoin.
      Generalized convulsive status epilepticus was terminated with midazolam alone in
      58 patients, with the addition of phenytoin in 19 patients and with continuous
      midazolam in 32 patients. Thirteen patients needed additional barbiturates. The
      relationship between the level of antiepileptic therapy and etiology was not
      significant. Fifty-two patients needed artificial ventilation. Seven patients
      died; no deaths were directly attributable to generalized convulsive status
      epilepticus itself. With the use of the proposed protocol, combining midazolam
      and phenytoin, 89% of the cases of generalized convulsive status epilepticus
      could be successfully managed.

PMID- 15996396
TI  - Clinical significance of tics and attention-deficit hyperactivity disorder (ADHD)
      in children with pervasive developmental disorder.
AB  - The goal of this study was to examine the clinical significance of co-occurring
      tics and attention-deficit hyperactivity disorder (ADHD) as indicators of a more
      complex symptomatology in children with and without pervasive developmental
      disorder. Parents and teachers completed a Diagnostic and Statistical Manual of
      Mental Disorders-IV-referenced rating scale for 3- to 5- (n = 182/135) and 6- to
      12- (n = 301/191) year-old children with pervasive developmental disorder and
      clinic controls, respectively. The percentage of children with tic behaviors
      varied with age: preschoolers (25%, 44%) versus elementary schoolchildren (60%,
      66%) (parent and teacher ratings, respectively). For many psychiatric symptoms,
      screening prevalence rates were highest for the ADHD + tics group and lowest for
      the group with symptoms of neither, but the pattern of group differences varied
      by age group and informant. In general, there were few differences between the
      ADHD only and tics only groups. The pattern of ADHD/tic group differences was
      similar for both children with and without pervasive developmental disorder. We
      concluded that these findings support the notion that the co-occurrence of ADHD
      and tics is an indicator of a more complex psychiatric symptomatology in children
      with pervasive developmental disorder.

PMID- 15996397
TI  - Reaching movements in childhood dystonia contain signal-dependent noise.
AB  - When reaching, children with dystonia exhibit movements that are slower and more
      variable than normal children. We hypothesize that in dystonia there is an
      increase in signal-dependent noise so that there is increased variability with
      increasing speed. This hypothesis predicts that slower movement in children with
      dystonia is at least partly due to a compensatory strategy to reduce variability
      by decreasing speed. To test this hypothesis, we measured the speed of arm
      movement while children attempted to contact buttons of different sizes. We
      tested 23 control children and 15 children between the ages of 4 and 16 years
      with dystonia owing to either cerebral palsy, idiopathic dystonia not due to the
      DYT1 (torsin A) mutation, or other identified causes. A consistent inverse
      relationship between movement time and button size was seen for both the control
      children and the children with dystonia. The variance of movement speed increased
      with the average speed for all subjects. Children with dystonia moved
      significantly more slowly at all button sizes, and their movement speed was more
      sensitive to changes in button size. Therefore, part of the reduction in speed in
      dystonia is due to relatively greater difficulty in contacting small targets.
      This finding is consistent with the hypothesis of increased signal-dependent
      noise in children with dystonia, and we present a simple computational model that
      provides a possible explanation for the origin of this noise.

PMID- 15996398
TI  - Methylphenidate in children with attention-deficit hyperactivity disorder (ADHD):
      experience from a Sri Lankan Tertiary Children's Hospital.
AB  - The response to methylphenidate was assessed in children diagnosed as having
      attention-deficit hyperactivity disorder (ADHD) in 2000 at the Lady Ridgeway
      Tertiary Hospital for Children in Sri Lanka. They were managed in outpatient
      child psychiatry clinics. ADHD was diagnosed according to the criteria of the
      Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). The severity
      of the symptoms was determined with a validated Sinhala assessment form based on
      DSM-IV criteria. The data on problems experienced by the diagnosed children and
      their families were obtained using an interviewer-administered questionnaire. The
      severity of the symptoms and problems experienced by the children and their
      families were reassessed at 6 weeks and 6 months of methylphenidate therapy.
      Thirty-seven new subjects were diagnosed as having ADHD in 2000, and 36 of them
      were treated with methylphenidate. The severity of the symptoms and the number of
      subjects receiving frequent complaints from school were significantly lower 6
      weeks after methylphenidate treatment. At 6 months of treatment, the severity of
      the symptoms was not significantly reduced when compared with the severity
      assessed 6 weeks after treatment. Methylphenidate did help with school-related
      problems in the short term, but the long-term effects of methylphenidate were not
      convincing in this group of subjects and showed poor long-term compliance,
      probably owing to inadequate improvement seen in symptoms.

PMID- 15996399
TI  - Neurologic, neuropsychologic, and electroencephalographic findings after European
      tick-borne encephalitis in children.
AB  - Tick-borne European early summer meningoencephalitis is believed to be a benign
      disease in childhood. The causative RNA virus is from the same family as the West
      Nile virus, and the respective clinical presentations have many similarities. We
      studied 19 German children who had suffered from tick-borne encephalitis virus
      meningitis or meningoencephalitis in an endemic area and compared them with 19
      matched controls. Epidemiologic data were consistent with known features of tick
      borne encephalitis infection in southern Germany. None of the children studied
      had severe neurologic or neuropsychologic sequelae. One child developed
      significant clinical depression shortly after the illness. Electroencephalograms
      (EEGs) from children with tick-borne encephalitis were significantly slower on
      follow-up than control EEGs. After tick-borne encephalitis, children had a higher
      likelihood of having an impairment of attention and psychomotor speed. Using the
      Touwen neurologic examination, after tick-borne encephalitis, children had lower
      scores than control children on 4 of the 10 subsystems. Owing to the small sample
      size, it was difficult to identify risk factors for and predictors of adverse
      outcomes.

PMID- 15996400
TI  - Genetic risk factors associated with thrombosis in children with congenital
      neurologic disorders.
AB  - Thromboembolic events during the perinatal period are responsible for
      irreversible brain damage owing to cerebral hypoxia and neuronal necrosis. We
      investigated the presence of thrombophilia risk factors in children with
      congenital neurologic disorders. Nineteen children (9 males and 10 females), aged
      1 to 14 years (median 4.5 years), who had presented with symptoms and signs of
      congenital neurologic disorders were studied. Thirty-five age-matched healthy
      children recruited from the same geographic area served as controls. Three
      patients of 19 (15.8%) were carrying the factor V Leiden mutation compared with 2
      children among the controls (5.7%). One patient was heterozygous for the
      prothrombin G20210A variant (5.2%) compared with one child who was heterozygous
      among the controls. Three patients were homozygous (15.8%) and 11 were
      heterozygous (57.9%) for the C677T 5,10-methylenetetrahydrofolate reductase gene
      mutation compared with 4 (11.5%) and 18 (51.4%), respectively, among the
      controls. Three patients of 19 (15.8%) were carrying more than one mutation. We
      found 18 mutations in 79% (15/19) of the patients and 25 mutations in 69% (24/35)
      of the healthy children. Among the individuals carrying the homozygous 677TT 5,10
      methylenetetrahydrofolate reductase genotype, we found 7 mutations in 32% (6/19)
      of the patients and 7 mutations in 20% (7/35) of the healthy children (P > .05).
      In one patient, lupus anticoagulant and antiphospholipid antibodies of IgG
      isotype were detected. Reduced activities of protein C, protein S, or
      antithrombin III were not observed in either the patient or the control group.
      Although, among our cases, we found some well-known risk factors associated with
      thrombosis in adults, the pathogenesis of these clinical entities remains
      obscure.

PMID- 15996401
TI  - Early alteration in bone metabolism in epileptic children receiving carbamazepine
      monotherapy owing to the induction of hepatic drug-metabolizing enzymes.
AB  - The purpose of this study was to investigate, by a prospective, self-controlled
      method, whether early treatment with carbamazepine monotherapy can alter bone
      metabolism in ambulatory epileptic children with adequate sun exposure, based on
      the determination of total serum alkaline phosphatase and its bone isoenzyme
      activities. Serum total alkaline phosphatase and its bone, liver, and intestinal
      isoenzyme activities were evaluated in 22 epileptic ambulatory children (13 males
      and 9 females, aged from 5 to 12 years) before and at 3, 6, and 12 months of
      carbamazepine monotherapy. Serum concentrations of other biochemical markers of
      bone and liver metabolism, such as calcium, phosphorus, magnesium, gamma
      glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and
      lactate dehydrogenase, were also measured in the study participants before and at
      6 and 12 months of treatment. Carbamazepine was prescribed at normal dosages
      (16.4-20 mg/kg/day). Serum total alkaline phosphatase activities were
      significantly increased at 3 (P = .000), 6 (P = .024), and 12 (P = .037) months
      of treatment; serum bone alkaline phosphatase activities at 3 (P = .000), 6 (P =
      .008), and 12 (P = .017) months of treatment; and serum liver alkaline
      phosphatase activities at 3 (P = .000), 6 (P = .049), and 12 (P = .008) months of
      treatment, whereas serum intestinal alkaline phosphatase isoenzyme activity was
      significantly increased only at 3 months of treatment (P = .035). Serum gamma
      glutamyltransferase activities were also significantly increased at 6 (P = .000)
      and 12 (P = .000) months of treatment. No significant changes in the
      concentrations of serum calcium, phosphorus, magnesium, alanine aminotransferase,
      aspartate aminotransferase, and lactate dehydrogenase were noted at 6 and 12
      months of treatment. There was a significant correlation between serum gamma
      glutamyltransferase activities and serum total alkaline phosphatase activities (r
      = .689, P = .000 at 6 months; r = .493, P = .020 at 12 months), bone alkaline
      phosphatase activities (r = .700, P = .000 at 6 months; r = .466, P = .029 at 12
      months), and liver alkaline phosphatase activities (r = .427, P = .047 at 6
      months; r = .425, P = .048 at 12 months). These findings indicate that ambulatory
      children who receive carbamazepine monotherapy, even when residing in a country
      with adequate sunlight, can have their bone metabolism altered early in the
      course of treatment, as indicated by the elevated activities of serum bone
      alkaline phosphatase isoenzyme. This early alteration in bone metabolism is
      probably due to the hepatic enzyme-inducing character of carbamazepine.

PMID- 15996402
TI  - Proton spectroscopic findings in children with epilepsy owing to tuberous
      sclerosis complex.
AB  - Tuberous sclerosis complex is an autosomal dominant disorder that often causes
      refractory seizures. The presence of multiple lesions makes it difficult to
      identify a single lesion responsible for the epilepsy. Our purpose is to assess
      the single-voxel proton spectroscopic findings of the tubers in 11 children with
      tuberous sclerosis complex. Prior to age 4 years, all of the patients had
      presented with epileptic seizures and multiple bilateral tubers in magnetic
      resonance images. Single-voxel proton spectroscopy was performed from the tubers
      especially showing epileptogenic activity using both the long and short echo time
      and in 14 controls. The results were analyzed using the Mann-Whitney U-test.
      Compared with the control group, the spectroscopic findings of tubers were
      characterized by decreased N-acetylaspartate to creatine ratios (1.43 +/- 0.33; P
      < .001) in both the long and short echo time spectra, increased choline to
      creatine ratios (0.91 +/- 0.082; P < .05), and myo-inositol to creatine ratios
      (0.97 +/- 0.19; P < .01) in the short echo time spectra. A lactate peak was
      detected in the regions corresponding to an epileptic focus on
      electroencephalography in six patients. Single-voxel proton spectroscopy could be
      a useful noninvasive method to evaluate epileptogenic tubers.

PMID- 15996403
TI  - Familial cognitive impairment with ataxia with oculomotor apraxia.
AB  - Ataxia with oculomotor apraxia is an autosomal recessive inherited disease
      characterized by childhood onset of progressive cerebellar ataxia, oculomotor
      apraxia, and progressive motor peripheral neuropathy. The mean age at onset is
      approximately 4.7 years, with oculomotor apraxia appearing a few years later.
      Diagnosis is based on molecular genetic analysis for mutations of the aprataxin
      (APTX) gene (chromosome 9p13.1; ataxia with oculomotor apraxia 1). Ataxia with
      oculomotor apraxia 2 is caused by an unknown gene mutation at locus 9q34. We
      describe two siblings, born to consanguineous parents, who had clinical features
      of cerebellar ataxia, tremor, dysarthria, oculomotor apraxia, and motor
      peripheral neuropathy. Brain magnetic resonance imaging showed cerebellar atrophy
      and mild brainstem atrophy. Electromyography showed signs of axonal neuropathy.
      The molecular genetic analysis demonstrated the APTX mutation W279X at locus
      9p13.3 (ataxia with oculomotor apraxia 1 disease), and psychologic studies showed
      mild cognitive impairment. We suggest that mentation can be compromised in ataxia
      with oculomotor apraxia 1.

PMID- 15996404
TI  - Not a new leukodystrophy but congenital cytomegalovirus infection.
AB  - We report a 16-month-old girl who presented with global developmental delay and
      hearing loss. Cranial magnetic resonance imaging demonstrated a pattern that
      could be interpreted as a "new leukoencephalopathy." Etiologic investigations
      revealed a positive polymerase chain reaction for cytomegalovirus DNA using her
      stored Guthrie card, indicating a congenital cytomegalovirus infection.

PMID- 15996405
TI  - Acute necrotizing encephalopathy in caucasian children: two cases and review of
      the literature.
AB  - Acute necrotizing encephalopathy is a fulminant neurologic disease seen
      predominantly in Japan and Taiwan. We present two cases diagnosed at a Canadian
      center within the same year in Caucasian children. Both were previously well,
      developed an acute viral illness with fever and vomiting, and progressed to brain
      death within 2 to 4 days. Neuroimaging and postmortem examination demonstrated
      the unique features of bilateral and severe necrosis of deep gray- and
      subcortical white-matter structures. The first case was associated with
      extensive, but transient, hepatic involvement, recent varicella and rotavirus
      infections, and detailed metabolic studies, including mitochondrial functional
      analysis, were normal. The second case tested positive for influenza A infection,
      whereas evidence of liver damage was lacking. Both children demonstrated early
      lymphopenia and myocardial necrosis, two features not previously associated with
      acute necrotizing encephalopathy. These cases are unique in their occurrence in
      non-Japanese children and are among the first published reports in Canada.

PMID- 15996406
TI  - Two cases of glycine encephalopathy accompanied by pes equinovarus.
AB  - Glycine encephalopathy is a rare autosomal recessive metabolic disease
      characterized by glycine accumulation in body fluids owing to a defect in the
      glycine cleavage system. There are several forms of glycine encephalopathy. In
      the classic or neonatal form, symptoms usually develop as neurologic symptoms in
      the first few days of life. It characteristically presents with hypotonia,
      lethargy, apnea, and seizures and usually results in death by 1 year of age. In
      this report, we present two cases of neonatal glycine encephalopathy accompanied
      by isolated pes equinovarus deformity.

PMID- 15996407
TI  - Benign familial infantile convulsions: phenotypic variability in a family.
AB  - Benign familial infantile convulsion is an autosomal dominant epilepsy syndrome
      characterized by seizures starting from 3 to 12 months and a favorable outcome.
      We present a Turkish family with benign familial infantile convulsions and report
      the clinical variability associated with this syndrome in three generations. All
      11 affected members had benign infantile seizures, which were primarily
      generalized in all but one patient, who had partial seizures with secondary
      generalization. The seizures started within the first year and were accompanied
      by normal neurologic development and a good response to treatment with
      phenobarbital. In this family, the phenotype extended beyond infancy. The index
      patient had unilateral occipital spike and waves on electroencephalography (EEG),
      although he had no clinical seizures at 4 years of age. Follow-up EEG of this
      patient 1 year later showed that the discharges shifted to the occipital lobe of
      the other hemisphere. The grandmother of this patient had temporal lobe seizures
      as an adult, years after the remission of infantile convulsions. One of the
      patients experienced paroxysmal choreoathetosis during adolesence. Our findings
      highlight the intrafamilial phenotypic variability of benign familial infantile
      convulsions in a large pedigree with long-term follow-up.

PMID- 15996409
TI  - Objective evaluation of skin pressure distribution of graduated elastic
      compression stockings.
AB  - BACKGROUND: The beneficial effects of graduated elastic compression stockings
      (GCSs) have been demonstrated. However, their pressure performances are variable
      and unstable in practical applications owing to many influencing factors.
      Comprehensive assessment of skin pressure profiles may help elucidate the
      mechanisms of action of compression stockings. OBJECTIVE: The objective of this
      study was to quantify and objectively evaluate the magnitude and distribution of
      skin pressure applied by different GCSs and to analyze the possible reasons
      influencing the stocking pressure performances. METHODS: Six healthy females were
      required to wear eight kinds of GCSs with different pressure levels while
      standing upright. The skin pressures of 16 different positions located in four
      heights and four directions of the lower limb were measured and recorded by
      FlexiForce interface pressure sensors (Tekscan, Inc., Boston, MA, USA) and a
      multichannel measuring system. RESULTS: The pressure gradients, pressure levels,
      and testing locations significantly influenced skin pressure (p < .001). All
      tested GCSs exerted the highest pressure at the ankle region, and the pressure
      gradually decreased toward the thigh, which follows the gradient design of GCSs.
      However, many of them failed to produce the perfect pressure gradients from the
      ankle region to the calf region. Obviously, reversed pressure gradients occurred
      in the medial side of the leg, where the pressure at the ankle region was lower
      than that on the prominent part of the calf by 36% on average. GCSs with higher
      pressure levels applied higher skin pressure on the lower limb. The pressure at
      the anterior side was far higher than that in the medial and lateral directions.
      The distribution patterns of skin pressure at transverse sections were similar to
      the anatomic outlines of cross sections of the leg. The measured average ankle
      pressure of all tested GCSs did not reach the pressures specified by the
      manufacturers. CONCLUSION: Skin pressure distributions and magnitudes applied by
      GCSs were significantly influenced by the locations of testing points in terms of
      height and direction, which are determined by the specific anatomic structure and
      body shape of individual human legs and potentially influenced by the pressure
      sensor and testing methods.

PMID- 15996410
TI  - The static stiffness index: a simple method to assess the elastic property of
      compression material in vivo.
AB  - BACKGROUND: The efficacy of compression therapy depends mainly on the exerted
      pressure and on the stiffness of the material. OBJECTIVE: To propose a simple
      method by which pressure and stiffness can be assessed in the individual patient.
      MATERIAL AND METHODS: Using a pressure transducer (Kikuhime small probe,
      MediTrade, Soro, Denmark) the sub-bandage pressure is measured on the medial
      aspect of the lower leg at the transition of the gastrocnemius muscle into the
      Achilles' tendon. The pressure difference between active standing and lying is
      defined as the static stiffness index (SSI). RESULTS: The accuracy and precision
      of the probe are good. Unna boot bandages (Lohmann-Rauscher, Vienna, Austria) and
      multilayer short-stretch bandages show a significantly higher SSI than long
      stretch bandages and round-knitted class II stockings. The SSI values are lower
      than 10 mm Hg for elastic, long-stretch material and higher than 10 mm Hg for
      inelastic, short-stretch material. CONCLUSION: In future compression trials,
      pressure and stiffness measured in vivo should be declared.

PMID- 15996411
TI  - Double-blind prospective comparative trial between foamed and liquid polidocanol
      and sodium tetradecyl sulfate in the treatment of varicose and telangiectatic leg
      veins.
AB  - BACKGROUND: Twenty subjects were treated with either polidocanol (POL) or sodium
      tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each
      agent. OBJECTIVE: To determine the safety and efficacy of two widely used
      sclerosing agents. METHODS: After the exclusion of saphenofemoral junction
      incompetency, each subject's leg veins were categorized by size (< 1, 1-3, and 3
      6 mm in diameter). Each leg was then randomized to be treated with 0.5%, 1%, or
      1% foam of POL or 0.25%, 0.5%, or 0.5% foam of STS according to vein size. An
      independent panel of four physicians, blinded to treatment, performed randomized
      photographic evaluations obtained pretreatment and 12 weeks post-treatment.
      Subject satisfaction index and overall clinical improvement assessment were also
      obtained. RESULTS: An average 83% improvement was noted for all vein sizes in all
      subjects with both POL and STS after a single treatment. Subjects were satisfied
      with treatment, regardless of the sclerosing agent used or the vein size treated.
      There was no statistically significant difference in adverse effects between each
      group. CONCLUSION: Both POL and STS are safe and effective sclerosing agents in
      the treatment of varicose and telangiectatic leg veins. Both are very tolerable
      and demonstrate similar post-treatment sequelae.

PMID- 15996412
TI  - Microvascular embolization following polidocanol microfoam sclerosant
      administration.
AB  - BACKGROUND: Intravenous microfoam sclerotherapy solutions can potentially cause
      cerebrovascular arterial embolization. OBJECTIVE: To determine the relationship
      between polidocanol microfoam formulation and arteriolar embolization bubble
      lodging and clearance in vivo. METHODS: Three polidocanol microfoams (one made by
      the double-syringe method using air and two Varisolve (Provensis, Inc., West
      Conshohocken, PA, USA) formulations using different physiologic gas mixtures
      composed primarily of oxygen and carbon dioxide and dispensed from a proprietary
      canister mechanism) were mixed with venous blood and injected into the rat
      cremaster arterial microcirculation. Bubble dimensions and dynamics were recorded
      using intravital microscopy. RESULTS: Bubble entry frequency, size, and dynamics
      depended on microfoam formulation. Air-based bubbles (2.72 1.38 nL; n = 21)
      lodged, obliterating blood flow. Varisolve bubbles (0.20 0.02 nL; n = 2 and 0.53
      0.27 nL; n = 27 for the two gas compositions) entered but either did not lodge or
      cleared within seconds. Bubble size and number were different among these
      microfoams. CONCLUSIONS: Both Varisolve formulations produced smaller embolism
      bubbles than occurred with air-based microfoam. Rapid clearance of Varisolve
      bubbles suggests that they are so small that they do not have adequate surface
      area available for significant binding interactions with arteriolar endothelium.
      Larger air-based bubbles obstruct arteriolar vessels and block blood flow.

PMID- 15996413
TI  - Serum iron and matrix metalloproteinase-9 variations in limbs affected by chronic
      venous disease and venous leg ulcers.
AB  - BACKGROUND: Severe chronic venous disease (CVD) is characterized by both dermal
      hemosiderin accumulation and matrix metalloproteinase (MMP) hyperactivation. The
      iron-driven pathway is one of the recognized mechanisms of MMP hyperactivation.
      OBJECTIVE: To investigate the potential consequences of leg hemosiderin deposits
      on both iron metabolism and activation of MMPs. METHODS: We contemporaneously
      assessed the following in the serum of the arm and ankle veins of 30 patients (C4
      6) with CVD and 14 normal subjects: ferritin, transferrin, iron, percentage of
      transferrin iron binding capacity (%TIBC), and MMP-9. Optical microscopy
      examinations with Perls' staining of chronic wounds were also performed. RESULTS:
      Histology consistently revealed iron deposits. Serum ferritin, iron, and %TIBC
      were significantly increased in the legs affected by severe CVD compared with the
      arm of the same subjects or the controls. In addition, iron and %TIBC were
      significantly elevated in the legs of ulcer patients. The rate of activation of
      MMP-9 was significantly elevated in CVD. CONCLUSIONS: The increased iron
      deposition in legs affected by CVD seems to be more instable in ulcer patients,
      leading to iron release in the serum of the affected leg. Our data suggest the
      iron-driven pathway as a further mechanism for MMP hyperexpression leading to
      tissue lesion.

PMID- 15996414
TI  - Effect of graft size, angle, and intergraft distance on dense packing in hair
      transplant.
AB  - BACKGROUND: The maximum number of hair grafts that can be safely implanted in 1
      cm2 is still debatable. To our knowledge, no previous report has addressed this
      issue in three dimensions, taking into account the size, the angle of the graft,
      and the intergraft distance. OBJECTIVES: To study the effect of the size and
      angle of the graft and the intergraft distance on dense packing. METHODS: Using a
      mathematical formula (the maximum number of hair grafts in 1 cm2 = 33 * cosine),
      the volume of the recipient area and the volume of the hair graft are calculated,
      assuming that the surface area of the recipient area is 1 cm2, the diameter of
      the hair graft is 1 mm, and the intergraft distance is 1.5 mm laterally and 1 mm
      anteriorly and posteriorly. RESULTS: The maximum number of hair grafts that could
      be implanted in 1 cm2 at a 90 angle in relation to the skin surface is 33 grafts,
      at a 60 angle is 28 grafts, and at a 30 angle is 16 grafts. CONCLUSION: The
      maximum number of hair grafts that can be implanted in any given recipient area
      depends on the graft size, the angle or direction of these grafts, and the
      intergraft distance. Where more space is allowed between the grafts, and the more
      acute the angle, the fewer hair grafts that can be implanted.

PMID- 15996415
TI  - Post-Mohs micrographic surgical margin tissue evaluation with permanent
      histopathologic sections.
AB  - BACKGROUND: Incomplete resection of nonmelanoma skin cancer is associated with a
      relatively high rate of recurrent tumors. Mohs micrographic surgery provides
      microscopic evaluation of tumor margins to ensure complete excision of
      nonmelanoma skin cancers at high risk of recurrence. OBJECTIVE: This purpose of
      this study is to confirm the histologic accuracy of Mohs excision of facial skin
      cancers by evaluating an additional layer of tissue with permanent
      histopathologic sections after Mohs excision. METHODS: Two hundred ninety-six
      Mohs cases were identified, which, after excision, were sent to a single plastic
      surgeon for reconstruction. This plastic surgeon routinely takes an additional
      layer and sends for permanent histopathologic evaluation at the time of
      reconstruction. A review of the pathology reports and tissue specimens on these
      patients provides valuable data on tumor margins and the effectiveness of the
      Mohs technique for tumor excision. RESULTS: Two excisions of nodular basal cell
      cancer were determined by the pathologist to have positive tumor involvement on
      post-Mohs permanent tissue. On additional review, one specimen was interpreted to
      be more consistent with follicular epithelium, and the second was verified as a
      focus of nodular basal cell cancer. CONCLUSION: These data support the high
      reliability of Mohs surgery for margin control.

PMID- 15996416
TI  - Long-term clinical outcomes following treatment of actinic keratosis with
      imiquimod 5% cream.
AB  - BACKGROUND: The results from four phase III, randomized, vehicle-controlled
      studies showed that imiquimod 5% cream (imiquimod) was safe and effective in the
      treatment of actinic keratosis (AK). Patients applied imiquimod or vehicle cream
      to AK lesions on the face or balding scalp, dosing three times per week or two
      times per week for 16 weeks. OBJECTIVE: To obtain long-term safety follow-up data
      and estimate AK recurrence in patients who completely cleared their AK lesions in
      the treatment area at the 8-week post-treatment visit in the phase III studies.
      METHODS: One hundred forty-six patients from 30 study centers in the United
      States were evaluated for clinical evidence of AK, and safety data were
      collected. RESULTS: After a median follow-up period of 16 months, 24.7% (19 of
      77) of the patients administered imiquimod three times per week and 42.6% (23 of
      54) of the patients administered imiquimod two times per week had a recurrence of
      AK (the appearance of at least one AK lesion) in the original treatment area. The
      median number of AK lesions present was one lesion for both patients receiving
      imiquimod three times and those receiving imiquimod two times per week compared
      with a median of six lesions at baseline in the combined three times per week and
      two times per week phase III studies. There were no long-term safety issues, and
      the skin quality seen in the imiquimod-treated patients at the end of the phase
      III studies was maintained. CONCLUSION: One and a half years following treatment,
      imiquimod continued to provide a long-term clinical benefit in a majority of
      patients who experienced complete clearance of their AK lesions.

PMID- 15996417
TI  - Gentamicin ointment versus petrolatum for management of auricular wounds.
AB  - BACKGROUND: Surgeons frequently create defects on the ear in the treatment of
      cutaneous malignancies. Potentially significant complications of second-intention
      healing on the ear are suppurative and inflammatory chondritis. Consequently,
      many physicians advocate the use of oral or topical prophylactic antibiotics
      after auricular surgery. OBJECTIVE: The purpose of this study is to compare the
      efficacy of gentamicin ointment with that of petrolatum for the prevention of
      suppurative chondritis during second-intention healing of auricular wounds after
      Mohs surgery. METHODS: One hundred forty-two patients with a total of 147 second
      intention wounds were prospectively selected to receive either gentamicin
      ointment or petrolatum postoperatively. RESULTS: One hundred forty-four wounds
      were evaluated in a follow-up examination or by telephone interview. Eight
      (5.56%) wounds developed suppurative chondritis. Four wounds received gentamicin
      and four received petrolatum, for incidences of 4.76% and 6.67%, respectively.
      Twelve (8.33%) other wounds developed inflammatory chondritis. Ten (11.90%)
      received gentamicin and two (3.33%) received petrolatum. CONCLUSIONS: There is no
      statistically significant difference between the use of gentamicin ointment and
      petrolatum in the prevention of postoperative auricular suppurative chondritis.
      The data also demonstrate a disproportionate number of cases of inflammatory
      chondritis in the gentamicin-treated group. This study supports the cost
      effective and potentially less irritating use of petrolatum for wound care in
      this difficult to manage area.

PMID- 15996418
TI  - Octyl-2-cyanoacrylate liquid bandage as a wound dressing in facial excisional
      surgery: results of an uncontrolled pilot study.
AB  - BACKGROUND: Although cyanoacrylate tissue adhesives are frequently used in the
      closure of cutaneous lacerations and excisions, only a few reports comment on
      their usefulness as a dressing over sutured wounds. A new formulation of octyl-2
      cyanoacrylate (Liquid Bandage; BAND-AID, Johnson & Johnson) is used as an
      occlusive protective film over minor cuts and scrapes. OBJECTIVE: An uncontrolled
      pilot study to assess the safety, efficacy, and cost of Liquid Bandage as an
      occlusive dressing over sutured facial excisions. METHODS: Patients undergoing
      excision of facial neoplasms were recruited. After conventional layered repair,
      Liquid Bandage was applied. On suture removal, the wounds were photographed and
      evaluated by three dermatologists, who assigned an overall outcome rating. The
      average cost of Liquid Bandage and routine wound care materials was calculated
      based on prices from three different pharmacies. RESULTS: Of the 18 wounds
      available at follow-up, 17 were assigned an overall outcome rating of good or
      excellent by at least one of the evaluators. Eleven wounds received an excellent
      rating from at least two of the evaluators. One case of distal flap necrosis
      occurred. Liquid Bandage proved to be less expensive than routine postsurgical
      wound care materials. CONCLUSIONS: Liquid Bandage dressing is safe and effective
      over sutured facial excisions.

PMID- 15996419
TI  - Normal cutaneous wound healing: clinical correlation with cellular and molecular
      events.
AB  - BACKGROUND: Cutaneous wound healing is a normal physiologic function, observed
      and described for centuries by those afflicted with wounds and by those caring
      for them. Recently, tremendous progress has been made in discovering the cellular
      and molecular mechanisms responsible for wound healing. Counseling patients
      appropriately and planning future therapeutic interventions in delayed or
      abnormal wound healing may be improved by a thorough understanding of the
      relationship between clinical, cellular, and subcellular events occurring during
      the normal healing process. MATERIALS AND METHODS: A review of the wound healing
      literature from the past several decades, with a focus on the past 5 to 10 years
      in particular, along with illustrative case examples from our clinical practice
      over the past decade. RESULTS: Traditional clinical stages of wounding healing
      are still relevant, but more overlap between stages is likely a more accurate
      depiction of events. The role of cells such as platelets, macrophages,
      leukocytes, fibroblasts, endothelial cells, and keratinocytes is much better
      known, particularly during the inflammatory and proliferation stages of healing.
      Molecules such as interferon, integrins, proteoglycans and glycosaminoglycans,
      matrix metalloproteinases, and other regulatory cytokines play a critical role in
      the regulation of healing mechanisms. CONCLUSION: Cutaneous wound healing in
      normal hosts follows an orderly clinical process. The scientific underpinnings
      for healing are better understood than ever, although much remains to be
      discovered. Eventually, such improved understanding of cellular and subcellular
      physiology may lead to new or better forms of therapy for patients with acute,
      chronic, and surgical skin wounds.

PMID- 15996421
TI  - Reconstruction of a large surgical defect on the lower eyelid and infraorbital
      cheek.
AB  - An 83-year-old white woman was referred for Mohs micrographic surgery of a
      lentigo maligna on the left malar cheek. The tumor was completely removed in four
      stages, leaving an irregularly shaped defect that measured 3.8 x 4.7 cm and that
      involved the left lower lateral eyelid and infraorbital cheek (Figure 1). How
      would you reconstruct this defect?

PMID- 15996422
TI  - Nasalis flap and graft repair provides reliable closure for denuded defects of
      the nose.
AB  - BACKGROUND: Skin cancer surgery involving the nasal tip and dorsum sometimes
      results in exposure of underlying bone or cartilage. We describe a simple method
      of providing a vascular bed for the defect using the superficial nasalis
      musculoaponeurotic system (SNAS) of the nose, which allows full-thickness skin
      graft reconstruction of the defect and an acceptable cosmetic outcome. OBJECTIVE:
      The utility of nasalis flaps to provide a vascular bed for grafting has not been
      specifically addressed in the dermatology literature. Our experience with 26 SNAS
      flaps is outlined to demonstrate the utility of this closure in the appropriate
      situations. METHODS: A discussion of the relevant anatomy is followed by an
      outline of the surgical technique. RESULTS: SNAS flaps provide a reliable
      vascular bed and contour for defects of the bridge and distal nose. Complications
      have been few. CONCLUSIONS: The SNAS flap and graft are simple to perform and
      provide a reliable alternative to interpolated nasolabial or forehead flaps when
      the defect exposes significant bare cartilage or bone.

PMID- 15996423
TI  - Immediate skin stretching with towel clips and needles.

PMID- 15996424
TI  - Congenital melanocytic nevus: a possible clinical and dermoscopic pitfall.

PMID- 15996425
TI  - Treatment of nevoid hyperkeratosis of the nipple and areola using a
      radiofrequency surgical unit.
AB  - BACKGROUND: Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare
      condition of unknown etiology. Verrucous thickening and pigmentation of the
      nipple and areola are the main features of the condition. Different therapeutic
      options, both medical and surgical, have been described. OBJECTIVE: To use a
      radiofrequency surgical unit to treat an NHNA case, which was unresponsive to
      keratolytic therapy. MATERIALS AND METHODS: The lesions of the nipple and areolas
      were excised tangentially with a diamond-shaped electrode of a radiofrequency
      surgical unit under local anesthesia. RESULTS: The patient had a good cosmetic
      appearance after the treatment, and there was no recurrence at the ninth
      postoperative month. CONCLUSION: Radiofrequency for tangential excision in the
      treatment of NHNA lesions that have not responded to medical therapy can be an
      alternative surgical method.

PMID- 15996426
TI  - Treatment of fireworks tattoos with the Q-switched ruby laser.
AB  - BACKGROUND: The best approach in managing patients with explosive traumatic
      tattoos is the immediate removal of particles during initial care. Delayed
      treatment makes the situation more difficult to manage. Under certain conditions,
      a Q-switched ruby laser can be considered an excellent alternative. METHODS: We
      report a new case of multiple facial fireworks tattooing managed successfully
      with a Q-switched ruby laser under low fluency pulses at 4.5 J/cm2. A
      pretreatment test zone was initially performed, and then three treatments were
      conducted at 6-week intervals. RESULTS: More than 75% of the lesions were removed
      without scarring. CONCLUSION: The Q-switched ruby laser can be a safe and
      excellent choice for the removal of explosive particles.

PMID- 15996427
TI  - Q-switched alexandrite laser therapy for pigmentation of the lips owing to
      Laugier-Hunziker syndrome.
AB  - BACKGROUND: Laugier-Hunziker (LH) syndrome is a rare benign condition in which
      hyperpigmentation of the lips and buccal mucosa occurs with no systemic
      associations. OBJECTIVE: We report the response to treatment with the Q-switched
      alexandrite laser (QSAL) because there are few reports on therapy for LH
      syndrome. METHODS: The QSAL was used for pigmentation of the lips in a 63-year
      old woman with LH syndrome. Laser irradiation was done at 5.0 J/cm2 with a 3 mm
      spot size. RESULTS: There was 100% clearance of pigmentation of the lips with a
      single laser treatment, and recurrence was not observed after 6 months.
      CONCLUSION: The QSAL is very effective for pigmentation owing to LH syndrome.

PMID- 15996428
TI  - Angiolymphoid hyperplasia successfully treated with an ultralong pulsed dye
      laser.
AB  - BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign
      vascular proliferation characterized by dermal or subcutaneous nodules or both,
      primarily in the head and neck. We report the successful treatment of ALHE
      without scarring using a 595 nm ultralong pulsed dye laser, which applies a
      unique combination of longer wavelengths, a longer pulse duration, and a higher
      fluence. OBJECTIVE: To report the use of the 595 nm pulsed dye laser in the
      treatment of ALHE and to detail the particular aspects of this laser that make it
      uniquely qualified to treat this entity. METHODS: Case report and review of the
      literature. RESULTS AND CONCLUSION: This laser may be used as an effective
      treatment for ALHE and has advantages over alternative treatments and older
      lasers. Specifically, the longer wavelength (595 nm) penetrates more deeply into
      dermal tissue, which produces more uniform coagulation across the entire vessel.

PMID- 15996429
TI  - Merkel cell carcinoma arising from the subcutaneous fat of the arm with intact
      skin.
AB  - BACKGROUND: Merkel cell carcinoma is a rare malignant neuroendocrine neoplasm
      characteristically arising from the dermis of sunlight-exposed skin. It rarely
      arises outside the skin. OBJECTIVE: We present a patient with primary Merkel cell
      carcinoma arising from subcutaneous fat, with no involvement of the overlying
      skin. We describe the clinical manifestations and magnetic resonance imaging
      (MRI) findings. METHODS: We report a 63-year-old woman with a primary lesion of
      Merkel cell carcinoma that arose from the subcutaneous fat layer of the left arm.
      The lesion presented as a subcutaneous nodule with intact overlying skin. MRI
      showed that the nodular lesion was located entirely in the subcutaneous fat
      layer, with no involvement of the dermis. Peritumoral infiltration around the
      lesion and enlarged lymph nodes deep to the lesion were noted. The patient
      received wide excision of the lesion with dissection of the regional lymph nodes
      and adjuvant radiotherapy and chemotherapy. RESULTS: Histopathologic examination
      confirmed the diagnosis of Merkel cell carcinoma with local lymphatic metastasis,
      and the lesion was completely located in the subcutaneous fat, with no
      involvement of the dermis. These findings were well correlated with MRI findings.
      CONCLUSION: Primary Merkel cell carcinoma may arise from the subcutaneous fat and
      present as an entirely subcutaneous lesion with intact skin. MRI is helpful to
      evaluate the local extension of the lesion and regional lymphatic metastasis.

PMID- 15996430
TI  - Mixed-type neurothekeoma presenting with an unusual clinical appearance of
      multiple satellite lesions on the back.
AB  - BACKGROUND: Neurothekeoma is a rare cutaneous neoplasm, often occurring as a
      nondescript cutaneous nodule on the central face, shoulders, and upper
      extremities. OBJECTIVE: To present a patient with mixed-type neurothekeoma with
      an unusual clinical presentation. METHODS: We report a 29-year-old female who
      developed an asymptomatic, red, dermal nodule with satellite papules on the back
      over a period of 6 months. RESULTS: The coalescing papules on the back were
      excised, and the histopathology and immunohistochemical study revealed a mixed
      type neurothekeoma. CONCLUSION: Neurothekeoma usually presents with a small,
      solitary, and slow-growing nodule or papule on the upper body. The case is
      interesting because of the unusual clinical manifestation of one dermal tumor
      with several satellite lesions.

PMID- 15996431
TI  - Ungual basal cell carcinoma on the fifth toe mimicking chronic dermatitis: case
      study.
AB  - BACKGROUND: The finger, toe, and nail unit are rare sites of basal cell carcinoma
      (BCC). Only a few patients with BCC of the foot have been described in the world
      literature, and ungual BCC is even less frequent. OBJECTIVE: To discuss through a
      case report the clinical features and diagnosis of BCC of the foot. METHODS: We
      report an unusual case of BCC of the nail unit of the fifth toe of an elderly
      woman that mimicked chronic dermatitis. CONCLUSION: Our case clearly highlights
      the need for biopsy and histopathologic examination whenever we see inflammatory
      lesions with a loss of substance that are refractory to systemic or topical
      treatments.

PMID- 15996432
TI  - Successful treatment of recurrent pilonidal sinus with laser epilation.
AB  - BACKGROUND: Pilonidal disease is a chronic disease of the natal cleft. Recurrent
      follicular infection is the causative factor. Surgical treatment has a
      significant failure rate, and recurrence is common. Laser removal of hair in the
      natal cleft could be an alternative to surgery. OBJECTIVE: To determine the
      effectiveness of laser hair removal in the natal cleft on pilonidal disease.
      METHODS: Six young men with recurrent pilonidal disease were treated with laser
      epilation in our clinic from 2000 to 2003. Most patients had a history of one or
      more surgical treatments in the area, and all patients had suffered recurrent
      folliculitis for years. An alexandrite laser was mostly used, although,
      occasionally, an intense pulsed light device was used. The number of epilation
      treatments ranged from 3 to 11, performed at 6- to 8-week intervals. RESULTS: All
      patients experienced progressive resolution of the folliculitis with the laser
      epilation treatments. No more surgical treatments have been needed. The
      treatments were simple and quick, and there were no complications. CONCLUSION:
      Laser epilation of the natal cleft should be considered a first choice treatment
      for recurrent pilonidal disease. Preventive laser epilation of the natal cleft in
      patients with recurrent folliculitis could avoid future surgery.

PMID- 15996433
TI  - British-style digital tourniquet.

PMID- 15996434
TI  - Single-layer closure of scalp wounds.

PMID- 15996435
TI  - Elephantiasis nostras verrucosa treated with surgical debridement.

PMID- 15996436
TI  - Re: intravascular 1,320 nm laser closure of the great saphenous vein: a 6- to 12
      month follow-up study.

PMID- 15996437
TI  - Tsunami and the role of the international travel health community.

PMID- 15996438
TI  - Help tsunami victims--be a tourist!

PMID- 15996439
TI  - Review of 1 year's activity in the Grampian travel clinic: the importance of the
      oil industry.
AB  - BACKGROUND: A review of the activities of the Grampian travel clinic was carried
      out over 1 year to obtain an overall perspective of the clinic workload and to
      determine how much of the workload was dependent on the oil industry. METHODS: A
      specially designed data collection sheet was completed for each of the 669
      consultations conducted at the Grampian travel clinic, Aberdeen, between February
      1, 2002, and January 31, 2003. RESULTS: Patients attending the clinic came in
      equal numbers from the city of Aberdeen and the Grampian region. Twenty-five
      percent were traveling for work purposes: 87.4% of this travel was oil related,
      and most patients were headed to Africa. The commonest vaccines given were for
      yellow fever, Japanese B encephalitis, and rabies, reflecting the specialist
      nature of the clinic. Most travelers did leave adequate time for immunization
      before travel. The public is still apprehensive about using mefloquine as
      malarial prophylaxis. CONCLUSIONS: Most attendees were traveling on holiday, but
      a quarter of the consultations were for travel related to the oil industry.
      Almost 70% of attendees had already visited their general practitioner and were
      therefore attending the clinic for specialist advice and vaccines. There is a
      need for increased clinic capacity.

PMID- 15996440
TI  - Pharmacodynamic analysis of antimalarials used in Plasmodium falciparum imported
      malaria in northern Italy.
AB  - BACKGROUND: Conventional treatment of imported malaria in Italy consists of
      quinine or mefloquine. Since beta-arthemeter is now available, an open-label
      pharmacodynamic analysis was performed in 73 adults with uncomplicated Plasmodium
      falciparum malaria. In vitro susceptibility to mefloquine and quinine was
      evaluated at admission. METHODS: According to clinical status, baseline
      parasitemia (P(0)), and premunition, the patients received intravenous quinine,
      oral mefloquine, or beta-arthemeter. The following parameters were measured:
      parasitemia at 0, 6, 12, and 24 hours and then every 24 hours until negative;
      time to 50%, 90%, and 100% reduction in parasite density (PC(50), PC(90), and
      PCT); parasite reduction ratio at 24 and 48 hours (PRR(24) and PRR(48));
      percentage of patients with undetectable parasitemia at 48 hours (PPUP(48)); time
      required to eradication; in vitro susceptibility to mefloquine and quinine by
      World Health Organization Microtest Mark III. RESULTS: Of the study patients,
      54.8% were immigrants from malaria-endemic countries. All the infections were
      acquired in Africa. All the patients were treated successfully. According to the
      pharmacodynamic parameters measured, no significant differences were recorded
      among patients with or without prior exposure to malaria. Pharmacodynamic
      comparison was performed between quinine and beta-arthemeter. Significantly
      higher clearance times were recorded for beta-arthemeter vs quinine (PC(50),
      PC(90), and PCT: 16.8, 42.6, and 72 h for quinine vs 7.9, 12.2, and 48 h for beta
      arthemeter; p values: .02, < .0001, and .008, respectively). The number of
      patients who obtained a PPUP(48) with beta-arthemeter was higher than with
      quinine (66.7 vs 9.1%, p < .003), and PRR(24) was significantly higher in beta
      arthemeter-treated patients (617 vs 3.15, p = .0001). PRR(48) and time to
      eradication were not measurable in the beta-arthemeter group (negative P at 48 h
      in most cases). Two recrudescences occurred after 5 and 7 days of beta-arthemeter
      monotherapy. All strains were fully susceptible to quinine and mefloquine.
      CONCLUSIONS: Pharmacodynamic properties of mefloquine and quinine are in the
      range reported in literature. The better PCT and pharmacodynamics of beta
      arthemeter suggest that it could be used as a first-line agent, coadministered
      with mefloquine.

PMID- 15996441
TI  - Adequate primaquine for vivax malaria.
AB  - BACKGROUND: Treatment of vivax malaria with primaquine prevents the relapse of
      infection from residual liver stages of the parasite. Inadequate dosage is
      related to a higher relapse risk. METHODS: A comparison was made of vivax malaria
      relapse-prevention treatments with primaquine 22.5 mg or 30 mg daily for 14 days
      on 146 reports to the Australian Army Central Malaria Register. RESULTS: The
      lower dose of primaquine was found to carry a relative risk of 6.63 for a relapse
      of vivax malaria compared with the higher dose. CONCLUSIONS: The available data
      presented here suggest that vivax malaria in this region is increasingly tolerant
      of the 22.5 mg daily treatment regimen of primaquine and that the greater dose of
      at least 30 mg daily is more effective.

PMID- 15996442
TI  - Epidemiology of travel-related hospitalization.
AB  - BACKGROUND: Limited information exists on causes of hospitalization in patients
      returning from the tropics, and most is focused on febrile diseases. We evaluated
      all causes of post-travel hospitalization in a tertiary care hospital in Israel.
      METHOD: Demographics, diagnoses, and destinations of patients admitted between
      January 1999 and December 2003 with a history of recent travel were recorded.
      Demographics and destination of healthy travelers presenting to our pretravel
      clinic at the same period were recorded. RESULTS: Of 211 patients admitted, 71%
      were males, 8% were immigrants/foreign workers, and febrile diseases accounted
      for 77% of admissions. The most common diagnoses were malaria in 54 (26%),
      unidentified febrile disease in 34 (16%), and dengue fever in 27 (13%). New World
      cutaneous leishmaniasis was the most common cause of admission among nonfebrile
      patients (18 [9%]). Diarrheal diseases accounted for only 11% of admissions.
      Regarding destination, 101 (48%) patients had been to Asia, 71 (34%) to Africa,
      and 43 (20%) to the Americas. Of our healthy traveler population, 59% traveled to
      Asia, 20% to Africa, and 20% to the Americas. Travel to Africa carried the
      highest risk of being hospitalized (OR 1.85, 95% CI 1.16-2.97; p = .01). Most
      (59%) patients returning from Africa had malaria. The principal health problem
      originating in Asia was dengue fever (27%), and from Latin America, cutaneous
      leishmaniasis (48%). Males comprised 71% of the patients, and 59% of the healthy
      traveler population (p < .0001). Males were more likely to acquire malaria (OR
      2.15, 95% CI 1.13-4.09; p = .02) and leishmaniasis (OR 3.41, 95% CI 0.97-11.89; p
      = .05). CONCLUSIONS: Febrile diseases were the most common cause for
      hospitalization, with malaria, unidentified febrile diseases, and dengue fever
      being the most common. Diseases were destination related; travel to Africa was
      associated with a higher rate of hospitalization. Malaria and cutaneous
      leishmaniasis had a substantially male predominance, probably due to risk-taking
      behavior.

PMID- 15996443
TI  - Traveler's thrombosis: a systematic review.
AB  - BACKGROUND: Anecdotal evidence suggests a possible link between travel and venous
      thromboembolism (VTE). We systematically evaluated the evidence from
      observational studies. METHODS: We searched studies evaluating the risk of venous
      thrombosis in relation to traveling from MEDLINE and EMBASE up tp March 2004,
      together with a hand search of reference lists from retrieved literature, and we
      contacted some of the experts. Observational studies estimating the risks of VTE
      and isolated calf vein thrombosis were eligible. Methodologic quality was
      assessed based on prior criteria, and meta-analysis was considered where
      applicable. RESULTS: A total of 194 English-language publications were initially
      identified. Sixteen studies were included: 9 case-control, 2 prospective
      controlled, and 5 other observational studies. They differed drastically in study
      designs, selection of controls where applicable, mode and duration of travel, and
      subtypes of VTE under consideration. Ten studies concluded that travel, mostly
      through air and of prolonged duration, is a risk factor for venous thrombosis
      and/or pulmonary embolism, and the risk increases for passengers with preexisting
      venous thrombosis risk factors. Outcomes examined ranged from asymptomatic
      isolated calf muscle vein thrombosis to severe fatal pulmonary embolism.
      CONCLUSIONS: Current literature is controversial over any association between
      travel and VTE, and although the quality and power of these studies have been
      variable, studies of higher quality have shown a strong and significant
      association between prolonged air travel and VTE. No conclusions could be drawn
      about other modes of transportation. Since VTE is a disease of multifactorial
      causation, those with preexisting VTE risk factors are most vulnerable.

PMID- 15996444
TI  - Change in epidemiology of malaria infections in a rural area in Ethiopia.
AB  - We describe a change in epidemiology of 3,615 cases of malaria in a rural area in
      Ethiopia (from September 11, 1998, through September 10, 2003). The Plasmodium
      falciparum infection increased from 40.9% in the first year to 73.4% in the last
      year, and the Plasmodium vivax infection decreased from 54.7% to 22.4% (p <
      .001).

PMID- 15996445
TI  - Lyme risk for immigrants to the United States: the role of an educational tool.
AB  - New immigrants to Lyme-endemic areas of the United States are unaware of this
      infection. This study, which took place in a community with a large population of
      new immigrants, demonstrated a lack of awareness of Lyme disease. A short
      educational tool was proven effective in increasing recognition.

PMID- 15996446
TI  - Leprosy in a backpacker.
AB  - Leprosy is the most common cause of peripheral neuropathy in the developing
      world. It is not expected to be acquired by visitors traveling through these
      countries. We present a backpacker who contracted leprosy during brief stays in
      endemic countries.

PMID- 15996447
TI  - Medical conditions affecting well-accommodated travelers in Lebanon.
AB  - There are no data on the prevalence of common diseases affecting travelers to
      Lebanon. Between 2001 and 2002, one among nine physicians was consulted on guests
      who needed medical attention in a five-star Beirut hotel. Physicians were
      consulted 114 times. The mean age of the patients was 36.6 years. Gastroenteritis
      (50.9%) followed by respiratory problems (25.4%) were the leading causes for
      consultation.

PMID- 15996449
TI  - Pretravel health advice among international travelers visiting Cuzco, Peru.
AB  - BACKGROUND: Cuzco, a Peruvian city of historical interest located 3,326 m above
      sea level, is a frequent destination for tourists. We conducted a descriptive
      study to assess the extent and sources of pretravel health advice received by
      international travelers before their arrival to Cuzco. METHODS: Data were
      collected as part of a health survey among travelers. Between August and November
      2002, travelers between 15 and 65 years old were invited to fill out a
      questionnaire in the departing area of Cuzco's international airport. RESULTS: A
      total of 5,988 travelers participated. The mean age was 35.4 years (SD 11.4 yr);
      50.6% were female and 50.8% were single. Tourism was the reason for traveling in
      90.2% of the participants, and 89.3% of them were traveling with companions.
      Pretravel health information was received by 93.6%. The median number of
      information sources was two, with books (41.5%), travel medicine clinics (38.8%),
      the Internet (23.3%), and general practitioners (22.7%) as the main sources. Most
      frequently received recommendations were about safe food and water consumption
      (85%), use of insect repellents (66.0%), sunburn protection (64.4%), and condom
      use (22%). Only 16.5% took medication to prevent altitude sickness, and 14.2%
      took medication to prevent traveler's diarrhea. Variables independently
      associated with receiving pretravel health information from a health care
      professional were female gender, country of residence other than the United
      States, length of stay in Cuzco > 7 days, length of stay in other Peruvian cities
      > 7 days, tourism as the main reason for visiting Cuzco, traveling with
      companions, and consulting of more than one source of information. CONCLUSIONS:
      Most travelers arriving to Cuzco had received pretravel health information, and
      the majority obtained it from more than one source. Recommendations addressed for
      specific health risks, such as altitude sickness prophylaxis, were received by
      few travelers.

PMID- 15996450
TI  - Willingness to pay for preventive travel health measures among Hong Kong Chinese
      residents.
AB  - BACKGROUND: The effectiveness of preventive measures in combating travel-related
      illnesses is well recognized. However, there is a lack of information on the
      economic value of any travel-associated preventive measures in the literature.
      OBJECTIVES: The purpose of this article is to report the values of willingness to
      pay (WTP) to prevent travel health problems in Hong Kong's travelers. METHODS: A
      cross-sectional telephone survey for a sample of Hong Kong population was
      conducted in 1998 using a random digit dialing technique. The sample WTP values
      were elicited using an open-ended question. Logistic regression was performed to
      identify predictors of WTP. Mean WTP was estimated using Heckman's sample
      selection model on log-WTP. RESULTS: Of the subjects interviewed, 77% (285/369)
      offered positive values of WTP to prevent travel health problems. The observable
      WTP (zero excluded) had a higher mean (447 Hong Kong dollars) than did the zero
      inclusive data (351 Hong Kong dollars). The median values were 200 Hong Kong
      dollars in both cases because there were a large number of protest responses.
      Age, travel frequency, ability to assess travel health risk, precautionary
      behavior, and previous exposure to health protection materials explained one's
      willingness to pay a positive amount for preventing travel health problems. Age,
      education level, and precautionary behavior were predictors of the WTP levels.
      CONCLUSION: The findings of this study suggest that Chinese travelers are willing
      to pay for the prevention of travel-related illnesses. The predictors of WTP
      identified could be used to suggest policy changes. However, future studies are
      needed to explore further the relationship between the experience of travel
      illnesses, the magnitude of travel health risks, and WTP.

PMID- 15996451
TI  - Factors influencing the pattern of imported malaria.
AB  - BACKGROUND: Data on imported malaria in industrialized areas are known to be
      incomplete because of underreporting and lack of homogeneity. These facts and the
      complexity of factors influencing the transmission of malaria render their
      interpretation difficult. The relevance of various factors is usually not fully
      considered, although their impact on recommendations for chemoprophylaxis may be
      important. METHODS: All malaria cases imported from Kenya from 1988 to 1996 that
      were reported to the Federal Office of Public Health of Switzerland were
      analyzed. The reciprocal impact on data interpretation with regard to Plasmodium
      species, chemoprophylaxis, onset of first symptoms after return, male or female
      sex, seasonal fluctuation, duration of stay, nationality groups, and fatal
      outcome was analyzed. RESULTS: Multivariate analysis showed a significant impact
      of Plasmodium species, regular chemoprophylaxis, and long duration of stay on the
      latency of malaria attacks. African origin and repeated stays were confounders
      with regard to adherence to chemoprophylaxis. The local situation of malaria
      transmission and the development of tourist figures were found to influence the
      evolution of malaria rates. These factors must be analyzed simultaneously to
      prevent errors in data interpretation. A higher proportion of tertian malaria
      cases (caused by Plasmodium vivax or Plasmodium ovale) than in previous reports
      was recorded owing to the impact of chemoprophylaxis and longer outbreak
      latencies. Seventy-five percent of tertian malaria cases were diagnosed within 6
      months after return. CONCLUSIONS: Factors influencing the pattern of imported
      malaria must be assessed in relation to each other, especially if data from
      different countries and various chemoprophylaxis regimens are compared.
      Furthermore, regular malaria chemoprophylaxis with mefloquine given until 4 weeks
      after return from an endemic area is not adequate to prevent tertian malaria.
      Regular chemoprophylaxis was found to cause longer latencies for all malaria
      species.

PMID- 15996452
TI  - Imported strongyloidosis: a longitudinal analysis of 31 cases.
AB  - BACKGROUND: Attention regarding imported tropical diseases is typically focused
      on malaria, although other parasitic diseases such as strongyloidosis may also
      cause serious health problems. The importance of assessing clinical features and
      of proper diagnosis and treatment is presented on the basis of 31 patients with
      imported strongyloidosis. METHODS: A retrospective analysis was performed
      regarding patients treated for strongyloidosis in two referral centers in
      Switzerland from 1998 to 2002. RESULTS: Imported strongyloidosis was investigated
      in 12 travelers and 19 immigrants. The reasons for diagnostic work-up were
      clinical symptoms in 84% and eosinophilia and screening in each of 22.5%. All
      patients had a history of travel or residence in endemic areas. Initial therapy
      was effective in 20 patients, and there was a tendency for a better response to
      ivermectin compared with the response to other drugs. A significant reduction in
      blood eosinophil count and serologic antibody titer was observed in patients
      responding to therapy after an average of 96 and 270 days, respectively.
      CONCLUSIONS: Strongyloidosis must be suspected in travelers and immigrants with
      skin or abdominal symptoms from regions where Strongyloides stercoralis is highly
      endemic. The results of this case series confirm that ivermectin is the drug of
      choice in treating imported strongyloidosis. Response to therapy can be assessed
      by serology and differential white blood count performed over 6 months after
      therapy.

PMID- 15996453
TI  - Protection against tick-borne encephalitis with a new vaccine formulation free of
      protein-derived stabilizers.
AB  - BACKGROUND: Vaccination against tick-borne encephalitis (TBE) has been
      successfully employed for many years in TBE-endemic countries. Post-marketing
      experience gained from widespread use, however, prompted the development of
      improved TBE vaccines, the most modern versions of which do not contain the
      commonly used protein-derived stabilizers (human albumin or polygeline) of former
      vaccines. METHOD: This article summarizes both the medical need for and clinical
      experience with a new TBE vaccine formulation (pediatric and adult versions). To
      this end, data from clinical trials and post-marketing experience are presented.
      The clinical database comprises immunogenicity and/or safety data of
      approximately 7,500 subjects ages 1 to 77 years who participated in eight
      clinical trials. The clinical trials were conducted at 69 centers in five
      European countries. Post-marketing experience includes safety data from passive
      pharmacovigilance systems in 18 countries where these vaccines have been licensed
      since 2001. RESULTS: All subjects analyzed for immunogenicity achieved
      postimmunization levels of TBE antibodies that meet the definition of
      seroconversion or represent a fourfold increase. The pooled data of clinical
      trials revealed the expected rate of solicited local and systemic reactions. The
      majority of these transient postimmunization reactions were mild.
      Pharmacovigilance data confirm the high level of safety of these new TBE
      vaccines: only a common range of the side effects already noted for licensed TBE
      vaccines was reported. After the distribution of more than five million vaccine
      doses, no potential safety risk was noted. CONCLUSION: Post-marketing experience
      supports results from clinical trials showing that these new TBE vaccines may
      safely be used for the vaccination of children, adolescents, and adults.

PMID- 15996454
TI  - Effect of vacation on health: moderating factors of vacation outcome.
AB  - BACKGROUND: Vacation has recently become a topic of interest in health research
      as both beneficial and adverse health effects have been documented. The present
      study was aimed at identifying vacation characteristics predicting health-related
      vacation outcome. METHODS: One hundred ninety-one predominantly white-collar
      employees (109 female, 82 males; mean age 37.8 yr, range 16-62 yr) received a
      questionnaire in the week after vacation assessing subject characteristics,
      physical vacation characteristics, the individual structuring of the day, health
      and social behavior, and stress during vacation as well as the perceived change
      of recuperation and exhaustion from before to after a vacation. Regression
      analysis was used to identify variables predicting vacation outcome. RESULTS:
      Twenty-seven percent of the variance of the change of recuperation and 15% of the
      change of exhaustion could be explained. Recuperation was facilitated by free
      time for one's self, warmer (and sunnier) vacation locations, exercise during
      vacation, good sleep, and making new acquaintances, especially among vacationers
      reporting higher levels of prevacation work strain. Exhaustion was increased by
      vacation-related health problems and a greater time-zone difference to home, and
      was reduced by warmer vacation locations. CONCLUSION: Health-related vacation
      outcome is significantly affected by the way an individual organizes his or her
      vacation.

PMID- 15996455
TI  - Vaccination against enterotoxigenic Escherichia coli, a cause of travelers'
      diarrhea.

PMID- 15996456
TI  - Suppurative epididymo-orchitis and chronic prostatitis caused by Burkholderia
      pseudomallei: a case report and review.

PMID- 15996457
TI  - Provider-pharmacist education and adherence rates for the oral typhoid vaccine: a
      pilot study.
AB  - In 2002, 35 travelers were surveyed regarding the travel medicine provider and
      pharmacist education they received, along with self-reported adherence rates for
      the Ty21a vaccine. The results demonstrated that pharmacy education is minimal
      and that computerized pharmacy education handouts were not considered helpful by
      these travelers. Complete adherence was reported at 49%.

PMID- 15996459
TI  - Schistosomiasis: an underestimated problem in industrialized countries?

PMID- 15996460
TI  - Schistosome infection among river rafters on Omo River, Ethiopia.
AB  - BACKGROUND: Adventure trips to Africa have become more frequent, and rafting on
      some of the great rivers has become almost commonplace. We describe three rafting
      trips on the Omo River in Ethiopia, after which most of the participants were
      diagnosed with schistosomiasis. METHODS: After index cases from the three groups
      came to medical attention, active surveillance detected outbreaks of illness in a
      group of American travelers (n = 18 ) in 1993 and in two groups of Israeli
      travelers in 1997 (n = 26). RESULTS: Of 44 travelers, 37 were screened and 28
      (76%) were infected, all with Schistosoma mansoni. Among the infected patients,
      16 of 28 (57%) were symptomatic, the most frequent manifestation being fever,
      which occurred in 14 of 25 (56%); cough occurred in 6 of 18 (33%). Diagnosis was
      based on FAST-enzyme-linked immunosorbent assay, with confirmation by immunoblot.
      Other rafting trips on the Omo River sponsored by the same tour companies did not
      result in symptomatic infection. Investigation of the rafting itineraries
      suggested the route may have been altered from the usual for these three groups,
      exposing them to a part of the river that is wider, slower moving, and more
      densely populated. CONCLUSIONS: Schistosomiasis should be considered in febrile
      patients following rafting trips in schistosome-endemic areas. As asymptomatic
      schistosomiasis in travelers is also common (43% in this series), all travelers
      exposed to freshwater in endemic areas should be encouraged to undergo serologic
      screening.

PMID- 15996461
TI  - Presentation and diagnosis of imported schistosomiasis: relevance of
      eosinophilia, microscopy for ova, and serology.
AB  - BACKGROUND: In nonendemic countries a steady rise in cases of imported
      schistosomiasis has been observed. The objective of this study was to describe
      the presentation of patients diagnosed with schistosomiasis in the Outpatient
      Department (OPD) for Tropical Diseases in the Academic Medical Center, Amsterdam,
      the Netherlands. METHODS: In a retrospective study, patients with schistosomiasis
      from our OPD (1997-1999), including a subgroup of persons asking for screening
      for schistosomiasis and found positive, were analyzed. Diagnosis was based on
      freshwater exposure in an endemic area and positive serology for schistosomal
      antibodies. The following data were recorded: age, gender, country of birth,
      travel destination, symptoms, eosinophil count, and results of serology and stool
      and urine microscopy. RESULTS: Seventy-eight patients (42 travelers, 16
      expatriates, and 20 immigrants) were diagnosed with schistosomiasis; 47% were
      infected in southern Africa. Twenty-four percent had specific symptoms, 57% had
      eosinophilia, and in 17 patients (22%) Schistosoma ova were found. Eleven
      travelers suffered from Katayama syndrome. Of the subgroup of 42 persons screened
      for schistosomiasis, 15 (36%) had schistosomal antibodies; the majority of these
      persons (10/15 [67%]) were infected in southern Africa. CONCLUSION: In our OPD
      schistosomiasis was diagnosed in about 26 patients per year, 3% of all new
      presentations. Infections were almost exclusively acquired in Africa. In
      travelers high eosinophilia was due to acute schistosomiasis; in immigrants it
      was due to concomitant helminthic infections. One of three people asking to be
      screened for schistosomiasis had schistosomal antibodies. Eosinophilia was
      indicative but an insufficient screening tool, and stool and urine microscopy for
      ova were not sensitive. Screening by serology is easy and reliable and the method
      of choice in asymptomatic persons with a history of freshwater exposure in a high
      risk area.

PMID- 15996462
TI  - Postexposure chemoprophylaxis for occupational exposure to human immunodeficiency
      virus in traveling health care workers.
AB  - BACKGROUND: There has been little research on the use of human immunodeficiency
      virus (HIV) postexposure prophylaxis (PEP) for occupational exposure in traveling
      health care workers (HCWs). Although PEP is the standard of care for occupational
      exposure to HIV in the United States, in third-world countries such medications
      are often unavailable and risks to the HCW may be higher. The aims of this study
      were to assess the incidence and types of blood and body fluid exposure and
      subsequent use of PEP in traveling HCWs seen at a large travel clinic prior to
      travel. METHODS: To determine the utility of PEP, we retrospectively evaluated
      all HCWs presenting for counseling prior to travel for health care delivery. All
      employees who were seen at the Mayo Travel and Tropical Medicine Clinic from 1999
      until July 2002 were included. Analysis was conducted via a chart review as well
      as an approved questionnaire mailed to all employees still at the Mayo Clinic.
      RESULTS: Eighty-six HCWs were included in the analysis, and 58 responded to the
      questionnaire. Of the 86 HCWs reviewed, 55 (64%) were determined to be at high
      risk for occupational exposure to HIV. Seventy-eight percent of the high-risk
      HCWs were documented to have been counseled about needlestick avoidance, and 55%
      brought PEP with them. In the 58 HCWs who returned the questionnaire, there were
      no reported deep needlesticks. One of the 39 high-risk HCWs who returned the
      questionnaire (2.6%) had a superficial needle exposure, but the source patient
      had pretested negative for HIV and therefore the HCW did not use PEP. Nine of the
      39 (23%) had a blood splash onto intact skin, and one of these involved a large
      volume. This source patient also had pretested negative for HIV. None of the HCWs
      exposed to blood splash took PEP. Two HCWs (5.1%) at high risk had an exposure
      that would have required PEP if the source patient had not been pretested.
      CONCLUSIONS: Needlestick exposure and HIV PEP counseling is important for HCWs
      traveling for health care delivery. Exposure risks appear low but high enough to
      warrant supplying high-risk HCWs with PEP. HCWs are able to use the
      recommendations appropriately. Pretesting of surgical patients decreases the
      likelihood of starting PEP. Carrying a common supply of PEP for a larger group
      can decrease the cost of PEP.

PMID- 15996463
TI  - Human immunodeficiency virus acquired heterosexually abroad: expert panel
      assessment of the "indigenous/nonindigenous to the United kingdom status" of
      cases.
AB  - BACKGROUND: In Scotland the proportion of human immunodeficiency virus (HIV)
      diagnosed patients who were presumed to have acquired their infection abroad
      increased from 4% (12/269) in 1985 to 34% (53/154) in 2000. Several journalists
      and health professionals assumed that this increase in diagnosis rate reflected
      HIV among persons from Scotland who had acquired their infection while traveling
      abroad. Because of limitations in HIV surveillance data quality, no attempt had
      been made to distinguish diagnosed persons who were indigenous to the United
      Kingdom from those who were not. To address this problem, the investigators set
      out to interpret the existing surveillance data using a probability-based
      judgment approach. METHODS: A panel of travel medicine experts was employed to
      generate a judgment on reported heterosexual cases, presumed to have acquired HIV
      abroad and diagnosed before 2001, as to their likelihood of being indigenous to
      the United Kingdom (I) or not (NI). Median score thresholds were set to produce a
      range of possible values of I as a proportion of I + NI. RESULTS: For diagnoses
      made during 1991 to 1995, the possible value of I as a proportion of I + NI
      ranged between 17% (5/29) and 34% (23/68); for 1996 to 2000, the range was 32%
      (39/123) to 33% (43/130). Overall, 15% of cases were unclassifiable. Thus, up to
      one-third of HIV-diagnosed heterosexuals who likely acquired their HIV abroad
      originated in Scotland. CONCLUSIONS: Amid current publicity about infections
      among immigrants, the distinction between I and NI group sizes should better
      inform public health professionals for resource allocation to prevent new HIV
      infection among indigenous persons, and for the health care of nonindigenous
      persons entering Scotland with HIV. Using classification criteria derived from
      this study, there are plans to publish such data routinely in the context of
      national surveillance.

PMID- 15996464
TI  - Vaccines in travel health: from risk assessment to priorities.

PMID- 15996465
TI  - Influenza: changing approaches to prevention and treatment in travelers.

PMID- 15996466
TI  - Educational issues and concerns in travel health advice: is all the effort a
      waste of time?

PMID- 15996467
TI  - Medical problems in cycling tourism.

PMID- 15996468
TI  - Acute hepatitis C virus infection after a travel in India.

PMID- 15996469
TI  - Comparing neutron and X-ray-based dual beam gauges for characterising industrial
      organic-based materials.
AB  - Comparisons are made of the neutron gamma transmission (NEUGAT) and dual energy X
      ray absorption (DEXA) methods of measuring the composition of organic-based
      industrial products. A simple model is developed to allow comparisons to be made
      particularly of the measurement precision and the industrial performance. These
      gauges have similar applications but the latter gauge is shown to be more
      suitable for high and variable product throughputs. X-ray tube source and
      detector combinations provide higher beam fluxes, superior imaging and require
      less bulky shielding.

PMID- 15996470
TI  - Advanced gamma ray technology for scanning cargo containers.
AB  - The shipping industry is striving to increase security for cargo containers
      without significantly impeding traffic. Three Science Applications International
      Corporation (SAIC) development programs are supporting this effort. SAIC's ICIS
      system combines SAIC's VACIS gamma ray imaging, radiation scanning, OCR,
      elemental analysis and other technologies to scan containers for nuclear
      materials and other hazards in normal terminal traffic. SAIC's enhanced gamma ray
      detector improves VACIS image resolution by a factor of three. And SAIC's
      EmptyView software analyzes VACIS images to automatically verify empty
      containers.

PMID- 15996471
TI  - Uncertainty in rate loss corrections based on counting a periodic pulser.
AB  - Tomographic gamma scanning of waste produces three-dimensional transmission and
      emission images. These are used to derive item-specific attenuation correction
      factors that improve the accuracy of non-destructive waste assay. For each
      vertical layer, data grabs of short duration are acquired as the waste item is
      rotated and translated. The image reconstruction demands accurate rate loss
      corrections to minimize assay bias. For this application a pulser was used to
      perform the necessary rate loss corrections. In this work, we summarize the
      benefits of the pulser approach and review the basic principles on which the
      method is based. We extend the treatment to include a derivation of the
      expression for the uncertainty in the net pulser peak area in the presence of an
      underlying continuum. We report experimental results, taken using a Canberra
      model WM2900 Tomographic Gamma Scanner, over a broad range of count-rates and
      peak-to-continuum ratios. Repeat counts under controlled conditions allowed the
      correction factor and its variance to be determined and compared against
      expectations. These results confirm the validity of the correction factor formula
      and the corresponding expression for its uncertainty. The rate loss analysis has
      been built into a Monte Carlo Replicate engine to allow the uncertainty to be
      propagated into the total measurement uncertainty of the final assay.

PMID- 15996472
TI  - Electronic microscopy and EDX characterization of Teotihuacan prehispanic mortar
      from the cave under the Sun Pyramid.
AB  - A cave (102 m long) under the structure of the Sun pyramid of the prehispanic
      Teotihuacan City indicates the importance of the pyramid. Studies of the cave
      mortar samples using energy dispersive X-ray (EDX) fluorescence, scanning
      electron microscopy (SEM) and X-ray diffraction (XRD) showed no difference in the
      chemical elemental composition. The elements can be distributed in three groups:
      major, minor and trace elements. The minerals identified were compatible with the
      origins of the cave and with the magnetic pattern.

PMID- 15996473
TI  - Thermoresponsive polymers as promising new materials for local radiotherapy.
AB  - We describe a novel thermoresponsive polymeric drug delivery system based on
      poly(N-isopropylacrylamide) with isotopically labellable end groups [l
      tyrosinamide or diethylenetriaminepentaacetic acid (DTPA)] designed for local
      radiotherapy. The polymers are readily soluble in isotonic aqueous sodium
      chloride at room temperature and the phase separation is complete at body
      temperature as proved by DSC measurements. Sufficent binding capacity for
      radionuclides and chemical stability are demonstrated on 125I and 90Y-labelled
      polymers.

PMID- 15996474
TI  - Quantitative NDA of isotopic neutron sources.
AB  - A non-destructive method for assaying transuranic neutron sources was developed,
      using a combination of gamma-spectrometry and neutron correlation technique.
      Source strength or actinide content of a number of PuBe, AmBe, AmLi, (244)Cm, and
      (252)Cf sources was assessed, both as a safety issue and with respect to
      combating illicit trafficking. A passive neutron coincidence collar was designed
      with (3)He counters embedded in a polyethylene moderator (lined with Cd)
      surrounding the sources to be measured. The electronics consist of independent
      channels of pulse amplifiers and discriminators as well as a shift register for
      coincidence counting. The neutron output of the sources was determined by gross
      neutron counting, and the actinide content was found out by adopting specific
      spontaneous fission and (alpha,n) reaction yields of individual isotopes from the
      literature. Identification of an unknown source type and constituents can be made
      by gamma-spectrometry. The coincidences are due to spontaneous fission in the
      case of Cm and Cf sources, while they are mostly due to neutron-induced fission
      of the Pu isotopes (i.e. self-multiplication) and the (9)Be(n,2n)(8)Be reaction
      in Be-containing sources. Recording coincidence rate offers a potential for
      calibration, exploiting a correlation between the Pu amount and the coincidence
      to-total ratio. The method and the equipment were tested in an in-field
      demonstration exercise, with participation of national public authorities and
      foreign observers. Seizure of the illicit transport of a PuBe source was
      simulated in the exercise, and the Pu content of the source was determined. It is
      expected that the method could be used for identification and assay of illicit,
      found, or not documented neutron sources.

PMID- 15996475
TI  - Dopaminergic neurotoxins require excitotoxic stimulation in organotypic cultures.
AB  - We have investigated the properties of the dopaminergic neurotoxins 6
      hydroxydopamine, 1-methyl-4-phenylpyridinium and rotenone using an organotypic
      culture that included slices of substantia nigra, striatum and cortex maintained
      for about 20 days in vitro. At this age, the organotypic culture contains
      dopaminergic neurons, visualized using tyrosine hydroxylase (TH)
      immunohistochemistry, that project into the striatal slice and extend up to 1 mm
      into the cortical slice. Using TH immunohistochemistry to assess survival of
      dopaminergic neurons, we found that the three dopaminergic toxins alone were not
      selectively neurotoxic. However, the addition of a low concentration of N-methyl
      d-aspartate together with each individual toxin resulted in profound injury to
      the dopaminergic neurons, reflected by the loss of cell bodies and the
      fragmentation of processes. The combined toxicity was completely blocked by
      MK801. To assess the specificity of the injury, we measured the diameter of cell
      nuclei in the organotypic culture stained with Hoechst 33342 because the nucleus
      shrinks when neurons are injured. These measurements showed that the combined
      toxin treatment selectively injured only the TH immunoreactive cells. Thus, in a
      model culture system where dopaminergic neurons innervate appropriate targets,
      excitotoxicity appears to be essential for the manifestation of the toxic actions
      of 6-hydroxydopamine, 1-methyl-4-phenylpyridinium and rotenone.

PMID- 15996476
TI  - Endovascular repair for concomitant multilevel aortic disease.
AB  - OBJECTIVE: Patients with multilevel aortic disease represent a small subgroup
      with the need for extensive surgical treatment at considerable risk. We present
      our experience of endovascular exclusion for simultaneous thoracic and abdominal
      aortic disease in four patients. METHODS: Between January 2002 and January 2005,
      four patients underwent endovascular repair for simultaneous thoracic and
      abdominal aortic disease. Mean age was 69+/-10 years (range, 60-81). Thoracic
      lesions included penetrating aortic ulcer (n=2, ruptured=1), atherosclerotic
      aneurysm (n=1), and chronic type B dissection (n=1). Abdominal aortic disease
      included atherosclerotic infrarenal (n=3) and juxtarenal (n=1) aortic aneurysms.
      Thoracic aortic stent-grafts had been the following: Excluder/TAG (n=3) or Talent
      (n=1) straight tube devices. Abdominal aortic stent-grafts used were as
      following: Excluder (n=3) or Zenith (n=1). All patients were followed-up with CT
      angiography and chest X-rays 1, 4, 12 months after the procedure, and once per
      year thereafter. RESULTS: Stent-graft deployment was technically successful in
      all cases. Intraoperative mortality was not observed. Mean procedure time was
      94+/-34 min (range, 70-145). Early postoperative complications occurred in one
      patient that developed acute renal failure but dialysis was not required. Mean
      hospitalisation was 8+/-5 days (range, 4-15). Late death occurred in one patient
      for an undetected ruptured thoracic type 1 endoleak. All three survivors are
      currently well 16.5 months (range, 3-36) after surgery. No neurological
      complications developed. CONCLUSION: Simultaneous abdominal and thoracic
      endovascular repair for multilevel aortic disease is feasible and could be a
      viable alternative in high-risk patients, who otherwise may not be suitable
      candidates for conventional repair.

PMID- 15996477
TI  - Reimplantation of the anomalous right coronary artery arising from the left
      coronary sinus: postoperative control using the multislice computed tomography
      (MSCT).

PMID- 15996478
TI  - Down-regulation of osteoprotegerin production in bone marrow macrophages by
      macrophage colony-stimulating factor.
AB  - Macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB
      ligand (RANKL) induce the differentiation of bone marrow macrophages (BMMs) into
      osteoclasts. To delineate mechanisms involved, the effect of M-CSF on the
      production of osteoprotegerin (OPG), decoy receptor of RANKL, in BMMs was
      investigated. Mouse bone marrow cells were cultured with M-CSF for 4 days and
      adherent cells formed were used as BMMs. BMMs were cultured with or without M
      CSF, and analyzed for expression of OPG and receptor activator of NF-kappaB
      (RANK; receptor for RANKL) mRNAs by real-time polymerase chain reaction and
      secretion of OPG by enzyme-linked immunosorbent assay. BMMs expressed macrophage
      markers, CD115 (c-fms), Mac-1 and F4/80, and showed phagocytotic activity. In
      addition, BMMs expressed OPG mRNA and secreted OPG into medium. M-CSF inhibited
      both the OPG mRNA expression and the OPG secretion dose-dependently and
      reversibly. The expression of RANK mRNA was not significantly affected by M-CSF.
      The results showed that M-CSF suppresses the OPG production in BMMs, which may
      increase the sensitivity of BMMs to RANKL.

PMID- 15996479
TI  - Granulocyte-macrophage colony-stimulating factor induces de novo methylation of
      the p15 CpG island in hematopoietic cells.
AB  - The process of p15 CpG island methylation induced by granulocyte-macrophage
      colony-stimulating factor (GM-CSF) was investigated, using MO7e cells. The cells
      proliferating in response to GM-CSF+fetal bovine serum (FBS) were almost fully
      methylated in the p15 CpG island. The withdrawal of both GM-CSF and FBS for 48 h
      reduced the cell viability, and increased the frequency of alleles with
      completely or partially demethylated CpG sites by approximately 50%. Viable cells
      were responsible for this epigenetic change. The add-back of GM-CSF restored the
      methylation. Seventy-two hours withdrawal of GM-CSF+FBS followed by 24-h exposure
      to inhibitors for DNA methyltransferase (DNMT) and histone deacetylase (HDAC)
      caused the demethylation of nearly all CpG sites in the p15 CpG island on every
      allele sequenced. When GM-CSF was re-added after 96-h treatment, the cells
      exhibited p15 transcriptional silencing via the methylation. The initial
      methylation event encompassed the entire CpG island. No new methylated alleles
      appeared in the coexistence of the DNMT and HDAC inhibitors. Taken together, GM
      CSF may be able to induce de novo methylation of the p15 gene, using HDAC(s) as
      well as DNMT(s).

PMID- 15996480
TI  - Humoral immune response and B-cell functions including immunoglobulin class
      switch are downregulated in aged mice and humans.
AB  - Vaccinations are powerful tools for combating infections. Because of the age
      related impairment in immune functions, the currently available vaccines are
      protecting only a small proportion of the elderly population. We, here, provide
      an overview of age-related changes in innate and adaptive immunity with
      particular emphasis to changes in antibody production with aging. We also
      summarize our results showing that the E2A-encoded transcription factor E47,
      which regulates many B cell functions including class switch recombination (CSR)
      and somatic hypermutation (SHM), is downregulated in splenic B cells from old
      mice. This leads to a reduction in the activation-induced cytidine deaminase
      (AID), which directly induces CSR and SHM, and, in turn, to reduced amounts of
      switched antibodies produced by splenic activated B cells. Our preliminary
      results in humans indicate similar reductions: we show herein that the expression
      of E2A and AID progressively decline with age. Our results provide a possible
      molecular basis for a decrease in the humoral immune response in aging mice and
      humans.

PMID- 15996481
TI  - A key role for Abl family kinases in EphA receptor-mediated growth cone collapse.
AB  - The ephrin-As, and their EphA receptor tyrosine kinases, guide retinal axons by
      contact-mediated repulsion to their correct target in the midbrain. We have
      developed a co-culture assay to observe the dynamic cytoskeletal rearrangements
      comprising retinal growth cone collapse stimulated by contact with an ephrin-A
      expressing fibroblast. We show that EphA-ephrin-A interaction at membrane contact
      sites triggers rapid loss of growth cone lamellipodia followed by axon retraction
      and cell-cell separation. Using this assay, in combination with soluble ephrin-A5
      induced growth cone collapse, we show that inhibiting the Rho effector, ROCK,
      prevents only ephrin-A-induced retinal axon retraction, but not loss of growth
      cone lamellipodia. This suggests that actin/myosin driven cell contraction alone
      does not mediate ephrin-A-induced repulsive responses. We provide evidence that
      Abl family kinases are a major effector of ephrin-A-induced retinal ganglion cell
      repulsion since the Abl inhibitor, STI571, prevents both loss of growth cone
      lamellipodia and axon retraction. These results comprise the first evidence that
      Abl family kinases play a role in EphA receptor-mediated axon guidance.

PMID- 15996482
TI  - Multiple signaling pathways regulate FGF-2-induced retinal ganglion cell neurite
      extension and growth cone guidance.
AB  - Growth cones use cues in their environment in order to grow in a directed fashion
      to their targets. In Xenopus laevis, fibroblast growth factors (FGFs) participate
      in retinal ganglion cell (RGC) axon guidance in vivo and in vitro. The main
      intracellular signaling cascades known to act downstream of the FGF receptor
      include the mitogen-activated protein kinase (MAPK), phospholipase Cgamma
      (PLCgamma) and phosphotidylinositol 3-kinase (PI3K) pathways. We used
      pharmacological inhibitors to identify the signaling cascade(s) responsible for
      FGF-2-stimulated RGC axon extension and chemorepulsion. The MAPK, PI3K and
      PLCgamma pathways were blocked by U0126, LY249002 and U73122, respectively. D609
      was used to test a role for the phosphotidylcholine-PLC (PC-PLC) pathway. We
      determined that the MAPK and two PLC pathways are required for FGF-2 to stimulate
      RGC neurite extension in vitro, but the response of axons to FGF-2 applied
      asymmetrically to the growth cone depended only on the PLC pathways.

PMID- 15996483
TI  - Muscarinic acetylcholine receptor activation enhances hippocampal neuron
      excitability and potentiates synaptically evoked Ca(2+) signals via
      phosphatidylinositol 4,5-bisphosphate depletion.
AB  - Using single cell Ca(2+) imaging and whole cell current clamp recordings, this
      study aimed to identify the signal transduction mechanisms involved in mACh
      receptor-mediated, enhanced synaptic signaling in primary cultures of hippocampal
      neurons. Activation of M(1) mACh receptors produced a 2.48 +/- 0.26-fold
      enhancement of Ca(2+) transients arising from spontaneous synaptic activity in
      hippocampal neurons. Combined imaging of spontaneous Ca(2+) signals with inositol
      1,4,5-trisphosphate (IP(3)) production in single neurons demonstrated that the
      methacholine (MCh)-mediated enhancement required activated G(q/11)alpha subunits
      and phospholipase C activity but did not require measurable increases in IP(3).
      Electrophysiological studies demonstrated that MCh treatment depolarized neurons
      from -64 +/- 3 to -45 +/- 3 mV and increased action potential generation.
      Depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2))
      enhanced neuronal excitability and prolonged the action of MCh. These studies
      suggest that, in addition to producing the second messengers IP(3) and
      diacylglycerol, mACh receptor activation may directly utilize PIP(2) hydrolysis
      to regulate neuronal excitability.

PMID- 15996484
TI  - Hormonal and body-size factors in relation to breast cancer risk: a prospective
      study of 11,889 women in a low-incidence area.
AB  - PURPOSE: This prospective cohort study of 11,889 women was conducted to determine
      significant factors associated with the risk of breast cancer among Chinese women
      in Taiwan, a low-incidence area. METHODS: In-person interviews were completed for
      subjects to solicit information on hormonal factors. Measurements of height,
      weight, and waist-and- hip circumferences were performed by well-trained
      assistants using standardized techniques. Cox proportional hazards models were
      employed to estimate relative risks (RRs) and 95% confidence intervals (CIs).
      RESULTS: During an average follow-up time of 10.3 years (range: 1 to 11 years)
      with an accumulation of 134,063 person-years, 104 incident breast cancer cases
      were identified through data linkage with national cancer registry profile. There
      was a significant elevation in breast-cancer risk with increasing duration of the
      interval between age at menarche and age at first full-term pregnancy (FFTP).
      Additionally, central adiposity reflected by hip circumference was a significant
      predictor of breast cancer in this Chinese female population. CONCLUSIONS: The
      findings of this study indicated common mechanisms responsible for the higher
      incidence of breast cancer in Western populations may also explain the risk of
      breast cancer development in Taiwan, a low-incidence area.

PMID- 15996485
TI  - A model of the hierarchy of behaviour, cognition, and consciousness.
AB  - Processes comparable in important respects to those underlying human conscious
      and non-conscious processing can be identified in a range of species and it is
      argued that these reflect evolutionary precursors of the human processes. A
      distinction is drawn between two types of processing: (1) stimulus-based and (2)
      higher-order. For 'higher-order,' in humans the operations of processing are
      themselves associated with conscious awareness. Conscious awareness sets the
      context for stimulus-based processing and its end-point is accessible to
      conscious awareness. However, the mechanics of the translation between stimulus
      and response proceeds without conscious control. The paper argues that higher
      order processing is an evolutionary addition to stimulus-based processing. The
      model's value is shown for gaining insight into a range of phenomena and their
      link with consciousness. These include brain damage, learning, memory,
      development, vision, emotion, motor control, reasoning, the voluntary versus
      involuntary debate, and mental disorder.

PMID- 15996486
TI  - Egocentrism, allocentrism, and Asperger syndrome.
AB  - In this paper, we attempt to make a distinction between egocentrism and
      allocentrism in social cognition, based on the distinction that is made in visuo
      spatial perception. We propose that it makes a difference to mentalizing whether
      the other person can be understood using an egocentric ("you") or an allocentric
      ("he/she/they") stance. Within an egocentric stance, the other person is
      represented in relation to the self. By contrast, within an allocentric stance,
      the existence or mental state of the other person needs to be represented as
      independent from the self. We suggest here that people with Asperger syndrome
      suffer from a disconnection between a strong naive egocentric stance and a highly
      abstract allocentric stance. We argue that the currently used distinction between
      first-person and third-person perspective-taking is orthogonal to the distinction
      between an egocentric and an allocentric stance and therefore cannot serve as a
      critical test of allocentrism.

PMID- 15996487
TI  - River drainages and phylogeography: an evolutionary significant lineage of shovel
      nosed salamander (Desmognathus marmoratus) in the southern Appalachians.

PMID- 15996488
TI  - Assessment of experimental osteoporosis using CT-scanning, quantitative X-ray
      analysis and impact test in calcium deficient ovariectomized rats.
AB  - INTRODUCTION: Osteoporosis is a major health problem in the elderly population
      particularly in postmenopausal women. Various techniques are currently available
      for detection and diagnosis of osteoporosis in humans, but not all of these can
      be used for evaluation of osteoporosis in animals. We assessed the feasibility
      and applicability of a spiral CT-scanning technique for use in evaluating bone
      loss in rats. In addition, we also tested the applicability of dispersive
      quantitative X-ray analysis (QXRA) coupled with scanning electron microscopy
      (SEM), and impact test to detect bone mineral content and biomechanical strength,
      respectively. METHODS: Twenty female Sprague Dawley rats were randomly assigned
      to sham operated or bilaterally ovariectomized groups and fed with a calcium
      deficient diet for 16 weeks. Femurs and tibias were collected at termination.
      Using a spiral CT-scanner various cortical bone morphometric indices were
      measured in femurs. SEM-QXRA was used to quantify the calcium to phosphorus ratio
      (Ca:P) in regions of high bone turnover both in sham and CD-OVX rats. Tibias were
      subjected to the impact test for evaluation of biomechanical strength. RESULTS:
      Compared to sham operated rats, the CD-OVX animals had decreased combined
      cortical thickness (CCT), cortical area (CA), cortical area/periosteal area and
      radial density (RD), with increased medullary width and cross sectional areas as
      determined by CT-Scanning technique. SEM-QXR analysis indicates a decreased Ca:P
      ratio in the metaphyseal regions of distal femurs in CD-OVX rats when compared to
      sham-operated rats. The results of the impact test demonstrate lower threshold
      energy in tibias of CD-OVX rats compared to sham operated rats. DISCUSSION: The
      ability of these techniques to distinguish the bone characteristics of sham
      operated rats from CD-OVX rats provides a methodological opportunity to assess
      osteoporosis in small animals like rats.

PMID- 15996489
TI  - Comparison of impact of EMCV replication on the nuclear apparatus of NIH 3T3 and
      HEp-2 cells.
AB  - We have investigated differences between the actions of encephalomyocarditis
      virus (EMCV) on cytometric indices in cultured NIH 3T3 and HEp-2 cells, which are
      characterized by different levels of transformation. HEp-2 cells surviving 48 h
      after EMCV infection showed lower nuclear ploidy, reduced nuclear area, fewer
      nucleoli and a higher percentage of euploid cells. There was a significant
      increase of nucleolar/nuclear DNA 6-24 h after EMCV infection. However, EMCV had
      markedly different effects on NIH 3T3 cells: there was a consistent increase in
      population ploidy, but the average number of nucleoli and the number of euploid
      cells in the population remained constant. The nucleolar/nuclear DNA ratio was
      almost unchanged. These different viral effects might be explained by the
      contrasting levels of differentiation of the cultured cell lines. The number of
      nucleoli does not depend on the amount of nuclear DNA in either viral-infected or
      intact cells but on the euploidy-to-aneuploidy ratio. The ratio of the sums of
      the nucleolar perimeters to the nuclear perimeter increases linearly with the
      number of nucleoli per nucleus in both intact and virus-infected cells. In both
      cell lines, the amount of DNA per nucleolus decreases as the number of nucleoli
      increases.

PMID- 15996490
TI  - Influence of membrane physical state on lysosomal potassium ion permeability.
AB  - Lysosomal permeability to potassium ions is an important property of the
      organelle. Influence of the membrane physical state on the potassium ion
      permeability of isolated lysosomes was assessed by measuring the membrane
      potential with bis(3-propyl-5-oxoisoxazol-4-yl)pentamethine oxonol and monitoring
      the lysosomal proton leakage with p-nitrophenol. The membrane fluidity of
      lysosomes was modulated by treatment with membrane fluidizer benzyl alcohol and
      rigidifier cholesteryl hemisuccinate. Changes in the membrane order were examined
      by steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene. The
      measurements of membrane potential and proton leakage demonstrated that the
      permeability of lysosomes to potassium ions increased with rigidification of
      their membranes by cholesteryl hemisuccinate treatment at 37 degrees C, and
      decreased with fluidization of their membranes by benzyl alcohol treatment at 2
      degrees C. The changes in ion permeability could be recovered by fluidizing the
      rigidified membranes and rigidifying the fluidized membranes. The results suggest
      that the physical states of lysosomal membranes play an important role in the
      regulation of their K(+) permeability.

PMID- 15996491
TI  - Centrosome aberrations in hematological malignancies.
AB  - As the primary microtubule organizing center of most eukaryotic cells,
      centrosomes play a fundamental role in proper formation of the mitotic spindle
      and subsequent chromosome separation. Normally, the single centrosome of a G1
      cell duplicates precisely once prior to mitosis in a process that is intimately
      linked to the cell division cycle via cyclin-dependent kinase (cdk) 2 activity
      that couples centrosome duplication to the onset of DNA replication at the G1/S
      transition. Accurate control of centrosome duplication is critical for symmetric
      mitotic spindle formation and thereby contributes to the maintenance of genome
      integrity. Numerical and structural centrosome abnormalities are hallmarks of
      almost all solid tumors and have been implicated in the generation of multipolar
      mitoses and chromosomal instability. In addition to solid neoplasias, centrosome
      aberrations have recently been described in several different hematological
      malignancies like acute myeloid leukemias, myelodysplastic syndromes, Hodgkin's
      as well as non-Hodgkin's lymphomas, chronic lymphocytic leukemias and multiple
      myelomas. In analogy to many solid tumors a correlation between centrosome
      abnormalities on the one hand and karyotype aberrations as well as clinical
      aggressiveness on the other hand seems to exist in myeloid malignancies, chronic
      lymphocytic leukemias and at least some types of non-Hodgkin's lymphomas.
      Molecular mechanisms responsible for the development of centrosome aberrations
      are just beginning to be unraveled. In general, two models with distinct
      functional consequences can be envisioned. First, centrosome aberrations can
      arise as a consequence of abortive mitotic events and impaired cytokinesis.
      Second, evidence has been provided that centrosome amplification can also precede
      genomic instability and arise in normal, diploid cells. Accordingly, this review
      will focus on recent advances in the understanding of both, causes and
      consequences of centrosome aberrations in hematological malignancies.

PMID- 15996492
TI  - Epidemiology of dog bites: a Belgian experience of canine behaviour and public
      health concerns.
AB  - This paper reviews three studies that have been conducted in Belgium on dog bites
      on children. (1) A telephone study revealed that 22/1000 children <15 years of
      age were victims of dog bites annually. (2) Data on the characteristics of dog
      bites were collected prospectively over a period of 8.5 months in six hospital
      emergency departments. "Dangerous dogs" were not responsible for the majority of
      the accidents. In 67/100, incidents documented, the bites appeared to be
      triggered by an interaction of the child. Education appeared to be the preventive
      measure with the highest priority. (3) Among 22 child victims of dog bites, 12
      had symptoms of post-traumatic stress disorders some seven months following the
      accident. Based on these local studies, several initiatives have been undertaken
      to favour both primary and secondary prevention measures. An appropriate
      psychological preventive intervention should be offered to all victims of dog
      bites.

PMID- 15996493
TI  - Effect of a single injection of progesterone on ovarian follicular cysts in
      lactating dairy cows.
AB  - The objective of this experiment was to evaluate the effect of a single injection
      of progesterone on the lifespan of ovarian follicular cysts and to examine the
      fate of follicles that mature following treatment. Lactating Holstein and Jersey
      cows with ovarian follicular cysts were identified by rectal palpation. The
      ovaries of cystic cows were then examined by transrectal ultrasonography three
      times weekly to monitor formation of new follicular cysts. Cows with newly formed
      follicular cysts were treated either with a single injection of progesterone (200
      mg, IM, n = 11) or corn oil vehicle (n = 7). Venous blood samples were collected
      daily for quantification of progesterone. Blood sampling and ultrasonography
      continued until ovulation or a new follicular cyst formed. Treatment reduced the
      lifespan of the cyst by 12 days, from 29.8 +/- 2.3 days in control cows to 17.2
      +/- 1.8 days in progesterone-treated cows (P = 0.01). Progesterone treatment also
      tended to alter the frequency of subsequent follicular events. Ovulation occurred
      in 4/11 cows that were treated with progesterone whereas none of the vehicle
      treated cows ovulated (P = 0.07). In conclusion, a single injection of 200mg of
      progesterone, administered early in the life of an ovarian follicular cyst,
      shortened its lifespan and in some cases was followed by ovulation of a new
      follicle.

PMID- 15996494
TI  - Septicaemia secondary to infection by Corynebacterium macginleyi in an Indian
      python (Python molurus).
AB  - A seven-year-old female Indian python (Python molurus) weighing about 35kg was
      euthanased after several clinical episodes of stomatitis, pneumonia, ophthalmitis
      and dystocia over a period of four years. The animal had been maintained in a
      terrarium in a circus truck at an adequate temperature. During shows, however,
      the snake was considered to be exposed to stressful conditions for several hours
      at a time at low temperatures and with noise and bright lights. A post-mortem
      examination indicated ulcerative stomatitis, osteomyelitis, severe pneumonia and
      numerous granulomata and multifocal necrosis in stomach and spleen.
      Corynebacterium macginleyi was isolated in pure culture from the ulcerative
      stomatitis, and mixed with Stenotrophomonas maltophilia from the lungs and
      spleen. The findings indicated that the snake had died from a septicaemic process
      caused by C. macginleyi, probably originating from the stomatitis. The role of S.
      maltophilia as a secondary agent is discussed. The stress of the circus show and
      poor husbandry may have predisposed the animal to infection and septicaemia. This
      is the first report of C. macginleyi causing disease in a snake.

PMID- 15996495
TI  - Adiponectin and leptin are related to fat mass in horses.
AB  - Plasma concentrations of adiponectin and leptin were measured in 23 mature
      Standardbred mares (age: 10+/-3 years) and 12 weanling fillies (10 Quarter
      Horse/Belgian crossbreds and two Quarter Horses; aged: 4+/-3 months) to test the
      hypothesis that adipocytokines are proportional to adiposity in horses. Rump fat
      thickness was measured using B-mode ultrasound and percent body fat (% fat)
      calculated using a published formula for the estimation of fatness in horses.
      Plasma adiponectin and leptin were determined using radioimmunoassay. In the
      absence of purified equine adiponectin or leptin, results were expressed as human
      equivalents (HE) of immunoreactive (ir) adipocytokines. Plasma ir-leptin HE
      concentration was positively correlated (r=0.543; P<0.001) with percent body fat
      and (r=0.556; P<0.001) to fat mass in all horses. The plasma ir-leptin HE
      concentration was lower (P=0.03) in weanlings (1.90+/-0.34 ng/mL HE) than in
      mature mares (3.47+/-0.50 ng/mL HE). The ratio of ir-adiponectin HE to ir-leptin
      HE was negatively correlated (r=-0.621; P<0.001) to percent fat and (r=-631;
      P<0.001) to fat mass in all horses. The ratio of ir-adiponectin HE to ir-leptin
      HE was higher (P<0.001) in weanlings (3.04+/-0.51) than mature mares (1.03+/
      0.13). These data suggest that leptin is proportional while adiponectin is
      inversely proportional to adiposity in horses.

PMID- 15996496
TI  - Temperature dependence of the 1H chemical shift of tetramethylsilane in
      chloroform, methanol, and dimethylsulfoxide.
AB  - The chemical shift of tetramethylsilane (TMS) is usually taken to be zero.
      However, it does vary slightly with temperature, having obvious implications for
      studies of temperature effects on chemical shifts. In this work, we measure the
      variation in the chemical shift of TMS with temperature in three solvents, CDCl3,
      CD3OD, and DMSO-d6, relative to the resonant frequency of 3He gas, which can be
      reasonably assumed to be temperature independent. In all three solvents, the
      average temperature coefficient over a wide temperature range is about -6 x 10(
      4) ppm/degrees C, a factor of five smaller than that previously reported in the
      literature. Data are included for 3He resonance frequencies over a temperature
      range of -110 to +180 degrees C, along with new measurements of volume magnetic
      susceptibilities of the three solvents and estimates of their temperature
      dependence. A novel method is used to provide temperature measurement via 2H
      resonances of methanol and ethylene glycol samples, which can concurrently be
      used for field/frequency locking.

PMID- 15996497
TI  - The functional morphology of the english sparrow cecum.
AB  - As birds do not have a urinary bladder, the kidneys and lower gastrointestinal
      tract must function in concert to maintain fluid and electrolyte homeostasis. In
      birds, urine is conveyed to the cloaca, and moved by reverse peristalsis into the
      colon and digestive ceca. Digestive ceca have been well studied for non-passerine
      birds and have been shown to absorb substrates and water. The ceca of passerine
      birds have been suggested to be non-functional because of their small size. The
      present study was undertaken to examine the morphology and cytochemistry of the
      small ceca of the English sparrow (Passer domesticus). Three-dimensional
      reconstruction of the ceca from serially sectioned tissue showed these organs to
      have a central channel with a large number of side channels. Electron micrographs
      indicated that all of the channels are lined by epithelial cells with a very
      dense microvillus brush border as well as a region densely packed with
      mitochondria just below the brush border. Specific staining for Na(+), K(+)
      ATPase indicated the enzyme to be localized to the brush border. Quantification
      of Na(+), K(+)-ATPase activity showed it to be comparable to the coprodeum of
      domestic fowl. The data suggest that the small ceca of passerine birds may
      function in fluid and electrolyte homeostasis.

PMID- 15996498
TI  - Alternative DNA-based newborn screening for glucose-6-phosphate dehydrogenase
      deficiency.
AB  - Newborn screening for G6PD deficiency has been carried out in several countries
      for more than 25 years. A semi-quantitative enzymatic assay has been used in most
      laboratories, however, heat inactivation during the summer can cause a
      significant increase in the false positive rate for this assay. We have developed
      an alternative DNA-based newborn screening assay for the detection of common
      mutations within the G6PD gene. The panel of mutations includes the common
      African A- mutation (G202A;A376G), the common Mediterranean mutation (C563T), and
      two common Chinese mutations (G1376T and G1388A). A parallel study was performed
      through screening a total of 4245 neonatal specimens using both the enzymatic and
      the DNA-based assays. In this population, 49 newborns were identified as
      hemizygous or homozygous for the A- mutation with an average enzyme activity of
      59 microM, 323 were identified as a carrier or unaffected with an average enzyme
      activity of 208 microM, and no mutation was detected for the remaining 3873
      specimens with an average enzyme activity of 234 microM. With this panel of
      mutations, more than 90% of all affected infants can be identified in our
      population.

PMID- 15996499
TI  - Commentary on Vrabelova et al.
AB  - The paper by Vrabelova et al. reflects a comprehensive genetic approach in
      characterizing genetically patients with Wilson disease (WD). They studied
      mutations within ATP7B-the gene encoding the defective WD protein ATPase 7B-in
      227 WD patients from 200 unrelated Czech and Slovak families, which represents a
      very large cohort for WD, and therefore, the impact of their findings are highly
      important. There are accumulating papers published on mutations in WD, but
      besides reporting new mutations, mostly the genetic analysis is presented by
      sequencing data of limited exon analysis and the lack of additional screening
      techniques used. This in turn complicates the current interpretation of the
      reported mutations within ATP7B and the role of genetic testing for WD in
      general. The real distribution of mutations within ATP7B are not well
      established, there is limited information on the mutational detection rate, and
      there is still little known on the promoter region of ATP7B.

PMID- 15996500
TI  - Total hip arthroplasty: how much physical activity is too much?

PMID- 15996501
TI  - The preclinical phase of rheumatoid arthritis and lupus.

PMID- 15996502
TI  - Osteoporosis treatment in postmenopausal women after peripheral fractures: impact
      of information to general practitioners.
AB  - A low-impact fracture in a postmenopausal woman should prompt investigations for
      osteoporosis followed, if needed, by appropriate treatment. OBJECTIVES: To
      evaluate the impact of information alerting general practitioners to the need for
      osteoporosis treatment in postmenopausal women with a recent history of
      peripheral fracture. METHODS: We conducted a prospective 7-month follow-up study
      of 78 postmenopausal women, with a mean age of 81.5 years, admitted to the
      emergency department for peripheral fractures. Three months after the fracture,
      we sent a letter to the general practitioner of each patient emphasizing the
      probable contribution of osteoporosis to the fracture and the need for
      osteoporosis treatment. Six months after the fracture, we interviewed the
      patients by telephone, and one month later we mailed a questionnaire to those
      physicians who had not followed the treatment recommendation. RESULTS: At
      emergency room admission, 9 patients were receiving treatment for osteoporosis
      (hormone replacement therapy in one patient and calcium and vitamin D
      supplementation in eight patients). Admission to a ward was required in 66 (85%)
      patients. No treatment for osteoporosis was given at discharge. Six months after
      discharge, seven patients reported recent initiation of calcium and vitamin D
      supplementation, and none reported other osteoporosis treatments. The response
      rate to the physician questionnaire mailed 7 months after discharge was 54%
      (n=28); responses showed treatment of 11 additional patients, by calcium and
      vitamin D supplementation in six cases and by bisphosphonates with or without
      calcium and vitamin D supplementation in five cases. Treatment initiation rates
      were similar in patients younger and older than 80 years. CONCLUSIONS: Despite
      information of general practitioners about the need for osteoporosis treatment,
      such treatment was initiated in only 30.5% of patients. General practitioners may
      be reluctant to initiate osteoporosis treatment in patients who are very old or
      have multiple comorbidities.

PMID- 15996503
TI  - Measuring enthesitis in ankylosing spondylitis.

PMID- 15996504
TI  - Impact of medical practices on the costs of management of rheumatoid arthritis by
      anti-TNFalpha biological therapy in France.
AB  - When the anti-TNFalpha drugs first came onto the market, their high price was the
      subject of much debate. Moreover, we must add the costs associated with their
      administration to the purchase price. Variations in medical practices may be the
      source of substantial variations in these costs. OBJECTIVE: To compare the costs
      involved with the use of infliximab and etanercept in the treatment of rheumatoid
      arthritis (RA) and to study the impact of variations in medical practices on
      them. METHODS: A pragmatic cost minimization analysis was conducted from the
      payer's perspective to compare the costs of administration, that is, the direct
      medical costs, of the first two available anti-TNFalpha agents: infliximab and
      etanercept. Records of 60 patients from three university hospital rheumatology
      departments were reviewed retrospectively for a 52-week period. This analysis
      considered the following costs: purchase costs for the drugs and for any co
      prescribed disease-modifying drugs, inpatient or outpatient administration,
      medical follow-up and the transportation costs associated with treatment that
      were reimbursed by the French health insurance system. Costs that did not differ
      between the two products were excluded (work-up for inclusion, etc.). RESULTS:
      Data were collected for 58 patients, 30 treated with infliximab and 28 with
      etanercept. Patients' mean age was 52 years; 81% were women. RA had first
      developed on average 15 years earlier; the disease was positive for rheumatoid
      factors in 68% of cases and erosive in 93%. The total average annual cost of
      administration did not differ for infliximab and etanercept: 19,469 and 19,619 ,
      respectively (P=0.56). The mean costs of administration nonetheless varied
      considerably between the three hospital centers: from 16,566 to 24,313 for
      infliximab (P<0.0001) and from 16,069 to 24,383 for etanercept (P<0.0001).
      CONCLUSION: The financial burden of biological treatments for RA is strongly
      influenced by the substantial heterogeneity in medical practices.

PMID- 15996505
TI  - Evolution of an 1 MHz ultrasonic cavitation bubble field in a chopped irradiation
      mode.
AB  - In this paper the evolution of an ultrasonic cavitation bubble field is studied
      by means of the void rate, the cavitation noise power and the electric power that
      feeds the ultrasonic transducer. The ultrasonic irradiation is performed in
      chopped mode. It is observed two kinds of evolution that differ respectively by a
      slow (A regime) and a fast (B regime) void rate increase. They correspond to
      cavitation regimes that are identified as respectively a stable cavitation and an
      inertial cavitation field. The beginning of the fast increase of the void rate is
      delayed from the irradiation start and this delay depends on the chopping
      frequency of the irradiation mode.

PMID- 15996506
TI  - Thrombospondin 1, thrombospondin 2 and the eye.
AB  - Thrombospondin 1 and thrombospondin 2 (TSP1 and TSP2), which comprise the
      subgroup A thrombospondins, are matricellular proteins. As matricellular
      proteins, they modulate interactions between cells and the cellular environment,
      regulate cell adhesion and typically are expressed during tissue formative
      processes. In general, TSP1 and TSP2 counter angiogenesis (including tumour
      angiogenesis) and play important but contrasting roles during cutaneous repair.
      The two proteins are involved in development, including that of the eye, although
      evidence suggests that they have their greatest impact during tissue production
      in the adult. In the normal adult eye, they tend to be found at sites of ongoing
      matrix synthesis or cell-matrix interactions. At these sites, the two proteins
      possibly influence cellular differentiation and/or basement membrane deposition.
      TSP1 is also present in the intraocular fluids and drainage pathway, where it may
      function in maintaining the anti-angiogenic environment and in intraocular
      pressure control, respectively. TSP1 could also be involved in ocular immune
      privilege. Unlike in skin wounds, where TSP1 is derived from the blood and is
      present only in the early phases of repair, ocular tissue damage appears to lead
      to protacted TSP1 synthesis by local cells. This response might help suppress
      angiogenesis in the transparent tissues of the eye and so lessen visual axis
      opacification following injury. However, TSP2, which is also produced by damaged
      ophthalmic tissue and may be especially important in matrix organisation, seems
      to augment contraction in anomalous intraocular fibrosis. Elucidating the roles
      of TSP1 and TSP2 in ocular physiology and pathobiology may lead to improved
      therapies for neovascular, neoplastic, reparative and other ophthalmic diseases.

PMID- 15996507
TI  - The arms race continues: battle strategies between plants and fungal pathogens.
AB  - Plants are under constant attack by a vast array of pathogens. To impede their
      attackers they use both broad-spectrum and pathogen-specific defence mechanisms.
      The arms race between plants and fungal pathogens is fascinatingly varied, and
      what might be elicited as a plant defence mechanism against a pathogen could
      promote or enhance the virulence of other pathogens. Fungi use countermeasures to
      detoxify plant antimicrobial compounds and to evade host resistance mechanisms.
      Certain fungal species also manipulate the host hormone balance to create an
      environment that is beneficial to their survival. Several lines of evidence
      indicate a co-evolutionary arms race in which both plants and fungi can respond
      to changes that occur in their opponents.

PMID- 15996508
TI  - Pneumocystis: not just pneumonia.
AB  - Once known exclusively as the agents of severe pneumonia in immunocompromised
      individuals, Pneumocystis spp. are now being associated with asymptomatic
      carriage in hosts that do not have profound immune debilitation. In the absence
      of a cultivation system, polymerase chain reaction and histological studies have
      identified Pneumocystis in neonatal populations, in pregnant women and in other
      patients that have chronic underlying disease processes. These findings in humans
      and in experimental animal models indicate the presence of potential reservoirs
      of infection, and provide insights into the transmission of this fungus. Also,
      the role of Pneumocystis has been investigated as a possible co-morbidity factor.

PMID- 15996509
TI  - Detection of numerical chromosomal aberrations by flow cytometry: a novel process
      for identifying aneugenic agents.
AB  - Aneuploidy plays a significant role in adverse human health conditions including
      birth defects, pregnancy wastage, and cancer. Currently, there is no screening
      method sufficiently validated that can be used routinely to identify aneugenic
      agents in vitro because most conventional test systems rely on the labor
      intensive microscopic assessment of the aneuploid cell population. Our laboratory
      has recently developed a flow cytometry-based procedure for assessing numerical
      chromosomal aberrations in mitotic populations of lymphocytes on the basis of DNA
      content. Studies were conducted in 24 h treated human lymphocyte cultures to
      determine the sensitivity of this flow cytometry-based procedure to detect
      aneugenic agents. A comparison between the microscopic and the flow cytometry
      based procedures for scoring polyploidy shows a strong agreement exists between
      the two methods. Treatments with two known aneugenic agents, griseofulvin, and
      paclitaxel (taxol), resulted in a dose-related increase in the mitotic index,
      aneuploidy, and polyploidy. In contrast, results from the treatments with two
      known clastogenic agents, mitomycin-C, and etoposide, show a dose-related
      decrease in the mitotic index with a slight increase in the frequency of
      hypodiploidy at concentrations that produce severe chromosomal breakage. There
      were no increases in hyperdiploidy and polyploidy observed. In conclusion, the
      reproducibility of the results obtained in this study indicates that this flow
      cytometry-based procedure for assessing numerical chromosomal effects in mitotic
      populations on the basis of DNA content is promising for the routine detection
      and characterization of aneugenic agents.

PMID- 15996510
TI  - Reducing-difference infrared spectral analysis of cis- and trans-configurated
      lactams.
AB  - The conventional (non-polarized) and linear-polarized IR-spectra of 2-pyrrolidone
      and laurolactam as typical representatives of lactams with cis- and trans-amide
      configuration, respectively, were studied by means of difference IR-spectroscopy.
      The application of this method to treatment of the non-polarized IR-spectra
      permits additional conclusions about the likely self-associates of these
      compounds dissolved in aprotic solvents. By means of the difference linear
      dichroic IR-spectroscopy, a more precise assignment of the characteristic bands
      of the lactam cis- and trans-peptide forms as well as their stereo structures
      were accomplished. A comparative analysis with the linear-dichroic IR-spectra of
      epsilon-caprolactam and caprylolactam, as similar compounds, with cis- and trans
      conformation, respectively, was also carried out.

PMID- 15996512
TI  - Synthesis and spectroscopic study of copper(II) and manganese(II) complexes with
      pipemidic acid.
AB  - The interaction of copper(II) and manganese(II) with pipemidic acid, Hpipem,
      afforded the complexes [Cu(pipem)(2)(H(2)O)] x 2H(2)O, 1 and
      [Mn(pipem)(2)(H(2)O)], 2. The new complexes have been characterised by elemental
      analyses, infrared, UV-vis and X-band EPR spectroscopy in the temperature range
      from 4 to 300 K. The monoanion, pipem, exhibits O,O ligation through the carbonyl
      and carboxylato oxygen atoms. Five coordinate square-pyramid configuration has
      been proposed for 1 and 2, and the fifth apical position is occupied by a
      coordinated water molecule.

PMID- 15996511
TI  - Synthesis, characterization and thermal behavior of 4-chloromethyl-2-(2
      hydroxybenzilidenehydrazino) thiazole and its complexes with Cr(III), Co(II),
      Ni(II) and Cu(II).
AB  - A new ligand, 4-chloromethyl-2-(2-hydroxybenzilidenehydrazino) thiazole, has been
      synthesized from dicholoroacetone and 2-hydroxybenzylidenethiosemicarbazon. Metal
      complexes of the ligand were prepared from acetate salts of Co(II), Cu(II),
      Ni(II) and chloride of Cr(III) in dry acetone. Characterization of the ligand and
      its complexes was made by microanalyses, FT-IR, 13C, 1H NMR and UV-vis
      spectroscopy, magnetic susceptibility and thermogravimetric analysis. In the
      light of these results, it was suggested that two ligands coordinate to each
      metal atom by hydroxyl oxygen, imino nitrogen and thiazole ring nitrogen to form
      high spin octahedral complexes with Cr(III), Co(II), Ni(II) and Cu(II).

PMID- 15996513
TI  - High selective determination iron(II) by its enhancement effect on the
      fluorescence of pyrene-tetramethylpiperidinyl (TEMPO) as a spin fluorescence
      probe.
AB  - A novel fluorescence method determination for iron(II) with a high selectivity
      and sensitivity has been proposed, based on the enhancement of fluorescence
      signals resulting from specific redox reaction between synthesized spin
      fluorescence probe pyrene-tetramethylpiperidinyl (TEMPO) and iron(II). Under the
      experimental conditions, fluorescent probe displayed a rapid and linear response
      for iron(II) over the concentration range from 2.4 x 10(-7) to 3.6 x 10(-6)
      mol/L. The limit of detection was 4.0 x 10(-8) mol/L. The relative standard
      deviation of six replicate measurements was 1.90% for 3.0 x 10(-7) mol/L
      iron(II). Because of the specific redox reaction between developed spin
      fluorescence probe and iron(II), there are few interference by other ions,
      especially in the presence of relative high concentration iron(III). The method
      has been successfully applied for iron(II) determinations in two different kinds
      of real samples. Results determined by the proposed method agree favorably with
      those determined UV-vis spectrometry method with 1,10-phenanthroline.

PMID- 15996514
TI  - Vibrational assignment, structure and intramolecular hydrogen bond of 4
      methylamino-3-penten-2-one.
AB  - The molecular structure, intramolecular hydrogen and vibrational frequencies of 4
      methylamino-3-penten-2-one were investigated by a series of density functional
      theoretical (DFT) calculations and ab initio calculation at the post-Hartree-Fock
      (MP2) level. Fourier transform infrared and Fourier transform Raman spectra of
      this compound and its deuterated analogue were clearly assigned. The calculated
      geometrical parameters show a strong intramolecular hydrogen bond with a N...O
      distance of 2.622-2.670 A. This bond length is about 0.02 A shorter than that in
      its parent, 4-amino-3- penten-2-one which is in agreement with spectroscopic
      results. Furthermore, the conformations of methyl groups with respect to the
      plane of the molecule and with respect to each other were investigated.

PMID- 15996515
TI  - Impact of clinical information-retrieval technology on physicians: a literature
      review of quantitative, qualitative and mixed methods studies.
AB  - PURPOSE: This paper appraises empirical studies examining the impact of clinical
      information-retrieval technology on physicians and medical students. METHODS: The
      world literature was reviewed up to February 2004. Two reviewers independently
      identified studies by scrutinising 3368 and 3249 references from bibliographic
      databases. Additional studies were retrieved by hand searches, and by searching
      ISI Web of Science for citations of articles. Six hundred and five paper-based
      articles were assessed for relevance. Of those, 40 (6.6%) were independently
      appraised by two reviewers for relevance and methodological quality. These
      articles were quantitative, qualitative or of mixed methods, and 26 (4.3%) were
      retained for further analysis. For each retained article, two teams used content
      analysis to review extracted textual material (quantitative results and
      qualitative findings). RESULTS: Observational studies suggest that nearly one
      third of searches using information-retrieval technology may have a positive
      impact on physicians. Two experimental and three laboratory studies do not reach
      consensus in support of a greater impact of this technology compared with other
      sources of information, notably printed educational material. Clinical
      information-retrieval technology may affect physicians, and further research is
      needed to examine its impact in everyday practice.

PMID- 15996516
TI  - Comparison of CD-Rom and Internet access to clinical information.
AB  - INTRODUCTION: The New Zealand National Poisons Centre has developed an extensive
      clinical poisons information database, TOXINZ. This resource was originally
      provided on a CD-Rom, and in 2002 made accessible solely via the Internet
      (www.toxinz.com). It was unknown whether users would prefer the CD-Rom or
      Internet version to access the same information. METHODS: In September 2003 a
      total of 100 questionnaires were mailed to the emergency departments of 15
      hospitals to be answered by medical and nursing staff utilizing the Internet
      version of TOXINZ. The results were then compared with a nearly identical
      questionnaire conducted in the same way in the same hospitals when only the CD
      Rom database version was available. RESULTS: There was a 79% response rate with
      both medical and nursing staff rating the poisons management recommendations
      highly when accessed both on CD-Rom and Internet. Statistically significant
      differences (p<0.05, Mann-Whitney U-test) identified the Internet accessed
      database as: supplying better visual aids, being more repetitive, harder to
      search, and more difficult to print. CONCLUSION: Those developing Internet
      accessible databases for a healthcare environment are encouraged to incorporate
      robust search functionality, mobility solutions, and an ability to integrate with
      other healthcare applications.

PMID- 15996517
TI  - Common variable immunodeficiency: the immune system in chaos.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous disorder that is
      associated with low serum-immunoglobulin concentrations, defective specific
      antibody production and an increased susceptibility to bacterial infections of
      the respiratory and gastrointestinal tracts. In spite of the identification of
      genes that are associated with several known primary immunodeficiencies, the
      basic immunologic and molecular defects of the majority of patients with CVID
      have remained obscure. Most of the studies aimed at understanding the
      immunopathogenesis of CVID suggest that this condition is primarily a T-cell
      disorder, although renewed attention on the genetic linkage and haplotype
      analysis in families of patients with CVID and on the role of dendritic cells and
      B cells has revealed several interesting features. This new information should
      assist in understanding the pathogenesis of CVID and improving the therapeutic
      strategies.

PMID- 15996518
TI  - The gene family of ABC transporters--novel mutations, new phenotypes.
AB  - Members of the ABC (ATP-binding cassette) superfamily of genes encode
      transmembrane proteins that are involved in the transport of a variety of
      substrates both in and out of the cells, in addition to across intracellular
      membranes. Recently, mutations in two ABC-transporter genes, ABCC6 and ABCA12,
      have been demonstrated to underlie phenotypically different diseases affecting
      the skin (pseudoxanthoma elasticum and harlequin ichthyosis, respectively),
      attesting to the spectrum of ABC gene mutations in human diseases. These findings
      have a major impact on the molecular genetics of these devastating disorders in
      terms of DNA-based prenatal testing and pre-implantation genetic diagnosis.

PMID- 15996519
TI  - Inhibitors of efflux pumps in Gram-negative bacteria.
AB  - In Gram-negative bacteria, efflux complexes, consisting of an inner-membrane
      pump, a periplasmic adaptor protein and outer-membrane channel, provide an
      efficient means for the export of structurally unrelated drugs, causing the
      multidrug-resistance phenotype. Resistance due to this antibiotic efflux is an
      increasing problem worldwide. A new molecular challenge is to combat this
      transport by searching for new molecules to block efflux and thus restore drug
      susceptibility to resistant clinical strains. Recent data shed new light on the
      structure and activity of the archetypal efflux pumps AcrAB-TolC and MexAB-OprM.
      Here, we describe recent insights into the molecular mechanisms of bacterial
      efflux pumps and their inhibitors. Current progress for the clinical use of
      efflux-pump inhibitors and new strategies to combat the drug-efflux mechanisms
      will be discussed.

PMID- 15996520
TI  - AAV2/5 vector expressing galactocerebrosidase ameliorates CNS disease in the
      murine model of globoid-cell leukodystrophy more efficiently than AAV2.
AB  - Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage
      disorder caused by mutations in the galactosylceramidase (GALC) gene. Infantile
      GLD has a lethal course with severe cerebral demyelination that progresses to
      death by 2 years of age. In the current study twitcher mice, an authentic murine
      model of infantile GLD, were given intracranial injections of either recombinant
      adeno-associated virus serotype 2 encoding the murine Galc cDNA (AAV2-GALC) or
      the same genome pseudotyped with AAV5 capsid proteins (AAV2/5-GALC) on day 3 of
      age. The group injected intracranially with AAV2/5-GALC had approximately 25-fold
      greater than normal Galc levels in the brain, while AAV2-GALC-injected animals
      had 28% normal levels. The average life expectancy of twitcher mice (
      approximately 38 days) was significantly (P < 0.0001) increased to 48 and 52 days
      for the AAV2-GALC- and AAV2/5-GALC-treated groups, respectively. The AAV2/5-GALC
      group performed significantly better in a battery of behavioral tests compared to
      untreated, AAV2-GFP-treated, or AAV2-treated twitcher animals. This longitudinal
      study demonstrated that AAV2/5-GALC-mediated gene therapy resulted in higher
      levels of Galc expression and slowed the neurologic deterioration more completely
      than AAV2-GALC in the murine model of globoid-cell leukodystrophy. However, the
      clinical improvements, as assessed by behavioral tests and life span, were only
      modest.

PMID- 15996521
TI  - Spontaneous echo contrast of unexpected etiology.
AB  - Cor triatriatum sinister is a rare congenital anomaly characterized by the
      presence of a fibromuscular membrane dividing the left atrium into two chambers:
      one entering the four pulmonary veins, the other connecting to the mitral valve.
      The extent of the communication between the two chambers and the presence of
      associated lesions determine the severity of symptoms and the complications. We
      report the case of a 20-year-old man firstly diagnosed with obstructive cor
      triatriatum sinister and severe pulmonary hypertension.

PMID- 15996522
TI  - RETRACTED: Age dependency in the timing of mitral annular motion in relation to
      ventricular filling in healthy subjects - A pulsed and tissue Doppler study.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see .The Publisher apologizes for any inconvenience this may
      cause.

PMID- 15996523
TI  - Caught in the act: serial, real time images of a thrombus traversing from the
      right to left atrium across a patent foramen ovale.
AB  - AIMS: To illustrate the association between a patent foramen ovale (PFO) and
      paradoxical embolization. METHODS AND RESULTS: We report a unique case of a
      paradoxical embolization across a PFO noted during a transesophageal
      echocardiographic study. Serial images demonstrate the thrombus migrating from
      the superior vena cava to the left atrium across the PFO. CONCLUSIONS: This case
      establishes the association between the PFO and paradoxical embolism
      unequivocally.

PMID- 15996524
TI  - Doppler derived coronary flow reserve during dobutamine stress echocardiography
      further improves detection of myocardial ischemia.
AB  - BACKGROUND: The coronary flow velocity (CFV) has been used to estimate coronary
      flow reserve (CFR) during dobutamine stress echocardiography (DSE). However, the
      relationship of the CFR to myocardial wall thickening (WT) has not been
      investigated. OBJECTIVES: The aims of this study were: (1) to assess the
      feasibility of obtaining systolic and diastolic CFV and thus CFR during DSE and
      (2) to assess the relation between CFR and stress induced WT. METHODS: Distal
      left anterior descending CFV was recorded by transthoracic Doppler
      echocardiography during DSE. Systolic and diastolic velocities were measured at
      rest, low and peak dobutamine doses, simultaneously, WT of distal anteroseptal
      segment was assessed by 2D-guided M-mode. The CFV and CFR of patients with normal
      WT defined as thickening of >50% (group 1) at peak stress were compared to that
      of patients with abnormal WT (group 2). RESULTS: A total of 67 patients, 34
      females and 33 males (mean age of 66.5+/-14.5 years) were studied. The
      feasibility of assessing the CFR was 97% from peak diastolic velocity, 91% from
      diastolic time velocity integral, 91% from peak systolic velocity, and 90% from
      systolic time velocity integral. Contrast agent was used in 6 patients (7%) to
      obtain the CFV. Twenty-five of 67 patients demonstrated abnormal wall thickening.
      The percentage of WT was 30.9+/-15.7% in group 2 compared to 80.8+/-24.3% in
      group 1 (p<0.0001). The 25 patients in group 2, who developed abnormal WT,
      demonstrated significantly lower CFR at low dose, as well as at peak dobutamine
      dose compared to patients in group 1 (1.55+/-0.5 vs. 2.03+/-0.6, p<0.008).
      CONCLUSION: CFV and CFR assessments are feasible during DSE with second harmonic
      imaging in most patients without use of contrast agent. CFR assessment during DSE
      correlates well with wall thickening and was able to detect ischemia early before
      development of wall motion abnormality.

PMID- 15996525
TI  - Adaptive functioning in children with seizures: impact of maternal anxiety about
      epilepsy.
AB  - This study evaluated the impact of maternal anxiety about a child's epilepsy on
      parental overprotection and the child's adaptive functioning. Specific maternal
      and family characteristics that contribute to elevated maternal anxiety about
      epilepsy were also studied over a year's time in a group of 56 mothers with
      children recently diagnosed with epilepsy. Overall, the primary predictor of
      maternal anxiety about epilepsy was the mother's level of coping resources,
      although family stress aggravated anxiety at the initial time point. Maternal
      anxiety about epilepsy was associated with overprotective and overly directive
      parenting styles, but it was the anxiety level itself that was most strongly
      related to the child's adaptive functioning. Maternal anxiety about epilepsy
      decreased over time, as did the relationship of maternal anxiety to the child's
      adaptive functioning. Nonetheless, after a year had elapsed, maternal anxiety was
      still associated with poorer adaptive skills.

PMID- 15996526
TI  - Suicide in the epilepsies: a meta-analytic investigation of 29 cohorts.
AB  - OBJECTIVES: Suicide in epilepsy is a major cause of death and is very often
      underestimated. We conducted a meta-analysis to compare data reported in
      representative studies of suicide in epilepsy with data for the general
      population. METHODS: We searched the Index Medicus until 2005 through MedLine. We
      also searched the World Health Statistics Annual to ascertain the suicide rates
      in the age groups indicated in the studies on epileptic patients for specific
      years and country. RESULTS: We selected 29 studies comprising 50,814 patients,
      187 of whom committed suicide. Results obtained for each study were processed
      together to calculate the mean number of suicides per 100,000 individuals
      suffering from epilepsy for each year. CONCLUSIONS: Our meta-analysis shows that
      suicide in patients with epilepsy is more frequent than in the general
      population. Nevertheless, a number of cohorts of epileptic patients had a suicide
      rate lower than that of the general population. Possible explanations for this
      heterogeneous trend and risk factors are discussed.

PMID- 15996527
TI  - What are the concerns of older adults living with epilepsy?
AB  - PURPOSE: The goal of this work was to examine the concerns of living with
      recurrent seizures as expressed by older adults with epilepsy (OAE). METHODS:
      Thirty-three community-dwelling adults over the age of 60 (mean age=65, range 60
      80) were surveyed as to their concerns living with epilepsy. All patients were
      being treated for intractable partial epilepsy (mean age at seizure onset=37,
      range 1-77) and all were receiving antiepileptic drugs (AEDs). Patients were
      given a blank sheet of paper and asked to list any concerns they had about living
      with epilepsy. Each patient listed his or her concerns in order of importance.
      RESULTS: Twenty-eight different areas of concern were listed by the OAE (range 1
      6 per patient). Concerns about driving/transportation (64%) and medication side
      effects (64%) were the most frequently listed concerns. Other concerns listed by
      >20% of patients included personal safety (39%), AED costs (29%), employment
      (26%), social embarrassment (21%), and memory loss (21%). Driving/transportation
      and AED side effects were the two most important concerns. CONCLUSIONS: Quality
      of-life issues in OAE appear similar in content to those of younger epilepsy
      groups. Driving/transportation, role restriction (i.e., grandparenting role),
      employment, social embarrassment, and safety are major concerns expressed by
      older adults. However, medication side effects appear more concerning to older
      adults as compared with earlier studies with younger patients. This study
      highlights the substantial burden of living with epilepsy in older adults and
      points to the challenges clinicians have when addressing them.

PMID- 15996528
TI  - Neurocutaneous syndromes: behavioral features.
AB  - Neurocutaneous syndromes are disorders characterized by a neurological
      abnormality and cutaneous manifestations. Three of the more common neurocutaneous
      syndromes are Sturge-Weber syndrome, tuberous sclerosis, and neurofibromatosis.
      This review focuses on the cognitive and behavioral features of these syndromes.

PMID- 15996529
TI  - Motor performance and behavior of immature rats are not compromised by a high
      dose of topiramate.
AB  - The first step in a study of possible cognitive side effects of topiramate in
      immature rats is to determine if and how topiramate (TPM) influences motor
      ability and spontaneous behavior. We therefore studied the effects of TPM on
      motor performance of 12- and 25-day-old rats using age-appropriate tests.
      Spontaneous behavior in the open field was studied in 25-day-old animals only.
      TPM was administered intraperitoneally at 80 and/or 160 mg/kg; control rats were
      injected with solvent (dimethylsulfoxide). A battery of motor tests was conducted
      before and 1, 3, and 24 hours after administration; behavior in the open field
      was recorded 2 and 24 hours after TPM administration. The effects of TPM on motor
      performance were similar to those of solvent. A few differences were found only
      at the 3-hour interval in 12-day-old rats. Behavior in the open field was not
      impaired by TPM; on the contrary, an apparent anxiolytic effect was observed.
      Habituation (a decrease in locomotor activity during the 5-minute observation
      period), a form of simple nonassociative learning, was also not compromised by
      TPM. A single high dose of TPM resulted only in transient changes in motor
      performance. A possible anxiolytic effect observed in 25-day-old rats should be
      studied.

PMID- 15996530
TI  - Periventricular heterotopia.
AB  - Periventricular heterotopia (PH) is clinically diagnosed on the basis of the
      radiographic characteristics of heterotopic nodules composed of disorganized
      neurons along the lateral ventricles of the brain. Epilepsy is the main
      presenting symptom of patients with PH. Behaviorally, patients generally are of
      normal intelligence, although there have been associated findings of learning
      disabilities, namely, dyslexia. Two genes responsible for PH have been
      identified: FilaminA, which encodes for the protein filamin A, and ARFGEF2, which
      encodes for the vesical transport-regulating protein ARFGEF2. The much more
      common X-linked dominant form of this disorder is due to filamin A, affects
      females, and is typically lethal in males. A much rarer autosomal recessive form
      due to ARFGEF2 mutations leads to microcephaly and developmental delay in
      addition to PH. Cell motility, adhesion defects, and weakening along the
      neuroepithelial lining may result from defects in these genes during cortical
      development and contribute to PH, but the mechanisms are not clear yet. Treatment
      of PH is largely symptomatic, following basic principles for epilepsy management
      and genetic counseling.

PMID- 15996531
TI  - Effects of voltage-gated Na+ channel toxins from Tityus serrulatus venom on rat
      arterial blood pressure and plasma catecholamines.
AB  - Scorpion toxins interact with ionic channels of excitable cells, leading to a
      massive release of neurotransmitters. Voltage-gated Na+ channel toxins are mainly
      responsible for the toxic effects of scorpion envenoming and can be classified
      into two classes: alpha- and beta-neurotoxins. TsTX-V and TsTX-I from Tityus
      serrulatus venom (TsV) are, respectively, examples of these toxins. In this work,
      we compared the effects of these toxins on mean arterial pressure (MAP) and
      catecholamines release in rats. Toxins were isolated by ion exchange
      chromatography (TsTX-I) followed by RP-HPLC (TsTX-V). All experiments were
      performed on conscious unrestrained rats previously catheterised. The toxins (15
      and 30 microg/kg) and TsV (50 and 100 microg/kg) were injected intravenously. MAP
      was continuously monitored through femoral catheter. Epinephrine (E) and
      norepinephrine (NE) levels were determined by RP-HPLC with electrochemical
      detection, at 10 min before and 2.5, 30 and 90 min after treatments. Maximal
      pressor effects were observed at 2.5-3.5 min. TsV induced intense long lasting
      increase in MAP, as did TsTX-I. TsTX-V showed the lowest pressor effects. TsV
      showed the highest effects on catecholamines release, followed by TsTX-I and TsTX
      V with maximal effect at 2.5 min, followed by a gradual reduction, however
      remaining higher than controls. Although both toxins act on Na+ channels, TsTX-I
      displayed significant and more intense effects on catecholamines release and
      blood pressure than TsTX-V. It seems that the toxicity of TsTX-V is not related
      only with its ability to release catecholamines, indicating that other
      neurotransmitters, may be involved in its toxicity.

PMID- 15996532
TI  - New probabilistic graphical models for genetic regulatory networks studies.
AB  - This paper introduces two new probabilistic graphical models for reconstruction
      of genetic regulatory networks using DNA microarray data. One is an independence
      graph (IG) model with either a forward or a backward search algorithm and the
      other one is a Gaussian network (GN) model with a novel greedy search method. The
      performances of both models were evaluated on four MAPK pathways in yeast and
      three simulated data sets. Generally, an IG model provides a sparse graph but a
      GN model produces a dense graph where more information about gene-gene
      interactions may be preserved. The results of our proposed models were compared
      with several other commonly used models, and our models have shown to give
      superior performance. Additionally, we found the same common limitations in the
      prediction of genetic regulatory networks when using only DNA microarray data.

PMID- 15996533
TI  - The stress system in the human brain in depression and neurodegeneration.
AB  - Corticotropin-releasing hormone (CRH) plays a central role in the regulation of
      the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in
      the stress response. The action of CRH on ACTH release is strongly potentiated by
      vasopressin, that is co-produced in increasing amounts when the hypothalamic
      paraventricular neurons are chronically activated. Whereas vasopressin stimulates
      ACTH release in humans, oxytocin inhibits it. ACTH release results in the release
      of corticosteroids from the adrenal that, subsequently, through mineralocorticoid
      and glucocorticoid receptors, exert negative feedback on, among other things, the
      hippocampus, the pituitary and the hypothalamus. The most important
      glucocorticoid in humans is cortisol, present in higher levels in women than in
      men. During aging, the activation of the CRH neurons is modest compared to the
      extra activation observed in Alzheimer's disease (AD) and the even stronger
      increase in major depression. The HPA-axis is hyperactive in depression, due to
      genetic factors or due to aversive stimuli that may occur during early
      development or adult life. At least five interacting hypothalamic peptidergic
      systems are involved in the symptoms of major depression. Increased production of
      vasopressin in depression does not only occur in neurons that colocalize CRH, but
      also in neurons of the supraoptic nucleus (SON), which may lead to increased
      plasma levels of vasopressin, that have been related to an enhanced suicide risk.
      The increased activity of oxytocin neurons in the paraventricular nucleus (PVN)
      may be related to the eating disorders in depression. The suprachiasmatic nucleus
      (SCN), i.e., the biological clock of the brain, shows lower vasopressin
      production and a smaller circadian amplitude in depression, which may explain the
      sleeping problems in this disorder and may contribute to the strong CRH
      activation. The hypothalamo-pituitary thyroid (HPT)-axis is inhibited in
      depression. These hypothalamic peptidergic systems, i.e., the HPA-axis, the SCN,
      the SON and the HPT-axis, have many interactions with aminergic systems that are
      also implicated in depression. CRH neurons are strongly activated in depressed
      patients, and so is their HPA-axis, at all levels, but the individual variability
      is large. It is hypothesized that particularly a subgroup of CRH neurons that
      projects into the brain is activated in depression and induces the symptoms of
      this disorder. On the other hand, there is also a lot of evidence for a direct
      involvement of glucocorticoids in the etiology and symptoms of depression.
      Although there is a close association between cerebrospinal fluid (CSF) levels of
      CRH and alterations in the HPA-axis in depression, much of the CRH in CSF is
      likely to be derived from sources other than the PVN. Furthermore, a close
      interaction between the HPA-axis and the hypothalamic-pituitary-gonadal (HPG)
      axis exists. Organizing effects during fetal life as well as activating effects
      of sex hormones on the HPA-axis have been reported. Such mechanisms may be a
      basis for the higher prevalence of mood disorders in women as compared to men. In
      addition, the stress system is affected by changing levels of sex hormones, as
      found, e.g., in the premenstrual period, ante- and postpartum, during the
      transition phase to the menopause and during the use of oral contraceptives. In
      depressed women, plasma levels of estrogen are usually lower and plasma levels of
      androgens are increased, while testosterone levels are decreased in depressed
      men. This is explained by the fact that both in depressed males and females the
      HPA-axis is increased in activity, parallel to a diminished HPG-axis, while the
      major source of androgens in women is the adrenal, whereas in men it is the
      testes. It is speculated, however, that in the etiology of depression the
      relative levels of sex hormones play a more important role than their absolute
      levels. Sex hormone replacement therapy indeed seems to improve mood in elderly
      people and AD patients. Studies of rats have shown that high levels of cumulative
      corticosteroid exposure and rather extreme chronic stress induce neuronal damage
      that selectively affects hippocampal structure. Studies performed under less
      extreme circumstances have so far provided conflicting data. The corticosteroid
      neurotoxicity hypothesis that evolved as a result of these initial observations
      is, however, not supported by clinical and experimental observations. In a few
      recent postmortem studies in patients treated with corticosteroids and patients
      who had been seriously and chronically depressed no indications for AD
      neuropathology, massive cell loss, or loss of plasticity could be found, while
      the incidence of apoptosis was extremely rare and only seen outside regions
      expected to be at risk for steroid overexposure. In addition, various recent
      experimental studies using good stereological methods failed to find massive cell
      loss in the hippocampus following exposure to stress or steroids, but rather
      showed adaptive and reversible changes in structural parameters after stress.
      Thus, the HPA-axis in AD is only moderately activated, possibly due to the
      initial (primary) hippocampal degeneration in this condition. There are no
      convincing arguments to presume a causal, primary role for cortisol in the
      pathogenesis of AD. Although cortisol and CRH may well be causally involved in
      the signs and symptoms of depression, there is so far no evidence for any major
      irreversible damage in the human hippocampus in this disorder.

PMID- 15996534
TI  - Binding of MutS mismatch repair protein to DNA containing UV photoproducts,
      "mismatched" opposite Watson--Crick and novel nucleotides, in different DNA
      sequence contexts.
AB  - Mismatch-repair (MMR) systems suppress mutation via correction of DNA replication
      errors (base-mispairs) and responses to mutagenic DNA lesions. Selective binding
      of mismatched or damaged DNA by MutS-homolog proteins-bacterial MutS, eukaryotic
      MSH2.MSH6 (MutSalpha) and MSH2.MSH3-initiates mismatch-correction pathways and
      responses to lesions, and may cumulatively increase discrimination at downstream
      steps. MutS-homolog binding selectivity and the well-known but poorly understood
      effects of DNA-sequence contexts on recognition may thus be primary determinants
      of MMR specificity and efficiency. MMR processes that modulate UV mutagenesis
      might begin with selective binding by MutS homologs of "mismatched" T[CPD]T/AG
      and T[6--4]T/AG photoproducts, reported previously for hMutSalpha and described
      here for E. coli MutS protein. If MMR suppresses UV mutagenesis by acting
      directly on pre-mutagenic products of replicative bypass, mismatched
      photoproducts should be recognized in most DNA-sequence contexts. In three of
      four contexts tested here (three substantially different), T[CPD]T/AG was bound
      only slightly better by MutS than was T[CPD]T/AA or homoduplex DNA; only one of
      two contexts tested promoted selective binding of T[6--4]T/AG. Although the T:G
      pairs in T[CPD]T/AG and T/G both adopt wobble conformations, MutS bound T/G well
      in all contexts (K(1/2) 2.1--2.9 nM). Thus, MutS appears to select the two
      mismatches by different mechanisms. NMR analyses elsewhere suggest that in the
      (highly distorted) T[6--4]T/AG a forked H-bond between O2 of the 3' thymine and
      the ring 1-imino and exocyclic 2-amino guanine protons stabilizes a novel planar
      structure not possible in T[6--4]T/AA. Replacement of G by purines lacking one
      (inosine, 2-aminopurine) or both (nebularine) protons markedly reduced or
      eliminated selective MutS binding, as predicted. Previous studies and the work
      here, taken together, suggest that in only about half of DNA sequence contexts
      could MutS (and presumably MutSalpha) selectively bind mismatched UV
      photoproducts and directly suppress UV mutagenesis.

PMID- 15996535
TI  - Determination of tadalafil in small volumes of plasma by high-performance liquid
      chromatography with UV detection.
AB  - Tadalafil is a potent reversible phosphodiesterase-5 inhibitor used for the
      treatment of erectile dysfunction. This study describes a simple and sensitive
      high-performance liquid chromatographic (HPLC) method for the determination of
      tadalafil in 50 microl of rat plasma. Tadalafil and the internal standard
      lamotrigine were extracted with 0.5 ml of tert-butyl methyl ether, after the
      samples alkalinized with 20 microl of sodium hydroxide solution (1N).
      Chromatographic separation was achieved on a C18 column with the mobile phase of
      acetonitrile-water containing 20 mM phosphate buffer (pH 7) (35/65, v/v), at a
      flow rate of 1 ml/min. The eluant was detected at 290 nm. The retention time was
      about 4.5 min for lamotrigine and 15 min for tadalafil. No endogenous substances
      were found to interfere. Calibration curves were linear from 10 to 2000 ng/ml.
      The recovery of tadalafil from plasma was greater than 77%. The limit of
      quantitation was 10 ng/ml. The intra- and inter-day imprecision (expressed as
      coefficient of variation, C.V.) did not exceed 10.7%, and the accuracy was within
      5.9% deviation of the nominal concentration. The method is suitable in
      pharmacokinetic investigation and monitoring tadalafil concentration.

PMID- 15996536
TI  - Gas chromatograph-mass spectrometric method for the determination of carvedilol
      and its metabolites in human urine.
AB  - A sensitive and efficient method was developed for the determination of
      carvedilol and its metabolites in human urine by gas chromatography-mass
      spectrometry (GC-MS). Urine samples were hydrolyzed with beta
      glucuronidase/arylsulfatase (from Helix pomatia) and the target compounds were
      extracted with liquid-liquid extraction. The extracts were completely derivatized
      with MSTFA and MBTFA and analyzed by GC-MS using an Ultra-2 column. The linearity
      of the assay ranges were 0.75-75 ngmL(-1) for carvedilol and o-desmethyl
      carvedilol (o-DMC), and 3.0-75 ngmL(-1) for 4-hydroxyphenyl carvedilol (4-HPC)
      and 5-hydroxyphenyl carvedilol (5-HPC). The absolute recovery of carvedilol and
      its metabolites added to a blank urine sample was 80.1-97.8%. The limits of
      detection (LOD) and quantitation (LOQ) of carvedilol and o-DMC were 0.30 and 0.75
      ngmL(-1), and its of 4-HPC and 5-HPC were 0.75 and 3.0 ngmL(-1), respectively.
      The reproducibilities were 1.86-11.5% for the intra-day assay, and 0.70-1.71% for
      the inter-day assay precision and the degree of inaccuracy was -3.0 to 3.9% at
      the concentration of 75 ngmL(-1). The proposed GC-MS method was effective for the
      determination of carvedilol and its three metabolites in human urine.

PMID- 15996537
TI  - A validated method for the quantification of enterodiol and enterolactone in
      plasma using isotope dilution liquid chromatography with tandem mass
      spectrometry.
AB  - Enterolactone and enterodiol are phytoestrogens with structural similarity to
      endogenous estrogens. Because of their biological activities, they may affect the
      development of several diseases. To quantify enterodiol and enterolactone in
      plasma, we developed and validated a liquid chromatography-tandem mass
      spectrometry method with electrospray ionization using 13C3 labeled isotopes. The
      method consists of a simple enzymatic hydrolysis and ether extraction followed by
      a rapid LC separation (run-time of 11 min). Detection limits as low as 0.15 nM
      for enterodiol and 0.55 nM for enterolactone were achieved. The within-run R.S.D.
      ranges from 3 to 6% and the between-run R.S.D. ranges from 10 to 14% for both
      enterolignans. This method allows simple, rapid, and sensitive quantification,
      and is suitable for measuring large numbers of samples.

PMID- 15996538
TI  - High performance liquid chromatographic determination of topiramate in human
      serum using UV detection.
AB  - Topiramate has no ultraviolet, visible or fluorescence absorption. Analysis of
      the drug in human serum has been reported by high performance liquid
      chromatography (HPLC) with either mass detector or fluorescence detection after
      precolumn derivatization using 9-fluorenylmethyl chloroformate as fluorescent
      labeling agent. This study was aimed to validate derivatization and analysis of
      topiramate in human serum with HPLC using UV detection. The drug was extracted
      from human serum by liquid-liquid extraction and subjected to derivatization with
      9-fluorenylmethyl chloroformate. Analysis was performed on a phenyl column using
      of spectrophotometer detection operated at wavelength of 264 nm. A mixture of
      phosphate buffer (0.05M) containing triethylamine (1 ml/l, v/v; pH 2.3) and
      methanol (28:72, v/v) at a flow rate of 2.5 ml/min was used as mobile phase. No
      interference was found with endogenous substances. Validity of the method was
      studied and the method was precise and accurate with a linearity range from 40
      ng/ml to 40 microg/ml. The limit of quantification was 40 ng/ml of serum. The
      correlation coefficient between HPLC methods using fluorescence and UV detections
      was studied and found to be 0.992.

PMID- 15996539
TI  - Preliminary investigation of using volatile organic compounds from human expired
      air, blood and urine for locating entrapped people in earthquakes.
AB  - A preliminary investigation on the possibility of using volatile organic
      compounds (VOCs) determination of expired air, blood and urine, for the early
      location of entrapped people in earthquakes, has been carried out. A group of 15
      healthy subjects has been sampled. The identification of a common "core" of
      substances might provide indications of human presence that can be used for the
      development of a real time field analytical method for the on site detection of
      entrapped people. Expired air samples have been analyzed by thermal desorption
      GC/MS and VOCs from blood and urine by headspace SPME-GC/MS. Acetone was the only
      compound found common in all three matrices. Isoprene was found in both expired
      air and blood samples. Acetone and isoprene along with a number of saturated
      hydrocarbons were among the major constituents identified in expired air
      analysis. Various ketones (2-pentanone, 4-heptanone, 2-butanone) were also
      determined over urine specimens. Using the techniques and methods of field
      analytical chemistry and technology appears to be the proper approach for
      applying the results of the present study in real situations.

PMID- 15996540
TI  - Recent advances in imaging the fetus and newborn.

PMID- 15996541
TI  - The power of the dark side: Huntington's disease protein and p53 form a deadly
      alliance.
AB  - A role for apoptotic mediators in neurodegenerative disease has long been
      considered, but the identity of the putative effectors and the basis of their
      actions in neurodegeneration remain ill-defined. Huntington's disease (HD) is a
      polyglutamine disorder whose pathogenesis likely involves mitochondrial
      dysfunction. In this issue of Neuron, Bae et al. present data implicating p53 in
      HD pathogenesis. This intriguing study may thus provide a link between nuclear
      transcription dysregulation and mitochondrial abnormalities in HD.

PMID- 15996542
TI  - Sniffing Out NMDA Receptors in the Olfactory Cortex.
AB  - Selective olfactory learning is essential for survival in most newborn mammals.
      Findings by Franks and Isaacson in this issue of Neuron suggest that early
      olfactory learning might be selective, in part because olfactory experience
      downregulates NMDA receptors at primary inputs to the olfactory cortex.

PMID- 15996543
TI  - Resolving border disputes in midlevel vision.
AB  - Two papers in this issue of Neuron specify the coding of border ownership, the
      basis of figure-ground segmentation, in early extrastriate visual cortex (area
      V2). Recording from a population of neurons, Qiu and von der Heydt show that
      border ownership assignments based on 2D images show the same bias when tested
      with stereopsis. Zhaoping shows that a neural model of V2 can make appropriate
      border assignments based on 2D images.

PMID- 15996544
TI  - Mental concerts: musical imagery and auditory cortex.
AB  - Most people intuitively understand what it means to "hear a tune in your head."
      Converging evidence now indicates that auditory cortical areas can be recruited
      even in the absence of sound and that this corresponds to the phenomenological
      experience of imagining music. We discuss these findings as well as some
      methodological challenges. We also consider the role of core versus belt areas in
      musical imagery, the relation between auditory and motor systems during imagery
      of music performance, and practical implications of this research.

PMID- 15996545
TI  - The Mauthner cell half a century later: a neurobiological model for decision
      making?
AB  - The Mauthner (M) cell is a critical element in a vital escape "reflex" triggered
      by abrupt or threatening events. Its properties at the molecular and synaptic
      levels, their various forms of plasticity, and the design of its networks, are
      all well adapted for this survival function. They guarantee that this behavior is
      appropriately unilateral, variable, and unpredictable. The M cell sets the
      behavioral threshold, and, acting in concert with other elements of the brainstem
      escape network, determines when, where, and how the escape is executed.

PMID- 15996546
TI  - p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's
      disease.
AB  - We present evidence for a specific role of p53 in the mitochondria-associated
      cellular dysfunction and behavioral abnormalities of Huntington's disease (HD).
      Mutant huntingtin (mHtt) with expanded polyglutamine (polyQ) binds to p53 and
      upregulates levels of nuclear p53 as well as p53 transcriptional activity in
      neuronal cultures. The augmentation is specific, as it occurs with mHtt but not
      mutant ataxin-1 with expanded polyQ. p53 levels are also increased in the brains
      of mHtt transgenic (mHtt-Tg) mice and HD patients. Perturbation of p53 by
      pifithrin-alpha, RNA interference, or genetic deletion prevents mitochondrial
      membrane depolarization and cytotoxicity in HD cells, as well as the decreased
      respiratory complex IV activity of mHtt-Tg mice. Genetic deletion of p53
      suppresses neurodegeneration in mHtt-Tg flies and neurobehavioral abnormalities
      of mHtt-Tg mice. Our findings suggest that p53 links nuclear and mitochondrial
      pathologies characteristic of HD.

PMID- 15996547
TI  - Early stages of zebrafish eye formation require the coordinated activity of
      Wnt11, Fz5, and the Wnt/beta-catenin pathway.
AB  - During regional patterning of the anterior neural plate, a medially positioned
      domain of cells is specified to adopt retinal identity. These eye field cells
      remain coherent as they undergo morphogenetic events distinct from other
      prospective forebrain domains. We show that two branches of the Wnt signaling
      pathway coordinate cell fate determination with cell behavior during eye field
      formation. Wnt/beta-catenin signaling antagonizes eye specification through the
      activity of Wnt8b and Fz8a. In contrast, Wnt11 and Fz5 promote eye field
      development, at least in part, through local antagonism of Wnt/beta-catenin
      signaling. Additionally, Wnt11 regulates the behavior of eye field cells,
      promoting their cohesion. Together, these results allow us to postulate a model
      in which Wnt11 and Fz5 signaling promotes early eye development through the
      coordinated antagonism of signals that suppress retinal identity and promotion of
      coherence of eye field cells.

PMID- 15996548
TI  - Opposing gradients of ephrin-As and EphA7 in the superior colliculus are
      essential for topographic mapping in the mammalian visual system.
AB  - During development of the retinocollicular projection in mouse, retinal axons
      initially overshoot their future termination zones (TZs) in the superior
      colliculus (SC). The formation of TZs is initiated by interstitial branching at
      topographically appropriate positions. Ephrin-As are expressed in a decreasing
      posterior-to-anterior gradient in the SC, and they suppress branching posterior
      to future TZs. Here we investigate the role of an EphA7 gradient in the SC, which
      has the reverse orientation to the ephrin-A gradient. We find that in EphA7
      mutant mice the retinocollicular map is disrupted, with nasal and temporal axons
      forming additional or extended TZs, respectively. In vitro, retinal axons are
      repelled from growing on EphA7-containing stripes. Our data support the idea that
      EphA7 is involved in suppressing branching anterior to future TZs. These findings
      suggest that opposing ephrin-A and EphA gradients are required for the proper
      development of the retinocollicular projection.

PMID- 15996549
TI  - Mechanism of partial agonist action at the NR1 subunit of NMDA receptors.
AB  - Partial agonists produce submaximal activation of ligand-gated ion channels. To
      address the question of partial agonist action at the NR1 subunit of the NMDA
      receptor, we performed crystallographic and electrophysiological studies with 1
      aminocyclopropane-1-carboxylic acid (ACPC), 1-aminocyclobutane-1-carboxylic acid
      (ACBC), and 1-aminocyclopentane-1-carboxylic acid (cycloleucine), three compounds
      with incrementally larger carbocyclic rings. Whereas ACPC and ACBC partially
      activate the NMDA receptor by 80% and 42%, respectively, their cocrystal
      structures of the NR1 ligand binding core show the same degree of domain closure
      as found in the complex with glycine, a full agonist, illustrating that the NR1
      subunit provides a new paradigm for partial agonist action that is distinct from
      that of the evolutionarily related GluR2, AMPA-sensitive receptor. Cycloleucine
      behaves as an antagonist and stabilizes an open-cleft conformation. The NR1
      cycloleucine complex forms a dimer that is similar to the GluR2 dimer, thereby
      suggesting a conserved mode of subunit-subunit interaction in AMPA and NMDA
      receptors.

PMID- 15996550
TI  - The Rho-specific GEF Lfc interacts with neurabin and spinophilin to regulate
      dendritic spine morphology.
AB  - Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding
      proteins that regulate dendritic spine function. A yeast two-hybrid analysis
      using the coiled-coil domain of neurabin revealed an interaction with Lfc, a Rho
      GEF. Lfc was highly expressed in brain, where it interacted with either neurabin
      or spinophilin. In neurons, Lfc was largely found in the shaft of dendrites in
      association with microtubules but translocated to spines upon neuronal
      stimulation. Moreover, expression of Lfc resulted in reduction in spine length
      and size. Both the translocation and the effect on spine morphology depended on
      the coiled-coil domain of Lfc. Coexpression of neurabin or spinophilin with Lfc
      resulted in their clustering together with F-actin, a process that depended on
      Rho activity. Thus, interaction between Lfc and neurabin/spinophilin selectively
      regulates Rho-dependent organization of F-actin in spines and is a link between
      the microtubule and F-actin cytoskeletons in dendrites.

PMID- 15996551
TI  - Synapse-specific downregulation of NMDA receptors by early experience: a critical
      period for plasticity of sensory input to olfactory cortex.
AB  - Olfaction is required at birth for survival; however, little is known about the
      maturation of olfactory cortical circuits. Here we show that in vivo sensory
      experience mediates the development of excitatory transmission in pyramidal
      neurons of rat olfactory cortex. We find a postnatal critical period during which
      there is an experience-dependent increase in the contribution of AMPARs versus
      NMDARs to transmission at primary sensory synapses but not associational inputs.
      The shift in receptors underlying transmission is mediated by a strong activity
      dependent downregulation of NMDARs and modest increase in AMPARs. Sensory
      activity leads to a loss of "silent" NMDAR-only synapses and an increase in
      threshold for inducing long-term plasticity. These results indicate the
      importance of early olfactory experience in the establishment of cortical
      circuits and could reflect mechanisms governing early olfactory "imprinting."

PMID- 15996552
TI  - Serotonin modulates circadian entrainment in Drosophila.
AB  - Entrainment of the Drosophila circadian clock to light involves the light-induced
      degradation of the clock protein timeless (TIM). We show here that this
      entrainment mechanism is inhibited by serotonin, acting through the Drosophila
      serotonin receptor 1B (d5-HT1B). d5-HT1B is expressed in clock neurons, and
      alterations of its levels affect molecular and behavioral responses of the clock
      to light. Effects of d5-HT1B are synergistic with a mutation in the circadian
      photoreceptor cryptochrome (CRY) and are mediated by SHAGGY (SGG), Drosophila
      glycogen synthase kinase 3beta (GSK3beta), which phosphorylates TIM. Levels of
      serotonin are decreased in flies maintained in extended constant darkness,
      suggesting that modulation of the clock by serotonin may vary under different
      environmental conditions. These data identify a molecular connection between
      serotonin signaling and the central clock component TIM and suggest a homeostatic
      mechanism for the regulation of circadian photosensitivity in Drosophila.

PMID- 15996553
TI  - Midbrain dopamine neurons encode a quantitative reward prediction error signal.
AB  - The midbrain dopamine neurons are hypothesized to provide a physiological
      correlate of the reward prediction error signal required by current models of
      reinforcement learning. We examined the activity of single dopamine neurons
      during a task in which subjects learned by trial and error when to make an eye
      movement for a juice reward. We found that these neurons encoded the difference
      between the current reward and a weighted average of previous rewards, a reward
      prediction error, but only for outcomes that were better than expected. Thus, the
      firing rate of midbrain dopamine neurons is quantitatively predicted by
      theoretical descriptions of the reward prediction error signal used in
      reinforcement learning models for circumstances in which this signal has a
      positive value. We also found that the dopamine system continued to compute the
      reward prediction error even when the behavioral policy of the animal was only
      weakly influenced by this computation.

PMID- 15996554
TI  - Border ownership from intracortical interactions in visual area v2.
AB  - A border between two image regions normally belongs to only one of the regions;
      determining which one it belongs to is essential for surface perception and
      figure-ground segmentation. Border ownership is signaled by a class of V2
      neurons, even though its value depends on information coming from well outside
      their classical receptive fields. I use a model of V2 to show that this visual
      area is able to generate the ownership signal by itself, without requiring any
      top-down mechanism or external explicit labels for figures, T junctions, or
      corners. In the model, neurons have spatially local classical receptive fields,
      are tuned to orientation, and receive information (from V1) about the location
      and orientation of borders. Border ownership signals that model physiological
      observations arise through finite range, intraareal interactions. Additional
      effects from surface features and attention are discussed. The model licenses
      testable predictions.

PMID- 15996555
TI  - Figure and ground in the visual cortex: v2 combines stereoscopic cues with
      gestalt rules.
AB  - Figure-ground organization is a process by which the visual system identifies
      some image regions as foreground and others as background, inferring 3D layout
      from 2D displays. A recent study reported that edge responses of neurons in area
      V2 are selective for side-of-figure, suggesting that figure-ground organization
      is encoded in the contour signals (border ownership coding). Here, we show that
      area V2 combines two strategies of computation, one that exploits binocular
      stereoscopic information for the definition of local depth order, and another
      that exploits the global configuration of contours (Gestalt factors). These are
      combined in single neurons so that the "near" side of the preferred 3D edge
      generally coincides with the preferred side-of-figure in 2D displays. Thus, area
      V2 represents the borders of 2D figures as edges of surfaces, as if the figures
      were objects in 3D space. Even in 3D displays, Gestalt factors influence the
      responses and can enhance or null the stereoscopic depth information.

PMID- 15996556
TI  - Gesture is at the cutting edge of early language development.
AB  - Children who produce one word at a time often use gesture to supplement their
      speech, turning a single word into an utterance that conveys a sentence-like
      meaning ('eat'+point at cookie). Interestingly, the age at which children first
      produce supplementary gesture-speech combinations of this sort reliably predicts
      the age at which they first produce two-word utterances. Gesture thus serves as a
      signal that a child will soon be ready to begin producing multi-word sentences.
      The question is what happens next. Gesture could continue to expand a child's
      communicative repertoire over development, combining with words to convey
      increasingly complex ideas. Alternatively, after serving as an opening wedge into
      language, gesture could cease its role as a forerunner of linguistic change. We
      addressed this question in a sample of 40 typically developing children, each
      observed at 14, 18, and 22 months. The number of supplementary gesture-speech
      combinations the children produced increased significantly from 14 to 22 months.
      More importantly, the types of supplementary combinations the children produced
      changed over time and presaged changes in their speech. Children produced three
      distinct constructions across the two modalities several months before these same
      constructions appeared entirely within speech. Gesture thus continues to be at
      the cutting edge of early language development, providing stepping-stones to
      increasingly complex linguistic constructions.

PMID- 15996557
TI  - The capacity of visual short-term memory within and between hemifields.
AB  - Visual short-term memory (VSTM) and attention are both thought to have a capacity
      limit of four items [e.g. Luck, S. J., & Vogel, E. K. (1997). The capacity of
      visual working memory for features and conjunctions. Nature, 309, 279-281;
      Pylyshyn, Z. W., & Storm, R. W. (1988). Tracking multiple independent targets:
      evidence for a parallel tracking mechanism. Spatial Vision, 3, 179-197.]. Using
      the multiple object visual tracking paradigm (MOT), it has recently been shown
      that twice as many items can be simultaneously attended when they are separated
      between two visual fields compared to when they are all presented within the same
      hemifield [Alvarez, G. A., & Cavanagh, P. (2004). Independent attention resources
      for the left and right visual hemifields (Abstract). Journal of Vision, 4(8),
      29a.]. Does VSTM capacity also increase when the items to be remembered are
      distributed between the two visual fields? The current paper investigated this
      central issue in two different tasks, namely a color and spatial location change
      detection task, in which the items were displayed either in the two visual fields
      or in the same hemifield. The data revealed that only memory capacity for spatial
      locations and not colors increased when the items were separated between the two
      visual fields. These findings support the view of VSTM as a chain of capacity
      limited operations where the spatial selection of stimuli, which dominates in
      both spatial location VSTM and MOT, occupies the first place and shows
      independence between the two fields.

PMID- 15996558
TI  - Developing knowledge of objects' motion properties in infancy.
AB  - Three experiments with a novel variation of the inductive generalization
      procedure examined 18- and 22-month-olds' knowledge of objects' motion
      properties. Infants observed simple air and land movements modeled with an
      appropriate category member (e.g. dog) or an ambiguous block and were allowed to
      imitate with one or more of four exemplars. The experiments show that 18-month
      olds' knowledge of land motions is grounded in causally relevant object parts,
      whereas 22-month-olds relate such motions more broadly to appropriate category
      members. Infants' basis for generalizing air motions suggested that at 22 months
      they have little knowledge about objects from that domain. The results are
      discussed in relation to the early development of the animate-inanimate
      distinction and the nature of the inductive generalization task.

PMID- 15996559
TI  - A specific role for efferent information in self-recognition.
AB  - We investigated the specific contribution of efferent information in a self
      recognition task. Subjects experienced a passive extension of the right index
      finger, either as an effect of moving their left hand via a lever ('self
      generated action'), or imposed externally by the experimenter ('externally
      generated action'). The visual feedback was manipulated so that subjects saw
      either their own right hand ('view own hand' condition) or someone else's right
      hand ('view other's hand' condition) during the passive extension of the index
      finger. Both hands were covered with identical gloves, so that discrimination on
      the basis of morphological differences was not possible. Participants judged
      whether the right hand they saw was theirs or not. Self-recognition was
      significantly more accurate when subjects were themselves the authors of the
      action, even though visual and proprioceptive information always specified the
      same posture, and despite the fact that subjects judged the effect and not the
      action per se. When the passive displacement of the participants right index
      finger was externally generated, and only afferent information was available,
      self-recognition performance dropped to near-chance levels. Differences in
      performance across conditions reflect the distinctive contribution of efferent
      information to self-recognition, and argue against a dominant role of
      proprioception in self-recognition.

PMID- 15996560
TI  - Stress changes the representational landscape: evidence from word segmentation.
AB  - Over the past couple of decades, research has established that infants are
      sensitive to the predominant stress pattern of their native language. However,
      the degree to which the stress pattern shapes infants' language development has
      yet to be fully determined. Whether stress is merely a cue to help organize the
      patterns of speech or whether it is an important part of the representation of
      speech sound sequences has still to be explored. Building on research in the
      areas of infant speech perception and segmentation, we asked how several months
      of exposure to the target language shapes infants' speech processing biases with
      respect to lexical stress. We hypothesize that infants represent stressed and
      unstressed syllables differently, and employed analyses of child-directed speech
      to show how this change to the representational landscape results in better
      distribution-based word segmentation as well as an advantage for stress-initial
      syllable sequences. A series of experiments then tested 9- and 7-month-old
      infants on their ability to use lexical stress without any other cues present to
      parse sequences from an artificial language. We found that infants adopted a
      stress-initial syllable strategy and that they appear to encode stress
      information as part of their proto-lexical representations. Together, the results
      of these studies suggest that stress information in the ambient language not only
      shapes how statistics are calculated over the speech input, but that it is also
      encoded in the representations of parsed speech sequences.

PMID- 15996561
TI  - How do speakers avoid ambiguous linguistic expressions?
AB  - Three experiments assessed how speakers avoid linguistically and
      nonlinguistically ambiguous expressions. Speakers described target objects (a
      flying mammal, bat) in contexts including foil objects that caused linguistic (a
      baseball bat) and nonlinguistic (a larger flying mammal) ambiguity. Speakers
      sometimes avoided linguistic-ambiguity, and they did so equally regardless of
      whether they also were about to describe foils. This suggests that comprehension
      processes can sometimes detect linguistic-ambiguity before producing it. However,
      once produced, speakers consistently avoided using the same linguistically
      ambiguous expression again for a different meaning. This suggests that production
      processes can successfully detect linguistic-ambiguity after-the-fact. Speakers
      almost always avoided nonlinguistic-ambiguity. Thus, production processes are
      especially sensitive to nonlinguistic- but not linguistic-ambiguity, with the
      latter avoided consistently only once it is already articulated.

PMID- 15996562
TI  - Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A)
      receptor activation in attenuation of catalepsy induction in rats.
AB  - Compounds possessing 5-HT(1A) agonist properties attenuate catalepsy induced by
      D(2) receptor blockade. Here we examined the role of 5-HT(1A) receptor agonism in
      the reduced cataleptogenic potential of several novel antipsychotic agents in the
      crossed leg position (CLP) and the bar catalepsy tests in rats. When administered
      alone, ziprasidone produced marked catalepsy, whereas aripiprazole, bifeprunox,
      SLV313, SSR181507 and sarizotan did not. However, when 5-HT(1A) receptors were
      blocked with the selective antagonist, WAY100635 (0.63 mg/kg, SC), robust
      cataleptogenic properties of SLV313, bifeprunox and sarizotan were unmasked and
      the catalepsy induced by ziprasidone was accentuated. In contrast, only modest
      catalepsy was induced by aripiprazole and SSR181507, even following a higher dose
      of WAY100635 (2.5 mg/kg). This suggests that these compounds possess other anti
      cataleptic properties, such as partial agonism at dopamine D(2) receptors. The
      capacity to reverse neuroleptic-induced catalepsy was investigated in interaction
      studies with haloperidol (2.5 mg/kg, SC). Whereas ziprasidone and aripiprazole
      did not markedly reduce the effects of haloperidol, SLV313 and sarizotan
      attenuated CLP catalepsy. In contrast, SSR181507 and bifeprunox potently
      inhibited both CLP and bar catalepsy. Taken together, these data show that 5
      HT(1A) receptor activation reduces the cataleptogenic potential of novel
      antipsychotic agents but indicate marked diversity in the contribution of 5
      HT(1A) and/or other mechanisms to the profiles of the drugs.

PMID- 15996563
TI  - Design of antagonists for NMDA and AMPA receptors.
AB  - Determinants of antagonism of NMDA and calcium permeable AMPA receptor channels
      by organic cations were studied using several homologous series of mono- and
      dicationic derivatives of adamantane, phenylcyclohexyl, triphenylmethane,
      diphenylmethane. Antagonism by these drugs was studied on native receptors of
      isolated rat brain neurons and on recombinant GluR1 receptors expressed by
      Xenopus oocytes. The major action of these compounds was on the open channel,
      although minor competitive or closed channel antagonism cannot be ruled out.
      Analysis of structure-activity relationships suggests that all organic
      monocations are selective antagonists of NMDA receptors. Compounds exhibiting
      trapping block are more potent than those exhibiting weakly-trapping block. AMPA
      and NMDA receptor channels are blocked by dicationic organic compounds, the
      former requiring a certain distance between the hydrophobic moiety and the
      terminal charged group. Variations of their terminal ammonium group demonstrated
      that trimethylammonium derivatives are the most potent antagonists of AMPA
      receptors, whereas the terminal amino group is optimal for block of NMDA
      receptors. Based on the action of 38 compounds, topographical models of the
      binding sites of these compounds on NMDA and AMPA receptor channels are
      presented. These models will help to design channel-blocking drugs with defined
      potency and selectivity of action.

PMID- 15996564
TI  - Inhibitory effect of imipramine on the human corticotropin-releasing-hormone gene
      promoter activity operates through a PI3-K/AKT mediated pathway.
AB  - Antidepressant drugs inhibit the corticotropin-releasing-hormone (CRH) gene
      promoter activity in the differentiated Neuro-2A cells, but a molecular mechanism
      of their action has been poorly recognized. The aim of the present study was to
      elucidate the involvement of some intracellular signal transduction pathways in
      imipramine-induced inhibition of CRH gene activity in the differentiated Neuro-2A
      cells, stably transfected with a human CRH promoter fragment linked to the
      chloramphenicol acetyltransferase (CAT) reporter gene. It was found that
      wortmannin (0.1muM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K) and
      forskolin (10, 25muM), an activator of adenylate cyclase enhanced the basal
      activity of CRH gene promoter, whereas inhibitors of protein kinase A,
      calcium/calmodulin kinase (CaMK) and mitogen-activated protein kinase (MAPK) had
      opposite effects. Moreover, wortmannin at a low concentration (0.01muM)
      significantly reversed the inhibitory effect of imipramine on CRH-CAT activity,
      whereas other protein kinase inhibitors were inactive or even enhanced the
      imipramine effects. The involvement of PI3-K/Akt pathway in the imipramine action
      was confirmed by Western blot study, which showed that this drug increased
      phospho-Ser-473 Akt level, but had no effect on total Akt and glycogen synthase
      kinase (GSK-3beta) levels. These results indicate that the inhibitory effect of
      imipramine on the CRH gene promoter activity in Neuro-2A cells is mainly
      connected with enhancement of PI-3K/Akt pathway.

PMID- 15996565
TI  - Naltrexone in the short-term decreases antiparkinsonian response to l-Dopa and in
      the long-term increases dyskinesias in drug-naive parkinsonian monkeys.
AB  - Nigrostriatal dopaminergic denervation and levodopa therapy in animal models and
      in parkinsonian patients are associated with an enhanced opioid transmission in
      the striatum. The functional role of this increase has always been a subject of
      debate. In this study two groups of drug-naive macaque monkeys with MPTP-induced
      parkinsonism were treated daily, during four weeks, with l-Dopa alone or l-Dopa
      plus naltrexone, a non-selective opioid receptor antagonist. The improvement of
      parkinsonism in all animals treated with l-Dopa alone was clearly displayed from
      the first day of treatment. By contrast, naltrexone co-treatment blocked the
      antiparkinsonian action of l-Dopa for 7-14 days. As soon as the therapeutical
      action of l-Dopa appeared in naltrexone-treated monkeys, the magnitude and
      duration of the antiparkinsonian response were similar in both groups.
      Furthermore, in animals treated with l-Dopa plus naltrexone the beginning of the
      therapeutical effect of l-Dopa was accompanied by the appearance of dyskinesias.
      In this group, the severity of dyskinesias during the third and fourth weeks of
      treatment was significantly higher than the group treated with l-Dopa alone. The
      results of the present study demonstrate that in de novo MPTP parkinsonian
      monkeys antagonizing the action of opioid receptors worsens the motor response to
      l-Dopa.

PMID- 15996566
TI  - S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons
      from human group IIA secretory phospholipase A(2)-induced apoptosis.
AB  - The elevated level of group IIA secretory phospholipase A(2) (sPLA(2)-IIA)
      activity contributes to neurodegeneration in the cerebral cortex after ischemia.
      The up-regulation of cyclooxygenase-2 (COX-2) is also relevant to cerebral
      ischemia in humans. Studies of ischemia with COX-2 inhibitors suggest a clinical
      benefit. In the present study, we investigated effects of S-2474 on sPLA(2)-IIA
      induced cell death in primary cultures of rat cortical neurons, which was
      established as an in vitro model of brain ischemia. S-2474 is a novel
      nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 and contains
      the di-tert-butylphenol antioxidant moiety. S-2474 significantly prevented
      neurons from undergoing sPLA(2)-IIA-induced cell death. S-2474 completely
      ameliorated sPLA(2)-IIA-induced apoptotic features such as the condensation of
      chromatin and the fragmentation of DNA. sPLA(2) also generated neurotoxic
      prostaglandin D(2) (PGD(2)) and free radicals from neurons before cell death. S
      2474 significantly inhibited the sPLA(2)-IIA-induced generation of PGD(2). The
      present cortical cultures contained few non-neuronal cells, indicating that S
      2474 affected neuronal survival directly, but not indirectly via non-neuronal
      cells. The inhibitory effect of S-2474 on COX-2 might contribute to its
      neuroprotective effect. In conclusion, S-2474 exhibits neuroprotective effects
      against sPLA(2)-IIA. Furthermore, the present study suggests that S-2474 may
      possess therapeutic potential for stroke via ameliorating neurodegeneration.

PMID- 15996567
TI  - Cocaine-induced modulation of long-term potentiation in the CA1 region of rat
      hippocampus.
AB  - In order to further characterize the actions of cocaine on synaptic activity in
      the hippocampus, recordings of field excitatory postsynaptic potentials in the
      CA1 region of the rat hippocampal slice preparation were used to monitor drug
      effects on long-term potentiation (LTP) evoked in response to stimulation of the
      Schaffer collateral pathway. Cocaine had dose-dependent, biphasic effects on the
      magnitude of LTP at these excitatory synapses in the stratum radiatum ranging
      from a significant enhancement of LTP at intermediate drug concentrations (5-10
      microM), to an inhibition of LTP at a relatively high drug concentration (30
      microM). The local anesthetic lidocaine had only inhibitory effects on the
      induction of LTP at all concentrations examined (10-75 microM), whereas the
      monoamine transporter antagonists, WIN 35348 (1 microM) or GBR 12935 (5 microM)
      significantly enhanced the magnitude of LTP. The D(2)-like dopamine receptor
      antagonist, eticlopride was effective in preventing this action of cocaine,
      whereas pretreatment with the D(1/5) antagonist, SCH 23390 was ineffective. These
      results suggest that endogenously released dopamine, in the presence of cocaine
      (5-10 microM), can act via D(2)-like receptors to significantly increase the
      magnitude of LTP in the CA1 region of the hippocampus.

PMID- 15996568
TI  - In vivo labelling of alpha5 subunit-containing GABA(A) receptors using the
      selective radioligand [(3)H]L-655,708.
AB  - L-655,708 is an imidazobenzodiazepine possessing 30-70-fold selectivity for the
      benzodiazepine binding site of GABA(A) receptors containing an alpha5 rather than
      alpha1, alpha2 or alpha3 subunit. In the present study, [(3)H]L-655,708 was used
      to label mouse brain benzodiazepine binding sites in vivo. When compared to
      inhibition of in vivo binding of the non-selective ligand [(3)H]Ro 15-1788, the
      pharmacology of mouse in vivo [(3)H]L-655,708 binding was consistent with
      selective in vivo labelling of alpha5 subunit-containing GABA(A) receptors. Thus,
      diazepam was equipotent at inhibiting in vivo [(3)H]L-655,708 and [(3)H]Ro 15
      1788 binding; zolpidem, which has very low affinity for alpha5-containing GABA(A)
      receptors, gave no inhibition of in vivo [(3)H]L-655,708 binding despite
      inhibiting in vivo [(3)H]Ro 15-1788 binding; and L-655,708 was more potent at
      inhibiting the in vivo binding of [(3)H]L-655,708 compared to [(3)H]Ro 15-1788.
      This pharmacological specificity of in vivo [(3)H]L-655,708 binding was confirmed
      autoradiographically. Hence, the anatomical distribution of in vivo [(3)H]L
      655,708 binding was comparable to the distribution of alpha5-containing GABA(A)
      receptors identified in vitro. Moreover, this distribution was distinct from that
      identified using [(3)H]Ro 15-1788. These data therefore suggest that [(3)H]L
      655,708 can be used to identify alpha5-containing GABA(A) receptors in vivo and
      that this ligand can be used to measure receptor occupancy of alpha5-selective
      ligands.

PMID- 15996569
TI  - [Current concepts on the physiopathology of adult-onset Still's disease].
AB  - PURPOSE: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory
      disorder of unknown origin. It is characterized by hectic fever, evanescent rash,
      polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly,
      lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and high serum level
      of ferritin with low glycosylated fraction. CURRENT KNOWLEDGE AND KEY POINTS: An
      increased serum level of ferritin, IL-8, IL-6, IL-18 and TNF-alpha indicates that
      macrophages are highly activated in AOSD. Interleukin 18 (IL-18) seems to be a
      key cytokine in the pathogenesis of AOSD. Serum IL-18 levels are increased in
      AOSD patients compared to other systemic inflammatory diseases such as rheumatoid
      arthritis and they are well correlated with serum ferritin levels and disease
      activity. IL-18 could cause acute liver injury and arthritis. Macrophages could
      be activated by infectious agents such as viruses and by an inadequate control of
      T cell response secondary to depressed Natural Killer lymphocyte function,
      similarly to that observed in systemic juvenile idiopathic arthritis. Sustained
      macrophage activation can lead to the hemophagocytic syndrome, a severe
      complication of both AOSD and systemic juvenile idiopathic arthritis. FUTURE
      PROSPECTS: Cytotoxic cell functions should be probably studied in AOSD as they
      were in the hemophagocytic syndrome and systemic juvenile idiopathic arthritis
      because AOSD, characterised by a marked macrophage activation may be related to
      an immunological deficiency.

PMID- 15996570
TI  - [Auto-immune manifestations in Non-Hodgkin's lymphoma].
AB  - PURPOSE: A wide spectrum of auto-immune manifestations is frequently reported in
      non-Hodgkin's lymphoma (NHL). The purpose of the review is to describe the immune
      manifestations observed in NHL, according to their histological subtype and to
      discuss the current physiopathological hypothesis with their therapeutic
      relevance. CURRENT KNOWLEDGE AND KEY POINTS: Most of the organs can be targeted
      by an immune process due to the lymphoproliferative disease: they include skin
      diseases (paraneoplastic pemphigus, vasculitis, urticaria, acrosyndromes),
      peripheral and central nervous system involvement (polyneuropathy, multifocal
      neuropathy), haematological manifestations (immune cytopenia, acquired bleeding
      disorders), rheumatologic diseases (arthritis, systemic vasculitis, myositis) and
      renal lesion (cryoglobulinemia, glomerulopathies). A higher prevalence of
      autoantibodies, such as antinuclear antibodies, Antiphospholipid antibodies, or
      endomysium antibodies, is observed in NHL but usually without clinical
      manifestations. In B-cell NHL, clinical and biological immune manifestations are
      more frequently observed in indolent lymphoma than in aggressive NHL. In T-cell
      NHL, immune manifestations are frequent and polymorphous, preceding usually the
      diagnosis of lymphoma. The prognosis value of the immune manifestations in NHL is
      unclear. Immune manifestations can be also be related to the treatment procedure,
      including fludarabine, Interferon, autograft or Rituximab. The physiopathology of
      the immune manifestations may involve auto-antibodies production by natural CD5+
      autoreactive B-cell from which is issue the proliferation, a lost of immune
      tolerance, an abnormality in the Fas/Fas Ligand pathway or a chronic antigenic
      stimulation. FUTURE PROSPECTS AND PROJECTS: As observed in T-cell lymphoma cases,
      immunosuppressive treatment can control both immune manifestations and
      lymphoproliferation, suggesting that lymphoma and auto-immunity may be the two
      aspects of the same process. The monoclonal antibody anti-CD20 (rituximab), able
      to suppress the tumoral cells and change the B-cell repertoire is the most
      promising treatment to cure immune disorders related to NHL. So far, rituximab
      has been successfully used in mixed cryoglobulinemia and cold agglutinins
      secondary to NHL.

PMID- 15996571
TI  - [Terminology analysis of the concept of nosocomial infection and proposition of a
      new definition].
AB  - PURPOSE: Nosocomial infection has known many definitions for many years. We
      looked at their terminological validation and proposed a definition that takes
      more into account the defaults that we put in light. METHODS: Our method is a
      terminological one based on analyze of concepts character. RESULTS: Definition of
      nosocomial infection are insufficient and don't take into account characters of
      concepts of "infection" and "nosocomial" and also the possible contaminated
      persons. CONCLUSIONS: We propose a new definition of nosocomial infection and
      hope that we create a debate around it.

PMID- 15996572
TI  - [Electrocardiographic diagnosis. Brugada syndrome].

PMID- 15996573
TI  - [A very purulent lumbar puncture].

PMID- 15996574
TI  - [Association soft tissue sarcoma and familial adenomatous polyposis: a case
      report].

PMID- 15996575
TI  - [Fortuitous diagnosis of Castleman's disease by FDG-PET Scan during the follow-up
      of a renal cancer patient].

PMID- 15996576
TI  - Differences in product information of biopharmaceuticals in the EU and the USA:
      implications for product development.
AB  - The Summary of Product Characteristics (SPC) approved by the European Medicines
      Agency (EMEA) and the Package Insert (PI) approved by the Food and Drug
      Administration (FDA) were examined for 32 biopharmaceutical products. The aim was
      to identify differences in the product information since such information may
      have an impact on the planning of global clinical development programmes. The EU
      SPC contained more detailed instructions to the prescriber, including the
      positioning of the product with regard to the stage of the disease and to other
      therapies. The approach to safety information, notably to contraindications and
      warnings was more conservative in the EU SPC. The conservative approach in the EU
      may reflect the central position of the SPC in risk management of new
      pharmaceuticals. A typical feature of the US PI was the detailed description of
      the efficacy and safety result of the pivotal clinical trials.

PMID- 15996577
TI  - Protein adsorption patterns on poloxamer- and poloxamine-stabilized solid lipid
      nanoparticles (SLN).
AB  - Solid lipid nanoparticles (SLN) were produced using a full range of poloxamer
      polymers and poloxamine 908 for stabilization. The protein adsorption pattern
      acquired on the surface of these particles after intravenous injection is the key
      factor determining the organ distribution. Two-dimensional polyacrylamide gel
      electrophoresis (2-DE) was employed for determination of particle interactions
      with human plasma proteins. The objective of this study was to investigate
      changes in the plasma protein adsorption patterns in the course of variation of
      the polymers stabilizing the SLN. Considerable differences in the protein
      adsorption with regard to preferential adsorbed proteins were detected for the
      different stabilizers. Possible correlations between the polyethylene oxide (PEO)
      chain length and the adsorption of various proteins (first of all
      apolipoproteins) are shown and discussed. Besides the study of protein adsorption
      patterns, the total protein mass adsorbed to the SLN was also evaluated using the
      bicinchoninic acid (BCA)-protein assay. The knowledge concerning the interactions
      of proteins and nanoparticles can be used for a rational development of
      particulate drug carriers. Based on the findings presented in this paper, we
      anticipate that the in vivo well-tolerable SLN are a promising site-specific drug
      delivery system for intravenous injection.

PMID- 15996578
TI  - Silk fibroin as a novel coating material for controlled release of theophylline.
AB  - The aim of this study was to explore potential use of the silk fibroin (SF) as an
      aqueous coating material for theophylline tablets. We have examined the film
      forming and coating properties of heat-treated fibroin, SF solution having
      different amounts of polyethylene glycol (PEG) and 1-ethyl-3-(3-dimethyl
      aminopropyl)carbodiimide (EDC) cross-linked SF. Heat-treated SF material
      possessed a brittle structure, which resulted in poor film forming and coating
      properties. The optimum PEG amount in SF solution was determined as 17% (by
      weight) for an acceptable film forming and zero order release profile. EDC cross
      linked SF has shown a very good film forming and coating property with a
      potential for sustaining the drug release from coated theophylline tablets.
      Dissolution data for coated theophylline tablets were analyzed using Ritger and
      Peppas equation to describe the mechanism of drug release. Drug release from the
      EDC coated tablets followed zero-order kinetics. Release rate constants were
      found to be 0.26, 0.19, 0.16%min(-1) for single-coated, double coated, and triple
      coated tablets, respectively. These results clearly demonstrated that silk
      fibroin has high utility as a novel aqueous coating material for controlled
      release products.

PMID- 15996579
TI  - Poly(ethylene-co-methyl acrylate) membranes as rate-controlling barriers for drug
      delivery systems: characterization, mechanical properties and permeability.
AB  - Poly(ethylene-co-methyl acrylate) (EMA) membranes with different amounts of
      methyl acrylate (MA) content were studied in terms of the thermal and mechanical
      properties, swelling and drug permeation. The increase in MA content in the
      copolymer significantly increased the percentage of elongation and decreased the
      tensile strength and modulus of elasticity of the membranes. The degree of
      swelling of the EMA membranes increased with the ethanol composition and MA
      content. The contact angle of a sessile drop (10 microL of ethanol/water
      solution) decreased with an increase in the ethanol fraction suggesting that the
      membrane wettibility increased with the ethanol content. The flux of diltiazem
      hydrochloride increased from 0.012 to 0.018 mg cm(-2)h(-1) with an increase in
      the MA content from 16.5 to 29.0%. By increasing the ethanol fraction from 0.4 to
      1.0, the flux of diltiazem hydrochloride into the membranes with 29.0% MA,
      increased from 2.56 (+/-0.09) x 10(-3) to 18.38 (+/-0.62) x 10(-3) mg cm(-2)h(
      1). The permeability coefficient increased from 5.85 x 10(-6) to 3.53 x 10(-4) cm
      h(-1) with an increase in the ethanol fraction. The flux can also be correlated
      with the drug solubility in the membrane and ethanol. For example, the
      solubilities of diltiazem hydrochloride, paracetamol and ibuprofen were 0.64,
      6.68 and 504.48 mg cm(-3) in the membrane, respectively. Under the same
      conditions, the flux for the above mentioned drugs was 0.08 (+/-0.01), 0.53 (+/
      0.01) and 45.11 (+/-2.00) mg cm(-2)h(-1).

PMID- 15996580
TI  - Molecular weights of poly(butyl cyanoacrylate) nanoparticles determined by mass
      spectrometry and size exclusion chromatography.
AB  - Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry
      (MALDI-TOF MS) and size exclusion chromatography (SEC) were employed to elucidate
      the chemical composition, mean number average molecular weight (M(n)), mean
      weight average molecular weight (M(w)), and polydispersity (PD) of poly(butyl
      cyanoacrylate) (PBCA) manufactured by emulsion polymerisation. Both methods gave
      similar results for M(n), but substantial differences were observed for M(w) and
      PD, with MALDI producing consistently lower values which could not be improved by
      off-line coupling of SEC and MALDI. MALDI gave a more detailed view on the
      chemical composition of the cyanoacrylate and revealed the presence of two
      additional polymer series with different end groups besides the expected PBCA
      series, which showed different retention in SEC. Their formation is explained by
      the secession/addition of formaldehyde from/to the regular polymer via (reverse)
      Knoevenagel reaction. In additional experiments, the influence of different pH on
      PBCA-NP during polymerisation was examined by comparison of polymerisation yield
      and particle diameter to their chemical composition as revealed by the MALDI
      spectra. The most uniform nanoparticles, with the highest polymerisation yield,
      narrowest particle size, and mass distribution were produced at pH 1.

PMID- 15996582
TI  - Use of CP/MAS solid-state NMR for the characterization of solvate molecules
      within estradiol crystal forms.
AB  - To investigate the solvate molecules within estradiol crystal forms, four crystal
      forms of estradiol (EM, ET, EP and EC) were obtained by recrystallization from
      various organic solvents such as methanol, ethanol, isopropanol and acetone, and
      their physicochemical properties were characterized using XRD, TGA, DSC and solid
      state NMR. The XRD patterns showed that the estradiol crystal forms were composed
      of high crystallinity and their degrees of crystallinity were nearly identical.
      The solvent phases and solvate molecules within the estradiol crystal forms were
      detected by thermal analysis and the solvate molecular structures were identified
      by further observation using solid-state NMR. Estradiol typically tends to
      crystallize in form of its hemihydrate by the solvate molecules from the mother
      solvents used for recrystallization. The residual solvent might be incorporated
      into the estradiol molecules to change the local chemical environment and cause
      the observed 13C CP/MAS NMR spectral changes. These results suggest that the
      thermal analysis and CP/MAS solid-state NMR spectroscopy could be useful at the
      dried solid state to characterize the solvate molecule within the recrystallized
      estradiols.

PMID- 15996581
TI  - Two-month ciprofloxacin implants for multibacterial bone infections.
AB  - A ciprofloxacin implant formulation composed of 12% hydroxyapatite, 36%
      tricalcium phosphate, 12% poly(DL-lactide) (PLA) and 40% ciprofloxacin was
      characterized in vivo for use in treatment of multibacterial bone infection.
      After the implant was inserted in the femur of rabbits, approximately 90% of the
      total ciprofloxacin was released within 8 weeks, maintaining therapeutic levels
      in the femur and tibia. Throughout the femoral cortex and marrow these remained
      higher than the minimum inhibitory concentrations (MIC) against the most common
      pathogens causing osteomyelitis. Levels in tibia cortex were also above MIC for 6
      weeks. The implant was characterized in terms of polymer degradation and
      morphological and crystallographic changes. X-ray analyses confirmed the
      osteoconductivity and biocompatibility of these materials. The sequential changes
      in the femur were those of a normal surgical trauma reaction followed by a repair
      process. All the results confirmed that ciprofloxacin release is limited by its
      low solubility, and that implant erosion and bone ingrowth into the implants
      enhance the antibiotic release.

PMID- 15996583
TI  - The evaluation of the local tolerance of vaginal formulations containing
      dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal
      irritation test.
AB  - The purpose of this study was to evaluate the local tolerance of vaginal gels
      (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug
      Mucosal Irritation test and to compare the results with those of the rabbit
      vaginal irritation test. The irritation potential on the slug mucosa was assessed
      by the mucus production caused by a repeated treatment for 5 successive days.
      Additionally, membrane damage was estimated by the protein and enzyme release. By
      means of a classification prediction model the formulations were classified into
      four irritation classes. The effect of a 10-day intravaginal application of the
      gels on the rabbit vaginal and cervical mucosa was evaluated by means of
      macroscopic and microscopic examination. The placebo and dapivirine gels induced
      no irritation of the slug mucosa (low mucus production and protein release, no
      enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol
      caused severe irritation of the slug mucosa (increased mucus production, protein
      release, and enzyme release) and irritation of the rabbit vagina and cervix. The
      results obtained with the Slug Mucosal Irritation test were comparable to those
      of the rabbit vaginal irritation test.

PMID- 15996584
TI  - The influence of topical formulations on the permeation of 5-aminolevulinic acid
      and its n-butyl ester through excised human stratum corneum.
AB  - The limited permeation of 5-aminolevulinic acid (ALA) through excised human
      stratum corneum could be improved by using 5-aminolevulinic acid-n-butyl ester
      (ABE). Furthermore drug permeation could be increased by choice of a permeation
      enhancing formulation. In this study, permeation of ALA and ABE was investigated
      from various formulations. In addition, differential scanning calorimetry (DSC)
      and wide angle X-ray diffraction (WAXD) experiments were performed in order to
      reveal an interaction between the tested formulations and stratum corneum lipid
      structure. Drug incorporation into Dolgit Mikrogel showed the highest increase in
      permeability with both ALA and ABE. Especially, ABE together with Dolgit Mikrogel
      was the most promising combination. Further permeation studies with poloxamer
      based ABE formulations, partially enriched with ibuprofen acid and medium chained
      triglycerides showed that both compounds promote permeation. The permeation
      coefficients of either drug from Excipial Creme and Basiscreme DAC were found to
      be very similar. These results were in accordance with those of DSC and WAXD
      experiments. Interaction between formulation and stratum corneum lipid structure
      resulting in an increased drug permeation only occurred after pretreatment with
      formulations enriched with ibuprofen acid. After pretreatment with Excipial
      Creme, Basiscreme DAC or Excipial Fettcreme stratum corneum structure and
      subsequently permeability remained unchanged. Nevertheless permeation of ALA from
      Excipial Fettcreme is slower than from the tested hydrophilic formulations and
      therefore believed to be influenced by the affinity of ALA to the vehicle and
      stratum corneum.

PMID- 15996585
TI  - Topical glycerol monooleate/propylene glycol formulations enhance 5
      aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX
      accumulation in hairless mouse skin.
AB  - Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes
      exogenously applied or endogenously formed photosensitizers, further activated by
      light in an appropriate wavelength and dose to induce cell death through free
      radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be
      converted to the effective photosensitizer, protoporphyrin IX (PpIX). However,
      the use of 5-ALA in PDT is limited by the low penetration capacity of this highly
      hydrophilic molecule into appropriate skin layers. In the present study, we
      propose to increase 5-ALA penetration by using formulations containing glycerol
      monooleate (GMO), an interesting and useful component of pharmaceutical
      formulations. Propylene glycol solutions containing different concentrations of
      GMO significantly increased the in vitro skin permeation/retention of 5-ALA in
      comparison to control solutions. In vivo studies also showed increased PpIX
      accumulation in mouse hairless skin, after the use of topical 5-ALA formulations
      containing GMO in a concentration-dependent manner. The results show that skin 5
      ALA penetration and PpIX accumulation, important factors for the success of
      topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol
      formulations.

PMID- 15996586
TI  - Reliability of upper and lower limb three-dimensional kinematics in children with
      hemiplegia.
AB  - The repeatability of both 3D kinematic measurements of arm movement during simple
      upper limb tasks and lower limb movement during gait analysis was evaluated in 10
      children with hemiplegic cerebral palsy. All tasks were completed on two separate
      occasions, 1 week apart. The 3D lower limb gait analysis showed high levels of
      repeatability in the sagittal plane measures, with mean coefficient of multiple
      correlations (CMCs) greater than 0.92 between sessions. Transverse and frontal
      plane measures had mean CMCs greater than 0.7 between sessions. A 3D analysis of
      shoulder and elbow flexion/extension during the two functional tasks (hand to
      head and hand to mouth) was highly repeatable between sessions (mean CMCs, 0.87
      to 0.95). Rotational measures at the shoulder and the elbow during the same tasks
      demonstrated moderate levels of inter-sessional repeatability (mean CMCs shoulder
      0.49 to 0.63; elbow 0.63 to 0.74). Overall, the lower limb 3D kinematic analysis
      had similar levels of repeatability in both the hemiplegic limb and the limb with
      normal tone. The 3D kinematic analysis of movement of the hemiplegic upper limb
      during simple upper limb tasks also had moderate to good repeatability,
      suggesting it may be able to be used as an outcome measure in the hemiplegic
      upper limb.

PMID- 15996587
TI  - The influence of spasticity in the lower limb muscles on gait pattern in children
      with sacral to mid-lumbar myelomeningocele: a gait analysis study.
AB  - Gait analysis and recording of standing position were performed in 38 ambulatory
      children with myelomeningocele. Thirty-four were independent ambulators and four
      required a walking aid. All subjects were assigned one of four muscle function
      groups based on muscle strength. They were also divided into subgroups based on
      the distinction between flaccid and spastic paresis in the lower limb joints. A
      comparison was made between the gait pattern of the children with spasticity and
      that of the children with flaccid paresis in each muscle function group.
      Spasticity in only the ankle joint muscles influenced the subject's gait and
      standing position compared to the subgroups with a flaccid paresis. Even larger
      deviations in gait and standing position were observed when spasticity occurred
      in muscles at the knee and hip joints. When setting ambulatory goals the presence
      of additional neurological symptoms such as spasticity and inadequate balance
      should be taken into consideration.

PMID- 15996588
TI  - Effects of surface irregularity and lighting on step variability during gait: a
      study in healthy young and older women.
AB  - Relatively few studies have examined how uneven surfaces affect human gait. To
      study this, along with the effects of advancing age and low light conditions, we
      measured step width and step time variability, as well as comfortable gait speed,
      in 12 healthy young women (YW) and 12 healthy older women (OW) as they walked at
      a comfortable speed along a 10-m walkway. Ten trials were completed for each cell
      of a 2 x 2 factorial design: (1) flat surface with regular lighting; (2) flat
      surface with low lighting; (3) irregular surface with regular lighting; and (4)
      irregular surface with low lighting. Effects of surface type, incident lighting,
      and age on gait parameters were tested via repeated measures ANOVA. Surface type
      significantly affected step width variability (P < 0.001) and step time
      variability (P < 0.001). Light level showed no significant effect on any of the
      gait parameters. One significant age group difference was found: step width
      variability was significantly greater in OW than YW (P = 0.010). We conclude that
      the irregular surface had a greater effect on the gait variability of healthy OW
      than on that of healthy YW.

PMID- 15996589
TI  - Ground contact characteristics of Tai Chi gait.
AB  - BACKGROUND: To date, no direct measurement has been done that quantitatively
      characterizes the foot-ground contact during Tai Chi Chuan movements. The goal of
      this study was to quantify the biomechanical characteristics of foot-ground
      contact during a Tai Chi gait (TCG), one of the basic but common Tai Chi Chuan
      movements. METHODS: The ground reaction force profiles, center of pressure (COP)
      and plantar pressure patterns under the stance foot of TCG were directly measured
      in a sample of 10 healthy young individuals. RESULTS: The medial force reached a
      peak value of 12 +/- 2% body weight (BW) during early stance. The vertical force
      reached and maintained a peak value of 109 +/- 2% BW during single stance, and
      shifted within a range of 10% and 70% BW during double stance phases. There was a
      uniformly small rate of loading in all three directions throughout stance. The
      peak plantar pressure was fairly constant throughout stance in the rear-foot
      region (maximum value of 0.27 +/- 0.07 kPa/kg), but changed from 0 to 0.16 +/-
      0.04 kPa/kg in the fore-foot region. The peak pressure difference between the
      fore-foot and rear-foot regions was less than 0.06 +/- 0.01 kPa/kg during single
      stance and the second double stance. The maximum plantar contact area during TCG
      was 60 +/- 9% of the foot area. The foot COP displaced largely during the early
      and late part of the stance and maintained fairly stationary during single
      stance. The maximum COP displacement in the medial-lateral direction was 64 +/-
      8% of foot width. CONCLUSIONS: TCG had a low impact force, a fairly evenly
      distributed body weight between the fore-foot and rear-foot regions, and a large
      medial-lateral displacement of the foot COP.

PMID- 15996590
TI  - Influence of an irregular surface and low light on the step variability of
      patients with peripheral neuropathy during level gait.
AB  - Patients with peripheral neuropathy (PN) report greater difficulty walking on
      irregular surfaces with low light (IL) than on flat surfaces with regular
      lighting (FR). We tested the primary hypothesis that older PN patients would
      demonstrate greater step width and step width variability under IL conditions
      than under FR conditions. Forty-two subjects (22 male, 20 female: mean +/- S.D.:
      64.7 +/- 9.8 years) with PN underwent history, physical examination, and
      electrodiagnostic testing. Subjects were asked to walk 10 m at a comfortable
      speed while kinematic and force data were measured at 100 Hz using optoelectronic
      markers and foot switches. Ten trials were conducted under both IL and FR
      conditions. Step width, time, length, and speed were calculated with a MATLAB
      algorithm, with the standard deviation serving as the measure of variability. The
      results showed that under IL, as compared to FR, conditions subjects demonstrated
      greater step width (197.1 +/- 40.8 mm versus 180.5 +/- 32.4 mm; P < 0.001) and
      step width variability (40.4 +/- 9.0 mm versus 34.5 +/- 8.4 mm; P < 0.001), step
      time and its variability (P < 0.001 and P = 0.003, respectively), and step length
      variability (P < 0.001). Average step length and gait speed decreased under IL
      conditions (P < 0.001 for both). Step width variability and step time variability
      correlated best under IL conditions with a clinical measure of PN severity and
      fall history, respectively. We conclude that IL conditions cause PN patients to
      increase the variability of their step width and other gait parameters.

PMID- 15996591
TI  - Reliability of the long-range power-law correlations obtained from the bilateral
      stride intervals in asymptomatic volunteers whilst treadmill walking.
AB  - Stride intervals measured during steady-state walking are irregular. These stride
      interval fluctuations are not random but exhibit long-range power-law correlation
      (alpha) such that a given stride interval is 'influenced' by earlier variations
      in the stride intervals. To estimate alpha, one requires a minute long sequence
      of right or left side stride interval data. However, to obtain a reliable alpha
      point estimate, the minimal stride sequence length is unknown. Additionally, it
      is unknown if the right and left side alpha are equivalent. In this study, the
      within-day and the right and left side reliabilities of alpha point estimates
      were examined in 23 volunteers performing three 8-min treadmill walks. In
      addition, eight volunteers were retested on three additional days to estimate
      between-day reliability. The standard error of measurement (S.E.M.) and the
      within- and between-day intraclass correlation (ICC) values, and their 95%
      confidence intervals, each calculated using the combined right and left leg 8-min
      alpha estimates were acceptable [0.047 (0.044-0.051); 0.914 (0.882-0.932) and
      0.769 (0.689-0.815), respectively]. The left alpha (0.688 +/- 0.93) was greater
      than the right alpha (0.664 +/- 0.094), albeit this finding was underpowered
      (0.55). The alpha point estimates obtained from the full 8-min walks provided
      minimal S.E.M. and maximal within- and between-day ICCs. However, the minimal
      S.E.M. was statistically indistinguishable from the 6- and 7-min walk durations
      and all of the within-day and between-day ICCs were similar except for the 3- and
      8-min between-day ICCs. This study suggests that data from four 3 min, three 6
      min or two 8 min walk duration trials provide reliable alpha point estimates from
      a short series of short treadmill walks.

PMID- 15996592
TI  - Gait differences between individuals with post-stroke hemiparesis and non
      disabled controls at matched speeds.
AB  - Treadmill walking was used to assess the consistent gait differences between six
      individuals with post-stroke hemiparesis and six non-disabled, healthy controls
      at matched speeds. The hemiparetic subjects walked on the treadmill at their
      comfortable speeds, while each control walked at the same speed as the
      hemiparetic subject with whom he or she was matched. Kinematic and insole
      pressure data were collected from multiple, steady-state gait cycles. A large set
      of gait differences found between hemiparetic and non-disabled subjects was
      consistent with impaired swing initiation in the paretic limb (i.e., inadequate
      propulsion of the leg during pre-swing, increased percentage swing time, and
      reduced knee flexion at toe-off and mid-swing in the paretic limb) and related
      compensatory strategies (i.e., pelvic hiking and swing-phase propulsion and
      circumduction of the paretic limb). Exaggerated positive work associated with
      raising the trunk during pre-swing and swing of the paretic limb, consistent with
      pelvic hiking, contributed to increased mechanical energetic cost during walking.
      A second set of gait differences found was consistent with impaired single limb
      support on the paretic limb (i.e., shortened support time on the paretic limb)
      and related compensatory strategies (i.e., exaggerated propulsion of the non
      paretic limb during pre-swing to shorten its swing time). Other significant gait
      differences included asymmetry in step length and increased step width. We
      conclude that consistent gait differences exist between hemiparetic and non
      disabled subjects walking at matched speeds. The differences provide insights,
      concerning hemiparetic impairment and related compensatory strategies, that are
      in addition to the observation of slow walking speed.

PMID- 15996593
TI  - Gait deviations associated with post-stroke hemiparesis: improvement during
      treadmill walking using weight support, speed, support stiffness, and handrail
      hold.
AB  - By comparing treadmill walking in hemiparetic and non-disabled individuals at
      matched speeds, Chen et al. [Chen G, Patten C, Kothari DH, Zajac FE. Gait
      differences between individuals with post-stroke hemiparesis and non-disabled
      controls at matched speeds. Gait Posture (2004)] identified gait deviations that
      were consistent with impaired swing initiation and single limb support in the
      paretic limb and related compensatory strategies. Treadmill training with harness
      support is a promising, task-oriented approach to restoring locomotor function in
      individuals with post-stroke hemiparesis. To provide a rationale for the proper
      selection of training parameters, we assessed the potential of body weight
      support, treadmill speed, support stiffness, and handrail hold to improve the
      identified gait deviations associated with hemiparesis during treadmill walking.
      In the six hemiparetic subjects studied, the adjustment of each training
      parameter was found to improve a specific set of the gait deviations. With
      increased body weight support or the addition of handrail hold, percentage single
      limb support time on the paretic limb increased and temporal symmetry improved.
      With increased treadmill speed, leg kinetic energy at toe-off in the paretic limb
      increased but remained low relative to values in the non-paretic limb. With
      increased support stiffness, the exaggerated energy cost associated with raising
      the trunk during pre-swing and swing of the paretic limb was improved. We
      conclude that the proper selection of training parameters can improve the gait
      pattern practiced by individuals with hemiparesis during treadmill training and
      may improve treatment outcome.

PMID- 15996594
TI  - Influence of load and carrying methods on gait phase and ground reactions in
      children's stair walking.
AB  - The study investigated the effects of carrying methods and loads on gait phase
      and ground reaction force during stair ascent and descent in children. The
      carrying methods that were examined included the backpack and one-strap athletic
      bag. The load weights included 0%, 10%, 15%, and 20% of body weight. Thirteen
      school children aged 12.21 +/- 0.98 years were recruited as subjects. A Novel
      Pedar System was used to record and analyze the insole pressure during stair
      walking with different loads. The load that caused a significant increase in the
      peak force in each bag and stair mode was 15% of body weight, except for stair
      ascent carrying the athletic bag, where the load was 10% of body weight. The
      maximum peak force that was induced by this load in stair descent was 1.25 times
      that in descent with no load, 1.89 times that in ascent with the same load, and
      2.19 times that in ascent with no load. The force-to-time ratio in descent was
      about three times that in ascent.

PMID- 15996595
TI  - Central somatosensory changes and altered muscle synergies in subjects with
      anterior cruciate ligament deficiency.
AB  - To clarify the mechanisms of compensation in subjects with anterior cruciate
      ligament deficiency (ACL-D), we examined proprioception, quadriceps strength,
      somatosensory evoked potentials (SEPs) and muscle responses during gait in varied
      combinations of speed and incline. Seventeen subjects with ACL-D were grouped by
      functional level and report of giving way. Seven subjects without ACL-D served as
      a control sample for muscle response measures. ACL-D subjects with quadriceps
      weakness experienced giving way and could not resume sport activities. Those
      without weakness fell into one of two groups: (1) copers, who had full return to
      previous activity and no giving way despite proprioceptive loss and altered SEPs,
      and (2) adapters, who were unable to return to previous activity level and
      experienced giving way despite neither proprioceptive loss or altered SEPs. The
      unique muscle pattern in copers during inclined fast walking included larger and
      earlier hamstring activation. These results suggest that in individuals with ACL
      D without a strength deficit, altered SEPs and altered neuromuscular patterns are
      the factors that enable resumption of pre-injury functional levels. Loss of
      proprioception may drive the central changes, which in turn drives the
      development of altered muscle patterns.

PMID- 15996596
TI  - Effects of physical activity level on unobstructed and obstructed walking in
      young male adults.
AB  - Physical activity levels vary across the general population due to lifestyles and
      work habits. The goal of the present study was to compare the locomotor behavior
      between active and inactive young male subjects during unobstructed and
      obstructed walking. Eight active and eight inactive adult male subjects from 22
      to 44 years old participated in the study. Three walking conditions at natural
      speed were studied including: level walking, avoidance of a moderately high
      obstacle set to 10% of the subject's lower limb length and avoidance of a high
      obstacle set to 30% of the subject's lower limb length. Kinematic and inverse
      dynamic analyses were performed to detail the locomotor strategies in the
      sagittal plane. Active subjects walked faster than the inactive subjects during
      both level walking and when crossing the obstacles with the lead limb. During
      trail limb avoidance, there were no differences between groups for gait speed.
      The analysis of mechanical power showed that the same general lower limb
      strategies were used by both groups, although specific differences related to the
      kinematic changes were found across conditions. The results show that, although
      general locomotor strategies are the same for active and inactive young adults,
      locomotor behavior is not homogeneous.

PMID- 15996597
TI  - Comparison of utilized coefficient of friction during different walking tasks in
      persons with and without a disability.
AB  - The purpose of this study was to determine if older persons with a disability
      have greater utilized coefficient of friction requirements than healthy older and
      younger adults during various walking conditions. Forty-eight community-dwelling
      adults were divided into five groups based on medical diagnosis and age: CVA
      (unilateral stroke; mean age 63 years), DM (diabetes mellitus; mean age 70
      years), ARTH (lower extremity arthritis; mean age 69 years), SENIOR (healthy;
      mean age 73 years), and YOUNG (healthy; mean age 29 years). Ground reaction
      forces (GRF) were recorded as subjects walked across a walkway, ascended and
      descended stairs, and negotiated a turn. The utilized coefficient of friction
      (COF(U)) throughout stance was calculated as the ratio of shear to vertical GRFs,
      and the peak COF(U) resulting from a shear force that would contribute to a
      forward foot slip was identified. Separate one-way ANOVAs were used to identify
      differences in peak COF(U) across subject groups for each walking task. The
      results of this study found that for all conditions evaluated, those with a
      disability did not demonstrate greater friction requirements then adults without
      a disability. Friction requirements for the YOUNG group were significantly
      greater than all disability groups while negotiating a turn, and were greater
      than the DM group during level walking. These results indicated that the
      diagnostic groups evaluated in this study are not at any greater risk for slip
      initiation than the healthy older or younger adults during the tasks evaluated.

PMID- 15996599
TI  - The future of endovascular aneurysm repair.

PMID- 15996600
TI  - The methylenetetrahydrofolate reductase C677T polymorphism does not associate
      with susceptibility to abdominal aortic aneurysm.
AB  - OBJECTIVES: To test whether the T variant of the C677T polymorphism in the gene
      for 5,10-methylenetetrahydrofolate reductase (MTHFR) would associate with three
      distinct forms of vascular disease, abdominal aortic aneurysm (AAA), coronary
      artery disease (CAD) and peripheral vascular disease (PVD). BACKGROUND: Increases
      in homocysteine induce elastolytic activity in the arterial wall, a condition
      which may favour vascular pathogenesis including aneurysm formation. Homozygosity
      of the common T variant of the C677T polymorphism in the gene for MTHFR has been
      shown to associate with increased levels of homocysteine. Thus, this functional
      polymorphism may lead to an increased propensity to develop cardiovascular
      disease and, in particular, AAA. METHODS: An association study was conducted
      across 1207 subjects; 428 patients with AAA, 271 CAD patients, 226 PVD patients
      and 282 controls being genotyped for the C667T variants of MTHFR. RESULTS: There
      were no significant differences in the frequency of the MTHFR C677T variant
      between any of the groups examined. AAA patients who were homozygotes for the
      677T allele did, however, appear to have significantly larger aneurysms than C
      allele carriers. CONCLUSION: This study provides no evidence that the T variant
      of MTHFR is associated with susceptibility to AAA, CAD or PVD. It may, however,
      be a contributory factor in AAA severity as indicated by aneurysm size.

PMID- 15996601
TI  - Experiences of intentional carotid stenting in endovascular repair of aortic arch
      aneurysms--two case reports.
AB  - Endovascular repair of thoracic aneurysms has emerged as an attractive
      alternative especially in patients at high risk. However, the left common carotid
      artery limits the use of stent-grafts in aneurysms located in the aortic arch or
      close to the left subclavian artery. We report two cases with aneurysms in the
      distal arch and proximal descending aorta, where we have used a carotid stent in
      juxtaposition to an aortic stent-graft, to gain a longer proximal neck in the
      aortic arch in an attempt not to rely only on a by-pass graft feeding the left
      carotid artery.

PMID- 15996602
TI  - Risk of major haemorrhage in patients after infrainguinal venous bypass surgery:
      therapeutic consequences? The Dutch BOA (Bypass Oral Anticoagulants or Aspirin)
      Study.
AB  - OBJECTIVES: The beneficial effect of oral anticoagulants after infrainguinal
      venous bypass surgery is compromised by bleeding complications. We developed a
      model to identify patients, treated with anticoagulation, at risk of major
      haemorrhage and estimated whether this complication could have been prevented if
      patients had received aspirin. DESIGN: Randomised clinical trial. METHODS: Data
      of patients who participated in the Dutch Bypass Oral Anticoagulation or Aspirin
      Study were reanalysed using Cox regression. After infrainguinal bypass surgery
      these patients were randomised to oral anticoagulants (n = 1326) or aspirin (n =
      1324). RESULTS: Predictors of major haemorrhage for patients on oral
      anticoagulants were increased systolic blood pressure (> or = 140 mmHg, hazard
      ratio [HR] 1.62), age > or = 75 years (HR 2.77) and diabetes mellitus (HR 1.60).
      If the 345 patients in the highest risk quartile had received aspirin, major
      haemorrhages would have been reduced from 46 to 22, with no major changes in
      ischemic events and graft occlusions. In the subgroup with venous bypasses major
      haemorrhages would have been reduced from 27 to 13, at the cost of seven more
      ischemic events (mostly fatal) and 17 more graft occlusions. CONCLUSIONS:
      Treating patients at highest risk of major haemorrhage with aspirin instead of
      oral anticoagulants would have resulted in a reduction of non-fatal haemorrhages,
      but for venous bypasses this reduction was outweighed by an increase in ischemic
      events and graft occlusions. We still recommend treatment with oral
      anticoagulants after peripheral venous bypass surgery.

PMID- 15996603
TI  - Comparison of the prevalence of APC-resistance in vascular patients and in a
      normal population cohort in Western Germany.
AB  - OBJECTIVE: To compare the prevalence of APC-resistance (APC-R) in patients with
      peripheral vascular disease and the general population. DESIGN: Prospective
      cohort examination. MATERIALS AND METHODS: Three hundred and eleven patients
      (group A) suffering from arterial occlusive disease or an abdominal aortic
      aneurysm were prospectively screened for APC-R. There were 228 men and 83 women
      with a mean age of 65 years (20-88 years). Two hundred and sixty patients
      underwent an open surgical or interventional procedure. A total of 306 patients
      were followed clinically for an average of 8 months (1-31 months). Two hundred
      and seven healthy volunteers (group B) served as a control group. RESULTS: The
      prevalence of a functional APC-R was 11% (33/311) and 8% in groups A and B,
      respectively, (p = 0.272). APC-R did not occur more frequently among patients who
      were treated primarily for a bypass occlusion (3/21 vs 30/290) (p = 0.476). None
      of five patients who had a postinterventional graft or vessel occlusion (1.9%)
      had an APC-R. Sixteen patients (5%) experienced an arterial occlusion during
      follow-up of which two had APC-R. CONCLUSIONS: Previously published increased
      prevalence rates of APC-R in patients with arterial disorders could not be
      confirmed in this study. A firm association between the presence of APC-R and
      previous bypass occlusion or postoperative failure of the vascular reconstruction
      could not be demonstrated.

PMID- 15996604
TI  - It is time for physicians to embrace cost-effectiveness and cost utility analysis
      research in the treatment of spinal pain.

PMID- 15996605
TI  - Cost-based evaluations of the treatment of back pain: a primer for health-care
      professionals.
AB  - BACKGROUND CONTEXT: There is an extensive literature on the costs of back pain
      and on cost-based evaluations of the effectiveness of alternative modes of care
      for back pain. An understanding of the adequacy of a study often requires
      information that is not part of the experience or training of health-care
      professionals. The article seeks to provide clinicians with some criteria by
      which to judge the validity of cost-based evaluations of the treatment and
      consequences of back pain. PURPOSE: This article is not a comprehensive, critical
      review of the research literature on the costs of back pain or the relative cost
      effectiveness of different methods of care for back pain. It presents, instead, a
      discussion of some important characteristics of cost-related studies of back pain
      and some criteria that can be used to evaluate the validity of cost estimates and
      cost-effectiveness analyses related to back pain. STUDY DESIGN: A guide for the
      evaluation of cost-based studies of back pain. METHODS: A summary of criteria for
      the evaluation of the validity of cost-based studies of back pain. RESULTS: Three
      sets of criteria for evaluation, ranked from most important to least important.
      CONCLUSIONS: Application of the suggested criteria can enhance the ability of
      health-care professionals to better understand the limits and relative adequacy
      of cost-based studies of back pain.

PMID- 15996606
TI  - Centralization as a predictor of provocation discography results in chronic low
      back pain, and the influence of disability and distress on diagnostic power.
AB  - BACKGROUND CONTEXT: The "centralization phenomenon" (CP) is the progressive
      retreat of referred pain towards the spinal midline in response to repeated
      movement testing (a McKenzie evaluation). A previous study suggested that it may
      have utility in the clinical diagnosis of discogenic pain and may assist patient
      selection for discography and specific treatments for disc pain. PURPOSE:
      Estimation of the diagnostic predictive power of centralization and the influence
      of disability and patient distress on diagnostic performance, using provocation
      discography as a criterion standard for diagnosis, in chronic low back pain
      patients. STUDY DESIGN/SETTING: This study was a prospective, blinded,
      concurrent, reference standard-related validity design carried out in a private
      radiology clinic specializing in diagnosis of chronic spinal pain. PATIENT
      SAMPLE: Consecutive patients with persistent low back pain were referred to the
      study clinic by orthopedists and other medical specialists for interventional
      radiological diagnostic procedures. Patients were typically disabled and
      displayed high levels of psychosocial distress. The sample included patients with
      previous lumbar surgery, and most had unsuccessful conservative therapies
      previously. OUTCOME MEASURES:  DIAGNOSIS: results of provocation discography.
      INDEX TEST: The CP. Psychometric evaluation: Roland-Morris, Zung, Modified
      Somatic Perception questionnaires, Distress Risk Assessment Method, and 100-mm
      visual analog scales for pain intensity. METHODS: Patients received a single
      physical therapy examination, followed by lumbar provocation discography.
      Sensitivity, specificity, and likelihood ratios of the CP were estimated in the
      group as a whole and in subgroups defined by psychometric measures. RESULTS: A
      total of 107 patients received the clinical examination and discography at two or
      more levels and post-discography computed tomography. Thirty-eight could not
      tolerate a full physical examination and were excluded from the main analysis.
      Disability and pain intensity ratings were high, and distress was common.
      Sensitivity, specificity, and positive likelihood ratios for centralization
      observed during repeated movement testing for pain distribution and intensity
      changes were 40%, 94%, and 6.9 respectively. In the presence of severe
      disability, sensitivity, specificity, and positive likelihood ratios were 46%,
      80%, 3.2 and for distress, 45%, 89%, 4.1. In the subgroups with moderate,
      minimal, or no disability, sensitivity and specificity were 37%, 100% and for no
      or minimal distress 35%, 100%. CONCLUSIONS: Centralization is highly specific to
      positive discography but specificity is reduced in the presence of severe
      disability or psychosocial distress.

PMID- 15996607
TI  - Provocative cervical discography symptom mapping.
AB  - BACKGROUND CONTEXT: In a small prospective study assessing 10 symptomatic and 10
      asymptomatic subjects, Schellhas et al. compared cervical discography to magnetic
      resonance imaging. Within that study he reported on the distribution of pain for
      the C3-C4 to C6-C7 levels. Four years later, Grubb and Ellis reported
      retrospective data from his 12-year experience using cervical discography from C2
      C3 to C7-T1 in 173 patients. To date, no large prospective study defining pain
      referral patterns for each cervical disc has been performed. PURPOSE: To conduct
      a prospective visual and statistical descriptive study of pain provocation of a
      cohort of subjects undergoing cervical discography. STUDY DESIGN/SETTING:
      Prospective multicenter descriptive study. METHODS: Pain referral maps were
      generated for each disc level from patients undergoing cervical discography with
      at least two levels assessed. If concordant pain was reproduced in a
      morphologically abnormal disc, the subject immediately completed a pain diagram.
      An independent observer interviewed the subject and recorded the location of
      provoked symptoms. Visual data were compiled using a body sector bit map, which
      consisted of 48 clinically relevant body regions. Visual maps with graduated
      color codes and frequencies of symptom location at each cervical disc level were
      generated. RESULTS: A total of 101 symptom provocation maps were recorded during
      cervical discography on 41 subjects. There were 10 at C2-C3, 19 at C3-C4, 27 at
      C4-C5, 27 at C5-C6, 16 at C6-C7 and 2 at C7-T1. Predominantly unilateral symptoms
      were provoked just as often as bilateral symptoms. The C2-C3 disc referred pain
      to the neck, subocciput and face. The C3-C4 disc referred pain to the neck,
      subocciput, trapezius, anterior neck, face, shoulder, interscapular and limb. The
      C4-C5 disc referred pain to the neck, shoulder, interscapular, trapezius,
      extremity, face, chest and subocciput. The C5-C6 disc referred pain to the neck,
      trapezius, interscapular, suboccipital, anterior neck, chest and face. The C6-C7
      disc referred pain to the neck, interscapular, trapezius, shoulder, extremity and
      subocciput. At C7-T1 we produced neck and interscapular pain. Visual maps with
      graduated color codes and frequencies of symptom location at each cervical disc
      level were generated. CONCLUSIONS: In conclusion, these results confirm the
      observations of prior investigators that cervical internal disc disruption can
      elicit axial and peripheral symptoms. The particular patterns of pain generation
      allow the discographer to preprocedurally anticipate disc levels to assess. With
      these data, the number of disc punctures that are required can be limited rather
      than routinely assessing all cervical discs.

PMID- 15996608
TI  - Comparison of discographic findings in asymptomatic subject discs and the
      negative discs of chronic LBP patients: can discography distinguish asymptomatic
      discs among morphologically abnormal discs?
AB  - BACKGROUND CONTEXT: Lumbar discography has been widely used for evaluating
      discogenic low back pain (LBP). Comparison of pain responses from suspected
      symptomatic discs with pain responses from asymptomatic negative discs is
      routine. However, the ability of discography to distinguish asymptomatic
      morphologically abnormal discs from those that are symptomatic has been
      understudied. In addition, the discographic characteristics of negative discs in
      patients with chronic discogenic LBP have not been reported. Criteria for
      negative morphologically abnormal discs may be valuable for excluding discs from
      further treatment and examination. PURPOSE: To determine if discography can
      distinguish asymptomatic discs among morphologically abnormal discs in patients
      with suspected chronic discogenic LBP and establish the standard characteristics
      of negative discs. STUDY DESIGN/SETTING: Prospective, experimental with control
      group. PATIENT SAMPLE: Fifty-five discs from a control group of 16 healthy
      volunteers without current back pain (11 men, 5 women, 32-61 years of age, mean
      age: 47 years) and 282 discs from a patient group of 90 LBP patients (59 men, 31
      women, 20-70 years of age, mean age: 44.7 years) were recruited. METHODS:
      Discography was performed using a pressure-controlled manometric technique with
      an injection rate of 0.05 mL/s and a 3.5 mL restricted total volume. Concordance
      was rated as none/unfamiliar, or familiar. Pain was rated via a 0-10 numerical
      rating scale (NRS). The pressure and volume at which pain was evoked and NRS pain
      responses at 15, 30, and 50 psi were recorded. Annular disruption grade was rated
      during the procedure by computed tomography discography and fluoroscopic imaging.
      Negative discogram required no pain described by the participant as "familiar,"
      with no pain responses >or=6/10 NRS at pressures <or=50 psi above opening
      pressure and <or=3.5 mL total injected volume. Patient discs were partitioned
      into two subgroups based on discographic findings: Neg-D (negative discs) and Pos
      D (positive discs). Only discs with Grade 3 annular tears (Dallas Discogram
      Scale) were included in the study. RESULTS: Among 55 asymptomatic control group
      discs, 32 (58.2%) exhibited Grade 3 annular tear. All discs in the asymptomatic
      control group satisfied negative response criteria. Among 282 patient group
      discs, 199 (70.6%) exhibited Grade 3 annular tear. Of 199 discs with Grade 3
      annular tears, 104 (52.3%) satisfied negative response criteria and were
      categorized as the Neg-D group. The other 95 discs were categorized as a Pos-D
      group. Patients showed significantly lower pain tolerance relative to control
      subjects (p<.05). The control and Neg-D groups showed similar pressures and
      volumes at which pain was initially evoked. Mean control group pain scores were
      0.47 NRS at 15 psi and 1.58 NRS at 50 psi. Mean Neg-D group pain scores were 0.11
      NRS at 15 psi and 1.1 NRS at 50 psi. Discographic findings for the Pos-D group
      were significantly different from those of the control and Neg-D groups (p<.001).
      CONCLUSIONS: Pain tolerance was significantly lower in patients relative to
      asymptomatic subjects. Negative patient discs and asymptomatic subject discs
      showed similar characteristics. Pressure-controlled manometric discography using
      strict criteria may distinguish asymptomatic discs among morphologically abnormal
      discs with Grade 3 annular tears in patients with suspected chronic discogenic
      LBP.

PMID- 15996609
TI  - Treating acute low back pain with continuous low-level heat wrap therapy and/or
      exercise: a randomized controlled trial.
AB  - BACKGROUND CONTEXT: Restorative exercise and palliative modalities are frequently
      used together for the treatment of acute low back pain. However, little is known
      about the effects of combining these treatments. PURPOSE: To evaluate the
      efficacy of combining continuous low-level heat wrap therapy with directional
      preference-based exercise on the functional ability of patients with acute low
      back pain. STUDY DESIGN/SETTING: A randomized controlled trial was conducted at
      three outpatient medical facilities. PATIENT SAMPLE: One hundred individuals (age
      31.2+/-10.6 years) with low back pain of less than 3 months duration. OUTCOME
      MEASURES: The primary outcome measure was functional ability assessed by the
      Multidimensional Task Ability Profile questionnaire. Secondary outcomes were
      disability assessed by the Roland-Morris Disability Questionnaire and pain relief
      assessed by a 6-point verbal rating scale. METHODS: Participants were randomized
      to one of four groups: Heat wrap therapy alone (heat wrap, n=25); directional
      preference-based exercise alone (exercise, n=25); combination of heat wrap
      therapy and exercise (heat+exercise, n=24); or control (booklet, n=26). Treatment
      was administered for five consecutive days and included four visits to the study
      center over 1 week. RESULTS: At 2 days after the conclusion of treatment (Day 7),
      functional improvement for heat+exercise was 84%, 95%, and 175% greater than heat
      wrap, exercise, and booklet, respectively (p<.05). Seventy-two percent of the
      subjects in the heat+exercise group demonstrated a return to pre-injury function
      compared with 20%, 20%, and 19% for heat wrap, exercise, and booklet,
      respectively (p<.05). Disability reduction for heat+exercise was 93%, 139%, and
      400% greater than heat wrap, exercise, and booklet, respectively (p<.05). Pain
      relief for heat+exercise was 70% and 143% greater than exercise and booklet,
      respectively (p<.05). CONCLUSIONS: Combining continuous low-level heat wrap
      therapy with directional preference-based exercise during the treatment of acute
      low back pain significantly improves functional outcomes compared with either
      intervention alone or control. Either intervention alone tends to be more
      effective than control.

PMID- 15996610
TI  - On the diagnosis of malingered pain-related disability: lessons from cognitive
      malingering research.
AB  - BACKGROUND CONTEXT: Pain-related disability is a complex phenomenon. Malingering
      is a potential factor in the management of patients with pain. Methodological
      problems and inappropriate expectations regarding diagnostic accuracy have
      hampered the study of malingering detection in pain. In contrast, the study of
      cognitive malingering in neuropsychology has led to the development of many
      highly accurate and reliable detection techniques. This paper applies the methods
      and logic that have been successful for identifying cognitive malingering to the
      problem of malingering in patients with pain. PURPOSE: Outline the logic of a
      research methodology for studying malingering detection in pain and introduce a
      system for the diagnosis of malingering in pain. STUDY DESIGN: Literature review
      and conceptual synthesis. METHODS: Examination of the research methodology and
      diagnostic scheme used in the study of cognitive malingering; adaptation of these
      methods to the problem of malingering in pain. RESULTS: Lessons derived from the
      study of cognitive malingering were used to generate recommendations to enhance
      research into detection and diagnosis of malingered pain-related disability. A
      comprehensive, multidimensional system for diagnosing malingering in pain-related
      disability was proposed. CONCLUSIONS: Pain-related disability is a multifaceted
      phenomenon, therefore malingering can occur in different and sometimes multiple
      dimensions. It is presently possible to accurately detect and diagnose
      malingering in some patients with pain. More work is needed for some detection
      techniques to be appropriately calibrated in pain populations. This work must
      focus on controlling the false positive error rate.

PMID- 15996611
TI  - External fixation for dynamic correction of severe scoliosis.
AB  - BACKGROUND CONTEXT: The ideal treatment for scoliosis may be the correction of
      the factors that cause the disease. An external fixation device was used in 12
      patients to achieve a correction by dynamic distraction, compression and
      derotation of the curve. Follow-up was done over a 7-year period. PURPOSE: To
      describe the treatment of inflexible and severe scoliosis by special correction
      with external fixation. STUDY DESIGN/SETTING: This was a prospective,
      longitudinal and descriptive study, with a follow-up period of 7 years. PATIENT
      SAMPLE: Twelve patients (9 female, 3 male) from the National Orthopaedic
      Institute Spine Service in external consultation. OUTCOME MEASURES: Radiographic
      measurements with the scoliosis angulation of Cobb's method were used before
      surgery, after surgery and in the final follow-up period. METHODS: The surgical
      procedure consisted of two stages, anterior and posterior approach, dissectomies,
      vertebrectomy at the apex, spinal column shortening and the placement of an
      external stabilization device. Progressive correction of the curve was done by a
      daily increase in distraction (3 mm/day). When the correction was finished, a
      different internal fixation device was used to maintain the correction. The time
      between initial treatment and final correction was 50 days. Ten thoracic curves,
      one thoracolumbar curve and one lumbar curve were treated, with an average of 93
      degrees. All patients had kyphosis with an average of 89 degrees. Vertebral
      rotation was not found in two patients. RESULTS: Average correction of scoliosis
      was 52.9% and of kyphosis, 29%. Vertebral rotation in eight cases was corrected.
      There were no neurological irreversible lesions in any patient. There was one
      infection. Using an evaluation result scale, there were 2 excellent, 6 good and 4
      fair outcomes. The average loss of correction was 5 degrees. CONCLUSION: The
      results suggest that the use of an external stabilization device with controlled
      compression on the convexity and distraction on the concavity of the curve can
      achieve a correction of up to 50% in scoliosis, 30% in kyphosis and 1 degree in
      the rotation of the spine.

PMID- 15996612
TI  - Influence of structural pelvic disorders during standing and walking in
      adolescents with idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: In adolescents with idiopathic scoliosis (AIS), several
      studies have shown that the pelvis is structurally changed by the spinal
      disorder. In fact, a significant correlation has been observed between the three
      dimensional changes in the lumbar curve and the reduction in pelvic displacement
      in the three spatial planes during gait. However, the impact of this pelvic
      disorder on the walking mechanism has not been established. PURPOSE: To
      quantitatively evaluate the influence of scoliosis on the three-dimensional (3D)
      pelvic position during bipedal standing, on the 3D pelvic displacement during
      gait, and on the walking mechanics in adolescents with idiopathic lumbar and
      thoraco-lumbar scoliosis. STUDY DESIGN/SETTING: Paired sample matched for age and
      gender. PATIENT SAMPLE: Twenty-four subjects, 12 healthy adolescents matched for
      age and gender with 12 adolescents with lumbar or thoraco-lumbar idiopathic
      scoliosis. OUTCOME MEASURES: A test battery including clinical examination,
      radiological assessment, static 3D pelvic examination in bipedal position, and
      instrumented gait analysis. The statistical analysis was performed by a paired t
      test to evaluate the differences on nominally recorded data between control
      subjects and patients and a signed rank test for ordinal data. METHODS: The spine
      and pelvis were assessed by X-ray, clinical examination, and 3D analysis with the
      Elite system V5, in the standing position. The gait was assessed by instrumented
      analysis, including synchronous kinematic, dynamic, and electromyographic (EMG)
      recordings. RESULTS: Our results showed that radiological measurements of the
      pelvis were significantly different between patients and control subjects.
      However, 3D pelvic kinematics were not significantly different between AIS
      patients and normal subjects during standing and walking. We observed an increase
      in the muscular external work, a reduction in the efficiency of the locomotor
      mechanism, and a prolonged duration of activation of the lumbar muscles, ie,
      erector spinae and quadratum lumborum, in AIS patients. CONCLUSIONS: The
      scoliosis affected the structural bones of the pelvis with no effect on the 3D
      pelvis position during standing. During walking, normal 3D pelvic displacements
      could be explained by the prolonged duration of activation of the erector spinae
      and quadratum lumborum muscles bilaterally allowing the equilibrium of the pelvis
      to be maintained. This excessive muscular activity caused a failure of the
      locomotor mechanism as shown by an increase in the muscular external work.

PMID- 15996613
TI  - Value of intraoperative true lateral radiograph of C2 pedicle for C1-2
      transarticular screw insertion.
AB  - BACKGROUND CONTEXT: Transarticular C1-2 screws are widely used in posterior
      cervical spine instrumentation. Injury to the vertebral artery during insertion
      of transarticular Cl-2 screw remains a serious complication. Use of a computer
      assisted surgery system decreases this complication considerably. However, this
      system encounters problems in ensuring complete accuracy because of positional
      variations during preoperative and intraoperative imaging generation. Therefore,
      intraoperative fluoroscopy still is one of the commonly used methods to guide
      insertion of transarticular Cl-2 screw. Evaluation of a true lateral radiographic
      view of the C2 pedicle for screw trajectory during C1-2 transarticular screw
      insertion may help to minimize this potential complication. PURPOSE: To evaluate
      the value of intraoperative true lateral radiograph of the C2 pedicle for screw
      trajectory during C1-2 transarticular screw insertion. STUDY DESIGN: To compare
      the height of the C2 pedicle area allowing instrumentation on true lateral view
      radiograph of the C2 pedicle and computed tomographic (CT) scan with multiplanar
      reconstruction. METHODS: Twenty embalmed human cadaveric cervical spine specimens
      were used to insert a total of 40 C1-2 transarticular screws using Magerl and
      Seemann technique. One side of the C2 transverse foramen was filled with
      radiopaque material (lead oxide) to simulate the artery and to demarcate the
      danger zone for better visualization on radiography. Measurements and calculation
      of the mean and standard deviation of the height of the area allowing
      instrumentation of the C2 pedicle were done on true lateral view radiograph of
      the C2 pedicle, the sagittal and 30 degrees sagittal views relative to the
      frontal plane passing exactly through the center of the C2 pedicle of CT scans.
      Student t test was applied to calculate the statistical significance of measured
      values. Statistical significance was defined as p<or=.001. RESULTS: On true
      lateral radiographic views of the C2 pedicle, the height of the area allowing
      instrumentation of the pedicle was 7.75+/-0.92 mm (right) and 7.64+/-0.63 (left),
      p>or=.36. Using sagittal CT scan views, the height of pedicles was 7.71+/-0.7 mm
      (right) and 7.58+/-1.01 mm (left), p>or=.23. On 30 degrees sagittal CT scan
      views, the height of pedicles was 7.84+/-1.00 mm (right) and 7.76+/-1.02 mm
      (left), p>or=.27. The p value was >or=.78, >or=.56, and >or=.49 for true lateral
      radiographic view and sagittal CT scan view, true lateral radiographic view and
      30 degrees sagittal CT scan view, and sagittal CT scan view and 30 degrees
      sagittal CT scan views, respectively. On lateral view of cervical spine, the
      decline angle of the transarticular screw was 51.3+/-0.50 degrees (right) and
      50.68+/-0.41 degrees (left), p>or=.17. Mean decline angle was 51+/-0.43 degrees .
      On the anteroposterior (AP) view, radiograph median angle was 6.87+/-0.53 degrees
      (right) and 6.0+/-0.59 degrees (left), p>or=.25. Mean median angle was 6.44+/
      0.62 degrees. CONCLUSIONS: True lateral radiographic views of the pedicles
      provide useful information for defining screw trajectory intraoperatively. Using
      this view along with AP and lateral view of cervical spine and preoperative three
      dimensional CT scan may narrow the margin of error in this delicate area.

PMID- 15996614
TI  - Epidural hematoma secondary to a rupture of a synovial cyst.
AB  - BACKGROUND CONTENT: With modern advances in imaging studies, synovial cysts are
      becoming more evident as a common component of erosive lumbar degenerative disc
      disease causing spinal stenosis and radiculopathy. Whereas hemorrhage can occur
      inside the cyst and is reported, rupture causing epidural hematoma is a rare
      complication and finding of this disorder. PURPOSE: To report a rare clinical
      presentation of a synovial cyst and spinal stenosis, where rupture of the cyst
      leads to an early cauda equina syndrome. STUDY DESIGN: Case report with a review
      of literature. METHODS: Clinical history, physical findings, and magnetic
      resonance imaging studies of a patient with an intraspinal synovial cyst at L4-5
      1 week before a sudden worsening of symptoms are reported. RESULTS: A case report
      is presented of a male with a known synovial cyst at L4-5, presenting initially
      with neurogenic claudication. This patient developed sudden worsening of symptoms
      with bilateral lower extremity pain, weakness, and radiculopathy with difficult
      voiding. The patient had developed an epidural hematoma, secondary to rupture of
      a synovial cyst, documented at surgical decompression. CONCLUSIONS: Although
      synovial cyst associated with erosive facet and erosive degenerative disc disease
      are common, rupture of the cyst is not. A case report of a ruptured synovial cyst
      leading to an early cauda equina syndrome is presented. This case illustrates the
      spectrum of clinical features and presentations possible with spinal stenosis
      complicated by lumbar synovial cyst formation.

PMID- 15996615
TI  - Hemorrhagic lumbar synovial facet cyst secondary to anticoagulation therapy.
AB  - BACKGROUND CONTEXT: Acute onset of radicular symptoms has been reported following
      hemorrhage into lumbar synovial cysts after trauma or in cases of spinal
      instability. No previous cases have been linked to anticoagulation therapy.
      PURPOSE: To present a case of symptomatic hemorrhagic lumbar synovial cyst
      occurring after anticoagulation therapy. STUDY DESIGN: A case report and review
      of the literature. METHODS: A patient presented with low back and radicular pain
      secondary to a large synovial facet cyst. Magnetic resonance imaging revealed a
      large facet cyst compressing the thecal sac and L3 exiting nerve root. RESULTS:
      The synovial cyst was excised during a lumbar decompression and fusion. Gross
      blood was present in the cyst. CONCLUSIONS: This is the first reported case of
      symptomatic hemorrhagic lumbar facet cyst associated with anticoagulation
      therapy.

PMID- 15996616
TI  - Spinal epidural hematoma after a pathologic compression fracture: an unusual
      presentation of multiple myeloma.
AB  - BACKGROUND CONTEXT: Spinal epidural hematoma can result from traumatic and
      atraumatic etiologies. Atraumatic spinal epidural hematomas have been reported as
      an initial presentation of multiple myeloma. There are no other reports
      previously describing spinal epidural hematoma after a pathologic spinal
      fracture. PURPOSE: To present the first reported case of a spinal epidural
      hematoma after a pathologic fracture and a very unusual initial presentation of
      multiple myeloma in a young patient. STUDY DESIGN/SETTING: Case report. METHODS:
      A healthy asymptomatic 37-year-old male was struck in the head with a ball while
      playing soccer. Initial symptoms included severe back pain without neurologic
      symptoms. Complete motor paralysis developed over the next 24 hours in the lower
      extremities with a sensory level of T10. Magnetic resonance imaging evaluation of
      the spine revealed a T6 compression fracture with a dorsal T3 to T10 epidural
      hematoma. The patient underwent surgical T2 to T8 posterior spinal decompression
      with evacuation of the hematoma. Serum and urine electrophoresis and bone marrow
      biopsy were performed. RESULTS: The results of the electrophoresis revealed an
      immunoglobulin A monoclonal spike. The bone marrow biopsy was positive for plasma
      cell myeloma. Recovery of some motor function was noted in both lower extremities
      postoperatively. The patient was subsequently started on steroids and
      chemotherapy for myeloma. The patient has also undergone bone marrow transplant,
      and his myeloma is currently in remission. CONCLUSION: This is the first reported
      case of spinal epidural hematoma after a pathologic spinal fracture. Also, this
      case represents an unusual initial presentation of multiple myeloma in a young
      patient.

PMID- 15996617
TI  - Ganglioneuroma with scoliosis of the thoracic spine: a case report.
AB  - BACKGROUND CONTEXT: Ganglioneuroma is a benign tumor of neural crest origin that
      may provoke a scoliosis as well as neurological symptoms. Treatment includes
      resection with possible spinal fusion for instability and close follow-up for
      many years. PURPOSE: The purpose is to report an invasive ganglioneuroma that was
      successfully treated by resection without spinal fusion. STUDY DESIGN/SETTING:
      Case report. PATIENT SAMPLE: A 15-year-old white female. OUTCOME MEASURES:
      Resolution of the patient's back pain with radiographic and clinical follow-up
      for recurrence of the tumor. METHODS: Not applicable. RESULTS: The patient
      experienced resolution of her back pain without recurrence of the tumor.
      CONCLUSIONS: This is a rare benign tumor that was effectively treated with
      surgical resection and without spinal fusion.

PMID- 15996618
TI  - Neurofibromatosis type I with severe dystrophic kyphoscoliosis and its operative
      management via a simultaneous anterior-posterior approach: a case report and
      review of the literature.
AB  - BACKGROUND CONTEXT: Neurofibromatosis is an autosomal-dominant hereditary
      disorder with two subtypes: NF-1 (type I) and NF-2 (type II). NF-1 is a complex
      disorder with a constellation of manifestations that can also entail skeletal
      abnormalities, including spinal deformity of a noncongenital nature with early
      age onset. The short, sharp, angular curve usually present in the thoracic
      region, as exhibited in NF-1, presents a quandary in its surgical management.
      Various studies have reported on the efficacy of anterior correction as opposed
      to posterior alone, whereas others have advocated a sequential, combined approach
      to diminish the degree of deformity and achieve solid arthrodesis. However,
      despite solid arthrodesis, curve progression may still ensue. Nonetheless, a
      simultaneous anterior-posterior approach to treat such a condition of NF-1 with
      severe dystrophic kyphoscoliosis is a rare occurrence. PURPOSE: To describe the
      presentation and operative management of a patient with NF-1 and severe
      dystrophic kyphoscoliosis. STUDY DESIGN: A case report and review of the
      literature. METHODS: A clinical and radiographic review of a 51-year-old male
      patient who presented with NF-1, a 165-degree thoracic kyphotic deformity,
      associated scoliosis, varied degree of vertebral destruction of T9-T11, and
      paraparesis below T10. RESULTS: Operative intervention of the deformity consisted
      of a simultaneous anterior-posterior approach and entailed posterior cord
      exposure, anterior vertebrectomy of T9-T11, cord decompression, posterior
      osteotomy (posterior elements were auto-fused), anterior distraction and kyphosis
      correction, anterior strut grafting, anterior rod instrumentation, and posterior
      compression instrumentation and fusion from T6-L2. The deformity was reduced,
      sold fusion was noted, and the patient was asymptomatic. CONCLUSIONS: A
      simultaneous anterior-posterior approach for the surgical treatment of severe
      dystrophic kyphoscoliosis in neurofibromatosis type I is an avenue to properly
      visualize the spinal cord, achieve solid arthrodesis, and to minimize as well as
      prevent the progression of deformity.

PMID- 15996619
TI  - Cryptococcal osteomyelitis in a 20-year-old male with sarcoidosis.
AB  - BACKGROUND CONTEXT: We present the case of a 20-year-old male with sarcoidosis
      with cryptococcal infection of the spine. PURPOSE: To present the case and add to
      the existing body of literature on clinical cryptococcal infection. STUDY
      DESIGN/SETTING: An academic tertiary care center. METHODS: Chart review and
      clinical examination.

PMID- 15996620
TI  - Adverse central nervous system sequelae after selective transforaminal block: the
      role of corticosteroids.

PMID- 15996621
TI  - Psychotropic medication in chronic spinal disorders.

PMID- 15996622
TI  - Expression of cardiovascular and behavioural components of conditioned fear to
      context in T4 spinally transected rats.
AB  - A spinal cord transection at the fourth thoracic level (T4) results in
      paraplegia. It also removes supraspinal control of sympathetic outflow to most
      viscera and their blood vessels but spares the heart. We studied the effects of
      such a transection on the expression of the conditioned fear response to context,
      which includes freezing, 22 kHz ultrasonic vocalisations, a marked pressor
      response and a slowly rising tachycardia. Rats implanted with radiotelemetric
      probes were fear conditioned, tested, then transected at T4 and finally re-tested
      4 weeks after transection. Baseline blood pressure in transected animals was the
      same as in intact animals but baseline heart rate was 127 bpm higher. There were
      clear signs of fear in the transected animals: although freezing occurred in the
      upper part of the body only, there was a 3 fold increase in the number of
      ultrasonic vocalisations, most probably due to paralysis of abdominal muscles
      that made expirations shorter and therefore more frequent. The pressor response
      of fear was initially the same as in intact animals but controls revealed that
      this was due to handling during transfer to the aversive context. The rest of the
      pressor response was markedly reduced (70%) confirming that it depends in large
      part on a sympathetically mediated increase in vascular resistance in the lower
      part of the body. The cardiac response was characterized by an initial
      bradycardia followed by a marked tachycardia, which is consistent with a
      baroreceptor-mediated reflex response to the altered pressor changes. Finally,
      none of these changes was observed when the same experiment was repeated in sham
      transected animals. Thus, the pressor response of fear is in large part mediated
      by the thoracic cord below T4 and the baroreflex is not inhibited but maintained
      during conditioned fear.

PMID- 15996623
TI  - Sympathetic activation and tachycardia in lipopolysaccharide treated rats are
      temporally correlated and unrelated to the baroreflex.
AB  - The goal of this study was to investigate the sustained sympatho-excitation which
      occurs in sepsis and which accompanies the fall in blood pressure and to analyze
      its time-correlation with heart rate and the role of the baro-chemoreflexes. Rats
      anesthetized with pentobarbital were treated with lipolysaccharide (LPS) 20
      mg/kg/20 min i.v. and mean blood pressure (MBP), heart rate (HR), rectal
      temperature and renal sympathetic nerve activity (RSNA) were recorded. LPS
      induced a fall in blood pressure, an increase in HR (+20%) and RSNA (+355%); the
      arterial PO2 and PCO2 remained stable and the injection was fatal within 4 h.
      Baroreceptor and chemoreceptor denervation accelerated the fall in MBP but did
      not change the survival time. Under those conditions; RSNA excitation was
      slightly more pronounced. During treatment with gallamine and under artificial
      respiration to avoid possible respiratory changes through the chemoreflex
      pathway, the effects of LPS remained, except for a decrease in arterial PO2.
      Electrolytic lesioning of the nucleus tractus solitarius or blocking the effects
      of baroreflex efferents by either an alpha1 or alpha2-adrenoceptor antagonists
      failed to alter the effects of LPS. After treatment with a beta-adrenoceptor
      antagonist, LPS increased RSNA but not HR and the survival time of the rats
      shortened. LPS administered i.c. (1 mg/kg) induced, with a short latency, effects
      comparable to those produced by i.v. injection. Surprisingly, the time
      correlation between RSNA and HR rhythms persisted when MBP dropped after LPS and
      moreover it reappeared in baroreceptor denervated rats after LPS. Thus under
      these conditions of altered baroreflex pathway and LPS induced sympathetic
      activation, the sympathetic output from the medulla appears to play a role in the
      correlation between heart rate and sympathetic nerve activity. These data
      indicate that the marked RSNA activation and the tachycardia are correlated and
      that the baroreflex and chemoreflex are not inhibited during sepsis but appear to
      be of minor importance in the sympathetic activation and in the blood pressure
      modifications.

PMID- 15996624
TI  - Cervical sympathectomy causes photoreceptor-specific cell death in the rat
      retina.
AB  - Changes in the regulation of the vasculature of the eye may be related to some
      age-related ocular diseases. We have previously shown that loss of sympathetic
      innervation, as can normally occur with age, resulted in substantial vascular
      growth of the choroid. The current study was designed to determine whether
      changes induced by sympathetic denervation causes significant loss of
      photoreceptors and increased glial cell reactivity in the retina. Sympathetic
      denervation was performed followed by immunohistochemistry, TUNEL staining, and
      protein expression analysis to investigate photoreceptor loss. There was a
      significant reduction (30%) in photoreceptor numbers in the sympathectomized eye.
      This loss was due to apoptosis, as there was over a doubling in apoptotic cell
      numbers after sympathectomy. This loss of photoreceptors in the sympathectomized
      eye resulted in a significantly reduced width of the outer nuclear layer of the
      retina when compared to the contralateral eye. Increased glial fibrillary acidic
      protein (GFAP) staining was also noted after sympathectomy in the ganglion cell
      layer with streaking toward the bipolar cell layer. These results suggest that
      loss of sympathetic innervation may cause significant changes to the physiology
      of the choroid.

PMID- 15996625
TI  - Enkephalins and functionally specific vagal preganglionic neurons to the heart:
      ultrastructural studies in the cat.
AB  - In cat, distinct populations of vagal preganglionic and postganglionic neurons
      selectively modulate heart rate, atrioventricular conduction and left ventricular
      contractility, respectively. Vagal preganglionic neurons to the heart originate
      in the ventrolateral part of nucleus ambiguus and project to postganglionic
      neurons in intracardiac ganglia, including the sinoatrial (SA), atrioventricular
      (AV) and cranioventricular (CV) ganglia, which selectively modulate heart rate,
      AV conduction and left ventricular contractility, respectively. These ganglia
      receive projections from separate populations of vagal preganglionic neurons. The
      neurochemical anatomy and synaptic interactions of afferent neurons which mediate
      central control of these preganglionic neurons is incompletely understood.
      Enkephalins cause bradycardia when microinjected into nucleus ambiguus. It is not
      known if this effect is mediated by direct synapses of enkephalinergic terminals
      upon vagal preganglionic neurons to the heart. The effects of opioids in nucleus
      ambiguus upon AV conduction and cardiac contractility have also not been studied.
      We have tested the hypothesis that enkephalinergic nerve terminals synapse upon
      vagal preganglionic neurons projecting to the SA, AV and CV ganglia. Electron
      microscopy was used combining retrograde labeling from the SA, AV or CV ganglion
      with immunocytochemistry for enkephalins in ventrolateral nucleus ambiguus. Eight
      percent of axodendritic synapses upon negative chronotropic, and 12% of
      axodendritic synapses upon negative dromotropic vagal preganglionic neurons were
      enkephalinergic. Enkephalinergic axodendritic synapses were also present upon
      negative inotropic vagal preganglionic neurons. Thus enkephalinergic terminals in
      ventrolateral nucleus ambiguus can modulate not only heart rate but also
      atrioventricular conduction and left ventricular contractility by directly
      synapsing upon cardioinhibitory vagal preganglionic neurons.

PMID- 15996626
TI  - Cloning and characterization of the Pichia pastoris MET2 gene as a selectable
      marker.
AB  - We describe the isolation and characterization of a new biosynthetic gene, MET2,
      from the methylotrophic yeast Pichia pastoris. The predicted product of PpMET2 is
      significantly similar to its Saccharomyces cerevisiae counterpart, ScMET2, which
      encodes homoserine-O-transacetylase. The ScMET2 was able to complement the P.
      pastoris met2 strain; however, the converse was not true. Expression vectors
      based on PpMET2 for the intracellular and secreted production of foreign proteins
      and corresponding auxotrophic strains were constructed and tested for use in
      heterologous expression. The expression vectors and corresponding strains provide
      greater flexibility when using P. pastoris for recombinant protein expression.

PMID- 15996627
TI  - A set of epitope-tagging integration vectors for functional analysis in
      Saccharomyces cerevisiae.
AB  - Functional analysis of genes from Saccharomyces cerevisiae has been the major
      goal after determination of genome sequences. Even though several tools for
      molecular-genetic analyses have been developed, only a limited number of reliable
      genetic tools are available to support functional assay at protein level. Epitope
      tagging is a powerful tool for detecting, purifying, and functional studying of
      proteins. But systematic tagging systems developed with integration vectors are
      not available. Here, we have constructed a set of integration vectors allowing a
      translational fusion of interested proteins to the four different epitope tags
      (HA, Myc, Flag, and GFP). To confirm function and expression of C-terminal-tagged
      proteins, we used Cdc11, a component of the septin filament that encircles the
      mother bud neck and consists of five major proteins: Cdc3, Cdc10, Cdc11, Cdc12,
      and Sep7. The tagged version of Cdc11 expressed under its endogenous promoter was
      found to be physiologically functional, as evidenced by localization at the neck
      and suppression of the growth defect associated with the temperature-sensitive
      mutation of cdc11-6. The expressed proteins were efficiently detected with
      antibodies against Cdc11 or the epitopes. When immunoprecipitated with anti-Myc
      antibody, each septin protein tagged with Myc was effectively copurified with
      other septin components, indicating formation of a stable septin complex. Because
      the modules of the tags were located under the same array of eighteen restriction
      sites on integration vectors containing four different markers (HIS3, TRP1, LEU2,
      or URA3), this tagging system provides efficient multiple tagging and stable
      expression of a gene of interest.

PMID- 15996629
TI  - Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability
      of finding relevant pathologies in an open access service?
AB  - BACKGROUND: This prospective study examined the appropriate use of colonoscopy in
      an open-access system with the American Society for Gastrointestinal Endoscopy
      guidelines and determined whether the American Society for Gastrointestinal
      Endoscopy guidelines were associated with relevant endoscopic findings. METHODS:
      In a cohort of 2221 consecutive patients referred for colonoscopy, the proportion
      of patients who underwent colonoscopy for appropriate indications was
      prospectively assessed. The relationship between appropriateness and the presence
      of clinically relevant endoscopic diagnoses was assessed by calculating (1) the
      positive and negative likelihood ratio of the indications; and (2) the change in
      the probability of relevant endoscopic diagnoses in the presence of the American
      Society for Gastrointestinal Endoscopy criteria. RESULTS: The rate for 'generally
      not indicated' colonoscopies was 37%. Relevant endoscopic diagnoses were present
      in 28.5% of cases with American Society for Gastrointestinal Endoscopy
      indications versus 20.1% of patients without appropriate indications. However,
      the risk of finding relevant diagnoses was significantly increased by American
      Society for Gastrointestinal Endoscopy criteria application (odds ratio (OR)
      1.58; 99% CI 1.20-2.07; p<0.01). Furthermore, in both endoscopic situations
      (appropriate and not appropriate), the likelihood ratio, positive and negative,
      varied very little, suggesting a low predictivity for serious pathologies by the
      appropriate procedure. CONCLUSIONS: The use of an appropriateness evaluation
      system makes it possible to increase the probability of finding relevant
      endoscopic diseases. However, the exclusive use of such a system for selecting
      patients to undergo colonoscopy involves a relatively high risk of colorectal
      neoplasms going undetected.

PMID- 15996628
TI  - One-week once-daily triple therapy with esomeprazole, levofloxacin and
      azithromycin compared to a standard therapy for Helicobacter pylori eradication.
AB  - BACKGROUND: Primary antibiotic-resistance and poor compliance are the main causes
      of Helicobacter pylori eradication failure of standard regimens. AIM: To
      investigate eradication rate, patient compliance and tolerability of a 1-week
      once-daily levofloxacin plus azithromycin triple therapy versus the standard
      twice-daily triple therapy. PATIENTS AND METHODS: A total of 164 H. pylori
      positive patients were randomised to either esomeprazole 20mg, levofloxacin 500
      mg and azithromycin 500 mg once-daily (ELAz) or esomeprazole 20mg, clarithromycin
      500 mg and amoxycillin 1g twice-daily (ECA) for 1 week. H. pylori infection was
      defined at entry by histology and urea breath test; cure of infection was
      determined both by negative urea breath test and H. pylori stool antigens.
      RESULTS: H. pylori eradication rates of ELAz and ECA were similar at intention-to
      treat (both 65%) and per-protocol analyses (70% versus 76%, respectively).
      Incidence of poor compliance was lower, although not significantly, in patients
      randomised to ELAz than to ECA (4% versus 10%); tolerability was significantly
      higher for ELAz than for ECA (88% versus 70%; P=0.01). CONCLUSIONS: Once-daily
      levofloxacin plus azithromycin-based triple therapy achieves an H. pylori
      eradication rate comparable to that of standard twice-daily triple therapy, but
      is associated with higher patient compliance and might even be better tolerated.

PMID- 15996630
TI  - The changing pattern of hepatitis B virus infection over the past three decades
      in Italy.
AB  - By the end of 1970s, Italy was a country at medium endemic level of hepatitis B
      virus infection, with wide geographical differences; intrafamily transmission was
      the major mode by which infection spread; hepatitis B e antigen positivity and
      hepatitis Delta positivity were frequently detected in hepatitis B surface
      antigen chronic carriers; a high proportion of subjects with chronic liver
      disease resulted as hepatitis B surface antigen positive. Three decades apart,
      the picture was completely changed, as documented by several surveys. Nowadays,
      Italy is a country at very low endemic level of hepatitis B, without geographical
      differences; the infection is mostly sexually transmitted; hepatitis B e antigen
      positivity and hepatitis Delta positivity are rarely detected in hepatitis B
      surfaces antigen chronic carriers; a low proportion of subjects with chronic
      liver disease result hepatitis B surface antigen positive. These important
      changes may be due to both non-specific (i.e. improvement in socio-demographic
      features) and specific (i.e. a comprehensive vaccination program against
      hepatitis B) preventive measures.

PMID- 15996631
TI  - Slow evolution of liver metastasis from colon cancer.

PMID- 15996632
TI  - Lubrication during colonoscopy: a forgotten factor.

PMID- 15996634
TI  - Epidemiology and surveillance: changing the global picture of malaria--myth or
      reality?
AB  - The burden of malaria remains unacceptably high, and the greatest burden is borne
      by the African continent. There is now wide agreement on the control strategies
      and tools, and a considerable increase in global resources invested in malaria
      control efforts. However, challenges remain, especially with achieving the
      necessary population coverage with these interventions in order to change the
      epidemiology of the disease. Existing tools may not be optimal, and are liable to
      fail with time, just as previous ones did. Current global antimalarial efforts
      need to be underpinned by a strong research and development agenda. If all these
      factors are taken into consideration, reducing the burden of malaria would seem
      more like a reality than a myth in the foreseeable future.

PMID- 15996635
TI  - [Septic risk and prostheses: new complications and a new semeiology].

PMID- 15996636
TI  - Regulation of erythrocyte Na-K-2Cl cotransport by threonine phosphorylation.
AB  - A method is described to measure threonine phosphorylation of the Na-K-2Cl
      cotransporter in ferret erythrocytes using readily available antibodies. We show
      that most, if not all, cotransporter in these cells is NKCC1, and this was
      immunoprecipitated with T4. Cotransport rate, measured as 86Rb influx, correlates
      well with threonine phosphorylation of T4-immunoprecipitated protein. The
      cotransporter effects large fluxes and is significantly phosphorylated in cells
      under control conditions. Transport and phosphorylation increase 2.5- to 3-fold
      when cells are treated with calyculin A or Na+ arsenite. Both fall to 60% control
      when cell [Mg2+] is reduced below micromolar or when cells are treated with the
      kinase inhibitors, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine or staurosporine. Importantly, these latter interventions do not
      abolish either phosphorylation or transport suggesting that a phosphorylated form
      of the cotransporter is responsible for residual fluxes. Our experiments suggest
      protein phosphatase 1 (PrP-1) is extremely active in these cells and
      dephosphorylates key regulatory threonine residues on the cotransporter.
      Examination of the effects of kinase inhibition after cells have been treated
      with high concentrations of calyculin indicates that residual PrP-1 activity is
      capable of rapidly dephosphorylating the cotransporter. Experiments on
      cotransporter precipitation with microcystin sepharose suggest that PrP-1 binds
      to a phosphorylated form of the cotransporter.

PMID- 15996637
TI  - The Rab-interacting lysosomal protein, a Rab7 and Rab34 effector, is capable of
      self-interaction.
AB  - Rab-interacting lysosomal protein (RILP) has been identified as an interacting
      partner of the small GTPases Rab7 and Rab34. Active Rab7 recruits RILP on the
      late endosomal/lysosomal membrane and RILP then functions as a Rab7 effector
      controlling transport to degradative compartments. Indeed, RILP induces
      recruitment of dynein-dynactin motor complexes to Rab7-containing late endosomes
      and lysosomes. Recently, Rab7 and RILP have been found to be key proteins also
      for the biogenesis of phagolysosomes. Therefore, RILP represents probably an
      important factor for all endocytic routes to lysosomes. In this study, we show,
      using the yeast two-hybrid system, that RILP is able to interact with itself. The
      data obtained with the two-hybrid system were confirmed using co
      immunoprecipitation in HeLa cells. The data together indicate that RILP, as
      already demonstrated for several other Rab effector proteins, is capable of self
      association, thus probably forming a homo-dimer.

PMID- 15996638
TI  - Effect of statins on the proteasomal activity in mammalian endothelial and
      vascular smooth muscle cells.
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins,
      effectively prevent cardiovascular events. In addition to their lipid lowering
      properties, a variety of pleiotropic effects on cardiovascular cells were
      demonstrated in vitro and in vivo. It has been hypothized that statins deploy a
      part of their effects by targeting the proteasome. Statin-induced effects
      remarkably overlap with effects obtained by inhibition of the proteasome in
      endothelial and vascular smooth muscle cells (e.g., endothelial nitric oxide
      synthase (eNOS)-upregulation, attenuation of nuclear factor kappa B (NF-kappaB)
      activation, inhibition of proliferation). We therefore examined, whether statins
      modulate the proteasomal activity of vascular cells. We studied the effect of
      simvastatin, atorvastatin, and pravastatin as well as of the proteasome inhibitor
      clasto-lactacystin on morphology, proliferation, viability, and proteasomal
      activity in two mammalian endothelial cell lines (CPAE and Ea.hy962), and in
      primary vascular smooth muscle cells (VSMCs). Both statins and lactacystin
      induced comparable morphological changes and attenuated proliferation of calf
      pulmonary artery cell line (CPAE). Whereas the statin-induced effects were
      reversed by mevalonic acid, however, the lactacystin-induced alterations were not
      influenced by mevalonic acid. As expected, lactacystin caused a significant loss
      of proteasomal activity measured in the extract of treated CPAE cells, whereas
      the extracts of statin-treated CPAEs exhibited unchanged activities. This result
      was also confirmed in Ea.hy926 cells and in primary rat VSMCs. We show here, that
      even high doses of statins do not modulate the activities of purified human 20S
      proteasomes. We conclude that the similar biological effects of statins and
      proteasome inhibitors in vascular cells are not due to a common inhibitory
      mechanism of action on the proteasome.

PMID- 15996639
TI  - Influence of the dopamine D2 receptor knockout on pain-related behavior in the
      mouse.
AB  - We studied the role of the dopamine D2 receptor in physiological regulation of
      pain-related behavior. The experiments were performed in dopamine D2 receptor
      knockout mice and in their wild-type controls. Baseline sensitivity to thermal
      nociception was determined by measuring the response latency in the hot plate at
      three different stimulus temperatures and by determining the radiant-heat-induced
      paw withdrawal. Mechanical sensitivity was assessed by determining paw withdrawal
      responses to stimulation with a calibrated series of monofilaments. Intracolonic
      capsaicin was used to produce sustained pain-related behavior and referred
      hypersensitivity to mechanical stimulation. The hot plate response latencies were
      not significantly different between the dopamine D2 receptor knockout and wild
      type animals, although the stimulus temperature-dependent decrease in the
      response latency was steeper in the wild-type group. The radiant-heat-induced paw
      withdrawal latency was slightly longer in the knockout animals. The number of
      capsaicin-induced behavioral responses or the latency to the occurrence of the
      first capsaicin-induced response was not different between the experimental
      groups. Dopamine D2 receptor knockout animals were more sensitive to mechanical
      stimulation of the hindpaws than wild-type animals both in the baseline condition
      and following development of capsaicin-induced referred hypersensitivity in the
      hindpaws. The results indicate that dopamine D2 receptors influence baseline
      nociception in the mouse, although this effect is weak and submodality selective.
      Additionally, dopamine D2 receptors may contribute to attenuation of referred
      hypersensitivity caused by sustained nociception.

PMID- 15996640
TI  - Neural cograft stimulates the survival and differentiation of embryonic stem
      cells in the adult mammalian auditory system.
AB  - Mouse embryonic stem (ES) cells were transplanted into the cochlea of adult
      guinea pigs in order to explore their survival, differentiation, and possible
      integration with the host tissue. With the purpose of investigating the possible
      effect of manipulating the local embryonic microenvironment, ES cells were
      transplanted into the cochlea with or without an embryonic neuronal cograft
      consisting of dorsal root ganglion (DRG) tissue. To detect the survival and
      differentiation of ES cells, cells expressing green fluorescent protein (GFP)
      were used in combination with immunohistochemical detection of a neuronal marker,
      neural class III beta-tubulin (TUJ1 antibody). At 4 weeks following
      transplantation implanted ES cells were found close both to the sensory
      epithelium, and the spiral ganglion neurons (SGNs) with their peripheral
      dendritic processes projecting to the organ of Corti. There was a significant
      difference in the number of surviving TUJ1 (+) ES cells between the DRG cograft
      group and the non-cograft group (P < 0.01, ANOVA). Neurite-like projections were
      also identified between TUJ1-positive ES cells and the peripheral dendritic
      processes from SGNs. The results suggest that an embryonic neuronal
      microenvironment may be one of the key factors in the survival and
      differentiation of ES cells in the adult auditory system.

PMID- 15996641
TI  - The engraftment of transplanted bone marrow-derived cells into the olfactory
      epithelium.
AB  - To investigate whether bone marrow cells migrate and are engrafted into the
      olfactory epithelium and differentiate into olfactory neurons, bone marrow cells
      of green fluorescence protein (GFP) mice were transplanted into lethally
      irradiated recipient mice. Immunohistochemical staining was performed to evaluate
      the engraftment of donor bone marrow cells into the olfactory epithelium.
      Immunostaining for GFP was found initially in the olfactory epithelium 2 weeks
      after bone marrow reconstruction. The percentage of GFP positive cells increased
      up to 12 months after bone marrow reconstruction. Double staining for GFP and
      olfactory marker protein showed that a population of the GFP-positive cells had
      characteristics of olfactory neurons. These results demonstrate that bone marrow
      cells can be engrafted in the olfactory epithelium and then differentiate into
      olfactory neuron cells.

PMID- 15996642
TI  - Fos-like immunoreactivity in the brain associated with freezing or escape induced
      by inhibition of either glutamic acid decarboxylase or GABAA receptors in the
      dorsal periaqueductal gray.
AB  - GABAergic neurons exert tonic control over the neural substrates of aversion in
      the dorsal periaqueductal gray (dPAG). It has been shown that electrical
      stimulation of this region 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 investigate this issue further, reduction of
      GABA transmission was performed with local injections of either the GABA-A
      receptor antagonist bicuculline or the glutamic acid decarboxylase (GAD)
      inhibitor semicarbazide into the dorsolateral periaqueductal gray (dlPAG). Local
      infusions of semicarbazide (5.0 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 laterodorsal nucleus of the thalamus
      (LD) and ventrolateral periaqueductal gray (vlPAG), while bicuculline-induced
      escape was related to widespread increase in Fos labeling, notably in the columns
      of the periaqueductal gray, hypothalamus nuclei, the central amygdaloid nucleus
      (Ce), the 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 dlPAG are neurally segregated: freezing activates only
      structures that are mainly involved in sensory processing, and bicuculline
      induced escape activates structures involved in both sensory processing and motor
      output of defensive behavior. Therefore, the freezing elicited by activation of
      dlPAG appears to be related to the acquisition of aversive information, whereas
      most brain structures involved in the defense reaction are recruited during
      escape.

PMID- 15996643
TI  - Effects of neurotransmitter agonists on electrocortical activity in the rat
      kainate model of temporal lobe epilepsy and the modulatory action of basic
      fibroblast growth factor.
AB  - We used systemic kainic acid (KA) injection to investigate how the development of
      temporal lobe epilepsy and the associated network reorganization affect the
      electrocorticogram (ECoG) responses to various neurotransmitter agonists.
      Unrestrained rats chronically implanted with electrodes over somatosensory cortex
      and dorsal hippocampus and a cannula into the right lateral ventricle were used
      to investigate the ECoG frequency responses of intracerebroventricularly applied
      agonists (NMDA, clonidine, muscimol, and baclofen) at several types of receptors
      [NMDA, alpha2-adrenergic (NE), GABAA, and GABAB, respectively] in KA-treated
      versus naive animals. The ECoG was analyzed 2, 5, and 9 weeks after
      intraperitoneal injection of KA alone or in combination with basic fibroblast
      growth factor (bFGF, intracerebroventricularly). Within the first 5 weeks of KA
      injection, the ECoG power shifted towards the lower-frequency range.
      Concurrently, the electrographic responses to NMDA and clonidine were
      potentiated, whereas the ECoG effects mediated by GABAA and GABAB receptors
      remained largely unaffected. In control rats, bFGF strongly enhanced the
      electrographic NMDA responses. In sharp contrast, bFGF potently mitigated the
      abnormally increased NMDA sensitivity of epileptic rats, if applied 4 weeks post
      KA injection. These data suggest that upregulation and downregulation of the NMDA
      receptor-mediated effects on cortical activity might be a prominent feature of
      bFGF signaling in the intact and the damaged brain, respectively.

PMID- 15996644
TI  - Synthesis of sterically crowded derivatives of anomeric pairs of D-glucose
      disaccharides.
AB  - Derivatization of carbohydrates is of considerable interest since the derivatives
      can be used for structural studies in the field of mass spectrometry. We report
      here the synthesis of a series of sterically crowded derivatives of various
      linkage and stereo-isomeric glucose-glucose disaccharides with the impetus being
      to understand the effect of these derivatized groups on fragmentation of the
      glycosidic bond and the development of methodology for discernment of the
      anomeric configuration. The synthesis of per-alkylated (methyl, ethyl, propyl,
      butyl, and pentyl), per-esterified (acetyl, pivaloyl, mesitoyl), and per
      silylated (tert-butyl-dimethyl silyl) glucose--glucose disaccharide derivatives
      has been reported.

PMID- 15996645
TI  - Enhanced glucose absorption in the rat small intestine following repeated doses
      of 5-fluorouracil.
AB  - Many studies demonstrated that 5-fluorouracil (5-FU) treatment of rodents caused
      the damage of small intestine, resulting in the malabsorption, while we recently
      found that repeated administration of 5-FU to rats increased Na(+)-dependent
      glucose absorption in the small intestine. This study investigated the cause of
      enhanced glucose absorption. 3-O-methyl-d-glucose (3-OMG) absorption was examined
      using the everted intestine technique. d-Glucose uptake, phlorizin binding,
      Western blot analysis and membrane fluidity were examined using small intestinal
      brush-border membrane vesicles (BBMV). Repeated oral administration of 5-FU to
      rats increased Na(+)-dependent 3-OMG absorption in the small intestine, while
      alkaline phosphatase activity in the small intestine decreased. Na(+)/K(+)-ATPase
      activity of 5-FU-treated rats was about three-fold higher than that of control
      rats. Although the amount of Na(+)-dependent glucose co-transporter (SGLT1) in 5
      FU-treated rats decreased, the overshoot magnitude of d-glucose uptake in BBMV
      was not altered. Maximum binding of phlorizin in 5-FU-treated rats was 1.5-fold
      larger than that of control rats, but not altered the maximal rate of d-glucose
      absorption, Michaelis constant of d-glucose and dissociation constant of
      phlorizin. The membrane fluidity of 5-FU-treated rats increased. The enhanced d
      glucose absorption in 5-FU-treated rats seems to occur secondarily due to the
      activation of Na(+)/K(+)-ATPase activity in basolateral membranes (BLM). Because
      the amounts of SGLT1 in 5-FU-treated rats decreased, the increase of turnover
      rate of SGLT1 and/or an expression of unknown Na(+)-dependent glucose co
      transporter with high affinity for d-glucose and phlorizin sensitivity would
      contribute to the enhancement of d-glucose transport in 5-FU-treated rats.

PMID- 15996646
TI  - Rapid and highly sensitive determination of trace proteins using dibromomethyl
      carboxyazo-Pb(II) complex as a spectroscopic reagent.
AB  - BACKGROUND: The concentration of protein in body fluids is an important measure
      in disease diagnosis and in analytical biochemistry. Searching for a sensitive
      and rapid method for proteins is an ongoing subject of investigation. We describe
      the reaction of dibromomethyl carboxyazo-Pb(II) with proteins found in urine.
      METHODS: In a buffer containing of HCl and KCl at pH 1.80, dibromomethyl
      carboxyazo-Pb(II) complex combined with proteins to form a colored compound. The
      reaction was completed in 2 min and remained stable for 80 min. Under optimum
      conditions, the product of reaction between protein and dibromomethyl carboxyazo
      Pb(II) absorbed at 530 nm and was linear in the range of 0-50 microg/ml of BSA.
      Moreover, the maximum binding number was defined to express the binding ability
      of dibromomethyl carboxyazo-Pb(II) to protein under a given set of conditions.
      RESULTS: The method was applied to the determination of urine proteins. The
      recovery of protein from human urine was 97.6-103% and the precision was <4.8%.
      Results compared favorably to the Biuret and Bradford protein methods on 50 urine
      samples. CONCLUSIONS: This method had high sensitivity and specificity and may be
      applicable to clinical analysis.

PMID- 15996647
TI  - Messenger RNA expression of glomerular podocyte markers in the urinary sediment
      of acquired proteinuric diseases.
AB  - BACKGROUND: Podocyte slit diaphragm plays an important role in the control of
      glomerular permeability. We hypothesize that studying the gene expression profile
      of podocyte in urinary sediment may provide diagnostic and prognostic information
      on acquired proteinuric diseases. METHODS: We studied 28 patients who required
      kidney biopsy for acquired proteinuric diseases (diabetic glomerulosclerosis, 9
      cases; IgA nephropathy, 10 cases; minimal change disease, 5 cases; membranous
      nephropathy, 5 cases). We also studied 10 cases of diabetic microalbuminuria and
      9 healthy controls. The mRNA expressions of nephrin (NephRNA), podocin (PodRNA)
      and synaptopodin (SynRNA) in urinary sediment were measured by real time
      quantitative PCR. After recruitment, all patients were followed for at least 12
      months. RESULTS: There were significant differences in the NephRNA and PodRNA in
      the urinary sediment between diagnosis groups (p<0.005). On the other hand,
      SynRNA was only marginally significant between diagnosis groups (p<0.05).
      Although statistically significant, the degree of proteinuria had only modest
      correlations with the urinary expression of nephrin. After a median follow up for
      23 months, there was a significant correlation between the rate of decline in
      renal function and NephRNA (r=0.559, p=0.001) and PodRNA (r=0.530, p=0.002), but
      not SynRNA (r=0.054, p=NS). The correlation remained statistically significant
      after multivariate analysis to adjust for the degree of proteinuria and initial
      renal function. CONCLUSIONS: Urinary mRNA expression of podocyte markers, such as
      nephrin and podocin, are significantly different between proteinuric disease
      categories. Further, NephRNA and PodRNA correlated with the rate of decline in
      renal function. Our results suggest that urinary podocyte gene expression may be
      a useful non-invasive tool which provides additional information for the
      management of proteinuric diseases.

PMID- 15996648
TI  - Increased creatine kinase BB activity and CKB mRNA expression in patients with
      hematologic disorders: relation to methylation status of the CKB promoter.
AB  - BACKGROUND: We encountered 2 patients with increased activities of the creatine
      kinase (CK)-BB isoenzyme in their sera. Here we examined the relation among CK-BB
      activity, expression of CKB mRNA in peripheral blood, and hypermethylation of the
      CKB. METHODS: The 2 patients and other 26 patients with hematologic malignancies,
      and some cancer cell lines were subjected to measurement of serum CK activity, CK
      isoenzyme analysis, CKB mRNA expression analysis by RT-PCR, and methylation
      analysis of the CKB promoter region. RESULTS: CK-BB activity and proportion of
      leukemia blasts were correlated in the 2 patients. CKB mRNA was increased in
      peripheral blood during an increase in leukemia blast numbers. In contrast, none
      of the other 26 patients showed CK-BB activity or expression of CKB mRNA. In all
      of the patients with hematologic disorders, the analyzed region of CKB promoter
      was mostly unmethylated. However, some of cancer cell lines showed the methylated
      pattern. CKB mRNA was expressed at higher levels in cells with an unmethylated
      CKB promoter than in cells with a methylated promoter. CONCLUSIONS: Expression of
      CKB mRNA and CK-B sometimes occurred in blastic transformation of the
      hematopoietic system. A relation between CKB mRNA expression and methylation of
      the CKB promoter was suggested.

PMID- 15996649
TI  - Performance validation of a third-generation allergen-specific IgE assay in the
      clinical laboratory: interlaboratory and intermethod comparison.
AB  - BACKGROUND: Allergen-specific IgE (sIgE) measurements are used to help identify
      causative allergenic agents and to determine the degree of sensitization to
      facilitate treatment decisions. We examined the performance of a new third
      generation chemiluminescent enzyme immunoassay for allergen-specific IgE (sIgE)
      on the continuous random access Immulite 2000 system. METHODS: Detection limit
      and dilutional linearity were determined. Within-run and total precision were
      assessed according to the NCCLS EP5 guideline. Interlaboratory comparison of the
      new Immulite 2000 third-generation allergen-specific IgE assay was performed, as
      well as intermethod comparison against the Pharmacia FEIA, a second-generation
      assay. RESULTS: The detection limit was <0.1 kU/l. Dilutional linearity held from
      100 down to 0.2 kU/l. Regression analysis of the interlaboratory comparison
      results yielded: Immulite 2000(Laboratory 1)=1.07 Immulite 2000(Laboratory
      2)+0.18 kU/l; r=0.98, n=3588 results. Intermethod comparison showed the
      following: Immulite 2000=0.83 (Pharmacia FEIA)+0.42 kU/l; r=0.79, n=512 results.
      Bland-Altman analysis of the interlaboratory and intermethod comparisons
      indicated no systematic bias. CONCLUSIONS: We confirmed the reported performance
      characteristics of the third-generation sIgE assay and found reasonably good
      interlaboratory and intermethod agreement. The extended range capability of the
      third-generation assay provides a new tool for investigating cutoffs and trends
      in childhood allergy disease progression at concentrations <0.35 kU/l.

PMID- 15996650
TI  - Complement activation and diabetic vascular complications.
AB  - Diabetes mellitus is a major and increasing health problem worldwide. One of the
      most serious consequences of diabetes is the development of diabetic angiopathy,
      which includes cardiovascular disease, neuropathy, retinopathy and nephropathy.
      Diabetic nephropathy alone affects 15-25% of patients with type 1 diabetes and 30
      40% of patients with type 2 diabetes and is the single-most important cause of
      end-stage renal failure in the Western World. Existing research has demonstrated
      the involvement of glycation factors, growth factors/cytokines, hemodynamic
      factors and intracellular changes in the pathogenesis of diabetic kidney disease.
      An emerging amount of recent data suggests that the complement system, especially
      the MBL pathway, plays an important role in the pathogenesis of diabetic vascular
      complications. Although the numerous therapeutic interventions available today
      may delay the development and progression of diabetes vascular complications,
      there is an ongoing need for new therapeutic strategies. In this article the
      evidence for a connection between the complement system and vascular dysfunction
      will be reviewed, with a special focus on the relation to diabetic kidney
      disease. Several ways of specifically manipulating the complement system already
      exist. However, whether or not these drugs provide new targets for intervention
      on diabetic vascular complications is still unknown.

PMID- 15996651
TI  - Analbuminemia in a Swiss family is caused by a C --> T transition at nucleotide
      4446 of the albumin gene.
AB  - OBJECTIVE: To define the molecular defect that causes analbuminemia in an
      apparently healthy boy, son of non-consanguineous Swiss parents. DESIGN AND
      METHODS: Total DNA, extracted from peripheral blood samples from the proband and
      from both parents, was PCR-amplified using oligonucleotide primers designed to
      amplify the 14 exons of the human albumin gene and the flanking intron regions.
      The products were screened for mutations by single-strand conformation
      polymorphism (SSCP) and heteroduplex analyses (HA) either directly or after
      digestion with restriction enzymes. The combination of these methods identified
      the abnormal fragment, which was then sequenced. RESULTS: DNA sequence analysis
      identified in the homozygous proband a C --> T transition at nucleotide 4446. The
      mutation changes the codon CGA for Arg 114 to a stop codon TGA, resulting in
      premature termination and is therefore responsible for the analbuminemic trait.
      The same mutation has been previously reported to cause analbuminemia in an
      American female. The putative protein product would have a length of 113
      residues. The parents were found to be heterozygous for the mutation.
      CONCLUSIONS: Gel-based mutation detection and DNA sequencing confirmed the
      diagnosis of congenital analbuminemia in the proband. Our results show that the
      combination of SSCP and HA represents a powerful tool to study the molecular
      defects causing analbuminemia in humans.

PMID- 15996652
TI  - Loss of Gbx2 results in neural crest cell patterning and pharyngeal arch artery
      defects in the mouse embryo.
AB  - Several syndromes characterized by defects in cardiovascular and craniofacial
      development are associated with a hemizygous deletion of chromosome 22q11 in
      humans and involve defects in pharyngeal arch and neural crest cell development.
      Recent efforts have focused on identifying 22q11 deletion syndrome modifying
      loci. In this study, we show that mouse embryos deficient for Gbx2 display
      aberrant neural crest cell patterning and defects in pharyngeal arch-derived
      structures. Gbx2(-/-) embryos exhibit cardiovascular defects associated with
      aberrant development of the fourth pharyngeal arch arteries including interrupted
      aortic arch type B, right aortic arch, and retroesophageal right subclavian
      artery. Other developmental abnormalities include overriding aorta, ventricular
      septal defects, cranial nerve, and craniofacial skeletal patterning defects.
      Recently, Fgf8 has been proposed as a candidate modifier for 22q11 deletion
      syndromes. Here, we demonstrate that Fgf8 and Gbx2 expression overlaps in regions
      of the developing pharyngeal arches and that they interact genetically during
      pharyngeal arch and cardiovascular development.

PMID- 15996653
TI  - Null mutants of Drosophila B-type lamin Dm(0) show aberrant tissue
      differentiation rather than obvious nuclear shape distortion or specific defects
      during cell proliferation.
AB  - To elucidate the function of metazoan B-type lamins during development, new null
      mutations of the Drosophila B-type lamin gene, lamDm(0), were analyzed in
      parallel with the misg(sz18) mutation, a lamDm(0) allele reported previously.
      Although in all these mutants, lamin Dm(0) protein was undetectable in
      neuroblasts and imaginal disc cells from the second instar larval stage onward,
      cells continued to proliferate. In contrast to the embryonic lethality of another
      Drosophila lamDm(0) allele, lam(PM15), reported previously, lethality did not
      occur until late pupal stages. Chromosomal structure and the overall nuclear
      shape remained normal even at these late pupal stages, although obviously
      abnormal nuclear pore complex distribution was observed concomitant with the loss
      of lamin Dm(0) protein. Compensating expression of lamin C was not induced in the
      absence of lamin Dm(0). Thus, no lamin-containing nuclear structures were found
      in proliferating larval neuroblasts. We did find that developmental abnormalities
      appeared in specific organs during the late pupal stage, preceding lethality.
      Surprisingly, coordinated size increase (hypertrophy) of the ventriculus was
      observed accompanied by cell division and muscle layer formation. Hypertrophy of
      the ventriculus correlated with a decrease in ecdysteroid hormone receptor B1
      (EcRB1) protein, and furthermore could be suppressed by a heat-inducible EcRB1
      transgene. In contrast, both gonadal and CNS tissues exhibited underdevelopment.

PMID- 15996654
TI  - Pregnenolone sulfate acts through a G-protein-coupled sigma1-like receptor to
      enhance short term facilitation in adult hippocampal neurons.
AB  - Neurosteroids have been linked to cognitive performance, and their levels are
      altered in neuropsychiatric diseases. These neuromodulators are produced in the
      brain where they have important effects on synaptic transmission at postsynaptic
      gamma-amino-butyric acid receptors and N-methyl-D-aspartate receptors and at
      presynaptic sites. We previously found, in cultured neonatal hippocampal neurons,
      that the neurosteroid, pregnenolone sulfate, acts presynaptically through a
      sigma1-like receptor to modulate basal glutamate release. The present study was
      designed to test whether pregnenolone sulfate acts through a similar presynaptic
      receptor in adult hippocampal neurons. The sigma1-receptor agonist, 2-(4
      morpholino)ethyl-1-phenylcyclohexane-1-carboxylate, enhanced paired-pulse
      facilitation (PPF) by a similar extent to that which we had previously reported
      for pregnenolone sulfate. The sigma1-receptor antagonists, 1-(4-Iodophenyl)-3-(2
      adamantyl)guanidine and 1[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine,
      blocked the pregnenolone sulfate enhancement of PPF as did pretreatment of slices
      in pertussis toxin. We conclude that pregnenolone sulfate acts through a Gi/o
      coupled sigma1-like receptor to enhance short-term presynaptic facilitation onto
      adult hippocampal CA1 neurons.

PMID- 15996655
TI  - Capsazepine, a vanilloid receptor antagonist, inhibits allergen-induced tracheal
      contraction.
AB  - To investigate the possible role of the vanilloid receptor-1 (TRPV1) in allergic
      airway responses, the effect of the specific TRPV1 receptor antagonist
      capsazepine was examined. Capsazepine significantly decreased the ovalbumin
      induced contraction of isolated tracheal rings from ovalbumin-sensitized guinea
      pigs. This is the first report directly showing the involvement of the TRPV1 in
      experimental allergic airway responses.

PMID- 15996656
TI  - VEGF189 stimulates endothelial cells proliferation and migration in vitro and up
      regulates the expression of Flk-1/KDR mRNA.
AB  - The vascular endothelial growth factor (VEGF) is a critical factor for
      development of the vascular system in physiological and pathological
      angiogenesis. This growth factor exists under at least three isoforms,
      VEGF120/121, VEGF164/165 and VEGF188/189 which are generated by alternative
      splicing. VEGF isoforms have different affinities for heparan sulphate as well as
      for VEGF receptors, and may play distinct roles in vascular development. The role
      of VEGF189 as an endothelial mitogen, however, remains controversial. VEGF189 is
      almost entirely bound to the cell surface or extracellular matrix, and is
      considered active after its cleavage and release from its extracellular binding
      site. In the present study, we demonstrate that VEGF189 induces endothelial cell
      proliferation and migration in vitro. The 30-60% increase observed with VEGF189
      (10 ng/ml) in HUVEC proliferation was similar to that observed with VEGF165.
      However, the proliferative effect observed with VEGF189 appeared dependent on the
      origin of the endothelial cell, since the proliferation was clearly observed with
      HUVEC but not with BAEC or capillary endothelial cells from dermis (HMEC). The
      effect of VEGF189 on endothelial cell migration was also analyzed using the wound
      healing and the Boyden chamber assays. The migration effect was observed with
      BAEC which do not proliferate with VEGF189, suggesting that different mechanisms
      are involved in proliferation and migration. In addition, VEGF189 as well as
      VEGF165 induced a 2-fold increase of Flk-1/KDR expression in HUVEC, the receptor
      involved in proliferation and migration of endothelial cells. In the Matrigel
      plug assay in vivo, both VEGF189 and 165 (100 ng/ml) increased the infiltration
      of endothelial cells. These data suggest that VEGF189 induced endothelial cell
      migration and proliferation under certain circumstances.

PMID- 15996657
TI  - Selective regulation of pain affect following activation of the opioid anterior
      cingulate cortex system.
AB  - Morphine and surgical cingulotomy, or transection of the anterior cingulate
      cortex (ACC), provides relief of chronic pain by selectively decreasing the
      affective dimension of the condition without altering sensory processing.
      Clinical reports suggest that morphine might be acting at the level of the ACC to
      alter the complex experience of pain. Therefore, the purpose of this experiment
      was to directly examine the functional role of the ACC in processing the aversive
      nature of pain induced by ligation of the L5 spinal nerve. Systemic
      administration of low dose morphine produced a selective attenuation of pain
      affect, as indicated by a decrease in the aversiveness of noxious cutaneous
      stimulation in nerve-damaged animals, with no alteration of mechanical paw
      withdrawal threshold. Supraspinally, microinjection of morphine into the ACC
      produced a selective naloxone reversible reduction in pain affect, as indicated
      by a decrease in the aversiveness of noxious cutaneous stimulation in nerve
      damaged animals, with no alteration of response to mechanical stimulation. These
      data demonstrate the central role of the ACC opioid system in selectively
      processing the aversive quality of noxious mechanical stimulation in animals with
      a persistent pain condition.

PMID- 15996658
TI  - The structure and response properties of Golgi tendon organs in control and
      hypodynamia-hypokinesia rats.
AB  - The Golgi tendon organs (GTOs) are encapsulated mechano-receptors that, in normal
      conditions, monitor via Ib afferent fibers the contractile force. A 14-day period
      of hypodynamia, absence of weight bearing and hypokinesia, and reduction of motor
      activity (HH) is known to induce changes in postural muscles such as the soleus.
      At present, there is no data available regarding the Ib afferent feedback in
      normal rats (CONT group) and in rats after a hypodynamia-hypokinesia (HH group)
      period. Consequently, the aim of our study was to determine the HH effects on the
      morphological (histochemistry on gross morphology) and electrophysiological
      properties of the GTOs in rat soleus muscle. In the histological study, nine CONT
      and nineteen HH GTOs of the soleus muscle were identified. The results
      demonstrated that HH GTOs were morphologically similar to the CONT GTOs.
      Regarding the electrophysiological study, a L2-L6 laminectomy was performed under
      deep anesthesia (sodium pentobarbital, 60 mg kg(-1)). Responses in single Ib
      fibers from the L5 dorsal root to the isometric twitch and tetanic fused
      contractions of "in-series" motor units (MUs) were recorded. Twenty-three and
      twenty-eight GTO/MU pairs were studied in the CONT and HH groups, respectively.
      In the HH group, the Ib afferent response exhibited a decrease in dynamic peak
      for the high stimulation frequencies and an increase in static sensitivity for
      all stimulation frequencies. Our results suggest that after an HH period, the
      GTOs continue to fulfil their mechano-sensory function to signal the contractile
      force but with a higher static sensitivity.

PMID- 15996659
TI  - A quantitative description of the activation and inhibition of CFTR by
      potentiators: Genistein.
AB  - The CFTR, encoded by the gene mutated in cystic fibrosis (CF) patients, is
      responsible for cAMP dependent chloride transport in epithelia. Substances that
      activate CFTR have been suggested as possible CF therapy. Most substances
      investigated so far exert a dual effect on the CFTR: low concentrations stimulate
      CFTR, whereas higher concentrations inhibit CFTR. Besides, the CFTR
      phosphorylation level determines the apparent affinity of the drug. We have
      studied the properties of genistein, the well known CFTR potentiator, by
      measuring apical membrane current on epithelia formed by cells stably transfected
      with CFTR and stimulated with different concentrations of CPTcAMP. We propose a
      quantitative model to describe the activatory and inhibitory effect of genistein,
      accounting also for the cAMP dependent activation.

PMID- 15996660
TI  - Protective role for cytosolic phospholipase A2alpha in autoimmune diabetes of
      mice.
AB  - Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) plays an important role in
      arachidonate pathway. To investigate the contribution of cPLA(2)alpha to
      autoimmune diabetes, we established non-obese diabetic (NOD) mouse, an excellent
      model for human type 1 diabetes, deficient in cPLA(2)alpha. These mice showed
      severe insulitis and a higher incidence of diabetes. In their macrophages,
      decreased prostaglandin E(2) (PGE(2)) induced by cPLA(2)alpha deficiency, and the
      increase in production of tumor necrosis factor (TNF)-alpha were observed. These
      results suggested that cPLA(2)alpha plays a protective role in progression of
      insulitis and development of autoimmune diabetes by suppression of TNF-alpha
      production from macrophages.

PMID- 15996661
TI  - STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human
      breast cancer cell.
AB  - Ets-1 is a cellular homologue of the product of the viral ets oncogene of the E26
      virus, and it functions as a tissue-specific transcription factor. It plays an
      important role in cell proliferation, differentiation, lymphoid cell development,
      transformation, angiogenesis, and apoptosis. Ets-1 controls the expression of
      critical genes involved in these processes by binding to ets binding sites
      present in the transcriptional regulatory regions. Here, we transiently
      overexpressed Ets-1 in MCF-7 and comprehensively searched for potential
      downstream targets of Ets-1 by cDNA microarray analysis. The expressions of
      several interferon-related genes including STAT1 and Nmi were augmented by the
      overexpression of Ets-1. RT-PCR and Western blotting confirmed the increase in
      the levels of STAT1 and Nmi mRNA and protein. In contrast, Ets-1 siRNA decreased
      the expression of STAT1 and Nmi proteins. As in our transient transfection
      experiments, stable overexpression of Ets-1, also increased the protein
      expression of STAT1 and Nmi in MCF-7 cells. Taken together, our results indicate
      that STAT1 and Nmi are downstream targets of Ets-1 in MCF-7 human breast cancer
      cells.

PMID- 15996663
TI  - The maize gene space is compositionally compartimentalized.
AB  - Previous investigations by Southern hybridization of cDNA with compositional DNA
      fractions showed that the majority of maize genes are located in a narrow GC
      range of DNA fragments and that the corresponding gene space was GC-richer than
      the region of the genome where zein genes are found. Here, we revisited the maize
      gene space using new data from the maize genome sequencing initiative. We found
      that the maize gene space itself is formed of two compositional compartments,
      i.e., a GC-poor and a GC-rich, characterized by a different distribution of Opie
      and Huck retrotransposons. The GC-rich compartment tends to be richer in GC-rich
      genes than the GC-poor compartment. However, the gene space compartimentalization
      of maize is much simpler than that of human.

PMID- 15996662
TI  - Inducible expression of a degradation-resistant form of p27Kip1 causes growth
      arrest and apoptosis in breast cancer cells.
AB  - The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) (p27) is an important
      regulator of cell cycle progression controlling the transition from G to S-phase.
      Low p27 levels or accelerated p27 degradation correlate with excessive cell
      proliferation and poor prognosis in several forms of cancer. Phosphorylation of
      p27 at Thr187 by cyclin E-CDK2 is required to initiate the ubiquitination
      proteasomal degradation of p27. Protecting p27 from ubiquitin-mediated
      proteasomal degradation may increase its potential in cancer gene therapy. Here
      we constructed a non-phosphorylatable, proteolysis-resistant p27 mutant
      containing a Thr187-to-Ala substitution (T187A) which is not degraded by
      ubiquitin-mediated proteasome pathway, and compared its effects on cell growth,
      cell-cycle control, and apoptosis with those of wild-type p27. In muristerone A
      inducible cell lines overexpressing wild-type or mutant p27, the p27 mutant was
      more resistant to proteolysis in vivo and more potent in inducing cell-cycle
      arrest and other growth-inhibitory effects such as apoptosis. Transduction of
      p27(T187A) in breast cancer cells with a doxycycline-regulated adenovirus led to
      greater inhibition of proliferation, more extensive apoptosis, with a markedly
      reduced protein levels of cyclin E and increased accumulation of cyclin D1,
      compared with wild-type p27. These findings support the potential effectiveness
      of a degradation-resistant form of p27 in breast cancer gene therapy.

PMID- 15996664
TI  - Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer
      effect on the growth of human malignant glioma cells.
AB  - Protein transduction therapy using poly-arginine can deliver the bioactive p53
      protein into cancer cells and inhibits the proliferation of the cells. However,
      one disadvantage of such therapy is the short intracellular half-life of the
      delivered protein. Here, we generated mutant proteins in which multiple lysine
      residues in the C-terminal were substituted by arginines. The mutant proteins
      were effectively delivered in glioma cells and were resistant to Mdm2-mediated
      ubiquitination. Moreover, the mutant proteins displayed higher transcription
      regulatory activity and powerful inhibition of the proliferation of glioma cells.
      These results suggest that ubiquitination-resistant p53 protein therapy may
      become a new effective cancer therapy.

PMID- 15996665
TI  - A continuing saga: the role of testosterone in aggression.

PMID- 15996666
TI  - Behavioral actions of neuropeptides in invertebrates: insights from Drosophila.
AB  - This review discusses recent advances in our understanding of the hormonal
      control of ecdysis behavior in Drosophila, as well as methods that can more
      generally be used in this organism to investigate the in vivo function of
      neuropeptide hormones. Ecdysis is a dedicated, vital, behavior that is used by
      arthropods at the end of each molt to shed the remains of the old exoskeleton. It
      is under the control of several interacting neuropeptide hormones, and successful
      ecdysis requires that the behavior and accompanying peripheral events occur at a
      precise time and in the correct order. The tightly controlled timing and
      concatenation of these events are due to the complex hormonal control of ecdysis,
      with several neuropeptides contributing to a particular event, and, conversely,
      one neuropeptide effecting both central as well as peripheral actions. It is for
      the analyses of this type of behavior that Drosophila can provide unique
      insights, and some of these insights are summarized here. In addition, I discuss
      more generally approaches that are available in this organism, which make it
      especially useful for investigating the hormonal control of behavior.

PMID- 15996667
TI  - Rate of increase in oxytocin dose on the outcome of labor induction.
AB  - OBJECTIVE: To compare the efficacy and safety of arithmetic and geometric
      increases in oxytocin infusion dosage during induction of labor. METHODS: A total
      of 120 pregnant women requiring induction of labor at term were randomly assigned
      to receive oxytocin at dosages increasing arithmetically or geometrically.
      Maternal demographics, labor delivery data, and newborn outcomes were compared.
      The setting was the maternity unit of the Obafemi Awolowo University Teaching
      Hospitals Complex, Ile-Ife, Nigeria. RESULTS: The mean maximum rates of oxytocin
      delivery needed to achieve adequate uterine contractions were similar in the 2
      groups (24.66+/-8.34 mU/min vs. 26.38+/-8.77 mU/min, P=0.24). Labor duration was
      significantly shorter in the geometric progression group (496.33+/-54.77 min vs.
      421.34+/-63.91 min, P<0.001). There were no differences in the rates of cesarean
      sections, vaginal deliveries, or uterine hyperstimulation, or in neonatal
      outcomes. CONCLUSION: A geometric rise in the rate of oxytocin infusion delivery
      reduced the duration of labor without affecting the rates of cesarean sections
      and uterine hyperstimulation, or newborn outcomes.

PMID- 15996668
TI  - Amniotic membrane for cervical reconstruction.
AB  - OBJECTIVE: To evaluate the use of amniotic membrane grafts in cases of vaginal
      and cervical agenesis. METHODS: Five girls with complete cervical and vaginal
      agenesis underwent cervicoplasty and vaginoplasty using amniotic membrane grafts.
      RESULT: Excellent epithelization and patency of cervix and vagina was achieved in
      all cases. CONCLUSION: Amniotic membrane may be used as an allograft in cervical
      reconstruction. It is inexpensive, readily available, of low antigenicity and
      does not necessitate repeated cervical dilatation. The performance of the
      reconstructed cervix during labor is yet to be observed. To the author's
      knowledge, this is the first series reported in the literature in which amniotic
      membrane was used for cervical reconstruction.

PMID- 15996669
TI  - Randomized controlled trial of music during kangaroo care on maternal state
      anxiety and preterm infants' responses.
AB  - The purpose of this randomized controlled trial was to investigate the influences
      of music during kangaroo care (KC) on maternal anxiety and preterm infants'
      responses. There are no experimental studies that explore the influences of
      combination of music and KC on psychophysiological responses in mother-infant
      dyads. Purposive sampling was used to recruit 30 hospitalized preterm infants
      body weight 1500 gm and over, gestational age 37 weeks and lower from two NICUs.
      Mother-infant dyads were randomly assigned to the treatment and the control group
      using permuted block randomization stratified on gender. There were 15 mother
      infant dyads in each group. Subjects in the treatment dyads listened to their
      choice of a lullaby music during KC for 60 min/section/day for three consecutive
      days. Control dyads received routine incubator care. Using a repeated measures
      design with a pretest and three posttests, the responses of treatment dyads
      including maternal anxiety and infants' physiologic responses (heart rate,
      respiratory rate, and O2 saturation) as well as behavioural state were measured.
      The results revealed that there were no significant differences between the two
      groups on infants' physiologic responses and the values were all in the normal
      range. However, infants in the treatment group had more occurrence of quiet sleep
      states and less crying (p<0.05-0.01). Music during KC also resulted in
      significantly lower maternal anxiety in the treatment group (p<0.01). Maternal
      state anxiety improved daily, indicating a cumulative dose effect. The findings
      provide evidence for the use of music during KC as an empirically-based
      intervention for bahavioural state stability and maternal anxiety in mother
      infant dyads.

PMID- 15996670
TI  - Identification of a DNA fragment that increases mitotic stability of episomal
      linear DNAs in Leishmania major.
AB  - The centromere is a specialized region of eukaryotic chromosomes, the site of
      kinetochore formation, spindle attachment and regulation of chromosome
      segregation during mitotic and meiotic cell divisions. To identify sequences
      which increase mitotic stability and/or act as potential centromeres in
      Leishmania major, we first generated libraries of Leishmania linear artificial
      chromosomes (LACs) bearing 30 kb inserts of randomly selected genomic DNAs. These
      were introduced into parasites, and then their stability was assessed following a
      period of 10 passages of growth in the absence of selective pressure.
      Approximately 80% of the 108 transfectants tested lost their LACs promptly and
      only 20% of the recombinants were retained; of these six showed strong but
      partial stability (maintained in 30-46% of cells). Mapping and sequencing of one
      clone (cSC10), which confers the highest degree of maintenance, revealed the
      presence of a sequence that was found within another stable episome, and which is
      dispersed in the genome of L. major. The implications of these data to the
      possible mechanisms of chromosomal maintenance are discussed.

PMID- 15996671
TI  - Associations of plasma 8-isoprostane levels with the presence and extent of
      coronary stenosis in patients with coronary artery disease.
AB  - Oxidative stress may play a role in the development of atherosclerosis. The
      purpose of the present study was to explore the relationship between 8
      isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) levels and the presence of
      coronary artery disease (CAD) and to also clarify whether 8-iso-PGF(2alpha) might
      add independently to measures of CAD extent. The study group consisted of 241
      consecutive patients who were undergoing coronary angiography for suspected CAD.
      8-iso-PGF(2alpha) levels were recorded for all participants. The analysis
      revealed a significant difference in 8-iso-PGF(2alpha) levels in patients with
      and without hypertension (P<0.001), in patients with diabetes relative to
      nondiabetic patients (P<0.05), and in males respect to females (P<0.001). A
      significant positive correlation was found between age and 8-iso-PGF(2alpha)
      levels (P<0.001). 8-iso-PGF(2alpha) levels correlated with the number of
      cardiovascular risk factors (P<0.001). 8-iso-PGF(2alpha) levels were higher in
      the CAD(+) respect to the CAD(-) groups (337.7+/-80.2 and 263.8+/-74.2 pg/ml and
      P<0.001). A stepwise elevation in the 8-iso-PGF(2alpha) levels was found
      depending on the number of affected vessels (P<0.001). The 8-iso-PGF(2alpha)
      levels showed a significant positive correlation with the numbers of >50 and >25%
      stenotic segments (P<0.001) and the extent score of coronary stenosis (P<0.001).
      The multivariate logistic regression analysis indicated 8-iso-PGF(2alpha) as an
      independent factor associated with CAD (odds ratio, 2.47 and P=0.001). The
      results suggested that 8-iso-PGF(2alpha) is associated with the presence of CAD
      in patients undergoing coronary angiography and is also related to the extent of
      coronary stenosis in Chinese population.

PMID- 15996672
TI  - Loss of natural killer cell activity in patients with coronary artery disease.
AB  - BACKGROUND: Natural killer (NK) cells are important components of the innate
      immune system and have a potential role in the regulation of autoimmunity. In the
      present study, we evaluated the NK cells in patients with coronary artery disease
      (CAD) and related the findings to clinical and laboratory parameters of the
      disease. METHODS AND RESULTS: We studied 45 patients with acute coronary syndrome
      (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and
      50 healthy controls. The distribution of NK cell subsets was determined by flow
      cytometry and NK cell-mediated cytotoxicity was quantified ex vivo. Both ACS and
      SA patients had significantly reduced numbers of CD56(dim) NK cells compared with
      controls. The patients also exhibited a significant decrease in NK cell activity.
      The loss in NK cell function was not related to inflammatory activity or
      metabolic status. CONCLUSION: Both stable and unstable conditions of CAD were
      associated with a redistribution of circulating lymphocytes, comprising a
      significant reduction of CD56(dim) NK cells and a concomitant loss of NK cell
      function. The findings suggest the presence of a persistent immune aberration in
      CAD patients independent of their clinical setting or systemic inflammatory
      state.

PMID- 15996674
TI  - Mechanical properties of spinal nerve roots subjected to tension at different
      strain rates.
AB  - An understanding of the biomechanical and physiological properties of spinal
      nerve roots, particularly in response to tension, is critical in understanding
      the pathomechanisms of pain and nerve root injury and subsequent management of
      related injuries. Biomechanical properties of dorsal nerve roots at the lumbar
      and sacral levels were evaluated at various strain rates. Nerve roots were
      stretched at two different rates, 0.01 mm/s (Group A, quasistatic) and 15 mm/s
      (Group B, dynamic). Load, displacement and digital video data were obtained as
      the nerve roots were stretched until failure. Maximum stress, strain at maximum
      stress and modulus of elasticity (E) were calculated from the load-displacement
      measurements. Comparison of mechanical properties and failure patterns of nerve
      roots at two different rates revealed significant differences. Maximum load,
      maximum stress and E values of 5.7+/-2.7 gm, 257.9+/-111.3 kPa and 1.3+/-0.8 MPa
      were observed for Group A and 13.9+/-7.5 gm, 624.9+/-306.8 kPa and 2.9+/-1.5 MPa
      were observed for Group B, respectively. Higher maximum load, maximum stress and
      E values occurred at the dynamic stretch rate as compared to the quasistatic
      stretch rate, illustrating the strain-rate dependency of spinal nerve roots. No
      differences were observed in the strain values. Differences in mechanical
      behavior of nerve roots were also observed among the four root levels (L4-S1). A
      significant interaction effect was observed between nerve root diameter and
      stretch rates. Overall, results from the present study demonstrate viscoelastic
      material properties of spinal nerve roots and provide better insight on the
      tensile properties of nerve roots at different strain rates.

PMID- 15996675
TI  - A reproducible method for studying three-dimensional knee kinematics.
AB  - The methods used in movement analysis often rely on the definition of joint
      coordinate systems permitting three-dimensional (3D) kinematics. The first aim of
      this research project was to present a functional and postural method (FP method)
      to define a bone-embedded anatomical frame (BAF) on the femur and tibia, and,
      subsequently, a knee joint coordinate system. The repeatability of the proposed
      method was also assessed. Using FP method to define the BAFs, 4 kinematic
      parameters (flexion/extension, abduction/adduction, tibial internal/external
      rotation, and antero-posterior translation) were computed for 15 subjects walking
      on a treadmill. The repeatability for all four kinematic parameters was then
      assessed, using intra- and inter-observer settings. After pooling the results for
      all observers, the mean repeatability value ranged between 0.4 degrees and 0.8
      degrees for rotation angles and between 0.8 and 2.2 mm for translation.

PMID- 15996676
TI  - Cooperative alpha-helix formation of beta-lactoglobulin induced by sodium n-alkyl
      sulfates.
AB  - It is generally assumed that folding intermediates contain partially formed
      native-like secondary structures. However, if we consider the fact that the
      conformational stability of the intermediate state is simpler than that of the
      native state, it would be expected that the secondary structures in a folding
      intermediate would not necessarily be similar to those of the native state. beta
      Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly
      high intrinsic preference for alpha-helical structure. The formation of non
      native alpha-helical intermediate of beta-lactoglobulin was induced by n-alkyl
      sulfates including sodium octyl sulfate, SOS; sodium decyl sulfate, SDeS; sodium
      dodecyl sulfate, SDS; and sodium tetradecyl sulfate, STS at special condition.
      The effect of n-alkyl sulfates on the structure of native beta-lactoglobulin at
      pH 2 was utilized to investigate the contribution of hydrophobic interactions to
      the stability of non-native alpha-helical intermediate. The addition of various
      concentrations of n-alkyl sulfates to the native state of beta-lactoglobulin (pH
      2) appears to support the stabilized form of non-native alpha-helical
      intermediate at pH 2. The m values of the intermediate state of beta
      lactoglobulin by SOS, SDeS, SDS and STS showed substantial variation. The
      enhancement of m values as the stability criterion of non-native alpha-helical
      intermediate state corresponded with increasing chain length of the cited n-alkyl
      sulfates. The present results suggest that the folding reaction of beta
      lactoglobulin follows a non-hierarchical mechanism and hydrophobic interactions
      play important roles in stabilizing the non-native alpha-helical intermediate
      state.

PMID- 15996677
TI  - Physisorbed water layer formation on fully hydroxylated mesoporous silicas.
AB  - Kinetic adsorption isotherms were obtained by gravimetric determination of water
      adsorption into fully hydroxylated mesoporous silicas using samples exposed to
      controlled humidity air at 22+/-2 degrees C. Twenty kinetic isotherms at several
      relative humidities (11, 33, 43, 51, 75, and 85%) were obtained with 11 different
      batches of silica using this simple procedure to obtain quantitative information
      on the formation of H2O adsorbates. The H2O surface concentrations obtained from
      the plateau data of individual kinetic adsorption isotherms at 43 and 51% RH,
      typically precise to about +/-1%, show that a complete monolayer is formed with
      negligible second-layer adsorption at these relative humidities. This monolayer
      has a surface concentration of 7.68+/-0.30 micromol H2O/m2, which is lower than
      the quasi-equilibrium concentration at these relative humidities obtained by the
      conventional equilibrium-isotherm procedure. Comparison with the Kiselev
      Zhuravlev concentration of silanol groups on fully hydroxylated silicas (7.6+/
      0.8 micromol SiOH/m2) confirms 1:1 H2O:SiOH stoichiometry of this monolayer. The
      presence of partial-layer structures at 2.85+/-0.1 and 5.7+/-0.1 micromol H2O/m2
      is suggested by isotherms at 11 and 33% RH, respectively, while a bilayer at
      approximately 14+/-1 micromol H2O/m2 is suggested by kinetic isotherms at 75 and
      85% RH.

PMID- 15996679
TI  - Studies of dynamic interactions between a pyrene-labeled polyelectrolyte and an
      oppositely charged rodlike micelle by a fluorescence quenching technique with use
      of a hydrophobic quencher.
AB  - Electrostatic interactions of poly(sodium 2-(acrylamido)-2
      methylpropanesulfonate) (PyPAMPS) labeled with pyrene and a rodlike micelle of
      dimethyloleylamine oxide (DMOAO), an amine oxide type surfactant, mixed with
      varying mole fractions (Y) of hexadecyltrimethylammonium chloride (CTAC), a
      cationic surfactant, were investigated by a fluorescence quenching technique
      using 3,4'-dimethylbenzophenone (DBP), a hydrophobic quencher, that can only
      reside in the micellar phase. Fluorescence measurements were performed under
      homogeneous conditions in the region 0<Y<Yp, where Yp is the critical mole
      fraction of CTAC at which macroscopic phase separation of resulting polymer
      micelle complexes occurs. There was no fluorescence quenching and hence no
      interaction occurred between PyPAMPS and the DMOAO/CTAC mixed micelle when Y was
      below a certain value (Yc) depending on the ionic strength (mu), e.g., Yc
      approximately 0.005 at mu=0.05. When Y>Yc, the fluorescence was efficiently
      quenched by DBP-carrying DMOAO/CTAC mixed micelles, both steady-state and time
      dependent fluorescence data indicating that the degree of the quenching and hence
      the extent of the complex formation increased significantly with increasing Y.
      Applying a kinetic model to the steady-state and time-dependent fluorescence
      data, the residence time for PyPAMPS in the polymer-micelle complex was
      calculated. The residence time was found to depend on both Y and mu, e.g., when Y
      was increased from 0.01 to 0.03, the residence time increased from 4 to 80 mus at
      mu=0.05 whereas little or no increase in the residence time was observed in this
      range of Y at mu=0.20. At this higher ionic strength, the residence time
      increased only moderately from 3 to 10 mus when Y was increased from 0.01 to
      0.09.

PMID- 15996678
TI  - Calculation of the dynamic impedance of the double layer on a planar electrode by
      the theory of electrokinetics.
AB  - Applications of microelectromechanical systems in the biotechnological arena
      (bioMEMS) are a subject of great current interest. Accurate calculation of
      electric field distribution in these devices is essential to the understanding
      and design of processes such as dielectrophoresis and AC electroosmosis that
      drive MEMS-based devices. In this paper, we present the calculation of the
      electrical double-layer impedance (Z(el)) of an ideally polarizable plane
      electrode using the standard model of colloidal electrokinetics. The frequency
      variation of the electrical potential drop across the double layer above a planar
      electrode in a general electrolyte solution is discussed as a function of the
      electrode zeta potential zeta, the Debye length kappa(-1), the electrolyte
      composition and the bulk region thickness L.

PMID- 15996680
TI  - Comparing fixed- and randomized-interval spaced retrieval in anomia treatment.
AB  - Spaced retrieval (SR) has recently been modified to target anomia in persons with
      aphasia (PWA). It relies on a strict management of the inter-stimulus interval
      (ISI) where the time between stimulus presentations is doubled or halved based on
      response accuracy. Although SR is successful in treating anomia, it remains to be
      studied whether the strict ISI management is necessary. The present study
      compared fixed-interval spaced retrieval (FISR) to randomized-interval spaced
      retrieval (RISR) in anomia treatment. Using alternating treatments single subject
      design, three PWA were trained to name 30 target items. Although both treatments
      were successful, the present data did not reveal one approach as superior even
      though fewer FISR sessions were needed and more FISR items were maintained on the
      post-treatment probes. This difference was only minimal suggesting that a less
      stringent stimulus schedule, as used in RISR, is sufficient for successful
      treatment outcome. LEARNING OUTCOMES: Readers will be able to describe the spaced
      retrieval treatment approach using both fixed- and randomized-interval stimulus
      schedules, as well as applications of this technique in the treatment of anomia
      in aphasia.

PMID- 15996681
TI  - Myoglobin immunoassay based on metal particle-enhanced fluorescence.
AB  - Enhanced fluorescence on silver island films (SIFs) is utilized to develop a
      sandwich-format immunoassay for the cardiac marker myoglobin (Myo). Myoglobin was
      first captured on surfaces coated with anti-Myo antibodies; the surface was then
      incubated with fluorescently labeled anti-Myo antibodies. The system was examined
      on glass surfaces and on SIFs. We observed the enhancement of the signal from
      SIFs in the range of 10-15-fold if compared to the signal from the glass
      substrate not modified with a SIF. A kinetic immunoassay for Myo on SIF-modified
      surface results in a decreased background signal. The initial results show that
      it is possible to detect Myoglobin concentrations below 50 ng/mL, which is lower
      than clinical cut-off for Myoglobin in healthy patients. We suggest the use of
      SIF-modified substrates for increasing the sensitivity of surface assays with
      fluorescence detection.

PMID- 15996682
TI  - Consequences of forward translation of the point of force application for the
      mechanics of running.
AB  - In running humans, the point of force application between the foot and the ground
      moves forwards during the stance phase. Our aim was to determine the mechanical
      consequences of this 'point of force translation' (POFT). We modified the planar
      spring-mass model of locomotion to incorporate POFT, and then compared spring
      mass simulations with and without POFT. We found that, if leg stiffness is
      adjusted appropriately, it is possible to maintain very similar values of peak
      vertical ground reaction force (GRF), stance time, contact length and vertical
      centre of mass displacement, whether or not POFT occurs. The leg stiffness
      required to achieve this increased as the distance of POFT increased. Peak
      horizontal GRF and mechanical work per step were lower when POFT occurred. The
      results indicate that the lack of POFT in the traditional spring-mass model
      should not prevent it from providing good predictions of peak vertical GRF,
      stance time, contact length and vertical centre of mass displacement in running
      humans, if an appropriate spring stiffness is used. However, the model can be
      expected to overestimate peak horizontal GRF and mechanical work per step. When
      POFT occurs, the spring stiffness in the traditional spring-mass model is not
      equivalent to leg stiffness. Therefore, caution should be exercised when using
      spring stiffness to understand how the musculoskeletal system adapts to different
      running conditions. This can explain the contradictory results in the literature
      regarding the effect of running speed on leg stiffness.

PMID- 15996683
TI  - Food-web formation with recursive evolutionary branching.
AB  - A reaction-diffusion model describing the evolutionary dynamics of a food-web was
      constructed. In this model, predator-prey relationships among organisms were
      determined by their position in a two-dimensional phenotype space defined by two
      traits: as prey and as predator. The mutation process is expressed with a
      diffusion process of biomass in the phenotype space. Numerical simulation of this
      model showed co-evolutionary dynamics of isolated phenotypic clusters, including
      various types of evolutionary branching, which were classified into branching as
      prey, branching as predators, and co-evolutionary branching of both prey and
      predators. A complex food-web develops with recursive evolutionary branching from
      a single phenotypic cluster. Biodiversity peaks at the medium strength of the
      predator-prey interaction, where the food-web is maintained at medium biomass by
      a balanced frequency between evolutionary branching and extinction.

PMID- 15996684
TI  - A crumpled surface having transverse attractive interactions as a simplified
      model with biological significance.
AB  - Using extensive analogical simulations with square sheets of paper we investigate
      the influence of short-range transverse attractive interactions on the packing
      properties of a crumpled surface. These interactions are due to transverse
      connections or local bridges associated with a given number of binding sites
      localized on the two-dimensional surface and distributed in several patterns in
      the three-dimensional physical space. Geometrical relations and critical
      exponents describing the statistical properties of the crumpled surface are
      obtained as a function of the strength of the attractive interactions. Our model
      suggests how the presence of short-range interactions as, e.g. van der Waals
      forces can be important for the geometric plasticity of biological molecules,
      which in turn is important for biological function. The relevance of our results
      to the study of molecular conformation of proteins and membranes is discussed,
      and a comparison is also made between the behavior of the crumpled surface
      studied here and other important non-equilibrium fractal structures.

PMID- 15996685
TI  - Phytoestrogenic effects of black tea extract (Camellia sinensis) in an
      oophorectomized rat (Rattus norvegicus) model of osteoporosis.
AB  - The adverse side effects of currently available anti-osteoporotic agents warrant
      the search for compounds with less toxic effects. In this study, we assessed the
      phytoestrogenic potentiality of whole aqueous extract of black tea (BTE) in a
      bilaterally oophorectomized rat model (2.5%, 1 ml/100 g body weight/day for 28
      days). Although the supplementation was given for 28 days but, sign of revival of
      copulation period (estrous stage) from non-receptive diestrous stage was first
      noticed after 21 days of BTE supplementation in bilaterally oophorectomized rats.
      This was accompanied by a significant increase in serum estradiol level. To test
      whether this increase in serum estradiol level could have an influence upon the
      oophorectomy-induced damage of bone, we assessed marker parameters of bone
      resorption and osteoclastic activity (tartrate-resistant acid phosphatase),
      collagen degradation (urinary hydroxyproline), bone loss (bone ash mineral
      content) and bone breaking strength (bone density). Results indicated that
      increase in serum estradiol level after BTE supplementation could significantly
      diminish oophorectomy-induced decaying changes in bone. This study proposes that
      aqueous BTE may be assessed as a phytoestrogenic compound for prevention against
      estrogen deficiency-related osteoporotic damages.

PMID- 15996686
TI  - Kinetic difference of berberine between hippocampus and plasma in rat after
      intravenous administration of Coptidis rhizoma extract.
AB  - In order to investigate the pharmacokinetics of berberine in Coptidis rhizoma
      extract in rat hippocampus and plasma, a simple and accurate high-performance
      liquid chromatography method was employed in this study. Berberine was determined
      using a Hypersil C(18) column with an isocratic mobile phase of acetonitrile-0.05
      M potassium dihydrogen phosphate (containing 0.5% triethylamine, pH 3.0) and with
      UV detection at 236 nm. The lower limit of quantification for berberine in both
      hippocampus and plasma was 24 ng/ml, and the lowest concentrations of berberine
      determined in rat hippocampus and plasma samples were 30.7 ng/ml at 48 h and 38.5
      ng/ml at 4 h, respectively. The calibration curve for berberine was linear over
      the concentration range 24--6000 ng/ml. At this concentration range, the overall
      recoveries (90.6--94.2%) for berberine were determined and the accuracy of intra-
      and inter-day assays from rat samples were less than 7% RSD. Following
      intravenous administration of C. rhizoma extract at a dose of 10.2 mg/kg
      containing 3 mg/kg berberine, berberine in the plasma eliminated rapidly (t(1/2
      beta)=1.13 h). However, berberine in the hippocampus increased rapidly (t(1/2
      alpha)=0.215 h), peaked at 3.67 h with a concentration of 272 ng/g, and had a
      slow elimination rate (t(1/2 beta)=12.0 h), which suggests that berberine could
      have a direct action on neuron and accumulate in the hippocampus. This study
      first showed the pharmacokinetic characteristics of berberine in rat hippocampus
      and the kinetic characteristics of berberine are dissimilar in the hippocampus
      and plasma.

PMID- 15996687
TI  - NF-kappaB and Hsp70 are involved in the phospholipase Cgamma1 signaling pathway
      in colorectal cancer cells.
AB  - The majority of deaths from colorectal cancer are due to tumor invasion and
      metastasis. Induced migration of tumor cell is generally considered to be one
      critical step in cancer progression to the invasive and metastatic stage.
      Phospholipase Cgamma1 (PLCgamma1) is a key molecular switch in the process. But,
      the mechanism and function of PLCgamma1 in colorectal cancer motility are
      unclear. We showed first in this report that epidermal growth factor (EGF)
      stimulated the phosphorylation of PLCgamma1 in human colorectal cancer cell line
      LoVo. Inhibition of PLCgamma1 with the pharmacologic agent U73122 decreased the
      migration of LoVo cells in a dose-dependent manner while EGF treatment reversed
      it partially. PLCgamma1 signaling pathway also upregulated the activity of NF
      kappaB. Furthermore, expression of Hsp70 was increased by treatment with U73122
      or pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor. These data
      indicated that PLCgamma1 played a pivotal role in the migration of human
      colorectal cancer cell and first demonstrated that upregulation of NF-kappaB
      binding activity and downregulation of Hsp70 expression were PLCgamma1-dependent
      in LoVo cells.

PMID- 15996688
TI  - Lack of involvement of dopamine and serotonin during the orphanin FQ/Nociceptin
      (OFQ/N)-induced prolactin secretory response.
AB  - The purpose of these studies was to examine possible mechanisms of Orphanin
      FQ/Nociceptin (OFQ/N)-induced prolactin release. We investigated the involvement
      of the dopaminergic neurons by quantifying DOPAC:DA levels in the median eminence
      and neurointermediate lobe following central administration of OFQ/N to female
      Sprague-Dawley rats. To specifically determine the involvement of the
      tuberoinfundibular dopaminergic neurons, immunocytochemical studies were
      conducted to visualize c-fos protein expression in the arcuate nucleus following
      central administration of OFQ/N. In addition, the role of serotonergic activation
      was examined in dose response studies using the selective serotonin antagonist
      ritansarin and the nonselective antagonist metergoline. Finally, the
      pharmacological specificity of the prolactin response was examined by pretreating
      animals with [Nphe1] NC (1-13)NH2, a drug reported to antagonize OFQ/N effects.
      The results of these studies indicate that the increase in prolactin release
      following central administration of OFQ/N does not inhibit tuberoinfundibular,
      tuberohypophyseal or periventricular hypophysial dopaminergic neuronal activity
      at 10 min after drug administration, a time when prolactin levels were
      significantly elevated. Furthermore, serotonergic activation is not involved
      since pharmacological blockade of serotonergic receptors did not alter the
      prolactin secretory response to OFQ/N. NC (1-13)NH2 did not antagonize the
      stimulatory effects of OFQ/N on prolactin secretion. The neural effects of OFQ/N
      on dopaminergic neuronal activity may occur following a different time course
      than that of the prolactin increase.

PMID- 15996690
TI  - 4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents
      with diverse selectivity profiles towards metabotropic and ionotropic glutamate
      receptor subtypes.
AB  - 4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high
      potency and selectivity at ionotropic and metabotropic glutamic acid receptor
      (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are
      valuable pharmacological tools for neuropharmacological studies, and the series
      of 4-alkyl-HIBO analogues have been extended in this paper in the search for
      versatile agents. Pharmacological characterization of five new analogues,
      branched and unbranched 4-alkyl-HIBO analogues, have been carried out. The
      present compounds are all weak antagonists at Group I mGluRs (mGluR1 and 5)
      presenting only small differences in potencies (Ki values ranging from 89 to 670
      microM). Affinities were studied at native and cloned iGluRs, and the compounds
      described show preference for the AMPA receptor subtypes GluR1 and 2 over GluR3
      and 4. However, compared to previous 4-alkyl-HIBO analogues, these compounds show
      a remarkably high affinity for the Kain preferring subtype GluR5. The observed
      GluR5 affinities were either similar or higher compared to their GluR1 and 2
      affinity. Isopropyl-HIBO showed the highest affinity for GluR5 (Ki=0.16 microM),
      and represents a unique compound with high affinity towards the three subtypes
      GluR1, 2 and 5. In general, these compounds represent new selectivity profiles
      compared to previously reported Glu receptor analogues.

PMID- 15996691
TI  - Surplus dietary tryptophan reduces plasma cortisol and noradrenaline
      concentrations and enhances recovery after social stress in pigs.
AB  - Social stress occurs in intensive pig farming due to aggressive behavior. This
      stress may be reduced at elevated dietary levels of tryptophan (TRP). In this
      study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to
      large neutral amino acid (LNAA) ratios on behavior and stress hormones in
      catheterized pigs ( approximately 50 kg BW), which were exposed to social stress
      by placing them twice into the territory of a dominant pig ( approximately 60 kg)
      for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6
      micromol/l (p<0.01) in pigs on the high vs. normal TRP diets, respectively. Pre
      stress plasma cortisol and noradrenaline concentrations were twofold (p<0.01) and
      1.4-fold (p<0.05) lower but plasma adrenaline concentration was similar in pigs
      on the high vs. normal TRP diets, respectively. During the social confrontations,
      pigs on the high vs. normal TRP diets show a tendency towards reduced active
      avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, p<0.1) but their physical
      activity (8.5+/-0.6 vs. 10.2+/-0.8 min) and aggressive attitude towards the
      dominant pig (11+/-3 vs. 7+/-2 times biting) were similar. Immediate (+5 min)
      post-stress plasma cortisol, noradrenaline and adrenaline responses were similar
      among dietary groups. After the social confrontations, the post-stress plasma
      cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min
      to 2 h) were lower/steeper (p<0.05) in pigs on the high vs. normal TRP diets. In
      summary, surplus TRP in diets for pigs (1) does not significantly affect behavior
      when exposed to social stress, (2) reduces basal plasma cortisol and
      noradrenaline concentrations, (3) does not affect the immediate hormonal response
      to stress, and (4) reduces the long-term hormonal response to stress. In general,
      pigs receiving high dietary TRP were found to be less affected by stress.

PMID- 15996692
TI  - Physiological and behavioral responses to interleukin-1beta and LPS in
      vagotomized mice.
AB  - It is well established that peripheral administration of interleukin-1 (IL-1) and
      lipopolysaccharide (LPS) can activate the hypothalamo-pituitary-adrenocortical
      (HPA) axis, alter brain catecholamine and indoleamine metabolism, and affect
      behavior. However, the mechanisms of these effects are not fully understood.
      Stimulation of afferents of the vagus nerve has been implicated in the induction
      of Fos in the brain, changes in body temperature, brain norepinephrine, and some
      behavioral responses. In the present study, the IL-1beta- and LPS-induced changes
      in certain behaviors, HPA axis activation, and catecholamine and indoleamine
      metabolism were studied in mice following subdiaphragmatic vagotomy. IL-1beta and
      LPS induced the expected decreases in sweetened milk, food intake, and locomotor
      activity, and the responses to IL-1beta, but not LPS, were slightly attenuated in
      vagotomized mice. Subdiaphragmatic vagotomy also attenuated the IL-1beta- and LPS
      induced increases in plasma ACTH and corticosterone, but the attenuations of the
      responses to IL-1beta were only marginally significant. There were also slight
      reductions in the responses in catecholamine and serotonin metabolism, and the
      increases in brain tryptophan in several brain regions. These results indicate
      that the vagus nerve is not the major pathway by which abdominal IL-1beta and LPS
      effect behavioral, HPA and brain catecholamine and indoleamine responses in the
      mouse. These results resemble those we observed in subdiaphragmatically
      vagotomized rats, but in that species the subdiaphragmatic vagotomy markedly
      attenuated the ACTH and corticosterone responses, and prevented the hypothalamic
      noradrenergic activation, as well as the fever. Overall the results indicate that
      the various responses to peripheral IL-1 and LPS involve multiple mechanisms
      including vagal afferents, and that there are species differences in the relative
      importance of the various mechanisms.

PMID- 15996693
TI  - Inbred mouse strain survey of sucrose intake.
AB  - Mouse strain differences for intake of sucrose and saccharin have been reported
      across studies, and some of these differences have been related to variants of
      the Tas1r3 taste receptor gene. However, several methodological concerns remain,
      including use of relatively few strains and/or a limited number of palatable
      concentrations in previous analyses. The present study examined strain
      differences in sucrose intake among 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J,
      C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD
      1) mouse strains across nine different sucrose concentrations (0.0001-20%) using
      two-bottle 24-h preference tests which controlled for sucrose concentration
      presentation effects, sucrose and water bottle positions, and measurement of
      kilocalorie intake as sucrose or chow. A/J, C57BL/6J, CD-1 and SWR/J strains
      consumed the greatest (11.6-22 ml) amount of sucrose, whereas the A/J, C57BL/10J,
      SJL/J and SWR/J strains consumed the greatest (44-56%) percentages of
      kilocalories as sucrose. The AKR/J, CBA/J, C3H/HeJ and DBA/2J strains consumed
      the least (6.9-7.9 ml) amount of sucrose, and displayed lower (20-30%)
      percentages of kilocalories consumed as sucrose. Whereas A/J, C57BL/6J,
      C57BL/10J, CD-1, SWR/J and SJL/J strains all displayed the most pronounced
      compensatory decreases in chow intake as the percentage of kilocalories consumed
      as sucrose increased, the AKR/J, C3H/HeJ and DBA/2J strains failed to
      significantly alter chow intake even at high sucrose concentrations. There was a
      paucity of significant correlations in the percentage of sucrose intake between
      sucrose concentrations, but percentage of sucrose intake at lower concentrations
      did correlate with previous descriptions of saccharin intake and variants of the
      Tas1r3 taste receptor gene. These data demonstrate clear mouse strain differences
      across a range of measures in sucrose intake across a wide range of
      concentrations, but caution against extrapolating between extremely high and low
      concentrations. The identification of strains with diverging abilities to
      regulate kilocalorie intake when presented with high sucrose concentrations may
      lead to the successful QTL mapping of this trait.

PMID- 15996694
TI  - Dietary restraint and US devaluation predict evaluative learning.
AB  - Previous research has indicated that flavor-flavor learning is impaired in
      restrained eaters. In Experiment 1 we sought to extend this finding using a
      larger sample and a more comprehensive assessment of dietary behavior.
      Participants (N=90, including 30 current dieters) sampled three novel flavors
      (CSs), each on 10 separate occasions, in a randomized order. Each flavor was
      paired with chocolate (US) either 10%, 50%, or 90% of the time. We then assessed
      liking for the three CSs and asked participants to complete the DEBQ-restraint
      and TFEQ-disinhibition sub-scales. After these CS-US parings, restrained eaters
      tended to prefer the 10% paired flavor whereas unrestrained eaters tended to
      prefer the 90% paired flavor. Differential CS liking was not evident in dieters
      and it was not predicted by disinhibition. Using a similar methodology, in
      Experiment 2 (N=76) we assessed evaluative change following picture-sweet
      pairings. Relative to the other CSs, the restrained eaters reported a greater
      increase in their liking for the 10% paired CS and the unrestrained eaters
      reported a greater increase in their liking for the 90% paired CS. We also
      discovered that evaluative change is related to the level of US devaluation that
      takes place during conditioning. Evidence that a sweet US can bring about a
      decrease in liking has not been reported previously. One interpretation is that
      negative beliefs and attitudes can contaminate the representation of the US
      during training.

PMID- 15996695
TI  - Commercially processed dry ginger (Zingiber officinale): composition and effects
      on LPS-stimulated PGE2 production.
AB  - Using techniques previously employed to identify ginger constituents in fresh
      organically grown Hawaiian white and yellow ginger varieties, partially purified
      fractions derived from the silica gel column chromatography and HPLC of a
      methylene chloride extract of commercially processed dry ginger, Zingiber
      officinale Roscoe, Zingiberaceae, which demonstrated remarkable anti-inflammatory
      activity, were investigated by gas chromatography-mass spectrometry. In all, 115
      compounds were identified, 88 with retention times (R(t)) >21 min and 27 with <21
      min. Of those 88 compounds, 45 were previously reported by us from fresh ginger,
      12 are cited elsewhere in the literature and the rest (31) are new: methyl [8]
      paradol, methyl [6]-isogingerol, methyl [4]-shogaol, [6]-isoshogaol, two 6
      hydroxy-[n]-shogaols (n=8 and 10), 6-dehydro-[6]-gingerol, three 5-methoxy-[n]
      gingerols (n=4, 8 and 10), 3-acetoxy-[4]-gingerdiol, 5-acetoxy-[6]-gingerdiol
      (stereoisomer), diacetoxy-[8]-gingerdiol, methyl diacetoxy-[8]-gingerdiol, 6-(4'
      hydroxy-3'-methoxyphenyl)-2-nonyl-2-hydroxytetrahydropyran, 3-acetoxydihydro-[6]
      paradol methyl ether, 1-(4'-hydroxy-3'-methoxyphenyl)-2-nonadecen-1-one and its
      methyl ether derivative, 1,7-bis-(4'-hydroxy-3'-methoxyphenyl)-5-methoxyheptan-3
      one, 1,7-bis-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxy-5-acetoxyheptane, acetoxy-3
      dihydrodemethoxy-[6]-shogaol, 5-acetoxy-3-deoxy-[6]-gingerol, 1-hydroxy-[6]
      paradol, (2E)-geranial acetals of [4]- and [6]-gingerdiols, (2Z)-neral acetal of
      [6]-gingerdiol, acetaldehyde acetal of [6]-gingerdiol, 1-(4-hydroxy-3
      methoxyphenyl)-2,4-dehydro-6-decanone and the cyclic methyl orthoesters of [6]-
      and [10]-gingerdiols. Of the 27 R(t)<21 min compounds, we had found 5 from fresh
      ginger, 20 others were found elsewhere in the literature, and two are new: 5-(4'
      hydroxy-3'-methoxyphenyl)-pent-2-en-1-al and 5-(4'-hydroxy-3'-methoxyphenyl)-3
      hydroxy-1-pentanal. Most of the short R(t) compounds are probably formed by
      thermal degradation during GC (which mimics cooking) and/or commercial drying.
      The concentrations of gingerols, the major constituents of fresh ginger, were
      reduced slightly in dry ginger, while the concentrations of shogaols, the major
      gingerol dehydration products, increased.

PMID- 15996696
TI  - Gene-environment interaction and biological monitoring of occupational exposures.
AB  - Biological monitoring methods and biological limit values applied in occupational
      and environmental medicine have been traditionally developed on the assumption
      that individuals do not differ significantly in their biotransformation
      capacities. It has become clear, however, that this is not the case, but wide
      inter-individual differences exist in the metabolism of chemicals. Integration of
      the data on individual metabolic capacity in biological monitoring studies is
      therefore anticipated to represent a significant refinement of the currently used
      methods. We have recently conducted several biological monitoring studies on
      occupationally exposed subjects, which have included the determination of the
      workers' genotypes for the metabolic genes of potential importance for a given
      chemical exposure. The exposure levels have been measured by urine metabolites,
      adducts in blood macromolecules, and cytogenetic alterations in lymphocytes. Our
      studies indicate that genetic polymorphisms in metabolic genes may indeed be
      important modifiers of individual biological monitoring results of, e.g., carbon
      disulphide and styrene. The information is anticipated to be useful in insuring
      that the workplace is safe for everyone, including the most sensitive
      individuals. This knowledge could also be useful to occupational physicians,
      industrial hygienists, and regulatory bodies in charge of defining acceptable
      exposure limits for environmental and/or occupational pollutants.

PMID- 15996697
TI  - Population variability in biological adaptive responses to DNA damage and the
      shapes of carcinogen dose-response curves.
AB  - Carcinogen dose-response curves for both ionizing radiation and chemicals are
      typically assumed to be linear at environmentally relevant doses. This assumption
      is used to ensure protection of the public health in the absence of relevant dose
      response data. A theoretical justification for the assumption has been provided
      by the argument that low dose linearity is expected when an exogenous agent adds
      to an ongoing endogenous process. Here, we use computational modeling to evaluate
      (1) how two biological adaptive processes, induction of DNA repair and cell cycle
      checkpoint control, may affect the shapes of dose-response curves for DNA
      damaging carcinogens and (2) how the resulting dose-response behaviors may vary
      within a population. Each model incorporating an adaptive process was capable of
      generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and
      threshold responses. Monte Carlo analysis suggested that all these dose-response
      behaviors could coexist within a population, as the spectrum of qualitative
      differences arose from quantitative changes in parameter values. While this
      analysis is largely theoretical, it suggests that (a) accurate prediction of the
      qualitative form of the dose-response requires a quantitative understanding of
      the mechanism, (b) significant uncertainty is associated with human health risk
      prediction in the absence of such quantitative understanding and (c) a stronger
      experimental and regulatory focus on biological mechanisms and interindividual
      variability would allow flexibility in regulatory treatment of environmental
      carcinogens without compromising human health.

PMID- 15996698
TI  - Does mechanistic understanding help in risk assessment--the example of dioxins.
AB  - Risk assessment is based on scientific information, in part on "regulatory
      toxicology", i.e., studies following protocols accepted by national or
      international authorities, and in part on fundamental scientific information
      clarifying the mechanisms of toxicity and giving a better possibility to evaluate
      also the findings of routine safety studies. Both are needed, and increased
      biological understanding increases the possibilities of handling the data in a
      rational way. In addition, risk assessment seems to include some built-in
      assumptions that are not necessarily scientific at all. This review attempts to
      highlight the distortions that are possible if we follow certain rules in a
      blinkered way not taking into consideration all aspects of the risk. The highly
      controversial risk assessment of dioxins is used to exemplify the difficulties of
      excessively straightforward risk analysis process.

PMID- 15996699
TI  - Investigation of toxic metabolites during drug development.
AB  - Adverse drug reactions (ADRs) are a significant human health problem. Any organ
      system can be affected, including the liver, skin and kidney. Drug-induced liver
      injury is the most frequent reason for the withdrawal of an approved drug from
      the market, and it also accounts for up to 50% of cases of acute liver failure.
      The clinical picture is often diverse, even for the same drug. Mild, asymptomatic
      effects occur at a relatively high frequency with a number of drugs.
      Idiosyncratic toxicity is rare but potentially life-threatening. Many serious
      ADRs that occur in man are unpredictable from routine pathology and clinical
      chemistry in laboratory animals and are therefore poorly understood. The drug
      metabolist can determine the propensity of a novel chemical entity to either
      accumulate in the hepatocyte or undergo bioactivation in numerous model systems,
      from expressed enzymes, genetically engineered cells to whole animals.
      Bioactivation can be measured using trapping experiments with model nucleophiles
      or by measurement of non-specific covalent binding. The chemistry of the process
      is defined and the medicinal chemist can address the issue by seeking a
      metabolically stable pharmacophore to replace the potential toxicophore. However,
      we require a more fundamental understanding of the role of drug chemistry and
      biochemistry in ADRs. This requires knowledge of the ultimate toxin, signalling
      in cell defense and the sequence of molecular events, which ultimately lead to
      cell and tissue damage. It is imperative that such studies have a clinical level,
      but then translated into laboratory-based molecular studies. This will provide a
      deeper understanding of potential toxicophores for drug design and define
      candidate genes for pharmacogenomic approaches to individualized medicines.

PMID- 15996700
TI  - Arsenic, mode of action at biologically plausible low doses: what are the
      implications for low dose cancer risk?
AB  - Arsenic is an established human carcinogen. However, there has been much
      controversy about the shape of the arsenic response curve, particularly at low
      doses. This controversy has been exacerbated by the fact that the mechanism(s) of
      arsenic carcinogenesis are still unclear and because there are few satisfactory
      animal models for arsenic-induced carcinogenesis. Recent epidemiological studies
      have shown that the relative risk for cancer among populations exposed to <or=60
      ppb As in their drinking water is often lower than the risk for the unexposed
      control population. We have found that treatment of human keratinocyte and
      fibroblast cells with 0.1 to 1 microM arsenite (As(III)) also produces a low dose
      protective effect against oxidative stress and DNA damage. This response includes
      increased transcription, protein levels and enzyme activity of several base
      excision repair genes, including DNA polymerase beta and DNA ligase I. At higher
      concentrations (> 10 microM), As induces down-regulation of DNA repair, oxidative
      DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic
      agent is known as hormesis and is characteristic of many agents that induce
      oxidative stress. A mechanistic model for arsenic carcinogenesis based on these
      data would predict that the low dose risk for carcinogenesis should be sub
      linear. The threshold dose where toxicity outweighs protection is hard to predict
      based on in vitro dose response data, but might be estimated if one could
      determine the form (metabolite) and concentration of arsenic responsible for
      changes in gene regulation in the target tissues.

PMID- 15996701
TI  - Genetic incorporation of HSV-1 thymidine kinase into the adenovirus protein IX
      for functional display on the virion.
AB  - Adenoviral vectors have been exploited for a wide range of gene therapy
      applications. Direct genetic modification of the adenovirus capsid proteins has
      been employed to achieve alteration of vector tropism. We have defined the
      carboxy-terminus of the minor capsid protein pIX as a locus capable of presenting
      incorporated ligands on the virus capsid surface. Thus, we sought to exploit the
      possibility of incorporating functional proteins at pIX. In our current study, we
      incorporated the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) within
      pIX to determine if a larger protein of this type could retain functionality in
      this context. Our study herein clearly demonstrates our ability to rescue viable
      adenoviral particles that display functional HSV-1 TK as a component of their
      capsid surface. DNA packaging and cytopathic effect were not affected by this
      genetic modification to the virus, while CAR-dependent binding was only
      marginally affected. Using an in vitro [3H]-thymidine phosphorylation assay, we
      demonstrated that the kinase activity of the protein IX-TK fusion protein
      incorporated into adenoviral virions is functional. Analysis of cell killing
      after adenovirus infection showed that the protein IX-TK fusion protein could
      also serve as a therapeutic gene by rendering transduced cells sensitive to
      gancyclovir. Using 9-[4-[18F]-fluoro-3-(hydroxymethyl)butyl]guanine ([18F]-FHBG;
      a positron-emitting TK substrate), we demonstrated that we could detect specific
      cell binding and uptake of adenoviral virions containing the protein IX-TK fusion
      protein at 1 h post-infection. Our study herein clearly demonstrates our ability
      to rescue viable adenoviral particles that display functional HSV-1 TK as a
      component of their capsid surface. The alternative display of HSV-1 TK on the
      capsid may offer advantages with respect to direct functional applications of
      this gene product. In addition, the determination of an expanded upper limit of
      incorporable proteins on pIX highlights its unique utility as a locus for
      placement of functional vector constructs.

PMID- 15996702
TI  - Immunization against influenza A virus: comparison of conventional inactivated,
      live-attenuated and recombinant baculovirus produced purified hemagglutinin and
      neuraminidase vaccines in a murine model system.
AB  - To simulate the 2003-2004 influenza season and compare available vaccination
      methods, immunologically naive mice were immunized with: influenza A virus
      hemagglutinin (rHA) and neuraminidase (rNA) from A/Panama/2007/99 H3N2 or
      A/Fujian/411/2002 H3N2 expressed by recombinant baculovirus, chromatographically
      purified, either as single antigens (rHA or rNA) or in combination (rHArNA);
      conventional inactivated monovalent (CIV) vaccines from each heterotypic strain;
      or a live-attenuated influenza (LAV) vaccine derived from the A/Panama/2007/99
      strain. HA containing vaccines were highly immunogenic for the HA antigen, with
      no statistically significant differences among groups in the amount of homotypic
      anti-HA antibody induced. Little cross-reactive anti-HA antibody was induced by
      any vaccine, including LAV. Statistically, the greatest amount of anti-NA
      antibody was induced by the purified NA alone or in combination with purified HA;
      the least amount of anti-NA antibody was found in mice immunized with LAV or CIV.
      Immunization with vaccines immunogenic for both HA and NA resulted in an immune
      response to both surface glycoproteins that suppressed homotypic, closely related
      heterotypic infection and had a greater reduction in mPVT following an infectious
      challenge by a distantly related heterotypic strain. These studies suggest that
      vaccines immunogenic for both HA and NA offer an increased level of protection
      from influenza.

PMID- 15996703
TI  - Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as
      a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.
AB  - We have identified two N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamide
      analogs as a novel class of human immunodeficiency virus type 1 (HIV-1) entry
      inhibitors that block the gp120-CD4 interaction, using database screening
      techniques. The lead compounds, NBD-556 and NBD-557, are small molecule organic
      compounds with drug-like properties. These compounds showed potent cell fusion
      and virus-cell fusion inhibitory activity at low micromolar levels. A systematic
      study showed that these compounds target viral entry by inhibiting the binding of
      HIV-1 envelope glycoprotein gp120 to the cellular receptor CD4 but did not
      inhibit reverse transcriptase, integrase, or protease, indicating that they do
      not target the later stages of the HIV-1 life cycle to inhibit HIV-1 infection.
      These compounds were equally potent inhibitors of both X4 and R5 viruses tested
      in CXCR4 and CCR5 expressing cell lines, respectively, indicating that their anti
      HIV-1 activity is not dependent on the coreceptor tropism of the virus. A surface
      plasmon resonance study, which measures binding affinity, clearly demonstrated
      that these compounds bind to unliganded HIV-1 gp120 but not to the cellular
      receptor CD4. NBD-556 and NBD-557 were active against HIV-1 laboratory-adapted
      strains including an AZT-resistant strain and HIV-1 primary isolates, indicating
      that these compounds can potentially be further modified to become potent HIV-1
      entry inhibitors.

PMID- 15996704
TI  - Characterization of activated sludge exopolymers from various origins: a combined
      size-exclusion chromatography and infrared microscopy study.
AB  - High-pressure size-exclusion liquid chromatography and infrared microscopy were
      coupled to investigate the molecular weight and nature of extracellular polymeric
      substances (EPS) from various activated sludges. Six main families of compounds
      (proteins, polysaccharides, organic acids, lipids, mineral phases) were found
      either as a single molecule or as associations. The molecular weight of proteins
      varied from small (10 kDa) to large (600 kDa) sizes, while all polysaccharides
      were smaller than 1 kDa. Association of different molecules implied the presence
      of species large in size. The EPS chromatographic fingerprints of sludge from
      various origins remained stable in normal operating conditions, but were
      drastically modified during settling crises. In poor settling conditions, the EPS
      with smaller molecular sizes always prevailed and large polymers were
      underrepresented. The EPS identified in activated sludge were collected in a
      chemical database which provides the basis for comparison of municipal and
      industrial wastewater treatment plants (WWTP).

PMID- 15996705
TI  - Adsorption of Pb and Cd by amine-modified zeolite.
AB  - Natural zeolites, known for their excellent sorption properties towards metal
      cations, are widely used for the purification of wastewaters. The selectivity of
      clinoptilolite, a common zeolite mineral, for Pb is known to be particularly
      high, whereas its selectivity for Cd is often lower. Extraordinarily high
      sorption capacities for soft metal cations were observed in the case of thiol
      functionalized silica gels and clays. In order to enhance the zeolites' sorption
      capacity for Cd, we treated natural heteroionic and Na-clinoptilolite in aqueous
      suspensions with cysteamine and propylamine solutions and investigated the
      sorption of Cd and Pb to amine-modified zeolite by a series of batch experiments.
      Stability constants for amine sorption on all zeolite samples at room temperature
      and 50 degrees C were obtained. Partial dimerization of cysteamine explains the
      enhanced sorption of this compound. In contrast, amine treatment did not enhance
      the adsorption capacity or selectivity of the clinoptilolite towards Cd and Pb.
      Instead, the amounts of adsorbed heavy metals decreased stoichometrically with
      increasing sorption of cysteamine and propylamine. This reduction can be
      explained by the blockage of channels by amine molecules and revealed that the
      modification of zeolites with mercaptoamines does not enhance the sorption
      capacity of zeolite for Cd and Pb.

PMID- 15996706
TI  - Transport of E. coli in columns of geochemically heterogeneous sediment.
AB  - To elucidate the parameters determining the transport of Escherichia coli in
      aquifers, the attachment of E. coli in low concentrations to column sediments was
      investigated. The sediments comprised 0.18-0.50mm quartz sand, grains coated with
      goethite, calcite grains or grains of activated carbon (AC), in varying fractions
      (lambda=0, 0.05, 0.1, 0.2, 0.4, 0.7, 1.0) and all of similar diameter to the
      quartz sand. The weighted sum of favourable and unfavourable sticking
      efficiencies (alpha(total)) showed that upon increasing the fraction of
      favourable mineral grains (lambda) there was an initial rapid increase, which
      then slowed down. This was most pronounced in the AC experiments, followed by the
      calcite experiments and then the goethite experiments. We ascribe this non-linear
      relation to surface charge and hydrophobic heterogeneity of the E. coli
      population.

PMID- 15996707
TI  - Prevalence of vaccine-derived polioviruses in sewage and river water in South
      Africa.
AB  - Polioviruses (PVs) are not associated with waterborne transmission to the same
      extent as many other enteric viruses. However, they are typically transmitted by
      the faecal-oral route, which implies that the risk of infection by exposure to
      the viruses in water cannot be underestimated. The risk appears particularly high
      for rural communities, which use sewage-polluted river water for domestic
      purposes. Thus, the presence in the environment of highly evolved, neurovirulent
      vaccine-derived poliovirus (VDPV) strains in the absence of polio cases would
      have important implications for strategies to terminate immunisation with oral
      poliovirus vaccine (OPV) following global polio eradication. The aim of the
      current study was to determine the prevalence of VDPVs in selected sewage and
      river water samples collected from 2001 to 2003, and to construct phylogenetic
      trees of the partially sequenced 5'untranslated region (5'UTR) and the VP1 region
      of the genomes to deduce the genetic relatedness between the PV strains. Using
      the monolayer plaque assay, 703 plaques from sewage and 157 plaques from river
      water samples were analysed. Application of a RT-multiplex PCR revealed that 176
      of these plaques were non-polio enteroviruses, and 49 were PV isolates. The Sabin
      specific RT-triplex PCR revealed the presence of 29 Sabin PV type 1, 8 Sabin PV
      type 2 and 12 Sabin PV type 3 isolates. The 5'UTR and the VP1 region of 13 PV
      type 1, 7 PV type 3 and 6 PV type 2 isolates were partially sequenced. The
      majority of the OPV isolates (24 out of 26) displayed close sequence
      relationships (>99% VP1 sequence identity) to the parental Sabin PV vaccine
      strains and were classified as "OPV-like viruses". Two isolates (D1 08/28 and OF1
      05/21) were found to be highly divergent and were classified as "suspected"
      VDPVs. Isolate OF1 05/21 (a "suspected" VDPV type 1) showed more than 0.9%
      divergence in VP1, whereas isolate D1 08/28 (a "suspected" VDPV type 2) showed
      1.4% divergence in VP1 from the parental Sabin PV vaccine strains. As with most
      of the other OPV-like isolates, these "suspected" VDPVs were carrying mutations,
      which have previously been associated with reversion of the attenuated Sabin PV
      strains to increased neurovirulence. It was estimated that the total period of
      replication for the two "suspected" VDPVs was between 12 and 16 months. In
      conclusion, this study provided new and relevant information on the prevalence of
      "suspected" VDPVs in sewage and river water, and opened the way to assess the
      possible broader significance of the findings reported here.

PMID- 15996709
TI  - pH effect on OH radical production in photo/ferrioxalate system.
AB  - In wastewater treatment using the Fenton and photofenton processes, pH is one of
      the critical operating parameters, due to the fact that the Fenton reaction can
      work only under acidic pH conditions. It is hoped that Ferric iron complexed with
      oxalate (Fe(III)-oxalate; ferrioxalate) will provide an alternative to the
      traditional Fenton process with its limited range of pH conditions, since its
      high solubility in aqueous media can broaden the available pH range of the Fenton
      reaction up to the near neutral pH regime. In this study, we investigated the pH
      dependency of OH production in the photo/ferrioxalate system, in the presence and
      absence of externally supplied H(2)O(2), where 2,4--D was used as the probe
      compound for OH production at a wide range of pH values (1.2--7.4). In the
      absence of externally supplied H(2)O(2), the 2,4--D degradation was considerably
      enhanced with increasing pH, whereas it was reduced with increasing pH in the
      presence of an excess amount of H(2)O(2). These variations in the degradation of
      2,4--D were thus found to be precisely related to the formation of H(2)O(2), a
      factor to which little attention was paid in previous studies. In the absence of
      H(2)O(2) addition, the in situ formation of H(2)O(2) is facilitated with
      increasing pH by the reaction of Fe(II) with O(2)(-), which increases with pH,
      augmenting the production of OH and thereby leading to the faster degradation of
      2,4--D. This same reaction can also provide an explanation for the opposite pH
      dependence of 2,4--D degradation in the presence of H(2)O(2).

PMID- 15996708
TI  - Experimental analysis of coagulation of particles under low-shear flow.
AB  - The aggregation and breakup of particle flocs were investigated by monitoring the
      size distribution of a suspension of aggregates, with diameter d(o), under shear
      flow created by two mixing systems. The aggregation behavior was studied in 63
      experiments under various conditions of induced shear rate and particle volume
      concentration for particle aggregates smaller than the Kolmogorov scale. Despite
      small shear rates being characteristics of natural systems, only experiments with
      comparatively high shear rates have been conducted to date. Because of this
      reason, in this study, the shear rates were chosen to mimic those found in
      natural systems. In the first set of experiments the aggregate size, d, was
      analyzed by changing the mean shear, G (ranging from 0.70 to 27.36 s(-1)) created
      in a tank with a grid oscillating through the whole suspension volume. In the
      second set of experiments, a spherical flask was placed in an orbital shaking
      table where G ranged from 0.45 to 2.40s(-1). In all the cases there was an
      increase of d at increasing G . The dependence on d was found to be identical for
      the particle volume concentrations investigated, phi=0.2,0.8,2,4,6,8 and 10 x 10(
      5), with the stable aggregate size shifting towards aggregate growth as particle
      volume concentration increased. These results demonstrate that shear provided a
      means to keep the particle number count high for collisions to occur but it is
      small enough that the aggregation-breakup balance is dominated by aggregation.

PMID- 15996710
TI  - Application of a neural observer to phenols ozonation in water: simulation and
      kinetic parameters identification.
AB  - Presented in this study, a dynamic neural network (DNN) is employed to estimate
      the states dynamics of the phenols-ozone-water system. A new technique based on
      the dynamic neural network observer (DNNO) with relay (signum) term is applied to
      estimate the decomposition dynamics of phenols and to identify their kinetic
      parameters without any mathematical model usage. The decomposition of phenols
      (phenol (PH), 4-chlorophenol (4-CPH) and 2,4-dichlorophenol (2,4-DCPH)) and their
      mixture by ozone, realized in a semi-batch reactor, is considered as a process
      with uncertain model ("black-box"). Only one parameter monitoring, namely, the
      ozone concentration in gas phase in the reactor outlet, is measured during
      ozonation. The variation of this variable is used to obtain the summary
      characteristic curve for the phenols ozonation. Then, using the experimental
      decomposition dynamics of phenols and of their mixture, obtained by HPLC method,
      the proposed DNNO is applied to estimate the ozonation constants of phenols at
      the different pH 2-12. A good correspondence between the decomposition dynamics
      and the estimated ones by DNNO is obtained.

PMID- 15996711
TI  - Optimizing the specific surface area of fly ash-based sorbents for flue gas
      desulfurization.
AB  - High performance sorbents for flue gas desulfurization can be synthesized by
      hydration of coal fly ash, calcium sulfate, and calcium oxide. In general, higher
      desulfurization activity correlates with higher sorbent surface area.
      Consequently, a major aim in sorbent synthesis is to maximize the sorbent surface
      area by optimizing the hydration conditions. This work presents an integrated
      modeling and optimization approach to sorbent synthesis based on statistical
      experimental design and two artificial intelligence techniques: neural network
      and genetic algorithm. In the first step of the approach, the main and
      interactive effects of three hydration variables on sorbent surface area were
      evaluated using a full factorial design. The hydration variables of interest to
      this study were hydration time, amount of coal fly ash, and amount of calcium
      sulfate and the levels investigated were 4-32 h, 5-15 g, and 0-12 g,
      respectively. In the second step, a neural network was used to model the
      relationship between the three hydration variables and the sorbent surface area.
      A genetic algorithm was used in the last step to optimize the input space of the
      resulting neural network model. According to this integrated modeling and
      optimization approach, an optimum sorbent surface area of 62.2m(2)g(-1) could be
      obtained by mixing 13.1g of coal fly ash and 5.5 g of calcium sulfate in a
      hydration process containing 100ml of water and 5 g of calcium oxide for a fixed
      hydration time of 10 h.

PMID- 15996712
TI  - Water quality of the Guadiamar River after the Aznalcollar spill (SW Spain).
AB  - In April 1998, a spill of 6 hm3 of pyritic mud and acidic water was released into
      the Guadiamar River due to the rupture of the Aznalcollar tailings dam. Before
      the spill, the river was already strongly affected by acid mine drainage (AMD).
      In this study, the water quality of the Guadiamar River is analysed from a
      periodic sampling started after the spill. Previous data of the water quality
      have also been obtained. A recovery of the water quality is observed from 2002
      on. The distribution of arsenic is opposed to that of the rest of metals, with
      the lowest concentrations to the north, due to the adsorption and/or
      coprecipitation on ferric oxyhydroxides. In the southern area, when pH values are
      close to 8, arsenic desorption occurs. There is a seasonal pattern of the trace
      metal content evolution, different in the northern and southern zones of the
      river. In the northern area the highest polluting levels occur in summer, due to
      a lower dilution of the mining leachates. In the southern area, the highest metal
      levels occur during the winter, since during the summer metals remain held by
      surface sorption processes in the hyporheic zone of the river.

PMID- 15996713
TI  - Plant performance, dioxygenase-expressing rhizosphere bacteria, and
      biodegradation of weathered hydrocarbons in contaminated soil.
AB  - Two greenhouse pot experiments were conducted to investigate the potential of 13
      plant species (grasses, cruciferes, legumes, herbs) to thrive in a long-term
      contaminated soil from a former manufactured gas plant (MGP) site, to promote the
      proliferation of total and aromatic ring dioxygenase-expressing bacteria (ARDB)
      in the root zone, and to foster the biodegradation of petrol hydrocarbons (PHCs)
      and polycyclic aromatic hydrocarbons (PAHs). PHCs at 23200 mg kg(-1) and PAHs at
      2194 mg kg(-1) reduced seed germination, plant survival, and shoot yields for
      most plants. Total bacteria and ARDB were generally more abundant in contaminated
      soil and were most numerous in the rhizosphere of mustard. During 68 d, the loss
      of total petrol hydrocarbons (TPHs) and total US EPA priority PAHs (TPAHs) was
      greatest in soil planted with hemp and mustard. Pea, cress, and pansy increased
      the amounts of PAHs extracted from soil, including an almost 60% increase for
      dibenzo(ah)anthracene. Plants may enhance the chemical extractability and perhaps
      biological availability of initially unextractable molecules.

PMID- 15996714
TI  - Monitoring tricyclazole residues in rice paddy watersheds.
AB  - Pesticide application to rice paddies may affect the quality of environmental
      resources such as groundwater and surface water. The distribution of residues of
      tricyclazole, an environmentally persistent fungicide used widely in Italy, was
      monitored in the network of surface water bodies surrounding the main rice
      production area in Italy. The location of monitoring sites was based on the
      potential risk for contamination with tricyclazole. This was determined as a
      function of the area of rice grown, the geographical distribution of rice crops
      susceptible to the pest, and sales of tricyclazole. Monitoring sites were also
      located to represent different spatial scales (farm, catchment and basin). For
      water samples taken shortly after application in July and August, the highest
      concentrations of tricyclazole were measured at the farm sites. However, residues
      were also detected at the catchment and basin scale. The 95% of the measured
      residue levels was below 9.80, 1.20 and 1.15 microg l(-1), at the farm, catchment
      and basin scales, respectively. In sediment, tricyclazole residues were detected
      in 12 out 176 samples collected with the 95% of the measured residue levels below
      the concentration of 0.03 mg kg(-1). Residues were sporadically detected in
      samples taken after the crop was harvested in November and December. Variables
      such as the scale of sampling, the season and the year, were significant in
      determining pesticide residue distribution. The type of water body was less
      significant.

PMID- 15996715
TI  - Treatment of the textile wastewater by combined electrocoagulation.
AB  - Electrocoagulation (EC) due to some advantages over chemical coagulation is
      becoming a popular process to be used for wastewater treatment. The aim of this
      paper is to investigate the effect of initial addition of a chemical coagulant
      such as polyaluminum chloride (PAC) or alum on the COD removal efficiency of EC
      treatment of textile wastewaters. The two salts exhibited the same performance in
      chemical coagulation, but in the combined electrocoagulation (CEC), PAC was found
      to significantly enhance the COD removal rate and efficiency, depending on the
      amount of the total aluminum supplied, by initial addition and electrochemical
      generation. A comparative operating cost analysis was also given and it was found
      that with the same operating cost per mass of COD removed, CEC performance was
      80%, in contrast to 23% with EC, in 5 min of operation.

PMID- 15996716
TI  - Concentrations and specific loads of UV filters in sewage sludge originating from
      a monitoring network in Switzerland.
AB  - Many substances related to human activities end up in wastewater and accumulate
      in sewage sludge. The present study focuses on the analysis of widely used UV
      filters 3-(4-methylbenzylidene) camphor (4-MBC), octyl-methoxycinnamate (OMC),
      octocrylene (OC) and octyl-triazone (OT) in sewage sludge originating from a
      monitoring network in Switzerland. Mean concentrations in stabilised sludge from
      14 wastewater treatment plants were 1780, 110, 4840 and 5510 microg/kg dry matter
      for 4-MBC, OMC, OC and OT, respectively. Specific loads in sewage sludge show
      that UV filters originate mainly from private households, but surface runoff and
      industries may be considered as additional sources. This indicates that besides
      use for sunscreens and cosmetics UV filters might occur in plastics and other
      materials and be released to the environment by volatilization or leaching.
      Differences between the modeled per capita loads of UV filters in sewage sludge
      and the observed specific loads in sewage sludge are probably due to erroneous
      figures of production volumes, degradation and sorption during wastewater
      treatment as well as degradation processes during transport in the sewer or
      sludge treatment. Thus, further research is needed to elucidate the fate of UV
      filters after application and release into the environment. Other compounds used
      as UV filters should be included in future studies.

PMID- 15996717
TI  - The effects of hybridization on growth allometry and craniofacial form in
      Sulawesi macaques.
AB  - The present research investigates the effects of hybridization between Macaca
      maurus and M. tonkeana on adult male form and patterns of growth allometry.
      Comparisons of adult hybrid mean phenotypic values with the adult averages of the
      parental species indicate a condition of heterosis for cranial vault length and
      crown-rump length. Negative heterosis is indicated for body mass. Regression
      parameters describing growth allometry are generated for four craniofacial
      measurement variables and one body measurement using both least squares and
      reduced major axis regression. Comparisons of hybrid and parental regression
      slopes and intercepts using analysis of covariance and t-tests suggest that there
      is a hybrid pattern of growth allometry characterized by an increase in
      regression slope values coupled with lower intercept values compared to those of
      the parental species and the parental averages for most regression parameters.
      Multivariate analyses of the adult and ontogenetic morphometric data indicate
      significant differences across species taxa in form and shape during development
      and adulthood. Our finding of significant differences between hybrids and their
      parental taxa in growth allometry and craniofacial form and shape during
      development challenges the assumption often made regarding the reproductive and
      taxonomic significance of observed ontogenetic divergence between Neandertals and
      modern humans. We propose that anthropological primatology, with its goal of
      developing nonhuman primate models for investigating human evolution, can provide
      a biologically relevant means by which to empirically estimate the taxonomic
      significance of morphological and ontogenetic divergence observed in the hominid
      fossil record.

PMID- 15996718
TI  - The fate of experimentally deposited nitrogen in mesocosms from two Canadian
      peatlands.
AB  - In large regions of Europe and North America, peatlands have been exposed to
      elevated rates of atmospheric nitrogen (N) deposition. We investigated the fate
      of experimentally added N (NH(4)(15)NO3) at two different N loads (1.2 and 4.7 g
      N m(-2) yr(-1)) and water tables (1 and 32 cm) in intact cores from two
      peatlands, located in Central and Eastern Canada. The sites receive an estimated
      total N load of 0.6 g m(-2) a(-1) and 1.5 g m(-2) yr(-1), excluding nitrogen
      fixation. In all treatments, experimentally added nitrate (NO(3-)) was fully (96
      99%) and ammonium (NH(4+)) mostly (81-97%) retained by the plant cover, mainly
      consisting of Sphagnum mosses, or in the unsaturated zone below. However, on
      average only 48% of the (15)N were recovered from the plant cover, and
      substantial amounts were found in depth layers of 2-6 cm (21-46%) and 8-12 cm
      (1.4-10.8%) below the moss surface. The amount of (15)N retained also
      significantly decreased with a lower water table from 56+/-9% to 40+/-10%. These
      findings document a substantial mobility of N, particularly during water table
      drawdown. Analysis of (15)N by a sequential diffusion procedure revealed a
      transfer of (15)N from NO(3-) into NH(4+) and dissolved organic N (DON), but the
      contents of (15)N in these pools accounted for less than 1% of the total N,
      natural background subtracted. The mass flux of dissolved (15)N into the peat was
      small compared to the total mass flux of (15)N. The accumulation of (15)N in the
      bulk peat must have been caused by a mechanism that was not investigated,
      possibly by transport of particulate organic N.

PMID- 15996719
TI  - Mercury in ground water, septage, leach-field effluent, and soils in residential
      areas, New Jersey coastal plain.
AB  - Water samples were collected from domestic wells at an unsewered residential area
      in Gloucester County, New Jersey where mercury (Hg) concentrations in well water
      were known to exceed the USEPA maximum contaminant level (MCL) of 2,000 ng/L.
      This residential area (the CSL site) is representative of more than 70 such areas
      in southern New Jersey where about 600 domestic wells, sampled previously by
      State and county agencies, yielded water containing Hg at concentrations that
      exceed the MCL. Recent studies indicate that background concentrations of Hg in
      water from this unconfined sand and gravel aquifer system are <10 ng/L.
      Additional sampling was conducted at the CSL site in order to better understand
      sources of Hg and potential Hg transport mechanisms in the areas with Hg
      contaminated ground water. At the CSL site, concentrations of Hg were
      substantially lower (although still exceeding the MCL in some cases) in filtered
      water samples than in the unfiltered water samples collected previously from the
      same wells. Surfactants and elevated concentrations of sodium, chloride, nitrate,
      ammonium, and phosphate in water from domestic and observation wells indicated
      septic-system effects on water quality; detections of sulfide indicated localized
      reducing conditions. Hg concentrations in septage and leach-field effluent
      sampled at several other households in the region were low relative to the
      contaminant-level Hg concentrations in water from domestic wells. Relations of Hg
      concentrations in leach-field effluent to iron concentrations indicate that
      reductive dissolution of iron hydroxides in soils may release Hg to the
      percolating effluent.

PMID- 15996720
TI  - Blood lead levels in primary school children in Trinidad and Tobago.
AB  - This study is the first national baseline survey of blood lead levels (BLLs)
      conducted on primary school children (ages 5-7 years) in Trinidad and Tobago. A
      total of 1,761 students from 61 schools participated in the study over a 3-month
      period. Measurements of capillary BLLs were assessed as well as responses to a
      risk assessment questionnaire. BLLs ranged from <1 microg/dL to 28.6 microg/dL
      with a geometric mean of 2.8 microg/dL, which compared favourably with results
      from the U.S. 1991-94 National Health and Nutrition Examination Survey. Fifteen
      (0.9%) children had a BLL>or=10 microg/dL (10.8-28.6 microg/dL) of which three
      (0.2%) met the U.S. criteria for lead poisoning (BLL>or=20 microg/dL). Further
      environmental investigations are required to identify source(s) of lead exposure
      in cases with high BLL.

PMID- 15996721
TI  - Strategies to reduce hemostatic activation during cardiopulmonary bypass.
AB  - INTRODUCTION: We evaluated whether a modified protocol for cardiopulmonary bypass
      (CPB) could reduced the systemic hemostatic activation associated with this
      procedure. MATERIALS AND METHODS: The in vivo rates of thrombin, fibrin, plasmin
      and D-dimer generation were determined in each subject during CPB using measured
      levels of hemostatic factors combined with a computer model of the cardiovascular
      and hemostatic systems. A standard CPB group using uncoated circuits, standard
      heparin levels and direct shed blood reinfusion (n=9) was compared to a modified
      CPB group using heparin-coated circuits, shed blood collection, washing and
      reinfusion post-operatively, lower heparin levels and epsilon-amino-caproic acid
      (n=10). RESULTS AND CONCLUSIONS: Standard CPB increased average thrombin
      generation 9-fold, decreased fibrin generation 2-fold, increased plasmin
      generation 11-fold and increased fibrin degradation and D-dimer generation 19
      fold. During CPB in the modified group thrombin generation was not increased
      beyond surgical levels, lower heparin concentrations allowed each thrombin to
      make more fibrin prior to inhibition, while fibrin degradation was suppressed by
      epsilon-amino-caproic acid. At baseline for every 100 fibrins formed only 1-2
      were degraded to D-dimer. During standard CPB for every 100 fibrins generated on
      average 34 fibrins were degraded with some subjects showing a net fibrin loss. In
      contrast, in the modified CPB group for every 100 fibrins formed only 4 fibrins
      were degraded (p<0.0001 vs. standard group). Kinetic modeling of hemostasis in
      individual patients showed that a modified CPB protocol could reduce excessive
      thrombin generation during CPB and suppress fibrin degradation moving hemostatic
      regulation back towards normal.

PMID- 15996722
TI  - Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical
      carcinogenesis: An analysis of haplotype and gene-gene interaction.
AB  - OBJECTIVE: Whereas human papillomavirus (HPV) infection is necessary but not
      sufficient for cervical carcinogenesis, host genetic variations may confer
      individual susceptibility. Resistance to apoptosis is a hallmark of cancer in
      which FAS/FAS ligand signaling plays an important role. The present study
      examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes,
      alone or in combination, are associated with cervical carcinogenesis. METHODS:
      The genotypes of FAS -670A/G, FAS -1377G/A, and FASL -844C/T were assessed in 143
      patients with high-grade squamous intraepithelial lesions (HSIL), 175 patients
      with invasive squamous cell carcinomas (SCC), and in age-matched controls by real
      time PCR with allele-specific TaqMan probes. The status of cervical high-risk HPV
      infection was determined and adjusted to test the independence of genotype in the
      risk assessment. RESULTS: The A-allele and AA-genotype frequencies of FASA -670G
      were significantly higher in HSIL/SCC than in controls (60% vs. 54%, P = 0.04, OR
      1.26 [95% CI 1.01-1.57]; 38.0% vs. 28.6%, P = 0.02, OR 1.70 [95% CI 1.07-2.70]).
      No association between FAS -1377 or FASL -844 polymorphisms and HSIL/SCC could be
      identified. The FAS -1377A/-670A haplotype conferred a higher risk for HSIL/SCC
      (OR 3.05, 95% CI 1.28-7.30) than FAS -670A alone (OR 1.26, 95% CI 1.28-7.30). The
      interaction between FAS -670AA and FASL -844CC genotypes was associated with a
      risk of HSIL/SCC (OR 2.13, 95% CI 1.06-4.29) higher than that of the FAS -670AA
      genotype alone (OR 1.70, 95% CI 1.07-2.70). CONCLUSIONS: The FAS -1377A/-670A
      haplotype in combination with FASL -844C is associated with cervical
      carcinogenesis.

PMID- 15996723
TI  - The effects of dopaminergic/serotonergic reuptake inhibition on maternal
      behavior, maternal aggression, and oxytocin in the rat.
AB  - Studies using dopaminergic and serotonergic agonists or antagonists implicate
      involvement of these systems in various aspects of early maternal behavior and
      postpartum aggression towards an intruder in rats, both of which are associated
      with the presence of oxytocin in specific brain regions. It is unclear however,
      if or how long-term uptake inhibition of either neurotransmitter system alone or
      in combination, affects oxytocin system dynamics or maternal behavior/aggression.
      Pregnant women frequently take drugs (antidepressants, cocaine) that induce long
      term reuptake inhibition of dopamine and/or serotonin, thus it is important to
      understand these effects on behavior and biochemistry. Rat dams were treated
      throughout gestation with amfonelic acid, fluoxetine, or a combination of both,
      to investigate effects of reuptake inhibition of dopamine and serotonin systems
      respectively, on maternal behavior, aggression and oxytocin. The more appetitive
      aspects of maternal behavior (nesting, licking, touching) and activity were
      increased by the low dose of amfonelic acid, high dose of fluoxetine, or the high
      dose combination more than other treatments. Aggression was decreased by
      amfonelic acid and somewhat increased by fluoxetine. Dopamine uptake inhibition
      appears to have a strong effect on hippocampal oxytocin levels, while receptor
      dynamics may be more strongly affected by serotonin uptake inhibition.

PMID- 15996725
TI  - A new method to analyze boar sperm DNA fragmentation under bright-field or
      fluorescence microscopy.
AB  - We present a new, rapid and simple method to study DNA Fragmentation Index (DFI)
      in sperm samples from boar under bright-field and fluorescence microscopy.
      Discrimination of sperm cells containing fragmented DNA relies on the extreme
      peripheral diffusion of their chromatin fragments, whereas those sperm nuclei
      without DNA fragmentation do not disperse or show very restricted spreading of
      DNA loops close to the flagellum. The basic methodology provided in the
      commercial kit Sperm-Sus-Halomax allows, in addition to a direct estimation of
      DFI in a sperm sample under bright field microscopy, a direct visualization of
      DNA breaks by incorporation of labelled nucleotides using the DNA polymerase I
      following the in situ nick translation assay (ISNT methodology not provided in
      the kit). An external control using DBD-FISH (DNA breakage detection-fluorescence
      in situ hybridization) on human and boar sperm samples was used in this
      experiment. The results obtained show (i) low levels of background DNA
      fragmentation (from 0.7 to 10%), (ii) no significant differences for DFI after
      the application of Sperm-Sus-Halomax and ISNT, with a tendency to be
      underestimated after using DBD-FISH and (iii) a characteristic chromatin
      organization in boar sperm nucleus, with a particular response to chromatin loop
      relaxation and preferential DNA labelling by ISNT at the proximal nuclear area,
      close to the flagellum. This methodology allows the routine assessment of boar
      sperm samples for DFI, as well as basic and clinical research on this relevant
      topic in any laboratory of semen analysis.

PMID- 15996724
TI  - The airway sensory impact of nicotine contributes to the conditioned reinforcing
      effects of individual puffs from cigarettes.
AB  - Puffs from cigarettes are the fundamental unit of smoking reward. Here, we
      examined the extent to which reward from puffs can be derived from the airway
      sensory effect of nicotine, in the absence of a direct central nervous system
      effect of nicotine. We did this by assessing the self-reported reward obtained
      from individual puffs from nicotinized, denicotinized and unlit cigarettes within
      7 s of inhalation, which is before nicotine had an opportunity to reach the
      brain. We also assessed the self-reported strength of airway sensations elicited
      by the puffs. We found that nicotinized puffs were rated as both stronger and
      more rewarding than denicotinized and unlit puffs. We also found that the extent
      to which nicotine elicited reward was directly correlated with the extent to
      which nicotine elicited airway sensations. This indicates that the airway sensory
      effects of nicotine contribute to the reward from puffs, above and beyond the
      reward derived from the airway sensory effects of non-nicotine constituents.
      These findings have implications for the interpretation of studies that use puffs
      as experimental units to examine nicotine reward. They also have implications for
      the use of denicotinized and low nicotine cigarettes as aids to smoking
      cessation.

PMID- 15996726
TI  - Comparison of two methods for obtaining spermatozoa from the cauda epididymis of
      Iberian red deer.
AB  - We have compared two methods for salvaging epididymal sperm from post-mortem
      samples from Iberian red deer. Of each pair of testicles (29 samples), one cauda
      epididymis was processed by means of cuts (sperm was immediately diluted with
      extender) and the other was detached from the corpus and flushed from the vas
      deferens with 1 mL of extender. Sperm was processed for cryopreservation, and
      analyzed just after recovery, pre-freezing and post-thawing. Total spermatozoa
      recovered, contamination (concentration of epididymal cells and red blood cells
      (RBCs)) and quality (motility by CASA, and acrosomal status, viability and
      mitochondrial status by flow cytometry) were used to compare both methods. The
      number of recovered spermatozoa was similar for both methods. Contamination was
      higher for the cuts method, but when considering the final dilution before
      freezing, only RBCs concentration was significantly higher. Motility was similar
      just after extraction, but higher for both pre-frozen and post-thawed flushed
      sperm. Pre-freezing acrosomal status (P < 0.05) and viability (P < 0.1) were
      better for flushing; however post-thawing results were similar for the two
      methods. A clustering analysis using CASA data showed that the subpopulation
      pattern of motile sperm was different depending on the method, being better for
      flushing. With regard to yield, lower contamination (especially RBCs) and, in
      general, better quality results, flushing seems to be a more recommendable method
      for post-mortem sperm recovery. The cuts method may be more practical on certain
      occasions, but care must be taken in order to achieve rapid extension of the
      sample and to avoid contamination in order to improve sample condition.

PMID- 15996727
TI  - Adolescent mental health literacy: young people's knowledge of depression and
      help seeking.
AB  - This study examined the mental health literacy of a group of adolescents, with
      particular reference to their ability to recognize symptoms of depression in
      their peers. Respondents were 202 Australian adolescents (122 males, 80 females)
      aged 15-17 years. Their mental health literacy was examined through a
      questionnaire that presented them with five scenarios of young people.
      Respondents showed a mixed ability to correctly recognize and label depression,
      although they were able to differentiate depressed and non-depressed scenarios in
      terms of severity and expected recovery time. Results are discussed in light of
      findings from adult mental health literacy and clinical implications.

PMID- 15996728
TI  - The water quality of the Ria de Aveiro lagoon, Portugal: from the observations to
      the implementation of a numerical model.
AB  - Ria de Aveiro is a very important area of the Portuguese coast, which has been
      under an increasing anthropogenic pressure for several decades and, contributes
      to the degradation of the lagoon's water quality. This work presents both a
      characterisation of the water quality of the Ria de Aveiro lagoon, using
      physical, chemical and biological experimental data, and an implementation of a
      numerical model for the water quality of the lagoon. The ultimate goal is to
      obtain an accurate numerical model able to simulate major water quality features
      of the lagoon under the influence of different forcing conditions. Data analysis
      reveals good correlations between the salinity and almost all the water quality
      variables as well as between the different variables. The maximum biochemical
      oxygen demand concentration (BOD) depends on the light intensity, the temperature
      and the river inputs. The main vulnerable areas of the lagoon, from the water
      quality point of view, seem to be the far end of the main channels, where low
      dissolved oxygen concentration (DO) and high BOD concentrations are observed. The
      numerical model of the Ria de Aveiro has reproduced both winter-spring and spring
      summer events related to the lagoon water quality as well as its main pattern.
      Both data and modelling results show that the BOD5 concentrations (where the
      subscript '5' means that the BOD measurements were conducted for five days,
      without inhibitor of nitrification) are driven by the river influence, during the
      winter-spring period, and by the biological activity during the spring-summer
      period. The DO concentrations show high values in the spring-summer period and
      smaller concentrations in the winter-spring period at the far end of the lagoon.
      The application of the model to the study of scenarios has demonstrated the role
      of nutrients and light in the phytoplankton growth, the relationship between DO
      and phytoplankton concentrations, as well as the effect of the BOD degradation in
      the ammonia (NH4) regeneration.

PMID- 15996729
TI  - Accessing gelling ability of vegetable proteins using rheological and
      fluorescence techniques.
AB  - This work aims to present a comprehensive study about the macroscopic
      characteristics of globular vegetable proteins, in terms of their gelling
      ability, by understanding their molecular behaviour, when submitted to a thermal
      gelling process. The gels of soy, pea and lupin proteins were characterized by
      rheological techniques. Gelation kinetics, mechanical spectra, as well as the
      texture of these gels were analyzed and compared. Additionally, capillary
      viscometry, steady-state fluorescence and fluorescence anisotropy were used to
      monitor the structural changes induced by the thermal denaturation, which
      constitutes the main condition for the formation of a gel structure. Based on
      these techniques it was possible to establish a relationship between the gelling
      ability of each protein isolate and their structural resistance to thermal
      unfolding, enabling us to explain the weakest and the strongest gelling ability
      observed for lupin and soy proteins isolates, respectively.

PMID- 15996730
TI  - Two-dimensional patterning of thin coatings for the control of tissue outgrowth.
AB  - Control of the precise location and extent of cellular attachment and
      proliferation, and of tissue outgrowth is important in a number of biomedical
      applications, including biomaterials and tissue engineered medical devices. Here
      we describe a method to control and direct the location and define boundaries of
      tissue growth on surfaces in two dimensions. The method relies on the generation
      of a spatially defined surface chemistry comprising protein adsorbing and non
      adsorbing areas that allow control over the adsorption of cell-adhesive
      glycoproteins. Surface modification was carried out by deposition of thin
      acetaldehyde and allylamine plasma polymer coatings on silicon wafer and FEP
      substrates, followed by grafting of a protein resistant layer of poly(ethylene
      oxide). Spatially controlled patterning of the surface chemistry was achieved by
      masking during plasma polymerization. XPS and AFM were used to provide evidence
      of successful surface modifications. Adsorption of the extracellular matrix
      protein collagen I followed by tissue outgrowth experiments with bovine corneal
      epithelial tissue for up to 21 days showed that two-dimensional control over
      tissue outgrowth is achievable with our patterning method over extended time
      frames. The method promises to be an effective tool for use in a number of in
      vitro and in vivo applications.

PMID- 15996731
TI  - Haunting appearance of bcr/abl fusion gene products in a patient with therapy
      related leukaemia.
AB  - A 81-year-old man was diagnosed as multiple myeloma and had received melphalan
      for 6 years. After that, he developed acute myeloid leukemia (AML) with monosomy
      7 and minor bcr/abl transcripts. Fluorescence in situ hybridization identified no
      detectable level of bcr/abl rearrangement. During chemotherapy for AML, minor
      bcr/abl transcripts disappeared and instead major bcr/abl transcripts emerged. He
      died of pneumonia 3 months later. At that time, neither minor nor major bcr/abl
      transcripts were seen. These observations suggest that certain therapy related
      leukemia may be susceptible to generate very small clones with bcr/abl
      rearrangements.

PMID- 15996732
TI  - Analysis of FLT3 internal tandem duplication and D835 mutations in Chinese acute
      leukemia patients.
AB  - Genomic aberrations of Fms-like tyrosine kinase 3 (FLT3), including internal
      tandem duplication (ITD) and point mutations, have been demonstrated in 25-30% of
      adults acute myeloid leukemia (AML) and are markers of poor prognosis. FLT3/ITD
      and D835 mutations were analyzed in 194 Chinese patients with acute leukemia and
      myelodysplastic syndromes (MDS) by polymerase chain reaction (PCR). FLT3/ITDs and
      D835 mutations were found in 25.9 and 6.3% of 143 AML patients, respectively. Two
      patients showed both ITD and point mutations. Among the FAB subtypes of AML, the
      rate of FLT3 aberration was significantly higher in M3 and M5. However, neither
      aberrations was found in 25 patients with acute lymphoblastic leukemia (ALL), 2
      acute hybrid leukemia, 17 MDS and 7 chronic myeloid leukemia in blast crisis (CML
      BC). FLT3/ITD was associated to leukocytosis and lower complete remission (CR)
      rate, and was more prevalent in patients with normal karyotype. In contrast, D835
      mutation was not associated with leukocytosis or low CR rate. Our results confirm
      that FLT3 activating mutations also occur in a significant percentage in Chinese
      AML patients. FLT3/ITD(+) patients treated with standard induction regimen could
      achieve lower complete remission rates compared with patients not harboring this
      defect. Early detection of FLT3 mutations and an intensification of induction
      therapy might thus be useful for this group of patients to overcome the poor
      prognosis.

PMID- 15996733
TI  - Composition, sources, and potential toxicological significance of PAHs in the
      surface sediments of the Meiliang Bay, Taihu Lake, China.
AB  - Twenty-five surface sediment samples were collected from Meiliang Bay, Taihu
      Lake, China, in 2003. The concentrations of 16 polycyclic aromatic hydrocarbons
      (PAHs), identified as priority pollutants by the USEPA, were determined by gas
      chromatography equipped with a mass spectrometry detector (GC-MS). Total
      concentrations of the PAHs ranged from 1207 to 4754 ng/g dry weight. Sediment
      samples with the highest PAH concentrations were from the northern site of the
      bay, which is in proximity to the incoming PAH source; the PAH levels in the
      southern part were relatively low. The observed PAH levels were higher than those
      in river sediments in China but were lower than those found in sediments of urban
      areas and harbors. According to the observed molecular indices, PAHs originated
      largely from the high-temperature pyrolytic process, whereas the petrogenic
      process was more commonly responsible for PAH contamination in harbors. A good
      correlation existed between the benzo[a]pyrene level and the total PAH
      concentration (r=0.97), making benzo[a]pyrene a potential molecular marker for
      PAH pollution. According to the numerical effect-based sediment quality guideline
      (SQGs) of the United States, the levels of PAHs at most studied sites in Meiliang
      Bay, except some sites in the northern part of the bay, should not exert adverse
      biological effects. In the northern part of the bay, the PAH levels at sites 21
      and 22 exceed the effects range low (ERL) and could thus cause acute biological
      impairments, in comparison with the sediment quality guidelines. The total PAH
      levels were expressed as the B[a]P toxicity equivalents (TEQs(carc)) and compared
      to the contaminated sediments from Guba Pechenga, Barents Sea, Russia.

PMID- 15996734
TI  - Comparison between semiautomated kinetic perimetry and conventional Goldmann
      manual kinetic perimetry in advanced visual field loss.
AB  - PURPOSE: To compare quantitatively visual field (VF) results obtained using a new
      standardized semiautomated kinetic perimetry (SKP) with those obtained by
      conventional Goldmann manual kinetic perimetry (MKP) in patients with advanced VF
      loss. DESIGN: Prospective, single-center, observational comparative case series.
      SUBJECTS AND METHODS: Seventy-seven eligible patients (36 suffering from advanced
      retinal nerve fiber layer loss, 20 with concentric constriction of the VF, and 21
      with hemianopia) were included in the study. One eye of each patient was examined
      on the same day with MKP and SKP. Three isopters, identical in both tests, were
      chosen to assess the extent of the VF loss. To compare the location and size of
      the corresponding isopters obtained with MKP and SKP, intersection areas of
      superimposed isopters were expressed as a percentage of union areas. MAIN OUTCOME
      MEASURES: The area and position of isopters for a defined stimulus condition
      obtained with both methods were compared. Test duration and patients' preference
      were also evaluated. RESULTS: Isopters obtained with Goldmann MKP enclosed areas
      smaller by 20% (confidence interval [CI], 12%-27%). The mean intersection area of
      Goldmann and SKP VFs was 1763.1 square degrees (CI, 1558.6-1967.7) smaller than
      the union for stimulus III4e over all groups of patients. Semiautomated kinetic
      perimetry was preferred by 60% of patients with concentric constriction of the
      VF. Median duration of the examination was 15 minutes and did not differ
      significantly between the 2 methods. CONCLUSIONS: Our results indicate that SKP
      isopter shape and size were very comparable to those obtained on the same eyes
      with MKP. Semiautomated kinetic perimetry may represent a more standardized
      method of kinetic perimetry, which still takes advantage of perimetrist-patient
      interaction to diagnose and monitor advanced VF loss in clinical practice.

PMID- 15996735
TI  - Pulsatile blood flow in the polypoidal choroidal vasculopathy.
AB  - OBJECTIVE: To describe patients with pulsatile polypoidal vessels in polypoidal
      choroidal vasculopathy (PCV). DESIGN: Retrospective, observational case series.
      PARTICIPANTS: Eighty-four eyes of 74 patients with PCV. METHODS: The medical
      records of patients diagnosed with PCV between 1998 and 2004 at Kagoshima
      University Hospital were reviewed. MAIN OUTCOME MEASURES: A pulsatile polypoidal
      vessel (PV) on indocyanine green angiography (ICGA). RESULTS: Seven of 74
      patients (9.5%) had PVs in the macula. Four eyes revealed pulsatile PVs on the
      day the diagnosis of PCV was first made, and PVs in the other 3 eyes showed
      pulsatile movement during the follow-up period. Two patterns of pulsatile
      movement were observed on ICGA: (1) a rhythmic variation in the caliber of a
      choroidal vessel (caliber variation pattern) and (2) a pulsatile blood flow in a
      tortuous and relatively narrow choroidal vessel (pulsatile blood flow pattern).
      Both patterns of pulsatile PVs appeared in the early frames of the ICGA, and some
      of them were observable even during the first 15 minutes after the ICG dye
      injection. The pulsatile movement disappeared spontaneously without treatment in
      some patients, and the period in which pulsatile PVs was detectable on ICGA was
      limited in each patient. CONCLUSIONS: We report the features of pulsatile PV in
      PCV. It is a unique and important characteristic that has not been reported with
      any other chorioretinal diseases and may provide a clue to understanding the
      pathogenesis of PCV.

PMID- 15996736
TI  - Enriched but not depleted uranium affects central nervous system in long-term
      exposed rat.
AB  - Uranium is well known to induce chemical toxicity in kidneys, but several other
      target organs, such as central nervous system, could be also affected. Thus in
      the present study, the effects on sleep-wake cycle and behavior were studied
      after chronic oral exposure to enriched or depleted uranium. Rats exposed to 4%
      enriched uranium for 1.5 months through drinking water, accumulated twice as much
      uranium in some key areas such as the hippocampus, hypothalamus and adrenals than
      did control rats. This accumulation was correlated with an increase of about 38%
      of the amount of paradoxical sleep, a reduction of their spatial working memory
      capacities and an increase in their anxiety. Exposure to depleted uranium for 1.5
      months did not induce these effects, suggesting that the radiological activity
      induces the primary events of these effects of uranium.

PMID- 15996737
TI  - Anemia in the recent reported cases of bird flu infection in Thailand and
      Vietnam.

PMID- 15996738
TI  - Three cases of anicteric leptospirosis from Turkey: mild to severe complications.
AB  - Leptospirosis is an acute generalized infectious disease, caused by spirochaetes,
      Leptospira interrogans. The severity of the disease ranges from an asymptomatic
      subclinical course to a fatal outcome. The three cases presented here were
      diagnosed serologically and had thrombocytopenia and acute renal failure as
      complication of anicteric leptospirosis. Our first case admitted with clinical
      presentation of pneumonia but clinical progress and laboratory findings made us
      to consider leptospirosis. The other two cases presented with aseptic meningitis
      were diagnosed as anicteric leptospirosis by the serological test results. One of
      the cases had fatal outcome but could not be strictly correlated with
      leptospirosis.

PMID- 15996739
TI  - Multidrug-resistant tuberculous spondylodiscitis: need for aggressive management
      and drug susceptibility testing of Mycobacterium tuberculosis isolates.
AB  - A 49-year-old woman complaining of thoracic spine pain for 18 months was admitted
      to the hospital for evaluation. Magnetic resonance imaging of the thoracic spine
      showed spondylodiscitis of the T8-T9 intervertebral disk. Computed tomography
      scan-guided fine needle aspiration of the affected area was performed but it did
      not reveal the cause of the disease. Because of continuing symptoms and lack of
      diagnosis the patient underwent a vertebrectomy and substitution of the eighth
      thoracic vertebra with Moss titanium cylinder filled-up with auto-bone grafts.
      Culture of the extracted bone grew Mycobacterium tuberculosis, which was
      resistant to isoniazid and rifampin. Persistent and even invasive diagnostic work
      up is needed for the proper and prompt management of patients with
      spondylodiscitis.

PMID- 15996740
TI  - Pulmonary nocardiosis in a patient with idiopathic thrombocytopenic purpura.
AB  - We present a case of pulmonary nocardiosis in a patient suffering from idiopathic
      thrombocytopenic purpura (ITP), an autoimmune disorder in which platelets are
      immunologically destroyed. ITP corticosteroid therapy, as well as the patient's
      diabetes mellitus history caused immunosuppression, leading to an incidental lung
      infection by nocardia asteroides. The combination of pulmonary nocardiosis and
      ITP is, as far as we know, very rare.

PMID- 15996741
TI  - Trimethoprim-sulfamethoxazole induced rash and fatal hematologic disorders.
AB  - Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination chemotherapeutic agent,
      a commonly used antibiotic. Adverse drug reactions occur in 6-8% of patients.
      Although, the most common adverse reactions include mild gastrointestinal
      distress and cutaneous events, also a wide range of hematological abnormalities
      have been ascribed to TMP-SMX. We report a 40-year-old male patient who developed
      an early onset neutropenia, thrombocytopenia, generalised rash and oral
      candidiasis after 5 days long TMP-SMX therapy. Although generalised rash may seen
      more and improves with discontinuation of the therapy; severe neutropenia,
      thrombocytopenia and oral candidiasis are seen very rare and rarely leads to
      fatality as it was in our case. Despite thrombocyte transfusions, whole blood
      transfusions, red cell concentrates and filgrastim therapy we lost our patient.
      We want to underline that although the TMP-SMX combination is usually well
      tolerated it can also lead to fatal complications.

PMID- 15996742
TI  - Severe watery diarrhoea and bacteraemia caused by Vibrio fluvialis.
AB  - Individual cases and outbreaks of Vibrio fluvialis-associated gastroenteritis
      have been reported sporadically, with just one fatal bacteraemia case complicated
      with shigellosis described. We present a patient that suffered from severe watery
      diarrhoea requiring parenteral hyperalimentation. V. fluvialis simultaneously
      cultured from stool and blood proved to be the same strain by random amplified
      polymorphic DNA (RAPD) analysis. The patient was cured with intravenous
      administration of antibiotics and supportive treatment. To the best of our
      knowledge, this is the first case of gastroenteritis and bacteraemia caused by V.
      fluvialis.

PMID- 15996743
TI  - Severe efavirenz-induced hypersensitivity syndrome (not-DRESS) with acute renal
      failure.
AB  - We report on a Subsaharian patient with HIV infection and disseminated
      tuberculosis who developed acute, severe hypersensitivity reaction to efavirenz
      including acute renal failure in addition to liver and lung involvement, in the
      absence of skin changes or blood eosinophilia.

PMID- 15996744
TI  - In vitro activity of telithromycin against Gram-negative bacterial pathogens.
AB  - OBJECTIVES: To investigate the in vitro activity of the ketolide anti-bacterial
      telithromycin against a range of commensal bacteria and common aerobic Gram
      negative respiratory and non-respiratory pathogens. METHODS: Isolates were
      derived from both clinical material supplied by centres in various European
      countries and patients with community-acquired respiratory tract infections
      (RTIs) from centres worldwide as part of a longitudinal surveillance study.
      Telithromycin susceptibility testing was conducted using methods in accordance
      with Clinical and Laboratory Standards Institute (CLSI) guidelines and
      interpreted using CLSI breakpoints. RESULTS: Telithromycin displayed the highest
      activity against clinical isolates of Haemophilus spp., Neisseria spp.,
      Bordetella pertussis, Legionella pneumophila and Moraxella catarrhalis, with low
      activity against a number of other bacterial species, including Acinetobacter
      spp., Enterobacteriaceae spp., Vibrio spp., Campylobacter jejuni, Aeromonas
      hydrophila, Plesiomonas shigelloides and Pseudomonas aeruginosa. CONCLUSIONS:
      Telithromycin provides coverage of key Gram-negative respiratory tract pathogens,
      but has minimal activity against Gram-negative non-respiratory pathogens and
      commensal bacteria. These data support the use of telithromycin as an alternative
      empirical therapy for community-acquired RTIs.

PMID- 15996745
TI  - L. micdadei PVE successfully treated with levofloxacin/valve replacement: case
      report and review of the literature.
AB  - Prosthetic valve endocarditis (PVE) due to Legionella micdadei was diagnosed in a
      man a year after valve replacement with a bovine xenograft. He did not have
      pneumonia. The microbiologic diagnosis was established after valvectomy, which
      was necessitated by failure of empiric antibiotics to eradicate the infection.
      The fastidious organism grew only on buffered charcoal yeast extract agar and was
      confirmed as L. micdadei by gene sequence analysis. We believe this to be the
      first culture-proven case of L. micdadei PVE reported in the literature.

PMID- 15996746
TI  - GABA(A) receptor subtypes as targets for neuropsychiatric drug development.
AB  - The main inhibitory neurotransmitter system in the brain, the gamma-aminobutyric
      acid (GABA) system, is the target for many clinically used drugs to treat, for
      example, anxiety disorders and epilepsy and to induce sedation and anesthesia.
      These drugs facilitate the function of pentameric A-type GABA (GABA(A)) receptors
      that are extremely widespread in the brain and composed from the repertoire of 19
      subunit variants. Modern genetic studies have found associations of various
      subunit gene polymorphisms with neuropsychiatric disorders, including alcoholism,
      schizophrenia, anxiety, and bipolar affective disorder, but these studies are
      still at their early phase because they still have failed to lead to validated
      drug development targets. Recent neurobiological studies on new animal models and
      receptor subunit mutations have revealed novel aspects of the GABA(A) receptors,
      which might allow selective targeting of the drug action in receptor subtype
      selective fashion, either on the synaptic or extrasynaptic receptor populations.
      More precisely, the greatest advances have occurred in the clarification of the
      molecular and behavioral mechanisms of action of the GABA(A) receptor agonists
      already in the clinical use, such as benzodiazepines and anesthetics, rather than
      in the introduction of novel compounds to clinical practice. It is likely that
      these new developments will help to overcome the present problems of the chronic
      treatment with nonselective GABA(A) agonists, that is, the development of
      tolerance and dependence, and to focus the drug action on the neurobiologically
      and neuropathologically relevant substrates.

PMID- 15996747
TI  - Postpartum disorders: multiple interacting underlying mechanisms and risk
      factors.

PMID- 15996748
TI  - Correlates of trait impulsiveness in performance measures and neuropsychological
      tests.
AB  - Performance measures of impulsiveness offer great promise for assessing this
      trait in clinical and experimental studies. However, little is known about their
      relative superiority or inferiority to standard cognitive performance measures as
      correlates of this trait. In this study, 58 healthy volunteers completed a self
      rating of impulsiveness (Barratt Impulsiveness Scale) and a battery of
      neuropsychological tests. The test battery included measures of reaction time,
      attention, memory, fluency, and executive function, as well as two performance
      measures of impulsiveness--Time Estimation and a Go-No Go task. Self-ratings
      correlated moderately with a number of these test scores, but many correlations
      became non-significant after adjustment for age and education. Correlations with
      the Go-No Go task, verbal fluency, executive function measures (Trails B), and
      tasks requiring decision-making against time (Choice Reaction Time, Reaction Time
      to Paired Words and Paired Faces Memory Tasks, and response bias on the
      Continuous Performance Test) remained significant. Performance on the Go-No Go
      task was the strongest correlate of self-rated impulsiveness. The findings
      suggest that once general demographic or ability factors are accounted for,
      specialized performance tasks requiring decision-making and response organization
      under time pressure provide the most effective means of assessing this behavioral
      trait.

PMID- 15996749
TI  - Gradations of clinical severity and sensitivity to change assessed with the Beck
      Depression Inventory-II in Japanese patients with depression.
AB  - Knowledge of what constitutes a minimal clinically important difference and
      change on a psychiatric rating scale is essential in interpreting its scores. The
      present study examines the Beck Depression Inventory-II (BDI-II), a recently
      revised successor to the world's most popular self-rating instrument for
      depression. BDI-II was administered to 85 patients with major depression,
      diagnosed with DSM-IV along with its severity specifiers. It was again
      administered to 40 first-visit patients from the original sample when they
      returned 14 or more days later. The Clinical Global Impression-Change Scale was
      rated at the same time. All the ratings were done independent of each other. The
      BDI-II was able to distinguish between all grades of depression severity. An
      approximate 10-point difference existed between each severity specifier. The BDI
      II was also sensitive to change in depression: a 5-point difference corresponded
      to a minimally important clinical difference, 10-19 points to a moderate
      difference, and 20 or more points to a large difference. Given the already
      established high reliability, content validity, construct validity and factorial
      validity, and the high sensitivity to between-subject differences and within
      subject changes demonstrated in the present study, the BDI-II promises to
      continue to be a leading self-rating instrument to assess depression severity
      worldwide.

PMID- 15996750
TI  - No association between common variations in the neuronal nicotinic acetylcholine
      receptor alpha2 subunit gene (CHRNA2) and bipolar I disorder.
AB  - The neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) maps
      to the bipolar susceptibility locus on chromosome 8p21-22. Given the biological
      role of the neuronal nicotinic acetylcholine receptors and the substantial
      comorbidity of nicotine dependence in psychiatric disorders, the CHRNA2 gene is a
      plausible candidate gene for bipolar disorder (BPD). We tested the hypothesis
      that variations in the CHRNA2 gene confer susceptibility to bipolar I disorder in
      a case-control association study. Genotypes of one amino acid substitution
      polymorphism (Ala125Thr) and five non-coding variations across the CHRNA2 gene
      were obtained from 345 unrelated bipolar I patients and 273 control samples.
      Genotypes and allele frequencies were compared between groups using chi-square
      contingency analysis. Linkage disequilibrium (LD) between markers was calculated,
      and estimated haplotype frequencies were compared between groups. We observed no
      statitistically significant difference in genotype and allele frequencies for all
      six variations between bipolar patients and controls, but we did demonstrate
      strong LD throughout the gene. Haplotype analysis showed that no combinations of
      alleles were associated with illness. Our results suggest that common variations
      in the CHRNA2 gene are unlikely to confer susceptibility to BPD in this sample.
      Further studies are required to elucidate the susceptibility locus for BPD on
      chromosome 8p21-22.

PMID- 15996751
TI  - A rating scale for neuroleptic malignant syndrome.
AB  - The development of a rating scale for neuroleptic malignant syndrome (NMS) is
      described. The clinical and laboratory features of NMS were categorised into six
      domains after a thorough literature review and examination of patients. The
      reliability of this scale was established on 25 NMS patients and 50 control
      subjects based on chart reviews. A factor analysis supported a six-factor
      solution. The validity of the scale was indicated by the relationship of the
      severity rating to duration of illness and outcome. The inter-rater reliability
      of the scale was established prospectively in 10 subjects. The scale offers a
      measure of severity of NMS in the clinical setting so as to support the clinical
      diagnosis, monitor patients and determine their progress. The scale may be
      applicable not only to NMS or suspected NMS but also to NMS-like syndromes such
      as lethal catatonia.

PMID- 15996752
TI  - Plasma concentrations of anxiolytic neuroactive steroids in men with panic
      disorder.
AB  - Plasma concentrations of neuroactive steroids in men with panic disorder (PD)
      were measured to evaluate their relations to psychopathology both before and
      during treatment. Participants comprised 13 men with PD and 10 normal controls.
      Patients were evaluated while drug-free as well as after 1 and 2 months of
      paroxetine therapy. Psychopathology was assessed by the State-Trait Anxiety
      Inventory (STAI), the Panic-Associated Symptom Scale, and the Fear Questionnaire
      total score. Plasma concentrations of steroids were measured by radioimmunoassay.
      The plasma concentrations of progesterone and dehydroepiandrosterone were greater
      in drug-free patients than in controls, whereas those of allopregnanolone and
      tetrahydrodeoxycorticosterone did not differ between the two groups. Paroxetine
      treatment for 2 months significantly increased the plasma concentration of
      allopregnanolone but did not affect those of the other steroids. At 2 months of
      therapy, allopregnanolone concentrations in patients were significantly greater
      than those in controls. The plasma concentrations of progesterone and
      tetrahydrodeoxycorticosterone correlated with the STAI state score in patients
      before treatment. Our data suggest that neuroactive steroids may play a role in
      PD in men.

PMID- 15996753
TI  - Empirical evidence for an invariant three-factor structure of the Parental
      Bonding Instrument in six European countries.
AB  - The objective of the present study was to test the Parental Bonding Instrument's
      (PBI) three-factor structure (care, overprotection, and authoritarianism) found
      by [Cox, B.J., Enns, M.W., Clara, I.P. 2000, The Parental Bonding Instrument:
      confirmatory evidence for a three-factor model in a psychiatric clinical sample
      and in the National Comorbidity Survey, Social Psychiatry and Psychiatric
      Epidemiology 35 (2000) 353-357.] on an eight-item short form of the scale. A
      total of 8813 respondents from the six European countries participating in the
      ESEMeD project (Belgium, France, Germany, Italy, The Netherlands, and Spain)
      completed either the PBI-paternal or the PBI-maternal scale. Maximum likelihood
      confirmatory factor analysis was used to compare the original factor model of Cox
      et al. with a three-factor solution that emerged from an exploration of the
      structure with principal component factor analysis. When gender and age
      subgroups, as well as different countries, were taken into account, the accuracy
      of the model was confirmed. The fit indices for the new model indicated a
      generally better model fit than the ones for the model originally developed by
      Cox et al. Further efforts should be directed to the modeling of the dimension
      authoritarianism. The results provide the opportunity to estimate the influence
      of the extracted factors on mental disorders in different countries. The
      application of the short form of the PBI seems suitable primarily for large
      epidemiological studies.

PMID- 15996754
TI  - Differential expression and secretion of bovine serum amyloid A3 (SAA3) by
      mammary epithelial cells stimulated with prolactin or lipopolysaccharide.
AB  - Serum amyloid A (SAA) proteins were originally identified as prominent acute
      phase serum reactants synthesized predominately by hepatocytes in response to
      infection, inflammation and trauma. In this study, we report the differential
      expression and secretion of serum amyloid A3 (SAA3) by bovine mammary epithelial
      cells following stimulation with either prolactin (PRL) or lipopolysaccharide
      (LPS). Reverse transcription-polymerase chain reaction analysis of PRL or LPS
      induced bovine mammary epithelial cells resulted in the detection of only the
      mammary-derived Saa3 (M-Saa3) transcript. Two-dimensional immunoblot analyses of
      colostrum and milk from healthy cows, as well as conditioned medium from PRL or
      LPS stimulated bovine mammary epithelial cells confirmed the differential
      production and secretion of M-SAA3 while other SAA isoforms were not detected.
      These data indicate that the bovine Saa3 gene is regulated differently from the
      other Saa genes with regard to the site of and stimulus for expression,
      suggesting an important tissue-specific function for bovine M-SAA3 during
      lactation and mammary infection.

PMID- 15996755
TI  - Inhibition of transmethylation disturbs neurulation in chick embryos.
AB  - Periconceptional folic acid supplementation can reduce the occurrence of neural
      tube defects. A low folate status will result in reduced remethylation of
      homocysteine (Hcy) to methionine and, subsequently, in a rise of Hcy levels.
      Indeed, elevated Hcy concentrations have been reported in mothers of children
      with neural tube defects. In our previous study, we showed that treatment of
      chick embryos with Hcy resulted in a delay of neural tube closure in an in vitro
      model. In the present study, we examined whether this effect of Hcy is due to
      inhibition of transmethylation via elevation of S-adenosylhomocysteine (AdoHcy).
      Transmethylation involves methylation of DNA, RNA and proteins by donation of a
      methyl group from S-adenosylmethionine (AdoMet). After application of inhibitors
      of S-adenosylhomocysteine hydrolase and of methionine adenosyltransferase, a
      delay of anterior neuropore closure, comparable to that observed after Hcy
      treatment, was observed. The changes in AdoMet and AdoHcy concentrations
      confirmed the inhibition of S-adenosylhomocysteine hydrolase or methionine
      adenosyltransferase, respectively, and the AdoMet/AdoHcy ratio was decreased in
      all cases, indicating reduced transmethylation. Moreover, the inhibition of
      methionine adenosyltransferase was prevented by pretreatment with methionine.
      This study, therefore, indicates that the Hcy-induced delay of the neural tube
      closure is caused by the inhibition of transmethylation via elevation of AdoHcy
      levels and a reduction of the AdoMet/AdoHcy ratio.

PMID- 15996756
TI  - Nucleotide variation analysis does not support a causal role for plexin-A1 in
      hereditary congenital facial paresis.
AB  - Hereditary congenital facial paresis is a rare autosomal dominantly inherited
      disorder, in which pathological changes in the brainstem affect the paired facial
      nuclei and nerves. Previously, the neuropilin-1 protein has been shown to control
      axon guidance and cell body position of facial motor neurons, and mice with a
      targeted disruption of neuropilin-1 present with developmental defects of the
      facial nerve nuclei. Plexin-A1 can function as a signal transducing subunit for
      the neuronal neuropilin receptor, and its gene is located in the linkage interval
      for hereditary congenital facial paresis at chromosome 3q21-q22 (MIM601471),
      making it an excellent candidate gene for this disorder. During mouse
      embryogenesis, the murine ortholog of plexin-A1 gene showed restricted spatial
      and temporal expression in the hindbrain, consistent with a role in cell body
      movement, or axonal guidance during facial nerve development. Sequence analysis
      of the plexin-A1 gene in patients from the 3q21-q22-linked hereditary congenital
      facial paresis family revealed several nucleotide changes. However, none of the
      nucleotide changes led to an amino acid substitution, and reverse transcriptase
      polymerase chain reaction analysis did not detect aberrant RNA processing. We
      therefore conclude that it is highly unlikely that Plexin-A1 is involved in the
      pathogenicity of hereditary congenital facial paresis.

PMID- 15996757
TI  - Effect of endogenous catecholamines in lymphocytes on lymphocyte function.
AB  - Our previous work has showed that lymphocytes can synthesize catecholamines
      (CAs). However, role and mechanism of the endogenous CAs in lymphocytes in
      modulation of immune function are less known. In the present study, we used alpha
      methyl-p-tyrosine (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), and
      pargyline, an inhibitor of monoamine oxydase, to block the synthesis and
      degradation of CAs in lymphocytes and then observed changes of lymphocyte
      proliferation induced by concanavalin A (Con A). Phentolamine and propranolol,
      antagonists respectively to alpha- and beta-adrenoreceptors, were employed to
      investigate the receptor mechanism. We found that TH mRNA in the Con A-activated
      lymphocytes was 2.4 times higher in relative density than that in the resting
      lymphocytes. Similarly, the intracellular and supernatant CAs, including DA, NE
      and E, of the Con A-stimulated lymphocytes were significantly raised relative to
      those of the resting cells. alpha-MT (10(-11), 10(-10) and 10(-9) M) facilitated
      the Con A-induced lymphocyte proliferation, but pargyline (10(-11), 10(-10) and
      10(-9) M) attenuated the cell proliferation. Meanwhile, alpha-MT and pargyline
      respectively led to decrease and increase in the intracellular and supernatant
      CAs (DA, NE and E) of the Con A-stimulated lymphocytes. Propranolol completely
      blocked, but phentolamine partly reversed, the suppressive effect of pargyline on
      the Con A-induced lymphocyte proliferation. Content of cAMP was remarkably
      increased in the lymphocytes treated with pargyline alone, but it dropped to
      control level after these cells were treated with propranolol plus pargyline.
      These results on the one hand further demonstrate the ability of lymphocytes to
      synthesize CAs and the enhancive ability of the activated lymphocytes to
      synthesize CAs, and on the other hand reveal an important role of the endogenous
      CAs in regulation of function of lymphocytes themselves. Besides, our present
      findings suggest that CAs synthesized by lymphocytes can secrete out of the
      lymphocytes via paracrine or autocrine pathway and affect lymphocyte function by
      beta-adrenoreceptor and cAMP mediating mechanism. Thus, it can be implied that
      CAs in lymphocytes are also involved in the cross-talk in the neuro-endocrine
      immune networks.

PMID- 15996759
TI  - Prognostic factors of pediatric endoscopic sinus surgery.
AB  - OBJECTIVE: Pediatric endoscopic sinus surgery (ESS) is performed for refractory
      cases of rhinosinusitis that do not respond to medical management. However, few
      studies have been reported for the prognostic factors affecting the outcomes of
      pediatric ESS. The aim of this study was to investigate the prognostic factors
      affecting the outcomes of pediatric ESS. MATERIALS AND METHOD: Medical records of
      97 pediatric patients who had undergone ESS from February 1995 to October 2003
      were reviewed retrospectively. We classified the patients into two groups based
      on outcome, i.e., either good or poor, according to the postoperative endoscopic
      findings. Then univariate and multivariate analyses were performed to compare the
      following nine characteristics between the good and poor outcome groups: the
      presence of allergy, bronchial asthma, adenotonsillar hypertrophy, history of
      previous sinus surgery, presence of a smoker in the family, degree of polyposis,
      preoperative disease extent scored by CT scan findings, blood eosinophil count,
      and eosinophil infiltration in the nasal mucosa. RESULT: The overall success rate
      was 70% based on the objective postoperative endoscopic finding. Statistical
      differences were found between the good and poor groups in terms of the degree of
      preoperative polyposis and CT staging in univariate analysis, whilst in
      multivariate logistic regression analysis severe polyposis and indirect smoking
      predicted poor outcome after pediatric ESS. CONCLUSION: Pediatric ESS with severe
      polyposis, high CT rhinosinusitis staging, or indirect smoking predisposes to a
      poorer outcome. This needs to be taken into consideration when performing ESS for
      children.

PMID- 15996758
TI  - The effects of repeated endotoxin exposure on rat brain metabolites as measured
      by ex vivo 1HMRS.
AB  - Abnormalities in brain chemistry induced by acute or chronic treatment with LPS
      were studied in the rat model. Ex vivo brain metabolites were measured using
      proton magnetic resonance spectroscopy, whereas serum corticosterone levels were
      determined using radioimmunoassay. We observed increased lactate levels in all
      measured brain regions and decreased choline in the hypothalamus after chronic
      LPS treatment. Acute LPS treatment led to an elevation of corticosterone, whereas
      chronic LPS treatment led to attenuation of the HPA response. These findings
      suggest that chronic inflammation induced by LPS could lead to cell
      loss/dysfunction, and hence, desensitization of the HPA axis, particularly in the
      hypothalamus.

PMID- 15996761
TI  - Adenomatoid odontogenic tumor mimicking a dentigerous cyst.
AB  - Adenomatoid odontogenic tumor (AOT) is a slow-growing, asymptomatic and uncommon
      lesion that arises from odontogenic epithelium with inductive effects on
      connective tissue. The more common variant is the follicular type, which involves
      an unerupted tooth and is often mistaken for a dentigerous cyst. Histopathologic
      examination demonstrates cuboidal or spindle-shaped epithelial cells forming
      aggregates or rosette-like structures with minimal connective tissue, and
      cuboidal or low columnar cells forming glandular duct-like structures. Treatment
      is complete enucleation, and recurrences are rare. We presented a case of AOT in
      a 14-year-old male presenting as a cystic mass around an unerupted tooth.

PMID- 15996760
TI  - Gastroesophageal reflux disease: its importance in ear, nose, and throat
      practice.
AB  - OBJECTIVE: Gastroesophageal reflux disease (GERD) has been implicated in various
      extra-gastroesophageal diseases, especially in the upper and lower airways
      (atypical GERD). The objective of the present study was to determine the
      frequency of gastroesophageal and extra-gastroesophageal symptoms in pediatric
      patients with GERD and their response to the general treatment. MATERIAL AND
      METHODS: A retrospective study was conducted on 45 children of both sexes aged 3
      months-12 years with GERD diagnosed by clinical examination and 24h single
      channel pHmetry. The gastroesophageal and extra-gastroesophageal symptoms, the
      treatment instituted and the response of the patients to the latter were
      determined. RESULTS: Five symptomatologic groups were identified:
      gastroesophageal (51.11%), pulmonary (recurrent pneumonia, 40%, and bronchial
      asthma, 46.67%), chronic cough (64.44%), rhinologic (chronic nasal obstruction,
      68.88%, nasal secretion, 55.55%, and nose itching, 46.66%), and pharyngo-otologic
      (recurrent acute middle ear infection, 35.56%, and recurrent tonsillitis,
      24.44%). The response to treatment (antireflux drugs, antiallergic drugs, and
      surgical procedures) resulted in cure in 24 patients (53.34%), while 21 continued
      to be symptomatic. The cure rate was 69.56% for the gastroesophageal group, 100%
      for the recurrent pneumonia group, 80.95% for the bronchial asthma group, 68.96%
      for the chronic cough group, 83.87% for the chronic nasal obstruction group, 80%
      for the nasal secretion group, 85.71% for the nose itching group, 100% for the
      recurrent acute middle ear infection group, and 90.90% for the recurrent
      tonsillitis group. Total treatment time was 1.8 times longer for the remission of
      extra-gastroesophageal symptoms. Exclusive antireflux treatment promoted full
      remission of the otorhinolaryngologic symptoms in 38.89% of patients (nasal
      41.17%, recurrent acute middle ear infection-12.5%, and recurrent tonsillitis
      18.18%). CONCLUSION: GERD can cause otorhinolaryngologic symptoms in children and
      remission of these symptoms can be obtained with antireflux therapy.

PMID- 15996762
TI  - Association between adenoidal-nasopharyngeal ratio and right ventricular
      diastolic functions in children with adenoid hypertrophy causing upper airway
      obstruction.
AB  - OBJECTIVE: Adenoid hypertrophy causing upper airway obstruction can cause
      cardiovascular complications, including pulmonary hypertension and right heart
      failure in children. Adenoidal-nasopharyngeal ratio (ANR) is a practical, non
      invasive and reliable method to evaluate adenoid enlargement. Our aim was to
      evaluate a possible association between ANR and echocardiographic parameters of
      right ventricle. METHODS: Twenty-one children who were affected by upper
      respiratory obstruction symptoms due to adenoid hypertrophy were included in this
      study (male/female: 12/9; mean age was 6.0 +/- 1.5 years). ANRs were calculated
      as the ratio of adenoidal depths to the nasopharyngeal depths on lateral
      cephalometric radiographs. Pulmonary arterial pressures, right ventricular
      diastolic filling parameters (peak E, peak A, E/A ratio), right ventricular end
      diastolic diameters, and left ventricular ejection fractions were measured using
      echocardiography both preoperatively and also 3 months after the operation.
      RESULTS: Preoperative pulmonary arterial pressure, E/A ratio, right ventricular
      end-diastolic diameter, and left ventricular ejection fraction values were 23.10
      +/-3.43 mmHg, 1.01 +/- 0.20, 1.95 +/- 0.16 cm, and 69.43 +/- 3.68%, respectively.
      Postoperative pulmonary arterial pressure, E/A ratio, right ventricular end
      diastolic diameter, and left ventricular ejection fraction values were 16.94 +/-
      1.45 mmHg, 1.24 +/- 0.14, 1.72 +/- 0.15 cm, and 69.77 +/- 2.17%, respectively.
      There were significant differences between preoperative and postoperative
      pulmonary arterial pressures, E/A ratios, and right ventricular end-diastolic
      diameters (p < 0.01 for each), while left ventricular ejection fraction values
      did not significantly change after the operation (p > 0.05). There was a negative
      correlation between E/A ratio and ANR-Ba (p < 0.05, r = -0.44). CONCLUSION: ANR
      can give information about the right ventricular functions in children with
      enlarged adenoids causing obstructive symptoms.

PMID- 15996763
TI  - An improved reverse transcription-polymerase chain reaction (RT-PCR) assay for
      the detection of two cherry flexiviruses in Prunus spp.
AB  - A one-step reverse transcription-polymerase chain reaction (RT-PCR) procedure was
      developed to detect Cherry green ring mottle virus (CGRMV) and Cherry necrotic
      rusty mottle virus (CNRMV) in woody indicators and naturally infected Prunus spp.
      Viral RNA suitable for RT-PCR was obtained by a simple trapping method that did
      not require either extraction of double-stranded RNA (dsRNA) or total RNA,
      availability of virus antibodies, or purification of viral particles. Consensus
      primers, degenerate primers and virus-specific primers, whose designs were based
      on alignments of available cherry flexivirus sequences, were tested to amplify
      viral genomic fragments of six CGRMV isolates and one CNRMV isolate. RT-PCR
      allowed CGRMV detection in total RNA and viral RNA preparations equivalent to
      400mug and 4mug of infected leaf tissue, respectively. CGRMV was detected in
      tender shoots, leaves, bark and root tips, and the strongest bands were obtained
      using young leaves. Detection was less consistent in summer when the temperature
      was elevated and plant tissues were old. A direct comparison of the RT-PCR and
      grafting assays indicated that the RT-PCR assay is sensitive, rapid and reliable.
      The method will improve the routine diagnosis of cherry flexiviruses in Prunus
      spp.

PMID- 15996764
TI  - Rapid and sensitive HBsAg immunoassay based on fluorescent nanoparticle labels
      and time-resolved detection.
AB  - The detection of hepatitis B virus in blood specimens is carried out commonly by
      measuring surface antigen (HBsAg) levels with assays designed for various random
      access immunoanalysers or rapid near-patient testing. These methods leave much to
      be desired in performance or throughput. The aim of this study was to develop a
      nanoparticle label-based rapid and sensitive HBsAg immunoassay and evaluate its
      performance compared to a well-established reference immunoassay (Enzygnost HBsAg
      5.0). The assay developed is based on kinetic format and relies on one-step two
      site antibody-antigen interaction. Europium(III)-chelate-doped nanoparticles and
      microtiter wells were coated with anti-HBsAg monoclonal antibodies specific for
      discrete epitopes. The adaptation of nanoparticle labels for quantitative HBsAg
      detection showed improved sensitivity (LLD: 0.028 ng/ml) and dynamics (up to 1000
      ng/ml) with reasonably low coefficients of variation (concentration-CV%s 2.8
      21.9%). Furthermore, concurrent sample runs with the ELISA reference method
      showed 100% agreement. The time required for the assay was only 10 min
      facilitating a rapid and convenient method for hepatitis B screening.

PMID- 15996765
TI  - SNARE complexes prepare for membrane fusion.
AB  - According to a popular theory, the three presynaptic SNARE proteins (syntaxin 1,
      synaptobrevin 2 and SNAP-25) drive neuroexocytosis by forming a complex that
      forces vesicle and plasma membranes together. However, individual reactions in
      this process have been difficult to resolve. Now, two groups have succeeded in
      studying a very early and a very late step in the fusion process.

PMID- 15996766
TI  - An unusual surface peroxiredoxin protects invasive Entamoeba histolytica from
      oxidant attack.
AB  - Peroxiredoxins are an important class of antioxidant enzymes found from Archaea
      to humans, which reduce and thereby detoxify peroxides and peroxynitrites. The
      major thiol-containing surface antigen of the invasive ameba, Entamoeba
      histolytica, is a peroxiredoxin and is likely to be important during the
      transition from the anaerobic environment of the large intestine to human
      tissues. The closely related species, Entamoeba dispar, is incapable of invasion
      and more sensitive to hydrogen peroxide, yet also has a peroxiredoxin. We cloned
      and expressed the two active recombinant enzymes and found that their activity
      was similar by a fluorometric stopped-flow assay, giving a Km of <10 microM for
      hydrogen peroxide. Three monoclonal antibodies produced to recombinant E.
      histolytica peroxiredoxin cross-reacted with Entamoeba dispar.E. histolytica
      contains as much as 50 times more peroxiredoxin than E. dispar as demonstrated by
      a sensitive capture ELISA. In addition, the peroxiredoxin is present largely on
      the outer surface of the cell, in contrast to E. dispar. This unusual
      peroxiredoxin localizes to the site of parasite-host cell contact where it can
      effectively counteract oxidants generated by host cells, thus facilitating
      invasion.

PMID- 15996767
TI  - Identification of a subtelomeric gene family expressed during the asexual-sexual
      stage transition in Plasmodium falciparum.
AB  - For malaria transmission, the parasite must undergo sexual differentiation into
      mature gametocytes. However, the molecular basis for this critical transition in
      the parasites life cycle is unknown. Six previously uncharacterized genes,
      Pfg14.744, Pfg14.745, Pfg14.748, Pfg14.763, Pfg14.752 and Pfg6.6 that are members
      of a 36 gene Plasmodium falciparum-specific subtelomeric superfamily were found
      to be expressed in parasites that are committed to sexual development as
      suggested by co-expression of Pfs16 and Pfg27. Northern blots demonstrated that
      Pfg14.744 and Pfg14.748 were first expressed before the parasites differentiated
      into morphologically distinct gametocytes, transcription continued to increase
      until stage II gametocytes were formed and then rapidly decreased.
      Immunofluorescence assays indicated that both proteins were only produced in the
      subpopulation of ring stage parasites that are committed to gametocytogenesis and
      both localized to the parasitophorous vacuole (PV)b of the early ring stage
      parasites. As the parasites continued to develop Pfg14.748 remained within the
      parasitophorous vacuole, while Pfg14.744 was detected in the erythrocyte. The 5'
      flanking region of either gene alone was sufficient to drive early gametocyte
      specific expression of green fluorescent protein (GFP). In parasites transfected
      with a plasmid containing the Pfg14.748 5' flanking region immediately upstream
      of GFP, fluorescence was observed in a small number of schizonts the cycle before
      stage I gametocytes were observed. This expression pattern is consistent with
      commitment to sexual differentiation prior to merozoite release and erythrocyte
      invasion. Further investigation into the role of these genes in the transition
      from asexual to sexual differentiation could provide new strategies to block
      malaria transmission.

PMID- 15996768
TI  - Effect of total colectomy and PYY infusion on food intake and body weight in
      rats.
AB  - PYY (3-36) is postulated to act as a satiety factor in the gut-hypothalamic
      pathway to inhibit food intake and body weight gain in humans and rodent models.
      We determined the effect of 14-day continuous intravenous infusion of PYY (3-36)
      (175 microg/kg/day) on food intake and body weight gain in colectomized male
      Wistar rats. Colectomy caused an increase in plasma PYY levels at 7 days which
      was reduced at 14 days but still significantly elevated compared to basal
      preoperative values. Animals treated with continuous PYY (3-36) infusion had
      significantly elevated PYY levels compared to the control group throughout the
      whole experiment, but showed a similar pattern of food intake and body weight
      gain. In conclusion, although continuous intravenous infusion is the most
      physiologically relevant method to mimic high postprandial PYY levels, we did not
      observe any significant effect on food intake and body weight gain in non-food
      deprived colectomized animals. This suggests that PYY has, if at all, only a
      minor role in food intake in rats.

PMID- 15996769
TI  - Purification and characterization of antimicrobial peptides from the skin
      secretions of the carpenter frog Rana virgatipes (Ranidae, Aquarana).
AB  - The members of the Aquarana (or Rana catesbeiana species group) form a well
      supported monophyletic clade but phylogenetic relationships between species
      within the group are incompletely understood. Peptides that differentially
      inhibited the growth of bacteria were purified from electrically stimulated skin
      secretions of the carpenter frog Rana virgatipes. Structural characterization
      identified members of the ranatuerin-2 (3 peptides) and temporin (3-peptides)
      families, previously found in the skins of R. catesbeiana, R. clamitans, R.
      grylio and R. septentrionalis. Ranalexin, a peptide previously found only in the
      Aquarana, was isolated together with a variant (FFGLHNLVPSMLCVVRKKC) that lacks
      the propensity to adopt an alpha-helical conformation and so was devoid of
      antimicrobial activity. Two C-terminally alpha-amidated peptides belonging to the
      brevinin-2 family were isolated from the skin secretions that, like an ortholog
      from R. septentrionalis, lacked the C-terminal cyclic heptapeptide domain
      associated with members of this family. Ranatuerin-1, previously isolated from R.
      catesbeiana, R. clamitans and R. grylio but absent from R. septentrionalis, was
      also not identified in R. virgatipes. Synthetic replicates of temporin-1Va
      (FLSSIGKILGNLL.NH2), temporin-IVb (FLSIIAKVLGSLF.NH2) and temporin-1Vc
      (FLPLVTMLLGKLF.NH2) potently inhibited growth of Gram-positive bacteria
      (including methicillin-resistant Staphylococcus aureus). Temporin-1Va was also
      active against Gram-negative bacteria and the opportunistic yeast pathogen
      Candida albicans and had relatively weak hemolytic activity (LD50=120 microM) and
      may therefore represent a candidate for drug development. Our data support the
      placement of R. virgatipes in the Aquarana and indicate a closer phylogenetic
      relationship of R. virgatipes with R. septentrionalis than with R. catesbeiana,
      R. clamitans and R. grylio.

PMID- 15996770
TI  - Nitric oxide released by accessory cells mediates the gastrin-releasing peptide
      effect on murine lymphocyte chemotaxis.
AB  - Several neuropeptides, including gastrin-releasing peptide (GRP), modulate the
      immune response, specifically lymphocyte chemotaxis. In the present work the
      effect of GRP on the chemotaxis of murine lymphocytes from different immune
      locations in both, total leukocyte populations and populations depleted of
      adherent cells have been studied. Specificity of the GRP effect on chemotaxis
      using an antagonist of the GRP receptor, as well as the implication of nitric
      oxide (NO), using inhibitors of NO synthase and donors of NO, were investigated.
      The effects of GRP stimulating the chemotaxis of lymphocytes from peritoneum,
      axillary nodes and spleen and decreasing the chemotaxis from thymus were receptor
      specific and disappeared in lymphocytes from populations depleted of adherent
      cells. NO synthase inhibitors blocked the GRP effect on lymphocyte chemotaxis,
      and this action was reversed in the presence of l-arginine. Thus, the effect of
      GRP on murine lymphocyte chemotaxis appears to be mediated by NO secreted by
      adherent cells.

PMID- 15996771
TI  - Left ventricular mass and hypertrophy assessment by means of the QRS complex
      voltage-independent measurements.
AB  - ECG QRS-complex voltage-based criteria are relatively insensitive for detection
      of increased left ventricular mass (LVM). We developed and evaluate a new ECG
      index for LV hypertrophy (LVH) detection regardless of the QRS voltage. METHODS:
      Study population consisted of 106 patients (73 m, 33 f, aged 60 +/- 10 years)
      with established coronary artery disease (CAD). All patients had LVM assessed
      echocardiographically and indexed to BSA (LVMI(ECHO)). LVH was diagnosed if
      LVMI(ECHO) >117 g/m2 in men and >104 g/m2 in women. LV geometry was also
      determined. Analysed ECG variables, obtained from 12 leads recorded
      simultaneously, were: the QRS complex duration (QRSd, ms), the average 12-lead
      time to maximal deflection (TMD, ms), the average 12-lead QRS complex voltage
      (12QRSV, mV), the average product of 12 lead QRS voltage and duration (12QRSVd,
      mV ms), Sokolow-Lyon voltage and V-d product (SLV, SLVd), Cornell voltage and V-d
      product (CV, CVd). A newly developed index, LVM(ECG), was calculated, as LVM(ECG)
      = [(2 x TMD+QRSd/pi)3-(QRSd/pi)3]*0.0001 (ms3), and indexed to BSA (LVMI(ECG),
      ms3/m2). RESULTS: Means of the QRS voltage-related parameters were similar in
      patients with LVH and normal LVM. Greater differences existed between both groups
      when the QRS voltage-duration products were compared. LVMI(ECG) was most powerful
      in distinguishing between groups (130 +/- 33 LVH vs 91 +/- 21 normal LVM, p <
      0.001). LVMI(ECG) correlated with LVMI(ECHO) better (r = 0.77, p < 0.001) than
      other indices (r coefficients between 0.24 for SLV and 0.49 for CVd). None of the
      examined indices allowed for distinction between eccentric and concentric LVH.
      The new index showed better statistical performance (area under ROC = 0.861)
      compared to the other indices (AUC range 0.545-0.697, p<0.001 vs LVMI(ECG)). At
      the specificity level of 92%, the value of LVMI(ECG) > 120 ms3/m2 had the
      sensitivity of 64% for detection of increased LVM. The sensitivities of the other
      parameters were significantly lower (sensitivity range 18-42%). Relative intra-
      and interobserver errors and correlation coefficients for LVMI(ECG) calculation
      were 0.4% and 1.6% and r = 0.94 and 0.98, respectively. CONCLUSIONS: In patients
      with CAD an assessment of LV mass and detection of hypertrophy using the QRS
      complex time-dependent index is feasible. The new index correlated well with
      echocardiographically-determined LVM and showed better statistical performance
      than indices which include QRS-voltage measurements. The results are promising
      and warrant further studies to evaluate the utility of the new index as a risk
      predictor.

PMID- 15996772
TI  - Phenytoin can accelerate the healing process after experimental myocardial
      infarction?
AB  - BACKGROUND: Over-degradation and/or inadequate accumulation of extracellular
      matrix after myocardial infarction (MI) may lead to adverse ventricular
      remodeling, even ventricular aneurysm or rupture. Phenytoin can increase gingival
      overgrowth by stimulating the proliferation of connective tissue, which implies a
      novel way to hasten the healing process after MI. METHODS: Experimental MI was
      induced by permanent coronary ligation. Surviving rats after MI were randomly
      divided into phenytoin, captopril, phenytoin plus captopril, operation control
      and sham operation group. Picrosirius red staining plus polarized microscopy was
      used for collagen analysis. Left ventricular passive pressure-volume relationship
      was determined ex vivo. The effects of phenytoin concentration gradient (0, 1.25,
      2.5, 5.0, 10.0, and 20.0 microg/mL) on transforming growth factor-beta1 (TGF
      beta1) mRNA and protein expression by neonatal rat cardiac fibroblast were
      determined using semi-quantitative RT-PCR and ELISA, respectively. Peritoneal
      macrophage was incubated with same gradient of phenytoin concentration. Then the
      supernatant was harvested to stimulate another 6 groups of cardiac fibroblast, to
      investigate possible role mediated by macrophage. RESULTS: Phenytoin treatment
      could promote type I collagen cross-linking level and ratio of type I/III
      collagen in the infarcted region and had no obvious side effect on interstitial
      collagen volume fraction, subtype ratio and distribution in non-infarcted region.
      Phenytoin-treated hearts exhibited attenuation of global ventricular dilation.
      Phenytoin alone had no direct effects on rat cardiac fibroblast proliferation and
      collagen production in vitro, but phenytoin-stimulated macrophage could exert a
      positive influence on cardiac fibroblast TGF-beta1 mRNA and protein production,
      which exhibited a dose-dependent manner. CONCLUSIONS: Phenytoin can accelerate
      the healing process in the infarcted region and has no obviously detrimental
      influence on collagen accumulation in non-infarcted region, which implies a
      potential benefit to patients undergoing early post-infarction ventricular
      remodeling process.

PMID- 15996773
TI  - Isolated noncompaction of left ventricle presenting as peripartum cardiomyopathy.
AB  - Long term follow-up of the first reported case of isolated noncompaction of left
      ventricle presenting as peripartum cardiomyopathy is presented.

PMID- 15996774
TI  - Transient mid-ventricular ballooning cardiomyopathy: a new entity of Takotsubo
      cardiomyopathy.
AB  - We present a case of a 64-year-old man with transient mid-ventricular ballooning
      cardiomyopathy. Left ventriculography showed morphological differences with
      ballooning around the whole mid-portion of the left ventricle, although
      precipitating factors and clinical courses were similar to Takotsubo
      cardiomyopathy. We suspect that transient mid-ventricular ballooning
      cardiomyopathy is a new pathological entity in Takotsubo cardiomyopathy.

PMID- 15996775
TI  - Intracavitary left ventricular hydatid cysts ruptured during cardiopulmonary
      resuscitation in a patient with acute myocardial infarction.
AB  - Cardiac hydatid cyst is a rare complication of parasitic infection caused by
      Echinococcus granulosus. Cardiac involvement occurs in only 0.2-2% of hydatidosis
      cases. Rupture of hydatid cysts into cardiac chambers is very rare. In this
      report, we present a case of intracavitary left ventricular hydatid cysts
      ruptured during cardiopulmonary resuscitation in a patient with acute myocardial
      infarction.

PMID- 15996776
TI  - Impact of left ventricular hypertrophy late after aortic valve replacement for
      aortic stenosis on cardiovascular morbidity and mortality.
AB  - AIMS: The goal of this study was to assess the prevalence of left ventricular
      (LV) hypertrophy in patients with aortic stenosis late (>6 months) after aortic
      valve replacement and its impact on cardiac-related morbidity and mortality.
      METHODS AND RESULTS: In a single tertiary centre, echocardiographic data of LV
      muscle mass were collected. Detailed information of medical history and
      angiographic data were gathered. Ninety-nine of 213 patients (46%) had LV
      hypertrophy late (mean 5.8 +/- 5.4 years) after aortic valve replacement. LV
      hypertrophy was associated with impaired exercise capacity, higher New York Heart
      Association dyspnoea class, a tendency for more frequent chest pain expressed as
      higher Canadian Cardiovascular Society class, and more rehospitalizations. 24% of
      patients with normal LV mass vs. 39% of patients with LV hypertrophy reported
      cardiac-related morbidity (p = 0.04). In a multivariate logistic regression
      model, LV hypertrophy was an independent predictor of cardiac-related morbidity
      (odds ratio 2.31, 95% CI 1.08 to 5.41), after correction for gender, baseline
      ejection fraction, and coronary artery disease and its risk factors. Thirty seven
      deaths occurred during a total of 1959 patient years of follow-up (mean follow-up
      9.6 years). Age at aortic valve replacement (hazard ratio 1.85, 95% CI 1.39 to
      2.47, for every 5 years increase in age), coexisting coronary artery disease at
      the time of surgery (hazard ratio 3.36, 95% CI 1.31 to 8.62), and smoking (hazard
      ratio 4.82, 95% CI 1.72 to 13.45) were independent predictors of overall
      mortality late after surgery, but not LV hypertrophy. CONCLUSIONS: In patients
      with aortic valve replacement for isolated aortic stenosis, LV hypertrophy late
      after surgery is associated with increased morbidity.

PMID- 15996777
TI  - Power and coherent oscillations distinguish REM sleep, stage 1 and wakefulness.
AB  - The objective of this work is to determine differences in spectral power and
      coherent activity between stage 1 (S1) and REM sleep. The EEG activity of the two
      sleep stages is almost indistinguishable by visual inspection. Although many
      efforts have been directed toward understanding the process of falling asleep,
      little is known about differences in EEG activity between stage 1 (S1) and REM
      sleep. Polysomnography of 8 healthy young adults from S1, REM sleep and
      wakefulness was recorded. Spectral power and spectral correlation were obtained
      for 1-50 Hz. Stage 1 was distinguished (ANOVAs) from REM sleep by lower power in
      1-9 Hz, higher power in alpha, beta and gamma, lower interhemispheric correlation
      in 1-8 Hz and gamma, and higher right correlation in 30-50 Hz. It differed from
      wakefulness by lower power in 9-50 Hz, but not in 1-8 Hz, or in inter- and
      intrahemispheric correlation. EEG differences between S1 and REM sleep reside not
      only in changes in power but also in coherent activity. The different behavior of
      slow and fast frequencies suggests two different mechanisms involved in the gate
      into sleep, one implicated in promoting sleep, the thalamo-cortical oscillator
      mode and the other in reducing alertness involving activation mechanisms. Stage 1
      is a mixed state, alertness is already reduced but sleep-promoting mechanisms are
      not yet fully installed. The EEG differences between these two sleep stages
      contribute to the understanding of REM sleep and S1 physiology and may be
      relevant for understanding disorders in falling asleep.

PMID- 15996778
TI  - Spatial learning and long-term potentiation of mutant mice lacking D-amino-acid
      oxidase.
AB  - We evaluated the role of D-amino-acid oxidase on spatial learning and long-term
      potentiation (LTP) in the hippocampus, since this enzyme metabolizes D-amino
      acids, some of which enhance the N-methyl-D-aspartate receptor functions. The
      Morris water maze learning and the LTP in the CA1 area of the hippocampal slice
      were observed in wild-type mice and mutant mice lacking D-amino-acid oxidase. The
      mutant mice showed significantly shorter platform search times in the water maze
      and significantly larger hippocampal LTPs than the wild-type mice. These results
      suggest that the abundant D-amino-acids in the mutant mouse brain facilitate
      hippocampal LTP and spatial learning.

PMID- 15996779
TI  - Fraxetin prevents rotenone-induced apoptosis by induction of endogenous
      glutathione in human neuroblastoma cells.
AB  - Fraxetin belongs to an extensive group of natural phenolic anti-oxidants. In the
      present study, using a human neuroblastoma SH-SY5Y cells, we have investigated
      the protective effects of this compound on modifications in endogenous reduced
      glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on
      rotenone-mediated cytoxicity. Incubation of cells with the fraxetin led to a
      significant elevation dose-dependent of cellular GSH and this was accompanied by
      a marked protection against rotenone-mediated toxicity, which was also
      significantly reversed in the cells with buthionine sulfoximine (BSO) co
      treatment. Taken together, this study suggested that intracellular GSH appeared
      to be an important factor in fraxetin-mediated cytoprotection against rotenone
      toxicity in SH-SY5Y cells. Fraxetin at 10-100 muM inhibited the formation of ROS,
      cytochrome c release, activation of caspase-3 and 9, and suppressed the up
      regulation of Bax, whereas no significant change occurred in Bcl-2 levels. Our
      results indicated that the anti-oxidative and anti-apoptotic properties render
      this natural compound potentially protective against rotenone-induced
      cytotoxicity.

PMID- 15996780
TI  - Detection of Campylobacter jejuni in naturally contaminated chicken skin by
      melting peak analysis of amplicons in real-time PCR.
AB  - Contamination of poultry by Campylobacter spp. is a significant source of human
      diarrheal diseases. Traditional methods currently used to detect Campylobacter in
      foods are time-consuming and labor-intensive. In this study, primers designed for
      the Campylobacter jejuni cadF gene sequence were used in a SYBR Green I real-time
      PCR assay as an alternative to a conventional bacteriological method for the
      rapid detection of C. jejuni from poultry. Twelve portions of chicken purchased
      from two local grocery stores and 39 portions obtained from a commercial
      processing plant were examined. Samples of the skin were enriched in Bolton broth
      at 37 degrees C for 3 h and then at 42 degrees C for 9, 21, or 45 h under
      microaerobic conditions. DNA was extracted from 1-ml aliquots of the enrichment
      cultures using 1% Triton X-100. The DNA was used as the template in a real-time
      polymerase chain reaction (PCR) assay. After 24 h of enrichment, C. jejuni was
      isolated from 13 samples and all of the positive cultures were also detected by
      the real-time PCR procedure. C. jejuni was detected by both methods from samples
      artificially contaminated with 1 or 10 CFU of C. jejuni per 10 g, after 24 h of
      enrichment. The real-time PCR method was found to be sensitive and specific. It
      significantly reduced the time required for the detection of C. jejuni in poultry
      following enrichment of samples.

PMID- 15996781
TI  - Thermal inactivation of the wine spoilage yeasts Dekkera/Brettanomyces.
AB  - The heat resistance of three strains of Dekkera/Brettanomyces (Dekkera anomala
      PYCC 5,153, Dekkera bruxellensis PYCC 4,801 and Dekkera/Brettanomyces 093) was
      evaluated at different temperatures between 32.5 and 55 degrees C. Thermal
      inactivation tests were performed in tartrate buffer solution (pH 4.0) and in
      wines. In the studies employing buffer as the heating menstruum, measurable
      thermal inactivation began only at temperatures of 50 degrees C. When heating was
      performed in wine, significant inactivation begins at 35 degrees C. Subsequent
      thermal inactivation tests were performed in buffer at various levels of pH,
      ethanol concentration, and various phenolic acids. Results from experiments in
      buffer with added ethanol suggest that the greater heat sensitivity shown in
      wines can be largely attributed to ethanol, although potentiation of this effect
      might be due to the phenolic content, particularly from ferulic acid. In the
      range of pH values tested (2.5-4.5), this factor had no influence in the heat
      inactivation kinetics. Relevant data, in the form of D and Z values calculated in
      the various environments, potentially useful for the establishment of regimes of
      thermal control of Dekkera/Brettanomyces yeasts in wine and contaminated
      equipment is presented.

PMID- 15996782
TI  - Cellobiose dehydrogenase formation by filamentous fungus Chaetomium sp. INBI 2
      26(-).
AB  - Laccase-negative filamentous fungus INBI 2-26(-) isolated from non-sporulating
      laccase-forming fungal association INBI 2-26 by means of protoplast technique was
      identified as Chaetomium sp. based on partial sequence of its rRNA genes. In the
      presence of natural cellulose sources, the strain secreted neutral cellobiose
      dehydrogenase (CDH) activity both in pure culture and in co-culture with laccase
      positive filamentous fungus INBI 2-26(+) isolated from the same association. INBI
      2-26(-) also secreted CDH during submerged cultivation in minimal medium with
      glucose as the sole carbon source. Maximal CDH activity of 1IU/ml at pH 6 with
      2,6-dichlorophenolindophenol (DCPIP) as an acceptor was obtained on 12th day of
      submerged cultivation with filter paper as major cellulose source. Cellulase
      system of Chaetomium sp. INBI 2-26(-) capable of adsorption onto H(3)PO(4)
      swollen filter paper consisted of four major proteins (Mr 200, 95, 65 and 55K)
      based on SDS-polyacrylamide gel electrophoresis and was capable of DCPIP
      reduction without exogenous cellobiose.

PMID- 15996783
TI  - The influence of different cultivation conditions on the metabolome of Fusarium
      oxysporum.
AB  - The two most widespread pentose sugars found in the biosphere are d-xylose and l
      arabinose. They are both potential substrates for ethanol production. The purpose
      of this study was to better understand the redox constraints imposed to Fusarium
      oxysporum during utilization of pentoses. In order to increase ethanol yield and
      decrease by-product formation, nitrate was used as nitrogen source. The use of
      NADH, the cofactor in denitrification process when using nitrate as a nitrogen
      source, improved the ethanol yield on xylose to 0.89 mol mol(-1) compared to the
      ethanol yield achieved using ammonium as nitrogen source 0.44 mol mol(-1). The
      improved ethanol yield was followed by a 28% decrease in yield of the by-product
      xylitol. In order to investigate the metabolic pathway of arabinose and the
      metabolic limitations for the efficient ethanol production from this sugar, the
      extracellular and intracellular metabolite profiles were determined under aerobic
      and anaerobic cultivation conditions. The results of this study clearly show
      difficulties in channelling of glucose-1-P (G1P) to pentose phosphate pathway
      (PPP) and reduced NADPH regeneration, suggesting that NADPH becomes a limiting
      factor for arabinose conversion, resulting in excessive acetate production.
      Variations of the fungus intracellular amino and non-amino acid pool, under
      different culture conditions, were evaluated using principal component analysis
      (PCA). PCA projection of the metabolome data collected from F. oxysporum
      subjected to environmental perturbations succeeded to visualize different
      physiological states and the conclusions of this study were that the metabolite
      profile is unique according to: (1) the carbon source and (2) the oxygen supply,
      and to a lesser extent to the cultivation phase.

PMID- 15996784
TI  - A novel flow cytometry-based method for analysis of expression levels in
      Escherichia coli, giving information about precipitated and soluble protein.
AB  - A high throughput method for screening of protein expression is described. By
      using a flow cytometer, levels of both soluble and precipitated protein can
      simultaneously be assessed in vivo. Protein fragments were fused to the N
      terminus of enhanced GFP and the cell samples were analysed using a flow
      cytometer. Data concerning whole cell fluorescence and light scattering was
      collected. The whole cell fluorescence is probing intracellular concentrations of
      soluble fusion proteins. Concurrently, forward scattered light gives data about
      inclusion body formation, valuable information in process optimisation. To
      evaluate the method, the cells were disrupted, separated into soluble and non
      soluble fractions and analysed by gel electrophoresis. A clear correlation
      between fluorescence and soluble target protein was shown. Interestingly, the
      distribution of the cells regarding forward scatter (standard deviation)
      correlates with the amount of inclusion bodies formed. Finally, the newly
      developed method was used to evaluate two different purification tags, His(6) and
      Z(basic), and their effect on the expression pattern.

PMID- 15996785
TI  - Development of a software tool for in silico simulation of Escherichia coli using
      a visual programming environment.
AB  - This study describes the development of a software tool, EcoSim, to assist users
      in implementing quantitative in silico simulation easily. It consists of four
      parts: extracellular environment and constraints setting mode, table for optimal
      metabolic flux distribution and chart for changes of substrate concentration,
      dynamic flux distribution viewer and dynamic hierarchical regulatory network
      viewer. Representation of a hierarchical regulatory network was constructed with
      defined modeling symbols and weight in the central Escherichia coli metabolism.
      All programming procedures for EcoSim were accomplished in a visual programming
      environment (LabVIEW). To illustrate quantitative in silico simulation with
      EcoSim, this program was performed on E. coli using glucose and acetate as carbon
      sources. The simulation results were in agreement with the experimental data
      obtained from the literature. EcoSim can be used to assist biologists and
      engineers in predicting and interpreting dynamic behaviors of E. coli under a
      variety of environmental conditions.

PMID- 15996786
TI  - Analysis of adenovirus gene transfer into adult neural stem cells.
AB  - Adult neural stem cells (aNSCs) represent an attractive source for the production
      of specific types of neurons in degenerative CNS diseases and for the development
      of new regenerative gene therapies. However, the use of adult NSCs for
      transplantation and gene replacement strategies requires efficient gene
      expression in the cells. Due to the low pathogenicity of adenovirus (Ad) for
      humans, its large delivery capacity, and long-term transgene expression, Ad
      vectors are widely used. Here, we tested the potential of the Ad vector system to
      transduce adult NSCs. Analysis of Ad receptor expression in primary aNSCs
      revealed a complete lack of the coxsackie-adenovirus receptor and no or low
      expression of alphanu- and beta5-integrins, respectively, on mRNA and protein
      level. Consistently, transduction at different multiplicities of infection using
      an Ad vector expressing the enhanced green fluorescent protein (GFP) showed that
      adult NSCs are particularly resistant to Ad infection even at highest MOI (1000)
      in contrast to differentiated types of neural cells.

PMID- 15996787
TI  - Receptor-binding properties of swine influenza viruses isolated and propagated in
      MDCK cells.
AB  - To study the receptor specificities of H1 and H3 influenza viruses isolated
      recently from pigs, we employed the analogues of natural receptors, namely
      sialyloligosaccharides conjugated with polyacrylamide in biotinylated and label
      free forms. All Madin-Darby canine kidney (MDCK) cell-propagated viruses with
      human H3 or classical swine H1 hemagglutinins bound only to Neu5Acalpha2
      6Galbeta1-bearing polymers, and not to Neu5Acalpha2-3Galbeta1-bearing polymers.
      This receptor-binding pattern is typical for human influenza viruses and it
      differs from the previously described receptor-binding specificity of egg-adapted
      swine influenza viruses. Swine virus isolates with avian-like H1 and H3
      hemagglutinins displayed distinct receptor specificity by binding to both
      Neu5Acalpha2-6Gal- and Neu5Acalpha2-3Gal-containing receptors. These viruses, as
      well as egg-adapted swine and turkey viruses with a classical swine HA, differed
      from the related duck viruses by increased affinity to sulfated
      sialyloligosaccaride, Su-SiaLe(x). Except for avian-like H3 viruses, none of the
      studied swine viruses bound to Neu5Gc-containing sialoglycopolymers, suggesting
      that binding to these sialic acid species abundantly expressed in pigs may not be
      essential for virus replication in this host.

PMID- 15996788
TI  - Serological characterization of novel P11[14],G8 bovine group A rotavirus, Sun9,
      isolated in Japan.
AB  - In this study, a novel bovine group A rotavirus (BoRV-A), Sun9, isolated from
      calf diarrhea in Tochigi Prefecture, Japan, was serologically characterized by a
      cross-neutralization assay, and serological surveillance by using its reassortant
      was performed on cattle bred in Japan. The G serotype of Sun9 was identified as G
      serotype 8 based on the one- or two-way serological relationships observed in
      Sun9 and other G8 strains. The P serotype of Sun9 was identified as P serotype 11
      based on the one- or two-way serological relationships observed in Sun9, its
      reassortants, and the P11 lapine group A rotavirus R-2. The serological
      surveillance data indicated that 2.4% of the specimens appeared to possess
      antibodies against the P11[14] antigen. Few P11[14] bovine group A rotaviruses
      may exist in the Japanese cattle population.

PMID- 15996789
TI  - Search for substrates for prolyl oligopeptidase in porcine brain.
AB  - The function of prolyl oligopeptidase (PO) has been associated with several
      disorders of the central nervous system. The purpose of this study was to
      identify endogenous substrates for recombinant porcine PO in porcine brain. The
      smaller polypeptides were extracted from total brain homogenates and fractionated
      by two-dimensional chromatography prior to incubation with PO. Shifts in the mass
      spectrum between the control and the incubated sample, marked potential
      substrates. Using MSMS peptide sequencing techniques, we identified several
      fragments of intracellular proteins as potential substrates, which opens new
      perspectives for finding the function of PO in the intracellular space.

PMID- 15996790
TI  - Discovery that a melanocortin regulates sexual functions in male and female
      humans.
AB  - Melanocortins (MCs) are multifunctional peptide hormones that regulate a
      diversity of physiological functions. MCs have been implicated in sexual function
      in animals. We document here that a MC analog, Melanotan II (MTII), can enhance
      sexual function in human males (erectile activity) and females (increased levels
      of sexual desire and genital arousal). Unlike other sexual-enhancement drugs,
      MTII works at the level of the brain, thus eliciting a rather natural sexual
      response with minimal or no undesirable side effects. The actions of the peptide
      were discovered accidentally while studying the effects of the peptide and
      related analogs on human skin pigmentation (tanning).

PMID- 15996791
TI  - Agouti-related protein: more than a melanocortin-4 receptor antagonist?
AB  - It is well established that agouti-related protein (AGRP) can act as a
      competitive antagonist to proopiomelanocortin (POMC)-derived peptides at the
      melanocortin-4 receptor (MC4R), and that this homeostatic mechanism is important
      as a means of coordinating appetite with perceived metabolic requirement.
      However, there are clearly additional facets to the physiological role of AGRP,
      given that it is active in MC4R knockout mice and it has strikingly long-lasting
      effects on food intake, compared with MC4R agonists. In this review we focus on:
      (i) evidence that AGRP is more sensitive to perturbations in energy balance than
      POMC and is therefore the primary basis of melanocortinergic regulation. (ii)
      Evidence that the bioactive peptide AGRP83-132, acts by alternate mechanism(s) to
      elicit its long-term effects on food intake. (iii) Evidence that AGRP is post
      translationally cleaved to generate AGRP83-132 and one or more N terminal
      peptides, which may have an important physiological role(s) that are independent
      of the melanocortin system. A clear understanding of how proAGRP processing is
      regulated, and the role of resultant peptides, may define additional therapeutic
      targets in the treatment of obesity.

PMID- 15996792
TI  - Novel frenatins from the skin of the Australasian giant white-lipped tree frog,
      Litoria infrafrenata: cloning of precursor cDNAs and identification in defensive
      skin secretion.
AB  - The Australasian anuran amphibian genus Litoria, contains many phenotypically
      diverse species as a result of radial evolution of an ancestral species into
      different biotopes much in the manner of the indigenous marsupial mammals. In
      common with members of the Central/South American genus Phyllomedusa, their
      specialized skin granular glands are factories for the production of a plethora
      of biologically-active peptides. Here we report a more detailed study of those
      present in the defensive skin secretion of the Australasian giant white-lipped
      tree frog, Litoria infrafrenata, and, for the first time, we have identified
      three novel frenatins by deduction of primary structures from cDNAs that were
      cloned from a library constructed from lyophilized skin secretion using a
      recently-developed technique. All open-reading frames consisted of a putative
      signal peptide and an acidic pro-region followed by a single copy of a frenatin
      peptide. Processed peptides corresponding in molecular mass to the deduced
      molecular masses of frenatins (named 1.1, 3, 3.1 and 4.1) were identified in the
      same secretion sample using HPLC and mass spectroscopy. The application of this
      technique thus permits parallel peptidomic and transcriptomic analyzes on the
      same lyophilized skin secretion sample circumventing sacrifice of specimens from
      endangered herpetofauna.

PMID- 15996793
TI  - Proteomics analysis provides insight into caloric restriction mediated oxidation
      and expression of brain proteins associated with age-related impaired cellular
      processes: Mitochondrial dysfunction, glutamate dysregulation and impaired
      protein synthesis.
AB  - Age-related impairment of functionality of the central nervous system (CNS) is
      associated with increased susceptibility to develop many neurodegenerative
      diseases. Increased oxidative stress in the CNS of aged animals is manifested by
      increased protein oxidation, which is believed to contribute to the age-related
      learning and memory deficits. Glutamate dysregulation, mitochondrial dysfunction
      and impaired protein synthesis are observed in aged brains, along with increased
      protein oxidation. Interestingly, all of these age-related cellular alterations
      can be improved by caloric restriction (CR), which can also improve the
      plasticity and recovery of the CNS. Although the beneficial effects of CR on
      brains are well established, the mechanism(s) of its action remains unclear. In
      order to gain insight into the mechanism of CR in the brain, we located the brain
      regions that are benefited the most from reduced oxidative stress by CR. Along
      with other brain regions, striatum (ST) showed significantly decreased bulk
      protein carbonyl levels and hippocampus (HP) showed decreased bulk protein 3
      nitrotyrosine (3-NT) levels in CR aged rats when compared to those of age matched
      controls. To determine which proteins were oxidatively modified in these brain
      regions, we used parallel proteomics approach to identify the proteins that are
      altered in oxidation and expression. The specific carbonyl levels of pyruvate
      kinase M2 (PKM2), alpha-enolase (ENO1), inositol monophosphatase (INSP1), and F1
      ATPase Chain B (ATP-F1B) were significantly decreased in ST of aged CR rats. In
      contrast, the expression levels of phosphoglycerate kinase 1 (PKG1), inosine
      monophosphate cyclohydrolase (IMPCH) and F1-ATPase Chain A (ATP-F1A) were
      significantly increased in the ST of CR rats. In the hippocampus of CR rats, the
      specific 3-NT levels of malate dehydrogenase (MDH), phosphoglycerate kinase 1
      (PKG1) and 14-3-3 zeta protein were significantly decreased and expression levels
      of DLP1 splice variant 1 (DLP1), mitochondrial aconitase (ACO2), dihydrolipoamide
      dehydrogenase (DLDH), neuroprotective peptide H3 (NPH3), and eukaryotic
      translation initiation factor 5A (eIF-5A) are increased. Moreover, an unnamed
      protein product (UNP1) with similar sequence to initiation factor 2 (IF-2) was
      decreased in the HP of CR rats. Our data support the hypothesis that CR induces a
      mild metabolic stress response by increasing the production of neurotrophic
      proteins, therefore, priming neurons against apoptosis. Moreover, our study shows
      that the improvement of glutamate dysregulation, mitochondrial dysfunction and
      protein synthesis by CR is, at least partially, due to the CR-mediated alteration
      of the oxidation or the expression of PKM2, ENO1, INSP1, ATP-F1B, PKG1, IMPCH,
      ATP-F1A MDH, PKG1 and 14-3-3 zeta protein, DLP1, ACO2, DLDH, NPH3, eIF-5A and
      UNP1. This study provides valuable insights into the mechanisms of the beneficial
      factors on brain aging by CR.

PMID- 15996794
TI  - Involvement of the GABAergic system in depressive symptoms of Alzheimer's
      disease.
AB  - Cognitive and neuropsychiatric (BPSD) symptoms seen in Alzheimer's disease (AD)
      probably result from differential neurotransmitter alterations. The involvement
      of the glutamatergic and GABAergic system in cognitive and behavioral and
      psychological symptoms of dementia (BPSD) has been studied in post-mortem frontal
      and temporal cortex from AD patients who had been prospectively assessed with the
      Mini-Mental State Examination (MMSE) for cognitive impairment and with the
      Present Behavioral Examination (PBE) for BPSD. In addition to cholinergic
      deficits, significant decreases in gamma-amino butyric acid (GABA) content, with
      no changes in glutamate content, were found in frontal and temporal cortex. Both
      GABA levels and the glutamate/GABA ratio showed significant correlations with
      depression in AD. In the temporal cortex, higher densities of
      GABA(A)/benzodiazepine receptors also correlated with more severe depression. It
      can be suggested that in a situation of cholinergic deficit, such as AD, an
      imbalance between the excitatory glutamatergic tone and inhibitory GABAergic tone
      may be responsible for non-cognitive behavioral disturbances.

PMID- 15996796
TI  - A synthetic gonadotropin-releasing hormone (GnRH) vaccine for control of
      fertility and hormone dependent diseases without any adjuvant.
AB  - Active immunization against self-peptides have gained widespread acceptance
      inspite of their low immunogenicity. Recent applications involving multiple
      copies of self-peptides in linear alignment and conjugation with carrier proteins
      appear to increase the immune response against self-peptides. As with most
      vaccines, however, immunogens require supplementation with adjuvants to elicit an
      optimum immune response. In the present study, we prepared a double-chain mini
      protein with each chain containing three linear repeats of the self-peptide
      gonadotropin-releasing hormone (GnRH3), the hinge region of human IgG1 (hinge),
      and a T-helper epitope from the measles virus protein (MVP). The GnRH3-hinge-MVP
      mini-protein was conjugated to purified recombinant heat shock protein 65 (Hsp
      65) of Mycobacterium bovis and used to immunize rats primed with subcutaneous
      injections of Bacillus Calmette-Guerin (BCG) in the absence of adjuvants. The
      GnRH3-hinge-MVP-Hsp 65 stimulated the production of specific anti-GnRH antibodies
      in the absence of adjuvants and the antibody titer was comparable to that
      produced in rats immunized with the dimeric mini-protein in the presence of
      Freund's adjuvant. Moreover, immunization with the adjuvant-free GnRH3-hinge-MVP
      Hsp 65 induced degeneration of the reproductive organs in both male and female
      rats unlike those immunized in the absence of Hsp 65 or in control animals
      inoculated with the vehicle only. Histological examination of the affected organs
      showed atrophy of the seminiferous tubules with diminished spermatogenesis in the
      testes of male rats. In female rats, the uteri were much smaller in size and the
      ovaries exhibited reduced follicular development. These findings demonstrated
      that GnRH3-hinge-MVP-Hsp 65 mounted a strong immune response in the absence of
      conventional adjuvants, and could prove useful in control of fertility and the
      treatment of conditions/diseases where GnRH ablation is required.

PMID- 15996797
TI  - Detection of secondary mumps vaccine failure by means of avidity testing for
      specific immunoglobulin G.
AB  - The aim of this study was to discriminate between primary and secondary vaccine
      failure in children with mumps using IgG avidity testing. Thirty-nine serum
      samples from children with mumps, confirmed by specific IgM, were studied. The
      patients were grouped according to their immunization status. The secondary
      immune response was defined by IgG with an avidity index >32%. A secondary
      response in infected children previously immunized was considered as a secondary
      vaccine failure. Vaccinated children presented higher IgG titers and IgG avidity
      than unvaccinated children. The proportion of secondary immune responses in
      unvaccinated patients was lower than that obtained in previously vaccinated
      infected patients. Avidity testing can be a useful tool to detect secondary
      vaccine failure in mumps.

PMID- 15996798
TI  - Biomechanical stability of high tibial opening wedge osteotomy: internal fixation
      versus external fixation.
AB  - PURPOSE: The goal of our study was to evaluate stability of internal fixation
      with a plate compared to external fixation in an opening wedge high tibial
      osteotomy model. Significance. To our knowledge, this is the only study to
      compare internal plate to external fixation in an opening wedge osteotomy model.
      The design of this cadaver study limits its direct application to clinical
      practice. MATERIAL AND METHOD: In each of the six pairs of fresh-frozen human
      cadaver knees one specimen was randomly assigned to internal plate fixation while
      the other was stabilized with an external fixation. The osteosynthesis plate
      incorporated a 12.5mm block that distracted the medial tibial cortices. Each knee
      was loaded on a mechanical testing machine to 700 N for 10,000 cycles to simulate
      immediate full weight bearing in a walking individual. SUMMARY OF RESULTS: The
      internal plate osteosynthesis provided significantly greater stiffness and
      smaller loss of correction (1.60mm) than the external fixation (3.22 mm) under
      cyclic loading condition (P<0.05). For static loading, the mean value of
      stiffness resulting in failure for the internal plate and external fixation, were
      respectively, 938 N/mm and 459 N/mm. Load to failure also showed two times
      greater stiffness in the plate osteosynthesis group. No hardware failure was
      observed in either construct. DISCUSSION AND CONCLUSION: Plate fixation was
      superior to external fixation in maintaining correction. However, progressive
      adjustment of the distraction with the external fixator allows precise "fine
      tuning" during the healing process that is not possible with internal fixation.

PMID- 15996799
TI  - A comparison of the 1-step, 2-step, and 3-step protocols for obtaining barefoot
      plantar pressure data in the diabetic neuropathic foot.
AB  - BACKGROUND: Barefoot plantar pressure measurements are routinely used in the risk
      evaluation for ulceration in diabetic patients with neuropathy. The aim was to
      compare three step-protocols commonly used for pressure assessment in these
      patients. METHODS: Dynamic barefoot plantar pressures were measured in 14
      diabetic neuropathic patients (vibration perception threshold >35 V) contacting a
      pressure platform on the first, second or third step after gait initiation. Ten
      repeated trials per step-protocol were collected. The 3-step protocol was
      regarded the reference protocol. Peak pressure, pressure-time integral and
      contact time were calculated for each of six anatomical foot regions. Intraclass
      correlation coefficients (ICC) were calculated to assess reliability in each
      protocol. FINDINGS: Regional peak pressures and pressure-time integrals were not
      significantly different between protocols. Contact time was significantly
      different in the heel region between the 1-step and 3-step protocol only
      (P<0.05). Intraclass correlation coefficients for the maximum 10 repeated trials
      were high (>0.87) and similar between protocols. Reliable estimates (ICC>0.85) of
      peak pressure were achieved with three repeated trials in the 2-step protocol,
      and four in the other two; for pressure-time integral these numbers were 7 (1
      step), 4 (2-step), and 5 trials (3-step). INTERPRETATION: Barefoot plantar
      pressures in the diabetic neuropathic foot can be assessed in a reproducible
      manner with any of the step-protocols used. For this purpose, the 1-step and 2
      step protocols prove to be valid methods. A 2-step protocol requires the least
      amount of repeated trials for obtaining reliable pressure data and may be
      recommended for assessment of these patients.

PMID- 15996800
TI  - Cervical muscles weakness in chronic whiplash patients.
AB  - BACKGROUND: Isometric cervical strength has been used for assessing the severity
      of cervical spine pathologies. However there is a conspicuous dearth of
      information relating to cervical strength data in patients suffering from chronic
      whiplash. Therefore the objective of this study was to compare absolute and ratio
      based isometric cervical strength scores in chronic whiplash patients with
      reported corresponding scores in healthy subjects. METHODS: Isometric cervical
      strength was measured in the directions of flexion, extension, right and left
      lateral flexion in 97 patients, 51 women and 46 men, using a wall-mounted
      dynamometer. FINDINGS: Compared to published values of normal subjects, whiplash
      patients suffered sharp reductions of about 90% in both genders and in all
      directions. The consistency of the isometric cervical strength scores as
      indicated by the mean coefficient of variation was relatively low, 17% and 20% in
      men and women respectively. The flexion/extension strength ratio ranged 0.8--0.9,
      slightly higher than the reported range for normal subjects. This ratio was
      highly correlated (r=0.91, P=0.01) with the mean coefficient of variation in a
      subgroup of 9 patients. INTERPRETATION: In the absence of an obvious reason such
      as sever atrophy or grossly dysfunctional neurological control the indicated
      weakness of the cervical muscles may be associated with learned pain avoidance
      behavior which is typical among this group of patients.

PMID- 15996801
TI  - Effects of a mixture of tetracyclines to Lemna gibba and Myriophyllum sibiricum
      evaluated in aquatic microcosms.
AB  - The impact of a mixture of oxytetracycline, chlortetracycline, tetracycline and
      doxycycline on Myriophyllum sibiricum and Lemna gibba was investigated using
      fifteen 12,000-L microcosms (k=5, n=3). Significant concentration-response
      relationships were only found for M. sibiricum, where dry mass was 69, 47, 30,
      and 7% of controls at respective treatment concentrations of 0.080, 0.218, 0.668,
      and 2.289 micromol/L. Somatic endpoints were strongly and negatively correlated
      with percent light transmission, except plant length, which was positively
      correlated. Treated microcosms experienced a reduction in the percent of surface
      irradiance penetrating the water column as high as 99.8% at a depth of 70 cm,
      relative to controls. Position relative to the water column was likely
      responsible for the differential effects observed between floating (L. gibba) and
      submerged (M. sibiricum) species of macrophytes. A hazard quotient assessment of
      the lowest EC10 value indicated significant risk, exceeding the critical HQ
      value, but not the lowest EC25 value.

PMID- 15996802
TI  - Treatment of log yard run-off by irrigation of grass and willows.
AB  - Log yard run-off is a potential environmental risk, among other things because it
      creates an oxygen deficiency in receiving watercourses. This study was conducted
      to investigate the purification efficiency of soil-plant systems with couchgrass
      (Elymus repens) and willows (Salix sp.) when intensively irrigated with run-off
      from an open sprinkling system at a Norway spruce (Picea abies) log yard. The
      purification efficiency was determined both at the field scale (couchgrass) and
      in 68-L lysimeters (couchgrass and willows). Groundwater in the field and
      drainage water from the lysimeters were analysed for Total Organic Carbon (TOC),
      distillable phenols, total P, and total N. Retention of TOC, phenols and P
      occurred but no difference between couchgrass and willows was observed. The
      system had better purification capacity at the field scale than in the
      lysimeters.

PMID- 15996803
TI  - Polycyclic aromatic hydrocarbons in suspended particulate matter and sediments
      from the Pearl River Estuary and adjacent coastal areas, China.
AB  - The spatial distribution, composition, and sources of polycyclic aromatic
      hydrocarbons (PAHs) in sediments and suspended particulate matter (SPM) from the
      Pearl River Estuary and adjacent coastal areas were examined. Total PAH
      concentrations varied from 189 to 637 ng/g in sediments and 422 to 1,850 ng/g in
      SPM. PAHs were dominated by 5,6-ring compounds in sediments and by 2,3-ring
      compounds in SPM samples. Assessment of PAH sources suggested that biomass and
      coal combustion is the major PAH source to the outer part of the estuary
      sediments and that petroleum combustion is the major PAH source to the inner part
      of estuary sediments. As for SPM samples, PAH isomer pair ratios indicated
      multiple (petroleum, petroleum combustion, and biomass and coal combustion) PAH
      sources, and significant temporal variations could exist for the sources of water
      column PAHs in the study area. The distribution of perylene in SPM samples
      indicated that the river was the dominant source of perylene in SPM and that
      perylene could be taken as an index to assess the contribution of river inflow to
      the total PAHs in SPM samples. The high concentration of perylene in the sediment
      was indicative of an in situ biogenic origin.

PMID- 15996804
TI  - Water quality dynamics and hydrology in nitrate loaded riparian zones in the
      Netherlands.
AB  - Riparian zones are known to function as buffers, reducing non-point source
      pollution from agricultural land to streams. In the Netherlands, riparian zones
      are subject to high nitrogen inputs. We combined hydrological, chemical and soil
      profile data with groundwater modelling to evaluate whether chronically N loaded
      riparian zones were still mitigating diffuse nitrate fluxes. Hydraulic parameters
      and water quality were monitored over 2 years in 50 piezometres in a forested and
      grassland riparian zone. Average nitrate loadings were high in the forested zone
      with 87 g NO(3)(-)-N m(-2) y(-1) and significantly lower in the grassland zone
      with 15 g NO(3)(-)-N m(-2) y(-1). Groundwater from a second aquifer diluted the
      nitrate loaded agricultural runoff. Biological N removal however occurred in both
      riparian zones, the grassland zone removed about 63% of the incoming nitrate
      load, whereas in the forested zone clear symptoms of saturation were visible and
      only 38% of the nitrate load was removed.

PMID- 15996805
TI  - Beliefs about treatment of mental health problems among Cambodian American
      children and parents.
AB  - Beliefs about treatment of mental health problems are a critical area for
      examination among immigrant and refugee populations. Data on treatment of child
      problems have been conspicuously absent from the literature. This study examines
      explanatory models of treatment among 40 second-generation Cambodian children
      aged 8-18 and their parents in the US. Comparisons of perceptions of intervention
      for an externalizing problem (gang-related behavior) and an internalizing problem
      (depression) are made in a group of children who have received mental health
      services, their parents, and a matched community sample. A significant
      interaction between respondent and group membership was present in the perception
      that these problems could be helped, and contrary to past findings among Asian
      Americans, both children and parents generally endorsed the use of mental health
      services. Data about actual experiences with mental health services are used to
      help explain the findings and suggest implications for treatment of Cambodian
      American youth.

PMID- 15996806
TI  - 2,4-Diaminotoluene (2,4-DAT)-induced DNA damage, DNA repair and micronucleus
      formation in the human hepatoma cell line HepG2.
AB  - 2,4-Diaminotoluene (2,4-DAT) is a widely used industrial intermediate and human
      exposure is possible in the dye and plastics industries. We investigated the
      genotoxicity of the environmental pollutant, 2,4-DAT, in human HepG2 cells using
      the unscheduled DNA synthesis (UDS) test, the micronucleus (MN) assay and single
      cell gel electrophoresis (SCGE). 2,4-DAT was first tested by the RNA synthesis
      inhibition test as a cytotoxicity assay: the IC(50) of 2,4-DAT was 5.2 mM after
      20 h of exposure. The compound had a genotoxic effect at concentrations from 1.45
      to 6.80 mM in both micronucleus and comet assays. In the micronucleus assay, the
      number of MN/1000 BNC was 3.5 times higher at a concentration of 6.80 mM 2,4-DAT
      than in the negative control. At the same concentration, DNA migration (SCGE)
      showed an Olive tail moment (OTM) of 3.56+/-0.45, as compared to 0.19+/-0.02 for
      the negative control. The UDS test detected genotoxic effects at lower
      concentrations than did the other assays (0.01-5 mM). The percentage of cells in
      repair increased in a concentration-dependent manner to a maximum of 57% at 1mM.
      At the highest concentration tested (5 mM), the NNG/cell score was 13.6+/-0.5
      whereas it was -2.7+/-0.5 for the negative control. These data, based on various
      endpoints, show a midly genotoxic effect of 2,4-DAT in the HepG2 cells and
      confirm that this cell line is a suitable model to study the toxic effects of
      aromatic amines.

PMID- 15996807
TI  - Phosphatidylinositol 3-kinase activator reduces motor neuronal cell death induced
      by G93A or A4V mutant SOD1 gene.
AB  - The primary pathogenic mechanism of amyotrophic lateral sclerosis (ALS) remains
      largely unclear. We recently observed that motoneuron cell death mediated by G93A
      or A4V mutant SOD1, causing familial ALS, was related with decrease of survival
      signals, such as phosphatidylinositol 3-kinase (PI3-K) and Akt, which play a
      pivotal role in neuronal survival. Using a G93A or A4V mutant SOD1 transfected
      VSC4.1 motoneuron cells (G93A or A4V cells, respectively), we presently
      investigated whether PI3-K activator could reduce mutant SOD1-mediated motoneuron
      cell death. To investigate the effect of PI3-K activator on viability of G93A and
      A4V cells, these cells were treated with 10, 50 or 100ng/ml PI3-K activator for
      24h and viability and intracellular signals, including Akt, glycogen synthase
      kinase-3 (GSK-3), heat shock transcription factor-1 (HSTF-1), cytosolic
      cytochrome c, caspase-3 and poly(ADP-ribose) polymerase (PARP), were compared
      with those without treatment (control). Compared with non-treated control G93A or
      A4V cells, the PI3-K activator treatment increased their viability by enhancing
      the survival signals, including pAkt, pGSK-3, and by inhibiting the death
      signals, including caspase-3 activation and PARP cleavage. These results suggest
      that PI3-K activator protects G93A or A4V cells from mutant SOD1-mediated
      motoneuron cell death by both activating survival signals and inactivating death
      signals.

PMID- 15996808
TI  - Molecular responses to xenoestrogens: mechanistic insights from toxicogenomics.
AB  - The xenoestrogen group of endocrine disruptors has the potential to cause
      reproductive and developmental effects through stimulation or disruption of sex
      steroid nuclear receptor signalling pathways. A more detailed understanding of
      the ways in which xenoestrogens interact with biological systems at the molecular
      level will provide a mechanistic basis for improved safety assessment. The recent
      sequencing of mammalian genomes has driven the development of toxicogenomic
      technologies, including microarray based gene expression profiling, which allow
      the expression levels of thousands of genes to be measured simultaneously. Since
      the cellular responses to xenoestrogens are predominantly mediated by estrogen
      receptors, which function as ligand-activated transcription factors to regulate
      gene expression, the application of toxicogenomics has great potential for
      providing insights into the molecular mechanisms of xenoestrogen action. A major
      challenge in applying toxicogenomics to the field of endocrine disruption is the
      need to define how xenoestrogen-induced changes in gene expression relate to
      conventional physiological and toxicological endpoints. Gene Ontology Mapping,
      Pathway Mapping and Phenotypic Anchoring of xenoestrogen-induced gene expression
      changes to cellular pathways and processes represent key steps in defining these
      relationships. Mechanistic insights into how xenoestrogens target specific genes
      and into the functional significance of xenoestrogen-induced alterations in gene
      expression can be further enhanced by combining transcript profiling with
      transgenic animal models or cell-based systems in which the estrogen receptor
      signalling pathways have been modified experimentally. This review illustrates
      how these toxicogenomic approaches are providing an unprecedented amount of
      mechanistic information on the molecular responses to xenoestrogens and how they
      are likely to impact on hazard and risk assessment.

PMID- 15996809
TI  - Dynamical behavior of lipid bilayer membranes for taste substances under random
      membrane-potential fluctuations.
AB  - The dynamical behavior of the lipid bilayer membranes was experimentally studied
      under superposition of random or periodic membrane-potential fluctuations. The
      analysis of the mutual information has revealed that, in less than 10 Hz of
      random fluctuations, each of the time series of the mutual information of the
      transmembrane current for the five chemical substances (taste substances) has its
      inherent pattern, but not in a periodic fluctuation. On the other hand, the
      analysis of the power spectrum of the frequency could not distinguish those five
      basic taste substances in both random and periodic fluctuations. We provide the
      new detection idea of chemical substances by random fluctuations.

PMID- 15996810
TI  - Physiology of ejaculation: emphasis on serotonergic control.
AB  - Ejaculation is constituted by two distinct phases, emission and expulsion.
      Orgasm, a feature perhaps unique in humans, is a cerebral process that occurs, in
      normal conditions, concomitantly to expulsion of semen. Normal antegrade
      ejaculation is a highly coordinated physiological process with emission and
      expulsion phases being under the control of autonomic and somatic nervous systems
      respectively. The central command of ejaculation is located at the thoracolumbar
      and lumbosacral levels of the spinal cord and is activated by stimuli from
      genital, mainly penile, origin although cerebral descending pathways exert both
      inhibitory and excitatory regulatory roles. Cerebral structures specifically
      activated during ejaculation form a tightly interconnected network comprising
      hypothalamic, diencephalic and pontine areas. A rational neurobiological approach
      has led to identify several neurotransmitters contributing to the ejaculatory
      process. Amongst them, serotonin (5-HT) has received strong experimental
      evidences indicating its inhibitory role in the central control of ejaculation.
      In particular, 5-HT1A cerebral autoreceptors but also spinal 5-HT1B and, in a
      lesser extent, 5-HT2C receptors have been shown to mediate the effects of 5-HT on
      ejaculation. Pharmacological strategies, especially those targeting serotonergic
      system, for the treatment of ejaculatory disorders in human will undoubtedly
      benefit from the application of basic and clinical research findings. In this
      perspective, the use of selective serotonin reuptake inhibitors (SSRIs) which
      basically increase the amount of central 5-HT and delay ejaculation in humans
      seems promising.

PMID- 15996811
TI  - A double-blind placebo-controlled study evaluating the onset of action of
      doxazosin gastrointestinal therapeutic system in the treatment of benign
      prostatic hyperplasia.
AB  - OBJECTIVE: To determine the onset of improvement in benign prostatic hyperplasia
      symptoms in patients after treatment with doxazosin gastrointestinal therapeutic
      system (DOX GITS) versus placebo. METHODS: In this prospective, randomized,
      double-blind, placebo-controlled trial, baseline values, including International
      Prostate Symptom Score (IPSS) and maximum urine flow rate (Q(max)), were
      determined following a 2-week placebo run-in. Patients received DOX GITS 4 mg/d
      (n = 108) or placebo (n = 105) for 14 days. IPSS was measured on Days 3, 7, and
      14; Q(max) on Days 1, 3, 7, and 14; and the patients' perception of improvement
      was measured on Days 1 and 2 in the evening at home and in the office on Day 14.
      RESULTS: Significantly more patients treated with DOX GITS than placebo perceived
      improvement after Day 1 (60.6% vs. 41.9%) through Day 14 (84.3% vs. 64.1%). On
      Day 1, improvement in Q(max) with DOX GITS was not significantly different
      compared with placebo. On Day 3 of the trial (1) IPSS improvement was
      significantly greater with DOX GITS than with placebo; (2) proportion of patients
      with > or =30% improvement in IPSS was significantly greater with DOX GITS
      (49.5%) than placebo (28.4%) and remained so through Day 14; (3) improvement in
      Q(max) was significantly greater with DOX GITS (3.7 mL/s) than placebo (1.9 mL/s)
      and remained so through Day 14; (4) proportion of patients with > or =3 mL/s
      increase in Q(max) was statistically greater with DOX GITS (54.4%) versus placebo
      (30.8%) and remained so through Day 14. CONCLUSIONS: DOX GITS significantly
      improved IPSS and Q(max) by Day 3 of treatment, and these changes were maintained
      through Day 14. More patients receiving DOX GITS than placebo perceived
      improvement in symptoms as early as Day 1.

PMID- 15996812
TI  - DNA damaging drugs-induced down-regulation of Bcl-2 is essential for induction of
      apoptosis in high-risk HPV-positive HEp-2 and KB cells.
AB  - DNA damaging chemotherapeutic agents like carboplatin (Carb) and 5-fluorouracil
      (5-FU), whose effects are mediated through diverse intracellular targets, induce
      apoptosis in various cancer cells including human papillomavirus (HPV) positive
      HEp-2 and KB cells. The present work reports the involvement of Bcl-2 in response
      to the exposure of HEp-2 and KB cells to Carb or 5-FU. We demonstrate that both
      these drugs are potent inducers of apoptosis. Apoptosis was preceded by decrease
      in Bcl-2 protein level accompanied by caspase-9 activation and poly(ADP-ribose)
      polymerase (PARP) cleavage without altering Bax expression. Further analysis
      revealed down-regulation of Bcl-2 mRNA as well as protein in drugs treated cells.
      Ectopic expression of Bcl-2 protected cells against drugs mediated DNA damage
      induced apoptosis. Overall, data indicates that genotoxic stress leads to down
      regulation of Bcl-2 in HEp-2 and KB cells, which plays a decisive role in the
      outcome of stress in these cells.

PMID- 15996813
TI  - Removal of dyes using immobilized titanium dioxide illuminated by fluorescent
      lamps.
AB  - The photodegradation of various dyes in aqueous solution was studied. Experiments
      were carried out using glass coated titanium dioxide thin film as photocatalyst.
      Photodegradation processes of methylene blue (MB), methyl orange (MO), indigo
      carmine (IC), chicago sky blue 6B (CSB), and mixed dye (MD, mixture of the four
      mentioned single dye) were reported. As each photodegradation system is pH
      dependent, the photodegradation experiment was carried out in each dye
      photodegradation reactive pH range at approximately 28 degrees C. The dyes
      removal efficiency was studied and compared using UV-vis spectrophotometer
      analysis. The total removal of each dye was: methylene blue (90.3%), methyl
      orange (98.5%), indigo carmine (92.4%), chicago sky blue 6B (60.3%), and mixed
      dyes (70.1%), respectively. The characteristic of the photocatalyst was
      investigated using X-ray diffractometer (XRD). The amount of each dye
      intermediate produced in the photodegradation process was also determined with
      the help of total organic carbon (TOC) analysis.

PMID- 15996814
TI  - Removal of nickel from aqueous solutions using crab shells.
AB  - Partially converted crab shell waste, which contains chitosan, was used to remove
      nickel from water. The chelating ability of chitosan makes it an excellent
      adsorbent for removing pollutants. Advantages of chitosan in crab shells include
      availability, low cost, and high biocompatibility. The metal uptake by partially
      converted crab shell waste was successful and rapid. The sorption occurred
      primarily within 5 min. The sorption mechanism appears to be quite complicated
      and cannot be adequately described by either the Langmuir or Freundlich theories.
      Various anions, including chloride, bromide, fluoride, acetate, sulfate, nitrate,
      and phosphate, were found to have a very small effect on the capacity of the crab
      shells for uptake of nickel. The effect of pH was also found not to be prominent.

PMID- 15996815
TI  - Equilibrium biosorption isotherm for lead ion on chaff.
AB  - A new adsorbent system for removing lead ion from aqueous solutions has been
      investigated. This new adsorbent is cereal chaff, an agriculture product in
      middle-west region in China. Variables of the system include biosorption time,
      chaff dose and solution temperature. The experimental results were fitted to the
      Langmuir, Freundlich, Koble-Corrigan and Temkin model isotherms to obtain the
      characteristic parameters of each model. Both the Langmuir and Koble-Corrigan
      isotherms were found to best represent the measured biosorption data. According
      to the evaluation using the Langmuir equation, the maximum biosorption capacities
      of lead ion onto chaff was 12.5 mgg(-1) at 293 K. Using the thermodynamic
      equilibrium coefficients obtained at different temperatures, various
      thermodynamic parameters, such as DeltaG(0), DeltaH(0) and DeltaS(0), have been
      calculated. The thermodynamics of lead ion-chaff system indicates spontaneous and
      exothermic process. It was concluded that an increase in temperature result in a
      lower metal loading per unit weight of the chaff.

PMID- 15996816
TI  - Studies on adsorption, desorption and biodegradation of pentachlorophenol by the
      anaerobic granular sludge in an upflow anaerobic sludge blanket (UASB) reactor.
AB  - PCP-degrading anaerobic granular sludge could be formed in an upflow anaerobic
      sludge blanket (UASB) reactor that was seeded with anaerobic sludge acclimated to
      chlorophenol. When hydraulic retention time (HRT) was 20-22 h and PCP loading
      rate was 200-220 mgL(-1)d(-1), the wastewater containing 170-180 mgL(-1) PCP
      could be treated effectively in UASB reactor, and PCP removal rate reached up to
      99.5%. PCP adsorption and desorption by anaerobic granular sludge follow
      Freundlich isothermal equation and part of adsorption capacity was not
      reversible. And the isothermal equation could well describe the variation law of
      PCP adsorption and desorption by anaerobic granular sludge. The results indicated
      that the principal removal mechanism of PCP was biodegradation by anaerobic
      granular sludge, but not adsorption or volatilization.

PMID- 15996817
TI  - Pilot scale annular plug flow photoreactor by UV/H2O2 for the decolorization of
      azo dye wastewater.
AB  - A pilot scale annular plug flow photoreactor with thin gap size, which combines
      with UV irradiation and hydrogen peroxide, was employed to deal with colored
      dyeing wastewater treatment. In the experiment, a mono-azo dye acid orange 10 was
      the target compound. The experimental parameters such as flow rate, hydrogen
      peroxide dosage, UV input power, pH and dye initial concentrations in a pilot
      scale photoreactor with flow rate of 9.32 m3day(-1) were investigated.
      Ultimately, the degradation rates were calculated and compared with a 100-l batch
      reactor. In our plug flow photoreactor design, the degradation rate of acid
      orange 10 was 233 times higher than that of 100-l annular batch reactor with same
      UV light source. The residence time needed for 99% decolorizing of 100 l of 20
      mgl(-1) acid orange 10 wastewater was 26.9 min for the thin gap plug flow reactor
      and was far shorter than that of batch reactor needed.

PMID- 15996818
TI  - Application of artificial neural networks for modeling of the treatment of
      wastewater contaminated with methyl tert-butyl ether (MTBE) by UV/H2O2 process.
AB  - During the last two decades, methyl tert-butyl ether (MTBE) has been widely used
      as an additive to gasoline (up to 15%) both to increase the octane number and as
      a fuel oxygenate to improve air quality by reducing the level of carbon monoxide
      in vehicle exhausts. The present work mainly deals with photooxidative
      degradation of MTBE in the presence of H2O2 under UV light illumination (30W). We
      studied the influence of the basic operational parameters such as initial
      concentration of H2O2 and irradiation time on the photodegradation of MTBE. The
      oxidation rate of MTBE was low when the photolysis was carried out in the absence
      of H2O2 and it was negligible in the absence of UV light. The addition of proper
      amount of hydrogen peroxide improved the degradation, while the excess hydrogen
      peroxide could quench the formation of hydroxyl radicals (OH). The semi-log plot
      of MTBE concentration versus time was linear, suggesting a first order reaction.
      Therefore, the treatment efficiency was evaluated by figure-of-merit electrical
      energy per order (E(Eo)). Our results showed that MTBE could be treated easily
      and effectively with the UV/H2O2 process with E(Eo) value 80 kWh/m3/order. The
      proposed model based on artificial neural network (ANN) could predict the MTBE
      concentration during irradiation time in optimized conditions. A comparison
      between the predicted results of the designed ANN model and experimental data was
      also conducted.

PMID- 15996819
TI  - Nonlinear imaging using annular dark field TEM.
AB  - Annular dark field TEM images exhibit a dominant mass-thickness contrast that can
      be quantified to extract single atom scattering cross sections. On top of this
      incoherent background, additional lattice fringes appear with a nonlinear
      information limit of 1.2A at 150 kV. The formation of these fringes is described
      by coherent nonlinear imaging theory and good agreement is found between
      experimental and simulated images. Calculations furthermore predict that the use
      of aberration corrected microscopes will improve the image quality dramatically.

PMID- 15996820
TI  - Calculations of HREM image intensity using Monte Carlo integration.
AB  - We have developed a numerical approach for the accurate and efficient calculation
      of HREM image intensity formed using a partially coherent source. The approach is
      based on Monte Carlo integration, and is suitable for use in general image
      restoration methods using a series of images. The accuracy of this approach is
      compared with calculations based on the transmission cross coefficient (TCC) for
      strong scattering objects, as a function of the number of sampling points,
      defocus, atomic number and specimen thickness. Its efficiency is compared with
      that of exact TCC calculations based on equally-spaced sampling of the beam
      divergence and focal spread distributions. The results indicate that the Monte
      Carlo approach is particularly advantageous for nonlinear image restoration
      algorithms.

PMID- 15996821
TI  - Energy-filtered electron-diffracted beam holography.
AB  - A method of energy-filtered electron holography is described where any two
      electron-diffracted beams can be interfered using an electron biprism. A Gatan
      image filter is used to select the energy loss of the electrons produced in the
      holograms. Gallium arsenide is used as the TEM specimen. This method of
      microscopy confirms that fringes extending beyond a limiting aperture were due to
      inelastically scattered electrons and specifically electrons scattered from the
      bulk plasmon. The degree of coherence of the zero-loss and energy-loss electrons
      were high and measured to be approximately 0.3, which was maintained even for the
      high energy-loss electrons up to 100 eV. Future systematic studies using this
      method should help understand the Stobbs factor and contribute to the development
      of quantitative high-resolution electron microscopy.

PMID- 15996822
TI  - Persistence of reactivity against the 45 k Da glycoprotein in late trichinellosis
      patients.
AB  - Over the years, the opinions of clinicians on the existence of the so-called
      chronic trichinellosis or late sequelae of infection have differed. However, the
      persistence of a humoral immune response against Trichinella in these late-stage
      patients has been confirmed using specific tests such as the competitive
      inhibition assay (CIA). We evaluated sera from late-stage trichinellosis patients
      (2--8 years from acute infection), for their reactivity against Trichinella
      spiralis antigens. The following tests were carried out: (i) indirect
      immunofluorescence assay (IFA), performed on muscle sections from mice, 30 days
      following synchronous infection by intramuscular injection with T. spiralis
      newborn larvae (NBL); (ii) enzyme immunoassay, employing a synthetic beta
      tyvelose antigen conjugated to bovine serum albumin (BSA-Ag); and (iii) western
      blot (WB) with both an "in house" kit and a commercial kit. The results of IFA
      obtained by confocal laser microscopy showed that sera reacted against both
      surface and internal structures of L(1) larvae but at varying levels. Employing
      the synthetic antigen, EIA showed that 50% of sera tested were positive for the
      presence of specific antibodies against beta-tyvelose. By WB, all sera were
      reactive with the 45 k Da glycoprotein (45 gp). These data suggest that
      reactivity against the beta-tyvelosylated 45 gp persists even in very late stages
      of human trichinellosis.

PMID- 15996823
TI  - Adaptative metabolic response of human colonic epithelial cells to the adverse
      effects of the luminal compound sulfide.
AB  - Hydrogen sulfide (H(2)S), a bacterial metabolite present in the lumen of the
      large intestine, is able to exert deleterious effects on the colonic epithelium.
      The mechanisms involved are still poorly understood, the reported effect of
      sulfide being its capacity to reduce n-butyrate beta-oxidation in colonocytes. In
      this work, we studied both the acute effect of the sodium salt of H(2)S on human
      colonic epithelial cell metabolism and the adaptative response of these cells to
      the pre-treatment with this agent. Using the human colon carcinoma epithelial HT
      29 Glc(-/+) cell model, we found that the acute effect of millimolar
      concentrations of NaHS was to inhibit l-glutamine, n-butyrate and acetate
      oxidation in a dose-dependent manner. Using micromolar concentrations of NaHS, a
      comparable effect but largely reversible was observed for O(2) consumption and
      cytochrome c oxidase activity. Pre-treatment with 1 mM NaHS induced several
      adaptative responses. Firstly, increased lactate release and decreased cellular
      oxygen consumption evidenced a Pasteur-like effect which only partly compensated
      for the altered mitochondrial ATP production. Thus, a decrease in the
      proliferation rate with a constant adenylate charge was observed. Secondly, in
      these pre-treated cells, NaHS induced a hypoxia-like effect on cytochrome c
      oxidase subunits I and II which were decreased. Thirdly, a mild uncoupling of
      mitochondrial respiration possibly resulting from an increase of UCP 2 protein
      was observed. The NaHS antimitotic activity was not due to cellular apoptosis
      and/or necrosis but to a proportional slowdown in all cell cycle phases. These
      results are compatible with a metabolic adaptative response of the HT-29 colonic
      epithelial cells to sulfide-induced O(2) consumption reduction which, through the
      maintenance of a constant energetic load and an increased mitochondrial proton
      leak, would participate in the preservation of cellular viability.

PMID- 15996824
TI  - Membranous osteogenesis system modeled with KUSA-A1 mature osteoblasts.
AB  - Several stromal cells were established from murine bone marrow cultures. One of
      the KUSA subclones, KUSA-A1 cells, displays osteogenic characteristics in vitro
      and in vivo. The calcium deposition, osteocalcin release, and parathyroid hormone
      (PTH) responsiveness of KUSA-A1 cells indicate that they are mature osteoblasts
      or osteocytes. Bone had formed in subcutaneous tissue 1 week after subcutaneous
      injection of cells into immunodeficient mice. The osteogenesis by KUSA-A1 was not
      mediated by chondrogenesis and thus was considered to be membranous ossification.
      These unique characteristics of KUSA-A1 cells provide an opportunity to analyze
      the process of membranous ossification in detail.

PMID- 15996825
TI  - Sex and ovarian steroids modulate brain-derived neurotrophic factor (BDNF)
      protein levels in rat hippocampus under stressful and non-stressful conditions.
AB  - Abnormal levels of brain-derived neurotrophic factor (BDNF) are associated with
      major depression, a disorder with a higher incidence in women than men. Stress
      affects BDNF levels in various brain regions and thus, a heightened stress
      response in females could contribute to the development of depression. As well,
      ovarian hormones directly affect brain levels of BDNF mRNA and protein. Two
      experiments were performed to investigate the effects of stress and sex and
      gonadal hormones on BDNF protein levels in CA1, CA3, and dentate gyrus (DG)
      subregions of the hippocampus. In the first experiment, male and female Sprague
      Dawley rats were subjected to one hour of restraint stress or control handling
      prior to sacrifice. In the second experiment, fifty-one female rats were
      ovariectomized and separated into stress and control conditions, as described for
      the first experiment. Stressed and handled groups received a single injection of
      estrogen (E; 53h prior to stress), estrogen and progesterone (EP; E given at 53h
      and P given 5h prior to stress), or vehicle (OVX). In both experiments BDNF
      protein was quantified using an enzyme-linked immunosorbent enzyme assay (ELISA)
      in micropunches of hippocampus. Gonadally intact females had significantly higher
      levels of BDNF in CA3, but significantly lower levels in DG, relative to males.
      In CA3, stress significantly decreased BDNF in both males and females. In DG of
      ovariectomized female rats, the effects of stress were significantly different
      following EP vs. vehicle treatment. Thus, stress increased BDNF levels in EP
      treated rats but decreased BDNF levels in vehicle-treated rats. Reduced trophic
      support in DG in the presence of estrogen and progesterone could jeopardize
      neurogenesis and under certain conditions could be a contributing factor to the
      hippocampal atrophy associated with stress-induced affective disorders. These
      results emphasize the need to consider sex, gonadal steroids, and hippocampal
      subregion when examining the effects of stress on the brain.

PMID- 15996826
TI  - Stress and cigarette smoking in Korean men with diabetes.
AB  - The purpose of the study was to investigate the level of stress and cigarette
      smoking behaviors in Korean men with diabetes and to exam the relationships among
      them. Data were collected using the questionnaire including background
      characteristics, modified Brief Encounter Psychosocial Instrument (BEPSI) and the
      Fagerstrom Tolerance Questionnaire (FTQ). 37% of the participants were current
      smokers with a mean of 4.22 FTQ score. 22% among the current smokers had a
      nicotine dependency. 43.1% indicated they were considering quitting smoking
      within 6 months. The level of stress was not associated with the amount of
      smoking. However, the level of stress was associated with nicotine dependency.
      There were no significant differences between the smoking cessation stage and
      stress. In conclusion, the prevalence of smoking among Korean men with diabetes
      is high. The large proportion of smokers in the contemplation and preparation
      stages should be supported by the need for stage-matched interventions targeting
      this special group of smokers.

PMID- 15996827
TI  - Feasibility of an email-based electronic screening and brief intervention (e-SBI)
      to college students in Sweden.
AB  - An email-based electronic screening and brief intervention (e-SBI) with
      personalized normative feedback on alcohol habits was offered to all 3,875 second
      term students at Linkoping University, Sweden. The students received an email
      with a link to a computerized alcohol habit test and were offered personalized
      feedback directly on the computer screen. The students evaluated the test and
      were asked to state whether they were going to consider changing or actually
      change their alcohol habits. The response rate was 44%, with 742 female and 843
      male students participating. The students displayed a strong gender difference in
      drinking pattern. A three-fold higher percentage of males than females were risky
      drinkers with regard to a high average weekly volume consumption. The gender
      differences were less pronounced regarding heavy episodic drinking that was
      reported by 51% of the females and 70.5% of the males. The email-based
      computerized normative feedback was appreciated by the students and one-third of
      the females and one-fifth of the males believed that they would benefit from the
      normative feedback; 8% of the females and 3% of the males believed that they
      would actually change their habits after the feedback. Students with a risky
      drinking pattern, previous experiences of blackouts, being dissatisfied with
      their current drinking and students that had considered to change their habits
      before the e-SBI, yielded a stronger motivation to change their drinking after
      having performed the intervention compared to students without such
      characteristics. The e-SBI with normative feedback was simple to administer and
      has the potential to be used repeatedly and on a large scale with minimum effort
      in terms of cost and time.

PMID- 15996828
TI  - Therapeutic potentials of unicellular green alga Chlorella in advanced glycation
      end product (AGE)-related disorders.
AB  - Reducing sugars can react non-enzymatically with amino groups of protein to form
      Amadori products. These early glycation products undergo further complex reaction
      such as rearrangement, dehydration, and condensation to become irreversibly cross
      linked, heterogeneous fluorescent derivatives, termed advanced glycation end
      products (AGEs). The formation and accumulation of AGEs in various tissues has
      been known to progress at an accelerated rate under hyperglycemic conditions in
      diabetes. Recent understanding of this process has revealed that AGEs have been
      implicated in the development of many of the pathological sequelae of diabetes
      and aging, such as atherosclerosis and diabetic microangiopathy. Furthermore,
      recently, AGE-their receptor (RAGE) interaction was also involved in
      neurodegenerative diseases, melanoma growth, expansion and metastasis. These
      observations suggest that blockade of AGE formation may be a novel promising
      target for therapeutic intervention in these devastating AGE-related disorders.
      We have recently found that unicellular green alga Chlorella inhibited the
      formation of AGEs in vitro. Since several lines of evidence have shown anti
      atherogenic effects of Chlorella on animal models, we hypothesize here that the
      beneficial aspects of Chlorella on atherosclerosis could be ascribed, at least in
      part, to its AGE inhibitory property and that Chlorella may have therapeutic
      potentials in treatment of patients with other AGE-related disorders such as
      diabetic microangiopathy and Alzheimer's disease. In this paper, we would like to
      propose the possible ways of testing our hypotheses. Does daily intake of
      Chlorella reduce the risk of the incidence and progression of diabetic vascular
      complications including atherosclerosis? Does Chlorella treatment prevent the
      development of Alzheimer's disease and/or improve the cognitive impairment of
      patients with this disorder? If the answers are yes, are plasma or tissue levels
      of AGE in these patients actually suppressed by Chlorella treatment? And, does
      the extent of the AGE reduction by Chlorella predict the beneficial effects of
      Chlorella on these disorders? These prospective studies will provide further
      valuable information whether blockade by Chlorella of the AGE formation could be
      clinically relevant.

PMID- 15996829
TI  - Plasticity imbalance in mental disorders the neuroscience of psychiatry:
      implications for diagnosis and research.
AB  - In 1895 Freud tried to explain mental disorders using the neurophysiological
      knowledge of his time. He soon abandoned this attempt realizing it was immature
      considering the neuroscientific knowledge available to him. For the rest of his
      career he limited himself to psychological formulations. Along the same lines,
      lacking etiology for mental disorders, the diagnostic system of psychiatry is
      exclusively descriptive. The need for a brain related diagnosis of mental
      disorders is important for developing better treatments and more reliable
      diagnosis. Today with the development of neuroscience it is time to go back to
      Freud's initial attempts and explain mental disorders as altered neuronal
      organizations in the brain. The neural network level is chosen as the relevant
      description level for mental functions. Plasticity is chosen as a general concept
      for neuronal dynamics explaining neuropathology of psychiatric disorders.
      Plasticity is divided according to timescales into "fast plasticity," "slow
      plasticity" and "stable plasticity". It is proposed that normal mental functions
      require optimal balance among all the plasticity timescales. Mental disorders
      arise when such balance is disturbed, thus mental disorders could be reformulated
      as deficiencies of the different plasticity processes. Changes in coherence
      synchrony and phase-locking membrane potentials in cortically spread neuronal
      ensembles are all expressions of fast plasticity. Synaptogenic and neurogenic
      processes, such as brain derived neurotrophic factor-dependent processes, are
      defined as slow plasticity. Finally those synaptic and neuronal pathways that
      consolidated into long lasting circuits are referred to as stable plasticity.
      With the aid of a neural network model simulating the plasticity imbalance, a
      mathematical formulation could be realized for mental disorders. Once achieved
      this mathematical formulation could form a guiding framework for interpreting
      brain-imaging data collected from psychiatric patients. Such a model is realized
      using interconnected "modules" each simulating the relevant plasticity dynamics
      relevant for the model. Diagnosing plasticity imbalance has some advantages over
      current descriptive psychiatric diagnosis. It is brain-related thus less
      stigmatising in the sense that mental disorders are brain disorders and not
      "person" disorders. The diagnostic system is much more flexible allowing for a
      high degree of variations and combinations in the description of the disorders
      thus naturally accounting for comorbidities. Most importantly, this diagnostic
      model is brain-related offering research targets for intervention and a
      theoretical framework guiding such interventions.

PMID- 15996830
TI  - Incidence of plasma cell dyscrasia as a second primary malignancy may be low in
      postmenopausal breast cancer survivors treated with selective estrogen receptor
      modulator or aromatase inhibitor.

PMID- 15996831
TI  - The plasmodial apicoplast was retained under evolutionary selective pressure to
      assuage blood stage oxidative stress.
AB  - Malaria, the clinical disease resulting from infection with Plasmodium, has
      haunted mankind with illness and death for thousands of years. As Plasmodia's
      ancient ancestor evolved from a mixotroph to an intracellular parasite, subsiding
      on amino acids obtained from hemoglobin, it encountered increased oxidative
      stress. To compensate for this oxidative stress, Plasmodia reduced its own
      production of reactive oxygen species by becoming largely fermentative and
      adapted novel methods to assuage oxidative injury. One such method appears to
      have been accomplished through the acquisition, retention and exploitation of an
      ancient red algal endosymbiote, now denoted the apicoplast. The apicoplast,
      located in close proximity to mitochondria, appears to synthesize the potent
      antioxidant lipoic acid. Lipoic acid may be utilized by Plasmodium as an
      antioxidant, a shuttle for reducing potentials and as a mitochondrial cofactor.
      Inhibition or alteration of the apicoplast leads to a curious phenomena known as
      "delayed death", whereby parasites die not in the present generation but in the
      ensuing one. Apicoplast inhibition may produce lipoic acid "starvation",
      increasing oxidative stress/mitochondrial injury during the subsequent asexual
      reproductive cycle. Collectively, data available to date indicate that the
      apicoplast was retained as an obligate endosymbiote, under evolutionary selective
      pressure, to assuage oxidative stress and plays a critical role in maintaining
      parasite viability during the Plasmodial shizont blood stage.

PMID- 15996832
TI  - One of possible mechanisms on no-reflow in post-percutaneous coronary
      intervention: coronary shock due to micro-coronary stunning.

PMID- 15996833
TI  - Parental care and sexual interactions in Mongolian gerbils (Meriones
      unguiculatus) during the postpartum estrus.
AB  - The behavior of male and female Mongolian gerbils was continuously video-recorded
      from 24 h before the parturition to the end of postpartum estrus. We noted that
      the mean interval between the delivery of the last pup and the first mounting was
      13 h and 32 min. Over the whole duration of the postpartum estrus (7 h and 41+/
      57 min), females spent significantly more time in crouching over, pup licking,
      nest building and "digging" activities, and were more recipient of allogrooming
      than males. Maternal pup retrievals were not very frequent (14.0+/-5.6 episodes),
      but males never retrieved pups nor exhibited a full sequence of nest building
      activity. Males spent a longer mean time in bodily interactions with females, as
      compared to the time they spent with pups, and engaged in intense copulatory
      activity (592.8+/-40.5 mounts or 1 episode per 46.7s); even during the delivery
      process males attempted to force copulation, but females rejected mounting in all
      cases. We conclude that females exhibited higher levels of parental care than
      males, and our findings suggest that males compete with pups in attracting the
      female's attention, since they actively disrupt maternal care or persistently
      persecute the female in order to copulate.

PMID- 15996834
TI  - Cloning and expression of the amphibian homologue of the human PKD1 gene.
AB  - PKD1 is the gene responsible for autosomal dominant polycystic kidney disease
      (ADPKD) type 1 in humans. The PKD1 gene product is likely to be a calcium channel
      regulator. In this paper, we describe the isolation and characterization of the
      Xenopus homologue of the human PKD1 gene. We isolated and cloned genomic
      fragments corresponding to the amphibian homologue of PKD1 from a BAC library,
      and after sequencing the clones, we designed primers for the amplification of the
      transcript and sequenced 10 kb of ORF. The sequence of the putative protein
      clearly demonstrated that this gene is the homologue of human PKD1. Analysis of
      the tissue expression patterns of xPKD1 demonstrated a high level of expression
      in the kidney. A similar analysis in developing embryos and in an in vitro
      nephrogenic system suggests that xPKD1 is associated with, and probably involved
      in, the development of the amphibian pronephros.

PMID- 15996835
TI  - Changes in fractal features of fetal heart rate during pregnancy.
AB  - OBJECTIVE: Our objective was to examine whether heart rate time series of healthy
      normal fetuses possess fractal properties and, if so, to determine whether
      consistent changes in fractal features according to gestational age exist. DESIGN
      OF THE STUDY: One hundred nineteen fetal heart rate (FHR) recordings in 55
      singleton pregnancies between the 22nd and 41st weeks were analyzed. Fractal
      analysis developed by Higuchi was performed. Changes of fractal dimension were
      examined according to gestational age. RESULTS: Two characteristic scaling
      regions were present in each FHR trace. The fractal dimension defined within 500
      ms to 5 s (D(S); median 1.396, range 1.273-1.642) was lower than that defined
      longer than 30 s (D(L); median 1.933, range 1.492-2.049) in every case. These two
      values were significantly different (p<0.001). There was a statistically
      significant difference in the values of D(S) between (22-29 weeks, mean 1.323),
      (30-33 weeks, mean 1.443) (p=0.004), (34-35 weeks, mean 1.418) (p=0.002), (36
      weeks, mean 1.409) (p=0.030), (37-38 weeks, mean 1.394) (p=0.006), and (40-41
      weeks, mean 1.452) (p=0.001), respectively. D(S) values between (40-41 weeks),
      (37-38 weeks) (p=0.012), and (39 weeks, mean 1.369) (p=0.030), respectively, were
      also significantly different. The values of D(L) decreased from 22-39 weeks
      (median 1.941) to 40-41 weeks (median 1.891) (p=0.008). CONCLUSIONS: Two distinct
      fractal structures within the FHR variation were identified. Fractal features of
      heart rate of healthy normal fetuses change significantly during pregnancy
      period. Fractal analysis may be useful for evaluating FHR variation.

PMID- 15996836
TI  - Radiological evaluation of bone growth in neonates born at gestational ages
      between 26 and 41 weeks: cross-sectional study.
AB  - The length of the ossified part of the long bones of the upper (humerus) and
      lower limb (femur) as well as the axial length (that is, height) of the vertebral
      body of L1 were measured on a plain supine radiograph in 347 newborn babies (228
      males, 119 females) with the gestational age (GA) from 26 to 41 weeks. All were
      admitted to the neonatal intensive care unit. Reasons for admission included
      hyaline membrane disease, meconium aspiration syndrome, neonatal asphyxia or
      transient tachypnea of the newborn. Patients with abnormal growth, gross
      anomalies, or who were the products of multiple births were excluded. The average
      weekly increment in the height of L1 for male infants born at GA varying from 26
      to 41 weeks was 0.23 mm, for the humerus 1.82 mm and for the femur 2.35 mm. The
      corresponding data for females was 0.20 mm, 1.54 mm and 2.30 mm. The ratio of the
      height of L1 to body length progressively increased between 26 to 41 weeks. A
      growth spurt in L1 was noted for both sexes at 34 weeks of GA. Long bone growth
      was similar in male and female infants born before 36 weeks. However, the ratio
      of femur to body length in males increased after 36 weeks. The ratio of humerus
      to body length remained constant over the entire range of GA.

PMID- 15996837
TI  - A case study of acute human chlorpyrifos poisoning: novel aspects on metabolism
      and toxicokinetics derived from liquid chromatography-tandem mass spectrometry
      analysis of urine samples.
AB  - The metabolic fate of the organophosphorothioate-type insecticide chlorpyrifos
      (CP) in an acutely intoxicated 59 years old female was investigated by liquid
      chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS)
      analysis of urine samples. Fifteen metabolites of CP and its bioactivated
      intermediate chlorpyrifos-oxon (CPO), respectively, of which only three have been
      described in man so far, were identified on the basis of characteristic MS/MS
      transitions, precursor/product ion and/or neutral loss scans, chlorine isotopomer
      patterns, and partly by synthesis of reference compounds and subsequent structure
      confirmation. Three distinct biotransformation routes of CP are proposed: (1)
      cleavage reactions at the aromatic phosphoester bond, (2) cleavage reactions at
      the alkyl phosphoester bonds, and (3) glutathione (GSH) dependent nucleophilic
      substitution of the 6-chlorine at the aromatic moiety. Route (2) has not been
      reported in humans before and (3) is a hitherto completely unknown scheme of CP
      metabolism. Urinary markers of the latter were chiefly cysteine S-conjugates of
      mono-dechlorinated CP, CPO, mono-O-deethyl CP, and mono-O-deethyl CPO as well as
      the 6-mercapturic acid conjugate of 3,5-dichloro-2-pyridinol. The presence of 3,5
      dichloro-6-methylthio-2-pyridinol as well as its O-glucuronide suggests further a
      cysteine S-conjugate beta-lyase mediated degradation. In addition to the
      qualitative LC-MS/MS screening the renal elimination profiles of the primary
      products of scheme (1), i.e. diethyl thiophosphate (DETP), diethyl phosphate
      (DEP), and 3,5,6-trichloro-2-pyridinol (TCP), were monitored over 14 days (n=21).
      A biphasic first-order excretion mechanism with half-lives of 21.5h (initial fast
      excretion phase) and 119.5h (terminal phase) for the sum of free DETP and DEP was
      found. TCP was hardly eliminated in its free form (O-glucuronide identified as
      phase II conjugate) and half-lives calculated for the total amount of TCP (acidic
      hydrolysis of urine samples) were 40.8 and 150.7h. The present study gives a more
      detailed view on the biotransformation of CP and together with the obtained
      kinetic data adds novel aspects to the limited knowledge of human metabolism of
      this xenobiotic, in particular at high dosage.

PMID- 15996838
TI  - Preparation and characterization of nanocrystals for solubility and dissolution
      rate enhancement of nifedipine.
AB  - Poorly water-soluble drugs such as nifedipine (NIF) (approximately 20 microg/ml)
      offer challenging problems in drug formulation as poor solubility is generally
      associated to poor dissolution characteristics and thus to poor oral
      bioavailability. In order to enhance these characteristics, preparation of
      nifedipine nanoparticles has been achieved using high pressure homogenization.
      The homogenization procedure has first been optimized in regard to particle size
      and size distribution. Nanoparticles were characterized in terms of size,
      morphology and redispersion characteristics following water-removal. Saturation
      solubility and dissolution characteristics were investigated and compared to the
      un-milled commercial NIF to verify the theoretical hypothesis on the benefit of
      increased surface area. Crystalline state evaluation before and following
      particle size reduction was also conducted through differential scanning
      calorimetry (DSC) and powder X-ray diffraction (PXRD) to denote eventual
      transformation to amorphous state during the homogenization process. Through this
      study, it has been shown that initial crystalline state is maintained following
      particle size reduction and that the dissolution characteristics of nifedipine
      nanoparticles were significantly increased in regards to the commercial product.
      The method being simple and easily scaled up, this approach should have a general
      applicability to many poorly water-soluble drug entities.

PMID- 15996839
TI  - pH-dependent association of SN-38 with lipid bilayers of a novel liposomal
      formulation.
AB  - The aim of this study was to determine the location of SN-38 molecules in a
      liposomal formulation as a function of pH. Steady-state fluorescence polarization
      anisotropy and gel filtration studies of blank (placebo) liposomes, liposomes
      containing SN-38 and SN-38 solutions (in some cases suspensions) were conducted
      before lyophilization and after re-hydration at different pH conditions. SN-38, l
      (4-trimethylammoniumphenyl)-6-phenyl-l,3,5-hexatriene p-toluenesulfonate (TMA
      DPH), N-((4-(6-phenyl-l,3,5-hexatrienyl)phenyl)propyl)trimethylammonium p
      toluenesulfonate (TMAP-DPH) and l,6-diphenyl-l,3,5-hexatriene (DPH) were used as
      fluoroprobes in the polarization anisotropy measurements. The localization of SN
      38 was governed by the degree of hydrophobicity of the drug molecules. At high
      pH, SN-38 is in its inactive, hydrophilic form and partitioned into the water
      phase of the liposome suspensions. In lyophilized LE-SN38 liposomes re-hydrated
      with low pH buffer, SN-38 was found at the water-lipid interface of the bilayer.

PMID- 15996840
TI  - Functional organization of the forebrain auditory centres of the European
      starling: a study based on natural sounds.
AB  - The field L complex is thought to be the highest auditory centre and the input in
      the song vocal nuclei. Different anatomical and functional subdivisions have been
      described in field L. Auditory neurons of field L are well activated by natural
      sounds and especially by species-specific sounds. A complex sound coding appears
      to exist in field L. However, until now, the spatial organization of the
      different functional subdivisions has been described only using artificial
      sounds. Here, we investigated the spatial distribution of neuronal responses in
      field L to species-specific songs. Starlings seemed to be a very appropriate
      species for this investigation, both because of their complex vocal behaviour
      that implies different levels of categorization and their neuronal responses
      towards complex song elements. Multi-unit recordings were performed in wild
      starlings that were awake. The method of backward correlation was used to
      visualize the functional organization and we represented the neuronal responses
      as both activity maps and correlation maps. The use of natural sounds allowed us
      to define several functional sub-areas with different neuronal processing. These
      results show that field L is involved in a more complex task than simple
      frequency processing.

PMID- 15996841
TI  - Biologically active bisbenzylisoquinoline alkaloids from the root bark of
      Epinetrum villosum.
AB  - Methanol and water extracts of the root of Epinetrum villosum (Exell) Troupin
      (Menispermaceae) were found to exhibit antimicrobial and antiplasmodial
      activities. Investigation of the active methanol fraction led to the isolation of
      four bisbenzylisoquinoline alkaloids, i.e., cycleanine, cycleanine N-oxide,
      isochondodendrine and cocsoline. Structures were established by spectroscopic
      methods. Cocsoline displayed antibacterial and antifungal activities (MIC values
      of 1000-15.62 and 31.25 microg/ml, respectively). Isochondodendrine was found to
      have the most potent antiplasmodial activity (IC50 = 0.10 microg/ml), whereas the
      IC50 on HCT-116 human colon carcinoma cells was 17.5 microg/ml (selectivity index
      175). Cycleanine acted against HIV-2 (EC50=1.83 microg/ml) but was at least 10
      fold less active against HIV-1. Cycleanine N-oxide showed no activity towards all
      tested microorganisms.

PMID- 15996842
TI  - Bioguided isolation of pharmacologically active plant components, still a
      valuable strategy for the finding of new lead compounds?
AB  - The position of natural products research in the drug discovery and development
      process nowadays is discussed. A flow chart for the study of plants used in
      traditional medicine, and the composition of a multidisciplinary research team
      for the investigation of medicinal plants are presented, and some recommendations
      are made for the future of bioassay-guided isolations and the use of standardised
      plant extracts in developing countries.

PMID- 15996843
TI  - Is traditional medicine better off 25 years later?

PMID- 15996844
TI  - Bioactive pectic polysaccharides from Glinus oppositifolius (L.) Aug. DC., a
      Malian medicinal plant, isolation and partial characterization.
AB  - Glinus oppositifolius (L.) Aug. DC. (Aizoaceae) is a Malian medicinal plant used
      against various types of illnesses related to the immune response, like joint
      pains, inflammations, fever, malaria and wounds. Two pectin type polysaccharides,
      GOA1 and GOA2, being isolated from a 50 degrees C water extract from the aerial
      parts of Glinus oppositifolius were investigated for their activity towards the
      complement system and different leukocyte subsets because of the assumed effects
      on conditions related to the immune system. The polysaccharide polymer in GOA1
      was shown to contain considerable amounts of the neutral sugars arabinose (26.4
      mol%) and galactose (42.9 mol%), and methylation analysis indicated the presence
      of arabinogalactans type I (AG-I) and type II (AG-II). GOA2 was rich in
      galacturonic acid (68.3 mol%), along with rhamnose, arabinose and galactose.
      Structural studies indicated that rhamnose and galacturonic acid might constitute
      a rhamnogalacturonan backbone, often found in pectic substances, with side chains
      consisting of arabinose and galactose. Both GOA1 and GOA2 were shown to exhibit
      potent dose-dependent complement fixating activities, and induced chemotaxis of
      macrophages, T cells and NK cells.

PMID- 15996845
TI  - Alternative light source (polilight) illumination with digital image analysis
      does not assist in determining the age of bruises.
AB  - The age of a bruise may be of interest to forensic investigators. Previous
      research has demonstrated that an alternative light source may assist in the
      visualisation of faint or non-visible bruises. This project aimed to determine if
      an alternative light source could be utilised to assist investigators estimate
      the age of a bruise. Forty braises, sustained from blunt force trauma, were
      examined from 30 healthy subjects. The age of the bruises ranged from 2 to 231 h
      (mean = 74.6, median = 69.0). Alternative light source (polilight) illumination
      at 415 and 450 nm was used. The black and white photographs obtained were
      assessed using densitometry. A statistical analysis indicated that there was no
      correlation between time and the mean densitometry values. The alternative light
      source used in this study was unable to assist in determining the age of a
      bruise.

PMID- 15996846
TI  - Low radiation dose multislice CT colonography in children: Experience after 100
      studies.
AB  - The purpose of this study was to determine the sensitivity (S) and specificity
      (sp) of virtual colonoscopy in the detection of elevated lesions in children, and
      to compare these results with conventional colonoscopy. Between April 2000 and
      January 2003, 100 patients (mean: 6 years old) were evaluated with virtual
      colonoscopy and conventional colonoscopy. All patients presented rectal bleeding
      and both methods were performed the same day. All patients had received a
      standard bowel cleansing the day before. Virtual colonoscopies were carried out
      with 2.5 mm thick slices, 1.3 mm reconstruction intervals, 15 mAs, and 90 kV. The
      acquisition time ranged from 5-10 s depending on the age of the patient. For each
      method, two scans were performed in both a supine and a prone position. After the
      acquisitions, images were reprocessed using two-dimensional, volume rendering,
      and virtual endoscopy reconstructions. Findings of the two methods were compared
      blinded. They were classified in two groups: (1) normal studies, and (2) elevated
      lesions studies. The second group was subdivided according to the diameter of the
      lesions: (2a) <5 mm, (2b) 5-9 mm, and (2c) >9 mm. All studies were performed
      without complications. Forty-eight patients were normal. In the other 52
      patients, virtual colonoscopy detected 86 lesions, whereas conventional
      colonoscopy depicted only 80 lesions. There were 70 true-positive findings, 48
      true-negative findings, 12 false-positive findings, and 8 false-negative
      findings. The global S was 89%, sp: 80%, positive predictive value: 85%, and
      negative predictive value: 85%. In group (2a), sensitivity, specificity, positive
      predictive value, and negative predictive value were 81, 90, 81, and 90%
      respectively; in group (2b), 90, 90, 85, and 94%, respectively; and in group
      (2c), 100, 96, 90, and 100%, respectively. We concluded that virtual colonoscopy
      is an alternative method for the evaluation of children with elevated lesions. It
      is fast, has no complications, and uses a low radiation dose.

PMID- 15996847
TI  - Analytical methodology for assessment of food allergens: opportunities and
      challenges.
AB  - This review summarizes the available in vitro, in vivo, and informatic methods
      designed to evaluate different aspects of the capacity of proteins to act as true
      food allergens. By now, there is no single method to fully assess the potential
      allergenicity of proteins. The characterization of many food allergens will help
      to uncover the sequential and structural motifs that determine the behaviour of
      proteins as food allergens.

PMID- 15996848
TI  - Phagocytic capacity and apoptosis of peripheral blood cells from patients with
      iron deficiency anemia.
AB  - Following clinical observations that patients with iron deficiency anemia (IDA)
      are more susceptible to infections than non-anemic individuals, the phagocytic
      capacity and number of apoptotic peripheral white blood cells (PWBC) from
      patients with IDA were examined. PWBC from 15 patients with IDA and from 18
      healthy donors were incubated with various doses of iron. Phagocytosis was
      examined using latex particles and apoptosis was evaluated by a flow cytometric
      assay using propidium iodide staining. The percentage of phagocyting
      polymorphonuclear cells was lower in IDA patients compared to that of the
      controls. However, there was no difference in the percentage of phagocyting
      monocytes from individuals of both groups. The number of latex beads engulfed by
      each polymorphonuclear or monocyte was lower in IDA patients. Incubation with 100
      microg% of iron did not affect the phagocytic ability of both cell types in IDA
      patients, but increased that of control cells. Incubation with 300 microg% of
      iron caused an increase in the phagocytic capacity of patients' cells and a
      decrease in that function in cells from controls. Higher dose (500 microg%)
      induced suppression of phagocytosis in cells from both groups. There was no
      difference in the number of apoptotic cells from individuals of both groups.
      Apoptosis of polymorphonuclears, but not mononuclear cells from both controls and
      IDA patients showed a linear dependency on the iron concentration in the medium.
      It is possible that the impaired phagocytic capacity of the PBWC found in
      patients with IDA contribute to the increased susceptibility to infections
      observed in these individuals.

PMID- 15996849
TI  - Regulatory expression of lipoxin A4 receptor in physiologically estrus cycle and
      pathologically endometriosis.
AB  - Expression of receptors for prostaglandin (PG) and leukotriene (LT) has been
      reported to detect in endometrium and smooth muscle of uterus, suggesting
      involvement of these arachidonic metabolites in endometrial pathology and
      reproductive biology. Lipoxin (LX), which is produced by lipoxygenases from
      arachidonic acid, has been characterized as an anti-inflammatory lipid mediator.
      Biological actions of Lipoxin A4 (LXA4) are mediated through the specific
      receptor. In order to know roles of LXA4 in female genitalia, expression of LXA4
      receptor mRNA was quantified by real-time polymerase chain reaction.
      Significantly higher expression of the receptor was detected in endometrium and
      myometrium than ovary in normal rats. Expression of the receptor in endometrium
      was increased at stage of proestrus cycle under physiological condition.
      Exogenous administration of progesterone into female rats significantly reduced
      the expression, while administration of estradiol or pregnant mare serum
      gonadotropin (PMSG) did not. Both, endometrium in experimental endometriosis
      induced in rats and the tissues from patients with ectopic endometriosis showed a
      higher expression of LXA4 receptor compared to the normal tissues. In contrast,
      expressions of BLT1 and BLT2, receptors for leukotriene B4, did not change in the
      endometriosis. These observations suggest a possible role of LXA4 and the
      receptor under physiological estrus cycle and pathological condition as
      endometriosis.

PMID- 15996850
TI  - L-arginine and polyamine administration protect beta-cells against alloxan
      diabetogenic effect in Sprague-Dawley rats.
AB  - In the searching for new substances with the capacity to protect beta-cells from
      the toxic effects of alloxan, we evaluated the effect of L-arginine and the
      polyamines putrescine, spermidine and spermine in a murine experimental model of
      diabetes. Diabetes was induced by the i.p. injection of either 200 mg/kg (24-h
      experiments) or 120 mg/kg (12 days experiments) body weight. L-Arginine and
      polyamines were administered 10 min before or 10 min after alloxan
      administration, once its half-life had elapsed, respectively. In the 24-h study,
      serum glucose (199.8+/-27.6 mg/dl) and triglyceride (54.6+/-4.9 mg/dl)
      concentrations showed a protective effect of spermine, as these parameters were
      not too high (P < or = 0.05), compared to the alloxan-treated group (415.4+/-47.8
      and 90.2+/-11.6 mg/dl, respectively), and were closer to glucose (132.3+/-6.0
      mg/dl) and similar to triglycerides (63.8+/-7.1 mg/dl) of the control group. A
      similar pattern was observed on the parameters measured when L-arginine and
      polyamines were administered daily for 12 days, starting 10 min after a single
      alloxan administration, which provides evidence that L-arginine and polyamines
      are effective in impeding the increase in serum glucose, triglyceride and
      cholesterol concentration showed on day 3 by the alloxan-treated group, as well
      as a higher acinar cell regenerative capacity as determined by
      immunohistochemical techniques. Spermine turning out to be more effective than L
      arginine, putrescine or spermidine in counteracting the marked hyperglycemia and
      triglyceridemia showed by the alloxan-treated group and similar in effect when
      evaluating cholesterolemia. These results show a clear protective role of L
      arginine and polyamines over the pancreatic beta-cell, in addition to the
      induction of neogenesis from both ductal and acinar cells that leads to the
      recovery of endocrine pancreatic function in rats with experimental diabetes.

PMID- 15996851
TI  - An online interactive simulation system for medical imaging education.
AB  - This report presents a recently developed web-based medical imaging simulation
      system for teaching students or other trainees who plan to work in the medical
      imaging field. The increased importance of computer and information technology
      widely applied to different imaging techniques in clinics and medical research
      necessitates a comprehensive medical imaging education program. A complete
      tutorial of simulations introducing popular imaging modalities, such as X-ray,
      MRI, CT, ultrasound and PET, forms an essential component of such an education.
      Internet technologies provide a vehicle to carry medical imaging education
      online. There exist a number of internet-based medical imaging hyper-books or
      online documentations. However, there are few providing interactive computational
      simulations. We focus on delivering knowledge of the physical principles and
      engineering implementation of medical imaging techniques through an interactive
      website environment. The online medical imaging simulation system presented in
      this report outlines basic principles underlying different imaging techniques and
      image processing algorithms and offers trainees an interactive virtual
      laboratory. For education purposes, this system aims to provide general
      understanding of each imaging modality with comprehensive explanations, ample
      illustrations and copious references as its thrust, rather than complex physics
      or detailed math. This report specifically describes the development of the
      tutorial for commonly used medical imaging modalities. An internet-accessible
      interface is used to simulate various imaging algorithms with user-adjustable
      parameters. The tutorial is under the MATLAB Web Server environment. Macromedia
      Director MX is used to develop interactive animations integrating theory with
      graphic-oriented simulations. HTML and JavaScript are used to enable a user to
      explore these modules online in a web browser. Numerous multiple choice
      questions, links and references for advanced study are provided in the tutorial
      for trainees to verify their understanding of each unit. It is expected that this
      tutorial will enhance medical imaging education, help trainees in subsequent
      analysis of image data, and form the basis for the development of more advanced
      technologies in the future.

PMID- 15996852
TI  - 3D localization of clustered microcalcifications using cranio-caudal and medio
      lateral oblique views.
AB  - This paper presents a 3D localization method to register clustered
      microcalcifications on mammograms from cranio-caudal (CC) and medio-lateral
      oblique (MLO) views. The method consists of three major components: registration
      of clustered microcalcifications in CC and MLO views, 3D localization of
      clustered microcalcifications and 3D visualization of clustered
      microcalcifications. The registration is performed based on three features,
      gradient, energy and local entropy codes that are independent of spatial
      locations of microcalcifications in two different views and are prioritized by
      discriminability in a binary decision tree. The 3D localization is determined by
      a sequence of coordinate corrections of calcified pixels using the breast nipple
      as a controlling point. Finally, the 3D visualization implements a virtual
      reality modeling language viewer (VRMLV) to view the exact location of the lesion
      as a guide for needle biopsy. In order to validate our proposed 3D localization
      system, a set of breast lesions, which appear both in mammograms and in MR Images
      is used for experiments where the depth of clustered microcalcifications can be
      verified by the MR images.

PMID- 15996853
TI  - Three-dimensional analysis of complex branching vessels in confocal microscopy
      images.
AB  - The characteristic of confocal microscopy (CM) vascular data is that it contains
      many tiny vessels with branching and complex structure. In this work, an
      automated method for quantitative analysis and reconstruction of cerebral vessels
      from CM images is presented in which the extracted centerline of the vessels
      plays the key role. To assess the efficiency and accuracy of different centerline
      extraction methods, a comparison among three fully automated approaches is given.
      The centerline extraction methods studied in this work are a snake model, a path
      planning approach, and a distance transform-based method. To evaluate the
      accuracy of the quantitative parameters of vessels such as length and diameter,
      we apply the method to synthetic data. These results indicate that the snake
      model and the path planning method are more accurate in extracting the
      quantitative parameters. The efficiency of the approach in clinical applications
      is then confirmed by applying the method to real CM images. All three methods
      investigated in this work are accurate enough to correctly distinguish between
      normal and stroke brain data, while the snake model is the fastest for clinical
      applications. In addition, three-dimensional visualization, reconstruction, and
      characterization of CM vascular images of rat brains are presented.

PMID- 15996854
TI  - Intra-operative visualisation of 3D temperature maps and 3D navigation during
      tissue cryoablation.
AB  - Thermotherapeutic tools are increasingly used for tissue ablation, although the
      intra-operative monitoring is not adequate for such procedures. This is a main
      challenge for more extensive use of any ablative technique. The present work
      focuses on treatment of hepatic tumours by cryo therapy. For any
      thermotherapeutic tool there are specific thermal conditions that have to be met
      to ensure treatment adequacy. A software tool was made to calculate and visualise
      3D temperature distributions during hepatic cryoablation combined with a 3D intra
      operative navigation system. This system aids the user in placing the cryoprobe
      using an optical tracking system and 3D visualisation of the probe placement in
      relation to the target anatomy and the planned trajectory. 3D temperature
      distributions are calculated and visualized intra-operatively. The system is
      integrated with an interventional Magnetic Resonance 0.5T scanner. The system was
      tested in an animal experiment, exemplifying the usefulness of the navigation
      system and its ability to give intuitive feedback to the user on thermodynamic
      conditions induced in the target region. The system constitutes a novel tool for
      enhanced intra-operative control during cryoablative procedures, and motivates
      for studies using this tool to investigate predictors applied as indicators of
      treatment adequacy and patient outcome.

PMID- 15996855
TI  - The consequences of Conduct Disorder for males who develop schizophrenia:
      associations with criminality, aggressive behavior, substance use, and
      psychiatric services.
AB  - Men with schizophrenia are at increased risk, as compared to the general
      population, for criminal offending and to have displayed Conduct Disorder (CD)
      before age 15. The present study examined the consequences of CD among a sample
      of 248 men with schizophrenia or schizo-affective disorder, aged, on average, 39
      years old. Participants were intensively assessed at discharge from the hospital
      and four times during the subsequent two-year period. CD was associated with
      criminality and substance misuse among first-degree male relatives and substance
      misuse among female relatives. In childhood and adolescence, CD was associated
      with poor academic performance, substance abuse, and physical abuse. In
      adulthood, the diagnosis of CD and each CD symptom were associated with increased
      non-violent and violent criminal offending, after adjusting for life-time
      diagnoses of substance misuse disorders. CD was not associated with homicide. CD
      was associated with life-time diagnoses of alcohol and drug abuse and/or
      dependence. During the 24 month follow-up period, CD and the number of CD
      symptoms were associated with aggressive behavior, controlling for life-time
      diagnoses of substance use disorders, substance misuse measured objectively and
      subjectively, medication compliance, and obligatory care. CD was associated with
      an earlier age at onset of schizophrenia and at first admission to hospital, and
      with length of time spent in hospital. During the two-year follow-up period,
      neither the diagnosis of CD nor the number of CD symptoms was associated with
      levels of positive and negative symptoms assessed five times, compliance with
      medication, substance use, or readmission. The results are interpreted to suggest
      that CD is a distinct co-morbid disorder that runs parallel to the course of
      schizophrenia.

PMID- 15996856
TI  - No sequence dependent modulation of the Simon effect in Parkinson's disease.
AB  - This study sought to evaluate impaired response tendencies and modulation of
      automatic processes in Parkinson's disease (PD), utilising a saccadic Simon task
      with stimulus-response (S-R) compatibility determined on the basis of cue shape.
      The appearance of either a circle or a square in one of two boxes presented
      peripherally required the generation of a leftward or rightward horizontal
      saccade, respectively. These goal-directed responses were considered
      behaviourally relevant to an examination of visuospatial performance. Although
      response times are typically faster when stimulus and response are spatially
      compatible than when they are not, sequence-dependent modulation of this effect
      results in large differences between S-R compatible and S-R incompatible trials
      when stimulus and response are spatially compatible in the preceding trial, and
      reduced or absent differences when stimulus and response are spatially
      incompatible in the preceding trial. Unlike control subjects, PD patients
      demonstrated significantly shorter saccadic latencies overall, compared to a
      baseline condition involving endogenously-driven saccades. Patients also
      responded erroneously to cue stimuli with greater frequency. Analyses of both
      saccadic latency and errors to cue demonstrated a Simon effect (relatively faster
      response for S-R compatible trials), irrespective of the preceding trial. This
      suggests impaired modulation of the Simon effect in PD, consistent with
      predictions of inhibitory dysfunction, or impaired episodic memory. These results
      demonstrate the pivotal role of the basal ganglia in the regulation of context
      dependent neural activity.

PMID- 15996857
TI  - On beyond mirror neurons: internal representations subserving imitation and
      recognition of skilled object-related actions in humans.
AB  - A considerable recent literature argues that the same representations, encoded by
      inferior prefrontal and parietal cells known as "mirror neurons", may be
      activated in both production and recognition of object-related actions. Here, we
      test several predictions derived from the contemporary literature on the parity
      between production and recognition and the putative emergence of the mirror
      neuron system from a system coding hand-object interactions. Forty-four patients
      with left-hemisphere stroke, 21 of whom exhibited ideomotor apraxia, performed a
      number of pantomime imitation and recognition tasks, and performance was scored
      with respect to hand posture, arm posture, amplitude, and timing. Consistent with
      predictions, there were strong relationships between object-related pantomime
      imitation and object-related pantomime recognition, and between imitation and
      recognition of the hand posture component of object-related actions. Skilled
      object-related gesture representations are likely to be closely tied to
      evolutionarily more primitive systems controlling object grasping, to emerge from
      a mapping between object and action information coded by ventral and dorsal
      streams, and to be lateralized to the left hemisphere in humans.

PMID- 15996859
TI  - Hearing problems and acoustic neuroma cancer in Sweden.

PMID- 15996858
TI  - Activation of mitogen activated protein kinase pathways and melanogenesis by
      novel nitro-derivatives of 7-hydroxycomarin in human malignant melanoma cells.
AB  - 6-Nitro-7-hydroxycoumarin (6-NO2-7-OHC) and 3,6,8-trinitro-7-hydroxycoumarin
      (3,6,8-NO2-7-OHC) have previously been shown to be potent and selective anti
      proliferative agents in a human melanoma cell line. These agents functioned by
      decreasing DNA synthesis, through an inhibition of the S phase regulatory
      protein, cyclin A. However, the key molecular target(s) for these drugs remained
      undefined. Here, we attempted to elucidate the exact nature of the relationship
      between drug exposure and signal transduction, particularly their effects on the
      mitogen activated protein kinase (MAPK) cascades, and the consequent effect on
      cell growth, death and differentiation. Comparative studies were carried out
      using 7-hydroxycoumarin (7-OHC). Both nitro-derivatives were found to alter the
      phosphorylation status of ERK1/ERK2 and p38. However, 7-OHC exerted this effect
      only at higher concentrations and longer incubation times. Also, none of the
      three drugs had any effect on SAPK phosphorylation. Tyrosinase activity assays
      and morphological studies were used to show drug-induced effects on cellular
      differentiation. Unlike 7-OHC, both 6-NO2-7-OHC and 3,6,8-NO2-7-OHC caused a
      dramatic increase in tyrosinase activity in a manner similar to the cAMP
      elevating agent, forskolin. Also, the MEK inhibitor (PD98059) in combination with
      nitro-derivatives stimulated an even greater increase in tyrosinase activity when
      compared to either drug. In addition, the p38 inhibitor (SB203580) reduced the
      activity of both drugs. Morphological examination of treated cells showed nitro
      derivatives caused changes consistent with altered cellular differentiation.
      Taken together, we have established that exposure of human malignant melanoma
      cells to these drugs leads to a modulation of p38 MAP kinase phosphorylation.
      This implies that these drugs may function by altering both melanogenesis and
      cellular differentiation. However, their effect on the levels of these proteins
      rather than their phosphorylation status remains to be determined. Therefore,
      additional studies are underway in order to identify the exact binding partners
      for these drugs.

PMID- 15996860
TI  - An expert study evaluating the UMLS lexical metaschema.
AB  - OBJECTIVE: A metaschema is an abstraction network of the UMLS's semantic network
      (SN) obtained from a connected partition of its collection of semantic types. A
      lexical metaschema was previously derived based on a lexical partition which
      partitioned the SN into semantic-type groups using identical word-usage among the
      names of semantic types and the definitions of their respective children. In this
      paper, a statistical analysis methodology is presented to evaluate the lexical
      metaschema based on a study involving a group of established UMLS experts.
      METHODS: In the study, each expert was asked to identify subject areas of the SN
      based on his or her understanding of the various semantic types. For this
      purpose, the expert scans the SN hierarchy top-down, identifying semantic types,
      which are important and different enough from their parent semantic types, as
      roots of their groups. From the response of each expert, an "expert metaschema"
      is constructed. The different experts' metaschemas can vary widely. So,
      additional metaschemas are obtained from aggregations of the experts' responses.
      Of special interest is the consensus metaschema which represents an aggregation
      of a simple majority of the experts' responses. Statistical analysis comparing
      the lexical metaschema with the experts' metaschemas and the consensus metaschema
      is presented. RESULTS: The analysis results shows that 17 out of the 21 meta
      semantic types in the lexical metaschema also appear in the consensus metaschema
      (about 81%). There are 107 semantic types (about 79%) covered by identical meta
      semantic types and refinements. The results show the high similarity between the
      two metaschemas. Furthermore, the statistical analysis shows that the lexical
      metaschema did not grossly underperform compared to the experts. CONCLUSION: Our
      study shows that the lexical metaschema provides a good approximation for a
      partition of meaningful subject areas in the SN, when compared to the consensus
      metaschema capturing the aggregation of a simple majority of the human experts'
      opinions.

PMID- 15996861
TI  - Expression of 15-lipoxygenase-1 in human nasal epithelium: its implication in
      mucociliary differentiation.
AB  - 15-lipoxygenase-1 (15-LO-1) is involved in the differentiation of human
      tracheobronchial epithelial cells. Here, we investigated the relation between 15
      LO-1 expression and the differentiation of human nasal epithelium. In retinoic
      acid (RA)-sufficient culture media, 15-LO-1 expression in normal human nasal
      epithelial cell time-dependently increased, but its expression was undetectable
      in RA-deficient culture media. Moreover, in RA-deficient culture media, IL-4 at 1
      ng/ml concentration time-dependently induced 15-LO-1 expression. In addition,
      MUC8 gene expression, a marker of mucociliary differentiation, was up-regulated
      by 15-LO-1, which was itself induced by IL-4. In murine nasal mucosa, the
      expression of leukocyte type-12-LO, a functional equivalent of 15-LO-1, reduced
      after postnatal day 7. Our findings suggest that 15-LO-1 is related to the
      differentiation of human nasal epithelium, and that it may mediate the
      mucociliary differentiation of human nasal epithelium.

PMID- 15996862
TI  - Predicting the compressibility behaviour of tire shred samples for landfill
      applications.
AB  - Tire shreds have been used as an alternative to crushed stones (gravel) as
      drainage media in landfill leachate collection systems. The highly compressible
      nature of tire shreds (25-47% axial strain on vertical stress applications of 20
      700 kPa) may reduce the thickness of the tire shred drainage layer to less than
      300 mm (minimum design requirement) during the life of the municipal solid waste
      landfill. There hence exists a need to predict axial strains of tire shred
      samples in response to vertical stress applications so that the initial thickness
      of the tire shred drainage layer can be corrected for compression. The present
      study performs one-dimensional compressibility tests on four tire shred samples
      and compares the results with stress/strain curves from other studies. The
      stress/strain curves are developed into charts for choosing the correct initial
      thickness of tire shred layers that maintain the minimum thickness of 300 mm
      throughout the life of the landfill. The charts are developed for a range of
      vertical stresses based on the design height of municipal waste cell and bulk
      unit weight of municipal waste. Experimental results also showed that despite
      experiencing large axial strains, the average permeability of the tire shred
      sample consistently remained two to three orders of magnitude higher than the
      design performance criterion of 0.01cm/s for landfill drainage layers. Laboratory
      experiments, however, need to verify whether long-term chemical and bio-chemical
      reactions between landfill leachate and the tire shred layer will deteriorate
      their mechanical functions (hydraulic conductivity, compressibility, strength)
      beyond permissible limits for geotechnical applications.

PMID- 15996863
TI  - Aromatase inhibitors: combinations with fulvestrant or signal transduction
      inhibitors as a strategy to overcome endocrine resistance.
AB  - There is an increasing rationale for effective combinations of endocrine therapy
      with novel drugs that target aberrant signal transduction pathways in estrogen
      receptor (ER) positive breast cancer. Prolonged endocrine therapy can be
      associated with an acquired increase in peptide growth factor signaling (EGFR,
      HER2), together with cross-talk activation of ER-dependent gene transcription and
      cell growth that leads to endocrine resistance. Current approaches to target
      these pathways include both the selective ER downregulator fulvestrant, and
      various signal transduction inhibitors (STIs). Fulvestrant can overcome
      resistance to tamoxifen (TAM-R) and long-term estrogen deprivation (LTED-R) in
      experimental models by reducing ER expression, and represents a current option
      for post-menopausal women with endocrine resistant ER+ve breast cancer. Emerging
      data suggest that fulvestrant's effect may be greater when combined with estrogen
      deprivation, and several phase III trials are assessing fulvestrant combined with
      aromatase inhibitors (AIs). Small molecule STIs such as tyrosine kinase
      inhibitors (TKIs), farnesyltransferase inhibitors (FTIs) and mTOR antagonists are
      also active in breast cancer. Pre-clinical data suggest that combined
      endocrine/STI therapy may result in greater growth inhibition than either therapy
      alone, and thus delay emergence of resistance. Several clinical trials are now
      examining STIs combined with AIs both in the tamoxifen-resistant and first-line
      advanced breast cancer setting, while pre-surgical studies are investigating the
      efficacy of combined endocrine/STI therapy utilising biological primary
      endpoints. This article reviews the pre-clinical rationale for this strategy and
      the clinical trials in this area.

PMID- 15996864
TI  - Interobserver agreement and consensus over the esthetic evaluation of
      conservative treatment for breast cancer.
AB  - Twenty-four experts from 13 different countries were asked to evaluate
      photographs taken of 60 women following conservative breast cancer treatment. The
      esthetic result of each case was classified as poor, fair, good or excellent.
      Agreement was evaluated using the kappa (k) and weighted kappa (wk) statistics,
      for all observers, male and female participants, those younger and older than 50
      years, those seeing more than 250 cases a year, and those with previous
      publications in this area. Consensus was obtained by way of a modified Delphi
      approach, when more than 50% of participants provided the same classification. In
      a second round, consensual cases were disclosed and a revised opinion was asked
      in non-consensual ones. Agreement between all participants was fair (k=0.24,
      wk=0.37) and remained within the same range (k=0.20-0.31, wk=0.31-0.45) in the
      subgroups analyzed. First round consensus was obtained in 46 out of 60 cases
      (77%) and in the second round in 59 out of 60 cases (98%). Evaluation of the
      esthetic results of conservative treatment for breast cancer is only fairly
      reproducible when performed by experts working in different geographical areas.
      Consensus is obtainable if a relatively low threshold of agreement is considered
      acceptable.

PMID- 15996865
TI  - Occult breast cancer presenting as axillary metastases.
AB  - We report the case of a 52-year-old woman with occult breast cancer who presented
      with a hard metastatic nodule in the left axilla. Although histology identified a
      metastatic adenocarcinoma in the lymph nodes, numerous tests failed to detect the
      primary tumor. Immunohistochemistry showed that the resected lymph node was
      positive for both estrogen and progesterone receptors, suggesting the breast as
      the site of the primary tumor. Left modified radical mastectomy was performed.
      Pathology revealed an invasive ductal carcinoma (1.5x1 mm in size) with extensive
      lymphatic involvement, which strongly expressed both vascular endothelial growth
      factor-C (VEGF-C) and VEGF-D.

PMID- 15996866
TI  - HIF-1alpha and p53: the ODD couple?
AB  - Tumor hypoxia activates hypoxia-inducible factor-1 (HIF-1) and induces the
      accumulation of the tumor suppressor p53. HIF-1 signaling stimulates angiogenesis
      and mediates cellular adaptation to hypoxia, whereas p53 promotes hypoxia-induced
      apoptosis. A recent article provides in vitro biophysical evidence supporting a
      direct interaction between p53 and the oxygen-dependent degradation domain of the
      HIF-1alpha subunit. The article identifies potential structural parameters
      required for this interaction and suggests an alternative mechanism by which p53
      might impact tumor response to therapy.

PMID- 15996867
TI  - Small non-coding RNAs as magic bullets.
AB  - RNA interference (RNAi) - inhibition of gene expression by small, non-coding RNAs
      [small interfering RNAs (siRNAs) or microRNAs (miRNAs)] - has changed our view of
      regulation of expression dramatically. The application of siRNAs for both
      functional analysis of genes and medication raises several questions. These
      include the design of the double-stranded oligonucleotides, their preparation and
      introduction into cells or animals either as chemically synthesized entities or
      as transcripts from a suitable vector. Delivery of the oligonucleotides, choice
      of vector, chemical modification to stabilize against nucleases and avoidance of
      side effects (e.g. stimulation of interferons) are major challenges. Work to
      identify the multiple targets of miRNAs is still in its infancy, and a clear
      distinction between siRNAs and miRNAs is difficult in some instances. Moreover,
      transcriptional silencing by RNAi is poorly understood; it is evident that the
      siRNA machinery is involved but the details await clarification. Given the
      multitude of interactions of the small non-coding RNAs revealed so far, we should
      be prepared to encounter, as yet, undiscovered interactions and mechanisms.

PMID- 15996868
TI  - Ironing out the problem: new mechanisms of iron homeostasis.
AB  - For most organisms, iron is an essential nutrient that is both difficult to
      acquire from the environment and toxic at high concentration. Therefore, to avoid
      deprivation or over-abundance of iron, bacteria and eukaryotes have developed a
      tight regulatory system to keep the metal within a narrow concentration range.
      Recent work in the bacteria Escherichia coli and in Pseudomonas aeruginosa has
      demonstrated that small regulatory RNAs function post-transcriptionally to
      repress iron-using proteins, thereby ensuring that limited iron resources are
      allocated to crucial cellular functions during iron starvation. Following this
      discovery, a parallel mechanism that uses a protein and not a small RNA was
      described in the budding yeast Saccharomyces cerevisiae under iron restriction.
      The common characteristics of these three different organisms suggest a novel
      mechanism of iron homeostasis.

PMID- 15996869
TI  - Detergent-resistant membranes should not be identified with membrane rafts.
AB  - Three originally distinct concepts - lipid rafts, detergent-resistant membranes
      (DRMs) and liquid-ordered (lo) lipid phases - are often confused in current
      literature; many researchers have assumed that all three names refer to the same
      chemico-biological entity. In fact, theoretical and experimental findings provide
      strong evidence against identifying DRMs with rafts and lo domains. Because much
      of what we think we know about lipid rafts is based on their unjustified
      identification as DRMs, functional domains in biological membranes might differ
      markedly from the generally accepted picture.

PMID- 15996870
TI  - Scaffold proteins dictate Rho GTPase-signaling specificity.
AB  - Given the numerous mechanisms that regulate the activity of Rho GTPases and the
      multiple effectors for Rho proteins, how is specificity achieved when transducing
      signals via Rho GTPase-regulated molecular networks? The finding that the
      scaffold protein hCNK1 links Rho guanine-nucleotide-exchange factors and Rho to
      JNK (c-Jun N-terminal kinase), while limiting stress-fiber formation and serum
      response-factor activation, suggests that scaffold proteins govern the selection
      of signal outputs, thus helping to solve the Rho GTPase-signaling puzzle.

PMID- 15996871
TI  - Oxidative activation of antioxidant defence.
AB  - Living cells maintain a delicate balance between oxidizing and reducing species,
      and many disorders such as rheumatoid arthritis and Alzheimer's disease have been
      associated with a disturbed intracellular 'redox equilibrium'. The past few years
      have witnessed accelerated research into how natural redox responses and
      antioxidant defence systems are activated and how they restore a healthy redox
      balance. To function properly, many of these processes rely on a powerful sulfur
      redox chemistry, which is best exemplified by the complex, newly emerging
      cysteine-based redox regulation of the glutathione and thioredoxin pathways.
      Other redox systems based on oxidatively activated amino acid side chains in
      proteins are also becoming increasingly important, but are still barely
      understood or explored.

PMID- 15996872
TI  - Novel synthesis and anti-inflammatory activities of 2,5-disubstituted
      dioxacycloalkanes.
AB  - A novel stereospecific synthetic route to obtain a series of 2,5-disubstituted
      dioxacycloalkanes is reported. Using an in vivo inhibition assay by monitoring
      xylene-induced ear edema in mice, the structure-activity relationship of the
      dioxacycloalkane compounds was studied, and compounds possessing high anti
      inflammatory activity were identified.

PMID- 15996873
TI  - Calculation of fluence to dose conversion coefficients in partial exposure.
AB  - Organ doses and effective doses of electrons and photons for the partial exposure
      using the MIRD-5 phantom and EGS-4 Code have been calculated. Irradiation
      geometries are AP and PA exposure. Calculations are carried out using 5
      isocentered beams with different sizes to investigate the beam sizes effect on
      the effective dose. The results show that the effective doses depend not only on
      the energy of incident particle but also on the exposure position and the beam
      size on the body.

PMID- 15996874
TI  - Application of neutron generators for high explosives, toxic agents and fissile
      material detection.
AB  - The portable pulsed neutron generators developed and designed by VNIIA are
      presented. The neutron methods are good tools for non-destructive assay of
      dangerous materials. The samples of various systems for the detection of high
      explosives in luggage, identification of toxic agents in chemical munitions, and
      also for the prevention of illicit trafficking of fissile elements in passengers'
      luggage are discussed.

PMID- 15996875
TI  - Radiation oncology practice accreditation: the American College of Radiation
      Oncology, Practice Accreditation Program, guidelines and standards.
AB  - The American College of Radiation Oncology Practice Accreditation Program (ACRO
      PAP) is a process by which a medical practice is evaluated through an in depth
      external review to ascertain whether or not key components of the practice comply
      with existing regulations, rules, laws, practice guidelines and professional
      practice standards. In radiation oncology, like other fields, it is driven by the
      need or desire to demonstrate an identified level of patient care. The
      accreditation process adopted by the American College of Radiation Oncology
      (ACRO) is based on the parameters of quality care assessment outlined by the
      National Academy of Science's Institute of Medicine. Those practices that meet
      these criteria are eligible for recognition and accreditation by ACRO.

PMID- 15996876
TI  - Vitamin D and type 1 diabetes mellitus: state of the art.
AB  - Recent evidence suggests a role for vitamin D in pathogenesis and prevention of
      diabetes mellitus. Active vitamin D, 1alpha,25(OH)(2)D(3), prevents type 1
      diabetes in animal models, modifies T-cell differentiation, modulates dendritic
      cell action and induces cytokine secretion, shifting the balance to regulatory T
      cells. High-dose vitamin D supplementation early in life protects against type 1
      diabetes. 1alpha,25(OH)(2)D(3) activity is mediated through its receptor, and
      targets include transcriptional regulators; therefore, 1alpha,25(OH)(2)D(3)
      influences gene transcription. 1alpha,25(OH)(2)D(3) also affects pancreatic beta
      cell function. Genomic variations of vitamin D metabolism and target cell action
      predispose to type 1 diabetes. Vitamin D deficiency in pregnancy probably
      increases the incidence of autoimmune diseases, such as type 1 diabetes, in
      genetically predisposed individuals. Pharmacotherapy with 1alpha,25(OH)(2)D(3)
      analogues might help prevent and treat diabetes.

PMID- 15996878
TI  - Anterior cingulate activity during error and autonomic response.
AB  - The contribution of anterior cingulate cortex (ACC) to human cognition remains
      unclear. The rostral (rACC) and dorsal (dACC) ACC cortex are implicated in tasks
      that require increased response control due to emotional and cognitive
      interference, respectively. However, both rACC and dACC are activated by
      conditions that induce changes in visceral arousal, suggesting that ACC supports
      a generation of integrated bodily responses. To clarify the relationship between
      purely cognitive and psychophysiological accounts of ACC function, we scanned 15
      subjects using functional magnetic resonance imaging while they performed
      numerical versions of the Stroop task. To index autonomic arousal, we
      simultaneously measured pupil diameter. Performance errors accounted for most of
      the variance in a pupil-derived measure of evoked autonomic arousal. In analysis
      of the functional imaging data, activity within a region spanning rACC and dACC
      predicted trial-by-trial variation in autonomic response magnitude and was
      enhanced during error trials, shown using conjunction analyses. Activity within
      other loci within rACC predicted evoked autonomic arousal and showed sensitivity
      to errors but did not meet criteria for both. These data highlight the role of
      ACC in psychophysiological aspects of error processing and suggest that an
      interface exists within ACC between cognitive and biobehavioral systems in the
      service of response adaptation.

PMID- 15996880
TI  - Investigation of a putative role for FLVCR, a cytoplasmic heme exporter, in
      Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia.
      Previous studies indicate that mutations of a gene on chromosome 19q13.2, which
      encodes a ribosomal protein, are responsible for 25% of cases. Recent
      investigations suggest both the presence of a second candidate region on
      chromosome 8p and non-19q, non-8p disease. In linkage analysis studies of 28
      multiplex DBA families, we identified 8 families with disease linkage to
      chromosome 1q31. In 4 families, the disease linked exclusively to 1q31. Here, we
      report that the FLVCR gene on 1q31, which encodes a cytoplasmic heme exporter
      associated with red cell aplasia in cats, is not involved in DBA in these
      families.

PMID- 15996879
TI  - Method for improved accuracy in endogenous urea recovery marker calibrations for
      microdialysis in tumors.
AB  - INTRODUCTION: Urea has been proposed as an endogenous recovery marker for
      microdialysis for absolute concentration calculations of analytes in
      microdialysis samples. Previously we demonstrated a linear relationship between
      urea concentrations in a rat mammary carcinoma and that in plasma, validating its
      use as a recovery marker for that particular tumor. In this paper, we have
      extended the validation to two other tumor lines, thereby providing confidence
      that the calibration is constant across tumor types. To improve the accuracy in
      the determination of the plasma/tumor urea relationship from no net flux
      calibrations, we extended the range of the calibration by adding exogenous urea
      to tumor bearing animals. This method enabled more accurate calculations of
      absolute recovery from plasma and dialysate urea concentrations. We confirm that
      by using this method the calibration is valid across three different tumor lines.
      The existence of a common calibration between tumors provides rationale for using
      plasma urea as a recovery marker for clinical trials. The existence of a common
      calibration between tumor types bypasses the need to perform time consuming
      calibrations for each patient. This makes the procedure much more practical for
      clinical studies. METHODS: The no net flux technique was used to determine the
      plasma vs. tumor urea relationship for the R3230Ac mammary carcinoma, 9 L glioma,
      and a fibrosarcoma (FSa), grown in Fischer 344 rats. Plasma urea was stably
      increased beyond the normally occurring concentration for some of the data points
      by subcutaneous bolus administration to extend the range of data for the no net
      flux calibration. RESULTS: Urea recovery was unaffected by plasma urea
      concentration and was consistent with other reported values. The relationship
      between plasma and tumor urea was fit by a line, and linear regressions of the
      data with the extended plasma urea range had better R2 values than we reported
      previously. Statistical comparison of the regressions suggests that within
      reasonable uncertainty limits, they are the same for the different tumor types.
      DISCUSSION: Increasing the plasma urea concentration range for no net flux
      calibrations of urea as an endogenous recovery marker in tumors resulted in more
      accurate determination of the plasma/tumor urea relationship. A single linear
      regression may describe the relationship between plasma and tumor urea
      concentration across tumor lines for a given set of microdialysis parameters.

PMID- 15996881
TI  - Two distinct Indian G6PD variants G6PD Jamnagar and G6PD Rohini caused by the
      same 949 G-->A mutation.
AB  - Earlier we have reported two G6PD variants viz.; G6PD Jamnagar and G6PD Rohini.
      The enzymes from both the variants showed altered biochemical properties with
      mild enzyme deficiency and were classified as unique Class III variants. G6PD
      Jamnagar was found to be associated with drug-induced hemolytic anemia whereas
      G6PD Rohini was picked up during a population survey. Subsequent molecular
      studies on the DNA from both the cases showed the presence of the Kerala-Kalyan
      (949 G-->A) mutation. Hence, this study besides supporting the fact that
      biochemically distinct variants could have the same mutation at the molecular
      level also highlights the importance of molecular characterization of G6PD
      variants.

PMID- 15996882
TI  - Evaluation of respiratory function by barometric whole-body plethysmography in
      healthy dogs.
AB  - The objective of the present study was to assess the validity of barometric whole
      body plethysmography (BWBP), to establish reference values, and to standardise a
      bronchoprovocative test to investigate airway responsiveness using BWBP in
      healthy dogs. BWBP measurements were obtained from six healthy beagle dogs using
      different protocols: (1) during three consecutive periods (3.5min each) in two
      morning and two evening sessions; (2) before and after administration of two
      protocols of sedation; (3) before and after nebulisation of saline and increasing
      concentrations of carbachol and histamine both in conscious dogs and in dogs
      under both protocols of sedation. Enhanced pause (PENH) was used as index of
      bronchoconstriction. Basal BWBP measurements were also obtained in 22 healthy
      dogs of different breeds, age and weight. No significant influence of either time
      spent in the chamber or daytime was found for most respiratory variables but a
      significant dog effect was detected for most variables. A significant body weight
      effect was found on tidal volume and peak flow values (P<0.05). Response to
      carbachol was not reproducible and always associated with side effects.
      Nebulisation of histamine induced a significant increase in respiratory rate,
      peak expiratory flow, peak expiratory flow/peak inspiratory flow ratio and PENH
      (P<0.05). The response was reproduced in each dog at different concentrations of
      histamine. Sedation with acepromazine+buprenorphine had little influence on basal
      measurements and did not change the results of histamine challenge. It was
      concluded that BWBP is a safe, non invasive and reliable technique of
      investigation of lung function in dogs which provides new opportunities to
      characterise respiratory status, to evaluate airway hyperresponsiveness and to
      assess therapeutic interventions.

PMID- 15996883
TI  - Proliferation zones in the salmon telencephalon and evidence for environmental
      influence on proliferation rate.
AB  - Cell proliferation occurs in the brain of fish throughout life. This mitotic
      activity contributes new neurons to some brain subdivisions, suggesting potential
      for plasticity in neural development. Recently we found that the telencephalon in
      salmonids (salmon, trout) is significantly reduced in fish reared in hatcheries
      compared to wild fish, and that these differences resulted in part from rearing
      conditions. Here, we describe localized areas of cell proliferation in the
      telencephalon of juvenile coho salmon (Oncorhynchus kisutch) and begin to explore
      whether mitotic activity in these areas is sensitive to environmental conditions.
      Using the 5-bromo-2'-deoxyuridine (BrdU) cell birth-dating technique, we
      localized proliferating cells in the telencephalon to three distinct zones
      (proliferation zones 1a, 1b, and 2). We measured the volumes of these zones and
      showed that they grew at different rates relative to body size. We also found
      that variation in environmental rearing conditions altered the density of BrdU
      labeled cells in proliferation zone 2, but not in zones 1a or 1b. However, this
      change in mitotic activity did not generate a difference in telencephalon size.
      These results suggest that environmental conditions, and associated changes in
      swimming activity or social structure, may influence rates of cell proliferation
      in the fish forebrain.

PMID- 15996884
TI  - IMP-GMP 5'-nucleotidase in reptiles: occurrence and tissue distribution in a
      crocodile and three species of lizards.
AB  - IMP-hydrolyzing activity (which is reactive with goose anti-pig lung IMP-GMP 5'
      nucleotidase (c-N-II: EC.3.1.3.5) serum) was detected in extracts from several
      tissues (liver, heart, kidney, spleen, stomach, lung and skeletal muscle) from
      constitutively uricotelic reptiles: a crocodile (Crocodylus siamensis), and three
      species of lizard (Furcifer oustaleti, Tupinambis rufescens and Varanus gouldi).
      The activities were markedly high in the livers: 3.0 units/g in the crocodile and
      1.4-2.9 units/g in the lizards. These were similar to those previously reported
      for the livers from chicken and snakes (also constitutively uricotelic), and 4-
      to 10-fold higher than those in ammoniotelic or ureotelic vertebrates. These
      findings suggest that the high activity of IMP-GMP 5'-nucleotidase in the liver
      is a feature of constitutive uricotelism, and that the enzyme may participate in
      the production of uric acid as an end product of amino acid catabolism.

PMID- 15996885
TI  - [Building Clinical Target Volume in laryngeal cancers using knowledge about modes
      of invasion of each location].
AB  - The purpose of this article is to propose a building model to delineate Clinical
      Target Volume in laryngeal cancers (squamous cell carcinoma). This model uses
      histological knowledge about the spread of laryngeal cancers. Firstly is
      described the spread, depending on primary location and anatomic structures. Then
      illustrated examples on Computed Tomography are provided. This delineation
      approach appears to be useful with 3D-CRT and IMRT for adapting dose delivery to
      the complex spread of laryngeal cancer.

PMID- 15996886
TI  - [Multislice CT: technical principles and new trends in medical imaging and
      radiotherapy].
AB  - Development and availability of multislice CT modifies quickly procedures for
      diagnostic and pretherapeutic explorations. This new technology provides many
      advantages such as: to reduce time of examination and to facilitate exploration
      of larger anatomical volumes, to reduce partial volume effects, to enhance the
      ratio signal/noise, to improve intravascular concentration of contrast product
      and then to better identify arterial or venous phases. Use of multislice CT for
      exploration with respiratory gating is also discussed. On the other hand,
      multislice CT requires new requirements as medical time occupation and handling
      of important number of images. Active collaboration between radiologists and
      radiation oncologists is needed to define new acquisition modalities and
      practical ways of co-interpretation.

PMID- 15996887
TI  - The role of urokinase in innate immunity against Staphylococcus aureus.
AB  - Urokinase (uPA) is a serine protease that not only displays fibrinolytic function
      but also promotes host leukocytes to home to inflammatory sites. We have recently
      demonstrated that staphylokinase (SAK), which is a fibrinolytic protein secreted
      by Staphylococcus aureus, forms complexes with human neutrophil peptides (HNPs),
      which are members of the defensin family and have anti-microbial properties,
      thereby inhibiting the bactericidal effects of the HNPs. The aim of this study
      was to assess whether endogenous uPA, which has fibrinolytic properties similar
      to those of SAK, binds to HNPs and interferes with SAK/HNPs interaction. To this
      end, an ELISA was used to analyze the interactions between uPA and HNPs. HMW uPA
      had the ability to bind to both HNP types. The biological consequences of the
      formation of this complex were analyzed with respect to its bactericidal
      properties. HMW uPA killed S. aureus, albeit at relatively high doses (50-100
      mug/ml). In contrast, the binding of HMW uPA to HNPs had no impact on the
      bactericidal functions of the HNPs. Importantly, the addition of HMW uPA to SAK
      eliminated the ability of SAK to neutralize HNPs. Our results demonstrate that
      endogenous HMW uPA inhibits S. aureus growth both directly, by cytolysis, and
      indirectly, by abrogation of the neutralizing effect of SAK on the bactericidal
      activities of HNPs. These findings indicate novel functions of HMW uPA in the
      host defense against staphylococcal infections.

PMID- 15996888
TI  - Hydatid disease in acute leukemia: effect of anticancer treatment on
      echinococcosis.
AB  - Echinococcosis, also known as hydatid disease or hydatidosis, is a zoonotic
      illness caused by the larval form of Echinococcus spp. It is highly prevalent in
      areas where the parasite is endemic such as the Mediterranean region. However,
      occurrence of echinococcosis and cancer together is rare. We treated and followed
      approximately 1200 patients with different hematologic neoplastic diseases
      between 1985 and 2003, and only one of these individuals had concomitant acute
      leukemia and liver hydatidosis. This report describes the case of a 19-year-old
      man who had both primary refractoriness of acute leukemia (AML-M4) and liver
      hydatidosis. Management is discussed. The patient had cystic echinococcosis (CE)
      of the liver that was classified as CE1 according to the system established by
      the World Health Organization's Informal Working Group on Echinococcosis. The
      patient underwent 3 months of treatment with agents that targeted the leukemia
      (daunorubicin, idarubicin, cytarabine, fludarabine) and its complications
      (amphotericin B, amphotericin B lipid complex, liposomal amphotericin B).
      Throughout this period, the size and the contents of the cyst did not change,
      Echinococcus titers remained unchanged, and the cyst classification remained CE1.

PMID- 15996889
TI  - Subjective and objective descriptors of clinical lumbar spine instability: a
      Delphi study.
AB  - Accurate ability to diagnose lumbar spine clinical instability is controversial
      for numerous reasons, including inaccuracy and limitations in capabilities of
      radiographic findings, poor reliability and validity of clinical special tests,
      and poor correlation between spinal motion and severity of symptoms. It has been
      suggested that common subjective and objective identifiers are specific to lumbar
      spine clinical instability. The purpose of this study was to determine if
      consensual, specific identifiers for subjective and objective lumbar spine
      clinical instability exist as determined by a Delphi survey instrument. One
      hundred and sixty eight physical therapists identified as Orthopaedic Clinical
      Specialists (OCS) or Fellows of the American Academy of Orthopaedic Manual
      Physical Therapists participated in three Delphi rounds designed to select
      specific identifiers for lumbar spine clinical instability. Round I consisted of
      open-ended questions designed to provide any relevant issues. Round II allowed
      the participants to rank the organized findings of Round I. Round III provided an
      opportunity to rescore the ranked variables after viewing other participant's
      results. The results suggest that those identifiers selected by the Delphi
      experts are synonymous with those represented in related spine instability
      literature and may be beneficial for use during clinical differential diagnosis.

PMID- 15996890
TI  - A comparison of symptomatic and asymptomatic office workers performing monotonous
      keyboard work--2: neck and shoulder kinematics.
AB  - Prolonged static posture has been identified as a major risk factor for work
      related neck and upper limb disorders (WRNULD) in computer users. Previous
      research has mainly examined working postures in healthy pain-free individuals.
      The present study examined whether symptomatic subjects exhibited the same
      kinematic patterns as asymptomatic controls during a prolonged computer task. In
      a Case-Control comparison, female office workers performed the same computer task
      using the same adjustable computer workstation for 1h. Three-dimensional (3D)
      kinematics were measured in the head-neck, thorax and shoulder (upper arm)
      segments. Case Group subjects (n=21) displayed trends for increased head-neck
      flexion angles and greater ranges of movements than the Control Group (n=17).
      There were also small but significant differences between groups in side flexion
      and rotation angles of the head-neck region. The shoulder joints displayed
      significantly greater flexion and abduction angles on the right in both groups,
      although no group differences were observed. The increased neck flexion angles
      were associated with significantly higher activity in the upper trapezius muscle
      and with neck and shoulder discomfort. The individual differences in postural
      habits appeared to be independent of the physical environment. These results
      suggest motor control changes are associated with the presence of WRNULD.

PMID- 15996891
TI  - Cell biology of IL-7, a key lymphotrophin.
AB  - IL-7 is essential for the development and survival of T lymphocytes. This review
      is primarily from the perspective of the cell biology of the responding T cell.
      Beginning with IL-7 receptor structure and regulation, the major signaling
      pathways appear to be via PI3K and Stat5, although the requirement for either has
      yet to be verified by published knockout experiments. The proliferation pathway
      induced by IL-7 differs from conventional growth factors and is primarily through
      posttranslational regulation of p27, a Cdk inhibitor, and Cdc25a, a Cdk
      activating phosphatase. The survival function of IL-7 is largely through
      maintaining a favorable balance of bcl-2 family members including Bcl-2 itself
      and Mcl-1 on the positive side, and Bax, Bad and Bim on the negative side. There
      are also some remarkable metabolic effects of IL-7 withdrawal. Studies of IL-7
      receptor signaling have yet to turn up unique pathways, despite the unique
      requirement for IL-7 in T cell biology. There remain significant questions
      regarding IL-7 production and the major producing cells have yet to be fully
      characterized.

PMID- 15996893
TI  - Interval change analysis to improve computer aided detection in mammography.
AB  - We are developing computer aided diagnosis (CAD) techniques to study interval
      changes between two consecutive mammographic screening rounds. We have previously
      developed methods for the detection of malignant masses based on features
      extracted from single mammographic views. The goal of the present work was to
      improve our detection method by including temporal information in the CAD
      program. Toward this goal, we have developed a regional registration technique.
      This technique links a suspicious location on the current mammogram with a
      corresponding location on the prior mammogram. The novelty of our method is that
      the search for correspondence is done in feature space. This has the advantage
      that very small lesions and architectural distortions may be found as well.
      Following the linking process several features are calculated for the current and
      prior region. Temporal features are obtained by combining the feature values from
      both regions. We evaluated the detection performance with and without the use of
      temporal features on a data set containing 2873 temporal film pairs from 938
      patients. There were 589 cases in which the current mammogram contained exactly
      one malignant mass. Cross validation was used to partition the data set into a
      train set and a test set. The train set was used for feature selection and
      classifier training, the test set for classifier evaluation. FROC (free response
      operating characteristic) analysis showed an improvement in detection performance
      with the use of temporal features.

PMID- 15996892
TI  - Silent chemoattractant receptors: D6 as a decoy and scavenger receptor for
      inflammatory CC chemokines.
AB  - The chemokine system includes at least three "silent" receptors, DARC, D6 and CCX
      CKR, with distinct specificity and tissue distribution. D6 binds most
      inflammatory, but not homeostatic, CC chemokines and shuttles in a ligand
      independent way from the plasma membrane to endocytic compartments where
      chemokines are targeted to degradation. In vitro and in vivo evidence, including
      results with gene-targeted mice, is consistent with the view that D6 acts as a
      decoy and scavenger for inflammatory CC chemokines. Thus, D6 has unique
      functional and structural features, which make it ideally adapted to act as a
      chemokine decoy and scavenger receptor, strategically located on lymphatic
      endothelium to dampen inflammation in tissues and draining lymph nodes.

PMID- 15996894
TI  - The complex interplay between mosquito positive and negative regulators of
      Plasmodium development.
AB  - The malaria parasite, Plasmodium, requires sexual development in the mosquito
      before it can be transmitted to the vertebrate host. Mosquito genes are able to
      substantially modulate this process, which can result in major decreases in
      parasite numbers. Even in susceptible mosquitoes, haemolymph proteins implicated
      in systemic immune reactions, together with local epithelial responses, cause
      lysis of more than 80% of the ookinetes that cross the mosquito midgut. In a
      refractory mosquito strain, immune responses lead to melanisation of virtually
      all parasites. Conversely, certain mosquito genes have an opposite effect: they
      are used by the parasite to evade defence reactions. Detailed understanding of
      the interplay between positive and negative regulators of parasite development
      could lead to the generation of novel approaches for malaria control through the
      vector.

PMID- 15996895
TI  - A yeast by any other name: Candida glabrata and its interaction with the host.
AB  - Well-characterized traits important to Candida albicans virulence, such as hyphal
      formation or secreted proteinase activity, play no known role in Candida glabrata
      virulence. Likewise, some C. glabrata characteristics, such as chromatin-based
      regulation of the large telomeric family of lectins encoded by the EPA
      (epithelial adhesin) genes, have no precise parallels in C. albicans. However,
      similarities between the two species, for example in population structure, in the
      large numbers of (putative) adhesins that they encode, and in phenotypic
      plasticity conferred by phenotypic switching, suggest that they share general
      strategies in adaptation to an opportunistic lifestyle.

PMID- 15996896
TI  - Hormone replacement therapy: one-year follow up of DNA damage.
AB  - Although hormone replacement therapy (HRT) may offer considerable benefits for
      menopausal women, the potential cancer risk may limit its use. This work aimed at
      assessing whether HRT is able to induce DNA damage in postmenopausal women
      monitored by the micronucleus (MN) test, which provides a reliable biomarker of
      genotoxicity and cancer risk assessment. A group of 16 healthy women (non
      smokers) in spontaneous menopause were given oral estradiol (2 mg oral micronized
      17-beta estradiol daily) for 1 month, followed by a 30-day wash-out period and a
      transdermal treatment with 17-beta estradiol (1.5 mg gel daily) during 1 month.
      Oral intake of dihydrogesterone (10 mg/day for 12 days/month) was cyclically
      combined with oral or transdermal estradiol during the next 9 months. Venous
      blood samples were collected before the treatment, and after 1, 3, 6 and 12
      months of therapy. Slides were scored blind and MN frequency was evaluated as
      number of micronuclei per 1000 binucleated cells. The baseline plasma levels of
      follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2)
      were simultaneously measured. The means of MN frequency were 18.2+/-1.6, 18.6+/
      2.1, 14.8+/-1.5, 15.9+/-1.0 and 17.7+/-1.3 for samples collected before and at 1,
      3, 6 and 12 months, respectively. The MN frequencies at every sampling time did
      not statistically differ from the basal values. In addition, no statistically
      significant associations between MN values and hormone levels of E2 and FSH were
      observed throughout the entire study. This study shows the absence of any
      significant increase of MN frequencies in women undergoing oral and/or
      transdermal HRT, sequentially monitored for up to 12 months of therapy.

PMID- 15996897
TI  - Optimizing principal components analysis of event-related potentials: matrix
      type, factor loading weighting, extraction, and rotations.
AB  - OBJECTIVE: Given conflicting recommendations in the literature, this report seeks
      to present a standard protocol for applying principal components analysis (PCA)
      to event-related potential (ERP) datasets. METHODS: The effects of a covariance
      versus a correlation matrix, Kaiser normalization vs. covariance loadings,
      truncated versus unrestricted solutions, and Varimax versus Promax rotations were
      tested on 100 simulation datasets. Also, whether the effects of these parameters
      are mediated by component size was examined. RESULTS: Parameters were evaluated
      according to time course reconstruction, source localization results, and
      misallocation of ANOVA effects. Correlation matrices resulted in dramatic
      misallocation of variance. The Promax rotation yielded much more accurate results
      than Varimax rotation. Covariance loadings were inferior to Kaiser Normalization
      and unweighted loadings. CONCLUSIONS: Based on the current simulation of two
      components, the evidence supports the use of a covariance matrix, Kaiser
      normalization, and Promax rotation. When these parameters are used, unrestricted
      solutions did not materially improve the results. We argue against their use.
      Results also suggest that optimized PCA procedures can measurably improve source
      localization results. SIGNIFICANCE: Continued development of PCA procedures can
      improve the results when PCA is applied to ERP datasets.

PMID- 15996898
TI  - Fatigue in the executive cortical network demonstrated in narcoleptics using
      functional magnetic resonance imaging--a preliminary study.
AB  - BACKGROUND AND PURPOSE: To demonstrate dynamic changes in cerebral functional
      activation during a working memory task in a state of severe excessive daytime
      sleepiness. PATIENTS AND METHODS: Omitting the usual morning dose of stimulants
      in three narcoleptics induced sleepiness. Functional magnetic resonance imaging
      (fMRI) was used to map cerebral activation during the performance of a 2-back
      verbal working memory task. Repeated 9.5 min scans were performed, until the
      subjects felt they could not continue. This was the functional imaging equivalent
      of the maintenance of wakefulness test. RESULTS: Bilateral and widespread
      activation in known nodes of the executive network were seen during the first
      scan in all subjects, including the lateral prefrontal, posterior parietal and
      anterior cingulate cortex. There was a reduction in cerebral activation,
      especially but not exclusively in the prefrontal cortex, associated with slowing
      of performance from the first to the last tolerated scan. On stimulants,
      subjective alertness, activation and objective performance were readily
      maintained. CONCLUSION: This preliminary study suggests that fatigue in the
      executive cortical network may be demonstrated by a progressive reduction in
      regional cerebral activation across scans, which may be prevented by stimulant
      use. Averaging multiple scan runs, a typical practice in fMRI, could blur
      important dynamic components of activation.

PMID- 15996899
TI  - Two cases of endomyocardial disease with hypereosinophilia in Turkey.
AB  - Endomyocardial disease is characterized by fibrothrombotic thickening of apical
      endocardium and subvalvular regions of atrioventricular valves. The disease is
      uncommon in Turkey. In this report two cases of endomyocardial disease with
      hypereosinophilia which were medically managed are presented.

PMID- 15996900
TI  - The influence of sulindac on diabetic cardiomyopathy: a non-invasive evaluation
      by Doppler echocardiography in streptozotocin-induced diabetic rats.
AB  - The aim of the present study was to investigate the cardioprotective activity of
      sulindac as an aldose reductase inhibitor in the development of cardiomyopathy by
      non-invasive techniques; M-mode and Doppler echocardiography. Diabetes was
      induced by streptozotocin (45 mg/kg, iv) in the Sprague-Dawley rats.
      Echocardiography, biochemical and histological studies were carried out in normal
      control, diabetic untreated, diabetic vehicle (sodium carboxy methyl cellulose,
      1%, po) and sulindac (6 mg/kg and 20 mg/kg, po) treated animals at varying time
      intervals. In the diabetic untreated and vehicle treated rats at 12 weeks after
      induction of diabetes, there was a significant decrease in the E-wave, an
      increase in the A-wave and corresponding decrease in the E/A ratio was observed.
      Significant decrease in the Eat was found after 12 weeks (P < 0.05). Whereas
      systolic function variables; ejection fraction and fractional shortening were
      significantly decreased (P < 0.05) after 12 weeks compared to their baseline
      data. In the sulindac treated animals, there were no significant alterations in
      the systolic and diastolic parameters were found throughout the study period.
      Myocardial fructose levels were significantly increased in the diabetic untreated
      animals compared to normal control rats (P < 0.05), whereas these were
      significantly decreased in the sulindac (6 mg/kg and 20 mg/kg) treated animals
      (301.11+/-37.98, 214.11+/-25.31, vs. 914.88+/-56.01 nmol/g) compared to diabetic
      vehicle treated group (P < 0.05). Extensive focal ischemic myocyte degeneration
      was observed in the diabetic untreated and vehicle treated rats, whereas in the
      sulindac (6 mg/kg) treated rats, minimal necrosis was found, with no evidence of
      necrosis in sulindac (20 mg/kg) group. Our results show for the first time that
      sulindac has a cardioprotective activity as this agent prevented the development
      of left ventricular dysfunction in STZ-induced diabetic rats in the 12-week
      chronic study.

PMID- 15996901
TI  - Effects of intermittent hypoxia on sympathetic activity and blood pressure in
      humans.
AB  - Sympathetic nerve activity and arterial pressure are frequently elevated in
      patients with obstructive sleep apnea (OSA). The mechanisms responsible for
      chronic sympathetic activation and hypertension in OSA are unknown. To determine
      whether repetitive apneas raise sympathetic nerve activity and/or arterial
      pressure, awake and healthy young subjects performed voluntary end-expiratory
      apneas for 20 s per min for 30 min (room air apneas). To accentuate intermittent
      hypoxia, in a separate group of subjects, hypoxic gas (inspired O2 10%) was added
      to the inspiratory port for 20 s before each apnea (hypoxic apneas). Mean
      arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA, peroneal
      microneurography) were determined before and up to 30 min following the
      repetitive apneas. Following 30 hypoxic apneas (O2 saturation nadir 83.1+/-1.2%),
      MSNA increased from 17.4+/-2.7 to 23.4+/-2.5 bursts/min and from 164+/-28 to
      240+/-35 arbitrary units respectively (P<0.01 for both; n=10) and remained
      elevated while MAP increased transiently from 80.5+/-3.7 to 83.1+/-3.9 mm Hg
      (P<0.05; n=11). In contrast, in the subjects who performed repetitive apneas
      during room air exposure (O2 saturation nadir 95.1+/-0.8%), MAP and MSNA did not
      change (n=8). End-tidal CO2 post-apnea, an index of apnea-induced hypercapnia,
      was similar in the 2 groups. In a separate control group, no effect of time on
      MAP or MSNA was noted (n=7). Thus, repetitive hypoxic apneas result in sustained
      sympathetic activation and a transient elevation of blood pressure. These effects
      appear to be due to intermittent hypoxia and may play a role in the sympathetic
      activation and hypertension in OSA.

PMID- 15996902
TI  - Corticotropin-releasing factor-binding protein, stress and major depression.
AB  - Major depressive disorder (MDD) is characterized by a dysregulation of the stress
      response system. A corticotropin-releasing factor (CRF) hyperdrive is a
      consistent and well-documented finding. CRF-binding protein (CRF-BP) may play a
      role in the pathogenesis of MDD. CRF-BP reduces the availability of CRF by
      binding free CRF and inhibits CRF function at the pituitary level. Moreover, CRF
      BP expression increases in the pituitary and amygdala in response to acute
      stress, providing an additional feedback mechanism to maintain the homeostasis of
      the stress response. There are different regulatory elements of the expression of
      CRF-BP gene that are implicated in the pathophysiology of MDD, including CRF,
      glucocorticoids, cytokines and estrogens. A specific haplotype within the CRF-BP
      gene has been associated with MDD, but confirmation of this finding is necessary.
      Currently, the possible role of CRF-BP in the pathophysiology of conditions that
      have been associated with a hypofunction of the CRF system and immune
      dysfunctions is unclear. Implications of the function of CRF-BP for therapeutic
      strategies in MDD are being discussed. An important advantage of ligands that
      target CRF-BP is that concentrations of free CRF can be altered without acting
      directly on the transmission of CRF through its receptor.

PMID- 15996903
TI  - Lack of consensus gene expression changes associated with radiation-induced
      chromosomal instability.
AB  - The relatively high frequency with which ionizing radiation induces genomic
      instability suggests that a gene mutation occurring after irradiation is an
      unlikely cause of the phenotype. To search for mechanism(s) of initiation and
      perpetuation of this instability phenotype, gene expression profiles of clones
      exhibiting delayed chromosomal instability were analyzed. Microarray analysis
      using two pools of isogenic radiation-induced chromosomally unstable clones
      compared to an irradiated but chromosomally stable clone uncovered a set of 68
      differentially expressed genes using two methods of analysis. Unexpectedly, all
      68 genes were under-expressed relative to the chromosomally stable reference
      clone. Further analysis of the candidates placed the differentially expressed
      genes into pathways implicating differential MAP kinase signaling,
      ubiquitin/proteasome function, DNA repair, cell cycle control, lipid signaling,
      nucleotide metabolism, and other potentially disrupted pathways. Validation
      studies using northern and western blotting, and functional assays concluded that
      although differences in some of these pathways exist, no single gene or molecular
      pathway was found to be differentially regulated in all of the chromosomally
      unstable clones tested. Inferred from these data is that there are multiple
      potential molecular pathways and/or events that maintain the unstable phenotype,
      and no single expression pattern is linked to instability in the unstable clones
      analyzed.

PMID- 15996904
TI  - The yeast rDNA locus: a model system to study DNA repair in chromatin.
AB  - Most of the studies on the effect of chromatin structure and chromatin remodeling
      on DNA repair are based on in vitro reconstituted assays. In such experiments
      individual nucleosomes are either released by nuclease digestion of native
      chromatin fibers or are assembled from purified histones. Though reconstituted
      assays are valid approaches to follow NER in chromatin they are of somehow
      limited physiological relevance since single core particles do not exist in vivo
      [K. van Holde, J. Zlatanova, The nucleosome core particle: does it have
      structural and physiological relevance? Bioessays 21 (1999) 776-778]. This is
      particularly true for studies involving core histones tails, as in their natural
      chromatin context histones tails participate in interactions that are not
      necessarily present in vitro [J.C. Hansen, C. Tse, A.P. Wolffe, Structure and
      function of the core histone N-termini: more than meets the eye, Biochemistry 37
      (1998) 17637-17641; J.J. Hayes, J.C. Hansen, Nucleosomes and chromatin fiber,
      Curr. Opin. Genet. Dev. 11 (2001) 124-129]. Indeed it was found that human DNA
      ligase I has the capability to ligate a nick on the surface of a 215bp nucleosome
      but not a nick in a nucleosome lacking linker DNA, possibly because of forced
      interactions between histone tails and core DNA present in the latter complex
      [D.R. Chafin, J.M. Vitolo, L.A. Henricksen, B.A. Bambara, J.J. Hayes, Human DNA
      ligase I efficiently seals nicks in nucleosomes, EMBO J. 19 (2000) 5492-5501]. In
      addition, chromatin remodeling could also occur in the higher ordered folding of
      chromatin and involve multiple arrays of nucleosomes [P.J. Horn, C.L. Peterson,
      Chromatin higher order folding: wrapping up transcription, Science 297 (2002)
      1824-1827]. By studying the chromatin structure of ribosomal genes in yeast, our
      knowledge of the fate of nucleosomes during transcription and DNA replication has
      improved considerably [R. Lucchini, J.M. Sogo, The dynamic structure of ribosomal
      RNA gene chromatin, in: M.R. Paule (Ed.), Transcription of Ribosomal RNA Genes by
      Eukaryotic RNA Polymerase I, Springer-Verlag/R.G. Landes Company, 1998, pp. 254
      276]. How nuclear processes such as DNA repair take place in chromatin is still
      largely unknown, and in this review I discuss how the yeast rDNA locus may be
      exploited to investigate DNA repair and chromatin modification in vivo.

PMID- 15996905
TI  - Disease modifying genes in cystic fibrosis.
AB  - The variation in cystic fibrosis (CF) lung disease and development of CF related
      complications correlates poorly with the genotype of the CF transmembrane
      regulator (CFTR) and with environmental factors. Increasing evidence suggests
      that phenotypic variation in CF can be attributed to genetic variation in genes
      other than the CFTR gene, so-called modifier genes. In recent years, multiple
      candidate modifier genes have been investigated in CF, especially genes that are
      involved in the control of infection, immunity and inflammation. Some of these
      genes have been rather conclusively identified as modifiers of the CF phenotype,
      whereas associations found in other genes have not been confirmed or are
      conflicting. Identification of genetic variation in modifier genes, obtained by
      genotype-phenotype studies in well-defined patient populations, may be used as an
      aid to prognosis and may provide the possibility of new therapeutic
      interventions.

PMID- 15996906
TI  - Contributions of lower limb and abdominal compression to ventilation
      inhomogeneity in hypergravity.
AB  - Gravito-inertial load in the head-to-foot direction (Gz) and compression of the
      lower body half by an anti-G suit (AGS) are both known to influence ventilation
      distribution in the lungs. To study the interaction of Gz and AGS and to asses
      the separate contributions from lower limbs and abdominal compressions to large
      and small-scale ventilation inhomogeneities nine males performed SF6/He vital
      capacity (VC) single-breath washouts at 1, 2, and 3 Gz in a centrifuge, with
      abdominal and/or lower limbs compressions. SF6/He and (SF6-He) phase III slopes
      were used for determination of overall and small-scale ventilation inhomogeneity.
      Closing volume and phase IV height were used as measures of large-scale
      inhomogeneity. VC decreased marginally with G-load but markedly with lower limbs
      compression. Small-scale ventilation inhomogeneity increased slightly with G
      load, but substantially with AGS pressurization. Small-scale ventilation
      inhomogeneity increased with AGS pressurization. Large-scale inhomogeneity
      increased markedly with G-load. Translocation of blood to the lungs might be the
      key determinant for changes in small-scale ventilation inhomogeneity when
      pressurizing an AGS.

PMID- 15996907
TI  - Hypersensitivity of pulmonary chemoreflex induced by poly-L-lysine: role of
      cationic charge.
AB  - This study was carried out to investigate the role of cationic charge in the
      hypersensitivity of pulmonary C-fibers induced by airway exposure to synthetic
      cationic protein poly-L-lysine (PLL) in anesthetized rats. Inhalation of PLL
      aerosol induced a distinctly irregular breathing pattern, and significantly
      enhanced the pulmonary chemoreflex responses to capsaicin. However, after the
      cationic charges were completely removed from PLL by succinylation, the
      succinylated PLL no longer produced any change in either the baseline breathing
      pattern or the reflex responses to capsaicin. In addition, the effects of PLL
      were also abolished after premixing it with a polyanion, poly-L-glutamic or poly
      L-aspartic acid, before delivery. In sharp contrast, when delivered within 5 min
      after the PLL aerosol, these two polyanions were completely ineffective in
      reversing the effects of PLL. Electrophysiological recording of the afferent
      activity of single pulmonary C-fibers further supported our conclusion that the
      cationic charge carried by this protein is primarily responsible for generating
      the stimulatory and sensitizing effects of PLL on these afferents.

PMID- 15996908
TI  - On-column preconcentration of glutathione and glutathione disulfide using pH
      mediated base stacking for the analysis of microdialysis samples by capillary
      electrophoresis.
AB  - Capillary electrophoresis (CE) has become a useful analytical tool for the
      analysis of microdialysis samples. However, CE with UV detection (CE-UV) does not
      provide detection limits sufficient to quantify glutathione (GSH) and glutathione
      disulfide (GSSG) in biological samples such as liver microdialysates, because of
      the small optical path length in the capillary. To overcome this limitation, an
      on-column preconcentration technique, pH-mediated base stacking, was used in this
      study to improve the sensitivity of CE-UV. This stacking technique allowed large
      volumes of high ionic strength sample injection without deterioration of the
      separation efficiency and resolution. A 26-fold increase in sensitivity was
      achieved for both GSH and GSSG using the pH-mediated base stacking, relative to
      normal injection without stacking. The limit of detection for GSH and GSSG was
      found to be 0.75 microM (S/N=6) and 0.25 microM (S/N=6), respectively. The
      developed method was used to analyze GSH and GSSG in liver microdialysates of
      anesthetized Sprague Dawley male rats. The basal concentrations of GSH and GSSG
      in the liver microdialysates of male rats were found to be 4.73+/-2.08 microM
      (n=7) and 5.52+/-3.66 microM (n=7), respectively.

PMID- 15996909
TI  - The study of fingerprint characteristics of the emanations from human arm skin
      using the original sampling system by SPME-GC/MS.
AB  - An efficient and noninvasive method consisting of an original sampling device,
      solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC
      MS) was developed to analyze volatile organic emanations from the skin of human
      arms. The emanations were sampled by SPME connected with the active sampling
      device for 30 min and transferred into GC-MS immediately for the consequent
      analysis. The sampling projects for 15 candidates were scheduled in both winter
      and spring with the same optimized conditions. Thirty-five compounds were finally
      identified according to various degrees of certainty. Different emission
      behaviors specified with principal component analysis (PCA) and similar
      fingerprint characteristics were observed clearly by comparisons of chromatograms
      of different seasons. Top ten emanations contributing to characteristics in
      different seasons were attempted to be described using comparisons based on
      common model strategy. The large amounts of experimental data were all handled by
      the corresponding chemometrics strategies with the homemade chromatographic data
      processing system. The results suggest that the analysis based on fingerprint
      characteristics of human skin emanations could provide useful and important clues
      to reveal biomarkers among the mixture of human skin emanations.

PMID- 15996910
TI  - High-performance liquid chromatography of nalbuphine, butorphanol and morphine in
      blood and brain microdialysate samples: application to
      pharmacokinetic/pharmacodynamic studies in rats.
AB  - A rapid and sensitive assay for quantification of nalbuphine, butorphanol and
      morphine in blood (50 microL) and brain microdialysate ( approximately 40 microL)
      samples was developed. Blood samples were extracted with ethyl acetate. Analysis
      was performed with high-performance liquid chromatography (HPLC) coupled to an
      electrochemical detector. The mobile phase was a mixture of 0.1 M sodium
      phosphate buffer, methanol and octane-sulfonic acid with ratio and pH depending
      on compound and matrix. The limits of quantification in blood samples were 25, 50
      and 25 ng/mL for nalbuphine, butorphanol and morphine, respectively and 0.5 ng/mL
      for morphine in microdialysate samples. Based on sample volume, sensitivity and
      reproducibility, these assays are particularly suitable for
      pharmacokinetic/pharmacodynamic studies in rodents.

PMID- 15996911
TI  - Crystallization and preliminary crystallographic studies of the recombinant
      antitumour lectin from the edible mushroom Agrocybe aegerita.
AB  - The antitumour lectin from Agrocybe aegerita, named AAL, shows strong inhibition
      effects on human and mouse tumour cells via apoptosis induction activity.
      Recombinant AAL (rAAL) has been expressed and purified. Both rAAL and rAAL
      lactose complex have been crystallized and their X-ray diffraction data were
      collected to resolutions of 1.9 A and 1.6 A, respectively. Both crystals belong
      to space group P2(1) with unit cell parameters a = 53.20 A, b = 66.01 A, c =
      57.86 A, beta = 109.38 and a = 53.38 A, b = 66.29 A, c = 58.02 A, beta = 109.03,
      respectively.

PMID- 15996912
TI  - Application of the platelet count/spleen diameter ratio to rule out the presence
      of oesophageal varices in patients with cirrhosis: a validation study based on
      follow-up.
AB  - BACKGROUND: Screening for oesophageal varices represents an important part of the
      diagnostic work-up of cirrhotic patients. We have previously shown that the
      platelet count/spleen diameter ratio is a parameter that can rule out the
      presence of oesophageal varices safely and in a cost-effective fashion. AIM: To
      evaluate the prognostic and diagnostic accuracy of the platelet count/spleen
      diameter ratio for ruling out the presence of oesophageal varices in the follow
      up of a cohort of cirrhotic patients without oesophageal varices at inclusion.
      METHODS: After initial endoscopy, the 106 cirrhotic patients without oesophageal
      varices who participated in our previous study were followed-up with annual or
      biannual surveillance endoscopy. Patients were censored at the time of diagnosis
      of oesophageal varices or at their last visit, and at that time platelet count
      and spleen diameter were recorded. Sixty-eight patients made up the study cohort
      after excluding patients who were lost to follow-up or died before undergoing
      control endoscopy. RESULTS: During the follow-up, 27 patients (40%) developed
      oesophageal varices. Patients with higher baseline platelet count/spleen diameter
      ratios (p<0.0001) as well as a ratio above 909 were less likely to develop
      oesophageal varices (p<0.0005). At follow-up, a platelet count/spleen diameter
      ratio < or = 909 had 100% negative predictive value and 84% efficiency in
      identifying the presence of oesophageal varices. CONCLUSIONS: The use of the
      platelet count/spleen diameter ratio proved to be an effective means for ruling
      out the presence of oesophageal varices even in the longitudinal follow-up of
      patients.

PMID- 15996913
TI  - Dual X-ray absorptiometry (DXA) of the lumbar spine in a clinical paediatric
      setting: does the method of size-adjustment matter?
AB  - Dual X-ray absorptiometry (DXA) is increasingly used in a clinical setting to
      evaluate bone mass in children. Areal Bone Mineral Density (aBMD) measurements
      are known to be influenced by body size, but there is no consensus on the optimal
      way to deal with this for individual patients. AIM: To compare parameters of bone
      mass with varying degrees of size correction and to determine the effect on the
      categorisation of patients as normal or abnormal. SUBJECTS AND METHODS: Healthy
      children (n = 78) and 4 groups of patients (n = 194) underwent DXA scans of the
      lumbar spine (L2-4, GE Lunar Prodigy). Five measures of bone mass were derived,
      all adjusted for age and sex: aBMD, BMAD (BMC/BA (1.5)), BMCh (BMC/height3), BMCa
      (BMC adjusted for BA), BMCt (BMC adjusted for BA and height). SD scores were
      calculated for each parameter for patients using data from healthy controls.
      RESULTS: Compared to healthy children, all patient groups had significantly
      reduced BMD SD scores (P < 0.001). Mean BMAD, BMCa and BMCt SD scores were
      significantly lower in only 2/4 patient groups, whilst BMCh SD scores were low
      only in one group. BMCt showed no advantage over BMCa. The proportion of patients
      with SD scores <-2 was 27% for aBMD but between 10-13% for BMAD, BMCh and BMCa.
      CONCLUSIONS: All size-corrected parameters of bone mass performed similarly and
      classified significantly fewer patients as abnormal than did aBMD. The use of one
      of these parameters should reduce the number of patients diagnosed
      inappropriately with 'low bone mass'. However, without validation against an
      outcome measure or 'gold standard' of bone density or structure, it is not
      possible to determine which parameter is most correct.

PMID- 15996914
TI  - Long awaited: CD34+ determination in steady-state hematopoiesis by real-time
      polymerase chain reaction.

PMID- 15996915
TI  - MLL-PTD as a marker for minimal residual disease studies: quantification counts.

PMID- 15996916
TI  - A leukemia-enriched cDNA microarray platform identifies new transcripts with
      relevance to the biology of leukemias.

PMID- 15996917
TI  - ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B
      lineage acute lymphoblastic leukemia cells.

PMID- 15996918
TI  - Molecular characteristics and gene segment usage in IGH gene rearrangements in
      multiple myeloma.

PMID- 15996919
TI  - Type 1 and type 2 T cells profile in idiopathic thrombocytopenic purpura.

PMID- 15996920
TI  - The Malmo International Brother Study (MIBS). Genetic defects and inhibitor
      development in siblings with severe hemophilia A.

PMID- 15996921
TI  - Rabbit-IgG levels in patients receiving thymoglobulin as part of conditioning
      before unrelated donor stem cell transplantation.

PMID- 15996922
TI  - Prognostic factors identifiable at the time of onset of acute graft-versus-host
      disease after allogeneic hematopoietic cell transplantation.

PMID- 15996923
TI  - Gain of function, loss of control - a molecular basis for chronic
      myeloproliferative disorders.

PMID- 15996924
TI  - Progenitor cell trafficking in physiologic conditions and in myeloproliferative
      diseases: quantification of CD34+ cells by polymerase chain reaction.
AB  - BACKGROUND AND OBJECTIVES: Previous studies using flow cytometry have shown that
      CD34+ cell trafficking is increased in patients with chronic idiopathic
      myelofibrosis. Few data exist on physiologic CD34 + cell trafficking and the
      quantification of very low cell ranges requires reliable and sensitive
      measurement techniques. The aim of this study was to establish a quantitative
      polymerase chain reaction (PCR) technique for studying CD34+ cell trafficking in
      physiologic conditions, and in patients with myeloproliferative diseases. DESIGN
      AND METHODS: CD34+ cell trafficking was measured in 56 controls [(healthy
      controls (n=21), patients with ischemic cardiopathy (n=21), patients with
      secondary thrombocytosis or erythrocytosis (n=14)], and in 37 untreated patients
      with myeloproliferative diseases diagnosed according to the WHO-criteria
      [(essential thrombocythemia (n=10), polycythemia vera (n=14) and chronic
      idiopathic myelofibrosis (n=13)]. Quantitative PCR was used to determine CD34
      mRNA expression in peripheral blood samples. RESULTS: Physiologic CD34 mRNA
      expression ranges were determined in the healthy control group. Mean CD34 mRNA
      expression was within the physiologic range in patients with ischemic
      cardiopathy, secondary thrombocytosis or erythrocytosis, essential
      thrombocythemia and polycythemia vera (p=0.146), but was significantly increased
      in patients with chronic idiopathic myelofibrosis (p<0.001). When analyzed
      individually, 12/13 patients with chronic idiopathic myelofibrosis and 3/14
      patients with polycythemia vera showed CD34 mRNA expression above the physiologic
      range. INTERPRETATION AND CONCLUSIONS: This is a first report about CD34+ cell
      trafficking measured by quantitative PCR. Quantitative PCR is a reliable method
      suitable for the quantification of very low cell populations. Our study confirms
      the significant increase of CD34+ cell trafficking in patients with chronic
      idiopathic myelofibrosis, and in a subset of patients with polycythemia vera.
      Prospective studies are underway to characterize these circulating CD34+ cells
      and to investigate their role in the pathophysiology of myeloproliferative
      diseases.

PMID- 15996925
TI  - Risk assessment by monitoring expression levels of partial tandem duplications in
      the MLL gene in acute myeloid leukemia during therapy.
AB  - BACKGROUND AND OBJECTIVES: A partial tandem duplication within the MLL-gene (MLL
      PTD) can be found in 8% of all patients with karyotypically normal acute myeloid
      leukemia (AML), a group in which polymerase chain reaction-(PCR) based minimal
      residual disease analysis has not, so far, been possible. DESIGN AND METHODS: A
      sensitive real-time PCR assay to quantify MLL-PTD transcripts was established and
      expression ratios assessed in diagnostic and follow-up samples. The prognostic
      significance of MLL-PTD expression levels was evaluated in 145 MLL-PTD positive
      patients at diagnosis and in 44 patients during and after treatment. RESULTS:
      Paired samples from 16 patients evaluated at diagnosis and relapse for the
      presence of the MLL-PTD were analyzed in parallel and all samples were positive
      at both time points. Overall, 173 samples from 44 patients were analyzed during
      follow-up (median sample number: 4/patient (range 2-17)). Nineteen patients were
      evaluable for MRD within the first 2 months, 15 patients within 4 months, and 19
      patients within 6 months after the start of therapy. A >or= 2 log reduction of
      MLL-PTD expression in comparison to < 2 log reduction within 2, 4, and 6 months
      after start of therapy was found to be significantly associated with longer
      overall survival (p=0.029, p=0.007, and p=0.022, respectively). A molecular
      relapse was detected in 2 cases, in each case preceeding clinical manifestation
      by 35 days. INTERPRETATION AND CONCLUSIONS: These data suggest that MLL-PTD is a
      stable marker and can be used as a prognostically important marker of MRD in
      patients with karyotypically normal AML.

PMID- 15996926
TI  - A leukemia-enriched cDNA microarray platform identifies new transcripts with
      relevance to the biology of pediatric acute lymphoblastic leukemia.
AB  - BACKGROUND AND OBJECTIVES: Microarray gene expression profiling has been widely
      applied to characterize hematologic malignancies, has attributed a molecular
      signature to leukemia subclasses and has allowed new subclasses to be
      distinguished. We set out to use microarray technology to identify novel genes
      relevant for leukemogenesis. To this end we used a unique leukemia-enriched cDNA
      microarray platform. DESIGN AND METHODS: The systematic sequencing of cDNA
      libraries of normal and leukemic bone marrow allowed us to increase the number of
      genes to yield a new release of a previously generated cDNA microarray. Using
      this platform we analyzed the expression profiles of 4,670 genes in bone marrow
      samples from 18 pediatric patients with acute lymphoblastic leukemia (ALL).
      RESULTS: Expression profiling consistently distinguished the leukemia patients
      into three groups, those with T-ALL, B-ALL and B-ALL with MLL/AF4 rearrangement,
      in agreement with the clinical classification. Our platform identified 30 genes
      that best discriminate these three subtypes. Using mini-array technology these 30
      genes were validated in another cohort of 17 patients. In particular we
      identified two novel genes not previously reported: endomucin (EMCN) and
      ubiquitin specific protease 33 (USP33) that appear to be over-expressed in B-ALL
      relative to their expression in T-ALL. INTERPRETATION AND CONCLUSIONS: Microarray
      technology not only allows the distinction between disease subclasses but also
      offers a chance to identify new genes involved in leukemogenesis. Our approach of
      using a unique platform has proven to be fruitful in identifying new genes and we
      suggest exploration of other malignancies using this approach.

PMID- 15996927
TI  - ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B
      lineage acute lymphoblastic leukemia cells.
AB  - BACKGROUND AND OBJECTIVES: Zeta-associated protein 70 (ZAP-70), a member of the
      Syk family of protein tyrosine kinases, is normally expressed in T and NK cells.
      While little is known about ZAP-70 expression in normal human B cells, it has
      been reported that ZAP-70 is expressed in a subset of patients with chronic
      lymphocytic leukemia (CLL) with a poor prognosis. In this study, we examined the
      expression and phosphorylation status of ZAP-70 in B-lineage acute lymphoblastic
      leukemia (Blin-ALL). DESIGN AND METHODS: First, ZAP-70 protein expression was
      assessed by Western blotting and flow cytometry and ZAP-70 mRNA transcripts were
      analyzed by reverse transcription polymerase chain reaction (RT-PCR) on human
      precursor B cell lines. Experiments were then carried out on cells obtained from
      18 patients with Blin-ALL and from normal human bone marrow. RESULTS: ZAP-70 was
      constitutively expressed and phosphorylated on tyr319 in human precursor Blin-ALL
      cell lines as well as in primary B leukemic cells from all examined Blin-ALL
      patients with pro-B, pre-B and B phenotypes, but not in malignant myeloid cells.
      Importantly, analysis of normal human bone marrow revealed expression of ZAP-70
      transcripts only in the CD34+ cell fraction (either CD19-CD10- or CD19+CD10+) but
      not in the CD34- cell fraction (CD19+sIgM- pre-B cells or CD19+sIgM+ immature B
      cells). INTERPRETATION AND CONCLUSIONS: ZAP-70 was found to be expressed in the
      CD34+ normal bone marrow compartment including earlier B-cell progenitors, but
      not in CD34- pre-B and immature B cells. By contrast, ZAP-70 was consistently
      expressed and phosphorylated in Blin-ALL cells. Further studies are required to
      determine whether ZAP-70 may play a pathophysiological role in Blin-ALL.

PMID- 15996928
TI  - Molecular characteristics and gene segment usage in IGH gene rearrangements in
      multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: Analysis of IgH rearrangements in B-cell malignancies
      has provided clinical researchers with a wide range of information during the
      last few years. However, only a few studies have contributed to the
      characterization of these features in multiple myeloma (MM), and they have been
      focused on the analysis of the expressed IgH allele only. Comparison between the
      expressed and the non-functional IgH alleles allows further characterizion of the
      selection processes to which pre-myeloma cells are submitted. DESIGN AND METHODS:
      We analyzed a cohort of 84 untreated MM patients in order to characterize their
      functional VDJH and non-functional DJH rearrangements. The pattern of mutations
      and gene segment usage for both types of rearrangements was analyzed by
      polymerase chain reaction and sequencing. RESULTS: VH3 and VH1 family members
      were over- and under-represented, respectively. VH3-30 and VH3-15 segments were
      the most frequently used, whereas VH4-34 was found only in non-functional or
      heavily mutated VDJH rearrangements. DH2 and DH3 family members were over
      represented in both VDJH and DJH repertoires, while the DH1 family was under
      represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2
      21 gene segments were found to be over-represented in the functional repertoire
      while segments commonly used by less mature B-cell malignancies, such as DH6-19
      or DH3-3, were under-represented. INTERPRETATION AND CONCLUSIONS: Data reported
      here help to identify the clonogenic MM cell as a post-germinal center B cell
      that has undergone selection processes during the germinal center reaction.

PMID- 15996929
TI  - Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura.
AB  - BACKGROUND AND OBJECTIVES: Adult idiopathic thrombocytopenic purpura (ITP) is a
      chronic acquired organ-specific autoimmune hemorrhagic disease characterized by
      the production of antibodies against antigens on the membranes of platelet,
      resulting in enhanced Fc-mediated destruction of the platelets by macrophages in
      the reticuloendothelial system. Dysfunctional cellular immunity is considered
      important in the pathophysiology of ITP. The aim of this study was to explore the
      profile of type1 and type2 T cells in chronic ITP patients. DESIGN AND METHODS:
      The balance of Th1/Th2 and Tc1/Tc2 was studied by simultaneous analysis of
      intracellular cytokines of peripheral blood mononuclear cells and splenocytes in
      short-term cultures activated with PMA/ionomycin as well as mRNA expression of T
      bet and GATA-3 in peripheral blood mononuclear cells and splenocytes using real
      time polymerase chain reaction. RESULTS: Patients with active disease but not
      patients in remission had significant higher Th1/Th2 (p<0.01) and Tc1/Tc2
      (p<0.01) ratios in peripheral blood (PB) and significant higher Th1/Th2 ratio in
      splenocytes (p<0.01) than those in the control group. The Tc1/Tc2 ratio in
      splenocytes in ITP patients was higher than that in control, but did not reach
      significant difference (p=0.082). GATA-3 mRNA expression in ITP patients was
      significantly lower both in PB (p<0.01) and in splenocytes (p<0.01) than in
      corresponding samples from controls while there was no difference in T-bet
      expression. INTERPRETATION AND CONCLUSIONS: Our data indicate that ITP is a T1
      cell (Th1 and Tc1) predominant disease although the precise mechanisms await
      further functional assay. The T-bet/GATA-3 ratio may provide a surrogate marker
      of T1/T2 cytokine balance. Shifting the cytokine patterns from T1 to T2 might be
      a potential immunotherapy for ITP.

PMID- 15996930
TI  - The Malmo International Brother Study (MIBS). Genetic defects and inhibitor
      development in siblings with severe hemophilia A.
AB  - BACKGROUND AND OBJECTIVES: The strongest risk factor identified for inhibitor
      development in people with severe hemophilia A is the type of factor VIII gene
      mutation. The objective of this study was to evaluate the mutation type dependent
      concordance rate of inhibitor formation in siblings. DESIGN AND METHODS: The gene
      defect, treatment and inhibitor history were evaluated in 113 families in which
      two or more siblings had severe hemophilia A. RESULTS: Seventy-nine of the
      families (69.9%) were concordant in that either all or none of the siblings had a
      history of inhibitors. The concordance in 59 families with inhibitors was 42.4%.
      The corresponding figures for the 74 families with intron 22 inversion were 63.5%
      and 40.0%, respectively, and the overall concordance within 14 families with
      nonsense mutations was 78.6%. The siblings in two families with large gene
      deletions had no inhibitor history. A small proportion of the families with
      missense mutations, small deletions/insertions and splice site mutations
      developed inhibitors, but in four of the families two or more siblings developed
      high-responding inhibitors. In 18 of the 25 concordant families (72.0%) with
      inhibitors, the inhibitor was also of the same type (high-responding).
      INTERPRETATION AND CONCLUSIONS: This is the first study of the association
      between inhibitor formation and the causative factor VIII gene mutation in
      siblings. The data show that the type of mutation provides, to some extent, the
      basis for this relationship, but the mutation itself is not enough to predict the
      risk for therapy-induced inhibitor formation.

PMID- 15996931
TI  - Rabbit-immunoglobulin G levels in patients receiving thymoglobulin as part of
      conditioning before unrelated donor stem cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: The role of serum concentrations of rabbit
      antithymoglobulin (ATG) in the development of acute graft-versus-host disease
      (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) with
      unrelated donors is unknown. DESIGN AND METHODS: We determined the serum
      concentration of rabbit immunoglobulin-G (IgG) using an enzyme linked
      immunosorbent assay in 61 patients after unrelated donor HSCT. The doses of ATG
      ranged between 4 and 10 mg/kg. The conditioning consisted mainly of
      cyclophosphamide and total body irradiation or busulfan. Most patients received
      GVHD prophylaxis with cyclosporine and methotrexate. RESULTS: The rabbit IgG
      levels varied widely in each dose group. The levels of rabbit IgG gradually
      declined and could still be detected up to five weeks after HSCT. We found a
      correlation between the grade of acute GVHD and the concentration of rabbit IgG
      in serum before the transplantation (p=0.017). Patients with serum levels of
      rabbit IgG >70 mg/mL before HSCT ran a very low risk of developing acute GVHD
      grades II-IV, as compared to those with levels <70 mg/mL (11% vs. 48%, p=0.006).
      INTERPRETATION AND CONCLUSIONS: The measurement of rabbit IgG levels in patients
      receiving ATG as prophylaxis against GVHD after HSCT may be of value in lowering
      the risk of severe GVHD.

PMID- 15996932
TI  - Prognostic factors identifiable at the time of onset of acute graft-versus-host
      disease after allogeneic hematopoietic cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: Current grading systems of acute graft-versus-host
      disease (GVHD) cannot effectively identify patients with poor prognosis at the
      onset of acute GVHD after allogeneic hematopoietic cell transplantation. DESIGN
      AND METHODS: In a retrospective analysis, we evaluated the prognostic value of
      various clinical parameters at the initiation of treatment in 83 patients who
      developed systemic treatment-requiring acute GVHD after allogeneic hematopoietic
      cell transplantation. RESULTS: Forty-three of 83 patients (52%) experienced
      initial treatment failure (40 required secondary treatment due to lack of
      response and 3 died) and 43 (52%) experienced treatment success, defined as
      completion of treatment (initial and, if given, secondary) within 100 days. The
      GVHD-specific survival rate was 65.5%, with 27 deaths due to GVHD-related
      complications without relapse of underlying malignancies within 1 year. HLA
      mismatched transplantation, visceral initiation, and peripheral blood
      lymphocytopenia ( pound100/mL) were independent variables predicting higher
      initial treatment failure (Odd ratios (OR)=12.225, 12.036, and 7.481,
      respectively). The above variables and initial acute GVHD grade III-IV vs. II
      were independent variables predicting shorter GVHD-specific survival (OR=0.322,
      0.247, 0.340, and 0.385, respectively). High-risk disease status, visceral
      initiation, and hypoalbuminemia ( pound2.8 g/dL) were independent variables
      predicting lower treatment success (OR=0.221, 0.162, and 0.270, respectively).
      The predictive value of visceral initiation and lymphocytopenia for GVHD-specific
      survival was verified in an independent cohort of 58 patients. INTERPRETATION AND
      CONCLUSIONS: Lymphocytopenia and hypoalbuminemia may be useful baseline
      prognostic factors for acute GVHD after allogeneic hematopoietic cell
      transplantation.

PMID- 15996933
TI  - Targeting mutated protein tyrosine kinases and their signaling pathways in
      hematologic malignancies.
AB  - Over the last decade, major advances have been made in the elucidation of
      mechanisms involved in leukemogenesis, and this is particularly true with regard
      to deregulated protein tyrosine kinase (PTK) activation. This progress had led to
      the development of small molecules that specifically inhibit the abnormally
      activated kinase. The first example of such targeted therapy is imatinib
      mesylate, an inhibitor of the BCR-ABL fusion gene that is found in more than 90%
      of patients with Philadelphia positive (Ph+) chronic myeloid leukemia (CML) and
      in 20-30% of those with Ph+ acute lymphoblastic leukemia (ALL). The excellent
      clinical results obtained with imatinib in CML have completely changed the
      therapeutic approach to this disease, and imatinib is now the gold standard for
      treatment of newly diagnosed CML. This has instigated a tremendous effort to
      develop targeted PTK therapy based on the presence of over 40 chromosomal
      translocations that lead to deregulation of 12 different PTK associated with
      various hematologic malignancies. That deregulated PTK are also involved in the
      pathogenesis of acute leukemia is underlined by the frequent occurrence of
      mutations leading to constitutive activation of the FLT3. Experimental as well as
      clinical evidence supports a model of acute leukemia based on the co-operation of
      constitutive active PTK with mutations of transcriptional regulators. Here we
      review the general impact of mutated PTK on the pathogenesis of various
      hematologic malignancies. We also discuss the development of new targeted
      therapies and strategies to circumvent the increasing problems related to the
      emergence of drug resistance by targeting downstream signaling mediators that are
      essential for transformation by deregulated PTK.

PMID- 15996934
TI  - Development of leukemia in donor cells after allogeneic stem cell transplantation
      -a survey of the European Group for Blood and Marrow Transplantation (EBMT).
AB  - Leukemia in donor cells (donor cell leukemia; DCL) has been reported as a rare
      but severe complication of allogeneic stem cell transplantation (SCT). However,
      the incidence, potential pathogenetic factors, therapeutic options and outcome of
      patients suffering from DCL and the leukemia risk of their donors are not well
      defined. A questionnaire survey was carried out within European Blood and Marrow
      Transplantation Group (EBMT) centers. Ninety-one EBMT centers participated in
      this survey, covering 10489 allogeneic SCT between 12/1982 and 09/2003. Fourteen
      cases of DCL, most with a myeloid phenotype (7 cases of acute myeloid leukemia, 3
      each of acute lymphocytic leukemia and 1 case of chronic myeloid leukemia) were
      identified. Demonstration of donor cell origin included molecular analysis of
      chimerism in most cases. DCL type and cytogenetic alterations were independent
      from the original disease. The median time between transplantation and diagnosis
      of DCL was 17 months (4-164). No type of conditioning, donor, graft manipulation,
      graft-versus-host disease prophylaxis or subsequent complications were identified
      as risk factors for DCL. Chemotherapy induced remissions in DCL and 2 of 5
      patients remain alive in remission after a second transplant. None of the stem
      cell donors developed hematologic malignancies (median follow-up period of 9
      years; range 6-30 years). DCL is an extremely rare complication of allogeneic SCT
      in which treatment attempts with chemotherapy and a second SCT are justified.
      Donors are not at an increased risk of developing hematologic malignancies.

PMID- 15996935
TI  - High number of circulating CD34+ cells in patients with myelophthisis.
AB  - Six patients with bone marrow micrometastases from solid cancers presented with
      increased numbers of circulating CD34+ cells; the CD34+ cell counts were very
      high in some cases. By contrast, no patient with metastatic cancer without bone
      marrow involvement showed raised numbers of circulating hemopoietic progenitors.

PMID- 15996936
TI  - Association of the G-463A myeloperoxidase polymorphism with infection in sickle
      cell anemia.
AB  - Infections constitute a principal cause of morbidity and mortality in sickle cell
      anemia (SCA). Here we present evidence to suggest that a polymorphism (G-463A
      MPO) in the gene encoding the myeloperoxidase (MPO) enzyme, important for the
      host defense system, may significantly increase susceptibility to infection in
      SCA.

PMID- 15996937
TI  - Outcome of four patients with chronic myeloid leukemia after imatinib mesylate
      discontinuation.
AB  - Imatinib mesylate (IM) therapy is effective in patients with chronic myeloid
      leukemia (CML). However, whether it should be discontinued in patients who
      achieve sustained molecular response is debated. We describe 4 patients with
      undetectable levels of BCR-ABL transcripts in whom IM therapy was discontinued.
      Two patients relapsed after 7 and 10 months and promptly responded after
      restarting therapy; 2 patients are off therapy at the last follow-up visit after
      14 and 15 months and are still in complete molecular remission.

PMID- 15996938
TI  - Establishment of a human myeloid cell line with trisomy 8 derived from overt
      leukemia following myelodysplastic syndrome.
AB  - A human myeloid cell line with trisomy 8 was newly established from overt
      myelogenous leukemia arising in myelodysplastic syndrome. The cells of this cell
      line showed immature myelocyte characteristics. The karyotype retained trisomy 8.
      This cell line could improve understanding of the pathophysiology of myelogenous
      leukemia with trisomy 8.

PMID- 15996939
TI  - The CYP1A1*2a allele is an independent prognostic factor for acute myeloid
      leukemia.
AB  - Polymorphisms in carcinogen- and drug-metabolizing enzymes may increase the risk
      of acute myeloid leukemia (AML) and may influence prognosis. We report that the
      polymorphic variant of the cytochrome P450 CYP1A1*2A, present in 11.3% of
      patients, is an independent unfavorable prognostic factor for failure-free and
      overall survival in patients with AML.

PMID- 15996940
TI  - Multiplex reverse transcription polymerase chain reaction screening in acute
      myeloid leukemia detects cytogenetically unrevealed abnormalities of prognostic
      significance.
AB  - A commercial multiplex reverse transcription polymerase chain reaction screening
      assay, covering 28 leukemic fusion transcripts, was applied in 143 samples
      obtained from patients with acute myeloid leukemia at primary diagnosis. In five
      patients, a cytogenetically unrevealed fusion gene of prognostic importance was
      detected, while the assay failed to detect one case of t(15;17).

PMID- 15996941
TI  - Valproic acid and all-trans retinoic acid for the treatment of elderly patients
      with acute myeloid leukemia.
AB  - Valproic acid (VPA) has been demonstrated to be able to inhibit histone
      deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in
      inducing the differentiation of acute myeloid leukemia (AML) cells. A pilot study
      of the VPA/ATRA combination was performed in 11 elderly patients with de novo AML
      (median age, 82 years). Complete marrow response was observed in 3 patients,
      including 1 complete remission. Two additional patients had hematologic
      improvement.

PMID- 15996942
TI  - An enzyme-linked immunosorbent assay to screen for inhibitors of the oncogenic
      anaplastic lymphoma kinase.
AB  - The discovery of novel anti-cancer drugs targeting anaplastic lymphoma kinase
      (ALK), an oncogenic tyrosine kinase, raises the need for in vitro assays suitable
      for screening compounds for ALK inhibition. To this aim we have developed and
      optimized an ALK-specific enzyme-linked immunosorbent assay that employs a novel
      ALK peptide substrate and purified ALK kinase domain.

PMID- 15996943
TI  - Highly active antiretroviral therapy and outcome of AIDS-related Burkitt's
      lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study.
AB  - Short, intensive cycles of chemotherapy have resulted in improved survival in
      BurkittOs lymphoma/leukemia (BL) in adults. The prognosis of patients with
      immunodeficiency virus (HIV)-associated BL is considered to be poor, but these
      patients have seldom been treated with BL-specific protocols. However, a study
      (PETHEMA-LAL3/97) in which patients with BL were treated regardless of their HIV
      status failed to find differences between HIV-infected and immunocompetent
      individuals. Furthermore, patients who received highly active antiretroviral
      therapy (HAART) seemed to have a slightly better disease-free survival than those
      who did not (p=0.051). We extended the follow-up analysis to elucidate the role
      of HAART in the survival of HIV-infected patients included in the PETHEMA-LAL3/97
      protocol.

PMID- 15996944
TI  - Detection of tumor-derived antigen receptor DNA by polymerase chain reaction in
      the serum of patients with B-cell chronic lymphocytic leukemia.
AB  - Tumor-derived DNA is detectable in the serum of patients. In this study, tumor
      derived and mononuculear cell DNA from 50 patients with B-cell chronic
      lymphocytic leukemia (B-CLL) was amplified by polymerase chain reaction (PCR) and
      analyzed using polyacrylamide electrophoressis and Genescan analysis. DNA was
      demonstrated in 86% of serum samples. Genescan analysis has significantly
      enhanced the sensitivity and specificity of detection of tumor-derived DNA.

PMID- 15996945
TI  - The effect of subsequent therapies in patients with chronic lymphocytic leukemia
      previously treated with prednisone and either cladribine or chlorambucil.
AB  - We present the long-term follow-up and results of subsequent treatments in
      patients with chronic lymphocytic leukemia treated initially with cladribine +
      prednisone or chlorambucil + prednisone in a randomized, cross-over study. We
      found higher complete and overall responses rates in patients who received
      cladribine + prednisone as first and second-line treatment but no significant
      differences in survival.

PMID- 15996946
TI  - Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or
      refractory multiple myeloma in community practice.
AB  - The clinical data on the efficacy and toxicity of bortezomib as treatment for
      multiple myeloma patients are restricted to prospective phase II studies in
      expert myeloma centers. Here we report a multi-institutional analysis of the
      efficacy and toxicity of bortezomib in patients with relapsed or refractory
      multiple myeloma who were treated in community centers in a compassionate need
      program.

PMID- 15996947
TI  - Exon skipping partially restores factor VIII coagulant activity in patients with
      mild hemophilia A with exon 13 duplication.
AB  - Ectopic mRNA was analyzed by reverse transcriptase polymerase chain reaction (RT
      PCR) in patients with duplication of F8 gene exon 13, a mutation which has been
      demonstrated to be a cause of mild hemophilia A in 32% of Northern Italian
      subjects. Two different transcripts originate from mutated genomic DNA, due to
      alternative splice processes. The larger-sized transcript contains both
      duplicated exons 13, the smaller one contains only one exon 13. The residual
      FVIII:C activity which accounts for the mild hemophilia A phenotype derives from
      the latter transcript.

PMID- 15996948
TI  - Factor XI deficiency with a novel homozygous mutation Trp599Arg near the C
      terminal region.
AB  - We identified a novel mutation in an asymptomatic 72-year old Japanese woman with
      severe factor XI (FXI) deficiency. Sequence analysis showed a homozygous missense
      mutation Trp599Arg (g.234T-->C according to Genbank accession number M20218).
      This residue belongs to a region conserved in human FXI and the FXI of several
      animals. Molecular modeling showed that the Trp599 residue is positioned in an
      alpha helix in the C-terminal region of the FXI molecule.

PMID- 15996949
TI  - Feasibility of early tapering of cyclosporine following reduced-intensity stem
      cell transplantation for advanced hematologic or solid malignancies.
AB  - Although some researchers have reported that early tapering of cyclosporine is
      feasible and beneficial to augment graft-versus-leukemia effects after
      conventional stem-cell transplantation, there is little information on the
      feasibility of this strategy following reduced-intensity stem cell
      transplantation (RIST). We summarized outcomes of 17 patients who underwent early
      tapering of cyclosporine following RIST from HLA-identical siblings.

PMID- 15996950
TI  - New insights into the pathophysiology of gastrointestinal graft-versus-host
      disease using capsule endoscopy.
AB  - We investigated gastrointestinal graft-versus-host-disease using capsule
      endoscopy in patients with abdominal pain and/or diarrhea. We found severe
      pathology involving most of the gut including loss of villi, ulcerations,
      narrowing, bleeding and fistula formation. In 2 patients, capsule endoscopy alone
      established the diagnosis of graft-versus-host-disease. Some ulcerations were
      associated with cytomegalovirus infection.

PMID- 15996951
TI  - Cefpirome as empirical treatment for febrile neutropenia in patients with
      hematologic malignancies.
AB  - Cefpirome, a fourth generation cephalosporin, was administered during 154
      episodes of febrile neutropenia in 106 patients. We assessed the clinical
      efficacy of cefpirome and its activity against isolated pathogens in neutropenic
      patients with hematologic malignancies. In addition, the pharmacokinetics and
      optimal dosing regimen of cefpirome during neutropenia were investigated.

PMID- 15996952
TI  - Modeling the dynamics of pressure propagation and diameter variation in tree
      sapwood.
AB  - A non-steady-state model of water tension propagation in tree stems was
      developed. The model is based on the cohesion theory and the assumption that
      fluctuating water tension driven by transpiration together with the elasticity of
      wood cause variations in the diameter of a tree stem. The change in xylem
      diameter can be linked to water tension in accordance with Hooke's law. The model
      was tested against field measurements of the diurnal change in xylem diameter at
      different heights in a 180-year-old Scots pine tree at Hyytiala, southern
      Finland. Model predictions agreed well with measurements. The effect of tree
      dimensions on pressure propagation was examined with the model. The model
      outcomes were also consistent with results of several field measurements
      presented in the literature.

PMID- 15996953
TI  - Shoot water status and ABA responses of transgenic hybrid larch Larix kaempferi x
      L. decidua to ectomycorrhizal fungi and osmotic stress.
AB  - It has been postulated that osmotic effects on plant tissue are mediated by
      abscisic acid (ABA). Hybrid larch (Larix kaempferi (Lambert) Carr. x L. decidua
      Mill.) plantlets, transformed with the ABA-inducible wheat Em promoter associated
      with the Gus reporter gene, were axenically inoculated with two ectomycorrhizal
      fungi: Cenococcum geophilum Fr., considered tolerant to water stress, and
      Laccaria bicolor (Marie) Orton, considered less tolerant to drought. The
      mycorrhizal and non-mycorrhizal transgenic plantlets were subjected to osmotic
      stress by adding polyethylene glycol (PEG) to the culture medium. In the presence
      of PEG, L. bicolor and C. geophilum reduced shoot water potential and turgor
      potential, but increased host osmotic potential. Treatment of plantlets with PEG
      induced a significant increase in endogenous ABA concentrations. Laccaria bicolor
      and C. geophilum behaved similarly and significantly decreased the ABA response
      of plantlets to PEG treatment. Moreover, inoculation with either fungus regulated
      the ABA response of the plantlets even when the fungus was separated from the
      host by a cellophane sheet that prevented mycorrhiza formation. Although the
      wheat Em promoter was inducible in larch plantlets, it was not regulated by
      endogenous ABA. Induction of the wheat Em promoter in larch plantlets depended on
      organ type, with maximum induction in the root apex. Induction of the Em promoter
      was significantly decreased by mycorrhizal inoculation.

PMID- 15996954
TI  - Drought effects on hydraulic conductivity and xylem vulnerability to embolism in
      diverse species and provenances of Mediterranean cedars.
AB  - We studied hydraulic traits of young plants of the Mediterranean cedar species
      Cedrus atlantica (Endl.) G. Manetti ex Carriere (Luberon, France), C. brevifolia
      (Hook. f.) Henry (Cyprus), C. libani A. Rich (Hadeth El Jebbe, Lebanon) and C.
      libani (Armut Alani, Turkey). With an optimum water supply, no major differences
      were observed among species or provenances in either stem hydraulic conductivity
      (Ks) or leaf specific conductivity (Kl) measured on the main shoot. A moderate
      soil drought applied for 10 weeks induced marked acclimation through a reduction
      in Ks, particularly in the Lebanese provenance of C. libani, and a decrease in
      tracheid lumen size in all species. Cedrus atlantica, which had the smallest
      tracheids, was the species most vulnerable to embolism: a 50% loss in hydraulic
      conductivity (PsiPLC50) occurred at a water potential of -4.4 MPa in the well
      watered treatment, and at -6.0 MPa in the moderate drought treatment. In the
      other species, PsiPLC50 was unaffected by moderate soil drought, and only
      declined sharply at water potentials between -6.4 and -7.5 MPa in both irrigation
      treatments. During severe drought, Ks of twigs and stomatal conductance (g(s))
      were measured simultaneously as leaf water potential declined. For all species,
      lower vulnerability to embolism based on loss of Ks was recorded on current-year
      twigs. The threshold for stomatal closure (10% of maximum g(s)) was reached at a
      predawn water potential (Psi(pd)) of -2.5 MPa in C. atlantica (Luberon) and at 
      3.1 MPa in C. libani (Lebanon), whereas the other provenance and species had
      intermediate Psi(pd) values. Cedrus brevifolia, with a Psi(pd) (-3.0 MPa) close
      to that of C. libani (Lebanon), had the highest stomatal conductance of the study
      species. The importance of a margin of safety between water potential causing
      stomatal closure and that causing xylem embolism induction is discussed.

PMID- 15996955
TI  - Growth strain in the trunk and branches of Chamaecyparis formosensis and its
      influence on tree form.
AB  - Distributions of growth strains in branches, straight trunks and basal sweeping
      trunks of Chamaecyparis formosensis Matsum. trees were measured with strain
      gauges. Microfibril angles (MFAs) of the S2 layer of the cell wall were measured
      by the iodine deposition method and their relationships with growth strain
      examined. The magnitude of the compressive stress on the lower side of trunks
      with a basal sweep was greater than that of the tensile stress at the surface of
      straight trunks. However, transverse compressive stress was similar around the
      trunk regardless of whether normal wood or compression wood was present. The
      released surface growth strains varied with MFA. At MFAs of 20-25 degrees ,
      growth stress changed from tension to compression, and compressive stress
      increased dramatically in the compression wood region. Branches suffer bending
      stress due to self-loading. This stress is superimposed on the growth stress.
      Growth strains on the upper or lower sides of branches were larger than those in
      the trunks, suggesting that generation of growth stress on the lower sides of
      branches with extensive compression wood is affected by the gravitational bending
      stress due to self-loading. We conclude that branch form is affected by the
      interaction between the bending moment due to self-loading and that due to the
      asymmetric distribution of growth stress. Growth strain distribution in a branch
      differed depending on whether the branch was horizontal, upward bending or
      downward bending.

PMID- 15996956
TI  - Leaf photosynthetic traits of 14 tropical rain forest species in relation to leaf
      nitrogen concentration and shade tolerance.
AB  - Variability of leaf traits related to photosynthesis was assessed in seedlings
      from 14 tree species growing in the tropical rain forest of French Guiana. Leaf
      photosynthetic capacity (maximum rate of carboxylation and maximum rate of
      electron transport) was estimated by fitting a biochemical model of
      photosynthesis to response curves of net CO2 assimilation rate versus
      intercellular CO2 mole fraction. Leaf morphology described by leaf mass per unit
      leaf area (LMA), density and thickness, as well as area- and mass-based nitrogen
      (N) and carbon (C) concentrations, were recorded on the same leaves. Large
      interspecific variability was detected in photosynthetic capacity as well as in
      leaf structure and leaf N and C concentrations. No correlation was found between
      leaf thickness and density. The correlations between area- and mass-based leaf N
      concentration and photosynthetic capacity were poor. Conversely, the species
      differed greatly in relative N allocation to carboxylation and bioenergetics.
      Principal component analysis (PCA) revealed that, of the recorded traits, only
      the computed fraction of total leaf N invested in photosynthesis was tightly
      correlated to photosynthetic capacity. We also used PCA to test to what extent
      species with similar shade tolerances displayed converging leaf traits related to
      photosynthesis. No clear-cut ranking could be detected among the shade-tolerant
      groups, as confirmed by a one-way ANOVA. We conclude that the large interspecific
      diversity in photosynthetic capacity was mostly explained by differences in the
      relative allocation of N to photosynthesis and not by leaf N concentration, and
      that leaf traits related to photosynthetic capacity did not discriminate shade
      tolerance ranking of these tropical tree species.

PMID- 15996957
TI  - Regeneration patterns in boreal Scots pine glades linked to cold-induced
      photoinhibition.
AB  - Regeneration patterns of Pinus sylvestris L. juveniles in central Siberian glades
      were studied in relation to cold-induced photoinhibition. Spatial distribution of
      seedlings in different height classes revealed higher seedling densities beneath
      the canopy than beyond the canopy, and significantly higher densities of
      seedlings < 50 cm tall on the north side of the trees. These patterns coincided
      with differences in light conditions. Compared with plants on the north side of
      canopy trees (north-exposed), photosynthetic photon flux (PPF) received by plants
      on the south side of canopy trees (south-exposed) was always higher, making south
      exposed plants more susceptible to photoinhibition, especially on cool mornings.
      Chlorophyll fluorescence data revealed lower photochemical efficiency and
      increased non-photochemical quenching of small (20-50 cm in height), south
      exposed seedlings from spring to early autumn, indicating increased excitation
      pressure on photosynthesis. Maximum rate of oxygen evolution was less in south
      exposed plants than in north-exposed plants. Increased pools of xanthophyll cycle
      pigments and formation of the photoprotective zeaxanthin provided further
      evidence for the higher susceptibility to photoinhibition of south-exposed
      seedlings. A linear mixed model analysis explained many of the physiological
      differences observed in seedlings according to height class and aspect with early
      morning temperature and PPF as predictors. The link between photoinhibition and
      differential distribution of seedlings by height class suggests that
      photoinhibition, together with other environmental stresses, decreases the
      survival of small, south-exposed P. sylvestris seedlings, thereby significantly
      affecting the regeneration pattern of central Siberian pine glades.

PMID- 15996958
TI  - Susceptibility to low-temperature photoinhibition in three conifers differing in
      successional status.
AB  - Susceptibility to photoinhibition of the evergreen conifers Abies alba Mill.,
      Picea abies (L.) Karst. and Pinus mugo Turra was investigated in an unheated
      greenhouse during winter and spring 2003. Photosynthetic performance of the
      seedlings was assessed by chlorophyll a fluorescence and analyses of chlorophyll
      and total carotenoid concentrations in needles. During winter months, maximum
      quantum yield of PSII photochemistry (ratio of variable to maximum fluorescence,
      Fv/Fm) was significantly greater in A. alba than in P. abies and P. mugo. Abies
      alba also sustained higher maximum apparent electron transport rate (ETRmax) than
      P. abies and P. mugo. Total concentrations of chlorophyll and carotenoids in
      needles decreased during the winter in P. mugo and P. abies, but remained stable
      in A. alba. For all species, Fv/Fm decreased from December until February and
      then increased to a maximum in April. Photoinhibition was greatest (Fv/Fm < 0.80)
      in all seedlings in February, the month with the lowest mean temperature.
      Saturating photosynthetic photon flux (PPFsat) and ETRmax were positively related
      to air temperature. All species had lower values of ETRmax and PPFsat in winter
      than in spring. Non-photochemical quenching of chlorophyll fluorescence (NPQ) was
      highest at low air temperatures. Differences among species in susceptibility to
      winter photoinhibition resulted from their specific light preferences and led to
      different mechanisms to cope with photoinhibitory stress. The more shade-tolerant
      A. alba sustained a higher photosynthetic capacity in winter than P. abies and P.
      mugo. Winter photoinhibition in P. abies, P. mugo and, to a lesser extent, in A.
      alba may reflect adaptive photoprotection of the photosynthetic apparatus in
      winter.

PMID- 15996959
TI  - Expression of senescence-associated genes in the leaves of silver birch (Betula
      pendula).
AB  - Development was monitored throughout the entire life span of silver birch (Betula
      pendula Roth.) leaves. The focus was on senescence-related changes in
      photosynthesis and gene expression. The youngest fully developed leaves were
      compared with older senescing leaves in two silver birch lines: the wild-type
      line R and a late-senescing line R3.1. Line R3.1 was found among transgenic lines
      produced with a plasmid containing sense-RbcS and nptII under the control of the
      35S CaMV promoter. Compared with the wild type, line R3.1 showed no general
      change in the mRNA levels of RbcS or Rubisco protein; therefore, it can be
      considered a line whose phenotype is due to insertional mutagenesis. Leaf
      senescence started earlier in line R than in line R3.1. Senescence was
      characterized by declining photosynthesis as indicated by decreases in
      chlorophyll fluorescence, the amount and activity of Rubisco, and the level of
      the ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (RbcS1) mRNA.
      Some well-known senescence-associated genes (SAGs) encoding cysteine proteinases
      (Cyp1, Cyp2) and a pathogenesis-related gene (Pr1) were associated with leaf
      senescence. The expression pattern of Cyp1 indicated that it could serve as a
      molecular marker of leaf senescence in silver birch. Several genes related to
      energy metabolism, antioxidants and phenylpropanoid biosynthesis showed enhanced
      expression during leaf senescence. A distinct pattern in transcript abundance
      during leaf development was revealed for some of the identified SAGs.

PMID- 15996961
TI  - Autumn frost hardiness in Norway spruce plus tree progeny and trees of the local
      and transferred provenances in central Sweden.
AB  - Reforestation with provenances from locations remote from the planting site
      (transferred provenances) or the progeny of trees of local provenances selected
      for superior form and vigor (plus trees) offer alternative means to increase
      yield over that obtained by the use of seed from unselected trees of the local
      provenance. Under Swedish conditions, Norway spruce (Picea abies (L.) Karst.) of
      certain transferred provenances generally has an advantage in productivity
      relative to the local provenance comparable to that of progeny of plus trees. The
      aim of this study was to explore the extent to which productivity gains achieved
      by provenance transfer or the use of plus tree progeny are associated with
      reductions in autumn frost hardiness, relative to that of trees of the local
      provenance. In a field trial with 19-year-old trees in central Sweden, bud
      hardiness was tested on four occasions during the autumn of 2002. Trees of the
      local provenance were compared with trees of a south Swedish provenance
      originating 3 degrees of latitude to the south, a Belarusian provenance and the
      progeny of plus trees of local origin. The Belarusian provenance was the least
      hardy and the local provenance the most hardy, with plus tree progeny and the
      south Swedish provenance being intermediate in hardiness. Both the Belarusian
      provenance and the plus tree progeny were significantly taller than trees of the
      other populations. Within provenances, tree height was negatively correlated with
      autumn frost hardiness. Among the plus tree progeny, however, no such correlation
      between tree height and autumn frost hardiness was found. It is concluded that
      although the gain in productivity achieved by provenance transfer from Belarus
      was comparable to that achieved by using the progeny of plus trees of the local
      provenance, the use of trees of the Belarus provenance involved an increased risk
      of autumn frost damage because of later hardening.

PMID- 15996960
TI  - Effects of two iron sources on iron and cadmium allocation in poplar (Populus
      alba) plants exposed to cadmium.
AB  - Effects of 10 microM cadmium (supplied as Cd nitrate) on the utilization and
      allocation of iron (Fe) were investigated in poplar (Populus alba L.) plants
      grown in nutrient solution with Fe(III)-EDTA or Fe(III)-citrate as the Fe source.
      The effects of Cd were also compared with those of Fe deprivation. The
      accumulation of Fe in roots was 10-fold higher in plants grown with Fe-citrate
      than with Fe-EDTA. Cadmium decreased leaf chlorophyll concentrations and
      photosynthetic rates, and these decreases were more marked in plants grown with
      Fe-citrate than with Fe-EDTA. In both Fe treatments, addition of Cd caused large
      increases in root and shoot apoplasmic and non-apoplasmic Cd contents and
      increases in root Fe content; however, Cd decreased shoot Fe content, especially
      in plants grown with Fe-citrate. New leaves of plants grown with Fe-citrate had
      small cellular (non-apoplasmic) Fe pools, whereas these pools were large in new
      leaves of plants grown with Fe-EDTA. Non-apoplasmic Cd pools in new leaves were
      smaller in plants grown with Fe-citrate than with Fe-EDTA, indicating that
      inactivation of non-apoplasmic Cd pools is facilitated more by Fe-EDTA than by Fe
      citrate. In the presence of Cd, Fe-EDTA was also superior to Fe-citrate in
      maintaining an adequate Fe supply to poplar shoots. Differences in plant
      responses to Fe-EDTA and Fe-citrate may reflect differences in long-distance
      transport of Fe rather than in acquisition of Fe by roots.

PMID- 15996962
TI  - Separating rhizosphere respiration from total soil respiration in two larch
      plantations in northeastern China.
AB  - The potential capacity of soil to sequester carbon in response to global warming
      is strongly regulated by the ratio of rhizosphere respiration to respiration by
      soil microbial decomposers, because of their different temperature sensitivities.
      To quantify relative contributions of rhizosphere respiration to total soil
      respiration as influenced by forest stand development, we conducted a trenching
      study in two larch (Larix gmelini (Rupr.) Rupr.) plantations, aged 17 and 31
      years, in northeastern China. Four plots in each plantation were randomly
      selected and trenched in early May 2001. Soil surface CO2 effluxes both inside
      and outside the plots were measured from May 2001 to August 2002. Soil
      respiration (i.e., the CO2 effluxes outside the trenched plots) varied similarly
      in the two plantations from 0.8 micromol m(-2) s(-1) in winter to 6.0 micromol m(
      2) s(-1) in summer. Rhizosphere respiration (i.e., CO2 efflux outside the
      trenched plots minus that inside the plots) varied from 0.2 to 2.0 micromol m(-2)
      s(-1) in the old forest and from 0.3 to 4.0 micromol m(-2) s(-1) in the young
      forest over the seasons. Rhizosphere respiration, on average, accounted for 25%
      of soil respiration in the old forest and 65% in the young forest. Rhizosphere
      and soil respiration were significantly correlated with soil temperature but not
      with soil water content. We conclude that the role forests play in regulating
      climate change may depend on their age.

PMID- 15996963
TI  - Determinants of biomass production in hybrid willows and prediction of field
      performance from pot studies.
AB  - Pot experiments are often performed to assess plant physiological traits and
      relationships among growth traits under controlled environments. However, the
      reliability of pot studies for predicting the growth and performance of trees in
      the field has rarely been rigorously assessed. We evaluated the suitability of
      pot experiments for predicting field performance, measured as shoot biomass
      production, by investigating determinants of growth in hybrid willows (Salix
      spp.) grown under various environmental conditions in the field, and by comparing
      the data with the results from a corresponding pot study. Biomass production in
      six hybrid willow clones, bred for use as bio-fuels, was assessed in three field
      trials located in central and southeastern Sweden throughout the first 3-year
      cutting cycle. The determinants of biomass productivity, measured as biomass
      allocation and nitrogen (N) economy, were identified in one of the field trials.
      Key traits for shoot biomass production in the field were total leaf area and
      total amount of N; plant N losses by shed leaves were only partly controlled by
      leaf-litter N concentration. These key traits were also obtained from the pot
      study and related to shoot biomass production and abscission-leaf N loss in the
      field. Total leaf area and total N pool of plants grown in pot experiments were
      good predictors of long-term biomass production in the field, whereas shoot
      biomass production, specific leaf area and tissue N concentration of pot-grown
      plants were less suitable as predictors of field performance. Relationships
      between the key traits and shoot biomass production were clone-specific,
      indicating the need for analysis of growth traits at the clone level if field
      performance of trees is to be evaluated based on data from pot studies. Nutrient
      loss components are important for tree performance in the long term and
      evaluations of nutrient loss characteristics at the individual-tree level should
      focus on nutrient pools lost rather than on nutrient concentrations in abscised
      plant parts.

PMID- 15996964
TI  - Carbon and biomass partitioning in balsam fir (Abies balsamea).
AB  - Balsam fir (Abies balsamea (L.) Mill) was extensively sampled to investigate the
      effects of forest management practices, site location, within-crown position,
      tree component (i.e., stem, foliage, branches and roots), and tree social classes
      on biomass and carbon (C) partitioning at the individual tree level and across
      ecological regions. The sites were located in three ecologically distinct forest
      regions of west-central New Brunswick, Canada. There were no significant
      differences in %C content of trees across ecological regions or across tree
      social classes. However, at the individual tree level, significant differences
      were evident in biomass and C allocation between different parts of the tree,
      between treatment types (i.e., unmanaged and pre-commercially thinned stands) and
      between within-crown positions, indicating the need for separate estimates of
      biomass and C content of tree components to obtain more precise estimates of
      quantities at the stand level. Calculating stand C content based on constant
      allocation values, as is commonly done, produced errors of up to 15% compared
      with the values calculated in this study. Three allometric equations of biomass
      and C that account for partitioning among different parts of the tree were
      developed and compared: (1) a third-order polynomial, (2) a modified inverse
      polynomial and (3) a modified Weibull equation. Diameter at breast height (DBH)
      was used as the only explanatory variable to describe fresh biomass, dry biomass
      and C content. All regressions derived showed a high correlation with DBH, with
      most r2 values > 0.95. A comparison of the equation results showed that the
      modified Weibull equation gave consistent results with the best overall fit and
      was the simplest of the three equations investigated. The regressions can be used
      to estimate forest biomass and tree C content at the stand level, given specific
      information on DBH.

PMID- 15996965
TI  - Impact on patients of expanded, general practice based, student teaching:
      observational and qualitative study.
AB  - OBJECTIVES: To compare patients' enablement and satisfaction after teaching and
      non-teaching consultations. To explore patients' views about the possible impact
      that increased community based teaching of student doctors in their practice may
      have on the delivery of service and their attitudes towards direct involvement
      with students. DESIGN: Observational study using validated survey instruments
      (patient enablement index--PEI, and consultation satisfaction questionnaire--CSQ)
      administered after teaching consultations and non-teaching consultations. Ten
      focus groups (two from each practice), comprising five with patients
      participating in prearranged teaching sessions and five with patients not
      participating in these. SETTING: Five general practices in west Suffolk and
      southern Norfolk, England, that teach student doctors on the Cambridge graduate
      medical course. PARTICIPANTS: 240 patients attending teaching consultations
      (response rate 82%, 196 patients) and 409 patients attending non-teaching
      consultations (response rate 72%, 294 patients) received survey instruments. Ten
      focus groups with a total of 34 patients participating in prearranged teaching
      sessions and 20 patients not participating in these. MAIN OUTCOME MEASURES:
      Scores on the patient enablement index and consultation satisfaction
      questionnaire, analysed at the level of all patients, allowing for age, sex,
      general practitioner, and practice, and at the level of the individual general
      practitioner teacher. Qualitative analysis of focus group data. RESULTS:
      Patients' enablement or satisfaction was not reduced after teaching consultations
      compared with non-teaching consultations (mean difference in scores on the
      patient enablement index and consultation satisfaction questionnaire with
      adjustment for confounders 2.24% and 1.70%, respectively). This held true for
      analysis by all patients and by general practitioner teacher. Qualitative data
      showed that patients generally supported the teaching of student doctors in their
      practice. However, this support was conditional on receiving sufficient
      information about reasons for doctors' absence, the characteristics of students,
      and the nature of teaching planned. Many patients viewed their general practice
      as different from hospital and expected greater control over students' presence
      during their consultations. CONCLUSIONS: Patients' enablement and satisfaction
      are not impaired by students' participation in consultations. Patients generally
      support the teaching of student doctors in their general practice but expect to
      be provided with sufficient information and to have a choice about participation,
      so they can give informed consent. Recognising this when organising general
      practice based teaching is important.

PMID- 15996967
TI  - Intention to change drinking behaviour in general practice patients with
      problematic drinking and comorbid depression or anxiety.
AB  - AIMS: This paper examines the interaction of intention to change drinking
      behaviour with comorbid depression and anxiety in pro-actively recruited
      individuals with a range of drinking problems. METHODS: Cross-sectional data of
      408 general practice (GP) patients aged 18-64 years, who meet the diagnostic
      criteria of alcohol dependence or abuse according to DSM-IV, criteria of at-risk
      drinking or binge drinking, were drawn from a brief intervention study. Of the
      sample, 89 participants were diagnosed with comorbid anxiety and/or depressive
      disorders. The Transtheoretical Model (TTM) of behaviour change constructs:
      stages and processes of change, self-efficacy, and decisional balance were
      assessed in relation to presence and absence of the respective psychiatric
      disorders. RESULTS: Analysis including all categories of problematic drinking
      revealed comorbid anxiety and/or depression to be significantly related to later
      stages of change. Within subgroups, this was only true for alcohol abuse, not for
      dependence, at-risk or binge drinking. In addition, comorbidity was related to
      higher use of processes of change and more pros and cons of drinking, when
      compared to non-comorbid participants. Comorbid individuals showed higher
      temptation to drink and lower self-efficacy to abstain from drinking. Separate
      analyses of readiness to change drinking between the categories anxiety/no
      comorbidity and depression/no comorbidity both obtained significance, while for
      anxiety disorders, this was more profound. A multinomial logistic regression
      analysis revealed that adverse consequences better predicted readiness to change
      when compared to comorbidity. DISCUSSION: Individuals with problematic drinking
      and comorbid anxiety or depression may be well accessible for pro-active
      intervention to reduce drinking. Strategies should focus on the enhancement of
      coping skills to control temptation and self-efficacy.

PMID- 15996966
TI  - How strong is the evidence for the use of perioperative beta blockers in non
      cardiac surgery? Systematic review and meta-analysis of randomised controlled
      trials.
AB  - OBJECTIVE: To determine the effect of perioperative beta blocker treatment in
      patients having non-cardiac surgery. DESIGN: Systematic review and meta-analysis.
      DATA SOURCES: Seven search strategies, including searching two bibliographic
      databases and hand searching seven medical journals. STUDY SELECTION AND
      OUTCOMES: We included randomised controlled trials that evaluated beta blocker
      treatment in patients having non-cardiac surgery. Perioperative outcomes within
      30 days of surgery included total mortality, cardiovascular mortality, non-fatal
      myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive
      heart failure, hypotension needing treatment, bradycardia needing treatment, and
      bronchospasm. RESULTS: Twenty two trials that randomised a total of 2437 patients
      met the eligibility criteria. Perioperative beta blockers did not show any
      statistically significant beneficial effects on any of the individual outcomes
      and the only nominally statistically significant beneficial relative risk was
      0.44 (95% confidence interval 0.20 to 0.97, 99% confidence interval 0.16 to 1.24)
      for the composite outcome of cardiovascular mortality, non-fatal myocardial
      infarction, and non-fatal cardiac arrest. Methods adapted from formal interim
      monitoring boundaries applied to cumulative meta-analysis showed that the
      evidence failed, by a considerable degree, to meet standards for forgoing
      additional studies. The individual safety outcomes in patients treated with
      perioperative beta blockers showed a relative risk for bradycardia needing
      treatment of 2.27 (95% CI 1.53 to 3.36, 99% CI 1.36 to 3.80) and a nominally
      statistically significant relative risk for hypotension needing treatment of 1.27
      (95% CI 1.04 to 1.56, 99% CI 0.97 to 1.66). CONCLUSION: The evidence that
      perioperative beta blockers reduce major cardiovascular events is encouraging but
      too unreliable to allow definitive conclusions to be drawn.

PMID- 15996968
TI  - Association of the dopamine transporter gene with alcoholism.
AB  - AIMS: It was investigated whether the allele A9 of the dopamine transporter gene
      (DAT1; SLC6A3) is associated with alcoholism, delirium tremens (DT), alcohol
      withdrawal seizures (AWS), or the daily alcohol intake. METHODS: A group of 102
      healthy subjects and 216 alcoholics, including 97 patients with a history of mild
      withdrawal symptoms, 65 with a history of AWS and 83 with a history of DT were
      genotyped and personal data were achieved for statistical evaluation in a case
      control design. RESULTS: The frequency of individuals carrying the allele A9
      [f(A9+)] was significantly higher (P = 0.01) in the group of alcoholics [f(A9+) =
      0.48] compared with healthy controls [f(A9+) = 0.32]. There was no significant
      association of the allele A9 with severe withdrawal symptoms or the daily amount
      of alcohol consumed. CONCLUSIONS: Our results reveal that the allele A9 is
      strongly associated with alcoholism but not with withdrawal symptoms or daily
      alcohol intake.

PMID- 15996969
TI  - Episode-centred analysis of drinking to intoxication in university students.
AB  - AIMS: To demonstrate the use of an internet-based retrospective diary to measure
      intoxication and to describe the epidemiology of intoxication in a university
      community. METHODS: A probability sample of 1564 New Zealand university students
      completed an Internet-based survey (82% response), including a retrospective
      diary in which the volume consumed on each of the preceding seven days and the
      duration of each episode were recorded, along with the respondent's gender,
      weight, and their typical quantity/frequency of consumption, as a measure of
      tolerance. These parameters were used to compute an estimated blood alcohol
      concentration (EBAC) for each episode. RESULTS: Using an EBAC of 0.08 g/100 ml as
      a criterion for intoxication produced lower estimates of incidence than binge
      drinking guidelines (>40 g for women, >60 g for men), or subjective reports.
      EBACs of 0.08 g per cent were exceeded at least weekly by 37% of women and 39% of
      men. Teenage females had higher EBACs than teenage males, despite lower
      consumption. Intoxication was positively associated with lower age, European or
      Maori ethnicity relative to Asian, Pacific, or other ethnicities, and with
      residential halls relative to other living arrangements. Faculty of study was
      inconsistently related to intoxication. DISCUSSION: Frequent drinking to
      intoxication is normative behaviour in this population group. Of particular
      concern are intoxication levels in females aged 16-21 years and in males
      throughout their 20s. The web-based retrospective diary is a useful means of
      measuring intoxication by self-report. Where time permits it can be enhanced by
      specification of drinking locations and beverage-specific questions.

PMID- 15996970
TI  - Can alcohol lead to inhibition or disinhibition? Applying alcohol myopia to
      animal experimentation.
AB  - AIMS: Animal experimentation often demonstrates that alcohol leads to
      disinhibited behaviour, such as increased aggression, increased social behaviour,
      or increased impulsivity. However, human experimentation demonstrates that
      alcohol can have either disinhibiting or inhibiting effects on behaviour,
      depending on salient environmental cues. Our aim was to illustrate how alcohol
      myopia theory could be applied to the literature assessing the effects of alcohol
      on behaviour in animals. METHODS: The effects of alcohol on animal behaviour were
      reviewed in several domains, including aggression, social behaviours, and
      impulsivity. Suggestions for testing alcohol myopia with animal research
      paradigms were provided. RESULTS: Current animal research paradigms are often
      designed in such a way that alcohol myopia cannot be tested. To test alcohol
      myopia, we recommend manipulating the salience of both impelling and inhibiting
      environmental cues. CONCLUSIONS: Disinhibition alone cannot explain alcohol's
      effects on behaviour. We contend that alcohol myopia theory helps to explain some
      contradictory findings in the human and animal literature. We encourage animal
      researchers to develop research paradigms to provide tests of alcohol myopia.

PMID- 15996971
TI  - Prediction of resistance to erythromycin in the genus Rickettsia by mutations in
      L22 ribosomal protein.
AB  - OBJECTIVES: Typhus group (TG) rickettsiae are naturally susceptible to
      erythromycin whereas spotted fever group (SFG) rickettsioses are not. The aim of
      this study was to compare in silico genetic determinants known to be associated
      with resistance to macrolide compounds. METHODS AND RESULTS: Available sequences
      of the 23S RNA gene, and L4 and L22 ribosomal proteins of rickettsial strains
      were aligned and compared using in silico methods. Although there were no
      sequence differences in domain V of the 23S RNA gene and in the conserved region
      of the L4 ribosomal protein gene, we found that TG rickettsiae had a triple amino
      acid difference in the highly conserved region of the L22 ribosomal protein
      compared with the SFG rickettsiae. CONCLUSIONS: We believe that the triple amino
      acid difference in the L22 ribosomal protein found in this study may explain the
      difference in susceptibility to erythromycin among the Rickettsia genus. Genome
      analysis may help to predict possible molecular mechanisms of resistance for
      fastidious and intracellular bacteria and cloning and expression of such proteins
      should be investigated in the future in order to prove our hypothesis.

PMID- 15996972
TI  - Atazanavir trough plasma concentration monitoring in a cohort of HIV-1-positive
      individuals receiving highly active antiretroviral therapy.
AB  - OBJECTIVES: Atazanavir is a recently approved HIV protease inhibitor (PI). As
      with other PIs, careful attention to potential pharmacokinetic drug interactions
      in clinical practice is necessary. The aim of this study was to assess the
      clinical associations with plasma atazanavir concentrations in HIV-positive
      individuals. METHODS: Individuals established on an atazanavir-containing
      regimen, completed an interviewer-administered questionnaire recording atazanavir
      dosing characteristics, concomitant medication use and adherence. After
      completion, plasma atazanavir concentrations were measured. RESULTS: Of 100
      individuals, mean trough plasma atazanavir concentrations (mug/L) were 282 (95%
      CI 95-468, n = 19) and 774 (95% CI 646-902, n = 81) in those on non- and
      ritonavir-boosted atazanavir regimens, respectively. Eighty-five individuals had
      HIV RNA <50 copies/mL. Seven individuals had atazanavir plasma concentrations
      below the assay limit of detection (<50 microg/L), all of whom had undetectable
      plasma HIV RNA. In a multivariate analysis, nevirapine use was associated with
      significantly lower trough atazanavir concentrations (P = 0.011) and
      lopinavir/ritonavir use with higher trough atazanavir concentrations (P = 0.032).
      Dosing characteristics (including food taken), concomitant medications (including
      drugs used for dyspepsia) and HIV RNA were not significantly associated with
      trough atazanavir concentrations. CONCLUSIONS: In this cohort, despite the wide
      inter-individual variability of atazanavir trough concentrations, no significant
      association with dosing characteristics, concomitant medication (with the
      exception of nevirapine and lopinavir/ritonavir) or virological response was
      observed. Further work is needed to assess the optimal dosing regimen when using
      atazanavir with nevirapine.

PMID- 15996973
TI  - A culture-based study of personal and social influences of adolescent smoking.
AB  - BACKGROUND: A range of factors have been found to influence the onset and
      maintenance of smoking among adolescents. The aim was to explore
      interrelationships among adolescent smoking and certain personal influences
      (academic achievement, life satisfaction and future-orientedness) and social
      influences (hostility, social comparison and perceived friends' smoking) using a
      cultural perspective. METHODS: The study surveyed high school students aged 13
      20, a total sample of 2387 adolescents from randomly selected classes in urban
      and metropolitan areas from Szeged (Hungary), Lublin and Warsaw (Poland), Izmir
      (Turkey) and Ames, Iowa (USA). The self-administered questionnaire contained
      items on smoking, sociodemographics, life satisfaction, future-orientedness,
      academic achievement, hostility, social comparison and perceived friends'
      smoking. RESULTS: The frequency of smoking proved to be the highest among
      Hungarian (58.7%) and Polish (57.6%) adolescents, while the occurrence was 22.1%
      among US and 23.6% among Turkish adolescents. Across the countries, high life
      satisfaction, academic achievement, future orientedness and social comparison
      were related to lower rates of smoking. Perceived friends' smoking was a strong
      influence of adolescent smoking in all samples. Only paths from academic
      achievement and perceived peers' smoking differed across the countries.
      CONCLUSION: Findings suggest that interrelationships between adolescents' smoking
      and its social and personal influences are similar across all countries as a part
      of the developmental processes of adolescence. These findings point to the
      importance of both personal and social influences of adolescent smoking, which
      interact in a complex model, regardless culture or smoking rates.

PMID- 15996974
TI  - Smuggled tobacco, deprivation and addiction.
AB  - OBJECTIVE: To identify the links between smuggled tobacco, deprivation and
      addiction across one Health Authority in the North East of England and identify
      the impact on people living in disadvantaged areas. DESIGN: Anonymous postal
      survey. Sample size 11 443. Multivariate analysis including an 'Ideal Types
      analysis' examined the probabilities of purchase of smuggled tobacco and
      associations with population characteristics. SETTING: Sample taken from across
      the Hull & East Riding Health Authority area in the UK. PARTICIPANTS: Randomly
      selected from those aged 16 and over, who were registered with a GP in the Health
      Authority area on the 1 September 2000. RESULTS: The predicted probability of
      having ever bought smuggled tobacco for a male, employed, heavy smoker living in
      a deprived area was 0.67. A female with the same characteristics had a
      probability of 0.49. For the unemployed the probabilities are 0.55 and 0.37
      respectively. For respondents living in non-deprived areas the probability of
      having ever bought smuggled tobacco was much lower. This probability was further
      reduced for respondents who were unemployed. Respondents living in deprived areas
      had a 134% higher probability of being heavily addicted to tobacco. Links between
      addiction and deprivation are confirmed. CONCLUSIONS: This study confirms and
      extends the findings of previous qualitative studies. The results of this
      analysis demonstrate that people who have bought smuggled tobacco are heavy
      smokers with high levels of addiction, living in socially deprived areas, but are
      more likely to be in employment. They are likely to use smuggled tobacco to save
      money and sustain their smoking habit.

PMID- 15996975
TI  - Issues of cause and control in patient accounts of Type 2 diabetes.
AB  - Patients experience considerable difficulties in making and sustaining health
      related lifestyle changes. Many Type 2 diabetes patients struggle to follow
      disease risk-management advice even when they receive extensive information and
      support. Drawing on a qualitative study of patients with Type 2 diabetes, the
      paper uses discourse analysis to examine their accounts about disease causation
      and disease management, and the implications for how they respond to their
      condition and health services advice. As it is a multifactorial disease,
      biomedical discourse around Type 2 diabetes is complex. Patients are encouraged
      to grasp the complicated message that both cause and medical outcomes related to
      their condition are partly, but not wholly, within their control. Discursive
      constructions identified from respondent accounts indicate how these two messages
      are deployed variously by respondents when accounting for disease causation and
      management. While these constructions (identified in respondent accounts as 'Up
      to me' and 'Down to them') are a valuable resource for patients, equally they may
      be deployed in a selective and detrimental way. We conclude that clear messages
      from health professionals about effective disease management may help patients to
      position themselves more effectively in relation to their condition. More
      importantly, they might serve to hinder the availability of inappropriate and
      potentially harmful patient positions where patients either relinquish
      responsibility for disease management or reject all input from health
      professionals.

PMID- 15996976
TI  - Using focus groups to investigate the educational needs of female injecting
      heroin users in Taiwan in relation to HIV/AIDS prevention.
AB  - This study investigated educational needs of female injecting heroin users in
      Taiwan relating to HIV/AIDS prevention via six focus group discussions in a
      prison. All sessions were audio-taped with respondents' consent and the
      discussions transcribed verbatim. The findings indicated that respondents had
      adequate knowledge about HIV/AIDS, but held misconceptions regarding the modes of
      HIV transmission. Many respondents who did not perceive themselves susceptible to
      AIDS rarely used condoms and occasionally shared needles. Stigma surrounding AIDS
      is pervasive among respondents and they considered contracting cancer would be
      preferable to having AIDS; the latter could precipitate suicide. Lastly, many
      respondents had no confidence in assurances of confidentiality regarding HIV
      testing. Issues of misconceptions, high-risk behaviors, stigma surrounding AIDS
      and confidentiality of HIV testing must be addressed in appropriate HIV/AIDS
      education programmes with respect to the needs of female injecting heroin users.

PMID- 15996977
TI  - Female-specific aspects in the pharmacotherapy of chronic cardiovascular
      diseases.
AB  - Differences in pharmacokinetics, pharmacodynamics, and physiology contribute to
      the phenomenon that women and men frequently respond differently to
      cardiovascular drugs. Hormonal influences, in addition, can play an important
      role: for example, the menstrual cycle, menopause, and pregnancy--as a result of
      fluctuations in concentrations of sexual steroids, and of changes in total body
      water--can be associated with gender-specific differences in the plasma levels of
      cardiovascular drugs. Clinical relevance accordingly results, especially for
      substances with a narrow therapeutic margin. This review treats the most
      important pharmacodynamic gender-relevant differences in this context, and
      surveys available evidence on the benefits of therapy of chronic cardiovascular
      diseases in women. On the whole, the study situation for women is appreciably
      less favourable than for men: owing to the fact that women are under-represented
      in most studies, and that few gender-specific analyses have been conducted.

PMID- 15996978
TI  - The spectrum of adult congenital heart disease in Europe: morbidity and mortality
      in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart
      disease.
AB  - AIMS: To describe clinical and demographic characteristics at baseline of a
      European cohort of adults with congenital heart disease (CHD) and to assess
      mortality and morbidity in a 5 year follow-up period. METHODS AND RESULTS: Data
      collected as part of the Euro Heart Survey on adult CHD was analysed. This
      entailed information transcribed from the files of 4110 patients diagnosed with
      one of eight congenital heart conditions ('defects'), who consecutively visited
      the outpatient clinics of one of the participating centres in 1998. The patients
      were included retrospectively and followed until the end of 2003 for a median
      follow-up of 5.1 years. Notwithstanding their overall relatively good functional
      class and low mortality over the follow-up period, a considerable proportion of
      the patients had a history of endocarditis, arrhythmias, or vascular events.
      There were major differences between the eight defects, both in morbidity and
      regarding specific characteristics. Outcomes were worst in cyanotic defects and
      in the Fontan circulation, but a considerable proportion of the other patients
      also suffer from cardiac symptoms. In particular, arrhythmias are common.
      CONCLUSION: The spectrum of adult CHD in Europe emerging from this survey is one
      of a predominantly young population with substantial morbidity but relatively low
      mortality in a 5 year period.

PMID- 15996979
TI  - Heart rate reduction through lifestyle modification.

PMID- 15996980
TI  - Commentary: verbal autopsies--from small-scale studies to mortality surveillance
      systems.

PMID- 15996982
TI  - Alterations of the glutathione redox state improve apical meristem structure and
      somatic embryo quality in white spruce (Picea glauca).
AB  - In white spruce, an improvement of somatic embryo number and quality can be
      achieved through experimental manipulations of the endogenous levels of reduced
      (GSH) and oxidized (GSSG) glutathione. An optimal protocol for embryo production
      included an initial application of GSH in the maturation medium, followed by
      replacement with GSSG during the remaining maturation period. Under these
      conditions, the overall embryo population more than doubled, and the percentage
      of fully developed embryos increased from 22% to almost 70%. These embryos showed
      improved post-embryonic growth and conversion frequency. Structural studies
      revealed remarkable differences between embryo types, especially in storage
      product deposition pattern and organization of the shoot apical meristem (SAM).
      Compared with their control counterparts, glutathione-treated embryos accumulated
      a larger amount of starch during the early stages of development, and more
      protein and lipid bodies during the second half of development. Differences were
      also noted in the organization of SAMs. Shoot meristems of control embryos were
      poorly organized and were characterized by the presence of intercellular spaces,
      which caused separation of the subapical cells. Glutathione-treated embryos had
      well-organized meristems composed of tightly packed cells which lack large
      vacuoles. The improved organization of the shoot apical meristems in treated
      embryos was ascribed to a lower production of ethylene. Differences in meristem
      structure between control and treated embryos were also related to the
      localization pattern of HBK1, a shoot apical meristem 'molecular marker' gene
      with preferential expression to the meristematic cells of the shoot pole.
      Expression of this gene, which was localized to the apical cells in control
      embryos, was extended to the subapical cells of treated embryos. Overall, it
      appears that meristem integrity and embryo quality are under the direct control
      of the glutathione redox state.

PMID- 15996983
TI  - In vivo 13C NMR metabolite profiling: potential for understanding and assessing
      conifer seed quality.
AB  - High-resolution 13C MAS NMR spectroscopy was used to profile a range of primary
      and secondary metabolites in vivo in intact whole seeds of eight different
      conifer species native to North America, including six of the Pinaceae family and
      two of the Cupressaceae family. In vivo 13C NMR provided information on the total
      seed oil content and fatty acid composition of the major storage lipids in a non
      destructive manner. In addition, a number of monoterpenes were identified in the
      13C NMR spectra of conifer seeds containing oleoresin; these compounds showed
      marked variability in individual seeds of Pacific silver fir within the same seed
      lot. In imbibed conifer seeds, the 13C NMR spectra showed the presence of
      considerable amounts of dissolved sucrose presumed to play a protective role in
      the desiccation-tolerance of seeds. The free amino acids arginine and asparagine,
      generated as a result of storage protein mobilization, were detected in vivo
      during seed germination and early seedling growth. The potential for NMR to
      profile metabolites in a non-destructive manner in single conifer seeds and seed
      populations is discussed. It is a powerful tool to evaluate seed quality because
      of its ability to assess reserve accumulation during seed development or at seed
      maturity; it can also be used to monitor reserve mobilization, which is critical
      for seedling emergence.

PMID- 15996984
TI  - Cellular damage induced by cadmium and mercury in Medicago sativa.
AB  - Alfalfa (Medicago sativa) plantlets were exposed to Cd or Hg to study the
      kinetics of diverse stress indexes. In the so-called beaker-size hydroponic
      system, plantlets were grown in 30 microM of Cd or Hg for 7 d. Oxidative stress
      took place and increased over time, a linear response being observed with Cd but
      not with Hg. To improve the sensitivity of the stress assays used, a micro-assay
      system, in which seedlings were exposed for 24 h, was developed. Phytotoxicity of
      metals, quantified as growth inhibition, was observed well before there was any
      change in the non-protein thiol tissue concentration. When measured with
      conventional techniques, oxidative stress indexes did not show significant
      variation. To trace early and small plant responses to Cd and Hg, a microscopic
      analysis with novel fluorescent dyes, which had not yet been exploited to any
      significant extent for use in plants, was conducted. These fluorescent probes,
      which allowed minute cellular responses to 0, 3, 10, and 30 microM of both metals
      to be visualized in the roots of the alfalfa seedlings, were: (i) 2',7'
      dichlorofluorescin diacetate that labels peroxides; (ii) monochlorobimane that
      stains reduced glutathione/homoglutathione (GSH/hGSH); and (iii) propidium iodide
      that marks nuclei of dead cells. Oxidative stress and cell death increased after
      exposure for 6-24 h to Cd and Hg, but labelling of GSH/hGSH decreased acutely.
      This diminution might be the result of direct interaction of GSH/hGSH with both
      Cd and Hg, as inferred from an in vitro conjugation assay. Therefore, both Cd and
      Hg not only compromised severely the cellular redox homeostasis, but also caused
      cell necrosis. In plants treated with 1 mM L-buthionine sulphoximine, a potent
      inhibitor of GSH/hGSH synthesis, only the oxidative stress symptoms appeared,
      indicating that the depletion of the GSH/hGSH pool was not sufficient to promote
      cell death, and that other phytotoxic mechanisms might be involved.

PMID- 15996985
TI  - Molecular changes associated with the setting up of secondary growth in aspen.
AB  - Vascular secondary growth results from the activity of the vascular cambium,
      which produces secondary phloem and secondary xylem. By means of cDNA-amplified
      fragment length polymorphism (cDNA-AFLP) analysis along aspen stems, several
      potential regulatory genes involved in the progressive transition from primary to
      secondary growth were identified. A total of 83 unique transcript-derived
      fragments (TDFs) was found to be differentiated between the top and the bottom of
      the stem. An independent RT-PCR expression analysis validated the cDNA-AFLP
      profiles for 19 of the TDFs. Among these, seven correspond to new genes encoding
      putative regulatory proteins. Emphasis was laid upon two genes encoding,
      respectively, an AP2/ERF-like transcription factor (PtaERF1) and a RING finger
      protein (PtaRHE1); their differential expression was further confirmed by reverse
      northern analysis. In situ RT-PCR revealed that PtaERF1 was expressed in phloem
      tissue and that PtaRHE1 had a pronounced expression in ray initials and their
      derivatives within the cambial zone. These results suggest that these genes have
      a potential role in vascular tissue development and/or functioning.

PMID- 15996986
TI  - Plasticity and acclimation to light reflected in temporal and spatial changes of
      small-scale macroalgal distribution in a stream.
AB  - The small-scale distribution pattern of macroalgae in the river Ilm, in Germany
      was monitored. These patterns were then related to abiotic factors and tested to
      discover whether the distribution of the common macroalgae, Cladophora glomerata
      (L.) Kutz. and Vaucheria sp., was linked to differences in their photosynthetic
      plasticity. Cladophora glomerata revealed higher maximum photosynthetic electron
      transport rates after acclimation to high light (HL) compared with low light (LL)
      acclimated samples. By contrast, Vaucheria sp. did not acclimate to different
      growth light conditions. The photosynthetic performance of both algae also varied
      according to diurnal conditions. High light caused a reversible decrease of the
      dark-adapted quantum yield (F(v)/F(m)) in C. glomerata and a concomitant
      reversible decrease of the light-adapted quantum yield (DeltaF/F'(m)). In
      Vaucheria sp., F(v)/F(m) remained mostly unchanged over the day, whereas
      DeltaF/F'(m) decreased during the morning at low light. Photosynthetic pigments
      confirmed acclimational differences between the species. HL C. glomerata showed
      increased chlorophyll a:chlorophyll b ratios, and higher amounts of xanthophyll
      cycle pigments compared with LL samples, whereas Vaucheria sp. did not reveal
      differences between the light treatments. While preferences for substrate size,
      water velocity, and depth are similar for C. glomerata and Vaucheria sp., the
      physiological responses to light conditions are different. It is concluded that
      light conditions significantly affect the small-scale spatial distribution of
      macroalgae and that fitness is enhanced in species with a higher plasticity in
      photosynthetic acclimation in unstable environments.

PMID- 15996987
TI  - Complementary interactions between oxidative stress and auxins control plant
      growth responses at plant, organ, and cellular level.
AB  - Plant stress responses are a key factor in steering the development of cells,
      tissues, and organs. However, the stress-induced signal transduction cascades
      that control localized growth and cell size/differentiation are not well
      understood. It is reported here that oxidative stress, exerted by paraquat or
      alloxan, induced localized cell proliferation in intact seedlings, in isolated
      root segments, and at the single cell level. Analysis of the stress-induced
      mitotic activity revealed that oxidative stress enhances auxin-dependent growth
      cycle reactivation. Based on the similarities between responses at plant, tissue,
      or single cell level, it is hypothesized that a common mechanism of reactive
      oxygen species enhanced auxin-responsiveness underlies the stress-induced re
      orientation of growth, and that stress-induced effects on the protoplast growth
      cycle are directly relevant in terms of understanding whole plant behaviour.

PMID- 15996991
TI  - The remote, the mouse, and the no. 2 pencil: the household media environment and
      academic achievement among third grade students.
AB  - BACKGROUND: Media can influence aspects of a child's physical, social, and
      cognitive development; however, the associations between a child's household
      media environment, media use, and academic achievement have yet to be determined.
      OBJECTIVE: To examine relationships among a child's household media environment,
      media use, and academic achievement. METHODS: During a single academic year, data
      were collected through classroom surveys and telephone interviews from an
      ethnically diverse sample of third grade students and their parents from 6
      northern California public elementary schools. The majority of our analyses
      derive from spring 2000 data, including academic achievement assessed through the
      mathematics, reading, and language arts sections of the Stanford Achievement
      Test. We fit linear regression models to determine the associations between
      variations in household media and performance on the standardized tests,
      adjusting for demographic and media use variables. RESULTS: The household media
      environment is significantly associated with students' performance on the
      standardized tests. It was found that having a bedroom television set was
      significantly and negatively associated with students' test scores, while home
      computer access and use were positively associated with the scores. Regression
      models significantly predicted up to 24% of the variation in the scores. Absence
      of a bedroom television combined with access to a home computer was consistently
      associated with the highest standardized test scores. CONCLUSION: This study adds
      to the growing literature reporting that having a bedroom television set may be
      detrimental to young elementary school children. It also suggests that having and
      using a home computer may be associated with better academic achievement.

PMID- 15996988
TI  - Tempos of gene locus deletions and duplications and their relationship to
      recombination rate during diploid and polyploid evolution in the Aegilops
      Triticum alliance.
AB  - The origin of tetraploid wheat and the divergence of diploid ancestors of wheat A
      and D genomes were estimated to have occurred 0.36 and 2.7 million years ago,
      respectively. These estimates and the evolutionary history of 3159 gene loci were
      used to estimate the rates with which gene loci have been deleted and duplicated
      during the evolution of wheat diploid ancestors and during the evolution of
      polyploid wheat. During diploid evolution, the deletion rate was 2.1 x 10(-3)
      locus(-1) MY(-1) for single-copy loci and 1.0 x 10(-2) locus(-1) MY(-1) for loci
      in paralogous sets. Loci were duplicated with a rate of 2.9 x 10(-3) locus(-1)
      MY(-1) during diploid evolution. During polyploid evolution, locus deletion and
      locus duplication rates were 1.8 x 10(-2) and 1.8 x 10(-3) locus(-1) MY(-1),
      respectively. Locus deletion and duplication rates correlated positively with the
      distance of the locus from the centromere and the recombination rate during
      diploid evolution. The functions of deleted and duplicated loci were inferred to
      gain insight into the surprisingly high rate of deletions of loci present
      apparently only once in a genome. The significance of these findings for genome
      evolution at the diploid and polyploid level is discussed.

PMID- 15996992
TI  - Association of television viewing during childhood with poor educational
      achievement.
AB  - BACKGROUND: Excessive television viewing in childhood has been associated with
      adverse effects on health and behavior. A common concern is that watching too
      much television may also have a negative impact on education. However, no long
      term studies have measured childhood viewing and educational achievement.
      OBJECTIVE: To explore these associations in a birth cohort followed up to
      adulthood. DESIGN: Prospective birth cohort study. SETTING: Dunedin, New Zealand.
      PARTICIPANTS: Approximately 1000 unselected individuals born between April 1,
      1972, and March 31, 1973. Ninety-six percent of the living cohort participated at
      26 years of age. MAIN OUTCOME MEASURES: Educational achievement by 26 years of
      age. RESULTS: The mean time spent watching television during childhood and
      adolescence was significantly associated with leaving school without
      qualifications and negatively associated with attaining a university degree. Risk
      ratios for each hour of television viewing per weeknight, adjusted for IQ and
      sex, were 1.43 (95% confidence interval [CI], 1.24-1.65) and 0.75 (95% CI, 0.67
      0.85), respectively (both, P<.001). The findings were similar in men and women
      and persisted after further adjustment for socioeconomic status and early
      childhood behavioral problems. Television viewing during childhood (ages 5-11
      years) and adolescence (ages 13 and 15 years) had adverse associations with later
      educational achievement. However, adolescent viewing was a stronger predictor of
      leaving school without qualifications, whereas childhood viewing was a stronger
      predictor of nonattainment of a university degree. CONCLUSIONS: Television
      viewing in childhood and adolescence is associated with poor educational
      achievement by 26 years of age. Excessive television viewing in childhood may
      have long-lasting adverse consequences for educational achievement and subsequent
      socioeconomic status and well-being.

PMID- 15996993
TI  - Children's television viewing and cognitive outcomes: a longitudinal analysis of
      national data.
AB  - OBJECTIVE: To test the independent effects of television viewing in children
      before age 3 years and at ages 3 to 5 years on several measures of cognitive
      outcomes at ages 6 and 7 years. DESIGN: Using data from a nationally
      representative data set, we regressed 4 measures of cognitive development at ages
      6 and 7 years on television viewing before age 3 years and at ages 3 to 5 years,
      controlling for parental cognitive stimulation throughout early childhood,
      maternal education, and IQ. RESULTS: Before age 3 years, the children in this
      study watched an average of 2.2 hours per day; at ages 3 to 5 years, the daily
      average was 3.3 hours. Adjusted for the covariates mentioned earlier, each hour
      of average daily television viewing before age 3 years was associated with
      deleterious effects on the Peabody Individual Achievement Test Reading
      Recognition Scale of 0.31 points (95% confidence interval [CI], -0.61 to -0.01
      points), on the Peabody Individual Achievement Test Reading Comprehension Scale
      of 0.58 points (95% CI, -0.94 to -0.21 points), and on the Memory for Digit Span
      assessment from the Wechsler Intelligence Scales for Children of -0.10 points
      (95% CI, -0.20 to 0 points). For the Reading Recognition Scale score only, a
      beneficial effect of television at ages 3 to 5 years was identified, with each
      hour associated with a 0.51-point improvement in the score (95% CI, 0.17 to 0.85
      points). CONCLUSIONS: There are modest adverse effects of television viewing
      before age 3 years on the subsequent cognitive development of children. These
      results suggest that greater adherence to the American Academy of Pediatrics
      guidelines that children younger than 2 years not watch television is warranted.

PMID- 15996994
TI  - Fast-food intake and diet quality in black and white girls: the National Heart,
      Lung, and Blood Institute Growth and Health Study.
AB  - OBJECTIVE: To examine trends in fast-food consumption and its relationship to
      calorie, fat, and sodium intake in black and white adolescent girls. DESIGN: A
      longitudinal multicenter cohort study of the development of obesity and
      cardiovascular risk factors in black and white female adolescents. Data
      collection occurred annually using a validated 3-day food record and a food
      patterns questionnaire. SUBJECTS AND SETTINGS: A biracial and socioeconomically
      diverse group of 2379 black and white girls recruited from 3 centers. MAIN
      OUTCOME MEASURE: Three-day food records and a food-patterns questionnaire were
      examined for intake of fast food and its association with nutrient intake. We
      compared patterns of exposure to fast food and its impact on intake of calories,
      fat, and sodium. RESULTS: Fast-food intake was positively associated with intake
      of energy and sodium as well as total fat and saturated fat as a percentage of
      calories. Fast-food intake increased with increasing age in both races. With
      increasing consumption of fast food, energy intake increased with an adjusted
      mean of 1837 kcal for the low fast-food frequency group vs 1966 kcal for the
      highest fast-food frequency group (P<.05). Total fat in the low fast-food
      frequency group was 34.3% as opposed to 35.8% in the highest fast-food frequency
      group (P<.05). Saturated fat went from 12.5% to 13% and sodium increased from
      3085 mg to 3236 mg in the lowest vs the highest fast-food frequency group
      (P<.001). CONCLUSIONS: Dietary intake of fast food is a determinant of diet
      quality in adolescent girls. Efforts to reduce fast-food consumption may be
      useful in improving diet and risk for future cardiovascular disease.

PMID- 15996996
TI  - Diagnosis, evaluation, and treatment of childhood obesity in pediatric practice.
AB  - OBJECTIVE: To determine rates of diagnosis and treatment, and types of treatment,
      among overweight children in clinical practice. DESIGN: Six hundred randomly
      selected records were reviewed. SETTING: Two community-based and 2 hospital-based
      clinics in New Haven. PARTICIPANTS: Children aged 3 to 17 years with a health
      maintenance visit from January 1, 1999, to December 31, 2000. Children classified
      according to body mass index (BMI) (calculated as weight in kilograms divided by
      the square of height in meters) lower than the 85th percentile were designated as
      nonoverweight; 85th to 94th percentile, at risk of overweight; and 95th
      percentile or greater, overweight. MAIN OUTCOME MEASURES: We examined the text of
      the encounter note for documentation of BMI, corresponding diagnosis regarding
      overweight, examination for comorbid disease, and treatment for overweight.
      RESULTS: Among 600 patients, 52.6% were male, 34.5% were black, 35.1% were Latin
      American, 57.2% were in single-parent households, and 84.0% received Medicaid.
      Overall, 39.8% were at risk of overweight (n = 107; range across sites, 14.7%
      20.0%) or were overweight (n = 132; range across sites, 18.0%-28.0%). The BMI was
      documented in 0.5% (n = 3) of medical records. Among the 239 children at risk of
      overweight or overweight, 20.5% had a documented diagnosis (range, 12%-37%) and
      16.9% had documented treatment (range, 6%-34%). The most common strategies among
      the 41 subjects with documented treatment (overweight and at risk of overweight
      patients) were diet (74%) and increased activity (49%). Treatment recommendations
      were often limited to general advice (eg, "recommended diet" [n = 19] or
      "increase exercise" [n = 16]). CONCLUSION: Despite a high burden of overweight,
      routine screening with BMI was not documented and few children received a formal
      diagnosis or treatment.

PMID- 15996997
TI  - Televised state-sponsored antitobacco advertising and youth smoking beliefs and
      behavior in the United States, 1999-2000.
AB  - BACKGROUND: Recent state budget crises have dramatically reduced funding for
      state-sponsored antitobacco media campaigns. If campaigns are associated with
      reduced smoking, such cuts could result in long-term increases in state health
      care costs. METHODS: Commercial ratings data on mean audience exposure to
      antitobacco advertising that appeared on network and cable television across the
      largest 75 media markets in the United States for 1999 through 2000 were combined
      with nationally representative survey data from school-based samples of youth in
      the contiguous 48 states. Multivariate regression models were used to analyze
      associations between mean exposure to state antitobacco advertising and youth
      smoking-related beliefs and behaviors, controlling for individual and
      environmental factors usually associated with youth smoking and other televised
      tobacco-related advertising. RESULTS: Mean exposure to at least 1 state-sponsored
      antitobacco advertisement in the past 4 months was associated with lower
      perceived rates of friends' smoking (odds ratio [OR], 0.72; 95% confidence
      interval [CI], 0.58-0.88), greater perceived harm of smoking (OR, 1.25; 95% CI,
      1.11-1.42), stronger intentions not to smoke in the future (OR, 1.43; 95% CI,
      1.17-1.74), and lower odds of being a smoker (OR, 0.74; 95% CI, 0.63-0.88).
      CONCLUSIONS: To our knowledge, this study is the first to explore the potential
      impact of state-sponsored antitobacco media campaigns while controlling for other
      tobacco-related advertising and other tobacco control policies. State-sponsored
      antitobacco advertising is associated with desired outcomes of greater
      antitobacco sentiment and reduced smoking among youth. Recent cuts in these
      campaigns may have future negative health and budgetary consequences.

PMID- 15996998
TI  - Blood lead testing among Medicaid-enrolled children in Michigan.
AB  - BACKGROUND: Federal regulations mandate that Medicaid-enrolled children be tested
      for lead poisoning at the age of 1 and 2 years or 3 through 5 years if not
      previously tested. OBJECTIVES: To measure the rate of blood lead testing among
      Medicaid-enrolled children in Michigan and the subsequent proportion of children
      with elevated lead levels and to determine factors associated with testing and
      elevated lead levels. METHODS: We performed a retrospective analysis of children
      aged 5 years or younger continuously enrolled in Michigan Medicaid during 2002.
      RESULTS: There were 216,578 children included in the analysis. The overall rate
      of blood lead testing was 19.6% (95% confidence interval [CI], 19.4-19.8) of
      which 8.3% (95% CI, 8.0-8.5) had a level of 10 microg/dL [0.48 micromol/L] or
      higher. Hispanic or nonwhite children or those living in high-risk areas for lead
      exposure were more likely to be tested and more likely to have an elevated blood
      lead level. However, 1.2% of tested children without these additional risk
      factors had a level of 10 microg/dL or higher. Enrollment in Medicaid managed
      care was associated with an increased likelihood of blood lead testing. After
      adjusting for other factors, those in managed care for 75% or more of their
      enrollment in 2002 had 1.98 (95% CI, 1.46-2.68) greater odds of being tested than
      those in fee-for-service for 75% or more of their enrollment. CONCLUSIONS: The
      rate of blood lead testing was low. Patterns suggest testing was targeted to
      those at highest risk, potentially leading some children with elevated blood lead
      levels to be missed.

PMID- 15996999
TI  - Neurocognitive functioning in pediatric human immunodeficiency virus infection:
      effects of combined therapy.
AB  - OBJECTIVES: To assess the impact of combination antiretroviral therapy on
      neurocognitive outcomes in perinatally human immunodeficiency virus (HIV)
      infected patients and to determine if CD4 percentage and plasma HIV-1 RNA level
      (viral load) are predictive of future neurocognitive function. DESIGN:
      Retrospective cohort study. SETTING: An HIV-dedicated urban care center.
      PARTICIPANTS: One hundred forty-six perinatally HIV-infected children born
      between June 1990 and May 2003 with at least 1 neurocognitive evaluation. MAIN
      OUTCOME MEASURES: Neurocognitive standard testing scores as well as diagnosis of
      progressive encephalopathy, probable progressive encephalopathy, or static
      encephalopathy. RESULTS: The prevalence of progressive encephalopathy has
      decreased in children born prior to 1996 (period 1) compared with those born
      after 1996 (period 2) from 29.6% to 12.1% (P = .049). The prevalence of all
      progressive encephalopathy and static encephalopathy decreased from 40.7% to
      18.2% in period 1 vs 2 (P = .02). For those diagnosed as neurocognitively
      healthy, neurocognitive scores remained stable over time with a mean (SD)
      standard score of 89.6 (11.8) at first evaluation compared with 91.9 (11.93) at
      most recent evaluation. The most recent mean (SD) standard score increased from
      82.3 (18) to 87.2 (10.49) in period 1 vs period 2 (P = .001). A weak association
      was found between both the mean viral load (P = .06) and CD4 percentage (P<.001)
      and neurocognitive testing score 6 months later. CONCLUSIONS: Since 1996, fewer
      children have been diagnosed with progressive encephalopathy, and neurocognitive
      functioning is preserved over time in those deemed neurocognitively healthy at
      entry. Viral load and CD4 percentage are marginally predictive of future changes
      in neurocognitive standard scores. These data support the observation that
      combination antiretroviral therapy is associated with improved neurocognitive
      outcomes in children with perinatally acquired HIV infection.

PMID- 15997000
TI  - Predicting adolescents' longitudinal risk for sexually transmitted infection:
      results from the National Longitudinal Study of Adolescent Health.
AB  - BACKGROUND: Influencing adolescents' sexual behaviors has the potential to
      influence trajectories of risk for sexually transmitted infections (STIs) among
      young adults. OBJECTIVE: To determine whether family, school, and individual
      factors associated with increased duration of virginity also protect against STIs
      in young adulthood. DESIGN: Prospective cohort study. Wave I of the National
      Longitudinal Study of Adolescent Health occurred in 1995 when participants were
      in grades 7 through 12. Six years later, all wave I participants who could be
      located were invited to participate in wave III and provide a urine specimen for
      STI testing. SETTING: In-home interviews in the continental United States,
      Alaska, and Hawaii. PARTICIPANTS: Population-based sample. Of 18,924 participants
      in the nationally representative weighted wave I sample, 14,322 (75.7%) were
      located and participated in wave III. Test results for Chlamydia trachomatis,
      Neisseria gonorrhoeae, and Trichomonas vaginalis were available for 11,594
      (81.0%) of wave III participants. MAIN OUTCOME MEASURE: Positive test result for
      C. trachomatis, N. gonorrhoeae, or T. vaginalis. RESULTS: Controlling for
      biological sex, age, race/ethnicity, family structure, and maternal education,
      adolescents who perceived that their parents more strongly disapproved of their
      having sex during adolescence were less likely to have STIs 6 years later
      (adjusted odds ratio, 0.89; 95% confidence interval, 0.81-0.99). Those with a
      higher grade point average during adolescence were also less likely to acquire
      STIs (adjusted odds ratio, 0.84; 95% confidence interval, 0.71-0.99). Stratified
      analyses confirmed these findings among female, but not male, adolescents.
      Feelings of connection to family or school, reported importance of religion,
      attending a parochial school, and pledges of virginity during adolescence did not
      predict STI status 6 years later. CONCLUSIONS: Perceived parental disapproval of
      sexual intercourse and higher grades in school during adolescence have protective
      influences on the trajectory of risk for acquiring STIs, primarily among female
      adolescents. Most factors associated with increased duration of virginity in
      adolescence do not influence the trajectory of STI risk.

PMID- 15997001
TI  - Prehospital and in-hospital mortality: a comparison of intentional and
      unintentional traumatic brain injuries in Colorado children.
AB  - OBJECTIVES: To describe the incidence and case-fatality rates of traumatic brain
      injury (TBI) in young children in Colorado, to compare these injuries based on
      intentionality and outcome (prehospital death, in-hospital death, or survival),
      and to model the association of intentionality with TBI-related mortality.
      METHODS: Cases were drawn from the 1994-2002 Colorado Traumatic Brain Injury
      Surveillance System. Incidence and case-fatality rates for intentional and
      unintentional TBI were calculated. We performed univariate comparisons based on
      the intentionality and outcome of the TBI. Multivariate logistic regression was
      used to estimate the association of intentionality and mortality, controlling for
      injury severity. RESULTS: Of the 1333 children aged 0 to 36 months with TBI, 340
      had intentional and 993 had unintentional TBI. Incidence for intentional and
      unintentional TBI was 16.1 and 47.0 per 100,000, respectively. Children with
      intentional TBI had a higher case-fatality rate, in-hospital death rate, and
      injury severity. Intentional TBI deaths were twice as likely to occur in hospital
      than prehospital, whereas unintentional TBI deaths were twice as likely to occur
      prehospital. Intentionality was significantly associated with mortality, with the
      effect increasing with increasing age. CONCLUSION: Intentionality--independent of
      severity--raises the mortality of TBI in young children.

PMID- 15997002
TI  - Diagnostic value of abdominal radiography in constipated children: a systematic
      review.
AB  - BACKGROUND: Constipation is a common problem in children. Diagnosis is based on
      clinical features. In case of doubt about the presence of constipation, the
      existence of fecal retention can be evaluated on plain abdominal radiography.
      OBJECTIVES: To describe and to assess the evidence from observational, controlled
      studies concerning the association between abdominal radiography and symptoms and
      signs related to constipation in children. METHODS: MEDLINE was searched from
      inception to April 2004 using a specified search strategy. Studies that fulfilled
      predefined criteria were assessed for methodological quality. Study
      characteristics and associations were extracted and the results were summarized
      according to a best-evidence synthesis. RESULTS: Of the 392 publications
      identified, 6 studies met the inclusion criteria. Only 2 studies were of high
      methodological quality. The best-evidence synthesis yielded conflicting evidence
      for an association between a clinical and a radiological diagnosis of
      constipation. The likelihood ratio (LR) in 2 high-quality studies was close to 1
      (LR, 1.2; 95% confidence interval [CI], 1.0-1.4; and LR, 1.0; 95% CI, 0.5-1.6).
      Conflicting evidence was found for an association between digital rectal
      examination and fecal impaction on radiography. Limited evidence was found for an
      association between a history of hard stool and a finding of rebound tenderness
      and radiography (LR, 1.2; 95% CI, 1.0-1.4; and LR, 1.1; 95% CI, 1.0-1.2,
      respectively). CONCLUSIONS: The limited amount of data available shows
      conflicting evidence for an association between clinical symptoms of constipation
      and fecal loading on abdominal radiographs in children. The recommendation to
      perform a plain abdominal radiograph in case of doubt of the presence of
      constipation in a child cannot be supported. Further research of good
      methodological quality is needed.

PMID- 15997003
TI  - Delayed prescription may reduce the use of antibiotics for acute otitis media: a
      prospective observational study in primary care.
AB  - OBJECTIVES: To evaluate the applicability and the effectiveness of practice
      guidelines based on a wait-and-see strategy for children with acute otitis media
      (AOM). POPULATION: Children from 1 to 14 years old having AOM who were referred
      to primary care pediatric practices. STUDY DESIGN: Prospective observational
      study. MAIN OUTCOME MEASURE: Proportion of children having a diagnosis of AOM and
      eligible for symptomatic treatment who, at 72 hours from enrollment, recovered
      from their symptoms (fever and earache) without receiving antibiotic treatment.
      RESULTS: One hundred sixty-nine pediatricians participated in the study and
      enrolled 1672 children. One thousand two hundred seventy-seven children were
      included in the analysis. One hundred seventy-eight children received antibiotic
      treatment at first contact according to the practice guidelines criteria
      (presence of otorrhea or recurrent AOM). Of the 1099 children who were eligible
      for symptomatic treatment only, 743 (67.6%) recovered without antibiotic
      treatment at 3 days and 716 (65.1%) at 30 days. No complications were observed.
      Coexistence of a high fever (temperature > or = 38.4 degrees C) and red and
      bulging tympanic membrane as well as male sex were significantly associated with
      antibiotic use. CONCLUSIONS: Practice guidelines based on a wait-and-see strategy
      for children with AOM are applicable and effective in primary care. This strategy
      was able to avoid the administration of antibiotic treatment in 2 of 3 children.

PMID- 15997004
TI  - State tobacco counteradvertising and adolescents.

PMID- 15997006
TI  - The relationship between children's television viewing and academic performance.

PMID- 15997007
TI  - Child neurocognitive and behavioral outcomes and maternal solvent exposure during
      pregnancy.

PMID- 15997008
TI  - Incidence of autism.

PMID- 15997009
TI  - Herb-drug interaction implications in pediatric practice: an overview of
      pharmacokinetic trials.

PMID- 15997010
TI  - Jeanne Hebuterne.

PMID- 15997011
TI  - Does treating post-myocardial infarction depression reduce medical mortality?

PMID- 15997012
TI  - Attitudes toward antipsychotic medication: the impact of clinical variables and
      relationships with health professionals.
AB  - CONTEXT: Nonadherence to antipsychotic medication is a major cause of psychotic
      relapse and is strongly influenced by attitudes toward treatment. Although
      patient variables such as insight and symptoms that contribute toward attitudes
      have been identified, the contributions of relationship and service factors have
      not been adequately studied. OBJECTIVE: To determine relations between clinical
      and service variables and attitudes toward medication in people with a diagnosis
      of schizophrenia and schizoaffective disorder. DESIGN: Consecutively admitted
      patients were approached to take part; 23 refused. Measures included symptoms,
      insight, drug adverse effects, self-reported adherence, attitudes toward
      treatment, perceived relationship with the prescriber, ward atmosphere, and
      admission experience. Data were analyzed by a proportional odds model and
      structural equation modeling to test predicted paths between experience of
      admission, relationship variables, attitudes toward treatment, and self-reported
      adherence to medication. SETTING: Twenty-eight inpatient wards at 8 hospitals in
      North Wales and the Northwest of England. Sites included hospitals with inner
      city and rural catchment areas. Patients Two hundred twenty-eight patients
      meeting DSM-IV criteria for schizophrenia or schizoaffective disorder, assessed
      during acute admission. MAIN OUTCOME MEASURES: Attitudes toward treatment and
      self-reported adherence to medication. RESULTS: The data fit a model in which
      attitudes toward treatment were predicted by insight, relationship with staff
      (especially the physician-prescriber), and the patient's admission experience
      (maximum likelihood chi(2)(49) = 89.3, P<.001). A poor relationship with the
      prescriber, experience of coercion during admission, and low insight predicted a
      negative attitude toward treatment. CONCLUSIONS: The quality of relationships
      with clinicians during acute admission appears to be an important determinant of
      patients' attitudes toward treatment and adherence to medication. Enhancing such
      relationships may yield important clinical benefits.

PMID- 15997013
TI  - Assessment of capacity to consent to research among older persons with
      schizophrenia, Alzheimer disease, or diabetes mellitus: comparison of a 3-item
      questionnaire with a comprehensive standardized capacity instrument.
AB  - CONTEXT: Considerable discussion surrounds issues related to the capacities of
      neuropsychiatric patients to consent to research, yet few empirical
      investigations have directly compared decisional capacity among patients with a
      serious mental illness with that among patients with neurologic or medical
      conditions. Also, as requirements for formal assessment of decisional capacity
      are becoming more common, there is a clear need to identify efficient screening
      methods. OBJECTIVES: To compare decisional capacity among 3 diagnostic groups,
      and to examine the degree to which impaired understanding can be detected with a
      brief set of screening questions. SETTING: Outpatient veterans hospital clinic
      and university-based neuropsychiatric research centers. DESIGN/ PARTICIPANTS:
      Cross-sectional comparison of decisional capacity among older (>/=60 years)
      outpatients with schizophrenia (n = 35), mild to moderate Alzheimer disease (n =
      30), and type 2 diabetes mellitus (n = 36), and determination of sensitivity and
      specificity of a screening measure. MAIN OUTCOME MEASURES: Three-item decisional
      capacity questionnaire and the MacArthur Competence Assessment Tool for Clinical
      Research. RESULTS: Patients with diabetes mellitus performed the best on the
      capacity instruments, patients with Alzheimer disease had the worst performance,
      and patients with schizophrenia were intermediate. However, there was
      considerable heterogeneity within each group. Even within diagnostic groups, the
      level of cognitive functioning (measured with the Mini-Mental State Examination)
      was generally the best predictor of decisional capacity (particularly in the
      understanding component). The 3-item questionnaire was sensitive to impaired
      understanding as measured with the MacArthur Competence Assessment Tool for
      Clinical Research understanding subscale. CONCLUSIONS: Decisional capacity
      differed among the 3 groups; there was considerable heterogeneity even within
      each diagnostic group, so individualized consideration of capacity may be
      warranted. The level of cognitive deficits is 1 potential marker of which
      participants should receive comprehensive capacity evaluations, but sensitive
      brief questionnaires targeting key aspects of disclosed information may also
      provide an effective means of screening for participants warranting comprehensive
      capacity evaluations.

PMID- 15997014
TI  - Frontotemporal alterations in pediatric bipolar disorder: results of a voxel
      based morphometry study.
AB  - CONTEXT: While numerous magnetic resonance imaging (MRI) studies have evaluated
      adults with bipolar disorder (BPD), few have examined MRI changes in children
      with BPD. OBJECTIVE: To determine volume alterations in children with BPD using
      voxel-based morphometry, an automated MRI analysis method with reduced
      susceptibility to various biases. A priori regions of interest included amygdala,
      accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal
      cortex. DESIGN: Ongoing study of the pathophysiology of pediatric BPD. SETTING:
      Intramural National Institute of Mental Health; approved by the institutional
      review board. Patients Pediatric subjects with BPD (n = 20) with at least 1 manic
      or hypomanic episode meeting strict DSM-IV criteria for duration and elevated,
      expansive mood. Controls (n = 20) and their first-degree relatives lacked
      psychiatric disorders. Groups were matched for age and sex and did not differ in
      IQ. MAIN OUTCOME MEASURES: With a 1.5-T MRI machine, we collected 1.2-mm axial
      sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled
      echo in the steady state sequence. Image analysis was by optimized voxel-based
      morphometry. RESULTS: Subjects with BPD had reduced gray matter volume in the
      left DLPFC. With a less conservative statistical threshold, additional gray
      matter reductions were found in the left accumbens and left amygdala. No
      difference was found in the hippocampus or orbitofrontal cortex. CONCLUSIONS: Our
      results are consistent with data implicating the prefrontal cortex in emotion
      regulation, a process that is perturbed in BPD. Reductions in amygdala and
      accumbens volumes are consistent with neuropsychological data on pediatric BPD.
      Further study is required to determine the relationship between these findings in
      children and adults with BPD.

PMID- 15997015
TI  - Alcohol misuse and mood disorders following traumatic brain injury.
AB  - CONTEXT: Alcohol abuse and/or dependence (AA/D) and mood disturbance are co
      occurring conditions among patients who have had a traumatic brain injury (TBI).
      However, the relationship between these disorders has not been extensively
      studied. OBJECTIVE: To examine the relationship of AA/D and post-TBI mood
      disorders and the effect of these conditions on psychosocial outcome. DESIGN:
      Prospective, case-control surveillance study conducted during the first year
      following trauma. Settings University hospital level I trauma centers and
      specialized rehabilitation units. Patients One hundred fifty-eight TBI patients
      with closed head injury with and without a history of AA/D. METHODS: We
      prospectively compared psychiatric, neuropsychological, and psychosocial outcomes
      among the patients, who were evaluated at baseline and at 3, 6, and 12 months
      after trauma. Psychiatric diagnosis was made using a structured clinical
      interview and DSM-IV criteria. Neuropsychological testing results and
      quantitative magnetic resonance images were obtained at the 3-month follow-up.
      RESULTS: A history of AA/D was significantly more frequent among patients who
      developed mood disorders during the first year following TBI. There was also a
      significantly higher frequency of mood disorders among patients with alcohol
      abuse relapse. Patients with a history of AA/D had significantly reduced frontal
      gray matter volumes than did patients without a history of alcohol abuse. In
      addition, patients who resumed alcohol abuse had decreased medial frontal gray
      matter volumes and impaired performance in executive tasks. Both AA/D and mood
      disorders following TBI were associated with a poor vocational outcome.
      CONCLUSIONS: Previous alcohol abuse increases the risk of developing mood
      disorders after TBI, and emotional disturbance, in turn, increases the risk of
      alcohol abuse relapse. Alcohol's neurotoxic effects and TBI likely interact to
      produce greater disruption of the neural circuits that modulate reward, mood, and
      executive function. Patients with a history of AA/D who also developed mood
      disorders following TBI had major difficulties resuming a productive life.

PMID- 15997016
TI  - Long-term stability of alcohol and other substance dependence diagnoses and
      habitual smoking: an evaluation after 5 years.
AB  - CONTEXT: A major criterion to validate diagnoses is stability over time.
      OBJECTIVE: To examine the stability of several classification systems for
      lifetime diagnosis of alcohol dependence, to identify characteristics predicting
      stability of alcoholism, and to study stability of lifetime assessments of
      habitual smoking (1 pack per day for at least 6 months) and other drug
      dependence. DESIGN: Participants in the Collaborative Study on the Genetics of
      Alcoholism were interviewed using the Semi-Structured Assessment for the Genetics
      of Alcoholism and reevaluated 5 years later. Initial and follow-up interviews
      were available for 1728 individuals (641 index cases, 800 siblings, 287 controls)
      with lifetime diagnoses of alcohol dependence, other substance dependence
      (marijuana, cocaine, other stimulants, sedatives, opioids), or habitual smoking
      at first interview. The likelihood that an individual with a lifetime history of
      substance dependence or habitual smoking at the first interview retained this
      classification after 5 years was examined to assess stability of diagnosis.
      RESULTS: Stability of a lifetime diagnosis of alcohol dependence varied among the
      subject groups of index cases, siblings, and community-based controls. Alcohol
      dependence as defined by DSM-III-R criteria was highly stable in the index cases
      (90.5% women, 94.7% men) but much less stable in the community-based controls
      (27.5% women, 64.7% men). The most important characteristic associated with
      stability of diagnosis of alcohol dependence was severity, defined by the number
      of alcohol-related symptoms. Other DSM-III-R substance dependence disorders
      varied in the stability of diagnosis over a 5-year period. Lifetime history of
      habitual smoking was highly stable in all subject groups (96.0% overall).
      CONCLUSIONS: Stability of lifetime assessment of alcohol dependence varies
      depending on severity of illness. Severe cases of alcohol dependence are more
      likely to be stable, whereas general population cases of alcohol dependence are
      less likely to have stable diagnoses. The stability of diagnosis for other
      substance dependence varies from substance to substance.

PMID- 15997017
TI  - Neural activation patterns of methamphetamine-dependent subjects during decision
      making predict relapse.
AB  - CONTEXT: Relapse is a common clinical problem in individuals with substance
      dependence. Previous studies have implicated a multifactorial process underlying
      relapse; however, the contribution of specific neural substrates has not yet been
      examined. OBJECTIVE: To determine whether results from functional magnetic
      resonance imaging (fMRI) shortly after drug cessation could predict relapse in
      stimulant-dependent individuals. PARTICIPANTS AND DESIGN: Treatment-seeking
      methamphetamine-dependent males (N = 46) underwent fMRI 3 to 4 weeks after
      cessation of drug use. Of the 40 subjects who were followed up a median of 370
      days, 18 relapsed and 22 did not. MAIN OUTCOME MEASURE: Blood oxygen level
      dependent fMRI activation during a simple 2-choice prediction task. RESULTS: The
      fMRI activation patterns in right insular, posterior cingulate, and temporal
      cortex obtained early in recovery correctly predicted 20 of 22 subjects who did
      not relapse and 17 of 18 subjects who did. A Cox regression analysis revealed
      that the combination of right middle frontal gyrus, middle temporal gyrus, and
      posterior cingulate activation best predicted the time to relapse. CONCLUSION: To
      our knowledge, this is the first investigation to show that fMRI can be used to
      predict relapse in substance-dependent individuals.

PMID- 15997018
TI  - Personality and problem gambling: a prospective study of a birth cohort of young
      adults.
AB  - CONTEXT: Individual differences in dimensions of personality may play an
      important role in explaining risk for disordered gambling behavior as well as the
      comorbidity between disordered gambling behavior and other substance-related
      addictive disorders. OBJECTIVES: To identify the personality correlates of
      problem gambling in a representative non-treatment-seeking sample, as well as to
      determine whether these are similar to the personality correlates of other
      substance-related addictive disorders and whether individual differences in
      personality might account for the comorbidity between disordered gambling
      behavior and other substance-related addictive disorders. DESIGN: Longitudinal
      population-based study. PARTICIPANTS: A complete birth cohort of young adults
      born in Dunedin, New Zealand, between April 1, 1972, and March 31, 1973 (N = 939;
      475 men, 464 women). MAIN OUTCOME MEASURES: Multidimensional Personality
      Questionnaire assessments of personality were obtained at age 18 years;
      structured interview-based diagnoses of past-year problem gambling and alcohol,
      cannabis, and nicotine dependence were obtained at age 21 years. RESULTS: Problem
      gambling at age 21 years was associated with higher scores on the higher-order
      personality dimension of negative emotionality (d = 0.90) and with lower scores
      on the personality dimension of constraint (d = -0.72) measured at age 18 years
      compared with control subjects who did not have a past-year addictive disorder at
      age 21 years. Problem gambling was also associated with Multidimensional
      Personality Questionnaire indicators of risk-taking (d = 0.50) and impulsivity (d
      = 0.56). The personality profile associated with problem gambling was similar to
      the profiles associated with alcohol, cannabis, and nicotine dependence. The
      relations between problem gambling and the substance-related addictive disorders
      (odds ratios = 3.32-3.61) were reduced after controlling for individual
      differences in personality (odds ratios = 1.90-2.32). CONCLUSIONS: From the
      perspective of personality, problem gambling has much in common with the
      addictive disorders, as well as with the larger class of "externalizing" or
      "disinhibitory" disorders. Knowledge gained from the study of common personality
      underpinnings may be helpful in determining where disordered gambling behavior
      should reside in our diagnostic classification system.

PMID- 15997019
TI  - Predictors of treatment acceptance and completion in anorexia nervosa:
      implications for future study designs.
AB  - CONTEXT: There have been very few randomized controlled treatment studies of
      anorexia nervosa. OBJECTIVE: To evaluate factors leading to nonacceptance and
      noncompletion of treatment for 2 specific therapies and their combination in the
      treatment of anorexia nervosa. DESIGN: Randomized prospective study. SETTING:
      Weill-Cornell Medical Center, White Plains, NY; University of Minnesota,
      Minneapolis; and Stanford University, Stanford, Calif. Patients One hundred
      twenty-two patients meeting DSM-IV criteria for anorexia nervosa. INTERVENTIONS:
      Treatment with cognitive-behavioral therapy, fluoxetine hydrochloride, or their
      combination for 1 year. MAIN OUTCOME MEASURES: Dropout rate and acceptance of
      treatment (defined as staying in treatment at least 5 weeks). RESULTS: Of the 122
      randomized cases, 21 (17%) were withdrawn; the overall dropout rate was 46%
      (56/122) in the remaining patients. Treatment acceptance occurred in 89 (73%) of
      the 122 randomized cases. Of the 41 assigned to medication alone, acceptance
      occurred in 23 (56%). In the other 2 groups, acceptance rate was differentiated
      by high and low obsessive preoccupation scores (rates of 91% and 60%,
      respectively). The only predictor of treatment completion was high self-esteem,
      which was associated with a 51% rate of treatment acceptance. CONCLUSION:
      Acceptance of treatment and relatively high dropout rates pose a major problem
      for research in the treatment of anorexia nervosa. Differing characteristics
      predict dropout rates and acceptance, which need to be carefully studied before
      comparative treatment trials are conducted.

PMID- 15997020
TI  - White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor
      imaging study.
AB  - CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD)
      posit a primary role for dysfunction of the anterior cingulate gyrus. Both
      functional and structural neuroimaging studies have implicated anterior cingulate
      gray matter abnormalities in the pathophysiology of OCD, but there has been
      little investigation of the anterior cingulate white matter in this disorder.
      OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white
      matter microstructure in the anterior cingulate gyrus compared with healthy
      volunteers as inferred from diffusion tensor imaging. Additional analyses
      examined group differences in white matter integrity across the entire brain.
      DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of
      OCD and 15 healthy volunteers matched for age, sex, and handedness underwent
      diffusion tensor imaging and structural magnetic resonance imaging examinations.
      Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion,
      was compared between groups on a voxel-by-voxel basis in the anterior cingulate
      white matter after standardization in Talairach space. MAIN OUTCOME MEASURES:
      Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale)
      and FA. RESULTS: Compared with healthy volunteers, patients demonstrated
      significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus
      white matter. Additional analyses conducted across the rest of the brain white
      matter revealed lower FA bilaterally in the parietal region (supramarginal gyri),
      right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No
      areas of significantly higher FA were observed in patients compared with healthy
      volunteers. Lower FA in the parietal region correlated significantly with higher
      Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary
      findings provide evidence of an abnormality that involves the anterior cingulate
      white matter in the pathogenesis of OCD and are consistent with neurobiological
      models that posit a defect in connectivity in the anterior cingulate basal
      ganglia-thalamocortical circuit. White matter abnormalities in other brain
      regions may also be implicated in the neurobiology of OCD.

PMID- 15997022
TI  - Deficient fear conditioning in psychopathy: a functional magnetic resonance
      imaging study.
AB  - CONTEXT: Psychopaths belong to a larger group of persons with antisocial
      personality disorder and are characterized by an inability to have emotional
      involvement and by the repeated violation of the rights of others. It was
      hypothesized that this behavior might be the consequence of deficient fear
      conditioning. OBJECTIVE: To study the cerebral, peripheral, and subjective
      correlates of fear conditioning in criminal psychopaths and healthy control
      subjects. DESIGN: An aversive differential pavlovian delay conditioning paradigm
      with slides of neutral faces serving as conditioned and painful pressure as
      unconditioned stimuli. SETTING: The Department of Medical Psychology at the
      University of Tubingen, Tubingen, Germany. PARTICIPANTS: Ten male psychopaths as
      defined by the Hare Psychopathy Checklist-Revised and 10 age- and education
      matched healthy male controls. The psychopaths were criminal offenders on bail
      and waiting for their trial or were on parole. The healthy controls were
      recruited from the community. MAIN OUTCOME MEASURES: Brain activation based on
      functional magnetic resonance imaging, electrodermal responses, emotional
      valence, arousal, and contingency ratings. RESULTS: The healthy controls showed
      enhanced differential activation in the limbic-prefrontal circuit (amygdala,
      orbitofrontal cortex, insula, and anterior cingulate) during the acquisition of
      fear and successful verbal and autonomic conditioning. The psychopaths displayed
      no significant activity in this circuit and failed to show conditioned skin
      conductance and emotional valence ratings, although contingency and arousal
      ratings were normal. CONCLUSION: This dissociation of emotional and cognitive
      processing may be the neural basis of the lack of anticipation of aversive events
      in criminal psychopaths.

PMID- 15997021
TI  - Effects of antidepressant medication on morbidity and mortality in depressed
      patients after myocardial infarction.
AB  - BACKGROUND: Depression after myocardial infarction (MI) is associated with higher
      morbidity and mortality. Although antidepressants are effective in reducing
      depression, their use in patients with cardiovascular disease remains
      controversial. OBJECTIVE: To undertake a secondary analysis to determine the
      effects of using antidepressants on morbidity and mortality in post-MI patients
      who participated in the Enhancing Recovery in Coronary Heart Disease study.
      DESIGN: Observational secondary analysis. SETTING: Eight academic sites.
      PATIENTS: The Enhancing Recovery in Coronary Heart Disease clinical trial
      randomized 2481 depressed and/or socially isolated patients from October 1, 1996,
      to October 31, 1999. Depression was diagnosed using a structured clinical
      interview. This analysis was conducted on the 1834 patients enrolled with
      depression (849 women and 985 men). INTERVENTION: Use of antidepressant
      medication. MAIN OUTCOME MEASURES: Event-free survival was defined as the absence
      of death or recurrent MI. All-cause mortality was also examined. To relate
      exposure to antidepressants to subsequent morbidity and mortality, the data were
      analyzed using a time-dependent covariate model. RESULTS: During a mean follow-up
      of 29 months, 457 fatal and nonfatal cardiovascular events occurred. The risk of
      death or recurrent MI was significantly lower in patients taking selective
      serotonin reuptake inhibitors (adjusted hazard ratio [HR], 0.57; 95% confidence
      interval [CI], 0.38-0.84), as were the risk of all-cause mortality (adjusted HR,
      0.59; 95% CI, 0.37-0.96) and recurrent MI (adjusted HR, 0.53; 95% CI, 0.32-0.90),
      compared with patients who did not use selective serotonin reuptake inhibitors.
      For patients taking non-selective serotonin reuptake inhibitor antidepressants,
      the comparable HRs (95% CIs) were 0.72 (0.44-1.18), 0.64 (0.34-1.22), and 0.73
      (0.38-1.38) for risk of death or recurrent MI, all-cause mortality, or recurrent
      MI, respectively, compared with nonusers. CONCLUSIONS: Use of selective serotonin
      reuptake inhibitors in depressed patients who experience an acute MI might reduce
      subsequent cardiovascular morbidity and mortality. A controlled trial is needed
      to examine this important issue.

PMID- 15997023
TI  - The state of the world's children: Canada's paltry aid contribution.

PMID- 15997024
TI  - Kappa statistic.

PMID- 15997025
TI  - Beyond mythology.

PMID- 15997026
TI  - Money and medical education.

PMID- 15997027
TI  - Kappa statistic.

PMID- 15997028
TI  - Kappa statistic.

PMID- 15997029
TI  - More on India's HIV-1 epidemic.

PMID- 15997032
TI  - Problem gambling "like a new disease".

PMID- 15997033
TI  - Pressure mounts to expand screening of US newborns.

PMID- 15997034
TI  - Help wanted: McGill's dean of medicine.

PMID- 15997035
TI  - Canada lags on newborn screening.

PMID- 15997036
TI  - Trafficking in women: the Canadian perspective.

PMID- 15997037
TI  - How the gut expels parasites: new clues.

PMID- 15997038
TI  - Use of polysomnography with synchronized digital video recording to diagnose
      pediatric sleep breathing disorders.

PMID- 15997039
TI  - Safe handling of food at home or cottage.

PMID- 15997041
TI  - Scalp lesions in a 78-year-old woman.

PMID- 15997042
TI  - Population rates of cardiac catheterization and yield of high-risk coronary
      artery disease.
AB  - BACKGROUND: The optimal population rate of cardiac catheterization is unknown.
      One potential way to determine it would be to examine whether there is a
      population rate beyond which the yield of high-risk coronary artery disease (CAD)
      does not rise. METHODS: Using a detailed clinical registry that captures all
      patients undergoing cardiac catheterization in Alberta, we determined annual
      population rates of cardiac catheterization and the corresponding yield of cases
      of high-risk CAD in each of Alberta's 17 health regions from 1995 to 2002. Least
      squares linear regression analysis and hierarchical modelling methods were then
      used to assess the linear relation between catheterization rates and rates of
      high-risk CAD. RESULTS: The age-adjusted average rate of cardiac catheterization
      among men ranged from 404.9 to 638.1 per 100,000 population aged over 20 years.
      Among women, the average rate ranged from 171.8 to 314.0 per 100,000. For both
      sexes, increased regional rates of catheterization were associated with a
      linearly increasing yield of high-risk CAD, with no evidence of a plateau in
      yield when more procedures were performed. One additional case of high-risk CAD
      was identified for every 2.5 additional cardiac catheterization procedures
      performed among men, and for every 3.7 additional procedures performed among
      women. INTERPRETATION: The increasing yield of patients with high-risk CAD
      associated with increased regional population rates of cardiac catheterization,
      together with the absence of a plateau in yield, suggests that Alberta's
      population rates of cardiac catheterization are suboptimal to detect people with
      high-risk CAD.

PMID- 15997043
TI  - Impact of care at a multidisciplinary congestive heart failure clinic: a
      randomized trial.
AB  - BACKGROUND: Although multidisciplinary congestive heart failure clinics in the
      United States appear to be effective in reducing the number of hospital
      readmissions, it is unclear whether the same benefit is seen in countries such as
      Canada, where access to both general and specialized medical care is free and
      unrestricted. We sought to determine the impact of care at a multidisciplinary
      specialized outpatient congestive heart failure clinic compared with standard
      care. METHODS: We randomly assigned 230 eligible patients who had experienced an
      acute episode of congestive heart failure to standard care (n = 115) or follow-up
      at a multidisciplinary specialized heart failure outpatient clinic (n = 115). The
      intervention consisted of a structured outpatient clinic environment with
      complete access to cardiologists and allied health professionals. The primary
      outcomes were all-cause hospital admission rates and total number of days in
      hospital at 6 months. The secondary outcomes were total number of emergency
      department visits, quality of life and total mortality. RESULTS: At 6 months,
      fewer patients in the intervention group had required readmission to hospital
      than patients in the control group (45 [39%] v. 66 [57%], crude hazard ratio [HR]
      0.59, 95% confidence interval [CI] 0.38-0.92. Patients in the intervention group
      stayed in hospital for 514 days compared with 815 days required by patients in
      the control group (adjusted HR 0.56, 95% CI 0.35-0.89). The number of patients
      seen in the emergency department and the total number of emergency department
      visits were similar in the intervention and control groups. At 6 months, quality
      of life, which was self-assessed using the Minnesota Living with Heart Failure
      questionnaire, was unchanged in the control group but improved in the
      intervention group (p < 0.001). No difference in mortality was observed, with 19
      deaths in the control group and 12 in the intervention group (HR 0.61, 95% CI
      0.24-1.54). INTERPRETATION: Compared with usual care, care at a multidisciplinary
      specialized congestive heart failure outpatient clinic reduced the number of
      hospital readmissions and hospital days and improved quality of life. When our
      results are integrated with those from other, similar trials, multidisciplinary
      disease management strategies for congestive heart failure are associated with
      clinically worthwhile improvements in survival.

PMID- 15997044
TI  - Determining optimal population rates of cardiac catheterization: a phantom
      alternative?

PMID- 15997045
TI  - Multidisciplinary heart failure clinics: are they effective in Canada?

PMID- 15997047
TI  - Aerobic capacity, strength, flexibility, and activity level in unimpaired
      extremely low birth weight (<or=800 g) survivors at 17 years of age compared with
      term-born control subjects.
AB  - OBJECTIVES: To compare aerobic capacity, strength, flexibility, and activity
      level in extremely low birth weight (ELBW) adolescents at 17 years of age with
      term-born control subjects. METHODS: Fifty-three ELBW teens of birth weight
      <or=800 g were assessed at 17.3 years (16.3-19.7 years; birth weight: 720 g [520
      800 g]; gestation: 26 weeks [23-29 weeks]) along with term-born control subjects
      (n = 31) at age 17.8 years (16.5-19.0 years; birth weight: 3506 g [3068-4196 g];
      gestation: weeks 40 [39-42 weeks]). ELBW and control teens were assessed by a
      pediatric physiotherapist and completed components of the Canadian Physical
      Activity, Fitness and Lifestyle Appraisal and a self-assessment fitness and
      activity questionnaire. Continuous data were analyzed using MANOVA (group,
      gender) followed by t tests; categorical data were analyzed using the chi(2)
      test. RESULTS: ELBW teens had lower aerobic capacity, grip strength, leg power,
      and vertical jump; could do fewer push-ups; had less abdominal strength as
      measured by curl-ups; had less lower back flexibility; and had tighter
      hamstrings. ELBW teens reported less previous and current sports participation,
      lower physical activity level, and poorer coordination compared with term-born
      control subjects. ELBW teens were also found to have more difficulty with
      maintenance of rhythm and cadence. Although ELBW teens rated themselves lower on
      all measures of sporting activity, they were as happy with their level of fitness
      as the control subjects. CONCLUSIONS: Compared with term-born control subjects,
      there are significant differences in motor performance in unimpaired ELBW
      survivors in late adolescence, reflected in aerobic capacity, strength,
      endurance, flexibility, and activity level. We conclude that these differences in
      fitness and physical activity are related to the interaction of effects of
      premature birth on the motor system together with a more inactive lifestyle.
      These findings have potential implications for later adult health problems.

PMID- 15997048
TI  - La5Mo6O21: a novel ternary reduced molybdenum oxide containing {MoIV}3 clusters
      and isolated MoV centres.
AB  - The crystal structure of La5Mo6O21 (pentalanthanum hexamolybdenum henicosaoxide)
      is made up of Mo3O13 units containing triangular {MoIV}3 clusters, three
      distorted MoVO6 octahedral units and six interstitial LaIII atoms. The Mo3O13
      unit consists of three edge-sharing MoIVO6 units involving Mo-Mo bonding. The
      three MoVO6 octahedra share their corners or edges with each other and with the
      Mo3O13 units.

PMID- 15997046
TI  - Bordetella pertussis: the intersection of genomics and pathobiology.
AB  - There has been much recent concern over an increasing incidence of pertussis
      despite high levels of vaccine coverage of infants. Many reports have documented
      that much of the increased incidence is due to infection in adolescents and
      adults. This renewal of interest in pertussis comes at a time when the findings
      of the Bordetella genome project have led to a quantum leap forward in our
      understanding of the biology, evolution and pathogenesis of the bacterium
      responsible for the disease. The impact of this basic research on current
      clinical problems posed by B. pertussis infection is discussed.

PMID- 15997049
TI  - Sm5Ga3.
AB  - Single crystals of pentasamarium trigallium, Sm5Ga3, display tetragonal symmetry.
      The crystal structure was solved and refined in space group P4/ncc. The present
      work does not confirm the space group I4/mcm previously deduced from powder data
      measurements. One Sm atom is in a general position, and the other Sm atom and one
      of the Ga atoms are at sites with fourfold symmetry. The remaining Ga atom is at
      a site with twofold symmetry.

PMID- 15997050
TI  - Potassium cerium(III) bis(sulfate) monohydrate, KCe(SO4)2.H2O.
AB  - The crystal structure of potassium cerium(III) bis(sulfate) monohydrate,
      KCe(SO4)2.H2O, is built up from irregular independent SO4 tetrahedra, CeO9
      polyhedra in the form of distorted tricapped trigonal prisms and K+ ions.
      Hydrogen bonding between the free water molecule and sulfate groups supplement
      the ionic bonds characteristic of the rest of the structure.

PMID- 15997051
TI  - Thallium(III) selenite, Tl2(SeO3)3.
AB  - The structure of Tl2(SeO3)3 [dithallium(III) triselenium(IV) nonaoxide] is
      monoclinic (P21/n symmetry), with all atoms in general positions. It is built up
      from TlO6 octahedra, distorted TlO7 pentagonal bipyramids and (SeO3)2- pyramids
      sharing vertices and edges to form corrugated (001) layers. The Se lone pairs of
      electrons are accommodated in the interlayer regions.

PMID- 15997052
TI  - Sodium calcium orthovanadate, NaCa4(VO4)3.
AB  - Single crystals of sodium tetracalcium trivanadium dodecaoxide were prepared by
      melting a powder sample of NaCa4(VO4)3 at 1673 K, followed by slow cooling to
      room temperature. The compound crystallizes in the Pnma space group and is
      isostructural with the mineral silicocarnotite, Ca5(PO4)2SiO4. The structure is
      composed of isolated VO4 tetrahedra linked by sodium and calcium cations
      disordered over eight- and seven-coordinated sites.

PMID- 15997053
TI  - (Mu-tri-tert-butoxysilanethiolato)bis[(tetrahydrofuran)lithium(I)] and catena
      poly[[bis(mu-tri-tert-butoxysilanethiolato)dilithium(I)]-mu-dimethoxyethane]:
      solvent coordination as the structure-forming factor.
AB  - The title compounds, mu-(tri-tert-butoxysilanethiolato-kappa2S:S)
      bis[(tetrahydrofuran-kappaO)lithium(I)], [Li2(C12H27O3SSi)2(C4H8O)2], (I), and
      catena-poly[[bis(mu-tri-tert-butoxysilanethiolato)-1:2kappa(2)S;1kappaS:2kappaS,O
      dilithium(I)]-mu-dimethoxyethane-kappa2O:O'], [Li2(C12H27O3SSi)2(C4H10O2)]n,
      (II), were obtained by the reaction of tri-tert-butoxysilanethiol with metallic
      lithium. The crude product, when recrystallized from tetrahydrofuran (THF) yields
      (I), and when recrystallized from 1,2-dimethoxyethane (DME) gives (II). Compound
      (I) forms centrosymmetric dimers in the solid state with an Li2S2 central core,
      whereas (II) forms infinitely long chains, in which the centrosymmetric dimeric
      units are linked together by the bidentate DME ligand (also residing on an
      inversion centre), thus forming a coordination polymer. The formation of a one
      dimensional structure in (II) is a consequence of replacement of a monodentate
      THF solvent molecule with a bidentate DME molecule.

PMID- 15997054
TI  - Diaqua[N,N'-bis(5-methoxysalicylidene)ethylenediaminato
      kappa(4)O,N,N',O']manganese(III) perchlorate, aqua[N,N'-bis(3,5
      dichlorosalicylidene)ethylenediaminato-kappa4O,N,N',O'](methanol
      kappaO)manganese(III) perchlorate and bis[mu-N,N'-bis(3
      methoxysalicylidene)ethylenediaminato-kappa5O,N,N',O':O]bis[(methanol
      kappaO)manganese(III)] diperchlorate.
AB  - The title compounds, a hydrogen-bonded linear chain, [Mn(C18H18N2O4)(H2O)2]ClO4,
      (I), a hydrogen-bonded pseudo-dimer, [Mn(C16H10Cl4N2O2)(CH4O)(H2O)]ClO4, (II),
      and a dimer, [Mn2(C18H18N2O4)2(CH4O)2](ClO4)2, (III), respectively, have been
      structurally characterized. The three complexes are completely different in their
      structural features, despite identical counter-anions and only slight
      modification of the substituents in the ligands. Complex (I) affords an elongated
      octahedral coordination environment, with axial Mn-O(water) distances of 2.259
      (3) and 2.313 (3) A, which forms hydrogen-bonded linear chains along the
      crystallographic c axis. Hydrogen-bonded pseudo-dimeric compound (II) also
      affords an elongated octahedral coordination environment, with axial Mn-O(CH3OH)
      = 2.222 (3) A and Mn-O(water) = 2.266 (3) A. Dimeric complex (III) is
      centrosymmetric and consists of distorted octahedral Mn atoms, with axial Mn
      O(CH3OH) = 2.242 (2) A and Mn-O(phenolate) = 2.348 (1) A, connected via bridging
      O atoms from one of the ligands. The magnetic properties of the three complexes
      are described.

PMID- 15997055
TI  - Two novel bis(2,9-dimethyl-1,10-phenanthroline)copper(I) complexes:
      [Cu(dmp)2]2(PF6)2.0.5(bpmh).CH3CN and [Cu(dmp)2][N(CN)2].
AB  - Two new salts of the cation [CuI(dmp)2]+ (dmp is 2,9-dimethyl-1,10
      phenanthroline, C14H12N2), namely bis[bis(2,9-dimethyl-1,10-phenanthroline
      kappa2N,N')copper(I)] bis(hexafluorophosphate) hemi[bis(4
      pyridylmethylidene)hydrazine] acetonitrile solvate,
      [Cu(C14H12N2)2]2(PF6)2.0.5C12H10N4.C2H3N or [Cu(dmp)2]2(PF6)2.0.5(bpmh).CH3CN
      [bpmh is bis(4-pyridylmethylidene)hydrazine, C12H10N4], (I), and bis(2,9-dimethyl
      1,10-phenanthroline-2N,N')copper(I) dicyanamide, [Cu(C14H12N2)2](C2N3) or
      [Cu(dmp)2][N(CN)2], (II), are reported. The Cu-N bond lengths and the distortion
      from idealized tetrahedral geometry of the dmp ligands are discussed and compared
      with related compounds. The bpmh molecule in (I) is pi-pi stacked with a dmp
      ligand at a distance of 3.4 A, rather than coordinated to the metal atom. The
      molecule lies across an inversion center in the crystal. In (II), the normally
      coordinated dicyanamide molecule is present as an uncoordinated counter-ion.

PMID- 15997056
TI  - A novel three-dimensional copper(II) coordination polymer with 1,4-bis(1,2,4
      triazol-1-ylmethyl)benzene and thiocyanate.
AB  - In the title complex, poly[copper(II)-di-2-thiocyanato-2-1,4-bis(1,2,4-triazol-1
      ylmethyl)benzene], [Cu(NCS)2(C12H12N6)]n, the CuII atom lies on an inversion
      centre in a tetragonally distorted octahedral environment. Four N atoms from
      thiocyanate and 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene (bbtz) ligands fill the
      equatorial positions, and S atoms from symmetry-related thiocyanate ligands fill
      the axial positions. The benzene ring of the bbtz ligand lies about an inversion
      centre. Single thiocyanate bridges link the CuII atoms into two-dimensional
      sheets containing an unprecedented 16-membered [Cu4(-NCS-N:S)4] ring. The bbtz
      ligands further link the two-dimensional sheets into a three-dimensional network.

PMID- 15997057
TI  - The new polynuclear titanium(IV) complex [(Cp*TiCl)(mu-O)2(Cp*Ti)2(mu-O)(mu
      O)2]2Ti (Cp* is eta5-C5Me5).
AB  - A new polynuclear titanium(IV) complex, dichlorodeca-mu2-oxo
      hexakis(pentamethylcyclopentadienyl)hexatitanium(IV), [Ti6(C10H15)6Cl2O10], has
      been synthesized by hydrolysis of a titanium complex bearing an N-(2-hydroxy-3,5
      dimethylbenzyl)diethanolamine Mannich ligand. The molecule has two O-bridged
      Ti3O3 rings linked to two similar rings through a tetrahedrally O-coordinated Ti
      atom. All Ti atoms except the central one are coordinated to
      pentamethylcyclopentadienyl (Cp*) ligands. The Cp* ligands are arranged with
      approximate symmetry with respect to the Ti/O/Cl core.

PMID- 15997058
TI  - catena-Poly[[{4-bromo-2-[2-(dimethylamino)ethyliminomethyl]phenolato}copper(II)]
      mu-azido].
AB  - The title complex, [Cu(C11H14BrN2O)(N3)]n, is an interesting azide-bridged
      polynuclear copper(II) compound. The Cu(II) atom is five-coordinated in a square
      pyramidal configuration, with one O and two N atoms of one Schiff base and one
      terminal N atom of a bridging azide ligand defining the basal plane, and another
      terminal N atom of another bridging azide ligand occupying the axial position.
      The {4-bromo-2-[2-(dimethylamino)ethyliminomethyl]phenolato}copper(II) moieties
      are linked by the bridging azide ligands, forming polymeric chains running along
      the b axis. Adjacent chains are further linked by weak Br...Br interactions into
      a sheet.

PMID- 15997059
TI  - Diacetatobis(2-aminobenzothiazole-kappaN)cobalt(II).
AB  - The title complex, [Co(C2H3O2)2(C7H6N2S)2], contains a Co centre with a slightly
      distorted tetrahedral coordination geometry, involving two acetate ligands and
      two N atoms from the thiazole moiety [Co-O = 2.0025 (14) and 1.9953 (16) A, and
      Co-N = 2.0524 (18) and 2.0568 (18) A]. The interplanar angle between the two
      benzothiazole moieties is 77.86 (3) degrees . The amine groups, acting as donors,
      participate in intra- and intermolecular N-H...O hydrogen bonds, with N...O
      distances in the range 2.806 (2)-2.857 (2) A.

PMID- 15997060
TI  - Ethylenediaminium niobium oxyfluoride.
AB  - The title compound, bis(ethylenediaminium) mu-oxo-bis[tetrafluorooxoniobium(V)],
      (C2H10N2)2[Nb2O3F8], is a novel organically templated niobium oxyfluoride. It
      consists of isolated [Nb2O3F8]4- octahedral dimers charge balanced by
      ethylenediaminium cations, two of which lie about inversion centres. Two NbO2F4
      octahedra are fused through a common O atom to form the dimers. Characteristic
      short terminal Nb=O bond lengths and longer Nb-F and bridging Nb-O bond lengths
      are observed, which result in the out-of-centre distortion of the octahedra, a
      manifestation of the second-order Jahn-Teller effect. Extensive hydrogen bonding
      between the dimers and the organic template is exhibited.

PMID- 15997061
TI  - A mixed iron(III)/lithium alkoxide.
AB  - The heterometallic alkoxide catena-poly[[tetra-mu2-tert-butoxo
      1:2kappa4O:O;1:3kappa4O:O-bis(tetrahydrofuran)-2kappaO,3kappaO
      iron(III)dilithium(I)]-mu-bromo], [FeLi2Br(C4H9O)4(C4H8O)2]n, forms a one
      dimensional chain through an a-glide. This conformation is achieved through the
      formation of Fe(III)/O/Li/O rings and Li-Br-Li bridges.

PMID- 15997062
TI  - Poly[[diaquabarium(II)]-mu5-m-phenylenedioxydiacetato]: a three-dimensional
      barium(II) coordination polymer.
AB  - In the title coordination polymer, [Ba(1,3-BDOA)(H2O)2]n (where 1,3-BDOA2- is the
      m-phenylenedioxydiacetate dianion, C10H8O6), each Ba(II) ion is ten-coordinated
      by six carboxyl O atoms and two ether O atoms from different 1,3-BDOA(2-)
      ligands, as well as by two water molecules, thus defining a dodecahedron. The
      Ba(II) atoms are covalently linked by 1,3-BDOA2- ligands in different
      crystallographic directions, giving rise to a three-dimensional open framework.
      The crystal structure is further stabilized by hydrogen bonds and pi-pi stacking
      interactions. In previously studied polymers of this type, the 1,3-BDOA2- ligand
      showed multiple bridging modes with metal ions, including bi-, tri-, tetra- and
      hexadentate. The title Ba(II) complex represents a novel three-dimensional
      coordination polymer constructed by octadentate bridging 1,3-BDOA2- ligands.

PMID- 15997063
TI  - Bis{1-[N-(2-methoxyphenyl)iminomethyl]naphthalen-2(1H)-onato
      kappa3O,N,O'}zinc(II) ethanol solvate.
AB  - In the crystal structure of the title compound, [Zn(C18H14NO2)2].C2H6O, the Zn
      atom displays a highly distorted octahedral coordination involving the O and N
      atoms of two molecules of the Schiff base 1-[N-(2
      methoxyphenyl)iminomethyl]naphthalen-2(1H)-one, which acts as an O,N,O'
      tridentate ligand. The ethanol molecule is bound to the methoxy group of one
      ligand molecule via a hydrogen bond.

PMID- 15997064
TI  - Low-dimensional compounds containing cyano groups. XII. Bis(1,3-diaminopropane
      kappa2N,N')(dicyanamido-kappaNPart XI: Potocnak, Burcak, Baran and Jager
      (2005).)copper(II) perchlorate.
AB  - The title compound, [Cu(C2N3)(C3H10N2)2]ClO4, is made up of [Cu(tn)2{N(CN)2}]+
      complex cations (tn is 1,3-diaminopropane) and ClO4- anions. The Cu(II) atom is
      coordinated by four N atoms of two equatorial tn ligands, with an average
      distance of 2.041 (7) A, and one nitrile N atom of the dicyanamide anion in an
      axial position, at a distance of 2.236 (3) A, in a manner approaching square
      planar coordination geometry. The complex has C(s) symmetry, with the mirror
      plane lying through the central C atoms of both tn ligands and the dca ligand.
      The ClO4- anion might be considered as very weakly coordinated in the opposite
      axial position [Cu-O = 2.705 (3) A], thus completing the Cu(II) coordination to
      asymmetric elongated octahedral (4+1+1*). The Cu atom and the perchlorate anion
      both lie on mirror planes.

PMID- 15997066
TI  - Bis[mu-N,N'-bis(3-methylsalicylidene)propane-1,3-diaminato]dicobalt(II) 0.28
      hydrate.
AB  - The title complex, bis{mu-6,6-dimethyl-2,2'-[propane-1,3
      diylbis(nitrilomethylidyne)]diphenolato}dicobalt(II) 0.28-hydrate,
      [Co2(C19H20N2O2)2].0.28H2O, is a dinuclear cobalt(II) complex, which crystallizes
      in the tetragonal space group P4(1)2(1)2. The complex molecule is located on a
      twofold symmetry axis. Each Co(II) ion is five-coordinated by two O and two N
      atoms from a Schiff base ligand, and by another bridging phenolate O atom from
      another Schiff base ligand, giving a severely distorted trigonal-bipyramidal
      coordination environment.

PMID- 15997065
TI  - Second-sphere coordination in anion binding: sodium hexaamminecobalt(III)
      tetrakis(4-fluorobenzoate) monohydrate.
AB  - In sodium hexaamminecobalt(III) tetrakis(4-fluorobenzoate) monohydrate,
      Na[Co(NH3)6](C7H4FO2)4.H2O, determined at 180 K, [Co(NH3)6]3+ cations lie on
      centres of inversion and form layers in which their C4 axes lie perpendicular to
      the layer planes. 4-Fluorobenzoate anions lie on twofold axes and general
      positions and adopt near-planar geometries. Na+ cations and water molecules lie
      on twofold axes, forming [NaO5] square pyramids that lie between the [Co(NH3)6]3+
      cations. The second-sphere interactions between [Co(NH3)6]3+ cations and 4
      fluorobenzoate anions comprise edge-to-face and vertex-to-face arrangements. The
      structure is closely comparable with that of the benzoic acid salt, demonstrating
      that fluorination of the anion in the para position has no significant influence
      on the second-sphere interactions and minimal influence on the gross crystal
      structure.

PMID- 15997067
TI  - Magnetic properties of two double-layer structures built from hydroxynaphthoic
      acids and manganese.
AB  - Double-layer structures consisting of alternating polar and non-polar layers have
      been prepared using Mn2+ ions and o-hydroxynaphthoic acids. The polar layers
      contain the Mn2+ ions, carboxylate groups, hydroxy groups and water molecules.
      The non-polar layers are built up from the naphthalene moieties. In catena
      poly[[diaquamanganese(II)]bis(mu-3-hydroxy-2-naphthoato-kappa2O:O')] (also called
      manganese 3-hydroxy-2-naphthoate dihydrate), [Mn(C11H7O3)2(H2O)2]n, (I), the Mn2+
      ions are connected by carboxylate groups to form two-dimensional networks. This
      compound shows distinct antiferromagnetic interactions and long-range ordering at
      low temperature. In contrast, tetraaquabis(1-hydroxy-2-naphthoato
      kappaO)manganese(II), [Mn(C11H7O3)2(H2O)4], (II), which lacks a close linkage
      between the Mn2+ ions, reveals purely paramagnetic behaviour. In (II), the Mn2+
      ion lies on an inversion centre.

PMID- 15997068
TI  - Methyl 2-(4-ferrocenylbenzamido)thiophene-3-carboxylate and ethyl 2-(4
      ferrocenylbenzamido)-1,3-thiazole-4-acetate, a unique ferrocene derivative
      containing a thiazole moiety.
AB  - The conformations and hydrogen bonding in the thiophene and thiazole title
      compounds, [Fe(C5H5)(C20H14NO3S)], (I), and [Fe(C5H5)(C19H17N2O3S)], (II), are
      discussed. The sequence (C5H4)-(C6H4)-(CONH)-(C4H2S)-(CO2Me) of rings and
      moieties in (I) is close to being planar; all consecutive interplanar angles are
      less than 10 degrees . An intramolecular N-H...O=C(ester) hydrogen bond [graph
      set S6, N...O = 2.768 (2) A and N-H...O = 134 (2) degrees ] effects the molecular
      planarity, and aggregation occurs via hydrogen-bonded chains formed from
      intermolecular C(ar)-H...O=C(ester/amide) interactions along [010], with C...O
      distances ranging from 3.401 (3) to 3.577 (2) A. The thiazole system in (II)
      crystallizes with two molecules in the asymmetric unit; these differ in the
      conformation along their long molecular axes; for example, the interplanar angle
      between the phenylene (C6H4) and thiazole (C3NS) rings is 8.1 (2) degrees in one
      molecule and 27.66 (14) degrees in the other. Intermolecular N-H...O=C(ester)
      hydrogen bonds [N...O = 2.972 (4) and 2.971 (3) A], each augmented by a
      C(phenylene)-H...O=C(ester) interaction [3.184 (5) and 3.395 (4) A], form motifs
      with graph set R2(1)(7) and generate chains along [100]. The amide C=O groups do
      not participate in hydrogen bonding. Compound (II) is the first reported
      ferrocenyl-containing thiazole structure.

PMID- 15997069
TI  - Bis(2-butyl-N,N'-diisopropylamidinato)dichlorohafnium(IV).
AB  - The title compound, [Hf(C11H23N2)2Cl(2)], is a monomeric hafnium(IV) complex
      containing two bidentate amidinate ligands and two cis Cl atoms. The crystals are
      triclinic (space group P-1) and there is one independent six-coordinate monomer
      with a highly distorted octahedral geometry in the asymmetric unit. The reported
      structure is the first hafnium-amidinate complex to be characterized successfully
      by single-crystal X-ray diffraction.

PMID- 15997070
TI  - 2-acetamido-N-benzyl-2-(methoxyamino)acetamides: functionalized amino acid
      anticonvulsants.
AB  - In the crystal structure of 2-acetamido-N-benzyl-2-(methoxyamino)acetamide (3L),
      C12H17N3O3, the 2-acetylaminoacetamide moiety has a linearly extended
      conformation, with an interplanar angle between the two amide groups of 157.3 (1)
      degrees . In 2-acetamido-N-benzyl-2-[methoxy(methyl)amino]acetamide (3N),
      C13H19N3O3, the planes of the two amide groups intersect at an angle of 126.4 (4)
      degrees , resulting in a chain that is slightly more bent. The replacement of the
      methoxyamino H atom of 3L with a methyl group to form 3N and concomitant loss of
      hydrogen bonding results in some positional/thermal disorder in the
      methoxy(methyl)amino group. In both structures, in addition to classical N-H...O
      hydrogen bonds, there are also weak non-standard C-H...O hydrogen bonds. The
      hydrogen bonds and packing interactions result in planar hydrophilic and
      hydrophobic areas perpendicular to the c axis in 3L and parallel to the ab plane
      in the N-methyl derivative. Stereochemical comparisons with phenytoin have
      identified two O atoms and a phenyl group as molecular features likely to be
      responsible for the anticonvulsant activities of these compounds.

PMID- 15997071
TI  - L-alanylglycyl-L-alanine monohydrate at 20 K.
AB  - The X-ray crystal structure of the title compound, C8H15N3O4.H2O, at 20 K (space
      group P2(1)) reveals that the molecular conformation of the tripeptide is
      remarkably different from the water-free form (space group P2(1)2(1)2(1))
      reported previously [Padiyar & Seshadri (1996), Acta Cryst. C52, 1693-1695].

PMID- 15997072
TI  - (E)-4-methoxybenzaldehyde O-(N-phenylcarbamoyl)oxime.
AB  - There are two molecules, C15H14N2O3, in the asymmetric unit of the title
      compound, the first structurally characterized carbamoyl benzaldehyde oxime
      derivative; these molecules do not differ significantly. Intermolecular N-H...O
      hydrogen bonds connect molecules into infinite ...ABAB... ribbons along the [100]
      direction.

PMID- 15997073
TI  - N-[tert-Butoxycarbonylglycyl-(Z)-alpha,beta-dehydrophenylalanylglycyl-(E)
      alpha,beta-dehydrophenylalanylphenylalanyl]-4-nitroaniline ethanol solvate.
AB  - The alpha,beta-dehydrophenylalanine residues influence the conformation of the
      title pentapeptide Boc0-Gly1-Delta(Z)Phe2-Gly3-Delta(E)Phe4-L-Phe5-p-NA ethanol
      solvate, C42H43N7O9.C2H5OH. The first unsaturated phenylalanyl (Delta(Z)Phe2) and
      the third glycyl (Gly3) residues form a type I beta turn, while the second
      unsaturated phenylalanyl (Delta(E)Phe4) and the last phenylalanyl (L-Phe5)
      residues are part of a type II beta turn. All the amino acids in the peptide are
      linked trans to one another. The crystal structure is stabilized by intra- and
      intermolecular hydrogen bonds.

PMID- 15997074
TI  - Stereochemical basis for activity in thiadiazole anticonvulsants: 1-[5-(biphenyl
      2-yl)-1,3,4-thiadiazol-2-yl]methanaminium chloride and two inactive analogues, 2
      (biphenyl-4-yl)-5-[2-(1-methylethylidene)hydrazino]-1,3,4-thiadiazole and the
      methanol solvate of its hydrochloride salt.
AB  - In 1-[5-(biphenyl-2-yl)-1,3,4-thiadiazol-2-yl]methanaminium chloride,
      C15H14N3S+.Cl-, the protonation occurs at the amine N atom. The outer phenyl ring
      makes an angle of 88.0 (2) degrees with the plane through the inner benzene ring,
      and the planes of the thiadiazole ring and the attached benzene ring intersect at
      an angle of 165.5 (4) degrees . In addition to classical N-H...N and N-H...Cl(-)
      hydrogen bonds producing chains parallel to the c axis, there are weak C-H...N
      and C-H...Cl- hydrogen bonds. The hydrogen bonds and packing interactions result
      in hydrophilic and hydrophobic planar areas in the crystal, perpendicular to the
      a axis. Stereochemical comparison with phenytoin shows that the two compounds may
      utilize similar mechanisms of action. 2-(Biphenyl-4-yl)-5-[2-(1
      methylethylidene)hydrazino]-1,3,4-thiadiazole, C17H16N4S, where Z' = 2, and the
      methanol solvate of its hydrochloride salt, 5-(biphenyl-4-yl)-2-[2-(1
      methylethylidene)hydrazino]-1,3,4-thiadiazol-3-ium chloride methanol solvate,
      C17H17N4S+.Cl-.CH3OH, adopt linear almost planar molecular conformations. The
      para position of the outer phenyl ring in these compounds precludes adoption of
      the phenytoin anticonvulsant stereochemistry.

PMID- 15997075
TI  - 1,4,7,10-tetraoxacyclododecane-triphenylmethanethiol (1/2).
AB  - In the centrosymmetric formula unit of the title complex, C8H16O4.2C18H16S, the
      1,4,7,10-tetraoxacyclododecane molecule adopts the biangular [66] conformation,
      and the triphenylmethanethiol molecules are linked to the macrocycle via a long S
      H...O hydrogen bond [S...O = 3.460 (2) A and S-H...O = 161 (2) degrees].
      Attractive interactions of phenyl groups in edge-to-face conformations combine
      inversion-related formula units into chains running along the [111] direction in
      the crystal structure. Association of the chains into sheets is achieved via C
      H...pi interactions.

PMID- 15997076
TI  - The twofold interpenetrated three-connected three-dimensional (10,3)-net in 2
      aminoethene-1,1,2-tricarbonitrile.
AB  - In the crystal structure of the title compound, C5H2N4, each molecule is linked
      by N-H...N[triple-bond]C hydrogen bonds to four other molecules, thus forming a
      network that can be described as a twofold interpenetrated three-connected three
      dimensional (10,3)-net. The interpenetrated nets are related by (010)
      translation. If only intermolecular hydrogen bonds are taken into account, these
      nets can be considered as independent. However, the interactions between the
      cyano groups from different nets indicate mutual assistance of the two nets
      during their formation.

PMID- 15997077
TI  - C-H...O, C-H...pi and pi-pi interactions in three benzofuran-2-yl ketone
      derivatives.
AB  - The molecules of 2-benzoyl-1-benzofuran, C15H10O2, (I), interact through double C
      H...O hydrogen bonds, forming dimers that are further linked by C-H...O, C-H...pi
      and pi-pi interactions, resulting in a three-dimensional supramolecular network.
      The dihedral angle between the benzoyl and benzofuran fragments in (I) is 46.15
      (3) degrees . The molecules of bis(5-bromo-1-benzofuran-2-yl) ketone, C17H8Br2O3,
      (II), exhibit C2 symmetry, with the carbonyl group (C=O) lying along the twofold
      rotation axis, and are linked by a combination of C-H...O and C-H...pi
      interactions and Br...Br contacts to form sheets. The stability of the molecular
      packing in 3-mesityl-3-methylcyclobutyl 3-methylnaphtho[1,2-b]furan-2-yl ketone,
      C28H28O2, (III), arises from C-H...pi and pi-pi stacking interactions. The fused
      naphthofuran moiety in (III) is essentially planar and makes a dihedral angle of
      81.61 (3) degrees with the mean plane of the trimethylbenzene ring.

PMID- 15997078
TI  - A monoclinic polymorph of 3,7,7-trimethyl-1-phenyl-5,6,7,8-tetrahydro-1H
      pyrazolo[3,4-b]quinolin-5-one.
AB  - A second, monoclinic, polymorph of the title compound, C19H19N3O, is reported. In
      this polymorph, the molecules are linked into chains by paired C-H...pi hydrogen
      bonds and the chains are linked into sheets by pi stacking interactions.

PMID- 15997079
TI  - Solvent-dependent polymorphism in isomeric N-(nitrobenzylidene)iodoanilines.
AB  - Three of the nine isomeric N-(nitrobenzylidene)iodoanilines, C13H9IN2O2, have
      been found, when crystallized from acetone, to yield polymorphs which differ from
      those obtained upon crystallization from ethanol. In the second polymorph of 2
      iodo-N-(2-nitrobenzylidene)aniline, the molecules are disordered across inversion
      centres in space group C2/c, but there are no direction-specific interactions
      between the molecules. In the second polymorph of 2-iodo-N-(3
      nitrobenzylidene)aniline, the molecules adopt a different conformation from those
      in the first polymorph, and they are linked into sheets by a combination of a
      three-centre iodo-nitro interaction and an aromatic pi-pi stacking interaction,
      both of which are absent from the supramolecular structure of the first
      polymorph. The second polymorph of 3-iodo-N-(2-nitrobenzylidene)aniline
      crystallizes with Z' = 2 in space group P2(1), and the molecules are linked into
      sheets by one C-H...O hydrogen bond and two C-H...pi(arene) hydrogen bonds.

PMID- 15997080
TI  - 2-Iodo-N-(4-nitrophenyl)benzamide forms hydrogen-bonded sheets of R4(4)(24)
      rings.
AB  - Molecules of the title compound, C13H9IN2O3, are linked into C4 chains by an N
      H...O=C hydrogen bond, and these chains are linked into sheets of R4(4)(24) rings
      by means of a C-H...O-N hydrogen bond. However, C-H...pi(arene) hydrogen bonds,
      and pi-pi stacking and iodo-nitro interactions are all absent.

PMID- 15997081
TI  - Hydrogen-bonded chains in isostructural 5-methyl-2-(4-methylphenyl)-7,8-dihydro
      6H-cyclopenta[g]pyrazolo[1,5-a]pyrimidine, 2-(4-chlorophenyl)-5-methyl-7,8
      dihydro-6H-cyclopenta[g]pyrazolo[1,5-a]pyrimidine and 2-(4-bromophenyl)-5-methyl
      7,8-dihydro-6H-cyclopenta[g]pyrazolo[1,5-a]pyrimidine, and sheets of pi-stacked
      hydrogen-bonded chains in 2-(4-methoxyphenyl)-5-methyl-7,8-dihydro-6H
      cyclopenta[g]pyrazolo[1,5-a]pyrimidine.
AB  - 5-methyl-2-(4-methylphenyl)-7,8-dihydro-6H-cyclopenta[g]pyrazolo[1,5
      a]pyrimidine, C17H17N3, 2-(4-chlorophenyl)-5-methyl-7,8-dihydro-6H
      cyclopenta[g]pyrazolo[1,5-a]pyrimidine, C16H14ClN3, and 2-(4-bromophenyl)-5
      methyl-7,8-dihydro-6H-cyclopenta[g]pyrazolo[1,5-a]pyrimidine, C16H14BrN3, are
      isostructural; in each compound, the molecules are linked into chains by a single
      C-H...pi(arene) hydrogen bond. Molecules of 2-(4-methoxyphenyl)-5-methyl-7,8
      dihydro-6H-cyclopenta[g]pyrazolo[1,5-a]pyrimidine, C17H17N3O, are linked by a
      single C-H...N hydrogen bond into chains, which are themselves linked into sheets
      by a pi-pi stacking interaction.

PMID- 15997082
TI  - Thiamine tetraphenylborate monohydrate: a two-dimensional hydrogen-bonded network
      with (4,4)-topology.
AB  - The title compound, 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)
      4-methylthiazolium tetraphenylborate monohydrate, C12H17N4OS+.C24H20B-.H2O, is a
      salt in which the thiamine cations are linked by hydrogen bonds into a two
      dimensional network having (4,4)-topology. The stacked sheets form channels,
      which are occupied by the anions; the cations and anions are linked by C
      H...pi(arene) hydrogen bonds.

PMID- 15997083
TI  - N-acetyl-4-[(2-hydroxybenzylidene)amino]benzenesulfonamide monohydrate and N
      acetyl-4-[(5-bromo-2-hydroxybenzylidene)amino]benzenesulfonamide monohydrate.
AB  - Molecules of the title compounds, C15H14N2O4S.H2O and C15H13BrN2O4S.H2O, adopt an
      E configuration about the azomethine C=N double bond. In both molecules, the two
      benzene rings and the azomethine group are practically coplanar, as a result of
      intramolecular hydrogen bonds involving the hydroxy O atom and azomethine N atom.
      The angular disposition of the bonds about the S atom deviates significantly from
      that of a regular tetrahedron. In the crystal structures, both compounds form two
      dimensional layers parallel to the (100) plane.

PMID- 15997084
TI  - The proton-transfer compounds of strychnine with achiral salicylic acids:
      strychninium 3,5-dinitrosalicylate and the strychninium 5-nitrosalicylate bis(5
      nitrosalicylic acid) adduct.
AB  - In the crystal structures of the proton-transfer compounds of strychnine with 3,5
      dinitrosalicylic acid, namely strychninium 3,5-dinitrosalicylate,
      C21H23N2O2+.C7H3N2O7-, (I), and 5-nitrosalicylic acid, namely strychninium-5
      nitrosalicylate-5-nitrosalicylic acid (1/1/2), C21H23N2O2+.C7H4NO5-.2C7H5NO5,
      (II), protonation of one of the N atoms of the strychnine molecule occurs and
      this group is subsequently involved in intermolecular hydrogen-bonding
      interactions. In (I), this is four-centred, the primary being with an adjacent
      strychninium carbonyl O-atom acceptor in a side-to-side interaction giving linear
      chains. Other interactions are with the phenolate and nitro O-atom acceptors of
      the anionic species, resulting in a one-dimensional polymer structure. In (II),
      the N+-H interaction is three-centred, the hydrogen bonding involving carboxyl O
      atom acceptors of the anion and both acid adduct species, giving unique discrete
      hetero-tetramer units. The structure of (II) also features pi-bonding
      interactions between the two acid adduct molecules.

PMID- 15997085
TI  - Polymorphism in bipodal O,O'-dimethyl N,N'-(m
      phenylenedicarbonyl)bis(thiocarbamate).
AB  - The title compound, C12H12N2O4S2, crystallizes in white and yellow polymeric
      forms as a result of interesting anti-anti and syn-anti conformational isomerism
      of the thiocarbonyl and carbonyl moieties relative to one another. This work is
      the first reported X-ray crystallographic structure determination of isomers of
      this class of bipodal ligand. The white form, anti-anti, (I), crystallizes with
      the benzene ring lying about a twofold rotation axis, resulting in both of the
      thiocarbonyl and carbonyl moieties being anti relative to each other. The yellow
      modification crystallizes as syn-anti, (II), with one thiocarbonyl moiety syn and
      the other anti relative to the respective carbonyl groups. The individual
      molecules of both (I) and (II) are extensively linked through intermolecular
      hydrogen bonds. Intermolecular hydrogen bonding in (II) includes a network of
      bifurcated N-H...O and N-H...S hydrogen bonds, while molecules of (I) include
      bifurcated C-H...O hydrogen bonds.

PMID- 15997086
TI  - Evaluation of distribution patterns for copper and zinc in metallothionein and
      superoxide dismutase in chronic liver diseases and hepatocellular carcinoma using
      high-performance liquid chromatography (HPLC).
AB  - It has been reported that the copper (Cu) content of hepatocytes increases in
      chronic liver diseases and small hepatocellular carcinoma (HCC). In cells, Cu
      exists mainly as Cu-metallothionein (MT) or Cu, zinc (Zn)-superoxide dismutase
      (SOD). In this study, we investigated the biochemical state of Cu in the
      hepatocytes of patients with HCC using high-performance liquid chromatography
      (HPLC). The subjects of present study were 23 patients with HCC who underwent
      liver resection. The cancerous tissue and non-cancerous hepatic parenchyma with
      chronic disease were analyzed. In addition, as a normal control, hepatic tissue
      was collected at autopsy from 13 patients with no liver disease. Each sample was
      diluted with buffer, chilled, homogenized, and centrifuged. The supernatant was
      fractionated using HPLC. The metal contents of each fraction were measured using
      a desktop-type inductively coupled plasma (ICP) emission spectrochemical
      analyzer. HPLC analysis showed that MT existed mainly as Zn-MT in the normal
      hepatic tissue. The case of Cu,Zn-MT was significantly greater than Zn-MT in the
      non-cancerous, but diseased hepatic parenchyma than in the normal hepatic tissue
      (p<0.01). In comparison with non-cancerous hepatic parenchyma, the Cu-MT in the
      cancerous section was significantly greater than the Cu,Zn-MT (p<0.01). The Cu
      content for MT was significantly higher in small HCC (<40 mm) (p<0.01), and the
      absence of Cu or Zn in the MT fraction was significantly more frequent in the
      large HCC (>or=40 mm) (p<0.01). The Cu and Zn content for SOD in the samples
      showed no significant difference. Increase in the Cu content in the cancerous
      hepatic tissue were, thought to be reflecting changes in the distribution of Cu
      in the MT fraction of hepatic tissues.

PMID- 15997087
TI  - Correlation between ketone body level in selenium-deficient rats and oxidative
      damages.
AB  - The age dependence of ketone body levels (KBLs) and oxidative damages in selenium
      deficient (SeD) and normal rats were compared. The feeding SeD diets gave
      ketogenesis and higher KBLs especially in younger rats. However, KBLs in SeD rats
      seemed to decrease with their age. Feeding 0.1 mg/kg Se in water with SeD diet
      did not affect the KBLs in young (8 week old) rats, whereas the addition of Se
      reduced the KBLs in older (20 week old) rats. Blood KBLs showed some correlations
      with tissue damage. TBARSs showed no correlations with the tissue damages and
      KBLs when the values were compared between the same age, while better correlation
      was obtained between urinary KBLs of 6-20 week old normal rats and the liver
      TBARSs of 4-16 week old normal rats. The oxidative injury might induce liver
      damage with some delay. SeD rat kidney TBARS levels normalized by protein had
      some correlations with BUN and blood KBL. Kidney may be sensitive to the
      oxidative stresses and/or injuries. Tissue damages of SeD rats decreased with
      age. In contrast, oxidative injuries might be gradually accumulated in normal rat
      tissue. Oxidative stress can be visible by gradual accumulation of small damages
      during the aging, while large stress in young rats can be buffered and masked.
      The aging based accumulation of oxidative injuries might also be correlated with
      KBLs, while it might not give notable tissue damages.

PMID- 15997088
TI  - Identification of differentially expressed genes in hepatic HepG2 cells treated
      with acetaminophen using suppression subtractive hybridization.
AB  - Acetaminophen (APAP) is widely used for the treatment of pain and fever. Although
      it is safe at therapeutic doses, APAP is toxic at higher doses and can cause
      severe damage to the liver. To clarify the mechanism of APAP-related liver
      damage, we attempted the identification of the differential gene expression in
      response to APAP treatment in hepatic HepG2 cells. In the present study, we used
      the technique of suppression subtractive hybridization (SSH) for the
      identification of the differentially expressed genes between untreated and
      treated cells and identified 14 candidate genes showing increased expression in
      response to APAP treatment. RT-PCR and real-time RT-PCR analysis confirmed that
      the expression of two genes was increased within 24 h following APAP treatment.
      Among them, only lysyl hydroxylase 2 expression was increased in a time- and dose
      dependent manner. Furthermore, the expression of lysyl hydroxylase 2 was shown to
      be increased in the livers of APAP-treated mice compared to untreated controls.
      The increased expression of lysyl hydroxylase 2 was also observed when the cells
      were exposed to other hepatotoxins, ethanol and isoniazid. Since lysyl
      hydroxylase 2 is known to be a key enzyme of liver fibrosis, the increased
      expression of lysyl hydroxylase 2 may be involved in hepatotoxins-related liver
      fibrosis.

PMID- 15997089
TI  - Protective effect of puerariae radix on oxidative stress induced by hydrogen
      peroxide and streptozotocin.
AB  - This study evaluated the protective effect of Puerariae radix against the
      oxidative stress induced by hydrogen peroxide (H2O2) and streptozotocin in vitro
      and in vivo, respectively. The ethanol extract scavenged intracellular reactive
      oxygen species (ROS), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and
      prevented lipid peroxidation. This radical scavenging activity of the ethanol
      extract protected the cell viability of Chinese hamster lung fibroblast (V79-4)
      cells exposed to H2O2. Furthermore, this extract reduced the formation of
      apoptotic cells induced by H2O2, which was demonstrated by the decreased number
      of sub G(1) hypo-diploid cells and apoptotic cell body formation. The extract
      increased the activities of the cellular antioxidant enzymes, superoxide
      dismutase (SOD) and catalase (CAT). Administration of the extract to the
      streptozotocin induced diabetic rats decreased the blood glucose levels. The
      diabetic rats showed low activities of superoxide dismutase and catalase in the
      liver, and the ethanol extract increased the CAT activity. The increased level of
      lipid peroxidation in the diabetic rats reverted to near normal levels after
      being treated with the extract. This study showed that Puerariae radix was
      effective in the amelioration of diabetes, which may be a consequence of its
      antioxidant potential.

PMID- 15997090
TI  - The Role of dihydropyrazines in accelerated death of Escherichia coli on addition
      of copper(II).
AB  - Dihydropyrazines (DHPs), which are derived from sugars, inhibit the growth of
      Escherichia coli. Addition of copper(II) ion (Cu2+) accelerates the effect of
      DHPs, resulting in cell death. Investigation of the lethal effect in several DNA
      repair-deficient or detoxifying enzyme-deficient mutant strains and radical
      scavengers suggested that the cytotoxic and genotoxic damage was caused by
      radical species (hydroxyl, superoxide anion, and carbon-centered radicals)
      generated from reaction of DHPs with Cu2+.

PMID- 15997091
TI  - Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on
      doxorubicin-induced cardiotoxicity.
AB  - Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy.
      Many recent studies have shown that DOX toxicity involves generation of reactive
      oxygen species (ROS). Although protection or alleviation of DOX toxicity can be
      achieved by administration of antioxidant vitamins such as ascorbic acid and
      vitamin E, their cardioprotective effect remains controversial. Thus alternative
      naturally occurring antioxidants may potentially be candidates for antioxidant
      therapy. In this study, we investigated the antioxidative and cytoprotective
      effects of Phyllanthus urinaria (PU) against DOX toxicity using H9c2 cardiac
      myoblasts. The total antioxidant capacity of PU (1 mg/ml) was 5306.75+/-461.62
      FRAP value (microM). DOX IC50 values were used to evaluate the cytoprotective
      effects of PU ethanolic extract (1 or 10 microg/ml) in comparison with those of
      ascorbic acid (VIT C, 100 microM) and N-acetylcysteine (NAC, 100 microM). PU
      treatments (1 or 10 microg/ml) dose dependently caused rightward DOX IC50 shifts
      of 2.8- and 8.5-fold, respectively while treatments with VIT C and NAC increased
      DOX IC50 by 3.3- and 4.2-fold, respectively. Additionally, lipid peroxidation and
      caspase-3 activity were parameters used to evaluate cytoprotective effect. All
      antioxidants completely inhibited cellular lipid peroxidation and caspase-3
      activation induced by DOX (1 microM). Endogenous antioxidant defense such as
      total glutathione (tGSH), catalase and superoxide dismutase (SOD) activity was
      also modulated by the antioxidants. PU treatment alone dose dependently increased
      tGSH, and this effect was retained in the presence of DOX. Similar effect was
      observed in the assessment of catalase and SOD enzyme activity. The nuclear
      factor kappaB (NFkappaB) transcription factor assay demonstrated that all
      antioxidants significantly inhibited DOX-induced NFkappaB activation. Our results
      suggest that PU protection against DOX cardiotoxicity was mediated through
      multiple pathways and this plant may serve as an alternative source of
      antioxidants for prevention of DOX cardiotoxicity.

PMID- 15997092
TI  - Attenuation of hyperglycemia and hyperlipidemia in streptozotocin-induced
      diabetic rats by aqueous extract of seed of Tamarindus indica.
AB  - Streptozotocin (STZ)-induced diabetic rats were divided into mild diabetic (MD)
      and severe diabetic (SD) on the basis of fasting blood glucose (FBG) levels.
      Diabetes was confirmed here by intravenous glucose tolerance test (GTT),
      biochemical assay of glycogen content in liver and skeletal muscle, glucose-6
      phosphatase activity in liver, and serum insulin levels. Hyperlipidemia developed
      in these experimental diabetic rats was assessed by quantification of total
      cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density
      lipoprotein cholesterol (LDLc) and triglyceride (TG) in serum. Aqueous extract of
      seed of Tamarindus indica was given to MD and SD rats at the dose of 80 mg and
      120 mg/0.5 ml distilled water/100 g body weight/d respectively for 14 d.
      Significant attenuation of hyperglycemia was indicated by measuring FBG, glycogen
      level and glucose-6-phosphatase activity along with monitoring of intravenous GTT
      and serum insulin level. Similarly, correction of hyperlipidemia in diabetic rats
      after this extract supplementation was confirmed by significant reduction in the
      levels of above-mentioned hyperlipidemic indicators. Intravenous GTT was
      performed that highlights the antidiabetic action of this extract is not due to
      its effect on the intestinal rate of glucose absorption but may be due to
      modulation of intracellular glucose utilization in target organs. This study
      focus the efficacy of this extract for the management of experimental diabetes in
      rat model which may shed some light on the scientific basis of ancient herbal
      therapy in this line using this seed.

PMID- 15997093
TI  - The immunosuppressive effect of Gamisanghyulyunbueum through inhibition of
      mitogen-activated protein kinase and nuclear factor activation in MOLT-4 cells.
AB  - Gamisanghyulyunbueum (GSHYBE) has been used clinically to treat skin related
      disease in South Korea. We investigated GSHYBE-mediated changes in downstream T
      cell signal transduction. To determine the mechanism of inhibition, we have
      studied many of the major pathways in phytohemagglutinin (PHA)-activated T cell.
      We show that among the mitogen-activated protein kinase family activation of
      phosphorylation of extra cellular signal-regulated kinase 1/2 (ERK1/2, p44/42)
      and p38, but not c-jun NH2-terminal kinase is inhibited. In activated MOLT-4
      cells, the nuclear localization of nuclear factor of activated T cells (NFATc)
      was blocked by GSHYBE (1 mg/ml). Also, degradation of inhibitor kappaB-alpha and
      transactivation by nuclear factor-kappaB (NF-kappaB)/Rel A were impaired by
      GSHYBE (1 mg/ml). Furthermore, interlukin (IL)-2, IL-4 and Interferen (IFN)-gamma
      secretion by PHA activated MOLT-4 cells and peripheral blood mononuclear cells
      (PBMC) were significantly diminishes following GSHYBE treatment (1 mg/ml). Also,
      oral administration of GSHYBE inhibited IL-2 secretion in skin allergic reaction.
      In conclusion, our data indicate that GSHYBE treatment of T cells inhibits ERK1/2
      and p38 activation and nuclear translocation of NFATc, NF-kappaB, resulting in
      diminished secretion of IL-2.

PMID- 15997094
TI  - Effects of propolis on hypoxanthine-xanthine oxidase-induced toxicity in
      cultivated human cells and on neutrophil elastase activity.
AB  - The inhibition of the proliferation rate of the immortalized human cell line ECV
      304 after oxidant damage by oxygen radicals generated in a hypoxanthin-xanthine
      oxidase system and the protection provided by various propolis extracts was
      determined. Best inhibition was demonstrated by 60-80% ethanolic extracts (IC50
      of approximately 2 microg dry weight/ml) and by the ethyl acetate extract (IC50
      of 6.9 microg dry weight/ml). The beneficial effect of polar extracts was quite
      weak. Human neutrophil elastase activity was inhibited distinctively by ethanolic
      (60 to 96%) and ethyl acetate extracts (IC50 of approximately 2 microg dry
      weight/ml). Both activities seem to be responsible for the anti-inflammatory
      effect of the extract.

PMID- 15997095
TI  - Characterization of the pharmacology of YM-198313 on volume-regulated anion
      channels.
AB  - Activation of the volume-regulated anion channels (VRAC) is considered to be
      involved in arrhythmia, but it has not yet been fully elucidated because of the
      lack of its high affinitive and selective compounds. A newly synthesized
      compound, YM-198313 (sodium 4-({[2-(methylthio)benzyl]amino}-5-[(1
      phenylethyl)thio]isothiazol-3-olate), strongly inhibited VRAC in HeLa cells with
      an IC50 of 3.03+/-0.05 microM. However, YM-198313 weakly affected both the Ca2+
      activated Cl- channels in HTC cells and the cAMP-activated Cl- channels in T84
      cells, demonstrating that this compound is selective for VRAC among Cl- channels.
      At 10 microM, YM-198313 almost completely (100+/-7.8%) inhibited the VRAC current
      in guinea pig atrial myocytes. However, at the same concentration, YM-198313
      showed little inhibitory effect on the cardiac cation currents in ventricular
      myocytes. We believe that YM-198313 is a potent and selective VRAC inhibitor,
      therefore, it should be use to clarify the role VRAC plays in arrhythmia.

PMID- 15997096
TI  - A new retinoid-like compound that activates peroxisome proliferator-activated
      receptors and lowers blood glucose in diabetic mice.
AB  - Retinoid X receptor (RXR) forms heterodimers with peroxisome proliferator
      activated receptors (PPARs, with subtypes of alpha, delta and gamma), and the
      heterodimers can be activated by either an RXR or a PPAR subtype-specific ligand.
      Based on the chemical structure of the RXR natural ligand, 9-cis-retinoic acid (9
      cis-RA), we designed and synthesized a retinoid-like compound, CS018. In vitro
      characterizations by cell-based reporter gene assays indicated that CS018
      activated RXR homodimers and the heterodimers of RXR with PPARs, but not with
      farnesoid X-activated receptor (FXR) and liver X-activated receptor (LXR).
      Furthermore, RT-PCR results showed that CS018 induced the expression of the
      PPARgamma target genes, CD36 and lipoprotein lipase (LPL). In vivo studies on the
      diabetic db/db mice demonstrated that CS018 dramatically lowered the animal blood
      glucose levels. CS018 thus may represent a new retinoid-like compound that
      activates RXR/PPARs and has potential therapeutic applications in type 2 diabetes
      and other metabolic diseases.

PMID- 15997097
TI  - Transport mechanism for L-lactic acid in human myocytes using human prototypic
      embryonal rhabdomyosarcoma cell line (RD cells).
AB  - Monocarboxylate transporter (MCT), which cotransport L-lactic acid and protons
      across cell membranes, are important for regulation of muscle pH. However, it has
      not been demonstrated in detail whether MCT isoform contribute to the transport
      of L-lactic acid in skeletal muscle. The aim of this study was to characterize L
      lactic acid transport using an human rhabdomyosarcoma (RD) cell line as a model
      of human skeletal muscle. mRNAs of MCT 1, 2 and 4 were found to be expressed in
      RD cells. The [14C] L-lactic acid uptake was concentration-dependent with a Km of
      1.19 mM. This Km value was comparable to its Km values for MCT1 or MCT2. MCT1
      mRNA was found to be present markedly greater than that MCT2. Therefore, MCT1
      most probably acts on L-lactic acid uptake at RD cells. [14C] L-Lactic acid
      efflux in RD cells was inhibited by alpha-cyano-4-hydroxycinnamate (CHC) but not
      by butyric acid, a substrate of MCT1. Accordingly, MCT2 or MCT4 is responsible
      for L-lactic acid efflux by RD cells. MCT4 mRNA was found to be present
      significantly greater than that MCT2. We conclude that MCT1 is responsible for L
      lactic acid uptake and L-lactic acid efflux is mediated by MCT4 in RD cells.

PMID- 15997098
TI  - Differential cytotoxicity of anticancer agents in pre- and post-immortal
      lymphoblastoid cell lines.
AB  - We studied the cytotoxic effect of various anticancer agents on lymphoblastoid
      cell lines transformed by Epstein-Barr virus. Post-immortal N0005 (post-N0005) is
      an immortalized cell line derived from pre-immortal N0005 (pre-N0005) accompanied
      by increased telomerase activity, short-telomere, abnormal karyotypes, mutation
      of p53 gene, down regulation of p16/Rb and the ability to grow in soft agar
      medium. Compared with pre-N0005 cells, post-N0005 cells were significantly
      (p<0.001 by the Student t test) more resistant to the killing activity of seven
      DNA-modifying agents: camptothecin, etoposide, bleomycin, fluorouracil,
      thioguanine, melphalan and actinomycin D. However, both pre-N0005 and post-N0005
      cells showed similar levels of cytotoxicity against four DNA-non-modifying
      agents: colchicine, paclitaxel, vincristine and methotrexate. DNA-modifying and
      DNA-non-modifying agents are distinguished by their different sensitivities with
      pre-N0005 and post-N0005. Based on these results, we propose that pre-N0005 and
      post-N0005 cell lines be used as a new method to assess and screen anticancer
      agents.

PMID- 15997099
TI  - A red wine vinegar beverage can inhibit the renin-angiotensin system:
      experimental evidence in vivo.
AB  - A new beverage made of red wine vinegar and grape juice (Budo-no-megumi) was
      developed for people who wish to take effective amount of both polyphenols and
      vinegar. Since the beverage was recently demonstrated to exert hypotensive effect
      in rats, we analyzed its underlying mechanisms in this study. Sprague-Dawley rats
      were anesthetized with pentobarbital, and the blood pressure and lead II ECG were
      continuously monitored (n=6). The effects of recommended volume of the beverage
      (3 ml/kg, p.o.) on the renin-angiotensin system were assessed in vivo. At the
      basal control state, the increase in the mean blood pressure induced by the
      angiotensin I (1 microg/kg, i.v.) and norepinephrine (0.3-3 microg/kg, i.v.) were
      +57+/-2 and +36+/-8 mmHg, respectively. Sixty minutes after the administration of
      the beverage, the angiotensin I-induced pressor response decreased to +45+/-7
      mmHg at 60 min (p<0.05), whereas no significant change was detected in the
      norepinephrine-induced pressor response. In another parallel series of the
      experiment using Sprague-Dawley rats (n=6), the serum angiotensin-converting
      enzyme activity was 39.4+/-1.2 IU/l at basal control state, which was slightly
      but significantly decreased to 37.0+/-1.4 IU/l at 60 min after the administration
      of the beverage (p<0.01). These results suggest that previously described
      hypotensive action of the beverage may be partly induced by the inhibition of
      angiotensin-converting enzyme.

PMID- 15997100
TI  - Evaluation of polyphenolic acid esters as potential antioxidants.
AB  - Six polyphenolic acid esters were synthesized and their antioxidative properties
      were evaluated in three model systems [2,2'-diphenyl-1-picrylhydrazyl (DPPH) free
      radical scavenging assay, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)
      induced lipid peroxidation system, and the dye-bleaching assay of peroxynitrite
      radical]. Among these compounds, we found that compounds 4 [3,4-dihydroxy-benzoic
      acid-(2-phenoxyethyl ester)], and 5 [3,4-dihydroxy-cinnamic acid-(2-phenoxyethyl
      ester)] provided comparable activity to caffeic acid phenethyl ester (CAPE) in
      the DPPH model. Compound 3 [2,5-dihydroxy-benzoic acid-(2-phenoxyethyl ester)],
      was found to be more active than CAPE in the AAPH system, it also displayed about
      2-fold greater activity than CAPE in the peroxynitrite radical model. These
      results suggest that these phenolic acid ester derivatives, with their potent
      anti-oxidant activities, may have useful applications as antioxidants.

PMID- 15997101
TI  - Synthesis and anticonvulsant activity of 1-substituted-7-benzyloxy-4,5-dihydro
      [1,2,4]triazolo[4,3-a]quinoline.
AB  - Starting from 6-hydroxy-3,4-dihydro-1H-quinoline-2-one, a series of 1-substituted
      7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines was synthesized and
      their structures were characterized using IR, 1H-NMR, MS, and elemental analysis
      techniques. Anticonvulsant activity was evaluated in the maximal electroshock
      (MES) test, subcutaneous pentylenetetrazol (scMet) test, and rotarod
      neurotoxicity test. The most active compound was 7-benzyloxy-4,5-dihydro
      [1,2,4]triazolo[4,3-a]quinoline 4a. Its ED50 in the MES and scMet tests was 17.3
      and 24 mg.kg-1, respectively. The safest compound was 4 g, 1-phenyl-7-benzyloxy
      4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline, with TD50 and protective index (PI)
      (PI=TD50/ED50) values of greater than 300 mg.kg-1 and 13, respectively. The PI
      value of compound 4 g was better than that of most marketed drugs. Structure
      activity relationships are also described in this paper.

PMID- 15997102
TI  - Inhibition of human cytochrome P450 2E1 by halogenated anilines, phenols, and
      thiophenols.
AB  - A total of 44 variously halogenated derivatives of aniline, phenol, and
      thiophenol were subjected to analysis of their inhibitory effect on human
      cytochrome P450 (CYP) 2E1 to investigate the structure-activity relationships in
      halogenated phenyl derivatives. The activity of human CYP2E1 of the microsomes
      from baculovirus-transfected insect cells expressing recombinant human CYP2E1 was
      determined by measuring quinoline 3-hydroxylation, which was detectable by
      fluorescence monitoring (Ex=355 nm and Em=460 nm). Diethyldithiocarbamate (DDTC),
      a specific inhibitor of CYP2E1, potently inhibited quinoline 3-hydroxylation
      (IC50=8.9 microM). The effects of halogen-substitution in 32 aniline derivatives
      on the CYP2E1 inhibition can be summarized as follows: more enhancement by
      chlorine- and bromine-substitution than by fluorine-substitution, more
      enhancement by para- and metha-halogen-substitution than by ortho-halogen
      substitution, and more enhancement by dihalogen-substitution than by mono- and
      trihalogen-substitution except for trifluorine-substitution. The greatest
      enhancement of the inhibitory activity was observed in 3,4-dichloroaniline
      (IC50=8.0 microM) and 3,5-dichloroaniline (IC50=9.2 microM), and their inhibitory
      activities were very close to that of DDTC. All of the dichlorophenols and
      dichlorothiophenols were compared with dichloroanilines for CYP2E1 inhibition.
      Although dichlorothiophenols showed similar or more potent inhibitory activities
      than dichloroanilines, dichlorophenols showed less inhibitory activities. 3,4
      Dichlorothiophenol and 3,5-dichlorothiophenol showed very potent inhibition and
      their IC50 values were 5.3 and 5.2 microM, respectively. These results suggest
      that 3,4- and 3,5-dichlorophenyl derivatives may be useful as potent CYP2E1
      inhibitors.

PMID- 15997103
TI  - Antipyretic, analgesic and muscle relaxant activities of pueraria isoflavonoids
      and their metabolites from Pueraria lobata Ohwi-a traditional Chinese drug.
AB  - We evaluated the antipyretic, analgesic, and muscle relaxant activities of
      Pueraria isoflavonoids and their metabolites in mice. The glycosides daidzin and
      genistin significantly reduced fever induced by lipopolysaccharide (LPS). Their
      metabolites, daidzein and p-ethylphenol, also significantly reduced fever induced
      by LPS. In addition, daidzin, daidzein, dihydrodaidzein, and p-ethylphenol showed
      analgesic activity as assessed by the acetic acid-induced writhing test.
      Furthermore, equol and p-ethylphenol showed muscle relaxant activity in the
      rotarod and horizontal wire test. These results suggest that these compounds play
      a major role in the therapeutic activity of Pueraria isoflavonoids.

PMID- 15997104
TI  - Melanogenesis stimulation in murine b16 melanoma cells by umberiferae plant
      extracts and their coumarin constituents.
AB  - Melanogenesis stimulation activities of seven ethanolic extracts obtained from
      Umbelliferae plants used as Chinese crude drugs, namely the roots of Angelica
      dahurica BENTH. et HOOK., A. biserrata SHEN et YUAN, Notopterygium incisum TING,
      Heracleum lanatum MICHX., and H. candicans WALL., and the fruits of Cinidium
      monnieri (L.) CUSSON and C. formosanum YABE, were examined by using cultured
      murine B16 melanoma cells. Among them, the extract (5, 25 microg/ml) of H.
      lanatum showed a potent stimulatory effect on melanogenesis with significant
      enhancement of cell proliferation in a dose-dependent manner. The melanogenesis
      stimulatory effects of sixteen coumarins (1-16) isolated from the seven
      Umbelliferae crude drugs were also examined. Among them, linear-furocoumarins
      [psoralen (1), xanthotoxin (2), bergapten (3), and isopimpinellin (4)] and
      angular-furocoumarin [sphondin (13)] exhibited potent melanogenesis stimulation
      activity. From the view point of structure-activity relationships, it may be
      assumed that a linear-furocoumarin ring having a hydrogen and/or methoxyl group
      at 5 and 8 positions such as 1, 2, 3 and 4 was preferable for the melanogenesis
      stimulation activity. The introduction of a prenyl group into the furocoumarin
      ring was disadvantageous. Coumarin derivatives having a simple coumarin ring were
      inactive.

PMID- 15997105
TI  - Anti-inflammatory activities of aqueous extract from Radix Ophiopogon japonicus
      and its two constituents.
AB  - To provide some pharmacological evidence for its clinical use in inflammatory
      diseases, anti-inflammatory effect of the aqueous extract from Radix Ophiopogon
      japonicus (ROJ-ext), a traditional Chinese herb, was examined in mouse and rat
      models. ROJ-ext significantly inhibited xylene-induced ear swelling and
      carrageenan-induced paw edema in mice when given orally at doses of 25 and 50
      mg/kg. Moreover, ROJ-ext also remarkably suppressed carrageenan-induced pleural
      leukocyte migration in rats and zymosan A-evoked peritoneal total leukocyte and
      neutrophil migration in mice, while had no obvious effect on pleural
      prostaglandin E2 level. Furthermore, two active compounds were isolated from ROJ
      ext and identified as ruscogenin and ophiopogonin D. As the results, ROJ-ext,
      ruscogenin and ophiopogonin D dose-dependently reduced phorbol-12-myristate-13
      acetate (PMA)-induced adhesion of HL-60 cells to ECV304 cells, with IC50 of 42.85
      microg/ml, 7.76 nmol/l and 1.38 nmol/l, respectively. However, they showed no
      inhibitory effect on PMA-induced cyclooxygense-2 (COX-2) mRNA expression in
      ECV304 cells. Ruscogenin and ophiopogonin D also notably decreased zymosan A
      induced peritoneal leukocyte migration, in comparison with ROJ-ext. These results
      demonstrate that ROJ-ext presents remarkable anti-inflammatory activity and
      ruscogenin and ophiopogonin D are two of its active components, which supported
      its traditional use in the treatment of various diseases associated with
      inflammation.

PMID- 15997106
TI  - Effect of methanol extract of Sorbus cortex in a rat model of L-NAME-induced
      atherosclerosis.
AB  - Chronic inhibition of nitric oxide (NO) synthesis by administration of high dose
      of N(G)-nitro-L-arginine methylester (L-NAME) induces vascular inflammation and
      subsequent atherosclerosis. We aimed to investigate whether the methanol extract
      of Sorbus commixta cortex (MSC) is able to prevent inflammatory process in a rat
      model of L-NAME-induced atherosclerosis. Chronic treatment with low or high doses
      of MSC prevented the L-NAME-induced increase in monocyte chemoattractant protein
      1 (MCP-1) and nuclear factor-kappaB (NF-kappaB) p65 expressions as well as
      adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in aorta. In addition,
      increased endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) expressions
      and decreased endothelial cell NO synthase (ecNOS) expression in aorta from L
      NAME treated group was reversed by treatment with MSC. From the histological
      examination, aortic segment from the L-NAME-treated rats revealed a thickening of
      intima and media, which was ameliorated by treatment with MSC. In conclusion, our
      results indicate that MSC can prevent atherosclerosis by inhibiting vascular over
      expressions of vasoactive materials, pro-inflammatory transcription factor, and
      adhesion molecules and by augmenting ecNOS in chronic L-NAME-treated rat model.

PMID- 15997107
TI  - Protective effects of aucubin isolated from Eucommia ulmoides against UVB-induced
      oxidative stress in human skin fibroblasts.
AB  - Ultraviolet-B (UVB) irradiation has been demonstrated to produce reactive oxygen
      species (ROS) in the cells and skin, which induces the synthesis of matrix
      metalloproteinases (MMPs), causing skin photoaging. Using the human skin
      fibroblast HS68 cell line in the present study, we investigated the
      photoprotective effects of aucubin from Eucommia ulmoides. Pretreatment with
      aucubin significantly inhibited the production of MMP-1 by 57% when compared to
      the UVB-irradiated cells. Additionally, the senescence-associated beta
      galactosidase (SA beta-gal) activity was markedly decreased in the presence of
      aucubin, which indicates it as an antiphoto-induced aging compound. As the effect
      of aucubin was determined against ROS, the inhibited ROS formation and
      malondialdehyde (MDA) levels, and the increased cell viability and glutathione
      (GSH) level were observed with aucubin under UVB irradiation. Based upon these
      results, it was suggested that aucubin might play an important role in the
      cellular defense mechanism against UV radiation-induced photoaging. An
      understanding of the antioxidant properties of aucubin could, in part, act to
      elucidate its protective mechanism on the human skin photoaging.

PMID- 15997108
TI  - The effect of clodronate on the integrity and viability of rat small intestine in
      vitro-a comparison with EDTA.
AB  - Although substances, which can increase the paracellular permeability of
      intestinal mucosa, could be very helpful for increasing the bioavailability of
      hydrophilic drugs, they are not used therapeutically due to the possibilities of
      acute or long-term toxicity (intestinal inflammations due to penetration of
      bacterial fragments into subepithelial spaces). In this paper the abilities of a
      calcium chelator EDTA and clodronate (a first generation bisphosphonate) to
      increase the paracellular permeability were assessed using rat jejunum in side-by
      side diffusion chambers while the viability of the tissue was monitored by
      transepithelial potential difference. Although clodronate is less potent than
      EDTA in depleting calcium from the intestinal tissue, it significantly increased
      the paracellular permeability of viable rat jejunum "in vitro" when tested at 15
      mM and higher concentrations (the highest therapeutic dose dissolved in 250 ml
      gives a 22 mM solution of clodronate). This effect was reversible under "high
      calcium" conditions. Since clodronate therapy does not have any long-term
      consequences it was concluded that a safe, transient increase of small intestinal
      permeability is possible. However, the acute gastrointestinal undesired effects,
      which can develop during the therapy with high doses of clodronate, might also
      occur after oral applications of paracellular permeability enhancers. Namely, 30
      mM and higher concentrations of clodronate caused a loss of the tissue viability
      in all rat jejunal segments tested in "in vitro" conditions. A similar effect was
      observed with much lower concentrations of EDTA.

PMID- 15997109
TI  - Effect of nitric oxide on beta-glucan/indomethacin-induced septic shock.
AB  - We have previously shown that repeated administration of nonsteroidal anti
      inflammatory drugs (NSAIDs) to mice treated with beta-glucan, a biological
      response modifier, induced severe lethality. The lethality would be strongly
      related to the translocation of enterobacterial flora to the peritoneal cavity
      and disruption of the cytokine network. Reports suggest that nitric oxide (NO)
      can have an effective or detrimental role in septic shock. In the present study,
      we examined the effect of NO, an inflammatory mediator, on beta
      glucan/indomethacin (IND)- induced septic shock by inhibiting its synthesis with
      N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective NO synthase (NOS)
      inhibitor. Nitrite concentration was used as an indicator of NO generation.
      Mortality in beta-glucan/IND-treated mice was increased by administering L-NAME.
      Numbers of bacteria in various organs of mice treated with beta-glucan/IND rose
      significantly within a couple of days of the administration of L-NAME.
      Additionally, TNF-alpha, IL-1beta, and IL-6 concentrations were enhanced in
      peritoneal exuded cells in culture. These results suggest a significant loss of
      the bactericidal activity of macrophages on the administration of a NOS inhibitor
      which enhanced the rate of enterobacterial invasion to the peritoneal cavity,
      resulting in systemic inflammatory response syndrome. The production of NO,
      therefore, provides a protective effect in beta-glucan/IND-induced sepsis.

PMID- 15997110
TI  - Reducing the impact of binding of UCN-01 to human alpha1-acid glycoprotein by
      encapsulation in liposomes.
AB  - A liposomal formulation of UCN-01 was studied to prevent binding of drug to human
      alpha1-acid glycoprotein (hAGP). The release of drug from liposomes added to
      various media was investigated by monitoring the concentration of UCN-01 in
      different fractions. Protein bound UCN-01 was separated from liposomal UCN-01 and
      free UCN-01 by gel chromatography and the drug content in the fractions was
      measured by high-performance liquid chromatography. Also, the blood levels of
      hAGP bound drug and drug retained in liposomes were assessed after intravenous
      administration to rats of UCN-01 liposomes together with hAGP. In media
      containing hAGP, but not rat AGP, UCN-01 was released from liposomes. When UCN-01
      liposomes were mixed with rat plasma plus hAGP, the UCN-01 in the liposomes was
      only gradually released so that some drug remained in the liposomes, and
      therefore not bound to hAGP, for up to 24 h. After the mixture of liposomal UCN
      01 and hAGP was injected into rats, some UCN-01 was retained in liposomes for
      several hours. Encapsulation of UCN-01 into liposomes is an effective method of
      preventing binding of UCN-01 to hAGP.

PMID- 15997111
TI  - Soybean oil in total parenteral nutrition maintains albumin and antioxidant
      enzyme mRNA levels.
AB  - Changes in albumin and antioxidant enzyme mRNA expression in infant rat liver
      following administration of total parenteral nutrition (TPN) with/without soybean
      oil emulsion were studied. Infant rats were divided into three groups: group
      1=oral diet, group 2=TPN without fat, and group 3=TPN with 20% of calories from
      soybean oil emulsion. The period of TPN administration was 4 d. Serum aspartate
      aminotransferase and alanine aminotransferase levels were higher in group 2 than
      in the other groups, with similar levels seen in the other groups. Albumin, Cu,
      Zn-superoxide dismutase, and glutaredoxin 1 mRNA expression levels were lower in
      group 2 than in the other groups, with similar levels seen in the other groups.
      Catalase mRNA expression was higher in group 1 than in the other groups, with the
      lowest level seen in group 2. Soybean oil emulsion should be included in TPN
      regimens to prevent down-regulation of albumin and antioxidant enzyme mRNA
      expression.

PMID- 15997112
TI  - Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in
      rats fed a high-fat and high-cholesterol diet.
AB  - Bacillus polyfermenticus SCD, commonly referred to as Bispan strain, is used as a
      host in bioindustry and has been shown to have several human health benefits. In
      a recent in vitro study, we discovered that B. polyfermenticus SCD exerts
      cholesterol-lowering and antioxidant effects. Here, we evaluate the effects of B.
      polyfermenticus SCD on the lipid and antioxidant metabolisms of
      hypercholesterolemic rats. Twenty male Sprague-Dawley rats were divided into two
      groups after a 1-week adaptation period and were fed for 6 weeks on either a high
      fat-high cholesterol diet, or a high fat-high cholesterol diet supplemented with
      B. polyfermenticus SCD (3.1x10(6) cfu/d). B. polyfermenticus SCD significantly
      reduced plasma low-density-lipoprotein cholesterol, hepatic total cholesterol,
      and triglycerides, while increasing the fecal excretion rates of total
      cholesterol and triglycerides. In addition, B. polyfermenticus SCD might reduce
      the risk of atherosclerosis, as the ratio of high-density-lipoprotein cholesterol
      to total cholesterol was significantly higher than in the control group. B.
      polyfermenticus SCD led to an increase in total radical trapping antioxidant
      potential (TRAP) and a decrease in conjugated dienes in plasma. The erythrocytic
      glutathione peroxidase (GSH-Px) activity in the B. polyfermenticus group was
      significantly lower than that in the control group. Plasma TRAP levels exhibited
      a highly significant negative correlation with hepatic total cholesterol and a
      marginally significant negative correlation with total plasma cholesterol, while
      a significant positive correlation was detected between fecal total cholesterol
      and plasma TRAP. These results suggest that B. polyfermenticus SCD exerts
      significant health benefits through the modulation of physiologic functions
      including a variety of atherogenic lipid profiles and antioxidants in
      hypercholesterolemia.

PMID- 15997113
TI  - Bioactivation of morphine in human liver: isolation and identification of
      morphinone, a toxic metabolite.
AB  - Morphinone, identified in the bile of guinea pigs and rats given morphine, is a
      reactive electrophile and has the ability to bind to glutathione (GSH) and tissue
      macromolecules, leading to GSH depletion and cell damage. We previously
      demonstrated that the livers of various animal species are capable of forming
      morphinone from morphine. In this study, we examined whether the human liver can
      produce morphinone from morphine. HPLC analysis revealed that the incubation of
      morphine with the 9000xg supernatant of human liver in the presence of NAD(P) and
      2-mercaptoethanol (ME) gave a peak corresponding to the synthetic morphinone-ME
      adduct (MO-ME), which is readily formed by a nonenzymatic reaction of morphinone
      with ME. The reaction product was isolated and was unambiguously identified as MO
      ME using FAB-MS and NMR analyses in comparison with synthetic MO-ME. The
      conversion of morphine to morphinone required NAD(P), and NAD was a preferred
      cofactor over NADP. All the 9000xg supernatants from six human livers could
      produce morphinone at different rates, ranging from 30 to 120 nmol/g liver/30 min
      with NAD at pH 7.4. The enzyme activity responsible for the formation of
      morphinone from morphine was mainly localized in the microsomes. The microsomal
      enzyme activity was inhibited by steroids, lithocholic acid and indomethacin.
      Among these compounds, steroids with a 17beta-hydroxyl group almost completely
      depressed morphinone formation. In conclusion, the metabolic pathway of morphine
      to morphinone, a toxic metabolite, in human was shown for the first time in in
      vitro experiments.

PMID- 15997114
TI  - Similarity of acid proteinases secreted by Candida albicans NIH A-207 and NIH B
      792 strains cultured in BSA-supplemented medium.
AB  - Candida albicans NIH A-207 (serotype A) and NIH B-792 (serotype B) strains
      secreted one acid proteinases (AP) each in a yeast carbon-based medium
      supplemented with bovine serum albumin (BSA) as the sole nitrogen source.
      Isolation of AP from the culture filtrates was achieved by dialysis, followed by
      DEAE-Sepharose and Biogel P-100 column chromatographies. It was found that both
      enzymes from the two strains had very similar properties when examined. The
      molecular weights and isoelectric points were found to be 43 kDa and pH 4.0,
      respectively. The amino acid components and first 12 N-terminal amino acid
      sequences were virtually identical in both enzymes. The optimum pH of the enzymes
      was 3.5-4.0. The enzymes were heat-labile, and decreases in their activities were
      found above 37 degrees C. The AP activities were completely inhibited by the
      addition of pepstatin. No other inhibitor among those tested had any effect. The
      enzymes degraded all proteins examined, especially host defense factors such as
      immunoglobulin G and the granulocyte colony stimulating factor. The enzymes also
      caused similar degrees of enhancement of vascular permeability when they were
      injected into the dorsal skin of guinea pigs.

PMID- 15997115
TI  - Conventional HPLC method used for simultaneous determination of the seven HIV
      protease inhibitors and nonnucleoside reverse transcription inhibitor efavirenz
      in human plasma.
AB  - We developed a simple HPLC method for the simultaneous quantitative determination
      of seven HIV protease inhibitors: amprenavir (APV), atazanavir (ATV), indinavir
      (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and
      a nonnucleoside reverse transcription inhibitor, efavirenz (EFV). This method
      involves a rapid liquid-liquid drug extraction from plasma, the use of an
      isocratic elution on a reversed-phase C18 column, and an ultraviolet detection at
      a single wavelength (205 nm). The mobile phase consisted of 39% 50 mM phosphate
      buffer (pH 5.9), 22% methanol and 39% acetonitrile. Forty-eight samples could be
      measured in one day since the runtime of one sample is 30 min. The assay has been
      validated over a concentration range of 0.05 to 12.20 microg/ml for APV, 0.09 to
      12.05 microg/ml for ATV, 0.05 to 12.01 microg/ml for IDV, 0.12 to 12.36 microg/ml
      for LPV, 0.18 to 12.20 microg/ml for NFV, 0.12 to 12.33 microg/ml for RTV, 0.12
      to 12.06 microg/ml for SQV, and 0.05 to 12.17 microg/ml for EFV. Calibration
      curves were linear in the described concentration ranges. The average accuracy
      ranged from 97.2 to 106.8%. Both the interday and intraday coefficients of
      variation for all drugs tested were less than 8.5%. This method provides a
      simple, accurate, and precise method for the therapeutic drug monitoring of the
      seven protease inhibitors and EFV in clinical routine use.

PMID- 15997116
TI  - Dietary supplementation with n-3 polyunsaturated fatty acids attenuates the
      depression of food-motivated behavior during zymosan-induced peritonitis.
AB  - Peripheral inflammation is accompanied by neurobehavioral alterations such as
      depression of feeding, exploratory and sexual behaviors. Our previous
      investigation reported that dietary enrichment with n-3 polyunsaturated fatty
      acids (PUFA) attenuated the depression of food-motivated behavior and social
      exploration, but not endocrinological and metabolic disturbances in the mice with
      systemic inflammation induced by lipopolysaccharide (LPS). We here demonstrate
      that dietary n-3 PUFA also attenuate the reduction of food-motivated behavior
      during zymosan-induced peritonitis in mice without influencing plasma leakage
      into peritoneum and writhing response. Our results suggest that the common
      mechanism is involved in the attenuation of behavioral depression during systemic
      and local inflammation by dietary n-3 PUFA.

PMID- 15997117
TI  - Inactivation of Vibrio vulnificus hemolysin by oligomerization but not
      proteolysis.
AB  - Vibrio vulnificus extracellular protease (VvpE) is believed to destroy its
      hemolysin (VvhA) in the late growth phase, without obvious experimental evidence.
      So, we attempted to elucidate the mechanism. The hemolytic activity steeply
      increased with the expression of the VvhA in the early growth phase, and then
      abruptly declined with the expression of VvpE in the late growth phase. However,
      the VvhA activity also abruptly declined in a VvpE-deficient mutant. In Western
      blot, the degradation of VvhA was not observed; instead, the oligomerization of
      VvhA increased with the concomitant loss of hemolytic activity. These results
      evidently indicate that the inactivation of VvhA is due to the novel
      oligomerization of VvhA by unknown mechanism, but not to the destruction of VvhA
      by VvpE, so that the routine functional assay measuring hemolytic activity cannot
      reflect the actual production of VvhA.

PMID- 15997118
TI  - Comparison of the inhibitory effects of docosahexaenoic acid (DHA) on U46619- and
      phenylephrine-induced contractions in guinea-pig aorta.
AB  - Inhibitory effects of docosahexaenoic acid (DHA) on the muscle contractions
      induced by U46619, a thromboxane A2 (TXA2) mimetic, and phenylephrine were
      compared in guinea-pig aorta. In de-endothelialized guinea-pig aortic ring
      preparations, DHA at 10 microM strongly inhibited a sustained contraction
      produced by U46619 (3-100 nM) whereas it did not exhibit an appreciable effect on
      phenylephrine (3-10 microM)-induced contraction. The present findings indicate
      that DHA inhibits more selectively TXA2 receptor (TP receptor)-mediated vascular
      contraction than alpha-adrenoceptor-mediated response. Selective inhibition by
      DHA of TP receptor-mediated contraction of blood vessels seems underlie in part
      the mechanisms by which this polyunsaturated fatty acid exerts its circulatory
      protective effects.

PMID- 15997119
TI  - Effects of dehydroepiandrosterone (DHEA) on ubiquinone and catalase in the livers
      of male F-344 rats.
AB  - The adrenal steroid, dehydroepiandrosterone (DHEA) acts as a peroxisome
      proliferator in the rodents. The present study examined the effects on cellular
      antioxidants ubiquinone and catalase in the liver of DHEA-treated rats. When
      administered to male F-344 rats for 8 weeks, DHEA produced a significant increase
      in hepatic ubiquinone-9 and lipid peroxide levels while no change was observed
      after 2 weeks. Activity of catalase, in contrast, followed an inverse pattern,
      being significantly induced at 2 weeks with a return to normal levels after 8
      weeks. A marked reduction of ubiquinone-10 in DHEA-treated rat livers was only
      observed after 2 weeks. These findings indicate the potentials of high dose DHEA
      to modulate ubiquinone in rat hepatic tissue.

PMID- 15997120
TI  - Reversal of fibrogenic events in liver by Emblica officinalis (fruit), an Indian
      natural drug.
AB  - A hydroalcoholic (50%) extract of Emblica officinalis (fruit) (EO-50) reduced the
      severity of hepatic fibrosis induced by carbon tetrachloride (CCl4) and
      thioacetamide (TAA). Improved liver function was observed by measuring the levels
      of aspartate aminotransaminase (AST), alanine aminotransferase (ALT), alkaline
      phosphatase (ALP) and bilirubin in serum. Hepatic parameters monitored were the
      levels of glutathione (GSH), lipid peroxidation (LPO) and hydroxyproline and the
      activities of catalase, glutathione peroxidase (GPx), Na+,K+-ATPase and
      cytochrome P450 (CYP 450 2E1) (aniline hydroxylation). The results suggested that
      EO-50 effectively reversed profibrogenic events possibly due to its promising
      antioxidative activity.

PMID- 15997121
TI  - Effects of erythromycin on plasma gastrin, somatostatin, and motilin levels in
      healthy volunteers and postoperative cancer patients.
AB  - Erythromycin, an antibiotic agent, is known to be a motilin receptor agonist.
      Motilin is a peptide hormone that regulates gastric motility. One of the
      gastrointestinal motility regulatory factors has been assumed to be the induction
      of changes in the levels of peptides (gastrin, somatostatin and motilin) in
      plasma. We have elucidated the effects of erythromycin by examining changes in
      the plasma levels of gastroinitestinal peptides. In this study, we investigated
      the effects of erythromycin on the plasma levels of gastrointestinal peptides
      (somatostatin, motilin, and gastrin) in healthy volunteers and patients with
      delayed gastric emptying (DGE). After a single oral administration, erythromycin
      caused a significant increase in plasma gastrin-like immunoreactive substance
      (IS) levels at 60 min. But the agent did not alter the levels of somatostatin-
      and motilin-IS. DGE is the most frequent postoperative complication after pylorus
      preserving pancreatoduodenectomy. Molitin is assumed to be one important factor
      that influences DGE. We also examined the effects of erythromycin on the plasma
      motilin-IS levels of postoperative patients. The plasma motilin-IS levels were
      increased after 1 week of oral administration of erythromycin compared with
      preadministration. These results suggest that the pharmacologic effects of
      erythromycin in promoting gastric emptying are closely related to changes in
      plasma motilin-IS levels.

PMID- 15997122
TI  - Anti-inflammatory activity of a new sphingosine derivative and cembrenoid
      diterpene (lobohedleolide) isolated from marine soft corals of Sinularia crassa
      TIXIER-DURIVAULT and Lobophytum species of the Andaman and Nicobar Islands.
AB  - The aim of this study is to determine the anti-inflammatory activity of a new
      sphingosine derivative (1) and cembrenoid diterpene (lobohedleolide) (2) isolated
      from the soft corals of Sinularia crassa and Lobophytum species respectively,
      collected on the coasts of Andaman and Nicobar Islands. The anti-inflammatory
      activity was evaluated using carrageenin-induced rat hind paw edema model for
      acute inflammation and cotton pellet granuloma model for chronic inflammation.
      Indomethacin was used as a standard drug in this study. Both the sphingosine
      derivative (1) and the cembrenoid diterpene (2) produced the maximum effect at a
      dose of 10 mg/kg and this is comparable to that of indomethacin (2 mg/kg,
      p<0.001). The observed anti-inflammatory activity is almost identical in both the
      types of experimental inflammation.

PMID- 15997123
TI  - Trypanocidal constituents in plants 5. Evaluation of some Mexican plants for
      their trypanocidal activity and active constituents in the seeds of Persea
      americana.
AB  - Crude extracts of Mexican medicinal plants were screened for trypanocidal
      activity against Trypanosoma cruzi, which is the etiological agent for Chagas'
      disease, one of the most serious protozoan diseases in Latin America. There were
      71 kinds of methanolic and other organic extracts from 65 plants, which were
      newly examined by a preliminary screening test to observe immobilization of
      epimastigotes and trypomastigotes of T. cruzi in vitro. The MeOH extract of seeds
      of Persea americana (avocado) showed moderate activity against epimastigotes. In
      order to identify the principal compounds for the activity, the MeOH extract was
      subjected to bioassay-guided fractionation. From the active fractions, six 1,2,4
      trihydroxyheptadecane derivatives and two 1,2,4-trihydroxynonadecane derivatives
      including a new one were isolated. These compounds showed moderate activity
      against epimastigotes and trypomastigotes.

PMID- 15997124
TI  - Leakage of potassium from red blood cells following gamma ray irradiation in the
      presence of dipyridamole, trolox, human plasma or mannitol.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is a fatal
      complication of blood transfusion resulting from the contamination of blood
      products by leukocytes. In order to prevent this disease, gamma or X-ray
      irradiation of blood components,which can inactivate leukocytes, is currently
      used. However, the minimal doses needed to destroy lymphocytes promote the
      leakage of potassium from red blood cells (RBCs), which can induce other side
      effects, such as hyperpotassemia and cardiac arrest. The reactive oxygen species
      (ROS) generated by the irradiation of aqueous solutions may accelerate the
      leakage through oxidation of the RBC membrane. Here we studied the effect of
      dipyridamole, Trolox, human plasma or mannitol on the leakage of potassium from
      RBCs following irradiation. RBC preparations (hematocrit; 30%) containing
      antioxidants were irradiated at 30 Gy and stored at 4 degrees C for 7 d. The
      leakage of potassium from the RBCs caused by the irradiation was significantly
      suppressed by dipyridamole (more than 50 microM), Trolox (more than 5 mM) or
      human plasma (50%). Mannitol (80 mM) is used to inhibit hemolysis as a
      constituent of MAP solution, which is a solution used for the storage of RBC
      products in Japan. Here it was clarified that the leakage of potassium from not
      only irradiated but also non-irradiated RBCs was unexpectedly promoted by
      mannitol. The amount of mannitol in MAP solution may have to be reconsidered. The
      osmotic pressure of the RBC preparation increased in a manner dependent on the
      concentration of mannitol. The elevated osmotic pressure may promote the leakage.
      In conclusion, although antioxidants have the potential to suppress the leakage
      of potassium ascribed to the irradiation, the extent of the suppression (10-20%)
      by dipyridamole (DPM), Trolox or human plasma seems insufficient for the clinical
      use of these agents as an additive for MAP solution.

PMID- 15997125
TI  - Self-assembled complexes of non-cross-linked amphiphilic polymeric ligands with
      inorganic species: highly active and reusable solid-phase polymeric catalysts.
AB  - I present herein the development of highly active and reusable polymeric
      catalysts produced by self-assembly process of non-cross-linked amphiphilic
      polymeric ligands with inorganic species. Thus, PWAA 1 prepared from H3PW12O40
      and poly[(N-isopropylacrylamide)-co-(acrylamide with ammonium salt)] is suitable
      for oxidation of alcohols, amines, and sulfides in aqueous hydrogen peroxide.
      PdAS 2 produced by self-organization of (NH4)2PdCl4 and poly[(N
      isopropylacrylamide)10-co-diphenylphosphinostyrene] is an excellent recyclable
      catalyst for Suzuki-Miyaura reaction in water, water-organic solvent, and organic
      solvent. It is commercially available from Tokyo Kasei Kogyo (TCI). PdAS-V 3
      assembled from (NH4)2PdCl4 and poly[(N-isopropylacrylamide)5-co
      diphenylphosphinostyrene] provides recycling system of itself for Mizorogi-Heck
      reaction. TiSS 4 made from Ti(O-i-Pr)4 and poly(styryl-linked binaphtholate-co
      styrene) promotes an enantioselective carbonyl-ene reaction as a recyclable
      catalyst.

PMID- 15997126
TI  - Isolation and structure determination of bioactive isoflavones from callus
      culture of Dipteryx odorata.
AB  - Crude extracts of callus and roots of Dipteryx odorata were analyzed by HPLC to
      detect and quantify isoflavone contents. Based on spectroscopic and X-ray
      crystallography data the structures of two isoflavones were elucidated as 7
      hydroxy-4',6-dimethoxyisoflavone and 3',7-dihydroxy-4',6-dimethoxyisoflavone. The
      production of dry biomass of 7-hydroxy-4',6-dimethoxyisoflavone in cultured
      callus was 4.12 mg/g, approximately eleven fold higher than the amount
      accumulated in roots of D. odorata wild-growing plants. The 7-hydroxy-4',6
      dimethoxyisoflavone was effective against glyceraldehyde-3-phosphate
      dehydrogenase from Trypanosoma cruzi. This is the first report on those bioactive
      isoflavones accumulated in callus of D. odorata.

PMID- 15997127
TI  - Synthetic studies on d-biotin, part 9. An improved asymmetric synthetic route to
      d-biotin via Hoffmann-Roche lactone-thiolactone approach.
AB  - An efficient and highly stereoselective total synthesis of d-biotin has been
      achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2)
      with an overall yield of 33%. Polymer-supported oxazaborolidine-catalyzed
      asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in
      introducing stereogenic centers into the d-biotin molecule.

PMID- 15997128
TI  - Potent inhibitory effects of N-aryl S-alkylthiocarbamate derivatives on the dopa
      oxidase activity of mushroom tyrosinase.
AB  - This study reports the potent inhibitory effect of N-aryl S-alkylthiocarbamate
      derivatives on mushroom tyrosinase (MT) activity. N-Aryl S-alkylthiocarbamate
      derivatives were found to exhibit a potent inhibitory effect on the dopa (3,4
      dihydroxyphenylalanine) oxidase activity of mushroom tyrosinase. Most of the N
      aryl S-alkylthiocarbamate derivatives (compounds from A to J) exhibited higher
      inhibitory effects than kojic acid (IC50=318 microM), a well known tyrosinase
      inhibitor. Tyrosinase was the most inhibited by S-phenetyl N-phenylthiocarbamate
      (compound E, IC50=7.25 microM), and this inhibition was 44 times stronger than
      that of kojic acid. Compound E exhibited 95.0% of inhibition at 100 microM. A
      kinetic study of MT inhibition by compound E using the Lineweaver-Burk plots
      analysis was performed. And the kinetics profiles observed suggest that compound
      E competitively inhibits MT.

PMID- 15997129
TI  - Improvement of fluorescence characteristics of coumarins: syntheses and
      fluorescence properties of 6-methoxycoumarin and benzocoumarin derivatives as
      novel fluorophores emitting in the longer wavelength region and their application
      to analytical reagents.
AB  - To improve the fluorescence characteristics, especially emission wavelength, of
      coumarins, various 3-substituted-6-methoxycoumarin derivatives were synthesized,
      and then benzocoumarin derivatives were also synthesized in expectation of the
      shift to the longer wavelength region by the extension of the conjugated system.
      Their fluorescence properties were investigated spectrophotometrically in
      acetonitrile and evaluated from the viewpoint of the intramolecular charge
      transfer (ICT) between push- and pull-substituents in the ground and the excited
      states. Among them, benzocoumarin derivatives especially fluoresced in the longer
      wavelength around 540 nm with remarkably large Stokes shifts beyond 10,000 cm(
      1). Using such fluorophores, some novel fluorescence derivatization reagents for
      carboxylic acids, alcohols, phenols, and amines were preliminarily prepared as an
      example, and their derivatized products were also found to fluoresce in the
      longer wavelength region with large Stokes shifts.

PMID- 15997130
TI  - Evaluation of the compaction properties of a solid dispersion of indomethacin
      with crospovidone by tableting process analyzer.
AB  - A powder solid dispersion system (SD) of indomethacin (IM) with crospovidone
      (CrosPVP) possesses good fluidity and can be used for tablet formulation. Tablets
      of SD can be prepared by direct compression and have adequate hardness and a
      small variation in weight. Forces during the tableting process were measured with
      a tableting process analyzer (TabAll) equipped with a single-punch. The pressure
      transmission ratio (PTR) from the upper to the lower punch and the die wall force
      (DWF) were examined during the tableting process. Ejection force (EF) and scraper
      pressure (SP) were measured for determining the capping and sticking properties
      during the tableting process. Adding 1% magnesium stearate (MS) to the SD
      resulted in high PTR and DWF values and a low EF value. PTR and DWF values
      increased and EF value decreased when MS and microcrystalline cellulose (MCC)
      were added to the SD. A thousand tablets could be manufactured without problems
      such as sticking or capping when 1% MS and 50% MCC were added to the SD
      containing 25% IM.

PMID- 15997131
TI  - Preparation of highly potent and selective non-peptide antagonists of the
      arginine vasopressin V1A receptor by introduction of a 2-ethyl-1H-1-imidazolyl
      group.
AB  - To find a new series of arginine vasopressin (AVP) V1A receptor antagonists, the
      influence of the 2-phenyl group of 2-phenyl-4'-[(2,3,4,5-tetrahydro-1H-1
      benzazepin-1-yl)carbonyl]benzanilide (7) was investigated. Replacement of the 2
      phenyl group by a 2-ethyl-1H-imidazol-1-yl group was effective in yielding a V1A
      selective compound. Moreover, this imidazolyl group was introduced in the same
      position in YM-35471 (6), and further studies of these compounds were performed.
      Consequently, we found that the (Z)-4'-({4,4-difluoro-5-[(N
      cyclopropylcarbamoyl)methylene]-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl}carbonyl)
      2-(2-ethyl-1H-1-imidazol-1-yl)benzanilide (9f) exhibited highly potent affinity
      and selectivity, and was the most potent antagonist for the V1A receptor among
      our compounds. The synthesis and pharmacological evaluation of these compounds
      are described in this paper.

PMID- 15997132
TI  - Microwave drying of granules containing a moisture-sensitive drug: a promising
      alternative to fluid bed and hot air oven drying.
AB  - The impact of microwave drying and binders (copolyvidone and povidone) on the
      degradation of acetylsalicylic acid (ASA) and physical properties of granules
      were compared with conventional drying methods. Moist granules containing ASA
      were prepared using a high shear granulator and dried with hot air oven, fluid
      bed or microwave (static or dynamic bed) dryers. Percent ASA degradation, size
      and size distribution, friability and flow properties of the granules were
      determined. Granules dried with the dynamic bed microwave dryer showed the least
      amount of ASA degradation, followed by fluid bed dryer, static bed microwave oven
      and hot air oven. The use of microwave drying with a static granular bed
      adversely affected ASA degradation and drying capability. Dynamic bed microwave
      dryer had the highest drying capability followed by fluid bed, static bed
      microwave dryer and conventional hot air oven. The intensity of microwave did not
      affect ASA degradation, size distribution, friability and flow properties of the
      granules. Mixing/agitating of granules during drying affected the granular
      physical properties studied. Copolyvidone resulted in lower amount of granular
      residual moisture content and ASA degradation on storage than povidone,
      especially for static bed microwave drying. In conclusion, microwave drying
      technology has been shown to be a promising alternative for drying granules
      containing a moisture-sensitive drug.

PMID- 15997133
TI  - Antimitotic and antifungal C-3/C-3''-biflavanones from Stellera chamaejasme.
AB  - Two new C-3/C-3'' biflavanones, chamaejasmenin D (1) and isochamaejasmenin B (2),
      were isolated from the roots of Stellera chamaejasme, together with five known
      biflavanones, chamaejasmenin A (3), chamaejasmenin B (4), neochamaejasmin A (5),
      sikokianin A (6), and chamaejasmenin C (7). Their structures were elucidated by
      spectroscopic methods, including 2D NMR techniques. Among these compounds, 1-3
      demonstrated potent antimitotic and antifungal activity with minimum inhibitory
      concentration (MIC) values of 6.25, 6.25, and 3.12 microg/ml, respectively.

PMID- 15997134
TI  - Selective enhancement of scopadulcic acid B production in the cultured tissues of
      Scoparia dulcis by methyl jasmonate.
AB  - The effects of methyl jasmonate (MeJA) on isoprenoid production were evaluated in
      cultured tissues of Scoparia dulcis. It was found that MeJA suppressed the
      accumulation of chlorophylls, carotenoids, phytol and beta-sitosterol in the
      tissues. MeJA, however, remarkably enhanced the production of scopadulcic acid B
      (SDB), with 10 microM being optimal observed concentration for stimulation of SDB
      production. The maximum concentration of SDB was observed 6 d after MeJA
      treatment.

PMID- 15997135
TI  - A monoterpene glucoside and three megastigmane glycosides from Juniperus communis
      var. depressa.
AB  - A new monoterpene glucoside (1) and three new natural megastigmane glycosides (2
      4) were isolated along with a known megastigmane glucoside (5) from twigs with
      leaves of Juniperus communis var. depressa (Cupressaceae) collected in Oregon,
      U.S.A., and their structures were determined on the basis of spectral and
      chemical evidence. In addition, the antibacterial activities of the isolated
      components against Helicobacter pylori were also investigated.

PMID- 15997136
TI  - Constituents of Holothuroidea, 15. Isolation of ante-iso type regio-isomer on
      long chain base moiety of glucocerebroside from the sea cucumber Holothuria
      leucospilota.
AB  - An ante-iso type regio-isomer on the long chain base moiety of a
      glucocerebroside, HLC-2-A, has been isolated from its parent glucocerebroside
      molecular species HLC-2 composed of iso and ante-iso isomers, from the less polar
      lipid fraction of a chloroform/methanol extract of the sea cucumber Holothuria
      leucospilota. Reverse-phase HPLC that included a recycling system was effective
      in separating the regio-isomer from its counterpart, revealing a very close
      resemblance in structure. Other typical glucocerebroside molecular species HLC-1
      and HLC-3 were obtained together with HLC-2. The structures of these
      glucocerebrosides were determined on the basis of chemical and spectroscopic
      evidence.

PMID- 15997137
TI  - Intermolecular hydrogen bonding of steroid compounds: PFG NMR diffusion study,
      cold-spray ionization (CSI)-MS and X-ray analysis.
AB  - An extensive analysis of hydrogen bonding of steroid compounds in diluted
      solution is preformed by pulsed field gradient (PFG) NMR and cold-spray
      ionization (CSI)-MS, in the solid state by X-ray crystallographic analysis. The
      formation of hydrogen bond interaction are quantified and discussed. Although X
      ray analysis in the crystalline state and CSI-MS measurement in solution
      suggested that the observed diffusion coefficient D(obs) of the steroid compounds
      may vary in accordance with the number of hydrogen bonds, the actual observed
      D(obs) value determined from the diffusion studies diminished constantly without
      correlation on the decreasing numbers of hydrogen bonds. Comparison of two
      different calibration profiles of calculated molecular volume (V(cal)) vs.
      D(obs), which are obtained from compounds possessing no hydrogen bonding and the
      steroid compounds, formation of a chain structure (cluster) based on
      intermolecular hydrogen bonding of the steroid compounds is unambiguously
      confirmed.

PMID- 15997138
TI  - Presence of peroxyradicals in cigarette smoke and the scavenging effect of
      shikonin, a naphthoquinone pigment.
AB  - Using a new method having been developed for the purpose of quantitative
      determination for peroxyradicals, the presence of peroxyradicals was proved in
      cigarette smoke. In brief, peroxyradicals in cigarette smoke were measured by ESR
      spectrometry coupled to non-reductive scavenging of 1,1-diphenyl-2-picrylhydrazyl
      (DPPH). As a result, peroxyradicals were found to be major reactive oxygen
      species (ROS) since the concentration of peroxyradicals recovered from cigarette
      smoke was much higher than that of any of other ROS (superoxide and hydroxyl
      radical) and nitric oxide. Furthermore, several antioxidants (ascorbic acid,
      reduced glutathione, epigallocatechin gallate, shikonin) were examined for
      scavenging activity against peroxyradicals in the cigarette smoke. Among them
      shikonin alone exerted the scavenging activity, suggesting that shikonin is
      promising antioxidant for cigarette filters because of its effectiveness against
      broad range of ROS including peroxyradicals, heat resistance, nonvolatility and
      high affinity to the filter.

PMID- 15997139
TI  - Staphylionosides A-K: megastigmane glucosides from the leaves of Staphylea
      bumalda DC.
AB  - Chemical investigation of leaves of Staphylea bumalda DC., collected in the
      suburbs of Hiroshima City, afforded 11 new megastigmane glucosides, named
      staphylionosides A-K (3-13), along with two known megastigmane glucosides (1, 2).
      The relative structures were elucidated from spectroscopic evidence, and the
      absolute structures of the aglycones were determined by means of the combination
      of beta-D-glucosylation-induced shift-trends and the modified Mosher's method.

PMID- 15997141
TI  - Evaluation of titanium dioxide as a pharmaceutical excipient for preformulation
      of a photo-labile drug: effect of physicochemical properties on the
      photostability of solid-state nisoldipine.
AB  - To characterize the photocatalytic activity of TiO2 via solid-state reaction, the
      relationship between the physicochemical properties and photocatalytic activity
      of TiO2 was investigated and estimated from the results of photodegradation of
      nisoldipine. The photodegradation of nisoldipine was significantly enhanced by
      addition of TiO2. Two degradation products, nitroso-phenylpyridine derivative and
      nitro-phenylpyridine derivative, were formed. The degree of photocatalytic
      activity of TiO2 was quite different between the various types of TiO2
      investigated, even when the crystalline phase was the same. As a result of the
      investigations into the relationship between the photocatalytic activity and
      physicochemical properties of TiO2, it was found that for the rutile form the
      photocatalytic activity has good correlation with specific surface area of TiO2,
      but poor correlation with water loss on drying of TiO2. However, for the anatase
      form, the photocatalytic activity has good correlation with water loss on drying
      of TiO2, but poor correlation with specific surface area. Moreover, it was found
      that the crystallinity of TiO2 has a moderate correlation with the photocatalytic
      activity of both crystal forms of TiO2. These results suggest that a degree of
      photocatalytic activity of TiO2 depends on the various physicochemical properties
      of each type of TiO2 investigated.

PMID- 15997140
TI  - New bicyclic taxane diterpenoids from Taxus sumatrana.
AB  - Investigation of an acetone extract of the leaves and twigs of Taxus sumatrana
      has resulted in the isolation of two new bicyclic taxoids, tasumatrols M (1), and
      N (2) and a new baccatin III derivative, tasumatrol O (3) together with the
      previous known 7-deacetylcanadensene (4) and 2alpha,7beta,13alpha-triacetoxy
      5alpha,9alpha-dihydroxy-2(3-->20) abeotaxa-4(20),11-dien-10-one. The structures
      of these taxanes were established on the basis of spectroscopic analyses,
      especially 1- and 2D NMR, and chemical derivatization.

PMID- 15997142
TI  - Biotransformation of ferulic acid into two new dihydrotrimers by Momordica
      charantia peroxidase.
AB  - As a result of a continuing investigation of the biotransformation of ferulic
      acid with H2O2/Momordica charantia peroxidase at pH 5.0 in the presence of
      acetone, triFA1 (1) and triFA2 (2), two new FA dehydrotrimers, have been
      isolated. The structures were elucidated from the spectroscopic data including 2D
      NMR such as HSQC, HMBC and NOESY data. TriFA1 (1) is a unique FA dehydrotrimer
      possessing a 3a,9b-dihydro-1H-furo[3,4-c][1]benzopyran-3(4H)-one ring system. The
      possible mechanism for the formation of triFA1 was also discussed.

PMID- 15997143
TI  - Ab initio molecular orbital study of the reactivity of active alkyl groups. VI.
      Modified reaction model for the elimination process of nitrosation reaction.
AB  - The mechanisms of nitrosation of acetone through sodium enolate [CH3COCH2]- Na+
      (1) or naked enolate [CH3COCH2]- (2) with tert-butyl nitrite (CH3)3CONO (3) were
      studied using ab initio molecular orbital (MO) methods. When the modified complex
      model was used in the elimination process, our results demonstrated the
      predominant formation of E-1-hydroxy-imino-2-oxo-propane CH3COCH=NOH (4E), in
      which a counter-cation of the base catalyst did not participate during the
      reaction. On the other hand, participation of the counter-cation during the
      reaction contributed to the formation of the Z-isomer of 4 (4Z).

PMID- 15997144
TI  - New polyoxygenated cyclohexenes from Uvaria kweichowensis and their antitumour
      activities.
AB  - Two new polyoxygenated cyclohexenes, kweichowenol A and B, were isolated from the
      leaves of Uvaria kweichowensis, and their structures were established on the
      basis of their spectral data. The two new compounds showed some antitumour
      activity by MTT assay.

PMID- 15997145
TI  - Humulene derivatives from Zingiber zerumbet with the inhibitory effects on
      lipopolysaccharide-induced nitric oxide production.
AB  - A new humulene sesquiterpene, 5-hydroxyzerumbone (5-hydroxy-2E,6E,9E-humulatrien
      8-one) (1) and a known compound, zerumboneoxide (2) were isolated from the
      rhizomes of Zingiber zerumbet (Zingiberaceae), and found to inhibit
      lipopolysaccharide-induced nitric oxide production in murine macrophage RAW 264.7
      cells with IC50 values of 14.1 and 23.5 microM, respectively, by bioassay-guided
      fractionation (positive control: N(omega)-monomethyl-L-arginine, IC50=21.3
      microM). The structure of 1 was determined by spectroscopic methods including 1D
      and 2D-NMR.

PMID- 15997146
TI  - Piperine from the fruits of Piper longum with inhibitory effect on monoamine
      oxidase and antidepressant-like activity.
AB  - A bioassay-guided isolation of the ethanol extract from the fruits of Piper
      longum yielded a known piperidine alkaloid, piperine, as a monoamine oxidase
      (MAO) inhibitor. Piperine showed an inhibitory effect against MAO-A (IC50 value:
      20.9 microM) and MAO-B (IC50 value: 7.0 microM). Kinetic analyses by a Lineweaver
      Burk plot clearly indicated that piperine competitively inhibited MAO-A and MAO-B
      with Ki values of 19.0+/-0.9 microM and 3.19+/-0.5 microM, respectively. The
      inhibition by piperine was found to be reversible by dialysis of the incubation
      mixture. In addition, the immobility times in the tail suspension test were
      significantly reduced by piperine, similar to that of the reference
      antidepressant fluoxetine, without accompanying changes in ambulation when
      assessed in an open-field. These results suggest that piperine possesses potent
      antidepressant-like properties that are mediated in part through the inhibition
      of MAO activity, and therefore represent a promising pharmacotherapeutic
      candidate as an antidepressant agent.

PMID- 15997147
TI  - A new phytoecdysteroid from Ajuga taiwanensis.
AB  - A new phytoecdysteroid, namely ajugalide-E (1), together with twenty five known
      compounds were isolated from Ajuga taiwanensis collected from Tainan, Taiwan.
      Their structures were determined by spectral analysis including high resolution
      one- and two-dimensional NMR spectroscopy.

PMID- 15997148
TI  - Tomato new sapogenols, isoesculeogenin A and esculeogenin B.
AB  - Two novel sapogenols, isoesculeogenin A (1) and esculeogenin B (2) of steroidal
      alkaloid glycosides, lycoperoside F and esculeoside B, respectively, isolated
      from the ripe tomato have been characterized as (5alpha,22R,23R,25S)-3beta,23,27
      trihydroxyspirosolane and (5alpha,22S,23R,25S)-22,26-epimino-16beta,23-epoxy
      3beta,23,27-trihydroxycholestane, respectively.

PMID- 15997149
TI  - Two new sesquiterpene lactones with the sulfonic acid group from Saussurea lappa.
AB  - Two new sesquiterpene lactones with the unusual sulfonic acid group, 13-sulfo
      dihydrosantamarine (1) and 13-sulfo-dihydroreynosin (2), have been isolated from
      the roots of Saussurea lappa C. Their structures, including the absolute
      configurations, were elucidated by spectroscopic methods.

PMID- 15997150
TI  - Synthesis and triplex-forming ability of 2',4'-BNAs bearing imidazoles as a
      nucleobase.
AB  - To expand the sequence of double-stranded DNA (dsDNA) targets in a triplex
      formation, 2',4'-BNAs (2'-O,4'-C-methylene bridged nucleic acids) having
      imidazoles as a nucleobase were synthesized and incorporated into
      oligonucleotides. Triplex-forming ability of the modified oligonucleotides was
      evaluated by using melting temperature (Tm) measurements.

PMID- 15997151
TI  - The isolation and structure elucidation of minor isoflavonoids from licorice of
      Glycyrrhiza glabra origin.
AB  - Two new isoflavanone and one new 3-arylcoumarin derivatives, along with a known
      compound 3,4-didehydroglabridin, were isolated from commercially available
      licorice of Glycyrrhiza glabra origin, and their structures were elucidated on
      the basis of both the chemical and spectroscopic evidence.

PMID- 15997152
TI  - Antibacterial caged-tetraprenylated xanthones from the fruits of Garcinia
      hanburyi.
AB  - A new caged-tetraprenylated xanthone, hanburinone (1), was isolated from the
      fresh fruits of Garcinia hanburyi together with four known caged-tetraprenylated
      xanthones; isomoreollin B (2), morellin (3), moreollic acid (4) and morellic acid
      (5). Their structures were elucidated by analysis of spectroscopic data and
      comparison of the NMR data with those reported previously. Compounds 4 and 5
      showed moderately antibacterial activity against methicillin-resistant
      Staphylococcus aureus with a MIC value of 25 microg/ml.

PMID- 15997153
TI  - Chemical constituents from roots of Taraxacum formosanum.
AB  - Two new compounds, taraxafolide (1) and (+)-taraxafolin-B (2) together with
      eighteen known compounds, which include one sesquiterpene, thirteen benzenoids,
      two indole alkaloids, one pyridine derivative and steroid mixtures were isolated
      and characterized from the fresh roots of Taraxacum formosanum. Structures of new
      compounds were determined by spectral analysis. (+)-Taraxafolin-B had the
      bioactive caffeic acid moiety, but its activity was weaker than alpha-tocopherol
      in DPPH radicals scavenging activity assay.

PMID- 15997154
TI  - Determination of patchoulic alcohol in Herba Pogostemonis by GC-MS-MS.
AB  - Patchoulic oil, the volatile oil of Pogostemon cablin (Blanco) Benth. and the
      Chinese crude drug Herba Pogostemonis, is widely used in the cosmetic and oral
      hygiene industries. Patchoulic alcohol is commonly used as an indicator for the
      quality assessment of dried P. cablin. However, the complexity of the herbal
      constituents makes it difficult for using conventional gas chromatography (GC)
      for analytical purpose. The present study established an accurate, sensitive and
      reproducible method for the quality assessment of the dried patchouli herb based
      on patchoulic alcohol content. A gas chromatography-tandem mass spectrometry
      (GC/MS/MS) method has been successfully developed and demonstrated for the
      determination of patchoulic alcohol content in the samples of dried P. cablin.
      The developed method was found to be convenient and facile in particular to
      tackle the complicated matrix problems always encountered in the herbs which
      contain high level of essential oils.

PMID- 15997155
TI  - A new highly oxygenated pseudoguaianolide from a collection of the flowers of
      Parthenium hysterophorus.
AB  - A new highly oxygenated pseudoguaianolide, 8-beta-acetoxyhysterone C, along with
      the known compounds, parthenin, coronopilin and hysterone C, has been isolated
      from a collection of the flowers of Parthenium hysterophorus. The structure of
      the new compound was derived from the extensive studies of its spectral (mainly
      1D and 2D NMR) data.

PMID- 15997156
TI  - Synthesis of DNA conjugate by mechanochemical solid-state polymerization and its
      affinity separation of oligonucleotides having single-base difference by
      capillary electrophoresis.
AB  - In this communication, we discuss the characterization of DNA conjugate
      synthesized by mechanochemical polymerization, Con-M, on the separation of model
      oligo-DNA and its single nucleotide polymorphisms (SNPs) by affinity capillary
      electrophoresis, compared with that prepared by radical-initiated solution
      polymerization, Con-RL. The average molecular weight of Con-M was similar to that
      of Con-RL, although the molecular weight distribution of Con-M was narrower than
      that of Con-RL. Capillary electrophoresis of oligo-DNA was performed using the
      capillary filled with DNA conjugate. The resolution of the capillary filled with
      Con-M was apparently higher than with Con-RL. It is considered that higher
      resolution using the capillary filled with Con-M could be ascribed not only to
      the narrow molecular weight distribution but also to the difference of copolymer
      structure.

PMID- 15997157
TI  - Biooxidation of (+)-catechin and (-)-epicatechin into 3,4-dihydroxyflavan
      derivatives by the endophytic fungus Diaporthe sp. isolated from a tea plant.
AB  - The microbial transformation of (+)-catechin (1) and (-)-epicatechin (2) by
      endophytic fungi isolated from a tea plant was investigated. It was found that
      the endophytic filamentous fungus Diaporthe sp. transformed them (1, 2) into the
      3,4-cis-dihydroxyflavan derivatives, (+)-(2R,3S,4S)-3,4,5,7,3',4'
      hexahydroxyflavan (3) and (-)-(2R,3R,4R)-3,4,5,7,3',4'-hexahydroxyflavan (7),
      respectively, whereas (-)-catechin (ent-1) and (+)-epicatechin (ent-2) with a 2S
      phenyl group resisted the biooxidation.

PMID- 15997158
TI  - Concise synthesis of dl-febrifugine.
AB  - Racemic compound (1) of the antimalarial agents febrifugine (d-1) was synthesized
      using an stereoselective Michael reaction of an omega-amidoenone (5) which was
      prepared by the Wittig reaction of piperidinediol (7).

PMID- 15997159
TI  - [Two regulatory mechanisms of histamine H1 receptor expression and their clinical
      significance].

PMID- 15997160
TI  - [Agonist-mediated internalization of histamine H1 receptors and changes in the
      drug sensitivity].

PMID- 15997161
TI  - [The role of mast cells in allergic inflammation--from the view point of innate
      immune system involvement].

PMID- 15997162
TI  - [The role of eosinophils in allergic inflammation].

PMID- 15997163
TI  - [Pharmacological analyses of mechanisms underlying nasal blockage using a guinea
      pig model of allergic rhinitis].

PMID- 15997164
TI  - [Social requirement of the antihistamines for Japanese pollinosis].

PMID- 15997165
TI  - [Molecular mechanism of vascular dysfunction in the insulin-resistant state].

PMID- 15997166
TI  - [The pharmacokinetics of oral antifungal drugs and their efficacy against
      cutaneous mycosis].

PMID- 15997167
TI  - [The front line of the treatment of anxiety disorders].

PMID- 15997168
TI  - [A hereditary postprandial hypertriglyceridemic (PHT) rabbit model].

PMID- 15997169
TI  - [Pharmacological and clinical profile of tiotropium bromide (Spiriva), a new long
      acting anticholinergic bronchodilator for COPD treatment].

PMID- 15997170
TI  - Forced exercise-induced flushing of tail skin in ovariectomized mice, as a new
      experimental model of menopausal hot flushes.
AB  - Hot flushes are the most common complaint of menopausal women. In the present
      study, a new animal model of hot flushes was established. Tail skin temperature
      was measured with a thermo tracer after mice were subjected to a forced exercise
      task using a motor driven treadmill. In ovariectomized mice, forced exercise for
      10 min was most effective in increasing tail skin temperature over that of sham
      operated mice. This elevation was blocked by estradiol replacement (1 mg/kg per
      week for 3 weeks), suggesting that our model simulates menopausal hot flushes.

PMID- 15997171
TI  - Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium
      after myocardial infarction.
AB  - Osteopontin has been reported to have an important role in cardiac fibrosis.
      However, little is known about the effects of angiotensin-converting enzyme
      inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin
      expression in infarcted myocardium. The purpose of this study was to elucidate
      the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac
      function as assessed by Doppler echocardiography and cardiac osteopontin
      expression associated with cardiac remodeling in myocardial infarcted rats. ACEI
      or ARB was administered after myocardial infarction (MI). At 4 weeks after MI,
      cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and
      ARB equally prevented left ventricular dilatation, reduction of ejection
      fraction, and the increase in E/A wave velocity ratio and the rate of E wave
      deceleration by MI. ACEI and ARB significantly suppressed increased mRNA
      expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin,
      and collagen I and III in the non-infarcted ventricle at 4 weeks.
      Immunohistochemically stained osteopontin was increased in interstitial fibrosis
      of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac
      fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits
      osteopontin expression in non-infarcted myocardium and prevents cardiac
      remodeling after MI.

PMID- 15997172
TI  - The effect of herbal medicine Toki-shakuyaku-san on blood pressure in an Nomega
      nitro-L-arginine methyl ester-induced pre-eclampsia rat model during pregnancy
      and the postpartum period.
AB  - The chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L
      arginine methyl ester (L-NAME) in pregnant rats induces a pre-eclampsia-like
      syndrome, including hypertension. We have previously reported the beneficial
      effects of Toki-shakuyaku-san (TS) in this model. In the present study we
      demonstrated the anti-hypertensive effect of TS in pre-eclampsia produced by
      prolonged L-NAME-infusion during the postpartum period. Analysis of blood sex
      steroids suggested that the level of progesterone differs between the TS
      effective (gestational day 19 and postpartum day 7) and TS-ineffective
      (postpartum day 1) periods. Co-administration of TS and progesterone inhibited L
      NAME-induced hypertension on postpartum day 1. Furthermore, the anti-hypertensive
      effect of TS on postpartum day 6 disappeared in the presence of a co-administered
      progesterone antagonist mifepristone. These data suggest that a certain level of
      progesterone may be an indispensable prerequisite for an anti-hypertensive effect
      of TS. Finally, the effects of TS are apparently unrelated to blood levels of NO,
      calcitonin gene-related peptide, and endothelin-1, which have been reported to
      modulate systolic blood pressure in the L-NAME-induced pre-eclampsia model. Thus,
      the use of TS may provide a new therapeutic strategy for pre-eclampsia, although
      elucidation of the mechanism of action of TS would be necessary to optimize
      treatment protocols.

PMID- 15997173
TI  - [Involvement of semaphorins in immunoregulation].
AB  - Semaphorins were identified originally as guidance cues for developing neuronal
      axons. However, it is becoming clear that several semaphorins play important
      roles in the immune system. For instance, Sema4D (CD100) enhances activation of B
      cells and dendritic cells through its receptor, CD72. Sema4A is crucially
      involved not only in T cell priming but also in Th1/Th2 regulation. Additional
      semaphorins and related molecules also have distinct biological activities in the
      immune system. We here review the current topic of immunoregulatory semaphorins
      which could be targets for potenciation of, and intervention for immune response.

PMID- 15997174
TI  - [The significance of anti-nuclear envelope (gp210) antibody in primary biliary
      cirrhosis].
AB  - Primary biliary cirrhosis (PBC) is considered to be an autoimmune disease
      selectively targeted for interlobular bile ducts. While anti-mitochondrial
      antibodies are specifically detected in more than 90% of PBC patients, anti
      nuclear envelope-gp210 antibodies are also specifically detected in 20-30% of PBC
      patients. In this review, we present 1, T cells specific for mitochondrial major
      epitope, PDC-E2 163-176, cross-react with peptides derived from nuclear envelope
      gp210 protein, 2, PBC patients who have sustained high antibody titers to gp210
      are at high risk for the progression to end-stage hepatic failure. These
      evidences may be very important for the epitope spreading of autoantigens from
      PDC-E2 to nuclear antigens and for the identification of target antigens on
      biliary epithelial cells which are recognized by cytotoxic T cells in PBC.

PMID- 15997175
TI  - [Specificities and clinical significance of autoantibodies directed against
      histones].
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      occurrence of numerous autoantibodies directed against nuclear antigens. Anti
      histone antibodies (AHA) are as prevalent as their anti-dsDNA counterparts in
      SLE. Despite their frequency and potential importance, there have not been given
      much attention to AHA until recently. Nucleosomes, the fundamental repeating
      units of the chromatin, are formed of complexes of histones and DNA. The
      nucleosome core particle is composed of a central tetramer of 2 molecules each of
      H3 and H4 flanked by 2 dimers of H2A and H2B and surrounded by 2 superhelical
      turns of approximately 146 base pairs of DNA. The full nucleosome contains a
      molecule of H1 located at the point where DNA enters and exits the nucleosome.
      Recent studies have shown that the post transcriptional modification of histone
      changes chromatin structure to regulate transcription and the concept of this
      mechanism "epigenetics" has become center of attention in the field of basic cell
      biology. There have been described diverging specificities of AHA. Many attempts
      to locate antigenic determinants recognized by AHA have been made and H1 and H2B
      have been thought as common targets in lupus patients. Studies on murine models
      of lupus have shown several interesting findings. The universal epitope is
      located on H2B in (NZBxNZW)F1 mice. In addition to core histones, MRL-MP/Fas(lpr)
      mice develop high titers of autoantibodies to H1. Autoimmunity to chromatin
      regularly involves humoral immune responses directed against H1. These histones
      appear to be an early (possibly initial trigger) autoantigen for this autoimmune
      response in lupus.

PMID- 15997176
TI  - [Fractalkine and inflammatory diseases].
AB  - The migration of leukocytes into inflamed peripheral tissues and lymphoid organs
      involves a cascade of molecular events finely regulated by cell adhesion
      molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that
      functions not only as a chemoattractant but also as an adhesion molecule, and is
      expressed on endothelial cells activated by proinflammatory cytokines. The
      fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes
      including NK cells and cytotoxic effector T cells (T(CE)), mature
      monocytes/macrophages, and mucosal dendritic cells, all of which play important
      roles in elimination of pathogens and cancer cells. Recently, accumulating
      evidence in both clinical studies and animal disease models has shown that
      fractalkine is also involved in the pathogenesis of various chronic inflammatory
      diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews
      the unique functions of fractalkine and its pathophysiological roles in various
      clinical conditions.

PMID- 15997177
TI  - [Molecular pathogenesis of Wiskott-Aldrich syndrome].
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused
      by mutations in the gene encoding the WAS protein (WASP). WASP is predominantly
      expressed in hematopoietic cells and regulates the reorganization of the actin
      cytoskeleton in response to various important cell stimuli including T cell
      receptor signaling. WASP is localized at the immunological synapses between T
      cells and antigen presenting cells, NK cells and target cells. Here we focus on
      recent basic and clinical research advances for WAS, which has given great
      insight into the relevance of WASP, its related molecules and its interacting
      proteins to basic cell biology, actin cytoskeleton, immunological defects and
      prediction of clinical outcome in WAS patients. In particular, we have reported
      the significance of WIP (WASP-interacting protein) for molecular regulation of
      WASP. In addition, we discuss recent basic approaches to gene therapy for WAS.

PMID- 15997178
TI  - [A case of interstitial pneumonia associated with dermatomyositis effectively
      treated with cyclosporin-A and cyclophosphamide pulse].
AB  - A 46-year-old male demonstrated edematous fingers on both hands in November 2003,
      and interstitial pneumonia was noted on chest X-ray during a medical check-up in
      December 2003. Since muscular weakness and fever developed thereafter, and
      interstitial pneumonia was aggravated on chest X-ray and CT, the patient was
      admitted to our hospital on March 25, 2004. Heliotrope-like erythema, and
      Gottron's sign were noted. Laboratory findings showed the following ; LDH 876 U/l
      ; CK 224 U/l ; CRP 5.68 mg/dl ; and KL-6 3270 U/ml. Autoantibodies such as anti
      Jo-1 antibody were all negative. Chest X-ray and CT showed ground-glass opacity
      in the bilateral lower dorsal regions of the lung, and reduced volume of the
      inferior lobe. He was diagnosed as having dermatomyositis (DM) associated with
      progressive interstitial pneumonia. Although a combination of steroid pulse
      therapy and Cyclosporin-A were administered, the pulmonary lesions became
      aggravated. Additional intravenous Cyclophosphamide (IVCY) was initiated on the
      6th hospital day, and interstitial pneumonia was markedly improved. Cases of
      progressive interstitial pneumonia associated with DM that are negative for anti
      Jo-1 antibody and show a low ratio of CK/LDH are resistant to various treatments.
      Our case suggested that combination therapy with steroid, Cyclosporin-A, and IVCY
      is useful for the treatment of progressive interstitial pneumonia with DM.

PMID- 15997179
TI  - [A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis,
      in that the histology of liver biopsy specimen was useful for diagnosis].
AB  - A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted
      to our hospital because of cholestasis and elevation of liver enzymes for 2
      months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC
      (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA,
      hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth
      muscle antibody. The histology of her liver biopsy specimen revealed interface
      hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for
      EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis.
      She was treated firstly with methylprednisolone pulses, then will prednisolone
      p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced
      because of her abnormal immune pathology. All abnormal laboratory parameters
      improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC
      became negative after 4 months. The histology of liver biopsy specimen was useful
      for the diagnosis of AIH in such a difficult case needed to be differentiated
      from EBV hepatitis.

PMID- 15997180
TI  - Microvasculature of the retina, ciliary processes and choroid in the North
      American raccoon (Procyon lotor) eye: a scanning electron microscopic study of
      corrosion casts.
AB  - We have studied the vasculature of the retina, ciliary processes and choroid in
      the North American raccoon (Procyon lotor), a nocturnal mammal, using light and
      scanning electron microscopic examination of corrosion casts. We carried out an
      identical study in the crab-eating macaque (Macaca fascicularis), which forages
      only during the daytime, in order to compare the ocular vasculature with that of
      nocturnal mammals. Our observations in raccoons demonstrated a photoreceptor
      layer associated with rich lymph and a poorly vascularized retina. The meridian
      region of the eye, which lies in the horizontal plane and pass around the optic
      disc, had a markedly sparse capillary network. This horizontal sparse vascular
      band may correspond to a visual streak. Ciliary process capillaries were
      delicate, and formed a well-developed and compact network. Choriocapillaries were
      quite thin and formed a coarse capillary network. This contrasted with the dense
      retinal and well-extended choroidal capillary networks noted in the macaques. Our
      findings suggest that the sparse retinal capillary network in raccoons is
      extremely beneficial for photon capture, thereby allowing the raccoon to see well
      at night, as the retinal vessels restrict the inflow of photons toward the
      photoreceptors. The well-developed lymph probably compensates for the sparse
      retinal capillaries and choriocapillaries and nourishes the retina in the
      nocturnal raccoon.

PMID- 15997181
TI  - Genomic diversity among equine herpesvirus-4 field isolates.
AB  - Infection with equine herpesvirus-4 (EHV-4) is a major cause of respiratory tract
      disease, equine rhinopneumonitis, in horses. Although the full sequence of EHV-4
      has been reported, genomic differences among EHV-4 field isolates have not yet
      been characterized. In this study, the genomic diversity between 23 Japanese EHV
      4 isolates was analyzed by digestion with restriction endonucleases (BamHI,
      BgIII, EcoRI, SacI, and SalI) and polymerase chain reaction (PCR). The
      restriction endonuclease digestion patterns of the EHV-4 field isolates showed
      distinct differences which included mobility shifts of some fragments as well as
      loss and/or gain of fragments. Two EHV-4 genes containing repeat sequences, ORFs
      24 and 71, were amplified by PCR and the amplified fragments were compared among
      the field isolates. The sizes of the amplified fragments varied among
      epizootiologically unrelated isolates, while the fragments of related isolates
      had the same size. The observed genomic diversity among EHV-4 field isolates may
      be a useful tool for epidemiological study of equine rhinopneumonitis by EHV-4
      infection.

PMID- 15997182
TI  - Genetic profile and serosurvey for virus infections of Japanese wild boars in
      Shikoku Island.
AB  - To estimate the genetic background of Japanese wild boars inhibiting the 4
      prefectures of Shikoku Island (Kagawa, Tokushima, Kouchi and Ehime), we examined
      haplotypes of mitochondrial DNA (mtDNA) and genotypes of the nuclear
      glucosephosphate isomerase-processed pseudogene (GPIP) in 189 wild boars. Of the
      8 different mtDNA haplotypes (J5, J10, J12, J13, J15, J19, J20 and E33) detected
      in Shikoku Island, the first to be identified were J19 and J20 (of Japanese wild
      boar lineage) and E33 (of European domestic pig lineage). The presence of
      haplotype E33 indicates local crossbreeding between wild boar and escaped
      domestic pigs and/or crossbred Inobuta. Four kinds of the GPIP genotypes were
      detected from 189 wild baors in Shikoku Island, but no European GPIP alleles were
      found. In 113 wild boars, no antibodies against Classical Swine Fever or
      Aujeszky's disease were detected, suggesting that they had not been exposed to
      those pathogens.

PMID- 15997183
TI  - The minimum infusion rate (MIR) of propofol for total intravenous anesthesia
      after premedication with xylazine in horses.
AB  - To investigate an adequate infusion rate of propofol for total intravenous
      anesthesia (TIVA) in horses, the minimum infusion rate (MIR) comparable to the
      minimum alveolar anesthetic concentration (MAC) of inhalation anesthetic was
      determined under constant ventilation condition by intermittent positive pressure
      ventilation (IPPV). In addition, arterial propofol concentration was measured to
      determine the concentration corresponding to the MIR (concentration preventing
      reaction to stimulus in 50% of population, Cp(50)). Further, 95% effective dose
      (ED(95)) was estimated as infusion rate for acquiring adequate anesthetic depth.
      Anesthetic depth was judged by the gross purposeful movement response to painful
      stimulus. MIR and Cp(50) were 0.10 +/- 0.02 mg/kg/min and 5.3 +/- 1.4 microg/ml,
      respectively. ED(95) was estimated as 0.14 mg/kg/min (1.4MIR).

PMID- 15997184
TI  - Effect of monoenergetic neutron irradiation on the postnatal development of the
      cochlea in C3H/HeN mice.
AB  - To investigate the toxic effect of neutrons at energies of approximately 1MeV on
      the ear, we exposed 7-day-old mice to 1.0 Gy of monoenergetic neutrons (1.026
      MeV) or (137)Cs gamma rays, and assessed subsequent morphological changes in the
      inner ear by light and scanning electron microscopy. Monoenergetic neutrons, but
      not gamma rays, caused acute changes in the ear. The epithelium of the greater
      epithelial ridge in the organ of Corti had disappeared by 72 hr post-irradiation,
      as a result of epithelial apoptosis observed 6 hr post-irradiation. Radiation
      could induce apoptotic cell death of the epithelium of the greater epithelial
      ridge at 3 or 4 days of age. Protruding structures were detected on the surface
      of the hair cells by 72 hr post-irradiation. The neutron-irradiation also caused
      the apoptotic cell death of epithelial cells at the nasal conchae, and subsequent
      acute otitis media continued until 10 weeks of age.

PMID- 15997185
TI  - Apolipoprotein gene polymorphisms as cause of cholesterol QTLs in mice.
AB  - Quantitative trait locus (QTL) analyses of plasma cholesterol levels were carried
      out in three sets of F(2) mice that were formed in a 'round-robin' manner from
      C57BL/6J, KK (-A(y)), and RR strains. Six QTLs were identified on chromosomes 1
      (Cq1, Cq2, and Cq6), 3 (Cq3), and 9 (Cq4 and Cq5); of these, Cq2 colocalized with
      Cq6, and Cq4 colocalized with Cq5. The major candidate gene for Cq2 and Cq6 is
      Apoa2, and that for Cq4 and Cq5 is Apoa4. The adequacy of polymorphisms in
      candidate genes as cause of QTLs was investigated in this study. For Apoa2, three
      different alleles (Apoa2(a), Apoa2(b), and Apoa2(c)) are known. Since there was
      no significant physiologic difference between Apoa2(a) and Apoa2(c) alleles,
      previous hypothesis that Apoa2(b) was different from Apoa2(a) and Apoa2(c) in the
      ability to increase cholesterol levels was further supported. Presumably, G-to-A
      substitution at nucleotide 84 and/or C-to-T substitution at nucleotide 182 are
      crucial to make the Apoa2(b) unique. On the other hand, for Apoa4, the most
      striking polymorphism was the number of Glu-Gln-Ala/Val-Gln repeats in carboxyl
      end; however, this might not be responsible for QTLs. Instead, a silent mutation,
      C-to-T substitution at nucleotide 771, was shown to be completely correlated with
      the occurrence of QTLs in a total of six F(2) intercrosses. Provisionally, but
      reasonably, these base substitutions are qualified as primary causes that
      constitute QTL effect. The potential strategy for identifying genes and base
      substitutions underlying QTLs is discussed.

PMID- 15997186
TI  - Effects of sugar cane extract on the modulation of immunity in pigs.
AB  - The experiment was aimed to test the efficacy of sugar cane extract (SCE) on the
      modulation of pig immunity under field conditions. The SCE preparation consisted
      of sugar cane extract (20%) and oilcake of rice bran (80%). SCE (500 mg/kg of
      body weight per day) was fed to weanling pigs on 3 consecutive days per week for
      4 weeks. The results showed a significant enhancement of cytotoxicity of natural
      killer (NK) cells and phagocytosis by neutrophils and monocytes, compared to
      untreated pigs. The enhancement of NK cell function may have protected against
      porcine reproductive respiratory syndrome (PRRS), as there was a reduction in
      seroconversion rates in treated pigs. Moreover, SCE-treated pigs showed a 7.87%
      growth enhancement compared with untreated controls. Thus SCE produces an
      immunostimulative effect on porcine innate immunity that may provide protection
      against pathogens.

PMID- 15997187
TI  - Ventilatory failure and successful management for a dog with severe cervical
      meningioma.
AB  - A 12-year-old intact male mongrel dog with a weight of 22 kg was referred with a
      complaint of progressive tetraparesis. Cervical myelography revealed an
      intradural-extramedullary mass at the second cervical vertebra. After computed
      tomography (CT) under general anesthesia, the patient showed dyspnea and cyanosis
      caused by insufficient movement of the chest wall. Positive pressure ventilation
      was therefore initiated. Hemilaminectomy and partial mass removal were performed
      12 hr after the CT. The mass was histopathologically diagnosed as meningioma.
      Gradual weaning from the mechanical ventilation lasted for 80 hr after the
      operation. The patient eventually recovered from the ventilatory failure and the
      tetraparesis at approximately 6 and 14 days after the operation, respectively.

PMID- 15997188
TI  - Male Pseudohermaphroditism in a raccoon dog (Nyctereutes procynoides).
AB  - A wild raccoon dog (Nyctereutes procynoides) which died due to a traffic accident
      on 18 October 2001, and was determined to be 4.5 years old, was examined. Visual
      appearance of the external genitalia in this animal showed to be female with a
      large penis-like clitoris protruding from the vulvar juncture. Visual examination
      of the internal genitalia revealed that the animal possessed both testes and
      uterus. Histological appearance of the removed gonads showed only Sertoli cells
      but no spermatogenesis. Using polymerase chain reaction with skin biopsy directed
      against the sex-determining region on the Y chromosome (SRY) gene, the genomic
      SRY gene was expressed as a single band and sequenced. Based on these findings,
      this raccoon dog was diagnosed as male pseudohermaphrodite.

PMID- 15997189
TI  - Gizzard spirurid nematode Acuaria skrjabini in Japanese tree sparrows and a gray
      starling from Tokyo.
AB  - Gastrointestinal helminths were collected from 49 Japanese tree sparrows (Passer
      montanus saturatus) in Tokyo, Japan. In 16 sparrows, 1-9 (average, 3.5) gizzard
      spirurid nematodes (Acuaria skrjabini Ozerskaya, 1926) were found embedded in the
      mucosa of the gizzard. In addition, Capillaria sp., Platynosomum passeri
      Yamashita et Tsumura, 1962, and a hymenolepidid cestode were collected from 1, 2,
      and 1 sparrows, respectively. A sexually mature A. skrjabini female and 3 males
      were found also in a young gray starling (Sturnus cineraceus) that was found dead
      in the same area after failure to leave the nest. Starlings are a new host record
      for this spirurid species. Until this study, this gizzard spirurid species has
      not been recorded in this country or the Far East region.

PMID- 15997190
TI  - The absence of Rhodococcus equi in Mongolian horses.
AB  - In native Mongolian horses, the incidence and distribution of Rhodococcus equi
      are poorly understood. One hundred and fourteen equine fecal samples and 71 soil
      samples were collected from the camp sites of 26 nomadic families located in
      three areas less than 100 km from Ulaanbaatar, Mongolia. Five fecal samples were
      also collected from foals of Przewalski's Horses introduced into the Hustai
      National Park, Mongolia. No R. equi was isolated from the Mongolian horses or the
      soil samples. However, three colonies of R. equi were isolated from two fecal
      samples collected from foals of Przewalski's Horses. These isolates were
      avirulent, with neither 15- to 17-kDa antigens (VapA) nor a 20-kDa antigen (VapB)
      genes being detected. We concluded that native Mongolian horses and their
      environment appear free from contamination with R. equi.

PMID- 15997191
TI  - Changes in activities of enzymes related to energy metabolism in canine lymphoma
      cells.
AB  - Alterations in the activities of enzymes related to energy metabolism in canine
      lymphoma cells were investigated. Cytosolic pyruvate kinase (PK) and
      mitochondrial malate dehydrogenase (MDH) activities in lymphoma cells were
      significantly higher than those in lymphocytes obtained from lymph nodes of
      healthy dogs, whereas cytosolic lactate dehydrogenase (LDH) activity was
      significantly lower in lymphoma cells. The cytosolic M/L ratio (MDH activity/LDH
      activity), which is considered to be a good indicator of energy metabolism
      related to glucose utilization in animal tissues, was significantly higher in
      lymphoma cells than in the normal lymphocytes.

PMID- 15997192
TI  - Tension pneumoperitoneum due to gastric perforation in a cat.
AB  - A 14-year-old spayed female cat weighing 2.3 kg developed tension
      pneumoperitoneum that progressed for 6 hr. Abdominocentesis was performed and 1.3
      L of gas was aspirated after which the cat's respiratory condition improved. The
      next day, the cat's abdomen redistended, and laparotomy was performed. A gastric
      perforation was noted and sutured after the margin was resection. The cat showed
      a good physical condition without any gastrointestinal signs at 6 months after
      surgery.

PMID- 15997193
TI  - Cerebrospinal fluid S-100B concentrations in normal and diseased cattle.
AB  - We measured the concentrations of S-100B, a marker protein used in humans to
      detect brain damage, in the cerebrospinal fluid (CSF) of clinically normal cattle
      (n=15, mean age +/- SD: 31.8 +/- 37.5 months) and of cattle with various
      inflammatory disorders (n=43, 70.6 +/- 31.9 months). The mean +/- SD CSF S-100B
      level was 2.9 +/- 1.6 ng/ml in the normal group and 7.0 +/- 7.4 ng/ml in the
      diseased group. Thirteen diseased cattle that had developed no obvious
      neurological signs showed abnormally high S-100B concentrations (> 8.0 ng/ml),
      whereas the two cattle with neurological disorders did not. No particular disease
      could be related to the S-100B rise. Therefore, it remains inconclusive whether
      measurement of CSF S-100B concentration is useful in veterinary neurological
      diagnosis.

PMID- 15997194
TI  - Unusual metastasis of malignant aortic body tumor to multiple bones in a dog.
AB  - Unusual metastasis of malignant aortic body tumor to multiple bones was detected
      in a 5-year-old female English Setter dog. Radiographs exhibited an abnormal mass
      in the base of heart and osteolytic lesions in the bodies of T11 and L2
      vertebrates, body of right femur, right proximal humoral epiphysis and
      infraspinous fossa near to the neck of right scapula. At necropsy, multiple tumor
      masses of various sizes were observed also in the bones as well as the heart base
      and tracheobronchial lymph node. Tumor masses of L2 and T11 protruded into the
      vertebral canal and compressed corresponding sites of spinal cord, leading to
      paraplegia. Histopathologically, the tumor cells, arranged in sheets or nests,
      were polyhedral, lightly eosinophilic, finely granular cytoplasm with mostly
      round to oval nucleus and had scattered bizarre giant cells. Ultrastructural
      study revealed the characteristic findings that tumor cells contained a large
      number of small, electron-dense, membrane-limited secretory granules in
      cytoplasm. This is thought to be an extremely rare case having multiple bone
      metastases of a malignant aortic body tumor.

PMID- 15997195
TI  - Antifungal activities of the combination of tacrolimus and itraconazole against
      Trichophyton mentagrophytes.
AB  - Tacrolimus was reported to have no antifungal activity against dermatophytes, but
      it might show a synergistic fungicidal activity with azoles against dermatophytes
      as in the case of pathogenic yeasts. Therefore, we examined the antifungal
      activity of tacrolimus combined with itraconazole (ITZ) against five strains of
      Trichophyton mentagrophytes by measuring cell growth and performing MIC (minimum
      inhibitory concentration) testing. The mean colony diameter of T. mentagrophytes
      on 1/10 diluted Sabouraud dextrose agar (dSDA) with tacrolimus combined with ITZ
      was significantly shorter than that on dSDA with tacrolimus or ITZ. MICs of
      tacrolimus, ITZ, and tacrolimus combined with ITZ against T. mentagrophytes were
      determined, respectively. The results revealed a synergistic activity of
      tacrolimus in combination with ITZ against T. mentagrophytes.

PMID- 15997196
TI  - Chronic myocardial infarction due to arteriosclerosis of coronary arteries
      followed by acute thromboembolism of caudal abdominal aorta in a cat.
AB  - A 10-year-old cat with the paresis of hind limbs was initially diagnosed as a
      hypertrophic cardiomyopathy followed by acute thromboembolism of caudal abdominal
      aorta from the findings of the medical examinations. However, this case was
      proved to be an chronic myocardial infarction due to arteriosclerosis of coronary
      arteries by the pathologic diagnosis. In the left ventricular, the hypertrophy
      and the narrowing were slight, and a coagulative infarction was seen obviously.
      The intramural coronary arteriosclerosis showed thickening of the wall due to
      medial hyperplasia by fibrosis, and arterial stenosis. Myocardial infarction and
      arteriosclerosis are scarcely any reports of these lesions in cats. This case is
      valuable for an extremely rare case of myocardial infarction in the cat.

PMID- 15997197
TI  - Japanese black cattle with ateliosis showed lower insulin responses during
      glucose tolerance test.
AB  - In order to determine insulin secretability and glucose utilization, a glucose
      tolerance test was performed in ateliotic cattle of 2 paternal strains; MHO and
      HSK cattle. MHO and HSK cattle showed different endocrine patterns in our
      previous study. Area under the insulin concentration curves (insulin-AUC) in the
      ateliotic cattle were significantly lower (122.3 +/- 59.4 ng.min/ml and 99.2 +/-
      24.8 ng.min/ml for MHO and HSK cattle, respectively) than the control cattle
      (420.2 +/- 175.2 ng.min/ml). These low insulin responses to GTT may have an
      influence on growth retardation in MHO and HSK cattle.

PMID- 15997198
TI  - Differences in the outcomes and treatments of extensively burned patients between
      a Chinese hospital and a Japanese hospital.
AB  - To know the therapeutic level at one's own institute is important and contributes
      to improving the treatment of patients. We compared the outcomes of extensively
      burned patients between a Chinese hospital and a Japanese hospital in order to
      identify the differences in the clinical treatment of severe burn patients.
      Thirty-four burn patients who were admitted to the National Defense Medical
      College Hospital (NDMC) in Japan and 95 burn patients who were admitted to the
      Changhai Hospital of the Second Military Medical University (SMMU) in China from
      January 1999 to December 2003 were studied. All patients were transported to the
      respective hospitals within 3 days after suffering burns and their total body
      surface area of burns was greater than 20%. Fourteen of the 34 patients (41.2%)
      at NDMC hospital and 1 of the 95 patients (1.1%) at SMMU hospital were injured by
      attempted suicide; namely, the suicide rate was significantly higher in the
      patients at NDMC hospital (p < 0.001). Moreover, the age (p = 0.005) and
      inhalation rate (p = 0.013) were significantly higher at NDMC hospital than those
      at SMMU hospital. Consequently, the survival rate at SMMU was higher than at NDMC
      in the patients with a burn surface area of greater than 80% or with a burn index
      of greater than 60. The excellent outcomes of the extensively burned patients at
      SMMU were in part due to the fact that Chinese doctors tend to perform an
      immediate tracheostomy and a traditional Chinese operation with alloskin, called
      microskin grafting or intermingled skin grafting.

PMID- 15997199
TI  - Usefulness of the thyrotropin-releasing hormone test in pre-clinical acromegaly.
AB  - Acromegaly is caused primarily by pituitary growth hormone (GH)-secreting tumors.
      It is usually recognized because of characteristic manifestations, and diagnosed
      clinically. However, there exists a mild stage of acromegaly, which poses a
      diagnostic problem due to the absence of typical clinical manifestations. Here we
      present four patients with pre-clinical acromegaly, who showed minimal
      acromegaloid features with elevated levels of insulin-like growth factor-I. Basal
      GH levels were within normal levels in 3 of 4 cases, while insulin-like growth
      factor-I levels were elevated above normal in all cases. Plasma GH levels were
      elevated in response to thyrotropin-releasing hormone (TRH) in all cases,
      indicating a diagnostic value of the TRH stimulation test. In contrast, an oral
      glucose tolerance test was not useful for the diagnosis, because of the low GH
      levels (less than 1 ng/ml) and/or secondary to diabetes mellitus. In response to
      a dopamine agonist, GH levels were increased in the two cases, whereas GH levels
      were decreased or remained unchanged in the other two cases. We therefore suggest
      that the TRH stimulation test would be helpful to examine the presence of pre
      clinical acromegaly. Diagnosis of the early stages of acromegaly is important to
      prevent progression to overt acromegaly.

PMID- 15997200
TI  - Genotoxicity of thallium-201 in patients with angina pectoris undergoing
      myocardial perfusion study.
AB  - Thallium-201 (201Tl) has been widely used as a nuclear reagent for myocardial
      blood flow imaging. The purpose of this study was to investigate genotoxic
      effects of 201Tl in patients with angina pectoris (n = 21), who had undergone
      myocardial perfusion imaging. Lymphocytes were isolated from each patient before,
      and 3, 30 and 90 days after 201Tl administration (111 MBq, 3 mCi) and were
      analyzed for chromosomal aberrations, sister chromatid exchanges, mitotic index
      and replicative index. There were significant increases in chromosomal
      aberrations and sister chromatid exchanges 3 days after 201Tl administration (p <
      0.001), although no difference was noted in these values after 30 and 90 days (p
      > 0.05). Moreover, decreased mitotic index and replicative index were noted after
      3 days of 201Tl administration (p < 0.001). These results suggest that the
      administration of 201Tl for myocardial blood flow imaging may induce genetic
      damage.

PMID- 15997201
TI  - Assessment of salivary and serum antioxidant vitamins and lipid peroxidation in
      patients with recurrent aphthous ulceration.
AB  - Recurrent aphthous ulceration (RAU) is a common oral mucosal disorder
      characterized by recurrent, painful oral aphthae. Although the exact cause of RAU
      is not known, local trauma, microorganisms, nutritional deficiencies, hormonal
      changes, genetics, and immunological factors have been suggested to contribute to
      its pathogenesis. The aim of this study was to assess the level of lipid
      peroxidation and status of antioxidant vitamins in patients with RAU. Thirty
      patients with RAU and 20 healthy controls were recruited. Vitamins A, E, and C
      and malondialdehyde (MDA) levels were measured in both serum and saliva of
      patients with RAU and control subjects by high performance liquid chromatography.
      Levels of vitamins A, E and C in both fluids were significantly lower (p < 0.05
      for vitamins A and E, and p < 0.005 for vitamin C, respectively) in patients with
      RAU than in healthy control subjects. Conversely, the levels of MDA in serum and
      saliva were significantly higher (p < 0.005) in patients with RAU than in the
      control group. Furthermore, strong and highly significant correlation was found
      between serum and salivary levels of vitamins A, E and C, and MDA in patients
      with RAU (r > or = 0.90, p < 0.0001). The present study demonstrates that the
      serum and saliva levels of selected antioxidant vitamins are lower, while the
      degree of lipid peroxidation, as judged by the MDA levels, is higher in patients
      with RAU than in the control subjects. This is the first to measure specific
      antioxidant levels in both saliva and blood in the same patients, and indicates
      that the non-enzymatic anti-oxidant ability is impaired in patients with RAU.

PMID- 15997202
TI  - Exercise training as an adjunct to orlistat therapy reduces oxidative stress in
      obese subjects.
AB  - The anti-obesity drug orlistat promotes weight loss and improves obesity-related
      risk factors, but its effect on oxidative stress is not clear yet. Orlistat
      reduces dietary fat absorption, which may have effects on fat soluble vitamins
      especially the antioxidant vitamins A and E. The aim of this study was to
      determine and compare the effects of weight loss achieved by orlistat therapy and
      a combination of orlistat with aerobic exercise training on lipid peroxidation
      and antioxidative defense in obese subjects. Total of 24 obese subjects were
      randomly assigned to receive 12-week treatment with hypocaloric diet-orlistat
      (120 mg three times daily) (DO group) or diet-orlistat-exercise (DOE group).
      Serum levels of malondialdehyde (MDA), a marker for lipid peroxidation, and
      vitamins A and E were measured by high performance liquid chromatography at
      baseline and at the end of the treatment. Body weight and fat mass were
      significantly reduced in the two groups (p < 0.001). In the DO group, the MDA
      levels remained unchanged (p = 0.59), while vitamins A (p < 0.01) and E (p <
      0.001) were significantly decreased. In contrast, the subjects treated with DOE
      exhibited marked decreases in MDA (p = 0.002) and a small but significant
      decrease in vitamins A (p = 0.003) and E (p = 0.003). Thus, orlistat therapy
      alone caused a significant reduction in antioxidative capacity without affecting
      oxidative stress, whereas orlistat in combination with exercise training provided
      a significant decrease in MDA levels. The beneficial effect of aerobic exercise
      as an adjunct to the orlistat therapy is of importance with regard to the obesity
      associated risk factors.

PMID- 15997203
TI  - Intakes of calcium and other nutrients related to bone health in Japanese female
      college students: a study using the duplicate portion sampling method.
AB  - The purposes of this study were to determine intakes of nutrients related to bone
      health, such as calcium (Ca), phosphorus (P), sodium (Na), potassium (K), and
      protein, in Japanese female college students, using the duplicate portion
      sampling method, and to identify possible lifestyle factors explaining their
      calcium intakes. Subjects were 106 Japanese female college students aged 19-23
      years. All foods in the duplicate portions, as eaten by the subjects during a
      three-weekday period, were collected. The minerals and protein in the food
      samples were analyzed. Life-style information was obtained by interview. Levels
      of cognitive eating restraint (CER) were assessed by the Three-Factor Eating
      Inventory. Average intakes of dietary Ca, P, Na, K, and protein were 380 (SD 209)
      mg/day, 649 (SD 212) mg/day, 2,535 (SD 847) mg/day, 1,108 (SD 429) mg/day, and
      41.7 (SD 12.6) g/day, respectively. Ca intake was significantly associated with
      the frequency of milk intake (R2 = 0.278, p < 0.001), intake of other dairy
      products (R2 = 0.338, p < 0.001), and meal skipping (R2 = 0.161, p < 0.001), but
      not with CER score (p = 0.378). Female college students are at high risk for poor
      Ca nutrition. Low intake of nutrients relevant to bone health is considered to
      adversely affect bone metabolism in young women.

PMID- 15997204
TI  - Endocrine disruptive effects of polychlorinated biphenyls on the thyroid gland in
      female rats.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Aroclor
      1221 (A1221) and Aroclor 1254 (A1254) are commercial PCB mixtures with low and
      high number of chlorination, respectively. We have comparatively investigated
      effects of A1221 and A1254 on serum levels of thyroid hormones and thyroid gland
      histology in adult female Wistar rats. Animals were subcutaneously injected with
      A1221 (10 mg/kg) or A1254 (10 mg/kg) for six weeks. One group of animals served
      as control. At the end, all animals were decapitated and trunk blood collected.
      Serum levels of triiodothyronine (T3) and thyroxine (T4) were measured by the
      electrochemiluminescence immunoassay method. Thyroid glands were removed for
      histopathological examination under light microscopy. Serum total T4 levels were
      significantly increased in A1221- and A1254-treated rats (p < 0.05). Serum free
      T4 levels were significantly increased in the A1254-treated rats (p < 0.01), but
      not in the A1221-treated rats. In contrast, the treatment with A1221 caused a
      significant increase in serum free T3 concentrations (p < 0.05) but not with
      A1254. Notably, either A1221 or A1254 caused distinct histopathological changes,
      such as formation of many microfollicles in the thyroid gland, which mimic the
      changes seen in thyrotoxicosis. In conclusion, both PCB mixtures induce toxic
      effects in the thyroid gland regardless of their degree of chlorination. We
      suggest that these environmental contaminants may disrupt thyroid hormone
      homeostasis in exposed individuals and thus pose a threat to human health.

PMID- 15997205
TI  - Acid sphingomyelinase: relation of 93lysine residue on the ratio of intracellular
      to secreted enzyme activity.
AB  - Acid sphingomyelinase (ASM) is the lysosomal enzyme responsible for the
      hydrolysis of sphingomyelin to ceramide and phosphocholine. An inherited
      deficiency of this enzymatic activity results in the Type A and B forms of
      Niemann-Pick disease (NPD). ASM is also readily secreted from cultured cells and
      can rapidly move from lysosomes to the cell surface upon stimulation by cytokines
      and other factors. Recent interest has focused on the role of this secreted/cell
      surface enzyme in ceramide-mediated signal transduction. We therefore sought to
      understand the mechanism(s) that might regulate intracellular targeting and
      secretion of this important hydrolase. Most lysosomal proteins are targeted to
      lysosomes in mammalian cells via the mannose 6-phosphate recognition system.
      Using cultured skin fibroblasts from I-cell disease patients, in which one of the
      enzymes responsible for mannose phosphorylation, GlcNAc-phosphotransferase, is
      deficient, we determined ASM activities in cell homogenates and media. The ratio
      of secreted to intracellular activity was approximately 8-fold greater in I-cell
      than in normal cells, indicating that mannose phosphorylation is important in the
      trafficking of this hydrolase. Most of the secreted activity required Zn+2 for
      full activity, supporting the concept that intracellular exposure of ASM to zinc
      within lysosomes is required for enzymatic activation. The recognition of
      lysosomal proteins by GlcNAc-phosphotransferase is mediated by protein structure,
      and a specific three-dimensional arrangement of lysine residues exposed on the
      surface of several enzymes has been shown to be critical for mannose
      phosphorylation. Alanine scanning mutagenesis of thirteen lysine residues in ASM
      demonstrated that 93lysine residue plays a critical role in ASM targeting since
      the K93A mutant had reduced intracellular activity, but enhanced secreted
      activity that was zinc responsive.

PMID- 15997206
TI  - C-reactive protein levels in non-obese pregnant women with gestational diabetes.
AB  - A low-grade systemic inflammation is concomitant in diabetes. There is a
      pathophysiological relation between gestational diabetes mellitus and type 2
      diabetes mellitus, which was further supported by significantly elevated risk of
      type 2 diabetes in women with a history of previous gestational diabetes
      mellitus. We investigated the relation between low-grade systemic inflammation
      expressed as C-reactive protein and gestational diabetes in non-obese pregnant
      women. This study included 20 non-obese pregnant women with gestational diabetes
      mellitus and 30 non-obese pregnant women without gestational diabetes mellitus as
      a control group. The body mass index of all the subjects were < 25 kg/m2. During
      26-28 gestational weeks 100-g oral glucose tolerance test was performed and
      simultaneously fasting C-reactive protein levels were measured. Serum median C
      reactive protein level was higher in patients with gestational diabetes mellitus
      (p = 0.0001). C-reactive protein was strongly associated with glycemic parameters
      and weight gain during pregnancy. A model consisting of glucose intolerance, age,
      parity, and weight gain during pregnancy accounted for 61% of the variance in log
      C-reactive protein. We demonstrated that serum C-reactive protein level was
      related with gestational diabetes mellitus and weight gain during pregnancy in
      late second and early third trimesters.

PMID- 15997207
TI  - Cognitive decline in patients with long-term domiciliary oxygen therapy.
AB  - Cognitive and psycho-physiological condition in patients with long-term
      domiciliary oxygen therapy (DOT) remains uncertain. A cross sectional analysis
      was performed to investigate the age-related changes in cognitive and psycho
      physiologic functions in patients with chronic respiratory failure receiving long
      term DOT. Two expert practitioners visited the patient's home and examined them
      for analysis of cognitive function, emotional status, physical activity and
      degree of dyspneic sensation. One hundred and thirty-five patients completed the
      study. Control data from a cohort of 718 community dwellers were also included in
      this study. Male patients had significantly higher rates of chronic obstructive
      pulmonary disease (71% vs 47%, p = 0.001), lower values of forced expiratory
      volume in one second (FEV1.0) % (49.7 +/- 10.3 [standard deviation, S.D.] vs 66.0
      +/- 7.5% predicted, p = 0.002) and higher Borg score, an indicator of dyspneic
      sensation, during daily exercise (3.2 +/- 0.8 [S.D.] vs 1.4 +/- 0.6, p = 0.01)
      compared with female patients. Linear regression analysis based on mean Mini
      Mental State Examination scores, an indicator of cognitive function, showed that
      age-related cognitive decline was more pronounced in female patients than in
      female controls (-0.524/year, R2 = 0.426 vs -0.120/year, R2 = 0.027, p < 0.0001),
      while there was no significant difference between male patients and male controls
      (-0.156/year, R2 = 0.054, vs -0.077/year, R2 = 0.016, p = 0.231). These results
      demonstrate that age-related cognitive decline is more exaggerated in female
      patients receiving long-term DOT which should be taken into consideration in
      caring for patients with chronic respiratory failure.

PMID- 15997208
TI  - Discrepancy in polysomnography scoring for a patient with obstructive sleep apnea
      hypopnea syndrome.
AB  - Overnight polysomnography (PSG) is indispensable for diagnosis of obstructive
      sleep apnea hypopnea syndrome. However, studies on interscorer agreement on PSG
      scoring between laboratories are few. The purpose of this study was to examine
      the reliability of interscorer agreement on PSG scoring among 16 sleep
      laboratories in Japan. We found a relatively moderate interscorer reliability of
      the index of oxygen desaturation and arousal during sleep, but a relatively low
      reliability of the index of transient reduction in and complete cessation of
      breathing (apnea hypopnea index). The median rate of interscorer coincidence of
      sleep staging was the lowest for slow wave (deep) sleep (23.5%), followed by
      those for Stage 1 (59.8%), Wake (73.2%) and Stage 2 (74.2%) in this order, and
      rapid eye movement was the most reliably identified stage (91.3%). The median
      rate of interscorer coincidence for all stages was 71.8%. The present study
      demonstrates that scorers tend to analyze PSG data according to a relatively
      empirical decision as opposed to a rule-dependent decision. Further detailed
      scoring manuals are required to decrease the interscorer discrepancy in PSG
      scoring.

PMID- 15997209
TI  - Natural course of hematoma in lateral rectus muscle followed by magnetic
      resonance imaging.
AB  - We report a patient with a spontaneous intramuscular hematoma in the lateral
      rectus muscle of the eye that resolved without medication with maintenance of
      good vision. A 40-year-old woman presented with ocular pain and exophthalmos in
      her right eye. She had no history of trauma or surgery. Exophthalmos and
      limitation of abduction and supraduction of her right eye were present at the
      initial examination. Magnetic resonance (MR) images showed an intramuscular
      hematoma in the right lateral rectus muscle. Her other ocular findings were
      within normal limits. Five months later without any treatments, the MR images
      were within normal limits, and her ocular signs and symptoms were completely
      resolved. Careful observations including MR imaging is sufficient for patients
      with a spontaneous intramuscular hemorrhage in the extraocular muscle, and the
      visual prognosis is good.

PMID- 15997210
TI  - [Pathogenic factors of vibrios with special emphasis on Vibrio vulnificus].
AB  - Bacteria of the genus Vibrio are normal habitants of the aquatic environment and
      play roles for biocontrole of aquatic ecosystem, but some species are believed to
      be human pathogens. These species can be classified into two groups according to
      the types of diseases they cause: the gastrointestinal infections and the
      extraintestinal infections. The pathogenic species produce various pathogenic
      factors including enterotoxin, hemolysin, cytotoxin, protease, siderophore,
      adhesive factor, and hemagglutinin. We studied various pathogenic factors of
      vibrios with special emphasis on protease and hemolysin of V. vulnificus. V.
      vulnificus is now recognized as being among the most rapidly fatal of human
      pathogens, although the infection is appeared in patients having underlying
      disease(s) such as liver dysfunction, alcoholic cirrhosis or haemochromatosis. V.
      vulnificus protease (VVP) is thought to be a major toxic factor causing skin
      damage in the patients having septicemia. VVP is a metalloprotease and degrades a
      number of biologically important proteins including elastin, fibrinogen, and
      plasma proteinase inhibitors of complement components. VVP causes skin damages
      through activation of the Factor XII-plasma kallikrein-kinin cascade and/or
      exocytotic histamine release from mast cells, and a haemorrhagic lesion through
      digestion of the vascular basement membrane. Thus, the protease is the most
      probable candidate for tissue damage and bacterial invasion during an infection.
      Pathogenic roles and functional mechanism of other factors including hemolysins
      of V. vulnificus and V. mimicus are also shown in this review article.

PMID- 15997212
TI  - Collection of medical drug information in pharmacies: Drug Event Monitoring (DEM)
      in Japan.
AB  - To establish a system for collecting and reporting information from community
      pharmacists such as that on adverse effects, the Japan Pharmaceutical Association
      (JPA) conducts Drug Event Monitoring (DEM). In the fiscal year 2002, a survey was
      carried out to clarify the incidence of sleepiness due to antiallergic drugs. The
      investigated active ingredients were ebastine, fexofenadine hydrochloride,
      cetirizine hydrochloride, and loratadine. Community pharmacists asked the
      following question to patients who visited their pharmacies: "Have you ever
      become sleepy after taking this drug?" During a 4-week survey period, reports of
      94256 cases were collected. To evaluate the incidence of sleepiness, we analyzed
      cases in which reports showed alleged absence of concomitant oral drugs, and drug
      use in conformity with the dose and method described in package inserts. The
      incidence of sleepiness was significantly different among the drugs (chi(2)-test,
      p<0.001). The observed incidences of sleepiness due to the drugs (8.8-20.5%) were
      higher than those described in each package insert (1.8-6.35%). This may be
      because an active question was used ("Have you ever become sleepy after taking
      this drug?"). Active intervention by pharmacists may be useful for collecting
      more information on improvement in the QOL of patients and safety. In addition,
      the pharmacists were asked to report events other than "sleepiness" in the free
      description column of the report. Some symptoms not described in the package
      inserts were reported, suggesting that DEM may lead to the discovery of new
      adverse effects. These results suggest that community pharmacists have a good
      opportunity to collect information in DEM, and safety information such as that on
      adverse effects can be obtained from pharmacies.

PMID- 15997211
TI  - Behavioral and neurochemical alterations following thiamine deficiency in
      rodents: relationship to functions of cholinergic neurons.
AB  - Memory deficits are induced during the late stage (20-25 days) of thiamine
      deficient (TD) feeding. In this review, the role of cholinergic neurons on the
      memory deficit induced by TD feeding are summarized. Although memory deficit
      cannot be suppressed by an injection of thiamine once it appears, such impairment
      was found to be protected by early treatment with thiamine during TD feeding.
      Administration of muscarinic M(1) agonist McN-A-343 reversed the memory deficit
      observed in TD mice, although the muscarinic M(2) antagonist methoctramine did
      not. The "kampo" (traditional herbal) medicine, "kami-untan-to" (KUT), protected
      against the memory deficit observed in TD mice. Choline acetyltransferase (ChAT)
      fluorescence intensity, a marker of presynapse of cholinergic neurons, was
      decreased in the cortex and hippocampus at an early stage (14th day) of TD, and
      it was decreased in a wide range of brain areas at a late stage (25th day) of TD.
      Early KUT treatment inhibited the reduction of ChAT in the hippocampus of TD
      mice. These findings suggested that the memory deficit may be caused by a
      reduction in the cholinergic function at an early stage of TD, and that the
      activation of cholinergic neurons may play an important role in the improvement
      of TD-induced memory deficit.

PMID- 15997214
TI  - [Effectiveness of methotrexate for the escape by salazosulfapyridine].
AB  - Although disease modifying anti-rheumatic drugs (DMARDs) are used in the
      treatment of rheumatoid arthritis (RA), the selection of agents in the case of
      relapse (escape phenomenon) lacks clear-cut standards. We compared the
      effectiveness in a salazosulfapyridine and then methotrexate (SASP-->MTX) group
      with that in the mothotrexate (SASP+MTX) group after escape phenomenon expression
      in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) data.
      Outpatients of the Matsubara Mayflower Hospital with a history of DMARD
      administration during the 4 years prior to May 2003 were studied. The CRP level
      in the SASP-->MTX group (n=8) after the escape phenomenon expression showed a
      decline after 3 months, but no decline was seen even after 3 months the two in
      the CRP level in the SASP+MTX group (n=10). However, the difference between
      groups was not significant. The fluctuation in ESR was similar to that in CRP.
      However, ESR was significantly lower in the SASP-->MTX group 20 weeks after
      escape phenomenon expression. In evaluating treatment effectiveness after escape
      phenomenon expression in each group, SASP-->MTX was effective in 10 and SASP+MTX
      in 7 patients. Side effects necessitated cessation of treatment in 1 patient in
      the SASP-->MTX group. Treatment continued in 4 patients in the SASP-->MTX group
      and 2 in the SASP+MTX group, even though side effects occurred. It should be
      borne in mind that combination therapy often has greater clinical benefit than
      single agent therapy but not always.

PMID- 15997215
TI  - Maize in pre-Columbian China.
AB  - A certain Chinese herbal book presented to the emperor in 1505 shows a drawing of
      maize under the caption of Yiyi-ren (Job's Tears). Also, a Chinese poem written
      around 1368 contains a term yumi, which indicates maize. These new findings offer
      clear evidence that maize existed in China in the pre-Columbian era, or before
      1492. Details of this evidence are discussed here.

PMID- 15997213
TI  - [Construction and evaluation of a cancer chemotherapy regimen database using an
      electronic medical chart network].
AB  - PURPOSE: There are many regimens for cancer chemotherapy, and thus information
      management is complicated. It is thought that the safe and appropriate use of
      cancer chemotherapy can be achieved by developing a system that involves
      information-sharing among medical staff. A system facilitating the choice of
      regimen was developed in our institution using an electronic medical chart
      network. In addition, a questionnaire was distributed to evaluate the usefulness
      of the cancer chemotherapy regimen database (DB). METHODS: Microsoft Access 2000
      was used for the DB. Microsoft Internet Information Services Ver. 6.0 included in
      the Windows 2003 Server was used as the management software of the Web-version
      DB. RESULTS: With the Web-version DB, it was possible to offer chemotherapy
      regimen information to all departments in the hospital. The DB received an
      excellent evaluation based on the questionnaire results. The reasons for this
      were the exceptional ability to share information among medical staff and the
      appeal of a checking system. CONCLUSION: Obtaining information regarding cancer
      chemotherapy regimens became easier with the Web-version DB, which received an
      excellent evaluation by all medical staff. Proactive use of the Web-version DB
      can contribute to proper cancer chemotherapy choice and strengthening of hospital
      risk management.

PMID- 15997216
TI  - Antiatherogenic effects of phyllanthus emblica associated with corilagin and its
      analogue.
AB  - Oxidized low-density lipoprotein (ox-LDL) is the main etiologic factor in
      atherogenesis, and antioxidants are accepted as effective treatment of
      atherosclerosis. The aim of this study was to clarify whether the mechanism of
      the antiatherogenic effects of the herb Phyllanthus Emblica, which is widely used
      to treat atherosclerosis-related diseases, is associated with ox-LDL via its
      compounds of soluble tannin, corilagin (beta-1-O-galloyl-3,6-(R)
      hexahydroxydiphenoyl-d-glucose), and its analogue Dgg16 (1,6-di-O-galloyl-beta-d
      glucose). Human umbilical vein endothelial cells, ECV-304, were incubated with ox
      LDL (50 mg/l), treated with corilagin or Dgg16 at different doses (0.0001-0.1
      mmol/l), and then incubated with monocytes. Malondialdehyde (MDA) in the culture
      media was determined and the number of monocytes adhering to ECV-304 cells was
      counted with cytometry. In another experiment, the rat vascular smooth muscular
      cells (VSMC) were incubated in media with or without ox-LDL (50 mg/l), and with
      corilagin or Dgg16 also at different doses (0.0001-0.1 mol/l), the proliferation
      of which was assayed with MTT. The results showed that both corilagin and Dgg16
      were able to decrease MDA, prevented ECV-304 cells from being adhering to by
      monocytes, and inhibited VSMC proliferation activated by ox-LDL. The results
      suggest that the two compounds are effective in inhibiting the progress of
      atherosclerosis by alleviating oxidation injury or by inhibiting ox-LDL-induced
      VSMC proliferation, which may be promising mechanisms for treating
      atherosclerosis.

PMID- 15997217
TI  - [Introduction of active learning and student readership in teaching by the
      pharmaceutical faculty].
AB  - We have introduced improvements and new approaches into our teaching methods by
      exploiting 4 active learning methods for pharmacy students of first year. The 4
      teaching methods for each lesson or take home assignment are follows: 1) problem
      based learning (clinical case) including a student presentation of the clinical
      case, 2) schematic drawings of the human organs, one drawing done in 15-20 min
      during the week following a lecture and a second drawing done with reference to a
      professional textbook, 3) learning of professional themes in take home
      assignments, and 4) short test in order to confirm the understanding of technical
      terms by using paper or computer. These improvements and new methods provide
      active approaches for pharmacy students (as opposed to passive memorization of
      words and image study). In combination, they have proven to be useful as a
      learning method to acquire expert knowledge and to convert from passive learning
      approach to active learning approach of pharmacy students in the classroom.

PMID- 15997218
TI  - Guidelines for the diagnosis and therapy of the vein and lymphatic disorders.

PMID- 15997219
TI  - The case for saphenous ablation versus simple proximal ligation.
AB  - New modalities of treatment for primary varicose veins are being increasingly
      used. This is because traditional stripping and sapheno-femoral junction ligation
      is requires a general anaesthetic and is associated with postoperative pain and
      bruising. This article aims to address the evidence and long-term follow up of
      the new surgical techniques and compare them to traditional sapheno-femoral
      ligation.

PMID- 15997220
TI  - Advanced management of arteriovenous shunting malformation with transarterial
      lung perfusion scintigraphy for follow-up assessment.
AB  - AIM: The clinical assessment of arteriovenous malformations (AVMs), including
      treatment response (surgical and/or embolosclerotherapy), has traditionally been
      done by arteriography, mainly by looking for residual lesions. However,
      arteriography is disadvantaged as it is an expensive invasive test with high
      morbidity and provides only limited anatomical information at the qualitative
      level. Here, transarterial lung perfusion scintigraphy (TLPS), which was
      developed as a less invasive test for the physiologic assessment of the
      arteriovenous shunting status of AVM lesions located in the lower extremities,
      was evaluated for its ability to replace traditional arteriography as a means of
      following-up treatment results. METHODS: The shunting volume of radioisotope
      tagged macro-aggregated albumin injected into the arterial system of the affected
      limb was counted by TLPS before and after AVM treatment, as a quantitative
      measure of treatment response. The findings obtained were compared with a
      matching duplex scan, whole body blood pool scintigraphy (WBBPS) findings, and
      arteriographic findings. RESULTS: Twenty-one TLPS tests were performed as follow
      up assessments on 15 patients with AVM in the extremity, who underwent
      multistaged embolo/sclerotherapy alone or combined with surgical therapy. These
      21 TLPS findings, including 6 interim TLPS results (average 16 months follow-up),
      provided quantitative measurements of lesion reductions as percentile ratios
      versus the baseline pretreatment values. Matching posttreatment duplex scan (14
      out of 17 sets) and WBBPS (12 out of 15 sets) findings confirmed the
      posttreatment TLPS assessment. RESULTS: In addition, all 12 available
      arteriographic studies confirmed the matching TLPS findings. CONCLUSIONS: TLPS
      can provide accurate information on shunting volume reduction, occurring in
      response to various treatments during or after the completion of therapy. TLPS,
      therefore, may be able to replace arteriography, and provide a reliable means of
      follow-up assessment for the determination of the future treatment strategy.

PMID- 15997221
TI  - Is screening of abdominal aortic aneurysm effective in a general practice
      setting?
AB  - AIM: This prospective study was conducted to assess feasibility, patients'
      acceptability and impact of ultrasound screening on rupture rate of abdominal
      aortic aneurysms (AAAs). METHODS: A population based sample of men (n=2709), aged
      over 60 years, covering 11 general practices was offered ultrasound screening
      between January 1996 and December 2003. The presence of risk factors for
      arteriosclerosis and annual rupture rates for AAAs were analyzed. RESULTS: Of the
      2709 patients approached, 2561 (95%) accepted and 161 (6%) did not attend. A
      total number of 81 (3.4%) patients (average age: 71 years) were identified with
      an AAA, of which 59 were small (<5 cm) and 22 large AAAs (>5 cm). The most common
      risk factors identified in patients with AAA were smoking/ex-smoking (n=68, 84%)
      and hypertension (n=32, 40%). The overall annual rupture rate was reduced from
      47% in 1996 to 14% in 2003. CONCLUSIONS: Ultrasound screening for AAA is
      feasible, acceptable by elderly male patients in a primary care setting and
      reduces the incidence of ruptured AAAs.

PMID- 15997222
TI  - Looped reconstruction of the internal and external iliac arteries in repair of
      abdominal aortic or iliac artery aneurysm with a bifurcated graft.
AB  - AIM: The aim of our study is to describe an original technique of distal
      anastomosis of a bifurcated graft, coining looped reconstruction, and our
      preliminary clinical experience. METHODS: This technique has been applied in 16
      of 24 distal anastomoses of 12 patients with abdominal aortic aneurysm (AAA)
      and/or iliac artery aneurysm. Both the internal (IIA) and external iliac arteries
      (EIA) are transected and anastomosed with end-to-end fashion to reconstruct their
      continuity, and the limb of a bifurcated graft is anastomosed to the EIA with end
      to-side fashion. RESULTS: Operative and in-hospital death, ischemic colitis, or
      ischemia of the lower extremities including blue toe syndrome has never occurred.
      All the 28 reconstructed IIAs and EIAs have been patent in 11 patients who could
      undergo early postoperative computed tomography scans with contrast medium.
      CONCLUSIONS: The looped reconstruction of the IIA and the EIA in repair of an AAA
      and/or an iliac artery aneurysm with a bifurcated graft is an anatomically easy
      and technically simple method.

PMID- 15997223
TI  - The deceptive clinical picture of primary saphenofemoral junction aneurysms.
AB  - Venous aneurysms may remain undetected for years due to their obscure and non
      specific clinical picture. Two cases of primary saphenofemoral junction aneurysm
      are described, and their vague clinical picture is highlighted. The importance of
      increased alertness and suspicion is noted, because of the gravity of the
      possible complications of an undetected venous aneurysm, namely rupture of the
      aneurysm and/or recurrent pulmonary embolism.

PMID- 15997224
TI  - Stent placement for severe stenosis in the deep femoral artery with the occluded
      superficial femoral and popliteal arteries.
AB  - In both superficial and deep femoral artery involvement, where angioplasty of the
      former is not suitable or feasible, angioplasty of the latter seems to be the
      method of choice and is a less invasive and efficient treatment particularly for
      limb threatening ischemia, an appropriate obstruction morphology provided. The
      authors describe a case of a 73-year-old man, with a rest pain of the foot and
      intermittent cyanosis of the toe, who underwent stent placement with transluminal
      angioplasty for severe stenosis in the deep femoral artery with the occluded
      superficial femoral and popliteal artery. The patient's ankle brachial index was
      remarkably increased from 0.25 to 0.61, and the preoperative symptoms were
      improved.

PMID- 15997225
TI  - Continuous crossover femoropopliteal bypass in a 68-year-old gentleman with rest
      pain.
AB  - Patients who have had multiple previous attempts at limb salvaging surgery
      frequently go on to have an amputation. This, however, results both in
      psychological perturbation for the patient and high rehabilitation costs for the
      community. Successful limb salvage surgery therefore has an important role in
      vascular surgery. We describe the management of a patient with critical limb
      ischemia that had previously undergone multiple limb salvage procedures and whose
      limb was saved by the use of a continuous femoropopliteal crossover bypass graft.
      The patient, who may have been deemed by some as a candidate for amputation, has
      full use of his limb 6 months after surgery with ankle brachial pressure index
      readings of 0.6. Continuous femoropopliteal crossover bypass grafting is a poorly
      described surgical technique that may be appropriate in a subgroup of patients
      and may allow salvage of a limb that otherwise may have been deemed fit for
      amputation.

PMID- 15997226
TI  - Bilateral axillobrachial and external carotid artery manifestation of giant cell
      arteritis: important role of color duplex ultrasonography in the diagnosis.
AB  - A 76-year-old man was admitted to our hospital with vertigo. Previously he had
      been extensively examined because of an increased erythrocyte sedimentation rate
      without any clinical symptoms. Physical examination revealed 60 mmHg blood
      pressure difference between the two arms. Color duplex ultrasound examination
      revealed bilateral extreme narrowing of the external carotid and axillobrachial
      artery with a dark, hypo-echoic halo around the lumen. This condition was
      recognized as a specific sign for giant cell arteritis (GCA), described
      originally in cases of temporal arteritis. The diagnosis was confirmed by biopsy
      of the temporal artery. In contrast to the typical cranial form of GCA -- our
      patient showed an unusual, bilateral large-vessel manifestation. The diagnosis
      was based on ultrasound images rather than on symptoms that characterize the well
      known temporal form. This observation emphasizes the role of color duplex
      ultrasonography in the diagnosis and follow-up of GCA.

PMID- 15997227
TI  - Pharmacological characterization of nucleotide P2Y receptors on endothelial cells
      of the mouse aorta.
AB  - Nucleotides regulate various effects including vascular tone. This study was
      aimed to characterize P2Y receptors on endothelial cells of the aorta of C57BL6
      mice. Five adjacent segments (width 2 mm) of the thoracic aorta were mounted in
      organ baths to measure isometric force development. Nucleotides evoked complete
      (adenosine 5' triphosphate (ATP), uridine 5' triphosphate (UTP), uridine 5'
      diphosphate (UDP); >90%) or partial (adenosine 5' diphosphate (ADP)) relaxation
      of phenylephrine precontracted thoracic aortic rings of C57BL6 mice. Relaxation
      was abolished by removal of the endothelium and was strongly suppressed (>90%) by
      inhibitors of nitric oxide synthesis. The rank order of potency was: UDP
      approximately UTP approximately ADP>adenosine 5'-[gamma-thio] triphosphate
      (ATPgammaS)>ATP, with respective pD2 values of 6.31, 6.24, 6.22, 5.82 and 5.40.
      These results are compatible with the presence of P2Y1 (ADP>ATP), P2Y2 or P2Y4
      (ATP and UTP) and P2Y6 (UDP) receptors. P2Y4 receptors were not involved, since
      P2Y4-deficient mice displayed unaltered responses to ATP and UTP. The purinergic
      receptor antagonist suramin exerted surmountable antagonism for all agonists. Its
      apparent pKb for ATP (4.53+/-0.07) was compatible with literature, but the pKb
      for UTP (5.19+/-0.03) was significantly higher. This discrepancy suggests that
      UTP activates supplementary non-P2Y2 receptor subtype(s). Further, pyridoxal
      phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) showed surmountable (UTP,
      UDP), nonsurmountable (ADP) or no antagonism (ATP). Finally, 2'-deoxy-N6
      methyladenosine3',5'-bisphosphate (MRS2179) inhibited ADP-evoked relaxation only.
      Taken together, these results point to the presence of functional P2Y1 (ADP),
      P2Y2 (ATP, UTP) and P2Y6 (UDP) receptors on murine aorta endothelial cells. The
      identity of the receptor(s) mediating the action of UTP is not fully clear and
      other P2Y subtypes might be involved in UTP-evoked vasodilatation.

PMID- 15997228
TI  - Functional expression of the P2Y14 receptor in murine T-lymphocytes.
AB  - Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis
      has previously shown that the P2Y(14) receptor is expressed in peripheral immune
      cells including lymphocytes. Although in transfected cells the P2Y(14) receptor
      couples to pertussis toxin-sensitive G(i/o) protein, the functional coupling of
      endogenously expressed P2Y(14) receptors to the inhibition of adenylyl cyclase
      activity has not been reported. Therefore, the primary aim of this study was to
      determine whether the P2Y(14) receptor is functionally expressed in murine spleen
      derived T- and B-lymphocyte-enriched populations. RT-PCR analysis detected the
      expression of P2Y(14) receptor mRNA in whole spleen and isolated T- and B
      lymphocytes. In T cells, UDP-glucose (EC(50) = 335 nM) induced a small but
      significant inhibition (circa 20%) of forskolin-stimulated cAMP accumulation,
      suggesting functional coupling of endogenously expressed P2Y(14) receptors to the
      inhibition of adenylyl cyclase activity. In contrast, the other putative P2Y(14)
      receptor agonists UDP-galactose, UDP-glucuronic acid and UDP-N-acetylglucosamine
      had no significant effect alone but behaved as partial agonists by blocking UDP
      glucose responses. In B cells, UDP-glucose (100 microM) had no significant effect
      on forskolin-stimulated cAMP accumulation. Treatment of T cells with pertussis
      toxin (G(i/o) blocker) abolished the inhibitory effects of UDP-glucose on
      forskolin-stimulated cAMP accumulation. T-cell proliferation in response to anti
      CD3 monoclonal antibody (1 microg ml(-1)) was significantly inhibited by UDP
      glucose (59% inhibition; p[IC(50)] = 5.9 +/- 0.3), UDP-N-acetylglucosamine (37%;
      6.1 +/- 0.3), UDP-galactose (56%; 8.2 +/- 0.2) and UDP-glucuronic acid (49%; 6.3
      +/- 0.2). Interleukin-2- (5 ng ml(-1)) induced T-cell proliferation was also
      significantly inhibited by all four agonists. In summary, we have shown that the
      P2Y(14) receptor appears to be functionally expressed in murine spleen-derived T
      lymphocytes. These observations suggest that UDP-glucose and related sugar
      nucleotides presumably via the P2Y(14) receptor may play an important role in
      modulating immune function.

PMID- 15997229
TI  - Induction of cytochrome P450 1A by cow milk-based formula: a comparative study
      between human milk and formula.
AB  - During the treatment of neonatal apnea, formula-fed infants, compared to
      breastfed infants, show nearly three-fold increase in clearance of caffeine, a
      substrate of cytochrome P450 1A (CYP1A) and in part CYP3A4. However, human milk
      is known to contain higher concentrations of environmental pollutants than infant
      formula, which are potent CYP1A inducers. To gain insight into the mechanism
      underlying this apparent contradiction, we characterized CYP1A and CYP3A4
      induction by human milk and cow milk-based infant formula. The mRNA and protein
      expression of CYP1A1/1A2 were significantly induced by cow milk-based formula,
      but not by human milk, in HepG2 cells. Luciferase reporter assay demonstrated
      that cow milk-based formula but not human milk activated aryl hydrocarbon
      receptor (AhR) significantly. The cotreatment of 3,4-dimethoxyflavone, an AhR
      antagonist, abolished the formula-induced CYP1A expression. In addition, AhR
      activation by dibenzo[a,h]anthracene, a potent AhR agonist, was significantly
      suppressed by infant formula and even more by human milk. In contrast, CYP3A4
      mRNA expression was only mildly induced by formula and human milk. Consistently,
      neither formula nor human milk substantially activated pregnane X receptor (PXR).
      Effects of whey and soy protein-based formulas on the AhR-CYP1A and the PXR
      CYP3A4 pathways were similar to those of cow milk-based formula. In conclusion,
      infant formula, but not human milk, enhances in vitro CYP1A expression via an AhR
      mediated pathway, providing a potential mechanistic basis for the increased
      caffeine elimination in formula-fed infants.

PMID- 15997230
TI  - Studies on the effect of MDMA ('ecstasy') on the body temperature of rats housed
      at different ambient room temperatures.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats
      produces hyperthermia if they are housed in normal or warm ambient room
      temperature (Ta) conditions (>or=20 degrees C), but hypothermia when in cool
      conditions (Ta<or=17 degrees C). We have now investigated some of the mechanisms
      involved. MDMA (5 mg kg(-1) i.p.) produced a rapid decrease in rectal temperature
      in rats at Ta 15 degrees C. This response was blocked by pretreatment with the
      dopamine D2 receptor antagonist remoxipride (10 mg kg(-1) i.p.), but unaltered by
      pretreatment with the D1 antagonist SCH23390 (1.1 mg kg(-1) i.p). MDMA (5 mg kg(
      1)) did not alter the tail temperature of rats at Ta 15 degrees C, but decreased
      the tail temperature of rats at Ta 30 degrees C. A neurotoxic dose of MDMA (three
      doses of 5 mg kg(-1) given 3 h apart) decreased cortical and hippocampal 5-HT
      content by approximately 30% 7 days later. This lesion did not influence the rise
      in tail temperature when rats were moved from Ta 20 degrees C to 30 degrees C
      compared to nonlesioned controls, but did result in a lower tail temperature than
      that of controls when they were returned to Ta 24 degrees C. Acute administration
      of MDMA (5 mg kg(-1)) to MDMA-lesioned rats produced a sustained decrease in tail
      temperature in rats housed at Ta 30 degrees C compared to nonlesioned controls.
      These data suggest that the thermoregulatory problems previously observed in MDMA
      lesioned rats housed at Ta 30 degrees C result, partially, from their inability
      to lose heat by vasodilation of the tail, a major heat-loss organ in this
      species.

PMID- 15997231
TI  - Evolving the concept of regulation of vascular tone in humans.
AB  - Elucidation of mechanisms regulating microcirculatory vascular tone is a key
      issue in the knowledge of human pathophysiology. Anandamide is an endogenous
      lipidic cannabinoid (CB) characterized by potent vasodilator activity acting
      mainly through the activation of CB receptors, located on the vessel walls, and
      the vanilloid receptor 1, located on sensory peptidergic nerve endings within the
      external layers of vessel walls. In humans, cutaneous anandamide administration
      causes forearm skin vasodilation by activating vanilloid receptor 1 presumably on
      primary sensory nerves, while intrabrachial infusion of the same compound is
      devoid of effect on forearm muscle microcirculation. Taken together, these
      results indicate that, apart from a possible distrectual difference, the effect
      of anandamide is specific for the abluminal, but not for the endoluminal, part of
      the vessel wall. Thus, it is conceivable that, at least in the peripheral
      microcirculation, this compound could act as an autocrine/paracrine agent and not
      as a circulating hormone. In line with this possibility, it has been demonstrated
      that anandamide can be produced by macrophages and therefore its biological
      effect might increase in clinical conditions characterized by augmented activity
      of this cell line, including cardiogenic, hemorrhagic and endotoxic shock and
      even in atherosclerosis, inflammation and ischemia. Moreover, increased serum
      values of anandamide have been found in patients with endotoxic shock. However,
      decisive information concerning the role of anandamide in humans will be obtained
      when specific antagonists or inhibitors will be available. In that case, the
      anandamide system might represent a potential target for the treatment of
      important cardiovascular conditions, including severe shock.

PMID- 15997232
TI  - Dexamethasone and cardiac potassium currents in the diabetic rat.
AB  - Experiments were designed to compare effects of dexamethasone on transient
      (Ipeak) and sustained (Isus) K+ currents in control and diabetic rat myocytes.
      Ventricular myocytes were isolated from control or type 1 streptozotocin (STZ)
      induced diabetic male and female rats. Currents were measured using whole-cell
      voltage-clamp methods. Incubation of cells from control males or females with 100
      nM dexamethasone (5-9 h) significantly (P<0.005) augmented Isus (by 28-31%).
      Ipeak was unchanged. Isus augmentation was abolished by cycloheximide or
      cytochalasin D, but not by inhibition of protein kinases A or C. Inhibition of
      tyrosine kinases by genistein (but not its inactive analog genistin) prevented
      the increase of Isus by dexamethasone. In marked contrast, dexamethasone had a
      significantly (P<0.015) smaller effect on Isus (11% increase) in cells from male
      STZ-diabetic rats, as compared to control cells. However, Isus augmentation in
      cells from female STZ-diabetic rats was normal (31% increase). In ovariectomized
      diabetic rats, Isus was unchanged by dexamethasone. The reduced effect in
      diabetic males might be due to preactivation of tyrosine kinases linking
      dexamethasone to current modulation. In conclusion, type I diabetes is associated
      with gender-specific changes in sensitivity of K+ currents to glucocorticoids,
      linked to alterations in tyrosine-phosphorylated proteins.

PMID- 15997233
TI  - Vascular effects of anandamide and N-acylvanillylamines in the human forearm and
      skin microcirculation.
AB  - The endocannabinoid anandamide is an emerging potential signalling molecule in
      the cardiovascular system. Anandamide causes vasodilatation, bradycardia and
      hypotension in animals and has been implicated in the pathophysiology of
      endotoxic, haemorrhagic and cardiogenic shock, but its vascular effects have not
      been studied in man. Human forearm blood flow and skin microcirculatory flow were
      recorded using venous occlusion plethysmography and laser-Doppler perfusion
      imaging (LDPI), respectively. Each test drug was infused into the brachial artery
      or applied topically on the skin followed by a standardized pin-prick to disrupt
      the epidermal barrier. Anandamide failed to affect forearm blood flow when
      administered intra-arterially at infusion rates of 0.3-300 nmol min(-1). The
      highest infusion rate led to an anandamide concentration of approximately 1
      microM in venous blood as measured by mass spectrometry. Dermal application of
      anandamide significantly increased skin microcirculatory flow and coapplication
      of the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine
      inhibited this effect. The TRPV1 agonists capsaicin, olvanil and arvanil all
      induced concentration-dependent increases in skin blood flow and burning pain
      when administered dermally. Coapplication of capsazepine inhibited blood flow and
      pain responses to all three TRPV1 agonists. This study shows that locally applied
      anandamide is a vasodilator in the human skin microcirculation. The results are
      consistent with this lipid being an activator of TRPV1 on primary sensory nerves,
      but do not support a role for anandamide as a circulating vasoactive hormone in
      the human forearm vascular bed.

PMID- 15997234
TI  - Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model
      of neuropathic pain.
AB  - Antiepileptic drugs (AEDs) are often utilized in the treatment of neuropathic
      pain. The major AED valproic acid (VPA) is of particular interest as it is
      thought to engage a variety of different neural mechanisms simultaneously.
      However, the clinical use of VPA is limited by two rare but life-threatening side
      effects: teratogenicity and hepatotoxicity. We synthesized VPA's corresponding
      amide: valpromide (VPD), two of VPAs isomers and their corresponding amides;
      valnoctic acid (VCA), valnoctamide (VCD), diisopropyl acetic acid (DIA),
      diisopropylacetamide (DID), and VPD's congener: N-methyl-VPD (MVPD). VCD, DID and
      VPD are nonteratogenic, potentially nonhepatotoxic, and exhibit better
      anticonvuslant potency than VPA. In this study, we assessed the antiallodynic
      activity of these compounds in comparison to VPA and gabapentin (GBP) using the
      rat spinal nerve ligation model of neuropathic pain (SNL, Chung model). VCA and
      MVPD were inactive. However, VPD (20-100 mg kg(- 1)), VCD (20-100 mg kg(- 1)) and
      DID (20-90 mg kg(- 1)) produced dose-related reversal of tactile allodynia with
      ED50 values of 61, 52 and 58 mgkg(- 1), respectively. All the amides were more
      potent than VPA (ED50=269 mgkg(- 1)). The antiallodynic effect of VPA, VPD, VCD
      and DID was obtained at plasma concentrations of 125, 24, 18 and 7 mg l(- 1),
      respectively, with a good pharmacokinetic-pharmacodynamic correlation and a
      minimal lag response. VCD and DID were found to have minimal motor and sedative
      side effects at analgesic doses, and were equipotent to GBP, currently the
      leading drug in neuropathic pain treatment. Consequently, VCD and DID have
      potential to become new drugs for the treatment of neuropathic pain.

PMID- 15997235
TI  - Amadori adducts activate nuclear factor-kappaB-related proinflammatory genes in
      cultured human peritoneal mesothelial cells.
AB  - Diabetes mellitus leads to a high incidence of several so-called complications,
      sharing similar pathophysiological features in several territories. Previous
      reports points at early nonenzymatic glycosylation products (Amadori adducts) as
      mediators of diabetic vascular complications. In the present study, we analysed a
      possible role for Amadori adducts as stimulators of proinflammatory pathways in
      human peritoneal mesothelial cells (HPMCs). Cultured HPMCs isolated from 13
      different patients (mean age 38.7+/-16 years) were exposed to different Amadori
      adducts, that is, highly glycated haemoglobin (10 nM) and glycated bovine serum
      albumin (0.25 mg ml(-1)), as well as to their respective low glycosylation
      controls. Amadori adducts, but not their respective controls, elicited a marked
      increase of NF-kappaB activation, as determined by electromobility shift assays
      and transient transfection experiments. Additionally, Amadori adducts
      significantly increased the production of NF-kappaB-related proinflammatory
      molecules, including cytokines, such as TNF-alpha, IL-1beta or IL-6, and enzymes,
      such as cyclooxygenase-2 and inducible nitric oxide (NO) synthase, this latter
      leading to the release of NO by HPMCs. The effects of Amadori adducts were
      mediated by different reactive oxygen and nitrosative species (e.g. superoxide
      anions, hydroxyl radicals, and peroxynitrite), as they were blunted by
      coincubation with the appropriate scavengers. Furthermore, NO generated upon
      exposure to Amadori adducts further stimulated NF-kappaB activation, either
      directly or after combination with superoxide anions to form peroxynitrite. We
      conclude that Amadori adducts can favour peritoneal inflammation by exacerbating
      changes in NO synthesis pathway and triggering NF-kappaB-related proinflammatory
      signals in human mesothelial cells.

PMID- 15997236
TI  - Selective inhibition of inhibitory kappa B kinase-beta abrogates induction of
      nitric oxide synthase in lipopolysaccharide-stimulated rat aortic smooth muscle
      cells.
AB  - In this study, we utilised a number of adenoviral constructs in order to examine
      the role of intermediates of the NF-kappaB pathway in the regulation of inducible
      nitric oxide synthase (iNOS) induction in rat aortic smooth muscle cells
      (RASMCs). Lipopolysaccharide (LPS) stimulated a significant increase in iNOS
      induction and NF-kappaB DNA binding. These parameters were substantially reduced
      by overexpression of a wild-type Ikappa-Balpha adenoviral construct (Ad.Ikappa
      Balpha), confirming a role for NF-kappaB in iNOS induction. Infection with a
      dominant-negative IKKalpha adenoviral construct (Ad.IKKalpha+/-) did not
      significantly affect iNOS induction, NF-kappaB DNA binding or Ikappa-Balpha loss.
      Infection of RASMCs with adenovirus encoding a dominant-negative IKKbeta
      (Ad.IKKbeta+/-) essentially abolished iNOS induction and activation of the NF
      kappaB pathway. Pretreatment of RASMCs with a novel specific inhibitor of
      IKKbeta, SC-514, significantly reduced iNOS induction, NF-kappaB DNA binding and
      I-kappaBalpha loss in a concentration-dependent manner. In both RASMCs and human
      umbilical vein endothelial cells (HUVECs), infection with Ad.IKKbeta+/- also
      inhibited COX-2 expression in response to LPS. However, Ad.IKKalpha+/- was again
      without effect. These data suggest that IKKbeta plays a predominant, selective
      role in the regulation of NF-kappaB-dependent induction of iNOS in RASMCs.

PMID- 15997237
TI  - Rosiglitazone ameliorates abnormal expression and activity of protein tyrosine
      phosphatase 1B in the skeletal muscle of fat-fed, streptozotocin-treated diabetic
      rats.
AB  - Protein tyrosine phosphatase 1B (PTP1B) acts as a physiological negative
      regulator of insulin signaling by dephosphorylating the activated insulin
      receptor (IR). Here we examine the role of PTP1B in the insulin-sensitizing
      action of rosiglitazone (RSG) in skeletal muscle and liver. Fat-fed,
      streptozotocin-treated rats (10-week-old), an animal model of type II diabetes,
      and age-matched, nondiabetic controls were treated with RSG (10 micromol kg(-1)
      day(-1)) for 2 weeks. After RSG treatment, the diabetic rats showed a significant
      decrease in blood glucose and improved insulin sensitivity. Diabetic rats showed
      significantly increased levels and activities of PTP1B in the skeletal muscle
      (1.6- and 2-fold, respectively) and liver (1.7- and 1.8-fold, respectively), thus
      diminishing insulin signaling in the target tissues. We found that the decreases
      in insulin-stimulated glucose uptake (55%), tyrosine phosphorylation of IRbeta
      subunits (48%), and IR substrate-1 (IRS-1) (39%) in muscles of diabetic rats were
      normalized after RSG treatment. These effects were associated with 34 and 30%
      decreases in increased PTP1B levels and activities, respectively, in skeletal
      muscles of diabetic rats. In contrast, RSG did not affect the increased PTP1B
      levels and activities or the already reduced insulin-stimulated glycogen
      synthesis and tyrosine phosphorylation of IRbeta-subunits and IRS-2 in livers of
      diabetic rats. RSG treatment in normal rats did not significantly change PTP1B
      activities and levels or protein levels of IRbeta, IRS-1, and -2 in diabetic
      rats. These data suggest that RSG enhances insulin activity in skeletal muscle of
      diabetic rats possibly by ameliorating abnormal levels and activities of PTP1B.

PMID- 15997238
TI  - The ICAM-1 antisense oligonucleotide ISIS-3082 prevents the development of
      postoperative ileus in mice.
AB  - Intestinal manipulation (IM) during abdominal surgery triggers the influx of
      inflammatory cells, leading to postoperative ileus. Prevention of this local
      muscle inflammation, using intercellular adhesion molecule-1 (ICAM-1) and
      leukocyte function-associated antigen-1-specific antibodies, has been shown to
      shorten postoperative ileus. However, the therapeutic use of antibodies has
      considerable disadvantages. The aim of the current study was to evaluate the
      effect of ISIS-3082, a mouse-specific ICAM-1 antisense oligonucleotide, on
      postoperative ileus in mice. Mice underwent a laparotomy or a laparotomy combined
      with IM after treatment with ICAM-1 antibodies, 0.1-10 mg kg(-1) ISIS-3082,
      saline or ISIS-8997 (scrambled control antisense oligonucleotides, 1 and 3 mg kg(
      1)). At 24 h after surgery, gastric emptying of a 99mTC labelled semi-liquid meal
      was determined using scintigraphy. Intestinal inflammation was assessed by
      myeloperoxidase (MPO) activity in ileal muscle whole mounts. IM significantly
      reduced gastric emptying compared to laparotomy. Pretreatment with ISIS-3082 (0.1
      1 mg kg(-1)) as well as ICAM-1 antibodies (10 mg kg(-1)), but not ISIS-8997 or
      saline, improved gastric emptying in a dose-dependent manner. This effect
      diminished with higher doses of ISIS-3082 (3-10 mg kg(-1)). Similarly, ISIS-3082
      (0.1-1 mg kg(-1)) and ICAM-1 antibodies, but not ISIS-8997 or higher doses of
      ISIS-3082 (3-10 mg kg(-1)), reduced manipulation-induced inflammation.
      Immunohistochemistry showed reduction of ICAM-1 expression with ISIS-3082 only.
      ISIS-3082 pretreatment prevents postoperative ileus in mice by reduction of
      manipulation-induced local intestinal muscle inflammation. Our data suggest that
      targeting ICAM-1 using antisense oligonucleotides may represent a new therapeutic
      approach to the prevention of postoperative ileus.

PMID- 15997239
TI  - Potential of ketamine and midazolam, individually or in combination, to induce
      apoptotic neurodegeneration in the infant mouse brain.
AB  - Recently, it was reported that anesthetizing infant rats for 6 h with a
      combination of anesthetic drugs (midazolam, nitrous oxide, isoflurane) caused
      widespread apoptotic neurodegeneration in the developing brain, followed by
      lifelong cognitive deficits. It has also been reported that ketamine triggers
      neuroapoptosis in the infant rat brain if administered repeatedly over a period
      of 9 h. The question arises whether less extreme exposure to anesthetic drugs can
      also trigger neuroapoptosis in the developing brain. To address this question we
      administered ketamine, midazolam or ketamine plus midazolam subcutaneously at
      various doses to infant mice and evaluated the rate of neuroapoptosis in various
      brain regions following either saline or these various drug treatments. Each drug
      was administered as a single one-time injection in a dose range that would be
      considered subanesthetic, and the brains were evaluated by unbiased stereology
      methods 5 h following drug treatment. Neuroapoptosis was detected by
      immunohistochemical staining for activated caspase-3. It was found that either
      ketamine or midazolam caused a dose-dependent, statistically significant increase
      in the rate of neuroapoptosis, and the two drugs combined caused a greater
      increase than either drug alone. The apoptotic nature of the neurodegenerative
      reaction was confirmed by electron microscopy. We conclude that relatively mild
      exposure to ketamine, midazolam or a combination of these drugs can trigger
      apoptotic neurodegeneration in the developing mouse brain.

PMID- 15997241
TI  - Association study between chromosome 10q26.11 and obesity among Swedish men.
AB  - OBJECTIVE: Proximal chromosome 10q26 was recently linked to waist/hip ratio in
      European and African-American families. The objective was to investigate whether
      genomic variation in chromosome 10q26.11 reflects variation in obesity-related
      clinical parameters in a Swedish population. DESIGN: Genetic association study of
      single-nucleotide polymorphisms (SNPs) in chromosome 10q26.11 and obesity-related
      clinical parameters was performed. Obesity was defined as body mass index (BMI) >
      or = 30 kg/m2. SUBJECTS: Swedish Caucasians comprising 276 obese and 480 nonobese
      men, 313 obese and 494 nonobese women, 177 obese and 163 nonobese patients with
      type 2 diabetes mellitus (T2DM), and 106 obese and 201 nonobese subjects with
      impaired glucose tolerance (IGT) patients. MEASUREMENTS: Genotypes of 11 SNPs at
      chromosome 10q26.11, and various obesity-related clinical parameters. RESULTS:
      Homozygosity of a common haplotype constructed by three SNPs, rs2185937, rs1797
      and hCV1402327, covering an interval of 2.7 kb, was suggested to confer an
      increased risk for obesity of 1.5 among men (P = 0.043). The C allele frequency
      and homozygous genotype frequency of the rs1797 tended to be higher among obese
      compared to among nonobese men (P = 0.017 and 0.020, respectively). The
      distribution of BMI and diastolic blood pressure was higher among those with the
      C/C genotype (P = 0.022 and 0.0061, respectively). The obese and the nonobese
      groups were homogeneous over BMI subgroups with regard to rs1797 risk genotype
      distribution. There was no tendency for association between rs1797 and obesity
      among neither women nor T2DM nor IGT patients. CONCLUSION: We show support for
      association between proximal chromosome 10q26.11 and obesity among Swedish men
      but not women through the analysis of a haplotype encompassing 2.7 kb.

PMID- 15997242
TI  - Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of
      human visceral adipose tissue.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in
      monocyte recruitment during inflammation whose plasma level is elevated in
      obesity. OBJECTIVE: The present studies were designed to examine the release of
      MCP-1 in primary culture by explants of visceral adipose tissue from morbidly
      obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was
      derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose
      tissue explants was upregulated almost five-fold between 3 and 48 h of
      incubation. Approximately half of this upregulation was due to the release of
      endogenous tumor necrosis factor alpha (TNFalpha) and IL-1beta based on the
      ability of a combination of a soluble TNFalpha receptor (etanercept) and a
      blocking antibody against IL-1beta to reduce MCP-1 release. The release of MCP-1
      over 48 h was unaffected by insulin or dexamethasone but significantly reduced by
      the combination of both agents. MCP-1 release was reduced by 60% in the presence
      of an inhibitor of the nuclear factor kappaB (NF-kappaB) pathway. There were no
      significant effects of inhibitors of p44/42 mitogen-activated protein kinase
      (ERK), Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38
      MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the
      presence of inhibitors of both the p38 MAPK and NF-kappaB pathways was greater
      than that seen with only the NF-kappaB inhibitor. DISCUSSION: The present data
      shows that MCP-1 formation is upregulated over a 48-h incubation of primary
      explants of visceral adipose tissue. Half of this upregulation is dependent upon
      endogenous TNFalpha and Il-1beta and involves the p38 MAPK and NF-kappaB
      pathways.

PMID- 15997243
TI  - Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate
      hyperplasia or apoptosis.
AB  - OBJECTIVE: There is an increased incidence of renal glomerulosclerosis in obese
      individuals. One of the major structural changes observed in nephropathy is the
      increase in kidney size, which may occur due to hypertrophy or changes in the
      rate of hyperplasia or apoptosis. Here we investigated whether leptin, the
      product of the obese (ob) gene which is found at high plasma levels in obese and
      diabetic individuals, alters any of these parameters. RESULTS: We show that
      leptin increased hypertrophy of these cells. This was indicated by an
      approximately 33% increase in cell size and 40% increase in leucine
      incorporation. Furthermore, we show that the hypertrophic effect of leptin was
      mediated via PI 3-kinase and ERK1/2 by using the inhibitors LY294002 and PD98059,
      respectively. We also confirm that leptin activates both PI 3-kinase and ERK1/2
      in these cells. We show that hyperplasia was not affected by leptin by measuring
      rat glomerular mesangial cell number and by assessing bromodeoxyuridine uptake.
      Leptin also did not alter caspase 3-like activity under control conditions or
      upon induction of apoptosis by ultraviolet light, suggesting that apoptosis was
      not regulated by leptin in these cells. CONCLUSION: Our results show that leptin
      induced glomerular mesangial cell hypertrophy via PI 3-kinase and ERK1/2, and
      that hyperplasia and apoptosis were not altered by leptin. The hypertrophic
      effect of leptin may play a role in the pathophysiology of nephropathy associated
      with obesity.

PMID- 15997244
TI  - Smoking status, cigarettes per day, and their relationship to overweight and
      obesity among former and current smokers in a national adult general population
      sample.
AB  - BACKGROUND: Weight gain after smoking cessation is perceived to be a barrier
      against quitting smoking. The goal was to analyze overweight and obesity
      depending on smoking status and number of cigarettes per day (cpd) among former
      and current smokers. METHODS: The sample included 7124 residents of Germany aged
      18-79 y from a national health examination survey (participation rate: 61.4%).
      Body weight and height were objectively measured; smoking status and cpd were
      assessed by a questionnaire administered in a health examination center. RESULTS:
      The number of cpd was positively related to being overweight and more so to
      obesity among former smoking men, but not women. The results were adjusted for
      age, school education, exercise and alcohol consumption. Men who formerly had
      smoked more than 30 cpd had an adjusted odds ratio (OR) of 5.0 for obesity
      compared to men who had never smoked. CONCLUSION: With an increasing number of
      cpd more psychological and physiological processes of compensation of nicotine
      supply after smoking cessation may be expected. Male smokers should be provided
      with information on how to prevent weight gain after smoking cessation. To foster
      smoking cessation, female smokers should be informed that women who stop smoking
      manage to have no increase in the rates of overweight or obesity when considered
      at the general population level.

PMID- 15997245
TI  - Circulating soluble leptin receptor, leptin, and insulin resistance before and
      after weight loss in obese children.
AB  - OBJECTIVE: To study the relationships between leptin, soluble leptin receptor
      (sOB-R), and insulin resistance in obese children before and after weight
      reduction. METHODS: We determined fasting serum leptin, sOB-R, and insulin
      resistance index (Homeostasis model assessment (HOMA)) in 36 obese children at
      baseline and 1 y later and compared them to 72 lean children matched for age,
      gender, and pubertal stage. The changes of leptin (Deltaleptin) and sOB-R
      (DeltasOB-R) over the 1 y period were correlated to the changes of HOMA
      (DeltaHOMA), the changes of weight status, and the changes of percentage body fat
      (Delta%BF) based on skinfold measurements. Multiple linear regression analyses
      were conducted for the dependent variables Deltaleptin and DeltasOB-R, including
      DeltaBMI and DeltaHOMA as independent variables adjusted for age, gender, and
      pubertal stage. Changes of leptin and sOB-R levels were analyzed in 11 obese
      children after they had lost weight substantially (decrease SDS-BMI>0.5) and
      compared to 11 obese children without substantial weight loss matched for age,
      gender, and pubertal stage. RESULTS: Obese children showed significantly
      (P<0.001) higher leptin and lower sOB-R levels. Deltaleptin correlated
      significantly to DeltaSDS-BMI (r=0.28, P<0.05), Delta%BF (r=0.44, P<0.05), and
      DeltaHOMA (r=0.42, P<0.01), while DeltasOB-R correlated significantly to DeltaSDS
      BMI (r=-0.42, P<0.01) and Delta%BF (r=-0.47, P<0.01), but not to DeltaHOMA. In
      contrast to DeltasOB-R, Deltaleptin correlated significantly to DeltaHOMA
      (P=0.02) in multiple linear regression analysis. Substantial weight loss led to a
      significant increase in sOB-R (P=0.02) and to a decrease in HOMA (P=0.02). In
      children without substantial weight loss, there were no changes in sOB-R, while
      HOMA (P=0.04) and leptin (P=0.02) increased significantly. CONCLUSIONS: The
      decrease of sOB-R and the increase of leptin levels in obese children normalized
      after weight loss. Therefore, these changes are consequences rather than the
      cause of overweight. In contrast to sOB-R, leptin levels are associated with
      insulin resistance.

PMID- 15997246
TI  - Genetic variation in leptin receptor gene is associated with type 2 diabetes and
      body weight: The Finnish Diabetes Prevention Study.
AB  - OBJECTIVE: Genetic variation in leptin receptor (LEPR) gene has been reported to
      associate with insulin and glucose metabolism and adiposity in different study
      settings and various populations. We wanted to evaluate the association between
      LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with
      impaired glucose tolerance (IGT). METHODS: We investigated the associations of
      the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the
      conversion to type 2 diabetes and the changes in body weight in 507 individuals
      with IGT participating in the Finnish Diabetes Prevention Study. Participants
      were randomized to either an intensive diet and exercise intervention group or a
      control group. RESULTS: After 3 years, the odds ratio for the development of type
      2 diabetes in individuals in the control group with the Lys109Lys genotype was
      2.38-fold higher than in individuals with other genotype combinations (P=0.016).
      Irrespective of group individuals with the Gln223Gln genotype had higher
      conversion to type 2 diabetes (OR 2.01 (95% CI 1.03-3.93)) than the Arg223 allele
      carriers (P=0.042). The risk was more pronounced in the control group than in the
      intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly
      higher body weight throughout the study than those with the insertion allele
      (P=0.020), although no difference in weight change was observed. CONCLUSION: Two
      polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin
      receptor predicted the conversion to type 2 diabetes in high-risk individuals
      with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body
      weight.

PMID- 15997247
TI  - Weight, fat mass, and central distribution of fat increase when women use depot
      medroxyprogesterone acetate for contraception.
AB  - OBJECTIVE: To compare longitudinal changes in weight, body fat, and ratio of
      central to peripheral fat mass among first-time depot-medroxyprogesterone acetate
      (DMPA) users to women using no hormonal contraception, and to evaluate user
      characteristics associated with that change. DESIGN: Prospective longitudinal
      study. SUBJECTS: Healthy women, aged 18-35 y, using DMPA for contraception
      (n=178) and women using no hormonal contraception (n=145). MEASUREMENTS: Weight,
      body fat, and the central distribution of fat, measured at 3-month intervals for
      30 months, by electronic scale and dual-energy X-ray absorptiometry (DEXA). The
      ratio of central to peripheral distribution of body fat was computed by dividing
      the body fat in the conventional DEXA trunk region of interest (ROI) by the ROI's
      that encompass the arms, hips and legs. RESULTS: Women using DMPA had a
      significantly greater increase in all measures of fatness than women using no
      hormonal method of contraception (P<0.03). The observed weight of DMPA users
      increased from a mean of 69.4 kg (s.d.=16.9) at baseline to 75.5 kg (s.d.=25.0)
      at 30 months; an increase of 6.1 kg (8.8.%). Fat mass increased from a mean of
      25.3 kg (s.d.=12.6 kg) at baseline to 31.4 kg (s.d.=17.8); an increase of 6.1 kg
      (23.6%) in DMPA users. The ratio of central to peripheral fat mass in DMPA users
      changed from 0.95 (s.d.=0.155) at baseline to 1.01(s.d.=0.198) at 30 months. In
      contrast, weight, fat mass and the ratio of central to peripheral fat mass of
      control participants remained virtually unchanged over the same time period.
      Women with higher baseline physical activity levels had a smaller increase in
      body fat (P=0.003) and the fat ratio (P=0.03), but not weight (P=0.48). No other
      user characteristics including, smoking, past oral contraceptive use or previous
      pregnancies predicted change in level of fatness. CONCLUSIONS: This study has
      demonstrated a change in body composition toward greater fatness and toward a
      central redistribution of fat among DMPA users as compared to controls and
      provides important information to be used when counseling women regarding
      contraceptive methods. Given the potential long-term implication of these
      changes, further study is recommended to determine whether the gains in fatness
      are reversed following DMPA discontinuation and to examine the role of progestins
      in the development and maintenance of obesity.

PMID- 15997248
TI  - Obesity and overweight in relation to organ-specific cancer mortality in London
      (UK): findings from the original Whitehall study.
AB  - OBJECTIVE: To examine the relation of obesity and overweight with organ-specific
      cancer mortality. METHODS: In the Whitehall prospective cohort study of London
      based government employees, 18 403 middle-age men participated in a medical
      examination between 1967 and 1970. Subjects were followed up for cause-specific
      mortality for up to 35 y (median: interquartile range (25th-75th centile); 28.1
      y: 18.6-33.8). RESULTS: There were over 3000 cancer deaths in this cohort. There
      was a raised risk of mortality from carcinoma of the rectum, bladder, colon, and
      liver, and for lymphoma in obese or overweight men following adjustment for range
      of covariates, which included socioeconomic position and physical activity. These
      relationships held after exclusion of deaths occurring in the first 20 y of
      follow-up. CONCLUSION: Avoidance of obesity and overweight in adult life may
      reduce the risk of developing some cancers.

PMID- 15997249
TI  - Is the insulin resistance syndrome the price to be paid to achieve body weight
      stability?
AB  - The insulin resistance syndrome represents a metabolic state in which
      hyperinsulinemia and/or insulin resistance constitute the platform underlying the
      development of metabolic complications and related diseases such as diabetes and
      coronary heart disease. As described in this paper, these insulin-related changes
      are also involved in the regulation of energy balance and contribute to the
      recovery of body weight stability in a context of long-term positive energy
      balance. Under conditions of negative energy balance such as obesity treatment,
      this connection has a high clinical relevance. In this regard, relevant
      literature as well as the reanalysis of previously published data suggest that
      the beneficial effect of weight loss on insulin-related changes in glycemia
      cannot be disassociated from the relationship between changes in plasma insulin
      and those in resting energy expenditure. In clinical terms, this suggests that
      the beneficial effect of weight loss on components of the insulin resistance
      syndrome could be related to the development of a state of physiological
      vulnerability that complicates the control of body weight. This poses a major
      challenge to health professionals who then have to manage obesity treatment as
      the search for a compromise between the beneficial and potentially detrimental
      effects of weight loss on insulinemia and insulin sensitivity. This also
      reinforces the relevance to adhere to healthy diet and physical activity habits
      in order to maintain body weight stability rather than relying on the overuse of
      regulatory systems soliciting the effects of hyperinsulinemia on the control of
      energy intake and expenditure.

PMID- 15997250
TI  - Systematic review of long-term weight loss studies in obese adults: clinical
      significance and applicability to clinical practice.
AB  - BACKGROUND: Obesity is a common health problem that requires a long-term care
      approach. We systematically reviewed long-term (> or =2 y) studies investigating
      dietary/lifestyle, pharmacologic, and surgical weight loss methods to assess (1)
      weight loss efficacy, defined by absolute weight loss and the proportion of
      subjects with > or =5% weight loss, (2) effects of weight loss on cardiovascular
      risk factors, and (3) applicability of findings from studies to everyday clinical
      practice. METHODS: The MEDLINE, HealthSTAR, and the Cochrane Controlled Trials
      databases were searched for studies investigating the long-term efficacy of
      weight loss methods in overweight and obese adults. Data were extracted for (i)
      weight loss after 1 y (pharmacologic studies only), 2 y, 3 y, and 4 y, (ii)
      proportion of subjects with > or =5% weight loss at the end of follow-up, and
      (iii) changes (end-of follow-up minus baseline values) in blood lipids, fasting
      blood glucose, and systolic and diastolic blood pressure. RESULTS:
      Dietary/lifestyle therapy provides <5 kg weight loss after 2-4 y, pharmacologic
      therapy provides 5-10 kg weight loss after 1-2 y, and surgical therapy provides
      25-75 kg weight loss after 2-4 y. Weight loss of > or =5% baseline weight is not
      consistently associated with improvements in cardiovascular risk factors and
      these benefits appear to be intervention specific and occur mainly in people with
      concomitant cardiovascular risk factors. Weight loss studies have methodologic
      limitations that restrict the applicability of findings to unselected obese
      people assessed in everyday clinical practice. These limitations include an
      inadequate study duration, large proportions of subjects lost to follow-up, a
      lack of an appropriate usual care group, and a lack of reporting of outcomes in
      high-risk subgroups. CONCLUSIONS: Dietary/lifestyle and pharmacologic weight loss
      interventions provide modest weight loss, and may improve markers of
      cardiovascular risk factors although these benefits occur mainly in patients with
      cardiovascular risks. Studies investigating weight loss have methodologic
      limitations that restrict the applicability of findings to obese patients
      assessed in clinical practice.

PMID- 15997251
TI  - Adult onset otitis media with effusion in Lagos.
AB  - BACKGROUND/AIM: The documented reports on adult onset OME is scanty world wide,
      this study was prompted by the increasing trend of OME in our adult patients with
      the aim of determining the prevalence, predisposing factors and treatment outcome
      of the disease. PATIENTS AND METHODS: A prospective study was carried out over a
      two year period at the Otolaryngology Clinic of Lagos University Teaching
      Hospital Lagos Nigeria, on 195 patients referred to the clinic with provisional
      diagnosis of OME. The patients had clinical evaluation, pure tone audiometry,
      tympanometry while a few had fibre optic nasopharyngoscopy and biopsy done.
      RESULTS: A hospital based prevalence of 2.6% was recorded in the Otolaryngology
      clinic during the study period, with infective and allergic sinusitis as the
      major predisposing factors to OME in adult patients. Majority 58 (92.06%)
      patients were treated conservatively and recurrence was seen in 8 (12.7%) of the
      patients without any untoward effects. OME, though recognised as a childhood
      disease may be as prevalent in adult as in childhood but with less complication.
      CONCLUSION: OME as a single clinical feature or in association with allergy or
      sinusitis is most unlikely to habour NPC therefore nasopharyngoscopy and biopsy
      are likely to give a low yield of positive biopsy in isolated OME in adult and
      the cost implication of this must be borne in mind.

PMID- 15997252
TI  - Alcohol use and abuse among medical and surgical in-patients in a general
      hospital.
AB  - OBJECTIVE: Non-recognition of alcohol problems in medical and surgical patients
      may have adverse consequences. This may be minimised by having a high index of
      suspicion and the use of screening instruments. PATIENTS AND METHODS: Items from
      two alcohol abuse screening instruments (CAGE and Patient Health Questionnaire)
      were administered on medical and surgical in-patients in a general hospital
      during a one-year period, to determine the prevalence of alcohol use and abuse.
      RESULTS: The prevalence of alcohol use was 49.8% and for alcohol abuse 14.8%.
      Paternal alcohol use and cigarette smoking were found to be good indicators of
      alcohol abuse. CONCLUSION: Detailed inquiry about alcohol use, looking for
      indices of cigarette smoking and routine use of screening instruments should
      assist in discovering many patients with alcohol abuse who probably would have
      denied having the problem.

PMID- 15997253
TI  - Effect of changes in plasma vitamin E level of vascular responses and lipid
      peroxidation in sickle cell anaemia subjects.
AB  - The effect of vitamin E supplementation (300 mg/day for 6 weeks) on blood
      pressure, forearm blood flow, forearm vascular resistance, plasma vitamin E level
      and lipid peroxidation status was investigated in adult sickle cell anaemia
      subjects. Ten adults whose ages ranged from 19.0 to 25.0 years (mean 22.8+/-0.8
      years) were studied. Vitamin E supplementation had little or no effect on
      arterial blood pressure but significantly increased forearm blood flow (p<0.001)
      and plasma vitamin E level (p<0.001). However it significantly decreased lipid
      peroxidation status (p<0.001) and forearm vascular resistance (p<0.001). The
      change in plasma vitamin E concentration correlated negatively with change in
      lipid peroxidation status (r=-0.8; p=0.003). However, change in plasma vitamin E
      concentration correlated positively with change in forearm blood flow (r=0.8;
      p=0.006). There was an inverse correlation between change in plasma lipid
      peroxidation and change in forearm blood flow (r=-0.7; p=0.03). The study
      therefore shows that in sickle cell anaemia subjects, vitamin E supplementation
      increases forearm blood flow and reduces forearm vascular resistance and lipid
      peroxidation. The increase in forearm blood flow correlates inversely with the
      reduction in lipid peroxidation. This suggests that in sickle cell anaemia
      subjects, vitamin E supplementation could cause an increase in forearm blood flow
      by decreasing plasma lipid peroxidation level.

PMID- 15997254
TI  - Serum lipids in women on oral contraceptives in Zaria-Nigeria.
AB  - AIM: To compare the serum lipid levels of women on two different types of oral
      contraceptives, norethindrone 0.5 mg/ethinyl oestradiol 0.035 mg and norgesterol
      0.5 mg/ethinyl oestradiol 0.03 mg. METHOD: Serum total cholesterol, HDL
      cholesterol, LDL-cholesterol and triglyceride levels were estimated in two groups
      (A&B) of women. Group A were 35 women who had been on norethindrone 0.5
      mg/ethinyl oestradiol 0.035 mg for over one year, while the group B were 35 women
      on norgesterol 0.5 mg/ethinyl oestradiol 0.03 mg for three months. Thirty five
      healthy, age- matched women not on oral contraceptive agent were used as
      controls. RESULTS: Significantly higher levels of serum total cholesterol and
      triglycerides were found in the group A women compared to the group B women. The
      mean HDL-cholesterol level was significantly higher in the group B women in the
      2nd and 3rd months of therapy than in the controls. The LDL-cholesterol levels
      were statistically similar in the two groups of contraceptive users and the
      controls. The results obtained were within the reference interval established in
      our laboratory. CONCLUSION: The oral contraceptive containing norgesterol 0.5
      mg/ethinyl oestradiol 0.03 mg was found to be better as it increased the levels
      of HDL-cholesterol more than the other lipids. It is not known if this finding
      will persist on long-term use of the oral contraceptive.

PMID- 15997255
TI  - Aetiology of catheter-associated bacteriuria in Lagos University Teaching
      Hospital.
AB  - A prospective study to determine the causative agents of catheter-related
      bacteriuria was carried out on 99 patients with median age of 55 years, on
      admission in the Oncology, Paediatric Surgery and Obstetric and Gynaecology wards
      of the Lagos University Teaching Hospital. There was significant bacteriuria in
      seventy-one (72%) of the 99 urine samples. All catheter urine samples were
      contaminated by day 5 Gram-negative bacilli were predominant (89.3%) of which
      Pseudomonas aeruginosa (26.2%) was the most common, while Escherichia coli and
      Enterobacter aerogenes accounted for 15.5% each, closely followed by Proteus
      mirabilis (14.3%) and Klebsiella pneumoniae (9.5%). The Gram positive isolates
      Enterococcus faecalis (8.3%) and Staphylococcus saprophyticus (2.4%) made up only
      10.7% of isolates. Most of the isolates from catheterised patients were resistant
      to the common antibiotics such as ampicillin, cotrimoxazole, gentamicin and
      ceftriaxone with high susceptibility to ofloxacin and ceftazidime though the
      isolates of Enterococcus faecalis was also resistant to ofloxacin. However,
      isolates of S. saprophyticus were still susceptible to the penicillins and
      tetracycline.

PMID- 15997256
TI  - An assessment of food hygiene among food handlers in a Nigerian university
      campus.
AB  - INTRODUCTION: Food handlers play a major role in ensuring food safety throughout
      the chain of producing, processing, storage and preparation. Mishandling and
      disregard for hygiene measures on their part may result in food contamination and
      its attendant consequences. OBJECTIVES: This study was designed to assess the
      knowledge and practice of food hygiene by food handlers in a Nigerian University
      Campus. METHODOLOGY: A descriptive, cross-sectional study was carried out on
      randomly selected food handlers operating on the campus. A total of 102
      respondents were interviewed and inspected using a structural questionnaire
      administered by researchers. RESULTS: Ninety (88.2%) of the respondents were
      female, and there was a predominantly poor level knowledge of food hygiene. The
      practice of storing and reheating leftovers was low and agreed to by 15 (14.7%)
      of the respondents; there was a very low frequency of hand washing. Inspection of
      food handlers showed a low level of personal hygiene. Only 31 (30.4%) had had pre
      employment medical examination and only 49 (48%) had received any form of health
      education. CONCLUSION: This study has revealed a poor knowledge and practice of
      food hygiene among food handlers providing food for undergraduates in a Nigerian
      University. It is recommended that a massive health education campaign directed
      at both the public and food handlers be embarked on, to enable people take
      necessary steps to prevent food borne diseases.

PMID- 15997257
TI  - Comparative study of the therapeutic effect of a systemic analgesic and
      transcutaneous electrical nerve stimulation (TENS) on post-IMF trismus and pain
      in Nigerian patients.
AB  - OBJECTIVES: To compare the therapeutic effect of paracetamol and Transcutaneous
      Electrical Nerve Stimulation (TENS), on post-Intermaxillary Fixation (IMF)
      trismus, and pain in some Nigerian patients. PATIENTS AND METHODS: Twenty
      patients treated for mandibular fractures with IMF were randomly selected into
      two groups of ten patients each. After the release of IMF, they were started on
      jaw exercises with the aid of wooden spatulae to overcome trismus due to muscle
      spasm. Patients in Group I underwent jaw exercises before and after TENS therapy
      which lasted for 30 minutes while those in Group II had jaw exercises before and
      30 minutes after ingestion of 100 mg of paracetamol. Their inter-incisal
      distances were recorded pre and post intervention. RESULTS: Analysis of the data
      showed that for both therapeutic interventions, there was an appreciable gain in
      mouth-opening which was more prominent for patients with unusual difficulty in
      mouth-opening initially. However, a comparison between the mean improvements
      produced by TENS and analgesic revealed no significant difference between the two
      groups. CONCLUSION: Both the TENS therapy and paracetamol provided similarly
      appreciable differences in inter-incisal distances (mouth-opening) after their
      applications.

PMID- 15997258
TI  - The influence of foetal haemoglobin on the frequency of vaso-occlusive crisis in
      sickle cell anaemia patients.
AB  - OBJECTIVE: Several biological and environmental factors are presumed to account
      for the morbidity pattern in patients with sickle cell anaemia. Foetal
      haemoglobin is one of the biological factors thought to decrease morbidity in
      these patients. We studied the relationship between the foetal haemoglobin levels
      and vaso-occlusive crisis (VOC) as a measure of the morbidity pattern in this
      category of patients. RESULTS: The mean foetal haemoglobin level was 6.4+0.40%
      (SEM). Vaso-occlusive crisis was more common at lower levels of foetal
      haemoglobin particularly when lower than 12% (P=0.01). There was a negative
      correlation between foetal haemoglobin and vaso-occlusive crisis (r=0.561). These
      variables were also associated in linear regression and both showed statistical
      significance (p=0.001). CONCLUSION: We conclude that higher levels of foetal
      haemoglobin positively influence the occurrence of vaso-occlusive crisis in
      sickle cell anaemia patients.

PMID- 15997259
TI  - Radiological assessment of femoral neck-shaft and anteversion angles in adult
      Nigerian HIPS.
AB  - A trigonometric calculation of projected femoral neck shaft or cetrum-collum
      diaphysis angle (CCD angle) and anteversion angle (AT angle) were assessed in
      normal adult Nigerian hips using the standardised biplane radiography described
      by Muller and Rippstein. A mean CCD angle and AT angle of 121 degrees+/-6 (SD)
      and 28 degrees+/-5 (SD) respectively were obtained in the 116 Nigerian adult hips
      assessed. The values obtained were inconsistent with quoted reference ranges of
      130 degrees+/-7 and 10 degrees+/-7 respectively. There was however no significant
      difference between the female and male CCD and AT angles.

PMID- 15997260
TI  - Changes in erythrocytes following supplementation with alpha-tocopherol in
      children suffering from sickle cell anaemia.
AB  - INTRODUCTION: Low plasma vitamin E level in children with sickle cell anaemia has
      been related to elevated level of irreversibly sickled cells which has been
      implicated in the pathogenesis of painful crisis. In adult patients
      supplementation with alpha-tocopherol has been shown to reduce irreversibly
      sickled cell count. In-addition, vitamin E supplementation increases resting
      forearm blood flow and reduces forearm vascular resistance in adult sickle cell
      anaemia sufferers. AIM: The aim of the study was to examine the effects of
      supplementation with alpha-tocopherol on arterial blood pressure, some
      haematological parameters and osmotic fragility in children suffering from sickle
      cell anaemia. METHODOLOGY: The effects of supplementation with alpha-tocopherol
      (100 mg. per day for 6 weeks) on packed cell volume (PCV) haemoglobin
      concentration ([Hb]), mean corpuscular haemoglobin concentration (MCHC), per cent
      foetal haemoglobin (% HbF), per cent irreversibly sickled cells (%ISC),
      erythrocyte osmotic fragility and blood pressure have been assessed in ten (10)
      children suffering from sickle cell anaemia. Their ages ranged from 4.0 to 10.0
      years. RESULTS: Supplementation with alpha-tocopherol significantly increased
      packed cell volume (p<0.001), haemoglobin concentration (p<0.01) and per cent
      foetal haemoglobin (p<0.001), but significantly reduced mean corpuscular
      haemoglobin concentration (p<0.01) and per cent irreversibly sickled cells
      (p<0.001). alpha-Tocopherol also increased the resistance of the cells to lysis.
      Supplementation with alpha-tocopherol had little or no effect on arterial blood
      pressure. CONCLUSION: This study shows that short-term supplementation with alpha
      tocopherol may be beneficial to the paediatric sickle cell sufferer.

PMID- 15997261
TI  - Parental awareness of emergency management of avulsion of permanent teeth of
      children in Lagos, Nigeria.
AB  - BACKGROUND/OBJECTIVES: Traumatic injuries in children and adolescents affecting
      both the primary and permanent dentitions and their supporting structures are a
      common problem seen in children. Avulsion of permanent teeth in children
      resulting from trauma is an emergency in children. The prognosis of avulsed teeth
      depends on prompt and appropriate treatment, which often relies on lay people
      such as the children's parents and their schoolteachers who are present at the
      site of the accident, prior to the initial professional dental contact. Knowledge
      of parents on the emergency management is thus surveyed. METHOD: A 13- stemmed
      questionnaire comprising questions on demographic data, attitude and knowledge
      was distributed to parents who have accompanied their children (patients) to the
      Orthodontic/Paedodontic Clinics of Lagos University Teaching Hospital (LUTH) for
      treatment over a 12-week period from October- December 2002. RESULT: A total of
      ninety parents were studied. Over 90% of the parents felt they should seek
      professional help urgently following an avulsion injury, but their knowledge of
      transport medium for the tooth was poor. Only 1.1 per cent and 3.3 per cent knew
      that milk was the medium of choice for washing and transporting an avulsed tooth
      respectively. 91.1% of parents surveyed had never received advice on what to do
      in the event of an accident where a permanent tooth was avulsed. CONCLUSION:
      There is a need for educational campaigns aimed at parents to increase their
      knowledge of the emergency procedures required when the tooth is avulsed.

PMID- 15997262
TI  - Occlusal features of sickle cell anaemia patients in Lagos, Nigeria.
AB  - One hundred and four sickle cell anaemia patients aged 10-45 years and attending
      the out patients' clinic of the Lagos University Teaching Hospital as part of a
      routine check-up were seen. They were in a steady state of health. By means of a
      structured questionnaire the Biodata of each consecutive eligible patient was
      obtained and physical examination was carried out. Oral examination was done with
      emphasis on occlusal variables including Angle's Classification of occlusion,
      overjet, overbite, tooth: bone ratio, lip competence and skeletal pattern.
      Results showed that the majority of the patients 92 (88.5%) seen presented with
      Angle's Class 1 malocclusion. Increased overjet was observed in 50 (48.2%) of the
      sample population while an overbite depth of 2 was most frequently seen in these
      patients. Spacing in the anterior segment of the upper and lower arches was a
      fairly common occurrence, occurring in 51 (49.0%) and 39 (30.8%) of the patients
      seen respectively. Normal dental base relationship (Skeletal 1) was observed in
      72 (69.2%) while lip incompetence was seen in 41 (39.4%) of the patients
      examined. Occlusal anomalies vary from mild to severe and may be attributable to
      hyperplastic maxillary bone and the resultant skeletal discrepancy.

PMID- 15997263
TI  - Malignant melanoma: a review.
AB  - The incidence of malignant melanoma the most malignant of all skin neoplasms, has
      doubled within the last 10 years. Exposure to high intensity sunlight, racial
      susceptibility, hormonal status, age, environmental factors as well as injury
      have all been shown to play a role individually or synergistically in the
      activation of the melanocytic oncogen. Controversies still exist in which factors
      actually determine prognosis, in patients with advanced malignant melanoma.
      Management has remained even more controversial, with surgical excision, with or
      without lymphadenectomy, radiotherapy, chemotherapy, laser therapy and more
      recently immunotherapy and intra-arterial neutron thermal capture therapy, having
      their proponents and opponents.

PMID- 15997264
TI  - Adenomatoid odontogenic tumour: a clinico-pathological analysis and melanin
      pigmentation study of 31 Nigerian cases.
AB  - AIM: Clinicopathological analysis and melanin pigmentation occurrence in
      adenomatoid odontogenic tumour (AOT) diagnosed and managed at the Lagos
      University Teaching Hospital during a 29- year period. METHODS: Records of 31
      cases were reviewed and standard epidemiological data were obtained. Haematoxylin
      and eosin stained slides of the cases were retrieved and reevaluated for
      reconfirmation of diagnosis. Celloidinised paraffin sections of all cases were
      subjected to Fontana Masson stain and melanin bleach to assess presence of
      melanin pigment. RESULTS: AOT is an uncommon type of odontogenic tumour that is
      commoner in younger age group (8-35 years) with site predilection for the
      anterior maxilla (64.5%). Occurrence of melanin pigment in AOT was very rare as
      there was positive melanin pigmentation in only one case in spite of the fact
      that the study was carried out in a predominantly Black population. CONCLUSION:
      Pattern of occurrence of AOT observed in this Lagos series is similar to previous
      studies in the scientific literature. Melanin pigmentation is rarely demonstrated
      in AOT even in a predominantly Black population.

PMID- 15997265
TI  - Point of care testing: a delight or a dilemma in the developing world?: an
      overview.
AB  - OBJECTIVES: This is to highlight the use of POCT especially by the untrained
      laboratorians, and its disadvantages and advantages. PATIENTS AND METHODS: The
      results of urinalysis carried out in Antenatal Clinic and Central Chemical
      Pathology laboratory for a two-year period were analysed to determine how the
      results were interpreted, whether there were further request(s) and how relevant
      they were. The results of 56 out of 303 oral glucose tolerance tests carried out
      because of positive glucose in urine (glycosuria) were reviewed. Similarly the
      results of 176 pregnant women who had proteinuria on urinalysis in Antenatal
      Clinic and 92 patients who had positive bilirubin-diglucuronide in their urine
      (bilirubinuria) were also reviewed. RESULTS: The result shows that only 18 out of
      the 56 patients who had OGTT based on positive glucose in their urine had
      glycosuria on fasting urine sample on the OGTT day. 4 of them had gestational
      diabetes mellitus, 2 were diabetic before conception 5 had impaired glucose
      tolerance, while 7 had renal glycosuria. Thirty-eight results were false
      positives with repeat urinalysis and OGTT. Also out of the 176 pregnant women who
      had proteinuria on urinalysis only 57(32.4%) were confirmed on repeat urinalysis
      and/or 24 hr urinary protein quantification, 51 became negative after successful
      treatment of their UTI, while 68(38.6%) were false positives. Similarly out of 92
      patients who had bilirubinuria only 23 showed abnormalities suggestive of some
      degree of liver disease. CONCLUSION: Results obtained on POCT must be validated
      in the central laboratory.

PMID- 15997266
TI  - Vaginal injuries during coitus in Calabar: a 10-year review.
AB  - Injuries during coitus could result in considerable morbidity and mortality in
      women. Identifying their pattern of presentation and predisposing factors will
      aid in their prevention. STUDY DESIGN AND SETTING: A descriptive study of
      patients with coital injuries seen in the University of Calabar Teaching Hospital
      (U.C.T.H) Calabar, between 1991 and 2000, with data obtained from case records.
      RESULTS: Coital injuries constituted 0.7/1000 gynaecological emergencies. Rape
      (68.0%) was the commonest aetiological factor. It was more common in nulliparous
      patients (88.0%) and toddlers and teenagers formed the age group most affected.
      The lower vagina was the most common site of injury (44.0%). Vaginal bleeding was
      the commonest mode of presentation and hypovolaemic shock, the most common
      complication. CONCLUSION: Rape is the commonest cause of coital injury in
      Calabar. Coital injuries should be considered as a differential diagnosis in all
      cases of abnormal vaginal bleeding particularly in children.

PMID- 15997267
TI  - Predictors of colorectal cancer screening: a comparison of men and women.
AB  - BACKGROUND: New Canadian guidelines recommend screening average-risk adults to
      reduce mortality from colorectal cancer, the second most common cause of cancer
      death among Canadians. The present study examined the self-reported prevalence of
      colorectal cancer testing and sex-specific predictors of having had a fecal
      occult blood (FOB) test for screening, among a cohort of Alberta residents aged
      50 to 69 years. METHODS: Subjects (n=5009) enrolled in a geographically based
      cohort study completed a Health and Lifestyle Questionnaire between October 2000
      and June 2002 that ascertained their colorectal cancer detection practices, as
      well as demographic and other health and lifestyle characteristics. RESULTS:
      Patterns of FOB testing, and sigmoidoscopy or colonoscopy, were similar for men
      and women. The majority of subjects (83.3%) reported no first-degree family
      history of colorectal cancer or bowel conditions, and they were considered to be
      at average risk. Few average-risk subjects reported having a screening FOB test
      within the past two years (7.7% [95% CI 6.7% to 8.7%] of subjects aged 50 to 59
      years and 12.5% [95% CI 10.9% to 14.3%] of subjects aged 60 to 69 years). In men,
      the strongest predictors of having a screening FOB test in the past two years
      were a recent history of prostate-specific antigen testing and educational
      attainment. Among women, the strongest predictors were a recent history of having
      had a Pap test, a recent mammogram, employment status and educational attainment.
      CONCLUSIONS: Screening for colorectal cancer in average-risk adults was
      infrequent in this sample and lagged behind screening for other cancers.
      Screening of average-risk adults occurred primarily in people already accessing
      the health care system, suggesting that public education programs will be
      required to increase screening rates.

PMID- 15997268
TI  - Validation of a short questionnaire in English and French for use in patients
      with persistent upper gastrointestinal symptoms despite proton pump inhibitor
      therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test.
AB  - BACKGROUND: The management of persistent symptoms during acid suppression therapy
      in patients with gastroesophageal reflux disease or dyspepsia might be improved
      if patient-physician communication regarding the presence and character of these
      persistent symptoms were facilitated. AIM: To validate a short, simple
      questionnaire (the Proton pump inhibitor [PPI] Acid Suppression Symptom [PASS]
      test), in English and French, to identify patients with persistent acid-related
      symptoms during PPI therapy and document their response to a change in therapy.
      METHODS: Patients with persistent acid-related symptoms on PPI therapy were
      interviewed to produce a draft, five-item questionnaire; content validity was
      evaluated by focus groups comprising English- and French-speaking patients.
      Psychometric validity was subsequently evaluated in a multicentre, family
      practice-based study of English- and French-speaking patients with persistent
      acid-related upper gastrointestinal symptoms despite PPI therapy. The PASS test,
      Global Overall Symptom scale, Gastrointestinal Symptom Rating Scale (GSRS),
      Quality of Life in Reflux and Dyspepsia questionnaire and Reflux Disease
      Questionnaire were completed at baseline and repeated after one week while
      patients continued their original PPI therapy. All patients then received
      esomeprazole 40 mg once daily for four weeks, after which all questionnaires and
      an evaluation of overall treatment effect were completed. RESULTS: Content
      validity was established in 20 English- and 16 French-speaking patients.
      Psychometric validation in 158 English- and 113 French-speaking patients revealed
      good-to-excellent test-retest reliability coefficients: 0.76 for English; 0.68
      for French. For construct validity, the PASS test showed moderate-to-high
      correlation with the GSRS scale (0.51 for English; 0.43 for French). After four
      weeks of therapy, the PASS test score fell to zero in 30% of English- and 33% of
      French-speaking patients, while the Global Overall Symptom score fell to one (no
      symptoms) in 32% of patients (English- and French-speaking); the PASS test
      demonstrated good responsiveness in comparison with the GSRS, Reflux Disease
      Questionnaire and Quality of Life in Reflux and Dyspepsia questionnaire.
      CONCLUSION: The five-item PASS test is a valid tool for the evaluation of
      persistent acid-related symptoms in patients receiving PPI therapy. It
      demonstrates good content validity, test-retest reliability, responsiveness and
      construct validity in both English and French forms. The PASS test is a simple,
      clinically applicable tool for the identification of patients with persistent
      acid-related symptoms during therapy and the assessment of their responses to a
      change in therapy.

PMID- 15997269
TI  - Pegylated-interferon alpha 2b and ribavirin for recurrent hepatitis C after liver
      transplantation: From a Canadian experience to recommendations for therapy.
AB  - BACKGROUND: Recurrent hepatitis C (HCV) after liver transplantation (LT) is often
      more aggressive and treatments tend to be less successful. Pegylated-interferon
      and ribavirin are the standard of care for the treatment of HCV; however, there
      is limited published experience of its use after LT. OBJECTIVE: To report the
      results of pegylated-interferon alpha 2b (PEG-IFN) plus ribavirin for the
      treatment of recurrent HCV after LT and compare the results with published data.
      METHODS: Thirteen patients with recurrent HCV were treated with PEG-IFN plus
      ribavirin. Liver biopsies demonstrated early-stage disease in eight patients and
      advanced fibrosis in five patients. The average starting dose of PEG-IFN was 0.91
      microg/kg (range 0.5 microg/kg to 1.1 microg/kg) per week and ribavirin was
      started at 662 mg (range 0 mg to 1200 mg) per day. PEG-IFN treatment began an
      average of 24 months after LT (range six to 73 months). The dose of PEG-IFN was
      increased in four patients but only two reached 1.5 microg/kg. The ribavirin dose
      was increased in four, reduced in six and only seven patients reached a ribavirin
      dose greater than 10.6 mg/kg. RESULTS: A sustained virological response was seen
      in four of 13 (30.7%) patients and in four of eight (50%) patients with early
      stage disease compared with zero of five patients with advanced fibrosis (P=0.1).
      Cytopenias were common and therapy was poorly tolerated in four of five patients
      with advanced fibrosis, including acute cellular rejection in three, renal
      failure in two, liver decompensation in four and death in three. CONCLUSIONS:
      Although a reasonable sustained virological response can be achieved with the use
      of PEG-IFN and ribavirin, the treatment is very poorly tolerated by patients with
      advanced-stage recurrent HCV. Treatment should be instituted before the
      development of significant fibrosis after LT.

PMID- 15997270
TI  - Herpes simplex virus type II infection of ileum mesothelium: a case report and
      review of the literature.
AB  - Disseminated herpes simplex virus (HSV) infection usually manifests in the
      immunocompromised. However, anecdotal examples of visceral HSV disease and
      viremia have complicated type I diabetes. A case of a 53-year-old type I diabetic
      patient with bowel obstruction one week subsequent to bronchitis is reported. At
      laparotomy, a perforated segment of ileum was associated with an adhesive
      peritoneal band. HSV cytopathic atypia and HSV immunohistochemical staining were
      confined to fibrocytes and mesothelial cells without involvement of the
      epithelium. Dissemination of symptomatic HSV pneumonia was verified by histology,
      immunohistochemistry, in situ hybridization, polymerase chain reaction and direct
      fluorescence antibody. Intravenous acyclovir resolved symptoms. This is a novel
      documentation of HSV complicating ileal adhesive band disease. Furthermore, this
      case indicates that the HSV cytopathic effect is not unique to the epithelium.
      Disseminated infection can manifest in myofibrocytes and mesothelium,
      distinguishing it from standard epithelial atypia of localized HSV infection.

PMID- 15997271
TI  - Metal nanoparticle-conjugated polymer nanocomposites.
AB  - Recent literature describing nanocomposites of metal nanoparticles and conjugated
      polymers and oligomers are reviewed. Preparation of these nanocomposites by
      chemical and electrochemical methods are described, and the electronic and
      optical properties of these materials are discussed. Some initial applications
      that have been investigated for such nanocomposites are covered.

PMID- 15997272
TI  - Selective oxidation of CO in the presence of H2, H2O and CO2 via gold for use in
      fuel cells.
AB  - An Au/Fe2O3 catalyst prepared using a two-stage calcination procedure achieves
      target conversion and selectivity for the competitive oxidation of dilute CO in
      the presence of moist excess H2 and CO2.

PMID- 15997273
TI  - Dehydrogenation of aliphatic polyolefins catalyzed by pincer-ligated iridium
      complexes.
AB  - We report the first example of the catalytic dehydrogenation of aliphatic
      polyolefins to give partially unsaturated hydrocarbon polymers.

PMID- 15997274
TI  - Dynamic nanoscale Borromean links.
AB  - Employing halogen atom labels on one of the ligand precursors, the lability of at
      least some of the 30 dative and 12 imine bonds stabilizing and constituting the
      three rings of a metallo-Borromean linked compound are scrambled in acidic
      methanolic solution.

PMID- 15997275
TI  - Nanoscale Borromean links for real.
AB  - Borohydride reduction of a Borromean Ring (BR) complex containing six zinc(II)
      ions and 12 imine bonds has resulted in its demetallation, producing a neutral BR
      compound and also its free macrocycle, following cleavage of at least one of the
      imine bonds in the ethanolic reaction mixture.

PMID- 15997276
TI  - Dibenzothiophene-S,S-dioxide-fluorene co-oligomers. Stable, highly-efficient blue
      emitters with improved electron affinity.
AB  - Incorporation of dibenzothiophene-S,S-dioxide units into conjugated fluorene
      oligomers changes the frontier orbital energy levels and presents an effective
      way to increase the electron affinity of these materials, which are highly
      fluorescent with bright blue emission in both solution and the solid state.

PMID- 15997277
TI  - Intramolecular addition of cysteine thiyl radicals to phenylalanine in peptides:
      formation of cyclohexadienyl type radicals.
AB  - The intra-molecular addition of peptide cysteine thiyl radicals to phenylalanine
      yields alkylthio-substituted cyclohexadienyl radicals for the peptides Phe-Cys
      and Phe-Gly-Cys-Gly, i.e. even when Phe and Cys are separated by a Gly residue,
      and presents a possible free radical pathway to thioether-containing peptide and
      protein cross-links.

PMID- 15997278
TI  - Synthesis of a four-coordinate titanium(IV) oxoanion via deprotonation and
      decarbonylation of complexed formate.
AB  - Deprotonation of the titanium formate complex [Ar(t-Bu)N]3TiOC(O)H with LiN(i
      Pr)2 resulted in the release of free CO and the formation of a titanium(IV)
      oxoanion complex, isolated as its lithium salt.

PMID- 15997279
TI  - Square planar bis(imino)pyridine iron halide and alkyl complexes.
AB  - Square planar iron methyl complexes containing bis(imino)pyridine (PDI) ligands
      have been prepared by reductive alkylation of the corresponding ferrous
      dichloride; dialkylation is observed upon treatment with a larger alkyl lithium.

PMID- 15997280
TI  - Monometallic and heterobimetallic azanickellacycles as ethylene polymerization
      catalysts.
AB  - The azanickellacyclic complex (1) produced by trimerization of an isocyanide on
      the nickel atom is found to be a new ethylene polymerization catalyst; catalytic
      activity is increased by incorporation of the second metal to a diimino moiety of
      1 leading to formation of heterobimetallic complexes.

PMID- 15997281
TI  - Extremal acidity of Rees polycyanated hydrocarbons in the gas phase and DMSO--a
      density functional study.
AB  - It is shown by using the density functional theory (DFT) calculations that Rees
      tricyclic[10]annulene 1 and its benzo-annelated derivative 2, substituted by CN
      groups at all peripheral sp2 carbon positions, represent hyperstrong neutral
      superacids in the gas-phase and DMSO.

PMID- 15997282
TI  - Unprecedented reduction of the uranyl ion [UO2]2+ into a polyoxo uranium(IV)
      cluster: synthesis and crystal structure of the first f-element oxide with a
      M6(micro3-O)8 core.
AB  - The smooth comproportionation reaction of the U(VI) and U(III) complexes
      UO2(OTf)2 and U(OTf)3, afforded the hexanuclear U(IV) oxide cluster [U6(micro3
      O)8(micro2-OTf)8(py)8], a rare example of a metal oxide with a M6(micro3-O)8
      core.

PMID- 15997283
TI  - Practical synthesis and guest-guest communication in multi-hemicarceplexes.
AB  - Single molecule hosts carrying three separately encapsulated guests are prepared
      in a seven step sequence in high overall yields.

PMID- 15997284
TI  - Total synthesis and structure validation of (+)-bistramide C.
AB  - The convergent total synthesis of the marine natural product (+)-bistramide C
      confirms the a priori assignments of its relative and absolute configurations,
      which were originally based on the combined application of [alpha]D analysis,
      NMR, and synthesis.

PMID- 15997285
TI  - Stereoselective E/Z photoisomerization of oxazolidinone functionalized
      enecarbamates: direct and triplet sensitized irradiation.
AB  - Oxazolidinone-functionalized enecarbamates undergo diastereoselective E/Z
      photoisomerization upon direct and triplet sensitized irradiations with
      chiral/achiral sensitizers, showing that the enhanced product
      diastereoselectivity depends on the solvent and temperature.

PMID- 15997286
TI  - An excimer emission approach for patterned fluorescent imaging.
AB  - Selective removal of t-Boc protecting groups in a polymer film imbedded, pyrene
      containing calixarene derivative results in the generation of a patterned
      fluorescence image without employing wet developing processes.

PMID- 15997287
TI  - (6-4)-photolyase activity requires a charge shift reaction.
AB  - A model compound containing a thymine oxetane moiety linked to a flavin
      chromophore was investigated regarding (6-4)-photolyase activity. The need for a
      charge shift reaction was demonstrated by a detailed pH-dependent kinetic
      analysis.

PMID- 15997288
TI  - Surfactant-promoted novel reductive synthesis of supported metallic Cu
      nanoclusters and their catalytic performances for selective dehydrogenation of
      methanol.
AB  - We have found a surfactant-promoted novel reductive synthesis of metallic Cu
      nanoclusters on metal oxides under hydrothermal synthesis conditions, which are
      active for the selective dehydrogenation of methanol.

PMID- 15997289
TI  - Visible light decomposition of ammonia to dinitrogen by a new visible light
      photocatalytic system composed of sensitizer (Ru(bpy)(3)2+), electron mediator
      (methylviologen) and electron acceptor (dioxygen).
AB  - Visible light decomposition of aqueous ammonia to dinitrogen was successfully
      achieved by using a new photocatalytic system based on a molecular photoelectron
      relay composed of a sensitizer (Ru(bpy)(3)2+), an electron mediator
      (methylviologen) and an electron acceptor (dioxygen), which can be used as a
      visible light-driven photocatalyst instead of UV-driven semiconductors.

PMID- 15997290
TI  - Stereoselective gamma-lactam synthesis via palladium-catalysed intramolecular
      allylation.
AB  - A novel route to the synthesis of 3-(tolylsulfonyl)-4,5-cis-disubstituted gamma
      lactams using a diastereoselective palladium-catalysed intramolecular allylation
      of amino acid-derived allylic carbonates has been developed.

PMID- 15997291
TI  - Solvent-free methylthiomethyllithium [LiCH2SMe]infinity: solid state structure
      and thermal decomposition.
AB  - Solvent-free [LiCH2SMe]infinity forms a layer structure consisting of four-
      (Li2C2), five- (Li2CS2), and six-membered (Li2C2S2) rings in the solid state; the
      compound violently explodes upon heating to T=160+/-5 degrees C under an argon
      atmosphere.

PMID- 15997292
TI  - Concise syntheses of bacteriohopanetetrol and its glucosamine derivative.
AB  - This study describes the syntheses of bacteriohopanetetrol and its glucosamine
      derivative through a key direct coupling of a ribose derivative to the hopane
      skeleton.

PMID- 15997293
TI  - Highly regioselective and diastereoselective epoxidation of allylic amines with
      Oxone.
AB  - Allylic amines (as their protonated ammonium salts) can be epoxidised with high
      syn diastereoselectivity and regioselectivity at the proximal alkene in
      substrates with several double bonds using Oxone. The protonated ammonium cation
      activates the Oxone by hydrogen bonding, thus promoting the oxidation of groups
      within the vicinity of the complex.

PMID- 15997294
TI  - Enantioselective hydrogenation of alkenes and imines by a gold catalyst.
AB  - A new neutral dimeric gold(I) complex bearing the 1,2-bis[(2R,5R)-2,5
      dimethylphospholanebenzene] [(R,R)-Me-Duphos] ligand has been synthesized which
      catalyzes the asymmetric hydrogenation of alkenes and imines under mild reaction
      conditions.

PMID- 15997295
TI  - Aminosilylation of arynes with aminosilanes: synthesis of 2-silylaniline
      derivatives.
AB  - The nitrogen-silicon sigma-bond of aminosilanes added across the triple bond of
      arynes to give varied 2-silylaniline derivatives straightforwardly.

PMID- 15997296
TI  - Achiral molecules in non-centrosymmetric space groups.
AB  - A database survey of molecules with and without a chiral centre indicates
      molecular flexibility plays a role in space group choice.

PMID- 15997297
TI  - Ruthenium-catalysed asymmetric hydrogenation of ketones using QUINAPHOS as the
      ligand.
AB  - Highly enantioselective ruthenium-catalysed hydrogenation of aromatic ketones is
      achieved with (Ra,S(C))-QUINAPHOS in the presence of achiral and chiral diamines
      as co-catalysts.

PMID- 15997298
TI  - Mono- and digallane complexes of a tridentate amido-diamine ligand.
AB  - Bis(2-dimethylaminoethyl)amido gallane, H2GaN(CH2CH2NMe2)2, that melts at 27
      degrees C and remains stable upon heating at 55 degrees C for two days, was
      synthesized either from the reaction of the quinuclidine adduct of
      monochlorogallane with the lithium salt of the corresponding amine, or from the
      reaction of trimethylamine gallane and the amine; the latter affords an unusual
      co-product with both GaH2 and GaH3 bonded to the same amido nitrogen.

PMID- 15997299
TI  - S(O)-pixyl protecting group as efficient mass-tag.
AB  - We report herein the design, preparation and first applications of novel trityl
      tags with adjustable stability, efficient as protecting groups or MS analytes.

PMID- 15997300
TI  - The Hildebrand solubility parameters, cohesive energy densities and internal
      energies of 1-alkyl-3-methylimidazolium-based room temperature ionic liquids.
AB  - The Hildebrand solubility parameters, cohesive energy densities and internal
      energies of 1-alkyl-3-methylimidazolium-based room temperature ionic liquids were
      determined by the intrinsic viscosity method and their dependencies on the length
      of the alkyl group analyzed.

PMID- 15997301
TI  - A very sensitive high-resolution NMR method for quadrupolar nuclei: SPAM-DQF
      STMAS.
AB  - We show that by combining the intrinsically larger (with respect to MQMAS)
      efficiency of Double-Quantum Filtered Satellite-Transition MAS (DQF-STMAS), with
      the large S/N gain of the Soft-Pulse Added Mixing (SPAM) concept, a new very
      sensitive high-resolution solid-state NMR method can be obtained for semi-integer
      quadrupolar nuclei.

PMID- 15997302
TI  - Putrescine homologues control silica morphogenesis by electrostatic interactions
      and the hydrophobic effect.
AB  - A systematic model study on the role(s) of putrescine homologues on
      silicification is presented and it is proposed that electrostatic forces between
      additive and silicic acid, and the hydrophobic behaviour of the additives are
      both important in silicification.

PMID- 15997303
TI  - New diphosphine ligands based on diphenyl ether for the Pd-catalyzed CO/ethene
      copolymerization.
AB  - The catalytic activity and selectivity of palladium(II) complexes of new,
      flexible bidentate ligands in the CO/ethene copolymerization reaction have been
      found to change considerably with the steric properties of the ligands.

PMID- 15997304
TI  - Enzyme nanoparticles-based electronic biosensor.
AB  - A simple and effective method to prepare an enzyme electronic biosensor by
      immobilizing enzyme nanoparticles directly onto the gold electrode surface is
      described; prepared horseradish peroxidase nanoparticles have been successfully
      used to develop reagentless electronic biosensors for H2O2 detection without
      promoters and mediators and offer great potential to develop enzyme-based
      electronic biosensors.

PMID- 15997305
TI  - Resolution of N-linked oligosaccharides in glycoproteins based upon
      transglycosylation reaction by CE-TOF-MS.
AB  - The resolution of asparagine-type oligosaccharides in glycoproteins was carried
      out by combination of the transglycosylation reaction and CE-TOF-MS. The
      oligosaccharides enzymatically transferred to a fluorescent acceptor (NDA-Asn
      GlcNAc) with Endo-M. The resulting fluorescent-oligosaccharides were separated by
      CE and detected by TOF-MS. Disialo-Asn was successfully identified by the
      proposed procedure. Application to oligosaccharides in ovalbumin was also
      described in this communication.

PMID- 15997306
TI  - [Maternal posture and its influence on birthweight].
AB  - OBJECTIVE: To analyze the relationship between maternal posture/physical activity
      and inadequate birthweight. METHODS: Prospective cohort study involving 152
      pregnant women from a public low-risk antenatal care facility. Three interviews
      evaluating the frequency of physical activity were administered to each pregnant
      woman during gestation. Birthweight (inadequate when <3,000 g and adequate when >
      or =3,000 g) was the dependent variable and the frequency of physical activity
      the independent variable. Statistical analysis was performed using logistic
      univariate analysis and multiple regression controlling for schooling, smoking,
      living with spouse, and baseline nutritional status. RESULTS: The practice of
      walking for at least 50 minutes during the first period of pregnancy was
      identified as a protective factor against inadequate birthweight (adjusted
      OR=0.44; 95% CI: 0.20-0.98). Standing for 2.5 hours or longer during the second
      semester of pregnancy was associated with increased risk (adjusted OR=3.23; 95%
      CI: 1.30-7.99). Dose-response relationships were identified for washing clothing
      by hand and cooking (p-value for linear trend <0.01 and 0.05, respectively).
      After confounder control, only washing clothing during the second trimester of
      gestation remained statistically significant. CONCLUSIONS: Our results show the
      importance of medical orientation regarding posture and physical activity during
      antenatal care, aiming at the reduction of inadequate birthweight.

PMID- 15997307
TI  - Climacteric symptoms and quality of life: validity of women's health
      questionnaire.
AB  - OBJECTIVE: To evaluate the reliability and validity of the Portuguese version of
      the Women's Health Questionnaire. METHODS: In order to evaluate the Women's
      Health Questionnaire (WHQ), an analytical cross-sectional study was carried out
      at the women's menopause outpatient clinic of a university hospital in Sao Paulo,
      Brazil. There were studied 87 women in perimenopause or menopause, defined as
      experiencing at least one year's absence of menstrual flow. The following
      variables were collected: demographic data, clinical variables (Kupperman index
      and correlate numeric scale) and quality of life indexes (SF-36 and utility).
      RESULTS: The WHQ proved to be a questionnaire easily translated into Portuguese
      and well-adjusted to Brazilian women. The internal consistency of the overall WHQ
      was excellent (Cronbach alpha =0.83; 95% CI: 0.71-0.91). Test-retest reliability
      was also excellent (intraclass correlation coefficient [ICC]=0.92; 95% IC: 0.86
      0.96) and had good absolute agreement (0.84; 95% CI: 0.71-0.92). A satisfactory
      clinical validity was observed. The construct validity was corroborated by clear
      associations with others scales. A good index of responsiveness after the
      intervention was reached. CONCLUSIONS: The Portuguese version of the WHQ is of
      easy and fast administration and understanding. Its measuring properties were
      related, allowing its use in the evaluation of Brazilian climacteric women's
      quality of life for various purposes.

PMID- 15997308
TI  - [Breast cancer's secondary prevention and associated factors].
AB  - OBJECTIVE: To evaluate the prevalence of secondary prevention of breast cancer
      and associated factors. METHODS: A population-based cross-sectional study was
      conducted in the city of Pelotas, southeastern Brazil, in 2002. The study sample
      comprised 879 women aged 40 to 69 years. Information was collected on
      demographic, social, economic, behavioral, biological and care management
      variables. Statistical analysis based on Poisson regression model was carried
      out. RESULTS: The prevalence of breast self-examination (BSE) was 83.5% (95% CI:
      80.9-85.9). Of them, 80.4% (95% CI: 77.3-83.2) carried out BSE at least once a
      month. The prevalence of clinical breast examination was 83.3% (95% CI: 80.6
      85.7). Mammography was occasionally performed in 70% (95% CI: 66.8-73.0) of the
      sample. Of these women, 83.7% (95% CI: 80.5-86.6) underwent mammography at least
      once in the last two years. Sixty-two percent (95% CI: 58.7-65.2) of the women
      interviewed attended a gynecological visit at least once in the last year. The
      factors mainly associated to the high prevalence of secondary prevention of
      breast cancer were: higher social status; greater association of risk factors for
      breast cancer; family history of breast cancer; hormone replacement therapy and
      previous breast biopsy or surgery. CONCLUSIONS: Preventive measures for breast
      cancer have been widely taken in the study sample; however, data points out to
      some limitations related to efficacy. Social and economic status seems to be a
      major determinant to gynecological care access and, consequently, access to
      secondary prevention of breast cancer.

PMID- 15997309
TI  - [Obstetric delivery and risk of neonatal mortality in Goiania in 2000, Brazil].
AB  - OBJECTIVE: To determine factors associated to vaginal delivery and increased
      neonatal mortality in cohort studies of newborns. METHODS: A retrospective cohort
      study was carried out using linkage data from the Information System on Live
      Births and Mortality Data System database, which included all newborns in Goiania
      for the year 2000. A stratified analysis of delivery routes and maternity
      hospitals by risk factors of neonatal mortality was conducted through the
      calculation of relative risk at a 5% significance level. Statistical analyses
      were carried out using the Chi-square test at a 5% significance level. RESULTS:
      Vaginal deliveries were more commonly seen than cesarean sections in situations
      where there was an increased risk of neonatal mortality. Public hospitals, where
      vaginal deliveries predominated, were sought by the majority of those pregnant
      women with an increased risk of neonatal mortality. Private hospitals, not
      affiliated to the public-funded Brazilian Healthcare System (SUS) and where the
      incidence of cesarean section was as high as 84.9%, opted for vaginal delivery in
      situations of greater risk, such as extreme prematurity and very-low-birth-weight
      infants. CONCLUSIONS: The association between vaginal delivery and increase
      neonatal mortality resulted from a selection bias due to the distribution of
      pregnant women in the hospital network. In addition, this selection bias also
      resulted from an almost universal preference for cesarean sections in low-risk
      pregnancies as opposed to vaginal delivery for pregnancies with an increased risk
      of neonatal mortality.

PMID- 15997310
TI  - [Drug use during in-hospital birth delivery stay].
AB  - OBJECTIVE: Drug use in birth delivery has not been enough explored in the
      literature. It is a significant issue to be discussed on the theme of rational
      drug use. The objective was to study drug use during birth delivery stay in
      maternity hospitals. METHODS: A cross-sectional study was carried out using
      medical records of two private and public maternity hospitals of Belo Horizonte,
      Brazil. Data were collected on pregnant women's identification, pregnancy,
      delivery and drug prescribed from medical records of public hospitals and medical
      records and billing invoice of private maternity hospitals. Statistical analysis
      was conducted using odds ratio by the Chi-square test and means by t-Student
      test. RESULTS: Mean in-hospital stay was 2.2 days and it was lower in the private
      maternity hospital. Cesarean sections were performed in 52.7% of all births,
      31.3% in the public hospital and 64.5% in the private hospital. Peridural
      anesthesia was used in 72.8% of births and local anesthesia in 22.4% (25.3% and
      63.7% of births in the public and 98.2% and 0.4% in the private hospital). All
      women received drugs (minimum of 3 and maximum of 19 different drugs) during
      their hospital stay. Eighty-three medications (97 active ingredients) were
      utilized at a total frequency of 3,429. The higher average drug use was 8.5 drugs
      per woman, in the private maternity hospital. CONCLUSIONS: There was a
      significant difference in drug use between the two maternity hospitals, being it
      higher in pre- and during birth delivery procedures. The results suggest a
      preeminent drug use compared to those of other few studies available in the
      literature. The disproportionate number of cesarean sections and anesthesia
      explain the differences observed.

PMID- 15997311
TI  - [Accidental home deliveries in southern Sao Paulo, Brazil].
AB  - OBJECTIVE: To identify the frequency, risks of fetal and early neonatal mortality
      and the determinants of accidental home deliveries. METHODS: A population-based
      case control study of fetal and early neonatal deaths was carried out in the
      southern area of Sao Paulo, Brazil. Data were collected through home interviews
      and hospital record reviews. The reasons reported by the mothers were obtained
      from interviews and risk factors for home delivery were obtained comparing home
      to hospital deliveries. Data were analyzed separately for fetal and early
      neonatal deaths and survivors. Odds ratios, 95% confidence intervals and Fisher's
      exact test were used in estimating risk factors and mortality risk. RESULTS: The
      0.2% frequency of home deliveries was underestimated in the live births
      information system. After adjustment, it reached 0.4%, comparable to other urban
      areas in Europe. All home deliveries identified were accidental and were
      associated to an increased fetal and early neonatal mortality. Mothers' social
      conditions and pregnancy characteristics were associated to accidental home
      deliveries and these factors are different outcomes studied (fetal losses, early
      neonatal deaths and survivors). In 30%, mothers reported lack of available
      transportation to the hospital as a reason for home delivery. Failure of health
      services in identifying labor women and non-availability of emergency care
      contributed to accidental home deliveries. CONCLUSIONS: Though rare events in
      urban areas, accidental home deliveries should be of special concern to health
      services because they seem to be avoidable and imply in increased risk of death.

PMID- 15997312
TI  - [The services for women victims of sexual violence: a qualitative study].
AB  - OBJECTIVE: To assess public services attending female victims of sexual violence
      in the city of Sao Paulo. METHODS: This is a qualitative study conducted in two
      public services attending female victims of sexual violence. Interviews with 42
      women were conducted, 13 of whom had sought these services for assistance and 29
      were professionals working in these services. Evaluation of the services was
      based on the categories: reception, access, resolvability and sanitary
      responsibility. RESULTS: The analysis of the interviews per category has shown
      that there was reception in both services, problems with respect to access due to
      the lack of information concerning these services, and quality resolvability with
      a multi-professional team. As to the sanitary responsibility, it is present in
      these specialized services but is deficient in the emergency services and basic
      health care units. Many women are unaware of the rights they are entitled to with
      respect to specialized services. Frequently their late arrival compromises the
      efficacy of care. There are deficiencies both in terms of reference and counter
      reference. CONCLUSIONS: The results ratify the importance of these services and
      the need for their decentralized expansion. Health courses should introduce the
      theme of sexual violence at the undergraduate level.

PMID- 15997313
TI  - [Disability among elderly women in Brazil].
AB  - OBJECTIVE: To estimate disability rates and explore associations, identifying the
      most significant socioeconomic markers associated with the prevalence of mobility
      disability among elderly women. METHODS: National mobility disability rates were
      estimated based on information from the 1998 National Household Survey (PNAD),
      conducted by the Instituto Brasileiro de Geografia e Estatistica. The present
      study analyzes the elderly women population, totaling 16,186 subjects. Logistic
      regression models were constructed considering 'difficulty walking 100 meters' as
      the dependent variable. RESULTS: The prevalence of markers of mild, moderate and
      severe disability was greater among women, and increased with age. In logistic
      regression analysis, markers most strongly associated with increased prevalence
      of mobility disability were age, gender, low schooling, and low income. Rural
      residence was also associated with reduced prevalence. CONCLUSIONS: Our results
      suggest potential risk factors for the development of functional decline in
      elderly women, given that the associations encountered were consistent with those
      reported by other studies in the literature.

PMID- 15997314
TI  - [Home care in the Brazilian National Health System (SUS)].
AB  - OBJECTIVES: To assess home care programs implemented in three cities and to
      identify components indicating the integration of these programs into the reform
      of health care. METHODS: An exploratory descriptive study with a qualitative
      approach was carried out in the cities of Marilia and Santos, state of Sao Paulo,
      and Londrina, state of Parana, Brazil. Empirical data was obtained from
      interviews with five nurses and one social worker who worked in home care
      services, and through analysis of reports on these programs. The data was
      analyzed using the discourse analysis technique. RESULTS: The findings show the
      importance of home care services as a strategy for dehospitalization and
      humanization of care. Components were identified showing that home care focused
      on building up a health care model based on light technology, and
      multiprofessional and intersectorial work. It was found that, despite advances in
      the implementation of home care services, there are obstacles for an effective
      health care model change, such as ineffective referral and counter-referral
      mechanisms and complex relationship of health care providers with service users,
      their families and caregivers. CONCLUSIONS: Care provided by home care programs
      is a strategy to decentralized care based on hospitals and to build up a new
      approach focused on health promotion and prevention, reducing risks and
      humanizing care. Strategies must be drawn up to allow its implementation in the
      public health network.

PMID- 15997315
TI  - [Monitoring of airborne fungus and yeast species in a hospital unit].
AB  - OBJECTIVE: To monitor and characterize airborne filamentous fungi and yeasts from
      abiotic and biotic sources within a hospital unit. METHODS: Collections were
      carried out on a monthly basis, at two different time periods, from the adult and
      pediatric intensive care units and surgical center of a hospital in Araraquara,
      Southeastern Brazil. Collection of airborne fungi was carried out using a simple
      stage Andersen sample. The presence of yeasts was investigated in samples taken
      from the hands and oropharynx of staff members as well as from the surface of
      beds and doorknobs inside the critical areas. RESULTS: Thirty-two genera of
      airborne fungi and were recovered from the surgical center and 31 from the
      intensive care units. Genera most frequently isolated were Cladophialophora spp.,
      Fusarium spp., Penicillium spp., Chrysosporium spp. e Aspergillus spp. During the
      study period, a new unit was built in the hospital, which coincided with an
      increase in Cladophialophora spp., Aspergillus spp., and Fusarium spp. colony
      counts. Yeasts were found in 39.4% of samples obtained from healthcare staff
      (16.7% from interdigital spaces, 12.1% from nailbeds, and 10.6% from oropharynx)
      and in 44% of furniture samples, with a predominance of the Candida genus ((C.
      albicans, C. guilliermondii, C. parapsilosis e C. lusitaniae), followed by
      Trichosporon spp. CONCLUSIONS: We found a relatively high number of airborne
      fungi (potentially pathological) in special areas and expressive levels of yeasts
      in both biotic and abiotic samples. Microbiological and environmental monitoring
      should be conducted, especially in special areas which include immunocompromised
      patients, who are more susceptible to the exposure to environmental and staff
      derived pathogens.

PMID- 15997316
TI  - Factors associated with infant feeding practices after hospital discharge.
AB  - OBJECTIVE: To assess factors associated with infant feeding practices on the
      first day at home after hospital discharge. METHODS: A total of 209 women, who
      had a child aged four months or less and were living in Itapira, Brazil, were
      interviewed during the National Immunization Campaign Day in 1999. Statistical
      analysis was performed using the Chi-square test and a logistic regression model
      was used for verifying an association between dependent and independent
      variables. RESULTS: Women aged 25.5 years on average and 18.2% were teenagers.
      Fifty-three percent of the women delivered vaginally and most vaginal deliveries
      (78.5%) took place in the public hospital. The prevalence of exclusive
      breastfeeding on the first day at home was 78.1% and 11.6% of the infants were
      receiving formula at this time. The only factor associated with EBF on the first
      day at home was being a teenaged-primiparous mother (OR=9.40; 95% CI: 1.24
      71.27). This association remained statistically significant even after
      controlling for type of delivery and hospital where the birth took place. Feeding
      formula on the first day at home was only significantly associated with the
      hospital (i.e., birth at the city hospital was a protective factor (OR=0.33; 95%
      CI: 0.13-0.86), even after controlling for vaginal delivery. CONCLUSIONS: On the
      first day at home after hospital discharge, teenaged-primiparous mothers were
      more likely to exclusive breastfeeding as well as those infants born in the
      municipal public hospital. Further studies are needed from a multidisciplinary
      approach.

PMID- 15997317
TI  - Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled
      trial.
AB  - OBJECTIVE: To compare the reactogenicity of three yellow fever (YF) vaccines from
      WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo. METHODS:
      The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro,
      Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil)
      were administered ("day 0") following standardized procedures adapted to allow
      blinding and blocked randomization of participants to coded vaccine types.
      Adverse events after immunization were ascertained in an interview and in diary
      forms filled in by each participant. Liver enzymes were measured on days 0, 4-20
      and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up.
      The immune response was verified through serologic tests. RESULTS: Participants
      were mostly young males. The seroconversion rate was above 98% among those
      seronegative before immunization. Compared to placebo, the excess risk of any
      local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse
      events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of
      events leading to search for medical care or to interruption of work activities
      ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days
      after vaccination. Variations in liver enzyme levels after vaccination were
      similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse
      events post-immunization against YF, accounting for the background occurrence of
      nonspecific signs and symptoms, was shown for the first time to be similar for
      vaccines from 17D and 17DD substrains. The data also provided evidence against
      viscerotropism of vaccine virus.

PMID- 15997318
TI  - Determinants of vaccination after the Colombian health system reform.
AB  - OBJECTIVE: To assess the effects of individual, household and healthcare system
      factors on poor children's use of vaccination after the reform of the Colombian
      health system. METHODS: A household survey was carried out in a random sample of
      insured poor population in Bogota, in 1999. The conceptual and analytical
      framework was based on the Andersen's Behavioral Model of Health Services
      Utilization. It considers two units of analysis for studying vaccination use and
      its determinants: the insured poor population, including the children and their
      families characteristics; and the health care system. Statistical analysis were
      carried out by chi-square test with 95% confidence intervals, multivariate
      regression models and Cronbach's alpha coefficient. RESULTS: The logistic
      regression analysis showed that vaccination use was related not only to
      population characteristics such as family size (OR=4.3), living area (OR=1.7),
      child's age (OR=0.7) and head-of-household's years of schooling (OR=0.5), but
      also strongly related to health care system features, such as having a regular
      health provider (OR=6.0) and information on providers' schedules and requirements
      for obtaining care services (OR=2.1). CONCLUSIONS: The low vaccination use and
      the relevant relationships to health care delivery systems characteristics show
      that there are barriers in the healthcare system, which should be assessed and
      eliminated. Non-availability of regular healthcare and deficient information to
      the population are factors that can limit service utilization.

PMID- 15997319
TI  - [Reliability of reported data from adolescent and their mothers in a health
      survey].
AB  - OBJECTIVE: To estimate the reliability of data obtained from questionnaires
      applied to adolescents and their mothers in a health survey. METHODS: Data from
      population-based survey conducted with a one-stage random cluster area sampling
      of residents in the urban area of Salvador, Brazil, were assessed. The study
      sample comprised 82 pairs of adolescent workers aged 10 to 14 years and their
      mothers. After interviewing the adolescents, in a second visit, their mothers
      were invited to answer a similar questionnaire applied by a blinded interviewer.
      Respiratory and depressive symptoms, sleep pattern changes and distress in the
      neighborhood and at school were the variables analyzed. Reliability was measured
      using proportion of agreements and kappa index of agreement statistics. RESULTS:
      Overall agreement and kappa index were low. Mothers have provided more positive
      answers than adolescents, resulting in a negative bias. Reliability was higher
      among boys for all answers when compared to girls, except for sleep patterns
      changes. For depressive symptoms, mother's education level was negatively
      associated with agreement for both genders. CONCLUSIONS: Information from
      adolescents differs from that obtained from mothers. It is worth noticing that
      poor agreement does not impair validity, which needs to be examined in further
      studies.

PMID- 15997320
TI  - Pediculus capitis infestation according to sex and social factors in Argentina.
AB  - OBJECTIVE: To determine the intensity of Pediculus capitis infestation
      (abundance) among Argentinean schoolchildren. Children's sex and social stratum
      were analyzed as modifiers of the general prevalence and degree of parasitism.
      METHODS: The study included 1,370 schoolchildren (692 girls, 678 boys) from 26
      schools of the province of La Rioja (21 public schools, five private schools).
      Classic prevalence was obtained as the percentage of children with nits and/or
      lice. Moreover, five degrees of parasitism were classified: 0) children with no
      signs of pediculosis; 0+) children with evidence of past infestation; 1) children
      with a recent infestation and low probability of active parasitism; 2) children
      with a recent infestation and high probability of active parasitism; 3) children
      with mobile lice (active pediculosis). RESULTS: The general prevalence was 61.4%
      (girls: 79%; boys: 44%, p<0.001). Private schools showed lower prevalence than
      public schools (p=0.02), especially due to the low prevalence in boys. Fifty
      percent of children were classified in classes 0 and 0+, 22% in class 1; and 28%
      in grades 2 and 3. The proportion of children in grade 3 was higher in public
      schools than in private schools. There were significant sexual differences in the
      intensity of parasitism for grades 2 and 3, where girls' rates exceeded twice
      those of boys'. CONCLUSIONS: Sex and social stratum are important modifiers of P.
      capitis general prevalence and degree of infestation. The classification of
      children by intensity of infestation allowed a more precise delimitation of this
      condition, which is especially important for disease surveillance and application
      of control measures.

PMID- 15997321
TI  - [Spatial analysis of dengue transmission in a medium-sized city in Brazil].
AB  - OBJECTIVE: To perform spatial analysis on dengue transmission in a medium-sized
      city in the interior of the State of Sao Paulo, Brazil, covering the period from
      September 1990 to August 2002. METHODS: Autochthonous cases with confirmation by
      laboratory tests were utilized. Population data on the city of Sao Jose do Rio
      Preto were obtained from the Brazilian Institute for Geography and Statistics and
      the municipal authorities. The cases were georeferenced according to street
      addresses and clustered according to the 432 census tracts in the municipality,
      thus resulting in thematic maps. RESULTS: A rising trend in annual incidence was
      noted, with a peak in 2000/2001. From 1990 to 1994 the length of the transmission
      period reached a maximum of five months per year. This period increased in length
      over subsequent years. In the final year investigated, transmission occurred in
      all twelve months, without interruptions. Analysis of the period of highest
      incidence showed that the transmission did not occur uniformly. While 29% of the
      tracts registered incidences of less than 1,000 cases per 100,000 inhabitants, 5%
      of them had more than 5,000 cases. CONCLUSIONS: A process of increasing
      endemicity was observed, with transmission throughout the year, without the need
      for virus introducers. The endemic characteristic of the transmission and the
      differentiated occurrence according to areas need to be taken into account when
      developing strategies for dengue control.

PMID- 15997322
TI  - [Economic analysis of a screening program for diabetes mellitus in Brazil].
AB  - OBJECTIVE: Diabetes mellitus is a common disease and costly public health concern
      and an expressive number of affected individuals have undiagnosed diabetes
      mellitus. In 2001, the Brazilian Ministry of Health conducted a national diabetes
      screening campaign. The purpose of this study was to estimate the yield and
      economic impact of this screening strategy. METHODS: Based on positive screenees
      (fasting glucose >100 mg/dL or nonfasting >140 mg/dL) probable new cases of
      diabetes were estimated and a decision analytic model was built up. Primary and
      secondary data were used to estimate screening cost (in Brazilian Reais, R$) and
      yield (new cases of diabetes detected), assuming a single-payer-perspective.
      Sensitivity analyses were performed. RESULTS: Assuming a prevalence of
      undiagnosed diabetes mellitus of 4.8%, probable new cases of diabetes were
      518,579 (23 new cases per 1,000 subjects screened), considering that 33% of
      positive-screening individuals underwent confirmatory glucose testing. The cost
      per new case of diabetes diagnosed would be R$89. The results were sensitive to
      percentage of confirmatory tests performed. CONCLUSIONS: The costs of nationwide
      community screening in Brazil were significant, however, in absolute terms lower
      than those described by other countries.

PMID- 15997323
TI  - [Occupational noise as a risk factor for work-related injuries].
AB  - OBJECTIVE: To assess whether exposure to occupational noise is an important risk
      factor for work-related injuries. METHODS: A population-based case-control study
      was performed. Data collection was carried out from May 16, 2002 to October 15,
      2002 in the city of Botucatu, southeast Brazil. Cases were defined as workers who
      had suffered typical work-related injuries in a 90-day period previously to the
      study, and who identified through systematic random sampling of their households.
      Controls were non-injured workers randomly sampled from the same population,
      matched on 3:1 ratio according to sex, age group and census track. A multiple
      logistic regression model was adjusted, where the independent variable was
      exposure to occupational noise, controlled for covariates of interest. RESULTS: A
      total of 94 cases and 282 controls were analyzed. An adjusted multiple regression
      model showed that "work always exposed to high-level noise" and "work sometimes
      exposed to high-level noise" were associated to a relative risk for work-related
      injuries of about 5.0 (95% CI: 2.8-8.7; p<0.001) and 3.7 (95% CI: 1.8-7.4;
      p=0.0003) respectively, when work not exposed to noise was taken as a reference,
      controlled for several covariates. CONCLUSIONS: Based on the study findings,
      investing in hearing conservation programs, particularly those for controlling
      noise emission at its source, is justifiable aiming at both hearing health
      maintenance and reduction of work-related injuries.

PMID- 15997324
TI  - [Comparative study of the perception of urban noise].
AB  - OBJECTIVE: To comparatively analyze the perception of daily urban noise between
      residents of an acoustically and a non-acoustically controlled area. METHODS: Two
      urban areas were selected through objective assessments of equivalent sound
      levels and defined as a non-acoustically and an acoustically controlled area. A
      random sample of each area was selected and a questionnaire was applied to its
      residents. Statistical indicators of urban noise perception were generated
      through factorial multivariate analysis. RESULTS: The average sound level (Leq)
      found in the downtown district (a non-acoustically controlled area) was 72.9
      dB(A) and in the acoustically controlled area was 53.3 dB(A). Three statistical
      indicators were generated through factorial multivariate analysis: temporary
      perception, perception of atypical noises and sources and disturbances.
      CONCLUSIONS: Residents of the acoustically controlled area reported increased
      noise level. The sound level in the downtown district has remained practically
      constant and much above the standards established by local law. The generated
      indicators are useful parameters to characterize the perception to continuous
      noise exposure in the population.

PMID- 15997325
TI  - [Bioethics, critical solidarity and organic volunteering].
AB  - OBJECTIVE: The study proposes "critical solidarity" as a value to be incorporated
      into the 21st century's bioethics agenda and as an instrument to guide people and
      associations in volunteer praxis. METHODS: To explain how solidarity materializes
      itself, the motivations for engaging in volunteer activities in associations that
      integrate the corps of volunteers of the Instituto Nacional do Cancer [National
      Cancer Institute] in Rio de Janeiro, Brazil, are analyzed. The data for analysis
      were obtained by applying two instruments. The first one consists of a
      questionnaire divided into 2 parts: one part identifies the socioeconomic
      profile, and the other identifies solidarity as a value that motivates volunteer
      activity. The second instrument comprises of semi structured interviews utilized
      to collect supplementary data for analysis. RESULTS: The results indicate that
      volunteering is based on three basic motivations: a) personal motivations related
      to life as a volunteer, b) motivations resulting from professed beliefs, and c)
      motivations aroused by the feeling of solidarity. CONCLUSIONS: It was concluded
      that the incorporation of critical solidarity requires a rupture with the
      detected model of patronizing volunteering; it implies explicating the common
      selfish interests that permeate volunteer activities and qualify an organic
      volunteering, that is, volunteering which is politically aware and committed to
      responding to the specific demands of the present time.

PMID- 15997326
TI  - [Emission of aldehydes from light duty diesel vehicles].
AB  - OBJECTIVE: To characterize acetaldehyde and formaldehyde emissions, which are
      harmful gases to human health and not yet regulated for diesel engines. METHODS:
      Standardized tests were performed in four diesel light duty commercial vehicles,
      using a frame dynamometer and test procedure FTP-75. The pollutants were analyzed
      by high performance liquid chromatography. RESULTS: Results have shown
      acetaldehyde emission ranged from 5.9 to 45.4 mg/km, and formaldehyde emission
      from 16.5 to 115.2 mg/km. The average emission for aldehyde sum was 58.7 mg/km,
      ranging from 22.4 to 160.6 mg/km. The proportion between the two substances
      remained constant, close to 74% for formaldehydes and 26% for acetaldehydes.
      CONCLUSIONS: The emission of diesel vehicle aldehydes was significant when
      compared with actual spark ignition vehicle emissions, or with the foresee limit
      for Otto cycle vehicles in Brazilian legislation. Establishing emission limits
      for these substances also in diesel vehicles is imperative in the light of the
      vehicle fleet growth, toxicity of these compounds, and their contribution as
      precursors in ozone gas formation reactions in low troposphere.

PMID- 15997327
TI  - Sugar content in liquid oral medicines for children.
AB  - The most sold and/or prescribed liquid oral medicines for children in Tubarao,
      Southern Brazil, were assessed. Their sugar concentration was tested and compared
      to those in their directions for use. All pharmacies and pediatricians working in
      the city were visited by a previously trained interviewer. Pre-tested
      questionnaires were applied in order to assess the most sold pediatric as well as
      the most prescribed pediatric liquid oral medicines. Three samples of each
      medicine were analyzed by Lane-Eynon general volumetric method. Among the 14 most
      sold/prescribed medicines only four did not have sugar contents (analgesic,
      cortisone, and syrups). Sugar concentration ranged from 8.59 g/100 g of drug
      (SD=0.29 g/100 g) to 67.0 g/100 g of drug (SD=6.07 g/100 g). Only 50.0% of the
      total medicines that presented sugar in their ingredients showed this information
      in their directions.

PMID- 15997328
TI  - Modern cancer epidemiological research: genetic polymorphisms and environment.
AB  - Individual cancer susceptibility seems to be related to factors such as changes
      in oncogenes and tumor suppressor genes expression, and differences in the action
      of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological
      studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and
      cancer have revealed low relative risks. Research considering genetic
      polymorphisms prevalence jointly with environmental exposures could be relevant
      for a better understanding of cancer etiology and the mechanisms of
      carcinogenesis and also for new insights on cancer prognosis. This study reviews
      the approaches of molecular epidemiology in cancer research, stressing case
      control and cohort designs involving genetic polymorphisms, and factors that
      could introduce bias and confounding in these studies. Similarly to classical
      epidemiological research, genetic polymorphisms requires considering aspects of
      precision and accuracy in the study design.

PMID- 15997329
TI  - [Proliferation of paradigmatic ruptures: the case of evidence-based medicine].
AB  - The present study describes the phenomenon of paradigmatic ruptures proliferation
      in the biomedical literature. The current distortion is discussed, which has
      conferred in the last decades an opposite meaning to the term originally proposed
      by Thomas Khun. In most part, it is realized that pseudo-ruptures refer to
      technical details associated to specific contexts. It is pointed out the case of
      evidence- based medicine (EBM), proclaimed as one of these paradigmatic ruptures,
      but which essentially corroborates old concepts. Some conceptual errors are
      stressed as well as attempts to apply EBM assumptions to phenomena associated to
      subjectivity and social dynamics and other particular study subjects of social
      sciences. Twelve inconclusive meta-analyses are described to exemplify the
      paradoxes emerging from this approach. The criticism to some EBM features is
      summarized through the effects of epistemological bafflement, producing
      conceptual inaccuracies of the term; the defensive effect to which other
      disciplines are induced for not being adequate to such rationality; and the
      tendency of universal understanding of phenomena through the perspective of
      randomized double-blind studies.

PMID- 15997330
TI  - [Qualitative and quantitative methods in health: definitions, differences and
      research subjects].
AB  - The interest and accomplishments in qualitative research have been increasing in
      health. As a consequence, there is a greater demand for both institutional
      research programs and scientific journal publications. This article has the
      following purposes: (a) to present some definitions in qualitative methods used
      in Humanities and Health; (b) to compare them to the usual quantitative methods
      of health sciences; and, finally, (c) to illustrate the subject with the most
      important constructs in these methodological fields. Above all, the author's
      scope was to provide criteria to evaluate the pertinence of the path taken by
      qualitative researchers, from research plan elaboration to result interpretation.

PMID- 15997331
TI  - [Food borne intoxication and infection by Salmonella in a scientific meeting, Sao
      Paulo, 2004].

PMID- 15997335
TI  - Symbiotic Chlorella sp. of the ciliate Paramecium bursaria do not prevent
      acidification and lysosomal fusion of host digestive vacuoles during infection.
AB  - Each symbiotic Chlorella sp. of the ciliate Paramecium bursaria is enclosed in a
      perialgal vacuole derived from the host digestive vacuole, and thereby the alga
      is protected from digestion by lysosomal fusion. Algae-free cells can be
      reinfected with algae isolated from algae-bearing cells by ingestion into
      digestive vacuoles. To examine the timing of acidification and lysosomal fusion
      of the digestive vacuoles and of algal escape from the digestive vacuole, algae
      free cells were mixed with isolated algae or yeast cells stained with pH
      indicator dyes at 25+/-1 degrees C for 1.5 min, washed, chased, and fixed at
      various time points. Acidification of the vacuoles and digestion of Chlorella sp.
      began at 0.5 and 2 min after mixing, respectively. All single green Chlorella sp.
      that had been present in the host cytoplasm before 0.5 h after mixing were
      digested by 0.5 h. At 1 h after mixing, however, single green algae reappeared in
      the host cytoplasm, arising from those digestive vacuoles containing both
      nondigested and partially digested algae, and the percentage of such cells
      increased to about 40% at 3 h. At 48 h, the single green algae began to multiply
      by cell division, indicating that these algae had succeeded in establishing
      endosymbiosis. In contrast to previously published studies, our data show that an
      alga can successfully escape from the host's digestive vacuole after acidosomal
      and lysosomal fusion with the vacuole has occurred, in order to produce
      endosymbiosis.

PMID- 15997336
TI  - Localisation of fucoxanthin chlorophyll a/c-binding polypeptides of the centric
      diatom Cyclotella cryptica by immuno-electron microscopy.
AB  - Antisera were raised against the C termini of three fucoxanthin chlorophyll a/c
      binding polypeptides, Fcp2, Fcp4, and Fcp6, of the centric diatom Cyclotella
      cryptica. Immunogold electron microscopy of ultrathin-sectioned cells indicated
      that Fcp2 and Fcp4 are present in almost the same amounts, whereas approximately
      8- to 10-fold less gold label was registered for Fcp6. Immunogold electron
      microscopy of freeze-fracture replicas of thylakoid membranes showed that the C
      termini of at least Fcp2 and Fcp4 were located in the thylakoid lumen, thus
      demonstrating a 3-dimensional structure similar to that already described for the
      chlorophyll a/b-binding light-harvesting polypeptides of higher plants.

PMID- 15997337
TI  - Distribution of chlorophyll-bearing organelles in the shoot apex of a range of
      dicotyledonous plants.
AB  - Confocal laser scanning microscopy was used to study the distribution of the
      smallest detectable autofluorescing, chlorophyll-bearing structures in fresh, 40
      microm thick longitudinal sections of the shoot apex of four dicotyledonous
      plants (Arabidopsis thaliana, Nicotiana glauca, Lupinus alba, and Spinacia
      oleracea). In all species, the smallest chlorophyll-bearing particles were found
      in the outermost cell layers (L1 and L2) of the shoot apex. Their distribution
      between these layers differed in each species. The smallest such particles were
      about 0.5-1.0 microm in maximum dimension, approximating the size of a single
      granum in the developing leaf. Their size and abundance increased with increasing
      cell age and distance from the peak of the apex. Immediately beneath the L1 and
      L2 layers was a zone largely devoid of these particles. Below this nonfluorescing
      zone, in the region where the derivatives of the meristematic zone differentiate
      into cells of the central pith region, the size and abundance of the chlorophyll
      bearing particles increased progressively with increasing distance from the
      nonfluorescing zone. The presence of these small autofluorescing particles in the
      L1 and L2 cell layers of the shoot apex places the development of photosystem II
      fluorescence at an earlier stage of leaf development than previously observed.
      The use of confocal laser scanning microscopy to study unfixed sections provides
      another useful metabolic marker for mapping patterns of differentiation and
      development in the cells of the shoot apex.

PMID- 15997338
TI  - Polymer confinement and bacterial gliding motility.
AB  - Cyanobacteria and myxobacteria use slime secretion for gliding motility over
      surfaces. The slime is produced by the nozzle-like pores located on the bacteria
      surface. To understand the mechanism of gliding motion and its relation to slime
      polymerization, we have performed molecular dynamics simulations of a molecular
      nozzle with growing inside polymer chains. These simulations show that the
      compression of polymer chains inside the nozzle is a driving force for
      propulsion. There is a linear relationship between the average nozzle velocity
      and the chain polymerization rate with a proportionality coefficient dependent on
      the geometric characteristics of the nozzle such as its length and friction
      coefficient. This minimal model of the molecular engine was used to explain the
      gliding motion of bacteria over surfaces.

PMID- 15997339
TI  - Crack motion in viscoelastic solids: the role of the flash temperature.
AB  - We present a simple theory of crack propagation in viscoelastic solids. We
      calculate the energy per unit area, G(v), to propagate a crack, as a function of
      the crack tip velocity v. Our study includes the non-uniform temperature
      distribution (flash temperature) in the vicinity of the crack tip, which has a
      profound influence on G(v). At very low crack tip velocities, the heat produced
      at the crack tip can diffuse away, resulting in very small temperature increase:
      in this "low-speed" regime the flash temperature effect is unimportant. However,
      because of the low heat conductivity of rubber-like materials, already at
      moderate crack tip velocities a very large temperature increase (of order of 1000
      K) can occur close to the crack tip. We show that this will drastically affect
      the viscoelastic energy dissipation close to the crack tip, resulting in a "hot
      crack" propagation regime. The transition between the low-speed regime and the
      hot-crack regime is very abrupt, which may result in unstable crack motion, e.g.
      stick-slip motion or catastrophic failure, as observed in some experiments. In
      addition, the high crack tip temperature may result in significant thermal
      decomposition within the heated region, resulting in a liquid-like region in the
      vicinity of the crack tip. This may explain the change in surface morphology
      (from rough to smooth surfaces) which is observed as the crack tip velocity is
      increased above the instability threshold.

PMID- 15997340
TI  - Neuroprotection by extract of Petasites japonicus leaves, a traditional
      vegetable, against oxidative stress in brain of mice challenged with kainic acid.
AB  - BACKGROUND: Reactive oxygen radicals have been implicated in the pathophysiology
      of many neurologic disorders and brain dysfunctions. Kainic acid has been used as
      a model agent for the study of neurotoxicity of various excitatory amino acids,
      since it induces neuronal damage through excessive production of reactive oxygen
      species. Petasites japonicus MAX (butterbur), cultivated as culinary vegetables
      in Eastern Asia, contains various kinds of phenolic compounds as well as
      sesquiterpenes, such as petasin. In European countries, the extracts from roots
      of Petasites species have been used in the therapy of headache or asthma. AIM OF
      THE STUDY: The objective of our study is to examine the neuroprotective action of
      the Petasites japonicus MAX (butterbur) extract against oxidative damage in the
      brain of mice treated with kainic acid. METHODS: Male ICR mice, 6-8 weeks of age,
      were administered orally the butanol fraction from methanol extract of Petasites
      japonicus (BMP) or its subfraction (BMP-I or BMP-II) for 5 consecutive days.
      Thirty min after the final administration, the animals were challenged s. c. with
      kainic acid (45 mg/kg), and neurobehavioral activities were monitored. In
      addition, biomarkers of oxidative stress and neuronal loss in the hippocampus for
      the biochemical, neurobehavioral,morphological evaluations were analyzed 2 days
      after the kainic acid challenge. RESULTS: During 5-day treatment with BMP or BMP
      1, the body weight gain was not significantly different from that of vehicle-
      treated control animals. Administration of kainic acid alone induced severe
      epileptiform seizures, causing a lethality of approximately 50%, and injuries of
      pyramidal cells in the hippocampus of mice which survived the challenge. Kainic
      acid exposure also resulted in a remarkable decrease in total glutathione level
      and glutathione peroxidase activity, and an increase in the thiobarbituric acid
      reactive substance (TBARS) value in brain tissues. In comparison,
      coadministration with BMP (400 mg/kg) reduced the 54% lethality of mice,
      administered with kainic acid alone, to 25 % (P <0.05). Moreover, BMP at the same
      dose restored the levels of reduced glutathione and TBARS to control values (P
      <0.05). In further studies, BMP-I (200 mg/kg) ameliorated significantly (P <0.05)
      the kainic acid-induced behavioral signs, such as seizure activity, and all mice
      administered with BMP-I (200 mg/kg) survived the kainic acid toxicity. Consistent
      with the above, the administration with BMP-1 remarkably attenuated the
      neurobehavioral signs and neuronal loss in hippocampal CA1 and CA3 regions.
      CONCLUSION: On the basis of these results, the butanol fraction, especially BMP
      I, of Petasites japonicus MAX extract is possibly suggested to be a functional
      agent to prevent oxidative damage in the brain of mice.

PMID- 15997341
TI  - Lipomatous hypertrophy of the interatrial septum. Diagnosis by cardiac magnetic
      resonance imaging.

PMID- 15997342
TI  - Reconstruction of bicuspid aortic valves. Surgical tool or toy?

PMID- 15997343
TI  - Bicuspid aortic valve.

PMID- 15997344
TI  - Echocardiographic and hemodynamic characteristics of reconstructed bicuspid
      aortic valves at rest and exercise.
AB  - Repair of diseased bicuspid aortic valves has gained increasing interest as an
      alternative to conventional valve replacement. Hemodynamic data at exercise have
      not been reported before. The aim of this study was to investigate the clinical
      and echocardiographic status of patients after bicuspid aortic valve repair at
      rest and exercise. Between 03/94 and 09/02 a reconstruction of an incompetent
      bicuspid aortic valve was performed in 25 patients (mean age 35+/-12.1 years,
      group A, mean insufficiency 2.8 preoperatively). Patients were investigated
      clinically and echocardiographically after 2.1+/-2.4 (0.1-8.9) years at rest and
      exercise and compared to 20 controls (group B). Clinical followup was complete.
      There were no deaths, reoperations, thromboembolic or bleeding complications. At
      last examination 21 patients were in NYHA class I, n=4 in NYHA class II and mean
      aortic valve insufficiency (AI) was 1.0 with one patient having an AI>II degrees.
      Maximum and mean pressure gradient (dPmax/mean) across the aortic valve at rest
      were 14+/-5.5/7+/-2.6 mmHg for patients of group A and 7+/-2.5/3.6+/-1.1 mmHg in
      group B. Mean AVA at rest was 2.6+/-0.8 (group A) vs 2.9+/-0.6 cm(2) (group B,
      p=0.025), valvular resistance 13.4+/-4.8 (group A) vs 13.6+/-2.9 dyn x s x cm(-5)
      (group B, p>0.05). All individuals were stressed up to 100 W (dPmax/mean 21+/
      6.8/11+/-3.6, group A vs 11+/-2.9/6+/-1.3 mmHg, group B). 56% of group A and 85%
      of group B could be stressed up to 175 W with dPmax/mean 24.5+/-8.3/12+/-4.2 and
      16+/-3.6/8+/-1.4 mmHg, respectively (p<0. 01). Heart rate and blood pressure
      behavior were comparable. Left ventricular mass regression (preoperatively
      369.3+/-76.4 vs 277.3+/-80.7 g at last examination, p<0.01) was significant in
      group A but did not reach normal values (group B, 227.8+/-71.1; p<0.01). Bicuspid
      aortic valve reconstruction reduces left ventricular volume load significantly.
      Although residual mild subclinical obstruction and incompetence were observed,
      the behavior of hemodynamics at exercise was comparable to controls. The clinical
      relevance of these findings in long term follow-up has to be evaluated.

PMID- 15997346
TI  - Substrate-modification using electroanatomical mapping in sinus rhythm to treat
      ventricular tachycardia in patients with ischemic cardiomyopathy.
AB  - The treatment especially of frequent ischemic VT remains a challenge for medical
      and catheter ablation procedures. We evaluated the efficacy of a substrate-based
      procedure to eliminate clinical VTs in this patient collective. METHODS: In 25
      consecutive patients (ejection fraction 37+/-12%) with frequent symptomatic
      medically refractory ischemic VT (with recurrent ICD-shocks), left ventricular
      anatomic scar mapping (Biosense Webster CARTO) was performed in order to modify
      the underlying myocardial substrate. Scar tissue was identified as having bipolar
      voltages <0.5 mV. Prior to the procedure an electrophysiological study (EPS) to
      determine number and morphology of inducible VTs was performed. Linear ablation
      procedures (8 mm tip, 70 Watts, 70 degrees C) were based on the findings of scar
      areas and proximity to anatomic obstacles. Correct location of ablation was
      documented by similarity of the morphology during pace-mapping. Follow-up
      included clinical evaluation, ICD holter interrogation plus holter ECG recording.
      RESULTS: The clinical VT was eliminated by linear catheter ablation in 23/25
      patients (92%) (failure due to unstable catheter position during transaortic
      approach in 1 and epicardial origin of VT in 1). In 16/23 patients (70%) complete
      success could be produced with no VT inducible after substrate modification
      (1.7+/-1.0 lines per patient). In 7 patients (30%) only partial success was
      documented with further VTs inducible after ablation. No procedure-related
      complications occurred. During follow- up (10+/-4 months) 4 patients (16%) had
      occurrences of new VTs documented on ICD holter (3 patients with initially
      partial success and 1 with initial complete success) differing in cycle length
      and morphology from the clinical VT. Comparing patients with complete to those
      with partial success, there was a statistically significant difference of 93 vs.
      48% freedom of arrhythmia (p=0.03). No difference in regard to baseline
      characteristics existed in these two patient subgroups. CONCLUSIONS: Ablation of
      frequent VTs in patients with ischemic cardiomyopathy can be safely performed
      using electro-anatomic scar mapping with a high procedural success of 90%. Based
      on the morphological findings, linear ablation can suppress inducibility of all
      VTs in 70% of patients with high mid-term efficacy. In patients with only partial
      ablation success, non-clinical VTs often occur early during follow-up (50%).

PMID- 15997347
TI  - Home Monitoring in an ICD patient with incessant ventricular tachycardia.
AB  - Due to the increasing number of patients and complexity of modern tachycardia
      devices, efficient therapy surveillance as offered by Home Monitoring (HM) is of
      increasing importance. We report of an ICD patient with incessant ventricular
      tachycardia, in whom immediate arrhythmia transmission by HM permitted
      hospitalization and change of medication without time delay.

PMID- 15997345
TI  - Comparative study of tacrolimus and paclitaxel stent coating in the porcine
      coronary model.
AB  - BACKGROUND: Tacrolimus is a potent antiproliferative and immunosuppressive agent
      allowing for improved endothelial regeneration. The aim of our study was the
      preclinical evaluation of tacrolimus in a drug eluting nonerodable polymer stent
      system and its comparison with paclitaxel. METHODS AND RESULTS: A total of 40
      domestic pigs and 10 mini-pigs underwent coronary stenting with a follow-up time
      between 6 hours and 3 months. Stents were implanted in coronary arteries with an
      overstretch ratio of 1.2. After 3 days, a 1.73 microg/mm(2) coating produced
      tacrolimus tissue levels of 20 mumol/l in the coronary artery wall. Effective
      tissue concentrations were sustained for 28 days. Based on histomorphometric
      analysis, tacrolimus stent treated vessels had a reduced extent of neointima
      formation compared with controls at 28 days (-51% compared to control) but not at
      3 months. High dose paclitaxel stent coating (1.44 microg/mm(2)) was complicated
      by unexpected deaths of pigs and thrombotic stent occlusion at control
      angiography. Long-term porcine data showed no persistent inhibition of neointimal
      growth by paclitaxel and tacrolimus stent coating. CONCLUSIONS: Similar to
      paclitaxel, tacrolimus stent coating reduces neointimal proliferation in the
      porcine coronary model. However, dosing and long-term efficacy remains a critical
      issue in stent-based local drug delivery.

PMID- 15997348
TI  - Midwall myocardial fibrosis in Becker-Kiener muscular dystrophy.
AB  - We report on a 38- year-old man with Becker-Kiener muscular dystrophy (BMD) and
      dilated cardiomyopathy without clinical symptoms of congestive heart failure who
      was referred for risk evaluation of sudden cardiac death. The degree of cardiac
      involvement in BMD varies greatly from no or hardly any cardiac abnormality to
      severe arrhythmias, dilatative cardiomyopathy and heart failure to heart
      transplantation or sudden cardiac death. These cardiac abnormalities have been
      related to replacement of the cardiomyocytes by connecting tissue or fat. In the
      clinical setting, cardiovascular magnetic resonance (CMR) has been proved to be a
      valid non-invasive method for obtaining anatomical and structural information of
      the heart. Furthermore, gadolinium-enhanced CMR can also characterize areas of
      myocardial fibrosis. Demonstration of extensive areas of fibrosis in an early
      stage of the disease might be a surrogate marker for an impaired clinical
      outcome. Therefore, serial CMR examinations starting upon diagnosis of the
      disease should be considered, as this may lead to an earlier recognition of
      cardiac involvement and may affect further management of the patient.

PMID- 15997349
TI  - Recanalisation of bilateral superior vena cava after total cavopulmonary
      connection. Interventional occlusion with the Amplatzer VSD Occluder.
AB  - Formation of systemic to pulmonary venous or systemic venous left atrial
      collaterals frequently occurs in patients after Glenn or Fontan-type operations.
      Embolization with detachable metal coils is the therapy of choice for the closure
      of small vessels. These devices however are not appropriate for the occlusion of
      large collaterals, e. g. recanalized bilateral caval veins. We report two
      patients who presented late after Fontan-type operations with a gradual decrease
      in oxygen saturation due to recanalisation of bilateral caval veins.
      Interventional closure of these large veins was carried out successfully with the
      use of 8 mm Amplatzer muscular VSD Occluders, resulting in an increase of
      arterial oxygen saturations. CONCLUSION: The closure of recanalized bilateral
      superior caval veins after Fontan procedures is possible without technical
      problems by means of the Amplatzer muscular VSD Occluder. In order to avoid
      future formation of venous collaterals via the azygos or hemiazgos system, the
      occluder should be placed in the vena cava below the orifice of the azygos/
      hemiazygos vein.

PMID- 15997350
TI  - Thromboembolic cerebral ischaemic attack complicating cardiac catheterization.
      Successful local thrombolytic therapy with reduced dose rt-PA.
AB  - Cerebral ischaemia caused by thromboembolism is a possible complication of
      diagnostic and interventional cardiac catheterization. In this case report we
      describe the diagnostic steps and successful treatment strategy in the management
      of a patient who suffered from cerebral ischaemia during cardiac catheterization.
      Initial CT scanning to exclude cerebral haemorrhage was followed by angiography
      through the cardiac catheterization sheath in the right femoral artery. Occlusion
      just before the intracranial bifurcation of the right internal carotid artery was
      found and local thrombolysis given with a reduced dose of 34 mg rt-PA. The
      subsequent angiogram showed restored perfusion in the affected vessel after
      completion of thrombolytic therapy and resolution of neurological symptoms.

PMID- 15997352
TI  - [Early defibrillation through automatic defibrillation techniques and clinics:
      what have we achieved ? What do we now want to accomplish?].

PMID- 15997353
TI  - [Epidemiology of sudden cardiac death].
AB  - Sudden cardiac death remains a major challenge that we are still facing today.
      The complexity of the trigger mechanisms makes it difficult to achieve a reliable
      identification of high-risk patients. Three suggestions are made that might help
      to overcome this epidemiological catastrophe "Sudden Cardiac Death". 1. In
      patients with known heart disease risk stratification has to be improved by
      developing new methods to identify specifically those individuals, who are at
      risk for sudden rather than non-sudden cardiac death. 2. The general population
      contains an unknown proportion of individuals with advanced coronary disease,
      which is commonly asymptomatic. In these so called "normal population" classical
      risk stratification does not work. However, since there is a close relationship
      between the prevalence of risk factors for coronary disease and sudden death, a
      consequent treatment of risk factors should have a positive effect on sudden
      death rate as well. 3. The success rate of resuscitation has to be improved by
      strengthening each single link of the "chain of survival". Laypersons trained in
      basic and advanced life support techniques have to play a much major role on this
      scene.

PMID- 15997354
TI  - [Resuscitation in ventricular fibrillation: what is essential?].
AB  - Prognosis of prehospital cardiac arrest due to ventricular fibrillation is
      dependent on the first minutes, as survival decreases by 10% for each minute by
      which resuscitation attempts are delayed. Thus, early defibrillation plays a key
      role in improving outcome of cardiac arrest victims. The effectiveness of
      automated external defibrillators (AEDs) in this setting has been proven by
      several clinical trials. There remains controversy with regard to using AEDs in
      the in-hospital setting, as well as the approach of "public access"
      defibrillation. Whereas the use of intravenous antiarrhythmic drugs, particularly
      amiodarone, remains controversial, new data support the use of vasopressine
      instead of epinephrine as vasopressor drug in cardiac arrest patients. The
      present review aims to focus on the above mentioned aspects as well as on the
      changes to the present ILCOR guidelines which have led to modification of the
      resuscitation guidelines of the European Resuscitation Council (ERC).

PMID- 15997355
TI  - [Technical requirements for early defibrillation: what are the capabilities of
      automated external defibrillators].
AB  - Modern automated external defibrillators (AEDs) offer a variety of technical
      improvements which increase the efficacy of early defibrillation, facilitate the
      application by not or minimally trained persons and improve safety. The
      development of biphasic shocks allows better myocardial protection, the use of
      lithium batteries, and a marked decrease of AEDs, in size. Microprocessors
      realize complex acoustic and visual prompts which lead the user through all steps
      of cardiopulmonary resuscitation (CPR) according to current guidelines. The
      design of AEDs has been simplified; many devices provide only a single button
      which can be used for all active processes. Memory functions record the whole CPR
      with all details which can be transferred to other computers and analyzed off
      line. The introduction of AEDs has reduced the delay between collapse and
      defibrillation to less than 4 min in several studies thus increasing the success
      of CPR and the proportion of patients dismissed from hospital alive and without
      neurological deficit. Up to 93% of untrained volunteers were able to successfully
      complete defibrillation with the use of an AED, sixth-form pupils without
      experience in CPR were only few sec slower with an AED than staff of emergency
      medical services. The ability to perform CPR after defibrillation guided by the
      AED depends primarily on the clarity of acoustic prompts which have to consider
      the terms and abbreviations of the respective language. Currently available AEDs
      surpass performance goals of the AHA. However, all devices exhibit advantages and
      disadvantages which will be discussed in this review.

PMID- 15997356
TI  - [First responder defibrillation in the USA, Europe and Germany--prerequisites,
      experiences, perspectives].
AB  - Sudden out-of-hospital cardiac arrest is a leading cause of death and only 5-8%
      of patients survive such event. Defibrillation is the mose effective treatment
      and should performed within 5 minutes; however, its effectiveness diminishes with
      each passing minute. "Early defibrillation" is the use of automated external
      defibrillators (AEDs) by trained public-safety personnal ("first responder"),
      whereas "public access" defibrillation describes AED use by persons who have no
      specific AED training. Several studies in the US and in Europe show that first
      responder defibrillation will increase the number of survivors of out-of-hospital
      cardiac arrest compared to paramedics. This is caused by a shorter "call-to
      arrival-time" in first responders compared to paramedics. In Europe, programs for
      the use of automated external defibrillators exist only occasionally. Reasons for
      this are the lack of open-mindedness, logistic and legal problems. In Germany,
      there are only few AED programs with promising results. At the present time,
      placement of automated external defibrillators in public places frequented by a
      large number of susceptible people will increase overall survival. However,
      placement of AEDs in all public places is still debatable and further studies are
      necessary to estimate the potential impact of publicc access defibrillators.

PMID- 15997357
TI  - [First responder defibrillation in the LAGO-die Therme--results and experiences].
AB  - The use of automated external defibrillator (AED) by persons other than
      paramedics and emergency medical technicians is advocated by several US- and
      European organizations. However, at the present time it is still unclear to
      identify public places with a high incidence of out-of-hospital cardiac arrest.
      There are few data on the potential impact of public access defibrillators on
      survival after out-of-hospital cardiac arrest in sporting arenas or water parks.
      Therefore, we studied prospectively incidence of out-of-hospital cardiac arrest
      in the LAGO-die Therme in Herne. This is one of the most important swimming parks
      in Europe and member of the European Waterpark Association EWA. Eight AEDs were
      placed in the waterpark LAGO-die Therme. The locations where the defibrillators
      were stored were chosen to make possible a target interval of 60 seconds from
      collapse to first defibrillation. Twenty waterpark officers were instructed in
      cardiopulmonary resuscitation and in the use of the AED. During November 16, 2001
      and December 31, 2004, 2.05 Mio. visitors were counted in the LAGO. Out-of
      hospital cardiac arrest occurred in none of them. AED were used in two visitors
      with non arrhythmogenic syncope, no shock was delivered. Questionaires were done
      in 588 visitors (336 males, 252 females, mean age 38+21 years) in 2002 and in 579
      visitors (322 males, 257 females, mean age 37+/-25 years) in 2004. In 2002, 77%
      of the visitors noticed the AED and, therefore, 49% performed more sporting
      activities. In addition, in 2004, AED was noticed by 480 visitors (83%) and 277
      visitors (48%) did more sporting activities. There were no significant
      differences between 2002 and 2004 (p=ns). Despite no out-of-hospital cardiac
      arrest in the waterpark during the 3 year follow- up, it seems reasonable to
      install AED in sporting places with thousands of visitors per year.

PMID- 15997358
TI  - [Automated external defibrillators: perspectives and outlook].
AB  - In Germany about 80.000 patients die of sudden cardiac death each year with
      enormous human, social and economic consequences. Most cases of sudden cardiac
      death are caused by ischemia-triggered ventricular fibrillation. A precondition
      for survival of the victims is an optimally and fast reacting "chain of
      survival". One of the central links of this chain is timely defibrillation, which
      is the only effective therapy for treatment of ventricular fibrillation.
      Automated external defibrillators proved to be a major step forward in
      improvement of resuscitation results. It has been convincingly demonstrated, that
      these devices not only are safe and efficacious in the hands of rescue personnel
      of different qualification degrees but also in the hands of minimally trained
      "first responders" and even in the hands of untrained lay people. This story of
      success was paralleled by the development of a new generation of biphasic
      defibrillators, which have a superior efficacy, are lightweight and are even
      cheaper than conventional devices. It must however kept in mind, that progress
      offered by these new opportunities will only translate in better resuscitation
      results, when programmes are thoroughly planned, will stay under continuous
      quality control with regard to performance of devices and rescuers and if new
      knowledge in resuscitation is adequately incorporated in action protocols.

PMID- 15997360
TI  - [Pacemaker-ekg-quiz].

PMID- 15997359
TI  - [Position paper on "Automatic external defibrillation"].

PMID- 15997363
TI  - Intestinal vaginoplasty: is it optimal treatment of vaginal agenesis? A pilot
      study. Surgical method of sigmoid colon vaginoplasty in vaginal agenesis.
AB  - The outcome of 11 cases with vaginal agenesis who underwent intestinal
      vaginoplasties are presented. Patients were between 18 and 37 years old. Ileum
      vaginoplasty and sigmoid colon vaginoplasty were carried out in two and nine
      cases, respectively. Ileum necrosis at donor site requiring ileum resection and
      bilateral ileostomy encountered in one of the cases was the major complication.
      Mild stenosis responsive to finger dilatation had been detected in two women with
      sigmoid vaginoplasty. Excess mucous production, long operation time, and
      shortness of mesentery of ileum led us to abandon ileum vaginoplasty, and sigmoid
      colon vaginoplasty was performed in the following cases with vaginal agenesis.
      All of the neovaginas were patent and functional. We suggest sigmoid colon
      vaginoplasty as the treatment of choice because of its large lumen, thick walls
      resistant to trauma, adequate secretion allowing lubrication, not necessitating
      prolonged dilatation, short recovery time compared with ileum vaginoplasties; and
      in patients reluctance to prolonged use of dilatators or in those who experienced
      previous failure of the other treatment modalities.

PMID- 15997364
TI  - Laparoscopic uterosacral ligament uterine suspension compared with vaginal
      hysterectomy with vaginal vault suspension for uterovaginal prolapse.
AB  - This study compares the outcomes of laparoscopic uterosacral ligament uterine
      suspension (LUSUS) to those of vaginal vault suspension with total vaginal
      hysterectomy (TVH) for the treatment of symptomatic uterovaginal prolapse. We
      compared the outcomes of 25 LUSUS to those of 25 TVH with vaginal vault
      suspension among age-matched controls. No significant complications occurred in
      either group. EBL and hospitalization duration were significantly less in LUSUS
      patients (72 cc vs. 227 cc, P < .0001 and 1.05 vs. 1.65 days, P = .002). Vault
      support, as measured by postoperative pelvic organ prolapse quantitation system
      point D in the LUSUS group and point C in the TVH group, was better for the LUSUS
      group (D = -9 vs. C = -7.6, P = .002). No LUSUS group patient underwent
      reoperation for recurrent apical prolapse as compared to three TVH patients.
      LUSUS is an effective treatment for appropriately selected women with
      uterovaginal prolapse who desire uterine preservation.

PMID- 15997366
TI  - Fractional anisotropy and mean diffusivity measurements on normal human brain:
      comparison between low-and high-resolution diffusion tensor imaging sequences.
AB  - Non-invasive in vivo visualization of white matter fiber tracts is currently
      feasible by means of diffusion tensor imaging (DTI) techniques. DTI-derived
      metrics, like fractional anisotropy (FA) and mean diffusivity (MD), have the
      potential to improve tissue characterization. Technical optimization of diffusion
      tensor sequences, including signal-to-noise ratio and spatial resolution, was
      performed for 20 normal subjects. High- and low-resolution DTI sequences were
      applied on all subjects and FA, MD parametric maps were reconstructed for both
      protocols. Voxel-based statistical analysis revealed regions with significantly
      different FA and MD values between the two sequences, while the same type of
      analysis was performed to illustrate regions with significantly different signal
      to-noise ratio. In conclusion, optimized DTI sequences may be applied routinely
      in clinical practice with a standard MR scanner, while accurate quantification of
      FA and MD may improve lesion characterization.

PMID- 15997365
TI  - Molecular phylogeny of coral-reef sea cucumbers (Holothuriidae: Aspidochirotida)
      based on 16S mitochondrial ribosomal DNA sequence.
AB  - Members of the Holothuriidae, found globally at low to middle latitudes, are
      often a dominant component of Indo-West Pacific coral reefs. We present the first
      phylogeny of the group, using 8 species from the 5 currently recognized genera
      and based on approximately 540 nucleotides from a polymerase chain reaction
      amplified and conserved 3' section of 16S mitochondrial ribosomal DNA. Parsimony
      and likelihood analyses returned identical topologies, permitting several robust
      inferences to be drawn. Several points corroborated the Linnean classification.
      Actinopyga and Bohadschia each appear monophyletic and Pearsonothuria is sister
      to Bohadschia. Other aspects of our phylogeny, however, were not in accord with
      the taxonomy of Holothuriidae or previous speculations about the group's
      evolutionary history. Most notably, the genus Holothuria appears paraphyletic.
      Actinopyga and Bohadschia, sometimes held to be closely related to one another
      because of certain morphologic similarities, are only distantly related. The
      morphologically distinct Labidodemas, even thought to warrant separation at the
      family level, is nested well within Holothuria. A maximum parsimony
      reconstruction of ancestral ossicle form on the phylogeny indicated that, in
      addition to a probable bout of elaboration in ossicle form (the modification of
      rods or rosettes to holothuriid-type buttons), at least 2 rounds of ossicle
      simplification also transpired in which buttons reverted to rods or rosettes.
      Cuvierian tubules, defensive organs unique to numerous members of Holothuriidae,
      were probably present before the initial radiation of the family, but the
      reconstruction is ambiguous as to their ancestral function.

PMID- 15997367
TI  - Cost analysis of procedures related to the management of renal artery stenosis
      from various perspectives.
AB  - To determine the costs associated with the diagnostic work-up and percutaneous
      revascularization of renal artery stenosis from various perspectives. A
      prospective multicenter comparative study was conducted between 1998 and 2001. A
      total of 402 hypertensive patients with suspected renal artery stenosis were
      included. Costs were assessed of computed tomography angiography (CTA), magnetic
      resonance angiography (MRA), digital subtraction angiography (DSA), and
      percutaneous revascularization. From the societal perspective, DSA was the most
      costly (euro 1,721) and CTA the least costly diagnostic technique (euro 424). CTA
      was the least costly imaging procedure irrespective of the perspective used. The
      societal costs associated with percutaneous renal artery revascularization ranged
      from euro 2,680 to euro 6,172. Overall the radiology department incurred the
      largest proportion of the total societal costs. For the management of renal
      artery stenosis, performing the analysis from different perspectives leads to the
      same conclusion concerning the least costly diagnostic imaging and
      revascularization procedure.

PMID- 15997368
TI  - Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance
      network.
AB  - Leishmaniasis is a rare, non-notifiable disease in Germany. Epidemiological and
      clinical data, therefore, are scarce. Most infections seen in Germany are
      contracted outside the country. The German surveillance network for imported
      infectious diseases (Surveillance Importierter Infektionen in Deutschland, or
      SIPMID) recorded 42 cases of imported leishmaniasis (16 visceral, 23 cutaneous,
      and 3 mucocutaneous) from January 2001 to June 2004. Although most infections
      were acquired in European Mediterranean countries, the risk of infection was
      highest for travelers to Latin America. HIV coinfection was observed
      significantly more often in patients with visceral leishmaniasis than in patients
      with cutaneous/mucocutaneous leishmaniasis (31 vs. 4%, p=0.02). The median time
      to a definitive diagnosis was 85 days in cases of visceral leishmaniasis and 61
      days in cases of cutaneous/mucocutaneous leishmaniasis, reflecting the
      unfamiliarity of German physicians with leishmanial infections. Visceral
      leishmaniasis was treated most frequently with amphotericin B, whereas
      cutaneous/mucocutaneous leishmaniasis was treated with a variety of local and
      systemic therapies. The findings presented here should serve to increase
      awareness as well as improve clinical management of leishmaniasis in Germany.

PMID- 15997369
TI  - Sensitivity of urinary antigen test in relation to clinical severity in a large
      outbreak of Legionella pneumonia in Spain.
AB  - Presented here are the results of Legionella urinary antigen testing correlated
      with patient characteristics and severity of pneumonia (Fine score) in 295
      patients diagnosed with Legionella pneumonia in connection with a large outbreak
      in Murcia, Spain. Overall, the sensitivity of the urinary antigen test was 47.7%
      (141/295). A statistically significant association was found between the clinical
      severity of pneumonia and test sensitivity; 85.7% for patients with severe
      pneumonia versus 37.9% for patients with mild pneumonia (risk ratio, 2.3).
      Variables significantly associated with test positivity in multivariate analysis
      were as follows: pre-existing pulmonary disease, body temperature >40 degrees C,
      leukocytosis and multilobar infiltrates. Patients with mild pneumonia may go
      undiagnosed if the urinary antigen test is used alone.

PMID- 15997370
TI  - Indirect estimates of cardiac index.

PMID- 15997371
TI  - Use of a stopped-flow technique for investigation and determination of thiourea
      and its N-methyl derivatives as inducers of the iodine-azide reaction.
AB  - A stopped-flow technique has been used to investigate the behaviour of 2
      thiourea, 1-methyl-2-thiourea, 1,3-dimethyl-2-thiourea, and 1,1,3,3-tetramethyl-2
      thiourea in the induced iodine-azide reaction. This technique enables the
      progress of the reaction to be followed by monitoring the decrease in the
      absorbance of the iodine-starch complex at 595 nm. The effect of the
      concentration of the reagents on the rate of the reaction was investigated and a
      kinetic method for determination of the compounds is proposed. 2-Thiourea, 1
      methyl-2-thiourea, and 1,3-dimethyl-2-thiourea can be determined in the range 3
      75 micromol L(-1) and 1,1,3,3-tetramethyl-2-thiourea in the range 2-200 micromol
      L(-1).

PMID- 15997372
TI  - Ultra-trace analysis of platinum in human tissue samples.
AB  - Background levels of platinum were determined in human autopsy tissues taken from
      five individuals. The investigated specimens were lung, liver and kidney. Sample
      preparation involved microwave digestion followed by an open vessel treatment.
      Inductively-coupled plasma sector field mass spectrometry (ICP-SFMS) was applied
      in combination with an ultrasonic nebulization/membrane desolvation system for
      sample introduction. Isotope dilution analysis was employed for accurate
      quantification of platinum. Excellent procedural detection limits (3 s
      validation) of 20, 20 and 34 pg g(-1) dry weight were obtained for lung, liver
      and kidney tissue, respectively. Due to the lack of appropriate biological
      reference material, road dust (BCR-723) was used for method validation. Platinum
      levels ranging between 0.03 and 1.42 ng g(-1) were determined in the investigated
      samples. The platinum concentrations observed in human lung tissue may reflect
      the increasing atmospheric background levels of platinum originating from car
      catalysts. The presence of platinum in kidney and liver tissue samples clearly
      indicates the bioavailability of the element.

PMID- 15997373
TI  - Combination of gel electrophoresis and ICP-mass spectrometry-novel strategies for
      phosphoprotein measurement.
AB  - The potential for developing improved procedures for phosphate measurement
      through combinations of gel electrophoresis and quadrupole-based ICP mass
      spectrometry utilising (47)PO(+) is investigated. Laser ablation of gels offers a
      rapid and direct quantitation route, but is subject to high blanks due to P
      impurities in gels and associated reagents; nevertheless optimisation of laser
      sampling afforded improved method sensitivity (limit of detection 0.09 microg g(
      1)). Implementation of whole gel elution (WGE) with FI-ICP-MS (conventional
      solution nebulisation) following gel electrophoresis permitted quantitation at
      the sub microg l(-1) level, and microcolumn processing (activated alumina) was
      effective at rejecting phosphate contamination. The potential for S-induced
      molecular ion interference at mass 47 was demonstrated.

PMID- 15997374
TI  - Combined LIBD and XAFS investigation of the formation and structure of Zr(IV)
      colloids.
AB  - The solubility of Zr(OH)4(am)--in other words hydrated Zr(IV) oxyhydroxide--is
      determined by means of coulometric titration (CT), and colloids are detected by
      laser-induced breakdown when the solubility limit is exceeded. Our results at pH
      3-8 demonstrate that the solubility of Zr(OH)4(am) is several orders of magnitude
      higher than reported classical solubility data for acidic solutions, determined
      from undersaturation with a less soluble microcrystalline Zr(IV) oxide
      precipitate. Analysis of extended X-ray absorption fine structure (EXAFS) data
      shows that the microcrystalline colloids in a 0.1 mol l(-1) Zr aqueous solution
      at pH 0.2 contain tetrameric units, similar to those present in the structure of
      ZrOCl2.8H2O. Characterization of the CT solutions by means of EXAFS shows that
      oligomeric species form as the solubility limit is approached. The current lack
      of data on equilibrium constants for polynuclear hydroxide complexes prohibits
      the use of a realistic speciation model to describe the solubility of pH
      dependent Zr(OH)4(am). However, the solubility curve is obtained using the
      mononuclear hydrolysis constants estimated in the present paper, along with the
      solubility constant (log K'sp=-49.9+/-0.5 in 0.5 mol l(-1) NaCl; log K
      degrees(sp)=-53.1+/-0.5 at I=0).

PMID- 15997375
TI  - Determination of reactive oxygen species in single human erythrocytes using
      microfluidic chip electrophoresis.
AB  - Reactive oxygen species (ROS) are known to not only mediate the damage of
      cellular constituents but also to regulate cellular signaling. Analysis of ROS is
      essential if we wish to understand the mechanisms of cellular alterations. In
      this paper, a microfluidic chip-based approach to the determination of ROS in
      single erythrocyte was developed by using a simple crossed-channel glass chip
      with integrated operational functions, including cell sampling, single cell
      loading, docking, lysing, and capillary electrophoretic (CE) separation with
      laser-induced fluorescence (LIF) detection. Non-fluorescent dihydrorhodamine 123
      (DHR 123), which can be oxidized intracellularly by ROS to the fluorescent
      rhodamine 123 (Rh 123), was used as the fluorogenic reagent. The effect of pH on
      the migration time of Rh 123 and detection sensitivity was discussed. The present
      method minimized dilution of intracellular ROS during reaction with DHR 123 and
      determination. As a result, an extremely low detection limit of 0.8 amol has been
      achieved. The time required for complete analysis of one human erythrocyte was
      less than 3 min. A migration time precision of 4.1% RSD was obtained for six
      consecutively-injected cells. Upon stimulation with 4 mmol/l H2O2 for 10 min, the
      intracellular ROS concentration was found to increase on average by about a
      factor of 8.4.

PMID- 15997377
TI  - Development of a PLS based method for determination of the quality of beers by
      use of NIR: spectral ranges and sample-introduction considerations.
AB  - Near infrared spectroscopy (NIR) has been used to determine important indicators
      of the quality of beers, for example original and real extract and alcohol
      content, using a partial least squares (PLS) calibration approach. A population
      of 43 samples, obtained commercially in Spain and including different types of
      beer, was used. Cluster hierarchical analysis was used to select calibration and
      validation data sets. Absorbance sample spectra, in transmission mode, were
      obtained in triplicate by using a 1-mm pathlength quartz flow cell and glass
      chromatography vials of 6.5 mm internal diameter. The two methods of sample
      introduction were compared critically, on the basis of spectral reproducibility
      for triplicate measurements and after careful selection of the best spectral pre
      processing and the spectral range for building the PLS model, to obtain the best
      predictive capability. For each mode of sample introduction two calibration sets
      were assayed, one based on the use of 15 samples and a second extended based on
      use of 30 samples, thus leaving 28 and 13 samples, respectively, for validation.
      The best results were obtained for 1 mm flow cell measurements. For this method
      original zero-order spectra data in the ranges 2220-2221 and 2250-2350 nm were
      chosen. For the real extract, original extract, and alcohol d(x-y) and s(x-y)
      values of -0.04 and 0.07% w/w, -0.01 and 0.13% w/w, and -0.01 and 0.1% v/v,
      respectively, were obtained. The maximum errors in the prediction of any of these
      three indicators for a new sample were 2.2, 1.2, and 1.9%, respectively. This
      method compares favorably with the automatic reference method in terms of speed,
      reagent consumed, and waste generated.

PMID- 15997378
TI  - Quantification of free and total salicylic acid in plants by solid-phase
      extraction and isocratic high-performance anion-exchange chromatography.
AB  - Salicylic acid (SA) is an important signaling compound in plants and is involved
      in various defense responses. Here we report a new method for quantification of
      free and total soluble SA in Arabidopsis thaliana with 5-fluorosalicylic acid (5
      FSA) as internal standard. The SA was isolated from leaf extracts by solid-phase
      extraction with phenyl-phase cartridges and selectively eluted as the cationic
      iron(III)-complex. Recoveries of SA and 5-FSA were equal and exceeded 90%. Free
      SA was subsequently released from the iron(III)-complex by addition of 2,2'
      bipyridyl and high-performance anion-exchange chromatography was performed on an
      NH2 column. The SA appeared as last peak with a retention time of 15 min,
      baseline-separated from other substances. On-line detection was performed
      fluorimetrically for both SA and 5-FSA at an excitation wavelength of 300 nm and
      an emission wavelength of 410 nm, because both substances give similar
      fluorescence spectra. The detection limit for SA was 5 ng g(-1) FW for a sample
      size of 100 mg. Thus the main advantages of the method are highly selective
      sample preparation, increased sensitivity, reduced analysis time compared with
      reversed-phase HPLC, and use of a novel internal standard detectable under the
      same conditions as SA. The techniques described are applicable to other plant
      materials.

PMID- 15997379
TI  - Determination of actinide speciation in solution using high-energy X-ray
      scattering.
AB  - High-energy X-ray scattering (HEXS) has been used to understand the coordination
      environment of the uranyl ion in a perchlorate solution. Assuming the two
      coordinating oxo ligands bound to U(VI) are represented in a peak in the pair
      distribution function (PDF) at 1.766(1) A, integration of the peak intensity is
      used to quantify the charge located on the oxygens. The dioxo ligands are
      essentially neutral, as predicted by numerous published calculations, with a
      charge of -16.4(8) electrons. The peak in the PDF at 2.420(1) A is consistent
      with equatorial ligating waters. The intensity of this peak is inconsistent with
      an integral coordination number and is used to propose a solution equilibrium of
      five and four waters coordinating to the uranyl(VI) ion favoring the five
      coordinate species. This equilibrium is then used to experimentally determine
      that five-coordinate uranyl is 1.19+/-0.42 kcal/mol more stable than its four
      coordinate counterpart under the conditions of the experiment. Further peaks in
      the Fourier transform of the scattering data at 4.50, 7, and 8.7 A are attributed
      to uranium-solvent correlations.

PMID- 15997380
TI  - Animal glues in mixtures of natural binding media used in artistic and historic
      objects: identification by capillary zone electrophoresis.
AB  - Animal glues were often used in historic and artistic objects, e.g. as paint
      ground, as binders for pigments, or as adhesives. The sources were egg, casein,
      or different collagens. For restoration and conservation purposes it is important
      to know which kind of animal glue a museum object contains. Capillary
      electrophoresis can deliver such information, because it enables differentiation
      among the three proteinaceous glue classes according to their different amino
      acid patterns after hydrolysis. This work deals with the most relevant problem in
      practice, whether this identification is obstructed by the presence of other
      binders, with which they are mixed in many real samples; in particular,
      interference from plant gums and drying oils was investigated. Capillary
      electrophoresis of the hydrolysates (after reaction with 6 mol L(-1) HCl) was
      performed with an acidic background electrolyte consisting of chloroacetic acid
      (51.9 mmol L(-1)) adjusted with LiOH to pH 2.26. The underivatised analytes were
      detected with a contactless conductivity detector. It was found that the
      constituents of the plant gums (monosaccharides) or drying oils (long-chain fatty
      acids and short-chain dicarboxylic acids) never interfered with identification of
      the animal glues, as shown for artificial mixtures of the different binders even
      at tenfold excess over the animal glue, and for egg tempera samples. The method
      was used to identify the filling material from a statue from the eighteenth
      century.

PMID- 15997381
TI  - Electrochemical behavior of a covalently modified glassy carbon electrode with
      aspartic acid and its use for voltammetric differentiation of dopamine and
      ascorbic acid.
AB  - Aspartic acid was covalently grafted on to a glassy carbon electrode (GCE) by
      amine cation radical formation in the electrooxidation of the amino-containing
      compound. X-ray photoelectron spectroscopic (XPS) measurement and cyclic
      voltammetric experiments proved the aspartic acid was immobilized as a monolayer
      on the GCE. Electron transfer to Fe(CN)6(4-) in solution of different pH was
      studied by cyclic voltammetry. Changes in solution pH resulted in the variation
      of the charge state of the terminal group; surface pK(a) values were estimated on
      the basis of these results. Because of electrostatic interactions between the
      negatively charged groups on the electrode surface and dopamine (DA) and ascorbic
      acid (AA), the modified electrode was used for electrochemical differentiation
      between DA and AA. The peak current for DA at the modified electrode was greatly
      enhanced and that for AA was significantly reduced, which enabled determination
      of DA in the presence of AA. The differential pulse voltammetric (DPV) peak
      current was linearly dependent on DA concentration over the range 1.8 x 10(-6)
      4.6 x 10(-4) mol L(-1) with slope (nA micromol(-1) L) and intercept (nA) of 47.6
      and 49.2, respectively. The detection limit (3delta) was 1.2 x 10(-6) mol L(-1).
      The high selectivity and sensitivity for dopamine was attributed to charge
      discrimination and analyte accumulation. The modified electrode has been used for
      determination of DA in samples, in the presence of AA, with satisfactory results.

PMID- 15997382
TI  - A sensitive and specific HPLC-MS method for the determination of sophoridine,
      sophocarpine and matrine in rabbit plasma.
AB  - A sensitive and specific method was developed for the determination of
      sophoridine (SRI), sophocarpine (SC) and matrine (MT) in rabbit plasma by HPLC
      MS. After an administration of Kuhuang by injection, blood samples were collected
      and extracted with methanol. The extract solutions were analysed by HPLC-MS
      method. The separation was performed on a ZORBAX Extend-C18 column using
      methanol/water/diethylamine (50:50:0.07, v/v/v) as mobile phase. The
      quinolizidine alkaloids were detected by using mass spectrometry in the SIM mode.
      There was a good linear relationship between peak area and concentration of
      analytes over the concentration range of 13.2-995.0 ng mL(-1) for SRI, 7.0-530.0
      ng mL(-1) for SC and 8.8-655.0 ng mL(-1) for MT, respectively. The absolute
      recovery of this method was more than 57% for SRI, 87% for SC and 91% for MT. The
      accuracy of assay was more than 90%. The limits of detection (LODs) were 6.8 ng
      mL(-1) for SRI, 3.5 ng mL(-1) for SC and 4.2 ng mL(-1) for MT, respectively. The
      limits of quantitation (LOQs) were 13.2 ng mL(-1) for SRI, 7.0 ng mL(-1) for SC
      and 8.8 ng mL(-1) for MT, respectively. The intra-day and inter-day coefficients
      of variation (RSDs) were less than 10.1, 6.3 and 5.8% for SRI, SC and MT,
      respectively. The developed method was applied to determine the concentration
      time profiles of SRI, SC and MT in rabbit plasma after injection of Kuhuang.

PMID- 15997384
TI  - [Interdisciplinary intensive medicine. Report from the Seminar Congress in
      Gamisch-Partenkirchen, 6-11 March, 2005].

PMID- 15997383
TI  - [Molecular therapy in gastroenterology and hepatology].
AB  - During recent years, molecular techniques have significantly impacted our
      understanding and therapeutic concepts in gastrointestinal and liver disease. In
      a number of diseases, diagnostic work-up includes molecular data that supplements
      the phenotypical evaluation. This includes monogenic diseases as well as the
      identification of genetic risk factors (e. g. NOD2/CARD15 mutation in Crohn's
      disease) and viral disease. Attempts to replace liver transplantation in
      hereditary liver disease by targeted molecular interventions (e. g. via viral
      vectors) are still experimental, but the associated techniques have improved
      considerably. The molecular identification of therapeutic targets was followed by
      the development of specifically tailored therapeutics. These agents are mainly
      used in the treatment of chronic inflammatory bowel disease and gastrointestinal
      tumors.

PMID- 15997385
TI  - [Rheumatology].
AB  - The advent of monoclonal antibodies for the treatment of rheumatic diseases has
      revolutionized our understanding of therapeutic efficacy. Only a few years ago,
      response rates of >70% combined with significant reductions in inflammatory
      activity and radiologic progression would have been impossible. At the same time,
      however, issues of safety and cost have gained in importance and challenge
      physicians and patients alike. Making these new drugs available to as many
      eligible patients as possible requires a thorough documentation of disease
      activity using standardized outcome measures as well as a profound knowledge of
      their safety profiles. In addition, institutional guidelines for the use of these
      agents need to be as close to the cutting edge of science as possible. The
      following article presents an overview of currently available biologic agents in
      rheumatology and a prospect of those to come.

PMID- 15997387
TI  - [Role of adrenomedullin in the pathogenesis and treatment of cardiovascular
      dysfunctions and sepsis].
AB  - Adrenomedullin (AM) is an endogenous vasodilatory peptide hormone, which plays a
      key role in the regulation and preservation of cardiovascular and pulmonary
      functions. Clinical and experimental studies have demonstrated that AM represents
      an alternative therapeutic option in the treatment of pulmonary hypertension. In
      addition, AM proved to be useful in the treatment of cardiovascular dysfunctions,
      such as arterial hypertension and congestive heart failure following myocardial
      infarction. Recent research has also shown that AM plays a pivotal role in the
      development of sepsis-associated hemodynamic and microcirculatory disorders.
      Experimental studies also suggest that infusion of exogenous AM might be a
      rational approach to prevent and treat hypodynamic septic shock. The objectives
      of this review article are to characterize the regulative properties of AM and to
      discuss clinical and experimental studies which allow to judge the role of AM in
      the setting of cardiovascular dysfunction and sepsis.

PMID- 15997389
TI  - Linkage disequilibrium in European elite maize germplasm investigated with SSRs.
AB  - Information about the extent and genomic distribution of linkage disequilibrium
      (LD) is of fundamental importance for association mapping. The main objectives of
      this study were to (1) investigate genetic diversity within germplasm groups of
      elite European maize (Zea mays L.) inbred lines, (2) examine the population
      structure of elite European maize germplasm, and (3) determine the extent and
      genomic distribution of LD between pairs of simple sequence repeat (SSR) markers.
      We examined genetic diversity and LD in a cross section of European and US elite
      breeding material comprising 147 inbred lines genotyped with 100 SSR markers. For
      gene diversity within each group, significant (P<0.05) differences existed among
      the groups. The LD was significant (P<0.05) for 49% of the SSR marker pairs in
      the 80 flint lines and for 56% of the SSR marker pairs in the 57 dent lines. The
      ratio of linked to unlinked loci in LD was 1.1 for both germplasm groups. The
      high incidence of LD suggests that the extent of LD between SSR markers should
      allow the detection of marker-phenotype associations in a genome scan. However,
      our results also indicate that a high proportion of the observed LD is generated
      by forces, such as relatedness, population stratification, and genetic drift,
      which cause a high risk of detecting false positives in association mapping.

PMID- 15997390
TI  - Application of network theory to potential mycorrhizal networks.
AB  - The concept of a common mycorrhizal network implies that the arrangement of
      plants and mycorrhizal fungi in a community shares properties with other
      networks. A network is a system of nodes connected by links. Here we apply
      network theory to mycorrhizas to determine whether the architecture of a
      potential common mycorrhizal network is random or scale-free. We analyzed
      mycorrhizal data from an oak woodland from two perspectives: the phytocentric
      view using trees as nodes and fungi as links and the mycocentric view using fungi
      as nodes and trees as links. From the phytocentric perspective, the distribution
      of potential mycorrhizal links, as measured by the number of ectomycorrhizal
      morphotypes on trees of Quercus garryana, was random with a short tail, implying
      that all the individuals of this species are more or less equal in linking to
      fungi in a potential network. From the mycocentric perspective, however, the
      distribution of plant links to fungi was scale-free, suggesting that certain
      fungus species may act as hubs with frequent connections to the network.
      Parallels exist between social networks and mycorrhizas that suggest future lines
      of study on mycorrhizal networks.

PMID- 15997388
TI  - [Effects of dopamine on cellular and humoral immune responses in septic
      patients].
AB  - In vitro and in vivo studies have demonstrated that apart from its hemodynamic
      action dopamine can modulate immune responses. Dopamine reduces the synthesis of
      proinflammatory and induces the synthesis of anti-inflammatory mediators.
      Dopamine inhibits neurohormone synthesis, lymphocyte proliferation and platelet
      aggregation. It reduces the phagocytic activity of neutrophils and induces
      apoptosis. Particularly with regard to sepsis, where high serum dopamine levels
      are reached by enhanced endogenous production, exogenous application and impaired
      clearance, this immunomodulation may have a clinical impact. This review
      summarizes dopamine-mediated immunomodulating effects to advance the knowledge
      regarding dopamine as an immune regulator under septic conditions.

PMID- 15997391
TI  - Posterior reversible encephalopathy syndrome: a possible late interaction between
      cytotoxic agents and general anaesthesia.
AB  - A 49-year-old woman who had previously received treatment with cytotoxic drugs
      for metastatic gestational trophoblastic disease (GTD) presented with a witnessed
      tonic-clonic seizure, headache, confusion and blindness, 6 days after the
      uneventful administration of a general anaesthetic and 2 months after cessation
      of chemotherapy. Magnetic resonance imaging showed relatively symmetrical,
      subcortical, white matter abnormalities, predominantly affecting the occipital,
      posterior temporal and parietal lobes and the cerebellum. T2-dependent
      abnormalities and elevated regional apparent diffusion coefficient were present
      in a pattern typical for posterior reversible encephalopathy syndrome (PRES). The
      clinical and radiological manifestations were resolved completely with supportive
      therapy. This case of PRES may be a late complication of gemcitabine or cisplatin
      therapy precipitated by a general anaesthetic, or associated electrolyte or blood
      pressure disturbance.

PMID- 15997392
TI  - Green tea polyphenol extract attenuates ischemia/reperfusion injury of the gut.
AB  - Various studies have clearly demonstrated that green tea catechins possess potent
      antioxidative properties, and the preventive effects against various oxidative
      diseases have been reported. The aim of this study was to investigate the effect
      of green tea extract on the tissue injury caused by ischemia/reperfusion (I/R) of
      the gut. I/R injury of the intestine was caused by clamping both the superior
      mesenteric artery and the celiac trunk for 45 min followed by release of the
      clamp allowing reperfusion for 1 h or 4 h. This procedure results in splanchnic
      artery occlusion (SAO) shock. Rats subjected to SAO developed a significant fall
      in mean arterial blood pressure, and only 10% of the animals survived for the
      entire 4-h reperfusion period. Surviving animals were sacrificed for histological
      examination and biochemical studies. Rats subjected to SAO displayed a
      significant increase in tissue myeloperoxidase (MPO) activity and malondialdehyde
      (MDA) levels, significant increases in plasma tumor necrosis factor (TNF)-alpha
      levels and marked injury to the distal ileum. Increased immunoreactivity to
      nitrotyrosine was observed in the ileum of rats subjected to SAO. Staining of
      sections of the ileum obtained from SAO rats with anti-intercellular adhesion
      molecule (ICAM-1) antibody and with anti-P-selectin antibody resulted in diffuse
      staining. Administration of green tea extract (20 and 10 mg kg(-1) i.v.) 15 min
      prior to the onset of gut reperfusion significantly reduced in a dose-dependent
      manner the fall in mean arterial blood pressure, the mortality rate, infiltration
      of the reperfused intestine with polymorphonuclear neutrophils (MPO activity),
      lipid peroxidation (MDA levels), production of TNF-alpha, and histological
      evidence of gut injury. Administration of green tea extract also markedly reduced
      nitrotyrosine formation and the up-regulation of ICAM-1 and P-selectin during
      reperfusion. In order to clarify that green tea extract might be useful in the
      therapy of I/R injury, we also investigated the effect of green tea extract (20
      mg kg(-1) i.v.) when administered 5 min after the onset of gut reperfusion.
      Similar to the pretreatment approach, the post-treatment also significantly
      reduced the gut injury induced by I/R. These results demonstrate that green tea
      extract significantly reduces I/R injury of the intestine.

PMID- 15997393
TI  - Effect of carticaine on the sarcoplasmic reticulum Ca2+-adenosine triphosphatase.
      II. Cations dependence.
AB  - Ca2+-ATPase is a major intrinsic protein in the sarcoplasmic reticulum (SR) from
      skeletal muscles. It actively transports Ca2+ from the cytoplasm to the SR lumen,
      reducing cytoplasmic [Ca2+] to promote muscle relaxation. Carticaine is a local
      anesthetic widely used in operative dentistry. We previously showed that
      carticaine inhibits SR Ca2+-ATPase activity and the coupled Ca(2+) uptake by
      isolated SR vesicles, and increases the rate of Ca2+ efflux from preloaded
      vesicles. We also found that these effects were antagonized by divalent cations,
      and concluded that they were mainly due to the direct interaction of carticaine
      with the Ca2+-ATPase protein. Here we present additional results on the
      modulation of the above effects of carticaine by Ca2+ and Mg2+. The activating
      effect of Ca2+ on the ATPase activity is competitively inhibited by carticaine,
      indicating a decreased Ca2+ binding to the high affinity Ca2+ transport sites.
      The activating effect of Mg2+ on the phosphorylation of Ca2+-ATPase by
      orthophosphate is also inhibited by carticaine. The anesthetic does not affect
      the reaction mechanism of the cations acting as cofactors of ATP in the catalytic
      site. On the basis of the present and our previous results, we propose a model
      that describes the effect of carticaine on the Ca2+-ATPase cycle.

PMID- 15997394
TI  - Prior vasorelaxation enhances diadenosine polyphosphate-induced contractility of
      rat mesenteric resistance arteries.
AB  - Low-threshold concentrations of diadenosine polyphosphates (ApnA: Ap3A, Ap4A,
      Ap5A, Ap6A) or ATP, which at basal vessel tone induce just measurable
      vasoconstrictions, induce up to ten times enhanced vasoconstrictions of
      previously relaxed (by acetylcholine or sodium nitroprusside or 8Br2 cGMP or
      isoproterenol or levcromakalim) pre-contracted rat mesenteric resistance arteries
      (MrA) in a microvessel-myograph. These enhanced vasoconstrictions were of similar
      magnitude for threshold concentrations of all ApnA.Possibly, the low
      concentrations of ApnA reverse the prior vasorelaxation by inhibiting a common
      vasorelaxation pathway, but obviously this is not due to inhibition of guanylate
      cyclase, which has been previously described to be inhibited by ApnA, because the
      enhanced vasoconstrictions can be observed with guanylate cyclase-independent
      vasorelaxants (8Br2 cGMP, isoproterenol or levcromakalim), too. The enhanced
      vasoconstrictions are endothelium-independent because after mechanical vascular
      de-endothelialization the results were identical. De-endothelialized vessels,
      which fail to relax by acetylcholine, showed no enhanced ApnA-induced
      vasoconstrictions, demonstrating that the mere prior vasorelaxation of the vessel
      is required to provide the enhanced vasoconstriction by ApnA. Furthermore, the
      enhanced contractility is not based on a potentiation of the phenylephrine
      contraction because it equally occurs with other agents used for arterial pre
      contraction. Systemically applied ApnA considerably decrease arteriovascular
      resistance, resulting in hypotension. But here it is demonstrated that a
      preceding vasorelaxation enables the resistance arteries to generate a strong and
      persistent ApnA-induced vasoconstriction. Thus, in vivo at very low
      concentrations ApnA may serve to counteract severe conditions of hypotension
      (e.g., shock syndrome or anaphylaxis) by the constriction of resistance arteries.

PMID- 15997396
TI  - A new technique combining both polypropylene and vaginal wall sling procedures:
      can it minimize the risk of urethral and vaginal erosion occurring with synthetic
      materials?
AB  - We describe a new technique combining in situ vaginal wall and polypropylene mesh
      slings that may decrease potential erosive complications caused by synthetic
      materials. A folded mucosal patch harboring the polypropylene mesh was placed
      between mid-urethra and bladder neck. Using this technique, 12 consecutive women
      (age range 44-66 years) were operated. Preoperative evaluation included a
      detailed history, pelvic examination, stress test, cystourethroscopy, basic
      urodynamic evaluation (cystometry, Valsalva leak point pressure measurement), and
      urine culture. Based on these evaluations, three, seven, and two patients had
      type I, II, and III stress urinary incontinence, respectively. A paraurethral
      cyst excision was carried out in one patient and anterior colporrhaphy in four
      patients during the same operation. No ischemia or sloughing at the operation
      site occurred in any case. Pelvic examination was repeated in all patients after
      3 and 6 months of follow-up and symptoms were determined after 12 months of
      follow-up in eight patients by telephone interview. Average follow-up was 10
      months (range: 6-14 months). None of the patients were incontinent, or complained
      of sexual dysfunction or erosive complications after 1 year. Since there are two
      distinct barriers between the sling and both urethra and vagina, our technique
      covers all advantages of a sling procedure with synthetic materials and avoids
      the risk of urethral and vaginal erosion. The other advantage of this technique
      is the concomitant utilization of the vaginal wall as sling material.

PMID- 15997395
TI  - Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells
      and monocyte-derived dendritic cells.
AB  - Initial vaccine developments for renal cell carcinoma (RCC) have concentrated on
      cell-based approaches in which tumor cells themselves provide mixtures of unknown
      tumor-associated antigens as immunizing agents. Antigens derived from autologous
      tumors can direct responses to molecular composites characteristic of individual
      tumors, whereas antigens derived from allogeneic tumor cells must be commonly
      shared by RCC. Three types of cell-based vaccine for RCC have been investigated:
      isolated tumor cell suspensions, gene modified tumor cells and dendritic cells
      (DCs) expressing RCC-associated antigens. Approaches using genetic modification
      of autologous RCC have included ex vivo modification of tumor cells or
      modification of tumors in vivo. We have used gene-modification of allogeneic
      tumor cell lines to create generic RCC vaccines. More recently, emphasis has
      shifted to the use of DCs as cell-based vaccines for RCC. DCs have moved to a
      position of central interest because of their excellent stimulatory capacity,
      combined with their ability to process and present antigens to both naive CD4 and
      CD8 cells. The long impasse in identifying molecular targets for specific
      immunotherapy of RCC is now rapidly being overcome through the use of tools and
      information emerging from human genome research. Identification of candidate
      molecules expressed by RCC using cDNA arrays, combined with protein arrays and
      identification of peptides presented by MHC molecules, allow specific vaccines to
      be tailored to the antigenic profile of individual tumors, providing the basis
      for development of patient-specific vaccines.

PMID- 15997398
TI  - Amphiphile-induced tubular budding of the bilayer membrane.
AB  - Amphiphile-induced tubular budding of the erythrocyte membrane was studied using
      transmission electron microscopy. No chiral patterns of the intramembraneous
      particles were found, either on the cylindrical buds, or on the tubular
      nanoexovesicles. In agreement with these observations, the tubular budding may be
      explained by in-plane ordering of anisotropic membrane inclusions in the buds
      where the difference between the principal membrane curvatures is very large. In
      contrast to previously reported theories, no direct external mechanical force is
      needed to explain tubular budding of the bilayer membrane.

PMID- 15997397
TI  - Smoking-induced increase in urinary cadmium levels among Japanese women.
AB  - OBJECTIVE: To examine if cigarette smoking will induce elevation in cadmium (Cd)
      in urine. METHODS: Information on smoking habits, and urinary levels of cadmium
      (Cd-U), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG),
      creatinine (CR or cr), and urine specific gravity (SG or sg) was cited from a
      combination of three previously established databases on adult Japanese women.
      After exclusion of those with unclear answers on smoking habits (412 cases), the
      combination (12,846 cases) gave 11,092, 1420 and 334 cases of never, current and
      former smokers, respectively, for present statistical analyses. RESULTS: Multiple
      regression analyses taking Cd-U as a dependent variable and 11 regions of urine
      collection, age and smoking habits as independent variables showed that age and
      regions were powerful confounders in the analysis for the effects of smoking on
      Cd-U. To exclude the confounding effects, current and former smokers were paired
      with age- and region-matched never smoking controls in subsequent analyses. In
      addition, former smokers were paired with age- and region-matched current
      smokers. The comparison of the paired cases showed that Cd-U for current smokers
      was significantly higher than that for never smokers. The levels for former
      smokers were however not higher than the levels for never smokers. When
      classified by the number of cigarettes consumed per day, Cd-U for current smokers
      increased dependently to the number of cigarettes (about 0.09
      microg/cigarette/day) with leveling off at 15 or more cigarettes. There was a
      subtle cigarette dose-dependent increase in alpha(1)-MG, but the increase was
      insignificant in case of beta(2)-MG. Estimation of the amount of Cd absorbed due
      to cigarette smoking followed by comparison with the increase in Cd-U suggested
      that almost all Cd absorbed will be excreted into urine. CONCLUSIONS: Among
      currently smoking Japanese women, cadmium in urine increased in a manner
      dependent to the number of cigarettes consumed daily. Thus, smoking is a
      confounder of Cd-U evaluation even among the population with relatively high
      dietary Cd burden.

PMID- 15997399
TI  - The use of climatic parameters and indices in vegetation distribution. A case
      study in the Spanish Sistema Central.
AB  - In this study, over 100 phytoclimatic indices and other climatic parameters were
      calculated using the climatic data from 260 meteorological stations in a
      Mediterranean territory located in the centre of the Iberian Peninsula. The
      nature of these indices was very different; some of them expressed general
      climatic features (e.g. continentality), while others were formulated for
      different Mediterranean territories and included particular limits of those
      indices that expressed differences in vegetation distribution. We wanted to know
      whether all of these indices were able to explain changes in vegetation on a
      spatial scale, and whether their boundaries worked similarly to the original
      territory. As they were so numerous, we investigated whether any of them were
      redundant. To relate vegetation to climate parameters we preferred to use its
      hierarchical nature, in discrete units (characterized by one or more dominant or
      co-dominant species), although it is known to vary continuously. These units give
      clearer results in this kind of phytoclimatic study. We have therefore used the
      main communities that represent natural potential vegetation. Multivariate and
      estimative analyses were used as statistical methods. The classification showed
      different levels of correlation among climatic parameters, but all of them were
      over 0.5. One hundred and eleven parameters were grouped into five larger groups:
      temperature (T), annual pluviothermic indices (PTY), summer pluviothermic indices
      (SPT), winter potential evapotranspiration (WPET) and thermal continentality
      indices (K). The remaining parameters showed low correlations with these five
      groups; some of them revealed obvious spatial changes in vegetation, such as
      summer hydric parameters that were zero in most vegetation types but not in high
      mountain vegetation. Others showed no clear results. For example, the Kerner
      index, an index of thermal continentality, showed lower values than expected for
      certain particular types of vegetation. Parameters relating to the water balance
      turned out to be very discriminative for separating vegetation types according to
      the season or the month when water begins to be scarce. Thus, water availability
      in soils is a limiting factor for the development of vegetation in spring or
      autumn as well as in summer. As expected, precipitation and temperature
      discriminated the altitudinal levels of vegetation. Finally, these index limits
      only worked in the territories where they were formulated, or in nearby areas.

PMID- 15997400
TI  - Sequences of predictive eye movements form a fractional Brownian series-
      implications for self-organized criticality in the oculomotor system.
AB  - When human subjects are presented with a pair of visual targets that alternate
      periodically, they track the targets with rapid eye movements known as saccades.
      In previous work we demonstrated that at low pacing rates (<0.5 Hz), saccades
      have a latency of about 180 ms, and the latencies are uncorrelated from trial to
      trial. At high pacing rates (>0.6 Hz), latencies are much shorter: subjects make
      predictive saccades that anticipate target motion. The predictive latencies are
      correlated and appear to form a fractional Brownian motion. Here we confirm this
      finding by examining the rate of decay of nonlinear forecasting of predictive
      latencies. We further characterize the nature of predictive saccade latencies
      through the use of detrended fluctuation analysis and surrogate data. These
      results lead us to conclude that predictive saccades may exhibit a form of self
      organized criticality, which enables rapid response to changes in stimulus
      timing. We provide an experimental demonstration of this.

PMID- 15997401
TI  - [Distribution of pain parameters for chronic pain patients in comparison to the
      general population].
AB  - OBJECTIVE: The study analyzes pain complaints of chronic pain patients in
      comparison to representative data from the general population. METHODS: In a
      cross-sectional study 493 patients from different health care settings were
      interviewed about their pain during the previous 12-month and the currently
      strongest pain. Locations, frequency, intensity and duration of pain,
      restrictions in daily activities and utilization of therapies were assessed. For
      comparison data from the German federal health survey 1998 (n=6702) was used.
      RESULTS: The patients experienced pain more frequently and more severely than the
      general population. The largest difference was found in limitations of daily
      activities. Several qualitative similarities were observed, e.g. for the relative
      frequency of pain locations. Most patients reported multiple pain locations. The
      number of reported pain locations increased with intensity and duration of pain.
      Women reported more frequent and stronger pain than men, utilized more therapies
      and underwent more often alternative treatments. CONCLUSIONS: The high prevalence
      of pain complaints in both samples indicates the importance of early pain
      prevention, adequate diagnosis and treatment in order to obviate the development
      and chronification of pain.

PMID- 15997402
TI  - [Antibacterial photodynamic therapy. A new treatment for superficial bacterial
      infections?].
AB  - The basis of "antibacterial photodynamic therapy" involves the killing of
      bacteria by reactive oxygen species in the presence of a photosensitizer and
      light. Possible dermatologic indications include inactivation of bacteria in skin
      and wound infections and reduction in density of nosocomial multi-resistant
      infections. The chief advantage of antibacterial photodynamic therapy is that
      regardless of the resistance pattern of a bacteria, inactivation can be achieved,
      analogous to the use of antiseptics. The aim of the present review is to describe
      the physicochemical and biological mechanisms of antibacterial photodynamic
      therapy as well as possible clinical indications in dermatology.

PMID- 15997403
TI  - Impact of a microphallid trematode on the behaviour and survival of its isopod
      intermediate host: phylogenetic inheritance?
AB  - The extent to which the ability of parasites to alter host behaviour is
      phylogenetically inherited as opposed to independently evolved has received
      little attention. We investigated the impact of an undescribed species of
      Microphallus on the behaviour and survival of its host, the freshwater isopod
      Austridotea annectens, to determine if it produced effects comparable to those
      induced by other trematodes of this genus. There was no difference between the
      vertical distribution and responses to light of infected isopods and those of
      uninfected isopods. In contrast, we found that infected isopods were more active
      swimmers than uninfected isopods, and that they failed to show the evasive
      responses shown by uninfected isopods when exposed to a simulated predator. There
      was no detectable effect of Microphallus infection on isopod survival, however.
      Overall, our results provide no strong evidence that the behavioural manipulation
      shown by our Microphallus species and that displayed by the well-studied
      Microphallus papillorobustus are inherited from a common ancestor rather than
      independently derived.

PMID- 15997404
TI  - Penetration of the salivary glands of Rhodnius domesticus Neiva & Pinto, 1923
      (Hemiptera: Reduviidae) by Trypanosoma rangeli Tejera, 1920 (Protozoa:
      Kinetoplastida).
AB  - Penetration of the heteroxenous protozoan Trypanosoma rangeli into the salivary
      glands of its invertebrate host Rhodnius domesticus has been investigated here
      using different approaches. Electron microscopy showed that epimastigotes coming
      from the insect hemocoel cross the basal lamina that surrounds the salivary
      glands and penetrate through the gland cells cytoplasm. After reaching the gland
      lumen, epimastigote forms remain adhered to the gland cell microvilli by their
      flagella, while metacyclic trypomastigotes are found swimming free in the saliva.
      Analysis by flow cytometry, western blotting and hemolytic activity allowed to
      demonstrate the presence in T. rangeli of a hemolytic molecule with antigenic
      cross-reactivity with murine perforin, which could be used by the parasites to
      reach the salivary gland lumen. This molecule, which we named as rangelysin, has
      120 kDa molecular weight, is able to induce hemolysis only in acidic pH, and is
      produced by both trypomastigote and epimastigote forms.

PMID- 15997405
TI  - Cryptosporidium infection in livestock and first identification of
      Cryptosporidium parvum genotype in cattle feces in Taiwan.
AB  - Fecal survey by modified Ziehl-Neelsen (MZN) method and immunofluorescence assay
      (IFA) of Cryptosporidium infection in cattle and goats in Taiwan showed a
      prevalence of 37.6% (173/460) and 35.8% (44/123), respectively. In addition to
      the calves, adult cattle were also found to be shedding Cryptosporidium oocyst.
      No significant difference was observed between diarrheic and non-diarrheic cattle
      feces with regard to the presence of Cryptosporidium oocyst. Two groups of
      oocysts with different diameter sizes, possibly indicating two different species,
      were observed in the cattle feces. By PCR analysis using primers directed against
      the 18S rRNA gene, followed by sequencing of the amplicon, we were able to
      confirm that one of the oocyst species belong to that of the bovine genotype of
      Cryptosporidium parvum. This is the first identification of a genotype of C.
      parvum oocyst in the feces of cattle in Taiwan.

PMID- 15997406
TI  - What are the factors determining the probability of discovering a flea species
      (Siphonaptera)?
AB  - Our aim was to determine which of four variables (number of host species
      exploited by the parasite, taxonomic distinctness of these hosts, geographic
      range of the principal host, and year of description of this host) was the best
      predictor of description date of fleas. The study used previously published data
      on 297 flea species parasitic on 197 species of small mammals from 34 different
      regions of the Holarctic and one region from the Neotropics. We used both simple
      linear and multiple regressions to evaluate the relationships between the four
      predictor variables and the year of flea description, on species values as well
      as on phylogenetically independent contrasts. Whether or not the analyses
      controlled for flea phylogeny, all predictor variables correlated significantly
      with year of flea description when tested separately. In multiple regressions,
      however, the number of exploited host species was the best predictor of the date
      of flea description, with the geographic range of the principal host species as
      well as the date of its description having a lesser, though significant,
      influence. Overall, our results indicate that a flea species is more likely to be
      discovered and described early if its biological characteristics (exploitation of
      many host species) and those of its hosts (long-known to science, broad
      geographic distributions) increase its chances of being included in a collection.
      Because the variables we investigated only explained about 10-11% of the
      variation in year of description among flea species, other factors must be
      important, such as temporal variability in the activity of flea taxonomists.

PMID- 15997407
TI  - Effects of gamma radiation on Brugia malayi infective larvae and their
      intracellular Wolbachia bacteria.
AB  - Prior studies have shown that irradiated filarial larvae are developmentally
      stunted but capable of inducing partial immunity to filariasis in animals. The
      mechanisms for these effects are poorly understood. Recent studies suggest that
      intracellular Wolbachia bacteria are necessary for the normal development,
      reproduction and survival of filarial nematodes. The purpose of this study was to
      examine the effects of irradiation on Wolbachia in Brugia malayi infective larvae
      (L3) and on L3 development. The L3 were exposed to 0, 25, 35, 45, 55, 65 or 75
      krad of gamma irradiation from a (137) Cesium source and cultured in vitro at 37
      degrees C in NCTC/IMDM medium with 10% FCS for 12 days. Irradiation prevented
      molting of L3 to the L4 stage in a dose-dependent manner. Electron microscopy
      studies showed that irradiation damaged Wolbachia (25 krad) or cleared them from
      worm tissues (45 krad). In addition, majority of the irradiated L3s failed to
      develop the L4 cuticle. Real-time PCR studies showed that irradiation reduced
      Wolbachia DNA in worm tissues. Parallel in vivo studies confirmed decreased
      development of irradiated L3 in jirds, with associated effects on Wolbachia.
      Jirds injected s.c with normal L3 developed antibodies to Wolbachia surface
      protein (wsp) shortly after the onset of microfilarial patency. In contrast,
      jirds injected with irradiated L3 did not develop microfilaremia or antibodies to
      wsp. Additional studies are needed to test the hypothesis that irradiation
      retards growth and development of filarial L3 by killing Wolbachia.

PMID- 15997408
TI  - Relationship between heat shock protein levels and infectivity in Trichinella
      spiralis larvae exposed to different stressors.
AB  - The aim of the present study was to investigate the relationship between
      infectivity and the levels of two major heat shock proteins (Hsp70 and Hsp60) in
      Trichinella spiralis larvae. Parasites were exposed to either sublethal thermal
      stress (43 and 45 degrees C) or to warm or cold temperature oxidative stress. The
      stressed larvae were then inoculated into female CD1 mice to determine their
      infectivity. Hsps were detected and quantified by Western blotting using
      monoclonal antibodies. Infectivity was expressed as larvae per gram of muscle.
      Warm temperature oxidative stress (20 mM H2O2 at 37 degrees C) caused a
      significant increase in Hsp levels and total loss of infectivity. Cold oxidative
      stress (20 mM H2O2 at 4 degrees C) caused no alterations in either Hsp levels or
      infectivity. However, high oxidative stress and cold (200 mM H2O2 at 4 degrees C)
      caused a slight increase in Hsp60 levels and a drastic reduction in infectivity.
      Exposure of the larvae to 43 or 45 degrees C did not significantly alter Hsp
      levels or infectivity. These results show that (i) cold reduces the deleterious
      effects of oxidative stress; (ii) heat induces neither increased Hsp60/Hsp70
      levels nor reduces infectivity; (iii) increased Hsp levels induced by oxidative
      stress may cause lower infectivity.

PMID- 15997409
TI  - Detection of serum antibody to Entameba histolytica in various population samples
      of amebic infection using an enzyme-linked immunosorbent assay.
AB  - Microscopic identification of Entameba histolytica in stool is insensitive to
      differentiate this pathogenic ameba from morphologically identical Entameba
      dispar. An enzyme-linked immunosorbent assay method was applied for diagnosing
      amebiasis by detection of E. histolytica antibody. A total of 258 sample sera
      were analyzed from five different groups including amebiasis patients, E.
      histolytica/E. dispar asymptomatic cyst carriers, patients clinically presumed to
      have intestinal and extra-intestinal amebiasis and healthy control. From 51 E.
      histolytica/E. dispar cysts passers identified by microscopy and culture, a
      positive anti-amebic antibody was measured only for eight specimens (15.6%) and
      43 cyst carriers showed an absorbance less than cut-off likely due to E. dispar
      infection. These findings suggest usefulness of ELISA method in differentiation
      of Entameba species, in clinical laboratories less equipped with biological and
      biochemical methods or antigen capture kits.

PMID- 15997410
TI  - Lethal LPS-independent side effects after microfilaricidal treatment in
      Acanthocheilonema viteae-infected rodents.
AB  - Mastomys coucha and jirds infected with Acanthocheilonema viteae, a filarial
      species free of endosymbiontic bacteria of the genus Wolbachia, suffer lethal
      side effects after effective microfilaricidal therapy with diethylcarbamazine and
      levamisole, whereas, M. coucha infected with the Wolbachia-infested species
      Brugia malayi or Litomosoides carinii tolerate corresponding treatment. Mortality
      in A. viteae infected, treated animals varied with microfilariae density in the
      blood. It was up to 100% in highly microfilaraemic M. coucha and jirds, but low
      or absent in animals with low microfilariae counts. Deaths occurred in most cases
      5-24 h after treatment. Characteristic symptoms in animals, which died
      subsequently were a rapid drop in body temperature by 4-7 degrees C, an increase
      in hematokrit values by up to 10% and a moderate blood acidosis. Lethal effects
      in A. viteae infections did not depend on a particular status of hypersensitivity
      of the animals since desensitization procedures, which protected infected M.
      coucha against an otherwise lethal intravenous challenge with A. viteae
      homogenate did not protect against adverse reactions to a subsequent
      microfilaricidal treatment. The animals were protected from treatment induced
      death by injection of N-LMMA. Thus the final morbific agent seems NO. The data
      show that adverse effects after effective microfilaricidal therapy may be caused
      by microfilariae derived components different from Wolbachia-released LPS.

PMID- 15997411
TI  - Synthesis and biodistribution of an 18F-labelled resveratrol derivative for small
      animal positron emission tomography.
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a naturally occurring
      phytoalexin and polyphenol existing in grapes and various other plants, and one
      of the best known 'nutriceuticals'. It shows a multiplicity of beneficial
      biological effects, particularly, by attenuating atherogenic, inflammatory, and
      carcinogenic processes. However, despite convincing evidence from experimental
      and clinical studies, data concerning the role of resveratrol and other members
      of the large polyphenols family for human health is still a matter of debate. One
      reason for this is the lack of suitable sensitive and specific methods, which
      would allow direct assessment of biodistribution, biokinetics, and the metabolic
      fate of these compounds in vivo. The unique features of positron emission
      tomography (PET) as a non-invasive in vivo imaging methodology in combination
      with suitable PET radiotracers have great promise to assess quantitative
      information on physiological effects of polyphenols in vivo. Herein we describe
      the radiosynthesis of an (18)F-labelled resveratrol derivative, 3,5-dihydroxy-4'
      [(18)F]fluoro-trans-stilbene ([(18)F]-1), using the Horner-Wadsworth-Emmons
      reaction as a novel radiolabelling technique in PET radiochemistry for subsequent
      functional imaging of polyphenol metabolism in vivo. In a typical "three-step/one
      pot" reaction, (18)F-labelled resveratrol derivative [(18)F]-1 could be
      synthesized within 120-130 min including HPLC separation at a specific
      radioactivity of about 90 GBq/mumol. The radiochemical yield was about 9% (decay
      corrected) related to [(18)F]fluoride and the radiochemical purity exceeded 97%.
      First radiopharmacological evaluation included measurement of biodistribution ex
      vivo and positron emission tomography (PET) studies in vivo after intravenous
      application of [(18)F]-1 in male Wistar rats using a dedicated small animal PET
      camera with very high spatial resolution. Concordantly with data on
      bioavailability and metabolism of native resveratrol from the literature, these
      investigations revealed an extensive uptake and metabolism in the liver and
      kidney, respectively, of [(18)F]-1. This study represents the first investigation
      of polyphenols in vivo by means of PET.

PMID- 15997412
TI  - Aspects of positron emission tomography radiochemistry as relevant for food
      chemistry.
AB  - Positron emission tomography (PET) is a medical imaging technique using compounds
      labelled with short-lived positron emitting radioisotopes to obtain functional
      information of physiological, biochemical and pharmacological processes in vivo.
      The need to understand the potential link between the ingestion of individual
      dietary agents and the effect of health promotion or health risk requires the
      exact metabolic characterization of food ingredients in vivo. This exciting but
      rather new research field of PET would provide new insights and perspectives on
      food chemistry by assessing quantitative information on pharmocokinetics and
      pharmacodynamics of food ingredients and dietary agents. To fully exploit PET
      technology in food chemistry appropriately radiolabelled compounds as relevant
      for food sciences are needed. The most widely used short-lived positron emitters
      are (11)C (t(1/2) = 20.4 min) and (18)F (t(1/2) = 109.8 min). Longer-lived
      radioisotopes are available by using (76)Br (t(1/2) = 16.2 h) and (124)I (t(1/2)
      = 4.12 d). The present review article tries to discuss some aspects for the
      radiolabelling of food ingredients and dietary agents either by means of isotopic
      labelling with (11)C or via prosthetic group labelling approaches using the
      positron emitting halogens (18)F, (76)Br and (124)I.

PMID- 15997413
TI  - Protein-bound advanced glycation endproducts (AGEs) as bioactive amino acid
      derivatives in foods.
AB  - The Maillard reaction or nonenzymatic browning is of outstanding importance for
      the formation of flavour and colour of heated foods. Corresponding reactions,
      also referred to as "glycation", are known from biological systems, where the
      formation of advanced glycation endproducts (AGEs) shall play an important
      pathophysiological role in diabetes and uremia. In this review, pathways leading
      to the formation of individual protein-bound lysine and arginine derivatives in
      foods are described and nutritional consequences resulting from this
      posttranslational modifications of food proteins are discussed.

PMID- 15997414
TI  - Short-term cognition deficits during early alcohol withdrawal are associated with
      elevated plasma homocysteine levels in patients with alcoholism.
AB  - Higher plasma homocysteine levels have been found in actively drinking alcoholics
      as well as in early abstinent patients. Furthermore, elevated homocysteine levels
      are associated with cognitive decline in dementia and in healthy elderly people.
      The aim of this prospective study was to investigate a possible association
      between homocysteine serum levels and clinically well known cognitive deficits
      during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during
      early withdrawal treatment. Cognitive function was assessed using the c.I.-Test.
      Patients with cognitive deficits showed significantly higher homocysteine serum
      levels (Mann-Whitney-U, p=0.004) than patients without cognitive deficits, while
      the difference in blood alcohol concentration was not significant. Using logistic
      regression analysis, cognitive deficits were best predicted by high homocysteine
      serum levels (Wald chi2=4.071, OR=1.043, 95% CI 1.001-1.086, p<0.05), which was
      confirmed by Receiver Operating Curves (AUC=0.68, 95% CI=0.57-0.79, p=0.004). The
      present results show first evidence of an association between elevated plasma
      homocysteine levels in alcoholics and cognition deficits in patients undergoing
      alcohol withdrawal.

PMID- 15997415
TI  - How to diagnose MSA early: the role of magnetic resonance imaging.
AB  - The clinical differentiation between Parkinson's disease (PD) and multiple system
      atrophy (MSA) remains a challenge for each neurologist. The use of different
      magnetic resonance imaging (MRI) techniques including conventional MRI, proton
      magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI),
      magnetization transfer imaging (MTI) and MR volumetry (MRV) offer the potential
      for objective criteria in the differential diagnosis of neurodegenerative
      parkinsonism. The aim of this article is to review the role of different MRI
      techniques in the differential diagnosis of PD and MSA.

PMID- 15997416
TI  - Region specific distribution of levomepromazine in the human brain.
AB  - OBJECTIVE: The aim of this study was to examine concentrations of levomepromazine
      and its metabolite desmethyl-levomepromazine in different regions of human brain
      and in relationship to drug-free time. METHODS: Drug concentrations were measured
      in up to 43 regions of 5 postmortem human brains of patients previously treated
      with levomepromazine. To enable statistical comparison across brain regions
      several smaller brain areas were put together to form larger brain areas (cortex
      cerebri, limbic system, cerebellum, basal ganglia, thalamus). Mean values of drug
      concentrations in these larger brain areas were used in a repeated measurement
      ANOVA to analyze for region specific distribution. The elimination half-life in
      brain tissue was estimated with a NONMEM population kinetic analysis using the
      mean value of all brain regions of an individual case. RESULTS: Levomepromazine
      and desmethyl-levomepromazine appear to accumulate in human brain tissue relative
      to blood. Mean concentrations differed largely between individual brains, in part
      due to differences in dose of drug, duration of treatment and drug-free time
      before death. There was an apparent region-specific difference in levomepromazine
      concentrations with highest values in the basal ganglia (mean 316 ng/g) and
      lowest values in the cortex cerebri (mean 209 ng/g). The elimination half-life
      from brain tissue is longer than from blood and was calculated to be about one
      week. Similar results were obtained with desmethyl-levomepromazine. CONCLUSIONS:
      Levomepromazine shows a region-specific distribution in the human brain with
      highest values in the basal ganglia. This might be the consequence of low
      expression of the metabolic enzyme Cyp2D6 in the basal ganglia. If this finding
      is true also for other neuroleptic drugs it might increase our understanding of
      preferential toxicity of neuroleptic drugs against basal ganglia structures and
      higher volumes of basal ganglia of neuroleptic-treated patients. Furthermore,
      patients exposed to levomepromazine cannot be considered to be free of residual
      effects of the drug for a number of weeks after withdrawal.

PMID- 15997417
TI  - Association between body weight of newborn rats and density of serotonin
      transporters in the frontal cortex at adulthood.
AB  - Persisting alterations in monoaminergic innervation patterns have been observed
      following various environmental manipulations and neuro-psychopharmacological
      treatments during fetal or early postnatal life. The present study investigates
      the question how differences in initial growth conditions at birth might
      interfere with subsequent development of both serotonergic and noradrenergic
      innervation in the rat frontal cortex (FC) and brain stem. For this purpose,
      newborn rat littermates were divided into two groups, a low and a high birth
      weight group, and the densities of both serotonin (5-HT) and norepinephrine (NE)
      transporters in the FC and brain stem were analyzed at adulthood. 5-HT
      transporter density in the FC was significantly higher in the high birth weight
      group as compared with the low birth weight group. No significant differences
      were observed between both groups in the density of 5-HT transporters in the
      brain stem and in the densities of NE transporters in FC and brain stem. It is
      discussed that differences in birth weight may affect the postnatal development
      of 5-HT projections to the frontal cortex.

PMID- 15997419
TI  - The CSF levels of total-tau and phosphotau in patients with relapsing-remitting
      multiple sclerosis.
AB  - Total-tau protein is considered the marker of axon damage whereas the abnormally
      phosphorylated tau forms are mainly associated with Alzheimer's disease. An
      increase in total-tau levels was observed in neurodegenerative diseases,
      including multiple sclerosis (MS). In order to find out whether the
      phosphorylated tau forms occur in MS patients and to evaluate their clinical
      significance, the levels of total-tau (t-tau) and tau phosphorylated at Thr 181
      (p-tau) were determined in 60 MS patients (40 during relapse including 18 with
      the first relapse and 20 stable) and in 18 age-matched controls. The
      determinations were conducted in the cerebrospinal fluid (CSF) using the ELISA
      method. The levels of t-tau and p-tau were higher in MS patients than in
      controls; however, increased levels were not related to the clinical activity of
      the disease. In CSF of the patients with the first relapse the level of t-tau was
      significantly increased whilst the level of p-tau was not elevated.

PMID- 15997418
TI  - Analysis of the polymorphic prion protein gene codon 129 in idiopathic
      Parkinson's disease.
AB  - Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown
      aetiology. Histopathological similarities between IPD and Creutzfeldt-Jakob prion
      disease (CJD) have been suggested. Homozygosity at polymorphic prion protein gene
      codon 129 (PRNP129) is a risk factor for developing CJD. Therefore we
      investigated a putative genetic link between CJD and IPD by studying PRNP129
      genotype segregation in 81 patients with IPD. We did not ascertain a different
      PRNP129 genotype distribution in IPD patients compared to healthy Germans. We
      found a significant difference in PRNP129 genotype in dependence of the clinical
      predominance type of IPD. Patients with tremor-dominant IPD presented less
      frequent a methionine homozygosis at PRNP129 than hypokinetic-rigid IPD patients
      (30% versus 62.5%; p<0.033). In conclusion, genotype distribution at codon 129 is
      obviously not essential in determining IPD. But our results may provide first
      evidence of an association between certain PRNP129 polymorphisms and the clinical
      presentation of IPD.

PMID- 15997420
TI  - Effectiveness of alendronate and etidronate in the treatment of osteoporosis in
      men: a prospective observational study.
AB  - The prevalence of osteoporosis in men is higher than previously assumed;
      consequently, numerous therapies are being investigated to treat these patients.
      The Canadian Database of Osteoporosis and Osteopenia patients (CANDOO) was
      analyzed to examine changes in bone mineral density (BMD) in consecutively seen
      osteoporotic men administered alendronate, etidronate or no bone-active drugs
      (control) over 1 year. A total of 244 men attending six Canadian osteoporosis
      clinics were included in the study (42 alendronate, 102 etidronate and 100
      control). Multiple imputation was used to model missing data to provide a more
      robust statistical model. The imputed datasets (five) were analyzed using
      multivariable linear regression to determine differences between groups in the
      percent change of lumbar spine (LS) and femoral neck (FN) BMD from baseline to 1
      year. Differences in the percent change in BMD from baseline were most notable at
      the LS in favor of alendronate (4.3%; 95% CI: 2.1, 6.6 ) and etidronate (2.1%;
      95% CI: 0.3, 4.0) therapy when compared with controls. At the LS, alendronate
      therapy led to significantly greater (2.2%; 95% CI: 0.2, 4.2) gains in BMD as
      compared to etidronate therapy. Compared to controls, there were no significant
      differences in FN BMD with alendronate (2.1%; 95% CI: -0.4, 4.7) or etidronate
      therapy (0.9%; 95% CI: -1.1, 2.8), nor were there significant differences between
      bisphosphonate groups (1.3%; 95% CI: -1.1, 3.6, in favor of alendronate). While
      both alendronate and etidronate significantly increased LS BMD in osteoporotic
      men after 1 year in real-world settings, alendronate therapy resulted in
      significantly superior gains in LS BMD. The effect of these two bisphosphonates
      on fractures and FN BMD in osteoporotic men is likely positive, but requires
      further study.

PMID- 15997421
TI  - Genetic and environmental influences on bone mineral density in pre- and post
      menopausal women.
AB  - Genetic factors influencing acquisition of peak bone mass account for a
      substantial proportion of the variation in bone mineral density (BMD), although
      the extent to which genes also contribute to variation in bone loss is debatable.
      Few prospective studies of related individuals have been carried out to address
      this issue. To gain insights into the nature of the genetic factors contributing
      to variation in BMD, we studied 570 women from large Amish families. We evaluated
      and compared the genetic contributions to BMD in pre- and post-menopausal women,
      with the rationale that genetic variation in pre-menopausal women is due
      primarily to genetic determinants of peak bone mass, while genetic variation in
      post-menopausal women is due to the combined genetic effects of peak bone mass
      and bone loss. Bone mineral density was measured at one point in time at the hip
      and spine by dual energy X-ray absorptiometry (DXA). We used variance
      decomposition procedures to partition variation in BMD into genetic and
      environmental effects common to both groups and to pre- and post-menopausal women
      separately. Total variation in BMD was higher in post- compared to pre-menopausal
      women. Genes accounted for 58-88% of the total variation in BMD in pre-menopausal
      women compared to 37-54% of the total variation in post-menopausal women. In
      absolute terms, however, the genetic variance was approximately similar between
      the two groups because the environmental variance was 3 1/2- to 4-fold larger in
      the post-menopausal group. The genetic correlation in total hip BMD was 0.81
      between pre- and post-menopausal women and differed significantly from one,
      consistent with the presence of at least some non-overlapping genetic effects in
      the two groups for BMD at this site. Overall, these analyses suggest that many,
      but not all, of the genetic factors influencing variation in BMD are common to
      both pre- and post-menopausal women.

PMID- 15997422
TI  - Down-regulation of N-methyl D-aspartate receptor in rat-modeled disuse
      osteopenia.
AB  - Lack of mechanical stress may result in osteoporosis; however, the underlying
      mechanisms of disuse osteoporosis remain unclear. It has been indicated that
      mechanical loading causes extracellular glutamate accumulation in osteoblasts. We
      hypothesized that the glutamate receptor mediation on bone cells might also be
      involved in mechanically stimulated osteogenesis. In this study, we investigated
      the changes of bone formation and the expressions of osteogenic genes and N
      methyl D-aspartate (NMDA) receptors, the major glutamate receptors, in disused
      bones. Rat modeled disuse osteopenia in hind limbs was induced by a 3-week tail
      suspension in Sprague-Dawley rats. Bone mineral density and trabecular bone
      volume of distal femurs were measured to verify the osteopenia of disused bones.
      The mRNA expressions of cbfa1/Runx2, type I collagen, alkaline phosphatase (ALP)
      and osteocalcin (OC) in bones were measured as osteogenic markers. The influences
      of mechanical unloading on the expressions of NMDA receptors (NR1 and NR2D) in
      bones were also examined. The effects of NMDA mediation on osteogenesis were
      tested by a treatment of MK-801, a non-competitive NMDA receptor antagonist, in
      cultured osteoblasts and bone marrow stroma cells. Our result showed that mRNA
      expressions of cbfa1/Runx2, type I collagen, ALP and OC were significantly
      decreased in disused bones. The mRNA and protein expressions of NR1 and NR2D were
      significantly decreased in disused bones; furthermore, immunolocalization of both
      receptors showed decreases in osteoblasts, but not in osteoclasts. The results
      from the in vitro study showed that MK-801 inhibited mRNA expression of
      cbfa1/Runx2 in bone marrow stroma cells and also inhibited those of collagen type
      I, ALP and OC of osteoblasts in a dose-dependent manner. These results suggest
      that NMDA receptor mediation may play an important role in transmitting
      mechanical loading in bones, and decreases of the expressions of NMDA receptors
      in disused bones, especially in osteoblasts, may contribute to the decrease of
      osteogenesis.

PMID- 15997424
TI  - [Hand surgical problems in haemodialysis patients].

PMID- 15997423
TI  - Osteoporosis in HFE2 juvenile hemochromatosis. A case report and review of the
      literature.
AB  - Juvenile hemochromatosis (JH) is a severe form of hemochromatosis, which involves
      rapid iron overload and leads to organ damage, typically before the age of 30. We
      report a single case of a 25-year-old man suffering from juvenile
      hemochromatosis, with aggressive clinical manifestations, typically characterized
      by transaminasemia and progressive erectile dysfunction, due to hypogonadotropic
      hypogonadism. The clinical case appears interesting, as the patient also had
      secondary osteoporosis accompanied by increased bone resorption, which
      prevalently affected trabecular bone. Approximately 6 months after normalization
      of serum ferritin levels was achieved by frequent phlebotomies, he became
      eugonadal and bone mineral density of the lumbar spine increased. Our
      observations suggest that osteoporosis might occur in the state of JH even at a
      young age, mainly due to the deprivation of sex steroids and the direct tissue
      toxicity of iron.

PMID- 15997425
TI  - [Carpal tunnel syndrome in haemodialysis patients: analysis of clinical and
      electrophysiological findings in 268 patients (395 hands)].
AB  - PURPOSE/BACKGROUND: Along with arthropathies, carpal tunnel syndrome (CTS) may
      occur in patients on chronic haemodialysis, its incidence is correlating with the
      duration of the haemodialysis treatment. To evaluate clinical and
      electrophysiological findings, relation of the disease to the side of the
      arteriovenous shunt, gender ratio, and a concurrent tendovaginosis stenosans
      (TVS), 268 haemodialysis-patients with CTS or recurrent CTS were retrospectively
      analyzed. METHODS AND (CLINICAL) MATERIAL: Over a period of ten years (1994 -
      2003), 268 haemodialysis patients presented to our peripheral neurosurgery
      practice with CTS or recurrent CTS. Diagnosis was confirmed with clinical and
      electrophysiological findings. The patients were divided into three groups based
      on their severity of disease as follows: Patients with only intermittent
      paraesthesias (CTS I degrees ), with persistent numbness in the area supplied by
      the median nerve (CTS II degrees ), and with paresis of the thenar muscles (CTS
      III degrees ). The average distal motor latency (DML), loss of sensory nerve
      action potentials (SNAP), and/or motor action potentials (MAP) were used as
      electrophysiological parameters. RESULTS: During the above mentioned period, 395
      primary CTS-operations were performed in 268 patients, and 83 operations of
      recurrent CTS in 53 patients, i.e. approximately 50 % of the patients had
      bilateral operations. A second recurrency of CTS was treated in 29 hands of 20
      patients and a third recurrency in six hands of five patients. The ratio of women
      to men suffering from CTS was approximately 1 : 1. TVS occurred concurrent in 22
      % of the patients in one hand and in 11.6 % in both hands. Decompression of the
      median nerve was performed more frequently on the shunt-side, or primarily on the
      shunt-side, if both hands were affected, as compared to the contralateral side.
      Recurrency of CTS, possibly a second or third recurrency, was found with
      increasing time of dialysis. The temporal interval from one operation to the
      other had a declining tendency. Whereas at the time of the primary operation in
      27.4 % of the patients a CTS I degrees was found, patients suffered from CTS II
      degrees or III degrees in case of a second or third recurrency. Deterioration of
      clinical signs in CTS recurrency was reflected by the electrophysiological
      findings with an increasing loss of SNAP and MAP. CONCLUSION: CTS is a typical
      complication of chronic haemodialysis, and differs from idiopathic CTS by a
      gender ratio of 1 : 1, a high frequency of concurrent TVS, as well as a tendency
      to recur. Since compression of the median nerve was found preferentially on the
      shunt-side, haemodynamic factors may play a role in the pathogenesis of the
      disease in addition to amyloidosis. Haemodialysis patients complaining of
      paraesthesia in their hands should undergo electrophysiological examination, even
      if a successful CTS-operation was performed in the past.

PMID- 15997426
TI  - [Recurrences of carpal tunnel syndrome in long-term haemodialysis patients].
AB  - BACKGROUND: Multiple recurrences of carpal tunnel syndrome and increased
      malfunction of the hand caused by tendopathies and arthropathies occur in long
      term (20 - 30 years) haemodialysis and are mainly influenced by beta2
      microglobulin amyloidosis. METHOD AND CLINICAL MATERIAL: 18 patients undergoing
      haemodialysis for an average of 29 years had been operated on 96 times for
      bilateral CTS and recurrent CTS during a mean observation period of 12.6 years.
      In nine patients (12 hands), removal of the thickened flexor digitorum
      superficialis tendons III and IV had been performed. All but two patients
      suffered from amyloidosis, 17 of them suffered from additional tendo- and 13 from
      additional arthropathies. All procedures were performed under local anaesthesia,
      and in half of them a tourniquet was used. The outcome was evaluated both
      clinically and with nerve conduction studies. RESULTS: 77 procedures for CTS
      recurrences were performed. The first recurrence was observed after an average of
      6.1 years (SD 2.8), the second after 4.6 (SD 3.1) and the third after 3.8 (SD
      1.9) years. Whereas in case of a first (occasionally second or extremely seldom
      in a third) recurrence, another re-opening of the carpal tunnel with or without
      synovectomy, was sufficient to improve symptoms in the majority of patients, this
      was occasionally the case with a second but rarely with the third recurrence. In
      these latter patients, only resection of thickened superficial flexor tendon
      bundles, showing marked amyloid-deposits histologically, resulted in improvement
      of pain, as well as finger mobility in one third of the patients. The distal
      motor latency of the median nerve recovered after the primary operation in 86 %,
      and after the second (first recurrence) only in 53 %. After the third operation
      (second recurrence), the results after tendon removal were better than in cases
      after synovectomy alone. CONCLUSION: In long-term (more than 20 - 30 years)
      haemodialysis patients suffering from arthropathies, tendopathies and recurrent
      carpal tunnel syndrome, removal of the flexor digitorum superficial tendons
      should be considered for the second recurrence to improve pain and finger
      mobility.

PMID- 15997427
TI  - [Angiological and neurological problems after shunt surgery in haemodialysis
      patients].
AB  - Vascular access induced complications contribute to the morbidity of patients on
      regular dialysis treatment. Impaired peripheral perfusion, cardiac stress and
      nerve lesions are the most common of these complications. In the first part of
      this paper, angiological problems caused by creating arterio-venous shunts are
      described. Shunt volumes, blood circulation in the shunt arm and shunt-induced
      alterations of the circulatory blood volume are discussed as well as the
      conditions under which these parameters gain pathogenic importance. After
      describing the different shunt-specific circulatory disturbances in detail, the
      whole spectrum of preventive interventions are discussed. Based on the author's
      experience during more than four decades in this field, it is strongly
      recommended to treat even slight but clinically relevant circulatory disorders
      caused by arterio-venous shunts. The second part of this paper deals with
      neurological complications in access surgery for dialysis. The pathogenesis of
      these complications and the measures necessary to avoid them are discussed.
      Depending on the skin incision, 5 to 20 % of the patients with fistulas between
      the radial artery and the cephalic vein at the wrist show lesions of the
      superficial branch of the radial nerve or of the lateral forearm nerve branches.
      Fistulas with the ulnar artery at the dorsal aspect of the lower forearm
      frequently cause irritations of the ulnar nerve's superficial palmar branch.
      Fistulas with the basilic vein in the upper arm often are associated with lesions
      of the medial cutaneous nerve of the forearm, especially when the vein is
      "subcuticularized". Aside from these rather benign lesions, sometimes severe
      sensomotoric functional losses of the median, radial, and ulnar nerves occur,
      predominantly after implantation of vascular graft shunts in the upper arm.
      Similar nerve damage can also be observed in association with severe impairment
      of the peripheral perfusion caused by this type of shunt. Nerve lesions resulting
      from severe ischemia are rather rare and most often develop in risk patients with
      preexisting poor peripheral perfusion.

PMID- 15997428
TI  - [Bilateral carpal tunnel syndrome with familial accumulation].
AB  - We report on a six-year-old girl with bilateral carpal tunnel syndrome with
      familial accumulation. Parents and one grandmother had positive history for CTS,
      treated by surgical decompression. Following neurologic and radiologic evaluation
      and after failed conservative treatment in a plaster cast, open carpal tunnel
      release was performed in a two-stage procedure. Postoperatively symptoms
      diminished and now six months after surgery, all complaints disappeared
      completely.

PMID- 15997429
TI  - [Soft-tissue coverage of the hand using the posterior interosseous artery flap].
AB  - Significant trauma, severe bacterial infections and tumour resections of the hand
      are often complicated by primary or secondary soft-tissue defects. The Posterior
      Interosseous Artery Flap (PIA), described by Zancolli and Angrigiani in 1985
      offers one possibility for soft-tissue coverage. In this abstract, we present the
      results of 35 patients who were treated with distally based PIA flap
      reconstructions during the years 1998 to 2003. 24 patients were available for one
      year follow-up and beyond. RESULTS: Long-term follow-up demonstrates excellent
      colour and texture match with reliable soft-tissue coverage. Two of the 33 flaps
      were lost because of ischemic necrosis. The incidence of distal local ischemia
      was predictable when the flaps were extended to the level of the PIP joint or
      beyond. CONCLUSION: The PIA flap affords a very durable and aesthetic option for
      soft-tissue coverage of the dorsum of the hand. The flap donor site can usually
      be closed primarily with little to no morbidity. In comparison to other local and
      distally based flaps such as the radial forearm flap, major blood vessels are
      spared. In summary, the PIA flap should be considered as a reliable and judicious
      alternative to free microvascular transfer procedures for soft-tissue defects of
      the hand proximal to the level of the PIP joint.

PMID- 15997430
TI  - [Defect coverage of the hand with the free serratus fascial flap].
AB  - PURPOSE: Coverage of exposed functional structures such as tendons, bones,
      vessels or nerves at the dorsal and palmar surface of the hand requires thin,
      supple tissue to provide adequate range of motion and a satisfying aesthetic
      result. Free fascial flaps are possible alternatives to cutaneous,
      fasciocutaneous and muscle flaps. The purpose of this retrospective study was to
      evaluate the functional and aesthetic results after coverage of the hand with
      free serratus fascial flaps in our department. METHOD AND CLINICAL MATERIAL: From
      1994 to 2002, ten patients underwent free fascial flap coverage of the hand with
      eleven serratus fascial flaps. Six patients could be re-examined and answered a
      questionnaire about their satisfaction with the functional and aesthetic results.
      The mean follow-up was after 34 months. RESULTS: Average active range of motion
      of the hand, functional improvement and the aesthetic result were satisfying in
      all follow-up patients. No secondary debulking or other contouring procedures
      were required. CONCLUSION: We recommend the use of free serratus fascial flaps as
      a valuable alternative to fasciocutaneous or muscle flaps since the functional
      results are excellent; no additional procedures were necessary and the
      aesthetical results are appealing.

PMID- 15997431
TI  - [Plasma concentration of endothelin-1 after myocutaneous latissimus dorsi
      transplantation -- role in reperfusion injury].
AB  - The success of a free flap transplantation is based on a sufficient
      microanastomosis which meets the following requirements: a pedicle placed without
      kinking or twisting, a good drainage, a well defined recipient vessel and
      integrity of the endothelium. The aim of this study was to determine whether
      operation-related ischaemia through flap transplantation and tourniquet induces
      an increase of Endothelin-1 plasma levels as one cause of vasospasm during
      microvascular procedures. We focused our attention in particular on the
      reperfusion period which is often limited to an irreversible perfusion failure of
      microcirculation due to free radicals, interleukin and Endothelin-1. Twenty-one
      patients with tissue injury of the lower leg were included in our study, fourteen
      underwent a latissimus dorsi muscle transplantation with a combined ischaemia,
      seven patients had a tourniquet ischaemia for tumour resection, debridement and
      local flap transfer. The duration of ischaemia varied due to the course of
      operation. The withdrawal of venous blood via central vein catheter, flap vein
      and wound bed followed a fixed time table pre- and post-reperfusion (T1:
      preoperative day via cubital vein, T2: 6th postoperative day, T3: 5 min, T4: 10
      min, T5: 15 min, T6: 1 h post-declamping and after tourniquet ischaemia via
      central vein catheter and T7: within 5 min from the flap vein immediate after
      recharging the flap). The vessel anastomosis determined the withdrawal from the
      local wound bed. ET-1 in venous blood samples were measured with ELISA. The
      duration of ischaemia in the tourniquet group ranged from 22 min up to 210 min
      with a mean of 76.58 min and in the latissimus group from 87 min up to 203 min
      with a mean of 139.21 min. The mean ET-1 plasma concentration measured
      systemically before operation in the 21 patients was 0.51 +/- 0.08 pg/ml (Mean +/
      SD). This result corresponds with data published in literature. The locally
      measured plasma levels of ET-1 after tourniquet and flap ischaemia were increased
      with 0.34 up to 3.90 pg/ml (0.95 +/- 0.79 pg/ml [Mean +/- SD]) for the tourniquet
      group and with 0.34 up to 14.87 pg/ml (1.85 +/- 3.64 pg/ml [Mean +/- SD]) for the
      latissimus group. This is an increase compared to systemically measured values as
      0.75 +/- 0.06 pg/ml (Mean +/- SD) for the tourniquet group and 0.58 +/- 0.21
      pg/ml (Mean +/- SD) for the latissimus group. We conclude that Endothelin-1 is
      increased locally in the early reperfusion period after free latissimus dorsi
      transplantation.

PMID- 15997432
TI  - [Improved fixation of finger prostheses by means of intramedullary titanium
      anchors and magnets].
AB  - BACKGROUND: A small series of patients with traumatic amputation of fingers have
      undergone treatment with a new technique using endomedullar osseointegrated
      titanium implant device that magnetically holds the finger prosthesis. METHODS: A
      two-stage reconstruction procedure with endomedullar osseointegrated titanium
      implants was performed to attach a finger prosthesis to the proximal, middle and
      distal phalanx. The first stage included implantation of the titanium fixture
      into the medullary cavity canal of the phalanx. After a 2-month rest period to
      allow the fixture to firmly osseointegrate with the phalanx of the bone, a skin
      penetrating titan-magnetic abutment was placed on top of the fixture, to which
      the prosthesis was firmly attached. RESULTS: Good stability could be achieved
      using an endomedullar osseointegrated prosthesis. Easy handling is possible with
      the magnetic connection between finger and prosthesis. In the clinical use were
      no complications observed. We observed no infections and no problems with the
      soft tissue. CONCLUSIONS: The combination of osseointegrated titanium implants
      and magnetics for finger prosthetics provides several advantages. Such as stable
      fixation of the prosthetic finger to the bone, restoration of some sensory
      feedback with better osseoperception as well as an excellent cosmetic result.

PMID- 15997433
TI  - [Verification of thumb-specific muscles in a triphalangeal thumb with magnetic
      resonance imaging].
AB  - The presence of three phalanges in the first digit is considered to be a
      relatively rare congenital hand malformation. Six groups of this deformity can be
      distinguished: some digits are opposable, others resemble a non-opposable five
      fingered hand. In cases of a hypoplastic thenar region with a restrained
      opposition, a clear verification of thumb-specific musculature has been hardly
      possible. We report of the possibility of a non-invasive identification of thumb
      specific muscles by means of magnetic resonance imaging.

PMID- 15997434
TI  - Silica-gel-confined ionic liquids: a new attempt for the development of supported
      nanoliquid catalysis.
AB  - A new concept of designing and synthesizing highly dispersed ionic-liquid
      catalysts was developed through physical confinement or encapsulation of ionic
      liquids (with or without metal complex) in a silica-gel matrix through a sol-gel
      process. We studied ionic liquids such as EMImBF4, BuMImBF4, DMImBF4, CMImBF4,
      BuMImPF6, either with or without [Pd(PPh3)2Cl2] and [Rh(PPh3)3Cl], in a silica
      gel matrix (E = ethyl, Bu = butyl M = methyl, D = decyl, C = cetyl and Im =
      imidazolium). The contents of ionic liquids and loadings of Pd or Rh were 8-53 wt
      % and 0.1 approximately 0.15 wt %, respectively. Analyses of FT-Raman spectra
      showed that abnormal Raman spectra of the confined ionic liquids were observed in
      comparison with the bulk and pure ionic liquids. EMImBF4 and BuMImBF4 ionic
      liquids could be completely washed out from the silica-gel matrix under vigorous
      reflux conditions, but ionic liquids with larger molecular size, for example,
      DMImBF4 or CMImBF4, could be confined into the silica-gel nanopores relatively
      firmly. These results suggested that the ionic liquids were physically confined
      or encapsulated into the silica gel. The N2 adsorption measurements indicated
      that the silica-gel skeleton was mesoporous with 50-110 A pore size after the
      BuMImBF4 ionic liquid was removed completely. Transmission electron microscopy
      (TEM) and X-ray diffraction (XRD) analysis showed that the silica-gel matrix was
      amorphous and non-uniformly mesoporous. Carbonylation of aniline and nitrobenzene
      for synthesis of diphenyl urea, carbonylation of aniline for synthesis of
      carbamates, and oxime transformation between cyclohexanone oxime and acetone were
      used as test reactions for these catalysts. Catalytic activities were remarkably
      enhanced with much lower amounts of ionic liquids needed with respect to bulk
      ionic-liquid catalysts or silica-supported ionic-liquid catalysts prepared with
      simple impregnation, in which the ionic liquid may be deposited as a thin layer
      on the support. Such unusual enhancement in catalytic activities may be
      attributed to the formation of nanoscale and high-concentration ionic liquids due
      to the confinement of the ionic liquid in silica gel; this results in unusual
      changes in the symmetry and coordination geometry of the ionic liquids.

PMID- 15997435
TI  - Rotamer stability in cis-[Pt(diA)G2] complexes (diA = diamine derivative and G =
      guanine derivative) mediated by carrier-ligand amine stereochemistry as revealed
      by circular dichroism spectroscopy.
AB  - Extensive investigations of cis-[Pt(diA)G2] complexes (in which G = a guanine
      ligand; diA = a single diamine ligand) revealed the types of interactions between
      the two G ligands and between the G and the cis-amine substituents when diA is a
      diamine ligand with substituents on each nitrogen atom being a small hydrogen
      atom and a bulky group able to slow the rotation about the Pt-G bond. All these
      interactions are shown to apply also when diA = dach (1,2-diaminocyclohexane),
      even though this chiral primary diamine has only small N-H atoms on each side of
      the coordination plane. However, a slight difference in the stereochemistry of
      the two protons (one N-H has "quasi axial" and the other "quasi equatorial"
      character) is sufficient to induce a significant change in the relative
      stabilities of the [Pt(dach)G2] deltaHT and lambdaHT rotamers (HT = head-to
      tail). The new results show that at acidic and neutral pH the induction of
      asymmetry from the dach ligand to the HT rotamers is governed by the G-to-G
      dipole-dipole interaction, which is greater for the six-membered ring of each
      guanine leaning towards the cis-G. Such a "six-in" canting of the two guanine
      ligands can be hampered by the steric interaction between the H8 of each guanine
      and the substituent on the cis-amine that is on the same side of the coordination
      plane. Such a repulsion is greater for a "quasi equatorial" N-H than for a "quasi
      axial" N-H. Under basic pH conditions, deprotonation of the guanine N1-H renders
      the O6 atom a much better hydrogen-bond acceptor; therefore, the stability of the
      HT rotamers is governed by the hydrogen-bond interaction of guanine O6 and the
      cis-amine N-H group. Such a guanine O6/N-H cis-amine interaction is stronger for
      a "quasi axial" than for a "quasi equatorial" N-H group. In the head-to-head (HH)
      rotamer, in which the electrostatic repulsion between electron-rich O6 atoms,
      both on the same side of the platinum coordination plane, tends to place the six
      membered rings of each guanine further from the cis-guanine and closer to the cis
      amine, we can expect better N-H...O6 hydrogen bonding for the "quasi equatorial"
      N-H groups.

PMID- 15997436
TI  - Influence of HMPA on the stereochemical outcome of the addition of a racemic
      allenylzinc onto enantiopure N-tert-butanesulfinimines: stereoselective access to
      enantiopure cis-ethynylaziridines.
AB  - In the presence of 60 equivalents of HMPA, the condensation of the racemic
      allenylzinc derived from 1-chloro-3-trimethylsilylpropyne onto enantiopure non
      alpha-branched N-tert-butanesulfinimines was proven to give access to the
      corresponding cis-ethynylaziridines as the major products. The good cis
      selectivity observed presumably resulted from a high kinetic resolution with the
      allenylzinc being partially configurationally labile with respect to the time
      scale defined by the rate of the reaction. Both single crystal X-ray analysis and
      semiempirical calculations conducted at the MM2 and AM1 levels of theory proved
      that the reaction certainly occurred through a preferred synclinal transition
      state in a supra- or antarafacial S(E)2' process. In all cases, chromatographic
      purification over silica gel allowed the cis-ethynyl-N-tert
      butanesulfinylaziridines to be obtained as diastereo- and enantiomerically pure
      compounds (dr >98:2 and ee >99%).

PMID- 15997437
TI  - Poly(lactide) stereocomplexes: formation, structure, properties, degradation, and
      applications.
AB  - Poly(lactide)s [i.e. poly(lactic acid) (PLA)] and lactide copolymers are
      biodegradable, compostable, producible from renewable resources, and nontoxic to
      the human body and the environment. They have been used as biomedical materials
      for tissue regeneration, matrices for drug delivery systems, and alternatives for
      commercial polymeric materials to reduce the impact on the environment. Since
      stereocomplexation or stereocomplex formation between enantiomeric PLA, poly(L
      lactide) [i.e. poly(L-lactic acid) (PLLA)] and poly(D-lactide) [i.e. poly(D
      lactic acid) (PDLA)] was reported in 1987, numerous studies have been carried out
      with respect to the formation, structure, properties, degradation, and
      applications of the PLA stereocomplexes. Stereocomplexation enhances the
      mechanical properties, the thermal-resistance, and the hydrolysis-resistance of
      PLA-based materials. These improvements arise from a peculiarly strong
      interaction between L-lactyl unit sequences and D-lactyl unit sequences, and
      stereocomplexation opens a new way for the preparation of biomaterials such as
      hydrogels and particles for drug delivery systems. It was revealed that the
      crucial parameters affecting stereocomplexation are the mixing ratio and the
      molecular weight of L-lactyl and D-lactyl unit sequences. On the other hand, PDLA
      was found to form a stereocomplex with L-configured polypeptides in 2001. This
      kind of stereocomplexation is called "hetero-stereocomplexation" and
      differentiated from "homo-stereocomplexation" between L-lactyl and D-lactyl unit
      sequences. This paper reviews the methods for tracing PLA stereocomplexation, the
      methods for inducing PLA stereocompelxation, the parameters affecting PLA
      stereocomplexation, and the structure, properties, degradation, and applications
      of a variety of stereocomplexed PLA materials.

PMID- 15997438
TI  - First aldehyde-functionalized poly(2-oxazoline)s for chemoselective ligation.
AB  - A protected aldehyde-functionalized 2-oxazoline, 2-[3-(1,3)-dioxolan-2-ylpropyl]
      2-oxazoline (DPOx), was synthesized from commercially available compounds in high
      yields. The polymerization of DPOx with different initiators proceeds via a
      living ionic mechanism; thus, the polymers were of low polydispersity and the
      degree of polymerization could be precisely adjusted. Copolymerization with 2
      methyl-2-oxazoline gave water-soluble statistical copolymers. Hydrolysis of the
      homo- and copolymers resulted in well-defined, aldehyde-bearing poly(2
      oxazoline)s. The aldehyde side functions reacted quantitatively with an amino-oxy
      compound to form the corresponding oxime.

PMID- 15997439
TI  - In situ-gelling, erodible N-isopropylacrylamide copolymers.
AB  - Copolymers of N-isopropylacrylamide, 2-hydroxyethyl methacryl lactate [(HEMA)
      lactate] and acrylic acid (AAc) were prepared with varying mole ratios of
      monomers to develop copolymers with gelation properties above a certain
      concentration for a bioerodible, in-situ gelling material. The copolymers formed
      gels in situ under physiological condition. The gelation temperature of the
      copolymers decreased as the HEMA-lactate content of the copolymers increased due
      to the hydrophobicity of HEMA-lactate, and increased as the AAc content increased
      due to the hydrophilicity of AAc. The gels redissolve at 37 degrees C as their
      LCSTs increase above 37 degrees C due to the hydrolysis of the HEMA-lactate
      pendant groups.

PMID- 15997440
TI  - Adverse effects of radiofrequency ablation of liver tumours in the Netherlands.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a new treatment for liver tumours.
      Complications encountered after RFA in the Netherlands were evaluated in the
      present study. METHODS: Between June 1999 and November 2003 patients undergoing
      RFA of irresectable liver tumours in eight medical centres were registered
      prospectively. RESULTS: One hundred and forty-three RFA procedures were performed
      in 122 patients. RFA was combined with partial hepatectomy in 37 instances. Death
      occurred after two procedures (1.4 per cent), and was mainly due to concomitant
      partial hepatectomy. A total of 19 major complications occurred after ten
      procedures, including biliary tract damage (seven patients), liver failure
      (four), hepatic abscess (three), peritoneal infection (two), intrahepatic
      haematoma (one), hepatic artery aneurysm (one) and pulmonary embolism (one).
      Twenty-four minor complications were related to concomitant partial hepatectomy
      or laparotomy. The overall complication rate was 20.3 per cent and the rate of
      complications related directly to RFA was 9.8 per cent. CONCLUSION: The procedure
      specific complication rate was almost 10 per cent and it is recommended that RFA
      should be performed only by an experienced team comprising a hepatobiliary
      surgeon, gastroenterologist, hepatologist and interventional radiologist. Biliary
      stricture, hepatic vascular damage and hepatic abscesses were the most common
      major complications.

PMID- 15997441
TI  - Surgery for clinical T3 carcinomas of the upper thoracic oesophagus and the need
      for new strategies.
AB  - BACKGROUND: Patients with T3 carcinomas have a dismal prognosis, even after
      complete resection of the primary tumour and metastatic nodes. This study focused
      on the clinicopathological characteristics and outcomes after surgical resection
      of clinical T3 carcinomas of the upper thoracic oesophagus. METHODS: Between
      January 1988 and February 2000, 888 consecutive patients underwent surgical
      removal of carcinomas of the thoracic oesophagus or oesophagogastric junction at
      the National Cancer Centre Hospital, Japan. The case records of 51 consecutive
      patients with clinical T3 tumours of the upper thoracic oesophagus were analysed
      retrospectively. RESULTS: No patient received preoperative therapy. Complications
      occurred in 41 (80 per cent). In-hospital and 30-day postoperative mortality
      rates were 10 and 4 per cent respectively. Gross residual primary tumour or
      metastasis in regional nodes invading adjacent structures was noted in 14
      patients (27 per cent) and incomplete resection including microscopic residual
      tumour in 23 (45 per cent). Overall 3- and 5-year survival rates were 20 and 12
      per cent; median survival was 13.1 months. CONCLUSION: Surgical resection of
      clinical T3 carcinomas of the upper thoracic oesophagus is associated with a high
      postoperative complication rate, incomplete resection and unsatisfactory outcome.
      Reconsideration of the surgical treatment strategy for these tumours is needed.

PMID- 15997442
TI  - Mapping changes in surgical mortality over 9 years by peer review audit.
AB  - BACKGROUND: There is increasing public scrutiny of deaths among surgical
      patients. This analysis sought evidence of changes in practice over time in the
      management of patients who died under surgical care. METHODS: The surgeons and
      anaesthetists in National Health Service hospitals providing the care of all
      surgical patients in Scotland participated in the Scottish Audit of Surgical
      Mortality (SASM). Data from peer review audit, critical event analysis and
      individual feedback of deaths while in surgical care over 9 years (1994-2002)
      were examined for trends over time. RESULTS: Over a 9-year period, 40,448
      patients died while in surgical care. Consultant surgeon and anaesthetist
      involvement in decision making and operating increased significantly (P < 0.001),
      and death after elective surgery declined to 0.27 per cent of elective
      operations. Adverse events were more frequently due to failures of hospital
      systems or process than to individual clinician errors. Fewer adverse events were
      identified as having contributed to or caused the death of patients over time (P
      < 0.001). Failure to use deep vein thrombosis (DVT) prophylaxis and failure to
      use high-dependency or intensive therapy units (HDU/ITU) became less common, once
      highlighted by the SASM. CONCLUSION: Through continuous peer review audit, the
      SASM has mapped and may have contributed to changes in surgical and anaesthetic
      practice over a 9-year period, indicating that the rate of adverse events can be
      decreased by changing clinician practice (DVT prophylaxis) and provision of
      facilities (HDU/ITU). Similar approaches should be considered by other medical
      specialties.

PMID- 15997443
TI  - Prevalence of family history of colorectal cancer in the general population.
AB  - BACKGROUND: Robust estimates of the prevalence of a family history of colorectal
      cancer in the general population are essential to inform planning of provision
      for colonoscopic surveillance and for clinical genetics services. However, there
      is a paucity of high-quality data. METHODS: Computerized record linkage was used
      to assess systematically the family history of 160 cancer-free community subjects
      and thereby provide prevalence data that are independent of participant recall.
      The data set comprised 2664 first- and second-degree relatives of study subjects,
      with 148 068 years at risk. RESULTS: Of people in the 30-70 years age range, 9.4
      (95 per cent confidence interval (c.i.) 5.8 to 14.9) per cent had a first-degree
      relative affected by colorectal cancer, and 28.8 (95 per cent c.i. 22.3 to 36.2)
      per cent had an affected first- or second-degree relative. Between 0 and 3.1 per
      cent of study subjects merited colonic surveillance, depending on the stringency
      of the guidelines used. CONCLUSION: An appreciable proportion of the general
      population has a relative affected by colorectal cancer, sufficient to merit
      screening under certain criteria. In the absence of good-quality evidence
      supporting colonoscopic surveillance in groups at moderate risk, these data
      directly inform the planning of services for people with a family history of
      colorectal cancer. However, the clinical risk and financial implications of
      screening should be taken into account.

PMID- 15997444
TI  - Biopsy of resectable colorectal liver metastases causes tumour dissemination and
      adversely affects survival after liver resection.
AB  - BACKGROUND: Liver resection is increasingly being performed for metastatic
      colorectal cancer. This study assessed the need for preoperative biopsy of
      suspected metastases and whether biopsy has any effect on long-term survival.
      METHODS: Prospectively collected data on patients who underwent liver resection
      for colorectal metastases between 1986 and 2003 were reviewed retrospectively.
      The endpoints of morbidity, operative mortality and long-term survival were
      compared between patients who had biopsy before referral (group 1) and those who
      did not (group 2). RESULTS: Patient demographics and disease distribution were
      similar for 90 patients in group 1 and 508 in group 2. Seventeen patients (19 per
      cent) who had undergone biopsy either at the time of colorectal resection or
      radiologically had evidence of needle-track deposits. Operative mortality and
      morbidity rates in the two groups were similar. The 4-year survival rate after
      liver resection was 32.5 (s.e. 5.5) per cent in group 1, compared with 46.7 (2.8)
      per cent in group 2 (P = 0.008). CONCLUSION: Needle-track deposits are common
      after biopsy of suspected colorectal liver metastases. Biopsy of metastases
      confers poorer long-term survival on patients after liver resection and cannot be
      justified in patients with potentially resectable disease.

PMID- 15997445
TI  - Effect of sacral neuromodulation on the rectum.
AB  - BACKGROUND: Sacral neuromodulation (SNM) is a new treatment for faecal
      incontinence. At present the exact underlying mechanism is still unclear.
      Modulation of the sacral reflex arcs might have an effect on rectal sensitivity,
      wall tension and compliance. METHODS: Fifteen consecutive patients with faecal
      incontinence who qualified for SNM underwent barostat measurements before and
      during neuromodulation. An 'infinitely' compliant plastic bag with a volume of
      600 ml was placed in the rectum and connected to a computer-controlled barostat
      system. An isobaric phasic distension protocol was used. Patients were asked to
      report rectal filling sensations: first sensation (FS), earliest urge to
      defaecate (EUD) and an irresistible, painful urge to defaecate (maximum tolerated
      volume; MTV). Rectal wall tension and compliance were calculated. RESULTS: During
      isobaric phasic distension each patient experienced all rectal filling sensations
      at the time of stimulation. Median volume thresholds decreased significantly
      during stimulation, from 98.1 to 44.2 ml for FS (P = 0.003), from 132.3 to 82.8
      ml for EUD (P = 0.001) and from 205.8 to 162.8 ml for MTV (P = 0.002). Pressure
      thresholds tended to be lower for all filling sensations, but only that to evoke
      MTV was reduced significantly by stimulation (37.3 versus 30.3 mmHg; P = 0.005).
      Median rectal wall tension for all filling sensations decreased significantly
      with stimulation. There was no significant difference between compliance before
      and during stimulation. CONCLUSION: SNM affects rectal sensory perception, but
      further research is required to clarify the mechanism.

PMID- 15997446
TI  - Bladder and sexual function following resection for rectal cancer in a randomized
      clinical trial of laparoscopic versus open technique.
AB  - BACKGROUND: Bladder and sexual dysfunction are recognized complications of
      mesorectal resection. Their incidence following laparoscopic surgery is unknown.
      METHODS: Bladder and sexual function were assessed in patients who had undergone
      laparoscopic rectal, open rectal or laparoscopic colonic resection as part of the
      UK Medical Research Council Conventional versus Laparoscopic-Assisted Surgery In
      Colorectal Cancer (CLASICC) trial, using the International Prostatic Symptom
      Score, the International Index of Erectile Function and the Female Sexual
      Function Index. Sexual and bladder function data from the European Organization
      for Research and Treatment of Cancer QLQ-CR38 collected in the CLASICC trial were
      used for comparison. RESULTS: Two hundred and forty-seven (71.2 per cent) of 347
      patients completed questionnaires. Bladder function was similar after
      laparoscopic and open rectal operations for rectal cancer. Overall sexual
      function and erectile function tended to be worse in men after laparoscopic
      rectal surgery than after open rectal surgery (overall function: difference -
      11.18 (95 per cent confidence interval (c.i.) -22.99 to 0.63), P = 0.063;
      erectile function: difference -5.84 (95 per cent c.i. -10.94 to -0.74), P =
      0.068). Total mesorectal excision (TME) was more commonly performed in the
      laparoscopic rectal group than in the open rectal group. TME (odds ratio (OR)
      6.38, P = 0.054) and conversion to open operation (OR 2.86, P = 0.041) were
      independent predictors of postoperative male sexual dysfunction. No differences
      were detected in female sexual function. CONCLUSION: Laparoscopic rectal
      resection did not adversely affect bladder function, but there was a trend
      towards worse male sexual function. This may be explained by the higher rate of
      TME in the laparoscopic rectal resection group.

PMID- 15997447
TI  - Protective defunctioning stoma in low anterior resection for rectal carcinoma.
AB  - BACKGROUND: Anastomotic leak is a serious complication of resection for low
      rectal carcinoma. METHODS: Data from a prospective multicentre study conducted
      between January 2000 and December 2001 were analysed to determine the early
      outcome after low anterior resection in patients with and without a protective
      stoma. The morbidity and mortality rates associated with ileostomy and colostomy
      closure were compared. RESULTS: Eight hundred and eighty-one (32.3 per cent) of
      2729 patients received a protective stoma after low anterior resection. Overall
      anastomotic leak rates were similar in patients with or without a stoma (14.5
      versus 14.2 per cent respectively). The incidence of leaks that required surgical
      intervention was significantly lower in those with a protective stoma (3.6 versus
      10.1 per cent; P < 0.001), as was the mortality rate (0.9 versus 2.0 per cent; P
      = 0.037). Logistic regression analysis showed that provision of a protective
      stoma was the most powerful independent variable for avoiding an anastomotic leak
      that required surgical correction. Seven hundred and twenty-four of the 881
      patients who received a stoma were followed up. The overall postoperative
      morbidity associated with stoma closure was significantly lower for colostomy
      than for ileostomy (15.3 versus 22.4 per cent; P = 0.031). CONCLUSION: A
      protective stoma reduced the rate of anastomotic leakage that required surgical
      intervention, and mitigated the sequelae of such leakage. Colostomy closure was
      associated with less morbidity than closure of an ileostomy.

PMID- 15997448
TI  - Emergency stapled haemorrhoidectomy for haemorrhoidal crisis.

PMID- 15997449
TI  - Symptomatic and functional outcome after laparoscopic reoperation for failed
      antireflux surgery.
AB  - BACKGROUND: The aim was to determine symptomatic and functional outcome after
      reoperative antireflux surgery for recurrent reflux, persistent dysphagia and
      severe gas bloat, using a primarily laparoscopic surgical approach. METHODS: This
      was a retrospective analysis of prospectively collected data from 118 patients,
      of whom 70 had reoperative surgery for recurrent reflux, 35 for dysphagia and 13
      for gas bloat. DeMeester scores before and 1 year after surgery, functional
      symptoms after surgery and overall patient satisfaction were analysed. RESULTS:
      Reoperation was completed laparoscopically in 101 patients (85.6 per cent), in 28
      after previous open hiatal surgery. The operation was converted from an initial
      laparoscopic approach to open surgery in 17 patients. One-year follow-up data
      were available for 104 patients (88.1 per cent). After reoperation for recurrent
      reflux, 84 per cent had a DeMeester heartburn score of zero or one, and 87 per
      cent had a regurgitation score of zero or one. After reoperation for dysphagia,
      21 of 32 patients had a dysphagia score of zero or one, with improvement observed
      in 25. All patients undergoing reoperation for severe gas bloat were satisfied
      with the outcome 1 year after operation. CONCLUSION: Revisional surgery for
      recurrent reflux using a laparoscopic approach offered high rates of success and
      patient satisfaction. Swallowing returned to normal in two-thirds of patients
      after reoperation.

PMID- 15997450
TI  - Quantification of mortality risk after abdominal aortic aneurysm repair.
AB  - BACKGROUND: The study was designed to evaluate the Acute Physiology And Chronic
      Health Evaluation (APACHE) II risk scoring system in abdominal aortic aneurysm
      (AAA) surgery. The aim was to create an APACHE-based risk stratification model
      for postoperative death. METHODS: Prospective postoperative APACHE II data were
      collected from patients undergoing AAA repair over a 9-year interval from 24
      intensive care units (ICUs) in the Thames region. A multilevel logistic
      regression model (APACHE-AAA) for in-hospital mortality was developed to adjust
      for both case mix and the variation in outcome between ICUs. RESULTS: A total of
      1896 patients were studied. The in-hospital mortality rate among the 1289
      patients who had elective AAA repair was 9.6 (95 per cent confidence interval
      (c.i.) 8.0 to 11.2) per cent and that among the 605 patients who had an emergency
      repair was 46.9 (95 per cent c.i. 43.0 to 50.9) per cent. Four independent
      predictors of death were identified: age (odds ratio (OR) 1.05 (95 per cent c.i.
      1.03 to 1.07) per year increase), Acute Physiology Score (OR 1.14 (95 per cent
      c.i. 1.12 to 1.17) per unit increase), emergency operation (OR 4.86 (95 per cent
      c.i. 3.64 to 6.52)) and chronic health dysfunction (OR 1.43 (95 per cent c.i.
      1.04 to 1.97)). The APACHE-AAA model was internally valid, as shown by
      calibration (Hosmer-Lemeshow C statistic: chi(2) = 6.14, 8 d.f., P = 0.632),
      discrimination properties (area under receiver-operator characteristic curve
      0.845) and subgroup analysis. There was no significant variation in outcome
      between hospitals. CONCLUSION: APACHE-AAA was shown to be an accurate risk
      stratification model that could be used to quantify the risk of death after AAA
      surgery. It might also be used to determine the relative impact of ICU over high
      dependency unit care.

PMID- 15997451
TI  - Preoperative plasma N-terminal pro-brain natriuretic peptide as a marker of
      cardiac risk in patients undergoing elective non-cardiac surgery.
AB  - BACKGROUND: Plasma N-terminal pro-brain natriuretic peptide (NTproBNP) is a
      sensitive marker for heart failure. This study tested whether the preoperative
      plasma level of NTproBNP could predict cardiac complications in patients
      undergoing non-cardiac surgery. METHODS: A total of 190 consecutive patients who
      underwent elective non-cardiac surgery that required general anaesthesia were
      studied. In addition to routine preoperative evaluation, a blood sample was taken
      for estimation of plasma NTproBNP concentration. Postoperative cardiac
      complications were defined as cardiac death, acute coronary syndrome, heart
      failure and haemodynamic compromise from cardiac arrhythmias. RESULTS: Fifteen of
      the 190 patients had a cardiac complication: four had acute coronary syndrome and
      13 had congestive heart failure. NTproBNP concentration was significantly higher
      in patients with a cardiac complication; a level greater than 450 ng/l was
      predictive of cardiac complications with a sensitivity of 100 per cent and a
      specificity of 82.9 per cent. Other factors associated with cardiac complications
      were a higher American Society of Anesthesiologists grade, age and clinical
      cardiac impairment, but in a multivariate analysis NTproBNP level was the only
      independent factor. CONCLUSION: Preoperative plasma NTproBNP concentration may be
      an independent predictor of cardiac complications in patients undergoing non
      cardiac surgery.

PMID- 15997452
TI  - Treatment of loculated lactational breast abscess with a vacuum biopsy system.

PMID- 15997453
TI  - Breast-conserving surgery with resection of the nipple-areola complex for
      subareolar breast carcinoma.
AB  - INTRODUCTION: Breast-conserving therapy for centrally located tumours has in the
      past been viewed with reservation, but is now an accepted treatment. There is
      little published evidence, however, to show that it is safe and cosmetically
      acceptable. METHODS: In a prospective investigation carried out between 1996 and
      2002, 44 women had surgery for 45 breast carcinomas with suspected nipple
      involvement. The breast was conserved and the nipple-areola complex removed.
      Secondary mastectomy was performed in three women because the tumour was found to
      reach the resection margin. Forty-one women underwent further observation. The
      mean tumour size at the time of operation was 18 (range 4-50) mm. Six women
      received preoperative chemotherapy. RESULTS: Histologically, there were seven
      preinvasive and 35 invasive cancers. No local failure had occurred at a median
      follow-up of 51 months. Six women developed distant metastasis, of whom five
      died. The mean score for cosmetic results (evaluated on a scale of 1-5 where a
      score of 1 was excellent) was 1.5 for patients and 1.7 for physicians.
      CONCLUSION: Breast-conserving therapy is a safe and cosmetically acceptable
      alternative to mastectomy for subareolar breast cancer.

PMID- 15997457
TI  - Reaction progress kinetic analysis: a powerful methodology for mechanistic
      studies of complex catalytic reactions.
AB  - Reaction progress kinetic analysis to obtain a comprehensive picture of complex
      catalytic reaction behavior is described. This methodology employs in situ
      measurements and simple manipulations to construct a series of graphical rate
      equations that enable analysis of the reaction to be accomplished from a minimal
      number of experiments. Such an analysis helps to describe the driving forces of a
      reaction and may be used to help distinguish between different proposed
      mechanistic models. This Review describes the procedure for undertaking such
      analysis for any new reaction under study.

PMID- 15997459
TI  - Vesicouterine fistula following Cesarean delivery--ultrasound diagnosis and
      surgical management.
AB  - Vesicouterine fistulae are uncommon, with most units reporting 1-5 cases over 5
      15-year periods. To date there has been a paucity of case reports regarding this
      problem and only a few case series. In this report we outline the presentation
      and management of a vesicouterine fistula complicating a repeat Cesarean
      delivery, specifically describing the role of transvaginal ultrasound.

PMID- 15997460
TI  - Hydrogen-bonding motifs in fullerene chemistry.
AB  - The combination of fullerenes and hydrogen-bonding motifs is a new
      interdisciplinary field in which weak intermolecular forces allow modulation of
      one-, two-, and three-dimensional fullerene-based architectures and control of
      their function. This Minireview aims to extend the scope of fullerene chemistry
      to a truly supramolecular level from which unprecedented architectures may
      evolve. It is shown that electronic communication in C(60)-based hydrogen-bonded
      donor-acceptor ensembles is at least as strong as that found in covalently
      connected systems and that hydrogen-bonding fullerene chemistry is a versatile
      concept for the construction of functional ensembles.

PMID- 15997461
TI  - Interaction of the catalytic domain of inositol 1,4,5-trisphosphate 3-kinase A
      with inositol phosphate analogues.
AB  - The levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in the cytoplasm are
      tightly regulated by two enzymes, Ins(1,4,5)P3 3-kinase and type I Ins(1,4,5)P3 5
      phosphatase. The catalytic domain of Ins(1,4,5)P3 3-kinase (isoenzymes A, B and
      C) is restricted to approximately 275 amino acids at the C-terminal end. We were
      interested in understanding the catalytic mechanism of this key family of enzymes
      in order to exploit this in inhibitor design. We expressed the catalytic domain
      of rat Ins(1,4,5)P3 3-kinase A in Escherichia coli as a His- and S-tagged fusion
      protein. The purified enzyme was used in an Ins(1,4,5)P3 kinase assay to
      phosphorylate a series of inositol phosphate analogues with three or four
      phosphate groups. A synthetic route to D-2-deoxy-Ins(1,4,5)P3 was devised. D-2
      Deoxy-Ins(1,4,5)P3 and D-3-deoxy-Ins(1,4,6)P3 were potent inhibitors of the
      enzyme, with IC50 values in the micromolar range. Amongst all analogues tested,
      only D-2-deoxy-Ins(1,4,5)P3 appears to be a good substrate of the Ins(1,4,5)P3 3
      kinase. Therefore, the axial 2-hydroxy group of Ins(1,4,5)P3 is not involved in
      recognition of the substrate nor does it participate in the phosphorylation
      mechanism of Ins(1,4,5)P3. In contrast, the equatorial 3-hydroxy function must be
      present in that configuration for phosphorylation to occur. Our data indicate the
      importance of the 3-hydroxy function in the mechanism of inositol trisphosphate
      phosphorylation rather than in substrate binding.

PMID- 15997462
TI  - Fluorescent multiplex analysis of carrier protein post-translational
      modification.

PMID- 15997463
TI  - Pseudo 3D single-walled carbon nanotube film for BSA-free protein chips.

PMID- 15997464
TI  - Induction of cyclooxygenase-2 expression by allergens in lymphocytes from
      allergic patients.
AB  - Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up
      regulation of COX-2 expression is responsible for increased PG release during
      inflammatory conditions and is thought to be also involved in allergic states. In
      this study, we demonstrate that in human T, B and natural killer lymphocytes from
      allergic patients, COX-2 expression became induced upon cell challenge with
      specific allergens and that this process is presumably IgE dependent and occurs
      after CD23 receptor ligation. This induction took place at both mRNA and protein
      levels and was accompanied by PGD2 release. IgE-dependent lymphocyte treatment
      elicited, in parallel, an activation of the MAPK p38 and extracellular signal
      regulated kinase 1/2, an enhancement of calcineurin (CaN) activity, and an
      increase of the DNA-binding activity of the nuclear factor of activated T cells
      and of NF-kappaB, with a concomitant decrease in the levels of the cytosolic
      inhibitor of kappaB, IkappaB. In addition, specific chemical inhibitors of MAPK,
      such as PD098059 and SB203580, as well as MG-132, an inhibitor of proteasomal
      activity, abolished allergen-induced COX-2 up-regulation, suggesting that this
      process is mediated by MAPK and NF-kappaB. However, induction of COX-2 expression
      was not hampered by the CaN inhibitor cyclosporin A. We also examined the effect
      of a selective COX-2 inhibitor, NS-398, on cytokine production by human
      lymphocytes. Treatment with NS-398 severely diminished the IgE-dependently
      induced production of IL-8 and TNF-alpha. These results underscore the relevant
      role of lymphocyte COX-2 in allergy and suggest that COX-2 inhibitors may
      contribute to the improvement of allergic inflammation through the reduction of
      inflammatory mediator production by human lymphocytes.

PMID- 15997465
TI  - The immune status of Kupffer cells profoundly influences their responses to
      infectious Plasmodium berghei sporozoites.
AB  - Multi-factorial immune mechanisms underlie protection induced with radiation
      attenuated Plasmodia sporozoites (gamma-spz). Spz pass through Kupffer cells (KC)
      before invading hepatocytes but the involvement of KC in protection is poorly
      understood. In this study we investigated whether gamma-spz-immune KC respond to
      infectious spz in a manner that is distinct from the response of naive KC to
      infectious spz. KC were isolated from (1) naive, (2) spz-infected, (3) gamma-spz
      immune, and (4) gamma-spz-immune-challenged C57BL/6 mice and examined for the
      expression of MHC class I and II, CD40 and CD80/CD86, IL-10 and IL-12 responses
      and antigen-presenting cell (APC) function. KC from gamma-spz-immune-challenged
      mice up-regulated class I and costimulatory molecules and produced elevated IL
      12p40, relative to naive KC. In contrast, KC from naive mice exposed to
      infectious spz down-modulated class I and IL-12p40 was undetectable. Accordingly,
      KC from spz-infected mice had reduced APC function, while KC from gamma-spz
      immune-challenged mice exhibited augmented APC activity. The nearly opposite
      responses are consistent with the fact that spz challenge of gamma-spz-immune
      mice results in long-lasting sterile protection, while infection of naive mice
      always results in malaria.

PMID- 15997466
TI  - An integrative approach to CTL epitope prediction: a combined algorithm
      integrating MHC class I binding, TAP transport efficiency, and proteasomal
      cleavage predictions.
AB  - Reverse immunogenetic approaches attempt to optimize the selection of candidate
      epitopes, and thus minimize the experimental effort needed to identify new
      epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on
      the highly specific MHC class I binding event. Methods have also been developed
      for predicting the antigen-processing steps preceding MHC class I binding,
      including proteasomal cleavage and transporter associated with antigen processing
      (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI
      database to show that a method integrating predictions of MHC class I binding
      affinity, TAP transport efficiency, and C-terminal proteasomal cleavage
      outperforms any of the individual methods. Using an independent evaluation
      dataset of HIV epitopes from the Los Alamos database, the validity of the
      integrated method is confirmed. The performance of the integrated method is found
      to be significantly higher than that of the two publicly available prediction
      methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset,
      9% and 10% of all possible nonamers in the HIV proteins must be tested when using
      the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate
      epitopes. This number is reduced to 7% when using the integrated method. In
      practical terms, this means that the experimental effort needed to identify an
      epitope in a hypothetical protein with 85% probability is reduced by 20-30% when
      using the integrated method. The method is available at
      http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at
      http://www.cbs.dtu.dk/suppl/immunology/CTL.php.

PMID- 15997467
TI  - Amelioration of acute graft-versus-host disease by NKG2A engagement on donor T
      cells.
AB  - Acute graft-versus-host disease (aGVHD) remains a major complication of
      allogeneic bone marrow transplantation, which is caused by donor T cells specific
      for host alloantigens. In a murine model, we found that donor T cells expressed a
      natural killer cell inhibitory receptor, CD94/NKG2A, during the course of aGVHD.
      Administration of an anti-NKG2A mAb markedly inhibited the expansion of donor T
      cells and ameliorated the aGVHD pathologies. These results suggested that the
      CD94/NKG2A inhibitory receptor expressed on host-reactive donor T cells can be a
      novel target for the amelioration of aGVHD.

PMID- 15997468
TI  - Activation of human NK cells by plasmacytoid dendritic cells and its modulation
      by CD4+ T helper cells and CD4+ CD25hi T regulatory cells.
AB  - Plasmacytoid dendritic cells (pDC) represent a specialized cell population that
      produce type I interferon (IFN) in response to virus. Although type I IFN is a
      natural killer (NK) cell modulator, a direct role for pDC in coordinating NK cell
      functions has not yet been elucidated in detail, especially in humans. Here we
      report that human pDC, following engagement of Toll-like receptor (TLR) 9, not
      only activate autologous NK cells, as indicated by the induction of CD69
      expression, but also enhance their effector functions, especially cytotoxicity.
      Moreover, they can induce selective proliferation of CD56bright CD16- NK cells.
      This activity can be strongly augmented by the addition of autologous CD4+ CD25-
      T helper cells in an IL-2-dependent fashion. Strikingly, CD4+ CD25hi T regulatory
      (Treg) cells completely abrogate this IL-2-dependent proliferation of NK cells,
      while they are not able to influence NK cell activation or proliferation solely
      induced by pDC. Our data show that TLR9-engaged pDC represent a critical stimulus
      for human NK cells and that CD4+ Th cells and CD4+ CD25hi Treg cells play an
      important role in modulating human NK cell responses.

PMID- 15997469
TI  - Effect of salivary gland extract of Leishmania vector, Lutzomyia longipalpis, on
      leukocyte migration in OVA-induced immune peritonitis.
AB  - Salivary gland extracts (SGE) from Lutzomyia longipalpis potentate L. major
      infection by inducing a Th2 immune response. However, the effect of SGE on the
      effector phase of immune response is not known. Herein, we demonstrate that SGE
      inhibited neutrophil migration in ovalbumin (OVA)-induced peritonitis in
      immunized mice. SGE pretreatment of mice inhibited OVA-induced CD4+ and CD8+ T
      lymphocyte migration. The OVA-induced production of TNF-alpha, IL-1beta and
      leukotriene B4 (LTB4), neutrophil chemotactic mediators in this model, were
      inhibited by SGE. On the other hand, SGE enhanced production of IL-10 and IL-4.
      In naive mice, SGE also blocked LTB4-induced neutrophil migration, but not that
      induced fMLP. Moreover, co-incubation of LTB4 (but not fMLP, TNF-alpha and MIP
      1alpha) with SGE inhibited the ability of LTB4 to induce neutrophil migration in
      vivo and in vitro. Altogether, the results suggest that SGE has anti-inflammatory
      properties that are associated with inhibition of TNF-alpha and LTB4 production
      and/or with the neutrophil chemotactic activity of LTB4. The effectiveness of SGE
      in inhibiting neutrophil migration and inflammatory mediators release in a Th1
      immune inflammatory response model reinforces the need for isolation of the
      compounds responsible for these activities, which could be used as prototypes for
      the development new anti-inflammatory drugs.

PMID- 15997470
TI  - A new strategy for improved secondary screening and lead optimization using high
      resolution SPR characterization of compound-target interactions.
AB  - Biophysical label-free assays such as those based on SPR are essential tools in
      generating high-quality data on affinity, kinetic, mechanistic and thermodynamic
      aspects of interactions between target proteins and potential drug candidates.
      Here we show examples of the integration of SPR with bioinformatic approaches and
      mutation studies in the early drug discovery process. We call this combination
      'structure-based biophysical analysis'. Binding sites are identified on target
      proteins using information that is either extracted from three-dimensional
      structural analysis (X-ray crystallography or NMR), or derived from a pharmacore
      model based on known binders. The binding site information is used for in silico
      screening of a large substance library (e.g. available chemical directory),
      providing virtual hits. The three-dimensional structure is also used for the
      design of mutants where the binding site has been impaired. The wild-type target
      and the impaired mutant are then immobilized on different spots of the sensor
      chip and the interactions of compounds with the wild-type and mutant are compared
      in order to identify selective binders for the binding site of the target
      protein. This method can be used as a cost-effective alternative to high
      throughput screening methods in cases when detailed binding site information is
      available. Here, we present three examples of how this technique can be applied
      to provide invaluable data during different phases of the drug discovery process.

PMID- 15997472
TI  - Crown stays assault charge in spitting case.

PMID- 15997471
TI  - Saskatchewan: new regulations designed to reduce needle-stick injuries.

PMID- 15997473
TI  - Malaysia: Judge refuses to reduce sentence on account of HIV.

PMID- 15997474
TI  - New Zealand: man jailed for lying about HIV status on residency application.

PMID- 15997475
TI  - Scotland: Court orders damages and reinstatement for unjust dismissal.

PMID- 15997476
TI  - South African activists awarded court costs.

PMID- 15997477
TI  - Take your partner by the hand...

PMID- 15997478
TI  - Immunology goes global.

PMID- 15997479
TI  - [From opinions and hypotheses to facts? Trends in fibromyalgia research].

PMID- 15997480
TI  - Advances in antibody-directed enzyme prodrug therapy.
AB  - Antibody-directed enzyme prodrug therapy has demonstrated feasibility as a
      treatment for cancer. Numerous prodrug/drug systems have been developed for
      activation by a variety of enzymes and although many have shown potential in
      preclinical studies, so far only one system has progressed to the clinic.
      Clinical studies have identified issues that were not readily apparent in
      xenograft models, however, these have not been addressed in the development and
      testing of new prodrugs. The issue of immunogenicity arising from the use of non
      human enzymes has also been a major hurdle. The development of recombinant fusion
      proteins provides reproducible and effective antibody-enzyme products that retain
      the necessary specificity for prodrug activation. Advances in molecular,
      structural and systems biology, in combination with bioinformatics, have allowed
      these molecules to be readily manipulated to provide the desired characteristics.

PMID- 15997481
TI  - Quantification of landfill emissions to air: a case study of the Ano Liosia
      landfill site in the greater Athens area.
AB  - Fugitive pollutant emissions from municipal solid waste landfills have the
      potential to cause annoyance and health impacts in the surrounding residential
      areas. The overall objective of this research was to perform an assessment of
      fugitive pollutant emissions and a dispersion analysis downwind of a specific
      landfill site. The study was performed at the closed Ano Liosia landfill site
      which is located in the greater Athens area. The human exposure from priority to
      health-risk pollutants emitted from landfill, such as vinyl chloride and benzene,
      was estimated by the landfill gas emission LandGEM 2.01 software combined with
      the atmospheric long-term dispersion model ISC3-LT. The emission and
      meteorological conditions under which the models were applied referred to the
      worst-case scenario. This scenario was used for the evaluation of the maximum
      human exposure assessed beyond the Ano Liosia landfill towards the residential
      areas. The above scenario provides the minimum downwind distance of the health
      risk zone which is calculated to be equal to 1.5 km from the landfill. Within
      this distance the assessed air pollutant concentration for several air pollutants
      was significantly above the World Health Organization reference lifetime exposure
      health criteria. Finally, the applied methodology was used in the Ano Liosia
      landfill, where atmospheric concentrations of pollutants measured in the field
      were compared with model predictions.

PMID- 15997482
TI  - Prevention of chromate induced oxidative stress by alpha-lipoic acid.
AB  - The parenteral administration of alpha-lipoic acid (LA) protected against
      chromate induced oxidative stress in mouse liver. A shift in Cr induced pro
      oxidant state to antioxidant-state by LA was noteworthy. The degree of protection
      was significant and similar in different LA administration regimens (prior-, co-
      and post- parenteral Cr exposure) explored. An improved status of the tissue
      antioxidants by LA appeared to be the mechanism of mitigation. The results are of
      chemopreventive value and suggest a possible alternative to ascorbic acid for
      abrogation of Cr toxicity.

PMID- 15997483
TI  - [Decubitus ulcers in paraplegics].

PMID- 15997484
TI  - Methicillin-resistant Staphylococcus aureus: clinical manifestations and
      antimicrobial therapy.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a common skin coloniser and
      less commonly causes infection. MRSA colonisation should be contained by
      infection control measures and not treated. MRSA infections cause the same
      spectrum of infection as MSSA infections, i.e., skin/soft tissue infections,
      bone/joint infections, central IV line infections, and acute bacterial
      endocarditis (native valve/prosthetic valve). There is a discrepancy between in
      vitro sensitivity and in-vivo effectiveness with MRSA. To treat MRSA infections,
      clinicians should select an MRSA drug with proven in-vivo effectiveness, i.e.,
      daptomycin. Linezolid, quinupristin/dalfopristin, minocycline, or vancomycin, and
      not rely on in-vitro susceptibility data. For MRSA, doxycycline cannot be
      substituted for minocycline. Linezolid and minocycline are available for oral
      administration and both are also effective in treating MRSA CNS infections.
      Vancomycin is being used less due to side effects, (increasing MICs/resistance,
      VISA/VRSA), and increased VRE prevalence. The most potent anti-MRSA drug at the
      present time is daptomycin. Daptomycin is useful when rapid/effective therapy of
      MRSA bacteraemia/endocarditis is necessary. Daptomycin is also useful to treat
      persistent MRSA bacteraemias/MRSA treatment failures with other drugs, i.e.,
      vancomycin. There is no difference in virulence between MSSA and MRSA infections
      if treatment is started early and with an agent that has in-vivo effectiveness.

PMID- 15997485
TI  - Clinical manifestations, treatment and control of infections caused by
      Clostridium difficile.
AB  - Clostridium difficile should be suspected in patients who present with nosocomial
      diarrhoea. It is more common in the elderly or in patients with a debilitating
      underlying condition who have received antimicrobial agents, and up to 20-25% of
      patients may experience a relapse. The reference method for diagnosis is the cell
      culture cytotoxin test which detects the presence of toxin B in a cellular
      culture of human fibroblasts, but recovering C. difficile in culture allows the
      performance of a ''second-look" cell culture assay that enhances the potential
      for diagnosis. Oral metronidazole (500 mg tid or 250 mg every 6 hrs) and oral
      vancomycin (125 mg every 6 hrs) administered for 1014 days have similar
      therapeutic efficacy, with response rates near 90-97%. C. difficile strains
      resistant to metronidazole and with intermediate resistance to vancomycin have
      been described. The administration of probiotics such as Saccharomyces boulardii,
      Lactobacillus sp. or brewer's yeast for prophylaxis of CDAD remains
      controversial.

PMID- 15997486
TI  - Neoscholastic psychology revisited.
AB  - Beginning around 1879, a Neoscholastic psychology developed, an experimental
      psychology with a soul. Opposed to materialism, it sought to renew Scholastic
      philosophy by incorporating the findings of the natural sciences. Neoscholastic
      psychology is an important chapter in the history of the relationships between
      science and religion in the 20th century. Neoscholastic psychology was both
      experimental and philosophical. This article presents the main accomplishments of
      North American Neoscholastic psychology in academic and applied areas.
      Neoscholastic psychologists championed scientific psychology while insisting on a
      better conception of human nature. Philosophical critiques led to a decline of
      Neoscholasticism; after the 1960s it was no longer official Catholic philosophy.
      Neoscholasticism gave psychologists concerned with philosophical questions
      impetus to turn to phenomenology, existentialism, and humanistic psychology.

PMID- 15997487
TI  - [Development of guideline for cancer mass screening].

PMID- 15997488
TI  - The making of contemporary American psychiatry, part 1: patients, treatments, and
      therapeutic rationales before and after World War II.
AB  - This article, the 1st in a 2-part series, uses patient records from California's
      Stockton State Hospital to unearth the midcentury roots of contemporary American
      psychiatry. These patient records allow the authors to examine 2 transformations:
      the post-World War II expansion of psychiatry to include the diagnosis and
      treatment not only of psychotic patients but also of nonpsychotic patients
      suffering from problems of everyday living, and the 1950s introduction of the
      first psychotropic drugs, which cemented the medical status of these new
      disorders, thus linking a new therapeutic rationale to biological understandings
      of disease. These transformations laid the groundwork for a contemporary
      psychiatry characterized by voluntary outpatient care, pharmacological treatment
      of a wide range of behaviors and distress, and a doctor-patient relationship and
      cultural acceptance of disease that allow psychiatric patients to identify
      themselves as consumers.

PMID- 15997489
TI  - [Development of guideline for colorectal cancer mass screening].

PMID- 15997490
TI  - Sleeping beauties in psychology: comparisons of "hits" and "missed signals" in
      psychological journals.
AB  - Scientific publications tend to be forgotten quickly. A few works, however, are
      still cited 100 years and more after their publication. The author used
      bibliometric methods to compare "hits" (works noticed by the scientific community
      soon after their publication) with "missed signals" (works that went unnoticed
      until much later) by investigating 2 psychological journals founded in the 1890s:
      Zeitschrift fur Psychologie and Psychological Review. All articles that were
      published in either of these journals up to 1920 and cited more than 25 times in
      the Web of Science up to the year 2000 were considered for inclusion in the
      analysis. It emerged that hits corresponded more closely to the focus of
      scientific attention at the time of the publications than missed signals.

PMID- 15997491
TI  - [Laurentius on anatomy].
AB  - Andreas Laurentius wrote Opera anatomica (1593) and Historia anatomica (1600).
      These books were composed of two types of chapters; 'historia' and 'quaestio'.
      His description is not original, but take from other anatomists. 'Historia'
      describes the structure, action and usefulness of the body parts clarified after
      dissection. 'Quaestio' treats those questions which could not be solved only by
      dissection. Laurentius cited many previous contradicting interpretations to these
      questions and choose a best interpretation for the individual questions. In most
      cases, Laurentius preferred Galen's view. Historia anatomica retained almost all
      the 'historia' and 'quaestio' from Opera anatomica, and added some new 'historia'
      and 'quaestio', especially in regard to the components of the body, such as
      ligaments, membranes, vessels, nerves and glands. Other new 'historia' and
      'quaestio' in Historia anatomica concerned several topics on anatomy in general
      to comprehensively analyze the history of anatomy, methods of anatomy, and
      usefulness of anatomy. Historia anatomica reviewed what was anatomy by describing
      in 'historia' what was known and in 'quaestio' what was unresolved. Till now
      Laurentius's anatomical works have attracted little attention because his
      description contained few original findings and depended on previous books.
      However, the important fact that Historia anatomica was very popular in the 17th
      century tells us that people needed non-original and handbook style of this
      textbook. Historia anatomica is important for further research on the propagation
      of anatomical knowledge from professional anatomists to non-professionals in the
      17th century.

PMID- 15997492
TI  - [Okada Kousho and historical material of medical exchange between Japan and China
      in the last part of the Qing dynasty].
AB  - Japanese medical doctor Okada Kousho, who lived in Nagasaki, traveled around
      Shanghai and Suzhou from February to April in 1872. After coming back to Japan,
      he wrote the "KoGo Nikki (Shanghai Suzhou Travel Diary)" based on this travel
      records. This article truly and objectively summarized his experience of the
      Chinese medical world in the last part of the Qing dynasty, and it provides us
      valuable material for studying the history of Chinese medicine and the medical
      exchange between China and Japan.

PMID- 15997493
TI  - [A short biography of Ashihara Kengyo].
AB  - Ashihara Kengyo was one of the most famous acupuncturists of the latter part of
      the Edo period. He wrote the book Shindo Happi on acupuncture theory. He was
      blind, but he was unrivaled when it came to acupuncture. As a result, he became
      the medical doctor for the feudal government and treated the shogun Tokugawa
      Ienari and many daimyos.He was a descendant of Kiso Yoshinaka, who was a famous
      samurai of the Kamakura era. Thus he re-established the Kiso family name, and
      always held a service for his ancestors.I investigated the history of Ashihara
      Kengyo, on the basis of the data I found on "Kisoshi Karoku". As a result, I
      discovered a wooden statute of him and many related historical spots.

PMID- 15997494
TI  - [Self-cultivation and cultural activities of a rural doctor of the late Edo era:
      the example of Tsuji Genjun].
AB  - This monograph aims to clarify the relation of the self-cultivation of a
      traditional doctor to his cultural activities in rural society in the late EDO
      era. The author considered the life history of TSUJI Genjun (a court surgeon of
      the TSUCHIURA Han- one of the feudal clans under the TOKUGAWA shogunate),
      especially in regard to his rural cultural activities. While pursuing his sincere
      medical work, Genjun intently practiced various forms of traditional culture
      work, for example, tanka poetry, Chinese poetry, southern school Chinese
      painting, Japanese calligraphy, and tea ceremony. A characteristic of his
      cultural practices is the fact that he was not only a dilettante but was also
      self-cultured. Genjun's cultural life and his activities show a typical pattern
      of rural intellectuals.

PMID- 15997495
TI  - For young South Africans, opportunities may have unexpected links to sexual
      behavior.

PMID- 15997496
TI  - Odds of penile HPV are reduced for circumcised men and condom users.

PMID- 15997497
TI  - Vitamin A supplementation erases gender disparities in child mortality in Nepal.

PMID- 15997498
TI  - For young Mexican men, having a confidant raises the odds of condom use.

PMID- 15997499
TI  - HIV infection elevates Kenyan sex workers' STI risk,which rises further as
      immunosuppression increases.

PMID- 15997500
TI  - Women's lack of control in relationships may lead to inconsistent condom use.

PMID- 15997501
TI  - Injectable use may increase women's odds of getting chlamydia or gonorrhea.

PMID- 15997502
TI  - Traditional gender roles and intimate partner violence linked in China.

PMID- 15997503
TI  - Conventional gamma and high energy probe for radioguided dissection of metastases
      in a patient with recurrent thyroid carcinoma with (99m)Tc-MIBI and (18)F-FDG.

PMID- 15997504
TI  - Confidentiality: an ethical and legal conundrum for family therapists.
AB  - There are several important issues influencing the holding of confidences in
      family therapy, among them are privacy, family secrets, confidentiality, and
      privileged communication. Clinicians need to be aware that breach of
      confidentiality is considered a high-risk area in clinical practice, which could
      be brought within a "low profile" malpractice configuration by adopting certain
      risk management techniques. Family therapists have an obligation to maintain
      their practice under the guidance of professional ethics, agency
      policies/procedures, and within emerging judicial parameters. The questions of
      confidentiality that confront family therapists have no clear and easy answers
      and the legal dilemma is ever present.

PMID- 15997505
TI  - Liberalism, public policy and the life not worth living: Abraham Lincoln on
      beneficent euthanasia.

PMID- 15997506
TI  - A moral right to physician-assisted suicide.

PMID- 15997507
TI  - What have we achieved? Reviewing AIDS-related law and policy in Australia.

PMID- 15997508
TI  - Sterilization, the mentally incompetent and the courts.

PMID- 15997509
TI  - Some new problems in biomedical regulation.
AB  - The purpose of this paper is to present rather than resolve some new ethical
      problems which are likely to become the subject of public discussion in the near
      future. Some problems likely to be the subjects of extensive debate are: the
      foetal patient, 'home abortifacients' and abortifacient vaccines, the withdrawal
      of life-sustaining treatment, experimentation on 'spare' human embryos, the
      legalization of heroin abuse and the use of anencephalics and the persistently
      comatose as organ donors.

PMID- 15997511
TI  - Current awareness in geriatric psychiatry.

PMID- 15997510
TI  - AIDS: anonymity in donation situations--where public benefit meets private good.

PMID- 15997512
TI  - [Spontaneous hemoperitoneum secondary the jejunoileitis by Anisakis].

PMID- 15997513
TI  - [Dolicosigma and chronic constipation secondary Chagas' disease].

PMID- 15997514
TI  - [Ischemic colitis secondary to bowel obstruction caused by bariolithes].

PMID- 15997515
TI  - Did the 1998 Master Settlement affect prenatal smoking?

PMID- 15997516
TI  - [Diagnostic value of ultrasound in fetal umbilical cord coiling around the head:
      report of 3 cases].

PMID- 15997517
TI  - [Clinical analysis of 2 cases of simultaneous intra- and extra-uterine
      pregnancies after IVF-ET with 2 healthy babies delivered].

PMID- 15997518
TI  - The effect of rising health insurance premiums on employment.

PMID- 15997519
TI  - Article on mitoxantrone-induced extravasation raised useful questions.

PMID- 15997520
TI  - Article on risk modeling addressed little-studied topic.

PMID- 15997521
TI  - The bane of accurate referencing: how to achieve "perfection".

PMID- 15997522
TI  - Clinical trials research: challenges of patient education and informed consent.

PMID- 15997523
TI  - Ethics committees in Germany.
AB  - Because its chemical industry led the world a century ago, the need for control
      over research on humans was recognized first in Germany. Yet effective control,
      in the form of ethics committees, came later than in some other countries. This
      paper reviews the history and present status of German ethics committees.

PMID- 15997524
TI  - Romanian psychiatry in turmoil.

PMID- 15997525
TI  - A curious Polish code of ethics.
AB  - Grave practical difficulties are becoming apparent in the application of the new
      Polish code of medical ethics. Readers may recall (see Bulletin 75) that it was
      approved in rather curious circumstances, and may be unlawful. These authors
      review the code, and argue that it is also morally inconsistent.

PMID- 15997526
TI  - Treating defective neonates in Hungary.
AB  - How to decide which very small or handicapped newborn babies to treat is as much
      a problem in the former communist countries as in the West. Hungarian attitudes
      to the problem are discussed here.

PMID- 15997527
TI  - Revised medical criteria for evaluating genitourinary impairments. Final rules.
AB  - We are revising the criteria in the Listing of Impairments (the listings) that we
      use to evaluate claims involving genitourinary impairments. We apply these
      criteria when you claim benefits based on disability under title II and title XVI
      of the Social Security Act (the Act). The revisions reflect advances in medical
      knowledge, treatment, and methods of evaluating genitourinary impairments.

PMID- 15997528
TI  - Ethical issues in Czech renal failure.
AB  - This paper examines the provision of care for those with renal failure in
      Czechoslovakia, and concludes that a specific law on transplantation is needed.
      It was originally presented at a conference in Bratislava in January 1992.

PMID- 15997529
TI  - Guidelines: egg donation and consent forms.
AB  - Egg donation has caused the Interim Licensing Authority concern in the last year.
      In its latest annual report it has issued additional guidelines on the subject.
      It has also issued a booklet 'Egg Donation: your questions answered' to be given
      to all prospective egg donors. The booklet contains a consent form for egg
      donation. The new guidelines and consent form are reproduced below. Also
      reproduced is the standard ILA consent form for in vitro fertilisation, which all
      licensed IVF units must use.

PMID- 15997531
TI  - Research ethics committee performance remains vary variable.

PMID- 15997530
TI  - Ethics, genetics and science policy.
AB  - Ethical issues raised by recent rapid advances in genetics are being discussed in
      many settings. A version of this paper was read by its author, a Norwegian moral
      philosopher, at a recent symposium celebrating 90 years of the Nobel prize.

PMID- 15997532
TI  - Consumer response to Clothier.
AB  - Considering the importance of the subject on which it reported, it is remarkable
      that there has been so little public discussion of the Clothier report on the
      ethics of gene therapy. Published last January (see Bulletin 75 for its
      conclusions and recommendations) it was open for further comment and discussion
      until May, while the committee has remained in being. There follow three comments
      on the report, from a consumer group, from a social worker, and from a group of
      social scientists.

PMID- 15997533
TI  - Teaching communication skills in medical education.
AB  - A relationship of respect between patient and doctor often depends crucially on
      the communication that occurs. Hence the importance of trying to ensure that
      medical students learn how to talk with patients.

PMID- 15997534
TI  - Clothier: the missing parts.
AB  - A practising social worker provides the second of our commentaries on the
      Clothier Report. She examines its attitudes to disability, its reductionist
      approach, and some of what it left out.

PMID- 15997536
TI  - Shock and disbelief.

PMID- 15997535
TI  - Why transplants don't happen.

PMID- 15997537
TI  - Commentary on Canadian proposals.
AB  - An expert on United Kingdom fertilisation and embryology law comments here on
      recent Canadian proposals, a summary of which appears on pp 8-11.

PMID- 15997539
TI  - Human genes: good, bad and abnormal.
AB  - A lawyer makes a plea for less value-laden language in genetics and explains how
      the use of normal and abnormal as descriptions of genes produces damaging
      labelling.

PMID- 15997538
TI  - In Re J (a Minor)--(Inherent jurisdiction: consent to treatment).
AB  - Although section 8 of the Family Law Reform Act of 1969 gives minors who have
      reached the age of 16 the right to consent to medical, surgical or dental
      treatment, it confers no absolute right on such minors to refuse treatment. In
      exercise of its inherent jurisdiction to protect minors, the Court had power to
      override the refusal of a girl aged 16 to consent to treatment for anorexia
      nervosa. The Court of Appeal so stated in dismissing an appeal by the girl J
      against Mr Justice Thorpe's order, authorising her removal to a specialist unit
      in London for treatment.

PMID- 15997540
TI  - Who may refuse treatment?
AB  - The Court dismissed an appeal by the Official Solicitor acting on behalf of T, an
      unconscious female patient, from a decision of Mr Justice Ward, sitting at
      Nottingham on 14 July, that it was lawful for the doctors responsible for her
      care to administer blood to her in the circumstances that had arisen. Doctors
      faced with an adult patient's refusal to consent to proposed treatment had to
      consider the basis of that refusal, whether the patient had capacity at that time
      to make it and whether the decision was the patient's own, or made under external
      pressure.

PMID- 15997541
TI  - French national committee celebrates.
AB  - Having been established just as Ronald Reagan withdrew funds from its American
      equivalent, the French national bioethics committee is the longest established
      such committee anywhere. Unfortunately it has not had the international influence
      of the American President's Commission largely, on suspects, because it works in
      the wrong language. It has just celebrated its tenth anniversary with a meeting
      at the Sorbonne.

PMID- 15997542
TI  - Physicians participation in capital punishment in New York.

PMID- 15997543
TI  - A time to die: the cases of Nancy Cruzan and Janet Adkins.

PMID- 15997544
TI  - Centers of excellence: combining "Ritz" service with best-of-class outcomes.

PMID- 15997545
TI  - Rediscovering growth: earning profits the old-fashioned way.

PMID- 15997546
TI  - Competing on excellence: 10 strategies.

PMID- 15997547
TI  - Children's hospitals are stable and strong: top trends for 2010.

PMID- 15997548
TI  - Vertical integration and regional networks: are they working?

PMID- 15997549
TI  - Children's hospitals: top 10 trends for 2010.

PMID- 15997550
TI  - [Media violence affects children. Risk of aggressive behavior--mostly among the
      unprivileged, vulnerable children].

PMID- 15997551
TI  - [Infant crying--a safety risk?].
AB  - A Dutch study is described, in which the occurrence of potentially detrimental
      parental actions induced by infant crying were assessed and thereafter related to
      various factors, including the parents' judgment that the crying was "excessive".
      commentary in the same Lancet issue questions whether this might be interpreted
      as a "blaming of the victim" process. Official Swedish and international
      statistics on child abuse, especially a recent UNICEF report, are summarized. The
      co-occurrence of spouse and child abuse is briefly discussed. Southall and co
      workers' report on covert video recordings of life threatening child abuse is
      related, as well as some of the public reactions following it, and a proposed new
      categorization of child abuse.

PMID- 15997552
TI  - [Swedish child health care--a model for other countries].

PMID- 15997553
TI  - [Adolescent medicine--an introduction].

PMID- 15997554
TI  - [Do asylum seeking children receive the care they are entitled to?].

PMID- 15997555
TI  - [When will we see "Physicians without sponsors" in Sweden?].

PMID- 15997556
TI  - [Burdensome rules for clinical trials are not in proportion to benefits for the
      patient].

PMID- 15997557
TI  - [Suicide among young women in Sweden: high numbers in comparison with the rest of
      Europe].

PMID- 15997558
TI  - [The right to die].

PMID- 15997559
TI  - [Marketing and undernourished elderly].

PMID- 15997560
TI  - [The contribution made by Soviet medicine to the victory in the Great Patriotic
      War].

PMID- 15997561
TI  - [Medical support of the 3rd and 2nd Ukrainian front troops during the Vienna
      offensive operation].

PMID- 15997562
TI  - [Military medicine of the 3rd Byelorussian front in the operation "Bagration"].

PMID- 15997563
TI  - [Medical support of the troops during the Eastern-Carpathian operation].

PMID- 15997564
TI  - [Design of software and hardware complex of automated systems for the management
      of the State Sanitary and Epidemiological Surveillance].
AB  - A new information system (IS) - the software and hardware complex for controlling
      the state sanitary-and-epidemiological inspection (SSEI) was created. The system
      represents the aggregate of automated working places of RF MD chief state
      sanitary physician arid specialists from the department of state sanitary-and
      epidemiological inspection of the Main Military Medical Headquarters. They
      interact through communications with working places of specialists from SSEI Main
      Center, chief state sanitary physicians from the Armed Forces, military districts
      (fleets) and RFAF CSSEI. The special software provides automation of the
      following technological processes: operative sanitary-and epidemiological and
      epidemiological monitoring; the epidemiological analysis of infectious diseases;
      the evaluation of quality and efficiency of sanitary-and epidemiological work. At
      present the complex works in the regime of experimental exploitation when the
      adjustment of communications and special software is performed.

PMID- 15997565
TI  - [The characteristic of damaging mechanical factors in modern wars and military
      conflicts].

PMID- 15997566
TI  - [Protection and improvement of health of military personnel as a psychological
      and-pedagogical task].

PMID- 15997567
TI  - [Air and plasma flows and NO-therapy as a new technology used in the practice of
      military treatment-and-prophylactic institutions (Experimental-and-clinical
      substantiation)].

PMID- 15997568
TI  - [The improvement of arrhythmologic aid at the policlinic stage of military
      medical service].

PMID- 15997569
TI  - [The predictors of ischemic stroke in cerebral atherosclerosis and ischemic heart
      disease].
AB  - The complex medical examination was performed in 145 patients admitted to the
      neurological department with initial diagnosis: "ischemic stroke". We compared
      anamnesis, clinical symptoms, laboratory and instrumental findings in the
      patients with verified ischemic stroke and in those without stroke. The
      significant clinical predictors of ischemic stroke were the following: arterial
      hypertension (> 165/ 95 mm Hg) age 64 years and older, circulatory insufficiency,
      diabetes, atrial fibrillation, lower extremity obliterating atherosclerosis,
      pneumosclerosis and pulmonary emphizema.

PMID- 15997570
TI  - [Some aspects of psychologic health of servicemen who participated in cleanup of
      the aftermath of the accident at the Chernobyl Atomic Electric Power Station].

PMID- 15997571
TI  - [The study of interhemispheric organization of long-term memory processes in
      aircraft crew members].

PMID- 15997572
TI  - [Little known pages of the biography of Ia.V.Villie].
AB  - On the base of complex study of archival data and available historical literature
      the stories connected with Yakov Vasilyevich Villie are discussed. The exact date
      of his death is given, the causes of existing contradictions are presented.
      Villie's relations with representatives of our medicine are described. The
      authors also discuss the problem, which was touched in the middle of XX century,
      i. e. the Villie's charge of espionage. Together with famous works of Russian
      authors the materials of foreign investigators devoted to this problem are used.

PMID- 15997573
TI  - [Medical care rendered to the wounded men with major vessel injuries of
      extremities in Russian Army during XVIII-XIX centuries].

PMID- 15997574
TI  - [Death and colors].

PMID- 15997575
TI  - [Medication errors. Preventive measures in neonatal intensive care].
AB  - Medications errors are one on the main problems in the National Health Service.
      The Neonatal Intensive Care Unit (NICU) is a very specific area and newborns are
      highly exposed to the risk of medication errors. MATERIALS AND METHODS: A
      revision of the therapeutic process was started, involving NICU doctors, nurses
      and the pharmacist, to identify problems and implement adequate solutions. The
      main high risk areas identified were: prescription of the drug and its
      transcription on the drug sheet, calculation of drugs dilutions and dosages to be
      administered, fragmentation of tasks (drugs prepared and administered by
      different professionals). RESULTS: The analysis of the process allowed different
      professionals to be aware of the risks and of the importance of standardized
      behaviours; of the implementation of protocols to prevent possible errors. The
      implementation of computerized calculation of dosages of drugs to be infused
      allowed to prevent errors and favoured personalized prescriptions. The
      introduction of the voluntary complaint forms will hopefully allow to have a
      clearer picture of the magnitude of the problem together with data on its nature,
      to identify future appropriate corrective measures.

PMID- 15997576
TI  - [Evaluation of the quality of care provided by the 118 system: questionnaire on
      the perceived quality of emergency care].
AB  - Patients' satisfaction is an important element of quality of care. Only few
      studies assessed patients satisfaction during emergency care. AIM: The aim of
      this study was to assess the patients' perception of the quality of care during
      emergencies and their satisfaction of the patient-nurse interaction. POPULATION:
      Stratified sample of 280 patients cared for by ambulance services between October
      and December 2002. Patients with red codes were excluded. METHODS: Two focus
      groups, one with nurses and one with citizens, were organised to identify items
      relevant for patients' satisfaction. A 14 items questionnaire was designed to
      explore 3 areas; quality of interpersonal care, efficiency and comfort; technical
      area. Patients were interviewed by phone and asked to express their level of
      agreement with each item (1 no agreement-5 perfect agreement). RESULTS: 272
      patients (97.1%) answered the questionnaire. The technical area (effectiveness of
      treatment and waiting time) and efficiency-comfort (information by phone, comfort
      of the chair-stretcher, waiting times for the call) reported a high-very high
      satisfaction (74.3 and 72.2) while the satisfaction for the quality of the
      interpersonal care (information on treatments, reassurance, respect of the
      significant persons) was lower, 67.6%. CONCLUSION: Patients are able to
      distinguish several dimensions of care. The satisfaction is higher for the
      technical components of care thus leaving space for improvement of interpersonal
      care during emergencies.

PMID- 15997577
TI  - [Urologic rehabilitation of urinary incontinence in women. Prospective study on
      techniques for pelvic floor rehabilitation].
AB  - Urinary incontinence is an unresolved problem for many women. Some non
      pharmacological treatments care effectively contribute to its solution. MATERIALS
      AND METHODS: Twenty one women, of whom fourteen were affected by stress
      incontinence and 7 by urge incontinence, were trained to perform specific
      exercises at home, for one month and exposed to 8 electrical stimulations of 20
      minutes each. Women were asked to fill a diary reporting the number of
      incontinence episodes, the volume of urine losses, and the description of the
      event. RESULTS: Eight women did not report any benefit; 5 referred a 50%
      reduction of the loss, and 8 the complete resolution of symptoms. Benefits were
      mainly reported in women with stress incontinence (10/14) 1 woman with urge
      incontinence did non report any benefit. CONCLUSIONS: While these results confirm
      the effectiveness of this intervention in women with urinary incontinence, as
      already suggested in other studies, they also point to the need of larger patient
      population to identify the best clinical setting and the final impact on
      symptoms.

PMID- 15997578
TI  - [The patients' care after lumbar puncture: hydration and bed rest?].
AB  - Headache after cervical or lumbar puncture has long been attributed to early
      mobilization; however, several trials and meta-analysis did not show any benefit
      from bed rest. AIM: The aim of the survey was to describe the patients' care
      after lumbar puncture. METHODS: A phone interview was administered to the head
      nurses of 50 neurological wards of Lumbardy and Veneto Region. RESULTS: All
      patients are kept at bed rest after the procedure from 3 to 24 hours. They are
      hydrated in 45 centres (i.v. or per os) with amounts of fluids ranging from 500
      to 2500 ml. In 14 wards the patients fast until the afternoon, and are allowed
      only fluids. CONCLUSIONS: Although there is no evidence for the use of increased
      fluids or bed rest to prevent post dural puncture headache, these and other non
      evidence based practices continue to be used. Further research is warranted on
      strategies to implement an evidence based patients care.

PMID- 15997579
TI  - [Women and drugs: the results of the ARNO Study].

PMID- 15997580
TI  - [The nurses' role in the management of hospital emergencies: a literature
      review].

PMID- 15997581
TI  - [Eleven years after: S.O.S. for the world].

PMID- 15997582
TI  - [Combat children in Rio de Janeiro].

PMID- 15997583
TI  - [Therapeutic implications of the differentiation of adult stem cells into other
      cell types].
AB  - During last years stem cells have generated a great interest because its
      potential therapeutic use. These are unspecialised cells, with ability to self
      renewal and to differentiate into other cell types, being embryo cells totipotent
      and of restrictive use for ethical reasons, while adult stem cells are
      multipotent and of potential clinical use . Between the latter the best studied
      are the cells of the bone marrow: hematopoietic producing blood cell lines and
      mesenchymal that may be transformed into hepatocytes, chondrocytes, osteocytes,
      adipocytes, cardiocytes and neural cells. Although these facts are promising many
      studies must be done until to get stem cells therapies, as well as verify these
      treatments in animal models. It is believed that in this century besides
      traditional therapies we will have to take into account cell therapies with stem
      cells, in whose development will be very important the scientific, clinical and
      ethical parameters.

PMID- 15997584
TI  - [Eulogy to Professor Dr. Joan Massague Sole].

PMID- 15997585
TI  - [Mechanisms of cytostasis and metastasis].
AB  - TGFbeta signaling controls a plethora of cellular responses in human development
      and disease. Recent cellular, biochemical, and structural studies have revealed
      significant insight into the mechanisms of the activation of TGFbeta receptors,
      the receptor-mediated activation of Smad transcription factors, the Smad-mediated
      regulation of target gene expression, and the negative control of the cell cycle
      by these signals. Loss of TGFbeta cytostatic responsiveness and gain of
      metastastic activity are common alterations of this pathway in cancer. The
      analysis of these normal and altered states is providing new insights into
      physiology, pathology and therapy.

PMID- 15997586
TI  - [Don Quijote, a lucid mad].
AB  - The case of a 50-year-old hidalgo who believed to be transformed into a knight
      errant named Don Quijote is a megalomaniac systematized delusion of
      transformation of the self, a delusion of metamorphosis in reference to the
      patient's own identity. The outward projection of this syndrome produces some
      delusional misidentifications of others, things and animals and include elements
      of a persecutory delusion which increase the grandiosity of the self. At the same
      time the hidalgo was maniac with a pathway of bipolar disorder. The phenomenon of
      donquijotismo is described as the defence of wasted causes and Sancho Panza as an
      illiterate Socrates.

PMID- 15997587
TI  - [Harmony in oncogenesis based on the evidence of the cytoarjic function:
      microoncozoa and results 1944-2004].
AB  - The importance of the external forms (images) to get the real ideas of any thing,
      as being the basis of human knowledge is discussed. If no image, the imagination
      gets up and hundred of creative ideas (good and wrong) arose. Such happens in
      cancer research: too many theories and much darkness. Then, I ask: why sponges,
      sharks and tortoises, e.g., have not change, nor mutate and neither transform in
      millions of years; meanwhile, cells of human breasts, lungs and prostate, e.g.,
      can brake the rule between thirty to fifty years? The characters of each tumour
      are well described, as a constant, once it is identified by analytical
      citological techniques. So, this means that tumours have proper genetic lines, as
      every natural spices has, according to biological laws for development and growth
      of living organisms, both plants and animals. Besides, the author gives
      experimental evidence on the closed similarities he found between certain
      nematodes isolated from bacterial cultures associated to plant tumours and those
      developed in cultures of blood and other materials from Hodgkin lymphoma. The
      nematodes appeared to be related to Ancylostoma duodenale (spices type attached
      to Suborder: Strongilina; family: Strongiloidea). The cytoarjic oikos is a
      concept of ecological niche involved with and the basis of the cytoarjic
      function.

PMID- 15997588
TI  - [Science and economic development].
AB  - In times of great turbulences at a planetary scale, as a result of economic and
      social disparities, of environmental erosion, cultural uniformization and
      progressive weakness of international ethical and legal international
      institutions, the reinforcement of scientific research appears as one of the
      crucial keys to correct the present trends. Increase of knowledge and its
      adequate application are not only the fundamental pillars of the urgent general
      enhancement of the quality of life, but also economic competitiveness is based on
      knowledge. In this communication recent data on the ERA (European Research Area)
      are presented and commented as well as the proposal of a European Fund (of 2000
      million of euros initially) which, administered by a European Research Council,
      would improve the EU trade and productive perspectives and, above all, will avoid
      or reduce the present brain-drain of those who, lacking opportunities in Europe,
      emigrate to other countries, particularly the United States.

PMID- 15997589
TI  - [Mitochondrial apoptosis].
AB  - Silver staining methods, when selective, yield a high-contrast and high
      resolution image in optical microscopy. A classical method for silver
      impregnation of mitochondria has been applied to liver tissue and reveals a
      marked heterogeneity among mitochondria in single cells. This heterogeneity can
      be detected in the optical microscope but is even more evident at the
      ultrastructural level. The differences in staining intensity may reflect
      different stages in the mitochondrial life cycle. The most lightly stained
      mitochondria and the unstained mitochondria also observed with Electron
      microscopy may represent the earliest phase of the mitochondrial life cycle. On
      the other hand, the progressively darker staining and final appearance of
      shrunken mitochondria may reflect the autodissolution process of these
      organelles. Such a process of mitochondrial apoptosis might make sense as a
      preventive pathway for elimination of damaged mitochondria before cytC or other
      proapoptotic factors could be liberated. This method reveals a marker of
      mitochondrial age.

PMID- 15997590
TI  - [The biography of a neuron].
AB  - A summary review of current concepts regarding the major events in the long life
      cycle (the "biography") of a typical human brain neuron, and the main cellular
      and molecular mechanisms involved, is provided. Once born in the embryo, neurons
      never undergo cell division: Their differentiated phenotype, which includes the
      multiple neuronal networks that each cell establishes, is the cumulative result,
      over years of development, if many cell-autonomous (intrinsic) and intercellular
      (extrinsic) signaling events that regulate gene expression. The effect of such
      signals is not just qualitative, but dependent on their precise timing and
      dosage. Moreover, most intercelullar signals are powerfully regulated by tissue
      spatial constraints, or by the patterned bioelectrical activity (spontaneous
      and/or experience-related) of the developing neuronal networks. Thus, a major
      part of the biological information required to build each adult neuron is coded
      by a myriad of temporally-, spatially- or activity-dependent signaling events
      that occur within the developing neuronal networks themselves over a very
      protracted period. These facts cast serious doubt on the biological soundness of
      cell-replacement strategies as substitutes for damaged adult brain neurons.

PMID- 15997591
TI  - [Obesity and thinness in painting].
AB  - The obesity, serious frequenty sanitary problem, cause of complications that
      effects to the expectation of life, with aesthetic repercussion and with an
      increase in the last decades. Admitted the obesity android, gynoide, central or
      abdominal, wide aesthetic repercussion and physiopathologic like
      hyperdislipemias, metabolic alterations (diabetes mellitus, etc...), arterial
      hypertension, column arthrosis and outlying. Ethiopathologics co-factors,
      sedentariness, genotypic predisposition, endocrine alterations and of the leptina
      secretion. Illustrative cases of obesity in the painting of those that
      characteristic models are exposed, from slight grades to intense affecting to
      both genders. The thinness counterpoint of the obesity, multicausal process, less
      frequent than the obesity with aesthetic and psychological repercussion. It is
      the formed aesthetic thinness to the diverse types physiopathologic, without
      forgetting the constitutional and family form and the anorexy, the serial ones to
      disasters, wars, famines, etc..., the mystic thinness of saints and ascetics, and
      the serial one to consuming processes.

PMID- 15997592
TI  - [The obstetrical biography of Queen Isabel the Catholic (medical and historical
      comments on the Queen's pregnancies, births and miscarriages)].
AB  - In commemoration of the 500 year anniversary of Queen Isabel's death, and in
      homage to her memory, the author provides a suggestive biological perspective of
      her majesty from a gynaecological historian's point of view. The author
      highlights the obstetrical episodes that occurred throughout her reproductive
      life and required the implication of various professionals, such the
      "protomedicato" typical of the epoch, experienced midwives, and Ladies in
      Waiting. The most significant obstetrical events were the births of 5 children:
      Isabel, Juan, Juana, Maria and Catalina. Given the Court's transient nature, the
      children were born throughout various geographical areas of the kingdom:
      Palencia, Seville, Toledo, Cardaba and Alcala de Henares. Indeed, she was an
      exceptional woman born to rule and to give birth far and wide throughout the land
      of her People.

PMID- 15997593
TI  - [Management's problems in the extremely low birth weight assistance].
AB  - Due to the advances of the perinatology, the hope of premature life of the big
      premature has been increased considerably in these last years. But for new
      factors that impact in their prevalence, this has increased, and mainly those
      that are born weighing less than 1.000 gr. In this work we present the results
      obtained in the service of obstetrics of the University General Hospital Gregorio
      Maranon. The prevalence has oscilated between 6 and 19/1000 of the attended
      childbirths that add 34.364 between 1995 and 2003, being the stocking the
      11,88/1000. The factors that more impact in these oscilations are the pregnancy
      after attended fecundation, the population of immigrant women, the premature
      break of membranes, the not controlled pregnancy and the pathological pregnancy.
      The fetal survival below the week 25 are still low, around 15%, and later on,
      when the fetus has reached the 750 gr., it ascends abruptly above 70%, coming
      closer to 90% in the week 28. The protocol of our attendance is described excused
      to obtain these results.

PMID- 15997594
TI  - [Molecular imaging for early diagnosis of Alzheimer's disease].
AB  - The progressive aging of the population and the difficulty of diagnosing and
      treating Alzheimer's disease (AD) portends an exponencial increase in the
      prevalence of this illness. One way to approach this social and health problem is
      to develop diagnostic techniques that allow us to detect the disease in its pre
      clinical stages and apply early treatment that can slow down AD advance.
      Molecular imaging, in particular that generated by positron emission tomography
      with 2-fluoro-2 deoxi-D-glucose (PET-FDG) has shown high sensitivity in detecting
      changes in cerebral metabolic activity in the early stages of AD, and allow other
      dementias and physiological changes that accompany normal aging to be
      distinguished from AD.

PMID- 15997595
TI  - [PET in lymphomas: a pattern for the treatment at measure].
AB  - Positron Emission Tomography with FDG (PET-FDG) is a molecular diagnostic imaging
      technique that allows for the detection of tumour lesions based on their
      increased anaerobic glycolytic metabolism. It is acquiring increasing
      significance in oncology. The introduction of PET in the field of lymphomas has
      been slow. The main reasons are: budget limitations, difficulties to perform
      biopsies in all the lesions, absence of a perfect gold standard and reduced
      number of publications with appropriate methodological quality. Several papers
      have appeared in the last 3 years that assess the value of PET-FDG in lymphomas,
      demonstrating the relationship between the results of PET-FDG and survival
      (total, disease free, progression free and relapse free) or between results of
      PET-FDG and relapse average. All of this has great interest in the definition of
      the most appropriate treatment and especially to decide when it is necessary to
      continue with a determined treatment or to stop it, or when an inefficient
      treatment line must be substituted early by another. The main indications are: a.
      Initial staging. b. Assessment in the middle of the treatment for defining the
      response and for detecting residual disease. c. To confirm or exclude the
      doubtful complete remission at the end of the treatment. In these cases CT scan
      shows a residual mass with response superior to 75%. If PET-FDG is negative, the
      most probable diagnosis is complete remission. d. In a certain type of lymphoma
      the situation if the PET-FDG is positive or negative at the end of treatment is
      very different. A negative PET-FDG can predict longer survival (total, disease
      free, relapse free, progression free) and a positive PET-FDG can indicate a
      change in the treatment or the need for more treatment. e. Residual disease
      evaluation in autologous transplantation. Prognostic utility. f. Variable utility
      of PET-FDG depending on the type of lymphoma.

PMID- 15997596
TI  - [New therapeutic strategies on rectal cancer].
AB  - The rectal cancer is a very frequent condition and the second cause of death for
      malignancy, so in male as in female. Different types of rectal cancer and the
      surgical techniques employed for treating this condition are exposed bellow. In
      this paper, the reasons for planning new therapeutic strategies are analyzed, and
      we conclude with the exposition of the protocol and clinic pathway that we
      aplicate for treating the patients with rectal cancer in our own General Surgery
      Service. Finally we expose the standards of quality in this type of surgery.

PMID- 15997597
TI  - [Breast cancer surgery in the third millenium].
AB  - Progress in health education and awareness by women of this disease, together
      with technical and diagnostic progresses, have contributed at the beginning of
      the third millenium to an earlier diagnosis and surgical treatment of breast
      cancer in women. In addition, a better understanding of the biology and
      development of this disease makes possible to achieve high cure rates with
      conservative surgery. This conservative surgery together wuth systematic analysis
      of sentinel adenopathy will allow cure in the future with only ample
      tumorectomies. For the few cases of advanced tumors, neoadjuvant therapies can be
      used; for multicentric cancers treated with total mastectomy, reconstructive
      surgery and prosthetic materials will be applied. Finally, progress in the
      understanding of genetics and advances in the field of tumor markers and
      receptors will help to establish indications for prophylactic syrgery in women
      considered at high risk for this disease.

PMID- 15997598
TI  - Tests of executive functions in first-degree relatives of schizophrenic patients:
      a meta-analysis.
AB  - BACKGROUND: Executive dysfunctions in relatives of schizophrenic patients may be
      trait markers of genetic liability and thus help us to elucidate the aetiology of
      schizophrenia. As a large amount of data has been published, a synthesis through
      a meta-analysis was needed to demonstrate the existence of executive impairments
      in relatives of schizophrenic patients and to assess their magnitude. METHOD: We
      conducted a meta-analysis of articles that compared performances of controls and
      relatives of schizophrenic patients on the four tests most frequently used to
      assess executive functions: the Wisconsin Card Sorting Test (WCST), the Trail
      Making Test (TMT), the Stroop Test and the Verbal Fluency (VF) Test. When needed
      and possible, published data were supplemented with information from the authors.
      After assessing the homogeneity of the data, effect sizes were estimated and
      publication bias was tested by use of funnel plots. RESULTS: Relatives of
      schizophrenic patients performed less well than controls on all executive tests
      analysed. Effect estimates were in the small to moderate range (from 0.26 to
      0.49) for Stroop, WCST and TMT, but were greater for the fluency tests (0.65 for
      phonological and 0.87 for semantic VF). CONCLUSION: Relatives of schizophrenic
      patients appear to have wide, although not severe, executive dysfunctions. As the
      sensitivity of the different tests for impairments in relatives is not the same,
      the choice of test and method used should be carefully assessed.

PMID- 15997599
TI  - Reduced volume of parietal and frontal association areas in patients with
      schizophrenia characterized by passivity delusions.
AB  - BACKGROUND: In patients with schizophrenia, passivity delusions are characterized
      by a difficulty in determining the agency of purposive actions.
      Neuropsychological and functional neuroimaging data suggest that passivity
      delusions are associated with dysfunction of the parietal lobe association
      cortex. METHOD: Cortical volume calculated from magnetic resonance imaging data
      in a group of 12 patients with schizophrenia characterized by motor passivity
      delusions was compared statistically with the cortical volume of 11 patients
      without passivity delusions. RESULTS: Reduced cortical volume was observed in
      parietal and frontal association cortices in the passivity group. CONCLUSIONS:
      These data provide direct evidence for the involvement of the parietal lobe in
      the pathophysiology of passivity delusions in schizophrenia.

PMID- 15997601
TI  - Stopping and changing in adults with ADHD.
AB  - BACKGROUND: A lack of inhibitory control has been suggested to be the core
      deficit in children with attention deficit hyperactivity disorder (ADHD). This
      means that a primary deficit in behavioral inhibition mediates a cascade of
      secondary deficits in other executive functions, such as arousal regulation.
      Clinical observations have revealed that with increasing age symptoms of
      hyperactivity and impulsivity decline at a higher rate than those of inattention.
      This might imply that a deficit in attention rather than a lack of inhibitory
      control is the major feature in adult ADHD. METHOD: To study whether an
      attentional or inhibitory deficit predominates, the stop-signal task and the stop
      change task were presented to 24 adults with ADHD combined subtype and 24
      controls. RESULTS: Relative to controls, the stop-signal reaction time (SSRT) was
      significantly more prolonged than the go-stimulus reaction time (RT) in patients
      with ADHD. This disproportionate elongation of the SSRT was comparable across
      tasks, even though the stop-change task exerted more complex (or at least
      different) demands on the inhibitory system than the stop-signal task. ADHD
      patients had a higher proportion of choice errors, possibly reflecting more
      premature responses. Specifically in the stop-change task, patients had more
      variable choice responses and made more inappropriate change responses, which may
      also reflect enhanced impulsivity. CONCLUSIONS: The results support a core
      deficit in behavioral inhibition in adults with ADHD. We further suggest that
      there is more evidence for a critical role of deficient inhibitory control in
      adults than in children with ADHD.

PMID- 15997600
TI  - Positron emission tomographic imaging of neural correlates of a fear acquisition
      and extinction paradigm in women with childhood sexual-abuse-related post
      traumatic stress disorder.
AB  - BACKGROUND: In the conditioned fear paradigm, repeated pairing of an aversive
      unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned
      stimulus (CS) (e.g. bright light) results in a conditioned fear response to the
      light alone. Animal studies have shown that the amygdala plays a critical role in
      acquisition of conditioned fear responses, while the medial prefrontal cortex
      (including anterior cingulate), through inhibition of amygdala responsiveness,
      has been hypothesized to play a role in extinction of fear responses. No studies
      have examined neural correlates of fear conditioning and extinction in patients
      with post-traumatic stress disorder (PTSD). METHOD: Women with early childhood
      sexual-abuse-related PTSD (n = 8) and women without abuse or PTSD (n = 11)
      underwent measurement of psychophysiological (skin conductance) responding as
      well as positron emission tomographic (PET) measurement of cerebral blood flow
      during habituation, acquisition and extinction conditions. During habituation
      subjects were repeatedly exposed to a blue square on a screen. During
      acquisition, exposure to the blue square (CS) was paired with an electric shock
      to the forearm (US). With extinction, subjects were again exposed to the blue
      squares without shock. On a different day subjects went through the same
      procedure with electric shocks administered randomly in the absence of the blue
      square. RESULTS: Skin conductance responding to the CS was consistent with the
      development of conditioned responses with this paradigm. PTSD patients had
      increased left amygdala activation with fear acquisition, and decreased anterior
      cingulate function during extinction, relative to controls. CONCLUSIONS: These
      findings implicate amygdala and anterior cingulate in the acquisition and
      extinction of fear responses, respectively, in PTSD.

PMID- 15997602
TI  - Internal and external validity of attention-deficit hyperactivity disorder in a
      population-based sample of adults.
AB  - BACKGROUND: Follow-up studies of childhood ADHD have shown persistence of the
      disorder into adulthood, but no epidemiological data are yet available. METHOD:
      ADHD DSM-IV symptoms were obtained by self-report in an adult population-based
      sample of 1813 adults (aged 18-75 years), that was drawn from an automated
      general practitioner system used in Nijmegen, The Netherlands. The structure of
      ADHD symptoms was analysed by means of confirmatory factor analyses. Other data
      used in this report are the General Health Questionnaire (GHQ-28), information
      about the presence of three core symptoms of ADHD in childhood, and about current
      psychosocial impairment. RESULTS: The three-factor model that allowed for cross
      loadings provided the best fit in the entire sample. This result was replicated
      across gender and age subsamples. Inattentive and hyperactivity symptom scores
      were significantly associated with measures of impairment, even after controlling
      for the GHQ-28. Subjects with four or more inattentive or hyperactive-impulsive
      symptoms were significantly more impaired than subjects with two, one and no
      symptoms. The prevalence of ADHD in adults was 1.0% (95% CI 0.6-1.6) and 2.5%
      (1.9-3.4) using a cutoff of six and four current symptoms respectively, and
      requiring the presence of all three core symptoms in childhood. CONCLUSIONS:
      These results support the internal and external validity of ADHD in adults
      between 18 and 75 years. ADHD is not merely a child psychiatric disorder that
      persists into young adulthood, but an important and unique manifestation of
      psychopathology across the lifespan.

PMID- 15997603
TI  - Effectiveness of a two-phase cognitive rehabilitation intervention for severely
      impaired schizophrenia patients.
AB  - BACKGROUND: Several small-N, uncontrolled reports have demonstrated that the
      behavioral technique of attention shaping has significantly increased attention
      span among severely ill schizophrenia patients. METHOD: In this study, we
      evaluated the effectiveness of using an individually administered intervention
      for improving sustained attention, Attention Process Training (APT), followed by
      an attention-shaping procedure within the context of an ongoing skills training
      group. Patients were randomly assigned to receive either the APT and attention
      shaping sequence (n = 18) or equivalent hours of treatment in the same intensive
      behavioral rehabilitation program (n = 13). RESULTS: Results indicated dramatic
      improvements in attentiveness in the cognitive rehabilitation condition compared
      with the control condition, which demonstrated essentially no change in
      attentiveness over the 12 weeks of treatment. The attention-shaping intervention
      appeared to account for the majority of the effect. In contrast to the
      observational data, performance on neuropsychological tests was unaffected by the
      cognitive interventions. CONCLUSIONS: This two-phase intervention demonstrated
      effectiveness in promoting attentive behavior among chronic schizophrenia
      patients with severe attentional impairment.

PMID- 15997604
TI  - One size fits some: the impact of patient treatment attitudes on the cost
      effectiveness of a depression primary-care intervention.
AB  - BACKGROUND: Despite their impact on outcomes, the effect of patient treatment
      attitudes on the cost-effectiveness of health-care interventions is not widely
      studied. This study estimated the impact of patient receptivity to antidepressant
      medication on the cost-effectiveness of an evidence-based primary-care depression
      intervention. METHOD: Twelve community primary-care practices were stratified and
      then randomized to enhanced (intervention) or usual care. Subjects included 211
      patients beginning a new treatment episode for major depression. At baseline, 111
      (52.6%) and 145 (68.7%) reported receptivity to antidepressant medication and
      counseling respectively. The intervention trained the primary-care teams to
      assess, educate, and monitor depressed patients. Twelve-month incremental
      (enhanced minus usual care) total costs and quality-adjusted life years (QALYs)
      were calculated. RESULTS: Among patients receptive to antidepressants, the mean
      incremental cost-effectiveness ratio was dollar 5,864 per QALY (sensitivity
      analyses up to dollar 14,689 per QALY). For patients not receptive to
      antidepressants, the mean incremental QALY score was negative (for both main and
      sensitivity analyses), or the intervention was at least no more effective than
      usual care. CONCLUSIONS: These findings suggest a re-thinking of the 'one size
      fits all' depression intervention, given that half of depressed primary-care
      patients may be non-receptive to antidepressant medication treatment. A brief
      assessment of treatment receptivity should occur early in the treatment process
      to identify patients most likely to benefit from primary-care quality improvement
      efforts for depression treatment. Patient treatment preferences are also
      important for the development, design, and analysis of depression interventions.

PMID- 15997605
TI  - Incidence and distribution of first-episode mania by age: results from a 35-year
      study.
AB  - BACKGROUND: Few epidemiological studies have investigated incidence by age or age
      at onset distributions for mania or bipolar disorder. The current study aimed to
      determine these in a defined area in south-east London, over a 35-year period.
      METHOD: All cases of first-episode mania presenting to psychiatric services in
      Camberwell, south-east London, between 1965 and 1999 were identified. Incidence
      rates by age, using 5-year age-at-onset bands, were estimated and the structure
      of the age-at-onset distribution for first-episode mania was investigated using
      finite mixture distributions (admixture analysis). RESULTS: The incidence of DSM
      IV bipolar I disorder (BP I), first manic episode peaked in early adult life
      (16.38/100,000 population per year in the 21-25 years band) with a much smaller
      peak in mid-life. A two-component normal mixture distribution fitted age at onset
      better than either a single normal distribution or a three-component mixture,
      implying the existence of early and later onset subgroups. The early onset group
      had a stronger family history of bipolar disorder, and showed more acute, severe
      and atypical symptoms during their first manic episode. CONCLUSIONS: The
      incidence of mania peaks in early adult life but there is clear evidence of early
      and later onset subgroups which may represent different forms of disorder.

PMID- 15997606
TI  - Work stress as a risk factor for major depressive episode(s).
AB  - BACKGROUND: Major depression is a prevalent mental disorder in the general
      population, with a multi-factorial etiology. However, work stress as a risk
      factor for major depression has not been well studied. METHOD: Using a
      longitudinal study design, this analysis investigated the association between the
      levels of work stress and major depressive episode(s) in the Canadian working
      population, aged 18 to 64 years. Data from the longitudinal cohort of the
      Canadian National Population Health Survey (NPHS) were used (n = 6663). The NPHS
      participants who did not have major depressive episodes (MDE) at baseline (1994
      1995 NPHS) were classified into four groups by the quartile values of the
      baseline work stress scores. The proportion of MDE of each group was calculated
      using the 1996-1997 NPHS data. RESULTS: The first three quartile groups had a
      similar risk of MDE. Those who had a work stress score above the 75th percentile
      had an elevated risk of MDE (7.1%). Using the 75th percentile as a cut-off, work
      stress was significantly associated with the risk of MDE in multivariate analysis
      (odds ratio = 2.35, 95% confidence interval 1.54-3.77). Other factors associated
      with MDE in multivariate analysis included educational level, number of chronic
      medical illnesses and child and adulthood traumatic events. There was no evidence
      of effect modification between work stress and selected sociodemographic,
      clinical and psychosocial variables. CONCLUSIONS: Work stress is an independent
      risk factor for the development of MDE in the working population. Strategies to
      improve working environment are needed to keep workers mentally healthy and
      productive.

PMID- 15997607
TI  - Suicide rates according to education with a particular focus on physicians in
      Norway 1960-2000.
AB  - BACKGROUND: Suicide rates are higher in certain educational groups. The highest
      rates are generally found in the medical and allied professions, but the
      empirical evidence for high suicide rates may be questionable. This study
      compares the rate of suicide among trained physicians, dentists, nurses, police
      officers and theologians with the rate among other university graduates and the
      general population according to sex, age and time period. METHOD: Census data
      from 1960, 1970, 1980 and 1990 relating to education were linked to suicide as
      cause of death data from Statistics Norway, and followed up for the period 1960
      2000, comprising 46 and 49 million person-years among men and women respectively.
      RESULTS: Physicians still have a higher rate compared with other graduates and
      the general population, both among males [43.0, 95% confidence interval (CI) 35.3
      52.5] and females (26.1, 95% CI 15.1-44.9). Suicide rates increased steeply by
      age among physicians and other graduates, whereas for non-graduates the rate was
      highest in the 40-60 years age group. The suicide rate among female nurses was
      also elevated, whereas police officers seemed to have an intermediate suicide
      risk. The rate among theologians was low (7.0, 95% CI 2.9-16.9). The suicide
      rates in the 1990s were significantly lower than in the 1980s. CONCLUSIONS: The
      high suicide rates among physicians and elderly graduates are of concern. The
      reasons why graduates are more vulnerable than others when getting older and the
      low rate among theologians warrant further study.

PMID- 15997608
TI  - Childhood abuse and familial violence and the risk of panic attacks and panic
      disorder in young adulthood.
AB  - BACKGROUND: The objectives of the study were to examine linkages between exposure
      to childhood abuse and interparental violence and the subsequent development of
      panic attacks and panic disorder using data gathered on a birth cohort of 1265
      New Zealand young people studied to the age of 21 years. METHOD: Data on: (a)
      exposure to child abuse and interparental violence; (b) the development of panic
      attacks and panic disorder; and (c) other childhood and related factors were
      gathered over the course of a 21-year longitudinal study. RESULTS: After
      adjustment for childhood and related factors, exposure to childhood physical
      abuse was associated with a significantly increased risk of later panic attack
      (OR 2.3, 95% CI 1.1-4.9) and panic disorder (OR 3.0, 95% CI 1.1-7.9); childhood
      sexual abuse was associated with a significantly increased risk of panic attack
      (OR 4.1, 95% CI 2.3-7.2) and a marginally significant increase risk of panic
      disorder (OR 2.2; 95% CI 0.98-5.0). Exposure to interparental violence was
      unrelated to later panic attack or disorder after adjustment. CONCLUSIONS:
      Exposure to childhood sexual and physical abuse was associated with increased
      risks of later panic attack/disorder even after adjustment for prospectively
      assessed confounding factors. However, exposure to interparental violence during
      childhood was not related to increased risk of later panic attack/disorder after
      adjustment. These data suggest the need for clinicians to be aware that patients
      with histories of childhood physical and sexual abuse may be at increased risk
      for panic during young adulthood.

PMID- 15997609
TI  - The longitudinal relationship between personality disorder dimensions and global
      functioning in a community-residing population.
AB  - BACKGROUND: Little is known about the long-term outcome of personality disorder
      traits. The purpose of this study was to investigate, in a community-residing
      population, the longitudinal relationship between psychiatrist-assessed
      personality disorder scores and global functioning 13-18 years later. METHOD: A
      stratified random sample of residents of east Baltimore were examined by
      psychiatrists in 1981 and asssessed for DSM-III personality disorders using a
      semi-structured instrument, the Standardized Psychiatric Examination. A total of
      292 persons were re-examined by different psychiatrists during 1994-1999 using
      the Schedules for the Assessment of Neuropsychiatry (SCAN). After completion of
      the SCAN, the subjects' functional status was evaluated using the Global
      Assessment of Functioning (GAF). The relationships between personality dimensions
      and follow-up GAF scores were evaluated using linear regression models. RESULTS:
      All of the personality disorder scales measured in 1981 were inversely related to
      functioning 13-18 years later, with the exception of narcissistic and compulsive
      scales. After controlling for Axis I disorders diagnosed contemporaneously with
      GAF assessment, schizoid, antisocial, borderline, histrionic, and avoidant
      personality disorder scores significantly predicted GAF scores. CONCLUSIONS: Most
      dimensions of DSM-III personality disorder traits were significantly associated
      with global functioning after an interval of 15 years. However, only schizoid,
      antisocial, borderline, histrionic, and avoidant personality disorder traits had
      long-term effects on functioning when Axis I disorders at follow-up were
      controlled. This suggests that the functional effect of the other personality
      disorder traits may be mediated through their relationship with Axis I disorders.
      Future research is needed using more specific and sensitive outcome measures.

PMID- 15997610
TI  - Circulating brain-derived neurotrophic factor is decreased in women with anorexia
      and bulimia nervosa but not in women with binge-eating disorder: relationships to
      co-morbid depression, psychopathology and hormonal variables.
AB  - BACKGROUND: Several lines of evidence indicate a role of the brain-derived
      neurotrophic factor (BDNF) in the modulation of eating behaviour. Therefore,
      alterations in the physiology of this neurotrophin may be involved in the
      pathogenesis of eating disorders. In the present study, we investigated serum
      levels of BDNF in patients with anorexia nervosa (AN), bulimia nervosa (BN) and
      binge-eating disorder (BED). METHOD: Ninety-nine drug-free women (27 with AN, 24
      with BN, 24 with BED and 24 healthy controls) underwent both a blood sample
      collection in the morning and diagnostic and psychopathological assessments by
      means of structured clinical interviews and ad-hoc rating scales. Serum levels of
      BDNF, 17 beta-oestradiol, FT3 and FT4 were measured. RESULTS: Compared to healthy
      controls, serum levels of BDNF were significantly reduced in underweight AN women
      and in normal weight BN women, but not in overweight BED women. Changes in
      circulating BDNF levels were not affected by the presence of co-morbid depressive
      disorders. No significant correlation emerged between neurotrophin concentrations
      and psychopathological, nutritional, demographic and hormonal variables.
      CONCLUSIONS: These findings evidentiate alterations in serum BDNF levels in
      malnourished patients with AN or BN, but not in well-nourished individuals with
      BED. Since BDNF seems to exert a satiety effect, its reduction may represent an
      adaptive change to counteract the decreased calorie ingestion of AN and BN
      individuals.

PMID- 15997611
TI  - Toward an understanding of risk factors for binge-eating disorder in black and
      white women: a community-based case-control study.
AB  - BACKGROUND: This study sought to identify in white women risk factors specific to
      binge-eating disorder (BED) and for psychiatric disorders in general, and to
      compare black and white women on risk factors for BED. METHOD: A case-control
      design was used. Participants were recruited from the community and included 162
      women who met DSM-IV criteria for BED and two comparison groups of women with no
      history of clinically significant eating disorder symptoms. The comparison women
      were matched to BED women on age, education and ethnicity and divided into a
      healthy comparison (HC) group, who had no current psychiatric disorder, and a
      psychiatric comparison (PC) group, who had a diagnosis of a DSM-IV Axis I
      psychiatric disorder. The study sample size was determined by the group with the
      least members (PC), including 107 women with BED and 214 matched comparison
      women. A broad range of risk factors was assessed with a Risk Factor Interview
      and the Parental Bonding Instrument. RESULTS: No significant effects for
      ethnicity by diagnostic group were found. BED women reported higher exposure to
      childhood obesity, family overeating or binge-eating, family discord, and high
      parental demands than PC women. The combined BED and PC group scored
      significantly higher than the HC group on measures of negative affect, parental
      mood and substance disorders, perfectionism, separation from parents, and
      maternal problems with parenting. CONCLUSIONS: These findings indicate that
      childhood obesity and familial eating problems are reliable specific risk factors
      for BED. Ethnicity does not appear to moderate risk for BED.

PMID- 15997612
TI  - Desire for amputation of a limb: paraphilia, psychosis, or a new type of identity
      disorder.
AB  - BACKGROUND: The objective of this paper is to describe and conceptualize an
      unusual and probably rare condition: the intense longstanding desire to have an
      amputation. METHOD: Structured interviews were conducted by telephone of 52
      subjects (mean age: 48.6, range 23-77 years; 47 male, 4 female, 1 intersexed)
      self-identified as having had a desire to have an amputation. RESULTS: Seventeen
      per cent (n = 9) had an arm or leg amputated with two-thirds using methods that
      put the subject at risk of death and one-third enlisting a surgeon to amputate
      their healthy limb. The most common reported reason for wanting an amputation was
      the subject's feeling that it would correct a mismatch between the person's
      anatomy and sense of his or her 'true' self (identity). None were delusional. For
      all but one subject age at onset was during childhood or early adolescence. For
      those who had psychotherapy or medication there was no change in the intensity of
      the desire for amputation. The six subjects who had an amputation at their
      desired site reported that following the amputation they felt better than they
      ever had and no longer had a desire for an amputation. CONCLUSIONS: These
      preliminary results suggest the existence of an extremely unusual clinically
      distinct condition characterized by a lifelong desire to have an amputation of a
      particular limb. The condition is associated with serious negative consequences:
      amputation attempts, impairment and marked distress. Reflecting similarities
      between Gender Identity Disorder and this condition, the author suggests that it
      may be conceptualized as an unusual dysfunction in the development one's
      fundamental sense of anatomical (body) identity.

PMID- 15997613
TI  - Communication and the trauma team.

PMID- 15997616
TI  - Enhancing data quality through the formation of a trauma registry workgroup.

PMID- 15997614
TI  - Delayed splenic rupture: understanding the threat.
AB  - The spleen is the most commonly injured organ in blunt abdominal trauma and is
      also frequently injured as a result of penetrating trauma to the left torso or
      upper abdomen. Most splenic injuries manifest at the moment of injury with
      symptoms of acute intraperitoneal hemorrhage and shock. Delayed rupture of the
      spleen after trauma is an unusual outcome but one that exists. In delayed splenic
      rupture (DSR) there may be an asymptomatic period between initial injury and the
      appearance of signs of internal hemorrhage. Close evaluation of the degree of
      splenic injury by utilizing the Splenic Injury Scale as proposed by the American
      Association for the Surgery of Trauma (AAST), the presence of subcapsular
      hematoma, pseudocyst, or pseudo aneurysm all must be entertained. It is
      imperative that the practitioner caring for this population have a working
      knowledge of the risk factors, diagnostic studies and interventions needed to
      promptly intervene thus reducing the morbidity and mortality associated with the
      splenic trauma and subsequent delayed rupture.

PMID- 15997615
TI  - Advanced Trauma Care for Nurses in Denmark.

PMID- 15997617
TI  - CMS' proposed changes will scale back far reaching provider-based rules.

PMID- 15997618
TI  - ATCN--a door to trauma nursing leadership.

PMID- 15997619
TI  - Management of blunt abdominal trauma in children.
AB  - TOPIC: Over the last decade non-operative management of children with blunt
      abdominal trauma has been established as safe and efficacious. PURPOSE: This
      paper reviews the clinical management and resource utilization patterns in a
      pediatric trauma center in the mid-Atlantic region. It focuses on the following
      issues admission to the intensive care unit, safe interval for activity
      restriction, pre and post imaging with CT, rate of laparotomy and transfusion
      requirements of children with blunt abdominal trauma. Nursing care and medical
      management from the initial evaluation through discharge are discussed. SOURCES:
      Management of blunt abdominal injury in children was restructured using an
      algorithm suggested by the American Pediatric Surgical Association (APSA) trauma
      committee to coordinate care at a regional trauma center. CONCLUSIONS: Results
      indicated a decrease in LOS from 6 days to 4 days, and a 20% reduction in total
      costs.

PMID- 15997620
TI  - A new tool for initial stabilization of pelvic fractures: the TPOD--Trauma Pelvic
      Orthotic Device.

PMID- 15997621
TI  - [Excision of low rectal carcinomas with sphincter preservation. Multimodal
      strategy using neoadjuvant radiotherapy and "delayed" coloanal anastomosis
      without defunctioning stoma].
AB  - Over the past 20 years there have been many advances in the management of rectal
      cancer. The medico-surgical school in Lyon, France, has a long tradition in
      managing this malignancy. The progression of ideas and practices requires a
      better knowledge of the patterns of tumor spread and local recurrence. Technical
      advances have greatly helped to facilitate sphincter preservation. Advances in
      radiotherapy have led to its routine use in the preoperative period. This
      approach has now emerged as the best therapeutic sequence. Our experience
      concerns 46 patients with low rectal carcinoma treated with this strategy. There
      were no post-operative deaths and no leakage. One patient (2%) had a pelvic
      abscess. Median follow-up was 50 months (1-151). At five years, the local
      recurrence rate was 8.5% and the actuarial survival rate was 72%, with a local
      control rate of 91%. Functional outcome, evaluated with a scoring system, was
      good in 60% of cases at one year and 78% at 5 years. Quality of life, evaluated
      with the American Society of Colon and Rectal Surgeons scale (A.S.C.R.S.), was
      107 +/- 21 (range 33-140). The absence of defunctioning stoma (initial or late),
      good sexual and urinary well-being, and psychologic assessment are essential
      factors, requiring rigorous evaluation before the operation and specialized
      management after the operation. The proposed strategy based on this safe
      procedure and "French-type" neoadjuvant radiotherapy, permits sphincter
      preservation in patients with T2 and T3 tumors located near the dentate line,
      with good late oncological outcome. It is often amenable to the laparoscopic
      approach.

PMID- 15997623
TI  - The e-health revolution.

PMID- 15997622
TI  - [Brain natriuretic peptide in acute coronary syndromes: utility of NT-pro BNP
      assay].
AB  - Better risk stratification strategies are required for patients with acute
      coronary syndromes. Plasma myocardial troponin is a specific but poorly sensitive
      marker. Levels of B natriuretic peptide, a 32-amino-acid peptide synthesized and
      released by left ventricular myocytes, correlate strongly both with the presence
      of acute myocardial lesions and with vital outcome. To address the possible
      influence of the sampling time, we measured NT-pro BNP plasma concentrations on
      emergency admission and 8 and 24 hours later in 64 patients with acute coronary
      syndromes. Troponin levels were abnormal in respectively 44%, 51% and 52% of
      patients, while NT-pro BNP levels were abnormal in 75%, 83% and 79% of patients
      (p < 10(-4)). Both troponin and NT-pro BNP levels were abnormal in patients with
      ST elevation MI (n = 15; 93% and 87%, NS) and in patients with non ST elevation
      MI (n = 19; 73% and 68%). In contrast, among 30 patients with unstable angina,
      troponin levels were always normal whereas NT-pro BNP levels were elevated in 73%
      of cases (p < 10(-4)). This suggests that more than 50% patients with acute
      coronary syndromes who have normal troponin levels 8 hours after admission--and
      would therefore be discharged--would qualify for further investigations on the
      basis of natriuretic peptide levels. NT-pro BNP is thus more sensitive than
      troponin as a marker of myocardial damage. In addition, its clinical significance
      is not influenced by the precise sampling time within 24 hours following
      emergency admission. NT-pro BNP therefore adds important information for patient
      stratification.

PMID- 15997624
TI  - [Telomerase and malignant tumors--diagnostic and prognostic role].
AB  - Telomerase synthesizes telomeric DNA repeats at the ends of eukaryotic
      chromosomes and inhibits of natural senescence of different cells. Its increased
      activity has been found in most malignant tumors. This article is a review on
      current knowledge about diagnostic and prognostic value of telomerase in
      malignancies.

PMID- 15997625
TI  - [Endovascular treatment with bifurcated stent-grafts in patients with abdominal
      aortic aneurysms].
AB  - During past few years endovascular procedures at patients with abdominal aorta
      aneurysm (AAA) have widely replaced surgical treatment. The interest put in
      endovascular treatment is high. The number of patients being operated by the use
      of this method has been growing. AIM OF THE STUDY: The objective of this article
      was the evaluation of the results of the endovascular treatment with 42 patients
      with abdominal aorta aneurysms. MATERIAL AND METHODS: All patients (38 men and 4
      women, mean age 65 years) belong to the high risk group. The qualification for
      the endovascular treatment was after the clinical examination and angio-CT,
      abdominal and pelvis digital subtraction angiography (DSA). 36 operations were
      performed under supradural anesthesia and 6 under general anesthesia. Among all
      patients implanted bifurcated abdominal stent-grafts Zenith (COOK) fixing above
      the renal arteries. RESULTS: All operations were ended with success. Some early
      complications were. the leakage to sack of aneurysm, thrombosis of a leg of stent
      graft, the curve of a leg, the growth of the thrombus in stent-graft. All
      patients had the control examinations (abdominal-rtg, pelvis-rtg, USG-color
      Doppler and angio-CT) immediately after the operation and successively after 1, 3
      and 6 months. CONCLUSION: 1. The endovascular procedure among patients with AAA
      by means of bifurcated aortic stent-grafts is in many cases a principal method of
      treatment. 2. Early results of endovascular treatment are good. 3. Longer follow
      up is needed for the evaluation of late results.

PMID- 15997626
TI  - [Assessment of early complications in patients with abdominal aortic aneurysm
      after endovascular operations].
AB  - During past few years endovascular procedures at patients with abdominal aorta
      aneurysm (AAA) have widely replaced surgical treatment. The number of patients
      being operated by the use of this method has been growing. AIM OF THE STUDY: The
      aim of this study is to estimate early complications in patients with AAA treated
      by the use of bifurcated aortic stent-grafts. MATERIAL AND METHODS: Between the
      May 2002 and April 2003, 42 patients were qualified to endovascular operations
      (of the average age of 65). All of them represented a group of high operative
      risk patients. Patients were operated in epidural anesthesia (n=36) and in
      general intravenous anesthesia (n=6). In all the patients angiography was
      performed right after the operation to estimate the efficacy of treatment. The
      follow-up examinations proceeded after 1, 3, and 6 months. RESULTS: During the
      hospitalization, which lasted 7 days on average, clotting in one of the crura of
      the stent-graft in common iliac artery with the necessity of embolectomy, the
      some patient had to have an additional crossover by-pass implanted. There were
      also observed certain post-hospitalization complications which contained: a)
      clotting of stent-graft leg in one case, b) leak type I which demanded
      implantation of additional element of stent-graft in one case c) small leaks type
      I in 2 cases and type II in 2 cases which did not demand any further
      intervention, the type II leaks were observed in 3 cases 6 months after the
      operation, d) the increase of parietal circular thrombus inside the main part of
      the stent-graft in one case, e) complaints connected with the internal iliac
      artery occlusion were declared by one patient. CONCLUSIONS: The early results of
      AAA treatment by the use of bifurcated stent-grafts are satisfactory and
      connected with low rate of complications. Most of the early complications is
      connected with wrong qualification of patients, improper stent-graft choice and
      technical errors during the operation. Constant, periodical follow-up
      examinations (USG, angio CT) are necessary to estimate the late results.

PMID- 15997627
TI  - [Comparison of patients over 70 years old operated for hernia and
      cholecystolithiasis in the years 1990-1994 and 2001-2002].
AB  - THE AIM OF THE STUDY was assessment of this phenomenon as observed in the past
      period of 1990-2002 among patients from the surgical department. In the years
      1990-1994 the percentage of persons over 70 years who had been operated upon rose
      from 14 to 25% with an average of 14.7%. MATERIAL AND METHOD: Patients operated
      for inquinal and femoral hernias and for cholecystolithiasis in the years 1990
      1994 were assessed and compared with those operated in the years 2001-2002 with
      regard to the rate of postoperative complications. RESULTS: It was found that the
      total percentage of patients over 70 years old operated upon became reduced from
      14.7 to 9.7% and that it even fell from 34 to 17% in persons past 80 treated for
      hernia. The marked improvement of the results of the treatment of
      cholecystolithiasis was attributed to the introduction of the laparoscopic method
      of operation. In the group of patients treated with the above method the
      percentage of persons over 80 years old also fell from 19.2 to 12.5%. CONCLUSION:
      This is proof that current demographic data do not always find their reflection
      among persons operated upon and that they do not bear aggravatingly upon the
      results of treatment.

PMID- 15997628
TI  - [Evaluation of the usefulness of imaging techniques in children with urinary
      tract diseases].
AB  - AIM: We assessed the usefulness of imaging diagnostic methods specially
      ultrasonography (USG) in children with urinary tract diseases. MATERIAL AND
      METHODS: Children (n=190, 111-girls and 79 boys) aged from 2 moths to 16 years
      with urinary tract diseases were enrolled in the study. The ultrasonography was
      performed in all subjects and accompanied with voiding cystography in 72, renal
      scintigraphy in 41 and urography in 29 cases. RESULTS: Incorrect ultrasonography,
      voiding cystography, renal scintigraphy and urography were seen in children
      respectively as follows 42/190, 24/72, 38/41, 18/28. Amongst all the methods a
      correlation only between USG and urography was stated. When considering other
      techniques they were complementary in each case. CONCLUSIONS: We conclude that
      the most sensitive method in imaging is renal scintigraphy.

PMID- 15997630
TI  - [Serum gamma-glutamyl transpeptidase activity in children with chronic hepatitis
      B].
AB  - THE AIM OF THE STUDY was evaluation of serum activity of chosen enzymes (ALT,
      AST, GGT and ALP) in assessment of fibrosis degree in children with chronic
      hepatitis B. MATERIAL AND METHODS: We determined serum activity of liver enzymes
      in 47 children aged 4-16 with biopsy-verified chronic hepatitis B, prior to
      interferon alpha treatment. Fibrosis stage was assessed in a blinded fashion
      according to Batts and Ludwig. We defined advanced fibrosis as a score =3.
      Receiver operating characteristics (ROC) analysis was used to calculate the power
      of the assays to detect advanced liver fibrosis (AccuROC, Canada). RESULTS: Serum
      GGT activity of 19 IU/I had a sensitivity of 50% and a specificity of 90%
      (AUC=0.7324, p=0.0391) to predict advanced fibrosis. All other enzymes did not
      allow a useful prediction. CONCLUSION: GGT is suitable serum marker to predict
      advanced liver fibrosis in children with chronic hepatitis B.

PMID- 15997629
TI  - [The evaluation of hyaluronic acid and laminin concentration in serum in children
      with chronic hepatitis B treated with lamivudine, unresponsive to previous
      interferon-alpha therapy].
AB  - THE AIM OF THE STUDY was to evaluate prospectively serum hyaluronic acid (HA) and
      laminin (LAM) concentration in children with chronic hepatitis B (chB) during
      lamivudine treatment. MATERIAL AND METHODS: The observation was carried out on 40
      children (29 boys and 11 girls), aged 4-17 yrs with biopsy proven chB who were
      nonresponders to previous IFN alpha therapy. Lamivudine was given in the dose of
      3-4mg/kg/day up to 100 mg/day. The concentration of HA and LAM were measured with
      EIA technique in serum (CORGENIX and TAKARA kits respectively) before and after
      12 months of therapy. RESULTS: After 12 months of therapy mean serum
      concentration of HA and LAM were lower then before treatment (20.3 +/- 13.3 vs
      26.1 +/- 18.2 ng/ml, p=0.0112; 430 +/- 93 vs 455 +/- 161 ng/ml, p=NS
      respectively). The decrease of HA concentration was observed in subgroups of both
      responders and nonresponders (21.9 +/- 10.9 vs 26.1 +/- 10.6, p=NS; 20.1 +/- 13.7
      vs 26.1 +/- 19.0, p=0.01 resp.). CONCLUSION: The decrease of HA and LAM serum
      concentration may suggest that lamivudine treatment inhibits liver fibrosis.
      Further studies with liver morphology evaluation are needed to confirm
      antifibrotic effect of lamivudine in children with chB.

PMID- 15997631
TI  - [Spirometric evaluation of lung function in patients with myasthenia].
AB  - Effort dyspnoea or dyspnoea at rest are predominating among subjective complaints
      in patients with myasthenia (myasthenia gravis--MG). THE AIM of the study was to
      evaluate the airway function in patients with MG by means of the chosen
      spirometric parameters analysis. MATERIAL AND METHODS: We observed 68 patients
      with MG in which type I (the ocular myasthenia), type IIA (the mild generalized
      form), type IIB (the subacute generalized form) and type IIC (the acute
      generalized form) was diagnosed based on Osserman classification and on 20
      healthy volunteers (control group--CG). The function of the airways was assessed
      by means of "flow-volume" spirometry. RESULTS: The mean values of FEV1, MEF25-75
      i FVC in the type II MG were lower than in CG. The mean value of PEF in the type
      II was lower than in CG and lower than in type I. In the type I of MG the mean
      values of evaluated parameters were not different than in CG. Decrease of PEF
      value was the most often found. The frequency of decreased PEF and FEV1 values
      was higher in type II than in CG. In all types of generalized MG the reduced FVC
      was found more frequently than in healthy people. In each types of MG (the type
      IIA, IIB, IIC) the mean values of the estimated parameters and the frequency of
      the deviation from predicted values were not different. CONCLUSION: The results
      show that in type II of MG the decrease of spirometric parameters is observed
      more often than in healthy people and these abnormalities are most marked in PEF.
      In the ocular MG the distinct tendency to FVC decrease is observed.

PMID- 15997632
TI  - [Impact of 30 day therapy with doxazosin--alpha1 adrenergic blocker on pulmonary
      hemodynamics in patients with secondary pulmonary hypertension due to chronic
      obstructive pulmonary disease].
AB  - To prove alpha1-adrenergic hypothesis for pulmonary hypertension we studied 6
      patients aged 63.3 +/- 8 (range 50-75) years with stable, advanced chronic
      obstructive pulmonary disease (COPD), FEV=1.51 +/- 0.3 I and with pulmonary
      hypertension, mean pulmonary artery pressure 28.3 +/- 8 (range 21-40) mm Hg. a1
      blocker, doxazosin was administered per os in a daily dose of 2-3 mg. Pulmonary
      hemodynamics was performed before and after 30 day of treatment. After therapy,
      compared to baseline results, pulmonary artery systolic pressure decreased from
      48.6 +/- 14 to 42.5 +/- 13 mm Hg, p=0.003, pulmonary artery diastolic pressure
      from 14.5 +/- 6 to 7 +/- 4 mm Hg, p=0.02), mean pulmonary artery pressure from
      28.3 +/- 8 to 21.1 +/- 5 mm Hg, p=0.01 and pulmonary vascular resistance from
      389.6 +/- 14 to 234.6 +/- 73 dyn x s x cm5. No significant changes in pulmonary
      artery wedge pressure, cardiac output, arterial oxygen content, percent
      saturation of hemoglobin with oxygen and oxygen delivery were found. In summary,
      the results of 30 day doxazosin therapy support alpha1 adrenergic hypothesis for
      pulmonary hypertension and suggest potential clinical benefits during long term
      treatment in patients with pulmonary hypertension due to COPD.

PMID- 15997633
TI  - [The use of laser Doppler flowmetry for assessment of skin prick tests with
      histamine solutions and allergens].
AB  - The lately noted growth of the allergy diseases morbidity requires improvement of
      their diagnosis methods. The skin prick test (SPT) is still the most frequently
      applied method in this field. The usually used visual evaluation is sufficient
      for daily practise but unfortunately is not error free. To minimise these errors
      and to make the evaluation more objective an attempt of applying of different
      technics such as LDF has been initiated. AIM: The present study has dealt with
      usefulness of an application of LDF method to evaluate SPT method using different
      allergens, solutions of histamine. MATERIAL AND METHODS: The study was conducted
      on a group of 22 individuals. These individuals underwent SPT with a use of three
      different solutions of histamine (10.0 mg/ml, 1.0 mg/ml, 0.1 mg/ml) and allergens
      and the results of the test were evaluated with an application of the classic and
      LDF methods. RESULTS: Based on the results of the study an optimal distance from
      a prick point and time of the LDF measurement (5 mm, 15 min.) were selected. The
      results of the SPT were analysed with a parallel use of both of the above
      mentioned methods, and the relation between SPT results evaluated by visual
      method and the results obtained with the use of LDF was found. The highest value
      of correlation was obtained for the diameter and area of both--wheal and flare
      for the histamine solution of 1.0 mg/ml, the lower value for 0.1 mg/ml, and the
      lowest for the solution of 10.0 mg/ml and allergen (p < 0.05). CONCLUSION: The
      results of the study shown that the optimal time for evaluation of SPT by LDF
      method is 15 minutes and distance from prick point is 5 mm. In such a case
      correlation between the parameters of visual evaluation and LDF values is most
      significant.

PMID- 15997634
TI  - [Hypotensive effectiveness of therapy combined enalapril and nitrendipine and
      influence on the quality of life].
AB  - It has been proved that effectiveness of monotherapy in mild hypertension is
      about 50%; in the other half of patients the dose of previously used drug should
      be increased or combined therapy should be recommended. THE AIM OF THE STUDY was
      to compare treatment with angiotensin convertase enzyme inhibitor--ACE-I
      (enalapril 10 mg bid--group 1) to therapy with ACE-I combined with calcium
      antagonist (enalapril 5 mg bid + nitrendipine 20 mg qd--group 2). MATERIAL AND
      METHODS: In a prospective, open, randomised crossover study we assessed 44
      hypertensive subjects (17 women, 27 men), aged 35-69 years (mean age 48.6 years)
      with poorly controlled hypertension treated with enalapril 5 mg twice daily. Mean
      initial systolic blood pressure was 150.8 < or = 9.9 mmHg, diastolic 94.7 +/- 5.3
      mmHg respectively. The influence of the treatment regimen on the quality of life
      (QoL) was estimated by a questionnaire. RESULTS: The effectiveness of both used
      procedures did not differ statistically--in both groups mean blood pressure
      reduction was similar (14/8 mmHg in 4 weeks), also percentage of patients with
      well controlled hypertension (about 50%) did not differ significantly. In the
      group with changes regimen from monotherapy to combined therapy the improvement
      of systolic blood pressure was found to be statistically significant (p<0.05); in
      the case of combined therapy replaced with monotherapy such an improvement was
      not observed. In the subgroup with the isolated systolic hypertension combined
      therapy was considerably more effective. The improvement of QoL was noted in both
      groups, mainly in the initial phase of the study. CONCLUSION: In mild
      hypertension ACE-I and calcium antagonist combination is effective in blood
      pressure reduction and in the improvement of the quality of life. Nitrendipine in
      a dose 20 mg in an once daily regimen is a potent and safe hypotensive agent,
      particularly in isolated systolic hypertension.

PMID- 15997635
TI  - [Relationship between plasma brain natriuretic peptide level and left ventricular
      systolic function in coronary artery disease].
AB  - THE AIM of the study was to assess the brain natriuretic peptide (BNP) plasma
      concentrations in patients with CAD and to evaluate the relationships between BNP
      levels and such parameters of the left ventricular (LV) systolic function as
      ejection fraction (LVEF) and peak LV emptying rates (PER). MATERIAL AND METHODS:
      The study population comprised 69 patients with CAD, aged 30-79 years. All
      subjects underwent gated equilibrium radionuclide ventriculography at rest. From
      the data acquired, LVEF and PER were calculated. The plasma BNP concentrations
      were determined in blood samples taken from patients with CAD and in 18 healthy
      subjects and the obtained results were compared with those by radionuclide
      ventriculography. For this purpose patients with CAD were divided into two
      subgroups: dLVEF (LVEF<50%) and nLVEF (LVEF>50%). Subjects with normal LVEF
      (nLVEF) were divided into subgroups with PER greater than median value of this
      parameter and lower than or equal to the median. RESULTS: In patients with CAD
      both the BNP concentration and its frequency were significantly higher than in
      controls. In patients with CAD and dLVEF the BNP concentration was significantly
      higher than in nLVEF cases. Increased BNP concentration was distinctly more
      frequent in dLVEF group than in nLVEF, but the difference was not significant
      (p>0.05). In group with nLVEF, the BNP concentration was higher in patients with
      PER<2.33 (dPER) in comparison to those with PER>2.3 (p>0.05). Not very close, but
      statistically significant correlation was found between the BNP level on the one
      hand and the LVEF and PER on the other. CONCLUSIONS: Increased plasma BNP in
      patients with CAD seem to depend not only on the degree of the myocardial
      contraction, but also on the dynamics of the left ventricular emptying. The
      reason for the BNP elevation in cases with CAD and reduced LV ejection rate but
      normal EF needs to be investigated.

PMID- 15997636
TI  - [Sex hormones, HDL cholesterol and other lipoproteins in older males].
AB  - The associations between sex hormones and cardiovascular risk factors in men are
      controversial. It is well known that testosterone level declines with age and
      this phenomenon is associated with increased incidence of cardiovascular disease
      in men. Elevated levels of total cholesterol and LDL cholesterol together with
      low HDL cholesterol are the important risk factors of coronary heart disease. THE
      AIM OF STUDY was to investigate the relationships between sex hormones and plasma
      lipids in aging males. MATERIAL: The study group comprised 107 males over 50
      years old. RESULTS: A significant positive correlation was found between
      testosterone (T) and HDL-cholesterol (r=0.251; p<0.01). Estradiol level was
      inversely correlated with total cholesterol (r=-0.204; p<0.05). Interestingly,
      the older age of subjects was associated with increased levels of SHBG (r=0.28;
      p<0.01) and decreased free testosterone index (T/SHBG) (r=-0.423; p<0.001).
      CONCLUSION: These data support relationship between sex hormones and plasma
      lipids and suggest that a low testosterone concentration in aging males may be
      important in the pathogenesis of atherosclerosis.

PMID- 15997637
TI  - [Frequency of side effects after botulinum toxin A injections in neurology,
      rehabilitation and gastroenterology].
AB  - Botulinum toxin type A is one of the most potent biological toxins, recently used
      clinically (Botox, Dysport) for wide range of indications. THE AIM OF THE STUDY
      was to assess the frequency and severity of side effects during BTX-A therapy for
      different indications and underlying possible mechanisms. MATERIAL AND METHODS:
      Material consisted of 327 patients (F202, M125) who underwent 1043 sessions of
      BTX-A injections for: cervical dystonia--CD (n=58), blepharospasm--BLP (n=31),
      hemifacial spasm--HFS (n=39), spasticity due to cerebral palsy--CP (n=96),
      chronic anal fissure--CAF (n=96), esophageal achalasia--AE (n=7). RESULTS: In CD
      the following side effects were observed: dysphagia (27% of patients and 7% of
      sessions), weakness of neck muscles (6.7% and 1.3%), pain during swallowing (5.1%
      and 1%), flu-like syndrome (3.4%, 0.7%). Dysphagia appeared 8.2 days after
      injection and lasted 14.9 days on average. In BLP authors noticed: unilateral
      ptosis (22%, 6.3%), bilateral ptosis (3%, 1.9%), haematoma (3%, 0.6%) and in HFS:
      excessive weakness resulting in asymmetry of face--mild (28.2% and 20%) and
      moderate (46% and 26.7%). In spasticity due to CP authors noticed: excessive
      weakness of lower limbs which lasted 13.8 days on average (6.2% and 1.9%), pain
      (5.2% and 1.6%), flu-like syndrome (4.1% and 1.3%). In CAF: mild incontinence of
      the flatus and faeces (9% and 5% of sessions), haematoma (5%), flu-like syndrome
      (3%), inflammation of external anal varices (2%), epididymitis (1%). In AE: chest
      pain in 6 (at the day of injection and lasted 2-4 days) and reflux in 2 patients
      (4-8 weeks after injection, lasted 2-3 weeks) were observed. CONCLUSION: Therapy
      with BTX-A is a very safe procedure, especially when compared with high rate of
      effectiveness of injections. The side effects are transient, mostly local and
      completely reversible.

PMID- 15997638
TI  - [The effect of alcoxyglycerols, squalene and n-3 fatty acid on some innate
      immunity parameters in healthy people].
AB  - BioMarine 570 is well tolerated agent supporting the innate immunity. It was
      isolated from Greenland shark liver. AIM: To evaluate the effect of BioMarine.
      MATERIAL AND METHOD: The 10 healthy, randomly chosen volunteers are included to
      the protocol. Volunteers are given 9 capsules of BioMarine a day for 30 days. The
      clinical and laboratory parameters were analyzed before and after the treatment.
      The following innate immunity parameters were analyzed: C1q, C3 C4 and CH50 of
      complement level, CD4/CD8 ratio, Th1/Th2 cytokine polarization, reactive oxygen
      intermediates production (ROI). RESULTS: Clinically no side effects were noted.
      BioMarine intake has increased the C1q level, increase CD4/CD8 ratio from 1.3 to
      1.8 and polarized Th1/Th2 lymphocyte cytokine secretion towards Th1. The
      modulation of ROI production by neutrophils was also noted. BioMarine has no
      affect on CD4+CD25+ regulatory lymphocytes. CONCLUSION: Concluding BioMarine is
      save, effective and innate immunity supporting agent, can be effectively applied
      in people with disturbed immune system as harmless and effective agent
      normalizing the immune imbalance.

PMID- 15997639
TI  - [Kennedy's disease--case report].
AB  - Kennedy's disease or spinal and bulbar muscular atrophy (SBMA) is a rare
      neurological illness inherited recessively, linked with chromosome X. The first
      symptoms appear in the adult age and result from degeneration of both motor and
      sensory neurons. The disease begins differently, thus causing diagnostic
      mistakes. In our case the symptoms suggested discopathy, therefore the patient
      was operated on L5-S1 discopathy, which did not improve lower limb muscle
      strength. This entailed further diagnostic work-up. The EMG (needle) examination
      showed widespread chronic denervation with reinnervation in the muscles of the
      limbs. The genetic examination revealed increased number of CAG(45) trinucleotide
      repeats, thus confirming a suspicion of Kennedy's disease.

PMID- 15997640
TI  - [Linear nevus sebaceous syndrome with hemimegalencephaly diagnosed in child in
      neonatal period].
AB  - The aim of this study was to present the case of the child with linear nevus
      sebaceous syndrome (LNSS) and hemimegalencephaly, diagnosed in neonatal period.
      It is one of the five epidermal nevus syndromes. Etiology of this multiorgan
      disease is still unknown. Most often LNSS consists of central nervous system,
      skeletal and ocular abnormalities. In present case different epileptic non
      responsive seizures began in second week of life. In image exams
      hemimegalencephaly was found. EEG pattern showed generally discharges. The fits
      responded to vigabatrin. Psychomotor retardation was observed. Sometimes the skin
      lesion may be only manifestation of the syndrome. It is very important to perform
      early image and EEG examinations in LNSS.

PMID- 15997641
TI  - [Severe form of odontogenic sepsis--a case report].
AB  - One of possible and diagnostically difficult sources of bacterial sepsis may be
      purulent foci of odontogenic character. We present the case of a pregnant woman,
      in whom untreated purulent focus within oral cavity led to severe systemic
      infection. The disease was characterized by persistent hectic fever with
      accompanying features of intravascular coagulation, anemia and erythema nodosum
      and no response to antibiotic treatment. It was the second episode of sepsis in
      this patient in a period of one year, the source of the infectious process not
      being recognized previously. Dental examination revealed presence of the apical
      abscess of the tooth 6-, extraction of which led to spectacular clinical
      improvement, accompanied by the healing of erythema nodosum. The clinical course
      and outcome of the disease strongly supports odontogenic etiology, in spite of
      the lack of full microbiological confirmation. Purulent foci within oral cavity,
      including apical abscesses, constitute significant clinical problem and must be
      taken into consideration as a potential source of severe and recurrent systemic
      infections.

PMID- 15997642
TI  - [Structure and function of the glomerular filtration barrier].
AB  - The aim of the review is to discuss recent investigations on the glomerular
      filtration barrier. The barrier consists of three layers: the vascular
      endothelium, the glomerular basement membrane and the slit diaphragm located
      between podocyte foot processes. The main components of the slit diaphragm are
      nephrin, the product of NPHS1 gene and podocin, the product of NPHS2 gene.
      Mutations in NPHS1 lead to congenital nephrotic syndrome of the Finnish type
      (CNF), whereas NPHS2 mutations result in focal segmental glomerulosclerosis
      (FSGS). In both cases massive proteinuria is accompanied by the effacement of
      podocyte foot processess. Reduced expression and redistribution of nephrin and
      podocin are also seen in podocytes of patients with acquired glomerulopathies.
      The results suggest that those proteins play a pivotal role in the processes
      responsible for glomerular filtration. Together with podocin and CD2AP (CD2
      associated protein), nephrin forms a complex determining the integrity of the
      slit diaphragm. Its function has not yet been fully understood and the pathways
      of signal transduction need to be elucidated.

PMID- 15997643
TI  - [The role of free radicals].
AB  - Authors describe action of free oxygenic radicals on human body Syndromes in
      which pathomechanisms free radicals action is probable are listed. Syndromes of
      neonatal period where significant role of free radicals is noted are described:
      bronchopulmonary dysplasia, intraventricular and paraventricular bleedings,
      extracorporeal fibrosis, necrotic enteritis.

PMID- 15997644
TI  - [Molecular indicators of neoplasia in clinical diagnostics].
AB  - In normal conditions growth and cell division processes in tissues and organs are
      precisely regulated. On the molecular level these processes demand coordination
      of protooncogenes, suppressor genes, mismatch repair system genes and apoptotic
      genes expression. Mutations presence leads to alteration or loss of their
      function. In the consequence of these lesions cumulation of DNA errors cumulation
      and loss of cellular proliferation control take place, what leads to genome
      instability and promotes selection of cells clone being able to hyper
      proliferate. Mutations presence in mentioned above groups of genes in high
      percentage had been detecting in cells of neoplasms described in this review.
      According to clinical observations presence of mutations in these genes
      influenced on the clinical course and prognosis. The aim of this review was to
      focus on mutations found in protooncogenes, suppressor genes, mismatch repair
      system and apoptotic genes, which in development of some genetically determined
      neoplasms, some syndromes predisposing to neoplasm development and in some
      sporadic neoplasms in high percentage had been detected. The presence of
      mutations in mentioned above groups of genes as molecular neoplasias indicators'
      in clinical diagnostics had been taking into account.

PMID- 15997645
TI  - [Apoptosis--molecular basis in pathogenesis of selected chronic inflammatory and
      neoplastic diseases].
AB  - Apoptosis is a physiological programmed cell death. The molecular regulation of
      this process is very complex and still unknown. Disregulation in the mechanisms
      controlling apoptosis are thought to be the cause of many diseases. Mutations in
      gene p53 lead to carcinous transformation, high expression of receptor Fas
      increases the cell elimination in chronic inflammatory processes. Wrong balance
      between apoptosis regulatory proteins Bcl-2/Bax is the reason for low mortality,
      radioresistance and chemoresistance. Studies of mechanisms controlling
      interactions between apoptotic proteins will let us find new diagnostic and
      therapeutic methods.

PMID- 15997646
TI  - [The role of radiotherapy in the management of esophageal cancer].
AB  - Surgery remains the standard radical therapy of esophageal cancer. Esophagectomy
      is accompanied by high proportion of morbidity and mortality, and on overall
      provides relatively poor results. Recently in esophageal cancer, radiation
      therapy has been more frequently combined with other modalities including
      chemotherapy and surgery. Survival benefit following preoperative
      chemoradiotherapy was demonstrated in only one randomized trial including
      patients with adenocarcinoma. Similarly, no survival benefit following
      postoperative chemoradiotherapy was demonstrated. Therefore, such two-modality
      strategies are not recommended as a standard management. Definitive radiotherapy
      is indicated in early-stage esophageal cancer patients not amenable to surgery
      because of comorbid conditions, in those who refused surgery, and in selected
      patients with locally advanced disease. Improved survival rates, yet at the
      expense of increased toxicity, were reported by the combining of radiotherapy
      with chemotherapy including 5-fluorouracil and cisplatin. Both brachytherapy and
      external beam radiotherapy are the main palliative approaches in patients with
      dysphagia.

PMID- 15997647
TI  - [Can vulvar carcinoma be a danger in the 21st century?].
AB  - Vulvar carcinoma accounts for 3-5% of all genital cancers. The most common
      histology of vulvar cancer is squamous cell carcinoma. It has been suggested that
      vulvar cancer exists as two separate diseases--HPV-positive, occurring in young
      women, and p53-positive, that occurs in older women. As extensive surgery
      resection is gold standard of treatment, it is important to play attention for
      all symptoms, suggesting the beginning of disease. Understanding of the anatomy
      and the mechanism of lymphatic spread have made modifications in surgical
      technique possible, allowing less radical excisions.

PMID- 15997648
TI  - [Opportunistic protozoa--the problem in immunodeficient patients].
AB  - Protozoan infections with a mild or asymptomatic course in immunocompetent
      individuals, in the case of immunocompromised patients could cause severe
      syndromes or fatal outcome. The different clinical course is possible to diagnose
      only with specific laboratory methods. Actual settlements on the most often
      diagnosed in human opportunistic protozoan infections pathogenesis and
      diagnostics are presented.

PMID- 15997649
TI  - [Bacteriological screening in controlling the spread of methicillin resistant
      Staphylococcus aureus].
AB  - Screening of MRSA carriers can be performed at the time of admission to a
      hospital/a ward or during an outbreak. In this second situation not only patients
      but also medical staff are examined. Because the anterior nares are a major
      reservoir of MRSA, the nasal swab is the most important screening sample.
      Specimens are plated directly on selective media containing fixed concentrations
      of oxacillin or other antimicrobial agents.

PMID- 15997650
TI  - [The role of Chlamydia pneumoniae in the pathogenesis of abdominal aortic
      aneurysm].
AB  - Abdominal aortic aneurysm is a disease with complicated pathogenesis. The known
      risk factors do not explain fully the mechanism of pathological change formation,
      and their modification does not stop but only can retard the illness progression.
      Since an exacerbated inflammation has been detected in the aneurysms wall, the
      hypothesis should be taken under consideration that some role in the disease
      development may play microorganisms. Most attention has been concentrated on
      Chlamydia pneumoniae, bacteria which causes respiratory infection and which
      participation in pathogenesis of atherosclerosis is a subject of a discussion
      that has been carried for years now. Since 1996 there has been presented an
      increased number of proofs (serological studies, in situ detection, in vitro and
      animal-model studies), that the infection of C. pneumoniae is not neutral for the
      process of aneurysm formation. Especially important is the successful attempt of
      bacterial culture from aneurysmal tissue. However, there are still debatable
      issues, which make impossible to give an ultimate answer to the question about
      the relationship between C. pneumoniae and abdominal aortic aneurysm.

PMID- 15997651
TI  - [Lead-induced pathomechanisms of hypertension].
AB  - Based on the literature, the study presents lead-induced mechanisms of
      hypertension development. The investigations performed hitherto, demonstrate that
      exposure to lead causes the damage of endothelial vasodilating function as the
      result of free radicals increase and decrease of the organism antioxidative
      barrier, whereas hormonal and renal mechanisms seem to be secondary phenomenon.

PMID- 15997652
TI  - [Photodynamic therapy in dermatology].
AB  - Photodynamic therapy (PDT) is a therapeutic modality, in which the administration
      of a photosensitizing substances followed by selective irradiation of the lesion
      with visible light leads to destruction of tissues. Authors provide the main
      principles, recent developments, indications and limitations for the use of PDT
      in the treatment of skin diseases.

PMID- 15997653
TI  - [Determination of selected biomarkers can be used in monitoring oxidative stress
      in the course of chronic failure].
AB  - The aim of the study was to assess oxidative stress biomarkers considering the
      simplicity of their determination, invasiveness of material collection and their
      specificity. The following oxidative stress markers were evaluated:
      malonyldialdehyde, thiobarbituric acid reactive lipid peroxidation products,
      prostaglandin F2alpha, nitric oxide derivatives, nucleic acid damage products,
      advanced oxidation protein products and gas components in exhaled air: nitric
      oxide, hydrocarbons, isoprene, ethane. Analysis of the selected biomarkers
      indicates the usefulness of the determination of prostaglandin F2alpha, nucleic
      acid damage products, advanced oxidation protein products and gas components in
      the exhaled air as oxidative stress biomarkers in patients with chronic renal
      failure.

PMID- 15997654
TI  - [Antimicrobial activity of fosfomycin under various conditions against standard
      strains, beta-lactam resistant strains, and multidrug efflux system mutants].
AB  - The purpose of this study was to evaluate the possible benefit of fosfomycin
      (FOM) as prophylactic antibiotic in terms of antimicrobial activity and the
      potential of inducibility of beta-lactamase, compared with cefazolin, cefotiam,
      cefmetazole, and piperacillin that are commonly used as perioperative agents. The
      in vitro activity of FOM against aerobic Gram-negative bacteria using Mueller
      Hinton agar or nutrient agar supplemented with glucose-6-phosphate (G6P) as
      tested medium increased within a range from 2 to 256 times the activity in the
      medium without G6P. However, the susceptibility of Gram-positive bacteria to FOM
      remained largely unchanged with or without G6P. There was no aerobic- or
      anaerobic-bacteria which changed susceptibility against beta-lactam antibiotics
      under various tested medium conditions. FOM demonstrated strong bactericidal
      activity against Escherichia coli and Pseudomonas aeruginosa in a dose dependent
      manner, and decreased viable cell counts of Staphylococcus aureus. In the case of
      P. aeruginosa, transmission electron micrographs study revealed that numerous
      lysed cells were present 2 hours after treatment with FOM at four times the MIC.
      First and second generation cephalosporins induced AmpC-type beta-lactamase in a
      dose dependent manner among beta-lactamase inducible strains of P. aeruginosa and
      Enterobacter cloacae. On the other hand, inducible activity of FOM on beta
      lactamase production was less than 1/25 to 1/65 compared with those of
      cephalosporins. In addition, FOM maintained strong antimicrobial activity for
      over then 20 years after marketing, because of the excellent stability against
      various types of beta-lactamase produced by plasmid-carrying bacteria and
      clinical isolates. FOM was not extruded by four types of efflux systems, such as
      MexAB-OprM, MexCD-OprJ, MexXY/ OprM and MexEF-OprN, however beta-lactam
      antibiotics were substrates of MexAB-OprM and MexCD-OprJ. In conclusion, FOM
      provides adequate coverage for both aerobic Gram-positive and Gram-negative
      bacteria causing postoperative infections. Further, FOM would not
      select/concentrate beta-lactamase producing bacteria in the clinical fields and
      would not be a substrate for multidrug efflux system of P. aeruginosa.

PMID- 15997656
TI  - [The comparison of optimized pharmacodynamic dosing strategy for meropenem using
      Monte Carlo simulation].
AB  - Monte Carlo simulation was enmloyed to determine pharmacodynamic target
      attainment rates for several meropenem dosage regimens against E. coli and P.
      aeruginosa populations. Percent Time above MIC (% T > MIC) exposures for several
      meropenem dosage regimens were simulated for 10,000 subjects. Variability in
      pharmacokinetic parameters and MIC distributions were derived from studies in
      healthy volunteers and the injection antibiotics include of Meropenem
      susceptibility test surveillance program. The probabilities of attaining
      bacteriostatic responses (30% T > MIC) and bactericidal responses (50% T > MIC)
      exposures were high for all dosage regimens against populations of E. coli.
      Against P. aeruginosa, the 1000 g 3.0 infusion q8 dosage regimen provided the
      hightest target attainment rates. Further study of these dosage recommendations
      in clinical trials is suggested.

PMID- 15997655
TI  - [Bacteria isolated from surgical infections and its susceptibilities to
      antimicrobial agents--special references to bacteria isolated between April 2003
      and March 2004].
AB  - Tendency of isolated bacteria from infections in general surgery during the
      period from April 2003 to March 2004 were investigated in a multicenter study in
      Japan, and the following results were obtained. In this series, 455 strains
      including 14 strains of Candida spp. were isolated from 191(75.2%) of 254
      patients with surgical infections. Two hundred and thirty-nine strains were
      isolated from primary infections, and 216 strains were isolated from
      postoperative infections. From primary infections, anaerobic Gram-positive
      bacteria and aerobic Gram-negative bacteria were predominant, while aerobic Gram
      positive bacteria were predominant from postoperative infections. The isolation
      rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and
      Staphylococcus aureus were higher from both types of infections. Among anaerobic
      Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the
      highest from both types of infections. Among aerobic Gram-negative bacteria,
      Escherichia coli was the most predominantly isolated from primary infections,
      followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas
      aeruginosa in this order, and from postoperative infections, E. coli was the most
      predominantly isolated, followed by P. aeruginosa, E. cloacae, and K. pneumoniae.
      Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides
      fragilis group was the highest from both types of infections. The isolation rate
      of anaerobic Gram-positive bacteria from primary infections and that of aerobic
      Gram-positive bacteria from postoperative infections were high in the last
      several years. In this series, we noticed no vancomycin-resistant Gram-positive
      cocci, but a few strains of moderately arbekacin-resistant MRSA. Carbapenm
      resistant P. aeruginosa was seen in less than 10 per cents. Last year we noticed
      that there were cefazolin-resistant E. coli producing extended spectrum beta
      lactamase, but there was no highly cefazolin-resistant E. coli in this year. In
      the next series, increase of both anaerobic bacteria and Enterococcus spp. should
      be carefully followed up.

PMID- 15997657
TI  - [In vitro combined effect of meropenem and various antimicrobial agents against
      beta-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae and
      penicillin-resistant Streptococcus pneumoniae].
AB  - As a basic study of combination therapy for bacterial meningitis, in vitro
      combined effect of meropenem (MEPM) and various antimicrobial agents against beta
      lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR) and
      penicillin-resistant Streptococcus pneumoniae (PRSP) was investigated. The
      following findings were obtained. 1. In the checker board assay using 23 clinical
      isolates of BLNAR, MEPM+cefotaxime (CTX), MEPM+ampicillin (ABPC), and
      MEPM+rifampicin (RFP) showed synergistic effect (21 strains, 6 strains, 4
      strains, respectively) or additive effect (2 strains, 17 strains, 19 strains,
      respectively). 2. In the checker board assay using 19 clinical isolates of PRSP,
      MEPM+CTX, MEPM+teicoplanin (TEIC), and MEPM+RFP showed synergistic effect (5
      strains, 8 strains, 1 strain, respectively), additive effect (14 strains, 11
      strains, 17 strains, respectively) or indifference (0 strain, 0 strain, 1 strain,
      respectively). 3. The time-kill assay with BLNAR demonstrated synergistic
      bactericidal effect of MEPM+CTX and MEPM+RFP, but not MEPM+ABPC. 4. The time-kill
      assay with PRSP demonstrated synergistic or additive bactericidal effect of
      MEPM+CTX, MEPM+TEIC, and MEPM+RFP. 5. There were no antagonistic effect in any
      combination tested in this study. These findings suggest that combination therapy
      with MEPM and various antimicrobial agents tested in this study are useful in
      treating bacterial meningitis caused by BLNAR and PRSP.

PMID- 15997658
TI  - [Synthesis of architectural complex natural products, potent, antibacterial and
      anticancer activity].

PMID- 15997659
TI  - [Application of real-time polymerase chain reaction for the detection of
      prostatic bacteria in patients with chronic prostatitis/chronic pelvic pain
      syndrome].

PMID- 15997660
TI  - [Fecal hydrogen sulfide: toxin? Or just odoriferous gas?].

PMID- 15997662
TI  - [Pharmaceutical marketing in the 21st century].

PMID- 15997661
TI  - [New treatment not based on MIC for infectious diseases--making use of experience
      of macrolide long-term therapy].

PMID- 15997663
TI  - [Epidemiologic, pathologic, diagnostic and clinical features and therapy of
      Helicobacter pylori infection based on latest data].
AB  - Helicobacter pylori is one of the most common human microorganisms. The outcome
      of its acquisition is not predictable, nevertheless a great amount of knowledge
      has accumulated concerning the virulence factors of the bacteria and the diseases
      associated with the infection. In most cases, this indigenous bacterium of the
      human stomach does not cause serious illnesses and the consequences of the
      infection depend on host and environmental factors. A more comprehensive insight
      into bacterial pathogenic and immunogenic mechanisms and host immune response may
      result in a more reasonable, cost-effective therapy and disease prevention.

PMID- 15997664
TI  - [Possibilities for cardiovascular gene therapy].
AB  - Despite recent advances in the management of cardiovascular disease,
      atherosclerotic coronary artery disease has remained a prevalent cause of
      mortality and morbidity among industrialized nations. Although very effective in
      retarding the progression of ischemic heart disease, pharmacotherapies fail to
      provide long-term cardio-protection and to effectively recruit contractile
      function of the damaged left ventricle. Moreover, in many patients the lack of
      compliance to the daily drug administration further reduces the potential benefit
      of these strategies. The recent advent of gene-based approaches, however, may
      represent a potential alternative to target ischemic cardiovascular diseases.
      During the last decade, gene transfer protocols have shown significant
      improvement in experimental and clinical applications, including vascular
      restenosis, chronic peripheral arterial insufficiency, chronic myocardial
      ischemia, myocardial ischemia-reperfusion injury, and congestive heart failure.
      Gene-based therapy using potentially beneficial gene sequences represents a
      promising strategy for site-specific cardiovascular treatment. Transduction of
      host cells may lead to prolonged bioavailability of the transgene product and may
      overcome the need for continuous or repetitive drug administrations. Although
      potential benefits are obvious, they need to be carefully balanced against
      untoward (inflammatory) side effects. In this review, we discuss the significance
      of this novel therapeutic strategy, the lessons we have learned from animal
      studies and how we can envision future use of gene-based strategies in clinical
      practice.

PMID- 15997665
TI  - [Artificial nutrition in acute pancreatitis].
AB  - Nutritional support in acute pancreatitis. Despite increasing knowledge and
      available guidelines in the fields of nutritional support in pancreatic diseases
      there do still exist a lot of controversies, aversions, delusions in the clinical
      work. Hungarian Society of Clinical Nutrition has already published it's own
      guideline on nutrition in pancreatic diseases in 2002. European Society of
      Parenteral and Enteral Nutrition (ESPEN) also published a Consensus Statement
      based on the proposals of an international Consensus Conference with active
      Hungarian participation. The aim of this article is to clear up habitual
      considerations of some physicians and to share current knowledge from
      physiology/pathophysiology to quality control upon these guidelines, meta
      analyses, and, the daily practice of Hungarian pioneers of nutrition support in
      pancreatic diseases.

PMID- 15997666
TI  - [Mesenchymal stem cells as potential source cartilage repair].
AB  - Articular cartilage damaged by disease or trauma has a limited capacity for
      regeneration. The end stage of cartilage loss frequently leads to osteoarthritis
      resulting in a significantly decreased quality of life in millions of people. The
      surgical treatment of articular cartilage injury has always posed difficult
      problems for orthopedic surgeons and regarding long-term outcomes the currently
      available methods are unsatisfactory. The main lack of the applied methods is the
      appearance of the mechanically inadequate resident fibrocartilage instead of
      hyalin cartilage in the place of the cartilage defect. To find reliable methods
      for early repair of cartilage injuries seems of huge importance. Using techniques
      of tissue engineering, artificial cartilage fabricated in vitro has been applied
      for the repair and regeneration of damaged cartilage. Mesenchymal stem cells
      provide a source of cells for the repair of musculoskeletal tissue. Mesenchymal
      stem cells are multipotent cells that are capable of differentiating into
      cartilage, tendon, muscle, cartilage or hematopoiesis supporting marrow stroma.
      To ensure the successful durable integration and function of the engineered
      tissue requires suitable biomechanical and biochemical circumstances, and poses
      the challenge of handling in vitro culture of human cells, cell biology and
      molecular biology.

PMID- 15997667
TI  - [Treatment of peripheral arterial diseases].

PMID- 15997668
TI  - [Vilmos Schulek died 100 years ago].

PMID- 15997669
TI  - [Kalman Frank at the Department of Pediatrics in Pecs (1935-1950)].

PMID- 15997670
TI  - Rapid chromatographic methods for the identification and determination of
      chlorophenoxy herbicides.
AB  - Derivatives of chlorophenoxy carboxylic acids have been the first class of
      herbicides in continuous use since 1947. The main interest for these substances
      is due to their evident chronic toxicity and carcinogenic effect. On the other
      hand, they can cause acute toxicity and have significant role in suicidal
      attempts. In this paper we have investigated analytical approaches that could be
      used for rapid identification and determination of chlorophenoxy herbicides in
      modestly equipped laboratories for the clinical toxicology. Thin layer
      chromatography on cellulose layer using neutral red as ion pairing reagent gave
      the best results in separation of different herbicides, making possible
      visualisation at the daylight without further reagents or equipment. High
      performance liquid chromatography (HPLC) methods for separation on C8 and C18
      phases with and without ion-pairing reagent were compared. It was found that HPLC
      on C18 phase utilising ion-suppression mode has the best reproducibility,
      linearity and mass limit of detection suitable for quantification of
      chlorophenoxy herbicides after acute poisoning.

PMID- 15997671
TI  - [Presence of the muscular bridges and their influence on coronary insufficiency].
AB  - In this work we have analyzed 512 coronary angiograms that were done during 2003
      year at the Clinic for heart diseases and rheumatism of the University of
      Sarajevo Clinic Center (UCCS) and we have dissected 20 human hearts at the
      Institute for Anatomy. We strived to prove frequency of the muscular bridges on
      branches of the coronary artery, their localization and influence on the
      arteriosclerotic changes. Using coronary angiography method we consluded that the
      presence of the muscular bridges in observed population in 4.88% of cases, with
      the most frequent localization on the anterior interventricular branch (ramus
      interventricularis anterior). By dissection method the muscular bridges have been
      found in 55% of cases and the most frequent localization was on the anterior
      interventricular branch and branches of the right coronary artery. Smaller
      frequency of the muscular bridges, shown by the angiography method, can be
      explained by the fact that thick muscular bridges perform weak compression and
      because of that minimal systolic reduction of the lumen which can not be noticed
      by the angiography. The muscular bridges are four times frequent on males and
      they are the most frequent in the age group from 40 to 50 years. In the 88% of
      patients with the muscular bridges were found arteriosclerotic changes localized
      proximately from muscular bridge.

PMID- 15997672
TI  - [Plasma and red blood cell superoxide dismutase activity in patients with
      different stages of essential hypertension].
AB  - It has been suggested that superoxide dismutase (SOD) plays an important role in
      endothelial dysfunction in essential hypertension (EH), by competing with nitric
      oxide for superoxide, thus influencing nitric oxide bioavailability. To answer
      the question of whether endothelial dysfunction is consequence of altered SOD
      expression we determined SOD activity in patients with different stages of EH. In
      this study 45 EH patients and 25 normotensive subjects were included. EH patients
      were divided into the three groups according to the guidelines of European
      Society of Hypertension. SOD activity was determined spectrophotometrically in
      RBC and plasma of EH patients and controls. The results obtained have shown that
      all groups of EH patients exhibit lower SOD activity than control normotensive
      subjects. Significant correlation between SOD activity and both diastolic
      (p<0.05, r=-0.394) and systolic blood pressure (p<0.05, r=-0.356) was found.
      Lowering of SOD activity in patients with different stages of EH leads to
      inefficient detoxification of superoxide in EH. An excess of superoxide of both
      cellular and extracellular origin takes part in enhanced degradation of nitric
      oxide and altered vasodilation, and consequent endothelial dysfunction.

PMID- 15997673
TI  - [Operative treatment of the vestibular schwannoma (acoustic neuroma): correlation
      between the microsurgical approach and cranial nerve lesion].
AB  - INTRODUCTION: Vestibular schwannoma (VS) is a benign tumour of cerebellopontine
      angle which total microsurgical resection is considered as a complex surgery. In
      Bosnia, VS microsurgical resection is performed occasionally and exclusively at
      the University Neurosurgical Depart. in Sarajevo, but radiosurgery of these
      tumours is completely absent. METHODS AND RESULTS: The role of microsurgery in
      resection of VS is being presented. Through analyzed series of operated patients
      (MJLink), we evaluated the correlation of VII and VIII nerves postoperative
      lesion with different operative approaches. House-Brackmann grading scale is used
      for VII nerve deficit appraisal. Current postoperative results of recognized
      experts are compared with our series and the similar morbidity rates are found.
      DISCUSSION: Microsurgery is a dominant and superior way of VS treatment. However,
      the most frequently used microsurgical approaches (retrosigmoid,
      translabyrinthine and extradural subtemporal) are still connected with certain
      morbidity rate, especially regarding the postoperative VII and VIII nerves
      lesion. CONCLUSION: Team approach, intraoperative cranial nerves monitoring and
      microsurgery with utilizing different surgical approaches optimize the outcome of
      VS neurosurgical treatment. In Bosnia, we are just stepping in the field of
      serious approach to this problem.

PMID- 15997674
TI  - Alcohol abuse and risk behavior among adolescents in larger cities in Bosnia and
      Herzegovina.
AB  - OBJECTIVE: To investigate adolescents who abuse drugs and to describe aspects of
      risk behavior among alcohol abusers. METHOD: study was conducted on 598
      adolescents, aged 12-17 years, with equal distribution in rural and urban areas.
      Study was based on self-reported questionnaire Q 2000. Study designed as
      prospective, epidemiological, analitical. Results have been compared within
      groups, between cantons and among groups. Evaluation of data was done using EPI
      info software, with standard statistic methods. RESULTS: Out of the total number
      of 598 adolescents 15.55% had abused alcohol (urban 62.4%, rural 37.6%); 6.69%
      tobacco (urban 67.5%, rural 32.5%); 3.34% cannabis (urban 70.0%, rural 30.0%).
      Results show various aspects of risk behavior among adolescents who consume
      alcohol such as: truancy 44.1%; low success at school 14.0%; suicidal thoughts
      36.6%; unprotected sex 17.7%; drunken driving 10.0%; non use of seat belts 24.7%;
      deliquency (stealing) 22.2%; destructive behavior 18.9%. Adolescents who abuse
      drugs have planned to continue with similar behavior in the future: to abuse
      drugs 31.6%; to smoke 52.2%, to drink alcohol 44.4%, to fight 27.8%; to drive
      without seat belt 36.8%; to have unprotected sex 16.7%. Risk behavior related to
      cannabis abuse and tobacco smoking is also described. CONCLUSION: Data suggests
      that major aspects of adolescents' risk behavior is related to alcohol abuse,
      what should be considered while designing prevention activities and programmes.

PMID- 15997676
TI  - [Parental attitude to psychoactive drug use in adolescents].
AB  - Drug abuse is a problem worldwide, that destroys ones social, economical and
      family life. Our country is in a transition period and consist of postwar
      society. Therefore all risk factors for supstances abuse are present here such as
      social, economical, medical. Parental impact and peers seems to have strong
      impact on adolsecent with almost the same epidemiological characteristics in
      economical developed and undeveloped coutries. To find all risk factors is
      necessary for appropriate prevention approach. The aim of this investigation is
      finding some aspects of parenteral attitude related to drug abuse among early
      adolescents. Research covers 600 participants. Adolescents are equal gender and
      age distribution. It was used Q 2000 as research tool. Study design is
      prospective, epidemiological, analytica. Results showes that out of total number
      of adolescents (600) 15.55% were abusing alcohol, 6.69% smoke, 3.34% use
      cannabis. Parental impact and attitude which is presented in this study related
      to adolescent's drug abuse could be use as base for preventive activities.

PMID- 15997675
TI  - [Efficiency of the short group psychotherapy in rehabilitation of female's
      victims of war sexual torture].
AB  - AIM: Aim is to show the efficiency of short group psychotherapy of females
      victims of war sexual torture, suffering from chronic consequences of torture.
      METHOD: 15 female's victims of war sexual torture were included in this research,
      all of them suffering from chronic consequences of torture. Before including into
      group psychotherapy all of them were interviewed by psychiatrist. Initial testing
      was done before beginning of group psychotherapy with following instruments.
      General Questionnaire, MANSA Questionnaire for registration of Quality of life,
      and Multidimensional Instrument for assessment of psychological symptoms SCL R
      53. Short group psychotherapy lasted three (3) month. Sessions were organized
      weekly and lasted 90 min. Group was leaded by two cotherapists both female.
      Working technique was supportive-expressive psychotherapy. During the group
      psychotherapy cycle clients have received general medical treatment,
      physiotherapy, gynecological treatment and dental treatment. When indicated they
      were treated with medications. After three month of therapy they were retested
      with MANSA and SCL-53 Questionnaires. RESULTS: Retest results after three month
      of treatment on MANSA Questionnaire are showing the significant improvement of
      quality of life. On SCL-53 Questionnaire there is reduction in all
      psychopathological symptoms, except on scale of obsessive compulsive symptoms,
      but it is statistically significant on subscale of paranoid ideation p<0.05, and
      on subscale of anxiety is on the border of significance p=0.054. CONCLUSIONS:
      Short group psychotherapy has shown efficiency in treatment of chronic
      psychological consequences with the females victims of sexual torture in the war.
      Chronic psychological consequences of torture are reduced after three month of
      treatment. Group experience helped to sexual torture survivor's to establish the
      better quality of life.

PMID- 15997677
TI  - [Comparison of the urodynamic stop-flow test and degree of obstruction in
      prediction of postprostatectomy outcome].
AB  - OBJECTIVE: to compare predictive value of urodynamic parameters (level of
      obstruction and stop-flow test) to post prostatectomy outcome. SAMPLE AND
      METHODOLOGY: 30 patients elected for prostatectomy based to the patient's
      symptoms, radiological signs of benign prostate enlargement and signs of the
      retention of urine. All patients underwent complete UDM-uroflowmetry, cystometry
      and pressure/flow studies, after fulfilling International Prostatic Symptom Score
      (I-PSS). Three months after operations patients were submit same tests. Schafer
      nomogram was used for determination of grade of obstruction as well as grade of
      detrusor contractility, and stop flow test is performed to calculate maximal
      estimated flow (Qmaxest). RESULTS: 7 (23, 5%) patients were out of obstruction
      before the operation coupled with detrusor under activity. Postoperatively group
      symptoms reduction, reduction of post void residual (PVR) urine and increase of
      Qmax was noticed. Incidence of detrusor hyperactivity is reduced. As a measure of
      absolute postoperative success for the individual patient, I-PSS <7 with Qmax >15
      ml/sec is taken. By this way, urodynamic measurement have shown sensitivity of
      75%, specificity of 91%, PPV of 75% and post-test probability of 78% for
      prediction of excellent postoperative outcome for the patients with strong
      detrusor who were in the obstruction preoperatively, while stop-flow test with
      Qmaxest >35ml/sec showed lower predictive value of postoperative success
      (sensitivity of 89%, specificity of 62%, PPV of 50% and post-test probability of
      50%). CONCLUSION: Preoperatively obstructed patients with preserved detrusor
      contraction according to Schafer nomogram will experience much better outcome,
      while stop-flow test is not powerful indicator of postoperative favorable
      outcome.

PMID- 15997678
TI  - [Predictors of AV fistula adequacy in haemodialysed patients].
AB  - INTRODUCTION: Vascular access failure remains a significant problem in
      haemodialysis. Complications of dialysis access represent major cause of
      morbidity in dialysis patients. The aim of our study was to correlate the AV
      fistula adequacy with clinical and demographic factors. MATERIAL AND METHODS: The
      survey encompassed 40 patients followed up in one-year period. AV-fistula
      adequacy was graded if the blood flow rate was higher or equal to 300 ml/ min. AV
      fistula adequacy was correlated with clinical and demographic factors. Following
      data were gathered: age, gender, diabetic status, body mass index (BMI), serum
      parathyroid hormone (PTH), and serum albumin. RESULTS: The study included 40
      patients (25 males and 15 females), average age of 46.3 +/- 12.65 years and
      haemodialysis duration of 3.16 +/- 2.39 years. 40% of AV-fistulas were created in
      patients older then 65 years. Diabetes was present in 30% of patients. 45% of
      patients were overweighed (BMI > or = 27 kg/m2). The mean concentration of intact
      PTH was 418.867 +/- 320.44. Serum PTH was higher then 500 pg/mol in 35% of
      patients. The mean serum albumin concentration was 40.129 +/- 3.509 g/l. AV
      fistula adequacy was lower in older patients (age > or = 65) then in younger
      patients (age < 65). The difference in AV fistula adequacy between patients with
      BMI > or = 27 kg/m2 was statistically highly significant (p < 0.001). Lower
      overweighed patients had better AV-fistula adequacy. Serum albumin, as well as
      the PTH level did not influence AV-fistula adequacy, while age and BMI
      significantly correlated with AV-fistula adequacy. CONCLUSION: Predictors of AV
      fistula malfunction in our dialysis population were age, diabetes and overweight,
      while other clinical and demographical factors did not influence AV-fistula
      adequacy.

PMID- 15997679
TI  - [Possibilities of unipolar hip hemiarthroplasty after femoral neck fracture].
AB  - Due to osteoporosis and incoordination, elderly people are prone to hip
      fractures. Hip endoprosthesis is the most rational treatment of such injuries at
      persons older that 65 years of age. Aim of our work was to analyze long term
      clinical result at the elderly patients with implanted unipolar partial hip
      endoprothesis after femoral neck fracture. Inclusion criteria were implantation
      of unipolar partial hip endoprothesis as the first operative procedure and
      absence of changes visible an X-ray. Our follow up was at least 18 months and all
      patients were treated between January 1996 and June 2001 at the Clinic for
      Orthopedics and Traumatology in Sarajevo according to department protocol. We
      used Harris hip score (HHS) for clinical evaluation. From basic group of 131
      patients, in retroprospective prospective research with average follow up period
      of 40 months, 32 patients were clinically examined, others passed away or were
      not reachable. Life expectancy in basic group was 3.5 years and average HHS in
      examined group was 72,06 points. Our study showed that unipolar partial hip
      endoprothesis implanted after femoral neck fracture achieves long term fair
      clinical result. Main factor on a patient's recovery is not type of implanted hip
      endoprothesis, but general health condition before injury, motivation and early
      postoperative mobilization.

PMID- 15997680
TI  - [The frequency of female genital cancer at Gynecological Department in Cantonal
      Hospital Zenica--before, during and postwar time in Bosnia-Herzegovina].
AB  - This targeted, retrospective, descriptive, controlled and open study comprises
      the last decade of the 20th Century and all histologically verified malign
      tumours at the Cantonal Hospital Zenica. By analysing pathohistological findings,
      865 malign genital tumours were found; where the most numerous were cervical
      maligns (70.06%), then corporal (17.34%), ovarian (10.40%), vulvae 1.16%, vaginal
      0.69% and tubal 0.35%. Malign frequency curve shows continual decrease till the
      war year 1993 and continual increase from that period till 2000. The most
      frequent type of malign tumour is carcinoma with the frequency of over 98%
      (70.06% carcinoma planocellulare, 27.86 adenocarcinoma), while recently
      literature shows a bit over 90% of frequency. More than 3/4 of all malign genital
      tumours were discovered in nullity and first clinical stages. Results show that
      approximately 9/10 of all malign processes in female genital tract occurred at
      uterus. The most frequent are malign tumours that are histologically best
      differentiated, while the least frequent are those that are insufficiently
      differentiated. Malign diseases, due to cervical cancer, which encumbers more
      than half of the cases, mostly afflict age group of 35-49, while the age group 50
      64 is mostly afflicted by corporal and ovarian malign tumours. Comparing the year
      1991 with 1993, 1995, 1997 and 1999, no statistically significant difference was
      found occurrence of menarha at women who have cervical, corporal and ovarian
      malign tumours (p>0.05).

PMID- 15997681
TI  - [Cerebral palsy and epilepsy in children].
AB  - Cerebral palsy is a pathological state characterized primarily with the damage to
      the motoric functioning which can be accompanied by the other disorders such as:
      problems with sight and hearing, intellectual deficit, emotional problems,
      conduct disorders, speech disorders, epileptic seizures etc. Martin Bax defines
      this entity as a disorder of movements and postural balance due to defect or
      damage of the young brain (Gavrankapetanovic I. at all., 2001). Study of the
      influence of prenatal ethiological factors on learning difficulties of children
      and adolescents with cerebral palsy in Canton Sarajevo is cohort,
      epidemiologicaly based and retrospectively prospective. In this study a
      Structural interview for the parents of children and adolescents with cerebral
      palsy was used. Sample was consisted of 80 respondents, children and adolescents
      with cerebral palsy of Canton Sarajevo, age from 6 up to 20 years, mean age was
      13.94 years, 47 male 858.75%) and 33 (41.25%) female. In the group of respondents
      with illnesses during pregnancy 16 (53.3%) have epilepsy, and 14 (46.7%) does
      not. In the group withaut illnesses during pregnancy 17 (34%) have epilepsy, and
      33 (66%) does not. Risk ration is 1.59 which means that these respondents whose
      mothers had illnesses during pregnancy have 1.6 times larger probability of
      developing epilepsy.

PMID- 15997682
TI  - [Multiple sclerosis therapy].
AB  - Although still with the unclear etiology, multiple sclerosis (MS) is, according
      to the majority of researchers, autoimmune disease which affects people with the
      genetic predisposition. This is illness of the white mass of the brain and spinal
      cord which is causing damage to the myelin, but also to the degeneration of the
      axons, with the accompanying inflammatory reaction. Clinical course of the
      illness is characterized by wide distribution in time and space. It is more
      common among women than man (in some cases that ratio could be (3:1), among white
      than black, and it shows different geographical distribution. It is most frequent
      at the age from 20 to 40 years, but it is not uncommon in younger and older ages.
      Related to its still unknown ethiology the therapy in best case is
      imunomodulational or immunosuppressive, but in the majority of cases
      symptolmatological. After all of this question occurred: WHEN AND WHICH THERAPY
      WE SHOULD USE FOR THE PATIENTS?

PMID- 15997683
TI  - [Modern approach to treatment of juvenile rheumatoid arthritis].
AB  - PURPOSE: Juvenile rheumatoid arthritis (JRA) is the most common form of arthritis
      in paediatric population. The aim of this study is to evaluate patients (pts)
      with JRA in correlation to age, sex, type of illness as well as treatment
      algorhytm and its efficacy. WORK METHOD: During period time from 1.1.2002. till
      31.12.2001. patients with JRA hospitalised at Paediatric Clinic of the Clinical
      Centre of University of Sarajevo were retrospectively studied. The soruce of
      research was histories of illness, clinical examinations and clinical findings
      during follow-up period. WORK RESULTS: according to our data girls were more
      often affected with JRA-23 patients (66%) age 2 to 6 years. The most frequent
      type of illness was monoarticular in 48.5%, polyarticular 34.2% and systemic in
      14.3%. All pts were treated with first line therapy: nonsteroid anti-inflammatory
      agents combined with physio therapy which had satisfactory outcome, so 80%
      patients entered the remission zone of illness. Patients with systemic (14.3%)
      and polyarticular form with complications, received steroid therapy. One patient
      with systemic form was treated withmethotrexat. Duration of pts stay at Clinic
      differ from illness, 35% were cured and 5% non-cured patients. DISSCUSION:
      Treatment of JRA is a combination of medications, physio therapy and psycho
      therapy. The goals of treatment are to relive pain and inflammation, slow down or
      to prevent the destruction of joints and to restore use and function of affected
      joints in order to promote optimal child's growth and development,
      physicalactivity, social and emotional development. CONCLUSION: Treatment with
      nonsteroid antireumatics in combination with physio therapy proved very
      successful in patents with JRA. Multidisciplinary approach is mandatory to
      achieve primary goal: to cure illness. It is necessary to start therapeutic
      algorhytm as early as possible in best patient's interest.

PMID- 15997684
TI  - Dysthanasia: the (il)legitimacy of artificially posponed death.
AB  - The concept of "dysthanasia" is still partially known in the world academic
      community. The concept is opposite to the concept of "euthanasia", incomparably
      more often mentioned, but without doubt much less often practiced in health-care
      institutions, especially in intensive care units. The objective of this article
      is to expound fundamental theoretical and practical aspects of dysthanasia, as
      well as to encourage discussion about this actual topic. The article discusses
      the position of dysthanasia within the objectives of contemporary medicine, as
      well as according to the definition of health by the WHO the definition of
      illness by the Hastings Center and the Recommendation No. 1418 of the Council of
      Europe Parliamentary Assembly. It concludes with comments on certain examples of
      possible dysthanasia from the world history and two actual examples from our
      clinical practice.

PMID- 15997685
TI  - [Treatment of rupture of the infrarenal aneurysm of the abdominal aorta].
AB  - One of the 15 most common cause of death in USA is rupture of the aneurism of the
      abdominal aorta. In 8-10% cases patients have no previous symptoms of aneurysm of
      the abdominal aorta, and they are coming to thr hospital with clinical picture of
      rupture This paperwork presents one such case. After assuming the data of basic
      lab. findings, clinical finding, and diagnostic procedures, an urgent operation
      was indicated. A resection of aneurismaticly changed infrarenal portion of
      abdominal aorta and its reconstruction with synthetic graft was done. In
      postoperative course we noticed cardiac decompensation followed by acute
      ischaemic attac of the left lower limb. It was solved by urgent disobliterative
      procedure--embolectomy in local anestesion. Patient was discharged after 21 day
      in good general condition.

PMID- 15997686
TI  - [Rupture of interventricular septum as consequence of diaphragmatic heart
      infarct].
AB  - Patient, with massive heart attack of the hart's lower wall which happened six
      months ago, and consequent rupture of the ventricular septum, 1.2 cm of size,
      next to the left to right shunt, and development of aneurisms at the place of
      heart attack (4.2 cm x 2.9 cm), is admitted in our Clinic. Weakening signs of the
      right heart are present with retention of the liquid, edemas and ascites. After a
      long preoperative preparation graft on CX is being performed, reconstruction of
      aneurisms of the left verticle, and VSD being reconstructed with Dacron's patch.
      Postoperative flow is extended with occurrence of profusely diarrhea and
      existence of a smaller pericardial effusion, but status of the patient is
      improving, and he is being dismissed home in a satisfactory general condition.

PMID- 15997687
TI  - [Foeto-foetal conflict of interests in multiple pregnancies with severe
      discordant growth; ethical dilemmas].
AB  - Two pregnant women, 19 and 26 years old, presented at the beginning of the third
      trimester with one growth-retarded foetus in a multiple pregnancy. Both cases
      were managed conservatively. In the first woman, one foetus died at 30 weeks of
      gestation, after the mother developed pre-eclampsia. After the death of the
      impaired foetus pre-eclampsia resolved and the second child was born healthy at
      36 weeks of gestation. The second woman had triplets with one severely growth
      retarded foetus. This foetus died at 3I weeks of gestation. At 33 & 317 weeks,
      caesarean section was performed on both maternal and foetal indications. Two
      healthy premature neonates were born. In multiple pregnancy with discordant
      growth, the interests of the foetuses may be in opposition, which creates an
      ethical dilemma. This may be resolved by carefully addressing the interests of
      all those involved and keeping in mind the prognosis, duration of pregnancy and
      the best interests of the healthy foetus, which should not be harmed by
      intervention. Therefore, active intervention is not always the best option; the
      least harm it does is increasing the risk ofpreterm birth.

PMID- 15997688
TI  - [Patients with lung emboli and hemodynamic stability: insufficient evidence for
      routine thrombolysis].
AB  - Pulmonary embolism (PE) is a common disorder requiring prompt anticoagulant
      treatment. As spiral CT has become the first-line test for PE diagnosis,
      physicians will likely be increasingly confronted with patients displaying large
      centrally located pulmonary emboli. Evidence from literature supporting the use
      ofthrombolytic drugs in patients with PE is sparse, since only one small trial
      has demonstrated that these drugs can reduce short-term mortality in patients
      with emboli and shock. Patients with PE can present without massive arterial
      hypotension but with signs of right ventricular dysfunction on echocardiography
      or CT. One recent randomised trial evaluated whether these haemodynamically
      stable patients would benefit from thrombolytic therapy. However, no definitive
      conclusions can be drawn from this study. Potentially, other prognostic markers
      including brain type natriuretic peptide may be better predictors of suitable
      candidates for thrombolytic therapy. It is concluded that based on current
      knowledge, patients with PE who presentwithout arterial hypotension should not
      routinely be treated with thrombolytic drugs, irrespective of whether they
      display central emboli on CT or not.

PMID- 15997689
TI  - [Temozolomide in patients with a glioblastoma multiforme: new developments].
AB  - There are new scientific data concerning the treatment of patients with
      glioblastoma multiforme with concomitant and adjuvant temozolomide following
      surgery and radiotherapy. Patients have an improved survival rate, especially if
      they also have a methylated promoter of the methylguanine-DNA-methyltransferase
      (MGMT) gene. It is advisable to consider treating young patients with primary
      glioblastoma multiforme who are in good condition with concomitant and adjuvant
      temozolomide. Efficacy of temozolomide in recurrent glioblastoma multiforme is
      limited.

PMID- 15997690
TI  - [The oligodendroglioma: the value of histologic and genetic diagnosis in
      predicting sensitivity to chemotherapy].
AB  - During the past decade, there has been increasing interest in oligodendrogliomas
      because of their sensitivity to chemotherapy. However, making the
      histopathological diagnosis suffers from subjectivity in many cases.
      Oligodendrogliomas possess a 'genetic signature' that correlates well with the
      sensitivity of the tumour to chemotherapy, namely, the loss of parts of
      chromosome arms 1p and 19q. Hence, in cases of oligodendroglial tumors with
      disputable histology, additional genotyping to reveal losses on 1p/19q has become
      a valuable addition for making decisions for treatment.

PMID- 15997691
TI  - [Guideline "Dyspepsia"].
AB  - For the management of patients with dyspepsia a multidisciplinary working party
      has made recommendations, i.e. about indications for prompt endoscopy, the
      management of dyspeptic complaints of recent onset, the application of diagnostic
      tests and treatment of recurrent dyspepsia and the indications for long term use
      of acid suppressants. Endoscopy is indicated in every patient with alarm
      symptoms, i.e. blood loss, dysphagia, weight loss or anemia in combination with
      dyspepsia. Age alone is not a decisive factor in this. Given the good prognosis
      of recent onset dyspepsia, the application of diagnostic tests is generally not
      required. Treatment should be restricted to antacids or H2 receptor antagonists.
      Only in case of persistent or recurring complaints, diagnostic tests or another
      treatment (Helitobacter pylori diagnostic tests, empirical treatment or
      endoscopy) should be considered. Testing for H. pylori is especially effective in
      patients at risk for peptic ulcer disease: those with recurrent complaints, and
      those with a history of peptic ulcer, without typical reflux symptoms or those
      with a history ofpeptic ulcer. Short term empirical treatment with a proton pump
      inhibitor is especially effective in patients with typical reflux symptoms.
      Endoscopy is the only way to rule out malignancy, and should be used to solve
      serious diagnostic uncertainty in patient or physician. The only indication for
      continuous proton pump inhibitor treatment is severe oesophagitis. All other
      patients with less severe reflux disease should preferably be treated on either
      on demand or intermittent basis. Long term proton pump inhibitor treatment is not
      indicated for patients with peptic ulcer disease or functional dyspepsia.

PMID- 15997692
TI  - [Favourable result for temozolomide in recurrent high-grade glioma].
AB  - OBJECTIVE: To describe the results of the treatment of recurrent glioma with
      temozolomide. DESIGN: Retrospective. METHOD: This study evaluated 77 patients
      with a recurrent high-grade glioma who from August 1997-December 2003 were
      treated with temozolomide (150-200 mg/m2/day for 5 days per 28-day cycle)
      following surgery and radiotherapy at the Daniel den Hoed Oncology Centre of the
      Erasmus MC, Rotterdam, the Netherlands. The patients were divided into 4 groups
      depending on histology and chemotherapy history. RESULTS: 15 patients received
      temozolomide for a recurrent anaplastic oligodendroglioma or mixed oligo
      astrocytoma. The response in this group was 80% and after 12 months in 47% of the
      patients there was no disease progression. 35 patients underwent second-line
      chemotherapy with temozolomide after earlier chemotherapy with procarbazine,
      lomustine and vincristine for recurrent anaplastic oligodendroglioma or mixed
      oligo-astrocytoma. Response was 26% and after 12 months in 15% of patients there
      was still no disease progression. 14 patients were treated with temozolomide for
      a recurrent anaplastic astrocytoma with a response of 35% and after 12 months in
      8% of these patients there was no disease progression. Of the 13 patients with a
      recurrent glioblastoma who were treated with temozolomide 16% responded and after
      6 and 12 months 21% were still free from progression. Temozolomide was well
      tolerated: 2 patients had to stop because of probable side effects. CONCLUSION.
      Temozolomide has an acceptable safety profile and may be regarded as the
      preferred treatment for recurrent anaplastic gliomas after radiotherapy. There is
      only a limited role for temozolomide in the treatment of recurrent glioblastoma.

PMID- 15997693
TI  - [Therapeutic dilemmas in patients with a centrally-located pulmonary embolism
      confirmed by spiral CT-scan but with no cardiogenic shock].
AB  - 3 patients, 2 women aged 64 and 44 and 1 man aged 67, had severe dyspnoea and a
      large centrally-located pulmonary embolism (PE) without any accompanying arterial
      hypotension. They were all given conventional anticoagulation therapy, although
      thrombolytic therapy was also considered. The women recovered but the man
      eventually died of a second massive embolism. PE is a disease with a potentially
      high mortality. Patients with cardiogenic shock due to PE are candidates for
      thrombolytic therapy. A subset of patients with right-ventricular dysfunction
      (submassive PE) also have a poorer prognosis despite the absence ofarterial
      hypotension or shock. Spiral CT-scan is becoming the first-line imaging test of
      preference in patients with suspected PE. Spiral CT enables the accurate
      visualization ofthrombi. The value of risk management using cardial biomarkers,
      spiral CT and echocardiography is not yet clear. There is no evidence that
      thrombolytic therapy is beneficial in patients with acute PE and right
      ventricular dysfunction without overt shock.

PMID- 15997694
TI  - [Epileptic seizures during childbirth in a patient with idiopathic generalised
      epilepsy].
AB  - During her first pregnancy, a 37-year-old woman with idiopathic generalised
      epilepsy that was adequately controlled with lamotrigine experienced a series of
      epileptic seizures following an elective caesarean section. The attacks were
      terminated with diazepam. The following day, she developed EEG-confirmed status
      epilepticus, for which midazolam was administered intravenously. No further
      attacks were observed and the patient was later discharged in good condition with
      a healthy newborn son. She remained on lamotrigine therapy. At the end of her
      second pregnancy, the patient again experienced tonic-clonic seizures. The dosage
      of lamotrigine was increased and the patient received clonazepam intravenously,
      but a new seizure quickly occurred. Following an emergency caesarean section with
      midazolam treatment, a healthy daughter was born. No further attacks were
      observed. This case history illustrates the occurrence of adult idiopathic
      generalised epilepsy and highlights the problems that can arise late in pregnancy
      and during childbirth.

PMID- 15997695
TI  - [The Dutch law on artificial-insemination donor data: content and consequences].
AB  - In 2004, a law was introduced in the Netherlands that gives children conceived by
      artificial insemination with donor semen (AID), oocytes or embryos the right to
      learn the identity of the donor when they are 16. The permanently anonymous semen
      donor will now be replaced by donors that are anonymous at the time of
      insemination, but traceable later. During the period preceding and immediately
      following the enactment of the law, the number of semen donors and semen banks
      dropped drastically and there was a change in the type of donor. The law,
      furthermore, creates several new moral and psychological dilemmas for both
      parents and AID-offspring. For parents, for example: should I tell my child that
      he was conceived by AID, knowing that he may become acquainted with the donor,
      with all the consequences that may entail? And for AID-offspring, if they have
      been told that they were conceived by AID: do I really wish to meet the donor? It
      must still be shown whether AID-offspring will feel a need for contact with the
      donor, and whether such contact is satisfying.

PMID- 15997696
TI  - [Measuring the length of newborn infants].

PMID- 15997697
TI  - [Timing and choice of intervention in necrotising pancreatitis].

PMID- 15997698
TI  - [Sexual harassment of medical students during their period of work placement].

PMID- 15997699
TI  - [A malignant tumour in the breast is not always primary breast cancer].

PMID- 15997700
TI  - A catabolic gene cluster for anaerobic benzoate degradation in methanotrophic
      microbial Black Sea mats.
AB  - A microbial mat from the Black Sea shelf was analyzed by a metagenomic approach.
      While the habitat and its microbial community are characterized by anaerobic
      methane oxidation, a 79 kb contiguous DNA sequence obtained from the same mat
      provided first evidence for the concomitant presence of the capacity for
      anaerobic benzoate degradation. Benzoyl-CoA is one central intermediate of
      anaerobic aromatic degradation, among others. Within a stretch of 31 kb, all
      genes required for the complete pathway of anaerobic benzoate degradation
      (catabolic island) were identified, including the four subunits of the key enzyme
      benzoyl-CoA reductase (bcrCBAD), which catalyzes the ATP-driven 2-electron
      reduction of the aromatic ring. Genes for a ketoacid:acceptor oxidoreductase
      (korABC) and a ferredoxin (fdx), which are required for generation of a suitable
      electron donor, were also detected. The majority of the identified catabolic gene
      products are most similar to their respective orthologs from the denitrifying
      freshwater bacterium Azoarcus evansii, and the genes are also similarly
      organized. Due to the lack of established markers, the phylogenetic affiliation
      of the source organism remains unclear. The presented findings indicate that the
      metabolic diversity of the Black Sea mat is wider than currently known and that
      probably other bacteria than those of the methane-oxidizing consortia contribute
      to aromatic degradation in this anoxic habitat.

PMID- 15997701
TI  - Phenylobacterium falsum sp. nov., an Alphaproteobacterium isolated from a
      nonsaline alkaline groundwater, and emended description of the genus
      Phenylobacterium.
AB  - A Gram-negative bacterium designated AC-49T was isolated from an alkaline
      groundwater with a pH 11.4. This organism formed rod-shaped cells, was strictly
      aerobic, catalase and oxidase positive, with an optimum growth temperature of 35
      degrees C and an optimum pH value of 8.0. Strain AC-49T assimilated primarily
      amino acids and some Krebs cycle metabolites, did not use sugars for growth. The
      organism did not grow on L-phenylalanine or antipyrin. The G+ C content of DNA
      was 66.9 mol%. The phylogenetic analyses based on the 16S rRNA sequencing showed
      that the closest relatives of strain AC-49T were Phenylobacterium lituiforme and
      Phenylobacterium immobile, indicating that the organism is a member of the order
      Caulobacterales of the Alphaproteobacteria. Based on the phylogenetic analyses
      and distinct phenotypic characteristics, we are of the opinion that strain AC
      49T, represents a novel species of the genus Phenylobacterium for which we
      propose the name Phenylobacterium falsum sp. nov.

PMID- 15997702
TI  - Methylophilus quaylei sp. nov., a new aerobic obligately methylotrophic
      bacterium.
AB  - A new obligately methylotrophic bacterium (strain MTT) with the ribulose
      monophosphate pathway of carbon assimilation is described. The isolate, utilizing
      only methanol, is an aerobic, Gram-negative, asporogenous, non-motile short rod
      multiplying by binary fission. Its cellular fatty acids profile consists
      primarily of straight-chain saturated C16:0 and unsaturated C16:l acids. The
      major ubiquinone is Q-8. The dominant phospholipids are phosphatidylethanolamine
      and phosphatidylglycerol. Diphosphatidylglycerol (cardiolipin) is absent. Optimal
      growth conditions are 25-29 degree C, pH 6.5 - 7.5, 0.5% CH3OH and 0.05% NaCl.
      Strain MTT lacks alpha-ketoglutarate dehydrogenase, the glyoxylate shunt enzymes,
      and glutamate dehydrogenase. Ammonium is assimilated by the operation of the
      glutamate cycle enzymes: glutamine synthetase and glutamate synthase. An
      exopolysaccharide consisting of rhamnose, glucose and galactose is formed under
      nitrogen limitation. The G + C content of the DNA is 54.0 mol%. Based on 16S rDNA
      sequence analysis and DNA-DNA relatedness (29-34%) with type strains of the genus
      Methylophilus, the novel isolate was classified as a new species of this genus
      and named Methylophilus quaylei MTT (VKM B-2338T, DSMZ, etc.).

PMID- 15997703
TI  - Flavobacterium frigidimaris sp. nov., isolated from Antarctic seawater.
AB  - We described the polyphasic characterization of the psychrotolerant isolated from
      Antarctic seawater. The strain was closely related to Flavobacterium hydatis, F.
      pectinovorum, and F. saccharophilum on the basis of the 16S rDNA sequence
      analysis. However, DNA-DNA hybridization experiments showed that the DNA
      similarities between strain KUC-1T and the reference strains of Flavobacterium
      were less than 30%. Therefore, we can definite a new species of Flavobacterium
      phylogenetically, and strain KUC-1T can be considered to be a new species of
      Flavobacterium. i.e. F. frigidimaris (KUC-1T: JCM 12218T and DSM 15937T; mol% G+C
      of DNA of the type strain is 34.5 mol%). Useful phenotypical features for
      discrimination of F. frigidimaris from other Flavobacterium species, such as a
      resistance to NaCl, optimum growth temperature, and cellular fatty acid
      composition, were also determined.

PMID- 15997704
TI  - Alkanindiges hongkongensis sp. nov. A novel Alkanindiges species isolated from a
      patient with parotid abscess.
AB  - A bacterium was isolated from the abscess pus of a 72-year-old patient with
      Warthin's tumor and parotid abscess. The cells were aerobic, non-motile, Gram
      negative but difficult to be destained, non-sporulating, coccobacillus. The
      bacterium grew poorly on sheep blood agar and MacConkey agar as non-hemolytic
      colonies of 0.5 mm in diameter after 24h of incubation at 37 degrees C in ambient
      air. Growth was enhanced by Tween 80. It produces catalase but not cytochrome
      oxidase. Sequencing of the cloned 16S rRNA PCR products of the bacterium revealed
      three different 16S rRNA gene sequences, with 12 - 31 bp differences among them.
      Phylogenetic analysis showed that the bacterium is closely related to
      Alkanindiges illinoisensis, with 5.0 - 5.9% differences between the 16S rRNA gene
      sequence of the bacterium and that of A. illinoisensis. Tryptophan auxotrophic
      strain of Acinetobacter trpE27 transformed with DNA extracted from the bacterium
      was unable to grow on tryptophan deficient medium, indicating that the bacterium
      was not a strain of Acinetobacter. The G+C content of the bacterium (mean +/-SD)
      was 46.9+4.3%. A new species, Alkanindiges hongkongensis sp. nov., is proposed,
      for which HKU9T is the type strain. Isolates with "small colonies" that are
      apparently Acinetobacter-like species should be carefully identified. Growth
      enhancement with aliphatic hydrocarbons should be looked for and 16S rRNA gene
      sequencing performed in order to find more potential cases of Alkanindiges
      infections, as well as to define the epidemiology, clinical spectrum, and outcome
      of infections associated with this genus.

PMID- 15997705
TI  - Bacillus nematocida sp. nov., a novel bacterial strain with nematotoxic activity
      isolated from soil in Yunnan, China.
AB  - An endospore-forming bacterium, designated strain B-16T, was isolated from a
      forest soil sample in Yunnan, China. The isolate presented remarkable nematotoxic
      activity against nematode Panagrellus redivivus. The organism was strictly
      aerobic, motile, spore forming and rod shaped, catalase- and oxidase-positive.
      The predominant isoprenoid quinone was menaquinone 7 (MK-7). The major cellular
      fatty acid profiles were anteiso-C15:0 (48.67%), iso-C15:0 (13.45%), C16:0
      (9.06%) and anteiso-Cl7:0 (8.29%). The DNA G+C content was 46%. Phylogenetic
      analyses based on 16S rDNA sequence revealed that isolate belongs to the genus
      Bacillus. Strain B-16T exhibited high 16S rDNA similarity with its closest
      neighbors Bacillus vallismortis (99.79%), B. subtilis (99.43%), B. atrophaeus
      (99.43%), B. amyloliquefaciens (99.36%), B. licheniformis (98.0%) and less than
      97.0% with all the other relative type strains in the genus Bacillus. The
      phenotypic and genotypic characteristics and DNA-DNA relatedness data indicate
      that strain B-16T should be distinguished from all the relative species of genus
      Bacillus. Therefore, on the basis of the polyphasic taxonomic data presented, a
      new species of the genus Bacillus, B. nematocida, with the type strain B-16T ( =
      CGMCC 1128T) is proposed. The GenBank accession number for the sequence reported
      in this paper is AY820954.

PMID- 15997706
TI  - Eight new species of the genus Micromonospora, Micromonospora citrea sp. nov.,
      Micromonospora echinaurantiaca sp. nov., Micromonospora echinofusca sp. nov.
      Micromonospora fulviviridis sp. nov., Micromonospora inyonensis sp. nov.,
      Micromonospora peucetia sp. nov., Micromonospora sagamiensis sp. nov., and
      Micromonospora viridifaciens sp. nov.
AB  - A previous phylogenetic study on type strains of the genus Micromonospora and
      Micromonospora species bearing non-validly published names has pointed towards
      the species status of several of latter strains. Subsequent studies on
      morphological, cultural, chemotaxonomic, metabolic, and genomic properties, and
      on whole cell mass spectrometric analyses by matrix adsorbed laser
      desorption/ionization time-of-flight (MALDI-TOF) confirmed the species status,
      leading to the proposal of eight new Micromonospora species: Micromonospora
      citrea sp. nov., type strain DSM 43903T, Micromonospora echinaurantiaca sp. nov.,
      type strain DSM 43904T, Micromonospora echinofusca sp. nov., type strain DSM
      43913T, Micromonospora fulviviridis sp. nov., type strain DSM 43906T,
      Micromonospora inyonensis sp. nov., type strain DSM 46123T, Micromonospora
      peucetia sp. nov., type strain DSM 43363T, Micromonospora sagamiensis sp. nov.,
      type strain DSM 43912T and Micromonospora viridifaciens sp. nov., type strain DSM
      43909T.

PMID- 15997707
TI  - Identification and typing of food-borne Staphylococcus aureus by PCR-based
      techniques.
AB  - The possibility of using PCR for rapid identification of food-borne
      Staphylococcus aureus isolates was evaluated as an alternative to the API-Staph
      system. A total of 158 strains, 15 S. aureus, 12 other staphylococcal species,
      and 131 isolates recovered from 164 food samples were studied. They were
      phenotypically characterized by API-Staph profiles and tested for PCR
      amplification with specific primers directed to thermonuclease (nuc) and
      enterotoxin (sea to see) genes. Disagreement between the PCR results and API
      Staph identification was further assessed by the analysis of randomly amplified
      polymorphic DNA (RAPD) profiles obtained with three universal primers (M13, T3,
      and T7) and 16S rDNA sequencing. Forty out of 131 isolates (31%) tested positive
      for PCR enterotoxin. Of these, 14 (11%) were positive for sea, 22 (17%) for sec,
      one (0.8%) for sed, and three (2.2%) for sea and sec. No amplification
      corresponding to seb nor see was obtained. Cluster analysis based on RAPD
      profiles revealed that most of the sec positive food isolates grouped together in
      three clusters. Cluster analysis combining the three RAPD fingerprints (M 13, T3,
      and T7), PCR-enterotoxin genotype and API-Staph profiles, grouped the nuc PCR
      positive isolates together with S. aureus reference strains and the nuc PCR
      negative isolates with reference strains of other staphylococcal species. The
      only nuc PCR positive food isolate that remained unclustered was a sed positive
      strain identified by 16S rDNA sequence as S. simulans. The high concordance
      between S. aureus and nuc PCR positive strains (99%) corroborates the specificity
      of the primers used and the suitability of nuc PCR for rapid identification of S.
      aureus in routine food analysis.

PMID- 15997708
TI  - A comparative evaluation of phenotypic and molecular methods in the
      identification of members of the Staphylococcus sciuri group.
AB  - Members of the Staphylococcus sciuri group (S. sciuri, S. lentus, and S.
      vitulinus) are coagulase-negative, novobiocin-resistant staphylococci that could
      be distinguished from other staphylococci on the basis of positive oxidase
      activity. In the present study, a scheme based on conventional methods and
      utilization of various carbohydrates was evaluated for the identification of
      oxidase-positive staphylococci, and validated using two molecular techniques. Of
      the 173 oxidase-positive staphylococcal tested strains, 161 were identified as S.
      sciuri, 9 as S. lentus, 2 as S. vitulinus, and one as S. fleurettii by our
      scheme. The level of agreement with tRNA intergenic length polymorphism analysis
      (tDNA-PCR) was high (97.5-100% correlation). The accuracy and ease of use of this
      protocol suggest that it may be useful and valuable in microbiological
      laboratories for the identification of members of this group.

PMID- 15997709
TI  - Isolation of tannin-degrading bacteria isolated from feces of the Japanese large
      wood mouse, Apodemus speciosus, feeding on tannin-rich acorns.
AB  - Bacteria with tannase activity were isolated from the feces of the Japanese large
      wood mouse, Apodemus speciosus. They were largely classified into two groups:
      Gram-positive cocci and Gram-positive bacilli. Genotypic analysis using a species
      specific PCR assay as well as biochemical tests identified all cocci as
      Streptococcus gallolyticus. A PCR assay targeting a genus-specific sequence in
      the 16S/23S rDNA spacer region and additional 16S rDNA sequencing indicated that
      the bacilli belong to the genus Lactobacillus, with L. animalis and L. murinus
      being closely related taxa. Subsequent estimation of guanine-plus-cytosine
      content, amplified ribosomal DNA restriction analysis, and DNA/ DNA hybridization
      assay confirmed that the bacilli are homologous to each other but different from
      L. animalis or L. murinus. Consequently, a novel species of the genus
      Lactobacillus may be proposed. To date, this study is the first to report on the
      isolation of tannase-positive bacteria from the feces of a rodent species. These
      bacteria may play an essential role for the host organism in digesting tannin
      rich acorns available in their natural habitats, thereby endowing them with a
      greater ecological advantage.

PMID- 15997710
TI  - Molecular characterisation of Xanthomonas strains isolated from aroids in
      Mauritius.
AB  - Mauritius is one of the largest world producers of Anthurium cut flowers but
      outbreaks of bacterial blight have never been reported on the island. This work
      was about the characterisation and identification of bacterial strains isolated
      from Anthurium andreanum, Dieffenbachia maculata and Aglaonema simplex in
      Mauritius. Fifteen strains, that showed the morphological properties of
      Xanthomonas on conventional media, were tested on two semi-selective media
      (Esculin-trehalose and cellobiose-starch). ELISA tests using a panel of
      monoclonal antibodies were carried out and three out of 15 strains reacted with a
      Xanthomonas-specific monoclonal antibody (MAb XII). Analysis using four sets of
      ribosomal primers revealed that the same three Mauritius strains shared conserved
      PCR products with reference xanthomonads including virulent strains of
      Xanthomonas axonopodis pv. dieffenbachiae (Xad). BIOLOG tests and the Sherlock
      Microbial Identification system (MIDI) identified these three new strains at the
      species level as X. axonopodis. The complementary tests that were carried out
      clearly confirmed that the three strains are xanthomonads and, moreover, a DNA
      probe which showed specificity to Xad strains suggested that the three Mauritius
      strains are non-virulent forms of the pathogen causing Anthurium blight.

PMID- 15997711
TI  - [Interprofessional collaboration between medicine and nursing].

PMID- 15997712
TI  - [The efficacy of non-pharmacological interventions in the management of pain in
      preterm and term neonates. A systematic literature review].
AB  - Many diagnostic and therapeutic procedures performed in the neonatal intensive
      care unit are painful for the preterm or term infant. Pain is therefore a central
      issue in neonatal intensive care nursing. As significant side effects are
      associated with analgesics, non-pharmacological methods of pain prevention and
      relief are being favoured over pharmacological therapy. This development is very
      important for the nursing profession since non-pharmacological interventions are
      determined and carried out without an order from a physician. This review of the
      current literature investigates the efficacy of non-pharmacological nursing
      interventions in the management of pain in the neonatal intensive care unit.
      Despite certain methodological problems with some of the studies included in this
      review, the trend favours non-pharmacological interventions. Modulation of
      arousal and excitability during and after a painful stimulus as well as an effect
      on physiological and behavioural parameters have been described following non
      pharmacological interventions. The studies reviewed suggest that neonates show
      fewer signs of pain and stress after non-pharmacological interventions for
      prevention and relief of pain.

PMID- 15997713
TI  - ["Quality of life means acting independently". How do COPD-patients experience
      non-invasive ventilation? A qualitative study].
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive disorder including
      chronic obstructive bronchitis, emphysema and combinations. The management of
      stable COPD in an advanced stage involves noninvasive mechanical ventilation.
      There is a lack of convincing scientific studies about the influence of
      mechanical ventilation on quality of life. Furthermore the role of nurses taking
      care of people with COPD seems to be unclear. A phenomenological interpretative
      hermeneutical analysis of 15 narrative interviews with non-invasive ventilated
      COPD-patients demonstrates that noninvasive ventilation is associated with
      improvements in patients' autonomy. "To achieve independence" is described as the
      central theme of this study and highlights the benefit of independency on
      patients' quality of life. Other results describe the experiences "To experience
      breathing", "To seize one's possibilities", "To participate in life", "To have to
      live with COPD". The results also show that activities of nurses in particular
      need to include consulting, teaching and monitoring. There is a need for further
      research to evaluate nursing interventions. This study is a first step in
      knowledge generation and serves as a basis for further quantitative research.

PMID- 15997714
TI  - [Which quality criteria are important for relatives about a nursing home? A
      single case study].
AB  - This single-case study undertakes to determine criteria for quality in nursing
      homes as deemed important by immediate family members of inhabitants. The design
      is an explorative, qualitative design with the aim of generating hypotheses. This
      study consists of two parts: 1. a case study of the selected institution 2.
      qualitative interviews with the family members of inhabitants. In order to
      describe the case study of the institution, documents about the nursing home were
      examined and analysed, observations in the nursing home were made, and experts of
      the nursing home were interviewed. Six close relatives of five inhabitants are
      interviewed. The results of these narrative interviews are analysed using coding
      (Strauss, 1998) in the context of this specific home for care of the elderly.
      Findings reveal that interviewees differentiate between a first set of criteria
      for quality of the institution, a second set of criteria for quality of the care
      and a third set of criteria they view as important for their relative living in
      the institution. The overruling priority is given to the third set of criteria
      among which the subjective well-being of the nursing home inhabitant dominates.
      Even in cases where the institution does not meet the requirements of the family
      member, the subjective well-being of the inhabitant is the main reason for not
      moving her/him to another nursing home.

PMID- 15997715
TI  - [Clinical pathways: a way to integrate a standardized treatment and patient
      orientation?].
AB  - The implementation of Diagnosis Related Groups (DRGs) as the payment system for
      hospital work requires to optimise the processes and the use of resources while
      maintaining the quality of care. To achieve these goals hospitals implement
      clinical pathways. The systematic structure of these pathways was developed in
      the industrial context during the 1950s. This history led to the assumption that
      a process begins and ends in a previously-planned most linear motion. This
      assumption creates various problems. First of all, the conditions of the
      situation and the individual's personal needs are ignored. Both aspects are
      relevant for the quality of care as well as for the calculation of the
      expenditures. Another problem is the disregard of communicative understanding,
      the core of nursing. As a result of these problems, the contradictory goals
      satisfying the rationale and communicative needs conflict. This situation creates
      the risk of the functional-orientated orders of the clinical pathways determining
      the relationship between the nurse and the patient. The next risk is that the
      patient will only be a marginal part of the process. In addition, the nurses may
      loose their caring competence. Despite these arguments, the use of clinical
      pathways can be well supported. For the pathway to be successful, the stipulation
      that remains important is for the system to allow flexibility. To achieve this
      flexibility, one must utilize assessment instruments. The steps of the
      intervention process have to be guided by the results of the assessment along
      with the outcome. The art of professional nursing should successfully combine the
      clinical pathway with the patient's individual needs.

PMID- 15997716
TI  - [Covenant or contract? A reflection on two paradigms of the nursing
      relationship].
AB  - This article contains a critical reflexion about two paradigms upon which nurse
      patient relationships can be based: the traditional covenant, rooting in religion
      and ethics and the business-orientated contract. The motive for this reflexion
      lies in the present economic, scientific and societal context of nursing
      practice, which threatens traditional nursing values. It leads to an inflation of
      the covenant paradigm in favour of the contract paradigm, which implies greater
      efficiency. Following the description of the two paradigms the way they determine
      nursing relationships is being compared. On the basis of this confrontation the
      contract as basis of the nursing relationship is discarded. Finally, questions
      concerning the future positioning of nursing and of nursing science in terms of
      the foundation and of the profile of the nurse-patient relationship are asked.

PMID- 15997718
TI  - [What is your diagnosis? Hyperkalemia].

PMID- 15997717
TI  - [Autoimmune polyendocrine syndrome (APS). Chief symptoms depend on involved
      organs].

PMID- 15997719
TI  - [Errors and complications in internal medicine].
AB  - The "Komplikationenliste" (list of complications) of the association of the heads
      of departments of the Swiss society of internal medicine is a clinical tool for
      the registration and reduction of complications/errors of medical treatment. It
      is the aim to improve patient safety in hospital medicine. By the systematic and
      prospective analysis of interventions and complications in the 26 participating
      medical departments it is possible to collect also rare incidents. All the
      complications and errors are communicated to all the departments of internal
      medicine in Switzerland in order to reduce them. The principle for the reduction
      of such events is the elimination of unsafe actions and conditions and apparently
      harmless errors in daily diagnostic and therapeutic interventions in order to
      avoid potentially serious consequences.

PMID- 15997720
TI  - [Certain or possible lethal medical malpractice: what is to do afterwards?].
AB  - In case of a possible or certain lethal case of medical malpractice the following
      procedure is recommended: 1. Scrutinize every death of a patient during or after
      a medical treatment. Address the following questions: "Did everything proceed
      correctly?", "Could death have been prevented?", "This should not have been
      happened". 2. Report to the head physician, to the hospital management and
      administration in order to coordinate the further procedures. 3. Save all the
      evidence: Perfusions, empty phials, opened drug packages. Leave all catheters,
      tubes, drainages on the body! Leave any technical equipment, for example
      anesthetic machines untouched. Save all prior blood and urine samples taken from
      the patient. Seal medical history and documentations. 4. Order a memory protocol
      of the events by all involved persons. 5. Refrain from clinical autopsy. Forensic
      autopsy, indicated in these circumstances, can only be authorized by the district
      attorney (see point 7). If in doubt, seek counseling from an institute of
      forensic medicine by telephone (if requested: anonymously). 6. Put "non natural
      death" on the death certificate in case of a certain and unclear death in case of
      a possible medical malpractice. 7. Report any possible or certain case of lethal
      medical malpractice to the district attorney (obligation to report). The district
      attorney will authorize a 8. Inform the relatives of the deceased. Apologize,
      show regret and concern but do not address the question of guilt. 9. Inform your
      third party insurance (this does not mean an admission of guilt).

PMID- 15997721
TI  - [Hospital drug safety: medication errors and adverse drug reactions].
AB  - BACKGROUND: Drug related problems (medication errors and adverse drug reactions)
      are frequent and cause increased costs. AIMS: Evaluation of the original articles
      published between 1991-2001 reporting frequencies of medication errors and/or
      METHODS: Medline search with the expressions "medication error", "adverse drug
      reaction", "adverse drug event", "hospital" and completion of the retrieved
      articles by evaluating the references and by checking review articles about this
      subject. RESULTS: Medication errors occur with a frequency of 5-10% of all
      applications, studies retrieved. This variability can be explained by the way the
      frequencies are expressed (per application, per patient days or per
      hospitalization), the reporting system (systematic acquisition vs. spontaneous
      reports) and the wards investigated, but not by the distribution system.
      Application errors are more frequent than prescription errors. Risk factors are
      insufficient education in pharmacology, overworked nursing personnel, non
      computerized transmission of the prescriptions and lacking pharmaceutical support
      on the wards. Adverse drug reactions appear in about 8% of the hospitalized
      patients, also with a high variability among the 20 studies retrieved. This
      variability can be explained by differences between the wards studied and by the
      detection systems used. Risk factors are medication errors, female sex, age > 65
      years, polypharmacy, impaired drug elimination and deviance of risk factors (e.g.
      previous allergic reactions). CONCLUSIONS: Computerizing the whole medication
      process and improving the pharmacological education of physicians and nurses
      could help to reduce medication errors. In addition, the adoption of clinical
      pharmacists on critical wards could also lower the medication error rate. For
      lowering the frequency of adverse drug reactions, medication errors should be
      avoided and the dosage of the drugs should be adapted strictly to the function of
      the eliminating organs. Risk factors such as drug allergies and familiar diseases
      should be screened for and drug therapies adapted accordingly. Severe and/or
      novel adverse drug reactions have to be reported to the regional
      pharmacovigilance centers.

PMID- 15997722
TI  - [Anticonvulsive from calmus root?].

PMID- 15997723
TI  - [Idiopathic pulmonary fibrosis: progress in diagnosis and treatment].

PMID- 15997724
TI  - [Idiopathic pulmonary fibrosis: changes in its concept].

PMID- 15997725
TI  - [Idiopathic pulmonary fibrosis: its classification and diagnosis].

PMID- 15997727
TI  - [Idiopathic pulmonary fibrosis: pathology].

PMID- 15997726
TI  - [Idiopathic pulmonary fibrosis: epidemiology and risk factors].

PMID- 15997728
TI  - [Idiopathic pulmonary fibrosis: imaging diagnosis].

PMID- 15997729
TI  - [Idiopathic pulmonary fibrosis: respiratory function tests].

PMID- 15997730
TI  - [Idiopathic pulmonary fibrosis: serum markers].

PMID- 15997731
TI  - [Idiopathic pulmonary fibrosis: steroids and immunosuppressive agents].

PMID- 15997732
TI  - [Development of new therapeutic modalities for idiopathic pulmonary fibrosis:
      from anti-inflammatory agents to anti-fibrosis agents].

PMID- 15997733
TI  - [Current status and overview of idiopathic pulmonary fibrosis: oxygen inhalation
      therapy and artificial respiration].

PMID- 15997734
TI  - [Current status and an overview of treatment of idiopathic pulmonary fibrosis:
      lung transplantation].

PMID- 15997735
TI  - [Familial pulmonary fibrosis].

PMID- 15997736
TI  - [Chronic hypersensitivity pneumonia].

PMID- 15997737
TI  - [Pulmonary fibrosis caused by ARDS].

PMID- 15997738
TI  - [Pulmonary fibrosis caused by infection].

PMID- 15997739
TI  - [Management of interstitial pneumonia: when should the disease be suspected and
      should specialists be consulted with: discussion].

PMID- 15997740
TI  - [Secondary hypertension due to juxtaglomerular cell tumor].

PMID- 15997741
TI  - [Disseminated gonococcal infection].

PMID- 15997742
TI  - [Infectious endocarditis revealed by the rupture of bacterial cerebral aneurysm
      under the treatment of spondylodicitis].

PMID- 15997743
TI  - [Extramedullary relapse with spinal ataxia in a patient with acute promyelocytic
      leukemia after allogeneic peripheral blood stem cell transplantation].

PMID- 15997744
TI  - [Severe tetanus with diabetic foot ulcers].

PMID- 15997745
TI  - [Chronic inflammation and anemia--hepcidin, an iron metabolizing hormone].

PMID- 15997746
TI  - [Molecular targeting drug designing for polycystic kidney].

PMID- 15997747
TI  - [Forefront of neuro-imaging].

PMID- 15997748
TI  - [Efficacy and problems related to female hormone replacement therapy--based on
      the Women's Health Initiative].

PMID- 15997749
TI  - Decisions and trends in cardiovascular surgery facilities standards.

PMID- 15997750
TI  - Long-term results of endoluminal grafting for descending thoracic aortic
      aneurysms.
AB  - OBJECTIVE: This paper describes the long-term results of endoluminal grafting
      (EG) for the treatment of descending thoracic aortic aneurysms (dTAA). METHODS:
      Until July 2004, EG for dTAA has been applied in 45 cases (male/female, 29/16, 49
      86 years old, mean age 67 years old). Locations included the proximal dTAA in 24
      cases, and middle or distal dTAA in 21 cases. The stent-grafts (SGs) were
      constructed of Gianturco Z-stents covered with woven polyester grafts. RESULTS:
      Deployment of the SGs was successful in 43 of 45 cases (96%) and complete
      thrombosis of the aneurysm was achieved in 39 cases (87%). Six minor endoleaks
      (13%), one migration (2%) and one conversion to surgery (2%) occurred. There was
      no instance of paraplegia nor hospital death. Over a mean 48 month follow-up
      (range 3 to 90), there were three persistent endoleaks (6%), four secondary
      endoleaks (8%), one breakage of wire frame (2%). Four cases were converted to
      open surgery due to secondary endoleak. There were two aneurysmal ruptures at the
      site where EG was not performed. The cumulative survival rate was 95.6 +/- 4.4%
      at 12 months, 85.7 +/- 5.4% at 24 months, and 82.4 +/- 6.1% at 36 and 60 months.
      CONCLUSION: These results demonstrated that EG is safe and effective in selected
      dTAA patients. Improvements in patients selection, surgical techniques and
      equipment will reduce EG related complications and conversion to open repair over
      the course of the evaluation.

PMID- 15997751
TI  - Off-pump resection of a coronary arterial fistula using the Harmonic Scalpel.
AB  - Off-pump surgery was performed in a patient with post-infarction angina
      complicated with aneurysmal coronary-pulmonary arterial fistula. Epicardial
      echocardiography localized the artery feeding the fistula in the myocardium,
      which had not been revealed by visual inspection, palpation, or transesophageal
      echocardiography. The patient underwent off-pump coronary artery bypass grafting
      concomitant with aneurysmectomy. The feeding arteries were dissected easily using
      a Harmonic Scalpel and ligated. The flow in the aneurysm disappeared immediately
      and aneurysmectomy was performed without bleeding.

PMID- 15997752
TI  - Mucinous (colloid) adenocarcinoma.
AB  - We describe a case of primary mucinous (colloid) adenocarcinoma of the lung. The
      patient was a 61-year-old male with a peripheral mass of the left lung.
      Retrospectively, the mass, which showed slow growth later, could be seen in a
      chest X-ray 3 years before surgery. The tumor was filled with a gelatinous
      substance resembling strawberry jelly, macroscopically. Microscopically, it was
      mucin with a small amount of malignant cells (adenocarcinoma). Diagnosis was
      mucinous (colloid) adenocarcinoma, which is a very rare intrapulmonary neoplasm.
      Mucinous (colloid) adenocarcinoma is suspected when a gelatinous substance like
      strawberry jelly is observed intraoperatively in the lung.

PMID- 15997753
TI  - Effect of gravitation for detection of bronchioloalveolar carcinoma on computed
      tomography.
AB  - A 64-year-old female was found to have localized ground-glass opacity (GGO) in
      the middle lobe on a chest computed tomography (CT) for screening. Middle
      lobectomy with video-assisted thoracoscopic surgery (VATS) was undertaken, and
      pathological diagnosis was a bronchioloalveolar carcinoma (BAC) in stage IA. A
      follow-up CT a year following the surgery revealed localized GGO in area S6 of
      the left lung. However, it disappeared during the gravitation-dependent gradient
      in the observation period. The patient was scanned again under prone position to
      exclude the gravitational effect, resulting in definite detection of the GGO.
      Left extended S6 segmentectomy with VATS was performed, and pathological
      diagnosis was a BAC in stage IA. As GGO existing in a gravitation-dependent area
      may be masked by the gravitation-dependent density, a change of the scanning
      position may lead to a proper detection of the tumor for the diagnosis of BAC.

PMID- 15997754
TI  - Experience of thoracoscopic extirpation of intrapulmonary lymphangioma.
AB  - We report a 59-year-old woman who underwent thoracoscopic extirpation of the
      intrapulmonary cystic lymphangioma which was located in the subpleural space of
      the left upper lobe. A chest X-ray showed a solitary round nodule in the left
      pulmonary hilum. A computed tomography scan revealed a mass shadow at the
      interlobar region surrounding the interlobar pulmonary artery. A round nodule was
      recognized as low signal intensity on T1-weighted images by magnetic resonance
      imaging. There was biphasic signal intensity on T2-weighted images as well.
      Radiologically, we diagnosed this lesion as a benign cystic tumor in the lung.
      Thoracoscopic observation revealed a cystic lesion just beneath the visceral
      pleura of the upper lobe adjacent to the interlobular pulmonary artery. As this
      suggested a benign bronchogenic cyst, we performed extirpation of the cyst under
      thoracoscopy. After this operation, the cyst was diagnosed as an intrapulmonary
      cystic lymphangioma pathologically.

PMID- 15997755
TI  - Cardiac surgery for a patient with familial lecithin: cholesterol acyltransferase
      deficiency.
AB  - A 62-year-old female with familial lecithin: cholesterol acyltransferase (LCAT)
      deficiency was subjected to cardiac surgery consisting of mitral valve repair,
      tricuspid valve annuloplasty, and left atrium plication, under cardiopulmonary
      bypass. Familial LCAT deficiency is a very rare disease with clinical features
      including corneal opacity, hemolytic anemia, and renal failure. Our patient
      manifests partial LCAT activity and no renal failure. Patients with LCAT
      deficiency have fragile red blood cells, renal dysfunction, and disturbed
      metabolism of platelet-activating factor. To date, no record of cardiac surgery
      on patients with LCAT deficiency has been reported. Thus, we present the result
      of this experience to share what we learned about this complicated and rare
      disease.

PMID- 15997756
TI  - Medical education and the training of cardiothoracic surgeons in the United
      States of America.

PMID- 15997757
TI  - Training program for thoracic and cardiovascular surgeons in Canada.

PMID- 15997758
TI  - Training in thoracic and cardiovascular surgery in France.

PMID- 15997759
TI  - Introduction of medical education system and postgraduate cardiovascular surgeon
      training program in China.

PMID- 15997760
TI  - Training of cardiothoracic surgeons in the UK.

PMID- 15997761
TI  - Open heart surgery in a patient with paroxysmal nocturnal hemoglobinuria.

PMID- 15997762
TI  - [Toxic effects and pharmacodynamics of PCB and PCDF in Yusho patients during the
      last 35 years].

PMID- 15997763
TI  - [Steps for establishment of the diagnostic standard in Yusho patients].

PMID- 15997764
TI  - [Concept on the statistically approached new diagnostic standard for Yusho
      patients ].

PMID- 15997765
TI  - [Findings in oral mucosa and teeth of Yusho patients].

PMID- 15997766
TI  - [Neurological symptoms in Yusho patients suffering for the last 36 years].

PMID- 15997767
TI  - [Ophthalmologic findings in Yusho patients].

PMID- 15997768
TI  - [Skin symptoms in Yusho patients related to blood dioxin level].

PMID- 15997769
TI  - [Relationship between blood PCDFs level and symptoms in Yusho patients].

PMID- 15997770
TI  - [Blood chemical analysis and alpha-fetoprotein and HBs analysis in Yusho
      patients].

PMID- 15997771
TI  - [Sex ratio of newborn infants from parents with Yusho].

PMID- 15997772
TI  - [Improvements in the method of dioxin isolation from blood of Yusho patients].

PMID- 15997773
TI  - [Blood cell count and blood chemical analysis in Yusho patients].

PMID- 15997774
TI  - [Possible candidates for the compound which is expected to attenuate dioxin
      toxicity].
AB  - This review deals with the three candidate compounds which may combat with
      dioxins' toxicity. Geranylgeranylacetone (GGA), an antiulcer drug, counteracts
      suppression of body weight gain and lethality produced by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice. Similarly, curcumin, a food
      ingredient anticipates the TCDD's toxicity on body weight gain. Both GGA and
      curcumin had no effect on the induction of hepatic ethoxyresorufin O-deethylase
      activity by TCDD. These data suggest that both compounds exhibit a protective
      effect against some forms of dioxin toxicity by a mechanism without involving
      inhibition of aryl hydrocarbon receptor activation. Further, the mechanism
      involved in resveratrol action on dioxin's toxicity was also discussed. Prior to
      the application of these compounds to Yusho patients, the limitation and
      possibility of these candidate compounds are seemed to be further studied.

PMID- 15997775
TI  - [Examination of urine acrolein in Yusho victims].
AB  - Polychlorinated biphenyls (PCB) causes the release of superoxide during the
      metabolic process. Therefore, Yusho victims are thought to be exposed to
      oxidative stress caused by PCB, because high concentrations of PCB are still
      detected in the serum of Yusho victims. Recently, acrolein (ACR) has been
      reported to be one of excellent markers of oxidative stresses. In order to
      estimate the influence of oxidative stress by PCB, we measured urine ACR in Yusho
      victims and age-matched controls. The mean concentration of urine ACR was 355.4
      +/- 37.2 in Yusho victims and 314.5 +/- 54.6 nmol/ml in controls, respectively.
      Unfortunately, there was no difference in urine concentrations of ACR between
      Yusho victims and controls. ACR is reported to be one of ubiquitous pollutants in
      the environment. It was supposed that PCB can give rise to ACR as an oxidative
      stress, but the influence seemed to be common even in the control subjects who
      had never been exposed to PCB. The exact mechanism is still unclear, and further
      examinations should be conducted in the near future.

PMID- 15997776
TI  - [Evaluation of dermatological symptoms of Yusho patients in the annual
      examination in 2003-2004].
AB  - We evaluated the severity grades and the skin severity scores of the skin
      symptoms who visited the annual examinations of Fukuoka prefecture in 2003 and
      2004. The severity of skin symptoms improved significantly in the first 20 years;
      nowadays, however, further improvement can hardly be observed. More than 36 years
      have passed since the Yusho incident, and about 60% of the patients currently
      present no skin symptoms. In contrast, in about 40% of the patients,
      characteristic skin symptoms of Yusho, such as pigmentation of skin, black
      comedones and acneform eruptions, could still be observed. Using Peason's
      correlation coefficient test and Spearman's correlation coefficient test, we
      analyzed correlation between "PCB pattern" and the blood PCB concentration, the
      skin severity grade and the skin severity scores. However, we could not find out
      any obvious correlation.

PMID- 15997777
TI  - [Congener specific determination of PCBs in human blood using gel permeation
      chromatography (GPC) and high resolution gas chromatography/high resolution mass
      spectrometry (HRGC/HRMS)].
AB  - We studied the progressive analytical method for polychlorinated biphenyls (PCBs)
      in blood samples collected from Yusho patients. This study established a
      systematic procedure for determining both "total concentration of PCBs and their
      profiles" and "concentrations of mono-ortho PCBs as dioxin-like compounds",
      providing a significant index for diagnosis. The method we developed consists of
      a rapid clean-up using gel permeation chromatography (GPC) and sensitive
      identification with high resolution gas chromatography/high resolution mass
      spectrometry (HRGC/HRMS). This method provides identification of all of PCB
      congeners typically detected in human blood samples, especially it is worth
      noting that nine significant congeners on Yusho diagnosis (IUPAC #105, #114,
      #118, #123, #153, #156, #157, #167, #189) were detected from a five-gram blood
      sample. Using the present method, we analyzed sixty-six individual blood samples
      collected during the annual Yusho inspection in the 2004, and could identified
      sixty-eight PCB isomers in all samples. As a result, ten patients were classified
      into pattern A, the typical Yusho pattern. The mean total PCB concentration of
      pattern A subjects was 2.95 ppb, while that of control subjects was 0.77 ppb, at
      whole blood basis respectively.

PMID- 15997779
TI  - [Metabolism of 2, 3', 4, 4', 5-pentachlorobiphenyl in guinea pig microsomes].
AB  - The in vitro metabolism of 2,3',4,4',5-pentachlorobiphenyl (pentaCB) (CB118) was
      studied using liver microsomes of guinea pigs and the effect of cytochrome P450
      inducers, phenobarbital (PB) and 3-methylcholanthrene (MC) on CB118 metabolism
      was also compared. After 30 min-incubation at 37 degrees C with liver microsomes
      of guinea pigs, CB118 was hydroxylated to two metabolites (M(-1) and M(-2)) with
      retention times of 15.84 min and 20.01 min in GC/ECD, respectively. GC/MS showed
      that the methylated derivative of a major metabolite M(-2) had the molecular
      weight of 354 and an intense fragment ion of [M(+)-50] which is a characteristic
      ion for PCBs possessing a methoxy-group at the 2 (2')- or the 6 (6')-position. By
      comparison of the mass fragmentation and the retention times in GC/MS with the
      synthetic authentic compounds, M(-2) was identified as 2-hydroxy-3,3',4,4',5
      pentaCB (CB126). On the other hand, the methylated derivative of a minor
      metabolite M(-1) had the molecular weight of 320 and the similar fragment ion of
      [M(+)-50] to the methylated M(-2), assuming that M(-1) was a dechlorinated
      monohydroxy-tetrachlorobiphenyl (tetraCB) possessing hydroxy-group at the 2 (2')-
      or the 6 (6')-position. However, the precise structure of M-1 could not be
      determined because its retention time in GC was in disagreement with that of the
      candidate 6-hydroxy-3,3',4,4'-tetraCB. PB-treatment increased the formation of M(
      1) and M(-2) to 2.2- and 6.8-fold of untreated animals, whereas MC-treatment
      increased only M(-2) to 2.6-fold of untreated ones. Addition of antiserum against
      a PB-inducible guinea pig cytochrome P450, CYP2B18, completely inhibited the
      formation of M(-2). These results suggest that CB118 is principally metabolized
      by CYP2B18 to 2-hydroxy-CB126 which is formed via a 2,3-epoxide intermediate and
      the subsequent NIH-shift of a chlorine at the 2-position to the 3-position in
      guinea pig liver.

PMID- 15997778
TI  - [Analysis of polychlorinated quaterphenyls in Yusho diagnosis].
AB  - The polychlorinated quaterphenyl (PCQ) concentrations in the blood are important
      discriminative parameters in Yusho patients. In this study, the analytical method
      of PCQ was improved, and a high speed and precision analysis could be achieved. A
      recovery test showed satisfactory recoveries of 99.5% (RSD4.8%, n = 5). Using
      this method, the authors analyzed 62 blood samples which were collected from the
      2004 annual inspection for Kanemi rice oil poisoning. PCQ was detected in 20
      blood samples (ranging from 0.03 to 4.15 ng/g). The average concentration was
      2.07 ng/g in the pattern A (typical Yusho patients), 0.76 ng/g in the pattern B,
      0.18 ng/g in the pattern BC and 0.01 ng/g in the pattern C, respectively.

PMID- 15997780
TI  - Promotive excretion of causative agents of Yusho by one year intake of FBRA in
      Japanese people.
AB  - Thirty-six years have passed since the outbreak of Kanemi rice oil poisoning,
      namely, Yusho in the western Japan. However, even now the patients with Yusho
      have been still suffering from several objective and subjective symptoms. In
      order to improve or, if possible, to cure the such symptoms, the most important
      therapeutic treatment is considered to actively excrete the causative agents,
      that is, polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p
      dioxins (PCDDs) from the bodies of the patients and to reduce their body burdens.
      In rats, dietary fiber and chlorophyll have been shown to promote the fecal
      excretion of dioxins and to reduce their levels in rat liver. In this study, we
      examined whether such kinds of effect were also observed by FBRA, which was the
      health food and relatively rich with dietary fiber and chlorophyll, in nine
      married Japanese couples. As a result, concentrations of PCDFs and PCDDs on the
      lipid weight basis in the blood of the FBRA-intake group in which they took 7.0
      to 10.5g of FBRA after each meal and three times a day for one year were more
      lowered than those in the blood of the non-intake group; Blood levels of PCDFs
      and PCDDs in the FBRA-intake group were decreased by 41.0 and 37.2%,
      respectively, and those decreases were 33.7 and 29.4% in the non-intake group.
      Their total body burdens just before and one year after the study were calculated
      on the assumptions that the body fat was also contaminated with these dioxins at
      their blood levels on the lipid weight basis and the content of body fat was 20%
      of the body weight. Then, we computed the average amounts in excretion of PCDFs
      and PCDDs from the body in both the FBRA-intake and non-intake groups.
      Consequently, the amounts of excretion of PCDFs and PCDDs in the FBRA-intake
      group were 1.81 and 1.74 times, respectively, greater than those in the non
      intake group. Therefore, FBRA seemed to promote the fecal excretion of causative
      agents of Yusho, from the human body. We also expect FBRA to reduce their body
      burdens of patients with Yusho and to improve some objective and subjective
      symptoms of Yusho patients.

PMID- 15997781
TI  - Follow-up survey of dioxin concentrations in the blood of Yusho patients in 2002
      2003.
AB  - We measured the concentrations of polychlorinated dizenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), and non-ortho-coplanar polychlorinated
      biphenyls (Co-PCBs) in blood collected from 279 Yusho patients and 92 Yusho
      suspected persons living in Japan in 2002, 269 Yusho patients and 74 Yusho
      suspected persons living in Japan in 2003 and 128 normal controls living in
      Fukuoka Prefecture, and compared with the concentrations of these compounds among
      the groups. The total TEQ concentrations of PCDDs, PCDFs, and Co-PCBs in the
      blood of Yusho patients were 3.6 times and 3.3 times higher than those in the
      normal controls in 2002 and 2003, respectively. In the case of Yusho-suspected
      persons, the concentrations were 1.1 times and 1.0 times higher in 2002 and 2003,
      respectively. Among the TEQ concentrations of PCDDs, PCDFs, and Co-PCBs, the
      concentrations of PCDFs in the blood of Yusho patients were 10.3 times and 9.4
      times higher than those of the normal controls in 2002 and 2003, respectively,
      whereas the concentrations of PCDDs and Co-PCBs in blood were identical in Yusho
      patients, Yusho-suspected persons and normal controls. Yusho patients indicated
      the highest concentrations ratio of PCDFs to the total TEQ concentrations.
      Moreover, of the PCDFs congeners for Yusho patients, the concentrations of
      2,3,4,7,8-PeCDF were about 11.0 times and 10.1 times higher in 2002 and 2003 than
      those in normal controls. These results indicated that Yusho patients have a much
      higher concentration of 2,3,4,7,8-PeCDF in their blood than do unaffected persons
      even though over 34 years have passed since the outbreak of Yusho.

PMID- 15997782
TI  - [Role of gastro-esophageal reflux (GER) and swallowing latency in aspiration
      pulmonary diseases].
AB  - We evaluated the role of gastro-esophageal reflux (GER) in aspiration pulmonary
      disease. To explore swallowing function, we measured the latent time (LT) on the
      swallowing provocation test in patient with non-aspiration pneumonia (PN, n=5),
      aspiration pneumonia (AP, n=8), post-gastrectomy aspiration pneumonia (PGAP,
      n=8), gastro-esophageal reflux disease (GERD, n=12) and normal group (NR, n=7).
      LT was prolonged in the AP (2.83 +/- 1.66 sec p < 0.01), PGAP (2.58 +/- 1.40 sec
      p < 0.05) and GERD (2.40 +/- 1.70 sec p < 0.05) groups compared with NR (1.04 +/-
      0.56 sec) group, but not prolonged in PN (1.46 +/- 0.75 sec) group. LT was also
      prolonged when swallowing was provoked during inspiration both in AP (3.61 +/-
      2.60 sec vs. 2.73 +/- 2.19 sec, p < 0.05) and NR (2.13 -/+ 1.12 sec vs. 1.49 +/-
      1.30 sec, p < 0.01). Protected specimen brushing (PSB) was employed to detect
      pathogenic organisms in the PN (n=70), AP (AP, n=27) and PGAP (n=15) groups. Gram
      negative rods were most frequently detected in the PGAP (p=0.008) group. We
      conclude that GER plays an important role in aspiration pulmonary disease not
      only as a source of aspirating agent but also as a disturbing factor of
      swallowing function.

PMID- 15997783
TI  - [Infection control in a teaching hospital without a tuberculosis ward].
AB  - Approximately 30 cases of tuberculosis are diagnosed in our hospital each year.
      Because three of our nurses contracted tuberculosis in 1998, we implemented the
      following control measures for tuberculosis : (1) immediate examination,
      diagnosis, and treatment in suspected cases; (2) screening of all health-care
      workers with a two-step tuberculin skin test (TST); (3) examination of all
      persons exposed to tuberculosis-infected persons; and (4) greater awareness of
      tuberculosis. We offered prophylactic medications to all exposed persons with a
      TST reaction greater than 20 mm. These control measures increased the numbers of
      outpatients who were examined and treated, and decreased the prevalence of
      tuberculosis among long-term inpatients. High-risk indices also decreased over a
      2-year period. Forty-seven staff members showed TST reactions, and 5 of them
      received prophylactic medication. No cases of tuberculosis developed in staff
      members exposed to tuberculosis-infected persons. However, tuberculosis developed
      in one staff member who had a strong TST reaction at the start of employment. In
      this case, results of TSTs previously administered to all health-care workers was
      useful for estimating the prevalence of infection. We used a new method for
      diagnosing tuberculosis in 27 persons believed to be infected. Of these 27
      persons, 5 (19%) showed reactions greater than pseudopositive reactions and were
      given prophylactic medication. Early diagnosis of infected persons, examination
      of persons exposed to tuberculosis, and greater disease awareness are important
      measures for monitoring tuberculosis and controlling its spread.

PMID- 15997784
TI  - [Measurement of diffusing capacity by the intrabreath method].
AB  - The diffusing capacity of the lung for carbon monoxide (DLco) is usually measured
      by the single breath method with a 10-second breath hold. With the introduction
      of rapid gas analyzers, an alternative method for measurement of DLco, the
      intrabreath method, has been developed. The intrabreath method does not depend
      upon length of time or other conditions during either breath holding or
      expiration. The aim of this study was to compare the single breath method and
      intrabreath method of DLco measurement. DLco measured by the intrabreath method
      (DLco IB) was compared with DLco measured by the single breath method (DLco SB)
      in 32 normal subjects, 88 patients with obstructive impairment and 39 patients
      with restrictive impairment. DLco SB could not be measured in 2 patients with
      obstructive impairment and 7 patients with restrictive impairment, while in all
      except one patient with severe restrictive impairment, DLco IB was able to be
      measured. There was an excellent correlation between DLco IB and DLco SB in
      normal subjects (rho = 0.942, p < 0.0001). There was no difference in the mean
      value between DLco IB (21.0 +/- 5.4 ml/min/mmHg) and DLco SB (20.9 +/- 4.9
      ml/min/mmHg). In the obstructive impairment group there was also an excellent
      correlation between DLco IB and DLco SB (rho = 0.922, p < 0.0001). In the mild or
      moderate obstructive impairment group (%FEV1 > 50%), no difference between DLco
      IB (11.8 +/- 5.80 ml/min/mmHg) and DLco SB (12.4 +/- 4.68 ml/min/mmHg) was found.
      In the severe obstructive impairment group (%FEV1 < 50%), the DLco IB (7.29 +/-
      3.61 ml/min/mmHg) was lower than the DLco SB (8.58 +/- 3.24 ml/min/mmHg) (p <
      0.0001). The relation between DLco SB and DLco IB was equally strong in patients
      with restrictive impairment (rho = 0.742, p < 0.0001). There was an excellent
      correlation between DLco IB and DLco SB in normal subjects, the obstructive
      impairment group and the restrictive impairment group. The intrabreath method
      therefore seems to be a useful and reliable alternative to the single breath
      method for clinical measurement of DLco.

PMID- 15997785
TI  - [A case of primary pulmonary hypertension treated by long-term continuous
      administration of epoprostenol].
AB  - A 50-year-old man was urgently transferred to another hospital due to
      unconsciousness diagnosed as due to primary pulmonary hypertension following
      cardiac catheter test and pulmonary blood flow scintigraphy. He was referred to
      our hospital for treatment of hypoxemia. Thereafter, he was treated by home
      oxygen therapy and home epoprostenol therapy, although he required frequent
      admissions. During treatment, problems consisting of self-evulsion and infection
      of the insertion site occurred. Changes in symptoms, arterial blood gas analysis,
      serum BNP and ultracardiography were useful for managing home epoprostenol
      therapy. We reported a case of primary pulmonary hypertension treated by long
      term continuous administration of epoprostenol for about 6 years and 9 months.

PMID- 15997786
TI  - [A case of natural killer cell lymphoma with high adenosine deaminase level in
      pleural effusion].
AB  - A 61-year-old man was admitted to our hospital with cough, breathlessness,
      anorexia and chest pain. Chest radiograph showed right pleural effusion and also
      a chest CT scan showed right pleural effusion with thickening of the right
      visceral pleura, pericardial effusion and a liver tumor. The pleural effusion was
      slightly bloody and exudative. The adenosine deaminase (ADA) level in the pleural
      effusion was elevated. Because the cytological examintion of the pleural effusion
      showed no malignancy, we diagnosed pleuritis tuberculosa. The serum-soluble
      interleukin-2 receptor level was also elevated. His general condition worsened in
      spite of the chemotherapy with antibiotics and antituberculous drugs. We finally
      diagnosed the case as natural killer (NK) cell lymphoma from CT-guided needle
      biopsy just before death, and necropsy. In this case, the high level of ADA in
      the pleural effusion suggested lymphoma.

PMID- 15997787
TI  - [Two cases of mature mediastinal teratoma complaining of sudden chest pain].
AB  - We report two cases of mature mediastinal teratoma complaining of sudden chest
      pain. Both cases had cystic lesions, multilocular and unilocular, and pleural
      effusion. One case had fat density by CT and MRI and calcification was not
      recognized in either case. Surgical resection of the tumor revealed pancreatic
      tissue in both cases, suggesting that pancreatic enzymes might have led to the
      rupture of the tumor. The diagnosis of teratoma and its rupture should be
      considered in the cases of cystic lesion in mediastinal with sudden onset of
      chest pain.

PMID- 15997788
TI  - [An elderly case of sarcoidosis with multiple pulmonary cysts].
AB  - We report an elderly case of sarcoidosis with multiple pulmonary cysts. An 80
      year-old woman was admitted to our hospital for detailed examinations of multiple
      cysts in both lungs. Chest radiography and chest CT revealed multiple cystic
      lesions with thin walls which were clearly separated from normal lung. A
      transbronchial lung biopsy revealed epitheloid cell granuloma, indicating
      sarcoidosis. Although elderly cases of sarcoidosis with multiple pulmonary cysts
      are very rare, sarcoidosis should be considered in the differential diagnosis.

PMID- 15997789
TI  - [Pulmonary nocardiosis complicated with multiple brain abscess].
AB  - A 52-year-old woman was taking 10 mg of prednisolone on alternate days for the
      treatment of autoimmune hemolytic anemia. She was informed of an abnormality on a
      chest X-ray film about 3 months previously and was admitted to our hospital with
      sudden onset of chest pain and fever. On the following day, she underwent
      transthoracic needle biopsy and the lung lesion was diagnosed as pulmonary
      nocardiosis. She showed improvement of fever and the lung lesion with
      administration of an antibacterial agent, but suddenly developed vomiting and
      headache. Brain MRI revealed multiple brain abscesses at more than 20 sites. A
      subsequent change of the antibacterial agent achieved control of the lung lesion
      and brain lesions. This case shows that prednisolone can cause nocardiosis as an
      opportunistic infection even at a low dose and that antibacterial agents act
      differently on the lung and brain lesions caused by this organism.

PMID- 15997790
TI  - [A case of allergic bronchopulmonary aspergillosis followed by diagnostic imaging
      for 27 years].
AB  - This patient was a 28-year-old man who had been treated with steroids for
      recurrent asthmatic attacks since around the age of 20. At one time the steroid
      therapy was discontinued and other treatments, including bronchodilator therapy
      and desensitization therapy, were substituted. At age 28, he first consulted our
      hospital due to the recurrence of attacks. We found peripheral eosinophlia and a
      cytologic examination revealed Curschmann spirals in his sputum. Migratory
      infiltrate recurred, and steroids and antibiotics were prescribed each time. A
      confirmed diagnosis of allergic bronchopulmonary aspergillosis was made at age
      35. The patient was treated with continuous oral steroids for recurrent
      infiltrates. After the start of inhale steroid therapy at age 44, the frequency
      of attacks decreased and tapering of the oral steroids became possible. It is
      notable that lung tissue destruction progressed by recurrent pneumonia and
      emphysema extended into all portions of the lung. Furthermore, this case history
      is of value since it yields a series of images taken over a period of 27 years.

PMID- 15997791
TI  - [A case of Osler-Weber-Rendu syndrome: therapeutic embolization of the pulmonary
      artery and bronchial artery].
AB  - We encountered a case in which the symptoms of hypoxia and hemoptysis improved
      after performing repeated pulmonary artery embolizations and bronchial artery
      embolization. A 22-year-old man was hospitalized in our institution with high
      fever, headache and unconsciousness in May of 2001. Subendocranial abscess was
      diagnosed, so we performed antibiotic therapy and drainage, but at that time he
      showed symptoms of hypoxia. We diagnosed Osler-Weber-Rendu syndrome because of
      multiple small nodular shadows in his chest CT, multiple arteriovenous fistulae
      in both lungs on pulmonary arteriography, and telangiectasis. We performed
      pulmonary artery embolization 6 times, and his hypoxia and right to left shunts
      improved. In the course of our therapy, hemoptysis appeared and dilatation of
      vessels was detected in the left bronchial arteriography, so we performed
      embolization of the left bronchial artery and the symptom improved. We concluded
      that we should take care to detect not only pulmonary arterial lesions but also
      bronchial arterial leisions in the diagnosis and therapy of respiratory symptoms
      of Osler-Weber-Rendu syndrome.

PMID- 15997792
TI  - [Nursing care given to children aged less than one year at a basic district
      health unit].
AB  - This study is characterized as descriptive and exploratory, based on the
      observation of nursing care at the sectors of vaccination, pre- and post
      consultation, and first aid at a basic district health unit in the city of
      Ribeirao Preto, state of Sao Paulo, Brazil. The purpose of this observation was
      the characterization and understanding of the nursing care given to children aged
      less than one year and the follow-up of their growth and development, as
      previously approved by a Research Ethics Committee. Thirty-two children,
      accompanied by their mothers, participated in the study, totaling 56 hours of
      observation. In general, the set of assistance episodes allowed the comprehension
      of nursing guidelines in vaccination and the follow-up of the child, which has
      shown the need to expand care and introduce the strategy of Integrated Management
      of Childhood Illness.

PMID- 15997793
TI  - [Nutritional evaluation of children aged from six to sixty months].
AB  - This study aims at identifying the nutritional situation of children aged between
      six and sixty months. Two methodologies were used to determine the children's
      nutritional status: Waterloo criteria and the weight/age curve on the Child's
      Card. The prevalence of nutritional problems was of 42.9%, according to Waterloo
      criteria, and 35.6% when the weight/age curve was used. Educational actions are
      proposed so that the family may adopt behaviors and life styles aiming at
      reducing the risks on the child's growth and development Descriptors: nutritional
      assessment; malnutrition; child TITLE: Nutritional evaluation of children aged
      from six to sixty months

PMID- 15997794
TI  - [Birth center, symbols and assistance-related principles].
AB  - The first Birth Center of the Family Health Program has specific symbols. The
      purpose was the identification of symbols that permeate the ideas, beliefs,
      values, practices, and principles that guide the assistance given at the Birth
      Center. Ethnography was the research method; thematic oral history was the
      resource employed to interview obstetric nurses in the House. RESULTS: The House
      has the symbolic value of innovation in assisted deliveries. Humanized care to
      pregnant women is the principle that guide practices. FINAL CONSIDERATIONS: The
      symbols of the House and the care practices developed constitute a reference to
      the other birth centers being proposed in Brazil, and should be known by
      obstetrical nurses.

PMID- 15997795
TI  - [Family dynamics, stages of the elderly with Alzheimer disease, and stages
      experienced by the family in relation to home care].
AB  - A qualitative research carried out with relatives who take care of elderly people
      with Alzheimer disease, it aimed at describing the experiences of these family
      members in living with the elderly and analyzing aspects that interfere with the
      transformations of family dynamics since the onset of the disease. The concept of
      dialogical education was applied to produce data in the dynamics of creativity
      and sensitivity Subjects shared the reality of living with the diseased person in
      the most diverse situations of life, their feelings, their anguish, interpersonal
      relationship, their expectations and family members' strategies in home co
      existence. It was commented that the different stages of the diseased person and
      his/her family members, respectively, even though not always coinciding, are
      interpenetrated, thus generating transformations and re-configuration in family
      dynamics.

PMID- 15997796
TI  - [Nursing and the family program: a successful partnership?].
AB  - This was a qualitative, descriptive study that analyzed the work of the nursing
      staff in the Family Health Program (PSF: Programa Saude da Familia) in Campinas
      from 1998 to 2002. As reference, nursing is defined as work. The study was based
      on interviews with ten workers from the first three family health teams.
      Thematically, the following issues were addressed: nursing work and team work,
      emphasizing the activities developed and the nursing work process. Nursing and
      PSF is a successful partnership that needs to be explored and addressed. By
      assessing this production of knowledge and procedures, it is possible to identify
      how broad the work of Brazilian nursing is in Family and Public Health.

PMID- 15997797
TI  - [When a nurse assesses the care of a patient under parenteral nutrition].
AB  - The present study aimed at understanding the nurses' experiences by assessing the
      process of caring for a patient under parenteral nutrition. We used symbolic
      interactionism and a data-based theory as a theoretical and methodological
      referential. Ten nurses that experienced this practice in a public hospital in
      Fortaleza, state of Ceara, took part. Data collection took place during the
      period from April 1st to December 30th, 2001 through participatory observation
      and semi-structured interviews. We identified the phenomenon "Assessing the
      process of caring for a patient under parenteral nutrition" which expresses the
      nurse's experiences by showing attitude, feelings and meanings for care.

PMID- 15997798
TI  - [Course of specialization in nursing residence].
AB  - This study focuses on resident nurses from the Course of Specialization in
      Nursing Residence at UNIRIO. It aims at identifying the importance of the classes
      offered by the Course of Nursing Residence for a professional career by checking
      whether the Course has influenced towards the inclusion of the resident nurse
      into the job market; and identifying the areas of specialty chosen at the moment
      of the selection for the course by resident nurses that finished the five first
      groups. The study was carried out with resident nurses that were in the first
      five groups of the Course. Results show that specialization makes it possible for
      the professional to get qualified and acquire specific knowledge in the area of
      specialty chosen.

PMID- 15997799
TI  - [Identifying factors related to the diagnosis "risk of falls" among the elderly
      in a microarea].
AB  - Considering that falls, among the elderly, represent a relevant public health
      issue, this study aims at identifying factors related to the nursing diagnosis
      "risk of falls" among 51 elderly people who reside in a microarea. Results have
      showed that all the elderly had the nursing diagnosis "risk of falls" related to
      many intrinsic and extrinsic factors. The knowledge of this population's needs
      shows how important the adoption of educational, individual and collective
      measures aiming the maintenance of their health level is.

PMID- 15997800
TI  - [Gender indicators of nursing care for women].
AB  - This text presents a study-carried out at a healthcare unit in Salvador/Bahia,
      with the purpose of building quality indicators for nursing care from a gender
      perspective. The construction of the indicators occurred by means of an
      investigation that analyzed women's ideas about the pre-natal nursing assistance
      provided to them, based on the identifications of actions that promote autonomy,
      merit, and participation. Data collecting was based on a semi-structured
      interview with 14 women that are users of prenatal nursing care and accepted to
      participate in this study and had also been cared by a nurse in a previous
      pregnancy or during the present one. Two kinds of gender indicators in nursing
      care were built: practical indicators and strategic gender indicators.

PMID- 15997801
TI  - [The nurse's role as an educator toward people who care for BVA patients].
AB  - This article was written based on bibliographical research aiming at making a
      thematic analysis of the production of knowledge in newspapers and magazines
      about the nurse's role as an educator toward people who care for BVA (brain
      vascular accident) patients. The analysis gathered articles published in the 80's
      and 90's, from the Medline, Lilacs and Cinahl databases. Content analysis was the
      methodological background that allowed the organization of knowledge in two
      categories: educational intervention in the acute stage and the post-discharge
      support.

PMID- 15997802
TI  - [Nursing research at the Congress on Scientific Initiation in a university in the
      city of Sao Paulo].
AB  - The objective of this descriptive study was to evaluate the methodological
      accuracy of the studies presented by the Nursing Faculty in the 5h Congress on
      Scientific Initiation in a university in the city of Sao Paulo, based on a
      summary published in the event annals and on the posters presented there.
      Considering the 42 works, the objectives were adequately constructed in 45.2%,
      while 31% were not clear and not able to be evaluated. More than one
      methodological inadequacy was observed for the same work, totaling 56
      occurrences. The results showed to be adequate in 24 works. 33.3% of the works
      had adequate conclusions, followed by 31.5% which did not meet the objectives of
      the study. Ethic questions in research were not mentioned in 64.3% of the works.
      When comparing works of the same subject performed by other Brazilian
      researchers, results indicate that the research activity in this Nursing Faculty
      needs more investment regarding qualification of the professors-orientators to
      fulfill the need of strengthening the activity.

PMID- 15997803
TI  - [Presence of the sacred in a critical moment: internment in an unit of intensive
      therapy].
AB  - It is had as purpose understands the given meaning, for the patient, to the
      sacred object in a moment of internment in Unit of Intensive Therapy. Stands out
      forms of expression of the sacred in a critical instant in which the man in state
      of physical-emotional fragility, looks for answers transcendental front the
      anguish of the disease and of dying. The sacred is a trick of the religion
      through which the man tends taking refuge of the installed chaos. The presence of
      the sacred object, close to the patient, represents an event of immeasurable
      cultural meaning, being revealed in a supra-natural entail of which exhales hope,
      safety, help, comfort and, even, company.

PMID- 15997804
TI  - [Health family program: profile of elderly people assisted by a team].
AB  - This exploratory research investigated the profile of elderly people assisted by
      a team of the Family Health Program (FHP) in Goiania, in 2003. 75 elderly people
      participated, who were examined and interviewed. Female prevalence was identified
      (68%) as well as of people aged 60-64, married or widows/widowers, illiterate or
      semi-literate individuals, those who live with someone else (92%), indicated
      arterial hypertension (64%), pain (68%), and had no cognitive alteration (80%).
      Considering that some of these results are different from the literature, it is
      necessary that the teams of FHP carry out a study of the population of their
      respective areas of comprehension, in order to act in a more assertive way.

PMID- 15997805
TI  - [The psychiatric reform in Distrito Federal].
AB  - This paper studies the configuration of institutional practices and their
      historical determinations at Hospital Sao Vicente de Paulo-HSVP reference
      hospital in the Federal District for psychiatric treatment, from 1985 to 2002. A
      qualitative research was chosen, using a historical-structural approach and case
      study technique. The authors elected ideology as analytical category and, as
      empirical categories, mental health care and the psychiatric reform. The research
      tools used were interviews with key informants and institutional subjects (16
      health professionals, 12 clients and 9 family members), analysis of documents and
      interactive observation. The authors concluded that, from 1999 onwards, mental
      health practices at HSVP have suffered a retraction in regards to the Psychiatric
      Reform, as the hospital has implemented its policy of desinstitulization, but at
      the same time has submitted its clientele, patients and families to a situation
      characterized by poor medical assistance and social exclusion.

PMID- 15997806
TI  - [Normal births experiennced by adolescents].
AB  - Qualitative study based on experiences by teachers and assistants. It has as
      object the experience of normal birth by a primiparous adolescent, aiming at
      understanding this experience, based on the phenomenological method.

PMID- 15997807
TI  - [Nursing diagnoses and intervention for patients under anticoagulant therapy].
AB  - Patients under treatment with oral anticoagulants present specific needs for
      which nursing care plays an important role, especially to prevent complications.
      The present review was carried out aiming at discussing nursing diagnoses for
      these patients by using the system of the North American Nursing Diagnoses
      Association--NANDA. Diagnoses for such patients depict the risk of bleeding and
      rethrombosis almost always due to the ineffective control of the therapeutic
      regimen and the deficit in the volume of fluids during active bleeding. Also,
      nursing interventions and assessment criteria are proposed for such conditions.
      The authors see the team's preparation to deal with such therapy as relevant for
      successful assistance.

PMID- 15997808
TI  - [Permanent education in the context of nursing and health].
AB  - In this essay authors discuss the current proposal of permanent education by the
      Health Ministry, which is focused on the formation of human resources for the
      Public Health System. It covers education as a whole and specifically adult
      education, an issue that directly affects nursing, as nursing contributes with
      the largest number of healthcare workers, constituting the central focus of
      public policies. In this way authors present the main controversies and suggest
      adherence to the government program, understanding that for the first time there
      is a comprehensive project in this area that is intended to be permanent.

PMID- 15997809
TI  - [Content analysis: a qualitative data analysis tool in health care].
AB  - The content analysis method utilizes various techniques for qualitative data
      analysis. However, for a novice researcher or one who is unfamiliar with this
      technique, understanding and applying this method has proved to be difficult.
      Therefore, this study was undertaken with the purpose of clarifying important
      concepts and aspects of this method as well as discussing its core points. The
      content analysis method was systematized during the first half of the twentieth
      century and, at first, it was an important tool for analyzing articles and
      advertisements published by the media in the United States. Presently, it is
      widely used in scientific research in the field of health care.

PMID- 15997810
TI  - [Bioethics].
AB  - Bioethics is a new field of knowledge and a current of thought that has been
      largely developing in Brazil, especially since the Nineties. In this article, we
      try to contextualize its inception by justifying the need to create such a
      neologism, since ethics was somewhat forgotten, in relation to the technique,
      being restricted to professional ethics. We are nowadays faced with a wide scope
      of works in this area that help guide our action as citizens who want quality of
      life and to preserve life on the planet. Bioethics, however, is concerned about
      the way of being: thought-judgment-action, in relation to human beings among them
      and towards nature.

PMID- 15997811
TI  - [Health education as a strategy to ensure the human being's dignity].
AB  - It is a theoretical, reflexive study linked to the institutional research project
      named "Nursing Social Responsibility: from the meaning of person to bioethical
      paradigms." OBJECTIVE: Discussing health education as a strategy to ensure the
      human being's dignity. METHODOLOGY: It was based on a qualitative approach, in
      view of the identification and analysis of the theoretical elements obtained in
      the bibliographic surveys for the foundations of the study constituted as one of
      the preliminary aspects of the research. RESULTS: The following were identified
      as theoretical elements: human dignity, its relation with humanization,
      fundamental human rights, and the international declarations to ensure them;
      human action; preliminary strategy for ensuring the dignity of the person.
      CONCLUSION: While health is being furthered through nursing by means of
      dialogical strategies on health education, the person is being respected as a
      dignified, free and autonomous human being, fundamental human rights are being
      taken into account and ensured, therefore contributing to the humanization of the
      areas where health services are developed.

PMID- 15997812
TI  - [Implantation of a videoconferencing system applied to nursing research and
      teaching environments].
AB  - Describes the trajectory followed by a research group at the Ribeirao Preto
      College of Nursing-USP to implant a research/teaching/continuous education
      project based on videoconferencing technology. The technical characteristics of
      the available systems are discussed, as well as the technological solution that
      was adopted in this project to attend to the needs of the academic and research
      environment as well as in the hospital context.

PMID- 15997813
TI  - [The selection process in a graduate course on psychiatric nursing: a
      discussion].
AB  - The goal of this study is to describe and discuss the student selection process
      in the last three years by analyzing the formation and range of professional
      practice of the candidates through a descriptive exploratory study. The analysis
      of the curriculum of candidates reveals a high proportion without a previous
      degree and/or experience in the area. Based on the analysis of data obtained, we
      emphasize the importance of adjusting the program to the profile of students that
      enter the field without previous knowledge or restricting the program for
      professionals that are looking for an in-depth knowledge of mental health.

PMID- 15997814
TI  - [Home visit--the perspective of the psychiatric nursing].
AB  - The home visit is a matter of concern in diverse areas of nursing. With the
      implementation of psychiatric services in the community, the need for visits has
      become evident. For one year, we were involved with this activity, requesting it
      or providing it for patients assisted in the Nucleo de Saude Mental (Mental
      Health Center). The aim of this paper is to describe our experience, detailing
      the following aspects: the public and private life of the family and the
      collaboration between professionals and resources in the community. Home visits
      bring the team closer to the diseased person's context and favor articulation
      among him/her, his/her family, the health center and community resources.

PMID- 15997815
TI  - CAN member tools: the right to accept or reject an assignment.

PMID- 15997816
TI  - Coral diseases on Philippine reefs: genus Porites is a dominant host.
AB  - While it is generally assumed that Indo-Pacific reefs are not widely affected by
      diseases, limited data suggest a number of diseases and syndromes that appear to
      differ from those currently under study in the Caribbean. This report presents
      the results of a baseline survey of coral diseases in 2 regions in the
      Philippines: the Central Visayas and the Lingayen Gulf. Mean prevalence for all
      diseases observed was 8.3 +/- 1.2% (mean +/- SE; n = 8 reefs), with Central
      Visayas reefs showing higher disease prevalence (11.6 +/- 2.8%; n = 4 reefs) than
      those of Lingayen Gulf (5.1 +/- 1.4%; n = 4 reefs). Five diseases and syndromes
      were described; 3 of these-Porites ulcerative white spot disease (PUWS)
      (prevalence = 8.96 +/- 2.2%), tumors (prevalence = 1.0 +/- 0.5%) and pigmentation
      response (prevalence = 0.5 +/- 0.2%)--occurred frequently in both regions and
      targeted the genus Porites. Correlation between disease prevalence and number of
      Porites colonies was fairly strong (r2 = 43.4), though not significant, and no
      correlation was seen between prevalence and either the amount or diversity of
      hard coral. Porites is a major reef-builder in the Indo-Pacific comprising 30% of
      hard coral colonies on our surveyed reefs, and is generally thought to be a
      hardy, long-lived genus. Diseases targeting this robust group present an as yet
      unquantified risk to Philippine reefs and could result in major changes in reef
      structure.

PMID- 15997817
TI  - Phylogenetic analysis of the major capsid protein gene of iridovirus isolates
      from cultured flounders Paralichthys olivaceus in Korea.
AB  - In 2003, 13 isolates of iridovirus were obtained from cultured flounders
      Paralichthys olivaceus during epizootics in Korea. The full open reading frames
      (ORFs) encoding the major capsid protein (MCP) (1362 bp) from the 13 flounder
      iridoviruses (FLIVs) were sequenced and the deduced amino acid sequences were
      phylogenetically analyzed. Phylogenetic analysis of the MCP revealed that all 13
      FLIVs were the same species as rock bream iridovirus (RBIV), red sea bream
      iridovirus (RSIV), and infectious spleen and kidney necrosis virus (ISKNV), and
      were grouped into an unknown genus which was different from the 2 genera known to
      infect fish, Ranavirus and Lymphocystivirus. This is the first report on the
      isolation and phylogenetic analysis of the iridovirus of unknown genus from
      flounders during epizootics.

PMID- 15997818
TI  - Characterisation of surface blebbing and membrane vesicles produced by
      Flavobacterium psychrophilum.
AB  - The surface of Flavobacterium psychrophilum was examined by electron microscopy
      to determine if previous findings of haemagglutination positive (HA+) and
      haemagglutination negative (HA-) abilities could be correlated with expression of
      pili or of a capsular layer. A thin capsular layer was observed in both HA+ and
      HA- strains but typical pili were absent. However, long, tubular blebs that
      released membrane vesicles (MVs) into the supernatant were observed on up to 94%
      of cells within 1 sample. The surface blebbing was increased for 1 strain
      following growth on media with restricted iron availability. The MVs had an
      intact membrane bilayer and were released from blebbing cells of both strains.
      The protein profiles of MVs, while containing some banding similarity with the
      profile of outer membrane preparations (OMPs) and of lysed whole cells (WCs),
      showed several bands that reacted strongly with rabbit anti-whole-cell antisera.
      Two distinct bands of approximately 62 and 58 kDA were highly expressed in the
      MVs and not seen in the OMP. MVs contained proteolytic activity towards gelatine
      but not towards casein and elastin, which were only degraded by live cells. Low
      molecular weight lipopolysaccharides (LPS) or lipooligosaccharides (LOS) were
      associated with the MVs. Only the MVs of the HA+ strain possessed haemagglutinin
      activity. These findings suggest that the F. psychrophilum may, through surface
      blebbing, release antigenic MVs that contain some proteolytic activity and may
      aid the bacterium in releasing nutrients from its surrounding environment as well
      as playing a role in impeding the immune response of its host.

PMID- 15997819
TI  - Standardization of a broth microdilution susceptibility testing method to
      determine minimum inhibitory concentrations of aquatic bacteria.
AB  - A multiple laboratory study was conducted in accordance with the standards
      established by the Clinical and Laboratory Standards Institute (CLSI), formerly
      the National Committee for Clinical Laboratory Standards (NCCLS), for the
      development of quality control (QC) ranges using dilution antimicrobial
      susceptibility testing methods for bacterial isolates from aquatic animal
      species. QC ranges were established for Escherichia coli ATCC 25922 and Aeromonas
      salmonicida subsp. salmonicida ATCC 33658 when testing at 22, 28 and 35 degrees C
      (E. coli only) for 10 different antimicrobial agents (ampicillin, enrofloxacin,
      erythromycin, florfenicol, flumequine, gentamicin, ormetoprim/sulfadimethoxine,
      oxolinic acid, oxytetracycline and trimethoprim/sulfamethoxazole). Minimum
      inhibitory concentration (MIC) QC ranges were determined using dry- and frozen
      form 96-well plates and cation-adjusted Mueller-Hinton broth. These QC ranges
      were accepted by the CLSI/NCCLS Subcommittee on Veterinary Antimicrobial
      Susceptibility Testing in January 2004. This broth microdilution testing method
      represents the first standardized method for determining MICs of bacterial
      isolates whose preferred growth temperatures are below 35 degrees C. Methods and
      QC ranges defined in this study will enable aquatic animal disease researchers to
      reliably compare quantitative susceptibility testing data between laboratories,
      and will be used to ensure both precision and inter-laboratory harmonization.

PMID- 15997820
TI  - Physiological responses to acute temperature increase in European eels Anguilla
      anguilla infected with Anguillicola crassus.
AB  - The swimbladder parasite, Anguillicola crassus has infected, and spread rapidly,
      through European eel Anguilla anguilla (L.) populations over the past 20 to 25
      yr. Our aim in the present studies was to elucidate whether the presence of A.
      crassus in these eels alters their rapid physiological responses to an acute
      temperature increase, compared to the response of uninfected fish. Both infected
      and uninfected fish showed significant increases in plasma cortisol after 2 h at
      a raised environmental temperature with increased plasma glucose after 6 h.
      However, infected eels exhibited a slight lag in glucose mobilisation, which may
      be due to the metabolic cost of harbouring a sanguiverous parasite. Both infected
      and uninfected fish showed a significant increase in haematocrit after 6 h of
      temperature elevation, but only uninfected fish exhibited a significant increase
      in haemoglobin at this point. However, there were no significant changes in mean
      erythrocyte haemoglobin concentration in either group. Our results suggest that
      acute temperature increase alone is unlikely to cause significant mortality of A.
      crassus-infected European eels; however, the effects of chronic increases in
      temperature in combination with other factors such as toxicants and hypoxia
      requires examination.

PMID- 15997821
TI  - Histology, ultrastructure and prevalence of Henneguya piaractus (Myxosporea)
      infecting the gills of Piaractus mesopotamicus (Characidae) cultivated in Brazil.
AB  - The histopathological and ultrastructural characteristics of Henneguya piaractus,
      a parasite of the gill lamellae of Piaractus mesopotamicus, are reported here.
      Histological analysis showed that the plasmodia were of the intralamellar type.
      The development of the plasmodia resulted in marked dilatation of the infected
      lamellae, with the neighbouring lamellae being displaced laterally. Discreet
      epithelial hyperplasia was observed, but there was no inflammatory reaction.
      Ultrastructural analysis showed that the plasmodium had a single thin wall that
      was in direct contact with the host cells. Pinocytic canals and points of
      phagocytosis were observed in the wall. The prevalence of the parasite varied
      according to host size, with the lowest prevalence occurring in hosts up to 10 cm
      long.

PMID- 15997822
TI  - Compressed vertebrae in Atlantic salmon Salmo salar: evidence for metaplastic
      chondrogenesis as a skeletogenic response late in ontogeny.
AB  - Anterior/posterior (a/p) compression of the vertebral column, referred to as
      'short tails', is a recurring event in farmed Atlantic salmon. Like other
      skeletal deformities, the problem usually becomes evident in a late life phase,
      too late for preventive measures, making it difficult to understand the aetiology
      of the disease. We use structural, radiological, histological, and mineral
      analyses to study 'short tail' adult salmon and to demonstrate that the study of
      adult fish can provide important insights into earlier developmental processes.
      'Short tails' display a/p compressed vertebrae throughout the spine, except for
      the first post-cranial vertebrae. The vertebral number is unaltered, but the
      intervertebral space is reduced and the vertebrae are shorter. Compressed
      vertebrae are characterized by an unchanged central part, altered vertebral end
      plates (straight instead of funnel-shaped), an atypical inward bending of the
      vertebral edges, and structural alterations in the intervertebral tissue. The
      spongiosa is unaffected. The growth zones of adjacent vertebrae fuse and blend
      towards the intervertebral space into chondrogenic tissue. This tissue produces
      different types of cartilage, replacing the notochord. The correspondence in
      location of intervertebral cartilage and deformed vertebral end plates, and the
      clearly delimited, unaltered, central vertebral parts suggest that the a/p
      compression of vertebral bodies is a late developmental disorder that may be
      related to a metaplastic shift of osteogenic tissue into chondrogenic tissue in
      the vertebral growth zone. Given the lack of evidence for infections, metabolic
      disorders and/or genetic disorders, we propose that an altered mechanical load
      could have caused the transformation of the bone growth zones and the concomitant
      replacement of the intervertebral (notochord) tissue by cartilaginous tissues in
      the 'short tails' studied here. This hypothesis is supported by the role that
      notochord cells are known to play in spine development and in maintaining the
      structure of the intervertebral disk.

PMID- 15997823
TI  - Chytrid fungus parasitizing the wild amphibian Leptodactylus ocellatus (Anura:
      Leptodactylidae) in Argentina.
AB  - The present contribution is the first report of parasitosis by a chytrid fungus
      in wild anuran amphibians in Argentina, as well as the first case of amphibian
      mortality documented to date in Argentina. We report the presence of the chytrid
      fungus in dead adult Leptodactylus ocellatus. It has been suggested that
      chytridiomycosis is the main cause of death in several amphibian populations
      worldwide. Our study demonstrates that chytridiomycosis afflicts L. ocellatus, a
      common widespread amphibian species, and is the first report of chytridiomycosis
      in the Argentinian lowlands. The occurrence at this latitude would indicate an
      extended distribution of this fungus in wildlife populations. It is also the
      first report of amphibian mortality due to chytrid fungus in our country. It is
      noteworthy that the site of collection is situated very close to sea level in a
      temperate climate zone and that this represents the southern most record for
      South American wild amphibians.

PMID- 15997824
TI  - Epidemiology of bitter crab disease (Hematodinium sp.) in snow crabs Chionoecetes
      opilio from Newfoundland, Canada.
AB  - The parasitic dinoflagellate Hematodinium sp. causes a condition known as bitter
      crab disease (BCD) in snow crabs Chionoecetes opilio and Tanner crabs C. bairdi.
      As the name of the condition implies, crabs infected with BCD are unmarketable
      due to their bitter flavor. We surveyed the distribution of BCD in 3 regions
      within the snow crab fishery of Newfoundland from 1997 to 2003. Over time, the
      disease has become firmly established in Conception and Bonavista Bays and
      persists at low levels on the Avalon fishing grounds. An epizootic occurred
      within Bonavista and Conception Bays in 1999 and persisted in Conception Bay in
      2000, reaching prevalences of over 2% to 9% in trapped and trawled male crabs and
      from 19 to 26% in trawled and trapped female crabs, respectively. Infections were
      highest in females and small males, i.e. the unfished and pre-recruit portions of
      the fishery. In a mortality study, all of the naturally infected crabs died and
      50% of the experimentally inoculated crabs died. Patterns in the molting cycle
      and prevalence of infection indicate that transmission occurs during the post
      molt condition, and that overt infections probably develop 2 to 4 mo later with
      mortalities occurring at least 3 to 4 mo thereafter. The hydrography of this bay
      may have contributed to the epizootic as infections were centered within the
      deeper confines of the bay. Analysis of various abiotic factors uncovered a
      significant positive association between prevalence, depth and mud/sand
      substrates; the nature of this relationship was not apparent but may be related
      to diet or alternate hosts. Lastly, given the increase in BCD in snow crabs in
      Newfoundland, we recommend that fishery management programs for Chionoecetes
      fisheries employ non-selective gear to monitor for Hematodinium infections in
      female and juvenile crabs because these under-sampled members of the population
      may forewarn of impending recruitment declines that might otherwise remain
      unexplained.

PMID- 15997825
TI  - Macroparasites in stranded and bycaught harbour porpoises from German and
      Norwegian waters.
AB  - Parasitological investigations were carried out on harbour porpoises Phocoena
      phocoena originating from 3 different areas: the German North Sea (28), the
      German Baltic (18) and Norwegian waters (22). The individuals were bycaught in
      gill-nets or found stranded during the period 1997 to 2000. A total of 7 species
      of parasites was identified from the investigated organs. These originated mainly
      from the respiratory tract and comprised 1 ascaridoid nematode (Anisakis
      simplex), 4 pseudaliid nematodes (Pseudalius inflexus, Torynurus convolutus,
      Halocercus invaginatus, Stenurus minor) and 2 trematodes (Campula oblonga,
      Pholeter gastrophilus). This is the first geographic record of H. invaginatus
      from German waters. Differences were found in the severity of the parasitic
      infection between stranded and bycaught animals as well as between porpoises from
      different areas. A correlation was shown between parasitic infection and observed
      lesions.

PMID- 15997826
TI  - Piperidine-containing histamine H3 receptor antagonists of the carbamate series:
      the alkyl derivatives.
AB  - A series of N-alkyl urethanes, potential histamine H3 receptor antagonists, was
      prepared. Carbamate derivatives were synthesized from appropriate isocyanates and
      N-piperidinoalkan-1-ols. The novel compounds were evaluated for histamine H3
      receptor activity in vitro on the guinea pig ileum. Some selected compounds were
      tested in vivo after p.o. application to mice and in vitro for selectivity
      towards other histamine receptors (H1, H2) in functional assays in the guinea
      pig. The most potent H3 receptor antagonist in vitro was compound 14 (pA2 = 7.2).
      Compound 14 was equipotent at M3 receptors and lacked H3 receptor activity in
      vivo. Predictions of octanol-water partition coefficient (Pallas) and metabolic
      fate (MetabolExpert, METEOR) were used to explore potential reasons for this
      absence of in vivo activity.

PMID- 15997827
TI  - Microwave-assisted solvent-free synthesis of 3-[(4-substituted piperazin-1
      yl)alkyl] imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones as serotonin3 (5-HT3)
      receptor antagonists.
AB  - A series of novel 3-[(4-substituted piperazin-1-yl)alkyl]imidazo[2,1
      b][1,3]benzothiazol-2(3H)-ones were prepared by microwave irradiation using
      alumina as solid support and also by a conventional method. The compounds were
      characterized by spectral data and the purity was ascertained by microanalysis.
      The synthesized compounds were evaluated for 5-hydroxytryptamine3 antagonisms in
      a longitudinal muscle-myenteric plexus preparation from guinea pig ileum against
      the 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine. Among the test
      compounds, 3-[2-(4-methylpiperazin-1-yl)ethyl]imidazo[2,1-b][1,3]benzothiazol
      2(3H)-one (3b) showed most favorable 5-hydroxytryptamine3 antagonism (pA2 6.7) in
      the isolated guinea pig ileum.

PMID- 15997828
TI  - [Protected mercaptoalkylpyrimidinones: synthesis and test for immunostimulating
      activity].
AB  - Protected mercaptoalkylpyrimidinones: synthesis and test for immunostimulating
      activity 3-Hydroxyalkyl-pyrimidine 1 reacts with phosphoroxychloride and
      thioglycolic acid or thiourea to yield pyrimidin-3-ylalkylthioacetic acids 3 or
      pyrimidin-3-ylalkylthiouroniumsalts 5 respectively. Some of the pyrimidines 3 and
      5 showed immunomodulatory activity.

PMID- 15997829
TI  - HPLC determination of telmisartan in human plasma and its application to a
      pharmacokinetic study.
AB  - A sensitive, simple, and accurate HPLC method was developed for the assay of
      telmisartan in human plasma. Using naproxen as internal standard, the assay
      involved liquid-liquid extraction of the compound from acidified plasma into
      organic solvent and reversed-phase chromatography with fluorescence detection.
      The assay was shown to be linear from 0.5 to 1000 ng/mL. In 24 healthy
      volunteers, the plasma concentrations of the drug were determined after a single
      oral dose of 160 mg.

PMID- 15997830
TI  - Determination of lornoxicam in pharmaceutical preparations by zero and first
      order derivative UV spectrophotometric methods.
AB  - Zero and first order derivative UV spectrophotometric methods were developed for
      the analysis of lornoxicam (LOR). The solutions of the standards and
      pharmaceutical samples were prepared in 0.05 N NaOH. Absorbances of LOR were
      measured at 376 nm for the zero order by measuring height of peak from zero and
      at 281 and 302 nm for the first order derivative spectrophotometric method by
      measuring peak to peak height. The linearity ranges were found to be 0.5-35
      microg/mL for the zero order and 0.2-75 microg/mL for the first order derivative
      UV spectrophotometric method. The methods were validated and applied to the
      determination of LOR in pharmaceutical preparations (tablet and injectable, both
      containing 8 mg LOR). It was concluded that the methods developed were accurate,
      sensitive, precise, robust, rugged and useful for the quality control of LOR in
      pharmaceutical preparations.

PMID- 15997831
TI  - Photoreactivity of biologically active compounds. XVII. Influence of solvent
      interactions on spectroscopic properties and photostability of primaquine.
AB  - The influence of solvent interactions on absorption properties, fluorescence
      properties (emission spectra and quantum yields) and relative photochemical
      degradation rates of primaquine has been investigated, in order to evaluate
      photochemical reaction mechanisms and chemical properties of the compound. The
      first absorption band (n - pi*) of primaquine is only slightly dependent on
      properties of the solvent, which can be ascribed to a strong, intramolecular
      hydrogen bond between the quinoline N and amine group in the ground state (S0).
      Amphiprotic solvents with predominant acidic properties (water and methanol) will
      to some extent stabilize the molecule and initiate hypsochromic shifts of the
      absorption band by protic interactions, while the other solvents (amphiprotic,
      basic and neutral) influence the absorption spectrum by general solvent effects
      only. The excited singlet (S1*) state of primaquine interacts more efficiently
      with the surrounding solvents than the S0 state, as evaluated by the Stokes
      shifts. The pKa value of the quinoline N is likely to increase in the S1* state,
      which is important for the observed protic interactions with amphiprotic solvents
      of predominant acidity. Specific solvent effects are highly important for the
      efficiency of the fluorescence (fluorescence quantum yields; phi f). The
      fluorescence is quenched by amphiprotic solvents, likely due to a rupture of the
      intramolecular bond and protonation of the quinolone N, and enhanced by polar,
      non-protic (basic) solvents, probably by stabilization of the delta
      intramolecular hydrogen bond. The observed photochemical degradation rates of
      primaquine in amphiprotic media are positively correlated with phi f, indicating
      that the photochemical degradation of primaquine is dependent on intramolecular
      hydrogen bonding and non protonated lone-pair electrons at the quinoline N. The
      intramolecular ring-formation with a subsequent increased lipophilic character
      and (lack of) interactions with the surroundings, are important factors for
      biological behavior as well as pharmaceutical properties of primaquine. Knowledge
      about solvent interactions with primaquine in the S0 and S1* states is essential
      for the proceeding evaluation of photostability and phototoxicity of the drug.

PMID- 15997832
TI  - Optimization and characterization of chitosan-coated alginate microcapsules
      containing albumin.
AB  - In order to obtain small microcapsules with high protein encapsulation efficiency
      and extended release characteristics various processing factors were studied.
      Bovine serum albumin-loaded alginate microcapsules were prepared by an emulsion
      method and further incubated in chitosan. Many process factors were tested
      including the concentration and molecular weight of alginate, the concentration
      and pH of chitosan, and surfactants, etc. Microcapsules were achieved with
      diameters less than 2 microm, high encapsulation efficiency (> 80%) and high
      loading rate (> 10% w/w). The results also showed that the initial BSA amount of
      20%-30% loaded alginate microcapsules coated with 0.2%-0.5% chitosan solutions at
      pH 4 by the two-stage procedure present the best sustained releasing
      characteristics.

PMID- 15997833
TI  - Melanin potentiates kanamycin-induced inhibition of collagen biosynthesis in
      human skin fibroblasts.
AB  - Ototoxicity is one of the well known side effects of kanamycin. The mechanism
      underlying the organ specificity of the side effect is not understood. Since many
      pharmacologic agents are known to form complexes with melanin and melanin is an
      abundant constituent of the inner ear, we investigated whether kanamycin
      interacts with melanin and how this process affects biosynthesis of collagen in
      cultured human skin fibroblasts. We found that kanamycin forms complexes with
      melanin. The amount of kanamycin bound to melanin increases with increase of
      initial drug concentration. The Scatchard plot analysis of the drug binding to
      melanin has shown that at least two classes of independent binding sites are
      implicated in the kanamycin-melanin complex formation: strong binding sites with
      the association constant K1 - 3 x 10(5) M(-1), and the weak binding sites with K2
      - 4 x 10(3) M(-1). The number of total binding sites (n1 + n2) was calculated as
      about 0.64 micromol kanamycin per 1 mg melanin. We found that kanamycin induced
      inhibition of collagen and DNA biosynthesis (IC50 - 5 microM). Melanin at 100
      microg/ml produced about 25% inhibition of DNA synthesis, but it had no effect on
      collagen biosynthesis in cultured fibroblasts. However, the addition of melanin
      (100 microg/ml) to kanamycin-treated cells (5 microM) augmented the inhibitory
      action of kanamycin on collagen and DNA biosynthesis. We have suggested that IGF
      I receptor expression, involved in cell growth and collagen metabolism, may be
      one of the targets for kanamycin-induced inhibition of these processes. As shown
      by Western immunoblot analysis melanin augmented kanamycin-induced decrease in
      the expression of IGF-I receptor as well MAP kinases expression: ERK1 and ERK2.
      The obtained results demonstrate that melanin potentiates the inhibitory effect
      of kanamycin on IGF-I receptor-dependent signaling pathway in cultured
      fibroblasts. The data suggest a potential mechanism for the organ specificity of
      kanamycin-induced hearing loss in patients which may result from melanin-induced
      augmentation of the inhibitory effects of kanamycin on collagen and DNA
      biosynthesis.

PMID- 15997834
TI  - Luteolin induces vasorelaxion in rat thoracic aorta via calcium and potassium
      channels.
AB  - The aims of the present study were to investigate the vasoactive effects of
      luteolin and its mechanisms of action on the rat thoracic aorta. Luteolin (4.5-36
      micromol/L) caused a concentration-dependent relaxation of endothelium-intact or
      endothelium-denuded aortic rings precontracted with phenylephrine (PE, 10(-6)
      mol/L) or a high level of K+ (6 x 10(-2) mol/L). Luteolin induced a shift of the
      PE concentration-response curve to the right and downward. L-NAME and propranolol
      did not influence the vascular effect of luteolin. However, 5-hydroxydecanoate,
      tetraethylammonium, BaCl2 and 4-aminopyridine significantly attenuated the
      vasorelaxant effect of luteolin. In Ca2+ -free medium, medium with graded
      concentrations of Ca2+, or K+ -free solution, luteolin reduced PE-induced
      contraction. It is concluded that luteolin induces endothelium-independent
      relaxation in rat thoracic aorta. The mechanism involves the inhibition of
      sarcolemmal Ca2+ channels, release from intracellular Ca2+ stores and activation
      of K+ channels.

PMID- 15997835
TI  - Human cancer cells exhibit in vitro individual receptiveness towards different
      mistletoe extracts.
AB  - In vitro cytotoxic effects of three aqueous mistletoe extracts on cell physiology
      against different human tumor cell lines and primary cancer cells were
      investigated in order to compare the receptiveness of different cancer cells
      against different mistletoe products. Therefore cell proliferation (BrdU
      incorporation assay), mitochondrial activity (MTT-testing) and necrotic cell
      toxicity (LDH assay) were assayed over serial dilutions of the test products.
      Data obtained with HELA-S3, MOLT-4, MFM-223, COR-L51, KPL-1 and VM-CUB1 tumor
      cell lines and Iscador M (20 mg/ml), Iscador Q (20 mg/ml) and Abnobaviscum
      Fraxini -2 (20 mg/ml) indicated significant growth-inhibition of all cell lines,
      but also different cell susceptibilities against the different extracts. These
      variations were not only monitored on established cell lines but also on primary
      mamma carcinoma cells from surgical resectates. Concerning cell proliferation and
      mitochondrial activity Abnobaviscum Fraxini exhibits stronger inhibitory effects
      compared to products from the Iscador series. In case the evaluation was
      standardized on the active contents of VAA-I within the different products, the
      Iscador extracts possess higher cytotoxic activity. Pure viscotoxins and
      mistletoe lectins exhibited less effects than the extracts. The simultaneous
      presence of pure mistletoe lectins and mistletoe polysaccharides diminished the
      VAA-mediated cytotoxic effects. The presence of fetal calf serum (FCS) in
      cultivation media during in vitro testing diminished the cytotoxic effects of
      mistletoe extracts. It was shown that in vivo application of mistletoe
      preparations led to the formation of antibodies against unknown compounds of the
      extracts, diminishing the cytotoxic effect.

PMID- 15997836
TI  - New prenylated benzoic acid derivatives of Piper hispidum.
AB  - Three new 4-hydroxy-benzoic acid derivatives, 4-methoxy-3,5-bis-(3-hydroxy-3
      methyl-1-butenyl)benzoate, 3-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3
      dihydrobenzofuran-5-carboxylic acid, and 3-hydroxy-2-(1-hydroxy-1-methylethyl)
      2,3-dihydrobenzofuran-5-carboxylic acid methyl ester together with eight known
      compounds, have been isolated from the stems of Piper hispidum. Their structures
      were elucidated by a detailed spectroscopic analysis. In addition, the
      cytotoxicity of seven isolated compounds has been evaluated, revealing a moderate
      activity for three derivatives of dillapiole.

PMID- 15997837
TI  - Cytotoxic ent-kaurane diterpenoids from Isodon weisiensis C. Y. Wu.
AB  - A new ent-kaurane diterpenoid, weisiensin B (1), was isolated from the leaves of
      Isodon weisiensis C. Y. Wu, along with four known ones, kamebanin (2),
      kamebacetal A (3), macrocalyxin D (4) and excisanin D (5). Their structures were
      determined by spectroscopic means. Compound 1-4 showed significant cytotoxic
      activity against Bel-7402 and HO-8910 cells.

PMID- 15997838
TI  - Diterpene glycosides from Aster homochlamydeus.
AB  - A new diterpene glycoside 1 was isolated from the whole plant of Aster
      homochlamydeus Hand-mazz (Compositae), along with four known diterpene glycosides
      2-5. Their structures were elucidated by spectroscopic methods, MS, IR, NMR and X
      raycrystallographic analyisis. Antibacterial activity of compounds 1-5 was
      observed.

PMID- 15997839
TI  - Steroids from Saussurea ussuriensis.
AB  - One novel and seven known steroids were isolated from the alcohol extract of the
      whole plant of Saussurea ussuriensis. The structure of the new compound was
      elucidated as stigmast-5-en-3beta,7alpha,22-triol (1) by spectroscopic methods
      including intensive 2D NMR techniques (H1-H1 COSY, gHSQC, gHMBC) and HR-SI-MS and
      the known compounds were identified on the basis of comparing their NMR data with
      those of corresponding compounds in the literature.

PMID- 15997840
TI  - [Fritz hauschild (1908-1974) and drug research in the 'German Democratic
      Republic' (GDR)].
AB  - The chemist and pharmacologist Fritz Hauschild developed the sympathomimetic
      agent Pervitin (metamphetamin) in the 1930s. Not only because of the abuse of the
      stimulant during the Second World War ("pilot's chocolate") it is one of the most
      controversial substances in drug history. Nearly forgotten are Hauschild's
      contributions to build up the drug system in the GDR. Although he was a convinced
      communist, the skilful pharmacologist gave very early warning of the imminent
      lack of innovation in the GDR pharmaceutical industry. A letter which he
      addressed to the Minister of Health, Max Sefrin (born 1913), did not lack
      explicitness.

PMID- 15997841
TI  - Cationic niosomes as gene carriers: preparation and cellular uptake in vitro.
AB  - Cationic niosomes of sorbitan monoesters were prepared using film hydration
      method and tested for their effect on delivery of antisense oligonucleotides
      (OND) in a COS-7 cell line. These formulations showed positive results on
      cellular uptake of antisense oligonucleotides. Especially, cationic niosomes of
      Span 40 and 60 have a more significant effect.

PMID- 15997842
TI  - Enhanced oral bioavailability of breviscapine after encapsulation in a liposomal
      formulation.
AB  - This report firstly describes the pharmacokinetic study of liposomal breviscapine
      (LB) after oral administration in rats. The mean Cmax and AUC(0-->t) of LB were
      3.3 and 3.1-fold higher than those of breviscapine solution (BS). The oral
      absorption of breviscapine was significantly increased after encapsulation in the
      liposomal formulation.

PMID- 15997843
TI  - Study on the role of hepatic first-pass elimination in the low oral
      bioavailability of scutellarin in rats.
AB  - In the present study, we compared the systemic exposure of scutellarin following
      intraportal with intravenous administration to understand the contribution of
      presystemic hepatic elimination to the low oral bioavailability. Results showed
      that the hepatic first-pass elimination of scutellarin played an insignificant
      role in the presystemic elimination of orally administered scutellarin. Moreover,
      our results suggested that the site of first pass extraction was not the liver,
      but the gastrointestinal tract.

PMID- 15997844
TI  - Effect of aqueous extract of Pterocarpus marsupium wood on alloxan-induced
      diabetic rats.
AB  - An aqueous extract of Pterocarpus marsupium wood was screened for hypoglycemic
      activity on alloxan-induced diabetic rats. During both acute and sub-acute tests,
      the water extract, at an oral dose of 250 mg/kg, showed statistically significant
      hypoglycemic activity.

PMID- 15997845
TI  - Secondary metabolites in in vitro cultured plants of the genus Drosera.
AB  - Extracts from plantlets of different species of the genus Drosera, grown as in
      vitro cultures, were evaluated for the level of phenolic secondary metabolites
      from the group of naphthoquinones and flavonols. The profiles of natural products
      in the extracts obtained from different species were monitored by HPLC with UV
      detection at 260 and 330 nm. On the basis of the data obtained, Drosera binata,
      the species with the highest amount of plumbagin, was selected for further
      studies. The most effective method of extraction of quinones was established and
      the composition of phenolic secondary metabolites in the tissues was determined.
      For the identification of phenolic compounds, HPLC-UV and HPLC-ESI/MS were
      applied.

PMID- 15997846
TI  - Identification and quantitative determination of eudesmane-type acids from the
      essential oil of Dittrichia viscosa sp. viscosa using 13C-NMR spectroscopy.
AB  - A procedure that allows the identification and quantitative determination of
      eudesmane-type acids in the acidic part of the essential oil of Dittrichia
      viscosa sp. viscosa is described. The method involves the computer-aided analysis
      of the 13C-NMR spectrum of the mixture without the requirement of previous
      separation or derivatisation. The quantitative procedure was verified with costic
      acid standard and applied to three other acids which possess the same eudesmane
      framework.

PMID- 15997847
TI  - Isolation and purification of closely related citrus limonoid glucosides by flash
      chromatography.
AB  - Several citrus limonoid glycosides have proved to be particularly difficult to
      purify using conventional techniques. A reversed-phase flash chromatographic
      technique has been developed for the separation and isolation of the closely
      related limonoid glucosides, nomilin 17-beta-D-glucopyranoside and nomilinic acid
      17-beta-D-glucopyranoside, with confirmation of their identities by electrospray
      ionisation mass spectrometry. Furthermore, the semi-purification of the mixture
      of glucosides enriched with flavanone glucosides such as naringin, narirutin and
      other limonoid glucosides was obtained. The closely eluting glucosides were
      successfully separated to achieve a good yield and purity of 93%.

PMID- 15997848
TI  - Quantitative determination of enhydrin in leaf rinse extracts and in glandular
      trichomes of Smallanthus sonchifolius (Asteraceae) by reversed-phase high
      performance liquid chromatography.
AB  - A simple, reliable and rapid reversed-phase HPLC-PAD procedure for the
      characterisation and quantitative determination of the anti-diabetic
      sesquiterpene lactone enhydrin (1) from Smallanthus sonchifolius (yacon) has been
      evaluated and validated. The approach focused on the analysis of various leaf
      rinse extracts, as well as the glandular trichomes of intact leaves, in which 1
      was the major compound detected. The best sample preparation of a rinse extract
      yielded 0.67 mg/mL of 1, whilst a rapid rinse of a small piece of one dried leaf
      gave 0.09 mg/mL of 1; the highest concentration obtained from a glandular extract
      was 0.07 mg/mL. The dried leaves of S. sonchifolius were found to contain a total
      of 0.97% of 1.

PMID- 15997849
TI  - On-line identification of the bioactive compounds from Blumea gariepina by HPLC
      UV-MS and HPLC-UV-NMR, combined with HPLC-micro-fractionation.
AB  - The dichloromethane extract of the aerial parts of Blumea gariepina (Asteraceae)
      was shown to be active against the phytopathogenic fungus Cladosporium
      cucumerinum and to inhibit acetylcholinesterase. In order rapidly to identify the
      active principles, the crude extract was analysed by on-flow HPLC-1H-NMR. HPLC
      micro-fractionation was performed and all peaks collected were submitted to
      assays against C. cucumerinum and acetylcholinesterase. By this means, the
      biological activities could be efficiently associated with selected HPLC peaks.
      Complementary on-line structural data for all peaks of interest in the crude
      extract were obtained from HPLC-MS and from HPLC-UV with post-column addition of
      UV shift reagents. This chemical screening strategy with integrated bioassays
      permitted the on-line identification of a number of constituents and gave useful
      information for an efficient isolation procedure.

PMID- 15997850
TI  - Quantification and characterisation of cyclo-oxygenase and lipid peroxidation
      inhibitory anthocyanins in fruits of Amelanchier.
AB  - The levels of bioactive anthocyanins in the fruits of Amelanchier alnifolia, A.
      arborea and A. canadensis have been determined by HPLC. Cyanidin 3-galactoside
      (1) was present in the fresh fruit of the three species at concentrations of 155,
      390 and 165 mg/100 g, respectively. Cyanidin 3-glucoside (2) was present only in
      A. alnifolia and A. canadensis at concentrations of 54 and 48 mg/100 g,
      respectively. The anthocyanins were confirmed by LC-ESI/MS and NMR studies. At
      100 ppm, anthocyanin mixtures from the three species inhibited cyclo-oxygenase
      (COX)-1 and -2 enzymes at 66 and 67%, 60 and 72%, and 51 and 76%, respectively.
      The positive controls used in the COX assays were aspirin, Celebrex and Vioxx at
      180, 1.67 and 1.67 ppm, respectively, and showed 74 and 69%, 5 and 82% and 0 and
      85% COX-1 and COX-2 inhibition, respectively. Anthocyanins 1 and 2 and cyanidin
      (3) inhibited COX-1 enzyme 50.5, 45.62 and 96.36%, respectively, at 100 ppm,
      whereas COX-2 inhibition was the highest for 3 at 75%. In the lipid peroxidation
      inhibitory assay, anthocyanin mixtures at 10 ppm from the three species showed
      activities of 72, 73 and 68%, respectively, compared with 89, 87 and 98% for
      commercial anti-oxidants butylated hydoxyanisole, butylated hydroxytoluene, and
      tert-butylhydroxyquinone at 1.67, 2.2 and 1.67 ppm, respectively. At 10 ppm,
      compounds 1-3 inhibited lipid peroxidation by 70, 75 and 78%, respectively.

PMID- 15997851
TI  - Identification of ginsenosides in roots of Panax ginseng by HPLC-APCI/MS.
AB  - A new HPLC-APCI/MS method for the identification of ginsenosides has been
      developed. The analyses were performed on a reversed-phase C18 column using a
      binary eluent (acetonitrile and water) under gradient conditions. Although APCI
      is a high-temperature evaporative process, HPLC-APCI/MS could effectively
      identify thermo-labile ginsenosides. The [M-H]- ions and the thermal degradation
      ions of ginsenosides could be clearly observed under negative and positive ion
      conditions, respectively, and these were used to identify the molecular masses,
      the aglycone structures and the sugar groups of ginsenosides. APCI/MS can provide
      more explicit information than ESI/MS for identifying and distinguishing
      ginsenosides. Using the HPLC-APCI/MS method, 35 ginsenosides were identified in
      Panax ginseng.

PMID- 15997852
TI  - Chromatographic analysis of carotenol fatty acid esters in Physalis alkekengi and
      Hippophae rhamnoides.
AB  - The carotenol fatty acid esters of two potentially valuable sources of plant
      carotenoids, sepals of Physalis alkekengi (Chinese lantern) and fruits of
      Hippophae rhamnoides (sea buckthorn), were separated by column chromatography and
      identified by HPLC-DAD and HPLC-MS. A chemical and an enzymatic hydrolysis were
      employed to identify the parent carotenoids and to remove the lipid components.
      Zeaxanthin and beta-cryptoxanthin esters represented the main fraction in P.
      alkekengi sepals and an important one in H. rhamnoides fruits. Beta-Cryptoxanthin
      palmitate and zeaxanthin dipalmitate were identified as major compounds in both
      plants. In P. alkekengi, the carotenoids were mainly (> 90%) esterified with
      palmitic acid, and a high proportion (> 80%) of saturated medium chain fatty
      acids was found (by GC-MS) in the total lipid extract. Although the total lipid
      extract of H. rhamnoides contained significant amounts of unsaturated fatty
      acids, especially oleic and palmitoleic acids, the xanthophylls were mainly
      esterified with saturated fatty acids. The oleoresins of both species represent
      potential sources of carotenoid esters and can be used as food additives,
      cosmetic ingredients or nutraceuticals.

PMID- 15997853
TI  - Determination of aflatoxins in medicinal herbs by HPLC. An efficient method for
      routine analysis.
AB  - A fast and easy to perform method for the routine determination of aflatoxins in
      medicinal herbs was developed. The described method involves a single-step
      extraction with a non-chlorinated solvent, an immunoaffinity clean-up and HPLC
      with fluorescence detection. Whilst assays with naturally contaminated and with
      spiked samples of several herbs showed that the recoveries were somewhat low and
      dependent on the kind of sample and the degree of grinding, the intra-batch
      reproducibility was good, allowing a reliable quantitation by the standard
      addition method. Good linearity, repeatability and accuracy were demonstrated in
      assays involving several medicinal herbs. The limit of quantitation was of the
      order of 0.05-0.1 ng/g, being dependent of the species analysed, and the method
      required no tedious concentration or back-extraction steps.

PMID- 15997854
TI  - Differentiation of Cirsium japonicum and C. setosum by TLC and HPLC-MS.
AB  - The Chinese Pharmacopoeia indicates the use of field thistle (Cirsium setosum)
      and Japanese field thistle (C. japonicum) in the treatment of bleeding and
      inflammation. In the absence of an analytical method for the differentiation and
      analysis of these two species, TLC and HPLC-MS methods have been developed for
      this purpose. Both species could be readily distinguished by their flavonoid
      pattern as revealed by TLC on silica gel layers eluted with ethyl acetate:formic
      acid:acetic acid:water. The quantitative determination of four flavonoids, namely
      hispidulin-7-neohesperidoside, linarin, pectolinarin and luteolin, was possible
      using HPLC. Their optimum separation was achieved on a C12 column eluted with
      water and 0.025% trifluoroacetic acid in acetonitrile. HPLC-MS experiments were
      performed to confirm peak identity. In samples of C. japonicum, pectolinarin was
      the major flavonoid (0.32-2.00%), followed by linarin, hispidulin-7
      neohesperidoside and luteolin; the total flavonoid content varied from 0.81 to
      3.67%. In C. setosum only one flavonoid (linarin; 1.36-2.83%) was assignable. The
      HPLC method was validated for linearity, limit of detection (< or = 1.7 ng on
      column), peak purity, repeatability (< or = 2.3%) and accuracy (recovery rates of
      spiked samples were between 99.2 and 101.6%).

PMID- 15997855
TI  - Flavonoids from the leaves of Cyclanthera pedata: two new malonyl derivatives.
AB  - Reversed-phase HPLC coupled with electrospray MS has been used for the
      simultaneous separation and determination of flavonoid metabolites in leaves of
      Cyclanthera pedata, an edible Peruvian plant mainly used in South America for its
      anti-inflammatory, hypoglycaemic and hypocholesterolaemic properties. The
      flavonoid content of the leaves of C. pedata was compared qualitatively and
      quantitatively with that of the fruits. The isolation and structural
      characterisation by MS and NMR of two new minor components of the fruits, namely,
      6-C-fucopyranosyl-(3-malonyl)-chrysin and 6-C-fucopyranosyl-(4-malonyl)-chrysin,
      are described.

PMID- 15997856
TI  - Superheated water chromatography-nuclear magnetic resonance spectroscopy of kava
      lactones.
AB  - Three kava lactone constituents of Piper methysticum, namely, kawain, methysticin
      and desmethoxyyangonin, have been separated and identified by reversed-phase HPLC
      using superheated deuterium oxide as the mobile phase and on-line 1H-NMR
      detection. The method avoids the use of organic solvents in the mobile phase and
      hence interferences in the NMR analysis are minimised.

PMID- 15997857
TI  - Analysis of aristolochic acids and analogues in medicinal plants and their
      commercial products by HPLC-PAD-ESI/MS.
AB  - An HPLC-UV-MS method for the analysis of aristolochic acids A, B, C and D, 7-OH
      aristolochic acid A, and aristolic acid in a number of plant materials and their
      commercial products has been developed. HPLC with photodiode array detection and
      electrospray ionisation-MS in the selected ion monitoring mode allowed the
      identification of the target compounds and increased the selectivity of complex
      analyses such as those associated with multi-botanical preparations. The
      presented method was used to analyse 10 plant samples and six commercial products
      that possibly contained aristolochic acids. The resulting chromatographic
      profiles of the samples were significantly different from each other, and the
      method was directly transferred to HPLC-MS, which was used to confirm the
      presence of the six aristolochic acids mentioned above.

PMID- 15997858
TI  - Current awareness in phytochemical analysis.

PMID- 15997859
TI  - Four more years.

PMID- 15997860
TI  - Forgotten not gone.

PMID- 15997861
TI  - Bete noire. Interview by Lynne Friedli.

PMID- 15997862
TI  - Unleashing creativity.

PMID- 15997863
TI  - Polluting their minds.

PMID- 15997864
TI  - Cash in their hands.

PMID- 15997865
TI  - A measure of concerns.

PMID- 15997866
TI  - Why shouldn't we choose?

PMID- 15997867
TI  - This life. Interview by Suzy Johnston.

PMID- 15997868
TI  - A study of the factors responsible for the development of allergic diseases in
      early life.
AB  - In order to analyze the determinants involved in the development of allergic
      diseases early in infancy, we examined the environmental and genetic factors that
      might affect the induction of such diseases during infancy, using a
      questionnaire. Maternal pharyngitis during pregnancy was significantly related to
      the development of atopic dermatitis in their progeny. Moreover, the frequency of
      the maternal infection was associated with a significantly increased risk of
      allergy in their infants. The prevalence of post-delivery maternal allergy was
      positively linked to the allergic symptoms in their children while the likelihood
      of bearing allergic children was related to the numbers of allergic individuals
      within their family. These results suggested that pre- and post-natal maternal
      factors and any genetic predisposition might modify the development of allergy in
      infancy.

PMID- 15997869
TI  - Asthma prescribing practices of government and private doctors in Malaysia--a
      nationwide questionnaire survey.
AB  - A self-answered, anonymously completed questionnaire survey was performed between
      June 2002 and May 2003 where doctors from government and private sectors in
      Malaysia were invited to participate by post or during medical meetings. One
      hundred and sixteen government doctors and 110 private doctors provided
      satisfactorily completed questionnaires (effective respondent rate: 30.1%). The
      most preferred medications for 'first-line', 'second-line' and 'third-line'
      treatment were for government doctors: inhaled short-acting beta2-agonist (SABA)
      (98%), inhaled corticosteroids (CS) (75%), and leukotriene antagonist (52%); and
      for private doctors: oral SABA (81%), inhaled CS (68%), and oral CS (58%). The
      first choice inhaler device for most government and private doctors were metered
      dose inhalers, with cost and personal preferences (for private doctors), and
      technical ability (for government doctors) as the key considerations when
      deciding on the choice of device. This benchmark data on the asthma prescribing
      practices of a healthcare delivery system fully dichotomized into government and
      private sector, provides evidence for practice differences affected by the nature
      of the healthcare system, and might have implications on healthcare systems of
      other countries that share similarities with that of Malaysia.

PMID- 15997870
TI  - Asthmatic versus non-asthmatic spontaneous pneumomediastinum in children.
AB  - The aim of this study was to analyze the clinical spectrum and seek potential
      curable causes of spontaneous pneumomediastinum (SPM) in children in order to
      minimize respiratory morbidity. Medical records from 1986 to 2003 were
      retrospectively reviewed at a tertiary pediatric facility in northern Taiwan.
      Sixteen cases of SPM were identified. There were eleven boys and five girls (M:F
      = 2.2:1) and ages ranged from 2 to 17 years (average, 10 years). Cough (81%),
      dyspnea (75%) and chest pain (56%) were the predominant symptoms and expiratory
      wheezing (63%) and neck crepitus (50%) were the most common physical findings.
      The specific sign of Hamman's crunch was noted in only one child initially. A
      coughing-related Valsalva maneuver (13 patients/81%) was the most common cause of
      pneumomediastinum in these children. The most common underlying medical causes
      were asthma (8 patients/50%) and idiopathic origin (5 patients/31%). Acute
      gastroenteritis, foreign body aspiration and mycoplasmal pneumonia were each
      found in one patient respectively. All patients had subcutaneous emphysema on
      initial chest radiographs. Two patients were complicated by pneumothorax and
      required intensive respiratory therapy. The average hospital stay was 4 days
      (range 1-9 days). Rapid resolution of symptoms without long-term sequelae was
      common except for one patient who had hypoxic-ischemic encephalopathy with
      epilepsy after foreign body removal. We conclude that in young teenagers, who
      suffer from cough, dyspnea, chest pain and associated discomfort of throat or
      neck, the diagnosis of SPM should be considered and chest radiography including
      posterior-anterior and lateral projections should be performed to verify the
      diagnosis. Because of the high prevalence of asthma related SPM, children of
      idiopathic SPM should undergo diagnostic pulmonary function tests after the acute
      episode, to establish whether the child has asthma. Targeted investigations of
      the underlying causes of SPM might decrease respiratory morbidity and avoid
      further complications.

PMID- 15997871
TI  - No effect of interleukin-2 on IgE levels given in addition to antiretroviral
      therapy in HIV-infected adults with CD4 >300 cells/mm3.
AB  - HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and
      Th2 cytokines. The objective of the present study was to investigate whether IL-2
      given in addition to antiretrovirals (ARV) would result in lower IgE levels and
      less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and
      were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom
      scoring, PFT and skin prick test (SPT) were performed. It was found that the
      baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively.
      Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1
      antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the
      baseline; however, there were no differences in IgE levels, allergic symptom
      scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It
      was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect
      on atopy.

PMID- 15997872
TI  - Gastroesophageal reflux disease in bronchial asthma and the response to
      omeprazole.
AB  - The objective of this study was to determine the incidence of gastroesophageal
      reflux disease (GERD) in bronchial asthma and the role of omeprazole for
      asthmatics with symptoms of GERD. Seventy asthmatics were screened for GERD by
      questionnaire. Patients with a history suggestive of GERD were confirmed by
      Bernstein test and further investigated for airway responsiveness to instillation
      of HCl in the esophagus. Symptom score, drug score and spirometric values were
      recorded initially and after four weeks of treatment with omeprazole. It was
      found that 74.28% of asthmatics had a history of GERD. Forty patients tested
      positive by Bernstein test and also showed airway responsiveness to instillation
      of HCl in the esophagus. There was a significant improvement in symptom scores (p
      < 0.001), drug scores (p < 0.001) and spirometric values (p < 0.001) after adding
      omeprazole to their treatment regimen. It was concluded that bronchial asthma and
      GERD are associated in the majority of patients (57.14%) and such patients are
      likely to improve with omeprazole.

PMID- 15997873
TI  - Inhibition of tryptase release from human colon mast cells by histamine receptor
      antagonists.
AB  - The main objective of this study was to investigate the ability of histamine
      receptor antagonists to modulate tryptase release from human colon mast cells
      induced by histamine. Enzymatically dispersed cells from human colon were
      challenged with histamine in the absence or presence of the histamine receptor
      antagonists, and the tryptase release was determined. It was found that histamine
      induced tryptase release from colon mast cells was inhibited by up to
      approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine
      and the H2 histamine receptor antagonist cimetidine, respectively, when histamine
      and its antagonists were added to cells at the same time. The H3 histamine
      receptor antagonist clobenpropit had no effect on histamine induced tryptase
      release from colon mast cells at all concentrations tested. Preincubation of
      terfenadine, cimetidine or clobenpropit with cells for 20 minutes before
      challenging with histamine did not enhance the ability of these antihistamines to
      inhibit histamine induced tryptase release. Apart from terfenadine at 100
      microg/ml, the antagonists themselves did not stimulate tryptase release from
      colon mast cells following both 15 minutes and 35 minutes incubation periods. It
      was concluded that H1 and H2 histamine receptor antagonists were able to inhibit
      histamine induced tryptase release from colon mast cells. This not only added
      some new data to our hypothesis of self-amplification mechanisms of mast cell
      degranulation, but also suggested that combining these two types of antihistamine
      drugs could be useful for the treatment of inflammatory bowel disease (IBD).

PMID- 15997874
TI  - Specific immune response and pathological findings in BALB/c mice inoculated with
      recombinant BCG expressing HIV-1 antigen.
AB  - Recombinant BCGs (rBCGs) containing extrachromosomal plasmids with different HIV
      1 insert sequences: nef, env (V3J1 and E9Q), gag p17 or whole gag p55 were
      evaluated for their immunogenicity, safety and persistent infection in BALB/c
      mice. Animal injected with, rBCG-plJKV3J1, rBCG-pSO gag p17 or rBCG-pSO gag p55
      could elicit lymphocyte proliferation as tested by specific HIV-1 peptides or
      protein antigen. Inoculation with various concentration of rBCG-pSO gag p55
      generated satisfactory specific lymphocyte proliferation in dose escalation
      trials. The rBCG-pSO gag p55 recovered from spleen tissues at different time
      interval post-inoculation could express the HIV protein as determined by ELISA
      p24 antigen detection kit. This result indicated that the extrachromosomal
      plasmid was stable and capable to express Gag protein. It was also demonstrated
      that rBCGs did not cause serious pathological change in the inoculated animals.
      The present study suggested the role of BCG as a potential vehicle for using in
      HIV vaccine development.

PMID- 15997875
TI  - De novo mutation causing X-linked hyper-IgM syndrome: a family study in Taiwan.
AB  - X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder
      caused by mutations of the gene encoding the CD40 ligand (CD40L). It is
      characterized by recurrent infections with markedly decreased serum IgG, IgA and
      IgE levels but normal or elevated IgM levels. We report the clinical
      manifestations and complete immune studies in the first family with molecularly
      proven XHIM in Taiwan. A 5-month-old boy presented with rapidly progressive
      pneumonia which responded poorly to antibiotics. High levels of IgM and very low
      levels of IgG, IgA, and IgE were noted in his plasma specimen: IgM, 128 mg/dl;
      IgG, 18 mg/dl; IgA, 4 mg/dl); IgE, 1 IU/ml. Whole blood flow cytometry when he
      was 21 months old showed that only a small percentage (0.48%) of his in vitro
      activated CD4+ T cells expressed CD40L. When he was 3 years old, repeated flow
      cytometry showed essentially the same result (0.4%), compared with his father's
      CD40L expression of over 85%. The patient's mother had moderately decreased CD40L
      expression (74.4%). Hyper-IgM syndrome was confirmed by CD40L mutation analysis
      in the boy, which revealed a Lys 96 stop (nucleotide A307T) in exon 2 of CD40L,
      with a truncated protein resulting in the loss of the entire TNF domain. His
      mother was a carrier and apparently the individual in whom the mutation
      originated. Eleven other family members, including the patient's father, sister,
      and grandmother, and the mother's sisters and their children, all had normal
      results on CD40L mutation analysis. The patient has remained without significant
      bacterial infection on a regimen of monthly IVIG infusion and oral trimethoprim
      sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, although
      he has had recurrent oral ulcers and neutropenia. Bone marrow transplantation is
      planned.

PMID- 15997876
TI  - Focal seizures as an unusual presentation of neonatal lupus erythematosus.
AB  - Neonatal lupus erythematosus is an uncommon passive autoimmune disease in which
      there is a transplacental passage of anti-Ro/SSA and/or anti-La/SSB maternal
      autoantibodies. Common clinical manifestations include cardiac disease, notably
      congenital heart block, cutaneous lupus lesions, hematologic disorders, and
      hepatobiliary disease. During the past decade, however, it has become clear that
      central nervous disease may also be a manifestation of neonatal lupus. We report
      a male neonate with the disease who had focal seizures in addition to cutaneous
      lupus, anemia, and thrombocytopenia. Brain ultrasound revealed normal ventricular
      size without a midline shift or intracranial or intraventricular hemorrhage. A
      brain CT showed generalized low density involving the periventricular and deep
      white matter. A sleep EEG revealed rare spikes axial to the right parietal lobe.
      The neonate had a high titer of antinuclear antibodies (1:640) with a speckled
      pattern, anti-Ro/SSA and anti-La/SSB antibodies, but no anti-dsDNA antibodies. He
      was given anti-convulsant drugs with dramatic improvement of his symptoms. One
      month later, a sleep EEG was normal, and he had no further seizures.

PMID- 15997877
TI  - Epstein-Barr virus serology in the diagnosis of nasopharyngeal carcinoma.
AB  - The antibody levels to viral capsid antigen (VCA) and early antigen (EA) of
      Epstein-Barr virus (EBV) in 164 nasopharyngeal carcinoma (NPC) patients from
      Sarawak, East Malaysia were significantly higher than those in 147 sex, age and
      ethnically matched healthy controls. As diagnostic markers of NPC, IgG/VCA at
      reciprocal titers > or =160 was the most sensitive (89%, with 98% specificity),
      while IgA/EA at > or =5 was the most specific (100%) but the least sensitive
      (75%). The sensitivity and specificity of IgA/VCA at reciprocal titers > or =10
      were 84% and 97%. IgA/VCA has an advantage over IgG/VCA despite the slightly
      lower sensitivity due to its consistently more distinct fluorescence reaction.
      The sensitivity and specificity can be marginally improved by a combination of
      two tests.

PMID- 15997878
TI  - Altered lipid parameters in patients infected with Entamoeba histolytica,
      Entamoeba dispar and Giardia lamblia.
AB  - Information on the effect of parasitic infections on lipid parameters is scarce.
      Certain parasites induce significant changes in lipid parameters, as demonstrated
      by the fact that substitution of lipid/cholesterol for serum in axenic culture
      medium (in vitro) and in experimental models (in vivo) supports vigorous growth
      of Entamoeba histolytica. Thus, significant changes in lipid parameters may be
      induced in an infected host. Blood samples are obtained from intestinal
      amoebiasis patients passing E. histolytica (n=8), E. dispar (n=15) or Giardia
      lamblia (n=9) cysts, or diagnosed with amoebic liver abscess (ALA; n=50) and from
      apparently normal healthy individuals (control group; n=30). Levels of total
      serum cholesterol, high-density lipoprotein and low-density lipoprotein are
      assessed using commercial kits. E. histolytica and E. dispar isolates are
      differentiated by hexokinase isoenzyme electrophoresis and by enzyme-linked
      immunosorbent assay (ELISA; Techlab) tests. Results show that E. histolytica, E.
      dispar and G. lamblia cyst passers had significantly lower levels of total serum
      cholesterol (73.42 +/- 2.24 mg/dL), compared to levels in ALA cases (101 +/- 2.85
      mg/dL) and in controls (166.26 +/- 2.02 mg/dL). Further study of a greater number
      of cases is needed to explore the relevance of this finding.

PMID- 15997879
TI  - Prevalence of Fusobacterium necrophorum and other upper respiratory tract
      pathogens isolated from throat swabs.
AB  - Fusobacterium necrophorum, an anaerobic, Gram-negative rod, has been identified
      recently as a significant cause of persistent sore throat syndrome (PSTS). This
      disease is characterised by chronic, recurrent or persistent sore throat, which
      is believed to respond poorly to penicillin in vivo. The aim of this study is to
      examine the prevalence of F. necrophorum in all throat swabs received in our
      diagnostic microbiology department and to compare the results with those for
      other recognised respiratory pathogens. All throat swabs received in the
      laboratory over a four-week period were cultured for beta-haemolytic
      streptococcus groups A, C and G, Corynebacterium diphtheriae, Arcanobacterium
      haemolyticum and F. necrophorum. Latex agglutination techniques, phenotypic
      reactions and antibiograms are used to identify these organisms. The age of the
      patient and the clinical details as stated on the request form were noted. Among
      a total of 248 samples, 27 were positive for beta-haemolytic streptococcus group
      A, two were positive for beta-haemolytic streptococcus group C, five were
      positive for beta-haemolytic streptococcus group G and 24 were positive for F.
      necrophorum. The most common isolate in the under 20 age group was beta
      haemolytic streptococcus group A. In the over 20 age group, F. necrophorum was
      the pathogen most frequently isolated. A clinical diagnosis of 'sore throat' was
      most likely to be positive for beta-haemolytic streptococcus group A, a clinical
      diagnosis of PSTS was most likely to be positive for F. necrophorum and a
      clinical diagnosis of 'tonsillitis' was equally likely to be caused by beta
      haemolytic streptococcus group A or F. necrophorum. beta-haemolytic streptococcus
      group A was present in 11% of the samples and F. necrophorum was present in 10%
      of the samples. In total, these two pathogens accounted for 18.5% of throat
      infections in the sampled group. The results show that F. necrophorum is as
      significant a cause of throat infection as is beta-haemolytic streptococcus group
      A. Examination of this provisional data suggests that targeting culture towards
      these two pathogens may be possible in certain cohorts of patients if more
      precise clinical data are received from medical staff. However, based on the
      clinical symptoms routinely provided by clinicians requesting microscopy, culture
      and sensitivity on throat swabs, F. necrophorum culture is required on all throat
      swabs received in the laboratory.

PMID- 15997880
TI  - Embryopathy in experimental diabetic gestation: assessment of oxidative stress
      and antioxidant defence.
AB  - Maternal diabetes is associated with an increased rate of congenital fetal
      anomaly. In the present study, diabetes was induced by streptozotocin in female
      rats one week prior to conception and the embryos were examined during
      organogenesis. Experimental diabetes is associated with over-production of free
      radicals and disturbed antioxidant defence, particularly in malformed embryos.
      Oxidative stress is demonstrated by increased MDA accumulation and reduced
      glutathione levels. Despite large differences in the reduced/oxidised glutathione
      ratios during organogenesis in the control, diabetic non-malformed and malformed
      embryo groups, the half-cell redox potential was constant for each group during
      the experimental period. Calculated redox potentials indicated that although
      embryo cells from the control and diabetic mother groups were of the same
      chronological age, the stages of development were different. Increased oxidative
      stress in rat embryos was associated with increased glutathione peroxidases and
      glutathione-S-transferase activity. This may, in part, provide an explanation for
      the observed accumulation of oxidised glutathione in malformed embryos. Moreover,
      decreased levels of vitamin C and selenium were observed. Increased oxidative
      stress and perturbations in antioxidant defence contribute to the high incidence
      of congenital anomalies in experimental diabetic gestation.

PMID- 15997881
TI  - Blood film review by biomedical scientists.
AB  - This study aims to provide evidence of biomedical scientists' competence in blood
      film cytomorphology and to improve continuing assessment and training. Twenty
      photomicrographs are prepared from historical teaching slides, and a slide
      projector timer is designed and built to trigger slide advance automatically
      every 30 sec. Haematology staff in local district general hospitals take part in
      the study. During each visit, the test is explained and participants mark their
      observations on individual results sheets. Two sets (accepted and rejected) of
      observations are generated, which are validated by peer review. The accepted set
      is scored. No evidence is found to prove that members of each department were
      drawn from separate groups (P=0.36). Seniors and routine cytomorphologists are
      compared for each department and a non-zero difference in score was found
      (P=0.00). A comparison is made between the number of times a scored or non-scored
      observation is recorded, resulting in a probability that approaches zero. Thus,
      it is highly unlikely that the observations are drawn from one pool, and the test
      score and ability in cytomorphology would appear to be directly related. This
      study challenges the notion that unrestricted time, clinical data and a
      microscope are required for haematology blood film cytomorphology tests.
      Introduction of this type of test would provide biomedical science with a
      valuable assessment tool.

PMID- 15997882
TI  - Antibody response to Toxoplasma gondii in saliva samples from human
      immunodeficiency virus-infected patients.
AB  - Toxoplasma gondii is an important opportunistic infection among human
      immunodeficiency virus (HIV)-infected patients as it causes fatal encephalitis.
      In the present study, antibody response to T. gondii is assessed in saliva
      samples from 100 HIV-seropositive patients and 25 HIV-negative healthy controls
      by indirect enzyme-linked immunosorbent assay (ELISA). Sensitivity and
      specificity for detection of IgG and IgM in saliva is calculated using a positive
      antibody response in serum samples (from an earlier study) as the gold standard.
      IgG and IgM antibodies were found in 20% and 25% patients, respectively. One
      control subject showed the presence of IgM antibody. Sensitivity for IgG and IgM
      antibodies was 64% and 81.25%, respectively, while specificity was 94.67% and
      85.71%, respectively. This study indicates that saliva samples can be used as an
      alternative to serum samples to detect anti-toxoplasma antibodies, particularly
      IgM, for the diagnosis of toxoplasma encephalitis in HIV/acquired immune
      deficiency syndrome patients.

PMID- 15997883
TI  - Cystic fibrosis genotype and bacterial infection: a possible connection.
AB  - Patients with cystic fibrosis (CF) have repeated bacterial infection of the
      airways, which can lead to chronic infection. There is evidence that disease
      severity is determined by the genetic mutations present. This study aims to
      establish if CF genotype is related to the frequency and types of airway
      bacterial infection. Adult patients attending the regional CF unit are followed
      for two years and assigned to one of three groups depending on whether they are
      chronically infected with Burkholderia cepacia complex (BCC) organisms,
      Pseudomonas aeruginosa, or neither of these organisms. Genotype analysis is
      performed on all patients to determine which of the cystic fibrosis transmembrane
      regulator (CFTR) gene mutations are present. The numbers and types of organism
      with the CFTR mutations isolated from sputum are identified. Data are available
      on 59 patients: 15 colonised with BCC, 24 colonised with P. aeruginosa, and 20
      not colonised with either organism. Twenty patients were homozygous for
      deltaF508, 25 were heterozygous, and the deltaF508 mutation was not present in
      the remaining 14 patients. Patients homozygous or heterozygous for the deltaF508
      mutation had an increased likelihood of colonisation with BCC or P. aeruginosa,
      an increased number of positive sputum cultures and a higher frequency of
      multiple infecting organisms. Cystic fibrosis mutational analysis identified
      seven patients who had the R117H mutation. These patients were less likely to be
      colonised with BCC or P. aeruginosa. In conclusion, patients homozygous or
      heterozygous for the deltaF508 deletion are more likely to suffer airway
      colonisation with BCC or P. aeruginosa, with increased numbers of positive sputum
      cultures and infecting organisms. Those with the R117H mutation are less likely
      to be colonised by Gram-negative organisms.

PMID- 15997884
TI  - Hepatitis C antibodies in asymptomatic first-time blood donors in The Gambia:
      prevalence and risk factors.
AB  - This study evaluates the seroprevalence and risk factors for hepatitis C (HCV)
      antibodies in asymptomatic first-time blood donors in The Gambia. The study
      population includes 460 blood donors (age range: 18-40 years [mean: 27.5]) who
      attended the Royal Victoria Teaching Hospital from July to December 2002.
      Antibodies to hepatitis C are determined using and enzyme-linked immunosorbent
      assay (ELISA) test system. The prevalence of hepatitis C found in this study was
      1.1% (95% CI, 0.16-1.12). Previous history of sexually transmitted disease,
      married men in polygamous relationships, and hospital or clinic-based workers
      were determined to be at risk of acquiring hepatitis C. The study shows that
      seroprevalence of hepatitis C in The Gambia is low compared to other countries in
      the region.

PMID- 15997885
TI  - Antistaphylococcal activity of Omani honey in combination with bovine milk.

PMID- 15997886
TI  - Detection and recovery of Mycobacterium tuberculosis from sputum specimens:
      comparison of the Mycobacteria Growth Indicator Tube and Lowenstein-Jensen
      medium.

PMID- 15997887
TI  - Serial lipoprotein electrophoresis reveals the lipid changes in L-asparaginase
      induced chylomicronaemia syndrome.

PMID- 15997888
TI  - Staphylococci in animals: prevalence, identification and antimicrobial
      susceptibility, with an emphasis on methicillin-resistant Staphylococcus aureus.
AB  - Staphylococci form part of the normal flora of man and a wide variety of animals.
      Some staphylococcal species also cause a wide variety of pyogenic infections. The
      main pathogenic staphylococcus in man is Staphylococcus aureus. Increasingly,
      methicillin-resistant S. aureus (MRSA) has been a problem in the healthcare
      setting. Reports of MRSA in animals have been infrequent; however, evidence
      suggests that MRSA is being isolated increasingly from animals, in particular
      household pets and other companion animals. This article reviews the prevalence
      of pathogenic staphylococci in animals, with an emphasis on the emergence of MRSA
      as a possible animal pathogen.

PMID- 15997889
TI  - Cell-penetrating peptides: [corrected] from inception to application.
AB  - Despite continuing advances in the development of macromolecules, including
      peptides, proteins, and oligonucleotides, for therapeutic purposes, the
      successful application of these hydrophilic molecules has so far been hampered by
      their inability to efficiently traverse the cellular plasma membrane. The
      discovery of a class of peptides (cell-penetrating peptides, CPPs) with the
      ability to mediate the non-invasive and efficient import of a whole host of
      cargoes, both in vitro and in vivo, has provided a new means by which the problem
      associated with cellular delivery can be circumvented. A complete understanding
      of the translocation mechanism(s) of CPPs has so far proven elusive. Initial
      studies indicated an ATP-independent, non-endocytotic mechanism, dependent on
      direct peptide-membrane interactions, making it an enticing challenge from a
      biophysical point of view. However, recent evidence cast doubt on many of the
      earlier results, and led to a re-evaluation of the translocation mechanism of
      CPPs. In this review a brief history of the field will be given, followed by an
      introduction to some of the better known and more widely used CPPs, including
      some of their current applications, and finally a discussion of the translocation
      mechanism(s) and the controversies surrounding it.

PMID- 15997890
TI  - Make ethical recruitment reality.

PMID- 15997891
TI  - Africa: the case for more nurses.

PMID- 15997892
TI  - Flying colours.
AB  - Since 1993, the School of Nursing, Midwifery and Community Health at Glasgow
      Caledonian University has hosted a World Health Organization collaborating centre
      helping nurses and midwives develop good practice in primary care. Now it has
      been elected to host the network secretariat.

PMID- 15997893
TI  - At Grandma's Home. Interview by Charlotte Alderman.
AB  - Among African countries, Uganda has been help up as an example in tackling
      HIV/AIDS. Ruth Sims has pioneered care and treatment for many in need.

PMID- 15997894
TI  - Do doctors really know best?

PMID- 15997895
TI  - Deathly definitions.

PMID- 15997896
TI  - Promoting physical exercise in breast cancer care.
AB  - This article is intended to promote awareness of physical exercise as a safe,
      advantageous and feasible intervention for a patient with breast cancer or
      recovering from it. The numerous and varied benefits of exercise and the
      implications for nursing practice in light of current research evidence are
      discussed.

PMID- 15997897
TI  - Development of core competencies for infection prevention and control.
AB  - The Infection Control Nurses Association (ICNA) has developed a robust framework
      for infection prevention and control practitioners to demonstrate their
      competence. This article describes the process of developing these competencies
      from the first edition (in two parts) to the integrated competencies and
      assessment framework, which may be useful to other specialist groups considering
      the development of competencies relevant to their area of interest. It describes
      how the competencies have been used and how they may be used in the future to
      accredit ICNA members.

PMID- 15997898
TI  - The ward nurse's role in infection control.
AB  - This article surveys the ward nurse's role in reducing the risk of infection.
      Recent developments in infection control are discussed, including nationally
      generated initiatives and how these might be implemented.

PMID- 15997899
TI  - Easing the pain.

PMID- 15997900
TI  - Transatlantic lessons.

PMID- 15997901
TI  - Thirty dimensional.

PMID- 15997902
TI  - A mature approach.

PMID- 15997903
TI  - Should we teach homeopathy to our medical students?

PMID- 15997904
TI  - Suicidal dephosphorylation of thiamine pyrophosphate coupled with pyruvate
      dehydrogenase complex.
AB  - Earlier it was noted that purified pyruvate dehydrogenase complex (PDC) produced
      by "Sigma" usually contains almost saturating amounts of thiamine pyrophosphate
      (ThPP). In this communication we present the observation that the endogenous ThPP
      coupled to PDC is dephosphorylated while staying at -10 degrees C, because in the
      enzyme preparation thiamine monophosphate and un-phosphorylated thiamine appear
      (HPLC determination). Under the same conditions exogenous ThPP is not
      dephosphorylated despite contact with the PDC preparation. This may suggest that
      interactions of some active groups of the enzyme with molecules of endogenous
      ThPP leads to break-up of the phosphoesters bonds, and destruction of the
      coenzyme. Decrease of PDC activity during storage is not in proportion with the
      degree of ThPP dephosphorylation. However the observed instability of PDC
      activity may be a consequence of the spontaneous process of its coenzyme
      autodestruction.

PMID- 15997905
TI  - Acute regulation of the facilitative glucose transporter GLUT1 in a hematopoietic
      cell line.
AB  - This brief review is focused on the short-term regulation of the facilitative
      glucose transporter GLUT1 in megakaryocytic cells M07e. The effects of cytokines
      such as TPO, GM-CSF and SCF and of a low dose of H202 on the transport activity
      and its kinetic parameters are compared. The possible mechanisms and the
      signalling pathways involved in the glucose uptake activation are discussed. A
      role for the cellular redox status in glucose uptake control, possibly related to
      the status of redox-sensitive enzymes such as tyrosine phosphatases, is
      suggested.

PMID- 15997906
TI  - Adenosine: old passion, new perspectives.
AB  - In this review is summarized my research in the adenosine field from the
      beginning of my carrier to day. My research began preparing the degree thesis
      with Prof. Carlo Alfonso Rossi, about the purification and characterization of
      adenosine deaminase. My scientific interest for adenosine has spread during the
      years and I have been interested in the study of ARs and their related
      transduction and in the study of molecular mechanisms involved in homologous and
      heterologous AR receptor regulation.

PMID- 15997907
TI  - Guanidine-induced dissociation of mitochondrial F1-ATPase.
AB  - The effect of guanidine hydrochloride on ATPase activity, gel filtration,
      turbidity, and the fluorescence emission intensity of mitochondrial F1-ATPase was
      examined. Purified F1 from bovine heart mitochondria was slowly inactivated at
      low denaturant concentration, and inactivation was associated with delta and
      epsilon subunit dissociation. delta and epsilon subunits were bound together to
      form a stable and soluble heterodimer. In parallel, appearance of turbidity was
      observed. This was caused by the formation of alpha3beta3gamma non-covalent
      aggregates, as analyzed by SDS-PAGE. Short periods of exposition of the F1
      complex to high concentrations of guanidine hydrochloride (0.8-3 M) again induced
      deltaepsilon dissociation as a heterodimer and the formation of an inactive
      alpha3beta3gamma subcomplex. This eventually dissociated progressively into
      single subunits caused by partial unfolding, as evidenced through changes of the
      protein intrinsic fluorescence emission. Our results suggest that the delta and
      epsilon subunits are loosely bound to alpha3beta3gamma , and play an important
      role in determining structural stability to isolated mitochondrial F1-ATPase.

PMID- 15997908
TI  - Nutritional interventions to counteract oxidative stress in cardiac cells.
AB  - Preventing oxidative damage in the heart is subject of considerable investigation
      and studies developing nutritional intervention methods to attenuate or prevent
      the resulting pathological state of free radical damage are now emerging. In this
      light, a dietary intervention directed to increase the daily intake of
      antioxidant molecules represents a fundamental step to achieve a beneficial
      result. In this minireview the attention is focused on the damage induced in
      cultured cardiac cells by the antitumoral doxorubicin, known for its
      cardiotoxicity, and by hypoxia/reoxygenation that occur in a wide variety of
      important clinical conditions. The identification of antioxidant molecules having
      specific effectiveness in a particular cell type may be useful for the
      development of a prevention strategy specific for free radical induced-diseases
      related to that cell type. Although the connection between consumption of foods
      rich in polyphenolic compounds and the decreased risk of cardiovascular disease
      has been reported, the role of different antioxidant molecules contained in foods
      is still to be elucidated. The protective effect of the polyphenolic components
      of green tea in the prevention/counteraction of cell damage induced in the heart
      by doxorubicin or hypoxia/reoxygenation has been discussed.

PMID- 15997909
TI  - Twenty years of hunting for proteins with Carlo Alfonso Rossi.
AB  - The research accomplished in more thanr twenty years of collaboration with Carlo
      Alfonso Rossi is reviewed. Several lectins and toxic and non-toxic ribosome
      inactivating proteins were identified, purified and characterized. The general
      properties of the proteins are described.

PMID- 15997910
TI  - Evaluation of the lipid composition of human healthy and neoplastic renal
      tissues.
AB  - The assumption that kidney tumors are characterized by high lipid content has
      directed our research towards the evaluation and comparison of lipids in healthy
      and neoplastic human renal tissues. This research appears to have marked
      importance owing to the role of lipids in cancer cell biochemistry. Nuclear
      Magnetic Resonance spectroscopy and chromatographic methods allow the full
      description of the lipidic profile typical of intact medulla, intact cortex,
      clear-cell renal carcinomas, chromophobe-cell renal carcinomas, oncocytomas and
      two samples of medulla infiltrated by a nephrocarcinoma. Significant differences
      among healthy, benign and malignant tissues were shown, and the results were
      discussed in relation to the different roles of each lipidic component and
      compared with the literature data.

PMID- 15997911
TI  - Low molecular weight protein tyrosine phosphatase: catalytic mechanism and
      physiologic function.

PMID- 15997912
TI  - CHART in non-small-cell lung cancer: INCHing forward.

PMID- 15997913
TI  - Defining the need for local therapy in locally advanced prostate cancer: an
      appraisal of the MRC PR07 study.

PMID- 15997914
TI  - The emerging role of high-dose-rate brachytherapy for prostate cancer.
AB  - By placing radioactive sources directly into the cancer, brachytherapy allows
      delivery of a highly conformal radiation dose to the prostate. Permanent seed
      brachytherapy is most commonly used for low-risk cancer, whereas high-dose-rate
      (HDR) brachytherapy is combined with external-beam radiotherapy to treat higher
      risk disease. The high rate of dose delivery and the large fraction size may be a
      radiobiological advantage for tumours with high sensitivity to radiation fraction
      size. The ability to optimise dose delivery allows for exquisite shaping of dose
      around the prostate and sparing of normal tissues. HDR brachytherapy is most
      commonly delivered in two or more fractions of 810 Gy combined with 40-50 Gy
      external beam. Published studies are almost entirely limited to single
      institution case series. Most of the patients treated have relatively
      unfavourable localised disease, with a reported disease-free survival of 68-93%,
      and a local control rate of over 90%. Treatment is well tolerated, with urethral
      stricture the most common late effect (risk around 8%). Early results using HDR
      monotherapy in low-risk disease seem promising. Patients most likely to benefit
      from a combined HDR/external-beam approach have bulky local disease (stage T2b
      T3) or intermediate to high-grade cancers. Prospective multicentre studies of HDR
      brachytherapy have begun in this patient group in Canada and the USA, which
      hopefully will allow future comparisons with high-dose conformal external-beam
      techniques.

PMID- 15997915
TI  - Prostate-specific antigen testing in healthy men: a U.K. perspective.

PMID- 15997916
TI  - Prostate cancer screening in Australasia.

PMID- 15997917
TI  - The pathology of breast cancer and the role of the histopathology laboratory.
AB  - Histopathology plays an important part in determining the treatment strategy for
      women with breast cancer, with the evaluation of breast specimens determining the
      surgical and the oncological therapeutic options used. The correct approach to
      specimens requires integration of clinical and imaging findings. This work is not
      trivial. It is time-consuming and skilled, and requires (and has in place)
      safeguards and checks in the form of national audit and quality-control schemes.
      The pathobiology of breast cancer is diverse, and the current taxonomy, rooted in
      morphological interpretation, has been underscored by molecular observations,
      such as the relationship of E-cadherin mutations to lobular carcinomas.
      Investigation of ductal carcinoma of no special type (NST) reveals covert tumour
      types, such as those with basal or myoepithelial features, whose distinctive
      features are only now being widely recognised. With the rise of modern molecular
      techniques, the demise of diagnostic histopathology has been predicted, but, for
      now and the intermediate future, the histopathologist remains a key element of
      the integrated breast-care team.

PMID- 15997918
TI  - Screening for breast cancer in women at moderate and high risk.

PMID- 15997919
TI  - Chemotherapy for older women with early breast cancer.
AB  - The incidence of breast cancer increases with age, reaching over 300 per 100,000
      in women aged 70-75 years in the U.K., increasing to almost 400 per 100,000 in
      women aged over 85 years. As a healthy 70-year old woman can now expect to live
      for an average of 15 years, control of breast cancer is likely to significantly
      affect survival. Variations exist in surgical care, radiotherapy and
      chemotherapy, depending on age; however, virtually all elderly women with hormone
      responsive disease are given adjuvant endocrine therapy, usually tamoxifen. For
      older women who do not have hormone-responsive cancer, and who have high-risk
      disease characteristics, questions remain over their best management. Overview
      data of adjuvant chemotherapy in clinical trials show a significant benefit of
      chemotherapy for women up to the age of 69 years but, for older women, there are
      too few data to draw any firm conclusions. When considering treatment options for
      older women, assessment is critical; functional status and comorbidity are some
      of the factors linked to shorter survival.

PMID- 15997920
TI  - Platinum-based chemotherapy in metastatic breast cancer: the Leicester (U.K.)
      experience.
AB  - AIMS: After failure of anthracycline- and taxane-based chemotherapy in metastatic
      breast cancer, treatment options until recently were limited. Until the
      introduction of capecitabine and vinorelbine, no standard regimen was available.
      We conducted a retrospective study to determine the efficacy and toxicity of
      platinum-based chemotherapy in metastatic breast cancer. MATERIALS AND METHODS:
      Forty-two women with metastatic breast cancer previously treated with
      anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine
      cisplatin (MVP) (n=23), or cisplatin-etoposide (PE) (n=19), as first-, second-
      and third-line treatment at a tertiary referral centre between 1997 and 2002.
      Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m2) (cycles 1,
      2, 4, 6), vinblastine (6 mg/m2), and cisplatin (50 mg/m2) all on day 1; and
      cisplatin (75 mg/m2) and etoposide (100 mg/m ) on day 1 and (100 mg/m2) orally
      twice a day on days 2-3. RESULTS: The response rate for 40 evaluable patients
      (MVP: n=23; PE: n=17) was 18% (95% confidence interval [CI]: 9-32%). The response
      rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and
      to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%)
      and 47% (26-69%) of women treated with MVP and PE, respectively. After a median
      follow-up of 18 months, 37 women (MVP: n=19; PE: n=18) died from their disease.
      Median (range) progression-free survival and overall survival were 6 months (0.4
      18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival
      for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median
      overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The
      main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in
      women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but
      the incidence of neutropenic sepsis, relative to the number of chemotherapy
      cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2
      admissions per six cycles of chemotherapy. No treatment-related deaths occurred.
      MVP and PE chemotherapy have modest activity and are safe in women with
      metastatic breast cancer.

PMID- 15997921
TI  - The prognostic value of adhesion molecule CD44v6 in women with primary breast
      carcinoma: a clinicopathologic study.
AB  - AIMS: CD44 functions as an adhesion molecule. Within the family of CD44 isoforms,
      the spliced variant 6 has been causally associated with the development of
      metastases and poor prognosis in animal models and several human cancers. The aim
      of this study was to investigate the prognostic value of CD44v6 in women with
      primary breast carcinoma. MATERIALS AND METHODS: The women with primary breast
      carcinoma in this study were followed up clinically for a period of 5 years.
      Clinicopathologic features, including tumour size, axillary nodal status,
      histological grade and pTNM stage, were determined for a cohort of 78 women
      presenting with primary breast carcinoma. Standard immunohistochemistry was used
      to explore CD44v6 expression. The data obtained were analysed by univariate and
      multivariate analyses. RESULTS: Forty-three out of 78 (55%) women with breast
      carcinoma were CD44v6-positive (i.e. over 5% of tumour cells exhibited positive
      staining). Significant sequential increase of CD44v6 expression was observed in
      women with metastases of axillary nodes, tumour size more than 2 cm, advanced
      pTNM stage and survival period less than 5 years. Univariate analysis showed that
      axillary nodal status, primary tumour size, histological grade, and pTNM stage
      were associated with 5-year survival, and CD44v6 expression was associated with
      primary tumour size, axillary nodal status, pTNM stage and 5-year survival. In
      multivariate analysis, using the Cox-regression model, CD44v6 expression was not
      an independent prognostic factor. CONCLUSIONS: CD44v6 expression was correlated
      with tumour size, metastases of axillary nodes, pTNM stage, and 5-year survival;
      however, multivariate analysis revealed that CD44v6 expression failed to be an
      independent predictor of patient prognosis.

PMID- 15997922
TI  - Nuclear localisation of glutathione S-transferase pi is an evaluation factor for
      drug resistance in gynaecological cancers.
AB  - AIMS: Nuclear glutathione S-transferase pi (GST7pi) has been reported to protect
      cancer cells against anticancer drugs. The aim of the present study was to
      evaluate the clinical significance of nuclear GSTpi in gynaecological cancer.
      MATERIALS AND METHODS: We carried out an immunohistochemical analysis of GSTpi,
      and examined the correlation between nuclear GSTpi: expression and prognosis in
      43 epithelial ovarian cancers. We compared expression levels before and after
      chemotherapy in uterine cervical cancers and endometrial cancers. RESULTS: The 5
      year progression-free survival rate of the nuclear GSTpi-positive group was lower
      than that of the cytoplasmic GSTpi-positive group, and was significantly lower
      than that of the negative group (14.3% vs 34.8% vs 66.7%; P = 0.041). The
      expression of nuclear GSTpi was compared before and after chemotherapy in uterine
      cervical and endometrial cancers. In eight out of 12 cases (66.7%), the
      expression turned positive after the chemotherapy. CONCLUSIONS: We suggest that
      nuclear localisation of GSTpi is associated with drug resistance. The nuclear
      localisation of GSTpi in tumour cells is a useful prognosticator, and may
      contribute to the selection of anticancer drugs for gynaecological cancers.

PMID- 15997923
TI  - Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral
      neuropathy: a clinical and electrophysiologic study.
AB  - AIMS: The appearance of peripheral neuropathy is the dose-limiting toxicity in
      many chemotherapy protocols, and glutamine has been proposed as a potentially
      neuroprotective agent in patients receiving paclitaxel. MATERIALS AND METHODS: In
      this non-randomised study, we assessed neurologic signs and symptoms, and changes
      in nerve-conduction studies in 46 consecutive patients given high-dose paclitaxel
      either with (n=17) or without (n=29) glutamine. Neurological assessments and
      electrodiagnostic studies were carried out at baseline and at least 2 weeks
      (median 32 days) after treatment. RESULTS: Patients who received glutamine
      developed significantly less weakness (P = 0.02), less loss of vibratory
      sensation (P = 0.04) and less toe numbness (P = 0.004) than controls. The per
      cent change in the compound motor action potential (CMAP) and sensory nerve
      action potential (SNAP) amplitudes after paclitaxel treatment was lower in the
      glutamine group, but this finding was not statistically significant in these
      small groups. CONCLUSIONS: In this study, serial neurologic assessment of patient
      symptoms and signs seemed to be a better indicator of a possible glutamine effect
      than sensory- or motor-nerve-conduction studies. Prospective randomised trials
      are needed to clarify the effect of glutamine on paclitaxel and other types of
      chemotherapy-induced neuropathy.

PMID- 15997924
TI  - Vascular disrupting agents: a new class of drug in cancer therapy.
AB  - AIMS: To provide a comprehensive overview of the current state of development of
      a novel class of anti-cancer drugs, the vascular disrupting agents (VDAs),
      previously known as vascular targeting agents (VTAs). MATERIALS AND METHODS: A
      comprehensive review, analysis and commentary of the published medical literature
      on VDAs was performed. RESULTS: Tumour vascular targeting therapy exploits known
      differences between normal and tumour blood vessels. VDAs target the preexisting
      vessels of tumours (cf anti-angiogenics), and cause vascular shutdown leading to
      tumour cell death and rapid haemorrhagic necrosis within hours. It is becoming
      clear that VDAs have overlapping activity with anti-angiogenic drugs, which
      prevent the formation of new blood vessels. There are two types of VDA. First,
      biological or ligand-directed VDAs use antibodies, peptides or growth factors to
      target toxins or pro-coagulants to the tumour endothelium. In contrast, small
      molecule VDAs work either as tubulin-binding agents or through induction of local
      cytokine production. VDAs can kill tumour cells resistant to conventional
      chemotherapy and radiotherapy, and work best on cells in the poorly perfused
      hypoxic core of tumours, leaving a viable rim of well-perfused tumour tissue at
      the periphery, which rapidly regrows. Consequently, responses of tumours to VDAs
      given as single agents have been poor; however, combination therapy with
      cytotoxic chemotherapy, external-beam radiotherapy, and radioimmunotherapy, which
      target the peripheral tumour cells, has produced some excellent responses in
      animal tumours. VDAs are generally well tolerated with different side-effect
      profiles to current oncological therapies. Dynamic magnetic resonance imaging is
      most frequently used to obtain a pharmacodynamic end point to determine whether
      the VDA is acting on its intended target. CONCLUSIONS: VDAs are a promising new
      class of drug, which offer the attractive possibility of inducing responses in
      all tumour types with combination therapy.

PMID- 15997925
TI  - Early occurrence of chylothorax related to thoracic irradiation and concomitant
      chemotherapy.

PMID- 15997926
TI  - The importance of recognising nephrotic syndrome as a cause of hypoproteinaemia
      in rectal cancer: Occam's Razor is sometimes violated.

PMID- 15997927
TI  - Herpes simplex encephalitis as a complication of adjuvant chemotherapy treatment
      for breast cancer.

PMID- 15997928
TI  - Unusual metastases from malignant pleural mesothelioma.

PMID- 15997929
TI  - The contribution of cytotoxic chemotherapy to the management of cancer.

PMID- 15997930
TI  - A path yet unpaved.

PMID- 15997931
TI  - Full-mouth rehabilitation of a patient with bulimia nervosa. A case report.
AB  - Anorexia and bulimia nervosa are eating disorders seen mainly in adolescents or
      young patients. The dentist should be in the position to recognize early signs of
      the disorder and alert the patient (and the patient's parents, if necessary) of
      the possible physical, psychologi cal, and dental consequences. Such dental
      treatment may help motivate the patient to confront the problem. In this paper
      the full-mouth rehabilitation, using a combination of galvano- and metal-ceramic
      restorations, of a young patient suffering from bulimia nervosa is described.

PMID- 15997932
TI  - A confocal microscopic evaluation of resin-dentin interface using adhesive
      systems with three different solvents bonded to dry and moist dentinan in vitro
      study.
AB  - OBJECTIVE: Total dehydration of acid-etched dentin is known to cause the collapse
      of collagen fiber, which leads to poor hybridization. Dentin-bonding systems with
      water as a solvent are found to rehydrate the collapsed collagen. Acetone-based
      adhesives are found to compete with moisture, and the acetone carries the resin
      deep into the dentin. The question arises whether to dry the dentin and use a
      water-based adhesive, or to keep the dentin moist and use an acetone- or alcohol
      based adhesive. The aim of this study was to compare different bonding systems
      and techniques to assess which is most successful. A confocal microscope was used
      to evaluate the amount of hybrid layer formation and the depth of resin tag
      formation. METHOD AND MATERIALS: Superficial occlusal dentin specimens from 120
      noncarious, freshly extracted human premolars were used for the study. The dentin
      was etched using 36% phosphoric acid for 15 seconds and then rinsed. The
      specimens were then randomly divided into 4 groups for different drying
      procedures: group I: air-dried for 30 seconds; group II: air-dried for 3 seconds;
      group Ill: blotted dry; group IV: overwet. The specimens were further subdivided
      into 3 groups to be tested with different bonding systems: subgroup A: acetone
      based adhesive (Prime & Bond NT); subgroup B: water-based adhesive (Syntac Single
      Component); subgroup C: water- and ethanol-based adhesive (Single Bond). The
      resulting resin-dentin interfaces were then examined and categorized via confocal
      microscopy, and relative values were assigned to each specimen. RESULTS: Group IV
      (overwet) showed the lowest values, and the highest values were obtained in group
      III. The highest values were seen in group III, subgroup A (blotted dry, acetone
      based bonding agent, Prime & Bond NT). CONCLUSION: Under these conditions, using
      these three bonding systems, maximum hybridization and resin tag formation was
      achieved using acetone-based adhesive on etched dentin kept moist by blot drying.

PMID- 15997933
TI  - Nonalloyed titanium as a bioinert metal--a review.
AB  - Titanium is used for many dental applications and instruments, such as
      orthodontic wires, endodontic files, dental implants, and cast restorations. The
      popularity of titanium is primarily due to its good mechanical properties, its
      high corrosion resistance, and its excellent biocompatibility. A thorough review
      of the medical and dental literature reveals, however, that titanium can also
      cause chemical-biological interactions. Tissue discoloration and allergic
      reactions in patients who have come in contact with titanium have been reported.
      The biostability of titanium is becoming increasingly questioned. At the same
      time, new technologies and materials, such as high-performance ceramics, are
      emerging which could replace titanium in dentistry in the not-too-distant future.

PMID- 15997934
TI  - Intracoronal sealing comparison of mineral trioxide aggregate and glass ionomer.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of
      mineral trioxide aggregate and glass ionomer when placed coronally as double
      sealing materials over gutta percha. METHOD AND MATERIALS: Seventy extracted
      anterior teeth were cleaned, shaped, and obturated with gutta percha and
      Sealapex. After removing 4 mm of coronal gutta percha, the teeth were randomly
      divided into 3 groups. In two experimental groups of 30 teeth each, 4 mm of
      either mineral trioxide aggregate or glass ionomer was placed in the chamber over
      gutta percha. A positive control group of 5 teeth received no barrier. A negative
      control group of 5 teeth was covered completely with sticky wax. All teeth,
      except the negative controls, were covered with 2 layers of sticky wax except for
      the access openings. Teeth were immersed in Pelikan ink for 48 hours, and then
      were decalcified, dehydrated, and cleared. Leakage into the canals was measured
      in millimeters and statistically analyzed between the two experimental groups
      using the Mann-Whitney test. RESULTS: Results showed that the glass ionomer group
      leaked significantly more than the mineral trioxide aggregate group (P < .001).
      CONCLUSION: It was concluded from this study that mineral trioxide aggregate may
      be preferred over glass ionomer as a seal intracoronally following root canal
      treatment to prevent coronal microleakage.

PMID- 15997935
TI  - Ciguatera neurotoxin poisoning mimicking burning mouth syndrome.
AB  - Burning mouth syndrome is a condition in which the patient perceives a sensation
      of intraoral burning, typically of the anterior tongue. This article presents a
      case report of a patient presenting for orofacial pain evaluation in whom
      ciguatera neurotoxin poisoning is diagnosed. The clinician should be aware of
      neurotoxin poisoning as a possible cause of symptoms of burning mouth, especially
      among patients who have recently traveled to a tropical area. Recognition of this
      condition in this case highlights the need for a detailed and accurate patient
      history.

PMID- 15997936
TI  - Efficacy of EDTA-T gel for smear layer removal at root surfaces.
AB  - OBJECTIVE: The purpose of this in vitro study was to investigate the efficacy of
      EDTA gel preparation, associated with texapon detergent (EDTA-T), for removing
      the smear layer at human root surfaces. METHOD AND MATERIALS: An experimental
      smear layer was produced by scaling using periodontal curettes, and the root
      surfaces were etched with the following concentrations of EDTA-T: 5%, 10%, 15%,
      20%, 24%, and negative control (saline solution) for 1, 2, or 3 minutes using
      both passive and active methods. The surfaces were evaluated by scanning electron
      microscopy, and photomicrographs were evaluated in relation to smear removal.
      RESULTS: All EDTA-T groups were more effective than the control group (P <
      .0001). EDTA-T at 15% was more effective when applied by the passive method,
      although this difference was not observed for the active method. The active
      method was statistically better than the passive method (P < .0001). CONCLUSION:
      The etching of the root surface with EDTA-T gel by active application,
      independently of the other factors evaluated, was effective for smear layer
      removal.

PMID- 15997937
TI  - The wand in pulp therapy: an alternative to inferior alveolar nerve block.
AB  - OBJECTIVES: The purpose of the study was to compare children's reactions to
      inferior alveolar nerve injection with traditional syringe and periodontal
      ligament injection with a computerized device (Wand); and to assess the efficacy
      of the anesthesia and their reaction after treatment. METHOD AND MATERIALS:
      Twenty-five children, aged 6 to 10 years, participated in the study. The
      contralateral primary mandibular second molars were treated in 2 separate visits
      with random use of either the Wand or traditional syringe injection. The pain
      perception levels for each step were assessed with Eland Color Scale during the
      preparation. A Mann-Whitney U test was performed to compare the results. The
      patients were asked their preference of technique after the treatment. RESULTS:
      When pain was measured immediately after injection, the traditional syringe was
      found to be more painful than injections with the Wand (P < .05). Pain scores
      with the Wand injections were found to be significantly (P < .05) higher than
      those with traditional inferior alveolar nerve injections at the end of the
      restoration. The overwhelming majority of patients favored the periodontal
      ligament injection with the Wand. CONCLUSION: The Wand technique provided
      significantly lower pain scores during the periodontal ligament injection.
      However, the pain scores during the treatment were significantly higher compared
      with the inferior alveolar nerve injections. Most of the patients stated that
      they preferred the periodontal ligament injection with the Wand to the
      traditional inferior alveolar nerve injection.

PMID- 15997938
TI  - Implant-supported bar-latch overdenture for the severely atrophied, edentulous
      jaw: a case report.
AB  - The removable implant-supported prosthesis is the treatment of choice in some
      clinical situations. Despite its technically demanding fabrication and the
      resultant high cost, the bar-latch overdenture provides stability and is easy for
      patients to manage. A case report illustrating the surgical and prosthetic
      procedures of this treatment option, including laboratory fabrication, is
      presented.

PMID- 15997939
TI  - Odontogenic keratocyst of the right mandibular ascending ramus.

PMID- 15997940
TI  - 'Superbug' threatens intensive care provision.

PMID- 15997942
TI  - The good old days?

PMID- 15997943
TI  - Teaching boys about cancer. Interview by David Crouch.

PMID- 15997944
TI  - The importance of brand continuity in epilepsy drugs.
AB  - Drugs are the mainstay of treatment for epilepsy, and are effective for most
      patients. However, minute differences between generic and branded drugs, and
      between different brands of the same drug, can affect epilepsy control. It is
      vital therefore that patients receive the same brand consistently to avoid loss
      of control.

PMID- 15997945
TI  - What you need to know about rosacea.

PMID- 15997946
TI  - Diclofenac.

PMID- 15997947
TI  - Defining the characteristics of the nurse practitioner role.
AB  - The role of the nurse practitioner (NP) has recently expanded and is now
      recognised in a range of health care delivery settings including primary care. In
      addition, the last few years have seen a proliferation of use of the NP title.
      This article outlines a set of competencies that aim to bring clarity to the
      role.

PMID- 15997948
TI  - Reducing the risk of injuries to staff from insulin pens.
AB  - This article describes problems in the use and disposal of sharps used in the
      administration of insulin therapy in a hospital setting. Subsequent investigation
      and action taken to reduce the risk of needlestick injuries in staff who
      administer insulin therapy with an insulin pen delivery system are also
      discussed.

PMID- 15997949
TI  - Using a coma scale to assess patient consciousness levels.
AB  - The Glasgow coma scale is the most widely used method for assessing a patient's
      level of consciousness. This article outlines the Leeds Teaching Hospitals NHS
      Trust's guidelines to assist practitioners with the practical aspects of carrying
      out and interpreting the scale.

PMID- 15997950
TI  - It's time to ban smoking in public.

PMID- 15997951
TI  - Chronic disease management for patients with respiratory disease.
AB  - National and international awareness of the heavy burden of chronic disease has
      led to the development of new strategies for managing care. Elisabeth Bryant
      explains how self-care, education and support for more patients with complex
      needs should be built into planned care delivery, and emphasises that the patient
      is the key member of the care team.

PMID- 15997952
TI  - Second-hand smoke: how damaging is it to health?
AB  - In the 20th century, over half the English population smoked, but this figure has
      now dropped to a quarter (Office for National Statistics, 2003). A combination of
      scientific evidence, health education campaigns and larger warnings on cigarette
      packets has contributed to achieving this change. Public opinion has also shifted
      dramatically, and most people now accept that being a smoker is damaging to
      health. In 1992, the World Health Organization International Agency for Research
      and Cancer classified second-hand smoke as being 'carcinogenic' to humans (WHO
      International Agency for Research on Cancer, 2002). Following this report, New
      York became one of the first cities in the world to introduce a comprehensive ban
      on smoking in public places to protect employees. In the UK, however, many
      employees, including nurses, are still routinely exposed to tobacco smoke in the
      workplace.

PMID- 15997953
TI  - Criteria for using a nurse-led ventilator-weaning protocol.
AB  - Mechanical ventilation is a process by which gases are moved into and out of the
      lungs by means of a ventilator, a machine that delivers a controlled flow of gas
      to a patient's airway. The reasons for mechanical ventilation include respiratory
      arrest, acute lung injury, critical illness and respiratory support following
      surgery.

PMID- 15997954
TI  - Interstitial lung diseases: clinical features and management.
AB  - Interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases are terms
      used to describe around 200 acute and chronic lung disorders (Raghu and Brown,
      2004). They are a heterogeneous group of disorders of the lower respiratory tract
      that are characterised by both acute and chronic inflammation and a generally
      irreversible and relentless process of fibrosis in the interstitium and the
      alveolar walls (air sacs in the lungs) (Riches et al, 2003).

PMID- 15997955
TI  - Liaising for learning disabilities. Interview by Janis Smy.

PMID- 15997956
TI  - Is nursing losing out to lap dancing?

PMID- 15997957
TI  - What will they think of next?

PMID- 15997959
TI  - New Jersey dentists: hunting down and preventing oral cancer.

PMID- 15997960
TI  - Case report: lesion of endodontic origin or odontogenic neoplasm?

PMID- 15997961
TI  - Dentists' self assessment of burnout: an internet feedback tool.
AB  - OBJECTIVES: The Stress Thermometer is an easily accessible Internet-based
      instrument for feedback on work stress and burnout. The aim of this paper is to
      describe the development of this instrument and to determine its applicability
      within the dental practice. METHODS: The Stress Thermometer was made accessible
      to all members of the Dutch Dental Association, of which 77% of all Dutch
      dentists are members. Frequency of use was determined, and descriptive data was
      collected. RESULTS: During an evaluation period of 5 months at least 12% of all
      possible respondents made use of the Stress Thermometer. Descriptive
      characteristics of the response group, as well as levels of burnout and work
      stress, corresponded with those found in the Dutch dentist population. However,
      some deviations were also present. CONCLUSIONS: Results indicate the
      applicability of the Stress Thermometer to a representative variety of dentists.
      Although the deviations found should not be ignored in future use, the Stress
      Thermometer was successful in reaching a population that is difficult to reach.
      It effectively calls attention to sensitive personal issues concerning work
      related stress and burnout.

PMID- 15997962
TI  - Effects of sanguinaria in fluoride-containing dentifrices on the remineralisation
      of subsurface carious lesion in vitro.
AB  - OBJECTIVE: The purpose of this study was to investigate the potential cariostatic
      benefits of dentifrice containing both fluoride (F) and sanguinaria (SG) in a
      silica abrasive formula using the microbial de- and re-mineralisation cycle
      model. METHODS: Samples of bovine tooth enamel were embedded in resin, polished,
      exposed to a lactate carbopol buffer system for 44 hours, and divided into one
      control and five test groups of 12 specimens each by randomised blocks with VHN
      stratification. Surface microhardness was compared before and after the microbial
      cyclic sequences. RESULTS: VHNs for groups treated with dentifrices containing
      1,000 ppm F from MFP with or without bamboo salt (BS) were significantly higher
      than the control. The groups treated with dentifrices containing F from
      NaF/silica with or without SG had significantly higher VHNs than that with F from
      MFP/DCPD. The VHNs treated with dentifrice containing both NaF-SG demonstrated
      the highest among test groups, indicating that there may be a synergistic effect
      in remineralising the incipient subsurface lesion. CONCLUSION: The dentifrice
      containing both NaF and SG showed a significantly greater effect (p < 0.05) on
      the remineralisation of the enamel lesion than the other test dentifrices.

PMID- 15997963
TI  - Sealing effectiveness of materials used in furcation perforation in vitro.
AB  - OBJECTIVES: In this study the sealing ability of various materials used to repair
      furcation perforations was evaluated. DESIGN: Ninety human molars were
      endodontically treated and a perforation was made in the pulp chamber floor using
      a round bur. The teeth were inserted into a moistened flower sponge and
      perforation sites were sealed with one of the following materials: Mineral
      Trioxide Aggregate (ProRootM), Super-EBA, Vitremer, Hemarcol together with Super
      EBA, Hemarcol together with Vitremer, Tricalcium phosphate together with AH26,
      Cavit W and amalgam. After eight months, the sealing effectiveness of the
      materials was evaluated in a double-blinded trial under a video-microscope by
      detecting the penetration of silver nitrate solution (50%w/w) in longitudinal
      tooth sections. RESULTS: Perforation sites filled with Hemarcol together with
      Vitremer or with MTA exhibited statistically less silver stain penetration while
      Cavit W or Tricalcium phosphate together with AH26 sealer failed to effectively
      seal the perforation sites. CONCLUSIONS: MTA alone or Vitremer in combination
      with a collagen sponge can be used effectively in the treatment of perforations
      in a furcation area.

PMID- 15997964
TI  - Childhood dental history and adult dental attitudes and beliefs.
AB  - OBJECTIVE: To examine associations between childhood dental visits and attitudes
      and beliefs about dental care, and oral health as measured during adulthood.
      METHODS: The data were taken from the Florida Dental Care Study (FDCS), a
      prospective longitudinal study of oral health and dental care, among 683 adults
      45 years of age and older who answered questions about early dental history at
      the 54-month follow-up interview. RESULTS: Fifty-nine per cent (n = 400) reported
      having had a dental visit before 18 years of age. Of those with a childhood
      visit, 72% reported that the first dental visit was a negative experience. Having
      a childhood dental visit was associated with several positive attitudes and
      beliefs about dental care. In addition, having early experiences with a dentist
      was associated with preventive and restorative dental visits and several
      objective and subjective measures of oral health. Having a negative childhood
      experience was associated with only one of the adult dental attitude and beliefs
      subscales, and none of the oral health behaviours. CONCLUSIONS: Our data suggest
      that the socialisation associated with early dental visits may occur even though
      the experience may have been painful or frightening. Although this study design
      precluded direct inference about causation, these findings do support the utility
      of further investigations into possible causative linkages between childhood
      dental experiences and adult attitudinal and dental health outcomes.

PMID- 15997965
TI  - A comparison of the plaque removal efficacy of two power toothbrushes: Oral-b
      Professional Care Series versus Sonicare Elite.
AB  - AIM: To compare the safety and plaque removal efficacy of an oscillating/
      pulsating toothbrush (Professional Care Series, Oral-B Laboratories; PCS) and a
      high frequency toothbrush (Sonicare Elite, Philips Oral Healthcare; SE). METHODS:
      The study had a randomised, examiner-blind, crossover design. Sixty-one subjects
      aged 19-64 years were enrolled. After 23-25 hours of no oral hygiene, subjects
      received an oral tissue examination and those with pre-brushing whole mouth mean
      plaque scores > or = 0.60 measured by the Rustogi modified Navy Plaque Index were
      randomly assigned to treatment sequence. Subjects brushed with their assigned
      toothbrush for 2 minutes using a commercially available dentifrice. Oral tissues
      were then re-examined and post-brushing plaque scores recorded. After a brief
      washout period, the above procedures were repeated with the alternate toothbrush.
      One examiner blinded to the treatment sequence performed all clinical
      measurements. RESULTS: All 61 subjects completed the study. Both toothbrushes
      significantly reduced plaque levels after a single brushing (t-test, p < 0.0001).
      However, the PCS was significantly more effective than the SE in whole mouth
      plaque removal and in reducing plaque from marginal, buccal, lingual and
      approximal surfaces (ANOVA, p < 0.0001). Whole mouth plaque was reduced by 88%
      versus 61% and approximal plaque by 97% versus 73% for the PCS and SE
      toothbrushes, respectively. There was no evidence of hard or soft tissue trauma
      after a single-use of either toothbrush. CONCLUSION: Based on the findings of
      this single-use clinical evaluation, the action of the oscillating/ pulsating
      power toothbrush is more effective at plaque removal than a high frequency power
      toothbrush.

PMID- 15997966
TI  - More attention to public health in the European Union - implications for
      dentistry?
AB  - At present the European Union is developing its competence on health and new
      important issues will be taken on board in European health policy. Increasing
      mobility of people and integration of the applicant countries puts pressure on
      the current health care provision systems. A mandate for an open co-ordination
      process in public health is expected to be given by the European Council. The
      process will start by exchange of information and best practice models. The next
      step will be the presentation of common targets between member countries,
      followed by national action programmes and indicators. It is likely that a lot of
      emphasis will be put on access to health services, comparisons of costs of health
      care and benchmarking the costs of items of care. In the long run this will mean
      convergence of the health care systems. If oral health is to be considered an
      integral part of general health dental professionals need to be aware of and be
      able to influence the actions to be taken.

PMID- 15997967
TI  - 21st century endodontics. Part 2.
AB  - The first paper in this series considered the subject of diagnosis and treatment
      planning for patients with endodontic problems. One of the factors to be taken
      into consideration when deciding whether or not to prescribe root canal treatment
      is the morphology of the root canal system of the root in question. Some
      information may be gleaned from the pre-operative radiograph, but much will be
      part of the practitioner's own knowledge. An understanding of the root canal
      morphology is also essential when cutting efficient and effective access
      cavities, remembering the endodontic cliche that 'access is success'. This paper
      will review canal morphology and access cavities, and then consider how teeth
      under treatment may be isolated from the oral environment to maintain a sterile
      operating environment.

PMID- 15997968
TI  - Dentist-patient relationship and quality care 2. Trust.
AB  - The public in general and individual patients in particular have a high level of
      trust in the dental profession. As trust is an important moral value and a demand
      in health care, a better understanding of the multidimensional nature of trust
      and its impact on the efficiency and quality of care is of utmost importance. The
      core values and principles of dentistry serve to maintain the professional status
      and the associated trust in the profession and thus are of particular concern to
      the individual dentist and to organised dentistry.

PMID- 15997969
TI  - Meeting unmet need: the challenge ahead.

PMID- 15997970
TI  - Bed-rest post-femoral arterial sheath removal--what is safe practice? A clinical
      audit.
AB  - Numbers of patients undergoing coronary angiography and angioplasty procedures
      have increased in England due to targets within the National Service Framework
      for Coronary Heart Disease. Little evidence is available regarding optimal bed
      rest duration for patients post-femoral arterial sheath removal following these
      procedures. Through literature review and clinical benchmarking, we aimed to
      identify what best practice was in the UK and whether bed rest times at our
      centre could be reduced without increasing complications to enable increased day
      case procedures. An audit tool was designed to collect data regarding method of
      obtaining haemostasis, length of bed-rest post-sheath removal and any post
      procedural complications experienced by the patient. From a convenience sample of
      consecutive patients, 195 complete sets of baseline data revealed an average
      (median) period of 6-h bed rest. This was reduced to 3h and audit repeated
      yielding 176 complete data sets using the same audit tool. Femoral wound site
      complication rates were not significantly affected by reducing bed-rest time for
      diagnostic or interventional procedures. These findings contributed to an
      important change in practice, reducing length of stay post-procedure and should
      be re-explored due to increased use of femoral arterial closure devices.

PMID- 15997971
TI  - A review of the information needs of patients with acute coronary syndromes.
AB  - The individual nature of information required by hospitalized patients with
      coronary heart disease (CHD) has been of concern to nurses for over 20 years. An
      information need is not necessarily a gap in knowledge that can be satisfied by
      education. It represents what the patient wants to know from the professional in
      order to cope effectively with the current situation. Through analysis of
      available literature, it seems that patients appear to prioritize information
      that is pertinent to survival, such as symptom management, rather than broader
      lifestyle issues such as exercise and diet. Although information needs are
      individual and subjective to each patient, trends emerge within patient groups.
      Information needs of patients with CHD in coronary care unit and ward setting
      occur across eight or more common areas. Through patient-centred communication,
      patients' f preferences for information in these topics can be derived and used
      as the basis for information delivery. Individual idiosyncratic needs can also be
      noted and addressed.

PMID- 15997972
TI  - Effects of uncertainty on perceived health status in patients with atrial
      fibrillation.
AB  - The nursing discipline has focused on uncertainty as a main theme of research as
      well as an area needing assessment in clinical practice because the concept of
      uncertainty can be applied across diagnostic categories and may be worthwhile in
      explaining responses to illness. This study aimed to examine the effects of
      uncertainty on perceived health status including physical health, mental health,
      and general health within the theoretical framework of uncertainty in illness.
      This descriptive correlational and cross-sectional survey study included 81
      subjects with atrial fibrillation using a face-to-face interview method.
      Individuals with greater symptom severity perceived more uncertainty and
      uncertainty was appraised as a danger rather than opportunity, thus those with
      greater uncertainty appraised a greater danger. While there was no relationship
      between danger appraisal and physical health, the significant relationships were
      shown between danger appraisal and mental health (r = -0.68) and between danger
      appraisal and general health (r = -0.39) respectively. The symptom severity had a
      significant direct effect on general health rather than having indirect effects
      through uncertainty and appraisal. Uncertainty had a significant impact on the
      perception of mental health through danger appraisal, identifying an area for
      nursing interventions. The mediating model of uncertainty with mental health as
      an outcome variable was supported by the empirical data of this study. In order
      to expand the present body of knowledge on uncertainty in illness model,
      recommendations for the future nursing studies and nursing practice were
      included.

PMID- 15997973
TI  - Nurses' knowledge of chest drain care: an exploratory descriptive survey.
AB  - Chest drains are a common feature of patients admitted to acute respiratory or
      cardio-thoracic surgery care areas. Chest drains are either inserted
      intraoperatively or as part of the conservative management of a respiratory
      illness or thoracic injury. Anecdotally, there appears to be a lack of consensus
      among nurses on the major principles of chest drain management. Many decisions
      tend to be based on personal factors rather than sound clinical evidence. This
      inconsistency of treatment regimes, together with the lack of evidence-based
      nursing care, creates a general uncertainty regarding the care of patients with
      chest drains. This study aimed to identify the nurses' levels of knowledge with
      regard to chest drain management. The research objective of this study was to
      describe the nurses' levels of knowledge regarding the care of the patient with
      chest drains. The data were collected using survey method. The results of the
      study revealed deficits in knowledge in a select group of nurses. Several service
      led options exist with regard to improving knowledge in this area, such as
      service study days as well as ward-based tutorials. However, in an era of
      increasing accountability together with the impetus for each nurse to provide
      evidence-based care, it is crucial for individual nurse responsibility in the
      pursuit of knowledge in this area. Nurses must be supported by local practice
      development and through personal portfolio use to identify gaps in knowledge and
      seek appropriate training and resources.

PMID- 15997974
TI  - The handover process and triage of ambulance-borne patients: the experiences of
      emergency nurses.
AB  - One of the most important tasks that a nurse faces in the emergency room, when
      receiving a patient, is handover and the triage function. The aim of the study
      was to explore the experiences of nurses receiving patients who were brought into
      hospital as emergencies by ambulance crews through an analysis of the handover
      and triage process. A qualitative descriptive interview study inspired by the
      phenomenological method was used with six emergency nurses. There are three
      elements to a handover: a verbal report, handing over documented accounts and the
      final symbolic handover when a patient is transferred from the ambulance
      stretcher onto the hospital stretcher. The study identified that the verbal
      communication between ambulance and emergency nurses was often very structured.
      The ideal handovers often involved patients with very distinct medical problems.
      The difficult handover or the 'non-ideal' one was characterized by a
      significantly more complicated care situation. The handover function was pivotal
      in ensuring that the patient received the correct care and that care was provided
      at the appropriate level. The most seriously afflicted patients arrived by
      ambulance; therefore, the interplay between pre-hospital and hospital personnel
      was vital in conveying this important information. To some extent, this
      functioned well, but this research has identified areas where this care can be
      improved.

PMID- 15997976
TI  - [Cardiology and general medicine].

PMID- 15997975
TI  - An evaluation of the critical care assistant role within an acute NHS Trust
      Critical Care Unit.
AB  - This study provides an evaluation of a training programme designed for developing
      six critical care assistants to work alongside registered nurses to care for
      patients within the critical care environment. The programme was run as a pilot
      funded from the Department of Health's 'critical care bid'. At 18 months long,
      the programme incorporated a foundation programme, and National Vocational
      Qualification (NVQ) level 3 in care and adapted Operating Department Practitioner
      (ODP) NVQ units. Six critical care assistants successfully completed the
      programme; however, they all then left the unit to undertake further study for
      pre-registration nursing qualifications. Upon evaluation, a number of key issues
      were identified. Clear definition of the critical care assistants's role is
      essential as are dedicated practice development staff, who focus purely on
      developing the critical care assistant role. More importantly, however, with such
      key changes in the staffing structure within critical care units, appropriate
      change management techniques should be employed, ensuring that all staff
      contributing to the training and development are fully involved from the start.

PMID- 15997977
TI  - [Cardiac murmurs: when to refer for echography?].
AB  - Management of cardiac murmur varies with its characteristics and clinical
      features. Cardiac echography should not be done systematically, as proposed by
      the guidelines. The aim of this article is to define which situations do require
      a cardiac echography, and which do not, thus restricting the expenses without
      harming the patients care.

PMID- 15997978
TI  - [Cardiac MRI in the evaluation of ischemic cardiopathy].
AB  - It is now currently possible with MRI to study global and regional cardiac
      function using dynamic sequences, to follow up myocardial perfusion, or to
      directly visualize myocardial infarctions. This article details the use of these
      new techniques in the diagnosis of ischemic cardiopathy. At least three
      applications are ready to be used in clinical practice: determination of
      viability by MRI, ischemia detection by associating pharmacologic stress and
      finally evaluation of an ischemic cardiopathy as the possible cause of cardiac
      dysfunction. Future developments in the next few years could be the use of MRI
      for differential diagnosis of chest pain in the emergency department as well as
      non invasive coronary angiography.

PMID- 15997979
TI  - [Oral anticoagulants in cardiac patients undergoing elective surgical procedures:
      what attitude to adopt?].
AB  - Clinicians are often required to decide how to manage patients receiving long
      term anticoagulant therapy, and who need a surgical procedure. The decisions are
      based on the perceived risk of continuing or stopping the treatment. Generally,
      warfarin must be stopped before all interventions at high risk of bleeding, but
      can be maintained unchanged before oral and skin surgery. For patients with a
      high risk of thromboembolism, heparin should be administered preoperatively, when
      the INR is <2. The estimation of this risk depends largely on the undelying heart
      disease. In the postoperative phase, the restarting of anticoagulant therapy must
      be weighed against both thromboembolic and hemorragic risks.

PMID- 15997980
TI  - [Dental extractions in patients taking anticoagulants: is alteration of the
      anticoagulant regime necessary?].
AB  - A major concern in the management of patients under anticoagulants is the
      potential for excessive bleeding after dental procedures. Recommendations for the
      administration of oral anticoagulants in conjunction with oral surgery range from
      complete withdrawal of anticoagulants to the maintenance of an unchanged therapy.
      Rising evidences show that the alteration of anticoagulation is not necessary for
      patients with INR of 4 or less previous to tooth extractions. Topical
      antifibrinolytics as tranexamic acid control successfully alveolar bleeding. It
      is time to stop interrupting anticoagulant therapy for oral surgery. A
      theoretical risk of hemorrhage after dental surgery in patients at therapeutic
      levels of anticoagulation exists but it is minimal and is greatly overweighed by
      the risk of thromboembolism after alteration of the anticoagulant therapy.

PMID- 15997981
TI  - [Levosimendan, a revolution in the world of inotropic agents?].
AB  - Levosimendan is the first available drug of a new class of agents called calcium
      sensitizers. It increases cardiac contractility without increasing myocardial
      oxygen consumption. This new molecule has no proarrhythmic effects and has anti
      ischemic properties. Levosimendan is infused over a 24-hour period and its
      hemodynamic effects, similar or superior to those of catecholamines, persist
      during one week. In a selected group of advanced heart failure patients
      levosimendan was associated with a mortality reduction at 14 days and at 6 months
      in comparison with dobutamine. In spite of its cost, this new inotropic agent
      appears very promising and it is expected that it will be widely used.

PMID- 15997982
TI  - [Surgical options for terminal heart failure].
AB  - Terminal heart failure can be the cause or the result of major dysfunctions of
      the organisms. Although, the outcome of the natural history is the same in both
      situations, it is of prime importance to differentiate the two, as only heart
      failure as the primary cause allows for successful mechanical circulatory support
      as bridge to transplantation or towards recovery. Various objective parameters
      allow for the establishment of the diagnosis of terminal heart failure despite
      optimal medical treatment. A cardiac index <2.0 l/min, and a mixed venous oxygen
      saturation <60%, in combination with progressive renal failure, should trigger a
      diagnostic work-up in order to identify cardiac defects that can be corrected or
      to list the patient for transplantation with/without mechanical circulatory
      support.

PMID- 15997983
TI  - [The treatment of venous coronary grafts disease].
AB  - Since the introduction of venous coronary bypass grafting in 1968, venous graft
      disease remains a major therapeutic challenge. The alternative to surgical
      reintervention is saphenous vein graft angioplasty with the combination of distal
      protection and drug eluting stents, available since 2002. Although randomised
      controlled evaluation is still lacking, the early results at 6 months are safe
      and favourable with a stent thrombosis rate below 1,5% and a target lesion
      revascularisation rate near 5%, according to several registries in 2005.

PMID- 15997984
TI  - [The contribution of molecular genetics to clinical cardiology: the example of
      hypertrophic cardiomyopathy].
AB  - Recent advances in molecular genetics have resulted in the identification of
      pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy
      (HCM). In order to integrate this increasing genetic knowledge of HCM into the
      cardiology clinic, we offer all patients and their families diagnosis and genetic
      counselling based on these current data. In addition, within the framework of a
      multidisciplinary project between the Divisions of Medical Genetics, Cardiology
      and Pediatric Cardiology of the University Hospitals of Geneva, we have developed
      a resequencing array enabling rapid molecular diagnosis of HCM. Data from this
      study will enhance our understanding of the aetiology of HCM, and improve our
      knowledge of genotype-phenotype correlations. This information will enable us to
      develop new therapeutic and preventive concepts, with the aim of tailoring
      therapies to the specific genetic variant of each patient and its family.

PMID- 15997985
TI  - [The status of the fetus-- influence of its consideration on medical and
      technical developments].

PMID- 15997986
TI  - [About incentives, competition, and charges].

PMID- 15997987
TI  - ["Mental suffering", small French tragicomedy (Act V)].

PMID- 15997988
TI  - [World-wide eradication of poliomyelitis was not achieved in 2005].

PMID- 15997989
TI  - [Humor].

PMID- 15997990
TI  - What drives pressure ulcer classification--scientific knowledge or fear of
      litigation?

PMID- 15997991
TI  - Pressure ulcers described. 1981.

PMID- 15997992
TI  - Drug-based inhibition of pressure ulcers. 1981.

PMID- 15997993
TI  - The size of the problem of pressure ulcers. 1981.

PMID- 15997994
TI  - The classification and grading of pressure ulcers. 1987.

PMID- 15997995
TI  - Nurses help patients thrive and survive from diagnosis to treatment and beyond.

PMID- 15997996
TI  - How do you prepare patients for the long-term effects of cancer treatment?

PMID- 15997997
TI  - Gifts after death: options for people with cancer.

PMID- 15997998
TI  - Oncology nursing and 2015.

PMID- 15997999
TI  - [Free crystalline silica: a comparison of methods for its determination in total
      dust].
AB  - BACKGROUND: The major objective of the study was to compare and investigate the
      usefulness of quantitative analyses of free crystalline silica (FCS) in the
      assessment of dust exposure in samples of total dust of varied composition, using
      three methods: chemical method in common use in Poland; infrared spectrometry;
      and x-ray powder diffraction. MATERIALS AND METHODS: Mineral composition and FCS
      contents were investigated in 9 laboratory samples of raw materials, materials,
      and industrial wastes, containing from about 2 to over 80% of crystalline silica
      and reduced to particles of size corresponding with that of total dust. Sample
      components were identified using XRD and FT-IR methods. Ten independent
      determinations of FCS with each of the three study methods were performed in dust
      samples. An analysis of linear correlation was applied to investigate
      interrelationship between mean FCS determinations. RESULTS: In analyzed dust
      samples, along with silica dust there were numerous minerals interfering with
      silica during the quantitative analysis. Comparison of mean results of FCS
      determinations showed that the results obtained using the FT-IR method were by 12
      13% lower than those obtained with two other methods. However, the differences
      observed were within the limits of changeability of results associated with their
      precision and dependence on reference materials used. CONCLUSIONS: Assessment of
      occupational exposure to dusts containing crystalline silica can be performed on
      the basis of quantitative analysis of FCS in total dusts using each of the
      compared methods. The FT-IR method is most appropriate for the FCS determination
      in samples of small amount of silica or collected at low dust concentrations; the
      XRD method for the analysis of multicomponent samples; and the chemical method in
      the case of medium and high FCS contents in samples or high concentrations of
      dusts in the work environment.

PMID- 15998000
TI  - [Neurologic and neurophysiologic examinations of workers occupationally exposed
      to aluminium].
AB  - BACKGROUND: Studies conducted to assess aluminum (Al)-induced toxicity to humans
      and environment. It has been implicated that Al is involved in the etiology of
      Alzheimer's disease and other neurodegenerative disorders, though this is
      controversial. The aim of the present study was to assess Al effects on the
      nervous system functions in workers chronically exposed to this metal. METHODS
      AND MATERIALS: The study covered a selected group of 67 male workers (mean age,
      38.7 +/- 10.3 years; range 23-55 years) involved in aluminum production. Their
      employment duration ranged between 2 and 34 years (mean, 14.6 +/- 8.9 years).
      Aluminum oxide (Al2O3) concentrations varied from 0.2 to 1.95 mg/m3 (arithmetic
      mean, 0.40 mg/m3, geometric mean, 0.35 mg/m3, SD = 0.29). Urine aluminum
      concentrations found in smelters ranged from 8.5 to 93.0microg/l (mean, 42.9 +/-
      20.5 microg/l). The control group consisted of 57 men non-occupationally exposed
      to Al matched by gender, age and work shifts. RESULTS: Clinically, headache
      (41,8%), increased emotional irritability (56,7%), concentration difficulty
      (22,4%), insomnia (22,4%) and mood lability (14,9%) predominated among functional
      disorders of the nervous system in workers chronically exposed to Al. The
      objective neurological examinations did not reveal organic lesions in the central
      or peripheral nervous system. In EEG classified as abnormal, generalized and
      paroxysmal changes were most common. Examinations of visual evoked potentials
      (VEP) revealed abnormalities, primarily in the latency of the response evoked.
      CONCLUSIONS: The results of this study suggest that exposure to Al2O3 at
      concentrations within MAC values induces subclinical effect in the nervous
      system.

PMID- 15998001
TI  - [Assessment of the safety of toys with special reference to electromagnetic
      safety in view of binding regulations: a pilot study].
AB  - BACKGROUND: The authors present the result of pilot measurements of
      electromagnetic fields (EMF) in the surrounding of some toys available on the
      Polish market. The measurements were compared with safety standards set in Poland
      to ensure occupational safety and hygiene regarding appliances producing EMF and
      the environmental protection. MATERIALS AND METHODS: EMF intensity was measured
      in the surrounding of six walkie-talkie sets (frequencies: 49.2 MHz; 50 MHz, and
      446 MHz) and 8 radio-controlled (RC) toys (frequencies: 27 MHz; 44.5MHz, and 49
      MHz). Constant EMF was measured in the surrounding of 4 mechanical toys with
      battery powered wire and wireless steering. RESULTS: Walkie-talkie type toys and
      remote controlled toys are the source of EMF with intensity values ranging from 1
      to 21.5 V/m. EMF values over 0.01 mT were not found in the surrounding of
      mechanical toys. CONCLUSIONS: Although EMF values in the surrounding of toys meet
      the requirements defined by CE labeling, several toys produce in its surrounding
      EMF values exceeding maximum allowable intensities according to Polish
      environmental regulations and corresponding with protective zones defined by
      hygiene norms set to protect persons working with EMF-producing devices. The
      magnitude of exposure caused by aforesaid toys depends on both the kind of toys
      and the age of children playing with them.

PMID- 15998002
TI  - [Biomechanical analysis of dynamics and statics of the moving arm in musical
      instrumentalists].
AB  - BACKGROUND: Biomechanical measurements of the motion organ in musicians are a
      separate issue of studies because of specific conditioning of complex motion
      functions which can be observed during playing an instrument. MATERIALS AND
      METHODS: The study was carried out in a group of 368 instrumentalists, taking
      into consideration the measurement of biomechanical parameters before, during and
      after musical performance. RESULTS: An analysis of adduction in the shoulder
      joint during playing an instrument showed that the largest average abduction
      angle appears in cellists, bassists, pianists and flutists, and it is larger in
      the left arm in the case of the double bass, and in the right arm in the case of
      the flute. The lowest average values are lowest in violinists and violists, but
      the static adduction of their right arm is remarkably larger. CONCLUSIONS: The
      study proves that playing an instrument causes specific load of the motion organ,
      both static and dynamic.

PMID- 15998004
TI  - [Readaptation to work after myocardial infarction: model considerations].
AB  - In Poland only 50-60% of persons who have experienced myocardial infarction
      return to work. Bearing in mind that psychophysical condition changes after such
      an event, this group of people has to be readapted to work. Factors that
      determine good work performance among post-infarction workers have been not yet
      investigated. The aim of our study is to identify those factors and to define
      their role in the readaptation process. The first stage of our project involved
      the development of a theoretical model of readaptation to work after myocardial
      infarction. This model is described in this paper. It comprises the following
      components: medical evaluation of the workers' health status, his or her
      subjective assessment of work ability, expectations (optimistic vs. pessimistic
      attitude), motivation to work, social support, and job characteristics.

PMID- 15998003
TI  - [Coexistence of pneumoconiosis with myelodysplastic syndrome in a coal miner
      occupationally exposed to coal dust].
AB  - Pneumoconiosis is the most common occupational disease of the respiratory system.
      The aim of this paper is presentation of case of pneumoconiosis coexisting with
      myelodysplastic syndrome in a former coal miner occupationally exposed to coal
      dust. In a mineral coal miner, aged 56 year, with a 15-year duration of work
      underneath, suffering from pneumoconiosis, pancytopenia was detected. He was
      admitted to the hospital, where myelodysplastic syndrome was diagnosed. The
      patient's condition was gradually worsening, even though chemotherapy was
      applied, he died from thrombocytopenia manifested by bleeding from the digestive
      tract in a relatively short time since diagnosis. The presented case seems to be
      interesting not only in view of possible development of pneumoconiosis as a
      result of occupational exposure to coal dust, typical in this case, but also in
      view of the occurrence of clonal disease of blood several years after cessation
      of exposure.

PMID- 15998005
TI  - [Specific occupational hazards and their health effects among dental
      technicians].
AB  - The authors describe specific hazards occurring at workplaces of dental
      technicians. Exposure to chemical and biological factors in particular and their
      health effects are presented in detail. Among chemical factors, a specific danger
      is associated with allergens (methyl metacrylate, metals, latex, tiurams), which
      may lead to the development of pneumoconiosis. In the authors' opinion, exposures
      to biological hazards need an extensive analysis. A thorough, hygiene and
      epidemiological study of occupational exposure and its health effects among
      dental technicians in Poland would be also very useful.

PMID- 15998006
TI  - [Health risk related to municipal waste incineration].
AB  - There are exposures to various organic and inorganic xenobiotics related to
      municipal waste incineration in work places and environment close to
      incinerators. Among others, these are polychlorinated biphenyls, dioxins, furans,
      chlorophenols, mono- and polycyclic aromatic hydrocarbons, toxic metals and
      irritation gases. Numerous studies revealed that these chemicals and their
      metabolites were generally not elevated in worker's blood and urine and in
      persons living near incinerators. The epidemiological studies indicate increased
      cancer risk and excess of ischemic heart disease in incinerator workers. In
      residents living in the vicinity of incinerators, a slightly increased cancer
      risk, respiratory symptoms, multiple pregnancy, congenital abnormalities, and
      disturbances in thyroid hormone levels were observed. However, these data do not
      provide univocal evidence that the cause-effect relationship between exposure and
      health risk does really exist.

PMID- 15998007
TI  - [Prophylaxis of occupational exposure to tuberculosis among physicians].
AB  - This article presents problems involved in the prevention of tuberculosis, which
      is essential in the practice of occupational medicine physicians. Tuberculosis
      prevention is an important issue since TB morbidity in Poland is relatively high
      compared with other European countries. The authors discuss TB risk factors among
      health care workers, epidemiology of tuberculosis as an occupational disease in
      European countries, including Poland, and the principles of medical prevention.

PMID- 15998008
TI  - [Glutathione functions and factors decreasing its concentration].
AB  - Glutathione (GSH) is the major cellular thiol participating in cellular redox
      reactions. This paper answers two questions: GSH - what is it? What does it do?
      It also describes its forms, the role it plays in cells and organisms, and the
      effect of xenobiotics on GSH concentration.

PMID- 15998009
TI  - A new aluminum hydroxide octamer, [Al8(OH)14(H2O)18](SO4)5 x 16H2O.
AB  - A new aluminum hydroxide cluster with eight Al(III) ions linked together by a
      series of hydroxyl bridges as a sulfate salt has been synthesized from aqueous
      solution and characterized by X-ray crystallography and 27Al NMR spectroscopy.

PMID- 15998010
TI  - Sequestering perrhenate with a borate-based coordination polymer: a model for
      pertechnetate separation.
AB  - Crystals of the layered metal organic framework solid Pb[B(Im)4](NO3)(nH2O) can
      undergo exchange of the nitrate for perrhenate, a model for pertechnetate,
      forming Pb[B(Im)4](ReO4). We can monitor this reaction by 207Pb solid-state NMR
      and can isolate single crystals of the resultant material through growth in the
      presence of an excess of perrhenate. Such a synthetic metal-organic framework
      solid represents a new candidate for pertechnetate-sequestering materials.

PMID- 15998011
TI  - Weak carbon-hydrogen-nitrogen interactions affect the heterocyclic ligand bonding
      modes in barium complexes containing eta2-tetrazolato and eta2-pentazolato
      ligands.
AB  - Treatment of Ba[N(SiMe3)2]2(THF)2 with 2 equiv of dimethylaminotetrazole or
      diisopropylaminotetrazole and 1 equiv of 18-crown-6 afforded Ba[CN4(NMe2)]2(18
      crown-6) (87%) and Ba[CN4(NiPr2)]2(18-crown-6) (79%) as colorless crystalline
      solids. Ba[CN4(NMe2)]2(18-crown-6) contains two 1,2-eta2-tetrazolato ligands and
      one eta6-18-crown-6 ligand. The molecular structure of Ba[CN4(NiPr2)]2(18-crown
      6) is similar to that of Ba[CN4(NMe2)]2(18-crown-6), except that the tetrazolato
      ligands exhibit the isomeric 2,3-eta2-coordination mode and the tetrazolato
      ligand CN4 cores are bent significantly toward the 18-crown-6 ligands. Molecular
      orbital calculations were carried out on the model complexes Ba(azolate)2(18
      crown-6) (azolate = 1,2-eta2-CHN4, 2,3-eta2-CHN4, and eta2-N5) and demonstrate
      that the ligand coordination modes are influenced by intramolecular interactions
      between filled nitrogen orbitals on the azolato ligands and empty C-H sigma*
      orbitals on the 18-crown-6 ligands.

PMID- 15998012
TI  - Structure-function relationships within Keppler-type antitumor ruthenium(III)
      complexes: the case of 2-aminothiazolium[trans-tetrachlorobis(2
      aminothiazole)ruthenate(III)].
AB  - Keppler-type ruthenium(III) complexes exhibit promising antitumor properties. We
      report here a study of 2-aminothiazolium[trans-tetrachlorobis(2
      aminothiazole)ruthenate(III)], both in the solid state and in solution. The
      crystal structure has been solved and found to exhibit classical features.
      Important solvatochromic effects were revealed. Notably, we observed that
      introduction of an amino group in position 2 greatly accelerates chloride
      hydrolysis compared to the thiazole analogue; this latter finding may be of
      interest for a fine-tuning of the reactivity of these novel metallodrugs.

PMID- 15998013
TI  - Phenanthroline-polyoxometalate hybrid compounds and the observation of
      intramolecular charge transfer.
AB  - A phenanthroline ligand has been covalently modified at the 2 and 9 positions by
      an aminophenylhexamolybdate substituent. The 1H NMR spectrum indicated a strong
      electron-withdrawing effect of the hexamolybdate (Mo6O19(2-)) moiety on the
      phenanthroline ligand. UV-vis and cyclic voltammetry showed extended conjugation
      of the hybrid phenanthroline-polyoxometalate compound and the possibility of easy
      oxidation of the extended phenanathroline ligand. Further EPR experiments
      provided strong evidence for an intramolecular charge-transfer process with the
      formation of a phenanthroline cation radical and a reduced hexamolybdate.

PMID- 15998014
TI  - Single-molecule magnets constructed from cyanometalates:
      {[Tp*Fe(III)(CN)3M(II)(DMF)4]2[OTf]2} x 2DMF (M(II) = Co, Ni).
AB  - Treatment of several divalent transition-metal trifluoromethanesulfonates
      [M(II)(OTf)2; M(II) = Mn, Co, Ni] with [NEt4][Tp*Fe(III)(CN)3] [Tp* =
      hydridotris(3,5-dimethylpyrazol-1-yl)borate] in DMF affords three isostructural
      rectangular clusters of {[Tp*Fe(III)(CN)3M(II)(DMF)4]2[OTf]2} x 2DMF (M(II) = Mn,
      3; Co, 4; Ni, 5) stoichiometry. Magnetic studies of 3-5 indicate that the
      Tp*Fe(CN)3(-) centers are highly anisotropic and exhibit antiferromagnetic (3 and
      4) and ferromagnetic (5) exchange to afford S = 4, 2, and 3 spin ground states,
      respectively. ac susceptibility measurements suggest that 4 and 5 exhibit
      incipient single-molecule magnetic behavior below 2 K.

PMID- 15998015
TI  - Ferrocenylalanes: solid-state and solution structures of some new aluminum
      bridged ansa-ferrocenes.
AB  - Addition of dilithiated ferrocene to AlEt2Cl and Al(kappa2-C,NNMe2CH2C6H4)Cl2
      yields the trimeric ferrocenyl derivative 1 and the dimeric [1,1']-ferrocenophane
      2, respectively. Solution spectroscopy is consistent with the solid-state
      structures, which reveal unusual and unprecedented bonding around the aluminum
      centers.

PMID- 15998016
TI  - Controlled decomposition of an indium trihydride adduct: synthesis and
      characterization of the first mixed-oxidation-state indium sub-halide complex
      anion, [In5Br8(quinuclidine)4]-.
AB  - The first example of a compound containing a mixed-oxidation-state indium sub
      halide complex anion, [In5Br8(quinuclidine)4]-, has been accessed by the
      controlled decomposition of an indium trihydride adduct, [InH3(quinuclidine)], in
      the presence of LiBr. An intermediate in this reaction, [InH2Br(quinuclidine)2],
      has been isolated and suggests that its mechanism involves hydride-bromide
      exchange, reductive dehydrogenation, and disproportionation processes.

PMID- 15998017
TI  - Microporous pillared paddle-wheel frameworks based on mixed-ligand coordination
      of zinc ions.
AB  - The reaction of Zn(NO3)2 x 6H2O, various dicarboxylic acids, and either 4,4'
      bipyridine or N,N'-di(4-pyridyl)-1,4,5,8-naphthalenetetracarboxydiimide produces
      a family of anisotropic, mixed-ligand, open-framework compounds featuring paddle
      wheel-type coordination of Zn(II) pairs in two dimensions and pyridyl ligand
      pillaring in the third. Despite 2-fold interpenetration, the compounds contain
      channels of molecular dimensions and several are permanently microporous,
      displaying high internal surface areas.

PMID- 15998018
TI  - Mossbauer, electron paramagnetic resonance, and crystallographic characterization
      of a high-spin Fe(I) diketiminate complex with orbital degeneracy.
AB  - The synthesis and X-ray structure of the low-coordinate, high-spin Fe(I) compound
      LFe(HCCPh) (L = HC(C[tBu]N[2,6-diisopropylphenyl])2]-), 1, are reported. Low
      temperature Mossbauer and electron paramagnetic resonance (EPR) spectroscopies
      reveal that the electronic ground state is a Kramers doublet with uniaxial
      magnetic properties (effective g values g(x) = 8.9, 0 < g(y), g(z) < 0.3) that is
      well isolated from the excited states. The observation of a large and positive
      magnetic hyperfine field, B(int) = +68.8(3) T, demonstrates that the orbital
      angular moment is essentially unquenched along one spatial direction. Relaxation
      rates obtained from variable-temperature Mossbauer spectra were fit to an Orbach
      process, yielding delta = 130-190 cm(-1) for the energy gap ("zero-field
      splitting") between the two Kramers doublets of the S = 3/2 multiplet. Density
      functional theory (DFT) and time-dependent DFT calculations give insight into the
      electronic structures of the ground and excited states. The oxidation state of
      the iron and the bond order of the phenylacetylene ligand in complex 1 are
      analyzed using DFT, showing a substantial back-bonding interaction. Spin-orbit
      coupling acting in the subspace of quasi-degenerate z2 and yz orbitals provides a
      consistent description of both the zero-field splitting and magnetic hyperfine
      parameters that fits the EPR and Mossbauer data for 1. Interestingly, the spin
      orbit coupling involves the same two orbitals (z2, yz) as in the analogous three
      coordinate Fe(II) compounds, because back-bonding significantly lowers the energy
      of the xy orbital, making it the lowest doubly occupied d orbital. Despite the
      different oxidation state and different number of atoms in the first coordination
      sphere, the electronic structure of LFe(I)(HCCPh) can be interpreted similarly to
      that of three-coordinate Fe(II) diketiminate complexes, but with a substantial
      effect of back-bonding. To our knowledge, this is the first detailed Mossbauer
      and EPR study of a structurally characterized high-spin Fe(I) complex.

PMID- 15998019
TI  - XAFS spectral analysis of the cadmium coordination geometry in cadmium thiolate
      clusters in metallothionein.
AB  - We report the combination of measurement and prediction of X-ray absorption fine
      structure (XAFS) data, where the term XAFS refers to the overall spectrum that
      encompasses both the X-ray Absorption Near Edge Structure (XANES) region as well
      as the Extended X-ray Absorption Fine Structure (EXAFS) region, to evaluate the
      cadmium thiolate cluster structures in the metalloprotein metallothionein. XAFS
      spectra were simulated using coordinates from molecular models of the protein
      calculated by molecular mechanics/molecular dynamics (MM3/MD), from NMR analyses,
      and from analysis of X-ray diffraction data. XAFS spectra were also simulated
      using the coordinates from X-ray crystallographic data for [Cd(SPh)4]2-, CdS,
      [Cd2(mu-SPh)2(SPh)4]2-, and [Cd4(mu-SPh)6(SPh)4]2-. The simulated XAFS data that
      were calculated using the FEFF8 program closely resemble the experimental data
      reported for [Cd(SPh)4]2-, CdS, [Cd2(mu-SPh)2(SPh)4]2-, [Cd4(mu-SPh)6(SPh)4]2-,
      rabbit liver metallothionein cadmium alpha-domain (Cd4-alpha MT), and cadmium
      rabbit liver betaalpha metallothionein (Cd7-betaalpha MT). MM3 force field
      parameters were modified to include cadmium-sulfur bonding and were initially set
      to values derived from published X-ray diffraction and EXAFS experimental data.
      The force field was further calibrated and adjusted through comparison between
      experimental spectra taken from the literature and simulated XAFS spectra
      calculated using the FEFF8 program in combination with atomic coordinates from
      MM3/MD energy minimization. MM3/MD techniques were used with the calibrated force
      field to predict the high-resolution structure of the metal clusters in rabbit
      liver Cd7-MT. Structures for Cd3S9 (beta) MT and Cd4S11 (alpha) MT domains from
      MM3/MD calculations and those previously reported for Cd7-MT on the basis of 1H
      and 113Cd NMR data were compared. Structural differences between the different
      models for these cadmium thiolate clusters were evident. Combining the
      measurement and simulation of XAFS data provides an excellent method of
      assessing, modeling, and predicting metal-binding sites in metalloproteins when X
      ray absorption spectroscopy (XAS) data are available.

PMID- 15998020
TI  - Structural characterization of a lanthanum bistriflimide complex,
      La(N(SO2CF3)2)3(H2O)3, and an investigation of La, Sm, and Eu electrochemistry in
      a room-temperature ionic liquid, [Me3N(n)Bu][N(SO2CF3)2].
AB  - The reduction of selected lanthanide cations to the zerovalent state in the room
      temperature ionic liquid [Me3N(n)Bu][TFSI] is reported (where TFSI =
      bistriflimide, [N(SO2CF3)2]-). The lanthanide cations were introduced to the melt
      as the TFSI hydrate complexes [Ln(TFSI)3(H2O)3] (where Ln = La(III), Sm(III) or
      Eu(III)). The lanthanum compound [La(TFSI)3(H2O)3] has been crystallographically
      characterized, revealing the first structurally characterized f-element TFSI
      complex. The lanthanide in all three complexes was shown to be reducible to the
      metallic state in [Me3N(n)Bu][TFSI]. For both the Eu and Sm complexes, reduction
      to the metallic state was achieved via divalent species, and there was an
      additional observation of the electrodeposition of Eu metal.

PMID- 15998021
TI  - Density functional study on dihydrogen activation at the H cluster in Fe-only
      hydrogenases.
AB  - Models simulating the catalytic diiron subcluster [FeFe](H) in Fe-only
      hydrogenases have often been designed for computational exploration of the
      catalytic mechanism of the formation and cleavage of dihydrogen. In this work, we
      extended the above models by explicitly considering the electron reservoir [4Fe
      4S](H) which is linked to the diiron subcluster to form a whole H cluster ([6Fe
      6S] = [4Fe-4S](H) + [FeFe](H)). Large-scale density functional theory (DFT)
      computations on the complete H cluster, together with simplified models in which
      the [4Fe-4S](H) subcluster is not directly involved in the reaction processes,
      have been performed to probe hydrogen activation on the Fe-only hydrogenases. A
      new intermediate state containing an Fe(p)...H...CN two-electron three-center
      bond is identified as a key player in the H2 formation/cleavage processes.

PMID- 15998023
TI  - Geometry of simple molecules. 2. Modeling the geometry of AX3E and AX2E2
      molecules through the nonbonded interaction (NBI) model.
AB  - A new conceptual model of molecular geometry is presented, called the nonbonded
      interaction (NBI) model. This model is applied to the geometries of the AX3E and
      AX2E2 (A = N, O, P, S, As, Se, or Te; X = H, F, Cl, Br, I, CH(3), tBu, CF3, SiH3,
      Sn(tBu)3, or SnPh3) molecule types. For these molecules, the NBI model can be
      quantified on the basis of a balance between terminal atom-terminal atom (X-X)
      interactions and lone pair-terminal atom (E-X) interactions. The empirically
      observed X-A-X angles range from 91.0 degrees (SeH2) to 180 degrees
      (O(Sn(tBu)3)2), and the NBI model predicts the X-A-X angle with a mean unsigned
      error of 1.0 degrees using the empirical A-X distance, 1.5 degrees using the
      LMP2/6-31G** A-X distance, and 1.1 degrees using the MMFF94 A-X distance. This
      level of precision compares well to the LMP2/6-31G**-predicted X-A-X angles and
      is significantly better than the MMFF94-predicted X-A-X angles. Terminal groups
      that are not sufficiently spherical (CF3, SiH3, and SnPh3) can still be addressed
      qualitatively by the NBI model, as can molecules with a mixture of terminal
      groups. The NBI model is able to explain, often quantitatively, the geometry of
      all of the molecules studied, without any additional postulates or extensive
      parametrization.

PMID- 15998022
TI  - Spectroscopic and DFT investigation of [M{HB(3,5-iPr2pz)3}(SC6F5)] (M = Mn, Fe,
      Co, Ni, Cu, and Zn) model complexes: periodic trends in metal-thiolate bonding.
AB  - A series of metal-varied [ML(SC6F5)] model complexes (where L = hydrotris(3,5
      diisopropyl-1-pyrazolyl)borate and M = Mn, Fe, Co, Ni, Cu, and Zn) related to
      blue copper proteins has been studied by a combination of absorption, MCD,
      resonance Raman, and S K-edge X-ray absorption spectroscopies. Density functional
      calculations have been used to characterize these complexes and calculate their
      spectra. The observed variations in geometry, spectra, and bond energies are
      interpreted in terms of changes in the nature of metal-ligand bonding
      interactions. The metal 3d-ligand orbital interaction, which contributes to
      covalent bonding in these complexes, becomes stronger going from Mn(II) to Co(II)
      (the sigma contribution) and to Cu(II) (the pi contribution). This change in the
      covalency results from the increased effective nuclear charge of the metal atom
      in going from Mn(II) to Zn(II) and the change in the 3d orbital populations (d5-
      >d10). Ionic bonding also plays an important role in determining the overall
      strength of the ML(+)-SC6F5(-) interaction. However, there is a compensating
      effect: as the covalent contribution to the metal-ligand bonding increases, the
      ionic contribution decreases. These results provide insight into the Irving
      Williams series, where it is found that the bonding of the ligand being replaced
      by the thiolate makes a major contribution to the observed order of the stability
      constants over the series of metal ions.

PMID- 15998024
TI  - Competitive complexation of gaseous Mn(II) by 1,10-phenanthroline, 2,2'
      bipyridine, and 4,5-diazafluorene.
AB  - Complexes of Mn(II) with 1,10-phenanthroline (phen) and 2,2'-bipyridine (bipy)
      are investigated by means of electrospray ionization (ESI) mass spectrometry.
      Under the conditions used, [MnL(n)]2+ with n = 2 and 3, [MnL(n)Cl]+ with n = 0-2,
      and [Mn2L(n)Cl3]+ with n = 2 and 3 are produced (where L = phen or bipy). The
      collision-induced dissociation (CID) spectra of the mass-selected ions show
      various dissociation pathways, most notable among them is the reduction of the
      ligated Mn(II) to Mn(I) by intracomplex electron transfer. CID experiments of
      mixed-ligand complexes formed upon ESI from solutions which contain both phen and
      bipy exhibit preferential eliminations of bipy, indicating that bipy is a
      significantly weaker ligand for Mn(II) than phen. This effect is mainly
      attributed to the flexibility of the bipy ligand concomitant with thermodynamic
      control in ion dissociation. To support this hypothesis, mixed complexes with
      some methylated derivatives as well as those containing 4,5-diazafluorene (daf)
      are examined also. Interestingly, the differences between the ligands diminish in
      charge-separation reactions of dicationic Mn(II) complexes, due to the joined
      operation of thermodynamic as well as kinetic effects. In addition, the complexes
      [Mn(bipy)]+, [Mn(phen)]+, [Mn(bipy)]2+, [Mn(phen)]2+, and [Mn(bipy)(phen)]2+ are
      computed using the mPW1PW91 hybrid density functional along with the Stuttgart
      Cologne-type pseudopotential and basis-set suite, and relative energies for
      charge-separation reactions and losses of neutral ligands are evaluated.

PMID- 15998025
TI  - Sr2MnSb2: a new ternary transition metal Zintl phase.
AB  - A transition metal-containing Zintl phase, Sr2MnSb2, was prepared from a
      stoichiometric combination reaction of the elements in Sn flux, and its structure
      was determined by single-crystal X-ray diffraction methods. The compound
      crystallizes in the orthorhombic space group Pnma with a = 15.936(3) A, b =
      14.498(3) A, c = 8.2646(17) A, and Z = 12. The structure of Sr2MnSb2 is composed
      of corrugated layers of corner- and edge-shared MnSb4 tetrahedra. The basic
      building unit of the layer is a [Mn3Sb6]12- cluster composed of three edge-shared
      MnSb4 tetrahedra. These trinuclear clusters share four Sb vertexes to form a
      layer with cavities. Sr2+ cations are located at the inter- and intralayer space.
      Magnetic susceptibility measurements indicate an effective magnetic moment of
      4.85 mu(B), a value smaller than what would be expected from Mn2+ ions.

PMID- 15998026
TI  - Directed supramolecular assembly of infinite 1-D M(II)-containing chains (M = Cu,
      Co, Ni) using structurally bifunctional ligands.
AB  - The directed assembly of six different M(II) complexes (M = Cu, Co, and Ni) into
      infinite chains has been achieved by combining anionic chelating ligands (for
      controlling the coordination geometry) with bifunctional ligands containing a
      metal-coordinating pyridyl moiety and a self-complementary hydrogen-bonding
      moiety. Six crystal structures are presented, and in each case, the chelating
      acac ligand occupies the four equatorial coordination sites leaving room for the
      bifunctional ligand to coordinate in the axial positions. The supramolecular
      chemistry, which organizes the coordination complexes into the desired infinite 1
      D chains, is driven by a combination of N-H...N and N-H...O hydrogen bonds.

PMID- 15998027
TI  - Synthetic applications of (Me3SiNSN)2E (E = S, Se) in chalcogen-nitrogen
      chemistry: formation and structural characterization of Cl2TeESN2 (E = S, Se) and
      [PPh4]2[Pd2(mu-Se2N2S)X4] (X = Cl, Br).
AB  - The reaction of (Me3SiNSN)2S with TeCl4 in CH2Cl2 affords Cl2TeS2N2 (1) and that
      of (Me3SiNSN)2Se with TeCl4 produces Cl2TeSeSN2 (2) in good yields. The products
      were characterized by X-ray crystallography, as well as by NMR and vibrational
      spectroscopy and EI mass spectrometry. The Raman spectra were assigned by
      utilizing DFT molecular orbital calculations. The pathway of the formation of
      five-membered Cl2TeESN2 rings by the reactions of (Me3SiNSN)2E with TeCl4 (E = S,
      Se) is discussed. The reaction of (Me3SiNSN)2Se with [PPh4]2[Pd2X6] yields
      [PPh4]2[Pd2(mu-Se2N2S)X4] (X = Cl, 4a; Br, 4b), the first examples of complexes
      of the (Se2N2S)2- ligand. In both cases, this ligand bridges the two palladium
      centers through the selenium atoms.

PMID- 15998029
TI  - Unexpected ferromagnetic interaction in a new tetranuclear copper(II) complex:
      synthesis, crystal structure, magnetic properties, and theoretical studies.
AB  - The new tetranuclear carbonate complex [Cu2L)2(CO3)] x 8H2O (1 x 8H2O) (H3L = (2
      (2-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine)
      has been obtained by two different synthetic routes and fully characterized.
      Recrystallization of 1 x 8H2O in methanol yields single crystals of
      {[(Cu2L)2(CO3)]}2 x 12H2O (1 x 6H2O), suitable for X-ray diffraction studies. The
      crystal structure of 1 x 6H2O shows two crystallographically different
      tetranuclear molecules in the asymmetric unit, 1a and 1b. Both molecules can be
      understood as self-assembled from two dinuclear [Cu2L]+ cations, joined by a mu4
      eta(2):eta(1):eta(1) carbonate ligand. The copper atoms of each
      crystallographically different [(Cu2L)2(CO3)] molecule present miscellaneous
      coordination polyhedra: in both 1a and 1b, two metal centers are in square
      pyramidal environments, one displays a square planar chromophore and the other
      one has a geometry that can be considered as an intermediate between square
      pyramid and trigonal bipyramid. Magnetic studies reveal net intramolecular
      ferromagnetic coupling between the metal atoms. Density functional calculations
      allow the assignment of the different magnetic coupling constants and explain the
      unexpected ferromagnetic behavior, because of the presence of an unusual NCN
      bridging moiety and countercomplementarity of the phenoxo (or carbonate) and NCN
      bridges.

PMID- 15998028
TI  - Corroborative models of the cobalt(II) inhibited Fe/Mn superoxide dismutases.
AB  - Attempting to model superoxide dismutase (SOD) enzymes, we designed two new N3O
      donor ligands to provide the same set of donor atoms observed in the active site
      of these enzymes: K(i)Pr2TCMA (potassium 1,4-diisopropyl-1,4,7-triazacyclononane
      N-acetate) and KBPZG (potassium N,N-bis(3,5-dimethylpyrazolylmethyl) glycinate).
      Five new Co(II) complexes (1-5) were obtained and characterized by X-ray
      crystallography, mass spectrometry, electrochemistry, magnetochemistry, UV-vis,
      and electron paramagnetic resonance (EPR) spectroscopies. The crystal structures
      of 1 and 3-5 revealed five-coordinate complexes, whereas complex 2 is six
      coordinate. The EPR data of complexes 3 and 4 agree with those of the Co(II)
      substituted SOD, which strongly support the proposition that the active site of
      the enzyme structurally resembles these models. The redox behavior of complexes 1
      5 clearly demonstrates the stabilization of the Co(II) state in the ligand field
      provided by these ligands. The irreversibility displayed by all of the complexes
      is probably related to an electron-transfer process followed by a rearrangement
      of the geometry around the metal center for complexes 1 and 3-5 that probably
      changes from a trigonal bipyramidal (high spin, d7) to octahedral (low spin, d6)
      as Co(II) is oxidized to Co(III), which is also expected to be accompanied by a
      spin-state conversion. As the redox potentials to convert the Co(II) to Co(III)
      are high, it can be inferred that the redox potential of the Co(II)-substituted
      SOD may be outside the range required to convert the superoxide radical (O2*-) to
      hydrogen peroxide, and this is sufficient to explain the inactivity of the
      enzyme. Finally, the complexes reported here are the first corroborative
      structural models of the Co(II)-substituted SOD.

PMID- 15998030
TI  - Intermolecular interactions in polymorphs of trinuclear gold(I) complexes:
      insight into the solvoluminescence of Au(I)3(MeN=COMe)3.
AB  - The trinuclear complex, Au(I)3(MeN=COMe)3, which displays a number of remarkable
      properties including solvoluminescence, has been found to crystallize as three
      polymorphs. The new triclinic and monoclinic polymorphs crystallized as colorless
      blocks, whereas the original hexagonal polymorph formed colorless needles. These
      polymorphs differ in the manner in which the nearly planar molecules pack and in
      the nature of the aurophilic interactions between them. Each of the three
      polymorphs of Au(I)3(MeN=COMe)3 shows a distinctive emission spectrum, but only
      the original hexagonal polymorph shows the low-energy emission that is
      responsible for its solvoluminescence. Colorless Au(I)3(n-PentN=COMe)3
      crystallized from diethyl ether as needles of an orthorhombic polymorph and
      blocks of a triclinic polymorph. These polymorphs differ in the orientation of
      the n-Pent substituents, in the orientation of the trimers with respect to one
      another, and in the nature of the aurophilic interactions between the molecules.
      Only the triclinic polymorph of Au(I)3(n-PentN=COMe)3 shows luminescence at room
      temperature, but it is not solvoluminescent. Colorless Au(I)3(i-PrN=COMe)3 has
      also been prepared and crystallographically characterized. The isopropyl groups
      protrude out of the plane of the nine-membered ring and prevent self-association.
      The closest Au...Au contact between molecules is 6.417 A. Crystalline Au(I)3(i
      PrN=COMe)3 is not luminescent at room temperature.

PMID- 15998031
TI  - Oxygen-bridged borate anions from tris(pentafluorophenyl)borane: synthesis, NMR
      characterization, and reactivity.
AB  - The previously known anion [(C6F5)3B(mu-OH)B(C6F5)3]- (2) has been prepared by a
      two-step procedure, involving deprotonation of (C6F5)3BOH2 to give [B(C6F5)3OH]-
      (1), followed by addition of B(C6F5)3. The solution structure and the dynamics of
      2 have been investigated by 1H and 19F NMR spectroscopy. The reaction of [NHEt3]2
      with NEt3 resulted in the formation of [NHEt3]+ [(C6F5)3BOH]-, [NHEt3]+
      [(C6F5)3BH]-, and (C6F5)3B- (CH2CH=N+ Et2). This indicates that in the presence
      of a nucleophile anion 2 can dissociate to B(C6F5)3 and 1. The reaction of
      [HDMAN]2 with 1,8-bis(dimethylamino)naphthalene (DMAN) confirmed this trend. In
      the presence of water, 2 transformed into the adduct
      [(C6F5)3BO(H)H...O(H)B(C6F5)3]- (3), containing the borate 1 hydrogen-bonded to a
      water molecule coordinated to B(C6F5)3. The same compound is formed by treating
      (C6F5)3BOH2 with 0.5 equiv of a base. A competition study established that for 1
      the Lewis acid-base interaction with B(C6F5)3 is about 5 times preferred over H
      bonding to (C6F5)3BOH2. The X-ray single-crystal analysis of [2-methyl-3H
      indolium]3 provided the first experimental observation of an asymmetric H-bond in
      the [H3O2]- moiety, the measured O-H and H...O bond distances being significantly
      different [1.14(2) vs 1.26(2) A]. The reaction of NEt3 with an equimolar mixture
      of B(C6F5)3 and bis(pentafluorophenyl)borinic acid, (C6F5)2BOH, afforded the
      novel borinatoborate salt [NHEt3]+ [(C6F5)3BOB(C6F5)2]- ([NHEt3]4). X-ray
      diffraction showed that the B-O bond distances are significantly shorter than in
      [(C6F5)3B(mu-OH)B(C6F5)3]-. Variable-temperature 19F NMR revealed high mobility
      of the five aryl rings, at variance with the more crowded anion 2. 2D NMR
      correlation experiments showed that in CD2Cl2 the two anions [(C6F5)3BOH]- and
      [(C6F5)3BH]- form tight ion pairs with [NHEt3]+, in which the NH proton
      establishes a conventional (BO...HN) or an unconventional (BH...HN),
      respectively, hydrogen bond with the anion. The diborate anions 2-4, on the
      contrary, gave loose ion pairs with the ammonium cation, due both to the
      delocalized anionic charge and to the more sterically encumbered position of the
      oxygen atoms that should act as H-bond acceptors.

PMID- 15998032
TI  - Synthesis, structure, and magnetic properties of the layered copper(II) oxide
      Na2Cu2TeO6.
AB  - A new quaternary layered transition-metal oxide, Na2Cu2TeO6, has been synthesized
      under air using stoichiometric (with respect to the cationic elements) mixtures
      of Na2CO3, CuO, and TeO2. Na2Cu2TeO6 crystallizes in the monoclinic space group
      C2/m with a = 5.7059(6) A, b = 8.6751(9) A, c = 5.9380(6) A, beta = 113.740(2)
      degrees, V = 269.05(5) A3, and Z = 2, as determined by single-crystal X-ray
      diffraction. The structure is composed of infinity(2)[Cu2TeO6] layers with the Na
      atoms located in the octahedral voids between the layers. Na2Cu2TeO6 is a green
      nonmetallic compound, in agreement with the electronic structure calculation and
      electrical resistance measurement. The magnetic susceptibility shows Curie-Weiss
      behavior between 300 and 600 K with an effective moment of 1.85(2) muB/Cu(II) and
      theta(c) = -87(6) K. A broad maximum at 160 K is interpreted as arising from
      short-range one-dimensional antiferromagnetic correlations. With the aid of the
      technique of magnetic dimers, the short-range order was analyzed in terms of an
      alternating chain model, with the surprising result that the stronger intrachain
      coupling involves a super-superexchange pathway with a Cu-Cu separation of >5 A.
      The J2/J1 ratio within the alternating chain refined to 0.10(1), and the spin gap
      is estimated to be 127 K.

PMID- 15998033
TI  - Synthesis and characterization of diverse coordination polymers. Linear and
      zigzag chains involving their structural transformation via intermolecular
      hydrogen-bonded, interpenetrating ladders polycatenane, and noninterpenetrating
      square grid from long, rigid N,N'-bidentate ligands: 1,4-bis[(x
      pyridyl)ethynyl]benzene (x = 3 and 4).
AB  - The long, rigid ligands 1,4-bis[(3-pyridyl)ethynyl]benzene (L1) and 1,4-bis[(4
      pyridyl)ethynyl]benzene (L2) were used in the synthesis of 10 new organic
      inorganic coordination frameworks, each of them adopting different structural
      motifs. Synthesis, single-crystal X-ray structure determination, and
      spectroscopic and thermogravimetric analyses are presented. The reactions between
      M(NO3)2 x xH2O; M = Cd(II), Cu(II), and Co(II); x = 3-6 and Cu(hfac)2 x H2O [hfac
      = bis(hexafluoroacetylacetonato)] with L1 afforded the following one-dimensional
      zigzag chain structures: [Cd(C20H12N2)0.5(NO3)(CH3OH)]n (1, monoclinic, C2/c; a =
      7.586(1) A, b = 23.222(1) A, c = 13.572(1) A, beta = 92.824(1), Z = 4);
      [{Cu(C20H12N2)(NO3)2(CH3OH)} x CH3OH]n (2, orthorhombic, P2(1)2(1)2(1); a =
      8.589(1) A, b = 15.766(1) A, c = 17.501(1) A, Z = 4); [Co(C20H12N2)2(NO3)2(H2O)2]
      (5, triclinic, P1; a = 7.493(1) A, b = 8.948(1) A, c = 14.854(1) A, alpha =
      100.427(1), beta = 97.324(1), gamma = 110.901(1), Z = 1); [Cu(C20H12N2)(hfac)2]n
      (4, monoclinic, C2/c, a = 18.828(1) A, b = 14.671(1) A, c = 13.427(1) A, beta =
      90.447(1) degrees, Z = 4). Moreover, the minority phase compound formed from
      Cu(NO3)2 x 3H2O and L1 yielded a metallocyclic chain structure,
      [Cu(C20H12N2)(NO3)]n (3, triclinic, P; a = 8.728(1) A, b = 10.018(1) A, c =
      11.893(1) A, alpha = 109.991(1), beta = 97.109(1), gamma = 115.542(1), Z = 1). In
      addition to the dinuclear coordination complex 5, all other polymeric structures
      (1-4) from L1 are composed of interpenetrating 2D and 3D cross-linked zigzag
      chains via hydrogen-bonding interactions. The reactions between M(NO3)2 x xH2O; M
      = Cd(II), Cu(II), and Co(II); x = 3-6 and Cu(hfac)2 x H2O [hfac =
      bis(hexafluoroacetylacetonato)] and L2 were dependent on the nature of the metal
      center and resulted in the formation of four different interpenetrating and
      noninterpenetrating compounds (6-10): [Co(C20H12N2)1.5(NO3)2]n (6, triclinic, P;
      a = 14.172(1) A, b = 15.795(1) A, c = 18.072(1) A, alpha = 115.380(1), beta =
      101.319(1), gamma = 93.427(2), Z = 4), which consists of T-shaped building blocks
      assembled into three-dimensional interpenetrating polycatenated ladders;
      [Cd(C20H12N2)2(NO3)2]n (7, monoclinic, I2/a; a = 11.371(1) A, b = 20.311(2) A, c
      = 15.240(2) A, beta = 100.201(2) degrees, Z = 4), which adopts a two-dimensional
      noninterpenetrating square-grid motif; [Cu(C20H12N2)(hfac)2]n (8, monoclinic,
      I2/a; a = 11.371(1) A, b = 20.311(2) A, c = 15.240(2) A, beta = 100.201(2)
      degrees, Z = 4), composed of three sets of distinct one-dimensional linear
      chains; [Cu(C20H12N2)(EtOH)(NO3)2] [Cu(C20H12N2)1.5(NO3)2] x 2EtOH (9, triclinic,
      P; a = 12.248(2) A, b = 13.711(3) A, c = 18.257(4) A, alpha = 108.078(4) degrees,
      beta = 97.890(4) degrees, gamma = 103.139(5) degrees, Z = 2) and
      [Cu(C20H12N2)(MeOH)(NO3)2] [Cu(C20H12N2)1.5(NO3)2] x 2MeOH (10, triclinic, P; a =
      12.136(1) A, b = 13.738(2) A, c = 17.563(3) A, alpha = 107.663(3) degrees, beta =
      94.805(4) degrees, gamma = 104.021(4) degrees, Z = 2). Both 9 and 10 stack into
      infinite interpenetrating ladders through bundles of infinite chains and are
      described in our preliminary communication.

PMID- 15998034
TI  - Magneto-structural relationships in a series of dinuclear oxalato-bridged
      (diphenyldipyrazolylmethane)copper(II) complexes.
AB  - A series of oxalato-bridged dinuclear copper(II) complexes of the general formula
      [Cu2(Pz2CPh2)2(X)2(mu-C2O4)] (X = Cl- (1), NO3(-) (2), ClO4(-) (3); Pz2CPh2 =
      diphenyldipyrazolylmethane) or [Cu2(Pz(3m)2CPh2)2(H2O)2(mu-C2O4)](NO3)2 x H2O (4)
      (Pz(3m)2CPh2 = diphenylbis(3-methylpyrazolyl)methane) was synthesized where the
      axial ligand was systematically varied to study its effect on structure and
      magnetic coupling. The structures of compounds 1, 2, and 4 have been elucidated
      by single-crystal X-ray diffraction. [Cu2(Pz2CPh2)2(Cl)2(mu-C2O4)] and
      [Cu2(Pz2CPh2)2(NO3)2(mu-C2O4)] are isostructural and crystallize in the triclinic
      system, space group P, Z = 2, with a = 8.6155(8) A, b = 10.1435(9) A, c =
      11.3612(11) A, alpha = 95.535(2) degrees, beta = 110.303(2) degrees, and gamma =
      106.111(2) degrees for 1 and with a = 8.863(7) A, b = 10.241(9) A, c = 11.425(10)
      A, alpha = 98.985(14) degrees, beta = 110.449(13) degrees, and gamma =
      103.664(14) degrees for 2. [Cu2(Pz(3m)2CPh2)2(H2O)2(mu-C2O4)] x NO3 x H2O
      crystallizes in the monoclinic system, space group C2/c, Z = 4, with a =
      23.4588(14) A, b = 8.8568(5) A, c = 21.7818(13) A, alpha = gamma = 90 degrees,
      and beta = 100.8890(10) degrees. Variable-temperature magnetic susceptibility
      studies indicate that all four compounds are strongly antiferromagnetically
      coupled (2J/k = -364, -344 cm(-1) (2), -424 cm(-1) (3), and -378 cm(-1) (4)).
      Magnetic and EPR results are discussed with respect to structural parameters to
      explore possible magneto-structural correlations.

PMID- 15998035
TI  - Energetic azolium azolate salts.
AB  - Energetic salts comprising substituted imidazolium and 1,2,4-triazolium cations
      and 4,5-dinitro-imidazolate and 5-nitrotetrazolate anions were synthesized and
      characterized. On the basis of experimentally obtained heats of combustion, the
      calculated heats of formation range from deltaHf(o) degrees = 80 (3) to 1071
      kJ/mol (13). Imidazolate salts are more dense but have lower heats of formation
      than their tetrazolate analogues. Salts 4, 5, 8, and 11-14 fall into the ionic
      liquid class (mp < 100 degrees C). The structure of 1,2,4-triazolium 5
      nitrotetrazolate (10) was confirmed by X-ray analysis.

PMID- 15998036
TI  - Vanadium(III) and vanadium(V) amine tris(phenolate) complexes.
AB  - The coordination chemistry of amine tris(phenolate) ligands around V(III) and
      V(V) is described for the first time. Three amine tris(phenolate) ligands were
      employed featuring different steric and electronic influence exerted by the
      phenolate substituents in the ortho and para positions being either t-Bu, Me, or
      Cl. V(III) complexes of all ligands (1-3) were readily obtained by reaction
      between the ligand precursors and VCl3(THF)3 in the presence of triethylamine.
      The complexes obtained were pentacoordinate, a THF ligand completing the
      coordination sphere of the metal, which was found to be of almost perfect TBP
      geometry, as revealed by crystallography. V(V) oxo complexes of all the ligands
      (4-6) were readily obtained by a reaction between the ligand precursors and
      VO(OPr)3. The oxo complexes of the alkyl-bearing ligands (4 and 5) could also be
      synthesized by the air oxidation of the corresponding V(III) complexes (1 and 2);
      however, the attempted air oxidation of the V(III) complex bound to the electron
      poor ligand (3) did not yield the corresponding oxo complex 6. 1H NMR and
      crystallographic analysis of complexes 4 and 5 supported their TBP structures.
      Complex 6, on the other hand, was found to be composed of a TBP complex (6a) and
      an octahedral complex (6b) in equilibrium, the octahedral complex being more
      stable at lower temperatures. An X-ray structure of 6b revealed a mononuclear oxo
      complex, the sixth coordination site being occupied by an aqua ligand to which
      two THF molecules are H-bonded. Complexes 4-6 catalyze the epoxidation of olefins
      by t-BuOOH, albeit slowly. These complexes may thus be considered as structural
      and functional models of vanadium-dependent haloperoxidase enzymes.

PMID- 15998037
TI  - Metal-metal interactions in mixed-valence [M2Cl9]2- species: electronic structure
      of d1d2 (V, Nb, Ta) and d4d5 (Fe, Ru, Os) face-shared systems.
AB  - The molecular and electronic structures of mixed-valence d1d2 (V, Nb, Ta) and
      d4d5 (Fe, Ru, Os) face-shared [M2Cl(9)]2- dimers have been calculated by density
      functional methods in order to investigate metal-metal bonding in this series.
      General similarities are observed between d1d2 and d4d5 systems and can be
      considered to reflect the electron-hole equivalence of the individual d1-d5 and
      d2-d4 configurations. The electronic structures of the dimers have been analyzed
      using potential energy curves for the broken-symmetry and other spin states
      resulting from the d1d2 and d4d5 coupling modes. In general, a spin-doublet (S =
      1/2) state, characterized by delocalization of the metal-based electrons in a
      metal-metal bond with a formal order of 1.5, is favored in the systems containing
      4d and 5d metals, namely, the Nb, Ta, Ru, and Os dimers. In contrast, the
      calculated ground structures for [V2Cl9]2- and [Fe2Cl9]2- correspond to a spin
      quartet (S = 3/2) state involving weaker coupling between the metal centers and
      electron localization. In the case of [Ru2Cl9]2-, both the spin-doublet and spin
      quartet states are predicted to be energetically favored suggesting that this
      species may exhibit double-minima behavior. A comparison of computational results
      across the (d1d1, d1d2, d2d2) [Nb2Cl9]z- and [Ta2Cl9]z- and (d4d4, d4d5, d5d5)
      [Ru2Cl9]z- and [Os2Cl9]z- series has revealed that, in all four cases, the
      shortening of the metal-metal distances correlates with an increase in formal
      metal-metal bond order.

PMID- 15998038
TI  - The stability and eventual lone pair distortion of the hexahalide complexes and
      molecules of the fifth to eighth main-group elements with one lone pair, as
      isolated entities or in oligomeric clusters: a vibronic coupling and DFT study.
AB  - The introduced DFT-supported vibronic coupling model together with the hardness
      rule indicates, for the title compounds, that the tendency toward lone pair (LP)
      distortions decreases with increasing coordination number (CN) and upon
      proceeding from fluoride to iodide as the ligands. Thus, only some hexafluoro
      complexes and molecules are calculated to actually undergo LP deformations; here,
      from the possible highest-symmetry deformations, those with C(4v) geometry
      possess the lowest energy, leading to the complete ablation of one ligand and,
      hence, explaining the nonexistence of the complexes AsF6(3-), SbF6(3-), and SF6(2
      ). If a lower-symmetry strain is imposed on the octahedral species, for example,
      induced by the simultaneous presence of terminal and bridging ligands in
      oligomers, the vibronic energy potential is activated. It may induce pronounced
      distortions, which are much larger than those of analogous clusters with central
      ions lacking the LP. Dimers and tetramers with common edges and faces are
      investigated, with the predicted and calculated deformations of the constituting
      octahedra again following the stability sequence C(4v) > C(2v) > C(3v). The model
      nicely accounts for the observed trends, as well as reproduces the experimental
      structures and energy balances, at least semiquantitatively; its predictive power
      exceeds that of the valence-shell electron-pair repulsion concept.

PMID- 15998039
TI  - Acid-base and metal-ion-binding properties of 9-[2-(2
      phosphonoethoxy)ethyl]adenine (PEEA), a relative of the antiviral nucleotide
      analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). An exercise on the
      quantification of isomeric complex equilibria in solution.
AB  - The acidity constants of 3-fold protonated 9-[2-(2-phosphonoethoxy)ethyl]adenine,
      H3(PEEA)+, and of 2-fold protonated (2-phosphonoethoxy)ethane, H2(PEE), and the
      stability constants of the M(H;PEEA)+, M(PEEA), and M(PEE) complexes with M2+ =
      Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ have been
      determined (potentiometric pH titrations; aqueous solution; 25 degrees C; I = 0.1
      M, NaNO3). It is concluded that in the M(H;PEEA)+ species, the proton is at the
      phosphonate group and the metal ion at the adenine residue. The application of
      previously determined straight-line plots of log K(M(R-PO3))M versus pK(H(R
      PO3))H for simple phosph(on)ate ligands, R-PO3(2-), where R represents a residue
      that does not affect metal-ion binding, proves that the M(PEEA) complexes of
      Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ as well as the M(PEE) complexes of Co2+, Cu2+,
      and Zn2+ have larger stabilities than is expected for a sole phosphonate
      coordination of M2+. For the M2+ complexes without an enhanced stability (e.g.,
      Mg2+ or Mn2+), it is concluded that M2+ binds in a monodentate fashion to the
      phosphonate group of the two ligands. Combination of all of the results allows
      the following conclusions: (i) The increased stability of the Co(PEE), Cu(PEE),
      Zn(PEE), and Co(PEEA) complexes is due to the formation of six-membered chelates
      involving the ether-oxygen atom of the aliphatic residue (-CH2-O-CH2CH2-PO3(2-))
      of the ligands with formation degrees of about 15-30%. (ii) Cd(PEEA) forms a
      macrochelate with N7 of the adenine residue (formation degree about 30%);
      Ni(PEEA) has similar properties. (iii) With Zn(PEEA), both mentioned types of
      chelates are observed, that is, Zn(PEEA)(cl/O) and Zn(PEEA)(cl/N7), with
      formation degrees of about 13 and 41%, respectively; the remaining 46% is due to
      the "open" isomer Zn(PEEA)(op) in which the metal ion binds only to the PO3(2-)
      group. (iv) Most remarkable is Cu(PEEA) because a fourth isomer,
      Cu(PEEA)(cl/O/N3), is formed that contains a six-membered ring involving the
      ether oxygen next to the phosphonate group and also a seven-membered ring
      involving N3 of the adenine residue with a very significant formation degree of
      about 50%. Hence, PEEA(2-) is a truly ambivalent ligand, its properties being
      strongly dependent on the kind of metal ion involved. Comparisons with M2+
      complexes formed by the dianions of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA)
      and related ligands reveal that five-membered chelates involving an ether-oxygen
      atom are considerably more stable than the corresponding six-membered ones. This
      observation offers an explanation of why PMEA is a nucleotide analogue with
      excellent antiviral properties and PEEA is not.

PMID- 15998040
TI  - Lanthanide clusters with internal Ln: fragmentation and the formation of dimers
      with bridging Se(2-) and Se2(2-) ligands.
AB  - Reactions of "LnI(x)(SePh)(3-x)" (Ln = Dy, Ho) with elemental S/Se give
      (THF)14Ln10S6(Se2)6I6. The compounds are composed of a Ln6S6 double cubane core,
      with two twisted "Ln2(SeSe)3" units condensed onto opposing rectangular sides of
      the Ln6S6 fragment. This deposition of Ln2Se6 totally encapsulates the two
      central Ln's with chalcogen atoms (four S and four Se atoms), excluding neutral
      THF donors or iodides from the two primary coordination spheres. Reactions of
      Ln(10) clusters with a stronger Lewis base result in fragmentation and, in the
      case of Ln = Er, the isolation of (py)6Er2(Se2)(S0.8Se0.2)I2, with two Ln(III)
      ions spanned by E2- and (EE)2- ligands. The related homochalcogen dimers
      (py)6Ln2(Se2)(Se)Br2 (Ln = Ho, Yb) were prepared to establish that such molecules
      could be prepared rationally, and to confirm the isolability of E2- ligands
      coordinated to only two sterically unconstrained Ln ions.

PMID- 15998041
TI  - Voltammetric studies on the reduction of polyoxometalate anions in ionic liquids.
AB  - The electrochemical reduction of tetrabutylammonium salts of isostructural pairs
      of polyoxometalates [Bu4N]2[M6O19], [Bu4N]4[alpha-SiM12O40], and [Bu4N]4[alpha
      S2M18O62] (M = Mo or W) has been investigated at glassy carbon electrodes in
      dissolved and surface-confined states in ionic liquids and other media. In the
      ionic liquid 1-n-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF(6)],
      between two and six reversible one-electron-transfer processes were detected.
      Detailed studies on the process [alpha-S2W18O62](4-/5-) in a range of ionic
      liquids, water, and conventional organic solvents (containing 0.1 M electrolyte)
      suggest that the polarity of the medium plays a key role in the determination of
      the reversible potential. Reduction processes involving very highly charged
      [alpha-S2W18O62](8-/9-/10-) species are strongly influenced by the purity of the
      medium.

PMID- 15998042
TI  - Carbon-bridged bis(phenolato)lanthanide alkoxides: syntheses, structures, and
      their application in the controlled polymerization of epsilon-caprolactone.
AB  - A convenient method for the synthesis of lanthanide alkoxo complexes supported by
      a carbon-bridged bis(phenolate) ligand 2,2'-methylenebis(6-tert-butyl-4
      methylphenoxo) (MBMP2-) is described. The reaction of (C5H5)3Nd with MBMPH2 in a
      1:1 molar ratio in THF gave the bis(phenolato)lanthanide complex
      (C5H5)Nd(MBMP)(THF)2 (1) in a nearly quantitative yield. Complex 1 further
      reacted with 1 equiv of 2-propanol in THF to yield the bis(phenolato)lanthanide
      isopropoxide [(MBMP)2Nd(mu-OPr(i))(THF)2]2 (2) in high yield. Complex 2 can also
      be synthesized by the direct reaction of (C5H5)3Nd with MBMPH2 in a 1:1 molar
      ratio and then with 1 equiv of 2-propanol in situ in THF. Thus, the analogue
      bis(phenolato)lanthanide alkoxides [(MBMP)2Ln(mu-OR)(THF)2]2 [R = Pr(i), Ln = Yb
      (3); R = Me, Ln = Nd (4), Yb (5); R = CH2Ph, Ln = Nd (6), Yb (7)] were obtained
      by the reactions of (C5H5)3Ln (Ln = Nd, Yb) with MBMPH2 and then with 2-propanol,
      methanol, or benzyl alcohol, respectively. The ytterbium complex
      {[(MBMP)2Yb(THF)2]2(mu-OCH2Ph)(mu-OH)} (8) was also isolated as a byproduct. The
      single-crystal structural analyses of complexes 1-3 and 8 revealed that the
      coordination geometry around lanthanide metal can be best described as a
      distorted tetrahedron in complex 1 and as a distorted octahedron in complexes 2,
      3, and 8. A O-H...Yb agostic interaction was observed in complex 8. Complexes 2-7
      were shown to be efficient catalysts for the controlled polymerization of epsilon
      caprolactone.

PMID- 15998043
TI  - Platinum(II) complex as an artificial peptidase: selective cleavage of peptides
      and a protein by cis-[Pt(en)(H2O)2]2+ ion under ultraviolet and microwave
      irradiation.
AB  - Two synthetic peptides were completely cleaved by the cis-[Pt(en)(H2O)2]2+ (en is
      ethylenediamine) complex at pH 2.5 under thermal heating at 60 degrees C in a
      selective way: only the amide bonds involving the carboxylic group of the
      methionine residue, i.e., the Met-Z bonds (where the residue Z has a
      noncoordinating side chain), were hydrolyzed. Under irradiation at 300 nm, the
      rate constants for these cleavage reactions were approximately doubled, but side
      reactions occurred. Under microwave irradiation, the rate constants were
      increased 2-3 times at 60 degrees C and ca. 7 times at 100 degrees C, and no side
      reactions were detected. Microwave irradiation similarly accelerated the complete
      and selective cleavage of Met-Z bonds in cytochrome c at 60 degrees C in
      comparison with this cleavage under thermal heating, again without detected side
      reactions. The microwave-assisted cleavage of peptides and proteins by the
      platinum(II) reagent holds promise in proteomics and other biotechnological
      applications.

PMID- 15998044
TI  - Zirconium and hafnium complexes containing bidentate diarylamido-phosphine
      ligands.
AB  - The first examples of mononuclear, structurally characterized triarylphosphine
      complexes of zirconium and hafnium are reported. The metathetical reactions of
      MCl4(THF)2 (M = Zr, Hf) with [iPrNP]Li(THF)2 ([iPrNP]- = N-(2
      (diphenylphosphino)phenyl)-2,6-diisopropylanilide) or [MeNP]Li(THF)2 ([MeNP]- = N
      (2-(diphenylphosphino)phenyl)-2,6-dimethylanilide) in toluene at -35 degrees C
      produced the corresponding [iPrNP]MCl3(THF) and [MeNP]2MCl2, respectively, in
      high yield. In contrast, attempts to prepare [MeNP]MCl3(THF) and [iPrNP]2MCl2 led
      to the concomitant formation of mono- and bis-ligated complexes, from which
      purification proved rather ineffective. The solution and solid-state structures
      of [iPrNP]MCl3(THF) and [MeNP]2MCl2 were studied by multinuclear NMR spectroscopy
      and X-ray crystallography. The geometry of these six-coordinate complexes is best
      described as a distorted octahedron in which the chloride ligands in
      [iPrNP]MCl3(THF) adopt a virtually meridional coordination mode whereas those in
      [MeNP]2MCl2 are trans to each other.

PMID- 15998045
TI  - Nitrile-amidine coupling at Pt(IV) and Pt(II) centers. An easy entry to
      imidoylamidine complexes.
AB  - Treatment of trans-[PtCl4(RCN)2] (R = Me, Et, Ph, NEt2) with 2 equiv of the
      amidine PhC(=NH)NHPh in a suspension of MeCN (R = Me), CHCl3 (R = Et, Ph), or in
      CHCl3 solution (R = NEt2) results in the formation of the imidoylamidine
      complexes trans-[PtCl4{NH=C(R)N=C(Ph)NHPh}2] (1-4) isolated in good yields (66
      84%). The reaction of soluble complexes 3 and 4 with 2 equiv of Ph3P=CHCO2Me in
      CH2Cl2 (40 degrees C, 5 h) leads to dehydrochlorination resulting in a chelate
      ring closure to furnish the platinum(IV) chelates [PtCl2{NH=C(R)NC(Ph)=NPh}2] (R
      = Ph, 5; R = NEt2, 6), accordingly, and the phosphonium salt [Ph3PCH2CO2Me]Cl.
      Treatment of 5 with 3 equiv of Ph3P=CHCO2Me at 50 degrees C for 5 d resulted in
      only a 30% conversion to the corresponding Pt(II) complex
      [Pt{NH=C(NEt2)NC(Ph)=NPh}2] (15). The reduction can be achieved within several
      minutes, when Ph2PCH2CH2PPh2 in CDCl3 is used. When the platinum(II) complex
      trans-[PtCl2(RCN)2] is reacted with 2 equiv of the amidine, the imidoylamidinato
      complexes [PtCl(RCN){NH=C(R)NC(Ph)=NHPh}] (8-11) and [PhC(=NH)NHPh] x HCl (7) are
      formed. The reaction of trans-[PtCl2(RCN)2] with 4 equiv of the amidine under a
      prolonged reaction time or treatment of [PtCl(RCN){NH=C(R)NC(Ph)=NHPh}] (8-11)
      with 2 more equiv of the amidine yields the complex bearing two chelate rings
      [Pt{NH=C(R)NC(Ph)=NHPh}2] (12-15). The treatment of cis-[PtCl2(RCN)2] (R = Me,
      Et) with the amidine gives ca. 50-60% yield of [PtCl2{NH=C(R)NHC(Ph)=NHPh}] (16
      and 17). All of the platinum compounds were characterized by elemental analyses;
      FAB mass spectrometry; IR spectroscopy; 1H, 13C{1H}, and 195Pt NMR
      spectroscopies, and four of them (4, 6, 8, and 15) were also characterized by X
      ray crystallography. The coupling of the Pt-bound nitriles and the amidine is
      metal-mediated insofar as RCN and PhC(=NH)NHPh do not react in the absence of the
      metal centers in conditions more drastic than those of the observed reactions.
      The nitrile-amidine coupling reported in this work constitutes a route to the
      synthesis of imidoylamidine complexes, some of them exhibiting luminescent
      properties.

PMID- 15998046
TI  - Tuning tetranuclear manganese-oxo core electronic properties: adamantane-shaped
      complexes synthesized by ligand exchange.
AB  - A series of adamantane-shaped [Mn4O6]4+ aggregates has been prepared. Ligand
      substitution reactions of [Mn4O6(bpea)4](ClO4)4 (1) with tridentate amine and
      iminodicarboxylate ligands in acetonitrile affords derivative clusters
      [Mn4O6(tacn)4](ClO4)4 (4), [Mn4O6(bpea)2(dien)2](ClO4)4)(5),
      [Mn4O6(Medien)4](ClO4)4 (6), [Mn4O6(tach)4](ClO4)4 (7), [Mn4O6(bpea)2(me-ida)2]
      (8), [Mn4O6(bpea)2(bz-ida)2] (9), [Mn4O6(bpea)2((t)bu-ida)2] (10), and
      [Mn4O6(bpea)2((c)pent-ida)2] (11) generally on the order of 10 min with retention
      of core nuclearity and oxidation state. Of these complexes, only 4 had been
      synthesized previously. Characterization of two members of this series by X-ray
      crystallography reveals that compound 7 crystallizes as [Mn4O6(tach)4](ClO4)4 x
      3CH3CN x 4.5H2O in the cubic space group Fmm and compound 11 crystallizes as
      [Mn4O6(bpea)2((c)pent-ida)2].7MeOH in the monoclinic space group C2/c. The unique
      substitution chemistry of 1 with iminodicarboxylate ligands afforded
      asymmetrically ligated complexes 8-11, the mixed ligand nature of which is most
      likely unachievable using self-assembly synthetic methods. A special feature of
      the iminodicarboxylate ligand complexes 8-11 is the substantial site
      differentiation of the oxo bridges of the [Mn4O6]4+ cores. While there are four
      site-differentiated oxo bridges in 8, the solution structural symmetry of 8H+
      reveals essentially a single protonation isomer, in contrast to the observation
      of two protonation isomers for 1H+, one for each of the site-differentiated oxo
      bridges in 1. Magnetic susceptibility measurements on 4, 7, 8, and 9 indicate
      that each complex is overall ferromagnetically coupled, and variable-field
      magnetization data for 7 and 9 are consistent with an S = 6 ground state.
      Electrochemical analysis demonstrates that ligand substitution of bpea affords
      accessibility to the Mn(V)(Mn(IV))3 oxidation state.

PMID- 15998047
TI  - Water exchange from the oxo-centered rhodium(III) trimer [Rh3(mu3-O)(mu
      O2CCH3)6(OH2)3]+: a high-pressure 17O NMR study.
AB  - Water exchange from the oxo-centered rhodium(III) trimer, [Rh3(mu3-O)(mu
      O2CCH3)6(OH2)3]+, was investigated using variable-temperature (272.8-281.6 K) and
      variable-pressure (0.1-200 MPa) 17O NMR spectroscopy. The exchange reaction was
      also monitored at three different acidities (pH = 1.8, 2.9, and 5.7) in which the
      molecule is in the fully protonated form (pKa = 8.3 (+/-0.2), I = 0.1 M, T = 298
      K). The temperature dependence of the pseudo-first-order rate coefficient for
      water exchange yields the following kinetic parameters: k(ex)298 = 5 x 10(-3) s(
      1), deltaH(double dagger) = 99 (+/-3) kJ mol(-1), and deltaS(double dagger) = 43
      (+/-10) J K(-1) mol(-1). The enhanced reactivity of the terminal waters, some 6
      orders of magnitude faster than water exchange from Rh(H2O)6(3+), is likely due
      to trans-labilization from the central oxide ion. Also, another contributing
      factor is the low average charge on the metal ions (+0.33/Rh). Variation of
      reaction rate with pressure results in a deltaV(double dagger) = +5.3 (+/-0.4)
      cm3 mol(-1), indicative of an interchange-dissociative (I(d)) pathway. These
      results are consistent with those published by Sasaki et al. who proposed that
      water substitution from rhodium(III) and ruthenium(III) oxo-centered trimers
      follows a dissociative mechanism based on highly positive activation parameters
      (Sasaki, Y.; Nagasawa, A.; Tokiwa-Yamanoto, A.; Ito, T. Inorg. Chim. Acta 1993,
      212, 175-182).

PMID- 15998048
TI  - Effect of ligand structure on the pathways for iron release from human serum
      transferrin.
AB  - Rate constants for the removal of iron from N-terminal monoferric transferrin
      have been measured for a series of phosphate and phosphonocarboxylic acids in pH
      7.4 0.1 M hepes buffer at 25 degrees C. The bidentate ligands pyrophosphate and
      phosphonoacetic acid (PAA) show a combination of saturation and first-order
      kinetics with respect to the ligand concentration. Similar results are observed
      following a single substitution at the 2-position of PAA to give 2-benzyl-PAA and
      phosphonosuccinic acid. In contrast, disubstitution at the 2-position to form 2,2
      dibenzyl-PAA leads to a marked reduction in iron removal via the first-order
      pathway. Rate constants were also measured for tripolyphosphate and
      phosphonodiacetic acid, which are elongated versions of PP(i) and PAA. In both
      cases, this elongation completely eliminates the first-order component for iron
      release while having relatively little impact on the saturation pathway. The
      sensitivity of the first-order component to the structure of the ligand strongly
      indicates that this pathway involves the binding of the ligand to a specific site
      on the protein and cannot be attributed to changes in the overall ionic strength
      of the solution as the ligand concentration increases. It is proposed that this
      structural sensitivity reflects steric restrictions on the ability of the
      incoming ligand to substitute for the synergistic carbonate anion to form a
      relatively unstable Fe-ligand-Tf ternary intermediate, which then dissociates to
      FeL and apoTf.

PMID- 15998050
TI  - Bis(imino)pyridine iron(II) alkyl cations for olefin polymerization.
AB  - Treatment of the five-coordinate ferrous dialkyl complex, (iPrPDI)Fe(CH2SiMe3)2
      (iPrPDI = ((2,6-CHMe2)2C6H3N=CMe)2C5H3N), with [PhMe2NH][BPh4] in the presence of
      diethyl ether or tetrahydrofuran furnished the corresponding alkyl cations, where
      the donor ligand is coordinated in the basal plane of a distorted square
      pyramidal iron(II) alkyl cation. Performing the same reaction with the neutral
      Lewis acid, B(C6F5)3, induced methide abstraction from a silicon atom followed by
      rearrangement to afford the base free ferrous alkyl cation,
      [(iPrPDI)Fe(CH2SiMe2CH2SiMe3)][MeB(C6F5)3]. This complex is active for the
      polymerization of ethylene and yields polymers that are of higher molecular
      weight and narrower polydispersity than traditional methylalumoxane-activated
      catalysts.

PMID- 15998051
TI  - Phosphorylation of an alpha-synuclein peptide fragment enhances metal binding.
AB  - By using Tb3+ as a luminescent probe, we demonstrate that the phosphorylation
      state of a 14-residue peptide fragment of alpha-synuclein, a protein implicated
      in Parkinson's Disease, dramatically affects the metal ion affinity of the
      peptide. Whereas the unphosphorylated peptide and its phosphoserine analogue show
      weak Tb3+ binding, its phosphotyrosine analogue shows tight 1:1 binding as well
      as 2:1 and 3:1 Tb:peptide adducts. Our data suggest that the phosphorylated amino
      acid must be appropriately positioned among additional ligating residues to
      establish this phosphorylation-dependent metal binding.

PMID- 15998052
TI  - Expanding the conformational pool of cis-beta-sugar amino acid: accommodation of
      beta-hGly motif in robust 14-helix.
AB  - Tendencies of forming stable helices of heterooligomers composed of alternating
      rigid cis-beta-sugar amino acid and flexible beta-hGly motifs have been
      investigated, using a combination of molecular mechanics, CD, FT-IR, and NMR
      techniques. The results show that the solution structures of these oligomers
      exist as robust right-handed 14-helices. Here, we examine the role of
      conformationally rigid cis-beta-sugar amino acid in preorganizing the
      conformation of beta-hGly to form the 14-helix. Our findings also show that a
      right-handed 14-helix can be formed with as few as four properly sequenced
      heterogeneous residues. These results represent the expansion of the
      conformational pool of sugar amino acid in the design of well-folded 14-helices,
      which can be used to develop beta-peptides endowed with biological activity.

PMID- 15998053
TI  - Sensitive, label-free DNA diagnostics based on near-field microwave imaging.
AB  - Biological assays often rely on "reporter labels" to enhance measurement
      sensitivity, for example, by incorporation of a fluorescent dye or a nanoparticle
      into a nucleic acid or a protein. Use of labels, however, complicates sample
      preparation, increases assay costs, and can cause experimental artifacts by
      interfering with assay thermodynamics or limiting label stability. We evaluate
      near-field microwave imaging (NFMI) as an alternative, label-free technique for
      molecular diagnostics. Using DNA monolayers as an experimental model, NFMI is
      demonstrated to achieve sensitivities comparable to conventional fluorescence
      bioassays. Moreover, NFMI is shown to be compatible with imaging at resolutions
      required by microarray applications, as demonstrated by monitoring DNA
      hybridization in an array format.

PMID- 15998054
TI  - Helical nanofibers from aqueous self-assembly of an oligo(p-phenylene)-based
      molecular dumbbell.
AB  - We have synthesized an amphiphilic dumbbell-shaped molecule consisting of dodeca
      p-phenylene and aliphatic polyether dendrons as flexible end groups. The
      molecular dumbbell in aqueous solution self-assembles into well-defined left
      handed helical cylinders with a diameter (8 nm) of a molecular length scale and a
      pitch length of 5.6 nm, as confirmed by TEM. These elementary helical fibrils are
      further assembled to give left-handed superhelical fibers with lengths up to
      several micrometers. Such a well-defined helical arrangement of conjugated rod
      building blocks may provide a new strategy for the design of one-dimensional
      nanostructured materials with biomimetic, electronic, and photonic functions.

PMID- 15998055
TI  - Mechanism of DNA threading intercalation of binuclear Ru complexes: uni- or
      bimolecular pathways depending on ligand structure and binding density.
AB  - In the long succession of small transition-metal compounds interacting reversibly
      with DNA, semirigid binuclear ruthenium complexes stand out by displaying
      exceptionally slow binding kinetics. To reach the final intercalated state, one
      of the bulky metal centers has to be threaded through the base stack, leading to
      a high level of structural discrimination. This makes the idea of utilizing
      binuclear complexes interesting in applications involving DNA sequence or
      conformation recognition. The finding that threading intercalation of the two
      structural analogues, Lambda,Lambda-[mu-(11,11'-bidppz)X4Ru2]4+, X = 2,2'
      bipyridine (Lambda,Lambda-B4) and X = 1,10'-phenanthroline (Lambda,Lambda-P4),
      into poly(dA-dT)2 can be described by surprisingly simple rate laws encouraged
      more extensive studies and analysis of these two systems. Kinetic measurements at
      different [basepair]/[complex] ratios show that Lambda,Lambda-B4 intercalates via
      a pseudo-first-order mechanism independent of binding density, whereas
      Lambda,Lambda-P4 displays a gradual transition from apparent first- to second
      order kinetics when decreasing the [basepair]/[complex] mixing ratio. By
      employing the probabilistic method of McGhee and von Hippel, a rate law based on
      a supposed mechanism has been globally fitted and numerically integrated to
      describe threading of Lambda,Lambda-P4. In contrast to Lambda,Lambda-B4, the
      first-order mechanism of this analogue appears to require a long stretch of
      nonthreaded DNA. The results show that ancillary ligand structures indeed affect
      the mechanism of DNA threading, demonstrating the potential use of semirigid
      binuclear ruthenium complexes to target DNA.

PMID- 15998056
TI  - Using microfluidics to observe the effect of mixing on nucleation of protein
      crystals.
AB  - This paper analyzes the effect of mixing on nucleation of protein crystals. The
      mixing of protein and precipitant was controlled by changing the flow rate in a
      plug-based microfluidic system. The nucleation rate inversely depended on the
      flow rate, and flow rate could be used to control nucleation. For example, at
      higher supersaturations, precipitation happened at low flow rates while large
      crystals grew at high flow rates. Mixing at low flow velocities in a winding
      channel induces nucleation more effectively than mixing in straight channels. A
      qualitative scaling argument that relies on a number of assumptions is presented
      to understand the experimental results. In addition to helping fundamental
      understanding, this result may be used to control nucleation, using rapid chaotic
      mixing to eliminate formation of precipitates at high supersaturation and using
      slow chaotic mixing to induce nucleation at lower supersaturation.

PMID- 15998057
TI  - An acidic layered clay is combined with a basic layered clay for one-pot
      sequential reactions.
AB  - A Ti4+-exchanged montmorillonite (Ti4+-mont) and a hydrotalcite (HT) are strong
      solid Bronsted acid and base, and these two clay catalysts could be used in a
      single reactor without neutralization of active sites. Because the Ti4+-mont have
      active acid site in the narrow interlayers, the base sites of large HT particles
      show no interaction with the acid sites. A variety of acid and base reactions,
      such as esterification, acetalization, deacetalization, aldol reaction, Michael
      reaction, and epoxidation, proceeded using both the Ti4+-mont and the HT in a
      single reactor.

PMID- 15998058
TI  - The contact interface of a 120 kD CheA-CheW complex by methyl TROSY interaction
      spectroscopy.
AB  - During bacterial chemotaxis, the histidine autokinase CheA interacts with the
      chemotaxis receptors with the help of the coupling protein CheW. This interaction
      is typical of many macromolecular complexes where protein-protein interactions
      play an important role. In this case, a relatively small protein, CheW, becomes
      part of a much larger complex. Here we describe a new method to map the residues
      at a protein-protein interface for macromolecular complexes of molecular weight
      greater than 100 kD.

PMID- 15998059
TI  - Reversible holographic grating formation in polymer solutions.
AB  - We demonstrate the reversible optical recording of holographic gratings in
      nonabsorbing solutions of common homopolymers. These phase gratings exhibit first
      order diffraction efficiencies in excess of 50%. They are associated with the
      spatial modulation of the concentration of the polymer solute initiated, but not
      solely caused, by radiation forces.

PMID- 15998060
TI  - A heteronuclear bidentate Lewis acid as a phosphorescent fluoride sensor.
AB  - Reaction of dimesityl-1,8-naphthalenediylborate (1) with C6F5HgCl results in the
      formation of a B/Hg heteronuclear bidentate Lewis acid (2), which complexes
      fluoride to afford [2-mu2-F]-. Structural and photophysical studies carried out
      in solution and in the solid state indicate that 2 is a highly selective and
      sensitive phosphorescent fluoride sensor. The proximity of the two Lewis acidic
      sites enforced by the 1,8-naphthalenediyl backbone promotes fluoride anion
      chelation and is, therefore, responsible for the high binding constant. The
      interplay of conjugative and spin-orbit coupling effects mediated by the boron
      and mercury atoms, respectively, results in the phosphorescent signaling of
      fluoride binding. Remarkably, fluoride binding occurs in partially aqueous
      solutions and results in a drastic change of the phosphorescence observed when
      the solutions are frozen.

PMID- 15998061
TI  - Catalytic, enantioselective, conjugate alkyne addition.
AB  - We document a copper-catalyzed, enantioselective, conjugate addition involving
      the direct use of a terminal acetylene, which undergoes in situ metalation. The
      addition reactions of phenylacetylene to Meldrum's acid derived acceptors take
      place in aqueous media, without recourse to inert atmosphere. The success of the
      enantioselective process was enabled by the use of a new class of conveniently
      accessed P,N-ligands, which we have termed PINAP. These modular ligands are
      responsive to numerous electronic and steric modifications that permit
      optimization of the reaction.

PMID- 15998062
TI  - Missing metallofullerene La@C74.
AB  - The first isolation of missing metallofullerene, La@C74, as a derivative is
      reported. The structural determination has been performed by spectroscopic and,
      finally, X-ray crystallographic analysis, and the properties of La@C74 are
      discussed on the basis of the theoretical study.

PMID- 15998063
TI  - As a whole: crystalline zinc aluminate nanotube array--nanonet.
AB  - A large-area crystalline zinc aluminate nanotube array on its own nanonet was
      prepared by thermal replication on an anodized aluminum oxide template and
      through the gas-solid reaction between Zn vapor, Al2O3, and residual O2 or
      produced H2O. The free-standing nanotube array plus the nanonet structure, as a
      whole, was at least 900 mum2 in area. Each nanotube, 70-80 nm in diameter, was
      seamlessly connected to an underlying pore in the nanonet and was about 800 and
      15 nm in length and wall thickness, respectively. The nanonet was about 20 nm
      thick. Both the ZnAl2O4 nanotube and nanonet were in face-centered cubic crystal
      form and grew along the [12] direction.

PMID- 15998064
TI  - High elongation of polyelectrolyte chains in the osmotic limit of spherical
      polyelectrolyte brushes: a study by cryogenic transmission electron microscopy.
AB  - We investigate the conformation of long polyelectrolyte chains attached to
      colloidal latex particles by cryogenic transmission electron microscopy (cryo
      TEM). The dense grafting of the polyelectrolyte chains ("polyelectrolyte brush")
      leads to a confinement of the counterions and a concomitantly high osmotic
      pressure within the polyelectrolyte layer attached to the core particles. Cryo
      TEM has provided first model-independent direct proof for the strong stretching
      of the polyelectrolyte chains by direct visualization. If salt is added, cryo-TEM
      clearly shows how chains collapse because of the strong screening of the
      electrostatic interaction. Moreover, the analysis of interacting particles by
      cryo-TEM shows that the polyelectrolyte chains retract at close contact. Hence,
      we demonstrate how cryo-TEM can be used to analyze directly the spatial structure
      of polyelectrolyte brushes in situ.

PMID- 15998065
TI  - On the origin of the thermostabilization of proteins induced by sodium phosphate.
AB  - The B1 domain of protein L shows a linear rise in thermostability with increasing
      concentrations of sodium phosphate. Equal behavior is observed for a set of
      mutant proteins where surface lysines are mutated to noncharged residues, but the
      mutant's thermostabilities show different sensitivities to phosphate, encoded in
      the varying slopes observed (mi). The melting temperature in the absence of the
      cosolute also correlates linearly with mi. The stabilizing effect of the
      phosphate ion reaches a saturation point, which has been experimentally
      determined for protein L (1610 mM phosphate). These results indicate that the
      phosphate-induced stabilization is an inherent property of the protein, encoded
      in the amino acid sequence. Changes in stability upon mutation are attributed to
      a redistribution of the overall network of solvated surface charges.
      Stabilization by phosphate is understood in terms of interactions with the
      protein surface, reducing the unfavorable contacts between like charges,
      maximizing the number of accessible conformations of the surface-charged side
      chains, and optimizing solvation.

PMID- 15998066
TI  - Highly efficient endoglycosidase-catalyzed synthesis of glycopeptides using
      oligosaccharide oxazolines as donor substrates.
AB  - A highly efficient chemoenzymatic synthesis of N-glycopeptides was achieved. It
      was found that using synthetic oligosaccharide oxazolines, the mimics of the
      presumed oxazolinium ion intermediate formed in a retaining mechanism of
      substrate-assisted catalysis, as the donor substrates and GlcNAc-peptides as the
      acceptors, the endo-beta-N-acetylglucosaminidase (ENGase)-catalyzed
      transglycosylation gave a high yield (73-82%) of the corresponding glycopeptides
      in a regio- and stereospecific manner, regardless of the size of the peptide
      portions. The use of the oligosaccharide oxazolines as donor substrates not only
      expanded the substrate availability but also led to a substantial enhancement of
      the synthetic efficiency, compared to the use of natural N-glycans.

PMID- 15998067
TI  - Rhodium nanoparticles stabilized by ionic copolymers in ionic liquids: long
      lifetime nanocluster catalysts for benzene hydrogenation.
AB  - Novel ionic liquid-soluble ionic copolymers containing imidazolium ionic
      liquidlike units have been synthesized. Rhodium nanoparticles stabilized by the
      ionic copolymer in ionic liquids have been successfully obtained. The
      nanoparticles showed unprecedented lifetime and activity in arene hydrogenation
      under forcing conditions (a temperature of 75 degrees C and a hydrogen pressure
      of 40 bar) with a total turnover (TTO) of 20 000 (in five total recycles of 4000
      TTOs each) and a turnover frequency of 250 h-1, demonstrating that the
      combination of ionic liquids with ionic liquidlike stabilizers is a pathway
      towards highly stable and active nanoparticle catalysts.

PMID- 15998068
TI  - Bis(triarylmethylium)-mediated diaryl ether synthesis: oxidative arylation of
      phenols with N,N-dialkyl-4-phenylthioanilines.
AB  - Various aryl 4-dialkylaminophenyl ethers were readily synthesized without heating
      in good yield from phenols and N,N-dialkyl-4-phenylthioanilines. This oxidative
      arylation of phenols was successfully promoted by a
      bis(diphenylmethylium)naphthalenediyl dication via ipso-substitution of the
      phenylthio group in the anilines through a radical process.

PMID- 15998069
TI  - Nanoparticulate metal complexes prepared with compressed carbon dioxide:
      correlation of particle morphology with precursor structure.
AB  - Nanoparticles of metal complexes are rare because of the limited methods for
      their preparation. Described in this communication is the use of precipitation
      with compressed antisolvent (PCA) to process nanoparticles of neutral metal-salen
      complexes. PCA is a semicontinuous technique utilizing supercritical carbon
      dioxide (scCO2) as the precipitant. The scCO2 dissolves into a solution of the
      complex and simultaneously extracts the solvent, resulting in formation of
      nanoparticles of uniform morphology. Spectroscopic and analytical methods were
      used to support the assignment that the nanoparticles are composed of metal
      complexes. Scanning electron microscopy reveals that planar complexes, such as
      [NiIIsalen], afford rodlike particles with average diameter and length of 85 and
      700 nm, respectively. Complexes with nonplanar molecular structures produce
      nanoparticles with varied structures; for instance, PCA of the six-coordinate
      [Ru(salen)(NO)(Cl)] complex yields spherical nanoparticles with average diameters
      of 50 nm. These findings suggest a correlation between the structures of
      molecular precursors and the morphology of the processed particles, which
      possibly could be used as a bottom-up approach to the preparation of functional
      nanoparticles.

PMID- 15998070
TI  - Single peptide bonds exhibit poly(pro)II ("random coil") circular dichroism
      spectra.
AB  - The far-UV circular dichroism spectra of a series of amino acid derivatives
      containing single peptide bonds have been measured. The N-acetyl-alanine displays
      a polyproline (PP) II-like spectrum, but alaninamide shows a very weak positive
      signal. Similarly Gly-Ala shows a PPII spectrum, but Ala-Gly does not. On
      heating, the spectrum shows a two-state transition also shown by long PPII
      polypeptides. Thus the characteristic PPII negative maximum at <200 nm results
      from the coupling of a peptide bond N-terminal to the chiral alpha-carbon, and
      therefore the simplest peptide bonds have a preferred conformation that defines
      the spectrum of disordered proteins of any size.

PMID- 15998071
TI  - Conformationally gated electron transfer in iso-1-cytochrome c: engineering the
      rate of a conformational switch.
AB  - An engineered form of iso-1-cytochrome c with lysine 73 mutated to histidine is
      shown to increase by nearly 500-fold the rate of a conformational gate that
      modulates the rate of electron transfer into this protein. This result
      demonstrates the potential of protein engineering to provide electron transfer
      gates with tailored properties. The pH dependence of the rate of the
      conformational electron transfer gate correlates well with the pH dependence of
      the conformational change from a His 73-ligated heme to a Met 80-ligated heme,
      determined independently by pH jump methods, allowing unambiguous assignment of
      the conformational electron transfer gating step. The rate of the electron
      transfer gate is also modulated by a cis to trans proline isomerization,
      indicating that both amino acid sequence and the nature of the heme ligand
      provide avenues for rational design of electron transfer gates which open at
      different rates.

PMID- 15998072
TI  - Mobius aromaticity in [12]annulene: cis-trans isomerization via twist-coupled
      bond shifting.
AB  - Density functional and coupled cluster calculations show that facile thermal
      configuration change in [12]annulene occurs via a twist-coupled bond-shifting
      mechanism. The transition state for this process is highly aromatic with Mobius
      topology. At the CCSD(T)/cc-pVDZ//BH&HLYP/6-311+G** level, the isomerization of
      tri-trans-[12]annulene 1a (CTCTCT) to its di-trans isomer 2 (CCCTCT) via such a
      mechanism has a barrier of 18.0 kcal/mol, in good agreement with earlier
      experiments. Two other aromatic Mobius bond-shifting transition states were
      located that result in configuration change for other [12]annulene conformers.
      This mechanism contrasts sharply with diradical configuration change for acyclic
      polyenes and with planar bond-shifting mechanisms generally assumed for
      annulenes. This constitutes evidence that neutral Mobius aromatic annulenes play
      a role in the dynamic processes of neutral [4n]annulenes.

PMID- 15998073
TI  - Palladium-catalyzed intramolecular selenocarbamoylation of alkynes with
      carbamoselenoates: formation of alpha-alkylidene-beta-lactam framework.
AB  - Pd-catalyzed intramolecular selenocarbamoylation of alkynes leading to alpha
      alkylidene-beta-lactams was developed. This reaction can be applied to
      thiocarbamoylation and to the synthesis of delta- and epsilon-lactams and a
      cyclobutanone.

PMID- 15998074
TI  - Gold(I)-catalyzed ring expansion of cyclopropanols and cyclobutanols.
AB  - The rearrangement of 1-alkynyl cyclobutanols and cyclopropanols to alkylidene
      cycloalkanones catalyzed by cationic triarylphosphine gold(I) complexes is
      described. The reaction tolerates terminal alkynes as well as alkyl, aryl, and
      halo-substitution at the acetylenic position and stereoselectively provides a
      single olefin isomer. The gold(I)-catalyzed rearrangement is stereospecific with
      regard to substituents on the ring, thus providing a practical method for the
      stereoselective synthesis of highly substituted cyclopentanones from
      cyclopropanols. The reaction stereoselectively provides a single olefin isomer
      and is stereospecific with regard to substituents on the ring via sequential
      gold(I)-catalyzed ring expansion reactions.

PMID- 15998075
TI  - Design, synthesis, linear, and nonlinear optical properties of conjugated
      (porphinato)zinc(II)-based donor-acceptor chromophores featuring nitrothiophenyl
      and nitrooligothiophenyl electron-accepting moieties.
AB  - An extensive series of conjugated (porphinato)zinc(II)-based chromophores
      featuring nitrothiophenyl and nitrooligothiophenyl electron-accepting moieties
      has been synthesized using metal-catalyzed cross-coupling reactions involving [5
      bromo-15-triisopropylsilylethynyl-10,20-diarylporphinato]zinc(II) and an unusual
      electron-rich Suzuki-porphyrin synthon, [5-(4-dimethylaminophenylethynyl)-15
      (4',4',5',5'-tetramethyl[1',3',2']dioxaborolan-2'-yl)-10,20
      diarylporphinato]zinc(II), with appropriately functionalized aryl and thienyl
      precursors. These donor-acceptor chromophores feature thiophenyl,
      [2,2']bithiophenyl, and [2,2';5',2' ']terthiophenyl units terminated with a 5
      nitro group; one series of structures features these acceptor moieties appended
      directly to the porphyrin macrocycle meso-carbon position, while a second set
      utilizes an intervening meso-ethynyl moiety to modify porphyrin-to-thiophene
      conjugation. The dynamic hyperpolarizability of these compounds was determined
      from hyper-Rayleigh light scattering (HRS) measurements carried out at
      fundamental incident irradiation wavelengths (lambda(inc)) of 800 and 1300 nm;
      interestingly, measured beta(1300) values ranged from 650 --> 4350 x 10(-30) esu.
      The combined linear and nonlinear optical properties of these compounds challenge
      the classical concept of the nonlinearity/transparency tradeoff in charge
      transfer chromophores: the magnitude of the molecular hyperpolarizability is
      observed to vary substantially despite approximately uniform ground-state
      absorptive signatures for a given porphyrin-to-thiophene linkage topology. These
      data show that these neutral dipolar molecules can express substantial beta(1300)
      values; such conjugated, electronically asymmetric porphyrin-thiophene
      chromophores may thus find utility for electrooptic applications at telecom
      relevant wavelengths.

PMID- 15998076
TI  - Structural analysis of hybrid titania-based mesostructured composites.
AB  - High-optical-quality titania-based mesostructured films with cubic or 2D
      hexagonal symmetry were fabricated by combining trifluoroacetate (TFA)-modified
      titanium precursors with amphiphilic triblock poly(ethylene oxide)-poly(propylene
      oxide)-poly(ethylene oxide) (PEO-PPO-PEO) copolymers. The distribution, dynamics,
      and local environments of the TFA-modified titania, PEO, and PPO components of
      the hybrid were investigated. IR/Raman spectroscopy, in situ small-angle X-ray
      scattering, and transmission electron microscopy studies indicate that TFA
      coordinates the titanium center and forms a stable complex that is subsequently
      organized by the block copolymer species into ordered mesostructures. Solid-state
      NMR (19)F-->(1)H cross-polarization, (13)C{(1)H} two-dimensional heteronuclear
      correlation, and (1)H relaxation techniques were used to determine that PEO is
      predominantly incorporated within the TFA-modified titania, and that PPO
      environments encompass both microphase separated regions and interfacial regions
      composed of mixed PPO and TFA-modified titania. NMR (19)F multiple-quantum spin
      counting measurements suggest that -CF(3) groups of the trifluoroacetate ligands
      do not form clusters but instead randomly distribute within the inorganic
      component of the hybrid.

PMID- 15998077
TI  - Direct control of the magnetic interaction between iron oxide nanoparticles
      through dendrimer-mediated self-assembly.
AB  - Cationic superparamagnetic iron oxide nanoparticles were assembled using a series
      of anionic polyamidoamine dendrimers. The resulting assemblies featured
      systematically increasing average interparticle spacing over a 2.4 nm range with
      increasing dendrimer generation. This increase in spacing modulated the
      collective magnetic behavior by effective lowering of the dipolar coupling
      between particles. The results obtained in these studies deviate from the
      predicted dependence of collective behavior on interparticle spacing, suggesting
      that a dense assembly of magnetically "free" particles can exist with a
      surprisingly small space between particles.

PMID- 15998078
TI  - Comparative study of acetic acid, methanol, and water adsorbed on anatase TiO2
      probed by sum frequency generation spectroscopy.
AB  - Sum frequency generation (SFG) vibrational spectroscopy is used to investigate
      the surface adsorption of three probe molecules-acetic acid, methanol, and water-
      on a film composed of nanoscale anatase TiO(2) particles. On the TiO(2) surface,
      only one adsorption mode, chemisorption, is observed for acetic acid. This is
      evidenced by one sharp SFG peak in the C-H region, which is stable with time and
      robust both to evacuation and to the addition of water. A Langmuir constant of
      (9.21 +/- 0.71) x 10(3) is determined from the adsorption isotherm. In the case
      of methanol adsorption, however, there are two adsorption modes, molecular
      physisorption and dissociative chemisorption. The corresponding SFG signals are
      stable with time but diminished with addition of water. Changes in the SFG
      features for methanol and for the methoxy species with addition of water and
      subsequent evacuation provide the first experimental proof of reversible
      hydroxylation and dehydroxylation at the TiO(2) surface. For water adsorption,
      only one mode, physisorption, is observed on the hydroxylated TiO(2) surface. The
      water adlayer is mobile, as is evidenced by variation of the water H-bonded SFG
      signal with time. Competitive adsorption among the three molecular probes is
      clearly resolved by in situ SFG measurements. The adsorption strength follows the
      order acetic acid (strongest), methanol, water (weakest). The adsorption order as
      well as the difference in response of methanol versus acetic acid adsorption to
      addition of water has direct implications for understanding TiO(2) photocatalysis
      as well as the surface modifications involved in TiO(2) photoelectrochemical
      solar cells and processes in TiO(2) nanomaterial synthesis and assembly.

PMID- 15998079
TI  - Linear artificial molecular muscles.
AB  - Two switchable, palindromically constituted bistable [3]rotaxanes have been
      designed and synthesized with a pair of mechanically mobile rings encircling a
      single dumbbell. These designs are reminiscent of a "molecular muscle" for the
      purposes of amplifying and harnessing molecular mechanical motions. The location
      of the two cyclobis(paraquat-p-phenylene) (CBPQT(4+)) rings can be controlled to
      be on either tetrathiafulvalene (TTF) or naphthalene (NP) stations, either
      chemically ((1)H NMR spectroscopy) or electrochemically (cyclic voltammetry),
      such that switching of inter-ring distances from 4.2 to 1.4 nm mimics the
      contraction and extension of skeletal muscle, albeit on a shorter length scale.
      Fast scan-rate cyclic voltammetry at low temperatures reveals stepwise oxidations
      and movements of one-half of the [3]rotaxane and then of the other, a process
      that appears to be concerted at room temperature. The active form of the bistable
      [3]rotaxane bears disulfide tethers attached covalently to both of the CBPQT(4+)
      ring components for the purpose of its self-assembly onto a gold surface. An
      array of flexible microcantilever beams, each coated on one side with a monolayer
      of 6 billion of the active bistable [3]rotaxane molecules, undergoes controllable
      and reversible bending up and down when it is exposed to the synchronous addition
      of aqueous chemical oxidants and reductants. The beam bending is correlated with
      flexing of the surface-bound molecular muscles, whereas a monolayer of the
      dumbbell alone is inactive under the same conditions. This observation supports
      the hypothesis that the cumulative nanoscale movements within surface-bound
      "molecular muscles" can be harnessed to perform larger-scale mechanical work.

PMID- 15998080
TI  - Probing intramolecular Forster resonance energy transfer in a naphthaleneimide
      peryleneimide-terrylenediimide-based dendrimer by ensemble and single-molecule
      fluorescence spectroscopy.
AB  - We report on the ensemble and single-molecule (SM) dynamics of Forster resonance
      energy transfer (FRET) in a multichromophoric rigid polyphenylenic dendrimer
      (triad) with spectrally different rylene chromophores featuring distinct
      absorption and emission spectra which cover the whole visible spectral range: a
      terrylenediimide (TDI) core, four perylenemonoimides (PMIs) attached at the
      scaffold, and eight naphthalenemonoimides (NMIs) at the rim. For FRET from PMI to
      TDI taking place with an efficiency of 99.5%, single triad molecules optically
      excited at 490 nm show fluorescence exclusively from the TDI side in the
      beginning of their emission. On 360-nm excitation, NMI chromophores transfer
      their excitation energy either directly or in a stepwise fashion to the core TDI,
      the latter case involving scaffold-substituted PMIs as intermediate acceptors.
      Indeed, SM experiments on 360-nm excitation evidence highly efficient FRET from
      NMI chromophores to the TDI core since individual triad molecules show
      fluorescence exclusively either from TDI or from an intermediate (oxidized)
      species but never from PMI. Because PMI and TDI are chromophores with high
      fluorescence quantum yields and high resistance to photobleaching compared to
      NMI, 360-nm excitation of a single triad molecule leads to bleaching of NMI
      chromophores with no chance for PMI to be observed. The spatial positioning and
      the spectral properties of the chosen rylene chromophores make this
      multichromophoric system an efficient light collector, able to capture light over
      the whole visible spectral range and to transfer it finally to the core TDI, the
      latter releasing it as red fluorescence.

PMID- 15998081
TI  - Synthesis and magnetic properties comparison of M-Cu(II) and M-VO(II) Schiff base
      porphyrazine complexes: what is the mechanism for spin-coupling?
AB  - Dimetallic Schiff base-porphyrazine (pz) compounds, denoted 1[M(1); M(2); R],
      have been prepared, where metal ion M(1) is incorporated into the pz core, and
      metal ion M(2) is bound to a bis(5-tert-butylsalicylidenimine) chelate built onto
      two amino nitrogens attached to the pz periphery; R is a solubilizing group
      (either propyl (Pr) or 3,4,5-trimethoxyphenyl (TMP)) attached to the remaining
      carbons of the pz periphery. The synthesis of 1[Cu; Cu; R], 1[Cu; VO; R], 1[ClMn;
      Cu; Pr], and 1[ClMn; VO; Pr] is discussed, the crystal structures of 1[Cu; Cu;
      TMP] and 1[ClMn; VO; Pr] are presented, and the magnetic properties of these
      compounds are compared. The pattern of ligand-mediated exchange coupling in these
      complexes is startling: for the Cu-M(2) complexes 1[Cu; VO; R] and 1[Cu; Cu; R],
      2 x 10(2) < or = |J(Cu-VO)/J(Cu-Cu)|; for the ClMn-M(2) complexes 1[ClMn; Cu; Pr]
      and 1[ClMn; VO; Pr], J(ClMn-VO)/J(ClMn-Cu) approximately 1/3, an inverse ratio
      from that of the Cu-M(2) complexes, but with lesser discrimination. This coupling
      pattern is explained in terms of a novel orientation relative to the M(1)-M(2)
      direction: the "square-planar" Schiff base ligand set of M(2) is rotated in-plane
      by 45 degrees relative to the effectively coplanar pz ligand set of M(1).

PMID- 15998082
TI  - Self-assembled monolayers and preorganization of organosilanes prior to surface
      grafting onto silica: a quantum mechanical study.
AB  - Quantum chemical calculations have been carried out on the grafting of chain
      organosilane compounds on SiO(2)-hydroxylated solid surfaces. It is shown that a
      single molecule interacting with the surface lies flat to it, inhibiting further
      homogeneous film growth. This adsorption exhibits two molecule/surface
      interactions: a covalent bond on one side of the molecule and a hydrogen bond on
      the other side. We then investigate the possible preorganization of the molecules
      before grafting due to the presence of water molecules either in the gas/liquid
      phase or near the surface. This gives rise to the formation of dimerized chains.
      We then demonstrate that this preorganization process prevents subsequent lying
      flat of the molecules to the substrate after grafting. Energetics and associated
      configurations of the overall deposition process are discussed in detail and
      provide new insights on the understanding of the formation of self-assembled
      homogeneous organic films on microelectronics-type substrates.

PMID- 15998083
TI  - Geminal 2JCCH spin-spin coupling constants as probes of the phi glycosidic
      torsion angle in oligosaccharides.
AB  - Two-bond (13)C-(1)H NMR spin-spin coupling constants ((2)J(CCH)) between C2 and
      H1 of aldopyranosyl rings depend not only on the relative orientation of
      electronegative substituents on the C1-C2 fragment but also on the C-O torsions
      involving the same carbons. The latter dependencies were elucidated theoretically
      using density functional theory and appropriate model pyranosyl rings
      representing the four relative configurations at C1 and C2, and a 2-deoxy
      derivative, to probe the relationship between (2)J(C2,H1) magnitude and sign and
      the C1-O1 (phi, phi) and C2-O2 (alpha) torsion angles. Related calculations were
      also conducted for the reverse coupling pathway, (2)J(C1,H2). Computed J
      couplings were validated by comparison to experimentally measured couplings.
      (2)J(CCH) displays a primary dependence on the C-O torsion involving the carbon
      bearing the coupled proton and a secondary dependence on the C-O torsion
      involving the coupled carbon. These dependencies appear to be caused mainly by
      the effects of oxygen lone pairs on the C-H and C-C bond lengths along the C-C-H
      coupling pathway. New parameterized equations are proposed to interpret
      (2)J(C1,H2) and (2)J(C2,H1) in aldopyranosyl rings. The equation for (2)J(C2,H1)
      has particular value as a potential NMR structure constraint for the C1-O1
      torsion angle (phi) comprising the glycosidic linkages of oligosaccharides.

PMID- 15998084
TI  - Azide-inhibited bacterial heme oxygenases exhibit an S = 3/2
      (dxz,dyz)3(dxy)1(dz2)1 spin state: mechanistic implications for heme oxidation.
AB  - The azide complexes of heme oxygenase from Pseudomonas aeruginosa (pa-HO) and
      Neisseriae meningitidis (nm-HO) have been studied with the aid of (1)H and (13)C
      NMR spectroscopy. These complexes have been shown to exist as an equilibrium
      mixture of two populations, one exhibiting an S = (1)/(2), (d(xy))(2)(d(xz),
      d(yz))(3) electron configuration and planar heme and a second with a novel S =
      (3)/(2), (d(xz), d(yz))(3)(d(xy))(1)(d(z)(2))(1) spin state and nonplanar heme.
      At physiologically relevant temperatures, the equilibrium shifts in the direction
      of the population exhibiting the latter electron configuration and nonplanar
      heme, whereas at temperatures approaching the freezing point of water, the
      equilibrium shifts in the direction of the population with the former electronic
      structure and planar heme. These findings indicate that the microenvironment of
      the distal pocket in heme oxygenase is unique among heme-containing proteins in
      that it lowers the sigma-donating (field strength) ability of the distal ligand
      and, therefore, promotes the attainment of heme electronic structures thus far
      only observed in heme oxygenase. When the field strength of the distal ligand is
      slightly lower than that of azide, such as OH(-) (J. Am. Chem. Soc. 2003, 125,
      11842), the corresponding complex exists as a mixture of populations with
      nonplanar hemes and electronic structures that place significant spin density at
      the meso positions. The ease with which these unusual heme electronic structures
      are attained by heme oxygenase is likely related to activation of meso carbon
      reactivity which, in turn, facilitates hydroxylation of a meso carbon by the
      obligatory ferric hydroperoxide intermediate.

PMID- 15998085
TI  - First-principles study of superabundant vacancy formation in metal hydrides.
AB  - Recent experiments have established the generality of superabundant vacancies
      (SAV) formation in metal hydrides. Aiming to elucidate this intriguing phenomenon
      and to clarify previous interpretations, we employ density-functional theory to
      investigate atomic mechanisms of SAV formation in fcc hydrides of Ni, Cu, Rh, Pd,
      Ag, Ir, Pt, and Au. We have found that upon H insertion, vacancy formation
      energies reduce substantially. This is consistent with experimental suggestions.
      We demonstrate that the entropy effect, which has been proposed to explain SAV
      formation, is not the main cause. Instead, it is the drastic change of electronic
      structure induced by the H in the SAV hydrides, which is to a large extent
      responsible. Interesting trends in systems investigated are also found: ideal
      hydrides of 5d metals and noble metals are unstable compared to the corresponding
      pure metals, but the SAV hydrides are more stable than the corresponding ideal
      hydrides, whereas opposite results exist in the cases of Ni, Rh, and Pd. These
      trends of stabilities of the SAV hydrides are discussed in detail and a general
      understanding for SAV formation is provided. Finally, we propose an alternative
      reaction pathway to generate a SAV hydride from a metal alloy.

PMID- 15998086
TI  - Conformational constraint as a means for understanding RNA-aminoglycoside
      specificity.
AB  - The lack of high RNA target selectivity displayed by aminoglycoside antibiotics
      results from both their electrostatically driven binding mode and their
      conformational adaptability. The inherent flexibility around their glycosidic
      bonds allows them to easily assume a variety of conformations, permitting them to
      structurally adapt to diverse RNA targets. This structural promiscuity results in
      the formation of aminoglycoside complexes with diverse RNA targets in which the
      antibiotics assume distinct conformations. Such differences suggest that
      covalently linking individual rings in an aminoglycoside could reduce its
      available conformations, thereby altering target selectivity. To explore this
      possibility, conformationally constrained neomycin and paromomycin analogues
      designed to mimic the A-site bound aminoglycoside structure have been synthesized
      and their affinities to the TAR and A-site, two therapeutically relevant RNA
      targets, have been evaluated. As per design, this constraint has minimal
      deleterious effect on binding to the A-site. Surprisingly, however, preorganizing
      these neomycin-class antibiotics into a TAR-disfavored structure has no
      deleterious effect on binding to this HIV-1 RNA sequence. We rationalize these
      observations by suggesting that the A-site and HIV TAR possess inherently
      different selectivities toward aminoglycosides. The inherent plasticity of the
      TAR RNA, coupled to the remaining flexibility within the conformationally
      constrained analogues, makes this RNA site an accommodating target for such
      polycationic ligands. In contrast, the deeply encapsulating A-site is a more
      discriminating RNA target. These observations suggest that future design of novel
      target selective RNA-based therapeutics will have to consider the inherent
      "structural" selectivity of the RNA target and not only the selectivity patterns
      displayed by the low molecular weight ligands.

PMID- 15998087
TI  - Functional single-wall carbon nanotube nanohybrids--associating SWNTs with water
      soluble enzyme model systems.
AB  - We succeeded in integrating single-wall carbon nanotubes (SWNTs), several water
      soluble pyrene derivatives (pyrene(-)), which bear negatively charged ionic
      headgroups, and a series of water-soluble metalloporphyrins (MP(8+)) into
      functional nanohybrids through a combination of associative van der Waals and
      electrostatic interactions. The resulting SWNT/pyrene(-) and SWNT/pyrene(
      )/MP(8+) were characterized by spectroscopic and microscopic means and were found
      to form stable nanohybrid structures in aqueous media. A crucial feature of our
      SWNT/pyrene(-) and SWNT/pyrene(-)/MP(8)(+) is that an efficient exfoliation of
      the initial bundles brings about isolated nanohybrid structures. When the
      nanohybrid systems are photoexcited with visible light, a rapid intrahybrid
      charge separation causes the reduction of the electron-accepting SWNT and,
      simultaneously, the oxidation of the electron-donating MP(8)(+). Transient
      absorption measurements confirm that the radical ion pairs are long-lived, with
      lifetimes in the microsecond range. Particularly beneficial are charge
      recombination dynamics that are located deep in the Marcus-inverted region. We
      include, for the first time, work devoted to exploring and testing FeP(8)(+) and
      CoP(8)(+) in donor-acceptor nanohybrids.

PMID- 15998089
TI  - Stepwise delivery of two methoxy groups of arylaldehyde acetals across the phenyl
      ring. Vacant site-controlled palladium catalysis.
AB  - A new catalytic cyclization of o-alkynylbenzaldehyde acetals 1 to the
      functionalized indenes 2 was found to be strictly controlled by the number of
      triphenylphosphine ligands on the Pd catalyst. Only complexes with three
      available coordination sites on Pd catalyze this reaction. Mechanistic study
      suggests that pi-coordination of Pd to the benzene ring is a key step controlled
      by the number of vacant coordination sites.

PMID- 15998088
TI  - Theoretical study of binding of metal-doped graphene sheet and carbon nanotubes
      with dioxin.
AB  - Using density functional theory, we have theoretically studied dioxin binding on
      a graphene sheet or carbon nanotubes (CNT), finding that they can be effective
      adsorbents for dioxin in the presence of calcium atoms. This is due to a
      cooperative formation of sandwich complexes of graphene sheet or (5,5) CNT
      through the interaction pi-Ca-pi with the total binding energy of more than 3 eV.
      This correlates with the band structure analysis, which indicates charge transfer
      from the carbon systems and calcium atoms to dioxin when the molecule binds to
      the metal-doped carbon systems. For CNT with small radii, the relative strength
      of CNT-dioxin interaction is dependent on their chiralities. Upon dioxin binding,
      a large increase in the electronic density of states near the Fermi level also
      suggests that they can be used for dioxin sensing. Fe-doped CNT is also found to
      bind dioxin strongly, revealing an important role played by remnants of metallic
      catalysts in the chemical properties of CNT.

PMID- 15998090
TI  - Reversible and persistent electrical bistability in single crystals of a self
      assembled pi-conjugated tetraaryl system: a submicrometer scale electrical
      characterization.
AB  - A new pi-conjugated electroactive 4,4'-bipyridinium that bears two pyridazone
      self-complementary units was prepared and characterized. The new system readily
      assembles and forms at least two stable charge-transfer crystalline structures
      having a thermal population of unpaired electrons. The crystals of one phase
      exhibit electrical bistability, displaying either high (ON) and low (OFF)
      conductivity, at the same applied bias, depending on the electrical history of
      the system. The relation between the supramolecular structure of the crystals and
      their electrical properties is also discussed.

PMID- 15998091
TI  - Synthesis and fundamental studies of (H3Ge)xSiH4-x molecules: precursors to
      semiconductor hetero- and nanostructures on Si.
AB  - The synthesis of the entire silyl-germyl sequence of molecules (H(3)Ge)(x)SiH(4)(
      )(x) (x = 1-4) has been demonstrated. These include the previously unknown
      (H(3)Ge)(2)SiH(2), (H(3)Ge)(3)SiH, and (H(3)Ge)(4)Si species as well as the
      H(3)GeSiH(3) analogue which is obtained in practical high-purity yields as a
      viable alternative to disilane and digermane for semiconductor applications. The
      molecules are characterized by FTIR, multinuclear NMR, mass spectrometry, and
      Rutherford backscattering. The structural, thermochemical, and vibrational
      properties are studied using density functional theory. A detailed comparison of
      the experimental and theoretical data is used to corroborate the synthesis of
      specific molecular structures. The (H(3)Ge)(x)SiH(4)(-)(x) family of compounds
      described here is not only of intrinsic molecular interest but also provides a
      unique route to a new class of Si-based semiconductors including epitaxial layers
      and coherent islands (quantum dots), with Ge-rich stoichiometries SiGe, SiGe(2),
      SiGe(3), and SiGe(4) reflecting the Si/Ge content of the corresponding precursor.
      The layers grow directly on Si(100) at unprecedented low temperatures of 300-450
      degrees C and display homogeneous compositional and strain profiles, low
      threading defect densities, and atomically planar surfaces circumventing entirely
      the need for conventional graded compositions or lift-off technologies. The
      activation energies of all Si-Ge hydride reactions on Si(100) (E(a) approximately
      1.5-2.0 eV) indicate high reactivity profiles with respect to H(2) desorption,
      consistent with the low growth temperatures of the films. The quantum dots are
      obtained exclusively at higher temperatures (T > 500 degrees C) and represent a
      new family of Ge-rich compositions with narrow size distribution, defect-free
      microstructures, and homogeneous, precisely tuned elemental content at the atomic
      level.

PMID- 15998092
TI  - Kinetics of proton release after flash photolysis of 1-(2-nitrophenyl)ethyl
      sulfate (caged sulfate) in aqueous solution.
AB  - The kinetics of proton release after laser photolysis of 1-(2-nitrophenyl)ethyl
      sulfate (caged sulfate) have been characterized by time-resolved absorbance and
      photoacoustic methods. The absorbance at approximately 400 nm is observed to rise
      with a biphasic behavior in which a prompt component (formation of the nitronic
      acid) is followed by a slower (tau approximately 63 +/- 6 ns) phase
      (deprotonation of the nitronic acid). The decay of this intermediate occurs with
      a lifetime which is affected by the pH of the solution and the laser pulse
      energy. In buffered aqueous solution at pH 7, 20 degrees C the aci-nitro decay
      rate is 18 +/- 4 s(-1). Protons are released to the solution with rate (1.58 +/-
      0.09) x 10(7) s(-1) at neutral pH from the nitronic acid intermediate. From the
      numerical analysis of the protonation kinetics of suitable pH indicators, we
      could estimate the pK(a) of the nitronic acid as 3.69 +/- 0.05. At acidic pH, a
      substantial fraction of the aci-nitro intermediate is in the protonated form and
      this leads to a biphasic release of protons, with the slower phase being
      characterized by an apparent rate constant strongly dependent on the pH. The
      strongly acidic character of the final photoproduct (sulfate ion) means that
      there is negligible buffering of photoreleased protons.

PMID- 15998093
TI  - Substituted carborane-appended water-soluble single-wall carbon nanotubes: new
      approach to boron neutron capture therapy drug delivery.
AB  - Substituted C(2)B(10) carborane cages have been successfully attached to the side
      walls of single-wall carbon nanotubes (SWCNTs) via nitrene cycloaddition. The
      decapitations of these C(2)B(10) carborane cages, with the appended SWCNTs
      intact, were accomplished by the reaction with sodium hydroxide in refluxing
      ethanol. During base reflux, the three-membered ring formed by the nitrene and
      SWCNT was opened to produce water-soluble SWCNTs in which the side walls are
      functionalized by both substituted nido-C(2)B(9) carborane units and ethoxide
      moieties. All new compounds are characterized by EA, SEM, TEM, UV, NMR, and IR
      spectra and chemical analyses. Selected tissue distribution studies on one of
      these nanotubes, {([Na(+)][1-Me-2-((CH(2))(4)NH-)-1,2
      C(2)B(9)H(10)][OEt])(n)(SWCNT)} (Va), show that the boron atoms are concentrated
      more in tumors cells than in blood and other organs, making it an attractive
      nanovehicle for the delivery of boron to tumor cells for an effective boron
      neutron capture therapy in the treatment of cancer.

PMID- 15998094
TI  - New polymorphs of ROY and new record for coexisting polymorphs of solved
      structures.
AB  - With six polymorphs coexisting at room temperature, 5-methyl-2-[(2
      nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) is the top system in the current
      Cambridge Structural Database (Feb. 2005) for the number of polymorphs of solved
      crystal structures. Here we report two new ROY polymorphs, Y04 and YT04, and the
      crystal structure of YT04. Y04 is a metastable polymorph that tends to
      crystallize first from a melt at room temperature, and YT04 is a product of solid
      state transformation of Y04. Despite its late discovery, YT04 is the densest
      among the polymorphs at 25 degrees C and likely the second most stable at 0 K.
      The conformation of ROY in YT04 is similar to those in the other two yellow
      polymorphs (Y and YN) but significantly different from those in the orange and
      red colored polymorphs (ON, OP, ORP, and R). Having escaped years of solution
      crystallization in several laboratories, Y04 and YT04 exemplify polymorphs that
      are likely missed by solvent-based screening and discovered through alternative
      routes.

PMID- 15998095
TI  - Computational studies of the thermal fragmentation of P-arylphosphiranes: have
      arylphosphinidenes been generated by this method?
AB  - CASSCF, CASPT2, CCSD(T), and (U)B3LYP electronic structure calculations have been
      performed in order to investigate the thermal fragmentation of P
      phenylphosphirane (1) to phenylphosphinidene (PhP) and ethylene. The calculations
      show that generation of triplet PhP via a stepwise pathway is 21 kcal mol(-1)
      less endothermic and has a 12 kcal mol(-1) lower barrier height than concerted
      fragmentation of 1 to give singlet PhP. The formation of singlet PhP via a
      concerted pathway is predicted to be stereospecific, whereas formation of triplet
      PhP is predicted to occur with complete loss of stereochemistry. However,
      calculations on fragmentation of anti-cis-2,3-dimethyl-P-mesitylphosphirane (cis
      1Me) to triplet mesitylphosphinidene (MesP) indicate that this reaction should be
      more stereospecific, in agreement with the experimental results of Li and Gaspar.
      Nevertheless, with a predicted free energy of activation of 42 kcal mol(-1), the
      formation of MesP from cis-1Me is not likely to have occurred in an uncatalyzed
      reaction at the temperatures at which this phosphirane has been pyrolyzed.

PMID- 15998096
TI  - Adsorption of water on reconstructed rutile TiO2(011)-(2 x 1): Ti=O double bonds
      and surface reactivity.
AB  - Recent combined experimental and theoretical studies (Beck et al., Phys. Rev.
      Lett. 2004, 93, 036104) have provided evidence for Ti=O double-bonded titanyl
      groups on the reconstructed rutile TiO(2)(011)-(2 x 1) surface. The adsorption of
      water on the same surface is now investigated to further probe the properties of
      these groups, as well as to confirm their existence. Ultraviolet photoemission
      experiments show that water is adsorbed in molecular form at a sample temperature
      of 110 K. At the same time, the presence of a 3sigma state in the photoemission
      spectra and work function measurements indicate a significant amount of hydroxyls
      within the first monolayer of water. At room temperature, scanning tunneling
      microscopy (STM) suggests that dissociated water is present, and about 30% of the
      surface active sites are hydroxylated. These findings are well explained by total
      energy density functional theory calculations and Car-Parrinello molecular
      dynamics simulations for water adsorption on the titanyl model of TiO(2)(011)-(2
      x 1). The theoretical results show that a mixed molecular/dissociative layer is
      the most stable configuration in the monolayer regime at low temperatures, while
      complete dissociation takes place at 250 K. The arrangement of the protonated
      mono-coordinated oxygens in the mixed molecular/dissociated layer is consistent
      with the observed short-range order of the hydroxyls in the STM images.

PMID- 15998098
TI  - Polyethylene chain growth on zinc catalyzed by olefin polymerization catalysts: a
      comparative investigation of highly active catalyst systems across the transition
      series.
AB  - Highly active transition metal ethylene polymerization catalysts across the
      transition series have been investigated for their ability to catalyze chain
      growth on zinc. In reactions of various catalysts with ZnEt(2), product
      distributions range from Schulz-Flory to Poisson, with several catalysts showing
      intermediate behavior. A statistical modeling program is introduced to correlate
      product distributions with the relative rates of propagation, chain transfer to
      zinc, and beta-H transfer. Six regimes have been identified, ranging from Schulz
      Flory to pure Poisson where chain transfer to metal is the only termination
      process, through to combined alkane/alkene distributions where beta-H transfer is
      competitive with chain transfer to metal. It is concluded that, while catalyzed
      chain growth (CCG) is favored by a reasonable match between the bond dissociation
      energies of both the main group and transition metal alkyl species, the M-C bond
      energies of the bridging alkyl species, and hence the stabilities of any hetero
      bimetallic intermediates or transition states, are key. The latter are strongly
      influenced by the steric environment around the participating metal centers, more
      bulky ligands leading to a weakening of the bonds to the bridging alkyl groups;
      CCG is thus usually more favored for sterically hindered catalysts.

PMID- 15998097
TI  - C-H activation by a mononuclear manganese(III) hydroxide complex: synthesis and
      characterization of a manganese-lipoxygenase mimic?
AB  - Lipoxygenases are mononuclear non-heme metalloenzymes that regio- and
      stereospecifically convert 1,4-pentadiene subunit-containing fatty acids into
      alkyl peroxides. The rate-determining step is generally accepted to be hydrogen
      atom abstraction from the pentadiene subunit of the substrate by an active
      metal(III)-hydroxide species to give a metal(II)-water species and an organic
      radical. All known plant and animal lipoxygenases contain iron as the active
      metal; recently, however, manganese was found to be the active metal in a fungal
      lipoxygenase. Reported here are the synthesis and characterization of a
      mononuclear Mn(III) complex, [Mn(III)(PY5)(OH)](CF(3)SO(3))(2) (PY5 = 2,6
      bis(bis(2-pyridyl)methoxymethane)pyridine), that reacts with hydrocarbon
      substrates in a manner most consistent with hydrogen atom abstraction and
      provides chemical precedence for the proposed reaction mechanism. The neutral
      penta-pyridyl ligation of PY5 endows a strong Lewis acidic character to the metal
      center allowing the Mn(III) compound to perform this oxidation chemistry.
      Thermodynamic analysis of [Mn(III)(PY5)(OH)](2+) and the reduced product,
      [Mn(II)(PY5)(H(2)O)](2+), estimates the strength of the O-H bond in the metal
      bound water in the Mn(II) complex to be 82 (+/-2) kcal mol(-)(1), slightly less
      than that of the O-H bond in the related reduced iron complex,
      [Fe(II)(PY5)(MeOH)](2+). [Mn(III)(PY5)(OH)](2+) reacts with hydrocarbon
      substrates at rates comparable to those of the analogous [Fe(III)(PY5)(OMe)](2+)
      at 323 K. The crystal structure of [Mn(III)(PY5)(OH)](2+) displays Jahn-Teller
      distortions that are absent in [Mn(II)(PY5)(H(2)O)](2+), notably a compression
      along the Mn(III)-OH axis. Consequently, a large internal structural
      reorganization is anticipated for hydrogen atom transfer, which may be correlated
      to the lessened dependence of the rate of substrate oxidation on the substrate
      bond dissociation energy as compared to other metal complexes. The results
      presented here suggest that manganese is a viable metal for lipoxygenase activity
      and that, with similar coordination spheres, iron and manganese can oxidize
      substrates through a similar mechanism.

PMID- 15998099
TI  - Stereochemical memory effects in alkene radical cation/anion contact ion pairs:
      effect of substituents, and models for diastereoselectivity.
AB  - A series of 12 stereochemically defined 2,m-dimethyl- and 2,m,n-trimethyl-6
      benzylamino-2-nitro-3-(diphenylphosphatoxy)hexanes have been synthesized and
      their cyclization reactions leading to di- and trisubstituted N-benzyl
      pyrrolidines examined in the presence of tributyltin hydride and
      azoisobutyronitrile in benzene at reflux. The cyclizations are interpreted in
      terms of generation of an alkyl radical by abstraction of the nitro group with a
      stannyl radical. The phosphate leaving group is then expelled in a heterolytic
      cleavage to give a contact alkene radical cation/phosphate anion pair. For the
      majority of the examples studied, the cyclizations are best understood in terms
      of nucleophilic attack by the amine on the opposite face of the alkene radical
      cation to the one shielded by the leaving group, within the confines of the
      initial contact ion pair, resulting in overall cyclization with inversion of
      configuration. Dependent on the relative stereochemistry of the substituents, the
      cyclization is envisaged as taking place through either chair-like or twist-boat
      like transition states with the maximum number of substituents pseudo-equatorial.
      The model breaks down when cyclization on the initial contact ion pair would
      engender significant destabilizing steric interactions, especially (1,3)A strain
      in the alkene radical cation. In these cases a fully equilibrated Beckwith-Houk
      type transition state provides a satisfactory model. Interesting examples of
      matching and mismatching in the Corey-type oxazaborolidine-mediated reduction of
      alkyl (methyl-1-nitroethyl) ketones by a beta-methyl group in the alkyl chain are
      reported, and the mismatching is attributed to a developing syn-pentane
      interaction in the transition state.

PMID- 15998100
TI  - Theoretical considerations and computational analysis of the complexity in
      polyketide synthesis pathways.
AB  - The emergence of antimicrobial resistance has led to an increase in research
      directed toward the engineering of novel polyketides. To date, less than 10 000
      polyketide structures have been discovered experimentally; however, the
      theoretical analysis of polyketide biosynthesis performed suggests that over a
      billion possible structures can be synthesized. Polyketide synthesis, which
      involves the formation of a linear chain and its subsequent cyclization, is
      catalyzed by an enzyme complex called polyketide synthase (PKS). There are a
      number of variables in the linear chain synthesis controlled by the PKS: the
      number, identity, stereochemistry and sequence of the monomer units used in the
      elongation steps, and the degree of reduction that occurs after each of the
      condensation reactions. The theoretical analysis performed demonstrates that
      changes in these variables lead to the formation of different polyketide linear
      chains and, consequently, a high diversity of polyketide structures. The
      complexity in the number of possible structures led to the implementation of this
      system in BNICE, a computational framework that generates all possible
      biochemical pathways using a given set of enzyme reaction rules. This formulation
      allowed the analysis of the evolution of diversity in the synthesis mechanism and
      the construction of the pathway architecture of polyketide biosynthesis. It is
      expected that, after future implementation of the cyclization reactions, this
      framework can be used to identify all possible polyketides and their
      corresponding synthesis pathways. Consequently, this formulation would prove
      useful in guiding experimental approaches to engineer novel polyketides, a number
      of which will likely have medicinal properties.

PMID- 15998101
TI  - Utilization of an oxonia-Cope rearrangement as a mechanistic probe for Prins
      cyclizations.
AB  - An oxonia-Cope rearrangement was used as an internal clock reaction to probe the
      mechanism of the Prins cyclization reaction and the subsequent nucleophilic
      capture of the resultant tetrahydropyranyl cation. The oxonia-Cope rearrangement
      was shown to occur rapidly under typical Prins cyclization conditions when the
      oxocarbenium ion resulting from the rearrangement is similar to or lower in
      energy than the starting oxocarbenium ion. Oxonia-Cope rearrangements can be
      disfavored by destabilizing the resultant oxocarbenium ion or by stabilizing an
      intermediate tetrahydropyranyl cation. Stereoselectivity in the nucleophilic
      capture was dramatically affected by the reactivity of the nucleophile and
      electrophile. More reactive partners combined rapidly to give axial-substituted
      Prins products through a least-motion pathway. High selectivity for the
      equatorial-substituted tetrahydropyran was observed for less reactive
      nucleophiles and electrophiles.

PMID- 15998103
TI  - Quantitative analysis of the 26 allergens for cosmetic labeling in fragrance raw
      materials and perfume oils.
AB  - The adoption of the 7th amendment of the European Cosmetic Directive 76/768/EEC
      requires any cosmetic product containing any of 26 raw materials identified by
      the Scientific Committee on Cosmetic Products and Non-Food Products intended for
      Consumers as likely to cause a contact allergy when present above certain trigger
      levels to be declared on the package label. Of these 26, 24 are volatile and can
      be analyzed by GC. This paper describes a method for the quantitative analysis of
      these volatile raw materials in perfume ingredients as well as complex perfume
      compositions. The method uses sequential dual-column GC-MS analysis. The full
      scan data acquired minimize the false-positive and false-negative identifications
      that can be observed with alternate methods based on data acquired in the SIM
      mode. For each sample, allergen levels are determined on both columns
      sequentially, leading to two numerical results for each allergen. Quantification
      limits for each allergen in a perfume mixture based on the analysis of a standard
      are <4 mg/kg. This is well below the level that would trigger label declaration
      on the consumer good. Calibration curves for all allergens are linear (r > 0.999)
      and stable for multiple days. Studies on perfumes spiked with multiple allergens
      at 30, 50, and 70 mg/kg show recoveries close to nominal values.

PMID- 15998104
TI  - Development of an extractive spectrophotometric method for the determination of
      copper(II) in leafy vegetable and pharmaceutical samples using pyridoxal-4-phenyl
      3-thiosemicarbazone (PPT).
AB  - A highly sensitive extractive spectrophotometric method has been developed for
      the determination of copper(II) using pyridoxal-4-phenyl-3-thiosemicarbazone(PPT)
      as an analytical reagent. The PPT forms reddish brown species of copper(II) at a
      pH range of 3.0-5.5, and the complex was extracted into n-butanol. The Cu(II)-PPT
      complex shows maximum absorbance at 440 nm, with molar absorptivity and Sandell's
      sensitivity being 2.16 x 10(4) L mol(-1) cm(-1) and 2.94 x 10(-3) microg cm(-2),
      respectively. The system obeys Beer's law in the range of 0.2-5.0 mg/L. The
      regression coefficient of the Beer's law straight line is 0.338, and the
      correlation coefficient is 0.96. The detection limit of the method is 0.0065
      microg mL(-1). Most of the common metal ions generally found associated with
      copper do not interfere. The repeatability of the method was checked by finding
      the relative standard deviation. The developed method has been successfully
      employed for the determination of copper(II) in leafy vegetable and
      pharmaceutical samples. The method is evaluated by analyzing samples from the
      Bureau of Analyzed Samples (BCS 233, 266, 216/1, 207, and 179) and by
      intercomparison of experimental values using AAS.

PMID- 15998105
TI  - SPME-GC-pyrolysis-AFS determination of methylmercury in marine fish products by
      alkaline sample preparation and aqueous phase phenylation derivatization.
AB  - Characterization of a cost-efficient analytical method based on alkaline sample
      digestion with KOH and NaOH, followed by aqueous phase phenylation derivatization
      with NaBPh4 and solid phase microextraction (SPME) for the determination of
      methylmercury in typical fish-containing food samples commercially available in
      Hungary, is reported. The sample preparation procedure along with the applied
      SPME-GC-pyrolysis-AFS system was validated by measuring certified reference
      materials (CRM) BCR-464, TORT-2, and a candidate CRM BCR 710. To carry out an
      estimation of average Hungarian methylmercury exposures via marine fish and/or
      fish-containing food consumption, 16 commercially available products and 3 pooled
      representative seafood samples of-according to a previous European survey--the
      three most consumed fish species in Hungary, herring, sardines, and hake, were
      analyzed. Methylmercury concentrations of the analyzed samples were in the range
      0.016-0.137 microg of MeHg g(-1) dry weight as Hg.

PMID- 15998106
TI  - Total lipid extraction of homogenized and intact lean fish muscles using
      pressurized fluid extraction and batch extraction techniques.
AB  - The reliability and efficiency of pressurized fluid extraction (PFE) technique
      for the extraction of total lipid content from cod and the effect of sample
      treatment on the extraction efficiency have been evaluated. The results were
      compared with two liquid-liquid extraction methods, traditional and modified
      methods according to Jensen. Optimum conditions were found to be with 2
      propanol/n-hexane (65:35, v/v) as a first and n-hexane/diethyl ether (90:10, v/v)
      as a second solvent, 115 degrees C, and 10 min of static time. PFE extracts were
      cleaned up using the same procedure as in the methods according to Jensen. When
      total lipid yields obtained from homogenized cod muscle using PFE were compared
      yields obtained with original and modified Jensen methods, PFE gave significantly
      higher yields, approximately 10% higher (t test, P < 0.05). Infrared and NMR
      spectroscopy suggested that the additional material that inflates the gravimetric
      results is rather homogeneous and is primarily consists of phospholipid with
      headgroups of inositidic and/or glycosidic nature. The comparative study
      demonstrated that PFE is an alternative suitable technique to extract total lipid
      content from homogenized cod (lean fish) and herring (fat fish) muscle showing a
      precision comparable to that obtained with the traditional and modified Jensen
      methods. Despite the necessary cleanup step, PFE showed important advantages in
      the solvent consumption was cut by approximately 50% and automated extraction was
      possible.

PMID- 15998107
TI  - Development of competitive direct ELISA for gossypol analysis.
AB  - Anti-gossypol monoclonal antibody was purified from cell culturing supernatant by
      ammonium sulfate precipitation and Protein A AffinityPak. The antigen (i.e.,
      gossypol) was labeled with horseradish peroxidase through Schiff-base formation.
      Both the purified antibody and the enzyme-labeled gossypol were employed to
      develop a competitive direct enzyme-linked immunosorbent assay (cdELISA) for
      gossypol analysis. I50 value, the concentration of gossypol causing 50%
      inhibition of the maximum ELISA signal in the competitive standard curve, was
      0.067 microg/mL, whereas the detection limit for gossypol was 0.005 microg/mL. We
      also observed a good correlation (R2= 0.96, P < 0.05) between the cdELISA method
      and the AOCS official method for "free" gossypol (extractable gossypol and
      gossypol derivatives by 70% acetone) analysis of cottonseed meals. This indicates
      that the newly developed cdELISA could be a valuable and feasible alternative for
      determination of "free" gossypol, especially when the available sample is limited
      with relatively low gossypol concentration.

PMID- 15998108
TI  - Automated on-line solid-phase extraction-liquid chromatography-electrospray
      tandem mass spectrometry method for the determination of ochratoxin A in wine and
      beer.
AB  - An automated on-line solid-phase extraction-liquid chromatography-electrospray
      tandem mass spectrometry (SPE-LC-ESI-MS/MS) method was developed for the
      determination of ochratoxin A (OTA) in alcoholic beverages. Mean recoveries for
      wine and beer were, respectively, 75 and 82%. Detection was achieved in negative
      ionization with a Q TRAP mass spectrometer operating in multiple-reaction
      monitoring (MRM) mode or enhanced product ion (EPI) mode, using the third
      quadrupole as linear ion trap. The MRM mode turned out to be more sensitive; the
      method allowed accurate determination of OTA in the range of 0.01-25 ng mL(-1)
      using external calibration. Within-day and between-day relative standard
      deviation percentages were <6.2 and <9.1%, respectively. In EPI mode,
      fragmentation spectra at the limit of quantification (0.03 ng mL(-1)) and good
      linearity could be obtained. Application of the method (MRM mode) to the analysis
      of several wine and beer samples purchased in local stores revealed OTA levels in
      the ranges of 0.03-1.44 ng mL(-1) for wines and 0.02-0.14 ng mL(-1) for beers.

PMID- 15998109
TI  - Radical scavenging capacity of wine anthocyanins is strongly pH-dependent.
AB  - The radical scavenging capacity of red wine anthocyanins was quantified by the so
      called TEAC assay with special emphasis on the influence of pH and conjugation on
      this activity. The pH appears to be a dominant factor in the radical scavenging
      capacity of wine anthocyanins, with higher pH values increasing this capacity
      significantly. On the basis of the pKa values for deprotonation and theoretical
      calculations, it could be concluded that the effect is due to an increase in
      intrinsic radical scavenging capacity upon deprotonation. The data also reveal
      that the reduction in radical scavenging activity of anthocyanins upon their
      conjugation can, at least in part, be ascribed to an increase in pKa values upon
      conjugation. Altogether, the results obtained provide molecular insight into
      factors that influence radical scavenging potential of anthocyanins and reveal
      that the radical scavenging-mediated supposed beneficial health effects of these
      wine pigments will be influenced by the pH of the surrounding matrix or tissue.

PMID- 15998110
TI  - Phytochemicals in broccoli transcriptionally induce thioredoxin reductase.
AB  - Previous studies have demonstrated transcriptional induction of thioredoxin
      reductase (TR) by sulforaphane (SF) purified from broccoli; the mechanism of
      induction is via an antioxidant response element (ARE) in the promoter region of
      the gene. The purpose of the present study was to further characterize the
      induction of TR by compounds in broccoli and to determine if SF is the primary
      compound responsible for this induction. Aqueous extracts were made from broccoli
      with low or high concentrations of selenium (Se) and/or SF and tested in a
      TR/luciferase reporter gene system in cultured cells. Phenolic acids commonly
      found in broccoli (sinapic, caffeic, ferulic, and protocatechuic) and ascorbic
      acid were also tested. At SF concentrations of < or =2 microM, broccoli extracts
      and purified SF activated transcription equally well, but 4 microM SF in broccoli
      extracts resulted in almost twice as much induction as 4 microM purified SF (P <
      0.05). All broccoli extracts significantly increased TR and quinone reductase
      activity relative to controls (P < 0.05), but only extracts highest in Se
      increased glutathione peroxidase activity (P < 0.05). No phenolic acids tested
      induced transcription, but ascorbic acid resulted in modest dose-dependent
      induction between 0 and 120 microM (P < 0.001). These data suggest that SF
      accounts for most of the ARE-activated transcriptional induction of antioxidant
      genes by broccoli.

PMID- 15998111
TI  - Ethanol and polyphenolic free wine matrix stimulate the differentiation of human
      intestinal Caco-2 cells. Influence of their association with a procyanidin-rich
      grape seed extract.
AB  - The effect of daily contact with ethanol on Caco-2 cell differentiation was
      investigated. Pure ethanol (1%) and a polyphenolic free wine matrix (polyphenol
      free wine containing 1% ethanol) associated or not with a procyanidin-rich grape
      seed extract (GSE) were added to Caco-2 cells from confluency for 2 h a day after
      successive incubation in salivary, gastric, and pancreatic media. Treatment with
      1% ethanol did not appear to be cytotoxic to cells, but it also stimulated Caco-2
      cell differentiation, particularly in the first days following confluency, and
      this effect was more marked when associated with polyphenolic free wine matrix
      constituents. This activation resulted in an increase in microvillar density,
      organization, and elongation (+70%) and was associated with strong stimulation of
      sucrase-isomaltase (+780%) and a concomitant regular increase in cell protein
      content (+50-88%). While the presence of GSE in alcoholic solutions did not
      modify the morphological pattern observed in cells subjected to ethanol and
      polyphenolic free wine matrix alone, it had a clear reducing effect on their
      microvillus elongation (-30%). However, these stimulating effects of ethanol on
      morphological differentiation were attenuated from day 10 postconfluency, which
      could suggest cell cytoprotection against ethanol. These are the first results in
      support of the notion that moderate concentration of ethanol may stimulate the
      differentiation of Caco-2 cells, particularly when integrated with a polyphenolic
      free wine matrix.

PMID- 15998112
TI  - Larvicidal and adulticidal activity of alkylphthalide derivatives from rhizome of
      Cnidium officinale against Drosophila melanogaster.
AB  - The insecticidal activity of the chloroform extract of Cnidium officinale
      rhizomes and its constituents was investigated against larvae and adults of
      Drosophila melanogaster and compared with that of rotenone. Bioassay-guided
      isolation of the chloroform extract of C. officinale resulted in the isolation
      and characterization of four alkylphthalides, cnidilide (1), (Z)-ligustilide (2),
      (3S)-butylphthalide (3), and neocnidilide (4). The structures of these compounds
      were established by spectroscopic analysis. The isolated compounds 2, 3, and 4
      exhibited LC50 values of 2.54, 4.99, and 9.90 micromol/mL of diet concentration
      against larvae of D. melanogaster, respectively. Against both sexes
      (males/females, 1:1) of adults (5-7 days old), compound 3 showed the most potent
      activity of the compounds isolated with the LD50 value of 5.93 microg/adult,
      comparable to that of rotenone (LD50 = 3.68 microg/adult). Structure-activity
      relationships of phthalides isolated suggest that the presence of conjugation
      with the carbonyl group in the lactone ring appeared to play an important role in
      the larvicidal activity. Acetylcholinesterase (prepared from the adult heads of
      D. melanogaster) inhibitory activity was also investigated in vitro to determine
      the insecticide mode of action for the acute adulticidal activity.

PMID- 15998113
TI  - Structural and biological characterization of aminated-derivatized oat beta
      glucan.
AB  - beta-Glucan extracted from oats was subjected to reductive amination, producing a
      cationic beta-glucan derivative of which physiological properties were
      characterized. The degree of substitution was obtained from elemental analysis,
      which was 0.48. In addition, the distribution of amino groups in the beta-glucan
      derivative was investigated by FT-IR analysis. In vitro bile acid binding
      capacity of the aminated beta-glucan was examined, showing significantly higher
      bile acid binding activity than native beta-glucan. Moreover, the beta-glucan
      derivative showed pronounced antimicrobial effects against Escherichia coli and
      Bacillus subtilis, and ACE (angiotensin-converting enzyme) inhibition activities
      which were dependent on its concentration. Furthermore, bronchoalveolar lavage
      (BAL) experiments demonstrated that the beta-glucan derivative stimulated the
      synthesis of nitric oxide. The improved functionalities of the derivative could
      be explained by its polycationic characteristics.

PMID- 15998114
TI  - Mycelia from Antrodia camphorata in Submerged culture induce apoptosis of human
      hepatoma HepG2 cells possibly through regulation of Fas pathway.
AB  - The objective of this study was to investigate the antiproliferative effect and
      the mechanism of the methanol extracts of mycelia (MEM) form Antrodia camphorata
      in submerged culture toward HepG2 cells. The results showed that MEM-induced cell
      apoptosis involved up-regulation of Fas and down-regulation of Bcl-2, DR3, DR4,
      TNFRI, and TNFRII in HepG2 cells, while no changes on the levels of Bax, Bid,
      Bad, and Bak protein were observed. On the basis of these results, the
      involvement of the Fas/Fas ligand (FasL) death-receptor pathway, in MEM-induced
      apoptosis in HepG2 cells, was investigated. The apoptosis inducing activity was
      significantly enhanced by a Fas activator and inhibited by a Fas antagonist. To
      know about the effect of MEM on the activation of the apoptotic pathway, the
      adenovirus transfected with Bcl-2 was infected on HepG2 cells. The data showed
      that the percentage of apoptotic cells induced by MEM in Bcl-2-infected HepG2
      (Bcl-2 overexpression) was not significantly different from that of uninfected
      HepG2. These results demonstrate that MEM induces HepG2 apoptosis through
      inhibition of cell growth and up-regulation of Fas/FasL to activate the pathway
      of caspase-3 and -8 cascades.

PMID- 15998115
TI  - Role of chitinase and sormatin accumulation in the resistance of sorghum
      cultivars to grain mold.
AB  - Experiments were conducted to determine the association between resistance to
      grain mold and the accumulations of chitinase and sormatin. Eight sorghum lines
      were treated at 50% bloom with Fusarium thapsinum, Curvularia lunata, a mixture
      of the two fungi, and a water-sprayed control. At maturity, percent disease
      severity, seed germination rates, and kernel weight were recorded. Chitinase and
      sormatin content (mg/g of dry weight) were measured in seed samples taken at 30
      and 50 days after treatment (DAT). Seed chitinase content was moderately affected
      by sorghum line (P = 0.10) and significantly affected by the developmental stage
      of the kernels (P = 0.05). Cultivars Sureno, 98LB650, and 98LB723 exhibited
      larger negative changes in chitinase content at 50 DAT over water-sprayed control
      treatment at 30 DAT than the susceptible cultivars Dorado, RTx2536, and RTx430.
      In 2000, significant negative correlations were observed for percent disease
      severity and chitinase content at 30 DAT, seed germination and sormatin content
      at 50 DAT, and between seed germination and kernel weight. There also was a
      significant positive correlation between germination and chitinase content at 30
      DAT. No association between disease severity and changes in chitinase content at
      50 DAT was observed. Sormatin content also was significantly affected by the
      stage of kernel development. Sorghum cultivars inoculated with fungal pathogens
      responded differently as indicated by the significant sorghum line x treatment
      interaction for sormatin content in 2000. In both years, larger increases in
      sormatin content over the water-sprayed control treatments were observed on
      moderately susceptible to susceptible cultivars such as 98LB650, 98LB723,
      98LB789, RTx430, and RTx2536 than on Sureno. Except for percent disease severity
      and germination, there was no significant association among all of the other
      parameters measured in 2001. The results of this study did not clearly
      demonstrate a strong association between resistance to grain mold and the
      accumulation of sormatin and chitinase. Thus, there is the possibility that
      certain moderately resistant to resistant sorghum cultivars, such as Sureno, may
      employ other strategies to eschew or restrict fungal invasion either before or
      after physiological maturity.

PMID- 15998116
TI  - Identification of urolithin a as a metabolite produced by human colon microflora
      from ellagic acid and related compounds.
AB  - Dietary ellagic acid and related polyphenols are metabolized in humans to
      dibenzopyran-6-one derivatives, and the microbial origin of these metabolites has
      been suggested. However, this has not been demonstrated so far. Fecal samples
      donated by six volunteers were incubated under anaerobic conditions, and aliquots
      were used to evaluate the fecal metabolism of ellagic acid, the ellagitannin
      punicalagin, and an ellagitannin rich extract from walnuts. The isoflavone
      daidzein was also incubated with the same fecal samples to follow the production
      of the microbial metabolites previously reported (dihydrogenistein, O
      demethylangolensin, and equol) as a positive control of the system and to
      evaluate similarities between isoflavone and ellagic acid fecal flora metabolism.
      After fermentation the metabolite "urolithin A" (3,8-dihydroxy-6H
      dibenzo[b,d]pyran-6-one) was produced from ellagic acid, punicalagin, and the
      ellagitannin extract in all the fecal cultures from different volunteers, but
      with very different production rates and concentrations. This large variability
      in the concentration of metabolite and kinetics of metabolite production is
      consistent with the large variability found in the excretion of these metabolites
      in urine in vivo after human consumption of ellagitannins, and with differences
      in the composition of the fecal microflora. No correlation between isoflavone and
      ellagic acid metabolism by fecal microflora was observed. The present study
      confirms the microbial origin of the recently reported in vivo generated hydroxy
      6H-dibenzo[b,d]pyran-6-one derivatives in humans and is a further step in the
      study of the bioavailability and metabolism of ellagic acid and ellagitannins.

PMID- 15998117
TI  - Radical scavenging and anti-lipoperoxidative activities of Smallanthus
      sonchifolius leaf extracts.
AB  - Radical scavenging and anti-lipoperoxidative effects of two organic fractions and
      two aqueous extracts from the leaves of a neglected Andean crop-yacon
      (Smallanthus sonchifolius Poepp. & Endl., Asteraceae) were determined using
      various in vitro models. The extracts' total phenolic content was 10.7-24.6%.
      They exhibited DPPH (IC50 16.14-33.39 microg/mL) and HO* scavenging activities
      (4.49-6.51 mg/mL). The extracts did not scavenge phenylglyoxylic ketyl radicals,
      but they retarded their formation. In the xanthine/xanthine oxidase superoxide
      radical generating system, the extracts' activities were 26.10-37.67 superoxide
      dismutase equivalents/mg. As one of the extracts displayed xanthine oxidase
      inhibitory activity, the effect of the extracts on a nonenzymatically generated
      superoxide was determined (IC50 7.36-21.01 microg/mL). The extracts inhibited t
      butyl hydroperoxide-induced lipoperoxidation of microsomal and mitochondrial
      membranes (IC50 22.15-465.3 microg/mL). These results make yacon leaves a good
      candidate for use as a food supplement in the prevention of chronic diseases
      involving oxidative stress.

PMID- 15998118
TI  - Policosanol contents and compositions of wheat varieties.
AB  - Policosanol (PC) is the common name for a mixture of high molecular weight (20-36
      carbon) aliphatic primary alcohols, which are constituents of plant epicuticular
      waxes. Wheat germ oil has been reported to improve human physical fitness, and
      this effect is attributed to its high PC, specifically its high octacosanol (OC)
      content. Although the PC composition of wheat leaves has been studied
      extensively, information on PC content and composition of wheat grain fractions
      is scarce. The objective of this study was to examine the PC contents and
      compositions of wheat grain fractions of 31 varieties grown in Oklahoma. PC
      compositions of the samples were identified using a gas chromatograph coupled
      with a mass spectrometer. The PC content of wheat bran was higher than that of
      the germ, shorts, and flour. The Trego and Intrada varieties had the highest PC
      content among the 31 wheat varieties studied. Tetracosanol (C24), hexacosanol
      (C26), and OC (C28) were the major PC components in all varieties. This study
      showed that wheat varieties grown under identical growing conditions and
      management differ significantly in PC content and composition.

PMID- 15998119
TI  - Characterization of squid-processing byproduct hydrolysate and its potential as
      aquaculture feed ingredient.
AB  - The squid (Loligo pealei) byproduct composed of heads, viscera, skin, fins, and
      small tubes was subjected to hydrolysis at 55 degrees C and natural pH (6.8)
      using endogenous proteases. Squid hydrolysate was characterized during the course
      of hydrolysis for changes in the degree of hydrolysis, viscosity, electrophoretic
      pattern of proteins and peptides, and amino acid and fatty acid profiles. The
      change in viscosity can be used to monitor the progress of protein hydrolysis up
      to the molecular mass of 26.63 kDa. The 2 h hydrolysis resulted in a 2-fold
      increase in the total free amino acids and yielded hydrolysate with protein
      molecular mass of < or =45 kDa having feed attractability and good amino acid and
      fatty acid profiles with high contents of essential amino acids and fatty acids.
      Such hydrolysis-induced changes can make squid byproduct hydrolysate a good
      source of aquaculture feed ingredient, especially for a starter diet for larval
      fish.

PMID- 15998120
TI  - Isolation and characterization of phytoene desaturase cDNA involved in the beta
      carotene biosynthetic pathway in Dunaliella salina.
AB  - The green alga Dunaliella salina is one of the best and most important biological
      sources of beta-carotene; however, to date the molecular basis of the beta
      carotene biosynthesis process in D. salina is still unresolved. The
      dehydrogenation of phytoene is the second step in the carotenoids biosynthetic
      pathway, and the phytoene-related desaturases are the key enzymes in the beta
      carotene biosynthetic pathway. A phytoene desaturase (Pds) cDNA with a 1752 bp
      open reading frame was cloned by RT-PCR and RACE-PCR methods on the basis of a
      modified switching mechanism at 5' end of the RNA transcript (SMART) technology
      from D. salina. The predicted protein sequence displays a high identity (up to
      65%) with phytoene desaturases of higher plants and cyanobacteria. The highest
      amino acid sequence identity (91%) is shared with the phytoene desaturase
      sequence of Dunaliella bardawil, and a dinucleotide-binding motif lies in the N
      terminal. The phylogenetic analysis shows that D. salina Pds is closer to higher
      plants and cyanobacteria than bacterial and fungi. These results together
      demonstrated the cloned Pds cDNA of D. salina is a Pds-type gene, and it is
      postulated that in D. salina the first two dehydrogenations, by which phytoene is
      converted into zeta-carotene, are carried out by this putative phytoene
      desaturase.

PMID- 15998121
TI  - Genetic manipulation for enhancing calcium content in potato tuber.
AB  - Increased calcium (Ca) in potatoes may increase the production rate by enhancing
      tuber quality and storability. Additionally, increased Ca levels in important
      agricultural crops may help ameliorate the incidence of osteoporosis. However,
      the capacity to alter Ca levels in potato tubers through genetic manipulations
      has not been previously addressed. Here we demonstrate that potato tubers
      expressing the Arabidopsis H+/Ca2+ transporter sCAX1 (N-terminal autoinhibitory
      domain truncated version of CAtion eXchanger 1) contain up to 3-fold more Ca than
      wild-type tubers. The increased Ca appears to be distributed throughout the
      tuber. The sCAX1-expressing potatoes have normally undergone the
      tuber/plant/tuber cycle for three generations; the trait appeared stable through
      successive generations. The expression of sCAX1 does not appear to alter potato
      growth and development. Furthermore, increased Ca levels in sCAX1-expressing
      tubers do not appear to alter tuber morphology or yield. Given the preponderance
      of potato consumption worldwide, these transgenic plants may be a means of
      marginally increasing Ca intake levels in the population. To our knowledge, this
      study represents the first attempts to use biotechnology to increase the Ca
      content of potatoes.

PMID- 15998122
TI  - Potential application of ribosomal intergenic spacer analysis to the microbial
      community analysis of agronomic products.
AB  - Ribosomal intergenic spacer analysis (RISA) has been applied to the microbial
      community analysis of agronomic products in combination with a simple and rapid
      DNA extraction method, consisting of a one-step extraction and two-step
      purification, for a variety of agronomic products. RISA appears to be a useful
      tool for the study of the community structures of food-associated microbes and
      their use as a unique fingerprinting signature for each agronomic product.
      Sequencing analyses of amplicons generated from RISA suggest that this method can
      detect conventional microbes. In the case of RISA of wasabi paste DNA, the
      sequences of the amplicons showed high similarity to the plant pathogen
      Xanthomonas campestris and the soil bacterium Bacillus subtilis, whereas several
      food-associated bacteria (Lactococcus lactis, Lactococcus raffinolactis, and
      Lactococcus sakei) were detected using this technique in sausage DNA.
      Unexpectedly, the sequencing analyses also revealed the presence of several
      microbes that possessed high similarity to human bacterial pathogens such as
      Weissella confusa and Yersinia pestis. The results suggest that RISA will be a
      useful method for routine microbial community analysis in agronomic products.

PMID- 15998123
TI  - Functional expression in pichia pastoris of an acidic pectin methylesterase from
      jelly fig (Ficus awkeotsang).
AB  - A cDNA fragment encoding an acidic pectin methylesterase (PME) of jelly fig
      achene was successfully expressed in Pichia pastoris under the control of the
      glyceraldehydes-3-phosphate dehydrogenase promoter. The recombinant PME was
      produced as a secretory protein by N-terminal fusion of a cleavable prepropeptide
      for signal trafficking, and thus easily harvested from the culture medium.
      Compared with native N-glycosylated PME (38 kDa) purified from jelly fig achenes,
      this recombinant PME (45 kDa) appeared to be hyperglycosylated. Activity staining
      indicated that the recombinant PME was functionally active. Yet the
      hyperglycosylated recombinant PME possessed thermostability and enzymatic
      capability over a broad pH range equivalent to those of the native PME. The
      success of functional production of this acidic jelly fig PME in P. pastoris has
      significantly broadened its applications in industry.

PMID- 15998124
TI  - Enzymatic interesterification of butterfat with rapeseed oil in a continuous
      packed bed reactor.
AB  - Lipase-catalyzed interesterification of butterfat blended with rapeseed oil
      (70/30, w/w) was investigated both in batch and in continuous reactions. Six
      commercially available immobilized lipases were screened in batch experiments,
      and the lipases, Lipozyme TL IM and Lipozyme RM IM, were chosen for further
      studies in a continuous packed bed reactor. TL IM gave a fast reaction and had
      almost reached equilibrium with a residence time of 30 min, whereas RM IM
      required 60 min. The effect of reaction temperature was more pronounced for RM
      IM. TL IM showed little effect on the interesterification degree when the
      temperature was raised from 60 degrees C to 90 degrees C, whereas RM IM had a
      positive effect when the temperature was increased from 40 degrees C to 80
      degrees C. Even though TL IM is an sn-1,3 specific lipase, small changes in the
      sn-2 position of the triacylglycerol could be seen. The tendency was toward a
      reduction of the saturated fatty acid C14:0 and C16:0 and an increase of the long
      chain saturated and unsaturated fatty acids (C18:0 and C18:1), especially at
      longer residence times (90 min). In prolonged continuous operation the activity
      of TL IM was high for the first 5 days, whereafter it dramatically decreased over
      the next 10 days to an activity level of 40%. In general, the study shows no
      significant difference for butterfat interesterification in terms of enzyme
      behavior from normal vegetable oils and fats even though it contains short-chain
      fatty acids and cholesterol. However, the release of short-chain fatty acids from
      enzymatic reactions makes the sensory quality unacceptable for direct edible
      applications.

PMID- 15998125
TI  - Preventing lipid oxidation during recovery of functional proteins from herring
      (Clupea harengus) fillets by an acid solubilization process.
AB  - It has previously been found that a process based on solubilization at pH 2.7
      gives high yields of herring muscle proteins with good functionality. In this
      study, the development of lipid oxidation during acid processing of herring mince
      was studied. It was tested how modifications of the process conditions and/or
      additions of antioxidants could prevent lipid oxidation during the actual process
      and then during ice storage of the protein isolates. Processing parameters
      evaluated were prewash of the mince, exposure time to pH 2.7, inclusion or
      exclusion of a high-speed centrifugation, and addition of antioxidants.
      Antioxidants tested were erythorbate (0.2%, 9.3 mM), sodium tripolyphosphate
      (STPP; 0.2%, 5.4 mM), ethylenediaminetetraacetic acid (EDTA; 0.044%, 1.5 mM), and
      milk proteins (4%). The first three antioxidants were added in the prewash or
      during the homogenization step, whereas milk proteins were added to the final
      precipitate. At time 0, all isolates were analyzed for pH, moisture content, and
      thiobarbituric reactive substances (TBARS). Selected isolates were also analyzed
      for lipid and protein content. Stability during ice storage was followed in terms
      of odor, TBARS, and color (a/b values). Extensive lipid oxidation took place
      using the "control" process without high-speed centrifugation. This was not
      significantly (p < or = 0.05) affected by a prewash or varied exposure time to pH
      2.7. Including high-speed centrifugation (20 min, 10,000g) significantly (p < or
      = 0.05) reduced TBARS values, total lipids, a values and b values. Erythorbate
      alone, or in combination with STPP/EDTA, significantly (p < or = 0.05) reduced
      lipid oxidation during processing if added in the prewash or homogenization step.
      During ice storage, better stability was gained when antioxidants were added in
      both of these steps and when EDTA was used instead of STPP.

PMID- 15998126
TI  - Precipitation of cheddar cheese whey lipids by electrochemical acidification.
AB  - Lipid separation from cheddar cheese whey allows a better valorization of protein
      fractions. In this study, bipolar membrane electroacidification (BMEA) was used
      to obtain precipitates with a high level of lipids. Whey samples with normal and
      low (by way of electrodialysis) mineral salt levels have been treated by a BMEA
      process and centrifuged. The composition of flocs and precipitation yields were
      determined. The BMEA process increased lipid precipitation rates by almost 50% in
      comparison with a centrifugation step only whereas a demineralization step prior
      to electroacidification had a limited effect on the precipitation level.
      Precipitates obtained were mainly composed of lipids (probably phospholipids) but
      also contained proteins. BMEA of cheddar cheese whey would allow the production
      of a lipid-enriched fraction and of a protein-enriched whey.

PMID- 15998127
TI  - Processing strawberries to different products alters contents of vitamin C, total
      phenolics, total anthocyanins, and antioxidant capacity.
AB  - Strawberries were processed to juice, nectar, wine, and puree. For investigation
      of the antioxidant capacity as well as the contents of ascorbic acid, total
      phenolics and total anthocyanins, samples were taken after different stages of
      production to determine the effects of processing. The content of vitamin C was
      measured spectrophotometrically. The total phenolic content was analyzed by using
      the Folin-Ciocalteu method, and the amount of total anthocyanins was determined
      by using the pH-differential method. Two different methods-the trolox equivalent
      antioxidant capacity assay and the ferric reducing antioxidant power test-were
      used to determine the hydrophilic antioxidant capacity. This study showed the
      decrease of all investigated parameters within processing strawberries to
      different products. The content of ascorbic acid decreased with production time
      and processing steps, especially during heat treatment. The investigations on
      total phenolics in strawberry products proved fining to be a mild method to
      clarify berry juices and wines without removing high amounts of total phenolics.
      Fermentation did not lead to heavy losses of total phenolics, probably due to
      polymerization and condensation of monomer phenolics such as anthocyanins. Total
      anthocyanins and the hydrophilic antioxidant capacity decreased while using high
      temperatures. Anthocyanins also decreased considerably during the processing of
      wines, mainly caused by fermentation and pasteurization.

PMID- 15998128
TI  - Interactions between yeast lees and wine polyphenols during simulation of wine
      aging: I. Analysis of remnant polyphenolic compounds in the resulting wines.
AB  - Wine aging on yeast lees is a traditional enological practice used during the
      manufacture of wines. This technique has increased in popularity in recent years
      for the aging of red wines. Although wine polyphenols interact with yeast lees to
      a limited extent, such interactions have a large effect on the reactivity toward
      oxygen of wine polyphenolic compounds and yeast lees. Various domains of the
      yeast cell wall are protected by wine polyphenols from the action of
      extracellular hydrolytic enzymatic activities. Polysaccharides released during
      autolysis are thought to exert a significant effect on the sensory qualities of
      wine. We studied the chemical composition of polyphenolic compounds remaining in
      solution or adsorbed on yeast lees after various contact times during the
      simulation of wine aging. The analysis of the remnant polyphenols in the wine
      indicated that wine polyphenols adsorption on yeast lees follows biphasic
      kinetics. An initial and rapid fixation is followed by a slow, constant, and
      saturating fixation that reaches its maximum after about 1 week. Only very few
      monomeric phenolic compounds remained adsorbed on yeast lees, and no preferential
      adsorption of low or high polymeric size tannins occurred. The remnant condensed
      tannins in the wine contained fewer epigallocatechin units than the initial
      tannins, indicating that polar condensed tannins were preferentially adsorbed on
      yeast lees. Conversely, the efficiency of anthocyanin adsorption on yeast lees
      was unrelated to its polarity.

PMID- 15998129
TI  - Ozonated water extends the shelf life of fresh-cut lettuce.
AB  - The use of ozonated water as a sanitizer to extend the shelf life of fresh-cut
      lettuce and the effect on the antioxidant constituents (polyphenols and vitamin
      C) were investigated. Fresh-cut iceberg lettuce (Lactuca sativa L.) was washed at
      4 degrees C using three different ozonated water dips [10, 20, and 10 activated
      by ultraviolet C (UV-C) light mg L(-1) min total ozone dose], and the dips were
      compared with water and chlorine rinses. Treated lettuce was packaged in air or
      active modified atmosphere packaging (MAP) (4 kPa of O2 + 12 kPa of CO2 balanced
      with N2) and stored for 13 days at 4 degrees C. Despite its strong oxidizing
      activity, ozonated water did not stimulate the respiratory activity of fresh-cut
      lettuce. Moreover, ozonated water maintained the initial visual appearance of
      fresh-cut lettuce and controlled browning during storage in air. Initially,
      ozonated water and chlorine reduced the total mesophilic population by 1.6 and
      2.1 log, respectively, when compared with water. Active MAP was effective in
      controlling total microbial growth, achieving 2.0 log reduction in relation to
      samples stored in air at the end of storage. On the other hand, active MAP caused
      a 2.0-3.5 reduction of coliforms on sanitized samples compared with water-washed
      samples. The most efficient treatments were ozone 20 and ozone 10 activated by UV
      C, which were as effective as chlorine. Changes in individual phenolic compounds
      were independent of the washing treatments. In air, chlorogenic and
      isochlorogenic acid contents increased noticeably after 13 days while
      monocaffeoyltartaric and dicaffeoyltartaric acids remained unchanged. MAP
      effectively suppressed accumulation of caffeoylquinic derivatives, whereas
      caffeoyltartaric derivatives decreased during MAP storage to reach similar
      levels. The content of vitamin C (ascorbic acid and dehydroascorbic acid)
      decreased during storage, particularly under MAP. Ozonated water could be an
      alternative sanitizer to chlorine for fresh-cut lettuce due to good retention of
      sensorial quality and browning control with no detrimental reduction in the
      antioxidant constituents.

PMID- 15998130
TI  - Determination of stilbenes (delta-viniferin, trans-astringin, trans-piceid, cis-
      and trans-resveratrol, epsilon-viniferin) in Brazilian wines.
AB  - Phenolics from grapes and wines can play a role against oxidation and development
      of atherosclerosis. Stilbenes have been shown to protect lipoproteins from
      oxidative damage and to have cancer chemopreventive activity. We describe a
      method for the direct determination of stilbenes in several red wines using high
      performance liquid chromatography with UV detection. In a survey of 12 commercial
      wines from the south of Brazil (Rio Grande del Sul), levels of delta-viniferin
      are reported for the first time in different varieties of red wines. Brazilian
      red wine contains trans-astringin, trans-piceid, trans-resveratrol, cis
      resveratrol (in high quantity: 5 times more than the trans form), epsilon
      viniferin, and a compound isolated for the first time in wine, trans-delta
      viniferin. Isolation and identification of delta-viniferin was achieved by NMR
      after extraction and fractionation of red wine phenolics. delta-Viniferin
      contributes, as well as cis-resveratrol and trans-piceid, to a significant
      proportion of stilbenes in wine dietary intake, particularly with Merlot
      varieties containing an average level of 10 mg/L for delta-viniferin, 15 mg/L for
      cis-resveratrol, and 13 mg/L for trans-piceid. The total stilbene intake from
      wine origin was estimated for the Brazilian population as 5.3 mg/day per person
      (on the basis of a regular wine consumption of 160 mL/day). delta-Viniferin can
      contribute to around 20% of total stilbenes in wine (average of 6.4 mg/L in red
      Brazilian wines). It would be important in the future to investigate the origins
      of the differences in wine stilbene levels in relation to the vine varieties, and
      the bioavailability of the newly extracted stilbene delta-viniferin in plasma
      after consumption of different types of wines.

PMID- 15998131
TI  - Oxalate and phytate of soy foods.
AB  - The consumption of foods made from soybeans is increasing because of their
      desirable nutritional value. However, some soy foods contain high concentrations
      of oxalate and/or phytate. Oxalate is a component of calcium oxalate kidney
      stones, whereas phytate is an inhibitor of calcium kidney stone formation. Thirty
      tested commercial soy foods exhibited ranges of 0.02-2.06 mg oxalate/g and 0.80
      18.79 mg phytate/g. Commercial soy foods contained 2-58 mg of total oxalate per
      serving and 76-528 mg phytate per serving. Eighteen of 19 tofu brands and two
      soymilk brands contained less than 10 mg oxalate per serving, defined as a low
      oxalate food. Soy flour, textured vegetable soy protein, vegetable soybeans, soy
      nuts, tempeh, and soynut butter exhibited greater than 10 mg per serving. The
      correlation between oxalate and phytate in the soy foods was significant (r =
      0.71, P < 0.001) indicating that oxalate-rich soy foods also contain higher
      concentrations of phytate. There also was a significant correlation, based on
      molar basis, between the divalent ion binding potential of oxalate plus phytate
      and calcium plus magnesium (r = 0.90, P < 0.001) in soy foods. Soy foods
      containing small concentrations of oxalate and moderate concentrations of phytate
      may be advantageous for kidney stone patients or persons with a high risk of
      kidney stones.

PMID- 15998132
TI  - Adsorption-desorption dynamics of cyprodinil and fludioxonil in vineyard soils.
AB  - Cyprodinil and fludioxonil are new-generation fungicides that are employed to
      protect grapevines from botrytis and various rots. In this work, their adsorption
      and desorption dynamics in eight vineyard soils from Galicia (northwestern Spain)
      were examined in batch and column experiments. Both fungicides exhibited linear
      adsorption isotherms, with more ready adsorption (greater Kd) of fludioxonil. Kd
      values for cyprodinil were significantly correlated with soil organic matter
      content (r 2= 0.675, p < 0.01). Both pesticides exhibited adsorption-desorption
      hysteresis, but desorption was easier and more variable for cyprodinil (12-21%,
      RSD = 17%) than for fludioxonil (3-5%, RSD = 13%) and appeared to depend on the
      formation of irreversible bonds in the former case and on poor solubility in the
      latter. A linear adsorption model involving nonequilibrium conditions and an
      irreversible adsorption term was found to reproduce transport behavior
      accurately.

PMID- 15998133
TI  - Prediction of the wine sensory properties related to grape variety from dynamic
      headspace gas chromatography-olfactometry data.
AB  - Wine extracts obtained by a dynamic headspace sampling technique were studied by
      quantitative gas chromatography-olfactometry (GC-O) to determine the aroma
      profiles of six young monovarietal Spanish white wines. A partial least-square
      regression study was carried out to look for models relating wine aroma
      properties with GC-O scores. Models were validated by sensory analysis. Four out
      of the five most important sensory descriptors were satisfactorily described by a
      model, and sensory tests confirmed most of the predictions. The main aroma
      differences between these wines are due to the ratio linalool/3-mercaptohexyl
      acetate. Floral, sweet, and muscat are positively related to the concentration of
      linalool and negatively to that of 3-mercaptohexyl acetate. Tropical fruit is
      related to the wine content in this last odorant. 2-Phenyl acetate, reinforced by
      other acetates, can also contribute to floral and sweet notes. Alkyl
      methoxypyrazines lessen the tropical fruit note, and acetic acid lessens the
      muscat nuance.

PMID- 15998134
TI  - Purification and identification of linoleic acid hydroperoxides generated by
      soybean seed lipoxygenases 2 and 3.
AB  - It has been known that lipoxygenase (LOX) isozymes exhibit differences in product
      formation, but most product information to date is for LOX 1 among soybean
      (Glycine max) LOX isozymes. In this study, LOXs 2 and 3 were purified and used to
      generate hydroperoxide (HPOD) products in an in vitro system using linoleic acid
      as a substrate in the presence of either air or O2. The products were analyzed to
      determine their stereoisomeric characteristics. The control (no enzyme) showed
      only low levels of hydroperoxide production and no stereoisomeric specificity.
      LOX 2 shows high specificity in product formation, producing roughly 4 times more
      13-HPOD than 9-HPOD, nearly all of which was 13-S(Z,E)-HPOD. LOX 3 produced more
      9-HPOD than 13-HPOD at approximately a 2:1 ratio. No single stereoisomer was
      predominant among LOX 3 products. These results demonstrate that different
      isozymes of LOX have characteristic product profiles in in vitro reactions.

PMID- 15998135
TI  - The apoptotic effect of green tea (-)-epigallocatechin gallate on 3T3-L1
      preadipocytes depends on the Cdk2 pathway.
AB  - This study was designed to investigate the effect of green tea catechins,
      especially (-)-epigallocatechin gallate (EGCG), on the apoptosis of 3T3-L1
      preadipocytes. Preadipocyte apoptosis as indicated by formation of DNA fragments
      was induced by EGCG in dose-dependent manners. While EGCG was demonstrated to
      decrease Cdk2 expression and activity and increase caspase-3 activity,
      overexpression of Cdk2 and treatment with the caspase-3 inhibitor respectively
      prevented preadipocytes from induction of DNA fragmentation and caspase-3
      activity by doses of 100-400 muM of EGCG. This suggests the Cdk2- and caspase-3
      dependent apoptotic effects of EGCG. Moreover, EGCG was more effective than EC,
      ECG, and EGC in changing the apoptotic signals. Results of this study may relate
      to the mechanism by which EGCG modulates body weight.

PMID- 15998136
TI  - Effects of succinylation on the structure and thermostability of lysozyme.
AB  - The influence of succinylation on lysozyme is studied using circular dichroism,
      fluorescence spectroscopy, and differential scanning calorimetry. The
      spectroscopic data reveal that at room temperature the structures of succinylated
      lysozyme and native lysozyme are similar. However, the calorimetric results show
      that the thermal stability of succinylated lysozyme is lower than that of native
      lysozyme. For succinylated lysozyme, the denaturation temperature (Td) varies in
      the range of 325-333 K (52-60 degrees C) and the associated denaturation enthalpy
      (DeltadenH) varies between 225 and 410 kJ/mol. For lysozyme, Td is 342-349 K (69
      76 degrees C) and DeltadenH is 440-500 kJ/mol. From these data, the change in the
      heat capacity (DeltadenCp) upon thermal denaturation is derived. For lysozyme,
      DeltadenCp is 7.5 kJ/mol/K, and for succinylated lysozyme, it is 16.7 kJ/mol/K.
      The value of DeltadenCp for lysozyme is comparable to previously reported values.
      The high value of DeltadenCp for succinylated lysozyme is explained in terms of
      an extended degree of unfolding of the secondary structure and exposure of the
      apolar parts of the succinyl groups. Furthermore, the Gibbs energy of
      denaturation, as a function of temperature, derived from the thermodynamic
      analysis of the calorimetric data, indicates a cold-denaturated state of
      succinylated lysozyme below 20 degrees C. However, because a denatured state at
      low temperatures could not be detected by CD or fluorescence measurements, the
      native state may be considered to be metastable at those conditions.

PMID- 15998137
TI  - The identification of starch phosphorylase in the developing mungbean (Vigna
      radiata L.).
AB  - Starch phosphorylase (SP) in immature mungbean (Vigna radiata L. cv KPS1) seed
      soluble extract was detected by in situ activity staining and identified by MALDI
      TOF mass analysis. After in situ SP assay on native-PAGE, a major starch-enzyme
      complex was located on the gel zymogram in a dose-dependent manner. This complex
      depicted two major SP-activity related proteins, 105 kDa and 55 kDa, by SDS-PAGE.
      The mass and predicted sequence of the tryptic fragments of the isolated 105 kDa
      protein, analyzed by MALDI-TOF spectroscopy and bioinformatic analysis, confirmed
      it to be mungbean SP as a result of high similarity to the L-SP of known plant.
      Polyclonal antibodies raised from the 55 kDa recognized both the 105 kDa and the
      55 kDa proteins on the Western blot and neutralized partial SP activity,
      indicating that the two proteins were immunologically related. The 55 kDa protein
      possess high similarity to the N-terminal half of the 105 kDa SP was further
      confirmed. The SP activity and the activity stained protein density in mungbean
      soluble extract decreased as the seed size increased during early seed growth.
      These data indicate that mungbean 105 kDa SP and SP activity-related 55 kDa were
      identified in the developing mungbean.

PMID- 15998138
TI  - Interactions of alpha-amylase and calcium chelator during neutral detergent fiber
      analysis.
AB  - Amylase and calcium chelators, such as disodium ethylene diaminotetraacetate
      (EDTA), are used in analysis of neutral detergent fiber (NDF) to dissolve starch
      and pectin, respectively. However, these reagents may interfere with each other's
      activity. Six combinations of alpha-amylase and EDTA were examined for
      determining NDF values of beet pulp (Beta vulgaris), ground corn (Zea mays L.),
      timothy hay (Phleum pratense), and soybean meal (Glycine max L). For treatment A,
      2.5 mL of alpha-amylase was added 5 min after boiling. Other treatments differed
      as follows: (B) 4.5 mL of alpha-amylase, (C) 4.5 mL of alpha-amylase added 30 min
      after boiling, (D) delayed addition of EDTA to 30 min after boiling, (E) no EDTA,
      and (F) no alpha-amylase. Inclusion of EDTA interfered with amylase activity in
      corn grain samples, and addition of amylase to beet pulp and soybean meal samples
      reduced the effectiveness of EDTA and increased ash in the NDF residue. Amylase
      should not be used for samples that do not contain starch. Calculating NDF on an
      ash-free basis minimized the negative effects of amylase on EDTA activity.

PMID- 15998139
TI  - High-pressure induced physicochemical and functional modifications of low-density
      lipoproteins from hen egg yolk.
AB  - High-pressure treatment represents a potential method to stabilize
      microbiologically agricultural raw materials that are sensitive to heat
      treatments. Low-density lipoproteins (LDL), the main contributors to the
      exceptional emulsifying properties of yolk, are particularly sensitive to heat
      treatment. In this study, high-pressure treatments have been performed on LDL,
      and their impact on LDL physicochemical and emulsifying properties has been
      assessed. LDL dispersions at two pH levels (pH 3 and 8) were treated at different
      pressure levels: 200, 400, and 600 MPa at 20 degrees C. LDL dispersion
      characteristics (solubility, aggregation, and protein denaturation) and LDL
      emulsifying properties (o/w 30:70 emulsions: droplet size, flocculation, and
      protein adsorption) of nontreated and high-pressure treated dispersions were
      compared. Solubility is not altered by high-pressure treatment whatever the pH,
      whereas aggregation and protein denaturation are drastically enhanced, in
      particular at pH 8. The effects of these modifications on LDL emulsifying
      properties are mainly a diminution of the flocculation (depletion and bridging)
      at this same pH. Finally, it seems that high-pressure treatment combined with an
      alkaline pH decreases droplet flocculation of LDL dispersions.

PMID- 15998140
TI  - Changes in sulfhydryl content of egg white proteins due to heat and pressure
      treatment.
AB  - The sulfhydryl (SH) content of egg white proteins (10% v/v or 9.64 mg of
      protein/mL) after heat (50-85 degrees C) and combined heat- and high-pressure
      treatments (100-700 MPa, 10-60 degrees C) was determined using 5',5-dithiobis (2
      nitrobenzoic acid) (DTNB), both for the soluble fraction and the total protein
      fraction. Only irreversible changes were taken into account. Both physical
      treatments were performed at two pH levels: pH 7.6, corresponding to the pH of
      fresh egg white, and pH 8.8, corresponding to that of aged egg white. Both heat
      and combined heat- and high-pressure treatment resulted in an exposure of buried
      SH groups. These exposed SH groups were involved in the formation of disulfide
      bond stabilized protein aggregates, as shown by gel electrophoresis. Under severe
      processing conditions (above 70 degrees C at atmospheric pressure or above 500
      600 MPa, depending on the temperature applied), a decrease in total SH content
      could be observed, probably due to the formation of disulfide bonds by oxidation,
      especially at alkaline pH when the thiolate anion was more reactive. The high
      degree of exposure of sulfhydryl groups, and subsequent oxidation and sulfhydryl
      disulfide bond exchange reactions resulting in soluble aggregates, can explain
      why pressure-induced egg white gels are softer and more elastic than heat-induced
      ones. When pressure treatment was performed at low temperatures (e.g., 10 degrees
      C), a lower pressure was required to induce similar changes in the sulfhydryl
      content, as compared to higher temperatures (e.g., 25 degrees C), indicating an
      antagonistic effect between pressure and temperature in the domain studied (10-60
      degrees C, 100-700 MPa). Treatment conditions resulting in extensive protein
      insolubilization were accompanied by a transfer of free sulfhydryl groups from
      the soluble to the insoluble protein fraction. These SH groups were mainly
      accessible to DTNB.

PMID- 15998141
TI  - Mechanism of oxymyoglobin oxidation in the presence of oxidizing lipids in bovine
      muscle.
AB  - Lipid oxidation and oxymyoglobin oxidation were measured in bovine muscle
      homogenates. M. longissimus dorsi homogenates (25% w/w, pH 5.7) were prepared,
      held at 4 degrees C, and subjected to one of the following treatments: (i)
      stirred and bubbled with oxygen, (ii) stirred with no oxygen, or (iii) neither
      stirred nor bubbled with oxygen (control). Lipid oxidation was initiated with 45
      microM ferric chloride/sodium ascorbate. Lipid oxidation was highest and
      oxymyoglobin oxidation lowest in the homogenate bubbled with oxygen while lipid
      oxidation was lowest and oxymyoglobin oxidation highest in the control
      homogenate. Dissolved oxygen became depleted over time in the control homogenate,
      remained high in the homogenate bubbled with oxygen, but decreased and then
      increased in the homogenate stirred with no oxygen. Free radical formation was
      lower in the control homogenate than in the stirred homogenates as determined by
      spin trapping and electron spin resonance detection. The data indicated that
      lipid oxidation-induced oxygen depletion, as opposed to primary or secondary
      lipid oxidation products, is a likely cause of oxymyoglobin oxidation in muscle
      systems.

PMID- 15998142
TI  - Structure and stability of the potato cysteine protease inhibitor group (cv.
      Elkana).
AB  - The conformational stability of potato cysteine protease inhibitor (PCPI), the
      second most abundant protease inhibitor group in potato tuber, was investigated
      at ambient temperature and upon heating using far- and near-UV circular dichroism
      spectroscopy, fluorescence spectroscopy, and differential scanning calorimetry
      (DSC). The PCPI isoforms investigated have a highly similar structure at both the
      secondary and the tertiary level. PCPI isoforms show structural properties
      similar to those of the potato serine protease inhibitor group and the Kunitz
      type soybean trypsin inhibitor, a known beta-II protein. Therefore, PCPI isoforms
      are also classified as members of the beta-II protein subclass. Results show that
      the thermal unfolding of PCPI isoforms does not follow a two-state mechanism and
      that at least one intermediate is present. The occurrence of this intermediate is
      most apparent in the thermal unfolding of PCPI 8.3 as indicated by the presence
      of two peaks in the DSC thermogram. Additionally, the formation of aggregates
      (>100 kDa), especially at low scan rates, increases the apparent cooperativity of
      the unfolding.

PMID- 15998143
TI  - Properties and stability of oil-in-water emulsions stabilized by coconut skim
      milk proteins.
AB  - Protein fractions were isolated from coconut: coconut skim milk protein isolate
      (CSPI) and coconut skim milk protein concentrate (CSPC). The ability of these
      proteins to form and stabilize oil-in-water emulsions was compared with that of
      whey protein isolate (WPI). The solubility of the proteins in CSPI, CSPC, and WPI
      was determined in aqueous solutions containing 0, 100, and 200 mM NaCl from pH 3
      to 8. In the absence of salt, the minimum protein solubility occurred between pH
      4 and 5 for CSPI and CSPC and around pH 5 for WPI. In the presence of salt (100
      and 200 mM NaCl), all proteins had a higher solubility than in distilled water.
      Corn oil-in-water emulsions (10 wt %) with relatively small droplet diameters
      (d32 approximately 0.46, 1.0, and 0.5 mum for CSPI, CSPC, and WPI, respectively)
      could be produced using 0.2 wt % protein fraction. Emulsions were prepared with
      different pH values (3-8), salt concentrations (0-500 mM NaCl), and thermal
      treatments (30-90 degrees C for 30 min), and the mean particle diameter, particle
      size distribution, zeta-potential, and creaming stability were measured.
      Considerable droplet flocculation occurred in the emulsions near the isoelectric
      point of the proteins: CSPI, pH approximately 4.0; CSPC, pH approximately 4.5;
      WPI, pH approximately 4.8. Emulsions with monomodal particle size distributions,
      small mean droplet diameters, and good creaming stability could be produced at pH
      7 for CSPI and WPI, whereas CSPC produced bimodal distributions. The CSPI and WPI
      emulsions remained relatively stable to droplet aggregation and creaming at NaCl
      concentrations of < or =50 and < or =100 mM, respectively. In the absence salt,
      the CSPI and WPI emulsions were also stable to thermal treatments at < or =80 and
      < or =90 degrees C for 30 min, respectively. These results suggest that CSPI may
      be suitable for use as an emulsifier in the food industry.

PMID- 15998144
TI  - Characterization and histochemical localization of nonspecific esterase from
      ascocarps of desert truffle (Terfezia claveryi Chatin).
AB  - An esterase activity from Terfezia claveryi Chatin ascocarps, a mycorrhizal
      hypogeous fungus, is described for the first time. The enzyme was partially
      purified using phase partitioning in Triton X-114 (TX-114), achieving a reduction
      of 87% in the triglyceride content and the removal of 63% of phenols. The enzyme
      showed maximum activity toward short-chain p-nitrophenyl esters, and no
      interfacial activation was observed, indicating that the enzyme responsible for
      this activity is an esterase and not a lipase. This esterase presented its
      maximum activity at pH 7.4 and 60 degrees C. The values obtained for Km at pH 7.4
      were 0.3 mM for p-nitrophenyl butyrate and 0.6 mM for p-nitrophenyl acetate with
      catalytic efficiencies (Vmax/Km) of 0.23 and 0.32, respectively. T. claveryi
      esterase was inhibited by phenylboric acid, indicating that serine residues were
      involved in the enzyme activity. This activity was localized only in the
      hypothecium and was absent from the peridium and gleba.

PMID- 15998145
TI  - Nitrogen isotope relationships between crops and fertilizer: implications for
      using nitrogen isotope analysis as an indicator of agricultural regime.
AB  - The effect of fertilizer type, amount of fertilizer applied, growing medium, and
      water type on the nitrogen-15 content of carrots, tomatoes, and lettuces has been
      investigated. Crops grown using synthetic nitrogen fertilizer were isotopically
      lighter than those grown using pelleted chicken manure. For example, for
      equivalent amounts of nitrogen applied, carrots grown with ammonium nitrate
      fertilizer had delta15N values between 3 per thousand and 4 per thousand lower
      than those grown using pelleted chicken manure. Plants grown in peat-based
      compost were generally found to be isotopically lighter than those grown in
      composted bark based compost. Results suggest that nitrate content and the
      delta15N of the nitrate in irrigation water may also influence crop delta15N.
      Wider implications of using crop delta15N more generally as an indicator of
      whether synthetic nitrogen fertilizers have been applied to a crop and the
      possible application and limitations of using crop delta15N as an indicator of
      agricultural regime (organic/conventional) are discussed.

PMID- 15998146
TI  - Relationships between oxidative stability, triacylglycerol composition, and
      antioxidant content in olive oil matrices.
AB  - In olive oils, relationships between oxidative stability, glyceridic composition,
      and antioxidant content were investigated. Lipid matrices, obtained by
      purification of olive and high-oleic sunflower oils, were spiked with
      hydroxytyrosol, alpha-tocopherol, and mixtures of them and then subjected to
      oxidation in a Rancimat apparatus at 100 degrees C. At the same concentration of
      antioxidants, induction time (IT) decreased as the unsaturation rate of the
      matrix increased, but only fair correlations were found with fatty acid
      composition. Oxidative susceptibility (OS(TAG)) was calculated as a function of
      the relative oxidation rate of the triacylglycerols, and a linear relationship-IT
      (h) = (a + b)OS(TAG)-between induction time and this parameter showed a good
      correlation coefficient (r > 0.990, p < 0.001). In the case of matrices with a
      single antioxidant, origin ordinate (a) and slope (b) can be calculated as a
      function of the antioxidant concentration. In matrices spiked with mixtures of
      hydroxytyrosol and alpha-tocopherol, a simple relationship between the
      coefficients a and b and the concentration of antioxidants cannot be established
      because additive and subtractive effects occur depending on the relative
      concentrations of both antioxidants. However, approximate values for these
      coefficients can be obtained, allowing the estimation of the oil stability. In
      various olive oils, an acceptable agreement was found between the IT
      experimentally determined and that calculated from the oil composition. These
      results confirmed that the Rancimat stability of olive oils mainly depends on
      triacylglycerol composition and concentrations of o-diphenols and alpha
      tocopherol.

PMID- 15998147
TI  - Gingerol content of diploid and tetraploid clones of ginger (Zingiber officinale
      Roscoe).
AB  - Ginger (Zingiber officinale Roscoe), a monocotyledonous, sterile cultigen, is
      widely used as a spice, flavoring agent, and herbal medicine. The pungency of
      fresh ginger is due to a series of homologous phenolic ketones of which [6]
      gingerol is the major one. The gingerols are thermally unstable and can be
      converted to their corresponding shogaols, which are present in dried ginger.
      Fresh rhizomes of 17 clones of Australian ginger, including commercial cultivars
      and experimental tetraploid clones, were assayed by HPLC for gingerols and
      shogaols. [6]-Gingerol was identified as the major pungent phenolic compound in
      all samples, while [8]- and [10]-gingerol occurred in lower concentrations. One
      cultivar known as "Jamaican" contained the highest concentrations of all three
      gingerols and was the most pungent of the clones analyzed. Gingerols were stable
      in ethanolic solution over a 5-month period when stored at 4 degrees C. Shogaols
      were not identified in the extracts prepared from fresh rhizomes at ambient
      temperature, confirming that these compounds are not native constituents of fresh
      ginger. In contrast to previous findings, this study did not find significant
      differences in gingerol concentrations between the tetraploid clones and their
      parent diploid cultivar.

PMID- 15998148
TI  - Lipase-catalyzed acidolysis of tripalmitin with hazelnut oil fatty acids and
      stearic acid to produce human milk fat substitutes.
AB  - Structured lipids (SLs) containing palmitic, oleic, stearic, and linoleic acids,
      resembling human milk fat (HMF), were synthesized by enzymatic acidolysis
      reactions between tripalmitin, hazelnut oil fatty acids, and stearic acid.
      Commercially immobilized sn-1,3-specific lipase, Lipozyme RM IM, obtained from
      Rhizomucor miehei was used as the biocatalyst for the enzymatic acidolysis
      reactions. The effects of substrate molar ratio, reaction temperature, and
      reaction time on the incorporation of stearic and oleic acids were investigated.
      The acidolysis reactions were performed by incubating 1:1.5:0.5, 1:3:0.75, 1:6:1,
      1:9:1.25, and 1:12:1.5 substrate molar ratios of tripalmitin/hazelnut oil fatty
      acids/stearic acid in 3 mL of n-hexane at 55, 60, and 65 degrees C using 10%
      (total weight of substrates) of Lipozyme RM IM for 3, 6, 12, and 24 h. The fatty
      acid composition of reaction products was analyzed by gas-liquid chromatography
      (GLC). The fatty acids at the sn-2 position were identified after pancreatic
      lipase hydrolysis and GLC analysis. The results showed that the highest C18:1
      incorporation (47.1%) and highest C18:1/C16:0 ratio were obtained at 65 degrees C
      and 24 h of incubation with the highest substrate molar ratio of 1:12:1.5. The
      highest incorporation of stearic acid was achieved at a 1:3:0.75 substrate molar
      ratio at 60 degrees C and 24 h. For both oleic and stearic acids, the
      incorporation level increased with reaction time. The SLs produced in this study
      have potential use in infant formulas.

PMID- 15998149
TI  - Soybean peroxidase-catalyzed oxidation of luminol by hydrogen peroxide.
AB  - Anionic soybean peroxidase Glycine max (SbP) is shown to efficiently catalyze
      luminol oxidation by hydrogen peroxide. Contrary to horseradish peroxidase, the
      presence of p-iodophenol in the reaction medium affects slightly the efficiency
      of SbP catalysis. A maximal intensity of chemiluminescence, produced through this
      enzymatic reaction, was detected at pH 8.4-8.6. Contrary to anionic palm tree
      peroxidase, in the presence of SbP, chemiluminescence intensity increases with
      the reaction buffer concentration. The detection limit of SbP in the reaction of
      luminol oxidation is 0.3 x 10(-12) M. Therefore, high sensitivity in combination
      with the long-term chemiluminescent signal is indicative of good prospects for
      application of this enzyme in enzyme immunoassay with chemiluminescent detection.

PMID- 15998150
TI  - Model studies on the influence of high hydrostatic pressure on the formation of
      glycated arginine modifications at elevated temperatures.
AB  - Aqueous solutions of Nalpha-acetylarginine and glucose were reacted for 2 h with
      pressure application from 0 to 600 MPa and varying temperatures between 90 and
      120 degrees C. After enzymatic deacetylation of the reaction products, the
      glycated amino acids were separated by means of a self-assembled preparative ion
      exchange chromatography system using ninhydrin detection. On the basis of the use
      of eight synthesized reference compounds known in the literature as
      posttranslational arginine modifications, first, the presence of several glycated
      amino acids could be excluded. On the other hand, N5-[[(1
      carboxyethyl)amino]iminomethyl]ornithine [N7-(1-carboxyethyl)arginine; N7-CEA;
      12] was identified as a previously unknown arginine modification based on LC-MS,
      NMR measurements, and synthesis. In addition, N5-(5-hydro-5-methyl-4-imidazolon-2
      yl)-L-ornithine (1) was identified as a further major reaction product. In
      further experiments, the formation of 1 and 12 was quantitatively followed at
      different pressures and/or temperatures. The results indicated that high
      hydrostatic pressure at elevated temperatures significantly increased the amounts
      of both arginine modifications. 2-Oxopropanal, known to form 1 in a reaction with
      arginine, was also quantified to explain the different yields observed after
      pressure application. A new formation mechanism leading to 12 by a reaction of
      the guanidine group or arginine with 2-oxopropanal is discussed.

PMID- 15998151
TI  - Influence of vine vigor on grape (Vitis vinifera L. Cv. Pinot Noir) and wine
      proanthocyanidins.
AB  - The relationships between variations in grapevine (Vitis vinifera L. cv. Pinot
      noir) growth and resulting fruit and wine phenolic composition were investigated.
      The study was conducted in a commercial vineyard consisting of the same clone,
      rootstock, age, and vineyard management practices. The experimental design
      involved monitoring soil, vine growth, yield components, and fruit composition
      (soluble solids, flavan-3-ol monomers, proanthocyanidins, and pigmented polymers)
      on a georeferenced grid pattern to assess patterns in growth and development.
      Vine vigor parameters (trunk cross-sectional area, average shoot length, and leaf
      chlorophyll) were used to delineate zones within both blocks to produce research
      wines to investigate the vine-fruit-wine continuum. There was no significant
      influence of vine vigor on the amount of proanthocyanidin per seed and only
      minimal differences in seed proanthocyanidin composition. However, significant
      increases were found in skin proanthocyanidin (mg/berry), proportion of (-)
      epigallocatechin, average molecular mass of proanthocyanidins, and pigmented
      polymer content in fruit from zones with a reduction in vine vigor. In the wines
      produced from low-vigor zones, there was a large increase in the proportion of
      skin tannin extracted into the wine, whereas little change occurred in seed
      proanthocyanidin extraction. The level of pigmented polymers and proanthocyanidin
      molecular mass were higher in wines made from low-vigor fruit compared to wines
      made from high-vigor fruit, whereas the flavan-3-ol monomer concentration was
      lower.

PMID- 15998152
TI  - Compositional variations for alpha-galactosides in different species of
      leguminosae, brassicaceae, and barley: a chemotaxonomic study based on
      chemometrics and high-performance capillary electrophoresis.
AB  - The contents of raffinose family oligosaccharides (RFO) and sucrose in Brassica,
      Lupinus, Pisum, and Hordeum species were investigated by chemometric principal
      component analysis (PCA). Hordeum samples contained sucrose and raffinose, and
      Brassica samples all contained sucrose, raffinose, and stachyose. In addition to
      these, the Pisum samples contained verbascose and the Lupinus samples also
      contained ajugose. High stachyose and low ajugose contents were found in Lupinus
      albus in contrast to Lupinus angustifolius, having low stachyose and high ajugose
      contents. Lupinus luteus had average stachyose and ajugose contents, whereas
      large amounts of verbascose were accumulated in these seeds. Lupinus mutabilis
      had high stachyose and low ajugose contents, similar to the composition in L.
      albus but showing higher raffinose content. The Brassica samples also showed
      compositional RFO variations within the species, and subgroup formations were
      discovered within the investigated Brassica napus varieties. PCA results
      indicated compositional variations between the investigated genera and within the
      various species of value as chemotaxonomic defined parameters and as tools in
      evaluations of authenticity/falsifications when RFO-containing plants are used
      as, for example, feed and food additives.

PMID- 15998153
TI  - Impact of Fusarium culmorum on the polysaccharides of wheat flour.
AB  - To assess the effects of Fusarium infection on the polysaccharides of winter
      wheat grain (Triticum aestivum L.), grain samples obtained from plants
      artificially inoculated with Fusarium culmorum were analyzed. Microscopy revealed
      obvious damage to the starch granules in the seriously infected samples. The
      Fusarium infection had no analytically detectable influence on the starch and
      total insoluble dietary fiber content of the wheat grain. There were
      significantly positive relationships between alpha-amylase activity, cellulase
      activity, total soluble dietary fiber content, pentosan content, and degree of
      infection quantified by an enzyme-linked immunosorbant assay, which would
      indicate the importance of fungal enzymes. A distinct higher Hagberg falling
      number (FN) was determined in the seriously infected samples, while the viscosity
      and sucrose content of the flour decreased. However, the addition of a liquid
      medium contaminated with F. culmorum led to a significant decrease in the FN.
      Depending on the type of buffer used, the alpha-amylase of F. culmorum
      demonstrated its maximum activity between pH 5.5 and pH 7.0 at 30-50 degrees C.
      Remarkably, this fungal alpha-amylase showed a thermostable characteristic and
      was active over a wide range of temperatures, from 10 to 100 degrees C. This type
      of thermostability suggests that the alpha-amylase of F. culmorum may damage
      starch granules throughout the processing of wheat flour, thereby inducing weak
      dough properties and unsatisfactory bread quality.

PMID- 15998154
TI  - Mycoflora and occurrence of alternariol and alternariol monomethyl ether in
      Brazilian sunflower from sowing to harvest.
AB  - The present study aimed to analyze the mycoflora and the occurrence of
      alternariol (AOH) and alternariol monomethyl ether (AME) in grain samples of
      sunflower during different stages of plant development in Nova Odessa, State of
      Sao Paulo, Brazil. The data obtained were correlated with the presence of fungi
      in soil, wind-dispersed fungi, and the predominant climatic conditions of the
      region where the experiment was carried out. Analysis of the mycoflora revealed
      the presence of Fusarium verticillioides and Alternaria alternata in 70% and 46%
      of the samples, respectively. The profile of wind-dispersed fungi also showed F.
      verticillioides as the most frequently isolated fungus (68%), although A.
      alternata was detected in 28% of samples. In soil, Penicillium was the most
      frequent species (49.9%), followed by F. verticillioides (47.7%) and A. alternata
      (10.9%). Regarding water activity, sunflower grains presenting a high frequency
      of isolation of F. verticillioides and A. alternatahad a water activity ranging
      from 0.92 to 0.96, and statistical analysis revealed a negative linear
      correlation between the isolation of fungi and water activity. HPLC analysis
      showed that 18% of the sunflower grains were contaminated with alternariol (24.9
      170.9 ng/g) and 10% with alternariol monomethyl ether (14.1-108.6 ng/g). The
      contamination of sunflower grains with AOH and AME in the field was low when
      compared to the LD50 necessary to cause toxicity to animals. However, the
      contamination with other toxigenic fungi such as F. verticillioides may indicate
      the presence of other mycotoxins in sunflower grains and a possible synergistic
      effect between them. This is the first report of the natural occurrence of
      alternariol and alternariol monomethyl ether in sunflower grains in Brazil.

PMID- 15998155
TI  - Comment on cluster analysis applied to the exploratory analysis of commercial
      spanish olive oils by means of excitation-emission fluorescence spectroscopy.

PMID- 15998163
TI  - Cost-effectiveness of sibutramine in the LOSE Weight Study: evaluating the role
      of pharmacologic weight-loss therapy within a weight management program.
AB  - the cost-effectiveness of drug therapy when used in conjunction with a weight
      management program (WMP) for treatment of obesity. The objective was to compare
      the cost-effectiveness of sibutramine (Meridia) plus a structured WMP versus only
      a structured WMP in both overweight and obese individuals. The core WMP was a
      physician-supervised, multidisciplinary program for which each enrollee paid $100
      out of pocket. METHODS: A cost-effectiveness analysis was performed based upon
      the results of a previously published randomized controlled trial conducted
      within a managed care organization. The target population for this study was
      obese or overweight persons. The perspective of the study was that of a managed
      care organization. The intervention consisted of subjects receiving a WMP with or
      without sibutramine. The primary outcomes of this study were (a) absolute change
      in body weight and percentage change in body weight over 12 months, (b) change in
      obesity-related and total medical costs from 12 months prior to enrollment
      through 12 months after enrollment, and (c) cost-effectiveness in terms of cost
      per pound of weight loss. All costs were adjusted to 2004 dollars using the
      respective components of the consumer price index for each medical service or
      medication. RESULTS: A total of 501 evaluable subjects were enrolled in the
      study, with 281 receiving sibutramine plus a structured WMP and 220 receiving
      only the structured WMP. The meanSD weight loss was significantly greater in the
      sibutramine (13.715.5 pounds, 4.8%) group than in the nondrug group (513.2
      pounds, 2.2%) (P < 0.001). The change in obesity-related total cost was a median
      increase of $408 for the sibutramine group compared with $31 for the nondrug
      group (P < 0.001). The change in total health care cost was a median $1,279
      increase in the sibutramine group compared with $271 for the nondrug group (P <
      0.001). Adding sibutramine to the WMP increased the total cost by $44 per
      additional pound of weight loss (95% confidence interval, 42-46). Sensitivity
      analyses found that the results were sensitive to the price of sibutramine,
      whereas varying the cost of clinic visits did not substantially change the
      results. CONCLUSION: Patients enrolled in a WMP receiving sibutramine had greater
      weight loss and decrease in body mass index at greater cost than did patients
      enrolled in the same program who did not receive sibutramine. There were no
      observed savings in total health care resource utilization or cost in the
      sibutramine group compared with the nondrug group.

PMID- 15998164
TI  - Direct costs of opioid abuse in an insured population in the United States.
AB  - OBJECTIVE: To (a) describe the demographics of opioid abusers; (b) compare the
      prevalence rates of selected comorbidities and the medical and drug utilization
      patterns of opioid abusers with patients from a control group, for the period
      from 1998 to 2002; and (c) calculate the mean annual per-patient total health
      care costs (e.g., inpatient, outpatient, emergency room, drug, other) from the
      perspective of a private payer. METHODS: An administrative database of medical
      and pharmacy claims from 1998 to 2002 of 16 self-insured employer health plans
      with approximately 2 million lives was used to identify "opioid abusers"-
      patients with claims associated with ICD-9-CM (International Classification of
      Diseases, 9th Revision, Clinical Modification) codes for opioid abuse (304.0,
      304.7, 305.5, and 965.0 [excluding 965.01]). A control group of nonabusers was
      selected using a matched sample (by age, gender, employment status, and census
      region) in a 3:1 ratio. Per-patient annual health care costs (mean total medical
      and drug costs) were measured in 2003 U.S. dollars. Multivariate regression
      techniques were also used to control for comorbidities and to compare costs with
      a benchmark of depressed patients. RESULTS: 740 patients were identified as
      opioid abusers, a prevalence of 8 in 10,000 persons aged 12 to 64 years
      continuously enrolled in health care plans for whom 12 months of data were
      available for calculating costs. Opioid abusers, compared with nonabusers, had
      significantly higher prevalence rates for a number of specific comorbidities,
      including nonopioid poisoning, hepatitis (A, B, or C), psychiatric illnesses, and
      pancreatitis, which were approximately 78, 36, 9, and 21 (P<0.01) times higher,
      respectively, compared with nonabusers. Opioid abusers also had higher levels of
      medical and prescription drug utilization. Almost 60% of opioid abusers had
      prescription drug claims for opioids compared with approximately 20% for
      nonabusers. Prevalence rates for hospital inpatient visits for opioid abusers
      were more than 12 times higher compared with nonabusers (P<0.01). Mean annual
      direct health care costs for opioid abusers were more than 8 times higher than
      for nonabusers ($15,884 versus $1,830, respectively, P < 0.01). Hospital
      inpatient and physician-outpatient costs accounted for 46% ($7,239) and 31%
      ($5,000) of opioid abusers. health care costs, compared with 17% ($310) and 50%
      ($906), respectively, for nonabusers. Mean drug costs for opioid abusers were
      more than 5 times higher than costs for nonabusers ($2,034 vs. $386,
      respectively, P<0.01), driven by higher drug utilization (including opioids) for
      opioid abusers. Even when controlling for comorbidities using a multivariate
      regression model of a matched control of depressed patients, the average health
      care costs of opioid abusers were 1.8 times higher than the average health care
      costs of depressed patients. CONCLUSION: The high costs of opioid abuse were
      driven primarily by high prevalence rates of costly comorbidites and high
      utilization rates of medical services and prescription drugs.

PMID- 15998165
TI  - Consumer understanding and satisfaction associated with a 3-tier prescription
      drug benefit.
AB  - OBJECTIVE: The purpose of this research was to investigate consumer understanding
      and satisfaction associated with a 3-tier prescription drug benefit among users
      of the prescription drug benefit. METHODS: This study involved a self
      administered postal questionnaire and the use of prescription drug claims to
      evaluate utilization of prescription medications. Fifteen hundred subjects were
      randomly selected based on the following inclusion criteria. Each subject had to
      (1) be enrolled in a 3-tier copayment ($10 generic, $20 formulary brand, $35
      nonformulary brand) prescription drug benefit; (2) be the primary beneficiary
      (cardholder); (3) be >18 years of age; (4) have received at least 1 prescription
      medication using his or her prescription drug insurance; and (5) have a mailing
      address on file. RESULTS: A total of 479 usable responses were returned (35%
      response rate). The mean (SD) understanding score was 2.22 (1.54) (range: 0 to
      6). Fewer than 1% of respondents correctly answered all 6 items used to measure
      the level of understanding. The mean (SD) satisfaction score was 54.32 (19.69)
      (range: 0 to 100). Experience with purchasing a medication within a particular
      copayment tier was predictive of correctly answering the item related to that
      tier.s copayment amount. Multiple regression analysis revealed a relationship
      between the amount of use of the drug benefit and the degree of satisfaction with
      the drug benefit. There was no significant relationship between the level of
      understanding and the degree of satisfaction with prescription drug insurance.
      CONCLUSION: The average level of beneficiary understanding of the 3-tier
      copayment prescription drug benefit was very low, and the average degree of
      respondent satisfaction appeared to be near neutral. There was no significant
      relationship between the level of understanding and the degree of satisfaction
      with prescription drug benefits. The level of understanding was proportional to
      the amount of drug benefit use, but the degree of satisfaction was not related to
      the amount of drug benefit use.

PMID- 15998166
TI  - Effect of patient notification of formulary change on formulary adherence.
AB  - OBJECTIVE: To evaluate the impact of patient notification of impending formulary
      changes on formulary adherence. METHODS: This pilot program in a large, Midwest
      based health insurer utilized a randomized controlled trial research design. A
      list of 30 chronic-use medications that were to change formulary status were
      selected for the pilot. A review of adjudicated pharmacy claims records was
      performed to identify patients receiving one or more of the formulary change
      medications on the list. Members of 112 individual health plans of this large
      health insurer, all of whom were subject to the same drug formulary, were
      randomized to either the intervention (letter) or control arm. Patients in the
      intervention arm were sent a targeted communication that described the patient.s
      formulary change medication(s) and provided therapeutic option(s) for the
      formulary change medication(s). Pharmacy claims for patients in both arms were
      examined at 110 days after the date of the mailing to determine if there was a
      switch to a formulary alternative. Multivariate regression modeling was performed
      to adjust for baseline differences between the arms. RESULTS: A total of 7,247
      unique formulary change medication regimens were identified (3,817 in the control
      arm and 3,430 in the letter arm) for 6,518 subjects (3,387 in the control arm and
      3,131 in the letter arm). A higher proportion of formulary change medication
      regimens in the intervention arm were switched to a formulary alternative
      compared with the control arm (19.2% vs. 12.0%, P<0.001). After adjustment for
      baseline differences, regression modeling indicated that subjects in the
      intervention arm were 1.33 times more likely to switch to a formulary alternative
      (P<0.001). CONCLUSION: A letter-based, formulary change notification program is a
      pragmatic and effective strategy to increase drug formulary adherence. Such a
      program does not restrict access to medications but, rather, provides education
      and personalized information that may allow patients to participate more actively
      in their pharmacotherapy decision making.

PMID- 15998167
TI  - Similar medication compliance and control of dyslipidemia with simvastatin or
      atorvastatin in a staff-model HMO medical clinic.
AB  - OBJECTIVE: The primary objective of this study was to determine medication
      compliance rates and dyslipidemia control in a patient population receiving
      simvastatin or atorvastatin (statins) in a unique staff-model health maintenance
      organization (HMO). The secondary objective of this study was to measure the
      effect of gender and statin regimen on the success rate of dylipidemia control
      and medication compliance. METHODS: This was a retrospective chart review
      conducted for patients with a diagnosis of dyslipidemia who received monotherapy
      with a statin for cholesterol reduction. Patients received care at an outpatient
      clinic during a 12-month study period (December 1998 through December 1999).
      Patients were excluded if they did not have a low-density lipoprotein cholesterol
      (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentration obtained
      in 1999, did not have a statin prescription filled at least twice the during
      study period, discontinued statin therapy, or received a statin other than
      simvastatin or atorvastatin. Patient medication compliance was assessed using the
      medication possession ratio (MPR). Dyslipidemia control rates were determined
      according to the National Cholesterol Education Program (NCEP) Adult Treatment
      Panel (ATP) II guidelines. RESULTS: A total of 819 patients met inclusion
      criteria for study enrollment (55% male, 45% female). The mean age of the
      patients was 68.5 years. The mean MPR for the entire study group was 0.960.23.
      Men and women had similar mean MPR values (0.970.23 vs. 0.960.22, respectively;
      P=0.76). A nearly identical proportion of patients who received either
      atorvastatin or simvastatin achieved their LDL-C goal, 70.0% vs. 69.6%,
      respectively. Gender was not related to success rate, with 73.0% of women and
      66.9% of men achieving their NCEPdirected LDL-C goal (P=0.06). The rate of
      attainment of ATP II LDL goal was 43.2% (92 of 213) for patients with goal < 100
      mg/dL, 69.1% (226 of 327) for < 130, and 90.7% (252 of 279) for patients with
      goal < 160 mg/dL. CONCLUSIONS: Patients enrolled in a unique staff-model HMO who
      received either simvastatin or atorvastatin exhibited high medication compliance
      and dyslipidemia control rates. Gender did not affect medication compliance or
      attainment of LDL-C goal, and the success of achieving dyslipidemia control was
      not different between atorvastatin and simvastatin.

PMID- 15998168
TI  - Prevalence and types of disease management programs in community pharmacies in
      California.
AB  - OBJECTIVES: To (1) evaluate the prevalence and types of disease management (DM)
      programs provided by independent and chain community pharmacies in the state of
      California, (2) examine the interest among community pharmacists in establishing
      programs, and (3) assess perceived barriers to developing a successful DM program
      in community pharmacy. METHOD: An exploratory telephone survey was conducted from
      February 2003 to February 2004 to collect data from community (primarily
      independent and chainstore) pharmacies across California. The survey evaluated
      existence (or lack of) and types of DM programs in community pharmacies in
      California. Pharmacies that did not have a DM program were queried on their
      interest and decisionmaking authority in establishing new programs. Pharmacies
      that had existing DM programs were sent a follow-up survey to determine the
      details of the DM programs, including challenges in establishing DM programs,
      reimbursement issues, and program effectiveness. RESULTS: The sample comprised
      1,875 pharmacies, 60 (3.2%) of which had existing DM programs. There were
      significantly more independent pharmacies (37) with DM programs than chain-store
      pharmacies (23), P<0.001. There was a statistically significant difference
      between independent and chain pharmacies in operating hours, number of pharmacist
      and nonpharmacist staff members per day, and proximity to a clinic or hospital
      (P<0.05). The most common type of DM program was diabetes, and the second most
      common type was asthma. Limited time, limited staff, and limited reimbursement
      were the 3 most commonly reported barriers to establishing new DM programs. About
      20% of the sample that did not have a DM program reported interest in developing
      DM programs, and an equal percentage reported having the decision-making
      authority to start a program. There were no differences between independent and
      chain pharmacies on interest (P = 0.234); however, there were significantly more
      chain pharmacists that did not have the decision-making authority. Of the 18 of
      60 pharmacies (30%) that had DM programs and responded to the follow-up survey, 9
      respondents (50%) reported monitoring medications as part of their DM program.
      Fifteen of 18 (83%) perceived lack of reimbursement as a challenge to
      implementing DM programs. Only 2 pharmacies reported an increase in revenue as a
      gain from the program, and 2 reported cost savings. Improved patient satisfaction
      was reported by 16 of 18 respondents (89%) with DM programs, but only 8 (44%)
      reported that patient satisfaction was being measured. CONCLUSION: The study
      found that the prevalence of DM programs was very low among California community
      pharmacies and the interest in developing these programs moderate, attributable
      to several barriers such as lack of time, lack of reimbursement, and lack of
      trained personnel. Some of these barriers could be addressed to encourage the
      development and proliferation of DM programs that would improve patient outcomes
      and expand practice roles of pharmacists.

PMID- 15998169
TI  - Which is more elusive, the pot of gold at the end of a rainbow or determining the
      most cost-effective triptan?

PMID- 15998170
TI  - "U can't touch this" with pharmacotherapy alone for weight loss or smoking
      cessation.

PMID- 15998156
TI  - Second-generation (atypical) antipsychotics and metabolic effects: a
      comprehensive literature review.
AB  - Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia
      and lipid dysregulation in patients treated with second-generation (or atypical)
      antipsychotics have raised concerns about a possible association between these
      metabolic effects and treatment with these medications. This comprehensive
      literature review considers the evidence for and against an association between
      glucose or lipid dysregulation and eight separate second-generation
      antipsychotics currently available in the US and/or Europe, specifically
      clozapine, olanzapine, risperidone, quetiapine, zotepine, amisulpride,
      ziprasidone and aripiprazole. This review also includes an assessment of the
      potential contributory role of treatment-induced weight gain in conferring risk
      for hyperglycaemia and dyslipidaemia during treatment with different
      antipsychotic medications. Substantial evidence from a variety of human
      populations, including some recent confirmatory evidence in treated psychiatric
      patients, indicates that increased adiposity is associated with a variety of
      adverse physiological effects, including decreases in insulin sensitivity and
      changes in plasma glucose and lipid levels. Comparison of mean weight changes and
      relative percentages of patients experiencing specific levels of weight increase
      from controlled, randomised clinical trials indicates that weight gain liability
      varies significantly across the different second generation antipsychotic agents.
      Clozapine and olanzapine treatment are associated with the greatest risk of
      clinically significant weight gain, with other agents producing relatively lower
      levels of risk. Risperidone, quetiapine, amisulpride and zotepine generally show
      low to moderate levels of mean weight gain and a modest risk of clinically
      significant increases in weight. Ziprasidone and aripiprazole treatment are
      generally associated with minimal mean weight gain and the lowest risk of more
      significant increases. Published studies including uncontrolled observations,
      large retrospective database analyses and controlled experimental studies,
      including randomised clinical trials, indicate that the different second
      generation antipsychotics are associated with differing effects on glucose and
      lipid metabolism. These studies offer generally consistent evidence that
      clozapine and olanzapine treatment are associated with an increased risk of
      diabetes mellitus and dyslipidaemia. Inconsistent results, and a generally
      smaller effect in studies where an effect is reported, suggest limited if any
      increased risk for treatment-induced diabetes mellitus and dyslipidaemia during
      risperidone treatment, despite a comparable volume of published data. A similarly
      smaller and inconsistent signal suggests limited if any increased risk of
      diabetes or dyslipidaemia during quetiapine treatment, but this is based on less
      published data than is available for risperidone. The absence of retrospective
      database studies, and little or no relevant published data from clinical trials,
      makes it difficult to draw conclusions concerning risk for zotepine or
      amisulpride, although amisulpride appears to have less risk of treatment-emergent
      dyslipidaemia in comparison to olanzapine. With increasing data from clinical
      trials but little or no currently published data from large retrospective
      database analyses, there is no evidence at this time to suggest that ziprasidone
      and aripiprazole treatment are associated with an increase in risk for diabetes,
      dyslipidaemia or other adverse effects on glucose or lipid metabolism. In
      general, the rank order of risk observed for the second-generation antipsychotic
      medications suggests that the differing weight gain liability of atypical agents
      contributes to the differing relative risk of insulin resistance, dyslipidaemia
      and hyperglycaemia. This would be consistent with effects observed in
      nonpsychiatric samples, where risk for adverse metabolic changes tends to
      increase with increasing adiposity. From this perspective, a possible increase in
      risk would be predicted to occur in association with any treatment that produces
      increases in weight and adiposity. However, case reports tentatively suggest that
      substantial weight gain or obesity may not be a factor in up to one-quarter of
      cases of new-onset diabetes that occur during treatment. Pending further testing
      from preclinical and clinical studies, limited controlled studies support the
      hypothesis that clozapine and olanzapine may have a direct effect on glucose
      regulation independent of adiposity. The results of studies in this area are
      relevant to primary and secondary prevention efforts that aim to address the
      multiple factors that contribute to increased prevalence of type 2 diabetes
      mellitus and cardiovascular disease in populations that are often treated with
      second-generation antipsychotic medications.

PMID- 15998171
TI  - COPD: clinical significance of early diagnosis.
AB  - OBJECTIVE: To explain the differential diagnosis of chronic obstructive pulmonary
      disease (COPD) and how COPD can be distinguished in patients who present with
      complaints of dyspnea, (shortness of breath on exertion), with the goal of
      improving earlier diagnosis. SUMMARY: It is important to differentiate COPD from
      other diagnoses when adult patients present with dyspnea. There are several key
      diagnostic indicators for COPD, including, most notably, a history of smoking and
      objective lung-function measurements. COPD remains an underdiagnosed disease,
      chiefly in its milder and more treatable form. The Global Initiative for Chronic
      Obstructive Lung Disease (GOLD)- defined standards for COPD management consist of
      4 components: (1) assess and monitor disease, (2) reduce risk factors, (3) manage
      stable COPD through education and nonpharmacologic and pharmacologic means, and
      (4) manage exacerbations. CONCLUSION: Updated standards for diagnosis and
      treatment-targeted pharmacologic agents have provided physicians and health care
      workers with more specific and targeted treatment modalities for early detection
      and treatment of this progressive disease. Early detection and more accurate
      diagnosis are key in improving outcomes and altering the progression of the
      disease.

PMID- 15998172
TI  - New treatment options in COPD.
AB  - OBJECTIVE: To review the role of long-acting bronchodilators in the treatment of
      chronic obstructive pulmonary disease (COPD), including the importance of
      treatment adherence. SUMMARY: Overall, clinical trials show that compared with
      placebo and ipratropium, tiotropium significantly improves spirometric measures,
      increases quality-of-life scores, and is associated with fewer exacerbations. In
      addition, compared with salmeterol, tiotropium is associated with greater
      improvements in spirometric measures and clinically meaningful increases in
      quality-of-life measures. In comparison with either fluticasone or salmeterol
      alone, the fluticasone/salmeterol combination is associated with statistically
      greater improvement in spirometric and dyspnea measures; however, the combination
      is not associated with fewer exacerbations than either fluticasone or salmeterol
      used by itself. CONCLUSIONS: The 2003 update to the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) guidelines recommends regular treatment with long
      acting bronchodilators for maintenance COPD therapy because of superior
      effectiveness and convenience compared with short-acting bronchodilators. The
      results from trials presented in this article demonstrate that inhaled tiotropium
      is effective in treating COPD and might be considered as a first-line agent for
      maintenance therapy in view of its outcomes data. The convenience of once-daily
      administration would probably contribute to patient adherence and thus to the
      overall efficacy of this agent.

PMID- 15998173
TI  - Analysis of the current care model of the COPD patient: a health outcomes
      assessment and economic evaluation.
AB  - OBJECTIVE: Because chronic obstructive pulmonary disease (COPD) is a common but
      serious illness affecting millions worldwide, we present an overview of the
      disease and discuss its underdiagnosis and treatment options. SUMMARY: COPD, a
      disease encompassing emphysema and chronic bronchitis, is associated with
      cigarette smoking, chronic exposure to environmental pollutants, and,
      occasionally, genetic conditions. The disease is severely underdiagnosed and
      underrecognized. The economic costs of COPD, which accounted for about 14 million
      office visits and 3.5 million hospital days in 1993, are estimated at more than
      $7 billion, and another $8 billion worth of productivity was lost to morbidity
      and mortality in the same year.1 The death rate from COPD is rising, principally
      among women. Uniform diagnosis and treatment standards are now being realized.
      The American Thoracic Society and European Respiratory Society recommend
      treatment, based on worsening symptoms, with bronchodilators and, in more
      advanced cases, inhaled corticosteroids. The Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) treatment algorithm also uses a step-care
      approach. The GOLD guidelines recommend a management program that prevents
      disease progression, relieves symptoms, improves exercise tolerance and health
      status, and prevents and treats complications and exacerbations, thereby reducing
      mortality. The GOLD guidelines recommend avoiding risk factors, using short- or
      long-acting bronchodilators, and adding rehabilitation and inhaled
      glucocorticoids. In severe cases, the GOLD guidelines recommend long-term oxygen
      administration and even surgery. Decisions in managing COPD require a
      consideration of multiple outcomes measures. Although spirometry remains the
      foundation for diagnosis and demonstration of efficacy, the patients and their
      families may be more concerned with symptoms, quality of life, and prevention of
      exacerbations. In patients with COPD, bronchodilators such as tiotropium produce
      significant improvements in all of these outcomes measures. CONCLUSIONS: COPD is
      a common disease that substantially affects patients, health care systems, and
      society. With increasing awareness of the disease, improved diagnostic
      guidelines, and newer cost-effective pharmacologic regimens, this chronic
      progressive disorder can be effectively recognized and treated, helping to
      improve patients. overall health and quality of life.

PMID- 15998174
TI  - Structural equation models for interchangeable dyads: being the same makes a
      difference.
AB  - Structural equation modeling (SEM) offers a flexible method for studying the
      patterns of interdependence in partners' behavior, which lie at the heart of
      interactions and relationships. Although SEM has been applied to the study of
      distinguishable dyads, in which partners are distinguishable by type, such as
      male and female, it has rarely been applied to the study of interchangeable
      dyads, such as male-male or female-female pairs. The authors integrate a wide
      range of dyadic interdependence models--including actor-partner interdependence
      models, mutual-influence models, and common-fate or dyadic personality models-
      into an SEM framework for use with interchangeable dyads. The authors also
      address the use of latent variables at both the dyadic and individual levels,
      whereby substantive relationships in these models can be corrected for errors of
      measurement. Furthermore, the authors discuss the conceptual underpinnings of
      dyadic models and give examples of their application.

PMID- 15998175
TI  - Multilevel modeling of two cyclical processes: extending differential structural
      equation modeling to nonlinear coupled systems.
AB  - The authors present a dynamical multilevel model that captures changes over time
      in the bidirectional, potentially asymmetric influence of 2 cyclical processes.
      S. M. Boker and J. Graham's (1998) differential structural equation modeling
      approach was expanded to the case of a nonlinear coupled oscillator that is
      common in bimanual coordination studies in which participants swing hand-held
      pendulums but is also applicable to social systems in general. The authors'
      nonlinear coupled oscillator model decomposed the fluctuations into a competitive
      component, unique to each individual variable, and a cooperative component that
      captured bidirectional influence. The authors' model also generated an index of
      the symmetry/asymmetry of bidirectional influence. Together, the models are
      useful quantitative tools for the study of interacting, changing processes.

PMID- 15998176
TI  - Use of the extreme groups approach: a critical reexamination and new
      recommendations.
AB  - Analysis of continuous variables sometimes proceeds by selecting individuals on
      the basis of extreme scores of a sample distribution and submitting only those
      extreme scores to further analysis. This sampling method is known as the extreme
      groups approach (EGA). EGA is often used to achieve greater statistical power in
      subsequent hypothesis tests. However, there are several largely unrecognized
      costs associated with EGA that must be considered. The authors illustrate the
      effects EGA can have on power, standardized effect size, reliability, model
      specification, and the interpretability of results. Finally, the authors discuss
      alternative procedures, as well as possible legitimate uses of EGA. The authors
      urge researchers, editors, reviewers, and consumers to carefully assess the
      extent to which EGA is an appropriate tool in their own research and in that of
      others.

PMID- 15998177
TI  - IRT-related factor analytic procedures for testing the equivalence of paper-and
      pencil and Internet-administered questionnaires.
AB  - This article describes a general item response theory-based factor analytic
      procedure that allows assessment of the equivalence between 2 administrative
      modes of a questionnaire: paper and pencil, and Internet based. The theoretical
      relations between the present procedure and other methods used in previous
      empirical research are shown, and the advantages of the procedure are discussed.
      An empirical application based on 2 personality questionnaires is given, and the
      results are compared with the results of using traditional procedures for
      assessing equivalence. The substantive implications of the results, as well as
      suggestions for further research and methodology, are discussed.

PMID- 15998178
TI  - The correction for attenuation due to measurement error: clarifying concepts and
      creating confidence sets.
AB  - The correction for attenuation due to measurement error (CAME) has received many
      historical criticisms, most of which can be traced to the limited ability to use
      CAME inferentially. Past attempts to determine confidence intervals for CAME are
      summarized and their limitations discussed. The author suggests that inference
      requires confidence sets that demarcate those population parameters likely to
      have produced an obtained value--rather than indicating the samples likely to be
      produced by a given population--and that most researchers tend to confuse these 2
      types of confidence sets. Three different Monte-Carlo methods are presented, each
      offering a different way of examining confidence sets under the new
      conceptualization. Exploring the implications of these approaches for CAME
      suggests potential consequences for other statistics.

PMID- 15998179
TI  - Meta-analytic methods of pooling correlation matrices for structural equation
      modeling under different patterns of missing data.
AB  - Three methods of synthesizing correlations for meta-analytic structural equation
      modeling (SEM) under different degrees and mechanisms of missingness were
      compared for the estimation of correlation and SEM parameters and goodness-of-fit
      indices by using Monte Carlo simulation techniques. A revised generalized least
      squares (GLS) method for synthesizing correlations, weighted-covariance GLS (W
      COV GLS), was compared with univariate weighting with untransformed correlations
      (univariate r) and univariate weighting with Fisher's z-transformed correlations
      (univariate z). These 3 methods were crossed with listwise and pairwise deletion.
      Univariate z and W-COV GLS performed similarly, with W-COV GLS providing slightly
      better estimation of parameters and more correct model rejection rates. Missing
      not at random data produced high levels of relative bias in correlation and model
      parameter estimates and higher incorrect SEM model rejection rates. Pairwise
      deletion resulted in inflated standard errors for all synthesis methods and
      higher incorrect rejection rates for the SEM model with univariate weighting
      procedures.

PMID- 15998180
TI  - Quantifying precision and availability of location memory in everyday pictures
      and some implications for picture database design.
AB  - The authors investigated whether memory for object locations in pictures could be
      exploited to address known difficulties of designing query languages for picture
      databases. M. W. Lansdale's (1998) model of location memory was adapted to 4
      experiments observing memory for everyday pictures. These experiments showed that
      location memory is quantified by 2 parameters: a probability that memory is
      available and a measure of its precision. Availability is determined by
      controlled attentional processes, whereas precision is mostly governed by picture
      composition beyond the viewer's control. Additionally, participants' confidence
      judgments were good predictors of availability but were insensitive to precision.
      This research suggests that databases using location memory are feasible. The
      implications of these findings for database design and for further research and
      development are discussed.

PMID- 15998181
TI  - The predictive validity of self-efficacy in training performance: little more
      than past performance.
AB  - Past research on the influence of self-efficacy in training has provided mixed
      results. Key differences between studies pertain to whether past performance is
      operationalized as a residual variable or as an unadjusted variable and to the
      type of task used. In this study, the authors conducted and performed a
      reanalysis to examine the influence of self-efficacy using both
      operationalizations of past performance in 2 experimental tasks. Results indicate
      that, regardless of task version or type, self-efficacy predicted performance
      only when a residual measure of past performance was used, but not when past
      performance was unadjusted. However, when past performance was adjusted, the
      findings for self-efficacy were likely a statistical artifact. These results
      suggest that self-efficacy is a consequence rather than a cause of performance in
      training.

PMID- 15998182
TI  - The relative effectiveness of various instructional approaches in developing
      anticipation skill.
AB  - The relative effectiveness of explicit instruction, guided discovery, and
      discovery learning techniques in enhancing anticipation skill in young,
      intermediate-level tennis players was examined. Performance was assessed pre- and
      postintervention, during acquisition, and under transfer conditions designed to
      elicit anxiety through the use of laboratory and on-court measures. The 3
      intervention groups improved from pre- to posttest compared with a control group
      (n = 8), highlighting the benefits of perceptual-cognitive training. Participants
      in the explicit (n = 8) and guided discovery (n = 10) groups improved their
      performance during acquisition at a faster rate than did the discovery learning
      (n = 7) group. However, the explicit group showed a significant decrement in
      performance when tested under anxiety provoking conditions compared with the
      guided discovery and discovery learning groups. Although training facilitated
      anticipation skill, irrespective of the type of instruction used in this
      experiment, guided discovery methods are recommended for expediency in learning
      and resilience under pressure.

PMID- 15998183
TI  - Disability and sunshine: can hedonic predictions be improved by drawing attention
      to focusing illusions or emotional adaptation?
AB  - People frequently mispredict the long-term emotional impact of circumstances. The
      authors examine 2 causes of such mispredictions-a focusing illusion and
      underappreciation of adaptation. In Experiment 1, the authors found, in 852
      adults, that quality of life estimates (for living with disability) were not
      increased by reducing focusing illusions. In Experiment 2, the authors found, in
      698 adults, that people's disability estimates were increased by asking them to
      reflect on adaptation. In Experiment 3, the authors found, across 312 Midwestern
      college students, that both approaches reduced the participants' predictions of
      the life satisfaction of their peers living in southern California. In the case
      of living in a better climate, the results suggest that attention to either cause
      influences people's predictions, whereas in the case of chronic disability, the
      results suggest that it is easier to get people to appreciate adaptation than it
      is to reduce focusing illusions.

PMID- 15998184
TI  - Evolving judgments of terror risks: foresight, hindsight, and emotion.
AB  - The authors examined the evolution of cognitive and emotional responses to terror
      risks for a nationally representative sample of Americans between late 2001 and
      late 2002. Respondents' risk judgments changed in ways consistent with their
      reported personal experiences. However, they did not recognize these changes,
      producing hindsight bias in memories for their judgments. An intensive debiasing
      procedure failed to restore a foresightful perspective. A fear-inducing
      manipulation increased risk estimates, whereas an anger-inducing manipulation
      reduced them-both in predictions (as previously observed) and in memories and
      judgments of past risks. Thus, priming emotions shaped not only perceptions of an
      abstract future but also perceptions of a concrete past. These results suggest
      how psychological research can help to ensure an informed public.

PMID- 15998185
TI  - Developmental study of the hippocampal formation in rhesus monkeys (Macaca
      mulatta): I. Early ablations spare discrimination learning but not recognition
      memory.
AB  - In clinical cases of amnesia that followed bilateral excisions of medial temporal
      lobe structures, with some perceptual learning abilities intact, damage to the
      hippocampus was presumed to be the critical factor. The authors' search for an
      animal model of amnesia, based on ablations aimed at the hippocampal formation in
      infant rhesus monkeys, provides support for this view. Ablations of the
      hippocampal formation in 2-month-old infants tested shortly after recovery from
      surgery resulted in a deficit on a recognition memory task but left intact the
      ability to learn the concurrent object discrimination task, even though the
      latter task was administered with the use of a massed practice procedure. Thus,
      early damage, unlike that at 2 years of age or later, allowed the authors to
      dissociate associative learning with repeated trials, independent of hippocampal
      functions and recognition memory that depends on the integrity of the
      hippocampus.

PMID- 15998186
TI  - Developmental study of the hippocampal formation in rhesus monkeys (Macaca
      mulatta): II. Early ablations do not spare the capacity to retrieve conditional
      object-object associations.
AB  - A companion article (see record 2005-06959-001) revealed that hippocampectomy in
      infancy spares concurrent discrimination learning but not recognition memory. The
      present report describes the results obtained with a more complex task,
      conditional object- object association, in which rhesus monkeys (Macaca mulatta)
      had to first learn to discriminate between pairs of objects rather than single
      ones and to subsequently remember which particular object had been a member of a
      rewarded stimulus pair (contextual retrieval). Hippocampectomized infants
      obtained normal scores in learning individual pair discriminations, but they were
      severely impaired in contextual retrieval. The results are interpreted in terms
      of a dual-system theory proposed by R. Hirsh (1974). The results point out not
      only the importance of age at testing but also the nature of the task. The
      authors were also able to glimpse possible instances of cooperation or
      competition between the 2 systems.

PMID- 15998187
TI  - Conditional motor learning in the nonspatial domain: effects of errorless
      learning and the contribution of the fornix to one-trial learning.
AB  - Conditional motor learning contributes importantly to behavioral flexibility. In
      previous work, the authors found that fornix transections impaired the ability of
      macaque monkeys (Macaca mulatta) to learn conditional motor associations between
      the nonspatial features of visual stimuli and nonspatially differentiated
      responses. In the present study, they found that significant 1-trial learning of
      such associations also depended on the fornix. Furthermore, removal of the
      hippocampus, subiculum, and subjacent parahippocampal cortex, added to fornix
      transection, had no effect, thus demonstrating that fornix transections
      eliminated the contribution of the hippocampal system. In addition, the authors
      examined the effect of errorless learning and found, in control monkeys, that
      errors made prior to the 1st correct response retarded 1-trial learning.

PMID- 15998188
TI  - Reinstatement of conditioned fear in humans is context dependent and impaired in
      amnesia.
AB  - A contextual reinstatement procedure was developed to assess the contributions of
      environmental cues and hippocampal function in the recovery of conditioned fear
      following extinction in humans. Experiment 1 showed context specificity in the
      recovery of extinguished skin conductance responses after presentations of an
      auditory unconditioned stimulus. Experiment 2 demonstrated that fear recovery did
      not generalize to an explicitly unpaired conditioned stimulus. Experiment 3
      replicated the context dependency of fear recovery with a shock as an
      unconditioned stimulus. Two amnesic patients failed to recover fear responses
      following reinstatement in the same context, despite showing initial fear
      acquisition. These results extend the known functions of the human hippocampus
      and highlight the importance of environmental contexts in regulating the
      expression of latent fear associations.

PMID- 15998189
TI  - Habit learning and the genetics of the dopamine D3 receptor: evidence from
      patients with schizophrenia and healthy controls.
AB  - In this study, the authors investigated the relationship between the Ser9Gly (SG)
      polymorphism of the dopamine D3 receptor (DRD3) and striatal habit learning in
      healthy controls and patients with schizophrenia. Participants were given the
      weather prediction task, during which probabilistic cue-response associations
      were learned for tarot cards and weather outcomes (rain or sunshine). In both
      healthy controls and patients with schizophrenia, participants with Ser9Ser (SS)
      genotype did not learn during the early phase of the task (1-50 trials), whereas
      participants with SG genotype did so. During the late phase of the task (51-100
      trials), both participants with SS and SG genotype exhibited significant
      learning. Learning rate was normal in patients with schizophrenia. These results
      suggest that the DRD3 variant containing glycine is associated with more
      efficient striatal habit learning in healthy controls and patients with
      schizophrenia.

PMID- 15998190
TI  - Are individual differences in fatigue vulnerability related to baseline
      differences in cortical activation?
AB  - Recent evidence suggests that underlying patterns of cortical activation may
      partially account for individual differences in susceptibility to the effects of
      sleep deprivation. Here, functional magnetic resonance imaging (fMRI) was used to
      examine the activation of military pilots whose sleep-deprivation vulnerability
      previously was quantified. A Sternberg Working Memory Task (SWMT; S. Sternberg,
      1966) was completed alternately with a control task during a 13-min blood oxygen
      level-dependent fMRI scan. Examination of the activated voxels in response to
      SWMT indicated that, as a group, the pilots were more similar to fatigue
      resistant nonpilots than to fatigue-vulnerable nonpilots. Within the pilots,
      cortical activation was significantly related to fatigue vulnerability on
      simulator-flight performance. These preliminary data suggest that baseline fMRI
      scan activation during a working memory task may correlate with fatigue
      susceptibility.

PMID- 15998191
TI  - Ambient odors influence the amplitude and time course of visual distraction.
AB  - Behavioral performance was examined in a task of attentional capture by luminance
      under conditions of ambient odors (phenyl ethyl alcohol [PEA], olfactory
      stimulus, and allyl isothiocyanate [AIC], mixed olfactory/trigeminal stimulus).
      The AIC increased the amplitude and duration of capture, whereas the presence of
      PEA led capture to disappear. Furthermore, the PEA caused a general slowing in
      the speed of information processing. The amplitude and time course of capture
      were correlated to the irritating components of these odorants, whereas a control
      experiment showed that the general slowing caused by the PEA was correlated to a
      drop-off of the subjects' arousal level. These results suggest that ambient odors
      may exert differential influence of visual-attentional processes and that this
      influence may depend on the odor's properties.

PMID- 15998192
TI  - Olfactory conditioned partner preference in the female rat.
AB  - Paced copulation induces conditioned place preference in female rats. The authors
      examined whether associating almond-scented males with paced copulation induces
      conditioned partner preference. The paired group received 4 paced copulations
      with almond-scented males and 4 nonpaced copulations with unscented males
      sequentially at 4-day intervals. The unpaired group received the opposite order
      of association, whereas the randomly paired group received random associations. A
      4th group received a single pairing. On the final test, females were placed into
      an open field with 2 males, 1 scented and 1 unscented. Females in the paired
      group solicited the scented male more frequently, and most chose the scented male
      for their 1st ejaculation. Thus, an odor paired with paced copulation elicits
      conditioned partner preference in female rats.

PMID- 15998193
TI  - A redefinition of odor mixture quality.
AB  - Odor mixtures are perceived as different from (configural) or the same as
      (elemental) their components. Recent studies (L. M. Kay, C. A. Lowry, & H. A.
      Jacobs, 2003; C. Wiltrout, S. Dogra, & C. Linster, 2003) propose that component
      structural or perceptual similarities predict configural properties of binary
      mixtures. The authors evaluated this in rats using 4 binary mixtures with varying
      structural similarity (eucalyptol-benzaldehyde, eugenol-benzaldehyde, octanol
      octanal, and [+/-]-limonene). The range of tested ratios for each mixture was
      determined by the components' vapor pressures. Three results are presented: (a)
      No mixture maintains purely elemental or configural properties for all
      concentration ratios, (b) structural similarity or dissimilarity does not predict
      configural or elemental perception, and (c) overshadowing is significant in
      responses to all odor sets. The authors offer more precise definitions of
      elemental and configural properties and overshadowing as they relate to odor
      mixture perception.

PMID- 15998194
TI  - Tinnitus and hearing loss in hamsters (Mesocricetus auratus) exposed to loud
      sound.
AB  - Hamsters were trained to go left and right to sounds on their left and right
      sides, respectively. Silent trials were occasionally given in which no sound was
      presented. Hamsters exposed to a loud 2- or 10-kHz tone in 1 ear often shifted
      their responding on the silent trials to the side of the exposed ear, suggesting
      that they perceived a sound in that ear (i.e., tinnitus). The degree of tinnitus
      was related to the degree of the accompanying hearing loss (estimated by the
      auditory brainstem response). However, a conductive hearing loss (plugging 1 ear)
      did not cause a hamster to test positive for tinnitus. Tinnitus could be
      demonstrated within minutes following tone exposure, indicating an immediate
      onset, as occurs in humans.

PMID- 15998195
TI  - Wake-promoting actions of medial basal forebrain beta2 receptor stimulation.
AB  - The locus coeruleus-noradrenergic system exerts an activating influence on
      forebrain neuronal and behavioral activity states, in part, through the actions
      of noradrenergic beta receptors located within the medial septal (MS) and medial
      preoptic (MPOA) areas. The current study examined the extent to which beta2
      receptors located within these medial basal forebrain regions modulate behavioral
      state. In this study, the sleep-wake effects of microinfusion of the beta2
      agonist, clenbuterol, into the MS and MPOA were examined. Clenbuterol infusion
      into both MS and MPOA elicited a dose-dependent increase in time spent awake.
      These observations indicate that medial basal forebrain beta-sub-2 receptors
      participate in the noradrenergic-dependent modulation of behavioral state.

PMID- 15998196
TI  - Intracerebroventricular self-administration of commonly abused anabolic
      androgenic steroids in male hamsters (Mesocricetus auratus): nandrolone,
      drostanolone, oxymetholone, and stanozolol.
AB  - Previous studies by the authors have shown voluntary intracerebroventricular
      (icv) testosterone self-administration in hamsters (Mesocricetus auratus). Here,
      the authors compared icv self-administration of 4 anabolic steroids
      (drostanolone, nandrolone, oxymetholone, and stanozolol) at 0.1, 1.0, and 2.0
      microg/microl, each for 8 days. Males (n=8/group) showed the highest levels of
      operant behavior for injectable steroids (drostanolone, nandrolone) compared with
      orally active androgens (oxymetholone, stanozolol). For nandrolone, responses on
      the active and inactive nose-pokes averaged 22.3 +/- 4.6/4 hr and 10.7 +/- 2.0/4
      hr, respectively. Responding for drostanolone was similar. Males self
      administering oxymetholone or stanozolol did not prefer the active nose-poke.
      These data demonstrate that injectable androgens are more reinforcing than oral
      steroids.

PMID- 15998197
TI  - Patterns of brain activation associated with contextual conditioning to
      methamphetamine in mice.
AB  - Classical conditioning is thought to play a key role in addiction. The authors
      used c-Fos immunohistochemistry to demonstrate a conditioned physiological
      response to methamphetamine (meth) in mice. Male outbred mice were placed into an
      environment where they had previously experienced 2 mg/kg meth or saline. The
      meth-paired mice displayed increased c-Fos in several brain regions, including
      the nucleus accumbens, prefrontal cortex, orbitofrontal cortex, basolateral
      amygdala, and bed nucleus of the stria terminalis. No conditioned locomotor
      activity was observed, but individual activity levels strongly correlated with c
      Fos in many regions. A batch effect among immunohistochemical assays was
      demonstrated. Results implicate specific brain regions in classical conditioning
      to meth and demonstrate the importance of considering locomotor activity and
      batch in a c-Fos study.

PMID- 15998198
TI  - Stimulus processing and associative learning in Wistar and WKHA rats.
AB  - This study assessed basic learning and attention abilities in Wistar-Kyoto
      hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures
      of conditioned responding to a visual stimulus, orienting behavior (rearing on
      the hind legs), and food cup behavior (placing the head inside the recessed food
      cup) were measured. In Experiment 1, simple conditioning, but not extinction, was
      impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced
      presentations of the visual cue preceded the conditioning sessions. WKHA rats
      displayed less orienting behavior than Wistar rats but comparable levels of food
      cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in
      attentional processing as well as in learning stimulus-reward relationships.

PMID- 15998199
TI  - The role of CA1 in the acquisition of an object-trace-odor paired associate task.
AB  - This experiment was designed to determine whether adding a temporal component to
      an object-odor association task would recruit the hippocampus. The rats were
      given CA1, CA3, or control lesions prior to learning the object-trace-odor task.
      Rats were presented with an object for 10 s, after which the object was removed,
      followed by a 10-s trace period, followed by the presentation of an odor 50 cm
      away. If the odor and the object were paired, rats were to dig in the odor cup
      for a reward. If unpaired, rats were to refrain from digging. Rats that had CA1
      lesions were unable to make the association, whereas rats that had CA3 lesions
      performed as well as controls. These results support the idea that the
      hippocampus is involved in forming arbitrary associations that do not necessarily
      involve space as long as they involve a temporal component.

PMID- 15998200
TI  - Impairing forgetting by preventing new learning and memory.
AB  - Two causes of forgetting have been promulgated: memory trace decay and
      retroactive interference. The authors show that forgetting is an active process
      requiring both new learning and memory. In the present (1)Lymnaea model system,
      prevention of new learning of a conflicting association, inhibition of memory
      consolidation, or Right Pedal Dorsal 1 soma ablation, which blocks LTM formation,
      are all potent means to prevent forgetting. Thus procedures that alter the
      ability to learn or form memory of a new conflicting aerial respiratory
      association prevent forgetting of a learned associative behavior. These results
      are the 1st demonstration in any model system that forgetting requires the soma
      of a single neuron.

PMID- 15998201
TI  - Out of context: NMDA receptor antagonism in the avian 'prefrontal cortex' impairs
      context processing in a conditional discrimination task.
AB  - Processing of context information is implicated in prefrontal functions as
      response selection or attention. N-methyl-D-aspartate (NMDA) receptors in the
      mammalian prefrontal cortex (PFC) and in the nidopallium caudolaterale (NCL) of
      birds, the avian functional equivalent of the PFC, are involved in learning,
      which also requires processing of context. The authors investigated the role of
      NMDA receptors in the pigeon (Columba livia) NCL for context processing and
      response selection in a simultaneous-matching-to-sample task with 2 trial types,
      requiring either processing of context information, delivered by a conditional
      stimulus (context dependent), or only recall of a stimulus-response association
      (fixed response). The competitive NMDA antagonist DL-2-amino-5-phosphonovaleric
      acid impaired performance only in context-dependent trials. Therefore, NMDA
      receptors in the avian PFC participate in response selection requiring context
      processing rather than in response selection per se.

PMID- 15998202
TI  - Differential fos expression following aspiration, electrolytic, or excitotoxic
      lesions of the perirhinal cortex in rats.
AB  - The authors explored the possibility that there are different neural
      consequences, beyond the primary site of brain damage, following perirhinal
      cortex (PRh) lesions made in different ways. Fos expression was used as a marker
      for neuronal activation and compared across the forebrains of rats that underwent
      the different types of surgery. Electrolytic and excitotoxic PRh lesions produced
      dramatic increases in Fos expression in the cortex, and excitotoxic and
      aspiration PRh lesions increased Fos expression in the dentate gyrus. These data
      are consistent with the hypothesis that different lesion methods have separable
      effects on neural function in regions outside the lesion site that could account
      for inconsistencies in the literature regarding the behavioral effects of PRh
      lesions on tests of spatial memory.

PMID- 15998203
TI  - Neonatal amygdala lesions affect appetitive motivational and consummatory aspects
      of social behavior in the rat.
AB  - In the present study, rats received amygdala lesions (AMX) on either Postnatal
      Day 7 (PD 7; immature brain) or PD 21 (almost mature brain), and adult social
      activity was studied after short-term isolation housing. Sham-operated rats
      demonstrated increased following and approaching behavior after 7 days of
      isolation compared with after 4 days of isolation, an effect that was absent in
      AMX-PD 7 and AMX-PD 21 rats. Furthermore, AMX-PD 7 rats, but not AMX-PD 21 rats,
      displayed a reduction in investigatory behavior after prolonged isolation. This
      indicates that in AMX-PD 21 rats, mainly appetitive motivational aspects of
      social behavior were affected, whereas in AMX-PD 7 rats both motivational and
      consummatory aspects were disturbed. Finally, the reported deficits in AMX-PD 7
      rats may reflect neurodevelopmental deficits of structures connected with the
      amygdala.

PMID- 15998204
TI  - The serotonergic agonists quipazine, CGS-12066A, and alpha-methylserotonin alter
      motor activity and induce hindlimb stepping in the intact and spinal rat fetus.
AB  - The effects of serotonergic agonists were examined in intact and spinal fetuses,
      using an in vivo fetal rat preparation. On Gestational Day 20, fetuses were
      prepared with a midthoracic or sham spinal transection. Dose-response curves were
      obtained for quipazine (nonselective 5-hydroxytryptamine [5-HT] agonist; 1.0-10.0
      mg/kg), CGS-12066A (5-HT-sub(1B) agonist; 1.0-30.0 mg/kg), and alpha
      methylserotonin (alpha-Me-5-HT; 5-HT-sub-2 agonist; 0.2-15.0 mg/kg). During a 10
      min test, each of the agonists (delivered via intraperitoneal injection)
      influenced fetal behavior: They increased the occurrence of head movements,
      mouthing, and hindlimb stepping. Quipazine and alpha-Me-5-HT also promoted
      hindlimb activity in spinal fetuses. Thus, stimulation of the fetal 5-HT system
      modulates motor activity at multiple levels of the developing central nervous
      system.

PMID- 15998205
TI  - Lesions of the dorsal hippocampus block trace fear conditioned potentiation of
      startle.
AB  - Several studies show that the hippocampus is critical for the memories mediating
      trace and contextual fear conditioning. This study investigates whether N-methyl
      D-aspartate-induced lesions of the dorsal hippocampus made prior to training
      affect context fear conditioning and trace fear conditioning measured with the
      fear-potentiated startle. Pretraining excitotoxic lesions of the dorsal
      hippocampus blocked acquisition of trace fear conditioning to a tone stimulus but
      did not affect context fear conditioning. These data indicate that without a
      dorsal hippocampus rats are unable to acquire trace conditioning but can acquire
      contextual fear when fear is measured by potentiation of the startle response.

PMID- 15998206
TI  - Discrimination of multidimensional visual stimuli by mice: intra- and
      extradimensional shifts.
AB  - A visual discrimination protocol similar to that used with monkeys was adapted to
      measure attentional set-shifting in mice. An automated touchscreen procedure with
      compound visual stimuli was used to train mice to attend to 1 of 2 stimulus
      dimensions (lines or shapes). On a 2nd problem with new stimuli, the mice were
      required to attend to the same dimension (intradimensional [ID] shift) or switch
      to the previously irrelevant dimension (extradimensional [ED] shift). Mice
      readily learned the initial compound discrimination and following shift problem,
      but there was no ID-ED difference. The fact that mice can be tested with stimuli
      and task sequences similar to those used with primates suggests that this method
      can be used to directly compare higher cognitive functions in diverse species.

PMID- 15998207
TI  - Commentary: In vitro-cultured meat production.

PMID- 15998208
TI  - Viability and osteogenic potential of cryopreserved human bone marrow-derived
      mesenchymal cells.
AB  - Human bone marrow-derived mesenchymal cells contain mesenchymal stem cells
      (MSCs), which are well known for their osteo/chondrogenic potential and can be
      used for bone reconstruction. This article reports the viability of cryopreserved
      human mesenchymal cells and a comparison of the osteogenic potential between
      noncryopreserved and cryopreserved human mesenchymal cells with MSC-like
      characteristics, derived from the bone marrow of 28 subjects. The viability of
      cryopreserved mesenchymal cells was approximately 90% regardless of the storage
      term (0.3 to 37 months). It is clear by fluorescence-activated cell sorter
      analysis that the cell surface antigens of both noncryopreserved and
      cryopreserved mesenchymal cells were negative for hematopoietic cell markers such
      as CD14, CD34, CD45, and HLA-DR but positive for mesenchymal characteristics such
      as CD29 and CD105. To monitor the osteogenic potential of the cells, such as
      alkaline phosphatase (ALP) activity and in vitro mineralization, a subculture was
      conducted in the presence of dexamethasone, ascorbic acid, and glycerophosphate.
      No difference in osteogenic potential was found between cells with or without
      cryopreservation treatment. In addition, cells undergoing long-term
      cryopreservation (about 3 years) maintained high osteogenic potential. In
      conclusion, cryopreserved as well as noncryopreserved human mesenchymal cells
      could be applied for bone regeneration in orthopedics.

PMID- 15998209
TI  - Optimization of dynamic culture conditions: effects on biosynthetic activities of
      chondrocytes grown in collagen sponges.
AB  - Application of mechanical stimulation, using dynamic bioreactors, is considered
      an effective strategy to enhance cellular behavior in load-bearing tissues. In
      this study, two types of perfusion mode (direct and free flow) are investigated
      in terms of the biosynthetic activities of chondrocytes grown in collagen sponges
      by assessment of cell proliferation rate, matrix production, and tissue
      morphology. Effects of the duration of preculture and dynamic conditioning are
      further determined. Our results have demonstrated that both bovine and human
      derived chondrocytes demonstrate a dose-dependent response to flow rate (0-1
      mL/min) in terms of cell number and glycosaminoglycan (GAG) content. This may
      reflect the weak adhesion of cells to the sponge scaffolds and the immature state
      of the constructs even after 3 weeks of proliferative culture. Our studies define
      an optimal flow rate between 0.1 and 0.3 mL/min for direct perfusion and free
      flow bioreactors. Using fresh bovine chondrocytes and a lower flow rate of 0.1
      mL/min, a comparison was made between free flow system and direct perfusion
      system. In the free flow bioreactor, no cell loss was observed and higher GAG
      production was measured compared with static cultured controls. However, as with
      direct perfusion, the enhancement effect of free flow perfusion was strongly
      dependent on the maturation and organization of the constructs before the
      stimulation. To address the maturation of the matrix, preculture periods were
      varied before mechanical conditioning. An increase in culture duration of 18 days
      before mechanical conditioning resulted in enhanced GAG production compared with
      controls. Interestingly, additional enhancement was found in specimens that were
      further subjected to a prolonged duration of perfusion (63% increase after an
      additional 4 days of perfusion) after prematuration. The free flow system has an
      advantage over the direct perfusion system, especially when using sponge
      scaffolds, which have lower mechanical properties; however, mass transfer of
      nutrients is still more optimal throughout the scaffolds in a direct perfusion
      system as demonstrated by histological analysis.

PMID- 15998210
TI  - Calcified matrix production by SAOS-2 cells inside a polyurethane porous
      scaffold, using a perfusion bioreactor.
AB  - The repair and regeneration of damaged or resected bone are problematic. Bone
      autografts show optimal skeletal incorporation, but often bring about
      complications. Hence, there is increasing interest in designing new biomaterials
      that could potentially be used in the form of scaffolds as bone substitutes. In
      this study we used a hydrophobic cross-linked polyurethane in a typical tissue
      engineering approach, that is, the seeding and in vitro culturing of cells within
      a porous scaffold. The polyurethane porous scaffold had an average pore diameter
      of 624 microm. Using a perfusion bioreactor, we investigated the effect of shear
      stress on SAOS-2 human osteoblast proliferation and calcified matrix production.
      The physical, morphological, and compressive properties of the polyurethane foam
      were characterized. At a scaffold perfusion rate of 3 mL/min, in comparison with
      static conditions without perfusion, we observed 33% higher cell proliferation;
      higher secretion of osteopontin, osteocalcin, decorin, and type I collagen (9.16
      fold, 71.9-fold, 30.6-fold, and 18.12-fold, respectively); and 10-fold increased
      calcium deposition. The design of the bioreactor and the design of the
      polyurethane foam aimed at obtaining cell colonization and calcified matrix
      deposition. This cultured biomaterial could be used, in clinical applications, as
      an osteoinductive implant for bone repair.

PMID- 15998211
TI  - Cell patterning on biological gels via cell spraying through a mask.
AB  - We present an easily applicable and inexpensive method for patterning cells on
      arbitrary surfaces including biological gels with little loss of viability or
      function. Single-cell suspensions of human umbilical vein endothelial cells and
      NIH 3T3 fibroblasts were sprayed with an off-the-shelf airbrush through a mask to
      create 100-microm scale patterns on collagen gels. Three-dimensional patterns
      were created by layering a collagen gel on top of the first pattern and
      patterning the top gel. Coculture of rat hepatocytes with NIH 3T3 patterns on
      collagen gels resulted in localized increased activity of cytochrome P-450 along
      the pattern. These results suggest that cell spraying is a useful tool for the
      study of heterotypic cellular interactions and tissue-engineering applications on
      biologically relevant matrices, and for the creation of three-dimensional cell
      patterns in vitro.

PMID- 15998212
TI  - Follicle-like model by granulosa cell encapsulation in a barium alginate
      protamine membrane.
AB  - Granulosa cells from bovine and porcine ovaries were cultured either in monolayer
      or in follicle-like barium alginate capsules for 6 days. Morphological
      investigation by electron scanning microscopy indicated that culture in a three
      dimensional (3D) system allows self-organization of spherical-polyhedral shape
      cells. The luteinization index (progesterone:17beta-estradiol ratio) was
      significantly higher for monolayer cells than for the 3D cell culture system,
      confirming the results of morphological analysis and indicating more
      physiological growth. The encapsulated 3D culture system appears to be a
      promising way of obtaining in vitro maturation and development of follicles and
      oocytes.

PMID- 15998213
TI  - Vascular endothelial growth factor-releasing scaffolds enhance vascularization
      and engraftment of hepatocytes transplanted on liver lobes.
AB  - Hepatocyte transplantation within porous scaffolds (HT) is being explored as a
      treatment strategy for end-stage liver diseases and enzyme deficiencies. One of
      the main issues in this approach is the limited viability of transplanted cells
      because vascularization of the scaffold site is either too slow or insufficient.
      We now address this by enhancing scaffold vascularization before cell
      transplantation via sustained delivery of vascular endothelial growth factor
      (VEGF), and by examining the liver lobes as a platform for transplanting donor
      hepatocytes in close proximity to the host liver. The vascularization kinetics of
      unseeded VEGF-releasing scaffolds on rat liver lobes were evaluated by analyzing
      the microvascular density and tissue ingrowth in implants harvested on days 3, 7,
      and 14 postimplantation. Capillary density was greater at all times in VEGF
      releasing scaffolds than in the control scaffold without VEGF supplementation; on
      day 14, it was 220 +/- 33 versus 139 +/- 23 capillaries/mm2 (p < 0.05).
      Furthermore, 35% of the newly formed capillaries in VEGF-releasing scaffolds were
      larger than 16 microm in diameter, whereas in control scaffolds only 10% exceeded
      this size. VEGF had no effect on tissue ingrowth into the scaffolds. HT onto the
      implanted VEGF-releasing or control scaffolds was performed after 1 week of
      prevascularization on the liver lobe in Lewis rats. Fifty implants were harvested
      on days 1, 3, 7, and 12 and the area of viable hepatocytes was evaluated. The
      enhanced vascularization improved hepatocyte engraftment; 12 days after HT, the
      intact hepatocyte area (136,910 microm2/cross-section) in VEGF-releasing
      scaffolds was 4.6 higher than in the control group. This study shows that
      sustained local delivery of VEGF induced vascularization of porous scaffolds
      implanted on liver lobes and improved hepatocyte engraftment.

PMID- 15998214
TI  - Optimization and characterization of an engineered human skin equivalent.
AB  - Skin equivalents (SEs) have been designed to meet both basic and applied research
      needs. The successful application of tissue-engineered SEs requires that the
      reconstituted tissues be endowed with the correct organization and function. A
      large body of experimental evidence now supports the notion that the inducing
      effects of mesenchymal tissue on epithelial cell morphogenesis are mediated, at
      least in part, by extracellular matrix components in addition to cell-cell
      interactions. A coculture model including both fibroblasts and keratinocytes was
      used to study the effects of progressive serum reduction on epidermal
      differentiation, quality of dermal and dermal-epidermal junctions, and expression
      of extracellular matrix proteins. The cells were successively added to a dermal
      substrate composed of collagen, glycosaminoglycans, and chitosan. The main aim of
      this study was to optimize this model for pharmacotoxicological trials. Control
      skin equivalents were cultured with medium containing 10% serum throughout the
      production process. Serum content was reduced to 1 and 0% at the air-liquid
      interface and compared with control skin equivalents. First, we demonstrated that
      serum deprivation at the air-liquid interface improves keratinocyte terminal
      differentiation. Second, we showed that, in the absence of serum, the specific
      characteristics of the SE are maintained, including epidermal and dermal
      ultrastructure, the expression of major dermal extracellular matrix components
      (human collagen types I, III, and V, fibronectin, elastin, and fibrillin 1), and
      the dermal-epidermal junction (laminin, human type IV collagen, alpha6 integrin).
      Furthermore, our results indicate that coculture models using keratinocytes and
      fibroblasts have both morphological and functional properties required for
      biologically useful tissues.

PMID- 15998215
TI  - Cytomimetic engineering of hepatocyte morphogenesis and function by substrate
      based presentation of acellular E-cadherin.
AB  - Although cadherin-mediated intercellular contacts can be integral to the
      maintenance of functionally competent hepatocytes in vitro, the ability to
      engineer hepatocellular differentiated function via acellular E-cadherin has yet
      to be thoroughly explored. To investigate the potential of substrate-presented,
      acellular E-cadherin to modulate hepatocellular self-assembly and functional
      fate, rat hepatocytes were cultured at sparse densities on surfaces designed to
      display recombinant E-cadherin/Fc chimeras. On these substrates, hepatocytes were
      observed to recognize microdisplayed E-cadherin/Fc and responded by modulating
      the spatial distribution of the intracellular cadherin-complexing protein beta
      catenin. Substrate-presented E-cadherin/Fc was also found to markedly alter
      patterns of hepatocyte morphogenesis, as cellular spreading and two-dimensional
      reorganization were significantly inhibited under these conditions, leading to
      multicellular aggregates that were considerably more three-dimensional in nature.
      Increasing cadherin exposure was also associated with elevated levels of albumin
      and urea secretion, two markers of hepatocyte differentiation, over control
      cultures. This suggested that cell-substrate cadherin engagement established more
      functionally competent hepatocellular phenotypes, coinciding with the notion that
      E-cadherin is a differentiation-inducing ligand for these cells. The
      morphogenetic and function-promoting effects of substrate-bound E-cadherin/Fc
      were further enhanced under conditions in which protein A was utilized as an
      anchoring molecule to present cadherin molecules, suggesting that ligand mobility
      may play an important role in the effective establishment of cell-to-substrate
      cadherin interactions. Interestingly, the percent increase in function detected
      for conditions of high cadherin exposure versus control cultures was found to be
      substantially higher at extremely low cell densities. This observation indicated
      that hepatocytes respond to substrate-presented E-cadherin even in the absence of
      native intercellular interactions and associated juxtacrine signaling. The
      incorporation of acellular E-cadherin on biomaterial substrates may thus
      potentially present a means to prevent hepatocellular dedifferentiation by
      maintaining liver-specific function in otherwise severely functionally repressive
      culture conditions.

PMID- 15998216
TI  - Preservation and regeneration of alveolar bone by tissue-engineered implants.
AB  - Bone maintenance after dental extraction has a significant impact on the success
      of future treatment. The purpose of this study was to regenerate bone by
      implanting an engineered porous scaffold seeded with bone marrow mesenchymal stem
      cells (BMSCs) in a socket created by extraction of the lower left central incisor
      in rabbits, utilizing the principles of tissue engineering. It involved
      preparation and characterization of three-dimensional porous hollow root form
      scaffolds consisting of a poly-L-lactic acid:polyglycolic acid composite (PLG,
      50:50), using a solvent casting/compression molding/particulate leaching
      technique. Porosity of the scaffolds was 83.71% with good interconnectivity and
      uniform distribution of the various pore sizes. The degraded scaffolds maintained
      their porosity and form for the first 2 weeks and their mass loss continued up to
      6 weeks. The scaffolds developed viscoelastic behavior under dynamic compression;
      yet they lost their mechanical characteristics as they degraded. The scaffolds
      were seeded with BMSCs and examined by scanning electron microscopy. Cell
      proliferation and scaffold degradation were shown up to 2 weeks in vitro. The
      cultivated scaffolds were implanted in empty extraction sockets immediately after
      tooth removal. Four weeks later, bone regeneration was evaluated histologically
      in the healed sockets in three experimental groups: sockets left empty, sockets
      that received PLG without cells, and sockets that received PLG with cells.
      Radiographic evaluation, performed 4 weeks later for the three experimental
      groups, demonstrated preservation of alveolar bone walls in the extraction
      sockets that received PLG with cells as compared with the other two groups. The
      bone density profile for the healed sockets confirmed both histological and
      radiographic findings. The results of this study show promise in the area of
      dentoalveolar surgery, yet longitudinal studies under variable clinical
      situations would encourage the current application.

PMID- 15998217
TI  - Bioactive glass stimulates the secretion of angiogenic growth factors and
      angiogenesis in vitro.
AB  - Neovascularization of tissue-engineered constructs remains a limiting factor for
      the engineering of larger tissue constructs. Attempts to stimulate
      neovascularization, using recombinant protein or gene transfer of angiogenic
      growth factors, have been proposed; however, these approaches have been
      associated with problems regarding the delivery and duration of exposure of the
      growth factor. This study was performed to determine the ability of biologically
      active glass to stimulate the secretion of angiogenic growth factors from human
      stromal cells and subsequent angiogenesis. CCD18Co human fibroblasts were
      cultured on tissue culture surfaces coated with specific quantities of 45S5
      Bioglass particles. At 24-, 48-, and 72-h intervals the gene expression of
      vascular endothelial growth factor (VEGF) and the protein secretion of VEGF and
      basic fibroblast growth factor (bFGF) from fibroblasts were measured. The effect
      of conditioned medium collected from Bioglass-stimulated fibroblasts on human
      dermal microvascular endothelial cells was assessed using in vitro angiogenesis
      assays. Results showed that surfaces coated with Bioglass produced a significant
      increase in the secretion of VEGF and bFGF. Conditioned medium from stimulated
      fibroblasts significantly increased the proliferation of human dermal
      microvascular endothelial cells and induced a significant increase in the
      formation of anastomosed networks of human endothelial cell tubules. It is
      concluded that the ability of 45S5 Bioglass to stimulate the release of
      angiogenic growth factors and to promote angiogenesis provides a novel
      alternative approach for stimulating neovascularization of tissue-engineered
      constructs.

PMID- 15998218
TI  - Tissue engineering of recellularized small-diameter vascular grafts.
AB  - A tissue-engineered small-diameter arterial graft would be of benefit to patients
      requiring vascular reconstructive procedures. Our objective was to produce a
      tissue-engineered vascular graft with a high patency rate that could withstand
      arterial pressures. Rat arteries were acellularized with a series of detergent
      solutions, recellularized by incubation with a primary culture of endothelial
      cells, and implanted as interposition grafts in the common femoral artery.
      Acellular grafts that had not been recellularized were implanted in a separate
      group of control animals. No systemic anticoagulants were administered. Grafts
      were explanted at 4 weeks for definitive patency evaluation and histologic
      examination; 89% of the recellularized grafts and 29% of the control grafts
      remained patent. Elastin staining demonstrated the preservation of elastic fibers
      within the media of the acellular grafts before implantation. Immunohistochemical
      staining of explanted grafts demonstrated a complete layer of endothelial cells
      on the lumenal surface in grafts that remained patent. Smooth muscle cells were
      observed to have repopulated the vessel walls. The mechanical properties of the
      matrix were comparable to native vessels. Such a strategy may present an
      alternative to autologous harvest of small vessels for use in vascular bypass
      procedures.

PMID- 15998219
TI  - Role of adult mesenchymal stem cells in bone tissue engineering applications:
      current status and future prospects.
AB  - Mesenchymal stem cells (MSCs) have been demonstrated as an attractive cell source
      for tissue-engineering applications because of their ability to be easily
      isolated and expanded from adult bone marrow aspirates and their versatility for
      pluripotent differentiation into mesenchymal tissues. This review highlights
      advances and progress in bone reconstruction techniques for both the repair of
      site-specific bone defects and the attenuation of musculoskeletal disease
      symptoms associated with osteoporosis and osteogenesis imperfecta. Despite the
      enormous potential benefits of MSCs within these approaches, conventional tissue
      culture methods limit the clinical utility of these cells because of the gradual
      loss of both their proliferative and differentiation potential during ex vivo
      expansion. Novel strategies to overcome these limitations are discussed including
      cultivation in the presence of basic fibroblastic growth factor 2, induction of
      ectopotic telomerase expression, and ex vivo expansion on various collagenous
      biomaterials. In addition, this review also outlines mechanistic theories on the
      potential role of MSC-extracellular matrix interactions in mediating the
      retention of MSC proliferative and differentiation capacity after ex vivo
      expansion on collagenous biomaterials.

PMID- 15998220
TI  - Myocardial engineering in vivo: formation and characterization of contractile,
      vascularized three-dimensional cardiac tissue.
AB  - Engineering cardiac tissue in three dimensions is limited by the ability to
      supply nourishment to the cells in the center of the construct. This limits the
      radius of an in vitro engineered cardiac construct to approximately 40 microm.
      This study describes a method of engineering contractile three-dimensional
      cardiac tissue with the incorporation of an intrinsic vascular supply. Neonatal
      cardiac myocytes were cultured in vivo in silicone chambers, in close proximity
      to an intact vascular pedicle. Silicone tubes were filled with a suspension of
      cardiac myocytes in fibrin gel and surgically placed around the femoral artery
      and vein of adult rats. At 3 weeks, the tissues in the chambers were harvested
      for in vitro contractility evaluation and processed for histologic analysis. By 3
      weeks, the chambers had become filled with living tissue. Hematoxylin and eosin
      staining showed large amounts of muscle tissue situated around the femoral
      vessels. Electron micrographs revealed well-organized intracellular contractile
      machinery and a high degree of intercellular connectivity. Immunostaining for von
      Willebrand factor demonstrated neovascularization throughout the constructs. With
      electrical stimulation, the constructs were able to generate an average active
      force of 263 microN with a maximum of 843 microN. Electrical pacing was
      successful at frequencies of 1 to 20 Hz. In addition, the constructs exhibited
      positive inotropy in response to ionic calcium and positive chronotropy in
      response to epinephrine. As engineering of cardiac replacement tissue proceeds,
      vascularization is an increasingly important component in the development of
      three-dimensional structures. This study demonstrates the in vivo survival,
      vascularization, organization, and functionality of transplanted myocardial
      cells.

PMID- 15998221
TI  - De novo reconstruction of functional bone by tissue engineering in the metatarsal
      sheep model.
AB  - Large bone defects are still a challenge to orthopedic surgeons. In this study, a
      massive bone defect with a clinically relevant volume was efficiently
      reconstructed by transplanting an engineered bone in which mesenchymal stem cells
      (MSCs) expanded in autologous serum (AS) were combined with a porous scaffold. In
      the first step, we established that the way in which the MSCs are distributed
      over the scaffold affects the ultimate bone-forming ability of the transplant:
      constructs consisting of a natural coral scaffold and a pseudo-periosteal layer
      of MSCs surrounding the implant (coral-MSC3D) formed significantly more bone than
      constructs in which the MSCs were distributed throughout the implant (p = 0.01).
      However, bone healing occurred in only one sheep, owing to the high resorption
      rate of natural coral scaffold. To overcome this problem, constructs in which
      MSCs were combined with a porous coralline-based hydroxyapatite (CHA) scaffold
      having the same architecture as natural coral but a lower resorption rate were
      prepared. After their implantation, these constructs were found to have the same
      osteogenic potential as autologous bone grafts in terms of the amount of newly
      formed bone present at 4 months (p = 0.89) and to have been completely replaced
      by newly formed, structurally competent bone within 14 months. Nevertheless,
      although the rate of bone healing was strikingly improved when CHA-MSC3D
      constructs were used (five of seven animals healed) as compared with the coral
      MSC3D construct (one of seven healed), it was still less satisfactory than that
      obtained with autografts (five of five healed).

PMID- 15998222
TI  - Alignment of osteoblast-like cells and cell-produced collagen matrix induced by
      nanogrooves.
AB  - Alignment of bone cells and collagen matrix is closely related to the anisotropic
      mechanical properties of bone. Intact scaffolds that promote osteoblast
      differentiation and mineralization in the preferred direction offer promise in
      the generation of biomimetic bone tissue. In this study, we examined the
      alignment of osteoblast-like cells and collagen fibers guided by nanogrooves.
      Nanoscale groove-ridge patterns (approximately 300 nm in periodicity, 60-70 nm in
      depth) on the surface of polystyrene (PS) were made by polarized Nd:YAG laser
      irradiation, at a wavelength of 266 nm. The influence of such "nanoscale
      features" on the orientation and alignment of cells and their mineralized
      collagen matrix was investigated, using rabbit mesenchymal stem cell (MSC)
      derived osteoblast-like cells. The cells and actin stress fibers were aligned and
      elongated along the direction of the nanogrooves. In addition, the alignment of
      collagen matrix was also influenced by underlying nanogrooves. The results
      suggested that nanoscale fibrous cues in the longitudinal direction might
      contribute to the aligned formation of bone tissue. This may provide an effective
      approach for constructing biomimetic bone tissue.

PMID- 15998223
TI  - Loading of a novel angiogenic agent, ginsenoside Rg1 in an acellular biological
      tissue for tissue regeneration.
AB  - In this study, the effects of ginsenoside Rg1, a natural compound isolated from
      Panax ginseng, on human umbilical vein endothelial cell (HUVEC) behavior in
      vitro, and on angiogenesis and tissue regeneration in genipin-fixed acellular
      tissue (extracellular matrix, ECM) in vivo, were investigated. Basic fibroblast
      growth factor (bFGF) was used as a control. The in vitro results indicated that
      in the presence of bFGF or Rg1, HUVEC proliferation was significantly increased.
      Both bFGF and Rg1 promoted HUVEC migration in a Transwell plate assay. In
      addition, bFGF or Rg1 significantly increased the formation of capillary-like
      network by HUVECs on Matrigel. Thus, both bFGF and Rg1 enhanced multiple
      components of angiogenic activity in vitro. The in vivo results obtained 1 week
      postoperatively showed that the extent of angiogenesis in ECMs was significantly
      enhanced by bFGF or Rg1. At 1 month postoperatively, vascularized neoconnective
      tissues were found to fill the pores within ECMs loaded with bFGF or Rg1. There
      was a significant increase in neocapillary density from 1 week to 1 month for
      ECMs loaded with Rg1, whereas that observed in ECMs loaded with bFGF stayed
      approximately the same because of the limitations of protein stability. These
      results suggested that Rg1 may be a new class of angiogenic agent and may be
      loaded in ECMs to accelerate tissue regeneration.

PMID- 15998224
TI  - Biocompatible nanofiber matrices for the engineering of a dermal substitute for
      skin regeneration.
AB  - Natural and synthetic biodegradable nanofibers are extensively used for
      biomedical applications and tissue engineering. Biocompatibility and a well
      established safety profile for polycaprolactone (PCL) and collagen represent a
      favorable matrix for preparing a dermal substitute for engineering skin. Collagen
      synthesized by fibroblasts is a good surface active agent and demonstrates its
      ability to penetrate a lipid-free interface. During granulation tissue formation,
      fibronectin provides a temporary substratum for migration and proliferation of
      cells and provides a template for collagen deposition, which increases stiffness
      and tensile strength of this healing tissues. The objective of this study was to
      fabricate nanofiber matrices from novel biodegradable PCL and collagen to mimic
      natural extracellular matrix (ECM) and to examine the cell behavior, cell
      attachment, and interaction between cells and nanofiber matrices. Collagen
      nanofiber matrices show a significant (p < 0.001) level of fibroblast
      proliferation and increase up to 54% compared with control tissue culture plate
      (TCP) after 72 h. The present investigation shows that PCL-coated collagen
      matrices are suitable for fibroblast growth, proliferation, and migration inside
      the matrices. This novel biodegradable PCL and collagen nanofiber matrices
      support the attachment and proliferation of human dermal fibroblasts and might
      have potential in tissue engineering as a dermal substitute for skin
      regeneration.

PMID- 15998225
TI  - Differentiation of osteoblasts in three-dimensional culture in processed
      cancellous bone matrix: quantitative analysis of gene expression based on real
      time reverse transcription-polymerase chain reaction.
AB  - Processed bovine cancellous bone (PBCB) is an attractive material for tissue
      engineering of bone. It is biocompatible, osteoconductive, nonimmunogenic, and
      porous and its biomechanical properties are close to those of native bone. In
      this study, differentiation of primary rat osteoblasts (rOBs) incubated on PBCB
      was investigated in vitro. rOBs were isolated and expanded in two-dimensional
      culture. Expanded rOBs were seeded into PBCB disks and cultured either in basal
      medium (BM) or differentiation medium (DM) containing ascorbic acid, beta
      glycerol phosphate, and dexamethasone. Alkaline phosphatase (ALP) activity and
      RNA expression of ALP, bone sialoprotein (BSP), collagen type I (COL1),
      osteocalcin (OC), and osteopontin (OPN) were assessed by chemiluminescence assay
      and quantitative real-time RT-PCR over 14 days. Histologic analysis was performed
      on day 14. ALP increased over the observation period independent of stimulation.
      OPN and BSP expression was significantly higher in the DM group whereas COL1 and
      OC expression was significantly higher in the BM group. Matrix calcification was
      detectable only in the DM group by von Kossa stain. The observed expression
      patterns suggest a physiological response of rOBs to the differentiation
      stimulus. PBCB is a suitable matrix for in vitro differentiation of osteoblasts.
      Cell-seeded PBCB is a potential osteogenic construct for in vivo application.

PMID- 15998226
TI  - Integrin dimerization and ligand organization: key components in integrin
      clustering for cell adhesion.
AB  - Cell adhesion requires both integrin occupancy and integrin clustering. In this
      work, we investigate a mechanism based on organizing ligand into islands and
      integrin dimerization for the initiation of integrin clustering. To study
      integrin clustering and integrin occupancy we develop a two-dimensional Monte
      Carlo lattice description of the cell-substrate interface to simulate the
      diffusion and reaction of integrins. We demonstrate that integrin dimerization
      can drive integrins into clusters of sizes greater than two. Ligand organization
      or integrin dimerization alone is unable to increase the number of bound
      integrins, but when both are present they cooperate to increase both binding and
      clustering of integrins. In addition, when integrin dimerization and ligand
      organization are both present large integrin clusters, which may act as
      nucleation sites for the formation of adhesion complexes, are observed. These
      results describe a potential mechanism for the clustering of integrin receptors
      and avidity modulation in cellular adhesion and have implications for the designs
      of surfaces to control cell responses to external ligands and to manipulate cell
      adhesion for tissue-engineering applications.

PMID- 15998227
TI  - Behavior of human articular chondrocytes derived from nonarthritic and
      osteoarthritic cartilage in a collagen matrix.
AB  - The purpose of this study was to evaluate the morphologic and biochemical
      behavior and activity of human chondrocytes taken from nonarthritic and
      osteoarthritic cartilage and seeded on a three-dimensional matrix consisting of
      collagen types I, II, and III. Human articular chondrocytes were isolated from
      either nonarthritic or osteoarthritic cartilage of elderly subjects, and from
      nonarthritic cartilage of an adolescent subject, seeded on collagen matrices, and
      cultured for 12 h, 7 days, and 14 days. Histological analysis,
      immunohistochemistry, and biochemical assays for glycosaminoglycans (GAGs) and
      DNA content were performed for cell-seeded and unseeded matrices. Chondrocytes of
      nonarthritic cartilage revealed a larger number of spherical cells, consistent
      with a chondrocytic phenotype. The biochemical assay showed a net increase in GAG
      content in nonarthritic chondrocytes, whereas almost no GAGs were seen in
      osteoarthritic cells. The DNA results suggest that more osteoarthritic cells than
      chondrocytes from nonarthritic cartilage attached to the matrix within the first
      week. Human articular chondrocytes isolated from osteoarthritic cartilage seem to
      have less bioactivity after expansion and culture in a sponge consisting of type
      I, II, and III collagen compared with chondrocytes from nonarthritic cartilage.

PMID- 15998228
TI  - Enhanced endothelial cell retention on shear-stressed synthetic vascular grafts
      precoated with RGD-cross-linked fibrin.
AB  - Clinical in vitro endothelialization has been shown to increase the patency of
      synthetic vascular grafts. The shear stress resistance of the cultured autologous
      endothelium represents a crucial cornerstone of the concept. We investigated
      whether an enrichment of the precoating matrix with adhesion sites can augment
      endothelial cell attachment. Adult human saphenous vein endothelial cells
      (AHSVECs) were seeded confluently ([58 +/- 11] x 10(3) AHSVECs/cm2) onto 10-cm
      long ePTFE (expanded polytetrafluorethylene) vascular grafts (n = 24) precoated
      with commercial clinically approved fibrin gel (Tisseal) containing various
      concentrations of cross-linked RGD peptide (0.0, 4.0, 8.0, or 16.0 mg of RGD per
      milliliter of Tisseal fibrinogen component). Endothelialized grafts were
      postcultivated for 9 days before they were exposed to a pulsatile circulation
      model mimicking peak physiological shear stress conditions of the femoral artery
      (12 dyn/cm2; min/max, -60/+28 dyn/cm2). Cell loss after 24 h was quantitatively
      determined by image analysis of vital stains. Initial 24-h cell loss was 27.2 +/-
      1.7% in grafts precoated with the non-RGD-enriched fibrin matrix. In contrast,
      cell loss was significantly less on fibrin containing 4.0 mg of RGD peptide per
      milliliter of Tisseal fibrinogen component (13.3 +/- 7.9%; p < 0.05). Cell loss
      on fibrin containing 8 and 16 mg of RGD per milliliter of Tisseal fibrinogen
      component was 41.0 +/- 27.4 and 43.0 +/- 23.2% (p > 0.05), respectively. We
      conclude that low concentrations of RGD peptide cross-linked into commercial
      fibrin matrices used for clinical in vitro lining of vascular grafts led to
      significantly increased endothelial cell retention. The failure of higher RGD
      concentrations to enhance endothelial cell attachment may be explained by
      competitive binding of endothelial cells to non-cross-linked RGD.

PMID- 15998229
TI  - Bone marrow stromal cells can provide a local environment that favors migration
      and formation of tubular structures of endothelial cells.
AB  - Findings suggest that mesenchymal progenitor cells can support the process of
      blood vessel formation, which may be relevant during granulation tissue formation
      at defect sites. The aim of this study was to investigate possible mechanisms of
      the angiogenic process that can be stimulated by mesenchymal progenitor cells. In
      the in vivo-like model of the chick embryo chorioallantoic membrane assay, we
      observed blood vessel ingrowth into collagen sponges containing conditioned
      medium from undifferentiated bone marrow stromal cells. In the Boyden chamber
      assay, the conditioned medium was chemotactic for human umbilical vascular
      endothelial cells and human uterus microvascular endothelial cells, and when
      cells were placed on Matrigel-coated culture dishes, formation of tubular
      structures was enhanced. The presence of vascular endothelial growth factor
      neutralizing antibodies did not affect the outcome of the two in vitro assays.
      Bone marrow stromal cell-conditioned medium had no effect on proliferation of
      endothelial cells, as determined by measuring [3H]thymidine incorporation, and on
      matrix metalloproteinase 2 expression, as evaluated by reverse transcription
      polymerase chain reaction and gelatin zymography. These data indicate that
      mesenchymal progenitor cells can provide a local environment that supports the
      ingrowth of blood vessels into a defect site.

PMID- 15998230
TI  - Comparative study of the ability of mesenchymal stem cells derived from bone
      marrow, periosteum, and adipose tissue in treatment of partial growth arrest in
      rabbit.
AB  - This study evaluates the ability of MSCs isolated from different origins--bone
      marrow, periosteum, or fat--to treat partial growth arrest in immature (6-week
      old) New Zealand White rabbits. Up to 50% of the medial half of the proximal
      physis of the tibia was excised in these New Zealand White rabbits. Three weeks
      later, the bony bridge was excised, and fibrin glue with and without MSCs were
      transferred into the physeal defect of different rabbits. Contralateral tibias,
      without undergoing operation, served as self-control. Four groups of rabbits were
      involved in the study. Each group was injected separately with bone marrow
      derived MSCs (group I), periosteum-derived MSCs (group II), fat-derived MSCs
      (group III), and fibrin glue alone (control, group IV). The rabbits were killed 8
      and 16 weeks postoperatively. Clinical, radiological, and histological analyses
      were subsequently performed. Similar proliferative rates for three MSCs were
      demonstrated on days 4, 7, and 11 of primary culture. However, MSCs derived from
      bone-marrow and periosteum appeared to be more homogeneous than that from fat.
      All MSCs demonstrated chondrogenic and osteogenic differentiation potentials in
      vitro. The tibias in groups I and II showed significant correction of varus
      angulation at 16 weeks. However, the varus angulation in group III remained
      significantly obvious when compared with group I (p < 0.05). The length
      discrepancies between operated and normal tibiae in groups I, II, and III were
      significantly corrected compared with control (p < 0.01). In conclusion, bone
      marrow and periosteum yielded more homogenous MSCs than fat, providing better
      correction of physeal arrest in rabbits. The source of MSCs itself could
      influence the success in the treatment of growth arrest.

PMID- 15998231
TI  - Treatment of complete spinal cord injury patients by autologous bone marrow cell
      transplantation and administration of granulocyte-macrophage colony stimulating
      factor.
AB  - Transplantation of bone marrow cells into the injured spinal cord has been found
      to improve neurologic functions in experimental animal studies. However, it is
      unclear whether bone marrow cells can similarly improve the neurologic functions
      of complete spinal cord injury (SCI) in human patients. To address this issue, we
      evaluated the therapeutic effects of autologous bone marrow cell transplantation
      (BMT) in conjunction with the administration of granulocyte macrophage-colony
      stimulating factor (GM-CSF) in six complete SCI patients. BMT in the injury site
      (1.1 x 10(6) cells/microL in a total of 1.8 mL) and subcutaneous GM-CSF
      administration were performed on five patients. One patient was treated with GM
      CSF only. The follow-up periods were from 6 to 18 months, depending on the
      patients. Sensory improvements were noted immediately after the operations.
      Sensory recovery in the sacral segment was noted mainly 3 weeks to 7 months
      postoperatively. Significant motor improvements were noted 3 to 7 months
      postoperatively. Four patients showed neurologic improvements in their American
      Spiral Injury Association Impairment Scale (AIS) grades (from A to C). One
      patient improved to AIS grade B from A and the last patient remained in AIS grade
      A. No immediate worsening of neurologic symptoms was found. Side effects of GMCSF
      treatment such as a fever (>38 degrees C) and myalgia were noted. Serious
      complications increasing mortality and morbidity were not found. The follow-up
      study with magnetic resonance imaging 4-6 months after injury showed slight
      enhancement within the zone of BMT. Syrinx formation was not definitely found.
      BMT and GM-CSF administration represent a safe protocol to efficiently manage SCI
      patients, especially those with acute complete injury. To demonstrate the full
      therapeutic value of this protocol, long-term and more comprehensive case-control
      clinical studies are required.

PMID- 15998232
TI  - Effect of transforming growth factor beta 2 on marrow-infused foam poly(propylene
      fumarate) tissue-engineered constructs for the repair of critical-size cranial
      defects in rabbits.
AB  - This study investigates the osseointegration of poly(propylene fumarate) (PPF)
      with beta-tricalcium phosphate (beta-TCP) scaffolds in a critical-size (diameter,
      1.6 cm), cranial defect in 4-month-old rabbits (n = 51), killed at 6 or 12 weeks.
      Two molecular weights of PPF were used to produce bilayer scaffolds with 0.5-mm
      solid external and 2.0-mm porous internal layers. The porous layer was infused
      with bone marrow aspirate, with half the animals receiving 0.8 microg of
      transforming growth factor beta2 (TGF-beta2). No foreign body or inflammatory
      response was observed externally or on histological examination of explants.
      Statistical analysis of histological areal and linear measures of new bone
      formation found significantly more bone at the later sacrifice time, followed by
      implants receiving TGF-beta2, followed by low molecular weight PPF implants.
      Approximately 40% of the explants were tested for incorporation strength with a
      one-point "push-in" test. Because no permanent fixation was used, implant
      strength (28.37-129.03 N; range, 6.4 to 29.0 lb of resistance) was due entirely
      to new bone formation. The strongest bone was seen in implants receiving TGF
      beta2-infused marrow in animals killed at 12 weeks. These results support the use
      of PPF as an osteogenic substrate and future research into preoperative
      fabrication of critical size and supercritical-size cranial prosthetic implants.

PMID- 15998233
TI  - Astrocyte growth and glial cell line-derived neurotrophic factor secretion in
      three-dimensional polyethylene terephthalate fibrous matrices.
AB  - The ability of human astrocytes grown in nonwoven fibrous matrices to produce
      glial cell line-derived neurotrophic factor (GDNF) was studied. GDNF has the
      ability to selectively nourish and regenerate dopaminergic neurons and thus can
      provide a new treatment of Parkinson's disease. Compressed polyethylene
      terephthalate (PET) fabrics (porosity, 88.8%; mean pore diameter, 64 microm),
      treated with boiling NaOH, was effective in supporting high-density growth of
      astrocytes with stable GDNF production over the entire period of 18 days studied.
      Treatment of PET with NaOH renders the fiber surface more hydrophilic, thereby
      facilitating attachment and spreading of cells, whereas matrix compression allows
      cells to grow along and also between the fibers of these matrices to a higher
      density. The average production of GDNF by cells grown in these matrices
      (approximately 2 cm in diameter) was 21.7 pg/mL x day, with an average high
      concentration of 64.6 pg/mL, which is well above the effective concentration of
      40 pg/mL. This work shows promise in culturing astrocytes in PET matrices as the
      first step in developing a potential implantable tissue-engineering device for
      treating patients with Parkinson's disease.

PMID- 15998234
TI  - In vivo response of polylactic acid-alginate scaffolds and bone marrow-derived
      cells for cartilage tissue engineering.
AB  - Successful application of tissue-engineering techniques to damaged biological
      structures is determined by functional performance in vivo. This study evaluated
      the in vivo response of a tissue-engineered construct composed of a polylactic
      acid-alginate amalgam seeded with bone marrow-derived mesenchymal stem cells and
      stimulated in vitro with transforming growth factor beta for cartilage tissue
      engineering. Constructs were placed in cylindrical osteochondral defects in the
      canine femoral condyle and examined 6 weeks postoperatively by gross,
      histological, immunohistochemical, and biomechanical analyses. In the course of 6
      weeks in vivo, the defects filled with a cartilaginous tissue regardless of
      whether cell-seeded (experimental) or cell-free (control) constructs were
      implanted; however, the quality of the tissue differed between the experimental
      and control defects. Cell-seeded experimental defects showed more cartilage-like
      matrix quality, cell distribution, and proteoglycan staining. Biomechanically,
      experimental and control specimens exhibited similar behavior; however, both
      tissues were still immature compared with normal cartilage. The evidence
      accumulated in this study showed a modest acceleration of the in vivo healing of
      cell-seeded constructs but also demonstrated a reparative response of cell-free
      constructs. This finding suggests that the constructs prepared from the PLA
      alginate amalgam may serve as a means for host cell attachment.

PMID- 15998235
TI  - Macrophage adhesion on gelatin-based interpenetrating networks grafted with
      PEGylated RGD.
AB  - Human blood-derived macrophage adhesion on interpenetrating networks (IPNs)
      composed of PEGylated RGD-modified gelatin and poly(ethylene glycol) diacrylate
      was studied. The interaction between biomaterial immobilized with biofunctional
      peptides such as RGD and macrophages is central in the design of tissue
      engineering scaffolds. PEGylated RGD-modified gelatin was synthesized via several
      steps involving PEG derivations and characterized by high-performance liquid
      chromatography, mass spectroscopy, gel permeation chromatography, and the
      trinitrobenzenesulfonic acid method. IPNs containing modified or unmodified
      gelatin were cultured with human macrophages and monitored at 2, 24, 96, and 168
      h. At each time point, IPNs containing gelatin modified with PEGylated RGD showed
      a comparable adherent macrophage density as tissue culture polystyrene and a
      significantly higher cell density than other IPN formulations containing
      unmodified gelatin or gelatin modified with PEGylated triglycine. Although
      surface-immobilized RGD can serve to mediate the adhesion of different cell types
      on the biomaterial surface, the interaction of RGD with immune/inflammatory cells
      such as macrophages should also be considered when assessing the potential host
      response of tissue-engineering scaffolds.

PMID- 15998236
TI  - Pluronic F127 as a cell encapsulation material: utilization of membrane
      stabilizing agents.
AB  - Thermoreversible gelation of the copolymer Pluronic F127 (generic name, poloxamer
      407) in water makes it a unique candidate for cell encapsulation applications,
      either alone or to promote cell seeding and attachment in tissue scaffolds. At
      concentrations of 15-20% (w/w), aqueous Pluronic F127 (F127) solutions gel at
      physiological temperatures. The effect of F127 on viability and proliferation of
      human liver carcinoma cells (HepG2) was determined for both liquid and gel
      formulations. Cell concentration and viability over a 5-day period were measured
      by the trypan blue assay via hemocytometry and results were confirmed in both the
      MTT and LDH assays. With 0.1-5% (w/w) F127 (liquid), cells proliferated and
      maintained high viability over 5 days. However, at 10% (w/w) F127 (liquid), there
      was a significant decrease in cell viability and no cell proliferation was
      evident. HepG2 cell encapsulation in F127 concentrations ranging from 15 to 20%
      (w/w) (gel) resulted in complete cell death by 5 days. This was also true for the
      HMEC-1 (endothelial) and L6 (muscle) cell lines evaluated. Cell-seeding density
      did not affect cell survival or proliferation. Membrane-stabilizing agents
      (hydrocortisone, glucose, and glycerol) were added to the F127 gel formulations
      to improve cell viability. The steroid hydrocortisone demonstrated the most
      significant improvement in viability, from <2% (in F127 alone) to >70% (with 60
      nM hydrocortisone added). These results suggest that F127 formulations
      supplemented with membrane-stabilizing agents can serve as viable cell
      encapsulation materials. In addition, hydrocortisone may be generally useful in
      the promotion of cell viability for a wide range of encapsulation materials.

PMID- 15998238
TI  - Zofenoprilat-glutathione mixed disulfide as a specific S-thiolating agent of
      bovine lens aldose reductase.
AB  - The ability of Zofenoprilat, an angiotensin-converting enzyme inhibitor carrying
      a thiol group, to intervene in protein S-thiolation processes was tested on
      bovine lens aldose reductase (ALR2). Zofenoprilat, more susceptible to oxidation
      than glutathione (GSH), forms with this physiological thiol a rather stable mixed
      disulfide (ZSSG). ZSSG, whose generation through the transthiolation reaction
      between GSH and Zofenoprilat homodisulfide was shown to be enhanced by a micro
      class glutathione S-transferase, appears to be a specific donor of the
      Zofenoprilat moiety in the S-thiolation processes. This is indicated by the
      apparent stability of ZSSG to reduction by GSH and by the specificity of the
      transfer of the group on ALR2, used as a protein model. Indeed, the S-thiolation
      of ALR2 by ZSSG occurred exclusively through the insertion of the Zofenoprilat
      moiety of ZSSG on the enzyme. The modified ALR2 is shown to retain the same
      activity of the native enzyme, but displays a reduced sensitivity to inhibition.
      The S-thiolation of specific target enzymes is proposed as an event potentially
      relevant for the antioxidant action of Zofenoprilat.

PMID- 15998240
TI  - PKC sulfhydryl targeting by disulfiram produces divergent isozymic regulatory
      responses that accord with the cancer preventive activity of the thiuram
      disulfide.
AB  - The protein kinase C (PKC) isozyme family plays key roles in cell growth
      regulation and influences neoplastic disease development and progression. For
      example, PKCepsilon is oncogenic, and PKCdelta tumor-suppressive. PKC isozymes
      are characterized by distinct activation mechanisms entailing phosphatidylserine
      dependent cofactor binding to the regulatory domain. Evidence is now emerging
      that redox signaling offers another platform of PKC regulation. We have
      established that PKC isozymes are regulated by S-thiolation, a posttranslational
      modification entailing disulfide linkage of low-molecular-weight species to
      select protein sulfhydryls. Our recent studies demonstrate that physiologically
      occurring disulfides with cysteinyl constituents, e.g., cystine, regulate
      cellular PKC isozymes by S-thiolation-triggered mechanisms. This report shows
      that PKC isozymes are also molecular targets of a chemically distinct class of
      disulfides. Disulfiram is a thiuram disulfide with potent cancer preventive
      activity in in vivo models of chemical carcinogenesis. Our results indicate that
      PKC Sthiolation by disulfiram induces differential regulatory effects on PKC
      isozymes that correlate with the cancer preventive activity of the drug. The
      implication of these findings is that PKC-regulatory effects of thiuram
      disulfides may offer a useful pharmacological guide for development of disulfiram
      analogues with superior cancer preventive activity.

PMID- 15998239
TI  - Molecular determinants of S-glutathionylation of carbonic anhydrase 3.
AB  - Carbonic anhydrase 3 is easily S-glutathionylated in vivo and in vitro. The
      protein has two surface-exposed cysteine residues that can be modified. We found
      that Cys186 is more readily glutathionylated than Cys181. We studied a series of
      site-specific mutants to identify the residues that interact with Cys186 to make
      its thiol more reactive. We found that Lys211 is responsible for lowering the pKa
      of Cys186. We also found that two acidic residues, Asp188 and Glu212, interact
      with the thiol and actually decrease its reactivity. We speculate that
      conformational changes that alter the interaction with these three residues
      provide a mechanistic basis for modulation of the susceptibility of carbonic
      anhydrase 3 to glutathionylation.

PMID- 15998241
TI  - S-thiolation of tyrosine hydroxylase by reactive nitrogen species in the presence
      of cysteine or glutathione.
AB  - Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme in the
      biosynthesis of the neurotransmitter dopamine. Peroxynitrite (ONOO-) and nitrogen
      dioxide (NO2) inhibit TH catalytic function and cause nitration of protein
      tyrosine residues. Exposure of TH to either ONOO- or NO2 in the presence of
      cysteine (or glutathione) prevents tyrosine nitration and results in S-thiolation
      instead. TH catalytic activity is suppressed by S-thiolation. Dithiothreitol
      prevents and reverses the modification of TH by S-thiolation, and returns enzyme
      activity to control levels. S-Nitrosothiols, which are known to S-thiolate
      proteins, can be formed in the reaction of cysteine or glutathione with reactive
      nitrogen species. Therefore, S-nitrosoglutathione (GSNO) was tested for its
      ability to modify TH. Fresh solutions of GSNO did not modify TH, whereas
      decomposed GSNO resulted in extensive S-thiolation of the protein. Dimedone, a
      sulfenic acid trap, prevents S-thiolation of TH when included with GSNO during
      its decomposition. Taken together, these results show that TH is S-thiolated by
      ONOO- or NO2 in the presence of cysteine. S-Thiolation occurs at the expense of
      tyrosine nitration. Glutathione disulfide S-oxide, which forms spontaneously in
      the decomposition of GSNO and which is found in tissue undergoing oxidative
      stress, may be the species that S-thiolates TH.

PMID- 15998242
TI  - Effects of S-glutathionylation and S-nitrosylation on calmodulin binding to
      triads and FKBP12 binding to type 1 calcium release channels.
AB  - This study shows that the combination of glutathione (GSH) plus hydrogen peroxide
      (H2O2) promotes the S-glutathionylation of ryanodine receptor type 1 (RyR1) Ca2+
      release channels, and confirms their joint S-glutathionylation and S
      nitrosylation by S-nitrosoglutathione (GSNO). In addition, we show that 35S
      labeled 12-kDa FK506-binding protein ([35S]FKBP12) bound with a Kd of 13.1 nM to
      RyR1 present in triads or heavy sarcoplasmic reticulum vesicles; RyR1 S
      nitrosylation by NOR-3 or GSNO, but not S-glutathionylation, specifically
      increased by four- to fivefold this Kd value. RyR1 redox modifications also
      increased the Kd of [35S]calmodulin binding to triads without affecting Bmax.
      RyR1 S-glutathionylation (induced by GSH plus H2O2) or RyR1 S-nitrosylation
      (produced by NOR-3) increased by approximately six- or twofold, respectively, the
      Kd of apocalmodulin (apoCaM) or Ca2+-calmodulin (CaCaM) binding to triads.
      Likewise, the combined S-glutathionylation and S-nitrosylation of RyR1 induced by
      GSNO increased by fourfold the Kd of CaCaM binding to triads and abolished apoCaM
      binding. As both FKBP12 and CaCaM inhibit RyR1, decreased FKBP12 binding to RyR1
      and/or decreased CaCaM binding to either RyR1 or dihydropyridine receptor in
      triad preparations may cause the reported enhanced activation of Ca2+-induced
      Ca2+ release kinetics mediated by S-glutathionylation/S-nitrosylation. We discuss
      possible consequences of these redox modifications on RyR1-mediated Ca2+ release
      in physiological or pathological conditions.

PMID- 15998243
TI  - Ischemic preconditioning: a potential role for protein S-thiolation?
AB  - Oxidant stress plays a crucial role in the triggering of cardioprotection
      involving ischemic preconditioning (IPC). We have used biotin-tagged cysteine to
      probe for redox-modified proteins in IPC protocols. Cysteine was biotinylated and
      introduced into isolated rat hearts. S-Thiolated proteins were detected and
      quantified using nonreducing western blots probed with streptavidin-horseradish
      peroxidase. Controls (15 min of aerobic perfusion plus 5 min of 0.5 mM biotin
      cysteine plus 5 min of aerobic perfusion) showed low-level protein S-thiolation.
      Hearts preconditioned with 5 min of ischemia and reperfused for 5 min with biotin
      cysteine plus 5 min of aerobic perfusion showed increased thiolation (160%) that
      was fully blocked by the antioxidant mercaptopropionylglycine, which is also
      known to block IPC. "Preconditioning" agonists (phorbol 12-myristate 13-acetate
      or phenylephrine) or oxidants (hydrogen peroxide or diamide) administered during
      aerobic preparations to biotin-cysteine-loaded hearts induced efficient protein S
      thiolation. Preconditioning agonist-induced S-thiolation was significantly
      attenuated by diphenyleneiodonium (a flavoprotein inhibitor) or by the protein
      kinase C inhibitor bisindolylmaleimide I. Additional studies testing the role of
      a Nox2-containing NAD(P)H oxidase as the source of the oxidant stress essential
      to the triggering IPC showed that protein S-thiolation was the same in wild-type
      and Nox2 knockout mice.

PMID- 15998244
TI  - NF-kappaB, Nrf2, and HO-1 interplay in redox-regulated VCAM-1 expression.
AB  - Oxidative processes are considered to play a crucial role in the induction of
      cell adhesion molecules, a key event in inflammatory processes. We recently
      reported on an unexpected unidirectional effect of an overexpressed antioxidant
      [phospholipid hydroperoxide glutathione peroxidase (PHGPx)] and an oxidant [15
      lipoxygenase (15-LOX)] enzyme on the basal and interleukin-1 induced vascular
      cell adhesion molecule-1 (VCAM-1) expression in vascular smooth muscle cells
      (SMC). Both enzymes inhibited VCAM-1 expression and reduced the cellular protein
      thiol content, thus, both exerting an oxidant effect. We now investigated whether
      transcription factors known to be regulated by oxidation, i.e., the nuclear
      factor-kappaB and the Keap1/Nrf2 system, were affected in our set of cells: SMC,
      SMC(PHGPx), and SMC(LOX), as well as ECV and ECV(PHGPx). PHGPx and 15-LOX
      inhibited nuclear factor-kappaB activation most efficiently at a step downstream
      of DNA binding, which explains their inhibitory effect on VCAM-1 expression. Both
      enzymes up-regulated endogenous heme oxygenase-1 most probably via activation of
      Nrf2. Transfected Nrf2 strongly inhibited VCAM-1 promoter activity, which could
      be reversed by cotransfection with Keap1. The key player in this complex cross
      talk obviously is heme oxygenase-1, which is known to be induced by oxidant
      activated Nrf2. The moderate oxidative stress initiated by enhanced PHGPx or 15
      LOX activity appears to induce a defense system that diminishes the response to
      further proinflammatory stimuli.

PMID- 15998245
TI  - Glutathione depletion in a midbrain-derived immortalized dopaminergic cell line
      results in limited tyrosine nitration of mitochondrial complex I subunits:
      implications for Parkinson's disease.
AB  - Oxidative stress and mitochondrial dysfunction signify two important biochemical
      events associated with the loss of dopaminergic neurons in Parkinson's disease
      (PD). Studies using in vitro and in vivo PD models and in affected tissues from
      the disease itself have demonstrated a selective inhibition of mitochondrial
      complex I activity that appears to affect normal mitochondrial physiology leading
      to neuronal cell death. Earlier experiments from our laboratory have demonstrated
      that induced depletion of glutathione (GSH + GSSG) in cultured dopaminergic cells
      resulted in increased oxidative stress and a decrease in mitochondrial function.
      Furthermore, this dysfunction was linked to a selective decrease in mitochondrial
      complex I activity that appears to be due to oxidation of this complex.
      Glutathione depletion is the earliest detectable biochemical event during PD
      progression and occurs prior to complex I inhibition. Recent observations have
      also indicated that oxidative damage to complex I via naturally occurring free
      radicals such as peroxynitrite leads to modification of tyrosine and/or cysteine
      residues resulting in complex I inhibition. Using the sucrose gradient method, we
      detected in complex I-enriched fractions from a glutathione-depleted dopaminergic
      cell line two bands corresponding to approximately 25-kDa and approximately 30
      kDa polypeptides that demonstrate anti-nitrotyrosine immunoreactivity, suggesting
      the possible involvement of protein nitration by peroxynitrite in glutathione
      depletion-mediated complex I inhibition.

PMID- 15998246
TI  - The S-thiolating activity of membrane gamma-glutamyltransferase: formation of
      cysteinyl-glycine mixed disulfides with cellular proteins and in the cell
      microenvironment.
AB  - Previous studies have documented that activity of the plasma membrane enzyme
      gamma-glutamyltransferase (GGT) is accompanied by prooxidant processes, with
      production of reactive oxygen species and oxidation of cellular protein thiols.
      The present work was aimed to verify the occurrence and extent of S-thiolation
      mediated by GGT and characterize the molecular species involved in mixed
      disulfide formation. Experiments show that the cysteinyl-glycine (CG) originating
      from cellular GGT-mediated glutathione (GSH) metabolism can efficiently thiolate
      cellular proteins, as well as proteins present in the extracellular environment.
      With cells presenting high levels of GGT expression, basal levels of CG
      containing protein mixed disulfides are detectable, in cellular proteins, as well
      as in proteins of the culture medium. Stimulation of GGT activity in these cells
      by administration of substrates results in an increase of CG mixed disulfide
      formation and a concomitant decrease of GSH-containing disulfides, likely due to
      GGT-dependent removal of GSH from the system. The findings reported suggest that
      binding of CG ("protein S-cysteylglycylation") may represent an as yet
      unrecognized function of membrane GGT, likely playing a regulatory role(s) in the
      cell and its surroundings.

PMID- 15998247
TI  - Identification of plant glutaredoxin targets.
AB  - Glutaredoxins (Grxs) are small ubiquitous proteins of the thioredoxin (Trx)
      family, which catalyze dithiol-disulfide exchange reactions or reduce protein
      mixed glutathione disulfides. In plants, several Trx-interacting proteins have
      been isolated from different compartments, whereas very few Grx-interacting
      proteins are known. We describe here the determination of Grx target proteins
      using a mutated poplar Grx, various tissular and subcellular plant extracts, and
      liquid chromatography coupled to tandem mass spectrometry detection. We have
      identified 94 putative targets, involved in many processes, including oxidative
      stress response [peroxiredoxins (Prxs), ascorbate peroxidase, catalase],
      nitrogen, sulfur, and carbon metabolisms (methionine synthase, alanine
      aminotransferase, phosphoglycerate kinase), translation (elongation factors E and
      Tu), or protein folding (heat shock protein 70). Some of these proteins were
      previously found to interact with Trx or to be glutathiolated in other organisms,
      but others could be more specific partners of Grx. To substantiate further these
      data, Grx was shown to support catalysis of the stroma beta-type carbonic
      anhydrase and Prx IIF of Arabidopsis thaliana, but not of poplar 2-Cys Prx.
      Overall, these data suggest that the interaction could occur randomly either with
      exposed cysteinyl disulfide bonds formed within or between target proteins or
      with mixed disulfides between a protein thiol and glutathione.

PMID- 15998248
TI  - S-nitrosation versus S-glutathionylation of protein sulfhydryl groups by S
      nitrosoglutathione.
AB  - S-Nitrosation of protein sulfhydryl groups is an established response to
      oxidative/nitrosative stress. The transient nature and reversibility of S
      nitrosation, as well as its specificity, render this posttranslational
      modification an attractive mechanism of regulation of protein function and signal
      transduction, in analogy to S-glutathionylation. Several feasible mechanisms for
      protein S-nitrosation have been proposed, including transnitrosation by S
      nitrosothiols, such as S-nitrosoglutathione (GSNO), where the nitrosonium moiety
      is directly transferred from one thiol to another. The reaction between GSNO and
      protein sulfhydryls can also produce a mixed disulfide by S-glutathionylation,
      which involves the nucleophilic attack of the sulfur of GSNO by the protein
      thiolate anion. In this study, we have investigated the possible occurrence of S
      glutathionylation during reaction of GSNO with papain, creatine phosphokinase,
      glyceraldehyde-3-phosphate dehydrogenase, alcohol dehydrogenase, bovine serum
      albumin, and actin. Our results show that papain, creatine phosphokinase, and
      glyceraldehyde-3-phosphate dehydrogenase were significantly both S-nitrosated and
      S-glutathionylated by GSNO, whereas alcohol dehydrogenase, bovine serum albumin,
      and actin appeared nearly only S-nitrosated. The susceptibility of the modified
      proteins to denitrosation and deglutathionylation by reduced glutathione was also
      investigated.

PMID- 15998249
TI  - Cellular and molecular targets of protein S-glutathiolation.
AB  - Oxidative stress and reactive oxygen species play a major role in both normal and
      pathophysiologic cellular processes. Although many cellular constituents can be
      damaged by oxidant exposure, cysteine thiol groups are among the most readily
      oxidized moieties found within cells. To avoid potentially irreversible cysteine
      thiol oxidation, cells have developed multiple antioxidant defenses to preserve
      these moieties. Among these defenses, protein S-glutathiolation has emerged as an
      important mechanism, both in the maintenance of thiol stability during oxidant
      exposure and as a rapid and efficient mechanism regulating protein activity and
      cellular metabolic pathways. Here we review the known molecular targets of S
      glutathiolation, with emphasis on the varying molecular effects of S
      glutathiolation on different proteins.

PMID- 15998250
TI  - Biochemical and biological aspects of protein thiolation in cells and plasma.
AB  - Protein thiolation is elicited by oxidation by different mechanisms and is
      involved in a variety of biological processes. Thiols, protein SH (PSH) and non
      protein SH groups (NPSH, namely GSH), are in competition in all biological
      environments in the regulation of oxidant homeostasis because oxidants thiolate
      proteins, whereas GSH dethiolates them (e.g., GSSG + PSH --> GSSP + GSH).
      Although poorly investigated, the elimination of disulfides from thiolated
      proteins to regenerate critical PSH is important. These aspects are poorly known
      in cells, where glutaredoxin and peroxiredoxin operate as enzymes or potential
      chaperones to accelerate dethiolation. On the contrary, studies with plasma or
      albumin have highlighted the importance of protein conformation in dethiolation
      processes and have clarified the reason why homocysteine (thiol with potential
      toxicity) is preferentially bound to albumin as protein-thiol mixed disulfide
      with respect to other NPSH. Here we provide an overview of protein
      thiolation/dethiolation processes, with an emphasis on recent developments and
      future perspectives in this field.

PMID- 15998251
TI  - Thiol-disulfide balance: from the concept of oxidative stress to that of redox
      regulation.
AB  - Originally, small thiols, including glutathione, were viewed as protective
      antioxidants, acting as free radical scavengers in the context of oxidative
      damage. Recently, there is a growing literature showing that protein
      glutathionylation (formation of protein-glutathione mixed disulfides) and other
      forms of cysteine oxidation may be a means of redox regulation under
      physiological conditions. This review discusses the importance of protein
      oxidation in redox regulation in view of the recent data originating from the
      application of redox proteomics to identify redox-sensitive targets.

PMID- 15998252
TI  - Glutathione-associated regulation of plant growth and stress responses.
AB  - A reduced form of glutathione (GSH) is considered to protect the cell from
      oxidative damage, based on its redox buffering action and abundance in the cell.
      However, in plants, the high redox potential molecule ascorbate exists at
      comparable or higher concentrations and is used for scavenging hydrogen peroxide
      as an electron donor. Recently, examples that cannot be explained simply by the
      antioxidant activity of GSH have been increasing in number. This article
      summarizes the recent findings on the glutathione-associated events in plants, in
      particular, growth and development including cell differentiation, cell death and
      senescence, pathogen resistance, and enzymatic regulation.

PMID- 15998253
TI  - The transfer of reductive energy and pace of proteome turnover: a theory of
      integrated catabolic control.
AB  - Hundreds of cell proteins undergo reversible transitions among redox states.
      Coordinate control and common functions served by redox-modified proteins are
      unknown. The suspect "redox code" integrating metabolome, proteome, and genome
      remains undefined. Protein redox control involves coupling of the population
      redox partition to transfer of reductive energy from source to sink. Lessons in
      metabolic programs under redox coordination might be found in nutritional
      desperation where reductive transfer from fuel fails to feed pathways to protein
      reduction. Upon nutritional interruption, proteolysis initially increases.
      However, catabolism secondarily declines in later starvation so as to postpone
      loss of the minimal proteome under synthetic failure and delay death. Integrated
      proteome turnover is paced by reductive transfer coupled to redox states of
      proteins serving diverse functions. Some continuing proteolysis is redox
      independent. Cathepsin B is a model, redox-responsive, catabolic machine among
      proteins involved in turnover. The CysHis pair is simultaneously a redox
      responsive site, an inhibitory metal-binding site, and a peptidolytic reaction
      mechanism. Pro-region cleavage generates permissive reaction conditions, but not
      necessarily the maximal peptidolytic rate. Mature cathepsin B can be inactivated
      by partition into multiple oxidation states. Cathepsin B can be reductively
      activated by glutathione or disulfhydryl reductases, and redox-buffered by
      glutathione homodisulfide/glutathione. Topics in protease regulation include: (a)
      the rate of total cell transfer of nutrient reductive energy from NADPH source
      potential to reductive pathways, (b) the distribution of reductive energy routed
      through parallel interactive pathways to protease, (c) the rate of transfer from
      protease through pathways to oxygen (reactive oxygen species) acceptor at sink
      potential, and (d) the linkage of protease state partition to relative rates of
      reductions and oxidations. Cell iron, sulfur, and oxygen redox are inseparable.
      The interaction of the CysHis site with iron provides a sensor, integrator, and
      effector switch coupling cathepsin B to metal-sulfuroxygen redox. Artificial
      metal-redox-proton switching is a new concept in protein engineering; however,
      nature has already applied "nanotechnology" to protein redox control.

PMID- 15998254
TI  - Glutathionylation of mitochondrial proteins.
AB  - Many proteins contain free thiols that can be modified by the reversible
      formation of mixed disulfides with low-molecular-weight thiols through a process
      called S-thiolation. As the majority of these modifications result from the
      interaction of protein thiols with the endogenous glutathione pool, protein
      glutathionylation is the predominant alteration. Protein glutathionylation is of
      significance both for defense against oxidative damage and in redox signaling. As
      mitochondria are at the heart of both oxidative damage and redox signaling within
      the cell, the glutathionylation of mitochondrial proteins is of particular
      importance. Here we review the mechanisms and physiological significance of the
      glutathionylation of mitochondrial thiol proteins.

PMID- 15998255
TI  - Redox regulation of insulin action and signaling.

PMID- 15998256
TI  - H2O2-induced phosphorylation of ERK1/2 and PKB requires tyrosine kinase activity
      of insulin receptor and c-Src.
AB  - Hydrogen peroxide (H2O2) mimics many physiological responses of insulin, and
      increased H2O2 generation via the Nox-4 subunit of NAD(P)H oxidase was recently
      demonstrated to serve as a critical early step in the insulin signaling pathway.
      Exogenously added H2O2 has also been shown to activate several key components of
      the insulin signaling cascade. H2O2-induced signaling responses have been found
      to be associated with the activation of receptor and nonreceptor protein tyrosine
      kinases (PTK), including the insulin receptor (IR)-beta subunit. Therefore, in
      the present studies on Chinese hamster ovary cells overexpressing wild-type IR
      PTK (CHO-IR) or a PTK-inactive form of IR (CHO-1018), we investigated whether IR
      PTK plays a role in H2O2-induced signaling events. Treatment of CHO-IR cells with
      H2O2 increased the phosphorylation of extracellular signal-regulated kinases 1
      and 2 (ERK1/2), protein kinase B (PKB), and glycogen synthase kinase-3beta while
      enhancing tyrosine phosphorylation of the IR-beta subunit and the p85 subunit of
      phosphatidylinositol 3-kinase (PI3K). Compared with CHO-IR cells, the stimulatory
      effect of H2O2 on ERK1/2 and PKB was partially reduced in CHO-1018 cells.
      However, pharmacological inhibition of Src family PTK by 4-amino-5-(4
      chlorophenyl)-7-(tert-butyl)pyrazolo[3,4-d]pyrimidine (PP-2) almost completely
      blocked H2O2-stimulated phosphorylation of the p85 subunit of PI3K, ERK1/2, and
      PKB. Moreover, H2O2, but not insulin, induced Tyr-418 phosphorylation of Src,
      which was also suppressed by PP-2. Taken together, these data suggest that both
      IR-PTK and Src family PTKs contribute to H2O2-induced signaling in CHO-IR cells
      albeit IR-PTK has a less dominant role in this process.

PMID- 15998258
TI  - Utilization of the insulin-signaling network in the metabolic actions of alpha
      lipoic acid-reduction or oxidation?
AB  - Alpha-lipoic acid is a naturally occurring cofactor of mitochondrial
      dehydrogenase complexes and a potent antioxidant. It can interchange between a
      reduced form and an oxidized form, thereby displaying reducing (antioxidant) and
      prooxidant properties, respectively. It is suggested that alpha-lipoic acid
      through its prooxidant properties acutely stimulates the insulin-signaling
      cascade, thereby increasing glucose uptake in muscle and fat cells. On the other
      hand, alpha-lipoic acid appears to protect the insulin-signaling cascade from
      oxidative stress-induced insulin resistance through its reducing capacities. In
      addition, alpha-lipoic acid seems to inhibit hepatic gluconeogenesis by
      interfering with fatty acid oxidation, as well as to increase peripheral glucose
      utilization by activating pyruvate dehydrogenase resulting in increased glucose
      oxidation. These different properties render alpha-lipoic acid a potentially
      attractive therapeutic agent for the treatment of insulin resistance. Moreover,
      given the potential role of oxidative stress in the pathogenesis of secondary
      complications in diabetes, alpha-lipoic acid might be beneficial in the
      prevention/treatment of these complications as was recently shown for diabetic
      neuropathy.

PMID- 15998257
TI  - Role of insulin-induced reactive oxygen species in the insulin signaling pathway.
AB  - Oxidants, including hydrogen peroxide (H2O2), have been recognized for years to
      mimic insulin action on glucose transport in adipose cells. Early studies also
      demonstrated the complementary finding that H2O2 was elaborated during treatment
      of cells with insulin, suggesting that cellular H2O2 generation was integral to
      insulin signaling. Recently, reactive oxygen species elicited by various hormones
      and growth factors have been shown to affect signal transduction pathways in
      various cell types. We recently reported that insulin-stimulated H2O2 modulates
      proximal and distal insulin signaling, at least in part through the oxidative
      inhibition of protein tyrosine phosphatases (PTPases) that negatively regulate
      the insulin action pathway. Nox4, a homologue in the family of NADPH oxidase
      catalytic subunits, was found to be prominently expressed in insulin-sensitive
      cells. By various molecular approaches, Nox4 was shown to mediate insulin
      stimulated H2O2 generation and impact the insulin signaling cascade.
      Overexpression of Nox4 also significantly reversed the inhibition of insulin
      stimulated receptor tyrosine phosphorylation by PTP1B, a widely expressed PTPase
      implicated in the negative regulation of insulin signaling, by inhibiting its
      catalytic activity. These recent studies have provided insight into Nox4 as a
      novel molecular link between insulin-stimulated reactive oxygen species and
      mechanisms involved in their modulation of insulin signal transduction.

PMID- 15998259
TI  - The molecular basis for oxidative stress-induced insulin resistance.
AB  - Reactive oxygen and nitrogen molecules have been typically viewed as the toxic by
      products of metabolism. However, accumulating evidence has revealed that reactive
      species, including hydrogen peroxide, serve as signaling molecules that are
      involved in the regulation of cellular function. The chronic and/or increased
      production of these reactive molecules or a reduced capacity for their
      elimination, termed oxidative stress, can lead to abnormal changes in
      intracellular signaling and result in chronic inflammation and insulin
      resistance. Inflammation and oxidative stress have been linked to insulin
      resistance in vivo. Recent studies have found that this association is not
      restricted to insulin resistance in type 2 diabetes, but is also evident in
      obese, nondiabetic individuals, and in those patients with the metabolic
      syndrome. An increased concentration of reactive molecules triggers the
      activation of serine/threonine kinase cascades such as c-Jun N-terminal kinase,
      nuclear factor-kappaB, and others that in turn phosphorylate multiple targets,
      including the insulin receptor and the insulin receptor substrate (IRS) proteins.
      Increased serine phosphorylation of IRS reduces its ability to undergo tyrosine
      phosphorylation and may accelerate the degradation of IRS-1, offering an
      attractive explanation for the molecular basis of oxidative stress-induced
      insulin resistance. Consistent with this idea, studies with antioxidants such as
      vitamin E, alpha-lipoic acid, and N-acetylcysteine indicate a beneficial impact
      on insulin sensitivity, and offer the possibility for new treatment approaches
      for insulin resistance.

PMID- 15998260
TI  - The role of reactive oxygen species in insulin signaling in the vasculature.
AB  - Although there is an abundance of evidence suggesting that insulin resistance
      plays a significant role in the vasculature, the precise mechanistic role
      involved still remains unclear. In this review, we discuss the current background
      of insulin resistance in the context of insulin signaling and action in the
      vasculature. Also, studies suggest that insulin resistance, diabetes, and
      cardiovascular disease all share a common involvement with oxidative stress.
      Recently, we reported that lysophosphatidylcholine, a major bioactive product of
      oxidized low-density lipoprotein, and angiotensin II, a vasoactive hormone and a
      potent inducer of reactive oxygen species (ROS), negatively regulate insulin
      signaling in vascular smooth muscle cells (VSMCs). In endothelial cells, insulin
      stimulates the release of nitric oxide, which results in VSMC relaxation and
      inhibition of atherosclerosis. Other data suggest that angiotensin II inhibits
      the vasodilator effects of insulin through insulin receptor substrate-1
      phosphorylation at Ser312 and Ser616. Moreover, ROS impair insulin-induced
      vasorelaxation by neutralizing nitric oxide to form peroxynitrite. Thus, evidence
      is growing to enable us to better understand mechanistically the relationship
      between insulin/insulin resistance and ROS in the vasculature, and the impact
      they have on cardiovascular disease.

PMID- 15998261
TI  - Redox modulation of insulin signaling and endothelial function.
AB  - Reactive oxygen and nitrogen species (ROS and RNS) recently emerged as critical
      signaling molecules in cardiovascular research. Several studies over the past
      decade have shown that physiological effects of vasoactive factors are mediated
      by these reactive species and, conversely, that altered redox mechanisms are
      implicated in the occurrence of metabolic and cardiovascular diseases. Oxidant
      stress occurs when ROS and/or RNS production exceeds the cell natural antioxidant
      systems, and pathological events ensue. Cardiovascular risk factors are
      associated with an imbalance of the redox equilibrium toward oxidative stress,
      leading to endothelial activation and proinflammatory processes implicated in
      atherogenesis and metabolic disorders. Recent studies indicate that insulin and
      insulin-sensitizing drugs activate antiinflammatory pathways that may limit
      oxidant stress in insulin target tissues. The main goal of this brief review is
      to discuss recent progress in the field of cellular redox signaling as it
      pertains to insulin modulation of vascular endothelial function in cardiovascular
      diseases.

PMID- 15998262
TI  - Oxidative enhancement of insulin receptor signaling: experimental findings and
      clinical implications.
AB  - Signaling through the insulin receptor and several other receptor tyrosine
      kinases is subject to redox regulation. Prolonged exposure to hydrogen peroxide
      impairs the action of insulin, and may account to some extent for the decreased
      insulin responsiveness in hyperglycemic diabetic patients. However, insulin
      receptor kinase (IRK) autophosphorylation and/or kinase activity were found to be
      markedly enhanced by a more limited exposure to hydrogen peroxide or by an
      oxidative shift in the thiol/disulfide redox status. Oxidative enhancement of IRK
      function may be mediated by two different mechanisms with similar effects, i.e.,
      by direct oxidative activation of IRK activity or by oxidative inactivation of a
      protein tyrosine phosphatase, which otherwise down-regulates IRK-mediated
      signaling. As both mechanisms enhance IRK activity in the absence of insulin,
      there is a strong possibility that the background IRK activity in the
      postabsorptive period may be abnormally increased in certain oxidative conditions
      and thereby disturb the metabolism of glucose and other energy substrates. This
      remains to be tested. In line with the oxidative enhancement of IRK activity,
      clinical studies have shown that treatment with a thiol-containing antioxidant
      increases the postabsorptive glucose and/or insulin concentrations (i.e., the
      HOMA-R index) at least under certain conditions. This effect may have therapeutic
      implications.

PMID- 15998263
TI  - Sensitivity of protein tyrosine phosphatase activity to the redox environment,
      cytochrome C, and microperoxidase.
AB  - Protein tyrosine phosphatase activity depends on a catalytic thiolate group on an
      acidic cysteine residue that is sensitive to reactive oxygen species.
      Representative of this family of enzymes is protein tyrosine phosphatase 1B
      (PTP1B), a major target for type 2 diabetes therapy. PTP1B is sensitive to
      hydrogen peroxide (H2O2) in vitro and in cells. It is also sensitive to
      glutathionylation by glutathione disulfide (GSSG). The sensitivity of PTP1B to
      the redox state of its environment was partially characterized in vitro by
      examination of phosphatase activity in the presence of various concentrations of
      glutathione (GSH) and GSSG. Enzyme sensitivity to glutathionylation was dependent
      on the amount of available thiol groups and increased as GSH concentration was
      increased. The half-inhibitory concentration for H2O2 was much less than that of
      GSSG in the presence of low concentrations of GSH, indicating that reaction with
      H2O2 is much more likely than is glutathionylation by GSSG. PTP1B and a related
      oxidant-sensitive phosphatase, PTEN, were also sensitive to the lipid
      peroxidation by-product 4-hydroxynonenal. Furthermore, PTP1B was inhibited by
      cytochrome c and microperoxidase. Taken together, these data suggest that not
      only H2O2, but also a variety of redox-active metabolites and hemes can
      oxidatively inactivate PTPs with potentially profound implications for signal
      transduction.

PMID- 15998266
TI  - A study into the plaque-inhibitory activity of experimental toothpaste
      formulations containing antimicrobial agents.
AB  - BACKGROUND/AIMS: The use of specific antimicrobial agents in toothpastes may help
      reduce plaque and gingivitis. There would also appear to be some value in
      formulating products that contain combinations of such agents that may potentiate
      any activity present. The aims of this exploratory and pragmatic study were
      twofold: (1) Exploratory: to compare the effects on plaque re-growth of two zinc
      citrate/triclosan formulations, one of which contained bromochlorophene and hence
      demonstrate any additional beneficial effects produced by the addition of the
      phenol. (2) Pragmatic: to assess whether both pastes were significantly better
      than a benchmark control, proprietary fluoride toothpaste at inhibiting plaque
      formation. METHODS: Following an initial prophylaxis to remove all plaque and
      calculus, toothpaste slurry rinses were used over a 96 h period by 24 volunteers,
      while omitting all other oral hygiene procedures. After 24, 48 and 96 h, plaque
      was measured by plaque area and by plaque index. For comparative purposes, a
      conventional commercial fluoride toothpaste rinse was also used as a benchmark
      control in this triple cross-over double-blind study. RESULTS: With one
      exception, comparisons between the three pastes failed to show any significant
      differences in plaque accumulation at 96 h whether assessed by plaque index or
      area. At this time period, significantly more plaque was seen with the zinc
      citrate paste without bromochlorophene, compared with that of the control paste.
      CONCLUSIONS: The findings from this study failed to demonstrate a plaque
      inhibitory action from the two novel formulations beyond that of a conventional
      benchmark toothpaste, although overall levels of plaque formed by the volunteers,
      especially on the control paste were generally lower than in previous studies.
      Nevertheless, it remains to be determined whether the test formulations could
      exert a direct anti-inflammatory action against gingivitis by way of the
      triclosan delivery system. Neither test formulation was subsequently marketed.

PMID- 15998267
TI  - Effectiveness of periodontal therapy on the severity of cyclosporin A-induced
      gingival overgrowth.
AB  - AIM: The purpose of the present study was to evaluate the clinical effects of
      aetiological periodontal treatment in a group of transplant patients medicated
      with cyclosporin A (CsA) who exhibited severe gingival overgrowth. MATERIALS AND
      METHODS: Twenty-one patients received oral hygiene instructions, supra- and
      subgingival scaling and periodontal maintenance therapy and were monitored for 12
      months. Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS),
      periodontal probing depth and degree of gingival overgrowth (Seymour index GO)
      were recorded at baseline, 6 and 12 months after treatment. RESULTS: Statistical
      evaluation revealed that all clinical variables significantly decreased compared
      with baseline. At baseline 18 out of 21 treated patients (85.71%) exhibited
      clinically significant overgrowth. Initial GO score of 2.38+/-1.92 in the
      anterior sextants and of 1.29+/-1.59 in the posterior segments were reduced to
      0.56+/-0.83 and to 0.45+/-0.84 at 12 months (p<0.001). A difference of 1.82 and
      0.84 in the severity of treated GO was accompanied by a 42% and 34% decrease in
      FMPS and FMBS, respectively. CONCLUSIONS: Aetiological periodontal treatment and
      regular maintenance therapy were effective in resolving the inflammation and in
      eliminating the need for surgical treatment in patients receiving CsA.

PMID- 15998268
TI  - Full-mouth ultrasonic debridement versus quadrant scaling and root planing as an
      initial approach in the treatment of chronic periodontitis.
AB  - AIM: To evaluate the clinical efficacy of (i) a single session of "full-mouth
      ultrasonic debridement" (Fm-UD) as an initial periodontal treatment approach and
      (ii) re-instrumentation of periodontal pockets not properly responding to initial
      subgingival instrumentation. METHODS: Forty-one patients, having on the average
      35 periodontal sites with probing pocket depth (PPD) > or =5 mm, were randomly
      assigned to two different treatment protocols following stratification for
      smoking: a single session of full-mouth subgingival instrumentation using a
      piezoceramic ultrasonic device (EMS PiezonMaster 400, A+PerioSlim tips) with
      water coolant (Fm-UD) or quadrant scaling/root planing (Q-SRP) with hand
      instruments . At 3 months, all sites with remaining PPD> or =5 mm were subjected
      to repeated debridement with either the ultrasonic device or hand instruments.
      Plaque, PPD, relative attachment level (RAL) and bleeding following pocket
      probing (BoP) were assessed at baseline, 3 and 6 months. Primary efficacy
      variables were percentage of "closed pockets" (PPD< or =4 mm), and changes in
      BoP, PPD and RAL. RESULTS: The percentage of "closed pockets" was 58% at 3 months
      for the Fm-UD approach and 66% for the Q-SRP approach (p>0.05). Both treatment
      groups showed a mean reduction in PPD of 1.8 mm, while the mean RAL gain amounted
      to 1.3 mm for Fm-UD and 1.2 mm for Q-SRP (p>0.05). The re-treatment at 3 months
      resulted in a further mean PPD reduction of 0.4 mm and RAL gain of 0.3 mm at 6
      months, independent of the use of ultrasonic or hand instruments. The efficiency
      of the initial treatment phase (time used for instrumentation/number of pockets
      closed) was significantly higher for the Fm-UD than the Q-SRP approach: 3.3
      versus 8.8 min. per closed pocket (p<0.01). The efficiency of the re-treatment
      session at 3 months was 11.5 min. for ultrasonic and 12.6 min. for hand
      instrumentation (p>0.05). CONCLUSION: The results demonstrated that a single
      session of Fm-UD is a justified initial treatment approach that offers tangible
      benefits for the chronic periodontitis patient.

PMID- 15998269
TI  - Prevalence of periodontal pathogens in Brazilians with aggressive or chronic
      periodontitis.
AB  - OBJECTIVES: Previous studies suggest differences between geographically and
      racially distinct populations in the prevalence of periodontopathic bacteria as
      well as greater periodontal destruction associated with infection by highly
      leucotoxic Actinobacillus actinomycetemcomitans. The present study examined these
      hypotheses in Brazilians with aggressive or chronic periodontitis. MATERIALS AND
      METHODS: Clinical, radiographical, and microbiological assessments were performed
      on 25 aggressive periodontitis and 178 chronic periodontitis patients including
      71 males and 132 females, 15-69 years of age. RESULTS: The prevalence of
      Porphyromonas gingivalis was similar to that of other South American populations.
      The prevalence of A. actinomycetemcomitans and its highly leucotoxic subgroup was
      higher in Brazilians. Highly leucotoxic A. actinomycetemcomitans was more
      prevalent in aggressive periodontitis (chi2=27.83) and positively associated with
      deep pockets (>6 mm, chi2=18.26) and young age (<29 years, chi2=18.68). Greater
      mean attachment loss was found in subjects with highly leucotoxic A.
      actinomycetemcomitans than in subjects with minimally leucotoxic (p=0.0029) or
      subjects not infected (p=0.0001). CONCLUSION: These data support the hypothesis
      of differences between populations in the prevalence of periodontopathic bacteria
      and of greater attachment loss in sites infected with highly leucotoxic A.
      actinomycetemcomitans. Detection of highly leucotoxic A. actinomycetemcomitans in
      children and adolescents may be a useful marker for aggressive periodontitis.

PMID- 15998270
TI  - Should quit smoking interventions be the first part of initial periodontal
      therapy?

PMID- 15998271
TI  - The effect of quitting smoking on chronic periodontitis.
AB  - OBJECTIVES: To evaluate longitudinally the effect of smoking cessation on
      clinical and radiographic outcomes following non-surgical treatment in smokers
      with chronic periodontitis. MATERIAL AND METHODS: Forty-nine smokers with chronic
      periodontitis who wished to quit smoking were recruited. Full-mouth probing
      depths, bleeding and plaque data were recorded at baseline, 3, 6 and 12 months.
      Clinical attachment levels were recorded at target sites and subtraction
      radiography was used to assess bone density changes. Patients received non
      surgical periodontal therapy during the first 3 months and supportive periodontal
      care over the remainder of the study. Smoking cessation counselling was provided
      according to individual need. RESULTS: After 12 months, of patients with complete
      data, 10 had continuously quit smoking (20% of the original population), 10
      continued smoking and six were oscillators (those patients who quit and then
      relapsed). There were no differences between the groups following treatment with
      respect to mean clinical or radiographic parameters. Analysis of probing depth
      reductions between baseline and month 12, however, and comparing quitters with
      the other two groups combined, demonstrated a significant difference in favour of
      quitters (p<0.05). Furthermore, quitters were significantly more likely to
      demonstrate probing depth reductions > or =2 and > or =3 mm than non-quitters and
      oscillators (p<0.05). CONCLUSION: Quitting smoking has an additional beneficial
      effect in reducing probing depths following non-surgical treatment over a 12
      month period.

PMID- 15998272
TI  - Gingival crevicular fluid EMAP-II, MIP-1alpha and MIP-1beta levels of patients
      with periodontal disease.
AB  - BACKGROUND: Periodontal diseases may differ, which could be attributed to the
      factors that might modify the host response to microbial pathogens. The aim of
      this study was to examine gingival crevicular fluid (GCF) levels of EMAP-II, MIP
      1alpha and MIP-1beta in patients with different periodontal diseases (EMAP-II,
      endothelial-monocyte activating polypeptide; MIP-1alpha, macrophage inflammatory
      protein-1alpha; MIP-1beta, macrophage inflammatory protein-1beta). METHODS:
      Eighty-two subjects were included in this study. GCF samples were collected from
      26 patients with generalized aggressive periodontitis (G-AgP), 26 patients with
      chronic periodontitis (CP), 15 with gingivitis and 15 periodontally healthy
      subjects. Clinical periodontal parameters were recorded. GCF EMAP-II, MIP-1alpha
      and MIP-1beta levels were quantified by enzyme immunoassay. RESULTS: GCF EMAP-II
      levels of G-AgP group were higher than those of gingivitis and healthy groups
      (p<0.008). G-AgP group showed a trend for higher GCF EMAP-II levels compared with
      CP group (p>0.008). G-AgP, CP, gingivitis and healthy groups had comparable GCF
      MIP-1alpha and MIP-1beta levels. CONCLUSIONS: Our results suggest that elevated
      GCF EMAP-II could contribute to the pathogenesis of G-AgP. Alternatively, EMAP-II
      reflects the extent of the inflammatory activity in the periodontal tissues. At
      this point, MIP-1alpha and MIP-1beta levels in GCF do not seem to play a
      discriminatory role in periodontitis. Our data document for the first time the
      essential role of EMAP-II in the pathogenesis of different periodontal diseases.

PMID- 15998273
TI  - Association between periodontitis and low birth weight: a case-control study.
AB  - OBJECTIVE: To verify a possible association between periodontitis and low-birth
      weight babies. MATERIAL AND METHODS: One hundred and fifty-one mothers were
      examined. The case group included 76 mothers (mean age 25.6 years), whose babies
      at birth weighed <2500 g and had a gestational age (GA) <37 weeks, while 75
      mothers (mean age 24.4 years), whose babies were born with a weight of >2500 g
      and with a GA>37 weeks, were the control group. Data from the mothers and the
      babies were collected from the Hospital registration records and during an
      interview with the mother. The periodontal examination included measurements of
      probing pocket depth (PPD) and clinical attachment loss (CAL) in six sites from
      all existing teeth, except for third molars. Mothers with periodontitis had at
      least four sites with PPD> or =4 and CAL> or =3 mm, while healthy mothers had
      PPD< or =3 mm and CAL< or =1 mm. RESULTS: The median number of sites with PPD> or
      =4 and CAL> or =3 mm was eight in the case group, and four in the control group.
      The significant associations with low birth weight (LBW) babies were
      periodontitis (odds ratio (OR)=3.48, 95% confidence interval (CI): 1.17; 10.36),
      arterial hypertension (OR=9.65, 95% CI: 2.22; 41.91), haemorrhage during
      pregnancy (OR=10.88, 95% CI: 1.95; 60.53), number of pre-natal examinations
      (OR=0.10, 95% CI: 0.02; 0.43) and genitourinary infection (OR=3.21, 95% CI: 1.25;
      8.20). CONCLUSION: Periodontitis was considered a risk indicator for LBW in this
      sample, similar to other risk factors already recognized by obstetricians.

PMID- 15998274
TI  - Antimicrobial profiles of periodontal pathogens and systemic antimicrobial
      therapy.

PMID- 15998275
TI  - Antimicrobial profiles of periodontal pathogens isolated from periodontitis
      patients in The Netherlands and Spain.
AB  - BACKGROUND AND AIM: Antimicrobial resistance of periodontal pathogens towards
      currently used antibiotics in periodontics has been investigated in a previous
      study. Microbial resistance in the periodontal microflora was more frequently
      observed in Spanish patients in comparison with Dutch patients. The aim of the
      present study was to compare antimicrobial susceptibility profiles of five
      periodontal bacteria isolated from periodontitis patients in Spain and in The
      Netherlands. MATERIAL AND METHODS: Subgingival plaque samples from adult patients
      with periodontitis were collected and cultured on selective and non-selective
      plates. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia, Fusobacterium nucleatum and Micromonas micros were
      isolated and used for minimal inhibitory concentration tests using the
      Epsilometer (E-test) technique. Eight different antibiotics were tested on all
      bacterial isolates. MIC50 and MIC90 values for each antibiotic and each species
      were determined and the percentage of resistant strains was calculated. RESULTS:
      Significantly higher MIC values were noted in Spanish strains of F. nucleatum for
      penicillin, ciprofloxacin, of P. intermedia for penicillin, amoxicillin and
      tetracycline, of M. micros for tetracycline, amoxicillin and azithromycin, and of
      P. gingivalis for tetracycline and ciprofloxacin. Based on breakpoint
      concentrations, a higher number of resistant strains in Spain were found in F.
      nucleatum for penicillin, amoxicillin and metronidazole, in Prevotella intermedia
      for tetracycline and amoxicillin, and in A. actinomycetemcomitans for amoxicillin
      and azithromycin. Resistance of P. gingivalis strains was not observed for any of
      the antibiotics tested both in Spain and The Netherlands. CONCLUSIONS:
      Differences exist in the susceptibility profiles of periodontal pathogens
      isolated from periodontitis patients in Spain and in The Netherlands. This
      implicates that antibiotic susceptibility testing is necessary to determine
      efficacy of antimicrobial agents. Also, clinical studies with antibiotics should
      take these differences into account. The information from the present study
      indicates that it may not be possible to develop uniform protocols for usage of
      antibiotics in the treatment of severe periodontitis in the European Union.

PMID- 15998276
TI  - Short-term anti-plaque effect of two chlorhexidine varnishes.
AB  - BACKGROUND: Chlorhexidine (CHX) varnishes have been mainly used for the
      prevention of caries in high-risk populations. Reports regarding their anti
      plaque effect on a clinical level are limited to non-existing as opposed to their
      microbiological impact on plaque formation. AIM: The aim of this preliminary
      investigation was to evaluate the anti-plaque effect of two CHX varnishes applied
      on sound enamel in relation to a positive control, a negative control and to one
      another. METHODS: Sixteen healthy subjects volunteered for this randomized
      controlled, single-blind, four-treatment-four-period crossover-designed clinical
      trial. A 3-day plaque re-growth model was used to determine de novo plaque
      accumulation following CHX rinsing, Cervitec application, EC40 application and no
      therapy. The amount of plaque was measured using the Quigley and Hein plaque
      index and "automatic image analysis" (AIA). RESULTS AND CONCLUSIONS: Varnish
      treatment resulted in significantly higher plaque levels than CHX rinsing
      irrespective of the varnish that was used (p< or =0.002), implying that the
      latter is likely to remain the gold standard as an anti-plaque agent. However,
      highly significant differences were also found in favour of both varnish systems
      when compared with no therapy (p<0.001), which indicates that varnish treatment
      is an effective means of inhibiting plaque formation in a short time span.
      Cervitec exhibited slightly, yet significantly, higher plaque levels in
      comparison with EC40 as determined by AIA (p=0.006). Large-scale trials with a
      longer observation period are necessary to substantiate these results.

PMID- 15998277
TI  - Periodontal wound healing following GTR therapy of dehiscence-type defects in the
      monkey: short-, medium- and long-term healing.
AB  - OBJECTIVE: To describe periodontal wound healing in dehiscence-type defects
      following guided tissue re-generation (GTR) therapy. METHODS: Ten adult Macaca
      fascicularis monkeys were used. Buccal dehiscence-type defects were created at
      the maxillary second pre-molars and second molars. After 3 months, GTR surgery
      was performed. The animals were euthanized at 6 weeks, 6 months and 2 years after
      surgery. Block biopsies were harvested, and prepared for histological analysis.
      RESULTS: A new attachment apparatus was structured already after 6 weeks of
      healing. A 10-20 microm thin layer of acellular extrinsic fibre cementum (AEFC)
      had formed along the instrumented root surface. At 6 months, the thickness of the
      supracrestal cementum was comparable with that at 6 weeks, while the thickness of
      the subcrestal cementum had increased to 40-60 microm. In this zone, the cementum
      consisted of an inner layer of AEFC attached to the circum-pulpal dentin and an
      outer layer of cellular mixed fibre cementum (CMFC). The numerical extrinsic
      fibre density was twice that at 6 weeks. At 2 years, the periodontal tissues
      resembled the pristine periodontium. CONCLUSION: Periodontal healing following
      GTR therapy of recession-type defects will result in a restitutio ad integrum,
      i.e. healing by re-generation. A continuous maturation process occurs over at
      least 2 years.

PMID- 15998278
TI  - Effect of non-surgical periodontal treatment with or without doxycycline on the
      periodontium of type 1 diabetic patients.
AB  - AIM: The present investigation was performed to study how type 1 diabetics
      responded to non-surgical periodontal treatment with and without adjunctive
      doxycycline. METHOD: Sixty diabetic type 1 patients (mean age 35.3+/-9 years)
      with moderate-to-severe periodontal disease were selected and divided into two
      groups of 30 patients each. Both groups were sex and age matched and had similar
      amounts of periodontal destruction. Plaque index (PI), bleeding on probing (BOP),
      probing depth (PD) and clinical attachment levels (CAL) were recorded. Group 1
      (30 patients) was treated with oral hygiene instruction, scaling and root
      planing, chlorhexidine rinses twice a day and doxycycline (100 mg/day for 15
      days). Group 2 (30 patients) had the same treatment but without doxycycline.
      After 12 weeks their periodontal condition was reevaluated. RESULTS: After
      treatment, both groups had a significant improvement in all periodontal
      parameters, since PI, BOP, probing pocket depth (PPD) and CAL were significantly
      reduced. However, the reduction in PD in pockets > or =6 mm and in BOP were more
      evident when doxycycline was used (group 1). Differences between groups for these
      parameters were statistically significant (p=0.03). CONCLUSION: Although both
      periodontal treatment regimens are effective in type 1 diabetics, the use of
      doxycycline as an adjunct, provided more significant results when good plaque
      control was achieved.

PMID- 15998279
TI  - Haemangiopericytoma of the maxillary gingiva: report of a case.
AB  - AIM: Haemangiopericytoma (HPC) represents approximately 3% of all tumours in the
      head and neck. This tumour is a soft tissue tumour derived from mesenchymal cells
      with pericytic differentiation. We present the clinicopathological findings of a
      case. MATERIALS AND METHODS: A 69-year-old man was referred to our Department for
      a mass located on the right pre-molar maxillary gingiva; this mass caused
      problems during chewing, but was otherwise asymptomatic. RESULTS: Clinical
      examination revealed a nodular, pink lesion, 3.5 cm in diameter, which was lined
      with normal mucosa. The lesion was mobile in relation to the deep and superficial
      tissues. Microscopic analysis of the neoplasm showed a vascular rich pattern,
      constituted by vessels covered with flat endothelium and surrounded by abundant
      spindly cells. On the basis of these histological and immunohistochemical
      findings, the final diagnosis was HPC. CONCLUSIONS: HPC is an uncommon vascular
      tumour for which the biological behaviour is difficult to predict. In our
      patient, no recurrences or distant metastases were present at a 4 years follow
      up.

PMID- 15998280
TI  - Amyloid beta peptide 1-40 enhances the action of Toll-like receptor-2 and -4
      agonists but antagonizes Toll-like receptor-9-induced inflammation in primary
      mouse microglial cell cultures.
AB  - The interaction of endogenous and exogenous stimulators of innate immunity was
      examined in primary cultures of mouse microglial cells and macrophages after
      application of defined Toll-like receptor (TLR) agonists [lipopolysaccharide
      (LPS) (TLR4), the synthetic lipopeptide Pam3Cys-Ser-Lys4 (Pam3Cys) (TLR2) and
      single-stranded unmethylated CpG-DNA (CpG) (TLR9)] alone and in combination with
      amyloid beta peptide (Abeta) 1-40. Abeta1-40 stimulated microglial cells and
      macrophages primed by interferon-gamma in a dose-dependent manner. Co
      administration of Abeta1-40 with LPS or Pam3Cys led to an additive release of
      nitric oxide (NO) and tumour necrosis factor alpha (TNF-alpha). This may be one
      reason for the clinical deterioration frequently observed in patients with
      Alzheimer's disease during infections. In contrast, co-application of Abeta1-40
      with CpG led to a substantial decrease of NO and TNF-alpha release compared with
      stimulation with CpG alone. Abeta1-40 and CpG did not co-localize within the same
      subcellular compartment, making a direct physicochemical interaction as the cause
      of the observed antagonism very unlikely. This suggests that not all TLR agonists
      enhance the stimulatory effect of A beta on innate immunity.

PMID- 15998282
TI  - Cellular localization and subcellular distribution of Unc-33-like protein 6, a
      brain-specific protein of the collapsin response mediator protein family that
      interacts with the neuronal glycine transporter 2.
AB  - Unc-33-like protein (Ulip)6, a brain-specific phosphoprotein of the
      Ulip/collapsin response mediator protein family, was originally identified in our
      laboratory by yeast two-hybrid screening using the cytoplasmic N-terminal domain
      of the neuronal glycine transporter, glycine transporter (GlyT) 2, as a bait.
      Here, the interaction of Ulip6 with the N-terminal domain of GlyT2 was found to
      be specific for this member of the Ulip/collapsin response mediator protein
      family and to involve amino acids 135-184 of GlyT2. In pull-down assays and
      coimmunoprecipitation experiments with rat spinal cord extract, the presence of
      phosphatase inhibitors significantly enhanced binding of Ulip6 to GlyT2.
      Subcellular fractionation of spinal cord and retina homogenates at different
      developmental stages showed Ulip6 immunoreactivity to be associated with light
      vesicles that were distinct from GlyT2-containing and synaptic vesicles.
      Immunocytochemistry revealed punctate Ulip6 immunoreactivity in both somatic
      regions and processes of cultured spinal neurones; no colocalization with GlyT2
      or other synaptic marker proteins was found. In retina, which expresses only
      GlyT1 but not GlyT2, Ulip6 was detected in the inner plexiform layer and along
      the somata and processes of selected bipolar, amacrine and ganglion cells. Our
      data support a model in which Ulip6 transiently interacts with GlyT2 in a
      phosphorylation-dependent manner.

PMID- 15998281
TI  - NADPH oxidase is required for NMDA receptor-dependent activation of ERK in
      hippocampal area CA1.
AB  - Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor activation
      results in production of reactive oxygen species (ROS) and activation of
      extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition,
      application of ROS to hippocampal slices has been shown to result in activation
      of ERK in area CA1. To determine whether these events were linked causally, we
      investigated whether ROS are required for NMDA receptor-dependent activation of
      ERK. In agreement with previous studies, we found that treatment of hippocampal
      slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor
      dependent activation of ERK was either blocked or attenuated by a number of
      antioxidants, including the general antioxidant N-acetyl-L-cysteine (L-NAC), the
      superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable
      SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen
      peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA
      receptor-dependent activation of ERK also was blocked by the NADPH oxidase
      inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked
      p47(phox), one of the required protein components of NADPH oxidase. Taken
      together, our results suggest that ROS production, especially superoxide
      production via NADPH oxidase, is required for NMDA receptor-dependent activation
      of ERK in hippocampal area CA1.

PMID- 15998283
TI  - Amplification of depolarization-induced and ryanodine-sensitive cytosolic Ca2+
      elevation by synthetic carbocyclic analogs of cyclic ADP-ribose and their
      antagonistic effects in NG108-15 neuronal cells.
AB  - We synthesized analogs modified in the ribose unit (ribose linked to N1 of
      adenine) of cyclic ADP-ribose (cADPR), a Ca2+-mobilizing second messenger. The
      biological activities of these analogs were determined in NG108-15 neuroblastoma
      x glioma hybrid cells that were pre-loaded with fura-2 acetoxymethylester and
      subjected to whole-cell patch-clamp. Application of the hydrolysis-resistant
      cyclic ADP-carbocyclic-ribose (cADPcR) through patch pipettes potentiated
      elevation of the cytoplasmic free Ca2+ concentration ([Ca2+]i) at the depolarized
      membrane potential. The increase in [Ca2+]i evoked upon sustained membrane
      depolarization was significantly larger in cADPcR-infused cells than in non
      infused cells and its degree was equivalent to or significantly greater than that
      induced by cADPR or beta-NAD+. 8-Chloro-cADPcR and two inosine congeners (cyclic
      IDP-carbocyclic-ribose and 8-bromo-cyclic IDP-carbocyclic-ribose) did not induce
      effects similar to those of cADPcR or cADPR. Instead, 8-chloro-cADPcR together
      with cADPR or cADPcR caused inhibition of the depolarization-induced [Ca2+]i
      increase as compared with either cADPR or cADPcR alone. These results
      demonstrated that our cADPR analogs have agonistic or antagonistic effects on the
      depolarization-induced [Ca2+]i increase and suggested the presence of functional
      reciprocal coupling between ryanodine receptors and voltage-activated Ca2+
      channels via cADPR in mammalian neuronal cells.

PMID- 15998284
TI  - Histone methylation at gene promoters is associated with developmental regulation
      and region-specific expression of ionotropic and metabotropic glutamate receptors
      in human brain.
AB  - Glutamatergic signaling is regulated, in part, through differential expression of
      NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors.
      In human brain, region-specific expression patterns of glutamate receptor genes
      are maintained over the course of decades, suggesting a role for molecular
      mechanisms involved in long-term regulation of transcription, including
      methylation of lysine residues at histone N-terminal tails. Using a native
      chromatin immunoprecipitation assay, we studied histone methylation marks at
      proximal promoters of 16 ionotropic and metabotropic glutamate receptor genes
      (GRIN1,2A-D; GRIA1,3,4; GRIK2,4,5; GRM1,3,4,6,7 ) in cerebellar cortex collected
      across a wide age range from midgestation to 90 years old. Levels of di- and
      trimethylated histone H3-lysine 4, which are associated with open chromatin and
      transcription, showed significant differences between promoters and a robust
      correlation with corresponding mRNA levels in immature and mature cerebellar
      cortex. In contrast, levels of trimethylated H3-lysine 27 and H4-lysine 20, two
      histone modifications defining silenced or condensed chromatin, did not correlate
      with transcription but were up-regulated overall in adult cerebellum.
      Furthermore, differential gene expression patterns in prefrontal and cerebellar
      cortex were reflected by similar differences in H3-lysine 4 methylation at
      promoters. Together, these findings suggest that histone lysine methylation at
      gene promoters is involved in developmental regulation and maintenance of region
      specific expression patterns of ionotropic and metabotropic glutamate receptors.
      The association of a specific epigenetic mark, H3-(methyl)-lysine 4, with the
      molecular architecture of glutamatergic signaling in human brain has potential
      implications for schizophrenia and other disorders with altered glutamate
      receptor function.

PMID- 15998285
TI  - Comparative evaluation of positron emission tomography radiotracers for imaging
      the norepinephrine transporter: (S,S) and (R,R) enantiomers of reboxetine analogs
      ([11C]methylreboxetine, 3-Cl-[11C]methylreboxetine and [18F]fluororeboxetine),
      (R)-[11C]nisoxetine, [11C]oxaprotiline and [11C]lortalamine.
AB  - We have synthesized and evaluated several new ligands for imaging the
      norepinephrine transporter (NET) system in baboons with positron emission
      tomography (PET). Ligands possessing high brain penetration, high affinity and
      selectivity, appropriate lipophilicity (log P = 1.0-3.5), high plasma free
      fraction and reasonable stability in plasma were selected for further studies.
      Based on our characterization studies in baboons, including 11C-labeled (R)
      nisoxetine (Nis), oxaprotiline (Oxap), lortalamine (Lort) and new analogs of
      methylreboxetine (MRB), in conjunction with our earlier evaluation of 11C and 18F
      derivatives of reboxetine, MRB and their individual (R,R) and (S,S) enantiomers,
      we have identified the superiority of (S,S)-[11C]MRB and the suitability of MRB
      analogs [(S,S)-[11C]MRB > (S,S)-[11C]3-Cl-MRB > (S,S)-[18F]fluororeboxetine] as
      potential NET ligands for PET. In contrast, Nis, Oxap and Lort displayed high
      uptake in striatum (higher than in thalamus). The use of these ligands is further
      limited by high non-specific binding and relatively low specific signal, as is
      characteristic of many earlier NET ligands. Thus, to our knowledge (S,S)-[11C]MRB
      remains by far the most promising NET ligand for PET studies.

PMID- 15998286
TI  - A triple mutation in the second transmembrane domain of mouse dopamine
      transporter markedly decreases sensitivity to cocaine and methylphenidate.
AB  - Previously, we reported that Phe105 in transmembrane domain 2 of the mouse
      dopamine transporter (DAT) is crucial for high-affinity cocaine binding. In the
      current study, we investigated whether other residues surrounding Phe105 also
      affect the potency of cocaine inhibition. After three rounds of sequential random
      mutagenesis at these residues, we found a triple mutant (L104V, F105C and A109V)
      of mouse DAT that retained over 50% uptake activity and was 69-fold less
      sensitive to cocaine inhibition when compared with the wild-type mouse DAT. The
      triple mutation also resulted in a 47-fold decrease in sensitivity to
      methylphenidate inhibition, suggesting that the binding sites for cocaine and
      methylphenidate may overlap. In contrast, the inhibition of dopamine uptake by
      amphetamine or methamphetamine was not significantly changed by the mutations,
      suggesting that the binding sites for the amphetamines differ from those for
      cocaine and methylphenidate. Such functional but cocaine-insensitive DAT mutants
      can be used to generate a knock-in mouse line to study the role of DAT in cocaine
      addiction.

PMID- 15998287
TI  - Selectively increasing inducible heat shock protein 70 via TAT-protein
      transduction protects neurons from nitrosative stress and excitotoxicity.
AB  - Induction of heat shock protein 70 (Hsp70) via sublethal stress protects neurons
      from subsequent lethal injuries. Here we show that specific and efficient
      intracellular transduction of Hsp70 can be achieved utilizing an 11 amino acid
      leading sequence from human immunodeficiency virus (TAT-Hsp70) in primary
      neuronal cultures. Western blot and immunohistochemistry demonstrated
      intracellular accumulation of Hsp70 in insoluble protein fractions and
      mitochondrial compartments. We then examined the effects of Hsp70 overexpression
      using TAT-Hsp70 in models of nitrosative and excitotoxic neuronal death in vitro.
      Neurons were pre-incubated with 300 nM TAT-Hsp 70 overnight, then exposed to
      either peroxynitrite (ONOO-) or glutamate. TAT-Hsp70 maintained cellular
      respiration, inhibited extracellular lactate dehydrogenase release, and/or
      reduced cell death assessed by flow cytometry vs. vehicle, wild-type Hsp70, and
      TAT-beta-galactosidase controls. Hsp70 transduction using a TAT fusion protein is
      an effective method to selectively increase Hsp70 in neurons and is sufficient to
      provide neuroprotection from nitrosative stress and excitotoxicity. Further study
      is needed to confirm whether TAT-Hsp70 is protective in in vivo models of brain
      injury.

PMID- 15998288
TI  - The p38 mitogen-activated protein kinase pathway negatively regulates Ca2+
      activated K+ channel trafficking in developing parasympathetic neurons.
AB  - The trafficking of large-conductance Ca2+-activated K+ channels (K(Ca)) in chick
      ciliary ganglion neurons is regulated by growth factors. Here we show that a
      canonical p38 cascade inhibits K(Ca) trafficking in ciliary ganglion neurons. Two
      different p38 inhibitors (SB202190 or SB203580) or over-expression of dominant
      negative forms of several components of the p38 cascade increased K(Ca) in
      ciliary neurons. Inhibition of protein synthesis or Golgi processing had no
      effect on this phenomenon, suggesting that p38 is acting at a distal step of the
      trafficking pathway. Depolymerization of filamentous actin (F-actin) increased
      functional expression of K(Ca), whereas stabilization of F-actin inhibited the
      effect of SB202190 on K(Ca) trafficking. SB202190 also caused an immunochemically
      detectable increase in K(Ca) on the plasma membrane. Inhibition of p38 decreased
      the extent of cortical F-actin in ciliary neurons. Macroscopic K(Ca) is
      suppressed by transforming growth factor (TGF) beta3. Application of TGFbeta3
      increased the phosphorylation of p38 in ciliary neurons and increased cortical F
      actin. Thus, the p38 signaling cascade endogenously suppresses development of
      functional K(Ca), in part by stabilizing an F-actin barrier that prevents plasma
      membrane insertion of functional channel complexes. This cascade also appears to
      mediate inhibitory effects of TGFbeta3 on the expression of K(Ca).

PMID- 15998289
TI  - Proteomic identification of differentially expressed proteins in the aging murine
      olfactory system and transcriptional analysis of the associated genes.
AB  - Decline in olfactory ability has been associated with aging as well as
      neurodegenerative disorders. The aim of this study was to gain fundamental
      insight into molecular events associated with the aging olfactory system. We
      report a comparative proteomic analysis of the olfactory epithelium (OE) and
      olfactory bulb (OB) of old (80-week old) and young (6-week old) mice with further
      analysis of age-related differences in differentially expressed proteins at the
      mRNA level using real-time RT-PCR. Nine proteins in the OE and 20 in the OB were
      differentially expressed in old and young mice; of these, aldolase 1, peptidyl
      prolyl isomerase A, mitochondrial aconitase 2, mitochondrial aldehyde
      dehydrogenase 2 and albumin 1 were identified in the OE; and ATP synthase isoform
      1, enolase 1, ferritin heavy chain, malate dehydrogenase 1, tropomyosin alpha 3
      chain and dynamin 1 were identified in the OB. At the transcriptional level,
      aconitase 2 in the OE and ferritin heavy chain 1 in the OB were differentially
      expressed with aging, in concordance with the proteomic data. Our results
      demonstrate an altered proteomic profile of the aged murine olfactory system. The
      identified proteins fall into three broadly defined functional categories: (i)
      metabolism, (ii) transport/motility and (iii) stress response. Our
      transcriptional analysis provides insight into possible mechanisms by which
      protein expression may be regulated in the OE and OB. The results are discussed
      in relation to the decrement in olfactory sensitivity with aging.

PMID- 15998290
TI  - Peripheral injection of lipopolysaccharide enhances expression of inflammatory
      cytokines in murine locus coeruleus: possible role of increased norepinephrine
      turnover.
AB  - Cytokines and catecholamines are known to constitute a significant portion of the
      regulatory neuroimmune networks involved in maintaining homeostasis in the
      central nervous system (CNS). Although we have already reported an increase in
      norepinephrine (NE) turnover within the locus coeruleus (LC) at 2 and 4 h after
      the intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), the implication
      of this increase remains unclear. In view of evidence that norepinephrine (NE)
      acts in an anti-inflammatory manner by way of negatively regulating pro
      inflammatory cytokine expression, we examined the inflammatory cytokine
      expression levels in the LC of C3H/HeN mice (male, 8 weeks old) after an i.p. LPS
      injection. The mRNA expression levels of the genes encoding IL-1beta and TNF
      alpha within the LC increased during the first 2 h, and showed two peaks, the
      first at 4 h and the second lesser one at 15 h after the LPS injection.
      Microglia, which are one of the major cell types that produce pro-inflammatory
      cytokines in the CNS, were isolated from mouse neonate brains in order to clarify
      more precisely the relationship between the changes in NE content and the up
      regulation of inflammatory cytokines in the LC. Simultaneous incubation of
      microglia with LPS and NE enhanced the expression of IL-1beta at both mRNA and
      protein levels, but reduced the mRNA and protein levels of TNF-alpha. These data
      support the hypothesis that NE negatively regulates the expression of pro
      inflammatory cytokine expression, at least in the case of TNF-alpha, which action
      could contribute to the observed anti-inflammatory properties of NE. This report,
      based on the results of both in vivo and in vitro experiments, is the first to
      suggest a relationship between NE content and cytokine expression levels in the
      CNS.

PMID- 15998291
TI  - Acute up-regulation of glutamate uptake mediated by mGluR5a in reactive
      astrocytes.
AB  - Excitatory transmission in the CNS necessitates the existence of dynamic controls
      of the glutamate uptake achieved by astrocytes, both in physiological conditions
      and under pathological circumstances characterized by gliosis. In this context,
      this study was aimed at evaluating the involvement of group I metabotropic
      glutamate receptors (mGluR) in the regulation of glutamate transport in a model
      of rat astrocytes undergoing in vitro activation using a cocktail of growth
      factors (G5 supplement). The vast majority of the cells were found to take up
      aspartate, mainly through the glutamate/aspartate transporter (GLAST), and at
      least 60% expressed functional mGluR5a. When exposed for 15 s to the selective
      group I mGluR agonist (S)-3,5-dihydroxyphenylglycine, reactive astrocytes showed
      a significant increase in their capacity to take up aspartate. This effect was
      confirmed at the single-cell level, since activation of mGluRs significantly
      increased the initial slope of aspartate-dependent Na+ entry associated with the
      activity of glutamate transporters. This up-regulation was inhibited by an
      antagonist of mGluR5 and, more importantly, was sensitive to a specific glutamate
      transporter 1 (GLT-1) blocker. The acute influence of mGluR5 on aspartate uptake
      was phospholipase C- and protein kinase C-dependent, and was mimicked by phorbol
      esters. We conclude that mGluR5a contributes to a dynamic control of GLT-1
      function in activated astrocytes, acting as a glial sensor of the extracellular
      glutamate concentration in order to acutely regulate the excitatory transmission.

PMID- 15998292
TI  - Retrovirally transduced NCAM140 facilitates neuronal fate choice of hippocampal
      progenitor cells.
AB  - Neural cell adhesion molecule (NCAM) influences proliferation and differentiation
      of neuronal cells. However, only a little is known about the downstream effects
      of NCAM signalling, such as alterations in gene transcription, which are
      associated with cell fate choice. To examine whether NCAM plays a role in cell
      fate choice during hippocampal neurogenesis, we performed a gain-of-function
      study, using a retroviral vector which contained full-length NCAM140 cDNA and the
      marker gene EGFP, and found that NCAM140 promoted neurogenesis by activating
      proneural transcription activators with concurrent inhibition of gliogenesis. The
      enhanced transcript levels of proneural transcription factors in NCAM140
      transduced cells were down-regulated by treatment of the cells with mitogen
      activated protein kinase kinase (MEK) inhibitor PD098059. Overall, these findings
      suggest that NCAM140 may facilitate hippocampal neurogenesis via regulation of
      proneurogenic transcription factors in an extracellular signal-regulated kinase
      (ERK)-dependent manner.

PMID- 15998293
TI  - Syntaxin 5 interacts specifically with presenilin holoproteins and affects
      processing of betaAPP in neuronal cells.
AB  - The specific roles of syntaxin 5 (Syx 5) in the interaction with presenilin (PS)
      and the accumulation of beta-amyloid precursor protein (betaAPP), as well as the
      secretion of beta-amyloid peptide (Abeta peptide) were examined in NG108-15
      cells. Syx 5, which localizes from the endoplasmic reticulum (ER) to the Golgi,
      bound to PS holoproteins, while the other Syxs studied did not. Among familial
      Alzheimer's disease (FAD)-linked PS mutants, PS1deltaE9, which lacks the
      endoproteolytic cleavage site, showed markedly decreased binding to Syx 5. The
      interaction domains in Syx 5 were mapped to the transmembrane region and to the
      cytoplasmic region containing the alpha-helical domains, which are distinct from
      the H3 (SNARE motif). Among all of the Syxs examined, only overexpression of Syx
      5 resulted in the accumulation of betaAPP in the ER to cis-Golgi compartment, an
      attenuation of the amount of the C-terminal fragment (APP-CTF) of betaAPP, and a
      reduction in the secretion of Abeta peptides. Furthermore, co-expression of Syx 5
      with C99 resulted in an increase in APP-CTF and suppressed Abeta secretion. Taken
      together, these results indicate that Syx 5 may play a specific role in the
      modulation of processing and/or trafficking of FAD-related proteins in neuronal
      cells by interaction with PS holoproteins in the early secretory compartment of
      neuronal cells.

PMID- 15998294
TI  - Effect of chronic gestational treatment with caffeine or theophylline on Group I
      metabotropic glutamate receptors in maternal and fetal brain.
AB  - Pregnant rats were treated throughout the gestational period with either caffeine
      or theophylline, and its effect on the metabotropic glutamate receptor (mGluRs)
      signal transduction pathway was studied in both maternal and fetal brain. In
      maternal brain, radioligand binding assays showed that chronic treatment with
      methylxanthines caused a significant decrease in the total number of mGluRs. This
      decrease was accompanied by an increase in receptor affinity. Immunodetection
      showed that mGluR1a and phospholipase C beta1 (PLCbeta1) were significantly
      decreased in response to chronic methylxanthine treatment, whereas alphaG(q/11)
      was not affected. A loss was also detected of PLC stimulation mediated by (S)-3,5
      dihydroxyphenylglycine (DHPG), a selective Group I mGluR agonist, suggesting
      desensitization of the mGluR/PLC pathway. In fetal brain, a loss in total mGluRs
      was observed in fetuses from mothers treated with caffeine or theophylline,
      without variation in receptor affinity. A decrease in mGluR1a, alphaG(q/11) and
      PLCbeta1 levels was also observed in response to treatment. However, changes
      detected in this immature tissue were not associated with variations in PLC
      activity. These results suggest that chronic caffeine or theophylline treatment
      down-regulates several mGluR/PLC transduction pathway components in both maternal
      and fetal brain, causing a loss of receptor responsiveness only in maternal
      brain.

PMID- 15998295
TI  - Developmental change in the calcium sensor for synaptic vesicle endocytosis in
      central nerve terminals.
AB  - Synaptic vesicle endocytosis is stimulated by calcium influx in mature central
      nerve terminals via activation of the calcium-dependent protein phosphatase,
      calcineurin. However, in different neuronal preparations calcineurin activity is
      either inhibitory, stimulatory or irrelevant to the process. We addressed this
      inconsistency by investigating the requirement for calcineurin activity in
      synaptic vesicle endocytosis during development, using vesicle recycling assays
      in isolated nerve terminals. We show that endocytosis occurs independently of
      calcineurin activity in immature nerve terminals, and that a calcineurin
      requirement develops 2-4 weeks after birth. Calcineurin-independent endocytosis
      is not due to the absence of calcineurin activity, since calcineurin is present
      in immature nerve terminals and its substrate, dynamin I, is dephosphorylated on
      depolarization. Calcineurin-independent endocytosis is calcium-dependent, since
      substitution of the divalent cation, barium, inhibits the process. Finally, we
      demonstrated that in primary neuronal cultures derived from neonatal rats,
      endocytosis that was initially calcineurin-independent developed a calcineurin
      requirement on maturation in culture. Our data account for the apparent
      inconsistencies regarding the role of calcineurin in synaptic vesicle
      endocytosis, and we propose that an unidentified calcium sensor exists to couple
      calcium influx to endocytosis in immature nerve terminals.

PMID- 15998296
TI  - Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice:
      possible involvement of Stat3 activation in the protection of neurons.
AB  - Interleukin (IL)-6 expression transiently increases in the acute phase of
      cerebral ischemia. To investigate the physiological significance of endogenous IL
      6 expression and to identify the main signal pathway for the action of IL-6, we
      administered anti-mouse IL-6 receptor monoclonal antibody (IL-6RA), which blocks
      IL-6 signaling, to mice immediately after a 45-min period of middle cerebral
      artery occlusion (MCAO). At 6 h after MCAO, IL-6RA administration had resulted in
      a significant reduction in the amount of phosphorylated signal transducer and
      activator of transcription-3 (Stat3) protein in the peri-infarct area of the
      cortex. At 24 h after MCAO, blockade of IL-6 signaling had led to an increase in
      number of apoptotic cells in the peri-infarct area and enlargement of the size of
      the infarct, and it had adversely affected neurological function. These results
      suggest that endogenous IL-6 plays a critical role in preventing damaged neurons
      from undergoing apoptosis in the acute phase of cerebral ischemia and that its
      role may be mediated by Stat3 activation.

PMID- 15998297
TI  - Reversal of non-hydroxy:alpha-hydroxy galactosylceramide ratio and unstable
      myelin in transgenic mice overexpressing UDP-galactose:ceramide
      galactosyltransferase.
AB  - The sphingolipids galactosylceramide and sulfatide are important for the
      formation and maintenance of myelin. Transgenic mice overexpressing the
      galactosylceramide synthesizing enzyme UDP-galactose:ceramide
      galactosyltransferase in oligodendrocytes display an up to four-fold increase in
      UDP-galactose:ceramide galactosyltransferase activity, which correlates with an
      increase in its products monogalactosyl diglyceride and non-hydroxy fatty acid
      containing galactosylceramide. Surprisingly, however, we observed a concomitant
      decrease in alpha-hydroxylated galactosylceramide such that total
      galactosylceramide in transgenic mice was almost unaltered. These data suggest
      that UDP-galactose:ceramide galactosyltransferase activity does not limit total
      galactosylceramide level. Furthermore, the predominance of alpha-hydroxylated
      galactosylceramide appeared to be determined by the extent to which non
      hydroxylated ceramide was galactosylated rather than by the higher affinity of
      UDP-galactose:ceramide galactosyltransferase for alpha-hydroxy fatty acid
      ceramide. The protein composition of myelin was unchanged with the exception of
      significant up-regulation of the myelin and lymphocyte protein. Transgenic mice
      were able to form myelin, which, however, was apparently unstable and
      uncompacted. These mice developed a progressive hindlimb paralysis and
      demyelination in the CNS, demonstrating that tight control of UDP
      galactose:ceramide galactosyltransferase expression is essential for myelin
      maintenance.

PMID- 15998298
TI  - Interactions between rho and gamma2 subunits of the GABA receptor.
AB  - The gamma-aminobutyric acid type C (GABA(C)) receptor is a ligand-gated chloride
      channel with distinct physiological and pharmacological properties. Although the
      exact subunit composition of native GABA(C) receptors has yet to be firmly
      established, there is general agreement that GABA rho subunits participate in
      their formation. Recent studies on white perch suggest that certain GABA rho
      subunits can co-assemble with the GABA(A) receptor gamma2 subunit to form a
      heteromeric receptor with electrophysiological properties that correspond more
      closely to the native GABA(C) receptor on retinal neurons than any of the
      homomeric rho receptors. In the present study we examined the interactions among
      various perch GABA rho and gamma2 subunits. When co-expressed in Xenopus oocytes,
      the gamma2 subunit co-immunoprecipitated with Flag-tagged perch rho1A, rho1B, and
      rho2B subunits, but not with the Flag-tagged perch rho2A subunit.
      Immunocytochemical studies indicated that the membrane surface expression of the
      gamma2 subunit was detected only when it was co-expressed with perch rho1A,
      rho1B, or rho2B subunit, but not with the perch rho2A subunit or when expressed
      alone. In addition, co-immunoprecipitation of perch rho1B and gamma2 subunits was
      also detected in protein samples of the teleost retina. Taken together, these
      findings suggest that a heteromeric rho(gamma2) receptor could represent one form
      of GABA(C) receptor on retinal neurons.

PMID- 15998299
TI  - The mechanism of SR95531 inhibition at GABA receptors examined in human
      alpha1beta1 and alpha1beta1gamma2S receptors.
AB  - We examined the interaction of GABA and the competitive inhibitor SR95531 at
      human alpha1beta1gamma2S and alpha1beta1 GABA(A) receptors expressed in Sf9
      cells. The efficacy and potency of inhibition depended on the relative timing of
      the GABA and SR95531 applications. In saturating (10 mM) GABA, the half
      inhibitory concentrations of SR95531 (IC50) when coapplied with GABA to
      alpha1beta1gamma2S or alpha1beta1 receptors were 49 and 210 microM for the peak
      and 18 and 130 microM for the plateau current, respectively. Our data are
      explained by an inhibition mechanism in which SR95531 and GABA bind to two sites
      on the receptor where the binding of GABA allows channel opening but SR95531 does
      not. The SR95531 affinity for both receptor types was approximately 200 nM and
      the binding rate was found to be 10-fold faster than that for GABA. The dual
      binding-site model gives insights into the differential effects of GABA and
      SR95531 on the peak and plateau currents. The model predicts the effect of
      SR95531 on GABA currents in the synapse (GABA concentration approximately mM) and
      at extrasynaptic (GABA concentration < or = microM) sites. The IC50 (50-100 nM)
      for the synaptic response to SR95531 was insensitive to the GABA affinity of the
      receptors whereas the IC50 (50-800 nM) for extrasynaptic inhibition correlated
      with the GABA affinity.

PMID- 15998300
TI  - Two distinct regulatory mechanisms of neurotransmitter release by
      phosphatidylinositol 3-kinase.
AB  - Recent studies have indicated that various growth factors are involved in
      synaptic functions; however, the precise mechanisms remain unclear. In order to
      elucidate the molecular mechanisms of the growth factor-mediated regulation of
      presynaptic functions, the effects of epidermal growth factor (EGF) and insulin
      like growth factor-1 (IGF-1) on neurotransmitter release were studied in rat PC12
      cells. Brief treatment with EGF and IGF-1 enhanced Ca2+-dependent dopamine
      release in a concentration-dependent manner. EGF activated both mitogen-activated
      protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-kinase) pathways,
      and the EGF-dependent enhancement of DA release was suppressed by a MAPK kinase
      inhibitor as well as by PI3-kinase inhibitors. In striking contrast, IGF-1
      activated the PI3-kinase pathway but not the MAPK pathway, and IGF-1-dependent
      enhancement was suppressed by a PI3-kinase inhibitor but not by a MAPK kinase
      inhibitor. The enhanced green fluorescent protein-tagged pleckstrin homology (PH)
      domain of protein kinase B, which selectively binds to phosphatidylinositol 3,4
      bisphosphate and phosphatidylinositol 3,4,5-triphosphate, was translocated to the
      plasma membrane after treatment with either EGF or NGF. By contrast, no
      significant redistribution was induced by IGF-1. These results indicate that PI3
      kinase participates in the enhancement of neurotransmitter release by two
      distinct mechanisms: EGF and NGF activate PI3-kinase in the plasma membrane,
      whereas IGF-1 activates PI3-kinase possibly in the intracellular membrane,
      leading to enhancement of neurotransmitter release in a MAPK-dependent and 
      independent manner respectively.

PMID- 15998301
TI  - Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain,
      which persists into early adulthood.
AB  - Prenatal and early postnatal zinc deficiency impairs learning and memory and
      these deficits persist into adulthood. A key modulator in this process may be the
      NMDA receptor; however, effects of zinc deficiency on the regulation of NMDA
      receptor activity are not well understood. Female Sprague-Dawley rats were fed
      diets containing 7 (zinc deficient, ZD), 10 (marginally zinc deficient, MZD) or
      25 (control) mg Zn/g diet preconception through postnatal day (PN) 20, at which
      time pups were weaned onto their maternal or control diet. Regulation of NMDA
      receptor expression was examined at PN2, PN11, and PN65. At PN2, expression of
      whole brain NMDA receptor subunits NR1, NR2A, and NR2B was lower in pups from
      dams fed ZD and MZD compared to controls, as analyzed using relative RT-PCR and
      immunoblotting. At PN11, whole brain and hippocampi NR1, NR2A, NR2B and PSA-NCAM
      (polysialic acid-neural cell adhesion molecule) expression and the number of PSA
      NCAM immunoreactive cells were lower in pups from dams fed ZD compared to
      controls. Whole brain brain-derived neurotrophic factor (BDNF) and nerve growth
      factor (NGF) concentrations were lower in pups from dams fed ZD or both low zinc
      diets, respectively. Whole brain NR1 expression remained lower in previously zinc
      deficient rats at PN65. These data indicate potential mechanisms through which
      developmental zinc deficiency can impair learning and memory later in life.

PMID- 15998302
TI  - Down-regulation of Dickkopf 3, a regulator of the Wnt signalling pathway, in
      elderly schizophrenic subjects.
AB  - The aetiology of schizophrenia is complex and the pathological mechanisms
      involved are still not fully understood. The aim of this project was to gain
      insight into the underlying molecular changes occurring in schizophrenia through
      the analysis of gene expression. Using suppression subtractive hybridization to
      isolate differentially expressed genes in superior temporal cortex (BA22), we
      detected one prominent sequence with reduced expression in schizophrenia and
      represented in at least nine clones. This was then selected for further
      validation. This 190-bp partial transcript showed identity to part of the
      Dickkopf-3 (Dkk3) gene sequence. Differential expression was initially confirmed
      in BA22 by slot blot hybridization where expression was decreased by 35% (p <
      0.026). These results were further authenticated in a larger panel (12 control
      and 11 schizophrenia cases) using SYBR Green I real-time quantitative RT-PCR, in
      which a 41% decrease in expression of Dkk3 mRNA in schizophrenia was obtained (p
      < 0.012). Furthermore, using in situ hybridization, Dkk3 mRNA was shown to be
      abundantly expressed in cortical neurones, with prominent expression in layers
      II/III and V/VI of BA22. Dkk3 belongs to a novel family of Dkk proteins, which
      have been shown to be potent inhibitors of the neurodevelopmental wingless (Wnt)
      signalling pathway, and is therefore a putative candidate for further
      investigation into the aetiology of schizophrenia.

PMID- 15998303
TI  - Identification and characterization of a novel family of Drosophila beta
      adrenergic-like octopamine G-protein coupled receptors.
AB  - Insect octopamine receptors carry out many functional roles traditionally
      associated with vertebrate adrenergic receptors. These include control of
      carbohydrate metabolism, modulation of muscular tension, modulation of sensory
      inputs and modulation of memory and learning. The activation of octopamine
      receptors mediating many of these actions leads to increases in the levels of
      cyclic AMP. However, to date none of the insect octopamine receptors that have
      been cloned have been convincingly shown to be capable of directly mediating
      selective and significant increases in cyclic AMP levels. Here we report on the
      identification and characterization of a novel, neuronally expressed family of
      three Drosophila G-protein coupled receptors that are selectively coupled to
      increases in intracellular cyclic AMP levels by octopamine. This group of
      receptors, DmOct beta1R (CG6919), DmOct beta2R (CG6989) and DmOct beta3R (CG7078)
      shows homology to vertebrate beta-adrenergic receptors. When expressed in Chinese
      hamster ovary cells all three receptors show a strong preference for octopamine
      over tyramine for the accumulation of cyclic AMP but show unique pharmacological
      profiles when tested with a range of synthetic agonists and antagonists. Thus,
      the pharmacological profile of individual insect tissue responses to octopamine
      might vary with the combination and the degree of expression of the individual
      octopamine receptors present.

PMID- 15998304
TI  - ERECTA receptor-like kinase and heterotrimeric G protein from Arabidopsis are
      required for resistance to the necrotrophic fungus Plectosphaerella cucumerina.
AB  - Arabidopsis resistance to the necrotrophic fungus Plectosphaerella cucumerina is
      complex and depends on the ethylene, jasmonic acid and salicylic acid signaling
      pathways. A quantitative trait loci (QTL) analysis of resistance to this fungus
      was performed using two populations of recombinant inbred lines. Three loci QRP1
      QRP3 (for Quantitative Resistance to Plectosphaerella) were identified and mapped
      on chromosome 2 (QRP1 and QRP2) and 5 (QRP3). QRP1, the locus showing the
      strongest effect, was found to correspond to the ERECTA (ER) gene that encodes a
      receptor-like-kinase (RLK), which has been previously implicated in plant
      development, and resistance to the bacterium Ralstonia solanacearum. The leucine
      rich repeat and the kinase domains of ERECTA were specifically required for
      resistance to P. cucumerina, as er mutant alleles impaired in any of these
      domains showed enhanced susceptibility to this fungus, but not to other virulent
      pathogens. The involvement of the ER-signaling pathway in resistance to P.
      cucumerina was supported by the fact that three mutants defective in this
      pathway, elk2, elk5 and elk4 (agb1-1), which encodes the beta-subunit of
      Arabidopsis heterotrimeric G protein, were also impaired in their resistance to
      this fungus. The putative function of the Arabidopsis heterotrimeric G protein in
      resistance to P. cucumerina suggested by the enhanced susceptibility of agb1-1
      was corroborated by the demonstration that a null allele (gpa1-4) of the G
      protein alpha-subunit showed enhanced resistance to this pathogen. Deposition of
      beta-1,3-glucan callose at infection sites was specifically impaired in er-1 and
      agb1-1 mutants upon P. cucumerina inoculation. Taken together, these data suggest
      a putative function of ERECTA and heterotrimeric G protein in P. cucumerina
      perception.

PMID- 15998305
TI  - Cell wall extension results in the coordinate separation of parallel
      microfibrils: evidence from scanning electron microscopy and atomic force
      microscopy.
AB  - Enlargement of the cell wall requires separation of cellulose microfibrils,
      mediated by proteins such as expansin; according to the multi-net growth
      hypothesis, enlargement passively reorients microfibrils. However, at the
      molecular scale, little is known about the specific movement of microfibrils. To
      find out, we examined directly changes in microfibril orientation when walls were
      extended slowly in vitro under constant load (creep). Frozen-thawed cucumber
      hypocotyl segments were strained by 20-30% by incubation in pH 4.5 buffer or by
      incubation of heat-inactivated segments in alpha-expansin or a fungal
      endoglucanase (Cel12A). Subsequently, the innermost layer of the cell wall was
      imaged, with neither extraction nor homogenization, by field-emission scanning
      electron microscopy (FESEM) and atomic force microscopy (AFM). AFM images
      revealed that sample preparation for FESEM did not appreciably alter cell wall
      ultrastructure. In both FESEM and AFM, images from extended and non-extended
      samples appeared indistinguishable. To quantify orientational order, we used a
      novel algorithm to characterize the fast Fourier transform of the image as a
      function of spatial frequency. For both FESEM and AFM images, the transforms of
      non-extended samples were indistinguishable from those of samples extended by
      alpha-expansin or Cel12A, as were AFM images of samples extended by acidic
      buffer. We conclude that cell walls in vitro can extend slowly by a creep
      mechanism without passive reorientation of innermost microfibrils, implying that
      wall loosening agents act selectively on the cross-linking polymers between
      parallel microfibrils, rather than more generally on the wall matrix.

PMID- 15998306
TI  - Altered microtubule dynamics by expression of modified alpha-tubulin protein
      causes right-handed helical growth in transgenic Arabidopsis plants.
AB  - The proper organization of cortical microtubule arrays is essential for
      anisotropic growth in plants but how distinct array patterns are formed is not
      understood. Here, we report a relationship between microtubule dynamics and array
      organization using transgenic plants expressing modified tubulins. When green
      fluorescent protein (GFP) or a hemaglutinin epitope tag was fused to the N
      terminus of tubulins and expressed in Arabidopsis plants, these tubulins were
      incorporated into microtubules along with endogenous tubulins. Plants expressing
      the modified beta-tubulins were phenotypically normal and possessed transversely
      oriented cortical arrays in the epidermal cells of the root elongation zone;
      however, the expression of modified alpha-tubulins caused right-handed helical
      growth, increased trichome branching, and a shallow left-handed (S-form) helical
      array organization. In cells expressing the modified alpha-tubulins, microtubule
      dynamicity was suppressed and polymerization was promoted, and GFP-EB1 (End
      Binding 1) labeled larger regions of the microtubule end more frequently, when
      compared with control cells. We propose that the N-terminal appendage introduced
      into alpha-tubulin inhibits GTP hydrolysis, thus producing polymerization-prone
      microtubules with an extended GTP cap. Consistent with this interpretation,
      plants expressing an alpha-tubulin mutated in the GTPase-activating domain
      exhibited similar microtubule properties, with regard to dynamics and the
      localization of GFP-EB1, and showed right-handed helical growth.

PMID- 15998307
TI  - Orphan transcripts in Arabidopsis thaliana: identification of several hundred
      previously unrecognized genes.
AB  - Expressed sequence tags (ESTs) represent a huge resource for the discovery of
      previously unknown genetic information and functional genome assignment. In this
      study we screened a collection of 178 292 ESTs from Arabidopsis thaliana by
      testing them against previously annotated genes of the Arabidopsis genome. We
      identified several hundreds of new transcripts that match the Arabidopsis genome
      at so far unassigned loci. The transcriptional activity of these loci was
      independently confirmed by comparison with the Salk Whole Genome Array Data. To a
      large extent, the newly identified transcriptionally active genomic regions do
      not encode 'classic' proteins, but instead generate non-coding RNAs and/or small
      peptide-coding RNAs of presently unknown biological function. More than 560
      transcripts identified in this study are not represented by the Affymetrix
      GeneChip arrays currently widely used for expression profiling in A. thaliana.
      Our data strongly support the hypothesis that numerous previously unknown genes
      exist in the Arabidopsis genome.

PMID- 15998308
TI  - Necrotizing activity of five Botrytis cinerea endopolygalacturonases produced in
      Pichia pastoris.
AB  - Five Botrytis cinerea endopolygalacturonase enzymes (BcPGs) were individually
      expressed in Pichia pastoris, purified to homogeneity and biochemically
      characterized. While the pH optima of the five enzymes were similar
      (approximately pH 4.5) the maximum activity of individual enzymes differed
      significantly. For hydrolysis of polygalacturonic acid (PGA), the V(max,app)
      ranged from 10 to 900 U mg(-1), while the K(m,app) ranged from 0.16 to 0.6 mg ml(
      1). Although all BcPGs are true endopolygalacturonases, they apparently have
      different modes of action. PGA hydrolysis by BcPG1, BcPG2 and BcPG4 leads to the
      transient accumulation of oligomers with DP < 7, whereas PGA hydrolysis by BcPG3
      and BcPG6 leads to the immediate accumulation of monomers and dimers. The
      necrotizing activity (NA) of all BcPGs was tested separately in tomato, broad
      bean and Arabidopsis thaliana. They showed different NAs on these plants. BcPG1
      and BcPG2 possessed the strongest NA as tissue collapse was observed within 10
      min after infiltration of broad bean leaves. The amino acid (aa) D192A
      substitution in the active site of BcPG2 not only abolished enzyme activity but
      also the NA, indicating that the NA is dependent on enzyme activity. Furthermore,
      deletion of the Bcpg2 gene in B. cinerea resulted in a strong reduction in
      virulence on tomato and broad bean. Primary lesion formation was delayed by
      approximately 24 h and the lesion expansion rate was reduced by 50-85%. These
      data indicate that BcPG2 is an important virulence factor for B. cinerea.

PMID- 15998309
TI  - Flavohaemoglobin HmpX from Erwinia chrysanthemi confers nitrosative stress
      tolerance and affects the plant hypersensitive reaction by intercepting nitric
      oxide produced by the host.
AB  - Host cells respond to infection by generating nitric oxide (NO) as a cytotoxic
      weapon to facilitate killing of invading microbes. Bacterial flavohaemoglobins
      are well-known scavengers of NO and play a crucial role in protecting animal
      pathogens from nitrosative stress during infection. Erwinia chrysanthemi, which
      causes macerating diseases in a wide variety of plants, possesses a
      flavohaemoglobin (HmpX) whose function in plant pathogens has remained unclear.
      Here we show that HmpX consumes NO and prevents inhibition by NO of cell
      respiration, indicating a role in protection from nitrosative stress.
      Furthermore, infection of Saintpaulia ionantha plants with an HmpX-deficient
      mutant of E. chrysanthemi revealed that the lack of NO scavenging activity causes
      the accumulation of unusually high levels of NO in host tissue and triggers
      hypersensitive cell death. Introduction of the wild-type hmpX gene in an
      incompatible strain of Pseudomonas syringae had a dramatic effect on the
      hypersensitive cell death in soya bean cell suspensions, and markedly reduced the
      development of macroscopic symptoms in Arabidopsis thaliana plants. These
      observations indicate that HmpX not only protects against nitrosative stress but
      also attenuates host hypersensitive reaction during infection by intercepting NO
      produced by the plant for the execution of the hypersensitive cell death
      programme.

PMID- 15998310
TI  - ROSINA (RSI), a novel protein with DNA-binding capacity, acts during floral organ
      development in Antirrhinum majus.
AB  - Petal and stamen identity of the Antirrhinum majus flower is under the genetic
      control of the floral homeotic gene DEFICIENS (DEF). To isolate factors involved
      in the regulation of DEF gene activity, a promoter segment of this B-function
      gene, containing cis-acting regulatory elements, was used to identify the novel
      trans-acting factor ROSINA (RSI). RSI does not show an extended similarity with
      any gene product present in the database. Rather RSI constitutes a protein that
      contains domains similar to known proteins from organisms of different phyla. The
      capacity of RSI to bind a sequence element of the DEF promoter, its spatial and
      temporal expression pattern together with the phenotype of RSI-RNAi interference
      plants as well as RSI over-expression in Arabidopsis thaliana suggest that RSI is
      a putative regulator of DEF gene activity in A. majus.

PMID- 15998311
TI  - Interaction of Arabidopsis BRASSINOSTEROID-INSENSITIVE 1 receptor kinase with a
      homolog of mammalian TGF-beta receptor interacting protein.
AB  - Brassinosteroids (BRs) regulate multiple aspects of plant growth and development
      and require an active BRASSINOSTEROID-INSENSITIVE 1 (BRI1) receptor
      serine/threonine kinase for hormone perception and signal transduction. In
      mammals, the transforming growth factor-beta (TGF-beta) family of polypeptides
      modulate numerous aspects of development and are perceived at the cell surface by
      a complex of type I and type II TGF-beta receptor serine/threonine kinases. TGF
      beta receptor interacting protein (TRIP-1) is a cytoplasmic substrate of the TGF
      beta type II receptor kinase and plays a role in TGF-beta signaling. TRIP-1 is a
      WD domain protein that also functions as an essential subunit of the eIF3
      eukaryotic translation initiation factor in animals, yeast and plants. We
      previously cloned putative TRIP-1 homologs from bean and Arabidopsis and found
      that transgenic Arabidopsis plants expressing antisense TRIP-1 RNA exhibited a
      broad range of developmental defects including some morphological characteristics
      that resemble the phenotype of BR-deficient and -insensitive mutants. We now show
      that the BRI1 kinase domain phosphorylates Arabidopsis TRIP-1 on three specific
      sites in vitro (Thr-14, Thr-89 and either Thr-197 or Ser-198). Co
      immunoprecipitation experiments using antibodies against TRIP-1, BRI1 and various
      fusion proteins strongly suggest that TRIP-1 and BRI1 also interact directly in
      vivo. These findings support a role for TRIP-1 in the molecular mechanisms of BR
      regulated plant growth and development, possibly as a cytoplasmic substrate of
      the BRI1 receptor kinase.

PMID- 15998312
TI  - Siderophore-mediated upregulation of Arabidopsis ferritin expression in response
      to Erwinia chrysanthemi infection.
AB  - Ferritins are multimeric iron storage proteins encoded by a four-member gene
      family in Arabidopsis (AtFer1-4). To investigate whether iron sequestration in
      ferritins is a part of an iron-withholding defense system induced in response to
      bacterial invasion, we used Arabidopsis thaliana as a susceptible host for the
      pathogenic bacterium Erwinia chrysanthemi. In this study, we used a T-DNA
      insertion mutant line to show that the lack of a functional AtFer1 gene resulted
      in an enhanced susceptibility of Arabidopsis plants to E. chrysanthemi. We found
      that the AtFer1 gene is upregulated during infection, with a biphasic
      accumulation of the transcript at critical time points 0.5 and 24 h post
      infection (p.i.). The activation of AtFer1 expression observed at 24 h p.i. was
      independent of the iron-dependent regulatory sequence (IDRS) known to mediate the
      transcriptional response of the AtFer1 gene to iron excess and to nitric oxide.
      Upregulation of AtFer1 gene expression was compromised after inoculation with an
      E. chrysanthemi siderophore null mutant. Infiltration of the purified
      siderophores chrysobactin and desferrioxamine strongly increased AtFer1
      transcript abundance and it did not occur with the iron-loaded forms of these
      siderophores. We found that neither oxidative stress nor nitric oxide was
      involved in the plant response to chrysobactin. Our data show that ferritin
      accumulation during infection of Arabidopsis by E. chrysanthemi is a basal
      defense mechanism which is mainly activated by bacterial siderophores. The
      potential role of siderophores in this process is discussed.

PMID- 15998313
TI  - Disruption of the cellulose synthase gene, AtCesA8/IRX1, enhances drought and
      osmotic stress tolerance in Arabidopsis.
AB  - Two allelic Arabidopsis mutants, leaf wilting 2-1 and leaf wilting 2-2 (lew2-1
      and lew2-2 ), were isolated in a screen for plants with altered drought stress
      responses. The mutants were more tolerant to drought stress as well as to NaCl,
      mannitol and other osmotic stresses. lew2 mutant plants accumulated more abscisic
      acid (ABA), proline and soluble sugars than the wild type. The expression of a
      stress-inducible marker gene RD29A, a proline synthesis-related gene P5CS
      (pyrroline-5-carboxylate synthase) and an ABA synthesis-related gene SDR1
      (alcohol dehydrogenase/reductase) was higher in lew2 than in the wild type. Map
      based cloning revealed that the lew2 mutants are new alleles of the AtCesA8/IRX1
      gene which encodes a subunit of a cellulose synthesis complex. Our results
      suggest that cellulose synthesis is important for drought and osmotic stress
      responses including drought induction of gene expression.

PMID- 15998315
TI  - Virus-induced gene silencing in tomato fruit.
AB  - Virus-induced gene silencing (VIGS) is a powerful tool for the study of gene
      function in plants. Here we report that either by syringe-infiltrating the
      tobacco rattle virus (TRV)-vector into the surface, stem or carpopodium of a
      tomato fruit attached to the plant or by vacuum-infiltrating into a tomato fruit
      detached from the plant, TRV can efficiently spread and replicate in the tomato
      fruit. Although VIGS can be performed in tomato fruit by all of the means
      mentioned above, the most effective method is to inject the TRV-vector into the
      carpopodium of young fruit attached to the plant about 10 days after pollination.
      Several reporter genes related to ethylene responses and fruit ripening,
      including LeCTR1 and LeEILs genes, were also successfully silenced by this method
      during fruit development. In addition, we found that the silencing of the LeEIN2
      gene results in the suppression of tomato fruit ripening. The results of our
      study indicate that the application of VIGS techniques by the described methods
      can be successfully applied to tomato fruit and is a valuable tool for studying
      functions of the relevant genes during fruit developing.

PMID- 15998314
TI  - Heat shock protein 90 and its co-chaperone protein phosphatase 5 interact with
      distinct regions of the tomato I-2 disease resistance protein.
AB  - Recent data suggest that plant disease resistance (R) proteins are present in
      multi-protein complexes. Tomato R protein I-2 confers resistance against the
      fungal pathogen Fusarium oxysporum. To identify components of the I-2 complex, we
      performed yeast two-hybrid screens using the I-2 leucine-rich repeat (LRR) domain
      as bait, and identified protein phosphatase 5 (PP5) as an I-2 interactor.
      Subsequent screens revealed two members of the cytosolic heat shock protein 90
      (HSP90) family as interactors of PP5. By performing in vitro protein-protein
      interaction analysis using recombinant proteins, we were able to show a direct
      interaction between I-2 and PP5, and between I-2 and HSP90. The N-terminal part
      of the LRR domain was found to interact with HSP90, whereas the C-terminal part
      bound to PP5. The specific binding of HSP90 to the N-terminal region of the I-2
      LRR domain was confirmed by co-purifying HSP90 from tomato lysate using
      recombinant proteins. Similarly, the interaction between PP5 and HSP90 was
      established. To investigate the role of PP5 and HSP90 for I-2 function, virus
      induced gene silencing was performed in Nicotiana benthamiana. Silencing of HSP90
      but not of PP5 completely blocked cell death triggered by I-2, showing that HSP90
      is required for I-2 function. Together these data suggest that R proteins
      require, like steroid hormone receptors in animal systems, an HSP90/PP5 complex
      for their folding and functioning.

PMID- 15998316
TI  - Confocal microscopy of whole ovules for analysis of reproductive development: the
      elongate1 mutant affects meiosis II.
AB  - Analysis of female meiosis (megasporogenesis) and embryo sac development
      (megagametogenesis) in angiosperms is technically challenging because the cells
      are enclosed within the nucellus and ovule tissues of the female flower. This is
      in contrast to male sporogenesis and gametogenesis where development can readily
      be observed through the easily dissectable developing anthers. Observation of
      embryo sac development is a particular problem in crassinucellate ovules such as
      those of maize. To overcome the problems in observing reproductive development,
      we developed a simple Feulgen staining procedure optimized for use with confocal
      microscopy to observe reproductive progression in the crassinucellate ovules of
      maize. The procedure greatly facilitates the observation of nuclei and cell
      structures of all stages of megasporogenesis and embryo sac development. The high
      resolution obtained using the technique enabled us to readily visualize
      chromosomes from individual cells within ovule tissue samples of maize. A
      propidium iodide staining technique was also used and compared with the Feulgen
      based technique. Static cytometry of relative DNA content of individual nuclei
      was possible using Imaris software on both Feulgen and propidium iodide-stained
      samples. The techniques also proved successful for the observation of Arabidopsis
      and Hieracium aurantiacum female gametophyte and seed development, demonstrating
      the general applicability of the techniques. Using both staining methods, we
      analysed the maize meiotic mutant elongate1, which produces functional diploid
      instead of haploid embryo sacs. The precise defect in meiosis from which diploid
      embryo sacs arise in elongate1 has not previously been reported. We used confocal
      microscopy followed by static cytometry using Imaris software to show that the
      defect by which diploid embryo sacs arise in the maize mutant elongate1 is the
      absence of meiosis II with one of the dyad cells directly initiating
      megagametogenesis.

PMID- 15998317
TI  - Unconventional secretory routes: direct protein export across the plasma membrane
      of mammalian cells.
AB  - The vast majority of extracellular proteins are exported from mammalian cells by
      the endoplasmic reticulum/Golgi-dependent secretory pathway. For poorly
      understood reasons, however, a heterogenous group of extracellular proteins has
      been discovered that does not make use of signal peptide-dependent secretory
      transport. Both the release mechanisms and the molecular identity of the
      secretory machines involved have remained elusive. Recent studies now have
      established a subgroup of unconventional secretory proteins capable of
      translocating from the cytoplasm directly across the plasma membrane to get
      access to the exterior of eukaryotic cells. This review aims to focus on a
      detailed comparison of the subcellular site of membrane translocation of various
      unconventional secretory proteins such as the proangiogenic molecule fibroblast
      growth factor-2 (FGF-2) and Leishmania hydrophilic acylated surface protein B
      (HASP B). A potential link between membrane translocation and quality control as
      an integral part of unconventional secretory processes is discussed.

PMID- 15998318
TI  - Protein sorting to the storage vacuoles of plants: a critical appraisal.
AB  - The vacuole of plant cells is no longer considered to be a single compartment
      with multifunctional properties. A lot of evidence now points to the presence of
      multiple functionally distinct vacuolar compartments, some existing side by side
      in the same cell. As a consequence, the plant Golgi apparatus is faced with the
      problem of recognizing proteins destined for lytic and storage vacuoles and
      segregating them individually from the flow of secretory proteins to the cell
      surface. In contrast to acid hydrolases, which are sorted by BP-80-like receptors
      at the trans-Golgi of plant cells, the identification of receptors for storage
      proteins has in many ways resembled 'the search for the Holy Grail'. There are
      several candidates for storage protein receptors, but in no single case is the
      evidence entirely convincing. Much of the problem lies in the lack of consensus,
      sorting sequences in the proteins investigated. Other difficulties stem from 'out
      of-context' heterologous expression studies. Evidence is now accumulating for the
      participation of hydrophobic sequences in inducing the formation of protein
      aggregates in the early Golgi apparatus, for which classical sorting receptors do
      not appear to be necessary. This review critically examines the current situation
      and contrasts the differences between data obtained in situ and data obtained
      transgenically. It highlights the so-called 'dense-vesicle' pathway and
      culminates with a discussion on the hitherto neglected problem of the
      intracellular transport of storage protein processing enzymes.

PMID- 15998319
TI  - Septins: traffic control at the cytokinesis intersection.
AB  - The physical division of one cell into two requires the highly orchestrated
      separation of genetic and cytoplasmic contents during M phase of the cell cycle.
      Mitosis, the physical segregation of the genetic material of a cell into two
      daughter cells, has traditionally received more attention than cytokinesis, the
      partitioning of the cytoplasmic contents, yet clearly the two processes must be
      intimately co-ordinated and tightly regulated. While plant cells divide by the
      formation of a membranous cell barrier called the phragmoplast, animal cell
      division is largely driven by contraction of an actomyosin ring. However, recent
      evidence has suggested that membranes derived from one or more intracellular
      compartments are also required to break the cytoplasmic bridge connecting two
      dividing cells during late telophase. In this review, we focus on studies of
      animal cell cytokinesis that support a requirement for specific endomembrane
      fusion during fission, define molecular components of the membrane fusion
      apparatus that may be involved and point to possible roles for an emerging family
      of cytoskeletal proteins, the septins, in this process.

PMID- 15998320
TI  - Maturation of Rhodococcus equi-containing vacuoles is arrested after completion
      of the early endosome stage.
AB  - Rhodococcus equi is a facultative intracellular bacterium that can cause
      bronchopneumonia in foals and AIDS patients. Here, we have analyzed R. equi
      containing vacuoles (RCVs) in murine macrophages by confocal laser scanning
      microscopy, by transmission electron microscopy and by immunochemistry upon
      purification. We show that RCVs progress normally through the early stages of
      phagosome maturation acquiring PI3P, early endosome antigen-1, and Rab5, and
      loosing all or much of them within minutes. Although mature RCVs possess the
      normally late endocytic markers, lysosome-associated membrane proteins,
      lysobisphosphatidic acid and Rab7, they lack other hallmark features of late
      endocytic organelles such as possession of cathepsin D, acid beta-glucuronidase,
      proton-pumping ATPase and the ability to fuse with prelabeled lysosomes.
      Bacterial strains possessing a virulence-associated plasmid maintain a
      nonacidified compartment for 48 h, whereas isogenic strains lacking such plasmids
      acidify progressively. In summary, RCVs represent a novel phagosome maturation
      stage positioned after completion of the early endosome stage and before reaching
      a fully mature late endosome compartment. In addition, vacuole biogenesis can be
      influenced by bacterial plasmids.

PMID- 15998321
TI  - Cellular localization and stimulation-associated distribution dynamics of
      syntaxin-1 and syntaxin-3 in gastric parietal cells.
AB  - Syntaxins are differentially localized in polarized cells and play an important
      role in vesicle trafficking and membrane fusion. These soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) proteins are believed to be
      involved in tubulovesicle trafficking and membrane fusion during the secretory
      cycle of the gastric parietal cell. We examined the cellular localization and
      distribution of syntaxin-1 and syntaxin-3 in rabbit parietal cells. Fractionation
      of gastric epithelial cell membranes showed that syntaxin-1 was more abundant in
      a fraction enriched in apical plasma membranes, whereas syntaxin-3 was found
      predominantly in the H,K-ATPase-rich tubulovesicle fraction. We also examined the
      cellular localization of syntaxins in cultured parietal cells. Parietal cells
      were infected with CFP-syntaxin-1 and CFP-syntaxin-3 adenoviral constructs.
      Fluorescence microscopy of live and fixed cells demonstrated that syntaxin-1 was
      primarily on the apical membrane vacuoles of infected cells, but there was also
      the expression of syntaxin-1 in a subadjacent cytoplasmic compartment. In
      resting, non-secreting parietal cells, syntaxin-3 was distributed throughout the
      cytoplasmic compartment; after stimulation, syntaxin-3 translocated to the apical
      membrane vacuoles, there co-localizing with H,K-ATPase, syntaxin-1 and F-actin.
      The differential location of these syntaxin isoforms in gastric parietal cells
      suggests that these proteins may be critical for maintaining membrane compartment
      identity and that they may play important, but somewhat different, roles in the
      membrane recruitment processes associated with secretory activation.

PMID- 15998322
TI  - Akt regulates the subcellular localization of the Rab27a-binding protein JFC1 by
      phosphorylation.
AB  - Here, we show that the Rab27a-binding protein JFC1/Slp1 (synaptotagmin-like
      protein) is regulated by Akt-mediated phosphorylation. Using the phosphatase and
      tensin homolog-null LNCaP cells and the phosphatidylinositol 3-kinase inhibitor
      LY294002, we show that the phosphorylation of endogenous JFC1 is dependent on the
      phosphatidylinositol 3-kinase/Akt pathway. JFC1 was phosphorylated in cells
      expressing a constitutively active Akt, confirming that it is an Akt substrate in
      vivo. Direct phosphorylation of JFC1 by Akt was confirmed in vitro. Using
      microcapillary high-performance liquid chromatography tandem mass spectrometry,
      we identified five Akt-phosphorylation sites in JFC1. By mutagenesis analysis and
      subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1
      at serine 241. JFC1 and Rab27a colocalize in the proximity of the plasma membrane
      in LNCaP cells. The interaction was confirmed by IP analysis and was abolished by
      the point mutation W83S in JFC1. Phosphorylation did not alter the ability of
      JFC1 to bind to Rab27a. Instead, phosphorylation by Akt dramatically decreased
      when JFC1 was bound to Rab27a. Finally, we show that as a consequence of in vivo
      phosphorylation, JFC1 dissociates from the membrane, promoting JFC1
      redistribution to the cytosol. Our results suggest that Akt regulates JFC1/Slp1
      function by phosphorylation and may have implications on Rab27a-containing
      vesicle secretion.

PMID- 15998323
TI  - Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of
      podosomes.
AB  - Haematopoietic cell kinase (Hck) is a protein tyrosine kinase of the Src family
      specifically expressed in phagocytes as two isoforms, p59Hck and p61Hck, present
      at the plasma membrane and lysosomes, respectively. We report that ectopic
      expression of a constitutively active mutant of p61Hck (p61Hck(ca)) triggered the
      de novo formation of actin-rich rings at the ventral face of the cells that we
      characterized as bona fide podosome rosettes, structures involved in cell
      migration. Their formation required the adaptor domains and the kinase activity
      of p61Hck, the integrity of microfilament and microtubule networks and concerted
      action of Cdc42, Rac and Rho. Podosome rosette formation was either abolished
      when p61Hck(ca) was readdressed from lysosomes to the cytosol or triggered when
      p59Hck(ca) was relocalized to lysosomes. Lysosomal markers were present at
      podosome rosettes. By stimulating exocytosis of p61Hck(ca) lysosomes with a
      calcium ionophore, the formation of podosome rosettes was enhanced.
      Interestingly, we confirm that, in human macrophages, Hck and lysosomal markers
      were present at podosomes which were spatially reorganized as clusters, a
      foregoing step to form rosettes, upon expression of p61Hck(ca). We propose that
      lysosomes, under the control of p61Hck, are involved in the biogenesis of
      podosomes, a key phenomenon in the migration of phagocytes.

PMID- 15998324
TI  - CeVPS-27 is an endosomal protein required for the molting and the endocytic
      trafficking of the low-density lipoprotein receptor-related protein 1 in
      Caenorhabditis elegans.
AB  - Class E vacuolar protein-sorting (Vps) proteins were first described in yeast as
      being involved in receptor-mediated endocytosis and multivesicular body
      formation. Inactivation by RNA interference of the class E VPS genes of the
      nematode Caenorhabditis elegans revealed heterogeneous phenotypes. We have
      further characterized the role of the essential gene Cevps-27, ortholog of human
      hepatocyte growth factor-regulated tyrosine kinase substrate, during the
      development of C. elegans. Use of green fluorescent protein fusion constructs and
      antibody staining revealed that Cevps-27 localizes to endosomal membranes. It is
      widely expressed but enriched in epithelial cells. Cevps-27 mutants presented
      enlarged endosomal structures and an accumulation of autophagic vesicles as
      revealed by electron microscopy and the analysis of the autophagic marker LGG-1.
      Cevps-27 animals arrested at L2-L3 molt with an inability to degrade their old
      cuticle. This molting phenotype was more severe when Cevps-27 worms were grown on
      suboptimal concentrations of cholesterol. Furthermore, defective endocytic
      trafficking of the low-density lipoprotein receptor-related protein 1 (LRP-1) was
      also observed in Cevps-27 mutants. These results indicate that CeVPS-27 is
      required for endosomal and autophagic pathways in C. elegans and plays a crucial
      role in the control of molting through LRP-1 internalization and cholesterol
      traffic.

PMID- 15998325
TI  - Protein targeting from malaria parasites to host erythrocytes.
AB  - Malaria is caused by obligate intracellular parasites, which live in host
      erythrocytes and remodel these cells to provide optimally for their own needs.
      Plasmodium falciparum, responsible for malaria in humans, transports many
      proteins into erythrocytes which help the parasite survive in the host. The
      recent discovery of a host cell-targeting sequence present in both soluble and
      transmembrane P. falciparum proteins provoked a discussion on the potential
      mechanisms of parasite protein entry into infected erythrocytes which is
      summarized here.

PMID- 15998326
TI  - Improving lip wrinkles: lipstick-related image analysis.
AB  - BACKGROUND/PURPOSE: The appearance of lip wrinkles is problematic if it is
      adversely influenced by lipstick make-up causing incomplete color tone, spread
      phenomenon and pigment remnants. It is mandatory to develop an objective
      assessment method for lip wrinkle status by which the potential of wrinkle
      improving products to lips can be screened. The present study is aimed at finding
      out the useful parameters from the image analysis of lip wrinkles that is
      affected by lipstick application. METHODS: The digital photograph image of lips
      before and after lipstick application was assessed from 20 female volunteers.
      Color tone was measured by Hue, Saturation and Intensity parameters, and time
      related pigment spread was calculated by the area over vermilion border by image
      analysis software (Image-Pro). The efficacy of wrinkle-improving lipstick
      containing asiaticoside was evaluated from 50 women by using subjective and
      objective methods including image analysis in a double-blind placebo-controlled
      fashion. RESULTS: The color tone and spread phenomenon after lipstick make-up
      were remarkably affected by lip wrinkles. The level of standard deviation by
      saturation value of image-analysis software was revealed as a good parameter for
      lip wrinkles. By using the lipstick containing asiaticoside for 8 weeks, the
      change of visual grading scores and replica analysis indicated the wrinkle
      improving effect. As the depth and number of wrinkles were reduced, the lipstick
      make-up appearance by image analysis also improved significantly. CONCLUSION: The
      lip wrinkle pattern together with lipstick make-up can be evaluated by the image
      analysis system in addition to traditional assessment methods. Thus, this
      evaluation system is expected to test the efficacy of wrinkle-reducing lipstick
      that was not described in previous dermatologic clinical studies.

PMID- 15998327
TI  - A systematic heuristic approach for feature selection for melanoma discrimination
      using clinical images.
AB  - BACKGROUND: Numerous features are derived from the asymmetry, border
      irregularity, color variegation, and diameter of the skin lesion in dermatology
      for diagnosing malignant melanoma. Feature selection for the development of
      automated skin lesion discrimination systems is an important consideration.
      METHODS: In this research, a systematic heuristic approach is investigated for
      feature selection and lesion classification. The approach integrates statistical
      , correlation-, histogram-, and expert system-based components. Using statistical
      and correlation measures, interrelationships among features are determined.
      Expert system analysis is performed to identify redundant features. The feature
      selection process is applied to 19 shape and color features for a clinical image
      data set containing 355 malignant melanomas, 125 basal cell carcinomas, 177
      dysplastic nevi, 199 nevocellular nevi, 139 seborrheic keratoses, and 45 vascular
      lesions. RESULTS: Experimental results show reduced lesion classification error
      rates based on condensing the shape and color feature set from 19 features to 13
      features using the feature selection process. Specifically, average test lesion
      classification error rates for discriminating malignant melanoma from non
      melanoma lesions were reduced from 26.6% for 19 features to 23.2% for 13 features
      over five randomly generated training and test sets. CONCLUSIONS: The
      experimental results show that the systematic heuristic approach for feature
      reduction can be successfully applied to achieve improved lesion discrimination.
      The feature reduction technique facilitates the elimination of redundant
      information that may inhibit lesion classification performance. The clinical
      application of this result is that automated skin lesion classification algorithm
      development can be fostered with systematic feature selection techniques.

PMID- 15998329
TI  - High resolution B-scan ultrasound of hypertrophic scars.
AB  - BACKGROUND: Ultrasonography has provided the means for objective and non-invasive
      monitoring of the dynamics of some skin diseases. The pathologic scars (keloids
      and hypertrophic scars) that have an increased content of collagen, and have been
      not analyzed by high-frequency ultrasound so far. The purpose of the present
      study was to determine the ecographic features of these scars with a view in
      developing a reliable method for assessing the effectiveness of different
      therapeutic approaches. METHODS: Six pathological scars from five patients were
      examined by a 20 MHz B-Scanner and compared with healthy skin of the same region.
      Densitometry analysis was performed with the aid of a dedicated software.
      RESULTS: All the pathologic scars studied showed an easily identified echo-poor
      image clearly demarcated from the surrounding not involved tissue. When they were
      analyzed by densitometry, the lesions had highly significant reduced
      densitometric values (7.6+/-4.7) compared with regional healthy skin (31.79+/
      10.8). CONCLUSION: The high-frequency ultrasonography is a suitable objective and
      non-invasive method for discriminating healthy from pathologic skin in
      hypertrophic scars and keloids.

PMID- 15998328
TI  - Detection of asymmetric blotches (asymmetric structureless areas) in dermoscopy
      images of malignant melanoma using relative color.
AB  - BACKGROUND: Dermoscopy, also known as dermatoscopy or epiluminescence microscopy
      (ELM), is a non-invasive, in vivo technique, which permits visualization of
      features of pigmented melanocytic neoplasms that are not discernable by
      examination with the naked eye. One prominent feature useful for melanoma
      detection in dermoscopy images is the asymmetric blotch (asymmetric structureless
      area). METHOD: Using both relative and absolute colors, blotches are detected in
      this research automatically by using thresholds in the red and green color
      planes. Several blotch indices are computed, including the scaled distance
      between the largest blotch centroid and the lesion centroid, ratio of total
      blotch areas to lesion area, ratio of largest blotch area to lesion area, total
      number of blotches, size of largest blotch, and irregularity of largest blotch.
      RESULTS: The effectiveness of the absolute and relative color blotch features was
      examined for melanoma/benign lesion discrimination over a dermoscopy image set
      containing 165 melanomas (151 invasive melanomas and 14 melanomas in situ) and
      347 benign lesions (124 nevocellular nevi without dysplasia and 223 dysplastic
      nevi) using a leave-one-out neural network approach. Receiver operating
      characteristic curve results are shown, highlighting the sensitivity and
      specificity of melanoma detection. Statistical analysis of the blotch features
      are also presented. CONCLUSION: Neural network and statistical analysis showed
      that the blotch detection method was somewhat more effective using relative color
      than using absolute color. The relative-color blotch detection method gave a
      diagnostic accuracy of about 77%.

PMID- 15998330
TI  - Regional and seasonal variations in facial sebum secretions: a proposal for the
      definition of combination skin type.
AB  - BACKGROUND/AIMS: Facial sebum secretions are known to change under various
      circumstances. Facial skin types have been categorized as oily, normal, dry, and
      combination types. However, these have been evaluated subjectively by individuals
      to date, and no objective accepted standard measurement method exists. The
      combination skin type is most common, but its definition is vaguer than the
      definitions of the other skin types. METHODS: We measured facial sebum secretions
      with Sebumeter. Sebum secretions were measured at five sites of the face
      seasonally for a year, in the same volunteers. Using the data obtained we
      developed a set of rules to define the combination skin type. RESULTS: Regional
      differences in sebum secretion were confirmed. Sebum secretions on forehead,
      nose, and chin were higher than on both cheeks. Summer was found to be the
      highest sebum-secreting season, and seasonal variations were found in the T- and
      U-zones. A mismatch of skin type in the T- and U-zones in more than two seasons
      appears to be close to subjective ratings of what is described as the
      'combination' skin type. CONCLUSION: We showed that the face shows definitive
      regional and seasonal variations in sebum secretion. To define the combination
      skin type, seasonal variations in sebum secretion should be considered in
      addition to regional variations.

PMID- 15998331
TI  - Non-invasive preoperative assessment of basal cell carcinoma of nodular and
      superficial types.
AB  - BACKGROUND/AIMS: Although various biophysical properties can be used to
      distinguish basal cell carcinoma (BCC) tissue from normal skin, none permits
      typing of the tumour. In this study, we assessed nodular (NBCC) and superficial
      (SBCC) types of BCC using three different non-invasive instruments and placed
      special emphasis on their clinical value as diagnostic tools. METHODS: We
      included 35 patients with 35 tumours (15 NBCC and 20 SBCC), which had been
      diagnosed clinically. All lesions were evaluated preoperatively with an
      instrument measuring electrical impedance (IMP). Methods for determining
      transepidermal water loss (TEWL) and laser Doppler (LD) were also used.
      Measurements were also made in healthy skin on the contralateral side as
      reference. The diagnosis was confirmed by histological examination. RESULTS: We
      found clear differences between the lesions and their reference values, using all
      three bioengineering techniques for NBCC and SBCC. The biophysical parameters of
      all types vary with anatomical location. Since most of the NBCC were located on
      the face and most SBCC on the trunk, their baseline impedance characteristics
      (i.e., impedance indices magnitude index (MIX) and imaginary part index (IMIX))
      differed significantly. We therefore compared delta (a difference between the
      reference and tumour) MIX and IMIX of NBCC and SBCC instead of the absolute
      figures. We found no significant differences in TEWL, blood flow and IMP between
      the two types of BCC and attribute this to biological variation and
      electromagnetic noise. CONCLUSIONS: As with LD and TEWL, definite differences in
      IMP were detected between healthy skin and BCC lesions. However, at this stage of
      development of the bioimpedance technique, we were unable to distinguish between
      the two types of BCC. An improved IMP device with semi- invasive probes or a more
      sophisticated type of data analysis may increase the diagnostic usefulness of the
      IMP method.

PMID- 15998332
TI  - Effect of hormonal replacement therapy on skin biophysical properties of
      menopausal women.
AB  - BACKGROUND/PURPOSE: Hormonal replacement therapy (HRT) has been shown in the past
      to influence well being as well as several somatic features in menopausal women.
      The aim of this analysis was to study the effect of HRT on various biophysical
      properties of the skin of menopausal women. Two sub-samples were built to test
      the effect (1) of 'short-term' HRT in recently menopausal women (n=15), and (2)
      the effect of 'medium- and long-term' HRT in menopausal women (n=78). METHODS:
      The analysis was performed on data from a study of 106 menopausal Caucasian women
      with apparent healthy skin. Self-report data on the menopausal status, the
      duration of the menopause, whether or not HRT has been taken and the duration of
      the HRT were collected. A series of biophysical measurements on the cheek, the
      forehead and the inner forearm were performed under controlled environmental
      conditions. Twenty women were menopausal for less than 5 years (eight with HRT
      for at least 1 year and seven who had never taken HRT) and 86 women for at least
      5 years (35 with HRT for at least 5 years and 43 who had never taken HRT).
      Analyses of covariance with adjustment for age were performed. RESULTS: With
      regard to skin colour, the measurements in women treated for at least 1 year were
      significantly higher for red intensity (a*) and lower for brightness (L*) on the
      forearm as compared with the non-treated women. Furthermore, yellow intensity
      (b*) mean values were higher on the forehead and the forearm in women treated for
      at least 5 years compared with the non-treated women. Concerning sebum casual
      level, the mean values were significantly higher on the forehead and the cheek in
      women treated for at least 5 years. Regarding skin surface parameters reflecting
      hydration, the mean values for capacitance on the forehead and the cheek were
      significantly higher in women treated for at least 5 years. Finally, as regards
      with skin relief, parameters mean values for amplitude and roughness on the
      forehead were significantly higher in women treated for at least 5 years.
      CONCLUSION: The skin colour parameters showed a higher red intensity value in
      menopausal women who had been treated for at least 1 year. In menopausal women
      who had been treated for at least 5 years, the biophysical measurements were
      significantly higher for the parameters reflecting hydration and sebum secretion,
      which generally decrease after the menopause. These features were associated with
      higher values for the yellow intensity parameter and the skin relief parameters
      on the forehead. Our results support the subjective impression and the clinical
      evaluation concerning the impact of HRT on the development and the evolution of
      some skin properties after menopause.

PMID- 15998333
TI  - Comparative evaporimetry in man.
AB  - BACKGROUND/AIMS: Transepidermal water loss (TEWL) measurements are frequently
      used; the most widely utilized instrument has been the open chamber device.
      Traditional open-chamber systems for measuring TEWL have limitations related to
      ambient and body-induced airflows near the probe, probe size, measurement site
      and angles. Recent technology provides a portable and battery-operated closed
      chamber Evaporimeter. It is presumably less affected by external factors such as
      room- or body-induced airflows, breathing or heating of the probe by the
      operators' hand. This study compares this commercial instrument, a closed chamber
      device, with a traditional open-chamber device. METHODS: Two open chamber devices
      and one closed chamber device were used in such a way that each instrument could
      simultaneously measure TEWL in an identical experimental environment with known
      relative humidity and temperature values. TEWL values of seven locations on
      healthy volunteers were measured simultaneously with each instrument in the same
      room according to the guidelines of the standardization group of the European
      society of contact dermatitis. RESULTS: For TEWL values of all forearm locations,
      there was no statistically significant difference between the mean values
      measured by all three instruments. For TEWL values of forehead locations, there
      was a significant difference between the mean values of open chamber device and
      closed chamber device. For the forehead, values from closed chamber device were
      higher than the open one. CONCLUSION: The TEWL values measured by all instruments
      were constant with small standard deviations. These instruments appear
      sufficiently robust that a standardization group could document similarities and
      differences with in vitro models. We suspect that both techniques will continue
      to be used and that the closed method will find increasing use because of its
      ease of use.

PMID- 15998334
TI  - Objective evaluation of the efficacy of daily topical applications of cosmetics
      bases using the hairless mouse model of atopic dermatitis.
AB  - BACKGROUND/AIMS: Dry skin (xerosis) is a characteristic change associated with
      atopic dermatitis (AD) and has often been treated with topical petrolatum
      applications despite its unfavorable feel. Recently, various therapeutically
      effective skin-care products with better feel have been introduced. To elucidate
      the mechanisms underlying the clinical effectiveness of these newer treatments,
      we used our recently established hairless mouse model of AD. METHODS: We produced
      AD-like skin lesions in hairless mice with repeated applications of 2,4,6
      trinitro-1-chrolobenzene (TNCB) in acetone for 36 days as reported previously.
      Groups of five mice with AD-like skin were treated once daily with an emollient
      type cream containing petrolatum, a moisturizer-type cream containing 10%
      glycerin, a solution of 0.01% dexamethasone in acetone, or were left untreated.
      Over the duration of these treatments, we conducted non-invasive measurements of
      skin surface condition with biophysical instruments and electron microscopic
      evaluation of the surface area size and density of rear surface villi of
      superficial corneocytes. We also obtained skin biopsy samples and blood samples
      at each time point for histopathological evaluation and to assess serum IgE
      levels, respectively. RESULTS: After cessation of topical TNCB applications, AD
      like skin underwent spontaneous resolution with normalization of skin appearance.
      A similar reduction in skin fold thickness was observed in the cream-treated mice
      and in the untreated mouse group, whereas a significant decrease in skin
      thickness was observed in the dexamethasone-treated mice. Transepidermal water
      loss, a measure of stratum corneum barrier function, rapidly normalized in all
      groups, without any statistical differences noted among groups. In comparison
      with untreated skin, skin surface hydration markedly improved after repeated
      applications of the moisturizer-type cream, whereas it consistently remained low
      in dexamethasone-treated skin. The skin treated with emollient-type cream
      appeared similar to skin that received no treatment. Reduced corneocyte surface
      area size resulting from repeated applications of TNCB returned to control size
      with cream treatments, while the corneocyte surface area size became much larger
      following dexamethasone treatment. In addition, the density of villi on the rear
      surface of corneocytes decreased with application of the creams or dexamethasone.
      By contrast, no changes were observed in the number of leukocytes in the
      epidermis or in serum IgE levels among the different treatment groups. In all
      treatment groups, even after 32 days of treatment, reapplication of TNCB resulted
      in early-stage skin swelling, but only in the steroid-treated animals did this
      swelling show a remarkably prolonged time course. CONCLUSIONS: Our present
      results indicate that the efficacy of skin-care products containing no active
      ingredients in treating atopic xerosis can be objectively evaluated using the
      hairless mouse model of AD.

PMID- 15998335
TI  - Contact dermatitis to quinoline, corticosteroids and antibiotics after short time
      treatment of delayed wound healing following malignant melanoma excision in a
      young woman.
AB  - BACKGROUND: We describe a 20-year old woman with retarded healing after a
      melanoma excision. After short time application of several creams containing
      antiseptic, antibiotic and anti-inflammatory ingredients she developed a severe
      contact dermatitis. Patch testing revealed sensitizations against
      corticosteroids, an antibiotic and quinoline. CONCLUSION: In our case multiple
      relevant contact sensitizations appeared within a short period of two months
      after excision of a malignant tumour.

PMID- 15998336
TI  - Tissue adaptation to mechanical forces in healthy, injured and aging tissues.

PMID- 15998337
TI  - Growth hormone and connective tissue in exercise.
AB  - Over the last few years, growth hormone (GH) has become increasingly popular as
      doping within different sports. However, the precise mechanisms behind the
      ergogenic (performance enhancing) effects of GH in athletes are still being
      debated. Besides a well-documented stimulatory effect of GH on carbohydrate and
      fatty acid metabolism, and a possible anabolic effect on myofibrillar muscle
      protein, we suggest a role for GH as an anabolic agent in connective tissue in
      human skeletal muscle and tendon. Given the importance of the connective tissue
      for the function of skeletal muscle and tendon, a strengthening effect of GH on
      connective tissue could fit with the ergogenic effect of GH experienced by
      athletes. This review examines the endogenous secretion of GH and its mediators
      in relation to exercise. Furthermore, we consider the effect of endogenous GH and
      administered recombinant human GH (rhGH) on both myofibrillar and connective
      tissue protein synthesis, thus offering an alternative explanation for the
      ergogenic effect of GH. Finally, we suggest a possible therapeutic role for rhGH
      in clinical management of the frequently suffered injuries in the connective
      tissue.

PMID- 15998338
TI  - The role of vasculature and angiogenesis for the pathogenesis of degenerative
      tendons disease.
AB  - More than 100 years ago Wilhelm Roux (1895) introduced the term "functional
      adaptation to anatomy and physiology". Compared with other organ systems the
      functional adaptation processes are best identifiable in the locomotor system,
      like for example in the two types of tendons: traction and gliding tendons.
      Traction tendons are tendons where the direction of pull is in line with the
      direction of the muscle (e.g. Achilles tendon). Gliding tendons (e.g. tibialis
      posterior tendon) change direction by turning around a bony or fibrous
      hypomochlion. In this region the tendon is subjected to intermittent compressive
      and shear forces and the extracellular matrix consists of avascular
      fibrocartilage. Avascularity is considered to be a key factor for the etiology of
      degenerative tendon disease. The repair capability after repetitive microtrauma
      is strongly compromised in avascular tissue of gliding tendons. Reduced
      vascularity is not a specific feature of gliding tendons; several studies have
      shown that the number and size of blood vessels are largely shortened in the
      waist of the Achilles tendon. However, histological biopsies from degenerated
      Achilles tendons and Doppler flow examinations revealed a high blood vessel
      density in patients with degenerative tendon disease. Angiogenesis is mediated by
      angiogenic factors and recent studies have shown that the vascular endothelial
      growth factor (VEGF) is highly expressed in degenerative Achilles tendons,
      whereas VEGF expression is nearly completely downregulated in healthy tendons.
      Several factors are able to upregulate VEGF expression in tenocytes: hypoxia,
      inflammatory cytokines and mechanical load. Since VEGF has the potential to
      stimulate the expression of matrix metalloproteinases and inhibit the expression
      of tissue inhibitors of matrix metalloproteinases tissue inhibitor of
      metalloproteinases (TIMP) in various cell types (e.g. endothelial cells,
      fibroblasts, chondrocytes), this cytokine might play a significant role for the
      pathogenetic processes during degenerative tendon disease. An animal experiment
      in the rabbit has shown that local injection of VEGF reduced the material
      properties of the Achilles tendon. These experimental findings are in accordance
      with clinical results that a locally administered (in the area with
      neovascularization) sclerosing drug (Polidocanol) has a beneficial effect on
      chronic mid-portion Achilles tendinosis. In conclusion, decreased and increased
      vascularity might be involved in the pathogenesis of degenerative Achilles tendon
      disease.

PMID- 15998339
TI  - Mechanical signals regulating extracellular matrix gene expression in
      fibroblasts.
AB  - Mechanical forces are essential for connective tissue homeostasis. The
      extracellular matrix (ECM) plays a key role in the transmission of forces
      generated by the organism (e.g. muscle contraction) and externally applied (e.g.
      gravity). The expression of specific ECM proteins such as collagens and tenascin
      C, as well as of matrix metalloproteinases, involved in their turnover, is
      influenced by mechanical stimuli. The precise mechanisms by which mechanical
      strains are translated into chemical signals and lead to differential gene
      expression are however not fully understood. Cell-matrix adhesion sites are good
      candidates for hosting a "mechanosensory switch", as they transmit forces from
      the ECM to the cytoskeleton and vice versa by physically linking the cytoskeleton
      to the ECM. Integrins, transmembrane proteins located to these adhesion sites,
      have been shown to trigger a set of internal signaling cascades after mechanical
      stimulation. We have shown that the expression level of tenascin-C directly
      correlates with externally applied mechanical stress, as well as with RhoA/RhoA
      dependent kinase-mediated cytoskeletal tension. Presumably other genes are
      regulated in a similar manner. The changes in ECM composition and mechanical
      properties derived from mechanical stress are relevant in medical intervention
      after ligament and tendon injury.

PMID- 15998340
TI  - Enzymic and non-enzymic cross-linking mechanisms in relation to turnover of
      collagen: relevance to aging and exercise.
AB  - The molecular mechanisms involved in the aging of collagen and consequent
      increase in mechanical strength and stiffness occur in a series of enzymic and
      non-enzymic intermolecular cross-links. The enzymic mechanism involves divalent
      aldimine intermolecular cross-links derived from the reaction of aldehydes which
      then mature to trivalent cross-links and further stabilize the collagen fiber and
      is now well known. Recent studies have demonstrated that the rate of turnover and
      level of telopeptide lysyl hydroxylation modifies the nature of the cross-link
      and hence the mechanical strength of the fiber. The slow turnover of mature
      collagen subsequently allows accumulation of the products of the adventitious non
      enzymic reaction of glucose with the lysines in the triple helix to form glucosyl
      lysine and its Amadori product, that is, the Maillard reaction. These products
      are subsequently oxidized to a complex series of advanced glycation end-products,
      some of which are intermolecular cross-links between the triple helices rendering
      the fiber too stiff for optimal functioning of the collagen fibers, and
      consequently of the particular tissue involved. The glycation reactions following
      maturation are true aging processes, and attempts at their specific inhibition
      involve competitive inhibition of the Maillard reaction and chemical cleavage of
      the glycation cross-links. It is clear that the nature of the age-related cross
      links and hence tissue strength depends on the rate of turnover of the collagen.
      An examination of the particular effect of strenuous exercise on the rate of
      turnover of collagen and hence cross-linking in different tissues could lead to a
      better understanding of optimal sports training regimes.

PMID- 15998341
TI  - Gene expression and matrix turnover in overused and damaged tendons.
AB  - Chronic, painful conditions affecting tendons, frequently known as tendinopathy,
      are very common types of sporting injury. The tendon extracellular matrix is
      substantially altered in tendinopathy, and these changes are thought to precede
      and underlie the clinical condition. The tendon cell response to repeated minor
      injuries or "overuse" is thought to be a major factor in the development of
      tendinopathy. Changes in matrix turnover may also be effected by the cellular
      response to physical load, altering the balance of matrix turnover and changing
      the structure and composition of the tendon. Matrix turnover is relatively high
      in tendons exposed to high mechanical demands, such as the supraspinatus and
      Achilles, and this is thought to represent either a repair or tissue maintenance
      function. Metalloproteinases are a large family of enzymes capable of degrading
      all of the tendon matrix components, and these are thought to play a major role
      in the degradation of matrix during development, adaptation and repair. It is
      proposed that some metalloproteinase enzymes are required for the health of the
      tendon, and others may be damaging, leading to degeneration of the tissue.
      Further research is required to investigate how these enzyme activities are
      regulated in tendon and altered in tendinopathy. A profile of all the
      metalloproteinases expressed and active in healthy and degenerate tendon is
      required and may lead to the development of new drug therapies for these common
      and debilitating sports injuries.

PMID- 15998342
TI  - The chronic painful Achilles and patellar tendon: research on basic biology and
      treatment.
AB  - The etiology and pathogenesis of chronic tendon pain are unknown. Even though
      tendon biopsies having shown an absence of inflammatory cell infiltration, anti
      inflammatory agents (non-steroidal anti-inflammatory drugs, corticosteroidal
      injections) are commonly used. We have demonstrated that it is possible to use
      intratendinous microdialysis to investigate human tendons, and found normal
      prostaglandin E2 (PGE2) levels in chronic painful tendinosis (Achilles and
      patellar) tendons. Furthermore, gene technological analyses of biopsies showed no
      upregulation of pro-inflammatory cytokines. These findings show that there is no
      PGE2-mediated intratendinous inflammation in the chronic stage of these
      conditions. The neurotransmitter glutamate (a potent modulator of pain in the
      central nervous system) was, for the first time, found in human tendons.
      Microdialysis showed significantly higher glutamate levels in chronic painful
      tendinosis (Achilles and patellar) tendons, compared with pain-free normal
      control tendons. The importance of this finding is under evaluation. Treatment is
      considered to be difficult, and not seldom, surgery is needed. However, recent
      researches on non-surgical methods have shown promising clinical results. Painful
      eccentric calf-muscle training has been demonstrated to give good clinical short-
      and mid-term results on patients with chronic painful mid-portion Achilles
      tendinosis. Good clinical results were associated with decreased tendon thickness
      and a structurally more normal tendon with no remaining neovessels. Using
      ultrasonography (US)+color Doppler (CD), and immunhistochemical analyses of
      biopsies, we have recently demonstrated a vasculo/neural (Substance-P and
      Calcitonin Gene-Related Peptide nerves) ingrowth in the chronic painful
      tendinosis tendon, but not in the pain-free normal tendon. A specially designed
      treatment, using US- and CD-guided injections of the sclerosing agent
      Polidocanol, targeting the neovessels outside the tendon, has been shown to cure
      tendon pain in pilot studies, in a majority of the patients. A recent,
      randomized, double-blind study verified the importance of injecting the
      sclerosing substance Polidocanol.

PMID- 15998343
TI  - CDMP-2 injection improves early tendon healing in a rabbit model for surgical
      repair.
AB  - This study examines the hypothesis that cartilage-derived morphogenic protein-2
      (CDMP-2) can improve tendon healing after surgical repair. We have previously
      found improved tendon healing by applying CDMP-2 in models for conservative
      treatment with mechanically loaded Achilles tendon defects in rats and rabbits.
      In this study, the patellar tendon was unloaded by patello- tibial cerclage and
      cut transversely in 40 rabbits. Two hours post-operative, the rabbits received a
      dose of 20 microg of CDMP-2 or vehicle injected into the hematoma. Specimens were
      harvested after 14 and 28 days and evaluated by biomechanical testing,
      radiography and histology. At 14 days, CDMP-2 caused a 65% increase in force at
      failure, a 50% increase in ultimate stress and a 57% increase in stiffness, as
      compared with controls. There was no effect on callus size. At 28 days, no
      differences between the treatment groups could be demonstrated. No bone or
      cartilage was found in any tendon or regenerated tissue at any time point. Thus,
      early tendon repair can be stimulated by CDMP-2 in an unloaded model. These
      results suggest that CDMP-2 might be of interest for clinical use as a complement
      to surgical treatment of tendon ruptures.

PMID- 15998345
TI  - On practices of 'good doctoring': reconsidering the relationship between provider
      roles and patient adherence.
AB  - Questions pertaining to patient adherence and provider roles are part of the
      classical repertoires in sociological and health services research. While
      extensive research programmes consider why patients do not follow medical advice,
      less is known about how practitioners assess patient adherence. Similarly, there
      has been much work on provider roles changing with the organisation of
      healthcare, but less attention to the ways providers conceptualise, choose and
      strategically enact practices in the course of their work. Using data from a year
      long ethnographic study of two diabetes clinics, I examine some of the stances
      medical practitioners actively choose and enact in their treatment of diabetes
      patients - educators, detectives, negotiators, salesmen, cheerleaders and
      policemen - and how they tailor their actions to specific patients in order to
      maximise their adherence to treatment regimens. Findings suggest that the notions
      of 'patient adherence' and 'physician roles' are conceptually broader and more
      fluid than what is captured in existing literature, and this rigidity potentially
      impairs our ability to learn more about the everyday practices of medical work.

PMID- 15998346
TI  - Lay discourses and beliefs related to food risks: an Australian perspective.
AB  - Much publicity has been given to risks associated with food in Western countries.
      This article draws on an Australian research study using qualitative interviews
      to investigate discourses and beliefs related to food risks among lay people. It
      was found that the interviewees were most concerned about dietary fat as a risky
      substance related to overweight, both because of health reasons and physical
      appearance. A secondary concern they identified was the processing of foodstuffs
      and 'unnatural' additives. The dominant discourses which were commonly used to
      organise people's ideas included those concerning 'trying' to consume the 'right'
      kinds of foods, the importance of 'balance', the notion of food as 'functional'
      for bodily health, the 'blame' that often accompanied moral judgements about the
      diet of people with serious illnesses such as cancer and the 'battle' and need
      for 'control' that people with children referred to in relation to making sure
      that their children consumed a healthy diet. Most people were willing to invest
      their trust in government bodies and health professionals to provide accurate
      information about food risks, as well as trusting their own judgement. The
      relevance of the Australian cultural context for these findings is discussed.

PMID- 15998347
TI  - 'He hath the French pox': stigma, social value and social exclusion.
AB  - Goods and resources are finite, and social forces heavily pattern their
      distribution. One of the principal mechanisms for shaping the distribution of
      resources is by regulating entitlement to community membership itself. By
      restricting groups' membership of community, so access to social goods and
      resources diminishes, which in turn has a negative impact on the health and
      wellbeing of the excluded groups. It is argued here that community membership is
      determined on the basis of the perceived social value of groups and individuals
      and stigmatisation is the marking of individuals and groups who are 'unworthy' of
      social investment. Using the notion of reciprocity we show how groups may be
      stigmatised and socially excluded as a mechanism for protecting limited social
      resources from exploitation. This perspective provides an empirically testable
      framework for the understanding of stigma and social exclusion that goes beyond
      the largely descriptive work that currently populates the field. We illustrate
      the process of stigmatisation and social exclusion and discuss how this suggests
      new styles of intervention, as well as new directions for research.

PMID- 15998348
TI  - The demise of repetitive strain injury in sceptical governing rationalities of
      workplace managers.
AB  - In the mid-1990s, RSI (repetitive strain injury) loomed as an occupational health
      epidemic in industrialised countries. A decade later, the problem appears to have
      faded away, but there has been little explanation for how this problem might have
      diminished. This paper offers an explanation for the decline of RSI in the social
      relations of workplaces, in the pragmatic, day-to-day governance of occupational
      health by workplace managers. Using the conceptual lens of governmentality
      theory, this study examined how workplace managers conceptualised, rationalised
      and responded to RSI in their work organisations. Open-ended interviews were
      conducted with 35 managers at four Ontario newspaper workplaces. This paper
      describes managers as guided by a discourse of scepticism about the legitimacy of
      RSI complaints. This discourse was 'practised' in different ways at each
      newspaper in varied RSI-management strategies, but each strategy privileged ideas
      about RSI being problematic in certain types of workers rather than in types of
      physical work environments. This conceptualisation of RSI splintered,
      subordinated and collapsed the problem within a broad human resources framework.
      This paper suggests that the 'taming' of RSI might have occurred in the context
      of micro-political, workplace-level shifts in the conceptualisation and
      management of RSI as an occupational health problem.

PMID- 15998349
TI  - New directions for critical internet health studies: representing cancer
      experience on the web.
AB  - Studies of health representations on the internet have been preoccupied with the
      assessment of their (medically-defined) accuracy and quality. This contrasts with
      studies of health representations in 'old' media, where critical sociological
      analyses are common. Medical sociologists have been concerned to establish the
      potential of web information in transforming professional-client relations. A
      case study of breast and prostate cancer web sites provides evidence of the
      increasing convergence of the 'new' medium of the internet and old media such as
      newspapers and television. Large institutions are now consolidating their
      presence on the web so that users experience increasingly similar messages across
      media platforms. Search engines and links to the web from old media sources
      direct people to heavily resourced, mainstream health sites where, in the case of
      cancer, representations of gender are strikingly similar to those found in
      studies of old media sources. The media convergence thesis contrasts with earlier
      celebrations of the internet as a new medium that would promote a diversity of
      perspectives on health. Using existing methods for analysing media texts and
      developing new methods where appropriate, sociologists and media analysts
      interested in health need to develop more critical perspectives on this important
      new medium.

PMID- 15998351
TI  - How palatable food disrupts appetite regulation.
AB  - Appetite regulation is part of a feedback system that controls the energy
      balance, involving a complex interplay of hunger and satiety signals, produced in
      the hypothalamus as well as in peripheral organs. Hunger signals may be generated
      in peripheral organs (e.g. ghrelin) but most of them are expressed in the
      hypothalamus (neuropeptide Y, orexins, agouti-related peptide, melanin
      concentrating hormone, endogenous opiates and dopamine) and are expressed during
      situations of energy deficiency. Some satiety signals, such as cholecystokinin,
      glucagon-like peptide 1, peptide YY and enterostatin are released from the
      digestive tract in response to food intake. Others, such as leptin and insulin,
      are mobilized in response to perturbations in the nutritional state. Still others
      are generated in neurones of the hypothalamus (alpha-melanocyte-stimulating
      hormone and serotonin). Satiety signals act by inhibiting the expression of
      hunger signals and/or by blunting their effect. Palatable food, i.e. food rich in
      fat and sugar, up-regulates the expression of hunger signals and satiety signals,
      at the same time blunting the response to satiety signals and activating the
      reward system. Hence, palatable food offsets normal appetite regulation, which
      may explain the increasing problem of obesity worldwide.

PMID- 15998352
TI  - Activity of NADPH-cytochrome P-450 reductase of the human heart, liver and lungs
      in the presence of (-)-epigallocatechin gallate, quercetin and resveratrol: an in
      vitro study.
AB  - NADPH-cytochrome P-450 reductase (P-450 reductase) plays a crucial role in the
      metabolism of many endogenic compounds and xenobiotics detoxication. The enzyme
      is also involved in the toxicity of some clinically important antitumour drugs
      (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their
      more toxic metabolites via one electron reduction which triggers free radical
      cascade. In some cases however, such transformation is essential to produce
      therapeutic effect in anticancer drugs. The main purpose of the paper was to
      evaluate the effect of three natural compounds found in human diet: (-)
      epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase
      activity. The activity of the enzyme was determined spectrophotometrically by
      measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using
      human heart, liver and lung microsomes. It was found that quercetin increased the
      P-450 reductase activity in human organs at all tested doses. The activity of
      microcosms in all organs was enhanced according to the concentrations of
      quercetin, which increased the activity in the order lung>heart>liver. Addition
      of EGCG to the reaction mixture enhanced the P-450 reductase activity in the
      following order: liver>heart>lung. However, no significant effect of resveratrol
      on P-450 reductase activity was observed. It seems that the presence of quercetin
      and EGCG in the diet may increase P-450 reductase activity during doxorubicin
      therapy with subsequent increased risk of toxicity. A beneficial effect may be
      obtained in anticancer therapy with bioreductive agents like tirapazamine.

PMID- 15998353
TI  - Vasodilator effect of endothelin in cutaneous microcirculation of heart failure
      patients.
AB  - The heart failure syndrome is associated with a reduced vasodilatory capacity in
      cutaneous microvessels. The aim of this study was to investigate the hypothesis
      that an altered activity of the endothelin system contributes to this reduction.
      The skin blood flow was recorded by laser Doppler flowmetry in patients with
      congestive heart failure and in age- and gender-matched controls without clinical
      signs of heart failure. The vessels were stimulated by iontophoretic
      administration of endothelin-1. The involvement of the endothelin(A) receptor was
      studied by co-administration of a specific antagonist; the role of the
      endothelin(B) receptor was studied by the administration of the selective agonist
      sarafotoxin 6c. The plasma levels of endothelin-1, C-reactive peptide and N
      terminal-pro-Brain Natriuretic Peptide were elevated in heart failure patients.
      Unexpected, endothelin-1 induced an endothelin(A) mediated vasodilation. In the
      heart failure group the dilation was reduced to less than half as compared to
      control. The response to local warming was reduced in parallel indicating that
      the attenuation of the response in the heart failure group can be explained by
      the general decline in vascular reactivity. The response to endothelin(B)
      receptor stimulation did not differ between the groups. The reduction in
      endothelin-1 responsiveness is paralleled by a general reduction in microvascular
      vasodilatory capacity, a phenomenon of increased vascular stiffness in the of
      heart failure subjects.

PMID- 15998354
TI  - Effects of different doses of adrenocorticotrophic hormone on the serum
      lipoprotein profile in healthy subjects.
AB  - Adrenocorticotrophic hormone (ACTH) at pharmacological dosage has marked lipid
      lowering effects that may have therapeutic implications. The rationale behind the
      present investigation was the possible use of ACTH as a lipid-lowering
      replacement for steroids. Thirty-two healthy individuals were randomly divided
      into four groups of 8 each. Three ACTH groups received different doses of ACTH(1
      24) intramuscularly (0.1 mg, 0.5 mg and 1.0 mg daily for four days) and the
      control group received NaCl 0.9% 1 ml intramuscularly daily for four days.
      Moreover, 8 healthy subjects were given ACTH(1-24) 1.0 mg intramuscularly five
      times at an interval of four days. Blood and urine samples were collected at
      regular intervals. ACTH treatment at the dose of 1.0 mg daily lowered the serum
      concentrations of low density lipoprotein (LDL) cholesterol and apolipoprotein B
      by 28% and 22%, respectively, which is similar to previous observations. ACTH
      treatment at the doses of 0.5 mg and 0.1 mg gave smaller reductions (17% and 12%,
      and 9% and 8%, respectively) resulting in near linear dose-response
      relationships. There were no changes in the control group. Only the ACTH dose of
      1.0 mg resulted in significant changes when compared with the control group.
      During the ACTH administration at four-days intervals, the serum concentrations
      of LDL cholesterol and apolipoprotein B reached the lowest values at 48 hr after
      an injection, remained there at 72 hr but were rising again at 96 hr. For
      effective lipid reduction, an ACTH dose of about 1 mg is needed and it should be
      given more often than every fourth day, probably every second or third day. With
      regard to the cortisol exposure, the results should be viewed in the light of
      calculations, presented in the paper, that 1 mg of ACTH is equivalent to 90 mg of
      cortisol administered parenterally.

PMID- 15998355
TI  - Protective effects of L-arginine against cisplatin-induced renal oxidative stress
      and toxicity: role of nitric oxide.
AB  - Nephrotoxicity is a dose-limiting factor in clinical use of cisplatin. The
      changes in renal haemodynamics were suggested to play a role in cisplatin-induced
      nephrotoxicity. The aim of the present study was to investigate the effect of
      modulation of nitric oxide on the severity of cisplatin-induced nephrotoxicity
      using an experimental rat model. A nitric oxide precursor, L-arginine and an
      inhibitor of nitric oxide synthase, L-NAME were used. After six days of cisplatin
      injection, acute nephrotoxicity was demonstrated by a marked increase in serum
      creatinine and blood urea nitrogen. Histological examination of the kidneys
      confirmed the occurrence of renal damage. Moreover, cisplatin induced an increase
      in the level of lipid peroxides and oxidized glutathione and a depletion of
      reduced glutathione. The activities of the antioxidant enzymes glutathione
      peroxidase and superoxide dismutase were also lowered. Besides, there was a
      reduction in the kidney total nitrate/nitrite levels. L-arginine significantly
      attenuated the oxidative stress and nephrotoxic effect of cisplatin. On the other
      hand, L-NAME was found to aggravate cisplatin nephrotoxicity. In conclusion, the
      decrease in the kidney nitric oxide level contributes, at least in part, in the
      mechanism underlying the nephrotoxicity of cisplatin. Furthermore, L-arginine
      shows nephroprotective effects and might be useful in improving the therapeutic
      index of cisplatin.

PMID- 15998356
TI  - Microcrystalline chitosan is ineffective to decrease plasma lipids in both
      apolipoprotein E epsilon 4 carriers and non-carriers: a long-term placebo
      controlled trial in hypercholesterolaemic volunteers.
AB  - Chitosan is a deacetylated product of chitin. Microcrystalline form of chitosan
      has a large adsorption area claimed to decrease gastrointestinal absorption of
      cholesterol. However, the long-term effect of chitosan on plasma lipids is
      variable, the averaged influence being negligible or lacking in mildly-to
      moderately hypercholesterolaemic (4.8-6.8 mmol/l) subjects. We evaluated whether
      this variation and inefficacy depend on apolipoprotein E genotype. 130 middle
      aged, otherwise healthy men (n=55) and women (n=75) were randomized into two
      treatment groups for a 7 month trial. During a 1 month run-in period all
      participants received placebo. Subsequently, one half first took placebo twice
      daily for 3 months and then 1.2 g chitosan twice daily for 3 months, and the
      other half vice versa in a cross-over way. Altogether 84 participants completed
      the study. Plasma lipids and glucose were determined at the end of each phase of
      the study, and all subjects undergone to the cross-over phases were
      apolipoprotein E genotyped. Chitosan altered plasma total, low- and high density
      cholesterol, triglycerides, and blood glucose in neither apolipoprotein E epsilon
      4 allele carriers (n=29) nor non-carriers (n=55), compared to placebo. In
      conclusions, chitosan is ineffective to decrease plasma lipids in apolipoprotein
      E epsilon 4 carrier and non-carrier phenotypes with mildly-to-moderately
      increased plasma cholesterol.

PMID- 15998357
TI  - Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors (statins) as inhibitors of cytochrome P450 2C8.
AB  - Statins are involved in different types of drug interactions. Our objective was
      to study the effect of statins on cytochrome P450 (CYP) 2C8-mediated paclitaxel 6
      alpha-hydroxylation by incubating paclitaxel and statins (0--100 microM) with
      pooled human liver microsomes. Simvastatin, lovastatin, atorvastatin and
      fluvastatin were the most potent inhibitors of CYP2C8 activity with K(i) (IC(50))
      values of 7.1 (9.6) muM, 8.4 (15) microM, 16 (38) microM and 19 (37) microM,
      respectively. Cerivastatin, simvastatin acid and lovastatin acid were less potent
      inhibitors with K(i) (IC(50)) values ranging from 32 to 55 (30--67) microM.
      Rosuvastatin and pravastatin showed no appreciable effect on CYP2C8 activity even
      at 100 microM. In conclusion, all the statins tested, except rosuvastatin and
      pravastatin, had a significant inhibitory effect on the activity of CYP2C8 in
      vitro. Because many of the statins accumulate in the liver and because also their
      metabolites may inhibit CYP2C8 activity, in vivo studies are needed to
      investigate a possible interaction of simvastatin, lovastatin, atorvastatin and
      fluvastatin with CYP2C8 substrate drugs.

PMID- 15998358
TI  - Involvement of different calcium channels in the depolarization-evoked release of
      noradrenaline from sympathetic neurones in rabbit carotid artery.
AB  - The calcium channels coupled to noradrenaline release from sympathetic neurones
      in the rabbit isolated carotid artery were examined. Rings of carotid artery were
      preloaded with (-)-[(3)H]noradrenaline and the fractional (3)H overflow evoked by
      electrical-field stimulation was determined by liquid scintillation spectrometry.
      The N-type Ca(2+) channel blocking agent omega-conotoxin GVIA (3x10(-9)-6x10(-8)
      M) reduced the stimulation-evoked (3)H overflow. The maximal inhibition was seen
      with 3x10(-8) M. The maximal reduction was more marked at a low (2 Hz)
      stimulation frequency than at a high one (30 Hz). Mibefradil (10(-6) M)
      irreversibly reduced the (3)H overflow evoked by field stimulation (2 Hz). At 30
      Hz, the reduction was more marked than at 2 Hz. Mibefradil (3x10(-6)-10(-5) M)
      enhanced the passive (3)H outflow. The reduction of the stimulation (30 Hz)
      evoked (3)H overflow seen with omega-conotoxin GVIA (3x10(-8) M) was enhanced by
      mibefradil (10(-6) M) and unaffected by nimodipine (10(-5) M) and omega-agatoxin
      IVA (10(-8) M). We conclude that the stimulation-evoked release of noradrenaline
      from sympathetic neurones in rabbit carotid artery at a low frequency (2 Hz) is
      mediated mainly by the N-type calcium channels. At a high frequency (30 Hz), T
      type Ca(2+) channels are also involved.

PMID- 15998359
TI  - Porcine CYP2A polymorphisms and activity.
AB  - CYP2A6 in man catalyzes the oxidation of nicotine-forming cotinine and 7
      hydroxylation of coumarin, which is used as test substrate for CYP2A6 in man.
      Large interindividual differences are found in man and some are due to genetic
      polymorphism. The 7-hydroxylation of coumarin is present in pigs, and an inter
      individual variation has been found that might be due to polymorphisms. To enable
      the finding of polymorphism in pigs, the minipig cDNA was sequenced. Two cDNAs
      were found and translated to a 494 and a 487 amino acid long protein, both cDNAs
      were found in all but one pig. The 494 a.a. protein showed high homology to the
      human and 100% homology to the conventional pig CYP2A19 protein. In the wild type
      protein, all 6 substrate recognition sites were found, whereas the short protein
      only contained the first 5 substrate recognition sites. SSCP analysis revealed 3
      polymorphisms. In order to study the effect of these polymorphisms on enzyme
      activity, microsomes were incubated with nicotine and coumarin. The polymorphisms
      appeared to have no effect on either enzyme activity as the specific enzyme
      activity towards nicotine and coumarin were approximately the same for all pigs.
      The specificity of pig CYP2A was investigated and it was found that the formation
      of cotinine correlated with the immunochemical level of CYP2A as did the coumarin
      hydroxylation. Anti-human CYP2A inhibitory antibody inhibited coumarin 7
      hydroxylation by about 90% and formation of cotinine by 44--60% and 85--100% at
      substrate concentrations of 500 microM and 50 microM respectively, showing that
      coumarin and nicotine (50 microM) are very specific substrates for CYP2A in pigs,
      whereas the CYP2A only is responsible for about 50% of the cotinine formation at
      a 500 microM nicotine incubation concentration. These results show that the large
      interindividual differences in porcine CYP2A activity are not caused by
      polymorphisms but transcriptional regulation and the coumarin 7-hydroxylation is
      as specific a reaction for porcine CYP2A as for human CYP2A6.

PMID- 15998360
TI  - Influence of a Mexican diet on the bioavailability of albendazole.

PMID- 15998361
TI  - Performance of a mixed Lagrange time delay estimation autoregressive (MLTDEAR)
      model for single-image signal- to-noise ratio estimation in scanning electron
      microscopy.
AB  - A novel technique based on the statistical autoregressive (AR) model has recently
      been developed as a solution to estimate the signal-to-noise ratio (SNR) in
      scanning electron microscope (SEM) images. In another research study, the authors
      also developed an algorithm by cascading the AR model with the Lagrange time
      delay (LTD) estimator. This technique is named the mixed Lagrange time delay
      estimation autoregressive (MLTDEAR) model. In this paper, the fundamental
      performance limits for the problem of single-image SNR estimation as derived from
      the Cramer-Rao inequality is presented. We compared the experimental performances
      of several existing methods--the simple method, the first-order linear
      interpolator, the AR-based estimator as well as the MLTDEAR method--with respect
      to this performance bound. In a few test cases involving different images, the
      efficiency of the MLTDEAR single-image estimation technique proved to be
      significantly better than that of the other three methods. Study of the effect of
      different SEM setting conditions that affect the autocorrelation function curve
      is also discussed.

PMID- 15998362
TI  - A new stereological principle for test lines in three-dimensional space.
AB  - A new principle is presented to generate isotropic uniform random (IUR) test
      lines hitting a geometric structure in three-dimensional space (3D). The
      principle therefore concerns the estimation of surface area, volume, membrane
      thickness, etc., of arbitrary structures with piecewise smooth boundary. The
      principle states that a point-sampled test line on an isotropic plane through a
      fixed point in 3D is effectively an invariant test line in 3D. Particular
      attention is devoted to the stereology of particles, where an alternative to the
      surfactor method is obtained to estimate surface area. An interesting case arises
      when the particle is convex. The methods are illustrated with synthetic examples.

PMID- 15998363
TI  - Electron and ion imaging of gland cells using the FIB/SEM system.
AB  - The FIB/SEM system was satisfactorily used for scanning ion (SIM) and scanning
      electron microscopy (SEM) of gland epithelial cells of a terrestrial isopod
      Porcellio scaber (Isopoda, Crustacea). The interior of cells was exposed by site
      specific in situ focused ion beam (FIB) milling. Scanning ion (SI) imaging was an
      adequate substitution for scanning electron (SE) imaging when charging rendered
      SE imaging impossible. No significant differences in resolution between the SI
      and SE images were observed. The contrast on both the SI and SE images is a
      topographic. The consequences of SI imaging are, among others, introduction of
      Ga(+) ions on/into the samples and destruction of the imaged surface. These two
      characteristics of SI imaging can be used advantageously. Introduction of Ga(+)
      ions onto the specimen neutralizes the charge effect in the subsequent SE
      imaging. In addition, the destructive nature of SI imaging can be used as a tool
      for the gradual removal of the exposed layer of the imaged surface, uncovering
      the structures lying beneath. Alternative SEM and SIM in combination with site
      specific in situ FIB sample sectioning made it possible to image the
      submicrometre structures of gland epithelium cells with reproducibility,
      repeatability and in the same range of magnifications as in transmission electron
      microscopy (TEM). At the present state of technology, ultrastructural elements
      imaged by the FIB/SEM system cannot be directly identified by comparison with TEM
      images.

PMID- 15998364
TI  - Calcification of senile cataractous lens determined by Fourier transform infrared
      (FTIR) and Raman microspectroscopies.
AB  - A calcified plaque on the surface of a senile cataractous lens (CL) isolated from
      a 79-year-old male patient was identified and its chemical composition quantified
      using Fourier transform infrared (FTIR) and confocal Raman microspectroscopies.
      The noncalcified area of the same CL and hydroxyapatite (HA) were selected as a
      control. Several unique absorption bands, at 960, 1034 and 1090 cm(-1) assigned
      to the nu(1) and nu(3) stretching modes of phosphate and at 875 cm(-1) attributed
      to carbonate, were clearly displayed in the infrared (IR) spectra of calcified
      plaque and HA. A peak at 961 cm(-1) due to the nu(1) stretching mode of phosphate
      was also evidenced in the Raman spectra of calcified plaque and HA. The calcified
      plaque formed within the lens protein was found to mainly consist of a mature HA,
      in which type-A carbonate apatites (11.4%), type-B carbonate apatites (55.6%) and
      liable surface carbonate ions (33.0%) were presented. A higher content of the
      liable carbonate implies that the calcification or mineralization in this
      calcified lens was incomplete and still in progress. Moreover, calcification
      seems not to influence the secondary structure of lens protein because both IR
      and Raman spectra for the lens protein in the noncalcified area and calcified
      plaque were similar. The result suggests that both microscopic FTIR and Raman
      spectroscopies were easy to perform and capable of determination of the chemical
      composition of a calcified CL.

PMID- 15998365
TI  - Gene expression profiles of TNF-alpha, TACE, furin, IL-1beta and matrilysin in
      UVA- and UVB-irradiated HaCat cells.
AB  - BACKGROUND/PURPOSE: It is known that solar ultraviolet (UV) irradiation exerts
      multiple effects on mammalian skin tissues, one of which is the induction of
      local and systemic immunosuppression as well as inflammation. Tumor necrosis
      factor-alpha (TNF-alpha) and other cytokines are suggested to play a role in
      these responses. Quantitative real-time polymerase chain reaction (TaqMan RTPCR)
      was used to elucidate the effect of UVA and UVB irradiation on the expression of
      genes coding for TNF-alpha, IL-1beta, IL-10, FasL, matrilysin, TACE and furin in
      HaCaT cells over a 48 h period (IL-1beta, interleukin-1beta; FasL, Fas ligand).
      METHODS: Cultured HaCaT cells were either sham irradiated (control) or exposed to
      UVA (2000 and 8000 J/m2) or UVB (200 and 2000 J/m2) radiation. RNA was extracted
      from cells at 0, 4, 8, 12, 16, 24, 48 h post-irradiation and reverse transcribed
      to generate cDNA for subsequent real-time PCR amplification. RESULTS: Significant
      increases in the mRNA levels for all genes tested were detected in both UVA- and
      UVB-irradiated HaCaT cells compared with control (sham-irradiated) cells. TNF
      alpha mRNA levels were immediately up-regulated (0 h) after irradiation, with
      maximal induction at 8 h post 2000 J/m2 UVA and 200 J/m2 UVB irradiation, at 4 h
      post 8000 J UVA irradiation and at 48 h post 2000 J/m2 UVB irradiation. No
      correlation was observed between TNF-alpha, TACE and furin mRNA induction in the
      different irradiated cohorts. CONCLUSION: Results suggest that time-distinct gene
      induction of TNF-alpha, furin, IL-1beta and matrilysin may be involved in UV
      induced cellular responses, but not for TACE. In general, mRNA induction was dose
      dependent at some time points post-irradiation, but not throughout the whole time
      course tested. Our results show that quantitative real-time PCR is a useful tool
      in the analysis of quantitative changes of mRNA levels in cultured HaCaT cells
      after UV exposure.

PMID- 15998366
TI  - Ultraviolet A exposure might increase metastasis of mouse melanoma: a pilot
      study.
AB  - BACKGROUND: The major sources of long-wave ultraviolet A radiation (UVA; 320-400
      nm) exposure are extensive sunbathing and tanning in solaria. While the
      carcinogenic effects of mid-wave ultraviolet B radiation (UVB; 280-320 nm) are
      well recognized, the potentially hazardous effects of UVA are less understood.
      Several studies have shown that a variety of physiological processes in the cell
      are modified by UVA exposure, some of which might be involved in the regulation
      of tumor metastasis. In this study we suggest that UVA radiation could lead to
      the increase of metastatic capability of melanoma cells in mice. METHOD/RESULT: A
      pilot in vivo study was executed using C57BL/6 mice and syngeneic B16 melanoma
      cell lines. Mice were intravenously (i.v.) injected with either B16-F1 or B16-F10
      melanoma cells into the tail vein and then immediately exposed to UVA. Fourteen
      days after melanoma injection, lungs were collected and the quantity and quality
      of metastases were determined under a dissecting microscope. As an outcome of the
      pilot study we observed that i.v. injected melanoma cells formed more lung
      metastases in the UVA-exposed mice in comparison with the control mice.
      CONCLUSION: This result suggests that the UVA exposure of mice, with melanoma
      cells present in blood circulation, increases the formation of melanoma
      metastases in lungs. Further studies should determine whether a similar pro
      metastatic effect, as observed in mice, could occur in humans and whether other
      than melanoma tumors might be susceptible.

PMID- 15998367
TI  - Sunscreen use and sun protection practices in students and personnel of Celal
      Bayar University.
AB  - BACKGROUND/PURPOSE: The steady increase in the incidence of melanoma, non
      melanoma cutaneous neoplasia and preneoplastic disorders has contributed to the
      demand for more effective protection from the sun. In this study, we aimed to
      determine the prevalence of sunscreen use and other sun protection behaviors in a
      large sample of students and personnel of Celal Bayar University, Manisa, Turkey.
      METHODS: The study group included 1018 participants of whom 607 work in the Celal
      Bayar University Hospital and 411 are students from the Medical Faculty and
      School for Health Professionals. All participants completed a questionnaire
      composed of 45 items about sun protection and other health behaviors, such as
      sports activity, use of cigarettes, alcohol and seat-belts. Sun protection factor
      (SPF) of sunscreen, avoiding sun exposure during peak hours, wearing clothing, a
      hat and sunglasses were studied. RESULTS: Of the 1018, 403 participants were male
      and 615 were female. While avoiding sun exposure during peak hours was the most
      popular preventive behavior for men (42.5%), wearing sunglasses was the most
      popular one for women (50.7%). Avoiding exposure was the second preventive
      behavior for women (42.1%). Use of sunscreen with SPF 15+ was the second popular
      protective measure for men (19.4%) and the third one for women (39.2%). There
      were no significant relationships between sun protection behaviors and obesity,
      use of cigarettes and alcohol. We also investigated behavioral changes with
      sunburn experience in the participants who had sunburn history. Among these
      behavioral changes, increased use of sunscreen and decreased sun exposure during
      peak hours with sunburn experience were significant. CONCLUSION: Our study
      demonstrated that the risk of sun exposure is largely unrecognized in Manisa,
      Turkey, and we have very incomplete information about protective measures. An
      efficient policy of education on the effective use of sun protection methods
      should be developed to prevent skin cancer.

PMID- 15998368
TI  - The effects of heating and cooling on ultraviolet radiation-induced erythema and
      pigmentation in human skin.
AB  - BACKGROUND/PURPOSE: As most biochemical systems are affected by temperature,
      thermal changes before or after ultraviolet (UV) irradiation could influence skin
      vascular blood flow changes and inflammatory responses. In this study, our aim
      was to investigate the influence of thermal changes on UV-induced acute skin
      reactions, namely, erythema and pigmentation. METHODS: Our volunteers consisted
      of 10 males, with ages ranging from 22 to 24 years and with Fitzpatrick's skin
      type III or IV. Skin temperatures were changed with a 45 degrees C heating pad or
      by ice pack application before or after UV irradiation (control, 1 minimal
      erythema dose (MED), 2 MED) and then changes in erythema and pigmentation were
      measured by a Minolta Spectrophotometer CM-2002. RESULTS: The present study
      demonstrates that both heating and cooling increase skin erythema and reduce
      pigmentation, and that the timing of heating and cooling influences the UV
      induced skin reaction. Pre-heating and post-cooling groups showed more UV-induced
      erythema than the post-heating and pre-cooling groups, respectively. CONCLUSION:
      Our results indicate that alteration of skin surface temperature could modulate
      UV-induced erythema and pigmentation responses.

PMID- 15998369
TI  - Biophysical, histological and biochemical changes after non-ablative treatments
      with the 595 and 1320 nm lasers: a comparative study.
AB  - BACKGROUND/PURPOSE: The objective was to compare the efficiencies of the 595 nm
      pulsed dye and the 1320 nm Nd : YAG laser non-ablative rejuvenation. METHODS: KM
      mice were irradiated with the 595 nm pulsed dye and the 1320 nm Nd : YAG lasers.
      Histological changes were evaluated immediately, 1, 7, 21, 30 and 60 days after
      the two laser treatments. Skin hydration and hydroxyproline content were measured
      to quantify the degree of improvement of the skin's water-holding capacity and
      the rate of hydroxyproline synthesis. RESULTS: Although not statistically
      significant, the 1320 nm Nd : YAG laser treatment induced 9.7% greater
      improvement of skin hydration than the 595 nm laser while the 595 nm pulsed dye
      laser treatment led to a thicker dermis and 8.7% greater increase of
      hydroxyproline than the 1320 nm laser. More than 50% increase of collagen type I
      was observed in 75% of 595 nm laser-treated sites and 42% of 1320 nm laser
      treated sites, and more than 25% increase of collagen type III was observed in
      75% of 595 nm laser-treated sites and 50% of 1320 nm laser-treated sites. The 595
      nm laser treatment was better in increasing the amount of collagen fibers,
      especially collagen type I (P < 0.05). CONCLUSION: Our results demonstrated that
      the 595 nm laser appeared to be more effective in increasing new collagen
      formation, while the 1320 nm laser was superior to the 595 nm laser in improving
      the skin's water-holding capacity.

PMID- 15998370
TI  - Soluble tumor necrosis factor alpha receptor type 1 in psoriasis patients treated
      with narrowband ultraviolet B.
AB  - PURPOSE: The purpose of this study was to examine the influence of narrowband
      ultraviolet (NB-UVB) therapy on the serum concentration of soluble tumor necrosis
      factor receptor type 1 (sTNF-R1) in psoriasis patients. METHODS: Twenty-seven
      patients received NB-UVB therapy three to five times a week for 4 weeks. The
      assessment of skin lesions using psoriasis area and severity index (PASI) and
      serum concentration of sTNF-R1 was performed at the baseline, at 2, 4 and 4 weeks
      after treatment cessation. The sera of healthy subject were used as controls.
      RESULTS: The baseline PASI was 13.56 +/- 5.71, sTNF-R1 concentration was 1.89 +/-
      0.43 ng/ml in patients and 1.48 +/- 0.30 ng/ml in controls (P < 0.05). The
      baseline PASI correlated to sTNF-R1 (r = 0.52, P < 0.05). The decline in
      concentrations of sTNF-R1 paralleled the decline of PASI achieved during therapy
      but still exceeded control values. CONCLUSION: The results of the study confirm
      the role of sTNF-R1 as a marker of psoriasis severity and efficacy of treatment.
      They also suggest that NB-UVB influences the serum level of sTNF-R1.

PMID- 15998372
TI  - Extraskeletal myxoid chondrosarcoma: updated clinicopathological and molecular
      genetic characteristics.
AB  - Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma
      characterized by distinctive morphological and cytogenetical features. As its
      name implies, EMC was believed to represent a variant of soft-tissue
      chondrosarcoma owing to its histological resemblance to chondroblastic tissue in
      the early stages of cartilage development or chondroid tumors such as skeletal
      chondrosarcoma. However, the chondroid nature has been a subject of controversy,
      and its line of differentiation remains to be determined. Consequently, the tumor
      is provisionally classified into a group of tumors of uncertain differentiation
      in the revised World Health Organization classification of tumors of soft tissue
      and bone. Moreover, immunohistochemical and ultrastructural features of neural or
      neuroendocrine differentiation have been recently reported in a subset of EMC,
      providing a new insight into their histogenetic nature. Chromosomal
      rearrangements involving 9q22, such as t(9;22)(q22;q12), and resultant NR4A3
      fusion genes are tumor-type specific or pathognomotic for this entity and are
      assumed to play an important role in the development of EMC. Although the
      biological mechanisms and functions are largely unknown, the NR4A3-related
      pathway is considered a potential molecular target for future therapeutic
      intervention. Because of its protracted but resilient nature, a tenacious and
      long-term follow up is necessary for any patient.

PMID- 15998373
TI  - Aberrant expression of pyloric gland-type mucin in mucin-producing bile duct
      carcinomas: a clear difference between the core peptide and the carbohydrate
      moiety.
AB  - The authors have recently defined the clinopathological entity of a mucin
      producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes:
      'columnar-type' and 'cuboidal-type' MPBT. Mucin core protein 6 (MUC6), which is
      present in normal pyloric glands, had higher expression levels in cuboidal-type
      tumors than in columnar-type tumors. In the pyloric glands, a carbohydrate
      antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed.
      In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT,
      expression profiles were evaluated in 38 surgically excised mucin-producing bile
      duct carcinomas (MPBC; cuboidal-type, n = 15; columnar-type, n = 23), using
      immunohistochemistry. The staining rate was graded as follows: -, <5% of
      neoplastic cells stained; +, 5% to <20%; + +, 20% to <50%; + + +, > or =50%. In
      cuboidal-type MPBC, MUC6 was positive in all cases (+ + +, 13/15; + +, 1/15; +,
      1/15), whereas CA/HIK1083 was negative in all cases (-, 15/15; P < 0.0001). In
      columnar-type MPBC, MUC6 was positive in 65% of cases (+ + +, 6/23; + +, 8/23; +,
      1/23; -, 8/23), and CA/HIK1083 was positive in 52% (+ +, 3/23; +, 9/23; -, 11/23;
      not significant). Our results clearly demonstrate that cuboidal-type MPBC have an
      aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083-. This unique
      profile may be related to different outcomes of patients with MPBC.

PMID- 15998374
TI  - Concordant loss of fragile gene expression early in breast cancer development.
AB  - The FHIT and WWOX genes encompass the FRA3B and FRA16D fragile sites at
      chromosomes 3p14.2 and 16q23.3, respectively. Reduced Fhit and Wwox expression
      has been reported in approximately two-thirds of invasive breast tumors.
      Expression of these fragile gene products, as well as ErbB2 and p53, were
      evaluated immunohistochemically in 44 pure and 31 adjacent-to-invasive ductal
      carcinoma in-situ (DCIS) cases. Reduced Fhit and Wwox expression were observed in
      (i) 70% and 68% of pure DCIS; (ii) 52% and 55% of DCIS adjacent-to-invasive tumor
      cases; and (iii) 20% and 50% of adjacent normal tissue in pure DCIS cases.
      Reduced Wwox expression in adjacent normal tissue was observed in 30% of cases in
      the DCIS adjacent-to-invasive group. Reduced Fhit and Wwox expression was
      observed in 61% of adjoining invasive tumors. In all normal, pure DCIS, and DCIS
      adjacent-to-invasive lesions, Fhit and Wwox expression was positively associated
      (P = 0.034, P = 0.042, P = 0.004, respectively) and in the invasive component
      there was a positive trend toward association (P = 0.075). Fhit and Wwox were
      more frequently reduced in high-grade lesions in the DCIS adjacent-to-invasive (P
      = 0.025, P = 0.004, respectively). In the pure DCIS group, there was a
      statistically significant negative association between Fhit and ErbB2 expression
      in DCIS (P = 0.035). In summary, reduced Fhit and Wwox expression in in-situ
      breast cancer was associated, which may contribute to the high-grade DCIS
      invasive tumor pathway.

PMID- 15998375
TI  - KIT expression in normal and neoplastic renal tissues: immunohistochemical and
      molecular genetic analysis.
AB  - Renal chromophobe cell carcinomas (ChCC) and oncocytomas express KIT. This
      character seems to reflect their common histogenesis from distal nephrons. In the
      normal kidney, however, the expression and localization of KIT are unclear. KIT
      expression in angiomyolipoma and congenital mesoblastic nephroma (CMN), is still
      controversial. c-kit mutations are reportedly rare in ChCC, but there is little
      information in other renal neoplasms, and no reported data on mutations of
      platelet-derived growth factor receptor (PDGFR). In order to address these issues
      the authors examined five ChCC, five oncocytomas, seven papillary cell
      carcinomas, two collecting duct carcinomas, 12 angiomyolipomas, and three CMN, as
      well as 10 normal renal tissues. In the normal kidney KIT was specifically
      expressed in the distal nephrons. Nine of 12 (75%) angiomyolipomas contained
      scattered KIT-positive cells, whereas all three CMN were completely negative for
      KIT. The presence of KIT-positive cells in angiomyolipomas was likely to
      correspond to that of melanocytic marker-positive cells, which mainly showed
      epithelioid morphology. Polymerase chain reaction-single-strand conformation
      polymorphism showed no evidence of mutations of c-kit or PDGFR in any of the
      tumors examined.

PMID- 15998376
TI  - Regular expression of osteopontin in granular cell tumor: distinctive feature
      among Schwannian cell tumors.
AB  - For further characterization of S-100 protein-positive granular cell tumor (GCT),
      the expression of osteopontin (OPN) in the tumor cells was compared with other
      types of Schwannian cell tumors. Twenty GCT, three amputation neuromas, 12
      neurilemmomas (NM) and three malignant peripheral nerve sheath tumors (MPNST)
      were used. In addition, two granular cell epulides were employed because of
      histological similarity to that of GCT. Immunohistochemistry by anti-OPN
      monoclonal antibody revealed OPN-immunoreactivity in tumor cells of all GCT and
      stromal macrophages in neurilemmomas and one MPNST, but neither in amputation
      neuromas nor in granular cell epulides. All nine GCT studied by in situ
      hybridization (ISH) and all three GCT analyzed by reverse transcription
      polymerase chain reaction (RT-PCR) were positive for OPN mRNA. In contrast, seven
      NM and three amputation neuromas were negative for OPN mRNA by either ISH or RT
      PCR, while macrophages infiltrated in these tumors had OPN mRNA consistently.
      Double immunostaining for OPN and CD68, a lysosome-associated glycoprotein,
      showed their colocalization in tumor cells of GCT, suggesting a possible
      degradation of OPN by lysosomes. In conclusion, GCT among Schwannian cell tumors
      consistently express OPN, but its biological significance requires further
      investigation.

PMID- 15998377
TI  - Human papillomavirus genotyping by oligonucleotide microarray and p16 expression
      in uterine cervical intraepithelial neoplasm and in invasive carcinoma in Korean
      women.
AB  - For evaluating the diagnostic significance of p16(INK4A) over-expression in the
      uterine cervical intraepithelial neoplasm and in invasive carcinoma, human
      papillomavirus (HPV) was detected and genotyped by oligonucleotide microarray in
      archival tissues of 117 cervical specimens, including 47 invasive squamous cell
      carcinomas (SCC), 30 cases of cervical intraepithelial neoplasia (CIN), 20
      adenocarcinomas, and 20 cases of non-neoplastic cervix. The expression of
      p16(INK4A) protein was immunohistochemically studied in these cases and in five
      HPV-positive and one HPV-negative cervical cancer cell lines. HPV was detected in
      50% of CIN, 61.7% of SCC, and 45.5% of adenocarcinomas. p16(INK4A) expression was
      seen in all 20 cases of adenocarcinoma, 78.7% (37/47) of SCC, and 96.7% (29/30)
      of CIN, but not in any cases of the non-neoplastic cervix. There was no
      difference in p16(INK4A) expression between the HPV-positive and HPV-negative
      cervical lesions. All HPV-positive and -negative cervical cancer cell lines
      expressed p16(INK4A) protein. In conclusion, the presence of p16(INK4A)
      expression in cervical squamous and glandular epithelium indicates the existence
      of dysplasia or malignancy in the uterine cervix, regardless of HPV infection.

PMID- 15998378
TI  - Pulmonary complications of cystic echinococcosis in children in Uruguay.
AB  - Cystic echinococcal lesions surgically removed from 99 patients aged 1-15 years
      in Uruguay were histopathologically studied. The lesions were collected from the
      lungs, liver, peritoneum, omentum, pleura, ovary, appendix and perinephrium. All
      intact cysts were well-developed and unilocular. Pulmonary and hepatic fertile
      cysts in which protoscoleces were produced were in 75% and 47%, respectively, of
      all patients. Fertile cysts having many protoscoleces were in the lungs of a 1
      year-old infant. Sixteen ruptured pulmonary cysts were found in the lungs of 13
      patients and four ruptured hepatic cysts were found in the liver of three
      patients. Pulmonary complications were seen in patients having pulmonary
      echinococcal cysts. In lung tissue surrounding echinococcal cysts, pulmonary
      complications included chronic congestion, hemorrhage, bronchopneumonia, as well
      as interstitial pneumonia that included histological changes caused by
      bronchiolitis, organizing pneumonia and obstructive pneumonia. Liver tissue
      adjacent to echinococcal cysts showed atrophy of hepatic cells, proliferation of
      interstices, small focal hemorrhages, and infiltration of mononuclear cells. The
      present study shows that a close relationship exists between pulmonary
      echinococcosis and pneumonia. The term 'echinococcal pneumonia' is proposed for
      pneumonia accompanying pulmonary echinococcosis.

PMID- 15998379
TI  - Primary bone carcinosarcoma: chondrosarcoma and squamous cell carcinoma with
      keratin pearl formation.
AB  - Malignant bone tumors with epithelial differentiation are extremely rare. Only
      one case of primary malignant bone tumor with distinct squamous cell carcinoma
      and chondrosarcoma has ever been reported. Reported herein is a case of primary
      malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma, so
      called carcinosarcoma of bone, arising in the femur of a 53-year-old man. The
      tumor was located within the femur and was diagnosed by curettage as a well
      differentiated chondrosarcoma. No primary tumor was detected in any other organ.
      Within a few months the tumor had rapidly grown toward the soft tissue, and
      hemipelvectomy was performed. Examination of the surgical specimen revealed that
      the tumor was mainly composed of undifferentiated spindle sarcoma cells with
      scattered foci of chondrosarcoma and of squamous cell carcinoma with keratin
      pearl formation. The patient died approximately 6 months postoperatively. At
      autopsy multiple metastases were detected in the heart, both lungs, muscles, and
      lymph nodes. Interestingly, the chondrosarcoma and squamous cell carcinoma
      components were observed in several metastatic foci. The tumors in both the
      previously reported case and the present case contained components of
      chondrosarcoma and squamous cell carcinoma with keratin pearl formation, and this
      combination of histological features may be a unique characteristic of
      carcinosarcoma of bone.

PMID- 15998380
TI  - Malignant myoepithelioma (myoepithelial carcinoma) of soft tissue.
AB  - Malignant myoepithelioma of soft tissue is extremely rare. Presented herein is a
      case arising in a 17-year-old man. The tumor was initially noticed as a painless
      deep soft-tissue mass in the right forearm when the patient was aged 3 years.
      Thereafter, it grew without remarkable symptoms, such as pain or tenderness,
      until his visit to the hospital because of swelling of his forearm when he was 17
      years old. An excisional biopsy specimen disclosed an invasive tumor exhibiting a
      lobular architecture. The tumor cells were arranged in a reticular and/or
      trabecular fashion with a myxoid background, and nuclear atypia was evident.
      Mitoses and tumor necrosis were also observed. Immunohistochemically, S-100
      protein and epithelial markers were diffusely positive. Faint intercellular
      junctions and basal laminae were identified by electronmicroscopy. On the basis
      of these findings, the tumor was diagnosed as a malignant myoepithelioma of soft
      tissue. Six months later, multiple lung metastases were observed, and an open
      biopsy revealed a neoplasm displaying the same histological feature as the
      previously biopsied specimens. The patient died of his disease 18 months after
      the lung biopsy. Malignant myoepithelioma should be kept in mind in diagnosis of
      deep soft-tissue tumors with epithelioid features.

PMID- 15998382
TI  - Autopsy case of microscopic polyangiitis with crescentic glomerulonephritis and
      necrotizing pancreatitis.
AB  - Herein is reported the case of an 84-year-old woman who initially manifested
      rapidly progressive glomerulonephritis following a urinary tract infection.
      Laboratory findings showed a high titer of myeloperoxidase-antineutrophil
      cytoplasmic antibody (MPO-ANCA). Treatment with high-dose i.v. steroids resulted
      in clinical recovery and an undetectable MPO-ANCA titer. Two months later the
      patient was readmitted in a state of severe shock. Laboratory examination showed
      the deterioration of renal function, leukocytosis, and coagulation abnormalities
      consistent with disseminated intravascular coagulation (DIC). The patient died 12
      days later. The post-mortem examination revealed necrotizing pancreatitis due to
      acute-stage vasculitis typified by fibrinoid necrosis of the arterioles and
      venules, and crescentic glomerulonephritis with healed-stage vasculitis. In the
      lungs, capillaritis with diffuse alveolar hemorrhage was not evident, but
      arteriolitis and phlebitis were occasionally seen. This case represents an
      unusual complication of necrotizing pancreatitis in the setting of microscopic
      polyangiitis. Thus, it is important to consider reactivation independent of the
      titer of ANCA in the course of the disease.

PMID- 15998381
TI  - Intracerebral schwannoma clinically and radiologically mimicking meningioma.
AB  - A case of intracerebral schwannoma (ICS) occurring in a 33-year-old woman is
      presented. The patient's history of headache, numbness, tingling and the recent
      development of weakness of the right upper extremity with right facial droop
      began during pregnancy. Magnetic resonance imaging (MRI) showed a 4 x 2 x 2 cm
      heterogeneous, gadolinium-enhanced mass at the left frontoparietal junction, with
      peritumoral edema and a dural-based attachment. During her pregnancy, the mass
      increased in size. The surgically resected specimen consisted of lobulated,
      somewhat gelatinous soft tissue. Microscopically, the tumor demonstrated classic
      biphasic Antoni type A and B patterns, admixed with degenerative changes.
      Immunohistochemically, the neoplastic cells were positive for S-100 protein
      (diffuse and strong), CD34 (primarily in Antoni B areas), glial fibrillary acidic
      protein (GFAP; weak and diffuse) and calretinin (mainly in Antoni A areas), while
      none was positive for CD31, estrogen and progesterone receptors, bcl-2, or
      epithelial membrane antigen (EMA). Ultrastructurally, basal laminae and Luse
      bodies were identified. The differential diagnosis includes fibrous meningioma,
      solitary fibrous tumor, and ICS. Twenty-seven cases of ICS were reviewed in which
      the histological diagnosis was confirmed immunohistochemically or
      ultrastructually, and the cases were summarized (including the present case). A
      combined use of immunostains (S-100 protein, EMA, CD34, and maybe calretinin) is
      of great help in distinguishing ICS from its histological mimickers.

PMID- 15998383
TI  - Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colon.
AB  - Herein is presented a case of cytokeratin (CK) 20-positive large cell
      neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage
      IV and located in the ascending colon. Pathological examination of the resected
      tumor revealed nested and solid proliferation of large undifferentiated cells
      with vesicular nucleus and prominent nucleoli. No areas showed differentiation
      toward adenocarcinoma or squamous cell carcinoma. Tumor cells were
      immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal),
      and bore electron-dense granules. With these features, the tumor was diagnosed as
      a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local
      recurrence progressed, and the patient died of the primary disease 7 months after
      operation. The autopsy confirmed this diagnosis without detectable tumors in the
      lungs. Interestingly, more than half of the tumor cells were positive for CK 20,
      while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK
      20, with the exception of Merkel cell carcinomas, and most colorectal
      adenocarcinomas express CK 20. To the best of the authors' knowledge, the present
      case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine
      carcinoma to be described, suggesting a link between colorectal neuroendocrine
      carcinoma and conventional adenocarcinoma.

PMID- 15998385
TI  - Emerging topics in stable isotope ecology: are there isotope effects in plant
      respiration?

PMID- 15998386
TI  - Ectomycorrhizas and mast fruiting in trees: linked by climate-driven tree
      resources?

PMID- 15998387
TI  - West African legumes: the role of nodulation and nitrogen fixation.

PMID- 15998388
TI  - The evolution of mycorrhiza-like associations in liverworts: an update.

PMID- 15998389
TI  - The evolutionary ecology of myco-heterotrophy.
AB  - Nonphotosynthetic mycorrhizal plants have long attracted the curiosity of
      botanists and mycologists, and they have been a target for unabated controversy
      and speculation. In fact, these puzzling plants dominated the very beginnings of
      the field of mycorrhizal biology. However, only recently has the mycorrhizal
      biology of this diverse group of plants begun to be systematically unravelled,
      largely following a landmark Tansley review a decade ago and crucial developments
      in the field of molecular ecology. Here I explore our knowledge of these
      evolutionarily and ecologically diverse plant-fungal symbioses, highlighting
      areas where there has been significant progress. The focus is on what is arguably
      the best understood example, the monotropoid mycorrhizal symbiosis, and the
      overarching goal is to lay out the questions that remain to be answered about the
      biology of myco-heterotrophy and epiparasitism.

PMID- 15998390
TI  - Anatomical and chemical defenses of conifer bark against bark beetles and other
      pests.
AB  - Conifers are long-lived organisms, and part of their success is due to their
      potent defense mechanisms. This review focuses on bark defenses, a front line
      against organisms trying to reach the nutrient-rich phloem. A major breach of the
      bark can lead to tree death, as evidenced by the millions of trees killed every
      year by specialized bark-invading insects. Different defense strategies have
      arisen in conifer lineages, but the general strategy is one of overlapping
      constitutive mechanical and chemical defenses overlaid with the capacity to up
      regulate additional defenses. The defense strategy incorporates a graded response
      from 'repel', through 'defend' and 'kill', to 'compartmentalize', depending upon
      the advance of the invading organism. Using a combination of toxic and polymer
      chemistry, anatomical structures and their placement, and inducible defenses,
      conifers have evolved bark defense mechanisms that work against a variety of
      pests. However, these can be overcome by strategies including aggregation
      pheromones of bark beetles and introduction of virulent phytopathogens. The
      defense structures and chemicals in conifer bark are reviewed and questions about
      their coevolution with bark beetles are discussed.

PMID- 15998391
TI  - Large daily variation in 13C-enrichment of leaf-respired CO2 in two Quercus
      forest canopies.
AB  - The use of the 13C : 12C isotopic ratio (delta13C) of leaf-respired CO2 to trace
      carbon fluxes in plants and ecosystems is limited by little information on
      temporal variations in delta13C of leaf dark-respired CO2 (delta13Cr) under field
      conditions. Here, we explored variability in delta13Cr and its relationship to
      key respiratory substrates from collections of leaf dark-respired CO2,
      carbohydrate extractions and gas exchange measurements over 24-h periods in two
      Quercus canopies. Throughout both canopies, delta13Cr became progressively 13C
      enriched during the photoperiod, by up to 7%, then 13C-depleted at night relative
      to the photoperiod. This cycle could not be reconciled with delta13C of soluble
      sugars (delta13Css), starch (delta13Cst), lipids (delta13Cl), cellulose
      (delta13Cc) or with calculated photosynthetic discrimination (Delta). However,
      photoperiod progressive enrichment in delta13Cr was correlated with cumulative
      carbon assimilation (r2 = 0.91). We concluded that there is considerable short
      term variation in delta13Cr in forest canopies, that it is consistent with
      current hypotheses for 13C fractionation during leaf respiration, that leaf
      carbohydrates cannot be used as surrogates for delta13Cr, and that diel changes
      in leaf carbohydrate status could be used to predict changes in delta13Cr
      empirically.

PMID- 15998392
TI  - Leaf damage induces twining in a climbing plant.
AB  - Successful climbing by vines not only prevents shading by neighbouring
      vegetation, but also may place the vines beyond ground herbivores. Here we tested
      the hypothesis that herbivory might enhance climbing in a vine species, and that
      such induced climbing should be greater in the shade. We assessed field herbivory
      in climbing and prostrate ramets of the twining vine Convolvulus arvensis. We
      evaluated plant climbing after mechanical damage in a glasshouse under both sun
      and shade conditions, and determined whether control and damaged plants differed
      in growth rate or photosynthetic capacity. Plants experienced greater herbivory
      when growing prostrate than when climbing onto companion plants, in both an open
      habitat and a shaded understorey. Experimental plants increased their twining
      rate on a stake after suffering leaf damage, in both high- and low-light
      conditions, and this induced climbing was not coupled to an increase in growth
      rate. Increased photosynthesis was associated with enhanced twining rate only in
      the shade. Herbivory may be an ecological factor promoting the evolution of a
      climbing habit in plants.

PMID- 15998393
TI  - Zinc effects on cadmium accumulation and partitioning in near-isogenic lines of
      durum wheat that differ in grain cadmium concentration.
AB  - Here, we examined the effectiveness of two approaches for reducing cadmium (Cd)
      accumulation in durum wheat (Triticum turgidum L. var durum) grain: the
      application of supplemental zinc (Zn), and the use of cultivars exhibiting
      reduced grain Cd concentrations. Two durum wheat near-isogenic lines (NIL) that
      differ in grain Cd accumulation were grown to maturity in solution culture
      containing a chelating agent to buffer the free activities of Zn and Cd at levels
      approximating those of field conditions. The low Cd accumulating (L-Cd) isoline
      had Cd concentrations, in grains and shoot parts, which were 60-70% lower than
      those of the high Cd accumulating (H-Cd) isoline. Increasing the Zn activities in
      the nutrient solution from deficient to sufficient levels reduced the
      concentration of Cd in grains and vegetative shoot parts of both isolines. The
      results suggest that supplemental Zn reduces Cd tissue concentrations by
      inhibiting Cd uptake into roots. Cd partitioning patterns between roots and
      shoots and between spike components suggest that the physiological basis for the
      low Cd trait is related to the compartmentation or symplasmic translocation of
      Cd.

PMID- 15998394
TI  - Leaf hydraulic architecture correlates with regeneration irradiance in tropical
      rainforest trees.
AB  - The leaf hydraulic conductance (K(leaf)) is a major determinant of plant water
      transport capacity. Here, we measured K(leaf), and its basis in the resistances
      of leaf components, for fully illuminated leaves of five tree species that
      regenerate in deep shade, and five that regenerate in gaps or clearings, in
      Panamanian lowland tropical rainforest. We also determined coordination with
      stomatal characters and leaf mass per area. K(leaf) varied 10-fold across
      species, and was 3-fold higher in sun- than in shade-establishing species. On
      average, 12% of leaf hydraulic resistance (= 1/K(leaf)) was located in the
      petiole, 25% in the major veins, 25% in the minor veins, and 39% outside the
      xylem. Sun-establishing species had a higher proportion of leaf resistance in the
      xylem. Across species, component resistances correlated linearly with total leaf
      resistance. K(leaf) correlated tightly with indices of stomatal pore area,
      indicating a coordination of liquid- and vapor-phase conductances shifted
      relative to that of temperate woody species. Leaf hydraulic properties are
      integrally linked in the complex of traits that define differences in water use
      and carbon economy across habitats and vegetation zones.

PMID- 15998395
TI  - Wound-induced vascular occlusions in tissues of the reed Phragmites australis:
      their development and chemical nature.
AB  - This work focuses on the development of vascular occlusions, which are gels
      resealing the wounded vascular systems of injured organs, in the common reed
      Phragmites australis. Their formation seems to be crucial in keeping the internal
      environment of the plant stable. Histochemical tests, combined with an extraction
      series, were used to follow changes in the chemical nature of gels during their
      development. It was found that the first gel material was secreted by living
      cells in the vicinity of the incision within 1 or 2 d after wounding. Early gels
      were colourless and mainly composed of acidic polysaccharides interlinked by Ca2+
      bridges. The properties of the gel material gradually changed during maturation.
      The matrix of polysaccharides in the early gels was later modified and
      interlinked by other components, resulting in a highly resistant material.
      Structural proteins were identified as the principal interlocking components of
      the material, and were responsible for its high resistance.

PMID- 15998396
TI  - High-resolution time series of vessel density in Kenyan mangrove trees reveal a
      link with climate.
AB  - Tropical trees are often excluded from dendrochronological investigations because
      of a lack of distinct growth ring boundaries, causing a gap in paleoclimate
      reconstructions from tropical regions. The potential use of time series of vessel
      features (density, diameter, surface area and hydraulic conductivity) combined
      with spectral analysis as a proxy for environmental conditions in the mangrove
      Rhizophora mucronata was investigated. Intra-annual differences in the vessel
      features revealed a trade-off between hydraulic efficiency (large vessels) during
      the rainy season and hydraulic safety (small, more numerous vessels) during the
      dry season. In addition to the earlywood-latewood variations, a semiannual signal
      was discovered in the vessel density and diameters after Fourier transformation.
      The similarity in the Fourier spectra of the vessel features and the climate
      data, in particular mean relative humidity and precipitation, provides strong
      evidence for a climatic driving force for the intra-annual variability of the
      vessel features. The high-resolution approach used in this study, in combination
      with spectral analysis, may have great potential for the study of climate
      variability in tropical regions.

PMID- 15998397
TI  - Respiratory carbon losses and the carbon-use efficiency of a northern hardwood
      forest, 1999-2003.
AB  - Quantitative assessment of carbon (C) storage by forests requires an
      understanding of climatic controls over respiratory C loss. Ecosystem respiration
      can be estimated biometrically as the sum (R Sigma) of soil (Rs), leaf (Rl) and
      wood (Rw) respiration, and meteorologically by measuring above-canopy nocturnal
      CO2 fluxes (Fcn). Here we estimated R Sigma over 5 yr in a forest in Michigan,
      USA, and compared R Sigma and Fcn on turbulent nights. We also evaluated forest
      carbon-use efficiency (Ec = P(NP)/P(GP)) using biometric estimates of net primary
      production (P(NP)) and R Sigma and Fcn-derived estimates of gross primary
      production (P(GP)). Interannual variation in R Sigma was modest (142 g C m(-2)
      yr(-1)). Mean annual R Sigma was 1425 g C m(-2) yr(-1); 71% from Rs, 18% from Rl,
      and 11% from Rw. Hourly R Sigma was well correlated with Fcn, but 11 to 58%
      greater depending on the time of year. Greater R Sigma compared with Fcn resulted
      in higher estimated annual P(GP) and lower annual Ec (0.42 vs 0.54) using
      biometric and meteorological data, respectively. Our results provide one of the
      first multiyear estimates of R Sigma in a forested ecosystem, and document the
      responses of component respiratory C losses to major climatic drivers. They also
      provide the first assessment of Ec in a deciduous forest using independent
      estimates of P(GP).

PMID- 15998398
TI  - On the role of flavonoids in the integrated mechanisms of response of Ligustrum
      vulgare and Phillyrea latifolia to high solar radiation.
AB  - The role of flavonoids in mechanisms of acclimation to high solar radiation was
      analysed in Ligustrum vulgare and Phillyrea latifolia, two Mediterranean shrubs
      that have the same flavonoid composition but differ strikingly in their leaf
      morpho-anatomical traits. In plants exposed to 12 or 100% solar radiation,
      measurements were made for surface morphology and leaf anatomy; optical
      properties, photosynthetic pigments, and photosystem II efficiency; antioxidant
      enzymes, lipid peroxidation and phenylalanine ammonia lyase; synthesis of
      hydroxycinnamates and flavonoids; and the tissue-specific distribution of
      flavonoid aglycones and ortho-dihydroxylated B-ring flavonoid glycosides. A
      denser indumentum of glandular trichomes, coupled with both a thicker cuticle and
      a larger amount of cuticular flavonoids, allowed P. latifolia to prevent highly
      damaging solar wavelengths from reaching sensitive targets to a greater degree
      than L. vulgare. Antioxidant enzymes in P. latifolia were also more effective in
      countering light-induced oxidative load than those in L. vulgare. Consistently,
      light-induced accumulation of flavonoids in L. vulgare, particularly ortho
      dihydroxylated flavonoids in the leaf mesophyll, greatly exceeded that in P.
      latifolia. We conclude that the accumulation of flavonoid glycosides associated
      with high solar radiation-induced oxidative stress and, hence, biosynthesis of
      flavonoids appear to be unrelated to 'tolerance' to high solar radiation in the
      species examined.

PMID- 15998399
TI  - Nutrient resorption in wetland macrophytes: comparison across several regions of
      different nutrient status.
AB  - This study explored patterns of nutrient resorption in wetland macrophytes to
      test the prediction that plants from regions with a strong nutrient limitation
      will show higher resorption of the limiting nutrient. Nitrogen and phosphorus
      resorption was assessed in macrophytes from marshes of different nutrient status
      in tropical and temperate regions, and expressed as resorption efficiency (NRE,
      PRE) and proficiency (NRP, PRP). Macrophytes were grouped into three categories:
      Typha, graminoids and broadleaved plants. Nitrogen was less limiting than P,
      consequently N availability varied less than P availability, NRP and NRE were
      lower, and N resorption was mostly incomplete. NRP was determined more by growth
      form than by local conditions. The large range of soil P concentrations allowed
      an exploration of relationships between P availability and resorption along a
      wide gradient. P-limited macrophytes (N : P > 16) had significantly higher PRP
      and PRE. Resorption proficiency was found to be a more sensitive indicator of
      changes in nutrient availability than resorption efficiency. The results
      confirmed that resorption in wetland macrophytes depends on nutrient
      availability, and is higher at nutrient-limited sites. A particularly strong
      relationship was found between resorption indicators and P limitation expressed
      either as live tissue N : P or soil P.

PMID- 15998400
TI  - Nitrogen management and senescence in two maize hybrids differing in the
      persistence of leaf greenness: agronomic, physiological and molecular aspects.
AB  - Here, nitrogen management within the plant was compared in an early-senescing
      maize hybrid and in a late-senescing maize hybrid, both grown under field
      conditions with a high fertilisation input involving large quantities of
      fertiliser. We monitored, in representative leaf stages, the changes in
      metabolite content, enzyme activities and steady-state levels of transcripts for
      marker genes of N primary assimilation, N recycling and leaf senescence. The
      hybrids differed in terms of persistence of leaf greenness, the expression of
      marker genes and the concentration of enzymes used to describe the transition
      from N assimilation to N recycling. The transcription of leaf-senescence marker
      genes did not differ. Agronomic studies confirmed the ability of the late
      senescing hybrid to absorb and store more N in shoots. Despite the differences in
      the mode of N management adopted by the two hybrids, we conclude that leaf
      senescence occurs independently of the source-to-sink transition at the high
      level of fertilisation used involving large quantities of fertiliser. The
      possibility of improving N metabolic efficiency in the latest maize hybrids is
      discussed.

PMID- 15998401
TI  - Linking leaf and root trait syndromes among 39 grassland and savannah species.
AB  - Here, we tested hypothesized relationships among leaf and fine root traits of
      grass, forb, legume, and woody plant species of a savannah community. CO2
      exchange rates, structural traits, chemistry, and longevity were measured in
      tissues of 39 species grown in long-term monocultures. Across species,
      respiration rates of leaves and fine roots exhibited a common regression
      relationship with tissue nitrogen (N) concentration, although legumes had lower
      rates at comparable N concentrations. Respiration rates and N concentration
      declined with increasing longevity of leaves and roots. Species rankings of leaf
      and fine-root N and longevity were correlated, but not specific leaf area and
      specific root length. The C3 and C4 grasses had lower N concentrations than forbs
      and legumes, but higher photosynthesis rates across a similar range of leaf N.
      Despite contrasting photosynthetic pathways and N2-fixing ability among these
      species, concordance in above- and below-ground traits was evident in comparable
      rankings in leaf and root longevity, N and respiration rates, which is evidence
      of a common leaf and root trait syndrome linking traits to effects on plant and
      ecosystem processes.

PMID- 15998402
TI  - Dynamics of heterorhizic root systems: protoxylem groups within the fine-root
      system of Chamaecyparis obtusa.
AB  - To understand the physiology of fine-root functions in relation to soil organic
      sources, the heterogeneity of individual root functions within a fine-root system
      requires investigation. Here the heterogeneous dynamics within fine-root systems
      are reported. The fine roots of Chamaecyparis obtusa were sampled using a
      sequential ingrowth core method over 2 yr. After color categorization, roots were
      classified into protoxylem groups from anatomical observations. The root lengths
      with diarch and triarch groups fluctuated seasonally, whereas the tetrarch root
      length increased. The percentage of secondary root mortality to total mortality
      increased with increasing amounts of protoxylem. The carbon : nitrogen ratio
      indicated that the decomposability of primary roots might be greater than that of
      secondary roots. The position of diarch roots was mostly apical, whereas tetrarch
      roots tended to be distributed in basal positions within the root architecture.
      We demonstrate the heterogeneous dynamics within a fine-root system of C. obtusa.
      Fine-root heterogeneity should affect soil C dynamics. This heterogeneity is
      determined by the branching position within the root architecture.

PMID- 15998403
TI  - Legume species identity and soil nitrogen supply determine symbiotic nitrogen
      fixation responses to elevated atmospheric [CO2].
AB  - In nitrogen (N)-limited systems, the response of symbiotic N fixation to elevated
      atmospheric [CO2] may be an important determinant of ecosystem responses to this
      global change. Experimental tests of the effects of elevated [CO2] have not been
      consistent. Although rarely tested, differences among legume species and N supply
      may be important. In a field free-air CO2 enrichment (FACE) experiment, we
      determined, for four legume species, whether the effects of elevated atmospheric
      [CO2] on symbiotic N fixation depended on soil N availability or species
      identity. Natural abundance and pool-dilution 15N methods were used to estimate N
      fixation. Although N addition did, in general, decrease N fixation, contrary to
      theoretical predictions, elevated [CO2] did not universally increase N fixation.
      Rather, the effect of elevated [CO2] on N fixation was positive, neutral or
      negative, depending on the species and N addition. Our results suggest that
      legume species identity and N supply are critical factors in determining
      symbiotic N-fixation responses to increased atmospheric [CO2].

PMID- 15998404
TI  - Mycorrhizas improve nitrogen nutrition of Trifolium repens after 8 yr of
      selection under elevated atmospheric CO2 partial pressure.
AB  - Altered environmental conditions may change populations of arbuscular mycorrhizal
      fungi and thereby affect mycorrhizal functioning. We investigated whether 8 yr of
      free-air CO2 enrichment has selected fungi that differently influence the
      nutrition and growth of host plants. In a controlled pot experiment, two sets of
      seven randomly picked single spore isolates, originating from field plots of
      elevated (60 Pa) or ambient CO2 partial pressure (pCO2), were inoculated on
      nodulated Trifolium repens (white clover) plants. Fungal isolates belonged to the
      Glomus claroideum or Glomus intraradices species complex, and host plants were
      clonal micropropagates derived from nine genets. Total nitrogen (N) concentration
      was increased in leaves of plants inoculated with fungal isolates from elevated
      pCO2 plots. These isolates took up nearly twice as much N from the soil as
      isolates from ambient-pCO2 plots and showed much greater stimulation of
      biological N2 fixation. The morpho-species identity of isolates had a more
      pronounced effect on N2 fixation and on root length colonized than isolate
      identity. We conclude that rising atmospheric pCO2 may select for fungal strains
      that will help their host plants to meet increased N demands.

PMID- 15998405
TI  - Mast fruiting and seedling survival of the ectomycorrhizal, monodominant Dicymbe
      corymbosa (Caesalpiniaceae) in Guyana.
AB  - In Guyana, we investigated seed output, and resulting seedling establishment and
      survival, during a 'mast' year, by the ectomycorrhizal, monodominant rainforest
      canopy tree Dicymbe corymbosa (Caesalpiniaceae), a species with high, synchronous
      seed production at intermittent years. By utilizing seed traps, the mast seed
      output, predation, carbon and mineral investment, and masting synchrony were
      quantified in 2003 in primary D. corymbosa forests. Establishment of seedling
      cohorts was monitored, and climatic conditions associated with masting were
      assessed. During 2003, D. corymbosa in the Pakaraima Mountains exhibited high,
      synchronous seed production with low dispersal and predation. Investment in
      reproductive biomass was large relative to that in other tropical forests. Recent
      D. corymbosa reproductive events followed El Nino-induced droughts, with little
      intervening seed production. Over 12 months, 40% of the 2003 seedling cohort
      survived. Our results suggest that D. corymbosa has a strongly bimodal fruiting
      pattern that allows the establishment of a large seedling bank, facilitating
      persistent monodominance. Resource investment in large seed crops may depend on
      mineral recycling via ectomycorrhizas, coupled with the reallocation of carbon
      from vegetative maintenance.

PMID- 15998406
TI  - Ectopic expression of the mycorrhiza-specific chitinase gene Mtchit 3-3 in
      Medicago truncatula root-organ cultures stimulates spore germination of glomalean
      fungi.
AB  - Expression of Mtchit 3-3, a class III chitinase gene, is specifically induced by
      arbuscular mycorrhizal (AM) fungi in roots of the model legume Medicago
      truncatula and its transcripts accumulate in cells containing arbuscules.
      Agrobacterium rhizogenes-transformed roots and root-organ cultures of M.
      truncatula were used to study effects of Mtchit 3-3 on AM fungi. * This work
      provides evidence for enzymatic activity of the Mtchit 3-3 gene product and shows
      with promoter:gus fusions that a 2 kb fragment located 5' upstream from the
      translational start codon of Mtchit 3-3 is sufficient to confer arbuscule
      dependent gene expression. By fusing the Mtchit 3-3 coding region to the CaMV 35S
      promoter the expression pattern was disrupted. Surprisingly, disruption
      stimulated spore germination of Glomus intraradices and Glomus constrictum, and
      in the case of G. intraradices resulted in a higher probability of root
      colonization and spore formation. However, no effect on the abundance of
      arbuscules within colonized roots became apparent. These observations demonstrate
      that disruption of the tight arbuscule-dependent expression pattern of Mtchit 3-3
      has effects on the early interaction between roots and AM fungi.

PMID- 15998407
TI  - Polyphosphate dynamics in mycorrhizal roots during colonization of an arbuscular
      mycorrhizal fungus.
AB  - Inorganic polyphosphate (poly P) has been considered to be a translocatable form
      of phosphate (Pi) in arbuscular mycorrhizal fungi (AMF). Here we examined time
      course changes in poly P content during the AMF colonization process. Onion
      (Allium cepa) plants were cultured with or without inoculation with Gigaspora
      margarita for 2-8 wk with periodic sampling. Poly P in the extracts, purified
      through gel filtration, was quantified by the reverse reaction of polyphosphate
      kinase. The length of poly P in mycorrhizal roots appeared to be shorter than in
      extraradical hyphae or in spores of the AMF, indicating that AMF depolymerize
      poly P before providing Pi to the host. The poly P content increased as
      colonization proceeded, and was highly correlated with the weight of the
      colonized roots. These results support the model that AMF supply Pi to the host
      through the poly P pool, and that the poly P content of a mycorrhizal root can be
      a good indicator of the Pi-supplying activity of AMF.

PMID- 15998408
TI  - Spatial patterns of gene expression in the extramatrical mycelium and mycorrhizal
      root tips formed by the ectomycorrhizal fungus Paxillus involutus in association
      with birch (Betula pendula) seedlings in soil microcosms.
AB  - Functional compartmentation of the extramatrical mycelium of ectomycorrhizal
      (ECM) fungi is considered important for the operation of ECM associations,
      although the molecular basis is poorly characterized. Global gene expression
      profiles of mycelium colonizing an ammonium sulphate ((NH4)2SO4) nutrient patch,
      rhizomorphs and ECM root tips of the Betula pendula-Paxillus involutus
      association were compared by cDNA microarray analysis. The expression profiles of
      rhizomorphs and nutrient patch mycelium were similar to each other but distinctly
      different from that of mycorrhizal tips. Statistical analyses revealed 337 of
      1075 fungal genes differentially regulated among these three tissues. Clusters of
      genes exhibiting distinct expression patterns within specific tissues were
      identified. Genes implicated in the glutamine synthetase/glutamate synthase
      (GS/GOGAT) and urea cycles, and the provision of carbon skeletons for ammonium
      assimilation via beta-oxidation and the glyoxylate cycle, were highly expressed
      in rhizomorph and nutrient patch mycelium. Genes implicated in vesicular
      transport, cytoskeleton organization and morphogenesis and protein degradation
      were also differentially expressed. Differential expression of genes among the
      extramatrical mycelium and mycorrhizal tips indicates functional specialization
      of tissues forming ECM associations.

PMID- 15998409
TI  - Direct and indirect defences induced by piercing-sucking and chewing herbivores
      in Medicago truncatula.
AB  - Direct and indirect defences against feeding induced by chewing (Spodoptera
      littoralis) and piercing-sucking (Tetranychus urticae) herbivores, as well as
      components of signal transduction, were investigated in the model legume Medicago
      truncatula. Emitted volatiles, representing a mechanism of indirect defence, were
      measured and identified by gas chromatography/mass spectrometry (GC-MS). As
      elements of direct defence, the accumulation of phenolic compounds and of
      reactive oxygen species (ROS) was assessed using microscopic techniques. Jasmonic
      acid (JA) and salicylic acid (SA) concentrations were assessed as putative
      components of signal transduction. Volatile profiles revealed a sizeable number
      of different substances emitted, particularly sesquiterpenoids. The qualitative
      composition clearly differed depending on the type of herbivory. The same held
      true for JA and SA concentrations. Also, deposition of phenolic compounds and the
      production of ROS around the wounding sites could be detected. Conspicuous
      differences were found in indirect defence and signalling for different types of
      herbivory. In contrast, no divergence in direct defences was observed;
      furthermore, the traits investigated exhibited striking similarities to reactions
      known to occur upon pathogen attack.

PMID- 15998410
TI  - Induction of systemic protection against rust infection in broad bean by
      saccharin: effects on plant growth and development.
AB  - Here, we examine the effect of saccharin on the induction of systemic resistance
      in broad bean (Vicia faba) to the rust fungus Uromyces viciae-fabae. Saccharin
      was applied to beans at the three-leaf stage, either as a soil drench or by
      painting the solution on to first leaves. Plants were then challenge inoculated
      with the rust 1, 6, 10 and 14 d following saccharin treatment, after which they
      were harvested, assessed for the intensity of rust infection and plant growth
      measurements conducted. Foliar application of saccharin did not induce systemic
      protection to rust infection until 14 d after application and was less effective
      than saccharin applied as a soil drench. When saccharin was applied as a drench,
      systemic protection was not observed until 6 d after application, but was still
      apparent in plants 14 d after application of the drench. Irrespective of the
      method of application, saccharin had no significant effect on fresh and dry
      weights or leaf area of the plants. Saccharin applied as a drench did, however,
      reduce the number of leaflets produced.

PMID- 15998411
TI  - Comparing metabolomes: the chemical consequences of hybridization in plants.
AB  - Hybridization may lead to unique phytochemical expression in plant individuals.
      Hybrids may express novel combinations or extreme concentrations of secondary
      metabolites or, in some cases, produce metabolites novel to both parental
      species. Here we test whether there is evidence for extreme metabolite expression
      or novelty in F1 hybrids between Senecio aquaticus and Senecio jacobaea.
      Hybridization is thought to occur frequently within Senecio, and hybridization
      might facilitate secondary metabolite diversification within this genus. Parental
      species express different quantities of several classes of compounds known to be
      involved in antiherbivore defence, including pyrrolizidine alkaloids, chlorogenic
      acid, flavonoids and benzoquinoids. Hybrids demonstrate differential expression
      of some metabolites, producing lower concentrations of amino acids, and perhaps
      flavonoids, than either parental species. Despite evidence for quantitative
      hybrid novelty in this system, NMR profiling did not detect any novel compounds
      among the plant groups studied. Metabolomic profiling is a useful technique for
      identifying qualitative changes in major metabolites according to plant species
      and/or genotype, but is less useful for identifying small differences between
      plant groups, or differences in compounds expressed in low concentrations.

PMID- 15998416
TI  - Use of mycophenolate in the treatment of autoimmune hepatitis.

PMID- 15998412
TI  - Hybridization and genome size evolution: timing and magnitude of nuclear DNA
      content increases in Helianthus homoploid hybrid species.
AB  - Hybridization and polyploidy can induce rapid genomic changes, including the gain
      or loss of DNA, but the magnitude and timing of such changes are not well
      understood. The homoploid hybrid system in Helianthus (three hybrid-derived
      species and their two parents) provides an opportunity to examine the link
      between hybridization and genome size changes in a replicated fashion. Flow
      cytometry was used to estimate the nuclear DNA content in multiple populations of
      three homoploid hybrid Helianthus species (Helianthus anomalus, Helianthus
      deserticola, and Helianthus paradoxus), the parental species (Helianthus annuus
      and Helianthus petiolaris), synthetic hybrids, and natural hybrid-zone
      populations. Results confirm that hybrid-derived species have 50% more nuclear
      DNA than the parental species. Despite multiple origins, hybrid species were
      largely consistent in their DNA content across populations, although H.
      deserticola showed significant interpopulation differences. First- and sixth
      generation synthetic hybrids and hybrid-zone plants did not show an increase from
      parental DNA content. First-generation hybrids differed in DNA content according
      to the maternal parent. In summary, hybridization by itself does not lead to
      increased nuclear DNA content in Helianthus, and the evolutionary forces
      responsible for the repeated increases in DNA content seen in the hybrid-derived
      species remain mysterious.

PMID- 15998417
TI  - MARS preconditioning for living donor liver transplantation: panacea or placebo?

PMID- 15998418
TI  - Changing disease burden of hepatocellular carcinoma in the Far East and Southeast
      Asia.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and
      has a marked difference in geographic distribution. More than 80% of HCC cases
      occur in developing countries, especially the Far East and Southeast Asia.
      Although immunization has been successful against hepatitis B virus (HBV), a
      changing disease burden of HCC has been observed in many parts of the world
      because of the increasing prevalence and duration of hepatitis C virus (HCV)
      infection in these countries. In addition, the age-specific incidence of HCC has
      progressively shifted toward younger people. Hepatitis B genotypes B and C are
      prevalent in the Far East and Southeast Asia, and the clinical relevance of HBV
      genotypes has become increasingly recognized. Compared with genotype C, genotype
      B is associated with earlier hepatitis B e antigen seroconversion, slower
      progression to cirrhosis and less frequent development of HCC. By using periodic
      examinations of serum alfa-fetoprotein levels and abdominal ultrasonography,
      small HCC can be detected and treated earlier. However, prevention of HBV and HCV
      infections as well as effective treatment of the chronic viral infections with
      timely interventions are still needed for the global control of HCC, particularly
      in the Far East and Southeast Asia.

PMID- 15998419
TI  - p53 Mutations in human cholangiocarcinoma: a review.
AB  - The reported mortality from intrahepatic bile duct tumours is increasing markedly
      in industrialised countries, for reasons that remain unknown. Inactivation of the
      tumour suppressor gene p53, is the commonest genetic abnormality in human cancer
      and has been implicated in the genesis of cholangiocarcinoma in various
      immunohistochemical and molecular epidemiological investigations, including gene
      sequencing studies. The structure and function of p53 and its role in linking
      cancer to specific carcinogens by way of mutational signatures is reviewed. The
      findings of previous p53 studies and their relevance in human cholangiocarcinoma
      are summarised.

PMID- 15998420
TI  - Successful treatment of hepatitis C reinfection with interferon-alpha2b and
      ribavirin after liver transplantation.
AB  - INTRODUCTION: Recurrence of hepatitis C virus (HCV) infection after orthotopic
      liver transplantation (OLT) is a virtually universal occurrence, and a
      significant proportion of patients develop chronic hepatitis and cirrhosis. The
      aim of this study was to evaluate the safety and efficacy of interferon (IFN)
      alpha2b plus ribavirin (RIBA) in the treatment of recurrent HCV after OLT over
      the long term. MATERIAL AND METHODS: Fifteen patients with recurrent HCV
      infection (positive serum HCV RNA, elevated serum aminotransferases, histological
      activity) were started on IFN-alpha2b (3-6 million units administered
      subcutaneously three times a week) plus RIBA (800-1200 mg/day) 18+/-5 months
      after OLT. HCV RNA was determined 1, 3, 6, 9, 12 and 18 months after initiation
      of treatment. Liver biopsy was performed before and after therapy. The patients
      were followed up for a mean of 33+/-5 months. RESULTS: Thirteen patients (87%)
      were treated for at least 6 months and nine patients (60%) for 12 months. After 3
      months, 11 patients (73%) were free from HCV RNA (<50 copies/ml); the virological
      end-of-treatment response was 67%. Five patients (33%) remained HCV RNA-negative
      6 months posttreatment (sustained response (SR)). During the follow-up period,
      four patients (27%) died of liver failure, recurrent HCV after virological
      response, or HCC. The histological activity index improved significantly for both
      inflammatory activity and fibrosis, from 8.8 to 4.7 and from 7.3 to 4.8,
      respectively. In none of the patients were signs of rejection observed.
      CONCLUSION: Combination therapy with IFN and RIBA in transplanted patients with
      chronic hepatitis C is an effective treatment that results in a high virological
      SR rate. It is well tolerated and leads to an improvement in histological
      outcome.

PMID- 15998421
TI  - Transplant immunosuppressive agents in non-transplant chronic autoimmune
      hepatitis: the Canadian association for the study of liver (CASL) experience with
      mycophenolate mofetil and tacrolimus.
AB  - BACKGROUND: Conventional treatment of autoimmune hepatitis consists of either
      prednisone alone or in combination with azathioprine. Ten to 20% of patients do
      not respond to or are intolerant of this treatment. Novel drug treatments include
      immunosuppressive drugs such as tacrolimus (TAC), mycophenolate mofetil (MMF),
      methotrexate and cyclosporine. We describe a multi-centre Canadian experience
      with MMF and TAC. OBJECTIVE: To study a multi-centre patient population who had
      failed conventional therapy and were treated with non-conventional medical
      therapy for autoimmune hepatitis and document response. METHODS: Members of the
      Canadian Association for the Study of Liver (CASL) obtained MMF from Hoffmann-La
      Roche Ltd, as part of a compassionate release program, were contacted for
      standardized data on patients with AIH who received MMF or TAC. Response
      definitions based on aminotransferase changes were: Complete response (CR)
      sustained normalization, partial response (PR)-improvement by greater than 50%,
      non-response (NR)-less than 50% improvement and relapse (RP)-initial CR or PR
      followed by an increase in aminotransferases. RESULTS: A total of 16 patients
      were identified: six in Ontario, one in Quebec, five in Alberta and four in
      British Columbia. Three were treated with TAC, eleven with MMF and two with
      combination MMF and TAC. CR was observed in 50%, PR in 12.5%, RP in 25% and NR
      occurred in 12.5%. The CR for MMF without TAC was approximately 64%. CONCLUSIONS:
      MMF is effective and well tolerated by patients with autoimmune hepatitis who do
      not respond to, or are intolerant of, conventional immunosuppressive agents.

PMID- 15998422
TI  - Early treatment response predicts the need for liver transplantation in
      autoimmune hepatitis.
AB  - BACKGROUND: The need for immunosuppression in autoimmune hepatitis is
      established. Previous studies have investigated short-term outcomes in patients
      who respond to treatment. This study assesses long-term prognosis of patients who
      fail to respond to standard immunosuppression. METHODS: 163 charts were reviewed,
      composed of 108 non-transplant patients and 55 patients who required liver
      transplantation (LT). Clinical endpoints were based on aminotransaminases: early
      treatment response (ER) was a 50% improvement at 6 months of therapy, Complete
      remission (CR) was an improvement to <2X normal, Relapse was worsening to >3X
      normal, Incomplete response (IR) was some response but no CR in 3 years, and No
      response (NR) was no improvement after 3 years. RESULTS: 85% of non-LT and 25% of
      LT patients achieved ER, 91% of non-LT and 26% of LT patients achieved CR. 41% of
      non-LT patients relapsed on maintenance treatment, and 41% of non-LT patients
      relapsed when withdrawn from treatment. 9% of non-LT and 58% of LT patients had
      IR. 16% in LT group showed NR, while all non-LT patients showed some response.
      All paired comparisons were statistically different (P<0.05). Multiple regression
      analysis revealed that lack of ER predicts need for LT (P=0.0005). 87% of
      patients who achieved ER did not require LT, whereas 16% of patients who failed
      ER showed NR and all required LT. Odds ratio of a patient who failed ER
      proceeding to LT, compared to a patient who achieved ER, was 16.8 (7.5 to 37.7,
      95% CI). CONCLUSION: Patients who fail to show a 50% improvement in transaminases
      at 6 months of standard immunosuppression should be considered for alternate
      treatment modalities or be referred earlier for LT.

PMID- 15998423
TI  - Autoimmune hepatitis type 1: safety and efficacy of prolonged medical therapy.
AB  - AIM: To assess the efficacy and safety of prolonged medical therapy for up to
      four decades in a cohort of patients with AIH. METHODS: Forty-two patients were
      followed long term in the Yale Liver Clinics who met the criteria of 'definite
      autoimmune hepatitis' as defined by the International Autoimmune Hepatitis Group.
      Records were reviewed for the dosage of immunosuppression, rate of relapse,
      steroid side effects, current status of liver function tests and evidence for
      cirrhosis and its complications. RESULTS: Mean follow-up was 16 years and ranged
      from 7 to 43 years. The median follow-up was 13.5 years. Steroid withdrawal
      resulted in a mean of 1.78 relapses/patient (range, 0-8). All but six patients
      responded well to prednisone and azathioprine and alanine aminotransferases were
      completely normal in 29 (81%) at last exam. Five patients have discontinued
      medication. Steroid side effects have been minimal (weight gain in eight,
      osteoporosis in three) except for one patient who recovered successfully from
      cryptococcal meningitis and another with aseptic necrosis of the hip. Progression
      to cirrhosis occurred in 54% with evidence of esophageal varices in 37% but none
      developed hepatocellular carcinoma. Only one patient has received a liver
      transplant, while five others are currently listed because of symptoms of
      ascites, encephalopathy or bleeding from esophageal varices. CONCLUSIONS: AIH can
      be managed effectively over three to four decades with low-dose immunosuppression
      resulting in essentially normal lifestyles and minimal side effects. Liver
      transplantation with an increased risk of rejection and graft failure in this
      group can be avoided for long periods in most of these patients.

PMID- 15998424
TI  - Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis
      and severe liver failure evaluated for living donor liver transplantation -- a
      pilot study.
AB  - PURPOSE: The aim of this prospective study was to evaluate the effectiveness of
      preconditioning molecular adsorbent recirculating system (MARS) treatment on
      patients with acute-on-chronic liver failure (AoCLF), who were awaiting living
      donor liver transplantation (LDLT). PATIENTS AND METHODS: Between January and
      December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia
      (>20 mg/dl) and hepatic encephalopathy grade > or =2) were studied. MARS was used
      in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF
      patients who received LDLT before clinical use of MARS were used as historical
      controls. RESULTS: Because of a shortage of donors, only five out of 10 patients
      considered for LDLT could receive transplants. Three patients were treated with
      MARS for 8 h the day before receiving LDLT, and all three survived. The remaining
      two patients who received transplants, and who were not pretreated with MARS,
      died from sepsis and multi-organ failure within 2 weeks. Four of the patients who
      did not receive transplants because of donor shortage died despite 1 or 3 MARS
      treatments, however bilirubin levels and grade of encephalopathy were
      significantly reduced in these patients. CONCLUSIONS: Results of this small pilot
      study suggest that MARS, by reducing the severity of jaundice and encephalopathy,
      might be effective as a bridging option in AoCLF patients awaiting LDLT.

PMID- 15998425
TI  - Non-interferon-based therapy: an option for amelioration of necro-inflammation in
      hepatitis C patients who cannot afford interferon therapy.
AB  - OBJECTIVES: Interferon (IFN) therapy is not affordable by the majority of
      Egyptian patients. Our aim was to tailor an effective and inexpensive regimen
      that ameliorates hepatic necro-inflammatory activity among chronic hepatitis C
      (CHC) patients. METHODS: One hundred and seventy naive CHC patients with elevated
      alanine aminotransferase (ALT) (>1.5-fold) and detectable hepatitis C virus (HCV)
      RNA by polymerase chain reaction, who cannot afford IFN-based therapy were
      randomly allocated either to non-interferon-based therapy (N-IFN-BT) (group I) or
      silymarin therapy (group II). Group I comprised 87 patients (biopsy proved
      chronic hepatitis in 62 patients) who were administered a daily combination of
      ribavirin (600-800 mg) plus amantadine (200 mg) and ursodeoxycholic acid (UDCA)
      (500 mg) for 24 weeks. Group II comprised 83 patients who were administered
      Silymarin 450 mg/day for 24 weeks. RESULTS: Statistical evaluation was conducted
      on 82 patients from group I and 72 from group II because of the withdrawal of
      five and 11 patients from Groups I and II, respectively. Age, sex, social status
      and biochemical parameters were comparable in both groups. Normalization of ALT
      at the end of treatment was achieved in 58.5% and 15.3% (P<0.001), whereas end of
      treatment virologic response (ETVR) was achieved in 2.4% and 0% of Groups I and
      II, respectively. Twenty-four weeks after cessation of therapy, sustained
      biochemical response (SBR) was achieved in 28% and 2.8% (P<0.001), while
      sustained virologic response (SVR) was maintained in 2.4% and 0% of the patients
      in Groups I and II, respectively. In Group I, histopathological examination
      revealed a decreased activity index by an average score of 1.5 points among 38/62
      of the rebiopsied patients. CONCLUSION: Twenty-four weeks N-IFN-BT achieved a
      fourfold-higher ETBR and a tenfold-higher SBR compared with silymarin therapy,
      which reflects an improvement of necroinflammatory activity as proven by repeat
      histopathology.

PMID- 15998426
TI  - Adiponectin levels among patients with chronic hepatitis B and C infections and
      in response to IFN-alpha therapy.
AB  - AIMS: The study was designed to survey the change of adiponectin levels before
      and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis
      B and C infections. METHODS: Twenty-one biopsy-proved patients with chronic
      hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a
      total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were
      obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin
      suppression test was conducted before and within 1 week after IFN-alpha therapy.
      RESULTS: The change of adiponectin levels differed significantly between
      responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (
      4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and
      change in body mass index, the study found the change of adiponectin levels still
      significantly related to the response to IFN-alpha (P=0.04). When hepatitis B
      virus (HBV) and hepatitis C virus (HCV)-infected patients were separately
      analyzed, the adiponectin levels reported a trend to decrease in HCV responders
      (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1
      vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of
      steady-state plasma glucose in insulin suppression test was noted in responders
      (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1
      11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. CONCLUSIONS: IFN-alpha
      resulted in a decrease of serum adiponectin levels but an improvement of insulin
      resistance in responders to the treatment. The result contradicts previous
      concept of the relationship between insulin resistance and adiponectin levels.
      Whether and how the augmented immune response, which was supposed to result from
      the disappearance or the profound down-regulation of the virus or viral antigens
      in responders to IFN-alpha treatment, contributes to the lowering of adiponectin
      levels needs to be further investigated.

PMID- 15998427
TI  - Hepatic gene expression in patients with obesity-related non-alcoholic
      steatohepatitis.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is among the most common
      causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic
      syndromes that includes non-alcoholic steatohepatitis (NASH) that has potential
      for progression. The pathogenesis of NASH is poorly characterized. AIM: This
      study was designed to identify differences in hepatic gene expression in patients
      with NASH and to relate such differences to their clinical characteristics.
      DESIGN: Consecutive patients undergoing bariatric surgery were prospectively
      recruited. Extensive clinical data and two liver biopsy specimens were obtained
      at the time of enrollment. A single hepatopathologist reviewed and classified the
      liver biopsies. Patients with excessive alcohol use and other causes of liver
      disease were excluded. A group of 29 NASH patients, 12 with steatosis alone,
      seven obese controls and six non-obese controls were selected for further
      investigation. Customized cDNA microarrays containing 5220 relevant genes were
      designed specifically for this study. Microarray experiments were run in
      triplicate for each sample and a selected group of genes were confirmed using
      real-time PCR. OUTCOME MEASURE: Differential hepatic gene expressions in patients
      with NASH as compared with controls. RESULTS: Thirty-four genes with significant
      differential expression were identified in patients with NASH when compared with
      non-obese controls. Moreover, 19 of these genes showed no significant expression
      differences in obese vs. non-obese controls, suggesting a stronger association of
      these genes to NASH. CONCLUSIONS: Several differentially expressed genes in
      patients with NASH are related to lipid metabolism and extracellular matrix
      remodeling. Additionally, genes related to liver regeneration, apoptosis, and the
      detoxification process were differentially expressed. These findings may help
      clarify the molecular pathogenesis of NASH and identify potential targets for
      therapeutic intervention.

PMID- 15998428
TI  - Lower incidence of hepatic failure than hepatocellular carcinoma in Japanese
      patients with chronic hepatitis C.
AB  - BACKGROUND: Previous studies have shown that the development of hepatic failure
      was found more frequently than that of hepatocellular carcinoma (HCC) in patients
      with chronic hepatitis C in the United States and European countries. We
      investigated the status in Japan in a retrospective cohort study. METHODS: The
      incidences of HCC and hepatic failure were accessed in 459 patients with biopsy
      proven C-viral chronic liver disease with a mean follow-up period of 8.9+/-3.2
      years and the cause of death was also analyzed in the cohort. RESULTS: HCC
      developed in 63 patients, 46 of 355 interferon (IFN)-treated and 17 of 104
      untreated patients. In contrast, the development of hepatic failure was found in
      18 patients, 12 of 355 IFN-treated and six of 104 untreated patients. HCC
      developed in four of 116 with sustained virological response (SVR), and hepatic
      failure developed in one of them. Thirty-two of 63 patients developing HCC and
      eight of 18 patients developing hepatic failure died. CONCLUSIONS: Development of
      hepatic failure was less frequent than that of HCC in Japan. It is important for
      a favorable prognosis of patients with C viral chronic liver disease to achieve a
      higher SVR and thus inhibit the development of HCC in Japan.

PMID- 15998429
TI  - Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients
      with non-alcoholic fatty liver disease.
AB  - AIM: To determine whether serum hyaluronic acid reliably predicts the severity of
      hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).
      METHODS: We studied 79 patients with histologically confirmed NAFLD. Hyaluronic
      acid was measured in serum obtained at the time of liver biopsy. Severity of
      fibrosis was staged based on Brunt's classification. The prediction levels for
      fibrosis were determined by area under the receiver operating characteristic
      curve (AUC). RESULTS: The logarithm of serum hyaluronic acid was significantly
      different among the stages of fibrosis (P<0.0001, analysis of variance) and had a
      significant positive correlation with the degrees of fibrosis after adjusting for
      age and serum albumin (partial r=0.44, P<0.0001). AUCs were 0.67, 0.87, 0.89, and
      0.92 for any levels of fibrosis, > or =moderate fibrosis, > or =severe fibrosis,
      and cirrhosis, all of which were significantly higher than 0.5 (P<0.05). The cut
      off value of serum hyaluronic acid of 46.1 mug/l was associated with the highest
      AUC for severe fibrosis, yielding a sensitivity of 85% and a specificity of 80%.
      The corresponding positive and negative predictive values were 51% and 96%, when
      assuming prevalence of severe fibrosis in NAFLD patients of 20% at referral
      centers. CONCLUSIONS: Measurement of serum hyaluronic acid is useful to identify
      NAFLD patients with severe fibrosis.

PMID- 15998430
TI  - Correlation of nitric oxide and atrial natriuretic peptide changes with altered
      cGMP homeostasis in liver cirrhosis.
AB  - BACKGROUND: Cyclic GMP (cGMP) concentration is increased in plasma of patients
      with liver cirrhosis. Three possible mechanisms may contribute: increased cGMP
      synthesis by soluble (activated by nitric oxide), or particulate (activated by
      atrial natriuretic peptide (ANP)) guanylate cyclase or increased release from
      cells. AIM: The aim of this work was to analyze the possible contributors to
      increased plasma cGMP and to assess whether changes in the parameters of the
      system vary with the degree of liver disease (Child Pugh score) or by the
      presence of ascites. METHODS: We measured cGMP in plasma and lymphocytes, soluble
      guanylate cyclase activation by nitric oxide in lymphocytes, nitrates and
      nitrites and ANPs (activator of particulate guanylate cyclase) in plasma. We
      analyzed the correlation between changes in different parameters to discern which
      parameters contribute to increased plasma cGMP. RESULTS: The plasma content of
      nitrates+nitrites, ANP and cGMP are increased. Activation of soluble guanylate
      cyclase by nitric oxide is increased in patients while basal cGMP in lymphocytes
      is decreased. CONCLUSIONS: Both increased ANP and increased activation of soluble
      guanylate cyclase by nitric oxide contribute to increased plasma cGMP in
      patients. The concentrations of ANP and cGMP in plasma increase with the degree
      of disease and are higher in patients with ascites.

PMID- 15998431
TI  - Treatment of experimental hepatic fibrosis by combinational delivery of urokinase
      type plasminogen activator and hepatocyte growth factor genes.
AB  - PURPOSE: To investigate the effect of combinational delivery of urokinase-type
      plasminogen activator (uPA) and hepatocyte growth factor (HGF) genes on hepatic
      fibrosis. METHODS: Replication-deficient adenoviral vectors expressing either
      human HGF (AdHGF) or uPA (AduPA) were generated. HGF gene was transferred into
      primary cultured hepatocytes and uPA gene to hepatic stellate cell (HSC) to
      investigate the effect on the biological character of cells. Combinational
      adenoviruses were infused into hepatic fibrosis rats. Serum markers as well as
      histological and immunohistochemical examination were carried out to test the
      reversal of hepatic fibrosis. RESULTS: Transfection of exogenous HGF gene induced
      expression of c-met/HGF receptor and stimulated hepatocyte proliferation. uPA
      gene delivered into HSC decreased the amount of collagen types I and III
      accompanied with the increased expression of matrix metalloproteinase-2. In vivo,
      the area of extracellular matrix in the fibrotic liver decreased to 72% in AdHGF
      treated rats (P<0.01), 64% in the AduPA-treated group (P<0.01), and 51% in bi
      genes transfection (P<0.01), compared with that of the controls. Moreover,
      immunohistochemical staining of collagen types I and III revealed that
      combinational genes delivery exerted more effect on reversal of hepatic fibrosis
      than mono-gene transfection. CONCLUSIONS: Our study indicated that simultaneous
      delivery of two antifibrotic genes could confer synergistic effect on hepatic
      fibrosis.

PMID- 15998432
TI  - Somatostatin inhibits pro-inflammatory cytokine secretion from rat hepatic
      stellate cells.
AB  - BACKGROUND/AIMS: Activated hepatic stellate cells (HSCs) have been implicated in
      hepatic fibrosis. Somatostatin (SOM) has an immunomodulatory role. The aim of
      this study was to assess the secretion of pro-inflammatory cytokines by HSCs and
      to determine the effect of SOM on the secretion of these mediators. METHODS:
      Activated rat HSCs were evaluated for their secretion of IL-1beta, IL-8, and TNF
      alpha using ELISA. RNA protection assay was used to determine cytokine mRNA
      levels. The expression of chemokine and cytokine mRNA and the secretion of these
      mediators were assessed following incubation with SOM or octreotide. RESULTS:
      HSCs spontaneously secreted IL-1beta, IL-8, and TNF-alpha. This secretion was
      augmented following stimulation by IL-1beta and TNF-alpha. SOM inhibited the
      spontaneous and TNF-alpha-induced secretion of IL-1beta, IL-8, and TNF-alpha and
      suppressed the expression of IL-1beta and TNF-alpha mRNA. Octreotide suppressed
      the secretion of IL-1beta and IL-8. CONCLUSIONS: These observations indicate that
      SOM exerts an inhibitory immunomodulatory effect on HSCs.

PMID- 15998433
TI  - Diffuse expression of heparan sulfate proteoglycan and connective tissue growth
      factor in fibrous septa with many mast cells relate to unresolving hepatic
      fibrosis of congenital hepatic fibrosis.
AB  - BACKGROUND AND AIMS: Congenital hepatic fibrosis (CHF) is characterized by dense
      portal/septal fibrosis and bile duct proliferation and tortuosity. In this study,
      the roles and significance of fibrosis-related cells and molecules in the process
      of progressive and unresolving fibrosis of CHF were examined in comparison with
      other fibrotic liver diseases. METHODS: Seven CHF livers were examined, and a
      total of 74 control livers (chronic viral hepatitis (CVH), alcoholic
      fibrosis/cirrhosis (F/C), extrahepatic biliary obstruction and livers showing non
      specific reactive changes) were used as controls. All of these livers were wedge
      biopsied or surgically resected ones, and were formalin fixed and paraffin
      embedded. In addition to histologic observations, expression of heparan sulfate
      proteoglycan (HSPG), connective tissue growth factor (CTGF), mast cell-specific
      tryptase, alpha-smooth muscle actin for activated hepatic stellate cells (HSC) or
      myofibroblasts (MF) were immunohistochemically surveyed. HSPG and CTGF at mRNA
      were also examined by in situ hybridization. RESULTS: Portal/septal fibrosis of
      CHF were mature collagenous and elastic fiber poor, when compared with controls.
      HSPG and CTGF were diffusely abundant in fibrous portal tracts/septa in CHF,
      while they were more or less accentuated at periportal areas in alcoholic F/C and
      CVH. In CHF, the number of interface and portal/septal MF was increased from mild
      to-moderate degree, while their increase was moderate to marked in alcoholic F/C
      and CVH, particularly F3/F4. While activated HSC were frequent in alcoholic F/C
      and CVH and they were continuous with interface MF, activated HSC in CHF were
      scanty. Instead, mast cells were increased in portal/septal fibrosis of CHF.
      Portal mononuclear cells and endothelial cells were positive for HSPG mRNA, and
      mononuclear cells for CTGF mRNA, and such cells were accentuated around
      proliferated bile ducts and ductules in CHF. CONCLUSIONS: Abundant CTGF retained
      diffusely in HSPG in the fibrous portal tracts/septa may be responsible for non
      resolving hepatic fibrosis in CHF, and many mast cells and portal MF not related
      to HSC may causally relate to such characteristic finding in CHF.

PMID- 15998434
TI  - Fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, suppresses collagen
      production and enhances collagenase activity in hepatic stellate cells.
AB  - BACKGROUND/AIMS: The Rho-ROCK signaling pathways play an important role in the
      activation of hepatic stellate cells (HSCs). We investigated the effects of
      fasudil hydrochloride hydrate (fasudil), a Rho-kinase (ROCK) inhibitor, on cell
      growth, collagen production, and collagenase activity in HSCs. METHODS: Rat HSCs
      and human HSC-derived TWNT-4 cells were cultured for studies on stress fiber
      formation and alpha-smooth muscle actin (alpha-SMA) expression. Proliferation was
      measured by BrdU incorporation, and apoptosis by TUNEL assay. The phosphorylation
      states of the MAP kinases (MAPKs), extra cellular signal -regulated kinase 1/2
      (ERK1/2), c-jun kinase (JNK), and p38 were evaluated by western blot analysis.
      Type I collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1) production and gene expression were evaluated
      by ELISA and real-time PCR, respectively. Collagenase activity (active MMP-1) was
      also evaluated. RESULTS: Fasudil (100 microM) inhibited cell spreading, the
      formation of stress fibers, and expression of alpha-SMA with concomitant
      suppression of cell growth, although it did not induce apoptosis. Fasudil
      inhibited phosphorylation of ERK1/2, JNK, and p38. Treatment with fasudil
      suppressed the production and transcription of collagen and TIMP, stimulated the
      production and transcription of MMP-1, and enhanced collagenase activity.
      CONCLUSION: These findings demonstrated that fasudil not only suppresses
      proliferation and collagen production but also increases collagenase activity.

PMID- 15998435
TI  - Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is
      restricted to a subset of hepatocellular carcinoma.
AB  - BACKGROUND: While the Wnt pathway has been widely implicated in
      hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of
      beta-catenin-lymphoid enhancer factor-1 (LEF-1)/T-cell factor (TCF) signaling is
      controversely discussed. METHODS: By immunohistochemical analyses we studied the
      subcellular localization of LEF-1/TCF and cyclin D1 in 162 hepatocellular
      carcinoma (HCC). Single- and double-label imaging by brightfield and confocal
      laser scanning microscopy was quantitated and correlated with beta-catenin, the
      Ki67(+) proliferation fraction (PF), tumor size, grade, the Okuda stage and
      patient survival. RESULTS: The frequency of nuclear cyclin D1 expression was 28%
      and closely correlated with LEF-1/TCF (P<0.0001) and the Ki67(+) PF (P=0.03).
      Nuclear LEF-1/TCF expression was observed in 52% of all cases, but was also
      present in 42% of cyclin D1(-) cases. Nuclear beta-catenin was identified in 37%
      of all HCCs and correlated with LEF-1/TCF (P=0.04). The expression of cyclin D1,
      LEF-1/TCF or beta-catenin did not correlate with other clinico-pathological data.
      CONCLUSIONS: A large proportion of HCCs does not appear to be linked to a
      deregulation of cyclin D1. However, the coordinated expression of cyclin D1 and
      LEF-1/TCF in some cases suggests the role of cyclin D1 as a Wnt target gene in a
      subset of HCCs.

PMID- 15998436
TI  - Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and
      pathologic features of hepatocellular carcinoma.
AB  - AIM: We investigated pathological features of Lens culinaris agglutinin-reactive
      alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to
      seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3.
      METHODS: A total of 111 patients with HCC < or =5 cm in diameter who underwent
      hepatic resection were studied. Serum AFP-L3 concentration was measured within a
      month prior to surgery by lectin-affinity electrophoresis coupled with antibody
      affinity blotting, and expressed as AFP-L3 percentage of total AFP. AFP-L3 of 10%
      or higher was judged to be positive. Pathologic features of resected HCC
      specimens were evaluated and classified concerning growth pattern (expansive or
      infiltrative growth), capsule formation, capsule infiltration, septal formation,
      portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic
      metastasis. These macroscopic and microscopic findings were compared between AFP
      L3-positive and negative HCC specimens. RESULTS: Thirty-three (29.7%) were
      positive for AFP-L3. The prevalence of HCC with infiltrative growth, with capsule
      infiltration, with septum formation, with portal vein invasion, and with hepatic
      vein invasion was significantly higher in AFP-L3-positive group (P=0.0121,
      0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features
      reportedly indicate the progression of the tumor. CONCLUSIONS: AFP-L3-positive
      HCC had several pathologic features of progressed state of HCC, which accounted
      for the AFP-L3 as an indicator of poor prognosis of HCC.

PMID- 15998437
TI  - Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas:
      implications for an improved chemotherapy of primary liver tumors.
AB  - BACKGROUND/AIMS: The hepatocyte receptor for asialoglycoproteins (ASGP-R)
      internalizes macromolecules exposing galactosyl residues (MEGRs) which can be
      used as liver-addressed drug carriers. This receptor was also found on the cells
      of the large majority of well differentiated hepatocarcinomas (HCCs). The aim of
      the present experiments was to ascertain whether ASGP-R of HCCs is functionally
      active and these tumors can internalize higher quantities of MEGRs than extra
      hepatic tissues. METHODS: We injected radioactive lactosaminated human albumin (L
      HSA) in rats with HCCs produced by nitroso-diethylamine and measured the
      radioactivity of tumors, surrounding liver, heart, intestine and kidney. L-HSA is
      a MEGR successfully used in humans as a hepatotropic drug carrier. RESULTS: The
      levels of radioactivity of HCCs were two to three times lower than those of
      surrounding liver, but several times higher than those of extra-hepatic tissues.
      L-HSA accumulation in the tumors mainly occurred via the ASGP-R, as indicated by
      the 20 times lower penetration of non-lactosaminated HSA. L-HSA uptake by the
      well-differentiated tumors were four times higher compared with that by the
      poorly differentiated forms. CONCLUSIONS: The present results suggest that in the
      chemotherapy of HCCs expressing the ASGP-R the extra-hepatic toxicity of
      anticancer agents can be reduced by conjugation to L-HSA.

PMID- 15998438
TI  - Zonation of alanine metabolism in the bivascularly perfused rat liver.
AB  - AIMS/BACKGROUND: Zonation of alanine metabolism was investigated in the
      bivascularly perfused rat liver, a technique in which a selective area of the
      periportal region can be reached via the hepatic artery. METHODS: Bivascular
      liver perfusion was done in both the antegrade and retrograde modes. Predominance
      of a given metabolic parameter in the periportal or perivenous area was deduced
      from comparisons of the changes caused by alanine infusion into the hepatic
      artery in antegrade and retrograde perfusion. RESULTS: Confirming previous
      notions, glutamine synthesis predominated in the perivenous area, however, the
      contribution of the periportal area was significant. Gluconeogenesis and the
      associated extra oxygen consumption were more pronounced in the periportal
      region. The capacity of urea synthesis in the periportal region was relatively
      small as indicated by the ratios of urea to glucose production, which were lower
      in this region. Ammonia in the periportal region was considerably above the mean
      ammonia production of whole the liver parenchyma. The overflows of pyruvate and
      lactate were considerably smaller in the periportal region. CONCLUSION: The
      distribution of alanine metabolism seems to reflect mainly zonation of the fates
      of the carbon skeleton (mainly gluconeogenesis). The production of glutamine in
      the periportal area is in agreement with recent reports about the presence of
      glutamine synthetase in Kupffer and endothelial cells.

PMID- 15998439
TI  - Mechanism of protective action of bicyclol against CCl-induced liver injury in
      mice.
AB  - Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis
      in China. This paper reports the protective action of bicyclol against
      experimental liver injury in mice and its mechanism of action. Oral
      administration of bicyclol markedly reduced the elevated serum transaminases
      (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the
      hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies
      demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid
      peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal
      lipids and proteins in vitro, and decreased the level of the trichloromethyl free
      radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver
      microsomes. On the other hand, bicyclol neither directly inhibited the activity
      of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These
      results suggest that bicyclol has remarkable hepatoprotective effects and its
      mechanism of action may be related to a decrease in free radical-induced damage
      to hepatocytes.

PMID- 15998440
TI  - Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative
      damage and apoptosis.
AB  - INTRODUCTION: Oxidative damage plays a major part in the pathogenesis of liver
      disease. Uncoupling proteins (UCPs) may be able to limit the generation of
      reactive oxygen species (ROS) and be cytoprotective. METHODS: We investigated the
      effect of up-regulation of UCP2 in a hepatoblastoma cell line exposed to
      menadione or hypoxia/re-oxygenation. RESULTS: Lipid and protein oxidation was
      increased in HepG2 cells exposed to ROS but this increase was significantly lower
      in cells over-expressing UCP2 under identical conditions. LDH release increased
      2.5-fold in response to hypoxia/re-oxygenation in control HepG2 cells with no
      significant increase in UCP2 transfected cells. Hypoxia/re-oxygenation resulted
      in a reduction in liver-specific protein secretion that was attenuated in
      transfected cells and UCP2 over-expression also resulted in a 66% reduction in
      apoptosis compared with non-transfected controls. CONCLUSIONS: These data suggest
      that UCP2 can limit oxidative damage in HepG2 cells in response to oxidative
      stress resulting in improved cell function and resistance to apoptosis.

PMID- 15998441
TI  - Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans
      Cinnamon rats.
AB  - OBJECTIVES: Long-Evans Cinnamon (LEC) rats are characterized by an abnormal
      hepatic deposition of copper (Cu) due to a lack of the Cu-transporter P-type
      adenosine triphosphatase: accordingly, the strain is a good animal model of
      Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the
      development of acute hepatitis and the biochemical parameters of Cu-induced liver
      damage was studied in 5-week-old LEC rats (n=52). METHODS: Rats receiving 50 or
      80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of
      glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks
      after the start of treatment. RESULTS: Treatment with Zn acetate resulted in the
      prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and
      symptoms compatible with acute hepatitis between the 6th and 7th week of
      treatment. Tissue metallothionein (MT) significantly increased in the treated
      rats and positively correlated with Zn concentrations within the liver. Control
      rats had a significantly higher iron concentration in the liver and kidneys
      compared with supplemented rats, after both short- and long-term experiments. 8
      hydroxy-2'-deoxyguanosine amounts were significantly lower in untreated rats.
      CONCLUSIONS: Zn acetate prevents acute hepatitis, by increasing tissue MT
      concentrations, reducing Cu absorption and interfering with Fe metabolism.

PMID- 15998442
TI  - Intracellular localization of NS3 and C proteins in chronic hepatitis C.
AB  - AIMS AND METHODS: The cellular localization of hepatitis C virus (HCV) proteins
      in chronic hepatitis C remains a debatable issue. Aim of the studies included
      cellular and subcellular localization of two HCV proteins, NS3 and C protein, in
      liver biopsies from 20 children with chronic hepatitis C employing commercially
      available monoclonal antibodies and a semiquantitative technique of the proteins
      expression. In the studies advantage was taken of (Strept)avidin-biotin
      peroxidase complex and ImmunoMax technique. RESULTS: The cytoplasmic localization
      of both proteins dominated over nuclear localization. The total amount of NS3
      protein exceeded that of C protein. At the ultrastructural level, we observed
      both proteins in endoplasmic reticulum membranes and mitochondria, but small
      amount of both proteins was seen also in cell nuclei. The amount of either
      protein did not correlate with liver histology in our patients. No correlation
      could be disclosed between content of both proteins and HCV RNA levels in serum.
      Content of NS3 demonstrated negative correlation with activity of alanine
      transaminase. CONCLUSION: In conclusion, the new aspect in present studies
      involved localization of C and NS3 proteins at the levels of light and electron
      microscopy in children. For the first time also intramitochondrial localization
      of NS3 protein was demonstrated.

PMID- 15998443
TI  - Effect of diphenyl dimethyl bicarboxylate on concanavalin A-induced liver injury
      in mice.
AB  - Diphenyl dimethyl bicarboxylate (DDB) is a hepatoprotectant and used in the
      treatment of chronic viral hepatitis patients in China. The aim of the present
      paper was to investigate the effect of DDB on liver injury mediated by immune
      response in concanavalin A (Con A)-treated mice. A dose of Con A 30 mg/kg was
      injected via the tailvein to induce liver injury in mice. Serum alanine
      transaminase (ALT), aspartate aminotransferase (AST), total bile acid (TBA),
      total bilirubin (TBIL) and tumor necrosis factor alpha (TNF-alpha) level as well
      as liver TNF-alpha mRNA expression were determined. The following results were
      obtained: (1) Prior oral administration of DDB 150 mg/kg markedly reduced the
      elevated serum ALT, TBA and TBIL levels, and the liver lesions in Con A-treated
      mice; (2) DDB significantly inhibited the elevation of serum TNF-alpha and liver
      TNF-alpha mRNA expression 2 h after Con A injection; (3) DDB significantly
      inhibited hepatocyte nuclear DNA fragmentation 12 h after Con A injection; (4)
      DDB dose-dependently prevented the direct DNA damage induced by CuSO(4)-Phen-Vit
      C-H(2)O(2) system in vitro, and the ex vivo experiment also showed that the
      administration of DDB reduced the susceptibility of mouse liver nuclei DNA to
      CuSO(4)-Phen-Vit C-H(2)O(2) system. These results suggest that DDB could directly
      protect hepatocyte DNA from oxidative damage, and inhibit TNF-alpha mRNA
      expression in liver tissue, which resulted in prevention of liver damage induced
      by Con A in mice.

PMID- 15998444
TI  - Effects of sildenafil citrate on hepatic function and regeneration in normal and
      alcohol-fed rats.
AB  - Sildenafil citrate is a potent inhibitor of specific phosphodiesterase-5, which
      mediates metabolism of intracellular second message -- cGMP. Sildenafil citrate
      has been widely used for erectile dysfunction in men. Moreover, it is known that
      men with liver diseases have higher rate of erectile dysfunction. Furthermore, it
      has been demonstrated that nitric oxide plays an important role in liver function
      and regeneration. The present study evaluates effects of sildenafil citrate on
      hepatic function and regeneration in normal and alcohol-fed rats. In normal rats
      sildenafil citrate has a trend to improve hepatic function after partial
      hepatectomy (PHx). Moreover, sildenafil citrate significantly reduces hepatic
      regenerative activity at the concentration of 5 mg/kg body weight. However,
      sildenafil had no effects on hepatic function and regeneration of alcohol-fed
      rats. In general, sildenafil citrate did not induce significant changes in
      hepatic function and regenerative activity after PHx in normal and alcohol-fed
      rats, except at concentration of 5 mg/kg sildenafil citrate significantly inhibit
      hepatic regeneration in normal rats.

PMID- 15998445
TI  - Relationship between the tissue-specificity of mouse gene expression and the
      evolutionary origin and function of the proteins.
AB  - BACKGROUND: The combination of complete genome sequence information with
      expression data enables us to characterize the relationship between a protein's
      evolutionary origin or functional category and its expression pattern. In this
      study, mouse proteins were assigned into functional and phyletic groups and the
      gene expression patterns of the different protein groupings were examined by
      microarray analysis in various mouse tissues. RESULTS: Our results suggest that
      the proteins that are universally distributed in all tissues are predominantly
      enzymes and transporters. In contrast, the tissue-specific set is dominated by
      regulatory proteins (signal transduction and transcription factors). An increased
      tendency to tissue-specificity is observed for metazoan-specific proteins. As the
      composition of the phyletic groups highly correlates with that of the functional
      groups, the data were tested in order to determine which of the two factors --
      function or phyletic age -- is dominant in shaping the expression profile of a
      protein. The observed differences in expression patterns of genes between
      functional groups were found mainly to reflect their different phyletic origin.
      The connection between tissue specificity and phyletic age cannot be explained by
      the recent rate of evolution. Finally, although metazoan-specific proteins tend
      to be tissue-specific compared with phyletically conserved proteins present in
      all domains of life, many such 'universal' proteins are also tissue-specific.
      CONCLUSION: The minimal cellular transcriptome of the metazoan cell differs from
      that of the ancestral unicellular eukaryote: new functions were added (metazoan
      specific proteins), whilst other functions became specialized and no longer took
      place in all cells (tissue-specific pre-metazoan proteins).

PMID- 15998446
TI  - Functional analysis of human and chimpanzee promoters.
AB  - BACKGROUND: It has long been argued that changes in gene expression may provide
      an additional and crucial perspective on the evolutionary differences between
      humans and chimpanzees. To investigate how often expression differences seen in
      tissues are caused by sequence differences in the proximal promoters, we tested
      the expression activity in cultured cells of human and chimpanzee promoters from
      genes that differ in mRNA expression between human and chimpanzee tissues.
      RESULTS: Twelve promoters for which the corresponding gene had been shown to be
      differentially expressed between humans and chimpanzees in liver or brain were
      tested. Seven showed a significant difference in activity between the human
      promoter and the orthologous chimpanzee promoter in at least one of the two cell
      lines used. However, only three of them showed a difference in the same direction
      as in the tissues. CONCLUSION: Differences in proximal promoter activity are
      likely to be common between humans and chimpanzees, but are not linked in a
      simple fashion to gene-expression levels in tissues. This suggests that several
      genetic differences between humans and chimpanzees might be responsible for a
      single expression difference and thus that relevant expression differences
      between humans and chimpanzees will be difficult to predict from cell culture
      experiments or DNA sequences.

PMID- 15998447
TI  - Creation and disruption of protein features by alternative splicing -- a novel
      mechanism to modulate function.
AB  - BACKGROUND: Alternative splicing often occurs in the coding sequence and alters
      protein structure and function. It is mainly carried out in two ways: by skipping
      exons that encode a certain protein feature and by introducing a frameshift that
      changes the downstream protein sequence. These mechanisms are widespread and well
      investigated. RESULTS: Here, we propose an additional mechanism of alternative
      splicing to modulate protein function. This mechanism creates a protein feature
      by putting together two non-consecutive exons or destroys a feature by inserting
      an exon in its body. In contrast to other mechanisms, the individual parts of the
      feature are present in both splice variants but the feature is only functional in
      the splice form where both parts are merged. We provide evidence for this
      mechanism by performing a genome-wide search with four protein features:
      transmembrane helices, phosphorylation and glycosylation sites, and Pfam domains.
      CONCLUSION: We describe a novel type of event that creates or removes a protein
      feature by alternative splicing. Current data suggest that these events are rare.
      Besides the four features investigated here, this mechanism is conceivable for
      many other protein features, especially for small linear protein motifs. It is
      important for the characterization of functional differences of two splice forms
      and should be considered in genome-wide annotation efforts. Furthermore, it
      offers a novel strategy for ab initio prediction of alternative splice events.

PMID- 15998448
TI  - Genomic analysis of metabolic pathway gene expression in mice.
AB  - BACKGROUND: A segregating population of (C57BL/6J x DBA/2J)F2 intercross mice was
      studied for obesity-related traits and for global gene expression in liver.
      Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait
      and all gene-expression data. These data were then used to identify gene sets
      that are differentially perturbed in lean and obese mice. RESULTS: We integrated
      global gene-expression data with phenotypic and genetic segregation analyses to
      evaluate metabolic pathways associated with obesity. Using two approaches we
      identified 13 metabolic pathways whose genes are coordinately regulated in
      association with obesity. Four genomic regions on chromosomes 3, 6, 16, and 19
      were found to control the coordinated expression of these pathways. Using
      criteria that included trait correlation, differential gene expression, and
      linkage to genomic regions, we identified novel genes potentially associated with
      the identified pathways. CONCLUSION: This study demonstrates that genetic and
      gene-expression data can be integrated to identify pathways associated with
      clinical traits and their underlying genetic determinants.

PMID- 15998450
TI  - Transcript copy number estimation using a mouse whole-genome oligonucleotide
      microarray.
AB  - The ability to quantitatively measure the expression of all genes in a given
      tissue or cell with a single assay is an exciting promise of gene-expression
      profiling technology. An in situ-synthesized 60-mer oligonucleotide microarray
      designed to detect transcripts from all mouse genes was validated, as well as a
      set of exogenous RNA controls derived from the yeast genome (made freely
      available without restriction), which allow quantitative estimation of absolute
      endogenous transcript abundance.

PMID- 15998449
TI  - Analysis of the Macaca mulatta transcriptome and the sequence divergence between
      Macaca and human.
AB  - We report the initial sequencing and comparative analysis of the Macaca mulatta
      transcriptome. Cloned sequences from 11 tissues, nine animals, and three species
      (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the
      generation of 48,642 sequence reads. These data represent an initial sampling of
      the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity
      within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina,
      and M. mulatta are also reported.

PMID- 15998451
TI  - Validation and refinement of gene-regulatory pathways on a network of physical
      interactions.
AB  - As genome-scale measurements lead to increasingly complex models of gene
      regulation, systematic approaches are needed to validate and refine these models.
      Towards this goal, we describe an automated procedure for prioritizing genetic
      perturbations in order to discriminate optimally between alternative models of a
      gene-regulatory network. Using this procedure, we evaluate 38 candidate
      regulatory networks in yeast and perform four high-priority gene knockout
      experiments. The refined networks support previously unknown regulatory
      mechanisms downstream of SOK2 and SWI4.

PMID- 15998452
TI  - Genomic analysis of heat-shock factor targets in Drosophila.
AB  - We have used a chromatin immunoprecipitation-microarray (ChIP-array) approach to
      investigate the in vivo targets of heat-shock factor (Hsf) in Drosophila embryos.
      We show that this method identifies Hsf target sites with high fidelity and
      resolution. Using cDNA arrays in a genomic search for Hsf targets, we identified
      141 genes with highly significant ChIP enrichment. This study firmly establishes
      the potential of ChIP-array for whole-genome transcription factor target mapping
      in vivo using intact whole organisms.

PMID- 15998453
TI  - Eighty years ago.

PMID- 15998454
TI  - Conservation anchors in the vertebrate genome.
AB  - Genomic segments that do not code for proteins yet show high conservation among
      vertebrates have recently been identified by various computational methodologies.
      We refer to them as ANCORs (ancestral non-coding conserved regions). The
      frequency of individual ANCORs within the genome, along with their (correlated)
      inter-species identity scores, helps in assessing the probability that they
      function in transcription regulation or RNA coding.

PMID- 15998455
TI  - Text-mining and information-retrieval services for molecular biology.
AB  - Text-mining in molecular biology -- defined as the automatic extraction of
      information about genes, proteins and their functional relationships from text
      documents -- has emerged as a hybrid discipline on the edges of the fields of
      information science, bioinformatics and computational linguistics. A range of
      text-mining applications have been developed recently that will improve access to
      knowledge for biologists and database annotators.

PMID- 15998456
TI  - The genomics of probiotic intestinal microorganisms.
AB  - An intestinal population of beneficial commensal microorganisms helps maintain
      human health, and some of these bacteria have been found to significantly reduce
      the risk of gut-associated disease and to alleviate disease symptoms. The genomic
      characterization of probiotic bacteria and other commensal intestinal bacteria
      that is now under way will help to deepen our understanding of their beneficial
      effects.

PMID- 15998458
TI  - Molecular helminthology in the Rockies. Keystone Symposium on Molecular
      Helminthology, Copper Mountain, Colorado, USA, 9-13 April 2005.

PMID- 15998459
TI  - Meeting the challenges of drug discovery: a multidisciplinary re-evaluation of
      current practices. Keystone Symposium 'Meeting the Challenges of Drug Discovery',
      Vancouver, Canada, 15-19 January 2005.

PMID- 15998460
TI  - Complex cell behaviors in development: recent progress and emerging challenges.
      British Societies for Cell Biology and Developmental Biology Joint Spring
      Meeting, University of Warwick, Coventry, UK, 6-9 April 2005.

PMID- 15998457
TI  - The cyclophilins.
AB  - Cyclophilins (Enzyme Commission (EC) number 5.1.2.8) belong to a group of
      proteins that have peptidyl-prolyl cis-trans isomerase activity; such proteins
      are collectively known as immunophilins and also include the FK-506-binding
      proteins and the parvulins. Cyclophilins are found in all cells of all organisms
      studied, in both prokaryotes and eukaryotes; humans have a total of 16
      cyclophilin proteins, Arabidopsis up to 29 and Saccharomyces 8. The first member
      of the cyclophilins to be identified in mammals, cyclophilin A, is the major
      cellular target for, and thus mediates the actions of, the immunosuppressive drug
      cyclosporin A. Cyclophilin A forms a ternary complex with cyclosporin A and the
      calcium-calmodulin-activated serine/threonine-specific protein phosphatase
      calcineurin; formation of this complex prevents calcineurin from regulating
      cytokine gene transcription. Recent studies have implicated a diverse array of
      additional cellular functions for cyclophilins, including roles as chaperones and
      in cell signaling.

PMID- 15998461
TI  - Transcription regulation: no holy grail, but many treasures. Biochemical Society
      Annual Symposium 'Transcription UK', London, UK, 13-15 April 2005.

PMID- 15998462
TI  - New names for old strains? Wolbachia wSim is actually wRi.

PMID- 15998463
TI  - Correction: Serendipitous discovery of Wolbachia genomes in multiple Drosophila
      species.
AB  - A correction to Serendipitous discovery of Wolbachia genomes in multiple
      Drosophila species by SL Salzberg, JC Dunning Hotopp, AL Delcher, M Pop, DR
      Smith, MB Eisen and WC Nelson. Genome Biology 2005, 6:R23.

PMID- 15998464
TI  - Determinants of response to a parent questionnaire about development and
      behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.
AB  - BACKGROUND: We aimed to determine how response to a parent-completed postal
      questionnaire measuring development, behaviour, impairment, and parental concerns
      and anxiety, varies in different European centres. METHODS: Prospective cohort
      study of 3 year old children, with and without congenital toxoplasmosis, who were
      identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7
      countries. Parents were mailed a questionnaire that comprised all or part of
      existing validated tools. We determined the effect of characteristics of the
      centre and child on response, age at questionnaire completion, and response to
      child drawing tasks. RESULTS: The questionnaire took 21 minutes to complete on
      average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to
      participate. The strongest determinants of response were the score for
      organisational attributes of the study centre (such as direct involvement in
      follow up and access to an address register), and infection with congenital
      toxoplasmosis. Age at completion was associated with study centre, presence of
      neurological abnormalities in early infancy, and duration of prenatal treatment.
      Completion rates for individual questions exceeded 92% except for child completed
      drawings of a man (70%), which were completed more by girls, older children, and
      in certain centres. CONCLUSION: Differences in response across European centres
      were predominantly related to the organisation of follow up and access to correct
      addresses. The questionnaire was acceptable in all six countries and offers a low
      cost tool for assessing development, behaviour, and parental concerns and
      anxiety, in multinational studies.

PMID- 15998465
TI  - Measurement of vaccination coverage at age 24 and 19-35 months: a case study of
      multiple imputation in public health.
AB  - AIM: Childhood immunization coverage in the United States (US) is often measured
      at age 24 months or, in the National Immunization Survey (NIS) at age of
      interview, which is between 19 and 35 months. This paper compares these
      standards. METHODS: Data from the NIS is used to compare immunization coverage at
      time of interview, retrospectively among all children aged 24 or more months at
      time of interview, and obtained via multiple imputation (with 10 imputations) for
      all children, both nationally, by state, and by demographic groups. RESULTS: At
      the national level, the difference between the 19-35 month estimate and the 24
      month complete-case estimate was 1.9 percentage points. For most but not all
      states and subgroups, the 19-35 month estimate was higher than the 24 month
      complete-case estimate. The difference between vaccination coverage measured at
      19-35 months and 24 months ranged from -2.3 to 7.5 percentage points among
      states. For three states, the difference between the 19-35 month and 24 month
      complete-case estimate was more than 6 percentage points, in twelve states there
      was a 4-6 percentage point difference, and in sixteen states a 2-4 percentage
      point difference. Conversely, five states had higher 24 month complete-case
      estimates than 19-35 month estimates. CONCLUSION: We found that the coverages at
      19-35 and 24 months differ such that they would rarely be adequate surrogates for
      one another, particularly at a state level. Multiple imputation, which is easily
      implemented, increases precision of estimates of coverage at age 24 months.

PMID- 15998467
TI  - Efficacy of the epidural blood patch for the treatment of post lumbar puncture
      headache BLOPP: a randomised, observer-blind, controlled clinical trial [ISRCTN
      71598245].
AB  - BACKGROUND: Post dural punction headache (PDPH) occurs in 10% to 40% of the
      patients who had a lumbar puncture. Its symptoms can be severe and
      incapacitating. The epidural blood patch is widely accepted as the treatment of
      choice for postdural puncture headache. Uncontrolled studies report rapid
      recovery after patching in 90% to 100% of treated patients. However, sufficient
      evidence from randomised, controlled clinical trials is lacking. METHODS: BLOPP
      (blood patch for post dural puncture headache) is a randomised, single centre,
      observer-blind clinical trial. Patients with PDPH for at least 24 hours and at
      most 7 days after lumbar puncture will be randomised to treatment with an
      epidural blood patch (EDBP) or to conventional treatment, i.e. 24 hours bed rest
      and ample fluid intake. PDPH 24 hours after treatment, classified on a 4-point
      scale (no, mild, moderate, severe) is the primary outcome. The secondary outcome
      is the presence of PDPH 7 days after treatment. We estimated that a sample size
      of 2 x 20 patients would provide us with a power of 80% to detect a relative
      reduction in number of patients with persisting PDPH after 24 hours of 50% at the
      usual significance level alpha = 5%, taking into account that in approximately
      10% of the patients the PDPH will have resolved spontaneously after one day.
      DISCUSSION: The EDBP is accepted as the treatment of choice for PDPH although
      randomised, controlled data is scarce. Our randomised, observer-blind clinical
      trial enables us to compare the efficacy of two clinically practiced methods of
      PDPH treatment; EDBP versus conventional treatment, as they are applied in
      clinical practise.

PMID- 15998466
TI  - Efficient assembly of de novo human artificial chromosomes from large genomic
      loci.
AB  - BACKGROUND: Human artificial chromosomes (HACs) are potentially useful vectors
      for gene transfer studies and for functional annotation of the genome because of
      their suitability for cloning, manipulating and transferring large segments of
      the genome. However, development of HACs for the transfer of large genomic loci
      into mammalian cells has been limited by difficulties in manipulating high
      molecular weight DNA, as well as by the low overall frequencies of de novo HAC
      formation. Indeed, to date, only a small number of large (>100 kb) genomic loci
      have been reported to be successfully packaged into de novo HACs. RESULTS: We
      have developed novel methodologies to enable efficient assembly of HAC vectors
      containing any genomic locus of interest. We report here the creation of a novel,
      bimolecular system based on bacterial artificial chromosomes (BACs) for the
      construction of HACs incorporating any defined genomic region. We have utilized
      this vector system to rapidly design, construct and validate multiple de novo
      HACs containing large (100-200 kb) genomic loci including therapeutically
      significant genes for human growth hormone (HGH), polycystic kidney disease
      (PKD1) and beta-globin. We report significant differences in the ability of
      different genomic loci to support de novo HAC formation, suggesting possible
      effects of cis-acting genomic elements. Finally, as a proof of principle, we have
      observed sustained beta-globin gene expression from HACs incorporating the entire
      200 kb beta-globin genomic locus for over 90 days in the absence of selection.
      CONCLUSION: Taken together, these results are significant for the development of
      HAC vector technology, as they enable high-throughput assembly and functional
      validation of HACs containing any large genomic locus. We have evaluated the
      impact of different genomic loci on the frequency of HAC formation and identified
      segments of genomic DNA that appear to facilitate de novo HAC formation. These
      genomic loci may be useful for identifying discrete functional elements that may
      be incorporated into future generations of HAC vectors.

PMID- 15998468
TI  - Development of ERK Activity Sensor, an in vitro, FRET-based sensor of
      Extracellular Regulated Kinase activity.
AB  - BACKGROUND: Study of ERK activation has thus far relied on biochemical assays
      that are limited to the use of phospho-specific antibodies and radioactivity in
      vitro, and analysis of whole cell populations in vivo. As with many systems,
      fluorescence resonance energy transfer (FRET) can be utilized to make highly
      sensitive detectors of molecular activity. Here we introduce FRET-based ERK
      Activity Sensors, which utilize variants of Enhanced Green Fluorescent Protein
      fused by an ERK-specific peptide linker to detect ERK2 activity. RESULTS: ERK
      Activity Sensors display varying changes in FRET upon phosphorylation by active
      ERK2 in vitro depending on the composition of ERK-specific peptide linker
      sequences derived from known in vivo ERK targets, Ets1 and Elk1. Analysis of
      point mutations reveals specific residues involved in ERK binding and
      phosphorylation of ERK Activity Sensor 3. ERK2 also shows high in vitro
      specificity for these sensors over two other major MAP Kinases, p38 and
      pSAPK/JNK. CONCLUSION: EAS's are a convenient, non-radioactive alternative to
      study ERK dynamics in vitro. They can be utilized to study ERK activity in real
      time. This new technology can be applied to studying ERK kinetics in vitro,
      analysis of ERK activity in whole cell extracts, and high-throughput screening
      technologies.

PMID- 15998469
TI  - Structural genomics of human proteins--target selection and generation of a
      public catalogue of expression clones.
AB  - BACKGROUND: The availability of suitable recombinant protein is still a major
      bottleneck in protein structure analysis. The Protein Structure Factory, part of
      the international structural genomics initiative, targets human proteins for
      structure determination. It has implemented high throughput procedures for all
      steps from cloning to structure calculation. This article describes the selection
      of human target proteins for structure analysis, our high throughput cloning
      strategy, and the expression of human proteins in Escherichia coli host cells.
      RESULTS AND CONCLUSION: Protein expression and sequence data of 1414 E. coli
      expression clones representing 537 different proteins are presented. 139 human
      proteins (18%) could be expressed and purified in soluble form and with the
      expected size. All E. coli expression clones are publicly available to facilitate
      further functional characterisation of this set of human proteins.

PMID- 15998470
TI  - High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool
      for interpretation of multiple-microarray experiments, with application to
      studies of Common Variable Immune Deficiency (CVID).
AB  - BACKGROUND: We previously developed GoMiner, an application that organizes lists
      of 'interesting' genes (for example, under-and overexpressed genes from a
      microarray experiment) for biological interpretation in the context of the Gene
      Ontology. The original version of GoMiner was oriented toward visualization and
      interpretation of the results from a single microarray (or other high-throughput
      experimental platform), using a graphical user interface. Although that version
      can be used to examine the results from a number of microarrays one at a time,
      that is a rather tedious task, and original GoMiner includes no apparatus for
      obtaining a global picture of results from an experiment that consists of
      multiple microarrays. We wanted to provide a computational resource that
      automates the analysis of multiple microarrays and then integrates the results
      across all of them in useful exportable output files and visualizations. RESULTS:
      We now introduce a new tool, High-Throughput GoMiner, that has those capabilities
      and a number of others: It (i) efficiently performs the computationally-intensive
      task of automated batch processing of an arbitrary number of microarrays, (ii)
      produces a human-or computer-readable report that rank-orders the multiple
      microarray results according to the number of significant GO categories, (iii)
      integrates the multiple microarray results by providing organized, global
      clustered image map visualizations of the relationships of significant GO
      categories, (iv) provides a fast form of 'false discovery rate' multiple
      comparisons calculation, and (v) provides annotations and visualizations for
      relating transcription factor binding sites to genes and GO categories.
      CONCLUSION: High-Throughput GoMiner achieves the desired goal of providing a
      computational resource that automates the analysis of multiple microarrays and
      integrates results across all of the microarrays. For illustration, we show an
      application of this new tool to the interpretation of altered gene expression
      patterns in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner
      will be useful in a wide range of applications, including the study of time
      courses, evaluation of multiple drug treatments, comparison of multiple gene
      knock-outs or knock-downs, and screening of large numbers of chemical derivatives
      generated from a promising lead compound.

PMID- 15998471
TI  - Serum resistin is associated with C-reactive protein & LDL cholesterol in type 2
      diabetes and coronary artery disease in a Saudi population.
AB  - AIMS: Resistin is an adipocyte-derived factor implicated in obesity-associated
      type 2 diabetes (T2DM). This study examines the association between human serum
      resistin, T2DM and coronary heart disease. METHODS: One hundred and fourteen
      Saudi Arabian patients (male: female ratio 46:68; age 51.4 (mean +/- SD)11.7
      years; median and range: 45.59 (11.7) years and BMI: 27.1 (mean +/- SD) 8.1 Kgm2
      median and range: 30.3 (6.3) were studied. Serum resistin and C-reactive protein
      (CRP), a marker of inflammation CRP levels, were measured in all subjects. (35
      patients had type 2 diabetes mellitus (T2DM); 22 patients had coronary heart
      disease (CHD). RESULTS: Serum resistin levels were 1.2-fold higher in type 2
      diabetes and 1.3-fold higher in CHD than in controls (p = 0.01). In addition, CRP
      was significantly increased in both T2DM and CHD patients (p = 0.007 and p =
      0.002 respectively). The use of regression analysis also determined that serum
      resistin correlated with CRP levels (p = 0.04, R2 0.045). CONCLUSION: The
      findings from this study further implicate resistin as a circulating protein
      associated with T2DM and CHD. In addition this study also demonstrates an
      association between resistin and CRP, a marker of inflammation in type 2 diabetic
      patients.

PMID- 15998472
TI  - Rapid and simultaneous detection of human hepatitis B virus and hepatitis C virus
      antibodies based on a protein chip assay using nano-gold immunological
      amplification and silver staining method.
AB  - BACKGROUND: Viral hepatitis due to hepatitis B virus and hepatitis C virus are
      major public health problems all over the world. Traditional detection methods
      including polymerase chain reaction (PCR)-based assays and enzyme-linked
      immunosorbent assays (ELISA) are expensive and time-consuming. In our assay, a
      protein chip assay using Nano-gold Immunological Amplification and Silver
      Staining (NIASS) method was applied to detect HBV and HCV antibodies rapidly and
      simultaneously. METHODS: Chemically modified glass slides were used as solid
      supports (named chip), on which several antigens, including HBsAg, HBeAg, HBcAg
      and HCVAg (a mixture of NS3, NS5 and core antigens) were immobilized
      respectively. Colloidal nano-gold labelled staphylococcal protein A (SPA) was
      used as an indicator and immunogold silver staining enhancement technique was
      applied to amplify the detection signals, producing black image on array spots,
      which were visible with naked eyes. To determine the detection limit of the
      protein chip assay, a set of model arrays in which human IgG was spotted were
      structured and the model arrays were incubated with different concentrations of
      anti-IgG. A total of 305 serum samples previously characterized with commercial
      ELISA were divided into 4 groups and tested in this assay. RESULTS: We prepared
      mono-dispersed, spherical nano-gold particles with an average diameter of 15 +/-
      2 nm. Colloidal nano-gold-SPA particles observed by TEM were well-distributed,
      maintaining uniform and stable. The optimum silver enhancement time ranged from 8
      to 12 minutes. In our assay, the protein chips could detect serum antibodies
      against HBsAg, HBeAg, HBcAg and HCVAg with the absence of the cross reaction. In
      the model arrays, the anti-IgG as low as 3 ng/ml could be detected. The data for
      comparing the protein chip assay with ELISA indicated that no distinct difference
      (P > 0.05) existed between the results determined by our assay and ELISA
      respectively. CONCLUSION: Results showed that our assay can be applied with
      serology for the detection of HBV and HCV antibodies rapidly and simultaneously
      in clinical detection.

PMID- 15998474
TI  - [Ethics and power: training for residents and interns].

PMID- 15998475
TI  - [Factors for expulsion of intrauterine device Tcu380A applied immediately
      postpartum and after a delayed period].
AB  - OBJECTIVE: To determine the frequency of expulsion of the intrauterine device
      TCu380A (IUD) inserted either immediately postpartum or after a delayed period.
      We aimed to identify the factors associated with expulsion. MATERIALS AND
      METHODS: A longitudinal and comparative study was carried out in three Family
      Medicine Units of the Instituto Mexicano del Seguro Social (IMSS) of Leon,
      Guanajuato. One hundred twenty-five women who had a vaginal delivery and who
      elected to have IUD inserted immediately after delivery participated in the study
      along with 125 women who elected to have the IUD inserted after a delayed period
      after delivery. Studied factors were parity, technique, and insertion by the
      doctors assigned to the service and medical personnel in training (pre or
      postdegree). A medical review was performed one month and three months after
      insertion of the IUD. Results were analyzed by chi-square and Student t test.
      RESULTS: The expulsion rates of IUDs during immediate puerperium and also after a
      delayed period were 16 and 2.7%, respectively (p<0.0004). There was no
      statistically significant association between expulsion of the IUD and the
      following factors that were taken into account: age, primipara, personnel who
      inserted the device, and the application technique. In immediate puerperium,
      25.9% of women who had multiple deliveries expelled the IUD, and in those who
      delayed IUD insertion, it was 4% (p=0.03). CONCLUSIONS: There is a greater risk
      of expulsion if the IUD is inserted immediately after delivery and it is
      associated with multiparity. The percentage of expulsion in immediate puerperium
      is similar to that reported in the literature.

PMID- 15998476
TI  - Burnout syndrome among Mexican hospital nursery staff.
AB  - OBJECTIVE: To identify frequency and related factors to burnout syndrome in the
      nursing staff at a specialty hospital in the Mexican state of Guanajuato.
      MATERIALS AND METHODS: A prolective, analytical cross-sectional study was carried
      out. In 236 randomly selected nurses, a 35-item questionnaire proposed by Cyberia
      Shink was applied in a blind survey. Seniority, workplace, shift and kind of
      service, work category, age and marital status were investigated for a link with
      burnout syndrome. RESULTS: Mean age of nursing personnel was 33+/-11.93 years
      with 13+/-7.2 years of seniority; 95 (40%) workers showed emotional exhaustion,
      78 (32%) felt dehumanized, 148 (63%) had lost interest in their work, and 120
      (50%) reported general exhaustion. From the studied nursing personnel, 92 (39%)
      showed burnout syndrome-compatible data. There were statistical differences with
      nurses without burnout syndrome age >33 years (p=0.001), seniority (p=0.05), and
      workplace (p=0.05), but not with kind of medical service (p=0.36), shift
      (p=0.86), and work category (p=0.96). Questionnaire validity in agreement with
      alpha Cronbach test was 0.7496. Relation between professional attrition and work
      environment was r=0.738. CONCLUSIONS: The instrument can be relied upon to
      identify burnout syndrome and is considered as acceptable. Age, seniority, and
      workplace are factors linked to nursing staff with burnout syndrome-compatible
      data. Employers, managers, and supervisors of health care services must promote
      preventive actions for burnout syndrome to synchronize present work conditions in
      nursing staff with their biologic characteristics.

PMID- 15998477
TI  - [Clinical aptitudes of residents in emergency medicine in trauma management].
AB  - OBJECTIVE: To build, validate and apply an instrument to evaluate the clinical
      aptitudes of the emergency medicine residents of different degrees in the
      management of traumatic diseases at six different treatment locations in Mexico
      City. MATERIAL AND METHODS: This was a comparative cross-sectional study that
      evaluates the clinical aptitudes in the management of patients with traumatic
      injuries by residents specializing in emergency medicine at six different
      locations in Mexico City. The instrument was based on four clinical areas being
      validated by a consensus of experts in emergency medicine and educational
      investigation. A consistency of 0.94 within the pilot test was obtained. A non
      parametric statistical analysis was carried out. RESULTS: Included in the study
      were 141 residents from six locations and three with degrees of the specialty. A
      minimum scoring of 3 was obtained and a maximum of 119, with 25 possible answers
      expected by chance. Kruskal-Wallis test did not show significant differences
      among the six locations. To obtain comparison between levels, in only one
      location were significant differences found; 61 % of the residents demonstrated
      low aptitudes, 20.6 % reached intermediate level, 16.3 % showed a very low level,
      and only 0.7 % demonstrated a high level; no resident reached a very high level.
      CONCLUSIONS: The educational process in the analyzed locations appears to not
      promote students generating their own criterion, which negatively affects the
      solution to routine problems.

PMID- 15998478
TI  - [Age of onset of different malignant tumors in childhood].
AB  - OBJECTIVE: To identify the main age of onset of different malignant tumors in
      childhood and to describe the distribution of the different tumors in each
      pediatric age group. MATERIAL AND METHODS: Descriptive survey was used. We
      reviewed the files of six Mexico City hospitals from 1980 to 1992. We included
      4595 cases divided into 13 types of cancer. Peak age was defined when in that
      year we encountered a frequency equal to or below 10 % of the cases. RESULTS:
      Peak ages for hepatic, sympathetic nervous system, germ cell tumors,
      retinoblastoma and rhabdomyosarcoma were between 2 and 3 years of age. Wilms'
      tumor appeared between the first and fourth years; central nervous system tumors
      between 4 and 5 years; acute lymphoblastic leukemia between 2 and 4 years; non
      Hodgkin's lymphomas between 3 and 6 years; Hodgkin's disease between 4 and 8
      years; bone tumors between 10 and 14 years. In acute myeloid leukemia and
      carcinomas no age peak was found. CONCLUSIONS: Lymphomas present an age peak
      different from that reported in developed countries. In neonates and infants, the
      most frequent tumor was retinoblastoma.

PMID- 15998479
TI  - [Origin, functions and expectations of the specialty in nutritional support].
AB  - Considerations are presented on the causes and frequency at the beginning or
      worsening of malnutrition in hospitalized patients. Most of the children had a
      more accelerated metabolism, and we examined how this malnutrition modifies their
      metabolic and functional responses and increases morbidity and mortality. During
      the 20th century the study and treatment with total parenteral nutrition (TPN)
      began. This allows the patient's nourishment to be maintained through the
      administration of nutrients directly into the circulatory system because of the
      inability of the patient to receive food by the digestive route. The benefits, as
      well as the risks and complications of the procedure, have been documented for
      the last 30 years. On the other hand, the technology has allowed the modification
      of the physicochemical characteristics of the nutrients. This is an alternative
      for some of the digestive processes to favor its absorption in the intestine in
      those patients who cannot receive natural nourishment. This procedure is known as
      specialized enteral nutrition (SEN). These two groups of procedures (TPN and SEN)
      are the cornerstones of a new specialty. The meanings of this specialty are
      several, including nutritional support and metabolic support. The adoption of the
      term "endonutrition" is proposed.

PMID- 15998480
TI  - [Pneumobilia. A case report].
AB  - Pneumobilia, gas within the biliary tract, is due to an abnormal connection
      between the gastrointestinal tract and the biliary tract and is considered a
      serious pathology usually requiring surgical intervention. Most cases of
      pneumobilia are related to gallstone disease, and spontaneous biliary-enteric
      fistula is reported to be the most common cause of pneumobilia. Another well
      documented cause of pneumobilia is a surgically created anastomosis between the
      biliary tract and the bowel, the Whipple procedure, and choledocho-jejunostomy,
      endoscopic retrograde cholangiopancreatography with papillosphincterotomy or
      surgical transduodenal sphincteroplasty. Transient incompetence of the sphincter
      of Oddi, gas-forming infections, and trauma have also been reported to cause
      pneumobilia. We present the case of a 74-year-old woman with asymptomatic
      cholelithiasis, pneumobilia and cholecystoduodenal fistula treated with
      cholecystectomy, fistula closure with Graham patch, Stamm-Kader gastrostomy and
      needle catheter jejunostomy. On the first postoperative day she developed a
      biliary duodenal fistula that required nutritional support with parenteral,
      enteral nutrition and octreotide acetate with fistula closure 2 weeks later. We
      review the etiology, surgical treatment and economic burden. Laparoscopic
      cholecysto-fistulectomy by skilled laparoscopic surgeons can be adopted as a
      first-choice treatment for cholecystoduodenal fistula to reduce morbility risks
      and costs.

PMID- 15998481
TI  - [Arsenic intoxication: information and case report].
AB  - Arsine intoxication is a true medical emergency with a high fatality rate,
      characteristic of acute and massive hemolysis. Inhalation of 250 ppm of arsine
      gas is instantly lethal. Exposure to 25 to 50 ppm for 30 minutes is lethal.
      Arsine is a colorless gas with a garlic scent, entering the organism by breathing
      and passing directly into the circulation. Its hemolytic activity is due to its
      ability to cause a fall in erythrocyte-reduced glutathione content.
      Manifestations are suggestive of a general toxic state with alterations of
      consciousness, from confusion until delirium, crash, hematuria, jaundice and
      renal insufficiency. This can generate confusion and difficulty in the diagnosis
      and in the opportune treatment to avoid death or sequelae. This type of
      intoxication must be suspected in electrolysis process workers or those working
      with lead, copper, zinc, iron, gold, silver and tin. In the present case, sources
      for arsenic ingestion in the organism were discarded and the presence of arsine
      in the workplace was confirmed. In spite of the administered treatment, the
      patient experienced renal insufficiency.

PMID- 15998482
TI  - [Clinical guideline for rehabilitation of patients with cervical whiplash at the
      primary care level].
AB  - Whiplash is a sprain of the ligament with strain of the paraspinal muscles due to
      acceleration or back acceleration of energy transmitted to the neck. The symptoms
      are neck pain, neck stiffness, muscular spasm and a multitude of discomforts that
      affect job-related and activities of daily living. In 2000, the Mexican Social
      Security System treated more than 15,000 cases of whiplash due to job-related
      activities. With this information, we organized an expert team in order to
      develop guidelines using methodology of evidence-based medicine and with a focus
      on early treatment prescribed by the general practitioner in order for the
      patient to obtain quick relief and to return the patient to his job and to his
      daily living activities as soon as possible.

PMID- 15998483
TI  - [Cockcroft-Gault formula].

PMID- 15998484
TI  - [Proposal of evaluation instrument].

PMID- 15998485
TI  - [The Mexican Institute of Social Security Institute (IMSS) in Numbers. Functional
      inventory of imaging medical equipment, 2003].
AB  - Medical technology is a fundamental instrument for the provision of health
      services in the Mexican Institute of Social Security (IMSS) and as a support for
      diagnostic and therapeutic interventions. The inventory of relevant medical
      equipment describes the needs for upgrading the technological infrastructure,
      organize its distribution and plan its renovation in order to guarantee the
      quality of health services. In this report we describe the type of equipment used
      in radiology and other imaging services, its geographical distribution, median
      age in operation and its productivity. The inventory reported 2091 pieces of
      equipment, ultrasonography and radiology were the most common types (31%)
      followed by fluoroscopic equipment (20%). Follow-up in the inventory should help
      in planning the acquisition and maintenance of sophisticated technology used for
      medical purposes.

PMID- 15998486
TI  - [Origin of malarial paroxysm].
AB  - This study attempts the reconstruction of the most characteristic clinical
      picture of the acute phase of malaria, the malarial paroxysm, describing the
      elements that participate on the part of the parasite and the host, the way they
      become integrated, and how they function to produce the classical clinical
      manifestations of what we call malaria.

PMID- 15998488
TI  - A stochastic analysis of first-order reaction networks.
AB  - A stochastic model for a general system of first-order reactions in which each
      reaction may be either a conversion reaction or a catalytic reaction is derived.
      The governing master equation is formulated in a manner that explicitly separates
      the effects of network topology from other aspects, and the evolution equations
      for the first two moments are derived. We find the surprising, and apparently
      unknown, result that the time evolution of the second moments can be represented
      explicitly in terms of the eigenvalues and projections of the matrix that governs
      the evolution of the means. The model is used to analyze the effects of network
      topology and the reaction type on the moments of the probability distribution. In
      particular, it is shown that for an open system of first-order conversion
      reactions, the distribution of all the system components is a Poisson
      distribution at steady state. Two different measures of the noise have been used
      previously, and it is shown that different qualitative and quantitative
      conclusions can result, depending on which measure is used. The effect of
      catalytic reactions on the variance of the system components is also analyzed,
      and the master equation for a coupled system of first-order reactions and
      diffusion is derived.

PMID- 15998489
TI  - A note on the asymptotic reduction of the Hodgkin-Huxley equations for nerve
      impulses.
AB  - The (standard) FitzHugh reduction of the Hodgkin-Huxley equations for the
      propagation of nerve impulses ignores the dynamics of the activation gates. This
      assumption is invalid and leads to an over-estimation of the wave speed by a
      factor of 5 and the wrong dependence of wave speed on sodium channel conductance.
      The error occurs because a non-dimensional parameter, which is assumed to be
      small in the FitzHugh reduction, is in fact large (approximately 18). We analyse
      the Hodgkin-Huxley equations for propagating nerve impulses in the limit that
      this non-dimensional parameter is large, and show that the analytical results are
      consistent with numerical simulations of the Hodgkin-Huxley equations.

PMID- 15998490
TI  - Marine reserves with ecological uncertainty.
AB  - To help manage the fluctuations inherent in fish populations scientists have
      argued for both an ecosystem approach to management and the greater use of marine
      reserves. Support for reserves includes empirical evidence that they can raise
      the spawning biomass and mean size of exploited populations, increase the
      abundance of species and, relative to reference sites, raise population density,
      biomass, fish size and diversity. By contrast, fishers often oppose the
      establishment and expansion of marine reserves and claim that reserves provide
      few, if any, economic payoffs. Using a stochastic optimal control model with two
      forms of ecological uncertainty we demonstrate that reserves create a resilience
      effect that allows for the population to recover faster, and can also raise the
      harvest immediately following a negative shock. The tradeoff of a larger reserve
      is a reduced harvest in the absence of a negative shock such that a reserve will
      never encompass the entire population if the goal is to maximize the economic
      returns from harvesting, and fishing is profitable. Under a wide range of
      parameter values with ecological uncertainty, and in the 'worst case' scenario
      for a reserve, we show that a marine reserve can increase the economic payoff to
      fishers even when the harvested population is not initially overexploited,
      harvesting is economically optimal and the population is persistent. Moreover, we
      show that the benefits of a reserve cannot be achieved by existing effort or
      output controls. Our results demonstrate that, in many cases, there is no
      tradeoff between the economic payoff of fishers and ecological benefits when a
      reserve is established at equal to, or less than, its optimum size.

PMID- 15998491
TI  - Mathematical models for tubular structures in the family of Papovaviridae.
AB  - An important part of a virus is its protein shell, called the viral capsid, that
      protects the viral genome. While the viral capsids of viruses in the family of
      Papovaviridae are usually spherical, their protein building blocks are known to
      assemble also as tubular structures [Kiselev, N.A., Klug, A., 1969. J. Mol. Biol.
      40, 155]. In Twarock [2004. J. Theor. Biol. 226, 477] Viral Tiling Theory has
      been introduced for the structural description of the protein stoichiometry of
      the spherical capsids in this family. This approach is extended here to the
      tubular case and is used to classify the surface lattices of tubular structures
      in the family of Papovaviridae. The predictions of the theory are compared with
      the experimental results in Kiselev and Klug [1969. J. Mol. Biol. 40, 155].

PMID- 15998492
TI  - A model of oxygen uptake kinetics in response to exercise: including a means of
      calculating oxygen demand/deficit/debt.
AB  - We present a new model of the underlying dynamics of the oxygen uptake VO2(v,t)
      kinetics for various exercise intensities. This model is in the form of a set of
      nonlinear coupled vector fields for the VO2(v,t) and v, the derivative of the
      exercise intensity with respect to time. We also present a new and novel means
      for calculating the oxygen demand, D(v,t), and hence also the oxygen deficit and
      debt, given the time series of the VO2(v,t). This enables us to give better
      predictions for these values especially for when exercising at or close to
      maximal exercise intensities. Our model also allows us to predict the oxygen
      uptake time series given the time series for the exercise intensity as well as to
      investigate the oxygen uptake response to nonlinear exercise intensities. Neither
      of these features is possible using the currently used three-phase model. We also
      present a review of both the underlying physiology and the three-phase model.
      This includes for the first time a complete set of the analytical solutions of
      the three-phase model for the oxygen deficit and debt.

PMID- 15998493
TI  - A genetic code Boolean structure. II. The genetic information system as a Boolean
      information system.
AB  - A Boolean structure of the genetic code where Boolean deductions have biological
      and physicochemical meanings was discussed in a previous paper. Now, from these
      Boolean deductions we propose to define the value of amino acid information in
      order to consider the genetic information system as a communication system and to
      introduce the semantic content of information ignored by the conventional
      information theory. In this proposal, the value of amino acid information is
      proportional to the molecular weight of amino acids with a proportional constant
      of about 1.96 x 10(25) bits per kg. In addition to this, for the experimental
      estimations of the minimum energy dissipation in genetic logic operations, we
      present two postulates: (1) the energy Ei (i=1,2,...,20) of amino acids in the
      messages conveyed by proteins is proportional to the value of information, and
      (2) amino acids are distributed according to their energy Ei so the amino acid
      population in proteins follows a Boltzmann distribution. Specifically, in the
      genetic message carried by the DNA from the genomes of living organisms, we found
      that the minimum energy dissipation in genetic logic operations was close to
      kTLn(2) joules per bit.

PMID- 15998494
TI  - Moments of the Boltzmann distribution for RNA secondary structures.
AB  - We here present a dynamic programming algorithm which is capable of calculating
      arbitrary moments of the Boltzmann distribution for RNA secondary structures. We
      have implemented the algorithm in a program called RNA-variance and investigate
      the difference between the Boltzmann distribution of biological and random RNA
      sequences. We find that the minimum free energy structure of biological sequences
      has a higher probability in the Boltzmann distribution than random sequences.
      Moreover, we show that the free energies of biological sequences have a smaller
      variance than random sequences and that the minimum free energy of biological
      sequences is closer to the expected free energy of the rest of the structures
      than that of random sequences. These results suggest that biologically functional
      RNA sequences not only require a thermodynamically stable minimum free energy
      structure, but also an ensemble of structures whose free energies are close to
      the minimum free energy.

PMID- 15998495
TI  - Pollen limitation or mate search need not induce an Allee effect.
AB  - When a process modelling the availability of gametes is included explicitly in
      population models a critical depensation or Allee effect usually results. Non
      spatial models cannot describe clumping and so small populations must be assumed
      very diffuse. Consequently individuals in small populations experience low
      contact rates and so reproduction is limited. In Nature invasions into new
      territory are unlikely to be as diffuse as those described by non-spatial models.
      We develop pair approximations to a probabilistic cellular automata model with
      independent pollination and seed setting processes (equivalently mate search and
      reproduction processes). Each process can be either global (population-wide) or
      local (within a small neighbourhood) or a mixture of the two. When either process
      is global the resulting model recaptures the Allee effect found in non-spatial
      models. However, if both processes are at least partially local we obtain a model
      in which Allee effects can be avoided altogether if individuals are suitably
      strong pollinators and colonisers. The Allee effect disappears because small
      populations are dramatically more clumped when colonisation is local and less
      wasteful of pollen when pollination is local.

PMID- 15998496
TI  - Cats protecting birds revisited.
AB  - In this paper, we revisit the dynamical interaction among prey (bird),
      mesopredator (rat), and superpredator (cat) discussed in [Courchamp, F.,
      Langlais, M., Sugihara, G., 1999. Cats protecting birds: modelling the
      mesopredator release effect. Journal of Animal Ecology 68, 282-292]. First, we
      develop a prey-mesopredator-superpredator (i.e., bird-rat-cat, briefly, BRC)
      model, where the predator's functional responses are derived based on the
      classical Holling's time budget arguments. Our BRC model overcomes several model
      construction problems in Courchamp et al. (1999), and admits richer, reasonable
      and realistic dynamics. We explore the possible control strategies to save or
      restore the bird by controlling or eliminating the rat or the cat when the bird
      is endangered. We establish the existence of two types of mesopredator release
      phenomena: severe mesopredator release, where once superpredators are suppressed,
      a burst of mesopredators follows which leads their shared prey to extinction; and
      mild mesopredator release, where the mesopredator release could assert more
      negative impact on the endemic prey but does not lead the endemic prey to
      extinction. A sharp sufficient criterion is established for the occurrence of
      severe mesopredator release. We also show that, in a prey-mesopredator
      superpredator trophic food web, eradication of introduced superpredators such as
      feral domestic cats in the BRC model, is not always the best solution to protect
      endemic insular prey. The presence of a superpredator may have a beneficial
      effect in such systems.

PMID- 15998497
TI  - A mathematical model for assessing control strategies against West Nile virus.
AB  - Since its incursion into North America in 1999, West Nile virus (WNV) has spread
      rapidly across the continent resulting in numerous human infections and deaths.
      Owing to the absence of an effective diagnostic test and therapeutic treatment
      against WNV, public health officials have focussed on the use of preventive
      measures in an attempt to halt the spread of WNV in humans. The aim of this paper
      is to use mathematical modelling and analysis to assess two main anti-WNV
      preventive strategies, namely: mosquito reduction strategies and personal
      protection. We propose a single-season ordinary differential equation model for
      the transmission dynamics of WNV in a mosquito-bird-human community, with birds
      as reservoir hosts and culicine mosquitoes as vectors. The model exhibits two
      equilibria; namely the disease-free equilibrium and a unique endemic equilibrium.
      Stability analysis of the model shows that the disease-free equilibrium is
      globally asymptotically stable if a certain threshold quantity (R0), which
      depends solely on parameters associated with the mosquito-bird cycle, is less
      than unity. The public health implication of this is that WNV can be eradicated
      from the mosquito-bird cycle (and, consequently, from the human population) if
      the adopted mosquito reduction strategy (or strategies) can make R0<1. On the
      other hand, it is shown, using a novel and robust technique that is based on the
      theory of monotone dynamical systems coupled with a regular perturbation argument
      and a Liapunov function, that if R0>1, then the unique endemic equilibrium is
      globally stable for small WNV-induced avian mortality. Thus, in this case, WNV
      persists in the mosquito-bird population.

PMID- 15998498
TI  - Diffusion and home range parameters from rodent population measurements in
      Panama.
AB  - Simple random walk considerations are used to interpret rodent population data
      collected in Hantavirus-related investigations in Panama regarding the short
      tailed cane mouse, Zygodontomys brevicauda. The diffusion constant of mice is
      evaluated to be of the order of (and larger than) 200 meters squared per day. The
      investigation also shows that the rodent mean square displacement saturates in
      time, indicating the existence of a spatial scale which could, in principle, be
      the home range of the rodents. This home range is concluded to be of the order of
      70 meters. Theoretical analysis is provided for interpreting animal movement data
      in terms of an interplay of the home ranges, the diffusion constant, and the size
      of the grid used to monitor the movement. The study gives impetus to a
      substantial modification of existing theory of the spread of the Hantavirus
      epidemic which has been based on simple diffusive motion of the rodents, and
      additionally emphasizes the importance for developing more accurate techniques
      for the measurement of rodent movement.

PMID- 15998499
TI  - Ovarian and IGF-I axis control of mammary development in prepubertal heifers.
AB  - Although much is known about the endocrine control of bovine mammary development,
      most heifer work has focused on periods near the time of puberty or during
      gestation. However, we have found that ovariectomy in the prepubertal period also
      markedly impacts mammary development well before the onset of estrus would have
      normally occurred. Interactions between the pituitary and ovary to control udder
      development are mediated at least in part via alteration in concentrations of
      local IGF-I axis molecules within the developing mammary gland. For example, in
      heifers treated with growth hormone or estrogen, expression of IGF-I binding
      proteins (IGFBP-3) protein was reduced, thus effecting an increase in free IGF-I.
      Ovariectomized heifers had reduced rates of epithelial cell proliferation, fewer
      IGF-I receptors, and less local IGF-I. Mammary tissue expression of fibronectin
      was increased in ovariectomized heifers, but laminin expression was higher in
      controls. Thus, alterations in specific extracellular matrix proteins likely
      impact heifer mammary development. As a result, we have initiated calfhood
      studies. At 30 days of age, it is difficult to detect parenchymal tissue in the
      udder. Only a thin cord of parenchymal tissue (150 mg per gland) is discernible.
      By 75 days of age, a rounded, walnut-like mass of mammary parenchymal tissue
      becomes very evident and at 90 days of age, this mass of tissue has grown to
      approximately 10 g, a approximately 60-fold increase. At 2 months of age, most
      proliferating epithelial cells (>92%) are confined to a population of light and
      intermediate-staining parenchymal cells. Between 2 and 5 months of age, a dark
      staining cell population markedly emerges, but these dark cells were rarely
      labeled with bromodeoxyuridine (BrdU) and are likely to represent a more
      differentiated or committed cell lineage. The coordinated change in the
      proportions of each cell type suggests a progression from light-, to intermediate
      , to dark-staining cell phenotypes. We are currently focusing on the importance
      of the ovary and mammary tissue synthesis of estrogens on emergence of specific
      populations of putative mammary stem cells.

PMID- 15998500
TI  - Normal and disturbed milk ejection in dairy cows.
AB  - More than 80% of the milk stored in the udder, i.e. the alveolar fraction, only
      available after milk ejection is induced by the release of oxytocin and
      myoepithelial contraction. Milk ejection is induced by tactile teat stimulation,
      either manually or by the milking machine. The time from the start of a tactile
      stimulation until the occurrence of milk ejection spans from 40 s up to more than
      2 min and increases with decreasing degree of udder filling. Therefore, cows need
      a longer pre-stimulation in late stages of lactation or if the milking is
      performed shortly after the previous milking whereas in full udders, pre
      stimulation is less important. Milk ejection can be disturbed under several
      conditions, for example, during milking in unfamiliar surroundings or for several
      weeks after parturition in many primiparous cows. We found that a disturbed milk
      ejection is due to a reduced release or complete absence of oxytocin from the
      pituitary. During milkings with disturbed milk ejection in unfamiliar
      surroundings, the concentrations of cortisol and beta-endorphin were elevated.
      While exogenous glucocorticoids could not induce the disturbance, morphine caused
      inhibition of oxytocin release during milking. However, spontaneously occurring
      disturbance of milk ejection could not be abolished by the opioid-antagonist
      naloxone. On the other hand, severity of disturbed milk ejection and coping
      capacity towards novel milking environment was inversely related to the cortisol
      release in response to ACTH, i.e. adrenal cortex activity. Therefore, the
      susceptibility of individual cows to the inhibition of oxytocin release and milk
      ejection could be predicted by an ACTH challenge test.

PMID- 15998501
TI  - Insulin-like growth factor binding proteins initiate cell death and extracellular
      matrix remodeling in the mammary gland.
AB  - We have demonstrated that insulin-like growth factor binding protein-5 (IGFBP-5)
      production by mammary epithelial cells increases dramatically during forced
      involution of the mammary gland in rats, mice and pigs. We proposed that growth
      hormone (GH) increases the survival factor IGF-I, whilst prolactin (PRL) enhances
      the effects of GH by decreasing the concentration of IGFBP-5, which would
      otherwise inhibit the actions of IGFs. To demonstrate a causal relationship
      between IGFBP-5 and cell death, we created transgenic mice expressing IGFBP-5,
      specifically, in the mammary gland. DNA content in the mammary glands of
      transgenic mice was decreased as early as day 10 of pregnancy. Mammary cell
      number and milk synthesis were both decreased by approximately 50% during the
      first 10 days of lactation. The concentrations of the pro-apoptotic molecule
      caspase-3 was increased in transgenic animals whilst the concentrations of two
      pro-survival molecules Bcl-2 and Bcl-x were both decreased. In order to examine
      whether IGFBP-5 acts by inhibiting the survival effect of IGF-I, we examined IGF
      receptor- and Akt-phoshorylation and showed that both were inhibited. These
      studies also indicated that the effects of IGFBP-5 could be mediated in part by
      IGF-independent effects involving potential interactions with components of the
      extracellular matrix involved in tissue remodeling, such as components of the
      plasminogen system, and the matrix metallo-proteinases (MMPs). Mammary
      development was normalised in transgenic mice by R3-IGF-I, an analogue of IGF-I
      which binds weakly to IGFBPs, although milk production was only partially
      restored. In contrast, treatment with prolactin was able to inhibit early
      involutionary processes in normal mice but was unable to prevent this in mice
      over-expressing IGFBP-5, although it was able to inhibit activation of MMPs.
      Thus, IGFBP-5 can simultaneously inhibit IGF action and activate the plasminogen
      system thereby coordinating cell death and tissue remodeling processes. The
      ability to separate these properties, using mutant IGFBPs, is currently under
      investigation.

PMID- 15998502
TI  - Ovarian function in ruminants.
AB  - The purpose of this overview is to highlight important steps of ovarian
      regulation during follicle development, ovulation and the life span of corpus
      luteum (CL) in ruminants. The ovarian cycle is central to reproductive function.
      It is characterized by repeating patterns of cellular proliferation,
      differentiation and transformation that encompass follicular development and
      ovulation as well as the formation, function and regression of the CL. In the
      first part, the importance and regulation of final follicle growth and especially
      of angiogenesis and blood flow during folliculogenesis, dominant follicle
      development and CL formation are described. Our results underline the importance
      of growth factors especially of insulin-like growth factor (IGF), vascular
      endothelial growth factor (VEGF) and fibroblast growth factor (FGF) for
      development and completion of a dense network of capillaries (angiogenesis)
      during follicle growth and CL formation. In the second part, the regulation of CL
      function by endocrine/paracrine and autocrine acting regulators is discussed.
      There is evidence that besides the main endocrine hormones luteinizing hormone
      (LH) and growth hormone (GH) local regulators as growth factors, peptides,
      steroids and prostaglandins are important modulators of luteal function. During
      early CL development until midluteal stage oxytocin (OT), prostaglandins and
      progesterone (P) itself stimulate luteal cell proliferation and function
      supported by the luteotropic action of a number of growth factors. The still high
      mRNA expression, protein concentration and localization of VEGF, FGF and IGF
      family members in the cytoplasm of luteal cells during midluteal stage suggest
      that they play pivotal role in the maintenance (survival) of this endocrine
      tissue. The major function of the CL is to secrete P. Progesterone itself
      regulates the length of the estrous cycle via influencing the timing of the
      luteolytic PGF2alpha signal from the endometrium. At the end of a nonfertile
      cycle, the regression of CL commences, steroidogenic capacity is lost (functional
      luteolysis), cell death is initiated, and tissue involution as well as resorption
      occurs within a few days (structural luteolysis). The cascade of mediators during
      luteolysis is very complex and still awaits elucidation. Evidence is given for
      participation of blood flow, inflammatory cytokines, vasoactive peptides
      (angiotensin II and endothelin-1), and decrease of the classical luteotropic
      mediators.

PMID- 15998503
TI  - Factors regulating ovarian function in pigs.
AB  - The hormonal interactions of the hypothalamic-pituitary-ovarian-uterine axis are
      accountable for a normal reproduction in female pigs. It is of importance to have
      knowledge of estrous symptoms and hormonal profiles around ovulation. The
      introduction of the transrectal ultrasonography in sows has given us the
      possibility to study ovarian activity in conscious animals and relate the timing
      of estrus to ovulation. Combining this technique with measuring of several
      hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      inhibin, estradiol, progesterone, insulin-like growth hormone I (IGF-I),
      prostaglandin F2alpha (PGF2alpha) metabolite, oxytocin, facilitate our knowledge
      about the sequence of ovarian events. Evidence suggests that activation of the
      hypothalamic-pituitary-adrenal axis may hamper the normal gonadotropin secretion
      and in consequence, the ovarian function. The metabolic status during lactation,
      weaning of piglets and social stress might affect onset of ovarian activity and
      the related estrous behavior. The role of seminal plasma, artificial insemination
      and presence of the boar might also be included as factors regulating the
      temporal kinetics of ovulation, corpus luteum development, uterine function and
      steroid production in the ovary. Studies using a simulated stress by means of
      adrenocorticotrophic hormone (ACTH) administration or food deprivation are tools
      in understanding how the ovary is susceptible to impairment. The intention of
      this paper is to review current knowledge concerning the endocrine aspects of
      normal and stress-influenced ovarian function in pigs.

PMID- 15998504
TI  - Recruitment and selection of ovarian follicles for determination of ovulation
      rate in the pig.
AB  - Gonadotropins determine the follicle selection and ovulation rate. Follicle
      growth is independent of gonadotropins until antrum formation, at which time
      recruitment occurs. Once recruited, follicles will continue to grow or
      degenerate. In gilts, visible surface follicles are classified as small (<3mm),
      medium (3-6.9 mm) and large (> or =7.0mm). At estrus (day 0), there are
      approximately 15 small and medium follicles, and approximately 15 large
      follicles. By day 3, there may be approximately 30 small, 5 medium and no large
      follicles. During the remainder of the luteal phase, the pool of follicles
      increases and peaks at day 11-13 with approximately 50 small, and 30 medium, but
      with no large follicles observed. By the start of the follicular phase at day 15,
      numbers of small and medium follicles rapidly decline, while a pool of medium
      follicles is selected for the ovulation. The size of large follicles at estrus is
      heterogeneous (6.5-10.0 mm) but their number is reflective of the subsequent
      number of corpora lutea found following the ovulation. However, the time of
      medium follicle selection for ovulation is variable during the late luteal and
      early follicular phases. Suppression of FSH before and at the time of luteolysis
      reduces medium and large follicles but does not reduce the ovulation rate. In
      contrast, suppression of FSH for 3 days or unilateral ovariectomy after 3 days of
      the follicular phase prevents full ovulatory compensation. Therefore, FSH appears
      to be involved in the maintenance of a pool of medium follicles that can be
      selected by LH to mature and ovulate.

PMID- 15998505
TI  - Susceptibility of reproduction in female pigs to impairment by stress or
      elevation of cortisol.
AB  - It is generally agreed that stress can impair reproduction. Furthermore, it is
      often thought that cortisol, which is secreted during stress as a result of
      activation of the hypothalamo-pituitary adrenal axis, is associated with this
      stress-induced impairment of reproduction. It has been hypothesized that
      reproduction in females is particularly susceptible to disruption by acute stress
      during the series of endocrine events that induce estrus and ovulation.
      Nevertheless, we found no support for this conjecture when we subjected female
      pigs to repeated acute stress or repeated acute elevation of cortisol during the
      period leading up to estrus and ovulation. Conversely, studies have demonstrated
      that prolonged stress and sustained elevation of cortisol can disrupt
      reproductive processes in female pigs. Nevertheless, in each study that
      demonstrated this effect, there were some animals subjected to the prolonged
      stressor or the sustained elevation of cortisol in which the reproductive
      parameters that were measured were not affected by the treatment. We propose that
      reproduction in female pigs is resistant to the effects of acute or repeated
      acute stress or acute or repeated acute elevation of cortisol even if these occur
      during the series of endocrine events that induce estrus and ovulation.
      Furthermore, while reproductive processes in some individuals are compromised,
      reproduction in a proportion of female pigs appears to be resistant to the
      effects of prolonged stress or sustained elevation of cortisol.

PMID- 15998506
TI  - Consequences of endocrine disrupting chemicals on reproductive endocrine function
      in birds: establishing reliable end points of exposure.
AB  - It has been difficult to establish reliable indices of exposure to endocrine
      disrupting chemicals (EDCs) appropriate for a variety of avian species because of
      a vast array of reproductive strategies. Data from mammals, reptiles and fish
      provide insight on likely mechanisms of action for EDCs. However, many of the
      effects of EDCs are weaker than the actions of the native hormones, making it
      difficult to assess adverse effects in domestic and wild birds. It is clear that
      differential sensitivity to EDCs exists across species, due to the timing and
      mode of exposure, compound toxicity and age of the individual. Our studies on
      EDCs are conducted in the quail model system, with focus on reproductive
      endocrine, neuroendocrine and behavioral responses. Studies have included EDC
      exposure, either by egg injection or via diet. Results from egg injection studies
      showed the following: (1) estradiol administered by embryonic day 12
      demasculinized male sexual behavior, altered hypothalamic neurotransmitters and
      reduced hen day production and fertility in a dose dependent fashion, (2)
      methoxychlor (MXC) or vinclozolin impaired male sexual behavior in adult quail
      and (3) DDE exposure impaired reproductive and immune related end points. Two
      generation studies were conducted on Japanese and northern bobwhite quail with
      dietary methoxychlor (MXC) exposure (0, 5 and 10 ppm) beginning in adults (P1),
      continuing in their offspring (F1), with F2 offspring raised on control diet. MXC
      exposure impaired male sexual behavior, hypothalamic catecholamines and plasma
      steroid hormones. Moreover, MXC exposure had reproductive consequences observable
      at both the lower and higher doses of MXC in F1 and F2 generations. These data
      demonstrate that embryonic EDC exposure interferes with sexual differentiation of
      neural systems that direct reproduction.

PMID- 15998507
TI  - Impact of endocrine disrupting chemicals on reproduction in Japanese quail.
AB  - Many environmental contaminants can interact with the endocrine system, thereby
      potentially disrupting the reproductive fitness of individuals. In avian species,
      the egg-yolk is a major route for excretion of lipophilic compounds by the adult
      female bird and embryos are exposed to contaminants that have been deposited in
      the eggs. The reproductive and neuroendocrine system of Japanese quail undergoes
      sexual differentiation during embryo development. The phenotypic sex, including
      sex-specific adult behavior, is hormonally imprinted already before hatching. The
      sexual differentiation of the brain in quail is sensitive to estrogens and the
      presence of estrogen results in a female phenotype. The relatively low
      concentration of estrogens in male embryos, on the other hand, results in a male
      behavioral phenotype. The behavior of male quail can be demasculinized by
      estrogen exposure during the period of sexual differentiation, and estrogen
      exposed males are not able to display a male-typical behavior as adults. Also,
      differentiation of the reproductive organs is sensitive to hormones during
      embryogenesis, and an excess of estrogens can for instance induce persistent
      morphological changes in the reproductive organs of females. Our research has
      focused on effects in adult birds after embryonic estrogen exposure. We have
      studied sexual behavior and other reproductive variables in adult quail after in
      ovo injection of known and suspected estrogenic compounds. Synthetic estrogens
      and insecticides, such as o,p'-DDT altered the development of the neural system
      and resulted in demasculinization of male quail. In females, o,p'-DDT caused
      morphological changes of the oviduct and egg laying was reduced. Our studies
      suggest that the neural system and the female reproductive system of avian
      embryos are very sensitive to the effects of chemicals with estrogenic activity.

PMID- 15998508
TI  - Relationship of resilience to personality, coping, and psychiatric symptoms in
      young adults.
AB  - Developing a comprehensive understanding of resilience across the lifespan is
      potentially important for mental health promotion, yet resilience has been vastly
      understudied compared to disease and vulnerability. The present study
      investigated the relationship of resilience to personality traits, coping styles,
      and psychiatric symptoms in a sample of college students. Measures included the
      Connor-Davidson Resilience Scale, NEO Five Factor Inventory, Coping Inventory for
      Stressful Situations, and Brief Symptom Inventory. Results supported hypotheses
      regarding the relationship of resilience to personality dimensions and coping
      styles. Resilience was negatively associated with neuroticism, and positively
      related to extraversion and conscientiousness. Coping styles also predicted
      variance in resilience above and beyond the contributions of these personality
      traits. Task-oriented coping was positively related to resilience, and mediated
      the relationship between conscientiousness and resilience. Emotion-oriented
      coping was associated with low resilience. Finally, resilience was shown to
      moderate the relationship between a form of childhood maltreatment (emotional
      neglect) and current psychiatric symptoms. These results augment the literature
      that seeks to better define resilience and provide evidence for the construct
      validity of the Connor-Davidson Resilience Scale.

PMID- 15998509
TI  - Distribution of breast cancer resistance protein (BCRP/ABCG2) mRNA expression
      along the human GI tract.
AB  - Human breast cancer resistance protein (BCRP/ABCG2) is an ABC-transporter that is
      present on the luminal membrane of intestinal epithelial cells and restricts
      absorption of anticancer drugs such as methotrexate, topotecan, mitoxantrone, and
      doxorubicin. The exact anatomic distribution of BCRP along the gastrointestinal
      (GI) tract, however, has not been determined before. The aim of this study was,
      therefore to investigate BCRP mRNA expression pattern along the GI tract in 14
      healthy subjects. Furthermore, BCRP duodenal mRNA expression was compared with
      MDR1/ABCB1 mRNA. Additionally, BCRP mRNA expression was investigated in two human
      intestinal cell lines (Caco-2 and LS180). Since previous animal studies have
      suggested sex specific differences in BCRP expression, we analyzed intestinal
      BCRP expression with respect to sex. Biopsies were taken from different gut
      segments (duodenum, terminal ileum and ascending, transverse, descending and
      sigmoid colon). Gene expression was assessed by quantitative real-time PCR
      (Taqman). BCRP mRNA expression was maximal in the duodenum and decreased
      continuously down to the rectum (terminal ileum 93.7%, ascending colon 75.8%,
      transverse colon 66.6%, descending colon 62.8%, and sigmoid colon 50.1% compared
      to duodenum, respectively). BCRP expression in the duodenum was comparable to
      MDR1/ABCB1 gene expression. Caco-2 cells showed a comparable expression of BCRP
      as human duodenal tissue. Gender specific differences in BCRP expression were not
      observed. These findings represent the first systematic site-specific analysis of
      BCRP expression along the GI tract. This information might be helpful to develop
      target strategies for orally administered anticancer drugs.

PMID- 15998510
TI  - Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide
      synthase by phenolic (3E)-4-(2-hydroxyphenyl)but-3-en-2-one in RAW 264.7
      macrophages.
AB  - The large amount of nitric oxide (NO) produced by inducible NO synthase (iNOS)
      contributes to cellular injury in inflammatory disease. In the present study, a
      novel synthetic compound (3E)-4-(2-hydroxyphenyl)but-3-en-2-one (HPB) was found
      to inhibit lipopolysaccharide (LPS)-induced NO generation, but not through the
      inhibition of iNOS activity, in RAW 264.7 macrophages. Administration of HPB into
      mice also inhibited the LPS-induced increase in serum nitrite/nitrate levels. To
      evaluate the underlying mechanisms of HPB inhibition of NO generation, the
      expression of the iNOS gene in RAW 264.7 macrophages was examined. HPB abolished
      the LPS-induced expression of iNOS protein, iNOS mRNA and iNOS promoter activity
      in a similar concentration-dependent manner. LPS-induced nuclear factor-kappaB
      (NF-kappaB) DNA binding and NF-kappaB-dependent reporter gene activity were both
      significantly inhibited by HPB. This effect was mediated through the inhibition
      of inhibitory factor-kappaBalpha (IkappaBalpha) phosphorylation and degradation,
      and of p65 nuclear translocation. HPB had no effect on the LPS-induced
      phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen
      activated protein kinases (MAPK), and c-Jun NH(2)-terminal kinase (JNK). However,
      HPB suppressed the LPS-induced intracellular reactive oxygen species (ROS)
      production. These results indicate that HPB down-regulates iNOS gene expression
      probably through the inhibition of LPS-induced intracellular ROS production,
      which has been implicated in the activation of NF-kappaB.

PMID- 15998511
TI  - Communication during trauma resuscitation: do we know what is happening?
AB  - OBJECTIVE: Verbal communication is essential for teamwork and leadership in high
      intensity performances like trauma resuscitation. We evaluated communication
      during multidisciplinary trauma resuscitation. METHODS: The main trauma room of a
      level one trauma centre was equipped with a digital video recording system.
      Resuscitations were consecutively and prospectively enrolled. Patients with
      revised trauma score (RTS)=12 were resuscitated by a 'minor trauma team' and
      patients with RTS<12 by a 'major trauma team'. Information transferral from
      physicians to other team members was evaluated separately for all ABCDE's,
      according to initiation, audibility and response. The observer was trained and
      the first 30 video's were excluded. RESULTS: From May 1st to September 1st 2003,
      205 resuscitations were included, 12 were lost for evaluation. The 'major trauma
      team' resuscitated 74 patients (ISS:21.4). Communication was audible in 56% and
      understandable in 44% during the primary survey. The 'minor trauma team' assessed
      119 patients (ISS:7.4). Communication was audible in 43% and understandable in
      33%. CONCLUSIONS: Communication during trauma resuscitation was found to be sub
      optimal. This is potentially harmful for trauma victims. Professionals and
      institutions should be aware that communication is not self-evident. Introduction
      of an aviation-like communication feedback system could help to optimise trauma
      care.

PMID- 15998512
TI  - Psychosocial aspects of road traffic trauma--benefits of an early intervention?
AB  - PURPOSE: To assess the psychosocial consequences of traffic accidents, and to
      evaluate the effect of an intervention programme to reduce the occurrence and
      extent of psychosocial residual states. MATERIAL AND METHODS: A telephone
      interview was conducted with 314 individuals, 1(1/2)-2 years after the accident
      in 1994-1995. The effect of the intervention programme was studied for
      inpatients, 68 in the study group, and 89 in the control group. The structured
      follow-up form included the Impact of Event Scale (IES). RESULTS: Half of those
      injured had residual physical complaints with negative effects on their work- and
      economic-situation. An influence on housing or the need for practical assistance
      was reported by 1-7%. Mental effects were reported by 4/5. IES demonstrated that
      1/5 suffered a high degree of intrusion, and this occurred twice as often among
      females as among males. Situational anxiety occurred more often in the
      intervention group than in the control group, p=0.02. More individuals in the
      intervention group than in the control group were satisfied with the medical
      certificate to the insurance company, p=0.058. CONCLUSIONS: Females were
      afflicted by mental effects considerably more than males. The intervention
      programme did not appear to reduce the psychosocial sequelae. The methods within
      this area need to be further developed.

PMID- 15998513
TI  - Enhanced neutrophil migratory activity following major blunt trauma.
AB  - BACKGROUND: Neutrophil migration into the lung is a critical, but poorly
      understood step in the pathogenesis of post-traumatic, acute respiratory distress
      syndrome (ARDS). We investigated changes in interleukin-8 (IL-8) mediated
      neutrophil migration and associated changes in receptor expression, of the IL-8
      receptors CXCR1, the integrins CD11b/CD18 and platelet endothelial cell adhesion
      molecule-1 (PECAM-1) in patients sustaining major trauma. METHODS: Eleven
      patients with major trauma, injury severity score (ISS), median 22 (range 18-41),
      were followed prospectively. Eleven normal volunteers were used as controls.
      Blood samples were obtained within 4+/-2 h of injury, at 24 h, day 3 and day 5.
      Neutrophils migration was assessed by an in vitro IL-8 assay and neutrophil
      surface receptor expression by FACS analysis. RESULTS: IL-8 mediated neutrophil
      migration was significantly increased on admission following major trauma and
      remained elevated for 3 days (p<0.05). This was associated with up-regulation of
      CXCR1 (p<0.01) and down-regulation of PECAM-1 (p<0.05). CD11b and CD18 although
      initially unchanged, became down-regulated on day 3 (p<0.05). CONCLUSIONS: These
      data show that major trauma primes circulating neutrophils for increased
      migration in response to IL-8. This response is sustained for 72 h and is
      associated with changes in neutrophil surface receptor expression.

PMID- 15998514
TI  - Immediate impact of 'penalty points legislation' on acute hospital trauma
      services.
AB  - Road traffic accident (RTA) related mortality and injury may be reduced by up to
      40% with the introduction of 'road safety' legislation. Little is known regarding
      changes in pattern of injury and overall resource impact on acute trauma
      services. This prospective study examines RTA related admissions, injuries
      sustained and resultant sub-speciality operative workload in a Level 1 Trauma
      Centre during the 12 months immediately prior to and following the introduction
      of 'penalty points' legislation. Eight hundred and twenty RTA related admissions
      were identified over the 24-month period from 01/11/2001 to 31/10/2003. There was
      a 36.7% decrease in RTA related admissions subsequent to the introduction of new
      legislation. Bed occupancy was almost halved. However, the relative Orthopaedic
      workload increased from 34% to 41% with a 10% increase in relative bed occupancy.
      The pattern of orthopaedic injury was significantly altered with a >50% absolute
      reduction in high velocity injuries. Curiously, there was no change in the
      absolute number of spinal fractures seen. This favourable early Irish experience
      of 'penalty points' legislation mirrors that of worldwide published literature.
      Our findings demonstrate that the injury reduction effects were primarily enjoyed
      by non-orthopaedic sub-specialities. Such findings mandate consideration when
      allocating vital resources to sub-specialities within busy trauma units.

PMID- 15998515
TI  - Vaccination with recombinant Ascaris suum 24-kilodalton antigen induces a Th1/Th2
      mixed type immune response and confers high levels of protection against
      challenged Ascaris suum lung-stage infection in BALB/c mice.
AB  - Previous studies have shown that antigens from various life-cycle stages of
      Ascaris suum can induce host-protective immunity against challenge infections
      with infective eggs of A. suum. This study evaluated whether Escherichia coli
      expressed recombinant 24-kDa antigen from A. suum (rAs24) was a suitable vaccine
      candidate for the control of Ascaris infections by examining its performance in a
      mouse model. Immunization of BALB/c mice in three consecutive doses with rAs24 in
      Freund's Complete Adjuvant (FCA) results in protection against challenge
      infections as manifested by a 58% reduction (P<0.001) in recovery and stunted
      development of A. suum lung-stage larvae at day 7 post-challenge. Sera obtained
      from immune protected mice had a significantly increased level of immunoglobulin
      G (IgG) (P<0.0001) but had no IgE response. Analysis of IgG-subclass profiles
      revealed that IgG1 (P<0.0001) showed the greatest increase followed by IgG2b
      (P<0.005), IgG2a (P<0.006) and IgG3 (P<0.04). Splenic T cells from rAs24-FCA
      immunized mice secreted significantly high levels of both Th1 cytokine gamma
      interferon (P<0.005) and Th2 cytokine interleukin-10 (P<0.001) after stimulation
      with rAs24 in vitro. Interestingly, affinity purified anti-rAs24 IgG was shown to
      inhibit moulting of A. suum lung-stage L3 to L4 in vitro by 26%, indicating an in
      vivo function of the endogenous As24 in the moulting processes. An intense
      expression of endogenous As24 in the hypodermis and gut epithelium of A. suum
      lung-stage L3 by immunofluorescence supports a function for endogenous As24.
      These findings may contribute to the understanding of rAs24-induced Th1/Th2
      mediated effector mechanisms required for the protection of A. suum lung-stage
      larval infection.

PMID- 15998516
TI  - Echinococcus multilocularis in red foxes (Vulpes vulpes) of the Italian Alpine
      region: is there a focus of autochthonous transmission?
AB  - Alveolar echinococcosis, caused by the metacestode of Echinococcus
      multilocularis, is a zoonosis with a wider distribution area than described in
      the past. Fox populations living in the Alpine regions of Italy had been
      considered free from this parasite until 2002, when two infected foxes (Vulpes
      vulpes) were detected in the Bolzano province (Trentino Alto Adige region) near
      the Austrian border. The aim of this work was to evaluate the prevalence of
      infection in red fox populations from five Italian regions. A modified nested PCR
      analysis was used to detect E. multilocularis DNA in faecal samples. Amplicons
      were confirmed by sequencing. Of 500 faecal samples from foxes shot in Valle
      d'Aosta (n=57), Liguria (n=44), Lombardy (n=102), Veneto (n=56), and Trentino
      Alto Adige (n=241) regions, 24 animals, all from the Trentino Alto Adige region,
      were found positive. Twenty-two positive animals originated from the Bolzano
      province and two positive animals from the Trento province. Several localities of
      the Bolzano province, in which positive foxes were detected, are the same as
      those where alveolar echinococcosis had been described in humans in the second
      half of the 19th century, suggesting an old endemicity for the investigated area,
      which is adjacent to endemic areas of Austria. Therefore, the question arises if
      we are observing an increase and expansion of foci, or if the new records are due
      to the more sensitive and specific methods used to detect the worm DNA.

PMID- 15998517
TI  - Plasma levels of oxidized-low-density lipoproteins are higher in patients with
      unstable angina and correlated with angiographic coronary complex plaques.
AB  - OBJECTIVES: To measure circulating levels of oxidized-low-density lipoproteins
      (ox-LDL) in patients with stable and unstable angina and controls, and to
      investigate their correlation with the extent of coronary artery disease (CAD)
      and the presence of complex plaques at coronary angiography. METHODS AND RESULTS:
      Circulating ox-LDL were assessed, using ELISA, in patients with unstable angina
      (UA, n=26), stable angina (SA, n=29) and in controls (C, n=27). All patients
      underwent coronary angiography. The extent of CAD was evaluated using a
      quantitative score, while the presence of complex, vulnerable plaques was
      angiographically assessed. Ox-LDL were higher in UA patients than in SA patients
      and in C subjects, and in SA patients than in C subjects (C, 45.6+/-12.8 U/L; SA,
      58.8+/-11.0 U/L; UA, 73.7+/-13.6 U/L; p<0.001). No correlation was found with the
      extent of atherosclerotic disease in the coronary tree. Patients with
      angiographic complex lesions showed significantly higher levels of ox-LDL (68.4+/
      13.9 U/L versus 55.2+/-16.4 U/L, p<0.001). Multiple regression analysis showed
      that ox-LDL were independent predictors of the presence of complex plaques
      (p<0.023). CONCLUSIONS: Ox-LDL levels are higher in unstable patients and
      correlate with the presence of angiographically documented complex plaques. Ox
      LDL might be markers of destabilization of CAD.

PMID- 15998518
TI  - Appraisal of the extent of chronic allograft vasculopathy in animal models:
      proposition of a standardized micromorphometric method.
AB  - Arterial obstruction due to intimal myproliferation is an outcome used for
      investigating chronic allograft vasculopathy in animal models. Since harvested
      tissue may be distorted while processing, discrepancy may happen in the measure
      of the obstruction. We propose a standardized micromorphometric method for
      calculating the percentage of obstruction with eliminating the variability in the
      shape of the vessel cross-section. The mathematical adjustment avoids the
      overestimation of the percentage of obstruction and improves accuracy.

PMID- 15998519
TI  - Anti-TNF therapy and plasma HDL cholesterol concentration.

PMID- 15998520
TI  - Changes in aortic endothelial gene expressions and relaxation responses following
      chronic short-term insulin treatment in diabetic rats.
AB  - The purpose of the present study was to examine the relationship between the
      changes in the expressions of several mRNAs and changes in endothelial function
      in streptozotocin-induced diabetic and chronic short-term insulin-treated rats.
      Aortas from later-stage (10 week) diabetics, but not those from their insulin
      treated counterparts, showed an impaired endothelial function. We found that the
      mRNA expressions for 30 genes were significantly upregulated, while those for 13
      other genes were downregulated in aortic endothelial cells from diabetes. In
      later-stage diabetes, chronic insulin treatment ameliorated the endothelial
      dysfunction and normalized the expressions for 20 out of the 43 genes altered in
      diabetes. Further, 12 of the remaining 23 genes were altered by high-dose insulin
      treatment in the controls. In early-stage (1 week) diabetic aortas, which did not
      show impaired endothelial function, expression changes were shown by only 12/30
      and 5/13 of the genes up- or downregulated, respectively, in later-stage
      diabetes. Thus, in the diabetic aortas endothelial gene expressions and function
      exhibited time-related changes, and several gene expressions and endothelial
      function were normalized by insulin treatment. The hyperinsulinemia caused by
      this treatment may oppose the alterations in some gene expressions and the
      endothelial proliferation (cell growth-related gene expressions) that occur in
      established diabetes.

PMID- 15998521
TI  - Atorvastatin induces insulin sensitization in Zucker lean and fatty rats.
AB  - BACKGROUND: The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase
      inhibitors ('statins') have been implicated in preventing new onset type 2
      diabetes, whereas the mechanism of this effect is not known. We investigated the
      effects of an HMG-CoA reductase inhibitor, atorvastatin, on insulin sensitization
      in Zucker lean and fatty rats. METHODS AND RESULTS: In vivo studies of insulin
      sensitization were performed in chow fed Zucker lean and fatty rats treated with
      atorvastatin 50mg/kg/day (ATORVA_50) and results were compared to Zucker lean and
      fatty rats treated with drug vehicle only (CONT). Additional Zucker lean rats
      were treated with an intermediate dose of atorvastatin 25mg/kg/day (ATORVA_25).
      Treatment with atorvastatin resulted in a dose-dependent improvement in whole
      body insulin sensitivity in both lean and fatty rats, with an approximately two
      fold increase in glucose infusion rate and glucose disposal (Rd) in ATORVA_50
      versus CONT (p<0.01). Atorvastatin 50mg/kg/day resulted in an increase in 2
      deoxyglucose (2-DOG) uptake by skeletal muscles (approximately two-fold increase
      in 2-DOG uptake in quadriceps (p=0.06) and gastrocnemius (p<0.01)) in lean Zucker
      rats. Insulin-stimulated phosphorylation of Akt/PKB was significantly increased
      in skeletal muscle of ATORVA_50 versus CONT in both lean and fatty rats.
      CONCLUSION: Atorvastatin induces insulin sensitization in Zucker lean and fatty
      rats. This may be a clinically important pleiotropic effect if confirmed in
      insulin resistant humans.

PMID- 15998522
TI  - Calibration of a Hall effect displacement measurement system for complex motion
      analysis using a neural network.
AB  - Biomechanics studies often require the analysis of position and orientation.
      Although a variety of transducer and camera systems can be utilized, a common
      inexpensive alternative is the Hall effect sensor. Hall effect sensors have been
      used extensively for one-dimensional position analysis but their non-linear
      behavior and cross-talk effects make them difficult to calibrate for effective
      and accurate two- and three-dimensional position and orientation analysis. The
      aim of this study was to develop and calibrate a displacement measurement system
      for a hydraulic-actuation joystick used for repetitive motion analysis of heavy
      equipment operators. The system utilizes an array of four Hall effect sensors
      that are all active during any joystick movement. This built-in redundancy allows
      the calibration to utilize fully connected feed forward neural networks in
      conjunction with a Microscribe 3D digitizer. A fully connected feed forward
      neural network with one hidden layer containing five neurons was developed.
      Results indicate that the ability of the neural network to accurately predict the
      x, y and z coordinates of the joystick handle was good with r(2) values of 0.98
      and higher. The calibration technique was found to be equally as accurate when
      used on data collected 5 days after the initial calibration, indicating the
      system is robust and stable enough to not require calibration every time the
      joystick is used. This calibration system allowed an infinite number of joystick
      orientations and positions to be found within the range of joystick motion.

PMID- 15998523
TI  - Expression of p53 in renal carcinoma cells is independent of pVHL.
AB  - Renal clear-cell carcinoma (RCC) is the predominant form of kidney cancer and is
      highly refractory to conventional anti-cancer therapies. The status of p53 tumor
      suppressor gene has been correlated with the efficacy of radio- and
      chemotherapies, where presence of mutant p53 is associated with reduced
      responsiveness to treatment. However, p53 itself is rarely mutated in RCC, rather
      suggesting that the p53 pathway might be compromized in RCC cells. In support of
      this notion, the transactivation property of normal p53 was shown to be repressed
      in various transformed kidney epithelial cells via an unknown dominant-negative
      mechanism. Mutation of the von Hippel-Lindau (VHL) gene causes familial VHL
      disease, which includes predisposition to RCC. Moreover, biallelic inactivation
      of VHL has been observed in the vast majority of sporadic RCC. Recently, the
      expression of pVHL in RCC cells was demonstrated to elevate the expression of p53
      by inducing the binding of RNA-stabilizing protein HuR to the 3'untranslated
      region of p53 mRNA. Contrary to this finding, we report here that the
      reconstitution of a variety of VHL(-/-) RCC lines including 786-O, RCC4, and A498
      or non-RCC cells with wild-type pVHL does not influence the expression of p53 and
      fails to induce p53-responsive gene p21CIP1/WAF1 or p53-responsive reporters.
      These results suggest that the expression of p53 in RCC cells is independent of
      pVHL.

PMID- 15998524
TI  - Involvement of an increased spinal TRPV1 sensitization through its up-regulation
      in mechanical allodynia of CCI rats.
AB  - Vanilloid receptor 1 (TRPV1) antagonists are known to attenuate the neuropathic
      pain symptoms in peripheral nerve injury models, but the mechanism(s) of their
      effect remains unclear. At the same time, the role of spinal TRPV1 in pain
      transduction system has not been fully understood. In this study, the role of
      spinal TRPV1 in mechanical allodynia in rat chronic constriction injury (CCI)
      model was investigated. Intrathecal administration of a selective TRPV1
      antagonist, N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropryazine
      1(2H)-carbox-amide (BCTC) significantly attenuated mechanical allodynia in CCI
      rats at 100 and 300 nmol. In vitro, BCTC inhibited capsaicin (300 nM)-induced
      releases of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and
      substance P-like immunoreactivity (SP-LI) from the rat spinal cord slice
      preparations with IC(50)s of 37.0 and 36.0 nM, respectively, confirming that BCTC
      potently inhibits TRPV1 function in the rat spinal cord. TRPV1 expression levels
      in the spinal cord following CCI were quantified in by Western blot analysis.
      TRPV1 protein levels were significantly increased in the ipsilateral side of the
      lumbar spinal cord at 7 and 14 days following CCI surgery, but not in the
      contralateral side. Furthermore, capsaicin (300 nM)-evoked release of CGRP-LI was
      significantly higher in the ipsilateral spinal cord of CCI rats (14 days after
      surgery) than that of sham-operated rats. These findings suggest that an
      increased sensitization of the spinal TRPV1 through its up-regulation is involved
      in the development and/or maintenance of mechanical allodynia in rat CCI model.

PMID- 15998525
TI  - Group II and III mGluRs-mediated presynaptic inhibition of EPSCs recorded from
      hippocampal interneurons of CA1 stratum lacunosum moleculare.
AB  - We have studied the effects of groups II and III metabotropic glutamate receptor
      (mGluR) activation on excitatory responses recorded from hippocampal interneurons
      of CA1 stratum lacunosum moleculare (SLM). Excitatory postsynaptic currents
      (EPSCs) evoked by stimulation of the perforant pathway were reduced either by the
      group II mGluR agonist LY354740 (50-100 nM, 49.1+/-5.7% of control) or by the
      group III mGluR agonist l-2-amino-4-phosphonobutyric acid (l-AP4) (50 microM,
      36.8+/-4.4% of control). Both drugs significantly enhanced paired-pulse
      facilitation of the EPSCs. Furthermore, both 100 nM LY354740 and 50 microM l-AP4
      reduced the frequency, but not the amplitude, of miniature excitatory synaptic
      currents (mEPSCs), recorded in the presence of 1 microM TTX and 50 microM
      picrotoxin, or EPSCs evoked by perforant pathway stimulation in the presence of
      2.5 mM Sr2+. The broad-spectrum mGluR antagonist LY341495 (10-50 microM) did not
      affect test EPSCs elicited 210 ms after stimulation at 100 Hz. At network level,
      1-5 microM LY354740 significantly reduced the power of gamma frequency
      oscillations induced by 20 microM carbachol, 600 nM kainate and 5 mM K+ in
      hippocampal CA1 area. Our results show powerful modulation of excitatory
      transmission impinging on interneurons of CA1 SLM by presynaptic group II or III
      mGluRs.

PMID- 15998526
TI  - Neuroprotective effect of zVAD against the neurotoxin 3-nitropropionic acid
      involves inhibition of calpain.
AB  - The contribution of calpains and caspases to cell death has been widely studied
      using pharmacological inhibitors. Among them, the caspase inhibitor N
      benzyloxycarbonyl-valyl-alanyl-aspartyl-fluoromethylketone (zVAD) has been used
      as a specific caspase inhibitor in nearly 1000 published studies. However,
      several studies showed that zVAD also behaves as a calpain inhibitor in
      peripheral cells. The effects of zVAD as a calpain inhibitor have never been
      assessed in neurodegeneration models. We examined here whether zVAD could reduce
      neurodegeneration in Huntington's disease models using the mitochondrial
      inhibitor 3-nitropropionic acid (3NP). In these models, 3NP toxicity has been
      shown to require calpain activation. In rats, intra-cerebro-ventricular infusion
      of zVAD significantly reduced 3NP-induced striatal degeneration, and decreased
      the 3NP-induced activation of calpain and calpain-dependent cleavage of fodrin.
      zVAD (100 microM) also blocked 3NP-induced death of cultured striatal neurons. In
      vitro, zVAD inhibited purified mu-calpain with high affinity (IC50=10 nM). The
      present data demonstrate that zVAD protects neurons against 3NP through calpain
      inhibition. This suggests that, in certain models of neuronal death where zVAD
      showed protective effects, caspases but also calpains may be involved.

PMID- 15998527
TI  - Analgesic effects of the selective group II (mGlu2/3) metabotropic glutamate
      receptor agonists LY379268 and LY389795 in persistent and inflammatory pain
      models after acute and repeated dosing.
AB  - Group II (mGluR2/3) metabotropic glutamate receptors have been implicated in the
      mechanisms of persistent pain states. In the present study, the effects of the
      selective group II metabotropic glutamate receptor agonists LY379268 and LY389795
      were evaluated in the formalin test, carrageenan-induced thermal hyperalgesia and
      mechanical allodynia, and capsaicin-induced mechanical allodynia in rats. The
      agonists LY379268 and LY389795 produced dose-dependent decreases in formalin
      induced behaviors that were antagonized by the mGlu2/3 receptor antagonist
      LY341495. The group II antagonist LY341495 produced parallel shifts in the
      LY379268 dose-response curve, consistent with a competitive antagonism. LY379268
      decreased formalin-induced behaviors after intracisternal but not intrathecal
      administration, suggesting primarily a supraspinal site of action. Both LY379268
      and LY389795 produced a dose-related reversal of carrageenan-induced thermal
      hyperalgesia and capsaicin-induced mechanical allodynia, but had no effect on
      carrageenan-induced mechanical allodynia. Both agonists also increased response
      latencies in the hot plate test, but were without effect in the tail-flick test.
      However, both agonists produced motor impairment on the inverted screen at doses
      that were analgesic. Moreover, tolerance to the analgesic effects of LY379268
      developed after 4 days of once-daily repeated administration in the formalin,
      carrageenan, capsaicin and hot plate tests. The present findings indicate that
      group II (mGluR2/3) metabotropic glutamate receptors may be involved in the
      mechanisms of hyperalgesia and allodynia, however tolerance rapidly develops to
      these effects.

PMID- 15998528
TI  - How opening the cigarette market led to an increase in betel quid use in Taiwan.

PMID- 15998529
TI  - Center-surround inhibition deepens binocular rivalry suppression.
AB  - When dissimilar stimuli are presented to each eye, perception alternates between
      both images--a phenomenon known as binocular rivalry. It has been shown that
      stimuli presented in proximity of rival targets modulate the time each target is
      perceptually dominant. For example, presenting motion to the region surrounding
      the rival targets decreases the predominance of the same-direction target. Here,
      using a stationary concentric grating rivaling with a drifting grating, we show
      that a drifting surround grating also increases the depth of binocular rivalry
      suppression, as measured by sensitivity to a speed discrimination probe on the
      rival grating. This was especially so when the surround moved in the same
      direction as the grating, and was slightly weaker for opposed directions.
      Suppression in both cases was deeper than a no-surround control condition. We
      hypothesize that surround suppression often observed in area MT (V5)-a visual
      area implicated in visual motion perception-is responsible for this increase in
      suppression. In support of this hypothesis, monocular and binocular surrounds
      were both effective in increasing suppression depth, as were surrounds
      contralateral to the probed eye. Static and orthogonal motion surrounds failed to
      add to the depth of rivalry suppression. These results implicate a higher-level,
      fully binocular area whose surround inhibition provides an additional source of
      suppression which sums with rivalry suppression to effectively deepen suppression
      of an unseen rival target.

PMID- 15998530
TI  - Quantitative determination of sterols and other alcohols in overland flow from
      grazing land and possible source materials.
AB  - Organic marker compounds (biomarkers) can be used to identify the sources of
      waterborne pollutants. This paper examines sterols and other alcohols in overland
      flow from pasture-based grazing systems, possible agricultural source materials
      and water extracts of these source materials as a preliminary step to developing
      chemical profiles that can be used for tracing pollutants. The biomarkers were
      quantified using gas chromatography and gas chromatography-mass spectrometry
      techniques. Analyses of plant material show that some pasture species contain
      unique compounds, enabling their identification. For example, Arctotheca
      calendula (capeweed) contains an as yet unidentified compound (Arctotheca m/z
      163). Other pasture species that do not contain unique compounds do contain
      unique ratios of phytol, hexacosanol, octacosanol and 24-ethylcholesterol,
      enabling their identification. Analyses of faecal samples show that the ratios of
      sterols to stanols enable faeces to be distinguished from the pasture species,
      e.g. the ratio of 24-ethylcholesterol to 24-ethylcoprostanol was <1, generally
      <0.25 for faeces, while for most pasture species this ratio was >4. Using this
      ratio, qualitative apportioning of the sources of pollutants in overland flow to
      vegetation or faeces could be performed, but only in extreme cases (i.e. when the
      ratio <1 or >4). Decaying organic matter and surface soil appear to contain a
      composite of plant and faecal sterols. Sterols, being sparingly soluble in water
      and surface active, were not expected to be present in overland flow samples.
      Surprisingly, cholesterol and 24-ethylcoprostanol were found in both the
      particulate and filtrate fractions of most overland flow and water extracts of
      most source materials. Using the ratios of sterols to stanols, particulate
      organic material in water could be traced back to its broader source, i.e.
      vegetation or faeces.

PMID- 15998531
TI  - Phenol biodegradation and its effect on the nitrification process.
AB  - Phenol biodegradation under aerobic conditions and its effect on the
      nitrification process were studied, first in batch assays and then in an
      activated sludge reactor. In batch assays, phenol was completely biodegraded at
      concentrations ranging from 100 to 2500 mg l(-1). Phenol was inhibitory to the
      nitrification process, showing more inhibition at higher initial phenol
      concentrations. At initial phenol concentrations above 1000 mg l(-1), the level
      of nitrification decreased. In the activated sludge reactor, the applied ammonium
      loading rate was maintained at 140 mg N-NH(4)(+)l(-1)d(-1) (350 mg N-NH(4)(+)l(
      1)) during the operation time. However, the applied organic loading rate was
      increased stepwise from 30 to 2700 mg COD l(-1)d(-1) by increasing the phenol
      concentration from 35 up to 2800 mg l(-1). High phenol removal efficiencies,
      above 99.9%, were maintained at all the applied organic loading rates. Ammonium
      removal was also very high during the operation period, around 99.8%, indicating
      that there was no inhibition of nitrification by phenol.

PMID- 15998532
TI  - Screening analysis of river seston downstream of an effluent discharge point
      using near-infrared reflectance spectrometry and wavelet-based spectral region
      selection.
AB  - A methodology for screening analysis of river seston downstream of an industry
      effluent by using near-infrared reflectance spectrometry was developed. A wavelet
      transform (WT)-based strategy is used to select a spectral region in which the
      effect of the effluent on the optical properties of the seston is more evident.
      The methodology was applied to samples from the River Mumbaba in northeast
      Brazil. Four sites were monitored: two upstream (1 and 2), one at the discharge
      point of the effluent (3), and another downstream (4). Soft Independent Modelling
      of Class Analogies (SIMCA) models were built for site 1 and were then applied to
      the classification of samples from sites 2 and 4. The results reveal that the WT
      based spectral region selection is essential to ensure good sensitivity and
      specificity with respect to the detection of events associated to the effluent
      discharges at site 3. In fact, the changes in site 4 caused by the effluent are
      masked by other environmental factors when the full spectrum is employed.

PMID- 15998533
TI  - Effects of limb mass distribution on the ontogeny of quadrupedalism in infant
      baboons (Papio cynocephalus) and implications for the evolution of primate
      quadrupedalism.
AB  - Primate quadrupedal kinematics differ from those of other mammals. Several
      researchers have suggested that primate kinematics are adaptive for safe travel
      in an arboreal, small-branch niche. This study tests a compatible hypothesis that
      primate kinematics are related to their limb mass distribution patterns. Primates
      have more distally concentrated limb mass than most other mammals due to their
      grasping hands and feet. Experimental studies have shown that increasing distal
      limb mass by adding weights to the limbs of humans and dogs influences
      kinematics. Adding weights to distal limb elements increases the natural period
      of a limb's oscillation, leading to relatively long swing and stride durations.
      It is therefore possible that primates' distal limb mass is responsible for some
      of their unique kinematics. This hypothesis was tested using a longitudinal
      ontogenetic sample of infant baboons (Papio cynocephalus). Because limb mass
      distribution changes with age in infant primates, this project examined how these
      changes influence locomotor kinematics within individuals. The baboons in this
      sample showed a shift in their kinematics as their limb mass distributions
      changed during ontogeny. When their limb mass was most distally concentrated (at
      young ages), stride frequencies were relatively low, stride lengths were
      relatively long, and stance durations were relatively long compared to older ages
      when limb mass was more proximally concentrated. These results suggest that the
      evolution of primate quadrupedal kinematics was tied to the evolution of grasping
      hands and feet.

PMID- 15998534
TI  - Emergent properties of electrically coupled smooth muscle cells.
AB  - Asynchronous and synchronous calcium oscillations occur in a variety of cells. A
      well-established pathway for intercellular communication is provided by gap
      junctions which connect adjacent cells and can mediate electrical and chemical
      coupling. Several experimental studies report that cells presenting only a
      transient increase when freshly dispersed may oscillate when they are coupled.
      Such observations suggest that the role of gap junctions is not only to
      coordinate calcium oscillations of adjacent cells. Gap junctions may also be
      important to generate oscillations. Here we illustrate the emergent properties of
      electrically coupled smooth muscle cells using a model that we recently proposed.
      A bifurcation analysis in the case of two cells reveals that synchronous and
      asynchronous calcium oscillations can be induced by electrical coupling. In a
      larger population of smooth muscle cells, electrical coupling may result in the
      creation of groups of cells presenting synchronous calcium oscillations. The
      elements of one group may be distant from each other. Moreover, our results
      highlight a general mechanism by which gap junctional electrical coupling can
      give rise to out of phase calcium oscillations in smooth muscle cells that are
      non-oscillating when uncoupled. All these observations remain true in the case of
      non-identical cells, except that the solution corresponding to synchronous
      calcium oscillations disappears and that the formation of groups is sensitive to
      the degree of heterogeneity.

PMID- 15998535
TI  - Analysis of potential lubricants for in vitro wear testing.
AB  - OBJECTIVES: A critical testing aspect for a reliable two-body wear simulation may
      be the lubricity condition. The main hypothesis tested in this study was that,
      over the experiment duration, the presence or absence of lubricants would provide
      to a composite similar wear rates to those observed under human saliva
      lubrication. METHODS: Seventy specimens, fabricated from a minifill composite,
      were tested in a programmable logic controlled wear simulator with human saliva
      (HS), mucin-based artificial saliva (MC), carboxymethylcellulose-containing
      saliva (CM), deionized water (DW) or with no lubrication (UN). Wear depth was
      quantified at the end of 1000, 5000, 10,000 and 50,000 cycles and at each 50,000
      through 250,000 cycles. RESULTS: Over all the test period, UN led to the greatest
      wear. Initially, lubrication resulted in no significant differences among the
      wear rates. Subsequently, up to 50,000 cycles, depths of wear provided by HS and
      MC were still similar, being the lowest, whereas DW yielded greater wear than CM.
      Later, interposition of CM and HS resulted in equivalent wear. At 250,000 cycles,
      wear of the composite ranked as follows: MC<HS<CM<DW<UN. Regression analyses
      showed that for all lubricity conditions wear of the composite rose
      logarithmically with number of cycles. SIGNIFICANCE: The role of the interposed
      lubricant was of importance for the wear testing. The present findings supported
      by studies on the lubricity ability of mucin-based artificial saliva, allowed to
      conclude that this preparation may be considered as a potential lubricant for in
      vitro wear test purposes.

PMID- 15998536
TI  - Brief report: young people at risk for eating disorders in Southeast Brazil.
AB  - A representative sample of 7-14-year-old young people in southeast Brazil
      (N=1251) was assessed using standardized parent and youth interviews, thereby
      identifying an 'at-risk' group of young people who met one or more DSM-IV
      criteria for anorexia and/or bulimia nervosa. These young people were compared
      with an age and gender matched comparison group for body mass index (BMI) and
      socio-economic status (SES). The prevalence of young people at risk for eating
      disorders was 1.4% (higher in females and rising with age). 'At-risk' individuals
      did not differ from controls in BMI but were of higher SES. In Brazil, the link
      between symptoms of eating disorders and higher SES is not just a referral
      artefact but is evident in a representative community sample. This might reflect
      a stronger preference for thinness among more westernized social groups.

PMID- 15998537
TI  - Towards a model of suicidal ideation for Hong Kong Chinese adolescents.
AB  - This study tested a model of suicidal ideation with family cohesion,
      expressiveness, conflicts, teacher support, teacher-student relationships and
      peer support as antecedents, and self-esteem and depression as mediators. Data
      was collected from survey questionnaires with 433 Hong Kong Chinese adolescents.
      The results showed that only family cohesion, conflicts, teacher support and peer
      support significantly predicted self-esteem and depression, with depression being
      a strong mediator of suicidal ideation. Implications of the findings for future
      research were discussed.

PMID- 15998538
TI  - Biological performances of collagen-based scaffolds for vascular tissue
      engineering.
AB  - Collagen is widely used for biomedical applications and it could represent a
      valid alternative scaffold material for vascular tissue engineering. In this
      work, reconstituted collagen films were prepared from neutralized acid-soluble
      solutions for subsequent haemocompatibility and cell viability performance
      assays. First, haemoglobin-free, thrombelastography and platelet adhesion tests
      were performed in order to investigate the blood contact performance. Secondly,
      specimens were seeded with endothelial cells and smooth muscle cells, and cell
      viability tests were carried out by MTT and SEM. Results show that neutralized
      acid-soluble type I collagen films do not enhance blood coagulation, do not alter
      normal viscoelastic properties of blood and slightly activate platelet adhesion
      and aggregation. Cell culture shows that the samples are adequate substrates to
      support the adhesion and proliferation of endothelial and smooth muscle cells.

PMID- 15998539
TI  - Enhanced vascular-related cellular affinity on surface modified copolyesters of 3
      hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx).
AB  - Random copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate, short as PHBHHx,
      was surface modified by ammonia plasma treatment and/or fibronectin coating,
      respectively. The improved results were demonstrated by better growth of human
      umbilical vein endothelial cells (HUVECs) and rabbit aorta smooth muscle cells
      (SMCs) on the surface of ammonia plasma-treated PHBHHx coated with fibronectin
      (PFn-PHBHHx), compared with the fibronectin-coated (Fn-PHBHHx) or uncoated
      PHBHHx, respectively, although XPS analysis and ELISA demonstrated higher
      fibronectin adsorption on Fn-PHBHHx than on PFn-PHBHHx. Confocal microscopy
      observation showed that the specific co-localization of fibronectin with F-actin
      was impaired on PFn-PHBHHx, while it was almost lost on Fn-PHBHHx compared with
      pristine PHBHHx or plasma-treated PHBHHx (P-PHBHHx). These were attributed to the
      generation of new nitrogen- and oxygen-containing groups on the PHBHHx surface by
      the ammonia plasma treatment, which led to increased polar components that
      enhanced polymer surface energy and hydrophilic properties on P-PHBHHx. The most
      prominent effect of PFn-PHBHHx was its stimulation of HUVECs proliferation.
      HUVECs on PFn-PHBHHx formed a confluent monolayer after 3 days of incubation,
      while SMCs were unable to form a sub-confluent layer. The above evidences
      revealed that PFn-PHBHHx would benefit endotheliazation rather than SMCs
      proliferation. We therefore believed that PFn-PHBHHx would be a promising
      material as a luminal surface of vascular grafts.

PMID- 15998540
TI  - Dimethyl sulfoxide potentiates death receptor-mediated apoptosis in the human
      myeloid leukemia U937 cell line through enhancement of mitochondrial membrane
      depolarization.
AB  - Dimethyl sulfoxide (DMSO) is a widely used prototypical chemical inducer of cell
      differentiation. In the present study, the effects of DMSO on susceptibility of
      human myeloid leukemia U937 cells towards ligation of distinct death receptors
      (DRs) were investigated. DMSO sensitized cells towards induction of apoptosis by
      anti-Fas antibody, tumour necrosis factor-alpha or Apo2 ligand/TNF-related
      apoptosis-inducing ligand (TRAIL). Apart from increasing Fas levels, DMSO did not
      affect expression of proteins in death signal transduction, such as Bcl-2 family
      proteins, FADD, caspase-3 and -8, the inhibitor of apoptosis proteins (IAPs) or
      cFLIP(L). However, DMSO significantly potentiated mitochondrial membrane
      depolarization, suggesting that this mechanism might be involved in sensitisation
      of myeloid cells to DR-mediated apoptosis.

PMID- 15998541
TI  - Molecular characterization of a novel pattern recognition protein from
      nonspecific cytotoxic cells: sequence analysis, phylogenetic comparisons and anti
      microbial activity of a recombinant homologue.
AB  - Nonspecific cytotoxic cells (NCC) are the first identified and most extensively
      studied killer cell population in teleosts. NCC kill a wide variety of target
      cells including tumor cells, virally transformed cells and protozoan parasites.
      The present study identified a novel evolutionarily conserved
      oligodeoxynucleotide (ODN) binding membrane protein expressed by channel catfish
      (Ictalurus punctatus) NCC. Peptide fingerprinting analysis of the ODN binding
      protein (referred to as NCC cationic anti-microbial protein-1/ncamp-1) identified
      a peptide that was used to design degenerate primers. A catfish NCC cDNA library
      was used as template with these primers and the PCR-amplified product was
      sequenced. The translated sequence contained 203 amino acids (molecular mass of
      22,064.63 Da) with characteristic lysine rich regions and a pI=pH 10.75. Sequence
      comparisons of this protein indicated similarity to zebrafish (51.2%) histone
      family member 1-X and (to a lesser extent) to trout H1. A search of EST databases
      confirmed that ncamp-1 is also expressed in various tissues of channel catfish as
      well as zebrafish. Inspection for signature repeats in ncamp-1 and comparisons
      with histone-like peptides from different species indicated the presence of
      multiple lysine based motifs composed of AKKA or PKK repeats. The novel protein
      was cloned, expressed in E. coli and the recombinant was used to generate rabbit
      anti-serum. The recombinant ncamp-1 bound GpC and CpG ODNs and was detected with
      homologous anti-ncamp-1 polyclonal antibodies. Western blots of NCC membranes
      using anti-ncamp-1 serum detected a 29 kDa protein. Binding competition
      experiments demonstrated that anti-ncamp-1 antibodies and GpC bound to the same
      protein on NCC. Two different truncated forms of ncamp-1 as well as the full
      length recombinant protein exhibited anti-microbial activity. The present study
      demonstrated the expression by NCC of a new membrane protein that may participate
      in the recognition of bacterial DNA and as such participate in innate anti
      microbial immune responses in teleosts.

PMID- 15998542
TI  - Age-dependent (+)MDMA-mediated neurotoxicity in mice.
AB  - In the present study the effects of a neurotoxic regimen of (+)-MDMA (20 mg/kgx4,
      s.c.) in 4- and 10-week-old C57Bl/6J mice during treatment and 7 days post
      treatment were examined. Rectal temperatures monitored between (+)-MDMA
      injections (30 min post-injection/2 h intervals) revealed hyperthermic responses
      in both age groups, with the magnitude of the response significantly greater in
      older mice. Seven days post-treatment, immunoblot analyses of the vesicular
      monoamine transporter 2 (VMAT2), and tyrosine hydroxylase (TH) revealed
      significant reductions (-37 and -58%, respectively) in the older animals, but not
      in the younger group, compared to age-matched controls. Dopamine transporter
      (DAT) expression was significantly reduced in both 4- and 10-week-old animals (26
      and 69.7%, respectively). (+)-MDMA-treated animals also exhibited significantly
      lower levels of striatal dopamine, and 3,4-dihydroxyphenylacetic acid than
      controls, again the effect being more pronounced in the older animals. Although
      both age groups showed evidence of (+)-MDMA-induced toxicity, our data revealed
      that older animals exhibited a greater hyperthermic response to (+)-MDMA and were
      also are more susceptible to subsequent dopaminergic damage than the younger
      animals.

PMID- 15998543
TI  - Toll-like receptor, MHC II, B7 and cytokine expression by porcine monocytes and
      monocyte-derived dendritic cells in response to microbial pathogen-associated
      molecular patterns.
AB  - To evaluate effects of treatment with pathogen-associated molecular patterns
      (PAMPs) on toll-like receptor (TLR), MHC II, B7 and cytokine expression, pig
      monocytes and monocyte-derived DCs (moDCs) were treated with LPS, CpG,
      lipoteichoic acid (LTA), poly IC or peptidoglycan (Pep). Monocytes and moDCs
      treated with LPS, CpG, LTA, poly IC or Pep altered expression of at least one TLR
      (4, 5 and 9) and up-regulated MHC II and/or B7. The mRNA for IL-4 was not
      detected after any treatment. Treatment with LPS or LTA tended to up-regulate
      mRNA for TLR 4, Th-1 (IFN-gamma and IL-12p35) and Th-2 cytokines (IL-10 and IL
      13). Poly IC or CpG tended to up-regulate TLR 9 and Th-1 cytokines. Porcine
      monocytes and moDCs like those of humans and mice responded to microbial PAMPs by
      altering TLR expression, up-regulating MHC II and B7 and altering cytokine
      expression toward Th-1 and/or Th-2, which may steer immune response. Hence,
      porcine moDCs and monocytes are likely able to discriminate between
      microorganisms using TLRs which determine cytokine expression and immune response
      bias.

PMID- 15998544
TI  - Beta2-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12
      production in monocytes.
AB  - We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on
      monocyte-derived cytokines, interleukin (IL)-18 and IL-12 production in
      lipopolysaccharide (LPS)-stimulated monocytes derived from human peripheral blood
      mononuclear cells (PBMCs), as in vitro model of sepsis. The study found that
      beta2-AR agonists inhibited IL-18 and IL-12 production in monocytes, and that AR
      agonist activity was antagonized by the selective beta2-AR antagonist,
      butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a
      similar inhibitory pattern of IL-18 and IL-12 production. IL-12 production
      induced by LPS was inhibited by anti-IL-18 Ab, but IL-18 production by LPS was
      not inhibited by anti-IL-12 Ab, showing that LPS induced IL-18 production without
      IL-12 production. Therefore, the stimulation of beta2-AR might be beneficial in
      the treatment of sepsis through inhibiting LPS-elicited IL-18.

PMID- 15998545
TI  - A real-time PCR assay for measuring alcelaphine herpesvirus-1 DNA.
AB  - Alcelaphine herpesvirus-1 (AlHV-1) is a rhadinovirus that causes malignant
      catarrhal fever in certain ruminant species and is an important pathogen in
      Africa and other areas where carrier species and clinically susceptible ruminants
      intermingle. In this study, a real-time PCR for AlHV-1 DNA was developed and
      compared to an established nested PCR. The nested PCR amplifies a region of the
      AlHV-1 gene coding for a transactivator protein (ORF 50), while the real-time PCR
      assay targets the AlHV-1 gene coding for a tegument protein (ORF 3). The real
      time PCR assay reproducibly detected 10 copies of target DNA. In a dilution
      series of the target DNA there was linearity of the assay across 8 orders of
      magnitude (10(1)-10(9) copies). The nested PCR was more sensitive (approximately
      with 1 log) than the real-time PCR. The assay specifically amplified samples
      containing only AlHV-1, but not other common herpesviruses of cattle. In
      conclusion, we have developed a rapid, relatively sensitive, and reliable real
      time PCR assay specific for AlHV-1. Similar to the real-time PCR for Ovine
      herpesvirus-2, this assay should prove useful for differential diagnostics of
      clinical MCF and for research to better define the epidemiology of AlHV-1 in
      wildebeest as well as in animals with wildebeest-associated MCF.

PMID- 15998546
TI  - Effects of copper on the fertilization success of the soft coral Lobophytum
      compactum.
AB  - This study provides the first information on the effects of various
      concentrations of copper on the fertilization success of gametes from the soft
      coral Lobophytum compactum. Two experiments were conducted to determine the
      effect of copper on fertilization success during the mass coral spawning in 2004
      on the Great Barrier Reef (GBR). The results from the first experiment showed a
      surprising resistance to copper with control treatments showing 90% fertilization
      compared to 65% fertilization in measured copper concentrations up to 132
      microg/L. Copper concentrations of 69 microg/L and higher resulted in
      significantly reduced fertilization success when compared to the controls. Copper
      doses were increased in experiment 2 and the EC50 value for copper effects on
      fertilization success was 261 microg/L (208-328 microg/L, 95% confidence limits).
      In this follow-up experiment, fertilization success was significantly lower than
      the controls after exposure to copper concentrations of 117 microg/L and above.
      The EC50 value reported here is much higher than those found in the literature on
      fertilization experiments conducted on hard coral gametes and also for the
      fertilization success of other marine organisms, including sea urchins, oysters
      and fish.

PMID- 15998547
TI  - Decubitus direct current treatment (DDCT) of pressure ulcers: results of a
      randomized double-blinded placebo controlled study.
AB  - Electrostimulation for the treatment of pressure sores remains problematic and
      controversial. We studied the decubitus direct current treatment (DDCT)
      electrostimulation treatment of pressure sores stage 3 degree, with respect to
      rates of ulcer closure and wound area reduction. This was a multicenter, double
      blind, randomized, placebo-controlled study involving 11 departments of geriatric
      and rehabilitation medicine including 63 patients. We compared a placebo treated
      group (PG) with an active treatment group (TG). Treatment lasted for 8
      consecutive weeks, followed by a 12-week-period of follow-up. At day 57 (end of
      treatment) and at day 147 (end of follow-up), there was no difference between the
      groups with regards to rates of complete closure of ulcers (p=0.28 and 0.39,
      respectively), as well as for the mean time needed to achieve complete wound
      closure (p=0.16). Absolute ulcer area reduction and speed rate of wound area
      reduction (reflected by change from baseline ulcer area, percentage) were better
      in participants allocated in the treatment group only until day 45 (standardized
      estimate for trend of healing speed -0.44 and -0.14 for TG and PG, respectively).
      Afterwards, there were no differences between the two groups. A logistic
      regression analysis favored complete healing in TG, compared with PG (odds ratio
      1.6, CI 0.4-4.73). Analysis of per protocol patients revealed that time needed
      for wound closure was 52% longer in PG (p=0.03, compared with TG). The results
      suggest that DDCT treatment for pressure ulcers grade 3 degree, in addition to
      the conservative wound care, may be useful in accelerating the healing process
      during the first period of care.

PMID- 15998548
TI  - Family coverage expansions: impact on insurance coverage and health care
      utilization of parents.
AB  - With the passage of the Personal Responsibility and Work Opportunity
      Reconciliation Act of 1996 (PRWORA), Medicaid eligibility ceased to be tied to
      receipt of cash assistance. Since then, states have had a growing number of
      opportunities to expand health coverage to low-income working families beyond
      previous AFDC limits. As of 2001, 20 states have raised income eligibility limits
      for parents to or beyond 100% of the Federal Poverty Level. First, we use the
      Current Population Survey to study the effect of states' expansions on the
      insurance rates of adults and to estimate the crowd-out of private insurance. We
      find that eligible adults living in a state that expanded coverage are more
      likely to be insured. We find a take-up rate of 14.8%. Our results suggest that
      24% of this increase is due to a reduction in private coverage. Next, we use the
      Behavioral Risk Factor Surveillance System to examine changes in health care
      utilization. We find that these expansions increased cancer-screening rates. Of
      previously uninsured mothers not receiving cancer screening, 29% now receive
      these screens. Finally, our results indicate the expansions decreased the
      likelihood that a parent needed to see a doctor but did not because of cost.

PMID- 15998549
TI  - No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese
      population.
AB  - Autism is a child-onset pervasive developmental disorder, with a significant role
      of genetic factors in its development. Genome-wide linkage studies have suggested
      a 7q region as a susceptibility locus for autism. We investigated several single
      nucleotide polymorphisms (SNPs) of Forkhead Box P2 (FOXP2) and Protein-Tyrosine
      Phosphatase, Receptor-type, Zeta-1 (PTPRZ1) at the 7q region in Japanese patients
      with autism and healthy controls. No significant difference was observed, after
      correction for the multiple testing, in allele, genotype or haplotype frequencies
      of the SNPs of FOXP2 or PTPRZ1 between patients and controls. No evidence was
      thus obtained for a major role of FOXP2 or PTPRZ1 in the development of autism.

PMID- 15998550
TI  - Advanced multimodal visualisation of clinical gait and fluoroscopy analyses in
      the assessment of total knee replacement.
AB  - Traditional gait and fluoroscopy analysis of human movement are largely utilised
      but are still limited in registration, integration, synchronisation and
      visualisation capabilities. The present work exploits the features of a recently
      developed software tool based on multimodal display (Data Manager developed
      within the EU-funded project 'Multimod') in an exemplary clinical case. Standard
      lower limb gait analysis, comprising segment position, ground reaction force and
      EMG data collection, and three-dimensional fluoroscopy analysis at the replaced
      joint were performed in a total knee replacement patient while ascending stairs.
      Clinical information such as X-rays and standard scores were also available. Data
      Manager was able to import all this variety of data and to structure these in an
      original hierarchical tree. Bone and prosthesis component models were registered
      to corresponding marker position data for effective three-dimensional animations.
      These were also synchronised with corresponding standard video sequences.
      Animations, video, time-histories of collected and also processed data were shown
      in various combinations, according to specific interests of the bioengineering
      and medical professionals expected to observe and to interpret this large amount
      of data. This software tool demonstrated to be a valuable means to enhance
      representation and interpretation of measurements coming from human motion
      analysis. In a single software, a thorough and effective clinical and
      biomechanical analysis of human motion was performed.

PMID- 15998551
TI  - Management of recurrent malignant pleural effusions with a chronic indwelling
      pleural catheter.
AB  - Many patients with various forms of cancer develop sooner or later malignant
      pleural effusions, resulting in feelings of discomfort and reduced quality of
      life. Several palliative options exist, including repeated thoracocentesis and
      pleurodesis with a sclerosing agent. However, these "therapeutic" possibilities
      are not always successful and sometimes even contraindicated. Also, patients need
      to visit the hospital regularly or have to stay hospitalised for several days. A
      chronic indwelling pleural catheter could provide a simple, completely outpatient
      way to provide respiratory relief and improvement in quality of life in patients
      with malignant pleural effusions. We evaluated retrospectively the course of 17
      patients with malignant pleural effusions who were treated with a chronic
      indwelling pleural catheter (PleurX). Eligible patients were selected in the
      years 2001-2003 from a single institution. In 70-80% of patients, catheter use
      was uncomplicated and provided significant symptom relief. Mean duration of
      catheter use was 2.3 (range 1-6) months. Mean fluid removal was 360 (range 150
      1000 cc) per 24 h in the first weeks of treatment. Infection was seen in two
      (12%) patients, dislocation of the catheter in three (18%). In the final
      analysis, catheter use was unsatisfactory in two patients (12%). We conclude that
      a chronic indwelling catheter is a very useful tool in the management of
      recurrent malignant pleural effusions. Treatment can be accomplished completely
      at home, whereas complications are rare.

PMID- 15998552
TI  - Nutritional treatment of incipient thyroid autoimmune disease. Influence of
      selenium supplementation on thyroid function and morphology in children and young
      adults.

PMID- 15998553
TI  - Can home parenteral nutrition be provided by non-specialized centres?: The Dutch
      experience.

PMID- 15998554
TI  - Effect of adjuvant on reactogenicity and long-term immunogenicity of the malaria
      Vaccine ICC-1132 in macaques.
AB  - ICC-1132 is a malaria vaccine candidate based on a modified hepatitis B virus
      core particle (HBc) bearing putative protective epitopes from the
      circumsporozoite protein (CS) of Plasmodium falciparum. While the epitope carrier
      itself is immunogenic, its potency can be increased by formulation with
      adjuvants. As a prelude to Phase I clinical trials, rhesus macaques were
      immunised twice with GMP grade ICC--1132 in saline or formulated with the
      adjuvants Alhydrogel (Alhydrogel) or Montanide((R)) ISA 720 (Montanide). Both
      adjuvant formulations gave significant humoral responses after the first
      injection, with titres increasing further after the second dose. The Montanide
      formulation was the most immunogenic, but undesirable reactogenicity in the form
      of sterile abscesses was associated with higher dosage levels of ICC--1132. These
      side effects could be avoided with lower antigen load, or by formulation of the
      second dose in Alhydrogel. Such measures also reduced peak titres and longevity
      of antibodies against CS, demonstrating the delicate balance between
      immunogenicity and reactogenicity of new vaccine formulations.

PMID- 15998555
TI  - A subunit vaccine against hemorrhagic enteritis adenovirus.
AB  - Hemorrhagic enteritis virus (HEV) is an adenovirus that infects turkeys and
      causes immunosuppression and mortality. The virus used for the inactivated
      vaccine is extracted from spleens of infected turkeys, since its propagation in
      tissue cultures or embryonated eggs is unsuitable for mass production. The aim of
      this study was to develop a subunit vaccine based on a capsid protein of the
      virus. The knob protein, together with an adjacent part of the shaft domain
      pertaining to the fiber protein of HEV, was expressed in Escherichia coli and
      tested as a vaccine. Vaccination with this recombinant protein conferred
      protection against challenge in controlled and in floor-pen experiments. This
      finding suggests that the knob protein may be used as safe and efficient vaccine
      against hemorrhagic enteritis of turkeys. The possibility that the knob proteins
      of other adenoviruses may be protective and serve as vaccine is also discussed.

PMID- 15998556
TI  - (90)Sr, (210)Po and (210)Pb in lichen and reindeer in Norway.
AB  - Concentrations of (90)Sr, (210)Po and (210)Pb in lichen and reindeer were studied
      in central (Ostre Namdal) and southern Norway (Vaga) during 2000-2003. The study
      focussed on potential differences in concentrations of these nuclides in reindeer
      of different ages. Concentrations of (90)Sr in bones of approximately 10 year old
      adult females were about 40% higher than those in calves' antlers ((90)Sr
      concentrations in antlers and bones of calves are similar), while the available
      data from Vaga suggest that (90)Sr concentrations in reindeer calves decreased
      with an effective ecological half-time of 9.03+/-0.06 years during 1988-2002.
      Furthermore, (90)Sr concentrations were 50-80% higher in bone of reindeer of a
      similar age from Vaga compared to those from Ostre Namdal. Concentrations of
      (210)Po and (210)Pb in muscle and liver tissues were comparable to those reported
      for reindeer in other Nordic areas, with no significant difference in (210)Po and
      (210)Pb concentrations between adults and calves or between reindeer from the two
      different study areas.

PMID- 15998557
TI  - Re: Renton T, Hankins M, Sproate C, McGurk M. A randomised controlled clinical
      trial to compare the incidence of injury to the inferior alveolar nerve as a
      result of coronectomy and removal of mandibular third molars. Br J Oral
      Maxillofac Surg 2005;43(4):7-12.

PMID- 15998558
TI  - Penetrating grease gun injury in the face.
AB  - We present the case of a sailor who sustained a penetrating grease gun injury to
      his face, and the challenging subsequent series of events.

PMID- 15998559
TI  - Island biogeography and landscape structure: integrating ecological concepts in a
      landscape perspective of anthropogenic impacts in temporary wetlands.
AB  - Although our understanding of environmental risk assessment in temporary wetlands
      has been improved by the use of multi-species toxicity testing, we still know
      little of how landscape variables mediate the strength of, and recovery from,
      anthropogenic stress in such ecosystems. To bridge this research gap, we provide
      a theoretical framework of the response of temporary wetlands to anthropogenic
      disturbance along a habitat-isolation continuum based on island biogeography
      theory, landscape ecology and dispersal and colonization strategies of temporary
      wetland organisms.

PMID- 15998560
TI  - Scale and causes of lead contamination in Chinese tea.
AB  - We investigated the scale and causes of Pb contamination in Chinese tea. Lead
      concentrations in 1,225 tea samples collected nationally between 1999 and 2001
      varied from <0.2 to 97.9 mg kg(-1) dry weight (DW), with 32% of the samples
      exceeding the national maximum permissible concentration (MPC) of 2.0 mg kg(-1)
      DW and a significant difference between tea types. There was an increasing trend
      in tea Pb concentration from 1989 to 2000. Proximity to highway and surface dust
      contamination were found to cause elevated Pb concentrations in tea leaves.
      Furthermore, Pb concentration in tea leaves correlated significantly and
      positively with soil extractable Pb, and negatively with soil pH, suggesting that
      root uptake of Pb from soils also contributed to Pb accumulation in tea.
      Potential contributions to human Pb intake from drinking tea were small at the
      median or national MPC Pb values, but considerable at the highest concentration
      found in the study.

PMID- 15998561
TI  - Colonisation of a Zn, Cd and Pb hyperaccumulator Thlaspi praecox Wulfen with
      indigenous arbuscular mycorrhizal fungal mixture induces changes in heavy metal
      and nutrient uptake.
AB  - Plants of the Zn, Cd and Pb hyperaccumulator Thlaspi praecox Wulfen
      (Brassicaceae) inoculated or not with indigenous arbuscular mycorrhizal (AM)
      fungal mixture were grown in a highly Cd, Zn and Pb contaminated substrate in
      order to evaluate the functionality of symbiosis and assess the possible impact
      of AM colonisation on heavy metal uptake and tolerance. The results suggest AM
      development in the metal hyperaccumulating T. praecox is favoured at elevated
      nutrient demands, e.g. during the reproductive period. AM colonisation parameters
      positively correlated with total soil Cd and Pb. Colonised plants showed
      significantly improved nutrient and a decreased Cd and Zn uptake as revealed by
      TRXRF, thus confirming the functionality of the symbiosis. Reduced heavy metal
      uptake, especially at higher soil metal contents, indicates a changed metal
      tolerance strategy in colonised T. praecox plants. This is to our knowledge the
      first report on AM colonisation of the Zn, Cd and Pb hyperaccumulator T. praecox
      in a greenhouse experiment.

PMID- 15998562
TI  - Effect of soil characteristics on Cd uptake by the hyperaccumulator Thlaspi
      caerulescens.
AB  - The influence of soil characteristics on the phytoremediation potential of
      Thlaspi caerulescens is not well understood. We investigated the effect of soil
      pH and Cd concentration on plant Cd uptake on one soil type, and the variation in
      Cd uptake using a range of field contaminated soils. On soils with total Cd
      concentrations of 0.6-3.7 mg kg(-1), T. caerulescens (the Ganges ecotype)
      produced greater biomass in the pH range 5.1-7.6 than at pH 4.4. The highest
      plant Cd concentration (236 mg kg(-1)) and Cd uptake (228 microg pot(-1)) were
      observed at pH 5.1. On soils with total Cd concentrations of 2.6-314.8 mg kg(-1),
      shoot Cd concentrations were 10.9-1,196 mg kg(-1). Multiple regression analysis
      indicated that higher Cd in soil, low pH (within the range of >5) and coarser
      texture were associated with higher Cd concentration and Cd uptake by T.
      caerulescens.

PMID- 15998563
TI  - Is erectile dysfunction an indicator for increased risk of coronary heart disease
      and stroke?
AB  - BACKGROUND: Considered to be a manifestation of a generalized vascular disease,
      erectile dysfunction (ED) could serve as an indicator for future cardiovascular
      events. Aim of this study was therefore to evaluate the role of ED as a predictor
      for coronary heart disease (CHD) and stroke. METHODS: Men participating in a
      health-screening project in the area of Vienna completed the International Index
      of Erectile Function-5 questionnaire (IIEF5) to assess prevalence and severity of
      ED. Additionally, all men underwent a detailed health examination. The risk for
      CHD or stroke within 10 years depending on the severity of ED was estimated
      according to Framingham risk profile algorithms. RESULTS: In the CHD risk cohort
      (n = 2.495; 46.2 +/- 9.9 yrs) men with moderate/severe ED (IIEF5 5-16; n = 163)
      had a 65% increased relative risk for developing CHD within 10 yrs compared to
      those without ED (IIEF5 22-25; n = 1.784) (absolute risk: 8.0% for no ED to 13.2%
      for moderate/severe ED; p < 0.001). Relative risk increase ranged from 13.9% for
      those aged 30-39 yrs (p = 0.121), to 42.2% for 40-49 yrs (p = 0.012), 27.7% for
      50-59 yrs (p = 0.048) and 27.1% for 60-69 yrs (p = 0.021). In the stroke risk
      population (n = 644; 61.3 +/- 5.1 yrs) men with moderate/severe ED (n = 99) were
      at a 43% relative risk increase for a stroke within 10 years (absolute risk: 9.3%
      for no ED to 13.3% for moderate/severe ED; p = 0.041). Increased risk varied
      between 38.6% for men aged 55-59 yrs (p = 0.013), 24.7% for 60-64 yrs (p =
      0.072), 35.9% for 65-69 yrs (p = 0.046) and 43.6% for 70-74 yrs (p = 0.049).
      CONCLUSIONS: Moderate to severe ED, but not mild ED is associated with a
      considerably increased risk for CHD or stroke within 10 years. A thorough medical
      surveillance seems therefore advisable for men with ED including cardiological
      evaluation, treatment of risk factors and lifestyle modifications.

PMID- 15998564
TI  - Effectiveness of oral desmopressin therapy in posterior urethral valve patients
      with polyuria and detection of factors affecting the therapy.
AB  - OBJECTIVES: The present study aims to evaluate the effect of desmopressin
      treatment on urine output, density and glomerular filtration rate (GFR) in
      patients with posterior urethral valve (PUV) and the factors affecting the
      response to this treatment. METHODS: A total of 68 PUV patients who were followed
      up after valve ablation were examined with the fluid intake, urine output and
      GFR. Sixteen patients who were polyuric (a urine output more than 30 ml/kg/day)
      and had hypoosmolar urine (urinary density of 1015 or lower) included in the
      study. Blood chemistry and serum ADH level were studied. Following 5 days of
      observation, patients were given DDAVP perorally with a dosage of 0.4 mg/day, two
      equal doses per day. After 7 days and after a 3 month period of treatment,
      voiding characteristics, day-time and night-time urine densities and also GFR
      have been re-evaluated. RESULTS: The mean age was 6.8 years (range 2 to 11
      years). The mean age at valve ablation was 20.7 months (range 5 months to 6
      years). The mean daily urine output during first week and at the third month of
      the treatment had decreased significantly (p=0.004 and p=0.006). There was
      increase in night-time and day-time urine density in 10 patients (62%) and in 13
      patients (81%) respectively at the third month evaluation. Increments in urine
      density were statistically significant for the third month evaluation. Nine (56%)
      patients had ADH levels within normal (<7 pcg/ml) levels and 7 patients had
      higher levels. There was no statistically significant difference between
      pretreatment and posttreatment micturation characteristics. However patients with
      voiding dysfunction responded better to DDAVP treatment. CONCLUSIONS:
      Desmopressin treatment improves polyuria in PUV patients. The responses are
      better particularly in PUV patients with significant bladder dysfunction. This
      supports the harmful role of polyuria on bladder dysfunction. The DDAVP treatment
      improves the day-time and night-time in PUV patients. Combination of DDAVP
      treatment with overnight catheterization may be a good alternative that needs to
      be evaluated by further prospective randomized studies.

PMID- 15998565
TI  - Coenzyme specificity in fungal 17beta-hydroxysteroid dehydrogenase.
AB  - The 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus is
      an NADP(H)-dependent member of the short-chain dehydrogenase/reductase
      superfamily (SDR) that belongs to the cP1 classical subfamily. Here, we have
      created several mutants by site-directed mutagenesis, and through these we have
      studied the amino acid residues that are responsible for coenzyme binding and
      specificity. The Thr202Val and Thr202Ile mutants were inactive, thus confirming
      the importance of Thr202 for the appropriate orientation of the coenzyme that
      enables the hydride transfer. The Ala50Arg and Asn51Arg mutants had increased
      rates of NADPH dissociation, and thus an enhanced substrate oxidation with NADP+,
      while the Asn51Arg mutant also showed an increased rate of NADP+ dissociation,
      and thus an enhanced substrate reduction with NADPH. Addition of a negatively
      charged amino acid residue at the first position after the second beta-strand
      (Tyr49Asp) affected the coenzyme specificity and turned the enzyme into an NAD+
      dependent oxidase resembling the cD1d subfamily members.

PMID- 15998566
TI  - Somatosensory-evoked potentials are influenced differently by isometric muscle
      contraction of stimulated and non-stimulated hand in humans.
AB  - Chronic pain is associated with motor dysfunctions, and stimulation of the motor
      cortex has been shown to alleviate chronic pain. Recently Nakata et al. [Pain 107
      (2004) 91-98] showed differentiated patterns of neuromagnetic evoked fields
      following painful laser stimulation during phasic movements of stimulated and non
      stimulated hand. Phasic movements and static contractions differ in their
      functional activation of the motor cortices. Therefore, we decided to analyze the
      effects of isometric contractions of intrinsic right and left hand muscles on
      cortical sources of somatic-evoked potentials related to a painful galvanic
      stimulation of the right middle finger. Using spatio-temporal source dipole
      analysis of 111 electroencephalographic signals in 10 right-handed men, source
      activities were evaluated in the left primary somatosensory cortex (S1), left
      (S2(L)) and right (S2(R)) secondary somatosensory cortex, anterior cingulate
      cortex (ACC) and posterior cingulate cortex (PCC). Ipsilateral hand muscle
      contraction was associated with a decrease of source activity in S1 and with
      subsequent increases in S2(L) and the PCC. Contralateral hand muscle contraction
      was accompanied by a decrease of source activity in bilateral S2 cortices
      followed by decreases in the S1 and anterior cingulate cortex. Results suggest
      early suppression of source activity in S1 during ipsilateral hand muscle
      contractions and in bilateral S2 during contralateral hand muscle contractions.

PMID- 15998567
TI  - Combined efficacies of DL-alpha-lipoic acid and meso 2,3 dimercaptosuccinic acid
      against arsenic induced toxicity in antioxidant systems of rats.
AB  - Health hazards caused by heavy metals have become a great concern to the
      population. Arsenic as an environmental agent is considered to be a toxic
      substance due to its carcinogenic potential in humans. Since arsenic compounds
      might exert their toxicity by the generation of reactive oxygen species, we have
      evaluated the effect of both DL-alpha-lipoic acid (LA) and meso 2,3 dimercapto
      succinic acid (DMSA) on the antioxidants and lipid peroxidation in arsenic
      treated rats. The objective of the study was to determine whether DL-alpha-lipoic
      acid and meso 2,3 dimercapto succinic acid could rehabitate antioxidant depletion
      and damage to biomolecules in protection against oxidative insults. A significant
      increase in the levels of reactive oxygen species formation and lipid
      peroxidation and decrease in the activities of antioxidant enzymes were observed
      in arsenic exposed rats. Supplementation of DL-alpha-lipoic acid and meso 2,3
      dimercapto succinic acid to arsenic fed rats significantly increased the
      activities of superoxide dismutase, catalase, glutathione peroxidase with
      elevation in the levels of reduced glutathione, total sulfhydryl, ascorbic acid
      and alpha-tocopherol. In addition, significant decrease in the levels of reactive
      oxygen species formation and lipid peroxidation was also observed in our study.
      From our results, we conclude that DL-alpha-lipoic acid and meso 2,3 dimercapto
      succinic acid play a synergistic role in decreasing arsenic induced oxidative
      damage by elevating the antioxidant status in liver and kidney.

PMID- 15998568
TI  - A putative autosomal gene increasing ovulation rate in Romney sheep.
AB  - Ovulation rates were measured in 547 progeny of 24 rams in a Romney flock with a
      long history of high prolificacy. These sheep were from the same family line and
      the distribution of ovulation rates suggests the presence of a segregating major
      gene (FecW) that increases prolificacy. The phenotype differs from those
      previously described for major genes affecting prolificacy in sheep. The putative
      gene shows autosomal inheritance and one copy increases ovulation rate by 0.8-1.0
      eggs per ewe ovulating. To date, we have found no evidence of infertility among
      putative homozygous ewes, as described in some autosomal major genes for
      prolificacy.

PMID- 15998569
TI  - Preparation of coated nanoparticles for a new mucosal vaccine delivery system.
AB  - It has been found that the adsorption of antigens onto chitosan particles is an
      easy and unique mild loading process suitable to be used with vaccines. In order
      to increase the stability of this particles and to prevent an immediate
      desorption in gastrointestinal fluids, a coating process with sodium alginate was
      developed. One of the challenges of this developing process was to keep the
      particles in the nanosized range in order to be taken up by M-cells of the
      Peyer's patches. The observed inversion of the particles' zeta potential values
      after coating suggested the presence of an alginate coating layer. These results
      were confirmed by FTIR and DSC techniques. Additionally, in vitro release studies
      showed that the presence of the alginate layer around the particles was able to
      prevent a burst release of loaded ovalbumin and to improve the stability of the
      nanoparticles in simulated intestinal fluid at 37 degrees C. The optimisation of
      the coating process resulted in 35% (w/w) for the loading capacity of the coated
      particles. SEM investigations confirmed a suitable size of the coated
      nanoparticles for the uptake by M-cells.

PMID- 15998570
TI  - Ginkgo biloba extracts for tinnitus: More hype than hope?
AB  - The investigation into the effects of Ginkgo biloba extracts on tinnitus has
      suffered from a dearth of effective animal models as well as systematic clinical
      trials employing double-blind and placebo-controlled designs. Some clinical
      trials have yielded positive results, however, these studies are few and have
      been limited either by design flaws, the small size of the significant effects,
      or else the results have not been published in peer-reviewed journals and
      therefore the quality of the research is not assured. By contrast, the two most
      systematic clinical trials, both double-blind and placebo controlled, and
      published in respected peer-reviewed journals, have yielded negative results and
      suggest that Ginkgo biloba extracts are of little more use in the treatment of
      tinnitus than a placebo. Treatments for tinnitus that do not have therapeutic
      efficacy not only waste money but can potentially prevent patients from seeking
      therapy that is efficacious. Furthermore, the unsupervised use of Ginkgo biloba
      extracts with other medications could lead to adverse side effects which are
      unnecessary and not justified in terms of therapeutic benefit.

PMID- 15998571
TI  - Total flavones from Elsholtzia blanda reduce infarct size during acute myocardial
      ischemia by inhibiting myocardial apoptosis in rats.
AB  - Apoptosis is a common pathological feature in acute myocardial infarction (AMI).
      The infarct size is an important determinant of the prognosis of AMI. In recent
      years, Chinese medicinal herbs and their extracts have received great attention
      in prevention of AMI. The aim of this investigation was to evaluate the anti
      ischemic effect of total flavones from Elsholtzia blanda (Benth.) Benth. (TFEB),
      a traditional Chinese medicine and to make clear the mechanism involved in it.
      Myocardial infarction was induced by coronary occlusion in rats. Apoptosis was
      measured quantitatively by the terminal transferase UTP nick end-labeling (TUNEL)
      method and confirmed by DNA laddering on agarose gel. The expression of anti
      apoptotic protein, Bcl-2 and pro-apoptotic protein, Bax was visualized by Western
      blot analysis. TFEB significantly reduced infarct size and TUNEL-positive rate
      confirmed by disappearance of DNA laddering. Greater Bcl-2 and attenuated Bax
      expression was found in TFEB treating rats. These results suggest that TFEB
      reduce infarct size during AMI by inhibiting myocardial apoptosis through
      modulation of Bcl-2 family.

PMID- 15998572
TI  - Short tandem repeat (STR) genotyping of keratinised hair. Part 2. An optimised
      genomic DNA extraction procedure reveals donor dependence of STR profiles.
AB  - A feasibility study of short tandem repeat (STR) genotyping of telogen phase
      hairs in particular, and hair shaft in general, is presented. A number of
      extraction procedures in common use were investigated and the quantities of
      nuclear DNA (nuDNA) delivered were quantified via a real-time PCR assay. The
      extracts were subjected to two variations on AmpFlSTR Profiler Plus PCR
      amplification strategies (extended cycles, two rounds of PCR) and the genotypes
      compared. Nuclear DNA was found to persist in human hair shafts, albeit at very
      low levels. Full Profiler Plus profiles consistent with the hair donor were
      obtained from 100 mg hair shaft samples (bleached and unbleached). These were,
      however, mixed profiles, indicating low copy number (LCN) contamination in the
      extracts. Single telogen hair clubs and single hair shafts delivered partial
      profiles with usually only one allele of heterozygous loci. Telogen phase hairs
      yielded the same amount of nuDNA (and no more) as hair shafts (either anagen or
      telogen). Whether hair shafts dissolved or not in lysis buffer had no effect on
      either the quantitated yield of DNA or on the chance of obtaining a correct
      genotype. These results provide evidence that genomic DNA resides on the exterior
      of the hair shaft and we use this information to suggest an optimal procedure for
      nuDNA extraction from keratinised hair samples: soaking hairs in simple digestion
      buffers containing Tris-HCl, a salt and a chelating agent without prior cleaning
      of the hair shafts. It is proposed that cleaning removes most of the recoverable
      DNA. This procedure was applied to obtain genotypes from 3 cm hair shafts which
      matched reference profiles from the donors at up to 9 out of 10 AmpFlSTR Profiler
      Plus STR loci. When the genotyping success was measured by counting the number of
      matches between the two dominant alleles at each locus for each extract with the
      reference DNA profile of the hair donor, the success was found to be highly
      dependent on the donor. The number of matching alleles varied between not less
      than 10 for one donor to no more than two for another donor. These results may
      well be linked to the environmental experience of the hairs from each donor prior
      to removal.

PMID- 15998573
TI  - Iranian STR variation at the fringes of biogeographical demarcation.
AB  - The integrative relationship between population genetics and forensic biology
      allows for a thorough genetic characterization of extant human populations. This
      study aimed to genetically characterize 150 unrelated healthy donors from a
      general population in Iran both forensically and phylogenetically. The allelic
      frequencies of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01,
      D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were
      generated. This constitutes the core of polymerase chain reaction (PCR)-based DNA
      genetic markers in the US Combined DNA Index System (CODIS) plus two additional
      loci (D2S1338 and D19S433) that together are consistent with several other
      worldwide database requirements. There were no deviations from Hardy-Weinberg
      expectations. Based upon the allelic frequencies, several important forensic
      parameters were calculated including: gene diversity (GD) index, power of
      discrimination (PD), polymorphic information content (PIC) and power of exclusion
      (PE). G-tests indicate the allelic frequencies of the Iranians are statistically
      non-significant compared to two Turkish populations yet, statistically different
      from the remaining 18 groups obtained from the literature and examined in this
      study. This suggests that the Iranian dataset may be forensically equivalent to
      the dataset from the Turkish region of Eastern Anatolia and the general
      population from Turkey. Phylogenetic analysis of our population with the full set
      of 15 loci indicate the Iranians occupy an intermediate position relative to the
      major Caucasian and East Asian clades on a global level. A regional phylogenetic
      analysis using 13 of the 15 loci indicate the Iranians segregate in a more
      compact association with groups from southeastern Spain, Arabs from Morocco and
      Syria, and especially with the general population from Turkey and those from
      Eastern Anatolia. These groups are flanked by highly differentiated populations
      from northern India and a Berber group from Tunisia on opposing ends of the
      regional phylogram. This report also demonstrates the necessity to thoroughly
      characterize the genetic composition of populations located in geographic
      intersections in order to choose the appropriate dataset on which to base
      forensic calculations, not only at an intra-population level, but also at an
      inter-population level as well.

PMID- 15998574
TI  - A 9-loci Y chromosome haplotype in three Italian populations.
AB  - Three geographic areas of Italy have been sampled and genotyped for 9 Y
      chromosome STRs: DYS19, DYS385, DYS388, DYS389 I and II, DYS390, DYS391, DYS392,
      DYS393. Sampling was focused on residents of small areas, well distant from major
      urban centres. Only individuals whose grandfather would live in the same area
      were included. A total of 210 unrelated individuals were collected. Distribution
      of genetic variation across the three samples and comparison with previously
      published Italian database indicated that so far Y chromosome diversity has been
      only partially explored in the Italian Peninsula.

PMID- 15998575
TI  - Different response of senescent female Sprague-Dawley rats to gemfibrozil and
      rosiglitazone administration.
AB  - Eighteen-month-old Sprague-Dawley rats present age-related alterations in lipid
      and glucose metabolism and are resistant to the effect of PPARalpha-activating
      hypolipidemic drugs, such as gemfibrozil. We tested if these animals were
      responsive to the administration of rosiglitazone, an insulin-sensitizer acting
      on PPARgamma. We determined in 18-month-old female Sprague-Dawley rats treated
      for 21 days with a daily dose of 3mg gemfibrozil/kg or 3mg rosiglitazone/kg: (i)
      plasma concentrations of total cholesterol (TC), triglycerides (TG),
      nonesterified fatty acids (NEFA), glucose, insulin and leptin, (ii) hepatic
      concentrations of TG, NEFA and cholesteryl esters (CE), and (iii) the liver
      expression and binding activity of peroxisome proliferator-activated receptor
      alpha (PPARalpha), and several of its target genes, hepatic nuclear factor-4 (HNF
      4), and liver X receptor alpha (LXRalpha). Although gemfibrozil induced mild
      effects on hepatic PPARalpha, HNF-4, and LXRalpha, only rosiglitazone
      significantly reduced plasma TG (59%), glucose (19%), insulin (61%), and leptin
      (66%), and liver TG (43%), CE (49%), and NEFA (27%). These changes were
      associated to an increased body weight gain and a decrease in visceral fat (8.7
      fold and 37% vs. control females, respectively). The beneficial effect of
      rosiglitazone treatment in 18-month-old female rats could be related to a direct
      effect on white adipose tissue.

PMID- 15998576
TI  - Follicular fluid concentration of transforming growth factor-beta1 is negatively
      correlated with estradiol and follicle size at the early stage of development of
      the first-wave cohort of bovine ovarian follicles.
AB  - The objectives of this study were to characterize the relationship between
      estradiol and transforming growth factor-beta1(TGF-beta1) concentrations in
      follicular fluid of growing bovine ovarian follicles, and to examine the effect
      of TGF-beta1 on FSH-stimulated estradiol secretion in cultured bovine granulosa
      cells. Follicular fluid was collected from individual follicles >5 mm in diameter
      by ultrasound-guided transvaginal puncture (n = 12 heifers). Follicles were
      sampled at four different stages of development of the first post-ovulatory wave
      during selection of the single dominant follicle. Estradiol, progesterone and
      total TGF-beta1 were measured in follicular fluid of the three or four largest
      follicles sampled when the largest follicle (F1) had reached either 6.5, 7.5, 8.5
      or 9.5+/-0.5 mm stage of development. There was a significant negative
      relationship between follicular fluid TGF-beta1 and estradiol concentrations (R2
      = 0.44; p < 0.002), and between TGF-beta1 concentrations and follicle diameter
      (R2 = 0.23; p < 0.01) in cohort follicles at the 6.5 mm stage, but not at any
      later stage of development of the follicle wave. There was no correlation between
      progesterone and TGF-beta1 concentrations at any stage. To assess the causal
      relationship between TGF-beta1 and estradiol, granulosa cells from follicles
      measuring 2-5 mm at dissection were placed in serum-free culture. TGF-beta1
      caused a dose-dependent decrease in FSH-stimulated estradiol secretion (P <
      0.001). These findings suggest that TGF-beta1 has an inhibitory effect on
      estradiol secretion in FSH-stimulated follicles and that a reduction in TGF-beta1
      inhibition may be part of the mechanism of selection of a single dominant
      follicle.

PMID- 15998577
TI  - Construction and virulence of a Pasteurella multocida fhaB2 mutant in turkeys.
AB  - Pasteurella multocida is the causative agent of fowl cholera. The organism can
      occur as a commensally in the naso-pharyngeal region of apparently healthy
      animals and it can be a primary or secondary pathogen in the disease process of
      birds. The complete genome of an avian strain of P. multocida has been sequenced
      and was shown to possess two filamentous hemagglutinin genes designated fhaB1 and
      fhaB2. Filamentous hemagglutinin transposon mutants of a bovine strain of P.
      multocida are attenuated in mice. Here, we report the construction of an fhaB2 P.
      multocida mutant in an avian strain P-1059 (A:3). The fhaB2 mutant and the parent
      were assessed for virulence in turkeys by intranasal and intravenous challenge.
      Inactivation of fhaB2 resulted in a high degree of attenuation when turkeys were
      challenged intranasally and to a lesser degree when intravenously administered.
      Resistance of the fhaB2 mutant and parent strain to killing by serum complement
      was similar.

PMID- 15998578
TI  - The load of Chlamydia pneumoniae in the Alzheimer's brain varies with APOE
      genotype.
AB  - Studies from this laboratory have indicated that the intracellular eubacterial
      respiratory pathogen Chlamydophila (Chlamydia) pneumoniae is commonly found in
      brain regions displaying characteristic neuropathology in patients with late
      onset Alzheimer's disease (AD) but not in congruent samples from non-AD control
      individuals. In later work, we provided evidence suggesting that some
      relationship exists between the APOE epsilon4 gene product and the pathobiology
      of this organism. In the present report, in situ hybridization analyses indicated
      that the number of C. pneumoniae-infected cells in affected brain regions of
      epsilon4-bearing AD patients was higher overall than that in congruent brain
      regions from AD patients lacking that allele. Quantitative real-time PCR analyses
      of AD brain tissue samples demonstrated that actual bacterial burden in those
      samples varied over several orders of magnitude, but that samples from epsilon4
      bearing patients did have significantly higher bacterial loads than did congruent
      samples from patients without the allele (ANOVA, p<0.05). These results may
      explain in part the observations that epsilon4-bearing individuals have a higher
      risk of developing AD, and that such patients progress more rapidly to cognitive
      dysfunction than do individuals lacking this allele.

PMID- 15998579
TI  - Physician-parent communication as predictor of parent satisfaction with child
      development services.
AB  - The purpose of this study was to assess the level of parental satisfaction with
      services of a child development center and to evaluate the physician-parent
      dimensions of communication. A total of 90 parents to children with disability
      ranging in age from 6 months to 6 years participated in the study (84% response
      rate). Attitudes regarding parental communication with physicians were evaluated
      by 15 items clustered into three factors, which expressed different dimensions of
      communication: caring, collaboration and interest. Parents ranked their general
      satisfaction with the center's services relatively high as well as their
      evaluations of physician behavior of caring, collaboration and interest. Positive
      and statistically significant correlations were found between the studied
      communication dimensions and general satisfaction. However, collaboration was the
      only dimension that explained the variability on general satisfaction in a
      multivariate analysis. The collaboration of the physician with the parents was a
      key factor to explain parental general satisfaction with child rehabilitative
      services. Collaboration, which is associated with processes such as mutual
      decision making and sharing of responsibility, should be nurtured, in order to
      increase parents' general satisfaction with the services given.

PMID- 15998580
TI  - Complete deficiencies of complement C4A and C4B including 2-bp insertion in codon
      1213 are genetic risk factors of systemic lupus erythematosus in Thai
      populations.
AB  - The complement component C4 is encoded by two genes: C4A and C4B on human
      chromosome 6p in the major histocompatibility complex (MHC). Most studies have
      linked the deficiencies in C4 with systemic lupus erythematosus (SLE) in Angio
      Irish, North American, Black American, Mexican American, Australian and Japanese
      populations. Null alleles at either locus (C4AQ0 or C4BQ0) are relatively common
      in Americans occurring at the C4A and C4B loci in approximately 10% and 16% of
      normal individuals, respectively. In the present study, we extensively examined
      the possible association between homozygous C4Q0 and SLE in a large cohort of
      Thai populations diagnosed as SLE and further attempted to identify the genetic
      basis of C4Q0. One hundred and eighteen cases of SLE patients and 145 matched
      controls were genotyped by touchdown PCR. The results confirmed the previous
      studies that 5.93% (7/118) of C4 null genes: 2.54% (3/118) of C4AQ0 and 3.39%
      (4/118) of C4BQ0 were found in SLE patients. In contrast to other studies, we
      found no cases of C4 null genes in normal control (0 from 145 samples). To
      further investigate the genetic basis of C4 deficiency, all genomic DNAs were
      also analyzed for 2-bp (TC) insertion at codon 1213 in exon 29 which is a common
      mutation in many C4A null genes and a novel 1-bp deletion (C) at codon 522 in
      exon 13 that is common in most C4B null genes. Both mutation results in a flame
      shift mutation and premature stop codon using sequence specific primers PCR (SSP
      PCR) and direct sequencing. The results showed that there was 2-bp insertion in
      exon 29 of mutant C4B gene in one SLE patient carrying C4AQ0. There was no 2-bp
      insertion in exon 29 of both C4A and C4B genes in normal individual and the rest
      of SLE patients. All patients with C4AQ0 exhibited more than 5 ACR criteria
      including malar rash, oral ulcers, renal disorder, immunological disorder, anti
      nuclear antibody, without hematological disorder. In contrast, all of C4BQ0 SLE
      patients showed 5 or 6 ACR criteria including hematological disorder, malar rash,
      oral ulcers, renal disorder, immunological disorder and anti-nuclear antibody. A
      patient who possesses C4AQ0 and 2-bp insertion in exon 29 of mutant C4B showed 9
      ACR criteria but no discoid rash and hematological disorder. In conclusion, both
      C4AQ0 and C4BQ0 are the strong predisposing factors for SLE in Thais. It was
      supported by the absence of either C4A or C4B deletion in healthy control. We
      suggested that the different racial and genetic backgrounds could alter the
      thresholds for requirement of C4A or C4B protein levels in immune tolerance and
      regulation.

PMID- 15998581
TI  - Genetic and functional association of the immune signaling molecule 4-1BB
      (CD137/TNFRSF9) with type 1 diabetes.
AB  - Idd9.3, a locus that determines susceptibility to the autoimmune disease type 1
      diabetes (T1D) in the nonobese diabetic (NOD) mouse, has been mapped to the
      distal region of chromosome 4. In the current report we reduce the size of the
      Idd9.3 interval to 1.2Mb containing 15 genes, including one encoding the immune
      signaling molecule, 4-1BB, which shows amino acid variation between diabetes
      sensitive and resistant strains. 4-1BB, a member of the TNF receptor superfamily
      expressed by a variety of immune cells, mediates growth and survival signals for
      T cells. Functional analyses demonstrate that purified T cells from NOD congenic
      mice with the C57BL/10 (B10) allele at Idd9.3 produce more IL-2 and proliferate
      more vigorously in response to anti-CD3 plus immobilized 4-1BB ligand than T
      cells from NOD mice with the NOD allele at Idd9.3. In contrast, the response to
      anti-CD3 plus anti-CD28 costimulation was indistinguishable between the congenic
      strains, pinpointing the differences in NOD versus NOD.B10 Idd9.3 T cell
      responses to the 4-1BB costimulatory pathway. These data provide evidence in
      support of Idd9.3 as the locus encoding 4-1BB and suggest that the 4-1BB
      signaling pathway could have a primary function in the etiology of autoimmune
      disease.

PMID- 15998582
TI  - Comparison of voxel-based 3-D MRI analysis and subtraction ictal SPECT
      coregistered to MRI in focal epilepsy.
AB  - While voxel-based 3-D MRI analysis methods as well as assessment of subtracted
      ictal versus interictal perfusion studies (SISCOM) have proven their potential in
      the detection of lesions in focal epilepsy, a combined approach has not yet been
      reported. The present study investigates if individual automated voxel-based 3-D
      MRI analyses combined with SISCOM studies contribute to an enhanced detection of
      mesiotemporal epileptogenic foci. Seven consecutive patients with refractory
      complex partial epilepsy were prospectively evaluated by SISCOM and voxel-based 3
      D MRI analysis. The functional perfusion maps and voxel-based statistical maps
      were coregistered in 3-D space. In five patients with temporal lobe epilepsy
      (TLE), the area of ictal hyperperfusion and corresponding structural
      abnormalities detected by 3-D MRI analysis were identified within the same
      temporal lobe. In two patients, additional structural and functional
      abnormalities were detected beyond the mesial temporal lobe. Five patients with
      TLE underwent epileptic surgery with favourable postoperative outcome (Engel
      class Ia and Ib) after 3-5 years of follow-up, while two patients remained on
      conservative treatment. In summary, multimodal assessment of structural
      abnormalities by voxel-based analysis and SISCOM may contribute to advanced
      observer-independent preoperative assessment of seizure origin.

PMID- 15998583
TI  - URB expression in human dermal papilla cells.

PMID- 15998584
TI  - Complicated parapneumonic effusion and empyema thoracis: microbiologic and
      therapeutic aspects.
AB  - Patients with pleural infections have a high risk of morbidity and mortality with
      prolonged hospitalization. The best methods for treating pleural infections
      remain debatable. Although the increasing drainage volume effect of streptokinase
      adjunctive to chest-tube, is well known, its effect on clinical outcomes like
      duration of hospitalization and need for further surgery, remains controversial.
      The aim of this study was to analyze the etiological and microbiological factors
      for pleural infections, and assess the effect of streptokinase adjunctive to
      chest tube for clinical outcomes. Charts of patients with a chest disease
      department discharge diagnosis of complicated parapneumonic effusion or empyema
      were retrospectively reviewed. Of the 107 patients (85 male), the mean age was
      47.9+/-17.1 years. The most frequently shown bacteriological agent was
      Staphylococcus aureus. Drainage with thoracentesis was used in 44 patients (group
      1); chest tube was performed in 44 patients (group 2) and intrapleural
      streptokinase was given after chest tube insertion in 19 patients (group 3). Mean
      hospitalization time in group 1 was shorter than the other two groups (P<0.05),
      but there was no significant difference between group 2 and 3. Our mortality rate
      was 8.4%. Success rates were 95.4%, 65.9% and 78.5% in groups 1, 2, and 3,
      respectively (P>0.05). Intrapleural streptokinase is a safe procedure but it did
      not effect the duration of hospitalization, mortality and success rate. Mortality
      remains especially high in patients with concomitant disease.

PMID- 15998585
TI  - Characterisation of patients with frequent exacerbation of asthma.
AB  - BACKGROUND: Exacerbation is one of the most significant problems in patients with
      asthma. Although subpopulation of patients is more susceptible to exacerbations
      than others, which clinical features characterise susceptibility to exacerbation
      are not well understood. METHODS: Consecutive non-smoking adult patients with
      asthma who had multiple exacerbations (ME) despite regular maintenance treatment
      were compared with those who had at most single exacerbation as control during
      the previous 1 year. Exacerbation of asthma is defined initiations or escalations
      of systemic corticosteroid as part of the management for aggravated asthma
      condition. RESULTS: Patients with ME (n=32, male: 6, mean age: 46.7 years) were
      characterised by intensive current maintenance treatment (dose of inhaled
      corticosteroid; 1037.5+/-452.8 vs 621.6+/-257.3 microg, P=0.0005, proportion of
      oral corticosteroid users; 28.1% vs 2.7%, P=0.008), severe episodes of
      exacerbation (asthma-related hospitalisations; 71.9% vs 23.4%, P=0.0002, arrival
      on ambulance; 37.5% vs 8.1%, P=0.008), concomitant chronic sinusitis (34.4% vs
      10.8%, P=0.038) and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs)
      (34.4% vs 5.4%, P=0.006) in comparison with controls (n=37, male:11, mean
      age:44.4). Pulmonary function in patients with ME was characterised by persistent
      airflow limitation and reduced reversibility. CONCLUSION: Patients with ME are at
      increased risk for severe exacerbation despite more intensive maintenance anti
      inflammatory treatment. Persistent irreversible airflow limitation and
      complications of chronic sinusitis and/or NSAIDs intolerance are characteristics
      to this subpopulation.

PMID- 15998586
TI  - Electrochemical determination of gamma-glutamyl transpeptidase activity and its
      application to a miniaturized analysis system.
AB  - A novel method to determine the activity of gamma-glutamyl transpeptidase (gamma
      GTP) was developed. gamma-l-glutamyl-l-glutamate and glycyl-glycine were used as
      the substrates for gamma-GTP. l-glutamate produced by the enzymatic reaction was
      measured with an amperometric l-glutamate sensor. Following the mixing of the
      substrate solution and a sample solution, the current generated on the l
      glutamate sensor continued to increase at a constant rate. The method was used to
      construct a miniaturized analysis system for the determination of gamma-GTP
      activity. The system consisted of the l-glutamate sensor formed on a glass
      substrate and a polydimethylsiloxane (PDMS) flow channel. Since the l-glutamate
      concentration in the solution increased as the solution was mobilized through the
      flow channel, a constant current increase was observed. The relation between the
      slope of the response curve and the activity of gamma-GTP was linear between 35 U
      l(-1) and 659 U l(-1). The rate analysis in the micro flow channel minimized the
      influence of interferents. The reproducibility of the output of the micro system
      was found to be good with a relative standard deviation (R.S.D.) of 5.6% at 659 U
      l(-1). The activities of gamma-GTP in human serum samples were also determined
      and compared with values obtained with a conventional spectroscopic method. The
      values obtained by the two methods were consistent with a correlation coefficient
      of 0.953.

PMID- 15998587
TI  - Serum levels of IGF-1 and IGFBP-3 during adjuvant chemotherapy for primary breast
      cancer.
AB  - High serum concentrations of insulin-like growth factor-1 (IGF-1) are associated
      with an increased risk of breast, prostate, colorectal, and lung cancer whereas
      IGF binding protein-3 (IGFBP-3) seems to exert a protective effect. Therefore,
      patients may benefit from low IGF-1 levels and high IGFBP-3 levels. This study
      evaluated whether adjuvant anthracycline-containing chemotherapy modulates IGF-1
      and/or IGFBP-3 serum levels in breast cancer patients. In 18 patients undergoing
      adjuvant treatment for primary breast cancer, IGF-1 and IGFBP-3 serum levels were
      measured with immunoassays during chemotherapy regimens of either 5-fluorouracil,
      epirubicin and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC).
      Mean pre-treatment values of IGF-1 and IGFBP-3 were 124+/-13 and 3698+/-186
      ng/ml, respectively. No significant changes in IGF-1 and IGFBP-3 serum
      concentrations were observed during adjuvant anthracycline-containing
      chemotherapy. IGF-1 levels significantly correlated with IGFBP-3 levels before
      and during chemotherapy. In conclusion, these chemotherapy regimens do not seem
      to modulate IGF-1 or IGFBP-3 levels in a favourable or unfavourable way.

PMID- 15998589
TI  - The role of tamoxifen in the management of gynaecomastia.
AB  - Gynaecomastia affects half of the male population at some stage in their life.
      Only a small proportion of them would require treatment for cosmetic appearance
      or to relieve pain and tenderness. Recently, tamoxifen has shown some promising
      results in the management of gynaecomastia. To assess the efficacy of tamoxifen,
      we carried out a retrospective study of all men treated for gynaecomastia with
      particular emphasis on those treated medically. Men with painful gynaecomastia
      were given 10 mg of tamoxifen for 3 months. Response to treatment was categorised
      as good, moderate and no response. Thirteen men (median age 36) were placed on
      tamoxifen. Ten patients responded well to tamoxifen. One patient developed calf
      tenderness and stopped the medication. No other adverse effects were reported.
      Two patients could not be followed up. Tamoxifen appears safe and effective in
      men with painful idiopathic or physiological gynaecomastia and should be
      considered as an initial option before contemplating surgery.

PMID- 15998588
TI  - Bilateral breast enlargement due to Trichophyton rubrum.
AB  - Gynecomastia is the most common cause of breast enlargement in males.
      Trichophyton rubrum is a common dermatophyte, is responsible for a variety of
      infections, and may rarely manifest as a dermatophytic pseudomycetoma. We report
      the case of a 52-year-old man who presented with progressive bilateral breast
      enlargement. This is the first reported case of bilateral breast pseudomycetoma
      due to T. rubrum. Long-term antifungal therapy with itraconazole was successful.

PMID- 15998590
TI  - Monte Carlo simulations to estimate the background spectrum in a shielded NaI(Tl)
      gamma-spectrometric system.
AB  - The paper describes a Monte Carlo simulation technique to estimate the background
      gamma-radiation for a low-level counting setup with NaI(Tl) detector inside an
      iron shield box. With monoenergetic gamma-sources ranging from 300 to 2000 keV at
      intervals of 100 keV we have got a matrix of transmitted flux data calculated
      using a general purpose Monte Carlo code. The intrinsic efficiency of the
      detector is also calculated. This matrix of data is folded with the measured
      spectrum outside the setup to estimate the observed spectrum in the NaI(Tl)
      detector. We have studied various combinations of splitting and Russian roulette
      to arrive at an optimal combination based on the figure of merit of the Monte
      Carlo results. The observed discrepancy between the measured and calculated
      spectra is mainly due to porosity of the iron shield box.

PMID- 15998591
TI  - Concentration and characteristics of depleted uranium in water, air and
      biological samples collected in Serbia and Montenegro.
AB  - During the Balkan conflicts, in 1995 and 1999, depleted uranium (DU) rounds were
      employed and were left in the battlefield. Health concern is related to the risk
      arising from contamination of the environment with DU penetrators and dust. In
      order to evaluate the impact of DU on the environment and population in Serbia
      and Montenegro, radiological surveys of DU in water, air and biological samples
      were carried out over the period 27 October-5 November 2001. The uranium isotopic
      concentrations in biological samples collected in Serbia and Montenegro, mainly
      lichens and barks, were found to be in the range of 0.67-704 Bqkg(-1) for (238)U,
      0.48-93.9 Bqkg(-1) for (234)U and 0.02-12.2 Bqkg(-1) for (235)U, showing uranium
      levels to be higher than in the samples collected at the control sites. Moreover,
      (236)U was detectable in some of the samples. The isotopic ratios of
      (234)U/(238)U showed DU to be detectable in many biological samples at all
      examined sites, especially in Montenegro, indicating widespread ground-surface DU
      contamination, albeit at very low level. The uranium isotopic concentrations in
      air obtained from the air filter samples collected in Serbia and Montenegro were
      found to be in the range of 1.99-42.1 microBqm(-3) for (238)U, 0.96-38.0
      microBqm(-3) for (234)U, and 0.05-1.83 microBqm(-3) for (235)U, being in the
      typical range of natural uranium values. Thus said, most of the air samples are
      DU positive, this fact agreeing well with the widespread DU contamination
      detected in the biological samples. The uranium concentrations in water samples
      collected in Serbia and Montenegro were found to be in the range of 0.40-21.9
      mBql(-1) for (238)U, 0.27-28.1 mBql(-1) for (234)U, and 0.01-0.88 mBql(-1) for
      (235)U, these values being much lower than those in mineral water found in
      central Italy and below the WHO guideline for drinking water. From a
      radiotoxicological point of view, at this moment there is no significant
      radiological risk related to these investigated sites in terms of possible DU
      contamination of water, air and/or plants.

PMID- 15998592
TI  - Molecular identification and expression analysis of natural resistance associated
      macrophage protein (Nramp) cDNA from Japanese flounder (Paralichthys olivaceus).
AB  - Natural resistance associated macrophage protein (Nramp) controls partially
      innate resistance to intracellular parasites. Its function is to enhance the
      ability of macrophages to kill pathogens. However, little is known about the
      structure and function of Nramp in lower vertebrates such as teleosts. We have
      recently isolated a cDNA encoding Nramp from Japanese flounder (Paralichthys
      olivaceus). The full-length cDNA of the Nramp is 3066 bp in length, including 224
      bp 5' terminal UTR, 1662 bp encoding region and 1180 bp 3' terminal UTR. The 1662
      nt open reading frame was found to code for a protein with 554 amino acid
      residues. Comparison of amino acid sequence indicated that Japanese flounder
      Nramp consists of 12 transmembrane (TM) domains. A consensus transport motif
      (CTM) containing 20 residues was observed between transmembrane domains 8 and 9.
      The deduced amino acid sequence of Japanese flounder had 77.30%, 82.71%, 82.67%,
      79.64%, 80.72%, 90.97%, 91.16%, 60.14%, 71.48%, 61.69%, 72.37% identity with that
      of rainbow trout Nramp alpha and beta, channel catfish Nramp, fathead minnow
      Nramp, common carp Nramp, striped sea bass Nramp, red sea bream Nramp, mouse
      Nramp 1 and 2, human Nramp 1 and 2, respectively. RT-PCR indicated that Nramp
      transcripts were highly abundant in spleen, head kidney, abundant in intestine,
      liver and gill, and less abundant in heart. The level of Nramp mRNA in embryos
      gradually increases during embryogenesis from 4 h (8 cell stage) to 80 h (hatched
      stage) after fertilization.

PMID- 15998593
TI  - Hypocretin/orexin: maintenance of wakefulness and a multiplicity of other roles.

PMID- 15998594
TI  - Pharmacotherapy in complicated parapneumonic pleural effusions and thoracic
      empyema.
AB  - Parapneumonic pleural effusions (PPE) and pleural empyema (PE) present a
      frequently diagnostic and therapeutic challenge in clinical practice. Although
      pleural diseases have received increased attention during the past decade, there
      are still many unanswered questions concerning the diagnosis and treatment of PPE
      and PE. A lack of controlled studies concerning the management of PPE and PE was
      noted in recent guidelines. The use of fibrinolytics intrapleurally appears to
      enhance intercostals tube drainage, reducing the requirement for subsequent
      surgical mechanical debridement. Recently, there has been interest in other
      intrapleural agents including combination drugs consisting of streptokinase and
      streptodornase-alpha, Dnase. Factors to be considered in evaluating whether or
      not intrapleural instillation of fibrinolytics is effective include an assessment
      of clinical responses. This review discusses the use of fibrinolytic agents as a
      novel therapeutic options for treating the various stages of parapneumonic
      effusions and empyemas.

PMID- 15998595
TI  - A comparison of symptomatic and asymptomatic office workers performing monotonous
      keyboard work--1: neck and shoulder muscle recruitment patterns.
AB  - Work-related neck and upper limb disorders (WRNULD) are common problems among
      office workers who use computers intensively and maintain prolonged static
      postures. These disorders have often been attributed to result from sustained
      muscle activity in the neck-shoulder musculature. The present study examined
      whether symptomatic subjects exhibited the same muscle activity patterns as
      asymptomatic controls when they performed a prolonged computer task under the
      same conditions. Surface electromyography (EMG) of four major neck-shoulder
      muscles were compared between a Case Group (n=23) and a Control Group (n=20) of
      female office workers. The Case Group had higher activity in the right upper
      trapezius (UT) while the Control Group had more symmetrical muscle activity
      between left and right UT. The Case subjects could also be differentiated into
      "High Discomfort" and "Low Discomfort" sub-groups based on their discomfort
      scores. The High Discomfort Group had significantly higher right UT activity
      compared to the Low Discomfort and Control Groups. Results suggested that
      symptomatic individuals had altered muscle recruitment patterns that persisted
      throughout the sustained occupational task, while discomfort increased with time
      at-task. These findings indicate that altered muscle recruitment patterns
      observed in the symptomatic subjects preceded the onset of task discomfort, and
      this finding may have important implications for the etiology of WRNULD.

PMID- 15998597
TI  - Effect of ionizing radiation on the pteridine metabolic pathway and evaluation of
      its cytotoxicity in exposed hospital staff.
AB  - Investigations carried out to estimate the effect of long-term occupational
      exposure to low levels of external ionizing radiation indicated that exposed
      hospital staff showed an increase in chromosome aberrations. The purpose of this
      study was to evaluate whether genomic instability or an alteration in pteridine
      synthesis could be used as a marker of the potential hazard of ionizing radiation
      in hospital workers. Twenty gamma-radiation- and 33 X-ray-exposed technicians
      working in radiotherapy and radio-diagnostic units were included in this study,
      along with 22 healthy matched individuals. Plasma concentrations of nitrite plus
      nitrate (NO(x)) were measured to estimate reactive nitrogen species. Urinary
      neopterin, biopterin and creatinine concentrations were measured by high
      performance liquid chromatography to determine metabolic activity along the
      pteridine pathway. Sister chromatid exchange was used as a measure of
      mutagenicity. Apoptosis was evaluated morphologically and also with a DNA
      fragmentation test. The plasma NO(x) levels of both gamma-radiation- and X-ray
      exposed technicians were significantly higher than those of the healthy controls
      (p<0.05). While the urinary biopterin concentrations were significantly higher in
      radiation-exposed groups compared with the healthy subjects (p<0.05), urinary
      neopterin concentrations remained unchanged. The apoptosis rates of gamma
      radiation- and X-ray-exposed workers were significantly elevated in comparison
      with those in the control group (both p<0.05). Also, the increase in sister
      chromatid exchange frequency was significant in each of the radiation-exposed
      groups (exposed groups versus controls; p<0.05). These results indicate that long
      term exposure to low-dose ionizing radiation, even below the permitted levels,
      could result in increased oxidative stress, which may lead to DNA damage and
      mutagenicity.

PMID- 15998598
TI  - Supporting communication in health care.

PMID- 15998596
TI  - Chemokine receptor internalization and intracellular trafficking.
AB  - The internalization and intracellular trafficking of chemokine receptors have
      important implications for the cellular responses elicited by chemokine
      receptors. The major pathway by which chemokine receptors internalize is the
      clathrin-mediated pathway, but some receptors may utilize lipid rafts/caveolae
      dependent internalization routes. This review discusses the current knowledge and
      controversies regarding these two different routes of endocytosis. The functional
      consequences of internalization and the regulation of chemokine receptor
      recycling will also be addressed. Modifications of chemokine receptors, such as
      palmitoylation, ubiquitination, glycosylation, and sulfation, may also impact
      trafficking, chemotaxis and signaling. Finally, this review will cover the
      internalization and trafficking of viral and decoy chemokine receptors.

PMID- 15998599
TI  - The amount of hepatitis C viral RNA is correlated to the expression level of
      scavenger receptor class B type 1 in patients' livers.

PMID- 15998600
TI  - Identification of viral agents associated with diarrhea in young children during
      a winter season in Beijing, China.
AB  - BACKGROUND: Viral diarrhea remains a major cause of childhood morbidity and
      mortality worldwide. Although rotavirus was extensively studied in China, few
      comprehensive studies of all viral agents related to diarrhea in children have
      been conducted. OBJECTIVES: Our study was performed to investigate the role of
      enteric viruses in acute diarrhea in our country and to evaluate methods that
      could be used in routine diagnostics. STUDY DESIGN: One hundred stool samples
      were collected from children under 5 years of age seeking medical care for acute
      diarrhea during the winter season 2000/2001 in Beijing Children's Hospital. All
      specimens were initially screened microscopically for leucocytes/red blood cells.
      Samples with negative results were analyzed for virus presence using commercial
      EIAs and/or in-house RT-PCRs. RESULTS: At least one viral agent was found in 67%
      of the specimens. The frequency of rotavirus, astrovirus, norovirus and enteric
      adenovirus was 59%, 8%, 6% and 2%, respectively. Dual infections were found in
      9.0% (6/67) of the positive samples. The results from rotavirus and astrovirus
      EIAs were concordant with those of rotavirus and astrovirus RT-PCRs. CONCLUSIONS:
      Enteric viruses play an important role in pediatric diarrhea during the winter
      season in China. A combination of microscopic examination of stool samples with
      specific EIA assays to detect virus antigen in stool specimens may be suitable
      for routine diagnostics.

PMID- 15998601
TI  - Auditory brain-stem, middle- and long-latency evoked potentials in mild cognitive
      impairment.
AB  - OBJECTIVE: Mild cognitive impairment (MCI) is a selective episodic memory deficit
      in the elderly with a high risk of Alzheimer's disease. The amplitudes of a long
      latency auditory evoked potential (P50) are larger in MCI compared to age-matched
      controls. We tested whether increased P50 amplitudes in MCI were accompanied by
      changes of middle-latency potentials occurring around 50 ms and/or auditory brain
      stem potentials. METHODS: Auditory evoked potentials were recorded from age
      matched controls (n = 16) and MCI (n = 17) in a passive listening paradigm at two
      stimulus presentation rates (2/s, 1/1.5 s). A subset of subjects also received
      stimuli at a rate of 1/3 s. RESULTS: Relative to controls, MCI subjects had
      larger long-latency P50 amplitudes at all stimulus rates. Significant group
      differences in N100 amplitude were dependent on stimulus rate. Amplitudes of the
      middle-latency components (Pa, Nb, P1 peaking at approximately 30, 40, and 50 ms,
      respectively) did not differ between groups, but a slow wave between 30 and 49 ms
      on which the middle-latency components arose was significantly increased in MCI.
      ABR Wave V latency and amplitude did not differ significantly between groups.
      CONCLUSIONS: The increase of long-latency P50 amplitudes in MCI reflects changes
      of a middle-latency slow wave, but not of transient middle-latency components.
      There was no evidence of group difference at the brain-stem level. SIGNIFICANCE:
      Increased slow wave occurring as early as 50 ms may reflect neurophysiological
      consequences of neuropathology in MCI.

PMID- 15998602
TI  - Multifocal visual evoked potentials--a method study of responses from small
      sectors of the visual field.
AB  - OBJECTIVE: A method study of the mfVEP technique to establish a standardised way
      to identify stable response components from small areas in all parts of the
      visual field and a test-retest reliability study. METHODS: MfVEP was recorded
      from 26 healthy volunteers. RESULTS: Two response components could be clearly
      identified. The latencies corresponded to those of the traditional VEP response
      (N75 and P100). The visual field was divided into 12 sectors. A characteristic
      pattern was obtained. Component I was mainly negative in the upper sectors and
      positive in the lower sectors. Component II was positive in the upper sectors and
      negative in the lower ones. Most of the sectors with missing responses were the
      ones adjacent to the horizontal meridian, corresponding to the phase reversals.
      In a test-retest reliability study, the amplitude and latency measurements of the
      second test were plotted against those of the first test. Correlation
      coefficients between 0.84 and 0.93 were obtained. CONCLUSIONS: The mfVEP allows a
      reliable quantification of two response components from small parts of the visual
      field. SIGNIFICANCE: This paper suggests that mfVEP could be a valuable
      supplement to the traditional VEP for exploring restricted parts of the visual
      pathways.

PMID- 15998603
TI  - Detection of prenatal exposure to several classes of environmental toxicants and
      their metabolites by gas chromatography-mass spectrometry in maternal and
      umbilical cord blood.
AB  - We developed a sensitive method to detect several classes of pesticides and their
      metabolites in maternal and cord whole blood using electron-impact gas
      chromatography-mass spectrometry (GC-MS). The method can detect parent and
      metabolite compounds at levels of <0.10 and 0.20mug/mL, respectively, with high
      accuracy and recovery. Analysis of blood from mother-infant dyads from an area of
      high pesticide use in the Philippines showed detectable levels of propoxur, 3
      phenoxybenzoic acid (3-PBA), and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene
      (p,p'-DDE) in maternal and umbilical cord blood. GC-MS analysis of several
      classes of parent pesticides and their metabolites in maternal and cord blood
      provides a sensitive and specific method to detect pesticide exposure during
      pregnancy.

PMID- 15998604
TI  - Immobilization of lipase onto micron-size magnetic beads.
AB  - A novel and economical magnetic poly(methacrylate-divinylbenzene) microsphere
      (less than 8 microm in diameter) was synthesized by the modified suspension
      polymerization of methacrylate and cross-linker divinylbenzene in the presence of
      magnetic fluid. Then, surface aminolysis was employed to obtain a high content of
      surface amino groups (0.40-0.55 mmolg(-1) supports). The morphology and
      properties of these magnetic supports were characterized with scanning electron
      microscopy, transmission electron microscopy, Fourier transform infrared
      spectroscopy and a vibrating sample magnetometer. These magnetic supports
      exhibited superparamagnetism with a high specific saturation magnetization
      (sigma(s)) of 14.6 emicrog(-1). Candida cylindracea lipase was covalently
      immobilized on the amino-functionalized magnetic supports with the activity
      recovery up to 72.4% and enzyme loading of 34.0 mgg(-1) support, remarkably
      higher than the previous studies. The factors involved in the activity recovery
      and enzymatic properties of the immobilized lipase prepared were studied in
      comparison with free lipase, for which olive oil was chosen as the substrate. The
      results show that the immobilized lipase has good stability and reusability after
      recovery by magnetic separation within 20s.

PMID- 15998605
TI  - Microbes as trigger for primary biliary cirrhosis and primary sclerosing
      cholangitis.

PMID- 15998606
TI  - Privacy vs usability: a qualitative exploration of patients' experiences with
      secure Internet communication with their general practitioner.
AB  - BACKGROUND: Direct electronic communication between patients and physicians has
      the potential to empower patients and improve health care services. Communication
      by regular email is, however, considered a security threat in many countries and
      is not recommended. Systems which offer secure communication have now emerged.
      Unlike regular email, secure systems require that users authenticate themselves.
      However, the authentication steps per se may become barriers that reduce use.
      OBJECTIVES: The objective was to study the experiences of patients who were using
      a secure electronic communication system. The focus of the study was the users'
      privacy versus the usability of the system. METHODS: Qualitative interviews were
      conducted with 15 patients who used a secure communication system (MedAxess) to
      exchange personal health information with their primary care physician. RESULTS:
      Six main themes were identified from the interviews: (1) supporting simple
      questions, (2) security issues, (3) aspects of written communication, (4) trust
      in the physician, (5) simplicity of MedAxess, and (6) trouble using the system.
      By using the system, about half of the patients (8/15) experienced easier access
      to their physician, with whom they tended to solve minor health problems and
      elaborate on more complex illness experiences. Two thirds of the respondents
      (10/15) found that their physician quickly responded to their MedAxess requests.
      As a result of the security barriers, the users felt that the system was secure.
      However, due to the same barriers, the patients considered the log-in procedure
      cumbersome, which had considerable negative impact on the actual use of the
      system. CONCLUSIONS: Despite a perceived need for secure electronic patient
      physician communication systems, security barriers may diminish their overall
      usefulness. A dual approach is necessary to improve this situation: patients need
      to be better informed about security issues, and, at the same time, their
      experiences of using secure systems must be studied and used to improve user
      interfaces.

PMID- 15998607
TI  - Overcoming Depression on the Internet (ODIN) (2): a randomized trial of a self
      help depression skills program with reminders.
AB  - BACKGROUND: Guided self-help programs for depression (with associated therapist
      contact) have been successfully delivered over the Internet. However, previous
      trials of pure self-help Internet programs for depression (without therapist
      contact), including an earlier trial conducted by us, have failed to yield
      positive results. We hypothesized that methods to increase participant usage of
      the intervention, such as postcard or telephone reminders, might result in
      significant effects on depression. OBJECTIVES: This paper presents a second
      randomized trial of a pure self-help Internet site, ODIN (Overcoming Depression
      on the InterNet), for adults with self-reported depression. We hypothesized that
      frequently reminded participants receiving the Internet program would report
      greater reduction in depression symptoms and greater improvements in mental and
      physical health functioning than a comparison group with usual treatment and no
      access to ODIN. METHODS: This was a three-arm randomized control trial with a
      usual treatment control group and two ODIN intervention groups receiving
      reminders through postcards or brief telephone calls. The setting was a nonprofit
      health maintenance organization (HMO). We mailed recruitment brochures by US post
      to two groups: adults (n = 6030) who received depression medication or
      psychotherapy in the previous 30 days, and an age- and gender-matched group of
      adults (n = 6021) who did not receive such services. At enrollment and at 5-, 10-
      and 16-weeks follow-up, participants were reminded by email (and telephone, if
      nonresponsive) to complete online versions of the Center for Epidemiological
      Studies Depression Scale (CES-D) and the Short Form 12 (SF-12). We also recorded
      participant HMO health care services utilization in the 12 months following study
      enrollment. RESULTS: Out of a recruitment pool of 12051 approached subjects, 255
      persons accessed the Internet enrollment site, completed the online consent form,
      and were randomized to one of the three groups: (1) treatment as usual control
      group without access to the ODIN website (n = 100), (2) ODIN program group with
      postcard reminders (n = 75), and (3) ODIN program group with telephone reminders
      (n = 80). Across all groups, follow-up completion rates were 64% (n = 164) at 5
      weeks, 68% (n = 173) at 10 weeks, and 66% (n = 169) at 16 weeks. In an intention
      to-treat analysis, intervention participants reported greater reductions in
      depression compared to the control group (P = .03; effect size = 0.277 standard
      deviation units). A more pronounced effect was detected among participants who
      were more severely depressed at baseline (P = .02; effect size = 0.537 standard
      deviation units). By the end of the study, 20% more intervention participants
      moved from the disordered to normal range on the CES-D. We found no difference
      between the two intervention groups with different reminders in outcomes measures
      or in frequency of log-ons. We also found no significant intervention effects on
      the SF-12 or health care services. CONCLUSIONS: In contrast to our earlier trial,
      in which participants were not reminded to use ODIN, in this trial we found a
      positive effect of the ODIN intervention compared to the control group. Future
      studies should address limitations of this trial, including relatively low
      enrollment and follow-up completion rates, and a restricted number of outcome
      measures. However, the low incremental costs of delivering this Internet program
      makes it feasible to offer this type of program to large populations with
      widespread Internet access.

PMID- 15998608
TI  - Vaccine criticism on the World Wide Web.
AB  - BACKGROUND: The incidence of vaccine-preventable diseases is directly related to
      the number of unvaccinated children. Parents who refuse vaccination of their
      children frequently express concerns about vaccine safety. The Internet can
      influence perceptions about vaccines because it is the fastest growing source of
      consumer health information. However, few studies have analyzed vaccine criticism
      on the Web. OBJECTIVE: The purposes of this paper are to examine vaccine
      criticism on the Internet and to analyze the websites in order to identify common
      characteristics and ethical allegations. METHODS: A structured Web search was
      conducted for the terms "vaccine," "vaccination," "vaccinate," and "anti
      vaccination" using a metasearch program that incorporated 8 search engines. This
      yielded 1138 Web pages representing 750 sites. Two researchers reviewed the sites
      for inclusion/exclusion criteria, resulting in 78 vaccine-critical sites, which
      were then abstracted for design, content, and allegations. RESULTS: The most
      common characteristic of vaccine-critical websites was the inclusion of
      statements linking vaccinations with specific adverse reactions, especially
      idiopathic chronic diseases such as multiple sclerosis, autism, and diabetes.
      Other common attributes (> or = 70% of websites) were links to other vaccine
      critical websites; charges that vaccines contain contaminants, mercury, or "hot
      lots" that cause adverse events; claims that vaccines provide only temporary
      protection and that the diseases prevented are mild; appeals for responsible
      parenting through education and resisting the establishment; allegations of
      conspiracies and cover-ups to hide the truth about vaccine safety; and charges
      that civil liberties are violated through mandatory vaccination. CONCLUSIONS:
      Vaccine-critical websites frequently make serious allegations. With the
      burgeoning of the Internet as a health information source, an undiscerning or
      incompletely educated public may accept these claims and refuse vaccination of
      their children. As this occurs, the incidence of vaccine-preventable diseases can
      be expected to rise.

PMID- 15998609
TI  - A case study of a retracted systematic review on interactive health communication
      applications: impact on media, scientists, and patients.
AB  - BACKGROUND: In October 2004, a flawed systematic review entitled "Interactive
      Health Communication Applications for People with Chronic Disease" was published
      in the Cochrane Library, accompanied by several press releases in which authors
      warned the public of the negative health consequences of interactive health
      communication applications, including the Internet. Within days of the review's
      publication, scientists identified major coding errors and other methodological
      problems that invalidated the principal conclusions of the study and led to a
      retraction. While the original study results and their negative conclusions were
      widely publicized in the media, the retraction seemed to go unnoticed. OBJECTIVE:
      This paper aims to document an unprecedented case of misinformation from a
      Cochrane review and its impact on media, scientists, and patients. As well, it
      aims to identify the generic factors leading to the incident and suggest
      remedies. METHODS: This was a qualitative study of the events leading to the
      retraction of the publication and of the reactions from media, scientists, and
      patients. This includes a review and content analysis of academic and mass media
      articles responding to the publication and retraction. Mass media articles were
      retrieved in May 2005 from LexisNexis Academic and Google and were classified and
      tallied. The extended case method is employed, and the analysis is also applied
      to comparable publishing events. RESULTS: A search on LexisNexis Academic
      database with the query "Elizabeth Murray AND health" for the period of June 2004
      to May 2005 revealed a total of 15 press reports, of which only 1 addressed the
      retraction. Google was searched for references to the review, and the first 200
      retrieved hits were analyzed. Of these, 170 pages were not related to the review.
      Of the remaining 30 pages, 23 (77%) were reports about the original publication
      that did not mention the retraction, 1 (3%) was a bibliography not mentioning the
      retraction, and 6 (20%) addressed the retraction, of which only 1 was a non
      Cochrane-related source. CONCLUSIONS: Analyzed retrievals showed that the mass
      media gave more coverage to the Cochrane review than to the retraction or to a
      related systematic review with a similar scope but a different conclusion.
      Questionable results were prematurely disseminated, oversimplified, and
      sensationalized, while the retraction was hardly noticed by the public. Open
      commentary by scientists and patients helped to rapidly identify the errors but
      did not prevent or correct the dissemination of misinformation.

PMID- 15998610
TI  - Teaching elderly adults to use the Internet to access health care information:
      before-after study.
AB  - BACKGROUND: Much has been written about the Internet's potential to revolutionize
      health care delivery. As younger populations increasingly utilize Internet-based
      health care information, it will be essential to ensure that the elderly become
      adept at using this medium for health care purposes, especially those from
      minority, low income, and limited educational backgrounds. OBJECTIVE: This paper
      presents the results of a program designed to teach elderly adults to use the
      Internet to access health care information. The objective was to examine whether
      the training led to changes in participant's perceptions of their health,
      perceptions of their interactions with health care providers, health information
      seeking behaviors, and self-care activities. METHODS: Participants attended a 5
      week training course held in public libraries and senior community centers within
      the greater Pittsburgh and Allegheny County region. Classes within each seminar
      lasted 2 hours and consisted of lecture and hands-on training. Baseline surveys
      were administered prior to the course, 5-week follow-up surveys were administered
      immediately after the course, and final surveys were mailed 1 year later.
      Instruments included the Multidimensional Health Locus of Control (MHLC) Scale,
      which measures three domains of locus of control (internal, external, and
      chance); the Krantz Health Opinion Survey (HOS); and the Lau, Hartman, and Ware
      Health Value Survey. Two additional questionnaires included multiple choice and
      qualitative questions designed to measure participants' Internet utilization and
      levels of health care participation. The Health Participation Survey was
      administered with the baseline survey. The Internet Use Survey was administered
      at the 1-year mark and contained several items from the Health Participation
      Survey, which allowed comparison between baseline and 1-year responses. RESULTS:
      Of the60 elderly adults who began the training course, 42 (mean age 72) completed
      the entire 5-week training program and the 5-week follow-up questionnaire
      administered immediately after the program, and 27 completed the 1-year follow-up
      survey. Statistically significant differences were found between baseline and 5
      week follow-up results for MHLC chance subscores in males (P = .02) and females
      (P = .05), as well as total HOS information seeking scores (P = .05). However,
      these statistically significant findings disappeared when all 60 original
      participants were included using a "last observation carried forward" imputation.
      No statistically significant changes were found between baseline and 5-week
      follow-up surveys for MHLC external (P = .44) and internal (P = .97) locus of
      control scores in both genders, or for the HOS behavioral involvement subscale (P
      = .65). CONCLUSIONS: We failed to show robust before-after effects for most of
      the outcomes measured. Elderly adults may be willing to use the Internet as a
      source for general health information; however, when making decisions about their
      health care, our participants seemed to adhere to a physician-centered model of
      care. Demographic and situational variables may play a large role in determining
      which seniors will use the Internet for making behavioral decisions about their
      health care and in which scenarios they will do so.

PMID- 15998611
TI  - Information needs and visitors' experience of an Internet expert forum on
      infertility.
AB  - BACKGROUND: Patients increasingly use health portals and Web-based expert forums
      (ask-the-doctor services), but little is known about the specific needs of
      Internet users visiting such websites, the nature of their requests, or how
      satisfied they are with Internet health experts. OBJECTIVE: The aim of this study
      was to analyze the information requests of (mostly female) patients visiting an
      Internet expert forum on involuntary childlessness and their satisfaction with
      the experts' feedback. METHODS: We posted an electronic questionnaire on a
      website hosting an expert forum on involuntary childlessness. The questionnaire
      was "activated" whenever a visitor sent a question or request to the expert
      forum. The survey focused on the reasons for visiting the expert forum and
      whether the visitors were satisfied with the experts' answers to previously
      posted questions. The free-text questions of visitors who answered the survey
      were analyzed using Atlas-ti, a software program for qualitative data analysis.
      RESULTS: Over a period of 6 months, 513 out of 610 visitors (84%) answered the
      questionnaire. The majority of respondents (65.5%) expected general information
      about involuntary childlessness, conception, or an evaluation of drugs. Others
      were concerned about their actual treatment (40.6%) and therapeutic options
      (28.8%). Out of 225 respondents who had previously contacted the forum, 223 has
      received an answer, and 123 (55.2%) were satisfied with the experts' answers.
      About half (105/223) of those users who had previously received an answer from
      the expert forum stated that they had discussed it with their own doctor. More of
      these users were satisfied with their subsequent care in fertility clinics than
      users who did not talk to their doctor about their Internet activities (93.9% vs
      76.1%; P = .015). According to the qualitative analysis, many requests (n = 194)
      were more or less trivial, especially those for information on basic aspects of
      reproduction. More than one-third of visitors (n = 199) sent detailed results of
      diagnostic tests and asked for a first or second opinion. Requests to the expert
      forum were also sent in order to obtain emotional support (17%) or to complain
      about a doctor (15%). CONCLUSIONS: Visitors who sent their laboratory findings to
      receive a thorough evaluation or a second opinion had a good command of the
      opportunities that an expert forum offers. One important expectation of the forum
      was emotional support, indicating psychological needs that were not met by
      medical providers. Future websites must find a compromise in order to protect
      experts from being overwhelmed by general, nonspecific requests while supporting
      patients with individualized answers.

PMID- 15998612
TI  - "Is Cybermedicine Killing You?"--The story of a Cochrane disaster.
AB  - This editorial briefly reviews the series of unfortunate events that led to the
      publication, dissemination, and eventual retraction of a flawed Cochrane
      systematic review on interactive health communication applications (IHCAs), which
      was widely reported in the media with headlines such as "Internet Makes Us Sick,"
      "Knowledge May Be Hazardous to Web Consumers' Health," "Too Much Advice Can Be
      Bad for Your Health," "Click to Get Sick?," and even "Is Cybermedicine Killing
      You?". While the media attention helped to speed up the identification of errors,
      leading to a retraction of the review after only 13 days, a paper published in
      this issue of JMIR by Rada shows that the retraction, in contrast to the original
      review, remained largely unnoticed by the public. We discuss the three flaws of
      the review, which include (1) data extraction and coding errors, (2) the pooling
      of heterogeneous studies, and (3) a problematic and ambiguous scope and,
      possibly, some overlooked studies. We then discuss "retraction ethics" for
      researchers, editors/publishers, and journalists. Researchers and editors should,
      in the case of retractions, match the aggressiveness of the original
      dissemination campaign if errors are detected. It is argued that researchers and
      their organizations may have an ethical obligation to track down journalists who
      reported stories on the basis of a flawed study and to specifically ask them to
      publish an article indicating the error. Journalists should respond to errors or
      retractions with reports that have the same prominence as the original story.
      Finally, we look at some of the lessons for the Cochrane Collaboration, which
      include (1) improving the peer-review system by routinely sending out pre-prints
      to authors of the original studies, (2) avoiding downplay of the magnitude of
      errors if they occur, (3) addressing the usability issues of RevMan, and (4)
      making critical articles such as retraction notices open access.

PMID- 15998613
TI  - Cancer patients' self-reported attitudes about the Internet.
AB  - BACKGROUND: Increasing numbers of cancer patients are using the Internet, but
      little is known about their attitudes toward online health care. OBJECTIVE: The
      purpose of this substudy was to analyze cancer patients' attitudes toward online
      health care. METHODS: This was a substudy of 41 persons with cancer who used the
      Internet for health care information and support and who completed the Attitudes
      Toward Online Health Care (ATOHC) survey. RESULTS: The majority of study
      participants were married, held graduate degrees, and had high incomes. Using a
      five-point Likert scale, means for the five dimensions of the ATOHC survey were
      as follows: community and news 3.22 (SD = 1.01), outcomes 3.20 (SD = 1.08),
      trusted information and advice 2.73 (SD = 0.66), self-efficacy in evaluating
      information and intention 3.46 (SD = 0.65), and disclosure 3.15 (SD = 1.06). The
      average response fell between "About half the time" and "Usually." Favorite
      websites for content were Medscape and WebMD, while favorite sites for support
      were WebMD and Mediconsult. CONCLUSIONS: Respondents were generally eager to
      obtain and offer cancer information and support online, but they were skeptical
      of unknown sources. They were comfortable both giving and receiving information
      and support. Respondents were interested in the experiences of other patients and
      benefited by their direct and indirect interactions with them. Respondents felt
      that they coped better with their illness and experienced less uncertainty and
      anxiety as a result of their online experiences. They reported a certain level of
      trust, primarily for established reputable sources of information, and they were
      confident in their ability to evaluate the information, including research
      reports. In addition, cancer patients displayed a healthy skepticism when
      presented with the option of divulging their personal health information;
      however, they were willing to provide personal details if, as a result, a website
      provided them with individualized information.

PMID- 15998614
TI  - An ecological framework for cancer communication: implications for research.
AB  - The field of cancer communication has undergone a major revolution as a result of
      the Internet. As recently as the early 1990s, face-to-face, print, and the
      telephone were the dominant methods of communication between health professionals
      and individuals in support of the prevention and treatment of cancer. Computer
      supported interactive media existed, but this usually required sophisticated
      computer and video platforms that limited availability. The introduction of point
      and-click interfaces for the Internet dramatically improved the ability of non
      expert computer users to obtain and publish information electronically on the
      Web. Demand for Web access has driven computer sales for the home setting and
      improved the availability, capability, and affordability of desktop computers.
      New advances in information and computing technologies will lead to similarly
      dramatic changes in the affordability and accessibility of computers. Computers
      will move from the desktop into the environment and onto the body. Computers are
      becoming smaller, faster, more sophisticated, more responsive, less expensive,
      and--essentially--ubiquitous. Computers are evolving into much more than desktop
      communication devices. New computers include sensing, monitoring, geospatial
      tracking, just-in-time knowledge presentation, and a host of other information
      processes. The challenge for cancer communication researchers is to acknowledge
      the expanded capability of the Web and to move beyond the approaches to health
      promotion, behavior change, and communication that emerged during an era when
      language- and image-based interpersonal and mass communication strategies
      predominated. Ecological theory has been advanced since the early 1900s to
      explain the highly complex relationships among individuals, society,
      organizations, the built and natural environments, and personal and population
      health and well-being. This paper provides background on ecological theory,
      advances an Ecological Model of Internet-Based Cancer Communication intended to
      broaden the vision of potential uses of the Internet for cancer communication,
      and provides some examples of how such a model might inform future research and
      development in cancer communication.

PMID- 15998615
TI  - An Internet-based cancer clinical trials matching resource.
AB  - BACKGROUND: Many patients are now accessing the Internet to obtain cancer
      clinical trials information. However, services offering clinical trials
      recruitment information have not been well defined. OBJECTIVES: This study
      describes one of the first Web-based cancer clinical trials matching resources
      and the demographics of users who were successfully matched. METHODS: OncoLink is
      the Internet-based educational resource managed by the University of Pennsylvania
      Cancer Center (UPCC) and serves between 1 and 2 million pages per month to over
      385000 unique IP addresses. OncoLink launched one of the first clinical trials
      matching resources on the Internet that allowed patients to enter demographic
      data through a secure connection and be matched to clinical trials. For patients
      with matches to potential trials, appointments were facilitated with the
      principal investigators. RESULTS: While we did not keep track of patients who
      could not be matched, 627 patients who submitted online applications between
      January 2002 and April 2003 were successfully matched for potential enrollment in
      clinical trials. The mean age of the patient population was 56 years (range 18-88
      years). Males represented 60% of the patient population, and over 90% of users
      were Caucasian. Most of the applications were from patients with colorectal
      cancer (13%), lung cancer (14%), melanoma (10%), and non-Hodgkin's lymphoma (9%).
      CONCLUSIONS: This report shows that a significant number of patients are willing
      to use the Internet for enrolling in clinical trials. Care must be taken to reach
      patients from a variety of socioeconomic and racial backgrounds. This Internet
      resource helps to facilitate a consultation with a cancer patient who is
      prescreened and motivated to enroll in clinical trials.

PMID- 15998616
TI  - The role of user input in shaping online information from the National Cancer
      Institute.
AB  - The National Cancer Institute (NCI) was among the first federal agencies to
      recognize the potential of the Internet for disseminating health-related
      information. The evolution and refinement of NCI's online cancer information has
      been substantially "user driven"-from the launch of CancerNet in 1995 to the
      recent redesign of its award-winning successor, the NCI website. This article
      presents an overview of NCI's multi-pronged approach to gathering input about its
      online information products, including stakeholder meetings, focus groups,
      standard and customized online user surveys, usability testing, heuristic
      reviews, and search log analysis. Also highlighted are some of the many
      enhancements that have been made to NCI's online cancer information products
      based on user input.

PMID- 15998618
TI  - Online health behavior and disease management programs: are we ready for them?
      Are they ready for us?
AB  - Advancing the science and practice of health promotion and disease management on
      the Internet requires a systematic program of research examining the population
      impact of such programs. With impact described as the combination of
      effectiveness and participation, such research needs to include the examination
      of the quality and effectiveness of programs that are available to the general
      public, as well as descriptive and predictive knowledge about population
      readiness to participate in such programs. There have been few studies examining
      the quality of interactive health behavior change (HBC) programs on the Internet,
      and even fewer investigations of the effectiveness of such programs. Based on the
      review of over 300 HBC programs on the Internet using the "5 A's" of Health
      Behavior Change on the Internet (HBC-I Screener), which represent standard
      minimum guidelines for evaluation, it appears HBC on the Internet is in the early
      stages of development. As health behavior change on the Internet matures from the
      provision of health information to meeting the requirements necessary to produce
      health behavior change, and as program developers take advantage of the
      interactive nature of the Internet, the basic screening and expanded evaluation
      criteria developed in this project will provide templates for both consumers and
      developers of programs. The second component necessary for evaluating the impact
      of HBC on the Internet is the extent to which the population is ready to
      participate in such programs. We need to move beyond a narrow focus on early
      adopters and produce a population perspective that includes those not ready,
      those getting ready, and those ready to use such programs, as well as those
      already participating. By understanding participation levels of such programs,
      and what drives this participation, the development and dissemination of
      practical tailored and targeted interventions can help maximize population
      participation in Internet programs for health behavior change.

PMID- 15998617
TI  - Reducing the cancer burden of lifestyle factors: opportunities and challenges of
      the Internet.
AB  - This paper focuses on the Internet as a tool for enhancing behavior and lifestyle
      changes to reduce the burden of cancer at a population level. The premise of this
      paper is that the Internet can and should be leveraged to bridge the chasm
      between basic science, clinical trials, and public health. Our focus is
      specifically on the opportunity to disseminate effective behavioral science
      interventions via the Internet in order to decrease the prevalence of behavioral
      risk factors for cancer. The examples herein are primarily drawn from tobacco use
      to illustrate issues that can be applied more generally to other behavioral risk
      factors for cancer. Four areas will be addressed: (1) the scientific basis and
      rationale for delivering lifestyle behavior change interventions via the
      Internet; (2) the need to determine the quality of Internet interventions; (3)
      methodological considerations in conducting evaluations of Internet
      interventions; and (4) recommendations for a transdisciplinary approach to
      Internet intervention development and evaluation.

PMID- 15998619
TI  - Utility of two cancer organization websites for a multiethnic, public hospital
      oncology population: comparative cross-sectional survey.
AB  - BACKGROUND: While information websites have been developed by major cancer
      organizations, their appropriateness for patients in multiethnic, multilingual
      public hospital settings has received limited attention. OBJECTIVE: The objective
      of the study was to determine the utility of cancer information websites for a
      public hospital patient population. METHODS: A 70-item questionnaire was
      developed to evaluate cancer information seeking behavior, Internet access and
      use, and content appropriateness of two cancer information websites: People
      Living with Cancer from the American Society of Clinical Oncology (ASCO) and
      Breast Cancer Info from the Susan Komen Breast Cancer Foundation (SKF).
      Interviews were conducted with consecutive consenting oncology patients seen in a
      public hospital oncology clinic. RESULTS: Fifty-nine persons participated in the
      survey. The response rate was 80%. Participants were Caucasian (25%), African
      American (19%), Hispanic (42%), and Asian/Pacific Islander (11%). English was the
      primary language in 53% of participants, 56% had a high school education or less,
      and 74% had an annual income less than US 35000 dollars. With respect to computer
      and Internet use, 71% had computer access, and 44% searched for cancer
      information online, with more being interested in obtaining online information in
      the future (63%). Participants who had computer access were likely to be English
      speaking (P = .04). Those less likely to have previously used a computer tended
      to have a lower annual income (P = .02) or to be males aged 55 years or older (P
      < .05). When shown sample content from the two websites, almost all participants
      stated that it was "easy to understand" (ASCO 96%, SKF 96%) and had "easy to
      understand terms" (ASCO 94%, SKF 92%). Somewhat fewer respondents agreed that the
      websites provided "information they could use" (ASCO 88%, SKF 80%) or that they
      would return to these websites (ASCO 73%, SKF 68%). The majority planned to
      "discuss website information with their oncologists" (ASCO 82%, SKF 70%).
      CONCLUSIONS: Multiethnic, multilingual cancer patients at a public county
      hospital commonly had Internet access and found the content of two websites
      representative of major cancer organizations to be both understandable and
      useful.

PMID- 15998620
TI  - The need for online information on the economic consequences of cancer diagnosis,
      treatment, and survivorship.
AB  - The Internet is commonly used to provide treatment information to patients
      diagnosed with cancer. Notably missing from the existing websites is information
      on the cost of cancer care in terms of medical costs to the patient and work
      related consequences. The purpose of this paper is to describe what is known
      about the economic cost of cancer and to describe how this information can be
      structured so that it is of more benefit to patients. This paper first provides
      an overview of the information available regarding medical expenses and
      productivity costs associated with cancer survivorship, particularly with respect
      to cancer and employment. Second, it draws attention to the sparse economic
      information available online to cancer survivors. Patients can find information
      on sources of financial assistance, but they cannot estimate from the available
      information the cost of their care or anticipate the impact that cancer and its
      treatment may have on their jobs. Finally, a strategy for filling the void in
      online economic cancer information is described. Substantial opportunity exists
      to provide economic information to cancer patients and their families. The
      Internet is a natural forum for gathering and disseminating economic information.
      A unique advantage of the Internet is its ability to put information immediately
      in the hands of cancer patients and their families--assisting them to become
      informed consumers and skilled negotiators.

PMID- 15998621
TI  - Emerging technologies for cancer prevention and other population health
      challenges.
AB  - Emerging technologies, such as information and communication technologies
      (including future versions of the Internet), microelectromechanical systems,
      nanotechnologies, genomics, robotics, artificial intelligence, and sensors,
      provide enormous opportunities for enhancing health and quality of life.
      Population health technologies (PHTs) encompass the various applications of
      emerging technologies to improve the health of populations and communities. These
      technologies may change many population health paradigms, including those related
      to cancer prevention and control. In the future, emerging technologies will allow
      true customization of health communication to individuals, and existing tailoring
      approaches will be considered very crude. Environmental monitoring systems based
      on emerging technologies could also provide real-time information that health
      officials and community residents could use immediately to ameliorate potential
      carcinogenic or unhealthy exposures. Accelerating the application and diffusion
      of emerging technologies to population health challenges will require a
      multipronged approach, including new transdisciplinary programs, increased
      funding, supportive infrastructure, and policy changes.

PMID- 15998622
TI  - Use of Internet audience measurement data to gauge market share for online health
      information services.
AB  - BACKGROUND: The transition to a largely Internet and Web-based environment for
      dissemination of health information has changed the health information landscape
      and the framework for evaluation of such activities. A multidimensional
      evaluative approach is needed. OBJECTIVE: This paper discusses one important
      dimension of Web evaluation-usage data. In particular, we discuss the collection
      and analysis of external data on website usage in order to develop a better
      understanding of the health information (and related US government information)
      market space, and to estimate the market share or relative levels of usage for
      National Library of Medicine (NLM) and National Institutes of Health (NIH)
      websites compared to other health information providers. METHODS: The primary
      method presented is Internet audience measurement based on Web usage by external
      panels of users and assembled by private vendors-in this case, comScore. A
      secondary method discussed is Web usage based on Web log software data. The
      principle metrics for both methods are unique visitors and total pages downloaded
      per month. RESULTS: NLM websites (primarily MedlinePlus and PubMed) account for
      55% to 80% of total NIH website usage depending on the metric used. In turn,
      NIH.gov top-level domain usage (inclusive of NLM) ranks second only behind WebMD
      in the US domestic home health information market and ranks first on a global
      basis. NIH.gov consistently ranks among the top three or four US government top
      level domains based on global Web usage. On a site-specific basis, the top health
      information websites in terms of global usage appear to be WebMD, MSN Health,
      PubMed, Yahoo! Health, AOL Health, and MedlinePlus. Based on MedlinePlus Web log
      data and external Internet audience measurement data, the three most heavily used
      cancer-centric websites appear to be www.cancer.gov (National Cancer Institute),
      www.cancer.org (American Cancer Society), and www.breastcancer.org (non-profit
      organization). CONCLUSIONS: Internet audience measurement has proven useful to
      NLM, with significant advantages compared to sole reliance on usage data from Web
      log software. Internet audience data has helped NLM better understand the
      relative usage of NLM and NIH websites in the intersection of the health
      information and US government information market sectors, which is the primary
      market intersector for NLM and NIH. However important, Web usage is only one
      dimension of a complete Web evaluation framework, and other primary research
      methods, such as online user surveys, usability tests, and focus groups, are also
      important for comprehensive evaluation that includes qualitative elements, such
      as user satisfaction and user friendliness, as well as quantitative indicators of
      website usage.

PMID- 15998623
TI  - How new subscribers use cancer-related online mailing lists.
AB  - BACKGROUND: Online cancer-related support is an under-studied resource that may
      serve an important function in the information seeking, care, and support of
      cancer patients and their families. With over 9.8 million cancer survivors
      (defined as anyone living with cancer) in the United States alone and the number
      growing worldwide, it is important to understand how they seek and use online
      resources to obtain the information they need, when they need it, and in a form
      and manner appropriate to them. These are stated cancer communication goals of
      the US National Cancer Institute. OBJECTIVES: Our purposes are to (1) present
      background information about online mailing lists and electronic support groups,
      (2) describe the rationale and methodology for the Health eCommunities (HeC)
      study, and (3) present preliminary baseline data on new subscribers to cancer
      related mailing lists. In particular, we describe subscribers' use of mailing
      lists, their reasons for using them, and their reactions to participating shortly
      after joining the lists. METHODS: From April to August 2004, we invited all new
      subscribers to 10 Association of Cancer Online Resources mailing lists to
      complete Web-based surveys. We analyzed baseline data from the respondents to
      examine their perceptions about cancer-related mailing lists and to describe how
      cancer patients and survivors used these lists in the period shortly after
      joining them. RESULTS: Cumulative email invitations were sent to 1368 new mailing
      list subscribers; 293 Web surveys were completed within the allotted time frame
      (21.4% response rate). Most respondents were over age 50 (n = 203, 72%), white (n
      = 286, 98%), college graduates (n = 161, 55%), and had health insurance (n = 283,
      97%). About 41% (n = 116) of new subscribers reported spending 1 to 3 hours per
      day reading and responding to list messages. They used the mailing lists for
      several reasons. Among the most frequently reported, 62% (n = 179) strongly
      agreed they used mailing lists to obtain information on how to deal with cancer,
      42% (n = 121) strongly agreed they used mailing lists for support, and 37% (n =
      109) strongly agreed that they were on the mailing lists to help others. Smaller
      proportions of new subscribers strongly agreed that others on the mailing lists
      had similar cancer experiences (n = 23, 9%), that they could relate to the
      experiences of others on the lists (n = 66, 27%), and that others on the list
      gave them good ideas about how to cope with cancer (n = 66, 27%). CONCLUSIONS:
      Cancer-related online mailing lists appear to be an important resource,
      especially for information seeking but also for support of cancer survivors.
      These were the primary motivators most members reported for joining mailing
      lists. The modest proportion of subscribers who strongly agreed that they could
      relate to others' cancer experiences (as well as similar responses to other
      process questions) is undoubtedly due at least in part to the short duration that
      these subscribers were involved with the mailing lists. Emerging data, including
      our own, suggest that mailing lists are perhaps under-used by minority
      patients/survivors. These preliminary data add to a growing body of research on
      health-related online communities, of which online mailing lists are one variant.

PMID- 15998624
TI  - Attributes of interactive online health information systems.
AB  - The development of online communication systems related to prevention, decision
      making, and coping with cancer has outpaced theoretical attention to the
      attributes that appeal to system users and that create effective interactions.
      This essay reviews a number of sociotechnical attributes related to online
      discussion systems and tutorials, including interactivity, presence, homophily,
      social distance, anonymity/privacy, and interaction management. These attributes
      are derived from different theoretical perspectives which have led to clinical
      trials and other empirical studies demonstrating effectiveness or attraction to
      end users. The effects of a subset of these attributes are connected to learning,
      social influence, and coping, as illustrated in evaluations of an interactive
      smoking prevention site and a cancer advice/support discussion system.

PMID- 15998626
TI  - Online cancer services: types of services offered and associated health outcomes.
AB  - There are advantages and disadvantages associated with utilization of online
      health services among individuals living with cancer. Accessing accurate,
      reliable health-related information online gives patients the power to enhance
      their understanding of information they obtain from their health care providers.
      However, online health information can often be confusing for patients to
      interpret, and it can sometimes be conflicting or incorrect. Based on a framework
      by Eysenbach, the following paper discusses various types of cancer services that
      are available online, and it addresses both positive and negative health outcomes
      that have been linked to utilizing such services.

PMID- 15998625
TI  - Creating a framework for online cancer services research to facilitate timely and
      interdisciplinary applications.
AB  - Researchers from a wide array of disciplines have conducted engaging and
      informative studies in recent years concerning the use of the Internet for cancer
      related services. Typically, these publications provide key data related to
      utilization statistics, how online information can be used, what users want or
      expect from the Internet, outcomes or impacts, and quality and credibility of
      websites. These are important themes for understanding online cancer issues.
      However, this special issue of the Journal of Medical Internet Research seeks to
      recast these themes in a way that will facilitate pragmatic and applied means of
      employing data in prescriptive and interdisciplinary ways. This issue includes 14
      papers that exemplify applications for the research framework recommended in this
      paper. This framework includes an expanded focus on the development and design of
      online cancer services, online consumer behavior/communication, behavior change,
      and living with cancer.

PMID- 15998627
TI  - Cancer Internet search activity on a major search engine, United States 2001
      2003.
AB  - BACKGROUND: To locate online health information, Internet users typically use a
      search engine, such as Yahoo! or Google. We studied Yahoo! search activity
      related to the 23 most common cancers in the United States. OBJECTIVE: The
      objective was to test three potential correlates of Yahoo! cancer search activity
      -estimated cancer incidence, estimated cancer mortality, and the volume of cancer
      news coverage--and to study the periodicity of and peaks in Yahoo! cancer search
      activity. METHODS: Yahoo! cancer search activity was obtained from a proprietary
      database called the Yahoo! Buzz Index. The American Cancer Society's estimates of
      cancer incidence and mortality were used. News reports associated with specific
      cancer types were identified using the LexisNexis "US News" database, which
      includes more than 400 national and regional newspapers and a variety of newswire
      services. RESULTS: The Yahoo! search activity associated with specific cancers
      correlated with their estimated incidence (Spearman rank correlation, rho = 0.50,
      P = .015), estimated mortality (rho = 0.66, P = .001), and volume of related news
      coverage (rho = 0.88, P < .001). Yahoo! cancer search activity tended to be
      higher on weekdays and during national cancer awareness months but lower during
      summer months; cancer news coverage also tended to follow these trends. Sharp
      increases in Yahoo! search activity scores from one day to the next appeared to
      be associated with increases in relevant news coverage. CONCLUSIONS: Media
      coverage appears to play a powerful role in prompting online searches for cancer
      information. Internet search activity offers an innovative tool for passive
      surveillance of health information-seeking behavior.

PMID- 15998628
TI  - Differential effects of dietary saturated and trans-fatty acids on expression of
      genes associated with insulin sensitivity in rat adipose tissue.
AB  - OBJECTIVE: Trans-fatty acids (TFAs) are formed during partial hydrogenation of
      vegetable oils and are shown to be more atherogenic than saturated fatty acids
      (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue
      insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that
      the effects of these fatty acids on insulin sensitivity could be mediated through
      an alteration in gene expression. In the current study we have investigated the
      effects of dietary TFAs or SFAs on expression of genes associated with insulin
      sensitivity in rat adipose tissue. DESIGN AND METHODS: Male weanling Wistar/NIN
      rats were divided into four groups and fed one of the following diets containing
      10% fat (g/100 g diet) differing only in the fatty acid composition for 3 months:
      control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA +
      1% LA) and TFA diet 2 (1.5% TFA + 2% LA). The mRNA expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma), lipoprotein lipase (LPL),
      glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in
      epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA
      to understand the beneficial effects of LA over the effects of TFA. RESULTS: Both
      dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA
      downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated
      PPARgamma and LPL. The effects of dietary TFA on PPARgamma and resistin were not
      counteracted by increased LA (TFA diet 2). CONCLUSION: The effects of SFAs on the
      aforementioned genes except PPARgamma could be extrapolated towards decreased
      insulin sensitivity, while only the alteration in the mRNA levels of PPARgamma
      and resistin could be associated with insulin resistance in TFA-fed rats. These
      findings suggest that dietary SFAs and TFAs alter the expression of different
      genes associated with insulin sensitivity in adipose tissue.

PMID- 15998631
TI  - The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid
      arthritis: increased susceptibility and severity in male patients (the Swedish
      TIRA project).
AB  - OBJECTIVES: To evaluate the influence of Fcgamma receptor IIIA (FcgammaRIIIA)
      158V/F polymorphism on susceptibility and disease severity in early rheumatoid
      arthritis (RA). METHODS: In 181 Swedish patients (128 women, 53 men) with RA of
      recent onset, disease and disability variables such as erythrocyte sedimentation
      rate, 28-joint disease activity score (DAS28) and health assessment questionnaire
      (HAQ) scores were monitored regularly during 3 yr. Three hundred and sixty-two
      controls were recruited from the same geographical area as the patients.
      FcgammaRIIIA genotyping was performed using denaturing high-performance liquid
      chromatography. RESULTS: In all RA patients, FcgammaRIIIA-158VV was significantly
      over-represented compared with controls [odds ratio (OR) 1.9, 95% confidence
      interval (CI) 1.01-3.5, P<0.05]. After stratifying for sex, the difference
      remained in the male population (OR 3.2, 95%CI 1.03-11, P<0.05) but disappeared
      among women (OR 1.4, 95%CI 0.7-3.1, P=0.4). In addition, 158VV patients were more
      likely to exhibit early joint erosions (OR 6.1, 95%CI 1.4-28, P<0.01). At
      baseline, patients with different FcgammaRIIIA genotypes did not differ with
      respect to measures of disease activity or functional ability. Thereafter, in
      male patients with at least one V allele the mean DAS28 and HAQ scores were
      higher compared with 158FF. In contrast, female patients with at least one 158V
      allele displayed lower mean DAS28 and HAQ scores compared with those with 158FF.
      CONCLUSIONS: In a male population, the FcgammaRIIIA-158VV genotype is associated
      with an increased risk of developing RA, and the 158V allele with more severe
      disease in early RA.

PMID- 15998632
TI  - PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish
      population.
AB  - OBJECTIVES: The presence of anti-citrullinated peptide antibodies is the most
      specific serological marker known of rheumatoid arthritis (RA). The PADI4 gene,
      encoding a haematopoietic isoform of the peptidylarginine deiminase
      citrullinating enzyme, has recently been associated with susceptibility to RA in
      the Japanese population. A subsequent UK report could not confirm this
      association, and a later French study also yielded a negative result. Given this
      discrepancy and the importance of antibodies against citrullinated peptides in
      the early course of the disease, we performed a replication study. METHODS: Three
      hundred and fifty-four Spanish RA patients and 498 Spanish controls were
      recruited from two Madrid hospitals. The padi4_104 and padi4_94 single-nucleotide
      polymorphisms (SNP) were analysed by TaqMan assays. RESULTS: Similarly to what
      was described in the British and French population, the less frequent allele of
      this SNP was not associated with the disease (genotype TT, 16.1% in RA patients
      vs 14.3% in controls; P = 0.46, odds ratio 1.15, 95% confidence interval 0.78
      1.71). A confirmatory negative result was obtained on analysing another SNP in
      the same gene, padi4_94, in 248 RA patients and 394 controls. CONCLUSIONS: The
      results of our group and from the British and French studies strongly suggest
      that polymorphisms of the PADI4 gene do not play a role in susceptibility to RA
      in European populations.

PMID- 15998629
TI  - Genetic analysis as a tool to investigate the molecular mechanisms underlying
      seed development in maize.
AB  - BACKGROUND: In angiosperms the seed is the outcome of double fertilization, a
      process leading to the formation of the embryo and the endosperm. The development
      of the two seed compartments goes through three main phases: polarization,
      differentiation of the main tissues and organs and maturation. SCOPE: This review
      focuses on the maize kernel as a model system for developmental and genetic
      studies of seed development in angiosperms. An overview of what is known about
      the genetic and molecular aspects underlying embryo and endosperm formation and
      maturation is presented. The role played by embryonic meristems in laying down
      the plant architecture is discussed. The acquisition of the different endosperm
      domains are presented together with the use of molecular markers available for
      the detection of these domains. Finally the role of programmed cell death in
      embryo and endosperm development is considered. CONCLUSIONS: The sequence of
      events occurring in the developing maize seed appears to be strictly regulated.
      Proper seed development requires the co-ordinated expression of embryo and
      endosperm genes and relies on the interaction between the two seed components and
      between the seed and the maternal tissues. Mutant analysis is instrumental in
      unravelling the genetic control underlying the formation of each compartment as
      well as the molecular signals interplaying between the two compartments.

PMID- 15998633
TI  - The relationship between hand paraesthesia and occupational factors: results from
      a population study.
AB  - OBJECTIVES: To investigate the association of occupational factors, both physical
      and psychosocial, with hand paraesthesia, and whether any such associations
      differ according to the concurrent presence of neck and upper limb pain (NULP).
      METHODS: A questionnaire was mailed to an age-stratified random sample of 9596
      adults. All subjects were asked about hand paraesthesia in the past 4 weeks.
      Information was obtained on respondents' main job (the job held for the longest
      time), whether this job involved any of six neck or upper limb activities on most
      or all days of the working week, and questions on the psychosocial aspects of the
      work environment. The questionnaire also asked about NULP according to a
      preshaded manikin. RESULTS: A total of 5133 people replied to the survey
      (adjusted response 53.5%). Of these, 1592 reported abnormal feelings in the hands
      (prevalence of 31.9%). Prolonged gripping, prolonged bending of the neck
      forwards, working with arms at/above shoulder height, low job control, many
      changes in tasks and low job support were independently associated with hand
      paraesthesia. Among responders also reporting NULP, working with arms at/above
      shoulder height and many changes in tasks were independently associated with hand
      paraesthesia; prolonged gripping was linked to hand paraesthesia in the absence
      of NULP. CONCLUSIONS: Hand paraesthesia is associated with physical and
      psychosocial workplace factors, although different work-related factors were
      associated with hand paraesthesia according to the concurrent presence of NULP,
      suggesting that these symptoms may not always be mediated in the same way.

PMID- 15998634
TI  - Deflazacort modulates the fibrinolytic pattern and reduces uPA-dependent
      chemioinvasion and proliferation in rheumatoid arthritis synoviocytes.
AB  - OBJECTIVE: Extracellular fibrinolysis, controlled by the cell-associated
      fibrinolytic system (urokinase plasminogen activator, uPA; uPA receptor, uPAR;
      plasminogen activator inhibitor type-1, PAI-1), is involved in cartilage damage
      generation and in rheumatoid arthritis (RA) synovitis. Since steroids reduce the
      rate of radiological progression of RA, we planned to evaluate in healthy and RA
      synoviocytes the effects of the steroid deflazacort on uPA, uPAR and PAI-1
      expression, and subsequent phenotypic modifications in terms of uPA/uPAR
      dependent invasion and proliferation. METHODS: uPA, uPAR and PAI-1 levels were
      studied by ELISA, RT-PCR (uPAR) and zymography (uPA) in synoviocytes from four RA
      patients and four healthy controls. Chemoinvasion was assessed by the Boyden
      chamber invasion assay, using Matrigel as the invasion substrate. Proliferation
      was evaluated by cell counting. Both invasion and proliferation were measured
      upon treatment with deflazacort 5 muM with or without parallel stimulation with
      uPA 500 ng/ml or in the presence of monoclonal anti-uPA and anti-uPAR antibodies.
      RESULTS: Invasion and proliferation of RA synoviocytes require a proper
      functional balance of the fibrinolytic system. Both deflazacort and monoclonal
      antibodies against uPA and uPAR reduced expression and activity of the system,
      thus inhibiting invasion and proliferation. In RA synoviocytes, deflazacort
      induced higher PAI-1 and lower uPA and uPAR levels, as well as a decrease in uPA
      enzymatic activity. The levels of uPAR mRNA were concomitantly reduced, as was
      uPA-induced chemoinvasion. All these effects were also shown in controls, though
      to a lesser extent. CONCLUSIONS: Deflazacort might control RA synovial
      proliferation and invasion by differential modulation of single members of the
      fibrinolytic system.

PMID- 15998635
TI  - Reactivation of mutant p53 and induction of apoptosis in human tumor cells by
      maleimide analogs.
AB  - Reactivation of mutant p53 is likely to provide important benefits for treatment
      of chemotherapy- and radiotherapy-resistant tumors. We demonstrate here that the
      maleimide-derived molecule MIRA-1 can reactivate DNA binding and preserve the
      active conformation of mutant p53 protein in vitro and restore transcriptional
      transactivation to mutant p53 in living cells. MIRA-1 induced mutant p53
      dependent cell death in different human tumor cells carrying tetracycline
      regulated mutant p53. The structural analog MIRA-3 showed antitumor activity in
      vivo against human mutant p53-carrying tumor xenografts in SCID mice. The MIRA
      scaffold is a novel lead for the development of anticancer drugs specifically
      targeting mutant p53.

PMID- 15998636
TI  - Arginine methylation of yeast mRNA-binding protein Npl3 directly affects its
      function, nuclear export, and intranuclear protein interactions.
AB  - Arginine methylation can affect both nucleocytoplasmic transport and protein
      protein interactions of RNA-binding proteins. These effects are seen in cells
      that lack the yeast hnRNP methyltransferase (HMT1), raising the question of
      whether effects on specific proteins are direct or indirect. The presence of
      multiple arginines in individual methylated proteins also raises the question of
      whether overall methylation or methylation of a subset of arginines affects
      protein function. We have used the yeast mRNA-binding protein Npl3 to address
      these questions in vivo. Matrix-assisted laser desorption/ionization Fourier
      transform mass spectrometry was used to identify 17 methylated arginines in Npl3
      purified from yeast: whereas 10 Arg-Gly-Gly (RGG) tripeptides were exclusively
      dimethylated, variable levels of methylation were found for 5 RGG and 2 RG motif
      arginines. We constructed a set of Npl3 proteins in which subsets of the RGG
      arginines were mutated to lysine. Expression of these mutant proteins as the sole
      form of Npl3 specifically affected growth of a strain that requires Hmt1.
      Although decreased growth generally correlated with increased numbers of Arg-to
      Lys mutations, lysine substitutions in the N terminus of the RGG domain showed
      more severe effects. Npl3 with all 15 RGG arginines mutated to lysine exited the
      nucleus independent of Hmt1, indicating a direct effect of methylation on Npl3
      transport. These mutations also resulted in a decreased, methylation-independent
      interaction of Npl3 with transcription elongation factor Tho2 and inhibited Npl3
      self-association. These results support a model in which arginine methylation
      facilitates Npl3 export directly by weakening contacts with nuclear proteins.

PMID- 15998637
TI  - Thrombin functions through its RGD sequence in a non-canonical conformation.
AB  - Previous studies have suggested that thrombin interacts with integrins in
      endothelial cells through its RGD (Arg-187, Gly-188, Asp-189) sequence. All
      existing crystal structures of thrombin show that most of this sequence is buried
      under the 220-loop and therefore interaction via RGD implies either partial
      unfolding of the enzyme or its proteolytic digestion. Here, we demonstrate that
      surface-absorbed thrombin promotes attachment and migration of endothelial cells
      through interaction with alpha(v)beta(3) and alpha(5)beta(1) integrins. Using
      site-directed mutants of thrombin we prove that this effect is mediated by the
      RGD sequence and does not require catalytic activity. The effect is abrogated
      when residues of the RGD sequence are mutated to Ala and is not observed with
      proteases like trypsin and tissue-type plasminogen activator, unless the RGD
      sequence is introduced at position 187-189. The potent inhibitor hirudin does not
      abrogate the effect, suggesting that thrombin functions through its RGD sequence
      in a non-canonical conformation. A 1.9-Angstroms resolution crystal structure of
      free thrombin grown in the presence of high salt (400 mm KCl) shows two molecules
      in the asymmetric unit, one of which assumes an unprecedented conformation with
      the autolysis loop shifted 20 Angstroms away from its canonical position, the 220
      loop entirely disordered, and the RGD sequence exposed to the solvent.

PMID- 15998638
TI  - Vaccinia virus protein A52R activates p38 mitogen-activated protein kinase and
      potentiates lipopolysaccharide-induced interleukin-10.
AB  - Vaccinia virus (VV) has many mechanisms to suppress and modulate the host immune
      response. The VV protein A52R was previously shown to act as an intracellular
      inhibitor of nuclear factor kappaB (NFkappaB) signaling by Toll-like receptors
      (TLRs). Co-immunoprecipitation studies revealed that A52R interacted with both
      tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1
      receptor-associated kinase 2 (IRAK2). The effect of A52R on signals other than
      NFkappaB was not determined. Here, we show that A52R does not inhibit TLR-induced
      p38 or c-Jun amino N-terminal kinase (JNK) mitogen activating protein (MAP)
      kinase activation. Rather, A52R could drive activation of these kinases. Two
      lines of evidence suggested that the A52R/TRAF6 interaction was critical for
      these effects. First, A52R-induced p38 MAP kinase activation was inhibited by
      overexpression of the TRAF domain of TRAF6, which sequestered A52R and inhibited
      its interaction with endogenous TRAF6. Second, a truncated version of A52R, which
      interacted with IRAK2 and not TRAF6, was unable to activate p38. Because
      interleukin 10 (IL-10) production is strongly p38-dependent, we examined the
      effect of A52R on IL-10 gene induction. A52R was found to be capable of inducing
      the IL-10 promoter through a TRAF6-dependent mechanism. Furthermore, A52R
      enhanced lipopolysaccharide/TLR4-induced IL-10 production, while inhibiting the
      TLR-induced NFkappaB-dependent genes IL-8 and RANTES. These results show that
      although A52R inhibits NFkappaB activation by multiple TLRs it can simultaneously
      activate MAP kinases. A52R-mediated enhancement of TLR-induced IL-10 may be
      important to virulence, given the role of IL-10 in immunoregulation.

PMID- 15998639
TI  - Activation of the BK (SLO1) potassium channel by mallotoxin.
AB  - Pharmacologic approaches to activate K+ channels represent an emerging strategy
      to regulate membrane excitability. Here we report the identification and
      characterization of a lipid soluble toxin, mallotoxin (rottlerin), which potently
      activates the large conductance voltage and Ca2+-activated K+ channel (BK)
      expressed in a heterologous expression system and human vascular smooth muscle
      cells, shifting the conductance/voltage relationship by >100 mV. Probing the
      mechanism of action, we discover that the BK channel can be activated in the
      absence of divalent cations (Ca2+, Mg2+), suggesting that the mallotoxin
      mechanism of action involves the voltage-dependent gating of the channel.
      Mallotoxin-activated channels remain incrementally sensitive to Ca2+ and beta
      subunits. In comparison to other small hydrophobic poisons, anesthetic agents,
      and protein toxins that inhibit ion channel activity, mallotoxin potently
      activates channel activity. In certain respects, mallotoxin acts as a BK channel
      beta1 subunit mimetic, preserving BK channel Ca2+ sensitivity yet adjusting the
      set-point for BK channel activation to a more hyperpolarized membrane potential.

PMID- 15998640
TI  - The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a membrane
      associated pseudophosphatase also mutated in type 4B Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth disease type 4B (CMT4B) is a severe, demyelinating peripheral
      neuropathy characterized by distinctive, focally folded myelin sheaths. CMT4B is
      caused by recessively inherited mutations in either myotubularin-related 2
      (MTMR2) or MTMR13 (also called SET-binding factor 2). MTMR2 encodes a member of
      the myotubularin family of phosphoinositide-3-phosphatases, which dephosphorylate
      phosphatidylinositol 3-phosphate (PI(3)P) and bisphosphate PI(3,5)P2. MTMR13
      encodes a large, uncharacterized member of the myotubularin family. The MTMR13
      phosphatase domain is catalytically inactive because the essential Cys and Arg
      residues are absent. Given the genetic association of both MTMR2 and MTMR13 with
      CMT4B, we investigated the biochemical relationship between these two proteins.
      We found that the endogenous MTMR2 and MTMR13 proteins are associated in human
      embryonic kidney 293 cells. MTMR2-MTMR13 association is mediated by coiled-coil
      sequences present in each protein. We also examined the cellular localization of
      MTMR2 and MTMR13 using fluorescence microscopy and subcellular fractionation. We
      found that (i) MTMR13 is a predominantly membrane-associated protein; (ii) MTMR2
      and MTMR13 cofractionate in both a light membrane fraction and a cytosolic
      fraction; and (iii) MTMR13 membrane association is mediated by the segment of the
      protein which contains the pseudophosphatase domain. This work, which describes
      the first cellular or biochemical investigation of the MTMR13 pseudophosphatase
      protein, suggests that MTMR13 functions in association with MTMR2. Loss of MTMR13
      function in CMT4B2 patients may lead to alterations in MTMR2 function and
      subsequent alterations in 3-phosphoinositide signaling. Such a mechanism would
      explain the strikingly similar phenotypes of patients with recessive mutations in
      either MTMR2 or MTMR13.

PMID- 15998641
TI  - In vivo regulation of acetylcholinesterase insertion at the neuromuscular
      junction.
AB  - The efficiency of synaptic transmission between nerve and muscle depends on the
      number and density of acetylcholinesterase molecules (AChE) at the neuromuscular
      junction. However, little is known about the way this density is maintained and
      regulated in vivo. By using time lapse and quantitative fluorescence imaging
      assays in living mice, we demonstrated that insertion of new AChEs occurs within
      hours of saturating pre-existing AChEs with fasciculin2, a snake toxin that
      selectively labels AChE. In the absence of muscle postsynaptic activity or evoked
      nerve presynaptic neurotransmitter release, AChE insertion was decreased
      significantly, whereas direct stimulation of the muscle completely restored AChE
      insertion to control levels. This activity-dependent AChE insertion is mediated
      by intracellular calcium. In muscle stimulated in the presence of a Ca2+ channel
      blocker or calcium-permeable Ca2+ chelator, AChE insertion into synapses was
      significantly decreased, whereas ryanodine or ionophore A12387 treatment of
      blocked and unstimulated synapses significantly increased AChE insertion. These
      results demonstrated that synaptic activity is critical for AChE insertion and
      indicated that a rise in intracellular calcium either through voltage-gated
      calcium channels or from intracellular stores is critical for proper AChE
      insertion into the adult synapse.

PMID- 15998642
TI  - Differential localization and identification of a critical aspartate suggest non
      redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3.
AB  - Signal peptide peptidase (SPP) is an unusual aspartyl protease that mediates
      clearance of signal peptides by proteolysis within the endoplasmic reticulum
      (ER). Like presenilins, which provide the proteolytically active subunit of the
      gamma-secretase complex, SPP contains a critical GXGD motif in its C-terminal
      catalytic center. Although SPP is known to be an aspartyl protease of the GXGD
      type, several presenilin homologues/SPP-like proteins (PSHs/SPPL) of unknown
      function have been identified by data base searches. We now investigated the
      subcellular localization and a putative proteolytic activity of PSHs/SPPLs in
      cultured cells and in an in vivo model. We demonstrate that SPPL2b is targeted
      through the secretory pathway to endosomes/lysosomes, whereas SPP and SPPL3 are
      restricted to the ER. As suggested by the differential subcellular localization
      of SPPL2b compared with SPP and SPPL3, we found distinct phenotypes upon
      antisense gripNA-mediated knockdown in zebrafish. spp and sppl3 knockdowns in
      zebrafish result in cell death within the central nervous system, whereas
      reduction of sppl2b expression causes erythrocyte accumulation in an enlarged
      caudal vein. Moreover, expression of D/A mutations of the putative C-terminal
      active sites of spp, sppl2, and sppl3 produced phenocopies of the respective
      knockdown phenotypes. Thus, our data suggest that all investigated PSHs/SPPLs are
      members of the novel family of GXGD aspartyl proteases. Furthermore, SPPL2b is
      shown to be the first member of the SPP/PSH/SPPL family that is not located
      within the ER but in endosomal/lysosomal vesicles.

PMID- 15998643
TI  - Structures of tryptophanyl-tRNA synthetase II from Deinococcus radiodurans bound
      to ATP and tryptophan. Insight into subunit cooperativity and domain motions
      linked to catalysis.
AB  - An auxiliary tryptophanyl tRNA synthetase (drTrpRS II) that interacts with nitric
      oxide synthase in the radiation-resistant bacterium Deinococcus radiodurans
      charges tRNA with tryptophan and 4-nitrotryptophan, a specific nitration product
      of nitric-oxide synthase. Crystal structures of drTrpRS II, empty of ligands or
      bound to either Trp or ATP, reveal that drTrpRS II has an overall structure
      similar to standard bacterial TrpRSs but undergoes smaller amplitude motions of
      the helical tRNA anti-codon binding (TAB) domain on binding substrates. TAB
      domain loop conformations that more closely resemble those of human TrpRS than
      those of Bacillus stearothermophilus TrpRS (bsTrpRS) indicate different modes of
      tRNA recognition by subclasses of bacterial TrpRSs. A compact state of drTrpRS II
      binds ATP, from which only minimal TAB domain movement is necessary to bring
      nucleotide in contact with Trp. However, the signature KMSKS loop of class I
      synthetases does not completely engage the ATP phosphates, and the adenine ring
      is not well ordered in the absence of Trp. Thus, progression of the KMSKS loop to
      a high energy conformation that stages acyl-adenylation requires binding of both
      substrates. In an asymmetric drTrpRS II dimer, the closed subunit binds ATP,
      whereas the open subunit binds Trp. A crystallographically symmetric dimer binds
      no ligands. Half-site reactivity for Trp binding is confirmed by thermodynamic
      measurements and explained by an asymmetric shift of the dimer interface toward
      the occupied active site. Upon Trp binding, Asp68 propagates structural changes
      between subunits by switching its hydrogen bonding partner from dimer interface
      residue Tyr139 to active site residue Arg30. Since TrpRS IIs are resistant to
      inhibitors of standard TrpRSs, and pathogens contain drTrpRS II homologs, the
      structure of drTrpRS II provides a framework for the design of potentially useful
      antibiotics.

PMID- 15998644
TI  - JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like
      growth factor and negatively regulated by suppressor of cytokine signaling-3.
AB  - Janus kinases (JAK) and signal transducers and activator of transcription (STAT)
      proteins are activated in response to many cytokines and growth factors and are
      well studied in the immune system. This study was conducted to examine the role
      of the JAK/STAT pathway in neurons in response to tumor necrosis factor-alpha
      (TNFalpha) and insulin-like growth factor-1 (IGF-1), which play a major role
      during neurodegeneration, and to study their effect on expression of suppressors
      of cytokine signaling 3 (SOCS-3), belonging to the novel family of feedback
      regulators of cytokine and growth factor activities. In this report, we showed
      that TNFalpha is inhibitory to the survival of primary cortical neurons at higher
      doses and that IGF-1 can rescue TNFalpha-stimulated cell death. We showed that
      the JAK/STAT pathway is involved in this rescue as tyrphostin AG490, a specific
      inhibitor of JAK/STAT, completely inhibits cell survival in response to IGF-1.
      STAT3 gets tyrosine-phosphorylated and translocated to the nucleus in response to
      IGF-1. Northern blot, semi-quantitative reverse transcription-PCR, and real time
      PCR experiments demonstrated that the JAK/STAT pathway also up-regulated SOCS-3
      mainly in response to IGF-1. SOCS-3 associated with the IGF receptor and blocked
      further STAT3 activation. To our knowledge, this is the first report that
      demonstrated the importance of the JAK/STAT pathway and the role of SOCS-3 in the
      survival of neurons in response to IGF-1. We have subsequently shown that SOCS-3
      overexpression, on one hand, leads to neuroblastoma cell death and on the other
      hand leads to primary cell differentiation, indicating the involvement of SOCS-3
      in cell survival and differentiation.

PMID- 15998645
TI  - Study on radon and radon progeny in some living rooms.
AB  - In the first part of this work, the potential alpha energy concentration (PAEC)
      of radon progeny, the equilibrium factor (F), the activity concentration of 222Rn
      gas (Co) and the unattached fraction (fp), were determined in 15 living rooms at
      El-Minia City, Egypt. The activity size distribution of (214)Pb was measured by
      using a low pressure Berner impactor. Based on the parameters of that
      distribution the total effective dose through the human lung was evaluated by
      using a dosimetric model calculation of ICRP. An electrostatic precipitation
      method was used for the determination of 222Rn gas concentration. The mean
      activity concentration of 222Rn gas (Co) was found to be 123 +/- 22 Bq m(-3). A
      mean unattached fraction (fp) of 0.11 +/- 0.02 was obtained at a mean aerosol
      particle concentration (Z) of (3.0 +/- 0.21) x 10(3) cm(-3). The mean equilibrium
      factor (F) was determined to be 0.35 +/- 0.03. The mean PAEC was found to be 37
      +/- 8.1 Bq m(-3). The activity size distribution of (214)Pb shows mean activity
      median diameter of 290 nm with mean geometric standard deviation (sigma) of 2.45.
      At a total deposition fraction of approximately 23% the total effective dose to
      the lung was determined to be approximately 1.2 mSv. The second part of this
      paper deals with a study of natural radionuclide contents of samples collected
      from the building materials of those rooms under investigation given in part one
      of this paper. Analyses were performed in Marinelli beakers with a gamma
      multichannel analyser provided with a NaI(Tl) detector. The samples have revealed
      the presence of the uranium-radium and thorium radioisotopes as well as (40)K.
      Nine gamma-lines of the natural radioisotopes that correspond to 212Pb, 214Pb,
      214Bi, 228Ac, 40K and 208Tl were detected and measured. The activity
      concentrations of 226Ra, 232Th and 40K were determined with mean specific
      activities of 65 +/- 22, 35 +/- 12 and 150 +/- 60 Bq kg(-1), respectively. These
      activities amount to a radium equivalent (Ra(eq)) of 126 Bq kg(-1) and to a mean
      value of external hazard index of 0.34.

PMID- 15998646
TI  - Variability in quality of care among dialysis units in western Switzerland.
AB  - BACKGROUND: Quality indicators for dialysis care vary across countries and
      regions, but regional variability across centres has received little attention.
      We analysed variations in quality indicators among dialysis facilities in western
      Switzerland to identify opportunities for improving care for patients with end
      stage kidney disease. METHODS: A cross-sectional study of 617 dialysis patients
      treated at 19 facilities examined the distribution of indicators of quality of
      care addressing: adequacy of dialysis (Kt/V > or =1.2 for haemodialysis, Kt/V >
      or =2 for peritoneal dialysis), anaemia control (haemoglobin > or =110 g/l),
      calcium and phosphate control (product < or =4.4 mmol2/l2), adequate nutrition
      (serum albumin >35 g/l), hypertension control (pre-dialysis blood pressure
      <140/90 mmHg) and type of vascular access. Centre quality targets were the
      following: achievement of quality criteria for 80% of their patients, except 85%
      for anaemia control and 60% for arterio-venous fistulae. RESULTS: Most centres
      fulfilled quality targets for dialysis adequacy, but substantial variations
      existed among centres (haemodialysis, 76%, range 36-100; peritoneal dialysis,
      76%, range 33-100). Results were similar for anaemia (77%, range 35-100), calcium
      x phosphate product (69%, range 29-92), albumin (63%, range 26-95), hypertension
      control (33%, range 13-54) and arterio-venous fistula (61%, range 49-92). The
      between-centre variability was significantly greater than would be expected by
      chance, for all indicators. Dialysis facilities with >40 patients better
      fulfilled quality targets than university-based centres. Adjustment for patient
      characteristics did not modify these results. CONCLUSIONS: Substantial variations
      in quality indicators existed between dialysis centres in western Switzerland,
      which could not be attributed to different centre policies, or to differences in
      available measures of patient case mix. These findings indicate opportunities for
      improvement in dialysis practice which may translate into improved clinical
      outcomes.

PMID- 15998647
TI  - Oxalate clearance by haemodialysis--a comparison of seven dialysers.
AB  - BACKGROUND: In patients with primary hyperoxaluria (PH) and oliguric end-stage
      renal disease, oxalate removal is largely dependent on the clearance by dialysis.
      Data on the oxalate clearance of newer dialyser types are scarce or absent.
      Therefore, we measured oxalate clearances of seven dialysers in a single 52-year
      old female patient with PH. Since haemodiafiltration (HDF) has been advocated to
      increase oxalate clearance, we also assessed the effect of different pre-dilution
      flows. The goal of the study was to select the dialyser and pre-dilution flow
      combination with the highest oxalate clearance. METHODS: Oxalate clearances were
      assessed by simultaneously taking afferent blood and efferent dialysate samples
      at 30, 60, 120 and 180 min after the start of haemodialysis. Blood flow and
      dialysate flow were 350 and 500 ml/min, respectively. All dialysers were tested
      at a pre-dilution flow of 2 l/h. Six dialysers were also tested at either a pre
      dilution flow of 4.5 l/h or without HDF, depending on the ultrafiltration
      coefficient of the dialyser. RESULTS: Oxalate clearances differed markedly
      between the tested dialysers, ranging from 144+/-10 to 220+/-12 ml/min. The
      highest oxalate clearances were achieved with HdF100S (219+/-10 ml/min) and
      Sureflux FB-210U (220+/-12 ml/min) at a pre-dilution flow of 2 l/h. Higher pre
      dilution flows (2 l/h vs no HDF or 4.5 vs 2.0 l/h) yielded similar oxalate
      clearances. CONCLUSION: The highest oxalate clearances were achieved with a high
      flux polysulfone and a cellulose triacetate dialyser with a large surface area.
      Higher pre-dilution flows did not augment oxalate clearance.

PMID- 15998648
TI  - Do dialysis- and transplantation-related medical factors affect perceived health
      status?
AB  - BACKGROUND: Quality of life and perceived health status (PHS) are important
      indicators of patient care together with morbidity, mortality and health-care
      resource utilization. The aim of this study is to explore how various medical
      conditions might influence perceived health status. METHODS: The study sample
      consisted of 128 kidney transplant recipients. PHS was measured using the self
      administered SF-36 questionnaire. Stepwise linear regression analysis of 17
      demographic, dialysis-, transplantation- and co-morbidity-related factors was
      performed in order to explore predictors of worse PHS. RESULTS: Older age, female
      gender, lower education, increased number of hospitalizations during the dialysis
      period and diabetes mellitus were identified as significant predictors of worse
      PHS. Age was the most important predictor of PHS, explaining 23.3% of variance in
      the SF-36 physical component and 4.4% in the SF-36 mental component. Between age
      groups, major differences were found in predictors of perceived health status
      serum creatinine was the most important for patients younger than 45 years and
      the number of hospitalizations for patients of 45 years and over. CONCLUSIONS:
      Biological and medical factors are significant predictors of the physical
      component of PHS, although they can explain only up to one-third of its variance.
      Other dimensions of PHS are weakly influenced by these medical parameters. It
      seems important to evaluate perceived health status separately among the age
      groups because they differ in their predictors.

PMID- 15998649
TI  - Relationship of gender, age, and body mass index to errors in predicted kidney
      function.
AB  - BACKGROUND: Previous studies have shown conflicting data on accuracy of equations
      for kidney function prediction. The present work analysed the relationship of
      gender, age and body mass index (BMI) to error of predictions by the Cockcroft
      Gault equation (CG(eq)), the simplified equation of the Modification of Renal
      Diseases Study (MDRD(eq)) and the Mayo Clinic equation (Mayo(eq)). METHODS:
      Inulin clearance (glomerular filtration rate; GFR) and other variables were
      measured in 380 subjects of both sexes, aged 18-88 years, with and without kidney
      disease. GFR was defined as low when <60 ml/min x 1.73 m2. BMI was used for
      definition of underweight/overweight. Relative error of predictions was used as
      an index of bias. It was calculated as prediction minus GFR (positive values
      =overestimates, negative values = underestimates) and expressed as a percentage
      of the GFR. Absolute error was used as an index of imprecision and was calculated
      as the absolute value of relative error. RESULTS: CG(eq) relative error was
      inversely associated with age and directly associated with BMI (P<0.001), but not
      with gender or GFR. MDRD(eq) relative error was inversely associated with female
      gender and GFR (P<0.001), but not with age or BMI. Mayo(eq) relative error was
      directly associated with male gender, BMI and GFR (P<0.01), but not with age.
      Absolute error was higher for CG(eq) than for MDRD(eq) but only at low GFR
      (P<0.001). Mayo(eq) had a higher absolute error than CG(eq) and MDRD(eq)
      (P<0.01). CONCLUSIONS: Errors of predictions varied not only with GFR but also
      with gender, age and BMI. Without using creatinine assay calibration, Mayo(eq)
      was less accurate than both MDRD(eq) and CG(eq), whereas MDRD(eq) was slightly
      more precise than CG(eq) but only at low GFR.

PMID- 15998650
TI  - Slit or pore? A mutation of the ion channel TRPC6 causes FSGS.

PMID- 15998651
TI  - Development of Graves' disease during cyclosporin treatment for severe Henoch
      Schonlein nephritis.

PMID- 15998653
TI  - Vascular access cannulation and the end of religion: is it time or our own human
      variables that determine success?

PMID- 15998652
TI  - Effects of different energy intakes on nitrogen balance in patients with acute
      renal failure: a pilot study.
AB  - BACKGROUND: Thus far, there have been no controlled studies to examine optimal
      levels of energy provision in critically ill patients with acute renal failure
      (ARF) receiving artificial nutrition. METHODS: After a 24 h nitrogen-free regimen
      (20% dextrose), we assigned during an open-label, AB/BA-crossover-trial, 10 ARF
      patients receiving both total parenteral nutrition (TPN) and renal replacement
      therapy (seven males; mean age 72 years, range 60-83; mean APACHE II score 27.1,
      range 23-34, mechanical ventilation 8/10) to a lower calorie-TPN regimen (30
      kcal/kg/day) and to a higher calorie-TPN regimen (40 kcal/kg/day), each for 3
      days. Nitrogen intake was 0.25 g/kg/day for both regimens. We estimated nitrogen
      balance, protein catabolic rate and urea generation rate by urea kinetic methods
      based on both timed blood samples of serum urea and direct urea quantification
      from dialysis fluid. RESULTS: Two patients were excluded from the analysis (due
      to death and serum triglycerides above 5.1 mmol/l, respectively). Compared with
      the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated
      nitrogen balance [+1.55 g/day (95% confidence interval: -0.95 to +4.05, P =
      0.18)], protein catabolic rate [-0.10 g/kg/day (-0.33 to +0.14, P = 0.35)], or
      urea generation rate [-1.3 mg/min (-5.2 to +2.7, P = 0.46)], whereas it increased
      serum triglycerides [+1.36 mmol/l (+0.53 to +2.19, P = 0.007)], glucose [+1.15
      mmol/l (+0.07 to +2.24, P = 0.041)], insulin need [+20.4 U/day (+8.3 to +32.6, P
      = 0.006)] and nutritional fluid administration [+468 ml/day (+370 to +566,
      P<0.001)]. CONCLUSIONS: The present study, conducted in a small group of
      subjects, shows that in critically ill patients with ARF on a nitrogen intake of
      0.25 g/kg/day, an energy provision of 40 kcal/kg/day does not improve nitrogen
      balance estimates compared with a 30 kcal/kg/day intake; instead, it may increase
      the risk of artificial nutrition-related side-effects.

PMID- 15998654
TI  - Caspofungin is less nephrotoxic than amphotericin B in vitro and predominantly
      damages distal renal tubular cells.
AB  - BACKGROUND: Caspofungin (CAS) has recently been approved for treatment of
      invasive aspergillosis. In clinical trials, CAS-induced nephrotoxicity was
      markedly less pronounced compared to amphotericin B (AmB). Nevertheless, in a
      recent trial, nephrotoxicity in CAS-treated patients was considerably more
      pronounced than in preceding studies. Therefore, the aim of this study was to
      assess toxic effects of CAS on human renal proximal and distal tubular epithelial
      cells (PTC and DTC) in vitro, and to compare them to those of AmB. METHODS: Cells
      were isolated from human kidney tissue, and exposed to clinically relevant
      concentrations of CAS and AmB for 24 h. Total DNA content and cell viability were
      determined by DAPI staining and a modified MTT assay. For testing of
      cytotoxicity, LDH activity was measured in cell culture supernatants. To assess
      apoptotic effects, AnnexinV-binding assay and DAPI staining for detection of
      fragmented DNA were performed. RESULTS: DTC were more vulnerable towards the
      antifungal agents than PTC. In contrast to AmB, cell-damaging effects of CAS were
      less severe. DAPI staining revealed slight and dose-dependent antiproliferative
      effects of CAS at concentrations reflecting relevant plasma levels. At these
      concentrations, cell viability, determined by MTT assay, was not decreased in PTC
      and DTC. LDH release was marginally increased in a dose-dependent manner;
      apoptosis was not detected. Nevertheless, at CAS concentrations reflecting
      potential tissue concentrations, cell damaging effects were considerably more
      pronounced. CONCLUSION: Our results suggest that CAS is less nephrotoxic than AmB
      in vitro. The antiproliferative and cytotoxic effects of CAS predominantly affect
      DTC, which seem to be more susceptible to CAS-induced damage.

PMID- 15998655
TI  - Online measurement of haemoglobin concentration.
AB  - BACKGROUND: Regular monitoring of haemoglobin in chronic haemodialysis patients
      is essential to ensure that targets for anaemia management are consistently
      achieved. Repeated blood sampling can be time consuming, invasive and, for
      pragmatic reasons, only infrequently performed, often delaying therapeutic
      change. On-line optical continuous monitoring of the haemoglobin concentration
      would allow non-invasive assessment of haemoglobin, and immediate therapeutic
      changes could be implemented, thereby improving the efficiency of anaemia
      management. This study aimed to evaluate the use of on-line haemoglobin
      concentration measurement. METHODS: Eleven dialysis monitors (Integra Hospal)
      were calibrated using at least five haemoglobin samples spread over at least 4
      g/dl. Optical measurement of haemoglobin concentration is already incorporated
      into the dialysis monitor to allow the study of relative blood volume. Fifteen
      patients were studied with paired haemoglobin measurements (i.e. dialysis monitor
      value and conventional laboratory assessment) taken at intervals over 7 months
      (mean 11.0+/-0.28 g/dl, range 7.5-14.8). RESULTS: Haemoglobin measured by
      Hemoscan correlated well with the laboratory measurements (r2 = 0.83, P<0.0001),
      indicating that the machine values are broadly comparable with laboratory
      figures. There was a mean underestimate of haemoglobin by Hemoscan of 0.34%.
      There was no significant deterioration in the quality of this correlation over
      the study period (r2>0.8). CONCLUSION: The ability of the dialysis monitor to
      measure the optical concentration of haemoglobin compared with conventional
      laboratory assessment is both precise and accurate. Regular on-line assessment of
      haemoglobin may allow more proactive micromanagement of renal anaemia, with a
      reduction in the time taken to achieve clinically important targets and give
      early warning of suboptimal response to treatment.

PMID- 15998656
TI  - Why thermosensing? A primer on thermoregulation.

PMID- 15998657
TI  - Effects of antioxidant supplementation on blood cyclosporin A and glomerular
      filtration rate in renal transplant recipients.
AB  - BACKGROUND: Transplant recipients have elevated oxidative stress, which has
      prompted suggestions that supplementary antioxidants may be beneficial. However,
      only a small number of clinical trials have investigated antioxidant
      supplementation in transplant recipients, with very few data on their effects on
      patients' immunosuppressive therapy. METHODS: A randomized placebo-controlled
      single-blind crossover trial was conducted in 10 renal transplant recipients
      (RTRs) taking cyclosporin A (CsA) as part of their immunosuppressive therapy.
      Each phase of the trial lasted 6 months, with a 6 month wash-out period in
      between. During one of the phases, patients consumed a tablet twice per day which
      delivered 400 IU/day of vitamin E, 500 mg/day of vitamin C and 6 mg/day of beta
      carotene. RESULTS: During antioxidant supplementation, there was no change in CsA
      dose. Antioxidant supplementation resulted in a significant decrease (P<0.05) in
      blood trough CsA by 24% (mean+/-SD, pre- 127.3+/-38.9, post- 97.2+/-30.7
      microg/ml) compared with no change while taking the placebo (pre- 132.2+/-50.6,
      post- 138.6+/-56.0 microg/ml). The glomerular filtration rate was significantly
      (P<0.05) improved by 12% during antioxidant supplementation (pre- 66.9+/-20.7,
      post- 75.0+/-20.1 ml/min/1.72 m2), with no change during the placebo phase (pre-
      66.8+/-11.8, post- 66.7+/-16.1 ml/min/1.72 m2). There were no significant
      differences (P>0.05) in markers of oxidative stress (malondialdehyde,
      susceptibility of plasma to oxidation) or plasma antioxidant enzymes. CONCLUSION:
      In CsA-treated RTRs, antioxidant supplementation decreased blood CsA, which may
      affect adequacy of immunosuppression.

PMID- 15998658
TI  - A common mitchondrial DNA variant is associated with thinness in mothers and
      their 20-yr-old offspring.
AB  - A common mitochondrial (mt)DNA variant that is maternally inherited, the 16189
      variant, is associated with type 2 diabetes and thinness at birth. To elucidate
      the association of the variant with thinness, we studied the 16189 variant in a
      well-characterized Australian cohort (n = 161) who were followed up from birth to
      age 20 yr. PCR analysis and mtDNA haplotyping was carried out on DNA from 161
      offspring from consecutive, normal, singleton pregnancies followed from birth to
      age 20 yr. The 16189 mtDNA variant was present in 14 of the 161 20 yr olds
      (8.7%). Both the mothers with the 16189 variant and their 20-yr-old offspring
      were thinner than those without. Median (interquartile range) BMI was 21.9
      kg/m(2) (20.4 to 22.9) in mothers with the variant compared with 23.5 (21.4 to
      26.6) in those without (P = 0.013) and 22.2 (21.1 to 23.8) in 20 yr olds with the
      variant compared with 22.7 (20.8 to 25.6) in those without (P = 0.019). The 16189
      variant was also associated with a high placental weight and high placental-to
      birth weight ratio (P = 0.051 and P = 0.0024, respectively). Insulin sensitivity
      was normal in 20 yr olds with the 16189 variant. This contrasts with 20 yr olds
      who did not have the variant but who had been thin or small at birth and who had
      normal BMI and normal placental-to-birth weight ratio, but were insulin
      resistant. This study suggests that the 16189 mtDNA variant is associated with
      maternally inherited thinness in young adults. This may be mediated by effects on
      mtDNA replication and, thence, placental function. Further research is required
      to confirm these hypotheses.

PMID- 15998659
TI  - Fat digestion is required for suppression of ghrelin and stimulation of peptide
      YY and pancreatic polypeptide secretion by intraduodenal lipid.
AB  - Stimulation of cholecystokinin and glucagon-like peptide-1 secretion by fat is
      mediated by the products of fat digestion. Ghrelin, peptide YY (PYY), and
      pancreatic polypeptide (PP) appear to play an important role in appetite
      regulation, and their release is modulated by food ingestion, including fat. It
      is unknown whether fat digestion is a prerequisite for their suppression
      (ghrelin) or release (PYY, PP). Moreover, it is not known whether small
      intestinal exposure to fat is sufficient to suppress ghrelin secretion. Our study
      aimed to resolve these issues. Sixteen healthy young males received, on two
      separate occasions, 120-min intraduodenal infusions of a long-chain triglyceride
      emulsion (2.8 kcal/min) 1) without (condition FAT) or 2) with (FAT-THL) 120 mg of
      tetrahydrolipstatin (THL, lipase inhibitor), followed by a standard buffet-style
      meal. Blood samples for ghrelin, PYY, and PP were taken throughout. FAT infusion
      was associated with a marked, and progressive, suppression of plasma ghrelin from
      t = 60 min (P < 0.001) and stimulation of PYY from t = 30 min (P < 0.01). FAT
      infusion also stimulated plasma PP (P < or = 0.01), and the release was
      immediate. FAT-THL completely abolished the FAT-induced changes in ghrelin, PYY,
      and PP. In response to the meal, plasma ghrelin was further suppressed, and PYY
      and PP stimulated, during both FAT and FAT-THL infusions. In conclusion, in
      healthy humans, 1) the presence of fat in the small intestine suppresses ghrelin
      secretion, and 2) fat-induced suppression of ghrelin and stimulation of PYY and
      PP is dependent on fat digestion.

PMID- 15998660
TI  - Acute inhibition of lipolysis does not affect postprandial suppression of
      endogenous glucose production.
AB  - To test the hypothesis that intrahepatic availability of fatty acid could modify
      the rate of suppression of endogenous glucose production (EGP), acipimox or
      placebo was administered before and during a test meal. We used a modified
      isotopic methodology to measure EGP in 11 healthy subjects, and (1)H magnetic
      resonance spectroscopic measurement of hepatic triglyceride stores was also
      undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal
      (0.05 +/- 0.01 mmol/l at -10 min, P = 0) and throughout the postprandial period
      (0.03 +/- 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly
      lower after the meal on acipimox days (8.9 +/- 0.4 vs. 10.1 +/- 0.5 mmol/l, P <
      0.01), as was mean peak serum insulin (653.1 +/- 99.9 vs. 909 +/- 118 pmol/l, P <
      0.01). Fasting EGP was similar (11.15 +/- 0.58 micromol.kg(-1).min(-1) placebo
      vs. 11.17 +/- 0.89 mg.kg(-1).min(-1) acipimox). The rate of suppression of EGP
      after the meal was almost identical on the 2 test days (4.36 +/- 1.52 vs. 3.69 +/
      1.21 micromol.kg(-1).min(-1) at 40 min). There was a significant negative
      correlation between the acipimox-induced decrease in peak plasma glucose and
      liver triglyceride content (r = -0.827, P = 0.002), suggesting that, when levels
      of liver fat were low, inhibition of lipolysis was able to affect glucose
      homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride
      stores improves postprandial glucose homeostasis without effect on the immediate
      postprandial suppression of EGP.

PMID- 15998661
TI  - Increased power of microarray analysis by use of an algorithm based on a
      multivariate procedure.
AB  - MOTIVATION: The power of microarray analyses to detect differential gene
      expression strongly depends on the statistical and bioinformatical approaches
      used for data analysis. Moreover, the simultaneous testing of tens of thousands
      of genes for differential expression raises the 'multiple testing problem',
      increasing the probability of obtaining false positive test results. To achieve
      more reliable results, it is, therefore, necessary to apply adjustment procedures
      to restrict the family-wise type I error rate (FWE) or the false discovery rate.
      However, for the biologist the statistical power of such procedures often remains
      abstract, unless validated by an alternative experimental approach. RESULTS: In
      the present study, we discuss a multiplicity adjustment procedure applied to
      classical univariate as well as to recently proposed multivariate gene-expression
      scores. All procedures strictly control the FWE. We demonstrate that the use of
      multivariate scores leads to a more efficient identification of differentially
      expressed genes than the widely used MAS5 approach provided by the Affymetrix
      software tools (Affymetrix Microarray Suite 5 or GeneChip Operating Software).
      The practical importance of this finding is successfully validated using real
      time quantitative PCR and data from spike-in experiments. AVAILABILITY: The R
      code of the statistical routines can be obtained from the corresponding author.
      CONTACT: Schuster@imise.uni-leipzig.de

PMID- 15998662
TI  - Local modeling of global interactome networks.
AB  - MOTIVATION: Systems biology requires accurate models of protein complexes,
      including physical interactions that assemble and regulate these molecular
      machines. Yeast two-hybrid (Y2H) and affinity-purification/mass-spectrometry (AP
      MS) technologies measure different protein-protein relationships, and issues of
      completeness, sensitivity and specificity fuel debate over which is best for high
      throughput 'interactome' data collection. Static graphs currently used to model
      Y2H and AP-MS data neglect dynamic and spatial aspects of macromolecular
      complexes and pleiotropic protein function. RESULTS: We apply the local modeling
      methodology proposed by Scholtens and Gentleman (2004) to two publicly available
      datasets and demonstrate its uses, interpretation and limitations. Specifically,
      we use this technology to address four major issues pertaining to protein-protein
      networks. (1) We motivate the need to move from static global interactome graphs
      to local protein complex models. (2) We formally show that accurate local
      interactome models require both Y2H and AP-MS data, even in idealized situations.
      (3) We briefly discuss experimental design issues and how bait selection affects
      interpretability of results. (4) We point to the implications of local modeling
      for systems biology including functional annotation, new complex prediction,
      pathway interactivity and coordination with gene-expression data. AVAILABILITY:
      The local modeling algorithm and all protein complex estimates reported here can
      be found in the R package apComplex, available at http://www.bioconductor.org
      CONTACT: dscholtens@northwestern.edu SUPPLEMENTARY INFORMATION:
      http://daisy.prevmed.northwestern.edu/~denise/pubs/LocalModeling

PMID- 15998663
TI  - A precise and scalable method for querying genes in chromosomal banding regions
      based on cytogenetic annotations.
AB  - MOTIVATION: Staining the human metaphase chromosomes reveals characteristic
      banding patterns known as cytogenetic bands or cytobands. Using technologies
      based on metaphase chromosomes, researchers have accumulated much knowledge about
      the correlations between human diseases and specific cytoband aberrations,
      indicating the presence of disease-associated genes in those bands. With the
      progress of human genome project and techniques such as fluorescent in situ
      hybridization, many genes have been assigned to the cytobands and annotated in
      public databases, making it possible to find all genes in the disease-related
      cytobands through database queries. However, finding genes in cytobands remains
      an imprecise process, partly due to the insufficiency of current methods for
      cytoband queries, especially for those based on cytogenetic annotations. RESULTS:
      By transforming the cytoband annotations into numerical segments, a new query
      method is developed that is able to accurately define any cytogenetic ranges in
      human chromosomes. A query system (designated cytoband query sys CQS) is
      implemented using cytogenetic annotations in the public domain. Judged by a
      performance test, CQS executed as accurately as expected using cytogenetic
      annotations from NCBI Map Viewer. The new method is scalable and can be applied
      to genomes from other species. AVAILABILITY: The CQS is freely accessible over
      the Internet at http://moris.csie.ncku.edu.tw/cqs/ CONTACT: clh9@mail.ncku.edu.tw
      SUPPLEMENTARY INFORMATION: http://moris.csie.ncku.edu.tw/cqs/

PMID- 15998664
TI  - Discrimination of yeast genes involved in methionine and phosphate metabolism on
      the basis of upstream motifs.
AB  - MOTIVATION: In yeast, methionine and phosphate metabolism are regulated by the
      complexes Met4p/Met28p/Cbf1p and Pho4p, respectively. The binding sites for these
      factors share a common core CACGTG. We evaluate our capability to discriminate
      phosphate- and methionine-responding genes on the basis of putative regulatory
      elements, despite the similarity between Met4p/Met28p/Cbf1p and Pho4p consensus.
      RESULTS: We scanned upstream regions of methionine, phosphate and control genes
      with position-specific weight matrices for Pho4p, Met4p/Met28p/Cbf1p and
      Met31p/Met32p, and applied discriminant analysis to classify genes according to
      matrix matching scores. This analysis showed that matrix scores provided a good
      discrimination between phosphate, methionine and control genes. The optimal
      parameters have then been used to predict phosphate and methionine regulation at
      a genome scale. The genome-scale analysis predicts 37 genes as methionine
      regulated and 40 as phosphate-regulated. We compare the predictive results with
      high throughput data and discuss the difference. AVAILABILITY: The programs for
      sequence retrieval and analysis, as well as the complete data and results, are
      available on the website on regulatory sequence analysis tools
      (http://rsat.scmbb.ulb.ac.be/rsat/). CONTACT: jvanheld@scmbb.ulb.ac.be
      SUPPLEMENTARY INFORMATION: The complete datasets and results are available at
      http://rsat.scmbb.ulb.ac.be/rsat/data/published_data/Gonze_MET_PHO/

PMID- 15998666
TI  - Efalizumab for the treatment of moderate to severe plaque psoriasis.
AB  - OBJECTIVE: To review the pharmacology, efficacy, and safety of efalizumab for the
      treatment of moderate to severe plaque psoriasis. DATA SOURCES: A MEDLINE search
      (1966-May 2005) using the key words hu1124, anti-CD11a, efalizumab, Raptiva,
      Xanelim, and psoriasis was conducted. References of identified articles were
      reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical
      trials evaluating the pharmacology, efficacy, and safety of efalizumab for
      treatment of moderate to severe plaque psoriasis in adults were included in our
      review. DATA SYNTHESIS: Efalizumab's ability to inhibit the binding of CD11a, a
      subunit of leukocyte function-associated antigen type 1, to intracellular
      adhesion molecule 1 results in decreased T-cell activation and migration, 2 key
      steps in the immunopathogenesis of psoriasis. Results of clinical trials have
      demonstrated that efalizumab administered subcutaneously is a safe and effective
      treatment for moderate to severe plaque psoriasis. Efalizumab was well tolerated
      in trials, with the majority of adverse events arising with the first dose and
      decreasing with subsequent doses. The high cost of this agent and lack of head-to
      head trials with other drugs will likely restrict its use to patients who have
      failed prior systemic therapy or phototherapy. CONCLUSIONS: Efalizumab is a safe
      and effective therapy for treatment of moderate to severe plaque psoriasis in
      patients who have failed prior systemic therapy or phototherapy.

PMID- 15998665
TI  - SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the
      prophase arrest of Atm-/- spermatocytes.
AB  - SPO11 introduces double-strand breaks (DSBs) that trigger the phosphorylation of
      H2AX during meiotic prophase. In mice, SPO11 is strictly required for initiation
      of meiotic recombination and synapsis, yet SPO11 is still considered to be
      dispensable for sex-body formation in mouse spermatocytes. We provide conclusive
      evidence showing that functional SPO11, and consequently recombination and
      synapsis, are required for phosphorylation of H2AX in the X-Y chromatin and for
      sex-body formation in mouse spermatocytes. We investigated the role in meiosis of
      the three kinases [ATM (ataxia telangiectasia mutated), ATR (ataxia
      telangiectasia- and Rad-3-related) and DNA-PKcs (DNA-dependent-protein-kinase
      catalytic subunit)] known to phosphorylate H2AX in mitotic cells. We found that
      DNA-PKcs can be ruled out as an essential kinase in this process, whereas ATM is
      strictly required for the chromatin-wide phosphorylation of H2AX occurring in
      leptotene spermatocytes in response to DSBs. Remarkably, we discovered that Spo11
      heterozygosity can rescue the prophase-I-arrest characteristic of ATM-deficient
      spermatocytes. Characterization of the rescued Atm-/- Spo11+/- mutant indicates
      that ATM is dispensable for sex-body formation and phosphorylation of H2AX in
      this subnuclear domain. The co-localization of ATR, phosphorylated H2AX and the
      sex chromatin observed in the Atm-/- Spo11+/- mutant, along with ATR
      transcription kinetics during the first wave of spermatogenesis, confirm and
      expand recent findings indicating that ATR is the kinase involved in H2AX
      phosphorylation in the sex body.

PMID- 15998667
TI  - Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic
      patients.
AB  - BACKGROUND: In diabetic patients, postprandial hyperglycemia is a more powerful
      risk factor for cardiovascular disease than fasting hyperglycemia itself. A
      negative influence of acute hyperglycemia on systemic endothelial function
      (brachial artery) has been shown. However, myocardial perfusion during
      postprandial hyperglycemia has not been investigated. METHODS AND RESULTS: We
      evaluated the effects of a standardized mixed meal on myocardial perfusion in 20
      healthy subjects and 20 consecutive patients with type 2 diabetes mellitus
      without macrovascular or microvascular complications. Myocardial perfusion was
      assessed in fasting and postprandial states by myocardial contrast
      echocardiography. Fasting myocardial flow velocity (beta, 0.65+/-0.27 versus
      0.67+/-0.24; P=NS), myocardial blood volume (MBV; 8.3+/-1.2 versus 8.4+/-2;
      P=NS), and myocardial blood flow (5.4+/-1.5 versus 5.6+/-2; P=NS) did not differ
      between control subjects and diabetic patients. In the postprandial state, beta
      (0.67+/-0.24 versus 0.92+/-0.35; P<0.01), MBV (8.4+/-2 versus 10.9+/-2.7;
      P<0.01), and myocardial blood flow (5.6+/-2 versus 9.9+/-2.8; P<0.01) increased
      significantly in control subjects. In diabetic patients, beta increased (0.65+/
      0.27 versus 0.8+/-0.24; P<0.01) but MBV (8.3+/-1.2 versus 4.3+/-1.3; P<0.01) and
      myocardial blood flow (5.4+/-1.5 versus 3.4+/-0.9; P<0.01) decreased
      significantly. Changes in MBV (expressed as [(MBV(postprandial)
      MBV(fasting))/MBV(fasting)]x100) were significantly correlated with postprandial
      glycemia levels in diabetic patients. CONCLUSIONS: Postprandial hyperglycemia
      determines myocardial perfusion defects in type 2 diabetic patients. They are
      secondary to deterioration in microvascular function causing a decrease in MBV.
      In diabetic patients without microvascular or macrovascular complications,
      postprandial myocardial perfusion defects may represent an early marker of the
      atherogenic process in the coronary circulation; hence, its reversal constitutes
      a potential goal of treatment.

PMID- 15998668
TI  - Muscle sympathetic nerve activity averaged over 1 minute parallels renal and
      cardiac sympathetic nerve activity in response to a forced baroreceptor pressure
      change.
AB  - BACKGROUND: Despite the accumulated knowledge of human muscle sympathetic nerve
      activity (SNA) as measured by microneurography, whether muscle SNA parallels
      renal and cardiac SNAs remains unknown. METHOD AND RESULTS: In experiment 1,
      muscle (microneurography, tibial nerve), renal, and cardiac SNAs were recorded in
      anesthetized rabbits (n=6) while arterial pressure was changed by intravenous
      bolus injections of nitroprusside (3 microg/kg) followed by phenylephrine (3
      microg/kg). In experiment 2, the carotid sinus region was vascularly isolated in
      anesthetized, vagotomized, and aorta-denervated rabbits (n=10). The 3 SNAs were
      recorded while intracarotid sinus pressure was increased stepwise from 40 to 160
      mm Hg in 20-mm Hg increments maintained for 60 seconds each. Muscle SNA averaged
      over 1 minute was well correlated with renal (r=0.96+/-0.01, mean+/-SE) and
      cardiac (r=0.96+/-0.01) SNAs in experiment 1 (baroreflex closed-loop condition)
      and also with renal (r=0.97+/-0.01) and cardiac (r=0.97+/-0.01) SNAs in
      experiment 2 (baroreflex open-loop condition). CONCLUSIONS: Muscle SNA averaged
      over 1 minute parallels renal and cardiac SNAs in response to a forced
      baroreceptor pressure change.

PMID- 15998669
TI  - L-selectin-mediated neutrophil recruitment in experimental rodent aneurysm
      formation.
AB  - BACKGROUND: This investigation tested the hypothesis that L-selectin is important
      in experimental abdominal aortic aneurysm (AAA) formation in rodents. METHODS AND
      RESULTS: Rat abdominal aortas were perfused with saline (control) or porcine
      pancreatic elastase and studied on postperfusion days 1, 2, 4, 7, and 14 (n=5 per
      treatment group per day). Neutrophil (polymorphonucleur leukocyte, PMN) and
      macrophage counts per high-powered field (HPF) were performed on fixed sections.
      L-selectin expression and protein levels in aortic tissue were determined by
      polymerase chain reaction and Western blot, respectively. Elastase-perfused
      aortic diameters were significantly increased compared with control aortas at all
      time points except day 1 (P<0.05). PMN counts significantly increased in elastase
      perfused aortas compared with control aortas at days 1, 2, and 4, reaching
      maximum levels at day 7 (40.8 versus 0.3 PMNs/HPF, P=0.001). L-selectin mRNA
      expression in elastase-perfused aortas was 18 (P=0.018), 17 (P<0.001), and 8
      times (P=0.02) times greater than control aortas at days 1, 2, and 4,
      respectively. Western blot demonstrated a significant 69% increase in L-selectin
      protein at day 7 in elastase- as compared with saline-perfused aortas (P=0.005).
      Subsequent experiments involved similar studies on postperfusion days 4, 7, and
      14 of aortas from C57BL/6 wild-type (WT) mice (n=21) and L-selectin-knockout
      (LKO) mice (n=19). LKO mice had significantly smaller aortic diameters at day 14
      as compared with WT mice (88% versus 123%, P=0.02). PMN counts were significantly
      greater in elastase-perfused WT mouse aortas as compared with LKO mouse aortas at
      day 4 after perfusion (12.8 versus 4.8 PMNs/HPF, P=0.02). Macrophage counts were
      significantly greater at all time points after perfusion in elastase-perfused WT
      mouse aortas compared with elastase-perfused LKO mouse aortas, with a maximum
      difference at day 7 after perfusion (13.3 versus 0.5 macrophages/HPF, P<0.001).
      CONCLUSIONS: L-selectin-mediated neutrophil recruitment may be a critical early
      step in AAA formation.

PMID- 15998670
TI  - Targeted deletion of Fgl-2/fibroleukin in the donor modulates immunologic
      response and acute vascular rejection in cardiac xenografts.
AB  - BACKGROUND: Xenografts ultimately fail as a result of acute vascular rejection
      (AVR), a process characterized by intravascular thrombosis, fibrin deposition,
      and endothelial cell activation. METHODS AND RESULTS: We studied whether targeted
      deletion of Fgl-2, an inducible endothelial cell procoagulant, (Fgl-2-/-) in the
      donor prevents AVR in a mouse-to-rat cardiac xenotransplantation model. By 3 days
      after transplant, Fgl-2+/+ grafts developed typical features of AVR associated
      with increased levels of donor Fgl-2 mRNA. Grafts from Fgl-2-/- mice had reduced
      fibrin deposition but developed cellular rejection. Treatment with a short course
      of cobra venom factor and maintenance cyclosporine resulted in long-term
      acceptance of both Fgl-2+/+ and Fgl-2-/- grafts. On withdrawal of cyclosporine,
      Fgl-2+/+ grafts developed features of AVR; in contrast, Fgl-2-/- grafts again
      developed acute cellular rejection. Rejecting Fgl-2+/+ hearts stained positively
      for IgG, IgM, C3, and C5b-9, whereas rejecting Fgl-2-/- hearts had minimal Ig and
      complement deposition despite xenoantibodies in the serum. Furthermore, serum
      containing xenoantibodies failed to stain Fgl-2-/- long-term treated hearts but
      did stain wild-type heart tissues. Treatment of Fgl-2-/- xenografts with
      mycophenolate mofetil and tacrolimus, a clinically relevant immune suppression
      protocol, led to long-term graft acceptance. CONCLUSIONS: Deletion of Fgl-2
      ameliorates AVR by downregulation of xenoantigens and may facilitate successful
      clinical heart xenotransplantation.

PMID- 15998671
TI  - Exercise testing in asymptomatic adults: a statement for professionals from the
      American Heart Association Council on Clinical Cardiology, Subcommittee on
      Exercise, Cardiac Rehabilitation, and Prevention.
AB  - Along with coronary artery calcium scanning, ankle-brachial index measurement,
      and carotid artery ultrasound, exercise electrocardiography has been proposed as
      a screening tool for asymptomatic subjects thought to be at intermediate risk for
      developing clinical coronary disease. A wealth of data indicate that exercise
      testing can be used to assess and refine prognosis, particularly when emphasis is
      placed on nonelectrocardiographic measures such as exercise capacity,
      chronotropic response, heart rate recovery, and ventricular ectopy. Nevertheless,
      randomized trial data on the clinical value of screening exercise testing are
      absent; that is, it is not known whether a strategy of routine screening exercise
      testing in selected subjects reduces the risk for premature mortality or major
      cardiac morbidity. The writing group believes that a large-scale randomized trial
      of such a strategy should be performed.

PMID- 15998672
TI  - Heritability and a genome-wide linkage scan for arterial stiffness, wave
      reflection, and mean arterial pressure: the Framingham Heart Study.
AB  - BACKGROUND: Arterial stiffness and mean arterial pressure variably contribute to
      systolic hypertension and increased cardiovascular risk. However, few prior
      community-based studies have evaluated the genetics of arterial stiffness and
      separate mean and pulsatile components of blood pressure. METHODS AND RESULTS:
      Using arterial tonometry, we evaluated heritability and linkage of forward and
      reflected wave amplitude, mean arterial pressure, and carotid-femoral pulse wave
      velocity (CFPWV) in 1480 participants representing 817 pedigrees in the
      Framingham Study offspring cohort. In 204 families with tonometry data, a genome
      wide scan was performed with microsatellite markers that covered the genome at 10
      cM intervals. Heritability estimates were moderate for reflected wave amplitude
      (h2=0.48), forward wave amplitude (h2=0.21), CFPWV (h2=0.40), and mean arterial
      pressure (h2=0.33). Variance components linkage analysis identified 2 regions of
      linkage for reflected wave amplitude: chromosome 4 at 181 cM (logarithm of odds
      [LOD]=4.93, permuted P=0.002) and chromosome 8 at 33 cM (LOD=3.27, permuted
      P=0.058). There was 1 region of linkage for forward wave amplitude on chromosome
      7 at 174 cM (LOD=2.88, permuted P=0.017). There were several regions of
      suggestive linkage for CFPWV: chromosome 2 at 94 cM (LOD=2.46), chromosome 7 at
      29 cM (LOD=2.50), chromosome 13 at 108 cm (LOD=2.10), and chromosome 15 at 108 cM
      (LOD=2.48). There was 1 region of suggestive linkage for mean arterial pressure
      on chromosome 1 at 192 cM (LOD=2.18). CONCLUSIONS: Arterial stiffness measures
      and mean and pulsatile components of blood pressure are heritable and appear to
      have genetic determinants that may be linked to separate genetic loci in humans.

PMID- 15998673
TI  - Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium:
      short- and long-term effects.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to replace infarct
      scar, but the long-term effects are unknown. We studied short- and long-term
      effects of MSC transplantation on left ventricular (LV) function in a rat
      myocardial infarction model. METHODS AND RESULTS: Saline (n=46) or MSCs labeled
      with 1,1'-dioctadecyl-3,3,3'3'-testramethylindocarbocyanine perchlorate (DiI;
      n=49, 2x10(6) cells each) were injected into the scar of a 1-week-old myocardial
      infarction in Fischer rats. The presence and differentiation of engrafted cells
      and their effect on LV ejection fraction was assessed. At 4 weeks, LV stroke
      volume was significantly greater in the MSC-treated group (145+/-9 microL) than
      in the saline group (122+/-3 microL, P=0.032), and LV ejection fraction was
      significantly greater in MSC-treated animals (43.8+/-1.0%) than in the saline
      group (38.8+/-1.1%, P=0.0027). However, at 6 months, these benefits of MSC
      treatment were lost. DiI-positive cells were observed in the MSC group at 2 weeks
      and at 3 and 6 months. Expression of the muscle-specific markers alpha-actinin,
      myosin heavy chain, phospholamban, and tropomyosin was not observed at 2 weeks in
      DiI-positive cells. At 3 and 6 months, the DiI-positive cells were observed to
      express the above muscle-specific markers, but they did not fully evolve into an
      adult cardiac phenotype. Some of the DiI-positive cells expressed von Willebrand
      factor. CONCLUSIONS: Allogeneic MSCs survive in infarcted myocardium as long as 6
      months and express markers that suggest muscle and endothelium phenotypes. MSCs
      improved global LV function at 4 weeks; however, this benefit was transient,
      which suggests a possible early paracrine effect.

PMID- 15998675
TI  - Sudden unexplained death: heritability and diagnostic yield of cardiological and
      genetic examination in surviving relatives.
AB  - BACKGROUND: Sudden death mostly follows from cardiac disorders that elicit lethal
      ventricular arrhythmias. In young individuals, it often remains unexplained
      because history and/or postmortem analysis are absent or provide no clue. Because
      such sudden unexplained deaths (SUDs) may have heritable causes, cardiological
      and genetic assessment of surviving relatives of SUD victims may reveal the
      underlying disease and unmask presymptomatic carriers. We aimed to establish the
      diagnostic yield of such assessments. METHODS AND RESULTS: We investigated 43
      consecutive families with > or =1 SUD victim who died at < or =40 years of age.
      All studied relatives underwent resting/exercise ECG and Doppler
      echocardiography. Molecular genetic analysis was conducted to confirm the
      diagnosis. We identified an inherited disease and likely cause of death in 17 of
      43 families (40%). Twelve families had primary electrical disease:
      catecholaminergic polymorphic ventricular tachycardia (5 families), long-QT
      syndrome (4 families), Brugada syndrome (2 families), and long-QT/Brugada
      syndrome (1 family). Furthermore, we found arrhythmogenic right ventricular
      cardiomyopathy (3 families), hypertrophic cardiomyopathy (1 family), and familial
      hypercholesterolemia (1 family). Molecular genetic analysis provided confirmation
      in 10 families. Finding the diagnosis was more likely when more relatives were
      examined and in families with > or =2 SUD victims < or =40 years of age. The
      resting/exercise ECG had a high diagnostic yield. These efforts unmasked 151
      presymptomatic disease carriers (8.9 per family). CONCLUSIONS: Examination of
      relatives of young SUD victims has a high diagnostic yield, with identification
      of the disease in 40% of families and 8.9 presymptomatic carriers per family.
      Simple procedures (examining many relatives) and routine tests (resting/exercise
      ECG) constitute excellent diagnostic strategies. Molecular genetics provide
      strong supportive information.

PMID- 15998674
TI  - Efferent vagal nerve stimulation protects heart against ischemia-induced
      arrhythmias by preserving connexin43 protein.
AB  - BACKGROUND: Myocardial ischemia (MI) leads to derangements in cellular electrical
      stability and the generation of lethal arrhythmias. Vagal nerve stimulation has
      been postulated to contribute to the antifibrillatory effect. Here, we suggest a
      novel mechanism for the antiarrhythmogenic properties of vagal stimulation during
      acute MI. METHODS AND RESULTS: Under anesthesia, Wistar rats underwent 30 minutes
      of left coronary artery (LCA) ligation with vagal stimulation (MI-VS group, n=11)
      and with sham stimulation (MI-SS group, n=12). Eight of the 12 rats in the MI-SS
      group had ventricular tachyarrhythmia (VT) during 30-minute LCA ligation; on the
      other hand, VT occurred in only 1 of the 11 rats in the MI-VS group (67% versus
      9%, respectively). Atropine administration abolished the antiarrhythmogenic
      effect of vagal stimulation. Immunoblotting revealed that the MI-SS group showed
      a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the
      MI-VS group showed only a slight reduction compared with the sham operation and
      sham stimulation group (37+/-20% versus 79+/-18%). Immunohistochemistry confirmed
      that the MI-induced loss of Cx43 from intercellular junctions was prevented by
      vagal stimulation. In addition, studies with rat primary-cultured cardiomyocytes
      demonstrated that acetylcholine effectively prevented the hypoxia-induced loss of
      phosphorylated Cx43 and ameliorated the loss of cell-to-cell communication as
      determined by Lucifer Yellow dye transfer assay, which supports the in vivo
      results. CONCLUSIONS: Vagal nerve stimulation exerts antiarrhythmogenic effects
      accompanied by prevention of the loss of phosphorylated Cx43 during acute MI and
      thus plays a critical role in improving ischemia-induced electrical instability.

PMID- 15998676
TI  - Metalloproteinase-2 and -9 in giant cell arteritis: involvement in vascular
      remodeling.
AB  - BACKGROUND: Both matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) have been
      postulated to play roles in the pathophysiology of giant cell arteritis (GCA)
      because of their ability to degrade elastin. Understanding the specific mediators
      of arterial damage in GCA could lead to new therapeutic targets in this disease.
      METHODS AND RESULTS: Temporal artery biopsy specimens were obtained from 147
      consecutive patients suspected of GCA. Clinical and histopathological data were
      collected according to protocol. Using immunohistochemistry, we compared the
      expression of MMP-2 and MMP-9 in the temporal artery biopsies of both GCA cases
      (n=50) and controls (n=97). MMP-9 was found more frequently in positive than in
      negative temporal artery biopsies (adjusted odds ratio [OR], 3.20; P=0.01). In
      contrast, the frequency of MMP-2 was not significantly different between positive
      and negative biopsies (adjusted OR, 2.18; P=0.22). Both MMP-2 and MMP-9 were
      found in macrophages and giant cells near the internal elastic lamina and in
      smooth muscle cells and myofibroblasts of the media and intima. MMP-9 was also
      found in the vasa vasorum. MMP-9 but not MMP-2 was associated with internal
      elastic lamina degeneration, intimal hyperplasia, and luminal narrowing, even
      after adjustment for possible confounding variables. CONCLUSIONS: MMP-9 appears
      more likely than MMP-2 to be involved in the pathophysiology of GCA. MMP-9 not
      only participates in the degradation of elastic tissue but also is associated
      with intimal hyperplasia, subsequent luminal narrowing, and neoangiogenesis. The
      expression of MMP by smooth muscle cells implicates these cells as potential
      secretory cells in GCA.

PMID- 15998677
TI  - Effect of pravastatin on rate of kidney function loss in people with or at risk
      for coronary disease.
AB  - BACKGROUND: Limited data suggest that HMG-CoA reductase inhibitors (statins)
      reduce rates of kidney function loss. We performed this analysis to determine
      whether pravastatin reduced the rate of kidney function loss over approximately 5
      years in people with or at high risk for coronary disease. METHODS AND RESULTS:
      This was a post hoc subgroup analysis of data from 3 randomized double-blind
      controlled trials comparing pravastatin 40 mg/d and placebo in subjects with a
      previous acute coronary syndrome or who were at high cardiovascular risk. The
      primary outcome was the rate of change in estimated glomerular filtration rate
      (GFR; in mL/min per 1.73 m2/y). The Modified Diet and Renal Disease Study (MDRD)
      and Cockcroft-Gault equations were used to estimate GFR. We studied 18,569
      participants, 3402 (18.3%) of whom had moderate chronic kidney disease as defined
      by an estimated GFR of 30 to 59.9 mL/min per 1.73 m2 body surface area. In
      subjects with moderate chronic kidney disease at baseline, pravastatin reduced
      the adjusted rate of kidney function loss by approximately 34%, although the
      absolute reduction in the rate of loss was small (0.22 mL/min per 1.73 m2/y by
      MDRD-GFR; 95% CI, 0.07 to 0.37). Pravastatin did not reduce the frequency of > or
      =25% decreases in kidney function in this group when MDRD-GFR was used to
      estimate GFR (relative risk [RR], 0.84; 95% CI, 0.66 to 1.06). When all 18,569
      subjects were considered, pravastatin reduced the adjusted rate of kidney
      function loss by 8% (0.08 mL/min per 1.73 m2/y by MDRD-GFR; 95% CI, 0.01 to 0.15)
      and the risk of acute renal failure (RR, 0.60; 95% CI, 0.41 to 0.86) but did not
      significantly reduce the frequency of a > or =25% decline in kidney function by
      MDRD-GFR (RR, 0.94; 95% CI, 0.88 to 1.01). CONCLUSIONS: Pravastatin modestly
      reduced the rate of kidney function loss in people with or at risk for
      cardiovascular disease. However, the primary indication for the use of statins in
      people with or at risk for coronary events remains the reduction in mortality
      that results from their use.

PMID- 15998678
TI  - Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with
      short-term costimulatory blockade to prevent cardiac allograft rejection.
AB  - BACKGROUND: The early inflammatory response during reperfusion of cardiac
      allografts is initiated by the infiltration of polymorphonuclear leukocytes
      (PMNs) into the graft. The impact of early PMN infiltration on allograft
      rejection compared with long-term graft survival remains poorly understood.
      METHODS AND RESULTS: We tested the role of CXCR2, the receptor for 2 PMN
      attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and
      vascularized cardiac allograft rejection in a murine model. Compared with
      allografts retrieved from control recipients, both PMN infiltration and
      intragraft proinflammatory cytokine expression were significantly attenuated in
      allografts from CXCR2-antisera-treated wild-type or from CXCR2(-/-) recipients.
      Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected
      allografts in control recipients, but T-cell infiltration was significantly
      decreased in recipients depleted of PMNs at transplantation. The influence of
      early PMN-mediated inflammation on the therapeutic efficacy of costimulatory
      blockade to prevent allograft rejection was tested. Short-term treatment of
      recipients with anti-CD154 mAb or CTLA-4 Ig induced modest prolongation of
      cardiac allograft survival. However, CD154 mAb or CTLA-4 Ig treatment, combined
      with either peritransplantation PMN depletion or antibodies specific for KC/CXCL1
      plus MIP-2/CXCL2, prolonged cardiac allograft survival beyond 100 days.
      CONCLUSIONS: Results suggest that strategies attenuating PMN-mediated tissue
      damage during reperfusion significantly improve the efficacy of short-term
      costimulatory blockade to prevent T-cell-mediated rejection of cardiac
      allografts.

PMID- 15998679
TI  - Mechanical unloading during left ventricular assist device support increases left
      ventricular collagen cross-linking and myocardial stiffness.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) induce reverse remodeling of
      the failing heart except for the extracellular matrix, which exhibits additional
      pathophysiological changes, although their mechanisms and functional consequences
      are unknown. METHODS AND RESULTS: Hearts were obtained at transplant from
      patients with idiopathic dilated cardiomyopathy (DCM) not requiring LVAD support
      (n=30), patients requiring LVAD support (n=16; LVAD duration, 145+/-33 days), and
      5 nonfailing hearts. Left (LV) and right ventricular (RV) ex vivo pressure-volume
      relationships were measured, and chamber and myocardial stiffness constants were
      determined. Myocardial tissue content of total and cross-linked collagen,
      collagen types I and III, MMP-1, MMP-9, TIMP-1, and angiotensin (Ang) I and II
      were measured. LV size, mass, and myocyte diameter decreased after LVAD compared
      with DCM without LVAD (P<0.05). Total and cross-linked collagen and ratio of type
      I to III collagen increased in DCM compared with nonfailing hearts and increased
      further after LVAD (P<0.05 versus DCM and nonfailing). Concomitantly, chamber and
      myocardial stiffness increased with LVAD. The ratio of MMP-1 to TIMP-1 increased
      in DCM and almost normalized after LVAD, favoring decreased collagen degradation.
      Tissue Ang I and II also increased during LVAD. There was no significant change
      in the RV of LVAD-supported heart compared with DCM. CONCLUSIONS: LVAD support
      increases LV collagen cross-linking and the ratio of collagen type I to III,
      which is associated with increased myocardial stiffness. Decreased tissue MMP-1
      to-TIMP-1 ratio (decreased degradation) and increased Ang levels (stimulants of
      synthesis) are likely mechanisms for these changes. Lack of significant effects
      on the RV suggest that hemodynamic unloading of the LV (not provided to the RV)
      might be the primary factor that regulates these extracellular matrix changes.

PMID- 15998680
TI  - Generic, simple risk stratification model for heart valve surgery.
AB  - BACKGROUND: Heart valve surgery has an associated in-hospital mortality rate of
      4% to 8%. This study aims to develop a simple risk model to predict the risk of
      in-hospital mortality for patients undergoing heart valve surgery to provide
      information to patients and clinicians and to facilitate institutional
      comparisons. METHODS AND RESULTS: Data on 32,839 patients were obtained from the
      Society of Cardiothoracic Surgeons of Great Britain and Ireland on patients who
      underwent heart valve surgery between April 1995 and March 2003. Data from the
      first 5 years (n=16,679) were used to develop the model; its performance was
      evaluated on the remaining data (n=16,160). The risk model presented here is
      based on the combined data. The overall in-hospital mortality was 6.4%. The risk
      model included, in order of importance (all P<0.01), operative priority, age,
      renal failure, operation sequence, ejection fraction, concomitant tricuspid valve
      surgery, type of valve operation, concomitant CABG surgery, body mass index,
      preoperative arrhythmias, diabetes, gender, and hypertension. The risk model
      exhibited good predictive ability (Hosmer-Lemeshow test, P=0.78) and
      discriminated between high- and low-risk patients reasonably well (receiver
      operating characteristics curve area, 0.77). CONCLUSIONS: This is the first risk
      model that predicts in-hospital mortality for aortic and/or mitral heart valve
      patients with or without concomitant CABG. Based on a large national database of
      heart valve patients, this model has been evaluated successfully on patients who
      had valve surgery during a subsequent time period. It is simple to use, includes
      routinely collected variables, and provides a useful tool for patient advice and
      institutional comparisons.

PMID- 15998681
TI  - Differential response of delayed healing and persistent inflammation at sites of
      overlapping sirolimus- or paclitaxel-eluting stents.
AB  - BACKGROUND: Although effective coverage of challenging coronary lesions has
      warranted the use of overlapping drug-eluting stents, the histopathological
      response to stent overlap is unknown. METHODS AND RESULTS: The arterial reaction
      to overlapping Cypher or Taxus drug-eluting stents was examined in rabbits with
      bare metal stents, BxVelocity or Express, serving as controls. Single iliac
      artery balloon injury was followed by placement of 2 overlapping 3.0-mm-diameter
      drug-eluting stents or bare metal stents in 60 animals (mean length of overlap,
      9.8+/-3.6 mm). Stented arteries were harvested at 28 and 90 days for histology.
      Overlapped segments exhibited delayed healing compared with proximal and distal
      nonoverlapping sites at 28 days. Overlapped segments in Taxus stents induced
      significantly more luminal heterophils/eosinophils and fibrin deposition than
      Cypher; peristrut giant cell infiltration, however, was more frequent in the
      latter. Overlapping bare metal stents also showed mild delayed healing compared
      with nonoverlapped segments, but not to the same extent as drug-eluting stents.
      Although neointimal thickness within the overlap was similar in 28- and 90-day
      Cypher stents, there was a significant increase with Taxus (P=0.03). CONCLUSIONS:
      Compared with bare metal stents, drug-eluting stents further delay arterial
      healing and promote inflammation at sites of overlap. Taxus stents induced
      greater fibrin deposition, medial cell loss, heterophils/eosinophils, and late
      neointimal hyperplasia. Patients receiving overlapping drug-eluting stents need
      more frequent follow-up than patients with nonoverlapping stents.

PMID- 15998682
TI  - Mapping of familial thoracic aortic aneurysm/dissection with patent ductus
      arteriosus to 16p12.2-p13.13.
AB  - BACKGROUND: Three loci have been shown to be responsible for nonsyndromic
      familial thoracic aortic aneurysms (TAAs) and aortic dissections (ADs). We
      recently described a large family in which TAA/AD associates with patent ductus
      arteriosus (PDA) and provided genetic arguments for a unique pathophysiological
      entity. METHODS AND RESULTS: Genome-wide scan was performed in 40 subjects
      belonging to 3 generations in this large pedigree. Using the 7 TAA/AD cases as
      affected, we observed positive 2-point LOD scores on adjacent markers at
      chromosome 16p, with a maximum LOD score value of 2.73 at theta=0, a value that
      increased to 3.56 when 5 PDA cases were included. Multipoint linkage analysis
      yielded a maximum LOD score of 4.14 in the vicinity of marker D16S3103. Fine
      mapping allowed the observation of recombinant haplotypes that delimited a
      critical 20-cM interval at 16p12.2-p13.13. Automatic determination of aortic
      compliance with cine MRI showed that all subjects bearing the disease haplotype,
      even asymptomatic, displayed a very low level of aortic compliance and
      distensibility. Aortic stiffness was strongly associated with disease haplotype
      with a marked effect of age, indicating subclinical and early manifestation of
      the disease. CONCLUSIONS: Genetic analysis of this family identified a unique
      locus responsible for both TAA/AD and PDA at chromosome 16p12.2-p13.13 with
      aortic stiffness as an early hallmark of the disease. TAA/AD with PDA is a new
      monogenic entity among the genetically heterogeneous group of TAA/AD disease.

PMID- 15998683
TI  - Organization of myocardial activation during ventricular fibrillation after
      myocardial infarction: evidence for sustained high-frequency sources.
AB  - BACKGROUND: Studies of ventricular fibrillation (VF) in small mammals have
      revealed localized sustained stationary reentry. However, studies in large
      mammals with surface mapping techniques have demonstrated only relatively short
      lived rotors. The purpose of this study was to identify whether sustained high
      frequency activation with low beat-to-beat variability was present at intramural
      sites in a postinfarct ovine model of VF. METHODS AND RESULTS: VF was induced in
      12 sheep 77+/-40 days after anterior myocardial infarction. Electrical activation
      was recorded with 20 multielectrode transmural plunge needles. Unipolar
      electrogram frequency content and local cycle duration variability were studied
      in 30-second recordings beginning 5 seconds after the onset of VF. Higher mean
      beat frequency was associated with lower SD of the cycle duration intervals (r=
      0.91, P<0.001). The mean beat frequency and the SD of cycle duration intervals of
      the highest-frequency electrode were 8.8+/-2.0 Hz and 17+/-11 ms. In 3 cases, a
      region with regular activation throughout the recording was identified (SD of the
      cycle duration interval, 6.0+/-0.7 ms). Two of these sites and 67% of all sites
      with low local cycle duration variability were intramural. They occurred within
      regions with a high dominant frequency as determined by fast Fourier transform of
      the unipolar electrogram. CONCLUSIONS: Regions with the highest frequency of
      activation during VF were always associated with a low local cycle duration
      variability and usually intramural in this chronic infarct model. In a minority
      of cases, a region of stable, rapid, and very regular activation could be
      identified. These findings support the hypothesis that relatively stable periodic
      sources form a component of the mechanism of VF in this model.

PMID- 15998684
TI  - Glucose-6 phosphate dehydrogenase deficiency decreases the vascular response to
      angiotensin II.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) regulates production of the
      reduced form of NADPH through the pentose phosphate pathway. G6PD may therefore
      affect superoxide anion production via vascular NADPH oxidase, which is key in
      mediating the vascular response to angiotensin II (Ang II). We determined the
      hypertensive and vascular hypertrophic response to Ang II in G6PD-deficient mice.
      METHODS AND RESULTS: Ang II (0.7 mg/kg per day) was infused via subcutaneous
      osmotic pumps for 6 days in male hemizygote G6PD mutant (G6PD(mut)) and wild-type
      (WT) C3H mice. (1) Compared with WT, G6PD(mut) mouse aorta had 10% to 20% of G6PD
      activity and 50% less NADPH. (2) Basal systolic blood pressure was not
      significantly different in G6PD(mut) mice (WT 88+/-4 mm Hg versus G6PD(mut) 95+/
      4 mm Hg), but Ang II increased blood pressure to a lower level in G6PD(mut) mice
      (WT 139+/-4 mm Hg versus G6PD(mut) 123+/-5 mm Hg; P<0.05). (3) Ang II increased
      aortic medial thickness less in G6PD(mut) mice (WT 71+/-2 mum versus G6PD(mut)
      62+/-1 mum; P<0.01). (4) 3-o-Nitrotyrosine staining and dihydroethidium oxidation
      in the aorta was increased by Ang II less in G6PD(mut) mice. (5) Smooth muscle
      cells isolated from G6PD(mut) mice showed less Ang II-induced phosphorylation of
      Akt and p42/44 ERK. CONCLUSIONS: G6PD deficiency may reduce vascular superoxide
      anion production by limiting production of the substrate for NADPH oxidase,
      thereby inhibiting oxidant-mediated Ang II-induced signaling pathways that
      contribute to hypertension and smooth muscle hypertrophy.

PMID- 15998685
TI  - Hereditary hemochromatosis and risk of ischemic heart disease: a prospective
      study and a case-control study.
AB  - BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis
      genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for
      ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS:
      We performed a prospective study of 9178 individuals from the Danish general
      population followed up for 24 years, during which 1035 and 511 developed IHD and
      MI, respectively, and a case-control study of 2441 and 1113 IHD and MI cases
      versus 8080 controls. C282Y/C282Y, C282Y/H63D, and C282Y/wild-type versus wild
      type/wild-type individuals were not associated with increased risk of IHD or MI
      in prospective studies, overall or stratified by gender. We had 90% power to
      detect a hazard ratio for IHD of 3.4 for C282Y/C282Y, 1.9 for C282Y/H63D, and 1.3
      for C282Y/wild-type versus wild-type/wild-type. Furthermore, these genotypes were
      not associated with increased risk of IHD or MI in case-control studies, overall
      or stratified by gender. We had 90% power to detect an odds ratio for IHD of 3.6
      for C282Y/C282Y, 1.8 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild
      type/wild-type. CONCLUSIONS: In these studies, hereditary hemochromatosis
      C282Y/C282Y, C282Y/H63D, and C282Y/wild-type genotypes were not associated with
      IHD or MI; however, the study lacked the power to exclude the possibility that
      C282Y/C282Y and C282Y/H63D individuals have a modestly increased risk of IHD or
      MI.

PMID- 15998686
TI  - Images in cardiovascular medicine. Detection of luminal-intimal border and
      coronary wall enhancement in intravascular ultrasound imaging after injection of
      microbubbles and simultaneous sonication with transthoracic echocardiography.

PMID- 15998687
TI  - Letter regarding article by Galbreath et al, "Long-term healthcare and cost
      outcomes of disease management in a large, randomized, community-based population
      with heart failure".

PMID- 15998688
TI  - Images in cardiovascular medicine. Detection of carotid atherosclerotic plaque
      ulceration, calcification, and thrombosis by multicontrast weighted magnetic
      resonance imaging.

PMID- 15998689
TI  - Images in cardiovascular medicine. Primary lymphoma of the heart.

PMID- 15998690
TI  - Letter regarding article by McNair et al, "SCN5A mutation associated with dilated
      cardiomyopathy, conduction disorder, and arrhythmia".

PMID- 15998692
TI  - Endothelial progenitor cells, neointimal hyperplasia, and hemodialysis vascular
      access dysfunction: novel therapies for a recalcitrant clinical problem.

PMID- 15998693
TI  - Cell death and adenosine triphosphate: the paradox.

PMID- 15998694
TI  - N-terminal-pro-B-type natriuretic peptide: universal marker of cardiovascular
      risk?

PMID- 15998695
TI  - Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and
      hypertrophic phenotypes of cardiomyopathy.
AB  - BACKGROUND: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause
      hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human
      hearts, downregulation of alphaMyHC mRNA or protein has been correlated with
      systolic dysfunction. We hypothesized that mutations in alphaMyHC could also lead
      to pleiotropic cardiac phenotypes, including HCM and DCM. METHODS AND RESULTS: A
      cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging
      to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM
      families, was screened for alphaMyHC gene (MYH6) mutations. Three heterozygous
      MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and
      E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands
      and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in
      highly conserved residues, were predicted to change the structure or chemical
      bonds of alphaMyHC, and were absent in at least 300 control chromosomes from an
      ethnically similar population. The DCM carrier phenotype was characterized by
      late onset, whereas the HCM phenotype was characterized by progression toward
      dilation, left ventricular dysfunction, and refractory heart failure.
      CONCLUSIONS: This study suggests that mutations in MYH6 may cause a spectrum of
      phenotypes ranging from DCM to HCM.

PMID- 15998696
TI  - Statin treatment after onset of sepsis in a murine model improves survival.
AB  - BACKGROUND: HMG-CoA-reductase inhibitors have been shown to exhibit pronounced
      immunomodulatory effects independent of lipid lowering. We have recently
      demonstrated that pretreatment with simvastatin profoundly improves survival in a
      cecal ligation and perforation (CLP) model of sepsis. Here, we studied whether
      treatment with simvastatin after onset of sepsis-induced hemodynamic alterations
      is beneficial and whether prolonged survival can also be achieved with other
      statins. METHODS AND RESULTS: Mice were rendered septic by CLP. At 6 hours after
      sepsis induction, when profound hemodynamic alterations were manifest, treatment
      with atorvastatin, fluvastatin, pravastatin, simvastatin, or placebo was
      initiated. Except for fluvastatin (27+/-2.3 hours), survival time was extended
      from 23+/-1.2 hours for placebo-treated mice to 37+/-3.6 hours for simvastatin
      treated, to 40+/-4.2 hours for atorvastatin-treated, and to 39+/-3.9 hours for
      pravastatin-treated mice. This profound improvement is based on the preservation
      of cardiac function and hemodynamic status in statin-treated animals, both of
      which are severely impaired in untreated CLP mice. As underlying mechanisms,
      improved susceptibility to endothelial nitric oxide synthase stimulation and
      reduced endothelial adhesion of leukocytes could be demonstrated after statin
      treatment. CONCLUSIONS: Well established in the treatment of lipid disorders and
      coronary artery disease, statins harbor the additional and novel potential of
      effective sepsis treatment. This benefit extends to several but not all statins
      tested.

PMID- 15998697
TI  - Valvular heart disease: aortic regurgitation.
AB  - Aortic regurgitation (AR) is characterized by diastolic reflux of blood from the
      aorta into the left ventricle (LV). Acute AR typically causes severe pulmonary
      edema and hypotension and is a surgical emergency. Chronic severe AR causes
      combined LV volume and pressure overload. It is accompanied by systolic
      hypertension and wide pulse pressure, which account for peripheral physical
      findings, such as bounding pulses. The afterload excess caused by systolic
      hypertension leads to progressive LV dilation and systolic dysfunction. The most
      important diagnostic test for AR is echocardiography. It provides the ability to
      determine the cause of AR and to assess the severity of AR and its effect on LV
      size, function, and hemodynamics. Many patients with chronic severe AR may remain
      clinically compensated for years with normal LV function and no symptoms. These
      patients do not require surgery but can be followed carefully for the onset of
      symptoms or LV dilation/dysfunction. Surgery should be considered before the LV
      ejection fraction falls below 55% or the LV end-systolic [corrected] dimension
      reaches 55 mm. Symptomatic patients should undergo surgery unless there are
      excessive comorbidities or other contraindications. The primary role of medical
      therapy with vasodilators is to delay the need for surgery in asymptomatic
      patients with normal LV function or to treat patients in whom surgery is not an
      option. The goal of vasodilator therapy is to achieve a significant decrease in
      systolic arterial pressure. Future therapies may focus on molecular mechanisms to
      prevent adverse LV remodeling and fibrosis.

PMID- 15998698
TI  - Frontiers in cardiovascular magnetic resonance.

PMID- 15998699
TI  - A vision for the future: opportunities and challenges: notes from the director of
      the National Heart, Lung, and Blood Institute.

PMID- 15998700
TI  - Unconventional homologous internalization of the angiotensin II type-1 receptor
      induced by G-protein-independent signals.
AB  - Internalization of a G-protein-coupled receptor (GPCR) is essential to the
      desensitization, endocytosis, and signal transduction of the receptor. It has
      been the general view that conventional homologous internalization of a GPCR
      requires activation of the G-protein(s) coupled to the receptor. However, whether
      and how GPCR-mediated G-protein-independent signals trigger receptor
      internalization remains unknown, although G-protein-independent internalization
      has been reported. Here we show that an angiotensin II (Ang II) type-1 (AT1)
      receptor mutant incapable of activating any G-protein still undergoes normal
      internalization. Substitution of Asp125 with Ala and Arg126 with Leu at the
      highly conserved DRY motif of the AT1 receptor disabled the ability of the
      receptor to activate G-proteins, as shown by various Ang II binding studies, GDP
      GTP exchange, and inositol phosphate production assays. Surprisingly, the mutant
      internalized normally in the presence of Ang II and transactivated the epidermal
      growth factor receptor (EGFR). Similar to the wild-type receptor, overexpression
      of a dominant-negative K220R mutant GRK2 diminished the internalization of D125A
      R126L but not the transactivation of EGFR. These data indicate that G-protein
      independent specific signals may also trigger homologous internalizations of the
      AT1 receptor through beta-arrestin-dependent and -independent pathways,
      suggesting a possible mechanism for G-protein-independent activation of G-protein
      coupled receptor kinases (GRKs). This may represent a general mechanism for
      triggering GPCR internalization.

PMID- 15998702
TI  - Comparison of blood pressure-associated risk of intracerebral hemorrhage and
      subarachnoid hemorrhage: Korea Medical Insurance Corporation study.
AB  - Intracerebral hemorrhage and subarachnoid hemorrhage have different pathogeneses
      and risk factor profiles. However, little information is available on the
      difference between intracerebral and subarachnoid hemorrhages in relation to
      blood pressure. We prospectively investigated the relationships between blood
      pressure and risks of stroke subtypes. We measured blood pressure and other
      cardiovascular risk factors in 100,147 men and 59,558 women 35 to 59 years of age
      in 1990 and 1992. Outcomes were fatal and nonfatal events of stroke and its
      subtypes from 1993 to 2002. Independent relationships between baseline blood
      pressure and stroke subtypes were assessed using Cox's proportional hazard
      models. During the 10 years, 1714 ischemic and 1159 hemorrhagic strokes (742
      intracerebral and 308 subarachnoid hemorrhages) occurred. Blood pressure was
      related more closely with hemorrhagic stroke than ischemic stroke, and the
      difference was more prominent in women. Among the subtypes of hemorrhagic stroke,
      intracerebral hemorrhage was more closely related with blood pressure than
      subarachnoid hemorrhage. For each 20 mm Hg increase in systolic blood pressure,
      adjusted relative risks of ischemic stroke, intracerebral hemorrhage, and
      subarachnoid hemorrhage were 1.79 (95% confidence interval, 1.68 to 1.90), 2.48
      (2.30 to 2.68), and 1.65 (1.38 to 1.97) in men, and 1.64 (1.42 to 1.89), 3.15
      (2.61 to 3.80), and 2.29 (1.82 to 2.89) in women, respectively. In conclusion,
      blood pressure is more closely related with intracerebral hemorrhage than
      subarachnoid hemorrhage, thus proportion of intracerebral hemorrhage in
      hemorrhagic stroke may affect the association between blood pressure and
      hemorrhagic stroke. Our data also emphasize the importance of blood pressure
      control for the prevention of stroke, especially in countries with a high
      incidence of intracerebral hemorrhage.

PMID- 15998703
TI  - Growing old, angiotensin II, cardiac hypertrophy, and death: making the
      connection with p66Shc.

PMID- 15998704
TI  - Genetic deletion of the p66Shc adaptor protein protects from angiotensin II
      induced myocardial damage.
AB  - Angiotensin II (Ang II), acting through its G protein-coupled AT1 receptor (AT1),
      contributes to the precocious heart senescence typical of patients with
      hypertension, atherosclerosis, and diabetes. AT1 was suggested to transactivate
      an intracellular signaling controlled by growth factors and their tyrosin-kinase
      receptors. In cultured vascular smooth muscle cells, this downstream mechanism
      comprises the p66Shc adaptor protein, previously recognized to play a role in
      vascular cell senescence and death. The aim of the present study was 2-fold: (1)
      to characterize the cardiovascular phenotype of p66Shc knockout mice (p66Shc(-/
      )), and (2) to test the novel hypothesis that disrupting the p66Shc might protect
      the heart from the damaging action of elevated Ang II levels. Compared with wild
      type littermates (p66Shc(+/+)), p66Shc(-/-) showed similar blood pressure, heart
      rate, and left ventricular wall thickness. However, cardiomyocyte number was
      increased in mutant animals, indicating a condition of myocardial hyperplasia. In
      p66Shc(+/+), infusion of a sub-pressor dose of Ang II (300 nmol/kg body weight
      [BW] daily for 28 days) caused left ventricular hypertrophy and apoptotic death
      of cardiomyocytes and endothelial cells. In contrast, p66Shc(-/-) were resistant
      to the proapoptotic/hypertrophic action of Ang II. Consistently, in vitro
      experiments showed that Ang II causes apoptotic death of cardiomyocytes isolated
      from p66Shc(+/+) hearts to a greater extent as compared with p66Shc(-/-)
      cardiomyocytes. Our results indicate a fundamental role of p66Shc in Ang II
      mediated myocardial remodeling. In perspective, p66Shc inhibition may be
      envisioned as a novel way to prevent the deleterious effects of Ang II on the
      heart.

PMID- 15998705
TI  - With-no-lysine kinases: the discovery of a new pathway in hypertension using
      human genetic studies.

PMID- 15998706
TI  - Differing effects of mineralocorticoid receptor-dependent and -independent
      potassium-sparing diuretics on fibrinolytic balance.
AB  - This study tests the hypothesis that spironolactone influences plasminogen
      activator inhibitor-1 (PAI-1) concentrations through mineralocorticoid receptor
      antagonism rather than through changes in potassium. Effects of spironolactone
      (50 mg per day) and triamterene (50 mg per day) on fibrinolytic balance were
      compared in 18 normotensive and 20 hypertensive subjects pretreated with
      hydrochlorothiazide (HCTZ; 12.5 mg per day). Blood pressure and serum potassium
      were similar in spironolactone and triamterene treatment groups. The effect of
      the 2 drugs on the renin-angiotensin-aldosterone system was also similar. In
      contrast, spironolactone and triamterene exerted opposing effects on PAI-1
      antigen (P=0.006 for drug effect). In normotensive subjects, triamterene (from
      10.1+/-7.8 to 16.9+/-9.9 ng/mL at 9 am, P=0.019; from 7.6+/-5.4 to 11.5+/-7.3
      ng/mL at 11 am, P=0.027; from 9.3+/-7.7 to 13.7+/-8.5 ng/mL for average of all
      time points, P=0.054) but not spironolactone significantly increased PAI-1
      antigen. In hypertensive subjects, spironolactone significantly decreased PAI-1
      antigen (from 22.0+/-23.4 to 16.7+/-19.0 ng/mL at 10 am, P=0.041; from 17.5+/
      21.7 to 12.7+/-16.8 ng/mL at 11 am, P=0.043; from 20.3+/-22.6 to 16.6+/-19.7
      ng/mL for average of all time points, P=0.014), whereas there was no effect of
      triamterene. Only spironolactone significantly decreased the molar ratio of PAI-1
      to tissue-type plasminogen activator (t-PA) in hypertensive subjects. By
      regression analysis, predictors of mean PAI-1 response were spironolactone versus
      triamterene (P=0.014), hypertension (P=0.002), and PAI-1 response to HCTZ
      (P=0.019), with a trend for aldosterone (P=0.061). Mineralocorticoid receptor
      antagonism prevents the effect of activation of the renin-angiotensin-aldosterone
      system on PAI-1 antigen in normotensive subjects and improves fibrinolytic
      balance in hypertensive subjects through a potassium-independent mechanism.

PMID- 15998707
TI  - A new kindred with pseudohypoaldosteronism type II and a novel mutation (564D>H)
      in the acidic motif of the WNK4 gene.
AB  - We identified a new kindred with the familial syndrome of hypertension and
      hyperkalemia (pseudohypoaldosteronism type II or Gordon's syndrome) containing an
      affected father and son. Mutation analysis confirmed a single heterozygous G to C
      substitution within exon 7 (1690G>C) that causes a missense mutation within the
      acidic motif of WNK4 (564D>H). We confirmed the function of this novel mutation
      by coexpressing it in Xenopus oocytes with either the NaCl cotransporter (NCCT)
      or the inwardly rectifying K-channel (ROMK). Wild-type WNK4 inhibits 22Na+ flux
      in Xenopus oocytes expressing NCCT by approximately 90% (P<0.001), whereas the
      564D>H mutant had no significantly inhibitory effect on flux through NCCT. In
      oocytes expressing ROMK, wild-type WNK4 produced >50% inhibition of steady-state
      current through ROMK at a +20-mV holding potential (P<0.001). The 564D>H mutant
      produced further inhibition with steady-state currents to some 60% to 70% of
      those seen with the wild-type WNK4. Using fluorescent-tagged NCCT (enhanced cyan
      fluorescent protein-NCCT) and ROMK (enhanced green fluorescent protein-ROMK) to
      quantify the expression of the proteins in the oocyte membrane, it appears that
      the functional effects of the 564D>H mutation can be explained by alteration in
      the surface expression of NCCT and ROMK. Compared with wild-type WNK4, WNK4
      564D>H causes increased cell surface expression of NCCT but reduced expression of
      ROMK. This work confirms that the novel missense mutation in WNK4, 564D>H, is
      functionally active and highlights further how switching charge on a single
      residue in the acid motif of WNK4 affects its interaction with the thiazide
      sensitive target NCCT and the potassium channel ROMK.

PMID- 15998708
TI  - North American ginseng exerts a neutral effect on blood pressure in individuals
      with hypertension.
AB  - An early observational study suggested that ginseng could elevate blood pressure.
      This caused concern because 4.5% of American adults use ginseng, with a popular
      choice being North American ginseng. To date, North American ginseng lacks
      hemodynamic evaluation; therefore, we conducted a randomized, double-blinded,
      controlled trial to investigate its effect on blood pressure in 16 hypertensive
      individuals (mean+/-SD age 61.1+/-8.1 years; systolic/diastolic blood pressure
      132.4+/-12.8/83.3+/-8.1 mm Hg; 13 on antihypertensives). We used 6 batches of
      North American ginseng root that varied in quality and ginsenoside content,
      representing the spectrum of this ginseng on the market. On 8 mornings, each
      participant was fitted with an ambulatory blood pressure monitor, which measured
      blood pressure during a 30-minute baseline period. Each participant then consumed
      in a randomized and double-blind fashion 3 g of encapsulated treatment: placebo
      (on 2 mornings) or powdered North American ginseng (on 6 mornings). After
      treatment, blood pressure was measured every 10 minutes for 160 minutes, and its
      change at each post-treatment time point relative to baseline was determined per
      individual and averaged, and the mean was obtained for the overall 160-minute
      period. None of the North American ginsengs or their mean differed from placebo
      in their effect on overall (160 minutes) mean blood pressure change. None
      affected blood pressure versus placebo at the 10-minute intervals; but their mean
      versus placebo increased systolic and diastolic blood pressure at 140 and 160
      minutes, respectively, and lowered diastolic blood pressure at 100 minutes. The
      findings together suggested that North American ginseng exerts a neutral acute
      effect on blood pressure in hypertensive individuals.

PMID- 15998709
TI  - The many possible benefits of natriuretic peptides after myocardial infarction.

PMID- 15998710
TI  - Electrophysiological properties of rostral ventrolateral medulla neurons in
      angiotensin II 1a receptor knockout mice.
AB  - We compared the electrophysiological properties of neurons in the rostral
      ventrolateral medulla of neonatal angiotensin II type 1a receptor knockout mice
      and wild-type mice with responses to angiotensin II, its type-1 receptor blocker
      candesartan, and its type-2 receptor blocker PD123319. Using the whole-cell patch
      clamp technique, we examined the characteristics of rostral ventrolateral medulla
      neurons in brain stem-spinal cord preparations in which the sympathetic neuronal
      network is preserved. Baseline membrane potential and firing rate were almost
      similar between angiotensin II type 1a receptor knockout mice and wild-type mice.
      Superfusion with angiotensin II depolarized rostral ventrolateral medulla
      bulbospinal neurons in wild-type mice, whereas it hyperpolarized those in
      angiotensin II type 1a receptor knockout mice. Because pretreatment with
      candesartan significantly prevented the angiotensin II-induced depolarization in
      wild-type mice, the angiotensin II type 1 receptor is crucial for this
      depolarization. Superfusion with PD123319 depolarized rostral ventrolateral
      medulla bulbospinal neurons in angiotensin II type 1a receptor knockout mice.
      PD123319 prevented the angiotensin II-induced hyperpolarization in angiotensin II
      type 1a receptor knockout mice, and, rather, it induced depolarization. These
      results suggest that the angiotensin II type 2 receptor in rostral ventrolateral
      medulla plays an antagonistic role against the angiotensin II type 1a receptor in
      controlling the neuronal activity of rostral ventrolateral medulla.

PMID- 15998711
TI  - Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction
      evaluated using genetically engineered mice.
AB  - Although plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic
      peptide (BNP) are elevated early after myocardial infarction (MI), the
      significance is not fully understood. We therefore investigated the function of
      natriuretic peptides after induction of MI in knockout (KO) mice lacking the
      natriuretic peptide receptor guanylyl cyclase-A, the receptor for ANP and BNP. KO
      and wild-type (WT) mice were subjected to left coronary artery ligation and then
      followed up for 4 weeks. Irrespective of genotype, almost all deaths occurred
      within 1 week after induction of MI. KO mice showed significantly higher
      mortality because of a higher incidence of acute heart failure, which was
      associated with diminished water and sodium excretion and with higher cardiac
      levels of mRNAs encoding ANP, BNP, transforming growth factor-beta1, and type I
      collagen. By 4 weeks after infarction, left ventricular remodeling, including
      myocardial hypertrophy and fibrosis, and impairment of left ventricular systolic
      function were significantly more severe in KO than WT mice. Notably, the enhanced
      myocardial fibrosis seen in KO mice was virtually absent in infarcted double-KO
      mice, lacking guanylyl cyclase-A and angiotensin II type 1a receptors, although
      there was no improvement in survival and no attenuation of cardiac hypertrophy.
      Thus, guanylyl cyclase-A activation by endogenous cardiac natriuretic peptides
      protects against acute heart failure and attenuates chronic cardiac remodeling
      after MI. These beneficial effects are mediated partly through inhibition of the
      renin-angiotensin system (RAS), although RAS-independent protective actions of
      guanylyl cyclase-A are also suggested.

PMID- 15998712
TI  - Angiotensin II-mediated phenotypic cardiomyocyte remodeling leads to age
      dependent cardiac dysfunction and failure.
AB  - Chronic elevation of plasma angiotensin II (Ang II) is detrimental to the heart.
      In addition to its hemodynamic effects, Ang II exerts cardiotrophic actions that
      contribute to cardiomyocyte remodeling. However, it remains to be clarified
      whether these direct actions of Ang II are sufficient to cause contractile
      dysfunction and heart failure in the absence of altered hemodynamic conditions.
      In this study, we used TG1306/1R (TG) mice that develop Ang II-mediated cardiac
      hypertrophy in absence of elevated blood pressure to investigate the phenotypic
      changes in cardiomyocytes during the adaptive response to chronic cardiac
      specific endogenous Ang II stimulation. A 94-week longitudinal study demonstrated
      that TG mice develop dilated cardiomyopathy with aging and exhibit a significant
      increase in mortality compared with wild-type (WT) mice. Cardiac hypertrophy in
      TG mice is associated with cardiomyocyte hypertrophy (15 to 20 weeks: length
      +20%; 35 to 40 weeks: length +10%, width +15%) but not collagen deposition. In
      vivo analysis of cardiac function revealed age-dependent systolic and diastolic
      dysfunction in TG mice (approximately 45% reduction in dP/dtmax and dP/dtmin at
      50 to 60 weeks of age compared with WT). Analysis of isolated cardiomyocyte
      isotonic shortening showed impaired contractility in TG cardiomyocytes (30% to
      40% decrease in rates of shortening and lengthening). In TG hearts, chronic Ang
      II exposure induced downregulation of the sarcoplasmic reticulum calcium pump
      (SERCA2) and diminution of Ca2+ transients, indicative of an underlying
      disturbance in calcium homeostasis. In conclusion, chronic Ang II myocardial
      stimulation without hemodynamic overload is sufficient to produce cardiomyocyte
      and cardiac dysfunction culminating in heart failure.

PMID- 15998713
TI  - Noncardiovascular illness as barrier to antihypertensive treatment.

PMID- 15998714
TI  - Transcriptional compensation for gene loss plays a minor role in maintaining
      genetic robustness in Saccharomyces cerevisiae.
AB  - If a gene is mutated and its function lost, are compensatory genes upregulated?
      We investigated whether genes are transcriptionally upregulated when their
      synthetic sick or lethal (SSL) partners are lost. We identified several new
      examples; however, remarkably few SSL pairs exhibited this phenomenon, suggesting
      that transcriptional compensation by SSL partners is a rare mechanism for
      maintaining genetic robustness.

PMID- 15998715
TI  - Genome-wide synthetic lethal screens identify an interaction between the nuclear
      envelope protein, Apq12p, and the kinetochore in Saccharomyces cerevisiae.
AB  - The maintenance of genome stability is a fundamental requirement for normal cell
      cycle progression. The budding yeast Saccharomyces cerevisiae is an excellent
      model to study chromosome maintenance due to its well-defined centromere and
      kinetochore, the region of the chromosome and associated protein complex,
      respectively, that link chromosomes to microtubules. To identify genes that are
      linked to chromosome stability, we performed genome-wide synthetic lethal screens
      using a series of novel temperature-sensitive mutations in genes encoding a
      central and outer kinetochore protein. By performing the screens using different
      mutant alleles of each gene, we aimed to identify genetic interactions that
      revealed diverse pathways affecting chromosome stability. Our study, which is the
      first example of genome-wide synthetic lethal screening with multiple alleles of
      a single gene, demonstrates that functionally distinct mutants uncover different
      cellular processes required for chromosome maintenance. Two of our screens
      identified APQ12, which encodes a nuclear envelope protein that is required for
      proper nucleocytoplasmic transport of mRNA. We find that apq12 mutants are
      delayed in anaphase, rereplicate their DNA, and rebud prior to completion of
      cytokinesis, suggesting a defect in controlling mitotic progression. Our analysis
      reveals a novel relationship between nucleocytoplasmic transport and chromosome
      stability.

PMID- 15998716
TI  - Two quantitative trait loci for prepulse inhibition of startle identified on
      mouse chromosome 16 using chromosome substitution strains.
AB  - Prepulse inhibition (PPI) of acoustic startle is a genetically complex
      quantitative phenotype of considerable medical interest due to its impairment in
      psychiatric disorders such as schizophrenia. To identify quantitative trait loci
      (QTL) involved in mouse PPI, we studied mouse chromosome substitution strains
      (CSS) that each carry a homologous chromosome pair from the A/J inbred strain on
      a host C57BL/6J inbred strain background. We determined that the chromosome 16
      substitution strain has elevated PPI compared to C57BL/6J (P = 1.6 x 10(-11)),
      indicating that chromosome 16 carries one or more PPI genes. QTL mapping using 87
      F(2) intercross progeny identified two significant chromosome 16 loci with LODs
      of 3.9 and 4.7 (significance threshold LOD is 2.3). The QTL were each highly
      significant independently and do not appear to interact. Sequence variation
      between B6 and A/J was used to identify strong candidate genes in the QTL
      regions, some of which have known neuronal functions. In conclusion, we used
      mouse CSS to rapidly and efficiently identify two significant QTL for PPI on
      mouse chromosome 16. The regions contain a limited number of strong biological
      candidate genes that are potential risk genes for psychiatric disorders in which
      patients have PPI impairments.

PMID- 15998717
TI  - A genetic screen identifies putative targets and binding partners of CREB-binding
      protein in the developing Drosophila eye.
AB  - Drosophila CREB-binding protein (dCBP) is a very large multidomain protein, which
      belongs to the CBP/p300 family of proteins that were first identified by their
      ability to bind the CREB transcription factor and the adenoviral protein E1.
      Since then CBP has been shown to bind to >100 additional proteins and functions
      in a multitude of different developmental contexts. Among other activities, CBP
      is known to influence development by remodeling chromatin, by serving as a
      transcriptional coactivator, and by interacting with terminal members of several
      signaling transduction cascades. Reductions in CBP activity are the underlying
      cause of Rubinstein-Taybi syndrome, which is, in part, characterized by several
      eye defects, including strabismus, cataracts, juvenile glaucoma, and coloboma of
      the eyelid, iris, and lens. Development of the Drosophila melanogaster compound
      eye is also inhibited in flies that are mutant for CBP. However, the vast array
      of putative protein interactions and the wide-ranging roles played by CBP within
      a single tissue such as the retina can often complicate the analysis of CBP loss
      of-function mutants. Through a series of genetic screens we have identified
      several genes that could either serve as downstream transcriptional targets or
      encode for potential CBP-binding partners and whose association with eye
      development has hitherto been unknown. The identification of these new components
      may provide new insight into the roles that CBP plays in retinal development. Of
      particular interest is the identification that the CREB transcription factor
      appears to function with CBP at multiple stages of retinal development.

PMID- 15998718
TI  - Cost of interacting with sexual partners in a facultative sexual microbe.
AB  - The widespread occurrence of sexual organisms despite the high costs of sex has
      long intrigued biologists. The best-known costs are the twofold cost of producing
      males and the cost associated with producing traits to attract mates and to
      interact with mating partners, such as exaggerated sexual behaviors and
      morphological modifications. These costs have been inferred from studies of
      plants and animals but are thought to be absent in facultative sexual microbes.
      Here, using the facultative sexual fungus Cryptococcus neoformans, I provide
      experimental evidence showing that: (i) interactions with active sexual partners
      can be costly for vegetative fitness in a facultative sexual microbe; (ii) this
      cost is positively correlated to mating ability; (iii) this cost is composed of
      at least two distinct components, the cost of producing mating signals that exert
      effects on mating partners and that associated with responding to active mating
      partners; and (iv) extended asexual reproduction can reduce both components of
      the cost. This cost must have been compensated for by the production of zygotes
      and sexual spores to allow the initial evolution and spread of sexual
      reproduction in eukaryotes.

PMID- 15998719
TI  - Mutational hypersensitivity of a gene regulatory protein: Saccharomyces
      cerevisiae Gal80p.
AB  - The inhibitor of galactose catabolic (GAL) gene expression in Saccharomyces
      cerevisiae, Gal80p, interacts with the activator Gal4p and the signal transducer
      Gal3p and self-associates. Selection for loss of Gal80p inhibitor function
      yielded gal80 mutants at an extremely high rate. Out of these, 21 nonoverlapping
      point mutants were identified; each were due to a single-amino-acid exchange in
      conserved residues. Semiquantitative biochemical analysis of the corresponding
      mutant proteins revealed that each of the 21 amino acid alterations caused
      simultaneous defects in every single protein-protein interaction and in Gal80's
      structural integrity. Thus, Gal80 provides an unprecedented example for a
      protein's structural sensitivity to minimal sequence alterations.

PMID- 15998720
TI  - A genetic screen for dominant modifiers of a small-wing phenotype in Drosophila
      melanogaster identifies proteins involved in splicing and translation.
AB  - Studies in the fly, Drosophila melanogaster, have revealed that several signaling
      pathways are important for the regulation of growth. Among these, the insulin
      receptor/phosphoinositide 3-kinase (PI3K) pathway is remarkable in that it
      affects growth and final size without disturbing pattern formation. We have used
      a small-wing phenotype, generated by misexpression of kinase-dead PI3K, to screen
      for novel mutations that specifically disrupt organ growth in vivo. We identified
      several complementation groups that dominantly enhance this small-wing phenotype.
      Meiotic recombination in conjunction with visible markers and single-nucleotide
      polymorphisms (SNPs) was used to map five enhancers to single genes. Two of
      these, nucampholin and prp8, encode pre-mRNA splicing factors. The three other
      enhancers encode factors required for mRNA translation: pixie encodes the
      Drosophila ortholog of yeast RLI1, and RpL5 and RpL38 encode proteins of the
      large ribosomal subunit. Interestingly, mutations in several other ribosomal
      protein-encoding genes also enhance the small-wing phenotype used in the original
      screen. Our work has therefore identified mutations in five previously
      uncharacterized Drosophila genes and provides in vivo evidence that normal organ
      growth requires optimal regulation of both pre-mRNA splicing and mRNA
      translation.

PMID- 15998721
TI  - Reevaluation of the role of the med-1 and med-2 genes in specifying the
      Caenorhabditis elegans endoderm.
AB  - The med-1 and med-2 genes encode a pair of essentially identical GATA factor
      related transcription factors that have been proposed to be necessary for
      specification of the C. elegans endoderm (intestine or E lineage) as well as part
      of the C. elegans mesoderm. med-1 and med-2 are proposed to be the direct
      downstream targets and the principal effectors of the maternally provided SKN-1
      transcription factor; med-1 and med-2 would thus occupy the pivotal interface
      between maternal and zygotic control of gene expression. The conclusion that med
      1 and med-2 are necessary for C. elegans endoderm specification was based on a
      partially penetrant (approximately 50%) loss of endoderm markers produced by RNA
      mediated interference (RNAi). To determine whether this partial penetrance
      reflects: (i) inefficient RNAi against early zygotic transcripts, (ii)
      experimental uncertainty in the expected level of endoderm loss in skn-1 nulls,
      or (iii) additional redundancy in the pathway of endoderm specification, we
      constructed worm strains that segregate embryos lacking both the med-1 gene
      (because of a gene-specific deletion) and the med-2 gene (using either of two
      chromosomal deficiencies). Contrary to expectations, we observe that only
      approximately 3-20% of med-2(-); med-1(-) embryos do not express markers of
      endoderm differentiation. Furthermore, we found no evidence for a maternal
      contribution of the med genes to endoderm specification. We conclude that the
      major pathway(s) for endoderm specification in C. elegans must be independent of
      the med-1 and med-2 genes.

PMID- 15998723
TI  - Recombination and the properties of Tajima's D in the context of approximate
      likelihood calculation.
AB  - I show that Tajima's D, a commonly used summary of the site-frequency spectrum
      for single-nucleotide polymorphism data, is a biased summary of the site
      frequency spectrum. Under neutral models, this bias depends on the population
      recombination rate. This bias of D in summarizing the data makes inference of
      demographic parameters sensitive to assumptions about recombination rates.

PMID- 15998722
TI  - Genetic interactions between mediator and the late G1-specific transcription
      factor Swi6 in Saccharomyces cerevisiae.
AB  - Swi6 associates with Swi4 to activate HO and many other late G(1)-specific
      transcripts in budding yeast. Genetic screens for suppressors of SWI6 mutants
      have been carried out. A total of 112 of these mutants have been identified and
      most fall into seven complementation groups. Six of these genes have been cloned
      and identified and they all encode subunits of the mediator complex. These
      mutants restore transcription to the HO-lacZ reporter in the absence of Swi6 and
      have variable effects on other Swi6 target genes. Deletions of other nonessential
      mediator components have been tested directly for suppression of, or genetic
      interaction with, swi6. Mutations in half of the known subunits of mediator show
      suppression and/or growth defects in combination with swi6. These phenotypes are
      highly variable and do not correlate with a specific module of the mediator.
      Mutations in tail module components sin4 and pgd1 showed both growth defects and
      suppression when combined with swi6, but a third tail component, gal11, showed
      neither. A truncated form of the essential Srb7 mediator subunit also suppresses
      swi6 mutations and shows a defect in recruitment of the tail module components
      Sin4, Pgd1, and Gal11 to the mediator complex.

PMID- 15998724
TI  - Gene expression during Drosophila wing morphogenesis and differentiation.
AB  - The simple cellular composition and array of distally pointing hairs has made the
      Drosophila wing a favored system for studying planar polarity and the
      coordination of cellular and tissue level morphogenesis. We carried out a gene
      expression screen to identify candidate genes that functioned in wing and wing
      hair morphogenesis. Pupal wing RNA was isolated from tissue prior to, during, and
      after hair growth and used to probe Affymetrix Drosophila gene chips. We
      identified 435 genes whose expression changed at least fivefold during this
      period and 1335 whose expression changed at least twofold. As a functional
      validation we chose 10 genes where genetic reagents existed but where there was
      little or no evidence for a wing phenotype. New phenotypes were found for 9 of
      these genes, providing functional validation for the collection of identified
      genes. Among the phenotypes seen were a delay in hair initiation, defects in hair
      maturation, defects in cuticle formation and pigmentation, and abnormal wing hair
      polarity. The collection of identified genes should be a valuable data set for
      future studies on hair and bristle morphogenesis, cuticle synthesis, and planar
      polarity.

PMID- 15998725
TI  - Genomic mutation in lines of Arabidopsis thaliana exposed to ultraviolet-B
      radiation.
AB  - Studies that have attempted to estimate the rate of deleterious mutation have
      typically been conducted under low levels of ultraviolet-B (UV-B) radiation, a
      naturally occurring mutagen. We conducted experiments to test whether the
      inclusion of natural levels of UV-B radiation in mutation-accumulation (MA)
      experiments influences the rate and effects of mildly deleterious mutation in the
      plant Arabidopsis thaliana. Ten generations of MA proved insufficient to observe
      significant changes in means or among-line variances in experimental lines
      maintained either with or without supplemental UV-B radiation. Maximum-likelihood
      estimates of mutation rate for total flower number revealed a small but
      significant rate of mutation for MA lines propagated under supplemental UV-B
      exposure, but not for those in which supplemental UV-B was omitted. A fraction of
      the flower number mutations under UV-B (approximately 25-30%) are estimated to
      increase flower number. Results from the application of transposon display to
      plant materials obtained after MA, in both the presence and absence of
      supplemental UV-B, suggest that the average rate of transposition for the class I
      and II transposable elements (TEs) surveyed was no more than 10(-4). Overall, the
      estimates of mutation parameters are qualitatively similar to what has been
      observed in other MA experiments with this species in which supplemental UV-B
      levels have not been used. As well, it appears that naturally occurring levels of
      UV-B do not lead to detectable increases in levels of transposable element
      activity.

PMID- 15998726
TI  - Extreme population structure and high interspecific divergence of the Silene Y
      chromosome.
AB  - Previous studies have demonstrated that the diversity of Y-linked genes is
      substantially lower than that of their X-linked homologs in the plant Silene
      latifolia. This difference has been attributed to selective sweeps, Muller's
      ratchet, and background selection, processes that are predicted to severely
      affect the evolution of the nonrecombining Y chromosome. We studied the DNA
      diversity of a noncoding region of the homologous genes DD44Y and DD44X, sampling
      S. latifolia populations from a wide geographical area and also including the
      closely related species S. dioica, S. diclinis, and S. heuffelii. On the Y
      chromosome of S. latifolia, we found substantial DNA diversity. Geographical
      population structure was far higher than on the X chromosome and differentiation
      between the species was also higher for the Y than for the X chromosome. Our
      findings indicate that the loss of genetic diversity on the Y chromosome in
      Silene occurs within local populations rather than within entire species. These
      results are compatible with background selection, Muller's ratchet, and local
      selective sweeps, but not with species-wide selective sweeps. The higher
      interspecific divergence of DD44Y, compared to DD44X, supports the hypothesis
      that Y chromosome differentiation between incipient species precedes reproductive
      isolation of the entire genome, forming an early stage in the process of
      speciation.

PMID- 15998727
TI  - Evolutionary conservation of Ceratitis capitata transformer gene function.
AB  - Transformer functions as a binary switch gene in the sex determination and sexual
      differentiation of Drosophila melanogaster and Ceratitis capitata, two insect
      species that separated nearly 100 million years ago. The TRA protein is required
      for female differentiation of XX individuals, while XY individuals express
      smaller, presumably nonfunctional TRA peptides and consequently develop into
      adult males. In both species, tra confers female sexual identity through a well
      conserved double-sex gene. However, unlike Drosophila tra, which is regulated by
      the upstream Sex-lethal gene, Ceratitis tra itself is likely to control a
      feedback loop that ensures the maintenance of the female sexual state. The
      putative CcTRA protein shares a very low degree of sequence identity with the TRA
      proteins from Drosophila species. However, in this study we show that a female
      specific Ceratitis Cctra cDNA encoding the putative full-length CcTRA protein is
      able to support the female somatic and germline sexual differentiation of D.
      melanogaster XX; tra mutant adults. Although highly divergent, CcTRA can
      functionally substitute for DmTRA and induce the female-specific expression of
      both Dmdsx and Dmfru genes. These data demonstrate the unusual plasticity of the
      TRA protein that retains a conserved function despite the high evolutionary rate.
      We suggest that transformer plays an important role in providing a molecular
      basis for the variety of sex-determining systems seen among insects.

PMID- 15998728
TI  - Two hybridization events define the population structure of Trypanosoma cruzi.
AB  - Genetic variation in Trypanosoma cruzi is likely a key determinant in
      transmission and pathogenesis of Chagas disease. We have examined nine loci as
      markers for the extant T. cruzi strains. Four distinct alleles were found for
      each locus, corresponding to the sequence classes present in the homozygous
      discrete typing units (DTUs) I, IIa, IIb, and IIc. The alleles in DTUs IIa and
      IIc showed a spectrum of polymorphism ranging from DTU I-like to DTU IIb-like, in
      addition to DTU-specific sequence variation. DTUs IId and IIe were
      indistinguishable, showing DTU homozygosity at one locus and heterozygosity with
      DTU IIb and IIc allelic sequences at eight loci. Recombination between the DTU
      IIb and IIc alleles is evidenced from mosaic polymorphisms. These data imply that
      two discrete hybridization events resulted in the formation of the current DTUs.
      We propose a model in which a fusion between ancestral DTU I and IIb strains gave
      rise to a heterozygous hybrid that homogenized its genome to become the
      homozygous progenitor of DTUs IIa and IIc. The second hybridization between DTU
      IIb and IIc strains that generated DTUs IId and IIe resulted in extensive
      heterozygosity with subsequent recombination of parental genotypes.

PMID- 15998729
TI  - Impairment of cytotype regulation of P-element activity in Drosophila
      melanogaster by mutations in the Su(var)205 gene.
AB  - Cytotype regulation of transposable P elements in the germ line of Drosophila
      melanogaster is associated with maternal transmission of P elements inserted at
      the left telomere of the X chromosome. This regulation is impaired in long-term
      stocks heterozygous for mutations in Suppressor of variegation 205 [Su(var)205],
      a gene implicated in the control of telomere length. Regulation by TP5, a
      structurally incomplete P element at the X telomere, is more profoundly impaired
      than regulation by TP6, a different incomplete P element inserted at the same
      site in a TAS repeat at the X telomere. Genetic analysis with the TP5 element
      indicates that its regulatory ability is not impaired in flies whose fathers came
      directly from a stock heterozygous for a Su(var)205 mutation, even when the flies
      themselves carry this mutation. However, it is impaired in flies whose
      grandfathers came from such a stock. Furthermore, this impairment occurs even
      when the Su(var)205 mutation is not present in the flies themselves or in their
      mothers. The impaired regulatory ability of TP5 persists for at least several
      generations after TP5 X chromosomes extracted from a long-term mutant Su(var)205
      stock are made homozygous in the absence of the Su(var)205 mutation. Impairment
      of TP5-mediated regulation is therefore not directly dependent on the Su(var)205
      mutation. However, it is characteristic of the six mutant Su(var)205 stocks that
      were tested and may be related to the elongated telomeres that develop in these
      stocks. Impairment of regulation by TP5 is also seen in a stock derived from
      Gaiano, a wild-type strain that has elongated telomeres due to a dominant
      mutation in the Telomere elongation (Tel) gene. Regulation by TP6 is not impaired
      in the Gaiano genetic background. The regulatory abilities of the TP5 and TP6
      elements are therefore not equally susceptible to the effects of elongated
      telomeres in the mutant Su(var)205 and Gaiano stocks.

PMID- 15998730
TI  - Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus.
AB  - Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus of the
      family Paramyxoviridae and are unique in that they exhibit a broad species
      tropism and cause fatal disease in both animals and humans. They infect cells
      through a pH-independent membrane fusion process mediated by their fusion and
      attachment glycoproteins. Previously, we demonstrated identical cell fusion
      tropisms for HeV and NiV and the protease-sensitive nature of their unknown cell
      receptor and identified a human cell line (HeLa-USU) that was nonpermissive for
      fusion and virus infection. Here, a microarray analysis was performed on the HeLa
      USU cells, permissive HeLa-CCL2 cells, and two other permissive human cell lines.
      From this analysis, we identified a list of genes encoding known and predicted
      plasma membrane surface-expressed proteins that were highly expressed in all
      permissive cells and absent from the HeLa-USU cells and rank-ordered them based
      on their relative levels. Available expression vectors containing the first 10
      genes were obtained and individually transfected into HeLa-USU cells. One clone,
      encoding human ephrin-B2 (EFNB2), was found capable of rendering HeLa-USU cells
      permissive for HeV- and NiV-mediated cell fusion as well as infection by live
      virus. A soluble recombinant EFNB2 could potently block fusion and infection and
      bind soluble recombinant HeV and NiV attachment glycoproteins with high affinity.
      Together, these data indicate that EFNB2 serves as a functional receptor for both
      HeV and NiV. The highly conserved nature of EFNB2 in humans and animals is
      consistent with the broad tropism exhibited by these emerging zoonotic viruses.

PMID- 15998731
TI  - Efficient hepatitis C virus cell culture system: what a difference the host cell
      makes.

PMID- 15998732
TI  - Synchronous neural activity in scale-free network models versus random network
      models.
AB  - Synchronous firing peaks at levels greatly exceeding background activity have
      recently been reported in neocortical tissue. A small subset of neurons is
      dominant in a large fraction of the peaks. To investigate whether this striking
      behavior can emerge from a simple model, we constructed and studied a model
      neural network that uses a modified Hopfield-type dynamical rule. We find that
      networks having a power-law ("scale-free") node degree distribution readily
      generate extremely large synchronous firing peaks dominated by a small subset of
      nodes, whereas random (Erdos-Renyi) networks do not. This finding suggests that
      network topology may play an important role in determining the nature and
      magnitude of synchronous neural activity.

PMID- 15998733
TI  - Computational prediction of native protein ligand-binding and enzyme active site
      sequences.
AB  - Recent studies reveal that the core sequences of many proteins were nearly
      optimized for stability by natural evolution. Surface residues, by contrast, are
      not so optimized, presumably because protein function is mediated through surface
      interactions with other molecules. Here, we sought to determine the extent to
      which the sequences of protein ligand-binding and enzyme active sites could be
      predicted by optimization of scoring functions based on protein ligand-binding
      affinity rather than structural stability. Optimization of binding affinity under
      constraints on the folding free energy correctly predicted 83% of amino acid
      residues (94% similar) in the binding sites of two model receptor-ligand
      complexes, streptavidin-biotin and glucose-binding protein. To explore the
      applicability of this methodology to enzymes, we applied an identical algorithm
      to the active sites of diverse enzymes from the peptidase, beta-gal, and
      nucleotide synthase families. Although simple optimization of binding affinity
      reproduced the sequences of some enzyme active sites with high precision,
      imposition of additional, geometric constraints on side-chain conformations based
      on the catalytic mechanism was required in other cases. With these modifications,
      our sequence optimization algorithm correctly predicted 78% of residues from all
      of the enzymes, with 83% similar to native (90% correct, with 95% similar,
      excluding residues with high variability in multiple sequence alignments).
      Furthermore, the conformations of the selected side chains were often correctly
      predicted within crystallographic error. These findings suggest that simple
      selection pressures may have played a predominant role in determining the
      sequences of ligand-binding and active sites in proteins.

PMID- 15998734
TI  - Annotation of cis-regulatory elements by identification, subclassification, and
      functional assessment of multispecies conserved sequences.
AB  - An important step toward improving the annotation of the human genome is to
      identify cis-acting regulatory elements from primary DNA sequence. One approach
      is to compare sequences from multiple, divergent species. This approach
      distinguishes multispecies conserved sequences (MCS) in noncoding regions from
      more rapidly evolving neutral DNA. Here, we have analyzed a region of
      approximately 238kb containing the human alpha globin cluster that was sequenced
      and/or annotated across the syntenic region in 22 species spanning 500 million
      years of evolution. Using a variety of bioinformatic approaches and correlating
      the results with many aspects of chromosome structure and function in this
      region, we were able to identify and evaluate the importance of 24 individual
      MCSs. This approach sensitively and accurately identified previously
      characterized regulatory elements but also discovered unidentified promoters,
      exons, splicing, and transcriptional regulatory elements. Together, these studies
      demonstrate an integrated approach by which to identify, subclassify, and predict
      the potential importance of MCSs.

PMID- 15998735
TI  - The phagosomal transporter A couples threonine acquisition to differentiation and
      replication of Legionella pneumophila in macrophages.
AB  - Differentiation in response to environmental cues is integral to the success of
      many intracellular pathogens. By characterizing a Legionella pneumophila mutant
      defective for differentiation in broth and replication in macrophages, we
      identified a subfamily of major facilitator superfamily transporters, here named
      Pht (phagosomal transporter), that also is conserved in two other vacuolar
      pathogens, Coxiella burnetii and Francisella tularensis. Biolog phenotype
      microarray analysis indicated that PhtA transports threonine, an essential amino
      acid. Either excess threonine or threonine peptides bypass phtA function. In
      minimal medium, phtA mutants do not replicate; in rich broth, the bacteria
      prematurely differentiate to the transmissive phase, as judged by the kinetics of
      flaA-gfp expression, heat resistance, and sodium sensitivity. PhtA is dispensable
      for transmissive L. pneumophila to establish and persist within a replication
      vacuole but is essential for their differentiation to the replicative phase,
      based on phenotypic and RT-PCR analysis. Accordingly, we propose that the Pht
      transporter family equips transmissive L. pneumophila, C. burnetii, and F.
      tularensis to assess their phagosomal nutrient supply before committing to
      reenter the cell cycle.

PMID- 15998736
TI  - The binding of the ubiquitous transcription factor Sp1 at the locus control
      region represses the expression of beta-like globin genes.
AB  - To investigate the function of transcription factor Sp1 in beta-like globin gene
      activation, we analyzed the recruitment of Sp1, fetal Kruppel-like factor 2
      (FKLF2), and related factors at the human beta-globin locus in a human fetal
      liver and mouse erythroleukemia hybrid cell (A181gamma cell) that contains a
      single copy of human chromosome 11. Sp1 binds at the GT boxes of the cis-elements
      throughout the beta-locus, but it is phosphorylated and lost over DNase I
      hypersensitive site (HS)2, HS3, HS4, and the human beta-globin gene promoter
      after A181gamma cell differentiation. The binding of FKLF2 at HS2 and HS3 was
      unchanged. Histone deacetylase 1, which could be recruited by Sp1, is also lost
      over HS2 and HS3 after differentiation, resulting in the acetylation of histones
      3 and 4 across the human beta-globin locus. We previously detected in vivo GT
      footprints over the beta-globin locus after A181gamma differentiation. Here, we
      report that after differentiation, the p300/CREB-binding protein-associated
      factor is recruited by FKLF2 to the locus control region to acetylate histones 3
      and 4 at the human beta-globin gene locus. Our results suggest that Sp1 is an
      inhibitor of beta-like globin gene transcription during erythroid terminal
      differentiation. Its phosphorylation and release allow the erythroid-specific
      FKLF2 or erythroid Kruppel-like factor to interact with other erythroid-specific
      transcription factors to initiate the transcription of beta-like globin genes.

PMID- 15998737
TI  - An integrated functional genomics and metabolomics approach for defining poor
      prognosis in human neuroendocrine cancers.
AB  - Human neuroendocrine (NE) cancers range from relatively indolent to highly
      aggressive. In this study, we combine functional genomics with metabolomics to
      identify features of NE cancers associated with a poor outcome. Analysis of
      GeneChip datasets of primary prostate tumors, as well as lymph node and liver
      metastases from transgenic mice with a NE cell cancer, plus derived NE cell lines
      yielded a signature of 446 genes whose expression is enriched in neoplastic mouse
      prostatic NE cells. This signature was used for in silico metabolic
      reconstructions of NE cell metabolism, directed liquid chromatography/tandem MS
      analysis of metabolites in prostatic NE tumors and cell lines, and analysis of
      GeneChip datasets of human NE tumors with good or poor prognoses. The results
      indicate that a distinguishing feature of poor-prognosis NE tumors is a glutamic
      acid decarboxylase-independent pathway for production of GABA and a pathway for
      production of imidazole-4-acetate that involves dopa decarboxylase and a membrane
      associated amine oxidase, amiloride-binding protein 1. Electrophysiological
      studies disclosed that imidazole-4-acetate can bind and activate GABA(A)
      receptors expressed by transformed NE cells, thus providing a previously
      uncharacterized paradigm for NE tumor cell signaling. Transcriptional, metabolic,
      and electrophysiologic features of transformed mouse NE cells are also evident in
      neural progenitor cells.

PMID- 15998738
TI  - Operational effectiveness of suicide-bomber-detector schemes: a best-case
      analysis.
AB  - Standoff explosives-detection technologies allow, in principle, for the detection
      of pedestrian suicide bombers, although such sensors are not yet sufficiently
      affordable and reliable to justify widespread deployment. What if they were?
      Assuming the availability of cheap, perfectly sensitive and specific suicide
      bomber-sensing devices, we analyze the operational effectiveness of sensor-based
      detector schemes in reducing casualties from random suicide-bombing attacks. We
      model the number of casualties resulting from pedestrian suicide bombings absent
      intervention, the reduction in casualties from alternative interventions, given
      timely detection of a suicide-bombing attack, and the probability of timely
      detection under best-case assumptions governing the performance of suicide-bomber
      detector schemes in two different urban settings. Even under such optimistic
      assumptions, we find that the widespread deployment of suicide-bomber detectors
      will not reliably result in meaningful casualty reductions. Relaxing the best
      case assumptions only makes matters worse. Investment in intelligence-gathering
      to prevent suicide bombers before they attack seems a wiser strategy than relying
      on sensor-based suicide-bomber-detector schemes.

PMID- 15998739
TI  - Stochastic model for Soj relocation dynamics in Bacillus subtilis.
AB  - The Bacillus subtilis Spo0J/Soj proteins, implicated in chromosome segregation
      and transcriptional regulation, show striking dynamics: Soj undergoes irregular
      relocations from pole to pole or nucleoid to nucleoid. Here, we report on a
      mathematical model of the Soj dynamics. Our model, which is closely based on the
      available experimental data, readily generates dynamic Soj relocations. We show
      that the irregularity of the relocations may be due to the stochastic nature of
      the underlying Spo0J/Soj interactions and diffusion. We propose explanations for
      the behavior of several Spo0J/Soj mutants, including the "freezing" of the Soj
      dynamics observed in filamentous cells. Our approach underlines the importance of
      incorporating stochastic effects when modeling spatiotemporal protein dynamics
      inside cells.

PMID- 15998740
TI  - Stable barley chromosomes without centromeric repeats.
AB  - The satellite sequences (AGGGAG)(n) and Ty3/gypsy-like retrotransposons are known
      to localize at the barley centromeres. Using a gametocidal system, which induces
      chromosomal mutations in barley chromosomes added to common wheat, we obtained an
      isochromosome for the short arm of barley chromosome 7H (7HS) that lacked the
      barley-specific satellite sequence (AGGGAG)(n). Two telocentric derivatives of
      the isochromosome arose in the progeny: 7HS* with and 7HS** without the
      pericentromeric C-band. FISH analysis demonstrated that both telosomes lacked not
      only the barley-specific centromeric (AGGGAG)(n) repeats and retroelements but
      also any of the known wheat centromeric tandem repeats, including the 192-bp, 250
      bp, and TaiI sequences. Although they lacked these centromeric repeats, 7HS* and
      7HS** both showed normal mitotic and meiotic transmission. Translocation of
      barley centromeric repeats to a wheat chromosome 4A did not generate a dicentric
      chromosome. Indirect immunostaining revealed that all tested centromere-specific
      proteins (rice CENH3, maize CENP-C, and putative barley homologues of the yeast
      kinetochore proteins CBF5 and SKP1) and histone H3 phosphorylated at serines 10
      and 28 localized at the centromeric region of 7HS*. We conclude that the barley
      centromeric repeats are neither sufficient nor obligatory to assemble
      kinetochores, and we discuss the possible formation of a novel centromere in a
      barley chromosome.

PMID- 15998741
TI  - Estimating the total genetic diversity of a spatial field population from a
      sample and implications of its dependence on habitat area.
AB  - The total genetic diversity of a species is a key factor in its persistence and
      conservation. Because realistic sample sizes are far smaller than the total
      population, it is impractical to exhaustively characterize diversity of most
      populations. Here, we demonstrate the possibility of calculating the genetic
      diversity of a spatial population from a sample using genealogical models. We
      trace the history of a population by simulating the locations of the ancestors of
      a particular sample of the population backwards in time. We use this method to
      estimate the genetic diversity of the global population of Pseudomonas bacteria.
      The same results are obtained whether using a global sample or a subsample
      restricted to a particular geographic region (California). The results are also
      validated by comparing additional predictions of the model to the data.
      Furthermore, we use these results to show that the level of genetic diversity in
      a population depends strongly on the size of its habitat, much more strongly than
      does biodiversity as measured by the number of species. The strong dependence of
      diversity on habitat area has significant implications for conservation
      strategies.

PMID- 15998742
TI  - Agrobacterium tumefaciens increases cytokinin production in plastids by modifying
      the biosynthetic pathway in the host plant.
AB  - Agrobacterium tumefaciens infects plants and induces the formation of tumors
      called "crown galls" by integrating the transferred-DNA (T-DNA) region of the Ti
      plasmid into the plant nuclear genome. Tumors are formed because the T-DNA
      encodes enzymes that modify the synthesis of two plant growth hormones, auxin and
      cytokinin (CK). Here, we show that a CK biosynthesis enzyme, Tmr, which is
      encoded by the Agrobacterium T-DNA region, is targeted to and functions in
      plastids of infected plant cells, despite having no typical plastid-targeting
      sequence. Evidence is provided that Tmr is an adenosine phosphate
      isopentenyltransferase (IPT) that creates a new CK biosynthesis bypass by using 1
      hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBDP) as a substrate. Unlike in
      the conventional CK biosynthesis pathway in plants, trans-zeatin-type CKs are
      produced directly without the requirement for P450 monooxygenase-mediated
      hydroxylation. Consistent with the plastid localization of Tmr, HMBDP is an
      intermediate in the methylerythritol phosphate pathway, a plastid-localized
      biosynthesis route for universal isoprenoid precursors. These results demonstrate
      that A. tumefaciens modifies CK biosynthesis by sending a key enzyme into
      plastids of the host plant to promote tumorigenesis.

PMID- 15998743
TI  - Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase
      mediates microglial toxicity to oligodendrocytes.
AB  - Reactive microglia in the CNS have been implicated in the pathogenesis of white
      matter disorders, such as periventricular leukomalacia and multiple sclerosis.
      However, the mechanism by which activated microglia kill oligodendrocytes (OLs)
      remains elusive. Here we show that lipopolysaccharide (LPS)-induced death of
      developing OLs is caused by microglia-derived peroxynitrite, the reaction product
      of nitric oxide (NO) and superoxide anion. Blocking peroxynitrite formation with
      nitric oxide synthase inhibitors, superoxide dismutase mimics, or a decomposition
      catalyst abrogated the cytotoxicity. Only microglia, but not OLs, expressed
      inducible NO synthase (iNOS) after LPS challenge; microglia from iNOS knockout
      mice were not cytotoxic upon activation. The molecular source for superoxide was
      identified as the superoxide-generating enzyme NADPH oxidase. The oxidase was
      activated upon LPS exposure, and its inhibition prevented microglial toxicity
      toward OLs. Furthermore, microglia isolated from mice deficient in the catalytic
      component of the oxidase, gp91(phox), failed to induce cell death. Our results
      reveal a role for NADPH oxidase in LPS-induced OL death and suggest that
      peroxynitrite produced by iNOS and NADPH oxidase in activated microglia may play
      an important role in the pathogenesis of white matter disorders.

PMID- 15998744
TI  - Temporal and spatial transcriptional programs in murine kidney development.
AB  - We have performed a systematic temporal and spatial expression profiling of the
      developing mouse kidney using Compugen long-oligonucleotide microarrays. The
      activity of 18,000 genes was monitored at 24-h intervals from 10.5-day-postcoitum
      (dpc) metanephric mesenchyme (MM) through to neonatal kidney, and a cohort of
      3,600 dynamically expressed genes was identified. Early metanephric development
      was further surveyed by directly comparing RNA from 10.5 vs. 11.5 vs. 13.5dpc
      kidneys. These data showed high concordance with the previously published dynamic
      profile of rat kidney development (Stuart RO, Bush KT, and Nigam SK. Proc Natl
      Acad Sci USA 98: 5649-5654, 2001) and our own temporal data. Cluster analyses
      were used to identify gene ontological terms, functional annotations, and
      pathways associated with temporal expression profiles. Genetic network analysis
      was also used to identify biological networks that have maximal transcriptional
      activity during early metanephric development, highlighting the involvement of
      proliferation and differentiation. Differential gene expression was validated
      using whole mount and section in situ hybridization of staged embryonic kidneys.
      Two spatial profiling experiments were also undertaken. MM (10.5dpc) was compared
      with adjacent intermediate mesenchyme to further define metanephric commitment.
      To define the genes involved in branching and in the induction of nephrogenesis,
      expression profiling was performed on ureteric bud (GFP+) FACS sorted from HoxB7
      GFP transgenic mice at 15.5dpc vs. the GFP- mesenchymal derivatives. Comparisons
      between temporal and spatial data enhanced the ability to predict function for
      genes and networks. This study provides the most comprehensive temporal and
      spatial survey of kidney development to date, and the compilation of these
      transcriptional surveys provides important insights into metanephric development
      that can now be functionally tested.

PMID- 15998745
TI  - Enhanced resistance to fatigue and altered calcium handling properties of
      sarcalumenin knockout mice.
AB  - Sarcalumenin is a Ca2+-binding protein located in the sarcoplasmic reticulum of
      striated muscle cells, the physiological function of which has not been fully
      determined yet. Using sarcalumenin knockout (sar(-/-)) mice, we showed that sar
      ablation altered store-operated Ca2+ entry (SOCE) and enhanced muscle fatigue
      resistance. Sar(-/-) mice fatigued less with treadmill exercise, and intact
      isolated soleus and extensor digitorum longus muscles from sar(-/-) mice were
      more resistant to intermittent fatiguing stimulation than those from wild-type
      mice. Enhanced SOCE was observed in the sar(-/-) muscles. Biochemical analysis
      revealed that sar(-/-) muscles contained significantly elevated expression of
      mitsugumin 29 (MG29), a synaptophysin-related membrane protein located in the
      triad junction of skeletal muscle. Because the ablation of mg29 has been shown to
      cause increased fatigability and dysfunction of SOCE, the enhanced SOCE activity
      seen in sar(-/-) muscle may be correlated with the increased expression of MG29.
      Our data suggest that systemic ablation of sarcalumenin caused enhanced
      resistance to muscle fatigue by compensatory changes in Ca2+ regulatory proteins
      that effect SOCE.

PMID- 15998746
TI  - Summaries for patients. Soybean protein may lower blood pressure.

PMID- 15998747
TI  - Summaries for patients. Acupuncture to treat fibromyalgia pain.

PMID- 15998748
TI  - Summaries for patients. Screening for HIV: U.S. Preventive Services Task Force
      recommendations.

PMID- 15998749
TI  - Effect of soybean protein on blood pressure: a randomized, controlled trial.
AB  - BACKGROUND: Epidemiologic studies suggest that vegetable protein intake is
      inversely related to blood pressure. OBJECTIVE: To examine the effect of soybean
      protein supplementation on blood pressure in persons with prehypertension or
      stage 1 hypertension. DESIGN: Randomized, double-blind, controlled trial.
      SETTING: Three communities in the People's Republic of China. PATIENTS: 302
      participants 35 to 64 years of age with an initial untreated systolic blood
      pressure of 130 to 159 mm Hg, diastolic blood pressure of 80 to 99 mm Hg, or
      both. INTERVENTION: Study participants were randomly assigned to receive 40 g of
      isolated soybean protein supplements per day or complex carbohydrate control for
      12 weeks; 91.4% completed the intervention. MEASUREMENTS: Blood pressure
      measurements were obtained by using random-zero sphygmomanometers at baseline and
      at 6 and 12 weeks. RESULTS: At baseline, the mean systolic and diastolic blood
      pressures were 135.0 mm Hg (SD 10.9) and 84.7 mm Hg (SD 6.9), respectively.
      Compared with the control group, the net changes in systolic blood pressure and
      diastolic blood pressure were -4.31 mm Hg (95% CI, -2.11 to -6.51 mm Hg; P <
      0.001) and -2.76 mm Hg (CI, -1.35 to -4.16 mm Hg; P < 0.001), respectively, after
      the 12-week intervention. The net changes in systolic and diastolic blood
      pressure reductions were -7.88 mm Hg (CI, -4.66 to -11.1 mm Hg) and -5.27 mm Hg
      (CI, -3.05 to -7.49 mm Hg), respectively, in persons with hypertension and -2.34
      mm Hg (CI, 0.48 to -5.17 mm Hg) and -1.28 mm Hg (CI, 0.52 to -3.07 mm Hg),
      respectively, in those without hypertension. LIMITATIONS: This trial did not
      examine whether the blood pressure reduction was due to protein or isoflavones in
      soybean. CONCLUSIONS: Soybean protein supplementation resulted in a reduction in
      systolic and diastolic blood pressure. These findings suggest that increased
      intake of soybean protein may play an important role in preventing and treating
      hypertension.

PMID- 15998750
TI  - A randomized clinical trial of acupuncture compared with sham acupuncture in
      fibromyalgia.
AB  - BACKGROUND: Fibromyalgia is a common chronic pain condition for which patients
      frequently use acupuncture. OBJECTIVE: To determine whether acupuncture relieves
      pain in fibromyalgia. DESIGN: Randomized, sham-controlled trial in which
      participants, data collection staff, and data analysts were blinded to treatment
      group. SETTING: Private acupuncture offices in the greater Seattle, Washington,
      metropolitan area. PATIENTS: 100 adults with fibromyalgia. INTERVENTION: Twice
      weekly treatment for 12 weeks with an acupuncture program that was specifically
      designed to treat fibromyalgia, or 1 of 3 sham acupuncture treatments:
      acupuncture for an unrelated condition, needle insertion at nonacupoint
      locations, or noninsertive simulated acupuncture. MEASUREMENTS: The primary
      outcome was subjective pain as measured by a 10-cm visual analogue scale ranging
      from 0 (no pain) to 10 (worst pain ever). Measurements were obtained at baseline;
      1, 4, 8, and 12 weeks of treatment; and 3 and 6 months after completion of
      treatment. Participant blinding and adverse effects were ascertained by self
      report. The primary outcomes were evaluated by pooling the 3 sham-control groups
      and comparing them with the group that received acupuncture to treat
      fibromyalgia. RESULTS: The mean subjective pain rating among patients who
      received acupuncture for fibromyalgia did not differ from that in the pooled sham
      acupuncture group (mean between-group difference, 0.5 cm [95% CI, -0.3 cm to 1.2
      cm]). Participant blinding was adequate throughout the trial, and no serious
      adverse effects were noted. LIMITATIONS: A prescription of acupuncture at fixed
      points may differ from acupuncture administered in clinical settings, in which
      therapy is individualized and often combined with herbal supplementation and
      other adjunctive measures. A usual-care comparison group was not studied.
      CONCLUSION: Acupuncture was no better than sham acupuncture at relieving pain in
      fibromyalgia.

PMID- 15998751
TI  - Reporting of harm in randomized, controlled trials of nonpharmacologic treatment
      for rheumatic disease.
AB  - BACKGROUND: Reports of clinical trials usually emphasize benefits and give less
      attention to harms. PURPOSE: To compare the reporting of harm in trials of
      pharmacologic and nonpharmacologic treatment. DATA SOURCES: MEDLINE and the
      Cochrane Central Register of Controlled Trials. STUDY SELECTION: Reports of
      randomized, controlled trials assessing treatment of rheumatic disease that were
      published between January 1999 and January 2005. DATA EXTRACTION: A standardized
      abstraction form was used to extract data. DATA SYNTHESIS: 193 articles were
      analyzed. After adjustment for medical area, sample size, funding source, and
      multicenter trials, data on harm were more often described in pharmacologic
      treatment reports than in nonpharmacologic treatment reports in reporting adverse
      events (odds ratio, 5.2 [95% CI, 2.1 to 12.9]), reporting withdrawals due to
      adverse events (odds ratio, 4.6 [CI, 2.0 to 10.9]), reporting severity (odds
      ratio, 3.7 [CI, 1.5 to 9.1]), and allocating space for describing harm (odds
      ratio, 1.6 [CI, 1.2 to 2.3]). LIMITATIONS: Extrapolating results to trials in
      areas other than rheumatic disease is questionable. CONCLUSIONS: The lack of
      reporting harm in trials assessing nonpharmacologic treatment in rheumatic
      disease is an important barrier to evaluating the benefit-harm balance of
      nonpharmacologic treatments.

PMID- 15998752
TI  - High and rising health care costs. Part 4: can costs be controlled while
      preserving quality?
AB  - Several interrelated strategies involving physician leadership and participation
      have been proposed to contain health care costs while preserving or improving
      quality. These include programs targeting the 10% of the population that incurs
      70% of health care expenditures, disease management programs to prevent costly
      complications of chronic conditions, efforts to reduce medical errors, the
      strengthening of primary care practice, decision support tools to avoid
      inappropriate services, and improved diffusion of technology assessment. An
      example of a cost-reducing, quality-enhancing program is post-hospital nurse
      monitoring and intervention for patients at high risk for repeated
      hospitalization for congestive heart failure. Disease management programs that
      target groups with a chronic condition rather than focusing efforts on high
      utilizing individuals may be effective in improving quality but may not reduce
      costs. Error reduction has great potential to improve quality while reducing
      costs, although the probable cost reduction is a small portion of national health
      care expenditures. Access to primary care has been shown to correlate with
      reduced hospital use while preserving quality. Inappropriate care and overuse of
      new technologies can be reduced through shared decision-making between well
      informed physicians and patients. Physicians have a central role to play in
      fostering these quality-enhancing strategies that can help to slow the growth of
      health care expenditures.

PMID- 15998753
TI  - Screening for HIV: recommendation statement.

PMID- 15998754
TI  - Prenatal screening for HIV: A review of the evidence for the U.S. Preventive
      Services Task Force.
AB  - BACKGROUND: Each year in the United States, 6000 to 7000 women with HIV give
      birth. The management and outcomes of prenatal HIV infection have changed
      substantially since the U.S. Preventive Services Task Force issued
      recommendations in 1996. PURPOSE: To synthesize current evidence on risks and
      benefits of prenatal screening for HIV infection. DATA SOURCES: MEDLINE, the
      Cochrane Library, reference lists, and experts. STUDY SELECTION: Studies of
      screening, risk factor assessment, accuracy of testing, follow-up testing, and
      efficacy of interventions. DATA EXTRACTION: Data on settings, patients,
      interventions, and outcomes were abstracted for included studies; quality was
      graded according to criteria developed by the Task Force. DATA SYNTHESIS: No
      published studies directly link prenatal screening for HIV with clinical
      outcomes. In developed countries, the rate of mother-to-child transmission from
      untreated HIV-infected women is 14% to 25%. Targeted screening based on risk
      factors would miss a substantial proportion of infected women. "Opt-out" testing
      policies appear to increase uptake rates. Standard HIV testing is highly (>99%)
      sensitive and specific, and initial studies of rapid HIV tests found that both
      types of testing had similar accuracy. Rapid testing can facilitate timely
      interventions in persons testing positive. Recommended interventions (combination
      antiretroviral regimens, elective cesarean section in selected patients, and
      avoidance of breastfeeding) are associated with transmission rates of 1% to 2%
      and appear acceptable to pregnant women. LIMITATIONS: Long-term safety data for
      antiretroviral agents are not yet available. Data are insufficient to accurately
      estimate the benefits of screening on long-term maternal disease progression or
      other clinical outcomes, such as horizontal transmission. CONCLUSIONS:
      Identification and treatment of asymptomatic HIV infection in pregnant women can
      greatly decrease mother-to-child transmission rates.

PMID- 15998755
TI  - Screening for HIV: a review of the evidence for the U.S. Preventive Services Task
      Force.
AB  - BACKGROUND: HIV infection affects 850,000 to 950,000 persons in the United
      States. The management and outcomes of HIV infection have changed substantially
      since the U.S. Preventive Services Task Force issued recommendations in 1996.
      PURPOSE: To synthesize the evidence on risks and benefits of screening for HIV
      infection. DATA SOURCES: MEDLINE, the Cochrane Library, reference lists, and
      experts. STUDY SELECTION: Studies of screening, risk factor assessment, accuracy
      of testing, follow-up testing, and efficacy of interventions. DATA EXTRACTION:
      Data on settings, patients, interventions, and outcomes were abstracted for
      included studies; quality was graded according to criteria developed by the Task
      Force. DATA SYNTHESIS: No trials directly link screening for HIV with clinical
      outcomes. Many HIV-infected persons in the United States currently receive
      diagnosis at advanced stages of disease, and almost all will progress to AIDS if
      untreated. Screening based on risk factors could identify persons at
      substantially higher risk but would miss a substantial proportion of those
      infected. Screening tests for HIV are extremely (>99%) accurate. Acceptance rates
      for screening and use of recommended interventions vary widely. Highly active
      antiretroviral therapy (HAART) substantially reduces the risk for clinical
      progression or death in patients with immunologically advanced disease. Along
      with other adverse events, HAART is associated with an increased risk for
      cardiovascular complications, although absolute rates are low after 3 to 4 years.
      LIMITATIONS: Data are insufficient to estimate the effects of screening and
      interventions on transmission rates or in patients with less immunologically
      advanced disease. Long-term data on adverse events associated with HAART are not
      yet available. CONCLUSIONS: Benefits of HIV screening appear to outweigh harms.
      The yield from screening higher-prevalence populations would be substantially
      higher than that from screening the general population.

PMID- 15998756
TI  - Nutrition and blood pressure: is protein one link? Toward a strategy of
      hypertension prevention.

PMID- 15998757
TI  - Health care expenditures reexamined.

PMID- 15998758
TI  - An editorial update: what level of blood pressure control in chronic kidney
      disease?

PMID- 15998759
TI  - Unintended consequences: the accreditation council for graduate medical education
      work-hour rules in practice.

PMID- 15998760
TI  - Clinical experience and quality of health care.

PMID- 15998761
TI  - Clinical experience and quality of health care.

PMID- 15998762
TI  - Clinical experience and quality of health care.

PMID- 15998763
TI  - Clinical experience and quality of health care.

PMID- 15998764
TI  - Clinical experience and quality of health care.

PMID- 15998765
TI  - "Practice makes perfect"...or does it?

PMID- 15998766
TI  - "Practice makes perfect"...or does it?

PMID- 15998768
TI  - Calcium absorptive efficiency is positively related to body size.
AB  - BACKGROUND: Calcium absorption efficiency is a more important determinant of
      calcium balance than calcium intake itself. The sources of variability in
      absorptive performance are only partly elucidated. PURPOSE: The aim of the study
      was to explore the relationship between body size and calcium absorption
      efficiency. DESIGN AND SETTING: Metabolic studies were performed on an inpatient
      metabolic unit in an academic health sciences center. SUBJECTS: One hundred
      seventy-eight women, with an average age of 50.2 yr, were studied from one to
      five times and yielded an aggregate data set containing 633 individual studies.
      METHODS: Calcium absorption fraction was measured by the dual-tracer method.
      Observed values were expressed as residuals from predicted values for each
      woman's actual calcium intake, using the previously published relationship
      between intake and absorption. RESULTS: Absorption residuals were significantly
      positively correlated with height, weight, and surface area, and after adjusting
      for estrogen status, these body size variables accounted for approximately 4% of
      the total variability. CONCLUSION: The magnitude of the effect is such that a
      woman 1.8 m in height would absorb 30+% more calcium from a given intake than a
      woman 1.4 m tall.

PMID- 15998767
TI  - KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases
      myocyte-enriched calcineurin interacting protein 1 expression and chronically
      inhibits calcineurin activity.
AB  - OBJECTIVE: Tumor metastasis is a critical determinant of death from cancer.
      Metastin, a product of the KiSS-1 gene, is an endogenously expressed metastasis
      suppressor that is the ligand for G protein-coupled receptor 54 (GPR54), a Gq/11
      coupled receptor. In the present study, our goal was to define the basis of GPR54
      action using thyroid cancer cells as a model. DESIGN AND RESULTS: We used GPR54
      null thyroid cancer cells to create a stable GPR54 overexpression model. Cell
      growth and cell migration of the GPR54-expressing lines were inhibited by
      recombinant metastin, and metastin stimulated the protein kinase C, ERK, and
      phosphatidylinositol-3-kinase pathways. To identify metastin-regulated genes, we
      performed microarray analyses using RNA isolated from GPR54 stable transfectants
      before and after 1 and 24 h of metastin stimulation. Consistent increases in
      expression of the gene encoding myocyte-enriched calcineurin interacting protein
      1 (MCIP-1), an inhibitor of calcineurin, were identified and confirmed using real
      time RT-PCR and Western blot. Functionally, metastin treatment of GPR54
      expressing cells initially increased calcineurin activity, followed by a
      prolonged reduction in calcineurin activity for 24 and 48 h, consistent with the
      pattern of MCIP-1 expression. In addition, treatment with cyclosporin A, a
      calcineurin inhibitor, blocked cell migration. Lymph node metastasis in papillary
      thyroid cancers demonstrated loss of MCIP-1 expression in comparison with primary
      tumors. CONCLUSIONS: These data suggest a role for MCIP-1 and calcineurin
      inhibition in GPR54-mediated metastasis suppression in human cancers.

PMID- 15998769
TI  - Effects of a beta-blocker on bone turnover in normal postmenopausal women: a
      randomized controlled trial.
AB  - INTRODUCTION: The central nervous system has been demonstrated to regulate bone
      mass in mice, possibly via the beta2-adrenoreceptors on osteoblasts. beta
      blockers increase bone mass in mice, and some observational studies have
      suggested a beneficial effect of these drugs on bone in humans EXPERIMENTAL
      SUBJECTS: We studied 41 normal postmenopausal women. MATERIALS AND METHODS: We
      conducted a randomized, placebo- controlled trial, comparing the effects on bone
      markers of propranolol 160 mg/d and placebo over 3 months. RESULTS: Serum
      osteocalcin declined by almost 20% in the first 2 wk of propranolol treatment,
      and this effect increased over time (P < 0.0001). Other osteoblast markers,
      procollagen type-I N-terminal propeptide and total alkaline phosphatase activity,
      were not significantly changed by propranolol. Urine free deoxypyridinoline
      declined by approximately 10% between 0 and 6 wk (P = 0.019) in the beta-blocker
      group and was stable thereafter. Serum C-terminal telopeptide of type I collagen
      also showed a small decrease, but this was not significantly different between
      groups. Serum albumin concentrations decreased by more than 2 g/liter in the
      first 2 wk of propranolol treatment, remaining stable subsequently (P = 0.007).
      Serum creatinine tended to increase in the propranolol group (P = 0.06), as did
      weight. Bone densities in the lumbar spine and total proximal femur did not
      change significantly in either group. CONCLUSIONS: The present study provides no
      evidence that beta-blocker drugs stimulate bone formation; if anything,
      propranolol reduces osteoblast activity. It also influences renal function and
      fluid balance, effects that might indirectly affect bone metabolism. Current
      evidence does not justify the use of beta-blockers for treatment of osteoporosis.

PMID- 15998770
TI  - Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy
      adolescents.
AB  - CONTEXT: Anorexia nervosa (AN) in adolescents is associated with low bone mineral
      density (BMD) and increases in ghrelin secretion, an orexigenic GH secretagogue
      that stimulates osteoblast proliferation in vitro. OBJECTIVE: We hypothesized
      that ghrelin may have independent effects on bone in AN adolescents. STUDY
      DESIGN, SUBJECTS, AND OUTCOME MEASURES: Frequent sampling was performed overnight
      every 30 min for 12 h in 23 adolescent AN girls aged 12-18 yr and 21 controls of
      comparable maturity. Ghrelin, leptin, cortisol, and GH secretion were examined
      using Cluster and deconvolution. We measured BMD and body composition (dual
      energy x-ray absorptiometry) and carboxy-terminal peptide of type I procollagen
      and N-telopeptide levels. RESULTS: In healthy adolescents, ghrelin secretion
      strongly predicted BMD; secretory burst mass being the strongest predictor of
      lumbar spine (LS) bone mineral apparent density (BMAD) (r = 0.66, P = 0.003), LS
      BMAD z-scores (BMAD-z) (r = 0.59, P = 0.01), hip BMD (r = 0.55, P = 0.02), and
      hip BMD-z (r = 0.52, P = 0.03). When body composition measures (body mass index,
      lean and fat mass), and hormonal predictors (GH, IGF-I, cortisol, leptin, and
      estradiol) were entered into a regression model with ghrelin secretion to
      determine independent BMD predictors, ghrelin was the strongest predictor of LS
      BMAD, BMAD-z, hip BMD, and hip BMD-z, contributing to 43, 30, 26, and 19% of the
      variability, respectively, independent of GH or cortisol effects. Conversely, in
      AN, ghrelin secretion did not predict LS BMAD or hip-z and weakly predicted LS
      BMAD-z and hip BMD. Ghrelin did not predict carboxy-terminal peptide of type I
      procollagen or N-telopeptide/creatinine, which were predicted by GH and cortisol.
      CONCLUSION: Ghrelin secretion predicts bone density independent of body
      composition, the GH-IGF-I axis, cortisol, or estradiol in healthy girls but not
      in those with AN.

PMID- 15998771
TI  - Adult height and pubertal growth in Turner syndrome after treatment with
      recombinant growth hormone.
AB  - OBJECTIVE: The objective of this study was to evaluate factors affecting adult
      height (AH) in patients with Turner syndrome treated with GH. DESIGN: The study
      design was a population-based cohort study. SETTING: The setting was The StaTur
      Study, a register of patients treated in France between 1986 and 1997, followed
      for a mean of 9.3 yr. PATIENTS: We followed 704 of the 891 eligible patients
      (79%) to AH. INTERVENTION: GH (0.8 +/- 0.2 IU/kg.wk; 0.26 +/- 0.06 mg/kg.wk; mean
      +/- sd) was administered for 5.0 +/- 2.2 yr. Puberty was classified as
      spontaneous (10%), spontaneous with secondary estrogens (13%), or induced (77%).
      Estrogen treatment was initiated at 15.0 +/- 1.9 yr of age in those with induced
      puberty. MAIN OUTCOME MEASURE: The main outcome measure was multivariate analysis
      of AH after grouping potential predictors. RESULTS: The mean AH was 149.9 +/- 6.1
      cm, 8.5 cm above projected height. The model explained 90% of the variance, with
      major effects of age at initiation and duration of treatment. Other factors
      included birth length, target height, bone age delay and weight at initiation of
      treatment, age at pubertal onset, GH dose, and number of injections per week. Age
      at introduction of estrogens was not a predictor, and the use of percutaneous vs.
      oral estrogens was associated with greater height (+2.1 cm; 95% confidence
      interval, 1.00-3.25). CONCLUSIONS: Our results support the early initiation of GH
      treatment and induction of puberty at a physiological age to achieve optimal AH.
      They suggest that GH should be injected daily, and percutaneous estrogens used.
      These results should be considered in the context of the lack of demonstrable
      influence of AH on psycho-social outcomes, uncertainties regarding long-term
      safety, and treatment cost.

PMID- 15998772
TI  - Relationship of volumetric bone density and structural parameters at different
      skeletal sites to sex steroid levels in women.
AB  - CONTEXT: Although estrogen clearly plays a central role in regulating bone mass
      in women, studies in men have suggested that there may be a threshold
      bioavailable (bio) estradiol (E2) level below which aging men begin to lose bone
      and that the threshold for estrogen deficiency in cortical bone may be
      considerably lower than that in trabecular bone. There are no data testing this
      in women. OBJECTIVE: Our objective was to assess volumetric bone mineral density
      (vBMD) and bone geometry by quantitative computed tomography and relate these to
      circulating bio E2 and bio testosterone levels. DESIGN: We studied a cross
      sectional, age-stratified population sample of 235 women (age, 21-97 yr).
      RESULTS: vBMD/structural parameters were not related to sex steroid levels in
      young premenopausal women (age, 20-39 yr) with a median bio E2 level of 17 pg/ml
      (63 pmol/liter). By contrast, bio E2 and bio testosterone levels were both
      significantly associated with trabecular and cortical vBMD and cortical area at
      multiple sites in late postmenopausal women (age > or = 60 yr) who had a median
      bio E2 level of 3 pg/ml (11 pmol/liter). Late premenopausal and early
      postmenopausal women (age, 40-59 yr) with an intermediate median bio E2 level of
      11 pg/ml (42 pmol/liter) showed age-adjusted correlations of bio E2 levels with
      trabecular but not with cortical vBMD. CONCLUSIONS: In women, bio E2 levels are
      associated with vBMD and some structural bone parameters at low but not high bio
      E2 levels. Similar to findings in men, the threshold for estrogen deficiency in
      cortical bone in women appears to be lower than that in trabecular bone.

PMID- 15998773
TI  - Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances
      thyroid carcinoma cell invasiveness.
AB  - The transmembrane glycoprotein CD44v6 is overexpressed in most papillary thyroid
      carcinomas (PTC). We previously reported that osteopontin (OPN), a secreted
      glycoprotein that functions as a ligand for CD44v6, is overexpressed in
      thyrocytes transformed by the RET/PTC oncogene. OBJECTIVE: In this study we asked
      whether OPN is overexpressed in human PTC samples, and whether its expression
      correlates with clinical and histological features of the tumors. Furthermore, we
      wanted to establish the functional role of the CD44-OPN axis in thyroid
      tumorigenesis. DESIGN: Thyroid samples from 117 patients who had undergone
      surgical resection of the thyroid gland for benign or malignant lesions were
      collected. OPN and CD44 expressions were evaluated by immunohistochemistry with
      specific monoclonal antibodies. OPN expression was correlated with different PTC
      histological variants, lymph node metastasis, and PTC size. RESULTS: In this
      study we show that OPN is overexpressed in human PTCs with respect to normal
      thyroid tissue, follicular adenomas, and multinodular goiters (P < 0.05). The
      prevalence and intensity of OPN staining were significantly correlated with the
      presence of lymph node metastases (P = 0.0091) and tumor size (P = 0.0001). We
      also show that treatment of human PTC cells with recombinant exogenous OPN
      stimulated Matrigel invasion and activated the ERK and V-AKT murine thymoma viral
      oncogene homolog 1/protein kinase B; signaling pathways. Blockage of anti-CD44
      antibodies prevented these effects. CONCLUSIONS: Given its prevalence and its
      correlation with aggressive features of human PTCs, we suggest that OPN might be
      used as a diagnostic and prognostic marker for these tumors. Furthermore, given
      the role of the OPN-CD44v6 axis in PTC cells, we suggest that CD44 and/or OPN may
      be molecular targets for therapeutic intervention in aggressive PTCs.

PMID- 15998774
TI  - The RsaI polymorphism in the estrogen receptor-beta gene is associated with male
      infertility.
AB  - CONTEXT: Hypospadias, cryptorchidism, testicular cancer, and low semen quality
      have been proposed as being parts of the testicular dysgenesis syndrome (TDS)
      hypothetically due to changes in the androgen-estrogen balance in utero.
      Estrogens and estrogen receptors (ERs) play a role in regulating testicular
      function. ERbeta contains two silent polymorphisms, RsaI (G1082A) and AluI
      (G1730A). OBJECTIVE: We investigated the significance of these polymorphisms in
      the etiology of disorders being part of TDS. SETTING: The patients were recruited
      consecutively through university hospital clinics. PARTICIPANTS: Four groups of
      Caucasian patients were included: 106 men from infertile couples with a sperm
      concentration less than 5 x 10(6) spermatozoa/ml, 86 testicular cancer patients,
      51 boys with hypospadias, and 23 cases with cryptorchidism. Military conscripts
      (n = 186) with sperm concentration higher than 5 x 10(6) spermatozoa/ml served as
      controls. MAIN OUTCOME MEASURES: ERbeta polymorphisms RsaI and AluI were
      determined by allele-specific PCR. In addition, reproductive hormone analyses
      were performed in controls and infertile men. RESULTS: Compared with the
      controls, the frequency of the heterozygous RsaI AG-genotype was three times
      higher in infertile men (13.2 vs. 4.3%; P = 0.01). The heterozygous RsaI AG
      genotype was associated with an approximately 20% reduction in LH concentration,
      compared with the wild-type RsaI GG genotype in both controls and infertile men.
      Subjects with testicular cancer, hypospadias, or cryptorchidism did not differ
      from controls regarding the frequency of any of the polymorphisms. CONCLUSIONS:
      Polymorphisms in ERbeta may have modulating effects on human spermatogenesis. The
      phenotype of TDS seems to be, at least partly, determined by the genotype.

PMID- 15998775
TI  - Progestin suppresses thrombin- and interleukin-1beta-induced interleukin-11
      production in term decidual cells: implications for preterm delivery.
AB  - CONTEXT: Decidual inflammation and hemorrhage are major contributors to the
      pathogenesis of preterm delivery (PTD). IL-11 is a cytokine with pleiotropic
      biological effects, including induction of T helper cell type 2 and inhibition of
      T helper cell type 1 cytokine responses. Paradoxically, it enhances the synthesis
      of prostaglandins, which induce labor. OBJECTIVE: The objectives of this study
      were to evaluate in vivo IL-11 expression in decidua after term and preterm
      deliveries and evaluate the effects of the primary mediators of inflammation, IL
      1beta and TNF-alpha, as well as the primary regulator of hemostasis, thrombin, on
      IL-11 expression in cultured term decidual cells (DCs). INTERVENTIONS AND MAIN
      OUTCOME MEASURES: Human decidua from uncomplicated term deliveries and
      chorioamnionitis- or placental abruption-related PTDs were immunostained for IL
      11. Cultures of DCs were primed with estradiol (E2) or with E2 and
      medroxyprogesterone acetate (MPA), then incubated in a defined medium with
      corresponding steroid(s) with or without IL-1beta, TNF-alpha, or thrombin. IL-11
      levels in DC-defined media were assessed by ELISA and Western blotting; IL-11
      mRNA levels were measured by quantitative RT-PCR. RESULTS: IL-11 immunostaining
      was significantly higher in DCs after PTD compared with those after term delivery
      (P < 0.05). In the absence of cytokines or thrombin, IL-11 levels in the defined
      medium were 47% lower in incubations with E2 plus MPA vs. E2 alone (P = 0.001).
      IL-1beta and thrombin elevated IL-11 output during incubations with E2 [24-fold
      (P < 0.05) and 120-fold (P < 0.05), respectively]. These increases were blunted
      by the addition of MPA [13-fold (P < 0.05) and 36-fold (P < 0.05), respectively].
      Western blot analysis confirmed the ELISA results, and RT-PCR demonstrated
      corresponding effects on IL-11 mRNA levels. Unexpectedly, TNF-alpha did not
      affect IL-11 levels. CONCLUSION: Because excess IL-1beta and thrombin generation
      are associated with chorioamnionitis- and abruption-related PTD, respectively,
      these findings add to our understanding of the genesis of inflammation- and
      abruption-associated prematurity.

PMID- 15998776
TI  - Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of
      the adenosine triphosphate-sensitive potassium channel impairing trafficking and
      function.
AB  - CONTEXT: The ATP-sensitive potassium (K(ATP)) channel, assembled from the
      inwardly rectifying potassium channel Kir6.2 and the sulfonylurea receptor 1,
      regulates insulin secretion in beta-cells. A loss of function of K(ATP) channels
      causes depolarization of beta-cells and congenital hyperinsulinism (CHI), a
      disease presenting with severe hypoglycemia in the newborn period. OBJECTIVE: Our
      objective was identification of a novel mutation in Kir6.2 in a patient with CHI
      and molecular and cell-biological analysis of the impact of this mutation. DESIGN
      AND SETTING: We combined immunohistochemistry, advanced life fluorescence
      imaging, and electrophysiology in HEK293T cells transiently transfected with
      mutant Kir6.2. PATIENT AND INTERVENTION: The patient presented with macrosomia at
      birth and severe hyperinsulinemic hypoglycemia. Despite medical treatment, the
      newborn continued to suffer from severe hypoglycemic episodes, and at 4 months of
      age subtotal pancreatectomy was performed. MAIN OUTCOME MEASURE: We assessed
      patch-clamp recordings and confocal microscopy in HEK293T cells. RESULTS: We have
      identified a homozygous missense mutation, H259R, in the Kir6.2 subunit of a
      patient with severe CHI. Coexpression of Kir6.2(H259R) with sulfonylurea receptor
      1 in HEK293T cells completely abolished K(ATP) currents in electrophysiological
      recordings. Double immunofluorescence staining revealed that mutant Kir6.2 was
      partly retained in the endoplasmic reticulum (ER) causing decreased surface
      expression as observed with total internal reflection fluorescence. Mutation of
      an ER-retention signal partially rescued the trafficking defect without restoring
      whole-cell currents. CONCLUSION: The H259R mutation of the Kir6.2 subunit results
      in a channel that is partially retained in the ER and nonfunctional upon arrival
      at the plasma membrane.

PMID- 15998777
TI  - Randomized, single blind trial of intravenous versus oral steroid monotherapy in
      Graves' orbitopathy.
AB  - CONTEXT: Glucocorticoids are effective for severe Graves' orbitopathy (GO), which
      causes substantial morbidity. The question at issue is how best to use them.
      OBJECTIVE: The objective of this study was to optimize glucocorticoid application
      in GO. DESIGN: The study design was a randomized trial over 12 wk with 6-month
      follow-up. SETTING: The study was performed at university joint thyroid and
      ophthalmic clinics. PATIENTS: Seventy euthyroid out-patients with untreated,
      active, and severe GO were studied. INTERVENTION: Patients received either once
      weekly iv methylprednisolone (0.5 g, then 0.25 g, 6 wk each) or oral prednisolone
      starting with 0.1 g/d, then tapering the dose by 0.01 g/wk. MAIN OUTCOME
      MEASURES: At 3 months, the primary end point was a composite of improvements in
      proptosis, lid fissure width, and rate of diplopia in primary gaze, visual
      acuity, eye muscle thickness, and patient's quality of life. RESULTS: Intravenous
      glucocorticoid therapy resulted in rapid, significant, and sustained improvement.
      At 3 months, 27 of 35 patients (77%) in the iv group had a treatment response
      compared with 18 of 35 (51%) in the oral group (P < 0.01). Improvements over
      baseline values for disease severity (e.g. visual acuity; P = 0.01) and activity
      (e.g. chemosis; P < 0.01) and for quality of life (P < 0.001) were greater in the
      iv group. TSH receptor antibody titers decreased during iv steroid administration
      (P < 0.001), and smoking had a strong impact on the therapy response (P < 0.001).
      Additional treatment was required less frequently in the iv group. Intravenous
      steroids were safe, with different rates of adverse events between the two groups
      (P < 0.001). CONCLUSIONS: In patients with active and severe GO, iv
      glucocorticoids were more effective and better tolerated than oral steroids.

PMID- 15998778
TI  - Morphological and immunohistochemical differences between gonadal maturation
      delay and early germ cell neoplasia in patients with undervirilization syndromes.
AB  - CONTEXT: Maturation delay of germ cells and their progression into carcinoma in
      situ (CIS) frequently occurs in intersex patients. A developmentally delayed germ
      cell resembles a CIS cell and displays prolonged expression of
      immunohistochemical markers used for the diagnosis of CIS. This questions their
      applicability in young children. OBJECTIVE: The objective of the study was the
      elaboration of tools to distinguish germ cells with maturation delay and CIS.
      DESIGN: The design was a qualitative and quantitative analysis of the expression
      of diagnostic markers for CIS in gonads of young patients with undervirilization
      syndromes. SETTING: The study was conducted in the pathology department of a
      university center, specializing in germ cell tumor pathogenesis. PATIENTS: Fifty
      eight formalin-fixed, paraffin-embedded testicular tissue samples of 30
      undervirilized patients (1 month to 23 yr of age) were analyzed. INTERVENTIONS:
      INTERVENTIONS included hematoxylin-eosin staining, immunohistochemistry for
      octamer binding transcription factor (OCT)3/4, gene encoding the stem cell factor
      receptor that has tyrosine kinase activity c-KIT, placental/germ alkaline
      phosphatase (PLAP), testis-specific protein Y encoded (TSPY), and VASA, double
      staining for OCT3/4 and VASA, with ploidy determination by fluorescent in situ
      hybridization. MAIN OUTCOME MEASURE: Maturation delay and CIS are characterized
      by the staining patterns of the immunohistochemical markers. RESULTS: CIS was
      diagnosed in three of 30 patients (10%) and four of 58 gonads (6.9%). Patient
      age, distribution of OCT3/4-positive cells throughout the gonad, and their
      position within the seminiferous tubule differ between maturation delay and CIS.
      Abnormal OCT3/4 and testis-specific protein Y encoded expression appear to be of
      pathogenetic relevance in the development of these lesions. CONCLUSION: The
      dimorphic expression of OCT3/4 allows distinction between maturation delay and
      CIS. Studies in larger patient series are essential before a biopsy to evaluate
      the neoplastic risk can eventually be proposed as an alternative for gonadectomy.

PMID- 15998779
TI  - A novel homozygous Ala529Val LMNA mutation in Turkish patients with
      mandibuloacral dysplasia.
AB  - CONTEXT: Mandibuloacral dysplasia (MAD) is a phenotypically heterogeneous, rare
      autosomal recessive disorder characterized by mandibular and clavicular
      hypoplasia, acroosteolysis, delayed closure of cranial sutures, joint
      contractures, lipodystrophy, and mottled cutaneous pigmentation. MAD patients
      with type A lipodystrophy with loss of sc fat from the extremities and normal or
      slight excess in the neck and truncal regions have been previously reported to
      carry a homozygous Arg527His mutation in LMNA (Lamin A/C) gene. Among those with
      type B pattern of lipodystrophy with generalized loss of sc fat, we recently
      reported a patient carrying compound heterozygous mutations in an endoprotease,
      zinc metalloproteinase (ZMPSTE24), gene that is involved in posttranslational
      processing of prelamin A to mature lamin A. OBJECTIVE: Our objective was to carry
      out mutational analysis of LMNA in additional patients with MAD and type A
      lipodystrophy. DESIGN AND SETTING: We studied descriptive case reports at a
      referral center. PATIENTS: Subjects were a male and a female patient with MAD who
      belonged to two pedigrees from Turkey. MAIN OUTCOME MEASURES: We assessed
      genotype-phenotype relationships. RESULTS: We now report that both these patients
      have a novel homozygous missense mutation (c.1586C-->T; c refers to cDNA
      reference sequence) in LMNA that replaces a well-conserved residue alanine at
      position 529 to valine. Intragenic single-nucleotide polymorphisms revealed a
      common haplotype spanning 2.5 kb around the mutated nucleotide in the parents of
      both the affected subjects, suggesting ancestral origin of the mutation. The
      female patient had no breast development despite normal menstruation, a phenotype
      different from that seen in women with MAD and Arg527His LMNA mutation.
      CONCLUSIONS: We conclude that two homozygous missense LMNA mutations involving
      the arginine 527 and alanine 529 residues cause MAD with subtle variations in
      phenotype.

PMID- 15998780
TI  - Efficacy and safety results of long-term growth hormone treatment of idiopathic
      short stature.
AB  - CONTEXT: Small clinical trials of GH treatment of idiopathic short stature (ISS)
      show variable efficacy. OBJECTIVE: The study was an analysis of a large GH
      registry for efficacy and safety of GH treatment of ISS. There was also a
      comparison with a specific clinical trial. DESIGN: Up to 7 yr of GH treatment of
      ISS was evaluated for efficacy and safety in the National Cooperative Growth
      Study (NCGS). SETTING: The NCGS study was conducted at Genentech, Inc. and
      included 47,226 patients. PATIENTS: The ISS group included maximum stimulated GH
      10 ng/ml or more and/or a report of ISS by investigator (n = 8018; all included
      for safety). Cohort 1 (n = 2520) was similar to the clinical trial, cohort 2 (n =
      283) included subjects younger than 5 yr of age, and cohort 3 (n = 940) was
      pubertal at GH start. INTERVENTION: GH, approximately 0.30 mg/kg.wk, was given.
      MAIN OUTCOME MEASURES: These included growth velocities and height sd (HtSDS).
      RESULTS: Mean first-year growth velocities in cohorts 1, 2, and 3 increased 4.6,
      3.9, and 4.4 cm/yr over pretreatment, respectively. Measures included: baseline
      mean HtSDS, -2.9, -3.2, and -2.8; mean HtSDS at 1 yr, -2.4, -2.3, and -2.3,
      respectively. Mean HtSDS after 7 yr in cohorts 1 (n = 303) and 2 (n = 85) and 5
      yr in cohort 3 (n = 58) were: -1.2, -1.0, and -1.5, respectively. Cohort 3
      shorter treatment time was due to advanced baseline age (mean 13.8 yr) and
      puberty. Mean HtSDS gain in cohort 1 was comparable with the clinical trial. No
      new safety signals specific to the NCGS ISS population were observed. CONCLUSION:
      ISS patients in the GH registry demonstrate a significant increase in HtSDS with
      the safety profile similar to GH-deficient patients. RESULTS were similar to the
      clinical trial.

PMID- 15998781
TI  - High prevalence and possible de novo formation of BRAF mutation in metastasized
      papillary thyroid cancer in lymph nodes.
AB  - CONTEXT: The role of the T1799A BRAF mutation in lymph node metastasis of
      papillary thyroid cancer (PTC) is not clear. OBJECTIVE: Our objective was to
      explore the relationship between BRAF mutation and lymph node metastasis of PTC
      by examining the mutation in both the primary tumors and their paired lymph node
      metastases. DESIGN: We isolated genomic DNA from primary thyroid tumors and
      paired lymph node metastases and performed direct sequencing of exon 15 of the
      BRAF gene mutation that carries the T1799A mutation. RESULTS: In a series of 33
      cases, 21 harbored the T1799A mutation in the primary tumors, and 17 (81%) of
      them harbored the same mutation also in the paired lymph node metastases. Twelve
      cases did not harbor the T1799A mutation in the primary tumors, among which nine
      cases also did not harbor BRAF mutation in the lymph node-metastasized tumors,
      whereas the other three did harbor the T1799A mutation in lymph node-metastasized
      tumor tissues. A novel tandem TG1799-1800AA mutation within one allele was found
      in a lymph node-metastasized tumor but not in the primary tumor. This mutation
      results in the change of codon 600 (GTG) of the gene to GAA with the consequent
      amino acid change (V600E) in the B-type Raf (BRAF) protein, same as that caused
      by the T1799A mutation alone. CONCLUSION: The high prevalence of BRAF mutation in
      lymph node-metastasized PTC tissues from BRAF mutation-positive primary tumors
      and the possible de novo formation of BRAF mutation in lymph node-metastasized
      PTC were consistent with a role of BRAF mutation in facilitating the metastasis
      and progression of PTC in lymph nodes.

PMID- 15998782
TI  - Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation
      identified in patients with pituitary defects.
AB  - CONTEXT: Pituitary development depends on the actions of a large number of
      transcription factors. Among them, LHX4 is believed to play a crucial role, as
      suggested by the dominantly inherited GH deficiency associated with the recently
      identified LHX4 mutation, although the precise mechanism underlying this
      phenotype is still to be elucidated. OBJECTIVE: The objective of this study was
      to gain insight into both the function of LHX4 and the pathophysiology of the
      LHX4-related syndrome. We sought potential targets of this factor and assessed
      the abilities of various recombinant LHX4 isoforms expressed in Chinese hamster
      ovary cells to bind to and activate the POUI1F1 upstream regulatory sequence.
      RESULTS: We show that normal LHX4 binds to a human-specific element and
      subsequently activates transcription from the proximal upstream regulatory
      sequence of POUIF1, a gene encoding a POU homeodomain transcription factor known
      as the main regulator of GH expression. As shown in this cell system, the mutant
      LHX4 proteins predicted by the defect identified in patients fail to bind to and
      subsequently activate the POU1F1 regulatory sequence, but do not impair the
      ability of normal LHX4 to activate this target. CONCLUSIONS: Such findings are
      consistent with the existence, in humans, of an LHX4-driven pathway leading to
      the expression of GH through transcriptional activation of POU1F1. They argue
      against a dominant-negative effect of the mutant LHX4 proteins over normal LHX4.
      Finally, they provide a clear-cut evaluation of the functional consequences, at
      the molecular level, of the LHX4 mutation, which, through disruption of the
      former pathway, would account for one key feature of the LHX4-related syndrome.

PMID- 15998783
TI  - A role for pancreatic polypeptide in the regulation of gastric emptying and short
      term metabolic control.
AB  - CONTEXT: Previous studies using pancreatic polypeptide (PP) infusions in humans
      have failed to show an effect on gastric emptying, glucose metabolism, and
      insulin secretion. This might be due to the use of nonhuman sequences of the
      peptide. OBJECTIVE: The objective of this study was to use synthetic human PP to
      study gastric emptying rates of a solid meal and postprandial hormone secretion
      and glucose disposal as well as the gastric emptying rate of water. DESIGN: This
      was a single-blind study. SETTING: The study was performed at a university
      hospital. PARTICIPANTS: Fourteen healthy adult subjects were studied.
      INTERVENTIONS: Infusion of saline or PP at 0.75 or 2.25 pmol/kg.min was given to
      eight subjects (gastric emptying of solid food), and infusion of saline or PP at
      2.25 pmol/kg.min was given to six subjects (gastric emptying of water). MAIN
      OUTCOME MEASURES: The main outcome measures were gastric emptying of solids
      (scintigraphy), hunger ratings (visual analog scale), and plasma concentrations
      of PP, insulin, glucagon, somatostatin, glucagon-like peptide 1, glucose, and
      gastric emptying of plain water (scintigraphy). RESULTS: PP prolonged the lag
      phase and the half-time of emptying of the solid meal. The change in hunger
      rating, satiety, desire to eat after the meal, or prospective consumption was not
      affected. The postprandial rise in plasma glucose was prolonged by PP. The
      postprandial rise in insulin was also delayed by PP. PP had no significant effect
      on the emptying of water. CONCLUSIONS: PP inhibits gastric emptying of solid food
      and delays the postprandial rise in plasma glucose and insulin. PP is suggested
      to have a physiological role in the pancreatic postprandial counterregulation of
      gastric emptying and insulin secretion.

PMID- 15998784
TI  - The role of intramyocellular lipids during hypoglycemia in patients with
      intensively treated type 1 diabetes.
AB  - CONTEXT: Endocrine defensive mechanisms provide for energy supply during
      hypoglycemia. Intramyocellular lipids (IMCL) were recently shown to contribute to
      energy supply during exercise. OBJECTIVE: The objective of this study was to
      assess the contribution of IMCL compared with lipolysis and endogenous glucose
      production (EGP) to insulin-mediated hypoglycemia counterregulation in patients
      with type 1 diabetes mellitus (T1DM). DESIGN AND SETTING: This was a prospective
      explorative study performed in a university research facility. PARTICIPANTS: Six
      well-controlled T1DM (age, 29 +/- 4 yr; body mass index, 23.4 +/- 1.0 kg/m2;
      hemoglobin A1c, 6.3 +/- 0.1%) and six nondiabetic humans (controls; age, 28 +/- 2
      yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 5.1 +/- 0.1%) were
      studied. INTERVENTIONS: We performed 240-min hypoglycemic (approximately 3 mM)
      hyperinsulinemic (0.8 mU/kg x min) clamps on separate days to measure: 1)
      systemic lipolysis ([2H5]glycerol turnover), EGP ([6,6-(2)H2]glucose), and local
      lipolysis in abdominal s.c. adipose tissue and gastrocnemius muscle
      (microdialysis); and 2) IMCL (by 1H nuclear magnetic resonance spectroscopy) in
      soleus and tibialis anterior muscle. MAIN OUTCOME MEASURES: The main outcome
      measures were changes in IMCL during prolonged hypoglycemia. RESULTS: At
      baseline, EGP, glycerol turnover, and IMCL were not different between the groups.
      During hypoglycemia, hormonal counterregulation was blunted in T1DM (peak:
      glucagon, 68 +/- 4 vs. 170 +/- 37 pg/ml; cortisol, 16 +/- 2 vs. 24 +/- 2
      microg/dl; epinephrine, 274 +/- 84 vs. 597 +/- 212 pg/ml; all P < 0.05 vs.
      control). T1DM had approximately 50% lower EGP (4.6 +/- 0.6 vs. 10.9 +/- 0.5
      micromol/kg x min; P < 0.005), but approximately 40% higher glycerol turnover
      (374 +/- 21 vs. 272 +/- 19 micromol/kg x min; P < 0.01). Glycerol concentrations
      in muscle (T1DM, 302 +/- 22 control, 346 +/- 17 micromol/liter) and adipose
      tissue (264 +/- 25 vs. 318 +/- 25 micromol/liter) did not differ between groups.
      IMCL in soleus and tibialis anterior muscle did not change from baseline during
      hypoglycemia. CONCLUSIONS: In well-controlled T1DM, impaired hypoglycemia
      counterregulation is associated with decreased glucose production and augmented
      whole body lipolysis, which cannot be explained by either hydrolysis of muscle
      triglycerides or increased abdominal s.c. adipose tissue lipolysis.

PMID- 15998785
TI  - Dietary calcium intake protects women consuming oral contraceptives from spine
      and hip bone loss.
AB  - CONTEXT: It is estimated that 80% of all women have used oral contraceptives
      (OCP), but OCP use may prevent attainment of maximal peak bone mass in young
      women and thus increase the risk of osteoporosis later in life. OBJECTIVE: This
      study examined whether increased calcium intake could reduce the detrimental
      effects of OCP use on bone mass in young women. DESIGN: The study design was a 1
      yr intervention. SETTING: The study was performed in a general community setting.
      SUBJECTS: One hundred fifty-four young (18-30 yr old) healthy women with a
      dietary calcium intake of less than 800 mg/d began the study, and 135 completed
      the trial. INTERVENTION: Subjects were randomly assigned to one of three diet
      intervention groups: 1) control, continuous established (<800 mg/d) dietary
      calcium intake; 2) medium dairy, increase calcium intake to approximately 1000
      1100 mg/d; and 3) high dairy, increase calcium intake to approximately 1200-1300
      mg/d. Randomization was stratified by OCP use. MAIN OUTCOME MEASURES: The main
      outcome measures were total body bone mineral density (BMD) and content (BMC);
      total hip BMD, BMC, and bone area; and spine BMD, BMC, and bone area. RESULTS:
      Dairy product intervention positively impacted the percentage change in total hip
      BMD and BMC. In addition, dairy product intake prevented a negative percentage
      change in total hip and spine BMD in OCP users. CONCLUSION: Dairy product intake,
      at levels necessary to achieve the recommended intakes of calcium, protected the
      total hip BMD and spine BMD from loss observed in young healthy women with low
      calcium intakes who were using OCP.

PMID- 15998786
TI  - Dendritic cells star in Vancouver.
AB  - The fast-moving field of dendritic cell (DC) biology is hard to keep pace with.
      Here we report on advances from the recent Keystone Symposium, "Dendritic Cells
      at the Center of Innate and Adaptive Immunity," organized in Vancouver, BC on
      Feb. 1-7, 2005 by Anne O'Garra, Jacques Banchereau, and Alan Sher. New insights
      into the molecular mechanisms of DC function and their influence on immune
      regulation, their role in infectious and autoimmune disease, and new clinical
      applications are highlighted.

PMID- 15998787
TI  - Disruption of Nrf2 enhances susceptibility to severe airway inflammation and
      asthma in mice.
AB  - Oxidative stress has been postulated to play an important role in the
      pathogenesis of asthma; although a defect in antioxidant responses has been
      speculated to exacerbate asthma severity, this has been difficult to demonstrate
      with certainty. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox
      sensitive basic leucine zipper transcription factor that is involved in the
      transcriptional regulation of many antioxidant genes. We show that disruption of
      the Nrf2 gene leads to severe allergen-driven airway inflammation and
      hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin
      sensitization and challenge in Nrf2-disrupted mice was associated with more
      pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs
      than seen in wild-type littermates. Nrf2 disruption resulted in an increased
      expression of the T helper type 2 cytokines interleukin (IL)-4 and IL-13 in
      bronchoalveolar lavage fluid and in splenocytes after allergen challenge. The
      enhanced severity of the asthmatic response from disruption of the Nrf2 pathway
      was a result of a lowered antioxidant status of the lungs caused by lower basal
      expression, as well as marked attenuation, of the transcriptional induction of
      multiple antioxidant genes. Our studies suggest that the responsiveness of Nrf2
      directed antioxidant pathways may act as a major determinant of susceptibility to
      allergen-mediated asthma.

PMID- 15998788
TI  - alpha v beta3-dependent cross-presentation of matrix metalloproteinase-2 by
      melanoma cells gives rise to a new tumor antigen.
AB  - A large array of antigens that are recognized by tumor-specific T cells has been
      identified and shown to be generated through various processes. We describe a new
      mechanism underlying T cell recognition of melanoma cells, which involves the
      generation of a major histocompatibility complex class I-restricted epitope after
      tumor-mediated uptake and processing of an extracellular protein--a process
      referred to as cross-presentation-which is believed to be restricted to immune
      cells. We show that melanoma cells cross-present, in an alpha v beta3-dependent
      manner, an antigen derived from secreted matrix metalloproteinase-2 (MMP-2) to
      human leukocyte antigen A*0201-restricted T cells. Because MMP-2 activity is
      critical for melanoma progression, the MMP-2 peptide should be cross-presented by
      most progressing melanomas and represents a unique antigen for vaccine therapy of
      these tumors.

PMID- 15998789
TI  - Restricted MHC-peptide repertoire predisposes to autoimmunity.
AB  - MHC molecules associated with autoimmunity possess known structural features that
      limit the repertoire of peptides that they can present. Such limitation gives a
      selective advantage to TCRs that rely on interaction with the MHC itself, rather
      than with the peptide residues. At the same time, negative selection is impaired
      because of the lack of negatively selecting peptide ligands. The combination of
      these factors may predispose to autoimmunity. We found that mice with an MHC
      class II-peptide repertoire reduced to a single complex demonstrated various
      autoimmune reactions. Transgenic mice bearing a TCR (MM14.4) cloned from such a
      mouse developed severe autoimmune dermatitis. Although MM14.4 originated from a
      CD4+ T cell, dermatitis was mediated by CD8+ T cells. It was established that
      MM14.4+ is a highly promiscuous TCR with dual MHC class I/MHC class II
      restriction. Furthermore, mice with a limited MHC-peptide repertoire selected
      elevated numbers of TCRs with dual MHC class I/MHC class II restriction, a likely
      source of autoreactivity. Our findings may help to explain the link between MHC
      class I responses that are involved in major autoimmune diseases and the well
      established genetic linkage of these diseases with MHC class II.

PMID- 15998790
TI  - BLT1-mediated T cell trafficking is critical for rejection and obliterative
      bronchiolitis after lung transplantation.
AB  - Leukotriene B4 is a lipid mediator that recently has been shown to have potent
      chemotactic activity for effector T lymphocytes mediated through its receptor,
      BLT1. Here, we developed a novel murine model of acute lung rejection to
      demonstrate that BLT1 controls effector CD8+ T cell trafficking into the lung and
      that disruption of BLT1 signaling in CD8+ T cells reduces lung inflammation and
      mortality in the model. In addition, we used BLT1-deficient mice and a BLT1
      antagonist in two tracheal transplant models of lung transplantation to
      demonstrate the importance of BLT1 for the recruitment of T cells into tracheal
      allografts. We also show that BLT1-mediated CD8+ T cell recruitment plays an
      important role in the development of airway fibroproliferation and obliteration.
      Finally, in human studies of lung transplant recipients, we found that BLT1 is up
      regulated on T lymphocytes isolated from the airways of patients with
      obliterative bronchiolitis. These data demonstrate that BLT1 contributes to the
      development of lung rejection and obliterative bronchiolitis by mediating
      effector T lymphocyte trafficking into the lung. This is the first report that
      describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease
      and identifies BLT1 as a potential therapeutic target after lung transplantation.

PMID- 15998791
TI  - The timing of TCR alpha expression critically influences T cell development and
      selection.
AB  - Sequential rearrangement of the T cell receptor for antigen (TCR) beta and alpha
      chains is a hallmark of thymocyte development. This temporal control is lost in
      TCR transgenics because the alpha chain is expressed prematurely at the CD4- CD8-
      double negative (DN) stage. To test the importance of this, we expressed the HY
      alpha chain at the physiological CD4+ CD8+ double positive (DP) stage. The
      reduced DP and increased DN cellularity typically seen in TCR transgenics was not
      observed when the alpha chain was expressed at the appropriate stage.
      Surprisingly, antigen-driven selection events were also altered. In male mice,
      thymocyte deletion now occurred at the single positive or medullary stage. In
      addition, no expansion of CD8 alpha alpha intestinal intraepithelial lymphocytes
      (IELs) was observed, despite the fact that HY transgenics have been used to model
      IEL development. Collectively, these data establish the importance of proper
      timing of TCR expression in thymic development and selection and emphasize the
      need to use models that most accurately reflect the physiologic process.

PMID- 15998792
TI  - Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha
      production.
AB  - Psoriasis is one of the most common T cell-mediated autoimmune diseases in
      humans. Although a role for the innate immune system in driving the autoimmune T
      cell cascade has been proposed, its nature remains elusive. We show that
      plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-alpha
      producing cells, infiltrate the skin of psoriatic patients and become activated
      to produce IFN-alpha early during disease formation. In a xenograft model of
      human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting
      the ability of PDCs to produce IFN-alpha prevented the T cell-dependent
      development of psoriasis. Furthermore, IFN-alpha reconstitution experiments
      demonstrated that PDC-derived IFN-alpha is essential to drive the development of
      psoriasis in vivo. These findings uncover a novel innate immune pathway for
      triggering a common human autoimmune disease and suggest that PDCs and PDC
      derived IFN-alpha represent potential early targets for the treatment of
      psoriasis.

PMID- 15998793
TI  - Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves
      functional recovery after spinal cord injury.
AB  - In the central nervous system (CNS), the transcription factor nuclear factor (NF)
      kappaB is a key regulator of inflammation and secondary injury processes. After
      trauma or disease, the expression of NF-kappaB-dependent genes is highly
      activated, leading to both protective and detrimental effects on CNS recovery. We
      demonstrate that selective inactivation of astroglial NF-kappaB in transgenic
      mice expressing a dominant negative (dn) form of the inhibitor of kappaB alpha
      under the control of an astrocyte-specific promoter (glial fibrillary acidic
      protein [GFAP]-dn mice) leads to a dramatic improvement in functional recovery 8
      wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit
      reduced lesion volume and substantially increased white matter preservation. In
      parallel, they show reduced expression of proinflammatory chemokines and
      cytokines, such as CXCL10, CCL2, and transforming growth factor-beta2, and of
      chondroitin sulfate proteoglycans participating in the formation of the glial
      scar. We conclude that selective inhibition of NF-kappaB signaling in astrocytes
      results in protective effects after SCI and propose the NF-kappaB pathway as a
      possible new target for the development of therapeutic strategies for the
      treatment of SCI.

PMID- 15998794
TI  - Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and
      p27 Kip1 degradation.
AB  - Cyclin-dependent kinase inhibitors (CKIs) and Notch receptor activation have been
      shown to influence adult stem cells and progenitors by altering stem cell self
      renewal and proliferation. Yet, no interaction between these molecular pathways
      has been defined. Here we show that ligand-independent and ligand-dependent
      activation of Notch1 induces transcription of the S phase kinase-associated
      protein 2 (SKP2), the F-box subunit of the ubiquitin-ligase complex SCF(SKP2)
      that targets proteins for degradation. Up-regulation of SKP2 by Notch signaling
      enhances proteasome-mediated degradation of the CKIs, p27 Kip1 and p21 Cip1, and
      causes premature entry into S phase. Silencing of SKP2 by RNA interference in G1
      stabilizes p27 Kip1 and p21 Cip1 and abolishes Notch effect on G1-S progression.
      Thus, SKP2 serves to link Notch1 activation with the cell cycle machinery. This
      novel pathway involving Notch/SKP2/CKIs connects a cell surface receptor with
      proximate mediators of cell cycle activity, and suggests a mechanism by which a
      known physiologic mediator of cell fate determination interfaces with cell cycle
      control.

PMID- 15998795
TI  - Selective activation of STAT5 unveils its role in stem cell self-renewal in
      normal and leukemic hematopoiesis.
AB  - Although the concept of a leukemic stem cell system has recently been well
      accepted, its nature and the underlying molecular mechanisms remain obscure.
      Constitutive activation of signal transducers and activators of transcription 3
      (STAT3) and STAT5 is frequently detected in various hematopoietic tumors. To
      evaluate their role in normal and leukemic stem cells, we took advantage of
      constitutively active STAT mutants to activate STAT signaling selectively in
      hematopoietic stem cells (HSCs). Activation of STAT5 in CD34- c-Kit+ Sca-1+
      lineage marker- (CD34- KSL) HSCs led to a drastic expansion of multipotential
      progenitors and promoted HSC self-renewal ex vivo. In sharp contrast, STAT3 was
      demonstrated to be dispensable for the HSC maintenance in vivo, and its
      activation facilitated lineage commitment of HSCs in vitro. In a mouse model of
      myeloproliferative disease (MPD), sustained STAT5 activation in CD34- KSL HSCs
      but not in CD34+ KSL multipotential progenitors induced fatal MPD, indicating
      that the capacity of STAT5 to promote self-renewal of hematopoietic stem cells is
      crucial to MPD development. Our findings collectively establish a specific role
      for STAT5 in self-renewal of normal as well as leukemic stem cells.

PMID- 15998796
TI  - Regulation of natural cytotoxicity by the adaptor SAP and the Src-related kinase
      Fyn.
AB  - SAP is an adaptor protein that is expressed in NK and T cells. It is mutated in
      humans who have X-linked lymphoproliferative (XLP) disease. By interacting with
      SLAM family receptors, SAP enables tyrosine phosphorylation signaling of these
      receptors by its ability to recruit the Src-related kinase, Fyn. Here, we
      analyzed the role of SAP in NK cell functions using the SAP-deficient mouse
      model. Our results showed that SAP was required for the ability of NK cells to
      eliminate tumor cells in vitro and in vivo. This effect strongly correlated with
      expression of CD48 on tumor cells, the ligand of 2B4, a SLAM-related receptor
      expressed in NK cells. In keeping with earlier reports that studied human NK
      cells, we showed that SAP was necessary for the ability of 2B4 to trigger
      cytotoxicity and IFN-gamma secretion. In the absence of SAP, 2B4 function was
      shifted toward inhibition of NK cell-mediated cytotoxicity. By analyzing mice
      lacking Fyn, we showed that similarly to SAP, Fyn was strictly required for 2B4
      function. Taken together, these results provide evidence that the 2B4-SAP-Fyn
      cascade defines a potent activating pathway of natural cytotoxicity. They also
      could help to explain the high propensity of patients who have XLP disease to
      develop lymphoproliferative disorders.

PMID- 15998797
TI  - Membrane recruitment of NOD2 in intestinal epithelial cells is essential for
      nuclear factor-{kappa}B activation in muramyl dipeptide recognition.
AB  - Nucleotide oligomerization domain (NOD) 2 functions as a mammalian cytosolic
      pathogen recognition molecule, and mutant forms have been genetically linked to
      Crohn's disease (CD). NOD2 associates with the caspase activation and recruitment
      domain of RIP-like interacting caspase-like apoptosis regulatory protein kinase
      (RICK)/RIP2 and activates nuclear factor (NF)-kappaB in epithelial cells and
      macrophages, whereas NOD2 mutant 3020insC, which is associated with CD, shows an
      impaired ability to activate NF-kappaB. To gain insight into the molecular
      mechanisms of NOD2 function, we performed a functional analysis of deletion and
      substitution NOD2 mutants. NOD2, but not NOD2 3020insC mutant, associated with
      cell surface membranes of intestinal epithelial cells. Membrane targeting and
      subsequent NF-kappaB activation are mediated by two leucine residues and a
      tryptophan-containing motif in the COOH-terminal domain of NOD2. The membrane
      targeting of NOD2 is required for NF-kappaB activation after the recognition of
      bacterial muramyl dipeptide in intestinal epithelial cells.

PMID- 15998798
TI  - Calreticulin signals upstream of calcineurin and MEF2C in a critical Ca(2+)
      dependent signaling cascade.
AB  - We uncovered a new pathway of interplay between calreticulin and myocyte-enhancer
      factor (MEF) 2C, a cardiac-specific transcription factor. We establish that
      calreticulin works upstream of calcineurin and MEF2C in a Ca(2+)-dependent signal
      transduction cascade that links the endoplasmic reticulum and the nucleus during
      cardiac development. In the absence of calreticulin, translocation of MEF2C to
      the nucleus is compromised. This defect is reversed by calreticulin itself or by
      a constitutively active form of calcineurin. Furthermore, we show that expression
      of the calreticulin gene itself is regulated by MEF2C in vitro and in vivo and
      that, in turn, increased expression of calreticulin affects MEF2C transcriptional
      activity. The present findings provide a clear molecular explanation for the
      embryonic lethality observed in calreticulin-deficient mice and emphasize the
      importance of calreticulin in the early stages of cardiac development. Our study
      illustrates the existence of a positive feedback mechanism that ensures an
      adequate supply of releasable Ca(2+) is maintained within the cell for activation
      of calcineurin and, subsequently, for proper functioning of MEF2C.

PMID- 15998799
TI  - Dissociation of Akt1 from its negative regulator JIP1 is mediated through the
      ASK1-MEK-JNK signal transduction pathway during metabolic oxidative stress: a
      negative feedback loop.
AB  - We have previously observed that metabolic oxidative stress-induced death domain
      associated protein (Daxx) trafficking is mediated by the ASK1-SEK1-JNK1-HIPK1
      signal transduction pathway. The relocalized Daxx from the nucleus to the
      cytoplasm during glucose deprivation participates in a positive regulatory
      feedback loop by binding to apoptosis signal-regulating kinase (ASK) 1. In this
      study, we report that Akt1 is involved in a negative regulatory feedback loop
      during glucose deprivation. Akt1 interacts with c-Jun NH(2)-terminal kinase (JNK)
      interacting protein (JIP) 1, and Akt1 catalytic activity is inhibited. The JNK2
      mediated phosphorylation of JIP1 results in the dissociation of Akt1 from JIP1
      and subsequently restores Akt1 enzyme activity. Concomitantly, Akt1 interacts
      with stress-activated protein kinase/extracellular signal-regulated kinase (SEK)
      1 (also known as MKK4) and inhibits SEK1 activity. Knockdown of SEK1 leads to the
      inhibition of JNK activation, JIP1-JNK2 binding, and the dissociation of Akt1
      from JIP1 during glucose deprivation. Knockdown of JIP1 also leads to the
      inhibition of JNK activation, whereas the knockdown of Akt1 promotes JNK
      activation during glucose deprivation. Altogether, our data demonstrate that Akt1
      participates in a negative regulatory feedback loop by interacting with the JIP1
      scaffold protein.

PMID- 15998800
TI  - Hydrogen peroxide regulation of endothelial exocytosis by inhibition of N
      ethylmaleimide sensitive factor.
AB  - Although an excess of reactive oxygen species (ROS) can damage the vasculature,
      low concentrations of ROS mediate intracellular signal transduction pathways. We
      hypothesized that hydrogen peroxide plays a beneficial role in the vasculature by
      inhibiting endothelial exocytosis that would otherwise induce vascular
      inflammation and thrombosis. We now show that endogenous H(2)O(2) inhibits
      thrombin-induced exocytosis of granules from endothelial cells. H(2)O(2)
      regulates exocytosis by inhibiting N-ethylmaleimide sensitive factor (NSF), a
      protein that regulates membrane fusion events necessary for exocytosis. H(2)O(2)
      decreases the ability of NSF to hydrolyze adenosine triphosphate and to
      disassemble the soluble NSF attachment protein receptor complex. Mutation of NSF
      cysteine residue C264T eliminates the sensitivity of NSF to H(2)O(2), suggesting
      that this cysteine residue is a redox sensor for NSF. Increasing endogenous
      H(2)O(2) levels in mice decreases exocytosis and platelet rolling on venules in
      vivo. By inhibiting endothelial cell exocytosis, endogenous H(2)O(2) may protect
      the vasculature from inflammation and thrombosis.

PMID- 15998801
TI  - A microtubule-dependent zone of active RhoA during cleavage plane specification.
AB  - Cytokinesis in animal cells results from the assembly and constriction of a
      circumferential array of actin filaments and myosin-2. Microtubules of the
      mitotic apparatus determine the position at which the cytokinetic actomyosin
      array forms, but the molecular mechanisms by which they do so remain unknown. The
      small GTPase RhoA has previously been implicated in cytokinesis. Using four
      dimensional microscopy and a probe for active RhoA, we show that active RhoA
      concentrates in a precisely bounded zone before cytokinesis and is independent of
      actin assembly. Cytokinetic RhoA activity zones are common to four echinoderm
      species, the vertebrate Xenopus laevis, and the highly asymmetric cytokinesis
      accompanying meiosis. Microtubules direct the formation and placement of the RhoA
      activity zone, and the zone is repositioned after physical spindle displacement.
      We conclude that microtubules specify the cytokinetic apparatus via a dynamic
      zone of local RhoA activity.

PMID- 15998802
TI  - Proteomic analysis of a eukaryotic cilium.
AB  - Cilia and flagella are widespread cell organelles that have been highly conserved
      throughout evolution and play important roles in motility, sensory perception,
      and the life cycles of eukaryotes ranging from protists to humans. Despite the
      ubiquity and importance of these organelles, their composition is not well known.
      Here we use mass spectrometry to identify proteins in purified flagella from the
      green alga Chlamydomonas reinhardtii. 360 proteins were identified with high
      confidence, and 292 more with moderate confidence. 97 out of 101 previously known
      flagellar proteins were found, indicating that this is a very complete dataset.
      The flagellar proteome is rich in motor and signal transduction components, and
      contains numerous proteins with homologues associated with diseases such as
      cystic kidney disease, male sterility, and hydrocephalus in humans and model
      vertebrates. The flagellum also contains many proteins that are conserved in
      humans but have not been previously characterized in any organism. The results
      indicate that flagella are far more complex than previously estimated.

PMID- 15998803
TI  - Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent
      microtubule-dependent translocation of granules to the plasma membrane.
AB  - The aggregation of high affinity IgE receptors (Fcepsilon receptor I
      [FcepsilonRI]) on mast cells is potent stimulus for the release of inflammatory
      and allergic mediators from cytoplasmic granules. However, the molecular
      mechanism of degranulation has not yet been established. It is still unclear how
      FcepsilonRI-mediated signal transduction ultimately regulates the reorganization
      of the cytoskeleton and how these events lead to degranulation. Here, we show
      that FcepsilonRI stimulation triggers the formation of microtubules in a manner
      independent of calcium. Drugs affecting microtubule dynamics effectively
      suppressed the FcepsilonRI-mediated translocation of granules to the plasma
      membrane and degranulation. Furthermore, the translocation of granules to the
      plasma membrane occurred in a calcium-independent manner, but the release of
      mediators and granule-plasma membrane fusion were completely dependent on
      calcium. Thus, the degranulation process can be dissected into two events: the
      calcium-independent microtubule-dependent translocation of granules to the plasma
      membrane and calcium-dependent membrane fusion and exocytosis. Finally, we show
      that the Fyn/Gab2/RhoA (but not Lyn/SLP-76) signaling pathway plays a critical
      role in the calcium-independent microtubule-dependent pathway.

PMID- 15998804
TI  - Aberrant lysosomal carbohydrate storage accompanies endocytic defects and
      neurodegeneration in Drosophila benchwarmer.
AB  - Lysosomal storage is the most common cause of neurodegenerative brain disease in
      preadulthood. However, the underlying cellular mechanisms that lead to neuronal
      dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer
      (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in
      yolk spheres during oogenesis and results in widespread accumulation of enlarged
      lysosomal and late endosomal inclusions. At the bnch larval neuromuscular
      junction, we observe similar inclusions and find defects in synaptic vesicle
      recycling at the level of endocytosis. In addition, loss of bnch slows endosome
      to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe
      age-dependent synaptic dysfunction and neuronal degeneration. Finally, we find
      that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner.
      We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to
      endocytic defects with functional consequences in synaptic strength, neuronal
      viability, and tau neurotoxicity.

PMID- 15998805
TI  - Constructing transcriptional regulatory networks.
AB  - Biological networks are the representation of multiple interactions within a
      cell, a global view intended to help understand how relationships between
      molecules dictate cellular behavior. Recent advances in molecular and
      computational biology have made possible the study of intricate transcriptional
      regulatory networks that describe gene expression as a function of regulatory
      inputs specified by interactions between proteins and DNA. Here we review the
      properties of transcriptional regulatory networks and the rapidly evolving
      approaches that will enable the elucidation of their structure and dynamic
      behavior. Several recent studies illustrate how complementary approaches combine
      chromatin immunoprecipitation (ChIP)-on-chip, gene expression profiling, and
      computational methods to construct blueprints for the initiation and maintenance
      of complex cellular processes, including cell cycle progression, growth arrest,
      and differentiation. These approaches should allow us to elucidate complete
      transcriptional regulatory codes for yeast as well as mammalian cells.

PMID- 15998806
TI  - Recruitment of the human TREX complex to mRNA during splicing.
AB  - In yeast, the TREX complex contains the THO transcription elongation complex,
      which functions in direct cotranscriptional recruitment of the mRNA export
      proteins Sub2 and Yra1 to nascent transcripts. Here we report the identification
      of the human THO complex and show that it associates with spliced mRNA, but not
      with unspliced pre-mRNA in vitro. Transcription is not required for this
      recruitment. We also show that the human THO complex colocalizes with splicing
      factors in nuclear speckle domains in vivo. Considering that splicing occurs
      cotranscriptionally in humans, our data indicate that recruitment of the human
      TREX complex to spliced mRNA is not directly coupled to transcription, but is
      instead coupled to transcription indirectly through splicing.

PMID- 15998807
TI  - The AIP2 E3 ligase acts as a novel negative regulator of ABA signaling by
      promoting ABI3 degradation.
AB  - The phytohormone abscisic acid (ABA) mediates many complex aspects of plant
      development including seed maturation, dormancy, and germination as well as root
      growth. The B3-domain transcription factor abscisic acid-insensitive 3 (ABI3) is
      a central regulator in ABA signaling, but little is known of how this factor is
      regulated. Here, we show that ABI3 is an unstable protein and that an ABI3
      interacting protein (AIP2), which contains a RING motif, can polyubiquitinate
      ABI3 in vitro. The AIP2 E3 ligase activity is abolished by mutations (C230S;
      C231S) in the RING motif and the AIP2 (C/S) mutant functions in a dominant
      negative manner. AIP2 has a stronger binding affinity for the B2 + B3 domain of
      ABI3 than the A1 + B1 domain, but only ubiquitinates the latter. In double
      transgenic plants, induced AIP2 expression leads to a decrease in ABI3 protein
      levels. In contrast, ABI3 levels are elevated upon induced expression of the AIP2
      RING mutant, which interferes with the endogenous AIP2 E3 activity. An aip2-1
      null mutant shows higher ABI3 protein levels compared with wild type after seed
      stratification, and is hypersensitive to ABA, mimicking the ABI3-overexpression
      phenotype, whereas AIP2-overexpression plants contain lower levels of ABI3
      protein than wild type and are more resistant to ABA, phenocopying abi3. Our
      results indicate that AIP2 negatively regulates ABA signaling by targeting ABI3
      for post-translational destruction.

PMID- 15998808
TI  - A systematic RNAi screen for longevity genes in C. elegans.
AB  - We report here the first genome-wide functional genomic screen for longevity
      genes. We systematically surveyed Caenorhabditis elegans genes using large-scale
      RNA interference (RNAi), and found that RNAi inactivation of 89 genes extend C.
      elegans lifespan. Components of the daf-2/insulin-like signaling pathway are
      recovered, as well as genes that regulate metabolism, signal transduction,
      protein turnover, and gene expression. Many of these candidate longevity genes
      are conserved across animal phylogeny. Genetic interaction analyses with the new
      longevity genes indicate that some act upstream of the daf-16/FOXO transcription
      factor or the sir2.1 protein deacetylase, and others function independently of
      daf-16/FOXO and sir2.1, and might define new pathways to regulate lifespan.

PMID- 15998809
TI  - Identification of a motif that mediates polypyrimidine tract-binding protein
      dependent internal ribosome entry.
AB  - We have identified a novel motif which consists of the sequence (CCU)(n) as part
      of a polypyrimidine-rich tract and permits internal ribosome entry. A number of
      constructs containing variations of this motif were generated and these were
      found to function as artificial internal ribosome entry segments (AIRESs) in vivo
      and in vitro in the presence of polypyrimidine tract-binding protein (PTB). The
      data show that for these sequences to function as IRESs the RNA must be present
      as a double-stranded stem and, in agreement with this, rather surprisingly, we
      show that PTB binds strongly to double-stranded RNA. All the cellular 5'
      untranslated regions (UTRs) tested that harbor this sequence were shown to
      contain internal ribosome entry segments that are dependent upon PTB for function
      in vivo and in vitro. This therefore raises the possibility that PTB or its
      interacting protein partners could provide a bridge between the IRES-RNA and the
      ribosome. Given the number of putative cellular IRESs that could be dependent on
      PTB for function, these data strongly suggest that PTB-1 is a universal IRES
      trans-acting factor.

PMID- 15998810
TI  - CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre
      mRNA 3'-end processing factor, Pcf11.
AB  - Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and
      transcription termination. Using elongation complexes (ECs) formed from purified
      yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from
      yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on the
      C-terminal domain (CTD) of the largest subunit of Pol II and the CTD-interaction
      domain (CID) of Pcf11. Our experiments reveal a novel termination mechanism
      whereby Pcf11 bridges the CTD to the nascent transcript and causes dissociation
      of both Pol II and the nascent transcript from the DNA in the absence of
      nucleotide hydrolysis. We posit that conformational changes in the CTD are
      transduced through Pcf11 to the nascent transcript to cause termination.

PMID- 15998811
TI  - mSin3A corepressor regulates diverse transcriptional networks governing normal
      and neoplastic growth and survival.
AB  - mSin3A is a core component of a large multiprotein corepressor complex with
      associated histone deacetylase (HDAC) enzymatic activity. Physical interactions
      of mSin3A with many sequence-specific transcription factors has linked the mSin3A
      corepressor complex to the regulation of diverse signaling pathways and
      associated biological processes. To dissect the complex nature of mSin3A's
      actions, we monitored the impact of conditional mSin3A deletion on the
      developmental, cell biological, and transcriptional levels. mSin3A was shown to
      play an essential role in early embryonic development and in the proliferation
      and survival of primary, immortalized, and transformed cells. Genetic and
      biochemical analyses established a role for mSin3A/HDAC in p53 deacetylation and
      activation, although genetic deletion of p53 was not sufficient to attenuate the
      mSin3A null cell lethal phenotype. Consistent with mSin3A's broad biological
      activities beyond regulation of the p53 pathway, time-course gene expression
      profiling following mSin3A deletion revealed deregulation of genes involved in
      cell cycle regulation, DNA replication, DNA repair, apoptosis, chromatin
      modifications, and mitochondrial metabolism. Computational analysis of the mSin3A
      transcriptome using a knowledge-based database revealed several nodal points
      through which mSin3A influences gene expression, including the Myc-Mad, E2F, and
      p53 transcriptional networks. Further validation of these nodes derived from in
      silico promoter analysis showing enrichment for Myc-Mad, E2F, and p53 cis
      regulatory elements in regulatory regions of up-regulated genes following mSin3A
      depletion. Significantly, in silico promoter analyses also revealed specific cis
      regulatory elements binding the transcriptional activator Stat and the ISWI ATP
      dependent nucleosome remodeling factor Falz, thereby expanding further the mSin3A
      network of regulatory factors. Together, these integrated genetic, biochemical,
      and computational studies demonstrate the involvement of mSin3A in the regulation
      of diverse pathways governing many aspects of normal and neoplastic growth and
      survival and provide an experimental framework for the analysis of essential
      genes with diverse biological functions.

PMID- 15998813
TI  - Unusual scars in a young female patient.

PMID- 15998812
TI  - VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart.
AB  - The strength of the heart beat can accommodate in seconds to changes in blood
      pressure or flow. The mechanism for such homeostatic adaptation is unknown. We
      sought the cause of poor contractility in the heart of the embryonic zebrafish
      with the mutation dead beat. We find through cloning that this is due to a
      mutation in the phospholipase C gamma1 (plcgamma1) gene. In mutant embryos,
      contractile function can be restored by PLCgamma1 expression directed selectively
      to cardiac myocytes. In other situations, PLCgamma1 is known to transduce the
      signal from vascular endothelial growth factor (VEGF), and we show here that
      abrogation of VEGF also interferes with cardiac contractility. Somewhat
      unexpectedly, FLT-1 is the responsible VEGF receptor. We show that the same
      system functions in the rat. Blockage of VEGF-PLCgamma1 signaling decreases
      calcium transients in rat ventricular cardiomyocytes, whereas VEGF imposes a
      positive inotropic effect on cardiomyocytes by increasing calcium transients.
      Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the
      strength of the heart beat. We speculate that this paracrine system may
      contribute to normal and pathological regulation of cardiac contractility.

PMID- 15998814
TI  - Genitourinary medicine and surgery in Nelson's navy.
AB  - Surgeons of the Royal Navy during the Napoleonic and revolutionary wars, between
      1793 and 1815, were solely responsible for all health care of the officers, men,
      and boys of their ships. This paper examines the genitourinary medicine and
      surgery encountered by the naval surgeons at the time of Nelson. Primary sources
      are examined to explore the presentation, case mix, and management of
      genitourinary disease during this period. A general overview is given of the life
      and work of the Royal Naval surgeons at the end of the 18th century. The
      documents that were examined contained 39 surgeon's journals, these were written
      by 26 surgeons on 13 different ships. The journals contained 446 presentations to
      the sick list of men with genitourinary symptoms. The presenting symptoms are
      grouped together under the following headings; venereal disease, penile
      pathology, scrotal pain and swelling, urinary symptoms and retention, stone
      disease and trauma. Examination of these journals permits a glimpse of medical
      life in the Royal Navy during the time of Nelson. The case load and management of
      genitourinary disease shows the diversity of presentation to these surgeons.

PMID- 15998815
TI  - Epidemiology of gastric cancer in Japan.
AB  - Despite its decreasing trend in Japan, gastric cancer remains an important public
      health problem. Although the age standardised rates of gastric cancer have been
      declining for decades, the absolute numbers are increasing because of the rapid
      aging of the population. A large proportion of Japanese gastric cancers are
      detected at an early stage, with a better overall survival rate. As with Western
      developed countries, a change in the social environment such as reduced salt use
      and increased fresh vegetable and fruit intake as well as improvement of food
      storage may play an important part in the decline. Differences in Helicobacter
      pylori infection rates between generations presumably have contributed to the
      generation related variation in the declining trends. It is expected that most
      gastric cancers in Japan may be preventable by lifestyle modification such as
      salt reduction and increased fruit and vegetable intake, together with avoidance
      of smoking and countermeasures against H pylori infection so that the level now
      evident in Western developed countries can be reached.

PMID- 15998816
TI  - Clinical associations of Dupuytren's disease.
AB  - Dupuytren's disease (DD) is a common progressive fibrotic condition affecting the
      palmar and digital fascia. Although its management is undertaken by hand
      surgeons, it is commonly seen by other doctors as an incidental finding. In many
      cases it is believed to be associated with other medical conditions, although the
      evidence for such associations is not always clear. This review considers the
      evidence behind these associations and discusses the aetiology of DD. By doing
      so, it is hoped that this review will permit a better understanding of the
      relevance of DD as a clinical sign.

PMID- 15998818
TI  - It is time to test low level laser therapy in Great Britain.
AB  - Low level laser therapy (LLLT) has been used in Eastern Europe and Asia for the
      treatment of a wide range of conditions for many years. Its continued acceptance
      in these populations reflects the efficacy with which it is regarded both by
      clinicians and their patients. Although there have been a substantial number of
      reports on its clinical benefit and some practitioners have used the technique in
      North America and Australasia it has yet to be subjected to detailed assessment
      through randomised clinical trials. The purpose of this review is to stimulate
      interest in the technique and to encourage rigorous research into its potential
      value.

PMID- 15998817
TI  - Psychosocial stress and cardiovascular diseases.
AB  - Fifty five years after the first finding relating mood disturbances and
      cardiovascular diseases, there is still debate on the formation of a cogent
      conception embracing all the fragments of insight within the various aspects
      relating psychosocial stress to cardiovascular diseases. The clinical comorbidity
      is empirically evident, but there are ambiguous research results limiting the
      value of the proposed pathophysiological mechanisms. Psychosocial stress
      represents here any event that relates psychological phenomena to the social
      environment and to the associated pathophysiological changes. Stress denotes the
      external or environmental factors to which people are exposed, as well as the
      behavioural or biological reaction to it (response that some authors call
      "distress"). Cardiovascular diseases will be considered here only when being the
      consequence of chronic inflammatory disease of arteries (atherosclerosis). The
      question is: are there pathophysiological reliable mechanisms relating
      psychosocial stress to the development of cardiovascular diseases?

PMID- 15998820
TI  - Approach to the patient with epilepsy in the outpatient department.
AB  - Epilepsy is common and serious (prevalence 750 per 100 000) and has an impact
      upon employment, education, and driving. The diagnosis requires a detailed
      history including witness account. Clinicians must distinguish seizures
      particularly from syncope and psychogenic attacks. Electroencephalography and
      magnetic resonance brain scanning help to identify causes and classification of
      epilepsy, but alone rarely provide the diagnosis. Antiepileptic drug treatment is
      required long term and is potentially hazardous; patients should start treatment
      only after informed discussion with an epilepsy specialist. Patients require
      reliable written information, particularly the driving regulations, and the
      impact of seizures on employment, education, and leisure. Women must understand
      the potential drug teratogenic effects. Certain patient groups benefit from
      targeted epilepsy services, for example, learning disabled, children, teenagers,
      and elderly. People with epilepsy require long term specialist follow up.
      Although this is currently provided in mainly in secondary care (including nurse
      led clinics), improved liaison with primary care should enable improved access to
      epilepsy services. Epilepsy care should be multidisciplinary and long term,
      linking primary and secondary care, and empowering patients towards improved
      management of their condition.

PMID- 15998821
TI  - Functional abdominal pain.
AB  - Functional abdominal pain or functional abdominal pain syndrome (FAPS) is an
      uncommon functional gut disorder characterised by chronic or recurrent abdominal
      pain attributed to the gut but poorly related to gut function. It is associated
      with abnormal illness behaviour and patients show psychological morbidity that is
      often minimised or denied in an attempt to discover an organic cause for
      symptoms. Thus the conventional biomedical approach to the management of such
      patients is unhelpful and a person's symptom experience is more usefully
      investigated using a biopsychosocial evaluation, which necessarily entails a
      multidisciplinary system of healthcare provision. Currently the pathophysiology
      of the disorder is poorly understood but is most likely to involve a dysfunction
      of central pain mechanisms either in terms of attentional bias, for example,
      hypervigilance or a failure of central pain modulation/inhibition. Although
      modern neurophysiological investigation of patients is promising and may provide
      important insights into the pathophysiology of FAPS, current clinical management
      relies on an effective physician-patient relationship in which limits on clinical
      investigation are set and achievable treatment goals tailored to the patient's
      needs are pursued.

PMID- 15998822
TI  - Do junior doctors know where to insert chest drains safely?
AB  - BACKGROUND: The safe insertion of a chest drain is a skill doctors across
      specialties require. Incorrect placement can lead to significant morbidity and
      even mortality. METHODS: This audit surveyed junior doctors working in a teaching
      hospital about their specialty and level of experience with intercostal drains.
      They were then asked to mark on a photograph where they would insert a chest
      drain for a pneumothorax in a non-emergency situation. RESULTS: Of the 55 junior
      doctors surveyed, 45% were outside the safe area of chest drain insertion as
      defined by the British Thoracic Society. The most common error was a choice of
      insertion site too low (24%). CONCLUSIONS: In this audit 45% of juniors surveyed
      would have placed a chest drain outside the safe triangle recommended by the
      British Thoracic Society. The common mistake of a choice of insertion site too
      low should be discussed in postgraduate teaching programmes.

PMID- 15998823
TI  - Disease progression and adverse events in patients listed for elective
      percutaneous coronary intervention.
AB  - OBJECTIVE: To record disease progression and the timing of adverse events in
      patients on a waiting list for elective percutaneous coronary intervention (PCI).
      DESIGN: Observational prospective study. SETTINGS: A UK tertiary cardiothoracic
      centre, at a time when waiting lists for PCI were up to 18 months. PATIENTS: 145
      patients (116 men, median age 59.5 years) placed on an elective waiting list for
      PCI between October 1998 and September 1999. MAIN OUTCOME MEASURES: Adverse
      events recorded were death, myocardial infarction, need for urgent hospital
      admission because of unstable angina, and need for emergency revascularisation
      while waiting for PCI. RESULTS: During a median follow up of 10 months (range 1
      18 months), nine (6.2%) patients experienced an adverse event. Eight (5.52%)
      patients were admitted with unstable angina as emergencies. One was admitted with
      a myocardial infarction. Twenty nine (20.0%) patients had significant disease
      progression at the time of the repeat angiogram before PCI. In 10 (7%), disease
      had progressed so that PCI was no longer feasible and patients were referred for
      coronary artery bypass graft. Sixteen (11%) were removed from the PCI waiting
      list because of almost complete resolution of their anginal symptoms. CONCLUSION:
      Adverse coronary events and clinically significant disease progression occur
      commonly in patients waiting for PCI. Despite the presence of severe coronary
      lesions, myocardial infarction was rare and no patients died while on the waiting
      list. Resolution of anginal symptoms was also comparatively common. The
      pathophysiology of disease progression frequently necessitates a change in the
      treatment of patients waiting for PCI.

PMID- 15998824
TI  - Sexually inappropriate behaviour in demented elderly people.
AB  - AIM: To determine the prevalence, aetiology, and treatment profile of abnormal
      sexual behaviour in subjects with dementia in psychogeriatric practices. METHODS:
      A retrospective cross sectional study was conducted in a long term care
      psychiatry consultation service, community based geriatric psychiatry service,
      and an inpatient dementia behavioural unit in Edmonton, Canada. RESULTS: Forty
      one subjects (1.8%) had sexually inappropriate behaviour. Of those cognitively
      impaired subjects with sexually inappropriate behaviour, 20 (48.8%) were living
      in nursing homes and the rest, 21 (51.2%) in the community. Of these subjects,
      53.7% had vascular dementia, 22% had Alzheimer's, and 9.8% had mild cognitive
      impairment. History of alcohol misuse and psychosis were reported in 14.6% and
      9.8% of subjects respectively. Twenty seven (65.7%) had verbally inappropriate
      behaviour and 36 (87.8%) had physically inappropriate behaviour. In this study,
      verbally inappropriate behaviour was more commonly seen in the community sample
      (81%) than in the nursing home sample (50%) (p = 0.04). Behavioural treatment was
      also more commonly seen in the community sample (81%) than in the nursing home
      sample (45%) (p = 0.01). CONCLUSION: In this study sexually inappropriate
      behaviour was seen in all stages of dementia, more commonly associated with
      subjects of vascular aetiology, and is as commonly seen in community dwelling
      subjects with dementia as in nursing home subjects.

PMID- 15998825
TI  - Measuring the quality of referral letters about patients with upper
      gastrointestinal symptoms.
AB  - BACKGROUND: General practitioners state the reason for referring patients in
      referral letters. The paucity of information in these letters has been the source
      of criticism from specialist colleagues. OBJECTIVE: To invite general
      practitioners to set standards for referral letters to gastroenterologists and to
      apply these standards to actual referral letters to one specialist
      gastroenterology unit. METHODS: A scoring schedule was designed based on the
      responses to a questionnaire survey of a large sample of all general
      practitioners in one locality. Altogether 350 consecutive letters to a district
      general hospital about patients referred for an upper gastrointestinal specialist
      opinion were subsequently scored using the schedule. RESULTS: 102 practitioners
      responded to the survey. Their responses imply that colleagues assess and record
      findings on 18 potential features of upper bowel disease. In practice most
      referral letters address fewer than six features of upper bowel disease. The mean
      number of positive features of upper gastrointestinal disease reported in each
      letter was one. CONCLUSIONS: This study reported a failure to meet "peer defined"
      standards for the content of referral letters set by colleagues in one locality.
      Referral letters serve many purposes, however, encouraging full documentation of
      specific clinical findings may serve to increase the pre-referral assessments
      performed in practice.

PMID- 15998827
TI  - Co-morbidity in general practice.
AB  - BACKGROUND: Co-morbidity, or the presence of more than one clinical condition, is
      gaining increased attention in epidemiological and health services research.
      However, the clinical relevance of co-morbidity has yet to be defined. In general
      practice, few studies have been conducted into co-morbidity, either at a single
      health care encounter, an episode of care, or for a defined time period. AIMS: To
      describe the major co-morbidity cluster profiles recorded by general
      practitioners. Another aim of this study is to describe the common clusters of co
      prescribing. METHODS AND RESULTS: Twelve month data from patients attending 156
      GPs from 95 practices around a six month period of January to June 2003 were
      analysed. This represented 840,961 encounters from about 200,000 individual
      patients at these participating practices. Co-morbidity and co-prescribing
      cluster profiles are represented by problems managed and reasons for prescribing
      for the top 10 presentations and top 10 prescribed drugs in the study period.
      CONCLUSIONS: By analysing the 10 most prevalent problems and 10 most prevalent
      drugs prescribed in consultations in a community sample, other co-morbidities
      that are particular to general practice, for example hypertension and lipid
      disorders, can be uncovered. Whether these clusters are causally related or occur
      by chance requires further analysis.

PMID- 15998826
TI  - Aneurysmal subarachnoid haemorrhage: guidance in making the correct diagnosis.
AB  - BACKGROUND: The natural history of untreated aneurysmal subarachnoid haemorrhage
      carries a dismal prognosis. Case fatalities range between 32% and 67%. Treatment
      with either surgical clipping or endovascular coiling is highly successful at
      preventing re-bleeding and yet the diagnosis is still missed. METHODS: Based on
      the national guidelines for analysis of cerebrospinal fluid for bilirubin in
      suspected subarachnoid haemorrhage and a review of other available literature
      this study has compiled guidance in making the diagnosis. CONCLUSION: In patients
      presenting with a suspected non-traumatic subarachnoid haemorrhage, computed
      tomography within 12 hours will reliably show 98% of subarachnoid haemorrhage. In
      patients who present after 12 hours with a negative computed tomogram, formal
      cerebrospinal fluid spectophotometry will detect subarachnoid haemorrhage for the
      next two weeks with a reliability of 96%. Between the early diagnosis with the
      aid of computed tomography and the later diagnosis with the added benefit of
      spectophotometry in the period where computed tomograms become less reliable, it
      should be possible to diagnose most cases of subarachnoid haemorrhage correctly.

PMID- 15998828
TI  - Handheld computers in medicine: the way forward.
AB  - Handheld computers are now a common sight in medicine, but there are scarce data
      on who actually uses them and what functions are found to be most useful. This is
      the first study of handheld computer use in a British hospital, and shows that
      there is already considerable use and acceptance of the technology, with 22 of 55
      (40%) physicians possessing and using such a device. Doctors in training grades
      are more likely to make use of medical software, particularly textbooks,
      calculators, and formularies. The main barriers to greater use of this technology
      were cost of software and poor applicability to UK practice.

PMID- 15998830
TI  - Competitive regulation of hepcidin mRNA by soluble and cell-associated
      hemojuvelin.
AB  - Mutations in a recently identified gene HJV (also called HFE2, or repulsive
      guidance molecule C, RgmC) are the major cause of juvenile hemochromatosis (JH).
      The protein product of HJV, hemojuvelin, contains a C-terminal
      glycosylphosphatidylinositol anchor, suggesting that it can be present in either
      a soluble or a cell-associated form. Patients with HJV hemochromatosis have low
      urinary levels of hepcidin, the principal iron-regulatory hormone secreted by the
      liver. However, neither the specific role of hemojuvelin in maintaining iron
      homeostasis nor its relationship to hepcidin has been experimentally established.
      In this study we used hemojuvelin-specific siRNAs to vary hemojuvelin mRNA
      concentration and showed that cellular hemojuvelin positively regulated hepcidin
      mRNA expression, independently of the interleukin 6 pathway. We also showed that
      recombinant soluble hemojuvelin (rs-hemojuvelin) suppressed hepcidin mRNA
      expression in primary human hepatocytes in a log-linear dose-dependent manner,
      suggesting binding competition between soluble and cell-associated hemojuvelin.
      Soluble hemojuvelin was found in human sera at concentrations similar to those
      required to suppress hepcidin mRNA in vitro. In cells engineered to express
      hemojuvelin, soluble hemojuvelin release was progressively inhibited by
      increasing iron concentrations. We propose that soluble and cell-associated
      hemojuvelin reciprocally regulate hepcidin expression in response to changes in
      extracellular iron concentration.

PMID- 15998829
TI  - Polymerization of fibrin: specificity, strength, and stability of knob-hole
      interactions studied at the single-molecule level.
AB  - Using laser tweezers, we measured for the first time the forces of individual
      knob-into-hole interactions underlying fibrin polymerization. Exposure of A-knobs
      in desA-fibrin or its fragment from the central part of the molecule (N-terminal
      disulphide knot, NDSK) resulted in strong interactions with fibrinogen or
      fragment D (containing only a- and b-holes), producing a binding strength of
      approximately 125 to 130 pN. The interactions were not present in the absence of
      either knobs or holes and were abrogated by a specific inhibitor of fibrin
      polymerization, a peptide mimic of the A-knob (GPRPam). Exposure of both the A-
      and B-knobs in desAB-fibrin or desAB-NDSK did not change the rupture force
      spectra compared with the desA molecules, and their interactions with fibrinogen
      remained highly sensitive to GPRPam but not to GHRPam (B-knob), suggesting that
      neither A:b nor B:b nor B:a contacts contributed significantly to binding
      strength in addition to A:a contacts. The A:a interactions had a relatively small
      zero-force off-rate of approximately 10(-4) s(-1) and tight knob-to-hole contacts
      characterized by a transition state distance of approximately 0.3 nm. The results
      demonstrate that the knob-hole binding during thrombin-induced fibrin
      polymerization is driven by strong, stable, and highly specific A:a bonding,
      whereas A:b, B:b, or B:a interactions were not detected.

PMID- 15998831
TI  - Quiescent and activated mouse granulocytes do not express granzyme A and B or
      perforin: similarities or differences with human polymorphonuclear leukocytes?
AB  - Polymorphonuclear leukocytes have been shown to use a multitude of effector
      functions to combat pathogens and tumors, including enzymes, defensins, and toxic
      products such as oxygen radicals and nitrogen oxides. Recent studies provided
      evidence for the expression of granzymes (gzms) and perforin (perf) within the
      cytotoxic arsenal of human neutrophils, the validity of which was questioned by 2
      subsequent studies. We have now used cytology, intracellular flow cytometry,
      enzymatic assays, immunoelectron microscopy, and quantitative reverse
      transcriptase-polymerase chain reaction to obtain evidence of the presence of
      gzms and/or perf in mouse Gr-1+ granulocyte populations. The data obtained
      clearly demonstrate that neither in vitro- nor in vivo-derived mouse granulocytes
      synthesize gzmA and gzmB or perf, even following infection/immunization with
      pathogens or pathogen-derived material. A parallel comparable analysis on the
      expression of gzmB in human neutrophils from 3 healthy control subjects and 4
      patients with diverse diseases failed to detect gzmB expression. The data
      indicate that polymorphonuclear leukocytes from mice and humans lack the 3
      cytotoxic effector molecules, gzmA, gzmB, and perf, generally associated with
      natural killer and cytotoxic T lymphocytes.

PMID- 15998833
TI  - Improved outcome in central nervous system aspergillosis, using voriconazole
      treatment.
AB  - The mortality of central nervous system (CNS) aspergillosis approaches 100%,
      requiring improved therapies. Voriconazole gives superior efficacy and survival
      in invasive aspergillosis, compared with amphotericin B. Also, in contrast to
      other antifungal drugs, voriconazole penetrates well into the CNS. We evaluated,
      retrospectively, the outcome and survival of 81 patients who were treated with
      voriconazole for definite (n = 48) or probable (n = 33) CNS aspergillosis.
      Complete and partial responses were recorded in 35% of patients and varied by the
      underlying disease group: hematologic malignancies (54%), other underlying
      conditions (50%), chronic immunosuppression (45%), solid organ transplantation
      (36%), and hematopoietic stem cell transplantation (16%). Thirty-one percent of
      patients survived CNS aspergillosis for a median observation time of 390 days.
      There were 31 patients who underwent neurosurgical procedures, including
      craniotomy/abscess resection (n = 14), abscess drainage (n = 12), ventricular
      shunt (n = 4), and Ommaya-reservoir (n = 1). Multifactorial analysis revealed
      that neurosurgery was associated with improved survival (P = .02). Patients who
      underwent hematopoietic stem cell transplantation had a poorer survival (P =
      .02), but 7 (22%) of 32 survived for a median of 203 days. We conclude from this
      large cohort of patients that voriconazole treatment together with neurosurgical
      management, whenever feasible, is currently the best approach to treat patients
      with CNS aspergillosis.

PMID- 15998832
TI  - Optimal biologic dose of metronomic chemotherapy regimens is associated with
      maximum antiangiogenic activity.
AB  - Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment
      strategy thought to have an antiangiogenic basis. However, the advantages of
      reduced toxicity, increased efficacy in some cases, and ability to combine
      chemotherapy administered long term in this way with targeted therapies can be
      compromised by the empiricism associated with determining the optimum biologic
      dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different
      preclinical tumor models, including a hematologic malignancy, we established the
      OBD by determining the maximum efficacy associated with minimum or no toxicity.
      We then found each OBD to be strikingly correlated with the maximum reduction in
      viable peripheral blood circulating vascular endothelial growth factor receptor 2
      positive (VEGFR-2+) endothelial precursors (CEPs). These results suggest that
      CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic
      chemotherapy regimens.

PMID- 15998834
TI  - An alternative exon 1 of the CD5 gene regulates CD5 expression in human B
      lymphocytes.
AB  - T lymphocytes and a subpopulation of B lymphocytes express the CD5 coreceptor.
      Its functional importance is evident from the multiple levels and developmental
      stages of the regulation of its expression. We here report the discovery of a
      novel regulatory exon upstream of the noncoding region of the CD5 gene in humans.
      This alternate exon 1 is designated E1B (with the conventional exon 1 renamed
      E1A) and was shown to regulate the expression of CD5. E1B-containing transcripts
      existed exclusively in B lymphocytes and encoded a protein that was truncated and
      retained intracellularly. As a consequence, the amount of E1A-containing
      transcripts was down-regulated and the membrane CD5 expression was diminished in
      the presence of E1B-containing transcripts. High levels of E1A transcripts were
      found in chronic lymphocytic leukemia, and there were no E1A transcripts in 697
      pre-B cells, which have no membrane CD5. Introduction of E1B into Jurkat cells
      reduced their membrane expression of CD5, and sequence analysis revealed that the
      E1B motif is a defective human endogenous retrovirus. A balance between the 2
      alternative exons 1 might be central to the regulation of membrane CD5 in human B
      cells, and, through CD5-associated SH2-containing phosphatase 1, to the
      modulation of B-cell antigen receptor-transduced signals.

PMID- 15998835
TI  - RGS16 is a negative regulator of SDF-1-CXCR4 signaling in megakaryocytes.
AB  - Regulators of G-protein signaling (RGS) constitute a family of proteins involved
      in the negative regulation of signaling through heterotrimeric G protein-coupled
      receptors (GPCRs). Several RGS proteins have been implicated in the down
      regulation of chemokine signaling in hematopoietic cells. The chemokine stromal
      cell-derived factor 1 (SDF-1) activates migration of hematopoietic progenitors
      cells but fails to activate mature megakaryocytes despite high levels of CXC
      chemokine receptor 4 (CXCR4) receptor expression in these cells. This prompted us
      to analyze RGS expression and function during megakaryocyte differentiation. We
      found that RGS16 and RGS18 mRNA expression was up-regulated during this process.
      Overexpressing RGS16 mRNA in the megakaryocytic MO7e cell line inhibited SDF-1
      induced migration, mitogen-activated protein kinase (MAPK) and protein kinase B
      (AKT) activation, whereas RGS18 overexpression had no effect on CXCR4 signaling.
      Knocking down RGS16 mRNA via lentiviral-mediated RNA interference increased CXCR4
      signaling in MO7e cells and in primary megakaryocytes. Thus, our data reveal that
      RGS16 is a negative regulator of CXCR4 signaling in megakaryocytes. We postulate
      that RGS16 regulation is a mechanism that controls megakaryocyte maturation by
      regulating signals from the microenvironment.

PMID- 15998836
TI  - Gefitinib induces myeloid differentiation of acute myeloid leukemia.
AB  - Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever
      increasing dose intensity of cytotoxic therapy. In an effort to identify novel
      approaches to AML therapy, we recently reported a new method of chemical
      screening based on the modulation of a gene expression signature of interest. We
      applied this approach to the discovery of AML-differentiation-promoting
      compounds. Among the compounds inducing neutrophilic differentiation was DAPH1
      (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth
      factor receptor (EGFR) kinase activity. Here we report that the Food and Drug
      Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the
      differentiation of AML cell lines and primary patient-derived AML blasts in
      vitro. Gefitinib induced differentiation based on morphologic assessment, nitro
      blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene
      expression, and inhibition of proliferation at clinically achievable doses.
      Importantly, EGFR expression was not detected in AML cells, indicating that
      gefitinib functions through a previously unrecognized EGFR-independent mechanism.
      These studies indicate that clinical trials testing the efficacy of gefitinib in
      patients with AML are warranted.

PMID- 15998837
TI  - Humanized anti-interleukin-6 receptor antibody treatment of multicentric
      Castleman disease.
AB  - Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder
      characterized by systemic lymphadenopathy and constitutional inflammatory
      symptoms. Dysregulated overproduction of interleukin-6 is responsible for the
      clinical abnormalities. This multicenter prospective study was undertaken to
      evaluate the safety and efficacy of a humanized anti-human interleukin-6 (IL-6)
      receptor monoclonal antibody (MRA) in patients with MCD. We report here results
      of the first 60 weeks of the study enrolling 28 patients. The initial dosing
      period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments
      in the dose and treatment interval were allowed for each patient in an extension
      phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated
      lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and
      total cholesterol levels, high-density lipoprotein cholesterol values, and body
      mass index all increased significantly. In addition, fatigue diminished. Chronic
      inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%)
      patients, the MRA dose was decreased or the treatment interval was extended
      without exacerbation. Eleven (73.3%) of 15 patients who had received oral
      corticosteroids before study entry were able to do well on a reduced
      corticosteroid dose. Most adverse events were mild to moderate in severity. MRA
      was tolerated well and significantly alleviated chronic inflammatory symptoms and
      wasting in patients with MCD.

PMID- 15998838
TI  - Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an
      analysis of prognostic factors from the Chronic Leukemia Working Party of the
      EBMT.
AB  - This study reports outcomes of allogeneic hematopoietic stem cell transplantation
      with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid
      leukemia (CML) from the European Group for Blood and Marrow Transplantation
      (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1),
      CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant
      score was 3. The day 100 transplantation-related mortality (TRM) was 6.1%
      (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years.
      Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with
      the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease
      (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%).
      ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall
      survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%
      66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced
      disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7)
      and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are
      feasible in CML in first or second CP. Since no other RIC regimen demonstrated
      superiority, Fd/Bu/ATG should be considered as baseline in future prospective
      trials.

PMID- 15998840
TI  - Mesangial cell-reduced Ca2+ signaling in high glucose is due to inactivation of
      phospholipase C-beta3 by protein kinase C.
AB  - In high glucose, glomerular mesangial cells (MCs) demonstrate impaired Ca(2+)
      signaling in response to seven-transmembrane receptor stimulation. To identify
      the mechanism, we first postulated decreased release from intracellular stores.
      Intracellular Ca(2+) was measured in fluo-3-loaded primary cultured rat MCs using
      confocal fluorescence microscopy. In high glucose (HG) 30 mM for 48 h, the 25 nM
      ionomycin-stimulated intracellular Ca(2+) response was reduced to 82% of that
      observed in normal glucose (NG). In NG 5.6 mM, Ca(2+) responses to endothelin
      (ET)-1 and platelet-derived growth factor (PDGF) were unchanged in cells cultured
      in 50 nM Ca(2+) vs. 1.8 mM Ca(2+). Depletion of intracellular Ca(2+) stores with
      thapsigargin eliminated ET-1-stimulated Ca(2+) responses. Incubation in 30 mM
      glucose (HG) for 48 h or stimulation with phorbol myristate acetate (PMA) for 10
      min eliminated the Ca(2+) response to ET-1 but had no effect on the PDGF
      response. Downregulation of protein kinase C (PKC) with 24-h PMA or inhibition
      with Go6976 in HG normalized the Ca(2+) response to ET-1. Because ET-1 and PDGF
      stimulate Ca(2+) signaling through different phospholipase C pathways, we
      hypothesized that, in HG, PKC selectively phosphorylates and inhibits PLC
      beta(3). Using confocal immunofluorescence imaging, in NG, a 1.6- to 1.7-fold
      increase in PLC-beta(3) Ser(1105) phosphorylation was observed following PMA or
      ET-1 stimulation for 10 min. In HG, immunofluorescent imaging and immunoblotting
      showed increased PLC-beta(3) phosphorylation, without change in total PLC
      beta(3), which was reversed with 24-h PMA or Go6976. We conclude that reduced
      Ca(2+) signaling in HG cannot be explained by reduced Ca(2+) stores but is due to
      conventional PKC-dependent phosphorylation and inactivation of PLC-beta(3).

PMID- 15998839
TI  - Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin
      D metabolism.
AB  - FGF23 suppresses both serum phosphate and 1,25-dihydroxyvitamin D [1,25D] levels
      in vivo. Because 1,25D itself is a potent regulator of phosphate metabolism, it
      has remained unclear whether FGF23-induced changes in phosphate metabolism were
      caused by a 1,25D-independent mechanism. To address this issue, we intravenously
      administered recombinant FGF23 to vitamin D receptor (VDR) null (KO) mice as a
      rapid bolus injection and evaluated the early effects of FGF23. Administration of
      recombinant FGF23 further decreased the serum phosphate level in VDR KO mice,
      accompanied by a reduction in renal sodium-phosphate cotransporter type IIa
      (NaPi2a) protein abundance and a reduced renal 25-hydroxyvitamin D-1alpha
      hydroxylase (1alphaOHase) mRNA level. Thus FGF23-induced changes in NaPi2a and
      1alphaOHase expression are independent of the 1,25D/VDR system. However, 24
      hydroxylase (24OHase) mRNA expression remained undetectable by the treatment with
      FGF23. We also analyzed the regulatory mechanism for FGF23 expression. The serum
      FGF23 level was almost undetectable in VDR KO mice, whereas dietary calcium
      supplementation significantly increased circulatory levels of FGF23 and its mRNA
      abundance in bone. This finding indicates that calcium is another determinant of
      FGF23 production that occurs independently of the VDR-mediated mechanism. In
      contrast, dietary phosphate supplementation failed to induce FGF23 expression in
      the absence of VDR, whereas marked elevation in circulatory FGF23 was observed in
      wild-type mice fed with a high-phosphate diet. Taken together, FGF23 works, at
      least in part, in a VDR-independent manner, and FGF23 production is also
      regulated by multiple mechanisms involving VDR-independent pathways.

PMID- 15998841
TI  - A critical role for enhanced TGF-alpha and EGFR expression in the initiation of
      parathyroid hyperplasia in experimental kidney disease.
AB  - The parathyroid hyperplasia secondary to kidney disease is associated with
      enhanced expression of the growth promoter transforming growth factor-alpha (TGF
      alpha). TGF-alpha stimulates growth through activation of its receptor, the
      epidermal growth factor receptor (EGFR), normally expressed in the parathyroid
      glands. Because enhanced coexpression of TGF-alpha and EGFR causes aggressive
      cellular growth, these studies utilized highly specific inhibitors of EGFR
      tyrosine kinase, a step mandatory for TGF-alpha-induced EGFR activation, to
      assess the contribution of growth signals from enhanced expression of TGF-alpha
      exclusively or both TGF-alpha and EGFR to the rapid parathyroid growth induced by
      kidney disease and exacerbated by high-phosphorus (P) and low-calcium (Ca) diets
      in rats. The enhancement in parathyroid gland weight and proliferating activity
      (proliferating cell nuclear antigen/Ki67) induced by kidney disease and
      aggravated by either high P or low Ca intake, within the first week after 5/6
      nephrectomy, in rats, coincided with simultaneous increases (2- to 3-fold) in TGF
      alpha and EGFR content. Conversely, prevention of the increases in both TGF-alpha
      and EGFR paralleled the efficacy of either P restriction or high-Ca intake in
      ameliorating uremia-induced parathyroid hyperplasia. More importantly,
      suppression of TGF-alpha/EGFR signaling, through prophylactic administration of
      potent and highly selective inhibitors of ligand-induced EGFR activation,
      completely prevented both high-P- and low-Ca-induced parathyroid hyperplasia as
      well as TGF-alpha self-upregulation. Thus enhanced parathyroid TGF-alpha/EGFR
      expression, self-upregulation, and growth signals occur early in kidney disease,
      are aggravated by low-Ca and high-P intake, and constitute the main pathogenic
      mechanism of the severity of parathyroid hyperplasia.

PMID- 15998842
TI  - Renocortical mRNA expression of vasoactive factors during spironolactone
      protective effect in chronic cyclosporine nephrotoxicity.
AB  - We showed that spironolactone reduced structural damage and prevented renal
      dysfunction in chronic cyclosporine (CsA) nephrotoxicity. These findings
      evidenced an aldosterone renal vascular effect under this condition. To
      investigate aldosterone's role in modulating renal vascular tone, renocortical
      vasoactive pathways mRNA levels in chronic CsA nephrotoxicity as well as
      spironolactone's effect on renal function in acute CsA nephrotoxicity were
      evaluated. Two experimental sets were designed. For chronic nephrotoxicity, rats
      fed with low-sodium diet were divided into groups receiving vehicle,
      spironolactone (Sp), CsA, and CsA+Sp, for 21 days. Creatinine clearance, survival
      percentage, and renocortical mRNA levels of pro-renin, angiotensinogen (Ang),
      angiotensin receptors (AT(1A), AT(1B), and AT(2)), preproendothelin, endothelin
      receptors (ET(A), ET(B)), cyclooxygenase-2 (COX-2), and adenosine receptors
      (Ad(1), Ad(2A), Ad(2B), and Ad(3)) were analyzed. For acute nephrotoxicity,
      similar groups fed with a standard chow diet for 7 days were included. Serum
      potassium and sodium, glomerular filtration rate (GFR), and renal blood flow
      (RBF) were determined. In chronic model, CsA produced pro-renin and ET
      upregulation, altered adenosine receptors expression, and reduced Ang, AT(1A),
      AT(1B), ET(B), and COX-2 mRNA levels. Spironolactone protective effect in chronic
      nephrotoxicity was associated with prevention of pro-renin upregulation and
      increased AT(2), together with ET(B) reduction. In acute nephrotoxicity,
      spironolactone completely prevented GFR and RBF reduction induced by CsA. Our
      results suggest that aldosterone contributes to renal vasoconstriction observed
      in CsA nephrotoxicity and that renoprotection conferred by spironolactone was
      related to modification of renocortical vasoactive pathways expression, in which
      pro-renin normalization was the most evident change in chronic nephropathy.
      Finally, our data point to spironolactone as a potential treatment to reduce CsA
      nephrotoxicity in transplant patients.

PMID- 15998844
TI  - Defective water and glycerol transport in the proximal tubules of AQP7 knockout
      mice.
AB  - The aquaporin-7 (AQP7) water channel is known as a member of the
      aquaglyceroporins, which facilitate the transport of glycerol as well as water.
      Although AQP7 is abundantly expressed on the apical membrane of the proximal
      straight tubules in the kidney, the physiological role of AQP7 is still unknown.
      To investigate this, we generated AQP7 knockout mice. The water permeability of
      the proximal tubule brush-border membrane measured by the stopped-flow method was
      slightly but significantly reduced in the AQP7 knockout mice compared with that
      of wild-type mice (AQP7, 18.0 +/- 0.4 x 10(-3) cm/s vs. wild-type, 20.0 +/- 0.3 x
      10(-3) cm/s). Although AQP7 solo-knockout mice did not exhibit a urinary
      concentrating defect, AQP1/AQP7 double-knockout mice had a reduction in urinary
      concentrating ability compared with AQP1 solo-knockout mice, suggesting that the
      amount of water reabsorbed through AQP7 in the proximal straight tubules is
      physiologically substantial. On the other hand, AQP7 knockout mice showed marked
      glyceroluria (AQP7, 1.7 +/- 0.34 mg/ml vs. wild-type, 0.005 +/- 0.002 mg/ml).
      This identified a novel glycerol reabsorption pathway in the proximal straight
      tubules. In two mouse models of proximal straight tubule injury, the cisplatin
      induced acute renal failure (ARF) model and the ischemic ARF model, an increase
      in urine glycerol was observed (pretreatment, 0.007 +/- 0.005 mg/ml; cisplatin,
      0.063 +/- 0.043 mg/ml; ischemia, 0.076 +/- 0.02 mg/ml), suggesting that urine
      glycerol could be used as a new biomarker for detecting proximal straight tubule
      injury.

PMID- 15998843
TI  - Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced by L
      NAME treatment in pregnant rats.
AB  - We previously reported that inhibition of nitric oxide (NO) synthesis by N-nitro
      L-arginine methyl ester (L-NAME) during late pregnancy leads to increased
      production of renal vascular 20-hydroxyeicosatetraenoic acid (20-HETE), a
      cytochrome P-450 (CYP) 4A-derived vasoconstrictor, in pregnant rats. However, the
      effect of upregulation of vascular 20-HETE production on renal function after NO
      inhibition is not known. To test the hypothesis that increased gestational
      vascular 20-HETE synthesis after NO inhibition is involved in mediating blood
      pressure and renal functional changes, we first determined the IC(50) value of
      the effect of nitroprusside (SNP), a NO donor, on renal 20-HETE production in
      cortical microsomes. We then divided pregnant rats and age-matched virgin rats
      into a vehicle control group, an L-NAME treatment group (0.25 mg/ml in drinking
      water), and a group treated with L-NAME plus N-methylsulfonyl-12,12-dibromododec
      11-enamide (DDMS; CYP4A-selective inhibitor, 10 mg.kg(-1).day(-1) iv). After 4
      days of treatment, we measured blood pressure, renal blood flow (RBF), renal
      vascular resistance (RVR), and glomerular filtration rate (GFR) in each group.
      The addition of SNP (IC(50) = 22 microM) decreased renal cortical 20-HETE
      production. In pregnant rats, L-NAME treatment led to significantly higher mean
      arterial pressure (MAP) and RVR, and lower RBF and GFR. Combined treatment with
      DDMS and L-NAME significantly attenuated the increases in MAP and RVR and the
      decrease in GFR, but not the reduction in RBF induced by L-NAME treatment. L-NAME
      and L-NAME plus DDMS had no significant impact on renal hemodynamics in virgin
      rats. In addition, chronic treatment with DDMS selectively inhibited cortical 20
      HETE production without a significant effect on CYP4A expression in L-NAME
      treated pregnant rats. In conclusion, NO effectively inhibits renal cortical
      microsomal 20-HETE production in female rats. In pregnant rats, the augmentation
      of renal 20-HETE production after NO inhibition is associated with increased MAP
      and RVR, whereas decreased GFR is negated by treatment of a selective and
      competitive CYP4A inhibitor. These results demonstrate that the interaction
      between renal 20-HETE and NO is important in the regulation of renal function and
      blood pressure in pregnant rats.

PMID- 15998845
TI  - Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal
      failure: role of nitric oxide and caspases.
AB  - Acute renal failure (ARF) is a frequent and serious complication of endotoxemia
      caused by lipopolysaccharide (LPS) and contributes significantly to mortality.
      The present studies were undertaken to examine the roles of nitric oxide (NO) and
      caspase activation on renal peritubular blood flow and apoptosis in a murine
      model of LPS-induced ARF. Male C57BL/6 mice treated with LPS (Escherichia coli)
      at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a
      significant decrease in peritubular capillary perfusion. Vessels with no flow
      increased from 7 +/- 3% in the saline group to 30 +/- 4% in the LPS group (P <
      0.01). Both the inducible NO synthase inhibitor L-N(6)-1-iminoethyl-lysine (L
      NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion
      deficits. Renal failure was also associated with an increase in renal caspase-3
      activity and an increase in renal apoptosis. Both L-NIL and Z-VAD prevented these
      changes. LPS caused an increase in NO production that was blocked by L-NIL but
      not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal
      caspases and the resulting disruption in peritubular blood flow are an important
      mechanism of LPS-induced ARF.

PMID- 15998846
TI  - Disruption of glomerular cell-cell and cell-matrix interactions in hydrocarbon
      nephropathy.
AB  - Environmental chemicals play an etiological role in greater than 50% of
      idiopathic glomerular diseases. The present studies were conducted to define
      mechanisms of renal cell-specific hydrocarbon injury. Female rats were given 10
      mg/kg benzo(a)pyrene (BaP) once a week for 16 wk. Progressive elevations in total
      urinary protein, protein/creatinine ratios, and microalbuminuria were observed in
      rats treated with BaP for up to 16 wk. The nephropathic response involved early
      reductions in mesangial cell numbers and fibronectin levels by 8 wk, coupled to
      transient increases in podocyte cellularity. Changes in podocyte numbers subsided
      by 16 wk and correlated with rebound increases in mesangial cell numbers and
      fibronectin levels, along with increased alpha-smooth muscle actin and Cu/Zn
      superoxide dismutase and fusion of podocyte foot processes. In culture, mesangial
      cells were more sensitive than podocytes to hydrocarbon injury and expressed
      higher levels of inducible aryl hydrocarbon hydroxylase activity. Naive mesangial
      cells exerted a strong inhibitory influence on podocyte proliferation under both
      direct and indirect coculture conditions, and this response involved a mesangial
      cell-derived matrix that selectively inhibited podocyte proliferation. These
      findings indicate that hydrocarbon nephropathy in rats involves disruption of
      glomerular cell-cell and cell-matrix interactions mediated by deposition of a
      mesangial cell-derived growth-inhibitory matrix that regulates podocyte
      proliferation.

PMID- 15998847
TI  - Agricultural dust production in standard and conservation tillage systems in the
      San Joaquin Valley.
AB  - The negative health effects of repeated dust exposure have been well documented.
      In California's San Joaquin Valley, agricultural operations may contribute
      substantially to airborne particulates. We evaluated four management systems to
      assess impacts on dust production and soil properties for a cotton (Gossypium
      hirsutum L.)-tomato (Lycopersicon esculentum Mill.) rotation: standard tillage
      with (STCC) and without (STNO) cover crop, and conservation tillage with (CTCC)
      and without (CTNO) cover crop. Gravimetric analysis of total dust (TD, <100-mum
      aerodynamic diameter) and respirable dust (RD, 4-mum aerodynamic diameter)
      samples collected in the plume generated by field implements showed that dust
      concentrations for CTNO treatments were about one-third of their STNO
      counterparts for both cumulative TD and RD measured throughout the two-year
      rotation, primarily due to fewer in-field operations. The TD and RD production
      for STNO and STCC was comparable, whereas the CTCC system produced about twice as
      much TD and RD as CTNO. Energy dispersive spectroscopy (EDS) analyses showed
      absolute increases of 8 and 39% organic fragments in STCC and CTCC over STNO and
      CTNO, respectively, while organic fragments in the TD increased by 6% in both
      cover crop treatments. Soil C content was positively correlated with clay content
      and increased by an average of 0.12 and 0.07% in the cover crop and non-cover
      crop treatments, respectively, although soil C for each treatment showed a
      distinct response to a field texture gradient. While dust emissions show an
      immediate decrease due to fewer field operations for the conservation tillage
      treatments, long-term sampling is necessary to determine the effects that
      increased aggregation through organic matter additions may have on dust
      production.

PMID- 15998848
TI  - Maximum rates of nitrate removal in a denitrification wall.
AB  - Denitrification walls are constructed by mixing a carbon source such as sawdust
      into soils through which ground water passes. These systems can reduce nitrate
      inputs to receiving waters by enhancing denitrification. Maximum rates of nitrate
      removal by denitrification need to be determined for design purposes. To
      determine maximum rates of nitrate removal we added excess nitrate (50 mg N L(
      1)) to a trench up-gradient of a denitrification wall during a 9-d trial. Bromide
      (100 g L(-1)) was also added as a conservative tracer. Movement of nitrate and
      bromide was measured from shallow wells and soil samples were removed for
      measurements of denitrification, carbon availability, nitrate, and other
      microbial parameters. Rates of nitrate removal, determined from the ratio of NO3
      N to Br and ground water flow, averaged 1.4 g N m(-3) of wall d(-1) and were
      markedly greater than denitrification rates determined using the acetylene block
      technique (average: 0.11 g N m(-3) of wall d(-1)). These nitrate removal rates
      were generally lower than reported in other denitrification walls.
      Denitrification rates increased when nitrate was added to the laboratory
      incubations, indicating that despite large nitrate inputs in the field,
      denitrification remained limited by nitrate. This limitation was partially
      attributed to nitrate predominantly moving through zones of greater hydraulic
      conductivity or in the mobile fraction of the ground water and slow diffusion to
      the immobile fraction where denitrifiers were active.

PMID- 15998849
TI  - Phosphorus leaching in sandy outwash soils following potato-processing wastewater
      application.
AB  - Land application of wastewater presents potential for ground water pollution if
      not properly managed. In situ breakthrough tests were conducted using potato
      (Solanum tuberosum L.)-processing wastewater and a Br tracer to characterize P
      leaching in seasonally frozen sandy outwash soils. In the first test, P and Br
      breakthrough were measured in a 7-m deep well following wastewater [2.94 mg L(-1)
      total P (TP); 280 mg L(-1) Br] application at the site that had 13.1 mg water
      extractable P (WEP) kg(-1)and 94.4 mg Bray-1 P kg(-1). Bromide was detected in
      the well after approximately 0.4 pore volumes, but there was no P break-through
      after 7 pore volumes. In the second breakthrough test, wastewater containing 3.6
      mg L(-1) TP and 259 mg L(-1) Br was applied on 1.5-m deep lysimeters at low (0.8
      mg WEP kg(-1); 12.1 mg Bray-1 P kg(-1)) and high soil test P sites (104 mg WEP
      kg(-1); 585 mg Bray-1 P kg(-1)). Leachate TP concentration during the test
      remained constant (0.04 mg L(-1)) at the low P sites but increased from
      approximately 3.5 to 5.6 mg L(-1) at the high P sites. These results indicate no
      P leaching in low P soils, but leaching in high P soils, thus suggesting that
      most of the P leached at the high P sites was mainly due to desorption and
      dissolution of weakly adsorbed P from prior P applications. This was consistent
      with P transport simulations using the convective-dispersive equation. We
      conclude that P concentration in land-applied wastewater should be regulated
      based on soil test-P level plus wastewater P loading.

PMID- 15998850
TI  - Nitrate reduction in the presence of wustite .
AB  - Recent strategies to reduce elevated nitrate concentrations employ metallic Fe0
      as a reductant. Secondary products of Fe0 corrosion include magnetite (Fe3O4),
      green rust [Fe6(OH)12SO4], and wustite [FeO(s)]. To our knowledge, no studies
      have been reported on the reactivity of NO3- with FeO(s). This project was
      initiated to evaluate the reactivity of FeO(s) with NO3- under abiotic
      conditions. Stirred batch reactions were performed in an anaerobic chamber over a
      range of pH values (5.45, 6.45, and 7.45), initial FeO(s) concentrations (1, 5,
      and 10 g L(-1)), initial NO3- concentrations (1, 10, and 15 mM), and temperatures
      (3, 21, 31, and 41 degrees C) for kinetic and thermodynamic determinations.
      Suspensions were periodically removed and filtered to measure dissolved nitrogen
      and iron species. Solid phases were characterized using X-ray diffraction (XRD)
      and scanning electron microscopy (SEM). Nitrate reduction by FeO was rapid and
      characterized by nearly stoichiometric conversion of NO3- to NH4+. Transient NO2-
      formation also occurred. The XRD and SEM results indicated the formation of Fe3O4
      as a reaction product of the heterogeneous redox reaction. Kinetics of NO3-
      reduction suggested a rate equation of the type: -d[NO3-]/dt =
      k[FeO]0.57[H]0.22[NO3-]1.12 where k = 3.46 x 10(-3) +/- 0.38 x 10(-3) M(-1) s(
      1), at 25 degrees C. Arrhenius and Eyring plots indicate that the reaction is
      surface chemical-controlled and proceeds by an associative mechanism involving a
      step where both NO3- and FeO(s) bind together in an intermediate complex.

PMID- 15998851
TI  - Accelerated weathering of biosolid-amended copper mine tailings.
AB  - Application of municipal biosolids to mine tailings can enhance revegetation
      success, but may cause adverse environmental impacts, such as increased leaching
      of NO3- and metals to ground water. Kinetic weathering cells were used to
      simulate geochemical weathering to determine the effects of biosolid amendment on
      (i) pH of leachate and tailings, (ii) leaching of NO3- and SO4(2-), (iii)
      leaching and bioavailability (DTPA-extractable) of selected metals, and (iv)
      changes in tailing mineralogy. Four Cu mine tailings from southern Arizona
      differing in initial pH (3.3-7.3) and degree of weathering were packed into
      triplicate weathering cells and were unamended and amended with two rates
      (equivalent to 134 and 200 Mg dry matter ha(-1)) of biosolids. Biosolid
      application to acid (pH 3.3) tailings resulted in pH values as high as 6.3 and
      leachate pH as high as 5.7, and biosolids applied to circumneutral tailings
      resulted in no change in tailing or leachate pH. Concentrations of NO3--N of up
      to 23 mg L(-1) occurred in leachates from circumneutral tailings. The low pH of
      the acidic tailing apparently inhibited nitrification, resulting in leachate NO3-
      N of <5 mg L(-1). Less SO4(2-)-S was leached in biosolid-amended versus unamended
      acid tailings (final rate of 0.04 compared with 0.11 g SO4(2-)-S wk(-1)). Copper
      concentrations in leachates from acidic tailings were reduced from 53 to 27 mg L(
      1) with biosolid amendment. Copper and As concentrations increased slightly in
      leachates from biosolid-amended circumneutral tailings. Small increases in DTPA
      extractable Cu, Ni, and Zn occurred in all tailings with increased biosolid rate.
      Overall, there was little evidence of potential for adverse environmental impacts
      resulting from biosolid application to these Cu mine tailings.

PMID- 15998852
TI  - Soil redistribution model for undisturbed and cultivated sites based on Chernobyl
      derived cesium-137 fallout.
AB  - Measurements of 137Cs fallout have been used in combination with a range of
      conversion models for the investigation of soil relocation mechanisms and
      sediment budgets in many countries for more than 20 yr. The objective of this
      paper is to develop a conversion model for quantifying soil redistribution, based
      on Chernobyl-derived 137Cs. The model is applicable on uncultivated as well as on
      cultivated sites, taking into account temporal changes in the 137Cs depth
      distribution pattern as well as tillage-induced 137Cs dilution effects. The main
      idea of the new model is the combination of a modified exponential model
      describing uncultivated soil with a Chapman distribution based model describing
      cultivated soil. The compound model subsequently allows a dynamic description of
      the Chernobyl derived 137Cs situation in the soil and its change, specifically
      migration and soil transport processes over the course of time. Using the
      suggested model at the sampling site in Pettenbach, in the Austrian province of
      Oberosterreich 137Cs depth distributions were simulated with a correlation
      coefficient of 0.97 compared with the measured 137Cs depth profile. The simulated
      rates of soil distribution at different positions at the sampling site were found
      to be between 27 and 60 Mg ha(-1) yr(-1). It was shown that the model can be used
      to describe the temporal changes of 137Cs depth distributions in cultivated as
      well as uncultivated soils. Additionally, the model allows to quantify soil
      redistribution in good correspondence with already existing models.

PMID- 15998853
TI  - Quantification of intrinsic water use efficiency along a moisture gradient in
      Northeastern China.
AB  - Water use efficiency (WUE) is an important ecophysiological characteristic of
      plants, especially in semiarid and arid regions. At the scale of community or
      ecosystem, WUE is difficult to quantify because the amount of water used per unit
      dry mass production is a function of microclimatic variables and species
      composition. In this study, we analyzed corrected intrinsic water use efficiency
      (IWUE(s)) of grass and shrub species along the western segment of the Northeast
      China Transect (NECT) and the relationship between IWUE(s) and mean annual
      rainfall, habitat degradation status, vegetation type, and plant functional type
      (C3 versus C4) at 22 survey sites. Site intrinsic water use efficiency (IWUE(v))
      and its relationship with the aforementioned site variables were analyzed based
      on species frequencies at each site. First, it was concluded that photosynthetic
      pathway played a very important role in determining species IWUE(s). Mean IWUE(s)
      for C4 species was approximately double that of C3 species. Second, mean annual
      rainfall, vegetation type, and site degradation status significantly affected
      IWUE(s) (p < 0.01). Mean IWUE(s) at degraded sites was twice as high as that at
      nondegraded sites. The mean IWUE(s) for meadows was significantly higher than
      those for other vegetation types (p < 0.05). Third, the frequency of occurrence
      of C4 plants explained 36% of the variance in IWUE(v) across the survey sites.
      The mean frequency of C4 occurrence at degraded sites was more than double that
      at nondegraded sites. Consequently, mean IWUE(v) at degraded sites was more than
      double that at nondegraded sites. Dominant C4 species in saline-alkaline areas
      tended to have higher intrinsic WUE than dominant C4 species in sandy shrub
      communities.

PMID- 15998854
TI  - White spruce response to co-composted hydrocarbon-contaminated drilling waste:
      effects of compost age and nitrogen fertilization.
AB  - There are growing interests to use co-composted drilling wastes contaminated with
      hydrocarbons as growth media for planting in land reclamation. However, such use
      of the compost may have potential problems such as inherent toxicity of residual
      hydrocarbon and microbial N immobilization due to high compost C to N ratios. We
      investigated the growth, biomass production, N uptake, and foliar delta13C of
      white spruce (Picea glauca [Moench] Voss) seedlings in a pot experiment using 1-,
      2-, 3-, and 4-yr-old composts (with different hydrocarbon concentrations and C to
      N ratios) and a local noncontaminated soil with (200 kg N ha(-1)) or without N
      fertilization. Growth and N content of seedlings (particularly N content in
      roots) were lower when grown in the compost media as compared with those grown in
      the soil. Within the compost treatments seedling growth was affected by compost
      age, but the magnitude of growth reduction was not linearly proportional to
      hydrocarbon concentrations. Plant N uptake increased with compost age, which
      corresponds with an increase in indigenous mineral N concentration. Effects of N
      fertilization on N uptake were curtailed by the presence of indigenous mineral N
      (e.g., in the 4-yr-old compost) and by fertilization-induced stimulation of
      microbial activities (e.g., in the 1-yr-old compost). The differences in foliar
      delta13C values between seedlings grown in compost and soil (P < 0.05) suggest
      that limitations on water uptake caused by the residual hydrocarbon might have
      been the predominant factor limiting seedling growth in the compost media. This
      study suggests that water stress caused by residual hydrocarbons may be a
      critical factor for the successful use of co-composted drilling wastes as a
      growth medium.

PMID- 15998855
TI  - Bioluminescent bacteria as indicators of chemical contamination of coastal
      waters.
AB  - The ratio of bioluminescent to total bacteria (bioluminescent ratio, BLR) as an
      indicator of a variety of types of anthropogenic contamination of estuarine
      ecosystems was evaluated through a series of laboratory and field studies.
      Laboratory studies indicated that the BLR of natural bacterioplankton communities
      was proportionally reduced in the presence of a number of contaminants including
      diesel fuel and saltmarsh sediments co-contaminated with mercury and
      polychlorinated biphenyls (PCBs). Bioluminescent ratio inhibition was observed
      after short-term exposure to a contaminant suggesting a physiological rather than
      a population response of native microbial communities. Simulated eutrophication
      did not suppress the BLR. Field observations of the BLR were conducted weekly for
      a 2-yr period in the Skidaway River estuary, Georgia, USA. These observations
      revealed considerable seasonal variability associated with the BLR.
      Bioluminescent ratios were highest during the summer (25 +/- 15%), lower in the
      fall (6 +/- 5%) and spring (3 +/- 2%), and near zero during the winter. Although
      the BLR was not significantly correlated to salinity at a single site (Skidaway
      River estuary), the BLR was significantly correlated with salinity when sites
      within the same estuary system were compared (r2 = 0.93). Variation in BLR was
      not correlated to standard bacteriological indicators of water quality including
      total and fecal coliform bacteria. Comparison of the BLR from impacted and
      pristine estuarine sites during the fall suggested that anthropogenically
      impacted sites exhibited lower BLR than predicted from salinity versus BLR
      relationships developed in pristine systems. These observations suggest that the
      BLR could be used as a simple and reliable initial indicator of chemical
      contamination of estuarine systems resulting from human activity.

PMID- 15998856
TI  - Residue level and manure application timing effects on runoff and sediment
      losses.
AB  - There is growing interest in evaluating the effects of corn silage harvesting
      methods on erosion control. Increasing the silage cutting height will increase
      residue cover and could conceivably minimize off-site migration of sediments
      compared with conventional silage harvesting. The effects of residue level and
      manure application timing on runoff and sediment losses from no-till corn were
      examined. Treatments included conventional corn grain (G) and silage (SL) and
      nonconventional, high-cut (60-65 cm) silage (SH). Corn harvesting treatments were
      subjected to different manure application regimes: no manure (N) or surface
      application in fall (F) or spring (S). Simulated rainfall (76 mm/h; 1 h) was
      applied in spring and fall for two years (2002-2003), runoff from 2.0- x 1.5-m
      plots collected, and a subsample analyzed for sediment concentration and
      aggregate size distribution. Runoff volume was inversely related to residue
      cover. Manure addition to silage plots reduced spring runoff by 71 to 88%,
      attributable to an increase in soil organic matter content, compared with SH-N
      and SL-N. Differences in sediment concentration between SH and SL were not
      significant. For silage plots, spring-applied manure had the greatest influence
      on sediment export reducing it by 84 to 93% in spring runoff compared with
      corresponding N plots. Sediment loads were also 85 to 97% lower from SH-S
      compared with SL-N in all four seasons. Except for spring 2003, sediment export
      was lower from G compared with SL. The combination of manure and higher residue
      associated with high-cut silage often lowered sediment export compared with low
      cut silage. Nearly identical aggregate size distributions were observed in
      sediments from SH and SL plots. High residue levels combined with spring-applied
      manure led to enrichment in the clay-sized fraction of runoff sediment. Recently
      applied manure and higher residue levels achieved by high-cutting silage can
      substantially lower sediment losses in spring runoff when soil is most
      susceptible to erosion.

PMID- 15998857
TI  - Predicting dissolved phosphorus in runoff from manured field plots.
AB  - Dissolved inorganic P transport in runoff from agricultural soils is an
      environmental concern. Models are used to predict P transport but rarely simulate
      P in runoff from surface-applied manures. Using field-plot data, we tested a
      previously proposed model to predict manure P in runoff. We updated the model to
      include more data relating water to manure ratio to manure P released during
      water extractions. We verified that this update can predict P release from manure
      to rain using published data. We tested the updated model using field-plot and
      soil-box data from three manure runoff studies. The model accurately predicted
      runoff P for boxes, but underpredicted runoff P for plots. Underpredictions were
      caused by runoff to rain ratios used to distribute P into runoff or infiltration.
      We developed P distribution fractions from manure water extraction data to
      replace runoff to rain ratios. Calculating P distribution fractions requires
      knowing rainfall rate and times that runoff begins and rain stops. Using P
      distribution fractions gave accurate predictions of runoff P for soil boxes and
      field plots. We observed relationships between measured runoff to rain ratios and
      both P distribution fractions and a degree of error in original predictions,
      calculated as (measured runoff P/predicted runoff P). Using independent field
      plot data, we verified that original underpredictions of manure runoff P can be
      improved by calculating P distribution fractions from measured runoff to rain
      ratios or adjusting runoff to rain ratios based on their degree of error. Future
      work should test the model at field or watershed scales and at longer time
      scales.

PMID- 15998858
TI  - Fertilizer, tillage, and dairy manure contributions to nitrate and herbicide
      leaching.
AB  - Few studies have examined the water quality impact of manure use in no-tillage
      systems. A lysimeter study in continuous corn (Zea mays L.) was performed on
      Maury silt loam (fine, mixed, semiactive, mesic Typic Paleudalf) to evaluate the
      effect(s) of tillage (no-till [NT] and chisel-disk [CD]), nitrogen fertilizer
      rate (0 and 168 kg N ha(-1)), and dairy manure application timing (none, spring,
      fall, or fall plus spring) on NO3-N, atrazine (2-chloro-4-ethylamino-6
      isopropylamino-s-triazine), and alachlor [2-chloro-2'-6'-diethyl-N
      (methoxymethyl)acetanilide] concentrations in leachate collected at a 90-cm
      depth. Herbicides were highest immediately after application, declining to less
      than 4 mug L(-1) in about two months. Manure and manure timing by tillage
      interactions had little effect on leachate herbicides; rather, the data suggest
      that macropores rapidly transmitted atrazine and alachlor through the soil.
      Tillage usually did not significantly affect leachate NO3-N, but no-tillage
      tended to cause higher NO(3)-N. Manuring caused higher NO3-N concentrations;
      spring manuring had more impact than fall, but fall manure contained about 78% of
      the N found in spring manure. Nitrate under spring "only fertilizer" treatment
      exceeded 10 mg L(-1) 38% of the time, compared with 15% for spring only manure
      treatment. After three years, manured soil leachate NO3-N exceeded that for soil
      receiving only N fertilizer. Soil profile (90 cm) NO3-N after corn harvest
      exceeding 22 kg N ha(-1) was associated with winter leachate NO3-N greater than
      10 mg N L(-1). Manure can be used effectively in conservation tillage systems on
      this and similar soils. Accounting for all N inputs, including previous manure
      applications, will be important.

PMID- 15998859
TI  - Surface runoff and transport of sulfonamide antibiotics and tracers on manured
      grassland.
AB  - Despite their common use in animal production the environmental fate of the
      veterinary sulfonamide antibiotics after excretion is only poorly understood. We
      performed irrigation experiments to investigate the transport of these substances
      with surface runoff on grassland. Liquid manure from pigs treated with
      sulfadimidine was spiked with sulfadiazine, sulfathiazole, the herbicide atrazine
      (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine), and the conservative
      tracer bromide and spread onto eight plots. Four plots received the same amounts
      of the spiked substances in aqueous solution (controls). Apart from the
      application matrix we varied the time between application and irrigation. Manure
      increased the runoff volume up to six times compared with the controls. It seemed
      that manure enhanced the runoff by sealing the soil surface. On manured plots the
      relative antibiotic concentrations in runoff were higher than on the controls,
      reaching an average of 0.3% (sulfadiazine), 0.8% (sulfathiazole), and 1.4%
      (sulfadimidine) of the input concentrations after a 1-d contact time. The
      corresponding values on the controls were 0.16% for sulfadiazine and 0.08% for
      sulfathiazole. After 3 d, the maximum values on the manured plots were even
      higher, whereas they had fallen below the limit of quantification on the
      controls. As a consequence, the sulfonamide losses were 10 to 40 times larger on
      the manured plots. The relative mobility of the sulfonamides on the control plots
      followed the trend expected from their chromatographic separation but the
      opposite was found on the manured plots. Hence it is important to consider
      explicitly the physical and chemical effects of manure when assessing the
      environmental fate of sulfonamides.

PMID- 15998860
TI  - Sorption, mobility, and transformation of estrogenic hormones in natural soil.
AB  - Potent estrogenic hormones are consistently detected in the environment at low
      concentration, yet these chemicals are strongly sorbed to soil and are labile.
      The objective of this research was to improve the understanding of the processes
      of sorption, mobility, and transformation for estrogens in natural soils, and
      their interaction. Equilibrium and kinetic batch sorption experiments, and a long
      term column study were used to study the fate and transport of 17beta-estradiol
      and its primary metabolite, estrone, in natural soil. Kinetic and equilibrium
      batch experiments were done using radiolabeled 17beta-estradiol and estrone. At
      the concentrations used, it appeared that equilibrium sorption for both estrogens
      was achieved between 5 and 24 h, and that the equilibrium sorption isotherms were
      linear. The log K(oc) values for 17beta-estradiol (2.94) and estrone (2.99) were
      consistent with previously reported values. Additionally, it was found that there
      was rate-limited sorption for both 17beta-estradiol (0.178 h(-1)) and estrone
      (0.210 h(-1)). An approximately 42 h long, steady-flow, saturated column
      experiment was used to study the transport of radiolabeled 17beta-estradiol,
      which was applied in a 5.00 mg L(-1) solution pulse for 44 pore volumes. 17beta
      estradiol and estrone were the predominant compounds detected in the effluent.
      The effluent breakthrough curves were asymmetric and the transport modeling
      indicated that sorption was rate-limited. Sorption rates and distributions of the
      estrogens were in agreement between column and batch experiments. This research
      can provide a better link between the laboratory results and observations in the
      natural environment.

PMID- 15998861
TI  - Establishing a linkage between phosphorus forms in dairy diets, feces, and
      manures.
AB  - Effective manure management to efficiently utilize organic wastes without causing
      environmental degradation requires a clear understanding of the transformation of
      P forms from diet to manure. Thus, the objective of this study was to establish
      quantitative relationships between P forms in diets, feces, and manures collected
      from U.S. Northeastern and Mid-Atlantic commercial dairy farms. Total P in diets
      ranged from 3.6 to 5.3 g kg(-1) dry matter, while the feces had higher P than
      diets (5.7-9.5 g kg(-1)) and manures had lower P (2.5-8.9 g kg(-1)) than feces.
      The farms with total dietary P of 4.8 to 5.3 g P kg(-1) had twofold higher
      concentrations of phytic acid (1647-2300 mg P kg(-1)) than farms with 3.6 to 4.0
      g dietary P kg(-1) (844-1100 mg P kg(-1)). Much of the phytic acid in diets was
      converted to inorganic orthophosphate in the rumen as indicated by a reduction in
      phytic acid percentage from diets (32%) to feces (18%). The proportion of
      orthophosphate diesters (phospholipids, deoxyribonucleic acid [DNA]) was twice as
      high in feces (6.2-10%) as diets (2.4-5.3%) suggesting the excretion of microbial
      residues in feces. Phosphonates (aminoethyl phosphonates and phosphonolipids)
      were not seen in diets but were detected in feces and persisted in manures, which
      suggests a microbial origin. These organic compounds (phytic acid, phospholipids,
      DNA) were decomposed on storage of feces in slurry pits, increasing
      orthophosphate in manures by 9 to 12% of total P. These results suggest that
      reducing dietary P and typically storing feces in dairy farms will result in
      manure with similar chemical forms (primarily orthophosphate: 63-77%) that will
      be land applied. Thus, both the reduction of dietary P and storage of manure on
      farm are important for controlling solubility and bioavailability of P forms in
      soils and waters.

PMID- 15998862
TI  - Physicochemical characteristics of animal and municipal wastes decomposed in arid
      soils.
AB  - The application of anaerobically processed animal manure to maintain adequate
      levels of organic matter in arid soils is becoming a common practice. The purpose
      of this study was to characterize two farm manure products as compared with
      municipal waste compost (MWC). The anaerobic processing to obtain a biogas manure
      (BM) product was much faster (25 d) than the aerobic composting of farmyard
      manure (FYM) (90 d). Drying by three different methods (solar-drying, vacuum
      drying at 45 degrees C, and freeze-drying) did not affect the quality of BM.
      Based on the chemical characteristics, FYM and BM products were comparable, and,
      containing less ash (30%) and heavy metals (50 mg Pb kg(-1)), seemed superior to
      MWC that contained 65% ash and 108 mg Pb kg(-1). On the other hand, MWC had
      higher C content (69.9%), lower acidity (15.04 mol kg(-1)), and higher exothermic
      peaks (300-460 degrees C) than BM and FYM (50% C, 20 mol kg(-1), and 275-450
      degrees C, respectively), thus showing a greater extent of humification. Also,
      when the organic materials were incubated with arid soils and monitored for mean
      residence times (MRT), MWC was slightly more resistant to decomposition (MRT 175
      180 d) than BM or FYM (MRT 161-166 d). The observed differences, however, were
      too small to dismiss any of the products as a valuable material for land
      applications to improve soil quality. In view of the results obtained, MWC may be
      considered an adequate substitute for BM or FYM, whenever the latter are in short
      supply.

PMID- 15998863
TI  - Enhanced radionuclide immobilization and flow path modifications by dissolution
      and secondary precipitates.
AB  - Caustic radioactive wastes that have leaked at Hanford Site (Richland, WA) induce
      mineral dissolution and subsequent secondary precipitation that influence the
      fate and transport of contaminants present in the waste solutions. The effects of
      secondary mineral precipitates, formed after contacting solids with simulated
      caustic wastes, on the flow path changes and radionuclide immobilization were
      investigated by reacting quartz, a mixture of quartz and biotite, and a Hanford
      sediment (Warden soil: coarse-silty, mixed, superactive, mesic Xeric
      Haplocambids) with simulated caustic tank waste solution. Continuous Si
      dissolution and concomitant secondary mineral precipitation were the principal
      reactions observed in both batch and flow-through tests. Nitrate-cancrinite was
      the dominant secondary precipitate on mineral surfaces after 3- to 10-d reaction
      times in batch experiments. X-ray microtomography images of a reacted quartz
      column revealed that secondary precipitates cemented quartz grains together and
      modified pore geometry in the center of the column. Along the circumference of
      the packed column, however, quartz dissolution continuously occurred, suggesting
      that wastes that leaked from buried tanks in the past likely did not migrate
      vertically as modeled in risk assessments but rather the pathways likely changed
      to be dominantly horizontal on precipitation of secondary precipitate phases in
      the Hanford vadose zone. Based on batch equilibrium sorption results on the
      reacted sediments, the dominant secondary precipitates (cancrinites) on the
      mineral surfaces enhanced the sorption capacity of typical Hanford sediment for
      radionuclides 129I(-I), 79Se(VI), 99Tc(VII), and 90Sr(II), all of which are of
      major concern at the Hanford Site.

PMID- 15998864
TI  - Impact of soil amendments on reducing phosphorus losses from runoff in sod.
AB  - Received for publication December 22, 2004. Research was initiated to study the
      interaction between soil amendments (lime, gypsum, and ferrous sulfate) and
      dissolved molybdate reactive phosphorus [RP(<0.45)] losses from manure
      applications from concentrated runoff flow through a sod surface. Four run-over
      boxes (2.2-m2 surface area) were prepared for each treatment with a bermudagrass
      [Cynodon dactylon (L.) Pers.] sod surface (using sod blocks) and composted dairy
      manure was surface-applied at rates of 0, 4.5, 9, or 13.5 Mg ha-1. The three soil
      amendments were then applied to the boxes. Two 30-min runoff events were
      conducted and runoff water was collected at 10-min intervals and analyzed for
      RP(<0.45). Results indicated that the addition of ferrous sulfate was very
      effective at reducing the level of RP(<0.45). in runoff water, reducing RP(<0.45)
      from 1.3 mg L(-1) for the highest compost rate with no amendment to 0.2 mg L(-1)
      for the ferrous sulfate in the first 10 min of runoff. Lime and gypsum showed a
      small impact on reducing RP(<0.45), with a reduction in the first 10 min to 0.9
      and 0.8 mg L(-1), respectively. The ferrous sulfate reduced the RP(<0.45) in the
      tank at the end of the first runoff event by 66.3% compared with no amendment. In
      the second runoff event, the ferrous sulfate was very effective at reducing
      RP(<0.45) in runoff, with no significant differences in RP(<0.45) with
      application of 13.5 Mg ha(-1) compost compared with no manure application. The
      results indicate that the addition of ferrous sulfate may greatly reduce
      RP(<0.45) losses in runoff and has considerable potential to be used on pasture,
      turfgrass, and filter strips to reduce the initial RP(<0.45) losses from manure
      application to the environment.

PMID- 15998865
TI  - Visible-near infrared reflectance spectroscopy for rapid, nondestructive
      assessment of wetland soil quality.
AB  - Recent evidence supports using visible-near infrared reflectance spectroscopy
      (VNIRS) for sensing soil quality; advantages include low-cost, nondestructive,
      rapid analysis that retains high analytical accuracy for numerous soil
      performance measures. Research has primarily targeted agricultural applications
      (precision agriculture, performance diagnostics), but implications for assessing
      ecological systems are equally significant. Our objective was to extend
      chemometrics for sensing soil quality to wetlands. Hydric soils posed two
      challenges. First, wetland soils exhibit a wider range of organic matter
      concentrations, particularly in riparian areas where levels range from <1% in
      sedimentation zones to >90% in backwater floodplains; this may mute spectral
      responses from other soil fractions. Second, spectral inference of cation
      concentrations in terrestrial soils is for oxidized species; under reducing
      conditions in wetlands, oxidation state variability is observed, which strongly
      affects chroma. Riparian soils (n = 273) from western Florida exhibiting
      substantial target parameter variability were compiled. After minimal pre
      processing, soils were scanned under artificial illumination using a laboratory
      spectrometer. A multivariate data mining technique (regression trees) was used to
      relate post-processed reflectance spectra to laboratory observations (pH, organic
      content, cation concentrations, total N, C, and P, extracellular enzyme
      activity). High validation accuracy was generally observed (r2(validation) > 0.8,
      RPD > 2.0, where RPD is the ratio of the standard deviation of an attribute to
      the observed standard error of validation); where accuracy was lower, categorical
      models (classification trees) successfully screened samples based on diagnostic
      functional thresholds (validation odds ratio > 10). Graphical models verified
      significant association between predictions and observations for all parameters,
      conditioning on biogeochemical covariates. Visible-near infrared reflectance
      spectroscopy offers both cost and statistical power advantages; hydric conditions
      do not appear to constrain application.

PMID- 15998866
TI  - Reductive dechlorination of tetrachloroethene in a sand reactor using a
      potentiostat.
AB  - In this study, an electrochemical system was investigated to enhance abiotic
      dechlorination of chlorinated solvents in contaminated soil in situ. A
      potentiostatic electrolysis sand reactor was developed and tested to evaluate
      tetrachloroethene (PCE) dechlorination in saturated sand. When operated with
      recirculating nutrient-supplemented water the reactor sustained a low oxidation
      reduction potential (ORP) at the cathode (<-400 mV standard hydrogen electrode
      [SHE]), a pH less than 9.4, and electric current >5 mA at room temperature with
      the cathodic potential controlled at -950 mV SHE. Tetrachloroethene in the
      electrolysis reactor had a half-life of 6.8 d compared with the control
      bioreactor without electrolysis, which had a PCE half-life of 16.4 d. Ethane and
      ethene were the main dechlorination products in the test reactor, while
      trichloroethene (TCE) accumulated in the nutrient-amended control reactor without
      electrolysis. An electrolysis reactor operated with water not amended with
      nutrients showed a PCE half-life of 7.6 d, suggesting that most of dechlorination
      activity in the reactor was abiotic. Since complete dechlorination can be
      achieved under moderate pH and temperature, this type of electrolysis technology
      is attractive as a remedial method for subsurface chloroethene contamination.

PMID- 15998868
TI  - Disturbance of water-extractable phosphorus determination by colloidal particles
      in a heavy clay soil from the Netherlands.
AB  - Water extraction methods are widely used to extract phosphorus (P) from soils for
      both agronomic and environmental purposes. Both the presence of soil colloids in
      soil water filtrates, and the contribution of colloidal P to the molybdate
      reactive phosphorus (MRP) concentration measured in these filtrates, are well
      documented. However, relatively little attention has been given to the direct
      disturbance by colloids of MRP measurement. The objective of this paper is to
      show this influence found for water extracts with a soil to solution ratio of
      1:60 (v/v) (P(w)), obtained from a heavy clay soil in the Netherlands. Colloidal
      particles, which passed a 0.45-mum filter, caused a large overestimation of MRP.
      The low ionic strength of the P(w) filtrates (on average 0.64 mmol(c) L(-1))
      probably caused soil dispersion and increased detachment of colloids from soil
      during extraction. After NaCl addition, followed by 0.45-mum filtration, MRP was
      on average 93% lower. This can be ascribed to flocculation of colloids and
      removal by filtration. A low ionic strength can thus lead to the direct
      disturbance by colloidal particles of MRP measurement in waters from soils
      sensitive to release of colloids.

PMID- 15998867
TI  - Influence of canola and sunflower diet amendments on cattle feedlot manure.
AB  - Cattle (Bos taurus) producers can replace a part of the traditional diet of
      barley (Hordeum vulgare L.) grain/silage with sunflower (Helianthus annus L.)
      seeds or canola meal (Brassica napus L.)/oil to enhance conjugated linoleic acids
      (CLA) content in milk and meat for its positive health benefits. The objective of
      this study is to investigate the effects of feeding sunflower or canola to
      finishing steers on cattle manure chemical properties and volatile fatty acid
      (VFA) content. The control diet contained 84% rolled barley and 15% barley
      silage, which provided only 2.6% lipid. The other six treatments had 6.6 to 8.6%
      lipid delivered from sources such as hay, sunflower seed (SS), canola meal/oil,
      and SS forage pellets. Manure samples (a mixture of cattle urine, feces, and
      woodchip bedding materials) were collected and analyzed after cattle had been on
      these diets for 113 d. The dietary source and level of lipid had no effect on
      organic N and nitrate N content in manure, but significantly affected ammonia N
      and VFA. Inclusion of SS forage pellets, hay, or canola meal/oil in cattle diets
      had no significant impact on manure characteristics, but SS significantly reduced
      the pH and increased propionic, isobutyric, and isovaleric content. In addition,
      N loss after excretion (mainly from urine N) increases with the pH and N levels
      in both feed and manure. The combination of SS with barley silage resulted in a
      lower VFA and NH3 content in manure and should be a more attractive option. To
      better manage N nutrient cycles and reduce NH3 related odor problems, feed and
      manure pH should be one of the factors to consider when determining feed mix
      rations.

PMID- 15998869
TI  - Signals from the past.
AB  - Science's STKE celebrates Science's 125th anniversary issue by presenting 12
      notable articles from Science that highlight different aspects of cell signaling
      research.

PMID- 15998871
TI  - That which does not kill you makes you stronger: a molecular mechanism for
      preconditioning.
AB  - Preconditioning by sublethal stress can protect a cell from subsequent injury and
      apoptosis through a mechanism that has been unclear. Many such stresses stimulate
      the formation of stress granules: transient cytoplasmic foci that contain heat
      shock protein as well as translationally stalled mRNA and various mRNA-binding
      proteins. Recent research suggests that sequestration in stress granules of
      TRAF2, an adaptor protein that is required for tumor necrosis factor receptor 1
      signaling, may underlie preconditioning by sublethal stresses.

PMID- 15998870
TI  - c-Src: bridging the gap between phosphorylation- and acidification-induced gap
      junction channel closure.
AB  - Gap junctions are a unique type of intercellular junction that mediate the direct
      exchange of small molecules between neighboring cells and play critical roles in
      the normal function of numerous organs. Mutations in the connexin proteins that
      make up gap junctions have been implicated in numerous human skin and
      neurosensory disorders. The ability of gap junctions to transmit molecules
      between cells is regulated by intracellular pH, the phosphorylation state of
      connexin, and the interaction of connexin with other cellular proteins. This
      Perspective focuses on the novel and complex events initiated by intracellular
      acidification resulting from tissue ischemia or hypoxia that lead to the
      interruption of intercellular communication between astrocytes. These events
      include alterations in connexin43 (Cx43) phosphorylation, disruption of beta
      actin binding to Cx43, and the induced interaction of Cx43 with the c-Src
      tyrosine kinase, extracellular signal-regulated kinase 1 and 2, and mitogen
      activated protein kinase phosphatase 1.

PMID- 15998872
TI  - Overexpression of Rad23 confers resistance to methylmercury in saccharomyces
      cerevisiae via inhibition of the degradation of ubiquitinated proteins.
AB  - We report here that overexpression of Rad23, a protein related to the ubiquitin
      proteasome system, renders yeast cells resistant to methylmercury. Rad23 has
      three domains: two ubiquitin-associated (UBA) domains that bind to the
      multiubiquitin chain of ubiquitinated proteins and a single ubiquitin-like (UbL)
      domain that binds to proteasomes. To examine the mechanism of acquisition of
      methylmercury resistance that is induced by overexpression of Rad23, we expressed
      variants of Rad23 in which one or the other of the two types of domain was
      defective in yeast cells. In cells that overexpressed full-length intact Rad23,
      we detected elevated levels of intracellular ubiquitinated proteins, and the
      cells were resistant to methylmercury. In contrast, cells that overexpressed
      Rad23 with a defective UBA domain were not resistant to methylmercury and
      contained control levels of ubiquitinated proteins. Yeast cells that
      overexpressed Rad23 with a defective UbL domain exhibited enhanced resistance to
      methylmercury and contained even higher levels of ubiquitinated proteins than
      cells that overexpressed intact full-length Rad23. Rad23 is known to have two
      mutually contradictory functions. It suppresses the degradation of ubiquitinated
      proteins by proteasomes via a mechanism mediated by the UBA domains, and it
      enhances the degradation of ubiquitinated proteins via a mechanism that is
      mediated by the UbL domain. Therefore, our findings suggest that Rad23 might
      induce resistance to methylmercury in yeast cells by suppressing the degradation
      of proteins that reduce the toxicity of methylmercury via a UBA domain-mediated
      mechanism.

PMID- 15998874
TI  - The Cover. Construction for noble ladies.

PMID- 15998873
TI  - Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through
      estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen
      activated protein kinase pathways in osteoblasts.
AB  - Diosgenin, extracted from the root of wild yam (Dioscorea villosa), has been
      reported to demonstrate an opportunity for medical application. Vascular
      endothelial growth factor-A (VEGF-A) plays an important role in bone-related
      angiogenesis, a critical process occurring during bone formation and fracture
      healing. In this study, we examine whether diosgenin is able to induce VEGF-A
      expression and to promote angiogenesis in osteoblasts. For murine MC3T3-E1
      preosteoblast-like cells, VEGF-A mRNA and protein expression seemed to be
      significantly elevated in response to diosgenin in a concentration-dependent
      fashion. Conditioned media prepared from cells treated with diosgenin induced
      strong angiogenic activity in either in vitro or ex vivo angiogenesis assay.
      Furthermore, diosgenin treatment increased the stability and activity of HIF
      1alpha protein. Inhibition of HIF-1alpha activity by transfection with DN-HIF
      1alpha significantly diminished diosgenin-mediated VEGF-A up-regulation. The use
      of pharmacological inhibitors or genetic inhibition revealed that both the
      phosphatidylinositol 3-kinase (PI3K)/Akt and p38 signaling pathways were
      potentially required for diosgenin-induced HIF-1 activation and subsequent VEGF-A
      up-regulation. It is noteworthy that an estrogen receptor binding assay revealed
      that diosgenin has the strong ability to replace [(3)H]estradiol bound to
      estrogen receptor (IC(50), 10 nM). In addition, the specific estrogen receptor
      antagonists ICI 182,780 (faslodex) and tamoxifen were noted to be able to
      strongly inhibit diosgenin-induced, src kinase-dependent Akt and p38 MAPK
      activation. Taken together, such results provide evidence that diosgenin up
      regulates VEGF-A and promotes angiogenesis in preosteoblast-like cells by a
      hypoxia-inducible factor-1alpha-dependent mechanism involving the activation of
      src kinase, p38 MAPK, and Akt signaling pathways via estrogen receptor.

PMID- 15998875
TI  - A piece of my mind. Death and life in Iraq.

PMID- 15998876
TI  - Clinical trials point to complexities of chemoprevention for cancer.

PMID- 15998877
TI  - Inflammation suspected in eye disorders.

PMID- 15998878
TI  - Studies probe diet's role in eye disease.

PMID- 15998879
TI  - Woman gives birth after ovary transplant.

PMID- 15998880
TI  - Evidence-based guidelines needed for osteoporosis screening and treatment.

PMID- 15998883
TI  - Acting and clinical empathy.

PMID- 15998884
TI  - Acting and clinical empathy.

PMID- 15998885
TI  - Methodological standards in human vs animal clinical trials.

PMID- 15998886
TI  - Patient preference and validity of randomized controlled trials.

PMID- 15998887
TI  - Patient preference and validity of randomized controlled trials.

PMID- 15998888
TI  - Screening for psychological illness in the military.

PMID- 15998889
TI  - Single-payer health systems and statistics.

PMID- 15998890
TI  - Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a
      randomized controlled trial.
AB  - CONTEXT: Basic research and observational evidence as well as results from trials
      of colon polyp recurrence suggest a role for aspirin in the chemoprevention of
      cancer. OBJECTIVE: To examine the effect of aspirin on the risk of cancer among
      healthy women. DESIGN, SETTING, AND PARTICIPANTS: In the Women's Health Study, a
      randomized 2 x 2 factorial trial of aspirin and vitamin E conducted between
      September 1992 and March 2004, 39 876 US women aged at least 45 years and
      initially without previous history of cancer, cardiovascular disease, or other
      major chronic illness were randomly assigned to receive either aspirin or aspirin
      placebo and followed up for an average of 10.1 years. INTERVENTION: A dose of 100
      mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other
      day. MAIN OUTCOME MEASURES: Confirmed newly diagnosed invasive cancer at any
      site, except for nonmelanoma skin cancer. Incidence of breast, colorectal, and
      lung cancer were secondary end points. RESULTS: No effect of aspirin was observed
      on total cancer (n = 2865; relative risk [RR], 1.01; 95% confidence interval
      [CI], 0.94-1.08; P = .87), breast cancer (n = 1230; RR, 0.98; 95% CI, 0.87-1.09;
      P = .68), colorectal cancer (n = 269; RR, 0.97; 95% CI, 0.77-1.24; P = .83), or
      cancer of any other site, with the exception of lung cancer for which there was a
      trend toward reduction in risk (n = 205; RR, 0.78; 95% CI, 0.59-1.03; P = .08).
      There was also no reduction in cancer mortality either overall (n = 583; RR,
      0.95; 95% CI, 0.81-1.11; P = .51) or by site, except for lung cancer mortality (n
      = 140; RR, 0.70; 95% CI, 0.50-0.99; P = .04). No evidence of differential effects
      of aspirin by follow-up time or interaction with vitamin E was found.
      CONCLUSIONS: Results from this large-scale, long-term trial suggest that
      alternate day use of low-dose aspirin (100 mg) for an average 10 years of
      treatment does not lower risk of total, breast, colorectal, or other site
      specific cancers. A protective effect on lung cancer or a benefit of higher doses
      of aspirin cannot be ruled out.

PMID- 15998891
TI  - Vitamin E in the primary prevention of cardiovascular disease and cancer: the
      Women's Health Study: a randomized controlled trial.
AB  - CONTEXT: Basic research provides plausible mechanisms and observational studies
      suggest that apparently healthy persons, who self-select for high intakes of
      vitamin E through diet or supplements, have decreased risks of cardiovascular
      disease and cancer. Randomized trials do not generally support benefits of
      vitamin E, but there are few trials of long duration among initially healthy
      persons. OBJECTIVE: To test whether vitamin E supplementation decreases risks of
      cardiovascular disease and cancer among healthy women. DESIGN, SETTING, AND
      PARTICIPANTS: In the Women's Health Study conducted between 1992 and 2004, 39 876
      apparently healthy US women aged at least 45 years were randomly assigned to
      receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial
      design, and were followed up for an average of 10.1 years. INTERVENTION:
      Administration of 600 IU of natural-source vitamin E on alternate days. MAIN
      OUTCOME MEASURES: Primary outcomes were a composite end point of first major
      cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or
      cardiovascular death) and total invasive cancer. RESULTS: During follow-up, there
      were 482 major cardiovascular events in the vitamin E group and 517 in the
      placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95%
      confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects
      on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96)
      or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or
      hemorrhagic stroke. For cardiovascular death, there was a significant 24%
      reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect
      on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in
      the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95%
      CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon
      cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ
      significantly between groups. There was no significant effect of vitamin E on
      total mortality (636 in the vitamin E group and 615 in the placebo group; RR,
      1.04; 95% CI, 0.93-1.16; P = .53). CONCLUSIONS: The data from this large trial
      indicated that 600 IU of natural-source vitamin E taken every other day provided
      no overall benefit for major cardiovascular events or cancer, did not affect
      total mortality, and decreased cardiovascular mortality in healthy women. These
      data do not support recommending vitamin E supplementation for cardiovascular
      disease or cancer prevention among healthy women.

PMID- 15998892
TI  - Operating characteristics of prostate-specific antigen in men with an initial PSA
      level of 3.0 ng/ml or lower.
AB  - CONTEXT: Three fourths of US men older than 50 years have been screened with
      prostate-specific antigen (PSA) for prostate cancer. OBJECTIVE: To estimate the
      receiver operating characteristic (ROC) curve for PSA. DESIGN, SETTING, AND
      PARTICIPANTS: Calculation of PSA ROC curves in the placebo group of the Prostate
      Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to
      2003 at 221 US centers. Participants were 18 882 healthy men aged 55 years or
      older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL
      and normal digital rectal examination results, followed up for 7 years with
      annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0
      ng/mL or rectal examination result was abnormal, a prostate biopsy was
      recommended. After 7 years of study participation, an end-of-study prostate
      biopsy was recommended in all cancer-free men. MAIN OUTCOME MEASURES: Operating
      characteristics of PSA for prostate cancer detection, including sensitivity,
      specificity, and ROC curve. RESULTS: Of 8575 men in the placebo group with at
      least 1 PSA measurement and digital rectal examination in the same year, 5587
      (65.2%) had had at least 1 biopsy; of these, 1225 (21.9%) were diagnosed with
      prostate cancer. Of 1213 cancers with Gleason grade recorded, 250 (20.6%) were
      Gleason grade 7 or greater and 57 (4.7%) were Gleason grade 8 or greater. The
      areas under the ROC curve (AUC) for PSA to discriminate any prostate cancer vs no
      cancer, Gleason grade 7 or greater cancer vs no or lower-grade cancer, and
      Gleason grade 8 or greater cancer vs no or lower-grade cancer were 0.678 (95%
      confidence interval [CI], 0.666-0.689), 0.782 (95% CI, 0.748-0.816), and 0.827
      (95% CI, 0.761-0.893), respectively (all P values <.001 for AUC vs 50%). For
      detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL
      yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of
      38.9%, 72.5%, 86.7%, and 93.8%, respectively. Age-stratified analyses showed
      slightly better performance of PSA in men younger than 70 years vs those 70 years
      or older with AUC values of 0.699 (SD, 0.013) vs 0.663 (SD, 0.013) (P = .03).
      CONCLUSION: There is no cutpoint of PSA with simultaneous high sensitivity and
      high specificity for monitoring healthy men for prostate cancer, but rather a
      continuum of prostate cancer risk at all values of PSA.

PMID- 15998893
TI  - Thyroid function and mortality in patients treated for hyperthyroidism.
AB  - CONTEXT: Hyperthyroidism has been reported to cause excess all-cause and
      circulatory mortality. Whether this can be reversed is unknown, as is the
      influence of mild persisting thyroid dysfunction and treatment-induced
      hypothyroidism. OBJECTIVES: To determine whether radioiodine treatment is
      associated with increased mortality and to determine the influences of mild
      thyroid dysfunction and the development of overt hypothyroidism treated with
      thyroxine (T(4)). DESIGN, SETTING, AND PARTICIPANTS: A population-based study of
      2668 individuals aged 40 years or older treated for overt hyperthyroidism with
      radioiodine in the West Midlands region of England from 1984-2002. MAIN OUTCOME
      MEASURES: Cause of death compared with age- and period-specific mortality in
      England and Wales and assessment of the influence of T(4) therapy for radioiodine
      induced hypothyroidism and subclinical thyroid dysfunction on mortality. RESULTS:
      In 15,968 person-years of follow-up, 554 died vs 487 expected deaths
      (standardized mortality ratio [SMR], 1.14; 95% confidence interval [CI], 1.04
      1.24, P=.002). Increased risks of all-cause and circulatory deaths vs age- and
      period-specific mortality were observed in follow-up in those not requiring, or
      prior to, T(4) therapy. These increased risks were not observed during follow-up
      on T(4) therapy (circulatory disease SMR prior to T(4), 1.33; 95% CI, 1.14-1.53
      vs SMR, 0.91; 95% CI, 0.70-1.17 during T(4)). Patients receiving T(4) had
      decreased risk of mortality vs risk in the period not requiring, or prior to,
      T(4) therapy (all-cause mortality hazard ratio [HR], 0.65; 95% CI, 0.54-0.79;
      circulatory mortality HR, 0.65; 95% CI, 0.48-0.87). Increased all-cause mortality
      vs the background population was observed in the period prior to T(4) therapy in
      follow-up associated with low, normal, and high serum thyrotropin. The SMR for
      ischemic heart disease increased slightly when analyzed by serum thyrotropin,
      high serum thyrotropin being the highest SMR (low thyrotropin SMR, 1.06; 95% CI,
      0.75-1.45; normal thyrotropin SMR, 1.17; 95% CI, 0.76-1.71; high thyrotropin SMR,
      1.48; 95% CI, 0.86-2.37). Comparison within the cohort showed that mild
      hypothyroidism prior to T(4) therapy was associated with increased risk of
      mortality from ischemic heart disease vs biochemical euthyroidism (HR, 2.08; 95%
      CI, 1.04-4.19). CONCLUSIONS: Patients treated with radioiodine for
      hyperthyroidism had increased mortality vs age- and period-specific mortality in
      England and Wales, a finding no longer evident during T(4) therapy. This supports
      treating hyperthyroidism with doses of radioiodine sufficient to induce overt
      hypothyroidism. The association within the cohort of mortality from ischemic
      heart disease with subclinical hypothyroidism suggests T(4) replacement should be
      considered should this biochemical abnormality develop after radioiodine therapy.

PMID- 15998895
TI  - Circulating androgen levels and self-reported sexual function in women.
AB  - CONTEXT: It has been proposed that low sexual desire and sexual dysfunction are
      associated with low blood testosterone levels in women. However, evidence to
      support this is lacking. OBJECTIVE: To determine whether women with low self
      reported sexual desire and sexual satisfaction are more likely to have low serum
      androgen levels than women without self-reported low sexual desire and sexual
      satisfaction. DESIGN, SETTING, AND PARTICIPANTS: A community-based, cross
      sectional study of 1423 women aged 18 to 75 years, who were randomly recruited
      via the electoral roll in Victoria, Australia, from April 2002 to August 2003.
      Women were excluded from the analysis if they took psychiatric medication, had
      abnormal thyroid function, documented polycystic ovarian syndrome, or were
      younger than 45 years and using oral contraception. MAIN OUTCOME MEASURES: Domain
      scores of the Profile of Female Sexual Function (PFSF) and serum levels of total
      and free testosterone, androstenedione, and dehydroepiandrosterone sulfate.
      RESULTS: A total of 1021 individuals were included in the final analysis. No
      clinically significant relationships between having a low score for any PFSF
      domain and having a low serum total or free testosterone or androstenedione level
      was demonstrated. A low domain score for sexual responsiveness for women aged 45
      years or older was associated with higher odds of having a serum
      dehydroepiandrosterone sulfate level below the 10th percentile for this age group
      (odds ratio [OR], 3.90; 95% confidence interval [CI], 1.54-9.81; P = .004). For
      women aged 18 to 44 years, having a low domain score for sexual desire (OR, 3.86;
      95% CI, 1.27-11.67; P = .02), sexual arousal (OR, 6.39; 95% CI, 2.30-17.73;
      P<.001), and sexual responsiveness (OR, 6.59; 95% CI, 2.37-18.34; P<.001) was
      associated with having a dehydroepiandrosterone sulfate level below the 10th
      percentile. CONCLUSIONS: No single androgen level is predictive of low female
      sexual function, and the majority of women with low dehydroepiandrosterone
      sulfate levels did not have low sexual function.

PMID- 15998894
TI  - Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension,
      and mortality in sickle cell disease.
AB  - CONTEXT: Sickle cell disease is characterized by a state of nitric oxide
      resistance and limited bioavailability of l-arginine, the substrate for nitric
      oxide synthesis. We hypothesized that increased arginase activity and
      dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary
      hypertension, and patient outcomes. OBJECTIVE: To explore the role of arginase in
      sickle cell disease pathogenesis, pulmonary hypertension, and mortality. DESIGN:
      Plasma amino acid levels, plasma and erythrocyte arginase activities, and
      pulmonary hypertension status as measured by Doppler echocardiogram were
      prospectively obtained in outpatients with sickle cell disease. Patients were
      followed up for survival up to 49 months. SETTING: Urban tertiary care center and
      community clinics in the United States between February 2001 and March 2005.
      PARTICIPANTS: Two hundred twenty-eight patients with sickle cell disease, aged 18
      to 74 years, and 36 control participants. MAIN OUTCOME MEASURES: Plasma amino
      acid levels, plasma and erythrocyte arginase activities, diagnosis of pulmonary
      hypertension, and mortality. RESULTS: Plasma arginase activity was significantly
      elevated in patients with sickle cell disease, with highest activity found in
      patients with secondary pulmonary hypertension. Arginase activity correlated with
      the arginine-ornithine ratio, and lower ratios were associated with greater
      severity of pulmonary hypertension and with mortality in this population (risk
      ratio, 2.5; 95% confidence interval [CI], 1.2-5.2; P = .006). Global arginine
      bioavailability, characterized by the ratio of arginine to ornithine plus
      citrulline, was also strongly associated with mortality (risk ratio, 3.6; 95% CI,
      1.5-8.3; P<.001). Increased plasma arginase activity was correlated with
      increased intravascular hemolytic rate and, to a lesser extent, with markers of
      inflammation and soluble adhesion molecule levels. CONCLUSIONS: These data
      support a novel mechanism of disease in which hemolysis contributes to reduced
      nitric oxide bioavailability and endothelial dysfunction via release of
      erythrocyte arginase, which limits arginine bioavailability, and release of
      erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine to
      ornithine and arginine to ornithine plus citrulline are independently associated
      with pulmonary hypertension and increased mortality in patients with sickle cell
      disease.

PMID- 15998896
TI  - Coffee consumption and risk of type 2 diabetes: a systematic review.
AB  - CONTEXT: Emerging epidemiological evidence suggests that higher coffee
      consumption may reduce the risk of type 2 diabetes. OBJECTIVE: To examine the
      association between habitual coffee consumption and risk of type 2 diabetes and
      related outcomes. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE through
      January 2005 and examined the reference lists of the retrieved articles. Because
      this review focuses on studies of habitual coffee consumption and risk of type 2
      diabetes, we excluded studies of type 1 diabetes, animal studies, and studies of
      short-term exposure to coffee or caffeine, leaving 15 epidemiological studies
      (cohort or cross-sectional). DATA EXTRACTION: Information on study design,
      participant characteristics, measurement of coffee consumption and outcomes,
      adjustment for potential confounders, and estimates of associations was
      abstracted independently by 2 investigators. DATA SYNTHESIS: We identified 9
      cohort studies of coffee consumption and risk of type 2 diabetes, including 193
      473 participants and 8394 incident cases of type 2 diabetes, and calculated
      summary relative risks (RRs) using a random-effects model. The RR of type 2
      diabetes was 0.65 (95% confidence interval [CI], 0.54-0.78) for the highest
      (>or=6 or >or=7 cups per day) and 0.72 (95% CI, 0.62-0.83) for the second highest
      (4-6 cups per day) category of coffee consumption compared with the lowest
      consumption category (0 or <or=2 cups per day). These associations did not differ
      substantially by sex, obesity, or region (United States and Europe). In the cross
      sectional studies conducted in northern Europe, southern Europe, and Japan,
      higher coffee consumption was consistently associated with a lower prevalence of
      newly detected hyperglycemia, particularly postprandial hyperglycemia.
      CONCLUSIONS: This systematic review supports the hypothesis that habitual coffee
      consumption is associated with a substantially lower risk of type 2 diabetes.
      Longer-term intervention studies of coffee consumption and glucose metabolism are
      warranted to examine the mechanisms underlying the relationship between coffee
      consumption and type 2 diabetes.

PMID- 15998897
TI  - Low-dose aspirin and vitamin E: challenges and opportunities in cancer
      prevention.

PMID- 15998898
TI  - Vitamin E and cardiovascular health: does sex matter?

PMID- 15998899
TI  - Reporting conflicts of interest, financial aspects of research, and role of
      sponsors in funded studies.

PMID- 15998900
TI  - JAMA patient page. Hyperthyroidism.

PMID- 15998901
TI  - Neoadjuvant endocrine therapy for breast cancer: more questions than answers.

PMID- 15998902
TI  - Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a
      North Central Cancer Treatment Group Study.
AB  - BACKGROUND: Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian
      target of rapamycin (mTOR) and represents a rational therapeutic target against
      glioblastoma multiforme (GBM). METHODS: Recurrent GBM patients with < or = 1
      chemotherapy regimen for progressive disease were eligible. Temsirolimus was
      administered in a 250-mg intravenous dose weekly. RESULTS: Sixty-five patients
      were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%,
      and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%),
      and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of
      patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area
      under the concentration-time curve were decreased in patients receiving p450
      enzyme-inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but
      were still within the therapeutic range of preclinical models. Twenty patients
      (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2
      signal abnormality +/- decrease in T1 gadolinium enhancement, on stable or
      reduced steroid doses. Progression-free survival at 6 months was 7.8% and median
      overall survival was 4.4 months. Median time to progression (TTP) for all
      patients was 2.3 months and was significantly longer for responders (5.4 months)
      versus nonresponders (1.9 months). Development of grade 2 or higher
      hyperlipidemia in the first two treatment cycles was associated with a higher
      percentage of radiographic response (71% v 31%; P = .04). Significant correlation
      was observed between radiographic improvement and high levels of phosphorylated
      p70s6 kinase in baseline tumor samples (P = .04). CONCLUSION: Temsirolimus is
      well tolerated in recurrent GBM patients. Despite the effect of EIACs on
      temsirolimus metabolism, therapeutic levels were achieved. Radiographic
      improvement was observed in 36% of temsirolimus-treated patients, and was
      associated with significantly longer TTP. High levels of phosphorylated p70s6
      kinase in baseline tumor samples appear to predict a patient population more
      likely to derive benefit from treatment. These findings should be validated in
      other studies of mTOR inhibitors.

PMID- 15998903
TI  - Neoadjuvant treatment of postmenopausal breast cancer with anastrozole,
      tamoxifen, or both in combination: the Immediate Preoperative Anastrozole,
      Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind
      randomized trial.
AB  - PURPOSE: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With
      Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical
      and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and
      with the combination of tamoxifen and anastrozole before surgery in
      postmenopausal women with estrogen receptor (ER) -positive, invasive,
      nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen
      Alone or in Combination (ATAC) adjuvant therapy trial. PATIENTS AND METHODS:
      Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or
      locally advanced potentially operable breast cancer were randomly assigned to
      neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination
      of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was
      assessed by both caliper and ultrasound. Comparisons were also made of clinical
      response with ultrasound response, actual and feasible surgery with feasible
      surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2)
      positive cancers, and tolerability. RESULTS: There were no significant
      differences in OR in the intent-to-treat population between patients receiving
      tamoxifen, anastrozole, or the combination. In patients who were assessed as
      requiring mastectomy at baseline (n = 124), 44% of patients received breast
      conserving surgery (BCS) after anastrozole compared with 31% of patients after
      tamoxifen (P = .23); this difference became significant for patients who were
      deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The
      OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole
      compared with 22% for tamoxifen (P = .18). All treatments were well tolerated.
      CONCLUSION: Neoadjuvant anastrozole is as effective and well tolerated as
      tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the
      hypothesis that clinical outcome might predict for long-term outcome in adjuvant
      therapy was not fulfilled.

PMID- 15998904
TI  - Targeting signal transduction pathways in colorectal cancer--more than skin deep.
AB  - Colorectal cancer is the second leading cause of cancer death in the United
      States. The nihilism that previously often characterized the treatment of
      patients with this disease has been replaced by a measure of excitement, given
      recent therapeutic advances. These advances have been stimulated in part through
      identification of cellular processes characteristic of colorectal cancers that
      permit therapeutic targeting with favorable therapeutic index. Inhibition of the
      epidermal growth factor receptor in the clinic has provided proof of principle
      that interruption of signal transduction cascades in patients with colorectal
      cancer has therapeutic potential. This experience has also taught us that
      resistance to such rationally developed targeted therapeutic strategies is
      common. In this article, we review the role of signal transduction in colorectal
      cancer, introduce promising molecular targets, and outline therapeutic approaches
      under development. We will describe the barriers to success, and highlight
      paradigms to facilitate rapid and successful evaluation of new agents, in a
      clinical context that has (by virtue of recent clinical successes) become a
      somewhat crowded playing field.

PMID- 15998905
TI  - Optimizing adjuvant endocrine therapy in postmenopausal women with early-stage
      breast cancer: a decision analysis.
AB  - PURPOSE: The optimal adjuvant endocrine strategy for postmenopausal breast cancer
      is unknown. Options include the antiestrogen tamoxifen, estrogen deprivation with
      aromatase inhibitors, and sequential therapy with tamoxifen and then an aromatase
      inhibitor. METHODS: We developed Markov models to simulate 10-year disease-free
      survival among postmenopausal women with hormone receptor-positive breast cancer.
      The treatment strategies analyzed were 5 years of tamoxifen alone, 5 years of an
      aromatase inhibitor alone, and sequential treatment consisting of tamoxifen with
      cross over to an aromatase inhibitor at 2.5 or 5 years. Risk estimates were
      derived from reported randomized clinical trials. RESULTS: Sequential therapy
      with tamoxifen followed by cross over to an aromatase inhibitor at 2.5 years
      yielded a modest improvement in disease-free survival compared with planned
      aromatase inhibitor monotherapy. At 10 years, the cross-over strategy yielded
      absolute disease-free survival rates of 83.7% and 67.6% for node-negative and
      node-positive patients, respectively, compared with 82.6% and 65.5%,
      respectively, for aromatase inhibitor monotherapy, which is a 6% relative risk
      reduction. Sequential therapy improved disease-free survival estimates by year 6
      after treatment initiation. Later cross over from tamoxifen to an aromatase
      inhibitor at 5 years did not further improve 10-year disease-free survival
      estimates. Sensitivity analyses suggest that sequential treatment strategies
      optimized 10-year disease-free and distant disease-free survival independent of
      the degree of the beneficial carryover effect after aromatase inhibitor therapy
      or the ratio of local to distant tumor recurrence. CONCLUSION: Modeling estimates
      suggest that sequential adjuvant therapy with tamoxifen followed by an aromatase
      inhibitor after 2.5 years yields improved outcomes compared with either drug
      alone or cross-over treatment after 5 years of tamoxifen.

PMID- 15998906
TI  - Increased epidermal growth factor receptor gene copy number detected by
      fluorescence in situ hybridization associates with increased sensitivity to
      gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest
      Oncology Group Study.
AB  - PURPOSE: Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features
      seem to be increasing in incidence, particularly in younger, never-smoking women.
      Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of
      20% to 30% in patients with advanced BAC subtypes, but selection methods for
      patient therapy are not established. PATIENTS AND METHODS: EGFR and HER2 gene
      copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81
      patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol
      S0126) and were correlated to treatment outcome. Tumors were classified into two
      main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative
      (disomy/low polysomy). RESULTS: In 81 patients, the median survival time for
      EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive
      patients (but approaching 18 months; hazard ratio [HR] = 2.02; P = .042). Median
      progression-free survival time for EGFR/FISH-positive patients was 9 months
      versus 4 months for the FISH-negative patients (HR = 1.67; P = .072). In
      multivariate analysis, EGFR copy number by FISH remained a significant predictive
      factor for survival after accounting for smoking status, sex, histology, and
      performance status. Fifty-five patients were evaluated for response using
      Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH
      positive patients (63%) demonstrated disease control versus 14 (39%) of 36
      patients in the FISH-negative group (P = .087). No association was found between
      HER2 gene copy number and response (n = 39 patients) or survival (n = 56
      patients; P > .10). CONCLUSION: Increased EGFR gene copy number detected by FISH
      is associated with improved survival after gefitinib therapy in patients with
      advanced BAC, suggesting FISH methodology can be used to assess survival
      potential in patients treated with EGFR tyrosine kinase inhibitors.

PMID- 15998907
TI  - Epidermal growth factor receptor gene mutations and increased copy numbers
      predict gefitinib sensitivity in patients with recurrent non-small-cell lung
      cancer.
AB  - PURPOSE: To evaluate epidermal growth factor receptor (EGFR) mutations and copy
      number as predictors of clinical outcome in patients with non-small-cell lung
      cancer (NSCLC) receiving gefitinib. PATIENTS AND METHODS: Sixty-six patients with
      NSCLC who experienced relapse after surgery and received gefitinib were included.
      Direct sequencing of exons 18 to 24 of EGFR and exons 18 to 24 of ERBB2 was
      performed using DNA extracted from surgical specimens. Pyrosequencing and
      quantitative real-time polymerase chain reaction were performed to analyze the
      allelic pattern and copy number of EGFR. RESULTS: Thirty-nine patients (59%) had
      EGFR mutations; 20 patients had deletional mutations in exon 19, 17 patients had
      missense mutations (L858R) in exon 21, and two patients had missense mutations
      (G719S or G719C) in exon 18. No mutations were identified in ERBB2. Response rate
      (82% [32 of 39 patients] v 11% [three of 27 patients]; P < .0001), time to
      progression (TTP; median, 12.6 v 1.7 months; P < .0001), and overall survival
      (median, 20.4 v 6.9 months; P = .0001) were significantly better in patients with
      EGFR mutations than in patients with wild-type EGFR. Increased EGFR copy numbers
      (> or = 3/cell) were observed in 29 patients (44%) and were significantly
      associated with a higher response rate (72% [21 of 29 patients] v 38% [14 of 37
      patients]; P = .005) and a longer TTP (median, 9.4 v 2.6 months; P = .038). High
      EGFR copy numbers (> or = 6/cell) were caused by selective amplification of
      mutant alleles. CONCLUSION: EGFR mutations and increased copy numbers were
      significantly associated with better clinical outcome in gefitinib-treated NSCLC
      patients.

PMID- 15998908
TI  - Identification of a missense mutation in the bovine ABCG2 gene with a major
      effect on the QTL on chromosome 6 affecting milk yield and composition in
      Holstein cattle.
AB  - We previously localized a quantitative trait locus (QTL) on chromosome 6
      affecting milk fat and protein concentration to a 4-cM confidence interval,
      centered on the microsatellite BM143. We characterized the genes and sequence
      variation in this region and identified common haplotypes spanning five
      polymorphic sites in the genes IBSP, SPP1, PKD2, and ABCG2 for two sires
      heterozygous for this QTL. Expression of SPP1 and ABCG2 in the bovine mammary
      gland increased from parturition through lactation. SPP1 and all the coding exons
      of ABCG2 and PKD2 were sequenced for these two sires. The single nucleotide
      change capable of encoding a substitution of tyrosine-581 to serine (Y581S) in
      the ABCG2 transporter was the only polymorphism corresponding to the segregation
      status of all 3 heterozygous and 15 homozygous sires for the QTL in the Israeli
      and U.S. Holstein populations. The allele substitution fixed effects on the
      genetic evaluations of 335 Israeli sires were -341 kg milk, +0.16% fat, and
      +0.13% protein (F-value = 200). No other polymorphism gave significant effect for
      fat and protein concentration in models that also included Y581S. The allele
      substitution effects on the genetic evaluations of 670 cows, daughters of two
      heterozygous sires, were -226 kg milk, 0.09% fat, and 0.08% protein (F-value =
      394), with partial dominance towards the 581S homozygotes. We therefore propose
      that Y581S in ABCG2 is the causative site for this QTL.

PMID- 15998909
TI  - Assessing the limits of genomic data integration for predicting protein networks.
AB  - Genomic data integration--the process of statistically combining diverse sources
      of information from functional genomics experiments to make large-scale
      predictions--is becoming increasingly prevalent. One might expect that this
      process should become progressively more powerful with the integration of more
      evidence. Here, we explore the limits of genomic data integration, assessing the
      degree to which predictive power increases with the addition of more features. We
      focus on a predictive context that has been extensively investigated and
      benchmarked in the past-the prediction of protein-protein interactions in yeast.
      We start by using a simple Naive Bayes classifier for integrating diverse sources
      of genomic evidence, ranging from coexpression relationships to similar
      phylogenetic profiles. We expand the number of features considered for prediction
      to 16, significantly more than previous studies. Overall, we observe a small, but
      measurable improvement in prediction performance over previous benchmarks, based
      on four strong features. This allows us to identify new yeast interactions with
      high confidence. It also allows us to quantitatively assess the inter-relations
      amongst different genomic features. It is known that subtle correlations and
      dependencies between features can confound the strength of interaction
      predictions. We investigate this issue in detail through calculating mutual
      information. To our surprise, we find no appreciable statistical dependence
      between the many possible pairs of features. We further explore feature
      dependencies by comparing the performance of our simple Naive Bayes classifier
      with a boosted version of the same classifier, which is fairly resistant to
      feature dependence. We find that boosting does not improve performance,
      indicating that, at least for prediction purposes, our genomic features are
      essentially independent. In summary, by integrating a few (i.e., four) good
      features, we approach the maximal predictive power of current genomic data
      integration; moreover, this limitation does not reflect (potentially removable)
      inter-relationships between the features.

PMID- 15998910
TI  - Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and
      demonstration of the potential to identify severe, moderate, silent, rare, and
      paucimorphic mutations in the general population.
AB  - We have developed a mutation-scanning approach suitable for whole population
      screening for unknown mutations. The method, meltMADGE, combines thermal ramp
      electrophoresis with MADGE to achieve suitable cost efficiency and throughput.
      The sensitivity was tested in blind trials using 54 amplicons representing the
      BRCA1 coding region and a panel of 94 unrelated family breast cancer risk
      consultands previously screened in a clinical diagnostic laboratory. All 10
      common polymorphisms, 15/15 previously identified disease-causing mutations, and
      three previously untested single base changes were identified. Assays of LDLR
      exons 3 and 8 were validated in 460 familial hypercholesteremics and detected 8/9
      known variants. We then applied the exon 3 assay in several DNA banks
      representing approximately 8000 subjects with known cholesterol values and
      applied both assays in one DNA bank (n = 3600). In exon 3 we identified one
      previously reported moderate mutation, P84S (n = 1), also associated with
      moderate hypercholesteremia in this subject; an unreported silent variant, N76N
      (n = 1); and known severe hypercholesteremia splice mutation 313+1G-->A (n = 2).
      Around exon 8 we identified a paucimorphism (n = 35) at the splice site 1061-8T-
      >C (known to be in complete linkage disequilibrium with T705I) and unreported
      sequence variants 1186+11G-->A (n = 1) and D335N G-->A (n = 1). The cholesterol
      value for D335N was on the 96.2 percentile and for T705I, 2/35 carriers were
      above the 99th percentile. Thus, variants with predicted severe, moderate, and no
      effect were identified at the population level. In contrast with case
      collections, CpG mutations predominated. MeltMADGE will enable definition of the
      full population spectrum of rare, paucimorphic, severe, moderate (forme fruste),
      and silent mutations and effects.

PMID- 15998911
TI  - Examples of the complex architecture of the human transcriptome revealed by RACE
      and high-density tiling arrays.
AB  - Recently, we mapped the sites of transcription across approximately 30% of the
      human genome and elucidated the structures of several hundred novel transcripts.
      In this report, we describe a novel combination of techniques including the rapid
      amplification of cDNA ends (RACE) and tiling array technologies that was used to
      further characterize transcripts in the human transcriptome. This technical
      approach allows for several important pieces of information to be gathered about
      each array-detected transcribed region, including strand of origin, start and
      termination positions, and the exonic structures of spliced and unspliced coding
      and noncoding RNAs. In this report, the structures of transcripts from 14
      transcribed loci, representing both known genes and unannotated transcripts taken
      from the several hundred randomly selected unannotated transcripts described in
      our previous work are represented as examples of the complex organization of the
      human transcriptome. As a consequence of this complexity, it is not unusual that
      a single base pair can be part of an intricate network of multiple isoforms of
      overlapping sense and antisense transcripts, the majority of which are
      unannotated. Some of these transcripts follow the canonical splicing rules,
      whereas others combine the exons of different genes or represent other types of
      noncanonical transcripts. These results have important implications concerning
      the correlation of genotypes to phenotypes, the regulation of complex interlaced
      transcriptional patterns, and the definition of a gene.

PMID- 15998912
TI  - Orthologous repeats and mammalian phylogenetic inference.
AB  - Determining phylogenetic relationships between species is a difficult problem,
      and many phylogenetic relationships remain unresolved, even among eutherian
      mammals. Repetitive elements provide excellent markers for phylogenetic analysis,
      because their mode of evolution is predominantly homoplasy-free and
      unidirectional. Historically, phylogenetic studies using repetitive elements have
      relied on biological methods such as PCR analysis, and computational inference is
      limited to a few isolated repeats. Here, we present a novel computational method
      for inferring phylogenetic relationships from partial sequence data using
      orthologous repeats. We apply our method to reconstructing the phylogeny of 28
      mammals, using more than 1000 orthologous repeats obtained from sequence data
      available from the NISC Comparative Sequencing Program. The resulting phylogeny
      has robust bootstrap numbers, and broadly matches results from previous studies
      which were obtained using entirely different data and methods. In addition, we
      shed light on some of the debatable aspects of the phylogeny. With rapid
      expansion of available partial sequence data, computational analysis of
      repetitive elements holds great promise for the future of phylogenetic inference.

PMID- 15998913
TI  - An atlas of human gene expression from massively parallel signature sequencing
      (MPSS).
AB  - We have used massively parallel signature sequencing (MPSS) to sample the
      transcriptomes of 32 normal human tissues to an unprecedented depth, thus
      documenting the patterns of expression of almost 20,000 genes with high
      sensitivity and specificity. The data confirm the widely held belief that
      differences in gene expression between cell and tissue types are largely
      determined by transcripts derived from a limited number of tissue-specific genes,
      rather than by combinations of more promiscuously expressed genes. Expression of
      a little more than half of all known human genes seems to account for both the
      common requirements and the specific functions of the tissues sampled. A
      classification of tissues based on patterns of gene expression largely reproduces
      classifications based on anatomical and biochemical properties. The unbiased
      sampling of the human transcriptome achieved by MPSS supports the idea that most
      human genes have been mapped, if not functionally characterized. This data set
      should prove useful for the identification of tissue-specific genes, for the
      study of global changes induced by pathological conditions, and for the
      definition of a minimal set of genes necessary for basic cell maintenance. The
      data are available on the Web at http://mpss.licr.org and http://sgb.lynxgen.com.

PMID- 15998915
TI  - IOM panel hears concerns about U.S. drug safety system.

PMID- 15998914
TI  - The MicrobesOnline Web site for comparative genomics.
AB  - At present, hundreds of microbial genomes have been sequenced, and hundreds more
      are currently in the pipeline. The Virtual Institute for Microbial Stress and
      Survival has developed a publicly available suite of Web-based comparative
      genomic tools (http://www.microbesonline.org) designed to facilitate multispecies
      comparison among prokaryotes. Highlights of the MicrobesOnline Web site include
      operon and regulon predictions, a multispecies genome browser, a multispecies
      Gene Ontology browser, a comparative KEGG metabolic pathway viewer, a
      Bioinformatics Workbench for in-depth sequence analysis, and Gene Carts that
      allow users to save genes of interest for further study while they browse. In
      addition, we provide an interface for genome annotation, which like all of the
      tools reported here, is freely available to the scientific community.

PMID- 15998916
TI  - Experts take on tuberculosis.

PMID- 15998917
TI  - Oklahoma allows limited medication recycling: program aims to help indigent
      patients.

PMID- 15998918
TI  - Physical therapists' knowledge, attitudes, and professional use of
      nonprescription analgesics.

PMID- 15998919
TI  - The student leadership institute.

PMID- 15998920
TI  - Risks of a nonprescription lovastatin.

PMID- 15998921
TI  - Effects of antimicrobial drug shortages.

PMID- 15998922
TI  - Hazard of compounded anesthetic gel.

PMID- 15998924
TI  - Uncertain times for oral anticoagulation therapy.

PMID- 15998925
TI  - Ximelagatran: an orally active direct thrombin inhibitor.
AB  - PURPOSE: The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage
      and administration, contraindications, and adverse effects of ximelagatran are
      reviewed. SUMMARY: Ximelagatran is the first orally active direct thrombin
      inhibitor to be tested in Phase III clinical trials. After oral administration,
      ximelagatran is rapidly converted to its active metabolite, melagatran.
      Melagatran (after oral ximelagatran administration) predictably inhibits thrombin
      function without need for routine anticoagulation monitoring. Melagatran
      effectively inhibits both free and clot-bound thrombin-a potential
      pharmacodynamic advantage over heparin products. Melagatran has a half-life of
      2.4-4.6 hours, necessitating twice-daily administration. Melagatran is primarily
      eliminated by the kidneys and has not been studied clinically in patients with
      severe renal failure. Ximelagatran has undergone 10 Phase III trials (6 for
      prophylaxis of venous thromboembolism [VTE] due to orthopedic surgery, 1 for
      initial treatment of VTE, 1 for long-term prevention of VTE recurrence, and 2 for
      stroke prophylaxis due to atrial fibrillation). Results were generally positive.
      AstraZeneca applied in December 2003 for marketing approval of ximelagatran for
      prevention of VTE after total knee replacement surgery, long-term prevention of
      VTE recurrence after standard therapy, and stroke prevention due to atrial
      fibrillation. FDA denied approval of ximelagatran for all indications, mainly
      because of increased rates of coronary artery disease events in ximelagatran
      recipients in some studies and the possibility of hepatic failure when the
      medication is used for long-term therapy. CONCLUSION: Ximelagatran has shown
      promise as a possible alternative to warfarin and other anticoagulants but will
      require further study to ensure its safety.

PMID- 15998926
TI  - Association between short-term effectiveness of statins and long-term adherence
      to lipid-lowering therapy.
AB  - PURPOSE: The relationship between low-density lipoprotein (LDL) cholesterol
      reduction in the first 3 months of statin therapy and medication adherence during
      a 33-month follow-up period was studied. METHODS: A retrospective cohort study
      was conducted among enrollees in a Southeastern managed care plan who started
      therapy with atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin
      between October 1999 and August 2001, were enrolled for > or =12 months before
      and > or =6 months after treatment initiation, and had at least one LDL
      cholesterol measurement in the year before and 4-12 weeks after the start of
      therapy. Patients were followed up via electronic pharmacy and medical records
      for up to 33 more months. The follow-up period was divided into 3-month
      intervals; patients were considered adherent if statin therapy was available > or
      =80% of the time. A generalized linear model for repeated measures quantified the
      association between change in LDL cholesterol at 4-12 weeks and medication
      adherence in subsequent intervals, adjusting for demographic, clinical, and
      health-service-use variables. RESULTS: The final sample consisted of 9510
      patients. Medication adherence decreased significantly over time: 59%, 40%, 34%,
      and 21% of patients were adherent at 3, 6, 12, and 36 months, respectively. Mean
      +/- S.D. LDL cholesterol reduction at 12 weeks was 28.9% +/- 19.9%. The relative
      LDL cholesterol reduction at 12 weeks was significantly and independently
      associated with subsequent medication adherence: Compared with subjects in the
      first quartile of LDL cholesterol reduction, those in quartiles 2, 3, and 4 were
      more likely to be adherent in any subsequent interval (adjusted odds ratio [95%
      confidence interval], 1.26 [1.12-1.42], 1.25 [1.11-1.40], and 1.15 [1.02-1.29],
      respectively). Other independent predictors of adherence in months 4-36 included
      adherence during the initial three months of therapy, age, and recent history of
      coronary revascularization. CONCLUSION: Greater reduction in LDL cholesterol
      levels during the first three months of statin therapy was associated with
      greater adherence to lipid-lowering drug therapy.

PMID- 15998927
TI  - Dietary supplement-related adverse events reported to the California Poison
      Control System.
AB  - PURPOSE: Dietary supplement (DS)-related adverse events (AEs) reported to the
      California Poison Control System (CPCS) were studied. METHODS: The CPCS database
      was used to search for all telephone calls from consumers concerning DS-related
      AEs received during the six-month period between April and September 2002. The
      calls were characterized according to the substance involved, the caller's age
      (adult or pediatric), and the type of ingestion (accidental or intentional). Each
      exposure in which symptoms were reported was categorized as involving an AE. Each
      AE was assessed for severity and causality. RESULTS: Data on a total of 1183
      telephone calls were retrieved, of which 828 calls (70%) met the study's
      inclusion criteria. DS exposure occurred in 389 adults (47%) and 438 children
      (53%). DS ingestion was accidental in 360 patients (43%) and intentional in 467
      patients (56%). Exposure resulted in an AE in 480 patients (58%). AEs were
      reported in 353 patients (74%) who ingested products containing ephedra; other
      exposures frequently involved zinc, kava, creatine, and valerian. AEs were
      classified as moderate in 198 patients (41%) who ingested a DS and as severe in
      40 patients (8%). One patient had a fatal reaction. Among the 480 AEs in DS
      exposed consumers, the DS was classified as the definite cause of 1 AE (<1%) and
      a probable cause of 237 (49.4%). The most frequently reported AE symptoms were
      increased heart rate (45%), agitation (30%), vomiting (30%), and nausea (15%).
      CONCLUSION: A majority of DS-related AEs reported by consumers to CPCS involved
      ephedra-containing products.

PMID- 15998928
TI  - Medicare-approved drug discount cards and prescription drug prices.
AB  - PURPOSE: Prescription drug prices with and without the use of Medicare-approved
      drug discount card programs (MADDCs) to purchase medications were studied.
      METHODS: The Medicare.gov Web site was used to determine if the 200 most
      frequently prescribed drugs in the United States in 2003 were covered by a MADDC.
      The lowest and highest MADDC prices at local and mail-order pharmacies and the
      corresponding non-MADDC prices at the same community pharmacies or an Internet
      pharmacy, respectively, were determined. Wilcoxon signed rank tests were used to
      determine if there was a difference between non-MADDC medication prices and MADDC
      prices. RESULTS: Of the top 200 medications prescribed in 2003, 192 (96%) and 189
      (94.5%) were covered by at least one MADDC in a local pharmacy or mail-order
      pharmacy, respectively. Overall, MADDCs saved money compared with purchasing
      medications without a MADDC (p < 0.001). However, a MADDC resulted in a higher
      price than the retail non-MADDC price for 61 (31.8%) of the prescription
      medications at local pharmacies, and using a MADDC at a mail-order pharmacy
      resulted in a higher price than the Internet pharmacy non-MADDC price for 143
      (75.7%) of the drugs. CONCLUSION: MADDC prices for common prescription
      medications were generally lower than prices when MADDCs were not used. The
      highest mail-order MADDC prices were often higher than Internet non-MADDC prices.

PMID- 15998929
TI  - Program for guiding pharmacy students through residency selection.

PMID- 15998930
TI  - Providing homebound patients with pharmaceutical services. Interview.

PMID- 15998931
TI  - Myocardial infarction in an adolescent taking Adderall.

PMID- 15998932
TI  - Practical approach to grading evidence for formulary recommendations.

PMID- 15998933
TI  - ASHP therapeutic position statement on the appropriate use of medications in the
      treatment of attention-deficit/hyperactivity disorder in pediatric patients.

PMID- 15998934
TI  - Clinical pharmacy education in India.

PMID- 15998935
TI  - Peptidyl-Lys metalloendopeptidase-catalyzed 18O labeling for comparative
      proteomics: application to cytokine/lipolysaccharide-treated human retinal
      pigment epithelium cell line.
AB  - We recently proposed a comparative proteomic method utilizing proteolytic 18O
      labeling of peptides catalyzed by peptidyl-Lys metalloendopeptidase (Lys-N) (Rao,
      K. C. S., Carruth, R. T., and Miyagi, M. (2005) Proteolytic 18O labeling by
      peptidyl-Lys metalloendopeptidase for comparative proteomics. J. Proteome Res. 4,
      507-514). Unlike trypsin, which generates a mixture of isotopic isoforms
      resulting from the incorporation of one or two 18O atoms into each peptide
      species, Lys-N incorporates only a single 18O atom into the carboxyl terminus of
      each proteolytically generated peptide in H2(18)O solvent. This study reports the
      first biological application of the Lys-N-based proteolytic 18O labeling method,
      characterizing the proteome changes of cytokine/lipopolysaccharide-treated verses
      untreated human retinal pigment epithelium (ARPE-19) cells. The study resulted
      not only in the identification of 584 proteins but also the determination of the
      relative abundances of 562 proteins in the two proteomes. The results demonstrate
      the usefulness of the Lys-N-based proteolytic 18O labeling method in comparative
      proteomic studies. The results also provide the most comprehensive description of
      the retinal pigment epithelium proteome to date.

PMID- 15998937
TI  - DNA microarrays as salivary diagnostic tools for characterizing the oral cavity's
      microbial community.

PMID- 15998938
TI  - Point detection of pathogens in oral samples.

PMID- 15998939
TI  - The use of soluble, salivary c-erbB-2 for the detection and post-operative follow
      up of breast cancer in women: the results of a five-year translational research
      study.
AB  - A surge of new technological developments, coupled with the limitations of
      existing disease-detection methodologies, is propelling the field of medical
      diagnostics forward at unprecedented rates. Advancements in proteomics and
      nanotechnology are paving the way for diagnostic tests that will be capable of
      rapid multi-analyte detection in both laboratory and non-laboratory settings.
      Technological advancements have also benefited biomarker research to the point
      where saliva is now recognized as an excellent diagnostic medium that can be
      collected simply and non-invasively. Salivary biomarkers have been identified
      that may provide diagnostic information about a variety of cancers and other
      diseases. In particular, proof-of-principle has been demonstrated for salivary c
      erbB-2, whose elevation has been shown to correlate strongly with breast
      malignancy in women. The purpose of this manuscript is to review the past
      literature and present the current research focused on the use of saliva as a
      diagnostic medium for the detection of malignancies that are remote from the oral
      cavity.

PMID- 15998940
TI  - Employment after therapy for localized prostate cancer: widening the perspective.

PMID- 15998941
TI  - Success of bevacizumab trials raises questions for future studies.

PMID- 15998942
TI  - The right equation: mathematicians work to predict tumor growth.

PMID- 15998943
TI  - Central IRBs: why are some institutions reluctant to sign on?

PMID- 15998944
TI  - Stat bite: Tobacco use among U.S. middle and high school students, 2004.

PMID- 15998945
TI  - Hormone replacement therapy for breast cancer survivors: an answered question?

PMID- 15998946
TI  - President's Cancer Panel suggests ways to accelerate cancer treatment
      advancements.

PMID- 15998948
TI  - Employment outcomes of men treated for prostate cancer.
AB  - BACKGROUND: Some organizations recommend prostate cancer screening for men
      younger than age 65 years, many of whom will be employed when they are diagnosed
      and treated for prostate cancer. Yet little is known about how prostate cancer
      and its treatment affect men's employment status. Consequently, we explored
      employment outcomes 6 and 12 months after the diagnosis of prostate cancer.
      METHODS: We collected data from a prospective, population-based, longitudinal
      cohort of 267 men aged 30-65 years who had been diagnosed with prostate cancer
      and compared their likelihood of employment to that of men in two population
      based control groups of 283 and 256 men without prostate cancer. The study
      outcomes were, among all participants, employment status and, among patients with
      prostate cancer, reasons why they remained employed, reasons why their weekly
      hours worked changed, and work-related disabilities. We predicted employment
      using probit regression models. In addition, we tested differences between the
      samples with two-sample Wilcoxon rank sum tests and chi-square tests. All
      statistical tests were two-sided. RESULTS: Patients with prostate cancer were 10
      percentage points (95% confidence interval [CI] = 2.50 to 17.51 percentage
      points; P = .009) less likely to be working 6 months after their diagnosis than
      men without prostate cancer. However, at 12 months after diagnosis, the
      likelihood of employment for prostate cancer patients and control subjects was
      not statistically significantly different (P = .771). Some patients reported that
      cancer and its treatment interfered with their ability to perform physical and
      cognitive tasks at work 12 months after diagnosis. For example, 26% (95% CI =
      18.51% to 33.87%) of men (33 patients) reported that cancer interfered with their
      ability to perform tasks that involved physical effort. CONCLUSIONS: Prostate
      cancer and its treatment appear to have an impact on employment.

PMID- 15998949
TI  - Trends in inflammatory breast carcinoma incidence and survival: the surveillance,
      epidemiology, and end results program at the National Cancer Institute.
AB  - BACKGROUND: Inflammatory breast carcinoma (IBC) appears to be a clinicopathologic
      entity distinct from noninflammatory locally advanced breast cancer (LABC). We
      examined incidence and survival trends for IBC in Surveillance, Epidemiology, and
      End Results (SEER) Program data with a case definition designed to capture many
      of its unique clinical and pathologic characteristics. METHODS: We analyzed
      breast cancer cases diagnosed in the SEER 9 Registries (n = 180,224), between
      1988 and 2000. Breast cancer cases were categorized using SEER's "Extent of
      Disease" codes in combination with International Classification of Diseases for
      Oncology morphology code 8530/3 and classified as IBC (n = 3648), LABC (n =
      3636), and non-T4 breast cancer (n = 172,940). We compared changes in incidence
      rates over 3-year intervals by breast cancer subtype and race using SEER*Stat.
      Survival differences by breast cancer subtype and race were assessed using Kaplan
      Meier curves and log-rank statistics. All statistical tests were two-sided.
      RESULTS: Between 1988 and 1990 and 1997 and 1999, IBC incidence rates (per
      100,000 woman-years) increased from 2.0 to 2.5 (P < .001), whereas those for LABC
      declined (2.5 to 2.0, P = .0025), as did those for non-T4 breast cancer (108 to
      101, P = .0084). IBC incidence rates were statistically significantly higher in
      black women (3.1) than in white women (2.2) during the study period (P < .001).
      Women diagnosed with IBC had statistically significantly poorer survival than
      women with either LABC or non-T4 breast cancer (log-rank test, P < .001). Median
      survival of women with IBC (2.9 years) was statistically significantly shorter
      than that of women with LABC (6.4 years; P < .0001) or non-T4 breast cancer (> 10
      years, P < .0001). Black women with IBC or LABC had poorer survival than white
      women with IBC or LABC, respectively (log-rank test, P < .001). CONCLUSIONS:
      Throughout the 1990s, IBC incidence rose, and survival improved modestly.
      Substantial racial differences were noted in age at diagnosis, age-specific
      incidence rates, and survival outcomes.

PMID- 15998950
TI  - A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs
      and prostate cancer incidence.
AB  - BACKGROUND: Use of aspirin and other nonsteroidal anti-inflammatory drugs
      (NSAIDs) has consistently been associated with a reduced risk of colon cancer.
      Recent epidemiologic studies have suggested that the use of NSAIDs, particularly
      aspirin, may also be associated with a reduced risk of prostate cancer, but the
      evidence remains limited. METHODS: We examined the association between NSAID use
      and prostate cancer incidence among 70 144 men in the American Cancer Society's
      Cancer Prevention Study II Nutrition Cohort. Information on NSAID use was
      obtained from a questionnaire completed at study enrollment in 1992-1993 and was
      updated using follow-up questionnaires in 1997 and 1999. We calculated rate
      ratios (RRs) and 95% confidence intervals (CIs) for prostate cancer incidence
      associated with NSAID use, adjusting for age and potential prostate cancer risk
      factors. RESULTS: During follow-up from 1992-1993 through August 31, 2001, 4853
      cases of incident prostate cancer were identified. Neither current aspirin use
      nor current use of NSAIDs (aspirin and other NSAIDs combined) was associated with
      prostate cancer risk, even at the highest usage level (60 or more pills per
      month). However, long-duration regular use (30 or more pills per month for 5 or
      more years) of NSAIDs was associated with reduced risk of prostate cancer (RR =
      0.82, 95% CI = 0.71 to 0.94). Long-duration regular use of aspirin was also
      associated with reduced risk of prostate cancer (RR = 0.85, 95% CI = 0.73 to
      0.99). The absolute rate of prostate cancer (standardized to the age distribution
      of study participants using 5-year age categories) was 1013 per 100,000 person
      years among men who had never reported NSAID use, and 847 per 100,000 person
      years among long duration regular NSAID users. CONCLUSIONS: These results support
      the hypothesis that long duration regular NSAID use is associated with modestly
      reduced risk of prostate cancer.

PMID- 15998951
TI  - Association of k-ras, b-raf, and p53 status with the treatment effect of
      bevacizumab.
AB  - BACKGROUND: A recent phase III trial showed that the addition of bevacizumab, a
      monoclonal antibody to vascular endothelial growth factor-A, to first-line
      irinotecan, 5-fluorouracil, and leucovorin (IFL) prolonged median survival in
      patients with metastatic colorectal cancer. We carried out a retrospective
      analysis of patients in the trial to evaluate whether mutation status of k-ras, b
      raf, or p53 or P53 expression could predict which patients were more likely to
      respond to bevacizumab. METHODS: Microdissected tumors from 295 patients (274
      primary tumors, 21 metastases) were subject to DNA sequence analysis to identify
      mutations in k-ras, b-raf, and p53. Nuclear P53 expression was determined by
      immunohistochemistry. Hazard ratios and 95% confidence intervals (CI) for overall
      survival were estimated using Cox regression analysis. RESULTS: In all biomarker
      subgroups, estimated hazard ratios for risk of death were less than 1 for
      bevacizumab-treated patients as compared with those for placebo-treated patients.
      Mutations in k-ras and/or b-raf were observed in 88 of 213 patients (41%). Hazard
      ratios for death among patients with tumors with wild-type k-ras/b-raf status, as
      compared with those of patients with mutations in one or both genes, were 0.51
      (95% CI = 0.28 to 0.95) among those treated with IFL plus bevacizumab and 0.66
      (95% CI = 0.37 to 1.18) among those treated with IFL plus placebo. Mutations in
      p53 were found in 139 of 205 patients (68%), and P53 was overexpressed in 191 of
      266 patients (72%); neither p53 mutation nor P53 overexpression was statistically
      significantly associated with survival. CONCLUSIONS: We did not find a
      statistically significant relationship between mutations of k-ras, b-raf, or p53
      and the increase in median survival associated with the addition of bevacizumab
      to IFL in metastatic colorectal cancer.

PMID- 15998952
TI  - Flexible sigmoidoscopy in the PLCO cancer screening trial: results from the
      baseline screening examination of a randomized trial.
AB  - BACKGROUND: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening
      trial is a randomized clinical trial to test the effectiveness of cancer
      screening, including the effect of flexible sigmoidoscopy screening on colorectal
      cancer mortality. Here we report findings from the baseline screening flexible
      sigmoidoscopy examination. METHODS: Analyses included 77,465 men and women aged
      55-74 years who were enrolled at 10 screening centers. The trial administered
      baseline risk factor questionnaires, offered 60-cm flexible sigmoidoscopy
      examinations, referred patients with screen-detected colorectal polyps or masses
      to personal physicians, and tracked subjects with polyps or masses to determine
      results from diagnostic follow-up. Cochran-Mantel-Haenszel statistics and
      logistic regression were used to test for differences in proportions according to
      sex and age. RESULTS: A total of 64 658 subjects (83.5%) underwent screening
      flexible sigmoidoscopy, and at least one polyp or mass was identified in 15,150
      subjects (23.4%). Of these, 74.2% received follow-up lower endoscopic procedures.
      Follow-up lower endoscopy was more frequent in subjects with at least one larger
      (> or = 0.5 cm) polyp or mass (86.0% [95% confidence interval {CI} = 84.6% to
      87.4%] and 81.0% [95% CI = 79.8% to 82.2%] in women and men, respectively) than
      in those with a smaller (< 0.5 cm) polyp or mass (69.1% [95% CI = 67.5% to 70.6%]
      and 65.4% [95% CI = 64.1% to 66.7%] in women and men, respectively). The yields
      per 1000 screened, depending on 5-year age group, were as follows: for colorectal
      cancer, 1.1-2.5 in women and 2.4-5.6 in men; for advanced adenoma, 18.0-30.4 in
      women and 36.1-49.1 in men; and for colorectal cancer or any adenoma, 50.6-79.6
      in women and 101.9-128.6 in men. Approximately 77% (130/169) of the colorectal
      adenocarcinoma patients were stage I or II at diagnosis. CONCLUSIONS: Acceptance
      of screening flexible sigmoidoscopy was high. Diagnostic follow-up varied
      according to polyp size, yet cancer or adenoma detection rates met expectations.

PMID- 15998953
TI  - MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean
      population.
AB  - BACKGROUND: Melanoma risk factors include fair pigmentation, multiple nevi, low
      DNA repair capacity, and CDKN2A or CDK4 mutations. Variants of the melanocortin-1
      receptor (MC1R) gene have been associated with fair pigmentation and melanoma
      risk, and a polymorphism of the Agouti Signaling Protein (ASIP) gene has been
      associated with dark pigmentation. We examined MC1R and ASIP genotypes in
      relation to phenotypic characteristics, sporadic and familial melanoma risk, and
      melanoma thickness as an indicator of disease progression in a Mediterranean
      population. METHODS: We studied 267 melanoma patients and 382 control subjects
      from a case-control study and a family study in northeastern Italy. Host factors
      were assessed by physical examination, questionnaire, spectrophotometer, and
      minimal erythema dose measurement. MC1R was sequenced, ASIP was genotyped, and
      DNA repair capacity was measured by the host-cell reactivation assay. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression
      models. Effect modification of the association between MC1R and melanoma risk by
      phenotypic characteristics and DNA repair capacity was also assessed. All
      statistical tests were two-sided. RESULTS: Carrying MC1R variant alleles was
      associated with a two- to fourfold increase in risk of both sporadic and familial
      melanoma compared with carrying wild-type MC1R, particularly in individuals
      carrying multiple variant alleles (OR = 3.9; 95% CI = 3.3 to 4.6). This
      association was stronger in individuals with fewer additional risk factors (those
      with dark skin or few nevi). MC1R variant allele carriers were also three to four
      times more likely than were non-carriers to have thick melanomas. The ASIP
      polymorphism was not associated with pigmentation, nevi, or melanoma risk.
      CONCLUSIONS: MC1R was associated with melanoma risk and progression in a
      Mediterranean population, particularly in the absence of other strong risk
      factors, such as freckling or many nevi.

PMID- 15998954
TI  - Human herpesvirus 8 DNA in serum during seroconversion in allogeneic bone marrow
      transplant recipients.
AB  - To determine the prevalence of human herpesvirus 8 (HHV-8) infection, the rate of
      HHV-8 seroconversion, and the presence of serum HHV-8 DNA after bone marrow
      transplantation (BMT), we evaluated sera from 187 Italian BMT donor-recipient
      pairs. Antibodies to lytic and latent HHV-8 antigens were detected by
      immunofluorescence. Sera of donor-recipient pairs who seroconverted were examined
      by real-time polymerase chain reaction (RT-PCR). Before BMT, 24 (13%) of 187
      donors and 20 (11%) of 187 recipients were seropositive; after BMT, 28 (15%) of
      187 recipients were seropositive. Seroconversion occurred in 19 (11%) of 167
      recipients seronegative at baseline: 14 (9%) from 149 seronegative donors and
      five (28%) from 18 seropositive donors (relative risk of seroconversion with BMT
      from a seropositive donor = 2.96, 95% confidence interval = 1.21 to 7.25; P =
      .02, two-sided Fisher's exact test). One donor and two recipients who
      seroconverted after BMT were positive for HHV-8 by RT-PCR. No HHV-8-related
      complications were observed after a median follow-up of 6 years. BMT-associated
      HHV-8 seroconversion is relatively common in seronegative recipients from
      seropositive donor, but factors other than BMT may also contribute to
      seroconversion.

PMID- 15998955
TI  - Re: Association of a common variant of the CASP8 gene with reduced risk of breast
      cancer.

PMID- 15998956
TI  - Re: The role of overdiagnosis and reclassification in the marked increase of
      esophageal adenocarcinoma incidence.

PMID- 15998957
TI  - Use of physician profiles to influence prescribing of topical corticosteroids.
AB  - BACKGROUND: Physician profiling is a tool used to attempt to affect changes in
      prescribing. The Drug Evaluation Alliance of Nova Scotia (DEANS) decided to
      implement a physician profiling project to determine if prescribing of topical
      corticosteroids could be altered. OBJECTIVES: To evaluate a DEANS initiative
      utilizing physician prescribing profiles to shift prescribing of topical
      corticosteroids from higher to lower potency agents in beneficiaries of the Nova
      Scotia Seniors' Pharmacare Program. METHODS: Administrative claims from the Nova
      Scotia Seniors' Pharmacare program were used to identify prescriptions for
      topical corticosteroids. Prescriptions were summarized at the individual
      physician level, and aggregated by Anatomical Therapeutic Classification into
      weak, moderately potent, potent and very potent products. The number of
      prescriptions for topical corticosteroids was compared for the twelve-month
      period before and after mailing of the profiles. Overall results were aggregated
      by utilization and expenditures. RESULTS: The number of prescriptions for topical
      corticosteroids per physician profiled was 44.0 in 2000/2001 and 42.8 in
      2001/2002 (p = NS) and the expenditures per physician profiled were 838.94
      dollars in 2000/2001 and 826.81 dollars in 2001/2002 (p = NS). There was a small
      decrease in prescriptions dispensed for potent topical products over the
      profiling period (52.4% of prescriptions in 2000/2001 versus 51.5% of
      prescriptions in 2001/2002, p=0.03). Otherwise, changes in utilization or
      expenditures for topical corticosteroids were not statistically different between
      the profiling periods. CONCLUSIONS: This project showed that mailing unsolicited
      individual-level profiles did not alter prescribing or expenditures for topical
      corticosteroids over a two-year period. Further work is needed to determine
      physician attitudes towards such projects.

PMID- 15998958
TI  - No one asked the baby -- an ethical issue in placebo-controlled trials in
      pregnant smokers.
AB  - This case report involving a placebo-controlled nicotine patch trial illustrates
      the difficult issue of conducting placebo studies in pregnancy, when one of the
      two patients involved cannot be asked to consent.

PMID- 15998959
TI  - Utilization of non-steroidal anti-inflammatory drugs in Quebec: adherence to the
      Canadian consensus on prescription guidelines.
AB  - BACKGROUND: Adverse events associated with the use of non-steroidal anti
      inflammatory drugs (NSAIDs) have led to the publication of Canadian prescription
      guidelines. Prescription practices following the publication of these guidelines
      and the introduction of COX-2 inhibitors in the Quebec formulary of reimbursed
      medications remain largely unexplored. OBJECTIVES: To compare the prevalence of
      contra-indications and selected risk factors for NSAID-toxicity among COX-2
      inhibitor users and non-selective NSAID users. METHODS: A case-control analysis
      was conducted in a random sample of Quebec adult drug plan members who were
      treated with celecoxib (n=42,422 cases), rofecoxib (n=25,674 cases), full-dose
      (anti-inflammatory doses) of non-selective NSAIDs (n=9,673 cases), or low-dose
      NSAIDs (n=2,745 controls) in the year 2000. Data were obtained from the Quebec
      prescription and medical services databases (RAMQ). RESULTS: Patients with a
      history of gastropathy were more likely to be prescribed COX-2 inhibitors than
      low-dose NSAIDs; the odds ratios were 1.73 (95%CI: 1.56-1.91) and 1.49 (1.33
      1.66), respectively for celecoxib and rofecoxib. Corresponding results for
      concomitant use of anticoagulants were 1.95 (1.34-2.83) for celecoxib and 1.87
      (1.26-2.77) for rofecoxib, and for use of corticosteroids they were 1.29 (1.08
      1.54) and 1.23 (1.01-1.49). Conversely, patients with the following
      characteristics were less likely to receive COX-2 inhibitors than low-dose non
      selective NSAIDs: age 75+ (OR=0.64; 0.56-0.72 for celecoxib, OR=0.48; 0.76-0.99
      for rofecoxib), hypertension (OR=0.83; 0.75-0.92 for celecoxib, OR=0.87; 0.77
      0.97 for rofecoxib), and concomitant use of diuretics (OR=0.72; 0.63-0.82 for
      celecoxib; OR=0.77; 0.66-0.89 for rofecoxib). CONCLUSION: Patients with risk
      factors for NSAID gastropathy were more likely prescribed COX-2 inhibitors, while
      the presence of other contra-indications led to the prescription of low-dose non
      selective NSAIDs. However, 12.7% of users of full-dose non-selective NSAIDs were
      age 75+ and 12.0% had a history of gastropathy, which are considered important
      risk factors for adverse events.

PMID- 15998960
TI  - Effectiveness and cost-effectiveness of antibiotic treatments for community
      acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB).
AB  - BACKGROUND: The antibacterial activity, tolerability profile and duration of
      treatment associated with antibiotics are important therapy attributes when
      considering treating patients for lower respiratory tract infections (LRTIs),
      such as community acquired pneumonia (CAP) and acute exacerbations of chronic
      bronchitis (AECB). OBJECTIVES: To investigate the effectiveness and cost
      effectiveness of oral antibiotics used in the treatment of LRTIs. METHODS: A
      cohort of inhaled corticosteroids users who were diagnosed with a LRTI and
      dispensed a prescription for one of the antibiotics under study on the same day
      as the diagnosis was selected from the administrative health databases of the
      Regie de l'assurance maladie du Quebec (RAMQ). The risks of treatment failure
      were estimated using a logistic regression analysis. Treatment failure was
      defined as another prescription for any antibiotic, an emergency room visit or
      hospitalization for LRTIs, or death, in the 20 days following the dispensation of
      the first antibiotic prescribed. A cost-minimization analysis was performed in
      which only the drug costs related to the first antibiotic filled were considered.
      RESULTS: A total of 3,610 episodes of LRTIs were studied. There were no
      significant differences between antibiotics in terms of their respective adjusted
      odds ratios for rates of failure. However, the lower cost associated with
      azithromycin was significantly different from the costs associated with any other
      antibiotic (p<0.0001). CONCLUSION: Clinical effectiveness appears to be similar
      amongst second line antibiotics that are commonly used in the treatment of LRTIs
      in the community. Using a cost-minimization analysis, azithromycin appears to be
      the most cost-effective antibiotic treatment in this setting.

PMID- 15998961
TI  - Purification of primary malignant B-cells and immunoblot analysis of bcl-2 family
      proteins.
AB  - The ability to isolate relatively pure populations of primary normal and
      malignant lymphocytes has brought studies of lymphoid malignancies to the
      forefront of cancer research. Apoptosis (programmed cell death) plays a key role
      in controlling normal B-cell numbers, and resistance to apoptosis contributes to
      lymphomagenesis and reduces the effectiveness of chemotherapy and radiotherapy.
      Multiple Bcl-2 family proteins orchestrate key life and death decisions in
      lymphocytes, and the prototypical family member, Bcl-2, is activated by
      reciprocal translocation in human lymphoma. Here, we describe an immunomagnetic
      method to isolate and purify malignant B-cells suitable for in vitro analyses
      from lymph node biopsies. Methods to analyze the expression of Bcl-2 family
      proteins by immunoblotting also are described.

PMID- 15998963
TI  - Demonstration of a germinal center immunophenotype in lymphomas by
      immunocytochemistry and flow cytometry.
AB  - The germinal center plays an important role in the pathogenesis of B-cell
      lymphomas, and evidence exists to suggest that most cases are germinal center or
      postgerminal center derived. Burkitt lymphoma and follicular lymphoma are derived
      from the germinal center stage of differentiation. It has been shown that diffuse
      large B-cell lymphomas with a germinal center-type pattern of RNA expression or a
      germinal center cell phenotype using immunocytochemistry have a more favorable
      outcome compared with those with a postgerminal center/activated profile.
      Microarray technology may not be available in many diagnostic laboratories, and
      antibody-based methods are much simpler and cheaper and are therefore more
      applicable to the routine setting. Immunocytochemistry has the advantage that the
      cells of interest are identified morphologically, and it is applicable
      retrospectively to fixed tissue. The main disadvantage is that only single-color
      staining is currently used in the routine setting. Flow cytometry allows one to
      obtain a more precise definition of individual cell types. The cells of interest
      are identified by a combination of physical characteristics and by the use of
      multiple antibodies labeled with different fluorochromes. Flow cytometry has the
      major advantage of being able to analyze very large numbers of cells, and results
      can be obtained within a few hours of the specimen being taken. The methods
      described allow B-cell lymphomas to be crudely divided into two groups, those
      with a germinal center phenotype and those that are mainly postgerminal center
      tumors. As knowledge of the normal biology of the germinal center develops, it
      will become possible to use immunophenotypic methods to more precisely classify
      all types of mature B-cell malignancies.

PMID- 15998962
TI  - Molecular diagnosis of lymphoma: outcome prediction by gene expression profiling
      in diffuse large B-cell lymphoma.
AB  - This chapter describes the illness diffuse large B-cell lymphoma (DLBCL) and why
      research has and continues to focus on creating accurate predictors of response
      to treatment to allow individual risk assessment for a patient and
      individualization of treatment choice to maximize the chances of cure. Microarray
      technology has the promise to bring these objectives within reach. The first
      papers attempting to identify molecular signatures of response and outcome using
      microarray technology were generated using DLBCL samples and are described. The
      different types of microarray platform and data analysis tools are reviewed
      followed by a detailed step-by-step guide to data generation using the Affymetrix
      chip system from RNA extraction to laser scanning of the hybridized and stained
      chips.

PMID- 15998964
TI  - Karyotyping lymph node biopsies in non-Hodgkin's lymphoma.
AB  - Culture and transport methods are described that allow chromosomes to be obtained
      from lymph node biopsies with a high success rate, even when the biopsy is taken
      at a distant site from the cytogenetic laboratory. Optimal banding techniques for
      the identification of these chromosomes are given, along with hints on how to
      correct any problems encountered on initial staining. We also describe how to
      prepare this material for fluorescence in situ hybridization techniques, both for
      further delineation of complex chromosomal rearrangements and for interphase
      analysis in cases in which conventional cytogenetics has not been successful.

PMID- 15998965
TI  - Identification of lymphoma-associated antigens using SEREX.
AB  - Serological analysis of recombinant complementary deoxyribonucleic acid (cDNA)
      expression libraries (SEREX) is a powerful approach to identify immunogenic
      cancer-associated proteins using antibodies that are naturally present in the
      serum of cancer patients. This technique involves the screening of a relevant
      cDNA expression library with patient serum that has been cleaned to remove any
      antibodies that may recognize bacterial and/or viral proteins. Once antigens have
      been identified and their reactivity has been confirmed with a second round of
      screening, the gene encoding the protein can be sequenced and identified.
      Antigens can then be screened with a panel of allogenic sera from other patients
      and control individuals. This identifies disease-specific antigens, which may be
      useful diagnostic markers or, alternatively, targets for immunotherapy. This
      chapter describes the SEREX methodology in full.

PMID- 15998966
TI  - Determining mutational status of immunoglobulin v genes in chronic lymphocytic
      leukemia: a useful prognostic indicator.
AB  - Determining the clonal origins of malignant B-cells will have an impact on
      disease understanding and management. In this regard, immunoglobulin variable (V)
      region gene analysis already is having a significant impact in delineating the
      tumor cell of origin. It can identify, among other features whether such a cell
      has undergone somatic mutation, which usually occurs within germinal centres.
      Remarkably, in chronic lymphocytic leukemia (CLL), the mutational status of V
      genes has allowed researchers to identify two subsets of disease, one originating
      from an unmutated B-cell with a markedly poorer disease outcome and the other
      from a mutated B-cell, which associates with long-term survival. The V gene
      status in CLL thus provides a robust indicator of disease outcome, which is
      beginning to shape clinical treatment. This chapter describes in detail the
      methodology for determining V gene usage in CLL, from acquisition of patient
      sample to generating the V-gene readout.

PMID- 15998967
TI  - Idiotype gene rescue in follicular lymphoma.
AB  - Beyond the morphological, immunophenotypic, and genetic information used for the
      diagnosis of lymphoid malignancies, molecular analyses have deepened our insights
      into the development of B-cell lymphomas. We have learned that B-cell tumors can
      be grouped according to the mutational status of their immunoglobulin variable
      (V) region genes, and this has become an important prognostic tool in chronic
      lymphocytic leukemia. The analysis of V genes also has allowed us to more
      precisely place B-cell lymphomas relative to their normal B-cell counterparts and
      to the germinal center where somatic hypermutation takes place. It has become
      evident that many of the common B-cell tumors arise at this site and are able to
      respond to stimuli, which govern normal B-cells. In this chapter, we focus on the
      analysis of V genes in follicular lymphomas based on the experience in our
      laboratory and provide a detailed guide for this analysis.

PMID- 15998968
TI  - Immunoglobulin gene mutation patterns and heterogeneity of marginal zone
      lymphoma.
AB  - Marginal zone (MZ) or MZ-like B-cells "home" outside the follicles of peripheral
      lymphoid tissues. Prototypic examples of these B-cells are those that home the MZ
      of the spleen, although B-cells with similar phenotypic and functional features
      can be found in the subepithelial (SE) areas of tonsil, in the Peyer's patches,
      in the lymph nodes, and in the thymic medulla. MZ-like B-cells also develop in
      mucosa-associated lymphoid tissue (MALT) and other sites (salivary glands,
      thyroid) that acquire organized lymphoid tissue after chronic antigenic
      stimulation, such as Hp infection in gastric maltomas or autoimmune insult in
      Sjogren's syndrome. Beside the so-called extranodal B-cell MALT lymphoma, the
      splenic MZ lymphoma with or without circulating villous lymphocytes and
      monocytoid lymphoma also are thought to originate from MZ B-cells. Normal MZ-like
      B-cells can be isolated from different tissue sources (tonsil, spleen) by using
      combination Percoll gradients, magnetic fractionation, and fluorescence-activated
      cell sorting. Analyses of morphology, phenotype, and functions of these purified
      MZ B-cells demonstrated that in humans, MZ B-cells are rather heterogeneous,
      comprising virgin and memory B-cells and of cells specialized in different types
      of human responses. In this chapter, we review the main procedures used to
      isolate and test the phenotypic and functional features of the MZ B-cells from
      human tonsil and spleen in our laboratory and discuss their characteristics by
      comparing them with the MZ B-cell-derived lymphomas.

PMID- 15998969
TI  - T-cell receptor molecular diagnosis of T-cell lymphoma.
AB  - Malignant and reactive lymphoproliferations in most cases can be distinguished by
      histology and immunohistology alone; however, in T-cell lymphoproliferations and
      lymphoproliferations of unknown origin, histology often is inconclusive, and
      there is no reliable protein marker of malignancy. At the genomic level T-cell
      neoplasms clonally rearrange T-cell receptor (TCR) genes that can serve as clonal
      markers. In comparison with Southern blot analysis, polymerase chain reaction
      (PCR) techniques increasingly are being used to detect these rearrangements
      because PCRs are rapid, easy to perform, and can be used to amplify poor-quality
      deoxyribonucleic acid (DNA) from paraffin-embedded formalin-fixed biopsies.
      Nevertheless there are a number of problems associated with the detection of gene
      rearrangements using PCR. The foremost of these is improper primer annealing that
      will lead to false-negative or false-positive PCR results that may arise from
      poor primer design, especially for TCRB genes with an extensive variable (V),
      diversity (D), and joined (J) gene repertoire. There also can be difficulty in
      discriminating between clonal and polyclonal PCR products unless specific methods
      such as heteroduplex analysis or gene scanning are used. In this chapter, we
      describe methods, derived from a recent European collaborative BIOMED-2 program,
      for the detection of TCRG, B, and D rearrangements. TCRB VJ and DJ gene
      rearrangements are detected using 23 VB primers, 13 JB primers, and 2 DB primers
      in 3 multiplex tubes. TCRG VJ gene rearrangements are detected with four VG and
      two JG primers in two multiplex tubes, and TCRD VJ, VD, DJ, and DD rearrangements
      are detected with six VD primers, four JD primers, and two DD primers in one
      multiplex tube. Gaussian distributions of polyclonal PCR products are seen at
      specific size ranges for both TCRB and TCRG. Interpretation of TCRD
      rearrangements is more complex because of the wide range in PCR product size and
      often low numbers of TCRGD cells in target tissue. For all loci, some indication
      of gene usage can be ascertained by labeling the primers with different
      fluorochromes and gene scan analysis of PCR products. Furthermore the
      complementarity of the TCR loci affords an unprecedented high clonal detection
      rate. In addition, we also describe a set of control gene primers designed to
      amplify amplicons of 100, 200, 300, 400, and 600 bp for the assessment of the
      integrity and amplifiability of DNA.

PMID- 15998970
TI  - Cloning of immunoglobulin chromosomal translocations by long-distance inverse
      polymerase chain reaction.
AB  - Many subtypes of B-cell malignancy are characterized by chromosomal
      translocations that target the immunoglobulin loci. Molecular cloning of such
      translocations continues to allow the identification of genes whose deregulated
      expression plays a pivotal role in the pathogenesis of B-cell malignancy. The
      clustering of breakpoints within the immunoglobulin loci has allowed the
      development of rapid and robust polymerase chain reaction methods for cloning. We
      discuss in this chapter the use of long-distance inverse polymerase chain
      reaction methods to clone immunoglobulin chromosomal translocation breakpoints
      from clinical material. These methods have been successfully applied to several
      other types of chromosomal translocation including those involving other genes
      such as BCL6, ETV6, and MYC.

PMID- 15998971
TI  - Sequential fluorescence in situ hybridization analysis for trisomy 12 in B-cell
      chronic lymphocytic leukemia.
AB  - Tumor-specific chromosomal abnormalities are attracting a large interest owing to
      the diagnostic, prognostic, and therapeutic importance. The development of
      molecular techniques, e.g., fluorescence in situ hybridization (FISH), have
      improved the detection of specific chromosomal abnormalities in chronic
      lymphocytic leukemic (CLL). By using FISH, the problem with tumor cells with low
      mitotic rate is avoided since this method readily detects clonal aberrations also
      in nondividing, interphase cells. Three different types of probes are used: (1)
      centromeric probes for numerical chromosome abnormalities, (2) whole chromosome
      paints, and (3) locus-specific probes. The DNA probes are labeled with
      fluorochromes and the signals yielded are strong enough to enable analysis of
      interphase cells. These DNA probes may be directed towards any defined
      chromosomal region and this chapter will in detail describe the FISH method as a
      detector of trisomy 12 in CLL.

PMID- 15998972
TI  - Splenic marginal zone lymphoma: 7q abnormalities.
AB  - 7q abnormalities are the most common cytogenetic or genetic aberrations found in
      splenic marginal zone lymphoma. The molecular methods whereby these regions of
      genetic loss can be characterized are discussed in this chapter. Emphasis is
      given to careful experimental design, for example sample purification and
      optimization, that is, ensuring that only target sequences are amplified. There
      also is discussion of result interpretation, pitfalls that may be encountered,
      and alternative visualization techniques that might be used.

PMID- 15998973
TI  - BCL-6: rearrangement and mutation in lymphoma.
AB  - BCL-6 is a zinc finger transcription factor that is highly expressed in normal
      germinal center B-cells. Its function is to prevent differentiation and apoptosis
      and allow growth. BCL-6 also is expressed in various lymphoproliferative
      conditions, for example, diffuse large cell lymphoma, Burkitt's lymphoma, and
      follicular lymphoma as well as lymphocyte predominant Hodgkin's disease.
      Expression also has been demonstrated in some T-cell lymphomas. In diffuse large
      cell lymphoma, BCL-6 is involved in translocations with a number of different
      translocation partners but most commonly the immunoglobulin heavy chain locus.
      The first intron of BCL-6 is heavily mutated, and detailed analysis reveals two
      "hotspots." The mutated region appears to be within a transcriptional control
      region, and there is the potential for alterations to contribute to
      overexpression of BCL-6. Methods for deoxyribonucleic acid extraction from
      lymphoma samples and amplification by polymerase chain reaction of the
      hypermutated intronic region are described.

PMID- 15998974
TI  - Antibody techniques used in the study of anaplastic lymphoma kinase-positive
      ALCL.
AB  - Antibodies enable relatively simple, rapid, and reproducible studies to be
      performed on protein expression in both normal and neoplastic cells. The
      availability of suitable reagents for routine diagnostic use has revolutionized
      the study of leukemia and lymphoma pathology. The use of antibodies specific for
      anaplastic lymphoma kinase (ALK) protein has permitted the identification of the
      tumor entity ALK-positive from the poorly defined morphological category of
      anaplastic large cell lymphoma. Antibody techniques have also provided major new
      insights into the biology of these tumors. This chapter describes the use of
      antibodies in both immunolabeling (immunocytochemical and immunofluorescence)
      procedures and in biochemical procedures in the study of ALK-positive ALCL.

PMID- 15998975
TI  - Identification of anaplastic lymphoma kinase variant translocations using 5'RACE.
AB  - Anaplastic lymphoma kinase (ALK) is abnormally expressed in anaplastic large cell
      lymphoma (ALCL) and its expression associated with chromosomal translocations
      involving the ALK gene at 2p23. These translocations lead to the synthesis of
      novel chimeric proteins that retain the C-terminal portion of ALK, where the
      tyrosine kinase domain is located. In most of these tumors, the t(2;5)(p23;q35)
      translocation causes fusion of the ALK gene to the 5' region of the nucleophosmin
      (NPM) gene, but other different ALK partners have been identified, including
      nonmuscle tropomyosin (TPM3), TRK-fused gene (TFG), 5' aminoimidazole-4
      carboxamide ribonucleotide formyltranferase/IMP cyclohydrolase (ATIC), clathrin
      heavy chain gene (CLTC), and moesin (MSN). The characterization of these ALK
      partners has been performed using different molecular methods, including the 5'
      Rapid Amplification of complementary deoxyribonucleic acid (cDNA) Ends (5'RACE)
      polymerase chain reaction (PCR)-based technique. This approach allows the
      potential amplification and identification of either 5' or 3' mRNA ends from an
      internal known sequence. In ALK translocations, identification of the 5' gene
      involved has been performed using primers designed within the known 3' catalytic
      domain of the ALK. Initial reaction consists in a first-strand cDNA synthesis
      primed using a gene-specific antisense primer (ALK1), performing the cDNA
      conversion of specific messenger ribonucleic acids, and maximizing the potential
      for complete extension to the 5'-end of the message. After cDNA synthesis, the
      first-strand product is purified from unincorporated dNTPs and ALK1. Terminal
      deoxynucleotidyl transferase is used to add homopolymeric tails to the 3' ends of
      the cDNA. Tailed cDNA is then amplified by PCR using a nested gene-specific
      primer (ALK2), which anneals 3' to ALK1, and a complementary homopolymer
      containing an anchor primer (i.e., AAP), which permits amplification from the
      homopolymeric tail. This allows amplification of unknown sequences between the
      ALK2 and the 5' end of the mRNA. Further, nested PCRs usually are required to
      confer an adequate level of specificity to the process to permit the
      characterization of RACE products. The reamplification is achieved by using a
      nested gene-specific primer (ALK3), which anneals 3' to ALK2, and a universal
      amplification primer, which anneals to the 5' sequence previously introduced by
      the AAP primer.

PMID- 15998976
TI  - Follicular lymphoma: quantitation of minimal residual disease by PCR of the
      t(14;18) translocation.
AB  - During the past decade, considerable advances have been made in the sensitivity
      of detection of residual lymphoma and leukemia cells. In particular, polymerase
      chain reaction (PCR)-based assays are capable of detecting one tumor cell in as
      many as 106 normal cells. The applicability of these techniques has been made
      possible by the identification and cloning of the breakpoints associated with
      specific chromosomal translocations associated with particular subtypes of
      lymphoma, best studied for the t(14;18), which occurs in most cases of follicular
      lymphoma. Although we are approaching the time when PCR-based methods of
      detection of minimal residual lymphoma detection become a routine part of
      staging, both at diagnosis and after therapy, it is not yet possible to determine
      whether the detection of residual lymphoma cells by PCR is an indication to
      continue therapy. Therefore, although these techniques provide a useful adjunct
      to standard methods of detection and diagnosis, their role in staging of disease
      outcome remains investigational.

PMID- 15998978
TI  - Attaching unit costs to Australia's National Survey of Mental Health and
      Wellbeing.
AB  - BACKGROUND: In mental health, policy-makers and planners are increasingly being
      asked to set priorities. This means that health economists, health services
      researchers and clinical investigators are being called upon to work together to
      define and measure costs. Typically, these researchers take available service
      utilisation data and convert them to costs, using a range of assumptions. There
      are inefficiencies, as individual groups of researchers frequently repeat
      essentially similar exercises in achieving this end. There are clearly areas
      where shared or common investment in the development of statistical software
      syntax, analytical frameworks and other resources could maximise the use of data.
      AIMS OF THE STUDY: This paper reports on an Australian project in which we
      calculated unit costs for mental health admissions and community encounters. In
      reporting on these calculations, our purpose is to make the data and the
      resources associated with them publicly available to researchers interested in
      conducting economic analyses, and allow them to copy, distribute and modify them,
      providing that all copies and modifications are available under the same terms
      and conditions (i.e., in accordance with the 'Copyleft' principle). Within this
      context, the objectives of the paper are to: (i) introduce the 'Copyleft'
      principle; (ii) provide an overview of the methodology we employed to derive the
      unit costs; (iii) present the unit costs themselves; and (iv) examine the total
      and mean costs for a range of single and comorbid conditions, as an example of
      the kind of question that the unit cost data can be used to address. METHOD: We
      took relevant data from the Australian National Survey of Mental Health and
      Wellbeing (NSMHWB), and developed a set of unit costs for inpatient and community
      encounters. We then examined total and mean costs for a range of single and
      comorbid conditions. RESULTS: We present the unit costs for mental health
      admissions and mental health community contacts. Our example, which explored the
      association between comorbidity and total and mean costs, suggested that
      comorbidly occurring conditions cost more than conditions which occur on their
      own. DISCUSSION: Our unit costs, and the materials associated with them, have
      been published in a freely available form governed by a provision termed
      'Copyleft'. They provide a valuable resource for researchers wanting to explore
      economic questions in mental health. IMPLICATIONS FOR HEALTH POLICIES: Our unit
      costs provide an important resource to inform economic debate in mental health in
      Australia, particularly in the area of priority-setting. In the past, such debate
      has largely been based on opinion. Our unit costs provide the underpinning to
      strengthen the evidence-base of this debate. IMPLICATIONS FOR FURTHER RESEARCH:
      We would encourage other Australian researchers to make use of our unit costs in
      order to foster comparability across studies. We would also encourage Australian
      and international researchers to adopt the 'Copyleft' principle in equivalent
      circumstances. Furthermore, we suggest that the provision of 'Copyleft'
      contingent funding to support the development of enabling resources for
      researchers should be considered in the planning of future large-scale
      collaborative survey work, both in Australia and overseas.

PMID- 15998979
TI  - Using willingness to pay to measure family members' preferences in mental health.
AB  - BACKGROUND: Willingness to pay is a valuation technique that has rarely been
      applied in mental health economics. First used in environmental economics to
      measure the intangible value of environmental improvements, WTP has increasingly
      been used in health care economics. The technique may be useful in mental health
      policy research where it can be critical to include the intangible impact of
      mental health treatment on individuals other than the person with illness, such
      as family members, in cost-benefit analyses. AIMS OF THE STUDY: The goal of the
      study was to test the application of WTP in a sample of individuals who have
      family members with serious mental illness. This paper describes the survey
      development process and the feasibility analysis that was conducted as part of
      the study. METHODS: A mail survey was designed by the author in two phases and
      utilized cognitive pretests and focus group pretests in the process of
      development. Qualitative analysis of this process resulted in a revised survey
      instrument that was then distributed to a random sample of 2000 individuals who
      have family members with mental illness. Feasibility was evaluated based upon the
      study response rate, the willingness to pay item response rate and an outlier
      response analysis. RESULTS: Qualitative analysis during the survey development
      process found that it was critical to consider two areas of concern in the
      application of WTP with this population in the mental health field. Some
      respondents experienced a highly emotional response to the initial versions of
      the survey, and complex probabilities were difficult for the respondents to
      answer. These findings resulted in significant modifications in the survey
      design. The analysis of response rate, WTP item non-response rate, and outlier
      responses found no significant concerns regarding overall feasibility of WTP with
      this population. DISCUSSION: Based upon the results from this study, WTP is a
      potentially useful tool for further research in the mental health policy and
      economics field. However, significant accommodations must be made in survey
      design to account for a possibility of a high level of emotional distress for
      those dealing with the illness of a family member. Some of these modifications
      may be in contrast to the recommendations currently being followed in health care
      economics. Face-to-face surveys may be preferred in some cases, such as with
      elderly respondents. Limitations of this study include the lack of targeted
      follow-up due to the anonymous study design and the fact that there are so few
      models for WTP studies in mental health. IMPLICATIONS FOR MENTAL HEALTH POLICY:
      Given that effective mental health programs can be matched with additional
      expenditures, it is important to explore comprehensive measures of value for
      treatment in cost-benefit analysis. The values of persons whose family members
      have serious mental illness are important to consider in setting policy. The
      success of this study suggests that WTP could be used in other settings, e.g., to
      understand community preferences for mental health treatment programs, to
      understand differences in preferences across multiple stakeholder groups.

PMID- 15998980
TI  - Effects of antipsychotic medication on psychiatric service utilization and cost.
AB  - BACKGROUND: Based on randomized clinical trials, consensus has been emerging that
      the first line of treatment for individuals with psychotic disorders should be
      the newer atypical or second generation antipsychotic medications rather than the
      older neuroleptics. Given that acquisition costs of atypical antipsychotics are
      generally higher than typical antipsychotics, uncertainty exists whether the
      newer atypicals are cost effective alternatives when used in ordinary practice
      settings. AIMS OF THE STUDY: The introduction of newer atypical antipsychotic
      agents has prompted evaluation of their overall effectiveness in reducing health
      care costs given their higher acquisition costs. This paper focuses on the
      effects of differing classes of atypical versus typical antipsychotic medications
      on psychiatric service utilization and cost for persons with serious mental
      illness treated in usual practice settings. METHODS: Descriptive statistics are
      used to compare patient characteristics, service rates and costs across
      psychotropic medication groups. Prediction equations employing ordinary least
      squares regression models are used to explain variation in cost due to pharmacy
      group membership controlling for demographics, clinical diagnoses and symptoms.
      Subjects were 338 Medicaid clients with serious mental illness from Florida,
      Pennsylvania and Oregon treated in ordinary clinical settings. Resource
      utilization and costs were operationalized using administrative databases to
      measure consumption of treatment services and pharmaceuticals for a six month
      period. RESULTS: Inpatient service use was significantly higher for individuals
      on atypical only and combination atypical/typical medications compared to those
      on typical medications only, whereas outpatient use was highest for those on
      typicals. Furthermore, six-month costs for both pharmacy and psychiatric services
      were significantly greater for persons in the atypical only (USD 6528) and
      combination typical/atypical groups (USD 6589) compared to those on typicals only
      (USD 3463). There were still significantly higher costs associated with atypical
      only and the combination typical/atypical users after multivariate controls were
      used. DISCUSSION: This study showed that Medicaid clients in community settings
      using atypical only and typical/atypical combination medications had the highest
      costs both in pharmacy and service use when compared to those on typical only
      medications. However, this study design does not allow us to ascribe a causal
      relationship between medication group and service costs. Given that olanzapine
      was the most recent medication in the compendium of available drugs at the time
      of this study, it is possible that those in the olanzapine only group were
      failing on other drugs. Caution must be used in drawing policy implications
      regarding cost effectiveness of newer medications since individuals who are
      getting the newer atypical or combination medications in community mental health
      center settings may be unstable on the older medications. IMPLICATIONS FOR FUTURE
      RESEARCH: A longer follow-up period is needed to determine if the cohort
      remaining on current atypical medications stabilize over time while those taking
      the newest drug on the market become the most costly population.

PMID- 15998981
TI  - Indicators predicting use of mental health services in Piedmont, Italy.
AB  - BACKGROUND: Since the 1978 Italian reform, an integrated network of community
      mental health services has been introduced. With few exceptions, research on
      determinants of mental health service use at the district level has focused on
      inpatient activities and social deprivation indicators. The European Psychiatric
      Care Assessment Team (EPCAT) standardized methodology allows for an evidence
      based comparison of mental health systems between geographical areas. AIMS: To
      compare service provision and utilization between local catchment areas; to
      explore quantitative relationships between residential and community service use
      and socio-demographic indicators at the ecological level. METHODS: The European
      Socio-demographic Schedule (ESDS) was used to describe area characteristics, and
      the European Service Mapping Schedule (ESMS) to measure service provision and
      utilization in 18 catchment areas in Piedmont. RESULTS: Substantial variation in
      service use emerged. Acute hospital bed occupancy rates were lower in areas with
      more intensive community continuing care service users and with a smaller
      percentage of the population living alone. The non-acute hospital bed occupancy
      rate was directly related to the percentage of the population living alone or in
      overcrowded conditions, and to the level of mobile continuing care service users.
      Community continuing care service use was highest in areas with a larger
      percentage of the population living alone. DISCUSSION: Multiple regression models
      explained between 48 and 55% of the variation in inpatient and community service
      use between areas. Relationships based on ecological characteristics do not
      necessarily apply to the individual. This level of assessment, however, is
      necessary in evaluating mental health policy and service systems, and in
      allocating resources. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The
      distribution of mental health care resources should be weighted in terms of
      indicators of social deprivation shown to be important predictors of both
      inpatient and community service use, as these are likely to be related.
      IMPLICATIONS FOR HEALTH POLICIES: To ensure horizontal equity in access to mental
      health care, particularly for people with severe mental illness, evaluation of
      mental health policy should be based on a concurrent evidence-based assessment of
      the organization and use of both residential and community services, in relation
      to area level indicators of social deprivation. IMPLICATIONS FOR FURTHER
      RESEARCH: Cross-national research using an internationally standardized
      methodology should consider the influence of the social network independently of
      other socio-economic indicators, to verify the relative importance of this in
      predicting service use in southern and in northern European countries.

PMID- 15998982
TI  - The prevalence, course and clinical features of post-concussion syndrome in
      children.
AB  - OBJECTIVE: To investigate the clinical features and the prevalence of symptoms of
      post-concussion syndrome in children with mild traumatic brain injury, and to
      evaluate their changes over time. MATERIAL AND METHODS: The research involved two
      groups of 4-16 year-old children: the case group of 301 children who had
      experienced a single mild traumatic brain injury, and the control group of 301
      children who had sustained any other mild body injury without head trauma. Groups
      were matched according to gender, age, and the date of admission to hospital. In
      total, 102 matched pairs were analyzed. The period between the date of the trauma
      and the examination was one to five years (median-27 months). Standardized
      questionnaires were sent by post to parents from both groups. Parents were asked
      about the health state as well as symptoms of post-concussion syndrome, their
      character and frequency. The respondents were inquired about the presence of the
      symptoms prior to the trauma, shortly after the trauma, and during the last year
      and the last month before the inquiry. RESULTS: The prevalence of headache,
      irritability, fears, sleep disorders, learning difficulties, as well as
      concentration and memory problems did not differ significantly between children
      with mild traumatic brain injury and the control group when the results of the
      last year before examination and the last month before the examination were
      compared. We have investigated how the period of time between the date of the
      trauma and the date when the questionnaire was filled in influenced the results.
      The comparison of the questionnaires that were filled a year (but less than two
      years) after the trauma to those that were filled in 2-5 years after the trauma
      revealed significant differences in the prevalence of a number of symptoms of the
      post-concussion syndrome. In children with mild traumatic brain injury, there was
      a significant decrease in the prevalence of learning difficulties soon after the
      trauma (p=0.032), headaches before (p=0.026) and soon after the trauma (p=0.01),
      and irritability the last month before the examination (p=0.043). In children
      from the control group, there was a significant decrease in the prevalence of
      concentration problems the last year before examination (p=0.023) and the last
      month before examination (p=0.036). CONCLUSIONS: More than one year after the
      trauma, the prevalence of the symptoms of the post-concussion syndrome is not
      significant higher in children with mild traumatic brain injury, compared to
      children with other mild body injuries, and is comparable by the changes over
      time.

PMID- 15998983
TI  - Total hip replacement for the treatment of femoral neck fractures. Long-term
      results.
AB  - OBJECTIVE: To evaluate the outcome of total hip replacement after femoral neck
      fractures and analyze implant survival rates, complication rates, and mortality
      after surgery. MATERIAL AND METHODS: We analyzed 135 primary hip replacements and
      8 revision hip replacements performed in 1991-2003 years. Femoral neck fracture
      was the diagnosis for all primary hip replacements. All patients we analyzed
      prospectively: special form was filled in for every patient participating in the
      study. Personal data, operation data, revision date, diagnosis and complications
      were recorded. Personal patient's identification number was used to determine the
      death date if it was present, and it was checked if the patient was operated on
      in other orthopedic centers. Study ended up on 31st of December, 2003. RESULTS:
      Total cumulative implant survival rate was 92% and 94% for revision because of
      aseptic loosening 10 years postoperatively. Stem survival was 95% for revision
      because of aseptic loosening. Cup survival was 94% for revision because of
      aseptic loosening. Implant type had no influence on survival rates. Dislocation
      rate after hip replacement was 10%. Mortality was 25% at the end of the follow
      up. CONCLUSIONS: Total hip replacement after femoral neck fracture showed high
      implant survival and low additional surgery rate. Total hip replacement after
      femoral neck fracture was associated with high dislocation rate. Low patient's
      mortality rate was associated with relatively lower mean patient's age.

PMID- 15998984
TI  - [Treatment of rectal tumors with transanal endoscopic microsurgery].
AB  - OBJECTIVE: The aim of this study was to assess one and a half years experience
      gained in Lithuania while treating rectal tumors with transanal endoscopic
      microsurgery in the Centre of Abdominal Surgery of Vilnius University Hospital
      "Santariskiu klinikos". MATERIALS AND METHODS: The patients who had rectal
      adenomas and low-risk T1 carcinomas of good or moderate differentiation, with no
      lymphatic and vascular invasion were selected for surgery. Tumor stage was
      determined by transanal endosonoscopy and rectoscopy with multiple macrobiopsies
      before surgery. RESULTS: A total of 47 patients were operated on. The average
      tumor size was 3.4+/-1.4 cm (ranged from 1 to 7 cm). Overall 25 (52.1%)
      carcinomas and 23 (47.9%) adenomas were removed. Pre-operative diagnoses did not
      correspond to the final clinical diagnoses in 14 (29.8%) cases. Forty-three
      (89.6%) radical operations (R0) and 5 (10.6%) doubtful complete operations (RX)
      were performed. One (2.1%) intra-operative complication and one (2.1%) post
      operative complication were observed. After the removal of Ca T2 three patients
      underwent adjuvant radiotherapy. Twenty-six patients were followed up for 3-17
      months after operation: 17 after removal of cancer and 9 after removal of
      adenoma. One (2.1%) recurrence of a tubulovillous adenoma was diagnosed. No other
      complications were reported. CONCLUSIONS: Initial results of transanal endoscopic
      microsurgery obtained while treating rectal adenomas and low-risk T1 cancers are
      promising. The low rate of complications and recurrences in this group offers
      many hopes. The experience of the treatment of T2 cancers with transanal
      endoscopic microsurgery and adjuvant radiotherapy is limited but the results are
      encouraging. It is obvious that the results of randomized and controlled trials
      need to be awaited before definite conclusions can be drawn.

PMID- 15998985
TI  - Generation of superoxide anion by peripheral blood leukocytes in periodontitis
      patients with type 1 diabetes mellitus.
AB  - The involvement of reactive oxygen species in periodontal diseases is unclear.
      The aim of present study was to explore oxidative function of neutrophil
      leukocytes of patients with severe periodontitis who have type 1 diabetes
      mellitus, and control subjects with healthy periodontal tissues and without
      systemic diseases. MATERIALS AND METHODS: The leukocytes for present
      investigation were obtained from peripheral venous blood of 38 patients with
      severe periodontitis who have type 1 diabetes mellitus and 27 control subjects.
      The maximal lucigenin-dependent chemiluminescence and peak time values of
      neutrophils stimulated with non-opsonized Escherichia coli ATCC 25922 and
      Staphylococcus aureus 256 were measured. RESULTS: The maximal lucigenin-dependent
      chemiluminescence of neutrophils of patients with severe periodontitis stimulated
      with non-opsonized E. coli and S. aureus was much higher than that in control
      subjects (p<0.001). In both affected and healthy patients, chemiluminescence of
      neutrophil leukocytes reached its peak value at similar time. The maximum value
      of chemiluminescence of leukocytes stimulated with non-opsonized E. coli in both
      studied groups was reached statistically significantly earlier than when
      stimulating with non-opsonized S. aureus bacteria (p<0.001). CONCLUSION: In
      periodontitis, local non-opsonized bacteria might stimulate neutrophil leukocytes
      to release reactive oxygen species, which can cause inflammation and destruction
      of periodontal tissue.

PMID- 15998986
TI  - [Abnormal gastrointestinal findings in patients with coronary disease revealed by
      endoscopy before cardiac surgery].
AB  - OBJECTIVES: To assess incidence of different abnormal gastrointestinal changes
      revealed by endoscopy before cardiac surgery in different female and male age
      groups and to establish criteria for carrying out preventive endoscopy in
      patients with coronary disease. MATERIAL AND METHODS: Retrospective analysis was
      performed on 3847 patients (63.2% and 36.8% of male and female patients,
      respectively; mean age 61.9+/-11.9) who underwent fiberoptic
      esophagogastroduodenoscopy (FEGDS) before cardiac surgery under extracorporeal
      circulation at Kaunas University of Medicine Hospital in 2000-2003. Study
      population was divided into two groups: group I consisted of 2348 (61%) patients
      whose endoscopy revealed active bleeding from mucous membranes of
      gastrointestinal tract (bleeding gastric or duodenal ulcer) or any other abnormal
      findings indicating bleeding potential (gastric and duodenal erosion or ulcer);
      group II comprised 1499 (39%) patients whose endoscopy revealed no abnormal
      changes or the revealed ones (scars, hiatal hernia, etc.) that cannot cause
      bleeding. RESULTS: No statistically significant differences were established in
      male and female percentage both generally and individually in groups (63.2% and
      36.8% in all population studied; 61% and 39%, 64.6% and 35.4% in group I and
      group II, respectively). Further data analysis showed that FEGDS revealed changes
      requiring pre-surgical treatment in even 62.4% of male patients; meanwhile the
      similar changes were diagnosed in 58.7% of female patients. Incidence analysis of
      abnormal changes in terms of patient age established that even 31.1% of the group
      I population were patients aged 61-70, and 26.5%--patients aged 51-60. It should
      also be noted that these age groups were represented in the most ample manner in
      all population studied--31.7% (1209 patients) and 26.5% (1012 patients),
      respectively. The highest incidence of bleeding potential changes in male
      patients was found in the 51-60 year-old group (30.7% (462 patients)) and 61-70
      year-old group (29% (436 patients)); in female patients, the highest incidence
      was observed in the 61-70 year-old group (35.2% (290 patients)) and 71-80 year
      old group (25.6% (211 patients) (p<0.05). Data analysis showed that just 20.1%
      and 10.9% of male and female patients respectively were diagnosed with the
      changes mentioned in the age groups of up to 50 year-old. The study established
      that only 14.5% of FEGDS carried out revealed no abnormal changes in the upper
      gastrointestinal tract. CONCLUSION: Abnormal gastrointestinal changes indicating
      bleeding potential were established with significantly higher incidence in male
      compared with female patients. Gastrointestinal endoscopy before cardiac surgery
      under extracorporeal circulation should be carried out in 50-70 year-old male
      patients and 60-80 year-old female patients, while carrying out of the same
      examination in the younger and older patients is subject to additional
      indications. Only 14.5% of fiberoptic esophagogastroduodenoscopies carried out
      revealed no abnormal changes in the upper gastrointestinal tract.

PMID- 15998987
TI  - [The evaluation of clinical signs and hormonal changes in women who complained of
      excessive body hair growth].
AB  - OBJECTIVE: To evaluate the clinical signs and hormonal changes in women who
      complained of increased hair growth. MATERIAL AND METHODS: We studied 122 female
      residents of Lithuania aged 18-35 years who were referred to the Clinic of
      Endocrinology of Kaunas University of Medicine Hospital in 2002-2003 for
      excessive body hair growth. Increased body hair was graded using the Ferriman
      Gallwey (F-G) method. Hirsutism was defined when the F-G score was > or =8.
      RESULTS: Hirsutism was present in 74 (60.66 %) females and in 48 (39.34 %) no
      hirsutism was noted. The females with hirsutism complained more frequently of
      infertility (p<0.05), increased greasiness of skin (p<0.05) and noted the
      progressing increase of hair growth (p<0.05). No differences in frequency of
      menstrual disorders and acne were found. The females with hirsutism had
      significantly higher body mass index, systolic and diastolic blood pressure,
      larger waist and hip circumference (p<0.001) and higher waist/hip ratio (p<0.01).
      The significantly higher levels of testosterone and dehydroepiandrosterone
      sulfate (p<0.05), higher values of free androgen index (p<0.001) and
      significantly lower levels of sex hormone-binding globulin (p<0.01) were found in
      females with hirsutism. Women were prone to overestimate the increased hair
      growth, when compared with the physician's assessment (p<0.05). No significant
      difference was found (p>0.05) comparing the mean values of testosterone, sex
      hormone-binding globulin, free androgen index and dehydroepiandrosterone sulfate
      between two groups divided according to the subjective evaluation of excessive
      hair growth by females. CONCLUSIONS: Women are prone to overestimate the
      increased hair growth. The significantly higher levels of testosterone and
      dehydroepiandrosterone sulfate, higher values of free androgen index and lower
      levels of sex hormone binding globulin (p<0.01) were found in females with
      hirsutism. The females with hirsutism complained more frequently of infertility,
      increased greasiness of skin, had higher body mass index, systolic and diastolic
      blood pressure, larger waist and hip circumference and higher waist/hip ratio.

PMID- 15998988
TI  - Incontinentia pigmenti (Bloch-Sulzberger syndrome) in neonates.
AB  - A female newborn presented with emerging skin lesions, systemic eosinophilia, and
      eosinophilic reaction in the skin, liver, lungs, spleen, lymphatic nodes,
      porencephalia, convulsions, and disorders of thermoregulation. In addition to
      that, respiratory and heart failure, as well as brain edema were progressing. The
      suspected diagnosis of incontinentia pigmenti (Bloch-Sulzberger syndrome) was
      confirmed postmortem by skin biopsy.

PMID- 15998989
TI  - [Development of cough-relieving herbal teas].
AB  - Cough-relieving medicinal herbs in tea are used from ancient times. Mucilage
      present in them or secretion produced under the influence of the active
      substances covers the oral and throat mucosa soothing its irritability and
      relieving dry, tiresome cough. It is known that the mixtures of medicinal herbs
      (Specias) have a complex influence on the human organism and the rational
      combination of medicinal herbs can improve their curative action and decrease the
      undesirable side effects. Having summarized the properties of those medicinal
      herbs we decided to create two formulations of cough-relieving herbal tea. The
      first formulation consists of marshmallow roots, liquorice roots and lime
      flowers, the second -- of marshmallow roots, Iceland moss and lime flowers. The
      methods for identification and assay of the active substances in the compounds
      were applied. The purity of the mixtures was regulated by limitation of the loss
      on drying, total ash, microbial contamination, contamination with radionuclides,
      heavy metals, pesticides and foreign matter. The expiry date of both cough
      relieving herbal teas was approved to be 2 years.

PMID- 15998990
TI  - Effects of cadmium and zinc ions on mitotic activity and protein synthesis in
      mouse liver.
AB  - OBJECTIVE: To evaluate the in vivo effects of cadmium and zinc ions on mitotic
      activity and protein synthesis in mouse liver. MATERIAL AND METHODS: White
      outbred mice were injected intraperitoneally with cadmium chloride solution (14
      micromoles cadmium per 1 kg of body mass) and/or with zinc sulfate solution (48
      micromoles zinc per 1 kg of body mass). Histological slides were examined by
      light microscopy. For each specimen, the number of mitotic cells was counted in
      10 randomly selected reference areas. Protein synthesis was evaluated by
      incorporation of [14C]-labeled leucine into newly synthesized peptides and
      proteins. RESULTS: We found that the mitotic index of mouse liver cells was
      increased for periods of 2-8 h after cadmium chloride injection; after 24 h the
      mitotic index significantly diminished. These data indicate a possible increase
      in liver cell regeneration during the initial 8 h following acute cadmium
      exposure. Zinc ions did not affect liver mitotic activity, and, interestingly,
      decreased the mitotic index in the liver of cadmium-treated mice to control
      levels. An examination of the kinetics of protein synthesis in mouse liver over a
      24 h period after cadmium chloride injection revealed that incorporation
      diminished by 38% at 2 h, then increased 51% by 8 h and again decreased by 32% at
      24 h as compared to control. Zinc ions increased protein synthesis in mouse liver
      8 h after zinc sulfate injection. In assessing the effects of cadmium and zinc
      ions in vivo, it appeared that zinc ions tended to protect protein synthesis in
      response to cadmium ions but only at 2 h after cadmium intoxication. CONCLUSIONS:
      Zinc ions are capable of normalizing an increase in the mitotic index of liver
      cells at the early stage of cadmium poisoning (up to 8 h) and to protect the
      liver translation machinery against inhibition by cadmium.

PMID- 15998991
TI  - [Evaluation of occupational risk factors and laboratory workers' health in
      biochemical and clinical laboratories of hospitals of Kaunas city].
AB  - Impact of occupational risk factors on the health of hospital laboratories
      workers is not entirely assessed in Lithuania. Objectives of the study were to
      evaluate the main health disorders of laboratory workers and to define the
      relationship between the health complaints and working conditions in biochemical
      and clinical laboratories. MATERIAL AND METHODS: A cross-sectional
      epidemiological study was conducted in 2002. The questionnaire with questions on
      the most frequent health disorders and main occupational hazards, lifestyle
      factors, etc., was distributed among workers of biochemical and clinical
      laboratories in 6 hospitals of Kaunas city. Odds ratios with significance level
      p< or =0.05 were calculated. RESULTS: 112 laboratory workers completed the
      questionnaire. Laboratory assistants were exposed to higher number of workplace
      hazards rather than other workers. All health complaints were also more prevalent
      among laboratory assistants. Weakness, sleepiness at work, headache and sleep
      disturbances were the most prominent complaints among them to compare with other
      occupations. Skin irritation due to chemicals (chlorine compounds and hydrogen
      peroxide mainly) was more frequent among laboratory assistants as well. The most
      frequent localization of irritation was in hands. Complaints due to eyestrain
      were found in almost one third of responders. Neck pain, back pain, waist pain
      and joint pain due to long lasting fixed position was rather frequent among
      laboratory workers. Inconvenient work posture increased risk for waist pain
      (OR=1.65; p>0.05), neck pain (OR=2.32; p>0.05) and sleep disorders (OR=4.32;
      p<0.05). There was no significant relationship between health disorders and work
      experience. Mental stress is common in job of laboratory workers. CONCLUSIONS:
      More than one third of workers work in inconvenient posture, most of them spent
      in this position more than a half of work time. Inconvenient work position
      significantly increases risk for hand numbness sleep disorders and joint pain.
      Skin irritation and rash, especially in hands, caused by chlorine compounds, soap
      and water is quite common among laboratory workers, mainly assistants. Mental
      stress is common in job of laboratory workers. No statistically significant
      relationship between health complains and work duration was found.

PMID- 15998992
TI  - [Peer reputation of adolescents: sociometric status differences].
AB  - Successful communication with peers, positive classroom acceptance influence
      psychosocial health of children, while social maladjustment in childhood has
      emerged as high risk predictor of later delinquency and conduct problems
      (dropping out of school, criminality, psychopathology). Though these issues have
      devoted increasing attention in recent years, but still there is a lack of
      studies analyzing peer relation of adolescents. The primary purposes of the
      present study were to examine sociometric status, peer reputation and peer
      relations of adolescents and reveal connections between these results. Data were
      obtained on 502 adolescents (mean age 13+/-0.03) attending secondary schools of
      Kaunas city. The findings revealed peer reputation connections with status and
      sex groups.

PMID- 15998993
TI  - [Links between profession and family in the community of Lithuanian pharmacists
      at the end of 19th and the beginning of 20th centuries].
AB  - Little research has been carried out in the sphere of the relations between a
      pharmaceutical career and family in the historiography of pharmacy history. A
      peculiar influence of family on the choice of the pharmaceutical way of life came
      into existence in the period of Lithuanian national revival at the end of the
      19th century and the beginning of the 20th. This article aims to reveal the
      relations between a Lithuanian family and pharmaceutical career, to analyze the
      influence of political, social, economic factors on these relations. At the end
      of the 19th century and the beginning of the 20th the resistance of Lithuanian
      peasants against Russification, Polonification manifested in their objective to
      form Lithuanian intelligentsia. Priestly seminaries became the major centre for
      preparing new Lithuanian intelligentsia. It was prestigious to become a priest.
      Moreover, this profession guaranteed material wealth. Young people often left the
      seminary and started their work in pharmacies where they got a shelter and small
      5 rubles earning of a pharmacy apprentice. Such runaways from parents settled in
      the university cities of czarist Russia and had a purpose to become self
      dependent (i.e. to get education) without parents' support. The choice of a woman
      pharmacist career, however, was greatly influenced by the profession of her
      husband. Some educated Lithuanian pharmacists encouraged their wives to choose
      the same specialty as theirs but such occasions were rare. Sometimes it happened
      so that pharmacists married, but there were only few Lithuanian women-pharmacists
      or assistants of pharmacists, and in the period of Lithuanian national revival
      the point of view on ethnically mixed families was negative. This article
      discusses about the career of women-pharmacists and the influence of family on
      the choice of a profession, as well as Lithuanian point of view on ethnically
      mixed families of pharmacists.

PMID- 15998994
TI  - [Hypertensive emergencies and urgencies].
AB  - Hypertension is one of the most common medical problems affecting approximately 1
      billion individuals worldwide. Severe hypertension that is a potentially life
      threatening condition refers to a hypertensive crisis. Severe hypertension is
      further classified into hypertensive emergencies or hypertensive urgencies.
      Hypertensive emergency refers to a severe hypertension that is associated with
      new or progressive end-organ damage. In these clinical situations, blood pressure
      should be reduced immediately to prevent or minimize organ dysfunction.
      Hypertensive urgency refers to severe hypertension without evidence of new or
      worsening end-organ injury. Blood pressure can be lowered less rapidly in this
      condition. In this review article it is discussed about clinical assessment of
      patients under these conditions, evaluating neurological, cardiovascular, renal
      end-organ damage; how much blood pressure should be lowered, which medication
      should be used to lower blood pressure, treating hypertensive emergencies and
      urgencies; and management of specific conditions (acute intracranial events,
      acute left ventricular dysfunction etc).

PMID- 15998996
TI  - Non-Escherichia coli versus Escherichia coli community-acquired urinary tract
      infections in children hospitalized in a tertiary center: relative frequency,
      risk factors, antimicrobial resistance and outcome.
AB  - BACKGROUND: Currently hospitalization for children with urinary tract infections
      (UTIs) is reserved for severe or complicated cases. Changes may have taken place
      in the characteristics and causative uropathogens of hospital-treated community
      acquired UTI. OBJECTIVES: To study children hospitalized in a tertiary center
      with community-acquired UTI, compare Escherichia coli and non-E. coli UTI, define
      predictors for non-E. coli UTI and elucidate the appropriate therapeutic
      approach. PATIENTS AND METHODS: A prospective clinical and laboratory study from
      2001 through 2002 in a tertiary pediatric medical center. Patients were divided
      by results of the urine culture into E. coli and non-E. coli UTI groups, which
      were compared. RESULTS: Of 175 episodes of culture-proved UTI, 70 (40%) were
      caused by non-E. coli pathogens. Non-E. coli UTI was more commonly found in
      children who were male (P = 0.005), who had underlying renal abnormalities (P =
      0.0085) and who had received antibiotic therapy in the prior month (P = 0.0009).
      Non-E. coli uropathogens were often resistant to antibiotics usually recommended
      for initial therapy for UTI, including cephalosporins and aminoglycosides; 19%
      were initially treated with inappropriate empiric intravenous antibiotics
      (compared with 2% for E. coli UTI, P = 0.0001), with a longer hospitalization.
      CONCLUSIONS: Current treatment routines are often inappropriate for hospitalized
      children with non-E. coli UTI, which is relatively common in this population. The
      defined risk factors associated with non-E. coli UTIs and its antimicrobial
      resistance patterns should be considered to improve empiric antibiotic therapy
      for these infections.

PMID- 15998997
TI  - Epidemiology and diagnosis of hospital-acquired conjunctivitis among neonatal
      intensive care unit patients.
AB  - BACKGROUND: Few recent reports describe the epidemiology and risk factors for
      health care-associated conjunctivitis among neonatal intensive care unit (NICU)
      patients in developed countries. Reporting may be inaccurate in this population
      given that the National Nosocomial Infection Surveillance System (NNIS)
      definition is largely dependent on a positive culture, whereas clinical practice
      often consists of empiric treatment. OBJECTIVES: We describe the epidemiology of
      conjunctivitis among neonates in 2 level III-IV NICUs and compare the NNIS
      definition with our study definition: eye drainage and empiric treatment with or
      without a culture. METHODS: Patient demographics, clinical, device usage and
      conjunctivitis data collected prospectively from March 2001 through January 2003
      were analyzed. RESULTS: Conjunctivitis occurred in 5% (n = 154/2935) of infants,
      of whom 51% (n =79) were in NICU 1 and 49% (n =75) in NICU 2. Predominant
      pathogens included coagulase-negative staphylococci (25%), Staphylococcus aureus
      (19%) and Klebsiella spp. (10%). Significant predictors of conjunctivitis
      included low birth weight, use of ventilator or nasal cannula continuous positive
      airway pressure and study year. Ophthalmologic examination was an additional
      predictor of infection in NICU 1. Eye examination data were unavailable for NICU
      2. Only 62% of cases that met the study definition for conjunctivitis met the
      NNIS definition, because many infants received empiric treatment. CONCLUSIONS:
      Clinical conjunctivitis was associated with low birth weight and patient care
      factors that could lead to contamination of the eye with respiratory tract
      secretions. The NNIS definition failed to detect 38% of clinical infections.
      Consideration should be given to revising the definition of conjunctivitis for
      the NICU population.

PMID- 15998998
TI  - Neonatal sepsis in Egypt associated with bacterial contamination of glucose
      containing intravenous fluids.
AB  - BACKGROUND: Rates of sepsis exceeding 50% in a neonatal intensive care unit
      (NICU) in Cairo, Egypt, were not controlled by routine antimicrobial therapy. We
      investigated these conditions in September 2001. METHODS: Case series and
      retrospective cohort studies were conducted on 2 groups of NICU infants admitted
      to an academic medical center between February 12 and July 31, 2001. Observation
      of clinical practices led us to culture in-use intravenous (i.v.) fluids and
      medications. We monitored rates of i.v. fluid contamination, clinical sepsis and
      mortality after interventions to establish new procedures for handling and
      disposal of i.v. fluids, infection control training and improved clinical
      laboratory capacity. RESULTS: Among infants in the retrospective cohort group, 88
      (77%) of 115 had clinical sepsis, and 59 (51%) died. In the case series group, we
      documented the time of initial positive blood culture; 21 (64%) of 33 were septic
      <24 hours after birth. Klebsiella pneumoniae accounted for 24 (73%) of 33
      isolates; 14 (58%) of 24 were extended spectrum beta-lactamase-producing and
      aminoglycoside-resistant. On admission, all neonates received glucose-containing
      i.v. fluids; i.v. bottles (500 mL) were divided among multiple infants. The i.v.
      fluids were prepared at the bedside; poor hand hygiene and poor adherence to
      aseptic techniques were observed. K. pneumoniae was isolated from 13 (65%) of 20
      in-use glucose-containing i.v. fluids. Fluid contamination, sepsis and mortality
      rates declined significantly after intervention. CONCLUSION: Extrinsically
      contaminated i.v. fluids resulted in sepsis and deaths. Standard infection
      control precautions significantly improve mortality and sepsis rates and are
      prerequisites for safe NICU care.

PMID- 15998999
TI  - Age-related standards for total lymphocyte, CD4+ and CD8+ T cell counts in
      children born in Europe.
AB  - OBJECTIVE: Currently used reference values for immunologic markers in children
      are largely derived from cross-sectional data from historic, small sample size
      studies in predominantly white children. There is a lack of reliable age-related
      standards for immunologic markers, such as CD4+ cell counts, in particular in
      black children whose values according to recent reports may differ from those in
      white children. Standards are essential for diagnosing and monitoring childhood
      diseases such as pediatric human immunodeficiency virus (HIV) infection. DESIGN:
      Prospective cohort study with data on 1781 uninfected children born to HIV
      infected mothers in the European Collaborative Study. METHODS: Age-related
      standards (centiles) for immunologic markers (CD4+ and CD8+ cell counts and total
      lymphocyte counts) up to 5 years in black and up to 10 years in white children
      were constructed using Generalized Additive Models for Location, Scale and Shape
      method, which allows for variability and skewness of the data. The optimal model
      was chosen according to the Akaike Information Criterion. RESULTS: Patterns and
      values of total lymphocyte, CD4+ and CD8+ cell counts varied with age, especially
      in the first 3 years of life, but less so thereafter. Values of all 3 immunologic
      markers were substantially and significantly lower in black than in white
      children of the same age. CONCLUSIONS: We present age-related standards
      separately for black and white children to aid clinicians in the monitoring of
      childhood diseases. These standards may also contribute to the decision on an
      accurate cutoff for CD4+ cell counts for initiating treatment of HIV-infected
      children.

PMID- 15999000
TI  - Determining risk factors for candidemia among newborn infants from population
      based surveillance: Baltimore, Maryland, 1998-2000.
AB  - BACKGROUND: Our objective was to determine risks factors for late onset
      candidemia, independent of birth weight, in newborn infants. METHODS: We
      performed a matched case-control study. Cases were identified through active,
      population-based surveillance for candidemia, conducted in Baltimore City and
      County during 1998-2000, and were defined as the incident isolation of any
      Candida species from the bloodstream of an infant 3 months old or younger. Four
      controls, matched by age, hospital, birth weight category, hospital stay and
      admission date, were selected for each case. Potential risk factors included
      clinical, demographic and maternal prenatal data. RESULTS: Of the 35 cases, 19
      (54%) infections were with Candida albicans, 9 (26%) were with Candida
      parapsilosis and 5 (14%) were with Candida glabrata. Cases had a median birth
      weight of 680 g (range, 430-3200 g); median gestational ages of cases and
      controls were 25 and 27 weeks, respectively. Compared with controls, cases had
      significant higher mortality (20% versus 4%; P = 0.004). No maternal factors were
      associated with increased risk of disease; cases were as likely as controls to be
      of black race. Multivariable conditional logistic regression analysis revealed
      that gestational age younger than 26 weeks [adjusted odds ratio, 6.5; 95%
      confidence interval (95% CI), 1.3-32], vaginal delivery (adjusted odds ratio,
      4.3; 95% CI 1.3-14.2) and abdominal surgery (adjusted odds ratio, 10.9; 95% CI
      1.9-62) were independently associated with increased risk of candidemia.
      CONCLUSIONS: Independent of birth weight, infants born at <26 weeks or those who
      have had abdominal surgery are at a significantly increased risk of candidemia.
      This study helps define a subgroup of preterm infants at high risk of developing
      bloodstream infections with Candida species.

PMID- 15999001
TI  - Single versus dual respiratory virus infections in hospitalized infants: impact
      on clinical course of disease and interferon-gamma response.
AB  - BACKGROUND: Dual respiratory viral infections are frequently associated with
      lower respiratory tract illness in infants. This study aimed to determine the
      impact of a dual respiratory viral infection on specific aspects of the infant's
      immune response and the clinical course of illness. METHODS: A prospective study
      was performed with 772 infants hospitalized from October 2000 through July 2004.
      Sensitive polymerase chain reaction methodology revealed the presence of a single
      respiratory virus in 443 (57%) of 772 cases, whereas dual infections were
      identified in 153 (20%) of cases. From 250 infants with confirmed respiratory
      viral infection, fresh heparinized blood was analyzed for interferon-gamma (IFN
      gamma) responses by flow cytometry. Of these, 191 patients had a single infection
      with respiratory syncytial virus (RSV), rhinoviruses, adenoviruses or influenza
      viruses; and 59 patients had a dual infection with RSV and rhinoviruses, RSV and
      adenoviruses, influenza viruses and rhinoviruses or adenoviruses and
      rhinoviruses. The clinical features and peripheral lymphocyte IFN-gamma responses
      were compared among infants with single or dual infections. RESULTS: It was found
      that dual infections with non-RSV respiratory viruses induced peripheral blood
      mononuclear cell IFN-gamma responses that mimic those of single infections,
      whereas coinfection with RSV was associated with reduced IFN-gamma responses and
      a more severe clinical course of lower respiratory tract disease. CONCLUSIONS:
      The results indicate that the clinical characteristics and the IFN-gamma response
      differ significantly in single and dual respiratory viral infection, depending on
      the nature of the simultaneously detected viruses. In dual infections, RSV
      involvement was associated with a decreased IFN-gamma response in peripheral
      blood mononuclear cell and an increase in severity of illness.

PMID- 15999002
TI  - Frequency of detection of picornaviruses and seven other respiratory pathogens in
      infants.
AB  - BACKGROUND: Previous studies in which molecular-based techniques have been used
      to identify the causative pathogens of respiratory tract infection have
      investigated hospitalized children only. We report a prospective study designed
      to determine the frequency and clinical presentation of community-acquired
      respiratory illness in infancy associated with 8 common respiratory pathogens.
      METHODS: Eighty-eight infants were monitored through their first winter. With
      each respiratory illness, infants were examined, and a nasal lavage specimen was
      collected. Individual reverse transcription-polymerase chain reactions were
      performed to detect infection with picornaviruses (rhinoviruses and
      enteroviruses), coronaviruses (serotypes OC43 and 229E), adenoviruses,
      parainfluenza viruses 1-3, influenza viruses (types A and B), respiratory
      syncytial virus (RSV), Chlamydia pneumoniae and Mycoplasma pneumoniae. RESULTS:
      Picornaviruses were the most frequently detected pathogen identified in 46% (56
      of 123) of episodes, followed by RSV (27%), parainfluenza viruses (13%) and
      coronaviruses (9%). Dual pathogen infections were identified in 20% of episodes,
      predominantly caused by picornaviruses together with either RSV or parainfluenza
      viruses. RSV infection was significantly associated with a diagnosis of
      bronchiolitis. No other associations were found between pathogen and clinical
      diagnosis. Dual infection did not predispose infants to a more severe clinical
      course. CONCLUSIONS: Picornaviruses are the predominant cause of community
      acquired respiratory tract infection in the first year of life. Large prospective
      community-based studies will be needed to fully evaluate the contribution of
      picornaviruses, both in isolation and in combination with other respiratory
      pathogens, to the various clinical syndromes of respiratory infection observed
      during infancy.

PMID- 15999004
TI  - Increasing clindamycin resistance among methicillin-resistant Staphylococcus
      aureus in 57 northeast United States military treatment facilities.
AB  - BACKGROUND: Increasing community-acquired methicillin-resistant Staphylococcus
      aureus (CA-MRSA) has led many to use clindamycin for CA-MRSA disease, whereas
      others suggest caution because of inducible clindamycin resistance and rely on
      drugs such as trimethoprim-sulfamethoxazole (TMP-SMX). AIM: To analyze the change
      in antibiotic susceptibility pattern of S. aureus isolates from 2001 to 2004 in a
      closed health care system, a period during which clindamycin and TMP-SMX use
      increased 99 and 62%, respectively. METHODS: S. aureus cultures from 57 military
      hospitals and clinics from 2001-2002 and 2003-2004 were compared for body site
      and antibiotic sensitivity, particularly the potentially inducible clindamycin
      susceptible erythromycin-resistant pattern. A portion was evaluated by a double
      disk diffusion test (D test). RESULTS: Numbers of S. aureus-positive cultures
      obtained from "wound" sites rose significantly in both pediatric (138 to 215, P <
      0.001) and adult (715 to 972, P < 0.001) isolates, with a rise in MRSA in
      children (6 of 138 to 60 of 215, P < 0.001) and in adults (161 of 715 to 324 of
      972, P < 0.001). Clindamycin resistance increased among pediatric S. aureus
      isolates (1 of 207 to 13 of 327, P < 0.05), whereas >96% remained TMP-SMX
      susceptible. Five methicillin-susceptible S. aureus (MSSA), 2 MRSA of 41
      pediatric and 36 MSSA, 43 MRSA of 437 adult S. aureus specimens were D test
      positive. CONCLUSIONS: In late 2004, most S. aureus from our region are still
      beta-lactam-susceptible. Most of the MRSA are still susceptible to clindamycin
      and do not appear to have inducible resistance. We must closely monitor the rates
      of constitutive and inducible clindamycin resistance as well as consider
      treatment alternatives that may slow the rate of clindamycin resistance.

PMID- 15999003
TI  - Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus
      in healthy children.
AB  - BACKGROUND: Prior studies, including one from our institution performed in 2001,
      suggest that nasal colonization with methicillin-resistant Staphylococcus aureus
      (MRSA) occurs infrequently in the healthy pediatric population (0.2-2.2%).
      However, infections caused by community-associated MRSA have increased remarkably
      in recent years. As a result, we restudied the prevalence of MRSA nasal
      colonization in healthy children, comparing results from 2001 and 2004. PATIENTS
      AND METHODS: Nasal swabs were collected from 500 children presenting for health
      maintenance visits. Samples were cultured quantitatively, and MRSA isolates were
      confirmed by growth on selective media, coagulase testing and the presence of the
      mecA resistance gene. MRSA isolates were further analyzed for antibiotic
      susceptibilities, genetic relatedness by pulsed field gel electrophoresis and
      polymerase chain reaction for the detection of the gene encoding Panton-Valentine
      leukocidin. RESULTS: There were 182 children (36.4%) colonized with S. aureus,
      and 46 (9.2%) colonized with MRSA. This is significantly higher than the MRSA
      colonization rate in 2001 (0.8%; P < 0.001). There were no significant
      associations between potential risk factors and MRSA colonization except for
      having a family member work in a hospital (odds ratio, 2.0; 95% confidence
      interval, 1.03-4.1). Pulsed field gel electrophoresis revealed heterogeneity of
      circulating strains, and the Panton-Valentine leukocidin gene locus was detected
      in 10 of 46 MRSA isolates (22%). CONCLUSION: Nasal MRSA colonization in healthy
      children in Nashville has increased significantly in the past 3 years. As
      colonization typically precedes infection, this increase may be a major factor in
      the emergence of community-associated MRSA as a pathogen of healthy children.

PMID- 15999005
TI  - Significance of extreme leukocytosis in the evaluation of febrile children.
AB  - BACKGROUND: Emergency department evaluation of young febrile children often
      includes a white blood cell count. Although a high white blood cell count is
      associated with an increased likelihood of infection, the clinical significance
      of extreme leukocytosis (EL), defined as a white blood cell count of > or =
      25,000/mm, has not been well-studied. OBJECTIVE: To determine diagnoses
      associated with EL in febrile children evaluated in a pediatric emergency
      department and to compare rates of serious bacterial infection in those with EL
      and in those with more modest leukocytosis (LK) (15,000-24,999/mm). METHODS: A
      retrospective case-control study of children 2-24 months of age was performed.
      Those with EL were frequency age- and gender-matched to controls with LK.
      RESULTS: Sixty-nine patients with EL and 94 patients with LK were included. The
      mean age was 9.9 months, and 91 (56%) patients were male. The diagnoses were
      similar between the 2 groups, with otitis media, viral syndrome and pneumonia
      being the most common. The rates of proven serious bacterial infection were
      similar between EL (25%; 95% confidence interval, 15-36%) and LK (17%; 95%
      confidence interval, 10-26%) patients. Using different white blood cell cutoff
      points did not distinguish between patients with and without serious bacterial
      infection. CONCLUSION: Young febrile children whose emergency department
      evaluation revealed EL had diagnoses and rates of serious bacterial infection
      similar to those of children with LK.

PMID- 15999006
TI  - Middle ear fluid Streptococcus pneumoniae serotype distribution in Costa Rican
      children with otitis media.
AB  - BACKGROUND: Streptococcus pneumoniae conjugate vaccine became available in Costa
      Rica in 2004. Previous S. pneumoniae middle ear fluid (MEF) data obtained during
      the period 1999-2001 from Costa Rican children indicated that serotype 19F was
      the most common type (75%), but more recently other serotypes have become more
      prevalent. OBJECTIVES: To establish the most common S. pneumoniae serotypes
      present in the MEF of Costa Rican children with otitis media (OM) and to analyze
      serotype distribution by demographic factors, disease distribution and
      antimicrobial susceptibility patterns and assess the potential protection
      provided by the new conjugated heptavalent S. pneumoniae vaccine in Costa Rican
      children with OM. METHODS: During 2002 and 2003, 69 S. pneumoniae isolates were
      obtained from the MEF of Costa Rican children, ages 3-49 months, with OM.
      Serotyping was performed by the quellung reaction with antisera from Statens
      Serum Institute, Copenhagen, Denmark. RESULTS: The most common S. pneumoniae
      serotypes isolated were 19F (26.1%), 6B (14.5%), 9V (8.7%), 16F (8.7%), 14
      (5.8%), 23F (5.8%), 3 (5.8%) and 6A (5.8%). Serotype distribution was similar
      among children younger than 24 months of age or 24 months of age or older and by
      disease distribution. There was a tendency towards more penicillin- and
      trimethoprim-sulfamethoxazole-nonsusceptible isolates among vaccine-type strains
      than among non-vaccine type strains. CONCLUSIONS: The serotype distribution of S.
      pneumoniae causing pediatric OM in Costa Rica is similar to those reported from
      developed countries. The current heptavalent pneumococcal conjugate vaccine
      covers 74% of OM episodes in Costa Rican children.

PMID- 15999007
TI  - Very low birth weight preterm infants with early onset neonatal sepsis: the
      predominance of gram-negative infections continues in the National Institute of
      Child Health and Human Development Neonatal Research Network, 2002-2003.
AB  - BACKGROUND: Early onset neonatal sepsis (EOS, occurring in the first 72 hours of
      life) remains an important cause of illness and death among very low birth weight
      (VLBW) preterm infants. We previously reported a change in the distribution of
      pathogens associated with EOS from predominantly gram-positive to primarily gram
      negative organisms. OBJECTIVE: To compare rates of EOS and pathogens associated
      with infection among VLBW infants born at centers of the National Institute of
      Child Health and Human Development (NICHD) Neonatal Research Network during 3
      time periods: 1991-1993; 1998-2000; and 2002-2003. STUDY DESIGN: Prospectively
      collected data from the NICHD Neonatal Research Network VLBW registry were
      retrospectively reviewed. Rates of blood culture confirmed EOS, selected maternal
      and infant variables and pathogens associated with infection were compared
      between 2002-2003 and 2 previously published cohorts. RESULTS: During the past 13
      years, overall rates of EOS have remained stable (15-19 per 1000 live births of
      infants 401-1500 g). More than one-half of early infections in the 2002-2003
      cohort were caused by gram-negative organisms (53%), with Escherichia coli the
      most common organism (41%). Rates of group B streptococcal infections remain low
      (1.8 per 1000 live births). Between 1991-1993 and 1998-2000, there was a
      significant increase in rates of E. coli infections; but in 2002-2003, there was
      no significant change (7.0 per 1000 live births). Infants with EOS continue to be
      at significantly increased risk for death compared with uninfected infants.
      CONCLUSION: EOS remains an uncommon but important cause of morbidity and
      mortality among VLBW infants. Gram-negative organisms continue to be the
      predominant pathogens associated with EOS.

PMID- 15999008
TI  - Nitazoxanide for treatment of intestinal parasites in children.

PMID- 15999009
TI  - Innate immunity, Toll-like receptors and host response to infection.

PMID- 15999010
TI  - Detection of human coronavirus-NL63 in children in Japan.
AB  - Human coronavirus NL63 recently found in The Netherlands has been detected in
      Japan with a reverse transcription-polymerase chain reaction technique in
      clinical specimens from pediatric patients with respiratory symptoms. Of 419
      specimens that were negative for common respiratory viruses, 5 were positive for
      human coronavirus NL63, and these specimens were all collected in the first 3
      months of 2003.

PMID- 15999011
TI  - Rotavirus epidemiology in San Luis Potosi, Mexico.
AB  - The epidemiology of rotavirus infections was investigated in San Luis Potosi,
      Mexico during a 6-year period. In each of the study years, the epidemic period
      started in October or November; peak activity was detected between December and
      February, and the end of the epidemic occurred in March or April. Rotavirus
      infections show a consistent temporal pattern in our community.

PMID- 15999012
TI  - Outbreak of extended spectrum beta-lactamase-producing Klebsiella pneumoniae
      infection in a neonatal intensive care unit related to onychomycosis in a health
      care worker.
AB  - Four cases of infection by extended spectrum beta-lactamase-producing Klebsiella
      pneumoniae occurred in the neonatal intensive care unit. Isolation, empiric
      therapy change and education produced no effect. Newborn weekly colonization
      rates were 0-18.7%. One health care worker with onychomycosis was positive for
      extended spectrum beta-lactamase-producing K. pneumoniae. Isolates were identical
      by molecular typing. Outbreak was controlled when the health care worker was
      excluded from the neonatal intensive care unit.

PMID- 15999013
TI  - Fetal breech presentation predisposes to subsequent development of septic
      arthritis of the hip.
AB  - We postulated a link between breech presentation and septic arthritis of the hip.
      To examine the potential association between these 2 relatively uncommon
      entities, we used the Patient Administration Systems and Biostatistics Activity
      (PASBA) database, which contains coded information derived from hospitalizations
      and ambulatory encounters at U.S. military hospitals worldwide. Among a cohort of
      nearly 1 million infants born in a 14-year period, 3.37% were found to be in the
      breech presentation. The rate of septic arthritis of the hip or pelvis during the
      first year of life among these breech infants was approximately 1/8000, providing
      a relative risk of 4.1 (95% confidence interval, <1.4-11.7) compared with the
      rate among nonbreech infants. Fetal breech presentation predisposes to the
      development of septic hip during the first year of life.

PMID- 15999014
TI  - Hepatitis A virus infection presenting with seizures.
AB  - Hepatitis A infection rarely causes extrahepatic manifestations. Here we present
      a 5-year-old patient with an initial complaint of nuchal rigidity and convulsions
      during the course of hepatitis A infection. Because hepatitis A virus RNA was
      demonstrated in the cerebrospinal fluid, it was thought that convulsions might be
      related to this viral infection.

PMID- 15999015
TI  - Congenital cytomegalovirus infection diagnosed by polymerase chain reaction with
      the use of preserved umbilical cord.
AB  - We report a patient with congenital cytomegalovirus infection diagnosed
      retrospectively by real time polymerase chain reaction with the use of a
      preserved umbilical cord. The patient had mild developmental delay without
      apparent hearing loss at the diagnosis. Congenital cytomegalovirus infection was
      suspected on the basis of magnetic resonance imaging that showed abnormal signal
      intensities in the gray-white matter junction.

PMID- 15999016
TI  - Photobacterium damsela bacteremia in a child with sickle-cell disease.
AB  - Photobacterium damsela was identified in a blood culture taken from a child with
      sickle-cell disease. This is the first report of this organism in humans in the
      Caribbean. The microbiology of this organism and its identification are
      discussed. The clinical presentation in humans and the role of the immune status
      of the patient are reviewed.

PMID- 15999017
TI  - Detection of human metapneumovirus from children with acute otitis media.
AB  - Nasal and middle ear specimens collected from children with acute otitis media
      were subjected to viral isolation and bacteria culture. All virus-negative
      specimens underwent reverse transcription polymerase chain reaction to detect
      human metapneumovirus. Three of 126 middle ear specimens were positive by this
      assay.

PMID- 15999018
TI  - Acute hydrocephalus caused by mumps meningoencephalitis.
AB  - Hydrocephalus is a rare complication of mumps. We report an 8.5-year-old boy with
      acute hydrocephalus associated with mumps meningoencephalitis.

PMID- 15999019
TI  - Nine-year-old girl with lymphangiectasia and chest pain.

PMID- 15999021
TI  - In vitro activity of tetracyclines against Helicobacter pylori isolates from
      Japanese children.

PMID- 15999020
TI  - Multiorgan echinococcosis in a pediatric patient.

PMID- 15999024
TI  - Sharing memories: the brain and the immune system.

PMID- 15999026
TI  - Brain-immune interactions in neuropsychiatry: highlights of the basic science and
      relevance to pathogenic factors and epiphenomena.
AB  - Unraveling the significant complexity of brain-immune interactions could provide
      essential new insights and potential treatment considerations for the clinical
      neurosciences. Despite considerable research relating immunological changes to
      major neuropsychiatric disorders, it has been difficult to establish that
      immunological processes are involved in the development of central nervous system
      pathology associated with these disorders. This brief article highlights some of
      the landmark basic studies and seeks to convey essential principles guiding
      research in brain-immune interactions. Research in this area often incorporates
      several disciplines, ranging from psychology and neuroscience to immunology and
      molecular genetics. The clinical implications of this area of research are
      discussed, with emphasis on the challenge of disentangling pathogenic factors and
      valid markers of disease from epiphenomena.

PMID- 15999022
TI  - Etiology of diarrhea in pediatric outpatient settings.

PMID- 15999027
TI  - An abbreviated review of immune abnormalities in schizophrenia.
AB  - Initial investigations of the possible interaction between schizophrenia and the
      immune system began in the early 1900s and have proceeded in a rather halting
      fashion because of the methodological challenges faced by investigators. However,
      a confluence of recent data suggests that activation of the inflammatory response
      system, the cellular immune system, and the humoral immune system may be present
      in some patients with schizophrenia. Some of the most compelling data support the
      hypothesis that minor levels of immune activation may be associated with acute
      psychotic exacerbations. However, a second body of evidence suggests that some
      individuals with schizophrenia may have chronic, evolving autoimmune processes.
      This article is an overview of the history, rationale, and some of the recent
      findings on the interaction between schizophrenia and the immune system.

PMID- 15999028
TI  - Rasmussen's syndrome: intractable epilepsy and progressive neurological
      deterioration from a unilateral central nervous system.
AB  - Rasmussen's syndrome (chronic encephalitis with epilepsy) is a rare neurological
      disorder of unknown cause characterized by severe epilepsy, hemiplegia, dementia,
      and inflammation of the brain, and progressive functional and structural
      destruction of a single cerebral hemisphere. While one mechanism underlying the
      pathogenesis of Rasmussen's encephalitis has been hypothesized to be mediated by
      production of excitotoxic GluR3 autoantibodies to the a-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) receptor, other neuropathological
      etiologies have also been indicated. Proposed therapies have included
      antiepileptics, steroids, antiviral agents, alpha-interferon, and immunoglobulin.
      The mainstay of therapy is surgical hemispherectomy. To date, no medical
      therapies have permanently halted neurologic deterioration.

PMID- 15999029
TI  - Stiff-person syndrome: autoimmunity and the central nervous system.
AB  - Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle
      stiffness in the spine and lower extremities with superimposed muscle spasms
      triggered by external stimuli. Patients with SPS are often referred for
      psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS.
      Psychosocial stressors often precede the first manifestations of the disease;
      depression, anxiety, and alcohol abuse are comorbid illnesses. The identification
      of an association with antibodies to glutamic acid decarboxylase (GAD) was
      invaluable for definitively establishing a pathological basis for the disease;
      antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much
      lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target
      GAD-expressing neurons for immune-mediated destruction, are part of a wider
      immune process, or are merely a marker for destruction of GAD-expressing neurons
      by an independent neurodegenerative process is not yet clear. Both
      electromyography and the detection of GAD antibodies are useful in establishing a
      diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies
      (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with
      benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid
      withdrawal from therapy should be avoided.

PMID- 15999030
TI  - The PANDAS subgroup: recognition and treatment.
AB  - A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD)
      has been identified who share a common clinical course characterized by dramatic
      symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS)
      infections. The term PANDAS has been applied to the subgroup, to indicate the
      postulated etiology of their symptoms: Pediatric Autoimmune Neuropsychiatric
      Disorders Associated with Streptococcal infections. Five clinical characteristics
      define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal
      symptom onset, sudden onset or abrupt exacerbations (sawtooth course),
      association with neurological abnormalities (presence of adventitious movements
      or motoric hyperactivity during exacerbations), and temporal association between
      symptom exacerbations and GABHS infections. Post-streptococcal symptom
      exacerbations are typically quite dramatic, with patients reporting that their
      symptoms "...came on overnight" or "...appeared all of a sudden a few days after
      I had a sore throat." The post-streptococcal inflammatory nature of the
      neuropsychiatric symptoms provides novel opportunities for treatment and
      prevention, including immunomodulatory therapies such as therapeutic plasma
      exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed
      placebo-controlled trial revealed that both IVIG and TPE were effective in
      reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively)
      for a group of severely ill children with OCD and/or tic disorders. Further
      research is required to determine why the treatments are helpful, as well as to
      ascertain whether or not antibiotic prophylaxis can help prevent post
      streptococcal symptom exacerbations.

PMID- 15999032
TI  - Maintenance of certification: a message from the American Board of Thoracic
      Surgery (ABTS).

PMID- 15999033
TI  - Vascular remodeling as a biologic principle: is the ulnar artery an exception?

PMID- 15999034
TI  - Chronic compensatory increase in ulnar flow and accelerated atherosclerosis after
      radial artery removal for coronary artery bypass.
AB  - BACKGROUND: Only scant information is available on the chronic consequences of
      radial artery removal for coronary artery bypass surgery on forearm circulation.
      METHODS: Twenty-five patients submitted to radial artery removal for coronary
      artery bypass were submitted to serial Doppler echocardiographic evaluation of
      the flow and morphology of the forearm arteries. RESULTS: The peak systolic
      velocity of the ulnar artery of the operated side was significantly higher than
      that of the control site. The intimal-medial thickness of the ulnar artery was
      always significantly higher on the operated side, and this difference reached
      statistical significance at 10 years' follow-up. There was a significantly higher
      prevalence of atherosclerotic plaques in the ulnar artery of the operated versus
      control arm (7/25 vs 0/25, P = .03). CONCLUSION: Radial artery removal for
      coronary artery bypass surgery leads to a chronic increase in ulnar flow
      accompanied by increased intimal-medial thickness and accelerated atherosclerotic
      disease. These findings might have potentially important implications for
      surgical indications and patient management.

PMID- 15999035
TI  - Mitral mechanical replacement in young rheumatic women: analysis of long-term
      survival, valve-related complications, and pregnancy outcomes over a 3707-patient
      year follow-up.
AB  - OBJECTIVE: A follow-up study was performed to assess long-term survival, valve
      related complications, and pregnancy outcomes in young rheumatic women undergoing
      isolated mitral mechanical replacement. The influence of prosthetic type on
      outcomes was also investigated. METHODS: Between 1975 and 2003, 267 isolated
      mitral mechanical prostheses were implanted. Follow-up reached 3707.8 patient
      years. RESULTS: Actuarial survival at 1, 5, 10, 15, 20, and 25 years was 97% +/-
      0.01%, 90.4% +/- 0.017%, 85.3% +/- 0.023%, 82.3% +/- 0.025%, 71.7% +/- 0.036%,
      and 70.2% +/- 0.038%, respectively. At multivariate analysis, atrial fibrillation
      at follow-up was identified as an independent risk factor for late mortality,
      whereas left ventricular ejection fraction at 12 postoperative months proved to
      be a protective factor. Freedom from thromboembolism at 1, 5, 10, 15, 20, and 25
      years was 98.1% +/- 0.01%, 94.1% +/- 0.015%, 89.1% +/- 0.021%, 85.9% +/- 0.025%,
      81.1% +/- 0.031%, and 75.3% +/- 0.063%, respectively. Atrial fibrillation and
      Carbomedics device were significantly associated with an increase in
      thromboembolic events. Freedom from reoperation at 1, 5, 10, 15, 20, and 25 years
      was 99.2% +/- 0.005%, 95% +/- 0.014%, 91.6% +/- 0.018%, 88.6% +/- 0.022%, and
      85.7% +/- 0.041%. Type of prosthesis (tilting disc) was identified as a predictor
      of reoperation. At the end of the study, 208 patients were still alive: 94.7%
      were in New York Heart Association class I or II. When receiving warfarin
      therapy, no patient undertaking pregnancy (n = 35) experienced adverse cardiac or
      valve-related events. Fetal events were significantly less frequent with a daily
      warfarin dose less than 5 mg. CONCLUSIONS: Mechanical devices provided excellent
      performance, safety, and durability. The prognostic role of left ventricular
      function and atrial fibrillation overwhelmed any differences that might exist
      between different prosthetic designs. Pregnancies entail virtually no maternal
      risk and predictable fetal complications.

PMID- 15999036
TI  - Safety, efficacy, and cost of intraoperative cell salvage and autotransfusion
      after off-pump coronary artery bypass surgery: a randomized trial.
AB  - OBJECTIVE: We evaluated, in a randomized controlled trial, the safety and
      effectiveness of intraoperative cell salvage and autotransfusion of washed
      salvaged red blood cells after first-time coronary artery bypass grafting
      performed on the beating heart. METHODS: Sixty-one patients undergoing off-pump
      coronary artery bypass grafting surgery were prospectively randomized to
      autotransfusion (n = 30; receiving autotransfused washed blood from
      intraoperative cell salvage) or control (n = 31; receiving homologous blood only
      as blood-replacement therapy). Homologous blood was given according to unit
      protocols. RESULTS: The groups were well matched with respect to demographic and
      comorbid characteristics. Patients in the autotransfusion group had a
      significantly higher 24-hour postoperative hemoglobin concentration (11.9 g/dL;
      SD, 1.41 g/dL) than those in the control group (10.5 g/dL; SD, 1.37 g/dL) (mean
      difference, 1.02 g/dL; 95% confidence interval, 1.60-0.44 g/dL; P = .0007), as
      well as a 20% reduction in the frequency of homologous blood product use (11/31
      vs 5/30; P = .095). Autotransfusion of washed red blood cells was not associated
      with any derangement of thromboelastograph values or laboratory measures of
      clotting pathway function (prothrombin time, activated partial thromboplastin
      time, and fibrinogen levels), increased postoperative bleeding, fluid
      requirements, or adverse clinical events. There was no statistical difference
      between groups in the total operation, hospitalization, and management costs per
      patient (median difference, USD 1015.90; 95% confidence interval, -USD 2260 to
      USD 206; P = .11). Conclusions Intraoperative cell salvage and autotransfusion
      was associated with higher postoperative hemoglobin concentrations, a modest
      reduction in transfusion requirements, no adverse clinical or coagulopathic
      effects, and no significant increase in cost compared with controls. This study
      supports its routine use in off-pump coronary artery bypass grafting surgery.

PMID- 15999037
TI  - Atherosclerosis of the aorta is common in patients with severe aortic stenosis:
      an intraoperative transesophageal echocardiographic study.
AB  - OBJECTIVE: Several studies have recently reported an association between aortic
      valve calcification and atherosclerosis of the cardiovascular system, suggesting
      that aortic valve calcification might represent an atherosclerosis-like process.
      Hence the aim of the present study was to determine whether there is a similar
      association between aortic stenosis and aortic atheromas. METHODS: We evaluated
      the records and echocardiographic videotapes of 91 consecutive patients with
      severe aortic stenosis who underwent intraoperative transesophageal
      echocardiography before aortic valve replacement to measure the presence and
      characteristics of aortic atheromas. There were 50 men (55%) and 41 women (45%).
      The mean age was 71.9 +/- 9.4 years (range, 34-91 years). These patients were
      compared with 91 sex-and age-matched patients without aortic stenosis who
      underwent transesophageal echocardiography for various indications. Aortic
      atheroma was defined as localized intimal thickening of 3 mm or larger. A lesion
      was considered complex if there was a plaque extending 5 mm or more into the
      aortic lumen; if the lesion was protruding, mobile, or ulcerated; or both.
      RESULTS: The aortic stenosis group had significantly higher rates of aortic
      atheromas (85% vs 37%, P < .001) and complex atheromas (47% vs 9%, P < .001)
      compared with the control group. In the vast majority of patients in the aortic
      stenosis group, the aortic atheromas were localized in the aortic arch (60 [66%]
      patients, with 50% being complex aortic atheromas) and in the descending aorta
      (70 [77%] patients, with 45.7% being complex aortic atheromas); in only 4 (4.4%)
      patients, the aortic atheromas were localized in the ascending aorta (50% complex
      aortic atheromas). CONCLUSIONS: There is a strong association between the
      presence of severe aortic stenosis and the presence and severity of aortic
      atheromas, suggesting that aortic stenosis might be a manifestation of the
      atherosclerotic process. These findings imply that (1) aggressive atherosclerotic
      risk-factor modification for patients with aortic stenosis might be advisable and
      (2) consideration of evaluation of the aorta by means of transesophageal
      echocardiography before aortic valve replacement in selected patients might be
      helpful.

PMID- 15999038
TI  - Acute hemodynamic effects of restrictive mitral annuloplasty in patients with end
      stage heart failure: analysis by pressure-volume relations.
AB  - OBJECTIVE: Recent studies show beneficial long-term effects of restrictive mitral
      annuloplasty in patients with end-stage heart failure. However, concerns are
      raised about possible adverse effects on early postoperative systolic and
      diastolic function, which might limit application of this approach in patients
      with heart failure. Therefore we evaluated the acute effects of restrictive
      mitral annuloplasty on left ventricular function by using load-independent
      pressure-volume relations. METHODS: In 23 patients (heart failure, n = 10;
      control, n = 13) we determined left ventricular systolic and diastolic function
      before and after surgical intervention by means of pressure-volume analysis with
      a conductance catheter. All patients with heart failure underwent stringent
      restrictive mitral annuloplasty (2 sizes smaller than the measured size), and 4
      received additional coronary artery bypass grafting. Transesophageal
      echocardiography was used for evaluation of valve repair. Patients with preserved
      left ventricular function who underwent isolated coronary artery bypass grafting
      served as control subjects. RESULTS: Restrictive mitral annuloplasty (ring size,
      25 +/- 1) restored leaflet coaptation (8.0 +/- 0.2 mm) with normal pressure
      gradients (2.9 +/- 1.8 mm Hg). Restrictive mitral annuloplasty did not change
      cardiac output (5.0 +/- 1.8 to 5.3 +/- 0.9 L/min, P = .516), left ventricular
      ejection fraction (29% +/- 5% to 32% +/- 8%, P = .315), or end-systolic elastance
      (0.86 +/- 0.50 to 0.99 +/- 1.05 mm Hg/mL, P = .688). After restrictive mitral
      annuloplasty, end-diastolic volume tended to decrease (237 +/- 89 to 226 +/- 52
      mL, P = .564), whereas end-diastolic pressure remained unchanged (14 +/- 6 to 15
      +/- 5 mm Hg, P = .356). Diastolic chamber stiffness tended to increase (0.027 +/-
      0.035 to 0.041 +/- 0.047 mL -1 , P = .542) but not significantly. Peak left
      ventricular wall stress was unchanged (356 +/- 91 to 346 +/- 85 mm Hg, P = .668).
      Baseline values in the control group were different, but changes in most
      parameters after surgical intervention showed similar nonsignificant trends.
      CONCLUSION: Mitral valve repair by means of restrictive mitral annuloplasty
      effectively restores mitral valve competence without inducing significant acute
      changes in left ventricular systolic or diastolic function in patients with end
      stage heart failure.

PMID- 15999039
TI  - Three-dimensional in vivo characterization of calcification in native valves and
      in Freestyle versus homograft aortic valves.
AB  - OBJECTIVE: This article describes a novel interactive method for quantitative
      evaluation of calcium deposits in the aortic valve by means of electron beam
      tomography data fusion technique. METHODS: The technique relied on the use of
      hierarchic 3-dimensional free-form volume registration with fast global
      optimization between normally acquired and contrast-enhanced electron beam
      tomographic volume. A total of 66 contrast-enhanced electron beam tomographic
      scans of the aortic root were performed in 27 patients, 10 with native aortic
      valve disease (group A) and 17 from a prospective randomized trial of aortic root
      replacement (group B, 9 Freestyle grafts [Medtronic, Inc, Minneapolis, Minn] and
      8 homografts). To validate the in vivo electron beam tomographic measurements, 5
      patients from group A underwent electron beam tomographic scans before the
      operation and then had their own valves, explanted at the time of surgery,
      analyzed for calcium quantification by ex vivo electron beam tomography. RESULTS:
      In group A, the mean (+/- SE) calcification score was 6560 +/- 2388, which
      correlated with peak gradients measured at echocardiography ( r = 0.93, P = .02).
      In group B, the mean (+/- SE) calcification score was 168 +/- 27, showing a
      tendency toward a lower calcification for Freestyle valves than for homografts at
      2 years after implantation ( P = .052). A mean variability of 6% was found
      between in vivo electron beam tomographic scores of calcification and those
      measured on valve specimens after explantation. CONCLUSION: We describe a novel
      method to characterize the degree and location of calcification in both native
      valves and postoperative valve implants. The technique may be useful in the
      management of patients with aortic valve disease and has potential as a screening
      tool for high-risk patients to diagnose early valve calcification and possibly
      institute corrective measures.

PMID- 15999040
TI  - Congenital and surgically acquired Wolff-Parkinson-White syndrome in patients
      with tricuspid atresia.
AB  - OBJECTIVES: There are reports associating an increased incidence of Wolff
      Parkinson-White syndrome with tricuspid atresia. Here we report on
      electrophysiologic studies in patients with tricuspid atresia and Wolff-Parkinson
      White syndrome after the Fontan operation. In these patients the atrial
      arrhythmia often seen in patients undergoing the Fontan operation triggered
      atrioventricular re-entrant tachycardia or caused life-threatening arrhythmias.
      METHODS: Five patients with tricuspid atresia after palliation with a modified
      Fontan operation (atrioinfundibular connections) and Wolff-Parkinson-White
      syndrome are presented. RESULTS: Four of these patients had symptomatic
      paroxysmal orthodromic atrioventricular re-entrant tachycardia and a history of
      syncope; one of them additionally had atrial flutter with 2:1 conduction to the
      ventricle. A fifth patient presented with a life-threatening broad-complex
      tachycardia. In electrophysiologic studies an accessory pathway was localized in
      the right septal area in 3 patients. In 2 patients the accessory atrioventricular
      pathways were created by means of surgical intervention, connecting the right
      atrial appendage to the right ventricular outflow tract. All patients could be
      managed successfully by means of catheter ablation. CONCLUSIONS: In patients with
      tricuspid atresia, there are congenital and surgically acquired accessory
      pathways responsible for the increased rate of Wolff-Parkinson-White syndrome.
      Both types of accessory pathways can and should be treated by means of catheter
      ablation because atrial arrhythmia often seen in patients undergoing the Fontan
      operation can trigger atrioventricular re-entrant tachycardia or cause life
      threatening tachycardia. Congenital accessory pathways should be excluded
      carefully before surgical intervention for total cavopulmonary anastomosis in
      patients with tricuspid atresia.

PMID- 15999041
TI  - Monocyte function-associated antigen expression during and after pediatric
      cardiac surgery.
AB  - OBJECTIVE: Systemic inflammatory response syndrome and infectious complications
      are major causes of morbidity and mortality after cardiopulmonary bypass. Recent
      work in adult patients suggests that the balance between proinflammatory and anti
      inflammatory mediators is important. We hypothesized that the expression of
      different function-related receptors on circulating monocytes might reflect the
      net response of the inflammatory reaction. METHODS: We performed a prospective
      and observational study in a tertiary pediatric cardiac center in a population of
      children (n = 40) undergoing elective cardiac surgery. Expression of receptors on
      the surface of monocytes was assessed before, during, and after surgical
      intervention. RESULTS: Early monocyte activation was demonstrated by changes of
      the expression of the chemokine receptor CCR2, which was inversely correlated
      with plasma levels of monocyte chemotactic protein 1 (rho = -0.54, P = .002).
      High levels of monocyte chemotactic protein 1 were found in children with high
      expression of the adhesion receptor CD11b/CD18 on circulating monocytes. The
      intensity of human leukocyte antigen DR expression rapidly decreased in all
      children after the onset of cardiopulmonary bypass ( P < .001). Low human
      leukocyte antigen DR expression was correlated with increased plasma levels of
      interleukin 10 postoperatively. Children who had signs of bacterial pneumonia
      postoperatively had lower levels of human leukocyte antigen DR expression before
      surgical intervention (relative risk, 13.3; P = .007). CONCLUSIONS: The
      expression of monocyte function-related receptors is altered after cardiac
      surgery. Early activation of monocytes by monocyte chemotactic protein 1 possibly
      released from the heart is followed by an anti-inflammatory response with
      suppression of monocyte human leukocyte antigen DR expression. The increased risk
      of bacterial infection after pediatric cardiac surgery can be anticipated by
      surveillance of monocyte function before surgical intervention.

PMID- 15999042
TI  - Interdigitating arch reconstruction eliminates recurrent coarctation after the
      Norwood procedure.
AB  - BACKGROUND: We sought to determine whether evolving techniques of aortic arch
      reconstruction used during the Norwood procedure decreased the incidence of
      postoperative aortic arch obstruction. METHODS: Our technique for aortic arch
      reconstruction in patients undergoing the Norwood procedure has evolved from
      using an allograft patch (classic group, n = 26) to primary connection of the
      pulmonary artery and arch (autologous group, n = 20). More recently, we have used
      a novel technique involving coarctation excision, an extended end-to-end
      anastomosis on the back of the arch, and a counterincision on the anterior
      descending aorta to sew in an allograft patch for total arch reconstruction
      (interdigitating group, n = 33). Cardiac catheterizations performed before stage
      II palliation were reviewed for aortic diameters at multiple levels in 79 infants
      (median age, 4.2 months). Aortic arch obstruction was defined as a ratio between
      the diameters of the arch anastomosis and the descending aorta (coarctation
      index) of less than 0.7. RESULTS: Overall, 15 (19%) children had aortic arch
      obstruction. All 15 required aortic intervention (balloon angioplasty, n = 12;
      surgical patch angioplasty, n = 2; both, n = 1). Aortic arch obstruction rates
      for the classic, autologous, and interdigitating groups were 46% (n = 12), 15% (n
      = 3), and 0%, respectively ( P > .001). CONCLUSION: Reconstruction of the aortic
      arch with excision of ductal and coarctation tissue is associated with lower
      aortic arch obstruction rates in patients undergoing the Norwood procedure. Arch
      reconstruction with a novel interdigitating technique decreases the incidence of
      aortic arch obstruction.

PMID- 15999043
TI  - Mitral valve reconstruction in a pediatric population: late clinical results and
      predictors of long-term outcome.
AB  - OBJECTIVE: Pediatric mitral valve anomalies present complex management challenges
      to the surgeon, who may have to choose between valve replacement or repair. We
      review our 18 years of experience to establish the long-term outcomes of
      pediatric mitral repair. METHODS: Forty-five children (22 boys) with mitral valve
      anomalies were studied. Mitral reconstruction was performed in all cases at the
      first instance. The median age at operation was 2.16 years with 18 (40%) younger
      than 1 year. Patients were divided into two groups: group 1, isolated (mitral
      anomaly with or without atrial septal defect or patent ductus arteriosus),
      contained 30 patients (66.6%), and group 2, complex (mitral anomaly with
      concurrent intracardiac disease), contained 15 patients (33.3%). RESULTS: In
      hospital (30-day) mortality in group 1 was 3.3% (1/30); overall in-hospital
      mortality was 11.1%. Group 2 had a significantly higher in-hospital death rate of
      26.6% (4/15; P < .05). There was 1 late death, that of a child who required
      reoperation. The median follow-up was 5.08 years (range 1-211 months). The 15
      year survival in group 1 was 93%, versus 73% in group 2. Seven patients required
      9 revision surgical procedures. Two mitral valve replacements were required at
      reoperation. The 15-year freedom from reoperation was 81.7%. There were no
      thromboembolic events. The event-free rate at 15 years was 73.5%. CONCLUSION:
      This series compares favorably with others, with 74% to 85% survival and 66% to
      85.7% freedom from reoperation reported with valve replacement. Patients with
      significant associated congenital cardiac abnormalities are at a higher risk of
      early death after mitral reconstructive surgery.

PMID- 15999044
TI  - Optimal temperature for selective cerebral perfusion.
AB  - OBJECTIVE: Although combinations of hypothermic circulatory arrest and antegrade
      selective cerebral perfusion are used for cerebral protection during arch
      surgery, there is no consensus regarding the optimal temperature during selective
      cerebral perfusion. This study explored the effect of different temperatures
      during selective cerebral perfusion on cerebral metabolism and neurologic
      outcome. METHODS: In this blinded study, 40 pigs (19-21 kg) were randomized into
      4 groups after 30 minutes of hypothermic circulatory arrest at 20 degrees C.
      During a 60-minute interval of selective cerebral perfusion, with flow regulated
      to maintain a perfusion pressure of 50 mm Hg, pigs were perfused at 10 degrees C,
      15 degrees C, 20 degrees C, and 25 degrees C. Fluorescent microspheres enabled
      calculation of cerebral blood flow during perfusion and recovery. Hemodynamics,
      intracranial pressure, cerebrovascular resistance, and oxygen consumption were
      also monitored. Behavioral scores were obtained for 7 days after surgery.
      RESULTS: Cerebral blood flow decreased significantly ( P < .002) during cooling
      in all groups: it was significantly higher throughout selective cerebral
      perfusion in the 20 degrees C to 25 degrees C versus the 10 degrees C to 15
      degrees C group ( P = .0001) and remained higher during recovery ( P = .0001).
      Oxygen consumption decreased significantly with cooling ( P = .0001), remained
      low during perfusion, and rebounded with rewarming but was significantly lower at
      10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C throughout
      selective cerebral perfusion ( P = .003) and after CPB was discontinued ( P =
      .001). Postoperative behavioral scores were significantly better after selective
      cerebral perfusion at 10 degrees C to 15 degrees C than at 20 degrees C to 25
      degrees C ( P = .001). CONCLUSIONS: This study suggests that selective cerebral
      perfusion at 10 degrees C to 15 degrees C provides better cerebral protection
      than selective cerebral perfusion at 20 degrees C to 25 degrees C, even though
      oxygen consumption remains low for hours after selective cerebral perfusion at 10
      degrees C to 15 degrees C. Prompt return of metabolism to baseline levels after
      hypothermic circulatory arrest/selective cerebral perfusion does not necessarily
      predict superior behavioral outcome.

PMID- 15999045
TI  - Inhaled but not intravenous milrinone prevents pulmonary endothelial dysfunction
      after cardiopulmonary bypass.
AB  - OBJECTIVE: Cardiopulmonary bypass triggers a systemic inflammatory response that
      alters pulmonary endothelial function, which can contribute to pulmonary
      hypertension. Milrinone is a type III phosphodiesterase inhibitor. The objective
      of this study was to compare the effects of inhaled and intravenous milrinone on
      the pulmonary endothelium-dependent relaxations and hemodynamic and oxygenation
      parameters after cardiopulmonary bypass in a porcine model. METHODS: Five groups
      of Landrace swine were compared: (1) control group, no cardiopulmonary bypass;
      (2) bypass group, 90 minutes of normothermic bypass and 60 minutes of
      reperfusion; (3) inhaled milrinone group, bypass preceded by a 1.8-mg bolus of
      inhaled milrinone followed by a continuous milrinone nebulization; (4)
      intravenous milrinone group, bypass preceded by 2 mg of intravenous milrinone;
      and (5) inhaled NaCl group, bypass preceded by inhaled saline solution. After
      sacrifice, pulmonary arterial endothelium-dependent relaxations to acetylcholine
      and bradykinin were studied in organ chambers. RESULTS: Inhaled milrinone caused
      less hypotension ( P < .05), a lesser decrease in peripheral vascular resistances
      ( P < .01), and a lower heart rate ( P < .05) than intravenous milrinone. Inhaled
      milrinone prevented the alterations in relaxations of pulmonary arteries to
      acetylcholine caused by cardiopulmonary bypass, and relaxations to bradykinin
      were improved in the inhaled milrinone group ( P < .05) compared with the
      cardiopulmonary bypass and control groups. CONCLUSIONS: Inhaled milrinone
      prevents the occurrence of the pulmonary endothelial dysfunction seen after
      cardiopulmonary bypass. The hemodynamic and oxygenation profiles obtained with
      inhaled milrinone are safer than with intravenous milrinone. These strategies
      might be useful in preventing pulmonary hypertension after cardiac surgery.

PMID- 15999046
TI  - The effects of steroids on the occurrence of postoperative atrial fibrillation
      after coronary artery bypass grafting surgery: a prospective randomized trial.
AB  - OBJECTIVE: Atrial fibrillation remains one of the most common postoperative
      complications of coronary artery bypass grafting. Despite many clinical studies,
      there is still no consensus regarding the best prevention strategy for atrial
      arrhythmia. A randomized, double-blind, placebo-controlled trial was conducted to
      determine the effect of steroids on the occurrence of atrial fibrillation after
      elective coronary artery bypass grafting. METHODS: Eighty-eight consecutive
      patients were prospectively entered in this study. No patient had documented or
      suspected arrhythmias before surgery. Forty-three patients received 1 g of
      methylprednisolone before surgery and 4 mg of dexamethasone every 6 hours for 1
      day after surgery, and 43 patients received only placebo. The primary end point
      was the overall occurrence of postoperative atrial fibrillation. RESULTS:
      Postoperative atrial fibrillation occurred in 9 (21%) of the 43 patients in the
      steroid group, as compared with 22 (51%) of the 43 patients in the placebo group
      ( P = .003). Minor postoperative complications occurred in 15 steroid patients
      (35%) and in 6 patients (14%) receiving placebo ( P = .01). Major complications
      occurred in 4 patients who received steroids (9%) and in 2 patients (5%) who
      received placebo ( P = .68; for all complications, P = .05). CONCLUSIONS:
      Prophylactic short-term steroid administration in patients undergoing coronary
      artery bypass grafting significantly reduced postoperative atrial fibrillation.
      In this study, there was no significant difference between the steroid group and
      the placebo group with regard to the length of hospital stay; however, the
      steroid group had more complications, which may contribute to prolonged
      hospitalization.

PMID- 15999047
TI  - Reloading the heart: a new animal model of left ventricular assist device
      removal.
AB  - OBJECTIVES: Left ventricular assist devices are proposed as a bridge to recovery,
      but recurrent ventricular deterioration has limited this approach. We describe a
      new animal model that simulates the effects of left ventricular assist device
      unloading and then reloading after device removal. The model might facilitate the
      evaluation of interventions intended to prevent recurrent ventricular
      dysfunction. METHODS: The hearts and lungs of Lewis rats were removed and
      transplanted into the abdomen of recipient rats by anastomosing the donor's
      ascending aorta to the recipient's abdominal aorta. The transplanted hearts were
      maintained unloaded for 2 weeks in 49 animals. Eighteen transplanted hearts were
      removed after 2 weeks of unloading. In 17 animals the donor's right pulmonary
      artery was anastomosed to the recipient's abdominal aorta to reload the heart for
      an additional 2 weeks. In 14 animals the hearts were maintained unloaded for 4
      weeks (an additional 2 weeks). The unloaded and reloaded hearts were compared
      with normal rat hearts (n = 18). RESULTS: In the unloaded hearts the left
      ventricular end-diastolic pressures remained low. The left ventricular systolic
      pressures were lower than the aortic pressures. The left ventricular weights (n =
      8) and volumes (n = 4) remained significantly lower ( P < .01) than in the normal
      hearts. Two weeks after reloading, the left ventricular end-diastolic pressure (n
      = 8) increased ( P < .01), and the ventricle ejected. The left ventricular
      systolic pressures exceeded the aortic pressures. The left ventricular weights
      and volumes increased ( P < .01) and approached those of normal hearts. Matrix
      metalloproteinase 9 (n = 6/group) levels decreased in the unloaded state ( P =
      .02) and increased back to normal values after reloading. CONCLUSIONS: This
      surgical model simulated left ventricular assist device unloading of the left
      ventricle. The second operation reloaded the left ventricle, which then enlarged.
      This model will permit the evaluation of adjunctive interventions, such as cell
      transplantation, intended to facilitate successful left ventricular assist device
      removal and prevent recurrent dilatation.

PMID- 15999048
TI  - Recombinant human antithrombin III restores heparin responsiveness and decreases
      activation of coagulation in heparin-resistant patients during cardiopulmonary
      bypass.
AB  - OBJECTIVES: We sought to evaluate the efficacy of recombinant human antithrombin
      III for restoration of heparin responsiveness in heparin-resistant patients
      scheduled for cardiac surgery. METHODS: This was a multicenter, randomized,
      double-blind, placebo-controlled study in heparin-resistant patients undergoing
      elective cardiac surgery. Patients were considered heparin resistant if the
      activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty
      two heparin-resistant patients were randomized into 2 cohorts. One cohort
      received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28),
      and the other, the placebo group (n = 24), received a normal saline bolus. If the
      activated clotting time remained less than 480 seconds, this was defined as
      treatment failure, and 2 units of fresh frozen plasma were transfused. Patients
      were monitored for adverse events during hospitalization. RESULTS: Six (21%) of
      the patients in the recombinant human antithrombin III group received fresh
      frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients
      ( P < .001). Two units of fresh frozen plasma did not restore heparin
      responsiveness. There was no increased incidence of adverse events associated
      with recombinant human antithrombin III administration. Postoperative 24-hour
      chest tube bleeding was not different in the 2 groups. Surrogate measures of
      hemostatic activation suggested that there was less activation of the hemostatic
      system during cardiopulmonary bypass in the recombinant human antithrombin III
      group. CONCLUSION: Treatment with recombinant human antithrombin III in a dose of
      75 U/kg is effective in restoring heparin responsiveness and promoting
      therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin
      resistant patients. Two units of fresh frozen plasma were insufficient to restore
      heparin responsiveness. There was no apparent increase in bleeding associated
      with recombinant human antithrombin III.

PMID- 15999049
TI  - Acute effects of suction retraction on atrial hemodynamics and histology.
AB  - OBJECTIVES: In minimally invasive and robotic mitral valve surgery, a blade
      retractor is used to elevate the left atrial roof, which often distorts tissue
      and impairs visualization. We tested the hemodynamic and histologic changes of
      intra-atrial suction, using a new suction retractor that may improve
      stabilization and visualization. METHODS: Swine were divided into 3 equal (n = 4)
      groups: blade retractor, suction retractor, and arrested heart control. Left
      atrial ultrasonic crystals were used to record ejection fractions. After
      cardioplegic arrest, the atrium was opened and sampled for preretractor
      histology. Retractors remained in place for 1 hour, followed by postretractor
      histologic sampling. Controls were crossclamped for an equivalent time and
      postarrest histologic data obtained. Animals were weaned from bypass, data were
      collected for 4 hours, and postsacrifice atrial histologic samples were obtained.
      RESULTS: The main effect due to treatment was not statistically significant ( P =
      .52) between the 3 groups, with the 4-hour average ejection fraction for blade
      retractor, suction retractor, and control being statistically equivalent at 33.3%
      +/- 8.3, 35.3% +/- 12.1, and 40.8% +/- 9.9 (mean +/- standard deviation),
      respectively. Histology showed equivalent amounts of myocyte fragmentation,
      interstitial edema, eosinophilia, and wavy fibers between blade retraction and
      suction retraction, while the latter showed slightly increased amounts of
      hemorrhage. CONCLUSIONS: Atrial endocardial suction retraction appears to be safe
      with no acute changes in the left atrial ejection fraction or significant acute
      histologic differences, compared to blade retraction. Furthermore, intra-atrial
      suction may be applicable to procedures other than minimally invasive and robotic
      mitral valve repair for providing improved stabilization.

PMID- 15999050
TI  - Totally endoscopic robot-assisted transmyocardial revascularization.
AB  - OBJECTIVE: Laser transmyocardial revascularization is an emerging therapy for
      intractable angina stemming from diffuse, small-vessel coronary disease not
      amenable to percutaneous coronary intervention or coronary bypass grafting.
      Presently, this therapy is delivered through a median sternotomy or left
      thoracotomy. In this pilot study, we sought to combine the advantages of a
      dexterous robotic surgical platform with a flexible fiberoptic laser to develop a
      minimally invasive approach toward transmyocardial revascularization. METHODS: A
      flexible fiberoptic holmium:yttrium-aluminum-garnet laser probe (CardioGenesis
      Corporation, Foothill Ranch, Calif), deployed with the da Vinci surgical robotic
      system (Intuitive Surgical, Sunnyvale, Calif), was used to create transmyocardial
      channels through all left ventricular wall regions in 5 canine subjects. The
      channels were localized, quantified, and histologically analyzed to assess
      distribution, dimensions, and transmurality. RESULTS: Transmyocardial channels
      were successfully created in all 6 defined left ventricular wall segments by
      using this minimally invasive approach without port repositioning, instrument
      exchange, or probe modifications. Gross pathologic and histologic analyses
      confirmed the uniform distribution of 1.0-mm transmural channels in all left
      ventricular regions. No direct pressure, topical hemostatic agents, or suture
      repairs were required for hemostasis. No significant hemodynamic instability or
      sustained arrhythmias were encountered at any time during the procedures.
      CONCLUSIONS: We report the first use of a prototype flexible fiberoptic laser
      probe deployed by the da Vinci surgical robotic system to successfully perform
      totally endoscopic off-pump transmyocardial revascularization in a canine model,
      demonstrating the feasibility, precision, and safety of this approach. Refinement
      of this minimally invasive technique may reduce the morbidity of open-chest
      transmyocardial revascularization and facilitate its use as sole therapy or as an
      adjunct to percutaneous coronary interventions.

PMID- 15999051
TI  - Combination chemotherapy with gemcitabine with isolated lung perfusion for the
      treatment of pulmonary metastases.
AB  - OBJECTIVE: Isolated lung perfusion is an experimental technique for the treatment
      of lung metastases. Single-agent isolated lung perfusion does not result in
      complete remission. We studied the in vivo and in vitro efficacy of combinations
      of gemcitabine, cisplatin, and melphalan. METHODS: In vitro, using the
      sulforhodamine B assay, CC531s cells were incubated with cisplatin, gemcitabine,
      or melphalan or with a combination of these drugs. One drug was added at
      concentrations causing 25% growth inhibition, whereas the second drug was added
      at variable concentrations. In vivo, left pulmonary metastases were induced in
      Wag/Rij rats by means of intravenous injection of CC531s adenocarcinoma cells. At
      day 7, rats underwent left isolated lung perfusion with gemcitabine (n = 7),
      cisplatin (n = 9), melphalan (n = 7), gemcitabine-cisplatin (n = 6), melphalan
      gemcitabine (n = 6), and cisplatin-melphalan (n = 7). Death by means of
      metastatic disease was the end point. Survival and differences in survival were
      assessed by using Kaplan-Meier and log-rank testing. RESULTS: In vitro
      synergistic activity was observed for melphalan-gemcitabine, whereas other
      combinations showed additive or antagonistic activity. In vivo treated rats lived
      longer compared with control animals ( P < .0001). In isolated lung perfusion
      melphalan resulted in longer survival compared with gemcitabine ( P = .0016) and
      cisplatin ( P = .046). Isolated lung perfusion with melphalan-gemcitabine
      resulted in 67% survival of the rats after 90 days versus 0% in other groups.
      CONCLUSIONS: Isolated lung perfusion monotherapy or combination therapy with
      gemcitabine, cisplatin, or melphalan resulted in significantly longer survival
      compared with that seen in control animals. Isolated lung perfusion combination
      therapy with melphalan-gemcitabine resulted in the best survival either in vitro
      or in vivo.

PMID- 15999052
TI  - Decision-making for lung resection in patients with empyema and collapsed lung
      due to tuberculosis.
AB  - OBJECTIVE: Collapsed lung with associated empyema is a different clinical entity
      from destroyed lung . A low perfusion rate of the diseased lung is usually
      considered an indication for pneumonectomy in patients undergoing thoracotomy for
      tuberculosis. Such a criterion may not adequately reflect the functional capacity
      of the underlying parenchyma when the lung is collapsed. METHODS: One hundred
      twenty-seven patients underwent thoracotomy for tuberculosis at our hospital
      between 1998 and 2003. Among these, 5 (4%) patients who had a collapsed lung for
      more than 3 months and pleural infection were the subjects of this study. Surgery
      was considered after at least a 3-month course of regular antituberculous
      treatment. Despite no perfusions in 2 patients and 8%, 10%, and 15% perfusion
      rates for the remaining 3 patients, decortication alone was intentionally
      performed, and any kind of resectional operation was avoided. RESULTS: The lung
      gradually filled the hemithorax between 5 and 12 days after surgery in 4
      patients. The remaining patient required a thoracomyoplasty 8 weeks after the
      initial operation. Repeated perfusion scans 1 and 2 years after decortication
      continued to show no perfusion in patients who had had no preoperative perfusion.
      All patients were symptom free on regular follow-up between 10 months and 4.5
      years. CONCLUSIONS: It seems that the outcome is unpredictable in terms of lung
      expansion after decortication, which is a relatively simple procedure compared
      with other surgical options. We think that the risk of rethoracotomy is
      acceptable, considering the devastating complications and high mortality rates of
      resectional surgery in the treatment of such patients.

PMID- 15999053
TI  - Surgical treatment of solitary adrenal metastasis from non-small cell lung
      cancer.
AB  - BACKGROUND: Management of solitary adrenal metastasis from non-small cell lung
      cancer is still debated. Although classically considered incurable, various
      reports with small numbers of patients have shown that surgical treatment might
      improve long-term survival. The aim of this study was to review our experience
      and to identify factors that could affect survival. METHODS: From January 1989
      through April 2003, 23 patients underwent complete resection of an isolated
      adrenal metastasis after surgical treatment of non-small cell lung cancer. There
      were 19 men and 4 women, with a mean age of 54 +/- 10 years. The diagnosis of
      adrenal metastasis was synchronous with the diagnosis of non-small cell lung
      cancer in 6 patients and metachronous in 17 patients. The median disease-free
      interval for patients with metachronous metastasis was 12.5 months (range, 4.5
      60.1 months). RESULTS: The overall 5-year survival was 23.3%. Univariate and
      multivariate analysis demonstrated that a disease-free interval of greater than 6
      months was an independent and significant predictor of increased survival in
      patients after adrenalectomy. All patients with a disease-free interval of less
      than 6 months died within 2 years of the operation. The 5-year survival was 38%
      after resection of an isolated adrenal metastasis that occurred more than 6
      months after lung resection. Adjuvant therapy and pathologic staging of non-small
      cell lung cancer did not affect survival. CONCLUSIONS: Surgical resection of
      metachronous isolated adrenal metastasis with a disease-free interval of greater
      than 6 months can provide long-term survival in patients previously undergoing
      complete resection of the primary non-small cell lung cancer.

PMID- 15999054
TI  - The morphology of diaphragmatic defects in hepatic hydrothorax: thoracoscopic
      finding.
AB  - BACKGROUND: Until now, the pathophysiology of hepatic hydrothorax has been moot.
      We discuss (on the basis of gross videothoracoscopy findings in 11 cases and the
      literature) the pathogenesis and clinical presentation of this complex condition.
      METHODS: We prospectively studied 11 patients (age, 31-73 years; 6 men and 5
      women) with refractory hepatic hydrothorax (Child-Pugh class B-C) who underwent
      thoracoscopic repair of diaphragmatic defects. The diaphragmatic defects were
      examined intraoperatively. RESULTS: The diaphragmatic defects stemming from
      hepatic hydrothorax were classified into 4 morphologic types: type I, no obvious
      defect (1 patient); type II, blebs lying on the diaphragm (4 patients); type III,
      broken defects (fenestrations) in the diaphragm (8 patients); and type IV,
      multiple gaps in the diaphragm (1 patient). The type of diaphragmatic defect did
      not correlate with the volume occupied by the pleural effusion in the
      preoperative chest radiograms. CONCLUSIONS: The finding of this study allowed
      hepatic hydrothorax pathophysiology to be directly visualized, and further
      studies concerning the treatment of hepatic hydrothorax might be based on these
      mechanisms.

PMID- 15999055
TI  - Treatment of airway obstruction by metallic stents in infants and children.
AB  - OBJECTIVE: The internal metallic stent is a relatively new and controversial
      method for the treatment of airway collapse in infants and children. The study
      examined the outcomes of this treatment in a large group of patients and defined
      clear indications for airway stenting. METHODS: A retrospective review was
      conducted of 32 patients in whom 42 stents were inserted. The patients were
      divided into three groups with respect to the stented segment: group A, trachea
      (n = 14); group B, bronchi (n = 16); and group C, trachea and bronchi (n = 2).
      RESULTS: In 30 cases, there was immediate improvement of respiratory obstruction,
      and 23 patients could be weaned, at least temporarily, from ventilation.
      Excessive granulation developed after the stenting in 26 patients. In 6 patients,
      all in group A, the granulation and inflammatory reaction generated severe airway
      obstruction, necessitating thoracotomy in 2 cases. One patient died of airway
      obstruction, and another died during the attempt to remove the stent; both were
      in group A. Stents placed for 2 to 72 months (mean 8.7 months) have now been
      removed in 11 patients. Six children are alive and well with stents in place, 2
      from group A and 4 from group B. Fifteen patients died during the follow-up
      period; in 13 cases, death was related to the associated disease. CONCLUSION: The
      use of metallic stents, especially in the trachea, is associated with a high rate
      of complications. Granulation tissue, which often develops after stenting, is a
      major concern. Removal of the stents is arduous and carries a high risk of
      complications. The use of stents should be restricted to the limited situations
      in which conventional initial therapy has failed.

PMID- 15999056
TI  - The maximum standardized uptake values on positron emission tomography of a non
      small cell lung cancer predict stage, recurrence, and survival.
AB  - OBJECTIVE: We sought to assess whether the standard uptake value of a pulmonary
      nodule is an independent predictor of biologic aggressiveness. METHODS: This is a
      retrospective review of a prospective database of patients with non-small cell
      lung cancer. Patients had dedicated positron emission tomography scanning with F
      18 fluorodeoxyglucose, with the maximum standard uptake value measured. All
      suspicious nodal and systemic locations on computed tomographic and positron
      emission tomographic scanning underwent biopsy, and when indicated, resection
      with complete lymphadenectomy was performed. RESULTS: There were 315 patients.
      Multivariate analysis showed patients with a high maximum standard uptake value
      (>/=10) were more likely to have poorly differentiated tumors (risk ratio, 1.5; P
      = .005) and advanced stage (risk ratio, 1.9; P = .010) and were less likely to
      have their disease completely resected (risk ratio, 3.7; P = .004). Maximum
      standard uptake value was the best predictor of disease-free survival (hazard
      ratio, 2.5; P = .039) and survival (hazard ratio, 2.8; P = .001). Stage-specific
      analysis showed that patients with stage IB and stage II disease with a maximum
      standard uptake value of greater than the median for their respective stages had
      a lower disease-free survival at 4 years ( P = .005 and .044). The actual 4-year
      survival for patients with stage Ib non-small cell lung cancer was 80% versus 66%
      ( P = .048), for stage II disease it was 64% versus 32% ( P = .028), and for
      stage IIIa disease it was 64% versus 16% ( P = .012) for the low and high maximum
      standard uptake value groups, respectively. CONCLUSIONS: The maximum standard
      uptake value of a non-small cell lung cancer nodule on dedicated positron
      emission tomography is an independent predictor of stage and tumor
      characteristics. It is a more powerful independent predictor than the TNM stage
      for recurrence and survival for patients with early-stage resected cancer. This
      information might help guide treatment strategies.

PMID- 15999058
TI  - Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung
      cancer.
AB  - OBJECTIVE: Large cell neuroendocrine carcinomas of the lung display morphologic
      and immunohistochemical characteristics common to neuroendocrine tumors and the
      morphologic features of large cell carcinomas. Surgical resection of large cell
      neuroendocrine carcinomas in many series has been described, with 5-year
      actuarial survivals ranging from 13% to 57%. Considerable debate has emerged as
      to whether these tumors should be classified and treated as non-small cell lung
      cancers or small cell lung cancers. The objective of this study was to report the
      outcome of surgical resection in patients with large cell neuroendocrine
      carcinomas. METHODS: An analysis of our tumor registry was performed to identify
      all patients undergoing surgical resection of lung cancer between July 1, 1988,
      and December 31, 2002, for large cell tumors. Cases were then segregated into
      large cell neuroendocrine carcinomas, mixed large cell neuroendocrine carcinomas
      (in which at least one portion of the tumor was a large cell neuroendocrine
      carcinoma), or large cell carcinomas on the basis of morphology and
      differentiation. Follow-up was complete on all patients, with a mean follow-up of
      48 months. Type of resection, mortality, and survival by stage were analyzed.
      Kaplan-Meier survival was determined for all patients from the date of surgical
      intervention. Cox proportional hazards model analysis incorporating the variables
      of age, sex, histology, and stage estimated the effect of large cell
      neuroendocrine carcinomas and mixed large cell neuroendocrine carcinomas on
      recurrence and death. The stage of disease in all patients was assessed according
      to the 1997 American Joint Committee on Cancer guidelines. RESULTS: Of the 2099
      patients who underwent resection, 82 (3.9%) had large cell lung cancers.
      Perioperative mortality was 2.4%. Overall survival and freedom from recurrence at
      5 years for the entire group was 47.1% and 58.4%, respectively. Overall survival
      by histologic subtype at 5 years was 30.2% for patients with large cell
      neuroendocrine carcinomas (n = 45), 30.3% for patients with mixed large cell
      neuroendocrine carcinomas (n = 11), and 71.3% for patients with large cell
      carcinomas (n = 21). Survival was significantly worse for patients with large
      cell neuroendocrine carcinomas than for patients with large cell carcinomas ( P =
      .013). The presence of large cell neuroendocrine carcinomas in the specimen (the
      large cell neuroendocrine carcinoma and mixed large cell neuroendocrine carcinoma
      groups combined) was significantly associated with decreased survival (relative
      risk, 2.44; 95% confidence interval 1.29-4.58; P = .003) and decreased freedom
      from recurrence (relative risk, 4.52; 95% confidence interval, 1.76-11.57; P <
      .001). CONCLUSION: Patients with large cell neuroendocrine carcinomas have a
      significantly worse survival after resection than patients with large cell
      carcinomas, even in stage I disease. Accurate differentiation of large cell
      neuroendocrine carcinoma from large cell carcinoma is important because it
      identifies those patients at highest risk for the development of recurrent lung
      cancer.

PMID- 15999057
TI  - Visceral pleural invasion is an invasive and aggressive indicator of non-small
      cell lung cancer.
AB  - OBJECTIVE: Although visceral pleural invasion by non-small cell lung cancer is
      considered a poor-prognostic factor, further information is lacking, especially
      in relation to other clinicopathologic prognostic factors. We assessed the
      relationship between visceral pleural invasion and other clinicopathologic
      characteristics and evaluated its significance as a prognostic factor. METHODS:
      We reviewed 1074 patients with surgically resected T1/2 non-small cell lung
      cancer for their clinicopathologic characteristics and prognoses. The patients
      were divided into 2 groups according to visceral pleural invasion status
      (visceral pleural invasion group and non-visceral pleural invasion group). Both
      groups were compared with regard to age, sex, histology, tumor size, tumor
      differentiation, lymph node involvement, lymphatic invasion, vascular invasion,
      scar grade, nuclear atypia, mitotic index, serum carcinoembryonic antigen level,
      and survival. Univariate and multivariate analyses were conducted. RESULTS:
      Visceral pleural invasion was identified in 288 (26.8%) of the resected
      specimens. Survival was 76.0% at 5 years and 53.2% at 10 years in the non
      visceral pleural invasion group and was 49.8% at 5 years and 37.0% at 10 years in
      the visceral pleural invasion group. The difference between groups was highly
      significant ( P < .0001). Visceral pleural invasion was also significantly
      associated with a higher frequency of lymph node involvement. However, regardless
      of N status (N0 or N1/2), there was a significant difference in survival when the
      visceral pleura was invaded. Visceral pleural invasion was observed significantly
      more frequently in tumors with factors indicative of tumor
      aggressiveness/invasiveness: moderate/poor differentiation, lymphatic invasion,
      vascular invasion, high scar grade, high nuclear atypia grade, high mitotic
      index, and high serum carcinoembryonic antigen level. By multivariate analysis,
      visceral pleural invasion proved to be a significant independent predictor of
      poor prognosis in non-small-cell lung cancer patients with or without lymph node
      involvement. CONCLUSIONS: Visceral pleural invasion is a significant poor
      prognostic factor, regardless of N status. Our analyses indicated that visceral
      pleural invasion is an independent indicator of non-small cell lung cancer
      invasiveness and aggressiveness.

PMID- 15999059
TI  - Enhancement of the functional benefits of skeletal myoblast transplantation by
      means of coadministration of hypoxia-inducible factor 1alpha.
AB  - OBJECTIVE: Early cell death remains a major limitation of skeletal myoblast
      transplantation. Because the poor vascularization of the target scars contributes
      to cell loss, we assessed the effects of combining skeletal myoblast
      transplantation with administration of hypoxia-inducible factor 1alpha, a master
      gene that controls the expression of a wide array of angiogenic factors. METHODS:
      A myocardial infarction was created in 56 rats by means of coronary artery
      ligation. Eight days later, rats were randomly allocated to receive in-scar
      injections of culture medium (control animals, n = 11), skeletal myoblasts (5 x
      10(6) , n = 13), adenovirus-encoded hypoxia-inducible factor 1alpha (1.0 x 10(10)
      pfu/mL, n = 7), or skeletal myoblasts (5 x 10(6)) in combination with an empty
      vector (n = 3) or active hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL, n
      = 13). A fifth group (n = 9) underwent a staged approach in which hypoxia
      inducible factor 1alpha (1.0 x 10(10) pfu/mL) was injected at the time of
      infarction, followed 8 days later by skeletal myoblasts (5 x 10(6)). Left
      ventricular function was assessed echocardiographically before transplantation
      and 1 month thereafter. Explanted hearts were then processed for the
      immunohistochemical detection of myotubes, quantification of angiogenesis,
      myoblast engraftment, and cell survival. RESULTS: Baseline ejection fractions
      were not significantly different among groups (35%-40%). One month later,
      ejection fraction had decreased from baseline in control hearts and in those
      injected with hypoxia-inducible factor 1alpha. In contrast, it did not
      deteriorate after injections of skeletal myoblasts alone or combined with either
      the empty vector or active hypoxia-inducible factor 1alpha administered
      sequentially. The most striking change occurred in the skeletal myoblast plus
      hypoxia-inducible factor 1alpha combined group in which ejection fraction
      increased dramatically (by 27%) above baseline levels and was thus markedly
      higher than in all other groups ( P = .0001 and P = .001 vs control animals and
      animals receiving hypoxia-inducible factor 1alpha, respectively). Compared with
      skeletal myoblasts alone, the coadministration of hypoxia-inducible factor 1alpha
      resulted in a significantly greater degree of angiogenesis, cell engraftment, and
      cell survival. CONCLUSION: Induction of angiogenesis is an effective means of
      potentiating the functional benefits of myoblast transplantation, and hypoxia
      inducible factor 1alpha can successfully achieve this goal.

PMID- 15999060
TI  - Evaluation of the oxygenation ratio in the definition of early graft dysfunction
      after lung transplantation.
AB  - OBJECTIVE: Despite the clinical importance of early graft dysfunction, no
      standardized definition is available. We hypothesized that the arterial blood gas
      oxygen tension/fraction of inspired oxygen ratio (PaO2 /FIO2) would prove to be a
      useful marker for predicting subsequent outcomes of early graft dysfunction. The
      aims of this study were to define the prevalence of various ranges of PaO2 /FIO2
      over the first 48 hours after lung transplantation and to evaluate which
      measurement using the PaO2 /FIO2 best correlates with the duration of intubation,
      the length of stay in the intensive care unit, and 30-day mortality, which are
      important alternative indicators of early graft performance. METHODS: A
      retrospective study was performed that included all 68 bilateral single-lung
      transplantations at The Alfred Hospital from January 2000 to December 2002.
      RESULTS: PaO2 /FIO2 at 6 and 12 hours after admission to the intensive care unit
      was significantly associated with the duration of intubation ( r = -0.44; P <
      .001 and r = -0.48; P < .001, respectively), and PaO2 /FIO2 at 6 and 24 hours was
      also significantly associated with the length of intensive care unit stay ( r = 
      0.38; P = .002 and r = -0.44; P = .001, respectively). Thirty-day mortality was
      significantly associated with a lower PaO2 /FIO2 at 6 hours (219 +/- 93 vs 306 +/
      101; P = .03). CONCLUSIONS: PaO2 /FIO2 taken between 6 and 12 hours after
      transplantation is a useful marker associated with lung transplantation outcomes.
      There is the potential for therapeutic interventions during this time that may be
      able to enhance PaO2 /FIO2 by 12 hours and improve subsequent outcomes.

PMID- 15999061
TI  - Does duration of donor brain injury affect outcome after orthotopic pediatric
      heart transplantation?
AB  - OBJECTIVE: We tested the hypothesis that duration of donor brain injury and death
      would have an adverse effect on recipient rejection and mortality in pediatric
      heart transplantation. METHODS: Ninety-three cardiac transplants were performed
      at our center from July 1, 1997, through June 30, 2003. The primary study end
      points were the number of rejection episodes and the time to first rejection.
      Secondary outcomes were early and late mortality. RESULTS: Among 88 recipients of
      93 cardiac allografts, 5 (6%) and 1 (1%) received second and third allografts,
      respectively. Overall patient mortality (3 early and 2 late) was 6% (5/88), and
      overall graft loss was 6% (6/93). Median time from donor brain injury to
      declaration of brain death (brain injury interval), time from brain death to
      donor cardiectomy (brain death interval), and graft ischemia time were 38, 24,
      and 3.3 hours, respectively. Cox regression analysis (adjusting for United
      Network for Organ Sharing status, ventilator dependence, extracorporeal membrane
      oxygenation and ventricular-assist device status, diagnosis of congenital heart
      disease, sex and cytomegalovirus mismatches, and type of immunosuppression)
      demonstrated that recipients of donor hearts with relatively long periods from
      brain injury to death declaration or from death to organ removal had
      significantly improved rejection-free survival (hazard ratios 0.3, P = .01, and
      0.5, P = .05, for brain injury and brain death times, respectively). Prolonged
      donor heart ischemia did not impact rejection rate. Increasing brain injury
      interval, brain death interval, and graft ischemia time had no significant effect
      on mortality. CONCLUSION: Longer brain injury and death intervals correlated with
      improved freedom from rejection but had no effect on mortality.

PMID- 15999062
TI  - Inhibition of nuclear factor kappaB by IkappaB superrepressor gene transfer
      ameliorates ischemia-reperfusion injury after experimental lung transplantation.
AB  - OBJECTIVES: Ischemia-reperfusion injury after lung transplantation is associated
      with significant morbidity and mortality. The activation of the transcription
      factor nuclear factor kappaB is central to the 2 important pathways that
      characterize ischemia-reperfusion injury, namely the inflammatory response and
      apoptosis. The purpose of this study was to determine the effects of nuclear
      factor kappaB inhibition on experimental lung transplant ischemia-reperfusion
      injury with gene transfer of the nuclear factor kappaB inhibitor IkappaB in a
      superrepressor form (IkappaBSR). METHODS: An orthotopic left lung transplant
      model in isogeneic rats was used, with 18 hours of prolonged cold storage of
      donor lung grafts used to create severe ischemia-reperfusion injury. Donor rats
      underwent endobronchial gene transfection with saline alone or adenovirus
      encoding either beta-galactosidase control or IkappaBSR 48 hours before harvest.
      The function of transplanted lung grafts was assessed on the basis of isolated
      graft oxygenation, wet/dry lung weight ratio, and myeloperoxidase activity.
      Nuclear factor kappaB activation was assessed by means of enzyme-linked
      immunosorbent assay. Apoptotic cell death was assessed by evaluating the levels
      of histone-associated DNA fragments and caspase-3 activity. RESULTS: Treatment of
      donor lung grafts with IkappaBSR resulted in significantly improved oxygenation
      compared with that seen in control tissue 24 hours after transplantation.
      IkappaBSR-treated lungs also demonstrated less pulmonary edema and reduced
      neutrophil infiltration 24 hours after reperfusion. Nuclear factor kappaB
      activation and apoptotic cell death induction 2 hours after transplantation was
      significantly reduced in IkappaBSR-treated lungs compared with in control lungs.
      CONCLUSIONS: Inhibition of nuclear factor kappaB activation by IkappaBSR gene
      transfer improves transplanted lung graft oxygenation, decreases pulmonary edema
      and neutrophil sequestration, and reduces apoptotic cell death after experimental
      lung transplantation.

PMID- 15999063
TI  - Clinical-pathologic conference in cardiac surgery: malignant schwannoma of the
      heart.

PMID- 15999064
TI  - Historical perspectives of The American Association for Thoracic Surgery: Emile
      Frederic Holman, MD (1890-1977).

PMID- 15999065
TI  - Giant pseudoaneurysm after proximal aortic surgery treated by means of redo
      axillary artery cannulation and use of an Endoclamp device.

PMID- 15999066
TI  - Successful removal of migrated acupuncture needles in a patient with cardiac
      tamponade by means of intraoperative transesophageal echocardiographic
      assistance.

PMID- 15999067
TI  - Ross procedure with a quadricuspid pulmonary autograft.

PMID- 15999068
TI  - Aortic root replacement in a patient with pulmonary dysfunction caused by severe
      chest deformity associated with Marfan syndrome.

PMID- 15999069
TI  - Embryologic and surgical considerations in tetralogy of Fallot with right arch
      and aberrant left subclavian artery from the ascending aorta.

PMID- 15999070
TI  - Functional classification dictates type of repair in "complex" mitral
      insufficiency: Application to a case of a hammock mitral valve in an adult
      patient.

PMID- 15999071
TI  - Left ventricular restoration for ischemic cardiomyopathy and simultaneous
      implantation of left ventricular assist system actively aiming at bridge to
      recovery.

PMID- 15999072
TI  - An alternative retractor for transcervical thymectomy.

PMID- 15999073
TI  - Multiple tracheal stenting or perseverare diabolicum est.

PMID- 15999074
TI  - Endovascular treatment of a combined pseudoaneurysm and arteriovenous fistula of
      the subclavian artery caused by a gunshot wound to the chest.

PMID- 15999075
TI  - Mediastinal-like growing teratoma syndrome.

PMID- 15999076
TI  - Thoracoscopic approach to the resection of an azygos vein aneurysm.

PMID- 15999077
TI  - Radial artery conduits in coronary artery bypass grafting: current perspective.

PMID- 15999078
TI  - Atrial fibrillation: isolation or ablation?

PMID- 15999079
TI  - Performance of surgery for congenital heart disease: shall we wait a generation
      or look for different statistics?

PMID- 15999081
TI  - Compliance with professional standards to enhance patient safety.

PMID- 15999082
TI  - Insurance reimbursement.

PMID- 15999083
TI  - More on reasonable accommodation.

PMID- 15999084
TI  - NCCAM herbal supplement studies underway in the United States.

PMID- 15999086
TI  - Medical errors 101: a primer.

PMID- 15999087
TI  - Ethically speaking: the case manager's response to harm-causing error.
AB  - The purpose of this article is to morally assess various reactions from internal
      and external case managers when they suspect or realize that their patient or
      client experienced a harm-causing medical error.

PMID- 15999088
TI  - Case managers' encounters with errors.
AB  - Case managers certainly come across or suspect medical errors. This article
      offers a glimpse into the variety of mishaps, possible errors, and even moral
      ambiguities connected with errors that a case manager may experience. The primary
      objective of the article is simply to give readers an idea of the kinds of error
      scenarios a case manager may encounter. The cases appearing here are taken from
      actual accounts.

PMID- 15999089
TI  - Case management and patient safety: opportunities for process and performance
      improvement.
AB  - Awareness and activities about patient safety and the need for improvement are
      wide-spread within the health care industry, but the role and the expectation for
      case management in this area has not yet been well defined. Some case managers
      voice doubts about the ability to affect safety because they typically are not
      direct caregivers. Is it realistic to expect case managers and their
      organizations to influence and improve patient safety?

PMID- 15999090
TI  - Patient safety.
AB  - Patient safety is a cause for concern among health care providers, payers,
      employers, policy makers, and the general public. But it is difficult for most
      case managers to get their arms around what they can do about patient safety in
      hospitals. This article discusses the patient safety movement in this country and
      defines the vital role case managers can play in making health care safer for
      patients. It describes the changing case manager challenges and competencies
      needed to meet these challenges.

PMID- 15999091
TI  - Identifying and reducing risk of medical errors.
AB  - From assessment and planning to evaluation and outcomes, case management is a
      proactive process that provides access to quality, safe, effective, and timely
      care. Each step in the case management process, especially when undertaken by a
      qualified professional provider, may also provide an added and significant
      benefit-the potential to reduce or to prevent the risk of medical errors.

PMID- 15999092
TI  - Using case management guidelines to enhance adherence to long-term therapy.

PMID- 15999093
TI  - New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions.
AB  - Understanding the factors that influence T helper 1 (T(H)1)- and T(H)2-cell
      responses has been one of the main focuses of immunology for almost 20 years.
      Whereas the central role of interleukin-12 (IL-12) in the generation of T(H)1
      cells has long been appreciated, subsequent studies indicated that IL-23 and IL
      27, two cytokines that are closely related to IL-12, also regulate T(H)1-cell
      responses. However, as discussed in this article, it is now recognized that the
      ability of IL-23 to stimulate a unique T-cell subset to produce IL-17 has a
      dominant role in autoimmune inflammation. By contrast, IL-27 has a role in
      limiting the intensity and duration of adaptive immune responses.

PMID- 15999094
TI  - Tuning immune responses: diversity and adaptation of the immunological synapse.
AB  - The onset and regulation of a specific immune response results from communication
      between T cells and antigen-presenting cells (APCs), which form molecular
      interactions at the site of cell-cell contact--and this is known as the
      immunological synapse. Initially, the immunological synapse was viewed as a
      stereotypical adhesion and signalling device with a defined molecular structure
      and signalling processes. However, as we discuss here, T-cell-APC interactions
      comprise a diverse range of contact modes and distinct molecular arrangements.
      These diverse interaction modes might define a molecular code, in which the
      differences in timing, spacing and molecular composition of the signalling
      platform determine the outcome of T-cell-APC interactions.

PMID- 15999095
TI  - Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network.
AB  - Sphingosine 1-phosphate (S1P) is a biologically active lysophospholipid that
      transmits signals through a family of G-protein-coupled receptors to control
      cellular differentiation and survival, as well as the vital functions of several
      types of immune cell. In this Review article, we discuss recent results that
      indicate that S1P and its receptors are required for the emigration of thymocytes
      from the thymus, the trafficking of lymphocytes in secondary lymphoid organs and
      the migration of B cells into splenic follicles. In an autocrine manner, through
      interactions with different G-protein-coupled receptors, S1P also enhances
      optimal mast-cell migration and release of pro-inflammatory mediators in allergic
      reactions. S1P-S1P-receptor regulatory systems might therefore be novel targets
      for the therapy of diverse immunological diseases.

PMID- 15999096
TI  - Unique features of the pre-T-cell receptor alpha-chain: not just a surrogate.
AB  - The pre-T-cell receptor (pre-TCR) has a crucial role in the normal development of
      alphabeta T cells. Different views have emerged concerning the structure and
      function of the pre-TCR. This molecular complex can be viewed as a variant of the
      alphabeta-TCR in which the pre-TCR alpha-chain that is covalently associated with
      the TCR beta-chain is a 'surrogate' TCR alpha-chain. Alternatively, the unique
      structure of the pre-TCR might be associated with a unique function, owing to
      evolutionary selection of a pre-TCR alpha-chain that has different capabilities
      from the TCR alpha-chain. As described here, I consider that experimental
      evidence favours the latter view.

PMID- 15999097
TI  - The pre-B-cell receptor: selector of fitting immunoglobulin heavy chains for the
      B-cell repertoire.
AB  - In this Opinion article, I address the role of the pre-B-cell receptor (pre-BCR)
      in the development of antigen-specific B cells in terms of immunoglobulin heavy
      chain (IgH) variable-region repertoire selection, precursor B-cell
      differentiation and proliferation, and IgH allelic exclusion. Comparisons with
      the role of the pre-T-cell receptor (pre-TCR) in T-cell development raise
      provocative questions. Why do B- and T-cell lineages both use a surrogate chain -
      the surrogate light chain and the pre-TCR alpha-chain, respectively - as a step
      to develop their repertoires of antigen-recognizing cells? What are the functions
      of the pre-BCR and pre-TCR in lymphocyte differentiation and antigen-receptor
      allelic exclusion? This article, together with the accompanying article by Harald
      von Boehmer, hopes to answer some of these questions.

PMID- 15999098
TI  - Serum CA19-9 response as a surrogate for clinical outcome in patients receiving
      fixed-dose rate gemcitabine for advanced pancreatic cancer.
AB  - The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to
      guide treatment decisions and serve as a surrogate end point in clinical trial
      design requires further validation. We investigated whether CA19-9 decline
      represents an accurate surrogate for survival and time to treatment failure (TTF)
      in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose
      rate gemcitabine in three separate studies. Statistically significant
      correlations between percentage CA19-9 decline and both overall survival and TTF
      were found, with median survival ranging from 12.0 months for patients with the
      greatest degree of biomarker decline (> 75%) compared with 4.3 months in those
      whose CA19-9 did not decline during therapy (P < 0.001). Using specific
      thresholds, patients with > or = 25% decline in CA19-9 during treatment had
      significantly better outcomes than those who did not (median survival and TTF of
      9.6 and 4.6 months vs 4.4 and 1.5 months; P < 0.001). Similar results were seen
      using both 50 and 75% as cutoff points. We conclude that serial CA19-9
      measurements correlate well with clinical outcomes in this patient population,
      and that decline in this biomarker should be entertained for possible use as a
      surrogate end point in clinical trials for the selection of new treatments in
      this disease.

PMID- 15999099
TI  - Assessing proliferation, cell-cycle arrest and apoptotic end points in human
      buccal punch biopsies for use as pharmacodynamic biomarkers in drug development.
AB  - Easily accessible normal tissues expressing the same molecular site(s) of drug
      action as malignant tissue offer an enhanced potential for early proof of
      anticancer drug mechanism and estimation of the biologically effective dose.
      Studies were undertaken in healthy male volunteers to assess the tolerability of
      single and multiple (four in 24 h) 3 mm punch biopsies of the buccal mucosa, and
      to determine the feasibility of detecting and quantifying a range of
      proliferation, cell-cycle arrest and apoptosis markers by immunohistochemistry
      (IHC) for use as potential pharmacodynamic (PD) end points. The biopsy procedure
      was well tolerated with 100% of volunteers stating that they would undergo single
      (n = 10) and multiple (n = 12) biopsies again. Total retinoblastoma protein
      (pRb), phosphorylated pRb (phospho-pRb), total p27, phosphorylated p27 (phospho
      p27), phosphorylated-histone H3 (phospho-HH3), p21, p53, Cyclin A, Cyclin E, Ki67
      all produced good signal detection, but M30, cleaved caspase 3 and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling did not.
      Total pRb, phospho-pRb, total p27 and phospho-p27 were quantified further in a
      multiple biopsy study to allow components of variability to be addressed to
      inform future sizing decisions on intervention studies. Neither site of biopsy
      within the oral cavity, nor the nominal time of biopsy had any significant impact
      on any of the four markers expression levels. Inter- and intrasubject
      coefficients of variation (CVs) that could be used to size future intervention
      studies for pRb, phospho-pRb, total p27 and phospho-p27 were 14, 19, 18 and 16%;
      and 18, 29, 25 and 19%, respectively. In conclusion, quantitation of such markers
      in 3 mm buccal punch biopsies would be suitable to explore as PD end points
      within intervention studies of drugs acting on these pathways.

PMID- 15999100
TI  - Correction of anaemia through the use of darbepoetin alfa improves
      chemotherapeutic outcome in a murine model of Lewis lung carcinoma.
AB  - Darbepoetin alfa (Aranesp), Amgen) is a novel erythropoiesis-stimulating protein
      with a serum half-life longer than recombinant human erythropoietin (Epo), used
      in the treatment of cancer-associated anaemia. Anaemia is known to adversely
      affect prognosis and response to treatment in cancer patients. Solid tumours
      contain regions of hypoxia due to poor vascular supply and cellular compaction.
      Although hypoxic stress usually results in cell death, hypoxia-resistant tumour
      cells are genetically unstable and often acquire a drug-resistant phenotype.
      Increasing tumour oxygenation and perfusion during treatment could have the
      doubly beneficial outcome of reducing the fraction of treatment-resistant cells,
      while increasing drug delivery to previously hypoxic tissue. In this study, we
      examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery
      in an in vivo model of Lewis lung carcinoma, shown here to express the Epo
      receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing
      10 days before chemotherapy, resulted in a significant reduction in tumour volume
      compared to chemotherapy alone. This was mediated by the prevention of anaemia, a
      reduction in tumour hypoxia and a concomitant increase in drug delivery.
      Darbepoetin alfa treatment alone did not modulate the growth of the EpoR
      expressing tumour cells. This study identifies an important role for darbepoetin
      alfa in increasing the therapeutic index of chemotherapy.

PMID- 15999101
TI  - p53 immunodetection of liquid-based processed urinary samples helps to identify
      bladder tumours with a higher risk of progression.
AB  - p53 could help identify bladder tumour cases with a risk of progression from
      superficial to invasive disease. Semiautomatic, liquid-based cytology (LBC)
      techniques offer an opportunity to standardise molecular techniques. The aim of
      our study was to investigate whether LBC could improve p53 immunolabelling, and
      to assess whether urinary p53 could have a prognostic value. Immunoreactivity for
      p53 was studied in 198 urine samples after treatment with the Cytyc Thinprep
      processor. After antigen retrieval, cells were labelled with a monoclonal
      antibody that recognises both wild-type and mutant form of the p53 protein (Clone
      DO-7, Dako), 1/1000. Positivity for p53 was assessed in 17.2% of the cases. High
      grade (G3) tumours were positive in 74.1% of the cases. Comparatively, low-grade
      (G1-2) urothelial carcinomas were positive in 23.5% of the cases. During a median
      follow-up period of 26 months, recurrence was observed in 52.9% of the cases with
      p53 overexpression, and in only 10.9% of negative cases (P < 0.001). The
      progression rate was 35.3% of p53-positive cases vs 5.5% of p53-negative cases (P
      < 0.001). Progression-free survival was significantly shorter in patients with
      p53 accumulation (P = 0.007). In a multivariate analysis stratified on grade and
      stage, p53 was an independent predictor of overall survival (P = 0.042). The
      results show that using Thinprep LBC, p53 immunolabelling of voided urothelial
      cells allows most high-grade tumours to be detected and may help identify cases
      with a higher risk of recurrence and progression.

PMID- 15999102
TI  - A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second
      line (post-BEP) salvage chemotherapy for patients with metastatic germ cell
      cancer: a medical research council trial.
AB  - This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide
      and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who
      have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy.
      Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy
      or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg
      m(-2) day 1, followed on days 1-5 by ifosfamide 1 g m(-2) intravenously (i.v.)
      and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was
      response to TIP. In all, 51 patients were registered, of whom 43 were eligible
      for response assessment. Eight achieved complete remission (CR) and 18 a partial
      remission with negative markers (PR(-ve)); favourable response rate (FRR = CR +
      PR(-ve)) 60%, 95% CI (44-75%); survival at 1 year was 70% (56-84%) and failure
      free survival 36% (22-50%). In the group of 26 patients meeting the 'good-risk'
      criteria described by the Memorial Hospital, the FRR was 73% (52-88%) compared
      with 41% (18-67%) for the 17 'poor-risk' patients. These results are inferior to
      those previously reported for TIP in a single-centre study when it was given more
      intensively, at higher dose and with growth factor support. Nonetheless, TIP as
      described here can cure a substantial proportion of patients.

PMID- 15999103
TI  - Combined effects of GSTP1 and MRP1 in melanoma drug resistance.
AB  - Glutathione-S-transferase Pi1 (GSTP1) and multidrug resistance protein 1 (MRP1)
      are overexpressed in melanoma, a skin cancer notoriously resistant to all current
      modalities of cancer therapy. To investigate the involvement of these detoxifying
      enzymes in the drug resistance of melanoma, an inducible (Tet-On system)
      antisense (AS) RNA strategy was used to specifically inhibit GSTP1 expression in
      A375 cells, a human melanoma cell line expressing high levels of GSTP1 and MRP1.
      Stable transfectant clones were established and analysed for GSTP1 inhibition by
      AS RNA. The clone A375-ASPi1, presenting a specific 40% inhibition of GSTP1
      expression in the presence of doxycycline, was selected. Lowering the GSTP1 level
      significantly increased (about 3.3-fold) the sensitivity of A375-ASPi1 cells to
      etoposide. Inhibitors of glutathione synthesis (BSO), GSTs (curcumin, ethacrynic
      acid), and also of MRPs (MK571, sulphinpyrazone) improved the sensitising effect
      of GSTP1 AS RNA. All these inhibitors had stronger sensitising effects in control
      cells expressing high GSTP1 level (A375-ASPi1 cells in the absence of
      doxycycline). In conclusion, GSTP1 can act in a combined fashion with MRP1 to
      protect melanoma cells from toxic effects of etoposide.

PMID- 15999105
TI  - Summer reading.

PMID- 15999104
TI  - Fertility, gonadal and sexual function in survivors of testicular cancer.
AB  - Modern treatments cure most testicular cancer patients, so an important goal is
      to minimise toxicity. Fertility and sexual functioning are key issues for
      patients. We have evaluated these outcomes in a cross-sectional study of long
      term survivors of testicular cancer. In total, 680 patients treated between 1982
      and 1992 completed the EORTC Qly-C-30(qc30) questionnaire, the associated
      testicular cancer specific module and a general health and fertility
      questionnaire. Patients have been subdivided according to treatment received:
      orchidectomy either alone (surveillance, S n = 169), with chemotherapy (C, n =
      272), radiotherapy (R, n = 158), or both chemotherapy and radiotherapy (C/RT n =
      81). In the surveillance group, 6% of patients had an elevated LH, 41% an
      elevated FSH and 11% a low (< 10 nmol l(-1)) testosterone. Hormonal function
      deteriorated with additional treatment, but the effect in general was small. Low
      testosterone was more common in the C/RT group (37% P = 0.006), FSH abnormalities
      were more common after chemotherapy (C 49%, C/RT 71% both P < 0.005) and LH
      abnormalities after radiotherapy (11% P < 0.01) and chemotherapy (10%, P <
      0.001). Baseline hormone data were available for 367 patients. After treatment,
      compared to baseline, patients receiving chemotherapy had significantly greater
      elevations of FSH (median rise of 6 (IQR 3-9.25) iu l(-1) compared to 3 (IQR 1-5)
      iu l(-1) for S; P < 0.001) and a fall (compared to a rise in the surveillance
      group) in median testosterone levels (-2 (IQR -8.0 to -1.5) vs 1.0. (IQR -4.0
      4.0) P < 0.001). Patients with low testosterone (but not elevated FSH) had lower
      quality of life scores related to sexual functioning on the testicular cancer
      specific module and lower physical, social and role functioning on the EORTC Qly
      C-30. Patients with a low testosterone also had higher body mass index and blood
      pressure. Treatment was associated with reduction in sexual activity and patients
      receiving chemotherapy had more concerns about fathering children. In total, 207
      (30%) patients reported attempting conception of whom 159 (77%) were successful
      and a further 10 patients were successful after infertility treatment with an
      overall success rate of 82%. There was a lower overall success rate after
      chemotherapy (C 71%; CRT 67% compared to S 85% (P = 0.028)). Elevated FSH levels
      were associated with reduced fertility (normal FSH 91% vs elevated 68% P <
      0.001). In summary, gonadal dysfunction is common in patients with a history of
      testicular cancer even when managed by orchidectomy alone. Treatment with
      chemotherapy in particular can result in additional impairment. Gonadal
      dysfunction reduces quality of life and has an adverse effect on patient health.
      Most patients retain their fertility, but the risk of infertility is likely to be
      increased by chemotherapy. Screening for gonadal dysfunction should be considered
      in the follow-up of testicular cancer survivors.

PMID- 15999106
TI  - Getting a grip on O-acetyl-ADP-ribose.

PMID- 15999107
TI  - Doughnuts dealing with RNA.

PMID- 15999108
TI  - P-bodies take a RISC.

PMID- 15999109
TI  - Beginning at the end with SUMO.

PMID- 15999110
TI  - Structural clues to prion mysteries.

PMID- 15999111
TI  - MicroRNAs directing siRNA biogenesis.

PMID- 15999112
TI  - Spliceosome assembly in yeast: one ChIP at a time?

PMID- 15999114
TI  - Rule Britannia.

PMID- 15999115
TI  - Gene expression: growing up together may help genes go their separate ways.

PMID- 15999116
TI  - Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann Syndrome (BWS) results from mutations or epigenetic events
      involving imprinted genes at 11p15.5. Most BWS cases are sporadic and uniparental
      disomy (UPD) or putative imprinting errors predominate in this group. Sporadic
      cases with putative imprinting defects may be subdivided into (a) those with loss
      of imprinting (LOI) of IGF2 and H19 hypermethylation and silencing due to a
      defect in a distal 11p15.5 imprinting control element (IC1) and (b) those with
      loss of methylation at KvDMR1, LOI of KCNQ1OT1 (LIT1) and variable LOI of IGF2 in
      whom there is a defect at a more proximal imprinting control element (IC2). We
      investigated genotype/epigenotype-phenotype correlations in 200 cases with a
      confirmed molecular genetic diagnosis of BWS (16 with CDKN1C mutations, 116 with
      imprinting centre 2 defects, 14 with imprinting centre 1 defects and 54 with
      UPD). Hemihypertrophy was strongly associated with UPD (P<0.0001) and exomphalos
      was associated with an IC2 defect or CDKN1C mutation but not UPD or IC1 defect
      (P<0.0001). When comparing birth weight centile, IC1 defect cases were
      significantly heavier than the patients with CDKN1C mutations or IC2 defect
      (P=0.018). The risk of neoplasia was significantly higher in UPD and IC1 defect
      cases than in IC2 defect and CDKN1C mutation cases. Kaplan-Meier analysis
      revealed a risk of neoplasia for all patients of 9% at age 5 years, but 24% in
      the UPD subgroup. The risk of Wilms' tumour in the IC2 defect subgroup appears to
      be minimal and intensive screening for Wilms' tumour appears not to be indicated.
      In UPD patients, UPD extending to WT1 was associated with renal neoplasia
      (P=0.054). These findings demonstrate that BWS represents a spectrum of
      disorders. Identification of the molecular subtype allows more accurate
      prognostic predictions and enhances the management and surveillance of BWS
      children such that screening for Wilms' tumour and hepatoblastoma can be focused
      on those at highest risk.

PMID- 15999117
TI  - Partners of mutation-carriers for Huntington's disease: forgotten persons?
AB  - This study focuses on psychological distress and coping strategies in partners of
      tested persons 5 years after predictive testing for Huntington's disease. A total
      of 16 carrier-couples and 17 noncarrier-couples participated in the study. Self
      report questionnaires were used, assessing depression level, anxiety, intrusive
      and avoidance thoughts and coping strategies. Partners of carriers have as much
      distress as carriers, and for some distress variables even more (P<0.05-0.001).
      They clearly experience more psychological distress than noncarriers' partners,
      as expected (P<0.05-0.001). Regarding coping strategies, carriers' partners adopt
      more passive strategies (passive-regressive and avoiding reactions; P<0.05) and
      less active strategies (social support seeking and problem solving; P<0.05
      0.001), compared to carriers. For both carriers and partners, the adoption of
      more passive strategies for coping was associated with more distress and the use
      of more active strategies with less distress (for carriers: P<0.05-0.001; for
      carriers' partners: P<0.05). The presence of children before predictive testing
      was an additional result-specific distress factor in carriers and their partners.
      In conclusion, carriers' partners have at least as much psychological distress as
      carriers, but partners have the tendency to draw back. The results suggest that
      the grief of carriers' partners may be 'disenfranchised', or not socially
      recognised, as if they have no right to mourn. We moreover interpreted the
      results referring to concepts such as anticipatory grief, psychological defences,
      dissonance processes and imbalanced partner relationship. Finally, we formulated
      some implications for genetic counselling.

PMID- 15999118
TI  - Effect of short-term finasteride therapy on peroperative bleeding in patients who
      were candidates for transurethral resection of the prostate (TUR-P): a randomized
      controlled study.
AB  - In the present study we aimed to demonstrate the efficacy of short-term
      pretreatment with finasteride in patients undergoing transurethral resection of
      the prostate (TUR-P). For this purpose 40 patients with BPH, who were candidates
      for TUR-P, were randomized into two groups. The first group (n=20) received 5 mg
      finasteride/day for 4 weeks prior to surgery and the second group (n=20) remained
      as the control. Patients who underwent prior prostate or urethral surgery and had
      a diagnosis of prostate cancer or chronic renal failure, patients who received
      finasteride, aspirin, coumadin or similar anticoagulant drugs prior to surgery
      and patients who had capsule perforations or open sinuses during the surgery were
      excluded from the study. All patients had a normal digital rectal examination and
      PSA values less than 4 ng/ml. As we look at the results there was no
      statistically significant difference between the finasteride group and control
      group regarding age, IPSS, PSA, prostate volumes, preoperative serum hemoglobin,
      hematocrit values and mean operating times and used irrigating fluids. The total
      amount of bleeding and bleeding per gram resected tissue were significantly lower
      in the finasteride group regardless of prostate volume. Furthermore the decrease
      in the hemoglobin and hematocrit values was higher in the control group. As a
      conclusion four weeks of finasteride pretreatment provided a significant decrease
      in peroperative bleeding regardless of prostate volume without any major side
      effects.

PMID- 15999119
TI  - Expression of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine
      phosphorylase, and orotate phosphoribosyl transferase in prostate cancer.
AB  - The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD),
      thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) are
      involved in the metabolism of the anticancer drug 5-fluorouracil. No reports have
      examined the expression of these enzymes in prostate cancer (CaP). A total of 25
      previously untreated, hormone-sensitive CaP tissue samples and 11 benign
      prostatic hyperplasia (BPH) specimens were examined. Tissue of CaP and BPH tissue
      samples were obtained from formalin-fixed, paraffin-embedded sections by laser
      captured microdissection, and then RNA was extracted. mRNA expression of TS, DPD,
      TP, and OPRT was analyzed by quantitative reverse transcriptase-polymerase chain
      reaction. TS and OPRT expression levels were significantly higher in CaP samples
      than in BPH. DPD expression level in poorly differentiated CaP was significantly
      lower than that in CaP with more favorable--well or moderately differentiated-
      histopathology.

PMID- 15999120
TI  - Adjuvant and salvage treatment after radical prostatectomy: current practice in
      the UK.
AB  - OBJECTIVE: To survey UK urologists and radiation oncologists in the evaluation
      and treatment of localised prostate cancer in the adjuvant and salvage setting.
      METHODS: Postal questionnaires were mailed to 292 urologists and 98 radiation
      oncologists in the UK. RESULTS: In all, 188 (48%) questionnaires were returned.
      In total, 72/128 (56%) of the urologist respondents and 58/60 (97%) of the
      oncologist respondents perform routine radical prostate treatment. Among 43 (60%)
      of the urologist, 40 (69%) recommended adjuvant treatment, which could be
      radiotherapy, hormonal treatment or combined hormonal and radiation treatment.
      There is no significant difference between the modality of treatment recommended.
      The poor prognostic factors that would influence the decision to offer adjuvant
      treatment include a detectable postoperative PSA, seminal vesicle involvement,
      positive margins, Gleason score>8 and pathological T3. With regard to the choice
      of hormonal treatment, most urologists preferred antiandrogens, whereas most
      oncologists prefer lutienising hormone releasing hormone (LHRH) analogue
      (P=0.03). Regarding salvage treatment, there is a wide variation in the PSA
      threshold and number of PSA rises before initiation of investigations and
      treatment. Significantly more urologists recommended salvage radiotherapy
      (P=0.02), whereas oncologists recommended combined hormonal radiation therapy
      (P=0.03). There is a wide variation of practice regarding the duration of
      hormonal treatment, the type of investigations initiated, range of radiotherapy
      doses and treatment volumes. CONCLUSION: There is a wide variation in practice
      among UK clinicians.

PMID- 15999122
TI  - Penetrating eye injuries in South African children: aetiology and visual outcome.
AB  - PURPOSE: To assess the aetiology, prognosis, and visual outcome of penetrating
      eye injuries in South African children. METHODS: In all, 100 consecutive
      patients, aged 16 years and under, with penetrating ocular injuries undergoing
      surgery between January 2001 and November 2002 were prospectively evaluated.
      RESULTS: Most children (66%) were injured during play. In all, 55% of penetrating
      eye injuries occurred at home, and all injuries to children under the age of 6
      years occurred there. Most injuries occurred in the absence of a caregiver (85%).
      Sticks, wire, and glass caused half of all injuries (48%). The most common
      mechanism of injury was impact with a sharp object (46%). Only 25% of injured
      presented to the hospital within 24 h of injury; the more severe the sustained
      injury and the younger the patient, the earlier was attendance at the clinic.
      Most patients (71%) regained best-corrected visual acuity (Snellen equivalent) of
      20/200 or better, and 51% regained 20/40 or better. Patient age and delay of
      presentation were not of prognostic value. Indicators of poor visual outcome were
      identified as wound size greater than 11 mm in length, mixed corneoscleral type
      wounding, and involvement of the lens and posterior segment in the injury.
      CONCLUSIONS: Penetrating eye injuries in African children, reviewed here,
      generally occur when children are at play in a domestic setting. Effective
      prevention should stress parental awareness, careful supervision, greater home
      safety, safe toys, and avoidance of hazardous games.

PMID- 15999121
TI  - Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that
      zoledronic acid inhibits prostate cancer in bone by indirect mechanisms.
AB  - Zoledronic acid (ZA) has been shown to inhibit prostate tumor growth in vitro and
      have beneficial effects in patients with advanced prostate cancer (CaP). The aim
      of this study was to determine whether ZA exhibits direct anti-tumor effects on
      CaP cells in vivo. To distinguish the effects of inhibition of osteolysis and
      direct anti-tumor activity of ZA in vivo, we compared the results of treatment
      with ZA and osteoprotegerin (Fc-OPG), which inhibits osteolysis, but without
      significant direct anti-tumor effects. In vitro Fc-OPG had no significant effects
      on C4-2 proliferation, whereas ZA decreased proliferation. However, both agents
      decreased tumor growth in bone. Moreover, both increased bone volume and
      prevented the overall decreases in BMD associated with growth of C4-2 cells in
      bone. Our study provides novel and significant observations that the in vivo
      effects of ZA are consistent with indirect effects mediated by osteoclasts.

PMID- 15999123
TI  - Automated detection of wedge-shaped defects in polarimetric images of the retinal
      nerve fibre layer.
AB  - PURPOSE: Automated glaucoma detection in images obtained by scanning laser
      polarimetry is currently insensitive to local abnormalities, impairing its
      performance. The purpose of this investigation was to test and validate a
      recently proposed algorithm for detecting wedge-shaped defects. METHODS: In all,
      31 eyes of healthy subjects and 37 eyes of glaucoma patients were imaged with a
      GDx. Each image was classified by two experts in one of four classes, depending
      on how clear any wedge could be identified. The detection algorithm itself aimed
      at detecting and combining the edges of the wedge. The performance of both the
      experts and the algorithm were evaluated. RESULTS: The interobserver correlation,
      expressed as ICC(3,1), was 0.77. For the clearest cases, the algorithm yielded a
      sensitivity of 80% at a specificity of 93%, with an area under the ROC of 0.95.
      Including less obvious cases by the experts resulted in a sensitivity of 55% at a
      specificity of 95%, with an area under the ROC of 0.89. CONCLUSIONS: It is
      possible to automatically detect many wedge-shaped defects at a fairly low rate
      of false-positives. Any detected wedge defect is presented in a user-friendly
      way, which may assist the clinician in making a diagnosis.

PMID- 15999124
TI  - Reversal of chronic ocular ischaemia with good visual recovery in giant cell
      arteritis.

PMID- 15999125
TI  - Cyclotorsional eye movements during a simulated PRK procedure.
AB  - PURPOSE: Eye alignment is a serious concern when performing corneal surface
      ablation. Although several excimer lasers monitor horizontal and vertical
      movements, little is known about the potential impact of cyclotorsional
      movements. Dynamic cyclotorsions have been measured on 10 emmetropic subjects
      during a simulated PRK treatment. METHODS: Cyclotorsional eye movements were
      measured using a 3D videoculographic system (SMI) in 10 emmetropic subjects in
      upright and supine position. The subjects were wearing an eyelid speculum and
      were asked to fixate on a 1 degrees red spot. The fixation target was either in
      focus or optically degraded by electronic filters. Data were collected at the
      University Eye Clinic, Torino, Italy, and the different setting measurements were
      compared using Student's t-test for paired data. RESULTS: Cyclotorsions were
      significantly higher when subjects were fixating an optically degraded stimulus
      (upright: P=0.04; supine: P=0.0002). The cyclotorsional movements ranged from -13
      to 17 degrees. A significant difference in eye orientation was present when
      changing from the upright to the supine position (P=0.03). Even when correcting
      for this positional error, significantly higher cyclotorsional movements were
      detected in the supine position (in focus: P=0.0043; optically degraded:
      P=0.0008). The torsional range was from -14.85 to 14.55 degrees. CONCLUSIONS: The
      high range of cyclotorsional eye movements during a simulated PRK procedure
      suggests that 3D tracking could improve surface ablation results when treating
      high astigmatism or when wavefront guided.

PMID- 15999126
TI  - Estimating the clinical usefulness of optic disc biometry for detecting
      glaucomatous change over time.
AB  - PURPOSE: First, to determine the absolute measurement precision of scanning laser
      ophthalmoscopy (SLO) parameters, by expressing them as 95% limits of agreement
      (LA(95%)). Second, to propose a method for mathematically estimating the clinical
      ability of a parameter to monitor disease progression, expressed as the
      Discriminating Capacity Index (DCI). METHODS: We measured the optic disc of 14
      healthy volunteers and 14 glaucoma patients. LA(95%)-values were calculated from
      the average standard deviation of three measurements on the same day for
      repeatability, and three measurements on separate days within a 6-week period for
      reproducibility. We then calculated the DCI by dividing the measurement range by
      its LA(95%) in healthy subjects and glaucoma patients separately. Thus, the DCI
      takes into account both the dynamic range of disease progression and the extent
      of measurement variance, providing an index of the possible clinical usefulness
      of a parameter. As the DCI is dimensionless it allows comparison across various
      parameters and across technologies. RESULTS: In the glaucoma group, the SLO
      parameters with the highest DCIs were 'volume below' (DCI, 9.38) and 'mean
      contour depth' (DCI, 8.02). In the healthy group, 'Neuroretinal rim area' had the
      highest index (DCI, 2.15). CONCLUSION: SLO optic disc biometry is uniformly
      reproducible and may prove a clinically useful method for glaucoma follow-up, due
      to the high DCI found for several parameters. The capacity to detect conversion
      from health to glaucoma is less pronounced, possibly due to a larger biological
      variability found in healthy volunteers.

PMID- 15999127
TI  - Patient safety in cataract surgery.
AB  - PURPOSE: The recent focus on healthcare errors and safety suggest that
      practitioners and policy makers might appraise their cataract surgical care from
      a patient safety perspective. This paper reviews patient safety issues relevant
      to cataract care. Causation and consequences of incidents in cataract surgery,
      with implications for policy, are discussed. METHODS: Models of accident
      causation from other domains were drawn on and empirically applied to cataract
      care. Consultation was undertaken with experts in cataract surgery, patient
      safety, and in risk management. Feedback on patient safety was included from
      presentations made to staff and patients and from personal insights. RESULTS:
      Ophthalmology teams should embrace steps to improve patient safety. The role of
      incident reporting is advanced, including the provision of a prompt menu of
      cataract patient safety incidents as suggested by the Royal College of
      Ophthalmologists. CONCLUSIONS: Strict attention to detail, risk assessment, and
      careful consideration of the patient pathway is needed to enhance cataract care.
      Clinical errors, near misses and complications happen, and may provide an
      opportunity for learning to reduce the risk of similar events in the future.
      Investment in staffing and training, appropriate equipment, and development of a
      safety culture with patient involvement are key elements of safe cataract
      surgical care. Patients and the public expect that safe cataract care should be
      commissioned for them. Critical patient safety incidents, including incidents
      that have led to permanent harm, require careful analysis of underlying systems
      and/or root causes.

PMID- 15999128
TI  - 'A Thrip to eye casualty' an unusual complication of Sub-Tenon's anaesthesia.

PMID- 15999129
TI  - Central retinal artery occlusion: association with patent foramen ovale.

PMID- 15999130
TI  - Reply to endophthalmitis following 25-gauge vitrectomy.

PMID- 15999131
TI  - With regards to 'Endophthalmitis' (Editorial, Eye 2004, 18, 555-556).

PMID- 15999132
TI  - Gaze-evoked amaurosis with cavernous sinus meningioma.

PMID- 15999133
TI  - Occlusive retinal vasculitis in a patient with ankylosing spondylitis.

PMID- 15999134
TI  - Inflammatory reaction following cataract surgery and implantation of acrylic
      intraocular lens in rabbits with endotoxin-induced uveitis.
AB  - PURPOSE: To investigate whether inflammatory responses are more severe in uveitic
      eyes than nonuveitic eyes when acrylic intraocular lens (IOL) is implanted after
      cataract surgery. METHODS: Clear lens removal (phacoemulsification and
      aspiration) was conducted and the hydrophobic acrylic IOL (AR40e, AMO) was
      implanted in adult albino rabbits. Just after the operation, rabbits were divided
      into two groups. One group (nine rabbits) received intravitreal injection of
      lipopolysaccharide (LPS, 200 ng/10 microl) into both eyes to induce endotoxin
      induced uveitis (EIU) and the other group (nine rabbits) received intravitreal
      injection of phosphate-buffered saline (PBS, 10 microl) into both eyes as the
      control. Aqueous humour (AH) and IOLs were harvested 1, 3 , and 7 days after the
      intravitreal injection. The infiltrating cell number in AH was counted and the
      protein concentration of AH was measured. IOLs were evaluated morphologically.
      RESULTS: At 1 day after intravitreal injection, both the infiltrating cell number
      in AH and protein concentration of AH were significantly higher in the LPS
      injected group than in the PBS-injected group. Similarly, more inflammatory cells
      attached to the surfaces of the IOLs in the LPS-injected group. However, 7 days
      later, inflammatory reactions subsided and no clear differences in any of the
      parameters examined were observed between the two groups. CONCLUSIONS: At 7 days
      after the operation, inflammatory reactions in eyes implanted with the
      hydrophobic acrylic IOLs were similar in uveitic eyes and nonuveitic eyes. The
      data suggest that the hydrophobic acrylic IOLs may be suitable for patients with
      uveitis.

PMID- 15999135
TI  - Evaluation of the high specificity Screening Program (C-20-1) of the Frequency
      Doubling Technology (FDT) perimeter in clinical practice.
AB  - AIMS: To compare the efficacy of the high specificity Frequency Doubling
      Technology (FDT) Perimeter Screening Program (C-20-1) to standard threshold
      automated perimetry in the diagnosis of open-angle glaucoma. METHODS: A total of
      100 consecutively presenting patients attending a glaucoma clinic who volunteered
      for the study (approximately 30% of whom were attending for an initial visit)
      were examined with the FDT C-20-1 Screening Program and with the Humphrey Field
      Analyzer (HFA) SITA Fast algorithm and Program 24-2. RESULTS: Of the patients, 17
      were excluded due to unreliable visual field results or non-glaucomatous ocular
      abnormalities. In all, 10 patients were diagnosed as normal, 54 with open-angle
      glaucoma, eight with ocular hypertension, and 11 as glaucoma suspects. Of the 54
      glaucomatous patients, 45 exhibited high-tension glaucoma and nine normal tension
      glaucoma. Perimetry with the HFA gave a sensitivity of 81.5% for the combined
      category of glaucoma and glaucoma suspect and a specificity of 83.3% for the
      combined category of normal and ocular hypertension. Perimetry with the FDT gave
      a sensitivity of 74.5% and a specificity of 85.2% compared to that of the HFA.
      CONCLUSION: In the detection of glaucoma, Program C-20-1 of the FDT perimeter
      exhibits high specificity. It exhibits low sensitivity for the detection of mild
      loss but high sensitivity for advanced field loss relative to Program 24-2 and
      the SITA Fast algorithm of the HFA.

PMID- 15999136
TI  - Combined enucleation and orbitotomy for choroidal melanoma with orbital
      extension.

PMID- 15999137
TI  - The effect of an inversion system and the time interval between matings on
      postcopulatory sexual selection in the seaweed fly, Coelopa frigida.
AB  - The seaweed fly, Coelopa frigida, exhibits LMSP. A large chromosomal inversion
      system affects many traits including egg-to-adult viability via heterosis.
      Consequently, there is also considerable potential for cryptic female mate choice
      to operate on the basis of sperm karyotype. Here, we investigated the effect of
      time interval and chromosomal inversion karyotype on postcopulatory sexual
      selection. Homokaryotypic females were mated with a male of the same and a male
      of the opposite homokaryotype. The order of the matings was varied so cryptic
      female mate choice could operate either in concert or antagonistically with LMSP.
      LMSP was found when there was a 24 h time interval between matings, irrespective
      of the order in which the males were mated. However, when the males were mated in
      quick succession the order of mating was important. When LMSP and cryptic female
      mate choice work in concert a high level of LMSP was found. However, when the
      male of opposite homokaryotype mated first, then first male sperm precedence was
      observed. This suggests that polyandrous females might be able to bias paternity
      but only when matings occur in quick succession. Consequently, population density
      is likely to affect the operation of postcopulatory sexual selection.

PMID- 15999138
TI  - Reinforcement of reproductive isolation between adjacent populations in the Park
      Grass Experiment.
AB  - It has been debated, ever since Charles Darwin and Alfred Russell Wallace
      disagreed about the matter, whether natural selection plays a role in reinforcing
      reproductive isolation during the earliest stages of speciation. Recent theory
      suggests that it can do so, but until now the empirical evidence has
      conspicuously lacked a case in which reinforcement has actually been observed to
      split a population. We show that this has occurred at least once in populations
      of the grass Anthoxanthum odoratum growing in the Park Grass Experiment where
      flowering time has shifted at the boundaries between plots. As a consequence,
      gene flow via pollen has been severely limited and adjacent populations that had
      a common origin at the start of the experiment in 1856 have now diverged at
      neutral marker loci.

PMID- 15999139
TI  - Small but not forgotten.

PMID- 15999140
TI  - Medical Genetics: revenge of the thrift.

PMID- 15999141
TI  - Are solitary and gregarious Mormon crickets (Anabrus simplex, Orthoptera,
      Tettigoniidae) genetically distinct?
AB  - Phase polyphenisms are usually thought to reflect plastic responses of species,
      independent of genetic differences; however, phase differences could correlate
      with genetic differentiation for various reasons. Mormon crickets appear to occur
      in two phases that differ in morphology and behaviour. Solitary individuals are
      cryptic and sedentary whereas gregarious individuals form bands, migrate, and are
      aposematically coloured. These traits have been thought to be phenotypically
      plastic and induced by environmental conditions. However, there has been no
      previous investigation of the extent of genetic differences between solitary and
      gregarious populations of this widespread North American species. We sequenced
      two mitochondrial genes, COII and COIII, in samples of Mormon crickets from
      gregarious populations west of the continental divide and solitary mountain
      populations primarily east of the divide. Sequencing revealed two genetically
      distinct clades that broadly correspond with the solitary eastern populations and
      the mainly gregarious western populations. We used coalescent modelling to test
      the hypothesis that the species consists of two deep genetic clades, as opposed
      to a series of equally distinct populations. Results allowed us to reject the
      null hypothesis that a radiation independent of phase produced these clades, and
      molecular clock estimates indicate the time of divergence to be approximately 2
      million years ago. This work establishes that the solitary populations found in
      the mountains on the eastern slope are part of a clade that is genetically
      distinct from the western populations, which are primarily gregarious, and the
      implications of this apparent correlation between phase and genetic
      differentiation are discussed.

PMID- 15999142
TI  - Factors influencing the population structure of Aedes aegypti from the main
      cities in Cambodia.
AB  - A population genetic analysis was conducted on 47 Aedes aegypti collections from
      Cambodia. Genetic differentiation at seven polymorphic isoenzyme loci was
      analysed by starch gel electrophoresis. Low (F(ST)=0.024) but significant (P<10(
      6)) differentiation was found when all samples were considered. Whatever the
      grouping of samples tested, differentiation remained significant but low. The
      role of human activities (ie insecticide treatments or water storage practices)
      and environmental factors (ie rainfall) in shaping mosquito differentiation are
      discussed.

PMID- 15999143
TI  - Evolutionary genetics: a ring of species.

PMID- 15999144
TI  - Stocking impact and temporal stability of genetic composition in a brackish
      northern pike population (Esox lucius L.), assessed using microsatellite DNA
      analysis of historical and contemporary samples.
AB  - During the last decade, brackish northern pike populations in Denmark have been
      subject to stocking programmes, using nonindigenous pike from freshwater lakes,
      in order to compensate for drastic population declines. The present study was
      designed to investigate the genetic impact of stocking freshwater pike into a
      brackish pike population in Stege Nor, Denmark. We analysed polymorphism at eight
      microsatellite loci in samples representing the indigenous Stege Nor population
      prior to stocking (ie from 1956 to 1957), along with a sample of the contemporary
      Stege Nor population and samples from the three populations used for stocking.
      Despite large numbers of stocked fry, the results from both individual and
      population level admixture analyses demonstrated extremely poor performance and
      <1% introgression of stocked freshwater pike into the brackish pike population.
      Furthermore, pairwise F(ST) estimates between samples demonstrated close genetic
      relationship among temporal samples from Stege Nor, indicating temporal stability
      over the last 45 years. We also estimated the effective population size (N(e)) of
      pike in Stege Nor and applied a test for recent population bottlenecks. The
      harmonic mean of N(e) was relatively high (>250), but there were indications of
      bottlenecks in all samples and populations. We ascribe this finding to historical
      rather than recent bottlenecks, possibly dating back to founder events associated
      with postglacial recolonisation.

PMID- 15999145
TI  - Evidence for the preferential involvement of 5-HT2A serotonin receptors in stress
      and drug-induced dopamine release in the rat medial prefrontal cortex.
AB  - The mechanism(s) by which serotonin modulates dopamine release in the medial
      prefrontal cortex is not known, although studies suggest an involvement of 5-HT2
      family receptors. We employed in vivo microdialysis and putatively selective 5
      HT2A antagonists (M100907, MDL 11,939, SR46349B) to determine if 5-HT2A receptors
      are responsible for both drug- and stress-induced DA release in the medial
      prefrontal cortex. MDL 11,939 and SR46349B receptor-binding studies indicated,
      for the first time, that only MDL 11,939 had greater selectivity for the 5-HT2A
      vs the 5-HT2C receptor subtypes similar to M100907, and that both showed low or
      no affinity for non-5-HT2 receptors. Reverse dialysis with 5-HT2A antagonists had
      little or no effect on basal dopamine efflux. However, intracortical
      administration of MDL 11,939 or M100907 attenuated dopamine release induced by
      systemic administration of the 5-HT2 agonist DOI. Dual-probe microdialysis
      demonstrated that systemic DOI also increased glutamate concentrations in the
      ventral tegmental area (VTA). This was blocked by intracortical M100907. Cortical
      perfusion with M100907, or the atypical antipsychotic drug risperidone, but not
      the 5-HT2B/C ligand SB 206553, also decreased dopamine release induced
      physiologically by stress. These results indicate that stimulation of cortical 5
      HT2A receptors increases the release of dopamine from the mesocortical system.
      They suggest that this effect may be mediated by increases in glutamate release
      from corticotegmental projections to the VTA. Additionally, they indicate that
      cortical 5-HT2A receptors modulate evoked dopamine release, such as that observed
      physiologically following mild stress. These findings may have implications for
      the pharmacological treatment of disorders resulting from or exacerbated by
      stress.

PMID- 15999146
TI  - Methylphenidate increases cortical excitability via activation of alpha-2
      noradrenergic receptors.
AB  - Although methylphenidate (MPH), a catecholaminergic reuptake blocker, is
      prescribed for attention-deficit/hyperactivity disorder, there is a dearth of
      information regarding the cellular basis of its actions. To address this issue,
      we used whole-cell patch-clamp recordings to investigate the roles of various
      catecholamine receptors in MPH-induced changes in cortical neuron excitability.
      We bath-applied dopamine or noradrenaline receptor antagonists in combination
      with MPH to pyramidal cells located in deep layers of the infralimbic and
      prelimbic prefrontal cortices. Application of MPH (10 microM) by itself increased
      cortical cell excitability in slices obtained from juvenile rats. This MPH
      mediated increase in excitability was lost when catecholamines were depleted with
      reserpine prior to recording, demonstrating the requirement for a presynaptic
      monoamine component. Antagonist studies further revealed that stimulation of
      alpha-2 noradrenergic receptors mediates the MPH-induced increase in intrinsic
      excitability. Dopamine D1 receptors played no observable role in the actions of
      MPH. We therefore propose that MPH is acting to increase catecholaminergic tone
      in the PFC, and thereby increases cortical excitability by mediating the
      disinhibition of pyramidal cells through mechanisms that may include activation
      of alpha-2 adrenoreceptors located in interneurons.

PMID- 15999147
TI  - Punishment induces risky decision-making in methadone-maintained opiate users but
      not in heroin users or healthy volunteers.
AB  - Reinforcing properties of psychoactive substances are considered to be critically
      involved in the development and maintenance of substance dependence. While
      accumulating evidence suggests that the sensitivity to reinforcement values may
      generally be altered in chronic substance users, relatively little is known about
      the influence reinforcing feedback exerts on ongoing decision-making in these
      individuals. Decision-making was investigated using the Cambridge Risk Task, in
      which there is a conflict between an unlikely large reward option and a likely
      small reward option. Responses on a given trial were analyzed with respect to the
      outcome on the previous trial, providing a measure of the impact of prior
      feedback in modulating behavior. Five different groups were compared: (i) chronic
      amphetamine users, (ii) chronic opiate users in methadone maintenance treatment
      (MMT), (iii) chronic users of illicit heroin, (iv) ex-drug users who had been
      long-term amphetamine / opiate users but were abstinent from all drugs of abuse
      for at least 1 year and (v) matched controls without a history of illicit
      substance use. Contrary to our predictions, choice preference was modified in
      response to feedback only in opiate users enrolled in MMT. Following a loss, the
      MMT opiate group chose the likely small reward option significantly less
      frequently than controls and heroin users. Our results suggest that different
      opiates are associated with distinctive behavioral responses to feedback. These
      findings are discussed with respect to the different mechanisms of action of
      heroin and methadone. Neuropsychopharmacology (2005) 30, 2115-2124.
      doi:10.1038/sj.npp.1300812; published online 6 July 2005.

PMID- 15999148
TI  - Pharmacokinetic profile of single and repeated oral doses of MDMA in squirrel
      monkeys: relationship to lasting effects on brain serotonin neurons.
AB  - A large body of data indicates that (+/-)3,4-methylenedioxymethamphetamine (MDMA,
      'ecstasy') can damage brain serotonin neurons in animals. However, the relevance
      of these preclinical data to humans is uncertain, because doses and routes of
      administration used in animals have generally differed from those used by humans.
      Here, we examined the pharmacokinetic profile of MDMA in squirrel monkeys after
      different routes of administration, and explored the relationship between acute
      plasma MDMA concentrations after repeated oral dosing and subsequent brain
      serotonin deficits. Oral MDMA administration engendered a plasma profile of MDMA
      in squirrel monkeys resembling that seen in humans, although the half-life of
      MDMA in monkeys is shorter (3 vs 6-9 h). MDMA was biotransformed into MDA, and
      the plasma ratio of MDA to MDMA was 3-5 / 100, similar to that in humans. MDMA
      accumulation in squirrel monkeys was nonlinear, and plasma levels were highly
      correlated with regional brain serotonin deficits observed 2 weeks later. The
      present results indicate that plasma concentrations of MDMA shown here to produce
      lasting serotonergic deficits in squirrel monkeys overlap those reported by other
      laboratories in some recreational 'ecstasy' consumers, and are two to three times
      higher than those found in humans administered a single 100-150 mg dose of MDMA
      in a controlled setting. Additional studies are needed on the relative
      sensitivity of brain serotonin neurons to MDMA toxicity in humans and non-human
      primates, the pharmacokinetic parameter(s) of MDMA most closely linked to the
      neurotoxic process, and metabolites other than MDA that may play a role.

PMID- 15999149
TI  - Genomics of pancreatic cancer: does it make any improvement in diagnosis,
      prognosis and therapy?
AB  - Pancreatic cancer (PanC) is an extremely lifethreatening neoplasm due to its late
      discovery, rapid progression and resistance to chemo- and radiotherapy. In the
      past years a significant research attention turned to this cancer. Extensive
      genomic analysis of PanC revealed numerous alterations, however, none of them
      emerged yet as a key regulator of tumor progression. Our increasing knowledge on
      the molecular targets in various cancer types started to change their management.
      Examples of success of the molecular therapies (in CML, GIST, NSCLC) may initiate
      more activity in pancreatic cancer as well.

PMID- 15999150
TI  - Influence of sialic acid removal on MUC1 antigenic reactivity in head and neck
      carcinoma.
AB  - To investigate the influence of sialic acid removal on MUC1 peptidic and
      carbohydrate epitope reactivity in head and neck squamous cell carcinoma (HNSCC),
      tumor samples belonging to 24 HNSCC patients were studied by standard
      immunohistochemistry (IHC) with and without desialylation with 0.1 U/ml
      neuraminidase. From each tumor sample, subcellular fractions were obtained and
      analyzed by SDS-PAGE and Western blotting (WB). Three monoclonal antibodies
      (MAbs) were used: C595 MAb directed to MUC1 protein core, an anti-Tn hapten MAb,
      and an anti-sTn hapten MAb; a comparative analysis between desialylated and
      sialylated samples was performed. By IHC without neuraminidase treatment, 19 of
      24 samples reacted with anti-MUC1 peptidic epitope, while Tn hapten was not
      detected and sTn was found in 1 of 24 cases. Desialylation increased either the
      number of reacting cells or the intensity of the reaction with C595 and anti-Tn
      MAbs, and some negative samples became positive. On the other hand, sTn
      expression decreased with desialylation. By WB, several bands from >200 to 25 kDa
      were found; desialylation increased high-molecular-weight bands, diminishing the
      detection of low-molecular-weight ones. The use of desialylation is a suitable
      treatment that contributes to the exposure of MUC1-associated epitopes, which may
      be related to the spreading of HNSCC.

PMID- 15999152
TI  - The effect of tumor invasion patterns on pathologic stage of bladder urothelial
      carcinomas.
AB  - The aim of this study was to investigate tumor invasion pattern, its
      heterogeneity and association with histopathological features and stage in
      invasive urothelial carcinoma of the bladder. We studied 62 cases of invasive
      urothelial carcinoma of the bladder. World Health Organization (WHO) 1973,
      WHO/ISUP 1998 and WHO 1999 systems were used for tumor grading. Pathologic
      staging of each case was done according to 1997 TNM system. During evaluation of
      the slides three main tumor invasion patterns were detected: "nodular",
      "trabecular" and "infiltrative". In addition, homogeneity or heterogeneity of
      invasion patterns was also recorded for each case. Of sixty-two invasive cases,
      17 (27%) had nodular, 36 (58%) trabecular, and 9 (15%) infiltrative invasion
      pattern. There was a statistically significant difference between invasion
      patterns in relation to pathologic stage (pT) (p=0.001), but not to grade. Of the
      17 cases with nodular invasion pattern and 36 tumors with trabecular invasion
      pattern, 13 (77%) and 26 (72%) were pT1, respectively, whereas 8 of 9
      infiltrative cases (89%) were advanced stage (pT2-3). According to heterogeneity,
      forty-two cases (68%) had homogeneous, while the remaining 20 (32%) had
      heterogeneous invasion pattern. Of the 42 homogeneous cases 34 (81%) were pT1,
      whereas 14 of 20 heterogeneous cases (70%) were advanced stage (p=0.000). The
      different invasion patterns seem to have a large impact on pathologic stage,
      especially the infiltrative pattern. In addition, invasion heterogeneity appears
      to be of value in determination of biologic aggressiveness in urothelial
      carcinoma.

PMID- 15999151
TI  - Maternally inherited deafness and unusual phenotypic manifestations associated
      with A3243G mitochondrial DNA mutation.
AB  - The mitochondrial DNA A3243G transition is a fairly common mutation which often
      associates with a MELAS (mitochondrial encephalomyopathy, lactic acidosis and
      stroke-like episodes) phenotype, however, a broad variety in the associated
      clinical picture has also been described. The patient reported here developed a
      generalized seizure at age 12, which was followed by bilateral hearing loss and
      occasional fatigue. The maternal inheritance pattern of hearing loss pointed to a
      possible mitochondrial origin, which was confirmed by molecular analysis of the
      mitochondrial DNA, revealing a heteroplasmic A3243G transition. Interestingly,
      muscle biopsy showed ragged-red fibers in the proband, which is unusual in the
      deafness-associated forms of this mitochondrial disorder. In addition to hearing
      impairment in four generations of the family, fatal cerebral embolization in the
      mother and fatal heart attack in the maternal grandmother (both at age 33) also
      occurred. On the contrary, diabetes, which usually accompanies the hearing loss
      variant, was specifically absent in all generations. The unusual manifestations
      associated with this mutation somewhat differentiate this family from the already
      known variants.

PMID- 15999153
TI  - Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive
      ductal breast carcinoma.
AB  - A major focus of tumor immunology is to reveal the potential role and capacity of
      immunocompetent cells found in different solid tumor tissues. The most abundant
      infiltrating cells (TIL), the T lymphocytes have been investigated in details
      concerning T-cell receptor usage and specificity. However, B cells have hardly
      been investigated in this respect, although high cellular B-cell infiltration has
      been correlated with improved patients' survival in some breast carcinomas. This
      led to our objectives to study variable region gene usage of the tumor
      infiltrating B cells in different breast carcinoma types. By defining the
      immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most
      common invasive ductal carcinoma (IDC) of the breast we compared it to the rare
      medullary breast carcinoma (MBC). After phenotyping infiltrating ductal
      carcinomas, B cells were obtained from tumor tissue by microdissection technique.
      Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified,
      cloned, sequenced, and comparatively analyzed. Some characteristics were found
      for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal
      carcinoma are highly matured and oligoclonal. We conclude that Ig variable region
      gene usage reveals similar and distinguishable characteristics of TIL-B
      immunoglobulin repertoires, which are representative of the nature of the immune
      responses in invasive ductal and medullary breast carcinomas.

PMID- 15999154
TI  - Association of TNF-alpha and TNF-beta gene polymorphism with steroid receptor
      expression in breast cancer patients.
AB  - The presence of estrogen and progesterone receptors is correlated with good
      prognosis in breast cancer. The effect of TNF-alpha on down-regulation of
      estrogen receptor and blocking the proliferative response of breast cancer cells
      to estradiol have been demonstrated. However, the effect of TNFA and TNFB gene
      polymorphisms on the expression of steroid receptors in breast cancer cells is
      not well documented. Therefore, 160 breast cancer patients were recruited to
      investigate the association of TNFA and TNFB gene polymorphism with the level of
      steroid receptor expression. This association was not found to be significant for
      TNFA polymorphism and estrogen receptor expression (p=0.07). However, when
      combined genotypes of TNFA and TNFB polymorphism was considered, homozygous
      patients for lower TNF-alpha producer genotypes (TNFA1/A1 and TNFB1/B1) showed
      significantly higher progesterone receptor expression (p=0.041). Our findings
      indicate that TNFA and TNFB polymorphisms may be associated with the levels of
      steroid receptor expression in breast cancer patients. Further studies on a
      larger group of breast cancer patients are recommended.

PMID- 15999155
TI  - Proliferative lesions of prostate: a multivariate approach to differential
      diagnosis.
AB  - Prostatic needle biopsies from 142 patients were studied: 61 cases were "benign",
      19 atypical small acinar proliferation, 31 high-grade prostatic intraepithelial
      neoplasia, and 31 adenocarcinoma. Using univariate analysis of 46 previously
      described morphological features, 16 variables were selected, which were followed
      by multivariate discriminant analysis. Of these parameters, seven (glandular
      fusion, crystalloids, nucleolomegaly, papillary architecture, visibility of basal
      cell layer, areas of normal luminal cell nucleus/cytoplasm ratio and areas of
      high luminal cell nucleus/cytoplasm ratio) remained significant in discriminating
      the groups. Multivariate analysis selected a small panel of histological features
      as those most helpful in the differential diagnosis of proliferative lesions in
      prostate biopsies.

PMID- 15999156
TI  - Expression of osteopontin and CD44 molecule in papillary renal cell tumors.
AB  - The aim of the study was to analyze the expression of CD44 adhesion molecule and
      its ligand osteopontin in papillary renal cell tumors, and to assess the possible
      prognostic significance of CD44 and osteopontin expression in papillary renal
      cell carcinomas. The expression of the standard and v6 exon containing isoforms
      of CD44 molecule, as well as of its ligand osteopontin, was immunohistochemically
      evaluated in 43 papillary renal cell tumors, which included 5 adenomas and 38
      carcinomas. In order to assess their prognostic significance, the results
      obtained in papillary renal cell carcinomas were compared to usual
      clinicopathological parameters such as tumor size, histological grade,
      pathological stage, and Ki-67 proliferation index. Normal renal tissue was
      negative for CD44s and v6 isoforms, while the expression of osteopontin was found
      in distal tubular epithelial cells in the form of cytoplasmic granular
      positivity. CD44s and v6 isoforms were upregulated in 22 (58%) and 12 (32%) out
      of 38 carcinomas, respectively. Among all clinicopathological parameters
      examined, we only found significant association of CD44s-positive carcinomas with
      lower pathological stage (p=0.026). Papillary renal cell adenomas were generally
      negative for CD44s, except for focal positivity found in one sample. The
      osteopontin protein was detected in all adenomas and all papillary renal cell
      carcinomas, except one. Our results show constitutive expression of osteopontin
      in papillary renal tumors, including papillary renal cell adenomas. The
      upregulation of CD44s and v6 isoforms, although found in a considerable number of
      papillary renal cell carcinomas, does not appear to have any prognostic value in
      this type of renal cancer.

PMID- 15999158
TI  - Histopathological evaluation of renal vascular changes in rats exposed to passive
      smoking.
AB  - Cigarette smoking is an important risk factor for renal damage due to its effects
      on small interlobular arteries. We investigated the effects of long-term passive
      smoking on renal vascular structures in healthy rats exposed to smoke soon after
      birth. Forty-two Sprague-Dawley rats (21 males and 21 females) exposed to passive
      smoking comprised the experimental group and 33 non-exposed rats (17 males and 16
      females) comprised the control group. The number of renal vessels, as well as the
      level of glomerular capillary sclerosis, hyalinosis of arterioles, and myointimal
      hyperplasia of arteries was assessed in renal biopsy specimens. The mean number
      of renal vessels in male and female rats exposed to passive smoke (21.71 and
      13.81, respectively) did not significantly differ from the mean number of renal
      vessels in male and female control rats (22.47 and 13.06, respectively) (p>0.05).
      Levels of glomerulosclerosis, hyalinosis, and myointimal hyperplasia also did not
      differ between the experimental and control groups (p>0.05). Histopathologic
      evidence of renal vascular damage was not found in young rats exposed to passive
      smoke for 4 months. A longer or higher degree of exposure to cigarette smoke
      components may be required before such changes manifest, and aging and primary
      renal disease may play a role.

PMID- 15999160
TI  - Presentations of shortness of breath in Australian general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of the consultations in general practice
      involving a patient presentation of shortness of breath. This provides a backdrop
      against which articles in this issue of Australian Family Physician can be
      further considered.

PMID- 15999157
TI  - Expression of Ki-67 and squamous intraepithelial lesions are related with HPV in
      endocervical adenocarcinoma.
AB  - To estimate the association between human papillomavirus (HPV) status and the
      expression of p53, Ki-67 and bcl-2 in cases of endocervical adenocarcinoma, and
      the relation with squamous intraepithelial lesions (SIL) and age, 229 cases were
      selected, treated between 1995 and 2003 in the Hospital Nossa Senhora da
      Conceicao. All samples were evaluated by polymerase chain reaction to determine
      HPV status. Immunohistochemical technique was used to investigate the expression
      of p53, Ki-67 and bcl-2. The joint occurrence of endocervical adenocarcinoma and
      SIL were estimated too. In the 229 evaluated cases, 182 cases (79.48%) were
      associated with the presence of the HPV. The most common types were HPV18 (93
      cases - 51.09%) and HPV16 (62 cases - 34.06%). Expression of Ki-67 (p=0.009) and
      the presence of SIL (p=0.018) were associated to HPV infection. Expression of p53
      (p=0.647) and bcl-2 (p=0.671) were not related to HPV status. The mean age of the
      patients was 53.2 years, without clear correlation between age group and HPV
      (p=0.095). The presence of HPV, especially type 18 in endocervical adenocarcinoma
      suggests that this agent can be an important cofactor in the development and
      progression of glandular neoplasms of the uterine cervix. The joint occurrence of
      endocervical adenocarcinoma and SIL may support this hypothesis. HPV may promote
      an increased proliferation index in endocervical adenocarcinoma, shown by the
      expression of Ki-67.

PMID- 15999161
TI  - "I can't breathe"--assessment and emergency management of acute dyspnoea.
AB  - BACKGROUND: Acute dyspnoea is a distressing symptom that can suddenly affect any
      age group. OBJECTIVE: The article provides an approach to the identification of
      causes and initial management of acute dyspnoea based on history, physical
      assessment, appropriate triage and investigation. DISCUSSION: Successful
      management includes rapid assessment of the extent of the disease process, with
      emphasis on maintenance or protection of airway integrity and identification of
      impending respiratory failure. All general practice surgeries must have the
      appropriate equipment available, and staff trained in its use, to provide
      immediate relief to any patient who presents with dyspnoea. Urgent transfer from
      the general practice setting to a more specialised centre is usually necessary.

PMID- 15999162
TI  - Management of an acute asthma attack.
AB  - BACKGROUND: Despite a more proactive approach to asthma management, which
      includes an increased range of drugs, wide dissemination of guidelines, and the
      use of asthma action plans, an acute severe asthma attack is one of the most
      common emergencies a general practitioner will encounter. OBJECTIVE: This article
      discusses the management of an acute asthma attack in the general practice
      setting. DISCUSSION: Assessment of severity is vital and can be ascertained quite
      quickly with a brief history and rapid physical examination. It is important to
      remember that wheeze is an unreliable indicator of the severity of attack and may
      be absent in severe asthma. The cornerstones of treatment are oxygen and inhaled
      beta 2 agonists. Beta 2 agonists can be given continuously in severe life
      threatening asthma. Early administration of systemic steroids is important.
      Patients discharged to home after treatment of an asthma attack require close
      follow up including beta 2 agonists for symptom control, review of medications
      including a consideration of a short course of oral steroids, a written asthma
      action plan and detailed advice about what to do in case of deterioration in the
      next 24 hours. They should be reviewed in 24-48 hours.

PMID- 15999163
TI  - Spirometry: an essential clinical measurement.
AB  - BACKGROUND: Respiratory disease is common and amenable to early detection and
      management in the primary care setting. Spirometric evaluation of ventilatory
      function plays a critical role in the diagnosis, differentiation and management
      of respiratory illness such as asthma, chronic obstructive pulmonary disease and
      restrictive lung disorders, and is important in the assessment of lung health in
      smokers and those exposed to occupational and environmental hazards. OBJECTIVE:
      This article covers the basic theory, fundamentals of test indications,
      performance and equipment, the interpretation of results and the nuances behind
      the spirogram and the flow-volume curve. DISCUSSION: The use of spirometry by
      primary care physicians, practice nurses and physiotherapists is now practicable
      and supported by a comprehensive range of devices, training courses and reference
      materials. Systematic use of ventilatory assessment both in the clinic and with
      patient self monitoring of peak flow and FEV1 has the capacity to improve patient
      understanding, confidence in self management, and quality of life for those with
      lung disease. Spirometry may also provide a useful modality for following the
      progress of those with neuromuscular disease and incipient respiratory muscle
      weakness and for the promotion of respiratory health in the community setting,
      although further research in all these areas is required.

PMID- 15999164
TI  - Shortness of breath--is it chronic obstructive pulmonary disease?
AB  - BACKGROUND: Of all the major diseases, chronic obstructive pulmonary disease
      (COPD) is the one for which the burden is increasing the fastest. OBJECTIVE: This
      article discusses the diagnoses and assessment of COPD, and provides management
      guidelines including smoking cessation, bronchodilator therapy, the use of
      inhaled corticosteroids, combination therapies, oxygen therapy, and
      rehabilitation. DISCUSSION: Diagnosis is by clinical suspicion in patients with
      an appropriate clinical history and airflow obstruction is confirmed using
      spirometry. Although smoking cessation and oxygen in selected individuals are the
      only interventions known to alter the natural history of COPD, many other
      treatments can significantly lessen breathlessness, reduce exacerbations, and
      improve exercise and quality of life.

PMID- 15999165
TI  - Chronic heart failure--optimising care in general practice.
AB  - BACKGROUND: Chronic heart failure (CHF) is a significant cause of mortality and
      morbidity in developed countries where it predominantly affects elderly persons
      with a range of other comorbid conditions requiring polypharmacy. In Australia,
      over 300 000 people are affected by CHF. Quality general practice forms the
      cornerstone for early diagnosis and evidence based integrated care. OBJECTIVE:
      This article examines the epidemiology of CHF, its clinical diagnosis,
      contemporary management and future treatment possibilities, as well as current
      barriers to optimal care. DISCUSSION: The global prevalence of CHF is rising.
      Optimal treatment requires a coordinated interdisciplinary approach using a
      biopsychosocial model of care in order to maximise compliance with therapy.
      Pharmacological treatment is essential and should include an angiotensin
      converting enzyme inhibitor and beta blocker where possible. Device based
      treatment and cardiac surgery may benefit selected cases.

PMID- 15999166
TI  - Pulmonary embolism--assessment and management.
AB  - BACKGROUND: Pulmonary embolism (PE) is a potentially life threatening disorder
      most commonly seen in debilitated patients with other common medical problems.
      OBJECTIVE: This article aims to increase the reader's understanding of the
      aetiology and pathophysiology of PE so as to identify particular at risk
      patients. An approach to investigation and management will also be explored.
      DISCUSSION: Pulmonary embolism has an incidence of approximately two per 1000 per
      year, generally as a consequence of deep venous thrombosis (DVT), in the setting
      of immobility. Deep venous thrombosis and PE during a prolonged airline flight in
      an otherwise fit person is a rare event. Clinical assessment and simple
      investigations form the basis of initial evaluation. The confirmatory test is
      generally a ventilation/perfusion lung scan or a computerised tomography
      pulmonary angiogram. There is still considerable discussion as to which is the
      better test--both are valid if performed to acceptable standards--thus local
      factors often determine which is performed. Further tests may be needed in those
      with intermediate probability of PE after a confirmatory test. These patients,
      and those presenting with massive PE, may require pulmonary angiography (still
      regarded as the gold standard test). Treatment is anticoagulation, typically with
      low molecular weight heparin followed by 6 months of warfarin. Thrombolytic
      therapy is reserved for the acute massive presentation. Appropriate treatment
      reduces mortality substantially, however, rarely the clot remains unresolved and
      thromboembolic pulmonary hypertension (requiring expert evaluation) develops.

PMID- 15999167
TI  - Managing panic disorder in general practice.
AB  - BACKGROUND: Panic disorder (PD) is common in the community and contributes to
      significant distress and decreased quality of life for people who suffer from it.
      Most people with PD will present in the first instance to their general
      practitioner or hospital emergency department for assistance, often with a focus
      on somatic symptoms and concerns. OBJECTIVE: This article aims to assist the GP
      to manage this group of patients by providing an outline of aetiology, approaches
      to assessment, and common management strategies. DISCUSSION Although GPs have an
      important role to play in ruling out any causal organic basis for panic symptoms,
      the diagnosis of PD can usually be made as a positive diagnosis on the basis of
      careful history taking. Thorough and empathic education is a vital step in
      management. The prognosis for PD can be improved by lifestyle changes, specific
      psychological techniques, and the judicious use of pharmacotherapy.

PMID- 15999168
TI  - An integrative approach to asthma.
AB  - BACKGROUND: Conventional asthma management has provided significant symptomatic
      relief for asthma sufferers, as well as having saved the lives of many asthma
      patients. However, many patients with asthma--and the parents of children with
      asthma--are increasingly seeking to improve asthma control and quality of life,
      and reduce medication dosage by using an integrative medicine (IM) approach to
      their asthma management. This approach incorporates lifestyle interventions,
      psychological approaches, and complementary therapies. OBJECTIVE: This article
      reviews some of the evidence for the IM approach to asthma including
      complementary medicine (CM), lifestyle and mind-body strategies; and discusses
      some of the practical and safety issues involved. DISCUSSION: Many patients
      report significant benefits from broadening their approach to asthma, but there
      is also the potential risk of some patients to make unsafe treatment choices and
      possibly forego adequate supervision. Unfortunately, many patients do not inform
      their general practitioner about their use of CM. Medical education has not
      traditionally trained doctors to be aware of evidence based lifestyle and CM
      treatment options. The informed GP plays a vital role in supervision, educating
      patients about valid and safe treatment options, decision making, and supporting
      legitimate patient empowerment in their own management. An evidence based
      integrative approach offers the best potential outcomes for doctor, patient and
      family.

PMID- 15999169
TI  - Cervical screening and human papillomavirus.
AB  - BACKGROUND: Cervical screening in Australia has been successful in reducing the
      incidence and mortality of cervical cancer. Human papilloma virus (HPV) is a
      common sexually transmitted infection and an integral agent in the development of
      cervical cancer. OBJECTIVE: This article discusses cervical screening, HPV
      infection and counselling women with low grade abnormalities on cervical
      cytology. DISCUSSION: For most women, detectable HPV infection is transient and
      subclinical. While HPV is a precursor to cervical cancer, this is a rare outcome
      of HPV infection. Minor abnormalities on cervical cytology reflecting acute HPV
      infection are common. Women with low grade Pap test abnormalities require
      reassurance and education about the prevalence and natural history of HPV.

PMID- 15999170
TI  - Making sense of breast pathology.
AB  - An understanding of breast pathology is essential when caring for women with
      breast disease. Part five of this series discusses the spectrum of common benign
      and malignant conditions including the distinction between invasive and
      noninvasive breast cancer. It also aims to increase the general practitioner's
      confidence in understanding breast pathology reports, arranging appropriate
      referral for patients, and educating women about their disease.

PMID- 15999172
TI  - Should I report the death to the Coroner?
AB  - The aim of this article is to outline the circumstances in which a general
      practitioner should report a patient's death to the Coroner.

PMID- 15999173
TI  - Complementary and alternative medicine. Part 1--what does it all mean?
AB  - This is the first of a two part series exploring issues around the use of
      complementary and alternative medicine in the Australian general practice
      context. Part 1 discusses the definitions of "complementary and alternative
      medicine" and their use in the community. Part 2 will give an overview of the
      available evidence for the benefits and risks of complementary and alternative
      medicine and an approach to accessing that evidence.

PMID- 15999174
TI  - Psychological distress among GPs--who is at risk and how best to reach them?
AB  - OBJECTIVE: To identify key characteristics of psychologically distressed general
      practitioners and whether these GPs volunteered for a "GP health" educational
      program. SETTING: Eight Australian divisions of general practice responding to an
      invitation to participate in the research in 1999, representing 1356 GPs. MAIN
      OUTCOME MEASURE: The General Health Questionnaire (GHQ-12), together with
      demographic and practice questions. DESIGN: Observational study of GPs invited to
      participate in a voluntary education program on GP health offered through each
      division of general practice. PARTICIPANTS: 819/1356 GPs responded to the
      baseline questionnaire (60%). Of these, 233/819 (28%) scored above the GHQ-12
      threshold indicating psychological distress. Ninety GPs enrolled in the program,
      data were available for 69 GPs. RESULTS: General practitioners who were
      identified as being psychologically distressed were over-represented in the 35-49
      years age group (p=0.02) and were more likely to be the practice principal
      (p=0.04). Over 62% of enrolled GPs had scores that indicated none to mild
      distress. Of those GPs who were distressed, 42% were from the identified at risk
      age group, and 44% were practice principals. DISCUSSION: Alternative targeted
      interventions may be needed to reach GPs with high levels of psychological
      distress.

PMID- 15999175
TI  - How do Victorian GPs manage patients with depression?
AB  - BACKGROUND: Depression is common, yet management in general practice is poorly
      described, especially the relationship between medication use and focussed
      psychological strategies. Government initiatives are targeting general
      practitioners' provision of mental health care. METHODS: Postal survey of a
      random sample of 350 Victorian GPs between November 2001 and April 2002. RESULTS:
      Forty-eight percent response rate. Most GPs reported prescribing medication (82%)
      or providing supportive counselling (87%) to most patients with mild to moderate
      major depression, while few (<20%) reported frequently using focussed
      psychological strategies. Training in psychiatry or focussed psychological
      strategies was associated with use of psychological therapies. DISCUSSION: Future
      education programs that support GPs to overcome barriers to using focussed
      psychological strategies may provide more effective care.

PMID- 15999177
TI  - Chemical science in China.

PMID- 15999176
TI  - Patients with diabetes and impaired glucose tolerance--is it feasible to screen
      for depression?

PMID- 15999178
TI  - From alpha-helix to beta-sheet--a reversible metal ion induced peptide secondary
      structure switch.
AB  - Here we introduce a peptide model based on an alpha-helical coiled coil peptide,
      providing a simple system which can be used for a systematic study of the impact
      of different metal ions in different oxidation states on peptide secondary
      structure on a molecular level; histidine residues were incorporated into the
      heptad repeat to generate possible complexation sites for Cu2+ and Zn2+ ions.

PMID- 15999179
TI  - A new charge derivatization procedure for peptide sequencing.
AB  - Derivatization of peptides by a trityl cation-containing group and collision
      induced dissociation measurements of the cationized peptides results in
      informative spectra that simplify peptide sequencing.

PMID- 15999180
TI  - Enzyme-cleavable linkers for peptide and glycopeptide synthesis.
AB  - Hydroxymethylphenoxy linkers that are commonly used in solid phase peptide
      synthesis are surprisingly susceptible to efficient cleavage by the protease
      chymotrypsin with a broad range of amino acid residues being tolerated at the
      scissile bond; this enzyme-cleavable linker system has been applied to peptide
      and glycopeptide synthesis.

PMID- 15999181
TI  - L-Tartaric acid assisted binary organogel system: strongly enhanced fluorescence
      induced by supramolecular assembly.
AB  - A new series of binary organogels, which showed good gelated capability and
      strongly enhanced fluorescence emission, were designed and prepared by simply
      mixing two components of L-tartaric acid and alkoxyl substituted stilbazoles. It
      was found that L-tartaric acid could not only introduce stilbazole with
      fluorescent property into the gel system, but also provided a main motif for the
      formation of the gel-phase via multiple hydrogen bonds. Meanwhile, pi-pi
      interactions between the complexes also played a key role in the gel formation.
      The decreased nonradiative process, suggested by the longer fluorescent lifetime
      of aggregates than that of monomers and the presence of the J-aggregation for the
      aggregated state, favored the enhanced fluorescence emission.

PMID- 15999182
TI  - Preparation of polymer-supported Ru-TsDPEN catalysts and use for enantioselective
      synthesis of (S)-fluoxetine.
AB  - Polymer-supported chiral ligands 9 and 17 were prepared based on Noyori's (1S,2S)
      or (1R,2R)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine. The combination with
      [RuCl2(p-cymene)]2 has been shown to exhibit high activities and
      enantioselectivities for heterogeneous asymmetric transfer hydrogenation of
      aromatic ketones (19a-c) with formic acid-triethylamine azeotrope as the hydrogen
      donor, whereby affording the respective optically active alcohols 20a-c, the key
      precursors of chiral fluoxetine. As exemplified by ligand 17 for substrate 19c,
      the catalysts can be recovered and reused in three consecutive runs with no
      significant decline in enantioselectivity. The procedure avoids the plausible
      contamination of fluoxetine by the toxic transition metal species.

PMID- 15999183
TI  - Cyclodextrins as carriers for cinchona alkaloids: a pH-responsive selective
      binding system.
AB  - A series of cyclodextrin-cinchona alkaloid inclusion complexes were prepared from
      beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin and heptakis(2,3,6
      tri-O-methyl)-beta-cyclodextrin and four cinchona alkaloids in ca. 90% yields,
      and their inclusion complexation behavior was investigated at pH 7.2 and 1.5 by
      means of fluorescence, UV/Vis and 2D NMR spectroscopy. The results showed that
      the cinchona alkaloids can be efficiently encapsulated in the cyclodextrin cavity
      in an acidic environment and sufficiently released in a neutral environment,
      which makes these cyclodextrin derivatives the potential carriers for cinchona
      alkaloids. The binding ability and molecular selectivity of cyclodextrins toward
      cinchona alkaloids were discussed from the viewpoint of the size-fit concept and
      multiple recognition mechanism between host and guest.

PMID- 15999184
TI  - New approaches towards the synthesis of the side-chain of mycolactones A and B.
AB  - New approaches towards the synthesis of the C1'-C16' side-chain of mycolactones A
      and B from Mycobacterium ulcerans are reported. Chiral building block 4 (Fig. 2)
      with the correct stereochemistry was obtained starting from naturally occurring
      monosaccharides, i.e. D-glucose or L-rhamnose. The polyunsaturated moiety 3 was
      synthesized in only 3 steps from 2,4-dimethylfuran. The building blocks were
      connected through a Sonogashira coupling resulting in the fast and convergent
      assembly of an 8,9-dehydro analogue 2 of the side-chain of mycolactones A and B.
      The synthesis of 1 is at this stage hampered by the lack of a selective partial
      hydrogenation protocol for alkynes embedded in a conjugated system. Alternative
      strategies involving palladium catalyzed sp2-sp2 coupling between C7' and C8' or
      C9' and C10' (Fig. 1) were also explored.

PMID- 15999185
TI  - Synthesis and evaluation of a new non-fluorescent quencher in fluorogenic
      oligonucleotide probes for real-time PCR.
AB  - A non-fluorescent quencher, based on the diaminoanthraquinone Disperse Blue 3,
      has been incorporated into oligonucleotides at the 5'-end, the 3'-end and
      internally as a thymidine derivative. Fluorimetry and fluorogenic real-time PCR
      experiments demonstrate that the quencher is effective with a wide range of
      fluorescent dyes. The anthraquinone moiety increases the melting temperature of
      DNA duplexes, thus allowing shorter, more discriminatory probes to be used. The
      quencher has been used in Scorpion primers and TaqMan probes for human DNA
      sequence recognition and mutation detection.

PMID- 15999186
TI  - Synthesis of 5-, 6- and 7-substituted-2-aminoquinolines as SH3 domain ligands.
AB  - The Src homology 3 (SH3) domains are small protein-protein interaction domains
      that mediate a range of important biological processes and are considered
      valuable targets for the development of therapeutic agents. We have been
      developing 2-aminoquinolines as ligands for SH3 domains--so far the only reported
      examples of entirely small-molecule ligands for the SH3 domains. The highest
      affinity 2-aminoquinolines so far identified are 6-substituted compounds. In this
      article, the synthesis of several new 2-aminoquinolines, including 5-, 6- and 7
      substituted compounds, for Tec SH3 domain ligand binding studies is presented. As
      a part of the synthetic investigation, the utility of different methods for the
      synthesis of 2-aminoquinolines was explored and potentially powerful methods were
      identified for the synthesis of 2-aminoquinolines with diverse functionality. Of
      the compounds prepared, the 5-substituted-2-aminoquinolines generally bound with
      similar affinities to unsubstituted 2-aminoquinoline, whilst the 7-substituted
      compounds generally bound with similar or lower affinity than unsubstituted 2
      aminoquinoline. However, the 6-substituted-2-aminoquinolines generally bound with
      significantly higher affinity than unsubstituted 2-aminoquinoline. In addition,
      one 6-substituted-N-benzylated-2-aminoquinoline was also tested for SH3 binding
      and some evidence for the formation of additional contacts at other regions of
      the SH3 domain was found. These results provide new and useful SAR information
      that should greatly assist with the challenge of developing high affinity small
      molecule ligands for the SH3 domains.

PMID- 15999187
TI  - Vibrational spectra, co-operative intramolecular hydrogen bonding and
      conformations of calix[4]arene and thiacalix[4]arene molecules and their para
      tert-butyl derivatives.
AB  - The IR and Raman spectra and conformations of calix[4]arene, thiacalix[4]arene
      and their p-tert-butyl derivatives have been analysed within the framework of
      scaled quantum mechanics (SQM). It is shown that the introduction of four p-tert
      Bu groups into the calixarene molecules influences the relative energies of their
      conformers and the enthalpy of the cooperative intramolecular H-bonding
      (DeltaH(intra)) almost negligibly. DeltaH(intra), evaluated from Iogansen's rule,
      amounts to approximately 26-28 kcal mol(-1) for the calixarenes and approximately
      20-21 kcal mol(-1) for the thiacalixarenes, which essentially exceeds the
      enthalpies of non-cooperative H-bonds formed by related phenols. As a result of
      this strong bonding, bands of stretching, bending and torsion vibrations of an
      eight-membered cyclic system (OH...)4 arise, e.g., two delta(OH)4 bands are
      observed in the IR spectra of the most highly symmetric C4 cone conformations of
      calix[4]arene and thiacalix[4]arene. The "duplication" of the number of OH
      infrared bands is a good new indicator of cooperativity of intramolecular H
      bonding of the calixarenes.

PMID- 15999188
TI  - Enantioselective Friedel-Crafts type addition of indoles to nitro-olefins using a
      chiral hydrogen-bonding catalyst--synthesis of optically active tetrahydro-beta
      carbolines.
AB  - The enantioselective Friedel-Crafts addition of indoles to nitro-olefins using
      chiral hydrogen-bonding bis-sulfonamides as the catalysts has been developed. The
      reactions, in the presence of only 2 mol% catalyst, generally proceed in high
      yields and with enantioselectivities up to 64% ee, and the enantiomeric excess
      can be improved to >98% ee by recrystallization. Various synthetic
      transformations of the Friedel-Crafts adducts are demonstrated: the nitro group
      can easily be reduced to the corresponding amine and the product obtained can
      undergo a stereocontrolled Pictet-Spengler cyclization to give, for example,
      enantiopure tetrahydro-beta-carbolines. The X-ray structure of the chiral bis
      sulfonamides has been determined and based on these structures the mechanism for
      the stereoselectivity in the reaction is discussed.

PMID- 15999189
TI  - Two structural types of 1,3-alternate tetrapropoxycalix[4]arene derivatives in
      the solid state.
AB  - The solid state structures of seven tetrapropoxycalix[4]arene derivatives
      immobilised in a 1,3-alternate conformation were determined using single-crystal
      X-ray crystallography. The cavity shapes of investigated derivatives (upper rim
      unsubstituted, distally di-substituted and tetra-substituted) and the nature of
      intermolecular interactions in molecular packing were compared. The results
      indicate that there are only two structural types adopted by basic
      tetrapropoxycalix[4]arene derivatives in the 1,3-alternate conformation.

PMID- 15999190
TI  - Multifunctional redox catalysts as selective enhancers of oxidative stress.
AB  - Certain cancer cells proliferate under conditions of oxidative stress (OS) and
      might therefore be selectively targeted by redox catalysts. Among these
      catalysts, compounds containing a chalcogen and a quinone redox centre are
      particularly well suited to respond to the presence of OS. These catalysts
      combine the specific electrochemical features of quinones and chalcogens. They
      exhibit high selectivity and efficiency against oxidatively stressed rat PC12,
      human Jurkat and human Daudi cells in cell culture, where their mode of action
      most likely involves the catalytic activation of existent and the generation of
      new reactive oxygen species. The high efficiency and selectivity shown by these
      catalysts makes them interesting for the development of anti-cancer drugs.

PMID- 15999191
TI  - A new approach to A,B-difunctionalisation of cyclodextrins using bulky 1,3
      bis[bis(aryl)chloromethyl]benzenes as capping reagents.
AB  - 1,3-Bis[bis(4-tert-butylphenyl)chloromethyl]benzene and 1,3-bis[bis(4
      anisyl)chloromethyl]benzene were employed as regioselective capping reagents for
      the preparation of C-6A,C-6B-bridged, permethylated alpha- and beta-CD
      derivatives; isolated yields up to 55% of proximally capped, methylated CDs were
      obtained, thus opening the way to the straightforward preparation of a wide range
      of A,B-functionalised CDs. As revealed by a single crystal X-ray diffraction
      study, the benzene-1,3-bis[bis(4-tert-butylphenyl)methyl] spacer is perfectly
      suited for A,B-capping of beta-cyclodextrin.

PMID- 15999192
TI  - Synthesis of profluorescent isoindoline nitroxides via palladium-catalysed Heck
      alkenylation.
AB  - The synthesis of a new structural class of isoindoline nitroxides (aminoxyls),
      accessible via the palladium-catalysed Heck reaction, is presented. Reaction of
      the aryl bromoamine, 5-bromo-1,1,3,3-tetramethylisoindoline (4) or dibromoamine,
      5,6-dibromo-1,1,3,3-tetramethylisoindoline (5) or the analogous bromonitroxides 6
      and 7 with methyl acrylate gives the acrylate substituted tetramethylisoindoline
      amines 8 and 10 and nitroxides 12 and 14. Similarly, the reaction of the aryl
      bromides and dibromides 4-7 with methyl 4-vinylbenzoate gives the carboxystyryl
      substituted tetramethylisoindoline amines 9 and 11 and the analogous nitroxides
      13 and 15. The carboxystyryl tetramethylisoindoline nitroxides demonstrate
      strongly suppressed fluorescence, which is revealed upon removal of the free
      radical by reduction or radical coupling.

PMID- 15999193
TI  - 3-Mercaptopropionic acid-nitrile imine adducts. An unprecedented cyclization into
      1,3,4-thiadiazol-2(3H)-ones and -2(3H)-thiones.
AB  - 3-Mercaptopropionic acid-nitrile imine acyclic adducts (6a-c) undergo
      cyclocondensation with 1,1'-carbonyldiimidazole to afford the respective 1,3,4
      thiadiazol-2-(3H)-ones (7a-c). Corresponding 1,3,4-thiadiazol-2(3H)-thiones (8a
      c) were likewise produced from 6a-cand 1,1'-thiocarbonyldiimidazole, with
      consequent elimination of the propionate moiety. The constitution of these
      heterocyclic products follows from analytical and spectral data and is confirmed
      by single crystal X-ray structure determination for 7b.

PMID- 15999194
TI  - Kinetics of oxidation of benzyl alcohols by the dication and radical cation of
      ABTS. Comparison with laccase-ABTS oxidations: an apparent paradox.
AB  - Laccase, a blue copper oxidase, in view of its moderate redox potential can
      oxidise only phenolic compounds by electron-transfer. However, in the presence of
      ABTS (2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) as a redox mediator,
      laccase reacts with the more difficult to oxidise non-phenolic substrates, such
      as benzyl alcohols. The role of ABTS in these mediated oxidations is
      investigated. Redox interaction with laccase could produce in situ two reactive
      intermediates from ABTS, namely ABTS++ or ABTS*+. These species have been
      independently generated by oxidation with Ce(iv) or Co(iii) salts, respectively,
      and their efficiency as monoelectronic oxidants tested in a kinetic study towards
      a series of non-phenolic substrates; a Marcus treatment is provided in the case
      of ABTS++. On these grounds, intervention of ABTS++ as a reactive intermediate in
      laccase-ABTS oxidations appears unlikely, because the experimental conditions
      under which ABTS++ is unambiguously generated, and survives long enough to serve
      as a diffusible mediator, are too harsh (2 M H2SO4 solution) and incompatible
      with the operation of the enzyme. Likewise, ABTS*+ seems an intermediate of
      limited importance in laccase-ABTS oxidations, because this weaker monoelectronic
      oxidant is unable to react directly with many of the non-phenolic substrates that
      laccase-ABTS can oxidise. To solve this paradox, it is alternatively suggested
      that degradation by-products of either ABTS++ or ABTS*+ are formed in situ by
      hydrolysis during the laccase-ABTS reactions, and may be responsible for the
      observed oxidation of non-phenolics.

PMID- 15999195
TI  - New opportunity for enzymatic modification of fats and oils with industrial
      potentials.
AB  - Novozym 435 (Candida antarctica lipase)-catalyzed glycerolysis of commercial oils
      and fats to produce monoglycerides (MGs) was investigated using a tetraammonium
      based ionic liquid (IL) as a reaction medium. A 90% yield of MGs and nearly 100%
      conversion of triglycerides in this ionic liquid were achieved, markedly higher
      than in normal solvents. The amphiphilic structure of cocosalkyl pentaethoxi
      methyl ammonium methosulfate (CPMA.MS) was suggested to be capable of creating a
      compatible system for glycerol, oils and fats, as well as inducing the shift of
      reaction equilibrium to the formation of MG. Interestingly, over a wide range of
      solvent dosage, the higher yields of MG were observed, indicating the good bulky
      substrate-tolerating capacity of the IL. The universal validity of the protocol
      was verified by being successfully applied to different commercial oils and fats.
      Excellent operational stability of the lipase and the reusability of IL were also
      observed in consecutive batchwise reactions. The results indicate that the
      protocol developed in this work provides a new environmentally benign "solution"
      to the enzymatic modification of fats and oils with industrial potentials.

PMID- 15999196
TI  - Spectroscopic and theoretical studies on intramolecular OH-pi hydrogen bonding in
      4-substituted 2-allylphenols.
AB  - 2-Allylphenol (1) constitutes a mixture of conformers, in which an OH-pi hydrogen
      bonded closed (1a) and open form (1b) can be distinguished. 4-Substituted 2
      allyphenols (2-9) have been synthesised and investigated by theoretical and
      spectroscopic methods. In 1-9, the energy and the structure of the hydrogen bonds
      show distinct variation with substituents. In the PE spectra of most compounds,
      two ionisations can be distinguished which are related to the allylic pi(C[double
      bond]C) orbitals of the two conformers a and b and differ in energy by
      DeltaIP(C[double bond]C). Alternatively, DeltaIP(C[double bond]C) can be
      determined indirectly from comparison of the PE spectra of the respective phenols
      and anisoles with the same substituents. DeltaIP(C[double bond, length as m
      dash]C) values between 0.3 and 1.1 eV were found. Frequency shifts Deltanu(OH) of
      the O-H vibration in CHCl3 solution were measured by IR spectroscopy. By means of
      correlation analysis of the relationship between the strength of the
      intramolecular hydrogen bond, DeltaIP(C[double bond]C), Deltanu(OH) values and
      substituent constants it is established how substituents in 4-position affect the
      intramolecular OH-pi hydrogen bond. The investigations demonstrate that the
      DeltaIP(C[double bond]C) data can be used as descriptors for this intramolecular
      interaction.

PMID- 15999197
TI  - Asymmetric syntheses of (-)-lentiginosine and an original pyrrolizidinic analogue
      thereof from a versatile epoxyamine intermediate.
AB  - Ready access to natural (-)-lentiginosine and its pyrrolizidinic analogue from a
      chiral vinylic epoxyamine in a straightforward five-step sequence is presented.
      Careful use of the RCM reaction on aminotriols and constitutes the key feature of
      the synthetic pathway. The alpha-amyloglucosidase inhibitory activities of the
      target compounds were evaluated and showed that the more easily accessible
      pyrrolizidinic analogue possesses an inhibitory activity quite similar to that of
      (-)-lentiginosine.

PMID- 15999198
TI  - Chiral receptors for phosphate ions.
AB  - The binding tendencies of the enantiomeric forms, R,R and S,S, of the neutral
      receptor 1 towards anions were investigated through UV-vis and 1H NMR titration
      experiments in DMSO. Both enantiomers form stable H-bond complexes with
      carboxylates and phosphates. In particular, receptor 1 strongly binds two H2PO4-
      ions according two stepwise equilibria, in which logK2 is higher than logK1. Such
      an unusual cooperativity effect is to be ascribed to the formation of strong H
      bond interactions between the two H2PO4- anions, when bound to the two urea
      subunits of the receptor, as demonstrated by the crystal and molecular structures
      of the 1 : 2 complex salt: [Bu4N]2[R,R-1...(H2PO4)2]. The S,S enantiomer forms an
      H-bond complex with the biologically relevant D-2,3-diphosphoglycerate anion,
      whose association constant is twice that of the R,R complex. Such an effect is
      ascribed to the different structural features of the two diastereomeric complexes
      in solution, as shown by 31P NMR studies.

PMID- 15999199
TI  - The synthesis and properties of bis-1,1'-(porphyrinyl)ferrocenes.
AB  - Ferrocene-bridged bisporphyrins have been synthesized by the condensation of
      corresponding dipyrromethane-derived diols with a bisdipyrromethane. Purification
      of the final compounds has been achieved without chromatography. The specific
      geometry of these bisporphyrins makes them valuable starting points for building
      complex molecular and supramolecular structures. In particular it provides a core
      to which multiple sites of attractive intermolecular interactions can be attached
      thereby creating compounds predisposed to form complex networks by association.
      We have studied the structure of bis-1,1'-(porphyrinyl)ferrocenes by 1H NMR, UV
      Vis and electrochemistry. Results have shown that complex dynamic processes occur
      in these molecules (which may involve conformers, formation of H-aggregates and
      tautomers) and that they have non-typical electrochemical behaviour.

PMID- 15999200
TI  - One-electron oxidation of [CCOCC]-* in the gas phase forms stable and decomposing
      forms of CCCCO.
AB  - The radical anion [CCOCC]-* may be made in the source of a VG ZAB 2HF mass
      spectrometer by the reaction between F-(from SF6) and (CH3)3SiC[triple
      bond]COC[triple bond]CSi(CH3)3. Vertical (Franck-Condon) one-electron oxidation
      of [CCOCC]-* in the first collision cell produces both singlet and triplet CCOCC.
      A combination of experiment and molecular modelling (at the CCSD(T)/aug-cc
      pVDZ//B3LYP/6-31G* level of theory) gives data which are consistent with the
      CCOCC neutrals rearranging over small barriers to form singlet and triplet CCCCO
      in exothermic reactions. Both singlet and triplet CCCCO formed in this way have
      excess energy. Singlet CCCCO has sufficient excess energy to effect decomposition
      exclusively to CCC and CO. In contrast, some of the triplet CCCCO neutrals are
      stable, while others decompose to CCC and CO.

PMID- 15999201
TI  - Highly enantioselective stereo-inverting sec-alkylsulfatase activity of
      hyperthermophilic Archaea.
AB  - rac-sec-Alkyl sulfate esters 1a-8a were resolved in low to excellent
      enantioselectivities with E-values up to >200 using whole cells of aerobically
      grown hyperthermophilic sulfur-metabolizers, such as Sulfolobus solfataricus DSM
      1617, Sulfolobus shibatae DSM 5389 and, most notably, Sulfolobus acidocaldarius
      DSM 639. Significantly enhanced selectivities were obtained using cells grown on
      sucrose-enriched Brock-medium. The stereochemical course of this biohydrolysis
      was shown to proceed with strict inversion of configuration, thus the preferred
      (R)-enantiomers were converted into the corresponding (S)-sec-alcohols to furnish
      a homochiral product mixture.

PMID- 15999202
TI  - Synthesis and biological evaluation of vinylogous combretastatin A-4 derivatives.
AB  - Stereospecific syntheses of the Z-E and E-Z vinylogues of combretastatin A-4, and
      two B-ring related analogues, were achieved through a Suzuki-Miyaura coupling. As
      compared to CA4, the derivative with a phenyl moiety has shown increased potency
      in its ability to inhibit tubulin polymerisation.

PMID- 15999203
TI  - Recognition of gene acceptor site based on multi-objective optimization.
AB  - A new method for predicting the gene acceptor site based on multi-objective
      optimization is introduced in this paper. The models for the acceptor, branch and
      distance between acceptor site and branch site were constructed according to the
      characteristics of the sequences from the exon-intron database and using common
      biological knowledge. The acceptor function, branch function and distance
      function were defined respectively, and the multi-objective optimization model
      was constructed to recognize the splice site. The test results show that the
      algorithm used in this study performs better than the SplicePredictor, which is
      one of the leading acceptor site detectors.

PMID- 15999204
TI  - BAF complex is closely related to and interacts with NF1/CTF and RNA polymerase
      II in gene transcriptional activation.
AB  - Brg- or hBrm-associated factor (BAF) complexes, a chromatin-remodeling complex
      family of mammalian cells, facilitate transcriptional activity by remodeling
      nucleosome structure. Brg1 is the core subunit of Brg-associated factor
      complexes. In the present study, we investigated the spatial relationship between
      Brg1 and nuclear factor 1 (NF1/CTF) and RNA polymerase II (RNAP II) upon gene
      transcriptional activation in vivo by employing immuno-gold labeling. The data
      showed that Brg1 was closely co-localized with NF1/CTF and RNAP II in HeLa cells.
      Moreover, the co-immunoprecipitation assay further revealed that Brg1 can be
      isolated together with NF1/CTF and RNAP II in the ConA-stimulated, but not the
      resting, T lymphocyte. The combined results suggested that BAF complexes can
      interact with NF1/CTF and RNAP II, and this interaction is closely dependent on
      the activation of gene transcription.

PMID- 15999205
TI  - Preparation and preliminary application of monoclonal antibodies against
      Trichokirin-S1, a small ribosome-inactivating peptide from the seeds of
      Trichosanthes kirilowii.
AB  - Trichokirin-S1, a small ribosome-inactivating peptide recently purified from the
      seeds of Trichosanthes kirilowii, has potential clinical applications because of
      its small molecular mass. Two stable strains of hybridomas (1F11 and 2A5) that
      can secrete highly specific monoclonal antibodies (mAbs) against Trichokirin-S1
      have been developed using the hybridoma technique. The isotypes of these two
      mAbs, 1F11 and 2A5, were determined to be IgG2a and IgG1, respectively. The
      affinity constants, which were measured by non-competitive ELISA, were found to
      be 2.3 x10(8) M(-1) and 2.8 x 10(8) M(-1), respectively. An immunoaffinity method
      using 2A5-coupled Sepharose 4B was successfully developed to purify Trichokirin
      S1. These two antibodies have also been used to detect Trichokirin-S1 in Western
      blot.

PMID- 15999206
TI  - Substitutions of the conserved Gly47 affect the CF1 inhibitor and proton gate
      functions of the chloroplast ATP synthase epsilon subunit.
AB  - The conserved residue Gly47 of the chloroplast ATP synthase beta subunit was
      substituted with Leu, Arg, Ala and Glu by site-directed mutagenesis. This process
      generated the mutants epsilon G47L, epsilon G47R, epsilon G47A and epsilon G47E,
      respectively. All the beta variants showed lower inhibitory effects on the
      soluble CF1(-epsilon) Ca2+-ATPase compared with wild-type epsilon. In reduced
      conditions, epsilon G47E and epsilon G47R had a lower inhibitory effect on the
      oxidized CF1(-epsilon) Ca2+-ATPase compared with wild-type epsilon. In contrast,
      epsilon G47L and epsilon G47A increased the Ca2+-ATPase activity of soluble
      oxidized CF1(-epsilon). The replacement of Gly47 significantly impaired the
      interaction between the subunit epsilon and gamma in an in vitro binding assay?
      Further study showed that all epsilon variants were more effective in blocking
      proton leakage from the thylakoid membranes. This enhanced ATP synthesis of the
      chloroplast and restored ATP synthesis activity of the reconstituted membranes to
      a level that was more efficient than that achieved by wild-type epsilon. These
      results indicate that the conserved Gly47 residue of the epsilon subunit is very
      important for maintaining the structure and function of the epsilon subunit and
      may affect the interaction between the epsilon subunit, beta subunit of CF1 and
      subunit III of CFo, thereby regulating the ATP hydrolysis and synthesis, as well
      as the proton translocation role of the subunit III of CFo.

PMID- 15999207
TI  - cDNA array analysis of the differential expression change in virulence-related
      genes during the development of resistance in Candida albicans.
AB  - Candida albicans is the most frequently isolated fungus in immunocompromised
      patients associated with mucosal and deep-tissue infections. To investigate the
      correlation between virulence and resistance on a gene expression profile in C.
      albicans, we examined the changes in virulence-related genes during the
      development of resistance in C. albicans from bone marrow transplant patients
      using a constructed cDNA array representing 3096 unigenes. In addition to the
      genes known to be associated with azole resistance, 16 virulence-related genes
      were identified, whose differential expressions were newly found to be associated
      with the resistant phenotype. Differential expressions for these genes were
      confirmed by RT-PCR independently. Furthermore, the up-regulation of EFG1, CPH2,
      TEC1, CDC24, SAP10, ALS9, SNF1, SPO72 and BDF1, and the down-regulation of RAD32,
      IPF3636 and UBI4 resulted in stronger virulence and invasiveness in the resistant
      isolates compared with susceptible ones. These findings provide a link between
      the expression of virulence genes and development of resistance during C.
      albicans infection in bone marrow transplant (BMT) patients, where C. albicans
      induces hyphal formation and expression change in multiple virulence factors.

PMID- 15999208
TI  - Sequence analysis and structural prediction of the severe acute respiratory
      syndrome coronavirus nsp5.
AB  - The non-structural proteins (nsp or replicase proteins) of coronaviruses are
      relatively conserved and can be effective targets for drugs. Few studies have
      been conducted into the function of the severe acute respiratory syndrome
      coronavirus (SARS-CoV) nsp5. In this study, bioinformatics methods were employed
      to predict the secondary structure and construct 3-D models of the SARS-CoV GD
      strain nsp5. Sequencing and sequential comparison was performed to analyze the
      mutation trend of the polymerase nsp5 gene during the epidemic process using a
      nucleotide-nucleotide basic local alignment search tool (BLASTN) and a protein
      protein basic local alignment search tool (BLASTP). The results indicated that
      the nsp5 gene was steady during the epidemic process and the protein was
      homologous with other coronavirus nsp5 proteins. The protein encoded by the nsp5
      gene was expressed in COS-7 cells and analyzed by sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). This study provided the foundation
      for further exploration of the protein's biological function, and contributed to
      the search for anti-SARS-CoV drugs.

PMID- 15999209
TI  - Efficient differentiation of embryonic stem cells into neurons in glial cell
      conditioned medium under attaching conditions.
AB  - Embryonic stem (ES) cells can differentiate into neurons in vitro, which provides
      hope for the treatment of some neurodegenerative diseases through cell
      transplantation. However, it remains a challenge to efficiently induce ES cells
      to differentiate into neurons. Here, we show that murine ES cells can efficiently
      differentiate into neurons when cultured in glial cell-conditioned medium (GCM)
      under attaching conditions without the formation of embryoid bodies. In
      comparison with murine embryonic fibroblast-conditioned medium, we found that GCM
      has a positive effect on limiting the generation of non-neuronal cells, such as
      astrocytes. In addition, compared with suspension conditions, attaching
      conditions delay the differentiation process of ES cells.

PMID- 15999210
TI  - ZnPcS2P2-based photodynamic therapy induces mitochondria-dependent apoptosis in
      K562 cells.
AB  - Mitochondria play a key role in the regulation of apoptosis induced by numerous
      antitumor chemotherapeutic and other toxic agents. Photodynamic therapy (PDT)
      exerts significant cellular killing efficacy through either an apoptotic or
      necrotic cell death pathway. This study investigated the mechanism underlying the
      killing effects of a novel amphipathic photosensitizer [di-sulfonated di
      phthalimidomethyl phthalocyanine zinc (ZnPcS2P2)]-mediated photodynamic therapy
      (ZnPcS2P2-PDT) on K562 cells. Apoptosis was evident in the post-PDT cells through
      the TdT-mediated dUTP nick end labeling (TUNEL) method and DNA fragmentation
      assay. After ZnPcS2P2-PDT, K562 cells underwent mitochondria-dependent apoptosis
      as evidenced by the release of cytochrome c from mitochondria into cytosol,
      accompanied by mitochondrial membrane potential (deltapsim) reduction, indicating
      the opening of the mitochondrial permeability transition pore (PTP). The
      activities of protease from the caspase family and caspase-3 were also
      significantly elevated. Furthermore, ZnPcS2P2-PDT down-regulated the expression
      of chimaeric Bcr-Abl oncoprotein, which is the molecular hallmark of chronic
      myelogenous leukemia (CML).

PMID- 15999211
TI  - A new combination of mutated loxPs in a vector for construction of phage antibody
      libraries.
AB  - In the construction of large antibody libraries by in vivo recombination, two non
      homogeneous loxP sites are required for the exchange of V genes between phagemids
      to create many new VH-VL combinations. The mutated loxP511 was designed not to
      recombine with the wild-type loxP (loxPwt) in early studies and a combination of
      the two has been used to construct antibody libraries. But recent reports have
      shown that recombination occurs between loxPwt and loxP511. This suggests that
      the combinational use of loxP511 and loxPwt might lead to the loss of the V gene
      diversity of antibody libraries. Therefore, it is necessary to find a new
      combination of loxPs to avoid the excision recombination in the antibody library.
      In this study, we found that the excision recombination between loxP511 and
      loxP2272, another mutated loxP sequence, was undetectable within one phagemid,
      while the excision recombination between loxP511 and loxPwt occurred at a
      frequency of 40%, higher than that reported previously. Furthermore, the in vivo
      recombination of different phagemids with loxP511 and loxP2272 showed that the V
      gene exchange was efficiently mediated to produce new VH-VL combinations. It was
      concluded that the loxP511 and loxP2272 combination was more favorable for
      reducing the excision recombination and constructing large phage antibody
      libraries with high diversity.

PMID- 15999212
TI  - Heat shock protein 90 indirectly regulates ERK activity by affecting Raf protein
      metabolism.
AB  - Extracellular signal-regulated protein kinase (ERK) has been implicated in the
      pathogenesis of several nerve system diseases. As more and more kinases have been
      discovered to be the client proteins of the molecular chaperone Hsp90, the use of
      Hsp90 inhibitors to reduce abnormal kinase activity is a new treatment strategy
      for nerve system diseases. This study investigated the regulation of the ERK
      pathway by Hsp90. We showed that Hsp90 inhibitors reduce ERK phosphorylation
      without affecting the total ERK protein level. Further investigation showed that
      Raf, the upstream kinase in the Ras-Raf-MEK-ERK pathway, forms a complex with
      Hsp90 and Hsp70. Treating cells with Hsp90 inhibitors facilitates Raf
      degradation, thereby down-regulating the activity of ERK.

PMID- 15999213
TI  - Accuracy of computed tomography and magnetic resonance imaging in the detection
      of lymph node involvement in cervix carcinoma.
AB  - Lymphnodes status in cervical carcinoma is important in therapeutic planning, and
      the role of Computed Tomography (CT) and Magnetic Resonance (MR) is
      controversial: this paper aims to evaluate their accuracy in diagnosing nodal
      metastases in patients with cervical carcinoma. We reviewed, retrospectively and
      blindly, CT and MR of 62 patients, before surgical lymphnode resection: 45 of
      these patients had pre-surgical chemotherapy. Lymphnodes were defined metastatic
      by CT and MRI when larger than 1 cm short axis. Both diagnoses by the original
      routine reports and by a second blind expert were compared with pathological
      reports. RESULTS: combining the reading results of both observers CT showed a
      sensitivity of 64.6% and specificity of 93.3%; MRI a sensitivity of 72.9% and
      specificity of 93.1%. Positive Predictive Value was 50.8% for CT and 53% for MR,
      while Negative Predictive Value was 96% both for CT and MR. The expert
      Radiologist reviewing the films obtained better results. Inter-observer
      variability in the lower quadrants was high for each imaging technique (kappa for
      CT: 0.71; kappa for MRI: 0.84). Both imaging techniques showed similar screening
      accuracy in identifying nodal metastases. The radiologist's experience is
      important in determining the performance of the imaging technique. Anyway, CT and
      MRI are only moderately sensitive for detection of nodal metastases and the
      clinical impact of their results in patient's management is limited.

PMID- 15999214
TI  - Pain experience during internal spermatic vein embolization for varicocele:
      comparison of two cyanoacrylate glues.
AB  - The purpose of this study was to evaluate possible pain sensation differences in
      patients after retrograde varicocele embolization either with n-butyl-(2)
      cyanoacrylate (NBCA) or with n-butyl-(2)-cyanoacrylate + methacryloxysulfolane
      (NBCA-MS). Transcatheter varicocele embolization was performed in 64 consecutive
      patients (62 left, two bilateral). Embolization was done with NBCA (n=32) or NBCA
      MS (n=32). Immediately after the procedure, patients were asked to evaluate pain
      during embolization using a visual analog scale (VAS). Statistical analysis was
      done with Student's t test. Mean pain score on VAS was 3.23 (range: 0-8) for NBCA
      and 3.28 (range 0-9) for NBCA-MS. This difference was not significant (P=0.932).
      Independently of the type of glue, no difference in pain sensation (P value
      0.421) was found between patients younger than 18 (n=29) and patients older than
      18 years of age (n=35) (younger than18, mean 3.52; older than 18, mean 3.05). No
      difference in mean pain experience level (P=0.323) was seen in 11 patients with
      vessel wall perforation (23.4%) during the procedure (3.89; range: 0-8.5) in
      comparison with those without perforation (mean pain sensation level: 3.13;
      range: 0-9). No difference in pain experience was found after transcatheter
      varicocele embolization either with NBCA or NBCA-MS. Age and vessel wall
      perforation have no influence on pain sensation independently of the type of
      glue.

PMID- 15999215
TI  - Pineapple juice labeled with gadolinium: a convenient oral contrast for magnetic
      resonance cholangiopancreatography.
AB  - The aim of our study was to prepare in vitro a pineapple juice (PJ) solution
      labeled with a minimal gadolinium concentration working as a negative contrast
      agent in heavily T2-weighted imaging and to assess that solution in vivo as a
      negative oral contrast agent for magnetic resonance cholangiopancreatography
      (MRCP). Three PJs were compared in vitro according to their T2. Increasing
      concentrations of gadolinium (Gd)-DOTA in PJ were assessed in vitro for T2
      reduction. Single-shot turbo spin echo T2-weighted MR cholangiopancreatograms
      were obtained for 35 patients with suspected biliopancreatic duct disease, before
      and after ingestion of the PJ/Gd-DOTA solution. Signal intensity (SI)
      measurements of gastroduodenal lumens, pancreatobiliary ducts, and image quality
      scores were obtained systematically before and after contrast ingestion. The in
      vitro selected Gd-DOTA concentration in the PJ was 2.76 mmol/l. Ingestion of 180
      ml of PJ labeled with 1 ml of Gd-DOTA eliminated efficiently the gastroduodenal
      SI in MRCP, improving significantly the rates of complete visualization of the
      pancreatobiliary ducts (P<0.01) and the MRCP image quality scores (P<0.05). All
      patients easily ingested the contrast solution and found the solution palatable.
      PJ labeled with gadolinium constituted an efficient and convenient negative oral
      contrast agent for MRCP.

PMID- 15999216
TI  - Continence pads: have we got it right?
AB  - Women listed in the Croydon Community Continence database were contacted with a
      self-assessment questionnaire regarding continence pad usage and quality of life.
      Completed questionnaires were received from 763 of 1509 (51%) participants. Pads
      were used for bladder dysfunction (88.1%) and bowel dysfunction (44%). The
      majority (82.5%) had concurrent medical disorders and problems with mobility with
      77.5% being on one or more types of medication. Nearly 39% of women claimed that
      they would be happy to continue pad use indefinitely and only 28% expressed
      interest in seeking further help. Compared to bowel dysfunction, bladder
      dysfunction appeared to have a greater impact on women's quality of life (P <
      0.001). Containment products make a substantial contribution in improving the
      quality of lives of women with bowel and bladder dysfunction. The financial
      burden of containment products has a major impact on the health budget and
      therefore, comprehensive clinical evaluation should be mandatory before
      relegating women to pads as a final resort.

PMID- 15999217
TI  - Dose response with darifenacin, a novel once-daily M3 selective receptor
      antagonist for the treatment of overactive bladder: results of a fixed dose
      study.
AB  - This study evaluated the efficacy, tolerability, and safety of darifenacin, an M3
      selective receptor antagonist (M3 SRA), in patients with overactive bladder
      (OAB). In a multicenter, double-blind, placebo-controlled dose-ranging study, 439
      adult OAB patients (85.4% female) were randomized to darifenacin controlled
      release tablets 7.5 mg (n = 108), 15 mg (n = 107) or 30 mg (n = 115) qd, or
      placebo (n = 109) for 12 weeks. Darifenacin significantly reduced the median
      number of incontinence episodes/week (-68.7, -76.5, and -77.3% from baseline at
      7.5, 15, and 30 mg, respectively, vs -46% with placebo, all p < 0.01) and dose
      relatedly improved micturition frequency, frequency and severity of urgency,
      nocturia, and bladder capacity. Darifenacin was well tolerated. Adverse events
      were commonly mild to moderate dry mouth and constipation. There were no safety
      concerns. Darifenacin is effective and well tolerated in the treatment of OAB,
      with 7.5 and 15 mg doses offering flexibility of dosing for optimal treatment
      outcome.

PMID- 15999218
TI  - The arteries of the humeral head and their relevance in fracture treatment.
AB  - Bone vascularisation has gained increased interest in relation to the blood
      supply of bone fragments during treatment of fractures. In the current study the
      pattern of vascular supply of the proximal humerus was studied in six cadavers by
      the corrosion technique. Furthermore, the effect of fractures on the vascular
      supply was also investigated. In all preparations the intraosseous arteries of
      the humeral head arose from the circumflex arteries, which surrounded the humerus
      and dispatched branches towards the proximal end. The main vessel was the branch
      of the anterior circumflex artery, penetrating the major tubercle in six of six
      cases. Due to the intraosseous arch shape of this vessel it is referred to as the
      arcuate artery. Besides other smaller vessels, there was also a vascular network
      arising from the posterior circumflex artery. Their branches penetrated medially
      at the cartilage bone interface in five of six preparations. The medial bone
      arteries appear to gain distinctive importance in humeral head fractures by their
      impact on the vascularisation of the fracture fragments. After disruption of the
      arterial supply from the arcuate artery, the vascularisation of the head
      fragments is most likely ensured by this group of vessels. Therefore, necessary
      repositioning manoeuvres during open reduction of the fracture should be
      conducted with care in order to preserve these arteries.

PMID- 15999219
TI  - Treatment of primary inguinal hernias by "held in mesh repair": our experience
      related to 3,520 cases.
AB  - In the last 15 years, a rapid evolution occurred from the traditional
      hernioplasties toward prosthetic techniques, in Italy. Outpatient procedures
      under local anaesthesia are now most commonly performed. We report our experience
      with a personal modification of the sutureless mesh repair, called "held in mesh
      repair". From 1990 to 2003 we treated 3,520 cases of primary hernia with the
      "held in mesh repair". 2,370 patients were affected by a unilateral hernia and
      575 by a bilateral one. Local anaesthesia was used in 92% of the cases, loco
      regional in 6% and general in 2%. Sixteen (0.4%) hernias recurred after 2 years,
      while two further recurrences (total 0.5%) were observed after 3 years; three
      femoral pseudo-relapses (0.08%) occurred before the first postoperative year. An
      overall incidence of 1.3% of major complications were observed. One mortality
      case (0.02%) occurred 3 days after the operation for cardiovascular
      complications. The favourable results of the "held in mesh repair" and the
      simplicity of the procedure suggest that it can be considered a safe and reliable
      technique for most primary inguinal hernias.

PMID- 15999220
TI  - The femoral nerve in the repair of inguinal hernia: well worth remembering.
AB  - Injury to the nerves after inguinal hernia surgery is uncommon. The femoral nerve
      may be damaged by suture or staples, tissue scar entrapment, local anesthesia
      blockade or direct compression. We present a case of a transient lesion of the
      femoral nerve after mesh hernioplasty for a re-recurrent inguinal hernia,
      confirmed by radiological studies, electrophysiology and clinical recovery. The
      diagnosis, mechanism of injury and surgical approach are reviewed. Surgery to a
      recurrent hernia may be underestimated. The role of electromyography nerve
      conducting studies is emphasized insisting on the importance of clinical
      evolution for the successful management of these infrequent injuries.

PMID- 15999221
TI  - Improved thermal stability and activity in the cold-adapted lipase B from Candida
      antarctica following chemical modification with oxidized polysaccharides.
AB  - In order to improve the thermal stability (t(1/2)) and activity of lipase B from
      cold-adapted Candida antarctica (CALB), amino groups of the enzyme were
      chemically linked to a range of oxidized polysaccharides using a range of
      reducing agents. By chemically modifying CALB using 0.1% dextran (250 kDa) at pH
      8.6 for 10 days using borane-pyridine complex as reducing agent, increased
      thermal stability (t(1/2), 168 min at 70 degrees C) and activity (65% higher
      specific activity) was achieved compared to the unmodified enzyme (t(1/2), 18 min
      at 70 degrees C). Improvements in thermostability were generally better with high
      molecular weight polymers such as dextran (40 and 250 kDa) or ficoll (70 and 400
      kDa) in comparison to low molecular weight inulin (5 kDa). The shape of the
      polymer also appeared to be important with elongated, elipsoidal-shaped dextran
      providing better thermostabilization than spherical-shaped ficoll. Borane
      pyridine complex was found to be a good, non-toxic reducing agent for improving
      thermostability, compared with sodium borohydride and sodium cyanoborohydride. An
      interesting finding was that, in all cases, specific activity of the modified
      enzymes increased with a concomitant increase in thermostability. This response
      defies the general principle of a trade-off between activity and stability, and
      demonstrates that chemical modification provides new avenues for improving the
      thermal stability of enzymes from psychrophiles without sacrificing their
      activity.

PMID- 15999222
TI  - Degradation of crude oil by an arctic microbial consortium.
AB  - The ability of a psychrotolerant microbial consortium to degrade crude oil at low
      temperatures was investigated. The enriched arctic microbial community was also
      tested for its ability to utilize various hydrocarbons, such as long-chain
      alkanes (n-C24 to n-C34), pristane, (methyl-)naphthalenes, and xylenes, as sole
      carbon and energy sources. Except for o-xylene and methylnaphthalenes, all tested
      compounds were metabolized under conditions that are typical for contaminated
      marine liquid sites, namely at pH 6-9 and at 4-27 degrees C. By applying
      molecular biological techniques (16S rDNA sequencing, DGGE) nine strains could be
      identified in the consortium. Five of these strains could be isolated in pure
      cultures. The involved strains were closely related to the following genera:
      Pseudoalteromonas (two species), Pseudomonas (two species), Shewanella (two
      species), Marinobacter (one species), Psychrobacter (one species), and Agreia
      (one species). Interestingly, the five isolated strains in different combinations
      were unable to degrade crude oil or its components significantly, indicating the
      importance of the four unculturable microorganisms in the degradation of single
      or of complex mixtures of hydrocarbons. The obtained mixed culture showed obvious
      advantages including stability of the consortium, wide range adaptability for
      crude oil degradation, and strong degradation ability of crude oil.

PMID- 15999223
TI  - Sequence of the gene for a high-alkaline mannanase from an alkaliphilic Bacillus
      sp. strain JAMB-750, its expression in Bacillus subtilis and characterization of
      the recombinant enzyme.
AB  - A novel alkaline mannanase Man26A has been found in the culture of an
      alkaliphilic Bacillus sp. strain JAMB-750 and the optimal pH for the mannanase
      activity of the enzyme was around pH 10 (J Biol Macromol 4: 67-74, 2004). This
      optimal pH is the highest among those of the mannanases reported to date. The
      gene man26A coding the enzyme was cloned from the genomic DNA of strain JAMB-750
      and sequenced. It encodes a protein of 997 amino acids including a signal
      peptide. The N-terminal half (Glu27-Val486) of the enzyme exhibited moderate
      similarities to other mannanases belonging to glycoside hydrolase family 26, such
      as the enzymes from Cellvibrio japonicus (37% identity), Cellulomonas fimi (33%
      identity), and Bacillus sp. strain AM-001 (28% identity). The C-terminal half was
      found to contain four domains. The first, second, third, and fourth domains
      exhibited similarities to the carbohydrate-binding module, the mannan-binding
      module, the Homo sapiens collagen type IX alpha I chain, and the membrane anchor
      region of Gram-positive surface proteins, respectively. Its recombinant mannanase
      was produced extracellularly using Bacillus subtilis as the host. The optimal pH
      for the mannanase activity of the recombinant enzyme was around pH 10. The enzyme
      was very resistant to surfactants, for example, SDS up to 2.0% (w/v).

PMID- 15999224
TI  - A hyperthermophilic laccase from Thermus thermophilus HB27.
AB  - A copper-inducible laccase activity was detected in Thermus thermophilus HB27.
      The enzyme was partially purified and separated by SDS-PAGE. After staining, a
      gel slice containing a approximately 53-kDa protein was excised and treated with
      trypsin, and the in-gel digests were analyzed by mass spectrometry. By mass
      fingerprinting, the peptides were found to share identity with the TTC1370
      protein of the thermophile, which was tentatively annotated as a laccase in the
      whole genome analysis, albeit experimental evidence was lacking. The assigned
      mass nearest to the N-terminal sequence was that from Gln23 to Lys31. By signal
      peptide prediction, TTC1370 protein was assumed to be a secretory protein
      starting from Gln23. The DNA encoding the mature protein was then cloned and
      expressed in Escherichia coli. The recombinant enzyme, expressed as an
      apoprotein, was dialyzed against copper-containing buffer to yield a holoprotein.
      The holoprotein was purified to homogeneity, which displayed a blue color typical
      of laccases and oxidized canonical laccase substrates such as guaiacol and 2,2'
      azino-bis(3-ethylbenzthiazoline-6-sulfonate). The enzyme was most notable for its
      striking thermophilicity; the optimal reaction temperature was approximately 92
      degrees C and the half-life of thermal inactivation at 80 degrees C was >14 h,
      ranking it as the most thermophilic laccase reported thus far.

PMID- 15999225
TI  - Transcriptome expression profiles in prenatal pigs in relation to myogenesis.
AB  - Myogenesis, the formation of muscle fibers, is a complex process. Pigs have been
      selected for efficient muscle growth for the past decades making them interesting
      to study myogenesis. We studied expression profiles of genes known to affect
      myogenesis, muscle structural proteins, and energy metabolism in prenatal pigs
      from 14 to 91 days of gestation. Primary and secondary muscle fiber formation
      takes place during days 30-60 and 54-90 of gestation, respectively. Differential
      expression and expression levels of the genes were studied using microarray
      technology. Gene activation and repression profiles were studied counting the
      number of spots with detectable signal. The number of spots for muscle tissue
      structural protein genes showing upregulated expression increased constantly from
      day 14 until day 91 of gestation indicating continued activation of genes during
      this period. The mRNA expression level of the genes showed a peak around day 35
      of gestation. The expression levels of genes affecting myogenic differentiation
      (stimulating and inhibiting) showed a peak at day 35 of gestation. The number of
      spots for differentiation-stimulating genes showing differential expression
      reaches a first peak around day 35 of gestation and a nadir at day 49 of
      gestation while the number of spots for differentiation-inhibiting genes reaches
      a nadir at day 35 of gestation. Myogenic differentiation seems less a matter of
      the expression level of genes affecting differentiation, but depends on the
      balance between the number of significantly activated genes for stimulating and
      inhibiting differentiation. Genes stimulating myoblast proliferation showed a
      small peak expression prior to day 35 of gestation indicating myoblast
      proliferation before differentiation. The number of spots and the expression
      levels of genes for glycolysis and ATP-metabolism are at a nadir around days 35
      and 49-63 of gestation suggesting that the energy metabolism is low during fusion
      of myoblasts into multinucleated muscle fibers.

PMID- 15999226
TI  - Alterations in the proportions of skeletal muscle proteins following a unilateral
      lesion to the substantia nigra pars compacta of rats.
AB  - It is well established that mammalian skeletal muscles exhibit a considerable
      degree of plasticity and one of the main determining factors of this plasticity
      is the activity pattern and duration of motoneurone discharge. Lesions to the
      right substantia nigra pars compacta (SNpc) of six adult rats were made to
      determine whether altered output from the SNpc ultimately leads to a change in
      the expression of proteins in contralateral skeletal muscles. After 4 months,
      altered motor performance was identified by the administration of amphetamine.
      After 7 months, 30-70% of dopaminergic cells in the SNpc had been destroyed. The
      protein content of muscles was then quantified from densitometric scans of gels,
      and expressed as a % of the amount of actin (the protein used as a reference in
      this study). The lesion affected the expression of different protein isoforms in
      the fast- and slow-twitch muscles. In slow-twitch soleus muscles, the lesion
      decreased the proportion of alpha-tropomyosin and increased the proportion of
      beta-tropomyosin. In the fast-twitch extensor digitorum longus muscles, the
      lesion increased the proportion of the fast isoform of troponin-T1f, and
      decreased the proportions of the two isoforms of myosin light chain. This study
      establishes a connection between the chronic effects of a lesion to the SNpc,
      with a loss of dopaminergic neurones, impaired motor performance, and altered
      expression of proteins in skeletal muscle. The implication of these results is
      that the altered motor function observed in Parkinson's disease may be associated
      with alterations to the expression of skeletal muscle proteins.

PMID- 15999227
TI  - Localization of myosin phosphatase target subunit and its mutants.
AB  - Transient transfection of NIH3T3 cells with various constructs of myosin
      phosphatase target subunit (MYPT1) and GFP showed distinct cellular
      localizations. Constructs containing the N-terminal nuclear localization signals
      (NLS), i.e. full-length MYPT1 and N-terminal MYPT1 fragments, were concentrated
      in the nucleus. Full-length chicken and human MYPT1-GFP showed discrete nuclear
      foci. Deletion of the N-terminal NLS or use of central or C-terminal MYPT1
      fragments did not show unique nuclear distributions (C-terminal NLS are present).
      Transient transfection of NIH3T3 cells (in the presence of serum) with full
      length MYPT1-GFP caused a marked decrease in number of attached cells, an
      apparent block in the cell cycle prior to M phase and signs of increased
      apoptosis. Under conditions of serum starvation the unique nuclear localization
      of MYPT1-GFP was not found and there was no marked decrease in the number of
      attached cells (after 48 h). Stable transfection of HEK 293 cells with GFP-MYPT1
      was obtained. MYPT1 and its N-terminal mutants bound to retinoblastoma protein
      (Rb), raising the possibility that Rb is implicated in the effects caused by
      overexpression of MYPT1.

PMID- 15999228
TI  - Auto-oscillations of skinned myocardium correlating with heartbeat.
AB  - Skinned myocardium (or myofibrils) exhibits auto-oscillations of sarcomere length
      and developed force called SPOC (SPontaneousOscillatoryContraction) under partial
      activation conditions. In SPOC, each sarcomere repeats the cycle of slow
      shortening and rapid lengthening, and the lengthening phase propagates
      sequentially to the adjacent sarcomeres in waves (SPOC wave). In this study, we
      analyzed the sarcomeric oscillation in SPOC in skinned myocardium of various
      animal species (rat, rabbit, dog, pig, and cow) with different heart rates. The
      period of oscillation, the sarcomere shortening velocity, and the velocity of
      SPOC wave, strongly correlated with the resting heart rate of the animal species.
      The shortening velocity in particular was proportional to the resting heart rate.
      We then examined the motile activity of each cardiac myosin by an in vitro
      motility assay. The sliding velocity of actin filaments, which is an index of the
      motile activity of myosin, also correlated with the resting heart rate but the
      relationship was not proportional. As a result, the ratio of sarcomere shortening
      velocity in SPOC to the sliding velocity of actin filaments was not constant but
      became higher with a higher heart rate. This suggests that the sarcomere
      shortening velocity in SPOC is modulated by some additional factors besides the
      motile activity of myosin, resulting in the proportional relationship between the
      shortening velocity of the sarcomere and the resting heart rate.

PMID- 15999229
TI  - Kinematic evaluation in Parkinson's disease using a hand-held position transducer
      and computerized signal analysis.
AB  - BACKGROUND: The objective of this work was to develop a device for quantification
      of akinesia in Parkinson's disease, for the use in home monitoring of PD
      patients, as a part of home telecare programs. For this purpose a simple movement
      task is to be preferred, and the measurement devices must be small, lightweight,
      and easy to use, so patients may perform the measurements unattended. Another
      intended application was optimisation of the electrode position during
      implantations of neuromodulation systems for treatment of Parkinson. METHOD: A
      hand held transducer was used to measure the position of the thumb while the
      patient repeatedly flexed and extended the thumb. The position data was sampled
      and stored on a personal computer with a plug in converter card and software.
      Measurements were performed on 15 PD patients and 6 age-matched controls. Signal
      analysis procedures were developed in order to automatically derive numerical
      parameters that quantify the movement performance. In order to select the most
      relevant parameters, they were correlated to Unified Parkinson Disease Rating
      Scale (UPDRS) motor scores (Spearman's rank, single sided, p < 0.05). FINDINGS:
      In reviews of the raw position signals the amplitude and frequency was found to
      be lower in patients than in controls. In patients the movement was frequently
      interrupted by short periods of hesitation. The calculated parameters of covered
      distance (correlation coefficient r = -0.63), hesitation (r = 0.64) and frequency
      (r = -0.6) were found to be most relevant, as they correlated best to the UPDRS
      hand pronation/supination score. DISCUSSION: The equipment proved to be fast to
      setup and easy to use. The signal analysis methods provided meaningful numerical
      parameters for quantification of akinesia, represented in hand
      pronation/supination. These results suggest that the described methods may be
      useful for telemedicine and intraoperative use.

PMID- 15999230
TI  - A thin-film equation for viscoelastic liquids of Jeffreys type.
AB  - We derive a novel thin-film equation for linear viscoelastic media describable by
      generalized Maxwell or Jeffreys models. As a first application of this equation
      we discuss the shape of a liquid rim near a dewetting front. Although the
      dynamics of the liquid is equivalent to that of a phenomenological model recently
      proposed by Herminghaus et al. (S. Herminghaus, R. Seemann, K. Jacobs, Phys. Rev.
      Lett. 89, 056101 (2002)), the liquid rim profile in our model always shows
      oscillatory behaviour, contrary to that obtained in the former. This difference
      in behaviour is attributed to a different treatment of slip in both models.

PMID- 15999231
TI  - Commentary on "A prospective trial of mechanical physiotherapy for lumbar disk
      prolapse" by D. Broetz et al. in J Neurol (2003) 250 : 746-749.

PMID- 15999232
TI  - Increased incidence of jugular valve insufficiency in patients with transient
      global amnesia.
AB  - OBJECTIVE: While transient global amnesia (TGA) is a clinically well defined
      disorder, its etiology is poorly understood. Cerebral venous hypertension and
      subsequent damage to hippocampal and diencephalic structures are among the
      discussed hypothetical causes. Using a direct method for the study of retrograde
      flow during a Valsalva maneuver, we determined whether jugular valve
      insufficiency contributes to cerebral venous hypertension in patients with TGA.
      METHODS: Jugular valve closure was assessed by duplex sonography in 20 patients
      with TGA and 20 age and gender matched controls. The diagnosis of valvular
      insufficiency was made on the basis of recently established criteria. RESULTS:
      Valvular insufficiency (either left or right-sided, or bilateral) was identified
      in 85% of patients with TGA,and in 45% of controls (p = 0.008). All patients with
      involuntary Valsalva episodes immediately prior to TGA developed valvular
      insufficiency (n = 8; p = 0.13 compared with patients who did not recall such an
      event). The mean duration of the insufficiency jet did not differ significantly
      between patients with TGA (3.26 s) and controls (2.78 s; p = 0.315). However,
      patients with TGA who experienced a trigger event were characterized by
      significantly longer insufficiency reflux times (3.84 s) than those without (2.55
      s; p = 0.03). CONCLUSIONS: TGA is associated with an increase in the prevalence
      of jugular insufficiency. Valvular insufficiency may lead to increased venous
      pressure transmission during a Valsalva maneuver and thus contribute to venous
      ischemia in TGA. The association of valvular insufficiency and longer reflux
      times with the occurrence of a trigger event further suggests that cerebral
      venous congestion is an important etiological factor in transient global amnesia.

PMID- 15999233
TI  - Spinocerebellar ataxia type 4. Investigation of 34 candidate genes.
AB  - The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a
      clinically and genetically heterogeneous group of neurodegenerative disorders. To
      date 24 different loci have been identified for these conditions. A locus at
      chromosome 16q22.1 co-segregates with the disease phenotype in families of
      Scandinavian, Japanese and German origin. The corresponding SCA4 locus was
      narrowed down to 7.94 Mb for the two European and to 1.25 Mb for Japanese
      pedigrees. Unfortunately, because of the phenotypic differences between patients
      from Japan and Europe it is not possible to decide if SCA families linked to
      chromosome 16q22.1 share a common disease genotype or not. To look for mutations
      in the German family we screened 34 candidate genes in a 3.69 cM region. With the
      exception of two cSNPs, no segregation of DNA variations with the disease
      phenotype was found.

PMID- 15999235
TI  - G. B. A. Duchenne de Boulogne (1806-1875).

PMID- 15999234
TI  - Psychotic symptoms in Parkinson's disease. From description to etiology.
AB  - Psychotic symptoms are common in Parkinson's disease (PD) and occur in at least
      20% of medication-treated patients. Benign visual hallucinations usually appear
      earlier, while malignant hallucinations, confusional states, delusions, paranoid
      beliefs, agitation, and delirium become more frequent with disease progression.
      Virtually all antiparkinsonian drugs may produce psychotic symptoms. Cognitive
      impairment, increased age, disease duration and severity, depression, and sleep
      disorders have been consistently identified as independent risk factors for their
      development. Although the precise pathoetiologic mechanisms remain unknown, we
      review evidence that links ventral dopaminergic pathway dysfunction
      (overactivity) together with the involvement of other neurotransmitter system
      imbalances as likely contributors. The clinical importance of the proposed
      mechanism is that successful management of psychotic symptoms in PD may rely on a
      multitarget approach to restore neurotransmitter imbalances rather than focusing
      exclusively on the dopaminergic dysfunction.

PMID- 15999237
TI  - Vaccination against herpes zoster, small RNA against ALS and IgG antibodies in
      stiff-person syndrome.

PMID- 15999239
TI  - Percutaneous repair of radial artery pseudoaneurysm in a hemodialysis patient
      using sonographically guided thrombin injection.
AB  - We report a case of a radial artery pseudoaneurysm complicating an incorrect
      puncture of a Brescia-Cimino hemodialysis fistula that was treated with
      percutaneous ultrasound-guided thrombin injection. The pseudoaneurysm recurred
      after the initial successful thrombin injection. With a second injection we
      obtained permanent pseudoaneurysm occlusion. Our case illustrates that this
      procedure is an effective treatment in this type of arteriovenous fistula
      complication. We compare this case with the only similar one we could find in the
      literature.

PMID- 15999240
TI  - Bleeding duodenal varices successfully treated with balloon-occluded retrograde
      transvenous obliteration (B-RTO) assisted by CT during arterial portography.
AB  - A 60-year-old woman with massive hemorrhage from duodenal varices was transferred
      to our hospital for the purpose of transcatheter intervention. Although digital
      subtraction arterial portography could not depict the entire pathway of
      collateral circulation, the efferent route of the duodenal varices was clearly
      demonstrated on subsequent CT during arterial portography. Balloon-occluded
      retrograde transvenous obliteration (B-RTO) of the varices was performed via the
      efferent vein and achieved complete thrombosis of the varices.

PMID- 15999241
TI  - Mycotic aneurysm of the celiac trunk: from early CT sign to rupture.
AB  - We present a case of the rapid development and rupture of a mycotic celiac trunk
      aneurysm. Initially on multislice computed tomography (ms-CT) there was a normal
      celiac trunk with minimal haziness of the surrounding fat. Only 2 weeks later the
      patient went into hypovolemic shock due to a ruptured celiac aneurysm. Although
      aneurysms of the visceral arteries are rare, they are of major clinical
      importance as they carry a life-threatening risk of rupture. This case
      illustrates the use of ms-CT in detecting and evaluating visceral aneurysms, in
      order to prevent emergency operation.

PMID- 15999242
TI  - Ultrasound-guided percutaneous transabdominal treatment of a type 2 endoleak.
AB  - We describe a case of multiple endoleaks following endovascular repair of an
      abdominal aortic aneurysm, treated by various methods. A new transabdominal
      embolization approach using color-flow duplex guidance is presented.

PMID- 15999244
TI  - RNA affinity for molecular L-histidine; genetic code origins.
AB  - Selection for affinity for free histidine yields a single RNA aptamer, which was
      isolated 54 times independently. This RNA is highly specific for the side chain
      and binds protonated L-histidine with 10(2)-10(3)-fold stereoselectivity and a
      dissociation constant (K(D)) of 8-54 microM in different isolates. These
      histidine-binding RNAs have a common internal loop-hairpin loop structure, based
      on a conserved RAAGUGGGKKN(0-36) AUGUN(0-2)AGKAACAG sequence. Notably, the
      repetitively isolated sequence contains two histidine anticodons, both implicated
      by conservation and chemical data in amino acid affinity. This site is probably
      the simplest structure that can meet our histidine affinity selection, which
      strengthens experimental support for a "stereochemical" origin of the genetic
      code.

PMID- 15999245
TI  - Long-term experimental evolution in Escherichia coli. XIII. Phylogenetic history
      of a balanced polymorphism.
AB  - We investigated the phylogenetic history of a balanced polymorphism that evolved
      in an experimental population of Escherichia coli. Previous work showed that two
      ecologically and morphologically distinct types, designated L (large) and S
      (small), arose by generation 6000 and coexisted for more than 12,000 generations
      thereafter. Here, we performed RFLP analyses using Insertion Sequence elements to
      resolve the phylogenetic history of L and S. Specifically, we sought to determine
      whether the derived S morph was monophyletic, indicating a long history of
      coexistence with L or, alternatively, S was repeatedly regenerated from L,
      indicating a series of periods with only transiently stable coexistence.
      Phylogenetic analysis of some 200 clones collected throughout the history of this
      population demonstrates that S is monophyletic. We then performed competition
      assays using clones of both morphs from different generations to determine
      whether either or both lineages continued to undergo genetic adaptation. Indeed,
      both lineages continued to adapt, and their continued evolution contributed to
      fluctuations in their relative abundance over evolutionary time. Based on their
      phylogenetic history and independent evolutionary trajectories, S and L fulfill
      Cohan's criteria for being different asexual species.

PMID- 15999246
TI  - The promise and peril of continuous in vitro evolution.
AB  - Experimental evolution methods can be used to address and illuminate issues
      central to the understanding of evolutionary theory. One of the most powerful of
      these methods involves the in vitro evolution of nucleic acid enzymes, taking
      advantage of the direct relationship between the genotype of a nucleic acid
      sequence and the phenotype of its associated catalytic function. This review and
      commentary focuses on the past, present, and future potential of systems for the
      continuous in vitro evolution of nucleic acid enzymes as tools for modeling
      evolutionary processes in biology. It offers a candid appraisal of both the
      strengths and the limitations of these systems.

PMID- 15999247
TI  - Down the slippery slope: plastid genome evolution in Convolvulaceae.
AB  - Cuscuta (dodder) is the only parasitic genus found in Convolvulaceae (morning
      glory family). We used long PCR approach to obtain large portions of plastid
      genome sequence from Cuscuta sandwichiana in order to determine the size,
      structure, gene content, and synteny in the plastid genome of this Cuscuta
      species belonging to the poorly investigated holoparasitic subgenus Grammica.
      These new sequences are compared with the tobacco chloroplast genome, and, where
      data are available, with corresponding regions from taxa in the other Cuscuta
      subgenera. When all known plastid genome structural rearrangements in parasitic
      and nonparasitic Convolvulaceae are considered in a molecular phylogenetic
      framework, three categories of rearrangements in Cuscuta are revealed:
      plesiomorphic, autapomorphic, and synapomorphic. Many of the changes in Cuscuta,
      previously attributed to its parasitic mode of life, are better explained either
      as plesiomorphic conditions within the family, i.e., conditions shared with the
      rest of the Convolvulaceae, or, in most cases, autapomorphies of particular
      Cuscuta taxa, not shared with the rest of the species in the genus. The
      synapomorphic rearrangements are most likely to correlate with the parasitic
      lifestyle, because they represent changes found in Cuscuta exclusively. However,
      it appears that most of the affected regions, belonging to all of these three
      categories, have probably no function (e.g., introns) or are of unknown function
      (a number of open reading frames, the function of which, if any, has yet to be
      discovered).

PMID- 15999248
TI  - Effect of the status after ear surgery and ear pathology on the results of
      infrared tympanic thermometry.
AB  - Most publications that deal with infrared tympanic thermometry (ITT) have
      performed a comparison between the established temperature measurements and ITT.
      However, to date an understanding of the influence of pathological ear findings
      on ITT test results is incomplete. Therefore, in the present study ITT was
      performed in healthy adults (n =21), adult patients with monaural central
      perforation (n =31) or strong scar formations (n =24) of the tympanic membrane
      and 18 adult patients after monaural canal wall down surgery. Right and left ear
      and oral temperature were measured three times by one investigator in a room with
      a constant temperature of 20-22 degrees C. Between every measurement there was a
      free time interval of 2 min. In healthy adults (36.50 degrees C vs. 36.51 degrees
      C) patients with monaural central perforation of the tympanic membrane (36.41
      degrees C vs. 36.34 degrees C) and with monaural strong scar formations in the
      tympanic membrane (36.39 degrees C vs. 36.45 degrees C), no significant
      difference between the right and left ear could be proved. In contrast to this, a
      significantly higher temperature in the surgically treated ear compared to the
      healthy side (36.97 degrees C vs. 36.31 degrees C; P <0.001) occurred in patients
      with a status of after monaural canal wall down surgery. In summary, it could be
      demonstrated that, in contrast to minor ear surgery, major ear surgery such as
      canal wall down has a significant influence on the results of ITT. If a patient's
      history gives reference to previous ear surgery, an otoscopic examination is
      necessary in order to exclude the presence of an after-canal-wall-down surgery
      status and thus to avoid false ITT test results.

PMID- 15999249
TI  - Giant sigmoid lipoma covered by a villous adenoma.

PMID- 15999251
TI  - Effect of training and strict guidelines on the reliability of risk adjustment
      systems in paediatric intensive care.
AB  - OBJECTIVE: Many risk-adjustment systems have significant interobserver
      variability in everyday clinical practice. This can be partly corrected by strict
      guidelines and training. These issues have not been well studied in the
      paediatric setting. We assessed the reliability of two widely used paediatric
      scoring systems, the Paediatric Risk of Mortality (PRISM) and Paediatric Index of
      Mortality (PIM), before and after a special training program. DESIGN: Prospective
      observational multi-centred cohort study. INTERVENTION: Twenty-seven physicians
      from five paediatric intensive care units (PICUs) assessed severity of illness in
      20 selected patients using PRISM and PIM scores before and after a special
      training program. Physicians were divided according to level of PICU experience:
      intensivists (>3 years experience, n=12), fellows (6-30 months experience, n=6)
      and residents (<6 months experience, n=9). Intraclass correlation was used to
      compare scoring reliability before and after training. MEASUREMENTS AND RESULTS:
      Wide variability in PRISM and PIM scoring was observed before training
      (intraclass correlation for PRISM scores 0.24-0.73, intraclass correlation for
      PIM scores 0.16-0.33). Training and implementation of guidelines led to
      significant increases in interobserver agreement (intraclass correlation 0.74
      0.86 for PRISM and 0.88-0.95 for PIM scores), although some variability remained.
      CONCLUSION: Our results show that the reliability of PRISM and PIM risk
      adjustment systems in daily clinical practice is much lower than expected.
      Training and guidelines can significantly increase interobserver agreement. These
      factors should be taken into account when using these systems for benchmarking,
      or to compare quality of care between different PICUs.

PMID- 15999252
TI  - Effect of the Y-piece of the ventilation circuit on ventilation requirements in
      extremely low birth weight infants.
AB  - OBJECTIVE: Volutrauma caused by high tidal volumes contributes considerably to
      the development of bronchopulmonary dysplasia. Yet high tidal volumes are
      required to overcome dead space. In an experimental arrangement we tested whether
      reduction of dead space might reduce ventilation requirements and thus reduce
      volutrauma in preterm infants. MATERIALS AND METHODS: The time required to
      eliminate CO2 by standardized mechanical ventilation from a preterm infant's test
      lung flooded with CO2 was measured. Four different Y-pieces and flow sensor
      combinations were tested with and without a device for closed suction: Y-piece
      without flow sensor; integrated flow sensor; small dead-space flow sensor; and a
      new dead-space free-flow sensor for preterm infants. CO2 concentrations were
      measured by a capnograph. Mean CO2 elimination times (+/-SD) were compared.
      RESULTS: Mean CO2 elimination time was 37.5 s (+/-1.18 s) with and 37.4 s (+/
      0.97 s) without closed suction device for the Y-piece without flow sensor, 47.7 s
      (+/-0.82 s) and 45.5 s (+/-1.18 s) for the integrated flow sensor, 42.5 s (+/
      1.27 s) and 41.1 s (+/-0.99 s) for the small dead-space flow sensor and 38.3 s
      (+/-1.16 s) and 36.8 s (+/-0.79 s) for the dead-space free-flow sensor.
      CONCLUSION: CO2 elimination time with and without closed suction device was
      nearly identical for the Y-piece without flow sensor and for the dead-space free
      flow sensor. With both systems, ventilation requirements were significantly lower
      than for the integrated flow sensor and for the small dead-space flow sensor
      (integrated flow sensor vs dead-space free-flow sensor 23.6 and 24.5%,
      respectively, small dead-space flow sensor vs dead-space free flow sensor 11.7
      and 10.9%, respectively); thus, we think that introduction of the innovative dead
      space free-flow sensor into clinical practice might reduce incidence and severity
      of bronchopulmonary dysplasia by reduction of volutrauma.

PMID- 15999250
TI  - [Evidence based diagnostic procedures for the determination of suspected blunt
      cervical spine injuries. Development of an algorithm].
AB  - BACKGROUND: The aim of this study was to present existing publications,
      describing various diagnostic procedures as well as considering the evidence
      supporting them, to develop a recommendation for diagnosis. MATERIAL AND METHODS:
      We reviewed relevant publications between 1966 and 2004 by a systemic literature
      search in MEDLINE, EMBASE, National Guideline Clearinghouse, Cochrane Library as
      well as a manual reference search. Keywords were cervical spine, cervical
      vertebrae, spinal, spinal cord, injury, trauma, fracture, dislocation, imaging,
      radiography, flexion, extension, fluoroscopy, computed tomography, computed
      scanning, and magnetic resonance imaging. The selected search results were then
      classified into levels of evidence. RESULTS: From among a total of 10,000
      publications, 137 relevant publications were stringently reviewed. The level of
      evidence is on the whole limited due to deficit data; therefore, only class II
      III recommendations are possible. We developed an algorithm for the diagnostic
      approach to suspected trauma of the cervical spine. This clinical algorithm
      displays the complex diagnosis of cervical spine injury in a clear and logically
      structured process. CONCLUSIONS: The diagnostic algorithm for cervical spine
      injury meets the presently required standards and maximizes care for the newly
      injured. The development, which can be followed using evidence-based medicine, is
      transparent and therefore aids the decision process when choosing an adequate
      diagnostic procedure.

PMID- 15999253
TI  - Nosocomial viral ventilator-associated pneumonia in the intensive care unit: a
      prospective cohort study.
AB  - OBJECTIVE: To determine the incidence, risk factors, and clinical relevance of
      viral ventilator-associated pneumonia (VAP) in an adult intensive care unit
      (ICU). DESIGN: Prospective observational study. SETTING: A 22-bed adult medical
      ICU in a university hospital. PATIENTS: All consecutive adult patients ventilated
      more than 48 h in a 9-month period including regular seasonal viral infections.
      INTERVENTIONS: A tracheobronchial aspirate upon enrollment and at the time of VAP
      suspicion. MEASUREMENTS AND RESULTS: All respiratory specimens were tested in
      culture, indirect immunofluorescence assay, and PCR or RT-PCR for virological
      assessment. Patients were followed until ICU discharge or death. One hundred
      thirty-nine patients were included. Upon enrollment, a respiratory virus was
      detected in the tracheobronchial aspirate in 25% of patients (35 of 139). The
      incidence of VAP, defined according to clinical daily evaluation, was 28% (39 of
      139 patients). A bacteria was documented in 74% of cases, whereas no case of a
      causative viral infection was encountered among VAP patients; however, herpes
      simplex virus type-1 (HSV 1) infection was detected in respiratory specimens of
      31% of VAP (12 of 39). CONCLUSIONS: We found a high incidence of HSV-1 infection
      in VAP patients; however, nosocomial viral VAP is likely to be rare in ICU, as
      assessed by the absence of respiratory virus-induced VAP identified in this
      prospective cohort study.

PMID- 15999254
TI  - Temporal changes in whole-blood and plasma glutathione in ICU patients with
      multiple organ failure.
AB  - OBJECTIVE: This study investigated the temporal changes in whole-blood and plasma
      glutathione in ICU patients with multiple organ failure. DESIGN AND SETTING:
      Prospective and descriptive pilot study performed in an ICU with eight beds at a
      university hospital. PATIENTS: Critically ill patients (n=11) with multiple organ
      failure and ICU stay of at least 6 days were consecutively included. Patients
      with chronic obstructive pulmonary disease (n=21) and healthy volunteers (n=10)
      were used as reference groups. MEASUREMENTS AND RESULTS: Whole-blood and plasma
      glutathione were measured every 72 h. Total glutathione and the reduced fraction
      were determined in whole blood. The oxidized fraction and the redox status were
      calculated from these values. In plasma only the total concentration was
      determined. Patients were studied for 6-15 days. Nutrition was supplied according
      to routines supplying basal needs including glutamine. Both total and reduced
      glutathione was found to be depleted in whole blood compared to the reference
      groups. Redox status indicated continuing oxidative stress. Plasma glutathione
      showed higher values in total concentrations than the reference groups.
      CONCLUSIONS: This study demonstrates that glutathione remains depleted in whole
      blood. This contrasts to what has previously been shown in skeletal muscle where
      a restitution of glutathione concentration is seen.

PMID- 15999255
TI  - Changes in acid-base balance following bolus infusion of 20% albumin solution in
      humans.
AB  - OBJECTIVE: To evaluate changes in acid-base balance following bolus infusions of
      a 20% albumin solution. DESIGN AND SETTING: Randomized prospective study in a
      university hospital. PATIENTS AND PARTICIPANTS: Two groups of eight patients each
      undergoing gynecological surgery. INTERVENTIONS: Patients were randomly assigned
      to receive either 0.9% saline or lactated Ringer's solution. At the end of
      surgery two boluses of 0.5 g/kg body weight of a 20% albumin solution were
      administered. Arterial blood gases, electrolytes, and total protein were
      measured. The strong ion difference and the amount of weak plasma acid were
      calculated. pH and titratable acidity of the 20% albumin solution were
      determined. MEASUREMENTS AND RESULTS: The infusion of a 20% albumin solution
      resulted in a significant decrease in pH from 7.284 to 7.262 in the saline group
      and from 7.422 to 7.394 in the Ringer's group. In both groups the 20% albumin
      solution caused an increase in strong ion difference and an increase in the
      amount of weak plasma acid. The observed changes in serum bicarbonate
      concentration were in good agreement with the changes in strong ion difference
      and the amount of weak plasma acid. The 20% albumin solution possessed a pH of
      6.95 and a titratable acidity of 8.5 [corrected] mEq/l. CONCLUSIONS: According to
      the Stewart approach, the observed changes in acid-base balance are the net
      result of the two opposing effects of the strong ion difference and the amount of
      weak plasma acid. Alternatively, the acidifying effect of the 20% albumin
      solution may stem from the titratable acid content of the solution.

PMID- 15999256
TI  - Prone positioning: do not turn it off!

PMID- 15999257
TI  - Short-term effects of prone position in chronic obstructive pulmonary disease
      patients with severe acute hypoxemic and hypercapnic respiratory failure.
AB  - OBJECTIVE: To assess the short-term effects of prone positioning (PP) in chronic
      obstructive pulmonary disease (COPD) patients with severe hypoxemic and
      hypercapnic respiratory failure requiring invasive mechanical ventilation. DESIGN
      AND SETTING: Prospective observational study in the general intensive care unit
      of a university-affiliated hospital. PATIENTS: 11 consecutive COPD patients with
      persistent hypoxemia (PaO2/FIO2 < or = 200 mmHg with FIO2 > or = 0.6) and
      hypercapnia requiring invasive mechanical ventilation. Patients with adult
      respiratory distress syndrome or left ventricular failure were excluded. Mean age
      was 73+/-11 years, mean weight 86+/-31 kg, mean SAPS II 53+/-10, and ICU
      mortality 36%. INTERVENTIONS: Patients were turned every 6 h. MEASUREMENTS AND
      RESULTS: A response to PP (20% or greater PaO2/FIO2 increase) was noted in 9
      (83%) patients. Blood gases were measured in the PP and supine (SP) positions 3 h
      after each turn, for 36 h, yielding six measurement sets (SP1, PP1, SP2, PP2,
      SP3, and PP3). PaO2/FIO2 was significantly better in PP: 190+/-26 vs. 113+/-9
      mmHg for PP1/SP1, 175+/-22 vs. 135+/-16 mmHg for PP2/SP2, and 199+/-24 vs. 151+/
      13 mmHg for PP3/SP3. After PP1 PaO2/FIO2 remained significantly improved, and the
      PaO2/FIO2 improvement from SP1 to SP2 was linearly related to PaO2/FIO2 during
      PP1 (r=0.8). The tracheal aspirate volume improved significantly from SP1 to PP1.
      PaCO2 was not significantly affected by position. CONCLUSIONS: PP was effective
      in treating severe hypoxemia in COPD patients. The first turn in PP was
      associated with increased tracheal aspirate.

PMID- 15999259
TI  - Devastating endophthalmitis following penetrating ocular injury during night
      sleep from orthodontic headgear: case report and literature review.
AB  - BACKGROUND: Complications associated with the use of extra-oral traction devices
      (orthodontic headgear or facebow) including facial and ocular injuries, are
      considered infrequent. METHODS: We describe the case of a 12-year-old boy who was
      inadvertently injured by the metallic bow of orthodontic headgear during sleep
      and developed blinding intra-ocular infection (endophthalmitis). RESULTS: The
      injury resulted in corneal perforation. Visual acuity at presentation was 20/60
      but deteriorated rapidly to light perception despite prompt medical and surgical
      treatment for endophathalmitis. Sympathetic ophthalmia developed and was
      controlled with systemic corticosteroids and imuran. Bacterial cultures showed
      mixed infection by gram-negative bacilli and Streptococcus viridans. In 10 (91%)
      out of the 11 eyes that were reported including our case, the visual acuity was
      hand movement perception or less. CONCLUSIONS: The increase in case reports of
      such injuries should prompt the establishment of a standard policy regarding the
      use of orthodontic headgear and increase awareness of orthodontists and
      ophthalmologists to the blinding potential of even trivial and minor ocular
      injuries by orthodontic headgear. Intervention should be one step ahead compared
      with ocular injuries from other foreign bodies.

PMID- 15999258
TI  - Anodal transcranial direct current stimulation of prefrontal cortex enhances
      working memory.
AB  - Previous studies have claimed that weak transcranial direct current stimulation
      (tDCS) induces persisting excitability changes in the human motor cortex that can
      be more pronounced than cortical modulation induced by transcranial magnetic
      stimulation, but there are no studies that have evaluated the effects of tDCS on
      working memory. Our aim was to determine whether anodal transcranial direct
      current stimulation, which enhances brain cortical excitability and activity,
      would modify performance in a sequential-letter working memory task when
      administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects
      underwent a three-back working memory task based on letters. This task was
      performed during sham and anodal stimulation applied over the left DLPFC.
      Moreover seven of these subjects performed the same task, but with inverse
      polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the
      primary motor cortex (M1). Our results indicate that only anodal stimulation of
      the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal
      stimulation of M1, increases the accuracy of the task performance when compared
      to sham stimulation of the same area. This accuracy enhancement during active
      stimulation cannot be accounted for by slowed responses, as response times were
      not changed by stimulation. Our results indicate that left prefrontal anodal
      stimulation leads to an enhancement of working memory performance. Furthermore,
      this effect depends on the stimulation polarity and is specific to the site of
      stimulation. This result may be helpful to develop future interventions aiming at
      clinical benefits.

PMID- 15999260
TI  - Hybrid bounded error observers for uncertain bioreactor models.
AB  - In this paper, we build bounded error observers for a common class of partially
      known bioreactor models. The main idea is to construct hybrid bounded observers
      "between" high gain observer, which has an adjustable convergence rate but
      requires perfect knowledge of the model, and asymptotic observer which is very
      robust towards uncertainty but has a fixed convergence rate. An hybrid bounded
      error observer which reconstructs the two state variables is constructed
      considering two steps: first step is similar to a high gain observer meaning that
      fast convergence rate but error depending on the knowledge of the model are
      obtained; second step is a switch to an observer similar to the asymptotic one
      meaning that fixed convergence rate towards an error as small as desired is
      obtained. Thus, a better convergence rate of estimated variables than the
      classical asymptotic observer is obtained.

PMID- 15999261
TI  - CAM for cancer?

PMID- 15999262
TI  - Long-term use of peripherally inserted central venous catheters for cancer
      chemotherapy in children.
AB  - BACKGROUND: Peripherally inserted central venous catheters (PICCs) have been
      increasingly used in pediatric patients. However, little is known about the
      incidence and risk of complications when using this device in children with
      cancer. The purposes of this study are to assess the feasibility of PICCs and to
      determine the risk factors for PICC-related complications in pediatric patients
      with various types of malignancies. PATIENTS AND METHODS: We attempted to place
      PICCs in 53 patients with a median age of 5 years ranging from 2 months to 20
      years. PICCs were used to administer fluid, parenteral nutrition, anticancer
      agents, antibiotics, and blood products and also for the through-line blood
      sampling. The duration of catheterization and the incidence of PICC-related
      complications requiring removal were retrospectively evaluated in association
      with the diagnosis, sex, age and body weight of the patients, size, insertion
      site and tip location of the catheters, type of treatment, and duration of
      leukopenia. RESULTS: PICCs were successfully placed in 109 of 112 attempts
      (97.3%) in 53 patients, and they were followed for a total of 11,797 catheter
      days (median placement, 87 days; range, 3 to 512 days). Fifty five PICCs (50.5%)
      were removed as a result of PICC-related complications with a rate of 4.66 per
      1,000 catheter days. The most common reasons for catheter removal were occlusion
      (n=18), breakage/leakage (15), and infection (10). More than 70% of such
      complications occurred more than 30 days after placement. The catheter tip
      location in the superior vena cava or the right atrium might decrease the risk of
      complications. Other parameters did not influence the incidence of complications.
      CONCLUSIONS: PICCs were found to provide a reliable access for prolonged
      intravenous administration and blood sampling in children intensively treated for
      hematologic and solid malignancies, thus leading to a reduction of physical pain
      and psychological stress in such patients. However, the long-term placement of
      PICCs may also be related to an increased risk of complications.

PMID- 15999263
TI  - Look before leaping: combined opioids may not be the rave.
AB  - The use of combinations of potent opioids is a common clinical practice. The
      addition of one potent opioid to another has been recommended to reduce opioid
      side effects, improve pain control, and limit dose escalation of the first
      opioid. The advantages of using combined opioids have been reported to be
      relative to differences in receptor activation versus endocytosis (RAVE).
      However, the advantages and detriment to combining opioids are related to
      naturally occurring opioid receptor dimers. Dimers and oligomers result in a
      unique opioid pharmacodynamics which influence opioid binding, G protein
      interactions, desensitization, receptor trafficking, and endocytosis. The
      pharmacodynamics of dimers may lead to positive or negative cooperativity when
      two opioids are combined. The use of multiple opioids in practice can lead to
      increased risk for dosing errors, reduced patient compliance, increased drug
      interactions and cost. Opioid combinations should not be used until prospective
      randomized trials clarify the benefits and safety.

PMID- 15999265
TI  - [Infection control measures in intensive care units. Results of the German
      Nosocomial Infection Surveillance System (KISS)].
AB  - BACKGROUND: Aim of this study was to determine to what extent evidence-based
      infection control recommendations are applied in German intensive care units
      (ICUs). METHODS: A questionnaire concerning handling of tubes, central vascular
      catheters (CVC), urinary tract catheters and methicillin-resistant Staphylococcus
      aureus (MRSA) positive patients was sent to 230 participants of the German
      Nosocomial Infection Surveillance System (KISS). RESULTS: Nasal intubation is
      routinely performed in 9% of ICUs, all recommended measures for CVC insertion
      were obeyed by 43% of ICUs and one-third of ICUs conduct regular screening of
      urine in catheterized patients. Urinary tract catheters are replaced at defined
      time intervals in 37% of ICUs. MRSA positive patients are not isolated in 5% of
      ICUs. MRSA screening on admission is not performed for high risk patients in 16%
      of ICUs. CONCLUSIONS: There are still many German ICUs in which evidence-based
      recommendations are not implemented. Training of staff is necessary to improve
      quality of patient care.

PMID- 15999264
TI  - Measuring quality of life in patients with pleural mesothelioma using a modified
      version of the Lung Cancer Symptom Scale (LCSS): psychometric properties of the
      LCSS-Meso.
AB  - Health-related quality of life (QOL) assessment is a key component in patient
      assessment and the development of therapies for malignant pleural mesothelioma.
      However, no mesothelioma-specific instrument was available. The Lung Cancer
      Symptom Scale (LCSS), a site-specific instrument used to assess QOL in patients
      with lung cancer, was identified as an instrument that could be appropriate. A
      modified nine-item patient-reported and six-item observer-reported LCSS was
      incorporated into two clinical trials of pemetrexed in patients with pleural
      mesothelioma. Basic psychometric properties of feasibility, reliability, and
      validity were tested. Properties were stable or enhanced by deletion of the
      hemoptysis item. Feasibility was demonstrated with a high completion rate of 90%
      by 512 patients. Reliability was acceptable, with good internal consistency for
      the eight-item measure (alpha coefficient=0.86) and reasonably good for the five
      item observer measure (alpha coefficient=0.66); there was also good stability for
      the patient measure using test-retest (r=0.87). Content validity was supported by
      a literature review and patient self-report of presenting symptoms (>90% of
      patients had three or more symptoms). Construct validity was well supported by
      finding better scores in the higher performance status groups and greater symptom
      improvement in patients with tumor response, good concordance with the LCSS
      conceptual model and good explanation of variance for summation items, and a high
      degree of convergence between the patient and observer forms (r=0.57). Criterion
      related validity was supported by predicting survival time, time to progression,
      and tumor response rate; all three summary items and the total LCSS-Meso score
      were statistically significant predictors (p<0.005). The LCSS-Meso is a feasible,
      reliable, and valid instrument to assess health-related QOL in patients with
      pleural mesothelioma. One item, hemoptysis, was dropped from the original LCSS
      based on these findings.

PMID- 15999266
TI  - [Awareness under remifentanil-propofol anaesthesia].
AB  - We report on a 49-year-old female patient suffering from recurrent carcinoma of
      the rectum, who underwent a palliative Hartmann operation for an anus praeter
      reconstruction. After a remifentanil bolus of 90 microg and a propofol bolus of
      200 mg, anaesthesia was maintained with 0.25 microg/kg/min remifentanil and 4
      mg/kg propofol, and after skin incision with 1.0 microg/kg/min remifentanil and 5
      mg/kg/h propofol. Throughout the operation, the patient showed a stable blood
      pressure of 120-130/80 mmHg but 15 min after skin incision the heart rate
      suddenly rose to 140 beats/min, so remifentanil was increased to 1.8
      microg/kg/min and propofol to 8 mg/kg/h. Over a time period of 15 min the heart
      rate decreased to 90 beats/min. Subsequently vegetative parameters stayed within
      the normal range (heart rate 90 beats/min, blood pressure 120-130/80 mmHg) so
      that continuous administration of remifentanil and propofol could be tapered.
      After completion of skin sutures, administration of remifentanil and propofol was
      terminated. After extubation the patient reported having heard conversations
      contributable to the end of the operation and the sentence: "now we're done" was
      clearly remembered. The patient stated that she had not been able to move any
      part of her body, that she had perceived the situation as extremely unpleasant
      and dangerous and that she had felt severe pain. At the postoperative rounds the
      patient refused any psychological and psychiatric help.

PMID- 15999267
TI  - [Diagnosis and treatment of breast cancer].
AB  - Today, the treatment of breast cancer should be carried out in interdisciplinary
      centers. Preoperative diagnosis comprises clinical examination, mammography,
      ultrasound, and possibly magnetic resonance imaging. To exclude metastases, X-ray
      of the thorax, ultrasound examination of the abdomen (liver), and skeletal
      scintigraphy have to be performed. Preoperatively, the possibility of primary
      systemic therapy to reduce the size of the tumor can be investigated in order to
      increase the likelihood of surgery preserving the breast, the goal in at least
      70% of cases and which always requires radiation therapy. Histopathological
      investigation to confirm the R0 resection must always be carried out. In the case
      of intraductal components, the tumor-free periphery must be larger. Systemic
      therapy is based on risk groups and comprises hormonal therapy, chemotherapy, and
      immune (antibody) therapy. Follow-up should focus in particular on determining
      whether relapse has occurred or contralateral breast carcinoma has developed.

PMID- 15999268
TI  - Determination of platinum-group metals and lead in vegetable environmental bio
      monitors by voltammetric and spectroscopic techniques: critical comparison.
AB  - This paper reports voltammetric sequential determination of Pt(II), Pd(II), and
      Rh(III), by square-wave adsorption stripping voltammetry (SWAdSV), and Pb(II), by
      square-wave anodic stripping voltammetry (SWASV), in vegetable environmental
      matrices. Analytical procedures were verified by the analysis of the standard
      reference materials: Olive Leaves BCR-CRM 062 and Tomato Leaves NIST-SRM 1573a.
      Precision and accuracy, expressed as relative standard deviation and relative
      error, respectively, were always less than 6% and the limits of detection (LOD)
      for each element were below 0.096 mug g(-1). Once set up on the standard
      reference materials, the analytical procedure was transferred and applied to
      laurel leaves sampled in proximity to a superhighway and in the Po river mouth
      area. A critical comparison with spectroscopic measurements is discussed.

PMID- 15999269
TI  - Direct determination of total sulfur in wine using a continuum-source atomic
      absorption spectrometer and an air-acetylene flame.
AB  - Determination of sulfur in wine is an important analytical task, particularly
      with regard to food safety legislation, wine trade, and oenology. Hitherto
      existing methods for sulfur determination all have specific drawbacks, for
      example high cost and time consumption, poor precision or selectivity, or matrix
      effects. In this paper a new method, with low running costs, is introduced for
      direct, reliable, rapid, and accurate determination of the total sulfur content
      of wine samples. The method is based on measurement of the molecular absorption
      of carbon monosulfide (CS) in an ordinary air-acetylene flame by using a high
      resolution continuum-source atomic-absorption spectrometer including a novel high
      intensity short-arc xenon lamp. First results for total sulfur concentrations in
      different wine samples were compared with data from comparative ICP-MS
      measurements. Very good agreement within a few percent was obtained.

PMID- 15999270
TI  - Determination of jasmonic acid in bark extracts from Hevea brasiliensis by
      capillary electrophoresis with laser-induced fluorescence detection.
AB  - A simple and sensitive method is described for determination of jasmonic acid
      (JA) in plant tissues. The method is based on derivatization of JA with 5
      bromomethylfluorescein (5-BMF) and separation and quantification of the resulting
      5-BMF-JA derivative by capillary electrophoresis coupled to laser-induced
      fluorescence detection (CE-LIF). The derivatization conditions were studied in
      detail. Our results indicated that 5-BMF-labeled JA could be well separated from
      other plant hormones present in the sample by use of 20 mmol L(-1) borate buffer
      (pH 8.5). The response to JA was a linear function of concentration in the range
      1 to 100 micromol L(-1), with a correlation of 0.9986. Our preliminary work
      showed that the proposed method had fairly good selectivity and sensitivity. Only
      small amounts of plant sample are needed to complete the analysis. This described
      method enables the analysis of JA in crude extracts without extra purification
      and enrichment procedures.

PMID- 15999271
TI  - Performance of a new nebulizer system for simultaneous determination of Sb, Sn
      (hydride generation), V, and Zn by ICP-OES.
AB  - A new nebulizer system is described that extends the analytical capability of the
      inductively coupled plasma technique to include the simultaneous determination of
      two elements Sb and Sn (hydride-forming), with two conventional elements, V and
      Zn. The main advantage of this system is its simultaneous determination of
      elements that form volatile hydrides and elements that do not, without any
      instrumental changes. Optimization of reaction and instrumental conditions was
      performed to characterize the new system. The performance of the new nebulizer
      system was evaluated by studying the effect of some transition metals (Ni, Cu,
      Co, and Fe, 1-1000 mg L(-1)) on the Sb, Sn, V, and Zn emission signals (1 mg L(
      1)). Interferences from transition metal ions were found to be insignificant for
      determination of the four elements in presence of L: -cysteine. Long-term and
      short-term stability was also evaluated. The precision, expressed as RSD for 15
      replicate measurements was 0.7% for Sb, 1.7% for Sn, 2.5% for V, and 2.3% for Zn
      at 200 microg L(-1) of each analyte. The detection limits obtained were 0.52,
      1.3, 3.2, and 4.7 microg L(-1) for Sb, Sn, V, and Zn, respectively. Spike and
      recovery experiments were performed on the NIST 1643c trace metals in water
      standard reference material and results were in agreement with the certified
      values.

PMID- 15999272
TI  - A phase I trial of celecoxib in combination with docetaxel and irinotecan in
      patients with advanced cancer.
AB  - PURPOSE: This phase I study was conducted to determine the safety, tolerability
      and maximum tolerated dose of the combination of celecoxib, a selective
      cyclooxygenase-2 inhibitor, with docetaxel and irinotecan, in patients with
      advanced solid tumors. PATIENTS AND METHODS: Patients with solid tumors received
      one of three escalating dose levels of daily celecoxib in combination with
      docetaxel and irinotecan administered on days 1 and 8 of an every 21-day cycle.
      Toxicities were graded by the National Cancer Institute Common Toxicity Criteria
      (NCI CTC) and recorded as maximum grade per patient for each treatment cycle.
      RESULTS: A total of 19 patients received 90 cycles of treatment through three
      dose levels. Dose-limiting toxicities were nausea and diarrhea. The most common
      treatment-related toxicities in all cycles of treatment were alopecia, fatigue,
      diarrhea, nausea, vomiting, anemia, anorexia, and edema.. The maximum tolerated
      dose was established at celecoxib 400 mg twice a day continuously, weekly
      docetaxel 30 mg/m2 and irinotecan 50 mg/m2 for 2 weeks every 21 days. Disease
      stabilization (five or more cycles) was documented in eight patients. CONCLUSION:
      The combination of celecoxib with docetaxel and irinotecan did not ameliorate
      irinotecan-induced diarrhea. Although prolonged disease stabilization was
      achieved in some patients, we do not recommend combining celecoxib with docetaxel
      and irinotecan because of lack of activity and the side effect profile of this
      combination.

PMID- 15999273
TI  - Anti-TNF-alpha antibody Infliximab and glucocorticoids reduce serum vascular
      endothelial growth factor levels in patients with rheumatoid arthritis: a pilot
      study.
AB  - To compare the effect of oral glucocorticoid (GC) therapy with the effect of
      intravenous anti-TNF-alpha-therapy on serum VEGF levels of patients with
      rheumatoid arthritis (RA). Five RA patients (5/8) who had no prior treatment with
      DMARDs (Disease modifying antirheumatic drugs) or GCs were administered 20 mg
      prednisolone daily. Three patients who failed more than one DMARD therapy
      received infusion with Infliximab (200 mg). VEGF-serum levels were measured by
      enzyme-linked immunosorbent assay before treatment,and at day 10 or 13 during
      prednisolone therapy, or 14 days after the first Infliximab infusion. Serum VEGF
      levels in therapy naive RA patients (GC group) were higher than those in
      pretreated patients who received Infliximab (median serum VEGF level: 1106 vs 320
      pg/ml; P=0.1). Treatment with Infliximab as well as GCs significantly decreased
      serum VEGF levels after 10-14 days in RA patients (median serum VEGF level after
      treatment: GC group 559 pg/ml, Infliximab group 92 pg/ml; P=0.01 vs without
      treatment or preinfusion). CONCLUSIONS: Anti-TNF-alpha antibody Infliximab as
      well as GC are able to decrease serum VEGF levels in patients with active RA.
      Whether therapeutic reduction of serum VEGF levels is associated with inhibition
      of angiogenesis should be evaluated in future by imaging of synovial vasculature.

PMID- 15999275
TI  - [Therapeutic strategies for hereditary retinal diseases].

PMID- 15999274
TI  - Acute pachymeningitis mimicking subdural hematoma in a patient with polyarteritis
      nodosa.
AB  - Pachymeningitis is a very rare neurologic manifestation of polyarteritis nodosa
      (PAN). This report describes a case of acute pachymeningitis that was, initially,
      misdiagnosed as subdural hematoma on the brain CT of a patient with PAN. A 45
      year-old man, who had been diagnosed as having PAN 6 months previously, came back
      to the emergency room with complaints of sudden headache, nausea, vomiting, and
      diplopia for 3 days before his hospital admission. Initially, the noncontrast
      enhanced brain CT findings showed high densities in the bilateral tentorial and
      posterior parafalcial area, which suggested a small amount of subdural hematoma.
      However, the subsequent MRI findings revealed pachymeningitis of the bilateral
      tentoria and falx. He was treated with high-dose steroid and cyclophosphamide
      pulse therapy. Thereafter, his symptoms gradually resolved.

PMID- 15999276
TI  - Periprosthetic fractures of the femur associated with hip arthroplasty.
AB  - The nature of the treatment of periprosthetic fractures depends on the
      localisation, the stability of the prosthesis and the condition of the bone. The
      Vancouver fracture classification has proved to be of value in determining
      specific modes of treatment. The current review analyses the different
      therapeutic options resulting in a concept of fracture-specific treatment. In
      this report we propose an extended version of this classification in which
      periprosthetic fractures associated with endoprostheses anchored in the epiphysis
      or metaphysis, as well as interprosthetic fractures, are taken into
      consideration.

PMID- 15999277
TI  - Mapping the health and environmental situation in informal zones in Aleppo,
      Syria: report from the Aleppo household survey.
AB  - OBJECTIVES: Despite large communities living in informal zones around major
      cities in Syria, there is currently no information on the health and
      environmental situations in these areas. From May to August 2004, the Syrian
      Center for Tobacco Studies (SCTS) conducted the first household survey aiming to
      provide a baseline map of main health problems and exposures affecting these
      communities in Aleppo, the second largest city in Syria (2,500,000 inhabitants).
      METHODS: Information on 1,021 participants randomly selected using stratified
      cluster sampling were available (46% males, mean age 34+/-11.7, age range 18-65
      years, response rate 86%), including self-reported health/disability, exposures,
      and saliva cotinine measurement. RESULTS: Some positive findings include better
      than expected access to electricity, piped water, city sewage, and the use of
      propane for cooking. Particular areas of concern include high fertility rates,
      overcrowded housing conditions, and gender inequality in education and work.
      Household features likely to reflect negatively on residents' health include the
      use of diesel chimneys for heating and lack of smoking restrictions. Overall,
      residents of informal zones suffer from substantial physical and mental health
      problems and are exposed to high levels of indoor air pollution. All seem to
      affect women and the elderly disproportionately, while men are more affected by
      smoking, occupational respiratory exposures, and injuries. Both infectious and
      non-infectious respiratory outcomes were very common among study participants.
      Chronic and degenerative disease, including CVD and joint problems, were a source
      of substantial morbidity among the studied communities. CONCLUSIONS: This study
      highlights major health and environmental specificities of marginalized
      populations living in Aleppo, where women seem to bear a disproportionate burden
      of poor health and disability. Smoking and exposure to tobacco smoke seem among
      the major exposures facing these populations.

PMID- 15999278
TI  - PCR-RFLP analysis: a promising technique for host species identification of blood
      meals from tsetse flies (Diptera: Glossinidae).
AB  - A polymerase chain reaction with the restriction fragment length polymorphism
      (PCR-RFLP) method using universal primers complementary to the conserved region
      of the cytochrome b gene (cyt b) of the mitochondrion DNA (mtDNA) of vertebrates
      was applied to the identification of the origin of blood meals in tsetse flies.
      Blood samples from ten potential tsetse hosts of the family bovidae (cattle,
      water buffalo, red buffalo, waterbuck, springbok, goat, sheep, sable antelope,
      oryx and dik-dik) were included in this study. Sites for appropriate restriction
      endonucleases cuts were chosen by pairwise alignment of the amplified 359 bp
      fragments. A flow chart of endonucleases digestion using three restriction
      enzymes (e.g. TaqI, AluI and HindII) for the unequivocal identification of the
      respective bovid species was developed. A number of additional non-specific DNA
      fragments attributed to the co-amplification of cytochrome b pseudogenes were
      observed in some species (e.g. in red buffalo and dik-dik after digestion with
      AluI) but did not hamper assignment of bovid species. The detection rate of host
      DNA in tsetse by PCR-RFLP was 100, 80, 60 and 40% at 24, 48, 72 and 96 h after in
      vitro feeding, respectively. Identification of the last blood meal was possible
      even when tsetse had previously fed on different hosts.

PMID- 15999279
TI  - Seasonal variation of Hepatozoon spp. (Apicomplexa, Hepatozoidae) parasitemia
      from Boa constrictor amarali (Serpentes, Boidae) and Hydrodynastes gigas
      (Serpentes, Colubridae).
AB  - The aim of this study was to evaluate the parasitemia variation of three
      Hepatozoon species in Brazilian snakes. This study was conducted between 2001 and
      2003 and included Hepatozoon terzii from Boa constrictor amarali, and Hepatozoon
      migonei and Hepatozoon cyclagrasi from Hydrodynastes gigas. It was observed that
      the parasitemia tended to decrease in all three Hepatozoon species but the
      parasites were not eliminated. This data suggest that Hepatozoon infection may be
      similar to Toxoplasma gondii infection, in that it persists throughout host life.

PMID- 15999280
TI  - Adhesive capsulitis: sonographic changes in the rotator cuff interval with
      arthroscopic correlation.
AB  - OBJECTIVE: To evaluate the sonographic findings of the rotator interval in
      patients with clinical evidence of adhesive capsulitis immediately prior to
      arthroscopy. DESIGN AND PATIENTS: We prospectively compared 30 patients with
      clinically diagnosed adhesive capsulitis (20 females, 10 males, mean age 50
      years) with a control population of 10 normal volunteers and 100 patients with a
      clinical suspicion of rotator cuff tears. Grey-scale and colour Doppler
      sonography of the rotator interval were used. RESULTS: Twenty-six patients (87%)
      demonstrated hypoechoic echotexture and increased vascularity within the rotator
      interval, all of whom had had symptoms for less than 1 year. Three patients had
      hypoechoic echotexture but no increase in vascularity, and one patient had a
      normal sonographic appearance. All patients were shown to have fibrovascular
      inflammatory soft-tissue changes in the rotator interval at arthroscopy
      commensurate with adhesive capsulitis. None of the volunteers or the patients
      with a clinical diagnosis of rotator cuff tear showed such changes. CONCLUSIONS:
      Sonography can provide an early accurate diagnosis of adhesive capsulitis by
      assessing the rotator interval for hypoechoic vascular soft tissue.

PMID- 15999281
TI  - Ultrasound of tendon tears. Part 1: general considerations and upper extremity.
AB  - The role of ultrasound (US) in assessing musculoskeletal disorders is
      persistently increasing because of its low cost, readiness, noninvasiveness, and
      possibility of allowing a dynamic examination. Secondary to increased sport
      practice, tendon tears are more frequently observed in daily medical practice.
      They deserve early diagnosis to allow proper treatment that can limit functional
      impairment. The aim of this review article is twofold: to illustrate the US
      appearance of normal tendons and to describe the US findings of the most common
      tendon tears.

PMID- 15999282
TI  - Quantitative ultrasound of the hand phalanges in a cohort of monozygotic twins:
      influence of genetic and environmental factors.
AB  - OBJECTIVE: Our objective was to evaluate the similarities and differences in bone
      mass and structure between pairs of monozygotic twins as measured by means of the
      quantitative ultrasound (QUS) technique. DESIGN: A cohort of monozygotic twins
      was measured by QUS of the hand phalanges using the DBM sonic bone profiler
      (IGEA, Carpi, Italy). The parameters studied were amplitude-dependent speed of
      sound (AD-SoS), ultrasound bone profile index (UBPI), signal dynamics (SDy) and
      bone transmission time (BTT). Linear correlation coefficients, multivariate
      linear analysis and the ANOVA test were used to assess intrapair associations
      between variables and to determine which factors influence the intrapair
      differences in QUS variables. PATIENTS: One hundred and six pairs of monozygotic
      twins were enrolled in the study, 68 females and 38 males in the age range 5 to
      71 years. RESULTS: Significant intrapair correlations were obtained in the whole
      population and separately for males and females, regarding height ( r =0.98-0.99,
      p <0.0001), weight ( r =0.95-0.96, p <0.0001), AD-SoS ( r =0.90-0.92, p <0.0001),
      BTT ( r =0.94-0.95, p <0.0001) and other QUS parameters ( r >0.74, p <0.0001).
      Multivariate analysis revealed that intrapair differences between AD-SoS, SDy,
      UBPI and BTT are significantly influenced by age in the whole population and in
      the female population. Furthermore, the ANOVA test showed, for the female group,
      a significant increase in the intrapair differences in SDy and UBPI above 40
      years. CONCLUSIONS: A relative contribution of genetic factors to skeletal status
      could be observed by phalangeal QUS measurement in monozygotic twins. A
      significant increase in the intrapair difference in QUS parameters with
      increasing age and onset of menopause also suggests the importance of
      environmental factors in the female twin population.

PMID- 15999283
TI  - Hyperphosphatemia and tumor lysis syndrome.

PMID- 15999284
TI  - The prevalence of neck pain in the world population: a systematic critical review
      of the literature.
AB  - The objective of this study was to determine the prevalence of neck pain (NP) in
      the world population and to identify areas of methodological variation between
      studies. A systematic search was conducted in five databases (MEDLINE, EMBASE,
      CINAHL, OSH-ROM, and PsycINFO), followed by a screening of reference lists of
      relevant papers. Included papers were extracted for information and each paper
      was given a quality score. Mean prevalence estimates were calculated for six
      prevalence periods (point, week, month, 6 months, year, and lifetime), and
      considered separately for age, gender, quality score, response rate, sample size,
      anatomical definition, geography, and publication year. Fifty-six papers were
      included. The six most commonly reported types of prevalence were point, week,
      month, 6 months, year, and lifetime. Except for lifetime prevalence, women
      reported more NP than men. For 1-year prevalence, Scandinavian countries reported
      more NP than the rest of Europe and Asia. Prevalence estimates were not affected
      by age, quality score, sample size, response rate, and different anatomical
      definitions of NP. NP is a common symptom in the population. As expected, the
      prevalence increases with longer prevalence periods and generally women have more
      NP than men. At least for 1-year prevalence Scandinavian countries report higher
      mean estimates than the rest of Europe and Asia. The quality of studies varies
      greatly but is not correlated with the prevalence estimates. Design varies
      considerably and standardisation is needed in future studies.

PMID- 15999285
TI  - Pediatric giant cell glioblastoma: a case report and review of the literature.
AB  - INTRODUCTION: Giant cell glioblastoma is a subtype of glioblastoma multiforme
      (GM) whose most characteristic histology is the presence of plentiful
      multinucleated giant cells. These tumours are very rare and account for only 5%
      of GM. They do not have specific localization, although normally they are
      supratentorial and affect mostly the temporal lobe. They may occur at any age,
      but mostly they occur in younger people than GM. They are infrequent in
      childhood, but they have longer survival in paediatric age. CASE REPORT: We
      present an 11-year-old girl that was operated but whose tumour recurred in a
      month after apparent total removal. DISCUSSION: We review in the literature the
      clinical, histological, immuno-histochemical and genetic characteristics, as well
      the prognosis of this tumour.

PMID- 15999286
TI  - Minimally invasive surgery of the pancreas in progress.
AB  - BACKGROUND: Laparoscopic pancreatic surgery should be considered as an advanced
      laparoscopic procedure and should be performed only in institutions with
      experience in pancreatic surgery by a team with advanced laparoscopic skills.
      AIM: This review discusses the current status of the laparoscopic approach for
      inflammatory pancreatic diseases and for benign-appearing pancreatic tumors.
      RESULTS: Laparoscopic surgery has been shown to be beneficial in patients with
      inflammatory tumors located in the body-tail of the pancreas for chronic
      pancreatitis. Furthermore, patients with pancreatic pseudocysts may be managed
      with laparoscopic internal drainage (to the stomach, duodenum, or jejunum). Also,
      laparoscopic or retroperitoneoscopic necrosectomy has been used with success in
      patients with necrotizing pancreatitis. At present, laparoscopic surgery has
      proven to be beneficial in patients with cystic pancreatic neoplasms and
      neuroendocrine pancreatic tumors. CONCLUSIONS: The laparoscopic pancreatic
      approach was recently shown to be feasible and safe. Laparoscopy may contribute
      to reduced operation time and perioperative blood loss, and reduces surgical
      stress because of developments in devices, improvements in procedures, and
      advanced techniques.

PMID- 15999287
TI  - [Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes
      demonstrated by a case report].
AB  - A 34-year-old female patient with a three year history of generalized granuloma
      annulare was treated systemically with dapsone (DADPS). Six weeks after the onset
      of treatment, the patient developed an extensive tonsillitis of the base of the
      tongue with fever and malaise. Routine laboratory work showed a leukocytopenia
      with agranulocytosis. Further investigation revealed a marked decrease of the
      enzyme activity of N-acetyltransferase 2, which plays an important role in
      dapsone metabolism. Treatment included the cessation of dapsone, antibiotic
      coverage, and G-CSF leading to the rapid improvement of symptoms and
      normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a
      rare event and is interpreted as an idiosyncratic reaction. Depending on genetic
      polymorphisms of various enzymes, dapsone can be metabolized to immunologically
      or toxicologically relevant intermediates. Because of the risk of severe
      hematologic reactions, dapsone should only be employed for solid indications and
      with appropriate monitoring.

PMID- 15999291
TI  - The relationship between bone mineral density and biomechanics in patients with
      osteoporosis and scoliosis.
AB  - Nearly one-third of all women and one-sixth of all men over age 65 have
      osteoporosis, and this condition is often accompanied by lumbar scoliosis.
      Previous work has shown that, in a group of postmenopausal women with scoliosis
      and osteoporosis, both the bone mineral content (BMC) and bone mineral density
      (BMD) were greater on the concave side than the convex side. The goal of this
      study was to examine the structure-function relationships in the spines of
      patients with low bone mass and scoliosis using a patient-specific biomechanical
      model. We compared the percent change in BMC and the percent change in BMD with
      axial force, F(a), shear force, F(s), moment, M, local curvature, theta(rel), and
      the patient's age, A. We found that the percent change in BMC depended on the
      applied moment and the local curvature. The same dependence was observed for the
      percent change in BMD, but in this case, the shear force was also significantly
      inversely correlated. A population with femoral neck BMD with a T-score greater
      than -2.0 was similarly evaluated and yielded similar results. The percent change
      in BMD was related to M, theta(rel), A and negatively to the shear force. These
      results indicate that the osteoporotic spine is still able to respond to changes
      in the mechanical environment and provides a useful comparison between patients
      with osteoporosis and those with normal bone mass. In addition, this model may be
      a useful tool for the in vivo assessment of bone density changes in response to
      mechanical stimuli and drug treatments.

PMID- 15999292
TI  - Feasibility of in vivo structural analysis of high-resolution magnetic resonance
      images of the proximal femur.
AB  - Previously, high resolution MRI to assess bone structure of deep-seated regions
      of the skeleton such as the proximal femur was substantially limited by signal-to
      noise ratio (SNR). With the advent of new optimized pulse sequences in MRI at 1.5
      T and 3 T, it may now be possible to depict and quantify the trabecular
      microarchitecture in the proximal femur. The purpose of this study was to
      investigate the feasibility of assessing trabecular microstructure of the human
      proximal femur in vivo with MR imaging at 1.5 T and 3 T. MR images of six young,
      healthy male and female subjects were acquired using standard clinical 1.5-T and
      high-field 3-T whole-body MR scanners. Using a T2/T1-weighted 3D FIESTA sequence
      (and a 3D FIESTA-C sequence at 3 T to avoid susceptibility artifacts) a
      resolution of 0.234 x 0.234 x 1.5 mm(3) was achieved in vivo. Structural
      parameters analogous to standard bone histomorphometry were determined in femoral
      head and trochanter regions of interest. Bone mineral density (BMD) measurements
      were also obtained using dual-energy X-ray absorptiometry (DXA) for the femoral
      trochanter in the same subjects. The bone structure of the proximal femur is
      substantially better depicted at 3 T than at 1.5 T. Correlation between the
      structural parameters obtained at both field strengths was up to R =0.86 for both
      the femoral head and the trochanteric region. However, the resolution of the
      images limits the application of 3D structural analysis, making the assessment
      more akin to 2D textural measures, which may be correlated to histomorphometric
      but are not identical measures. This feasibility study establishes the potential
      of MRI as a means of imaging proximal femur structure, and improvements in
      technique and resolution enhancements are warranted.

PMID- 15999295
TI  - Mean hospital stay and treatment with electroconvulsive therapy.
AB  - INTRODUCTION: The objective is to analyze if the mean hospital stay is less than
      the episodes or not in which electroconvulsive therapy (ECT) is applied. METHODS:
      With a retrospective design, we studied a sample of 30 patients in whom ECT was
      applied between 1996 and 2001. These patients were suffering a disorder for which
      ECT has been shown to be effective (schizophrenia, bipolar disorder and major
      depression). Each one of the episodes (n = 185) of these patients was studied,
      comparing the length of stay in the hospital in these patients in which ECT was
      applied (n = 135) with those where it was not (n = 50). Statistical analysis was
      carried out by non-parametric Mann-Whitney-U tests. The descriptive level of
      statistical significance was established at p < 0.05. RESULTS: This work shows
      statistically significant differences between the treatment groups (p = 0.000),
      the length of stay being longer when ECT is applied.

PMID- 15999293
TI  - Lumbar bone mineral density in very long-term renal transplant recipients: impact
      of circulating sex hormones.
AB  - The influence of circulating sex hormones and gender on the bone mineral density
      (BMD) in long-term renal transplant recipients needs further investigation. We
      performed a retrospective analysis of lumbar BMD between 6 years and 20 years
      after renal transplantation. In 67 patients (47+/-12 years, 38 male) with a
      minimum interval of 72 months after transplantation, lumbar BMD measurements
      (dual energy X-ray absorptiometry) were performed (=complete cohort). Thirty-one
      patients (=longitudinal cohort) underwent at least three serial BMD measurements
      (mean follow-up 39+/-18 months, start at 86+/-22 months). All patients received
      prednisolone. In the complete cohort, BMD was significantly reduced in comparison
      to young healthy (mean T-score -1.33+/-1.40) and age-matched controls (mean Z
      score -0.91+/-1.45) at 88+/-31 months (p<0.05). Osteopenia or osteoporosis were
      present in two-thirds of patients. In the longitudinal cohort, a mean annual
      lumbar BMD loss of -0.6+/-1.9% was detectable equivalent to a -0.03+/-0.15
      reduction of Z-scores per year (regression analysis). Impact of hormonal status:
      In the complete cohort, postmenopausal status was associated with significantly
      lower BMD levels compared to men (p=0.0441). Women and men within the lowest
      tertile of sex hormone levels (LH, FSH, DHEAS, testosterone, progesterone,
      estradiol) did not exhibit significant differences in terms of lumbar BMD
      compared to those in the highest tertile. The mean annual bone loss was
      statistically indistinguishable between men and women. There was no significant
      correlation of sex hormone levels and BMD in men and premenopausal women. In
      postmenopausal women, however, low estradiol and high LH levels correlated with
      the extent of annual BMD loss (p<0.05). Our data confirm significantly reduced
      lumbar T-scores in the very late period after renal transplantation. The lumbar
      BMD decreased by -0.6+/-1.9% per year. In postmenopausal long-term renal
      transplant recipients, low estradiol levels were associated with accelerated bone
      loss.

PMID- 15999296
TI  - Serotonin gene polymorphisms in patients with panic disorder.
AB  - INTRODUCTION: The objective is to investigate the possible association between
      four serotonin gene polymorphisms (T102C, A-1438G, 5-HTTLPR and VNTR-5HTT) and
      panic disorder (PD). PATIENTS AND METHOD: 92 PD outpatients (DSM-IV criteria) and
      174 healthy volunteers from Asturias (control group) were included. Polymorphisms
      were determined after polymerase chain reaction amplification followed by
      digestion with restriction enzymes and electrophoresis on an agarose gel.
      RESULTS: Both 5-HT2A polymorphisms are in complete linkage disequilibrium in our
      population. No statistically significant differences in genotype frequencies of
      serotonin gene polymorphisms (T102C, A-1438G, 5HTTLPR and VNTR-5HTT) were found
      between patients and control subjects. Allele frequencies did not differ between
      both groups. No differences were found according to gender. CONCLUSIONS: The
      polymorphisms studied were not associated with PD in our population. However,
      larger patient samples are necessary to confirm or reject these findings.

PMID- 15999297
TI  - Validation of the Spanish version of the Social Functioning Scale.
AB  - INTRODUCTION: Social functioning as an outcome variable in therapeutic
      interventions with schizophrenic patients has been a relatively neglected area.
      The Social Functioning Scale (SFS) may be a good instrument to evaluate different
      therapeutical strategies for the rehabilitation of the schizophrenic patient. The
      aim of this paper is to validate the Spanish version of the SFS. MATERIAL AND
      METHODS: The Spanish version of the SFS was administered to 85 patients with
      schizophrenia (DSM-IV), and 120 healthy volunteers (60 unemployed and 60
      employed). RESULTS: Cronbach's alpha is between 0.69 and 0.80 in every subscale.
      Item-total correlations show higher internal consistency than in the validation
      of the original English version of the SFS. Factorial analysis suggests it could
      be appropriate to use a mean score from every subscale to make a total score.
      Discriminant analysis differentiates between patients and controls in a
      statistically significant way. In order to facilitate the interpretation of the
      results and their clinical use, a conversion of the direct scores into
      standardized ones was carried out. CONCLUSIONS: Results from three samples show
      that the Spanish version of the Social Functioning Scale is reliable, valid, and
      sensitive.

PMID- 15999298
TI  - Delusion as psychopathological metaphor.
AB  - The equivocity of the term delusion has led to it being considered a mere
      artifact. In this study, its meaning is considered as a psychopathological
      metaphor to be able to consider the relationships of man with the distorted
      reality. To do so, the meaning of the concept of man must be adequately
      understood, and based on this, observe the relationships that man establishes
      with reality. This relationship is always an aspiration to truth, although not
      exclusively as judicative as is usually understood. From this time, a series of
      apparently unconnected and rare psychopathological phenomena can be joined in
      view of the essentially veritative relationship. This relationship has been
      subjected to serious and deep philosophical considerations during the XX century
      and has left its mark on the psychopathological concept of delusion. This
      equivocity of delusion, finally dependent on a psychopathology that is understood
      in regards to an unsatisfactory idea of man, may be explained based on a better
      and more purified psycholopathological practice that is up-dated in regards to
      concepts of subjectivity and truth.

PMID- 15999299
TI  - Psychometric properties of the abbreviated Spanish version of TCI-R (TCI-140) and
      its relationship with the Psychopathological Personality Scales (MMPI-2 PSY-5) in
      patients.
AB  - INTRODUCTION: The short version of the Temperament and Character Inventory
      Revised (TCI-R), the TCI-140, is presented. This study aimed: a) to obtain the
      psychometric properties of TCI-140; b) to analyze the relationship with the
      normal version of the TCI-R, and c) to study its convergent validity with the
      MMPI-2 PSY-5. METHOD: The TCI-R and MMPI-2 PSY-5 scales were administered to a
      sample of consecutive psychiatric inpatients with differential Axis I and II
      diagnoses. RESULTS: It was found that the TCI-140 dimensions showed reliability
      coefficients ranging from 0.67 (Reward dependence [RD]) to 0.86 (Self
      Transcendence [ST]) and the reliability coefficients of PSY-5 ranging from 0.68
      (CON) to 0.86 (NE/NEU). Correlations for the dimensions with the TCI-R original
      240-item version and TCI-R 140 item version ranged from 0.91 (Self-Directedness
      [SD]) to 0.97 (ST). The dimensions had a normal distribution. Correlations of TCI
      140 scales with PSY-5 scales provided preliminary evidence supporting the
      convergent validity of the constructs. Then, Novelty Seeking (NS) was associated
      with low Constraint, Harm Avoidance (HA) was associated with low Aggressiveness
      and Positive Emotionality/ Extraversion, and also with high Negative
      Emotionality/Neuroticism, Reward Dependence (RD) was associated with high
      Positive Emotionality/Extraversion. Persistence (PS) was related to high
      aggressiveness, and Positive Emotionality/ Extraversion. On the other hand, SD
      was correlated with low Psychoticism, and Negative Emotionality/Neuroticism, and
      also with high Positive Emotionality/Extraversion. Cooperativeness (C) had a
      relationship to high constraint and low psychoticism. Finally ST was associated
      with high psychoticism and Positive Emotionality/Extraversion. CONCLUSIONS: The
      short Spanish version of TCI-R is a useful inventory for the evaluation of the
      principals dimensions of temperament and character.

PMID- 15999300
TI  - Mental disorders and the internal armed conflict in Guatemala.
AB  - INTRODUCTION: The Guatemalan society was exposed to an internal armed conflict
      during the period from 1962 to 1996. During these years, the civil society
      suffered multiple traumatic events. The objective of this study is to understand
      the psychological impact that the conflict had on the mental health of the
      Guatemalans. METHODS: A review of articles published between 1962 and 2004, in
      the databases Medline, Lilacs, Embase, Psiclit-Infon, Cochrane Library and Pilots
      was conducted. The articles that were selected found mental disorder prevalences
      in Guatemalans through standardized instruments. RESULTS: Eight studies were
      found to demonstrate, in general, elevated prevalences for mental disorders in
      different population groups affected by the violence. For the depression ranges,
      the prevalence was between 38.8% and 41.8%; for anxiety symptoms intervals
      between 27.7% and 54.4 %; for sleep problems, 75 %, and for posttraumatic stress
      disorder (PTSD) studies with low frequencies from 2% to 11.8 % and other studies
      that demonstrated higher prevalences from 32% to 52%. CONCLUSIONS: These mental
      disorders prevalences can be interpreted as elevated when compared with
      population studies of persons not exposed to armed conflicts where the PTSD
      ranges generally go from 0.5% to 11.7%. This permits the inference that these
      high frequencies are probably related to traumatic experiences of the war in
      Guatemala and in exile.

PMID- 15999301
TI  - Diagnostics discrepancies between ICD-10 and DSM-IV in personality disorders.
AB  - INTRODUCTION: 50 % of the patients seen in the mental health clinics have
      personality disorders and their diagnosis is very important to establish the
      patient's prognosis and treatment. The clinician usually only uses one nosology,
      the ICD-10 or the DSM-IV and is aware of the differences between them. However,
      he/she gives preference to his/her favorite nosology. MATERIAL AND METHOD: A
      total of 248 patients seen in a mental health clinic were included in the study.
      They were diagnosed of anxiety (n = 121) and depressive (n = 127) disorders, with
      a mean age of 32.3 years for anxiety disorders and 32.4 years depressive
      disorders. The International Personality Disorders Examination (IPDE) Screening
      Questionnaire in its DSM-IV and ICD-10 versions was administered to observe the
      degree of concordance between the two nosologies. RESULTS AND DISCUSSION: The
      female population predominated in our sample, these being 35.5 % men with anxiety
      disorders and 65,5 % women, and 29.10 % men and 70.9 % women with depressive
      disorders. An observational study was performed by studying the percentage with 3
      or more positive items and also percentage with 6 or more positive items. It was
      observed that the DSM-IV version produced more positive diagnoses and more
      comorbidity. Thus, it is necessary to consider whether the ICD-10 version
      subdiagnoses personality disorders or the DSM-IV version gives false positives.
      The qualitative differences between the ICD-10 and the DSM-IV must also be
      considered. The ICD-10 does not include narcissistic and schizotypal personality
      disorders and subdivides the borderline personality disorder into two
      subcategories, so that a given patient can receive different diagnoses according
      to the nosology used. CONCLUSIONS: In the patient sample studied, diagnostic
      discrepancies in personality disorders between DSM-IV and ICD-10 are so important
      that the World Health Organization and the American Psychiatry Association should
      consider unifying categories and diagnostic criteria of personality disorders in
      the next nosologies.

PMID- 15999302
TI  - Proposal of a dimensional model of personality disorders.
AB  - During recent years there has been a growing interest on several aspects
      regarding psychopathology in general and particularly with personality disorders,
      such as dual psychopathology, comorbidity and dimensional models. Going from the
      Eysenck's three-factor model to the Fiske's five-factor one, from the Cloninger's
      psychobiological model to the Millon's biosocial one, a wide variety of
      personality analysis models, as well as dimensions to which the different
      personality disorders should be anchored, have been proposed. Here, we propose a
      dimensional model for personality disorders based on DSM-IV criteria, which are
      cognitive style (field dependence-independence), prevalent emotion (anger-fear),
      interpersonal style (submissiveness-dominance), and impulse control
      (impulsiveness-compulsiveness). We consider that these dimensions are related to
      different levels of cerebral complexity, assuming that evolution operates under
      the redundancy principle. Based on these dimensions, a bimodal model in which
      antisocial personality (high field dependence, anger, dominance, and
      impulsiveness) and schizotypal personality (low field dependence, fear,
      submissiveness, and compulsiveness) would be anchored in each extreme is
      proposed. Between these two extremes, the rest of personality disorders, such as
      borderline, paranoid, narcissist, histrionic, dependent, passive-aggressive,
      avoidant, obsessive-compulsive, paranoid, and schizoid, would be anchored.

PMID- 15999303
TI  - Living for illness: a case report of schizophrenia diagnosed at the age of 63.
AB  - Hidden psychiatric morbidity represents an important problem, one to two-thirds
      of serious cases receiving no treatment each year, often due to lack of awareness
      of illness. We present a case report of a patient diagnosed of schizophrenia
      whose first contact with the health system occurred at the age of 63 in extreme
      social circumstances.

PMID- 15999304
TI  - Diagnostic categorization of post-abortion syndrome.
AB  - Some psychopathological characteristics are frequently observed in women who have
      voluntarily aborted. However, some resistance currently remains to their
      recognition as a differentiated nosological category, known as Post-Abortion
      Syndrome (PAS). We tried to assign a diagnostic category to women with PAS by
      determining the extent by which they fulfilled the diagnostic criteria of
      international classifications. Criteria for Post-Traumatic Stress Disorder (PTSD)
      were met in the ten PAS cases studied. In addition, patients also showed other
      non-specific symptoms such as repeated and persistent dreams and nightmares
      related with the abortion, intense feelings of guilt and the "need to repair".
      PAS should be considered as an additional type of PTSD. It also has some specific
      characteristics that could help to understand the patient's life experience and
      to establish a psychotherapeutic intervention.

PMID- 15999305
TI  - Advanced paediatric laparoscopic surgery: repetitive training in a rabbit model
      provides superior skills for live operations.
AB  - TOPIC: The rapid development of advanced laparoscopic techniques is a strong
      challenge for the skills and competence of the paediatric surgeon. It is
      therefore mandatory that training must offer adequate preparation. The present
      experimental study investigates how surgical residents perform laparoscopic bowel
      biopsy and defect repair after training with a pelvitrainer versus a rabbit
      model. METHODS: New Zealand white rabbits, 3 mm instruments, a 5 mm scope and a 6
      - 0 prolene suture were used. Twelve surgical residents were randomised into two
      groups. Their basic task was to take a seromuscular bowel biopsy laparoscopically
      and to repair the defect using an intracorporeal suture. Group I trained 8 times
      (on 8 occasions) with a pelvitrainer (PT), group II trained similarly using a
      rabbit model (RM). Each participant took a final test to demonstrate the
      operation in the rabbit. Operating time, suture time and perforation of the bowel
      were analysed. RESULTS: In the PT group, mean operating times decreased from
      11.18 (+/- 5.04) min to 4.91 (+/- 0.89) min (p < 0.01), however the final test
      procedure in the rabbit model lasted 9.62 (+/- 5.11) min. In the RM group mean
      operating times also decreased from 10.04 (+/- 3.39) min to 6.38 (+/- 1.40) min
      (p < 0.01) during the eight training operations. Within this group the final live
      operation lasted 5.45 (+/- 0.67) min and was significantly faster than in the PT
      group 9.62 (+/- 5.11) min (p < 0.1). The suture times showed a similar pattern. A
      significant difference with respect to the rate of perforation was not found.
      CONCLUSIONS: Repetitive training in the rabbit provides superior skills for live
      operations. In paediatric surgical centres with advanced laparoscopic procedures,
      an animal model should be considered as an important step in training which may
      contribute to a beneficial outcome in patients.

PMID- 15999306
TI  - An abnormal distribution of C-kit positive cells in the normoganglionic segment
      can predict a poor clinical outcome in patients with Hirschsprung's disease.
AB  - PURPOSE: The loss or decrease of interstitial cells of Cajal (ICCs) has been
      implicated in several disorders of human intestinal motility. We have encountered
      a few cases suffering from severe constipation or enterocolitis resulting in
      patient death after a definitive operation for HD, even though the
      normoganglionic intestine had been successfully pulled through. We investigated
      the distribution of ICCs using c-kit immunostaining in the normoganglionic
      segment and compared these findings with the clinical outcome after a definitive
      operation in each case. PATIENTS AND METHODS: The distributions of ICCs were
      investigated by using c-kit immunostaining in the normoganglionic segment in the
      resected bowel in 15 cases with HD. The distributions of protein gene product 9.5
      (PGP 9.5) as a general neuronal marker and those of NADPH-diaphorase (NADPH-d) as
      a marker of nitric-oxide neurons were also examined. The numbers of ICCs and
      neurons were evaluated quantitatively. The histopathological results were
      compared with the clinical outcome after definitive operation in each case.
      RESULTS: C-kit immunoreactive cells showed a normal distribution in the
      normoganglionic segment in 13 cases, while they were markedly (less than 50%
      compared with the other cases) decreased in 2 cases. The distributions of PGP 9.5
      and NADPH-d were almost the same in all cases. The bowel movements of 13 cases
      showing normal c-kit distribution were satisfactory. In contrast, the bowel
      movements were impaired in 2 cases with a decreased number of c-kit positive
      cells. One infant suffered from severe persistent constipation and thus had to
      undergo a resection of a dilated colon. The other infant died of sepsis due to
      postoperative enterocolitis and showed a markedly dilated colon. CONCLUSION: A
      decreased number of c-kit positive cells in the normoganglionic segment can thus
      allow us to predict a poor clinical outcome after definitive surgery, probably
      due to poor intestinal motility. Therefore examining the c-kit distribution in a
      resected bowel specimen in patients with HD should be mandatory in order to
      select the optimal postoperative treatment regimen for each case.

PMID- 15999307
TI  - Topographic peculiarities of the submucous plexus in the human anorectum-
      consequences for histopathologic evaluation of rectal biopsies.
AB  - Chronic colorectal motility disorders are commonly encountered in the pediatric
      population. While most cases can be managed successfully by conservative therapy,
      a subgroup of patients suffers from severe constipation and requires further
      diagnostic procedures to identify the underlying pathologies, such as
      aganglionosis, hypoganglionosis or intestinal neuronal dysplasia (IND). The
      present study provides reference data about the quantitative distribution of
      nerve cells and ganglia within the submucosal plexus of the human anorectum from
      healthy subjects. Anorectal specimens (n = 15) obtained postmortem were divided
      into 6 segments beginning from the dentate line (S1 = 0-2 cm, S 2 = 2-4 cm, S3 =
      4-6 cm, S4 = 6-8 cm, S5 = 8-10 cm, S6 = 10-12 cm). From each segment sections (6
      microm thickness) were immunostained with a pan-neuronal marker (Protein Gene
      Product 9.5) to visualize the enteric nervous system. A morphometric analysis was
      carried out for each segment recording the number of ganglia and nerve cells of
      the submucous plexus. Neither ganglia nor nerve cells showed a uniform
      distribution pattern, but decreased continuously towards the anus. However, even
      the lowest segments (S1, S2) contained nerve cells and were not aganglionic. In
      the remaining segments ganglia with 7 or more nerve cells could be detected. The
      findings demonstrate segment-specific quantitative differences of the anorectal
      submucous plexus which should be taken into consideration for the histopathologic
      evaluation of rectal biopsies. Moreover, the data support the concept of a
      physiologic hypoganglionosis of the anal canal.

PMID- 15999308
TI  - Matrix testing for urothelial tissue engineering.
AB  - INTRODUCTION: Surgical reconstruction of the bladder is associated with many well
      known complications. Tissue engineering is under discussion as a potential
      therapeutic strategy and many of the proposed benefits are of special interest
      for children. Biomaterials play a key role in tissue engineering. Many materials
      have been proposed for the experimental reconstruction of the bladder and
      urethra. They determine the biological and mechanical characteristics of the
      reconstructed tissues. Most publications focus on a single material. In order to
      identify the most suitable biomaterial it was the aim of this study to compare
      biological and mechanical features of different biomaterials seeded with
      urothelial cells in vitro. MATERIALS AND METHODS: Commercially available
      biomaterials (Biogide, Ethisorb, Lyoplant, SIS, Vicryl, Xenoderm) of biologic or
      synthetic origin were seeded with urothelial cells. Cell-matrix constructs were
      cultured and investigated by scanning electron microscopy for surface structure
      and cell morphology. They were also subjected to extension until failure and the
      force required was reported as f (max). Values obtained and curve shape were
      compared to specimens of bladder mucosa and submucosa. RESULTS: Cell adhesion and
      morphology showed marked differences between materials. Cell shape varied from
      single spherical cells to confluent layers of flat urothelium. f (max) ranged
      from 0.02 N to 48.86 N for tested materials and 1.19 N for native bladder
      mucosa/submucosa. DISCUSSION: The materials showed marked differences in
      biological and mechanical features in vitro. Cells cultured on biogenic matrices
      were more similar to native urothelium. Most of the tested materials showed
      different curve shapes and higher f (max) values than native bladder mucosa.

PMID- 15999309
TI  - Cutaneous vesicostomy revisited--the second 15 years.
AB  - The aim of this paper was to review the authors' experience with cutaneous
      vesicostomy (CV) over the last 15 years including indications, results, and
      complications of CV. MATERIALS AND METHODS: The records of 31 patients treated by
      CV between 1987 and 2002 were reviewed. There were 20 boys and 11 girls. The two
      main primary pathologies were neuropathic bladder (19 patients) and posterior
      urethral valve (PUV) (7 patients). All patients underwent a Blocksom-type
      operation at a mean age of 23 months (range 14 days-9 years). Pre- and
      postoperative conventional uromanometry was performed in 18 patients (58%) and
      bladder function was assessed. RESULTS: In 23 patients (74%) the CV provided a
      successful diversion with improvement of the upper urinary tract and/or
      stabilization of the renal function. In 5 patients (16%) with PUV, the
      improvement was temporary. In 3 patients (10%) the CV did not result in an
      improvement. Twenty-four patients underwent CV closure after a mean duration of
      23 months (range, 1 month-7 years) of diversion. In 2 patients with
      myelomeningocele (MMC) and severe somato-mental developmental delay, CV was not
      closed and is being considered as a permanent treatment option. Urodynamic
      studies in 5 PUV patients showed impaired compliance and high intravesical
      pressure following a successful valve ablation and closure of CV. In the
      neuropathic bladder group the bladder function improved following closure of CV
      and commencement of anticholinergic medication and clean intermittent
      catheterization (CIC). Our augmentation ratio in the neuropathic bladder group
      was 22%. Complications of CV included: stenosis in 7 patients (22%), prolapse in
      2 (6%), and cellulitis in 2 (6%). The revision rate was 16%. CONCLUSIONS: In
      young infants CV had a less favourable result in the PUV patients than in cases
      with high-pressure neuropathic bladder with upper tract dilatation and severe
      urinary tract infection (UTI), where CV provided decompression and prevented
      deterioration of the renal function. Cutaneous vesicostomy has stood the test of
      time in our changing paediatric urological practice and it remains a valuable
      weapon in the armoury of paediatric urologists in selected patients.

PMID- 15999310
TI  - Myogenesis within the human gubernaculum: histological and immunohistochemical
      evaluation.
AB  - BACKGROUND: The presence of varying amounts of smooth muscle (SM) in the patent
      processus vaginalis suggests that SM plays a role in the descent of the testis.
      Myogenesis within the gubernaculum (representing primitive mesenchymal tissue)
      has been evaluated. MATERIALS AND METHODS: Bilateral gubernacula of ten male and
      five female fetuses were obtained. Sections were stained with hematoxylin-eosin,
      van Gieson and Gomori trichrome. Expressions of human muscle actin, desmin,
      vimentin, alpha-smooth muscle actin, human myosin, fast myosin, slow myosin, and
      Myo-D were determined through immunohistochemistry. The structural alterations
      and expressions according to the fetal ages were determined within the
      gubernacula of both sexes. RESULTS: Gubernacula revealed striated muscle at
      twelve weeks of age. Despite expression of actin and desmin, those muscles did
      not express Myo-D. Actin and desmin expressing striated muscles ceased to exist
      until 22 weeks of age. Both vascular SM and cremaster muscle (CM) expressed Myo-D
      during the 22nd and 23rd weeks. CM additionally expressed alpha-smooth muscle
      actin. Detection of myofibroblasts in the 22nd week was followed by appearance of
      the SM in the 27th week in the gubernacula of male fetuses. The same alterations
      were encountered among the female fetuses at later time points. CONCLUSION: Both
      smooth muscle and CM develop within the gubernaculum. CM may have
      transdifferentiated from the vascular SM. If the gubernaculum represents
      primitive mesenchymal tissue, it ceases to exist after the development of
      muscles.

PMID- 15999311
TI  - Acute epididymitis in children: a 4-year retrospective study.
AB  - OBJECTIVE: To evaluate the incidence of acute epididymitis (AE) compared to
      testicular torsion (TT) as a form of acute scrotum in children, to describe
      clinical aspects and to assess the value of laboratory tests and radiological
      investigations in AE. METHODS: Retrospective review of the medical records of 49
      patients presenting with clinical aspects of AE over a 4-year period; evaluation
      of clinical features, laboratory tests (blood, urine), radiological examinations
      (duplex and real-time ultrasound, renal sonography, voiding cysturethrography
      [VCUG]) and urodynamics. RESULTS: 49 patients with an overall mean age of 9.8
      years (range 0.2-15.3 years) presented with AE. In the same period, 31 subjects
      required surgery for TT. Local pain on palpation of the epididymis and
      spontaneous pain in the testis and/or epididymis were the most common clinical
      signs. In 2 patients, urine cultures revealed significant bacteriuria. Duplex and
      real-time ultrasound showed no false negative result. 41% of the patients
      revealed concomitant urological diseases, but only in 1 patient was treatment
      influenced by the uropathy. 16/21 older boys (76%) demonstrated normal uroflow
      patterns. CONCLUSION: AE seems to be more common than acute TT. Urinalysis and
      urine culture should be performed for all children with AE. High resolution
      ultrasound with an experienced investigator is able to exclude TT reliably so
      that routine surgical exploration is seldom necessary.

PMID- 15999312
TI  - Use of an artificial dermis (Integra) for the reconstruction of extensive burn
      scars in children. About 22 grafts.
AB  - We used an artificial dermis (Integra) for the reconstruction of extensive burn
      scars in children. Integra was initially developed for the primary coverage of
      acute burns, but several authors report good experiences with Integra for
      reconstructive surgery. We present a group of 10 children who underwent Integra
      grafting at 22 different operational sites. Five children received several grafts
      with Integra. On average, 260 cm(2) per session were grafted. We compared the
      surface of Integra on the day of grafting and then again on the evaluation day to
      measure the secondary retraction of the grafts. Complications (infection of
      Integra, failure of the epidermal graft) were observed in 5 cases. At the final
      evaluation, 20 grafts were visible. The surface of the Integra graft represented
      less than 50% of the initial surface in 7 cases, 51-75% in 5 cases and more than
      76% in 8 cases. The disadvantages of Integra in reconstructive surgery are that
      two operative procedures are necessary and the recurrence of contraction seems to
      be more significant than with full thickness auto grafts. However, Integra has
      many advantages: the immediate availability of large quantities, the simplicity
      and reliability of the technique, the pliability and the cosmetic aspect of the
      resulting coverage. In light of these preliminary results, Integra appears to
      offer a new alternative for the reconstruction of extensive burn scars in
      children.

PMID- 15999313
TI  - Solitary liver abscess in a healthy child presenting with fever of unknown
      origin.
AB  - Pyogenic liver abscess is rarely encountered in normal children. We report a case
      of solitary pyogenic liver abscess in a healthy child aged 8 months. He presented
      with fever of unknown origin and mild hepatomegaly. Full recovery was achieved by
      surgical intervention and prolonged antibiotic treatment. Management and
      recommended treatment in children with liver abscess are presented.

PMID- 15999314
TI  - A sporadic abdominal desmoid tumour case presenting with intermittent intestinal
      obstruction.
AB  - Desmoid tumours, also known as aggressive fibromatoses, are rare lesions having
      intermediate biological behaviour between benign fibrous lesions and
      fibrosarcomas. Although abdominal desmoids have an increased incidence in
      Gardner's syndrome, they are rarely found in isolated form. We report a barium
      study, ultrasound, computed tomography and magnetic resonance imaging findings of
      a case in a nine-year-old boy with intermittent nausea and vomiting. Although
      intraabdominal desmoids are usually detected as a solitary lesion in sporadic
      cases, the case presented here had two mesenteric lesions in the left upper
      quadrant. Intestinal obstruction and invasion of colon wall had occurred.

PMID- 15999315
TI  - Traumatic aneurysm of the bifurcation of the abdominal aorta in an infant. A case
      report.
AB  - Post-traumatic aneurysms are extremely rare in the infant population. We report a
      case of delayed abdominal aortic aneurysm that appeared in a 5-year-old female,
      admitted 5 months previously with contusions to the abdomen.

PMID- 15999316
TI  - Infarction of an accessory spleen presenting as acute abdomen in a neonate.
AB  - An accessory spleen is a relatively common condition, but the torsion thereof is
      extremely rare, with only nine pediatric cases reported in the literature. This
      paper describes a case of an accessory spleen that was found to be necrotic
      during an emergency laparotomy in a 14-day-old female infant with signs of acute
      abdomen. To our knowledge, this is the youngest reported patient. The etiology of
      the necrosis was thrombosis of its trophic vessels, secondary to its pedicle
      torsion. The literature is also reviewed.

PMID- 15999317
TI  - Ectopic thoracic kidney in a child with congenital diaphragmatic hernia.
AB  - Thoracic ectopic kidney with partial or complete renal protrusion above the level
      of the diaphragma into the posterior mediastinum is the rarest form of all
      ectopic kidneys with an incidence of less than 1 per 10,000 cases. We present a
      newborn with right congenital diaphragmatic hernia associated with thoracic
      ectopic kidney. The diagnosis of ectopia was made prior to surgery. Gerota's
      fascia of kidney was used to close the diaphragmatic defect. Since this renal
      anomaly is usually asymptomatic, it does not require any specific treatment.
      However, a close examination of function and anatomy of the kidney prior to
      surgery of hernia is important and beneficial. We discuss the embryological
      context and the importance of renal scintigraphy in patients with ectopic kidney.

PMID- 15999318
TI  - Adenocarcinoma of the rectum in childhood following chemotherapy and radiotherapy
      for a rhabdomyosarcoma--a case report.
AB  - We report a case of rectal adenocarcinoma in a 9-year-old boy, which took the
      form of a second malignant neoplasm following treatment for an early childhood
      malignancy. The abdominal complaints were for a long time interpreted as an
      infectious disease. At the time of diagnosis of the rectal carcinoma, the tumor
      had already progressed to the stage of metastatic disease. Therapy consisted of
      deep anterior rectal resection and regional arterial chemotherapy for liver
      metastases. The child died 18 months after the diagnosis of rectal carcinoma. As
      survival for childhood tumors improves, rare second malignant neoplasms will
      become increasingly common in children and adolescents. This phenomenon
      emphasizes the need for continued clinical surveillance of patients who have been
      treated with chemotherapy or irradiation for childhood tumors. The increased risk
      of second malignant neoplasms and an early onset of adult-type tumors has to be
      considered.

PMID- 15999319
TI  - Solitary rectal ulcer syndrome in children. A report of three cases.
AB  - Solitary rectal ulcer syndrome (SRUS) is a rare condition in children. It is well
      recognised in the adult literature. We report our experience with 3 patients; two
      boys presented at a very young age (18 and 24 months, respectively) with a
      clinical picture simulating inflammatory bowel diseases. The other patient was a
      fifteen-year-old girl presenting with severe rectal stricture as a result of the
      syndrome, which is the first to be reported in the paediatric literature.

PMID- 15999320
TI  - Report of an uncommon cluster of septic arthritis of the hip in premature
      newborns: three cases in a period of 3 months.
AB  - We report an uncommon cluster of this rare condition which occurred within a very
      short period of time in our unit. We reviewed the current literature and observed
      that the diagnosis is often delayed, which can have very serious consequences for
      the outcome. Our 3 patients have had an uncomplicated course so far and follow-up
      examination at almost one year was normal. A high index of suspicion for the
      diagnosis and early and aggressive treatment is necessary.

PMID- 15999321
TI  - Gastric outlet obstruction: the role of H. pylori infection concomitant with
      ectopic pancreatic tissue.

PMID- 15999322
TI  - [Surgery for temporal-lobe epilepsy].

PMID- 15999323
TI  - [Pharmacoresistant temporal-lobe epilepsy. Exploration with foramen ovale
      electrodes and surgical outcomes].
AB  - AIM: To report our experience in the surgical treatment of temporal-lobe
      epilepsy. PATIENTS AND METHODS: An analysis was performed of the outcomes of 137
      patients submitted to surgery between 1990 and 2001, with a follow-up of more
      than two years. A study was conducted of the percentages of successful detection
      by the different complementary tests--MRI, EEG, interictal SPECT, video-EEG with
      foramen ovale electrodes (FOE), neuropsychological study (NPS)--and the precision
      with which they reported the epileptogenic focus. RESULTS AND CONCLUSIONS:
      Successful surgical outcomes (Engel grades I-II): 73.4%. No surgical mortality
      occurred, although some mild, reversible morbidity was observed. Surgical
      outcomes were not affected by sex, age, age of onset and the length of time the
      patient had had the disease, or the frequency of the seizures. No association was
      found between seizures in the immediate post-operative period and a poorer long
      term control of the epilepsy. MR images were normal in 25% of patients; in these
      cases the surgical outcomes (Engel grades I-II at two years: 62%) were
      significantly poorer than in cases of tumours/cavernomas (86%); RMI studies of
      other types of lesions gave intermediate results (72%). With respect to the
      capacity of the different tests to lateralise/locate the epileptogenic focus,
      video-EEG-FOE proved to be the best, followed by MRI, SPECT, EEG and NPS.

PMID- 15999324
TI  - [Variability in the treatment of headaches in visits to the Neuropaediatrics
      service at six Spanish hospitals].
AB  - INTRODUCTION: Headache is one of the chief reasons for visiting Neuropaediatric
      units. Variability in clinical practice has been defined as variations in the
      rates a clinical procedure is employed. The aim of this work is to study the
      variability in the treatment of children's headaches in six Spanish hospitals.
      PATIENTS AND METHODS: We conducted a retrospective study involving patients who
      first visited because of a headache some time in the year 1999. Data were
      collected in December 2003. The following variables were analysed: type of
      headache, neuroimaging scans, beginning of prophylaxis, follow-up visits to
      clinic and number of patients who dropped out of the follow-up. RESULTS: In all,
      372 children were attended. 63.4% of the headaches were considered as being
      migraine-type; 43% of the patients were submitted to neuroimaging and prophylaxis
      was established in 36.8%. Mean follow-up time in the clinic was 10.6 months and
      the mean number of visits was 3. 30% had dropped out of the follow-up. In the
      comparative analysis, significant differences were found in all the variables
      studied. CONCLUSIONS: Overall results are similar to those found in other series.
      The differences found between centres can be accounted for by differences in
      population, differences in health professionals' styles of medical practice or by
      the nonexistence of clear guidelines regarding a particular procedure.

PMID- 15999325
TI  - [The value of quantitative electroencephalogram analysis in the study of
      dementias].
AB  - INTRODUCTION: The question as to whether an electroencephalogram (EEG) needs to
      be carried out as a preliminary study in patients with dementia is currently the
      subject of some controversy. AIMS: Our aim was to determine the value of
      conventional and quantitative analysis of EEG recordings in the treatment of
      dementia. PATIENTS AND METHODS: The EEG recordings of patients diagnosed with a
      syndrome of dementia were analysed both visually and quantitatively (comparing
      them with patients with major depressive disorder). RESULTS: A total of 45 EEG
      traces were analysed -25 from patients with dementia and 20 with major depressive
      disorder-. The most significant finding was the number of abnormal recordings in
      each group, which was higher in the dementia group, with 19 abnormal recordings
      (76%) versus five in the depression group (25%). The difference was statistically
      significant (p = 0.001). The slow base rhythm and low voltage also differed
      notably between the two groups. The two groups displayed significant differences
      in both the frontal d and the temporal q rhythms (relative power), although the
      percentage was higher in patients with dementia. The posterior a rhythm was the
      variable with the greatest difference, and the percentage was higher in patients
      with depression. In absolute power, only the posterior a rhythm displayed a
      significant difference between the two groups, and was greater in the patients
      with depression. CONCLUSIONS: Performing an EEG in the initial treatment of
      patients with dementia is useful to distinguish it from other pathological
      conditions, and its quantitative analysis helps in the search for the focus.

PMID- 15999326
TI  - [Amnesic stroke caused by hippocampal infarction].
AB  - INTRODUCTION: The term amnesic stroke is used to describe a condition in which
      the dominant symptom is a relatively persistent acute amnesia of a vascular
      origin. It may appear in cases of lesions in the posterior cerebral artery (PCA),
      thalamic arteries and anterior choroidal artery, and clinical reports describing
      this condition are scarce. CASE REPORT: We describe the case of a 77-year-old
      male with vascular risk factors who presented sudden onset mnemonic deficit that
      affected basic activities of daily living, and apathy. Examination of the patient
      revealed an anterograde episodic amnesia with an inability to retain new
      information and short-term memory was also clearly affected, although access to
      old memories remained relatively intact. There was no other sensory-motor focus.
      A CAT scan showed a right-side sylvian infarction and hypodense areas in both
      hippocampuses. The neuropsychological evaluation revealed global amnesia: CME (in
      Spanish, MEC) 17/30; working memory with CME 7/27; SVF (animals): 7; the 7-minute
      test (visual/verbal memory: free recall 2/16, facilitated 9/16); clock test: 3/9.
      Later progression was good, with recovery of short-term memory and the capacity
      to retain concepts, and the patient was again able to perform the activities he
      previously carried out. CONCLUSIONS: There are three amnesic stroke syndromes
      with different semiological characteristics, depending on the vascular territory,
      that is, the PCA, thalamic arteries and anterior choroidal artery. In this case,
      the most striking points are the more intense disorders affecting short-term
      memory and retention, with relative conservation of long-term memory, and the
      location of the stroke in the hippocampus. Its good outcome allows it to be
      distinguished from vascular dementia.

PMID- 15999327
TI  - [Recurrent Tolosa-Hunt syndrome with normal neuroimaging. A report of three
      cases].
AB  - INTRODUCTION: Tolosa-Hunt syndrome is caused by an unspecific inflammation in the
      cavernous sinus or superior orbital fissure. Recurrence occurs in 40% of cases.
      Magnetic resonance (MR) of the head and orbital phlebography can reveal
      characteristic data, although diagnosis is reached by exclusion according to
      International Headache Society criteria. Corticoids are the preferred treatment,
      since their use gives rise to the disappearance of the clinical condition in a
      few days. CASE REPORT: We describe the cases of three patients with recurrent
      Tolosa-Hunt syndrome and MR images of the head with normal contrast. Case 1: a 52
      year-old male with paralysis of the oculomotor nerve with recurrence on the
      contralateral side. Case 2: a 42-year-old female with recurrent paralysis of the
      abducent nerve. Case 3: a 34-year-old male with involvement of the oculomotor
      nerve, optic nerve and the first branch of the trigeminal nerve with recurrence
      of the ophthalmoplegia. In all cases the clinical symptoms disappeared with the
      use of corticoid therapy. CONCLUSIONS: The oculomotor disorder is produced by
      nerve infiltration and not by compression. The time for recurrence varies
      largely, and the clinical condition in the recurrence is usually milder owing to
      the fact that diagnosis is reached and treatment is started earlier. The absence
      of alterations in the MR of the head does not rule out the existence of Tolosa
      Hunt syndrome, even in cases of recurrence, and these disorders therefore should
      not be included in the diagnostic criteria.

PMID- 15999328
TI  - [Idiopathic hypertrophic cranial pachymeningitis diagnosed after venous
      thrombosis].
AB  - INTRODUCTION: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare
      and little known form of chronic inflammation of the dura mater, the pathogenesis
      of which remains unclear. CASE REPORT: We report the case of a 77-year-old male
      who was admitted to hospital after suffering a stroke; following the findings in
      the MR imaging, the patient was diagnosed as having IHCP. Treatment with
      corticoids led to an improvement in the patient's condition both clinically and
      radiologically. CONCLUSIONS: IHCP produces a non-nodular diffuse dural thickening
      that is hypointense with respect to the brain parenchyma in all the MRI sequences
      with intravenous contrast enhancement.

PMID- 15999329
TI  - [FOXP2: from the specific disorder to the molecular biology of language. II.
      Implications for the ontogenesis and phylogenesis of language].
AB  - INTRODUCTION: Cloning FOXP2, the first gene linked to a hereditary variant of
      specific language impairment (SLI), has allowed researchers to conduct more
      precise studies into the nature and developmental path of the molecular bases
      governing the organisation and functioning of the neuron centres responsible for
      language processing. DEVELOPMENT: The FOXP2 gene codes for a transcriptional
      repressor that regulates the proliferation and/or migration of certain neuronal
      populations in the basal ganglia, cortex, cerebellum and thalamus, and presumably
      plays a part in the organisation and/or functioning of the fronto-thalamic
      striatal system. Moreover, the analysis of the developmental history of the gene
      suggests that the transcriptional factor FOXP2, although it is quite old, has
      undergone certain modifications in its secondary structure and has acquired a
      potential site for phosphorylation for protein kinase C during the recent
      developmental history of the human species. CONCLUSIONS: The evidence discussed
      in this article allows us to suggest FOXP2 plays a significant role in the
      ontogenetic and phylogenetic development of language. On the one hand, it seems
      to validate certain general models of linguistic processing that call for a more
      important role of the subcortical structures (above all for the basal ganglia) in
      that processing. On the other hand, it seems to suggest that the modifications
      undergone by FOXP2 would have also allowed certain regions (such as Broca's area)
      to be recruited for language, either by facilitating the appearance of syntax
      and/or verbal working memory or by transferring control of articulation to those
      regions, thereby laying down the foundations for the appearance of spoken
      language.

PMID- 15999330
TI  - [The clinical and economic impact of generic drugs in the treatment of epilepsy].
AB  - AIMS: The aim of this study was to determine whether the introduction of generic
      formulations of antiepileptic drugs (AED) would lead to an economic saving for
      the public health service. DEVELOPMENT: The narrow therapeutic index, low
      solubility and non-linear pharmacokinetics of some AED mean that the ranges of
      bioequivalence that are authorised for generic formulations do not offer the same
      results regarding effectiveness and safety as those obtained by brand name drugs.
      This is why the potential saving stemming from the use of generic AED may be
      exceeded by the costs deriving from the consequences conditioned by their
      utilisation. These are the conclusions that can be drawn from the results of cost
      and effectiveness analyses conducted on two hypothetical cases of substituting (9
      and 20%) treatments involving brand name carbamazepine (CBZ) with generic
      formulations. If a generic CBZ were introduced into the treatment of 9% of the
      patients taking this drug, the annual cost for one person with epilepsy would
      rise by 38.17 as compared to treating all these patients with brand name CBZ
      (marginal cost-effectiveness), and overall spending on health care in the country
      would grow by 2,748,000 (cost-benefit analysis). These figures rise sharply when
      20% of treatments with brand name CBZ are replaced by generic formulations.
      CONCLUSIONS: The bioequivalence ranges authorised for generic formulations may be
      inappropriate for generic AED. With certain AED, replacing a brand name product
      with a generic version of the same medication can have negative effects on the
      amount of health care resources that are consumed and, therefore, on the overall
      economic expenditure associated with epilepsy.

PMID- 15999332
TI  - [Spontaneous bilateral hypertensive haemorrhage of the basal ganglia. Something
      more than Charcot-Bouchard aneurysms?].

PMID- 15999333
TI  - [Acute dystonia following a wasp sting].

PMID- 15999334
TI  - [Yawning and temporal lobe epilepsy].

PMID- 15999335
TI  - Toward direct determination of conformations of protein building units from
      multidimensional NMR experiments VI: chemical shift analysis of his to gain 3D
      structure and protonation state information.
AB  - NMR--chemical shift structure correlations were investigated by using GIAO
      RB3LYP/6-311++G(2d,2p) formalism. Geometries and chemical shifts (CSI values) of
      103 different conformers of N'-formyl-L-histidinamide were determined including
      both neutral and charged protonation forms. Correlations between amino acid
      torsional angle values and chemical shifts were investigated for the first time
      for an aromatic and polar amino acid residue whose side chain may carry different
      charges. Linear correlation coefficients of a significant level were determined
      between chemical shifts and dihedral angles for CSI[(1)H(alpha)]/phi,
      CSI[(13)C(alpha)]/phi, and CSI[(13)C(alpha)]/psi. Protonation of the imidazole
      ring induces the upfield shift of CSI[(13)C(alpha)] for positively charged
      histidines and an opposite effect for the negative residue. We investigated the
      correspondence of theoretical and experimental (13)C(alpha), (13)C(beta), and
      (1)H(alpha) chemical shifts and the nine basic conformational building units
      characteristic for proteins. These three chemical shift values allow the
      identification of conformational building units at 80% accuracy. These results
      enable the prediction of additional regular secondary structural elements (e.g.,
      polyProlineII, inverse gamma-turns) and loops beyond the assignment of chemical
      shifts to alpha-helices and beta-pleated sheets. Moreover, the location of the
      His residue can be further specified in a beta-sheet. It is possible to determine
      whether the appropriate residue is located at the middle or in a first/last beta
      strand within a beta-sheet based on calculated CSI values. Thus, the attractive
      idea of establishing local residue specific backbone folding parameters in
      peptides and proteins by employing chemical shift information (e.g., (1)H(alpha)
      and (13)C(alpha)) obtained from selected heteronuclear correlation NMR
      experiments (e.g., 2D-HSQC) is reinforced.

PMID- 15999337
TI  - Validated HPLC method for the determination of fluconazole in human plasma.
AB  - A high-performance liquid chromatographic assay with UV detection was developed
      for the determination of fluconazole in human plasma. The method utilized solid
      phase extraction for sample clean-up. The separation was performed on a C18
      column by isocratic elution with a mobile phase of 10 mM acetate buffer at pH 5.0
      and methanol and UV detection at 210 nm. Validation was performed according to
      the current recommendations of the USFDA bioanalytical method validation
      guidance. The method proved to be specific, accurate, precise and linear between
      200 and 10,000 ng/mL with correlation coefficients greater than 0.999. The
      coefficient of variation was within 11% and relative deviation was less than 10%.

PMID- 15999338
TI  - Nobiletin: efficient and large quantity isolation from orange peel extract.
AB  - It is known that nobiletin possesses anticancer, antiviral and anti-inflammatory
      activities. Recently, the demand for nobiletin in large quantities and high
      purity has increased. However, conventional normal-phase silica gel
      chromatography and C(18)-reverse-phase separation methods cannot satisfy the
      requirement of pure and gram scale nobiletin in a timely manner. In exploring the
      composition and the biological activities of polymethoxyflavones from sweet
      orange (Citrus sinensis) peel, we developed an efficient isolation method for
      nobiletin. By employing this methodology, pure nobiletin, in gram quantities, was
      obtained in only one purification cycle. The orange peel extract was loaded onto
      a silica gel flash column and eluted by a mixed solvent system of ethyl acetate
      and hexanes, and the fractions collected. Upon combination of the eluted
      fractions, mainly containing nobiletin and 5,6,7,4'-tetramethoxyflavone, and
      concentration under reduced pressure, the resultant residue was loaded onto a
      Regis chiral column. Gram amounts of nobiletin and 5,6,7,4'-tetramethoxyflavone
      were then eluted with ethanol and hexanes, respectively.

PMID- 15999339
TI  - Insecticidal and fungicidal activity of new synthesized chitosan derivatives.
AB  - Chitosan, the N-deacetylated derivative of chitin, is a potential
      biopolysaccharide owing to its specific structure and properties. In this paper,
      we report on the synthesis of 24 new chitosan derivatives, N-alkyl chitosans
      (NAC) and N-benzyl chitosans (NBC), that are soluble in dilute aqueous acetic
      acid. The different derivatives were synthesized by reductive amination and
      analyzed by 1H NMR spectroscopy. A high degree of substitution (DS) was obtained
      with N-(butyl)chitosan (DS 0.36) at a 1:1 mole ratio for NAC derivatives and N
      (2,4-dichlorobenzyl)chitosan (DS 0.52) for NBC derivatives. Their insecticidal
      and fungicidal activities were tested against larvae of the cotton leafworm
      Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae), the grey mould
      Botrytis cinerea Pers (Leotiales: Sclerotiniaceae) and the rice leaf blast
      Pyricularia grisea Cavara (Teleomorph: Magnaporthe grisea (Hebert) Barr). The
      oral feeding bioassay indicated that all the derivatives had significant
      insecticidal activity at 5 g kg(-1) in artificial diet. The most active was N-(2
      chloro-6-fluorobenzyl)chitosan, which caused 100% mortality at 0.625 g kg(-1),
      with an estimated LC50 of 0.32 g kg(-1). Treated larvae ceased feeding after 2-3
      days; the mechanism of action remains unknown. In a radial hyphal growth bioassay
      with both plant pathogens, all derivatives showed a higher fungicidal action than
      chitosan. N-Dodecylchitosan, N-(p-isopropylbenzyl)chitosan and N-(2,6
      dichlorobenzyl)chitosan were the most active against B cinerea, with EC50 values
      of 0.57, 0.57 and 0.52 g litre(-1), respectively. Against P grisea, N-(m
      nitrobenzyl)chitosan was the most active, with 77% inhibition at 5 g litre(-1).
      The effect of different substitutions is discussed in relation to insecticidal
      and fungicidal activity.

PMID- 15999341
TI  - Early postnatal stress alters the 5-HTergic modulation to emotional stress at
      postadolescent periods of rats.
AB  - Several lines of evidence have shown that traumatic events during the early
      postnatal stage might precipitate long-lasting alteration in the functional
      properties underlying emotional expression. The aim of the present study was to
      examine whether the early postnatal stress alters the 5-HTergic mechanism
      underlying regulation of emotional stress, focusing on the 5-HT(1A) receptor
      mediated synaptic responses in adult rats. Pups were exposed to aversive
      stimulus, footshock (FS) at the postnatal period of the second (2W) and the third
      week (3W). At postadolescent period (10-12-week-old), electrophysiological and
      behavioral studies were performed. The 5-HT(1A) receptor agonist tandospirone (10
      mg/kg body wt, i.p.) blocked the long-term potentiation (LTP) in the hippocampal
      CA1 field of 3W-FS, as well as non-FS control, whereas this inhibition was not
      observed in 2W-FS group. Fear-related freezing behavior observed during exposure
      to contextual fear conditioning markedly attenuated in 2W-FS, but not in 3W-FS.
      These data suggest that aversive stress exposed at 2W is attributable to changes
      in the 5-HT(1A) receptor-mediated synaptic plasticity, which may be responsible
      for the attenuation of freezing behavior. Thus, 5-HT(1A) receptors appear to play
      a key role in the 5-HTergic mechanism underlying regulation of emotional stress
      on the postnatal development of the brain. In other words, the second postnatal
      week may be the "critical period" for establishing proper behavioral responses to
      emotional stress in adult rats. (c) 2005 Wiley-Liss, Inc.

PMID- 15999342
TI  - Novelty responses to relational and non-relational information in the hippocampus
      and the parahippocampal region: a comparison based on event-related fMRI.
AB  - We conducted two functional magnetic resonance imaging (fMRI) experiments that
      examined novelty responses in the human medial temporal lobe (MTL) to determine
      whether the hippocampus makes contributions to memory processing that differ from
      those of structures in the adjacent parahippocampal region. In light of proposals
      that such differential contributions may pertain to relational processing
      demands, we assessed event-related fMRI responses in the MTL for novel single
      objects and for novel spatial and non-spatial object relationships; subjects were
      asked to detect these different types of novelties among previously studied
      items, and they successfully performed this task during scanning. A double
      dissociation that emerged from the response pattern of regions in the hippocampus
      and perirhinal cortex provided the strongest support for functional
      specialization in the MTL. A region in the right middle hippocampus responded to
      the novelty of spatial and non-spatial relationships but not to the novelty of
      individual objects. By contrast, a region in right perirhinal cortex, situated in
      the anterior collateral sulcus, responded to the novelty of individual objects
      but not to that of either type of relationship. Other MTL regions that responded
      to novelty in the present study showed no reliable difference in their response
      to the various novelty types; these regions included anterior parts of the
      hippocampus and posterior aspects of parahippocampal cortex. Together, our
      findings indicate that relational processing demands are a critical determinant
      of functional specialization in the human MTL. They also suggest, however, that a
      neuroanatomical framework that only distinguishes between the hippocampus and the
      parahippocampal region is not sufficiently refined to account for all functional
      differences and similarities observed with respect to relational processes in the
      human MTL.

PMID- 15999343
TI  - Cytosolic PLA2 genes possibly contribute to the etiology of schizophrenia.
AB  - The present study detected three single nucleotide polymorphisms (SNPs), BanISNP
      at the PLA2G4A locus, rs1648833 at the PLA2G4B locus, and rs1549637 at the
      PLA2G4C locus, to investigate a genetic association between the cytosolic PLA2
      (cPLA2) genes and schizophrenia. A total of 240 Chinese parent-offspring trios of
      Han descent were recruited for the genetic analysis. The transmission
      disequilibrium test (TDT) showed allelic association for rs1549637 (chi(2) =
      5.68, uncorrected P = 0.017), but not for BanISNP and rs1648833. The conditioning
      on genotype (COG) test revealed a disease association for the BanISNP-rs1648833
      combination (chi(2) = 12.54, df = 3, P = 0.0057) and for the BanISNP-rs1549637
      combination (chi(2) = 9.72, df = 2, P = 0.021), but the conditioning on allele
      (COA) test did not show such an association for the above two combinations.
      Neither the COA test nor the COG showed a disease association for the rs1648833
      rs1549637 combination. In the combination of all three SNPs, the COG test, but
      not the COA test, showed a strong association (chi(2) = 22.93, df = 6, P =
      0.0008). These findings suggest that these three cPLA2 genes may all be involved
      in contributing to the etiology of schizophrenia although their effect size
      appears to be relatively small.

PMID- 15999344
TI  - Association of the promoter polymorphism -1438G/A of the 5-HT2A receptor gene
      with behavioral impulsiveness and serotonin function in women with bulimia
      nervosa.
AB  - Separate lines of research suggest that the functional alterations in the
      serotonin (5-HT) 2A receptor are associated with 5-HT tone, behavioral
      impulsiveness, and bulimia nervosa (BN). We explored the effect of allelic
      variations within the 5-HT2A receptor gene promoter polymorphism -1438G/A on
      trait impulsiveness and serotonin function in women with BN. Participants
      included women with BN having the A allele (i.e., AA homozygotes and AG
      heterozygotes, BNA+, N = 21); women with BN but without the A allele (i.e., GG
      homozygotes, BNGG, N = 12), and normal eater control women having the A allele
      (NEA+, N = 19) or without the A allele (NEGG; N = 9). The women were assessed for
      psychopathological tendencies and eating disorder symptoms, and provided blood
      samples for measurement of serial prolactin responses following oral
      administration of the post-synaptic partial 5-HT agonist meta
      chlorophenylpiperazine (m-CPP). The BNGG group had higher scores than the other
      groups on self-report measures of non-planning and overall impulsiveness and had
      blunted prolactin response following m-CPP. The bulimic groups did not differ
      from each other on current eating symptoms or on frequencies of other Axis I
      mental disorders. Findings indicate that women with BN who are GG homozygotes on
      the -1438G/A promoter polymorphism are characterized by increased impulsiveness
      and lower sensitivity to post-synaptic serotonin activation. These findings
      implicate the GG genotype in the co-aggregation of impulsive behaviors and
      alterations of post-synaptic 5-HT functioning in women with BN.

PMID- 15999345
TI  - Association study of CREB1 and childhood-onset mood disorders.
AB  - Several lines of evidence suggest that the cellular pathways involved in synaptic
      plasticity contribute to the risk of depression. These findings include the
      evidence that chronic antidepressant treatment upregulates the cAMP signal
      transduction cascade resulting in increased expression and function of the cAMP
      responsive element binding protein (CREB), a transcription factor that increases
      the expression of key growth factors involved in synaptogenesis and neurogenesis.
      Recently, linkage to CREB1 was reported for early-onset depression in families
      recruited from the Pittsburgh area. This finding was significant only in female
      sibling pairs from those families. Two specific DNA variants, -656G/A and a C
      insertion/deletion in intron 8, were identified in CREB1 that co-segregated with
      depression in two of the families. We sought to investigate the relationship of
      CREB1 to childhood-onset mood disorders (COMD) using a sample of 195 nuclear
      families (225 affected children) collected in Hungary. We genotyped the two CREB1
      DNA variants previously identified as linked to depression as well as three
      additional polymorphisms spanning the gene. In addition, we genotyped the -656G/A
      DNA change and the intron 8 polymorphism in a sample of 112 probands with mood
      disorders collected in the Pittsburgh area and matched controls, and examined the
      distribution of alleles. The -656A allele was not observed in our samples and
      there was no evidence for association of the intron 8 polymorphism in either the
      sample from Pittsburgh (chi(2) = 0.061, 1 d.f., P = 0.803) or Hungary (chi(2) =
      0.040, 1 d.f., P = 0.842). We found no evidence for an association with the other
      three polymorphisms or with the haplotypes of these markers. Further, we found no
      sex-specific relationship. Our results, therefore, do not support the previous
      evidence for this gene as a major factor contributing to depression.

PMID- 15999346
TI  - Editorial: perspectives on craniosynostosis.

PMID- 15999347
TI  - Multidetector row computed tomography for diagnosing intraductal extension of
      breast carcinoma.
AB  - OBJECTIVES: Several reports supported the association of higher ipsilateral
      breast tumor recurrence rates with positive or intermediate margins compared with
      negative pathologic margins. Precise evaluation of intraductal component and
      adequate surgical margin are important factors affecting the tumor recurrence
      after breast conserving surgery. Numerous studies have reported the utility of
      magnetic resonance imaging for diagnosing developing intraductal extension of
      breast cancer, but few have investigated multidetector-row computed tomography
      (MD-CT). The present study evaluated the clinical utility of MD-CT for detecting
      intraductal extension of breast carcinoma, and analyzed clinical parameters
      affecting the detection of intraductal extension under MD-CT. METHODS: Subjects
      comprised 44 patients grouped into three categories according to degree of
      intraductal extension of the main tumor under MD-CT (Intraductal spread grade 1
      approximately 3: IDS 1 approximately 3). Tumors were also categorized
      histopathologically (p-IDS 0 approximately 3), and CT-pathological correlations
      were examined retrospectively. Clinical parameters were evaluated to determine
      the affect on detection of intraductal components. RESULTS: MD-CT detected 44
      breast lesions (100%). Sensitivity for detection of intraductal component was
      81.2%, specificity was 67.8%, and accuracy was 72.7%. Regarding extent of
      intraductal components, significant correlations were found between
      histopathological and MD-CT findings. A strong correlation was found in
      postmenopausal women between T2 tumor and high histological grade. CONCLUSIONS:
      MD-CT findings of intraductal extension from breast carcinoma correlate with
      histological degree of intraductal extension, and MD-CT may be useful for
      preoperative assessment of breast-conserving surgery, particularly for
      postmenopausal women with histological high nuclear grade and T2 tumor.

PMID- 15999348
TI  - Malignant peritoneal mesothelioma.
AB  - BACKGROUND AND OBJECTIVES: The incidence of malignant peritoneal mesothelioma
      (MPM) is rising. Our aim was to present our experience with this entity in order
      to increase the awareness about this disease to avoid misdiagnosis. METHODS:
      Records of seven patients with histologically confirmed MPM were retrospectively
      reviewed. Demographic and clinicopathological findings were studied in detail.
      RESULTS: There were two females and 5 males; mean age was 50.3 years (range 16
      73). Asbestos exposure was recorded in two patients, familial Mediterranean fever
      in one and previous radiation in one. Main presentations were abdominal pain and
      distension. None of the patients was diagnosed preoperatively. The average delay
      in diagnosis was 10 months. Calretinin expression was identified in all tumors.
      Three patients were treated with cytoreductive surgery combined with systemic
      chemotherapy. Two patients who remain alive were young female patients who were
      diagnosed by laparoscopic incidental findings and were treated with cytoreductive
      surgery combined with hyperthermic intraoperative intraperitoneal chemotherapy
      (HIIC). Median survival was 19.7 months. The average survival time of the five
      patients who died of their diseases was 10.2 months. CONCLUSIONS: An awareness of
      MPM is important to prevent misdiagnosis. Immunohistochemistry has an important
      role in confirming the diagnosis. MPM remains a difficult therapeutic challenge.
      Thorough cytoreductive surgery is the cornerstone of current treatment while HIIC
      is a promising strategy in suitable patients.

PMID- 15999349
TI  - Comparisons of outcomes and survivals for two central venous access port systems.
AB  - BACKGROUND: This study compares the outcomes and survivals between two central
      venous access port systems. STUDY DESIGN: Medical records from 298 cancer
      patients who had received open-end (Deltec, N = 159) or closed-end (Groshong, N =
      139) port catheter insertions were retrospectively reviewed. METHODS: The
      infection, thrombosis, and surgical complication rates (chi-square test), as well
      as mean catheter-indwelling-days (t-test) were compared. Kaplan Meier analysis
      and stratified log rank test were used to compare actuarial survival rates. Cox
      proportion hazard model was applied to analyze the outcomes predictors. RESULTS:
      The total catheter-indwelling-day was 116,603 days in general for this cohort.
      The Groshong catheters (569 +/- 386.1 days) had longer (P < 0.001) mean catheter
      indwelling-day than did Deltec catheters (239 +/- 235.6 days). But the per 1,000
      catheter day infection (Deltec 0.18, Groshong 0.16), thrombosis (Deltec 0.07,
      Groshong 0.06), and surgical complication rates (Deltec 0.07, Groshong 0.02) were
      equivalent (P > 0.05) between two groups. Patients with leukemia were at higher
      risk (odds ratio 13.4, P = 0.009) to develop adverse events. However, two types
      of catheters had similar actuarial survival rates at end of follow up (P > 0.05).
      CONCLUSION: We found infection, thrombosis occlusion, surgical complication, and
      actuarial device survival rates were similar between Deltec and Groshong groups.
      Hematogenous malignancy was a risk factor for catheter failure.

PMID- 15999350
TI  - Recurrent ovarian carcinoma of low malignant potential: the role of secondary
      surgical cytoreduction and the prognosis in Chinese patients.
AB  - BACKGROUND AND OBJECTIVES: The study of pathology and prognosis for patients with
      ovarian tumors of low malignant potential (LMP) has been well documented. The
      treatment, particularly the secondary surgery, for recurrent disease is less
      documented. This study was conducted to investigate the role of secondary
      surgical cytoreduction for recurrent ovarian carcinoma of LMP. METHODS: Patients
      with ovarian carcinoma of LMP at advanced stages experiencing disease recurrence
      and treated by secondary surgical cytoreduction at Fudan University Cancer
      Hospital were retrospectively reviewed. RESULTS: Sixteen patients with recurrent
      serous and mucinous ovarian LMP tumors who underwent secondary surgical
      cytoreduction were entered in this study. The median age was 46.5 years. The 5
      year survival in those with residual disease < or =1 cm after secondary surgical
      cytoreduction was 83%, compared to 26% in those with residual disease >1 cm (P =
      0.01). Multivariate analysis suggested that extent of recurrent disease (solitary
      vs. multiple, relative risk [RR] =2.69, P < 0.01), and residual disease after
      secondary surgical cytoreduction (< or =1 cm vs. >1 cm, RR = 2.56, P < 0.01) were
      determinants of survival. CONCLUSIONS: For recurrent ovarian carcinomas of low
      malignant potential, prolonged survival was observed in patients with solitary
      recurrent disease and optimal secondary surgical outcome.

PMID- 15999351
TI  - The role of glial cell line-derived neurotrophic factor (GDNF) and integrins for
      invasion and metastasis in human pancreatic cancer cells.
AB  - BACKGROUND AND OBJECTIVES: It is generally accepted that the malignancy of
      pancreatic cancer is dependent upon the extent of invasion as well as metastasis.
      However, the factors and mechanisms are incompletely understood. We investigated
      whether glial cell lined-derived neurotrophic factor (GDNF) enhances the invasive
      and adhesive behaviors of pancreatic cancer cells by altering of the expression
      of integrins. METHODS: The expression of the GDNF receptor in pancreatic cancer
      cell lines (SW1990 and Capan-2) was confirmed by RT-PCR. Then we determined the
      expression of integrin subunits and the alteration of their expression by GDNF
      using flow-cytometric analysis and a cellular enzyme-linked immunosorbent assay
      (CELISA). Adhesion and invasion assay were performed to investigate whether
      increased integrin expression affected the interaction between cancer cells and
      ECM proteins. RESULTS: The GDNF receptor subunits were expressed in pancreatic
      cancer cells. GDNF enhanced the expression of some of the integrin subunits and
      increased their adhesive and invasive abilities. The enhanced expression and
      associated increase in adhesive and invasive abilities were inhibited by blocking
      the GDNF receptor or the integrin beta1 subunit. CONCLUSION: The enhancement of
      integrin expression by GDNF signaling through the GDNF receptor strongly
      influences invasion and adhesion to ECM proteins by pancreatic cancer cells.

PMID- 15999352
TI  - Comparison of laparoscopy-assisted by conventional open distal gastrectomy and
      extraperigastric lymph node dissection in early gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopy-assisted gastrectomy with lymph node
      dissection for gastric cancer is considered technically more complicated than the
      open method. Moreover, the safety and efficacy of laparoscopy-assisted distal
      gastrectomy (LADG) with extraperigastric lymph node dissection in patients with
      gastric cancer have not been established yet. To evaluate short-term surgical
      validity, surgical outcome of the laparoscopy-assisted distal gastrectomy (LADG)
      with extraperigastric lymph node dissection was compared with that of the
      conventional open distal gastrectomy (CODG) in patients with early gastric
      cancer. METHODS: One hundred and forty-seven patients with early gastric cancer
      received radical distal gastrectomy during 2002 and 2003, where LADG was
      undergone in 71 patients. The clinicopathologic characteristics, postoperative
      outcomes and courses, and postoperative morbidities and mortalities were compared
      between the two groups. Data were retrieved from the stomach cancer database at
      Dong-A University Medical center. RESULTS: Baseline characteristics, including
      sex, age, body mass index (BMI), American Society of Anesthesiology (ASA) class,
      tumor size, T stage, and lymph node metastasis were similar between the two
      groups. No significant differences were found between these groups in terms of
      the number of retrieved lymph nodes with respect to D1 + alpha (D1 + no. 7) and
      D1 + beta (D1 + no. 7, 8a, and 9) lymphadenectomy. In the LADG group, wound size
      was smaller (P < 0.0001), but operation time was longer (P = 0.0001) than in the
      CODG group. Perioperative recovery was faster in the LADG group than in the CODG
      group, as reflected by a shorter hospital stay (P = 0.0176) and less times of
      additional analgesics (P = 0.0370). Serum albumin level in LADG was higher (P =
      0.0002) on day 7 than that in CODG, and the leukocyte count in LADG lower (P =
      0.0445) on day 1 than that in CODG. Postoperative morbidities and mortalities
      were not significantly different between the two groups. CONCLUSIONS: Our data
      confirmed that LADG with extraperigastric (no. 7, 8, and 9) lymph node dissection
      proved to be feasible and acceptable surgical technique for early gastric cancer.
      At least taking a surgical point of view, LADG with extraperigastric lymph node
      dissection is suggested to be a preferred surgical option for patients with early
      gastric cancer. Its oncologic validity awaits larger and prospective multicenter
      trials.

PMID- 15999353
TI  - Retroperitoneal sarcoma: 25 years of experience with aggressive surgical
      treatment at the Institute of Oncology, Ljubljana.
AB  - BACKGROUND AND OBJECTIVES: Retroperitoneal sarcomas are rare malignant tumors
      with an aggressive course of disease and high local recurrence rate. Local
      disease is the main cause of death. A retrospective study was undertaken to
      evaluate the results of aggressive surgical treatment in a series of patients of
      primary and recurrent retroperitoneal sarcomas. PATIENTS AND METHODS: From 1975
      to 2000, 155 patients with retroperitoneal tumors were operated on at the
      Institute of Oncology, Ljubljana. Patients with fibromatosis and children less
      than 16 years were excluded from further calculation. Out of the rest 139
      patients, 102 patients had localized retroperitoneal sarcoma, and 37 patients had
      retroperitoneal sarcoma with distant metastases Leiomyosarcoma was the most
      common type of histology, followed by liposarcoma and schwannoma. Their referral
      status was as follow: 56 had primary sarcoma, 20 residual sarcoma after operation
      elsewhere and 26 already recurrent sarcoma. Our treatment approach was
      aggressive. We removed surgically primary tumor, recurrent sarcoma and
      metastases, whenever possible. To this end, we performed, 235 operations for
      retroperitoneal sarcomas on 139 patients (up to 8 operations on 1 patient).
      RESULTS: Complete resection was done in 97 of 102 patients with localized sarcoma
      (resectability rate 95%); in 55 patients, R0 resection was made, in 42 patients,
      R1 resection, in 3 patients, debulking procedure, and in 2 patients biopsy alone.
      In 118, patients at least one organ was resected completely or partially en bloc
      with tumor. The 5-, 10-, and 15-year survivals of patients with localized sarcoma
      were 52%, 36%, and 22%, respectively. The 5-year survival of patients with
      metastases was 12% (P = 0.0002), the 5- and 10-year survival rates of patients
      with R0 resection were 75% and 64%, respectively, and of those with R1 resection,
      25% and 8%, respectively (0 < 0.00001). High tumor grade was associated with poor
      survival. The 5-year local recurrence rate of patients with primary sarcoma and
      of those with locally recurrent sarcoma was 37% and 71%, respectively (P = 0.04).
      After the first local recurrence, the 5- and 10-year survival rates were 42% and
      26%, after the second local recurrence 45% and 22%, after the third local
      recurrence 43% and 11%, and after the fourth local recurrence 51% and 17%,
      respectively. CONCLUSION: Complete surgical resection without microscopic
      residuum and contamination is likely to offer the best chances for long-term
      survival. Until there are no other treatment modalities, aggressive surgery for
      recurrent sarcoma is recommended.

PMID- 15999354
TI  - Predictive value of p53 and 14-3-3sigma for the effect of chemoradiation therapy
      on esophageal squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The p53 family regulates cell-cycle arrest, triggers
      apoptosis, repairs DNA damage caused by various genotoxic stresses, and protects
      cells from death upon irradiation. The purpose of the present study was to
      examine the expressions of p53 and one of the p53 family proteins, 14-3-3sigma,
      in biopsy specimens and to predict the clinical and histological responses to
      chemoradiation therapy (CRT) in patients with esophageal squamous cell carcinoma
      (ESCC). METHODS: We investigated with the relationship between p53 and 14-3
      3sigma expressions in biopsy specimens obtained from 62 patients with ESCC and
      analyzed these patients' clinical and histological responses to CRT.
      Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of
      radiation. RESULTS: Following CRT, 71.0% of patients showed a positive clinical
      response and 52.8% showed a positive histological response. The rate of positive
      expression was 43.5% for p53 and 58.1% for 14-3-3sigma. Statistically significant
      correlations were found between p53 expression and clinical response to CRT (P =
      0.001) and histological response to CRT (P = 0.041), and between 14-3-3sigma
      expression and histological response to CRT (P = 0.01). Furthermore, in p53
      positive tumors, CRT was more effective in tumors with 14-3-3sigma-positive
      expressions than those with 14-3-3sigma-negative expressions (P = 0.037). The
      survival rate of the patients with 14-3-3sigma-positive tumors was better than
      those with 14-3-3sigma-negative tumors in patients with p53-positive tumors (P =
      0.047). CONCLUSIONS: We demonstrated that p53-negative or 14-3-3sigma-positive
      expressions were closely related to the response to CRT. It is clinically useful
      to examine the expression of these genes in biopsy specimens for predicting the
      CRT outcomes in patients with ESCC.

PMID- 15999355
TI  - Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection: a
      phase II study following the learning curve.
AB  - BACKGROUND AND OBJECTIVES: A preliminary study on the use of laparoscopy-assisted
      approach to treat gastric carcinoma resulted in higher morbidity. STUDY DESIGN: A
      prospective phase II study of laparoscopy-assisted distal gastrectomy (LADG) was
      performed for patients with preoperative diagnosis of T1 N0 stage cancer located
      in the lower or middle-third stomach. Bleeding amount, operating time, mortality,
      morbidity, and the number of lymph node retrieval were recorded and compared with
      the preliminary series reported previously by the same authors. RESULTS: Between
      2000 and 2002, 47 patients were accrued. The mean blood loss and postoperative
      hospital stay were significantly decreased compared with the previous series,
      whereas the operating time was not. There were no in-hospital deaths, with the
      incidence of anastomotic leakage significantly decreased. All patients remain
      disease-free to date. CONCLUSIONS: LADG can be performed safely and morbidity, no
      longer, is a drawback by experienced hands that have reached plateau of the
      learning curve, although it remains a time-consuming procedure. Its application
      to gastric cancer surgery is feasible for early stage cancer, and its
      applicability to the treatment of T2 stage cancer will be the next issue to be
      explored.

PMID- 15999356
TI  - Value of CT criteria in predicting survival in patients with potentially
      resectable pancreatic head carcinoma.
AB  - BACKGROUND AND OBJECTIVE: Survival is often poor after resection of pancreatic
      tumors. We correlated the pre-operative CTs with survival to find criteria that
      have prognostic value. To establish the prognostic value of CT in patients with
      potentially resectable pancreatic head carcinoma. METHODS: In 71 consecutive
      patients with potentially resectable pancreatic head carcinoma, prognostic
      factors on CT were scored, for example, tumor size, peripancreatic infiltration,
      grades of vascular encasement, and local irresectability. All patients underwent
      surgical exploration. CT findings were compared with results of surgery and
      histopathology. Prognostic factors for resected and unresected tumors were
      analyzed using single and multivariate analysis. RESULTS: Forty-one of 71 tumors
      were resected (24 radical). The sensitivity, specificity, and positive predictive
      value of CT for surgical irresectability were 0.67, 0.63, and 0.57, respectively.
      For a non-radical resection, these were 0.62, 0.75, and 0.83, respectively. The
      median survival was 21 months for resectable tumors and 9.7 months for
      unresectable tumors. For resected tumors, a tumor diameter of > 3 cm (relative
      hazard 3.8) and CT signs of local unresectability showed a poor survival. The
      median survival of resected tumors <2 cm was nearly 30 months. CONCLUSION: CT
      signs of local irresectability and a tumor diameter of >3 cm predict a poor
      survival after resection.

PMID- 15999357
TI  - Univariate and multivariate analysis of prognostic significance of betel quid
      chewing in squamous cell carcinoma of buccal mucosa in Taiwan.
AB  - BACKGROUND AND OBJECTIVES: While betel quid (BQ) chewing is clearly the most
      avoidable risk factor of squamous cell carcinoma of buccal mucosa (BMSCC), little
      is known about the influence of this habit on the prognosis of BMSCC. METHODS: We
      surveyed 280 patients with BMSCC who were treated during an 8-year period in a
      cohort study to assess the independent predictive value of pretreatment BQ
      chewing habit on the prognosis by univariate and multivariate analysis. RESULTS:
      We found by univariate analysis that sex, age, clinical stage, smoking, and BQ
      chewing significantly affected the patients' prognosis and only age, clinical
      stage, and BQ chewing had significant influence on prognosis by multivariate
      analysis (P < 0.05). Further analysis revealed that the prognostic effect of BQ
      chewing changed in a dose- and time-dependent manner. The risk of death was 31.4
      fold higher in heavy user (duration >30 years, daily consumption >30 quids, age
      of start <20 years old) when compared to those who chewed BQ to a milder degree
      (duration <10 years, daily consumption <15 quids, age of start > or =20 years old
      ) (P < 0.001). CONCLUSIONS: Pretreatment BQ chewing habit worsens the prognosis
      of BMSCC in Taiwan. BQ chewing is a prognostic indicator that can be used in
      conjunction with clinical staging to help plan the treatment for the patients.

PMID- 15999358
TI  - Head and neck squamous cell carcinoma: the role of post-operative adjuvant
      radiotherapy.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the leading
      cancers in India. Since a large majority present in loco-regionally advanced
      stages, surgery followed by adjuvant post-operative radiotherapy (PORT) has been
      the mainstay of treatment for resectable HNSCC. AIM: To identify clinico
      pathologic factors that could have an impact on outcome in HNSCC in the
      postoperative setting. MATERIALS AND METHODS: A retrospective review of 348
      previously untreated patients with HNSCC who received PORT following curative
      surgery. The outcome measures were local control, loco-regional control, and
      disease free survival (DFS). RESULTS: With a median follow-up of 36 months
      (range: 2-127 months) for surviving patients, the 5-year local control, loco
      regional control, and DFS was 79%, 63%, and 56%, respectively for all patients.
      On univariate analysis, site of primary was an independent prognostic factor for
      all the outcome measures (P = 0.005, 0.02, and 0.04, respectively) with oral
      cavity lesions faring the worst. Peri-nodal extension (PNE) affected loco
      regional control (P = 0.002) and DFS (P = 0.0005), but was not predictive for
      local control (P = 0.9852). Cut margin positivity predicted for inferior local
      control alone (P = 0.03), the significance of which was lost on multivariate
      analysis. Cox regression analysis however confirmed the significance of primary
      site and PNE as independent prognostic factors. CONCLUSION: Primary site and PNE
      are independent factors predicting outcome in the postoperative radiotherapeutic
      management of HNSCC.

PMID- 15999359
TI  - Preoperative diagnosis of medullary thyroid carcinoma: fine needle aspiration
      cytology as compared with serum calcitonin measurement.
AB  - BACKGROUND AND OBJECTIVES: Preoperative diagnosis of sporadic medullary thyroid
      carcinoma (MTC) has mainly relied on fine needle aspiration cytology (FNAC). The
      present study aimed to compare the sensitivity of this technique with serum
      calcitonin (CT) measurement and to assess the therapeutic implications of an
      inadequate preoperative diagnosis. METHODS: We reviewed the clinical records of
      91 MTC patients treated and/or followed at our institution between January 1990
      and December 2003. RESULTS: After revision of clinical records, 77 individuals
      were considered eligible for the study. FNAC was performed in 67 patients (87%)
      with a sensitivity of 63%; serum CT was measured in 56 patients (73%) with a
      sensitivity of 98%. Both FNAC and serum CT were assessed in 51 patients (66%).
      FNAC detected only 74.5% of MTCs suspected by elevated serum CT. Among patients
      with a cytological diagnosis of MTC, total thyroidectomy (TT) was performed in
      95% of patients. Among patients without a cytological diagnosis of MTC, TT was
      performed in 83% of patients in whom serum CT was evaluated prior to surgery
      whereas it was performed in only 46% of patients in whom CT evaluation was
      lacking. CONCLUSIONS: Despite the higher sensitivity of serum CT measurement, as
      compared with FNAC to diagnose MTC (98% vs. 63%), only 9% of patients might have
      escaped to surgery based on FNAC results. However, indication for surgery based
      on suspicious FNAC may not alert the surgeon for the need of a TT and exploration
      of nodes at least in the central compartment.

PMID- 15999360
TI  - Inguinal canal as an anatomic sanctuary site of relapse in peritoneal
      carcinomatosis previously treated with intraperitoneal chemotherapy.
AB  - Early postoperative intraperitoneal chemotherapy (EPIC) and intraoperative
      peritoneal hypertermic chemotherapy (IPHC) are used in addition with
      cytoreductive surgery to treat with curative intent peritoneal carcinomatosis
      arising from colorectal adenocarcinomas. Three patients with such a disease were
      treated with perioperative intraperitoneal chemotherapy in addition to
      cytoreductive surgery and presented isolated local recurrence located in the
      inguinal canal (round ligament in two and spermatic cord in one). All these
      patients were treated by local surgical excision. No patient showed evidence of
      intra-abdominal recurrence at the last follow-up, but one developed pulmonary
      metastasis. When communicating with the peritoneal cavity, the inguinal canal may
      act as a sanctuary site for peritoneal carcinomatosis, since it is not totally
      soaked by the intraperitoneal chemotherapy solution. A local recurrence is thus
      possible. New clinical presentations such as this one have first to be described
      in order to improve patient follow-up.

PMID- 15999361
TI  - Combined use of imaging and cytologic grading schemes for screen-detected breast
      abnormalities improves overall diagnostic accuracy.
AB  - BACKGROUND: Numeric grading systems have been validated for the reporting of
      mammographic abnormalities and for breast cytology. The impact of integrating
      lesion grades from both disciplines on the accuracy of assessment of screen
      detected lesions has not been investigated. METHODS: In the current study, all
      lesions were prospectively classified using the Tabar radiologic grading system,
      as well as the National Health Service Breast Screening Programme (NHSBSP)
      cytologic reporting system. For lesions assessed between January 1996 and January
      2003, based on final histology or 12 months of follow-up, positive predictive
      values (PPV) were calculated for each imaging grade and for each cytologic
      grouping. After integration of the data, changes in the PPV and the negative
      predictive values (NPV) of cytology among lesions with varying imaging grades
      were tracked. RESULTS: Data were retrieved for 4806 lesions. The differences in
      the rates of malignancy for lesions in the different imaging grades were
      significant (Grade 5, 95.8%; Grade 4, 54.6%; Grade 3, 11.6%) (P < 0.001).
      Similarly, the cytologic categories stratified lesions into groups with
      significantly different rates of malignancy (positive, 99.5%; suspicious, 89.2%;
      atypical, 43.4%; benign, 5.7%; inadequate, 33.3%) (P < 0.001). Integration of
      cytologic results with the imaging grade of lesions led to significant
      improvements in the PPV and NPV. Positive smears were likely to represent
      malignant lesions in 99.9% of Grade 5 lesions, 99.2% of Grade 4 lesions, and
      95.2% of Grade 3 lesions (P < 0.0001). Similarly, negative cytology corresponded
      to a nonmalignant lesion in 99% of Grade 3 lesions, 81.6% of Grade 4 lesions, and
      in only 45.5% of Grade 5 lesions (P < 0.001). CONCLUSIONS: The integration of
      numeric grading schemes for breast imaging and cytology improves the accuracy of
      assessment of screen-detected lesions. Because 99.9% of Grade 5 lesions with
      positive cytology are malignant, core biopsy confirmation may not be required in
      this group.

PMID- 15999363
TI  - Treatment of nasopharyngeal carcinoma in children and adolescents: definitive
      results of a multicenter study (NPC-91-GPOH).
AB  - BACKGROUND: Preliminary results of combined neoadjuvant chemotherapy,
      radiotherapy, and postradiation interferon beta (IFN-beta) in children and
      adolescents with nasopharyngeal carcinoma, especially in high-risk patients, have
      been promising. METHODS: From 1992 to 2003, 59 patients (58 high-risk patients
      and 1 low-risk patient, median age 13 yrs; range, 8-25 yrs) were treated in the
      GPOH-NPC-91 study. The Stage II patient received irradiation as initial therapy.
      Fifty-eight patients received preradiation chemotherapy with methotrexate,
      cisplatin, and 5-fluorouracil. The cumulative radiation dose to primary sites was
      59.4 Gy, a total dose of 45 Gy was delivered to the neck area. After irradiation,
      all patients were treated with 10(5) U recombinant IFN-beta/kg body weight 3
      times a week for 6 months. RESULTS: After combination therapy, complete response
      was accomplished in 58 patients. In one patient, there was tumor progression
      during chemotherapy. In 3 patients, distant metastases were observed 14, 15, and
      18 months after diagnosis, respectively. One patient had a local relapse 12
      months after diagnosis. Fifty-four patients are still in first remission with a
      median follow-up of 48 months (range, 10-110 mos). Chemotherapy-related toxicity
      was mucositis Grade II, III, or IV in all patients and acute cardiotoxicity in 2
      (3.5%) of the patients. Nephrotoxicity Grade I-II occurred in 8.8% of patients.
      CONCLUSIONS: The combination of initial chemotherapy, radiotherapy, and IFN-beta
      results in an excellent outcome. These results strongly support the development
      of a future treatment strategy along this line.

PMID- 15999362
TI  - Amifostine does not protect against the ototoxicity of high-dose cisplatin
      combined with etoposide and bleomycin in pediatric germ-cell tumors: a Children's
      Oncology Group study.
AB  - BACKGROUND: High-dose cisplatin combined with etoposide and bleomycin (HDPEB)
      improves event-free survival (EFS) in advanced pediatric germ-cell tumors (PGCT),
      but has significant ototoxicity. Amifostine appears to protect against toxicity.
      The authors combined amifostine with HDPEB and evaluated the efficacy and
      toxicity, specifically whether ototoxicity decreased. METHODS: Eligibility
      criteria included age < 15 years and unresectable Stage III/IV extracranial,
      extragonadal PGCT. Patients received bleomycin 15 IU/m(2) on Day 1, then
      etoposide 100 mg/m(2) per day, amifostine 825 mg/m(2) per day, and cisplatin 40
      mg/m(2)per day on Days 1-5, intravenously. The cycles were repeated every 3-4
      weeks with imaging evaluation after 4 cycles. Patients with residual radiographic
      abnormalities underwent resection. Patients with residual tumor received two
      additional HDPEB cycles. Hearing evaluations were required at diagnosis and after
      two and four cycles. Audiologic results were reviewed and compared with
      historical controls treated with HDPEB. RESULTS: Twenty-five eligible patients
      were enrolled between April 2000 and April 2002. Their median age was 1.6 years
      (range, 0.64-13.9 years), 17 patients were female, 11 had metastases, and 24 had
      a yolk sac carcinoma component histologically. Primary sites included
      sacrococcygeal area/pelvis (n = 15), vagina (n = 5), and other (n = 5). Two-year
      EFS and overall survival were 83.5% +/- 12.8% and 85.6% +/- 12.3%, respectively.
      Eight patients were removed from the study (four had progressive disease/disease
      recurrence and four had ototoxicity). Grade 3/4 toxicities included neutropenia
      (n = 20), thrombocytopenia (n = 14), electrolyte imbalances (n = 14), and
      gastrointestinal toxicity (n = 12). Twenty-four of 25 patients received hearing
      evaluations, and 75% had significant hearing loss. CONCLUSIONS: Amifostine did
      not protect against HDPEB-associated ototoxicity.

PMID- 15999364
TI  - DNA methyltransferase 1 expression and promoter methylation of E-cadherin in
      mucoepidermoid carcinoma.
AB  - BACKGROUND: Loss of E-cadherin expression is found frequently in many types of
      human malignancies, including mucoepidermoid carcinoma (MEC). CpG methylation in
      the promoter region has proven important in the regulation of gene expression
      implicated in malignant transformation. DNA methyltransferases (DNMTs) are the
      major enzymes involved in establishing genomic methylation patterns. The current
      study was designed to test the hypothesis that CpG methylation of the promoter
      region of the E-cadherin gene may inactivate its expression and to examine DNMT 1
      (DNMT1) protein expression in MEC. METHODS: Genomic DNA was obtained from
      paraffin embedded sections by laser microdissection in 46 MEC specimens.
      Methylation status of the E-cadherin promoter was examined by utilizing the
      methylation-specific polymerase chain reaction assay. To examine E-cadherin and
      DNMT1 proteins expression levels, the MEC specimens and adjacent epithelial
      tissues were studied immunohistochemically. Chi-square analysis was used to
      evaluate the correlation of protein expression and E-cadherin methylation status
      with clinicopathologic parameters. Comparisons of the survival rate between
      patients with DNMT1-positive and DNMT1-negative patients were made using Kaplan
      Meier analysis. RESULTS: The data showed that all normal tissues expressed E
      cadherin, and no promoter methylation was detected. Of the MEC samples analyzed,
      methylation allele was found in 33 of 46 samples (72%), and reduced E-cadherin
      expression was found in 21 of 46 samples (45%). DNMT1-positive expression was
      observed in 29 of 46 MEC samples (63%). A significant correlation was found
      between E-cadherin expression and the methylation status of E-cadherin promoter
      (P = 0.021). In addition, increased DNMT1 expression was correlated with
      histologic grade, clinical stage, and a poor prognosis in patients with MEC.
      CONCLUSIONS: Hypermethylation of CpG sites at the 5' promoter of E-cadherin was a
      common event associated with E-cadherin expression levels in MEC, suggesting an
      epigenetically mediated loss of E-cadherin function in these tumors. Increased
      DNMT1 protein expression may play a critical role in the carcinogenesis and
      disease progression of MEC.

PMID- 15999365
TI  - Safely reducing length of stay after open radical retropubic prostatectomy under
      the guidance of a clinical care pathway.
AB  - BACKGROUND: Collaborative care pathways have proven to be a safe and effective
      method of decreasing length of hospital stay (LOS) and costs after radical
      retropubic prostatectomy (RRP). In the current study, the authors evaluated the
      safety and efficacy of a pathway transitioning from a 3-day to a 2-day LOS.
      METHODS: The authors performed a retrospective chart review of 994 patients who
      underwent RRP at the study institution between July 1994 and December 2001. A
      total of 561 patients were managed on a 3-day LOS pathway, 172 were managed
      during the transition period from 3 to 2 days, and 261 were managed on a 2-day
      LOS pathway. Statistical analysis was performed comparing preoperative variables
      and complications among the three groups. RESULTS: No statistically significant
      differences were found in comparisons of preoperative and demographic variables
      including age, race, medical comorbidities, preoperative prostate-specific
      antigen level, clinical stage of disease at presentation, and biopsy Gleason
      score. Forty-nine of the 561 patients (8.7%) remained longer than their targeted
      3-day LOS, whereas 14 of 261 patients (5.4%) were hospitalized for longer than
      their targeted 2-day LOS, a difference that approached statistical significance
      (P = 0.058). During the transition period, 99 of 172 patients (57.6%) were
      discharged on postoperative Day 2 and 73 patients (42.4%) were discharged on
      postoperative Day 3. Complication rates were found to be significantly lower (P =
      0.013) in the 2-day LOS group (2.3%) compared with the 3-day LOS group (7.0%) and
      the transition group (8.1%). The rate of readmission remained constant at 3%
      during this time period. CONCLUSIONS: Overall, greater than 90% of patients were
      discharged within 2-3 days of surgery with acceptable complication rates,
      suggesting that in a consistent patient population, the transition from a 3-day
      LOS to a 2-day LOS can be done successfully without compromising patient safety.
      Evaluation currently is ongoing with regard to a 1-day LOS.

PMID- 15999366
TI  - Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma
      development in patients with cirrhosis without transcriptional repression of p16.
AB  - BACKGROUND: Inhibitor of differentiation/DNA binding protein 1 (Id-1) plays a
      pivotal role in the regulation of cell proliferation and carcinogenesis via
      inhibiting basic helix-loop-helix (HLH) transcription factors. Recently, Id-1 was
      found to repress p16 in tumorous tissue specimens including hepatocellular
      carcinoma (HCC), but its relevance in precancerous liver tissues is unknown.
      METHODS: Id-1 expression in the liver tissue specimens of 112 patients with
      cirrhosis without HCC was studied by immunohistochemical analysis. Correlations
      were investigated between Id-1 expression and clinicopathologic features, the
      status of p16, and the risk of HCC occurrence. RESULTS: A high expression of Id-1
      was observed in 42 patients (38%). The level of Id-1 expression was not
      associated with clinical standard parameters or the status of p16 in cirrhotic
      tissue specimens. The cumulative incidence of HCC development was significantly
      higher in a group of patients with high Id-1 expression (P = 0.0008).
      Multivariate analysis revealed that increased Id-1 expression is an independent
      significant factor for the risk of HCC development in patients with cirrhosis
      (relative risk = 2.75, P = 0.003). CONCLUSIONS: The results of the current study
      suggested that increased expression of Id-1 may play an important role in the
      early step of hepatocarcinogenesis, and might serve as a useful marker for
      determining patients with cirrhosis with a high risk of HCC occurrence.

PMID- 15999367
TI  - Early growth response gene 1 (EGR1) is deleted in estrogen receptor-negative
      human breast carcinoma.
AB  - BACKGROUND: Patients with estrogen receptor (ER)-positive and ER-negative breast
      carcinomas differ in terms of disease progression, treatment regimens, and
      prognosis. The mechanism underlying the biologic differences of the two groups is
      understood poorly. Array comparative genome hybridization (CGH) on breast
      carcinoma subtypes demonstrated a consistent association between loss in regions
      of chromosome 5q and ER-negative tumors. It was shown previously that early
      growth response gene 1 (EGR1) on 5q acts like a tumor-suppressor gene, with its
      expression repressed in breast carcinomas. METHODS: To test the hypothesis that
      EGR1 is deleted differentially in ER-negative versus ER-positive breast
      carcinomas, fluorescence in situ hybridization was employed in this study to
      determine the EGR1 deletion status in 50 breast carcinoma specimens. Deletion
      status was measured by the signal ratio of EGR1/chromosome 5. Linear regression
      was used to assess the results. RESULTS: The mean EGR1/chromosome 5 ratio for the
      ER-negative group was significantly lower compared with the same ratio for the ER
      positive group (P < 0.001). Although grade alone was not significant for
      predicting the ratio, the interaction between ER status and grade was significant
      (P < 0.01): For ER-negative specimens, the higher the grade, the lower the
      EGR1/chromosome 5 ratio. CONCLUSIONS: The EGR1 gene appeared to be deleted in ER
      negative human breast carcinomas. Egr-1 may contribute to the pathogenesis of ER
      negative breast carcinomas versus ER-positive breast carcinomas.

PMID- 15999369
TI  - The feasibility of neoadjuvant high-dose chemotherapy and autologous peripheral
      blood stem cell transplantation in patients with nonmetastatic high grade
      localized osteosarcoma: results of a phase II study.
AB  - BACKGROUND: The primary and secondary objectives of the current study were to
      improve the > or = 90% tumor necrosis rate and assess the toxicity profile of the
      neoadjuvant high-dose chemotherapy (HDC) regimen, respectively. METHODS: Twenty
      two patients with AJCC Stage IIB high-grade osteosarcoma were included in the
      current study. Two cycles of an induction chemotherapy regimen including
      cisplatin, doxorubicin, and ifosfamide followed by HDC and autologous peripheral
      blood stem cell support or transplantation (APBSCT) were given. After engraftment
      was achieved, the patients underwent limb-sparing surgery (LSS) followed by three
      to six cycles of postoperative chemotherapy depending on the tumor necrosis rate.
      RESULTS: The median follow-up, the total duration of treatment, and the time to
      surgery were 23.7 months, 5.96 months, and 3.03 months, respectively. The
      necrosis rate was at least 90% in 82% of the cases. The 3-year overall survival
      (OS) and disease-free survival (DFS) rates were 83% and 70%, respectively.
      Leukopenia, anemia, thrombocytopenia, nausea and emesis, and mucositis were the
      most frequent Grade 3 and Grade 4 toxicities (according to the National Cancer
      Institute Common Toxicity Criteria [version 2.0]) of induction, high-dose, and
      adjuvant chemotherapies. At the time of last follow-up, no patient had died of
      chemotherapeutic toxicity. LSS was performed in all patients. Surgery-related
      complications were reported in 3 of 22 patients. Functional scoring results were
      excellent in eight patients, good in nine patients, fair in two patients, and
      poor in three patients. CONCLUSIONS: The results of the current Phase II study
      suggest that neoadjuvant HDC provides a greater than 90% necrosis rate with
      acceptable toxicity. A short duration of therapy and the feasibility of LSS in
      all patients are additional advantages of this approach.

PMID- 15999368
TI  - Blastic natural killer cell lymphoma/leukemia (CD56-positive blastic tumor):
      prognostication and categorization according to anatomic sites of involvement.
AB  - BACKGROUND: Blastic natural killer (NK) cell lymphoma/leukemia (BNKL) is an
      immature CD56-positive neoplasm, which was recognized recently and characterized
      by systemic proliferation of tumor cells including skin, lymph node, and bone
      marrow. METHODS: The current study analyzed 47 patients with BNKL (27 had
      leukemias and 20 had lymphomas). Patient data were collected for the survey of
      the NK-Cell Tumor Study Group. RESULTS: There were 33 males and 14 females, with
      a median age of 53 years (range, 3 months to 89 years). There were few
      clinicopathologic differences between the leukemia and lymphoma types. Cutaneous
      involvement was noted at diagnosis in 28 patients, who presented a tendency for
      older age of onset (median: 56 vs. 46 years, P = 0.11) than patients with
      noncutaneous BNKL. Cutaneous BNKL showed less frequent mediastinal involvement
      (4% vs. 53%, P = 0.0002) and less severe thrombocytopenia (P =0 .03). Phenotypic
      characteristics were also different, with cutaneous BNKL favoring CD4 and HLA-DR
      expression, and noncutaneous BNKL favoring CD16 and CD34 expression. Both groups
      responded well to chemotherapy for lymphoid malignancies, but disease recurrence
      was frequent. The prognosis of patients with noncutaneous BNKL was significantly
      poorer than that of patients with cutaneous BNKL (median survival: 15 vs. 25
      months, P = 0.02). Multivariate analysis confirmed that cutaneous involvement was
      a significant and independent prognostic factor for BNKL, as were age of onset
      and leukocyte count. CONCLUSIONS: These findings suggested that BNKL is a
      heterogeneous disease and contains at least two subtypes. Although further
      investigations are needed to settle a marker for distinction, the presence of
      cutaneous involvement is a useful prognostic factor.

PMID- 15999371
TI  - Stable reagents for the generation of N-centered radicals: hydroamination of
      norbornene.

PMID- 15999370
TI  - Total spontaneous resolution of chiral covalent networks from stereochemically
      labile metal complexes.
AB  - Stereochemically labile copper and zinc complexes with the N,N'
      dimethylethylenediamine ligand (dmeda) have been shown to be promising precursors
      for the total spontaneous resolution of chiral covalent networks. (N,N')
      [Cu(NO3)2(dmeda)]infinity crystallises as a conglomerate and yields either
      enantiopure (R,R)-1 or enantiopure (S,S)-1. A mixed-valence copper(I/II) complex,
      [{Cu(II)Br2(dmeda)}3(Cu(I)Br)2]infinity (2), which crystallises as a pair of
      interpenetrating chiral (10,3)-a nets, is formed from CuBr, CuBr2 and dmeda. One
      net contains ligands with solely (R,R) configuration and exhibits helices with
      (P) configuration while the other has solely (S,S)-dmeda ligands and gives rise
      to a net in which the helices have (M) configuration. The whole crystalline
      arrangement is racemic, because the interpenetrating chiral nets are of opposite
      handedness. With zinc chloride (R,S)-[ZnCl(dmeda)2]2[ZnCl4] (3) is obtained,
      which is a network structure, although not chiral. Total spontaneous resolution
      of stereochemically labile metal complexes formed from achiral or racemic
      building blocks is suggested as a viable route for the preparation of covalent
      chiral networks. Once the absolute structure of the compound has been determined
      by X-ray crystallography, a quantitative determination of the enantiomeric excess
      of the bulk product can be undertaken by means of solid-state CD spectroscopy.

PMID- 15999372
TI  - Engineering enhanced protein stability through beta-turn optimization: insights
      for the design of stable peptide beta-hairpin systems.

PMID- 15999373
TI  - Size-dependent optical properties of MgO nanocubes.

PMID- 15999374
TI  - The thermal unfolding of native cytochrome c in the transition from solution to
      gas phase probed by native electron capture dissociation.

PMID- 15999375
TI  - Antimony-tungsten triple bond: a stable complex with a terminal antimony ligand.

PMID- 15999376
TI  - Actinide materials adopt curvature: nanotubules and nanospheres.

PMID- 15999377
TI  - A calix[5]arene-based heterotetratopic host for molecular recognition of long
      chain, ion-paired alpha,omega-alkanediyldiammonium salts.

PMID- 15999378
TI  - An unusual ditelluride: synthesis and molecular and electronic structures of the
      dimer of the tellurium-centered radical [TePiPr2NiPr2PTe].

PMID- 15999379
TI  - Construction of pseudo-heterochiral and homochiral di-mu-oxotitanium(Schiff base)
      dimers and enantioselective epoxidation using aqueous hydrogen peroxide.

PMID- 15999380
TI  - A stable structurally characterized phosphorus-bound isocyanide and its thermal
      and catalyzed isomerization to the corresponding cyanide.

PMID- 15999381
TI  - Ultramacrocyclization through reversible catenation.

PMID- 15999382
TI  - Femtosecond S3-->S1 conversion and structural reorganisation of trans-3
      phenylprop-2-enaldehyde and derivatives in solution.
AB  - Photoinduced excited-state relaxation of trans-3-phenylprop-2-enaldehyde
      (cinnamaldehyde) and three derivatives was studied in hexane and acetonitrile
      with the pump-supercontinuum-probe technique. Transient spectra were measured
      with 50 fs resolution in the range 260-660 nm after S3<--S0 excitation at 288 nm.
      The early spectra reveal an ultrafast, 0.1-0.5 ps, interchange of intensity
      between two excited-state absorption (ESA) bands followed by a approximately 3 ps
      decay of ESA. This behaviour is interpreted with the help of semiempirical
      calculations, which indicate that the sub-picosecond evolution is consistent with
      S3-->S1 excited-state relaxation while the picosecond decay should be due to a
      structural intramolecular rearrangement. The latter may consist of a twist of the
      phenyl ring and rotation around the C==C bond to a perpendicular conformation
      which corresponds to the global energy minimum in the S1 state and serves as
      source for trans and cis isomers in the ground state.

PMID- 15999383
TI  - First insight into the symmetry and flexibility of membrane efflux pump P
      glycoprotein by novel bifunctional modulators.

PMID- 15999384
TI  - Kinetic and DFT studies on the Ag/TiO2-photocatalyzed selective reduction of
      nitrobenzene to aniline.
AB  - TiO2 particles loaded with silver nanoparticles with a mean diameter of 1.5 nm
      exhibit a high photocatalytic activity (84 % conversion after 1 h irradiation)
      for the reduction of nitrobenzene to aniline with 100 % selectivity in the
      presence of CH3OH (concentration=100 mM). High-resolution transmission electron
      microscopic studies of Pt-photodeposited Ag/TiO2 demonstrate that the Ag
      nanoparticles act as reduction sites in the photocatalytic reaction. Both
      spectroscopic measurements and density functional theory (DFT) calculations
      reveal that nitrobenzene is selectively adsorbed onto the Ag surfaces of Ag/TiO2
      via partial electron transfer from Ag to nitrobenzene, whereas the interaction
      between aniline and Ag/TiO2 is weak. The kinetic analysis indicates that the
      recombination between the electrons flowing into the Ag nanoparticle and the
      holes left in the TiO2 valence band is significantly suppressed, particularly in
      the presence of CH3OH. The high activity and selectivity in the present Ag/TiO2
      photocatalyzed reduction are rationalized in terms of the charge separation
      efficiency, the selective adsorption of the reactants on the catalyst surfaces,
      and the restriction of the product readsorption.

PMID- 15999385
TI  - Gas-phase structure of N,N-dimethylglycine.
AB  - Three conformers of the neutral amino acid N,N-dimethylglycine [(CH3)2NCH2COOH]
      were detected in a supersonic expansion by a combination of laser ablation (LA)
      and molecular-beam Fourier transform microwave (MB-FTMW) spectroscopy. A
      bifurcated methyl-to-carbonyl (C--HO==C) weak intramolecular hydrogen bond might
      stabilise the most stable conformer of C(s) symmetry. The second most stable
      conformer of C1 symmetry has a hydrogen bond between the hydroxyl group and the
      lone pair at the nitrogen atom (NH--O). The r(s) and r0 structures were derived
      for this conformer from the rotational data for the parent and six minor 13C, 15N
      and OD isotopomers. A third conformer exhibits a cis-carboxyl functional group
      and C1 symmetry. Ab initio MP2/6-311++G(d,p) predictions of the spectroscopic
      parameters were useful in analysing the spectra. In particular, the agreement of
      the nuclear quadrupole coupling constants with those calculated was conclusive in
      identifying the different conformers.

PMID- 15999386
TI  - Linear configuration of the spins of a stable trinitroxide radical based on a
      ternary helical peptide.

PMID- 15999387
TI  - High-density data recording in an optoelectrical dual-responsive thin film.

PMID- 15999388
TI  - Formation and decomposition of surface ethoxy species on acidic zeolite Y.

PMID- 15999389
TI  - Synthesis of nanoscopic optical fibers using lipid membranes as templates.

PMID- 15999390
TI  - Monomeric thallium(I) complexes of fluorinated triazapentadienyl ligands.

PMID- 15999391
TI  - A concise and general method for doubly attaching 2-ketosugars to aglycon diols:
      synthesis of the gomphosides and spectinomycin.

PMID- 15999392
TI  - Carving the active site of almond R-HNL for increased enantioselectivity.

PMID- 15999396
TI  - Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit
      lung using an intratracheal catheter.
AB  - BACKGROUND: Poor transduction of the ciliated airway epithelium and inefficient
      airway delivery of viral vectors are common difficulties encountered in lung gene
      therapy trials with large animals and humans. METHODS: We delivered a helper
      dependent adenovirus vector, incorporating a human epithelial cell-specific
      expression cassette, to rabbit lung. An intratracheal device was used to
      aerosolize a moderate dose of virus (5 x 10(11) particles), mixed with the
      enhancing agent LPC (L-alpha-lysophosphatidylcholine), directly into the airways.
      Lung mechanics, body weight and temperature, transgene expression and
      histopathology were studied at day 5. RESULTS: Transgene expression was seen in
      the epithelium of large and small airways, from trachea to terminal bronchioles,
      with a strong tendency toward the right lung. All cell types of the surface
      epithelium were transduced. Extensive transduction of the epithelium (66% of
      cells in trachea) was obtained using virus formulated in isotonic 0.1% LPC, while
      virus formulated in 0.01% LPC transduced fewer cells (24% in trachea). A
      transient decrease in dynamic lung compliance was observed immediately following
      aerosol delivery. Fever and mild-to-moderate patchy pneumonia without edema were
      also observed. CONCLUSION: These data demonstrate a strategy for efficient and
      effective transduction of airway epithelium in a large animal.

PMID- 15999397
TI  - In vivo transduction of HIV-1-derived lentiviral particles engineered for
      macrolide-adjustable transgene expression.
AB  - BACKGROUND: The molecular merger of latest-generation transduction technologies
      with advanced transgene control modalities may foster decisive advances in
      therapeutic reprogramming of somatic cell phenotypes. METHODS: We have engineered
      self-inactivating HIV-1-based lentiviral expression vectors for reversible
      macrolide-adjustable transgene expression. RESULTS: Lentiviral particles
      engineered for macrolide-responsive human vascular endothelial growth factor 121
      (VEGF121) expression compared favourably with isogenic streptogramin- and
      tetracycline-responsive configurations and showed excellent growth-factor fine
      tuning following transduction into a variety of mammalian cell lines and
      different human primary cells. Chicken embryos transduced for macrolide
      controlled VEGF121 production exhibited dose-dependent neovascularization and
      exemplified lentivector-delivered transgene transcription fine-tuning in vivo.
      CONCLUSIONS: Macrolide-adjustable lentivectors enable robust and precise in vitro
      and in vivo transgene fine-tuning which may give future gene therapy trials a new
      impetus.

PMID- 15999398
TI  - Human KAP genes, only the half of it? Extensive size polymorphisms in hair
      keratin-associated protein genes.

PMID- 15999399
TI  - Herpes-associated erythema multiforme.

PMID- 15999400
TI  - Prison health: a threat or an opportunity?

PMID- 15999401
TI  - Emergency contraception: prudes and prejudice.

PMID- 15999402
TI  - Meadow fought to make paediatrics a specialty.

PMID- 15999403
TI  - Clinician expert witnesses take the stand.

PMID- 15999404
TI  - UK child protection services under threat.

PMID- 15999405
TI  - Contemporary assessment and management of neuropathic pain.
AB  - Preclinical studies have increased our understanding of the pathophysiology of
      neuropathic pain at the anatomic, cellular, and molecular levels. These lines of
      investigation have enabled more logical uses of older therapies for neuropathic
      pain and have contributed to our understanding of the potential mechanisms
      underlying the efficacy of newer remedies. The identification of receptor systems
      and the development of genetically modified animal models for the study of
      neuropathic pain have greatly increased our understanding of effective clinical
      treatments. This review focuses on the central and peripheral nervous system
      changes believed to be important in the initiation and perpetuation of
      neuropathic pain. Currently used medications, as well as medications that are on
      the horizon, are highlighted.

PMID- 15999406
TI  - [Telemetry-assisted self-tonometry (TAS)].

PMID- 15999408
TI  - Len would qualify for carer's allowance, but if he claims it, he will actually be
      paid it...

PMID- 15999409
TI  - Psychiatry has effectively become a commodity that is being sold to the drug
      industry.

PMID- 15999410
TI  - Diabetes basics. A winning combo. Your health care team.

PMID- 15999411
TI  - Just for teens. Safe at school.

PMID- 15999412
TI  - Healthy eating 101. Don't starve yourself. Trimming, not slashing, calories is
      key to successful long-term weight loss.

PMID- 15999413
TI  - Healthy eating 101. Watch your portions. For weight control and good health, keep
      your eyes on the size.

PMID- 15999414
TI  - Healthy eating 101. Know your fats. Protect your heart by replacing harmful types
      with healthier ones.

PMID- 15999415
TI  - Healthy eating 101. Choose your carbs carefully. When it comes to good health,
      not all carbohydrates are created equal.

PMID- 15999416
TI  - Healthy eating 101. Click your way to healthier eating. The Internet puts
      countless nutrition resources at your fingertips. Here are some of the best.

PMID- 15999417
TI  - Research profile. Vitamins C and E. Protection for your blood vessels? David S.
      Schade, MD.

PMID- 15999418
TI  - Cryo-cooling in macromolecular crystallography: advantages, disadvantages and
      optimization.
AB  - The flash-cooling of crystals in macromolecular crystallography has become
      commonplace. The procedure makes it possible to collect data from much smaller
      specimens than was the case in the past Also, flash-cooled crystals are much less
      prone to radiation damage than their room-temperature counterparts, allowing data
      to be accumulated over extended periods of time. Notwithstanding the
      attractiveness of the technique, it does have potential disadvantages. First,
      better methods need to be developed to prevent damage to crystals on freezing.
      There is also a risk that structures determined at low temperature may suggest
      conclusions based on aspects of the structure that are not necessarily relevant
      at room temperature.

PMID- 15999419
TI  - Computational analysis of membrane proteins: genomic occurrence, structure
      prediction and helix interactions.
AB  - We review recent computational advances in the study of membrane proteins,
      focusing on those that have at least one transmembrane helix. Transmembrane
      protein regions are, in many respects, easier to investigate computationally than
      experimentally, due to the uniformity of their structure and interactions (e.g.
      consisting predominately of nearly parallel helices packed together) on one hand
      and presenting the challenges of solubility on the other. We present the progress
      made on identifying and classifying membrane proteins into families, predicting
      their structure from amino-acid sequence patterns (using many different methods),
      and analyzing their interactions and packing The total result of this work allows
      us for the first time to begin to think about the membrane protein interactome,
      the set of all interactions between distinct transmembrane helices in the lipid
      bilayer.

PMID- 15999420
TI  - The impact of pre-radiotherapy surgery on radiation-induced lung injury.
AB  - AIMS: The use of postoperative radiation therapy (PORT) is predicated by an
      assessment of the potential benefits and risks, including radiation-induced lung
      injury. In this study, the risk of radiation-induced lung injury is assessed in
      patients who received PORT, and compared with a group of patients who received
      radiation without prior surgery, to determine if surgery increases the risk of
      radiation pneumonitis. MATERIALS AND METHODS: From 1991 to 2003, 251 patients
      with lung cancer were enrolled into a prospective study to assess radiation
      induced lung injury. All patients received three-dimensional-planned, external
      beam radiotherapy. One hundred and seventy-seven patients with over 6-months
      follow-up were eligible. For the current analysis, 49 patients (28%) had surgical
      intervention before radiotherapy. The rates of Grade 2 symptomatic pneumonitis in
      subgroups, based on the type of pre-radiation surgery, were computed and compared
      using Fisher's Exact Test. To consider the confounding factor of irradiated lung
      volume, patient subgroups were further defined on the basis of the mean lung
      dose. RESULTS: Surgical procedures included pneumonectomy (n=9), lobectomy
      (n=16), wedge resection (n=8) and exploration without resection (n=16). Radiation
      induced lung injury occurred in 33 out of 177 (19%) patients, including 18% of
      the surgical group and 19% of the non-surgical group. Additionally, no
      statistically significant difference was found in the rate of radiation-induced
      lung injury based on the extent of resection. CONCLUSIONS: The incidence of
      pneumonitis is similar in the surgical and non-surgical groups. Thus, PORT may be
      safely given to selected patients after surgical exploration or resection.

PMID- 15999421
TI  - The clinical application of hyaluronic acid in gingivitis therapy.
AB  - OBJECTIVE: The efficacy of a topical application of hyaluronic acid (HA) was
      tested for treating gingivitis. METHOD AND MATERIALS: Sixty nonsmoking
      outpatients in good general condition, with clinical signs of gingivitis, were
      included in the study. Forty patients (HA group, 20 men, 20 women; age: 32.8 +/-
      11.3 years) used a spray containing HA 5 times daily over a period of 1 week. The
      control group consisted of 20 patients (10 men, 10 women; age: 31.3 +/- 9.3
      years). The clinical parameters DMF-T (decayed, missed, filled teeth) index,
      approximal plaque index, sulcus bleeding index, papilla bleeding index, and
      gingival crevicular fluid were measured at baseline (T1), after 3 days (T2), and
      after 7 days (T3). RESULTS: A reduction in the sulcus bleeding index of the HA
      group (T1: 72.9 +/- 19.5%) to 50.3 +/- 21.1% was noted at T2, and at T3 the
      sulcus bleeding index was 40.7 +/- 23.0%. The papilla bleeding index values of
      the HA group were 1.6 at T1, 1.0 at T2, and 0.7 at T3. The gingival crevicular
      fluid showed significant reductions in the HA group. At T1 the recorded mean
      value was 16.3, at T2 it was 11.8, and at T3 it was 7.9. Only insignificant
      changes were observed in the respective indices of the control group. There were
      no significant alterations in the plaque values of either group throughout the
      study period. CONCLUSION: The results obtained by this study demonstrate that the
      topical application of an HA-containing preparation represents a potentially
      useful adjunct in the therapy of gingivitis, although its use does not diminish
      the need for plaque reduction as a primary therapeutic measure.

PMID- 15999422
TI  - Homage to Prof. M.G. Replacement: a celebration of structural biology at Purdue
      University.
AB  - On a glorious spring day in the American Midwest, friends, colleagues,
      collaborators, and alumni of Prof. M.G. Replacement gathered together at the
      campus of Purdue University, West Lafayette, Indiana to celebrate 40 years of
      structural biology and honor the man behind it all: M.G. Rossmann. The date also
      corresponded approximately to MGR's 75th birthday. It was a memorable occasion
      for several reasons. An earlier meeting 10 years ago did also render homage to
      Michael (New Directions in Protein-Structure Relationships: Symposium in Honor of
      Professor M.G. Rossmann's 65th Birthday, Purdue University, October 21, 1995),
      but on this occasion the symposium was much more encompassing of structural
      biology and had a more global character. A large number of featured speakers
      presented and discussed advances in vast areas of structural biology and came
      from the four corners of the world to share their work with the new generations
      of structural biologists currently being trained at Purdue University.

PMID- 15999423
TI  - Gastroenteritis outbreak among Canadian Forces members: Bosnia-Herzegovina,
      August 2003.

PMID- 15999424
TI  - Statement on new oral cholera and travellers' diarrhea vaccination.

PMID- 15999425
TI  - "Bad law" argument in Morgentaler v. The Queen.
AB  - The issues raised by the Crown on appeal in Morgentaler v. The Queen from the
      acquittal of the accused were rendered moot when the Supreme Court of Canada
      declared the abortion statute (section 251 of the Criminal Code) to be
      unconstitutional. There was no need for the Court to discuss either the issue of
      the use of the "defence of necessity" or defence counsel's "bad law" argument.
      Nevertheless, Chief Justice Dickson found the "bad law" argument of defence
      counsel, Morris Manning, Q.C., "so troubling," he felt "compelled to comment" on
      it. Mr. Manning argued that, although the jury was to take its instructions in
      the law from the judge, it had a right not to apply the law in the case to the
      facts because the abortion statute was "bad law." In his decision, Chief Justice
      Dickson reiterated that it is the duty of the judge to instruct the jury in the
      law and the function of the jury to apply the facts to the law, and that Mr.
      Manning was wrong to tell the jury otherwise. Among other things, the Chief
      Justice used a "racist jury" example to demonstrate Mr. Manning's error. The
      author argues in this comment that the Chief Justice's example was ill-conceived
      and inapposite, and concludes that the jury and Mr. Manning should be commended
      for helping to rid Canada of an oppressive abortion law.

PMID- 15999426
TI  - Impact of age, sex and body mass index on outcomes at four years after gastric
      banding.
AB  - BACKGROUND: Adjustable gastric banding for weight reduction in severely obese
      persons allows reversible individualized restriction during postoperative follow
      up. It is unknown whether preoperative age, sex and BMI might modulate treatment
      outcome. METHODS: 404 severely obese patients (79% women; age 42 +/- 0.5 years
      [mean +/- SEM]; BMI 42.1 +/- 0.2 kg/m2) completed 4-year follow-up after banding.
      Weight loss, complications, and Bariatric Analysis and Reporting Outcome System
      (BAROS) scores were recorded prospectively. RESULTS: 4 years after banding,
      younger (<50 years) women lost more weight than older (50 years) men (28.2 +/-
      0.7% vs 19.4+/- 1.6%; P=0.001); older women and younger men lost similar weight.
      Patients with preoperative BMI >50 lost more weight than patients with BMI <35
      (30.5 +/- 2.3% vs 22.8 +/- 2.6%; P=0.03). 22.3% of patients (n=90) had band
      system-related complications. Compared to women, men had more band leaks (7.0% vs
      1.9%; P=0.007), and older men had more band slippages than younger men (8.4% vs
      0.0%; P=0.035). Patients with preoperative BMI >50 were less likely than patients
      with BMI 35-40 or 40-50 to experience gastric complications (10.6%, 18.8%, 23.0%,
      respectively), but more likely to experience port/tube complications (15.8%,
      2.4%, 7.9%, respectively; P<0.055). BAROS scores were different between men and
      women (P=0.05), and between younger and older people (P=0.001). Women and younger
      people were more likely than men and older people to score "very good" (P=0.03,
      P=0.001, respectively). CONCLUSIONS: Adjustable gastric banding is an effective
      intermediate-term treatment for severe obesity. Preoperative age, sex, and BMI
      are important modulators of outcome and should be considered during preoperative
      evaluation.

PMID- 15999427
TI  - The church, the law, and the advancing armies of death.

PMID- 15999428
TI  - Rising to the occasion of our death.

PMID- 15999429
TI  - Making use of the Patient Self-Determination Act.

PMID- 15999430
TI  - [Assessment of human papilloma virus (HPV) testing in primary screening for
      cervical cancer in France (May 2004)].

PMID- 15999431
TI  - Effectiveness and side effects of thiazolidinediones for type 2 diabetes.

PMID- 15999432
TI  - Medicare program; competitive acquisition of outpatient drugs and biologicals
      under Part B. Interim final rule with comment period.
AB  - This interim final rule with comment period implements provisions of the Medicare
      Prescription Drug, Improvement, and Modernization Act of 2003 that require the
      implementation of a competitive acquisition program for certain Medicare Part B
      drugs not paid on a cost or prospective payment system basis. Beginning January
      1, 2006, physicians will generally be given a choice between obtaining these
      drugs from vendors selected through a competitive bidding process or directly
      purchasing these drugs and being paid under the average sales price system.

PMID- 15999433
TI  - Intimate partner violence consensus statement.

PMID- 15999434
TI  - Twin and genetic effects on life events.
AB  - Twin studies that examine the effect of specific environmental risk factors on
      psychiatric disorders assume that there are no differences in prevalences of
      these risk factors between twins and singletons. Violation of this assumption
      signifies that the results from twin studies might not generalize to singletons.
      Another assumption, not only underlying twin studies but also epidemiological
      research, is that life-events are not influenced by familial factors. We tested
      differences in prevalences of experienced life events in a Dutch sample of 1086
      monozygotic (MZ) twins, 2090 dizygotic (DZ) twins and 1307 of their siblings.
      Self reported data on life events (illness of self, illness of a significant
      other, spouse/romantic relationship, divorce/break-up of a relationship, death of
      a significant other, traffic accident, robbery, violent assault, sexual assault)
      were available from a survey-study. We further investigated whether familial
      resemblance was present for the exposure to these life events and, if so, whether
      this resemblance was due to genetic or common environmental factors. No
      differences were found in the prevalences of life events between MZ twins, DZ
      twins and their siblings. There was evidence for familial aggregation of all life
      events, except for traffic accidents in women. Results indicated genetic control
      on the presence of a spouse or involvement in a relationship. Familial
      resemblance of illness and death of a significant other was mainly due to common
      environment. For the other life events, it was not possible to distinguish
      between genetic and common environmental effects.

PMID- 15999435
TI  - [The operon: a group of genes with expression coordinated by an operator.
      C.R.Acad. Sci. Paris 250 (1960) 1727-1729].

PMID- 15999436
TI  - Condoms, AIDS & Catholic ethics: open to the transmission of death?

PMID- 15999437
TI  - The right to choose to die with dignity.
AB  - Advances in medical science have done much to improve the quality of life but in
      some cases medical treatment may result in the prolonging of death rather than
      the enhancement of life. Patients may wish to refuse or withdraw from medical
      treatment even though they realise that this will lead to an early death. Medical
      attendants may, however, see it as their legal or ethical duty to impose medical
      treatment in the interest of preserving life. At a broad level two crucial
      interests come into headlong conflict--the patient's right to self-determination
      and society's interest in the preservation of human life. In this article the
      legal principles which are invoked to resolve this conflict both at common law
      and under recent Victorian legislation, the Medical Treatment Act 1988, are
      discussed and the thesis advanced that, in relation to competent patients, the
      law favours the right to self-determination.

PMID- 15999438
TI  - Abortion legislation after Webster v. Reproductive Health Services: model
      statutes and commentaries.
AB  - The following Article analyzes the United States Supreme Court's examination of
      abortion rights in Webster v. Reproductive Health Services. The Article then
      proposes model statutes restricting abortion in light of the Webster decision.
      The Cumberland Law Review invites and encourages commentary on both sides of the
      issue.

PMID- 15999439
TI  - State constitutional privacy rights post Webster--broader protection against
      abortion restrictions?

PMID- 15999440
TI  - AAMI advice on reprocessing instructions.

PMID- 15999441
TI  - Toward a standard of informed consent by the adolescent in medical treatment
      decisions.

PMID- 15999442
TI  - Dead complicated.

PMID- 15999443
TI  - High-Dose Vitamin E Supplementation and Mortality.

PMID- 15999444
TI  - The HIT parade.

PMID- 15999445
TI  - Hail e-mail. Case study: e-mail can solve communication difficulties.

PMID- 15999446
TI  - MGMA Board approves pay-for-performance principles.

PMID- 15999447
TI  - Did you get bang for the buck? Case study: evaluating a training decision.

PMID- 15999448
TI  - The shadow coach: high-touch help for low-scoring providers.

PMID- 15999449
TI  - Ease on down the road. Start technology implementation with care and foresight.
AB  - The electronic health record (EHR) is all about change. To keep your practice
      moving forward technologically, determine your objective for an EHR, evaluate
      various systems' components and drive the selection process toward the solution
      that will meet your objectives. The author gives a low-stress, low-investment
      prescription for incorporating an EHR into your practice.

PMID- 15999450
TI  - Early input makes for successful system output. Get executives involved early for
      system implementation decisions.
AB  - Key decisions made upfront by a medical group's executive team and a clear
      understanding of organizational goals and objectives provide critical information
      for the people designing and testing a new information system. Before diving into
      the design sessions that provide the requirements for building the system, three
      key meetings with the executive team must take place. Those meetings--and their
      outcomes--set the tone for success.

PMID- 15999451
TI  - The re-emergence of the IDS practice model. Cost-driven and community-focused.
AB  - Physicians, hospitals and other providers are revisiting the concept of the
      integrated delivery system (IDS) to confront two challenges likely to remain
      fixtures on the health care landscape for some time: increasing competition and
      decreasing medical reimbursement. Forming an IDS often presents a standard set of
      hurdles for physicians, administrators and staff, but once barriers are overcome,
      this type of health care delivery system can provide substantial benefits to a
      community.

PMID- 15999452
TI  - New IDS models share the same challenges.

PMID- 15999453
TI  - Tsunami relief.

PMID- 15999454
TI  - Ecology of mosquitoes of Midwestern Nigeria.
AB  - BACKGROUND & OBJECTIVES: The ecology and distribution of various mosquito species
      is important in the determination of mosquito vector abundance and associated
      diseases prevalence. The distribution of various mosquito genera in natural and
      artificial habitats and their relative species abundance was studied between
      August 2002 and July 2003 in three foci (Uromi, Ekpoma and Auchi) comprising the
      Esan and Etsako regions of Midwestern Nigeria. METHODS: Sampling was carried out
      by the method of Hopkins (1952) by dipping using a pipette or ladle depending on
      container types. Pooled contents of smaller containers were sampled with a pond
      net. All breeding sources of mosquito larvae were grouped into five (5) depending
      on their nature, constitution and the physiochemical properties. Artificial
      mosquito cultures were also carried out in four different container types;
      plastics, metal cans, earthenware pots and bamboo strips, in parts of two
      different macro habitats subdivided into area of high human activities (AHHA) and
      areas of derived/secondary vegetation (ADSV). Environmental temperatures,
      rainfall and relative humidity were monitored during the study. RESULTS: The
      present study revealed 17 mosquito species belonging to three genera (Anopheles,
      Culex and Aedes) which are potential vectors of four human diseases in the areas
      surveyed. A total of 736 mosquito larvae were encountered in artificial sources
      and 568 larvae were harvested from natural sources. Pools, plastics and metal
      cans were the predominant artificial sources of mosquito larvae. CONCLUSION: The
      contribution of human activities and increasing environmental modification to the
      breeding of human disease vector mosquitoes is of importance and selective vector
      control measures including larviciding are recommended particularly before onset
      of rainy season.

PMID- 15999455
TI  - Frequency-dependent prey-selection of predacious water bugs on Armigeres
      subalbatus immatures.
AB  - BACKGROUND & OBJECTIVES: The predatory behaviour with reference to the frequency
      dependent prey-selection of the water bugs Sphaerodema annulatum Fabricius and S.
      rusticum Fabricius was studied in the laboratory using the IV instar larvae and
      pupae of Armigeres subalbatus as prey to ascertain their efficacy as predator of
      mosquito immatures. METHODS: Field collected adult morphs of the water bugs were
      allowed to predate on larvae and pupae provided in different ratios and densities
      as per the model of Greenwood and Elton' for a fixed time period. The data
      obtained on their predation rate were analysed with respect to the model
      parameters, lnV--the frequency independent component and b--the frequency
      dependent component of selection. RESULTS: It was found that the prey-selection
      was dependent on the relative numbers of prey available, favouring apostatic
      selection. The b values and lnV values for S. annulatum were 0.54 +/- 0.01 and
      0.92 +/- 1.04 respectively whereas the corresponding values for S. rusticum were
      0.71 +/- 0.03 and 0.17 +/- 1.57 respectively. INTERPRETATION & CONCLUSION: The
      selection of preys by the water bugs was dependent on the relative number of the
      prey forms and thus they are expected to predate on the form more abundant in a
      heterogeneous prey population and adversely affect the adult emergence.

PMID- 15999456
TI  - A comparative study on the susceptibility of male and female albino mice to
      Trypanosoma brucei brucei.
AB  - BACKGROUND & OBJECTIVES: Trypanosomiasis has remained a major set-back in the
      development of livestock farming in tropical Africa. Thus the need for
      ascertaining the trypanotolerant levels of domestic animal breeds and possible
      improvement on them cannot be over-emphasised. METHODS: Level of trypanotolerance
      in animals was compared between sexes using albino mice infected with a Nigerian
      strain of Trypanosoma brucei brucei at a 50% mouse lethal dose (MLD50). RESULTS:
      The male mice showed unrestrained parasite growth with a prepatent period (PP) of
      two days and a mean survival period (MSP) of six days corresponding to a gradual
      decrease in packed cell volume (PCV), body weight, diet response and white blood
      cells (WBC) count to the time of death. Their female counterparts showed a PP of
      three days and MSP often days with a similar PCV gradient but a refractory WBC
      count. There was no significant difference in the differential leucocytes count
      in both sexes. However, the eosinophils count was significantly higher in the
      infected animals. It was found that female albino mice exercised more parasite
      restraint than their male counterparts. INTERPRETATION & CONCLUSION: The result
      suggests that the female animals may be more trypanotolerant hence may be more
      useful in protein production in trypanosomiasis endemic areas. However, further
      research using large domestic breeds like goats and sheep may be required to
      confirm the hypothesis.

PMID- 15999457
TI  - The prevalence of malaria parasitaemia in blood donors in a Nigerian teaching
      hospital.
AB  - BACKGROUND & OBJECTIVES: The present study was undertaken to assess the
      prevalence of malaria parasitaemia among blood donors and to determine the
      possible risk of transmission of malaria parasite to recipients of blood in
      Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State. METHODS: Four
      hundred and forty-four subjects were selected randomly and EDTA added blood was
      collected for screening malaria parasites using Giemsa stain. The data were
      subjected to chi2 analysis. RESULTS: Prevalence of malaria was 30.2% among blood
      donors and showed bimodal distribution with significant variation in different
      months. INTERPRETATION & CONCLUSION: Due to high prevalence of asymptomatic
      malaria parasitaemia in this region, all blood samples should be screened for
      malaria parasites (post-donor screening) and administered with a curative dose of
      antimalarials prophylactically to all patients transfused with malaria parasite
      positive blood.

PMID- 15999458
TI  - Entomological studies on malaria in irrigated and non-irrigated areas of Thar
      desert, Rajasthan, India.
AB  - BACKGROUND & OBJECTIVES: Malaria is the major health problem in western Rajasthan
      yet its vector fauna and transmission dynamics thereof is not understood
      properly. The present investigations report complete profile of qualitative and
      quantitative aspects of anopheline species occurring in different settings of
      desert ecosystem. METHODS: Area with irrigation through canal for more than 20
      years (setting I), area with irrigation through canal for 10 years (setting II)
      and area without any irrigation (setting III) have been selected for studies.
      Species identification and their densities (per man hour) was made as per
      standard methods. RESULTS: In village of setting I, during rainy season, An.
      subpictus and An. stephensi were present while during winter season four species-
      An. subpictus, An. stephensi, An. culicifacies and An. annularis were collected.
      In all the villages of setting I, II and III no Anopheles mosquito was observed
      during summer season. In the villages of desert region without any irrigation
      facilities through any canal, the anopheline species were present only during
      rainy season. INTERPRETATION & CONCLUSION: An. stephensi is the major malaria
      vector of desert irrespective of whether the area is canal irrigated or not.
      During summer season absence of vector species in all the villages require
      further studies on micro-ecology of the species under desert conditions.

PMID- 15999459
TI  - Knowledge, awareness and practices towards malaria in communities of rural, semi
      rural and bordering areas of east Delhi (India).

PMID- 15999461
TI  - Effect of amlodipine and lacidipine on left ventricular diastolic and long axis
      functions in arterial hypertension and stable angina pectoris.
AB  - OBJECTIVE: Impaired left ventricular (LV) diastolic and long axis functions are
      common in arterial hypertension and stable angina pectoris patients despite
      normal LV ejection fraction. Data concerning the effect of calcium channel
      blockers (CCB) on the LV long axis function in this context are lacking. METHODS
      AND RESULTS: Fifty-nine hypertensive patients with associated coronary artery
      disease (stable angina pectoris) and isolated diastolic dysfunction were
      randomized to receive amlodipine (30 patients) or lacidipine (29 patients) for 4
      weeks. Clinical investigation, exercise testing, echocardiography were performed
      before and after the active treatment period. LV diastolic function was analysed
      from transmitral flow using Doppler echocardiography. Mitral annulus motion was
      investigated for LV long axis function analysis using 2-D guided M-mode
      echocardiography (amplitudes of motion) and pulsed wave tissue Doppler
      (velocities). Amlodipine and lacidipine affected LV diastolic and long axis
      functions differently: during treatment with amlodipine isovolumic relaxation
      time (IVRT) and deceleration time of LV early filling (DT) decreased (IVRT--from
      93 +/- 19 ms to 79 +/- 15 ms, DT--from 206 +/- 36 ms to 188 +/- 27 ms; p < 0.05),
      early diastolic velocity of mitral annulus motion (E') increased (from 10.0 +/-
      1.9 cm/s to 10.8 +/- 1.8 cm/s after treatment; p < 0.05). Lacidipine did not
      significantly change these parameters (IVRT-- 88 +/- 15 ms before, 87 +/- 13 ms
      after treatment, DT--214 +/- 34 ms and 218 +/- 42 ms, E'-- 10.4 +/- 1.5 cm/s and
      10.6 +/- 1.5 cm/s, respectively). More favourable effects of CCB on LV long axis
      function was found in patients with post-systolic shortening. CONCLUSIONS:
      Amlodipine can improve diastolic and long axis functions of the left ventricle in
      patients with arterial hypertension and stable angina pectoris.

PMID- 15999460
TI  - Tinospora cordifolia as an adjuvant drug in the treatment of hyper-reactive
      malarious splenomegaly--case reports.
AB  - BACKGROUND & OBJECTIVE: The effect of aqueous extract of Tinospora cordifolia, an
      immunomodulator with antimalarial activity along with chloroquine was studied in
      the treatment of three cases of hyper-reactive malarious splenomegaly in District
      Hospital, Daltonganj town, Jharkhand, India. These cases were partial/slow
      responders to the conventional antimalarial drug chloroquine. METHODS: Aqueous
      extract of T. cordifolia (500 mg) was added to chloroquine (CQ) base (300 mg)
      weekly and CQ prophylaxis was observed up to six months. Improvement was gauzed
      by measuring spleen enlargement, Hb, serum IgM and well-being in three cases of
      hyper-reactive malarious splenomegaly. RESULTS: Addition of extract of T.
      cordifolia for the first six weeks to chloroquine showed regression of spleen by
      37-50% after six weeks and 45-69% after six months from the start of treatment.
      Likewise decrease in IgM and increase in Hb as well as wellbeing (Karnofsky
      performance scale) were observed. CONCLUSION: The results of the present study
      paves a new sight in the treatment of hyper-reactive malarious splenomegaly,
      however, large-scale trial is required to confirm the beneficial effect of T.
      cordifolia extract in combination with chloroquine.

PMID- 15999462
TI  - Quality assessment of oral anticoagulation in Belgium, as practiced by a group of
      general practitioners.
AB  - OBJECTIVE: In Belgium oral anticoagulation therapy is mainly supervised by
      general practitioners (GPs). This study aims to evaluate the quality of
      management of oral anticoagulation by Belgian GPs and to verify the relation
      between time in range and a set of potentially influencing co-variables. METHODS:
      In a retrospective cross-sectional study, involving 66 GP-practices, the INR
      values obtained over a 6-month period were analysed. All INR-values were
      determined by a single clinical laboratory and additional medical information was
      provided by the GPs. Linear mixed models have been used to model the patient
      specific percentage INR in target as a function of different co-variables.
      RESULTS: 737 patients were included in the study. Patients who underwent a
      surgical intervention with an interruption of the anticoagulation during the
      study were excluded. Patients were only included after the initial starting-up
      period. 5890 INR-values were obtained. A total of 92,566 days of therapy was
      evaluated. 50% of the day values were within 0.5 INR-units from target (and 66%
      within 0.75 INR-units from target). In a multiple regression model, a significant
      relation between the percentage of time in range and the target INR (2.5 or 3.5)
      and the gender of the patient was shown. The incidence rate for major bleeding
      was 5.5/100 patient years (and 3.5/100 patient years for thrombo-embolic events).
      CONCLUSION: The quality of management of oral anticoagulation by the GPs in
      Belgium is suboptimal. It is unknown whether interventions such as guidelines,
      feedback, point-of-care monitoring and computer-assisted anticoagulation
      monitoring could improve the results.

PMID- 15999463
TI  - Hypotensive effect of dopamine: synergism induced by fenoldopam or levodopa.
AB  - OBJECTIVE: The effects of the co-administration of fenoldopam (FD) or levodopa
      (LD) with dopamine (DA) on arterial blood pressure were studied in rats to assess
      the possibility of synergic effects that might be of some clinical importance.
      METHODS AND RESULTS: Mean arterial blood pressure (MBP) in the carotid artery of
      anaesthetized rats was registered. All agents induced dose-dependent reductions
      in mean arterial blood pressure when administered in a non-cumulative schedule to
      rats pretreated with phentolamine. For each drug, the doses that induced a 50% of
      reduction in basal mean arterial blood pressure, (ED50) calculated by standard
      linear regression analysis of the log dose-response curve and were 5.49 mg/kg,
      (n=10), 2.86 mg/kg, (n=11) and 0.445 mg/kg, (n=12), for FD, LD and DA,
      respectively. The interactions were evaluated by simultaneous administration of
      different fixed ratios of DA with FD (1:12.3) or DA with LD (1:6) and obtaining
      dose-response curves and ED50's for each mixture. An isobolographic analysis was
      then performed, which demonstrated that the co-administration had synergistic
      effects as illustrated by statistically higher reductions of blood pressure under
      each combination as compared to theoretical calculated additive effects.
      CONCLUSIONS: The present results show that in the rat, after alpha-adrenergic
      blockade, the association of DA and FD could inappropriately potentiate the
      hypotension induced by both drugs.

PMID- 15999464
TI  - Status of intracellular and extracellular magnesium concentration in patients
      with cardiac syndrome X.
AB  - OBJECTIVES: This study sought to clarify the differences of intracellular and
      extracellular magnesium levels in patients with cardiac syndrome X. METHODS: We
      evaluated the intracellular and extracellular magnesium status of 22 patients
      with cardiac syndrome X (group A) and 22 age--and gender--matched disorder-free
      control subjects (group B). Levels of magnesium were determined in serum, urine,
      erythrocytes, and the 24-h magnesium retention rate was calculated by a magnesium
      loading test. RESULTS: Group A showed a higher 24-h magnesium retention rate
      (49.8 +/- 1.3% vs. 32.6 +/- 7.5%, p < 0.05) and a lower intracellular
      concentration of magnesium in erythrocytes than group B (3.7 +/- 1.4 vs. 5.6 +/-
      1.3 fg/cell, p < 0.05), demonstrating the presence of magnesium deficiency in
      group A. There were no significant differences in the serum concentration of
      magnesium between groups A and B (0.87 +/- 0.23 vs. 0.83 +/- 0.15 mmol/l).
      CONCLUSIONS: This study demonstrated that the intracellular magnesium level
      decreased in patients with cardiac syndrome X.

PMID- 15999465
TI  - The effect of orlistat-induced weight loss on interleukin-6 and C-reactive
      protein levels in obese subjects.
AB  - OBJECTIVE: Inflammation plays a major role in the pathogenesis of
      atherosclerosis. Obesity is an independent risk factor for cardiovascular
      disease, which may be mediated by increased secretion of proinflammatory
      cytokines by adipose tissue. The aim of this study is to investigate changes in
      the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive
      protein (hs-CRP) during weight reduction with orlistat treatment in obese
      patients. METHODS AND RESULTS: Thirty-six obese (BMI: 36.1 +/- 3.4 kg/m2) and II
      non-obese (BMI: 22.9 +/- 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels
      were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg
      three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of
      circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in
      the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05)
      and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the
      level of obesity assessed by BMI at baseline. After 6 months of orlistat
      treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg,
      the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with
      significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels.
      CONCLUSION: In summary plasma IL-6 and hs-CRP levels were increased in obese
      patients. Orlistat-induced weight reduction was associated with decreasing levels
      of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be
      directly involved in atherogenesis, this would suggest that interventions to
      reduce IL-6 and CRP levels could be cardioprotective.

PMID- 15999466
TI  - Dietary consumption of green tea catechins attenuate hyperlipidaemia-induced
      atherosclerosis and systemic organ damage in mice.
AB  - OBJECTIVE: The effects of consuming green tea catechins on the development of
      hyperlipidaemia-induced systemic organ damage have not been well studied; we
      investigated the effect using low density lipoprotein receptor knockout mice.
      METHODS AND RESULTS: Mice were treated with high cholesterol food containing 0.2
      or 4% catechins and they were supplemented for 35 weeks. High plasma cholesterol
      levels, liver and renal dysfunctions were observed in no catechin fed mice, while
      chow containing catechin suppressed these levels and damages. Severe
      atherosclerosis of the aorta, fatty liver and renal injury were also shown in the
      control mice; inflammatory factors were enhanced in these lesions of nontreated
      mice. The lesions were attenuated with suppression of the inflammatory factors in
      the chow-contained catechin treatment group. CONCLUSION: Dietary consumption of
      tea catechins attenuated the development of the systemic organ damage; thus, this
      has a clinical effect against systemic inflammatory diseases.

PMID- 15999467
TI  - Differentiation, engraftment and functional effects of pre-treated mesenchymal
      stem cells in a rat myocardial infarct model.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) offer a novel therapeutic option in the
      treatment of acute myocardial infarction. MSCs are able to differentiate into
      myogenic cells after 5-azacytitdine treatment. However, 5-azacytidine might have
      genotoxic effects. Recently, it was reported that combined treatment with bone
      morphogenetic protein-2(BMP-2) and fibroblast growth factor-4(FGF-4) caused
      cardiac differentiation in non-precardiac mesoderm explants. Therefore, we
      investigated whether MSCs treated with combined BMP-2 and FGF-4 showed evidence
      of myogenic differentiation in vitro, and whether these cells resulted in
      sustained engraftment, myogenic differentiation, and improved cardiac function
      after implantation in infarcted myocardium. METHODS AND RESULTS: In vitro study:
      MSCs were treated with BMP-2 + FGF-4 (GF-MSCs) and myogenic phenotype was
      evaluated immunohistochemically. Cell growth curve was used to compare MSC
      proliferative capacity between the growth factors and 5-azacytidine treatments.
      In vivo study: two weeks after coronary artery occlusion, GF-MSCs (n=15), MSCs
      (n=5) labelled with PKH26 were injected into infarcted myocardium. Control
      animals (n=5) received a culture medium into the infarcted myocardium. Two weeks
      after implantation, some engrafted GF-MSCs or MSCs expressed sarcomeric-alpha
      actinin and cardiac myosin heavy chain, as was observed in culture.
      Echocardiography showed that the GF-MSC group had a better (p < 0.05) left
      ventricular performance than the other groups. CONCLUSION: GF-MSCs induced
      myogenic differentiation in vitro. Moreover, GF-MSCs engrafted into the infarcted
      myocardium increased myogenic differentiation, prevented dilation of the
      infarcted region, and eventually improved heart function.

PMID- 15999468
TI  - Does leukofiltration reduce pulmonary infections in CABG patients? A prospective,
      randomized study with early results and mid-term survival.
AB  - BACKGROUND: We present the first prospective randomized study of primary coronary
      artery bypass grafting (CABG) patients who were analyzed for postoperative
      infections after undergoing blood and/or blood product transfusion (BBPT) with a
      Pall Purecell leukoreducing filter. METHODS AND RESULTS: One hundred and four
      patients were enrolled between March 1998 and March 1999. Seventy-two of the
      patients received BBPT (average 5.6 units BBPT/filter patient and 5.6
      units/control patient). Three patients who had CABG without extracorporeal
      circulation or mixed transfusions of filtered and unfiltered BBPT were excluded.
      The remaining 69 transfused patients (38 filtered, 31 control) were analyzed and
      the incidence of culture proven infections was recorded. Mid-term survival data
      were obtained from the National Death Index and Kaplan-Meier survival plots were
      constructed. All patients were stratified and matched according to the
      EuroSCORE.Thirty-day mortality was 2.6% and 3.2% for the filtered and control
      patients, respectively. There were 5 cases of culture proven infections in 38
      filtered patients (13.2%) and 8 in 31 controls (25.8%), P = 0.224. No pulmonary
      tract infections were recorded in the filter group vs. 4 (12.9%) in controls, P =
      0.048. Reduced length for mechanical ventilation (16.3 hours vs. 57.8, P =
      0.103), length of stay (9.1 vs. 10.8 days, P = 0.685), as well as increased 50
      month actuarial survival, (45.5 vs. 42.3 months, P=0.695) in filtered vs.
      control, respectively, were recorded. CONCLUSIONS: The use of leukoreduced BBPT
      reduced the incidence of pulmonary tract infections in patients undergoing CABG.

PMID- 15999469
TI  - Total flavones from Elsholtzia blanda reduce infarct size and improve heart
      function during acute myocardial infarction by inhibiting myocardial apoptosis in
      canines.
AB  - OBJECTIVE: The current study tests the hypothesis that inhibition of apoptotic
      cell death with total flavones from Elsholtzia blanda (TFEB), a traditional
      Chinese medicine, reduces infarct size and improves heart function during
      myocardial ischaemia induced by coronary occlusion in canines. METHODS AND
      RESULTS: Myocardial apoptosis was detected by the TdT-mediated dUTP nick end
      labelling (TUNEL) method and DNA laddering. Infarct size of the left ventricle,
      serum level of CK-MB, haemodynamic parameters including rate of rise and decline
      of left ventricular pressure (+/- dp/dtmax), left ventricular systolic pressure
      (LVSP), main arterial pressure (MAP), coronary blood flow (CBF), coronary
      vascular resistance (CVR) were measured in this study. TUNEL positive cells were
      markedly reduced from 27.83 +/- 8.15% in the control dogs to 7.74 +/- 3.50% in
      the TFEB-treated ones (P < 0.01), consistent with the absence of DNA laddering.
      TFEB significantly reduced infarct size from 19.30 +/- 6.66% in the control dogs
      to 8.87 +/- 1.66% (P < 0.01), confirmed by lower serum CK-MB activity. TFEB
      significantly reduced MAP and CVR. The decrease in +/- dp/dtmax, LVSP and CBF
      also tended to be much smaller in the TFEB treated group. CONCLUSION: These data
      suggest that the inhibitory effect of TFEB on apoptosis during coronary occlusion
      is associated with reduction in infarct size and improvement in heart function.

PMID- 15999470
TI  - Plasma BNP levels are determined by the severity of left ventricular systolic
      dysfunction but not the types of underlying heart disease.
AB  - OBJECTIVES: The primary aim of the study was to investigate whether there is a
      difference in plasma B-type natriuretic peptide (BNP) levels among the left
      ventricular systolic dysfunction caused by different types of heart disease.
      METHODS AND RESULTS: Plasma BNP was measured in patients with left ventricular
      systolic dysfunction as a result of mitral valve regurgitation (n=26),
      hypertension (n=36), coronary heart disease (n=37) and dilated cardiomyopathy
      (n=32). The left ventricular end-diastolic diameter and ejection fraction were
      assessed with echocardiography. The valvular heart disease group had more women
      and was younger (p < 0.05). There was no significant difference in the New York
      Heart Association functional class, left ventricular end-diastolic diameter and
      ejection fraction among the four groups (p < 0.05). The average plasma BNP was
      also similar among the four groups of patients. In each group, a significant
      correlation between the levels of BNP and the left ventricular end-diastolic
      diameter or ejection fraction was identified (p < 0.001). CONCLUSION: Plasma BNP
      concentrations during left ventricular systolic dysfunction are associated with
      left ventricular diameter and function, but they are not determined by the causes
      of the heart failure.

PMID- 15999471
TI  - Oestrogen receptor dinucleotide (TA) polymorphism affects total and LDL
      cholesterol but does not predict premature myocardial infarction in Caucasian
      men.
AB  - OBJECTIVE: The aim of this association study was to test the hypothesis whether
      the oestrogen receptor gene dinucleotide (TA) polymorphism is a risk factor for
      premature myocardial infarction in Caucasian men. Moreover, we investigated an
      association between oestrogen receptor gene dinucleotide (TA) polymorphism and
      serum lipid levels. METHODS AND RESULTS: One hundred and thirty men with
      premature myocardial infarction were compared with healthy men. Cases and
      controls did not demonstrate a statistically significant difference in
      distribution of the oestrogen receptor dinucleotide (TA) gene polymorphism
      alleles. Neither did we demonstrate the length of the dinucleotide (TA) repeats
      of the oestrogen gene to be associated with premature myocardial infarction in
      Caucasian men. Subjects with larger alleles (both alleles of > or =19 repeats)
      differed from subjects with other genotypes in serum total and LDL cholesterol,
      but not in HDL cholesterol and triglycerides. CONCLUSIONS: Despite an association
      between the oestrogen receptor gene dinucleotide (TA) polymorphism in the
      regulatory region of the alpha oestrogen receptor gene and serum total and LDL
      cholesterol, our study suggests that the oestrogen polymorphism is not associated
      with premature myocardial infarction in Caucasian men.

PMID- 15999472
TI  - Midterm follow-up after off-pump versus on-pump coronary artery bypass grafting.
      Results from a case-matched study.
AB  - OBJECTIVE: Early survival in off-pump coronary artery bypass (OPCAB) patients is
      reported to be as good as that of conventional coronary artery bypass grafting
      (CABG). However, it remains unknown whether midterm cardiac outcome after off
      pump surgery is similar to that for the on-pump procedure. METHODS AND RESULTS:
      One hundred OPCAB patients (67.8 (9.3) y) were compared to a case-matched
      contemporary group of CABG patients (69.4 (8.8) y). In-hospital and midterm
      outcome data are presented. Follow-up was 100% complete. The mean number of
      distal anastomoses per patient was 1.9 (0.8) and 2.4 (1.0) in the OPCAB and CABG
      group, respectively. Grafting according to treatment plan was 100% in both
      groups. Peak creatine kinase muscle-brain and cardiac troponin I (cTnI) release
      were similar in the overall groups, but the cTnI release in the 25 most recently
      operated patients was significantly lower in the OPCAB group (4.8 (9.1) ng/ml vs.
      14.0 (20.5) ng/ml, p = 0.04). Duration of mechanical ventilation, ICU stay and
      hospital stay were shorter in the OPCAB group. The incidence of atrial
      fibrillation was similar. There were no differences in in-hospital complications.
      The actuarial survival at 1, 3 and 5 years was 88% (C.I. 81.6 to 94.3), 78% (C.I.
      66.1 to 90.2) and 78% (C.I. 66.1 to 90.2) in the OPCAB and 90% (C.I. 84.0 to
      95.9), 84% (C.I. 74.6 to 92.5) and 68% (C.I. 44.7 to 90.6) in the CABG group (log
      rank p-value = 0.96). Event-free survival at 1, 3, 5 years was 85% (C.I. 77.8 to
      91.9), 71 % (C.I. 57.4 to 84.2) and 71 % (C.I. 57.4 to 84.2) in the OPCAB and 85%
      (C.I. 77.8 to 91.9), 72% (C.I. 61.1 to 82.7) and 58% (C.I. 37.2 to 78.8) in the
      CABG group (log rank p-value = 0.63). Recurrence of angina (3%) and need for
      reintervention (2%) in the OPCAB group were low. CONCLUSIONS: OPCAB surgery is a
      safe and reproducible technique, yielding short-and midterm outcomes comparable
      to conventional CABG.

PMID- 15999473
TI  - Circadian blood pressure variability is associated with autonomic and baroreflex
      mediated modulation of the sinoatrial node.
AB  - OBJECTIVE: The day-night variability of blood pressure (BP) is of interest in the
      analysis of ambulatory blood pressure monitoring (ABPM). The aim of this study
      was to investigate whether the nocturnal BP reduction was associated with the
      autonomic and baroreflex-mediated modulation of the sinoatrial node in
      normotensive and hypertensive subjects. METHODS AND RESULTS: 63 consecutive
      untreated male subjects (40 hypertensive and 23 normotensive) were studied.
      Spectral parameters of RR interval variability and the alphaLF index (a measure
      of baroreflex gain) were calculated at rest. Then all the subjects performed a 24
      h ABPM. RESULTS: As regards the relationships involving 24-h BP and resting heart
      rate (HR) and HR variability parameters, a significant correlation was found
      between mean RR and both systolic and diastolic nocturnal BP falls (r = 0.40, p <
      0.001, r = 0.32, p < 0.01, respectively); moreover, a significant correlation was
      found between the nocturnal fall of systolic BP and both the LF/HF ratio and
      absolute power of HF (r = -0.25, p < 0.05 and r = 0.29, p < 0.05, respectively).
      The alphaLF index was significantly associated with the nocturnal diastolic BP
      fall (r = 0.26, p < 0.05) whereas the association with the systolic fall did not
      reach statistical significance (r = 0.23, p = 0.07). CONCLUSIONS: The
      relationship found between the nocturnal reduction of BP and both the LF/HF ratio
      and HF power of RR variability suggests that factors influencing the sympatho
      vagal modulation to the heart are associated with the day-night variability of
      blood pressure. Moreover, the relationship between BP fall and the spontaneous
      baroreflex sensitivity index alphaLF, may indicate a role of the baroreflex
      mediated arc function in the BP adjustments occurring during the night.

PMID- 15999474
TI  - Association of coronary atherosclerosis with insulin resistance in patients with
      impaired glucose tolerance.
AB  - OBJECTIVES: The purpose of the study was to evaluate the role of insulin
      resistance (IR) in the development of coronary atherosclerosis in patients with
      impaired glucose tolerance. METHODS AND RESULTS: The study group consisted of 42
      patients with impaired glucose tolerance. Based upon coronary angiography the
      patients were divided into group A--with prior myocardial infarction and critical
      coronary stenosis (n=20) and group B--without prior myocardial infarction and
      without critical coronary stenosis (n=22). In each patient glucose disposal rate
      (GDR) during metabolic clamp, insulinaemia in the fasting state and during the
      clamp, glycaemia during oral glucose tolerance test (OGTT), BMI and body mass
      composition were measured. The groups did not differ in age, BMI, percent fat
      content and distribution, and blood pressure. Fasting insulinaemia (56.7
      microU/ml) was higher in group A than in group B (22.3 microU/ml). GDR in group A
      (2.96 mg/kg b.m./min) was lower than in group B (5.36 mg/kg b.m./min). There was
      a negative correlation between the number of critically narrowed coronary vessels
      and GDR in group A. GDR below 3.97 mg/kg b.m./min was found, based on regression
      analysis, to be a powerful risk factor for myocardial infarction. CONCLUSIONS:
      The relationship between IR and severity of coronary atherosclerosis implies its
      unfavourable role in the development of atherosclerosis. The present findings
      indicate a negative role of IR in the development of myocardial infarction and
      suggest that it is an independent risk factor, which identifies high-risk
      patients requiring treatment that would increase tissue insulin sensitivity.

PMID- 15999475
TI  - Changes in left ventricular outflow and intraventricular flow patterns in
      hypertension and controls: a Doppler echocardiographic study.
AB  - OBJECTIVE: It has been previously reported that intraventricular flow patterns in
      some hypertensive patients with left ventricular hypertrophy, change to patterns
      similar to flow profiles of hypertrophic cardiomyopathy. The purpose of the study
      was to assess left ventricular outflow and mid-septal intraventricular flow
      patterns in hypertensive and normotensive patients. METHODS: Left ventricular
      outflow and mid-septal flows of 68 patients (41 men, mean age 53 +/- 14 years)
      and 45 non-hypertensive healthy controls (26 men, mean age 43 +/- 16 years) were
      assessed with Doppler echocardiography. Acceleration slope, pre-ejection period
      (PEP), and velocity-time integrals of the flows were recorded at the level and 1,
      2 and 4 cm below the aortic valve. M-mode parameters of left ventricular wall
      thicknesses, dimensions and ejection fractions were also recorded. The data was
      analysed with the paired Student's t test with pre-hoc Bonferoni correction of
      the level of significance (0.05/4 = 0.0125) for multiple comparisons. RESULTS: In
      normotensive patients the acceleration slope uniformly and statistically
      significantly decreased beneath the aortic annulus and PEP was unchanged. In
      hypertensive patients the acceleration slope steepened (1596 +/- 531 vs. 1948 +/-
      700 cm/sec, p < 0.05) and PEP decreased (108 +/- 23 vs. 98 +/- 20 msec, p < 0.05)
      1 cm below the aortic valve and later reverted to the normal pattern of decrease
      seen in normotensive patients. CONCLUSION: The increase in acceleration slope and
      decrease in PEP in the subvalvular region may represent the changing contraction
      pattern in the hypertensive patients, causing protrusion of the upper septum into
      left ventricular outflow track and may have a role in the genesis of systolic
      murmurs.

PMID- 15999476
TI  - How a left-to-right shunt may protect against haemodynamic deterioration in
      restrictive cardiomyopathy.
AB  - Today, more and more children with complex heart lesions and underlying
      cardiomyopathies reach adulthood. This results in a wide range of new clinical
      problems encountered in later life. In particular, idiopathic restrictive
      cardiomyopathy is initially treated by medication to reduce symptoms, but at end
      stage disease, heart or heart-lung transplantation becomes unavoidable. We
      describe the case of a patient with restrictive cardiomyopathy and a persistent
      extra-cardiac left-to-right shunt, where we hypothesize that the shunt may
      protect against haemodynamic deterioration in end-stage restrictive
      cardiomyopathie.

PMID- 15999477
TI  - Cefuroxime-induced coronary artery spasm manifesting as Kounis syndrome.
AB  - Allergic angina and allergic myocardial infarction (Kounis syndrome) occurring
      during the course of a drug-induced allergic reaction in the absence of
      angiographically stenosed coronary arteries, is rare in clinical practice. This
      paper reports the case of a 70-year-old woman with no significant risk factors
      for coronary artery disease who developed coronary artery spasm after intravenous
      injection of cefuroxime. A subsequent coronary angiogram revealed normal coronary
      arteries (type I variant of the syndrome). The allergic reaction following
      cefuroxime administration seems to have triggered the development of coronary
      artery spasm. Susceptible individuals expressing an amplified mast cell
      degranulation effect may be more vulnerable to coronary artery spasm. The
      clinical implications of this syndrome are also discussed.

PMID- 15999478
TI  - Georgia court rules on hospital-physician recruitment contract. Carswell v.
      Oconee Regional Medical Center.

PMID- 15999479
TI  - [Advances in researches on drug anaphylaxis of the penis].
AB  - Anaphylaxis is one of the most common and harmful of all adverse effects of
      drugs. It has no direct relation to the toxicity and dosage of drugs, but belongs
      to the pathologic immune reaction, directly threatening patients' lives. At
      present, many important advances and breakthroughs have been achieved in the
      researches on drug anaphylaxis of the penis, but many researchers have gone
      hardly any further than reporting the symptoms and treatments of a few individual
      cases, but very few specific substantial researches on penis drug anaphylaxis.

PMID- 15999480
TI  - [Effects of berberine on cyclic GMP and cyclic AMP levels in rabbit corpus
      cavernosum in vitro].
AB  - OBJECTIVE: To further investigate the action mechanisms of berberine (Ber), and
      assess the effects of Ber on the in vitro formation of cGMP and cAMP in the
      isolated rabbit corpus cavernosum. METHODS: Isolated segments of the rabbit
      corpus cavernosum were exposed to different concentrations of Ber, and, the
      dosage-dependent accumulations of cGMP and cAMP were determined in the tissue
      samples by means of 125I radioimmunoassay. Responses of the isolated tissue
      preparations to Ber were compared with those obtained with the reference compound
      sildenafil (Sil). RESULTS: Ber increased cGMP concentrations directly (P < 0.05).
      In the presence of sodium nitroprusside (SNP), a stimulatory agent of cGMP, both
      Ber and Sil increased cGMP with increasing dosage (P < 0.01), the EC, values
      being 1.32 and 0.67 micromol/L respectively. With the same concentration, neither
      Ber nor Sil influenced the cAMP level significantly (P > 0.05). In the presence
      of PGE1, a stimulator of cAMP, Ber and Sil also raised the cAMP level
      concentration (P < 0.01 ), the EC, values being 4.90 (Ber) and 6.53 (Sil)
      micromol/L respectively. CONCLUSION: Ber can increase cGMP and cAMP
      concentrations in the corpus cavernosum smooth muscles, which may contribute to
      its action of relaxing corpus cavernosum smooth muscles.

PMID- 15999481
TI  - [Effects of urokinase-type plasminogen activator on chemotactic responses of
      spermatozoa in vitro].
AB  - OBJECTIVE: To study the effects of the urokinase-type plasminogen activator (uPA)
      on the chemotactic responses of spermatozoa in vitro, and to explore the possible
      action mechanisms of uPA for male infertility. METHODS: The chemotactic responses
      of spermatozoa were measured using spermatozoal accumulation in the capillary.
      According to the gradient directions of chemoattractant concentrations in the
      capillary, the recruits were divided into three groups: Group A (the ascending
      gradient of chemoattractant), Group B (the descending gradient of
      chemoattractant) and Group C (control). The chemoattractant in the capillary and
      the treating fluid in spermatozoal wells of Group A were uPA of different
      concentrations and Hams F-10, respectively, while those of Group B were just
      opposite to Group A, and those of Group C were both Hams F-10. Then the sperm
      densities in different capillaries were measured at different points of time.
      RESULTS: (1) Spermatozoa moved chemotactically following the concentrations of
      uPA. The accumulative action of spermatozoa in Group A was obviously stronger
      than in Groups B and C (P < 0.05 ). (2) The effects of 20 IU/ml uPA on the
      chemotactic responses of spermatozoa were most significant. (3) The sperm
      densities in the three groups increased with time, significantly different at 20
      min and 30 min (P < 0.05). (4) uPA could increase sperm motility and promote
      sperm movement, as well as induce sperm chemotactic responses. CONCLUSION: uPA
      could induce sperm chemotactic responses and increase sperm motility, which is
      presumably one of the action mechanisms of uPA on male infertility.

PMID- 15999482
TI  - [Angiogenesis and regulatory factors in rats with BPH induced by testosterone].
AB  - OBJECTIVE: To study angiogenesis and regulatory factors in the proliferated
      prostatic tissues of Sprague Dawley (SD) rats with BPH induced by testosterone.
      METHODS: Sixteen castrated SD rats, aged 8 weeks and weighing 200 approximately
      250 g, were equally randomized into a model group and a control group, and the
      BPH model was established by subcutaneous injection of testosterone.
      Immunohistochemistry and MIAS (micro-image analysis system) were used to test the
      manifestations of MVD (microvessel density), VEGF (vascular endothelium growth
      factor), flk-1, endostatin, MMP-2 (matrix metalloproteinase-2) and TIMP-2 (tissue
      inhibitor of metalloproteinase-2) in the prostatic tissues of both the model and
      the control groups. Multiple linear regression with the stepwise method was
      adopted to analyze the data. RESULTS: The manifestations of MVD, VEGF, flk-1, MMP
      2, MMP-2/TIMP-2 and VEGF/endostatin in the model group were higher, while that of
      endostatin was lower than in the control group (P < 0.01), and the manifestation
      of TIMP-2 showed no statistical difference between the two groups. The regression
      analysis indicated that MVD was positively correlated to VEGF, VEGF/endostatin
      and MMP-2/TIMP-2 (r = 0.974, 0.986, 0.982, P < 0.05) and negatively correlated to
      endostatin (r = - 0.975, P < 0.05) . CONCLUSION: Testosterone could induce BPH in
      SD rats by increasing MVD and promoting the multiplication of vascular
      endothelial cells after regradation of basement membrane.

PMID- 15999483
TI  - [Comparison of three methods for evaluating acrosome reaction in human
      spermatozoa].
AB  - OBJECTIVE: To find a convenient and exact method for evaluating acrosome reaction
      in human spermatozoa. METHODS: The semen of the normal male was mixed and then
      divided into 6 groups. Coomassie brilliant blue (CBB) staining, chlortetracycline
      (CTC) fluorescence staining and acid phosphatase (ACP) detection were used for
      morphological observation and data analysis of the acrosome status of the human
      sperm treated with or without progesterone. RESULTS: There were obvious
      morphological differences between the acrosome-reaction and acrosome-intact
      spermatozoa in CBB staining and CTC fluorescence staining, and significant
      differences were observed between the experimental and control spermatozoa by the
      three methods (P < 0.05). CONCLUSION: All the three methods can be used to assess
      acrosome reaction in human spermatozoa, but Coomassie brilliant blue (CBB)
      staining is much more convenient and stable.

PMID- 15999484
TI  - [Sodium nitroprusside facilitates human sperm capacitation and acrosome
      reaction].
AB  - OBJECTIVE: To explore the effect of nitric oxide (NO) on human sperm capacitation
      and acrosome reaction (AR). METHODS: Different concentrations of sodium
      nitroprusside (SNP) were added to the sperm suspension from 48 healthy fertile
      men, and the suspension was incubated in 1 x Earle at 37 degrees C for 1 hour.
      Progesterone was used to induce AR for 15, 30, 45 and 60 min, and then acid
      phosphatase (ACP) activity in the suspension before and after capacitation and at
      different time of AR was measured by p-nitrophenyl sodium phosphate assay. In the
      meantime, sperm motile parameters were assayed by CASA to observe sperm
      capacitation and AR. RESULTS: ACP activity and sperm motile parameters increased
      in the 50 approximately 100 nmol/L NO concentration group, showed no significant
      variation in the 150 approximately 200 nmol/L group, and decreased in the 250
      approximately 300 nmol/L group. CONCLUSION: NO can facilitate sperm capacitation,
      AR and sperm motile parameters in low concentration and suppress them in high
      concentration. ACP activity assay of sperm is an objective and reliable method to
      evaluate sperm capacitation and AR in whole sperm population.

PMID- 15999485
TI  - [Effects of hypothermia on antioxidant capacity of rat testes after testicular
      torsion].
AB  - OBJECTIVE: To investigate the effects of hypothermia on the antioxidant capacity
      of rat testes after testicular torsion. METHODS: Twenty-four healthy pubertal
      male Sprague-Dawley rats were randomly divided into three groups of equal number:
      Group A (torsion) , Group B (torsion + hypothermia) and Group C (control). The
      animals were submitted to unilateral 720 degrees testicular torsion, and
      underwent detorsion two hours later. Fourteen days later, the total antioxidant
      capacity (T-AOC) and the level of malonic diethylaldehyde(MDA) were detected with
      spectrophotometer and histological changes were observed by light microscope.
      RESULTS: The T-AOC of Group B was significantly greater than that of Group A (P <
      0.01), but less than that of Group C (P < 0.01). The MDA level of Group B was
      lower than that of Group A (P < 0.01), but higher than that of Group C (P <
      0.05). CONCLUSION: Hypothermia can restrain the production of oxygen free
      radicals following testicular torsion/detorsion in rats, which in turn can
      inhibit lipid peroxidation and increase the survivability of the torsional
      testis.

PMID- 15999486
TI  - [Age and pathological features of 481 prostate cancer patients].
AB  - OBJECTIVE: To investigate the age and pathological features of prostate cancer
      patients in recent years. METHODS: An analysis was made of the age and
      pathological features of 481 cases of prostate cancer pathologically diagnosed
      from January 1998 to April 2004, 39 cases in 1998, 69 in 1999, 73 in 2000, 68 in
      2001, 72 in 2002, 121 in 2003, and 39 in the first four months of 2004. RESULTS:
      The patients ranged in age from 40 to 91 years, averaging 72, 95% between 55 and
      84, and 84.2% over 65 years. Pathologically, 14 cases were well, 29 moderately,
      and 83 poorly differentiated according to the three-grade system (WHO, the
      Mostofi system), with 355 cases ungraded. Forty cases (8.3%) were microcarcinoma
      (< 1 cm), and 20 cases (4.2%) incidental carcinoma. Of the total number, 473
      cases (98.1%) were pathologically diagnosed as adenocarcinoma, 1 endometrioid
      adenocarcinoma, 1 squamous cell carcinoma, 1 signet ring cell carcinoma, 1
      adenosquamous cell carcinoma, 1 small cell carcinoma, 1 mucinous adenocarcinoma,
      1 adenoid cystic carcinoma, and 1 transitional cell carcinoma. CONCLUSION:
      Prostate cancer commonly develops in men over 65 years, and adenocarcinoma is the
      most common histological type. The disease has become a major malignant tumor to
      endanger elderly males.

PMID- 15999487
TI  - [Omission factors in detecting early stage prostate cancer by TRUS needle
      biopsy].
AB  - OBJECTIVE: To analyze and reduce the omission factors in detecting early stage
      prostate cancer by TRUS needle biopsy, and to improve the diagnosis of the
      disease. METHODS: A total of 80 benign prostatic hyperplasia patients suspected
      of prostatic carcinoma underwent TRUS sextant biopsies. The pathological results
      being negative, the patients received transurethral resection of the prostate
      (TURP). RESULTS: After TURP, 25 cases were pathologically diagnosed as prostate
      cancer, with an omission rate of 31.25% (25/80). Of the diagnosed cancer
      patients, 10 were treated by radical perineum prostatectomy, 8 by surgical
      castration, and 7 by medical castration. CONCLUSION: Some tumors may fail to be
      detected by TRUS needle biopsy. Serial or multi-core needle biopsies can decrease
      the omission rate in the diagnosis of organ confined cancer.

PMID- 15999488
TI  - [Experimental study on effects of testis murine cytomegalovirus infection on
      sperm viability in mice].
AB  - OBJECTIVE: To explore the effects of testis murine cytomegalovirus (MCMV)
      infection on mature sperm viability in mice. METHODS: BALB/c mice without MCMV
      infection, screened by ELISA, were randomly divided into two groups: an
      experimental group (n = 64) and a control group (n = 40). The former were
      directly inoculated with MCMV into the testis, while the latter treated by
      inoculation of DMEM without MCMV. The mice in both of the groups were sacrificed
      respectively at 1, 2, 4, 6, 9, 14, 21, 38 d postinoculation (D1, 2, 4, 6, 9, 14,
      21, 38 PI), the testis was examined histopathologically, and meanwhile the
      viability of mature sperms in the epididymis cauda was measured. RESULTS: MCMV
      basophil inclusion bodies were found in the Leydig cells in the experimental
      group, and spermatogenic cells were vacuolated and arranged disorderly. Compared
      with the control group, the sperm viability in the experimental group was
      decreased significantly by 71.42% to 56.04% (P < 0.05) on D1 PI. CONCLUSION: The
      sperm viability in mice might be descended significantly by MCMV infection in the
      early period, but restored to normal with time. This shows that MCMV infection
      might influence procreation transiently.

PMID- 15999489
TI  - [Health investigation of 3 551 middle-aged and old males in Jiangsu Province].
AB  - OBJECTIVE: To understand the state of health of the middle-aged and old males in
      Jiangsu Province. METHODS: A total number of 3 551 middle-aged and old males aged
      46 approximately 69 years were randomly selected from 13 counties of Jiangsu
      Province. All of them received physical examinations, including laboratory tests
      of liver and kidney function, sugar and cholesterols, radioimmunoassay of
      testosterone and free testosterone levels in the serum, and B-ultrasonic
      examination of the prostate volume and remaining urine. They also underwent
      inquiries according to the International Index of Erectile Function (IIEF-5) and
      the questionnaire for PADAM (partial androgen deficiency of the aging male).
      RESULTS: The prostate volume differed significantly (P < 0.05), while the
      testosterone level showed no significant difference in different age groups (P >
      0.05). The level of the free testosterone in the serum descended with the
      increase of age. The incidence of ED and PADAM was also correlated with the
      increase of age. CONCLUSION: In the old and middle-aged population of males, with
      the increase of age, sexual function decreases, the prostate volume enlarges, and
      the incidence of ED and PADAM obviously increases (P < 0.001).

PMID- 15999490
TI  - [Association between polymorphism of CYP17 gene and serum hormone concentrations
      in aged men].
AB  - OBJECTIVE: To investigate the association between polymorphism of CYP17 gene and
      serum hormone concentrations in aged men. METHODS: Eighty-three healthy men at
      the average age of 66.7 were divided into a < 66.7 group (n = 36) and a > 66.7
      group (n = 47), and the polymorphism of CYP17 gene in the 5' promoter region was
      investigated by PCR using DNA from the men's peripheral blood lymphocytes. A new
      recognition site was created for the restriction enzyme MspA1 I by transition (T 
      -> C) in the risk allele (A2). Three genotypes A1/A1, A1/A2, A2/A2 were
      established, serum sex-hormone levels measured, and mean hormone concentration
      evaluated in each genotype and age group. RESULTS: No evidence was found that the
      testosterone (T) level, estrogen (E2) level and T/E2 ratio were associated with
      the genotype of CYP17 gene. There was no significant difference in T and E2
      levels between the two groups, but there was a significant increase in the T/E2
      ratio (P < 0.05). CONCLUSION: A2 allele does not increase sex hormone levels in
      aged men, but the T/E, ratio was higher in the > 66.7 group than in the < 66.7
      group. This may be closely associated with the mechanism of benign prostate
      hyperplasia and prostate cancer in aged men.

PMID- 15999491
TI  - [Clinical analysis of 87 cases of testicular tumor].
AB  - OBJECTIVE: To improve the diagnosis and treatment of testicular tumor. METHODS:
      Eighty-seven cases of testicular tumor were retrospectively studied. RESULTS: Of
      the total number, 79 cases were pathologically diagnosed as germ cell tumor
      (90.1%), among which there were 44 cases of seminoma (55.7%) and 7 cases of
      benign tumor (8.1%). Nonseminoma germ cell tumor (NSGCT) was found mainly among
      those under 5 and from 18 to 40 years of age, while seminoma chiefly among those
      beyond 17, and testis tumor was rare among those between 5 and 17 years old (1
      case only). Three-year and 5-year survival rates of seminoma and NSGCT were 90.6%
      and 81.3%, and 83.3% and 56.7%, respectively. CONCLUSION: (1) Testicular tumors
      are mostly germ cell tumors. (2) NSGCT develops mainly among those under the age
      of 5 and from 18 to 40. (3) Seminoma is rare in those under 18. (4) Testicular
      tumor rarely develops among those between 5 and 17 years old. (5)Three-year and 5
      year survival rates for seminoma are higher than those for NSGCT.

PMID- 15999492
TI  - [P53 expression and its clinical significance in prostatic carcinoma].
AB  - OBJECTIVE: To investigate the expression of P53 protein and its clinical
      significance in prostatic carcinoma. METHODS: Formalin-fixed, paraffin-embedded
      tissue sections from 45 cases of prostatic carcinoma (PCa) and 10 cases of benign
      prostate hyperplasia (BPH) were analyzed retrospectively with immunohistochemical
      Elivision staining method. The relationship of P53 expression with prostate
      cancer stage, grade, PSA, endocrine therapeutic effect and prognosis was
      evaluated. RESULTS: The positive staining rates of p53 protein expression were
      51.1% and 10.0% respectively in patients with PCa and BPH (P < 0.05); 70.0% and
      25.0% in PCa patients at pathological stage D and stages A approximately C
      respectively (P < 0.05); 14.3% and 56.7% in those with Gleason score < or = 7 and
      > 7 (P < 0.05); 20.0% and 60.0% in those with PSA < or = 10 microg/L and PSA > 10
      micro/L (P > 0.05 ); 25.0% and 72.3% in those who responded to endocrine therapy
      and those who failed to respectively (P < 0.05). Log Rank analyses showed that
      the survival time of the PCa patients with negative P53 expression was obviously
      longer than those with the positive (P < 0.05 ). CONCLUSION: There were
      correlations between P53 expression and tumor grade, tumor stage and survival
      time, so the expression of P53 could be regarded as a prognostic molecular marker
      and a predictor of endocrine therapeutic effect for prostate cancer.

PMID- 15999493
TI  - [Long-term efficacy of TRUS-guided transperineal needle aspiration and irrigation
      on persistent hematospermia].
AB  - OBJECTIVE: To evaluate the long-term efficacy of transrectal ultrasonography
      (TRUS)-guided transperineal needle aspiration and irrigation for persistent
      hematospermia. METHODS: Included in the study were 12 patients with persistent
      hematospermia, aged (36.4 +/- 10.8) years, and with a course of the disease of
      (13.9 +/- 6.4) months. After the expressed prostatic secretion (EPS) by prostatic
      massage cultured, the patients received TRUS-guided transperineal needle
      aspiration for seminal vesicle fluid (SVF) for bacteriological examination. For
      the EPS positive patients, antibiotics were selected according to the drug
      sensitivity assay and injected into the abnormal seminal vesicle (SV) via TRUS
      guided transperineal needle puncture. The treatment was repeated one month later
      for those still with hematospermia. The patients were followed up every three
      months. RESULTS: Abnormal images were found in the SV and/or ejaculatory duct in
      9 cases, including SV and/or ejaculatory duct dilation, SV wall thickening,
      calcification or calculi of SV, and mullerian duct cyst. SVF cultures were
      positive in 7 cases, including 4 cases of methicillin-resistant Staphylococcus
      aurous (MRSA), 1 case of methicillin-resistant coagulase-negative staphylococcus
      (MRCNS), 1 case of E. Coli, and 1 case of Proteus mirabili. All the patients were
      treated by TRUS-guided transperineal injection of certain antibiotics into SV.
      Ten of them were followed up for (31.4 +/- 5.7) months. Hematospermia disappeared
      in 3 cases and relapsed at least once in the other 7. The last follow-up showed
      hematospermia recurrence in 2 cases. CONCLUSION: TRUS-guided transperineal
      irrigation of antibiotics into SV is effective to a certain extent for persistent
      hematospermia.

PMID- 15999494
TI  - [Diagnosis and treatment of urinary neurofibrosarcoma].
AB  - OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment
      of urinary neurofibrosarcoma. METHODS: Clinical data of 1 case of urinary
      neurofibrosarcoma was analyzed retrospectively and related literature reviewed.
      The 61-year old male patient had undergone TURP for benign prostate hyperplasia
      ten months before. RESULTS: Total urethral cavernostomy, total cystectomy and
      ileal cystostomy were performed on the patient and pathological diagnosis pointed
      to urinary neurofibrosarcoma. Another operation was done for metastatic rectal
      mass, which revealed abdominal metastasis. With progressing consumptive
      constitution, the patient died 40 days after the second operation. CONCLUSION: It
      is difficult to make a definite diagnosis in urinary neurofibrosarcoma, and the
      effective treatment for this highly malignant disease needs to be further
      studied.

PMID- 15999495
TI  - [Potassium ion channels and prostatic diseases].
AB  - Potassium ion channels are a complex of protein molded in the cell membrane
      lipids. Its expression is strong in normal prostatic epithelia and weak in
      different degrees in prostatic cancer epithelia, but not clearly known in chronic
      prostatitis epithelia. Drugs affecting potassium ion channels could provide a new
      direction and some new ideas for the treatment of prostatic diseases.

PMID- 15999496
TI  - [Advances in researches on the relationship between prostatic diseases and
      erectile dysfunction].
AB  - Prostatic diseases and erectile dysfunction (ED) are common diseases in urology
      and andrology. Basic and clinical studies have proved that there is a close
      relationship between the two. This article reviews the mechanism, diagnosis and
      treatment of ED caused by several prostatic diseases, such as acute prostatitis,
      chronic prostatitis, benign prostate hyperplasia and prostate cancer.

PMID- 15999497
TI  - [Partial androgen deficiency in the aging male apt to be misdiagnosed as
      depression and dementia: a typical case report].
AB  - A series of clinical symptoms associated with partial androgen deficiency in
      middle-aged and old males are apt to be confused with those of depression and
      dementia, and therefore result in misdiagnosis and mistreatment. This article
      reports a case of partial androgen deficiency in the aging male (PADAM)
      repeatedly misdiagnosed as depression and dementia, which demands sufficient
      clinical attention. The main reasons for the misdiagnosis and mistreatment lie in
      unfamiliarity with PADAM, lack of specific symptoms of the condition, omission of
      special examinations and hormone level analysis.

PMID- 15999498
TI  - [Advances in application of sildenafil to erectile dysfunction].
AB  - Since the worldwide introduction of sildenafil in 1998, 23 million patients with
      ED have been treated with the drug, and the accumulated experiences have proved
      its safety and efficacy. This article presents a review about the action
      mechanism and metabolic process of sildenafil, with a particular focus on the
      application of sildenafil to ED diagnosis, the curative effect of its daily use
      on ED, the standard treatment, combined therapy and progressive protocol with
      sildenafil for ED and its complications, along with such safety aspect as its
      effect on the sight.

PMID- 15999499
TI  - [Effects of food and alcohol on the pharmacokinetics of vardenafil].
AB  - There is a close relationship between sexual activity and meals or alcohol
      consumption. It is of great clinical significance for clinicians to understand
      the effects of food and alcohol on the pharmacokinetics of phosphodiesterase-5
      inhibitor vardenafil so as to give correct instructions to patients. Although a
      high-fat ( > 55% fat calories) meal modestly reduces C(max) by 18% and prolongs
      t(max) of vardenafil by approximately 1 hour, no significant effects of a typical
      moderate-fat meal (30% fat calories) on vardenafil pharmacokinetics were observed
      in a study carried out in 25 healthy adult males. So the adjustment of vardenafil
      dosage is not warranted based on a wide therapeutic index and the efficacy
      observed with vardenafil in Phase III studies, which need not be restricted with
      respect to food. In another study, the pharmacokinetics and safety profile of
      vardenafil were not affected if it was taken together with 0.5 g/kg ethanol. The
      above characteristics of vardenafil make the administration more convenient for
      patients.

PMID- 15999500
TI  - The media and the trauma service: friend or foe: part II--the interview.

PMID- 15999502
TI  - Human courage to endure.

PMID- 15999501
TI  - Spinal cord injury without radiographic abnormality (SCIWORA) in children.
AB  - SCIWORA is a syndrome occurring when the spinal cord sustains neural damage
      during a traumatic event without positive radiographic findings. Anatomic
      characteristics of the pediatric spine place children at risk for this injury.
      The injury occurs through extreme flexion, hyperextension, longitudinal
      distraction or ischemic damage to the spinal cord. Diagnosis is based on MRI
      findings. Timely diagnosis and stabilization is key to optimizing the child's
      recovery. Nursing care and evaluation of these children goes beyond the ABCs of
      resuscitation focusing on astute neurological examination.

PMID- 15999503
TI  - Reasons why trauma patients have missed injuries or delays in diagnosis.

PMID- 15999504
TI  - [More frequent radiation therapy in the treatment of head and neck tumors].

PMID- 15999505
TI  - [Intensive lipid lowering statin therapy immediately after acute coronary
      syndrome].

PMID- 15999506
TI  - [Serotonin medication does not increase the incidence of suicides].

PMID- 15999508
TI  - [Cutaneous cryosurgery].

PMID- 15999507
TI  - [Snake bites].

PMID- 15999509
TI  - [Evaluation of qualitative research].

PMID- 15999510
TI  - [Hypothyroidism of adult patients].

PMID- 15999511
TI  - [Upper extremity surgical reconstruction in patients with tetraplegia].

PMID- 15999512
TI  - [Perineal tear during vaginal birth].

PMID- 15999513
TI  - [Sudden sleepiness].

PMID- 15999515
TI  - [Crohn's disease].

PMID- 15999516
TI  - Smoking cessation: techniques and potential benefits.
AB  - Smokers have a significantly greater risk of complications during and after
      operations. Cigarette smoke has significant effects on cardiac function,
      circulation, and respiratory function. Preliminary studies suggest that smoking
      cessation for a minimum of 6 to 8 weeks before surgery is required to reduce the
      perioperative and postoperative risks of smoking. Smoking cessation programs that
      employ advice, support groups, nicotine replacement therapy, or some anti
      depressants have been used successfully in many situations and should be used to
      discourage smoking preoperatively. Further research is needed, however, to
      clarify the best approach to smoking cessation for surgical patients.

PMID- 15999517
TI  - Preoperative patient education in thoracic surgery.
AB  - Preoperative patient teaching may take many forms and is offered to patients
      across many venues and formats. The goal of patient teaching is to improve
      patients' understanding of their disease process and the operation that they are
      about to experience with the goal of enlisting their active participation in the
      healing process. The additional goal of obtaining informed consent is not only
      codified in law, but also has become an ingrained component to the current
      physician-patient relationship. The preoperative teaching process is best
      approached as a team effort, and multiple modalities often must be used so that
      the patient becomes a knowledgeable and willing member of the team.

PMID- 15999518
TI  - The value of preoperative pulmonary rehabilitation.
AB  - Although data are limited for preoperative pulmonary rehabilitation, benefit can
      be inferred largely from studies done on COPD and pulmonary rehabilitation
      because of the similarity of patient populations. Although underlying lung
      function is unchanged, patients who undergo preoperative pulmonary rehabilitation
      seem to experience an enhanced quality of life and increased functional capacity.
      Likewise, multidisciplinary rehabilitation programs can result in better patient
      compliance with medications and smoking cessation and decreased use of various
      health care resources. Although pulmonary rehabilitation works to benefit
      patients anticipating surgery, it also represents a valuable treatment
      alternative to patients who are poor surgical candidates. Pulmonary
      rehabilitation seems to be a cost-effective, benign intervention with no adverse
      effects and should remain an essential component of patient management before
      lung transplantation, LVRS, lung resection, and potentially any other elective
      thoracic surgical procedure.

PMID- 15999519
TI  - Informed consent: ethical and legal aspects.
AB  - The legal doctrine of informed consent looms large over the medical profession
      with many interest groups trying to expand and narrow the doctrine, including
      patient rights advocates, managed care organizations, government agencies, and
      accreditation organizations. The legal profession itself has taken no small part
      in defining the doctrine. No physician today is practicing without the daily
      influence of law on his or her practice of medicine. The doctrine of informed
      consent, with all of its ambiguities and difficulties, has established a medical
      duty on the physician to make a reasonable attempt to unite the goals of the
      patient and the physician. Ultimately, physicians gain from the knowledge that
      their wisdom and skill has fostered a decision that is amenable to the patient.
      The patient gains from a facilitated decision that truly reflects that
      individual's self-determined will. As a result, both parties enjoy a newly formed
      partnership and the return of something that has long been taken for granted-
      trust in the physician-patient relationship.

PMID- 15999520
TI  - Fast-tracking: eliminating roadblocks to successful early discharge.
AB  - With continually increasing health care costs and limited medical resources,
      there has been increasing focus on shortening hospital stays. Many medical and
      nonmedical reasons can lead to a delay in hospital discharge after thoracic
      surgery despite technically successful procedures; common obstacles include
      inadequate pain control, prolonged air leaks, and social issues. Preoperative
      patient education, minimally invasive surgical techniques, aggressive pain
      control, and early resumption of physical activity and discontinuation of chest
      tubes and catheters are important in successful early discharge. Although many of
      these components can be combined in clinical pathways to optimize care with the
      input of various members of the patient care team, the thoracic surgeon must
      reassess outcomes constantly to ensure the maintenance of the quality of care.

PMID- 15999521
TI  - Perioperative antibiotics: when, why?
AB  - The use of prophylactic antibiotics in general thoracic surgery is well
      established. This article explains the rationale for modern-day surgical wound
      infection prophylaxis, the why and the when. Various arguments about the use of
      antibiotics to prevent empyema and pneumonia after a thoracic operation also are
      presented.

PMID- 15999522
TI  - Pulmonary embolism prophylaxis: evidence for utility in thoracic surgery.
AB  - Patients requiring thoracotomy for the treatment of malignancy are at risk for
      developing a pulmonary embolism. Few data exist on effective prophylaxis
      techniques in this specific patient population, yet effective strategies can be
      inferred from other major surgical procedures to reduce the risk of this
      potentially life-threatening complication.

PMID- 15999523
TI  - Management of the anticoagulated patient.
AB  - Excessive bleeding or thrombosis is a preeminent concern for all surgeons.
      Patients may be at risk because of medical therapy, underlying disease, or
      complications related to both. An understanding of the coagulation cascade-
      mechanisms and tests of function--permits a rational, if not always complete,
      basis for a plan of therapy. Newer anticoagulation medications are changing how
      thrombotic complications, such a VTE or graft occlusion, are treated or
      prevented. This entire area is undergoing rapid evolution, and the approaches
      that have been standard for decades soon will be supplanted. Ultimately, however,
      the most important assessment is made at the bedside by the clinician.

PMID- 15999524
TI  - Preoperative cardiac evaluation: mechanisms, assessment, and reduction of risk.
AB  - The changing paradigm in cardiovascular disease in which atherosclerotic lesions
      exist in a spectrum of stable to unstable, the lack of a perfect prediction tool,
      and the paucity of randomized controlled data on appropriate intervention make
      protection of cardiac patients undergoing thoracic surgery challenging.
      Nociception-related sympathetic drive combines with inflammatory stimuli and the
      cardiodepressant effects of anesthesia to create a window of maximum risk in the
      early postoperative period (8-24 hours), and although multivariate models have
      shown that a combination of surgery-specific risk, patient-specific
      cardiovascular history, and estimated functional capacity best determine the need
      for further investigation, the optimal choice of investigation is unclear.
      Exercise or dobutamine stress echocardiography provide the best validated
      investigations, and in the case of poor images, dobutamine MR imaging is
      increasingly used. When disease is found, medical and interventional options are
      available. PCI is often used, but the risk of converting a stable flow-limiting
      lesion into a less stable non-flow-limiting lesion must be considered, along with
      a delay for anti-platelet therapy and endothelialization of the stent.
      Alternatively, medical protection with acute beta-blockade or alpha2-agonists
      reduces risk (although beta-blockade often is avoided in chronic lung disease,
      even nonselective agents are safe in patients with non-airways reactive COPD). In
      addition, it is likely that statin use reduces risk, probably by stabilizing
      plaques, but patients with cardiac risk are increasingly likely to be taking this
      medication already. The assessment and management of cardiac risk in the
      perioperative thoracic surgery patient is challenging. With focused, rational,
      and individually tailored management; tight monitoring of postoperative pain; and
      a close working relationship between the surgeon, anesthesiologist, and
      cardiologist, patient care can be optimized, and risk can be effectively
      controlled.

PMID- 15999525
TI  - Preoperative preparation for esophageal surgery.
AB  - Careful preoperative assessment is crucial in patients undergoing esophagectomy.
      The procedure carries significant morbidity and mortality, and careful evaluation
      is vital to minimizing risks. Tumor stage and the patient's general medical
      condition play equally important roles in determining operability. Patients with
      impaired pulmonary, cardiac, or nutritional function need to be identified, and
      reversible impairments need to be treated preoperatively. Preoperative tumor
      staging is done with a combination of tests, which should include CT, PET, and
      EUS for best noninvasive staging and more invasive techniques used on an
      individual basis.

PMID- 15999526
TI  - Preoperative preparation of the patient with myasthenia gravis.
AB  - All patients who are to undergo a thymectomy should be evaluated thoroughly by a
      neurologist--ideally one with special training and interest in the diagnosis and
      management of MG. Confirmatory tests to diagnose MG and other potential diseases
      should be reviewed. The antibody test seems to be most specific, but there are
      rare cases of other diseases that are ACh-R antibody positive. In 10% of MG
      patients, serology is negative, and other tests are necessary to confirm the
      diagnosis. All patients should undergo a contrast-enhanced high-resolution CT
      scan with 5- to 8-mm slices because thymoma or thymic carcinoma may be present.
      Pulmonary function tests, including vital capacity, forced expiratory volume,
      maximal expiratory force, arterial blood gas, and a flow-volume loop, should be
      performed. Exercise testing to evaluate for hypoxia and hypotension with exercise
      and ambulation also may be appropriate. A thorough assessment for cardiac
      dysfunction, including echocardiography, nuclear medicine studies, or a formal
      cardiology evaluation, may be beneficial. Because MG is a complex autoimmune
      disease, preoperative blood tests should include thyroid function testing,
      antinuclear antibody, and rheumatoid factor in addition to routine preoperative
      studies. Plasmapheresis or intravenous immunoglobulin should be considered for
      patients with advanced disease, bulbar symptoms, or poor pulmonary function.
      Given these guidelines, careful selection of candidates for surgery should
      optimize the long-term results for patients with MG.

PMID- 15999527
TI  - Preoperative pulmonary evaluation of the thoracic surgical patient.
AB  - Fig. 2 is an algorithm for the preoperative pulmonary evaluation of the lung
      resection candidate. Patients should undergo routine spirometry and diffusion
      capacity testing. If the FEV1 and DLCO are greater than 80% predicted, no further
      study is needed. When these parameters are less than 80%, some estimation of
      postoperative function is likely needed, taking into account the proposed
      resection. Patients with ppoFEV1 or ppoDLCO less than 40% are at increased risk
      of perioperative complications or death and should undergo formal exercise
      testing. A VO2max or ppoVO2max less than 10 mL/kg/min is associated with
      prohibitive risk for anatomic lung resection, and alternative treatment
      modalities should be considered.

PMID- 15999528
TI  - The preoperative anesthesia evaluation.
AB  - Thorough and timely anesthesia preoperative evaluation is essential for good
      patient outcomes. Perioperative care is becoming more complex and comprehensive,
      while older and sicker patients are being considered for major thoracic surgery.
      In addition to pulmonary and wound care, prevention of cardiac complications with
      beta-blocker therapy, multimodal pain control, tighter glycemic control,
      nutritional support, and prevention of thromboembolism are important
      perioperative goals. Early identification of significant medical and nonmedical
      issues allows for complete evaluation and planning and decreases the likelihood
      of delays, cancellations, and complications. Good communication and preparation
      benefit everyone. The implementation of an anesthesia preoperative assessment
      program or clinic can help achieve these important goals.

PMID- 15999529
TI  - siRNA is not more effective than a first generation antisense oligonucleotide
      when directed against EGFR in the treatment of PC-3 prostate cancer.
AB  - siRNA specifically directed against the epidermal growth factor receptor (EGFR)
      was compared to the previously described and effective MR2 oligo (also specific
      for EGFR) in a total of six comparative studies utilizing the chemotherapeutic
      agents Taxol, cisplatin and Cytoxan and the PC-3 prostate tumor line. When Taxol
      was administered in combination with either MR2 or siRNA, the MR2 was
      significantly more effective (p = 0.000277) against PC-3 cells incubated for 24 h
      in their presence. In a sequential study in which a 24-h Taxol treatment was
      followed with either MR2 or siRNA for an additional 24 h, or in the reverse order
      where MR2 or siRNA was followed by Taxol, no significant differences were found.
      When cisplatin was similarly administered in combination with either MR2 or the
      siRNA, no significant differences in inhibition were found. In a subsequent
      study, in which a 24-h treatment with either MR2 or siRNA was followed by
      cisplatin for an additional 24 h, again no significant differences were found.
      Lastly, in a series of sequential administrations including Cytoxan the following
      was found. PC-3 cells treated for 24 h with Cytoxan followed by either MR2 or
      siRNA produced similar inhibition. When the cycle was reversed, with MR2 or siRNA
      treatment followed by Cytoxan, both treatments were again inhibitory, however the
      initial treatment with MR2 was significantly more effective (p = 0.026095). We
      conclude that, although siRNA against EGFR has efficacy against the PC-3 line
      when administered either alone vs untreated controls, with Taxol vs Taxol alone,
      or with cisplatin vs cisplatin alone, it is not more effective than the better
      characterized MR2 oligo.

PMID- 15999530
TI  - Characterization of the ATPase activity of human ATP-binding cassette transporter
      2 (ABCA2).
AB  - BACKGROUND: ABCA2 is a member of the ATP binding cassette transporter family with
      functional roles in cholesterol homeostasis and drug resistance. MATERIALS AND
      METHODS: In order to characterize its ATPase activity, we transfected HEK293
      cells with an ABCA2 mammalian expression system and isolated ABCA2-enriched
      membranes. RESULTS: We found no measurable ATPase activity of ABCA2 in isolated
      membranes, except in the presence of the methyl-beta-cyclodextrin. However,
      competitive binding of a pseudo-substrate, 8-azido-[alpha-32P]-ATP, was
      demonstrated. CHO cells transfected with ABCA2 did not have a higher rate of
      endogenous ATP hydrolysis when compared to the mock-transfected cells.
      CONCLUSION: Overall, we conclude that, while ABCA2 may have low levels of ATPase
      activity that can be substrate-stimulated, it is more likely to have a regulatory
      role in cell physiology.

PMID- 15999531
TI  - Prevention of tumors of the large intestine by celecoxib in mice.
AB  - Celecoxib (C), a COX-2 enzyme inhibitor, was administered at a 0.1% dose level in
      the diet of female Swiss Webster CFW outbred mice for life. The mice also
      received 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as 10 weekly
      subcutaneous injections at 20 microg/g body weight. The number of animals with
      large intestinal cancer and the total number of these cancers were 30 and 321 in
      the 1,2-DMH-treated group, while the corresponding figures in the C and 1,2-DMH
      treated group were 29 and 156. This difference is statistically highly
      significant. The literature contains a limited number of publications concerning
      the cancer chemopreventive activity of C, particularly in mice. The present work,
      thus, provides additional proof in this field of interest.

PMID- 15999532
TI  - Phenotypic effects of calorie restriction and insulin-like growth factor-1
      treatment on body composition and bone mineral density of C57BL/6 mice:
      implications for cancer prevention.
AB  - BACKGROUND: Calorie restriction (CR) inhibits carcinogenesis and delays aging.
      Some anti-carcinogenic effects of CR are mediated by decreased circulating
      insulin-like growth factor-1 (IGF-1); however, IGF-1 also plays an important role
      in regulating growth and bone density. MATERIALS AND METHODS: We quantified
      tradeoffs involving the CR/IGF-1 axis in C57BL/6 mice by examining body
      composition and bone characteristics in ad libitum fed, 20, 30 or 40% CR mice
      that received placebo or recombinant murine IGF-1 delivered with a time-release
      pellet. After 26 days, carcasses were scanned with a PIXImus II dual-energy X-ray
      absorptiometer. RESULTS: CR reduced body weight and percent body fat and had non
      linear effects on bone density. IGF-1 restored bone density to control levels or
      greater in the CR mice. CONCLUSION: Cancer prevention efforts based on CR and
      down-regulation of the IGF-1 pathway will require consideration of deleterious
      effects on bone.

PMID- 15999533
TI  - Progressive degeneration of stereocilia in cochlear hair cells in hearing
      impaired kuru2 mice.
AB  - BACKGROUND: We previously isolated a mouse strain, kuru2, which exhibits abnormal
      behavior and hearing impairment. To investigate the etiology of this impairment,
      the ultrastructure of the inner ear was examined. MATERIALS AND METHODS: The
      morphologies of the cochlea and the vestibule of control (Jcl:ICR) and mutant
      mice were analyzed by electron microscopy. In some experiments, the mice were
      cross-mated and their offspring examined. RESULTS: The mutant mice displayed
      progressive degeneration of the stereocilia in the cochlea. The stereocilia
      started to degenerate on post-natal day 10 and, subsequently, the hair bundles
      continued to degenerate. On day 18, degeneration of the stereocilia was complete.
      In contrast, the vestibule was intact. DISCUSSION: Many mutant mice display
      hearing impairment These mice demonstrate a characteristic morphology of the
      inner ear and, since correlations may be made with corresponding human diseases,
      the current results could contribute to the further understanding of hearing
      impairment mechanisms.

PMID- 15999534
TI  - Induction of G0/G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix
      epithelial carcinoma (HeLa) cells.
AB  - The present studies were undertaken to analyze the factors regulating 3
      hydroxycinnamic acid-induced apoptosis and cell cycle arrest. Treatment of human
      cervix HeLa cells with 3-hydroxycinnamic acid induced apoptosis and G0/G1-phase
      arrest. The percentage of apoptosis induced by 3-hydroxycinnamic acid in HeLa
      cells was increased with incubation time. The results also demonstrated that 3
      hydroxycinnamic acid increased the expression of p53, caspase-3, Bax and cyclin
      B. These results demonstrated that 3-hydroxycinnamic acid induced apoptosis
      through p53- and caspase-3-dependent pathways.

PMID- 15999535
TI  - High grade cardiac lymphoma vitality monitoring by gadolinium-enhanced magnetic
      resonance imaging (MRI).
AB  - Primary cardiac lymphoma (PCL) is a rare disorder with a poor prognosis and
      response monitoring is often difficult. Delay in the diagnosis and infiltration
      of cardiac structures contribute to the unfavorable prognosis. We report on a 76
      year-old woman who was diagnosed as having an immunoblastic B-cell PCL according
      to a histology attained by catheter-guided biopsy. Systemic chemotherapy with six
      cycles of CHOP (Cyclophosphamide, Doxorubicine, Vincristine = Oncovine,
      Prednisone), combined with the monoclonal anti-CD20 antibody Rituximab induced
      only a partial remission, based solely on monitoring of tumor size. However,
      cardiac gadolinium-enhanced magnetic resonance imaging (CMR) disclosed a reduced
      lymphoma perfusion and, therefore, indicated decreased tumor vitality. Nine
      months after the final treatment, the cardiac tumor further decreased to 10% of
      the initial size, and the patient is in sustained remission as monitored by CMR
      and validated by florine-18 fluorodeoxyglucose positron emission tomography
      (PET). Determination of PCL perfusion was, in our case, beneficial for clinical
      decision making on additional therapy.

PMID- 15999536
TI  - The role of hepatic stimulator substance (HSS) on liver regeneration arrest
      induced by cadmium.
AB  - BACKGROUND: The mechanism of cadmium-induced liver regeneration arrest in
      relation to hepatic stimulator substance (HSS) biological activity was
      investigated. MATERIALS AND METHODS: In Wistar rats subjected to 65 - 70% partial
      hepatectomy, saline, cadmium, cadmium and HSS were administered. The rats were
      also subjected to 30 - 34% partial hepatectomy. Mitotic index, immunochemistry
      for PCNA, 3[H]-thymidine incorporation into DNA and thymidine kinase activity
      were used as indices of liver regeneration. HSS biological activity was evaluated
      in all groups of rats using a bioassay. RESULTS: Liver regeneration and HSS
      activity were arrested by cadmium during the first 24 h after partial
      hepatectomy. Both in normal and in cadmium-treated rats, the HSS activity was
      increased and liver regeneration coincided. HSS activity was stable in 30 - 34%
      hepatectomized rats. HSS administration was able to restore liver regeneration
      arrest induced by cadmium. CONCLUSION: The biological activity of HSS increased
      at the time of G1/S transition of hepatocytes in the cell cycle and no increase
      was observed with asynchronous G1/S transition (30 - 34% partial hepatectomy).
      The suppression of HSS biological activity by cadmium seems to represent an
      important factor for liver regeneration arrest induced by the metal and HSS
      administration is able to restore liver regeneration.

PMID- 15999537
TI  - Coumarin derivatives with tumor-specific cytotoxicity and multidrug resistance
      reversal activity.
AB  - A preliminary exploration of coumarin derivatives as novel multidrug resistance
      (MDR) modulators was carried out to determine the basic features of the structure
      responsible for the MDR reversal activity. Among 44 coumarins, 14 compounds
      moderately induced the reversal of MDR (fluorescence activity ratio (FAR) values
      > 1). The most active compound, 6-hydroxy-3-(2-hydroxyethyl)-4-methyl- 7
      methoxycoumarin [C34], was equally potent as a MDR modulator verapamil. These
      data show a relationship between the chemical structure and MDR-reversal effect
      on tumor cells. All coumarins tested were more cytotoxic against tumor cells than
      normal cells. Several compounds displayed potent cytotoxic activities (CC50 15 -
      29 microg/mL in HSC cells), comparable with that of gallic acid (CC50 = 24
      microg/mL). Both 6-hydroxy- 7-methoxy-4-methyl-3-isopropylcoumarin [C43] and 3
      ethyl-6-hydroxy- 7-methoxy-4-methylcoumarin [C44] showed the highest tumor
      specific cytotoxicity (SI value = 4.1 and 3.6, respectively). We conclude that
      coumarins are potentially potent new MDR modulators with low toxicity against
      normal cells. A deeper understanding of the relationship between their structures
      and their potency will contribute to the design of optimal agents.

PMID- 15999538
TI  - Palliative radiotherapy with electrons of appendicular osteosarcoma in 54 dogs.
AB  - Radiotherapy is effective for the palliation of pain associated with primary and
      metastatic bony neoplasia in dogs and humans, but no standard treatment protocol
      has been established. The goal of this study was to evaluate a 3 x 8 Gy and a 4 x
      6 Gy protocol using electrons with a betatron or linear accelerator for the
      treatment of appendicular osteosarcoma in 54 dogs. Thirty-three dogs received
      chemotherapy consisting of carboplatin IV concurrently with radiotherapy. Eighty
      three % (n = 45) of the dogs experienced pain relief during or following
      treatment. The median duration of pain relief from treatment start was 53 days.
      In conclusion, both protocols are effective for palliation of clinical signs of
      canine appendicular osteosarcoma. The outcome reported here is similar to the
      results of other studies using Co photons. The use of chemotherapy did not
      improve the response to radiotherapy.

PMID- 15999539
TI  - Determinants of cisplatin and irinotecan activities in human lung adenocarcinoma
      cells: evidence of cisplatin accumulation and topoisomerase I activity.
AB  - To elucidate the sensitivity of adenocarcinoma of the lung to cisplatin and
      irinotecan, intracellular glutathione (GSH) and glutathione S-transferase (GST)
      pi concentrations and topoisomerase (topo) I activity were investigated using six
      adenocarcinoma cell lines. The antiproliferative activity was determined by MTT
      assay in terms of inhibition concentration (IC50) values. The IC50 values to
      cisplatin were not correlated with the amounts of intracellular GSH or GST-pi,
      but with intracellular accumulation of platinum (r = -0.91, p = 0.013). IC50
      values to SN-38 were correlated with topo I activity determined by relaxation
      assay of pBR322 (r = -0.83, p = 0.040). These results suggest that platinum
      accumulation and topo I activity have definite impacts on the sensitivity of lung
      adenocarcinoma to cisplatin and irinotecan, respectively.

PMID- 15999540
TI  - Search for a genetic link for mammary cancer in a beagle colony.
AB  - BACKGROUND: A possible genetic link for malignant mammary tumor (MMT) was
      investigated. MATERIALS AND METHODS: Records of an internally-irradiated beagle
      colony followed from the early 1950's until about 1995 were searched and analyzed
      by standard statistical procedures. RESULTS: Only a single ancestor yielded a "p"
      value (Fisher's Exact Test) for an overrepresentation among descendants with MMT
      at < 0.025 (one-sided test), and the number of comparisons for the 169 ancestors
      where the relative fraction of animals with MMT was greater than that for non MMT
      dogs (61) suggests that this could have occurred by chance alone. Results of
      other statistical tests were not remarkable. CONCLUSION: No genetic link for MMT
      in this colony could be established with the available data. These findings may
      or may not be relevant to humans.

PMID- 15999541
TI  - Prevalence of human herpesvirus 8 DNA sequences in human immunodeficiency virus
      negative individuals without Kaposi's sarcoma in Greece.
AB  - BACKGROUND: It has already been established that the prevalence of human herpes
      virus 8 (HHV8) in the general population varies among different geographical
      areas. The objective of this study was to evaluate the prevalence of HHV8
      infection in the Greek population. MATERIALS AND METHODS: Eight hundred blood
      samples were collected consecutively from human immunodeficiency virus (HIV)
      negative individuals without evidence of Kaposi's sarcoma (KS). All individuals
      were Greeks and were classified according to gender, age and geographic origin.
      HHV8 DNA sequences were detected by nested-PCR. RESULTS: An overall HHV8
      positivity rate of 9.6% was found. Analysis of the KS330 region within ORF-26
      revealed that the HHV8 strains were distributed to the C1, C3 or A1 subtypes.
      Logistic regression showed no association between HHV8 presence and geographic
      regions in Greece. The results indicate that very few individuals (4.3%) were
      exposed to HHV8 before 15 years of age. The infection rate peaked (16.4%) between
      the ages of 31 and 40. Females and males showed similar prevalence of HHV8.
      CONCLUSION: The data suggest that HHV8 is spread in Greece, but to a lesser
      extent than that observed in other Mediterranean countries. The fact that HHV8
      was also found in individuals under 15 years of age indicates that a small
      percent of HHV8 transmission could occur through non-sexual contacts.

PMID- 15999542
TI  - The in vitro activity of phenothiazines against Mycobacterium avium: potential of
      thioridazine for therapy of the co-infected AIDS patient.
AB  - Patients presenting with Acquired Immune Deficiency Syndrome (AIDS) are
      predisposed to co-infection with Mycobacterium avium. The management of such
      patients is problematic due to underlying immuno-incompetence and the high
      resistance of M. avium to most non-toxic compounds. Therefore, the need for
      effective agents is obvious. Because phenothiazines, especially the relatively
      mild thioridazine, have significant activity against Mycobacterium tuberculosis,
      we investigated the in vitro activity of chlorpromazine, thioridazine, promazine,
      promethazine and desipramine against a reference and clinical strains of M.
      avium. The results obtained show that whereas all of the phenothiazines employed
      in this study had an minimum inhibitory concentration (MIC) against the strains
      studied that ranged from ca. 10 to > 50 mg/L, as was previously shown for M.
      tuberculosis, thioridazine was the most active of the group against M. avium.

PMID- 15999543
TI  - Detection of HCV in bile duct epithelium by laser capture microdissection (LCM).
AB  - Chronic hepatitis C affects 0.3 to 1.5% of the general population worldwide. The
      estimated total number of newly acquired hepatitis C virus (HCV) infections is
      28,000 in the USA, with 10,000 deaths each year resulting from HCV-associated
      chronic liver disease. Histological examination of liver tissue from chronic HCV
      infection shows lymphoid aggregates or follicles in the portal triads, focal
      fatty change and lobular inflammation. Hepatitis-associated bile duct lesion
      (HBL) is seen in 5 - 91% of the cases. While the morphological spectrum of HBL
      has been well described, its pathogenesis in hepatitis C is not known. To this
      date, evidence supports both the direct injury and immune-mediated mechanisms,
      but to what extent these mechanisms are involved in the pathogenesis of HBL in
      chronic hepatitis C remains unclear. Our study showed the presence of HCV in the
      bile duct epithelium of patients with chronic hepatitis C infection, using the
      laser capture microdissection technique. These results will enhance our
      diagnostic capabilities and treatment of chronic hepatitis C infection.

PMID- 15999544
TI  - Assessment of antioxidant / anticarcinogenic activity of plant extracts by a
      combination of molecular methods.
AB  - Cancer chemoprevention is considered to be a promising approach for cancer
      control, as it has been identified by both epidemiological and molecular studies
      that environmental factors are the major causes of cancer. Chemoprevention can be
      defined as the use of agents to prevent, inhibit or reverse the process of
      carcinogenesis. Several epidemiological studies have shown that fruits,
      vegetables and common beverages, as well as herbs and plants, are rich sources of
      chemopreventive compounds. In the present report, a battery of in vitro methods
      for the identification of chemopreventive agents are presented. These methods
      include: i) inhibition of bleomycin-induced mutations in Salmonella typhimurium
      TA102 cells, ii) inhibition of bleomycin-induced sister chromatid exchanges
      (SCEs) in human peripheral blood lymphocytes, iii) protection from mitomycin C
      induced DNA strand breakage and iv) inhibition of topoisomerase I DNA relaxation.
      The first three methods are also used for the identification of agents which
      prevent reactive oxygen species (ROS)-mediated DNA damage.

PMID- 15999545
TI  - Immunocytochemical detection of members of the caspase cascade of apoptosis in
      childhood medulloblastomas.
AB  - During the process of programmed cell death (PCD), the cell disintegrates into
      small, membrane-bound apoptotic bodies. Caspase-3 is ubiquitously expressed in
      normal and neoplastically-transformed human cells and serves as an executioner in
      the apoptotic or PCD pathway. During our immunocytochemical study, a sensitive,
      four-step, alkaline phosphatase-conjugated antigen detection technique was
      employed. The results demonstrated the presence of apoptotic activity within the
      cellular microenvironment of childhood medulloblastoma/primitive neuroectodermal
      tumor. The observations identified the cytoplasmic presence of caspase-3 in more
      than 20% of neoplastic cells. The immunocytochemical expression pattern
      demonstrated a translocation tendency from the cytoplasm to the cell nuclei in
      the apoptotic cells in about 5% of the tumor cells. Caspase-3 presence was also
      detected in the tumor infiltrating lymphocytes (TILs), representing the host's
      immune, mostly CD8+, cytotoxic, tumor-associated antigen (TAA)-directed effector
      cells. This phenomenon may play an important role in these tumors' maintenance of
      immune privilege and evasion of immune attacks. We suggest that the grade and
      intensity of apoptosis may not only have diagnostic and prognostic significance,
      but could also play a leading role in the biological (fourth modality)
      antineoplastic treatment of these highly malignant, neuroectodermal brain tumors.

PMID- 15999546
TI  - Macroscopical and histopathological changes in regressing primary and recurrent
      equine sarcoids during active specific bio-immunotherapy.
AB  - Healing sarcoids were followed in 18 horses which had taken part in previous
      clinical studies on a total of 29 horses suffering from either primary or
      recurrent sarcoids, treated with bio-immunotherapy. In the present study,
      attention was paid to changes observed in these fibroblastic skin tumours during
      their regression. The tumours were surgically debulked leaving the base in the
      skin. The horses were immunized according to bio-immunotherapy at 2- to 4-week
      intervals with an autogenous vaccine made from the excised part of the tumour
      until the base had visibly regressed. Healing was followed by inspections and
      serial biopsies from the base, studied under light microscope. Visibly normal
      epithelisation developed first at the margin of the base, progressing gradually
      to the centre. The mean rate of epithelisation was approximately equal to normal
      horse skin. Most of the histopathological features typical of equine sarcoid
      diminished significantly in the follow-up biopsies, when the first signs of
      visibly normal epithelisation were observed. The changes were more evident among
      the primary than the recurrent tumours. No leucocyte infiltration, lysis or
      apoptosis were found during the regression. Bio-immunotherapy seems to simulate a
      spontaneous healing process.

PMID- 15999547
TI  - Expression of cytokeratins 8 and 18 on Mallory body and oval cell in rats during
      hepatic fibrosis.
AB  - BACKGROUND: The aim of this study was to determine the induction and distribution
      of Mallory body (MB) and oval cells in carbon-tetrachloride (CCl4)-induced rat
      liver fibrosis. MATERIALS AND METHODS: MBs and oval cells expressing cytokeratins
      (CKs) 8 and 18 were monitored by immuno-histochemistry and immunoblotting.
      RESULTS: MBs were mainly detected within hepatocytes near the fibrotic areas, and
      oval cells were located along or in the fibrotic areas. Both MBs and oval cells
      increased in size and number in the development of fibrosis. At cirrhotic liver,
      most of the oval cells were located in the fibrous septa and around newly formed
      bile ductules. Moreover, as hepatic injuries developed into fibrosis, a much more
      prominent single band of CK18 was detected. CONCLUSION: The occurrence and
      distribution of MB and oval cells in CCl4-induced rat liver fibrosis are
      reported. This represents the first CCl4 experimental in vivo model of MB
      induction, which will be useful for further investigations on the pathogenesis of
      MB.

PMID- 15999548
TI  - A rare case of solitary fibrous tumour of the pre-sacral space: morphological and
      immunohistochemical features.
AB  - A 28-year-old woman presented with abdominal pain. Ultrasonograhic examination
      showed a pre-sacral mass, with complex structure and well delimitated cystss with
      thick walls. The resected specimen was 7.5 x 6 x 4 cm in size, well circumscribed
      and yellow in colour, with cysstic change containing mucoid-like material.
      Histologically, the lesion was composed of spindle cells with high cellularity
      and rich vascularization with a haemangiopericytoma-like pattern. The diagnosis
      of solitary fibrous tumour (SFT) was made. The differential diagnosis for SFT of
      the pre-sacral spaace involves haemangiopericytoma, GIST, malignant mesothelioma,
      synovial sarcoma, leiomyomatous tumours and granulosa cell tumour.
      Immunohistochemical studies revealed reactivity for CD34, CD99 and Bcl-2, but no
      staining for desmin, inhibin, c-kit, EMA, CK, SMA, S-100 and CD31, confirming a
      diagnosis of SFT. Although SFT is usually associated with a favourable prognosis,
      close follow-up is recommended because of the limited information on its long
      term behaviour.

PMID- 15999549
TI  - Comparison of the effect of 99mTc-DPD and 99mTc-MDP on experimentally-induced
      osteoarthritis in the stifle joint of the dog.
AB  - This study was designed to evaluate the effect of 99mTechnetium-dicarboxypropane
      diphosphonate (99mTc-DPD) and 99mTechnetium-methylene diphosphonate (99mTc-MDP)
      on bone scan image quality and time in dogs with osteoarthritis. The left cranial
      cruciate ligament (CrCL) in ten healthy adult Beagle dogs was transected under
      general anesthesia. The dogs were assigned to 99mTc-DPD-injected or 99mTc-MDP
      injected groups. Stifle joint scintigraphy was performed after intravenous
      injection of 10 mCi 99mTc-DPD or 99mTe-MDP. Scintigraphy was conducted before
      CrCL transection and 2, 4, 6, 8, 10 and 12 weeks after the procedure. There were
      no significant differences in density, sensitivity and pathological foci between
      the 99mTc-DPD and 99mTc-MDP groups of experimentally-transected CrCL dogs. A
      comparison of the images obtained with Pinhole type and low energy general
      purpose type collimators of the stifle joint of normal dogs and after CrCL
      transaction revealed no significant differences in bone radioactivity.
      Scintigraphs were obtained 3 h after 99mTc-MDP and 2 h after 99mTc-DPD injection.
      In conclusion, application of 99mTc-DPD and 99mTc-MDP in experimentally-induced
      osteoarthritis of the stifle joint in dogs results in similar effects on
      radioactive uptake ratio and image quality. 99mTc-DPD is more efficient than
      99mTc-MDP in reducing the overall time of scintigraphy.

PMID- 15999550
TI  - Administration of estramustine in response to changes in the prostate-specific
      antigen and Karnofsky index in the treatment of prostate cancer.
AB  - Androgen ablation is palliative and does not cure advanced prostate cancer. The
      hormone-sensitive cells die and the hormone-resistant cells overgrow, resulting
      in disease progression. The drug of choice for secondary treatment is
      estramustine (Estracyt). The success of the therapy is followed by changes of the
      prostate-specific antigen level and Karnofsky scale. In the present study, the
      results of estramustine treatment of 79 patients with advanced prostate cancer in
      12 hospitals were evaluated. The mean prostate-specific antigen level improved
      for 6 months, but rose from the ninth month on. The improvement in the subjective
      condition of the patients paralleled the change in the prostate-specific antigen
      level. The short time of improvement was a consequence of the very high prostate
      specific antigen level and the poor general condition. Estramustine
      administration is recommended when the prostate-specific antigen level becomes
      more than doubled following primary treatment. At a starting prostate-specific
      antigen level of > 100 ng/ml, the treatment leads to total androgen blockade. If
      the prostate-specific antigen level has not decreased after treatment for 3
      months, the secondary strategy is to apply chemotherapy.

PMID- 15999551
TI  - Potential prognostic value of circulating levels of vascular endothelial growth
      factor-A in patients with gastric cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the potential prognostic value
      of the circulating levels of vascular endothelial growth factor-A (VEGF-A) in
      patients with gastric cancer. MATERIALS AND METHODS: An ELISA was used to
      quantify the serum and plasma levels of VEGF-A in 135 patients with gastric
      cancer and 48 controls with benign gastric diseases diagnosed by gastroendoscopy
      and histology of the biopsied specimens. Serum VEGF-A levels were assayed in
      controls (n = 10) and patients with gastric cancer (n = 10) prior to surgery.
      Further samples from 16 patients with gastric cancer, 3 weeks after tumour
      excision, were collected. RESULTS: VEGF-A levels were significantly higher in
      both serum and plasma from patients with gastric cancer than those from the
      controls (serum: 342.1 pg/ml vs. 80.0 pg/ml, p < 0.01; plasma: 74.1 pg/ml vs.
      23.7pg/ml, p < 0.01). In both cancer patients prior to surgery and controls,
      serum VEGF-A levels appeared to be unchanged over a 7-day period. However,
      examination of paired samples from 16 cancer patients collected prior to surgery
      and 3 weeks post-surgery showed that tumor excision resulted in a significant
      decrease in VEGF-A levels (Paired t-test, t = 5.4, p < 0.0001). CONCLUSION: Serum
      and plasma VEGF-A levels were significantly higher in patients with gastric
      cancer than in the controls. Serum VEGF-A levels correlated with tumour burden,
      as VEGF-A levels were significantly lowered following tumour excision in patients
      with gastric cancer.

PMID- 15999552
TI  - Correlation of MDR 1 expression and CA 125 in ovarian cancer.
AB  - BACKGROUND: The serum CA 125 marker is elevated in 80% of patients with ovarian
      adenocarcinoma. MDR 1 gene expression has been identified in a variety of tumor
      types and its expression has been correlated with multidrug resistance. Whether
      there is a correlation between CA 125 levels and MDR 1 expression has not been
      sufficiently investigated. Therefore, the aim of this study was to examine
      whether an association between serum CA 125 levels and MDR 1 expression exists.
      PATIENTS AND METHODS: Serum CA 125 levels were measured during the diagnosis of
      ovarian cancer. Fresh tumor specimens or ascitic fluid samples were studied for
      MDR 1 expression by the polymerase chain reaction method (PCR). RESULTS: Forty
      patients with ovarian cancer were studied, 34 (85%) of whom had elevated CA 125.
      Twenty-eight out of the 40 patients were tested for MDR 1 expression; 20
      expressed the gene and 8 did not. The median level of CA 125 in specimens
      expressing the MDR1 gene was 327, and in specimens that did not it was 376. There
      was no correlation between the CA 125 levels and MDR 1 expression (p = 0.484).
      CONCLUSION: There does not seem to be an association between CA 125 levels and
      expression of the MDR1 gene in patients with ovarian cancer.

PMID- 15999553
TI  - Inhibitory effect of whole bee venom in adjuvant-induced arthritis.
AB  - The aim of this study was to assess the inhibitory effect of whole bee venom (BV)
      on adjuvant-induced arthritis in the rat. Rats were divided into pre-apitherapy,
      post-apitherapy and control experimental groups. The pre-apitherapy group was
      subcutaneously stung with a honeybee (Apis mellifera L.) and the control group
      was subcutaneously injected with 0.1 ml of physiological saline solution one day
      prior to complete Freund's adjuvant (CFA) injection. The post-apitherapy group
      was subcutaneously stung with a honeybee on day 14 after CFA injection. When
      arthritis had developed in the rat, the post-apitherapy group was subcutaneously
      administered whole BV every other day for a further 14 days. Clinical signs,
      hematological values and radioglogical features were observed during the entire
      experimental period. In the pre-apitherapy group, the development of inflammatory
      edema and polyarthritis was inhibited. Significant differences in lameness score,
      hind paw edema volume and radiological features were observed between control and
      pre-apitherapy rats. White blood cell counts indicated that the degree of
      leucocytosis was significantly different between the pre-apitherapy and control
      groups (p < 0.01). Inflammatory edema, polyarthritis and bone change into the
      right hind paw were effectively inhibited in pre-apitherapy rats during the two
      week period post-CFA injection. In conclusion, whole BV was found to inhibit
      arthritic inflammation and bone changes in the rat. This may be an alternative
      treatment for arthritis in humans.

PMID- 15999554
TI  - [Lag Ba-Omer bonfires--is there any association between the tradition and asthma
      and COPD exacerbations].
AB  - BACKGROUND: Air pollution is a potential cause of asthma and COPD exacerbations.
      On the evening of Lag Ba-Omer, when there were bonfire parties throughout the
      country, significant air pollution was reported. OBJECTIVES: To evaluate the
      association of the air pollution caused by Lag Ba-Omer bonfires party (8th May
      2004) and asthma and COPD exacerbations in the Rehovot area. METHODS: Data on air
      quality and pollution levels was retrieved from the monitoring system of the
      Ministry of the Environment for the period of Lag Ba-Omer (May 2004). All visits
      to the Kaplan Medical Center Emergency Department, local after-hours first aid
      clinics and hospital admissions in May 2004 were evaluated. The daily rate of
      visits and admissions with the diagnosis of asthma or COPD exacerbation was
      recorded. RESULTS: Data from the Rehovot monitoring station revealed worsening in
      the air pollution indices in the two days after Lag Ba-Omer. On the same days of
      the week, a week earlier and a week later, the air quality was good. There was no
      increase in asthma or COPD visits to after-hours first aid clinics and no
      increase in hospitalizations. An increase in the rate of visits due to asthma and
      COPD to the emergency department was noted in the days after Lag Ba-Omer in
      comparison to the control days (15/277 (5.4%) vs. 14/593 (2.4%), p < 0.05).
      CONCLUSION: There was an increase in emergency department visits due to asthma
      and COPD without an increase in hospital admissions in the days of air pollution
      after Lag Ba-Omer. Further studies should focus on a possible increase in self
      medication and family physician visits in the period around Lag Ba-Omer.

PMID- 15999555
TI  - [Episiotomy as a risk factor for early perineal trauma].
AB  - OBJECTIVE: To assess the association between medio-lateral episiotomy and early
      perineal trauma. STUDY DESIGN: A prospective observational cohort study of 667
      consecutive vaginal deliveries was conducted over a 10-week period. On the day
      following delivery, all women were examined for the extent of early perineal
      trauma (swelling, oedema, haematoma), in addition to the episiotomy or
      lacerations. The demographic and clinical variables (age, parity, gestational
      age, birthweight, length of second stage, operative delivery, epidural, seniority
      of the obstetrical provider, episiotomy) and the post-partum treatment given for
      the perineum were retrieved from the hospital records. RESULTS: The overall
      episiotomy rate was 37.6%. Significant early perineal trauma was found in 9.9% of
      the women, more so in the episiotomy group (17.1% vs 5.5%, p < 0.001). In the
      episiotomy group, a larger number of women received more than routine treatment
      for the perineum (6.4% vs 2.9%, p < 0.05). Episiotomy was found to be the major
      independent predictor for perineal trauma (OR: 4.5, 95% CI: 2.4-8.5, p < 0.001),
      followed by epidural analgesia (OR: 2.4, CI: 1.3-4.3, p < 0.05) and birth weight
      >3700 g (OR: 2.1, CI: 1.1-4.1, p < 0.05). CONCLUSION: Episiotomy does not prevent
      immediate postpartum perineal trauma; rather, it is a major independent risk
      factor associated with significant early perineal trauma.

PMID- 15999556
TI  - [Fournier's gangrene as a delayed complication of closed hemorrhoidectomy].
AB  - BACKGROUND: Fournier's gangrene is recognized as a synergistic necrotizing
      fasciitis of the perineum and abdominal wall along with the scrotum and penis in
      men and the vulva in women. The major sources of Fournier's Gangrene are
      dermatologic, anorectal and genitourinary infections. Although anorectum is
      remarkably rich in bacterial flora, transanal procedures are generally free of
      infectious or septic complications. Nevertheless, five cases of Fournier's
      gangrene post hemorrhoidectomy have been published. OBJECTIVE: To report a case
      of Fournier's gangrene as a delayed complication of closed hemorrhoidectomy and
      to demonstrate the management of such complication. PATIENT: A sixty-six years
      old male who had undergone an uncomplicated closed hemorrhoidectomy was
      readmitted to the hospital on postoperative day 7 for fever, perirectal erythema
      and tenderness accompanied by a dirty brown discharge from the wound. The patient
      was treated with fluid resuscitation and broad-spectrum antibiotics. Radical
      debridement of the perianal and scrotal region was performed accompanied by
      diverting colostomy. Four months later a reconstruction of the perianal area was
      performed by meshed split thickness skin graft and the colostomy was closed.
      CONCLUSIONS: Fournier's gangrene is a rare immediate or delayed complication of
      hemorrhoidectomy. A review of the limited available literature suggests that
      neither the surgical technique nor the medical history of the patient have an
      influence on the development of such a rare and fatal complication.

PMID- 15999557
TI  - [Should a minor, unattended by a parent, be given medical services? Use of an
      algorithm to critique the Israel Ministry of Health regulations].
AB  - BACKGROUND: Parents are the natural custodians of their children, thus minors
      need parental approval to receive medical services. In February 2004, the Israel
      Ministry of Health issued a set of regulations titled "Visits of unaccompanied
      minors to primary care clinics", aimed at assisting primary care clinicians in
      their decision-making process on this sensitive issue. AIMS: (1) To convert the
      above mentioned regulations into an algorithmic format in order to facilitate
      their use by community clinicians, and (2) To review and critique the
      regulations, using the process of algorithm conversion. METHODS: The regulations
      were studied thoroughly. Three rounds of Delphi process for reaching consensus
      were used to create an algorithm, based on these regulations. The algorithm
      building process was used to critique the regulations. RESULTS: The Israel
      Ministry of Health regulations, "Visits of unaccompanied minors to primary care
      clinics", were found to be long and complicated. The process of building the
      algorithm revealed several difficulties certain concepts were not well defined,
      many exceptional situations were found and a large portion of the regulations was
      dedicated to reporting and record keeping. Converting the regulations into an
      algorithmic format simplified them and assisted in their CONCLUSIONS: Converting
      complex regulations into an algorithmic format can facilitate their daily use by
      community clinicians. Parts of the regulations for "Visits of unaccompanied
      minors to primary care clinics" are incompatible with present clinic routine and,
      therefore, difficult to implement.

PMID- 15999558
TI  - [Mother's education and ethnicity effect on health measures for children in the
      Haifa subdistrict].
AB  - OBJECTIVE: This study aimed to assess the association between the health markers
      of vaccination coverage, birth weight, hemoglobin levels and nutritional status
      with the ethnic origin and the mother's educational status among all infants born
      in 1995 and toddlers born in 1994 in the Haifa subdistrict. METHODS: The data on
      vaccination coverage rates and other different measures was collected from the
      Mother and Child Health (MCH) centers in the Haifa subdistrict. MCH centers were
      categorized into 4 levels of mother educational status (MES) using the
      distribution of the average number of years of schooling of the registered
      children's mothers. RESULTS: (1) More than half of the Arab sector in this study
      were classified in the lowest level of MES, while only 3% of the Jewish sector in
      this study were classified in this level. (2) No significant association between
      vaccine coverage rate and MES or ethnicity was found. (3) The percentage of low
      birth weight was higher among Jews. (4) No consistent association between birth
      weight and MES. (5) The rate of children with anemia was higher in Arabs (18%)
      than in Jews (10%). (6) No significant association between anemia and MES in both
      sectors. CONCLUSIONS: Differences in health measures were found to be associated
      with ethnicity but not with mother educational status. Arabs were found to be at
      higher risk for anemia and probable improper nutrition habits than Jews. Thus
      appropriate health promotion programs should be targeted towards this group,
      especially programs to improve the hemoglobin levels.

PMID- 15999559
TI  - [Education level and origin as predictors of hospitalization among Jewish adults
      in Israel: a population-based study].
AB  - BACKGROUND: Age, sex, origin and level of education are recognized as predictors
      of healthcare utilization. However, the joint effects of these variables on the
      risk of hospitalization have yet to be described for specific diagnostic
      categories, such as diseases of the circulatory, respiratory, genitourinary,
      digestive and nervous systems, infectious and parasitic diseases, malignant
      neoplasms, injury and poisoning. OBJECTIVES: To evaluate the association between
      origin, education, sex, age and the risk of hospitalization due to major
      diagnostic categories. METHODS: Cross-sectional study linking population-based
      databases, including Israeli census and hospitalization records. RESULTS: The
      study encompassed 35,413 hospitalized subjects and 386,317 non-hospitalized
      subjects. Origin other than Israel was a risk factor for hospitalization, with an
      odds ratio of 1.31 (95% CI 1.25-1.36) for Asia, 1.43 (1.37-1.50) for Africa, and
      1.24 (1.20-1.29) for Europe-America (P for all origins <0.0001). Compared to
      subjects with post-high school educations, those with high school educations were
      1.18 times more likely to be hospitalized (1.14-1.21), while those with
      elementary school educations experienced a risk of 1.32 (1.28-1.37) (P < 0.0001).
      Origin was a marked risk factor for hospitalization due to malignancy, with an
      odds ratio of 2.19 (1.71-2.79) for European-American origin relative to Israeli
      origin (P < 0.0001). The inverse association between education level and risk of
      hospitalization was constant across all diagnostic categories other than
      malignancy. CONCLUSIONS: Lower education was found to be a significant risk
      factor for hospitalization in most diagnostic categories. Origin was associated
      with increased risk for hospitalization due to malignant neoplasms and diseases
      of the respiratory, nervous, genitourinary and circulatory systems.

PMID- 15999560
TI  - [Indication for surgical intervention and surgical approach to complicated
      infective endocarditis].
AB  - Infective endocarditis is a disease with various presentations and conditions, so
      that the medical team faces many dilemmas, mainly on indications and timing for
      surgical intervention. The results of surgery depend upon many factors: the
      general preoperative condition of the patient, antibiotic treatment, timing of
      surgery, perioperative management, surgical techniques, postoperative management
      and follow-up. Optimal diagnosis and management of patients with infective
      endocarditis requires clinical judgment based on extensive experience. In spite
      of the current best practices and guidelines for surgical interventions in
      infective endocarditis, we face patients that do not "fall directly" into the
      obvious guidelines. This editorial covers some of the topics that remain
      controversial: timing for surgical interventions, selection of prosthetic valve
      type, technical aspects regarding complex infective endocarditis, and ethical
      decisions.

PMID- 15999561
TI  - [Intravenous immunoglobulin (IVIG) as treatment for recurrent pregnancy loss
      (RPL)].
AB  - Miscarriages are the most common complication in human pregnancies. Recurrent
      pregnancy loss (RPL) could occur for several reasons, such as: immunological
      abnormalities of the pregnant women and chromosomal abnormalities of the embryo.
      There are several autoimmune characteristics for RPL, such as autoantibodies, and
      sometimes RPL are a symptom of an autoimmune disease. It is unclear whether the
      autoantibodies are the cause, the consequence or an artifact of the RPL.
      Intravenous immunoglobulin (IVIG) is a preparation made of purified plasma of
      thousands of healthy donors. Currently, IVIG is provided as a treatment for
      several autoimmune diseases. There are reports on a beneficial effect of IVIG for
      women with RPL of unknown reason. Some reports indicate a beneficial effect of
      IVIG independent of aspirin, as well as in artificial fertilization.
      Nevertheless, the efficacy of IVIG has yet to be established. Perhaps a certain
      sub-group should be defined of women who suffer from RPL and have greater odds
      for successful IVIG treatment. A sub-group analysis showed that, in secondary
      RPL, IVIG is more successful when provided after embryo implantation, whereas, in
      primary RPL, IVIG is better when provided prior to conceiving. Apart from the
      miscarriage type (secondary or primary) other factors that might influence the
      IVIG-treatment success were found: the number of previous miscarriages, the age
      of the pregnant women and the way IVIG is administrated. The mechanisms of action
      of IVIG in RPL are multiple, complex and not fully understood. IVIG therapy
      regulates the immune system in several mechanisms, in a way that might increase
      the survival rate of the embryo in the uterus and might decrease the odds of a
      miscarriage. For example, one of the main mechanisms of IVIG in RPL is down
      regulation of natural killer cells (NK cells) activity and expression. This
      finding is of great importance because it has been reported that women who have
      never given birth and have high levels of NK cells in their peripheral blood have
      higher chances of pregnancy loss. In conclusion, IVIG is an immunomodulator that
      exerts its beneficial effects in multiple mechanistic ways acting together
      synergistically. IVIG is a potential treatment for women with RPL as a result of
      immunological abnormalities.

PMID- 15999562
TI  - [Surgical intervention in infective endocarditis: indications and timing].
AB  - A major advance has occurred over recent decades in the treatment strategies for
      infective endocarditis (IE). A significant part of this progress is due to a
      clearer knowledge of IE insult patterns; especially those concerning valvular
      damage and resultant heart failure. Furthermore, the existence of IE unique
      vegetations ensuring a suitable platform for organism growth and partial
      antibiotic resistance, has led to an understanding of the limited capacity of
      antibiotics to treat IE. Accordingly, an increased emphasis on surgical
      intervention has emerged. Indeed, the last decades were characterized by
      increased attempts to explore the feasibility and efficacy of surgical approach
      in IE. The present review is a result of these attempts, summarizing the major
      indications for surgical intervention in IE, as was recently published by the
      American Heart Association. Generally, such intervention is warranted in IE
      complications including: hemodynamically significant valvular damage,
      paravalvular abscess, continuous infection despite optimal treatment, recurrent
      emboli and antibiotic-resistant organisms. Recognition of the prognostic
      influence of pre-treatment heart failure degree has led to the development of
      early surgical intervention, namely, surgical intervention during the active
      period of IE. Application of such early intervention has led to survival rates
      which are significantly higher than achieved by antibiotic treatment per se.

PMID- 15999563
TI  - [Bronchiectasis--an orphan disease? Diagnosis and treatment in the 21st century].
AB  - Bronchiectasis has been termed an "orphan disease" since its decline in the
      developed world but it is still common in developing countries and in lower
      socioeconomic classes. Recurrent respiratory infections, under treatment with
      antibiotics and poor immunization rates are the main causes for the relatively
      high prevalence in these populations. Today the disease is not often adequately
      diagnosed nor treated. Airways dilatation, poor clearance of secretions and
      recurrent infections are the basis of the disease that is characterized by
      chronic productive purulent cough and recurrent exacerbations. The disease can be
      localized or diffuse, primary or secondary to other systemic disease. High
      resolution CT is the examination of choice for diagnosis. Lack of sufficient
      randomized control trials makes it difficult to establish guidelines.
      Nevertheless, partial information favors the use of prolonged antibiotic
      treatment, mucolytic agents and inhaled corticosteroids. Treatment should be
      tailored to the individual patient guided by the clinical picture while
      bronchodilators, bronchopulmonary hygiene and physical therapy are optional.
      Surgical resection is recommended for symptomatic localized bronchiectatic
      disease while lung transplantation should be reserved, as a last resort, for end
      stage bilateral disease.

PMID- 15999564
TI  - [Clinical and genetic aspects of congenital insensitivity to pain with
      anhidrosis].
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal
      recessive genetic disease, which is characterized by recurrent episodes of fever,
      anhidrosis, self mutilation, absence of reaction to noxious stimuli, prolonged
      healing times and mental retardation. The absence of pain sensation combined with
      mental retardation predisposes the children to recurrent wound infections and
      deep ulcers that heal at a slower pace than seen in healthy people. The anomalous
      pain is due to the absence of dorsal root ganglia that are responsible for pain
      sensation and absence of afferent neurons activated by tissue damaging stimuli.
      Nerve Growth Factor (NGF) is a growth factor that supports the survival of
      nociceptive sensory and autonomic sympathetic neurons. Neurotrophin Tyrosine
      Receptor (NTRK1) encodes a receptor tyrosine kinase that is activated in response
      to NGF. NTRK1 mutations have been found in mice that presented with clinical
      signs similar to CIPA, subsequently CIPA patients have been examined for these
      mutations as well. Currently, 37 different mutations at the NTRK1 are known which
      cause CIPA. The above syndrome is so rare that until the year 2000 only 84 cases
      have been reported, not including 28 known cases of CIPA patients from Israeli
      Bedouins. Since no cure is available, prenatal screening, as conducted in our
      institution, is the only available preventive option to avoid the birth of an
      affected child.

PMID- 15999565
TI  - [Psychiatry and psychotherapy in the managed care era: present and future in
      Israel and learning from the American experience].
AB  - The Israeli mental health system is undergoing reform, with privatization being a
      main component. This involves the transmission of responsibility from state to
      health maintenance organizations ("Kupot Holim"), similar to the situation in
      other medical domains, according to the Public Health Insurance Law. It is
      claimed that the anticipated reform is expected to reduce the quantity and
      quality of the mental health services that the public will receive. The insuring
      agencies will inevitably be motivated to save expenses throughout by means of
      limiting entitlement, access, investment and duration of mental health
      treatments. A survey of American literature reveals affluence of complaints and
      critics about the American private mental health insurance system, which may be
      briefly summarized in that "Managed care companies across the country have
      treated mental health coverage as if it were a treatment to be avoided at all
      costs". Henceforth, the prediction that the forthcoming Israeli reform is heading
      towards reducing the public mental health services which will be supplied to the
      citizens. This could thereby lead to discrimination between those who can afford
      private treatment and those who would receive minimal public treatment, if at
      all.

PMID- 15999566
TI  - [Low-weight and weight loss as predictors of morbidity and mortality in old age].
AB  - BACKGROUND: Elderly individuals who experience weight loss are at increased risk
      of premature death and disability. These data contradict findings among younger
      populations, showing direct relationship between Body Mass Index (BMI) and
      chronic diseases. METHODS: In the following manuscript we reviewed papers
      published in medical as well as in nutritional journals in the area of weight
      change, morbidity and mortality in old age, since 1990. RESULTS: Recent data
      indicates that among the elderly, unintentional weight loss of 5% of baseline
      weight during a period of 1 year marks the beginning of nutritional
      deterioration. As for BMI, in most studies that were reviewed for this
      manuscript, BMI of over 25 was protective. In a large study that was conducted in
      Hong Kong with 2032 participants aged 70 and older, low baseline weight was
      associated with mortality and was an independent predictor for the development of
      new diseases. In another large multicentered cohort study in the USA, 4714
      participants were followed. Mortality rates among weight losers were twice as
      high as mortality rates among the rest of the group. CONCLUSIONS: Low-weight and
      weight loss are independent predictors for mortality among the elderly
      population. There is a need to develop and implement screening methods for weight
      loss in all the medical settings that deal with elderly people. Additionally,
      there is a need for developing and assessing models for intervention among
      elderly people who are at nutritional risk.

PMID- 15999567
TI  - Corporate interests as an obstacle to the primary prevention of cancer.

PMID- 15999568
TI  - Multistate worklife expectancies.
AB  - This communication reviews the demographic concept of worklife expectancy and
      draws the epidemiologists' attention to its usefulness in occupational health
      research and pension policy making. The distinctions between different analytic
      approaches to the quantification of expected workforce status and mobility are
      pointed out. A recently developed multivariate large-sample regression method for
      the analysis of worklife tables is placed into the general context of life
      tables. Given aggregated data from multiple cross-sectional or longitudinal
      population surveys, a multistate regression model can be used to estimate
      consistently marginal probabilities that a person is in a given work-health state
      or transition probabilities between the states and, thereby, worklife
      expectancies. The methodology is illustrated through the application to data from
      Finnish population statistics on employment, disability, retirement, and
      mortality. The paper closes with a discussion of the methodological issues and
      empirical findings on pension policy in Finland.

PMID- 15999569
TI  - Shift work and the risk of diabetes mellitus among Japanese male factory workers.
AB  - OBJECTIVES: This study investigated whether shift work is a risk factor for the
      development of diabetes mellitus. METHODS: The workers, 2860 men in a sash and
      zipper factory in the Toyama prefecture of Japan, were followed for 8 years, and
      the incidence rate of diabetes mellitus was determined. The cohort contained
      fixed daytime blue-collar workers, shift blue-collar workers, and white-collar
      workers. The workers were considered to have diabetes mellitus if, in their
      annual health examination, they had a glycated hemoglobin level of > or = 6.1 or
      if the diagnosis had been made by a hospital physician. The relative risks were
      estimated by Cox's proportional hazards regression model. RESULTS: Among the 2860
      workers, there were 87 cases of new-onset diabetes mellitus, resulting in an
      incidence rate of 4.41 per 1000 person-years. The age-adjusted incidence was
      highest for the two-shift workers and lowest for the white-collar workers. The
      relative risk of diabetes mellitus for the two-shift workers and the three-shift
      workers compared with the fixed daytime workers was 1.73 and 1.33, respectively,
      after adjustment for all the confounding factors, but these values were not
      statistically significant. When the white-collar workers were used as a reference
      group, a significantly increased risk of diabetes mellitus was found for the two
      shift workers (relative risk was 2.01 after adjustment for all confounding
      factors), but not for the three-shift workers or the fixed daytime blue-collar
      workers. CONCLUSIONS: The study suggests that shift work is a risk factor for the
      onset of diabetes mellitus and that there is a different risk associated with
      different shift schedules.

PMID- 15999570
TI  - Model specification and unmeasured confounders in partially ecologic analyses
      based on group proportions of exposed.
AB  - OBJECTIVES: The aim of this study was to quantify bias from a partially ecologic
      analysis due to (i) model misspecification and (ii) an unmeasured confounder,
      considering various scenarios that may occur in occupational and environmental
      epidemiology. A study with an aggregate exposure variable, PE, but with outcome,
      group membership, and covariates assessed individually is partially ecologic. In
      this paper, PE is the proportion exposed; PE can vary across geographic areas or
      occupational groups. METHODS: Several hypothetical scenarios were considered,
      varying the baseline risk, the exposure effect, the exposure distribution across
      groups, the impact of the (unmeasured) confounder, and the confounder
      distribution across groups. First, confounding within groups was introduced.
      Thereafter, confounding between groups was introduced by co-varying PE and the
      confounder prevalence across the groups. The expected odds ratio (exposed versus
      unexposed) was calculated in two alternative models, the logistic regression and
      linear odds models, both with PE as the independent variable. Moreover, empirical
      data on noise exposure and sleeping disturbances were analyzed. RESULTS: Compared
      with the logistic regression model, the linear odds model yielded a markedly less
      biased odds ratio (OR) when the outcome was rare (< or = 5% baseline risk).
      Confounding within groups resulted in marginal bias, whereas confounding between
      groups resulted in more pronounced bias. CONCLUSIONS: A logistic regression
      analysis, with PE as an independent variable, can yield substantial model
      misspecification bias. By contrast, the linear odds model is valid when the
      outcome is rare. Confounding between groups should be of more concern than
      confounding within groups in partially ecologic analyses.

PMID- 15999571
TI  - Implementation of participatory ergonomics intervention in construction
      companies.
AB  - OBJECTIVES: The effectiveness of the implementation of participatory ergonomics
      intervention to reduce physical work demands in construction work was studied.
      METHODS: In a cluster randomized controlled trial, 10 bricklaying companies were
      randomly assigned either to an intervention group (N = 5) or a control group (N =
      5). The intervention strategy used a consultant-guided six-step approach in which
      company stakeholders participated. Bricklayers and bricklayers' assistants in the
      intervention group (N = 65) and the control group (N = 53) were followed for 6
      months, and their use of four ergonomic measures (adjusting work height when
      picking up bricks and mortar, adjusting work height for bricklaying at a wall
      side, mechanizing brick transport, and mechanizing mortar transport) was
      compared. The use of the ergonomic measures was assessed from worksite
      observations and questionnaires at baseline and after 6 months. The workers' and
      employers' behavioral change phases were determined by questionnaires and
      interviews, respectively. Performance indicators were assessed for the
      intervention from the researchers' observations during the implementation process
      and through questionnaires completed by the workers. RESULTS The strategy had no
      statistically significant effect on the use of any of the four ergonomic
      measures, at either the cluster or the individual level. None of the companies in
      the intervention group passed through all six steps of the intervention. Process
      outcomes suggest that the ability to use ergonomic measures increased. In
      bricklaying, self-efficacy and skills to adapt the work height on the scaffolding
      improved significantly. CONCLUSIONS: The intervention did not lead to greater use
      of ergonomic measures in bricklaying or the transport of materials. Performance
      indicators of intervention and the corresponding behavioral change phases of
      stakeholders can help to detect essential elements of such intervention.

PMID- 15999572
TI  - Registry-based case-control studies of liver cancer and cancers of the biliary
      tract nested in a cohort of autoworkers exposed to metalworking fluids.
AB  - OBJECTIVE: Results are presented for a registry-based study of hepatobiliary
      cancer (liver and biliary tract) nested in a cohort of workers from three
      automobile manufacturing plants with potential exposure to metalworking fluids.
      METHODS: Altogether 63 cases of hepatobiliary cancer were identified from the
      cohort by the Michigan cancer registries. Each case was matched to 10 controls.
      Odds ratios (OR) were estimated in conditional logistic regression models for
      lifetime exposure to straight, soluble, and synthetic metalworking fluid and
      fluid components. RESULTS: Overall, hepatobiliary cancer was not associated with
      exposure to metalworking fluids. However, when the cases were stratified into
      liver cancer (N = 39) and biliary tract cancer (N = 24) the risk was
      nonhomogeneous across the two categories. While liver cancer was not associated
      with exposure to metalworking fluids, the results suggested a possible excess
      risk of biliary tract cancer with more than 1.0 mg/m3-years of exposure to
      straight metalworking fluids [OR 2.7, 95% confidence interval (95% CI) 0.9-7.6],
      as well as any exposure to chlorinated paraffins (OR 3.9, 95% CI 0.9-17). When
      exposures to straight metalworking fluids were separated into 10-year exposure
      periods, the odds ratio increased to 6.24 (95% CI 1.62-24.16) for exposures
      occurring > 20 years prior to the risk date. CONCLUSIONS: There is limited
      evidence that exposure to straight metalworking fluids is associated with biliary
      tract cancer. The small numbers of cases of these rare cancers were reflected in
      the wide confidence intervals, and these findings need to be examined further in
      other exposed populations.

PMID- 15999573
TI  - Reproductive outcomes among hairdressers.
AB  - OBJECTIVES: The present study aimed at examining the possible risk of working as
      a hairdresser during pregnancy in relation to reproductive outcomes. METHODS: The
      Swedish Medical Birth Register, which includes almost every infant born in
      Sweden, has, since 1983, collected information prospectively about occupation in
      early pregnancy. This information is given at the first visit to a prenatal
      center. During the period 1983-2001, 12 046 infants were born to female
      hairdressers working either full- or part-time during early pregnancy. For
      comparison, all other deliveries during the same period were used in which the
      mother had worked either part-time or full-time. RESULTS: The full-time
      hairdressers more often had intrauterine growth-retarded infants (ie, small for
      gestational age) as compared with referents with a corresponding worktime
      [adjusted odds ratio (OR) 1.20, 95% confidence interval (95% CI) 1.06-1.36]. The
      pattern was similar for part-time hairdressers (adjusted OR 1.16, 95% 0.93-1.46).
      The fraction of malformations did not differ from those among the referents. The
      gender ratio for the infants of hairdressers was similar to that for the overall
      Swedish population. CONCLUSIONS: The findings concerning infants small for their
      gestational age in the present study is in accordance with previous findings. The
      reason for these findings remains unknown. Studies with more-specific exposure
      information during pregnancy are needed.

PMID- 15999574
TI  - Psychosocial factors at work and myocardial infarction among men in Kaunas,
      Lithuania.
AB  - OBJECTIVES: The association between job demand and job control and first nonfatal
      myocardial infarction was studied among the 25- to 64-year-old male population in
      Kaunas, Lithuania. METHODS: A translation of the Swedish version of the demand
      control questionnaire was used. Both psychosocial work characteristics as
      independent risk factors and the possible effects of traditional risk factors
      (smoking, arterial hypertension, overweight) were analyzed in a case-control
      study among 203 men diagnosed in 2001-2002 with a first nonfatal myocardial
      infarction (cases) and 287 men randomly selected as controls. A logistic
      regression analysis was used to estimate the odds ratio for developing myocardial
      infarction in relation to self-reported job demand and job control. Possible
      confounders (age, marital status, education, type of occupation, smoking, blood
      pressure, body mass index) were controlled. RESULTS: The adjusted odds ratio was
      0.56 [95% confidence interval (95% CI 0.37-0.85)] and 1.53 (95% CI 1.04-2.38),
      for demand and control, respectively. That for workers with low demand and low
      control was 1.89 (95% CI 0.99-3.60) as compared with low demand and high control.
      The risk of myocardial infarction for men in passive jobs (low demand and low
      control) was twofold that of the other respondents. CONCLUSIONS: The association
      between low job control and the risk of myocardial infarction was found to be
      consistent with research in western populations. In contradiction, however, to
      findings in western studies, low demand, rather than high demand proved to be a
      risk factor for 25- to 64-year-old men. Employees in passive jobs had the highest
      risk.

PMID- 15999575
TI  - Irritant vocal cord dysfunction at first misdiagnosed as reactive airway
      dysfunction syndrome.
AB  - OBJECTIVES: This report describes a case of vocal cord dysfunction at first
      misdiagnosed as reactive airway dysfunction syndrome (RADS). METHODS: A woman
      developed recurrent episodes of cough, dyspnea, and wheezing unresponsive to
      asthma therapy after irritant exposure to glutaraldehyde. Direct laryngoscopy was
      performed immediately after the induction of symptoms. RESULTS: Laryngoscopy
      showed a paradoxical adduction of the vocal cord on inspiration. Vocal cord
      dysfunction was diagnosed. CONCLUSIONS: A case of vocal cord dysfunction occurred
      after exposure to glutaraldhyde in a person with a history highly suggestive of
      RADS. Vocal cord dysfunction should always be considered in the differential
      diagnosis of patients with acute respiratory symptoms after exposure to irritants
      and with asthma-like symptoms that fail to respond to conventional asthma
      therapy.

PMID- 15999576
TI  - Primary prevention of cancer in relation to science, sociocultural trends and
      economic pressures.

PMID- 15999578
TI  - Assessing the work-relatedness of nonspecific low-back pain.

PMID- 15999577
TI  - Epidemiologic evidence for the carcinogenicity of vinyl chloride monomer.

PMID- 15999579
TI  - [Strategies and results of structured treatment programs in diabetic care in
      Germany--a look back].

PMID- 15999580
TI  - [Demands on the evaluation of complex healthcare programs--disease management in
      Germany].
AB  - Disease management programs (DMP) are a new method of healthcare in Germany.
      Their implementation is legally secured and binding. Besides the requirements of
      a comprehensive documentation and the obligation to provide guideline-oriented
      healthcare, the statutory health insurances are also obliged to carry out a DMP
      evaluation. For this evaluation, a scientific advisory council of the Federal
      Insurance Office has submitted specific relevant criteria. The present
      contribution considers these criteria and relates them to the evaluation
      standards of the Evaluation Research Society. Additionally, some specific
      conditions for the undertaking of DMP and their evaluation in Germany are taken
      into consideration. The article ends with a suggestion for a comprehensive and
      methodologically accurate discussion.

PMID- 15999581
TI  - [Evaluation of the pilot project for the gradual area-wide outpatient medical
      care of patients with diabetes mellitus in Southern Wuerttemberg].
AB  - The aim of the diabetes pilot project of the AOK Baden-Wuerttemberg and the KV
      Southern Wuerttemberg was to prevent diabetes-related complications or to delay
      their progress by attaining predefined, short-term therapy goals (e.g.,
      stabilization of HbA1c and blood pressure levels). Besides the observation of the
      short-term therapy aims, the scientific monitoring also included the development
      of the healthcare structure and the changes of the healthcare processes. Measured
      against the HbA1c value of the 13.902 patients suffering from type-2 diabetes
      included in the first 6 months of the year 2000, an improvement of the outcome
      quality (HbA1c < or = 7.5%) could be observed with an increased goal attaihment
      degree of 66.6% (IV/2002) compared to the initial value of 60.3% (p < 0.001). The
      predefined blood pressure levels (< or = 140/90 mmHg) were achieved by 55.8% of
      the patients at the beginning and by 64.6% at the end of the evaluation period (p
      < 0.001). In terms of healthcare processes, an intensification of the medicinal
      therapy is remarkable.

PMID- 15999582
TI  - [Improved diabetes care in Saxony Anhalt--results of the evaluation of the
      diabetes model project (first quarter 2001-last quarter 2002)].
AB  - Approximately 5-6% of the German adult population suffers from diabetes, and the
      disease prevalence is expected to increase in the future. On the other hand,
      epidemiological studies show that early diagnosis, qualified training, and
      individualised therapy increase the quality of life of the patients and decrease
      the costs of treatment. A diabetes disease management trial was conducted in
      Saxony Anhalt in the years 2001 and 2002. The programme objective was to improve
      quality and efficiency of diabetes care. The study assessed the effects of a
      managed care approach, which included treatment corridors, patient education, and
      documentation of medical findings. A total of 19,957 patients and 263 physicians
      participated in the trial. The results of the evaluation show a professional and
      continuous supervision by physicians taking part in the programme. In comparison
      to the control group, patients enrolled in the plan displayed to a larger extent
      stabilised or lower (in some cases normalised) diabetes parameters, i.e., HbA1c
      levels, blood pressure, occurrence of hypoglycemia. During the trial phase, the
      total spending for plan participants was 0.85% lower than for non-programme
      patients. Lower primary care costs were overcompensated by reduced in-patient
      spending. The cost saving can be attributed, among others, to fewer
      hospitalisations and inpatient services for the treatment of diabetes.

PMID- 15999583
TI  - [Exploratory evaluation of a model project for the structured delivery system in
      Saxony-Anhalt in the year 2001].
AB  - A model project for a structured health delivery system for type-2 diabetes was
      scrutinized regarding levels of awareness, motivation, expectations, and
      acceptance among the participating target groups by using psychological
      exploratory in-depth-interviews. Patients experience a positive increase of
      regularity in their treatment, but overall the project remains unclear to them.
      General practitioners experience a positive image change, increased clarity, and
      reduced workload. These advantages help them to tolerate the inherent burden of
      documentation. Expectations regarding treatment quality are generally met,
      however expectations regarding the formal organization of the project remain
      often unmet. Physicians with special expertise often develop very high
      expectations, but these are not always fulfilled. One successful aspect of the
      project is the adequate handling of existing psychological treatment problems
      (and corresponding needs), which results in good acceptance and motivation to
      participation.

PMID- 15999584
TI  - [Exploratory study on the positive participation in the DMP Type-2 Diabetes
      Mellitus in Westphalia Lippe].
AB  - This exploratory study, carried out on behalf of an association of German health
      insurers, the AOK Bundesverband, examined the positive, subjective effects on
      patients participating in the Westphalia Lippe DMP Type-2 Diabetes Mellitus
      ('Curaplan', started June 2003) in terms of coping with diabetes and handling the
      disease. A two-stage qualitative method was selected: First, 250 respondents were
      questioned using 15-20 minutes half-structured telephone interviews;
      approximately 40% of the interviewed reported a subjective improvement related to
      participation in the Curaplan program. In a second step, in-depth interviews were
      then carried out with 50 of the respondents who had reported a profit from the
      program. Analyses proceeded in a phenomenon-oriented fashion according to a
      differentiation and a general psychological-coping perspective. At a
      differentiation level, eight modes of coping with the illness were reconstructed,
      for each of which respondents identified a specific improvement. These were:
      "Consistent/rational commitment", "Discovery-oriented acceptance of challenge",
      "Search for illness-mediated compromise", "Anxious quest for increased control",
      "Blinkered denial", "Hopelessness", "Inability to cope and insecurity", "Selfless
      low prioritization of disease". At a general level, five central positive
      dimensions of participation were observed: "Relationship/not being alone",
      "Meaning/importance", "Knowledge/consciousness", "Ability to manage/competence
      gain", as well as "Happiness/optimism". These dimensions complemented and
      supported one another. The results are not statistically representative but
      contribute to optimized implementation through psychological understanding of the
      best cases. Further studies should examine correlations of subjective processes
      with objective variables.

PMID- 15999585
TI  - [Patient-oriented healthcare programs. Concepts and practical experience in the
      field of chronic heart failure].
AB  - Disease management programs (DMP) have been recently introduced in the German
      statutory healthcare sector by federal law. These compulsory programs are aimed
      at enhancing guideline-based treatment by primary care physicians. Based on a
      systematic analysis of disease models and deficits in healthcare delivery,
      patient-oriented DMP offer an alternative approach. Their standardized services
      include care calls, written educational material, reminder systems, health
      reports, and optional telemetric monitoring. As an example of this approach, the
      medical results of 151 patients participating in a comprehensive chronic heart
      failure (CHF) program were evaluated. Within the observation period of 12 months,
      the number of patients receiving appropriate prescriptions (ACE inhibitors,
      diuretics, or beta blockers) rose significantly. In many patients there was a
      remission of CHF key symptoms (leg edema, shortness of breath, dizziness). The
      daily weight monitoring was particularly appreciated by the patients. For further
      development of patient-oriented DMP in the German healthcare system, it will be
      crucial that financial savings can be convincingly demonstrated besides the
      clinical benefits. These include quality of life, particularly for those chronic
      conditions in which patient self-management has a large impact on disease course.

PMID- 15999586
TI  - [Suspicion of COPD--development of an algorithm for stepwise diagnosis in primary
      care].
AB  - The implementation of the disease management programme (DMP) for asthma and COPD
      in the German health system in 2005 requires an optimal and evidence-based work
      up of patients by general practitioners in routine daily practice. The German and
      international guidelines for COPD do not provide recommendations for a stepwise
      diagnostic work-up in primary care. Therefore, an evidence-based algorithm was
      developed for a stepwise diagnosis of COPD and its different stages in general
      practice, based on national and foreign guidelines that provide specific advice
      on diagnostic procedures.

PMID- 15999587
TI  - [Rigid RSA DMP for Type-2 Diabetes Mellitus: results of a three-state survey].
AB  - Diabetes contracts, such as those used in Saxony, were already excellent,
      effective diabetes programs in line with the concept of disease management. This
      was due to well-accepted practical guidelines and to an integrated care concept
      that was implemented with little bureaucratic effort through an internal quality
      control management; this was based in turn on rapid, practicable documentation in
      the framework of interdisciplinary quality round tables. The present RSA DMP, in
      contrast, are to be fundamentally improved and simplified. This must occur also
      in view of the handling of guidelines, so that these do not jeopardize well
      established and positively-evaluated healthcare programs (and along with that the
      quality of patient care) in the regions with well-functioning systems. In view of
      the persistent critiques on form and content of the state-regulated chronic
      disease programs, the group "DMP in Central Germany", representing the German
      federal states of Saxony, SaxonyAnhalt, and Thuringia, initiated at the end of
      2003 a structured survey for the evaluation of the RSA DMP Type 2 Diabetes among
      general practitioners and diabetes specialists. Particularly critical evaluations
      of the RSA DMP originate from the federal states with well-developed guideline
      based diabetes care programs, for example in the new Eastern federal states, Nord
      Rhine-Westphalia, and Bavaria. With its minimal standards, the RSA DMP does not
      represent any progress in these regions and does not contribute to cost
      reduction. Detailed medical contents and professional guidelines do not belong to
      a law ordinance but to the already existing medical guidelines.

PMID- 15999588
TI  - [Important early symptoms in central nervous system diseases].

PMID- 15999589
TI  - [Criticism and counter-criticism of health care delivery in Germany].

PMID- 15999590
TI  - [Short report on the German Health Technology Assessment].

PMID- 15999591
TI  - [Disease management program in Nordrheim--first results on data management and
      care of participants].

PMID- 15999592
TI  - [10 years of a community quality program in Germany. The projected program and
      networks on the challenge of quality and evidence in medicine].

PMID- 15999593
TI  - [Erectile dysfunction: a sentinel symptom?].
AB  - Erectile dysfunction (ED) is a frequent disorder affecting the man's sexual and
      relational quality of life. French epidemiological studies estimate that the
      prevalence of ED is between 11% and 44% and prevalence surveys show a correlation
      between ED and age: the relative risk of erectile dysfunction increases by a
      factor of 2 to 4 between the ages of 40 and 70 years. Few patients consult their
      doctor and only a small proportion of them receive treatment and few doctors take
      the initiative to discuss the question of their patients' sex life. Doctors
      should now have a good understanding of erectile dysfunction and must be aware of
      the importance of detecting or at least investigating any erectile dysfunction,
      which can be the first symptom of an underlying disease such as cardiovascular
      disease, diabetes, depression, benign prostatic hyperplasia, prostate cancer,
      androgen deficiency or a drug-induced effect. Demonstration of erectile disorders
      therefore represents an excellent opportunity to conduct a general work-up, as
      more than one-third of patients with ED ignore their underlying health problem
      and management of ED is therefore an integral part of preventive medicine.

PMID- 15999594
TI  - [Adjuvant chemotherapy and/or hormone therapy after radical prostatectomy for
      high-risk prostate cancer].
AB  - Cancer prostate is heterogeneous and may require a risk-adjusted approach to
      therapy. Improved survival rates are reported for adjuvant chemotherapy alone or
      in combination with hormone therapy. A specific gene expression signature can be
      used to identify and predict response to adjuvant standard hormone therapy or
      hormone therapy and chemotherapy after radical prostatectomy.

PMID- 15999595
TI  - [Candiduria].
AB  - Fungal urinary tract infections, especially those caused by Candida species, have
      become increasingly frequent over the last decade, especially in hospitalized
      patients. However, no clearly defined criteria can distinguish between
      colonization and infection or between upper and lower urinary tract infection.
      The authors review the risk factors, epidemiology and pathogenesis of candiduria
      and propose diagnostic and treatment strategies for most of the situations
      encountered in clinical practice.

PMID- 15999596
TI  - [Should the contralateral testis be systematically biopsied after orchidectomy
      for unilateral germ cell tumour of the testis?].
AB  - Intratubular neoplasia (ITN) of the testis is a precursor of germ cell tumour,
      apart from spermatocytic seminoma. It is often detected in testicular tissue
      adjacent to germ cell tumours, but is less common in the contralateral testis.
      Early diagnosis of ITN by testicular biopsy would allow earlier, conservative
      management. However, this approach remains highly controversial except in very
      specific indications.

PMID- 15999597
TI  - [Pyeloplasty: aesthetic benefit of lumboscopy].
AB  - STUDY OBJECTIVE: To evaluate the aesthetic benefit of lumboscopy versus lumbotomy
      in a group of patients undergoing pyeloplasty. MATERIAL AND METHOD: A telephone
      survey was conducted in 103 people operated by pyeloplasty via lumboscopy or
      lumbotomy. The questions concerned the appearance of the scar (size, relief;
      visible or invisible), skin complications, satisfaction with the scar,
      postoperative pain, length of hospital stay and return to physical activity or
      work. RESULTS: The response rate was 58.2% corresponding to 32 lumboscopies and
      29 lumbotomies. Lumboscopy scars were shorter (2.7 vs 15.6 cm for lumbotomies,
      p<0.001). Lumbotomy scars were palpable in 75% of cases versus 53.1% of
      lumboscopy scars of (p=0.037). Almost 96.5% of lumbotomy scars were visible
      versus only 68.7% of lumboscopy scars (p=0.0057). Lumbotomies were complicated by
      incisional hernia in 14.2% of cases, while no incisional hernias were observed in
      the lumboscopy group (p=0.02). 85% of patients were satisfied with their scars in
      the lumboscopy group versus 56% of patients operated by lumbotomy (p=0.0286).
      CONCLUSION: This study showed a statistically significant difference in terms of
      a purely aesthetic benefit and scar solidity in favour of lumboscopy, which
      supports the growing place of this surgical technique in urology.

PMID- 15999598
TI  - [Laparoscopy in the management of upper urinary tract stones based on a series of
      18 cases].
AB  - OBJECTIVE: To evaluate the efficacy and morbidity of laparoscopic surgery in the
      management of upper urinary tract stones. MATERIAL AND METHOD: Between January
      1998 and July 2004, 18 patients (14 males, 4 females) underwent laparoscopic
      extraction of an upper urinary tract stone. Stones were lumbar (n=13),
      ureteropelvic (n=2), iliac (n=1), inferior caliceal (n=1), and intradiverticular
      (n=1) with a mean diameter of 15 mm (range: 8-25 mm). Fifteen stones were
      obstructive. Laparoscopy was performed after failure of one or several previous
      treatments in 9 cases: ESWL (n=2), retrograde (n=1), anterograde ureteroscopy
      (n=6). A retroperitoneal approach (n=15) was used for caliceal and lumbar stones
      and a transperitoneal approach (n=3) was used for pyeloureteric and iliac stones.
      RESULTS: The mean operating time was 80 minutes (range: 40-150 min). The mean
      blood loss was 50 cc (range: 0-250 cc). The mean length of stay was 3.86 days
      (range: 2 to 7 days). Fifteen patients were drained by a double J stent for one
      month. The stone was removed by laparoscopy in every case. One patient developed
      a urinoma requiring surgical repair via a lumbar incision. CONCLUSION:
      Laparoscopy currently constitutes an attractive alternative for the treatment of
      upper urinary tract stones and, in this study, was indicated for first-line
      treatment of obstructive stones larger than 12 mm impacted in the ureter or after
      failure of previous treatments.

PMID- 15999599
TI  - [Ureterocele in adults based on a series of 14 cases].
AB  - OBJECTIVE: To evaluate the efficacy of endoscopic meatotomy in the treatment of
      ureterocele in adults and to determine the incidence of its main complication,
      vesico-ureteric reflux. MATERIAL AND METHOD: Retrospective study of 14 cases of
      ureterocele in adults observed between March 1989 and August 2004, corresponding
      to 7 males and 7 females with a mean age of 39 years (range: 17-73 years). The
      ureterocele was observed in a context of single ureter in 13 cases (94%) and
      duplicated ureter arising from the superior renal unit in one patient (7%). The
      ureterocele was complicated by stones in 9 cases (64%). Endoscopic meatotomy was
      performed in 13 patients, while immediate resection of the ureterocele followed
      by Hendren ureterovesical reimplantation was performed in one patient with major
      proximal repercussions. RESULTS: The postoperative course was uneventful in all
      patients including the patient treated by conventional surgery. Postoperative
      follow-up consisted of clinical and radiological assessment at 3 months and 6
      months. Endoscopic treatment was effective in every case with resolution of low
      back pain and absence of residual stones when the ureterocele was initially
      complicated by stones. In contrast, de novo vesicoureteric reflux appeared
      secondarily in 5 patients (38.5%) but persisted at 6 months in only one patient,
      who required re-operation: resection of the ureterocele and Hendren ureteric
      reimplantation. CONCLUSION: Endoscopic meatotomy can be considered to be the
      firstline treatment for ureterocele in adults in the absence of severe dilatation
      of the proximal urinary tract. Its main complication remains vesico-ureteric
      reflux. Radiological surveillance by urethrocystography therefore appears to be
      essential.

PMID- 15999600
TI  - [Cystomanometric study of bladder sensation during sacral neuromodulation test].
AB  - PURPOSE: Prospective clinical and urodynamic study evaluating modification of
      bladder sensation during sacral neuromodulation (SNM). MATERIALS AND METHODS: 24
      consecutive patients with non-neurological hyperactive bladder underwent an SNM
      test. Questioned about their symptoms before and during the test by the urinary
      handicap assessment scale, patients were divided into two groups: A (improved)
      and B (not improved). Group A consisted of patients obtaining 50% improvement of
      their symptoms with SNM followed by return of symptoms at the end of the test,
      while the other patients constituted group B. We then compared the
      cystomanometric results according to their clinical response. RESULTS: The mean
      age was 53 years: 10 patients with a good response constituted group A (n=10,
      i.e. 42%) and 14 patients with a poor response constituted group B (n=14, i.e.
      58%). Clinically, in patients with a good response, SNM decreased urge
      incontinence by 100%, day-time frequency by 89% and protections by 55%.
      Urodynamic assessment in group A during the test demonstrated a significant
      increase of +23% of bladder capacity (p<0.01), +57% of the volume of onset of the
      first unstable contraction (p<0.004), +83% of bladder volume to the first urge to
      urinate BI (p<0.001) and +46% to urgency B3 (p<0.04). During SNM, cystometry
      revealed that 1 or 2 bladder filling volumes were increased at B1 and/or B3 in
      100% of improved subjects. In contrast, 1 or 2 volumes decreased at B1 and/or B3
      in 58% of non-improved subjects. No significant difference of intensity of
      unstable contractions was observed between the 2 groups during SNM (p=0.31).
      CONCLUSION: A significant correlation was observed between the two methods of
      clinical and urodynamic assessment. Our results suggest the use of the
      cystomanometric increase of bladder volume at B1 and B3 as selection criterion
      for candidates for SNM with non-neurological hyperactive bladder.

PMID- 15999601
TI  - [Results of the AMS 800 artificial urinary sphincter in men, based on a series of
      47 patients].
AB  - INTRODUCTION: Male urinary incontinence due to sphincter incompetence is usually
      secondary to prostate surgery. After failure of other treatments, severe
      sphincter incompetence requires placement of an artificial urinary sphincter The
      authors present the results of the AMS 800 artificial urinary sphincter based on
      a series of 47 consecutively operated patients. PATIENTS AND METHODS: From 1990
      to 2003, 47 AMS 800 were inserted by the same operator and according to the same
      technique. The aetiologies of urinary incontinence were: radical prostatectomy
      (45% of cases), transurethral resection of the prostate (36%), open prostatectomy
      (10.5%), and others (8.5%). RESULTS: The mean age of the patients was 65 years.
      The mean follow-up was 36 months. The mean time to insertion was 3 years and 10
      months (range: 5 months-15 years). 23.4% of patients presented one or several
      complications (mechanical failure: 19%; infection; 10.6%; erosion: 4%; bladder
      stones: 2%), 21% of patients required one or several surgical revisions after a
      mean interval of 25.5 months (range: 2-80 months). The actuarial 5-year revision
      rate was 25.5%. With a mean follow-up of 36 months, 98% of patients had a
      functioning artificial urinary sphincter and 83% still had their original
      artificial urinary sphincter Social continence and patient satisfaction rates
      were 87% and 95.7%, respectively. CONCLUSION: These results are comparable to
      those of similar published series. The AMS 800 is associated with high continence
      and patient satisfaction rates and currently remains the reference treatment for
      refractory sphincter incompetence in men.

PMID- 15999603
TI  - [An experience of individual and early diagnosis of prostate cancer in a Tunisian
      centre].
AB  - INTRODUCTION: The introduction of prostate specific antigen (PSA) and progress in
      transrectal ultrasound and ultrasound-guided prostatic biopsies have allowed
      considerable progress in the diagnosis of prostate cancer. However prostate
      cancer is still usually diagnosed at an advanced stage in Tunisia. METHODS: We
      prospectively evaluated the prevalence of localized prostate cancer in the
      population of a Tunisian centre during a screening programme. This study included
      all men consulting for a urological problem between January 1998 and June 2001,
      between the ages of 50 and 75 years with an estimated life expectancy of at least
      10 years. Screening consisted of digital rectal examination (DRE) and total and
      free PSA assay. Systematic ultrasound-guided prostatic biopsies (9 biopsies) were
      performed in the case of a suspicious DRE, total PSA between 4 and 20 ng/ml and a
      free PSA/total PSA ratio less than 25%. RESULTS: 642 patients were screened. 521
      patients (81%) had a PSA less than 4 ng/ml, 23 had a suspicious DRE and PSA less
      than 4 ng/ml. No cancer was detected by prostatic biopsies. 92 patients (14%) had
      a PSA between 4 and 20 ng/ml and 44 of them had a free PSA/total PSA ratio less
      than 25%. Prostatic biopsies were performed in 59 of these 92 patients with PSA
      between 4 and 20 ng/ml and revealed 18 cancers: 3 stage pN+ and 15 stage pN0,
      including 1 stage pT3 and 14 stage pT2 after radical prostatectomy. 14 cancers
      detected in a population of 642 men (2.2%) were therefore stage pT2. 29 patients
      (4.5%) had a PSA higher than 20 ng/ml. All underwent surgical prostatic
      disobstruction demonstrating adenocarcinoma. A total of 47 cancers (7.3%) were
      therefore detected. CONCLUSION: Early individualized screening is possible in
      Tunisia and allows the detection of localized prostate cancer in 77% of patients
      with PSA less than 20 ng/ml. The use of prostatic biopsies in the case of
      abnormal screening tests improves the management of prostate cancer in Tunisia.

PMID- 15999602
TI  - [Prognostic value of stromal immunolabelling by MMP-2, MT1-MMP and TIMP-2 in
      clinically localized prostate cancer].
AB  - INTRODUCTION: Metalloproteinases (MMPs) promote cell migration and tumour
      invasion by degradation of the extracellular matrix. Activators and inhibitors
      (such as membrane type 1-matrix metalloproteinase or MT1-MMP and tissue inhibitor
      metalloproteinase 2 or TIMP-2) regulate metalloproteinase activity. The objective
      of this study was to determine the prognostic value of stromal immunolabelling
      with MMP-2, MT1-MMP and TIMP-2 in clinically localized prostate cancer. MATERIAL
      AND METHODS: The immunohistochemical study was performed on 30 radical
      prostatectomy specimens. The results were compared to preoperative PSA, Gleason
      score, pT stage and biochemical recurrence with a minimum follow-up of 5 years.
      RESULTS: Stromal immunolabelling with MMP-2 is correlated with stage pT3
      (p=0.0022, OR=17.5). No correlation was observed with the other histoprognostic
      parameters. No statistical link was established with MT1-MMP and TIMP-2.
      CONCLUSION: Stromal immunolabelling with MMP-2 is a histoprognostic marker of
      capsular effraction in prostatic adenocarcinoma. When performed on prostatic
      biopsies, it can predict the pT3 stage, allowing adaptation of the initial
      treatment in some patients.

PMID- 15999604
TI  - [Prostate cancer at high risk of recurrence: results of 12 months of radiotherapy
      hormone therapy].
AB  - OBJECTIVE: To evaluate the risk of progression after conformal radiotherapy
      combined with 12 months of adjuvant hormone therapy in a series of patients with
      prostate cancer considered to be at high risk of progression. MATERIAL AND
      METHODS: Between January 1997 and December 2001, 63 consecutive patients
      classified at high-risk according to Amico's classification were treated by
      combined radiotherapy-hormone therapy. All patients presented at least one factor
      of the high-risk group of Amico's classification: TNM 92 stage T2c, T3 or T4, or
      Gleason score > or = 8 or baseline PSA > 20 ng/ml. All patients were treated by
      combined radiotherapy-hormone therapy with concomitant hormone therapy for 2
      months and adjuvant hormone therapy for 10 months. Biochemical progression was
      defined according to the ASTRO criteria. The median follow-up was 36 months.
      RESULTS: The 3-year and 5-year biochemical recurrence-free survival was 78%. No
      local recurrence was observed in 94% of cases and no metastases were observed in
      93% of patients. On univariate analysis, only a baseline PSA greater than 22
      ng/ml was identified as a predictive factor of early biochemical recurrence. The
      3-year biochemical recurrence-free survival was 96% for patients with baseline
      PSA < 22 ng/ml and 56% for patients with baseline PSA > or = 22 ng/ml (p=0.0017).
      CONCLUSION: The early results of 12 months of radiotherapy-hormone therapy in
      high-risk patients in our series were comparable to those reported in the
      literature. Only a high baseline PSA was predictive of early biochemical
      recurrence. Adjuvant hormone therapy (long-term, intermittent hormone therapy)
      could therefore be modulated as a function of the baseline PSA.

PMID- 15999605
TI  - [Descending perineum in women].
AB  - The descending perineum syndrome, described in 1970 by Alan Parks, remains
      difficult to interpret clinically and pathophysiologically. A general review of
      descending perineum was conducted, based on review of the literature published
      between 1966 and 2004, and retrospective analysis of 1,023 colpocystograms. The
      symptoms observed are usually secondary to associated lesions. Radiological signs
      of descending perineum are not always associated with clinical symptoms.
      Colpocystogram shows perineal descent and associated disorders of anterior and
      middle pelvic tone, while defecography provides a better explanation for
      dyschezia which is generally due to an associated posterior disorder (rectocele
      with rectal intussusception). The management of descending perineum is based on
      medical treatment and retraining. No consensus has been reached concerning
      surgical management. Surgery is generally used to treat associated lesions. In
      the case of complete collapse of perineum, an abdominal approach with
      infravesical, prerectal and retrorectal tension-free tape to the sacrum could be
      useful, while transanal staple repair of the rectum could be proposed when
      descending perineum is associated with only rectal intussusception or rectocele.

PMID- 15999606
TI  - [Is colpocleisis still indicated for the treatment of female genitourinary
      prolapse?].
AB  - OBJECTIVE: To analyse the place of colpocleisis in the treatment of genitourinary
      prolapse with or without stress urinary incontinence. MATERIAL AND METHODS: The
      authors retrospectively reviewed 19 patients operated for advanced genitourinary
      prolapse associated with stress urinary incontinence in 11 cases. The surgical
      technique was the Le Fort procedure, either alone or combined with TVT placement.
      Le Fort procedure was indicated by the patient's age, contraindications to other
      surgical procedures and absence of sexual activity. Objective criteria of cure
      and subjective criteria were studied with assessment of the repercussions of
      treatment on quality of life by appropriate questionnaires. RESULTS: The Le Fort
      procedure gave excellent long-term results with low morbidity. It could be
      combined with TVT placement without altering the results. No recurrence of
      genitourinary prolapse was observed during follow-up. The patient satisfaction
      index was close to 90%. CONCLUSION: The Le Fort procedure should be performed in
      selected cases when conventional surgery can no longer achieve a satisfactory
      result. It can also be combined with treatment of stress urinary incontinence.

PMID- 15999607
TI  - [Section of intravesical TVT tape by a suprapubic trocar].
AB  - Since its first description in 1995, treatment of female urinary incontinence by
      TVT has become a routine procedure. The ascending retropubic approach can lead to
      a number of complications. Bladder trauma is observed in 2% to 20% of cases
      depending on the series. They do not have any repercussions if they are diagnosed
      and repaired intraoperatively, but, when they are detected later, they raise
      problems of diagnosis and management. The authors report 2 cases in which a
      combination of cystoscopy and laparoscopy was used to section intravesical TVT.

PMID- 15999608
TI  - [Treatment of urinary stones in infants].
AB  - Up until the beginning of the 1990s, surgery was the only available modality for
      the treatment of renal and ureteric stones in infants. From 1990 onwards, two new
      minimally invasive techniques were developed, leading to a real revolution in the
      management of these patients. The first and most spectacular breakthrough was
      extension of the application of ESWL to this age-group and the second
      breakthrough was ureteroscopy following the enormous technological progress in
      the manufacture of endoscopes. This technique is increasingly useful when
      lithotripsy is impossible or insufficient. Surgery is still indicated in the case
      of contraindications to minimally invasive methods or after failure of these
      methods. It is the method of choice for bladder stones. Medical treatment or
      watchful waiting have valuable indications, at the cost of regular clinical and
      radiological follow-up of patients. The choice of treatment modality depends on
      the size of the stone, its site, its composition, the anatomy of the urinary
      tract and the availability of the various techniques.

PMID- 15999609
TI  - [Renal transplantation techniques in children with impaired patency of the
      inferior vena cava or iliac vein].
AB  - INTRODUCTION: Congenital or acquired disorders of patency of the inferior vena
      cava (IVC) or iliac veins have been considered for a long time to be an almost
      insurmountable technical obstacle in paediatric renal transplantation. The
      authors report their experience based on 7 transplantations performed in children
      with a disorder of venous patency, in whom renal transplantation was able to be
      performed. More generally, they also discuss the available technical options
      based on a review of the literature. MATERIAL AND METHOD: From April 1987 to
      January 2002, renal transplantation was performed in 7 children with congenital
      or acquired abnormality of the iliac veins or IVC in our unit. All children
      underwent radiological assessment by venous Doppler ultrasound before
      transplantation. The contribution of radiological examinations to the diagnosis,
      the surgical technique performed, postoperative complications, patient survival
      and graft survival as well as long-term renal function were studied
      retrospectively. RESULTS: Four of the 7 transplanted children presented a
      congenital anomaly of the IVC and 3 had acquired thrombosis. In 5 out of 7 cases,
      the diagnosis was established before transplantation by Doppler ultrasound
      (completed by cavography in one case). The transplant renal vein was anastomosed
      to the iliocaval system in the majority of cases and the portal system had to be
      used in one case. With a mean follow-up of 94 months, all children have a
      functioning graft with a mean serum creatinine of 88 micromol/l. CONCLUSIONS:
      Disorders of patency of the IVC or iliac veins in children waiting for renal
      transplantation are rare, but these abnormalities can cause problems for the
      surgical team and compromise graft survival. Radiological assessment of patency
      of the venous network must help to demonstrated these abnormalities in order to
      optimally adapt the transplantation technique, which ensures very acceptable
      graft survival rates.

PMID- 15999610
TI  - [Failures of endoscopic treatment of vesico-ureteric reflux in children using
      Macroplastique].
AB  - INTRODUCTION: Macroplastique has been used since 1993 for the endoscopic
      treatment of vesico-ureteric reflux in children with a failure rate per injected
      ureteric unit of 21%. The objective of this study was to analyse these failures
      on the basis of endoscopic findings on injection, ultrasound data at 2 months
      post-endoscopy and operative findings during the secondary reimplantation.
      MATERIAL AND METHODS: The authors retrospectively reviewed cases of failure of
      Macroplastique treatment from September 1993 to December 2002. Only children
      undergoing subsequent surgical reimplantation were included in the study: 60
      cases (57 girls, 3 boys). Another 68 patients also presented recurrence of
      reflux, but are currently asymptomatic and have not been reoperated. Twenty five
      patients (42%) initially presented unilateral vesico-ureteric reflux: bilateral
      injection was performed in 17 of these cases because of the anatomical findings
      on endoscopy. In 92% of cases, the refluxing ureteric orifice appeared to be
      abnormal (in terms of position, appearance and the submucosal course of the
      ureter). RESULTS: Eleven children (18%) presented symptomatic or asymptomatic
      urinary tract infection before the first clinical and radiological review at 2
      months. On the first ultrasound examination, the implant was visualized in the
      bladder wall in 71% of cases. At reimplantation, the bladder mucosa was
      inflammatory in 56 patients (94%). The ureteric orifice remained gaping in 38% of
      cases and the implant appeared to be modified (migration, decreased volume) in
      35% of cases. CONCLUSION: Failures of endoscopic treatment by Macroplastique can
      be due to persistence of pre-existing ureteric anatomical lesions (poor
      indication, technical error or difficulty) or modification of the injected
      product. Bladder inflammation and therefore previous or post-endoscopy urinary
      tract infections may also play a role.

PMID- 15999611
TI  - [Review of the management of enuresis in a Senegalese hospital].
AB  - The profile of enuretic patients consulting a hospital urology department was
      reviewed over a period of 15 months based on 102 cases. The study concerned 47
      male subjects and 55female subjects with a mean age of 15 +/- 5.3 years. The mean
      weekly frequency of enuresis was 5.2 +/- 1.9 and enuresis occurred more than once
      a night for 41.6% of patients. Enuresis was primary in almost 67% of cases.
      Various aetiological factors for enuresis were identified from analysis of the
      clinical data and were generally associated: sleep factor (n=93), bladder factor
      (n=84), hormonalfactor (n=52). Patients were managed as a function of the factors
      identified. With a mean follow-up of 6 +/- 2.1 months, cure was obtained in 30.4%
      of cases and improvement was obtained in 24.5%. The various management problems
      are discussed as a function of socio-economic realities in Senegal and the
      authors emphasize the need for a multifactorial approach.

PMID- 15999612
TI  - [Rupture of the renal artery and renal parenchyma in a pregnant woman with
      vascular form of Ehlers-Danlos syndrome].
AB  - A case of intraparenchymal renal haemorrhage associated with renal artery
      dissection, occurring at the end of pregnancy in a woman with a vascular form of
      Ehlers-Danlos syndrome is reported for the first time. This cases illustrates the
      potential risk of this syndrome and the importance of multidisciplinary
      management to ensure an appropriate diagnostic and therapeutic strategy. Magnetic
      resonance imaging is useful in this setting to elucidate complex cases of renal
      colic in pregnant women presenting an increased risk of ischaemic or haemorrhagic
      disorders.

PMID- 15999613
TI  - [Post-traumatic renal arteriovenous fistula discovered after 28 years].
AB  - There is only one published case of arteriovenous fistula discovered 20 years
      after firearm trauma. The authors report the case of a 47-year-old man injured by
      firearm 28 years ago presenting with a highflow aneurysm of the right renal
      artery secondary to arteriovenous fistula and associated with lower pole renal
      tumour and describe the radiological work-up and surgical management.

PMID- 15999614
TI  - [Renal cell carcinoma secondary to tuberculous nephritis].
AB  - The combination of renal tuberculosis and renal cancer is rare. The authors
      report the case of a patient who was followed for multifocal pulmonary, hepatic
      and renal tuberculosis. The diagnosis of associated renal tumour was raised in
      the presence of suggestive radiological images. Tumourectomy was performed after
      tuberculostatic therapy, and histological examination revealed renal cell
      carcinoma associated with caseo-follicular tuberculous granulomas. The outcome
      was favourable after a follow-up of 2 years. The objective of this study is to
      analyse the pathogenesis, diagnostic features and treatment modalities of this
      exceptional combination.

PMID- 15999615
TI  - [Renal oncocytoma associated with renal cell carcinoma].
AB  - Renal oncocytoma is a benign tumour that can be associated with renal cell
      carcinoma in rare genetic syndromes. The authors report the case of a 62-year-old
      patient with no medical history, in whom assessment of low back pain in 1999
      demonstrated a 40 mm tumour of the lower pole of the left kidney. Percutaneous
      needle biopsy of the tumour demonstrated oncocytoma confirmed by Hale's stain.
      Follow-up ultrasound demonstrated an increase in size (88 mm) and a nine-fold
      increase in volume over four years (210 cm3 in April 2003). Surgery was indicated
      in view of the rapid increase of the tumour volume. Histological examination of
      the operative specimen demonstrated a combination of oncocytoma and Fuhrman grade
      III renal cell carcinoma.

PMID- 15999616
TI  - [Multilocular cystic nephroma in an adult: diagnostic and therapeutic strategy].
AB  - The authors report two clinical cases of cystic nephroma in adults observed in
      the department over the last 10 years. The nonspecific clinical findings and the
      poor contribution of imaging examinations make this rare disease difficult to
      diagnose. Only histological examination can confirm the diagnosis and eliminate
      multilocular cystic renal carcinoma or necrotic pseudocystic carcinoma. Based on
      a review of the literature, the authors emphasize recent pathophysiological and
      immunohistochemical data that could improve the management of this benign
      disease, in which malignant transformation is also possible.

PMID- 15999617
TI  - [Vaginal metastases from renal cell carcinoma].
AB  - Renal cell carcinoma rarely metastasizes to the vagina, as only 80 cases have
      been reported in the literature. Due to the anatomical features of the venous
      drainage of the left kidney, most vaginal metastases are derived from left renal
      tumours. Renal imaging looking for a renal tumour must be performed in the
      presence of a vaginal adenocarcinoma or undifferentiated carcinoma.

PMID- 15999618
TI  - [Angiomyolipoma with epithelioid contingent mimicking renal cell carcinoma].
AB  - The authors report the case of a patient followed for renal angiomyolipoma. On CT
      surveillance, this lesion developed features of a malignant tumour with loss of
      the fatty component and the patient was treated by nephrectomy. Histological
      examination demonstrated renal angiomyolipoma with an epithelioid contingent. The
      various aspects of this histological and radiological variant are discussed.

PMID- 15999619
TI  - [Adult Wilms tumour].
AB  - Wilms tumour is an exceptional tumour in adults. This diagnosis, often
      histological, is generally established at a more advanced clinical stage than in
      children and the prognosis, for the same clinical stage, is comparatively poorer
      in adults. Treatment consists of radical nephrectomy and adjuvant chemotherapy
      and radiotherapy. The authors report a case of Wilms tumour in an adult treated
      by a combination of radical nephrectomy and adjuvant chemotherapy. The patient is
      currently in clinical remission with a follow-up of 2 years.

PMID- 15999620
TI  - [Renal graft rupture].
AB  - Spontaneous rupture of the renal graft is a serious early complication of renal
      transplantation, which can be responsible for loss of the graft. It usually
      follows an episode of acute rejection or acute tubular necrosis. It has a poor
      prognosis, as treatment consists of graft nephrectomy in the majority of cases.
      The authors report a case of renal graft rupture discovered during reoperation
      for severe bleeding. Rupture was secondary to acute tubular necrosis. Treatment
      is designed to preserve the kidney. The outcome was favourable with complete
      recovery of graft function.

PMID- 15999621
TI  - [Small round cell desmoplastic tumour presenting as a testicular mass].
AB  - The authors report a case of small round cell desmoplastic tumour presenting as a
      testicular mass. This is a rare tumour arising from serosal tissues, especially
      the tunica vaginalis. It is characterized by a specific reciprocal translocation
      t(11;22) (p13;q12) inducing fusion of the EWS and WT1 genes. Treatment of this
      tumour consists of a combination of surgical resection, as complete as possible,
      and intensive chemotherapy (P6 protocol or Institut Gustave Roussy protocol) and
      possibly radiotherapy. However, the prognosis remains very poor.

PMID- 15999622
TI  - [Priapism and activated protein C resistance].
AB  - Priapism is a rare disease that can be secondary to a clotting disorder. The
      authors report the first published case of priapism due to a heterozygous
      mutation of factor V Leiden responsible for activated protein C resistance in a
      patient treated with low molecular weight heparin. A similar case has already
      been reported, but with a homozygous mutation. Priapism must therefore be
      considered to be a thromboembolic event and the presence of a clotting disorder
      should be systematically investigated in the absence of an obvious aetiology.

PMID- 15999623
TI  - [Surgical learning curve for creation of vascular accesses for haemodialysis:
      value of medico-radio-surgical collaboration].
AB  - INTRODUCTION: Creation of a vascular access (VA) for haemodialysis is a surgical
      procedure which comprises a failure rate related to the quality of the vessels
      and the operator's experience. The authors report the first 2 years of a young
      urologist's experience with this procedure in a local hospital in collaboration
      with the nephrology team. PATIENTS AND METHODS: Patients undergoing creation of
      VA were divided into 2 chronological groups. The patient's age and gender, the
      cause of renal failure, the presence of diabetes, clinical examination of the
      upper limb, preoperative assessment of upper limb vessels, the type of
      anaesthesia, the operating time and the start of dialysis after the operation, as
      well as the functional results of the VA at 6 months were studied. Results
      concerning the patients of the first period were discussed by the operator and
      the nephrology team. RESULTS: During the first 9 months, 28 patients were
      operated, corresponding to 36 operations including 32 direct fistulas. Over the
      following 15 months, 61 patients were operated, with the creation of 63 VAs,
      including 55 direct fistulas. The failure rate (thrombosis or non-functioning VA)
      decreased from 32.1% to 11.1% (p=0.07), while the 2 groups were globally
      comparable. CONCLUSION: Evaluation of a new surgical procedure shows a number of
      failures, as for all learning curves. However, it helps to improve the results.
      Collaboration with nephrologists must comprise a discussion allowing the
      acceptance of certain failures, as they reflect compliance with a strategy of
      preservation of the vascular capital and a rational attempt to avoid a non
      essential proximal access or bypass graft. The support of a motivated radiology
      team (preoperative assessment and management of complications) and the assistance
      of a more experienced operator are essential.

PMID- 15999624
TI  - [Urology in the work De re medica of Aulus-Cornelius Celsus (1st c. A.D.)].
AB  - The great surgical and urologic attainments of the Greek-Roman period (since
      Hippocrates until August's century) are preserved to us thanks to the work De re
      medica of Celsus of which they constitute the source. Through this paper we
      present the master points of Celsus' urologic work.

PMID- 15999625
TI  - [Greatness and tyranny of modern medicine].

PMID- 15999626
TI  - [Thoughts on the "COX-2 story"].

PMID- 15999627
TI  - [Perioperative pain management at the department of orthopaedic surgery of the
      Vienna Medical School].
AB  - Surgical treatment in the skeleton region and its adjacent tissue causes severe
      pain, demonstrated by the high demand of anaesthetics in the early postoperative
      phase. In order to offer adequate and individually adapted pain management, the
      orthopaedic department is working closely with the departments of anaesthesiology
      and intensive care medicine of the Vienna Medical University at the Vienna's
      General Hospital. The aim of this cooperation is to start postoperative
      rehabilitation early, to increase postoperative quality of life and to reduce the
      length of hospital stay. The surgical spectrum of the orthopaedic department
      consists of general orthopaedic, paediatric-orthopaedic-, sport- and rheuma
      orthopaedic, tumour and spine interventions. The purpose of this review is to
      describe the cooperation between orthopaedic surgeons and anaesthetists at the
      Vienna Medical University.

PMID- 15999628
TI  - [The medical reason for the prescription of COX-2 selective cyclo oxygenase
      inhibitor rofecoxib for the treatment of rheumatoid arthritis. A post-marketing
      surveillance study from Austria].
AB  - This study was designed to analyze reasons why rheumatologists prescribed coxibs
      instead of non-selective NSAIDs in the treatment of rheumatoid arthritis in
      Austria. A simple questionnaire was distributed among interested doctors of
      internal or orthopedic medicine in medical practices treating patients with
      rheumatic diseases. 730 patients with rheumatoid arthritis could be included in
      this study. The argument most often mentioned was the low incidence of
      gastrointestinal side-effects followed by analgesic effectiveness compared with
      non-selective NSAIDs. Easy to use, age of patients and general tolerability were
      further reasons for the decision to prescribe rofecoxib.

PMID- 15999629
TI  - [Direct and indirect costs of rheumatoid arthritis and the socio-emotional
      effects of this disease--an Austrian study].
AB  - The results of this Austrian study confirm the conclusions of earlier studies
      that high costs for the individual and for society result from rheumatoid
      arthritis. We were able to show the figures for direct costs; indirect costs
      could not be calculated in their entirety. Drugs--especially disease-modifying
      drugs--and inpatient treatment constitute the largest percentage of direct costs.
      We describe the enormous psychological and psychosocial impact of rheumatoid
      arthritis, pain, and reduced quality of life. The study also presents a basis for
      the decisions to be made by patients, physicians and health policy makers.

PMID- 15999630
TI  - [Hand injury in polytrauma].
AB  - BACKGROUND: The aim of this study was to evaluate forearm and hand injuries in
      multitrauma patients and to compare this group of patients to the overall
      multitrauma population. PATIENTS AND METHODS: Out of a prospectively gathered
      polytrauma data base a retrospective analysis, including demographics, injury
      severity, injury pattern and treatment of forearm and hand injuries was
      performed. RESULTS: Out of 386 patients (G) that had been entered in our
      polytrauma data base, 26 had forearm and hand injuries (H). The mean age of group
      (H) was 36.4 years (G: 40.3 years, p = 0.220), the mean ISS of this population
      was 28,3 (G: 34.5, p = 0.003). Mostly fractures of the radius (50.0%), the
      metacarpus (53.8%) and the carpus (50.0%) were diagnosed. Surgical interventions
      of hand- and forearm injuries were done in 15 cases within 24 hours, 4 patients
      were treated after 24 hours. CONCLUSION: Multiple trauma patients with hand- and
      forearm injuries showed a statistically significant decreased injury severity and
      were younger compared to the overall multitrauma population.

PMID- 15999631
TI  - [When is a clinical study non-commercial?].
AB  - A non-commercial study is a research project not aiming at the protection of a
      commercial institution's interests. The classification of a clinical study as non
      commercial or commercial makes sense and is important especially for clinical
      research teams, ethics committees and hospital owners because of relevant
      differences in the image and cost fields. The support of non-commercial studies
      by commercial institutions like pharmaceutical companies is permissible, unless
      it is tied to conditions impairing impartiality in respect of design, publication
      of study results or ownership of the assessed data. Specific relationships
      between the investigator and a company of the health industry potentially
      profiting from the study results (e.g. major share holdings or financial
      dependences) favour the classification of a study as commercial. The reliable
      classification of a study as non-commercial is only possible if all aids and
      grants, all conflicts of interest and special agreements are disclosed.

PMID- 15999632
TI  - Does "electromagnetic pollution" cause illness? An inquiry among Austrian general
      practitioners.
AB  - More and more self-declared electromagnetic hypersensitive patients are entering
      physicians' practices seeking help. To assess the prevalence of cases and the
      opinion of Austrian physicians regarding the potential health-relevance of
      environmental electromagnetic fields ("electromagnetic pollution"), a statistical
      investigation among general practitioners was undertaken, with surprising
      results. Only one-third report on never having been asked about the health impact
      of electromagnetic pollution by patients. An overwhelming percentage of general
      practitioners (up to 96%) to some degree, or totally, believe in a health
      relevant role of environmental electromagnetic fields, and only 39% have never
      associated health symptoms with "electromagnetic pollution". Two-thirds are
      consulted occasionally or even frequently by self-declared electromagnetic
      hypersensitive patients. However, sound information seems to be lacking.
      Knowledge on existing electromagnetic exposure limits and on environmental field
      levels in relation to them is poor. It is remarkable that authorities play a
      marginal role in informing physicians. Only 4% mention having received
      information on "electromagnetic pollution" from such a source. It is rather
      remarkable that there is such a widespread contradiction between physicians'
      opinions and established national and international health risk assessment. With
      respect to the frequency with which doctors are confronted with this issue, the
      results demonstrate an urgent need for action.

PMID- 15999633
TI  - [Veterinary education: what are our concerns?].

PMID- 15999634
TI  - [Field study of the prevalence and diagnosis of diarrhea-causing agents in the
      newborn calf in a Swiss veterinary practice area].
AB  - The prevalence of cryptosporidia, rotavirus, bovine coronavirus and Escherichia
      coli F5 (K99) in dairy calves with diarrhea and in healthy calves was established
      in a limited area served by a veterinary practice. Immuno-chromatographic rapid
      tests (FASTest Strips) were applied in the field and their results were compared
      to the ones obtained with standard methods (modified Ziehl-Neelsen stain, antigen
      ELISA and cultivation). In 78% of the calves with diarrhea (n=46) and in 29% of
      the healthy calves (n=14), one or two agents were isolated. Of the diseased
      calves, 43% excreted cryptosporidia and in 46% rotavirus was isolated. Bovine
      corona virus and Escherichia coli F5 (K99) seemed to be of minor importance in
      the investigated population. Compared to the modified Ziehl-Neelsen stain or the
      antigen-ELISA, the FASTest Strips CRYPTO and ROTA were of very high diagnostic
      specificity of 100% each and their diagnostic sensitivity was 75% and 57%,
      respectively. Due to the low number of cases, the results of the FASTest Strips
      BCV and E.coli-K99 could not be interpreted. Although the diagnostic sensitivity
      of the FASTest Strips CRYPTO and ROTA--evaluated with standard methods--was not
      very high, their use in calves with acute diarrhea is recommended.

PMID- 15999635
TI  - [The awareness of farmers with regard to bovine fascioliasis].
AB  - The owners of 54 cattle herds with bovine fasciolosis, as a livestock problem in
      Switzerland, were surveyed on their farm, on their education and knowledge on
      Fasciola hepatica. The aim of the survey was to assess the awareness of the
      farmers concerning this economically important parasitosis. The analysis of the
      questionnaires revealed that 72.2% of the farmers were unaware of the fasciolosis
      in their animals. The knowledge of 51 out of 54 (94.4%) respondents was
      classified as low to moderate, only four farmers (7.4%) had knowledge of control
      strategies in addition to the parasite cycle. The knowledge on fasciolosis did
      not correlate with farm data or year of graduation from school for agriculture.
      Furthermore, the results were compared to the answers of 33 farmers whose animals
      were not infected with Fasciola hepatica. Of this group of respondents 12.1%
      believed that their cattle suffered from fasciolosis.

PMID- 15999636
TI  - [Autochthonous cases of canine babesiosis in the canton Solothurn].
AB  - Starting in November 2003 a series of five clinical cases of canine babesiosis
      was registered in the region of Obergosgen (canton Solothurn). All presented dogs
      showed increased body temperature, thrombocytopenia and hemoglobinuria, and none
      of the dogs had been abroad or visited endemic regions in the southern or western
      part of Switzerland so far. Babesia canis was detected in the blood smears of all
      five patients, but only three had detectable specific antibodies against this
      parasite. However, seroconversion was found in a second sample collected from the
      negative dogs at a later timepoint, confirming the diagnosis of canine
      babesiosis. The blood samples of two parasitized dogs were used for DNA-isolation
      and were tested with a Babesia-specific PCR, detecting the 18S rRNA-gene.
      Sequencing of the amplified products revealed a 100% identity with the sub
      species B. canis canis. The ticks Rhipicephalus sanguineus and Dermacentor
      marginatus are potential vectors for B. canis. In the area where the infection
      with B. canis was suspected a total of 152 ticks was collected and characterized;
      one was a female R. sanguineus.Although babesia could not be detected in the
      latter tick and the final prooffor the complete life cycle is still lacking, it
      is very probable that B. canis has become autochthonous in the canton Solothurn.

PMID- 15999637
TI  - Isolation of Acinetobacter lwoffii from a lovebird (Agapornis roseicollis) with
      severe respiratory symptoms.
AB  - Although Acinetobacter lwoffii is generally considered an ubiquitous and
      opportunistic bacterium, this germ has been isolated from the pulmonary and
      abdominal air sac swabs obtained from a Lovebird (Agapornis roseicollis), which
      died of a severe respiratory disease. Bacteriological tests (phenotypic and
      genotypic) led to the identification of A. lwoffii in pure culture. All the other
      parrots in the breeding centre were treated orally with oxytetracycline for 14
      days and 3 months later no bird showed any signs of respiratory symptoms.

PMID- 15999639
TI  - [Targeted handover in palliative care, to better care...].

PMID- 15999640
TI  - [Storytelling at the heart of nursing, from training to practice].

PMID- 15999642
TI  - [Necessity for a life style change in coronary patients].

PMID- 15999643
TI  - [Dietetics in coronary patients].

PMID- 15999644
TI  - [From smoker to ex-smoker, a new identity].

PMID- 15999645
TI  - [Multislice scanner for coronary arteries].

PMID- 15999646
TI  - [Placement strategy of continuous positive airway pressure].

PMID- 15999647
TI  - [Work delegation and competence transfer, legal approach].

PMID- 15999648
TI  - [Contribution of paramedical personnel in cardiology].

PMID- 15999649
TI  - [The Beaune hospices, a symbol of power and charity].

PMID- 15999656
TI  - [Nutrition in cardiology and diabetology, the case in 2005].

PMID- 15999657
TI  - [Digestive system fistulas, pathogenesis and specific care].

PMID- 15999658
TI  - [Reimbursement/dereimbursement and best practice use of dressings].

PMID- 15999659
TI  - [Clinical aspects of arteriosclerosis obliterans in the lower limbs].

PMID- 15999660
TI  - [Peripheral angioplasty in practice].

PMID- 15999661
TI  - [Arterial bypass techniques].

PMID- 15999662
TI  - [Management of an arteriosclerotic patient with a bypass to the lower limb].

PMID- 15999663
TI  - [Admission of the arteriosclerotic patient in the recovery room and intensive
      care unit].

PMID- 15999664
TI  - [Arterial ulcer dressings, which practice management?].

PMID- 15999665
TI  - [Pain in the arteriosclerotic patient].

PMID- 15999666
TI  - [Dietetic recommendations in vascular cardiology].

PMID- 15999667
TI  - [For a medical treatment of arterial insufficiency].

PMID- 15999668
TI  - [5/6 A driver always in control].

PMID- 15999669
TI  - Factors influencing tumour relapse after total laryngectomy.
AB  - OBJECTIVES: To determine the prognostic factors predictive of tumour recurrence
      after surgical treatment for laryngeal carcinoma with total laryngectomy. STUDY
      DESIGN/METHODS: Retrospective review of 308 patients with laryngeal carcinoma who
      underwent total laryngectomy in the ENT Department of AHEPA University Hospital
      between 01/01/1992 and 31/12/1999. In 238 patients, total laryngectomy was
      performed as primary treatment of laryngeal carcinoma, and in 70 others as
      treatment of tumour recurrence following radiotherapy or partial surgery. Follow
      up was standardized, following a strict protocol, the mean follow-up time was 68
      months. RESULTS: During post-operative follow-up, recurrences were observed in 96
      of 308 patients (31%). The relapse rates were 27% (65 of 238) for patients
      treated with primary total laryngectomy, and 44% (31 of 70) for those treated for
      recurrence following previous treatment. The difference in relapse rates was
      statistically significant. In 39 of 238 (16%) cases treated with primary total
      laryngectomy cervical lymph node infiltration was present at diagnosis and
      radical or modified neck dissection was performed. The tumour recurrence rate in
      this group was 46% (18 of 39), while in metastatic node-free patients the relapse
      rate was 24% (47 of 199) [p < 0.05]. Primary laryngectomy was effective in 82% of
      glottic, 70% of supraglottic, and only 59% of transglottic carcinoma. Concerning
      primary tumour extension at the time of surgery, total laryngectomy proved
      effective in 85% of T2 tumours, 81% of T3, and only 55% for T4. The higher
      recurrence rates for supraglottic and transglottic tumours seem related mainly to
      the higher rates of cervical lymph node metastasis at diagnosis. The majority of
      tumour recurrences were observed during the first two years of post-operative
      follow-up. Thus, 76% of the 308 patients remained disease-free after the first
      year of post-operative follow-up, 68% after the second year, and 67% after the
      fifth follow-up year. Of the 96 recurrences documented until now, 91 were loco
      regional (19 at the tracheostomy), and only 5 involved distant metastases.
      Sixteen of the 308 patients (5%) subjected to total laryngectomy have since
      developed second primary neoplasms, most often involving the lungs (10 patients).
      CONCLUSIONS: Prognostic factors for recurrence following total laryngectomy
      include: performance of total laryngectomy as salvage surgery, degree of tumour
      extension, infiltration of cervical lymph nodes at the time of initial diagnosis,
      poor initial tumour differentiation and trans-glottic/sub-glottic tumour
      localization.

PMID- 15999670
TI  - Performance of two hearing screening protocols in the NICU.
AB  - We recently started a hearing screening program for the newborns of the neonatal
      intensive care unit (NICU) of Shanghai Children's Medical Center. The program
      consisted of a two-step screening stage using DPOAE and automated ABR (AABR) at
      the age of a few days, and a diagnostic stage including otoscopy, measuring
      middle ear impedance and click evoked ABR at the age of two months. Babies who
      were referred on either the basis of DPOAE or DPOAE-AABR screening were referred
      for diagnostic work-up. Of the 200 NICU infants, twenty-nine (14.5%) were
      referred by a single session DPOAE screening. Of these, nine (4.5%) were
      identified by the DPOAE-AABR screening. At the age of two months, six NICU babies
      (3%) had a significant hearing loss based on click-evoked ABR. None of the
      infants who were referred by DPOAE but had passed the AABR screening were found
      to have actual hearing loss. Our study reports the successful implementation of a
      two-step screening protocol for 'at risk' babies in Shanghai. We hope that our
      efforts represent a first step towards the implementation of universal hearing
      screening throughout the People's Republic of China.

PMID- 15999671
TI  - Rehabilitation of high-frequency hearing loss with the RetroX auditory implant.
AB  - The RetroX is a new semi-implantable hearing aid which does not occlude the
      external ear canal. It consists of an electronic unit that plugs into a titanium
      tube which is implanted under the pinna so as to connect the retroauricular
      sulcus with the inside lumen of the external ear canal. Implantation requires
      minor surgery which can be performed under local anesthesia. Moreover, a pre
      implant simulator exists and allows patients to try the device before deciding on
      definite implantation. The RetroX auditory implant is indicated in case of high
      frequency sensorineural hearing loss with a steep slope (ski-slope audiogram). We
      implanted 25 adults suffering from such a hearing loss, and we report their
      hearing measured after 2.5 to 15 months of use. Four patients developed a
      persistent granulomatous reaction which disappeared after explantation. Two
      patients complained of acoustic feedback and needed supplementary fitting. Twenty
      three of our 25 subjects are satisfied or even extremely satisfied with the
      hearing improvement provided by the RetroX; they wear the implant daily, from
      morning until evening. Audiometrically, we observed a statistically significant
      improvement of the pure-tone thresholds at 1, 2, 4 and 8 kHz. In quiet, the
      speech reception thresholds decreased by 10 dB SPL and in noise, speech
      intelligibility increased by 15% for signal-to-noise ratios between -5 dB and +5
      dB. Up till now, our patients were implanted monaurally because of financial
      considerations and our initial inexperience with this new implant. The overall
      results, however, are promising and nowadays, we advise bilateral implantation
      for patients who tolerate the first implant. By doing so, we hope to improve
      hearing in noise and spatial sound perception.

PMID- 15999672
TI  - Chronic maxillary atelectasis.
AB  - Chronic maxillary atelectasis (CMA) is characterized by a reduced maxillary sinus
      volume due to an inward bowing of one or more of the sinus walls. The disorder is
      probably caused by an obstruction of the maxillary ostium, leading to a
      persistent negative pressure within the sinus lumen. To provide insight into the
      epidemiology, pathogenesis and treatment of this disorder, a retrospective study
      of twelve cases that met radiographic criteria of CMA was carried out. The
      patients were equally divided between both sexes and were on average 25 years
      old. Five of the twelve patients were under eighteen years of age. The patients
      had chronic sinonasal complaints except two, who had a "silent sinus syndrome",
      characterized by enophthalmos associated with a marked sinus deformation. This is
      the first report of CMA associated with a benign nasal tumour and also of CMA
      following cicatrisation due to nasal packing for bleeding after endoscopic sinus
      surgery. All patients were treated surgically by creating a middle meatal
      antrostomy, thus restoring sinus ventilation. To conclude, CMA is rare and
      probably underestimated, especially in the paediatric population. Different
      entities causing a complete ostial occlusion can lead to CMA. Endoscopically
      restoring maxillary sinus ventilation is the recommended treatment.

PMID- 15999673
TI  - Risk factors for recurrence of paranasal sinus mucoceles after ESS.
AB  - OBJECTIVE: Paranasal sinus mucoceles are benign, expansive processes filled with
      mucus and bordered by respiratory mucosa. The purpose of our study was to
      determine risk factors for recurrence of mucoceles after endoscopic sinus surgery
      (ESS) based on clinical and radiological characteristics. METHODS: We performed a
      retrospective review of 57 patients consecutively treated endoscopically for
      mucoceles between 1992 and 2002 at the UZ Leuven, a tertiary referral university
      hospital. RESULTS: Paranasal sinus mucoceles predominantly occurred in the
      maxillary sinus and the fronto-ethmoidal region (both 35%). In 69% of patients
      there was a history of sinus surgery (51%) or facial trauma (18%). Recurrence
      occurred in 5 of 49 patients who were treated by ESS in elective circumstances,
      while four of eight patients who underwent ESS at the moment of acute infection
      had recurrence (p = 0.004). Although all recurrences following elective ESS
      occurred in mucoceles related to previous facial trauma or sinus surgery, this
      relationship was not statistically significant (p = 0.2). In three patients,
      significant extension outside the sinus wall was present; three other patients
      had multiple mucoceles. Presence of multiple mucoceles and significant extension
      outside the sinus walls were also risk factors for recurrence (p = 0.002 and p =
      0.001, respectively). In one patient with recurrence, the frontal recess was
      damaged during previous ESS. CONCLUSIONS: Three conditions can be considered risk
      factors for mucocele recurrence after ESS: surgery at a moment of acute
      infection, presence of multiple mucoceles, and significant extension outside the
      sinus wall.

PMID- 15999674
TI  - Osteoma of the sphenoid sinus.
AB  - OBJECTIVE: Only twenty cases of osteomas of the sphenoid sinus have been
      reported. This tumour causes progressively worsening headaches and visual
      disturbance and should be resected when symptomatic or fast-growing. In selected
      cases, endoscopic sinus surgery offers an effective alternative to open
      procedures. CASE REPORT: The authors report a case of sphenoid osteoma in a 19
      year old woman. Computed tomography performed because of complaints of
      progressively worsening headaches identified a large osteoma of the sphenoid
      sinus. The clinical features and radiological assessment of the disease are
      presented together with a review of the literature. RESULTS: The endoscopic
      technique used for resection of the tumour gave a very good result. CONCLUSION:
      Sphenoid osteoma is an extremely rare lesion which can be approached
      endoscopically in selected cases.

PMID- 15999675
TI  - Metastatic renal cell carcinoma to the temporal bone: case report.
AB  - We report an extremely rare case of metastasic renal cell carcinoma to the
      temporal bone which presented initially as a jugulotympanic paraganglioma. The
      clinical and radiological appearances were misleading.Investigations of
      concomitant high blood pressure revealed a tumour of the right kidney. Biopsy of
      the mastoid mass was histologically compatible with a metastasis from a clear
      cell renal carcinoma. The patient underwent a radical nephrectomy and local
      external radiotherapy to the head. He also received adjuvant treatment with
      interferon-_ and interleukin 2. The clinical presentation, the radiological and
      histological features, the patterns of spread, the treatment options and the
      prognosis of these tumours are discussed. A review of the literature confirms the
      extremely unusual occurrence of this localisation.

PMID- 15999676
TI  - Synovial sarcoma of the larynx: case report and literature review.
AB  - Synovial sarcoma is a rare mesenchymal malignancy which represents 8.5% of all
      soft tissue sarcomas and usually occurs in the lower extremities of young adults.
      Because the incidence in the head and neck region is very low, only 13 patients
      with endolaryngeal localisation have been reported so far. We present here a case
      of aryepiglottic synovial sarcoma. The tumour was completely resected, under
      suspension micro-laryngoscopy, using a CO2 laser. No recurrence was observed
      three years after the surgery. Complete surgical excision is the treatment of
      choice. The role of chemotherapy and radiotherapy is still debated. However, this
      tumour has a poor prognosis because of the occurrence of distant metastasis.

PMID- 15999677
TI  - Post-transplant lymphoproliferative disorder with supraglottic involvement.
AB  - OBJECTIVE: Transplant patients with primary Epstein-Barr virus (EBV) infection
      may develop post-transplant lymphoproliferative disorder (PTLD). Since many
      infants are seronegative at the time of transplantation, PTLD is a major concern
      for paediatric transplant centres. First manifestations of PTLD are frequently
      observed in the ENT area with adenoidal and/or tonsillar involvement. DESIGN:
      Retrospective study of two cases of PTLD with confirmed supraglottic involvement,
      their management and outcome. Only patients with pathologically and
      immunologically demonstrated B-cell proliferation were diagnosed as PTLD. RESULT:
      Two infants developed an acute stridor during PTLD respectively 8 and 10 months
      after orthotopic liver transplantation (OLT). These infants were seronegative for
      EBV at the time of transplantation. IgM anti-EBV and/or detection of EBV genome
      by polymerase chain reaction were positive. Laryngeal examination revealed
      hypopharyngeal and/or supraglottic mucosal hyperplasia. Immunostaining of
      laryngeal biopsy was positive for latent membrane protein-1 (LMP1). Patients were
      treated by a reduction in immunosuppression as far as tolerated with the intent
      to recover natural immune response by the patient over the proliferation of EBV
      infected cells. Complete remission of PTLD was observed in these two cases.
      CONCLUSION: Tonsillar hypertrophy and adenoid enlargement are the most
      encountered features of PTLD in OLT occurring in the ENT area. Acute stridor with
      supraglottic involvement may also be observed in PTLD and must be promptly
      diagnosed as the prognosis of this disorder is related to rapid reduction in
      immunosuppression and consequently to the recovering of a natural immune response
      against the EBV infection.

PMID- 15999678
TI  - [Definition and pathobiology of diabetic microangiopathy].

PMID- 15999679
TI  - [Epidemiology of diabetic microangiopathy in Japan with special reference to
      international viewpoint].

PMID- 15999680
TI  - [Prevalence and incidence of diabetic microangiopathy in Japan].

PMID- 15999681
TI  - [EBM on diabetic microangiopathy].

PMID- 15999682
TI  - [Prognosis of diabetic microangiopathy].

PMID- 15999683
TI  - [Assessment of microvascular complication in diabetic subjects].

PMID- 15999684
TI  - [Role of hyperglycemia in the development of diabetic microangiopathy].

PMID- 15999685
TI  - [Role of polyol pathway in pathogenesis of diabetic microangiopathy].

PMID- 15999686
TI  - [AGE-RAGE system in diabetic microangiopathy].

PMID- 15999687
TI  - [Protein kinase C activation and diabetic complications].

PMID- 15999688
TI  - [Role of oxidative stress in pathogenesis of diabetic microangiopathies].

PMID- 15999689
TI  - [Cytokines and microangiopathy].

PMID- 15999690
TI  - [Genetic susceptibility to diabetic microangiopathy].

PMID- 15999691
TI  - [Role of lipid disorders in pathogenesis of diabetic microangiopathy].

PMID- 15999692
TI  - [Role of hypertension in the progression of diabetic microangiopathy].

PMID- 15999693
TI  - [Role of mitochondrial dysfunction in pathogenesis of diabetic microangiopathy].

PMID- 15999694
TI  - [Gene targeting approaches for diabetes research].

PMID- 15999695
TI  - [Progress on the drug therapy for diabetic microangiopathies: aldose reductase
      inhibitor].

PMID- 15999696
TI  - [Progress on the drug therapy for diabetic microangiopathies: AGE inhibitors].

PMID- 15999697
TI  - [Progress on the drug therapy for diabetic microangiopathies: PKCbeta inhibitor].

PMID- 15999698
TI  - [Progress on the drug therapy for diabetic microangiopathies: RA system
      inhibitor].

PMID- 15999699
TI  - [Gene therapy for diabetic microangiopathy].

PMID- 15999700
TI  - [General concept and epidemiology of diabetic retinopathy].

PMID- 15999701
TI  - [Pathology of diabetic retinopathy].

PMID- 15999702
TI  - [International clinical diabetic retinopathy severity scales].

PMID- 15999703
TI  - [Risk factors for incidence and progression of diabetic retinopathy].

PMID- 15999704
TI  - [Retinal circulation].

PMID- 15999705
TI  - [Role of advanced glycation end products and activation of PKC in diabetic
      retinopathy].

PMID- 15999706
TI  - [Role of aldose reductase in the progression of diabetic retinopathies].

PMID- 15999707
TI  - [Roles of cytokines and growth factors in diabetic retinopathy].

PMID- 15999708
TI  - [Fundus-photography and fluorescein-fundus-angiography findings in diabetic
      retinopathy].

PMID- 15999709
TI  - [Measurement of retinal thickness (optical coherence tomography) in patients with
      diabetic retinopathy].

PMID- 15999710
TI  - [Evaluation of retinal circulation in patients with diabetic retinopathy].

PMID- 15999711
TI  - [Analysis of retinal function by electroretinogram in diabetic eyes].

PMID- 15999712
TI  - [Strategies for treatment of diabetic retinopathy].

PMID- 15999713
TI  - [Risk factors of diabetic retinopathy and their control].

PMID- 15999714
TI  - [Potential pharmacological treatments for diabetic retinopathy].

PMID- 15999715
TI  - [Current and future trends in gene therapy for diabetic retinopathies].

PMID- 15999716
TI  - [Retinal photocoagulation for diabetic retinopathies].

PMID- 15999717
TI  - [Vitrectomy for diabetic retinopathy].

PMID- 15999718
TI  - [Fundus findings and pathogenesis of diabetic macular edema].

PMID- 15999719
TI  - [Medications for diabetic macular edema].

PMID- 15999720
TI  - [Surgical management of macular edema].

PMID- 15999721
TI  - [Countermeasures for dropout of diabetic-retinopathy patients by the cooperation
      of physicians].

PMID- 15999722
TI  - [Social support for and social rehabilitation of patients with diabetic
      retinopathy].

PMID- 15999723
TI  - [The Diabetic Retinopathy Candesartan Trials (DIRECT) programme].

PMID- 15999724
TI  - [RNAi and a gene therapy approach to diabetic retinopathies].

PMID- 15999725
TI  - [Concept and epidemiology of diabetic nephropathy].

PMID- 15999726
TI  - [Renal histopathology of diabetic nephropathy].

PMID- 15999727
TI  - [Diabetic nephropathy: diagnostic criteria and staging].

PMID- 15999728
TI  - [Natural history of diabetic nephropathy].

PMID- 15999729
TI  - [Glomerular hyperfiltration in diabetic nephropathy].

PMID- 15999730
TI  - [Dysfunction of mesangial cell and matrix in progression of diabetic
      nephropathies].

PMID- 15999731
TI  - [Mechanisms of diabetic nephropathy--endothelial dysfunction].

PMID- 15999732
TI  - [Microalbuminuria as a biological marker for diagnosis of diabetic
      nephropathies].

PMID- 15999733
TI  - [Urinary N-acetyl-beta-D-glucosaminidase (NAG) in patients with diabetes
      mellitus].

PMID- 15999734
TI  - [Transferrin as a marker for diagnosis of diabetic nephropathies].

PMID- 15999735
TI  - [Urinary type IV collagen as a biological marker for diagnosis of diabetic
      nephropathies].

PMID- 15999736
TI  - [Cystatin C as a biological marker for diagnosis of diabetic nephropathies].

PMID- 15999737
TI  - [Measurement of plasma pentosidine and the clinical significance in diagnosis of
      diabetic nephropathies].

PMID- 15999738
TI  - [Treatment recommendations for various stages in diabetic nephropathy].

PMID- 15999739
TI  - [Treatment of diabetic nephropathy--control of blood glucose].

PMID- 15999740
TI  - [Renoprotective effect of Blood pressure control on progression of diabetic
      retinopathies].

PMID- 15999741
TI  - [Renoprotective effects of ACE inhibitors and AT1 antagonists on diabetic
      nephropathy beyond blood pressure control].

PMID- 15999742
TI  - [Dietary therapy for diabetic nephropathy].

PMID- 15999743
TI  - [Benefits of and contradictions for physical exercise in diabetes and diabetic
      microangiopathy].

PMID- 15999744
TI  - [Recommendation of smoking cessation for diabetic patients].

PMID- 15999745
TI  - [Salt restriction in treatment of diabetes mellitus].

PMID- 15999746
TI  - [Dialysis in diabetic nephropathy].

PMID- 15999747
TI  - [Peritoneal injury and vasculopathy in peritoneal dialysis].

PMID- 15999748
TI  - [Management of diabetic dialysis patients].

PMID- 15999749
TI  - [Cardiovascular complications in diabetic dialysis patients].

PMID- 15999750
TI  - [Kidney transplantation in patients with diabetic nephropathy].

PMID- 15999751
TI  - [Pancreas transplantation and islet transplantation--the effects on diabetic
      microangiopathy].

PMID- 15999752
TI  - [Recent advances in searching the gene(s) conferring susceptibility to diabetic
      nephropathy].

PMID- 15999753
TI  - [Novel therapeutic strategy for diabetic nephropathy].

PMID- 15999754
TI  - [Overview of dialysis therapy for diabetic nephropathies].

PMID- 15999755
TI  - [Concept and epidemiology of diabetic neuropathies].

PMID- 15999756
TI  - [Pathology of diabetic neuropathy].

PMID- 15999757
TI  - [Diagnostic criteria, disease stage, and severity in diabetic neuropathy].

PMID- 15999758
TI  - [Differential diagnosis of diabetic neuropathy--the diabetic polyneuropathy].

PMID- 15999759
TI  - [Nerve flow dynamics in the pathogenesis of diabetic neuropathy].

PMID- 15999760
TI  - [Metabolic factors in the pathogenesis of diabetic neuropathies].

PMID- 15999761
TI  - [Role of cytokine in diabetic neuropathy].

PMID- 15999762
TI  - [Pathogenesis and progression of neuropathies in diabetic patients with
      endothelial dysfunction].

PMID- 15999763
TI  - [Pathophysiological aspects of diabetic polyneuropathy].

PMID- 15999764
TI  - [Hypoglycemia unawareness].

PMID- 15999765
TI  - [Diabetes mellitus and orthostatic intolerance].

PMID- 15999766
TI  - [Digestive disorders in diabetic patients].

PMID- 15999767
TI  - [Bladder dysfunction in diabetics].

PMID- 15999768
TI  - [Erectile dysfunction (ED) and diabetes mellitus].

PMID- 15999769
TI  - [Pupillary dysfunctions in diabetic patients].

PMID- 15999770
TI  - [Sudomotor dysfunction in diabetic patients].

PMID- 15999771
TI  - [Diabetic mononeuropathy].

PMID- 15999772
TI  - [Diabetic central dysfunction].

PMID- 15999773
TI  - [Diabetic amyotrophy].

PMID- 15999774
TI  - [Practical neurological assessments for the diagnosis and staging of diabetic
      polyneuropathy].

PMID- 15999775
TI  - [Sensory function test and Achilles tendon reflex for the diagnosis and staging
      of diabetic neuropathies].

PMID- 15999776
TI  - [Cardiovascular autonomic testing for diagnosis of diabetic autonomic
      neuropathies].

PMID- 15999777
TI  - [Diagnostic tests for gastrointestinal tract in diabetics].

PMID- 15999778
TI  - [Glycemic control and diabetic complications].

PMID- 15999779
TI  - [Symptomatic treatment of painful diabetic neuropathy].

PMID- 15999780
TI  - [Development of therapeutic agents for diabetic neuropathies].

PMID- 15999781
TI  - [Therapeutic vasculogenesis using endothelial progenitor cells for treatment of
      diabetic neuropathies].

PMID- 15999782
TI  - [Angiogenesis therapy by autologous bone marrow cell implantation for diabetic
      foot].

PMID- 15999783
TI  - [Clinical care and education for patients with diabetic polyneuropathy].

PMID- 15999784
TI  - [Early diagnosis of peripheral neuropathy in patients with impaired glucose
      tolerance (IGT)].

PMID- 15999785
TI  - [Role of Ca2+ channels in the pathogenesis of diabetic neuropathy].

PMID- 15999786
TI  - [Diabetic polyneuropathy and ACE gene polymorphism].

PMID- 15999787
TI  - [Stem cells for the treatment of hearing loss].
AB  - One of the greatest challenges in the treatment of inner ear disorders is to find
      a cure for the hearing loss caused by the loss of cochlear hair cells or spiral
      ganglion neurons. The recent discovery of stem cells in the adult inner ear that
      are capable of differentiating into hair cells, as well as the finding that
      embryonic stem cells can be converted into hair cells, raise hope for the future
      development of stem-cell-based treatments.

PMID- 15999788
TI  - [Immediate acoustic effect of the cochlear fistula in a guinen pig].
AB  - INTRODUCTION AND OBJECTIVES: To Evaluate objectively the effect that cochleostomy
      has in the cochlea as well as the exposition of the estria vascularis, through
      acoustic otoemissions immediatly after surgery. MATERIAL AND METHODS:
      Submandibular approach to the guinea pig's middle ear and cochlea. Triming of the
      timpanic and vestibular first turns and wide exposition of the estria vascularis
      in the first and second turns. Study of cochlear function through acoustic
      otoemissions of distortion products. CONCLUSIONS: Guinea Pig is a perfect
      experimentation animal for surgical work when monitoring functional state of the
      cochlea. Its acoustic response is similar to the one found in other mammals thoug
      its response is lower than that reported in other papers. The lack of
      intracochlear manipulation ensures the lower decrease hearing loss deterioration
      regarding the findings in the different methods of studying the acousting
      distortion. RESULTS: There is a decrease of amplitud in the audiograms of
      distortion for specific frequencies (4 and 6 KHz), located tonotopically near the
      cochleostomies carried out in the first turn (at the level of scala vestigularis
      and timpanic). Approadring the cochlea without intracochlear manipulation does
      not modify greathy the results of audiograms of distortion neither the growth
      slopes of the response. A lateral approach of the estric vascularis minimising
      the aggression to labrynth did not cause a significant acoustic deterioration.

PMID- 15999789
TI  - [Stable auditory evoked potentials in the study of two patients with auditory
      neuropathy].
AB  - INTRODUCTION: We described the results of the auditory multiple steady state
      response (MSSR) technique in the assessment of two patients with auditory
      neuropathy (AN). The aim of this study was to corroborate the correspondence
      between the MSSR generators elicited by amplitude modulated tones ranging between
      80-100 Hz, with the generators of auditory brain stem response (ABR). Moreover,
      we would also try to demonstrate the validity of the MSSR in the diagnosis of AN
      in children. MATERIAL AND METHODS: Two children diagnosed of hyperbilirrubinemia,
      aged, 18 months and 10 years have been studied with MSSR (500, 1000, 2000 and
      4000Hz); ABR with clicks; OAE; behavioural audiometry; MRI and acoustic reflexes.
      RESULTS: A difference between electrophysiological and behavioural audiogram in
      both cases diagnosed with auditory neuropathy have been found. The auditory
      thresholds were similar using the two types of evoked potentials (MSSR and ABR).
      Both techniques showed an increment of auditory threshold congruous with a severe
      auditory impairment, while behavioural audiometry showed only a mild elevation of
      auditory threshold. We can also see how the threshold differed between
      frequencies using behavioral audiometry and MSSR. CONCLUSION: It is concluded
      that our findings are in agreement with previous studies and they sustain the
      theory about the coincidence of MSSR at fast rate (80-110 Hz) and ABR generators.
      Also, we demonstrate the usefulness of the MSSR as an objective [corrected]
      electroaudiometric tool in patients with auditory neuropathy as ABR. This
      technique is thus a recommendable test to complete the audiological study in
      infants with AN, to establish a more precise treatment.

PMID- 15999790
TI  - [Speech discrimination through telephone in patients implanted with a Combi 40+].
AB  - OBJECTIVE: To assess speech discrimination through line and mobile telephone in
      cochlear implanted patients. MATERIAL AND METHODS: Eighteen patients implanted
      with a Combi 40+ went through different speech discrimination tests with a line
      telephone and three mobile telephones, in quiet and noisy environment. RESULTS:
      Mean scores for telephonic speech discrimination were 84-92% using CID sentences,
      27-58% using bisyllabic words in quiet environment and 15-41% using bisyllabic
      words in noisy environment. Among the mobile telephones tested, the Siemens M55
      reached the best scores. CONCLUSIONS: Telephonic speech discrimination is
      achieved by a significant number of cochlear implanted patients. Certain mobile
      telephone models appear to be more advisable for these patients.

PMID- 15999791
TI  - [Minimally invasive surgery for treating of complicated fronto-ethmoidal
      sinusitis].
AB  - OBJECTIVES: Functional endoscopic sinus surgery (FESS) is nowadays the "gold
      standard" for frontal sinus pathologies, but management of acute situations and
      the aproach and/or the extent of the surgery perfomed in the frontal recess
      remains controversial nowadays. MATERIAL AND METHODS: We report our experience in
      4 patients with orbital celulitis due to frontal sinusitis who underwent combined
      external surgery (mini-trephination) and endoscopic sinus surgery. RESULTS: All
      patients managed sinus patency without any complications. CONCLUSIONS: We found
      this combined sinusotomy as an easy, effective and reproductible technique in
      order to resolve the difficult surgical management of complicated frontal
      sinusitis.

PMID- 15999792
TI  - [Temporalis myofascial flap: technique description and results in our patients].
AB  - INTRODUCTION: Surgical treatment of intraoral and maxillary sinus carcinomas
      requires a reconstructution of the defect. It is better to do it in one time in
      order to decrease the morbidity for the patient and the sanitary cost. The
      temporalis myofascial flap is used for reconstruction of oral cavity, skull base,
      periorbital region and maxilla because of its feasibility. MATERIAL AND METHODS:
      We describe the surgical technique and present our results of the reconstructions
      after total or partial maxillectomy using the temporalis muscle flap in 22
      patients. RESULTS: No total necrosis of the flap was seen in any case, a partial
      necrosis was seen in four cases. CONCLUSION: The temporalis myofascial flap is an
      excellent choice for oral and maxillary reconstruction.

PMID- 15999793
TI  - [Function vocal examination and acoustic analysis of 905 teaching staff of La
      Rioja, Spain].
AB  - OBJECTIVE: Examination of the vocal function and acoustic analysis in 905
      teachers in La Rioja. DESIGN: A case control study: 576 cases and 329 controls.
      PATIENTS: 905 teaching staff of La Rioja: 589 female and 316 male. METHODS: All
      teachers filled in a standard questionnaire, ENT and vocal function examination,
      videolaryngostroboscopy and acoustic analysis with MDVP. RESULTS: The prevalence
      of voice disorders among teaching staff was 57%. The most prevalent lesions were:
      vocal overeffors (18%) nodular lesions (14%) and hyperfunctional dysphonia (8%).
      The prevalence of vocal symtoms was 79%. A pathological vocal function was found
      more frequent among dysphonic teachers than among normals. Frequency
      perturbations and amplitude perturbations were bigger among dysphonic teachers
      than among normals. Poor correlations were found between algorithms of acoustic
      analisis with MDVP and perceptual evaluation GRBAS. CONCLUSIONS: It is advisable
      to carry out a yearly clinical evaluation of all teaching staff because of the
      high prevalence of voice disorders among them.

PMID- 15999794
TI  - [Cerebro spinal fluid (CSF) leaks in ear: revision of 5 cases].
AB  - CSF leaks in the ear are the result of an abnormal communication between
      subarachnoid and tympano mastoid areas, most of then as a result of trauma (90%).
      They mean a lisk of meningitis (4-50%) directly related to the etiology. Our aim
      is to present the CSF leak cases seen in our hospital in the last 2 years and a
      revision of their management. The main factor for a sucessful surgical repair is
      to use a multilayer tecnhique with a sucess rate close to 100%.

PMID- 15999795
TI  - [Hematoma of the olfactory bulbs following craneoencephalic trauma].
AB  - The ability to smell is commonly altered by head injuries. However, the nature,
      prevalence, prognosis and etiology of such alterations are poorly understood.
      Patients complaining of head-trauma and a related olfactory dysfunction typically
      have anosmia and rarely regain normal olfactory ability. Parosmia prevalences
      decreases over time in such patients, and damage to olfaction-related brain
      structures can be observed in most such patients using an appropriate MRI
      protocol. In this article, we review the recent knowledge about postraumatic
      anosmia.

PMID- 15999796
TI  - [Treatment the secretory otitis with AM3].

PMID- 15999797
TI  - Patterns of genetic variation in humans and mice.
AB  - Positional cloning of genes underlying the heritability of autoimmune disease, as
      in many complex diseases, has largely been a frustrating exercise with few
      replicated positive findings despite enormous efforts at linkage and association
      mapping over the past ten years. Similar difficulties have been encountered by
      researchers attempting to identify such genes in murine models of autoimmunity.
      One reason is the lack of primary knowledge of genetic variation patterns that
      would enable the more efficient design and interpretation of comprehensive
      genetic association studies. We here describe progress towards haplotype maps of
      both the human and mouse genomes including their current application in the
      search for genes underlying autoimmune and inflammatory disorders.

PMID- 15999798
TI  - Haplotype tagging in pharmacogenetics.
AB  - Analyses of variation in human populations have become central to understanding
      how gene variants predispose to disease and influence treatment response. Here I
      first describe an emerging framework for linkage disequilbrium-(haplotype) based
      gene mapping focusing on the analysis of patterns of genetic variation in 56
      genes that metabolize or transport prescription medicines. Detailed analyses of
      754 single nucleotide polymorphisms (SNPs) genotyped in two population samples
      (European and Japanese) provide a set of haplotype tagging SNPs that economically
      represent variation in most of the major enzymes that act on prescription drugs.
      I use these analyses to address a number of outstanding questions relating to
      haplotype mapping. Following this, I provide a number of applications of
      haplotype mapping emphasizing the work that needs to be done to translate
      genotype-phenotype correlations into clinically useful diagnostics, and
      clinically useful leads concerning new therapeutic targets.

PMID- 15999799
TI  - Multiple sclerosis: a haplotype association study.
AB  - Results are presented from a genomewide haplotype association study on multiple
      sclerosis (MS) cases from Tasmania, an island state of Australia. Cases were
      ascertained on strict clinical and radiological grounds and on the fact that they
      had at least one grandparent born in the state. This enriched for early settler
      chromosomes among present day Tasmanians with MS and increased the chances of
      finding common haplotype sharing at disease predisposition loci in distant
      relatives sharing common ancestral haplotypes. Four-to-five close relatives were
      also collected for each of 170 cases and 105 population-based controls. All were
      genotyped at a 5cM resolution, haplotypes reconstructed and sharing estimated
      using an empirical approach based on sorting haplotypes to find the most common
      at each locus and then generating a test statistic for excess sharing in the
      cases based on permutation testing. Five initial loci were found where there was
      an excess sharing in the cases. These were fine-mapped with 10-12 additional
      markers. Only loci on chromosomes 6 and 10 remained after fine mapping. These
      loci demonstrate an increase in sharing of multi-marker haplotypes in MS cases
      compared to both population control transmitted haplotypes and case non
      transmitted haplotypes.

PMID- 15999800
TI  - Mapping genes for asthma and psoriasis.
AB  - A property of susceptibility genes for complex diseases is their reduced
      penetrance, due to the influences of other genes, the environment, or stochastic
      events. With this in mind, it is possible to devise population genetic strategies
      and statistical methods to allow their positional cloning. The identification of
      the relevant effector gene in an implicated locus may provide further challenges
      and require functional studies. The challenges of positional cloning are
      demonstrated by two examples: the cloning of GPRA and AAA1 on chromosome 7p14 at
      a susceptibility locus for asthma and atopy, and the study of HCR on chromosome
      6p21 at PSORS1, the major susceptibility locus for psoriasis. To implicate GPRA
      in asthma and atopy, we studied its isoform-specific expression in bronchial
      biopsies and other sites for allergic reactions. We also studied its expression
      in a mouse model of ovalbumin-induced hypersensitivity. To study the role of HCR
      in psoriasis, we engineered transgenic mice with either a HCR non-risk allele or
      the HCR *WWCC risk allele controlled by the cytokeratin 14 promoter. The results
      suggested that while the overexpression of HCR in mouse skin is insufficient to
      induce a psoriasiform phenotype, it appears to induce allele-specific gene
      expression changes similar to those in psoriatic skin.

PMID- 15999802
TI  - The importance of epistatic interactions in the development of autoimmunity.
AB  - Genetic predisposition is the main element in susceptibility to a variety of
      autoimmune diseases, including systemic lupus erythematosus (SLE). Epistatic
      interactions between susceptibility loci play a major role in the progression of
      autoimmunity, as our recent work, associating a common haplotype of the SLAM/CD2
      receptor family with autoimmune susceptibility in specific genomic contexts, has
      illustrated. Furthermore, these interactions can be abrogated in the presence of
      appropriate modifier loci. We postulate that susceptibility to autoimmunity may
      be a consequence of imbalances in immune regulation that are elicited by specific
      combinations of common alleles at multiple, immunoregulatory loci.

PMID- 15999801
TI  - Natural genetic variants influencing type 1 diabetes in humans and in the NOD
      mouse.
AB  - The understanding of the genetic basis of type 1 diabetes and other autoimmune
      diseases and the application of that knowledge to their treatment, cure and
      eventual prevention has been a difficult goal to reach. Cumulative progress in
      both mouse and human are finally giving way to some successes and significant
      insights have been made in the last few years. Investigators have identified key
      immune tolerance-associated phenotypes in convincingly reliable ways that are
      regulated by specific diabetes-associated chromosomal intervals. The combination
      of positional genetics and functional studies is a powerful approach to the
      identification of downstream molecular events that are causal in disease
      aetiology. In the case of type 1 diabetes, the availability of several animal
      models, especially the NOD mouse, has complemented the efforts to localize human
      genes causing diabetes and has shown that some of the same genes and pathways are
      associated with autoimmunity in both species. There is also growing evidence that
      the initiation or progression of many autoimmune diseases is likely to be
      influenced by some of the same genes.

PMID- 15999803
TI  - Mapping autoimmune disease genes in humans: lessons from IBD and SLE.
AB  - The inflammatory bowel diseases (IBD) and systemic lupus erythematosus (SLE) are
      common autoimmune diseases that affect 2-3 million people in the USA alone.
      Crohn's disease (CD) and ulcerative colitis (UC), the inflammatory bowel
      diseases, are idiopathic, chronic inflammatory disorders of the gastrointestinal
      tract. SLE is a chronic, multi-system autoimmune disease that generally presents
      in women of childbearing age as fatigue, arthralgia and rash. Although the
      aetiology of these two diseases is not fully known, it is believed that genetic,
      hormonal and environmental influences contribute to susceptibility. Genomewide
      linkage scans in IBD have revealed significant loci that, upon comprehensive
      association mapping strategies, yield what are believed to be causal
      susceptibility alleles. Human linkage studies performed to date in SLE have not
      been as informative, although genetic mapping in mouse models of SLE as well as
      candidate gene approaches have provided important clues to the genetic
      susceptibility in humans. We will examine how some of the recent advances in our
      understanding of genetic variation in the human genome are greatly improving our
      ability to map autoimmune disease genes in humans.

PMID- 15999804
TI  - A combined genetics and genomics approach to unravelling molecular pathways in
      coeliac disease.
AB  - Coeliac disease (CD) is a complex, inflammatory disorder of the small intestine
      induced by gluten. It is common and has a prevalence of approximately 1:200 in
      Western populations. A major known susceptibility locus for CD is the HLA -DQ
      locus. However, the genetic contribution of this region is limited to
      approximately 40%, so non-HLA genes must also be involved in the disease
      aetiology. Genetic studies have so far identified multiple loci that may
      potentially be involved in disease aetiology, although the majority of these loci
      are expected to point to genes with a small effect. A major CD locus on
      chromosome 19 was recently identified in the Dutch population. Interestingly,
      there is some marked overlap when comparing genetic linkage studies conducted in
      different autoimmune disorders, suggesting that common pathways contribute to
      these diseases. This knowledge may eventually help in identifying some of the
      disease genes. To identify the true disease-causing genes, linkage analysis needs
      to be followed by genetic association. Because of the nature of the probable
      mutations, it is to be expected that the investigation of gene expression data
      can assist in selecting candidate genes from linkage regions. Furthermore,
      expression data will point to the molecular pathways involved in the disease
      pathogenesis.

PMID- 15999805
TI  - Progress towards understanding the genetic pathogenesis of systemic lupus
      erythematosus.
AB  - In order to better understand the genetic factors that initiate systemic lupus
      erythematosus (SLE), we are using both linkage and association approaches to
      identify susceptibility genes for the disease. Association studies have recently
      identified three HLA Class II haplotypes as well as a functional missense
      polymorphism in protein tyrosine phosphatase (PTP) PTPN22 as important risk
      alleles for SLE. Here, we will review these data, and explain how these findings
      contribute to an understanding of the genetic architecture of human SLE.

PMID- 15999806
TI  - A molecular dissection of lymphocyte unresponsiveness induced by sustained
      calcium signalling.
AB  - In lymphocytes, integration of Ca2+ and other signalling pathways results in
      productive activation, while unopposed Ca2+ signalling leads to decreased
      responsiveness to subsequent stimulation (anergy). The Ca(2+)-regulated
      transcription factor NFAT has an integral role in both aspects of lymphocyte
      function. NFAT cooperates with the transcription factor AP-1 (Fos/Jun) to up
      regulate genes involved in productive activation of lymphocytes. However, in the
      absence of AP-1, NFAT imposes an opposing genetic programme that leads to
      lymphocyte anergy. Anergy is implemented at least partly through proteolytic
      degradation of the key signalling proteins PKCtheta and PLCgamma1. Sustained
      Ca(2+)-calcineurin signalling increases mRNA and protein levels of the E3
      ubiquitin ligases Itch, CblB and Grail and induces expression of Tsg1O1, the
      ubiquitin-binding component of the ESCRT1 endosomal sorting complex. Subsequent
      stimulation or homotypic cell adhesion promotes membrane translocation of Itch
      and the related protein Nedd4, resulting in PKCtheta and PLCgamma1 degradation. T
      cells from Itch- and CblB-deficient mice are resistant to anergy induction.
      Anergic T cells show impaired calcium mobilization after TCR triggering and are
      unable to maintain a mature immunological synapse. Thus Ca(2+)-calcineurin-NFAT
      signalling links gene transcription to a multi-step programme that leads to
      impaired signal transduction in anergic T cells.

PMID- 15999807
TI  - Genetic lesions in thymic T cell clonal deletion and thresholds for autoimmunity.
AB  - The cause of common polygenic autoimmune diseases is poorly understood because of
      genetic and cellular complexity in humans and animals. We have investigated the
      mechanisms of two genetic causes of organ-specific autoimmunity by tracking the
      fate of high avidity organ-specific CD4 T cells using a transgenic mouse model.
      Firstly, we have found that an Idd-associated duster of loci from the NOD strain
      causes a T cell intrinsic failure to delete during in vivo encounter with high
      avidity autoantigen, a trait distinguished by the failure to induce the pro
      apoptotic gene Bim. Secondly, we have found that inactivation of the autoimmune
      regulator (Aire) gene reduces the level of thymic expression of organ-specific
      genes, in a gene-dose dependent manner. In this paper we describe a model
      relating efficiency of thymic deletion and susceptibility to autoimmunity. Using
      this model, subtle quantitative trait loci can have an additive effect on each of
      the parameters of thymic deletion, and the result of interaction between subtle
      modifications in the multiple parameters can result in large changes in the
      susceptibility to autoimmunity.

PMID- 15999808
TI  - An autoimmune disease-associated CTLA4 splice variant lacking the B7 binding
      domain signals negatively in T cells.
AB  - Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) plays a critical role in down
      regulating T cell responses. A number of autoimmune diseases have shown genetic
      linkage to the CTLA4 locus. We have cloned and expressed an alternatively spliced
      form of CTLA4 that has genetic linkage with type 1 diabetes in NOD mice. This
      splice variant of CTLA4, named ligand-independent CTLA4 (liCTLA4), lacks exon 2
      including the MYPPPY motif essential for binding to the costimulatory ligands B7
      1 and B7-2. liCTLA4 is expressed as a protein in primary T cells and strongly
      inhibits T cell responses by binding and dephosphorylating the TcRzeta chain.
      Expression of liCTLA4, but not full length CTLA4 (flCTLA4), was higher in
      memory/regulatory T cells from diabetes resistant NOD congenic mice compared to
      susceptible NOD mice. Transgenic expression of liCTLA4 in autoimmune prone Ctla4 
      /- mice inhibited spontaneous T cell activation and prevented early lethality in
      the Ctla4 -/- mice. Thus, increased expression and negative signalling delivered
      by the liCTLA4 may play a critical role in regulating the development of T cell
      mediated autoimmune diseases.

PMID- 15999810
TI  - Genomic mining of new genes and pathways in innate and adaptive immunity.
AB  - Plant disease resistant (R) genes constitute a large family that mediates host
      response to bacteria, viruses and fungi. Large mammalian proteins containing a
      nucleotide binding domain (NBD) and C-terminal leucine-rich repeats (LRRs) are
      similar in structure to the TLR/NBD/LRR subfamily of R proteins and have been
      suggested as a link between innate and acquired immunity. Because of our long
      term interest in one of these, the class II transactivator (CIITA), and recent
      reports linking mutations in two new NBD/LRR proteins (Nod2/CARD 15 and CIAS
      1/cryopyrin) to various autoimmune and inflammatory disorders, we have performed
      a comprehensive search of the human genome and found a multigene family which we
      termed the CATERPILLAR (CARD, Transcription Enhancer, R[purine]-binding, Pyrin,
      Lots of Leucine Regions)family. The N-termini of these genes are varied although
      the majority have a pyrin domain and few have a CARD domain. The genomic
      organization of these genes demonstrates a high degree of conservation with the
      NBD encoded as a single large exon and the LRRs encoded in two basic
      arrangements. Detailed analysis and new functional data regarding a number of the
      CATERPILLAR proteins will be described, including CIITA, cryopyrin and Monarch 1.

PMID- 15999809
TI  - Large-scale screens for cDNAs with in vivo activity.
AB  - The pace of biological investigation has been greatly accelerated by technologies
      that permit comprehensive inventory of gene expression under diverse conditions.
      We have been developing and using approaches to understand gene function that are
      based on functional assessments of gene activity, using automated expression
      cloning followed by gene knockdown using shRNA or by gene knockout. Some recent
      developments in expression screens and methods to expedite the formation of
      targeted mutations in mice are discussed. A resource for large scale quantitative
      profiling of mRNA abundance is also described.

PMID- 15999811
TI  - Effect of thallium ions on isolated mitochondria of rat liver in the presence of
      nonactin.

PMID- 15999812
TI  - Discovery of retrotransposons of the cockroach Blattella germanica.

PMID- 15999813
TI  - The role of bioflavonoids and their complexes with metals in stabilization of
      wood under natural conditions.

PMID- 15999814
TI  - Two-hybrid yeast test system for assessment of estrogenic activity of chemical
      compounds.

PMID- 15999815
TI  - New types of luminescent systems of soil enchytraeids (Annelida: Clitellata:
      Oligochaeta: Enchytraeidae).

PMID- 15999816
TI  - A new approach to obtaining deoxyribo- and ribonucleoside 5'-mono- and
      triphosphates.

PMID- 15999817
TI  - Heterochromatic stellate repeats of Drosophila and the reporter gene silencing in
      the yeast Saccharomyces cerevisiae.

PMID- 15999818
TI  - Genetic identification of mosquitoes of the group Culex pipiens (Diptera:
      Culicidae) by RAPD analysis.

PMID- 15999819
TI  - Effect of plasmalemma electrical excitation on photosystem II activity and
      nonphotochemical quenching in chloroplasts of cell domains in Chara corallina.

PMID- 15999820
TI  - Lipoplexes based on cholesterol derivatives of oligo (ethylene propylene imines)
      in gene transfer in vitro and in vivo.

PMID- 15999821
TI  - Melamine salt of bis(methylol)phosphinic acid (melaphene) as a regulator of
      Rauwolfia serpentina specialized metabolism.

PMID- 15999822
TI  - Spin and magnetic effects in biological systems are the privilege of membrane
      phospholipids.

PMID- 15999823
TI  - Study of biochemical mechanism of action and toxic properties of a zinc
      containing derivative of chlorophyll.

PMID- 15999824
TI  - A glycolipid containing a lactose residue: a novel agent for targeted DNA
      delivery for the purpose of genetic therapy.

PMID- 15999825
TI  - The effect of ladasten on gene expression in the rat brain.

PMID- 15999826
TI  - Synthesis of functionally active human proinsulin in a cell-free translation
      system.

PMID- 15999827
TI  - Electric and viscoelastic properties of erythrocytes of patients with diffuse
      pathology of the liver.

PMID- 15999828
TI  - Nonenzymatic template-dependent ligation of 2',3'-cyclic phosphate-containing
      oligonucleotides catalyzed by metal ions.

PMID- 15999829
TI  - Study of immunogenic properties of the candidate edible vaccine against human
      immunodeficiency and hepatitis B viruses based on transgenic tomato fruits.

PMID- 15999830
TI  - The molecular weight of Cl-, HCO3(-)-activated Mg(2+)-ATPase of rat brain plasma
      membranes that is sensitive to GABAA-ergic ligands.

PMID- 15999831
TI  - Regulation of oxidative potential of neutrophils by reproductive hormones depends
      on the level of cell activation.

PMID- 15999832
TI  - Molecular mechanisms of the regulatory effect of biogenic amines on the
      functional activity of the adenylate cyclase signal system in nerve ganglia of
      the mollusk Anodonta cygnea.

PMID- 15999833
TI  - [Informing patients on the risk of malaria].

PMID- 15999834
TI  - [Sudden infant death syndrome: is the problem solved?].

PMID- 15999835
TI  - [Guillain-Barre syndrome].
AB  - The annual incidence of Guillain-Barre Syndrome is 1.5 per 100000 people. It has
      an associated mortality of about 5%, with ten percent of patients severely
      disabled one year after the first onset of neurological signs. To treat this
      condition, specialist teams, access to intensive care and rehabilitation are
      essential and should be provided in appropriate hospital units. Neither oral nor
      intravenous corticosteroids are beneficial. Plasma exchange (PE) is the first
      line treatment having been found to improve outcomes in several randomised,
      controlled clinical trials. The indications for treatment have now been
      clarified. Two PE are recommended in patients who are able to walk (mild) with
      two additional PE if they deteriorate. In patients unable to walk unaided
      (moderate), four plasma exchanges are sufficient, likewise in those who require
      mechanically ventilation (severe form). It is not useful to add further PE in
      more severe disease or if there is no response. High-dose of intravenous
      immunoglobulin (0.4 g/kg daily for 5 days) and PE are equally effective in
      intermediate and severe forms. The choice between the two treatments depends on
      their respective contra-indications and local availability. A trial is underway
      to assess the indications and optimal dose of IVIg and number of PE to be used in
      different severities of disease.

PMID- 15999836
TI  - [Malaria: no shortage of patients but the market is failing].

PMID- 15999837
TI  - [Epidemiology of malaria].
AB  - Four parasite species, among which one lethal, at least 20 efficient vectors,
      spread on the most crowded and underdeveloped continents, where first
      antimalarials and insecticides were so extensively used for decades that they are
      now inefficient after resistances. It is today the sad medium on which malaria
      raged, spring of 1 million deaths and 300 millions cases a year, of which 90% in
      sub-Saharan Africa. In Africa, epidemiological patterns are widely different some
      to others, which explain unique control strategy failure and vanity. Waiting
      vaccines and new drugs, control must be centred on vectors control and multidrug
      therapy. France is the industrialised country with the highest number of imported
      cases (approximately equal to 7000 cases yearly), linked mainly to P. falciparum
      coming from sub-Saharan Africa and recurring in nearly 3/4 of cases in
      immigrants.

PMID- 15999838
TI  - [Malaria: what about exposure prophylaxis?].
AB  - Malaria would not exist without mosquito bites. The growing resistance to
      antimalarial drugs has led to an increasing role of personal protection measures.
      However, insect repellents are not evaluated as medicinal products, and many
      products available on the market contain active substances that have been poorly
      evaluated or present in insufficient doses. The efficacy of the most active
      insect repellents, DEET and icaridin/KBR 3023, like that of medicinal products,
      is limited by the subject's compliance, bearing in mind that the Anopheles bite
      is painless and that humans are primarily bothered by the nuisance factor of the
      mosquito.

PMID- 15999839
TI  - [Malaria chemoprophylaxis in 2005: new policy, new drugs].
AB  - For a traveller visiting highly endemic areas for malaria (mainly sub-Saharan
      Africa), the use of a chemoprophylaxis has to be considered as mandatory in
      addition to exposure prophylaxis measures (including in migrants largely over
      represented among returning travellers with imported malaria). The choice of the
      appropriate drug depends mainly on the visited area with regard to the level of
      resistance to chloroquine. Due to the spread of resistance, 7 countries along the
      West African coast between Senegal and Cote d'Ivoire moved in 2005 from zone 2 to
      zone 3 (according to the French classification). Recently available and
      recommanded in zones 2 and 3, the atovaquone+proguanil combination appears to be
      of great interest due to a good tolerance and an intake limited to the 7 days
      following return. Alternatively to mefloquine or atovaquone+proguanil, the well
      tolerated and cheap doxycycline is a good choice but due to its short half life a
      full compliance is mandatory. In case of fever, even if a chemoprophylaxis is
      taken, malaria can develop, sometimes with atypical presentations, and has to be
      systematically considered.

PMID- 15999840
TI  - [Diagnosis and management of imported malaria].
AB  - Any fever in a traveller returning from a tropical area has to be considered
      first as a malaria attack and needs a parasitological diagnosis. Nevertheless,
      physicians have to be aware of atypical presentations (lack of fever, febrile
      enteritis, false negative smear...). In non-falciparum malaria, chloroquine
      remains the drug of choice. In falciparum-malaria, an ambulatory treatment by the
      association atovaquone-proguanil or oral quinine is possible only if certain
      criteria are respected. On the opposite, only one sign of severity (including
      mild consciousness disorders) implies a transfer in an intensive care unit for
      emergency treatment with IV quinine including a loading dose. A follow-up with
      clinical and parasitological assessment at D3, D7 and D28-35 is an important
      aspect in the management of a malaria case.

PMID- 15999841
TI  - [The future outlook of antimalarials].
AB  - Spreading of resistance to chloroquine in the early 1960's had a dramatic impact
      on malaria treatment worldwide. The development of new antimalarial drugs, at
      first driven by political interests, is now centred on the need to limit disease
      extension due to a strong sensibilisation by NGO and the medias. Difficulties in
      using antimalarial drugs are mostly the result of geographic variabilities of
      drug resistance of Plasmodium falciparum to existing drugs, implying a decision
      "a la carte" for malaria treatment in each endemic country. To fight against
      resistance situations, the NGO Medecins sans frontieres and the World Health
      Organization have launched the concept of multiple antimalarial drug therapies
      based on artemisinin derivatives. Such strategy has been initiated in order to
      limit extension of drug resistance to existing antimalarial treatments, waiting
      for a new innovative drug able to provide a "universal" treatment worldwide which
      does not exist at present.

PMID- 15999842
TI  - [Repellents, anopheles, and prevention of malaria].

PMID- 15999843
TI  - [New national ranking examination and medical workforce].

PMID- 15999844
TI  - [Vulnerable populations: risk factors and evaluation. Measures of protection].

PMID- 15999845
TI  - [Weight loss].

PMID- 15999846
TI  - [Customised treatment decisions: drug therapy].

PMID- 15999847
TI  - [Chronic glaucoma].

PMID- 15999848
TI  - [Micro-crystalline arthropathy].

PMID- 15999849
TI  - [Louis Hubert Farabeuf (1841-1910). A famous master in practical anatomy and
      surgery education].

PMID- 15999850
TI  - Solid-state fermentation systems-an overview.
AB  - Starting with a brief history of solid-state fermentation (SSF), major aspects of
      SSF are reviewed, which include factors affecting SSF, biomass, fermentors,
      modeling, industrial microbial enzymes, organic acids, secondary metabolites, and
      bioremediation. Physico-chemical and environmental factors such as inoculum type,
      moisture and water activity, pH, temperature, substrate, particle size, aeration
      and agitation, nutritional factors, and oxygen and carbon dioxide affecting SSF
      are reviewed. The advantages of SSF over Submerged Fermentation (SmF) are
      indicated, and the different types of fermentors used in SSF described. The
      economic feasibilities of adopting SSF technology in the commercial production of
      industrial enzymes such as amylases, cellulases, xylanase, proteases, phytases,
      lipases, etc., organic acids such as citric acid and lactic acid, and secondary
      metabolites such as gibberellic acid, ergot alkaloids, and antibiotics such as
      penicillin, cyclosporin, cephamycin and tetracyclines are highlighted. The
      relevance of applying SSF technology in the production of mycotoxins, biofuels,
      and biocontrol agents is discussed, and the need for adopting SSF technology in
      bioremediation of toxic compounds, biological detoxication of agro-industrial
      residues, and biotransformation of agro-products and residues is emphasized.

PMID- 15999851
TI  - Knowledge discovery in biology and biotechnology texts: a review of techniques,
      evaluation strategies, and applications.
AB  - Arguably, the richest source of knowledge (as opposed to fact and data
      collections) about biology and biotechnology is captured in natural-language
      documents such as technical reports, conference proceedings and research
      articles. The automatic exploitation of this rich knowledge base for decision
      making, hypothesis management (generation and testing) and knowledge discovery
      constitutes a formidable challenge. Recently, a set of technologies collectively
      referred to as knowledge discovery in text (KDT) has been advocated as a
      promising approach to tackle this challenge. KDT comprises three main tasks:
      information retrieval, information extraction and text mining. These tasks are
      the focus of much recent scientific research and many algorithms have been
      developed and applied to documents and text in biology and biotechnology. This
      article introduces the basic concepts of KDT, provides an overview of some of
      these efforts in the field of bioscience and biotechnology, and presents a
      framework of commonly used techniques for evaluating KDT methods, tools and
      systems.

PMID- 15999852
TI  - Biofiltration of air: a review.
AB  - In this paper we present a review of the existing air pollution control
      technologies (APCT), when used essentially for the elimination of volatile
      organic compounds (VOC). The biotechnologies referred to, bioscrubbers,
      biotrickling filters and biofilters, are also described. A more detailed review
      of biofiltration is proposed, presenting the most recent and latest developments
      achieved in the field of bioprocessing. In particular, the influence of the
      filter bed, the polluted air flowrates, the pollutants, the pressure drop, bed
      moisture content, temperature, nutrients, pH and the microorganisms are reviewed.
      Models of biofiltration are also presented.

PMID- 15999853
TI  - Embracing diversity to overcome health disparities.

PMID- 15999854
TI  - Culturally competent rehabilitation nursing.

PMID- 15999855
TI  - Mini-rounds: a team communication tool.

PMID- 15999856
TI  - How do we assess the learning style of our patients?

PMID- 15999857
TI  - Rehabilitation nurses working as collaborative research teams.
AB  - Rehabilitation nurses conducting research would benefit from working within
      collaborative research teams. The development of intradisciplinary (one
      discipline) and interdisciplinary (many disciplines) research teams is described
      in this article. A research team is defined as more than a single person in the
      role of the researcher while studying the same topic of interest in a joint or
      collaborative manner. Strategies to ensure successful research team collaboration
      are described. Exemplars of developing and maintaining a team at one site, which
      consists of members of the same discipline, as well as another team that consists
      of multiple professional disciplines, are shared. Collaboration among research
      team members in practice, administration, and education settings transcends
      degrees and roles to make substantial contributions to professional practice.

PMID- 15999858
TI  - Patient-provider communication regarding referral to cardiac rehabilitation.
AB  - This study investigated the dynamics of patient-provider communication in the
      cardiac rehabilitation (CR) referral process, to identify which aspects lead to
      CR participation. Semi-structured individual interviews were conducted with 31
      patients eligible for CR. Questions probed the content and perception of the
      discussion that patients had with healthcare providers (HCP) regarding CR
      attendance. The interviews were audiotaped, transcribed, and imported into N6
      software for grounded analyses. Key emerging themes were identified: illness
      perceptions; HCP encouragement; timing of discussion; and ease of referral. CR
      attenders were apt to self-advocate to ensure their enrollment in CR, whereas
      nonattenders were more likely to minimize the seriousness of their disease, and
      less likely to persevere to overcome obstacles in enrolling in a CR program.
      Surprisingly, the strength of the HCP referral did not influence the decision to
      attend CR as strongly when compared to the HCP's ability to facilitate enrollment
      in a CR program.

PMID- 15999859
TI  - Self-organization in chronic pain: a concept analysis.
AB  - The purpose of this article is to examine the concept of self-organization in
      chronic pain using Rodgers' (2000) evolutionary approach. This article describes
      the antecedents, attributes, and consequences of self-organization in chronic
      pain. Self-organization in chronic pain may be achieved through the attributes of
      being believed, accessing credible resources, and taking action and
      responsibility. Self-organization occurs when the patient with pain develops a
      transformed identity, new insights, and is an active, in-control participant in
      care. Chronic pain is a common and costly problem, and recognition of the key
      attributes of self-organization in this condition is an important step in
      promoting positive health outcomes. Rehabilitation nurses play a key role in
      providing credible resources and working with the patient to take action and
      responsibility.

PMID- 15999860
TI  - Adult failure to thrive in the older rehabilitation patient.
AB  - Increasing numbers of older adults require rehabilitation therapy upon discharge
      from a hospital. This pilot study tested a tool developed to assess failure to
      thrive syndrome (FTT) in patients admitted to a long-term rehabilitation unit (N
      = 34), examined the association among commonly recognized FTT factors
      (persistent, unexpected impairment in physical function, cognitive impairment,
      and poor nutrition and mood state), and investigated relationships between FTT
      factors and discharge disposition. Patients with a high level of physical
      function differed from those with a low level of function in terms of age, mood
      state, and discharge disposition. Patients discharged home differed from patients
      who were unable to return home in mood state, physical function score, and
      admission serum albumin. Suggestions for practice and further research are
      offered.

PMID- 15999861
TI  - Evidence-based clinical improvement for mechanically ventilated patients.
AB  - Bundling or grouping together evidence-based interventions to improve care for
      the mechanically ventilated patient was piloted by a 10-bed medical-surgical
      critical care unit of a hospital. The bundled care interventions included: (a)
      keeping the head of bed elevated at 30 degrees, (b) instituting daily
      interruption of continuous sedative infusion, (c) assessing readiness to wean
      using a rapid-wean assessment guide, (d) initiating deep venous thrombosis
      prophylaxis, and (e) implementing peptic ulcer disease prophylaxis. The
      interventions were implemented using a plan-do-check-act quality-improvement
      methodology. Results indicated that the use of bundled interventions for
      mechanically ventilated patients could decrease average ventilator times and
      average length of stay with no concomitant increase in reintubations. Average
      mortality rates and the number of adverse events per 100 patient days also were
      reduced.

PMID- 15999862
TI  - The family physician workforce: quality, not quantity.

PMID- 15999863
TI  - Advise sexually active patients to consider HIV testing.

PMID- 15999864
TI  - Travel immunizations: benefits and precautions.

PMID- 15999865
TI  - Family physicians and the primary care physicians workforce in 2004.
AB  - In 2004, there were 91,600 family physicians (FPs) and general practitioners
      (GPs) and 222,000 primary care physicians actively caring for patients, one for
      every 1321 persons. These primary care physicians represent the largest and best
      trained primary care physician workforce that has ever existed in the United
      States.

PMID- 15999866
TI  - Secondary prevention of coronary heart disease in elderly patients.
AB  - Coronary heart disease remains a leading cause of mortality in the United States,
      with 84 percent of persons 65 years or older dying from this disease. Secondary
      preventive measures, including lifestyle modification and pharmacotherapy, are
      important for elderly patients because of the variable impacts on morbidity and
      mortality rates and quality of life. Participating in light to moderate
      activities significantly decreases mortality rates in elderly patients. Smoking
      cessation translates into a reduction in overall mortality and morbidity rates at
      least equal to that of other preventive measures such as aspirin or beta-blocker
      therapy. Recent studies on the effects of lowering low-density lipoprotein
      cholesterol levels to below 100 mg per dL have shown a substantial reduction in
      coronary heart disease mortality and nonfatal myocardial infarction rates, with a
      persistent effect in patients older than 75 years. Hypertension, manifesting
      mostly as isolated systolic blood pressure elevation, also should be treated
      aggressively. Conventional medical therapies for hypertension (e.g., diuretics,
      beta blockers) and newer agents (e.g., calcium channel blockers, angiotensin
      converting enzyme inhibitors), together with sodium restriction, have had a
      positive effect on cardiovascular mortality and morbidity rates in older
      patients. With the increasing prevalence of obesity, insulin resistance, and type
      2 diabetes, interventions targeting weight reduction and glucose control should
      be emphasized. Whereas weight-loss strategies are poorly defined in this
      population, the management of diabetes through dietary modification, exercise,
      and medications is similar across age groups. The target hemoglobin A1C level is
      less than 7 percent. Elderly patients are prone to depression and social
      isolation, and they are more likely to have a lower socioeconomic status than
      younger patients, which may negatively affect participation in rehabilitation
      programs and compliance with medical advice and therapy. Strategies aimed at
      these factors have shown variable results and remain ill-defined.

PMID- 15999867
TI  - Evaluation and management of apparent life-threatening events in children.
AB  - Apparent life-threatening event syndrome predominantly affects children younger
      than one year. This syndrome is characterized by a frightening constellation of
      symptoms in which the child exhibits some combination of apnea, change in color,
      change in muscle tone, coughing, or gagging. Approximately 50 percent of these
      children are diagnosed with an underlying condition that explains the apparent
      life-threatening event. Commonly, the problems are digestive (up to 50 percent),
      neurologic (30 percent), respiratory (20 percent), cardiac (5 percent), and
      endocrine or metabolic (less than 5 percent). Fifty percent of these events are
      idiopathic, which causes great concern to parents and physicians. The evaluation
      of an affected infant involves a thorough description of the event as well as
      prenatal, birth, medical, social, and family history. The physical examination,
      including careful neurologic examination and notation of any apparent anatomic
      abnormalities, helps diagnose congenital problems, infection, and conditions
      contributing to respiratory compromise. The laboratory evaluation is driven by
      historical and physical findings. Inpatient evaluation and monitoring are
      recommended in virtually all cases unless investigations are normal. Should the
      history reflect a severe episode, or should the child require major interventions
      such as cardiopulmonary resuscitation, inpatient observation and monitoring are
      recommended, even if physical examination and laboratory findings are normal.
      Once a presumptive diagnosis is made, events should cease after appropriate
      intervention. If not, reviewing the history, performing another physical
      examination, and reassessing the need for laboratory and imaging studies are the
      next steps. Although consensus statements by the National Institutes of Health
      and the American Academy of Pediatrics support home monitoring, the relationship
      of apparent life-threatening event syndrome to sudden infant death syndrome is
      controversial.

PMID- 15999868
TI  - Health issues for surfers.
AB  - Surfers are prone to acute injuries as well as conditions resulting from chronic
      environmental exposure. Sprains, lacerations, strains, and fractures are the most
      common types of trauma. Injury from the rider's own surfboard may be the
      prevailing mechanism. Minor wound infections can be treated on an outpatient
      basis with ciprofloxacin or trimethoprim-sulfamethoxazole. Jellyfish stings are
      common and may be treated with heat application. Other treatment regimens have
      had mixed results. Seabather's eruption is a pruritic skin reaction caused by
      exposure to nematocyst-containing coelenterate larvae. Additional surfing hazards
      include stingrays, coral reefs, and, occasionally, sharks. Otologic sequelae of
      surfing include auditory exostoses, tympanic membrane rupture, and otitis
      externa. Sun exposure and skin cancer risk are inherent dangers of this sport.

PMID- 15999869
TI  - Information from your family doctor. Safe surfing.

PMID- 15999870
TI  - Tick-borne disease.
AB  - Tick-borne diseases in the United States include Rocky Mountain spotted fever,
      Lyme disease, ehrlichiosis, tularemia, babesiosis, Colorado tick fever, and
      relapsing fever. It is important for family physicians to consider these
      illnesses when patients present with influenza-like symptoms. A petechial rash
      initially affecting the palms and soles of the feet is associated with Rocky
      Mountain spotted fever, whereas erythema migrans (annular macule with central
      clearing) is associated with Lyme disease. Various other rashes or skin lesions
      accompanied by fever and influenza-like illness also may signal the presence of a
      tick-borne disease. Early, accurate diagnosis allows treatment that may help
      prevent significant morbidity and possible mortality. Because 24 to 48 hours of
      attachment to the host are required for infection to occur, early removal can
      help prevent disease. Treatment with doxycycline or tetracycline is indicated for
      Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, and relapsing fever. In
      patients with clinical findings suggestive of tick-borne disease, treatment
      should not be delayed for laboratory confirmation. If no symptoms follow exposure
      to tick bites, empiric treatment is not indicated. The same tick may harbor
      different infectious pathogens and transmit several with one bite. Advising
      patients about prevention of tick bites, especially in the summer months, may
      help prevent exposure to dangerous vector-borne diseases.

PMID- 15999871
TI  - Information from your family doctor. Ticks--how to protect yourself.

PMID- 15999872
TI  - Primary care interventions to prevent low back pain in adults: recommendation
      statement.

PMID- 15999873
TI  - Choosing between warfarin (Coumadin) and aspirin therapy for patients with atrial
      fibrillation.

PMID- 15999874
TI  - A healthy woman with right upper quadrant discomfort on deep palpation.

PMID- 15999875
TI  - Eszopiclone (Lunesta) for treatment of transient and chronic insomnia.

PMID- 15999876
TI  - The impaired physician.

PMID- 15999877
TI  - Changes in some liver enzymes in streptozotocin-induced diabetic rats fed
      sapogenin extract from bitter yam (Dioscorea polygonoides) or commercial
      diosgenin.
AB  - The effects of steroidal sapogenin extract from bitter yam or commercial
      diosgenin on liver enzyme changes were investigated Diabetic male Wistar rats
      were fed diets supplemented with 1% steroidal sapogenin extract or commercial
      diosgenin for three weeks. Plasma glucose levels and the activities of hepatic
      glucose-6-phosphatase, pyruvate kinase and glucose-6-phosphate dehydrogenase were
      assessed Liver total cholesterol, HDL-cholesterol and total phospholipid were
      also measured. Plasma glucose decreased significantly (p < 0.05) in diabetic rats
      fed the three test diets compared to the diabetic control. The three test diets
      significantly decreased glucose-6-phosphatase activity compared to the diabetic
      control The activities of ATP-citrate lyase, pyruvate kinase and glucose-6
      phosphate dehydrogenase were significantly reduced in the liver of diabetic rats
      compared to normal control. Supplementation of the diet with bitter yam steroidal
      sapogenin extract or commercial diosgenin did not significantly alter ATP citrate
      lyase and pyruvate kinase activities but significantly increased glucose-6
      phosphate dehydrogenase activity in the liver compared to diabetic rats. This
      study shows that the feeding of the two test diets to diabetic rats results in
      alterations in the metabolism of glucose with subsequent reduction in plasma
      glucose concentration.

PMID- 15999878
TI  - The effect of phytic acid on the levels of blood glucose and some enzymes of
      carbohydrate and lipid metabolism.
AB  - In this study, six groups of rats were fed as follows: Groups 1 and 2 were fed
      formulated diets supplemented with zinc or without zinc respectively. Groups 3
      and 4 were fed formulated diets supplemented with zinc plus phytic acid extracted
      from sweet potato (Ipomea batatas) or commercial phytic acid respectively. Groups
      5 and 6 were fed formulated diets supplemented with phytic acid extract from
      sweet potato or commercial phytic acid respectively. The animals were fed for
      three weeks and then sacrificed The activities of key enzymes of carbohydrate and
      lipid metabolism as well as transaminases in the liver were determined. Blood
      glucose level was also assessed. Phytic acid extract consumption from sweet
      potato and commercial phytic acid plus zinc supplement lowered blood glucose
      levels. There was no significant change in the activity of 6-phosphogluconate
      dehydrogenase among the groups. Similarly, phytic acid supplementation showed no
      significant decrease in the activity of pyruvate kinase compared to the group fed
      formulated diets. There was a significant increase in the activity of glucose-6
      phosphate dehydrogenase in the groups fed phytic extract from sweet potato
      compared to the other groups. The activities of malic enzyme and ATP-citrate
      lyase in this study were not significantly altered among the groups. There is a
      lowering of blood glucose levels which is desirable for diabetics who consume
      sweet potato diets. The changes in some of the hepatic metabolic enzymes are
      geared towards compensating for the decreased glycolytic responses.

PMID- 15999879
TI  - In vitro activity of sodium-benzoate against isolates of methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND: Worldwide, methicillin-resistant Staphylococcus aureus (MRSA) rates
      have increased dramatically during the last decades. Sodium benzoate (SB) is a
      chemical substance that is used for preparing food and drinks and in the
      treatment of some metabolic (urea cycle disorders and hepatic coma) diseases. No
      studies were found which focussed on the effects of SB in MRSA infections. The
      aim was to determine in vitro activity of sodium benzoate against MRSA clinical
      isolates. METHODS: In this study, MIC for SB in 36 MRSA and 29 methicillin
      sensitive Staphylococcus aureus (MSSA) isolates were determined by a broth
      microdilution method recommended by the National Committee for Clinical
      Laboratory Standards. RESULTS: The MIC at which all of the MRSA and MSSA strains
      were inhibited was at 32 microg/ml and higher concentrations. CONCLUSION: Sodium
      benzoate showed good in vitro activity against clinically relevant MRSA and MSSA
      isolates. It is suggested in this study that this cheap substance, which has been
      used for systemic and local treatment of infection in humans, may be used
      alternatively for the treatment of MRSA infections. However, it is clear that
      more comprehensive and in vivo studies are needed to further elucidate the
      activity of SB against MRSA infections.

PMID- 15999880
TI  - An economic evaluation of laparoscopic cholecystectomy for public hospitals in
      Trinidad and Tobago.
AB  - Laparoscopic Cholecystectomy (LC) is compared to the Open and Minilap approaches
      in a Cost Minimization Analysis for public hospitals in Trinidad and Tobago. The
      analysis shows that despite the high initial equipment cost required to perform
      LC, substantial savings can be achieved at the hospital level by converting from
      a minilap or open regime to a laparoscopic regime for cholecystectomy. Because of
      the reduced recovery period for the patient, LC represents further savings to
      other sectors of the economy as patients return to work much earlier after LC
      than after the other two approaches.

PMID- 15999881
TI  - Estimating the cost of hospital services in a small island state: a case study of
      the Milton Cato Memorial Hospital in St Vincent and the Grenadines.
AB  - Cost estimates are derived for services provided at the Milton Cato Memorial
      Hospital (previously known as the Kingstown General Hospital) using the step-down
      accounting method Both total and average unit cost estimates are provided Among
      the findings of note is that the cost per patient per day spent on the Maternity
      Ward is 57.4% higher than for the Surgical Ward. Even with the 1995 increase in
      user fees, the levels of subsidization for inpatient services remains relatively
      high at 78%-96% for public patients and 43%-72% for private patients. Ancillary
      services werefoundto have lower levels of subsidization and in most cases the
      full costs were recovered from private patients. Laboratory services are not
      subsidized.

PMID- 15999882
TI  - How well does fetal ultrasound predict the date of birth in Antigua and Barbuda?
AB  - This study was done to determine the accuracy of fetal ultrasound (U.S.)
      predicting the estimated date of delivery (EDD) in a primarily Afro-Caribbean
      population in Antigua and Barbuda. A total of 206 women had retrospective review
      offetal ultrasound tests done between July 1994 and January 1996. The EDD based
      on last menstrual period (LMP) was calculated for 104 women with dates and
      compared with EDD calculated from ultrasound test. These were then compared with
      actual date of birth from maternity records. For women with unreliable menstrual
      data (102 women), ultrasound EDD was compared with actual date of birth.
      Ultrasound EDD demonstrated a trend toward being more accurate than menstrual
      history EDD, being 10.0 +/- 9.4 (mean +/- standard deviation) days off versus
      13.3 +/- 15 days, p = 0.057, (n=104), CI: -0.1, 6.73 days. Ultrasound EDD was
      within ten days of delivery 60% of the time versus 57% for menstrual history EDD.
      The average error in estimating EDD was + 1.7 days for ultrasound and + 3.7 days
      for menstrual history. In women without menstrual history data (n=102), the
      ultrasound EDD was just as accurate in both the second trimester, 11.8 +/- 9.5
      versus 11.4 +/- 10.7 days off (not statistically significant) and the third
      trimester, 10.0 +/- 8.0 versus 8.1 +/- 7.0 days off (not statistically
      significant). Fetal ultrasound is marginally better at predicting the date of
      birth compared with menstrual history but the difference does notjustify routine
      use for that purpose. When menstrual history is unknown, ultrasound EDD is just
      as accurate as when menstrual history is known, making it a very useful test.

PMID- 15999883
TI  - The oral contraceptive pill effectively permits cycle batching for an
      intermittent in vitro fertilization programme in Trinidad and Tobago.
AB  - Assisted reproductive technology (ART) in small island states like Trinidad and
      Tobago is usually provided in batches so as to minimize the cost of providing the
      service. As a result, patients 'cycles have to be synchronized in order to
      coincide with the arrival of a visiting embryologist. This is a retrospective
      study which evaluates the experience of pre-treatment with an oral contraceptive
      pill (OCP) as a means of batching cycles for an intermittent ART programme.
      Seventy-four in vitro fertilization (IVF) and intracytoplasmic sperm injection
      (ICSI) cycles in which OCP usage was employed (Group A), were compared with 121
      cycles which did not require pharmaceutical manipulation (Group B). In both
      groups more than 50% of women were older than 36-years. Two cycles were cancelled
      in Group A and seven in Group B, because of poor ovarian response. Although the
      pregnancy rate per treatment cycle was higher in Group A than in Group B (26.3%
      vs 17.3%), this difference was not significant. More spontaneous miscarriages
      occurred in the non-OCP women and ovarian cyst formation was more common in these
      women. The authors experience indicates that the OCP is a simple, cheap and
      efficient means of batching patients for an intermittent ART programme and can be
      utilized in other small ART centres.

PMID- 15999884
TI  - Evaluation of a hypertension screening programme in Independence, Belize.
AB  - This study assesses the effectiveness of a hypertension-screening programme in
      Independence, Belize. Forty-nine of the 101 patients screened were found to have
      elevated blood pressure readings and were advised to seek medical care. Four
      months later, interviews with 35 of the 49 patients from the hypertensive group
      revealed that 85.7% of the patients had sought medical care. Women, elderly
      patients and patients with a previous history of hypertension were more likely
      than men, younger patients and those without a history of hypertension to seek
      follow-up medical care. The screening programme successfully directed a high
      proportion of patients with elevated blood pressure to seek appropriate medical
      care.

PMID- 15999885
TI  - Which anaesthesia should be recommended for prostate biopsy?
AB  - OBJECTIVE: Although transrectal ultrasound-guided prostatic biopsies are
      associated with significant discomfort and pain, most urologists do not use any
      kind of anaesthesia. We therefore compared the efficacy of two local
      anaesthetics, namely, the rectal administration of lidocaine gel and lidocaine
      periprostatic infiltration prior to biopsies. DESIGN AND METHODS: Three hundred
      and fifty-six randomized patients received either 15 mL of 2% lidocaine gel
      administered intrarectally ten minutes before prostate biopsies in group 1 (180
      patients) or 10 mL of 1% lidocaine given under ultrasound guidance in two
      periprostatic injections of 5 mL, four minutes before the biopsies in group 2
      (176 patients). A visual analogue scale (VAS) was used to assess the pain score
      during anaesthesia (VAS 1), during the biopsies (VAS 2) and 30 minutes after them
      (VAS 3). RESULTS: Patients receiving lidocaine gel experienced statistically less
      pain than the lidocaine injection group for mean VAS 1 (0.1 vs 1.4, p < 0.0001)
      and mean VAS 3 (0.8 vs 1.4, p < 0. 001) but VAS 2 showed no statistically
      significant difference (2.0 vs 2.1). No major morbidity was noted with either
      anaesthetic. CONCLUSION: Rectal administration of lidocaine gel is both safe,
      simple and effective and results are more satisfactory than with lidocaine
      periprostatic infiltration.

PMID- 15999886
TI  - A comparison of the objective structured clinical examination results across
      campuses of the University of the West Indies (2001 and 2002).
AB  - OBJECTIVE: To compare the performance of medical students in the Objective
      Structured Clinical Examination (OSCE) of thefinal MBBS Examination across the
      four campuses of The University of the West Indies, over a two-year period DESIGN
      AND METHODS: All final examination results of the Medicine and Therapeutics OSCE
      were collectedfrom the Faculty of Medical Science at the four campuses of The
      University of the West Indies and analyzed using both parametric (t-tests and
      ANOVAs) and non-parametric tests (chi-squared tests). RESULTS: Results indicated
      that students achieved significantly higher mean scores in the 2002 examination
      than in 2001 (t = 3.85, df = 415, p = 0.000). There were no significant
      differences between campuses with regards to the mean corrected score in 2001.
      Also in 2001, in adult stations, all campuses achieved significantly higher
      scores than Jamaica. However, in Jamaica, mean child health station scores were
      significantly higher than all other campuses and, the mean score in Trinidad and
      Tobago was higher than the Bahamas and Barbados. In 2002, all other campuses
      achieved significantly higher scores than Trinidad and Tobago and females
      performed significantly better than males with regards to overall mean scores (t
      = 2.814, df = 189, p = 0.005). Also in 2002, Barbados achieved significantly
      higher mean corrected scores than Trinidad and Tobago (F = 4.649, df = 3191; p =
      0.004) and Barbados and Trinidad and Tobago both obtained significantly higher
      mean child health station scores than Jamaica. CONCLUSIONS: The important
      conclusion from this study is that the OSCE scores in Medicine and Therapeutics
      are generally uniform across the four campuses of the University, thereby
      confirming the consistency of the approach to teaching and helping to validate
      the efficacy and veracity of the medical graduate being produced by The
      University of the West Indies.

PMID- 15999887
TI  - Student self-assessment in a paediatric objective structured clinical
      examination.
AB  - OBJECTIVE: The objective structured clinical examination (OSCE) has been
      recognized not only as a useful assessment tool but also as a valuable method of
      promoting student learning. Student self-assessment is also seen as a means of
      helping students recognize their strengths and weaknesses, understand the
      relevance of core learning objectives and to take more responsibility for each
      stage of their work The authors sought to evaluate the accuracy of medical
      student self-assessment of their performance in the paediatric clerkship OSCE and
      thus obtain preliminary data for use in programme strengthening. DESIGN AND
      METHODS: A self-administered questionnaire was completed by successive groups of
      students immediately after the OSCE at the end of each clerkship rotation.
      Students assessed their performance at each station, using a performance rating
      scale. Performance data were summarized using descriptive and non-parametric
      tests. Basic statistical analysis of the Likert items was conducted by
      calculatingfrequencies, means and standard deviations. Regression analysis was
      used to correlate self-reported rating and actual performance in each station. A
      p value of < 0.05 was considered significant. Eighty-one students (92%) completed
      the questionnaire. RESULTS: Fifty-eight (72%) of the students achieved greater
      than minimum competence in their overall scores. Significant positive correlation
      (p < 0.05) between student self-rating and actual score was noted- among the
      following stations: technical skills, cardiovascular examination, assessment of
      dysmorphism, dermatology, communication and photographic interpretation stations.
      Students overestimated their performance in the gastrointestinal examination,
      radiological and arterial blood gas interpretation. Students underestimated their
      performance in the following: respiratory system, examination of the head,
      developmental and nutritional assessment. CONCLUSIONS: The findings highlight the
      perceived strengths and weaknesses in clinical competence and self-assessment
      skills and provide direction for programme training needs.

PMID- 15999888
TI  - HIV mania as a marker for clinical deterioration in AIDS.
AB  - HIV infection continues to be a significant health problem in the Caribbean
      region. With the availability of antiretroviral drug treatment, it is becoming
      increasingly important to identify clinical markers for deterioration from
      infection to disease. Psychiatric symptoms are well recognized as a complication
      of HIV infection. Three cases are presented to suggest that the occurrence of HIV
      related mania may herald the transition from HIV infection to AIDS. This is
      relevant in assessing the course of the disorder and could indicate that the
      psychiatric manifestation of neurotropic infection represents a distinguishing
      marker for the diagnosis of AIDS perhaps before other clinical signs are evident.

PMID- 15999889
TI  - "Minimal intervention management" for gastroschisis: a preliminary report.
AB  - The replacement of eviscerated bowel, without anaesthesia, has been performed
      safely in stable neonates with gastroschisis. This technique, termed "minimal
      intervention management", was used in three infants treated at the Newborn
      Special Care Nursery of the University Hospital of the West Indies. Two infants
      had excellent results but one had bowel perforation during the procedure,
      necessitating conversion to formal laparotomy under general anaesthesia. In
      selected patients, advantages of this technique include the ability to be guided
      by patient response during the procedure in order to avoid excessive intra
      abdominal tension, the avoidance of anaesthesia and minimal cost. This technique
      is proposed for wider use in developing countries.

PMID- 15999890
TI  - Sir William Osler founder of Anglo-American Scientific Clinical Medicine and its
      teaching.

PMID- 15999891
TI  - A citation to Kenrick Orrin Evan Barrow.

PMID- 15999892
TI  - Trauma, the forgotten disease.

PMID- 15999893
TI  - Clinical applications of computed tomography angiography in neuroimaging.
AB  - Recent technical advances in multidetector computed tomography angiography (CTA)
      now allow for the noninvasive evaluation of the neurovascular tree. In the
      evaluation of intracranial aneurysms, stroke imaging, and other vascular
      abnormalities, CTA compares favorably with conventional angiography. Several
      illustrative case reports are presented and the advantages of CTA over
      conventional angiography are discussed.

PMID- 15999894
TI  - Insulating patients from the cost of health care: changes in the financing and
      regulation of health care in the past 50 years.
AB  - The evolution of the current financing of health care in the United States has
      been outlined. Although the decisions leading to the current system have been
      well intentioned, the result is a costly system in which many patients are left
      without health insurance coverage. Two methods of reconnecting patients to the
      cost of care are presented (tiered co-pays and MSAs), which may be acceptable to
      patients. We can only hope that, over time, these types of cost-sharing methods,
      combined with the evolution of other patient-centric, "evidence-based" models of
      care (such as identification and intensive case management of high-risk cases)
      may lead to a more efficient and affordable system of health care in the United
      States.

PMID- 15999895
TI  - Ethics committee deliberates stem cell research.

PMID- 15999896
TI  - Embryonic stem cells--questions.

PMID- 15999897
TI  - Why embryonic stem cell research should be banned forever.

PMID- 15999898
TI  - Tsunami relief program update.

PMID- 15999899
TI  - EEG databases in research and clinical practice: current status and future
      directions.

PMID- 15999900
TI  - Discovery and integrative neuroscience.
AB  - Hypothesis driven research has been shown to be an excellent model for pursuing
      investigations in neuroscience. The Human Genome Project demonstrated the added
      value of discovery research, especially in areas where large amounts of data are
      produced. Neuroscience has become a data rich field, and one that would be
      enhanced by incorporating the discovery approach. Databases, as well as
      analytical, modeling and simulation tools, will have to be developed, and they
      will need to be interoperable and federated. This paper presents an overview of
      the development of the field of neuroscience databases and associate tools:
      Neuroinformatics. The primary focus is on the impact of NIH funding of this
      process. The important issues of data sharing, as viewed from the perspective of
      the scientist and private and public funding organizations, are discussed.
      Neuroinformatics will provide more than just a sophisticated array of information
      technologies to help scientists understand and integrate nervous system data. It
      will make available powerful models of neural functions and facilitate discovery,
      hypothesis formulation and electronic collaboration.

PMID- 15999901
TI  - Integrative neuroscience: the role of a standardized database.
AB  - Most brain related databases bring together specialized information, with a
      growing number that include neuroimaging measures. This article outlines the
      potential use and insights from the first entirely standardized and centralized
      database, which integrates information from neuroimaging measures (EEG, event
      related potential (ERP), structural/functional MRI), arousal (skin conductance
      responses (SCR)s, heart rate, respiration), neuropsychological and personality
      tests, genomics and demographics: The Brain Resource International Database. It
      comprises data from over 2000 "normative" subjects and a growing number of
      patients with neurological and psychiatric illnesses, acquired from over 50
      laboratories (in the U.S.A, United Kingdom, Holland, South Africa, Israel and
      Australia), all with identical equipment and experimental procedures. Three
      primary goals of this database are to quantify individual differences in
      normative brain function, to compare an individual's performance to their
      database peers, and to provide a robust normative framework for clinical
      assessment and treatment prediction. We present three example demonstrations in
      relation to these goals. First, we show how consistent age differences may be
      quantified when large subject numbers are available, using EEG and ERP data from
      nearly 2000 stringently screened. normative subjects. Second, the use of a
      normalization technique provides a means to compare clinical subjects (50 ADHD
      subjects in this study) to the normative database with the effects of age and
      gender taken into account. Third, we show how a profile of EEG/ERP and autonomic
      measures potentially provides a means to predict treatment response in ADHD
      subjects. The example data consists of EEG under eyes open and eyes closed and
      ERP data for auditory oddball, working memory and Go-NoGo paradigms. Autonomic
      measures of skin conductance (tonic skin conductance level, SCL, and phasic skin
      conductance responses, SCRs) were acquired simultaneously with central EEG/ERP
      measures. The findings show that the power of large samples, tested using
      standardized protocols, allows for the quantification of individual differences
      that can subsequently be used to control such variation and to enhance the
      sensitivity and specificity of comparisons between normative and clinical groups.
      In terms of broader significance, the combination of size and multidimensional
      measures tapping the brain's core cognitive competencies, may provide a normative
      and evidence-based framework for individually-based assessments in "Personalized
      Medicine."

PMID- 15999902
TI  - The Australian EEG database.
AB  - The Australian EEG Database is a web-based de-identified searchable database of
      18,500 EEG records recorded at a regional public hospital over an 11-year period.
      Patients range in age from a premature infant born at 24 weeks gestation, through
      to people aged over 90 years. This paper will describe the history of the
      database, the range of patients represented in the database, and the nature of
      the text-based and digital data contained in the database. Preliminary results of
      the first two studies undertaken using the database are presented. Plans for
      sharing data from the Australian EEG database with researchers are discussed. We
      anticipate that such data will be useful in not only helping to answer clinical
      questions but also in the field of mathematical modeling of the EEG.

PMID- 15999903
TI  - Use of normative databases and statistical methods in demonstrating clinical
      utility of QEEG: importance and cautions.
AB  - The clinical utility of the EEG, especially in psychiatric, learning and
      cognitive disorders, has been greatly enhanced by the use of quantitative
      analysis (QEEG) and comparisons to a normative database. Of primary importance in
      the use of such a reference database are the following considerations and
      cautions: adequate sampling across a broad age range; consideration of
      inclusion/exclusion criteria; adequate sample of artifact-free data to
      demonstrate reliability and replicability of norms; demonstration of specificity
      and sensitivity. A normative database meeting these criteria allows the
      multivariate description of patterns of QEEG abnormalities in patients as
      compared to age appropriate normative values, and the exploration of
      neurophysiological heterogeneity within populations. Demonstrations of the
      clinical significance of this approach exist in the scientific literature and
      demonstrate that QEEG provides high sensitivity and specificity to abnormalities
      in brain function seen in psychiatric populations.

PMID- 15999904
TI  - Long latency evoked potential database for clinical applications: justification
      and examples.
AB  - We summarize our experience with the clinical utility of long latency evoked
      potential (EP) data in clinical QEEG studies. In contrast to common wisdom, such
      EP data are consistent across appropriately chosen age groups. In a healthy adult
      population, EP data correlate consistently with independently collected
      psychological variables. In our pediatric referral population, EP data are of
      greatest and most unique value in the learning disabilities but also augment
      detection of abnormality in epilepsy and behavioral abnormality. Selection of
      subjects for a clinical database on the basis of examined medical, neurological
      and behavioral health, forms adequately consistent groupings for clinical
      utility. The use of the Z-SPM is essential for detection of EP abnormality. A
      minimum of three replications within a clinical study protects against
      chance/false positives. Also, the true data dimensionality within EP data sets is
      far less than the total number of variables typically collected.

PMID- 15999905
TI  - Clinical database development: characterization of EEG phenotypes.
AB  - We propose development of evidence-based methods to guide clinical intervention
      in neurobehavioral syndromes based on categorization of individuals using both
      behavioral measures and quantification of the EEG (qEEG). Review of a large
      number of clinical EEG and qEEG studies suggests that it is plausible to identify
      a limited set of individual profiles that characterize the majority of the
      population. Statistical analysis has already been used to document "clusters" of
      qEEG features seen in populations of psychiatric patients. These clusters are
      considered here as intermediate phenotypes, based on genetics, and are reliable
      indices of brain function, not isomorphic with DSM categories, and carry
      implications for therapeutic intervention. We call for statistical analysis
      methods to be applied to a broad clinical database of individuals diagnosed with
      neurobehavioral disorders in order to empirically define clusters of individuals
      who may be responsive to specific neurophysiologically based treatment
      interventions, namely administration of psychoactive medication and/or EEG
      neurofeedback. A tentative set of qEEG profiles is proposed based on clinical
      observation and experience. Implication for intervention with medication and
      neurofeedback for individuals with these neurophysiological profiles and specific
      qEEG patterns is presented.

PMID- 15999906
TI  - EEG mapping and low-resolution brain electromagnetic tomography (LORETA) in
      diagnosis and therapy of psychiatric disorders: evidence for a key-lock
      principle.
AB  - Different psychiatric disorders, such as schizophrenia with predominantly
      positive and negative symptomatology, major depression, generalized anxiety
      disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia,
      senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that
      differ statistically both from each other and from normal controls.
      Representative drugs of the main psychopharmacological classes, such as sedative
      and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics,
      psychostimulants and cognition-enhancing drugs, induce significant and typical
      changes to normal human brain function, which in many variables are opposite to
      the above-mentioned differences between psychiatric patients and normal controls.
      Thus, by considering these differences between psychotropic drugs and placebo in
      normal subjects, as well as between mental disorder patients and normal controls,
      it may be possible to choose the optimum drug for a specific patient according to
      a key-lock principle, since the drug should normalize the deviant brain function.
      This is supported by 3-dimensional low-resolution brain electromagnetic
      tomography (LORETA), which identifies regions within the brain that are affected
      by psychiatric disorders and psychopharmacological substances.

PMID- 15999907
TI  - Evaluation and validity of a LORETA normative EEG database.
AB  - To evaluate the reliability and validity of a Z-score normative EEG database for
      Low Resolution Electromagnetic Tomography (LORETA), EEG digital samples (2 second
      intervals sampled 128 Hz, 1 to 2 minutes eyes closed) were acquired from 106
      normal subjects, and the cross-spectrum was computed and multiplied by the Key
      Institute's LORETA 2,394 gray matter pixel T Matrix. After a log10 transform or a
      Box-Cox transform the mean and standard deviation of the *.lor files were
      computed for each of the 2394 gray matter pixels, from 1 to 30 Hz, for each of
      the subjects. Tests of Gaussianity were computed in order to best approximate a
      normal distribution for each frequency and gray matter pixel. The relative
      sensitivity of a Z-score database was computed by measuring the approximation to
      a Gaussian distribution. The validity of the LORETA normative database was
      evaluated by the degree to which confirmed brain pathologies were localized using
      the LORETA normative database. Log10 and Box-Cox transforms approximated Gaussian
      distribution in the range of 95.64% to 99.75% accuracy. The percentage of
      normative Z-score values at 2 standard deviations ranged from 1.21% to 3.54%, and
      the percentage of Z-scores at 3 standard deviations ranged from 0% to 0.83%. Left
      temporal lobe epilepsy, right sensory motor hematoma and a right hemisphere
      stroke exhibited maximum Z-score deviations in the same locations as the
      pathologies. We conclude: (1) Adequate approximation to a Gaussian distribution
      can be achieved using LORETA by using a log10 transform or a Box-Cox transform
      and parametric statistics, (2) a Z-Score normative database is valid with
      adequate sensitivity when using LORETA, and (3) the Z-score LORETA normative
      database also consistently localized known pathologies to the expected Brodmann
      areas as an hypothesis test based on the surface EEG before computing LORETA.

PMID- 15999908
TI  - Efficient application of Internet databases for new signal processing methods.
AB  - This paper highlights the ways in which Internet databases may be efficiently
      used to foster the application of progress in biomedical sciences via data
      sharing and new algorithms. Employing the Internet to accelerate the pace of
      interdisciplinary research has significant potential, yet as with all new
      technologies, the first applications often cause more disappointment than
      positive outcomes. We discuss examples of solutions to the basic issues: (1)
      finding the relevant datasets (in portals connected via the Inter-neuro
      infrastructure), (2) reading the particular format in which the data was stored
      (using the SignalML language for metadescription of time series), (3) choosing
      the right method for the data analysis (we provide a brief review of the methods
      used for the analysis of EEGs, and discuss two of them in detail: Directed
      Transfer Function and Matching Pursuit), and (4) sharing the software for chosen
      methods of analysis (via repositories such as the eeg.pl thematic portal).

PMID- 15999909
TI  - Combined antibiogram for hospitals with 50+ beds--Alaska, 2002.
AB  - Hospital antibiograms are compiled from facility microbiology laboratories and
      list specific organism-antimicrobial susceptibility combinations. Antibiograms
      can then be used by facility health care providers to guide choices of
      antimicrobials for treatment. For a specific time period, antibiograms from
      different facilities can be aggregated. These summaries are quick and easy to
      compile and can provide an overview of antimicrobial susceptibility in a region.
      We aggregated year 2002 antibiograms from nine Alaska hospitals with 50 or more
      beds. Data presented here suggest that a combined antibiogram can provide a rough
      summary of susceptibility estimates statewide, and demonstrate trends in
      decreasing susceptibility, as seen for methicillin-resistant Staphylococcus
      aureus. For future antibiogram summaries, other organisms can be added as they
      gain in relevance or concern, or other antimicrobials added as usage or
      resistance patterns change.

PMID- 15999910
TI  - Over-representation of Samoan/Pacific Islanders among patients with methicillin
      resistant Staphylococcus aureus (MRSA) infections at a large family practice
      clinic in Anchorage, Alaska, 1996-2000.
AB  - Two pediatricians in Anchorage observed that among patients of Samoan/Pacific
      Islander (S/PI) descent, bacterial wound cultures that grew Staphylococcus aureus
      often yielded methicillin-resistant isolates. The Alaska Section of Epidemiology
      performed chart reviews of patients that visited a large family practice clinic
      in Anchorage, Alaska, from 1996 through April 2000, and who were diagnosed with a
      skin infection. Eight of 204 patients were identified with culture-confirmed MRSA
      infections. Eighty percent (4 of 5) of S/PI patients had resistant isolates
      compared with 12% (4 of 34) of non S/PI patients (Yates corrected chi2 = 8.61, p
      value = 0.003). Although subject to limitations, these data support similar
      findings documented by other studies that suggest MRSA infections
      disproportionately affect persons of S/PI origin. This study also suggests that
      it would be prudent to reduce the threshold of clinical suspicion for obtaining a
      skin culture among S/PI patients in Alaska, and avoid beta-lactam antibiotics
      until culture results are received.

PMID- 15999911
TI  - Platelet count assessment from peripheral blood smear (PBS).
AB  - OBJECTIVE: To visually count platelets in a peripheral blood smear and compare
      with an automated machine platelet count. METHODS: Thirty-five peripheral blood
      smears were made from blood specimens counted on an automated blood cell machine:
      twenty-three thrombocytopenic specimens, 1 with high platelet count and 11 with
      normal counts. Ten and 25 high-power fields were microscopically averaged and
      then multiplied by 15,000 and 20,000 to arrive at a platelet count in 1,000 per
      microliter. Comparisons between visual and machine counts were drawn. RESULTS:
      There was fair concordance in 27 specimens. In three specimens underestimation
      was found, overestimation in five. A 15,000 multiplier gave slightly better
      results than 20,000. Average in 10 high-power fields was as good as 25. Abnormal
      counts could be assessed as well as normal. CONCLUSION: Average in 10 high-power
      field on a blood film microscopically and multiplying by 15,000 gives a platelet
      count reasonably close to automated machine counts in thousands per microliter.

PMID- 15999912
TI  - Barriers or facilitators?

PMID- 15999913
TI  - Enhancing communication between hospital and community: multidisciplinary
      discharge case conferences.

PMID- 15999914
TI  - Applying health technology assessment to pharmaceutical care: pitfalls and future
      directions.
AB  - It has been argued in previous issues of this journal that health technology
      assessment can be used as a tool to assess the eciency of pharmaceutical care by
      linking its impact on clinical and humanistic outcomes to the resources required
      to achieve these outcomes. Additionally, as policy-makers appreciate the need to
      evaluate projects on the basis of their costs and benefits, the application of
      health technology assessment to pharmaceutical care may serve as a way of
      communicating with policy-makers and informing policy on pharmaceutical care.
      This article elaborates on this idea by arguing that policy-makers will be more
      likely to appreciate the value of pharmaceutical care if researchers pay more
      attention to some methodological principles underlying health technology
      assessment in the context of pharmaceutical care, and if they take into account
      the decision-making context facing policy-makers. In order to raise the
      methodological quality of studies, researchers need to take care to define better
      the pharmaceutical care intervention; to evaluate the costs of the intervention
      and its impact on the utilization of other health services; and to aggregate the
      various clinical and humanistic outcome measures that are commonly used in this
      type of research. In order to increase the usefulness of study findings to policy
      makers, researchers need to identify the multiple objectives that policy-makers
      pursue, and show how study findings will aid policy-makers in attaining these
      objectives.

PMID- 15999915
TI  - Rational use of medicines--an important issue in pharmaceutical policy.
AB  - In this article the authors deal with issues of drug utilisation from a clinical
      and policy perspective. They address the difficulties of managing drug therapy on
      a population level, which is known among professionals, as the problem of
      rational use of medicines. Various definitions and interpretations are presented
      and compared. This is followed by a presentation of the concerns associated with
      pharmaceutical marketing from a policy perspective, including the fear that the
      dominance of information produced by industry may lead to irrational drug use.
      Next, the authors review the tools for policy making including educational,
      managerial, and regulatory interventions. The (often overlapping) concepts of
      medicines management, clinical pharmacy and pharmaceutical care are then
      discussed to show how professionals, sometimes in collaboration with
      policymakers, have tackled the problem of nonrational use of medicines. The
      authors address the question as to whether the rational use of medicines a
      universal concept, whether it can be and whether it should be? They argue that,
      as with most concepts, the rational use of medicines must always be viewed in
      context. They conclude that pharmacy needs to adapt its way of thinking to
      include the issue of context. They point out that clinical pharmacists today
      already adapt their decisons to each patient and patient group. Policy-makers are
      encouraged to adopt a similar approach because populations as well as particular
      market situations vary and therefore policy solutions cannot be considered
      universal.

PMID- 15999916
TI  - Treatment failures secondary to drug interactions with divalent cations and
      fluoroquinolone.
AB  - We observed four cases of therapeutic failures while patients were simultaneously
      taking medications that contained divalent cations and oral fluoroquinolones.
      Patients improved after conversion to the intravenous formulation of the same
      antibiotics, proper spacing of the divalent cation, or conversion to a different
      antibiotic class. Patients prescribed oral fluoroquinolones should receive
      instructions on proper separations of these antibiotics with divalent cations.
      Health care professionals should be cognizant of these interactions and educated
      on their potential deleterious effect.

PMID- 15999917
TI  - Choice of GPIIb/IIIa antagonist in percutaneous coronary intervention: how should
      economic criteria be factored in?
AB  - OBJECTIVE: Three GPIIb/IIIa antagonists are available in the market. In France,
      as in many countries, their acquisition costs strongly differ. The objective of
      this study was to analyze how economic criteria-beyond the acquisition cost
      should be factored in, when choosing a GPIIb/IIIa antagonist. METHOD: Both
      clinical and economic papers on the use of GPIIb/IIIa antagonists in percutaneous
      coronary interventions published in peer-review journals from 1994 to 2002 were
      reviewed and analyzed. RESULTS: Cost differentials between products strongly vary
      from one 'cost concept' to another, i.e., acquisition cost, administration cost,
      hospital cost, net treatment cost. The comparison of efficacy is even more
      complicated, as most of the time only indirect comparisons are available, based
      on different clinical studies, with different durations and definitions of
      outcomes. Finally, cost-effectiveness ratios range from US dollar 10,695 per
      avoided event for eptifibatide (IMPACT II study) to US dollar 74,047 for
      tirofiban (RESTORE study). CONCLUSION: The concept of cost, inevitably entering
      into the choice of a medicinal strategy, must be used with caution. The amplitude
      of the difference between products, and the product favored by the difference,
      vary according to the cost concept retained.

PMID- 15999918
TI  - Boron neutron capture therapy for glioblastoma multiforme.
AB  - AIM: Glioblastoma multiforme (GBM) is an incurable disease that can only be
      managed in a palliative way. The GBM accounts for approximately half of all newly
      diagnosed primary brain tumors with an incidence of 2-3 cases per 100,000 people
      each year. Surgery and radiation are the standard options for palliation, and
      whether there is a place for chemotherapy is still discussed. Boron neutron
      capture therapy (BNCT) is a promising and possibly curative method of treating
      GBM. The purpose of this article is to provide an updated review on the current
      management and future possibilities of treating GBM with BNCT. METHOD: Use was
      made of computerized searches and of checking cross-references of articles and
      book chapters. RESULTS: The principle of BNCT uses the high ability of 10B to
      capture thermal neutrons and to disintegrate immediately into a He nucleus (alpha
      particle) and a Li nucleus. To reach a sufficient concentration of 10B in the
      malignant cells compared to the surrounding healthy tissue, 10B-carriers must be
      highly tumor-selective. At present, the 10B carriers boronophenylalanine (BPA)
      and sodium borocaptate (BSH) are used in clinical trials to perform BNCT.
      CONCLUSION: The BNCT is a promising and possibly curative method of treating GBM,
      but at present this procedure is far from perfect. Because of the lack of
      selectivity of the boron carriers, it appears so far that radiation toxicity
      limits the radiation dose, so that tumor damage is modest. Current investigations
      and developments are aimed at targeting the boron carriers to the tumor, in order
      to limit the damage to the healthy, surrounding tissue.

PMID- 15999919
TI  - Psychometric assessment and application of a questionnaire measuring patient:
      satisfaction with information on cancer treatment.
AB  - OBJECTIVE: Pharmaceutical care follows a needs-based approach. Cancer patients
      form a group with particular needs. Information about cancer treatment plays an
      important role in terms of coping strategies, initiation of self-care behaviour,
      and quality of life. In order to develop pharmaceutical care strategies for
      cancer patients, it is important to assess patients' information needs. This
      survey aims at providing a suitable instrument to measure patient satisfaction
      with information on cancer treatment and to reveal the present situation in
      Germany. METHODS: Since there was no suitable German measure available, the
      Canadian 'Patient Satisfaction with Cancer Treatment Education (PS-CaTE)
      questionnaire' was translated into German and its test quality criteria were
      examined. Selected socio-demographic variables were added to the original version
      of the questionnaire to facilitate subgroup analysis. A pre-test was performed to
      assess the reliability of the adapted instrument. The questionnaire was
      distributed among patients of cooperating hospitals, oncology practices, and self
      aid groups over Germany. RESULTS: The pre-test established a good reliability of
      the instrument. In the main survey, overall satisfaction, on a 5-point Likert
      scale, showed a median score of 3.5, where 5 represented the highest degree of
      satisfaction. A subscale analysis revealed that satisfaction with information
      provided on adverse events and complementary treatment options was lower compared
      to the information provided on cancer treatment. A stepwise multiple-regression
      analysis identified three significant predictors of satisfaction: a) diagnosis of
      a mammary carcinoma; b) recent diagnosis; and c) treatment by a primary-care
      oncologist. Patients with a mammary carcinoma and patients treated by a primary
      care oncologist were less satisfied, and patients with a recent diagnosis were
      more satisfied compared to other patients. In comparison to other information
      sources, pharmacists still seem to play a minor role as a source of information
      for patients. CONCLUSIONS: The version of the questionnaire with a total of 14
      items seems to be suitable for measuring patient satisfaction with information.
      Additional research is needed to further verify the validity of the instrument.
      The questionnaire may help pharmaceutical-care providers to develop needs-based
      information strategies. The assessment of patient satisfaction can contribute to
      the outcome evaluation of pharmaceutical care. The fact that pharmacists are not
      yet being recognised by most patients as a source of information should support
      an intensified and more active offer of care by the pharmacist.

PMID- 15999920
TI  - Utilisation of macrolides and the development of Streptococcus pyogenes
      resistance to erythromycin.
AB  - OBJECTIVES: The aim of the study was to evaluate the relationship between the
      development of the resistance of Streptococcus pyogenes strains to erythromycin
      and the utilisation of macrolides in the Olomouc region, Czech Republic. METHOD:
      During the period 1997-2001, data for utilisation of macrolides was obtained from
      the database of the regional General Health Insurance Company and expressed
      indefined daily doses per 1,000 patients per day. S. pyogenes strains were
      isolated from community patients suffering from acute bacterial tonsillitis.
      Their susceptibility to antibiotics was assessed by the disk diffusion method.
      RESULTS: Utilisation of macrolides increased by 13% in the period 1997-2001;
      their utilisation represented 11.40% of total antibiotic prescription in 1997 and
      15.48% in 2001. Occurrence of erythromycin-resistant S. pyogenes strains
      increased significantly from 14% in 1997 to 32% in the year 2001 (P < 0.01). In
      2000, macrolides consumption decreased non-significantly, but with no concomitant
      decrease in erythromycin-resistant S. pyogenes strains occurrence. Absolute
      susceptibility of S. pyogenes, the most important bacterial pathogen in community
      acquired bacterial tonsillitis, to penicillin contrasts with increasing macrolide
      resistance. CONCLUSIONS: The study documents the influence of increased
      utilisation of macrolides on bacterial resistance. Penicillin should be a first
      choice antibiotic in acute bacterial tornsillitis; macrolides should only be
      reserved for patients allergic to penicillins.

PMID- 15999921
TI  - A qualitative study of health-care personnel's experience of a satellite pharmacy
      at a HIV clinic.
AB  - OBJECTIVE: The aim of the study was to investigate how health-care personnel at a
      HIV clinic perceived conventional pharmacies in Sweden and whether the
      decentralization of pharmaceutical services to the HIV clinic had led to an
      improved collaboration between other health-care professionals and pharmacists.
      METHODS: Doctors and nurses who had regular contacts with HIV patients and the
      satellite pharmacy were interviewed. The interviews were semi-structured, using
      open questions and was analysed according to the phenomenographic approach.
      RESULTS: The respondents perceived the existing co-work between conventional
      pharmacies and other health care professionals as limited. The availability of
      the satellite pharmacy enabled the health care professionals to understand the
      pharmacys' way of working, and to increase trust in the pharmacy staff.
      Collaboration was hence developed between the professions, leading to a
      consistent way of informing the patients about their HIV drugs, thereby avoiding
      contradictory information. The pharmacist also became involved in adherence
      promoting activities at the clinic. The perceived benefits for the patients were
      considered to be convenience and preservation of privacy as well as a better
      basis for safe and appropriate drug utilisation. CONCLUSION: Conventional
      pharmacies were shown to have several disadvantages in serving the HIV infected
      population. The health care professionals found the novel approach of dispensing
      HIV drugs at the clinic valuable. The approach led to increased communication and
      trust between the health care professions, and enhanced teamwork in medication
      management.

PMID- 15999922
TI  - Medication errors when transferring elderly patients between primary health care
      and hospital care.
AB  - OBJECTIVE: The aims were to evaluate the frequency and nature of errors in
      medication when patients are transferred between primary and secondary care.
      METHOD: Elderly primary health care patients (> 65 years) living in nursing homes
      or in their own homes with care provided by the community nursing system, had
      been admitted to one of two hospitals in southern Sweden, one university hospital
      and one local hospital. A total of 69 patient-transfers were included. Of these,
      34 patients were admitted to hospital whereas 35 were discharged from hospital.
      MAIN OUTCOME MEASURE: Percentage medication errors of all medications i.e. any
      error in the process of prescribing, dispensing, or administering a drug, and
      whether these had adverse consequences or not. RESULTS: There were 142 medication
      errors out of 758 transfers of medications. The patients in this study used on an
      average more than 10 drugs before, during and after hospital stay. On an average,
      there were two medication errors each time a patient was transferred between
      primary and secondary care. When patients were discharged from the hospital, the
      usage of a specific medication dispensing system constituted a significant risk
      for medication errors. The most common error when patients were transferred to
      the hospital was inadvertent withdrawal of drugs. When patients left the hospital
      the most common error was that drugs were erroneously added. CONCLUSION:
      Medication errors are common when elderly patients are transferred between
      primary and secondary care. Improvement in documentation and transferring data
      about elderly patients' medications could reduce these errors. The specific
      medication dispensing system that has been used in order to increase safety in
      medication dispensing does not seem to be a good instrument to reduce the number
      of errors in transferring data about medication.

PMID- 15999923
TI  - Gabexate mesilate and acute pancreatitis: an experience of evidence based drug
      information for improving rational drug use.
AB  - INTRODUCTION: Gabexate mesylate is a drug marketed only in Italy and Japan and it
      is considered an essential drug in the treatment of acute pancreatitis. A
      periodic revision and evaluation of drug utilization in our hospital demonstrated
      that the dosages and indications of Gabexate mesilate (GM) did not follow those
      settled by the National Health System and by our Hospital Formulary. We therefore
      promoted and conducted a program of drug information and meetings with the
      physicians in order to improve the correct utilisation of GM and identify
      potential problems. METHODS: GM prescriptions in 1999 were analysed for
      indications and dosages. Scheduled meetings with the medical staff were
      successively started in order to debate current therapies and treatments of acute
      pancreatitis using the criteria of evidence-based medicine (EBM). Follow-up was
      done in 2000, 2001 and 2002 to evaluate the efficacy of our intervention.
      RESULTS: The hospital board and 20 physicians were involved in this program of
      evidence-based drug information. The follow-up and the monitoring of GM
      prescriptions showed a reduction in the utilisation of GM in the subsequent
      period. CONCLUSIONS: GM is one of the most expensive drugs in our hospital, but
      its benefits are not very evident. Moreover, the international guidelines and
      literature ascribe to GM only a marginal role in the treatment of acute
      pancreatitis. Evidence-based medicine strengthens clinical experience with the
      evidence from the literature and underlines that essential drugs are used
      worldwide.

PMID- 15999924
TI  - Cardiovascular drug use and differences in the incidence of cardiovascular
      mortality in elderly Serbian men.
AB  - OBJECTIVE: To assess whether the difference in risk of cardiovascular mortality
      between urban and rural areas of Serbia could be explained by differences in the
      use of cardiovascular medication. METHODS: The Serbian cohorts of the Seven
      Countries Study, Velika Krsna (VK), Zrenjanin (ZR) and Belgrade (BG), were
      enrolled in 1962-1964 and were followed up for 25 years. The survivors of these
      cohorts were re-examined in 1987, 1988 and 1989, respectively. This second
      examination of elderly men aged 65 to 84 years included a questionnaire about
      current use of cardiovascular medication, risk factors and diseases and a
      physical examination. All subjects were followed until death or the predefined
      censor date (10 years after baseline). The Cox proportional hazards model was
      used to calculate the risk of cardiovascular mortality in the rural cohorts
      compared to the urban cohort and to adjust for confounding. MAIN OUTCOME MEASURE:
      Cardiovascular death. RESULTS: A total of 227 men from VK, 184 men from ZR and
      287 men from BG were followed for a mean duration of 7.4 years and was complete
      for all subjects. After exclusion of 13 subjects with missing medication data,
      the incidences of cardiovascular mortality in VK, ZR, and BG were 60, 74, and 26
      per 1,000 person-years, respectively. The prevalence of cardiovascular medication
      use was 38% in VK, 52% in ZR, and 59% in BG. The greatest difference in use of
      specific medication was observed for betablockers (0% in VK and ZR, 13% in BG).
      After adjustment for cardiovascular risk factors, diseases and age, the relative
      risks (RRs) of cardiovascular mortality were 2.12 [95% CI: 1.44-3.12], and 2.27
      [95% CI: 1.56-3.30] in VK, and ZR compared to BG. Additional adjustment for the
      use of cardiovascular medication increased these RRs to 2.40 [95% CI: 1.61-3.60]
      and 2.55 [95% CI: 1.72-3.78], respectively. CONCLUSION: The variation in
      cardiovascular medication use could not explain the excess risk of mortality in
      the rural Serbian cohorts compared to urban Belgrade.

PMID- 15999925
TI  - Volume and market share of anti-epileptic drugs in The Netherlands: impact of new
      drugs.
AB  - OBJECTIVE: In the past decade, several new anti-epileptic drugs (AEDs) were
      introduced in The Netherlands. These new drugs, one of which is lamotrigine, are
      6 to 10 times more expensive than conventional anti-convulsants. In 1997, the
      high cost of lamotrigine, together with a lack of clinical data supporting its
      superiority over conventional drugs, prompted the Dutch Health Insurance Board to
      release a guideline in which the use of lamotrigine was restricted to difficult
      to-treat patients. Other new drugs that were marketed after 1997 also became
      subject to this guideline. The utilisation of new AEDs and the cost consequences
      are the subject of this paper. METHODS: Data from extramurally prescribed AEDs
      was obtained from the Dutch Drug Information Project, which is a database
      containing prescriptions for about 5.5 million inhabitants of the Netherlands.
      This data was used to study the impact of new AEDs on volume and market share of
      AEDs in the period from 1995 to 2001 in The Netherlands. RESULTS: Between 1995
      and 2001, the total volume of AEDs increased by 130%, 60% of which consisted of
      new AEDs. Gabapentin, lamotrigine and oxcarbazepine were the most frequently
      prescribed new compounds. The volume share of new AEDs increased from 5% in 1995
      to 18% in 2001. The market share amounted to 21.5 million euros in 1995 and rose
      to 47 million euros in 2001; 80% of this increase was due to the introduction of
      new AEDs. DISCUSSION: Although in 2001 the volume share of new AEDs was still
      modest, their introduction has led to a strong increase in the cost. New data is
      emerging on the effectiveness and cost-benefit sum of the new AEDs; this may
      change the place in therapy of these drugs. Because of their strong potential to
      force up cost, the positioning of new AEDs requires further attention.

PMID- 15999926
TI  - [Dear female reader, dear male reader].

PMID- 15999927
TI  - [Polytrauma on the way. Simple measures for efficient life-saving care!].
AB  - The General Practitioner (GP) doesn't usually treat polytrauma often. However in
      Switzerland there are many remote areas where he is first on the scene of the
      accident. Thus it is important that he knows basic treatment principles in this
      situation such as the ABC according to the ATLS guidelines. We give a short
      overview of these important principles.

PMID- 15999928
TI  - [The comatose patient].
AB  - Consciousness and wakefulness require normal functioning of the cerebral cortex,
      as well as of the midbrain reticular formation and its ascending projections.
      Bilateral structural lesions or functional disturbances of these brain areas can
      impair consciousness and can produce coma. The bodily posture and brainstem
      reflexes of the comatose patient provide clues as to whether the lesion lies in
      the brainstem or in the cerebral hemispheres. Brainstem reflexes are usually
      preserved in coma due to bilateral hemispheric dysfunction, including metabolic,
      anoxic, and toxic coma. Ancillary tests are used to answer specific diagnostic
      questions. The treatment of coma depends on its etiology.

PMID- 15999929
TI  - [Abdominal pain in emergency service--what should I not forget?].
AB  - Abdominal pain for the General Practitioner (GP) is an important problem and
      presents as a significant challenge since the complaint emerges to the primary
      care provider as one of the 3 most important complaints. This paper serves as a
      facilitator and guide in helping the General Practitioner differentiate between
      the so-called normal abdominal pain versus severe abdominal pain which should be
      referred to a specialist. One of the most important messages the paper attempts
      to convey is that patients have to be seen and personally examined by the General
      practitioner. This is a paramount feature in establishing course of severity and
      outcome. Since approximately 25% of all presenting abdominal pain complaints are
      unclear, even to the experienced specialist, the authors attempt to direct a
      focused exam by means of a thorough history and physical examination and then to
      formulate a decision tree regarding the question of referral or continued primary
      care by the provider.

PMID- 15999930
TI  - [Emergency due to allergy: the therapy--adrenaline for physicians and patients].
AB  - Emergency due to allergy may proceed within minutes to life-threatening
      respiratory and circulatory problems. Therefore, after diagnosis prompt and
      correct therapy might be vital. Because of its effect on alpha-, beta1-, and
      beta2-receptors, adrenaline is the treatment of choice in emergency due to
      allergy. For fear of cardiovascular side effects, often adrenaline is withheld
      even in case of anaphylaxis. If given properly such as an intramuscular injection
      the danger of undesirable side effects, however, is small. After a systemic,
      allergic reaction each patient needs to be equipped with rescue medications. If
      an adrenaline-containing device is prescribed--nowadays with EpiPen and the
      metered-dose inhaler Primatene Mist 2 systems are available--, the patient must
      get a correct instruction in its use. In case of a severe allergic reaction,
      antihistamines and corticosteroids are given in second line. Following any
      systemic allergy, an allergological work-up should be required. Only through
      exact diagnosis and profound patient's education, recurrences can be avoided, and
      in some cases, specific immunotherapy is indicated.

PMID- 15999931
TI  - [Acute infectious emergencies in adults in medical practice].
AB  - Infectious diseases belong to the most frequent reasons to seek emergency care.
      Life-threatening infectious emergencies, which require rapid diagnosis and
      hospitalisation, are, however, rare. Leading signs and symptoms are high fever
      combined with rapidly deteriorating general conditions, hypotonia, tachycardia,
      tachypnea, dyspnea, confusion, headache, or petechia or information about
      asplenia, immunosuppression or recent travel to the tropics. Life threatening
      situations, such as suspicion of invasive meningococcal infection or bacterial
      infection in an asplenic patient, septic-toxic shock, and acute bacterial
      meningitis with delayed hospitalisation require rapid start of empiric antibiotic
      therapy in the outpatient practice. In addition, acute infectious emergencies
      comprise situation for which post exposure prophylaxis is indicated.

PMID- 15999932
TI  - [Emergencies in gynecology--what must I not forget?].
AB  - Emergency consultations happen frequently in gynaecology and may be due to
      abdominal pain, itching, utero-vaginal bleeding, rape, emergency contraception,
      insertion of foreign bodies, prolapse and urinary tract infection. Considering
      pregnancy in patients with child bearing potential is essential. Vaginal bleeding
      may be due to atrophy, infection, carcinoma or pregnancy. In the latter it is
      crucial to differentiate between ectopic, pathologic or physiologic pregnancy. In
      postmenopausal women further investigations by the gynaecologist are mandatory to
      exclude malignancy. Patients who have been raped need psychological, forensic and
      gynaecological support. Sexually transmitted disease including HIV must be
      considered and prophylactic drugs should be administered. If unprotected
      intercourse has occurred the "morning after pill" can be considered within 72
      hours after intercourse or an IUD up to five days. Prolapse occurs rarely as an
      acute problem but may induce urinary retention. Urinary tract infection is a
      common complaint and should be treated with antibiotics.

PMID- 15999933
TI  - [The urologic emergency--what should I not forget?].
AB  - The most frequently encountered urologic emergencies in daily practice include
      obstructive pyelonephritis, acute scrotal pain, acute urinary retention, urinary
      lithiasis and priapism. This article gives an overview on the pathogenesis,
      clinical presentation, diagnostic assessment and treatment strategies for each of
      these emergencies.

PMID- 15999934
TI  - [Endocrine crises].
AB  - Pituitary apoplexy, diabetes insipidus, thyroid storm, myxedema coma,
      parathyrotoxic crisis, hypocalcemia tetany, pheochromocytoma and Addison crisis,
      diabetic ketoacidosis, diabetic hyperosmolar nonketotic coma, hypoglycemia and
      carcinoid crisis are the most important endocrine crises. Some of them are
      common, others very rare. All physicians nevertheless need to have at least a
      basic knowledge of all of them, since symptoms and signs of endocrine crises
      overlap with those of other severe disease states, and the failure to recognise
      endocrine crises as such and to begin rapidly the specific therapy can have fatal
      consequences.

PMID- 15999935
TI  - [Acute chest pain--it's not always the heart! What additional laboratory and
      diagnostic imaging is needed].
AB  - Few diagnostic decisions in medicine have been more heavily researched and
      debated than the approach to patients with acute chest pain. In addition, the
      question is which patients with acute chest pain have a presentation benign
      enough to make discharge from the emergency department safe and appropriate
      despite the advances in diagnostic tests. There is always the possibility of
      missed diagnosis which may cause substantial morbidity and mortality. The use of
      algorithms or protocols is not always sufficient to avoid missed diagnosis and
      the individual physicians's diagnostic performance and clinical experience is as
      important as the best algorithm for atypical chest pain! Patients with atypical
      symptoms are most likely to be mistakenly discharged. This article does mainly
      focus on diagnostic tests including ECG and biomarkers such as troponin and D
      dimer as well as the investigation by helical CT scan in patients with suspected
      pulmonary embolism. The article also discuss the importance of repeated
      assessments of biomarkers and the determination of the exact time interval
      between the first clinical symptoms and the presentation to the emergency
      department. This time interval can be very crucial for the diagnostic work-up of
      patients with acute chest pain.

PMID- 15999936
TI  - [Acute dyspnea--what should I not forget?].
AB  - Acute dyspnea represents a diagnostic challenge even for the experienced
      physician. There are no prospectively evaluated diagnostic algorithms dealing
      with this frequent clinical problem. First of all, the emergency has to be
      assessed and life supporting measures have to be considered. In addition to a
      thorough medical history and clinical examination, chest X-ray, spirometry, ECG,
      hemoglobin measurement, BNP and D-dimer testing represent valuable diagnostic
      tools and are available to GP's. Most commonly, acute dyspnoea is pulmonary or
      cardiac in origin. Up to one third of all cases will have several causes.
      Functional dyspnea is difficult to diagnose but should be taken into
      consideration after excluding any somatic cause. Hyperventilation is found in
      both, organic and non organic diseases, and is therefore an inappropriate
      criterion to differentiate between the two. The mainstay in the management of any
      symptom is to primarily treat the underlying disease. A significant hypoxemia
      (SO2 < 90%, pO2 < 60 mmHg) ought to be corrected by supplemental oxygen. It is
      inappropriate to withhold oxygen from patients with COPD and severe hypoxemia
      just to avoid hypercapnia. Besides oxygen, opiates efficiently relief dyspnoea
      but harbour the risk of respiratory depression, altered mental status or
      aspiration.

PMID- 15999937
TI  - [Emergencies with the back and joints?].
AB  - General practitioners are frequently consulted for back and joint pain. Rarely,
      they are caused by serious diseases necessitating quick action to prevent
      complications such as irreversible neurological deficits or cartilage
      destruction. These include infections, haemorrhages and tumours, as well as
      diseases of various internal organs. A detailed history and physical examination
      provide red flags for specific causes of pain. In addition, synovia analyses
      allow differentiation between various causes of joint swelling. Finally, yellow
      flags point to exaggerated pain behaviour.

PMID- 15999938
TI  - [Psychiatric and psychosocial emergency situations].
AB  - Psychiatric emergencies and crises are unforseeable by nature and can have
      devastating consequences. They can arise both in the course of chronic mental
      illness and in people who had not shown any previous signs of mental illness.
      Conditions that are so similar that they might be confused with one another can
      be caused by a wide range of internal illnesses, adverse side-effects of
      medications or intoxication. This is the reason why establishing a psychiatric
      diagnosis in emergency situations must be primarily driven by the question as to
      whether the differential diagnosis is an internal illness or rather intoxication.
      The most prevalent psychiatric emergencies in clinical practice are nervous
      breakdowns, psychomotor agitation and violence, suicidal tendencies, delirium,
      psychoses as well as addictions.

PMID- 15999939
TI  - [Poisoning and drug emergency in practice].
AB  - Intoxicated patients make up 5-10% of all patients seen at emergency departments.
      The management of these patients is not always simple. Many of them are seen
      after ingestions of relatively non-toxic substances that require minimal medical
      care, intentional poisoning however often requires the highest standards of
      medical and nursing care and therefore the admission to an emergency department
      is mandatory. At admission, the involved substances are often not known since
      some of the patients are comatose. In such cases, the information from relatives
      and friends can be very crucial but to get hold of these sometimes essential
      "hints" is not always easy. Knowledge of the specific toxic agent allows the
      physician to plan a rational approach to the definitive management of the
      intoxicated patient after the vital functions have been stabilised. In some
      cases, very rare intoxications but with typical clinical signs do occur (e.g
      scromboid fish poisoning, coprinus-syndrome), which needs special diagnostic and
      therapeutic steps and a great deal of clinical experience. In most cases it is
      preferable to contact the Poison Control Center for additional advice.

PMID- 15999940
TI  - [The unusual cause of death--a special assignment for the doctor in emergency
      service].
AB  - The emergeny physician summoned to a sudden, unexpected death is confronted by
      various uncommon problems such as the certification of death on the "frontline"
      without destroying important evidence, the estimation of time since death,
      deciding whether the death must be reported to the authorities as well as taking
      care of mourning relatives. To all this questions the authors offer answers and
      practical advices.

PMID- 15999941
TI  - [Survived offenses of physical and sexual integrity--the responsibilities of the
      emergency physician].
AB  - The examination of living victims of physical and sexual assault as well as the
      documentation of injuries are tasks of the emergency physician. His observations
      and the documentation by photography, diagrams and description of findings are
      the basis for further legal proceedings. This article addresses the duties and
      responsibilities as well as the practical procedures of the physician regarding
      the announcement of incidents indicating crimes against the corporal and sexual
      integrity of patients to the authorities and the documentation of findings in
      general and addresses some special situations likely to occur in any medical
      emergency.

PMID- 15999942
TI  - [Problems concerning the general practitioner and emergencies--what should I not
      forget?].
AB  - BME and vocational training, legal, insurance, financial and social problems.
      Standards and guidelines, publicity, emergency equipment, emergencies in GP's
      office and at home, patient information, problems of elderly patient, ethical
      aspects. Some "key messages".

PMID- 15999943
TI  - Social anxiety disorder.

PMID- 15999944
TI  - Psychological treatments for social phobia.
AB  - OBJECTIVE: To review the empirical status of psychological treatments for social
      phobia (SP), commenting both on cognitive-behavioural interventions and on more
      recent iterations of those approaches. We also review the effective components of
      cognitive-behavioural therapy (CBT). METHOD: We qualitatively reviewed the
      empirical literature on the psychological treatment of SP. We include empirical
      studies, metaanalyses, and recent conference presentations in this review.
      RESULTS: Cognitive and behavioural interventions for SP appear to be more
      effective than wait-list controls and supportive therapy. Comparisons of CBT and
      pharmacologic treatment have produced inconsistent results. Several new
      treatments for SP demonstrate promising results. CONCLUSION: Evidence suggests
      that various psychosocial treatments for SP are better than wait-list controls
      and credible placebo interventions. Ongoing projects investigate the relative
      efficacy of combining medication and psychosocial treatments over monotherapies;
      this line of research is important to continue. Further research should also
      focus on which components of CBT are most effective.

PMID- 15999945
TI  - Are we overpathologizing the socially anxious? Social phobia from a harmful
      dysfunction perspective.

PMID- 15999946
TI  - Justifying the diagnostic status of social phobia: a reply to Wakefield, Horwitz,
      and Schmitz.
AB  - We believe that the harmful dysfunction model is important to consider when
      defining disorders. However, we question whether, when used in isolation, it
      provides an adequate basis for discriminating disorders from normal variations of
      temperament. We believe that it is important to consider the interaction between
      the individual's temperament and the demands of present-day society. We also
      assert that, when taken in the aggregate, the DSM-IV criteria for social phobia
      adequately establish the presence of harmful dysfunctions, particularly when
      significant impairment in one or more important domains of functioning is
      present. Finally, we argue that practical issues must be considered when we
      classify conditions as disorders. The fact that social phobia is classified as a
      legitimate disorder has undoubtedly spurred research efforts and encouraged
      countless individuals to seek relief for their suffering.

PMID- 15999948
TI  - Validation of a revised visual analog scale for premenstrual mood symptoms:
      results from prospective and retrospective trials.
AB  - OBJECTIVE: Previous studies have demonstrated that visual analog scales (VASs)
      are valid and reliable instruments for measuring the severity of premenstrual
      symptoms. Most of these studies, though, predate the introduction of DSM-IV
      diagnostic criteria for premenstrual dysphoric disorder (PMDD). Our objective was
      to assess the reliability and validity of VASs that were revised to better
      reflect the DSM-IV definition of PMDD. METHODS: Concurrent information from the
      well-validated Premenstrual Tension Syndrome-Observer (PMTS-O) rating scale was
      used to evaluate the revised VASs. Data from 4 randomized controlled trials (n =
      1208) evaluating the efficacy of paroxetine for the treatment of PMDD were used.
      Cronbach's alpha coefficient was used to evaluate the internal consistency of the
      core VAS mood items. Pearson's correlation between scores from the 2 scales was
      used to assess reliability. RESULTS: The internal consistency among the core VAS
      mood items (Cronbach's alpha > 0.90 across trials) was high. Luteal VAS scores
      and corresponding PMTS-O scores were moderately correlated at baseline (P <
      0.01). Luteal VAS change scores and corresponding PMTS-O change scores were
      strongly correlated (P < 0.01). These results did not differ regardless of
      whether the PMTS-O data were collected prospectively or retrospectively.
      CONCLUSION: The revised VASs, which approximate the current DSM-IV definition of
      PMDD, provide a valid and reliable measure of the severity of premenstrual
      symptoms when evaluated against the validated PMTS-O scale. Our results also
      suggest that, whether observers assessed severity of PMDD symptoms
      retrospectively or prospectively using the PMTS-O scale, the correlations with
      the patient-reported VAS scores were comparable.

PMID- 15999949
TI  - Predictors of professional and personal satisfaction with a career in psychiatry.
AB  - BACKGROUND: Many factors, including personal experience and personality traits,
      contribute to the emotional difficulties that psychiatrists experience in their
      professional work. The nature of the work itself also plays a significant role.
      OBJECTIVE: To determine those personal and professional characteristics that
      predict satisfaction with the practice of psychiatry. METHOD: We mailed a
      questionnaire that included items pertaining to aspects of personal and
      professional life to the entire population of psychiatrists in Ontario (N =
      1574). RESULTS: Of the 1574, 52% (n = 802) responded. We conducted a series of
      regression analyses to determine factors related to career satisfaction or
      regret. A belief in the intrinsic value of psychiatry, a low perceived degree of
      emotional burden from patients, financial success, and satisfaction with
      psychotherapeutic work emerged consistently as significant predictors. A
      subsequent discriminant function analysis indicated that all 4 of these variables
      accurately predicted those psychiatrists with extreme satisfaction or
      dissatisfaction with work. CONCLUSIONS: These results reveal several variables
      associated with career satisfaction in the practice of psychiatry that might be
      useful to discuss with residents who are beginning their careers.

PMID- 15999950
TI  - Are dexamethasone suppression test nonsuppression and thyroid dysfunction related
      to a family history of dementia in patients with major depression? An exploratory
      study.
AB  - OBJECTIVE: Recent data suggest that the low thyroid function syndrome in
      depression is nonspecific. They also suggest that depression may constitute a
      risk factor for the development of dementia, especially in atypical patients who
      have high rates of hypothalamo-pituitary-adrenal axis disorders. This study aimed
      to search for correlations among Dexamethasone Suppression Test (DST) cortisol
      levels, thyroid indices, and family history of dementia in patients with
      depression. METHODS: A sample of 30 patients, aged 21 to 60 years and suffering
      from major depression according to DSM-IV criteria, took part in the study. Three
      had a family history of dementia in first-degree relatives. We measured their
      serum levels of free T3, free T4, thyroid-stimulating hormone, thyroid binding
      inhibitory immunoglobulines, thyroglobulin antibodies, and thyroid microsomal
      antibodies (TMAs). We applied the 1-mg DST to all patients. The statistical
      analysis included 1-way multivariate analysis of covariance using t tests as the
      post hoc tests. RESULTS: Significantly higher levels of TMAs were found in
      patients with a family history of dementia, compared with those who did not have
      this family history. CONCLUSION: The results of this study suggest that a more
      pronounced autoimmune process may characterize depression patients with a family
      history of dementia.

PMID- 15999951
TI  - Prevalence of depression and prescriptions for antidepressants, Bella Coola
      Valley, 2001.
AB  - OBJECTIVE: To determine the prevalence of depression-anxiety disorders and the
      degree to which physicians prescribed antidepressants for Aboriginal and non
      Aboriginal populations living in a remote rural community in British Columbia in
      2001. METHODS: To obtain data for our main outcome measures, we retrospectively
      reviewed the charts of 2375 patients living in the Bella Coola Valley as of
      September 2001 and attending the Bella Coola Medical Clinic. RESULTS: The 2001
      prevalence rate of depression-anxiety disorders in the Bella Coola Valley was
      7.5% (177/2375). Depression was the most common problem (86%) in these patients.
      Women had a higher rate of depression-anxiety disorders (10.3%) than did men
      (4.7%) (P < 0.001). Non-Aboriginal people had a slightly higher rate (8.5%) than
      did Aboriginal people (6.3%); however, the difference was not statistically
      significant. Antidepressant medications were commonly prescribed for chronic pain
      and insomnia. The general pattern of antidepressant medication use in 2001 among
      both Aboriginal and non-Aboriginal people living in the Bella Coola Valley was as
      follows: peak use of antidepressants was in the middle to late years; the rate
      for women was roughly double the rate for men; and proportionately more
      Aboriginal people, especially the women, were taking antidepressants.
      CONCLUSIONS: Depression-anxiety disorder prevalence rates for Aboriginal and non
      Aboriginal populations are similar. When using antidepressant medication
      prescriptions as a community health indicator, health care administrators should
      be aware that antidepressant medications are commonly prescribed for conditions
      other than depression-anxiety disorder.

PMID- 15999952
TI  - Suicide ideation in different generations of immigrants.
AB  - OBJECTIVE: To identify whether pressures associated with acculturation are
      related to suicide ideation. METHOD: We assessed 1135 undergraduates, using
      suicide measures and the Vancouver Index of Acculturation. RESULTS AND
      CONCLUSIONS: Suicide ideation, plans, and attempts did not vary by generation
      level or with mainstream acculturation for any of the ethnic groups studied
      (European, Chinese, and Indo-Asian), nor did they vary among ethnic groups. The
      results indicate that individuals who identified closely with their heritage
      culture were at an increased risk for suicidal thoughts but not for suicide plans
      or attempts.

PMID- 15999953
TI  - Ropinirole in treatment-resistant depression: a 16-week pilot study.
AB  - OBJECTIVE: The study aimed to assess the antidepressant efficacy and tolerability
      of adjunctive ropinirole in outpatients with treatment-resistant depression
      (TRD). METHOD: The study sample consisted of patients with a major depressive
      episode (diagnosed according to DSM-IV criteria) and TRD. Ropinirole 0.25 to 1.5
      mg daily was added to tricyclic antidepressants or selective serotonin reuptake
      inhibitors. We conducted assessments at baseline and at weeks 2, 4, 8, 12, and
      16. We defined response as a 50% or greater reduction of the Montgomery-Asberg
      Depression Rating Scale (MADRS) total score plus a score of 1 ("very much
      improved") or 2 ("much improved") on the Clinical Global Impression of
      Improvement scale at endpoint. Tolerability was monitored with the Dosage Record
      Treatment Emergent Symptom Scale. RESULTS: Seven patients had major depressive
      disorder, and 3 had bipolar II disorder. The mean maximum dose of ropinirole was
      1.33 mg daily. Mean (SD) scores on the MADRS decreased from 29.6 (7.6) at
      baseline to 16.9 (12.1) at endpoint (P < 0.02). At endpoint, 4 of 10 (40%)
      patients were responders. Two patients discontinued ropinirole because of
      dizziness. CONCLUSIONS: These pilot data suggest that, in selected cases of TRD,
      ropinirole augmentation of antidepressants is effective and relatively well
      tolerated.

PMID- 15999954
TI  - Nightmares and serum cholesterol level: a preliminary report.
AB  - OBJECTIVE: To examine whether there is a relation between nightmares and serum
      lipid levels. METHODS: Fifteen subjects who met DSM-IV criteria for the diagnosis
      of nightmare disorder and 15 healthy control subjects participated in the study.
      We used an enzymatic colorimetric method for cholesterol and triglyceride
      determination. We measured high-density lipoprotien (HDL) cholesterol using the
      direct HDL-cholesterol method. Low-density lipoprotein (LDL) was calculated
      according to the Friedewald formula. RESULTS: Patients with nightmare disorder
      had lower serum triglyceride, lower total cholesterol, and lower LDL levels than
      healthy control subjects. CONCLUSION: These findings suggest that nightmares are
      associated with low serum lipid levels.

PMID- 15999955
TI  - Rabbit syndrome induced by combined lithium and risperidone.

PMID- 15999956
TI  - [Combination of personality disorders among male prisoners].

PMID- 15999957
TI  - Decreasing mortality for patients undergoing hip fracture repair surgery.
AB  - BACKGROUND: Staten Island University Hospital (Staten Island, New York) undertook
      an initiative to reduce mortality in a high-risk population on the basis of
      findings from a root cause analysis (RCA). METHODS: A 78-year-old woman admitted
      following a fall was diagnosed with a femur fracture. The medical history was
      significant for chronic obstructive pulmonary disease, hypothyroidism, and
      laryngeal cancer. A medical consultant classified the patient as grade II
      (American Society of Anaesthesiologists-Physical Status [ASA] scale), no contra
      indication for operating room (OR). An anesthesiologist evaluated the patient as
      an ASA grade III/IV. The patient went to the OR and died after anesthesia
      induction. The RCA revealed inadequate communication between providers and
      preoperative assessment and no framework to privilege providers for high risk
      preoperative evaluations. Proposed corrective actions included use of a
      preoperative assessment tool. RESULTS: During the baseline year, 2000, the
      preimplementation mortality rate for 185 patients undergoing hip fracture repair
      surgery was 4.9%. For the 644 postimplementation patients, the mortality rate
      decreased to 2.7% for both 2001 and 2002 and to 1% for 2003. Comparison of the
      2000 baseline and 2003 mortalities indicated a statistically significant
      mortality reduction of 79% (p = .0245). DISCUSSION: Mortality rates can be
      reduced by systematic application of comprehensive preoperative assessment when
      implemented by specially trained and privileged staff.

PMID- 15999958
TI  - Intensive glycemic management in critically ill patients.
AB  - BACKGROUND: The effect of an intensive glycemic management protocol was assessed
      in a heterogeneous population of critically ill adult patients. METHODS: Patients
      representing 800 consecutive admissions following the institution of the protocol
      were compared with the 800 admissions immediately preceding the institution of
      the protocol in a 14-bed mixed medical-surgical intensive care unit (ICU). The
      protocol used intensive monitoring and treatment to maintain blood glucose values
      >140 mg/dl. Continuous intravenous insulin was used if glucose values were >200
      mg/dl on two successive occasions. RESULTS: Mean glucose decreased from 152.3
      mg/dl to 130.7 mg/dl (p < .001), marked by a 56.3% reduction in the percentage of
      glucose values > or =200 mg/dl, without a significant change in hypoglycemia.
      There were decreases in the development of new renal insufficiency (p = .034) and
      in the number of patients receiving transfusion of packed red blood cells (p =
      .035) during the protocol period. Hospital mortality decreased 29.3% (p = .002),
      and ICU length of stay decreased 10.8% (p = .011) after institution of the
      protocol. DISCUSSION: The 29.3% relative reduction in hospital mortality seen
      among the treatment patients following institution of the protocol probably
      exceeded the expectations of the initiative's champions. The culture of the ICU
      regarding glycemic control changed definitively. The protocol was extended to an
      intermediate care unit, resulting in improvement in glycemic control without an
      increase in hypoglycemia.

PMID- 15999959
TI  - Reduction in anticoagulation-related adverse drug events using a trigger-based
      methodology.
AB  - BACKGROUND: An initiative was undertaken by Novant Health System to address
      warfarin-related adverse drug events (ADEs) using lab-based patient-specific
      International Normalized Ratio (INR) triggers and pharmacy-based patient-specific
      Vitamin K triggers. The goal was to reduce ADEs related to the use of warfarin in
      both the inpatient and outpatient settings. Process improvements and medication
      management protocols were developed for patients managed with warfarin
      anticoagulation. METHODS: During each month's seven-day sampling period, the
      hospital information system generated the lab and pharmacy triggers, and the
      clinical pharmacists used these patient-specific triggers to identify the patient
      charts for review. All triggered charts were reviewed. Preliminary harm
      classification based on the National Coordinating Council for Medication Error
      Reporting and Prevention (NCC MERP) index was assigned by the clinical
      pharmacists and recorded for each patient. RESULTS: The system achieved
      reductions in ADEs related to warfarin administration on an inpatient management
      (45%) and outpatient management (52%) basis. DISCUSSION: Although based on
      inpatient facility-generated triggers, the initiative also served as a reasonable
      outpatient model, with improvements seen in the outpatient physician intervention
      groups.

PMID- 15999960
TI  - Using Six Sigma to reduce medication errors in a home-delivery pharmacy service.
AB  - BACKGROUND: Medco Health Solutions, Inc. conducted a project to reduce medication
      errors in its home-delivery service, which is composed of eight prescription
      processing pharmacies, three dispensing pharmacies, and six call-center
      pharmacies. IMPLEMENTING THE PROJECT: Medco uses the Six Sigma methodology to
      reduce process variation, establish procedures to monitor the effectiveness of
      medication safety programs, and determine when these efforts do not achieve
      performance goals. A team reviewed the processes in home-delivery pharmacy and
      suggested strategies to improve the data-collection and medication-dispensing
      practices. A variety of improvement activities were implemented, including a
      procedure for developing, reviewing, and enhancing sound-alike/look-alike (SALA)
      alerts and system enhancements to improve processing consistency across the
      pharmacies. RESULTS: "External nonconformances" were reduced for several
      categories of medication errors, including wrong-drug selection (33%), wrong
      directions (49%), and SALA errors (69%). Control charts demonstrated evidence of
      sustained process improvement and actual reduction in specific medication error
      elements. DISCUSSION: Establishing a continuous quality improvement process to
      ensure that medication errors are minimized is critical to any health care
      organization providing medication services.

PMID- 15999961
TI  - Reducing adolescent clients' anger in a residential substance abuse treatment
      facility.
AB  - BACKGROUND: Sundown Ranch, a residential behavioral health care treatment
      facility for adolescents, tracked the progress and results of treatment by
      selecting performance measures from a psychosocial screening inventory. The
      temper scale was one of the two highest scales at admission and the highest scale
      at discharge. A clinical performance improvement (PI) project was conducted to
      assess improvements in clients' ability to manage anger after the incorporation
      of Rational Emotive Behavior Therapy (REBT) into treatment. METHODS: Eighteen
      months of baseline data (July 1, 1999 - February 1, 2001) were collected, and 20
      months of data (May 1, 2001 - December 31, 2002) were collected after the
      introduction of the PI activity. In all, data were collected for 541 consecutive
      admissions. RESULTS: A comparison of five successive quarterly reviews indicated
      average scores of 1.4 standard deviations (SDs) above the mean on the temper
      scale before the PI activity and .45 SD above the mean after. The performance
      threshold of reduction of the average temper scale score to < or =1 SD was met
      for 17 of 20 months. DISCUSSION: The fact that the PI activity reduced the temper
      scale elevations by almost one full SD is highly suggestive of the efficacy of
      REBT with the treatment population. After the project was completed, REBT was
      promoted as an additional therapeutic modality within the treatment program.

PMID- 15999962
TI  - Developing an end-of-life program for long term care residents.
AB  - BACKGROUND: An end-of-life program, the Butterflies Are Free Program, was
      developed at Life Care Center, a long term care facility in Sarasota, Florida to
      provide residents with comfort and dignity during the end stage of life. PI TEAM:
      A PI team identified the goal: "Establish an end-of-life program that maintains
      comfort and dignity for the resident involving the family, residents, and staff
      in the plan of care at their personal level of comfort. The end-of-life program
      should put no financial strain on the family." The program entailed involving the
      resident and family in the end-of-life care plan, which included consideration,
      for example, of pain medications, spiritual support, and continuing or
      discontinuing routine medications. The project team began meeting in August 2002,
      and the program was formally implemented in December 2002. RESULTS: A
      preintervention (control group), which covered 11 months, was compared with a
      2003 postintervention group, which covered 13 months. Data indicated that the
      number of residents receiving pain medication during the dying process increased
      by 27.3%. The facility team members received thank you notes and cards from 41%
      of the families whose loved one died. The initiative reduced the out-of-pocket
      expenses to the dying resident and their family by 48%. DISCUSSION: Review of the
      2003 data prompted the development of new goals for 2004 and a refinement of the
      end-of-life program. This program could be easily duplicated in any long term
      care facility.

PMID- 15999963
TI  - Managing unnecessary variability in patient demand to reduce nursing stress and
      improve patient safety.
AB  - BACKGROUND: Increases in adverse clinical outcomes have been documented when
      hospital nurse staffing is inadequate. Since most hospitals limit nurse staffing
      to levels for average rather than peak patient census, substantial census
      increases create serious potential stresses for both patients and nurses. By
      reducing unnecessary variability, hospitals can reduce many of these stresses and
      thereby improve patient safety and quality of care. THE SOURCE AND NATURE OF
      VARIABILITY IN DEMAND: The variability in the daily patient census is a
      combination of the natural (uncontrollable) variability contributed by the
      emergency department and the artificial (potentially controllable) peaks and
      valleys of patient flow into the hospital fromelective admissions. Once
      artificial variability in demand is significantly reduced, a substantial portion
      of the peaks and valleys in census disappears; the remaining censsus variability
      is largely patient and disease driven. When artificial variability has been
      minimized, a hospital must have sufficient resources for the remaining patient
      driven peaks in demand, over which it has no control, if it is to deliver an
      optimal level of care. DISCUSSION: Study of operational issues in health care
      delivery, and acting on what is learned, is critical. Al forms of artificial
      variation in the demand and supply of health care services should be identified,
      and pilot programs to test operational changes should be conducted.

PMID- 15999964
TI  - Using a framework for spread: The case of patient access in the Veterans Health
      Administration.
AB  - BACKGROUND: Experience indicates that an effective operational system will spread
      much more slowly than, for example, a new antinausea drug. The Veterans Health
      Administration (VHA) used a Framework for Spread to spread improvements in access
      to more than 1800 outpatient clinics between April 2001 and December 2003. The
      framework identifies strategies and methods for planning and guiding the spread
      of new ideas or new operational systems, including the responsibilities of
      leadership, packaging the new ideas, communication, strengthening the social
      system, measurement and feedback, and knowledge management. APPLYING THE
      FRAMEWORK FOR SPREAD: Following a collaborative for reducing waiting times for
      patients without the large-scale addition of resources, each of the participating
      22 Veterans Integrated Service Networks (VISNs) used the framework to expand
      improvements in access to care to six additional targeted clinics (for example,
      primary care, eye care, cardiology). RESULTS: During the VHAs spread initiative,
      waiting time for a primary care appointment decreased from 60.4 days at the end
      of fiscal year (FY) 2000 to 28.4 at the end of FY 2002. Results were sustained.
      Waiting time was <25 days at the end of FY 2004. DISCUSSION: The Framework for
      Spread suggests areas that organizations should consider when developing and
      executing a strategy for a spread initiative. Further study is needed to
      determine the specific activities that should be emphasized to accelerate spread.

PMID- 15999965
TI  - Medication errors involving pediatric patients.

PMID- 15999966
TI  - AHRQ quality and safety initiatives.

PMID- 15999967
TI  - Accuracy in the assessment of return on investment of defined population
      interventions.

PMID- 15999968
TI  - [Risk factors of coronary artery syndrome are significant all the way from
      childhood].

PMID- 15999969
TI  - [Are we prepared for biological threat?].

PMID- 15999970
TI  - [Lyme disease].

PMID- 15999971
TI  - [Congenital hyperinsulinism].

PMID- 15999972
TI  - [Nontuberculous mycobacterial diseases--difficult to diagnose and difficult to
      treat].

PMID- 15999973
TI  - [Muscle weakness, pain, vision disorders, all symptoms of lead poisoning].

PMID- 15999974
TI  - [Odd bumps on the head].

PMID- 15999975
TI  - [Is it too early to market the two-step screening method for dyspepsia
      patients?].

PMID- 15999976
TI  - [Sweet Talk].

PMID- 15999977
TI  - [Calcified aortic valve stenosis, could the process be prevented?].

PMID- 15999978
TI  - [How to make scar tissue in cardiac muscle beat?].

PMID- 15999979
TI  - [Stroke and foramen ovale. The hypothesis of paradoxal embolization is still
      without proof].

PMID- 15999980
TI  - [Catheterization in the care of congenital heart disease].

PMID- 15999981
TI  - [Mechanical devices in the treatment of severe heart failure].

PMID- 15999982
TI  - [Prevention of restenosis after coronary stenting, problem soon resolved].

PMID- 15999983
TI  - [Drug treatment of heart failure].

PMID- 15999984
TI  - [Catheter ablation for ventricular tachycardia].

PMID- 15999985
TI  - Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a
      putative meiosis-related protein.
AB  - Transcripts with ESTs derived exclusively or predominantly from testis, and not
      from other normal tissues, are likely to be products of genes with testis
      restricted expression, and are thus potential cancer/testis (CT) antigen genes. A
      list of 371 genes with such characteristics was compiled by analyzing publicly
      available EST databases. RT-PCR analysis of normal and tumor tissues was
      performed to validate an initial selection of 20 of these genes. Several new CT
      and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed
      strongly in testis and weakly in placenta; the highest level of expression in
      other tissues is <1% of testicular expression. The CT46/HORMAD1 gene was
      expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing
      expression levels >10% of the testicular level of expression. CT46/HORMAD1 is a
      single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa.
      Conserved protein domain analysis identified a HORMA domain involved in chromatin
      binding. The CT46/HORMAD1 protein was found to be homologous to the prototype
      HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well
      as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.

PMID- 15999986
TI  - p53 Activation by small molecules: application in oncology.

PMID- 15999987
TI  - [Nalpha-benzylTyr1,cyclo(D-Asp5,Dap8)]- dynorphin A-(1-11)NH2 cyclized in the
      "address" domain is a novel kappa-opioid receptor antagonist.
AB  - The cyclic dynorphin A analogue [N(alpha)-benzylTyr(1),cyclo(D
      Asp(5),Dap(8))]dynorphin A-(1-11)NH(2) (Dap = 2,3-diaminopropionic acid) exhibits
      nanomolar affinity (30 nM) and high selectivity (K(i) ratio (kappa/mu/delta) =
      1/194/330) for kappa-opioid receptors. This analogue antagonizes dynorphin A-(1
      13)NH(2) at kappa-opioid receptors in the adenylyl cyclase assay (K(B) = 84 nM).
      This is the first dynorphin A-based antagonist with modifications in the C
      terminal "address" domain that alter efficacy and thus represents a novel
      selective kappa-opioid receptor antagonist.

PMID- 15999988
TI  - Highly stable phenanthridinium frameworks as a new class of tunable DNA binding
      agents with cytotoxic properties.
AB  - A new class of cytotoxic heteroaromatic cations is presented, based on the
      dihydro-imidazo-phenanthridinium framework (DIP), that have affinity for DNA and
      cytotoxicity toward cancerous cells. The DIP framework is particularly tunable
      due to the flexible synthetic methodology. Furthermore, the central moiety has
      proved to be very stable to hydrolysis and reduction compared to other
      phenanthridinium-based agents.

PMID- 15999990
TI  - Probing the subpockets of factor Xa reveals two binding modes for inhibitors
      based on a 2-carboxyindole scaffold: a study combining structure-activity
      relationship and X-ray crystallography.
AB  - Structure-activity relationships within a series of highly potent 2-carboxyindole
      based factor Xa inhibitors incorporating a neutral P1 ligand are described with
      particular emphasis on the structural requirements for addressing subpockets of
      the factor Xa enzyme. Interactions with the subpockets were probed by systematic
      substitution of the 2-carboxyindole scaffold, in combination with privileged P1
      and P4 substituents. Combining the most favorable substituents at the indole
      nucleus led to the discovery of a remarkably potent factor Xa inhibitor
      displaying a K(i) value of 0.07 nM. X-ray crystallography of inhibitors bound to
      factor Xa revealed substituent-dependent switching of the inhibitor binding mode
      and provided a rationale for the SAR obtained. These results underscore the key
      role played by the P1 ligand not only in determining the binding affinity of the
      inhibitor by direct interaction but also in modifying the binding mode of the
      whole scaffold, resulting in a nonlinear SAR.

PMID- 15999989
TI  - Design and synthesis of new nonsteroidal glucocorticoid modulators through
      application of an "agreement docking" method.
AB  - Structurally related glucocorticoid receptor (GR) binders were docked into the GR
      active site to select the binding mode closest to the true docking mode. This
      process, termed an "agreement docking method", led to the design of
      tetrahydronaphthalene 9. The method was validated by the syntheses of 9 and
      related analogues, which are potent binders of GR. 15a is a partial agonist while
      9e and 15a are micromolar antagonists in a mouse mammary tumor virus
      transactivation assay.

PMID- 15999991
TI  - Synthesis and biological evaluation of geminal disulfones as HIV-1 integrase
      inhibitors.
AB  - Integration of HIV-1 viral DNA into the host genome is carried out by HIV
      integrase (IN) and is a critical step in viral replication. Although several
      classes of compounds have been reported to inhibit IN in enzymatic assays,
      inhibition is not always correlated with antiviral activity. Moreover, potent
      antiviral IN inhibitors such as the chicoric acids do not act upon the intended
      enzymatic target but behave as entry inhibitors instead. The charged nature of
      the chicoric acids contributes to poor cellular uptake, and these compounds are
      further plagued by rapid ester hydrolysis in vivo. To address these critical
      deficiencies, we designed neutral, nonhydrolyzable analogues of the chicoric
      acids. Herein, we report the synthesis, enzyme inhibition studies, and cellular
      antiviral data for a series of geminal disulfones. Of the 10 compounds evaluated,
      8 showed moderate to high inhibition of IN in purified enzyme assays. The
      purified enzyme data correlated with antiviral assays for all but two compounds,
      suggesting alternative modes of inhibition. Time-of-addition studies were
      performed on these analogues, and the results indicate that they inhibit an early
      stage in the replication process, perhaps entry. In contrast, the most potent
      member of the correlative group shows behavior consistent with IN being the
      cellular target.

PMID- 15999992
TI  - Synthesis and identification of [1,3,5]triazine-pyridine biheteroaryl as a novel
      series of potent cyclin-dependent kinase inhibitors.
AB  - On the basis of previous studies, we identified pyrazine-pyridine A as a potent
      vascular endothelial growth factor inhibitor and pyrimidine-pyridine B as a
      moderately potent cyclin dependent kinase (CDK) inhibitor. A proposed combination
      of CGP-60474 and compound B led to the discovery of [1,3,5]triazine-pyridine as a
      new series of potent CDK inhibitors. Palladium-catalyzed C-C bond formation
      reactions, particularly the Negishi coupling reaction, were used to assemble
      various triazine-heteroaryl analogues effectively. Among them, compound 20
      displayed high inhibitory potency at CDK1 (IC(50) = 0.021 microM), CDK2, and CDK5
      and submicromolar potency at CDK4, CDK6, and CDK7. Compound 20 also displayed
      high potency at GSK-3beta. It demonstrated potent antiproliferative activity on
      various tumor cell lines, including HeLa, HCT-116, U937, and A375. When 20 was
      administered intraperitoneally at 150 and 125 mg/kg to nude mice bearing human
      A375 xenografts, the compound produced a significant survival increase. Molecular
      docking studies were conducted in an attempt to enhance the understanding of the
      observed structure-activity relationship.

PMID- 15999993
TI  - Potent inhibitors of subgenomic hepatitis C virus RNA replication through
      optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B
      polymerase.
AB  - Infections caused by hepatitis C virus (HCV) are a significant world health
      problem for which novel therapies are in urgent demand. Compounds that block
      replication of subgenomic HCV RNA in liver cells are of interest because of their
      demonstrated antiviral effect in the clinic. In followup to our recent report
      that indole-N-acetamides (e.g., 1) are potent allosteric inhibitors of the HCV
      NS5B polymerase enzyme, we describe here their optimization as cell-based
      inhibitors. The crystal structure of 1 bound to NS5B was a guide in the design of
      a two-dimensional compound array that highlighted that formally zwitterionic
      inhibitors have strong intracellular potency and that pregnane X receptor (PXR)
      activation (an undesired off-target activity) is linked to a structural feature
      of the inhibitor. Optimized analogues devoid of PXR activation (e.g., 55, EC(50)
      = 127 nM) retain strong cell-based efficacy under high serum conditions and show
      acceptable pharmacokinetics parameters in rat and dog.

PMID- 15999994
TI  - Large-scale validation of a quantum mechanics based scoring function: predicting
      the binding affinity and the binding mode of a diverse set of protein-ligand
      complexes.
AB  - Computational methods to calculate binding affinity in protein-ligand interaction
      are of immense interest because of obvious practical applications in structure
      based drug design. Scoring functions attempt to calculate the variation in
      binding affinity of ligands-inhibitors bound to protein targets at various levels
      of theory. In this study we use semiempirical quantum mechanics to design a
      scoring function that can calculate the electrostatic interactions and solvation
      free energy expected during complexation. This physically based approach has the
      ability to capture binding affinity trends in a diverse range of protein-ligand
      complexes. We also show the predictive power of this scoring function within
      protein targets and its ability to score ligand poses docked to a protein target.
      We also demonstrate the ability of this scoring function to discriminate between
      native and decoy poses and highlight the crucial role played by electrostatic
      interactions in molecular recognition. Finally we compare the performance of our
      scoring function with other available scoring functions in the literature.

PMID- 15999995
TI  - Adamantyl cannabinoids: a novel class of cannabinergic ligands.
AB  - Structure-activity relationship studies have established that the aliphatic side
      chain plays a pivotal role in determining the cannabinergic potency of tricyclic
      classical cannabinoids. We have now synthesized a series of analogues in which a
      variety of adamantyl substituents were introduced at the C3 position of Delta(8)
      THC. Our lead compound, (-)-3-(1-adamantyl)-Delta(8)-tetrahydrocannabinol (1a,
      AM411), was found to have robust affinity and selectivity for the CB1 receptor as
      well as high in vivo potency. The X-ray crystal structure of 1a was determined.
      Exploration of the side chain conformational space using molecular modeling
      approaches has allowed us to develop cannabinoid side chain pharmacophore models
      for the CB1 and CB2 receptors. Our results suggest that although a bulky group at
      the C3 position of classical cannabinoids could be tolerated by both CB1 and CB2
      binding sites, the relative orientation of that group with respect to the
      tricyclic component can lead to receptor subtype selectivity.

PMID- 15999996
TI  - Identification of novel extracellular signal-regulated kinase docking domain
      inhibitors.
AB  - The extracellular signal regulated kinase (ERK1 and ERK2) signal transduction
      pathways play a critical role in cell proliferation. Hyperactivation of the ERK
      proteins either through increased expression of membrane-bound growth factor
      receptors or genetic mutations of upstream proteins is thought to be involved in
      the pathogenesis of many human cancers. Thus, targeted inhibition of ERK
      signaling is viewed as a potential approach to prevent cancer cell proliferation.
      Currently, no specific inhibitors of the ERK proteins exist. Moreover, most
      kinase inhibitors lack specificity because they target the ATP binding region,
      which is well conserved among the protein kinase families. Taking advantage of
      recently identified ERK docking domains, which are reported to facilitate
      substrate protein interactions, we have used computer-aided drug design (CADD) to
      identify novel small molecular weight ERK inhibitors. Following a CADD screen of
      over 800 000 molecules, 80 potential compounds were selected and tested for
      activity in biological assays. Several compounds inhibited ERK-specific
      phosphorylation of ribosomal S6 kinase-1 (Rsk-1) or the ternary complex factor
      Elk-1 (TCF/Elk-1), both of which are involved in promoting cell proliferation.
      Active compounds showed a dose-dependent reduction in the proliferation of
      several cancer cell lines as measured by colony survival assays. Direct binding
      between the active compounds and ERK2 was indicated by fluorescence quenching.
      These active compounds may serve as lead candidates for development of novel
      specific inhibitors of ERK-substrate interactions involved in cell proliferation.

PMID- 15999997
TI  - Design and synthesis of the first generation of novel potent, selective, and in
      vivo active (benzothiazol-2-yl)acetonitrile inhibitors of the c-Jun N-terminal
      kinase.
AB  - Several lines of evidence support the hypothesis that c-Jun N-terminal kinase
      (JNKs) plays a critical role in a wide range of diseases including cell death
      (apoptosis)-related disorders (neurodegenerative diseases, brain, heart, and
      renal ischemia, epilepsy) and inflammatory disorders (multiple sclerosis,
      rheumatoid arthritis, inflammatory bowel diseases). Screening of our internal
      compound collection for inhibitors of JNK3 led to the identification of
      (benzothiazol-2-yl)acetonitrile derivatives as potent and selective JNK1, -2, -3
      inhibitors. Starting from initial hit 1 (AS007149), the chemistry and initial
      structure-activity relationship (SAR) of this novel and unique kinase inhibitor
      template were explored. Investigation of the SAR rapidly revealed that the
      benzothiazol-2-ylacetonitrile pyrimidine core was crucial to retain a good level
      of potency on rat JNK3. Therefore, compound 6 was further optimized by exploring
      a number of distal combinations in place of the chlorine atom. This led to the
      observation that the presence of an aromatic group, two carbons away from the
      aminopyrimidine moiety and bearing substituents conferring hydrogen bond acceptor
      (HBA) properties, could improve the potency. Further improvements to the
      biological and biopharmaceutical profile of the most promising compounds were
      performed, resulting in the discovery of compound 59 (AS601245). The in vitro and
      in vivo anti-inflammatory potential of this new JNK inhibitor was investigated
      and found to demonstrate efficacy per oral route in an experimental model of
      rheumatoid arthritis (RA).

PMID- 15999998
TI  - Synthesis and immunosuppressive activity of new artemisinin derivatives. 1.
      [12(beta or alpha)-Dihydroartemisininoxy]phen(ox)yl aliphatic acids and esters.
AB  - A series of novel dihydroartemisinin derivatives were synthesized and evaluated
      on their immunosuppressive activity in the search for potential immunosuppressive
      agents with high efficacy and low toxicity. These compounds were assayed in their
      cytotoxicity of lymphocyte, inhibition activity on concanavalin A (ConA) induced
      T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation.
      Among them, 11b, 13b, 14d, 15b, 16, and 17 remarkably exhibited lower
      cytotoxicity and higher inhibition activity on the mitogen-induced T cell and B
      cell proliferation in comparison with artemisinin, artesunate, and artemether in
      vitro. More significantly, compound 11b displayed reduced cytotoxicity by over
      100-fold compared with cyclosporin A (CsA) and comparable inhibition activity (SI
      = 848) on ConA-induced T cell proliferation to CsA (SI = 963) and more than 4000
      times the inhibitory effect (SI = 28473) on LPS-induced B cell proliferation
      compared with CsA (SI = 7) in vitro. The in vivo experimental results showed that
      compound 16 could inhibit 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type
      hypersensitivity (DTH) reaction and sheep red blood cell (SRBC) induced antibody
      production, respectively. The structure and activity relationships (SAR) of these
      compounds were also discussed.

PMID- 15999999
TI  - Novel alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor
      antagonists of 2,3-benzodiazepine type: chemical synthesis, in vitro
      characterization, and in vivo prevention of acute neurodegeneration.
AB  - Under pathophysiological conditions, alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA) receptor activation is considered to play a key role in several
      disorders of the central nervous system. In the search for AMPA receptor
      antagonists, the synthesis and pharmacological characterization of a series of
      novel compounds that are structurally related to GYKI 52466 (1), a well-known
      selective noncompetitive AMPA receptor antagonist, was performed. In vitro, 2,3
      dimethyl-6-phenyl-12H-[1,3]dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine (ZK
      187638, 14a) antagonized the kainate-induced currents in cultured hippocampal
      neurons with an IC(50) of 3.4 microM in a noncompetitive fashion. When tested in
      a clinically predictive rat model of acute ischemic stroke, this noncompetitive
      AMPA receptor antagonist significantly reduced brain infarction, indicating that
      it is neuroprotective after permanent focal cerebral ischemia.

PMID- 16000000
TI  - Synthesis and structure-activity relationships of soluble 7-substituted 3-(3,5
      dimethoxyphenyl)-1,6-naphthyridin-2-amines and related ureas as dual inhibitors
      of the fibroblast growth factor receptor-1 and vascular endothelial growth factor
      receptor-2 tyrosine kinases.
AB  - 7-Substituted 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas are
      inhibitors of fibroblast growth factor receptor-1 (FGFR-1) and vascular
      endothelial growth factor receptor-2 (VEGFR-2). 3-(3,5-Dimethoxyphenyl) and 3
      phenyl analogues were prepared from 7-acetamido-2-tert-butylureas by alkylation
      with benzyl omega-iodoalkyl ethers, debenzylation, and amination, followed by
      selective cleavage of the 7-N-acetamide. 3-(2,6-Dichlorophenyl) analogues were
      prepared from the 7-fluoro-2-amine by displacement with substituted alkylamines,
      followed by selective acylation of the resulting substituted naphthyridine-2,7
      diamines with alkyl isocyanates. The 3-(3,5-dimethoxyphenyl) derivatives were low
      nanomolar inhibitors of both FGFR and VEGFR and were highly selective (>100-fold)
      over PDGFR and c-Src. Variations in the base strength or spatial position of the
      7-side chain base had only small effects on the potency (<5-fold) or selectivity
      (<20-fold). The 3-(2,6-dichlorophenyl)-2-urea derivatives were slightly less
      active against VEGFR and less selective, being more effective against PDGFR (ca.
      10-fold) and c-Src (ca. 500-fold). The 3-(3,5-dimethoxyphenyl)-1,6-naphthyridines
      were generally more potent than the corresponding pyrido[2,3-d]pyrimidines
      against both VEGFR and FGFR (2- to 20-fold), with only slightly increased PDGFR
      and c-Src activity. The 3-(3,5-dimethoxyphenyl)-1,6-naphthyridine 2-ureas were
      also low nanomolar inhibitors of the growth of human umbilical vein endothelial
      cells (HUVECs) stimulated by serum, FGF, or VEGF, at concentrations that did not
      affect the growth of representative tumor cell lines, and were more (3- to 65
      fold) potent than the corresponding pyrido[2,3-d]pyrimidines.

PMID- 16000001
TI  - Potent androgen antagonists based on carborane as a hydrophobic core structure.
AB  - Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing
      polyhedral boron-cluster compounds having remarkable chemical and thermal
      stability and hydrophobic character. These features may allow application of
      carboranes as a new hydrophobic core structure in biologically active molecules
      that interact hydrophobically with receptors. We report here the design and
      synthesis of novel androgen antagonists bearing carborane. The most potent
      compounds, the arylcarborane derivatives 6e and 6i, exhibited antiandrogenic
      activity greater than that of the well-known antiandrogen hydroxyflutamide in
      reporter gene assay using NIH3T3 cells transfected with a human AR expression
      plasmid, as well as in cell growth inhibition assay using androgen-dependent SC-3
      cells. Further development of the potent carborane-containing androgen
      antagonists described here, having a new skeletal structure and unique
      characteristics, may yield novel therapeutic agents, especially selective
      androgen receptor modulators.

PMID- 16000002
TI  - The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines
      by aromatic iodination.
AB  - Aromatic iodination ortho to the phenolic hydroxyl reverts the activity of the
      ultrapotent vanilloid agonist resiniferatoxin (RTX, 1a), generating the
      ultrapotent antagonist 5'-iodoRTX (1b). To better understand the role of iodine
      in this remarkable switch of activity, a systematic investigation on the
      halogenation of vanillamides, a class of compounds structurally simpler than
      resiniferonoids, was carried out. The results showed that (a) the antagonistic
      activity depends on the site of halogenation and is maximal at C-6', (b) iodine
      is more efficient than chlorine and bromine at reverting the agonistic activity,
      and (c) iodine-carbon exchange decreases antagonist activity. Iodine-induced
      reversal of vanilloid activity was also observed in vanillamides more powerful
      than capsaicin, but a poor correlation was found between agonistic and
      antagonistic potencies, suggesting that differences exist in the way vanillamides
      and their 6'-iodo derivatives bind to TRPV1.' '

PMID- 16000003
TI  - Selective substrate-based inhibitors of mammalian dimethylarginine
      dimethylaminohydrolase.
AB  - The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide
      synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been
      synthesized, with optimization to give selective inhibition of DDAH with no
      significant direct effect on NOSs. These are the first examples of reversible
      DDAH inhibitors with significant activity and selectivity. In vivo administration
      increases plasma ADMA levels, giving proof of concept that these inhibitors can
      be used to probe the physiological effects of DDAH inhibition, with potential for
      pharmaceutical use of DDAH inhibitors in diseases where excess NO production is
      implicated.

PMID- 16000004
TI  - Second generation transition state analogue inhibitors of human 5'
      methylthioadenosine phosphorylase.
AB  - The polyamine biosynthetic pathway is a therapeutic target for proliferative
      diseases because cellular proliferation requires elevated levels of polyamines. A
      byproduct of the synthesis of spermidine and spermine is 5'-methylthioadenosine
      (MTA). In humans MTA is processed by 5'-methylthioadenosine phosphorylase (MTAP)
      so that significant amounts of MTA do not accumulate. Products of the MTAP
      reaction (adenine and 5-methylthio-alpha-D-ribose-1-phosphate) are recycled to S
      adenosylmethionine, the precursor for polyamine synthesis. Potent inhibitors of
      MTAP might allow the build-up of sufficient levels of MTA to generate feedback
      inhibition of polyamine biosynthesis and/or reduce S-adenosylmethionine levels.
      We recently reported the design and synthesis of a family of potent transition
      state analogue inhibitors of MTAP. We now report the synthesis of a second
      generation of stable transition state analogues with increased distance between
      the ribooxocarbenium ion and purine mimics. These compounds are potent inhibitors
      with equilibrium dissociation constants as low as 10 pM. The first and second
      generation inhibitors represent synthetic approaches to mimic early and late
      features of a dissociative transition state.

PMID- 16000005
TI  - Synthesis and biological evaluation of acyclic 3-[(2-hydroxyethoxy)methyl]
      analogues of antiviral furo- and pyrrolo[2,3-d]pyrimidine nucleosides.
AB  - The remarkably potent and specific activity against varicella-zoster virus (VZV)
      shown by 2'-deoxynucleosides of furo[2,3-d]pyrimidin-2(3H)-one and related ring
      systems is dependent on key structural features including the length and nature
      of the side-chain at C6 and the structure and stereochemistry of the sugar moiety
      at N3. Removal of the 3'-hydroxyl group from potent anti-VZV 2'-deoxynucleosides
      results in loss of the VZV activity, but such 2',3'-dideoxynucleoside analogues
      have shown anti-HCMV activity. We now report acyclic analogues with comparable
      side-chains at C6, but with the sugar moiety at N3 replaced with the (2
      hydroxyethoxy)methyl group (present in the antiherpes drug acyclovir). Examples
      of both furo[2,3-d]- and pyrrolo[2,3-d]pyrimidin-2(3H)-one acyclic analogues were
      prepared and evaluated in a number of virus-infected cells and in tumor cell
      cultures. Certain of the long-chain analogues showed activity against VZV and
      HCMV. No significant activity against other DNA and RNA virus replication or
      against tumor cell proliferation was observed.

PMID- 16000006
TI  - New pyrrolo[2,1-f]purine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives
      as potent and selective human A3 adenosine receptor antagonists.
AB  - Compounds presenting an additional fused ring on the xanthine nucleus have been
      reported to exhibit antagonistic activity with various levels of affinity and
      selectivity toward the four adenosine receptors subtypes A(1), A(2A), A(2B), and
      A(3). This paper reports synthesis and biological evaluation of new 1-benzyl-3
      propyl-1H,6H-pyrrolo[2,1-f]purine-2,4-diones and 1-benzyl-3-propyl-1H,8H
      imidazo[2,1-f]purine-2,4-diones, among which we identified potent and selective
      A(3) adenosine receptors antagonists. In particular, 1-benzyl-7-methyl-3-propyl
      1H,8H-imidazo[2,1-f]purine-2,4-dione (11e) shows a K(i) (hA(3)) value from
      binding assay of 0.8 nM.

PMID- 16000008
TI  - Spot detection and image segmentation in DNA microarray data.
AB  - Following the invention of microarrays in 1994, the development and applications
      of this technology have grown exponentially. The numerous applications of
      microarray technology include clinical diagnosis and treatment, drug design and
      discovery, tumour detection, and environmental health research. One of the key
      issues in the experimental approaches utilising microarrays is to extract
      quantitative information from the spots, which represent genes in a given
      experiment. For this process, the initial stages are important and they influence
      future steps in the analysis. Identifying the spots and separating the background
      from the foreground is a fundamental problem in DNA microarray data analysis. In
      this review, we present an overview of state-of-the-art methods for microarray
      image segmentation. We discuss the foundations of the circle-shaped approach,
      adaptive shape segmentation, histogram-based methods and the recently introduced
      clustering-based techniques. We analytically show that clustering-based
      techniques are equivalent to the one-dimensional, standard k-means clustering
      algorithm that utilises the Euclidean distance.

PMID- 16000009
TI  - A structured interface to the object-oriented genomics unified schema for XML
      formatted data.
AB  - Data management systems are fast becoming required components in many biology
      laboratories as the role of computer-based information grows. Although the need
      for data management systems is on the rise, their inherent complexities can deter
      the full and routine use of their computational capabilities. The significant
      undertaking to implement a capable production system can be reduced in part by
      adapting an established data management system. In such a way, we are leveraging
      the Genomics Unified Schema (GUS) developed at the Computational Biology and
      Informatics Laboratory at the University of Pennsylvania as a foundation for
      managing and analysing DNA sequence data in centromere research projects around
      Arabidopsis thaliana and related species. Because GUS provides a core schema that
      includes support for genome sequences, mRNA and its expression, and annotated
      chromosomes, it is ideal for synthesising a variety of parameters to analyse
      these repetitive and highly dynamic portions of the genome. Despite this,
      production-strength data management frameworks are complex, requiring dedicated
      efforts to adapt and maintain. The work reported in this article addresses one
      component of such an effort, namely the pivotal task of marshalling data from
      various sources into GUS. In order to harness GUS for our project, and motivated
      by efficiency needs, we developed a structured framework for transferring data
      into GUS from outside sources. This technology is embodied in a GUS object-layer
      processor, XMLGUS. XMLGUS facilitates incorporating data into GUS by (i)
      formulating an XML interface that includes relational database key constraint
      definitions, (ii) regularising traversal through that XML, (iii) realising
      automatic processing of the XML with database key constraints and (iv) allowing
      for special processing of input data within the framework for automated
      processing. The application of XMLGUS to production pipeline processing for a
      sequencing project and inputting the Arabidopsis genome into GUS is discussed.
      XMLGUS is available from the Flora website (http://flora.ittc.ku.edu/).

PMID- 16000010
TI  - An update on the functional molecular immunology (FIMM) database.
AB  - Data on the major histocompatibility complex, T-cell epitopes, B-cell epitopes,
      antigens and diseases are heterogeneous and scattered among different databases
      and the literature. Since it has become increasingly difficult to obtain an
      integrated view of functional immune response components, we have developed and
      updated over several years the Functional molecular IMMunology (FIMM) database
      (http:// research.i2r.a-star.edu.sg/fimm/). FIMM contains integrated expert
      curated data on protein antigens, and on human immunological receptors that
      recognise and bind them in healthy or disease states. Interfaces with multiple,
      intuitive query options and query reports provide immunologists with prioritised
      information that aids data interpretation, vaccine target discovery and immune
      disease research.

PMID- 16000011
TI  - Replication, variation and normalisation in microarray experiments.
AB  - INTRODUCTION: Microarray experiments often have complex designs that include
      sample pooling, biological and technical replication, sample pairing and dye
      swapping. This article demonstrates how statistical modelling can illuminate
      issues in the design and analysis of microarray experiments, and this information
      can then be used to plan effective studies. METHODS: A very detailed statistical
      model for microarray data is introduced, to show the possible sources of
      variation that are present in even the simplest microarray experiments. Based on
      this model, the efficacy of common experimental designs, normalisation
      methodologies and analyses is determined. RESULTS: When the cost of the arrays is
      high compared with the cost of samples, sample pooling and spot replication are
      shown to be efficient variance reduction methods, whereas technical replication
      of whole arrays is demonstrated to be very inefficient. Dye-swap designs can use
      biological replicates rather than technical replicates to improve efficiency and
      simplify analysis. When the cost of samples is high and technical variation is a
      major portion of the error, technical replication can be cost effective.
      Normalisation by centreing on a small number of spots may reduce array effects,
      but can introduce considerable variation in the results. Centreing using the bulk
      of spots on the array is less variable. Similarly, normalisation methods based on
      regression methods can introduce variability. Except for normalisation methods
      based on spiking controls, all normalisation requires that most genes do not
      differentially express. Methods based on spatial location and/or intensity also
      require that the nondifferentially expressing genes are at random with respect to
      location and intensity. Spotting designs should be carefully done so that spot
      replicates are widely spaced on the array, and genes with similar expression
      patterns are not clustered. DISCUSSION: The tools for statistical design of
      experiments can be applied to microarray experiments to improve both efficiency
      and validity of the studies. Given the high cost of microarray experiments, the
      benefits of statistical input prior to running the experiment cannot be over
      emphasised.

PMID- 16000012
TI  - Application of string kernels in protein sequence classification.
AB  - INTRODUCTION: The production of biological information has become much greater
      than its consumption. The key issue now is how to organise and manage the huge
      amount of novel information to facilitate access to this useful and important
      biological information. One core problem in classifying biological information is
      the annotation of new protein sequences with structural and functional features.
      METHOD: This article introduces the application of string kernels in classifying
      protein sequences into homogeneous families. A string kernel approach used in
      conjunction with support vector machines has been shown to achieve good
      performance in text categorisation tasks. We evaluated and analysed the
      performance of this approach, and we present experimental results on three
      selected families from the SCOP (Structural Classification of Proteins) database.
      We then compared the overall performance of this method with the existing protein
      classification methods on benchmark SCOP datasets. RESULTS: According to the F1
      performance measure and the rate of false positive (RFP) measure, the string
      kernel method performs well in classifying protein sequences. The method
      outperformed all the generative-based methods and is comparable with the SVM
      Fisher method. DISCUSSION: Although the string kernel approach makes no use of
      prior biological knowledge, it still captures sufficient biological information
      to enable it to outperform some of the state-of-the-art methods.

PMID- 16000013
TI  - Predicting RNA structure using mutual information.
AB  - BACKGROUND: With the ever-increasing number of sequenced RNAs and the
      establishment of new RNA databases, such as the Comparative RNA Web Site and
      Rfam, there is a growing need for accurately and automatically predicting RNA
      structures from multiple alignments. Since RNA secondary structure is often
      conserved in evolution, the well known, but underused, mutual information measure
      for identifying covarying sites in an alignment can be useful for identifying
      structural elements. This article presents MIfold, a MATLAB toolbox that employs
      mutual information, or a related covariation measure, to display and predict
      conserved RNA secondary structure (including pseudoknots) from an alignment.
      RESULTS: We show that MIfold can be used to predict simple pseudoknots, and that
      the performance can be adjusted to make it either more sensitive or more
      selective. We also demonstrate that the overall performance of MIfold improves
      with the number of aligned sequences for certain types of RNA sequences. In
      addition, we show that, for these sequences, MIfold is more sensitive but less
      selective than the related RNAalifold structure prediction program and is
      comparable with the COVE structure prediction package. CONCLUSION: MIfold
      provides a useful supplementary tool to programs such as RNA Structure Logo,
      RNAalifold and COVE, and should be useful for automatically generating structural
      predictions for databases such as Rfam.

PMID- 16000014
TI  - wolfPAC: building a high-performance distributed computing network for
      phylogenetic analysis using 'obsolete' computational resources.
AB  - wolfPAC is an AppleScript-based software package that facilitates the use of
      numerous, remotely located Macintosh computers to perform computationally
      intensive phylogenetic analyses using the popular application PAUP* (Phylogenetic
      Analysis Using Parsimony). It has been designed to utilise readily available,
      inexpensive processors and to encourage sharing of computational resources within
      the worldwide phylogenetics community.

PMID- 16000015
TI  - SeqState: primer design and sequence statistics for phylogenetic DNA datasets.
AB  - Choosing and designing primers based on available DNA sequence data and
      statistical contrasting of domains or structural features is a common routine
      among molecular biologists. Currently available, free software tools were found
      to lack desirable features related to these tasks. This was the motivation for
      developing a new program, SeqState. SeqState locates regions that remain to be
      sequenced in phylogenetic DNA datasets, evaluates user-provided primers and
      selects primers best suited to fill gaps in the sequences. If the primers
      provided by the user are unsuitable, new primers are designed. Primers can be
      loaded from a primer database, be supplied as part of the alignment or be entered
      manually. The position of internal primers is automatically localised in the
      loaded data file. Primers can be edited, and changes and new primers can be saved
      to the database. Primer sheets allow the user to view internal dimers,
      complements to a second primer, mismatches to all loaded sequences, and other
      primer characteristics. Calculation of various sequence statistics can be
      requested for the whole dataset or parts thereof (character sets), with standard
      errors estimated by bootstrapping. Insertion-deletion events can be evaluated
      statistically and encoded for subsequent phylogenetic analysis according to
      several published coding principles.

PMID- 16000016
TI  - BioLayout(Java): versatile network visualisation of structural and functional
      relationships.
AB  - Visualisation of biological networks is becoming a common task for the analysis
      of high-throughput data. These networks correspond to a wide variety of
      biological relationships, such as sequence similarity, metabolic pathways, gene
      regulatory cascades and protein interactions. We present a general approach for
      the representation and analysis of networks of variable type, size and
      complexity. The application is based on the original BioLayout program (C
      language implementation of the Fruchterman-Rheingold layout algorithm), entirely
      re-written in Java to guarantee portability across platforms. BioLayout(Java)
      provides broader functionality, various analysis techniques, extensions for
      better visualisation and a new user interface. Examples of analysis of biological
      networks using BioLayout(Java) are presented.

PMID- 16000017
TI  - Protecting science from abuse requires a broader form of outreach.

PMID- 16000018
TI  - Calories do not explain extension of life span by dietary restriction in
      Drosophila.
AB  - Dietary restriction (DR) extends life span in diverse organisms, including
      mammals, and common mechanisms may be at work. DR is often known as calorie
      restriction, because it has been suggested that reduction of calories, rather
      than of particular nutrients in the diet, mediates extension of life span in
      rodents. We here demonstrate that extension of life span by DR in Drosophila is
      not attributable to the reduction in calorie intake. Reduction of either dietary
      yeast or sugar can reduce mortality and extend life span, but by an amount that
      is unrelated to the calorie content of the food, and with yeast having a much
      greater effect per calorie than does sugar. Calorie intake is therefore not the
      key factor in the reduction of mortality rate by DR in this species.

PMID- 16000019
TI  - The evolution of connectivity in metabolic networks.
AB  - Processes in living cells are the result of interactions between biochemical
      compounds in highly complex biochemical networks. It is a major challenge in
      biology to understand causes and consequences of the specific design of these
      networks. A characteristic design feature of metabolic networks is the presence
      of hub metabolites such as ATP or NADH that are involved in a high number of
      reactions. To study the emergence of hub metabolites, we implemented computer
      simulations of a widely accepted scenario for the evolution of metabolic
      networks. Our simulations indicate that metabolic networks with a large number of
      highly specialized enzymes may evolve from a few multifunctional enzymes. During
      this process, enzymes duplicate and specialize, leading to a loss of biochemical
      reactions and intermediary metabolites. Complex features of metabolic networks
      such as the presence of hubs may result from selection of growth rate if
      essential biochemical mechanisms are considered. Specifically, our simulations
      indicate that group transfer reactions are essential for the emergence of hubs.

PMID- 16000020
TI  - Follow the money--the politics of embryonic stem cell research.

PMID- 16000021
TI  - Evolution at two levels: on genes and form.

PMID- 16000022
TI  - School students as Drosophila experimenters.

PMID- 16000023
TI  - After 30 years of study, the bacterial SOS response still surprises us.

PMID- 16000025
TI  - "I'd rather watch TV": an examination of physical activity in adults with mental
      retardation.
AB  - Interpretive ethnography was used as a framework to examine perceptions of
      physical activity behavior of 12 adults with mild mental retardation. Four
      parents and two job supervisors also agreed to participate. Multiple data sources
      included in-depth interviews, diaries, accelerometry, and informal observations.
      Participants reported many physical activity barriers, benefits, and leisure
      choices similar to the general population; however, two particularly salient
      themes related to negative influences and lack of guidance from support systems
      were apparently unique to this group. Results suggest that (a) adults with mental
      retardation need specially designed physical activity education and training
      programs and (b) supports system providers should be educated regarding the
      importance of physical activity to health for these individuals.

PMID- 16000024
TI  - Five futures for academic medicine.

PMID- 16000026
TI  - Family experiences associated with a child's diagnosis of fragile X or Down
      syndrome: evidence for disruption and resilience.
AB  - Although previous findings have shown that parents react intensely to the initial
      diagnosis of their child's disability, studies focused on long-term outcomes and
      adjustment are needed. We interviewed 21 mothers whose adolescent or young adult
      was diagnosed with Down syndrome or fragile X syndrome. Qualitative analysis of
      data focused on the diagnostic process and the child's development revealed
      emergent themes: importance of context, variations in emotional reactions to the
      diagnosis, use of specific coping strategies, and changes in family adaptation
      over time. Results indicate most families experienced elements of disruption and
      resilience in their reactions to the diagnosis, although different patterns
      emerged for each syndrome group. Maternal descriptions highlighted positive
      attributes that contributed to family well-being and behavioral challenges that
      were a source of family stress.

PMID- 16000027
TI  - Visual indictment: a contextual analysis of the Kallikak Family photographs.
AB  - The Kallikak Family is a pre-eminent text in the history of mental retardation
      and psychology in which Goddard (1912) claimed he proved the heritability of
      feeble-mindedness and the necessity of institutionalization. The book contains 14
      photographs, some of which have been retouched. These photographs were
      interpreted in this paper within the context of clinical photography of the
      feeble-minded during the eugenics era, and the conclusion was made that the
      photographs are masterpieces of visual indictment propaganda that worked on the
      levels of assumed scientific objectivity, hovel imagery, mutually amplifying
      juxtapositions, stereotypic images of imbecility, and religious symbolism to
      achieve persuasiveness. A resolution of alleged "skullduggery" surrounding the
      retouching is presented.

PMID- 16000028
TI  - Quality of life dimensions for adults with developmental disabilities: a
      comparative study.
AB  - The quality of life construct has gained prominent attention in human services
      over the last 20 years. We investigated whether quality of life differences exist
      between adults with developmental disabilities and the general population.
      Differences were found in scales measuring well-being and decision-making as well
      as other more specific variables. The two groups also differed in overall quality
      of life; those with developmental disabilities had lower quality of life. A
      logistic regression model comprised of the life dimensions differentiated between
      the groups with over 90% accuracy. Overall results of this static group
      comparison indicate that adults with developmental disabilities are at a
      significant disadvantage with regard to quality of life in comparison with the
      general population.

PMID- 16000029
TI  - First, do no harm--an argument against mandatory high-stakes testing for students
      with intellectual disabilities.

PMID- 16000030
TI  - Own home and host family options growing rapidly as more than 70% of residential
      service recipients with ID/DD in 2004 live in settings of 6 or fewer.

PMID- 16000033
TI  - Encuentros Latinoamericanos de Fotoquimica y Fotobiologia (ELAFOT): the Latin
      American Photochemical and Photobiological Community.
AB  - The photochemical and photobiological researchers in Latin American meet
      biannually at a regional meeting known as Encuentros Latinoamericanos de
      Fotoquimica y Fotobiologia (ELAFOT). The goals of this series of meetings are to
      discuss leading scientific work, to become acquainted with the latest research
      findings in the discipline, to exchange ideas, to initiate collaborations between
      groups and to strengthen the scientific interactions between young researchers
      and senior experts from the region and from developed countries. During 8-12
      November 2004, the eighth such meeting took place in La Plata, Argentina. In this
      introduction we present a brief history of the ELAFOT meetings and a summary of
      the most recent gathering and the papers presented in this Symposium-in-Print.

PMID- 16000039
TI  - Highlights and Happenings.

PMID- 16000040
TI  - Billions for biodefense: federal agency biodefense budgeting, FY2005-FY2006.
AB  - Since 2001, the United States government has spent substantial resources on
      preparing the nation against a bioterrorist attack. An earlier article analyzed
      the civilian biodefense funding by the federal government from fiscal years 2001
      through 2005. This article updates those figures with budgeted amounts for fiscal
      year 2006, specifically analyzing the budgets and allocations for biodefense at
      the Department of Health and Human Services, the Department of Homeland Security,
      the Department of Agriculture, the Environmental Protection Agency, the National
      Science Foundation, and the Department of State.

PMID- 16000041
TI  - Anthrax countermeasures: current status and future needs.
AB  - The U.S. government does not yet have the range of medical countermeasures needed
      to protect its citizens from anthrax and other potential bioweapons. In the event
      of an anthrax attack, treatment interventions in addition to antibiotics would be
      needed so that very ill patients can be treated and clean-up crews can be better
      protected, especially if an engineered strain is used. This article describes
      specific anthrax countermeasures that are in development, barriers to
      development, and potential mechanisms the government could use to accelerate the
      movement of these countermeasures through the pipeline. A key challenge will be
      to encourage the transition of promising leads from basic research to the product
      development stage, when they may qualify for BioShield funds.

PMID- 16000042
TI  - Lessons learned from a regional strategy for resource allocation.
AB  - Two qualitative case studies focus on the allocation of CDC funds distributed
      during 2002 for bioterrorism preparedness in two Texas public health regions
      (each as populous and complex as many states). Lessons learned are presented for
      public health officials and others who work to build essential public health
      services and security for our nation. The first lesson is that personal
      relationships are the cornerstone of preparedness. A major lesson is that a
      regional strategy to manage funds may be more effective than allocating funds on
      a per capita basis. One regional director required every local department to
      complete a strategic plan as a basis for proportional allocation of the funds.
      Control of communicable diseases was a central component of the planning. Some
      funds were kept at the regional level to provide epidemiology services, computer
      software, equipment, and training for the entire region. Confirmation of the
      value of this regional strategy was expressed by local public health and
      emergency management officials in a focus group 1 year after the strategy had
      been implemented. The group members also pointed out the need to streamline the
      planning process, provide up-to-date computer networks, and receive more than
      minimal communication. This regional strategy can be viewed from the perspective
      of adaptive leadership, defined as activities to bring about constructive change,
      which also can be used to analyze other difficult areas of preparedness.

PMID- 16000043
TI  - Remediation of Bacillus anthracis contamination in the U.S. Department of Justice
      mail facility.
AB  - The U.S. Department of Justice (DOJ) mail facility in Landover, Maryland, was
      contaminated with Bacillus anthracis spores as a result of the 2001 anthrax
      bioterrorism attacks through the U.S. postal system. Surface environmental
      sampling within the facility indicated that the contamination was due to receipt
      of mail that had come in contact with Bacillus anthracis spores from the source
      letters at the Brentwood postal facility in Washington, DC. The DOJ adopted a two
      pronged approach for remediating the facility, using aqueous chlorine dioxide to
      decontaminate hard, nonporous surfaces and paraformaldehyde to fumigate two
      pieces of mail equipment. Before the start of the remediation activities, all
      porous materials were removed from the mail area. Since all postremediation
      environmental samples were negative for growth of Bacillus anthracis spores, the
      remediation was judged to be effective. The facility remained closed for almost
      4(1/2) months. The cleanup activities took about 2(1/2) months, with source
      reduction activities being the most time-consuming. Of the seven facilities that
      performed fumigations to remediate Bacillus anthracis contamination, the DOJ mail
      facility was the second building to be reopened.

PMID- 16000044
TI  - E3LSI research: an essential element of biodefense.
AB  - The threat of bioterrorism has prompted the U.S. to undertake a vast biodefense
      initiative, including funding biodefense-related scientific research at
      unprecedented levels. Unfortunately, the many ethical, economic, environmental,
      legal, and social implications (E(3)LSI) of biodefense research and activities
      are not yet receiving the attention they warrant. Previously, in laudable
      demonstrations of foresight and responsibility, the federal government has funded
      research into the E(3)LSI of other recent scientific endeavors--namely, the Human
      Genome Project and the nanotechnology research program--through directed
      appropriations from their respective research budgets. This article advocates and
      proposes a model for a portion of biodefense funding to be similarly set aside
      for an E(3)LSI research program to complement biodefense research, to ensure that
      bioterror preparedness does not give rise to harmful or otherwise undesirable
      unintended consequences.

PMID- 16000045
TI  - Confidence in crisis? Understanding trust in government and public attitudes
      toward mandatory state health powers.
AB  - In response to the possibility of a bioterror attack using smallpox, many states
      have updated and revised their current public health laws in line with the Model
      Act, which would effectively give states the right to invoke mandatory state
      health powers, such as quarantine or vaccine. Previous studies have supported the
      importance of allying with the public in creating and implementing effective
      bioterror response policies. Historical case studies and recent research suggest
      that when the public is not supportive of government health policies, they may be
      less willing to comply. In this study we analyze a recent survey to determine the
      effects of a set of variables, including aspects of trust in government that have
      been found in previous studies to influence public opposition to compulsory
      government health policies, on opinions about compulsory vaccination and
      quarantine.

PMID- 16000046
TI  - Protecting corporate america from bioterrorism and epidemics after the sunset of
      the terrorism risk insurance act.

PMID- 16000047
TI  - Preventing post-traumatic stress disorder after mass exposure to violence.
AB  - Bioterrorism preparedness plans must take into account the psychosocial
      consequences of exposure to mass violence. If possible, post-traumatic stress
      disorder (PTSD), which is associated with significant morbidity and cost, should
      be prevented. There are, however, no effective interventions that have been
      scaled up to prevent PTSD following mass exposure to violence. In fact,
      randomized controlled trials of the most commonly used preventive intervention,
      psychological debriefing, suggest no efficacy, or even potential harm.
      Fortunately, randomized controlled trials of cognitive behavioral therapy--that
      is, targeting individuals who are symptomatic in the weeks after trauma--reveal
      significant efficacy. Given the potential for repeated mass violence exposure,
      public health professionals need to refine methods for screening and tracking
      large numbers of casualties. At the same time, the use of telephone and internet
      based cognitive behavioral therapy protocols should be further tested as
      strategies for bringing the only effective early intervention for PTSD to scale.
      Research on preventive pharmacotherapy for PTSD and on the effects of media
      exposure on PTSD severity is also a priority.

PMID- 16000049
TI  - Implementing UN Security Council Resolution 1540 to combat the proliferation of
      biological weapons.

PMID- 16000048
TI  - Beyond post-traumatic stress disorder.

PMID- 16000053
TI  - The innate reaction of the human skin lymphatic system to foreign and self
      antigens.
AB  - The skin lymphatic system is the constitutive anatomical organization of the
      innate immune system. It reacts immediately to penetrating foreign antigens and
      presents them to the organized lymphoid tissue, where subsequently the adaptive
      immune response develops. Both phylogenetically and ontogenetically, defense
      mechanisms ascribed to the lymphatic system developed earlier than the nutritive
      function of blood elements. Resident and migrating immune cells, regulatory
      proteins, neuroregulatory factors, complement components, coagulation factors,
      and antimicrobial peptides react immediately to foreign antigens. Moreover, they
      most likely participate in elimination of shed autoantigens. Thus far, the
      knowledge of specific events and mechanisms operative in the innate response is
      still in a premordial stage. Further studies will elucidate not only how we
      immediately recognize what is nonself and react to it but also learn more about
      evolution of local immune memory in the immune and parenchymatous cells.

PMID- 16000054
TI  - Pediatric admissions and procedures for lymphatic malformations in the United
      States: 1997 and 2000.
AB  - OBJECTIVE: To describe the incidence of discharges for lymphatic malformation
      (LM) and the various treatments rendered for this condition in a nationwide
      sampling of pediatric discharges from 1997 and 2000. DATA SOURCE: The 1997 and
      2000 Kid's Inpatient Database (KID), available through the Agency for Healthcare
      Research and Quality (AHRQ). DATA EXTRACTION: The sampling scheme of this
      database allowed for calculation of national and regional estimates using STATA
      8.2. DATA SYNTHESIS: There were an estimated 3200 admissions for the treatment of
      pediatric LM in 1997 and 2000 combined. These admissions were most common in
      urban teaching institutions (69% in 1997 and 81% in 2000). The mean age at
      admission was 3.7 years, while the median was 1 year. The most common procedure
      performed in these children was surgical excision of the malformation. Over half
      of these were done in children under age 2. Airway endoscopy was the second most
      common procedure. Sclerotherapy was infrequently performed. The estimated
      national hospital charges for these admissions were $26 million in 1997 and $35
      million in 2000. CONCLUSIONS: This analysis reveals a national perspective on the
      total number of pediatric admissions for LM and their associated inpatient
      procedures. Treatment trends for pediatric LM have remained relatively stable
      between 1997 and 2000, but hospital charges have increased.

PMID- 16000055
TI  - Tissue tonometry before and after liposuction of arm lymphedema following breast
      cancer.
AB  - BACKGROUND: Arm lymphedema is a common complication after breast cancer
      treatment. Different conservative and surgical treatments have been used to
      reduce the arm swelling, but most have failed as chronic edema eventually
      transforms from a state of accumulated lymph fluid into increased deposition of
      subcutaneous fat, i.e. a non-pitting lymphedema. OBJECTIVE: To evaluate changes
      in tissue tonicity with an electronic tissue tonometer before and after
      liposuction. To validate the tonometer, outcome of surgery, and aspirate content.
      If tonometry can discriminate between "soft" and "hard" edema/swelling, it can be
      used to differentiate these types, as treatment differs. SUBJECTS AND METHODS:
      Twenty women with non-pitting unilateral postmastectomy arm lymphedema were
      operated on. The following measurements were performed: Tissue tonicity with a
      tonometer, its sensitivity on five different foam-polyethers by ten subjects, arm
      volumes, and adipose tissue aspirate content. RESULTS: Tissue tonicity values
      showed that the upper lymphedematous arm was harder than the normal one. After
      surgery it became softer, and at one year it was as soft as the normal arm.
      Polyether tonometries could clearly differentiate the various properties. A
      sample of three measurements was as good as ten. Horizontal vs. vertical
      measurements did not differ in the high-density polyethers. Complete reduction of
      the lymphedema was achieved. Adipose tissue content of the aspirate was 89%.
      CONCLUSION: The tonometer could register postoperative changes in tissue tonicity
      in the upper arm, but not in the forearm, which also showed significantly higher
      absolute values. Probably this is caused by the high adipose tissue content with
      little or no free fluid, thus resembling the normal arm in tonicity. Possibly
      also the thinner subcutaneous tissue in the forearm plays a role. Tonometry can
      differentiate if a lymphedematous arm that is softer or harder than the normal
      one. A harder swelling is dominated by adipose tissue and can be treated with
      liposuction, while the softer one is treated conservatively.

PMID- 16000056
TI  - Pharmacogenomics: its role in re-establishing coumarin as treatment for
      lymphedema.
AB  - Although there remains some significant controversy regarding the use and
      benefits of coumarin (5,6-benzo-alpha pyrone), it would seem that targeted
      appropriate and monitored use of the drug does have a significant role in the
      treatment of lymphedemas. The particular benefits are its cost and ease of
      administration. Given today's demands for high level investigative clinical
      trials, it would be virtually impossible to conduct a study large enough to make
      any significant conclusions about hepatotoxic effects. However, it seems without
      doubt that the majority of studies conducted thus far suggest that coumarin (and
      other benzopyrones, i.e., the ruto-sides, which do not have hepatotoxic effects
      and which are often discussed in aggregate with coumarin) is effective in
      treating lymphedema, particularly when used in conjunction with complex physical
      therapy. The use of pharmacogenomics could significantly lower the risk of
      coumarin-associated hepatotoxicity, by targeting the use of coumarin to those
      with functional CYP2A6. Further research in this area will be required to re
      evaluate the cost- benefit ratio and to determine the potential for the
      reintroduction of coumarin as a potent treatment for lymphedema. The perceived
      negative image of coumarin should not be allowed to carry across to the other
      benzopyrones, as they still confer a significant benefit in the management of
      lymphedemas.

PMID- 16000057
TI  - Literature watch. Complete and specific inhibition of adult lymphatic
      regeneration by a novel VEGFR-3 neutralizing antibody.

PMID- 16000060
TI  - Recombinant adeno-associated viral vectors in the nervous system.
AB  - Recombinant adeno-associated virus 2 (rAAV2) has been extensively used as a gene
      delivery vector for the nervous system. It targets primarily neurons in the
      nervous system and results in sustained long-term expression of transgenes. New
      rAAV serotypes have been characterized and demonstrated to have improved
      transduction efficiencies in various regions of the brain and spinal cord. This
      review discusses some properties of rAAV that have been studied in the nervous
      system such as cell tropism, duration of transgene expression, and distribution
      of viral transduction, as well as immunity and regulation of transgene expression
      issues, all of which are important for optimization of the use of rAAV in the
      nervous system.

PMID- 16000061
TI  - Hematopoietic stem cell transduction by recombinant adeno-associated virus
      vectors: problems and solutions.
AB  - Recombinant adeno-associated virus 2 (AAV) vectors have taken center stage owing
      to their potentially safer profile compared with the more commonly used
      retroviral and adenoviral vectors in human gene therapy clinical trials. Their
      remarkable versatility and efficacy in a wide variety of preclinical animal
      models of human diseases have attracted further attention of a number of
      investigators. Although two particular cell types, muscle and brain, have been
      shown to be highly transducible by AAV vectors, controversies abound with
      reference to the efficacy of these vectors in transducing primary hematopoietic
      cells. Whereas some investigators have claimed that primitive hematopoietic cells
      are impervious to AAV vectors, others have reported that AAV vectors are capable
      of transducing these cells, but only at high vector-to-cell ratios. Still other
      investigators have reported successful transduction of primitive hematopoietic
      cells at relatively low vector-to-cell ratios. This review attempts to resolve
      these controversies, and provides a basis for the optimism that safe and high
      efficiency transduction of hematopoietic stem and progenitor cells by AAV vectors
      is well within reach.

PMID- 16000062
TI  - Redirecting human T lymphocytes toward renal cell carcinoma specificity by
      retroviral transfer of T cell receptor genes.
AB  - Adoptive T cell therapy of renal cell carcinoma (RCC) is limited by the
      difficulty in generating sufficient numbers of RCC-reactive T cells in vitro. To
      circumvent this problem, we cloned T cell receptor (TCR) alpha and beta chains
      from a tumor-infiltrating lymphocyte clone specific for an RCC tumor antigen and
      transferred the TCR into human T cell lines and primary T lymphocytes. Efficient
      TCR expression in primary T lymphocytes was obtained only with a mouse
      myeloproliferative sarcoma virus (MPSV)-based retroviral vector, not with a
      Moloney murine leukemia virus (MLV)-based vector, although both viral
      supernatants were similar in titer, as shown by analysis of copy number
      integration in transduced T cells. Reverse transcription-polymerase chain
      reaction analysis revealed a higher amount of TCR-encoding transcripts when T
      cells were transduced with the MPSV vector in comparison with the MLV vector,
      indicating that high TCR expression levels can be achieved by appropriate cis
      regulatory vector elements. The biological activity of the transferred TCR was
      shown by specific lysis of RCC cells ((51)Cr release assay) and by interferon
      gamma and tumor necrosis factor alpha release (enzyme-linked immunosorbent assay)
      in an antigen-specific and HLA-A*0201-restricted fashion. Comparison of the
      redirected T lymphocytes with the original tumor-infiltrating lymphocyte clone
      revealed similar killing and cytokine secretion capabilities. The functional
      activity of TCR-redirected T lymphocytes was stable over time. The results
      demonstrate that use of an optimized retroviral vector yielded a high TCR
      transduction efficiency and stable and high TCR expression in primary human T
      lymphocytes and redirected their specificity toward RCC cells.

PMID- 16000063
TI  - Sustained phenotypic correction of canine hemophilia B after systemic
      administration of helper-dependent adenoviral vector.
AB  - We have evaluated the potential of liver-directed, helper-dependent adenoviral
      (HDAd) vector-mediated gene therapy in the hemophilia B dog. Two dogs were
      injected intravenously with HDAd (3 x 10(12) VP/kg) bearing a liver-restricted
      canine coagulation factor IX (FIX) expression cassette. After injection, the
      whole blood clotting time for both dogs declined from >60 min to </=20 min for at
      least 604 and 446 days, respectively. Peak FIX activities of 34.1 and 129.2% were
      detected at 12x14 days and then slowly declined to 2 to 5% by 120 days and
      stabilized at these therapeutic levels for at least 418 and 257 days. For one
      dog, a peak FIX level of 500 ng/ml was achieved and stabilized at >170 ng/ml for
      at least 256 days. For the other dog, a peak FIX level of 1258 ng/ml was achieved
      and stabilized at >400 ng/ml for at least 213 days. Inhibitor formation was not
      evident in either animal. Importantly, whereas untreated hemophilia B dogs suffer
      five or six spontaneous bleeds per year, the treated dogs suffered no such bleeds
      postinjection. Significantly, this study is the first to demonstrate long-term
      phenotypic correction of a genetic disorder in a large animal with HDAd. Although
      no evidence of chronic toxicity was observed in either animal, systemic vector
      administration at 3 x 10(12) VP/kg was accompanied by acute, albeit transient and
      variable laboratory abnormalities (alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, creatine phosphokinase, and platelet
      counts). The results of this study highlight both the potential benefit and the
      risk associated with systemic intravascular delivery of high-dose HDAd for liver
      directed gene therapy.

PMID- 16000064
TI  - Nonionic amphiphilic block copolymers promote gene transfer to the lung.
AB  - Various pulmonary disorders, including cystic fibrosis, are potentially amenable
      to a treatment modality in which a therapeutic gene is directly delivered to the
      lung. Current gene delivery systems, either viral or nonviral, need further
      improvement in terms of efficiency and safety. We reported that nonionic
      amphiphilic block copolymers hold promise as nonviral gene delivery systems for
      transfection of muscular tissues. To evaluate the efficiency of these vectors in
      the lung, intratracheal instillation or aerosolization of reporter genes
      complexed with Lutrol or PE6400 was performed. Lutrol-DNA and, to a lesser
      extent, PE6400-DNA complexes promoted efficient gene transfection into mouse
      airways in a dose-dependent manner. This improvement over naked DNA was observed
      irrespective of the reporter gene. Lutrol enabled us to deliver significantly
      higher DNA amounts than current nonviral vectors, with even greater increases in
      gene expression and without the formation of colloidally unstable complexes. Time
      course studies showed that Lutrol-DNA complexes permitted prolonged gene
      expression for up to 5 days whereas with poly(ethylenimine) (PEI)-DNA polyplexes,
      expression peaked on days 1-2 postinstillation, was strongly reduced by day 5,
      and reached background levels on day 7. Aerosolized delivery of Lutrol-DNA
      complexes, a less invasive approach to deliver genes to the lung, gave 5- to 15
      fold higher reporter gene expression compared with PEI-DNA polyplexes
      administered via the same delivery route. After intratracheal instillation of
      Lutrol-DNA complexes, histochemical staining for beta-galactosidase expression
      showed the presence of large blue areas. Histopathological analysis showed that
      Lutrol alone did not elicit inflammation, and that the inflammatory response
      after intratracheal instillation of Lutrol-DNA complexes was reversible and was
      observed only with the highest amounts of DNA. We also found that Lutrol can
      efficiently deliver genes to the airways of cystic fibrosis mice. Thus, we
      conclude that Lutrol is a highly promising vector for gene delivery to the lung.

PMID- 16000065
TI  - Tumor cell surface display of immunoglobulin heavy chain Fc by gene transfer as a
      means to mimic antibody therapy.
AB  - We hypothesized that inducing display of the immunoglobulin Fc (IgFc) molecule on
      the tumor cell surface by gene transfer would promote tumor cell killing by the
      same mechanisms as antibody-based approaches but would alleviate some of the
      problems inherent in the use of antibodies for cancer therapy. We expressed the
      cDNA of the Fc portion of the murine IgG2a heavy chain on the surface of tumor
      cells such that its C terminus projected away from the tumor cell surface,
      mimicking a natural antibody-tagging event. In vitro, Fc receptor-positive
      natural killer (NK) cells specifically recognized and lysed B16 melanoma cells
      expressing surface IgFc. Macrophages bound to B16-Fc cells significantly more
      than to parental B16 cells and surface IgFc expression promoted formation of the
      terminal complement pore complex leading to cell lysis and death. Expression of
      IgFc dramatically delayed the ability of B16 cells to form tumors in vivo,
      attributable largely to the effects of NK cells. Furthermore, fluorescence
      activated cell-sorting analysis showed that cells from outgrowth B16 IgFc tumors
      had lost all IgFc expression. When additional immunostimulatory signals were
      provided at the time of IgFc-mediated tumor cell killing through expression of
      heat shock protein 70 (hsp70), significant antitumor immunity was generated.
      Intratumoral delivery of an adenoviral vector expressing IgFc was effective at
      treating locally accessible tumors but did not impact metastatic disease.
      However, delivery of adenoviral vectors expressing both IgFc and hsp70 cured both
      local and metastatic tumors established for 6 days before viral treatment. These
      data suggest that it is possible to use gene transfer to mimic the beneficial
      properties of antibody therapy while alleviating some of the associated problems.

PMID- 16000066
TI  - Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for
      colorectal cancer.
AB  - It has been demonstrated that interleukin 24 (IL-24, also called melanoma
      differentiation associated gene 7) exerts antitumor activity. In this study, we
      investigated whether oncolytic adenovirus-mediated gene transfer of IL-24 could
      induce strong antitumor activity. A tumor-selective replicating adenovirus
      expressing IL-24 (ZD55-IL-24) was constructed by insertion of an IL-24 expression
      cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B
      55-kDa gene. ZD55-IL-24 could express substantially more IL-24 than Ad-IL-24
      because of replication of the vector. It has been shown that ZD55-IL-24 exerted a
      strong cytopathic effect and significant apoptosis in tumor cells with p53
      dysfunction. Moreover, no cytotoxic and apoptotic effects could be seen in normal
      cells infected with ZD55-IL-24. Expression of IL-24 did not interfere with viral
      replication induced by oncolytic adenovirus. Activation of caspase 3 and caspase
      9, and induction of bax gene expression, were involved in tumor cell apoptosis
      induced by ZD55-IL-24. Treatment of established tumors with ZD55-IL-24 showed
      much stronger antitumor activity than that induced by ONYX-015 or Ad-IL- 24.
      These data indicated that oncolytic adenovirus expressing IL-24 could exert
      potential antitumor activity and offer a novel approach to cancer therapy.

PMID- 16000067
TI  - Efficient inhibition of human telomerase reverse transcriptase expression by RNA
      interference sensitizes cancer cells to ionizing radiation and chemotherapy.
AB  - Telomerase activation plays critical roles in tumor growth and progression in
      part through the maintenance of telomere structure. Indeed, the ubiquitous
      expression of telomerase in human cancers makes telomerase a promising target for
      cancer therapy. Genetic, pharmacologic, and antisense methods to inhibit
      telomerase have been described; however, in most cases, cancer cell death was
      observed only after many cell divisions. Here, using retroviral delivery of small
      interfering RNAs (siRNAs) specific for the human telomerase reverse transcriptase
      (hTERT), we successfully inhibited telomerase activity in cervical cancer cell
      lines. Cells lacking hTERT expression exhibited significantly decreased
      telomerase activity and showed shortened telomeres and telomeric 3' overhangs
      with passage. These cells entered replicative senescence after a considerable
      number of cell divisions. Notably, the proliferative rate of these cells was
      significantly impaired, compared with control cells with telomerase activity,
      even in low-passage cells (population doubling 5). Likewise, colony-forming
      ability and tumorigenicity in mice were attenuated in low-passage cells lacking
      hTERT. We further examined the effects of chemotherapy and ionizing radiation on
      cells in which hTERT expression was suppressed. Cells lacking hTERT showed a
      significantly increased sensitivity, compared with control cells, to ionizing
      radiation or chemotherapeutic agents that induce DNA double- strand breaks, such
      as topoisomerase inhibitors or bleomycin. These findings suggest that an siRNA
      based strategy can be applied to the development of novel telomerase inhibitors,
      the antitumor effects of which may be enhanced in combination with ionizing
      radiation and chemotherapy.

PMID- 16000068
TI  - In vitro restoration of functional SMN protein in human trophoblast cells
      affected by spinal muscular atrophy by small fragment homologous replacement.
AB  - The majority of patients affected by spinal muscular atrophy (SMA) have deletion
      of the survival of motor neuron 1 (SMN1) gene, but they retain a "nonfunctional"
      copy of the duplicate gene (SMN2) in their genome. SMN2 produces defective SMN
      protein because of a C --> T transition in exon 7, which causes the skipping of
      exon 7 during SMN mRNA maturation. Many attempts have been made to correct
      altered SMN gene expression and to increase the level of normal SMN protein, but
      to date an effective treatment for this disease has not been established. Small
      Fragment Homologous Replacement (SFHR) is a site-specific gene modification
      approach that has the potential to maintain the genomic organization necessary
      for expression. The target modification in the genome is mediated by small DNA
      fragments (SDFs) 400-800 bp in length. In this study we used SFHR to induce a T -
      > C transition at codon 280 in exon 7 of the SMN2 gene in order to produce an
      increase in functional SMN protein. SDFs were transfected in vitro into cells
      obtained from five human fetal chorionic villi of embryos, homozygous for the
      SMN1 deletion, by either electroporation or microinjection. Transfected SMA cells
      showed an increase of up to 53% in full-length SMN mRNA compared with
      untransfected controls, as detected by real-time polymerase chain reaction.
      Consistent with the RNA data, immunocytochemistry and immunoblotting revealed a
      significant 2-fold increase in wild-type SMN protein. Furthermore, genotype and
      phenotype of transfected cells remained stable after several in vitro passages,
      demonstrating the stability of the correction over time.

PMID- 16000069
TI  - Diverse plasmid DNA vectors by directed molecular evolution of cytomegalovirus
      promoters.
AB  - Genetic vaccinations, gene therapy, and manufacturing of therapeutic proteins
      would benefit from promoter sequences that provide improved or prolonged
      expression levels. The cytomegalovirus (CMV) promoter is one of the most potent
      promoters known to date, and no previous examples of improved activity of this
      promoter by sequence mutagenesis have been reported. This study describes
      directed molecular evolution of CMV promoters derived from two human and two
      nonhuman primate strains of CMV by DNA shuffling and screening. Libraries of
      chimeric promoters were screened and analyzed for expression levels and immune
      responses, using plasmid DNA vectors encoding luciferase and beta-galactosidase.
      The results indicate that high functional diversity among CMV promoters can be
      generated, and the chimeric promoters selected after two rounds of DNA shuffling
      and particularly designed screening assays provided approximately 2-fold
      increased luciferase reporter gene expression and anti-beta-galactoside antibody
      response in vivo when compared with wild-type promoters. Sequence analysis of the
      shuffled promoters identified several mutations potentially contributing to the
      observed enhanced or reduced promoter activities and identified a 42-nucleotide
      region that appears obsolete for the functioning of the CMV promoter. Taken
      together, these data demonstrate the feasibility of generating diverse promoter
      sequences by DNA shuffling and screening methods, and provide novel structure-
      function information about CMV promoters. DNA shuffling and screening
      technologies provide a new approach to promoter optimization and development of
      optimal expression vectors for genetic vaccinations, gene therapy, and protein
      expression.

PMID- 16000070
TI  - Ultrasound enhances gene delivery of human factor IX plasmid.
AB  - Delivery of plasmid DNA can be enhanced by treatment with ultrasound (US);
      acoustic cavitation appears to play an important role in the process. Ultrasound
      contrast agents (UCAs; stabilized microbubbles) nucleate acoustic cavitation, and
      lower the acoustic pressure threshold for inertial cavitation occurrence. Fifty
      micrograms of a liver-specific, high-expressing human factor IX plasmid, pBS
      HCRHP-FIXIA, mixed with UCA or phosphate-buffered saline was delivered to mouse
      livers by intrahepatic injection, with simultaneous exposure to 1 MHz-pulsed US
      using various acoustic protocols. Variable pulse duration (PD) at constant
      treatment time, pulse repetition frequency, and an acoustic peak negative
      pressure amplitude of 1.8 MPa produced 2- to 13-fold enhancements in hFIX gene
      expression, but PD was not a strong determinant. In contrast, a dose-response
      relationship was demonstrated for the peak negative pressure (P-), with
      significant enhancement of gene transduction at P- >/= 2 MPa. Up to 63 ng/ml
      (approaching the therapeutic range for treating hemophilia patients) could be
      achieved by transducing one liver lobe at 4-MPa P-, corresponding to a 66- fold
      increment relative to treatment with naked DNA alone. Under the same conditions,
      mouse livers could also be transduced with a GFP plasmid. Histology showed
      transient liver damage caused by intrahepatic injection and US exposure at 4-MPa
      P-; however, the damage was repaired in a few days. We conclude that therapeutic
      US in combination with UCA has the potential to promote safe and efficient
      nonviral gene transfer of hFIX for the treatment of hemophilia.

PMID- 16000073
TI  - What have we learned from proteomic studies of serum?

PMID- 16000071
TI  - Posttranslational control of a cardiac ion channel transgene in vivo:
      clarithromycin-hMiRP1-Q9E interactions.
AB  - The present study investigates a novel gene therapy approach for atrial
      arrhythmias, using a clarithromycin-responsive ion channel subunit mutation,
      hMiRP1-Q9E, cloned into an expression plasmid; wild-type expression plasmids
      encoding human minK-related protein 1 (hMiRP1) were also used as controls. In a
      series of pig studies, right atrial myocardium was injected at one site with
      hMiRP1-Q9E plasmid DNA; a separate site in the same right atrium was injected
      with wild-type plasmid or was sham injected. Two weeks after transfection
      intravenous clarithromycin administration resulted in a site-specific, dose
      dependent prolongation of the repolarization phase of the right atrial epicardial
      monophasic action potential (MAP) only at the hMiRPQ9E sites, but not at sham or
      wild-type sites. MAP recordings before clarithromycin administration did not
      differ between hMiRP1-Q9E and control sites. These studies show that regional
      control of atrial myocardial repolarization by site-specific transfection with
      plasmid DNA encoding an antibiotic-responsive ion channel subunit is feasible
      and, because hMiRP1-Q9E-transfected sites were affected only if clarithromycin
      was given, provide proof of concept for a posttranslational, controllable gene
      therapy strategy for atrial arrhythmias.

PMID- 16000075
TI  - Second proteomics standards initiative spring workshop.

PMID- 16000076
TI  - Keystone symposia: proteomics and bioinformatics and systems and biology.

PMID- 16000077
TI  - Complex proteome prefractionation using microscale solution isoelectrofocusing.
AB  - The proteomes of mammalian cells, tissues and biologic fluids are complex and
      consist of proteins present over a wide dynamic range. Current protein profiling
      technologies do not have the capacity to overcome the sample complexity for
      comprehensive analysis of complex proteomes. A common strategy to substantially
      expand protein profiling capacities is sample prefractionation. A
      prefractionation method developed in the authors' laboratory, microscale solution
      isoelectrofocusing, has resulted in a commercial product, the ZOOM IEF
      Fractionator, which provides a simple and convenient method for high-resolution
      separation of complex proteomes based upon their isoelectric points. Complex
      human samples such as cancer cells and biologic fluids can be fractionated into
      well-resolved fractions with minimal cross-contamination of proteins between
      adjacent fractions. This review focuses on the application of microscale solution
      isoelectrofocusing prefractionation and subsequent downstream strategies in
      expanding protein profiling capacities and mining low-abundance proteins of
      complex proteomes.

PMID- 16000078
TI  - Manipulation of oxygen tensions for in vitro cell culture using a hypoxic
      workstation.
AB  - It is increasingly clear that oxygen tension exerts potent effects on many
      biologic processes in a range well above that at which aerobic metabolism is
      compromised. Cell culture ex vivo is traditionally performed in unstirred liquid
      media at ambient oxygen concentrations in the laboratory, with no attention to
      the level of oxygen experienced by the cells. This is certainly not reflecting
      physiology, and oxygenation may be further altered during cell handling and
      extraction procedures. The hypoxia-inducible factor pathway illustrates the
      potential for oxygen tension to have dramatic effects in terms of post
      translational modification of proteins, and to influence a broad range of
      cellular pathways including those involved in substrate transport, metabolic
      pathways, growth factor signaling and differentiation. While the standard
      laboratory approach may remain suitable for many biologic applications, there are
      other situations in which more attention to oxygenation will be appropriate. This
      review discusses a workstation that allows investigators to manipulate
      oxygenation.

PMID- 16000079
TI  - Population proteomics: addressing protein diversity in humans.
AB  - In the past several years, proteomics and its subdiscipline clinical proteomics
      have been engaged in the discovery of the next generation protein of biomarkers.
      As the effort and the intensive debate it has sparked continue, it is becoming
      apparent that a paradigm shift is needed in proteomics in order to truly
      comprehend the complexity of the human proteome and assess its subtle variations
      among individuals. This review introduces the concept of population proteomics as
      a future direction in proteomics research. Population proteomics is the study of
      protein diversity in human populations. High-throughput, top-down mass
      spectrometric approaches are employed to investigate, define and understand
      protein diversity and modulations across and within populations. Population
      proteomics is a discovery-oriented endeavor with a goal of establishing the
      incidence of protein structural variations and quantitative regulation of these
      modifications. Assessing human protein variations among and within populations is
      viewed as a paramount undertaking that can facilitate clinical proteomics' effort
      in discovery and validation of protein features that can be used as markers for
      early diagnosis of disease, monitoring of disease progression and assessment of
      therapy. This review outlines the growing need for analyzing individuals'
      proteomes and describes the approaches that are likely to be applied in such a
      population proteomics endeavor.

PMID- 16000080
TI  - Tissue microarrays: bridging the gap between research and the clinic.
AB  - Tissue microarrays are a high-throughput method for the investigation of
      biomarkers in multiple tissue specimens at once. This technique allows for the
      analysis of up to 500 tissue samples in a single experiment using
      immunohistochemistry and in situ hybridization. Recently, cell lines and
      xenografts have been reduced to a tissue microarray format and are being applied
      to preclinical drug development. In clinical research, tissue microarrays are
      applied at multiple levels: comprehensive analysis of samples in the context of a
      clinical trial or across a population. Tissue microarrays play a central role in
      translational research, facilitating the discovery of molecules that have
      potential roles in the diagnosis, prognosis and prediction of response to
      therapy.

PMID- 16000081
TI  - Morphoproteomics: exposing protein circuitries in tumors to identify potential
      therapeutic targets in cancer patients.
AB  - Morphoproteomics combines the disciplines of histopathology, molecular biology
      and protein chemistry to paint a portrait of the protein circuitry in diseased
      cells for the purpose of uncovering molecular targets amenable to specific
      intervention, thereby customizing therapy for individual patients. This review
      considers the clinical application of morphoproteomics in malignant cells in the
      context of currently available pharmaceutical agents and discusses opportunities
      for combinatorial approaches that involve one or more small molecule inhibitors
      and single-agent chemotherapy with relatively low toxicity profiles. Future
      directions that involve focusing on points of convergence in signal transduction
      pathways and which integrate morphoproteomic with genomic and pharmacoproteomic
      and protein-function microarray data are offered.

PMID- 16000082
TI  - Proteomic analysis of renal diseases: unraveling the pathophysiology and
      biomarker discovery.
AB  - Current biomedical applications of proteomics have been conducted with four main
      objectives: to better understand the normal biology and physiology of cells,
      microorganisms, tissues and organs; to explore the pathogenic mechanisms and
      better understand the pathophysiology of medical diseases; to identify novel
      biomarkers for early disease detection, prediction and prognosis; and to define
      new therapeutic targets, drugs and vaccines. This review focuses predominantly on
      proteomic applications to unravel the pathophysiology and to define novel
      biomarkers for various renal diseases (i.e., glomerular diseases,
      tubulointerstitial diseases, renal vascular disorders and renal cancers). In
      addition, proteomic evaluations of renal transplantation and renal replacement
      therapy (for acute renal failure and end-stage renal disease) are summarized.
      Personal opinion, future perspectives and information resources for the field of
      renal and urinary proteomics are provided.

PMID- 16000083
TI  - Use of proteomics to define targets of T-cell immunity.
AB  - The mammalian immune system has evolved to display peptides derived from
      microbial antigens to immune effector cells. Liberated from the intact antigens
      through distinct proteolytic mechanisms, these peptides are subsequently
      transported to the cell surface while bound to chaperone-like receptors known as
      major histocompatibility complex molecules. These complexes are then scrutinized
      by T-cells that express receptors with specificity for specific major
      histocompatibility complex-peptide complexes. In normal uninfected cells, this
      process of antigen processing and presentation occurs continuously, with the
      resultant array of self-antigen-derived peptides displayed on the surface of
      these cells. Changes in this cellular peptide array alert the immune system to
      changes in the intracellular environment that may be associated with infection,
      oncogenesis or other abnormal cellular processes, resulting in a cascade of
      events that result in the elimination of the abnormal cell. Since peptides play
      such an essential role in informing the immune system of infection with viral or
      microbial pathogens and the transformation of cells in malignancy, the tools of
      proteomics, in particular mass spectrometry, are ideally suited to study these
      immune responses at a molecular level. Recent advances in studies of immune
      responses that have utilized mass spectrometry and associated technologies are
      reviewed. The authors gaze into the future and look at current challenges and
      where proteomics will impact in immunology over the next 5 years.

PMID- 16000084
TI  - Mass spectrometry-based peptide quantification: applications and limitations.
AB  - In various areas of research, proteomics and particularly the quantification of
      proteins and peptides renders a useful addition to biochemical experiments. The
      range of possible applications varies from supervision of concentration changes
      of relevant proteins during biogenesis to differential proteomics approaches,
      distinguishing, for instance, healthy and diseased states. Furthermore, mass
      spectrometry-based peptide quantification yields the possibility of using highly
      sensitive bottom-up approaches for determination of protein regulations as well
      as multiplexing capability. Thereby, changes in protein abundances may be linked
      to specific cellular states bearing the opportunity to reveal marker proteins for
      several diseases.

PMID- 16000085
TI  - Rarity gives a charm: evaluation of trace proteins in plasma and serum.
AB  - Since plasma potentially contacts every cell as it circulates through the body,
      it may carry clues both to diagnosis and treatment of disease. It is commonly
      expected that the growing ability to detect and characterize trace proteins will
      result in discovery of novel therapeutics and biomarkers; however, the familiar,
      super-abundant plasma proteins remain a fundamental stumbling block. Furthermore,
      robust validation of proteomic data is a sometimes overlooked but always
      necessary component for the eventual development of clinical reagents. This
      review surveys some of the uses of typical and atypical low-abundance proteins,
      current analytical methods, existing impediments to discovery, and some
      innovations that are overcoming the challenges to evaluation of trace proteins in
      plasma and serum.

PMID- 16000086
TI  - High-throughput proteomics using matrix-assisted laser desorption/ ionization
      mass spectrometry.
AB  - It has become evident that the mystery of life will not be deciphered just by
      decoding its blueprint, the genetic code. In the life and biomedical sciences,
      research efforts are now shifting from pure gene analysis to the analysis of all
      biomolecules involved in the machinery of life. One area of these postgenomic
      research fields is proteomics. Although proteomics, which basically encompasses
      the analysis of proteins, is not a new concept, it is far from being a research
      field that can rely on routine and large-scale analyses. At the time the term
      proteomics was coined, a gold-rush mentality was created, promising vast and
      quick riches (i.e., solutions to the immensely complex questions of life and
      disease). Predictably, the reality has been quite different. The complexity of
      proteomes and the wide variations in the abundances and chemical properties of
      their constituents has rendered the use of systematic analytical approaches only
      partially successful, and biologically meaningful results have been slow to
      arrive. However, to learn more about how cells and, hence, life works, it is
      essential to understand the proteins and their complex interactions in their
      native environment. This is why proteomics will be an important part of the
      biomedical sciences for the foreseeable future. Therefore, any advances in
      providing the tools that make protein analysis a more routine and large-scale
      business, ideally using automated and rapid analytical procedures, are highly
      sought after. This review will provide some basics, thoughts and ideas on the
      exploitation of matrix-assisted laser desorption/ ionization in biological mass
      spectrometry - one of the most commonly used analytical tools in proteomics - for
      high-throughput analyses.

PMID- 16000087
TI  - Ribosome display: next-generation display technologies for production of
      antibodies in vitro.
AB  - Antibodies represent an important and growing class of biologic research reagents
      and biopharmaceutical products. They can be used as therapeutics in a variety of
      diseases. With the rapid expansion of proteomic studies and biomarker discovery,
      there is a need for the generation of highly specific binding reagents to study
      the vast number of proteins encoded by the genome. Display technologies provide
      powerful tools for obtaining antibodies. Aside from the preservation of natural
      antibody repertoires, they are capable of exploiting diversity by DNA
      recombination to create very large libraries for selection of novel molecules. In
      contrast to in vivo immunization processes, display technologies allow selection
      of antibodies under in vitro-defined selection condition(s), resulting in
      enrichment of antibodies with desired properties from large populations. In
      addition, in vitro selection enables the isolation of antibodies against
      difficult antigens including self-antigens, and this can be applied to the
      generation of human antibodies against human targets. Display technologies can
      also be combined with DNA mutagenesis for antibody evolution in vitro. Some
      methods are amenable to automation, permitting high-throughput generation of
      antibodies. Ribosome display is considered as representative of the next
      generation of display technologies since it overcomes the limitations of cell
      based display methods by using a cell-free system, offering advantages of
      screening larger libraries and continuously expanding new diversity during
      selection. Production of display-derived antibodies can be achieved by choosing
      one of a variety of prokaryotic and eukaryotic cell-based expression systems. In
      the near future, cell-free protein synthesis may be developed as an alternative
      for large-scale generation of antibodies.

PMID- 16000088
TI  - Advanced nanoscale separations and mass spectrometry for sensitive high
      throughput proteomics.
AB  - Recent developments in combined separations with mass spectrometry for sensitive
      and high-throughput proteomic analyses are reviewed herein. These developments
      primarily involve high-efficiency (separation peak capacities of approximately
      10(3)) nanoscale liquid chromatography (flow rates extending down to
      approximately 20 nl/min at optimal liquid mobile-phase separation linear
      velocities through narrow packed capillaries) in combination with advanced mass
      spectrometry and in particular, high-sensitivity and high-resolution Fourier
      transform ion cyclotron resonance mass spectrometry. Such approaches enable
      analysis of low nanogram level proteomic samples (i.e., nanoscale proteomics)
      with individual protein identification sensitivity at the low zeptomole level.
      The resultant protein measurement dynamic range can approach 10(6) for nanogram
      sized proteomic samples, while more abundant proteins can be detected from
      subpicogram-sized (total) proteome samples. These qualities provide the
      foundation for proteomics studies of single or small populations of cells. The
      instrumental robustness required for automation and providing high-quality
      routine performance nanoscale proteomic analyses is also discussed.

PMID- 16000089
TI  - The role of mechanical stresses in angiogenesis.
AB  - Angiogenesis is the formation of new capillary blood vessels from preexisting
      vessels. It is involved in many normal and diseased conditions, as well as in the
      application of tissue-engineered products. There has been extensive effort made
      to develop strategies for controlling pathological angiogenesis and for promoting
      vascularization in biomedical engineering applications. Central to advancing
      these strategies is a mechanistic understanding of the angiogenic process.
      Angiogenesis is tightly regulated by local tissue environmental factors,
      including soluble molecules, extracellular matrices, cell-cell interactions, and
      diverse mechanical forces. Great advances have been made in identifying the
      biochemical factors and intracellular signaling pathways that mediate the control
      of angiogenesis. This review focuses on work that explores the biophysical aspect
      of angiogenesis regulation. Specifically, we discuss the role of cell-generated
      forces, counterforces from the extracellular matrix, and mechanical forces
      associated with blood flow and extravascular tissue activity in the regulation of
      angiogenesis. Because angiogenesis occurs in a mechanically dynamic environment,
      future investigations should aim at understanding how cells integrate chemical
      and mechanical signals so that a rational approach to controlling angiogenesis
      will become possible. In this regard, computational models that incorporate
      multiple epigenetic factors to predict capillary patterning will be useful.

PMID- 16000091
TI  - The nursing shortage and developing countries: an ethical dilemma.

PMID- 16000090
TI  - Nitric oxide formation in acutely rejecting cardiac allografts correlates with
      GTP cyclohydrolase I activity.
AB  - Inducible nitric oxide synthase (iNOS) is a prominent component of the complex
      array of mediators in acute graft rejection. While NO production is determined by
      iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP
      cyclohydrolase I, has been considered critical in sustaining NO production. In
      the present study, we examined time-dependent changes in iNOS and GTP
      cyclohydrolase I in rat cardiac allografts. The increase in iNOS protein and mRNA
      in allografts was similar at POD4 (post-operative day 4) and POD6. However, the
      peak increase in intragraft NO level at POD4 was not sustained at POD6. This
      disparity could not be explained by any decrease in iNOS enzyme activity measured
      ex vivo with optimal amounts of substrate and cofactors. Lower iNOS activity
      could be explained by changes in total biopterin levels in allografts at POD4
      that was decreased to baseline at POD6. Changes in biopterin production
      correlated with lower GTP cyclohydrolase I protein levels but not by any change
      in GTP cyclohydrolase I mRNA. Functionally, allografts displayed bradycardia and
      distended diastolic and systolic dimensions at POD6 but not at POD4. Likewise,
      histological rejection scores were increased at POD4 but with a secondary
      increased stage at POD6. It is hypothesized that the dissimilar amounts of NO at
      early and later stages of rejection is due to uncoupling of iNOS arising from
      disproportionate synthesis of BH4. These findings provide insight into a
      potential pathway regulating NO bioactivity in graft rejection. Such knowledge
      may potentially assist in the design of newer strategies to prevent acute graft
      rejection.

PMID- 16000092
TI  - Clients' perceptions of support received from health visitors during home visits.
AB  - AIMS AND OBJECTIVES: The current study sought to identify how many mothers from
      149 visits carried out by seven health visitors identified support as a feature
      of the visit, whether this type of support was unique to the health visitor and
      what support meant to them. These responses were then compared with the
      taxonomies of social support from the social support literature. BACKGROUND: Some
      studies of client perceptions describe support as an element of home visits by
      health visitors. However, the importance, relevance and impact on the client of
      this support are not described in detail. Social support theory suggests that
      there are tangible benefits to people's well-being and their ability to cope with
      various challenges that may arise from individuals' perceptions of receiving
      support. DESIGN: Qualitative study using semistructured interviews. METHODS:
      Seven volunteer health visitors recruited 149 women into the study. These clients
      were interviewed by the researcher, usually within one week of the home visit by
      their health visitor. The discussions were audio-taped and the resulting
      transcripts analysed using content analysis. FINDINGS: Thirty-seven women
      identified receiving support which they said was only available from the health
      visitor. The relevance of this support to the mother and the impact on her well
      being varied within the group suggesting differing perceptions of support by
      clients according to their personal situation. There was a correspondence between
      the descriptions of support given by the women and the taxonomies of social
      support from the social support literature. CONCLUSION: For some interactions
      between clients and their health visitors the existing theory of social support
      may provide an explanation of how health visitors contribute to clients'
      perceived ability to cope and well-being. RELEVANCE TO CLINICAL PRACTICE: Social
      support may be defined as a possible outcome of health visiting. This concept
      will have use within educational programmes to demonstrate to students how health
      visiting can have an impact on clients' well-being. Similarly, the concept could
      be used to investigate and record health visiting practice.

PMID- 16000093
TI  - Pain: a review of three commonly used pain rating scales.
AB  - AIMS AND OBJECTIVES: This review aims to explore the research available relating
      to three commonly used pain rating scales, the Visual Analogue Scale, the Verbal
      Rating Scale and the Numerical Rating Scale. The review provides information
      needed to understand the main properties of the scales. BACKGROUND: Data
      generated from pain-rating scales can be easily misunderstood. This review can
      help clinicians to understand the main features of these tools and thus use them
      effectively. METHOD: A MedLine review via PubMed was carried out with no
      restriction of age of papers retrieved. Papers were examined for methodological
      soundness before being included. The search terms initially included pain rating
      scales, pain measurement, Visual Analogue Scale, VAS, Verbal Rating Scale, VRS,
      Numerical/numeric Rating Scale, NRS. The reference lists of retrieved articles
      were used to generate more papers and search terms. Only English Language papers
      were examined. CONCLUSIONS: All three pain-rating scales are valid, reliable and
      appropriate for use in clinical practice, although the Visual Analogue Scale has
      more practical difficulties than the Verbal Rating Scale or the Numerical Rating
      Scale. For general purposes the Numerical Rating Scale has good sensitivity and
      generates data that can be statistically analysed for audit purposes. Patients
      who seek a sensitive pain-rating scale would probably choose this one. For
      simplicity patients prefer the Verbal Rating Scale, but it lacks sensitivity and
      the data it produces can be misunderstood. RELEVANCE TO CLINICAL PRACTICE: In
      order to use pain-rating scales well clinicians need to appreciate the potential
      for error within the tools, and the potential they have to provide the required
      information. Interpretation of the data from a pain-rating scale is not as
      straightforward as it might first appear.

PMID- 16000094
TI  - Chronic obstructive pulmonary disease: a phenomenological study of patients'
      experiences.
AB  - AIM: The purpose of this study is to explore the experience of living with
      chronic obstructive pulmonary disease by investigating the subjective phenomenon
      as described by the patient. BACKGROUND: Chronic obstructive pulmonary disease is
      now recognized as one of the most common chronic respiratory diseases in the
      United Kingdom, with a high prevalence of morbidity and mortality. As the disease
      progresses, symptoms increase which gradually influence all aspects of the lives
      of those affected by it. METHOD: A phenomenological approach was identified as
      the most appropriate method to gain an understanding of living with chronic
      obstructive pulmonary disease. The data were obtained from 10 participants using
      unstructured interviews to capture detailed experiences verbatim. Analysis, based
      on the framework of Diekelmann et al. (The NLN Criteria for Appraisal of
      Baccalaureate Programs: A Critical Hermeneutic Analysis, NLN Press, New York,
      1989), was employed to interpret the data and determine shared themes that
      evolved during the course of the research. RESULTS: The data revealed valuable
      insights, from a patient's perspective, into the impact chronic obstructive
      pulmonary disease had on their daily lives. The accounts obtained from
      participants, many of who had severe chronic obstructive pulmonary disease,
      illustrate the detrimental effects of this debilitating disease. Breathlessness
      was identified as the most troublesome symptom leading to anxiety, panic and
      fear. Participants also described feeling frustrated and tired because of their
      breathlessness, which led to loss of social activity. This also resulted in a
      loss of their role within the family including loss of intimacy in personal
      relationships. Despite this, half of the participants felt they had a fairly good
      quality of life. CONCLUSION: The use of phenomenology as a research methodology
      fulfilled the aim of gaining a greater understanding of the experiences of living
      with chronic obstructive pulmonary disease. It provided valuable insights into
      how patients view the overall impact and their subsequent degree of coping with
      chronic obstructive pulmonary disease from day to day. RELEVANCE TO CLINICAL
      PRACTICE: Whilst there is no cure for chronic obstructive pulmonary disease and
      medical interventions have limited effect, health professionals can do much to
      improve patient's symptoms and experiences of living with chronic obstructive
      pulmonary disease by listening to how their symptoms affect them and adapting
      coping strategies. It is hoped that the themes revealed in this study generate
      additional understanding and insight for future innovative practice.

PMID- 16000095
TI  - Despair and hopelessness in the context of HIV--a meta-synthesis on qualitative
      research findings.
AB  - AIM: The aim of the study was to explore the concepts of despair and hopelessness
      in the context of human immunodeficiency virus based on previous studies.
      BACKGROUND: Some of the consequences of living with human immunodeficiency virus
      or as a significant other to a person with human immunodeficiency virus include
      despair and hopelessness. METHODS: The study is based on five earlier studies
      describing the dynamics of hope (including despair and hopelessness) in adult
      persons living with human immunodeficiency virus. RESULTS: Despair consists of
      two sub-processes. The downward sub-process of despair refers to stopping and
      being stuck in a situation, losing grip and sinking into a narrowing existence,
      focusing on impossibility and losing perspective of the future. Furthermore, the
      downward orientation means questioning the possibility of hope. The upward sub
      process of despair implies fighting against sinking and fighting to rise back up
      with a glimmer of hope. Hopelessness is the polar opposite of hope and includes
      sub-processes of helplessly giving up everything (including hope) and living in
      emptiness in the face of an assumed non-existing future, collapsing mentally, and
      becoming paralyzed without reason to live. CONCLUSIONS: The results of this study
      support the findings of previous studies revealing that despair and hopelessness
      are possible elements in the life situation of persons living with human
      immunodeficiency virus and significant others to persons living with human
      immunodeficiency virus. The results of this study help to define the contents of
      despair and hopelessness, and help us to distinguish one from the other. The dual
      dimensionality of despair has not been pointed out in previous studies and in
      this way the present study offers new information about the phenomenon of
      despair. RELEVANCE TO CLINICAL PRACTICE: The findings of this study offer
      clinical guidelines on a conceptual level about how to detect these phenomena in
      persons living with human immunodeficiency virus and their significant others.
      Furthermore, the findings offer a starting point for interventions used to
      alleviate despair and hopelessness. Suggestions for suitable interventions are
      offered. The results of this study underline the clinical relevance of these
      phenomena in adding new information to the previously documented consequences of
      despair and hopelessness.

PMID- 16000096
TI  - Nursing students' perception of group supervision during clinical training.
AB  - AIM: The aim of this study was to investigate nursing students' perception of and
      satisfaction with clinical group supervision based on a special model, used in
      nursing training. BACKGROUND: Long-standing efforts have been made to create
      supervision models in nursing training that promote personal and professional
      development and prepare nursing students to cope with the complex and demanding
      situations they will face as registered nurses. METHODS: Data were collected from
      nursing students (n = 43) during their clinical training by means of two
      questionnaires. Most questions were concerned with the importance of factors
      involved in the contract and the students' experiences of how these factors were
      covered during the clinical group supervision. FINDINGS: The findings showed
      that, before starting the supervision programme, most all the students expressed
      positive attitudes towards group supervision, but 25% had negative expectations
      as well. At the end of the programme all students thought that group supervision
      had been an important support to them during their training and almost everyone
      wanted to participate in group supervision in the future as registered nurses.
      The findings showed that both the structure and the climate were important for
      the success of the group supervision. RELEVANCE TO CLINICAL PRACTICE: The
      findings will strengthen the model and confirm its usefulness in clinical
      training for nursing students. Using this supervision model, which includes
      reflection about feelings, thoughts and actions, the students will be well
      prepared for demanded situations in their future role as a registered nurse. A
      replication of this study addressed to trained nurses would be valuable.

PMID- 16000097
TI  - Obesity: translation and testing of a survey instrument for use in Taiwan.
AB  - AIM AND OBJECTIVES: The purpose of this paper is to describe a cross-cultural
      translation and validation methodology recommended by Vallerand. The translation
      technique has seven steps and ensures the instrument provides data that are valid
      and reliable. BACKGROUND: Translation of data collection instruments is a
      challenge increasingly being faced by overseas students studying in the West as
      they choose to research contextual issues of relevance to their home culture.
      METHODS: Six of Vallerand's seven steps are used and modified as the methodical
      translation of a survey from English to Mandarin. RESULTS: The results revealed
      there was no significant difference between the original English questionnaire
      and Mandarin questionnaire. The validation study indicated good internal
      consistency. The construct validity of the Mandarin version was determined except
      one item which failed the test. The validation demonstrates only minor effects of
      language translation. CONCLUSION: The Mandarin version thus is a valid tool for
      investigating from the perspective of school nurses, their role and potential
      contribution to health promotion in relation to the prevention of obesity among
      school children in Taiwan. RELEVANCE TO CLINICAL PRACTICE: The results of the
      study will enable school nurses and their managers to reflect critically on their
      contribution to the prevention of obesity among Taiwanese school children. The
      translation technique has enabled the researcher to minimize errors that may have
      occurred in translation. It adds to the quality of the instrument and offers
      opportunities in the future to undertake cross-cultural comparison in an issue of
      great concern globally.

PMID- 16000098
TI  - Nurse consultants: their characteristics and achievements.
AB  - AIM: This paper reports one aspect of a larger study of nursing research
      strategies in one English region, focusing particularly on nurse consultants'
      characteristics and achievements in the role. BACKGROUND: Nurse consultant posts
      have only been established in the United Kingdom since 1999 and, although much
      comment has appeared in the professional literature, there is very little
      research-based evidence of how the roles are developing. The role is intended to
      integrate four domains: expert practice; professional leadership and consultancy;
      education, training and development; and practice and service development.
      DESIGN: A cross-sectional design, using a convenience sample, was adopted.
      METHODS: Ten nurse consultants working in a variety of settings and specialties
      participated in in-depth, tape-recorded interviews. The data were analysed using
      the Framework approach. RESULTS: Four themes were identified from the data:
      characteristics of the postholder, role achievement, support systems and National
      Health Service influences. The first two themes are discussed in this paper and
      the data show that the nurse consultants varied in terms of their academic
      background and previous experience. Not all had the recommended minimum of
      Master's degree level preparation and some had limited research experience. These
      background characteristics seemed to influence the degree to which they were able
      to achieve the four domains of the role, with those with lower qualifications and
      from a mental health background appearing to struggle most. CONCLUSIONS: New
      appointments to these roles should only be made when candidates possess the
      recommended levels of educational preparation and professional experience of
      change management. It is also important that there is clarity about the scope of
      the role, which should not include management responsibilities. On-going research
      is essential to evaluate how the roles develop for postholders, the extent to
      which they fulfil policymakers' expectations and what difference they make to
      patient care from a patient perspective. RELEVANCE TO CLINICAL PRACTICE: The
      findings show that holders of such posts need to have appropriate previous
      knowledge, skills and personal characteristics, as these seem to influence their
      ability to integrate the four domains of the role and thus achieve the
      requirements of the post.

PMID- 16000099
TI  - Patient education and consumer medicine information: a study of provision by
      Queensland rural and remote area Registered Nurses.
AB  - AIMS AND OBJECTIVES: The aim of the larger study was to ascertain the medication
      practices of registered and enrolled nurses in rural and remote areas of
      Queensland after the introduction of the Health (Drugs and Poisons) Regulation.
      This paper reports on the findings of the role of registered nurses and their
      confidence in the ability to provide information on medications in a way that the
      client understands; the frequency of the provision of information to clients
      prior to discharge; and the frequency of Indigenous Health Workers or
      interpreters for people without English as a first language. BACKGROUND:
      Queensland employs approximately 17% of the Australian registered nurse
      workforce. In 1996 Queensland changed the Health (Drugs and Poisons) Regulation
      to allow specific registered nurses, who had undertaken approved postgraduate
      education and training programmes, to become endorsed for an expanded medication
      practice role. In particular, it allowed endorsed nurses to administer and supply
      (but not prescribe) drugs listed in a drug formulary to certain clients using
      protocols. It was not clear, however, whether the changes to the Regulation
      reflected the scope of practice, thereby providing adequate legal protection for
      the nurse. DESIGN: During 2001-02 an exploration of the medication practices of
      rural and remote area nurses was conducted by the use of a cross-sectional postal
      survey. Phase 1 of the study used a facility audit to ascertain facility
      medication practices and phase 2 of the study used a postal survey to ascertain
      nurses' medication practices. METHOD: All nurses employed in rural and remote
      health facilities in Queensland were eligible to participate in the study. The
      nurse registering authority's (the Queensland Nursing Council) register was used
      to generate a non-proportional stratified random sample. Of the 1999
      questionnaires sent, there were 668 respondents. Of these, 520 were registered
      nurses. RESULTS: The data indicated that there was a difference between endorsed
      and unendorsed registered nurses' medication practice. In particular, it was
      apparent that endorsed registered nurses were more likely to believe they could
      explain the side-effects of medication to clients in a way the patient
      understood; provided medication education to clients on discharge; and used
      Indigenous Health Workers or interpreters to explain medications to those clients
      for whom English was not a first language. However, it was apparent that <50% of
      all Registered Nurses were providing client medication education or using
      Indigenous Health Workers or interpreters. CONCLUSION: It is apparent that the
      changes to the Regulation have ensured that Registered Nurses who have undergone
      postgraduate education to enhance their medication practice are more likely to
      provide client education and consumer medication information. However, the
      results suggest that the majority of registered nurses in Queensland, whilst
      believing they have sufficient knowledge of pharmacology to provide client
      education, often do not provide appropriate medication advice to clients,
      particularly on discharge from the acute setting. RELEVANCE TO CLINICAL PRACTICE:
      It is well recognized that the provision of medication education to clients has
      several benefits to both the client and the health care system. The lack of
      client medication education indicated in this study compromises patient's safety
      as well as their compliance with their medication regime.

PMID- 16000100
TI  - Finding more meaning: the antecedents of uncertainty revisited.
AB  - AIMS AND OBJECTIVES: The objective of this study was to explore the extent to
      which several antecedents explained the uncertainty of men who were undergoing
      the watchful waiting management option for prostate cancer. BACKGROUND:
      Uncertainty plays a significant role in explaining various outcomes in the
      chronically ill. However, little is known about the factors that accompany and
      modify uncertainty. For uncertainty to predict the outcomes of individuals coping
      with illness, it is imperative to understand its accompanying antecedents.
      DESIGN: The study used a correlational single group non-experimental design.
      METHODS: The convenience sample completed a one-time mailed questionnaire aimed
      at measuring the antecedents of uncertainty. RESULTS: A total of 19 participants
      completed questionnaires. The results revealed significant relationships between
      level of education and length of time with illness and uncertainty. Stepwise
      multiple regression indicated that education explained 52% of the variance in
      uncertainty. CONCLUSIONS: This study strengthens the relationship between both
      education and length of time with illness, and uncertainty. It further supports
      the Uncertainty in Illness Model and enhances the understanding of the factors
      that influence uncertainty in the sample. RELEVANCE TO CLINICAL PRACTICE: This
      study assisted in the identification of factors that influence uncertainty in men
      undergoing the watchful waiting management option for prostate cancer. Future
      study should examine the role of antecedents in explaining uncertainty in
      additional populations and using alternative measures, when necessary.

PMID- 16000101
TI  - Drug errors, qualitative research and some reflections on ethics.
AB  - AIMS AND OBJECTIVES: Observational methods as part of a qualitative approach have
      been specifically employed in the study of drug error and have undeniable
      strengths. This position paper will examine some recent research raising a number
      of ethical, and tangentially, methodological issues concerning the qualitative
      study of drug errors within United Kingdom National Health Service hospitals.
      Reflections on the views and ethical conduct of other qualitative researchers are
      provided to contextualize the discussion. BACKGROUND: The impact of a drug error,
      and any resultant adverse event can be significant. The human and financial costs
      are considerable. Establishing an accurate estimation of the frequency of adverse
      event and reporting rates has been difficult; additionally, methodological
      weaknesses in medical error research have sometimes caused further difficulties.
      Unsurprisingly, observational studies and for that matter, a whole range of other
      methods are now being considered in the quest to establish both understanding and
      predictability in relation to medical error. RELEVANCE TO CLINICAL PRACTICE: It
      is argued here that any participants in medical error research should be treated
      in a way that takes account of the prevailing culture of health care and, in the
      United Kingdom, the current ethos of government policy on medical error. This
      requires gaining informed consent, promoting transparency in method, and
      providing the opportunity for participants to learn. Effective error researchers
      can clearly increase the available knowledge in this critical area but ethical
      considerations and their chosen methods should show an appropriate level of
      respect for their participants. Carefully implemented qualitative approaches can
      help realize such respect.

PMID- 16000102
TI  - Risk management of extravasation of cytostatic drugs at the Adult Chemotherapy
      Outpatient Clinic of a university hospital.
AB  - AIMS AND OBJECTIVES: To verify the incidence of extravasation of cytostatic drugs
      in patients treated on an outpatient basis at a university hospital in the city
      of Sao Paulo, Brazil, during the period from 1998 to 2002, and to assess the
      quality of care provided by the nursing team using a protocol adopted for the
      treatment of this adverse event as a parameter. BACKGROUND: The movement for
      quality in healthcare services has been a recent event in Brazil, mainly as the
      result of the Brazilian Program of Hospital Accreditation instituted in 1998.
      Considering the emphasis on risk management, it is important to mention the
      monitoring of the occurrence of extravasations of cytostatic drugs in order to
      improve the quality of nursing care provided to cancer patients. DESIGN AND
      METHODS: An evaluative study with a descriptive, prospective and longitudinal
      design was conducted, based on the documentary analysis of the notification of
      216 extravasations of vesicant and irritant drugs that occurred between 1998 and
      2002 and the corresponding prescriptions of cold or hot compresses. RESULTS: The
      mean incidence of extravasations ranged from 0.2 to 1.4% over the five years of
      the study. Incorrect prescription of the type of compress was observed for three
      patients. Undesired effects were ulcers caused by the extravasation of
      vinblastine and dacarbazine in two cases. CONCLUSIONS: The low incidence of both
      extravasation and tissue damage demonstrates the adequate quality of nursing care
      provided to cancer patients at the outpatient clinic studied. However, the
      identification of the lack of 12 records of thermal treatment and of three
      erroneous prescriptions requires the implementation of educational measures to
      prevent these types of incident. RELEVANCE TO CLINICAL PRACTICE: The relevance of
      this study to clinical practice is to increase the awareness and involvement of
      the nursing team in the maintenance of a continuous surveillance system of the
      process and results of chemotherapy administration in order to increase the
      quality of care and the safety of the patient.

PMID- 16000103
TI  - Radical prostatectomy: men's experiences and postoperative needs.
AB  - AIMS AND OBJECTIVES: This study sought to explore men's experiences after radical
      prostatectomy and whether they perceived their preoperative teaching adequately
      prepared them for postoperative recovery. Tape-recorded telephone and face-to
      face interviews were conducted at days 2, 7 and 21, and 3 and 12 months
      postdischarge. BACKGROUND: Although verbal and written instruction about
      postoperative expectations and care are provided routinely before radical
      prostatectomy, patients express concern about a lack of preparation in managing
      urinary incontinence and erectile dysfunction. DESIGN: This qualitative
      descriptive study explored in-depth men's experiences during the year following
      their surgery. METHODS: Multiple, tape-recorded, semistructured telephone
      interviews were conducted with 17 participants and a single, in-depth, face-to
      face interview was conducted 12 months postoperatively with a subset of five men
      selected for their reflective and descriptive abilities. RESULTS: Although
      participants received comprehensive written and verbal information
      preoperatively, it was not sufficient to foster their management of all
      postoperative sequelae. Telephone follow-up, used as a data collection strategy,
      was helpful in fostering adjustment after surgery and relieved anxiety caused by
      side effects of surgery and unanswered questions. CONCLUSIONS: Pre- and
      postoperative teaching needs to make allowances for the impact of stress on the
      recall and processing of information. Written information in itself is not
      adequate to answer necessary questions and provide reassurance. Follow-up
      telephone support is recommended as a way of fostering adjustment after surgery.
      RELEVANCE TO CLINICAL PRACTICE: This study shows that: (i) Written information in
      itself is not adequate to answer necessary questions and provide reassurance,
      (ii) Nurses need to be prepared, both educationally and psychologically, to
      observe non-verbal cues and to address questions and concerns that are rarely
      voiced in ways that indicate their significance to the person and (iii) Men may
      not speak about sexuality issues in ways that accurately reflect the extent of
      their worry and/or distress about erectile dysfunction.

PMID- 16000104
TI  - Lucidity in a woman with severe dementia related to conversation. a case study.
AB  - AIMS AND OBJECTIVES: The aim of this study was to explore the presence of
      lucidity in a woman with severe dementia during conversations and whether it
      occurred when conversational partners or the woman with severe dementia initiated
      the conversation topics about the present, past or future time and whether she
      was presented with support or demands during the conversation. BACKGROUND:
      Communication problems as well as episodes of lucidity in people with dementia
      are reported in the literature. DESIGN: A researcher held 20 hours of
      conversation with a woman with severe dementia. A daughter participated for about
      three and a half hours. The conversation was tape-recorded and transcribed
      verbatim. METHODS: The text was divided into units of analysis. Each unit of
      analysis was then assessed separately and discussed among the authors. Chi-square
      tests and logistic regression analysis were performed. An ethics committee
      approved the study. RESULTS: The woman as initiator of the conversation topic and
      support to the women during conversation from the conversation partner were found
      to be the most significant factors explaining lucidity, while conversation about
      the present or past time showed no connection with lucidity. Very few topics (n =
      7) concerned future time and they were not used in the statistical analysis. The
      researcher initiated 41%, the woman 43% and the daughter 16% of the topics.
      Support was registered in 49%, demands in 15% and both support and demands in 16%
      of the units of analysis. There were 58% topics about present and 40% about the
      past time. CONCLUSIONS: The presented study is a case study and the results
      cannot be generalized. For the woman with severe dementia, lucidity was promoted
      by the conversational parties carefully focusing on conversation topics initiated
      by the woman while supporting her during conversation. RELEVANCE TO CLINICAL
      PRACTICE: To share the same perception of reality, focusing on the topics
      initiated by the patient with severe dementia and a supporting attitude to what
      the patient tells, will hopefully give more episodes of lucidity in the patient.
      This approach in caring for patients with severe dementia might give more meaning
      and well-being to the conversational partners in daily care.

PMID- 16000105
TI  - The nature of nursing care and rehabilitation of female stroke survivors: the
      perspective of hospital nurses.
AB  - AIMS AND OBJECTIVES: The aim of this study was to explore the nature of nursing
      care and rehabilitation of female stroke survivors, as described by hospital
      nurses. The objectives were to uncover how the nurses perceived the care of
      female stroke survivors and to explore whether, and in what way, the nurses paid
      attention to the fact that the patients were women. BACKGROUND: Nursing care is
      an important aspect of the rehabilitation of stroke survivors. Little attention
      has been paid to gender differences in the health care system in general and in
      the nursing profession in particular, although it is reasonable to think that
      gender issues may have important implications in the rehabilitation process
      following a stroke. DESIGN: Design was phenomenological with feminist
      perspective. METHODS: The nurses were interviewed in-depth. In the data analysing
      process we were inspired by Giorgi's phenomenological method. RESULTS: The nurses
      were focusing primarily on functional and practical aspects of the women's
      situation. They perceived the rehabilitation process predominately from a
      professional rather than the patient point of view, and from a non-conscious and
      primarily gender-neutral perspective. CONCLUSIONS: The results indicate that the
      nurses perceived nursing care primarily in terms of practical actions to promote
      the body's functional and practical abilities. Little attention was directed to
      the stroke survivors' experiences of their life body, nor to the fact that the
      patients were women. RELEVANCE TO CLINICAL PRACTICE: In order to promote care
      from the perspective of the female stroke survivors, we believe it is necessary
      to attend to the life experiences of the patient, which also mandates paying
      attention to how gender has an impact on their diseased bodies, every day life,
      values and preferences in the situation.

PMID- 16000106
TI  - Commentary on Strand ML, Benzein E & Saveman B-I (2004) Violence in the care of
      adult persons with intellectual disabilities. Journal of Clinical Nursing 13, 506
      514.

PMID- 16000108
TI  - To Mander R (2004) commentary on Nystedt et al. (2004).

PMID- 16000109
TI  - Mycoplasma mastitis: a review of transmission and control.
AB  - The Mycoplasma sp. that cause mastitis are simple, cell wall-less, bacteria that
      can colonize and cause diseases in other extramammary sites in the bovine.
      Prevalence of mycoplasma mastitis appears to be increasing in many locations
      throughout the world. The best method to identify this group of pathogens is
      through direct culture on mycoplasma agar media. However, limitations with this
      culture procedure are the duration of culture, 10 days, special conditions
      required and thus added expense, and the lack of primary specificity to
      distinguish between true pathogens and commensal organisms. Thus culture of bulk
      tank milk samples has been advocated as a primary screening method to determine
      the mycoplasma status of a herd. This monitoring system is reasonably successful
      but the sensitivity of detection of Mycoplasma sp. in bulk tank milk is affected
      by a significant minority of cows that might shed the organism at levels below
      the threshold of detection. Contagious mastitis control procedures have been
      effective in controlling outbreaks of mycoplasma mastitis. Yet new methods of
      control might be warranted, methods that may prevent the outbreak. Current data
      suggests that a significant number of new outbreaks may occur via internal or
      animal-to-animal transmission of mycoplasma mastitis pathogens from asymptomatic
      carriers.

PMID- 16000110
TI  - Classical swine fever (CSF) in wild boar: the role of the transplacental
      infection in the perpetuation of CSF.
AB  - Thirty-four pregnant wild sows and their unborn progeny derived from an
      endemically infected population in the district of Nordvorpommern (Mecklenburg
      Western Pomerania) were investigated for classical swine fever virus (CSFV) and
      antibodies. During the last 2.5 years of the epidemic, 20 out of 34 pregnant wild
      sows investigated were serologically positive. No CSFV or viral RNA was detected
      in organs derived from these animals and their progeny. This indicates that young
      wild boars persistently infected by transplacental virus transmission do not play
      a crucial role in the perpetuation of CSFV in wild boar. Other factors seem to be
      more important for the establishment of CSF as well as for virus perpetuation in
      the population.

PMID- 16000111
TI  - PCR for detection of Mycobacterium tuberculosis in experimentally infected dogs.
AB  - The susceptibility of dogs to infection with Mycobacterium tuberculosis was
      studied through different ways of experimental infection. The examination shows,
      that in most cases the disease runs subclinically with pathological changes
      localized mainly in the lungs, lymph nodes, small intestines, liver, kidneys and
      spleen. Histological findings demonstrate granulomatous inflammation with
      caseosation and predominance of epitheloide macrophages and single lymphocytes.
      Tissue samples from internal organs of experimentally infected dogs as well as
      non-infected but contact animals were investigated by direct PCR. Specific PCR
      products were obtained in 44 of 96 studied samples. Eighty-three (86.5%) of PCR
      results coincided with bacteriological finds, 82 (85.4%) with the pathological
      and 71 (74.0%) simultaneously with bacteriological and pathological results. The
      observed specific DNA products in tissue samples of infected and non-infected
      dogs demonstrate significant sensitivity of PCR method. It could be assumed that
      the transmission of M. tuberculosis infection is possible by close contact
      between ill and healthy dogs and that the naturally infected dogs or dogs
      suffering from tuberculosis may serve as a permanent source of infection to
      humans and other animals.

PMID- 16000112
TI  - Studies of the efficacy of Enterocoliticin, a phage-tail like bacteriocin, as
      antimicrobial agent against Yersinia enterocolitica serotype O3 in a cell culture
      system and in mice.
AB  - The efficacy of enterocoliticin, a phage tail-like bacteriocin, as antimicrobial
      compound against infections with pathogenic Yersinia enterocolitica serotype O3
      strains was assessed. In cell cultures, which were infected with the Y.
      enterocolitica strains 13 169 or 6471/76, bactericidal activity of
      enterocoliticin was found for bacteria adhering to the surface of eukaryotic
      cells, whereas bacteria, which had invaded the eukaryotic cells, were not
      accessible to the bacteriocin. The interaction of enterocoliticin with Y.
      enterocolitica was further examined in animals. Female BALB/c mice were
      experimentally infected with the two Y. enterocolitica strains and
      enterocoliticin was applied as antimicrobial compound by the oral route.
      Experimental variations concerning the infectious doses of the Y. enterocolitica
      strains and the time points of application of the bacteriocin were investigated.
      The increase of the Yersinia CFU titre in animals was retarded at time points
      shortly after the application of enterocoliticin indicating that the particles
      were effective on recently introduced Yersinia. The repeated application of
      enterocoliticin, however, did not prevent the colonization of the
      gastrointestinal tract by Yersinia.

PMID- 16000113
TI  - Role of microfilaments and microtubules in the invasion of EPC cells by Aeromonas
      hydrophila.
AB  - The influence of the cytoskeleton on the invasion of Aeromonas hydrophila strain
      AhJ-1, isolated from diseased fish, in the monolayer cell of epithelioma
      papillosum cells of carp (EPC) was evaluated by the recovery of gentamicin
      resistant bacteria from Triton X-100 cell lysates. The depolymerization of
      microfilaments (MF) by cytochalasin B and D inhibited the uptake of A. hydrophila
      in a dose-dependent manner and that of microtubules (MT) by colchicines and
      nocodazole did not affect the invasion of A. hydrophila in EPC cells
      significantly. The invasion frequency decreased approximately 62% with the
      addition of 0.1 microg/ml cytochalasin D and nearly 86% by the addition of 5.0
      microg/ml. Invasion decreased approximately 49% and 83% by addition of
      cytochalasin B in a concentration of 2.5 microg/ml and 10.0 microg/ml. Colchicine
      and nocodazole, inhibitors of MT formation appears to have little effect on the
      invasion of EPC cells by strain Ah J-1. Thus MF formation, but not MT formation
      seems to play an important role in the internalization of A. hydrophila J-1.

PMID- 16000114
TI  - Campylobacter spp. in dogs and cats in Switzerland: risk factor analysis and
      molecular characterization with AFLP.
AB  - A 1-year cross-sectional study was carried out to determine the prevalence, risk
      factors for carriage, and genetic diversity of Campylobacter spp. in healthy dogs
      and cats in Switzerland. Veterinary practitioners collected samples from 1268
      animals (all ages) presented for vaccination. The prevalence of Campylobacter
      spp. in 634 dogs and 596 cats that were eligible for the study was 41.2%
      (confidence interval 95%: 37.3-45.1%) and 41.9% (CI 95%: 37.9-46%), respectively.
      Risk factors identified for carriage of Campylobacter jejuni were found to be
      different from risk factors for C. upsaliensis/C. helveticus. Young animals (< or
      =3 years) had significantly higher odds of carrying C. upsaliensis/C. helveticus
      than older animals (OR 1.8-3.3), whereas for C. jejuni carriage, the age was not
      a risk factor. Amplified fragment length polymorphism (AFLP) genotyping revealed
      heterogeneity among C. jejuni strains and was found to clearly separate C.
      helveticus from C. upsaliensis. It was shown that cats more often carry C.
      helveticus with an estimated prevalence of 28.2%, whereas dogs mainly are
      carrying C. upsaliensis.

PMID- 16000115
TI  - Systemic and local antibody responses after experimental infection with
      Actinobacillus pleuropneumoniae in piglets with passive or active immunity.
AB  - The objectives of the present study was to describe different dynamics of humoral
      immune responses to experimental infection in piglets of different stages of
      infection and immunity. Two groups of piglets originating from non-immune (group
      1) and immune (group 2) sows at the age of 3 weeks were subdivided as follows: a
      half of each group of piglets was exposed to a low-dose infection with
      Actinobacillus pleuropneumoniae (APP) strain 9. At the age of 8 weeks, all four
      groups of piglets were challenged with a high infection dose of APP of the same
      strain. Isotype characterization of the specific antibodies in sera and in
      bronchoalveolar lavage fluids (BALF) to a lipopolysaccharide was carried out,
      besides monitoring clinical signs and post-mortem examinations. A typical primary
      immune response was observed in specific antibody-free piglets infected with a
      challenge infection. Colostrum-derived immunoglobulin-G (IgG) antibodies
      persisted in sera and BALF of piglets up to the age of 8 weeks. However, they did
      not prevent induction of specific-primary antibody response, either in 8 or 4
      weeks of age, when levels of specific colostrum-derived antibodies were still
      high. It was demonstrated by the increase of specific IgM antibodies in sera. The
      infection induced an increase in the levels of IgA antibodies in BALF regardless
      the severity of infection and presence of specific colostrum-derived antibodies.
      The specific antibodies of IgG isotype increased only in BALF from piglets
      without colostrum-derived antibodies.

PMID- 16000116
TI  - Dermatitis in a dairy herd caused by Pelodera strongyloides (Nematoda:
      Rhabditidae).
AB  - A high rate (25%) of infestation of heifers in a dairy cattle herd caused by the
      saprophytic nematode Pelodera strongyloides is described. Management (crowded)
      and environmental conditions (moist and filthy) as well as the climate
      (temperature) apparently favoured the existence and continuation of the
      nematodes. These infested a large number of heifers by causing dermatitis in skin
      areas, which were in contact with the contaminated environment. The dermatitis is
      characterized by a marked thickening of the skin, which became wrinkled and
      scurfy with alopecia. Pruritus was not observed.

PMID- 16000117
TI  - Statistical evaluation of classical swine fever surveillance plans in Italy (1995
      2003).
AB  - Summary Surveillance plans were carried out in Italy from 1995 to 2003, with the
      main aim of controlling the possible circulation of low-virulence classical swine
      fever viral strains. The repetition of a serological monitoring programme over
      several years, with constantly negative results, can prove the absence of the
      infection while increasing the degree of confidence. In our case, in 2003, after
      eight repetitions of the surveillance plan, the probability that there was at
      least one infected farm reached 0.006%. Therefore, on the basis of the results of
      the sampling carried out from 1995 to 2003, we may state that there is no endemic
      infection, even because of a low virulence virus, in continental Italy.

PMID- 16000118
TI  - Relationship between temporary inhibition and structure of disulfide-linkage
      analogs of marinostatin, a natural ester-linked protein protease inhibitor.
AB  - A 12-residue marinostatin [MST(1-12): (1)FATMRYPSDSDE(12)] which contains two
      ester linkages of Thr(3)-Asp(9) and Ser(8)-Asp(11) strongly inhibits subtilisin.
      In order to study the relationship between the inhibitory activity, structure,
      and stability of MST, MST analogs were prepared by changing ester linkages to a
      disulfide linkages. The analogs without the disulfide linkage between 3 and 9
      positions lost their inhibitory activity. The K(i) value of 1SS(C(3)-C(9))
      ((1)FACMRYPSCSDE(12)), which has a single disulfide linkage of Cys(3)-Cys(9) was
      comparable with those of MST(1-12) and MST-2SS ((1)FACMRYPCCSCE(12)), a doubly
      linked analog of Cys(3)-Cys(9) and Cys(8)-Cys(11). However, 1SS(C(3)-C(9)) and
      MST-2SS showed temporary inhibition, but not MST(1-12): These analogs were
      inactivated after incubation with subtilisin for 30 min, and were specifically
      hydrolyzed at the reactive site. (1)H NMR study showed that 1SS(C(3)-C(9)) has
      two conformations, which contain a cis- (70%) or trans- (30%) Pro residue, while
      MST-2SS as well as MST(1-12) takes a single conformation containing only a cis
      Pro residue. Hydrogen-deuterium exchange rate of the Arg(5) (P1') NH proton of
      the MST analogs was about 100 times faster than that of MST(1-12). These results
      indicate that the linkage between the positions 8 and 11 plays a role for fixing
      the cis-conformation of the Pro(7) residue, and that the linkage between 3 and 9
      is indispensable for the inhibition, but not enough for stable protease-inhibitor
      complex.

PMID- 16000119
TI  - Protein dynamics of bovine dentin phosphophoryn.
AB  - Bovine dentin phosphophoryn (BDP), a protein rich in aspartyl (Asp) and o
      phosphoseryl [Ser(P)] residues, is synthesized by odontoblasts and believed to be
      involved in matrix-mediated biomineralization of dentin. The elucidation of the
      structure-function relationship of phosphophoryn has been a challenge because of
      its high-molecular weight, high negative charge, repetitive sequence, and
      lability. We have used the dynamic behavior of the (1)H NMR signal at 600 MHz to
      provide insight into the molecular dynamics of phosphophoryn. Our results
      indicate that phosphophoryn is a molecule of uniformly high mobility, thus
      belonging to a recently identified class of intrinsically disordered proteins
      that are characterized by sequences of low complexity and rich in polar and
      charged residues. The significance of our results is that phosphophoryn, because
      of its uniform nature has the potential to be replaced by biomimetic synthetic
      peptide analogs that together with amorphous calcium phosphate may lead to the
      development of novel, nontoxic, apatite-based dental restorative materials.

PMID- 16000120
TI  - Effects of branched beta-carbon dehydro-residues on peptide conformations:
      syntheses, crystal structures and molecular conformations of two tetrapeptides:
      (a) N-(benzyloxycarbonyl)-DeltaVal-Leu-DeltaPhe-Leu-OCH3 and (b) N
      (benzyloxycarbonyl)-DeltaIle-Ala-DeltaPhe-Ala-OCH3.
AB  - The roles of branched beta-carbon dehydro-residues in the design of peptide
      conformations have not been systematically explored so far. In order to determine
      the effects of branched beta-carbon dehydro-residues on the peptide
      conformations, two N-protected tetrapeptides containing new combinations of
      DeltaVal and DeltaPhe in (a) N-(benzyloxycarbonyl)-DeltaVal-Leu-DeltaPhe-Leu
      OCH(3) and DeltaIle and DeltaPhe in (b) N-(benzyloxycarbonyl)-DeltaIle-Ala
      DeltaPhe-Ala-OCH(3) were synthesized by solution procedure. The crystal
      structures of these peptides were determined by X-ray diffraction methods. Single
      crystals of both peptides were grown by slow evaporation method from their
      solutions in acetone-water mixtures (80 : 20) at 25 degrees C. The crystals of
      these peptides belong to the orthorhombic space group P2(1)2(1)2(1) with cell
      dimensions of a = 12.342(1) A, b = 15.659(1) A, c = 18.970(1) A for peptide (a)
      and a = 8.093(1) A, b = 15.791(1) A, c = 23.816(1) A for peptide (b) having Z = 4
      in the unit cells of both peptides. The structures were refined by full-matrix
      least-squares procedure to R-factors of 0.076 and 0.052 respectively. Both
      peptides adopt the right-handed 3(10)-helical conformations stabilized by two
      intramolecular (i + 3-->i) hydrogen bonds between the CO of N-terminal
      benzyloxycarbonyl (Cbz) group and the NH of residue at position 3, and between
      the CO of residue at position 1 and NH of the residue at position 4. The two
      consecutive 10-membered rings formed by the hydrogen bonds have dihedral angles
      corresponding to the standard values for type III beta-turns. DeltaVal and
      DeltaIle in peptides (a) and (b) respectively are located at the (i + 1) position
      of the first beta-turn while DeltaPhe is located at the (i + 2) position of the
      second beta-turn. In the crystals, the molecules are linked head to tail by
      intermolecular hydrogen bonds to form long helical chains. The axes of helices
      are parallel to the b-axes while the neighbouring helices run in the opposite
      directions. The crystal packings are further stabilized by van der Waals forces
      between the columns of molecular packings.

PMID- 16000121
TI  - Furanoid sugar amino acids as dipeptide mimics in design of analogs of vasoactive
      intestinal peptide receptor binding inhibitor.
AB  - In this study we describe the development of peptidomimetic analogs of the potent
      vasoactive intestinal peptide receptor binding inhibitor, Leu(1) -Met(2) -Tyr(3) 
      Pro(4) -Thr(5) -Tyr(6) -Leu(7) -Lys(8) -OH 1, by incorporating furanoid sugar
      amino acids (SAAs) 2-4 into the molecule. The furanoid SAAs 2-4 were used as
      dipeptide isosteres to replace Tyr(3) -Pro(4) or Pro(4) -Thr(5) in sequence 1.
      The resulting analogs 5-9 were tested for their anti-cancer activities in vitro,
      following the standard MTT assay on a panel of human cancer cell lines. One of
      the potent analogs, 6a was tested in vivo for tumor regression on primary colon
      tumor xenografted nude mice. Our experimental results suggest that many of these
      analogs show either retention or enhancement of biological activity.

PMID- 16000122
TI  - Synthesis and X-ray crystal structure study of the hydroxyurea and hydantoin
      derivatives of L-valine.
AB  - The novel hydroxyurea 5 derivative of L-valine was prepared by aminolysis of N-(1
      benzotriazolecarbonyl)-L-valine cyclohexanemethylamide 4 with hydroxylamine. The
      corresponding hydantoin derivative 6 was synthesized by base catalyzed
      cyclization of the amide 4. The exact stereostructure of hydantoin derivative 6
      has been determined by X-ray crystal structure analysis. The chiral atom of the
      hydantoin ring in 6 has S configuration what is in agreement with its
      configuration in the starting L-valine. The molecules of 6 are joined into
      infinite chains by N-H...O intermolecular hydrogen bond. The infinite chains are
      additionally linked by two C-H...O hydrogen bonds, thus forming two-dimensional
      network. The hydantoin derivative of L-valine 6 and its L-leucine analogue LH
      have similar packing arrangements, so they are homostructural.

PMID- 16000123
TI  - Detection of peptides covalently modified with multiple fatty acids by MALDI-TOF
      mass spectrometry.
AB  - Analysis and characterization of membrane proteins and hydrophobic peptides by
      matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS) is a considerable challenge because of their lower ionization
      efficiency. Detergents are used to solubilize hydrophobic peptides and proteins.
      However, in MALDI-MS, the presence of detergents can cause considerable loss of
      signal intensity. The extent of interference depends on the matrix/sample
      preparation method and experimental conditions. In the present study, we have
      analyzed the MALDI response of multiple fatty acylated peptides in the presence
      of the matrices alpha-cyano-4-hydroxy cinnamic acid (HCCA) and 2,5-dihydroxy
      benzoic acid (DHB). The effect of adding the nonionic detergent n-octylglucoside
      (OG) was also examined. The presence of OG facilitated detection of
      tetrapalmitoylated peptide, particularly when HCCA was used as the matrix. When
      DHB was used as the matrix, good signal intensity was observed in the absence of
      OG. Lower laser pulse rate in the linear mode of analysis resulted in good signal
      intensity for the tetrapalmitoylated peptide. Conditions for obtaining good
      signal intensities for dipalmitoylated and N-myristoyl peptides with both HCCA
      and DHB as matrices were also investigated.

PMID- 16000125
TI  - Oxidative stress as a multiple effector in Fanconi anaemia clinical phenotype.
AB  - Fanconi anaemia (FA) is a genetic disease characterised by bone marrow failure
      with excess risk of myelogenous leukaemia and solid tumours. A widely accepted
      notion in FA research invokes a deficiency of response to DNA damage as the
      fundamental basis of the 'crosslinker sensitivity' observed in this disorder.
      However, such an isolated defect cannot readily account for the full cellular and
      clinical phenotype, which includes a number of other abnormalities, such as
      malformations, endocrinopathies, and typical skin spots. An extensive body of
      evidence pointing toward an involvement of oxidative stress in the FA phenotype
      includes the following: (i) In vitro and ex vivo abnormalities in a number of
      redox status endpoints; (ii) the functions of several FA proteins in protecting
      cells from oxidative stress; (iii) redox-related toxicity mechanisms of the
      xenobiotics evoking excess toxicity in FA cells. The clinical features in FA and
      the in vivo abnormalities of redox parameters are here reconsidered in view of
      the pleiotropic clinical phenotype and known biochemical and molecular links to
      an in vivo prooxidant state, which causes oxidative damage to biomolecules,
      resulting in an excessive number of acquired abnormalities that may overwhelm the
      cellular repair capacity rather than a primary deficiency in DNA repair. FA may
      thus represent a unique model disease in testing the integration between the
      acquisition of macromolecular damage as a result of oxidative stress and the
      ability of the mammalian cell to respond effectively to such damage.

PMID- 16000126
TI  - Etiology of thrombocytopenia in all patients treated with heparin products.
AB  - PURPOSE: To characterize the cause of thrombocytopenia in all patients treated
      with heparin products, to determine the incidence of heparin-induced
      thrombocytopenia (HIT) in unselected hospitalized patients, and to have modern
      data of the magnitude of this problem. METHODS: Retrospective hospital-based
      cohort study. During a random 2-month period, we reviewed the medical records of
      all patients treated with heparin agents, screened them for thrombocytopenia, and
      determined the cause of it. RESULTS: Out of 674 patients who received heparin
      products, 110 (16%) had thrombocytopenia. The most common causes included cancer
      chemotherapy, surgery, sepsis, and medications. Three patients met the clinical
      criteria for HIT. One had antibodies for heparin-platelet factor-4, and received
      a direct thrombin inhibitor. The other two individuals had a clinical syndrome
      that resembled immune HIT, but were not tested for HIT antibodies. One suffered a
      thrombotic episode that led to the death of her fetus. The other died of a
      possible thromboembolism. CONCLUSIONS: This study provides evidence-based data
      for the differential diagnosis of thrombocytopenia after treatment with heparin
      products. Our findings suggest that increased awareness of the HIT syndrome might
      reduce morbidity and mortality. Patients exposed to heparin products, who develop
      thrombocytopenia, should not be overlooked.

PMID- 16000124
TI  - AMPA receptor stimulation increases alpha5beta1 integrin surface expression,
      adhesive function and signaling.
AB  - Integrin proteins are critical for stabilization of hippocampal long-term
      potentiation but the mechanisms by which integrin activities are involved in
      synaptic transmission are not known. The present study tested whether activation
      of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) class glutamate
      receptors increases surface expression of alpha5beta1 integrin implicated in
      synaptic potentiation. Surface protein biotinylation assays demonstrated that
      AMPA treatment of COS7 cells expressing GluR1 homomeric AMPA receptors increased
      membrane insertion and steady-state surface levels of alpha5 and beta1 subunits.
      Treated cells exhibited increased adhesion to fibronectin- and anti-alpha5-coated
      substrates and tyrosine kinase signaling elicited by fibronectin-substrate
      adhesion, as expected if new surface receptors are functional. Increased surface
      expression did not occur in calcium-free medium and was blocked by the protein
      kinase C inhibitor chelerythrine chloride and the exocytosis inhibitor brefeldin
      A. AMPA treatment similarly increased alpha5 and beta1 surface expression in
      dissociated neurons and cultured hippocampal slices. In both neuronal
      preparations AMPA-induced integrin trafficking was blocked by combined antagonism
      of NMDA receptor and L-type voltage-sensitive calcium channel activities but was
      not induced by NMDA treatment alone. These results provide the first evidence
      that glutamate receptor activation increases integrin surface expression and
      function, and suggest a novel mechanism by which synaptic activity can engage a
      volley of new integrin signaling in coordination with, and probably involved in,
      stabilization of synaptic potentiation.

PMID- 16000127
TI  - Self-reported quality of life in elderly patients with aggressive non-Hodgkin's
      lymphoma treated with CHOP chemotherapy.
AB  - We studied the impact of CHOP chemotherapy on the quality of life (QoL) of
      elderly patients with aggressive non-Hodgkin's lymphoma (NHL). 132 patients aged
      65 or older, who participated in a randomized, multicenter trial, completed QoL
      questionnaires (EuroQol-5D, EORTC QLQ-C30 and MFI-20) on 8 predefined time-points
      before, during and following treatment. At baseline, QoL was significantly better
      on almost all dimensions in patients with a lower compared to patients with a
      higher age-adjusted International Prognostic Index (aaPI). During treatment,
      physical and role functioning and global QoL deteriorated and fatigue increased
      in the lower aaPI group, whereas QoL of the higher aaPI group remained stable.
      During follow-up, the QoL was significantly better for patients in complete
      response (CR) or partial remission (PR) than for patients with
      progression/relapse. Soon after completion of therapy, the QoL of the lower aaPI
      group returned to pretreatment levels or better, while patients with higher aaPI
      showed a significant improvement in QoL compared to baseline levels. The effect
      of CHOP on the quality of life of elderly patients could be used in counseling
      this group of patients.

PMID- 16000128
TI  - Combination chemotherapy with gemcitabine and vinorelbine in the treatment of
      relapsed or refractory diffuse large B-cell lymphoma: a phase-II trial by the
      Hellenic Cooperative Oncology Group.
AB  - To investigate the efficacy and toxicity of the combination of gemcitabine and
      vinorelbine in patients with relapsed or refractory diffuse large B-cell lymphoma
      (DLBL), 22 patients with relapsed or refractory DLBL were treated with
      gemcitabine 1000 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8 every 3 wk for a
      maximum of six cycles. Fourteen patients were considered chemosensitive while
      eight patients were considered chemoresistant to the last treatment regimen. All
      22 patients were assessed for response to treatment. Three patients (14%)
      achieved complete remission and eight patients (36%) had partial remission of
      their disease, with an overall response rate of 50%. With a median follow up of
      44 months, the median time to progression (TTP) for all patients was 8.1 months
      while the median overall survival (OS) was 12.9 months. Toxicity was minimal and
      all patients were treated on an outpatient basis. The combination of gemcitabine
      and vinorelbine is an effective and well-tolerated regimen for patients with
      relapsed of refractory DLBL.

PMID- 16000129
TI  - Deoxycoformycin (pentostatin) in the treatment of splenic marginal zone lymphoma
      (SMZL) with or without villous lymphocytes.
AB  - BACKGROUND: Splenic marginal zone lymphoma (SMZL) is an infrequent B-cell
      neoplasm that pursues an indolent course. Signs and symptoms, mostly related to
      hypersplenism, are successfully managed by splenectomy. However, the therapy of
      patients who are not fit for a surgical procedure or who relapse after
      splenectomy, is still an unsettled issue. PATIENTS AND METHODS: We report a phase
      II study on 16 patients with SMZL, three therapy naive and 13 pretreated, all
      showing systemic symptoms or progressive worsening of peripheral cytopenia, who
      were treated with pentostatin at a dose of 4 mg/m2 every other week for 6-10 wk.
      In relapsed patients, the median interval between diagnosis and treatment was 26
      month (range: 8-49). RESULTS: Overall, 68% of the patients showed a clinical
      response. Two out three patients, who received pentostatin as first line therapy,
      attained a complete response (CR). One CR and seven minor or good haematological
      responses were recorded in relapsed patients. Treatment toxicity, mostly
      haematological, proved manageable. With a median follow-up of 35 month the median
      overall survival (OS) is 40 month and the median progression free survival (PFS)
      is 18 month. CONCLUSION: Our data show that pentostatin administered every other
      week has a good degree of activity in the treatment of SMZL and suggest that this
      schedule could be considered a possible therapeutic option for patients who are
      not fit for splenectomy or have relapsed.

PMID- 16000130
TI  - Long-term experience with low-dose interferon-alpha and PUVA in the management of
      early mycosis fungoides.
AB  - OBJECTIVES: Combined high-dose Interferon-alpha and psoralen plus ultraviolet A
      irradiation (PUVA) have been reported to be effective in the treatment of early
      mycosis fungoides (MF); however, our study is the first controlled prospective
      study in the literature exploring the activity and tolerability of the
      combination with low dosages and evaluating further clinical outcome of early-MF
      patients. METHODS: We carried out a multicentric prospective Phase II clinical
      study on 89 patients with early-stage IA to IIA MF treated for 14 months with low
      dose IFN-alpha2b (6-18 MU/wk) and PUVA. Treatment success was analysed in terms
      of freedom from treatment failure. RESULTS AND CONCLUSIONS: Complete remission
      (CR) was achieved in 84% and an overall response rate in 98% of cases: six-month
      CR was associated with a non-confluent skin infiltrate at histology (P = 0.044)
      and 14-month CR with high epidermal CD1a+ dendritic-cell density (P = 0.030). The
      combination protocol was successfully tolerated and the most common reason of
      'failure' was related to relapse and not to toxicity. Sustained remissions were
      achieved in 20% of patients. High CD8+ lymphoid T-cell density was associated
      with a lower relapse rate (P = 0.002). We think that our combination therapy can
      be considered an alternative approach compared with other modalities. Good
      immunological host surveillance in the skin lesions seems to be an optimal basis
      for the therapeutic success.

PMID- 16000131
TI  - Macrocytosis associated with monoclonal gammopathy.
AB  - OBJECTIVE: To report the potential association between unexplained macrocytosis
      and monoclonal gammopathy. METHODS: We retrospectively reviewed the medical
      records of patients who had monoclonal protein detected by serum electrophoresis
      and immunofixation from October 1999 until September 2003 at our institution.
      Patients with concomitant macrocytosis were included in this study. We collected
      data on patient demographics, evaluations performed for macrocytosis, pertinent
      laboratory tests relevant to the diagnosis of monoclonal gammopathy and presence
      of associated hematologic disorders. RESULTS: We identified 258 patients with
      monoclonal gammopathy. Thirty-one (12%) of them had concomitant macrocytosis. Of
      the latter group, 14 (5%) patients had no identifiable cause of macrocytosis
      after thorough evaluation and were considered to have macrocytosis associated
      with monoclonal gammopathy. The median values for mean cell volume and serum
      monoclonal protein were 103.9 fL (range 100.8-109.8) and 1.95 gm/dL (range 0.8
      4.3), respectively. Most patients had IgG (71%) and kappa light chain (79%). All
      of the 11 (of 14) patients who underwent a bone marrow biopsy as part of the
      initial evaluation had megaloblastoid maturation of the erythroid precursors. No
      correlation was found between the level of serum monoclonal protein and the
      degree of macrocytosis (r = +0.48, P = 0.08). After a median follow-up of 22.5
      month (range 3-60+), all but one patient had persistent but stable macrocytosis.
      CONCLUSION: Macrocytosis can be a manifestation of monoclonal gammopathy.
      Disorders associated with monoclonal gammopathy should be considered in the
      differential diagnoses during evaluation of macrocytosis.

PMID- 16000132
TI  - Reduced immune responses to an aseptic inflammation in mice with congestive heart
      failure.
AB  - We previously found that mice with congestive heart failure (CHF) were anemic,
      had decreased bone marrow haematopoiesis and functionally impaired neutrophilic
      granulocytes despite normal blood concentrations of these cells. We now asked if
      CHF-mice could mount an adequate immune response when challenged with an acute
      inflammation. A postinfarction heart failure was induced in mice. Six weeks later
      the mice had developed CHF. At that time a sterile peritonitis was induced by
      injection of a casein digest. Five hours after this injection a marked
      neutrophilia had developed. Specimens were then obtained from peritoneal
      washings, bone marrow and blood. Total bone marrow cell numbers were halved in
      CHF-peritonitis mice compared with sham-peritonitis mice. Bone marrow colony
      forming cell numbers in CHF-peritonitis mice were only 14% of those in sham
      peritonitis mice. The mobilization of leucocytes to the blood was much lower in
      CHF-peritonitis mice than in sham-peritonitis mice (5.6 vs. 8.1 million
      cells/mL), as was the peritoneal influx of these cells (1.6 vs. 4.1 million
      cells). A profound decline (>50%) in the functional activity, determined with
      various in vitro assays, was evident for both neutrophilic granulocytes and
      lymphocytes from CHF-peritonitis mice. Heart failure after myocardial infarction
      in mice may severely compromise their ability to combat an inflammatory
      challenge.

PMID- 16000133
TI  - Acute intestinal obstruction due to intramural haemorrhage in small intestine in
      a patient with severe haemophilia A and inhibitor.
AB  - Patients with severe haemophilia A usually present with joint, gastrointestinal
      and urinary tract haemorrhage. Bleeding elsewhere is often precipitated by pre
      existing pathology or trauma. We report a patient with severe haemophilia A, who
      presented with symptoms of acute intestinal obstruction. He has a factor VIII
      inhibitor and receives recombinant factor VIIa on demand at home. The CT scan of
      abdomen showed dilated small intestine with fluid filled loops and a long segment
      in the jejunum with marked transmural thickening. There was no other pathology in
      the small intestine. These appearances were consistent with intramural
      haemorrhage in the small intestine as the cause of acute obstruction. He was
      managed conservatively with recombinant factor VIIa and this resulted in
      resolution of his symptoms. This case highlights an unusual presentation of
      bleeding in a haemophilia patient. Intestinal obstruction due to haemorrhage in
      the small intestinal wall is extremely rare and only previously reported in a few
      haemophilia patients. It also highlights the effectiveness of conservative
      management with recombinant factor VIIa as opposed to immediate exploratory
      surgery.

PMID- 16000134
TI  - Successful therapy with argatroban for superior mesenteric vein thrombosis in a
      patient with congenital antithrombin deficiency.
AB  - A 38-year-old woman was admitted with superior mesenteric vein (SMV) thrombosis,
      which was refractory to anticoagulation therapy. The plasma antithrombin activity
      was decreased and hardly compensated by concentrated antithrombin preparation due
      to high consumption rate. However, successful anticoagulation was achieved by
      administration of direct thrombin inhibitor, argatroban. Family studies of
      antithrombin activity revealed that she had type I congenital antithrombin
      deficiency. A novel heterozygous mutation in the gene for antithrombin (single
      nucleotide T insertion at 7916 and 7917, Glu 272 to stop in exon 4) was
      identified. Argatroban administration would be effective in the treatment of
      congenital antithrombin deficiency with SMV thrombosis.

PMID- 16000135
TI  - A patient of extramedullary cutaneous and gingival plasmacytomas.

PMID- 16000136
TI  - Failure of rituximab monotherapy in lymphomatoid granulomatosis.

PMID- 16000137
TI  - Which immunization for children after chemotherapy?

PMID- 16000138
TI  - Re-immunisations after childhood leukaemia.

PMID- 16000139
TI  - Do we really know which pediatric cancer patients need revaccination?

PMID- 16000144
TI  - Phosphorylation of tau at serine 416 by Ca2+/calmodulin-dependent protein kinase
      II in neuronal soma in brain.
AB  - It is well known that tau is a good in vitro substrate for Ca2+/calmodulin
      dependent protein kinase II (CaM kinase II). However, it is not clear at present
      whether CaM kinase II phosphorylates tau in vivo or not. Serine 416, numbered
      according to the longest human tau isoform, has been reported to be one of the
      major phosphorylation sites by CaM kinase II in vitro. In this study, we produced
      a specific antibody against tau phosphorylated at serine 416 (PS416-tau).
      Immunoblot analysis revealed that the antibody reacted with tau in the rat brain
      extract which was prepared in the presence of protein phosphatase inhibitors.
      Developmental study indicated that serine 416 was strongly phosphorylated at
      early developmental stages in rat brain. We examined the localization of PS416
      tau in primary cultured hippocampal neurons and the immortalized GnRH neurons
      (GT1-7 cells), which were stably transfected with CaM kinase IIalpha cDNA.
      Immunostaining of these cells indicated that tau was phosphorylated mainly in
      neuronal soma. Interestingly, tau in neuronal soma in Alzheimer's disease (AD)
      brain was strongly immunostained by the antibody. These results suggest that CaM
      kinase II is involved in the accumulation of tau in neuronal soma in AD brain.

PMID- 16000145
TI  - ATP-sensitive potassium channel opener iptakalim protected against the
      cytotoxicity of MPP+ on SH-SY5Y cells by decreasing extracellular glutamate
      level.
AB  - Mounting evidence reveals that ATP-sensitive potassium (K(ATP)) channel openers
      (KCOs) exert significant neuroprotection in vivo and in vitro in several models
      of Parkinson's disease (PD). However, the mechanisms are not well understood. In
      this study, we demonstrated that SH-SY5Y cells expressed mRNA and proteins for
      Kir6.1, Kir6.2, SUR1 and SUR2 subunits of K(ATP) channels. Moreover, our results
      showed that 1-methyl-4-phenyl-pyridinium ion (MPP+) induced up-regulation of mRNA
      for the Kir6.2 subunit and down-regulation of SUR1. It was further found that
      pretreatment with iptakalim, a novel K(ATP) channel opener, could attenuate
      increased extracellular glutamate level and decreased cell survival in SH-SY5Y
      cell culture after exposure to MPP+. Trans-pyrrolidine-2, 4-dicarboxylic acid (t
      PDC), a glutamate transporter inhibitor, partially blocked the effect of
      iptakalim decreasing extracellular glutamate level. Additionally, iptakalim
      prevented MPP+-induced inhibition of glutamate uptake in primary cultured
      astrocytes. The beneficial effects of iptakalim on glutamate uptake of astrocytes
      were abolished by selective mitochondrial K(ATP) (mitoK(ATP)) channel blocker 5
      HD. These results suggest (i) K(ATP) channel dysfunction may be involved in the
      mechanisms of MPP+-induced cytotoxicity and (ii) iptakalim may modulate glutamate
      transporters and subsequently alleviate the increase of extracellular glutamate
      levels induced by MPP+ through opening mitoK(ATP) channels, thereby protecting SH
      SY5Y cells against MPP+-induced cytotoxicity.

PMID- 16000146
TI  - Expression and function of alpha-adrenoceptors in zebrafish: drug effects, mRNA
      and receptor distributions.
AB  - The alpha2-adrenoceptors are G-protein-coupled receptors that mediate many of the
      physiological effects of norepinephrine and epinephrine. Mammals have three
      subtypes of alpha2-adrenoceptors, alpha2A, alpha2B and alpha2C. Zebrafish, a
      teleost fish used widely as a model organism, has five distinct alpha2
      adrenoceptor genes. The zebrafish has emerged as a powerful tool to study
      development and genetics, with many mutations causing diseases reminiscent of
      human diseases. Three of the zebrafish adra2 genes code for orthologues of the
      mammalian alpha2-adrenoceptors, while two genes code for alpha2Da- and alpha2Db-
      adrenoceptors, representing a duplicated, fourth alpha2-adrenoceptor subtype. The
      three different mammalian alpha2-adrenoceptor subtypes have distinct expression
      patterns in different organs and tissues, and mediate different physiological
      functions. The zebrafish alpha2-adrenergic system, with five different alpha2
      adrenoceptors, appears more complicated. In order to deduce the physiological
      functions of the zebrafish alpha2-adrenoceptors, we localized the expression of
      the five different alpha2-adrenoceptor subtypes using RT-PCR, mRNA in situ
      hybridization, and receptor autoradiography using the radiolabelled alpha2
      adrenoceptor antagonist [ethyl-3H]RS-79948-197. Localization of the alpha2A-,
      alpha2B- and alpha2C-adrenoceptors in zebrafish shows marked conservation when
      compared with mammals. The zebrafish alpha2A, alpha2Da, and alpha2Db each
      partially follow the distribution pattern of the mammalian alpha2A: a possible
      indication of subfunction partitioning between these subtypes. The alpha2
      adrenergic system is functional in zebrafish also in vivo, as demonstrated by
      marked locomotor inhibition, similarly to mammals, and lightening of skin colour
      induced by the specific alpha2-adrenoceptor agonist, dexmedetomidine. Both
      effects were antagonized by the specific alpha2-adrenoceptor antagonist
      atipamezole.

PMID- 16000147
TI  - Distinct patterns of expression and regulation of GABA receptors containing the
      delta subunit in cerebellar granule and hippocampal neurons.
AB  - Neuronal plasticity is achieved by regulation of the expression of genes for
      neurotransmitter receptors such as the type A receptor (GABA(A)R) for gamma
      aminobutyric acid. We now show that two different rat neuronal populations in
      culture manifest distinct patterns of GABA(A)R plasticity in response to
      identical stimuli. Whereas prolonged exposure to ethanol had no effect on
      expression of the delta subunit of GABA(A)Rs at the mRNA or protein level in
      cerebellar granule neurons, it increased the abundance of delta subunit mRNA and
      protein in hippocampal neurons. Subsequent ethanol withdrawal transiently down
      regulated delta subunit expression in cerebellar granule neurons and gradually
      normalized that in hippocampal neurons. These effects of ethanol exposure and
      withdrawal were accompanied by corresponding functional changes in GABA(A)Rs.
      GABA(A)Rs containing the delta subunit were also distributed differentially in
      the cerebellar and hippocampal neurons. These findings reveal complex and
      distinct mechanisms of regulation of the expression of GABA(A)Rs that contain the
      delta subunit in different neuronal types.

PMID- 16000148
TI  - Microglia-specific expression of microsomal prostaglandin E2 synthase-1
      contributes to lipopolysaccharide-induced prostaglandin E2 production.
AB  - Microsomal prostaglandin E2 synthase (mPGES)-1 is an inducible protein recently
      shown to be an important enzyme in inflammatory prostaglandin E2 (PGE2)
      production in some peripheral inflammatory lesions. However, in inflammatory
      sites in the brain, the induction of mPGES-1 is poorly understood. In this study,
      we demonstrated the expression of mPGES-1 in the brain parenchyma in a
      lipopolysaccharide (LPS)-induced inflammation model. A local injection of LPS
      into the rat substantia nigra led to the induction of mPGES-1 in activated
      microglia. In neuron-glial mixed cultures, mPGES-1 was co-induced with
      cyclooxygenase-2 (COX-2) specifically in microglia, but not in astrocytes,
      oligodendrocytes or neurons. In microglia-enriched cultures, the induction of
      mPGES-1, the activity of PGES and the production of PGE2 were preceded by the
      induction of mPGES-1 mRNA and almost completely inhibited by the synthetic
      glucocorticoid dexamethasone. The induction of mPGES-1 and production of PGE2
      were also either attenuated or absent in microglia treated with mPGES-1 antisense
      oligonucleotide or microglia from mPGES-1 knockout (KO) mice, respectively,
      suggesting the necessity of mPGES-1 for microglial PGE2 production. These results
      suggest that the activation of microglia contributes to PGE2 production through
      the concerted de novo synthesis of mPGES-1 and COX-2 at sites of inflammation of
      the brain parenchyma.

PMID- 16000149
TI  - Chronic corticotropin-releasing factor type 1 receptor antagonism with antalarmin
      regulates the dopaminergic system of Fawn-Hooded rats.
AB  - Corticotropin-releasing factor is a neuropeptide associated with the integration
      of physiological and behavioural responses to stress and also in the modulation
      of affective state and drug reward. The selective, centrally acting corticotropin
      releasing factor type 1 receptor antagonist, antalarmin, is a potent anxiolytic
      and reduces volitional ethanol consumption in Fawn-Hooded rats. The efficacy of
      antalarmin to reduce ethanol consumption increased with time, suggestive of
      adaptation to reinforcement processes and goal-directed behaviour. The aim of the
      present study was to examine the effects of chronic antalarmin treatment on
      reward-related regions of Fawn-Hooded rat brain. Bi-daily antalarmin treatment
      (20 mg/kg, i.p.) for 10 days increased tyrosine hydroxylase messenger RNA
      expression throughout the ventral mesencephalon. Following chronic antalarmin the
      density of dopaminergic terminals within the basal ganglia and amygdaloid complex
      were reduced, as was dopamine transporter binding within the striatum. Receptor
      autoradiography indicated an up-regulation of dopamine D2, but no change in D1,
      binding in striatum, and Golgi-Cox analysis of striatal medium spiny neurones
      indicated that chronic antalarmin treatment increased spine density. Thus,
      chronic antalarmin treatment modulates dopaminergic pathways and implies that
      chronic treatment with drugs of this class may ultimately alter postsynaptic
      signaling mechanisms within the basal ganglia.

PMID- 16000150
TI  - Molecular and functional characterization of an Na+-independent choline
      transporter in rat astrocytes.
AB  - In this study, we examined the molecular and functional characterization of
      choline uptake into cultured rat cortical astrocytes. Choline uptake into
      astrocytes showed little dependence on extracellular Na+. Na+-independent choline
      uptake was saturable and mediated by a single transport system, with an apparent
      Michaelis-Menten constant (Km) of 35.7 +/- 4.1 microm and a maximal velocity
      (Vmax) of 49.1 +/- 2.0 pmol/mg protein/min. Choline uptake was significantly
      decreased by acidification of the extracellular medium and by membrane
      depolarization. Na+-independent choline uptake was inhibited by unlabeled
      choline, acetylcholine and the choline analogue hemicholinium-3. The prototypical
      organic cation tetrahexylammonium (TEA), and other n-tetraalkylammonium compounds
      such as tetrabutylammonium (TBA) and tetrahexylammonium (THA), inhibited Na+
      independent choline uptake, and their inhibitory potencies were in the order THA
      > TBA > TEA. Various organic cations, such as 1-methyl-4-tetrahydropyridinium
      (MPP+), clonidine, quinine, quinidine, guanidine, N-methylnicotinamide,
      cimetidine, desipramine, diphenhydramine and verapamil, also interacted with the
      Na+-independent choline transport system. Corticosterone and 17beta-estradiol,
      known inhibitors of organic cation transporter 3 (OCT3), did not cause any
      significant inhibition. However, decynium22, which inhibits OCTs, markedly
      inhibited Na+-independent choline uptake. RT-PCR demonstrated that astrocytes
      expressed low levels of OCT1, OCT2 and OCT3 mRNA, but the functional
      characteristics of choline uptake are very different from the known properties of
      these OCTs. The high-affinity Na+-dependent choline transporter, CHT1, is not
      expressed in astrocytes as evidenced by RT-PCR. Furthermore, mRNA for choline
      transporter-like protein 1 (CTL1), and its splice variants CTL1a and CTL1b, was
      expressed in rat astrocytes, and the inhibition of CTL1 expression by RNA
      interference completely inhibited Na+-independent choline uptake. We conclude
      that rat astrocytes express an intermediate-affinity Na+-independent choline
      transport system. This system seems to occur through a CTL1 and is responsible
      for the uptake of choline and organic cations in these cells.

PMID- 16000151
TI  - Neuronal transmission stimulates the phosphorylation of Kv1.4 channel at Ser229
      through protein kinase A1.
AB  - Phosphorylation of voltage-gated K+ channels (Kv) is involved in regulation of
      neuronal excitability, synaptic plasticity and neuronal survival. Among Kv
      channels expressed in the CNS, Kv1.4 is located in the soma, dendrite and axon
      terminus of neurones in most regions of the brain. Here, we show that Ser229
      found within the highly conserved T1 domain of Kv1.4 in cultured rat cortical
      neurones is phosphorylated by protein kinase A (PKA), as demonstrated by in vitro
      protein kinase assay and Western blotting with a polyclonal antibody specific
      against phosphorylated Ser229. Glutamate, high concentrations of K+ or K+ channel
      blockers known to increase neurotransmission all stimulated the phosphorylation
      of Kv1.4 at Ser229 via N-methyl-D-aspartate (NMDA), but not alpha-amino-3-hydroxy
      5-methylisoxazole-4-proprionic acid (AMPA) receptor, whereas tetradotoxin (TTX),
      known to block neuronal transmission, and depletion of extracellular Ca2+
      inhibited phosphorylation induced by tetraethylammonium (TEA), a non-selective K+
      channel blocker. Mutation of Ser229 to Ala229 enhanced the current density. Taken
      together, elevation of the neuronal transmission stimulates the phosphorylation
      of Kv1.4 at Ser229 via the Ca2+ influx through NMDA receptor. Thus, it is
      possible that neuronal transmission regulates neuronal excitability partially
      through the phosphorylation of Kv1.4S229.

PMID- 16000152
TI  - Involvement of spinal metabotropic glutamate receptor 5 in the development of
      tolerance to morphine-induced antinociception.
AB  - It is well known that prolonged exposure to morphine results in tolerance to
      morphine-induced antinociception. In the present study, we found that either
      intrathecal (i.t.) or subcutaneous (s.c.) injection of the selective metabotropic
      glutamate receptor 5 (mGluR5) antagonist, methyl-6-(phenylethynyl)-pyridine
      hydrochloride (MPEP), attenuated the development of tolerance to morphine-induced
      antinociception. Using the receptor binding assay, we found here that the number
      of mGluR5 in the mouse spinal cord was significantly increased by repeated
      treatment with morphine. Furthermore, repeated treatment with morphine produced a
      significant increase in the level of mGluR5 immunoreactivity in the dorsal horn
      of the mouse spinal cord. Double-labeling experiments showed that the increased
      mGluR5 was predominantly expressed in the neurons and sparsely expressed in the
      processes of astrocytes following repeated treatment with morphine. Consistent
      with these results, the response of Ca2+ to the selective group I mGluR agonist,
      3,5-dihydroxyphenylglycine (DHPG), in cultured spinal cord neurons was potently
      enhanced by 3 days of in vitro treatment with morphine. These findings support
      the idea that the increased mGluR5 following repeated treatment with morphine
      leads to enhanced neuronal excitability and synaptic transmission in the dorsal
      horn of the spinal cord and, in turn, suppresses the morphine-induced
      antinociception in mice.

PMID- 16000153
TI  - Alcohol is a potent stimulant of immature neuronal networks: implications for
      fetal alcohol spectrum disorder.
AB  - Ethanol consumption during development affects the maturation of hippocampal
      circuits by mechanisms that are not fully understood. Ethanol acts as a
      depressant in the mature CNS and it has been assumed that this also applies to
      immature neurons. We investigated whether ethanol targets the neuronal network
      activity that is involved in the refinement of developing hippocampal synapses.
      This activity appears during the growth spurt period in the form of giant
      depolarizing potentials (GDPs). GDPs are generated by the excitatory actions of
      GABA and glutamate via a positive feedback circuit involving pyramidal neurons
      and interneurons. We found that ethanol potently increases GDP frequency in the
      CA3 hippocampal region of slices from neonatal rats. It also increased the
      frequency of GDP-driven Ca2+ transients in pyramidal neurons and increased the
      frequency of GABA(A) receptor-mediated spontaneous postsynaptic currents in CA3
      pyramidal cells and interneurons. The ethanol-induced potentiation of GABAergic
      activity is probably the result of increased quantal GABA release at
      interneuronal synapses but not enhanced neuronal excitability. These findings
      demonstrate that ethanol is a potent stimulant of developing neuronal circuits,
      which might contribute to the abnormal hippocampal development associated with
      fetal alcohol syndrome and alcohol-related neurodevelopmental disorders.

PMID- 16000155
TI  - Somatostatin and the somatostatin receptor 2 are reciprocally controlled by
      calcineurin during cerebellar granule cell maturation.
AB  - Activity-dependent Ca2+ influx into neurones and the subsequent changes in gene
      expression are thought to be important in shaping neuronal development. In this
      study, we investigated whether an important mediator of neuronal migration,
      somatostatin (Srif), alongside its receptors, is controlled in this manner in
      cerebellar granule cells. We show that Ca2+ influx increases the expression of
      somatostatin mRNA (srif), while somatostatin receptor 2 (sst2) mRNA expression is
      decreased. Both genes appear to be regulated independently of each other and in a
      calcineurin-dependent manner that does not depend on either the ERK1/2 MAP kinase
      or the cAMP/CREB pathway. Nonetheless, a second pathway is required to induce
      changes in srif and sst2 expression, since constitutively active calcineurin
      alone is not sufficient to induce these changes. Furthermore, calcineurin
      activation reciprocally regulates the expression of brain-derived neurotrophic
      factor, bdnf, and its receptor trkb, which have also been shown to play a role in
      neuronal migration. Finally, calcineurin appears to control the expression of the
      neuronal marker transient axonal glycoprotein 1, tag-1, thereby strongly
      suggesting that calcineurin activation in vivo occurs during the late stages of
      neuronal migration, possibly during synaptogenesis with mossy fibres. We
      therefore propose that calcineurin might play an important role as a switch
      between transcriptional programs during neuronal development.

PMID- 16000154
TI  - Hypoxia-activated metabolic pathway stimulates phosphorylation of p300 and CBP in
      oxygen-sensitive cells.
AB  - Transcription co-activators and histone acetyltransferases, p300 and cyclic AMP
      responsive element-binding protein-binding protein (CBP), participate in hypoxic
      activation of hypoxia-inducible genes. Here, we show that exposure of PC12 and
      cells to 1-10% oxygen results in hyperphosphorylation of p300/CBP. This response
      is fast, long lasting and specific for hypoxia, but not for hypoxia-mimicking
      agents such as desferioxamine or Co2+ ions. It is also cell-type specific and
      occurs in pheochromocytoma PC12 cells and the carotid body of rats but not in
      hepatoblastoma cells. The p300 hyperphosphorylation specifically depends on the
      release of intracellular calcium from inositol 1,4,5-triphosphate (IP3)-sensitive
      stores. However, it is not inhibited by pharmacological inhibitors of any of the
      kinases traditionally known to be directly or indirectly calcium regulated. On
      the other hand, p300 hyperphosphorylation is inhibited by several different
      inhibitors of the glucose metabolic pathway from generation of NADH by
      glyceraldehyde 3-phosphate dehydrogenase, through the transfer of NADH through
      the glycerol phosphate shuttle to ubiquinone and complex III of the mitochondrial
      respiratory chain. Inhibition of IP3-sensitive calcium stores decreases
      generation of ATP, and this inhibition is significantly stronger in hypoxia than
      in normoxia. We propose that the NADH glycerol phosphate shuttle participates in
      generating a pool of ATP that serves either as a co-factor or a modulator of the
      kinases involved in the phosphorylation of p300/CBP during hypoxia.

PMID- 16000156
TI  - Methadone increases intracellular calcium in SH-SY5Y and SH-EP1-halpha7 cells by
      activating neuronal nicotinic acetylcholine receptors.
AB  - (-)-Methadone acts as an agonist at opioid receptors. Both (+)- and (-)
      enantiomers of methadone have been suggested to be potent non-competitive
      antagonists of alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs).
      In the present study, we have examined interactions of methadone with nAChRs by
      using receptor binding assays, patch-clamp recording and calcium fluorometry
      imaging with SH-SY5Y cells naturally expressing alpha7 and alpha3* nAChR subtypes
      and SH-EP1-halpha7 cells heterologously expressing human alpha7 nAChRs. Methadone
      potently inhibited binding of [3H]methyllycaconitine to alpha7 nAChRs and that of
      [3H]epibatidine to alpha3* nAChRs. Methadone pretreatment induced up-regulation
      of epibatidine binding sites in SH-SY5Y cells. Using whole-cell patch-clamp
      recording, both isomers of methadone activated cation currents via mecamylamine
      sensitive nAChRs in SH-SY5Y cells. Nicotine and both (+)- and (-)-methadone
      evoked increases in [Ca2+]i in both fluo-3AM loaded cell lines, and these effects
      were blocked by mecamylamine and by the alpha7 selective antagonist
      methyllycaconitine, suggesting effects of methadone as alpha7-nAChR agonist.
      Sensitivity of sustained nicotine and methadone effects to blockade by CdCl2,
      ryanodine and xestospongin-c implicates voltage-operated Ca2+ channels and
      intracellular Ca2+ stores as downstream modulators of elevated [Ca2+]i.
      Collectively, our results suggest that methadone engages in complex and
      potentially pharmacologically significant interactions with nAChRs.

PMID- 16000157
TI  - PERK is responsible for the increased phosphorylation of eIF2alpha and the severe
      inhibition of protein synthesis after transient global brain ischemia.
AB  - Reperfusion after global brain ischemia results initially in a widespread
      suppression of protein synthesis in neurons that is due to inhibition of
      translation initiation as a result of the phosphorylation of the alpha-subunit of
      eukaryotic initiation factor 2 (eIF2). To address the role of the eIF2alpha
      kinase RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) in
      the reperfused brain, transgenic mice with a targeted disruption of the Perk gene
      were subjected to 20 min of forebrain ischemia followed by 10 min of reperfusion.
      In wild-type mice, phosphorylated eIF2alpha was detected in the non-ischemic
      brain and its levels were elevated threefold after 10 min of reperfusion.
      Conversely, there was no phosphorylated eIF2alpha detected in the non-ischemic
      transgenic mice and there was no sizeable rise in phosphorylated eIF2alpha levels
      in the forebrain after ischemia and reperfusion. Moreover, there was a
      substantial rescue of protein translation in the reperfused transgenic mice.
      Neither group showed any change in total eIF2alpha, phosphorylated eukaryotic
      elongation factor 2 or total eukaryotic elongation factor 2 levels. These data
      demonstrate that PERK is responsible for the large increase in phosphorylated
      eIF2alpha and the suppression of translation early in reperfusion after transient
      global brain ischemia.

PMID- 16000159
TI  - Blockade of L-type voltage-gated Ca channel inhibits ischemia-induced
      neurogenesis by down-regulating iNOS expression in adult mouse.
AB  - Neurogenesis in the adult mammalian hippocampus may contribute to repairing the
      brain after injury. The signals that regulate neurogenesis in the dentate gyrus
      following ischemic stroke insult are not well known. We have previously reported
      that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia
      stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice
      subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly
      increased the number of new neurons and up-regulated iNOS expression in the
      dentate gyrus. Blockade of the L-type voltage-gated Ca(2+) channel (L-VGCC)
      prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and
      down-regulated iNOS expression in the dentate gyrus after cerebral ischemia. This
      study suggests that Ca(2+) influx through L-VGCC is involved in ischemia-induced
      neurogenesis by up-regulating iNOS expression.

PMID- 16000160
TI  - L3/Lhx8 is involved in the determination of cholinergic or GABAergic cell fate.
AB  - The LIM homeobox family of transcription factors is involved in many processes
      during the development of the mammalian central nerves system. L3, also called
      Lhx8 (L3/Lhx8), is a recently identified member of the LIM homeobox gene family
      and is selectively expressed in the medial ganglionic eminence (MGE). Our
      previous study demonstrated that L3/Lhx8-null mice specifically lacked
      cholinergic neurons in the basal forebrain. In this study, we reduced L3/Lhx8
      function in the murine neuroblastoma cell line, Neuro2a (N2a), using L3/Lhx8
      targeted small interfering RNA (siRNA) produced by H1.2 promoter-driven vector.
      The levels of cholinergic markers per cell were diminished without a reduction in
      the number of marker-positive cells. Intriguingly, GABAergic marker expression
      and the number of GABAergic cells were dramatically increased in the
      differentiating L3/Lhx8-knockdown N2a. These results suggest the possibility that
      L3/Lhx8 is involved in the determination of transmitter phenotypes (GABAergic or
      cholinergic cell fate) in a population of neurons during basal forebrain
      development.

PMID- 16000162
TI  - RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated
      protein kinase activation.
AB  - A yeast two-hybrid screen using the last 28 amino acids of the cytoplasmic domain
      of the neural cell adhesion molecule L1 identified RanBPM as an L1-interacting
      protein. RanBPM associates with L1 in vivo and the N-terminal region of RanBPM (N
      RanBPM), containing the SPRY domain, is sufficient for the interaction with L1 in
      a glutathione S-transferase pull-down assay. L1 antibody patching dramatically
      changes the subcellular localization of N-RanBPM in transfected COS cells.
      Overexpression of N-RanBPM in COS cells reduces L1-triggered extracellular signal
      regulated kinase 1/2 activation by 50% and overexpression of N-RanBPM in primary
      neurons inhibits L1-mediated neurite outgrowth and branching. These data suggest
      that RanBPM is an adaptor protein that links L1 to the extracellular signal
      regulated kinase/MAPK pathway.

PMID- 16000163
TI  - Differential effects of l-DOPA on monoamine metabolism, cell survival and
      glutathione production in midbrain neuronal-enriched cultures from parkin
      knockout and wild-type mice.
AB  - l-DOPA is the most effective treatment for Parkinson's disease but in isolated
      neuronal cultures it is neurotoxic for dopamine (DA) neurones. Experiments in
      vivo and clinical studies have failed to show toxicity of l-DOPA in animals or
      patients but that does not exclude the possibility of a toxic effect of l-DOPA on
      patients with certain genetic risk factors. Mutations of the parkin gene are the
      most frequent cause of hereditary parkinsonism. Parkin null mice have a mild
      phenotype that could be modified by different neurotoxins. The aim of this study
      was to investigate whether the toxic effects of l-DOPA on DA neurones are
      amplified in parkin null mice. We have measured the effects of l-DOPA on cell
      viability, tyrosine hydroxylase (TH) expression, DA metabolism and glutathione
      levels of parkin knockout (PK-KO) midbrain cultures. Neuronal-enriched cultures
      from PK-KO mice have similar proportions of the different cell types with the
      exception of a significant increment of microglial cells. l-DOPA (400 microm for
      24 h) reduced the number of TH-immunoreactive cells to 50% of baseline and
      increased twofold the percentage of apoptotic cells in cultures of wild-type (WT)
      animals. The PK-KO mice, however, are not only resistant to the l-DOPA-induced
      pro-apoptotic effects but they have an increased number of TH-immunoreactive
      neurones after treatment with l-DOPA, suggesting that l-DOPA is toxic for
      neurones of WT mice but not those of parkin null mice. MAPK and
      phosphatidylinositol-3 kinase signalling pathways are not involved in the
      differential l-DOPA effects in WT and PK-KO cultures. Intracellular levels of l
      DOPA were not different in WT and parkin null mice but the intracellular and
      extracellular levels of DA and 3-4-dihydroxyphenylacetic acid, however, were
      significantly increased in parkin null animals. Furthermore, monoamine oxidase
      activity was significantly increased in parkin null mice, suggesting that these
      animals have an increased metabolism of DA. The levels of glutathione were
      further increased in parkin null mice than in controls both with and without
      treatment with l-DOPA, suggesting that a compensatory mechanism may protect DA
      neurones from neuronal death. This study opens new avenues for understanding the
      mechanisms of action of l-DOPA on DA neurones in patients with Park-2 mutations.

PMID- 16000164
TI  - Activation of NMDA receptors induces protein kinase A-mediated phosphorylation
      and degradation of matrin 3. Blocking these effects prevents NMDA-induced
      neuronal death.
AB  - Activation of NMDA receptors leads to activation of cAMP-dependent protein kinase
      (PKA). The main substrates phosphorylated by PKA following NMDA receptor
      activation remain unidentified. The aim of this work was to identify a major
      substrate phosphorylated by PKA following NMDA receptor activation in cerebellar
      neurones in culture, and to assess whether this phosphorylation may be involved
      in neuronal death induced by excessive NMDA receptor activation. The main PKA
      substrate following NMDA receptor activation was identified by MALDI-TOFF
      fingerprinting as the nuclear protein, matrin 3. PKA-mediated phosphorylation of
      matrin 3 is followed by its degradation. NMDA receptor activation in rat brain in
      vivo by ammonia injection also induced PKA-mediated matrin 3 phosphorylation and
      degradation in brain cell nuclei. Blocking NMDA receptors in brain in vivo with
      MK-801 reduced basal phosphorylation of matrin 3, suggesting that it is modulated
      by NMDA receptors. Inhibition of PKA with H-89 prevents NMDA-induced
      phosphorylation and degradation of matrin 3 as well as neuronal death. These
      results suggest that PKA-mediated phosphorylation of matrin 3 may serve as a
      rapid way of transferring information from synapses containing NMDA receptors to
      neuronal nuclei under physiological conditions, and may contribute to neuronal
      death under pathological conditions.

PMID- 16000165
TI  - The excitoprotective effect of N-methyl-D-aspartate receptors is mediated by a
      brain-derived neurotrophic factor autocrine loop in cultured hippocampal neurons.
AB  - The neuroprotective effect and molecular mechanisms underlying preconditioning
      with N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons have not been
      described. Pre-incubation with subtoxic concentrations of the endogenous
      neurotransmitter glutamate protects vulnerable neurons against NMDA receptor
      mediated excitotoxicity. As a result of physiological preconditioning, NMDA
      significantly antagonizes the neurotoxicity resulting from subsequent exposure to
      an excitotoxic concentration of glutamate. The protective effect of glutamate or
      NMDA is time- and concentration-dependent, suggesting that sufficient agonist and
      time are required to establish an intracellular neuroprotective state. In these
      cells, the TrkB ligand, brain-derived neurotrophic factor (BDNF) attenuates
      glutamate toxicity. Therefore, we tested the hypothesis that NMDA protects
      neurons via a BDNF-dependent mechanism. Exposure of hippocampal cultures to a
      neuroprotective concentration of NMDA (50 microM) evoked the release of BDNF
      within 2 min without attendant changes in BDNF protein or gene expression. The
      accumulated increase of BDNF in the medium is followed by an increase in the
      phosphorylation (activation) of TrkB receptors and a later increase in exon 4
      specific BDNF mRNA. The neuroprotective effect of NMDA was attenuated by pre
      incubation with a BDNF-blocking antibody and TrkB-IgG, a fusion protein known to
      inhibit the activity of extracellular BDNF, suggesting that BDNF plays a major
      role in NMDA-mediated survival. These results demonstrate that low level
      stimulation of NMDA receptors protect neurons against glutamate excitotoxicity
      via a BDNF autocrine loop in hippocampal neurons and suggest that activation of
      neurotrophin signaling pathways plays a key role in the neuroprotection of NMDA.

PMID- 16000166
TI  - Probable neuroimmunological link between Toxoplasma and cytomegalovirus
      infections and personality changes in the human host.
AB  - BACKGROUND: Recently, a negative association between Toxoplasma-infection and
      novelty seeking was reported. The authors suggested that changes of personality
      trait were caused by manipulation activity of the parasite, aimed at increasing
      the probability of transmission of the parasite from an intermediate to a
      definitive host. They also suggested that low novelty seeking indicated an
      increased level of the neurotransmitter dopamine in the brain of infected
      subjects, a phenomenon already observed in experimentally infected rodents.
      However, the changes in personality can also be just a byproduct of any
      neurotropic infection. Moreover, the association between a personality trait and
      the toxoplasmosis can even be caused by an independent correlation of both the
      probability of Toxoplasma-infection and the personality trait with the third
      factor, namely with the size of living place of a subject. To test these two
      alternative hypotheses, we studied the influence of another neurotropic pathogen,
      the cytomegalovirus, on the personality of infected subjects, and reanalyzed the
      original data after the effect of the potential confounder, the size of living
      place, was controlled. METHODS: In the case-control study, 533 conscripts were
      tested for toxoplasmosis and presence of anti-cytomegalovirus antibodies and
      their novelty seeking was examined with Cloninger's TCI questionnaire. Possible
      association between the two infections and TCI dimensions was analyzed. RESULTS:
      The decrease of novelty seeking is associated also with cytomegalovirus
      infection. After the size of living place was controlled, the effect of
      toxoplasmosis on novelty seeking increased. Significant difference in novelty
      seeking was observed only in the largest city, Prague. CONCLUSION: Toxoplasma and
      cytomegalovirus probably induce a decrease of novelty seeking. As the
      cytomegalovirus spreads in population by direct contact (not by predation as with
      Toxoplasma), the observed changes are the byproduct of brain infections rather
      than the result of manipulation activity of a parasite. Four independent lines of
      indirect evidence, namely direct measurement of neurotransmitter concentration in
      mice, the nature of behavioral changes in rodents, the nature of personality
      changes in humans, and the observed association between schizophrenia and
      toxoplasmosis, suggest that the changes of dopamine concentration in brain could
      play a role in behavioral changes of infected hosts.

PMID- 16000167
TI  - Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non
      small cell lung cancer.
AB  - BACKGROUND: Combined chemoradiotherapy (CRT) is the treatment of choice for stage
      III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven
      to be a potent radiosensitizer. Twenty-two consecutive patients were treated with
      concurrent CRT to demonstrate the tolerability and efficacy of low dose G given
      weekly as radiosensitizer in stage III NSCLC. METHODS: Patients with KPS >or=70,
      adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were
      included. Eighteen patients had received prior induction chemotherapy (CT). G (75
      mg/m2/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours
      later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary
      toxicity was evaluated with computed tomography scans in 6 weeks. RESULTS: Median
      age was 60 years (range, 48-75), median follow-up was 15 months (range, 2-40).
      Sixty-eight percent of patients were male and median KPS score was 90. Conformal
      3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks
      (range 1-9). Twelve patients (54.6%) received all planned CT. G was stopped
      because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had
      radiation pneumonitis. Twenty patients were evaluated for overall response, 1
      patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall
      survival (OS) was 14 +/- 5 months (95% CI 3-25). One- and 2-year OS rates were
      55% and 38%. Sixteen patients died of disease-related events (6 with progression
      of primary tumor, 8 due to metastatic disease), 2 patients died of other causes.
      One- and 2-year progression-free survival and local control rates were 56%, 27%
      and 79%, 51%, respectively. CONCLUSION: G might be used as radiosensitizer for
      patients with stage III NSCLC who could not receive full doses CT with concurrent
      RT.

PMID- 16000168
TI  - Positional and functional mapping of a neuroblastoma differentiation gene on
      chromosome 11.
AB  - BACKGROUND: Loss of chromosome 11q defines a subset of high-stage aggressive
      neuroblastomas. Deletions are typically large and mapping efforts have thus far
      not lead to a well defined consensus region, which hampers the identification of
      positional candidate tumour suppressor genes. In a previous study, functional
      evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained
      through microcell mediated chromosome transfer, indicated by differentiation of
      neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11.
      Interestingly, some of these microcell hybrid clones were shown to harbour
      deletions in the transferred chromosome 11. We decided to further exploit this
      model system as a means to identify candidate tumour suppressor or
      differentiation genes located on chromosome 11. RESULTS: In a first step, we
      performed high-resolution array CGH DNA copy-number analysis in order to evaluate
      the chromosome 11 status in the hybrids. Several deletions in both parental and
      transferred chromosomes in the investigated microcell hybrids were observed.
      Subsequent correlation of these deletion events with the observed morphological
      changes lead to the delineation of three putative regions on chromosome 11:
      11q25, 11p13-->11p15.1 and 11p15.3, that may harbour the responsible
      differentiation gene. CONCLUSION: Using an available model system, we were able
      to put forward some candidate regions that may be involved in neuroblastoma.
      Additional studies will be required to clarify the putative role of the genes
      located in these chromosomal segments in the observed differentiation phenotype
      specifically or in neuroblastoma pathogenesis in general.

PMID- 16000169
TI  - An in vivo analysis of the localisation and interactions of human p66 DNA
      polymerase delta subunit.
AB  - BACKGROUND: DNA polymerase delta is essential for eukaryotic DNA replication and
      also plays a role in DNA repair. The processivity of this polymerase complex is
      dependent upon its interaction with the sliding clamp PCNA and the polymerase
      PCNA interaction is largely mediated through the p66 polymerase subunit. We have
      analysed the interactions of the human p66 DNA polymerase delta subunit with PCNA
      and with components of the DNA polymerase delta complex in vivo. RESULTS: Using
      the two-hybrid system, we have mapped the interaction domains for binding to the
      p50 polymerase delta subunit and with PCNA to the N-terminus and the C-terminus
      of p66, respectively. Co-immunoprecipitation experiments confirm that these
      interaction domains are functional in vivo. Expression of EGFP-p66 shows that it
      is a nuclear protein which co-localises with PCNA throughout the cell cycle. p66
      is localised to sites of DNA replication during S phase and to repair foci
      following DNA damage. We have identified a functional nuclear localisation
      sequence and shown that localisation to replication foci is not dependent upon
      active nuclear import. Sub-domains of p66 act as dominant negative suppressors of
      colony formation, suggesting that p66 forms an essential structural link between
      the p50 subunit and PCNA. Analysis of the C-terminal PCNA binding motif shows
      that deletion of the QVSITGFF core motif results in a reduced affinity for PCNA,
      while deletion of a further 20 amino acids completely abolishes the interaction.
      A reduced affinity for PCNA correlates with reduced targeting to replication
      foci. We have confirmed the p66-PCNA interaction in vivo using fluorescence
      resonance energy transfer (FRET) techniques. CONCLUSION: We have defined the
      regions of p66 required for its interaction with PCNA and the p50 polymerase
      subunit. We demonstrate a functional link between PCNA interaction and
      localisation to replication foci and show that there is a direct interaction
      between p66 and PCNA in living cells during DNA replication. The dominant
      negative effect upon growth resulting from expression of p66 sub-domains confirms
      that the p66-PCNA interaction is essential in vivo.

PMID- 16000170
TI  - Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients
      with lung cancer.
AB  - BACKGROUND: Medical oncologists continue to use performance status as a proxy for
      quality of life (QOL) measures, as completion of QOL instruments is perceived as
      time consuming, may measure aspects of QOL not affected by cancer therapy, and
      interpretation may be unclear. The pulse oximeter is widely used in clinical
      practice to predict cardiopulmonary morbidity after lung resection in cancer
      patients, but little is known on its role outside the surgical setting. We
      evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute
      to the evaluation of lung cancer patients who received standard anticancer
      therapy. METHODS: We enrolled forty-one consecutive, newly diagnosed, patients
      with locally advanced or metastatic lung cancer in this study. We developed a
      survival model with the variables gender, age, histology, clinical stage,
      Karnofsky performance status, wasting, LCSS symptom scores, average symptom
      burden index, and pulse oximetry (SpO2). RESULTS: Patient and observer-rated
      scores were correlated, except for the fatigue subscale. The median SpO2 was 95%
      (range: 86 to 98), was unrelated to symptom scores, and was weakly correlated
      with observer cough scores. In a multivariate survival model, SpO2 > 90% and
      patient scores on the LCSS appetite and fatigue subscales were independent
      predictors of survival. CONCLUSION: LCSS fatigue and appetite rating, and pulse
      oximetry should be studied further as prognostic factors in lung cancer patients.

PMID- 16000171
TI  - Computer-aided dermoscopy for diagnosis of melanoma.
AB  - BACKGROUND: Computer-aided dermoscopy using artificial neural networks has been
      reported to be an accurate tool for the evaluation of pigmented skin lesions. We
      set out to determine the sensitivity and specificity of a computer-aided
      dermoscopy system for diagnosis of melanoma in Iranian patients. METHODS: We
      studied 122 pigmented skin lesions which were referred for diagnostic evaluation
      or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes
      and all of their clinical diagnostic considerations were recorded. The lesions
      were analyzed using a microDERM dermoscopy unit. The output value of the software
      for each lesion was a score between 0 and 10. All of the lesions were excised and
      examined histologically. RESULTS: Histopathological examination revealed melanoma
      in six lesions. Considering only the most likely clinical diagnosis, sensitivity
      and specificity of clinical examination for diagnosis of melanoma were 83% and
      96%, respectively. Considering all clinical diagnostic considerations, the
      sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88
      for dermoscopy score, the sensitivity and specificity of the score for diagnosis
      of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34,
      the sensitivity and specificity were 100% and 90%. CONCLUSION: The diagnostic
      accuracy of the dermoscopy system was at the level of clinical examination by
      dermatologists with naked eyes. This system may represent a useful tool for
      screening of melanoma, particularly at centers not experienced in the field of
      pigmented skin lesions.

PMID- 16000172
TI  - Further evidence for increased macrophage migration inhibitory factor expression
      in prostate cancer.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine associated
      with prostate cancer, based on histologic evidence and circulating (serum)
      levels. Recent studies from another laboratory failed to document these results.
      This study's aims were to extend and confirm our previous data, as well as to
      define possible mechanisms for the discrepant results. Additional aims were to
      examine MIF expression, as well as the location of MIF's receptor, CD74, in human
      prostatic adenocarcinoma compared to matched benign prostate. METHODS: MIF
      amounts were determined in random serum samples remaining following routine PSA
      screening by ELISA. Native, denaturing and reducing polyacrylamide gels and
      Western blot analyses determined the MIF form in serum. Prostate tissue arrays
      were processed for MIF in situ hybridization and immunohistochemistry for MIF and
      CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3
      cells was detected by Western blot analysis. RESULTS: Median serum MIF amounts
      were significantly elevated in prostate cancer patients (5.87 +/- 3.91 ng/ml; +/-
      interquartile range; n = 115) compared with patients with no documented diagnosis
      of prostate cancer (2.19 +/- 2.65 ng/ml; n = 158). ELISA diluent reagents that
      included bovine serum albumin (BSA) significantly reduced MIF serum detection (p
      < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but
      cancer showed statistically greater MIF expression. MIF and its receptor (CD74)
      were localized to prostatic epithelium. Increased secreted MIF was detected in
      culture medium from prostate cancer cell lines (LNCaP and PC-3). CONCLUSION:
      Increased serum MIF was associated with prostate cancer. Diluent reagents that
      included BSA resulted in MIF serum immunoassay interference. In addition,
      significant amounts of complexed MIF (180 kDa under denaturing conditions by
      Western blot) found in the serum do not bind to the MIF capture antibody.
      Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared
      to benign tissue from matched samples, supporting our earlier finding of
      increased MIF gene expression in prostate cancer.

PMID- 16000173
TI  - [ISRCTN 16558617] A randomized, controlled trial of spinal endoscopic
      adhesiolysis in chronic refractory low back and lower extremity pain.
AB  - BACKGROUND: Postoperative epidural fibrosis may contribute to between 5% to 60%
      of the poor surgical outcomes following decompressive surgery. Correlations have
      been reported between epidural scarring and radicular pain, poor surgical
      outcomes, and a lack of any form of surgical treatment. The use of spinal
      endoscopic adhesiolysis in recent years in the management of chronic refractory
      low back and lower extremity pain has been described. METHODS: A prospective,
      randomized, double-blind trial was conducted to determine the outcome of spinal
      endoscopic adhesiolysis to reduce pain and improve function and psychological
      status in patients with chronic refractory low back and lower extremity pain. A
      total of 83 patients were evaluated, with 33 patients in Group I and 50 patients
      in Group II. Group I served as the control, with endoscopy into the sacral level
      without adhesiolysis, followed by injection of local anesthetic and steroid.
      Group II received spinal endoscopic adhesiolysis, followed by injection of local
      anesthetic and steroid. RESULTS: Among the 50 patients in the treatment group
      receiving spinal endoscopic adhesiolysis, significant improvement without adverse
      effects was shown in 80% at 3 months, 56% at 6 months, and 48% at 12 months. The
      control group showed improvement in 33% of the patients at one month and none
      thereafter. Based on the definition that less than 6 months of relief is
      considered short-term and longer than 6 months of relief is considered long-term,
      a significant number of patients obtained long-term relief with improvement in
      pain, functional status, and psychological status. CONCLUSION: Spinal endoscopic
      adhesiolysis with targeted delivery of local anesthetic and steroid is an
      effective treatment in a significant number of patients with chronic low back and
      lower extremity pain without major adverse effects.

PMID- 16000174
TI  - Small philanthropy and big science: the RETROVIROLOGY prize and Stephen P. Goff.
AB  - Stephen P. Goff wins the 2005 RETROVIROLOGY prize.

PMID- 16000175
TI  - Chiropractic as spine care: a model for the profession.
AB  - BACKGROUND: More than 100 years after its inception the chiropractic profession
      has failed to define itself in a way that is understandable, credible and
      scientifically coherent. This failure has prevented the profession from
      establishing its cultural authority over any specific domain of health care.
      OBJECTIVE: To present a model for the chiropractic profession to establish
      cultural authority and increase market share of the public seeking chiropractic
      care. DISCUSSION: The continued failure by the chiropractic profession to remedy
      this state of affairs will pose a distinct threat to the future viability of the
      profession. Three specific characteristics of the profession are identified as
      impediments to the creation of a credible definition of chiropractic: Departures
      from accepted standards of professional ethics; reliance upon obsolete principles
      of chiropractic philosophy; and the promotion of chiropractors as primary care
      providers. A chiropractic professional identity should be based on spinal care as
      the defining clinical purpose of chiropractic, chiropractic as an integrated part
      of the healthcare mainstream, the rigorous implementation of accepted standards
      of professional ethics, chiropractors as portal-of-entry providers, the
      acceptance and promotion of evidence-based health care, and a conservative
      clinical approach. CONCLUSION: This paper presents the spine care model as a
      means of developing chiropractic cultural authority and relevancy. The model is
      based on principles that would help integrate chiropractic care into the
      mainstream delivery system while still retaining self-identity for the
      profession.

PMID- 16000176
TI  - A novel Geobacteraceae-specific outer membrane protein J (OmpJ) is essential for
      electron transport to Fe(III) and Mn(IV) oxides in Geobacter sulfurreducens.
AB  - BACKGROUND: Metal reduction is thought to take place at or near the bacterial
      outer membrane and, thus, outer membrane proteins in the model dissimilatory
      metal-reducing organism Geobacter sulfurreducens are of interest to understand
      the mechanisms of Fe(III) reduction in the Geobacter species that are the
      predominant Fe(III) reducers in many environments. Previous studies have
      implicated periplasmic and outer membrane cytochromes in electron transfer to
      metals. Here we show that the most abundant outer membrane protein of G.
      sulfurreducens, OmpJ, is not a cytochrome yet it is required for metal
      respiration. RESULTS: When outer membrane proteins of G. sulfurreducens were
      separated via SDS-PAGE, one protein, designated OmpJ (outer membrane protein J),
      was particularly abundant. The encoding gene, which was identified from mass
      spectrometry analysis of peptide fragments, is present in other Geobacteraceae,
      but not in organisms outside this family. The predicted localization and
      structure of the OmpJ protein suggested that it was a porin. Deletion of the ompJ
      gene in G. sulfurreducens produced a strain that grew as well as the wild-type
      strain with fumarate as the electron acceptor but could not grow with metals,
      such as soluble or insoluble Fe(III) and insoluble Mn(IV) oxide, as the electron
      acceptor. The heme c content in the mutant strain was ca. 50% of the wild-type
      and there was a widespread loss of multiple cytochromes from soluble and membrane
      fractions. Transmission electron microscopy analyses of mutant cells revealed an
      unusually enlarged periplasm, which is likely to trigger extracytoplasmic stress
      response mechanisms leading to the degradation of periplasmic and/or outer
      membrane proteins, such as cytochromes, required for metal reduction. Thus, the
      loss of the capacity for extracellular electron transport in the mutant could be
      due to the missing c-type cytochromes, or some more direct, but as yet unknown,
      role of OmpJ in metal reduction. CONCLUSION: OmpJ is a putative porin found in
      the outer membrane of the model metal reducer G. sulfurreducens that is required
      for respiration of extracellular electron acceptors such as soluble and insoluble
      metals. The effect of OmpJ in extracellular electron transfer is indirect, as
      OmpJ is required to keep the integrity of the periplasmic space necessary for
      proper folding and functioning of periplasmic and outer membrane electron
      transport components. The exclusive presence of ompJ in members of the
      Geobacteraceae family as well as its role in metal reduction suggest that the
      ompJ sequence may be useful in tracking the growth or activity of Geobacteraceae
      in sedimentary environments.

PMID- 16000177
TI  - Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early
      pregnancy.
AB  - BACKGROUND: Bacterial vaginosis (BV) is the single most common vaginal infection
      in women of childbearing age and associated with a sizeable infectious disease
      burden among both non-pregnant and pregnant women, including a significantly
      elevated risk of adverse pregnancy outcome. Overall, little progress has been
      made in identifying causal factors involved in BV acquisition and persistence. We
      sought to evaluate maternal iron status in early pregnancy as a putative risk
      factor for BV, considering that micronutrients, and iron deficiency in
      particular, affect the host response against bacterial colonization, even in the
      setting of mild micronutrient deficiencies. METHODS: In a nested case-control
      study, we compared maternal iron status at entry to prenatal care (mean
      gestational age 9.2 +/- 2.6 weeks) between eighty women with healthy vaginal
      microflora and eighteen women with vaginosis-like microflora. Vaginal microflora
      status was assessed by assigning a modified Nugent score to a Gram-stained
      vaginal smear. Maternal iron status was assayed by an array of conventional
      erythrocyte and serum indicators for iron status assessment, but also by more
      sensitive and more specific indicators of iron deficiency, including soluble
      transferrin receptors (sTfR) as an accurate measure of cellular and tissue iron
      deficiency and the iron deficiency log10[sTfR/ferritin] index as the presently
      most accurate measure of body storage iron available. RESULTS: We found no
      statistically significant correlation between vaginal microflora status and
      routinely assessed iron parameters. In contrast, a highly significant difference
      between the healthy and vaginosis-like microflora groups of women was shown in
      mean values of sTfR concentrations (1.15 +/- 0.30 mg/L versus 1.37 +/- 0.38 mg/L,
      p = 0.008) and in mean iron deficiency log10[sTfR/ferritin] index values (1.57 +/
      0.30 versus 1.08 +/- 0.56, p = 0.003), indicating a strong association between
      iron deficiency and vaginosis-like microflora. An sTfR concentration > 1.45 mg/L
      was associated with a 3-fold increased risk (95%CI: 1.4-6.7) of vaginosis-like
      microflora and after controlling for maternal age, gestational length, body mass,
      parity, and smoking habits with an adjusted odds ratio of 4.5 (95%CI: 1.4-14.2).
      CONCLUSION: We conclude that subclinical iron deficiency, presumably resulting
      from inadequate preconceptional iron supplies, is strongly and independently
      associated with vaginosis-like microflora during early pregnancy.

PMID- 16000178
TI  - Assessment of an electronic voting system within the tutorial setting: a
      randomised controlled trial [ISRCTN54535861].
AB  - BACKGROUND: Electronic voting systems have been used in various educational
      settings with little measurement of the educational impact on students. The goal
      of this study was to measure the effects of the inclusion of an electronic voting
      system within a small group tutorial. METHOD: A prospective randomised controlled
      trial was run at the Royal Adelaide Hospital, a teaching hospital in Adelaide,
      Australia. 102 students in their first clinical year of medical school
      participated in the study where an electronic voting system was introduced as a
      teaching aid into a standard tutorial. Long-term retention of knowledge and
      understanding of the topics discussed in the tutorials was measured and student
      response to the introduction of the electronic voting system was assessed.
      RESULTS: Students using the electronic voting system had improved long-term
      retention of understanding of material taught in the tutorial. Students had a
      positive response to the use of this teaching aid. CONCLUSION: Electronic voting
      systems can provide a stimulating learning environment for students and in a
      small group tutorial may improve educational outcomes.

PMID- 16000193
TI  - ?

PMID- 16000179
TI  - Prevalence of thyroid nodules in an occupationally radiation exposed group: a
      cross sectional study in an area with mild iodine deficiency.
AB  - BACKGROUND: Thyroid nodules and thyroid cancer occur more frequently in people
      exposed to radiation for therapeutic purposes, and to nuclear fallout.
      Furthermore, it is known that a moderate degree of iodine deficiency may be
      responsible for an increased prevalence of thyroid nodules, while it is suspected
      that radiation exposure could induce changes in thyroid autoimmunity. The iodine
      intake of people resident in Bari, S. Italy, is mildly deficient, which could be
      presumed to cause a higher prevalence of thyroid pathology. This study was
      conducted to evaluate the prevalence of thyroid nodules in a population
      occupationally exposed to radiation, in an area of mild iodine deficiency.
      METHODS: A cross-sectional study was designed to evaluate the prevalence of
      thyroid nodules in radiation exposed workers, compared with a stratified sample
      of non exposed workers. After giving written consent to participate in the study,
      all the recruited subjects (304 exposed and 419 non exposed volunteers) were
      interviewed to fill in an anamnestic questionnaire, and underwent a physical
      examination, ultrasound thyroid scan, serum determinations of fT3, fT4 and TSH,
      fine needle aspiration biopsy. The sample was subdivided into one group exposed
      to a determined quantity of radiation (detected by counter), one group exposed to
      an undetectable quantity of radiation, and the non exposed control group.
      RESULTS: The prevalence of thyroid nodules < 1 cm in diameter, defined as
      incidentalomas, in the exposed group with detected doses, was 11.28% in males and
      9.68% in females, while in the exposed group with undetectable dose the
      prevalence was 10.39% in males and 16.67% in females. In the non exposed group
      the prevalence of incidentalomas was 9.34% in males and 13.20% in females. These
      prevalences were not statistically different when analysed by a multiple test
      comparison with the bootstrap method and stratification for sex. Instead, the
      prevalence of thyroid nodules > 1 cm in diameter resulted statistically different
      in exposed and non exposed health staff: 18.68% in non exposed males vs exposed:
      3.76% (determined dose) and 9.09% (undetectable dose) in males, and 20.30% in non
      exposed females versus 3.23% (detected dose) and 9.52% (undetectable dose) in
      exposed females. There was a higher proportion of healthy staff in the exposed
      group than in the non exposed: (80.45% vs 68.68% in males; 80.65% vs 57.87% in
      females). CONCLUSION: In our study, occupational exposure to radiation combined
      with mild iodine deficiency did not increase the risk of developing thyroid
      nodules. The statistically significant higher prevalence of thyroid nodules in
      the non exposed group could be explained by the high percentage (22%) of people
      with a familial history of, and hence a greater predisposition to, thyroid
      disease. The endemic condition of mild iodine deficiency, demonstrated in other
      studies, played a major role in determining the thyroid pathology in our study
      groups.

PMID- 16000194
TI  - Microinjections of nociceptin into the nucleus ambiguus elicit tachycardia in the
      rat.
AB  - Cardiovascular effects of activation of opioid receptor like receptors (ORL1
      receptors) in the nucleus ambiguus were studied in urethane-anesthetized, adult
      male Wistar rats. Microinjections of nociceptin (0.31, 0.62, 1.25 and 2.25
      mmol/L) into the nucleus ambiguus elicited increases in heart rate (17.5 +/- 4,
      33.3 +/- 2.9, 16.5 +/- 1.5 and 13.9 +/- 2.7 beats/min, respectively) which were
      blocked by an ORL1 receptor antagonist. These results indicate that activation of
      ORL1 receptors in the nucleus ambiguus elicits tachycardia.

PMID- 16000195
TI  - The biological impact of estrogens on gender differences in congestive heart
      failure.

PMID- 16000196
TI  - Prostaglandin D2 and prostaglandin E2 accelerate the recovery of cutaneous
      barrier disruption induced by mechanical scratching in mice.
AB  - The role of prostaglandins in mechanical scratching-induced cutaneous barrier
      disruption in mice was investigated. Skin prostaglandins contents were measured
      after cutaneous barrier function was disrupted by scratching using a stainless
      steal wire brush (mechanical scratching), then effects of prostanoids on recovery
      of cutaneous barrier functions were examined. This mechanical scratching
      increased transepidermal water loss and skin prostaglandins (prostaglandin D2,
      prostaglandin E2, 6-keto-prostaglandin F1alpha and prostaglandin F2alpha)
      contents, count-dependently. Topical application of indomethacin immediately
      after cutaneous barrier disruption delayed the recovery period of cutaneous
      barrier disruption. We examined effects of several prostanoids (prostaglandin D2,
      prostaglandin E2, prostaglandin F2alpha, prostaglandin I2 and U46619) on delay of
      the recovery process of mechanical scratching-induced cutaneous barrier
      disruption with treatment of indomethacin. Topically applied prostaglandin D2 and
      prostaglandin E2 accelerated the recovery of cutaneous barrier disruption and
      topical application of prostaglandin J2, limaprost, sulprostone and ONO-4819, but
      not 13,14-dihydro-15-keto-prostaglandin D2, 15-deoxy-Delta(12,14)-prostaglandin
      J2, 17-phenyl-trinor-prostaglandin E2 or butaprost had effects on recovery of the
      cutaneous barrier. These results suggest that prostaglandin D2 and prostaglandin
      E2 accelerate the recovery process of cutaneous barrier disruption caused by
      mechanical scratching, via specific prostanoid DP1, EP3 and EP4 receptors.

PMID- 16000197
TI  - Septal innervation regulates the function of alpha7 nicotinic receptors in CA1
      hippocampal interneurons.
AB  - The hippocampus receives substantial input from the medial septum/diagonal band
      of broca (MS/DB) via the fibria-fornix (FF). Projections from the MS/DB innervate
      hippocampal interneurons that express alpha7 nicotinic receptors and regulate
      excitation in principal cell populations. In the present report we used
      stereotaxic surgery, whole-cell patch clamping, and immunohistochemical
      techniques to evaluate the effects of FF and MS/DB lesions on alpha7 nicotinic
      receptors in stratum radiatum interneurons. Focal somatic application of ACh (1
      mM) evoked methyllycaconitine (MLA)-sensitive currents that were markedly reduced
      following aspirative lesions of the FF. Reductions in current amplitudes were
      prevented or restored to levels not significantly different from controls
      following in vivo treatment with the alpha7-selective agonist GTS-21, and GTS-21
      treatment did not change current amplitudes measured in tissue from unlesioned
      animals. MS/DB injections of the selective cholinergic neurotoxin 192 IgG-saporin
      did not affect alpha7 receptor currents, although MS/DB ChAT and hippocampal AChE
      immunolabeling were significantly reduced. In contrast, kainic acid lesions of
      the MS/DB, potentially more selective for GABAergic projection neurons, produced
      significant reductions in current amplitudes. These findings are the first to
      show functional changes in alpha7 receptors following hippocampal denervation and
      suggest that MS/DB hippocampal innervation regulates functional aspects of
      hippocampal alpha7 receptors. The results confirm hippocampal alpha7 nicotinic
      receptors as viable therapeutic targets in diseases that involve degradation of
      the septohippocampal pathway and may indicate that GABAergic MS/DB hippocampal
      input plays a more substantial role in the regulation of alpha7 nicotinic
      receptor function than MS/DB hippocampal cholinergic input.

PMID- 16000198
TI  - NF-kappaB activation but not PI3K/Akt is required for dexamethasone dependent
      protection against TNF-alpha cytotoxicity in L929 cells.
AB  - Tumor necrosis factor alpha (TNF-alpha) is one of the best-described cell death
      promoters. In murine L929 fibroblasts, dexamethasone inhibits TNF-alpha-induced
      cytotoxicity. Since phosphatidyl inositol 3 kinase (PI3K) and nuclear factor
      kappa B (NF-kappaB) proteins regulate several survival pathways, we evaluated
      their participation in dexamethasone protection against TNF-alpha cell death. We
      interfered with these pathways by overexpressing a negative dominant mutant of
      PI3K or a non-degradable mutant of inhibitor of NF-kappaB alpha (IkappaBalpha)
      (the cytoplasmic inhibitor of NF-kappaB) in L929 cells. The mutant IkappaB, but
      not the mutant PI3K, abrogated dexamethasone-mediated protection. The loss of
      dexamethasone protection was associated with a diminished accumulation in XIAP
      and c-IAP proteins.

PMID- 16000199
TI  - Effects of environmental conditions, human activity, reproduction, antler cycle
      and grouping on fecal glucocorticoids of free-ranging Pampas deer stags
      (Ozotoceros bezoarticus bezoarticus).
AB  - In this study, a commercial enzyme immunoassay (EIA) was validated in detecting
      glucocorticoids in Pampas deer feces, in order to investigate the influence of
      several factors on the adrenocortical function. Fecal samples, behavioral data
      and information concerning male grouping and antlers status were collected at a
      monthly basis during a 1 year period from free-ranging stags living at Emas
      National Park, Brazil (18 degrees S/52 degrees W). The results revealed that
      concentrations of fecal glucocorticoids in winter were significantly higher than
      those corresponding to spring and summer. In addition, dry season data presented
      higher levels than during the wet season. Significant difference was found
      between fecal levels of breeding stags in summer and nonbreeding stags, whereas
      no difference was observed between breeding stags in winter and nonbreeding
      stags. On the other hand, males from areas with frequent human disturbance
      exhibited higher glucocorticoid concentrations and flight distances than
      individuals from areas of lower human activity. Males with antlers in velvet had
      elevated levels compared with animals in hard antler or antler casting. Also, we
      found that glucocorticoid levels were higher in groups with three or more males
      than in groups with only one male. The flight distances showed positive
      correlation with fecal glucocorticoid. These data indicate that fecal
      glucocorticoid provides a useful approach in the evaluation of physiological
      effects of environment, inter-individuals relationship and human-induced
      stressors on free-ranging Pampas deer stags.

PMID- 16000200
TI  - Probabilistic order in antigenic variation of Trypanosoma brucei.
AB  - Antigenic variation in African trypanosomes displays a degree of order that is
      usually described as 'semi-predictable' but which has not been analysed in
      statistical detail. It has been proposed that, during switching, the variable
      antigen type (VAT) being inactivated can influence which VAT is subsequently
      activated. Antigenic variation proceeds by the differential activation of members
      of the large archive of distinct variable surface glycoprotein (VSG) genes. The
      most popular model for ordered expression of VATs invokes differential activation
      probabilities for individual VSG genes, dictated in part by which of the four
      types of genetic locus they occupy. We have shown, in pilot experiments in
      cattle, correlation between the timing of appearance of VSG-specific mRNA and of
      lytic antibodies corresponding to seven VSGs encoded by single-copy genes. We
      have then determined the times of appearance of VAT-specific antibodies, as a
      measure of appearance of the VATs, in a statistically significant number of mouse
      infections (n=22). There is a surprisingly high degree of order in temporal
      appearance of the VATs, indicating that antigenic variation proceeds through
      order in the probability of activation of each VAT. In addition, for the few
      examples of each available, the locus type inhabited by the silent 'donor' VSG
      plays a significant role in determination of order. We have analysed in detail
      previously published data on VATs appearing in first relapse peaks, and find that
      the variant being switched off does not influence which one is being switched on.
      This differs from what has been reported for Plasmodium falciparum var antigenic
      variation. All these features of trypanosome antigenic variation can be explained
      by a one-step model in which, following an initial deactivation event, the switch
      process and the imposition of order early in infection arise from the inherent
      activation probabilities of the specific VSG being switched on.

PMID- 16000201
TI  - Mechanobiology of tendon.
AB  - Tendons are able to respond to mechanical forces by altering their structure,
      composition, and mechanical properties--a process called tissue mechanical
      adaptation. The fact that mechanical adaptation is effected by cells in tendons
      is clearly understood; however, how cells sense mechanical forces and convert
      them into biochemical signals that ultimately lead to tendon adaptive
      physiological or pathological changes is not well understood. Mechanobiology is
      an interdisciplinary study that can enhance our understanding of
      mechanotransduction mechanisms at the tissue, cellular, and molecular levels. The
      purpose of this article is to provide an overview of tendon mechanobiology. The
      discussion begins with the mechanical forces acting on tendons in vivo, tendon
      structure and composition, and its mechanical properties. Then the tendon's
      response to exercise, disuse, and overuse are presented, followed by a discussion
      of tendon healing and the role of mechanical loading and fibroblast contraction
      in tissue healing. Next, mechanobiological responses of tendon fibroblasts to
      repetitive mechanical loading conditions are presented, and major cellular
      mechanotransduction mechanisms are briefly reviewed. Finally, future research
      directions in tendon mechanobiology research are discussed.

PMID- 16000202
TI  - Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells:
      Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein
      response.
AB  - The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension
      by inducing a "megalocytosis" phenotype in target pulmonary arterial endothelial,
      smooth muscle and Type II alveolar epithelial cells. In cultured endothelial
      cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP)
      results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and
      increased vacuoles. However, these cells fail to enter mitosis. Largely based
      upon data from endothelial cells, we proposed earlier that a disruption of the
      trafficking and mitosis-sensor functions of the Golgi (the "Golgi blockade"
      hypothesis) may represent the subcellular mechanism leading to MCTP-induced
      megalocytosis. In the present study, we investigated the applicability of the
      Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis
      in cultures of lung A549 and breast MCF-7 cells. This was associated with a
      change in the distribution of the cis-Golgi scaffolding protein GM130 from a
      discrete juxtanuclear localization to a circumnuclear distribution consistent
      with an anterograde block of GM130 trafficking to/through the Golgi. There was
      also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together
      with a circumnuclear accumulation of clathrin heavy chain (CHC) and alpha
      tubulin. Flotation analyses revealed losses/alterations in the association of
      caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis
      was accompanied by an enhanced unfolded protein response (UPR) as evidenced by
      nuclear translocation of Ire1alpha and glucose regulated protein 58 (GRP58/ER
      60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide
      isomerase (PDI). These data further support the hypothesis that an MCTP-induced
      Golgi blockade and enhanced UPR may represent the subcellular mechanism leading
      to enlargement of ER and Golgi and subsequent megalocytosis.

PMID- 16000203
TI  - A comparison between integrated risk assessment and classical
      health/environmental assessment: emerging beneficial properties.
AB  - Both humans and wildlife are exposed to various types of halogenated organic
      compounds such as polychlorinated biphenyls (PCBs) and
      dichlorodiphenyltrichloroethane (DDT), typically old chemicals, and tris(4
      chlorophenyl) methane (TCPM) and brominated flame retardants, some new chemicals,
      simultaneously. Classical risk assessment has evaluated health and ecological
      risks independently by experts from different disciplines. Taking into
      considerations the recent concerns about endocrine disrupting chemicals and the
      progress of research in related areas, we integrated and assessed data on
      exposure and potential effects in humans and wildlife. Comparisons were made for
      organ concentrations, body burdens of several organochlorine compounds (OCs),
      metabolic capacities between humans and various wildlife. When we integrate the
      knowledge on effects and exposure in humans and in wildlife, new insights were
      suggested about similarities and/or differences in potential effects among
      various human populations living on different foods and having different body
      burdens. Combining existing information with emerging knowledge of mechanisms of
      actions on endocrine disrupting chemicals after exposure to above chemicals
      during early developmental stages will further elucidate potential risks from
      exposure to those chemicals.

PMID- 16000204
TI  - In vitro assessment of sensitizing activity of low molecular weight compounds.
AB  - Predictive tests to identify the sensitizing properties of chemicals are carried
      out using animals. There is as yet, no accepted in vitro method for the
      identification of skin sensitizing chemicals. Such in vitro tests should
      encompass (parts of) the sensitization phase of contact hypersensitivity. Two
      cell types are predominantly involved in this process, keratinocytes (KC) and
      Langerhans cells, the latter being a specialized type of skin dendritic cells
      (DC). Low molecular weight chemicals act as haptens; KC respond to allergen
      contact by, among others, producing proinflammatory cytokines, while DC take up
      the haptenized protein, migrate, and present antigen to T-cells. During
      migration, DC mature, resulting in a loss of antigen uptake capacity, thereby
      increasing expression of certain surface molecules. Thus, both cytokine
      production by KC and surface marker expression by DC may be used as in vitro
      models for the identification of sensitizers. Several reports have shown that
      intracellular IL-1 alpha is a promising candidate to identify sensitizers using
      KC. We have recently shown that the potency of sensitizers may be determined by
      dose-response analysis of intracellular IL-1 alpha and IL-18 using a murine KC
      cell line. The ranking of potency using this in vitro method was similar to the
      ranking previously established using the local lymph node assay. Using DC,
      effects on the expression of various cell surface markers, cytokines, and
      molecules involved in antigen uptake have been shown to identify sensitizers. One
      study showed that also the potency of sensitizers may be determined using DC.
      Additional studies are required to establish whether KC or DC, or combinations
      thereof, are most suitable for in vitro identification and potency assessment of
      sensitizers.

PMID- 16000205
TI  - Thresholds of allergenic proteins in foods.
AB  - Threshold doses or Estimated Eliciting Doses (EEDs) represent an important new
      field of research in food allergy. Clinicians and regulators have embraced some
      toxicological concepts such as LOAEL and NOAEL and applied them to an area of
      significant clinical uncertainty and interest. The impact of intrinsic human
      factors (e.g., asthma and exercise) and extrinsic event factors (e.g., season,
      location and especially dose of allergen) on a future allergic reaction in the
      community needs to be considered carefully when interpreting results of clinical
      and research low-dose food challenges. The ongoing cooperation of food allergy
      research groups in medicine, food science and government will surely deliver
      results of the highest importance to the wider communities of allergology, food
      science and technology and the increasing number of allergic consumers.

PMID- 16000206
TI  - Effect of iron on the sensitivity of hydrogen, acetate, and butyrate metabolism
      to inhibition by long-chain fatty acids in vegetable-oil-enriched freshwater
      sediments.
AB  - Freshwater sediment microbial communities enriched by growth on vegetable oil in
      the presence of a substoichiometric amount of ferric hydroxide (sufficient to
      accept about 12% of the vegetable-oil-derived electrons) degrade vegetable oil to
      methane faster than similar microbial communities that develop when sediments are
      enriched by growth on vegetable oil in the absence of ferric hydroxide. This
      study examined the effects of enrichment in the presence of Fe(III) on the fatty
      acid sensitivity of several important members of anaerobic triglyceride-degrading
      microbial communities in freshwater sediments. The fatty-acid sensitivity of
      three groups of microorganisms-hydrogenotrophic methanogens, acetate consumers,
      and hydrogen-producing acetogens-were investigated by comparing the rates of
      hydrogen, acetate, or butyrate consumption in the presence and absence of oleic
      acid. Methanogenesis from hydrogen was not affected by sediment enrichment
      conditions or by the presence of oleic acid, suggesting that hydrogenotrophic
      methanogens were insensitive to fatty acid inhibition in these sediments. Oleic
      acid inhibited the anaerobic degradation rates of acetate and butyrate by 38% and
      63%, respectively, but enrichment in the presence of Fe(III) eliminated the fatty
      acid sensitivity of acetate degradation and reduced the sensitivity of butyrate
      degradation by about half. These results suggest that iron-reducing bacteria may
      provide an alternative pathway through which vegetable oil can be converted to
      methane in anaerobic freshwater sediments.

PMID- 16000207
TI  - Synergistic inactivation of Cryptosporidium parvum using ozone followed by
      monochloramine in two natural waters.
AB  - The effect of sequential exposure to ozone followed by monochloramine on
      inactivation of Cryptosporidium parvum oocysts suspended in untreated natural
      surface water from two different sources was studied in bench-scale batch
      reactors. Animal infectivity using neonatal CD-1 mice was used to measure oocyst
      inactivation. A statistically significant synergistic effect on oocyst
      inactivation was measured in both natural water samples studied. The magnitude of
      the effect measured in the natural water with lower turbidity, colour, and
      organic carbon concentration was comparable to that previously reported for
      oocysts suspended in buffered de-ionized water but was reduced considerably in
      the natural water with higher turbidity, colour and organic carbon concentration.
      Synergy increased with initial pH and with the degree of ozone pre-treatment but
      was independent of temperature. For water treatment plants with adequate
      disinfectant contact times, ozone followed by monochloramine may be a practical
      means of achieving additional C. parvum inactivation, however, the influence of
      water quality characteristics should be considered.

PMID- 16000208
TI  - Use of fungi to improve bioconversion of activated sludge.
AB  - The present study was designed to evaluate the potential of microbial adaptation
      and its affinity to biodegradation as well as bioconversion of soluble/insoluble
      (organic) substances of domestic wastewater treatment plant (DWTP) sludge
      (activated domestic sludge) under natural/non-sterilized conditions. The two
      filamentous fungi, Penicillium corylophilum (WWZP1003) and Aspergillus niger
      (SCahmA103) were used to achieve the objectives. It was observed that P.
      corylophilum (WWZP1003) was the better strain compared to A. niger (SCahmA103)
      for the bioconversion of domestic activated sludge through adaptation. The visual
      observation in plate culture showed that about 95-98% of cultured microbes (P.
      corylophilum and A. niger) dominated in treated sludge after 2 days of treatment.
      In this study, it was also found that the P. corylophilum was capable of removing
      94.40% of COD and 98.95% of turbidity of filtrate with minimum dose of inoculum
      of 10% v/v in DWTP sludge (1% w/w). The pH level was lower (acidic condition) in
      the fungal treatment and maximum reduction of COD and turbidity was observed (at
      lower pH). The results for specific resistance to filtration (SRF) showed that
      the fungi played a great role in enhancing the dewaterability and filterability.
      In particular, the strain Penicillium had a more significant capability (than A.
      niger) of reducing 93.20% of SRF compared to the uninoculated sample. Effective
      results were observed by using fungal inoculum after 2 days of treatment. The
      developed LSB process is a new biotechnological approach for sludge management
      strategy.

PMID- 16000209
TI  - Combined nitrification/denitrification in a membrane reactor.
AB  - An ever stricter legislation regulating wastewater leads to an increasing demand
      for biological treatment plants which are able to selectively eliminate nitrogen
      from wastewaters with a high influent concentration, even when operating in
      partial influent mode. A membrane-tube-module (MSM) reactor (Membran-Schlauch
      Modul-Reaktor) was constructed and realized in the IUV at the University of
      Bremen. The present approach makes use of all the various layers of the whole
      biofilm, enabling nitrification and denitrification processes to run
      simultaneously in one and the same biofilm under optimized conditions. The
      biological degradation capacity of the system was first successfully tested with
      synthetic wastewater, and subsequently in a real application with effluents from
      a recycling of animal carcasses plant and from a coke-oven plant. A mathematical
      model was devised which describes this biofilm system. The resulting equations
      were solved by means of the simulation software AQUASIM.

PMID- 16000210
TI  - A review of floc strength and breakage.
AB  - The main focus of the paper is to review current understanding of floc structure
      and strength. This has been done by reviewing current theoretical understanding
      of floc growth and breakage and an analysis of different techniques used for
      measuring floc strength. An overview has also been made of the general trends
      seen in floc strength analysis. The rate of floc formation is a balance between
      breakage and aggregation with flocs eventually reaching a steady-state size for a
      given shear rate. The steady-state floc size for a particular shear rate can,
      therefore, be a good indicator of floc strength. This has resulted in the
      development of a range of techniques to measure floc size at different applied
      shear levels using a combination of one or more of the following tools: light
      scattering and transmission; microscopy; photography; video and image analysis
      software. Floc strength may be simply quantified using the initial floc size for
      a given shear rate and the floc strength factor. More complex techniques have
      used theoretical modelling to determine whether flocs break by large-scale
      fragmentation or smaller-scale surface erosion effects, although this
      interpretation is open to debate. Impeller-based mixing, ultrasound and vibrating
      columns have all been used to provide a uniform, accurate and controllable
      dissipation of energy onto a floc suspension to determine floc strength. Other
      more recent techniques have used sensitive micromanipulators to measure the force
      required to break or compress individual flocs, although these techniques have
      been limited to the measurement of only a few hundred flocs. General trends
      emerge showing that smaller flocs tend to have greater strength than larger
      flocs, whilst the use of polymer seems to give increased strength to only some
      types of floc. Finally, a comparison of the strength of different types of floc
      (activated sludge flocs, organic matter flocs, sweep flocs and charge neutralised
      flocs) has been made highlighting differences in relative floc strength.

PMID- 16000211
TI  - Influence of operating conditions on the ammonia electro-oxidation rate in
      wastewaters from power plants (ELONITA technique).
AB  - Power plants, like many other industries, are confronted with the need to reduce
      the nitrogen content of their wastewaters. Indirect electro-oxidation, through
      hypochlorite formation, is a possible answer to an ammonia-nitrogen problem,
      through converting it into gaseous nitrogen. Several parameters affect the
      ammonia oxidation rate: current density, chloride concentration and the presence
      of oxygen-containing anions, mainly SO(4)(2-), CO(3)(2-) and PO(4)(3-). pH values
      between 5.5 and 10 have been found to have no effect on the ammonia oxidation
      rate. However, at higher pH values (above 11), the oxidation slows down and
      chlorate ions appear. A model can be fitted from the experiments to predict the
      ammonia oxidation rate based on four main parameters: pH, current density,
      sulfate concentration and chloride concentration. The average difference between
      the predicted oxidation rates and the experimental measures is only 6.5%. This
      model confirms that the optimal operating conditions are a high chloride
      concentration (7 gl(-1)), no sulfate and a high current density (1200 Am(-2)).

PMID- 16000212
TI  - Leaching and reduction of chromium in soil as affected by soil organic content
      and plants.
AB  - The oxidation state of chromium in contaminated soils is an important indicator
      of toxicity and potential mobility. Chromium in the hexavalent state is highly
      toxic and soluble, whereas the trivalent state is much less toxic and relatively
      insoluble. A laboratory study investigated the impact of growing plants and
      supplemental organic matter on chromium transport in soil. Plants alone had no
      appreciable effect on the chromium oxidation state in soil. Soil columns with
      higher organic content were associated with lower ratios of chromate:total
      chromium than the columns with lower organic matter. Analyses of column leachate,
      plant biomass, and soil indicate that more chromium leaching occurred in the
      vegetated, low organic columns. Retention of Cr in the soils was correlated to
      the Cr(III) content. Plant uptake of chromium accounted for less than 1% of the
      chromium removed from the soil. Overall, the addition of organic matter had the
      strongest influence on chromium mobility.

PMID- 16000213
TI  - Cell biological evaluation of liver cell carcinoma, dysplasia and adenoma by
      tissue micro-array analysis.
AB  - The clinical and morphological definition of hepatocellular carcinoma (HCC),
      dysplasia and adenoma suffers from a lack of biological understanding. This is
      especially important in the histomorphological diagnosis of nodular liver lesions
      in needle biopsies. Therefore, we constructed a liver tissue micro-array (TMA)
      and evaluated 48 HCCs, 46 dysplasias, 8 adenomas, 20 cirrhotic specimens and 28
      normal liver samples derived from 68 patients. Protein (over)expression by tumor
      suppressor genes p16, p53 and Rb1 was assessed by immunohistochemistry, the
      proliferative capacity was examined by immunostaining of Ki67. Further, DNA
      ploidy status (hyperdiploidy) was measured by fluorescent in situ hybridization
      (FISH) with a chromosome 1-specific repetitive DNA probe. An abnormal chromosome
      1 number, i.e. the percentage of hyperdiploid cells, was 11.0, 13.7, 16.1, 23.7
      and 31.3 for normal liver samples, adenomas, cirrhosis, dysplasias and HCCs,
      respectively. A significant difference was found for HCC versus cirrhosis (P =
      0.024) or adenoma (P = 0.033), a trend (borderline significance) was seen for
      dysplasia versus cirrhosis (P = 0.094). Immunohistochemical protein localisation
      of p53 and Rb1, as well as Ki67 indicating proliferation, was clearly higher in
      HCC than in cirrhosis or dysplasia (all P < 0.001). Proliferation was also higher
      in HCC than in adenoma (P = 0.025), whereas a trend (borderline significance) was
      observed for Rb1 overexpression (P = 0.063). These data suggest that in the liver
      cell dysplasia-carcinoma pathway, changes in ploidy are followed by increased
      proliferation and cell biological perturbations involving p53 and Rb1. Adenomas
      can be distinguished from carcinomas, but not from dysplasias, based on ploidy
      and proliferation characteristics.

PMID- 16000214
TI  - Transcriptional expression of the genes implicated in angiogenesis and tumor
      invasion in cervical carcinomas.
AB  - OBJECTIVE: Co-expression patterns of the genes implicated in angiogenesis and
      tumor invasion in cervical carcinoma cells were investigated together with
      invasive activity of tumor cells. Transcript levels of those genes were also
      compared between tumor cells and normal cervical tissues. METHODS: Real-time
      quantitative RT-PCR analysis was conducted on selected 11 genes (total VEGF-A,
      VEGF(121), VEGF(165), VEGF(189), VEGF-B, C and D, bFGF, dThdPase, MMP-2 and uPA)
      using 11 cervical carcinoma cell lines and 14 normal cervical tissues. Protein
      expression of VEGF-C and MMP-2 and invasive activity of tumor cells were
      evaluated for each cell line by sandwich ELISA and haptoinvasion assay,
      respectively. RESULTS: Gene co-expression analysis revealed the significant
      correlation between angiogenic factors and proteinases in malignant but not in
      normal cervical samples. Gene or protein expression levels of VEGF-C and MMP-2
      were well correlated with the number of invaded tumor cells. VEGF-A splicing
      variants were increased in malignant compared to normal cervical samples but not
      associated with the invasive activity of the cells. CONCLUSION: VEGF-C and MMP-2
      were closely related to invasive phenotype of tumor cells, whereas VEGF-A
      isoforms were considered to be involved in cervical carcinogenesis.

PMID- 16000215
TI  - Conservation of in vitro drug resistance patterns in epithelial ovarian
      carcinoma.
AB  - PURPOSE: To compare the in vitro drug resistance profiles of advanced stage
      primary and recurrent epithelial ovarian cancer specimens using the tritiated
      thymidine uptake assay. METHODS: Extreme drug resistance (EDR) to cisplatin,
      paclitaxel, 4-hydroxycyclophosphamide, and topotecan was determined for an
      unselected population of primary and metastatic malignant ovarian tissues,
      synchronous tumors (primary and metastatic tissues obtained from the same patient
      at diagnosis), and metachronous lesions (specimens from the same patient before
      and after chemotherapy). RESULTS: For the large unselected population of
      malignant tissues (total, N = 6990; primary ovarian, N = 2031; metastatic
      ovarian, N = 4959), no statistically significant differences were discovered
      between primary tissues and metastatic lesions when a comparison was made between
      the percentage of tumors from each group that exhibited extreme drug resistance
      to the agents assayed. From the library of 6990 specimens, 119 synchronous
      pairings were identified. These synchronous lesions did not differ significantly
      in the %EDR between primary and metastatic sites in the same patient;
      approximately 10% shifted between low drug resistance and EDR. A total of 334
      metachronous pairings were identified and the percentage of tissues that
      exhibited EDR also failed to show a significant difference when primary tumors
      were compared with matched recurrences in the same patient. CONCLUSIONS: For the
      agents studied, acquired resistance was not a function of disease site. In vitro
      drug resistance observed at recurrence was not influenced significantly by
      intervening therapy. It is possible that assay results at diagnosis could be used
      to guide subsequent therapy at relapse, especially when recurrent tissue is not
      available for analysis.

PMID- 16000216
TI  - Treatment patterns by decade of life in elderly women (> or =70 years of age)
      with ovarian cancer.
AB  - OBJECTIVE: Elderly patients are less likely to receive surgery and platinum-based
      combination chemotherapy than younger patients. We evaluated multi-institutional
      management of ovarian cancer in the elderly. METHODS: Charts of women with
      ovarian, primary peritoneal or fallopian tube cancer from 1/1996-6/2004, age > or
      =70 years were reviewed. Age, stage, medical co-morbidities, surgery,
      chemotherapy, treatment modification, toxicity and survival were analyzed. Chi
      square, logistic regression and survival analysis were used. RESULTS: Of 131
      patients, 90 were ages 70-79 (group 1 = G1) and 41 were >80 years of age (group 2
      = G2). Surgery was performed in 80 patients in G1; 25 patients in G2 (P = 0.001).
      Among patients who underwent surgery, optimal debulking and post-operative
      complications did not differ between groups. Ninety-five percent of patients
      received platinum-based therapy and 83% received combination platinum/paclitaxel
      in G1, compared to 90% and 41%, respectively, in G2 (P < 0.001). Of those
      receiving platinum therapy, 36% in G1 and 41% in G2 required dose reductions or
      termination of therapy. Forty percent of G1 and 50% of G2 required a delay of
      therapy; the majority occurring in patients receiving combination therapy.
      Hematological toxicity increased with use of combination therapy, but not with
      advancing age or Charlson score. Successful debulking surgery significantly
      impacted survival, and when controlling for this factor, age was not a
      significant variable. CONCLUSION: The extreme elderly had a decreased likelihood
      of receiving surgery and combination chemotherapy despite equivalent co
      morbidities. In this analysis, optimal surgical cytoreduction had the greatest
      impact on survival.

PMID- 16000217
TI  - A comparison of the locomotor stimulant effects of D1-like receptor agonists in
      mice.
AB  - Efficacy in stimulating adenylyl cyclase (AC) has traditionally been used to
      distinguish dopamine D1-like receptor agonists from dopamine D2-like receptor
      agonists. However, there is a limited association between the effects of D1-like
      agonists in behavioral assays and their effectiveness at stimulating AC. Other
      second messenger actions might contribute to the behavioral effects of D1-like
      agonists, as there is evidence for a link to the hydrolysis of phosphoinositide
      (PI). The present study compared the locomotor stimulant effects of five D1-like
      receptor agonists having different efficacies in assays of AC and PI activity.
      All D1-like agonists produced long-lasting biphasic effects on locomotor
      activity. SKF 38393, the prototypical partial agonist (based on AC activity),
      produced limited changes in locomotor activity, whereas the partial agonists SKF
      75670 and SKF 77434 produced locomotor stimulant effects that were similar to or
      greater than those of the full efficacy agonists SKF 82958 and SKF 81297.
      However, there did not appear to be a relationship between maximal behavioral
      effects and AC stimulation or PI hydrolysis. The results suggest a complex
      relationship between the behavioral effects of D1-like agonists and their
      intrinsic efficacies as measured by AC and /or PI stimulation. Although a limited
      number of compounds were examined, neither second messenger system alone appears
      to account fully for these behavioral effects. The current classification of D1
      like agonists according to their intrinsic efficacies as defined by AC
      stimulation needs further scrutiny.

PMID- 16000218
TI  - Factorial analysis of variables influencing stress in all-ceramic crowns.
AB  - OBJECTIVE: The objective of this investigation was to evaluate the relative
      contribution of variables in the crown-cement-tooth system that can influence
      magnitude of maximum principal stress in all-ceramic crowns. METHODS.: Factorial
      analysis was performed to calculate the coefficients of main and interactive
      effects of seven variables on maximum stress distribution in a series of finite
      element models of an axisymmetric stylized ceramic crown-cement-tooth system.
      Variables investigated at two levels were selected for their clinical relevance
      and included those relating to crown material and geometry (thickness and cuspal
      incline), cement modulus and thickness, supporting tooth core, and position at
      which the occlusal load was applied. RESULTS: The average principal stress for
      all combinations of all variables was 135.1 MPa but stress magnitude ranged from
      73.7 to 214.0 MPa. Crown material and thickness are of primary importance in
      stress magnitude but other variables (cement modulus, load position, and
      supporting tooth core) also contribute to the stress magnitude. Interactions
      between these variables can have an important influence, particularly since the
      stress in the crown is not necessarily sensitive to the same factors for all
      crown material systems. SIGNIFICANCE: Comprehensive evaluation of stress in a
      crown of a crown-cement-tooth system must integrate the influence of single
      variables and their interactions.

PMID- 16000220
TI  - Three-dimensional growth of differentiating MC3T3-E1 pre-osteoblasts on porous
      titanium scaffolds.
AB  - The present work assesses the potential of three-dimensional porous titanium
      scaffolds produced by a novel powder metallurgy process for applications in bone
      engineering through in vitro experimentation. Mouse MC3T3-E1 pre-osteoblasts were
      used to investigate the proliferation (DNA content), differentiation (alkaline
      phosphatase activity and osteocalcin release) and mineralisation (calcium
      content) processes of cells on titanium scaffolds with average pore sizes ranging
      from 336 to 557 microm, using mirror-polished titanium as reference material.
      Scanning electron microscopy was employed to qualitatively corroborate the
      results. Cells proliferate on all materials before reaching a plateau at day 9,
      with proliferation rates being significantly higher on foams (ranging from 123 to
      163 percent per day) than on the reference material (80% per day). Alkaline
      phosphatase activity is also significantly elevated on porous scaffolds following
      the proliferation stage. However, cells on polished titanium exhibit greater
      osteocalcin release toward the end of the differentiation process, resulting in
      earlier mineralisation of the extracellular matrix. Nevertheless, the calcium
      content is similar on all materials at the end of the experimental period.
      Average pore size of the porous structures does not have a major effect on cells
      as determined by the various analyses, affecting only the proliferation stage.
      Thus, the microstructured titanium scaffolds direct the behaviour of pre
      osteoblasts toward a mature state capable of mineralising the extracellular
      matrix.

PMID- 16000219
TI  - Fabrication of collagen-coated biodegradable polymer nanofiber mesh and its
      potential for endothelial cells growth.
AB  - Endothelialization of biomaterials is a promising way to prevent intimal
      hyperplasia of small-diameter vascular grafts. The aim of this study was to
      design a nanofiber mesh (NFM) that facilitates viability, attachment and
      phenotypic maintenance of human coronary artery endothelial cells (HCAECs).
      Collagen-coated poly(L-lactic acid)-co-poly(epsilon-caprolactone) P(LLA-CL 70:30)
      NFM with a porosity of 64-67% and a fiber diameter of 470+/-130 nm was fabricated
      using electrospinning followed by plasma treatment and collagen coating. The
      structure of the NFM was observed by SEM and TEM, and mechanical property was
      studied by tensile test. The presence of collagen on the P(LLA-CL) NFM surface
      was verified by X-ray photoelectron spectroscopy (XPS) and quantified by
      colorimetric method. Spatial distribution of the collagen in the NFM was
      visualized by labelling with fluorescent probe. The collagen-coated P(LLA-CL) NFM
      enhanced the spreading, viability and attachment of HCAECs, and moreover,
      preserve HCAEC's phenotype. The P(LLA-CL) NFM is a potential material for tissue
      engineered vascular graft.

PMID- 16000221
TI  - Structure-release rate correlation in collagen gels containing fluorescent drug
      analog.
AB  - The paper examines the release properties of collagen gels that contain
      covalently bound fluorescent drug analogs. Collagen gels were prepared by
      fibrilogenesis. The gels were stabilized by cross linking with EDAC/NHS. SEM
      studies showed that increasing the cross-linking time with EDAC/NHS resulted in
      decreasing pore size and increasing gel density. Fluorescence spectroscopy
      measurements showed a clear correlation between decreasing pore size and
      increasing gel density, and lower release rate from the gels. Additives like
      chondrotitin-6-sulfate (CS) and amino acids altered the release properties of the
      cross-linked collagen gels. CS increased the stability of collagen gels to
      enzymatic degradation and non-enzymatic degradation. This was attributed to
      increasing gel rigidity due to carbohydrate-protein interactions. The amino acid
      lysine increased the stability of collagen gels which was attributed to
      increasing cross-linking level between the collagen fibrils and the primary amine
      group on the lysine side chain. The amino acid histidine decreased the stability
      of the gels, particularly to non-enzymatic degradation. These results correlated
      with increasing pore size following treatment with histidine. Our study shows,
      for the first time, a clear correlation between structure and release properties
      of collagen gels. It describes in detail the effect of additives on the
      structural and release properties of collagen gels. The study focused on gels
      that were prepared through fibrillogenesis and were therefore similar in
      structure to native collagen.

PMID- 16000222
TI  - Preparation of hybrid scaffold from fibrin and biodegradable polymer fiber.
AB  - A biodegradable hybrid scaffold was prepared from fibrin and poly(glycolic acid)
      (PGA) fiber. Mixed fibrinogen and thrombin solution homogeneously dispersed in
      the presence of various amounts (0, 1.5, 3.0, and 6.0mg) of PGA fiber was freeze
      dried to obtain fibrin sponges with or without PGA fiber incorporation. By
      scanning electron microscopy observation, the fibrin sponges had an
      interconnected pore structure, irrespective of the amount of PGA fiber
      incorporated. PGA fiber incorporation enabled the fibrin sponges to significantly
      enhance their compression strength. In vitro cell culture studies revealed that
      the number of L929 fibroblasts initially attached was significantly larger for
      any fibrin sponge with PGA fiber incorporation than for the fibrin sponge without
      PGA fiber. The shrinkage of sponges after cell seeding was suppressed by fiber
      incorporation. It is possible that the shrinkage suppression of sponges maintains
      their intraspace, resulting in the superior cell attachment of a sponge with PGA
      fiber incorporation. After subcutaneous implantation into the backs of mice, the
      residual volume of a fibrin sponge with PGA fiber incorporation was significant
      compared with that of a fibrin sponge without PGA fiber. Larger number of cells
      infiltrated deep inside the fibrin sponges with PGA fiber incorporation implanted
      subcutaneously. It is concluded that the fibrin sponge reinforced by fiber
      incorporation is a promising three-dimensional scaffold of cells for tissue
      engineering.

PMID- 16000223
TI  - Safety of gold in stapes surgery.
AB  - Gold prostheses in middle ear surgery were found to have a higher extrusion rate
      than prostheses made from titanium. Incidences of deafness after insertion of a
      gold piston into the vestibule during stapes surgery have been observed. The aim
      of this study was to find out to what degree gold cations can diffuse from the
      prosthesis piston into the perilymph. For this, gold prostheses were incubated in
      artificial perilymph for four months, after which the gold content of the
      perilymph was analysed. As gold exhibits a special behaviour in complex fluids
      like the perilymph, a new analysing method was developed. The results show that
      gold does leak out of the pistons, that it can be reliably measured and that the
      amount of gold reaching the perilymph depends on the contact area. As the amount
      of gold measured in the perilymph stays far below the toxic level, it is very
      unlikely that the gold cations diffusing from a stapes prosthesis into the
      perilymph have a toxic effect on the inner ear hair cells. Inflammatory or
      allergic reactions to gold induced by direct tissue contact, however, cannot be
      excluded.

PMID- 16000224
TI  - Potassium-competitive acid blockade: a new therapeutic strategy in acid-related
      diseases.
AB  - Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer
      disease (PUD), and other acid-related diseases either prevent stimulation of the
      parietal cell (H2 receptor antagonists, H2RAs) or inhibit gastric H+,K+-ATPase
      (e.g., proton pump inhibitors, PPIs). Of the 2 approaches, the inhibition of the
      final step in acid production by PPIs provides more effective relief of symptoms
      and healing. Despite the documented efficacy of the PPIs, therapeutic doses have
      a gradual onset of effect and do not provide complete symptom relief in all
      patients. There is scope for further improvements in acid suppressive therapy to
      maximize healing and offer more complete symptom relief. It is unlikely that
      cholecystokinin2 (CCK2, gastrin) receptor antagonists, a class in clinical
      trials, will be superior to H2RAs or PPIs. However, a new class of acid
      suppressant, the potassium-competitive acid blockers (P-CABs), is undergoing
      clinical trials in GERD and other acid-related diseases. These drugs block
      gastric H+,K+-ATPase by reversible and K+-competitive ionic binding. After oral
      doses, P-CABs rapidly achieve high plasma concentrations and have linear, dose
      dependent pharmacokinetics. The pharmacodynamic properties reflect the
      pharmacokinetics of this group (i.e., the effect on acid secretion is correlated
      with plasma concentrations). These agents dose dependently inhibit gastric acid
      secretion with a fast onset of action and have similar effects after single and
      repeated doses (i.e., full effect from the first dose). Animal studies comparing
      P-CABs with PPIs suggest some important pharmacodynamic differences (e.g., faster
      and better control of 24-hr intragastric acidity). Studies in humans comparing
      PPIs with P-CABs will help to define the place of this new class in the
      management of acid-related diseases.

PMID- 16000225
TI  - Modified cell ELISA to determine the solubilization of cell surface proteins:
      Applications in GPI-anchored protein purification.
AB  - A major step in purifying membrane bound proteins involves the solubilization of
      the protein of interest from the cell membranes. Glycosylphosphatidyl inositol
      (GPI)-anchored proteins pose a singular problem in this solubilization step since
      they are found in detergent-resistant membrane complexes and accordingly are
      insoluble in cold Triton X-100. In this study we have developed a modified cell
      ELISA that determines the solubility of these cell surface proteins under various
      solubilization conditions. Using this non-radioactive method we show that the
      combination of saponin/Triton X-100 at 4 degrees C solubilized GPI-anchored
      proteins more efficiently than Triton X-100 at 4 degrees C. The combination of
      saponin/Triton X-100 at 4 degrees C avoids the potential of activating proteases
      that occurs when using Triton X-100 at 37 degrees C. Furthermore, our method also
      shows the saponin/Triton X-100 solubilized GPI-anchored proteins equivalent to
      the more expensive octyl beta-glucoside. This is a particularly important
      consideration in large-scale protein purification. This method obviates the need
      to use radioactivity, gel electrophoresis and immunoblotting procedures. The
      solubilization conditions determined by this modified ELISA are readily
      translated to the practical application of large-scale protein purification as
      demonstrated in the purification of two different recombinant GPI-anchored
      proteins, GPI-hB7-1 (CD80) and GPI-mICAM-1 (CD54).

PMID- 16000227
TI  - Guidewire and catheter manipulation without coil placement to close minimal
      patent ductus arteriosus.
AB  - BACKGROUND: Transcatheter coil closure (TCC) is safe and effective for most
      patients with PDA, but coil associated complications may occasionally be
      encountered. For occlusion of minimal PDA (<1 mm), we employed a closure protocol
      with guidewire and catheter manipulation. METHODS: Between April 2000 and
      September 2004, 38 patients with a minimal PDA were classified into two groups
      according to the occlusion method at our institution. Group A consisted of 11
      patients (age range 0.7 to 3.5 years; mean age 1.6 years) who underwent guidewire
      and catheter manipulation. Group B consisted of 27 patients (age range 0.5 to 2.7
      years; mean age 1.3 years) who underwent TCC of PDA. RESULTS: In group A (a PDA
      0.4-0.9 mm), 9 (82%) patients had successful closure, and two (18%) patients
      failed the manipulation. No patient had complications during the procedure or
      follow-up. In group B (a PDA 0.5-0.9 mm), 26 (96%) patients had successful
      closure and 1 (4%) patient failed the attempt at TCC. No adverse events of coil
      closure was found during follow-up. Compared to the patients in group B, those in
      group A differed significantly in terms of procedure time. There were no
      significant differences in age, sex, body weight, PDA size, fluoroscopy time,
      success rate, and complication rate. CONCLUSIONS: Our results indicate that the
      manipulation is safe and effective for patients with minimal PDA. The
      manipulation technique can be tried before TCC in patients with minimal PDA.

PMID- 16000226
TI  - Offspring from families at high risk for alcohol dependence: increased body mass
      index in association with prenatal exposure to cigarettes but not alcohol.
AB  - The prevalence of overweight and obese children is increasing, a tendency that
      can be expected to increase the risk of adverse outcomes in adulthood. The aim of
      this study was to determine if prenatal exposure to alcohol, cigarettes, and
      street drugs would be associated with differences in body mass index (BMI) in
      childhood and adolescence in offspring from families at high and low genetic risk
      for developing alcohol dependence. Annual follow-up of offspring (N = 288)
      provided 1200 height and weight assessments for analysis. Maternal substance use
      data were available for 235 offspring from families stratified for
      familial/genetic risk for alcohol dependence (high or low risk), providing the
      opportunity to assess prenatal exposure and familial/genetic risk in relation to
      BMI in the offspring. When data were grouped by the presence or absence of any
      prenatal cigarette exposure, a significant difference in offspring BMI was seen
      for 8- to 11-year-olds. Significant group differences were also seen at ages 12
      15 and 16-18 years. A dose-response relationship between cigarette use by the
      mother and offspring BMI was also seen. With the strong tendency for individuals
      who are overweight in childhood and adolescence to become overweight adults,
      prenatal exposure to nicotine may be a harbinger of increased risk for numerous
      adult-onset, weight-related health problems.

PMID- 16000228
TI  - Aortic root dilatation with redundancy of mitral and aortic leaflets associated
      with the LEOPARD syndrome.

PMID- 16000229
TI  - Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N
      neurons.
AB  - Changes in gonadal steroid hormone levels during the menstrual cycle affect
      seizure frequency in women with catamenial epilepsy. Since GABA(A) receptors
      (GABARs) contribute to the prevention and termination of seizures by reducing
      neuronal excitability, we hypothesized that fluctuating gonadal steroid levels
      might affect GABAR subunit expression, which could alter inhibitory tone leading
      to increased seizure activity. To address this question in a simplified
      environment in vitro, we examined the effects of gonadal steroids on NT2-N
      neuronal cells. We have previously shown that NT2-N cells express functional
      GABARs, and that the expression pattern of GABAR subunits is regulated by chronic
      benzodiazepine exposure and hypoxia. NT2-N neurons were exposed to progesterone
      (0.1 microM), beta-estradiol (3 nM), or vehicle (DMSO) for 2 days or 7 days prior
      to RNA harvesting. GABAR subunit mRNA levels were assessed by semiquantitative RT
      PCR normalized to actin levels. Progesterone exposure for 7 days increased alpha2
      and gamma3 and decreased alpha5 subunit mRNAs, while beta-estradiol caused
      significant increases in alpha3, beta3 and epsilon expression. Further analysis
      revealed differential regulation of alpha4, alpha5, epsilon and pi subunit
      expression. Plots of relative PCR density in progesterone-treated cells for
      alpha2 vs. alpha5, alpha5 vs. gamma3 and alpha2 vs. gamma3 showed correlation
      between samples, suggesting coordinate regulation. Both progesterone and estrogen
      nuclear receptor mRNAs were detected by RT-PCR, and 2 days but not 7 days
      estrogen exposure upregulated progesterone receptor mRNA. Gonadal steroid
      fluctuations regulate GABA(A) receptor subunit expression in NT2-N cells. Such
      changes, if observed in vivo, could affect seizure frequency.

PMID- 16000230
TI  - Therapeutic misconception in early phase gene transfer trials.
AB  - Many subjects in early phase clinical trials expect to benefit in some way from
      the research intervention. It is understandable that people hope for improvement
      in their condition, no matter what the evidence. Yet unreasonable expectation of
      medical benefit may reflect problems with informed consent: Investigators may not
      disclose clearly that direct medical benefit from an early phase experimental
      intervention is unlikely or impossible, or subjects may not appreciate the
      differences between treatment and research. This paper presents findings from
      recent interviews with researchers and subjects and analysis of consent forms in
      early phase gene transfer research, a cutting-edge technology often called 'gene
      therapy'. We use three variables to construct a composite measure of therapeutic
      misconception TM, tapping misconceptions about the purposes of early phase
      research and the potential for direct medical benefit in these trials. Our
      multivariate model demonstrates the importance of both subject- and study-level
      factors as predictors of this TM index: education, disease type, and
      communication by study personnel about the likelihood of benefit. We hope that
      this work will deepen the discussion of how to define and measure TM, and refine
      the specification of factors that are related to subjects' TM.

PMID- 16000231
TI  - Modulation of cytochrome P450 enzymes by organosulfur compounds from garlic.
AB  - Organosulfur compounds (OSCs) derived from garlic have been studied for the
      ability to inhibit experimental cancer in various animal models, primarily
      through modification of carcinogen detoxification enzymes, such as cytochrome
      P450 (CYP) enzymes. OSCs vary in structural and physical properties, and a
      detailed analysis of these properties has not been performed with respect to
      their ability of inhibit chemically-induced colon cancer development. Gastric
      intubation of rats with a single dose of 200 mg/kg diallyl sulfide (DAS), diallyl
      disulfide (DADS), and allyl methyl sulfide (AMS) decreased hepatic CYP2E1 protein
      by 45%, 25% and 47%, respectively, and this inhibition was sustained after 1, 4
      and 8 weeks of treatment by these compounds. Dipropyl sulfide (DPS), dipropyl
      disulfide (DPDS), propyl methyl sulfide (PMS) and S-allylcysteine (SAC) did not
      inhibit hepatic CYP2E1 protein expression, nor did any of the OSCs affect CYP2E1
      mRNA levels. A single dose of 200 mg/kg DAS and AMS increased hepatic CYP1A2
      protein (but not mRNA) by 282% and 70%, and DAS increased CYP1A1 protein levels
      by 684%. Daily treatment for 1, 4 and 8 weeks with 200 mg/kg DAS and AMS resulted
      in time-dependent increases in hepatic CYP1A1 and CYP1A2 protein levels to a
      maximum of 600% and 50% for DAS, and 1600% and 240% for AMS after 8 weeks. Dosing
      with 200 mg/kg of each of the OSCs used in this study increased hepatic CYP3A2
      protein levels at all time points. Dosing for 8 weeks with 200 mg/kg DAS, but not
      AMS or lower doses of DAS, induced bile duct obstruction and focal areas of
      necrosis. These results indicate that OSCs present in garlic, including DAS and
      AMS, may be beneficial in inhibiting chemically-induced colon cancer, but that
      longer dosing with higher concentrations of DAS may elicit minor hepatic
      toxicity.

PMID- 16000232
TI  - Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam,
      Dioscorea polygonoides.
AB  - In this study, three steroidal sapogenins (Delta3 diosgenin, diosgenin, and
      pennogenin) and the phytosterols, stigmasterol and beta-sitosterol were isolated
      from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood
      glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic
      rats were studied. The diabetic rats (fed supplemented and unsupplemented diets)
      lost weight significantly compared to the normal group. There was a significant
      increase in the activity of alpha-amylase in the proximal region of the small
      intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin.
      However, this did not result in increased fasting blood glucose. Instead,
      supplementation of the diet with bitter yam sapogenin extract significantly
      decreased fasting blood glucose compared to the diabetic group. Supplementation
      of the diet with bitter yam sapogenin extract or commercial diosgenin
      significantly reduced Na+-K+-ATPase activity in all three regions compared to the
      diabetic control group. Commercial diosgenin supplementation resulted in a
      significant increase in Ca2+ ATPase activity in proximal region compared to the
      diabetic control and bitter yam sapogenin extract groups. The effect of bitter
      yam sapogenin extract or commercial diosgenin on intestinal Na+-K+-ATPase
      activity could account for their hypoglycemic properties. However, there was
      adverse effect on the body weight.

PMID- 16000233
TI  - Isolation and structure elucidation of phenolic antioxidants from Tamarind
      (Tamarindus indica L.) seeds and pericarp.
AB  - Although it is already known that Tamarind (Tamarindus indica L.) seeds contain
      phenolic substances, the individual components of the seeds have not been fully
      identified and quantitated, and in the case of Tamarind pericarp not reported.
      Therefore, major polyphenolic compounds were extracted using organic solvents and
      the metabolites were isolated by semi-preparative high performance liquid
      chromatography. Their structures were elucidated by liquid chromatography
      electrospray-ionisation-mass spectrometry (LC-ESI-MS), nano-electrospray
      ionisation mass spectrometry (ESI-MS), and where possible by gas chromatography
      mass spectrometry (GC-MS) and 1H and 13C NMR. Quantitative analysis of
      polyphenolic compounds in Tamarind seeds and pericarp was conducted by analytical
      high performance liquid chromatography (HPLC), calculated against standard curves
      of authentic compounds. The yields of total phenolic compounds after Soxhlet
      extraction with methanol were 6.54 and 2.82 g/kg (dry weight) in the seeds and
      pericarp respectively. The profile (%) of polyphenolics in Tamarind pericarp was
      dominated by proanthcyanidins (73.4) in various forms (+)-catechin (2.0),
      procyanidin B2 (8.2), (-)-epicatechin (9.4), procyanidin trimer (11.3),
      procyanidin tetramer (22.2), procyanidin pentamer (11.6), procyanidin hexamer
      (12.8) along with taxifolin (7.4), apigenin (2.0), eriodictyol (6.9), luteolin
      (5.0) and naringenin (1.4) of total phenols, respectively. The content of
      Tamarind seeds comprised only procyanidins, represented (%) mainly by oligomeric
      procyanidin tetramer (30.2), procyanidin hexamer (23.8), procyanidin trimer
      (18.1), procyanidin pentamer (17.6) with lower amounts of procyanidin B2 (5.5)
      and (-)-epicatechin (4.8). Extraction of Tamarind pericarp and seeds using
      acetone:methanol:acetic acid gave only procyanidin oligomers, but in much higher
      yield and variety. The antioxidant capacities of the Soxhlet methanolic extracts
      were determined, and indicates that Tamarind may be an important source of cancer
      chemopreventive natural products in tropical regions.

PMID- 16000234
TI  - Efficacy of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and diphenyl diselenide
      on cadmium induced testicular damage in mice.
AB  - The deleterious effect of acute cadmium-intoxication in mice testes was
      evaluated. Animals received a single dose of CdCl2 (2.5 or 5 mg/kg,
      intraperitoneally) and a number of toxicological parameters in mice testes were
      examined, such as delta-aminolevulinic acid dehydratase (delta-ALA-D) activity,
      lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the
      parameters that indicate tissue damage such as plasma alanine aminotransferase
      (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also
      determined. Thus, a possible protective effect of 2,3-dimercapto-1-propane
      sulfonic acid (DMPS) and diphenyl diselenide (PhSe)2 were studied. The results
      demonstrated an inhibition of delta-ALA-D activity, a reduction of ascorbic acid
      and an increase of lipid peroxidation induced by cadmium, indicating testes
      damage. Furthermore, we observed an increase of plasma LDH, AST and ALT
      activities. DMPS (400 mol/kg) and (PhSe)2 (100 micromol/kg) partially protected
      from the inhibitory effect of 2.5 mg/kg CdCl2 on delta-ALA-D and from the
      increase of TBARS (thiobarbituric acid reactive species) levels. (PhSe)2 therapy
      was effective in ameliorate ascorbic acid content when the cadmium dose was 2.5
      mg/kg. Treatment with DMPS and (PhSe)2, individually or combined, was inefficient
      in reducing cadmium-induced plasma LDH and ALT activity increase. The use of
      combined therapy (DMPS plus (PhSe)2) proved to be efficient in decreasing cadmium
      levels in testes and in ameliorating plasma AST activity from animals that
      received the highest dose of cadmium.

PMID- 16000235
TI  - The plant lignans matairesinol and secoisolariciresinol administered to Min mice
      do not protect against intestinal tumor formation.
AB  - The lignans matairesinol (MAT) and secoisolariciresinol (SECO) were fed to Min
      mice at 0.02% (w/w) in diet to study their effects on intestinal tumor
      development. The mean number (67 vs. 51, P=0.052) and size (1.4 vs. 1.2 mm,
      P=0.011) of tumors in the MAT group was elevated when compared with the control
      group. Tumor formation of the SECO group did not differ from the control group.
      Intake of MAT increased the level of both MAT and enterolactone in the plasma
      while SECO feeding increased SECO, enterodiol, and enterolactone (P=0.001). These
      results showed that MAT or SECO do not prevent intestinal carcinogenesis in Min
      mice and that MAT may have adverse effects.

PMID- 16000236
TI  - Pig tissues express a catalytically inefficient 25-kDa thiamine triphosphatase:
      insight in the catalytic mechanisms of this enzyme.
AB  - Thiamine triphosphate (ThTP) is found in most organisms and may be an
      intracellular signal molecule produced in response to stress. We have recently
      cloned the cDNA coding for a highly specific mammalian 25-kDa thiamine
      triphosphatase. The enzyme was active in all mammalian species studied except
      pig, although the corresponding mRNA was present. In order to determine whether
      the very low ThTPase activity in pig tissues is due to the absence of the protein
      or to a lack of catalytic efficiency, we expressed human and pig ThTPase in E.
      coli as GST fusion proteins. The purified recombinant pig GST-ThTPase was found
      to be 2-3 orders of magnitude less active than human GST-ThTPase. Using site
      directed mutagenesis, we show that, in particular, the change of Glu85 to lysine
      is responsible for decreased solubility and catalytic activity of the pig enzyme.
      Immunohistochemical studies revealed a distribution of the protein in pig brain
      very similar to the one reported in rodent brain. Thus, our results suggest that
      a 25-kDa protein homologous to hThTPase but practically devoid of enzyme activity
      is expressed in pig tissues. This raises the possibility that this protein may
      play a physiological role other than ThTP hydrolysis.

PMID- 16000237
TI  - Phenanthridine alkaloids from Zanthoxylum madagascariense.
AB  - Four benzo[c]phenanthridine alkaloids have been isolated from the stem bark of
      Zanthoxylum madagascariense. These compounds were identified by extensive use of
      NMR spectroscopy.

PMID- 16000238
TI  - A novel Spiroplasma pathogen causing systemic infection in the crayfish
      Procambarus clarkii (Crustacea: Decapod), in China.
AB  - A novel disease of crayfish Procambarus clarkii appeared in the summer of 2004 in
      freshwater aquaculture in Jiangsu province of China. Light and transmission
      electron microscopy (TEM), molecular biological methods and in vitro culture were
      used to identify the pathogen. The agent was unique in having a helical
      morphology and rotary motility as observed by phase-contrast light microscopy and
      was found in haemolymph, muscles, nerves and connective tissues by smear method
      and TEM. Ultra-thin sections under TEM revealed the wall-free membrane of the
      microbe. The agent could pass through membrane filters with pores 220 nm in
      diameter and was cultivated in vitro in M1D medium. 16S rDNA of the crayfish
      pathogen was amplified by PCR using primers specific for Spiroplasma-specific 16S
      rDNA. The resultant 271bp PCR product showed 99% identity with Spiroplasma mirum
      16S rDNA, having a close relationship with the spiroplasma from the Chinese
      mitten crab Eriocheir sinensis. This is the second time a spiroplasma has been
      found in a freshwater crustacean. The 271bp PCR product was also amplified from
      the bottom mud in the ponds associated with the disease. The PCR molecular method
      is an effective way to detect spiroplasma in freshwater environment. The results
      from this study are significant in expanding the host range of spiroplasma and
      freshwater ecology.

PMID- 16000239
TI  - Helicobacter pylori induce neutrophil transendothelial migration: role of the
      bacterial HP-NAP.
AB  - Continuous recruitment of neutrophils into the inflamed gastric mucosal tissue is
      a hallmark of Helicobacter pylori infection in humans. In this study, we examined
      the ability of H. pylori to induce transendothelial migration of neutrophils
      using a transwell system consisting of a cultured monolayer of human endothelial
      cells as barrier between two chambers. We showed for the first time that live H.
      pylori, but not formalin-killed bacteria, induced a significantly increased
      transendothelial migration of neutrophils. H. pylori conditioned culture medium
      also induced significantly increased transendothelial migration, whereas heat
      inactivated culture filtrates had no effect, suggesting that the chemotactic
      factor was proteinaceous. Depletion of H. pylori-neutrophil activating protein
      (HP-NAP) from the culture filtrates resulted in significant reduction of the
      transmigration. Culture filtrates from isogenic HP-NAP deficient mutant bacteria
      also induced significantly less neutrophil migration than culture filtrates
      obtained from wild-type bacteria. HP-NAP did not induce endothelial cell
      activation, suggesting that HP-NAP acts directly on the neutrophils. In
      conclusion, our results demonstrate that secreted HP-NAP is one of the factors
      resulting in H. pylori induced neutrophil transendothelial migration. We propose
      that HP-NAP contributes to the continuous recruitment of neutrophils to the
      gastric mucosa of H. pylori infected individuals.

PMID- 16000240
TI  - A novel strategy for the isolation and identification of environmental
      Burkholderia cepacia complex bacteria.
AB  - The purpose of this study was to develop a novel strategy for the isolation and
      identification of Burkholderia cepacia complex bacteria from the home environment
      of cystic fibrosis (CF) patients. Water and soil samples were enriched in a broth
      containing 0.1% l-arabinose, 0.1% l-threonine, and a mixture of selective agents
      including 1 microgml(-1) C-390, 600U ml(-1) polymyxin B sulfate, 10 microgml(-1)
      gentamycin, 2 microgml(-1) vancomycin and 10 microgml(-1) cycloheximide. On
      selective media (consisting of the same components as above plus 1.8% agar),
      several dilutions of the enrichment broth were inoculated and incubated for 5
      days at 28 degrees C. Isolates with different randomly amplified polymorphic DNA
      patterns were inoculated in Stewart's medium. Putative B. cepacia complex
      bacteria were confirmed by means of recA PCR and further identified by HaeIII
      recA restriction fragment length polymorphism analysis. Our results suggest that
      these organisms may be more widespread in the home environment than previously
      assumed and that plant associated soil and pond water may be reservoirs of B.
      cepacia complex infection in CF patients.

PMID- 16000241
TI  - Characterization of Listeria monocytogenes isolates from food animal clinical
      cases: PFGE pattern similarity to strains from human listeriosis cases.
AB  - Twenty-one isolates of Listeria monocytogenes from food animal clinical cases
      that involved meningitis or meningoencephalitis, encephalitis, mastitis and
      abortion were characterized by serotyping and pulsed-field gel electrophoresis
      (PFGE) in order to improve our understanding of the genetic links between
      individual strains and strains recovered from human listeriosis cases. Results
      showed that five of the isolates were serotype 1/2a, six were 1/2b, nine were 4b,
      and one was untypeable. A caprine, two bovine and an ovine brain isolate shared
      identical PFGE patterns indicating that strains of L. monocytogenes are not host
      specific. Other isolates exhibited distinct patterns that were not shared,
      indicating a genetic diversity. Dendrogram analysis revealed that PFGE patterns
      of the isolates clustered primarily according to serotype. We compared the PFGE
      types obtained for these isolates with PFGE types for human clinical isolates
      present in the CDC national PulseNet database. Six (29%) of the twenty-one
      strains had patterns that were indistinguishable from pathogenic human isolates
      in the database. Our observations offer preliminary evidence that food animals
      could be significant reservoirs of L. monocytogenes that lead to human infections
      and support the inclusion of PFGE patterns of veterinary clinical isolates in the
      national PulseNet database for increased surveillance.

PMID- 16000242
TI  - Molecular phylogenetic and isotopic evidence of two lineages of chemoautotrophic
      endosymbionts distinct at the subdivision level harbored in one host-animal type:
      the genus Alviniconcha (Gastropoda: Provannidae).
AB  - The hydrothermal-vent gastropod Alviniconcha hessleri from the Alice Springs deep
      sea hydrothermal field in the Mariana Back-Arc Basin in the Western Pacific
      houses an intracellular bacterial endosymbiont in its gill. Although enzymatic
      analysis has revealed that the endosymbiont is a sulfur-oxidizing chemoautotroph
      using the Calvin-Benson cycle for the fixation of carbon dioxide, the
      phylogenetic affiliation of, and the trophic relationship of A. hessleri with,
      the chemoautotrophic endosymbiont remains undetermined. A single 16S rRNA gene
      sequence was obtained from the DNA extract of the gill, and phylogenetic analysis
      placed the source organism within the lineage of the gamma subdivision of the
      Proteobacteria that consists of many chemoautotrophic endosymbionts of marine
      invertebrates. Fluorescence in situ hybridization analysis showed the bacterium
      densely colonizing the gill filaments. The fatty acid profile of the symbiont
      free mantle contains the high level of the 16:1 fatty acid originating from the
      endosymbiont, which indicates that the endosymbiont cells are digested by, and
      incorporated into, the host. Compound-specific carbon isotopic analysis revealed
      that fatty acids from the gastropod tissues are all (13)C-depleted relative to
      the gastropod biomass. This fractionation pattern is consistent with
      chemoautotrophy based on the Calvin-Benson cycle and subsequent fatty-acid
      biosynthesis from (13)C-depleted acetyl coenzyme A. The results from the present
      study are clearly different from those from our previous study for A. aff.
      hessleri from the Indian Ocean that harbors a chemoautotrophic endosymbiont
      belonging to the epsilon subdivision of the Proteobacteria, which mediates the
      reductive tricarboxylic acid cycle for carbon fixation. Thus, it is concluded
      here that two lineages of chemoautotrophic bacteria, phylogenetically distinct at
      the subdivision level, occur as the primary endosymbiont in one host-animal type,
      which is unknown for the other metazoans.

PMID- 16000244
TI  - Use of the skin protection assay in experimental syphilis to assess protective
      immunity against a specific Treponema pallidum surface epitope.
AB  - We have recently shown that a monoclonal antibody, designated M131, that binds a
      surface phosphorylcholine epitope on Treponema pallidum possesses complement
      dependent killing activity and confers partial protection in rabbits following
      passive immunization (Blanco et al., 2005, Infect. Immun. 73:3083-3095). In this
      study, the protective potential of M131 was further tested using the rabbit skin
      protection assay of Titus and Weiser. Both M131 and infection-derived immune
      rabbit serum resulted in significant lesion delays corresponding to at least a
      90% reduction of the treponemal challenge inoculum. The skin protection assay
      provides a way to assess the protective potential of specific immunogens while
      using far less antibody than in passive immunization protocols.

PMID- 16000243
TI  - High diversity of endophytic fungi from the pharmaceutical plant, Heterosmilax
      japonica Kunth revealed by cultivation-independent approach.
AB  - Heterosmilax japonica Kunth is well recognized for its diuretic effects in China.
      However, little is known about its endophytic fungi. In this study, microbial
      communities inhabiting the stems of H. japonica in spring and summer were
      investigated by light microscopy and cultivation-independent approaches, such as
      RFLP analysis and sequencing of rDNA ITS library. Molecular phylogenetic analysis
      showed that a broad spectrum of fungi, including Mycosphaerella, Phomopsis,
      Aureobasidium, Cladosporium, Glomerella, Botryosphaeria, Guignardia, is able to
      colonize the plants internally. Particularly, several rDNA sequences determined
      in this study like YJ4-61 are not specifically affiliated with any currently
      documented fungal sequences in the public database. Several sequence types, such
      as YJ4-9 and YJ4-70, are significantly similar to some uncultured environmental
      samples. Furthermore, our result also showed that the samples collected in spring
      harbored more abundant endophytic populations than that in summer, implying a
      seasonal fluctuation for the endophytes in H. japonica.

PMID- 16000245
TI  - Identification of an AraC-like regulator gene required for induction of the 78
      kDa ferrioxamine B receptor in Vibrio vulnificus.
AB  - We previously reported that the 78-kDa outer membrane receptor for ferrioxamine B
      is induced in iron-starved Vibrio vulnificus cells when desferrioxamine B was
      supplied exogenously. Based on its N-terminal amino acid sequence, a candidate
      gene for the ferrichrome B receptor was detected in the V. vulnificus CMCP6
      genomic database. Here, two contiguous genes, named desR and desA, encoding a
      member of the AraC family of transcriptional activators and the ferrioxamine B
      receptor, respectively, were cloned from V. vulnificus M2799 and characterized.
      Primer extension analysis mapped the iron-regulated transcription initiation
      sites for desR and desA, and demonstrated involvement of desferrioxamine B in the
      induction of desA transcription. Insertion mutation of desR resulted in no
      production of DesA under iron-limiting conditions even in the presence of
      desferrioxamine B. The DesA production under the same conditions was restored to
      wild-type levels when the desR mutant was complemented with desR in trans. These
      results suggest that the desR gene is required for desferrioxamine B-inducible
      production of DesA in iron-starved cells.

PMID- 16000246
TI  - Differential expression of the LGI and SLIT families of genes in human cancer
      cells.
AB  - The LGI and SLIT genes have a distinctive leucine-rich repeat motif in the N
      terminal end of the protein which is indicative of either receptor function or an
      interaction with the extracellular matrix. Members of the LGI and SLIT family of
      genes have been implicated in specific cancers and have been suggested to have a
      restricted pattern of expression in normal cells. To investigate the extent and
      distribution of the expression of these genes in cancer cells we have analyzed
      their expression levels in a range of tumor cell types. Different tumor types
      appear to hold a preference for the specific members of the families which are
      expressed. Differential expression between cell lines, from the same tumor type,
      implies a role for inactivation and reactivation of these genes during
      tumorigenesis. The detailed characterization of the expression pattern in these
      tumor cells offers the opportunity to perform a functional analysis of these
      individual genes.

PMID- 16000247
TI  - Effect of cadmium on gene expression in the liverwort Lunularia cruciata.
AB  - Bryophytes are valuable bioaccumulators, because they have high absorbing and ion
      exchange capacities. Cadmium (Cd) is a heavy metal naturally present in soil; it
      is non-essential and highly toxic to most organisms, having toxicity 2 to 20
      times higher than many other heavy metals. The presence of elevated levels of Cd
      ions triggers a wide range of cellular responses including changes in gene
      expression and synthesis of metal-detoxifying peptides. To investigate the
      ability of Cd to affect gene transcription, the messenger RNA (mRNA) differential
      display technique was applied to the identification and isolation of genes whose
      transcription was altered in cultured Lunularia cruciata plants that were grown
      in the presence of cadmium salts. Four genes whose mRNA levels significantly
      changed in response to cadmium exposure were isolated and identified. The first
      gene identified in our analysis is up-regulated by Cd: it encodes the enzyme
      cystathionine gamma-synthase. The other genes are down-regulated by cadmium.
      These genes encode a methyltransferase, a tyrosine phosphatase and the EST 408 of
      the diatom Fragilariopsis cylindrus, whose function is unknown. Our findings
      demonstrate the usefulness of mRNA differential display technique for the
      detection of plant metabolic pathways affected by cadmium stress.

PMID- 16000248
TI  - Prestin-dependent and prestin-independent motility of guinea pig outer hair
      cells.
AB  - The motile response of isolated guinea pig outer hair cells (OHCs) was
      investigated using a combination of whole-cell patch clamp recording and
      continuous video image analysis. OHC's length, width, and area were measured from
      video images and the cell volume estimated from these values. Morphological data
      was then correlated with electrophysiological recordings of whole-cell current,
      membrane potential and voltage-dependent non-linear capacitance. Electromotility
      was evoked either by manipulating the membrane potential under voltage-clamp
      conditions or by exposing OHCs to high K+ solutions. Other motile responses were
      investigated in voltage-clamp experiments at constant holding potential, or
      exposing OHCs to solutions that did not affect the membrane potential. We found
      that electrical stimulation evoked voltage-dependent changes in OHC's length,
      width and area but not in cell volume regardless of the time course of
      stimulation. Moreover, changes in cell area were always associated with both
      voltage-dependent motility and non-linear capacitance, suggesting prestin
      dependency. In contrast, voltage-independent motile responses at constant
      membrane potential, which are presumed to be prestin-independent, were associated
      with changes in cell length, width and volume without significant changes in
      area. Area measurements, then, become a tool to investigate the simultaneous
      occurrence of both prestin-dependent and prestin-independent OHC motilities, and
      for evaluating the individual contribution of each mechanism to the total cell
      movement.

PMID- 16000249
TI  - Differential effects of cyclodextrins and derivatives on the biological behavior
      of the myocardial perfusion imaging agent 99mTcN-NOET.
AB  - In addition to improving drug solubilization, cyclodextrins (CDs) also affect the
      biological behavior of the included compound. We evaluated the effects of two
      natural CDs beta-CD and gamma-CD, and six beta-CD derivatives, Dimeb, Trimeb,
      SBb, 2-HP, 6AD, and 6 MTU on the biological behavior of (99m)TcN-NOET, a
      technetium-99m-labeled, lipophilic compound readily detectable through
      radioactivity assessment. Determination of CDs' affinities for (99m)TcN-NOET
      indicated that the cavity size of gamma-CD was not suitable for (99m)TcN-NOET
      inclusion, and that beta-CD derivatization mostly resulted in decreased CDs
      affinities for (99m)TcN-NOET to various extents compared with the natural beta
      CD. In vitro and ex vivo experiments performed on newborn rat cardiomyocytes and
      isolated perfused rat hearts, respectively, showed 1.7- and 2.3-fold maximal
      differences in (99m)TcN-NOET cellular and tissue activities. Regression analyzes
      indicated no significant correlation between these observed biological
      differences and the affinities of the eight CDs tested for (99m)TcN-NOET or for
      cellular membranes. In conclusion, CD derivatization often resulted in impaired
      affinity of the derivatives for the lipophilic compound (99m)TcN-NOET. Moreover,
      the in vitro and ex vivo biological behavior of (99m)TcN-NOET was greatly
      affected depending on the CD used for inclusion of the tracer.

PMID- 16000250
TI  - Primary angiosarcoma of the breast associated Kasabach-Merritt syndrome during
      pregnancy.
AB  - Primary angiosarcoma of the breast is a rare aggressive tumour of unknown
      etiology. A frequent clinical presentation is a painful palpable smooth mass or
      diffuse enlargement of the breast without a palpable mass but with purple
      discolouration of the overlying skin with apparent bruising. An uncommon clinical
      presentation of an angiosarcoma is spontaneous bleeding due to disseminated
      intravascular coagulation (DIC) by consumption coagulopathy, known as the
      Kasabach-Merritt syndrome. Imaging characteristics of a breast angiosarcoma are
      limited to a few radiological reports. We report a case of a young pregnant woman
      with a bleeding angiosarcoma of the breast and associated Kasabach-Merritt
      syndrome and describe the sonographic and MRI findings.

PMID- 16000251
TI  - Mammographic densities and circulating hormones: a cross-sectional study in
      premenopausal women.
AB  - Progestogens appear to influence breast density more than estrogens in
      postmenopausal women taking hormone replacement therapy (HRT), but little is
      known about the effect of circulating hormones on mammographic density among
      premenopausal women. This cross-sectional study explores the relationship of body
      weight and sex steroids with breast density. Luteal serum samples were analyzed
      for progesterone, estrone, estradiol, and sex hormone-binding globulin (SHBG).
      Mammograms were assessed for density using a computer-assisted method. We
      performed mediation tests using multiple linear regression models. Significant
      associations of SHBG and estradiol with percentage density disappeared after
      adjustment for body weight and other covariates, whereas the relationship between
      progesterone and breast density remained borderline significant. The mediation
      tests indicated that progesterone has a direct and an indirect effect on
      mammographic density. Our finding that progesterone shows a stronger association
      with percentage of mammographic density than estrogen agrees with clinical
      reports describing denser mammographic patterns among women taking HRT, although
      these women differ in menopausal status.

PMID- 16000252
TI  - X-ray microtomography of 410 million-year-old optic capsules from placoderm
      fishes.
AB  - The structure of two small ossified optic capsules from mid-Palaeozoic placoderm
      fishes has been revealed in fine detail, by the use of X-ray microtomography
      analysis and 3D visualisation software. These two specimens are 410 million-year
      old; they were collected from an Early Devonian (Lochkovian) limestone in central
      New South Wales, and are the oldest known optic capsules from jawed fishes. The
      capsules show attachment areas for seven extrinsic eye muscles, rather than the
      six until recently deemed universal for gnathostomes. The analysis also revealed
      structures within the ossified cartilage which covered the medial surface of the
      eyeball, including nerve tracts, vascular canals, and possibly a choroid rete
      mirabile.

PMID- 16000253
TI  - Hemodynamic and metabolic responses to activation, deactivation and epileptic
      discharges.
AB  - To investigate the coupling between the hemodynamic and metabolic changes
      following functional brain activation as well as interictal epileptiform
      discharges (IEDs), blood oxygenation level dependent (BOLD), perfusion and oxygen
      consumption responses to a unilateral distal motor task and interictal
      epileptiform discharges (IEDs) were examined via continuous EEG-fMRI. Seven
      epilepsy patients performed a periodic (1 Hz) right-hand pinch grip using
      approximately 8% of their maximum voluntary contraction, a paradigm previously
      shown to produce contralateral MI neuronal excitation and ipsilateral MI neuronal
      inhibition. A multi-slice interleaved pulsed arterial spin labeling and T(2)*
      weighted gradient echo sequence was employed to quantify cerebral blood flow
      (CBF) and BOLD changes. EEG was recorded throughout the imaging session and
      reviewed to identify the IEDs. During the motor task, BOLD, CBF and cerebral
      metabolic rate of oxygen consumption (CMR(O(2))) signals increased in the contra-
      and decreased in the ipsilateral primary motor cortex. The relative changes in
      CMR(O(2)) and CBF were linearly related, with a slope of 0.46 +/- 0.05. The ratio
      of contra- to ipsilateral CBF changes was smaller in the present group of
      epilepsy patients than in the healthy subjects examined previously. IEDs produced
      both increases and decreases in BOLD and CBF signals. In the two case studies for
      which the estimation criteria were met, the coupling ratio between IED-induced
      CMR(O(2)) and CBF changes was estimated at 0.48 +/- 0.17. These findings provide
      evidence for a preserved coupling between hemodynamic and metabolic changes in
      response to both functional activation and, for the two case studies available,
      in response to interictal epileptiform activity.

PMID- 16000254
TI  - Regulation of membrane lipid bilayer structure during salinity adaptation: a
      study with the gill epithelial cell membranes of Oreochromis niloticus.
AB  - A significant variation in the membrane fluidity (as assessed by DPH-fluorescence
      polarisation) and membrane lipid bilayer composition is noticed in the
      subcellular membranes of the gill epithelial cells of Oreochromis niloticus due
      to exposure of the fish to 1% saline water for 1 month. Also, a 70% enhanced
      activity of Na(+)-K(+)-ATPase in plasma membranes and a 2.5-fold increase of
      glucose-6-phosphate dehydrogenase in microsomal membranes are recorded in the
      treated fish. The changed membrane structure and fluidity along with the changed
      enzymatic activity of Na(+)-K(+)-ATPase help the influx the Na(+) rather than the
      efflux of K(+) through the gill epithelial cells during salinity adaptation.

PMID- 16000255
TI  - The role of electromyography in the management of the brachial plexus palsy of
      the newborn.
AB  - Despite being the foremost examination in the management of traumatic nerve
      damage electromyography (EMG) has an uncertain and ill-defined role in the
      investigation of brachial plexus palsy of the newborn (BPPN). This may be because
      EMG, which is used most commonly several months after birth, fails to answer
      adequately two of the most important questions posed by this condition: its
      aetiology and the likely prognosis. In this review, we contend that EMG has
      important contributions to the solution of both of these questions but only if
      the timing of the investigation is altered. Used early on in the first few days
      after birth, EMG can separate the rare palsies that occurred during the
      intrauterine period from those caused by events at the time of birth, and thus
      have an important role in directing the investigations of the aetiology more
      appropriately. EMG alone would still not be able to determine which of the
      perinatal events were responsible. If the EMG is then repeated before
      reinnervation complicates interpretation, it seems probable that it would
      identify accurately those cases, where neurotmesis and avulsion have occurred,
      much earlier than 3 months of age, the crucial age in the clinical assessment of
      BPPN for consideration for surgery. This might have very important implications
      for the future directions of treatment.

PMID- 16000256
TI  - Locating chronically implanted subdural electrodes using surface reconstruction.
AB  - OBJECTIVE: To determine the accuracy of locating subdural electrodes by means of
      3-D surface rendering of CT scans. METHODS: Open source software has been
      developed and posted on the web which segments the electrodes into 3-D surfaces
      and allows their 3-D locations to be exported to other EEG analysis programs. The
      accuracy of the technique was determined by studying 410 subdural electrodes
      implanted in four epilepsy patients. Accuracy was determined by comparing the
      locations from the rendering analysis to the locations of the same electrodes
      determined by conventional analysis of their appearance on individual CT slices.
      RESULTS: The average accuracy of a study of 410 electrodes imaged in four
      patients repeated two times by three observers was 0.91 (+/- 0.41) mm, with a
      maximum error of 3.3 mm, about half of the diameter of an electrode. CONCLUSIONS:
      The location of subdural electrodes can easily and quickly be determined within
      high-resolution CT scans through the use of 3-D rendering. SIGNIFICANCE: This
      relatively fast and easy method for determining the location of subdural
      electrodes should facilitate their use in both clinical and research
      investigations.

PMID- 16000258
TI  - Trusting in or breaking with convention: towards a renaissance of principal
      components analysis in electrophysiology.

PMID- 16000257
TI  - Sensory gating in the human hippocampal and rhinal regions.
AB  - OBJECTIVE: The objective of this work was to ascertain if sensory gating can be
      demonstrated within the human medial temporal lobe. METHODS: Eight patients with
      intractable epilepsy with depth electrodes implanted in the medial temporal lobe
      for pre-surgery evaluation underwent evoked response recording to auditory paired
      stimuli (S1-S2). Each of the eight subjects had a diagnosis of left medial
      temporal lobe epilepsy (MTLE). RESULTS: Data from the non-focal right hippocampi
      revealed a large negative response on S1 (starting at about 190 ms and lasting
      for approximately 300 ms from stimulus onset). Rhinal region recordings revealed
      a positive response (starting at about 240 ms with a rapid incline, followed by a
      long-lasting decline). A significant attenuation of both responses to S2 stimuli
      was observed. CONCLUSIONS: Data are suggestive of an involvement of the human
      medial temporal lobe in the processing of simple auditory information which
      occurs in a time frame later than the neocortical auditory evoked components. The
      exact role of these anatomical structures in the sensory gating process remains
      to be defined. SIGNIFICANCE: This study provides the first evidence of an
      activation of the rhinal cortex after simple auditory stimulation and provides
      new evidence that the activation of the medial temporal lobe structures occurs at
      a later stage than that of the neocortex.

PMID- 16000259
TI  - New clues to accrue on neutropenia in rheumatoid arthritis.

PMID- 16000260
TI  - Sympathetically induced renal vasoconstriction during stimulation of
      mesencephalic locomotor region in rats.
AB  - Central command, which is a neural drive originating in the brain during
      exercise, regulates the sympathetic nervous system and evokes cardiovascular
      responses to exercise. To examine the role of the central command on sympathetic
      regulation of renal circulation, we compared responses in renal cortical blood
      flow and vascular conductance to electrical stimulation of mesencephalic
      locomotor region (MLR) for 30 s in decerebrate and paralyzed rats between renal
      nerves that were intact (n=8) and denervated (n=8). In rats with renal nerves
      intact, stimulation of the MLR at 40 microA current intensity significantly
      (p<0.05) decreased renal cortical blood flow (-17+/-5%, means+/-S.E.M.) and
      vascular conductance (-43+/-4%) and the decrease in renal vascular conductance
      was dependent on current intensity (between 20 and 60 microA). In renal
      denervated rats, in contrast, there were no significant changes in either renal
      cortical blood flow or vascular conductance during stimulation at all current
      intensities. In a subset of rats (n=8), the response in renal sympathetic nerve
      activity to 30 s stimulation of the MLR was investigated. Stimulation of the MLR
      significantly increased renal sympathetic nerve activity (+57+/-14% at 40 microA)
      and the response was dependent on current intensity (between 20 and 60 microA).
      These data provide evidence that central command induces renal vasoconstriction
      by increasing sympathetic activity, depending on central command intensity.

PMID- 16000261
TI  - Electrochemistry of marmatite-carbon paste electrode in the presence of bacterial
      strains.
AB  - The electrochemical behaviors of a marmatite-carbon paste electrode with the
      chemical leaching of Fe3+ ions, or the microbial leaching using Acidithiobacillus
      ferrooxidans, were compared. The cyclic voltammograms of the electrode in the
      presence and absence of bacterial strains showed that the leaching process of
      marmatite was carried out by the different reactions occurring in the interface
      of the marmatite electrode-leach liquid. The polarization currents of the
      electrode under the differently applied potentials suggested that the microbial
      leaching of marmatite could be accelerated by the applied potential. The SEM
      observations indicated that the corrosion pits formed in the electrode surface
      were similar to the attached bacterial cells in shape and size, other than that
      by the chemical leaching of Fe3+ ions. The contact leaching of the attached cells
      on the mineral substrate played an important role on the dissolution of marmatite
      in addition to the chemical leaching of Fe3+ ions.

PMID- 16000262
TI  - Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with
      [99mTc], [111In], [153Sm] and [188Re] on bone compartments: verification of the
      pre vivo model?
AB  - INTRODUCTION: Although the first polyphosphonates (PP) were introduced to nuclear
      medicine as bone imagers in the early 70s, mechanisms involved in uptake still
      remain speculative. Controversies range from adsorption onto the mineral phase
      with disputed binding to the organic phase, over incorporation into the
      mineralisation process to a combination of both mechanisms. Other factors such as
      solubility of the complex, concentration of ligand or effects of the radionuclide
      have also been discussed as possible parameters influencing bone uptake.
      Therefore, the present work aimed to verify the recently presented pre vivo model
      which was developed to rate the influence of various factors on the binding of
      differently radiolabelled PP and [18F]-fluoride on synthetic bone matrix.
      METHODS: Radiolabelled polyphosphonates and [18F]-fluoride were added to a vial
      containing lyophilised and milled spongiosa (Sp) or cortical bone (Co) in Hank's
      Balanced Salt Solution. After incubation, the radioactivity was measured in the
      gamma-counter before and after filtration. The percentage of irreversibly bound
      radioactivity was calculated. Same experiments were performed after
      decalcification of Sp and Co with hydrochloric acid. RESULTS: Descriptively,
      [111In] increases the uptake of EDTMP in each case compared to similarly prepared
      [(99m)Tc]-analogues: [111In]-EDTMP > [(99m)Tc]-EDTMP, [111In]-/In-EDTMP >
      [(99m)Tc]-/In-EDTMP and [111In]-/Re-EDTMP > [(99m)Tc]-/Re-EDTMP. [188Re]-EDTMP
      shows higher binding than the carrier-added analogue, contradicting recent in
      vivo findings of [(188)Re]-PP. However, our findings on human matrix are
      consistent with those of a previous study using artificial bone material. Binding
      on decalcified tissue was very low (PP) to moderate ([18F]-fluoride) and
      reversible. Remarkable is also the unrivalled high uptake of [18F]-fluoride,
      showing no reduced uptake on Co and Sp as compared to hydroxyapatite (HA) and
      amorphous calcium phosphate (ACP). CONCLUSION: The binding of the evaluated bone
      seekers on these human bone matrices follows a comparable pattern as on
      artificial bone. The present study substantiates the fact that binding
      predominantly occurs on the inorganic compartment of bone. The best correlation
      was found between HA and Co. Therefore, HA can serve as a matrix for
      representative binding studies.

PMID- 16000263
TI  - The Oral Fluid MEMS/NEMS Chip (OFMNC): diagnostic and translational applications.
AB  - The ability to monitor health status, disease onset and progression, and
      treatment outcome through non-invasive means is a most desirable goal in health
      care promotion and delivery. There are three prerequisites for this goal to be
      realized: specific biomarkers associated with a health or disease state, a non
      invasive approach to detect and monitor the biomarkers, and the technologies to
      discriminate between and among the biomarkers. We present a roadmap to achieve
      these goals using oral fluids as the diagnostic medium to scrutinize the health
      and/or disease status of individuals. This is an ideal opportunity to bridge
      state-of-the-art micro-/nano-electromechanical system (MEMS/NEMS) sensors to oral
      fluid for diagnostic applications. As the "mirror of body", oral fluid is a
      perfect medium to be explored for health and disease surveillance. The
      translational applications and opportunities are enormous.

PMID- 16000264
TI  - Do automatic reactions elicited by thoughts of romantic partner, mother, and self
      relate to adult romantic attachment?
AB  - Three studies tested the expectation that automatic reactions elicited by the
      mental representation of one's current romantic partner, mother, and self relate
      to adult romantic attachment. Adult romantic attachment was assessed using
      multiple measures, and individual differences in automatic reactions were
      assessed by the Implicit Association Test (IAT). Studies 1 and 2 showed that
      automatic reactions elicited by thoughts of current romantic partner, but not by
      thoughts of self, were related to adult romantic attachment assessed at a
      specific (i.e., within one's current romantic relationship) and general level
      (i.e., across all romantic relationships). The pattern of results was stronger
      among individuals identified as attachment-schematic. Studies 2 and 3 showed that
      automatic reactions elicited by thoughts of one's mother were related to adult
      romantic attachment assessed at a general level. In all three studies, results
      did not differ depending on how adult romantic attachment was conceptualized
      (four styles vs. two dimensions).

PMID- 16000265
TI  - Generalized and specific attachment representations: unique and interactive roles
      in predicting conflict behaviors in close relationships.
AB  - The authors expected that associations between the representations individuals
      possess regarding romantic partners and their conflict behavior would be
      moderated by generalized attachment representations (GAR). To test this premise,
      college students (N =130) were administered two attachment measures and were
      observed during conflict negotiation with their partners. The Relationship Styles
      Questionnaire assessed specific representations regarding partners and GAR were
      measured by the Adult Attachment Interview. The relationship between romantic
      partner representations and conflict tactics were dependent on GAR. Individuals
      who possessed secure GAR generally displayed good conflict management skills,
      regardless of their attachment representations regarding their romantic partners.
      Individuals who held more anxious or avoidant perceptions of romantic partners
      displayed more problematic conflict tactics if they possessed insecure GAR;
      however, these associations were dependent on the type of conflict behavior and
      the type of insecure GAR. Implications for future research are discussed.

PMID- 16000266
TI  - It's a bet! A problem-solving approach promotes the construction of contingent
      agreements.
AB  - Negotiators often have different expectations about the future. A contingent
      agreement, or a bet that makes the ultimate outcome dependent on some future
      event, builds on negotiators' differences. The authors argue that a problem
      solving approach, in which negotiators thoroughly explore options to build on
      their differences, is most likely to construct contingent agreements. The authors
      explore two factors expected to influence this problem-solving approach, namely,
      negotiators' relational and accountability concerns. The authors argue when these
      considerations are imbalanced, negotiators are less likely to adopt a problem
      solving style and construct a contingent agreement. To test this hypothesis,
      negotiators' relationships and accountability pressures were manipulated in two
      experiments. In Experiment 1, participants engaged in an integrative negotiation,
      allowing the authors to examine whether a contingent agreement was constructed
      and joint gain. Experiment 2 sought to replicate and extend the findings of
      Experiment 1 using a scenario study. Results across the two experiments support
      the authors' hypotheses.

PMID- 16000267
TI  - The apple does not fall far from the tree: attachment styles and personality
      vulnerabilities to depression in three generations of women.
AB  - The intergenerational transmission of attachment insecurity was examined in a
      community sample of 300 participants consisting of 100 three-generation triads of
      women. It was hypothesized that personality vulnerabilities mediate the
      association between attachment insecurity and depression within each generation.
      Findings show significant intergenerational congruence of trait vulnerabilities
      and attachment styles. Moreover, the second generation's attachment dimensions
      and personality vulnerabilities were found to mediate the association between
      first- and third-generation scores on attachment and vulnerability variables.
      Findings supported the following hypothesized within- and between-generation
      paths: Within generations, self-criticism was found to mediate the association
      between attachment insecurity and depression; between generations, depression,
      but not self-criticism, mediated the association between assessments of
      attachment insecurity in mothers and their daughters. This study constitutes a
      first approach to the delineation of the role played by self-criticism in the
      association between negative models of the self and depression across
      generations.

PMID- 16000268
TI  - When subgroups secede: extending and refining the social psychological model of
      schism in groups.
AB  - This article is about a field study (N=1,080) concerning the secession of a
      subgroup from the Church of England, and it is aimed at extending and refining
      the existing social psychological model of schisms in groups. It was found that
      the first step toward a schism is the belief that the group identity has been
      subverted. This belief will prompt negative emotions (i.e., dejection and
      agitation) and decrease both group identification and perceived group
      entitativity (i.e., cohesion, oneness). In turn, low group entitativity will
      reduce the level of group identification. Finally, low group identification and
      high negative emotions will increase schismatic intentions. It is also
      demonstrated that the negative impact of group identification, and the positive
      impact of negative emotions, on schismatic intentions is moderated by the
      perceived ability to voice dissent (i.e., the greater the perceived voice, the
      weaker the impact).

PMID- 16000269
TI  - Regulatory focus at the bargaining table: promoting distributive and integrative
      success.
AB  - The authors demonstrate that in dyadic negotiations, negotiators with a promotion
      regulatory focus achieve superior outcomes than negotiators with prevention
      regulatory focus in two ways. First, a promotion focus leads negotiators to claim
      more resources at the bargaining table. In the first two studies, promotion
      focused negotiators paid more attention to their target prices(i.e., their ideal
      outcomes) and achieved more advantageous distributive outcomes than did
      prevention-focused negotiators. The second study also reveals an important
      mediating process: Negotiators with a promotion focus made more extreme opening
      offers in their favor. Second, a promotion focus leads negotiators to create more
      resources at the bargaining table that benefit both parties. A third study
      demonstrated that in a multi-issue negotiation, a promotion focus increased the
      likelihood that a dyad achieved a jointly optimal or Pareto efficient outcome
      compared to prevention-focused dyads. The discussion focuses on the role of
      regulatory focus in social interaction and introduces the notion of interaction
      fit.

PMID- 16000270
TI  - Testing the generality of the name letter effect: name initials and everyday
      attitudes.
AB  - The name letter effect is the tendency to evaluate alphabetical letters in one's
      name, especially initials, particularly favorably. Recent evidence suggests that
      name initials may even predict career choices. The authors investigated whether
      people possess favorable attitudes toward basic attitude objects beginning with
      name initials, both between individuals (e.g., does Judy like jam more than does
      Doug?) and within individuals (e.g., does Judy like jam more than honey?).
      Ratings of animals, foods, leisure activities (Studies 1-4) and national groups
      (Studies 2-4) revealed no object preference as a function of matching name
      initials. However, the name letter effect emerged (Studies 3-4), as did a clear
      preference for brand names starting with one's name initials (Study 4). Self
      esteem, narcissism, and stimuli characteristics did not reliably influence these
      effects. Implications for extending name letter effects to basic attitude
      processes are discussed.

PMID- 16000271
TI  - Beliefs about power and its relation to emotional experience: a comparison of
      Japan, France, Germany, and the United States.
AB  - This research examined the concept of power in Japan, France, Germany, and the
      United States, as well as beliefs about the emotions persons in power tend to
      elicit in others and about powerful people's regulation (specifically,
      inhibition) of certain emotions. Definitions of power were assessed by examining
      the importance of two main components: control over self versus other and freedom
      of action vis-a-vis social norms. Beliefs about both positive (pride, admiration)
      and negative (jealousy, contempt) emotions were measured. Analyses revealed that
      the concept of power differed across countries and that the definitions of power
      as well as country of origin significantly predicted beliefs about the emotions
      that are elicited in others by powerful people and also the regulation of
      expression of emotion by powerful people.

PMID- 16000272
TI  - Two distinct emotional experiences in romantic relationships: effects of
      perceptions regarding approach of intimacy and avoidance of conflict.
AB  - This study examined how perceived position and velocity regarding approach and
      avoidance in romantic relationships relate to affective experiences. The authors
      hypothesized that perceived progress toward intimacy would predict positive
      affect and that perceived movement toward conflict would predict anxious affect.
      Ninety-two romantic couples recorded perceived levels of, and perceived changes
      in, both intimacy and conflict twice daily throughout 10 consecutive days using
      electronic palm-top devices. Multilevel modeling demonstrated that perceived
      increase in intimacy related to positive affect above and beyond perceptions of
      intimacy, conflict, and changes in conflict, for both male and female partners.
      Perceived increase in conflict related to anxious affect above and beyond
      perceptions of conflict, intimacy, and changes in intimacy, but only among male
      partners. Findings support a dual-process view of these feelings in romantic
      relationships and suggest that increases in positive feelings in close
      relationships depend on enhancing intimacy rather than on decreasing conflict.

PMID- 16000273
TI  - Happiness as a belief system: individual differences and priming in emotion
      judgments.
AB  - Three studies involving 104 undergraduates sought to examine how an individual's
      level of life satisfaction organizes their knowledge concerning the self's
      emotions. Participants judged the self's positive and negative emotions within a
      computerized task. Key results sought to determine whether judging two positive
      emotions in a consecutive sequence speeds the second judgment--a pattern of
      priming that would suggest a tighter, more interconnected structure in semantic
      memory related to one's positive emotions. As expected, individual differences in
      life satisfaction predicted the magnitude of this priming effect (Studies 1 & 2),
      which appeared to be unique to judgments of the self's emotions (Study 3). The
      results indicate that happy, relative to less happy, individuals organize
      information concerning their positive emotions in a qualitatively different and
      tighter semantic manner.

PMID- 16000274
TI  - Differential relationships between intergroup contact and affective and cognitive
      dimensions of prejudice.
AB  - Research on affective dimensions of intergroup relationships suggests that
      positive effects of intergroup contact can generalize through establishing
      affective ties with outgroup members. However, research on cognitive dimensions
      emphasizes that it is often difficult to generalize positive contact outcomes. In
      this research, the authors examine whether affective and cognitive dimensions of
      prejudice bear different relationships to intergroup contact. Using data from a
      larger meta-analysis of contact effects, Study 1 demonstrates that affective
      indicators of prejudice typically yield stronger, inverse contact-prejudice
      relationships than such cognitive indicators as stereotypes. Study 2 replicates
      these trends in a survey study using multiple indicators of affective and
      cognitive dimensions of prejudice. Study 2 also shows significant, inverse
      relationships between contact and affective prejudice when contact is assessed
      either as number of outgroup friends or intergroup closeness. Together, these
      results suggest that affective dimensions of intergroup relationships are
      especially critical for understanding the nature of contact-prejudice effects.

PMID- 16000275
TI  - Empirically treating high serum thyroglobulin levels.

PMID- 16000276
TI  - Sympathetic denervation and reinnervation after the maze procedure.
AB  - We evaluated serial changes in cardiac sympathetic nerve distribution using 123I
      metaiodobenzylguanidine (123I-MIBG) after the Maze procedure. The Maze procedure,
      in which multiple incisions are made in the atrium, has been concomitantly
      performed with mitral valve (MV) surgery in an attempt to eliminate atrial
      fibrillation (AF). Although attenuation of the sinoatrial node response to
      exercise and a reduction of left ventricular function (left ventricular ejection
      fraction [LVEF]) in early stages after the Maze procedure have been suggested,
      factors leading to these changes have not been clarified. METHODS: Thirteen
      patients with MV disease were enrolled in this study. Six of them had undergone
      MV surgery and the Maze procedure (Maze+), and 7 had undergone MV surgery without
      the Maze procedure (Maze-). All patients underwent cardiac 123I-MIBG imaging
      preoperatively and 10 d and 1 y after surgery to assess 123I-MIBG uptake (heart
      to-mediastinum count ratio of early planar images [H/M]) and the washout rate
      (WR). Radionuclide ventriculography was also performed to calculate LVEF 3 d
      after each 123I-MIBG imaging. RESULTS: The LVEF of the Maze+ group significantly
      decreased 10 d after surgery (44.2 +/- 4.8; mean +/- SD) compared with that
      before surgery (60.3 +/- 6.9; P < 0.05) and significantly increased at 1 y (65.2
      +/- 2.9) compared with that at 10 d (P < 0.05). In the Maze- group, there was no
      significant change 10 d (53.0 +/- 12.3) and 1 y (58.6 +/- 4.8) after surgery
      compared with that before surgery (60.4 +/- 4.6) (P = not significant, each). In
      the Maze+ group, the H/M (1.51 +/- 0.18) was significantly lower at 10 d after
      than that at the preoperative stage (1.90 +/- 0.25; P < 0.05) but significantly
      recovered at 1 y (2.23 +/- 0.18; P < 0.05) with a similar transient increase in
      the WR (36.7% +/- 6.1% at preoperative stage; 46.9% +/- 3.4% at 10 d; 39.9% +/-
      6.5% at 1 y; P < 0.05, each). On the other hand, the Maze- group did not show a
      significant change in the H/M (1.94 +/- 0.32, 2.06 +/- 0.18, and 2.13 +/- 0.17,
      respectively; P = not significant, each) but did exhibit a significant decrease
      in the WR (40.4% +/- 5.1%, 37.0% +/- 5.1%, and 32.9% +/- 2.5%, respectively; P <
      0.05, each). Changes in the H/M of both groups significantly correlated with the
      change in LVEF (r = 0.82; P < 0.05), and the WR showed a significant inverse
      correlation with changes in the LVEF (r = -0.81; P < 0.05). CONCLUSION: Cardiac
      sympathetic nerves were denervated at early stage and reinnervated at late stage
      after the Maze procedure. Such adrenergic nerve changes may be correlated, at
      least in part, with changes in left ventricular function after this procedure.

PMID- 16000277
TI  - Prognostic significance of dipyridamole-induced ST depression in patients with
      normal 82Rb PET myocardial perfusion imaging.
AB  - Recent studies have shown that vasodilator-induced ischemic electrocardiographic
      (ECG) changes have incremental prognostic value over normal SPECT myocardial
      perfusion imaging (MPI) and identify patients at higher risk for cardiac events.
      The prognostic value of vasodilator-induced ischemic ECG changes in the setting
      of normal PET MPI has yet to be determined. We sought to determine the prognostic
      importance of dipyridamole-induced ischemic ECG changes in patients with normal
      82Rb PET myocardial perfusion images. METHODS: Between 2000 and 2003, 2,029
      consecutive patients undergoing dipyridamole stress 82Rb PET at the University of
      Ottawa Heart Institute were evaluated. Patients with normal PET MPI and
      interpretable ECGs were enrolled. Electrocardiograms were assessed for ST
      depression or elevation and patients were categorized into those with and without
      dipyridamole-induced ischemic ECG changes. Images were graded using the 17
      segment model. Follow-up information was obtained by telephone interview, from
      hospital records, or from treating physicians. All cardiac events (cardiac death,
      nonfatal myocardial infarction [MI], percutaneous coronary intervention, coronary
      artery bypass grafting, or angiography) were verified with hospital records.
      RESULTS: Of the 629 enrolled patients with normal PET MPI, 72 patients had
      dipyridamole-induced ischemic ECG changes. There was no significant difference
      between the 2 groups in the combined endpoint (cardiac death, nonfatal MI, and
      revascularization) at follow-up (mean +/- SD, 27.1 +/- 13 mo). There were no
      cardiac deaths in either group. One (1.4%) patient with ischemic ECG changes had
      a nonfatal MI (0.6% annual event rate). Two (2.8%) patients with ischemic ECG
      changes required revascularization compared with 11 (2.0%) in the nonischemic ECG
      group. CONCLUSION: Normal 82Rb PET confers an excellent prognosis regardless of
      dipyridamole-induced ST depression.

PMID- 16000278
TI  - Assessment of diastolic function using 16-frame 99mTc-sestamibi gated myocardial
      perfusion SPECT: normal values.
AB  - The purposes of this study were (a) to assess the feasibility of diastolic
      function (DFx) evaluation using standard 16-frame postexercise gated (99m)Tc
      sestamibi myocardial perfusion SPECT (MPS), (b) to determine the relationship of
      the 2 common DFx parameters, peak filling rate (PFR) and time to peak filling
      (TTPF), to clinical and systolic function (SFx) variables in patients with normal
      myocardial perfusion and SFx, and (c) to derive and validate normal limits.
      METHODS: Ninety patients (71 men; age, 30-79 y) with normal exercise gated MPS
      were studied. None had hypertension, diabetes, rest electrocardiogram
      abnormality, or known cardiac disease. All patients reached > or = 85% of maximum
      predicted heart rate (HR). The population was randomized into derivation (n = 50)
      and validation (n = 40) groups. Univariable and multivariable approaches were
      deployed to assess the influence of clinical and functional variables on DFx
      parameters. RESULTS: PFR and TTPF were assessed in all patients. Mean values of
      PFR and TTPF in the whole study population were 2.62 +/- 0.46 end-diastolic
      volumes per second (EDV/s) and 164.6 +/- 21.7 ms, respectively. By applying a 2
      SD cutoff to the mean values in the derivation group, the threshold for abnormal
      PFR and the threshold for abnormal TTPF were < 1.71 EDV/s and > 216.7 ms,
      respectively. The normalcy rates in the validation group for PFR and TTPF were
      both 100%. The PFR showed weak but significant correlations with age, EDV, end
      systolic volume, left ventricular ejection fraction (LVEF), and poststress HR.
      However, TTPF did not correlate with these parameters. Final normal thresholds
      determined from the combined populations were PFR = 1.70 EDV/s and TTPF = 208 ms.
      Multivariable analysis showed that age, sex, LVEF, and HR are strong predictors
      for PFR, whereas TTPF was not influenced by any clinical or SFx variable.
      CONCLUSION: With a new algorithm in QGS, assessment of LV DFx is feasible using
      16-frame gated MPS even without bad-beat rejection, resulting in normal limits
      similar to those reported with gated blood-pool studies. However, due to the
      dependency of PFR on SFx parameters, sex, HR, and age, TTPF appears to be a
      stable and more useful parameter with this approach. The clinical usefulness of
      these findings requires further study.

PMID- 16000279
TI  - Clinical testing of an optimized software solution for an automated, observer
      independent evaluation of dopamine transporter SPECT studies.
AB  - A lack of standardized evaluation procedures for dopamine transporter (DAT) SPECT
      investigations impairs both intra- and interindividual comparisons as well as
      multicenter trials-for example, for assessment of disease progression or the
      response to various drug treatments. Therefore, the aim of this study was to
      evaluate a novel automated method, which has been specifically developed for a
      standardized quantification of N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4
      iodophenyl)nortropane (123I-FP-CIT) SPECT studies. METHODS: DAT binding ratios of
      155 (123)I-FP-CIT SPECT studies in 14 control subjects and 141 patients referred
      to confirm or exclude a presynaptic dopaminergic deficit were determined manually
      and by a fully automated technique. The latter included coregistration of patient
      studies to an 123I-FP-CIT mean template of controls with specialized, nonrigid
      adjustment for variation in striatal location, followed by calculation of
      specific striatal DAT binding using a standardized 3-dimensional volume-of
      interest (VOI) map. The map is based on a MR scan and covers the striatum (S),
      caudate (C), putamen (P), and an occipital reference region. The semiquantitative
      ratios of both methods were compared with the visual findings. RESULTS: Excellent
      linear correlations were observed between manually and automatically determined
      results (S: r = 0.99; C: r = 0.99; P: r = 0.99; P < 0.001, respectively).
      Automated evaluations delivered highly reproducible and visually exact
      coregistrations. Individual variations in striatal anatomy (e.g., atrophy) were
      considered and VOI positions were corrected before quantification. Both the
      manual and the automated method showed identical accuracy in supporting the
      visual diagnoses. CONCLUSION: In a large patient population, excellent agreement
      was observed between quantitative DAT results using a time-consuming, observer
      dependent, conventional manual method and the objective, automated evaluation
      specifically developed for a standardized evaluation of 123I-FP-CIT SPECT
      studies. It is suggested that the novel automated technique may substantially
      facilitate both intra- and interindividual comparisons as well as multicenter
      trials.

PMID- 16000280
TI  - Quantification of 123I-PE2I binding to dopamine transporter with SPECT after
      bolus and bolus/infusion.
AB  - The aim of the present study was to describe a method combining easy
      implementation in a clinical setting with accuracy and precision in
      quantification of 123I-labeled N-(3-iodoprop-(2E)-enyl)-2beta-carboxymethoxy
      3beta-(4'-methylphenyl)nortropane (PE2I) binding to brain dopamine transporter.
      METHODS: Five healthy subjects (mean age, 50 y; range, 40-68 y) were studied
      twice. In the first experiment, dynamic SPECT data and arterial plasma input
      curves obtained after 123I-PE2I bolus injection were assessed using Logan,
      kinetic, transient equilibrium, and peak equilibrium analyses. Accurate and
      precise determination of BP1 (binding potential times the free fraction in the
      metabolite-corrected plasma compartment) and BP2 (binding potential times the
      free fraction in the intracerebral nonspecifically bound compartment) was
      achieved using Logan analysis and kinetic analysis, with a total study time of 90
      min. In the second experiment, (123)I-PE2I was administrated as a combined bolus
      and constant infusion. The bolus was equivalent to 2.7 h of constant infusion.
      RESULTS: The bolus-to-infusion ratio of 2.7 h was based on the average terminal
      clearance rate from plasma in the bolus experiments. Steady state was attained in
      brain and plasma within 2 h, and time-activity curves remained constant for
      another 2 h. Even when an average bolus-to-infusion ratio was used, the striatal
      BP1 and BP2 values calculated with kinetic analysis (BP1 = 21.1 +/- 1.1; BP2 =
      4.1 +/- 0.4) did not significantly differ from those calculated with
      bolus/infusion analysis (BP1 = 21.0 +/- 1.2; BP2 = 4.3 +/- 0.3). Computer
      simulations confirmed that a 2-fold difference in terminal clearance rate from
      plasma translates into only a 10% difference in BP1 and BP2 calculated from 120
      to 180 min after tracer administration. CONCLUSION: The bolus/infusion approach
      allows accurate and precise quantification of 123I-PE2I binding to dopamine
      transporter and is easily implemented in a clinical setting.

PMID- 16000281
TI  - 5-HT 1A receptors are reduced in temporal lobe epilepsy after partial-volume
      correction.
AB  - Preclinical studies suggest that serotonin 1A receptors (5-HT 1A) play a role in
      temporal lobe epilepsy (TLE). Previous PET studies reported decreased 5-HT 1A
      binding ipsilateral to epileptic foci but did not correct for the partial-volume
      effect (PVE) due to structural atrophy. METHODS: We used PET with 18F-trans-4
      fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2
      pyridyl)cyclohexanecarboxamide (18F-FCWAY), a 5-HT 1A receptor antagonist, to
      study 22 patients with TLE and 10 control subjects. In patients, 18F-FDG scans
      also were performed. An automated MR-based partial-volume correction (PVC)
      algorithm was applied. Psychiatric symptoms were assessed with the Beck
      Depression Inventory Scale. RESULTS: Before PVC, significant (uncorrected P <
      0.05) reductions of 18F-FCWAY binding potential (BP) were detected in both mesial
      and lateral temporal structures, mainly ipsilateral to the seizure focus, in the
      insula, and in the raphe. Group differences were maximal in ipsilateral mesial
      temporal regions (corrected P < 0.05). After PVC, differences in mesial, but not
      lateral, temporal structures and in the insula remained highly significant
      (corrected P < 0.05). Significant (uncorrected P < 0.05) BP reductions were also
      detected in TLE patients with normal MR images (n = 6), in mesial temporal
      structures. After PVC, asymmetries in BP remained significantly greater than for
      glucose metabolism in hippocampus and parahippocampus. There was a significant
      inverse relation between the Beck Depression score and the ipsilateral
      hippocampal BP, both before and after PVC. CONCLUSION: Our study shows that in
      TLE patients, reductions of 5-HT 1A receptor binding in mesial temporal
      structures and insula are still significant after PVC. In contrast, partial
      volume effects may be an important contributor to 5-HT 1A receptor-binding
      reductions in lateral temporal lobe. Reduction of 5-HT 1A receptors in the
      ipsilateral hippocampus may contribute to depressive symptoms in TLE patients.

PMID- 16000282
TI  - 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective
      study of 124 patients with histologic correlation.
AB  - Accurate evaluation of primary tumors and cervical lymph node status of squamous
      cell carcinoma (SCC) of the oral cavity is important to treatment planning and
      prognosis prediction. In this prospective study, we evaluated the use of 18F-FDG
      PET, CT/MRI, and their visual correlation for the identification of primary
      tumors and cervical nodal metastases of SCC of the oral cavity with histologic
      correlation. METHODS: One hundred twenty-four patients with pathologically proven
      diagnoses of oral cavity SCC underwent 18F-FDG PET and CT/MRI within 2 wk before
      surgery. We interpreted 18F-FDG PET, CT/MRI, and visually correlated 18F-FDG PET
      and CT/MRI separately to assess the primary tumors and their regional lymph node
      status. We recorded lymph node metastases according to the neck level system of
      imaging-based nodal classification. Histopathologic analysis was used as the gold
      standard for assessment of the primary tumors and lymph node involvement. We
      analyzed differences in sensitivity and specificity among the imaging modalities
      using the McNemar test. The receiver-operating-characteristic (ROC) curve and
      calculation of the area under the curve were used to evaluate their
      discriminative power. RESULTS: The accuracy of 18F-FDG PET, CT/MRI, and their
      visual correlation for the identification of primary tumors was 98.4%, 87.1%, and
      99.2%, respectively. The sensitivity of 18F-FDG PET for the identification of
      nodal metastases on a level-by-level basis was 22.1% higher than that of CT/MRI
      (74.7% vs. 52.6%, P < 0.001), whereas the specificity of 18F-FDG PET was 1.5%
      lower than that of CT/MRI (93.0% vs. 94.5%, P = 0.345). The sensitivity and
      specificity of the visual correlation of 18F-FDG PET and CT/MRI were 3.2% and
      1.5% higher than those of 18F-FDG PET alone (77.9% vs. 74.7%, P = 0.25; 94.5% vs.
      93.0%, P = 0.18, respectively). The area under the curve obtained from the ROC
      curve showed that 18F-FDG PET was significantly superior to CT/MRI for total
      nodal detection (0.896 vs. 0.801, P = 0.002), whereas the visual correlation of
      18F-FDG PET and CT/MRI was modestly superior to 18F-FDG PET alone (0.913 vs.
      0.896, P = 0.28). CONCLUSION: 18F-FDG PET is superior to CT/MRI in the detection
      of cervical status of oral cavity SCC. The sensitivity of 18F-FDG PET for the
      detection of cervical nodal metastasis on a level-by-level basis was
      significantly higher than that of CT/MRI, whereas their specificities appeared to
      be similar. Visual correlation of 18F-FDG PET and CT/MRI showed a trend of
      increased diagnostic accuracy over 18F-FDG PET alone but without a statistically
      significant difference, and its sensitivity was still not high enough to replace
      pathologic lymph node staging based on neck dissection.

PMID- 16000283
TI  - Early prediction of response to chemotherapy in metastatic breast cancer using
      sequential 18F-FDG PET.
AB  - Chemotherapy is currently the treatment of choice for patients with high-risk
      metastatic breast cancer. Clinical response is determined after several cycles of
      chemotherapy by changes in tumor size as assessed by conventional imaging
      procedures including CT, MRI, plain film radiography, or ultrasound. The aim of
      this study was to evaluate the use of sequential 18F-FDG PET to predict response
      after the first and second cycles of standardized chemotherapy for metastatic
      breast cancer. METHODS: Eleven patients with 26 metastatic lesions underwent 31
      (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission
      and transmission scans). Clinical response, as assessed by conventional imaging
      after completion of chemotherapy, served as the reference. 18F-FDG PET images
      after the first and second cycles of chemotherapy were analyzed
      semiquantitatively for each metastatic lesion using standardized uptake values
      (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F
      FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of
      metastatic lesions within individual patients and compared with conventional
      imaging results after the third and sixth cycles of chemotherapy. RESULTS: After
      completion of chemotherapy, 17 metastatic lesions responded, as assessed by
      conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21%
      after the first cycle and 54% +/- 16% after the second cycle, when compared with
      the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to
      chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79%
      +/- 9% after the second cycle. The differences between responding and
      nonresponding lesions were statistically significant after the first (P = 0.02)
      and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly
      predicted the response in all patients as early as after the first cycle of
      chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders
      (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). CONCLUSION: In
      patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction
      of response to treatment after the first cycle of chemotherapy. The use of 18F
      FDG PET as a surrogate endpoint for monitoring therapy response offers improved
      patient care by individualizing treatment and avoiding ineffective chemotherapy.

PMID- 16000284
TI  - Stereotactic coregistration of 201Tl SPECT and MRI applied to brain tumor
      biopsies.
AB  - The aim of the present study was to determine the clinical feasibility of
      integration of stereotactic SPECT (sSPECT) with 201Tl in the stereotactic MRI
      (sMRI)-based planning of brain tumor biopsy. Furthermore, the predictive value of
      the integrated techniques was analyzed by comparison with the corresponding
      histologically determined metabolic activity. METHODS: Ten patients underwent
      combined 201Tl SPECT- and MRI-guided stereotactic biopsy of intracranial lesions
      according to a previously described technique. An area of abnormal 201Tl uptake
      was used to guide the stereotactic biopsy trajectory. Several samples were taken
      along the trajectory above and beneath the target. An extensive histologic
      diagnosis (tumor grade, mitotic index [MI], and Ki67 index) and the 201Tl index
      were obtained for all samples and compared statistically. RESULTS: Combined 201Tl
      sSPECT- and sMRI-guided biopsy could be performed on all patients. Ki67 index,
      MI, and tumor grade correlated significantly. The correlations between MI or Ki67
      index and 201Tl index were not significant (0.18 and 0.09, respectively). A trend
      to significance existed between tumor grade and 201Tl index (R = 0.31; P = 0.06).
      Mean 201Tl index for grade III tumors (3.27 +/- 1.89 [SD]) was significantly
      different from that for grade IV tumors (4.34 +/- 1.29). The sample position on
      the trajectory correlated with the MI (R = 0.39; P = 0.01). In 4 of the 10
      patients, a variation in tumor grade could be observed along the trajectory. In
      all patients, the highest proliferative activity was within 5-10 mm of the
      target. CONCLUSION: These results support the view that 201Tl SPECT may
      contribute to the successful management of brain tumor patients requiring
      stereotactic biopsy, without causing a significant increase in discomfort or
      morbidity. The development of similar techniques integrating sSPECT data in the
      planning of stereotactic biopsy should be considered by centers performing
      stereotactic surgery and having access to SPECT technology. In the long term,
      this technique could become a support for focused gene therapy and cell transfer.

PMID- 16000285
TI  - Detection of Klatskin's tumor in extrahepatic bile duct strictures using delayed
      18F-FDG PET/CT: preliminary results for 22 patient studies.
AB  - Detection of cholangiocarcinoma in extrahepatic bile duct strictures is a
      continuing challenge in clinical practice because brush cytology taken at
      endoscopic retrograde cholangiography has an average sensitivity of 50%. The aim
      of this study was to evaluate the effectiveness of dual-modality PET/CT using
      (18)F-FDG for noninvasive differentiation of extrahepatic bile duct strictures.
      METHODS: Twenty-two PET/CT studies were performed on 20 patients (10 women, 10
      men; mean age +/- SD, 63 +/- 14 y) with extrahepatic bile duct strictures on
      endoscopic retrograde cholangiography. PET imaging was started 101 +/- 22 min
      after injection of 369 +/- 48 MBq of 18F-FDG. Blood glucose was 100 +/- 20 mg/dL.
      PET images were reconstructed iteratively with attenuation correction based on a
      rescaling of the CT image. CT was performed within 1 min before the PET study,
      with the patient in the same position. CT was used to place a volume of interest
      5 cm in diameter at the liver hilus for quantitative evaluation of PET images by
      means of standardized uptake values (SUVs). RESULTS: Final diagnosis was
      histologically proven cholangiocarcinoma in 14 cases and benign causes of
      strictures in 8 cases without evidence of malignancy during a follow-up of 18 +/-
      3 mo. All patients with cholangiocarcinoma presented with focal increased uptake
      in the liver hilus with an SUV of 6.8 +/- 3.3 (range, 3.9-15.8), compared with
      2.9 +/- 0.3 (range, 2.5-3.3) in patients with benign causes of strictures (P =
      0.003). There was a clear cutoff SUV of 3.6 for detection of malignancy in the
      liver hilus. CONCLUSION: 18F-FDG PET/CT provided high accuracy for noninvasive
      detection of perihilar cholangiocarcinoma in extrahepatic bile duct strictures.

PMID- 16000286
TI  - Is empiric 131I therapy justified for patients with positive thyroglobulin and
      negative 131I whole-body scanning results?
AB  - The long-term monitoring of patients with differentiated thyroid carcinoma (DTC)
      is essential throughout the patient's life after total or nearly total
      thyroidectomy followed by 131I remnant ablation and thyroid hormone suppression
      of thyroid-stimulating hormone (TSH). Sensitive surveillance for DTC recurrences
      and metastases includes radioiodine diagnostic whole-body scanning (DWBS) and
      measurement of serum thyroglobulin (Tg) levels after endogenous or exogenous TSH
      stimulation. Serum Tg levels during thyroid hormone withdrawal usually are
      correlated well with the results of DWBS. In general, Tg levels undetectable by
      DWBS suggest complete remission, whereas detectable or elevated Tg concentrations
      are suggestive of the presence of 131I uptake in local or distant metastases.
      However, DTC patients with a positive Tg test and negative 131I DWBS results (Tg+
      DWBS-) have been observed in follow-up studies. The management of these cases
      begets controversy. METHODS: We electronically searched Medline (1966-2004.3),
      Embase (1984-2003), the Cochrane Library (2004, 2nd edition), CNKI (1994-2004),
      and CBM-DISC (1978-2004). We also manually searched the Chinese Journal of
      Isotopes, Radiologia pratica, and the Chinese Journal of Endocrinology and
      Metabolism. RESULTS: Ten serial observations and 3 nonrandomized controlled
      trials were found. The available data showed that of 314 patients who were
      treated empirically with 131I, 194 (62%) of 314 displayed pathologic uptake in
      the thyroid bed, lung, bone, mediastinum, and lymph nodes. In studies with Tg-on
      and Tg-off data, 171 (63%) of 271 patients achieved a decrease in Tg. CONCLUSION:
      On the basis of data from recent studies, 131I therapy should be individualized
      according to clinical characteristics. More significantly, a decrease in Tg
      levels was achieved in 63% of DTC patients with Tg+ DWBS-, suggesting that 131I
      therapy does have a therapeutic effect when the Tg level is considered an index
      of tumor burden. The 62% positive posttherapy whole-body scanning results also
      indicated that a therapeutic dose of 131I could reveal approximately one half of
      previously undiagnosed lesions in some patients. Therefore, 131I therapy may be
      justified in patients with Tg levels of > 10 microg/L and DWBS- and who are at
      high risk of any recurrence.

PMID- 16000287
TI  - Absorbed fractions for alpha-particles in tissues of trabecular bone:
      considerations of marrow cellularity within the ICRP reference male.
AB  - Alpha-particles are of current interest in radionuclide therapy due to their
      short range and high rates of energy transfer to target tissues. Published values
      of alpha-particle absorbed fraction phi in the skeletal tissues, as needed for
      patient-specific dosimetry under the MIRD schema, do not generally account for
      its variation with particle energy or skeletal site. Furthermore, variations in
      alpha-particle absorbed fraction with marrow cellularity have yet to be fully
      considered. METHODS: In this study, a 3-dimensional (3D) chord-based radiation
      transport model (or 3D-CBIST) is presented, which combines (a) chord-based
      techniques for tracking alpha-particles across bone trabeculae, endosteum, and
      marrow cavities and (b) a spatial model of the marrow tissues that explicitly
      considers the presence of marrow adipocytes. Chord-length distributions are taken
      from a 44-y male subject (ICRP [International Commission on Radiological
      Protection] Reference Male) and are identical to those used currently for
      clinical dose estimates for beta-particle emitters. RESULTS: Values of phi(active
      marrow<--active marrow) given by the 3D-CBIST model are shown to be considerably
      lower than phi = 1.0 assumed under the ICRP Publication 30 and 2003 Eckerman bone
      models. For example, values of absorbed fraction for the self-dose to active bone
      marrow in the ribs, cervical vertebra, and parietal bone are 0.81, 0.80, and 0.55
      for 6-MeV alpha-particles and are 0.74, 0.72, and 0.43 for 9-MeV alpha-particles,
      where each is evaluated at ICRP reference cellularities in the 3D-CBIST model
      (72%, 72%, and 42%, respectively, at age 25 y). CONCLUSION: Improvements in
      patient-specific dosimetry of skeletal tissues require explicit consideration of
      not only changes in target mass with variable patient marrow cellularity (i.e.,
      active marrow) but also corresponding changes in values of the absorbed fraction.
      The data given in this study provide a more-firm basis for application of the
      MIRD schema to patient-specific dosimetry for newly developing therapies using
      alpha-particle emitters.

PMID- 16000288
TI  - 99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in
      porcine coronary arteries.
AB  - We used a model of porcine coronary atherosclerosis characterized by smooth
      muscle cell apoptosis to test the hypothesis that apoptosis of cells in the
      vascular wall of coronary arteries can be detected on SPECT images using a
      technetium-labeled radiotracer that targets apoptosis. METHODS: Eleven juvenile
      male swine received a high-fat diet combined with injury to 22 coronary vessels.
      After 51 +/- 9 d (mean +/- SD), the animals underwent coronary angiography, were
      injected with 403.3 +/- 48.1 MBq of 99mTc-annexin V, underwent SPECT, and were
      sacrificed. The coronary arteries underwent autoradiography and well counting,
      and immunostaining was performed for alpha-actin, caspase, and macrophages.
      RESULTS: Atherosclerotic lesions were predominantly of American Heart Association
      class II. Thirteen of the 22 injured vessels showed focal uptake of 99mTc-annexin
      V in vivo (scan positive), and 9 injured vessels and all control vessels showed
      no focal uptake (scan negative). The count ratios of the injured vessels to the
      control vessels were 2.38 +/- 0.61 for scan-positive vessels and 1.27 +/- 0.23
      for scan-negative vessels (P < 0.001). The percentages of injected dose for the
      scan-positive and scan-negative vessels were 1.73 +/- 0.83 x 10(-3) and 0.68 +/-
      0.20 x 10(-3), respectively (P < 0.001). Immunohistopathologic examination found
      that the cells undergoing apoptosis were smooth muscle cells. The apoptotic index
      (caspase-positive cells to total cells) was 63% +/- 7% for scan-positive vessels
      and 16% +/- 10% for scan-negative vessels (P < 0.001). Both the count ratio of
      injured vessels to control vessels and the percentage injected dose correlated
      significantly with death rate by regression analysis. CONCLUSION: Annexin is a
      noninvasive method to identify plaque apoptosis in the coronary vessels.

PMID- 16000289
TI  - U-SPECT-I: a novel system for submillimeter-resolution tomography with
      radiolabeled molecules in mice.
AB  - A major advance in biomedical science and diagnosis was accomplished with the
      development of in vivo techniques to image radiolabeled molecules, but limited
      spatial resolution has slowed down applications to small experimental animals.
      Here, we present a SPECT system (U-SPECT-I) dedicated to radionuclide imaging of
      murine organs at a submillimeter resolution. METHODS: The high performance of U
      SPECT-I is based on a static triangular detector setup, with a cylindric imaging
      cavity in the center and 75 gold micropinhole apertures in the cavity wall. The
      pinholes are focused on a small volume of interest such as the mouse heart or
      spine to maximize the detection yield of gamma-photons. Three-dimensional
      molecular distributions are iteratively estimated using the detector data and a
      statistical reconstruction algorithm that takes into account system blurring and
      data noise to increase resolution and reduce image noise. RESULTS: With 0.6-mm
      diameter pinholes, the maximum fraction of detected photons emitted by a point
      source (peak sensitivity) is 0.22% for a 15%-wide energy window and remains
      higher than 0.12% in the central 12 mm of the central plane. In a resolution
      phantom, radioactively filled capillaries as small as 0.5 mm and separated by 0.5
      mm can be distinguished clearly in reconstructions. Projection data needed for
      the reconstruction of cross sections of molecular distributions in mouse organs
      can readily be obtained without the need for any mechanical movements. Images of
      a mouse spine show 99mTc-hydroxymethylene diphosphonate uptake down to the level
      of tiny parts of vertebral processes. These are separated clearly from the
      vertebral and intervertebral foramina. Using another tracer, one can monitor
      myocardial perfusion in the left and right ventricular walls, even in structures
      as small as the papillary muscles. CONCLUSION: U-SPECT-I allows discrimination
      between molecular concentrations in adjacent volumes of as small as about 0.1
      muL, which is significantly smaller than can be imaged by any existing SPECT or
      PET system. Our initial in vivo images of the mouse heart and spine show that U
      SPECT-I can be used for novel applications in the study of dynamic biologic
      systems with a clear projection to clinical applications. The combination of high
      resolution and detection efficiency of U-SPECT-I opens up new possibilities for
      the suborgan-level study of radiotracers in mouse models.

PMID- 16000290
TI  - Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a
      tetravalent single-chain Fv-streptavidin fusion protein.
AB  - Mesothelin is a glycoprotein that is overexpressed in several human tumors,
      including mesotheliomas and ovarian cancers, and has been identified as a
      potential target for therapy. We evaluated the biodistribution and tumor
      targeting ability of an antimesothelin tetravalent single-chain Fv-streptavidin
      fusion protein (SS1scFvSA) in mice. METHODS: SS1scFvSA was labeled with 125I or
      111In for evaluation of internalization in vitro and for optimization of its
      biodistribution. The A431-K5 mesothelin transfected cell line was used as the
      target. We used a 3-step pretargeting approach consisting of injections of (i)
      SS1scFvSA, followed 20 h later by (ii) a synthetic clearing agent, and (iii) 4 h
      later, radiolabeled (111In, 88Y/90Y, or 177Lu) 1,4,7,10-tetraazacyclododecane
      N,N',N'',N'''-tetraacetic acid (DOTA)-biotin. To optimize the tumor uptake, the
      effect of the specific activity of 111In-DOTA-biotin was evaluated. RESULTS:
      Approximately 60% of SS1sc FvSA internalized within 6 h. The optimal dose of
      SS1scFvSA for pretargeting was 600 microg. Decreasing the specific activity of
      DOTA-biotin by administering 0.1-5 microg of DOTA-biotin resulted in tumor uptake
      decreasing from 31.8 to 5.5 %ID/g (percentage injected dose per gram) at 2 h.
      Pretargeted therapy of A431-K5 tumor with 90Y doses of 11.1-32.4 MBq resulted in
      a dose-dependent tumor response. With 32.4 MBq, 86% of mice survived tumor free
      for 110 d. All nontreated mice died, with a median survival of 16 d. CONCLUSION:
      SS1scFvSA localized in the mesothelin-expressing tumor, resulting in a high
      accumulation of radiolabeled DOTA-biotin. The specific activity of DOTA-biotin
      had a significant effect on its tumor uptake. Therapeutic tumor doses were
      obtained without dose-limiting toxicity.

PMID- 16000291
TI  - 64Cu-labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging
      and radiotherapy: synthesis, radiolabeling, and biologic evaluation.
AB  - Long-circulating nanoparticles functionalized with ligands for receptors
      overexpressed by tumor cells have promising applications for active and passive
      tumor targeting. The purpose of this study was to evaluate 64Cu-radiolabeled
      folate-conjugated shell cross-linked nanoparticles (SCKs) as candidate agents to
      shuttle radionuclides and drugs into tumors overexpressing the folate receptor
      (FR). METHODS: SCKs were obtained by cross-linking the shell of micelles obtained
      from amphiphilic diblock copolymers. SCKs were then functionalized with folate,
      fluorescein thiosemicarbazide (FTSC), and 1,4,8,11-tetraazacyclotetradecane
      N,N',N'',N'''-tetraacetic acid (TETA). The specific interaction of SCK-folate
      with the FR was investigated on KB cells. The biodistributions of 64Cu-TETA-SCK
      and 64Cu-TETA-SCK-folate were evaluated in athymic mice bearing small-size KB
      cell xenografts (10-100 mg), whereas the intratumor distributions were
      investigated by autoradiography in 0.3- to 0.6-g KB cell xenografts. RESULTS: A
      global solution-state functionalization strategy has been introduced for
      attaching optimum numbers of targeting and imaging agents onto the SCKs for
      increasing the efficiency of interaction with cell-surface receptors.
      Epifluorescence microscopy confirmed the specific interaction of FTSC-SCK-folate
      with the FR in vitro. 64Cu labeling of TETA-SCKs led to the radiolabeled
      compounds with 15%-20% yield and >95% radiochemical purity. The biodistribution
      results demonstrated high accumulation of 64Cu-labeled SCKs in organs of the
      reticuloendothelial system (RES) (56.0 +/- 7.1 %ID/g and 45.7 +/- 3.5 %ID/g
      [percentage injected dose per gram] in liver at 10 min after injection for
      folated and nonfolated SCKs, respectively) and a prolonged blood circulation. No
      increase of SCK tumor uptake deriving from folate conjugation was observed (5.9
      +/- 2.8 %ID/g and 6.0 +/- 1.9 %ID/g at 4 h after injection for folated and
      nonfolated SCKs, respectively). However, tumor accumulation was higher in small
      size tumors, where competitive block of SCK-folate uptake with excess folate was
      observed. Autoradiography results confirmed the extravasation of radiolabeled
      SCKs in vascularized areas of the tumor, whereas no diffusion was observed in
      necrotic regions. CONCLUSION: Despite high RES uptake, the evaluated 64Cu-labeled
      SCKs exhibited long circulation in blood and were able to passively accumulate in
      tumors. Furthermore, SCK-folate uptake was competitively blocked by excess folate
      in small-size solid tumors, suggesting interaction with the FR. For these
      reasons, functionalized SCKs are promising drug-delivery agents for imaging and
      therapy of early-stage solid tumors.

PMID- 16000292
TI  - Parametric imaging of myocardial blood flow with 15O-water and PET using the
      basis function method.
AB  - Regional myocardial blood flow (MBF) can be measured with 15O-water and PET using
      the 1-tissue-compartment model with perfusable tissue fraction, which provides an
      MBF value that is free from the partial-volume effect. Studies with 15O-water
      have several advantages, such as the ability to repeat a scan. However, because
      of the short scanning time and the small distribution volume of 15O-water in the
      myocardium, the image quality of 15O-water is limited, impeding the computation
      of MBF and perfusable tissue fraction at the voxel level. We implemented the
      basis function method for generating parametric images of MBF, perfusable tissue
      fraction, and arterial blood volume (Va) with 15O-water and PET. The basis
      function method linearizes the solution of the 1-tissue-compartment model, which
      results in a computationally much faster method than the conventional nonlinear
      least-squares fitting method in estimating the parameters. METHODS: To validate
      the basis function method, we performed a series of PET studies on miniature pigs
      (n = 7). After acquisition of the transmission scan for attenuation correction
      and the 15O-CO scan for obtaining the blood-pool image, repeated PET scans with
      15O-water were obtained with varying doses of adenosine or CGS-21680 (selective
      adenosine A(2a) receptor agonist). MBF, perfusable tissue fraction, and Va values
      of the myocardial region for each scan were computed using the basis function
      method and the nonlinear least-squares method, and the parameters estimated by
      the 2 methods were compared. RESULTS: MBF images generated by the basis function
      method demonstrated an increase in blood flow after administration of adenosine
      or CGS-21680. The MBF values estimated by the basis function method and by the
      nonlinear least-squares method correlated strongly. CONCLUSION: The basis
      function method produces parametric images of MBF, perfusable tissue fraction,
      and Va with 15O-water and PET. These images will be useful in detecting regional
      myocardial perfusion abnormalities.

PMID- 16000293
TI  - Concurrent PET/CT with an integrated imaging system: intersociety dialogue from
      the joint working group of the American College of Radiology, the Society of
      Nuclear Medicine, and the Society of Computed Body Tomography and Magnetic
      Resonance.
AB  - Rapid advances in imaging technology are a challenge for health care
      professionals, who must determine how best to use these technologies to optimize
      patient care and outcomes. Hybrid imaging instrumentation, combining 2 or more
      new or existing technologies, each with its own separate history of clinical
      evolution, such as PET and CT, may be especially challenging. CT and PET provide
      complementary anatomic information and molecular information, respectively, with
      PET giving specificity to anatomic findings and CT offering precise localization
      of metabolic activity. Historically, the acquisition and interpretation of the 2
      image sets have been performed separately and very often at different times and
      locales. Recently, integrated PET/CT systems have become available; these systems
      provide PET and CT images that are acquired nearly simultaneously and are capable
      of producing superimposed, coregistered images, greatly facilitating
      interpretation. As the implementation of this integrated technology has become
      more widespread in the setting of oncologic imaging, questions and concerns
      regarding equipment specifications, image acquisition protocols, supervision,
      interpretation, professional qualifications, and safety have arisen. This article
      summarizes the discussions and observations surrounding these issues by a
      collaborative working group consisting of representatives from the American
      College of Radiology, the Society of Nuclear Medicine, and the Society of
      Computed Body Tomography and Magnetic Resonance.

PMID- 16000294
TI  - Carcinoid crisis after injection of 6-18F-fluorodihydroxyphenylalanine in a
      patient with metastatic carcinoid.
AB  - A carcinoid crisis is a severe complication of the carcinoid syndrome that can
      arise in patients with advanced metastatic neuroendocrine tumors. It can be
      initiated by stress, catecholamines, and tumor manipulation. In this article, we
      report a case in which an injection with the catecholamine tracer 6-18F
      fluorodihydroxyphenylalanine, used for PET, induced a carcinoid crisis.
      Octreotide can be used for treatment and should be available. Tracer injection
      should be slow.

PMID- 16000295
TI  - Similitude of brain perfusion pattern in hypothyroidism and early Alzheimer's
      disease: physiopathologic considerations.

PMID- 16000296
TI  - DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity
      for H- and N-Ras.
AB  - Covalent lipid modifications mediate the membrane attachment and biological
      activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl
      methylated at the terminal cysteine; H-Ras and N-Ras are further modified by
      palmitoylation. Yeast Ras is palmitoylated by the DHHC cysteine-rich domain
      containing protein Erf2 in a complex with Erf4. Here we report that H- and N-Ras
      are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9
      and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC
      cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein that has
      limited sequence similarity to yeast Erf4. DHHC9 and GCP16 co-distribute in the
      Golgi apparatus, a location consistent with the site of mammalian Ras
      palmitoylation in vivo. Like yeast Erf2.Erf4, DHHC9 and GCP16 form a protein
      complex, and DHHC9 requires GCP16 for protein fatty acyltransferase activity and
      protein stability. Purified DHHC9.GCP16 exhibits substrate specificity,
      palmitoylating H- and N-Ras but not myristoylated G (alphai1) or GAP-43, proteins
      with N-terminal palmitoylation motifs. Hence, DHHC9.GCP16 displays the properties
      of a functional human ortholog of the yeast Ras palmitoyltransferase.

PMID- 16000297
TI  - Apoplastic calmodulin receptor-like binding proteins in suspension-cultured cells
      of Arabidopsis thaliana.
AB  - Calmodulin, a highly conserved protein family that has long been well known as an
      intracellular calcium sensor, was identified in the culture medium and cell walls
      of Arabidopsis thaliana suspension-cultured cells by immunoblotting assay. A
      promotion effect by applying exogenous purified calmodulin and an inhibition
      effect by the addition of anti-calmodulin anti-serum or calmodulin antagonist to
      the medium on proliferation of suspension cells were found by monitoring
      incorporation of [methyl-3H]thymidine into nuclear DNA. Radioligand binding
      analysis with 35S-labeled calmodulin indicated the presence of specific,
      reversible, and saturable calmodulin binding sites on the surface of both A.
      thaliana suspension-cultured cells and its protoplasts; among them at least one
      is on the surface of Arabidopsis protoplasts, with the Kd approximately 9.2 nM,
      and two are on the out-surface of Arabidopsis suspension-cultured cells, with Kd
      values of approximately 47.5 and 830 nM. Chemical crosslinking of 35S-labeled
      calmodulin to protoplasts revealed 117- and 41-kDa plasma membrane proteins
      specifically bound to calmodulin, whereas cross-linking with intact suspension
      cultured cells verified more calmodulin binding proteins which might be cell wall
      associated in addition to membrane-localized. Taking together, our data provide
      first evidence for the presence of apoplastic calmodulin receptor-like binding
      proteins on the cell surface of Arabidopsis suspension-cultured cells, which
      strongly supports our previous idea that apoplastic calmodulin functions as a
      peptide signal involved in regulation of cell growth and development.

PMID- 16000298
TI  - Radiation-induced epidermal growth factor receptor nuclear import is linked to
      activation of DNA-dependent protein kinase.
AB  - Ionizing radiation, but not stimulation with epidermal growth factor (EGF),
      triggers EGF receptor (EGFR) import into the nucleus in a probably karyopherin
      alpha-linked manner. An increase in nuclear EGFR is also observed after treatment
      with H2O2, heat, or cisplatin. During, this process, the proteins Ku70/80 and the
      protein phosphatase 1 are transported into the nucleus. As a consequence, an
      increase in the nuclear kinase activity of DNA-dependent kinase (DNA-PK) and
      increased formation of the DNA end-binding protein complexes containing DNA-PK,
      essential for repair of DNA-strand breaks, occurred. Blockade of EGFR import by
      the anti-EGFR monoclonal antibody C225 abolished EGFR import into the nucleus and
      radiation-induced activation of DNA-PK, inhibited DNA repair, and increased
      radiosensitivity of treated cells. Our data implicate a novel function of the
      EGFR during DNA repair processes.

PMID- 16000299
TI  - Free energy contributions to direct readout of a DNA sequence.
AB  - The energetic contributions of individual DNA-contacting side chains to specific
      DNA recognition in the human papillomavirus 16 E2C-DNA complex is small (less
      than 1.0 kcal mol(-1)), independent of the physical and chemical nature of the
      interaction, and is strictly additive. The sum of the individual contributions
      differs 1.0 kcal mol(-1) from the binding energy of the wild-type protein. This
      difference corresponds to the contribution from the deformability of the DNA,
      known as "indirect readout." Thus, we can dissect the energetic contribution to
      DNA binding into 90% direct and 10% indirect readout components. The lack of high
      energy interactions indicates the absence of "hot spots," such as those found in
      protein-protein interfaces. These results are compatible with a highly dynamic
      and "wet" protein-DNA interface, yet highly specific and tight, where individual
      interactions are constantly being formed and broken.

PMID- 16000300
TI  - Consequences of disease-causing mutations on lubricin protein synthesis,
      secretion, and post-translational processing.
AB  - Lubricin, a protein product of the gene PRG4, is a secreted mucin-like
      proteoglycan that is a major lubricant in articulating joints. Mutations in PRG4
      cause the autosomal recessive, human disorder camptodactyly-arthropathy-coxa vara
      pericarditis syndrome. We developed rabbit polyclonal antibodies against human
      lubricin to determine the consequence of disease-causing mutations at the protein
      level and to study the protein's normal post-translational processing. Antiserum
      generated against an epitope in the amino-terminal portion of lubricin detected
      protein in wild-type synovial fluid and in conditioned media from wild-type
      cultured synoviocytes. However, the antiserum did not detect lubricin in synovial
      fluid or cultured synoviocytes from several patients with frameshift or nonsense
      mutations in PRG4. Antiserum generated against an epitope in the protein's
      carboxyl-terminal, hemopexin-like domain identified a post-translational cleavage
      event in wild-type lubricin, mediated by a subtilisin-like proprotein convertase
      (SPC). Interestingly, in contrast to wild-type lubricin, one disease-causing
      mutation that removes the last 8 amino acids of the protein, including a
      conserved cysteine residue, was not cleaved within the hemopexin-like domain when
      expressed in COS-7 cells. This suggests that formation of an intrachain disulfide
      bond is required for SPC-mediated cleavage and that SPC-mediated cleavage is
      essential to protein function.

PMID- 16000301
TI  - Kinetic analysis of steps in the repair of damaged DNA by human O6-alkylguanine
      DNA alkyltransferase.
AB  - Rates of individual steps in the removal of alkyl groups from O6-methyl (Me) and 
      benzyl (Bz) guanine in oligonucleotides by human O6-alkylguanine DNA
      alkyltransferase (AGT) were estimated using rapid reaction kinetic methods. The
      overall reaction yields hyperbolic plots of rate versus AGT concentration for O6
      MeG but linear plots for the O6-BzG reaction, which is approximately 100-fold
      faster. The binding of AGT and DNA (double-stranded 30-mer/36-mer complex)
      appears to be diffusion-limited. The rate of dissociation of the complex is
      approximately 25-fold slower (approximately 1 s(-1)) for DNA containing O6-MeG or
      O6-BzG than unmodified DNA. The fluorescent dC-analog 6-methylpyrrolo[2,3
      d]pyrimidine-2(3H) one deoxyribonucleoside (pyrrolo dC), which pairs with G, was
      positioned opposite G, O6-MeG, or O6-BzG and used as a probe of the rate of base
      flipping. A rapid increase of fluorescence (k approximately 200 s(-1)) was
      observed with O6-MeG and O6-BzG and AGT but not with a Gly mutation at Arg128,
      which has been implicated in base flipping with crystal structures. Only weak and
      slower fluorescence changes were observed with G:pyrrolo dC or T:2-aminopurine
      pairs. These rate estimates were used in a kinetic model in which AGT binds and
      scans DNA rapidly, flips O6-alkylG residues, transfers the alkyl group in a
      chemical step that is rate-limiting in the case of O6-MeG but not O6-BzG, and
      releases the dealkylated DNA. The results explain the overall patterns of rates
      of alkyl group removal versus AGT concentration and the effects of the mutations,
      as well as the greater affinity of AGT for DNA with O6-alkylG lesions.

PMID- 16000302
TI  - Cooperative interactions between RUNX2 and homeodomain protein-binding sites are
      critical for the osteoblast-specific expression of the bone sialoprotein gene.
AB  - The bone sialoprotein (Bsp) gene provides an excellent model for studying
      mechanisms controlling osteoblast-specific gene expression. Although the RUNX2
      transcription factor directly regulates many osteoblast-related genes, its
      function in Bsp expression remains uncertain. By using chromatin
      immunoprecipitation (ChIP) analysis in MC3T3-E1 (clone MC-4) preosteoblast cells,
      RUNX2 was shown to bind a chromatin fragment containing the proximal Bsp
      promoter. Two putative RUNX2-binding sites (R1 and R2) were identified within
      this region of the mouse, rat, and human genes and were shown to bind RUNX2 in
      vitro and in vivo (by ChIP assay). Site-specific mutagenesis established that
      both sites act as osteoblast-specific transcriptional enhancers and together
      account for nearly two-thirds of the total promoter activity. In addition,
      functional cooperativity was observed between the R2 site and an adjacent
      homeodomain protein-binding site previously characterized by this laboratory (the
      C site). All three sites (R1, R2, and C) are necessary for maximal promoter
      activity in osteoblasts. DLX5 in MC-4 cell nuclear extracts binds to the C site
      in vitro. Furthermore, ChIP assays revealed that DLX5 is selectively associated
      with chromatin in the vicinity of the C site only when Bsp is transcriptionally
      active. Finally, co-immunoprecipitation assays detected a physical complex
      containing DLX5 and RUNX2. Taken together, our data show that RUNX2 is a direct
      regulator of Bsp in osteoblasts and that it functions in cooperation with DLX5 or
      a related factor to activate osteoblast-specific gene expression.

PMID- 16000303
TI  - BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human
      mesenchymal stem cells via the MAPK and protein kinase D signaling pathways.
AB  - Genetic studies place the transcription factor Osterix (Osx) downstream of Runx2,
      but limited information is available about Osx regulation during osteoblastic
      differentiation. An important role for bone morphogenetic protein-2 (BMP-2) and
      insulin-like growth factor-I (IGF-I) on Osx expression and the requirement for
      p38 for the BMP-2-mediated effect was reported previously by our group. In this
      study, we continued to investigate the molecular mechanisms by which BMP-2 and
      IGF-1 regulate Osx expression during osteoblast lineage progression. IGF-I
      mediated Osx expression required all three MAPK components (Erk, p38, and JNK),
      whereas BMP-2 required p38 and JNK signaling. As a common mediator of growth
      factor signaling, we also investigated the involvement of protein kinase C/D
      (PKC/D) signaling. BMP-2- and IGF-I-mediated Osx expression was blocked in
      response to a PKD inhibitor. A selective inhibitor of conventional PKCs had no
      effect on the BMP-2-mediated Osx expression. BMP-2 and IGF-I induced a selective
      phosphorylation of PKD, and PKD was required for mineralization. PKC/D and MAPK
      signaling also mediate Runx2 activity. Therefore, to document the implication for
      Runx2 in Osx regulation, we blocked Runx2 activity using a dominant negative
      Runx2 construct and an ubiquitination mediator for Runx2 degradation. We showed
      that blocking Runx2 activity inhibited the BMP-2-mediated induction of Osx. These
      studies implicated that multiple signaling pathways mediate Osx, a critical gene
      for osteoblast differentiation and bone formation. In addition to Runx2, other
      signaling components may be necessary to regulate Osx during osteoblast lineage
      progression.

PMID- 16000304
TI  - Multiple signals induce endoplasmic reticulum stress in both primary and
      immortalized chondrocytes resulting in loss of differentiation, impaired cell
      growth, and apoptosis.
AB  - The endoplasmic reticulum is the site of synthesis and folding of secretory
      proteins and is sensitive to changes in the internal and external environment of
      the cell. Both physiological and pathological conditions may perturb the function
      of the endoplasmic reticulum, resulting in endoplasmic reticulum stress. The
      chondrocyte is the only resident cell found in cartilage and is responsible for
      synthesis and turnover of the abundant extracellular matrix and may be sensitive
      to endoplasmic reticulum stress. Here we report that glucose withdrawal,
      tunicamycin, and thapsigargin induce up-regulation of GADD153 and caspase-12, two
      markers of endoplasmic reticulum stress, in both primary chondrocytes and a
      chondrocyte cell line. Other agents such as interleukin-1beta or tumor necrosis
      factor alpha induced a minimal or no induction of GADD153, respectively. The
      endoplasmic reticulum stress resulted in decreased chondrocyte growth based on
      cell counts, up-regulation of p21, and decreased PCNA expression. In addition,
      perturbation of endoplasmic reticulum function resulted in decreased accumulation
      of an Alcian Blue positive matrix by chondrocytes and decreased expression of
      type II collagen at the protein level. Further, quantitative real-time PCR was
      used to demonstrate a down-regulation of steady state mRNA levels coding for
      aggrecan, collagen II, and link protein in chondrocytes exposed to endoplasmic
      reticulum stress-inducing conditions. Ultimately, endoplasmic reticulum stress
      resulted in chondrocyte apoptosis, as evidenced by DNA fragmentation and annexin
      V staining. These findings have potentially important implications regarding
      consequences of endoplasmic reticulum stress in cartilage biology.

PMID- 16000305
TI  - Cooperative interactions between activating transcription factor 4 and
      Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression.
AB  - The role of ATF4 (activating transcription factor 4) in osteoblast
      differentiation and bone formation was recently described using ATF4-deficient
      mice (Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke,
      T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T. M., Hanauer, A., and
      Karsenty, G. (2004) Cell 117, 387-398). However, the mechanisms of ATF4 in bone
      cells are still not clear. In this study, we determined the molecular mechanisms
      through which ATF4 activates the mouse osteocalcin (Ocn) gene 2 (mOG2) expression
      and mOG2 promoter activity. ATF4 increased the levels of Ocn mRNA and mOG2
      promoter activity in Runx2-containing osteoblasts but not in non-osteoblastic
      cells that lack detectable Runx2 protein. However, ATF4 increased Ocn mRNA and
      mOG2 promoter activity in non-osteoblastic cells when Runx2 was co-expressed.
      Mutational analysis of the OSE1 (ATF4-binding site) and the two OSE2s (Runx2
      binding sites) in the 657-bp mOG2 promoter demonstrated that ATF4 and Runx2
      activate Ocn via cooperative interactions with these sites. Pull-down assays
      using nuclear extracts from osteoblasts or COS-7 cells overexpressing ATF4 and
      Runx2 showed that both factors are present in either anti-ATF4 and anti-Runx2
      immunoprecipitates. In contrast, pull-down assays using purified glutathione S
      transferase fusion proteins were unable to demonstrate a direct physical
      interaction between ATF4 and Runx2. Thus, accessory factors are likely involved
      in stabilizing interactions between these two molecules. Regions within Runx2
      required for ATF4 complex formation and activation were identified. Deletion
      analysis showed that the leucine zipper domain of ATF4 is critical for Runx2
      activation. This study is the first demonstration that cooperative interactions
      between ATF4 and Runx2/Cbfa1 stimulate osteoblast-specific Ocn expression and
      suggests that this regulation may represent a novel intramolecular mechanism
      regulating Runx2 activity and, thereby, osteoblast differentiation and bone
      formation.

PMID- 16000307
TI  - Mechanisms of SOCS3 phosphorylation upon interleukin-6 stimulation. Contributions
      of Src- and receptor-tyrosine kinases.
AB  - The suppressors of cytokine signaling (SOCS) are negative feedback inhibitors of
      cytokine signal transduction. SOCS3 is a key negative regulator of interleuking-6
      (IL-6) signal transduction. Furthermore, SOCS3 was shown to be phosphorylated
      upon treatment of cells with IL-2, and this has been reported to regulate its
      function and half-life. We set out to investigate whether SOCS3 phosphorylation
      may play a role in IL-6 signaling. Tyrosine-phosphorylated SOCS3 was detected
      upon treatment of mouse embryonic fibroblasts with IL-6. Interestingly, the
      observed SOCS3 phosphorylation does not require SOCS3 recruitment to
      phosphotyrosine (Tyr(P)) 759 of gp130, and the kinetics of SOCS3 phosphorylation
      do not match the activation kinetics of the Janus kinases. This suggests that
      other kinases may be involved in SOCS3 phosphorylation. Using Src and Janus
      kinase inhibitors as well as Src kinase-deficient mouse embryonic fibroblasts, we
      provide evidence that Src kinases, which we found to be constitutively active in
      these cells, are involved in the phosphorylation of IL-6-induced SOCS3. In
      addition, we found that receptor-tyrosine kinases such as platelet-derived growth
      factor receptor or epidermal growth factor receptor can very potently
      phosphorylate IL-6-induced SOCS3. Taken together, these results suggest that
      SOCS3 phosphorylation is not a JAK-mediated phenomenon but is dependent on the
      activity of other kinases such as Src kinases or receptor-tyrosine kinases, which
      can either be constitutively active or activated by an additional stimulus.

PMID- 16000308
TI  - Novel interaction partners of the CD2BP2-GYF domain.
AB  - The GYF domain of CD2BP2 serves as an adapter that recognizes proline-rich
      sequences in intracellular proteins. Although the T cell adhesion molecule CD2
      and the core splicing protein SmB/B' were previously shown to interact with
      CD2BP2-GYF, we are now using a general approach to identify putative GYF domain
      target sites within the human proteome. The phage display-derived recognition
      motif for CD2BP2-GYF is PPG(W/F/Y/M/L). SPOT analysis confirmed that the GYF
      domain interacts with peptides from human proteins containing the consensus site.
      Epitope mapping by NMR spectroscopy performed for several peptides revealed a
      conserved binding surface. A direct interaction of the CD2BP2-GYF domain with the
      novel protein interaction partners PI31 and NPWBP was verified by yeast two
      hybrid analysis.

PMID- 16000309
TI  - Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the
      phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells.
AB  - Oxidative stress activates various signal transduction pathways, including Jun N
      terminal kinase (JNK) and its substrates, that induce apoptosis. We reported here
      the role of angiopoietin-1 (Ang1), which is a prosurvival factor in endothelial
      cells, during endothelial cell damage induced by oxidative stress. Hydrogen
      peroxide (H2O2) increased apoptosis of endothelial cells through JNK activation,
      whereas Ang1 inhibited H2O2-induced apoptosis and concomitant JNK
      phosphorylation. The inhibition of H2O2-induced JNK phosphorylation was reversed
      by inhibitors of phosphatidylinositol (PI) 3-kinase and dominant-negative Akt,
      and constitutively active-Akt attenuated JNK phosphorylation without Ang1. These
      data suggested that Ang1-dependent Akt phosphorylation through PI 3-kinase leads
      to the inhibition of JNK phosphorylation. H2O2-induced phosphorylation of
      SAPK/Erk kinase (SEK1) at Thr261, which is an upstream regulator of JNK, was also
      attenuated by Ang1-dependent activation of the PI 3-kinase/Akt pathway. In
      addition, Ang1 induced SEK1 phosphorylation at Ser80, suggesting the existence of
      an additional signal transduction pathway through which Ang1 attenuates JNK
      phosphorylation. These results demonstrated that Ang1 attenuates H2O2-induced
      SEK1/JNK phosphorylation through the PI 3-kinase/Akt pathway and inhibits the
      apoptosis of endothelial cells to oxidative stress.

PMID- 16000310
TI  - Nrf2 controls constitutive and inducible expression of ARE-driven genes through a
      dynamic pathway involving nucleocytoplasmic shuttling by Keap1.
AB  - Nrf2 regulates the expression of genes encoding antioxidant proteins involved in
      cellular redox homeostasis. Previous studies have suggested that activation of
      Nrf2 is mediated by mechanisms promoting its dissociation from Keap1, a cytosolic
      repressor that acts to sequester the transcription factor in the cytoplasm. As a
      short-lived protein, Nrf2 is also activated by mechanisms leading to its
      stabilization in cells under stress, and recent evidence indicates that Keap1 has
      an active role in the control of its stability. In this report, using
      immunocytochemistry, cell fractionation, and chromatin immunoprecipitation
      analyses, we found that Nrf2 is primarily a nuclear protein and that it is
      expressed and recruited to the chromatin constitutively to drive basal gene
      expression. Furthermore, we found evidence indicating that Keap1 may repress Nrf2
      activity by transiently shuttling into the nucleus to promote its ubiquitylation.
      The data suggested that the steady-state level of Nrf2 is maintained by a dynamic
      pathway that balances its constitutive expression with a Keap1-regulated
      degradation process downstream of its role as a transcriptional activator. We
      suggest that the stabilization of Nrf2 in cells under stress represents the
      central regulatory response mediated by mechanisms that interfere with its
      interaction with Keap1, leading to the induction of antioxidant enzymes important
      to maintain cellular redox homeostasis.

PMID- 16000311
TI  - Role of phospholipase C-zeta domains in Ca2+-dependent phosphatidylinositol 4,5
      bisphosphate hydrolysis and cytoplasmic Ca2+ oscillations.
AB  - The sperm-specific phospholipase C-zeta (PLCzeta) elicits fertilization-like Ca2+
      oscillations and activation of embryo development when microinjected into
      mammalian eggs (Saunders, C. M., Larman, M. G., Parrington, J., Cox, L. J.,
      Royse, J., Blayney, L. M., Swann, K., and Lai, F. A. (2002) Development (Camb.)
      129, 3533-3544; Cox, L. J., Larman, M. G., Saunders, C. M., Hashimoto, K., Swann,
      K., and Lai, F. A. (2002) Reproduction 124, 611-623). PLCzeta may represent the
      physiological stimulus for egg activation and development at mammalian
      fertilization. PLCzeta is the smallest known mammalian PLC isozyme, comprising
      two EF hand domains, a C2 domain, and the catalytic X and Y core domains. To gain
      insight into PLCzeta structure-function, we assessed the ability of PLCzeta and a
      series of domain-deletion constructs to cause phosphatidylinositol 4,5
      bisphosphate hydrolysis in vitro and also to generate cytoplasmic Ca2+ changes in
      intact mouse eggs. PLCzeta and the closely related PLCdelta1 had similar K(m)
      values for phosphatidylinositol 4,5-bisphosphate, but PLCzeta was around 100
      times more sensitive to Ca2+ than was PLCdelta1. Notably, specific
      phosphatidylinositol 4,5-bisphosphate hydrolysis activity was retained in PLCzeta
      constructs that had either EF hand domains or the C2 domain removed, or both. In
      contrast, Ca2+ sensitivity was greatly reduced when either one, or both, of the
      EF hand domains were absent, and the Hill coefficient was reduced upon deletion
      of the C2 domain. Microinjection into intact mouse eggs revealed that all domain
      deletion constructs were ineffective at initiating Ca2+ oscillations. These data
      suggest that the exquisite Ca2+-dependent features of PLCzeta regulation are
      essential for it to generate inositol 1,4,5-trisphosphate and Ca2+ oscillations
      in intact mouse eggs.

PMID- 16000312
TI  - Crystal structure of the Yersinia enterocolitica type III secretion chaperone
      SycT.
AB  - Several Gram-negative pathogens deploy type III secretion systems (TTSSs) as
      molecular syringes to inject effector proteins into host cells. Prior to
      secretion, some of these effectors are accompanied by specific type III secretion
      chaperones. The Yersinia enterocolitica TTSS chaperone SycT escorts the effector
      YopT, a cysteine protease that inactivates the small GTPase RhoA of targeted host
      cells. We solved the crystal structure of SycT at 2.5 angstroms resolution.
      Despite limited sequence similarity among TTSS chaperones, the SycT structure
      revealed a global fold similar to that exhibited by other structurally solved
      TTSS chaperones. The dimerization domain of SycT, however, differed from that of
      all other known TTSS chaperone structures. Thus, the dimerization domain of TTSS
      chaperones does not likely serve as a general recognition pattern for downstream
      processing of effector/chaperone complexes. Yersinia Yop effectors are bound to
      their specific Syc chaperones close to the Yop N termini, distinct from their
      catalytic domains. Here, we showed that the catalytically inactive YopT(C139S) is
      reduced in its ability to bind SycT, suggesting an ancillary interaction between
      YopT and SycT. This interaction could maintain the protease inactive prior to
      secretion or could influence the secretion competence and folding of YopT.

PMID- 16000313
TI  - 15S-Lipoxygenase-2 mediates arachidonic acid-stimulated adhesion of human breast
      carcinoma cells through the activation of TAK1, MKK6, and p38 MAPK.
AB  - The dietary cis-polyunsaturated fatty acid, arachidonic acid, stimulates adhesion
      of metastatic human breast carcinoma cells (MDA-MB-435) to the extracellular
      matrix, but the molecular mechanisms by which fatty acids modify the behavior of
      these cells are unclear. Exposure to arachidonic acid activates multiple
      signaling pathways. Activation of p38 mitogen-activated protein kinase (p38 MAPK)
      is required for increased cell adhesion to type IV collagen, and this activation
      is sensitive to inhibitors of lipoxygenases, suggesting a requirement for
      arachidonic acid metabolism. The goals of the current study were to identify the
      one or more key metabolites of arachidonic acid that are responsible for
      activation of p38 MAPK and to elucidate the upstream kinases that lead to p38
      MAPK activation. High performance liquid chromatographic analysis revealed that
      MDA-MB-435 cells metabolize exogenous arachidonic acid predominantly to 15(S)
      hydroxyeicosatetraenoic acid (15(S)-HETE). Immunoblot analysis with antibodies
      specific to 15(S)-lipoxygenase-1 (LOX-1) and 15(S)-lipoxygenase-2 (LOX-2)
      demonstrated the expression of 15-LOX-2, but not 15-LOX-1, in these tumor cells.
      A LOX inhibitor, nordihydroguaiaretic acid, attenuated production of 15(S)-HETE
      and inhibited the phosphorylation of p38 MAPK following exposure to arachidonic
      acid. In contrast, overexpression of LOX-2 sensitized the cells to the addition
      of arachidonic acid, leading to increased activation of p38 MAPK. Addition of
      exogenous 15(S)-HETE to MDA-MB-435 cells stimulated cell adhesion to type IV
      collagen and activated the p38 MAPK pathway, including the upstream kinases
      transforming growth factor-beta1-activated protein kinase-1 (TAK1) and MAPK
      kinase 6. Transfection of these cells with a dominant negative form of TAK1
      blocked arachidonic acid-stimulated p38 MAPK phosphorylation. These data
      demonstrate that 15(S)-LOX-2 generation of 15(S)-HETE activates specific growth
      factor receptor-related signaling pathways, thereby initiating signal
      transduction events leading to increased cell adhesion to the extracellular
      matrix.

PMID- 16000314
TI  - Lifetime intellectual function and satisfaction with life in old age:
      longitudinal cohort study.

PMID- 16000315
TI  - Differential nonsense mediated decay of mutated mRNAs in mismatch repair
      deficient colorectal cancers.
AB  - The nonsense-mediated decay (NMD) system normally targets mRNAs with premature
      termination codons (PTCs) for rapid degradation. We investigated for a putative
      role of NMD in cancers with microsatellite instability (MSI-H cancers), because
      numerous mutant mRNAs containing PTC are generated in these tumors as a
      consequence of their mismatch repair deficiency. Using a quantitative RT-PCR
      approach in a large series of colorectal cancer cell lines, we demonstrate a
      significantly increased rate of degradation of mutant mRNAs containing a PTC
      compared with wild-type. A specific siRNA strategy was used to inhibit RENT-1
      and/or RENT-2 activity, two major genes in the NMD system. This allowed us to
      show that increased degradation of PTC-containing mRNAs in MSI-H tumors was
      partly dependent upon NMD activity. The efficiency of NMD for the degradation of
      mutant mRNAs from target genes was highly variable in these cancers. NMD degraded
      some of them (TGFssRII, MSH3, GRK4), although allowing the persistent expression
      of others (BAX, TCF-4). This is of particular interest within the context of a
      proposed conservation of biological activity for the corresponding mutated
      proteins. We thus propose that NMD might play an important role in the selection
      of target gene mutations with a functional role in MSI-H carcinogenesis.

PMID- 16000316
TI  - CHRM2 gene predisposes to alcohol dependence, drug dependence and affective
      disorders: results from an extended case-control structured association study.
AB  - Cholinergic muscarinic 2 receptor (CHRM2) is implicated in memory and cognition,
      functions impaired in many neuropsychiatric disorders. Wang et al. [Wang, J.C.,
      Hinrichs, A.L., Stock, H., Budde, J., Allen, R., Bertelsen, S., Kwon, J.M., Wu,
      W., Dick, D.M., Rice, J. et al. (2004) Evidence of common and specific genetic
      effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene
      with alcohol dependence and major depressive syndrome. Hum. Mol. Genet., 13, 1903
      1911] reported that variation in CHRM2 gene predisposed to alcohol dependence
      (AD) and major depressive syndrome. We examined the relationships between
      variation in CHRM2 and AD, drug dependence (DD) and affective disorders, using a
      novel extended case-control structured association (SA) method. Six markers at
      CHRM2 and 38 ancestry-informative markers (AIMs) were genotyped in a sample of
      871 subjects, including 333 healthy controls [287 European-Americans (EAs) and 46
      African-Americans (AAs)] and 538 AD and/or DD subjects (415 with AD and 346 with
      DD and 382 EAs and 156 AAs). The same CHRM2 markers were genotyped in a sample of
      137 EA subjects with affective disorders. All of the six markers were in Hardy
      Weinberg equilibrium in controls, but SNP3 (rs1824024) was in Hardy-Weinberg
      disequilibrium in the AD and DD groups. Using conventional case-control
      comparisons, some markers were nominally significantly or suggestively associated
      with phenotypes before or after controlling for population stratification and
      admixture effects, but these associations were not significant after multiple
      test correction. However, regression analysis identified specific alleles,
      genotypes, haplotypes and diplotypes that were significantly associated with risk
      for each disorder. We conclude that variation in CHRM2 predisposes to AD, DD and
      affective disorders. One haplotype block within the 5'-UTR of CHRM2 may be more
      important for the development of these disorders than other regions. Interaction
      between two specific alleles within this block and interaction between two
      specific diplotypes covering this block multiplicatively increased risk for AD
      and DD. Although interaction between these two diplotypes also increased risk for
      affective disorders, the magnitude of the increased risk was less than the sum of
      the individual risks. In addition, a specific diplotype might inversely affect
      risk for AD and DD and risk for affective disorders.

PMID- 16000317
TI  - The H1c haplotype at the MAPT locus is associated with Alzheimer's disease.
AB  - Although it is clear that microtubule associated protein tau (MAPT) is involved
      in Alzheimer's disease (AD) pathology, it has not been clear whether it is
      involved genetically. We have recently examined the MAPT locus in progressive
      supranuclear palsy and found that a haplotype (H1c) on the background of the well
      described H1 clade is associated with PSP. Here we report that the same haplotype
      is associated with the risk of AD in two autopsy confirmed series of cases with
      ages at death >65 years.

PMID- 16000318
TI  - ER retention and degradation as the molecular basis underlying Gaucher disease
      heterogeneity.
AB  - Gaucher disease (GD), an autosomal recessive disease, is characterized by
      accumulation of glucosylceramide mainly in cells of the reticuloendothelial
      system, due to mutations in the acid beta-glucocerebrosidase gene. Some of the
      patients suffer from neurological symptoms (type 2 and type 3 patients), whereas
      patients with type 1 GD do not present neurological signs. The disease is
      heterogeneous even among patients with the same genotype, implicating that a
      mutation in the glucocerebrosidase gene is required to cause GD but other factors
      play an important role in the manifestation of the disease. Glucocerebrosidase is
      a lysosomal enzyme, synthesized on endoplasmic reticulum (ER)-bound polyribosomes
      and translocated into the ER. Following N-linked glycosylations, it is
      transported to the Golgi apparatus, from where it is trafficked to the lysosomes.
      In this study, we tested glucocerebrosidase protein levels, N-glycans processing
      and intracellular localization in skin fibroblasts derived from patients with GD.
      Our results strongly suggest that mutant glucocerebrosidase variants present
      variable levels of ER retention and undergo ER-associated degradation in the
      proteasomes. The degree of ER retention and proteasomal degradation is one of the
      factors that determine GD severity.

PMID- 16000319
TI  - Profound ataxia in complexin I knockout mice masks a complex phenotype that
      includes exploratory and habituation deficits.
AB  - Complexins are presynaptic proteins that bind to the SNARE complex where they
      modulate neurotransmitter release. A number of studies report changes in
      complexins in psychiatric (schizophrenia and depression) and neurodegenerative
      disorders (Huntington's disease, Wernicke's encephalopathy and Parkinson's
      disease). Here, we characterize the behavioural phenotype of Cplx1 knockout
      (Cplx1-/-) mice. Cplx1-/- mice develop a strong ataxia in the absence of
      cerebellar degeneration. Although originally reported to die within 2-4 months
      after birth, when reared using an enhanced feeding regime, these mice survive
      normally (i.e. >2 years). Cplx1-/- mice show pronounced deficits in motor
      coordination and locomotion including abnormal gait, inability to run or swim,
      impaired rotarod performance, reduced neuromuscular strength, dystonia and
      resting tremor. Although the abnormal motor phenotype dominates their overt
      symptoms, Cplx1-/- mice also show other behavioural deficits, particularly in
      complex behaviours. They have deficits in grooming and rearing behaviour and show
      reduced exploration in several different paradigms. They also show deficits in
      tasks reflecting emotional reactivity. They fail to habituate to confinement and
      show a 'panic' response when exposed to water. The abnormalities seen in the
      behaviour of Cplx1-/- mice reflect those predicted from the distribution of
      complexin I in the brain. Our data show that complexin I is essential not only
      for normal motor function in mice, but also for normal performance of other
      complex behaviours. These results support the idea that altered expression of
      complexins in disease states may contribute to the symptomatology of disorders in
      which they are dysregulated.

PMID- 16000320
TI  - Allelic association of the human homologue of the mouse modifier Ptprj with
      breast cancer.
AB  - Human homologues of mouse cancer modifier genes may play a role in cancer risk
      and prognosis. A proportion of the familial risk of common cancers may be
      attributable to variants in such genes, each contributing to a small effect. The
      protein tyrosine phosphatase receptor type J (PTPRJ) has been recently identified
      as being the protein encoded by the Scc1 mouse gene (susceptibility to colon
      cancer-1). In addition, the PTPRJ gene has been shown to be somatically altered
      in several human cancer types such as colon, lung and breast cancers and to have
      the characteristics of a tumour-suppressor gene. The purpose of this study was to
      determine whether common variants in the PTPRJ gene represent low penetrance
      breast cancer susceptibility alleles. To test this hypothesis, we assessed single
      nucleotide polymorphisms (SNPs) tagging the common SNPs and haplotypes of the
      gene in 4512 cases and 4554 controls from the East Anglian population. We
      observed a difference in the haplotype frequency distributions between cases and
      controls (P = 0.0023, OR = 0.81 [0.72-0.92]). Thus, carrying a specific PTPRJ
      haplotype confers a protective effect on the risk of breast cancer. This result
      establishes the principle that mouse cancer modifier genes are candidates for low
      penetrance human breast cancer susceptibility genes.

PMID- 16000321
TI  - Somatodendritic accumulation of misfolded SOD1-L126Z in motor neurons mediates
      degeneration: alphaB-crystallin modulates aggregation.
AB  - Mice expressing variants of superoxide dismutase-1 (SOD1) encoding C-terminal
      truncation mutations linked to familial amyotrophic lateral sclerosis (FALS) have
      begun to define the role of misfolding and aggregation in the pathogenesis of
      disease. Here, we examine transgenic mice expressing SOD1-L126Z (Z = stop
      truncation of last 28 amino acids), finding that detergent-insoluble mutant
      protein specifically accumulates in somatodendritic compartments. Soluble forms
      of the SOD1-L126Z were virtually undetectable in spinal cord at any age and the
      levels of accumulated protein directly correlated with disease symptoms. Neither
      soluble nor insoluble forms of SOD1-L126Z were transported to distal axons. In
      vitro, small heat shock protein (Hsp) alphaB-crystallin suppressed the in vitro
      aggregation of SOD1-L126Z. In vivo, alphaB-crystallin immunoreactivity was most
      abundant in oligodendrocytes and up-regulated in astrocytes of symptomatic mice;
      neither of these cell-types accumulated mutant SOD1 immunoreactivity. These
      results suggest that damage to motor neuron cell bodies and dendrites within the
      spinal cord can be sufficient to induce motor neuron disease and that the
      activities of chaperones may modulate the cellular specificity of mutant SOD1
      accumulation.

PMID- 16000322
TI  - Alms1-disrupted mice recapitulate human Alstrom syndrome.
AB  - Mutations in the human ALMS1 gene cause Alstrom syndrome (AS), a progressive
      disease characterized by neurosensory deficits and by metabolic defects including
      childhood obesity, hyperinsulinemia and Type 2 diabetes. Other features that are
      more variable in expressivity include dilated cardiomyopathy,
      hypertriglyceridemia, hypercholesterolemia, scoliosis, developmental delay and
      pulmonary and urological dysfunctions. ALMS1 encodes a ubiquitously expressed
      protein of unknown function. To obtain an animal model in which the etiology of
      the observed pathologies could be further studied, we generated a mouse model
      using an Alms1 gene-trapped ES cell line. Alms1-/- mice develop features similar
      to patients with AS, including obesity, hypogonadism, hyperinsulinemia, retinal
      dysfunction and late-onset hearing loss. Insulin resistance and increased body
      weight are apparent between 8 and 12 weeks of age, with hyperglycemia manifesting
      at approximately 16 weeks of age. In addition, Alms1-/- mice have normal hearing
      until 8 months of age, after which they display abnormal auditory brainstem
      responses. Diminished cone ERG b-wave response is observed early, followed by the
      degeneration of photoreceptor cells. Electron microscopy revealed accumulation of
      intracellular vesicles in the inner segments of photoreceptors, whereas
      immunohistochemical analysis showed mislocalization of rhodopsin to the outer
      nuclear layer. These findings suggest that ALMS1 has a role in intracellular
      trafficking.

PMID- 16000324
TI  - Up-regulation of the ubiquitous alternative splicing factor Tra2beta causes
      inclusion of a germ cell-specific exon.
AB  - We have discovered a new exon of the homeodomain-interacting kinase HipK3 that
      incorporates a premature stop codon and is included only in the human testis. To
      investigate this, we tested the effects of transfecting cells with green
      fluorescent protein fusions of RNA-binding proteins implicated in spermatogenesis
      using a novel assay based on multi-fraction fluorescence-activated cell sorting
      (MF-FACS). This allows the effect of a controlled titration of any splicing
      factor on the splicing of endogenous genes to be studied in vivo. We found that
      Tra2beta recapitulates testis-specific splicing of endogenous HipK3 in a
      concentration-dependent manner and binds specifically to a long purine-rich
      sequence in the novel exon. This sequence was also specifically bound by hnRNP
      A1, hnRNP H, ASF/SF2 and SRp40, but not by 9G8. Consistent with these
      observations, in vitro studies showed that this sequence shifts splicing to a
      downstream 5' splice site within a heterologous pre-mRNA substrate in the
      presence of Tra2beta, ASF/SF2 and SRp40, whereas hnRNP A1 specifically inhibits
      this choice. By mutating the purine-rich sequence in the context of the HipK3
      gene, we also show that it is the major determinant of Tra2beta- and hnRNP A1
      mediated regulation. Tra2 is essential for sex determination and spermatogenesis
      in flies, and Tra2beta protein was most highly expressed in testis out of six
      mouse tissues, whereas hnRNP A1 is down-regulated during germ cell development.
      Therefore, our data imply an evolutionarily conserved role for Tra2 proteins in
      spermatogenesis and suggest that an elevated concentration of Tra2beta may
      convert it into a tissue-specific splicing factor.

PMID- 16000325
TI  - Are anti-smoking parenting practices related to adolescent smoking cognitions and
      behavior?
AB  - The aim of this study was to explain the effects of anti-smoking parenting
      practices on adolescent smoking cognitions and behavior by showing the mediating
      effects of cognitions. Data were gathered among Dutch high school students in the
      control condition of the European Smoking prevention Framework Approach (ESFA).
      Anti-smoking parenting practices were measured by parental reactions to smoking,
      house rules, and frequency and content of communication about smoking. Attitudes,
      perceived social influences and self-efficacy made up for smoking cognitions.
      Additionally, intention to smoke was measured. Relations between practices and
      cognitions were mostly significant. While some practices were associated with
      less smoking (communication about health risks of smoking, health risks of
      breathing in smoke, addictive qualities of smoking and attention for smoking in
      school), others were related to increased chances of smoking (rewards for not
      smoking, frequency of communication about smoking, communication about being
      allowed to smoke, price of cigarettes and friends smoking). The effects of
      parenting hardly varied by parental smoking status or adolescent gender. Several
      practices operated through cognitions, which was more pronounced in older
      adolescents. Counter-productive effects of practices and the few effects in the
      longitudinal analyses indicate that the order in which parents and adolescents
      influence each other should be examined more closely.

PMID- 16000323
TI  - Whole genome association study of rheumatoid arthritis using 27 039
      microsatellites.
AB  - A major goal of current human genome-wide studies is to identify the genetic
      basis of complex disorders. However, the availability of an unbiased, reliable,
      cost efficient and comprehensive methodology to analyze the entire genome for
      complex disease association is still largely lacking or problematic. Therefore,
      we have developed a practical and efficient strategy for whole genome association
      studies of complex diseases by charting the human genome at 100 kb intervals
      using a collection of 27,039 microsatellites and the DNA pooling method in three
      successive genomic screens of independent case-control populations. The final
      step in our methodology consists of fine mapping of the candidate susceptible DNA
      regions by single nucleotide polymorphisms (SNPs) analysis. This approach was
      validated upon application to rheumatoid arthritis, a destructive joint disease
      affecting up to 1% of the population. A total of 47 candidate regions were
      identified. The top seven loci, withstanding the most stringent statistical
      tests, were dissected down to individual genes and/or SNPs on four chromosomes,
      including the previously known 6p21.3-encoded Major Histocompatibility Complex
      gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis
      complemented by end stage SNP typing provides a new tool for genetic dissection
      of multifactorial pathologies including common diseases.

PMID- 16000326
TI  - Expression and function of TNF family member B cell-activating factor in the
      development of autoimmune arthritis.
AB  - B cell-activating factor (BAFF), a member of tumor necrosis factor family
      cytokines, has been shown to enhance the maturation and survival of peripheral B
      cells. While BAFF is implicated in regulating B cell function and autoimmunity,
      its role in the development of autoimmune arthritis has not been fully clarified.
      Using a collagen-induced arthritis (CIA) mouse model, we detected dysregulated
      expression of BAFF and its receptors in the peripheral lymphoid organs during
      arthritis induction. Elevated serum levels of BAFF were closely correlated with
      increased levels of anti-collagen antibodies during the CIA progression.
      Moreover, dendritic cells (DCs) and macrophages were found to express high amount
      of BAFF proteins at the acute and chronic stages of CIA, respectively. In
      cultures, recombinant BAFF suppressed apoptosis of splenic B cells from arthritic
      mice, and DC-induced B cell proliferation was specifically blocked by soluble
      decoy receptor B cell maturation antigen-Fc. These findings suggest that
      overproduction of BAFF by DCs and macrophages may play a crucial role in the
      pathogenesis of experimental arthritis.

PMID- 16000327
TI  - Stress as an endogenous adjuvant: augmentation of the immunization phase of cell
      mediated immunity.
AB  - Stress is thought to be immunosuppressive but paradoxically exacerbates
      inflammatory and autoimmune diseases. We initially showed that acute stress
      enhances skin immunity. Such immunoenhancement could promote immunoprotection in
      case of wounding, infection or vaccination but could also exacerbate
      immunopathological diseases. Here we identify the molecular and cellular
      mediators of the immunoenhancing effects of acute stress. Compared with non
      stressed mice, acutely stressed animals showed significantly greater pinna
      swelling and leukocyte infiltration, and up-regulated macrophage chemoattractant
      protein-1, macrophage inflammatory protein-3alpha, IL-1alpha, IL-1beta, IL-6,
      tumor necrosis factor-alpha and IFN-gamma, but not IL-4 gene expression at the
      site of primary antigen exposure. Stressed animals also showed enhanced
      maturation and trafficking of dendritic cells (DCs) from skin to lymph nodes
      (LNs), higher numbers of activated macrophages in skin and LNs, increased T cell
      activation in LNs, and enhanced recruitment of surveillance T cells to skin.
      These findings show that important interactive components of innate (DCs and
      macrophages) and adaptive (surveillance T cells) immunity are mediators of the
      stress-induced enhancement of a primary immune response. Such enhancement during
      primary immunization may induce a long-term increase in immunologic memory
      resulting in subsequent augmentation of the immune response during secondary
      antigen exposure. Thus, the evolutionarily adaptive fight-or-flight stress
      response may protectively prepare the immune system for impending danger (e.g.
      infection and wounding by a predator), but may also contribute to stress-induced
      exacerbation of inflammatory and autoimmune diseases.

PMID- 16000328
TI  - The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non
      peptide chemokine receptor antagonist protects mice from dextran sodium sulfate
      mediated colitis.
AB  - Chemokine receptors CCR2, CCR5 and CXCR3 are involved in the regulation of
      macrophage- and T cell-mediated immune responses and in the migration and
      activation of these cells. In order to determine whether blockade of these
      chemokine receptors modulates intestinal inflammation, we investigated here the
      effect of a non-peptide chemokine receptor antagonist, TAK-779 (N,N-dimethyl-N-[4
      [[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]
      tetrahydro-2H-pyran-4-aminium chloride), in mice with dextran sodium sulfate
      (DSS)-induced experimental colitis. C57BL/6 mice were fed 5% DSS in their
      drinking water for up to 7 days with or without the administration of TAK-779.
      The severity of inflammation in the colon was assessed by clinical signs and
      histological examination. Infiltration of inflammatory cells into the mucosa was
      analyzed by immunohistochemistry, and the expression of cytokine and chemokine
      mRNAs in tissues was quantitated by reverse transcription-PCR. During DSS-induced
      colitis, the recruitment of monocytes/macrophages into the colonic mucosa and the
      induction of proinflammatory cytokines correlated with the severity of intestinal
      inflammation. The onset of clinical signs and histopathologic features were
      delayed in animals treated with TAK-779. The expression of CCR2, CCR5 and CXCR3
      mRNAs was inhibited in the TAK-779-treated mice. Consistent with these results,
      infiltration of monocytes/macrophages into the lamina propria was almost
      completely inhibited and the expression of colonic IL-1beta and IL-6 was
      significantly decreased in the TAK-779-treated mice. The blockade of CCR2, CCR5
      and CXCR3 prevents murine experimental colitis by inhibiting the recruitment of
      inflammatory cells into the mucosa. Therefore, chemokines and their receptors may
      be therapeutic targets for the treatment of inflammatory bowel disease.

PMID- 16000329
TI  - Attenuated pathogenesis of polymicrobial peritonitis in mice after TLR2 agonist
      pre-treatment involves ST2 up-regulation.
AB  - The innate immune system uses Toll-like receptors (TLRs) to activate and instruct
      immune responses against microbial pathogens. Administration of TLR agonists to
      mice induces a state of hyporesponsiveness, or tolerance, characterized by
      reduced cytokine production upon subsequent second challenge. The present study
      examined the effects of pre-treatment of mice with TLR2-dependent stimuli on the
      host defense against acute polymicrobial infection. Immune priming of mice with
      macrophage-activating lipopeptide-2 (MALP-2) 4 days prior to infection greatly
      improves survival and bacterial clearance in a model of polymicrobial septic
      peritonitis which is associated with enhanced accumulation of effector
      neutrophils in the peritoneal cavity. Further, the systemic and local production
      of both myeloid differentiation factor 88 (MyD88)-dependently and MyD88
      independently produced cytokines was substantially diminished, but not completely
      absent, in TLR2-treated mice. While pre-treatment with MALP-2 does not involve
      differential expression of TLR and IL-1R-associated kinase proteins, ST2, a
      negative regulator of TLR signaling, was up-regulated after treatment of mice
      with either MALP-2 or N-alpha-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-L
      cysteine. Therefore, ST2 may be a mechanism, among others, to attenuate the
      sepsis-induced cytokine burst. Thus, these results suggest that immune protection
      in mice after pre-treatment with TLR2-dependent stimuli involves the induction of
      enhanced pathogen defense by neutrophils. In addition, up-regulation of ST2 could
      contribute to the diminished cytokine production.

PMID- 16000330
TI  - Asthmatic changes in mice lacking T-bet are mediated by IL-13.
AB  - Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway
      hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2
      cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition
      and myofibroblast transformation. Here we analyze the mechanisms responsible for
      the chronic airway remodeling observed in these mice. CD4+ T cells isolated from
      the lung of T-bet-deficient mice were spontaneously activated
      CD44(high)CD69(high) memory T cells, with a typical T(h)2 cytokine profile.
      Neutralization of IL-13 but not IL-4 resulted in amelioration of AHR in airways
      of mice lacking T-bet. IL-13 blockade also led to reduced eosinophilia and
      decreased vimentin, transforming growth factor beta (TGF-beta) and alpha smooth
      muscle actin (alphaSMA) levels. T-bet(-/-) lung fibroblasts proliferated very
      rapidly and released increased amounts of TGF-beta. Interestingly, neutralization
      of TGF-beta ameliorated aspects of the chronic airway remodeling phenotype but
      did not reduce AHR. These data highlight a T-bet-directed function for IL-13 in
      controlling lung remodeling that is both dependent on and independent of its
      interaction with TGF-beta in the asthmatic airway.

PMID- 16000331
TI  - A negative regulatory element in the rabbit 3'IgH chromosomal region.
AB  - Mouse and human IgH loci contain several 3'IgH enhancers. In rabbit, a single
      hs1,2 enhancer is located 3' of the distal germ line Calpha gene, Calpha13. We
      searched for additional regulatory elements in this region by using a luciferase
      reporter assay and nucleotide sequence analysis. Within 8 kb 3' of Calpha13, we
      identified a 1-kb fragment that negatively regulated the hs1,2 enhancement of the
      Ialpha promoter. This negative regulatory element, Calpha-NRE, contains a
      conserved 300-bp region that is associated with 8 of the 13 germ line Calpha
      genes. This conserved region contains an E box that, by electrophoretic mobility
      shift assay, binds an E47-like protein. At the 5' end, Calpha-NRE also includes a
      270-bp region with 20-bp repeats nearly identical to those 3' of mouse and human
      Calpha genes, and these repeats bind unidentified nuclear protein(s). Calpha-NRE
      appears to be a novel regulatory element that may contribute to the regulation of
      IgH gene expression.

PMID- 16000332
TI  - A glycoprotein endopeptidase enhances calcium influx and cytokine production by
      CD4+ T cells of old and young mice.
AB  - Many of the downstream signaling defects observed in aged T cells are believed to
      be the result of very early events involving the initial interaction between T
      cells and antigen-presenting cells. Recent findings suggest that this interaction
      is hindered by glycosylated surface macromolecules, including CD43, on the T cell
      surface. Treatment of CD4+ T cells by O-sialoglycoprotein endopeptidase (OSGE),
      which cleaves glycosylated forms of CD43, restores the ability of cells from aged
      mice to form immunological synapses and to express early activation markers. Here
      we show that OSGE enhances Ca2+ influx in T cells from CB6F1 mice, and enhances
      their ability to produce IL-2, IL-4, IL-5, IL-6, IL-10, IL-13 and IFNgamma at the
      mRNA level, and IL-2 and IFNgamma at the protein level, in the first 6 h after
      activation. Although OSGE has little effect on synapse formation in CD4+ T cells
      from young mice, our new data show that OSGE increases the production of most
      cytokines by young as well as old T cells. Secretion of the T(h)2 cytokine, IL-4,
      was altered only slightly by OSGE treatment, suggesting that the removal of OSGE
      sensitive surface molecules may have differential effects on T(h)1 and T(h)2
      cytokines. These data support a model in which O-glycosylated surface proteins
      inhibit CD4+ lymphocyte activation in both young and old mice, and in which such
      glycoproteins contribute to the age-related decline in cytokine production.

PMID- 16000333
TI  - Follow-up screening after subarachnoid haemorrhage: frequency and determinants of
      new aneurysms and enlargement of existing aneurysms.
AB  - Intracranial aneurysms have long been considered a once in a lifetime event.
      Nevertheless, patients who survive after subarachnoid haemorrhage (SAH) may be at
      risk for new aneurysms. In a cohort of patients with clipped aneurysms, we
      studied the yield of screening in the years after the SAH and we tried to
      identify risk factors for formation of new aneurysms as well as for enlargement
      of aneurysms that were already present at the time of the SAH. We screened 610
      patients who had been admitted between 1985 and 2001 for SAH by means of CT
      angiography. Risk factors were evaluated by Cox regression analyses. With
      screening we detected 129 aneurysms in 96 (16%) patients, after a mean interval
      of 8.9 years. Of these, 24 (19%) were located at the site of the previously
      ruptured and clipped aneurysm and 105 (81%) at a site remote from the clip site.
      Of the aneurysms at a remote site 59 could be compared with the initial (CT)
      angiogram. Of these, 19 were truly de novo (32%) and 40 (68%) were already
      visible in retrospect. Of the 53 aneurysms that were followed over time 13 (25%)
      had enlarged. Risk factors for aneurysm formation and growth were presence of
      multiple aneurysms at time of SAH (HR 3.2, 95% CI 1.2-8.6), current smoking (HR
      3.8, 95% CI 1.5-9.4) and hypertension (HR 2.3, 95% CI 1.1-4.9). These results
      suggest that intracranial aneurysms should not be considered as a single event in
      a lifetime but rather as a continuous process. Patients with a previous SAH have
      a substantial risk for new aneurysm formation and enlargement of untreated
      aneurysms. Screening these patients might be beneficial, especially in patients
      with multiple aneurysms, hypertension and a history of smoking. The risks and
      benefits of screening, however, should be carefully weighed, for example, in a
      decision model.

PMID- 16000334
TI  - Spinocerebellar ataxia type 2: polyQ repeat variation in the CACNA1A calcium
      channel modifies age of onset.
AB  - Nine neurodegenerative diseases, collectively referred to as polyglutamine
      (polyQ) diseases, are caused by expansion of a coding CAG DNA trinucleotide
      repeat. PolyQ diseases show a strong inverse correlation between CAG repeat
      length and age of disease onset (AO). Despite this, individuals with identical
      repeat expansion alleles can have highly variable disease onset indicating that
      other factors also influence AO. We examined AO in 148 individuals in 57 sibships
      from the SCA2 founder population in Cuba. The mutant CAG repeat allele explained
      57% of AO variance. To estimate heritability of the residual variance after
      correction for SCA2 repeat length, we applied variance component analysis and
      determined the coefficient of intraclass correlation. We found that 55% of the
      residual AO variance was familial. To test candidate modifier alleles in this
      population, we selected 64 unrelated individuals from a set of 394 individuals
      who were highly discordant for AO after correction for SCA2 CAG repeat length. We
      hypothesized that long normal alleles in the other 8 polyQ disease genes were
      associated with premature disease onset in SCA2. Of the 8 genes tested, only long
      normal CAG repeats in the CACNA1A gene were associated with disease onset earlier
      than expected based on SCA2 CAG repeat size using non-parametric tests for
      alleles (P < 0.04) and genotypes (P < 0.023) after correction for multiple
      comparisons. CACNA1A variation explained 5.8% of the residual variation in AO.
      The CACNA1A calcium channel subunit represents an excellent candidate as a
      modifier of disease in SCA2. It is highly expressed in Purkinje cells (PCs) and
      is essential for the generation of the P/Q current and the complex spike in PCs.
      In contrast to other polyQ proteins, which are nuclear, the CACNA1A and SCA2
      proteins are both cytoplasmic. Furthermore, small pathologic expansions of the
      polyQ domain in the CACNA1A protein lead to PC degeneration in SCA6. Future
      studies are needed to determine whether the modifier effect of CACNA1A relates to
      neuronal dysfunction or cell death of Purkinje neurons.

PMID- 16000335
TI  - Vivid dreams, hallucinations, psychosis and REM sleep in Guillain-Barre syndrome.
AB  - We conducted a prospective controlled study of the clinical and biological
      determinants of the mental status abnormalities in 139 patients with Guillain
      Barre syndrome (GBS) and 55 patients without GBS placed in the intensive care
      unit (ICU controls). There were mental status changes in 31% of GBS patients and
      in 16% of controls (odds ratio = 2.3; P = 0.04). In GBS patients, they included
      vivid dreams (19%), illusions (30%, including an illusory body tilt),
      hallucinations (60%, mainly visual) and delusions (70%, mostly paranoid). They
      appeared a median 9 days after disease onset (range 1-40 days, during the
      progression or the plateau of the disease), and lasted a median 8 days. Seven
      (16%) patients experienced the symptoms before their admission to the ICU.
      Hallucinations were frequently hypnagogic, occurring as soon as the patients
      closed their eyes. Autonomic dysfunction, assisted ventilation and high CSF
      protein levels were significant risk factors for abnormal mental status in GBS
      patients. CSF hypocretin-1 (a hypothalamic neuropeptide deficient in narcolepsy)
      levels, measured in 20 patients, were lower in GBS patients with hallucinations
      (555 +/- 132 pg/ml) than in those without (664 +/- 71 pg/ml, P = 0.03). Since the
      mental status abnormalities had dream-like aspects, we examined their association
      with rapid eye movement sleep (REM sleep) using continuous sleep monitoring in 13
      GBS patients with (n = 7) and without (n = 6) hallucinations and 6 tetraplegic
      ICU controls without hallucinations. Although sleep was short and fragmented in
      all groups, REM sleep latency was shorter in GBS patients with hallucinations (56
      +/- 115 min) than in GBS patients without hallucinations (153 +/- 130 min) and in
      controls (207 +/- 179 min, P < 0.05). In addition, sleep structure was highly
      abnormal in hallucinators, with sleep onset in REM sleep periods (83%), abnormal
      eye movements during non-REM sleep (57%), high percentages of REM sleep without
      atonia (92 +/- 22%), REM sleep behaviour disorders and autonomic dysfunction
      (100%), reminiscent of a status dissociatus. The sleep abnormalities, that were
      almost absent in non-hallucinated GBS patients, were not exclusively related to
      ICU conditions, since they also appeared out of ICU, and were reversible,
      disappearing when the mental status abnormalities vanished while the patients
      were still in ICU. In conclusion, the mental status abnormalities experienced by
      GBS patients are different from the ICU delirium, are strongly associated with
      autonomic dysfunction, severe forms of the disease and possibly with a transitory
      hypocretin-1 transmission decrease. Sleep studies suggest that mental status
      abnormalities are wakeful dreams caused by a sleep and dream-associated disorder
      (status dissociatus).

PMID- 16000336
TI  - Alpha-synuclein redistributes to neuromelanin lipid in the substantia nigra early
      in Parkinson's disease.
AB  - The distribution and tempo of neuronal loss in Parkinson's disease correlates
      poorly with the characteristic and more widely spread intracellular changes
      associated with the disease process (Lewy bodies and Lewy neurites). To determine
      early intracellular changes in regions where cell loss is most marked
      (dopaminergic A9 substantia nigra) versus regions with Lewy bodies but where cell
      loss is limited, we assessed 13 patients with definite Parkinson's disease at
      various disease stages in comparison with controls. Using immunohistochemistry
      for alpha-synuclein, we confirmed the concentration of this protein in the soma
      of normal A9 neurons and in Lewy body pathology in brainstem catecholamine
      neurons in Parkinson's disease. Analysis of the degree of cell loss in brainstem
      catecholamine cell groups revealed that only the A9 substantia nigra had
      consistent significant cell loss early in the disease course with greater A9 cell
      loss correlating with increasing disease duration. To assess the earliest
      intracellular changes differentiating neurons more likely to degenerate,
      pigmented A9 and A10 neurons with and without obvious pathology were targeted,
      cell size and pigment density measured, and intracellular changes in alpha
      synuclein location and lipid components analysed at both the light and electron
      microscope levels. There were no changes observed in healthy A10 neurons in
      Parkinson's disease compared with controls. Pigmented A9 neurons in later stages
      of degeneration with obvious Lewy body formation had a significant reduction in
      intracellular pigment, as previously described. In contrast, A9 neurons of normal
      morphological appearance and no characteristic pathology in Parkinson's disease
      exhibited significantly increased pigment density associated with a concentration
      of alpha-synuclein to the lipid component of the pigment and a loss of associated
      cholesterol. These changes in vulnerable but apparently healthy A9 neurons
      occurred without any change in cell size or in the amount of intracellular
      pigment compared with controls. The increase in pigment density is consistent
      with previously reported increases associated with oxidation and iron loading,
      reactions known to precipitate alpha-synuclein. The selectivity of the changes
      observed in A9 nigral neurons suggests that these early intracellular changes
      predispose these neurons to more rapid cell loss in Parkinson's disease. The
      increased concentration of neuronal alpha-synuclein and pigment in normal A9
      neurons may already predispose these neurons to precipitate alpha-synuclein
      around pigment-associated lipid under oxidative conditions. Overall, these
      changes may trigger a cascade of events leading to larger intracellular
      aggregates of alpha-synuclein and the dispersement of protective pigment to
      precipitate cell death in Parkinson's disease.

PMID- 16000337
TI  - The pathological basis of semantic dementia.
AB  - Semantic dementia is a syndrome of progressive deterioration in semantic memory
      (knowledge of objects, people, concepts and words). It falls within the clinical
      spectrum of frontotemporal dementia but its pathology is yet to be studied
      systematically. This study included 18 consecutive post mortem cases meeting
      clinical criteria for semantic dementia. Clinic records and diagnostic
      histopathology were available for all cases; structural neuroimaging,
      neuropsychology and semi-quantitative histopathology/immunohistochemistry data
      were analysed where possible. The pathological diagnosis in a clear majority of
      cases was frontotemporal degeneration with ubiquitin inclusions (n = 13). Eleven
      of these cases had characteristic motor neuron disease-type inclusions in the
      dentate gyrus and cerebral cortex. Ubiquitin inclusions were found only in the
      inferior olivary nucleus in the other two, one of which was the only case to show
      degeneration of motor tracts and also to have shown evidence of motor neuron
      disease during life. None of the patients had motor symptoms or signs at
      presentation. A family history of motor neuron disease was documented in one
      case. Pick body-positive Pick's disease appeared three times. Two cases had
      Alzheimer's disease and significant coincidental Alzheimer-type pathology was
      also found in one of the ubiquitin inclusion cases. One of the Alzheimer's
      disease patients had changes in white matter signal on scanning, whereas all
      other scans showed cerebral atrophy only. Semi-quantitative assessment of
      regional neuronal loss found that anterior and inferior temporal regions bore the
      brunt of disease across all histopathological subtypes, usually on the left side,
      implicating this region in semantic processing.

PMID- 16000338
TI  - Independent patterns of damage within magno-, parvo- and koniocellular pathways
      in Parkinson's disease.
AB  - Sensory deficits have been documented in Parkinson's disease, in particular
      within the visual domain. However, ageing factors related to the brain and to
      neural and non-neural ocular structures could explain some of the previously
      reported results, in particular the claimed impairment within the koniocellular
      pathway. This study addressed visual impairment attributable to the magno-
      (luminance), parvo- (red-green) and koniocellular (blue-yellow) pathways in a
      population of Parkinson's disease patients. To avoid potentially confounding
      factors, all subjects underwent a full neurophthalmological assessment which led
      to exclusion of subjects with increased intraocular pressure, diabetes even in
      the absence of retinopathy, and ocular abnormalities (from a total of 72
      patients' eyes, 12 were excluded). Both parvo- and koniocellular pathways were
      studied by means of contrast sensitivity (CS) measurements along protan, tritan
      and deutan axes and also by fitting chromatic discrimination ellipses using eight
      measured contrast axes. Magnocellular function was assessed, using stimuli that
      induce a frequency doubling illusion, in 17 locations in the fovea and periphery.
      Achromatic (luminance modulation) thresholds were significantly higher in
      Parkinson's disease both in foveal and peripheral locations. A significant
      impairment was observed along protan and deutan axes, but only marginally along
      the tritan axis. These results were corroborated by a significant elongation of
      chromatic discrimination ellipses in our Parkinson's disease group. Correlation
      analysis showed that achromatic and chromatic CS measures were independent, which
      implies that multiple visual pathways are affected independently in Parkinson's
      disease. Magnocellular impairment was significantly correlated with age and
      disease stage, in contrast to the measured chromatic deficits. We conclude that
      in Parkinson's disease, independent damage occurs in the early magno- and
      parvocellular pathways. Furthermore, traditional koniocellular probing strategies
      in Parkinson's disease may be confounded by ageing factors, which may reconcile
      the previously reported controversial findings concerning chromatic impairment in
      Parkinson's disease.

PMID- 16000339
TI  - Cisplatin and gemcitabine in malignant mesothelioma.

PMID- 16000340
TI  - Perceptions of community participation and health gain in a community project for
      the South Asian population: a qualitative study.
AB  - BACKGROUND: The new public health rejects old individualist attempts at improving
      health and embraces community-based approaches in reducing health inequalities.
      Primary Care Trusts in England face the challenge of converting community
      participation in health into reality. This study explores differences in
      perception of participation between lay and professional stakeholders of a
      community health project for a South Asian population in Greater Manchester.
      METHODS: In-depth interviews and focus groups were used to explore the views of
      professional and lay stakeholders. All data were audio-taped, transcribed and
      analysed for emerging themes using a qualitative framework. RESULTS:
      Professionals talked of working in partnership with the community but lay
      stakeholders did not feel that they had control over the project. There were
      problems in engaging the community and local health professionals in the project.
      Lack of cultural awareness hampered participation in the project. There was
      agreement that the project improved the self-confidence of participants and
      created a more informed population. However, there was little support for claims
      of improvements in social cohesion and changes in lifestyle directly as a result
      of the project. CONCLUSION: Converting the rhetoric of community participation in
      health into reality is a greater challenge than was envisaged by policy makers.
      Marginalized communities may not be willing participants and issues of language
      and cultural sensitivity are important. Project outcomes need to be agreed to
      ensure projects are evaluated appropriately. Projects with South Asian
      communities should not be seen to be dealing with all 'ethnic health' issues
      without addressing changes in statutory organizations and other wider social
      determinants of health.

PMID- 16000341
TI  - An investigation into GPs with high patient mortality rates: a retrospective
      study.
AB  - BACKGROUND: As part of the work of the Shipman Inquiry, five general
      practitioners (GPs) in West Sussex were identified as having excessively high
      mortality rates. The aim of this study was to identify reasons for the higher
      than-expected mortality rates of these five GPs. METHODS: A retrospective
      analysis was made of routine mortality and patient registration data from primary
      care practices in West Sussex, and the case notes of deceased patients were
      reviewed. Outcome measures included standardized mortality ratios (SMRs),
      proportion of deaths in nursing homes, and reviewers' concordance with GP
      decisions to issue a death certificate. RESULTS: The high death rates were not
      explained by the age and sex composition of each GP's patient population. SMRs
      ranged from 145 to 239 (average for West Sussex = 100) and all differences from
      the West Sussex average were statistically significant (p <0.02). SMRs were
      highly correlated with the proportion of deaths occurring in nursing homes
      (Pearson's correlation coefficient = 0.95, p = 0.015). Analysis of 153 deceased
      patients' notes revealed no evidence of poor clinical practice. In 114 cases, at
      least one independent reviewer agreed with the decision to issue a death
      certificate. In the remaining 39 (25 per cent) cases, inadequate information in
      the patient's record explained the reviewers' uncertainty about issuing a
      certificate. CONCLUSION: A proportionately high registration of nursing home
      residents is the most likely explanation for the excessive mortality rates of
      these five GPs. This investigation was time-consuming and costly, and highlights
      the potential ramifications for primary-care organizations of introducing a
      national system for monitoring death rates in primary care.

PMID- 16000342
TI  - Massive Trichuris trichiura infection as a cause of chronic bloody diarrhea in a
      child.
AB  - The differential diagnosis of chronic diarrhea is extensive and requires the
      investigation of several diseases, such as celiac disease, inflammatory bowel
      disease and irritable bowel syndrome. A few patients infected by Trichuris
      trichiura may present a chronic dysentery-like syndrome in the context of a
      massive infestation of the colon leading to anemia and growth retardation, but
      the rarity of that finding demands a high level of suspicion. Herein we report
      the case of an 8-year-old boy from the rural zone who had suffered diarrhea
      without blood or mucus for 4 years and was taken to our Service because his
      mother had noticed the presence of blood on the feces on the 3 previous months.
      The diagnosis of a massive Trichuris trichiura infestation as the cause of the
      process was only reached by colonoscopy. We stress that Trichuris trichiura
      infection can mimic other forms of inflammatory bowel disease and lead to
      physical growth retardation and that prolonged regimens of albendazole may be
      required to the effective treatment of massive infestations.

PMID- 16000343
TI  - Carotid intima-media thickness: an index for subclinical atherosclerosis in type
      1 diabetes.
AB  - Cardiovascular disease and the development of coronary artery atherosclerosis
      play a pivotal role in increasing mortality in patients with diabetes. The aim of
      the present study was to determine the presence of subclinical atherosclerosis
      (measured as carotid intima-media thickness [cIMT] and to study possible
      associated risk factors in adolescents with type 1 diabetes. Forty type 1
      diabetic subjects, aged 11-30 years, with duration of diabetes 3-25 years and 40
      normal healthy controls, were included. Blood pressure (BP) measurement, as well
      as screening for diabetic complications, was performed. Lipid profile,
      albumin/creatinine ratio, renal functions and glycosylated hemoglobin (HB A(1)c)
      were assayed. Carotid intima-media thickness (cIMT) was measured using
      ultrasound. The mean aggregate cIMT was higher in diabetics than controls (0.6 mm
      00 +/- 0.1 vs. 0.4 mm +/- 0.1, p = 0.000). Moreover, it was higher in patients
      with positive family history of type 2 diabetes than in those with negative
      family history (mean 0.7 mm +/- 0.1 vs. 0.6 mm +/- 0.1, p = 0.018). cIMT was
      found to positively correlate with: age in both diabetics and controls (r = 0.76,
      p = 0.000, r = 0.74, p = 0.000 respectively), body mass index (BMI) in diabetics
      but not controls (r = 0.82, p = 0.000, r = 0.30, p = 0.06 respectively). In
      diabetics, mean aggregate cIMT positively correlated with duration of diabetes (r
      = 0.66, p = 0.000), systolic blood pressure (r = 0.82, p = 0.000), diastolic BP
      (r = 0.83, p = 0.000), as well as HB A1c (r = 0.40, p = 0.004) and correlated
      negatively with high density lipoprotein -cholesterol (HDL-C) (r = -0.88, p =
      0.000). As cardiovascular morbidity is high in diabetes, non-invasive methods for
      monitoring vascular changes as cIMT might be useful in clinical practice for
      early diagnosis of subclinical atherosclerosis, which can allow for strategies
      designed to reduce the cardiovascular event rate in those patients.

PMID- 16000344
TI  - Evaluation of renal functions in asphyxiated newborns.
AB  - Renal injury due to perinatal asphyxia has not been systematically evaluated. The
      available studies have used variable definitions, incomplete investigations and
      none had a control group. The aim of this study was to evaluate systematically
      the renal functions in severely asphyxiated newborns and to find if abnormal
      renal function tests can predict adverse outcome (death or neurologic abnormality
      at discharge). In a prospective case-control design, 25 inborn babies>or=34 weeks
      gestation having asphyxia (5 min Apgar<or=6 or needing resuscitation>or=5 min)
      were enrolled as 'cases'. Simultaneously 25 gestation and weight matched babies
      with no asphyxia were enrolled as 'controls'. Renal function tests, calculated
      renal indices using timed urine collections and excretion of beta2-microglobulin
      and N-acetyl-beta-D-glucosaminidase (NAG) were monitored in both the groups for
      first 4 days of life. Fourteen (56 per cent) asphyxiated babies had acute renal
      failure (ARF) as compared to 1 (4 per cent) control (p=0.002). Blood urea and
      serum creatinine values were significantly higher in asphyxiated babies on day 4
      but not on day 2. Renal failure index and FeNa were higher in asphyxiated babies
      on both day 2 and day 4, but creatinine clearance was not different. Urinary
      excretion of both beta2-microglobulin and NAG was higher in the asphyxiated
      babies on day 2 as well as day 4. Five minute Apgar<or=6 had the best sensitivity
      to predict renal failure. A combination of high serum creatinine and high blood
      urea had 100 per cent sensitivity and negative predictive value to predict
      adverse outcome while serum creatinine>1.5 mg/dl alone had the best specificity
      and positive predictive value. The renal parameters were however poorer
      predictors of adverse outcome in comparison to clinical markers like 5 min
      Apgar<or=3 and HIE stage II/III. Both glomerular and tubular involvement was seen
      commonly in babies with birth asphyxia. Clinical markers of asphyxia were better
      predictors of adverse outcome than renal function tests.

PMID- 16000345
TI  - Child morbidity and healthcare utilization in the slums of Nairobi, Kenya.
AB  - Rapid urbanization and inequitable distribution of social services in African
      cities significantly contribute to the current deterioration of child health
      indicators in the region. Determinants of child morbidity and healthcare
      utilization among slum residents in Nairobi City, Kenya were assessed. Using a
      morbidity surveillance system, we visited 1691 households every 90 days for 9
      months and registered 696 children below 5 years. 264 (37.9 per cent) children
      were reported to have been sick or injured at least once during the study period.
      A total of 447 illness episodes were reported among the 264 children (an average
      of 1.7 episodes per child). Cough, fever, diarrhea, skin problems and eye
      diseases made up the top five causes of morbidity. Child age below 1 year
      (OR=2.7; 95 per cent CI=1.33, 5.49) and having a working-mother (OR=2.0; 95 per
      cent CI=1.19, 3.31) were significantly associated with child morbidity report.
      About half of the mothers sought proper medical care for their sick children
      mostly from health institutions located outside the slum. Healthcare seeking
      within the slum heavily relied on informal private clinics. Working mothers
      sought medical care more often than non-working mothers (OR=0.29; 95 per cent
      CI=0.12, 0.7) and infants got priorities compared to older sick children (OR=0.2;
      95 per cent CI=0.05, 0.83). We conclude that maternal engagement in non-formal
      low-paying jobs might in the long-run have a questionable gain in child survival
      among slum residents.

PMID- 16000346
TI  - Risk factors for death from meningococcal infection in Recife, Brazil.
AB  - To determine the case fatality rate and risk factors for death in children with
      invasive meningococcal infection, 163 children admitted with meningococcal
      disease to the Instituto Materno Infantil de Pernambuco, a tertiary paediatric
      teaching hospital in Recife, Brazil, were included in this retrospective cohort
      study. Cases were categorised as meningitis, septicaemia and septicaemia with
      meningitis. Forty-six (28.2 per cent) children had meningitis alone, 88 (54 per
      cent) septicaemia and meningitis and 29 (17.8 per cent) only septicaemia. Four of
      the patients with meningitis died (8.7 per cent), compared to 31 out of the 88
      (35.2 per cent) with septicaemia and meningitis and 18 of the 29 (62.1 per cent)
      with septicaemia alone (p < 0.001). Symptoms <24 h (AOR 3.8, 95 per cent CI 1.1
      13.1), platelet count <100 000 mm(3) (AOR 13.8, 95 per cent CI 3.1-60.9) and
      acidosis (AOR 6.0, 95 per cent CI 1.7-21) were the significant risk factors for
      death. Invasive meningococcal infection has a high case-fatality rate in this
      tertiary centre in Recife, especially in the septic forms. The identification of
      risk factors for death could contribute to the early recognition of patients with
      higher risk on admission in a middle-income country population.

PMID- 16000347
TI  - Making antimalarial agents available in the United States.

PMID- 16000348
TI  - Making antimalarial agents available in Africa.

PMID- 16000349
TI  - Images in clinical medicine. Small-bowel prolapse through a persistent
      omphalomesenteric duct.

PMID- 16000350
TI  - Stem-cell research--signposts and roadblocks.

PMID- 16000351
TI  - A role for oxidized phospholipids in atherosclerosis.

PMID- 16000352
TI  - Inhaled nitric oxide for premature infants with severe respiratory failure.
AB  - BACKGROUND: Inhaled nitric oxide is a controversial treatment for premature
      infants with severe respiratory failure. We conducted a multicenter, randomized,
      blinded, controlled trial to determine whether inhaled nitric oxide reduced the
      rate of death or bronchopulmonary dysplasia in such infants. METHODS: We randomly
      assigned 420 neonates, born at less than 34 weeks of gestation, with a birth
      weight of 401 to 1500 g, and with respiratory failure more than four hours after
      treatment with surfactant to receive placebo (simulated flow) or inhaled nitric
      oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure
      of arterial oxygen of more than 10 mm Hg) were weaned according to protocol.
      Treatment with study gas was discontinued in infants who did not have a response.
      RESULTS: The rate of death or bronchopulmonary dysplasia was 80 percent in the
      nitric oxide group, as compared with 82 percent in the placebo group (relative
      risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate
      of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk,
      0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no
      significant differences in the rates of severe intracranial hemorrhage or
      periventricular leukomalacia. Post hoc analyses suggest that rates of death and
      bronchopulmonary dysplasia are reduced for infants with a birth weight greater
      than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled
      nitric oxide have higher mortality and increased rates of severe intracranial
      hemorrhage. CONCLUSIONS: The use of inhaled nitric oxide in critically ill
      premature infants weighing less than 1500 g does not decrease the rates of death
      or bronchopulmonary dysplasia. Further trials are required to determine whether
      inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.

PMID- 16000353
TI  - Neurodevelopmental outcomes of premature infants treated with inhaled nitric
      oxide.
AB  - BACKGROUND: Chronic lung disease and severe intraventricular hemorrhage or
      periventricular leukomalacia in premature infants are associated with abnormal
      neurodevelopmental outcomes. In a previous randomized, controlled, single-center
      trial of premature infants with the respiratory distress syndrome, inhaled nitric
      oxide decreased the risk of death or chronic lung disease as well as severe
      intraventricular hemorrhage and periventricular leukomalacia. We hypothesized
      that infants treated with inhaled nitric oxide would also have improved
      neurodevelopmental outcomes. METHODS: We conducted a prospective, longitudinal
      follow-up study of premature infants who had received inhaled nitric oxide or
      placebo to investigate neurodevelopmental outcomes at two years of corrected age.
      Neurologic examination, neurodevelopmental assessment, and anthropometric
      measurements were made by examiners who were unaware of the children's original
      treatment assignment. RESULTS: A total of 138 children (82 percent of survivors)
      were evaluated. In the group given inhaled nitric oxide, 17 of 70 children (24
      percent) had abnormal neurodevelopmental outcomes, defined as either disability
      (cerebral palsy, bilateral blindness, or bilateral hearing loss) or delay (no
      disability, but one score of less than 70 on the Bayley Scales of Infant
      Development II), as compared with 31 of 68 children (46 percent) in the placebo
      group (relative risk, 0.53; 95 percent confidence interval, 0.33 to 0.87;
      P=0.01). This effect persisted after adjustment for birth weight and sex, as well
      as for the presence or absence of chronic lung disease and severe
      intraventricular hemorrhage or periventricular leukomalacia. The improvement in
      neurodevelopmental outcome in the group given inhaled nitric oxide was primarily
      due to a 47 percent decrease in the risk of cognitive impairment (defined by a
      score of less than 70 on the Bayley Mental Developmental Index) (P=0.03).
      CONCLUSIONS: Premature infants treated with inhaled nitric oxide have improved
      neurodevelopmental outcomes at two years of age.

PMID- 16000354
TI  - Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.
AB  - BACKGROUND: We conducted a randomized comparison of hydroxyurea with anagrelide
      in the treatment of essential thrombocythemia. METHODS: A total of 809 patients
      with essential thrombocythemia who were at high risk for vascular events received
      low-dose aspirin plus either anagrelide or hydroxyurea. The composite primary end
      point was the actuarial risk of arterial thrombosis (myocardial infarction,
      unstable angina, cerebrovascular accident, transient ischemic attack, or
      peripheral arterial thrombosis), venous thrombosis (deep-vein thrombosis,
      splanchnic-vein thrombosis, or pulmonary embolism), serious hemorrhage, or death
      from thrombotic or hemorrhagic causes. RESULTS: After a median follow-up of 39
      months, patients in the anagrelide group were significantly more likely than
      those in the hydroxyurea group to have reached the primary end point (odds ratio,
      1.57; 95 percent confidence interval, 1.04 to 2.37; P=0.03). As compared with
      hydroxyurea plus aspirin, anagrelide plus aspirin was associated with increased
      rates of arterial thrombosis (P=0.004), serious hemorrhage (P=0.008), and
      transformation to myelofibrosis (P=0.01) but with a decreased rate of venous
      thromboembolism (P=0.006). Patients receiving anagrelide were more likely to
      withdraw from their assigned treatment (P<0.001). Equivalent long-term control of
      the platelet count was achieved in both groups. CONCLUSIONS: Hydroxyurea plus low
      dose aspirin is superior to anagrelide plus low-dose aspirin for patients with
      essential thrombocythemia at high risk for vascular events.

PMID- 16000355
TI  - Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease.
AB  - BACKGROUND: Lp(a) lipoprotein binds proinflammatory oxidized phospholipids. We
      investigated whether levels of oxidized low-density lipoprotein (LDL) measured
      with use of monoclonal antibody E06 reflect the presence and extent of
      obstructive coronary artery disease, defined as a stenosis of more than 50
      percent of the luminal diameter. METHODS: Levels of oxidized LDL and Lp(a)
      lipoprotein were measured in a total of 504 patients immediately before coronary
      angiography. Levels of oxidized LDL are reported as the oxidized phospholipid
      content per particle of apolipoprotein B-100 (oxidized phospholipid:apo B-100
      ratio). RESULTS: Measurements of the oxidized phospholipid:apo B-100 ratio and
      Lp(a) lipoprotein levels were skewed toward lower values, and the values for the
      oxidized phospholipid:apo B-100 ratio correlated strongly with those for Lp(a)
      lipoprotein (r=0.83, P<0.001). In the entire cohort, the oxidized
      phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels showed a strong and
      graded association with the presence and extent of coronary artery disease (i.e.,
      the number of vessels with a stenosis of more than 50 percent of the luminal
      diameter) (P<0.001). Among patients 60 years of age or younger, those in the
      highest quartiles for the oxidized phospholipid:apo B-100 ratio and Lp(a)
      lipoprotein levels had odds ratios for coronary artery disease of 3.12 (P<0.001)
      and 3.64 (P<0.001), respectively, as compared with patients in the lowest
      quartile. The combined effect of hypercholesterolemia and being in the highest
      quartiles of the oxidized phospholipid:apo B-100 ratio (odds ratio, 16.8;
      P<0.001) and Lp(a) lipoprotein levels (odds ratio, 14.2; P<0.001) significantly
      increased the probability of coronary artery disease among patients 60 years of
      age or younger. In the entire study group, the association of the oxidized
      phospholipid:apo B-100 ratio with obstructive coronary artery disease was
      independent of all clinical and lipid measures except one, Lp(a) lipoprotein.
      However, among patients 60 years of age or younger, the oxidized phospholipid:apo
      B-100 ratio remained an independent predictor of coronary artery disease.
      CONCLUSIONS: Circulating levels of oxidized LDL are strongly associated with
      angiographically documented coronary artery disease, particularly in patients 60
      years of age or younger. These data suggest that the atherogenicity of Lp(a)
      lipoprotein may be mediated in part by associated proinflammatory oxidized
      phospholipids.

PMID- 16000356
TI  - Potential options for preservation of fertility in women.

PMID- 16000357
TI  - Images in clinical medicine. Ruptured ectopic pregnancy.

PMID- 16000358
TI  - Clinical problem-solving. Double jeopardy.

PMID- 16000359
TI  - Inhaled nitric oxide for preterm infants--who benefits?

PMID- 16000360
TI  - When and how to treat essential thrombocythemia.

PMID- 16000361
TI  - Progress in human somatic-cell nuclear transfer.

PMID- 16000362
TI  - Intensive lipid lowering with atorvastatin in coronary disease.

PMID- 16000363
TI  - A proposal for universal coverage.

PMID- 16000364
TI  - One surprise after another.

PMID- 16000365
TI  - Osteonecrosis of the jaw and bisphosphonates.

PMID- 16000366
TI  - Increased blood vessel density provides the mole rat physiological tolerance to
      its hypoxic subterranean habitat.
AB  - The blind subterranean mole rat superspecies Spalax ehrenbergi has evolved
      adaptations that allow it to survive and carry out intensive activities in its
      highly hypoxic underground sealed burrows. A key component of this adaptation is
      a higher capillary density in some Spalax tissues, primarily in muscles used in
      digging and in other energetic activities, resulting in a shorter diffusion
      distance for oxygen. Vascular endothelial growth factor (VEGF) is an angiogenic
      factor that is critical for angiogenesis during development and is found in
      response to tissue ischemia. We demonstrate here that due to physiological
      differences, the Spalax muscle regulatory mechanism for VEGF is different than in
      Rattus muscle. In vivo, the constitutive level of the VEGF mRNA and the mRNA
      levels of its transcriptional regulator HIF-1alpha and its mRNA stabilizer HuR
      are significantly higher in Spalax muscle than in Rattus muscle. Furthermore, as
      opposed to Rattus, the mRNA levels of HIF-1alpha, HuR, VEGF, as well as that of
      LDH-A, the enzyme that catalyzes the production of lactate, an accepted marker of
      anaerobic metabolism, are not increased in Spalax after hypoxia. However, ex
      vivo, when oxygenation by blood vessels is no longer relevant, the expression
      pattern of all these genes is similar in the two rodents under both normoxic and
      hypoxic conditions. Our studies provide evidence that the highly vascularized
      muscle in Spalax, the most energy consuming tissue during digging, is resistant
      to the effects of oxygen deprivation. The significance of these results with
      respect to ischemic vascular disease is abundantly clear.

PMID- 16000367
TI  - Illuminating cases: understanding the economic burden of illness through case
      study household research.
AB  - Understanding the economic burden of illness for households can inform pro-poor
      health and social protection policy, yet research is in its infancy and
      appropriate methods require further debate. Quantitative studies are powerful
      when applied to the right health policy questions, including the measurement of
      illness cost burden indicators. However, this paper argues that not all
      dimensions of economic burden can be measured easily, some dimensions relevant to
      policy, such as social actors' responses to illness and their strategies to cope
      with illness costs, cannot be reduced to quantitative indicators at all, and
      large-scale surveys may overlook context-specific processes operating at
      household level that influence people's paths in and out of poverty as a result
      of illness. This leaves scope for longitudinal case-study household research to
      enhance understanding of economic burden and provide additional policy insights
      on how to better protect households from cost burdens and improve resilience.
      Drawing on the experience of research in urban Sri Lanka, the paper sets out
      several comparative advantages of case study research in this area. First, it
      complemented household survey data by revealing the complex and dynamic nature of
      illness costs and how these cost patterns (for example, sudden cost peaks)
      influenced household ability to manage costs. Secondly, it improved understanding
      of vulnerability or resilience to illness costs by capturing the diverse
      resources, within and outside the household, used by people to cope with illness
      costs, and the social institutions and decision-making processes that influenced
      access to them. Thirdly, the cases enabled the research to develop a picture of
      the inter-connected factors mediating the impact of illness on livelihood
      outcomes.

PMID- 16000368
TI  - Implementing global knowledge in local practice: a WHO lung health initiative in
      Nepal.
AB  - Clinical practice guidelines are used widely to improve the quality of primary
      health care in different health systems, including those of low-income countries.
      Often developed at international level and adapted to national contexts to
      increase the feasibility of effective uptake, guideline initiatives aim to
      transfer global scientific knowledge into local practice. The WHO's Practical
      Approach to Lung Health (PAL) is an example of such an initiative and is
      currently being developed to improve the quality of care for youths and adults
      with respiratory diseases. We assessed ex-ante the feasibility of successful
      implementation of PAL in a pilot programme in rural Nepal, studying three
      components: the quality of the innovation (i.e. the guidelines), the
      effectiveness of the implementation strategy (i.e. training) and the
      receptiveness of the social system of health staff at all levels (i.e. social and
      organizational characteristics). We assessed the guideline innovation with the
      AGREE instrument for guidelines, the intended implementation strategy by critical
      comparison with literature on effective strategies, and the social system with
      both a stakeholder analysis and a descriptive analysis of the health care system
      at district level. This ex-ante assessment of an adaptive local implementation of
      international WHO guidelines showed that in July 2002 the 'implementability' of
      the package was challenged on the three components studied. To increase the
      chances of successful implementation, the national guideline development process
      should be improved and the implementation strategy needs to be upgraded. In order
      to successfully transfer global knowledge into local practice, we need to develop
      additional multifactorial sustained interventions that tackle other culture
      specific and health system-specific barriers as well. The primary health workers
      are key informants for these barriers.

PMID- 16000369
TI  - Antibiotic use following a Korean national policy to prohibit medication
      dispensing by physicians.
AB  - This study investigated whether a Korean national policy prohibiting doctors from
      dispensing drugs as of 2000 selectively reduced inappropriate antibiotic
      prescribing in viral illness compared with bacterial illness. We assessed the
      proportions of episodes prescribed an antibiotic and the number of different
      antibiotics prescribed for patients with viral and bacterial illness episodes
      before and after the policy. The nationally representative sample consisted of
      50,999 episodes (18,656 viral and 7758 bacterial pre-policy, 16,736 viral and
      7849 bacterial post-policy) from 1372 primary care clinics. We used generalized
      estimating equations to investigate changes in antibiotic prescribing after the
      policy, and multiple linear regression to determine provider factors associated
      with reductions in inappropriate antibiotic prescribing for viral illness. After
      the dispensing restriction, antibiotic prescribing declined substantially for
      patients with viral illness (from 80.8 to 72.8%, relative risk (RR) = 0.89, [95%
      confidence interval: 0.86, 0.91], p<0.001), and only minimally for patients with
      bacterial illness (from 91.6 to 89.7%, RR = 0.98, [0.97, 0.99], p = 0.017).
      Reductions in antibiotic prescribing were significantly larger (RR = 0.90, [0.87,
      0.93], p<0.001) for patients with viral illness. The number of different
      antibiotics prescribed per episode also decreased significantly after the policy,
      but there were no significant differences in these reductions between viral and
      bacterial illness. The dispensing restriction also reduced prescribing of non
      antibiotic drugs, with no difference by diagnosis. Provider factors found to be
      associated with reduced inappropriate antibiotic prescribing were younger age and
      practice location in an urban area. Prohibiting doctors from dispensing drugs
      reduced prescribing overall, both of antibiotics and other drugs, and selectively
      reduced inappropriate antibiotic prescribing in viral illness.

PMID- 16000370
TI  - Sprouty-2 overexpression in C2C12 cells confers myogenic differentiation
      properties in the presence of FGF2.
AB  - Myoblast C2C12 cells cultured in the presence of FGF2 actively proliferate and
      showed a differentiation-defective phenotype compared with cells cultured in low
      serum or in the presence of insulin. These FGF2 effects are associated with
      sustained activation of p44/p42-MAPK and lack of activation of AKT. Here we
      demonstrate that Sprouty-2, a protein involved in the negative feedback of
      receptor tyrosine kinase signaling, when stably overexpressed in C2C12 cells and
      in the presence of FGF2 produces growth arrest (precluding the expression of PCNA
      and the phosphorylation of retinoblastoma and inducing the expression of
      p21(CIP)) and myogenesis (multinucleated myotubes formation, induction of
      creatine kinase and expression of myosin heavy chain protein). These events were
      accompanied by repression of p44/p42-MAPK and activation of AKT. When C2C12 cells
      were stably transfected with a Sprouty-2 (Y55F) mutant defective in inhibiting
      p44/p42-MAPK activation by FGF, myoblasts in the presence of FGF continue to grow
      and completely fail to form myotubes. This work is the first evidence of the
      contribution of sprouty genes to myogenic differentiation in the presence of
      FGF2.

PMID- 16000371
TI  - The RNA-binding protein fragile X-related 1 regulates somite formation in Xenopus
      laevis.
AB  - Fragile X-related 1 protein (FXR1P) is a member of a small family of RNA-binding
      proteins that includes the Fragile X mental retardation 1 protein (FMR1P) and the
      Fragile X-related 2 protein (FXR2P). These proteins are thought to transport mRNA
      and to control their translation. While FMR1P is highly expressed in neurons,
      substantial levels of FXR1P are found in striated muscles and heart, which are
      devoid of FMRP and FXR2P. However, little is known about the functions of FXR1P.
      We have isolated cDNAs for Xenopus Fxr1 and found that two specific splice
      variants are conserved in evolution. Knockdown of xFxr1p in Xenopus had highly
      muscle-specific effects, normal MyoD expression being disrupted, somitic myotomal
      cell rotation and segmentation being inhibited, and dermatome formation being
      abnormal. Consistent with the absence of the long muscle-specific xFxr1p isoform
      during early somite formation, these effects could be rescued by both the long
      and short mRNA variants. Microarray analyses showed that xFxr1p depletion
      affected the expression of 129 known genes of which 50% were implicated in muscle
      and nervous system formation. These studies shed significant new light on Fxr1p
      function(s).

PMID- 16000372
TI  - Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1)
      demonstrates that TgAMA1 plays a critical role in host cell invasion.
AB  - Toxoplasma gondii is an obligate intracellular parasite and an important human
      pathogen. Relatively little is known about the proteins that orchestrate host
      cell invasion by T. gondii or related apicomplexan parasites (including
      Plasmodium spp., which cause malaria), due to the difficulty of studying
      essential genes in these organisms. We have used a recently developed regulatable
      promoter to create a conditional knockout of T. gondii apical membrane antigen-1
      (TgAMA1). TgAMA1 is a transmembrane protein that localizes to the parasite's
      micronemes, secretory organelles that discharge during invasion. AMA1 proteins
      are conserved among apicomplexan parasites and are of intense interest as malaria
      vaccine candidates. We show here that T. gondii tachyzoites depleted of TgAMA1
      are severely compromised in their ability to invade host cells, providing direct
      genetic evidence that AMA1 functions during invasion. The TgAMA1 deficiency has
      no effect on microneme secretion or initial attachment of the parasite to the
      host cell, but it does inhibit secretion of the rhoptries, organelles whose
      discharge is coupled to active host cell penetration. The data suggest a model in
      which attachment of the parasite to the host cell occurs in two distinct stages,
      the second of which requires TgAMA1 and is involved in regulating rhoptry
      secretion.

PMID- 16000373
TI  - Cell adhesion strengthening: contributions of adhesive area, integrin binding,
      and focal adhesion assembly.
AB  - Mechanical interactions between a cell and its environment regulate migration,
      contractility, gene expression, and cell fate. We integrated micropatterned
      substrates to engineer adhesive area and a hydrodynamic assay to analyze
      fibroblast adhesion strengthening on fibronectin. Independently of cell
      spreading, integrin binding and focal adhesion assembly resulted in rapid
      sevenfold increases in adhesion strength to steady-state levels. Adhesive area
      strongly modulated adhesion strength, integrin binding, and vinculin and talin
      recruitment, exhibiting linear increases for small areas. However, above a
      threshold area, adhesion strength and focal adhesion assembly reached a
      saturation limit, whereas integrin binding transitioned from a uniform
      distribution to discrete complexes. Adhesion strength exhibited exponential
      increases with bound integrin numbers as well as vinculin and talin recruitment,
      and the relationship between adhesion strength and these biochemical events was
      accurately described by a simple mechanical model. Furthermore, adhesion strength
      was regulated by the position of an adhesive patch, comprised of bound integrins
      and cytoskeletal elements, which generated a constant 200-nN adhesive force.
      Unexpectedly, focal adhesion assembly, in particular vinculin recruitment,
      contributed only 30% of the adhesion strength. This work elucidates the roles of
      adhesive complex size and position in the generation of cell-extracellular matrix
      forces.

PMID- 16000374
TI  - Stochastic simulation of neurofilament transport in axons: the "stop-and-go"
      hypothesis.
AB  - According to the "stop-and-go" hypothesis of slow axonal transport, cytoskeletal
      and cytosolic proteins are transported along axons at fast rates but the average
      velocity is slow because the movements are infrequent and bidirectional. To test
      whether this hypothesis can explain the kinetics of slow axonal transport in
      vivo, we have developed a stochastic model of neurofilament transport in axons.
      We propose that neurofilaments move in both anterograde and retrograde directions
      along cytoskeletal tracks, alternating between short bouts of rapid movement and
      short "on-track" pauses, and that they can also temporarily disengage from these
      tracks, resulting in more prolonged "off-track" pauses. We derive the kinetic
      parameters of the model from a detailed analysis of the moving and pausing
      behavior of single neurofilaments in axons of cultured neurons. We show that the
      model can match the shape, velocity, and spreading of the neurofilament transport
      waves obtained by radioisotopic pulse labeling in vivo. The model predicts that
      axonal neurofilaments spend approximately 8% of their time on track and
      approximately 97% of their time pausing during their journey along the axon.

PMID- 16000375
TI  - Src and FAK kinases cooperate to phosphorylate paxillin kinase linker, stimulate
      its focal adhesion localization, and regulate cell spreading and protrusiveness.
AB  - The ArfGAP paxillin kinase linker (PKL)/G protein-coupled receptor kinase
      interacting protein (GIT)2 has been implicated in regulating cell spreading and
      motility through its transient recruitment of the p21-activated kinase (PAK) to
      focal adhesions. The Nck-PAK-PIX-PKL protein complex is recruited to focal
      adhesions by paxillin upon integrin engagement and Rac activation. In this
      report, we identify tyrosine-phosphorylated PKL as a protein that associates with
      the SH3-SH2 adaptor Nck, in a Src-dependent manner, after cell adhesion to
      fibronectin. Both cell adhesion and Rac activation stimulated PKL tyrosine
      phosphorylation. PKL is phosphorylated on tyrosine residues 286/392/592 by Src
      and/or FAK and these sites are required for PKL localization to focal adhesions
      and for paxillin binding. The absence of either FAK or Src-family kinases
      prevents PKL phosphorylation and suppresses localization of PKL but not GIT1 to
      focal adhesions after Rac activation. Expression of an activated FAK mutant in
      the absence of Src-family kinases partially restores PKL localization, suggesting
      that Src activation of FAK is required for PKL phosphorylation and localization.
      Overexpression of the nonphosphorylated GFP-PKL Triple YF mutant stimulates cell
      spreading and protrusiveness, similar to overexpression of a paxillin mutant that
      does not bind PKL, suggesting that failure to recruit PKL to focal adhesions
      interferes with normal cell spreading and motility.

PMID- 16000376
TI  - Specific interaction of the actin-binding domain of dystrophin with intermediate
      filaments containing keratin 19.
AB  - Cytokeratins 8 and 19 concentrate at costameres of striated muscle and copurify
      with the dystrophin-glycoprotein complex, perhaps through the interaction of the
      cytokeratins with the actin-binding domain of dystrophin. We overexpressed
      dystrophin's actin-binding domain (Dys-ABD), K8 and K19, as well as closely
      related proteins, in COS-7 cells to assess the basis and specificity of their
      interaction. Dys-ABD alone associated with actin microfilaments. Expressed with
      K8 and K19, which form filaments, Dys-ABD associated preferentially with the
      cytokeratins. This interaction was specific, as the homologous ABD of betaI
      spectrin failed to interact with K8/K19 filaments, and Dys-ABD did not associate
      with desmin or K8/K18 filaments. Studies in COS-7 cells and in vitro showed that
      Dys-ABD binds directly and specifically to K19. Expressed in muscle fibers in
      vivo, K19 accumulated in the myoplasm in structures that contained dystrophin and
      spectrin and disrupted the organization of the sarcolemma. K8 incorporated into
      sarcomeres, with no effect on the sarcolemma. Our results show that dystrophin
      interacts through its ABD with K19 specifically and are consistent with the idea
      that cytokeratins associate with dystrophin at the sarcolemma of striated muscle.

PMID- 16000377
TI  - Interactions between Mad1p and the nuclear transport machinery in the yeast
      Saccharomyces cerevisiae.
AB  - In addition to its role in nucleocytoplasmic transport, the nuclear pore complex
      (NPC) acts as a docking site for proteins whose apparent primary cellular
      functions are unrelated to nuclear transport, including Mad1p and Mad2p, two
      proteins of the spindle assembly checkpoint (SAC) machinery. To understand this
      relationship, we have mapped domains of yeast Saccharomyces cerevisiae Mad1p that
      interact with the nuclear transport machinery, including further defining its
      interactions with the NPC. We showed that a Kap95p/Kap60p-dependent nuclear
      localization signal, positioned in the C-terminal third of Mad1p, is required for
      its efficient targeting to the NPC. At the NPC, Mad1p interacts with Nup53p and a
      presumed Nup60p/Mlp1p/Mlp2p complex through two coiled coil regions within its N
      terminus. When the SAC is activated, a portion of Mad1p is recruited to
      kinetochores through an interaction that is mediated by the C-terminal region of
      Mad1p and requires energy. We showed using photobleaching analysis that in
      nocodazole-arrested cells Mad1p rapidly cycles between the Mlp proteins and
      kinetochores. Our further analysis also showed that only the C terminus of Mad1p
      is required for SAC function and that the NPC, through Nup53p, may act to
      regulate the duration of the SAC response.

PMID- 16000378
TI  - Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis
      and is abrogated by alpha B-crystallin through inhibition of RAS activation.
AB  - The ocular lens is the only organ that does not develop spontaneous tumor. The
      molecular mechanism for this phenomenon remains unknown. Through examination of
      the signaling pathways mediating stress-induced apoptosis, here we presented
      evidence to show that different from most other tissues in which the
      extracellular signal-regulated kinases (ERKs) pathway is generally implicated in
      mediation of survival signals activated by different factors, the RAF/MEK/ERK
      signaling pathway alone plays a key role in stress-activated apoptosis of lens
      epithelial cells. Treatment of N/N1003A cells with calcimycin, a calcium
      mobilizer, activates the RAF/MEK/ERK pathway through RAS, which is indispensable
      for the induced apoptosis because inhibition of this pathway by either
      pharmacological drug or dominant negative mutants greatly attenuates the induced
      apoptosis. Calcimycin also activates p38 kinase and JNK2, which are not involved
      in calcium-induced apoptosis. Downstream of ERK activation, p53 is essential.
      Activation of RAF/MEK/ERK pathway by calcimycin leads to distinct up-regulation
      of p53. Moreover, overexpression of p53 enhances calcimycin-induced apoptosis,
      whereas inhibition of p53 expression attenuates calcimycin-induced apoptosis. Up
      regulation of p53 directly promotes Bax expression, which changes the integrity
      of mitochondria, leading to release of cytochrome c, activation of caspase-3 and
      eventually execution of apoptosis. Overexpression of alphaB-crystallin, a member
      of the small heat-shock protein family, blocks activation of RAS to inhibit
      ERK1/2 activation, and greatly attenuates calcimycin-induced apoptosis. Together,
      our results provide 1) a partial explanation for the lack of spontaneous tumor in
      the lens, 2) a novel signaling pathway for calcium-induced apoptosis, and 3) a
      novel antiapoptotic mechanism for alphaB-crystallin.

PMID- 16000380
TI  - C-terminal mutants of C. elegans Smads reveal tissue-specific requirements for
      protein activation by TGF-beta signaling.
AB  - TGF-beta signaling in the nematode Caenorhabditis elegans plays multiple roles in
      the development of the animal. The Sma/Mab pathway controls body size, male tail
      sensory ray identity and spicule formation. Three Smad genes, sma-2, sma-3 and
      sma-4, are all required for signal transduction, suggesting that the functional
      complex could be a heterotrimer. Because the C termini of Smads play important
      roles in receptor-mediated activation and heteromeric complex formation, we
      generated C-terminal mutations in the C. elegans Smad genes and tested their
      activities in vivo in each of their distinct developmental roles. We show that
      pseudophosphorylated SMA-3 is dominant negative in body size, but functional in
      sensory ray and spicule development. Somewhat differently, pseudophosphorylated
      SMA-2 is active in any tissue. The C-terminal mutants of SMA-4 function like wild
      type, suggesting that the SMA-4 C terminus is dispensable. Using a combination of
      different C-terminal mutations in SMA-2 and SMA-3, we found a complex set of
      requirements for Smad-phosphorylation state that are specific to each outcome.
      Finally, we detected a physical interaction of SMA-3 with the forkhead
      transcription factor LIN-31, which is enhanced by SMA-3 pseudophosphorylation and
      reduced in an unphosphorylatable mutant. We conclude that the tissue-specific
      requirements for Smad phosphorylation may result, in part, from the need to
      interact with tissue-specific transcription co-factors that have different
      affinities for phosphorylated and unphosphorylated Smad protein.

PMID- 16000379
TI  - Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin
      hCG1: a conserved mechanism in the export of Hsp70 mRNA.
AB  - Translocation of messenger RNAs through the nuclear pore complex (NPC) requires
      coordinated physical interactions between stable NPC components, shuttling
      transport factors, and mRNA-binding proteins. In budding yeast (y) and human (h)
      cells, Gle1 is an essential mRNA export factor. Nucleocytoplasmic shuttling of
      hGle1 is required for mRNA export; however, the mechanism by which hGle1
      associates with the NPC is unknown. We have previously shown that the interaction
      of hGle1 with the nucleoporin hNup155 is necessary but not sufficient for
      targeting hGle1 to NPCs. Here, we report that the unique C-terminal 43 amino acid
      region of the hGle1B isoform mediates binding to the C-terminal non-FG region of
      the nucleoporin hCG1/NPL1. Moreover, hNup155, hGle1B, and hCG1 formed a
      heterotrimeric complex in vitro. This suggested that these two nucleoporins were
      required for the NPC localization of hGle1. Using an siRNA-based approach,
      decreased levels of hCG1 resulted in hGle1 accumulation in cytoplasmic foci. This
      was coincident with inhibition of heat shock-induced production of Hsp70 protein
      and export of the Hsp70 mRNA in HeLa cells. Because this closely parallels the
      role of the hCG1 orthologue yNup42/Rip1, we speculate that hGle1-hCG1 function in
      the mRNA export mechanism is highly conserved.

PMID- 16000381
TI  - Tec29 controls actin remodeling and endoreplication during invagination of the
      Drosophila embryonic salivary glands.
AB  - Epithelial invagination is necessary for formation of many tubular organs, one of
      which is the Drosophila embryonic salivary gland. We show that actin
      reorganization and control of endocycle entry are crucial for normal invagination
      of the salivary placodes. Embryos mutant for Tec29, the Drosophila Tec family
      tyrosine kinase, showed delayed invagination of the salivary placodes. This
      invagination delay was partly the result of an accumulation of G-actin in the
      salivary placodes, indicating that Tec29 is necessary for maintaining the
      equilibrium between G- and F-actin during invagination of the salivary placodes.
      Furthermore, normal invagination of the salivary placodes appears to require the
      proper timing of the endocycle in these cells; Tec29 must delay DNA
      endoreplication in the salivary placode cells until they have invaginated into
      the embryo. Taken together, these results show that Tec29 regulates both the
      actin cytoskeleton and the cell cycle to facilitate the morphogenesis of the
      embryonic salivary glands. We suggest that apical constriction of the actin
      cytoskeleton may provide a temporal cue ensuring that endoreplication does not
      begin until the cells have finished invagination.

PMID- 16000382
TI  - Mind bomb 1 is essential for generating functional Notch ligands to activate
      Notch.
AB  - The Delta-Notch signaling pathway is an evolutionarily conserved intercellular
      signaling mechanism essential for cell fate specification. Mind bomb 1 (Mib1) has
      been identified as a ubiquitin ligase that promotes the endocytosis of Delta. We
      now report that mice lacking Mib1 die prior to embryonic day 11.5, with pan-Notch
      defects in somitogenesis, neurogenesis, vasculogenesis and cardiogenesis. The
      Mib1-/- embryos exhibit reduced expression of Notch target genes Hes5, Hey1, Hey2
      and Heyl, with the loss of N1icd generation. Interestingly, in the Mib1-/-
      mutants, Dll1 accumulated in the plasma membrane, while it was localized in the
      cytoplasm near the nucleus in the wild types, indicating that Mib1 is essential
      for the endocytosis of Notch ligand. In accordance with the pan-Notch defects in
      Mib1-/- embryos, Mib1 interacts with and regulates all of the Notch ligands,
      jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. Our results show that Mib1
      is an essential regulator, but not a potentiator, for generating functional Notch
      ligands to activate Notch signaling.

PMID- 16000384
TI  - Potential structural role of non-coding and coding RNAs in the organization of
      the cytoskeleton at the vegetal cortex of Xenopus oocytes.
AB  - The localization of RNA within a cell or embryo is crucial for proper cellular
      function or development. There is evidence that the cytoskeleton and RNA may
      function in the anchoring of localized RNAs at the vegetal cortex of Xenopus
      laevis oocytes. We found that the organization of the cytokeratin filaments but
      not the actin cytoskeleton depends on the presence of intact VegT mRNA and a
      noncoding RNA, Xlsirts. Destruction of either of these transcripts results in
      disruption of the cytokeratin cytoskeleton in a transcript-specific manner and
      interferes with proper formation of the germinal granules and subsequent
      development of the germline. Analysis of the distribution of endogenous VegT and
      Xlsirts in live oocytes using molecular beacons showed that these RNAs are
      integrated into the cytokeratin cytoskeleton. These results demonstrate a novel
      structural role of coding and noncoding RNAs in the organization of the vegetal
      cortex of Xenopus oocytes.

PMID- 16000383
TI  - Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB.
AB  - RNA-binding proteins control germline development in metazoans. This work focuses
      on control of the C. elegans germline by two RNA-binding proteins: FOG-1, a CPEB
      homolog; and FBF, a PUF family member. Previous studies have shown that FOG-1
      specifies the sperm fate and that FBF promotes proliferation. Here, we report
      that FOG-1 also promotes proliferation. Whereas fbf-1 fbf-2 double mutants make
      approximately 120 germ cells, fog-1; fbf-1 fbf-2 triple mutants make only
      approximately 10 germ cells. The triple mutant germline divides normally until
      early L2, when germ cells prematurely enter meiosis and begin oogenesis.
      Importantly, fog-1/+; fbf-1 fbf-2 animals make more germ cells than fbf-1 fbf-2
      double mutants, demonstrating that one dose of wild-type fog-1 promotes
      proliferation more effectively than two doses - at least in the absence of FBF.
      FOG-1 protein is barely detectable in proliferating germ cells, but abundant in
      germ cells destined for spermatogenesis. Based on fog-1 dose effects, together
      with the gradient of FOG-1 protein abundance, we suggest that low FOG-1 promotes
      proliferation and high FOG-1 specifies spermatogenesis. FBF binds specifically to
      regulatory elements in the fog-1 3'UTR, and FOG-1 increases in animals lacking
      FBF. Therefore, FBF represses fog-1 expression. We suggest that FBF promotes
      continued proliferation, at least in part, by maintaining FOG-1 at a low level
      appropriate for proliferation. The dose-dependent control of proliferation and
      cell fate by FOG-1 has striking parallels with Xenopus CPEB, suggesting a
      conserved mechanism in animal development.

PMID- 16000385
TI  - A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as
      models of liver disease.
AB  - Hepatomegaly is a sign of many liver disorders. To identify zebrafish mutants to
      serve as models for hepatic pathologies, we screened for hepatomegaly at day 5 of
      embryogenesis in 297 zebrafish lines bearing mutations in genes that are
      essential for embryonic development. Seven mutants were identified, and three
      have phenotypes resembling different liver diseases. Mutation of the class C
      vacuolar protein sorting gene vps18 results in hepatomegaly associated with
      large, vesicle-filled hepatocytes, which we attribute to the failure of endosomal
      lysosomal trafficking. Additionally, these mutants develop defects in the bile
      canaliculi and have marked biliary paucity, suggesting that vps18 also functions
      to traffic vesicles to the hepatocyte apical membrane and may play a role in the
      development of the intrahepatic biliary tree. Similar findings have been reported
      for individuals with arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome,
      which is due to mutation of another class C vps gene. A second mutant, resulting
      from disruption of the tumor suppressor gene nf2, develops extrahepatic
      choledochal cysts in the common bile duct, suggesting that this gene regulates
      division of biliary cells during development and that nf2 may play a role in the
      hyperplastic tendencies observed in biliary cells in individuals with choledochal
      cysts. The third mutant is in the novel gene foie gras, which develops large,
      lipid-filled hepatocytes, resembling those in individuals with fatty liver
      disease. These mutants illustrate the utility of zebrafish as a model for
      studying liver development and disease, and provide valuable tools for
      investigating the molecular pathogenesis of congenital biliary disorders and
      fatty liver disease.

PMID- 16000386
TI  - Requirement for JAK/STAT signaling throughout border cell migration in
      Drosophila.
AB  - The evolutionarily conserved JAK/STAT signaling pathway is essential for the
      proliferation, survival and differentiation of many cells including cancer cells.
      Recent studies have implicated this transcriptional pathway in the process of
      cell migration in humans, mice, Drosophila and Dictyostelium. In the Drosophila
      ovary, JAK/STAT signaling is necessary and sufficient for the specification and
      migration of a group of cells called the border cells; however, it is not clear
      to what extent the requirement for cell fate is distinct from that for cell
      migration. We found that STAT protein is enriched in the migrating border cells
      throughout their migration and is an indicator of cells with highest JAK/STAT
      activity. In addition, stat(ts) mutants exhibited border cell migration defects
      after just 30 minutes at the non-permissive temperature, prior to any detectable
      change in the expression of cell fate markers. At later times, cell fate changes
      became evident, indicating that border cell fate is labile. JAK/STAT signaling
      was also required for organization of the border cell cluster. Finally, we show
      that both the accumulation of STAT protein and nuclear accumulation are
      positively regulated by JAK/STAT activity. The activity of the pathway is
      negatively regulated by overexpression of a SOCS protein and by blocking
      endocytosis. Together, our findings suggest that the requirement for STAT in
      border cells extends beyond the initial specification and delamination of cells
      from the epithelium.

PMID- 16000387
TI  - Negative regulatory role of mannose receptors on human alveolar macrophage
      proinflammatory cytokine release in vitro.
AB  - Alveolar macrophages (AM) are critical components of lung innate immunity and
      contribute to an effective host response to Pneumocystis pneumonia. Recognition
      of unopsonized Pneumocystis organisms by human AM is mediated predominantly via
      mannose receptors and results in phagocytosis, release of reactive oxygen
      species, and activation of the nuclear transcription factor (NF)-kappaB. However,
      the AM host defense genes activated by Pneumocystis have not been defined. In the
      present study, incubation of AM with unopsonized Pneumocystis organisms was not
      associated with release of interleukin (IL)-1beta, IL-6, or tumor necrosis factor
      (TNF)-alpha (important cytokines in the host response to Pneumocystis) and did
      not induce IL-1beta, IL-6, or TNF-alpha mRNA transcripts. These findings were not
      attributed to Pneumocystis-induced cytopathic changes, as these same AM released
      IL-8 and matrix metalloproteinase-9 in response to Pneumocystis. NF-kappaB
      mediated IL-8 release was independent of Pneumocystis phagocytosis. The observed
      response was specific, as IL-1beta, IL-6, and TNF-alpha release and mRNA
      induction were preserved in response to lipopolysaccharide or serum-opsonized
      Pneumocystis. The absence of IL-1beta, IL-6, and TNF-alpha release in response to
      Pneumocystis was predominately influenced by AM mannose receptors, as blocking
      mannose receptors or targeted mannose receptor small interfering RNA functional
      gene silencing resulted in TNF-alpha release in response to unopsonized
      Pneumocystis organisms. Furthermore, ligation of AM mannose receptors by
      unopsonized Pneumocystis organisms reduced Toll-like receptor 4-mediated TNF
      alpha release. Taken together, these data suggest that mannose receptors on human
      AM may suppress select proinflammatory cytokine release and may serve to regulate
      the innate inflammatory responses to infectious challenge in the lungs.

PMID- 16000388
TI  - Effect of antithrombin III on neutrophil deformability.
AB  - As the spherical diameter of pulmonary capillaries is smaller than that of
      neutrophils, increased neutrophil stiffness or conversely, decreased neutrophil
      deformability is a key step in the initial sequestration of neutrophils within
      the lungs during inflammatory processes. Antithrombin III (AT) is known to exert
      a therapeutic effect against disseminated intravascular coagulation, and
      accumulating evidence suggests that AT also has anti-inflammatory properties. The
      mechanisms of its anti-inflammatory effects remain unclear, but in a rat
      endotoxin model, AT apparently inhibited neutrophil sequestration in the lung. In
      the present in vitro study, therefore, we examined the effect of AT on the
      deformability of human neutrophils and correlated those findings with their F
      actin content. Isolated human neutrophils were stimulated with formyl-Met-Leu-Phe
      (1 muM, 2 min) in the presence or absence of the alpha, beta, or low heparin
      affinity isoforms of AT (1 IU/ml, 20 min), and deformability was evaluated using
      a filter assay system. Neutrophils were also stained with fluorescein
      isothiocyanate-phalloidin and subjected to a fluorescein-activated cell sorter
      scan to assess F-actin content. The results showed that pretreatment with any of
      the three AT isoforms similarly inhibited the decreased neutrophil deformability
      and increased F-actin content of stimulated cells. Notably, heparinase had no
      effect on deformability or F-actin content in the presence or absence of AT,
      which was somewhat unexpected, as heparin sulfate proteoglycans likely function
      as AT receptors. These findings suggested that AT inhibits the increase in
      neutrophil stiffness seen during inflammatory processes by inhibiting actin
      polymerization via a heparin-independent pathway.

PMID- 16000389
TI  - Human peripheral blood monocytes express protease receptor-2 and respond to
      receptor activation by production of IL-6, IL-8, and IL-1{beta}.
AB  - Protease-activated receptor-2 (PAR-2) belongs to a family of G-coupled receptors
      activated by proteolytic cleavage to reveal a tethered ligand. PAR-2 is activated
      by trypsin and trypsin-like serine proteases and experimentally, by receptor
      activating peptides (APs), which mimic the tethered ligand. PAR-2 has recently
      been implicated in proinflammatory immune responses. For example, PAR-2(-/-) mice
      exhibit markedly diminished contact hypersensitivity reactions and are completely
      resistant to adjuvant-induced arthritis. The present study shows that human blood
      monocytes express low-level cell-surface PAR-2 ex vivo, which is up-regulated
      upon cell purification by the mobilization of intracellular stores of PAR-2
      protein. PAR-2 expression is also present on monocyte-derived macrophages, but
      only a small proportion of monocyte-derived dendritic cells (DC) is PAR-2(+), and
      blood DC are PAR(-). Freshly isolated monocytes responded to the PAR-2 AP ASKH 95
      (2-furoyl-LIGKV-OH) with the generation of a calcium flux and production of
      interleukin (IL)-1beta, IL-6, and IL-8. The results presented thus suggest that
      PAR-2 contributes to inflammatory responses by inducing the production of
      proinflammatory cytokines in peripheral blood monocytes.

PMID- 16000390
TI  - HLA-A2 down-regulation on primary human macrophages infected with an M-tropic
      EGFP-tagged HIV-1 reporter virus.
AB  - Multiple mechanisms are used by the human immunodeficiency virus type 1 (HIV-1)
      to interfere with host-cell immune effector functions. The 27-kD Nef protein has
      been shown to down-modulate specific genes of the major histocompatibility
      complex class I (MHC-I) on the surface of infected primary T cells, facilitating
      their escape from lysis by cytolytic T lymphocytes. Macrophages, as the other
      major immune cell type targeted by the virus, also contribute to the
      transmission, persistence, and pathogenesis of HIV-1. Yet, whether Nef modulates
      MHC-I expression on HIV-infected primary macrophages remains unclear. Currently
      available infectious HIV-1 molecular clones, which express a reporter gene, only
      infect T cells and/or do not express Nef. To overcome these limitations, we
      generated macrophage-tropic green fluorescent protein (GFP)-tagged HIV-1 viruses,
      which express the complete viral genome, and used these to assess the expression
      of human leukocyte antigen (HLA)-A2 on the surface of productively infected
      macrophages. The reporter viral genomes were replication-competent and stable, as
      Nef, p24 antigen, and GFP expression could be detected by immunostaining of
      infected, monocyte-derived macrophages (MDM) after more than 2 months
      postinfection. Fluorescence-activated cell sorter analyses of infected
      macrophages and T cells revealed that although wild-type reporter virus infection
      induced a statistically significant decrease in the density of surface HLA-A2,
      down-regulation of HLA-A2 was not seen in cells infected with reporter viruses
      encoding a frameshift or a single point mutation in Nef at prolines 74P and P80.
      The impact of Nef on HLA-A2 surface expression in MDM was also confirmed by
      confocal microscopy. These results suggest that the mechanisms of HLA-A2 down
      modulation are similar in primary T cells and macrophages.

PMID- 16000391
TI  - Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo and
      increased responsiveness in vitro.
AB  - The role of the endogenous anti-inflammatory mediator annexin 1 (AnxA1) in
      controlling polymorphonuclear leukocyte (PMN) trafficking and activation was
      addressed using the recently generated AnxA1 null mouse. In the zymosan
      peritonitis model, AnxA1 null mice displayed a higher degree (50-70%) of PMN
      recruitment compared with wild-type littermate mice, and this was associated with
      reduced numbers of F4/80+ cells. Intravital microscopy analysis of the cremaster
      microcirculation inflamed by zymosan (6 h time-point) indicated a greater extent
      of leukocyte emigration, but not rolling or adhesion, in AnxA1 null mice. Real
      time analysis of the cremaster microcirculation did not show spontaneous
      activation in the absence of AnxA1; however, superfusion with a direct-acting PMN
      activator (1 nM platelet-activating factor) revealed a subtle yet significant
      increase in leukocyte emigration, but not rolling or adhesion, in this genotype.
      Changes in the microcirculation were not secondary to alterations in hemodynamic
      parameters. The phenotype of the AnxA1 null PMN was investigated in two in vitro
      assays of cell activation (CD11b membrane expression and chemotaxis): the data
      obtained indicated a higher degree of cellular responses irrespective of the
      stimulus used. In conclusion, we have used a combination of inflammatory
      protocols and in vitro assays to address the specific counter-regulatory role of
      endogenous AnxA1, demonstrating its inhibitory control on PMN activation and the
      consequent impact on the inflamed microcirculation.

PMID- 16000392
TI  - Nitric oxide production is regulated by fever-range thermal stimulation of murine
      macrophages.
AB  - As macrophages are often called to function at times of elevated ambient
      temperature (e.g., during local inflammation or systemic fever), it is possible
      that their production of critical effector molecules, such as nitric oxide (NO)
      or inducible NO synthase (iNOS), is sensitive to physiological changes in
      temperature. To test this possibility, the threshold requirements for production
      of NO and iNOS in murine peritoneal macrophages maintained under normothermic
      conditions (37 degrees C) or following mild (fever-range) hyperthermia (39.5
      degrees C) were compared. We found that hyperthermia alone had no observable
      effect on basal NO production or iNOS protein or message. However, although
      interferon (IFN)-gamma and lipopolysaccharide (LPS) were needed to induce NO at
      37 degrees C, we observed that addition of only LPS was sufficient for production
      of NO if there were a pretreatment at 39.5 degrees C. Further, if IFN-gamma and
      LPS were given after thermal exposure, a substantial increase in NO and iNOS was
      observed over that seen using cells kept at normothermic conditions. Macrophages
      isolated from mice lacking heat shock factor-1 did not attenuate the ability of
      mild thermal stress to modulate NO production. Reverse transcriptase-polymerase
      chain reaction data revealed that thermal regulation of iNOS expression is not
      entirely at the transcriptional level, suggesting possible points of post
      transcriptional thermal sensitivity. These data support the concept that altering
      the thermal microenvironment is an important means by which the host can
      manipulate macrophage responses. Increases in temperature (e.g., during fever)
      may function to lower the activation threshold needed for production of effector
      molecules in times of infection.

PMID- 16000393
TI  - Morphine inhibits CD8+ T cell-mediated, noncytolytic, anti-HIV activity in
      latently infected immune cells.
AB  - Opiates have profound effects on the function of human immune cells and are a
      possible cofactor in the immunopathogenesis of human immunodeficiency virus (HIV)
      disease. We investigated the impact of morphine on CD8+ T cell-mediated,
      noncytotoxic, anti-HIV activity in latently infected human immune cells. Morphine
      inhibited the noncytotoxic, anti-HIV activity of CD8+ T cells in HIV latently
      infected cells (U1 and J1.1). Naltrexone abrogated the morphine-mediated,
      inhibitory effect on the noncytotoxic, anti-HIV activity of CD8+ T cells.
      Interferon-gamma (IFN-gamma), a potent antiviral cytokine produced by CD8+ T
      cells, was partially responsible for CD8+ T cell-mediated, noncytotoxic, anti-HIV
      activity. The anti-HIV activity of IFN-gamma was also compromised by morphine
      treatment. Further, morphine attenuated CD8+ T cell-mediated suppression of the
      HIV long-terminal repeat promoter activation. Morphine also inhibited CD8+ T cell
      induced expression of the signal transducer and activator of transcription-1, an
      important transcriptional factor in the IFN signaling pathway. These data provide
      additional evidence to support the notion that opioids play a role in impairing
      the anti-HIV function of the immune system.

PMID- 16000394
TI  - Cytokine induction of interleukin-24 in human peripheral blood mononuclear cells.
AB  - Interleukin-24 (IL-24) is a recently identified member of the IL-10 family of
      cytokines. It was originally identified as a tumor suppressor molecule, melanoma
      differentiation-associated gene 7, and then renamed IL-24 and classified as a
      cytokine, based on its chromosomal location in the IL-10 locus, its mRNA
      expression in leukocytes, and its secretory sequence elements. Here, we correlate
      the kinetics of IL-24 mRNA and protein expression in human peripheral blood
      mononuclear cells (PBMC) stimulated by polyclonal activators phytohemagglutinin
      (PHA) and lipopolysaccharide (LPS) or by allogeneic major histocompatibility
      complex. PHA-stimulated PBMC express IL-24 mRNA, reaching peak levels at 8-12 h
      after stimulation. Protein expression, as measured by intracellular flow
      cytometry, followed the message, reaching maximum expression at 24 h. Subset
      analysis of mitogen-stimulated PBMC showed that IL-24 was expressed primarily in
      T cells and macrophages. Expression of IL-24 in mitogen-stimulated PBMC is the
      result of cytokine stimulation. Individual cytokines including IL-2, IL-7, IL-15,
      tumor necrosis factor alpha, granulocyte macrophage-colony stimulating factor,
      and IL-1beta stimulate the expression of IL-24 mRNA and protein, whereas
      interferons and T helper cell type 2 cytokines fail to induce substantial IL-24.
      When LPS- or PHA-stimulated cells were treated with Actinomycin D, IL-24 mRNA
      persisted at high levels over the 4-h course of treatment. These data strongly
      suggest that the expression of IL-24 in human PBMC results from cytokine
      stimulation and is regulated at the post-transcriptional level through
      stabilization of IL-24 mRNA.

PMID- 16000395
TI  - Recombinant dimeric MHC antigens protect cardiac allografts from rejection and
      visualize alloreactive T cells.
AB  - Monomeric and dimeric soluble major histocompatibility complex (MHC) molecules
      down-regulate activated T cells in an antigen-specific manner in vitro. This
      property could be exploited to modulate alloresponses in vivo but has remained
      difficult to demonstrate. Here, intraperitoneal infusion of a Lewis-derived rat
      MHC class I molecule, RT1.A(l)-Fc, in Dark Agouti (RT1.A(a)) recipient rats
      prolonged cardiac graft survival, which led to permanent engraftment. This effect
      was mediated by T cell impairment of target cell lysis by CD8+ T cells and down
      regulation of interferon-gamma production by CD4+ T cells. The binding of the
      dimeric MHC allowed ex vivo visualization of alloreactive T cells in peripheral
      blood, splenocytes, and allografts, revealing low frequency of alloreactive CD8+
      T cells after establishment of permanent engraftment of cardiac allografts. Thus,
      these data show the potential of dimeric MHC molecules to promote graft survival
      and allow visualization of alloreactive T cells.

PMID- 16000396
TI  - CD8+ T cells produce IL-2, which is required for CD(4+)CD25+ T cell regulation of
      effector CD8+ T cell development for contact hypersensitivity responses.
AB  - Interleukin (IL)-2 functions to promote, as well as down-regulate, expansion of
      antigen-reactive CD4+ and CD8+ T cells, but the role of IL-2 in hapten-specific
      CD8+ T cell priming for contact hypersensitivity (CHS) responses remains
      untested. Using enzyme-linked immunospot to enumerate numbers of hapten-specific
      CD4+ and CD8+ T cells producing IL-2 in hapten-sensitized mice, the number of IL
      2-producing CD8+ T cells was tenfold that of CD4+ T cells. Hapten-primed CD4+ T
      cells produced low amounts of IL-2 during culture with hapten-presenting
      Langerhans cells, whereas production by hapten-primed CD8+ T cells was fivefold
      greater. CD8+ T cells did not express CD25 during hapten priming, but treatment
      with anti-IL-2 or anti-CD25 monoclonal antibodies during hapten sensitization
      increased hapten-specific effector CD8+ T cells as well as the magnitude and
      duration of the CHS response. These results indicate that CD8+ T cells are the
      primary source of IL-2 and that this IL-2 is required for the function of a
      population of CD(4+)CD25+ T cells to restrict the development of the hapten
      reactive effector CD8+ T cells that mediate CHS responses.

PMID- 16000397
TI  - Array-based comparative genomic hybridization reveals recurrent chromosomal
      aberrations and Jab1 as a potential target for 8q gain in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide. We
      have previously characterized global gene expression patterns in HCC using
      microarrays. Here, we report the analysis of genomic DNA copy number among 49 HCC
      samples using BAC array-based comparative genomic hybridization (CGH). We
      observed recurrent and characteristic chromosomal aberrations, including frequent
      DNA copy number gains of 1q, 6p, 8q and 20q, and losses of 4q, 8p, 13q, 16q and
      17p. We correlated gene expression with array CGH data, and identified a set of
      genes whose expression levels correlated with common chromosomal aberrations in
      HCC. Especially, we noticed that high expression of Jab1 in HCC significantly
      correlated with DNA copy number gain at 8q. Quantitative microsatellite analysis
      further confirmed DNA copy number gain at the Jab1 locus. Overexpression of Jab1
      in HCC was also validated using real-time RT-PCR, and Jab1 protein levels were
      studied by immunohistochemistry on tissue microarrays. Functional analysis in HCC
      cell lines demonstrated that Jab1 may regulate HCC cell proliferation, thereby
      having a potential role in HCC development. In conclusion, this study shows that
      array-based CGH provides high resolution mapping of chromosomal aberrations in
      HCC, and demonstrates the feasibility of correlating array CGH data with gene
      expression data to identify novel oncogenes and tumor suppressor genes.

PMID- 16000398
TI  - Quantitative determination of urinary N7-ethylguanine in smokers and non-smokers
      using an isotope dilution liquid chromatography/tandem mass spectrometry with on
      line analyte enrichment.
AB  - Previous studies demonstrated the presence of unknown direct-acting ethylating
      agents arising from cigarette smoke. We hypothesized that such agents would also
      lead to ethylation of guanine in DNA followed by depurination/repair and
      excretion of N7-ethylguanine (N7-EtG) in urine. In this study, a highly specific
      and sensitive liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method
      was firstly developed for measuring urinary N7-EtG. With the use of an isotope
      internal standard (15N5-N7-EtG) and on-line enrichment techniques, the detection
      limit of this method was estimated as 0.59 pg/ml (0.33 pmol) on-column. This
      method was then applied to measure urinary samples obtained from 35 non-smokers
      and 32 smokers with dietary control. The results showed that the mean urinary
      levels of N7-EtG were 85.5+/-105 and 28.1+/-19.4 pg/mg creatinine for smokers and
      non-smokers, respectively. Smokers had about three times higher level of N7-EtG
      than non-smokers (P<0.005). It was further noted that the urinary level of N7-EtG
      was significantly associated with cotinine for smokers (r=0.49, P<0.005). Taken
      together, this is the first study that demonstrated the presence of N7-EtG in
      urine, and that cigarette smoke was highly responsible for the increased urinary
      excretion of N7-EtG. This non-invasive measurement of urinary N7-EtG would be
      useful for the surveillance of ethylating agent exposure and its associated
      cancer risk in the future.

PMID- 16000399
TI  - Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the
      dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their
      secretion into breast milk.
AB  - The breast cancer resistance protein (BCRP/ABCG2) usually protects the body from
      a wide variety of environmental and dietary xenotoxins by reducing their net
      uptake from intestine and by increasing their hepatobiliary, intestinal and renal
      elimination. BCRP is also highly expressed in lactating mammary glands in mice,
      and this expression is conserved in cows and humans. As a result, BCRP substrates
      can be secreted into milk. We investigated whether different classes of dietary
      carcinogens are substrates of Bcrp1/BCRP and the implications for systemic
      exposure and breast milk contamination. Using polarized cell lines, we found that
      Bcrp1 transports the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline
      (IQ) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and the potent
      human hepatocarcinogen aflatoxin B1, and decreases their cellular accumulation up
      to 10-fold. In vivo pharmacokinetic studies showed that [14C]IQ, [14C]Trp-P-1 and
      [3H]aflatoxin B1 plasma levels were substantially lower in wild-type compared
      with Bcrp1-/- mice, after both oral and intravenous administration, demonstrating
      that Bcrp1 restricts systemic exposure to these carcinogens. Moreover, Bcrp1
      mediates transfer of [14C]IQ, [14C]Trp-P-1 and [3H]aflatoxin into milk, with
      3.4+/-0.6, 2.6+/-0.3 and 3.8+/-0.5-fold higher milk to plasma ratios,
      respectively, in lactating wild-type versus Bcrp1-/- mice. We have thus
      identified Bcrp1/BCRP as one of the molecular mechanisms by which heterocyclic
      amines and aflatoxin are transferred into milk, thereby posing a health risk to
      breast-fed infants and dairy consumers. Paradoxically, Bcrp1/BCRP appears to have
      both protective and adverse roles with respect to exposure to dietary
      carcinogens.

PMID- 16000400
TI  - The association of DNA-dependent protein kinase activity with chromosomal
      instability and risk of cancer.
AB  - The DNA double-strand breaks (DSBs) repair pathway has been implicated in
      maintaining genomic integrity via suppression of chromosomal rearrangements. DNA
      dependent protein kinase (DNA-PK) has an important role with DNA DSBs repair. In
      this study, 93 of untreated cancer patients and 41 of cancer-free healthy
      volunteers were enrolled. Peripheral blood was collected, separated and
      centrifuged; DNA-PK activity was measured by DNA-pull-down assay. The expressions
      of DNA-PKcs, Ku70 and Ku86 were examined by RT-PCR assay and western blotting.
      Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activities
      of peripheral blood lymphocytes (PBL) in patients with uterine cervix or breast
      cancer were significantly lower than those in normal volunteers. Age and smoking
      had no association with DNA-PK activity, whereas DNA-PK activity and the
      expression of Ku70, Ku86 and DNA-PKcs in RT-PCR were interrelated. A similar
      tendency was seen in western blot assay but less clear than in RT-PCR. Therefore,
      the association between DNA-PK activity and expression of DNA-PK in protein level
      could not be concluded. The frequency of chromosome aberration, such as dicentric
      chromosomes and excess fragment increased as the DNA-PK activity decreased. In
      conclusion, DNA-PK activity is associated with chromosomal instability. DNA-PK
      activity in PBL is associated with risk of breast and uterine cervix cancer. DNA
      PK activity in PBL can be used to select individuals for whom an examination
      should be performed because of their increased susceptibility to breast and
      uterine cervix cancer.

PMID- 16000401
TI  - Production of chemokine CXCL1/KC by okadaic acid through the nuclear factor
      kappaB pathway.
AB  - The murine chemokine CXCL1/KC is known as a chemoattractant for neutrophil
      infiltration and as a promoter of tumor growth. To determine its relevance in
      tumorigenesis, we first asked whether okadaic acid (OKA), a natural tumor
      promoter and a potent protein phosphatase 1 and 2A inhibitor, stimulates KC
      expression and if it does, through what pathway, in a promotable mouse epidermal
      like JB6 cell line commonly used for studying molecules related to tumor
      promotion. We found that OKA stimulated the de novo synthesis of KC mRNA and
      protein in a dose- and time-dependent manner. To determine the mechanism by which
      OKA stimulated the expression of KC at the transcriptional level, transient
      transfection assays using serially deleted sections of KC promoter fused to
      luciferase reporter gene were performed. These studies showed that
      transactivation of KC promoter by OKA specifically involved the region between 
      104 and -59 containing the two nuclear factor-kappaB (NF-kappaB) response
      elements (kappaB1 and kappaB2). Further analyses using the mutated NF-kappaB
      response elements kappaB1 and kappaB2 indicated that both regions were required
      for optimum transactivation of KC by OKA with the former NF-kappaB response
      element playing a more significant role in regulating KC expression. Gel-shift
      and supershift analyses demonstrated the involvement of three NF-kappaB subunits,
      p65, p50 and c-Rel, with p65 as the major subunit in the NF-kappaB dimer complex.
      Additionally, immunohistochemistry and western blot analyses confirmed the
      presence of p65 in the nucleus with its transactivation domain phosphorylated at
      serine 536. In summary, this is the first report to show that the tumor promoter
      OKA can stimulate the de novo synthesis and secretion of KC, and that this
      stimulation is mediated through the NF-kappaB pathway in JB6 cells.

PMID- 16000402
TI  - Permeation and reservoir formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the
      presence of ethanol and menthol.
AB  - Environmental influences may affect carcinogen absorption and residency in the
      tissues of the aero-digestive tract. We quantified the effect of ethanol and
      menthol on the rates of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and
      benzo[a]pyrene (B[a]P) absorption using a fully validated in vitro diffusion
      system, capable of accurately and precisely quantifying tobacco carcinogen
      permeation and reservoir formation in porcine esophageal mucosa. Confocal
      microscopy was employed to visualize the location of B[a]P in the exposed
      membranes. Markedly different extents of permeation and reservoir formation for
      the tobacco carcinogens were recorded in the presence of ethanol and menthol. The
      water-soluble NNK permeated the membrane rapidly, while the lipophilic B[a]P did
      not appreciably diffuse through the tissue. Significantly different extents of
      reservoir formation were observed for the different carcinogens and in the
      presence of the different penetration-enhancer solvents. Alcohol (at 5%
      concentration) did not influence the permeation or reservoir formation of NNK. A
      mentholated donor solution (0.08%) both decreased the flux of NNK and
      significantly increased the tissue reservoir formation. The magnitude of the
      reservoir formed by B[a]P was relatively extensive (even though membrane
      permeation rates were negligible), being greatest in the presence of both ethanol
      and menthol. This suggests synergy between the two penetration-enhancer species
      acting on this carcinogen. Confocal microscopy studies confirmed that there was
      an appreciable intra-cellular, and specifically nuclear, association of the B[a]P
      species during the reservoir formation process. The aqueous solubility of the
      diffusing species and the presence of penetration enhancers appeared to be key
      factors in the absorption and cellular binding processes. The results presented
      support the hypothesis that the use of mentholated cigarettes, or the concomitant
      consumption of alcohol while smoking, may have marked effects on the fate of
      tobacco chemicals. This finding may help to explain elevated rates of esophageal
      squamous cell carcinoma in African Americans.

PMID- 16000403
TI  - Extended-spectrum beta-lactamases in non-typhoidal Salmonella spp. isolated in
      the UK are now a reality: why the late arrival?
AB  - In February 2004, we reported the first recognition of the presence of an
      extended-spectrum beta-lactamase (ESBL) in non-typhoidal Salmonella spp. in the
      UK; the beta-lactamase was TEM-52. Six months later, an SHV-derived ESBL (SHV-12)
      was detected in a salmonella strain isolated in York and 6 months after that we
      have just identified CTX-M-type beta-lactamases in Scottish isolates of
      Salmonella enterica subsp. enterica serovar Typhimurium and Salmonella Virchow
      (unpublished results). A very recent retrospective study of UK isolates suggests
      that they may have been in the population for some years but have gone
      undetected. Even so, compared with reports of ESBLs in Salmonella spp. elsewhere,
      these results are suggestive of a delayed emergence of the ESBL phenotype in non
      typhoidal Salmonella spp. in the UK. Should the British congratulate themselves
      on warding off the emergence of these important resistance mechanisms in
      Salmonella spp., or is the sudden revelation of three of the major ESBL types a
      cause for concern?

PMID- 16000404
TI  - An increase in telomere sister chromatid exchange in murine embryonic stem cells
      possessing critically shortened telomeres.
AB  - Telomerase deficiency leads to a progressive loss of telomeric DNA that
      eventually triggers cell apoptosis in human primary cells during prolonged growth
      in culture. Rare survivors can maintain telomere length through either activation
      of telomerase or recombination-based telomere lengthening, and thus proliferate
      indefinitely. We have explored the possibility that telomeres may be maintained
      through telomere sister chromatid exchange (T-SCE) in murine telomere reverse
      transcriptase-deficient (mTert-/-) splenocytes and ES cells. Because telomerase
      deficiency leads to gradual loss of telomeric DNA in mTert-/- splenocytes and ES
      cells and eventually to chromosomes with telomere signal-free ends (SFEs), we
      examined these cell types for evidence of sister chromatid exchange at telomeres,
      and observed an increase in T-SCEs only in a subset of mTert-/- splenocytes or ES
      cells that possessed multiple SFEs. Furthermore, T-SCEs were more often detected
      in ES cells than in splenocytes that harbored a similar frequency of SFEs. In
      mTert heterozygous (mTert+/-) ES cells or splenocytes, which are known to exhibit
      a decrease in average telomere length but no SFEs, no increase in T-SCE was
      observed. In addition to T-SCE, other genomic rearrangements (i.e., SCE) were
      also significantly increased in mTert-/- ES cells possessing critically short
      telomeres, but not in splenocytes. Our results suggest that animals and cell
      culture differ in their ability to carry out genomic rearrangements as a means of
      maintaining telomere integrity when telomeres become critically shortened.

PMID- 16000405
TI  - Restriction mapping in nanofluidic devices.
AB  - We have performed restriction mapping of DNA molecules using restriction
      endonucleases in nanochannels with diameters of 100-200 nm. The location of the
      restriction reaction within the device is controlled by electrophoresis and
      diffusion of Mg2+ and EDTA. We have successfully used the restriction enzymes
      SmaI, SacI, and PacI, and have been able to measure the positions of restriction
      sites with a precision of approximately 1.5 kbp in 1 min using single DNA
      molecules.

PMID- 16000406
TI  - Common pathways in circadian and cell cycle clocks: light-dependent activation of
      Fos/AP-1 in zebrafish controls CRY-1a and WEE-1.
AB  - The cell cycle and the circadian clock are endogenous pacemakers, which coexist
      in most eukaryotic cells and share a number of conceptual features. In the
      zebrafish, light directly regulates the timing of both clocks, although the
      signaling and transcriptional pathways that convey photic information to
      essential nuclear regulators have yet to be deciphered. We have previously
      established the Z3 cell line, which recapitulates the features of zebrafish
      circadian clock and represents an ideal system to study light-dependent signaling
      and gene regulation. We conducted a search for light-responsive transcription
      factors and found that AP-1 DNA binding is highly induced. Light induces the
      expression of zWee1, a cell cycle gene essential for G2/M transition, and zCry1a,
      a clock gene of the feedback regulatory loop. We have found consensus AP-1 sites
      in the regulatory regions of both zWee1 and zCry1a genes, and we show that light
      inducibility of both genes is abrogated by inhibition of AP-1 function. Light
      also elicits chromatin remodeling by stimulating hyperacetylation at Lys-14 of
      histone H3 at both zWee1 and zCry1a promoters, as assessed by chromatin
      immunoprecipitation assays by using anti-Fos antibody. These findings provide
      strong evidence that circadian and cell cycle clocks share unique light
      responsive pathways in zebrafish.

PMID- 16000407
TI  - An algorithm for progressive multiple alignment of sequences with insertions.
AB  - Dynamic programming algorithms guarantee to find the optimal alignment between
      two sequences. For more than a few sequences, exact algorithms become
      computationally impractical, and progressive algorithms iterating pairwise
      alignments are widely used. These heuristic methods have a serious drawback
      because pairwise algorithms do not differentiate insertions from deletions and
      end up penalizing single insertion events multiple times. Such an unrealistically
      high penalty for insertions typically results in overmatching of sequences and an
      underestimation of the number of insertion events. We describe a modification of
      the traditional alignment algorithm that can distinguish insertion from deletion
      and avoid repeated penalization of insertions and illustrate this method with a
      pair hidden Markov model that uses an evolutionary scoring function. In
      comparison with a traditional progressive alignment method, our algorithm infers
      a greater number of insertion events and creates gaps that are phylogenetically
      consistent but spatially less concentrated. Our results suggest that some
      insertion/deletion "hot spots" may actually be artifacts of traditional alignment
      algorithms.

PMID- 16000408
TI  - Inhibition of IFN-alpha signaling by a PKC- and protein tyrosine phosphatase SHP
      2-dependent pathway.
AB  - Cytokine signaling by the Jak-STAT pathway is subject to complex negative
      regulation that limits the amplitude and duration of signal transduction.
      Inhibition of signaling also mediates negative crosstalk, whereby factors with
      opposing biological activities crossinhibit each other's function. Here, we
      investigated a rapidly inducible mechanism that inhibited Jak-STAT activation by
      IFN-alpha, a cytokine that is important for antiviral responses, growth control,
      and modulation of immune responses. IFN-alpha-induced signaling and gene
      activation were inhibited by ligation of Fc receptors and Toll-like receptors 7
      and 8 in a PKCbeta-dependent manner. Neither PKCbeta nor PKCdelta influenced
      responses of cells treated with IFN-alpha alone. Inhibition of IFN-alpha
      signaling correlated with suppression of IFN-alpha-dependent antiviral responses.
      PKC-mediated inhibition did not require de novo gene expression but involved the
      recruitment of PKCbeta to the IFN-alpha receptor and interaction with protein
      tyrosine phosphatase SHP-2, resulting in augmented phosphatase activity. PKC
      mediated inhibition of IFN-alpha signaling was abolished in SHP-2-deficient
      cells, demonstrating a pivotal role for SHP-2 in this inhibitory pathway.
      Together, our data describe a rapidly inducible, direct mechanism of inhibition
      of Jak-STAT signaling mediated by a PKCbeta-SHP-2 signaling pathway.

PMID- 16000409
TI  - APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast.
AB  - Human cells harbor a variety of factors that function to block the proliferation
      of foreign nucleic acid. The APOBEC3G enzyme inhibits the replication of
      retroviruses by deaminating nascent retroviral cDNA cytosines to uracils, lesions
      that can result in lethal levels of hypermutation. Here, we demonstrate that
      APOBEC3G is capable of deaminating genomic cytosines in Saccharomyces cerevisiae.
      APOBEC3G expression caused a 20-fold increase in frequency of mutation to
      canavanine-resistance, which was further elevated in a uracil DNA glycosylase
      deficient background. All APOBEC3G-induced base substitution mutations mapped to
      the nuclear CAN1 gene and were exclusively C/G --> T/A transition mutations
      within a 5'-CC consensus. The APOBEC3G preferred sites were found on both strands
      of the DNA duplex, but were otherwise located in hotspots nearly identical to
      those found previously in retroviral cDNA. This unique genetic system further
      enabled us to show that expression of APOBEC3G or its homolog APOBEC3F was able
      to inhibit the mobility of the retrotransposon Ty1 by a mechanism that involves
      the deamination of cDNA cytosines. Thus, these data expand the range of likely
      APOBEC3 targets to include nuclear DNA and endogenous retroelements, which have
      pathological and physiological implications, respectively. We postulate that the
      APOBEC3-dependent innate cellular defense constitutes a tightly regulated arm of
      a conserved mobile nucleic acid restriction mechanism that is poised to limit
      internal as well as external assaults.

PMID- 16000410
TI  - Highly pathogenic H5N1 influenza virus infection in migratory birds.
AB  - H5N1 avian influenza virus (AIV) has emerged as a pathogenic entity for a variety
      of species, including humans, in recent years. Here we report an outbreak among
      migratory birds on Lake Qinghaihu, China, in May and June 2005, in which more
      than a thousand birds were affected. Pancreatic necrosis and abnormal
      neurological symptoms were the major clinical features. Sequencing of the
      complete genomes of four H5N1 AIV strains revealed them to be reassortants
      related to a peregrine falcon isolate from Hong Kong and to have known highly
      pathogenic characteristics. Experimental animal infections reproduced typical
      highly pathogenic AIV infection symptoms and pathology.

PMID- 16000411
TI  - Toward standardization of diagnostic PCR testing of fecal samples: lessons from
      the detection of salmonellae in pigs.

PMID- 16000412
TI  - Evaluation of PCR for diagnosis of Indian kala-azar and assessment of cure.
AB  - This study was done to evaluate PCR with Ld1 primers for the diagnosis of Indian
      visceral leishmaniasis (VL) and to assess its role in prediction of the disease
      outcome. The PCR assay was performed with DNA isolated from the peripheral blood
      of parasitologically confirmed cases of VL before the initiation of treatment,
      just after the end of treatment, and at 3 and 6 months of follow-up. The
      pretreatment PCR result was positive for 100 of 101 patients (sensitivity, 99%;
      confidence interval [CI], 94 to 100%). None of the 150 negative controls tested
      were PCR positive (specificity, 100%; CI, 96.8 to 100%). Of 60 patients who were
      treated at our center, 51 (85%; CI, 73 to 93%) became negative immediately after
      treatment and continued to be negative at 3 and 6 months of follow-up. At the 3
      month follow-up, two of the remaining nine patients were PCR positive, making 58
      (96.7%; CI, 87 to 100%) patients PCR negative. At the 6-month follow-up, all
      patients became PCR negative. One patient who was PCR negative immediately after
      the end of treatment relapsed 11 months later. This limited prospective study
      with VL patients suggests that the PCR assay is a highly sensitive and specific
      (99% and 100%, respectively) tool for the diagnosis of VL. In the majority of
      patients, it can identify a successful disease outcome; however, its translation
      into the field setting remains a major challenge.

PMID- 16000413
TI  - Identification of novel human hepatitis E virus (HEV) isolates and determination
      of the seroprevalence of HEV in Korea.
AB  - Hepatitis E virus (HEV) was originally identified as the causative agent of
      enterically transmitted non-A, non-B hepatitis. Recently, HEV isolates were
      subsequently identified in humans and swine in many countries, including Korea.
      Also, public concerns regarding HEV as a potential zoonotic agent have been
      increasing. Therefore, we attempted to identify HEV from Korean sera and compare
      the nucleotide sequences with those of previously identified HEV isolates from
      other countries. In our study, viral RNA was purified from 568 human sera
      collected from different regions of Korea. Nested PCR and reverse transcriptase
      PCR were developed based on the nucleotide sequences of open reading frame 2 (ORF
      2) of U.S. and Japanese HEV isolates from humans and Korean HEV isolates from
      swine. After amplification of the HEV ORF 2 gene from 14 serum samples that were
      collected mainly from rural areas (2.64% prevalence of HEV viremia), the gene was
      cloned and sequenced. The isolates were classified into seven different strains,
      all of which belonged to genotype III. The human isolates we identified were
      closely related to three Korean swine isolates, with 99.2 to 92.9% nucleotide
      sequence homology. Our isolates were also related to the Japanese and U.S. HEV
      isolates, with 99.6 to 97.9% amino acid sequence homology. Human sera were
      collected from 361 individuals from community health centers and medical
      colleges. With respect to seroprevalence, 11.9% of the Korean population had anti
      HEV immunoglobulin G (IgG). In individuals ranging in age from 40 to over 60
      years, the prevalence of anti-HEV IgG was demonstrated by a seroprevalence of
      almost 15%, especially among populations in rural areas. This is the first report
      on the identification of human HEV in Korea. Overall, this study demonstrates
      that subclinical HEV infections may prevail in human populations in Korea and
      that there is a strong possibility that HEV is a zoonotic agent.

PMID- 16000414
TI  - Molecular detection and quantitative analysis of the entire spectrum of human
      adenoviruses by a two-reaction real-time PCR assay.
AB  - Adenoviruses (AdV) can cause life-threatening infections in immunosuppressed
      patients. Reliable diagnostic tests are therefore of paramount importance.
      Apparently, any of the six AdV species (A to F), currently comprising 51
      different serotypes, can play a clinically important role in patients with
      impaired immune response. It is imperative therefore that diagnostic assays cover
      the entire spectrum of these viruses. We have sequenced presumably conserved
      regions of the adenoviral genome in all AdV serotypes. Based on the complete
      sequence information of the hexon gene, we were able to develop a two-reaction
      real-time PCR assay covering all human adenoviruses with equally high specificity
      and sensitivity. The detection systems were tested using reference strains for
      all 51 serotypes and >1,000 clinical samples derived from peripheral blood and
      stool specimens from pediatric patients after allogeneic stem cell
      transplantation. The two-reaction assay presented permits highly specific
      detection and quantification of adenoviral DNA of any serotype. From the
      perspective of routine clinical diagnosis, the assay represents an important
      improvement over existing approaches by providing a sensitive and economic
      technique for early detection and monitoring of adenoviral infections.

PMID- 16000415
TI  - Differential sensitivities of severe acute respiratory syndrome (SARS)
      coronavirus spike polypeptide enzyme-linked immunosorbent assay (ELISA) and SARS
      coronavirus nucleocapsid protein ELISA for serodiagnosis of SARS coronavirus
      pneumonia.
AB  - The use of recombinant severe acute respiratory syndrome-coronavirus (SARS-CoV)
      nucleocapsid protein (N) enzyme-linked immunosorbent assay (ELISA)-based antibody
      and antigen tests for diagnosis of SARS-CoV infections have been widely reported.
      However, no recombinant SARS-CoV spike protein (S)-based ELISA is currently
      available. In this article, we describe the problems and solutions of setting up
      the recombinant SARS-CoV S-based ELISA for antibody detection. The SARS-CoV S
      based immunoglobulin M (IgM) and IgG ELISAs were evaluated and compared with the
      corresponding N-based ELISA for serodiagnosis of SARS-CoV pneumonia, using sera
      from 148 healthy blood donors who donated blood 3 years ago as controls and 95
      SARS-CoV pneumonia patients in Hong Kong. Results obtained by the recombinant S
      (rS)-based IgG ELISA using the regenerated S prepared by dialysis with decreasing
      concentrations of urea or direct addition of different coating buffers, followed
      by addition of different regeneration buffer, identified 4 M urea and 1 M
      sarcosine for plate coating and no regeneration buffer as the most optimal
      conditions for antibody detection. The specificities of the S-based ELISA for IgG
      and IgM detection were 98.6% and 93.9%, with corresponding sensitivities of 58.9%
      and 74.7%, respectively. The sensitivity of the rN IgG ELISA (94.7%) is
      significantly higher than that of the rS IgG ELISA (P < 0.001), whereas the
      sensitivity of the rS IgM ELISA is significantly higher than that of the rN IgM
      ELISA (55.2%) (P < 0.01). An ELISA for detection of IgM against S and N could be
      more sensitive than one that detects IgM against N alone for serodiagnosis of
      SARS-CoV pneumonia.

PMID- 16000416
TI  - Effect of pH and antibiotics on microbial overgrowth in the stomachs and duodena
      of patients undergoing percutaneous endoscopic gastrostomy feeding.
AB  - Enteral nutrition via a percutaneous endoscopic gastrostomy (PEG) tube is often
      part of management in patients with dysphagia due to neurological or
      oropharyngeal disease. Gastrostomy placement can affect normal innate defense
      mechanisms in the upper gut, resulting in bacterial overgrowth. In this study
      microbiological investigations were done with gastric and duodenal aspirates from
      20 patients undergoing PEG tube placement and PEG tubes from 10 patients
      undergoing tube replacement. Aspirate and PEG tube microbiotas were assessed by
      using viable counts and selective solid media followed by aerobic and anaerobic
      incubation to assess cell viabilities. The antibiotic susceptibility profiles of
      the isolates were determined by the disk diffusion method, and gas chromatography
      was used to study the bacterial metabolic products in the aspirates. The
      aspirates and PEG tubes contained mainly streptococci, staphylococci,
      lactobacilli, yeasts, and enterobacteria. Enterococci were detected only in PEG
      tube biofilms and not in aspirates. Gastric pH affected the composition of the
      aspirate microbiotas but not the total microbial counts. Staphylococci,
      Escherichia coli, and Candida spp. were isolated only from antibiotic-treated
      patients, despite the sensitivities of the bacteria to the agents used.
      Antibiotic treatment had no effect on the incidence of infection or the length of
      hospital stay in these patients.

PMID- 16000417
TI  - Detection and typing of integrons in epidemic strains of Acinetobacter baumannii
      found in the United Kingdom.
AB  - Integrons were sought in Acinetobacter isolates from hospitals in the United
      Kingdom by integrase gene PCR. Isolates were compared by pulsed-field gel
      electrophoresis, and most belonged to a small number of outbreak strains or
      clones of A. baumannii, which are highly successful in the United Kingdom. Class
      1 integrons were found in all of the outbreak isolates but in none of the
      sporadic isolates. No class 2 integrons were found. Three integrons were
      identified among the main outbreak strains and clones. While a particular
      integron was usually associated with a strain or clone, some members carried a
      different integron. Some integrons were associated with more than one strain. The
      cassette arrays of two of the integrons were very similar, both containing gene
      aacC1, which confers resistance to gentamicin, two open reading frames coding for
      unknown products (orfX, orfX'), and gene aadA1a, which confers resistance to
      spectinomycin and streptomycin. The larger of these integrons had two copies of
      the first (orfX) of the gene cassettes coding for unknown products. The third
      integron, with a cassette array containing gene aacA4, which codes for amikacin,
      netilmicin, and tobramycin resistance; a chloramphenicol acetyltransferase,
      catB8; and gene aadA1, conferring resistance to spectinomycin and streptomycin,
      was associated with an OXA-23 carbapenemase-producing clone, which has spread
      rapidly in hospitals in the United Kingdom during 2003 and 2004. These integron
      cassette arrays have been found in other outbreak strains of A. baumannii from
      other countries. We conclude that integrons are useful markers for epidemic
      strains of A. baumannii and that integron typing provides valuable information
      for epidemiological studies.

PMID- 16000418
TI  - Genomic and bioinformatics analyses of HAdV-4vac and HAdV-7vac, two human
      adenovirus (HAdV) strains that constituted original prophylaxis against HAdV
      related acute respiratory disease, a reemerging epidemic disease.
AB  - Vaccine strains of human adenovirus serotypes 4 and 7 (HAdV-4vac and HAdV-7vac)
      have been used successfully to prevent adenovirus-related acute respiratory
      disease outbreaks. The genomes of these two vaccine strains have been sequenced,
      annotated, and compared with their prototype equivalents with the goals of
      understanding their genomes for molecular diagnostics applications, vaccine
      redevelopment, and HAdV pathoepidemiology. These reference genomes are archived
      in GenBank as HAdV-4vac (35,994 bp; AY594254) and HAdV-7vac (35,240 bp;
      AY594256). Bioinformatics and comparative whole-genome analyses with their
      recently reported and archived prototype genomes reveal six mismatches and four
      insertions-deletions (indels) between the HAdV-4 prototype and vaccine strains,
      in contrast to the 611 mismatches and 130 indels between the HAdV-7 prototype and
      vaccine strains. Annotation reveals that the HAdV-4vac and HAdV-7vac genomes
      contain 51 and 50 coding units, respectively. Neither vaccine strain appears to
      be attenuated for virulence based on bioinformatics analyses. There is evidence
      of genome recombination, as the inverted terminal repeat of HAdV-4vac is
      initially identical to that of species C whereas the prototype is identical to
      species B1. These vaccine reference sequences yield unique genome signatures for
      molecular diagnostics. As a molecular forensics application, these references
      identify the circulating and problematic 1950s era field strains as the original
      HAdV-4 prototype and the Greider prototype, from which the vaccines are derived.
      Thus, they are useful for genomic comparisons to current epidemic and reemerging
      field strains, as well as leading to an understanding of pathoepidemiology among
      the human adenoviruses.

PMID- 16000419
TI  - Comparison of multiple-locus variable-number tandem-repeat analysis with pulsed
      field gel electrophoresis, spa typing, and multilocus sequence typing for clonal
      characterization of Staphylococcus aureus isolates.
AB  - Multiple-locus variable-number tandem-repeat analysis (MLVA), a new PCR-based
      method of typing Staphylococcus aureus, was compared to pulsed-field gel
      electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) on a
      group of 59 S. aureus (mostly methicillin-resistant) clinical isolates. The aim
      of the study was to establish possible criteria of clustering MLVA patterns and
      to check concordance levels between the results produced by MLVA and the three
      other typing methods. As in our earlier study, MLVA turned out to have
      discriminatory power similar to that of PFGE. Comparison of data obtained by the
      two approaches allowed us to propose a 70% or ca. 80% cutoff value of the
      similarity between two MLVA patterns, depending on a cutoff level applied to
      interpret the PFGE results, 75% or ca. 90%, respectively. The cutoff values
      corresponded to the difference of up to six or four bands, respectively, among
      maximum 14 bands in total produced by two isolates in the analysis. The MLVA
      clusters matched well those obtained by PFGE, and they were also consistent in
      general with clusters generated by spa typing and MLST, these latter methods
      characterized lower resolution. Our results suggest that MLVA may be reliable in
      shorter-term S. aureus epidemiological studies, including analyses of outbreaks
      and hospital-to-hospital strain transmission events. Well-known advantages of
      typing methods based on PCR (low cost, short time, and easiness of performance)
      make MLVA a method that may be useful in a variety of laboratories, including
      those performing routine microbiological analyses within medical centers.

PMID- 16000420
TI  - Variations in emm type among group A streptococcal isolates causing invasive or
      noninvasive infections in a nationwide study.
AB  - Since the late 1980s several studies have described the increased incidence and
      severity of invasive group A streptococcal (GAS) infections. However, most
      studies on GAS pathogenesis have focused on information obtained during
      outbreaks. We analyzed isolate distribution and host susceptibility as part of a
      nationwide prospective surveillance study performed between January 2001 and
      August 2002. GAS isolates collected from 201 patients with invasive infections,
      335 patients with noninvasive infections, and 17 asymptomatic carriers were
      characterized with respect to their emm types and superantigen genotypes. The
      superantigen-neutralizing capacity and levels of antibodies against streptolysin
      O and DNAse B were determined for isolates from the sera from 36 invasive cases
      and 91 noninvasive cases. emm type 1 (emm-1) isolates were significantly more
      common among invasive cases, whereas emm-4, emm-6, and emm-12 dominated among the
      noninvasive cases. The distributions of the phage-associated superantigen genes
      (speA, speC, speH, speI, ssa) differed among invasive and noninvasive isolates,
      mainly due to their linkage to certain emm types. No significant differences in
      serum superantigen-neutralizing capacities were observed. The levels of anti
      streptolysin O and anti-DNAse B antibodies were highest in the sera from invasive
      cases. Our study emphasizes the importance of obtaining data during years with
      stable incidences, which will enable evaluation of future outbreak data.

PMID- 16000421
TI  - AmpC disk test for detection of plasmid-mediated AmpC beta-lactamases in
      Enterobacteriaceae lacking chromosomal AmpC beta-lactamases.
AB  - Although plasmid-mediated AmpC beta-lactamases were first reported in the late
      1980s, many infectious disease personnel remain unaware of their clinical
      importance. These enzymes are typically produced by isolates of Escherichia coli,
      Klebsiella spp., Proteus mirabilis, and Salmonella spp. and are associated with
      multiple antibiotic resistance that leaves few therapeutic options. Plasmid
      mediated AmpC beta-lactamases have been associated with false in vitro
      susceptibility to cephalosporins. Many laboratories do not test for this
      resistance mechanism because current tests are inconvenient, subjective, lack
      sensitivity and/or specificity, or require reagents that are not readily
      available. In this study a new test, the AmpC disk test, based on filter paper
      disks impregnated with EDTA, was found to be a highly sensitive, specific, and
      convenient means of detection of plasmid-mediated AmpC beta-lactamases in
      organisms lacking a chromosomally mediated AmpC beta-lactamase. Using cefoxitin
      insusceptibility as a screen, the test accurately distinguished AmpC and extended
      spectrum beta-lactamase production and differentiated AmpCs from non-beta
      lactamase mechanisms of cefoxitin insusceptibility, such as reduced outer
      membrane permeability. The test is a potentially useful diagnostic tool. It can
      provide important infection control information and help to ensure that infected
      patients receive appropriate antibiotic therapy.

PMID- 16000422
TI  - Drug resistance evolution of a Mycobacterium tuberculosis strain from a
      noncompliant patient.
AB  - The emergence and spread of multidrug-resistant (MDR) Mycobacterium tuberculosis
      (MT) represents a worldwide health care problem because of the difficulty in
      treating these infections. Development of drug resistance in MT arises mainly by
      mutation of chromosomal genes. To investigate the evolution of a MT population
      during a long-lasting infection, the phenotypic and genotypic changes in the drug
      resistance of 10 sequential MT isolates from a noncompliant chronically infected
      patient were investigated. During more than 12 years of active disease, a MDR
      population developed; molecular typing showed one single parental strain that
      infected the patient and persisted throughout the disease. Molecular analysis of
      the drug resistance-related genes revealed that discrete subpopulations evolved
      over time from the parental strain by acquiring and accumulating resistance
      conferring mutations to isoniazid, rifampin, and streptomycin. Overall, these
      observations indicate that during a chronic infection, several subpopulations may
      coexist in the same patient with different drug susceptibility profiles.

PMID- 16000423
TI  - Development of a quantitative real-time PCR assay for detection of Mycoplasma
      genitalium.
AB  - Mycoplasma genitalium is known to cause nonchlamydial, nongonococcal urethritis
      in men and to be associated with pelvic inflammatory disease in women. Specific
      and sensitive PCR methods are needed for diagnosis of this bacterium because it
      is very difficult to culture from patient samples. To determine the bacterial
      load in patients' specimens, a quantitative real-time LightCycler PCR was
      developed. The housekeeping gene gap encoding glyceraldehyde-3-phosphate
      dehydrogenase was chosen as the target gene. The assay could consistently detect
      five genome copies per reaction. To evaluate the PCR, we tested 246 selected
      urethral swab samples from men attending a clinic for sexually transmitted
      diseases. Eighty-two of the samples were found positive for M. genitalium by a
      conventional 16S rRNA gene PCR assay, whereas 164 samples were randomly chosen
      among those tested negative. Of the positive samples, 78 (95.1%) were found
      positive, whereas 6 (3.7%) of the negatives were found positive by the
      LightCycler assay. The patient samples were also tested with a quantitative
      TaqMan assay, and the bacterial load was compared to the LightCycler results. A
      good linear correlation between the LightCycler and the TaqMan assays was found
      with a correlation coefficient of 0.89 and a slope of 0.99. Significantly more M.
      genitalium-positive men had urethritis, discharge, and dysuria than had M.
      genitalium-negative men. The M. genitalium DNA load in samples from patients with
      urethritis was significantly higher than in samples from those without (61 and
      2.9 copies/microl, respectively [P = 0.0005]). This assay may prove useful in the
      monitoring of treatment and for optimizing sample preparation methods.

PMID- 16000424
TI  - Detection of Pseudomonas aeruginosa producing metallo-beta-lactamases in a large
      centralized laboratory.
AB  - Metallo-beta-lactamases (MBLs) have been increasingly recognized from clinical
      isolates worldwide, but the laboratory detection of these strains is not well
      defined. We report a study that developed an EDTA disk screen test and a
      molecular diagnostic assay for the detection of MBL-producing Pseudomonas
      aeruginosa. Using NCCLS disk methodology, inhibition zone diameters were
      determined in tests with imipenem (IPM) and meropenem (MEM) disks alone and in
      combination with 930 microg of EDTA. This test was compared with the MBL Etest.
      The duplex PCR assay showed 100% sensitivity and specificity for detecting MBL
      producing control strains. Of the 241 clinical strains of IPM-nonsusceptible P.
      aeruginosa from the Calgary Health Region isolated from 2002 to 2004, 110/241
      (46%) were MBL positive using phenotypic methods while 107/241 (45%) were PCR
      positive for MBL genes: 103/241 (43%) for bla(VIM) and 4/241 (2%) for bla(IMP).
      The EDTA disk screen test using MEM showed 100% sensitivity and 97% specificity
      for detecting MBLs in control and clinical strains. The EDTA disk screen test is
      simple to perform and to interpret and can easily be introduced into the workflow
      of a clinical laboratory. We recommend that all IPM-nonsusceptible P. aeruginosa
      isolates be routinely screened for MBL production using the EDTA disk screen test
      and that PCR confirmation be performed at a regional laboratory.

PMID- 16000425
TI  - Real-time nucleic acid sequence-based amplification using molecular beacons for
      detection of enterovirus RNA in clinical specimens.
AB  - Real-time nucleic acid sequence-based amplification (NASBA) using molecular
      beacon technology (NASBA-beacon) was compared to standard NASBA with
      postamplification hybridization using electrochemiluminescently labeled probes
      (NASBA-ECL) for detection of enteroviruses (EV) in 133 cerebrospinal fluid and 27
      stool samples. NASBA-ECL and NASBA-beacon were similar in sensitivity, detecting
      55 (100%) and 52 (94.5%) EV-positive samples, respectively. There were no false
      positives. Both NASBA assays were significantly more sensitive than culture. Real
      time NASBA-beacon reagents and equipment rental were more expensive than those
      for NASBA-ECL; however, time to result was shortened by 1.5 h, hands-on time was
      reduced by 25 min, and the assay was much simpler for technologists to learn and
      perform.

PMID- 16000426
TI  - Genetic relatedness between pneumococcal populations originating from the
      nasopharynx, adenoid, and tympanic cavity of children with otitis media.
AB  - Previous studies have shown that Streptococcus pneumoniae exists in both middle
      ear effusions and the upper respiratory region from children with otitis media
      with effusion (OME), but it remains unclear whether these strains represent
      genetically identical clones. Therefore, it cannot be determined whether these
      bacteria originate from a common source. To determine the presence of pneumococci
      at different anatomical locations of OME patients, conventional culture and PCR
      techniques were used. To analyze the possible genetic relatedness between
      pneumococci from different anatomical sites, molecular typing by amplified
      fragment length polymorphism was utilized. The percentage of middle ear effusions
      of OME patients that are positive for pneumococci after PCR analysis (13%) was
      higher than after conventional culture (5%). Molecular fingerprints from
      pneumococci derived from two different anatomic sites within patients were very
      similar in 80% of OME patients and in 90% of acute otitis medium patients,
      indicating their genetic relatedness. Biofilm formation or pneumococcal L-forms
      probably play a role in OME, since culture-negative effusions prove to contain
      pneumococcal DNA. Bacteria involved in this process most likely originate from
      the nasopharynx since they show a close genetic relatedness with their
      nasopharyngeal counterparts.

PMID- 16000427
TI  - Applicability of oral fluid collected onto filter paper for detection and genetic
      characterization of measles virus strains.
AB  - Expansion of measles molecular surveillance to developing countries where measles
      is endemic will help facilitate measles control. Limited infrastructure in these
      areas is a barrier to referral of specimens suitable for measles virus (MV)
      genotyping. In this study, we demonstrate that oral fluid dried onto filter paper
      can be used for the detection and characterization of MV strains. Using this
      approach, an MV-positive sample by reverse transcriptase PCR could be obtained
      from 67% of serologically confirmed acute measles cases. Mimicking certain
      environmental conditions and duration of transportation established that MV RNA
      remained detectable and suitable for nucleic acid sequencing in oral fluid spots
      for at least 1 week. In the context of a measles outbreak in a remote region of
      the world where infrastructure is poor, oral fluid samples dried onto filter
      paper and sent to a specialized laboratory for testing will aid in the
      identification and characterization of the causative MV strain.

PMID- 16000428
TI  - Clinical and prognostic importance of serotyping Mycobacterium avium
      Mycobacterium intracellulare complex isolates in human immunodeficiency virus
      negative patients.
AB  - We studied whether the serotypes of Mycobacterium avium-Mycobacterium
      intracellulare complex (MAC) isolates determine the prognosis for pulmonary MAC
      disease. We prospectively monitored a cohort of 68 patients with pulmonary MAC
      disease for whom the serotype-specific glycopeptidolipids in isolates were
      identified using thin-layer chromatography and fast atom bombardment mass
      spectrometry in 1990 and 1995. Serovar 4 Mycobacterium avium was detected in
      40/68 patients (58.8%). Other serotypes were serotypes 1 (five cases), 6 (three
      cases), 8 (seven cases), 9 (three cases), 14 (four cases), and 16 (six cases).
      Patients with serovar 4 were significantly (P < 0.01) younger (63.0 +/- 9.8
      years) than patients with other serotypes (71.8 +/- 10.3). Patients who failed
      treatment had a significantly poorer prognosis than other patients. There were no
      cases of MAC-related death in the cured group. Chest radiographic findings
      progressively worsened in 36 (90%) of patients with serotype 4, and 14/36 died
      from respiratory failure caused by pulmonary Mycobacterium avium disease. The
      patients with serotype 4 had a significantly poorer prognosis than patients with
      other serotypes. These results show that both the outcome of chemotherapy and the
      serotypes of MAC isolates are important for assessing the prognosis of pulmonary
      MAC disease.

PMID- 16000429
TI  - Drug susceptibility testing of Mycobacterium tuberculosis by a nitrate reductase
      assay applied directly on microscopy-positive sputum samples.
AB  - Current methods for drug susceptibility testing of Mycobacterium tuberculosis are
      either costly or slow. As the prevalence of multidrug-resistant strains
      increases, the need for fast, reliable, and inexpensive methods that can also be
      applied in settings with scarce resources is obvious. We evaluated a rapid
      colorimetric nitrate reductase assay (NRA) for direct drug susceptibility testing
      of M. tuberculosis directly from clinical sputum samples with positive microscopy
      results for acid-fast bacilli with more than 10 acid-fast bacilli per high-power
      field. We have saved valuable time by omitting the preisolation step. The
      sensitivity (ability to detect true drug resistance) and specificity (ability to
      detect true drug susceptibility) of the direct NRA, using the direct proportion
      method as the reference, were 100 and 100%, 93 and 100%, 76 and 100%, and 55 and
      99% for rifampin, isoniazid, streptomycin, and ethambutol, respectively, when
      tested on M. tuberculosis strains present in 121 samples. The results were in
      most cases available in 14 days. The direct NRA could be used as a rapid,
      inexpensive, and accurate method to determine rifampin and isoniazid
      susceptibility directly from sputum. The technique might become a valid
      alternative to traditional methods, especially in low-income countries.

PMID- 16000430
TI  - Susceptibility of Neisseria meningitidis to 16 antimicrobial agents and
      characterization of resistance mechanisms affecting some agents.
AB  - Neisseria meningitidis represents a pathogen of great public health importance in
      both developed and developing countries. Resistance to some antimicrobial agents
      used either for therapy of invasive infections or for prophylaxis of case
      contacts has long been recognized, although specific guidelines for
      susceptibility testing have not been fully developed. We have examined the
      susceptibilities of a collection of 442 meningococcal clinical isolates from 15
      countries to 16 antimicrobial agents. These included isolates recovered between
      1917 and 2004, with representatives of all major serogroups. All isolates were
      tested by the Clinical and Laboratory Standards Institute (formerly NCCLS) broth
      microdilution method using Mueller-Hinton lysed horse blood broth, while a subset
      of 102 isolates was tested by agar dilution using Mueller-Hinton sheep blood
      agar. Most isolates provided adequate growth for MIC determinations by both broth
      and agar methods. Growth in broth was enhanced by CO(2) incubation and was
      required for two strains (1.7%). MICs of the study drugs compared favorably
      between the broth and agar methods (79 to 100% essential agreement), and MICs
      also generally agreed closely (92 to 100% essential agreement, excluding
      azithromycin) between broth tests incubated in the two different atmospheres.
      Elevated penicillin and ampicillin MICs (> or =0.12 microg/ml and > or =0.25
      microg/ml, respectively) occurred in 14.3% and 8.6% of strains and were
      associated with polymorphisms of the penA gene encoding a modified penicillin
      binding protein 2. None of the 442 isolates produced beta-lactamase. Elevated
      tetracycline and doxycycline (but not minocycline) MICs were associated with
      efflux-mediated resistance encoded by tet(B) in 13 strains. Resistance to
      sulfisoxazole in 21.7% of strains and to trimethoprim-sulfamethoxazole in 21.0%
      resulted from polymorphisms of folP encoding a modified dihydropteroate
      synthetase. Seven strains were resistant to rifampin due to mutations in the rpoB
      gene, and two strains were resistant to chloramphenicol due to production of
      chloramphenicol acetyltransferase mediated by catP. Two strains had reduced
      quinolone susceptibility due to mutations of gyrA. The determination of the
      susceptibilities of a large group of meningococcal strains (including strains
      with characterized resistance mechanisms) to 16 antimicrobial agents has served
      as the essential first step in defining susceptibility testing breakpoints
      specific for this organism.

PMID- 16000431
TI  - Purification and characterization of Nipah virus nucleocapsid protein produced in
      insect cells.
AB  - The nucleocapsid (N) protein of Nipah virus (NiV) is a major constituent of the
      viral proteins which play a role in encapsidation, regulating the transcription
      and replication of the viral genome. To investigate the use of a fusion system to
      aid the purification of the recombinant N protein for structural studies and
      potential use as a diagnostic reagent, the NiV N gene was cloned into the
      pFastBacHT vector and the His-tagged fusion protein was expressed in Sf9 insect
      cells by recombinant baculovirus. Western blot analysis of the recombinant fusion
      protein with anti-NiV antibodies produced a band of approximately 62 kDa. A time
      course study showed that the highest level of expression was achieved after 3
      days of incubation. Electron microscopic analysis of the NiV recombinant N fusion
      protein purified on a nickel-nitrilotriacetic acid resin column revealed
      different types of structures, including spherical, ring-like, and herringbone
      like particles. The light-scattering measurements of the recombinant N protein
      also confirmed the polydispersity of the sample with hyrdrodynamic radii of small
      and large types. The optical density spectra of the purified recombinant fusion
      protein revealed a high A(260)/A(280) ratio, indicating the presence of nucleic
      acids. Western blotting and enzyme-linked immunosorbent assay results showed that
      the recombinant N protein exhibited the antigenic sites and conformation
      necessary for specific antigen-antibody recognition.

PMID- 16000432
TI  - Cysticercosis immunodiagnosis using 18- and 14-kilodalton proteins from Taenia
      crassiceps cysticercus antigens obtained by immunoaffinity chromatography.
AB  - Monoclonal antibodies (MAb) against Taenia crassiceps and Taenia solium
      cysticerci were produced and showed cross-reactivity with a 14-kDa protein from
      T. solium and with 18- and 14-kDa proteins from T. crassiceps. These MAbs and
      antibodies from cerebrospinal fluid (CSF) as well as serum samples from patients
      with neurocysticercosis (NC) reacted with 18- and 14-kDa T. crassiceps proteins
      purified by immunoaffinity chromatography using a Sepharose column coupled with
      MAbs (anti-excretory/secretory or anti-vesicular fluid antigens). Immunoaffinity
      purified 18- and 14-kDa proteins were used in the design of a diagnostic enzyme
      linked immunosorbent assay (ELISA) to detect antibodies in 23 CSF and 20 serum
      samples from patients with NC, showing 100% sensitivity. The test specificity was
      determined using 42 noninflammatory CSF samples and 70 inflammatory CSF samples
      from patients with other neurological disorders (OND), showing 100% and 99.1%
      (confidence interval, 97.3% to 100%) specificity, respectively. A false-positive
      CSF sample result in the OND group was from a human immunodeficiency virus
      positive patient with meningoencephalitis. By using serum samples from 194
      healthy individuals, the specificity was 100%. Analysis of an additional 16 serum
      samples from individuals with other parasitic diseases (13 with intestinal
      parasitosis and 3 with schistosomiasis) showed negative results. Three (10%)
      serum samples from patients with hydatidosis were positive in our ELISA and in
      ELISA with T. solium cysticerci antigens. Two of them were also positive by
      immunoblotting. The use of 18- and 14-kDa T. crassiceps immunoaffinity-purified
      proteins for detection of anti-cysticercus antibodies in CSF and/or serum samples
      using an ELISA system showed a good performance and high specificity for serum
      samples, dispensing with the use of confirmatory tests, such as immunoblotting,
      for checking specificity.

PMID- 16000434
TI  - Detection of Balamuthia mitochondrial 16S rRNA gene DNA in clinical specimens by
      PCR.
AB  - Balamuthia mandrillaris is a free-living ameba that causes granulomatous amebic
      encephalitis in both immunocompromised and immunocompetent individuals. Because
      of a lack of pathognomonic symptoms and the difficulty in recognizing amebas in
      biopsied tissues, most cases are not diagnosed or effectively treated, leading to
      a >95% mortality. We report here on five cases of balamuthiasis that were
      diagnosed by indirect immunofluorescence (IIF) staining of serum for anti
      Balamuthia antibodies (titer > or = 1:128) and confirmed by IIF of unstained
      brain tissue sections and/or detection of amebas in hematoxylin-eosin-stained
      slides. Additionally, we have used the PCR for the detection of mitochondrial 16S
      rRNA gene DNA from the ameba in clinical specimens such as brain tissue and
      cerebrospinal fluid (CSF) from individuals with Balamuthia encephalitis.
      Balamuthia DNA was successfully detected by the PCR in clinical samples from all
      five individuals. It was detected in brain tissue from three cases, in CSF from
      three cases, and in one of two samples of lung tissue from two individuals, but
      not in two samples of kidney tissue tested. One sample of unfixed brain tissue
      was culture positive for Balamuthia. In order to test the sensitivity of the PCR
      for detection of Balamuthia DNA, CSF specimens from two individuals negative for
      amebic infection were spiked with Balamuthia amebas. We found that it was
      possible to detect Balamuthia DNA in the PCR mixtures containing mitochondrial
      DNA from 1 to as little as 0.2 ameba per reaction mixture. A single Balamuthia
      ameba contains multiple mitochondrial targets; thus, 0.2 ameba represents
      multiple targets for amplification and is not equivalent to 0.2 of an ameba as a
      target.

PMID- 16000433
TI  - Genomic deletions classify the Beijing/W strains as a distinct genetic lineage of
      Mycobacterium tuberculosis.
AB  - Beijing/W strains of Mycobacterium tuberculosis are geographically widespread and
      hypervirulent. To enhance our understanding of their origin and evolution, we
      sought phylogenetically informative large sequence polymorphisms (LSPs) within
      the Beijing/W family. Comparative whole-genome hybridization of Beijing/W strains
      revealed 21 LSPs, 7 of which were previously unreported. We show that some of
      these LSPs are unique event polymorphisms that can be used to define and
      subdivide the Beijing/W family. One LSP (RD105) was seen in all Beijing/W strains
      and thus serves as a useful marker for the identification of this family of
      strains. Additional LSPs (RD142, RD150, and RD181) further divided this family
      into four monophyletic subgroups, demonstrating a deeper population structure
      than previously appreciated. All Beijing/W strains were also observed to have an
      intact pks15/1 gene that is involved in the biosynthesis of a phenolic
      glycolipid, a putative virulence factor. A simple PCR assay using these Beijing/W
      strain-defining deletions will facilitate molecular epidemiological studies and
      may assist in the identification of the molecular basis of phenotypes associated
      with this important lineage of M. tuberculosis.

PMID- 16000435
TI  - Genotyping of methicillin-resistant Staphylococcus aureus strains from two
      hospitals in Bangalore, South India.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen
      in India, and up to 70% methicillin resistance has been reported from hospitals
      in various parts of India. Hospitals use phenotyping for the most part, and
      molecular genotyping is not done. Here we report on the genotyping of 82 single
      patient isolates from two hospitals in Bangalore, South India, for the first
      time. Most of the strains possessed type III or IIIA staphylococcal cassette
      chromosome (SCCmec) cassettes, and we did not detect strains with type I, IA, or
      II cassettes. Most isolates also contained the type III cassette chromosome
      recombinase (ccr) AB region. Multilocus sequence typing (MLST) and staphylococcal
      protein A (spa) typing of a selected number of isolates have been carried out.
      Although most isolates that were chosen for MLST and spa typing had the same
      patterns, they were quite diverse in their pulsed-field gel electrophoresis
      (PFGE) patterns. PFGE, MLST, and spa typing of the Indian strains revealed that
      they are related to the previously described Hungarian and Brazilian clones.

PMID- 16000436
TI  - Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus
      isolates from surgically drained abscesses.
AB  - Between 1 February and 15 April 2002, 95 patients were admitted to Gaston Bourret
      Territorial Hospital (New Caledonia, France) for drainage of community-acquired
      soft tissue abscesses. Staphylococcus aureus was detected in 68 cases (72%). Two
      thirds of the patients with S. aureus infection had furuncles, which were located
      on the limbs in 82% of cases. The median interval between symptom onset and
      hospital admission was 5.7 days. Three-quarters of the patients were Melanesians
      living in tribes. Fifty-four S. aureus isolates were screened for toxin genes.
      Panton-Valentine leucocidin (PVL) genes were detected in 48 isolates (89%), the
      exfoliative toxin A gene was detected in 1 isolate, and no toxin genes were
      detected in 4 isolates. S. aureus nasal carriage was detected in 39.7% of
      patients with S. aureus infections. Two infecting S. aureus strains and two nasal
      carriage strains were resistant to methicillin. Comparative pulsed-field gel
      electrophoresis, performed in 16 cases, showed that five of six patients with PVL
      positive nasal carriage strains were infected by the same strains. In contrast, 8
      of 10 patients with PVL-negative nasal carriage strains were infected by PVL
      positive strains. PVL genes thus appear to be a major virulence factor in both
      primary and secondary S. aureus skin infections.

PMID- 16000437
TI  - Characterization of a novel P[25],G11 human group a rotavirus.
AB  - A novel rotavirus strain (Dhaka6) isolated from a 21-year-old Bangladeshi male
      patient was characterized by sequence analysis of its VP7 and VP4 gene segments.
      Phylogenetic analysis of the VP7 gene of the Dhaka6 strain revealed a common
      evolutionary lineage with porcine G11 rotavirus strains. This isolate is the
      first reported G11 rotavirus strain infecting a human host. Comparison of the VP4
      gene sequences with all currently recognized 24 different P genotypes revealed
      only low nucleotide (54 to 71%) and amino acid (52 to 76%) sequence identities.
      This lack of high sequence similarity in the VP4 gene indicates that the Dhaka6
      isolate represents a new group A rotavirus P genotype, to which we propose
      assignment of the designation P[25].

PMID- 16000438
TI  - Characterization of a shiga toxin-, intimin-, and enterotoxin hemolysin-producing
      Escherichia coli ONT:H25 strain commonly isolated from healthy cattle.
AB  - Among bovine fecal and recto-anal mucosal swab samples cultured in our laboratory
      for Escherichia coli O157:H7, we frequently isolated E. coli organisms that were
      phenotypically similar to the O157:H7 serotype as non-sorbitol fermenting and
      negative for beta-glucuronidase activity but serotyped O nontypeable:H25
      (ONT:H25). This study determined the prevalence and virulence properties of the
      E. coli ONT:H25 isolates. Among dairy and feedlot cattle (n = 170) sampled in
      Washington, Idaho, and Alberta, Canada, the percentage of animals culture
      positive for E. coli ONT:H25 ranged from 7.5% to 22.5%, compared to the
      prevalence of E. coli O157:H7 that ranged from 0% to 15%. A longitudinal 8-month
      study of dairy heifers (n = 40) showed that 0 to 15% of the heifers were culture
      positive for E. coli O157:H7, while 15 to 22.5% of the animals were culture
      positive for E. coli ONT:H25. As determined by a multiplex PCR, the E. coli
      ONT:H25 isolates carried a combination of virulence genes characteristic of the
      enterohemorrhagic E. coli, including intimin, translocated intimin receptor,
      Stx2, and hemolysin (eae-beta, tir, stx(2vh-a), and hly). E. coli ONT:H25
      isolates from diverse geographic locations and over time were fingerprinted by
      separating XbaI-restricted chromosomal DNA by pulsed-field gel electrophoresis
      (PFGE) separation. Two strains of E. coli ONT:H25 were highly similar by PFGE
      pattern. Experimental inoculation of cattle showed that E. coli ONT:H25, like E.
      coli O157:H7, colonized the bovine recto-anal junction mucosa for more than 4
      weeks following a single rectal application of bacteria.

PMID- 16000439
TI  - Quantitative PCR assay using sputum samples for rapid diagnosis of pneumococcal
      pneumonia in adult emergency department patients.
AB  - Accurate diagnosis of pneumococcal pneumonia in the acute-care setting remains a
      challenge due to the inadequate sensitivity of conventional diagnostic tests.
      Sputum cultures, which are likely to have the highest diagnostic yields of all
      specimen types, have been considered unreliable, due to their inability to
      differentiate colonization from infection. Our objective was to evaluate the
      potential clinical utility of a rapid quantitative real-time PCR assay using
      sputum samples for Streptococcus pneumoniae in adult patients with community
      acquired pneumonia (CAP). A prospective clinical observational study of
      consecutively enrolled emergency department patients with CAP was performed; only
      those patients with excess good-quality sputum samples were included for
      evaluation. Sputum samples were tested for the presence of S. pneumoniae by using
      a quantitative PCR that targets the pneumolysin gene. PCR findings were compared
      with those of a composite reference standard comprising Gram staining of sputum
      samples and sputum/blood cultures. The area under the curve (AUC) and a log
      transformed threshold, which provides the maximal sensitivity and specificity,
      were calculated. Of 487 subjects enrolled, 129 were evaluable. Receiver operating
      characteristic curve analysis demonstrated an AUC of 0.87. Sensitivity and
      specificity were 90.0 percent and 80.0 percent, respectively; positive and
      negative predictive values were 58.7 percent and 96.2 percent, respectively. We
      have demonstrated that a quantitative rapid pneumolysin PCR assay has favorable
      accuracy for diagnosis of pneumococcal pneumonia in adult patients with CAP; this
      assay may be a useful diagnostic adjunct for clinicians, particularly those
      practicing in the acute-care setting, where rapid pathogen identification may
      assist in selection of the most appropriate antibiotics.

PMID- 16000440
TI  - Comparative analysis of immunoglobulin M (IgM) capture enzyme-linked
      immunosorbent assay using virus-like particles or virus-infected mouse brain
      antigens to detect IgM antibody in sera from patients with evident flaviviral
      infections.
AB  - The use of immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent
      assay (MAC-ELISA) serves as a valuable tool for the diagnosis of acute flaviviral
      infections, since IgM antibody titers are detectable early, peak at about 2 weeks
      postinfection, and subsequently decline to lower levels over the next few months.
      Traditionally, virus-infected tissue culture or suckling mouse brain (SMB) has
      been the source of viral antigens used in the assay. In an effort to provide a
      reliable source of standardized viral antigens for serodiagnosis of the medically
      important flaviviruses, we have developed a eukaryotic plasmid vector to express
      the premembrane/membrane and envelope proteins which self-assemble into
      noninfectious virus-like particles (VLPs). In addition to the plasmids for
      Japanese encephalitis virus, West Nile virus (WNV), St. Louis encephalitis virus
      (SLEV), and dengue virus type 2 (DENV-2) reported earlier, we recently
      constructed the DENV-1, -3, and -4 VLP expression plasmids. Three blind-coded
      human serum panels were assembled from patients having recent DENV, SLEV, and WNV
      infections to assess the sensitivity and specificity of the MAC-ELISA using VLPs
      or SMB antigens. In addition, serum specimens from patients infected with either
      Powassan virus or La Crosse encephalitis virus were used to evaluate the cross
      reactivity of seven mosquito-borne viral antigens. The results of the present
      studies showed higher sensitivity when using SLEV and WNV VLPs and higher
      specificity when using SLEV, WNV, and the mixture of DENV-1 to -4 VLPs in the MAC
      ELISA than when using corresponding SMB antigens. Receiver operating
      characteristic (ROC) curve analysis, a plot of the sensitivity versus false
      positive rate (100 - specificity), was applied to discriminate the accuracy of
      tests comparing the use of VLPs and SMB antigen. The measurement of assay
      performance by the ROC analysis indicated that there were statistically
      significant differences in assay performance between DENV and WNV VLPs and the
      respective SMB antigens. Additionally, VLPs had a lower cutoff positive/negative
      ratio than corresponding SMB antigens when employed for the confirmation of
      current infections. The VLPs also performed better than SMB antigens in the MAC
      ELISA, as indicated by a higher positive prediction value and positive likelihood
      ratio test. Cell lines continuously secreting these VLPs are therefore a
      significantly improved source of serodiagnostic antigens compared to the
      traditional sources of virus-infected tissue culture or suckling mouse brain.

PMID- 16000441
TI  - Ceftriaxone resistance of nontyphoidal Salmonella enterica isolates in Northern
      Taiwan attributable to production of CTX-M-14 and CMY-2 beta-lactamases.
AB  - Among 3,027 nontyphoidal Salmonella enterica isolates identified between January
      1999 and December 2002 in a medical center in northern Taiwan, 31 were resistant
      to the extended-spectrum cephalosporin ceftriaxone (1.02% [31/3,027]), including
      2 in 1999 (0.36% [2/549]), 13 in 2000 (1.49% [13/870]), 7 in 2001 (0.78%
      [7/893]), and 9 in 2002 (1.26% [9/715]). Sixteen of these isolates belonged to
      Salmonella serogroup B, nine belonged to serogroup C, four belonged to serogroup
      D, and two belonged to serogroup E. The majority were from stool cultures. The
      mechanism of resistance was investigated for eight isolates, including three S.
      enterica serovar Typhimurium, one S. enterica serovar Wagenia, one S. enterica
      serovar Senftenberg, one S. enterica serovar Derby, one S. enterica serovar
      Panama, and one S. enterica serovar Duesseldorf isolate. All eight patients from
      whom these isolates were recovered had community-acquired infections. All eight
      isolates were resistant to ampicillin, ceftriaxone, and cefotaxime but
      susceptible to imipenem and ciprofloxacin. Ceftriaxone resistance was due to the
      production of the CMY-2 AmpC beta-lactamase by seven isolates and the CTX-M-14
      beta-lactamase by the remaining isolate. Both beta-lactamase genes were carried
      on conjugative plasmids. In a 2.5-kb region encompassing the bla(CMY-2) gene, at
      nucleotide 49 upstream of the start codon of bla(CMY-2), three of the seven
      bla(CMY-2)-positive isolates had an A nucleotide and four had a G nucleotide. In
      conclusion, the ceftriaxone resistance of nontyphoidal Salmonella isolates in our
      hospital was attributed to the CTX-M-14 and CMY-2 beta-lactamases.

PMID- 16000442
TI  - Comparative recovery of microorganisms from BacT/ALERT plastic and glass FA and
      FN blood culture bottles.
AB  - bioMerieux, Inc., has recently introduced plastic bottles to replace glass
      bottles for use in the BacT/ALERT blood culture system. We compared the
      performance of the plastic to the glass bottles in a large clinical evaluation.
      Two blood cultures were collected from each patient, one using glass FA (aerobic)
      and FN (anaerobic) bottles and one using plastic FA and FN bottles. Of the 4,040
      sets of four bottles collected, 3,110 contained the recommended 8 to 12 ml of
      blood, yielding 524 microorganisms with 359 judged to be clinically significant.
      Of the 359 significant organisms, 255 were recovered in either one or two bottles
      from both pairs of bottles in a set while 56 organisms were recovered only from
      the glass bottles and 48 were recovered only from the plastic bottles (P, not
      significant [NS]). Of the 286 significant organisms recovered only in the FA
      bottles (glass and plastic), 180 were recovered in both bottles, 57 in the
      plastic bottles only, and 49 in the glass bottles only (P, NS). Of the 303
      significant organisms recovered in the FN bottles only (glass and plastic), 212
      were recovered in both bottles, 46 in the plastic bottles only, and 45 in the
      glass bottles only (P, NS). For individual organisms, the only significant
      difference in recovery was obtained for Escherichia coli, with more isolates
      recovered in the FN plastic than in the FN glass bottles (P = 0.02). These data
      suggest that recovery of microorganisms with plastic FA/FN bottles is at least
      equal to that with glass FA/FN bottles while offering greater safety for users.

PMID- 16000443
TI  - Development and evaluation of Chlamylege, a new commercial test allowing
      simultaneous detection and identification of Legionella, Chlamydophila
      pneumoniae, and Mycoplasma pneumoniae in clinical respiratory specimens by
      multiplex PCR.
AB  - This study describes the development and evaluation of a new commercial test,
      Chlamylege (Argene Inc.), which allows the simultaneous detection in respiratory
      samples of Chlamydophila pneumoniae, Mycoplasma pneumoniae, and most Legionella
      species, as well as PCR inhibitors, by using a multiplex PCR and microplate
      hybridization. The sensitivities of Chlamylege were 1 x 10(-3) IFU, 5 x 10(-2)
      color-changing units, and 1 CFU per reaction tube for C. pneumoniae, M.
      pneumoniae, and Legionella pneumophila, respectively. A cohort of 154 clinical
      samples from patients with documented respiratory infections was analyzed by the
      kit, including 2 samples from patients with C. pneumoniae infection, 9 samples
      from patients with M. pneumoniae infection, 19 samples from patients with
      Legionella species infection, and 114 samples that tested negative for the three
      pathogens. All the positive specimens were correctly detected and identified by
      the Chlamylege kit, and no false-positive result was observed with the negative
      samples. The kit was then evaluated in a pediatric prospective study that
      included 220 endotracheal aspirates, and the results were compared with those
      obtained by three single in-house PCR assays. Four specimens were found to be
      positive for C. pneumoniae and six were found to be positive for M. pneumoniae by
      using both strategies. The Chlamylege kit detected two additional samples
      positive for M. pneumoniae and one additional sample positive for a Legionella
      species other than L. pneumophila; these three samples were shown to be true
      positive by other techniques. These overall results demonstrate that the
      Chlamylege assay is sensitive, specific, and convenient for the rapid detection
      and identification of atypical pathogens in clinical samples from patients with
      respiratory infections.

PMID- 16000444
TI  - Suspension microarray with dendrimer signal amplification allows direct and high
      throughput subtyping of Listeria monocytogenes from genomic DNA.
AB  - Listeria monocytogenes is a significant cause of food-borne disease and
      mortality; therefore, epidemiological investigations of this pathogen require
      subtyping methods that are rapid, discriminatory, and reproducible. Although
      conventional microarray subtyping analysis has been shown to be both high
      resolution and genetically informative, it is still relatively low throughput and
      technically challenging. Suspension microarray technology eliminates the
      technical issues associated with planar microarrays and allows high-throughput
      subtyping of L. monocytogenes strains. In this study, a suspension array assay
      using dendrimer signal amplification allowed rapid and accurate serovar
      identification of L. monocytogenes strains using genomic DNA as a target. The
      ability to subtype genomic DNA without PCR amplification allows probes to be
      designed for many different regions within the bacterial genome and should allow
      high-resolution subtyping not possible with multiplex PCR.

PMID- 16000445
TI  - Comparison between the Hybrid Capture II test and a PCR-based human
      papillomavirus detection method for diagnosis and posttreatment follow-up of
      cervical intraepithelial neoplasia.
AB  - Human papillomavirus (HPV) infection is the major cause of cervical cancer and
      its precursor, cervical intraepithelial neoplasia (CIN), and HPV testing has
      therefore been proposed for improved triaging and follow-up of women treated for
      CIN. We compared two common HPV DNA detection tests (Hybrid Capture II [HCII] and
      PCR-enzyme immunosorbent assay (EIA) using the primers GP5+/GP6+ followed by HPV
      typing with reverse dot blot hybridization) for sensitivity and specificity for
      detection of CIN and of CIN recurrence after treatment. Two hundred and thirty
      nine women referred to the Department of Obstetrics and Gynaecology in Vasteras,
      Sweden, were enrolled because of atypical Pap smears; 177 of these were later
      treated for dysplasia by conization or loop diathermy. Samples for HPV DNA
      testing were taken before and 4 to 6 months after treatment. There was
      substantial agreement between the HCII and PCR-EIA (kappa, 0.70 before treatment
      and 0.72 after treatment). The sensitivity for histopathologically confirmed CIN
      III was 100.0% for PCR-EIA and 95.6% for HCII. For patients with CIN II or worse
      (CIN II+), the sensitivities were 92.9% (PCR-EIA) and 91.8% (HCII). The
      specificities for CIN II+ in the pretreatment setting were 30.4% for PCR-EIA and
      24.1% for HCII. After treatment, the sensitivities for CIN III in cytology were
      100.0% by both methods, and for CIN II+, sensitivities were 80.0% by both
      methods. The specificities for CIN II+ in the posttreatment setting were 83.5%
      for PCR and 85.4% for HCII. In conclusion, the sensitivities of both PCR-EIA and
      HCII are high and almost equal, suggesting that both methods are suitable as
      tools for detection and posttreatment follow-up of CIN II-III.

PMID- 16000446
TI  - Flow cytometry-based assay for titrating dengue virus.
AB  - Plaque assays for titrating dengue virus (DENV) are time-consuming and not
      suitable for strains that do not plaque. Fluorescence-activated cell sorting
      (FACS) has been used to detect DENV-infected cells. Here we describe a FACS-based
      assay for titrating DENV. We determined that at 24 h postinfection, the number of
      infected cells detected by FACS represented the first round of infection and
      therefore could be used as a readout of the number of infectious particles in the
      inoculum. When the titers of different laboratory and clinical strains of DENV
      were compared using FACS, plaque, and endpoint dilution assays, for most strains
      the FACS titers were comparable to titers obtained by plaque or endpoint dilution
      assays. The FACS assay is an improvement over the plaque assay because the
      infection period is reduced from 5 to 7 days to 24 h and the assay can be used to
      titrate clinical isolates that frequently do not form clear plaques on cell
      monolayers. The novel FACS-based methods described here will facilitate
      laboratory studies of dengue.

PMID- 16000447
TI  - Extended-spectrum-beta-lactamase-producing Enterobacteriaceae in Yaounde,
      Cameroon.
AB  - Organisms producing extended-spectrum beta-lactamases (ESBLs) have been reported
      in many countries, but there is no information on the prevalence of ESBL
      producing members of the family Enterobacteriaceae in Cameroon. A total of 259
      Enterobacteriaceae strains were isolated between 1995 and 1998 from patients at
      the Yaounde Central Hospital in Cameroon. Enterobacterial isolates resistant to
      extended-spectrum cephalosporin and monobactam were screened for ESBL production
      by the double-disk (DD) synergy test. Thirty-one (12%) of these
      Enterobacteriaceae strains were shown to be positive by the DD synergy test,
      suggesting the presence of ESBLs. Resistance to oxyimino-cephalosporins and
      monobactams of 12 (38.7%) of the 31 strains-i.e., 6 Klebsiella pneumoniae, 4
      Escherichia coli, 1 Citrobacter freundii, and 1 Enterobacter cloacae strain-was
      transferred to E. coli HK-225 by conjugation. Resistance to gentamicin,
      gentamicin plus trimethoprim-sulfamethoxazole, or trimethoprim-sulfamethoxazole
      was cotransferred into 6, 2, and 1 of these transconjugants, respectively. All 12
      transconjugants were resistant to amoxicillin, piperacillin, all of the
      cephalosporins, and aztreonam but remained susceptible to cefoxitin and imipenem.
      Crude extracts of beta-lactamase-producing transconjugants were able to reduce
      the diameters of inhibition zones around disks containing penicillins, narrow- to
      expanded-spectrum cephalosporins or monobactams when tested against a fully
      susceptible E. coli strain but had no effect on such zones around cefoxitin,
      imipenem, and amoxicillin-clavulanate disks. The beta-lactamases produced by the
      12 tranconjugants turned out to be SHV-12 by DNA sequencing. Therefore, the ESBL
      SHV-12 is described for the first time in Cameroon.

PMID- 16000448
TI  - Comparative assessment of the gelatin particle agglutination test and an enzyme
      linked immunosorbent assay for diagnosis of strongyloidiasis.
AB  - The performances of the gelatin particle agglutination test (GPAT) and enzyme
      linked immunosorbent assay (ELISA) for the diagnosis of strongyloidiasis with
      reference to the results of the agar plate culture technique (APCT) were
      evaluated with samples from 459 individuals from communities in northeast
      Thailand where strongyloidiasis is endemic. The prevalence of strongyloidiasis in
      five sample groups determined by GPAT varied between 29.3 and 61.5% (mean,
      38.8%). ELISA and APCT, employed concurrently, gave lower prevalence rates of
      27.5% (range, 21.6 to 42.1%) and 22.7% (range, 12.7 to 53.8%), respectively. By
      using APCT as the standard method, the sensitivity of GPAT was generally higher
      than that of ELISA (81 versus 73%). The specificity of GPAT was slightly lower
      than that of ELISA (74 versus 86%). The resulting GPAT titers exhibited positive
      linear relationships with the ELISA values (optical density at 490 nm) (P <
      0.05), which suggests that the GPAT titer also reflects the levels of specific
      antibody comparable to those reflected by the ELISA values. Based on the relative
      ease and simplicity of use of the technique as well as the acceptable rates of
      sensitivity and specificity of the test, GPAT is more practical for screening for
      strongyloidiasis than the conventional ELISA.

PMID- 16000449
TI  - Characterization of vancomycin-resistant Enterococcus faecium isolates from
      broiler poultry and pig farms in England and Wales.
AB  - This study aimed to investigate the occurrence and molecular epidemiology of
      vancomycin-resistant Enterococcus faecium (VREF) isolates on poultry and pig
      farms in England and Wales. A total of 217 VREF isolates were obtained from fresh
      feces and environmental swabs collected from conventional and organic farms. A
      predominant pulsed-field gel electrophoresis (PFGE) profile was found for each
      VREF-positive farm, together with less frequent types. All isolates presented the
      vanA genotype and were esp negative. Seventy-six percent of the VREF isolates
      were additionally resistant to nine or more antimicrobials, presenting a diverse
      range of resistance phenotypes. The multiresistance traits did not appear to be
      specific to individual farms or sample types (i.e., environmental or fecal), nor
      did they correlate with any specific PFGE type. Ninety-three percent of the
      isolates were resistant to penicillin, 89% were resistant to tetracycline, 87.5%
      were resistant to erythromycin, and 50% were resistant to quinupristin
      dalfospristin (Synercid). The lack of clonality among these populations may
      suggest the horizontal transfer of resistance genes and/or a dynamic replacement
      of clonal lines rather than persistence.

PMID- 16000450
TI  - Sensitive and rapid detection of herpes simplex virus and varicella-zoster virus
      DNA by loop-mediated isothermal amplification.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid
      amplification method in which reagents react rapidly and efficiently, with a high
      specificity, under isothermal conditions. We used a LAMP assay for the detection
      of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and
      varicella-zoster virus (VZV). The virus specificities of primers were confirmed
      by using 50 HSV-1, 50 HSV-2, and 8 VZV strains. The assay was performed for 45
      min at 65 degrees C. The LAMP assay had a 10-fold higher sensitivity than a PCR
      assay. An analysis of nucleotide sequence variations in the target and primer
      regions used for the LAMP assay indicated that 3 of 50 HSV-1 strains had single
      nucleotide polymorphisms. No HSV-2 or VZV strains had nucleotide polymorphisms.
      Regardless of the sequence variation, there were no differences in sensitivity
      with the HSV-1-specific LAMP assay. To evaluate the application of the LAMP assay
      for clinical diagnosis, we tested clinical samples from 40 genital herpes
      patients and 20 ocular herpes patients. With the LAMP assay, 41 samples with DNA
      extraction and 26 direct samples without DNA extraction were identified as
      positive for HSV-1 or HSV-2, although 37 samples with DNA extraction and just one
      without DNA extraction were positive by a PCR assay. Thus, the LAMP assay was
      less influenced than the PCR assay by the presence of inhibitory substances in
      clinical samples. These observations indicate that the LAMP assay is very useful
      for the diagnosis of HSV-1, HSV-2, and VZV infections.

PMID- 16000451
TI  - Enterobacter hormaechei subsp. oharae subsp. nov., E. hormaechei subsp.
      hormaechei comb. nov., and E. hormaechei subsp. steigerwaltii subsp. nov., three
      new subspecies of clinical importance.
AB  - Six species and six additional genovars are combined within the so-called
      Enterobacter cloacae complex, with one of them being the species Enterobacter
      hormaechei. In a recent population genetic study, two genetic clusters were found
      in close phylogenetic proximity to the genetic cluster of E. hormaechei. In order
      to prove the hypothesis that these three genetic clusters belong to the same
      species, we performed cross-hybridization experiments in microplates with DNAs of
      representatives of each genetic cluster. The close phylogenetic relationship
      among the clusters was reflected by their relatively low deltaT(m) values,
      ranging from 0.3 to 4.8, confirming the hypothesis that the clusters are parts of
      the same species. These clusters can be distinguished from the other species of
      the E. cloacae complex, which have deltaT(m) values of 5.6 to 10.3. Forty-eight
      E. hormaechei strains from the different genetic clusters were phenotypically
      characterized with 129 biochemical tests. In this way, E. hormaechei could be
      differentiated from the other species of the E. cloacae complex because it tests
      negative in the 3-hydroxy-butyrate test. The three genetic clusters of E.
      hormaechei could also be differentiated from each other by using phenotypic
      tests. Hence, we propose three new subspecies of E. hormaechei corresponding to
      genetic clusters VI, VII, and VIII of the E. cloacae complex. E. hormaechei
      subsp. hormaechei comb. nov. corresponds to the original species description, as
      it gives negative results for the adonitol, d-arabitol, d-sorbitol, and d
      melibiose tests and a positive result for the dulcitol test. E. hormaechei subsp.
      oharae subsp. nov. gives negative results for the dulcitol, adonitol, and d
      arabitol tests and positive results for the d-sorbitol and d-melibiose tests. E.
      hormaechei subsp. steigerwaltii subsp. nov. gives a negative result for the
      dulcitol test and positive results for the adonitol, d-arabitol, d-sorbitol, and
      d-melibiose tests. Among the members of the E. cloacae complex, E. hormaechei
      seems to be the species most frequently recovered from clinical specimens.

PMID- 16000452
TI  - Use of a locked-nucleic-acid oligomer in the clamped-probe assay for detection of
      a minority Pfcrt K76T mutant population of Plasmodium falciparum.
AB  - Given the emergence of drug resistance and the high rate of polyclonal
      microorganism infections, the availability of a fast and sensitive test to detect
      minority mutant populations would be an improvement in the diagnosis of
      infectious diseases. A clamped-probe real-time PCR assay to diagnose the
      Plasmodium falciparum K76T mutation in clone populations was developed, using a
      wild-type-specific locked-nucleic-acid-containing oligomer to suppress wild-type
      PCR amplification and to enhance melting analysis with a mutation-specific
      detection probe.

PMID- 16000453
TI  - Countrywide spread of community- and hospital-acquired extended-spectrum beta
      lactamase (CTX-M-15)-producing Enterobacteriaceae in Lebanon.
AB  - A prospective study was carried out to assess the extent of carriage of extended
      spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae at both hospital and
      community levels in Lebanon. A total of 1,442 fecal samples were collected from
      hospital-based patients and 58 from health care workers of six Lebanese tertiary
      care general hospitals located in different areas of Lebanon between January and
      March 2003. A total of 382 fecal samples were also collected from healthy
      subjects between April and June 2003. The samples analysis led to the
      identification of 118 strains as ESBL producers based on the synergistic effects
      between clavulanate and selected beta-lactams (ceftazidime and cefotaxime). These
      strains were isolated from 72 subjects: 61 patients, 2 health care workers, and 9
      healthy subjects. One representative strain per subject was selected, and a total
      of 72 nonduplicate ESBL producers, including a high majority of Escherichia coli
      (n = 56), Klebsiella pneumoniae (n = 9), Enterobacter cloacae (n = 6), and
      Citrobacter freundii (n = 1), were characterized. The molecular analysis revealed
      that the majority of the strains (83%) express CTX-M-15 ESBL (pI 8.6). SHV-5a
      ESBL (pI 8.2) was produced by 18% of the strains. DNA macrorestriction analysis
      of ESBL-producing E. coli presented 38 different genotypes, revealing the absence
      of clonal link among these strains. In addition to the fact that the present
      study highlights the emergence and the countrywide dissemination of CTX-M-15
      producing E. coli in Lebanon, it represents the first report of an SHV-5a
      producing C. freundii.

PMID- 16000454
TI  - Uncultivated phylotypes and newly named species associated with primary and
      persistent endodontic infections.
AB  - Endodontic infections have been traditionally studied by culture methods, but
      recent reports showing that over 50% of the oral microbiota is still uncultivable
      (B. J. Paster et al., J. Bacteriol. 183:3770-3783, 2001) raise the possibility
      that many endodontic pathogens remain unknown. This study intended to investigate
      the prevalence of several uncultivated oral phylotypes, as well as newly named
      species in primary or persistent endodontic infections associated with chronic
      periradicular diseases. Samples were taken from the root canals of 21 untreated
      teeth and 22 root-filled teeth, all of them with radiographic evidence of
      periradicular bone destruction. Genomic DNA was isolated directly from each
      sample, and 16S rRNA gene-based nested or heminested PCR assays were used to
      determine the presence of 13 species or phylotypes of bacteria. Species-specific
      primers had already been validated in the literature or were developed by
      aligning closely related 16S rRNA gene sequences. Species specificity for each
      primer pair was confirmed by running PCRs against a panel of several oral
      bacteria and by sequencing DNA from representative positive samples. All species
      or phylotypes were detected in at least one case of primary infections. The most
      prevalent species or phylotypes found in primary infections were Dialister
      invisus (81%), Synergistes oral clone BA121 (33%), and Olsenella uli (33%). Of
      the target bacteria, only these three species were detected in persistent
      infections. Detection of uncultivated phylotypes and newly named species in
      infected root canals suggests that there are previously unrecognized bacteria
      that may play a role in the pathogenesis of periradicular diseases.

PMID- 16000455
TI  - Identification of two distinct hybridization groups in the genus Hafnia by 16S
      rRNA gene sequencing and phenotypic methods.
AB  - A collection of 52 strains belonging to the Hafnia alvei complex were subjected
      to molecular (16S rRNA gene sequencing) and biochemical analysis. Based upon 16S
      rRNA gene sequencing results, two genetic groups were identified which correspond
      with previously recognized DNA hybridization group 1 (ATCC 13337(T) and ATCC
      29926; n = 23) and DNA hybridization group 2 (ATCC 29927; n = 29). Of 46
      biochemical tests used to characterize hafniae, 19 reactions (41%) yielded
      variable results. Of these 19 tests, 6 were determined to have discriminatory
      value in the separation of DNA groups 1 and 2, with malonate utilization found to
      be the most differential test. Test results of malonate utilization alone
      correctly assigned 90% of Hafnia isolates to their correct DNA group.

PMID- 16000456
TI  - Multilocus DNA sequence comparisons rapidly identify pathogenic molds.
AB  - The increasing incidence of opportunistic fungal infections necessitates rapid
      and accurate identification of the associated fungi to facilitate optimal patient
      treatment. Traditional phenotype-based identification methods utilized in
      clinical laboratories rely on the production and recognition of reproductive
      structures, making identification difficult or impossible when these structures
      are not observed. We hypothesized that DNA sequence analysis of multiple loci is
      useful for rapidly identifying medically important molds. Our study included the
      analysis of the D1/D2 hypervariable region of the 28S ribosomal gene and the
      internal transcribed spacer (ITS) regions 1 and 2 of the rRNA operon. Two hundred
      one strains, including 143 clinical isolates and 58 reference and type strains,
      representing 43 recognized species and one possible new species, were examined.
      We generated a phenotypically validated database of 118 diagnostic alleles. DNA
      length polymorphisms detected among ITS1 and ITS2 PCR products can differentiate
      20 of 33 species of molds tested, and ITS DNA sequence analysis permits
      identification of all species tested. For 42 of 44 species tested, conspecific
      strains displayed >99% sequence identity at ITS1 and ITS2; sequevars were
      detected in two species. For all 44 species, identifications by genotypic and
      traditional phenotypic methods were 100% concordant. Because dendrograms based on
      ITS sequence analysis are similar in topology to 28S-based trees, we conclude
      that ITS sequences provide phylogenetically valid information and can be utilized
      to identify clinically important molds. Additionally, this phenotypically
      validated database of ITS sequences will be useful for identifying new species of
      pathogenic molds.

PMID- 16000457
TI  - Genetic divergence of Campylobacter fetus strains of mammal and reptile origins.
AB  - Campylobacter fetus is a gram-negative bacterial pathogen of both humans and
      animals. Two subspecies have been identified, Campylobacter fetus subsp. fetus
      and Campylobacter fetus subsp. venerealis, and there are two serotypes, A and B.
      To further investigate the genetic diversity among C. fetus strains of different
      origins, subspecies, and serotypes, we performed multiple genetic analyses by
      utilizing random amplification of polymorphic DNA (RAPD), pulsed-field gel
      electrophoresis (PFGE), and DNA-DNA hybridization. All 10 primers used for the
      RAPD analyses can distinguish C. fetus strains of reptile and mammal origin, five
      can differentiate between C. fetus subsp. fetus and C. fetus subsp. venerealis
      strains, and four showed differences between type A and type B isolates from
      mammals. PFGE with SmaI and SalI digestion showed varied genome patterns among
      different C. fetus strains, but for mammalian C. fetus isolates, genome size was
      well conserved (mean, 1.52 +/- 0.06 Mb for SmaI and 1.52 +/- 0.05 Mb for SalI).
      DNA-DNA hybridization demonstrated substantial genomic-homology differences
      between strains of mammal and reptile origin. In total, these data suggest that
      C. fetus subsp fetus strains of reptile and mammal origin have genetic divergence
      more extensive than that between the two subspecies and that between the type A
      and type B strains. Combining these studies with sequence data, we conclude that
      there has been substantial genetic divergence between Campylobacter fetus of
      reptile and mammal origin. Diagnostic tools have been developed to differentiate
      among C. fetus isolates for taxonomic and epidemiologic uses.

PMID- 16000458
TI  - Emergence of virulent methicillin-resistant Staphylococcus aureus strains
      carrying Panton-Valentine leucocidin genes in The Netherlands.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the Panton
      Valentine leucocidin (PVL) genes have been reported worldwide and are a serious
      threat to public health. The PVL genes encode a highly potent toxin which is
      involved in severe skin infections and necrotizing pneumonia, even in previously
      healthy individuals. We assessed the prevalence of PVL-positive MRSA in The
      Netherlands for two periods of time: (i) 1987 through 1995 and (ii) 2000 and
      2002, and determined their characteristics by using multilocus sequence typing
      and staphylococcal chromosome cassette (SCCmec) typing. It was found that up to
      15% of all MRSA isolates detected in The Netherlands harbored the PVL genes. Most
      PVL-positive MRSA isolates were obtained from severe soft tissue infections in
      relatively young individuals. The first PVL-positive MRSA described in The
      Netherlands, isolated in 1988, was a single-locus variant of the "Berlin"
      epidemic MRSA clone. The 20 PVL-positive MRSA isolates studied in 2000 and 2002
      consisted of five different sequence types (STs) that belonged to four clonal
      complexes. One of the STs, ST80, is considered to be a widespread European clone
      and was the most predominant ST (60%) in this study, while ST37 had never been
      found to be associated with PVL-positive MRSA. Most isolates harbored SCCmec type
      IV, a supposed marker for community-acquired MRSA. The number and type of
      virulence-associated genes varied among the different STs.

PMID- 16000459
TI  - Use of an automated multiple-locus, variable-number tandem repeat-based method
      for rapid and high-throughput genotyping of Staphylococcus aureus isolates.
AB  - Fast and reliable genotyping methods that allow real-time epidemiological
      surveillance would be instrumental to monitoring of the spread of methicillin
      resistant Staphylococcus aureus. We describe an automated variable-number tandem
      repeat-based method for the rapid genotyping of Staphylococcus aureus. Multiplex
      PCR amplifications with eight primer pairs that target gene regions with variable
      numbers of tandem repeats were resolved by microcapillary electrophoresis and
      automatically assessed by cluster analysis. This genotyping technique was
      evaluated for its discriminatory power and reproducibility with clinical isolates
      of various origins, including a panel of control strains previously characterized
      by several typing methods and collections from either long-term carriers or
      defined nosocomial outbreaks. All steps of this new procedure were developed to
      ensure a rapid turnaround time and moderate cost. The results obtained suggest
      that this rapid approach is a valuable tool for the genotyping of S. aureus
      isolates in real time.

PMID- 16000460
TI  - A Panton-Valentine leucocidin (PVL)-positive community-acquired methicillin
      resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a
      multiple-drug resistance plasmid, and other more-typical PVL-negative MRSA
      strains found in Japan.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was
      collected from children with bullous impetigo in 2003 and 2004. One strain
      collected in 2003 was Panton-Valentine leucocidin (PVL) positive. In 2004, a
      multiple-drug-resistant PVL(+) CA-MRSA strain was isolated from an athlete with a
      cutaneous abscess. These strains were analyzed by multilocus sequence typing, spa
      typing, agr typing, coagulase typing, staphylococcal cassette chromosome mec
      (SCCmec) typing, PCR assay for 30 virulence genes, drug susceptibility testing,
      pulsed-field gel electrophoresis, and for plasmids. The two Japanese PVL(+) CA
      MRSA strains belonged to the globally extant ("pandemic") sequence type 30 (ST30)
      with SCCmec IV. A transmissible, multiple-drug resistance plasmid emerged in such
      ST30 strains. The PVL(-) CA-MRSA strains ("domestic" CA-MRSA) accumulated for
      bullous impetigo, exhibiting new genotypes. Hospital-acquired MRSA of ST91 (but
      not pandemic ST5) shared common features with the PVL(-) CA-MRSA strain.

PMID- 16000461
TI  - Dissemination of methicillin-resistant staphylococci among healthy Japanese
      children.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA), regarded as a tenacious
      pathogen in the hospital, has recently become increasingly prevalent as a
      community pathogen. We evaluated the prevalence and characteristics of
      methicillin-resistant staphylococci in the Japanese community by testing nasal
      samples of 818 children of five day care centers and two kindergartens in three
      districts. We found that methicillin-resistant staphylococci are already
      prevalent among healthy children. Among 818 children, 35 children (4.3%) carried
      MRSA and 231 children (28.2%) carried methicillin-resistant coagulase-negative
      staphylococci (MRC-NS). The types of staphylococcal cassette chromosome mec
      (SCCmec) found among 44 MRSA isolates were as follows: type IIa, 11 isolates;
      type IIb, 19 isolates; and type IV, 14 isolates. The type IIb SCCmec element was
      a new SCCmec element found in this study. Eleven (25%) strains which belonged to
      clonal complex 5 (CC5) carried type IIa SCCmec, and they produced type 2
      coagulase and toxic shock syndrome toxin 1. They were indistinguishable from
      health care-associated MRSA (H-MRSA) strains in Japan, represented by strain
      N315. On the other hand, 33 (75%) strains, most of which belonged to CC78 or
      CC91, carried small SCCmec elements, such as type IIb or type IV, and they
      produced type 1 or type 3 coagulase and exfoliative toxin. The data indicated
      that MRSA clones distinct from H-MRSA have disseminated in healthy children. The
      fact that MRC-NS strains were prevalent in the community suggested that they
      might serve as a reservoir for the SCCmec element carried by MRSA strains
      disseminated in the community.

PMID- 16000462
TI  - Differential distribution and expression of Panton-Valentine leucocidin among
      community-acquired methicillin-resistant Staphylococcus aureus strains.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an
      emerging threat worldwide. CA-MRSA strains differ from hospital-acquired MRSA
      strains in their antibiotic susceptibilities and genetic backgrounds. Using
      several genotyping methods, we clearly define CA-MRSA at the genetic level and
      demonstrate that the prototypic CA-MRSA strain, MW2, has spread as a homogeneous
      clonal strain family that is distinct from other CA-MRSA strains. The Panton
      Valentine leucocidin (PVL)-encoding genes, lukF and lukS, are prevalent among CA
      MRSA strains and have previously been associated with CA-MRSA infections. To
      better elucidate the role of PVL in the pathogenesis of CA-MRSA, we first
      analyzed the distribution and expression of PVL among different CA-MRSA strains.
      Our data demonstrate that PVL genes are differentially distributed among CA-MRSA
      strains and, when they are present, are always transcribed, albeit with strain-to
      strain variability of transcript levels. To directly test whether PVL is critical
      for the pathogenesis of CA-MRSA, we evaluated the lysis of human
      polymorphonuclear leukocytes (PMNs) during phagocytic interaction with PVL
      positive and PVL-negative CA-MRSA strains. Unexpectedly, there was no correlation
      between PVL expression and PMN lysis, suggesting that additional virulence
      factors underlie leukotoxicity and, thus, the pathogenesis of CA-MRSA.

PMID- 16000463
TI  - Spatial organization and composition of the mucosal flora in patients with
      inflammatory bowel disease.
AB  - The composition and spatial organization of the mucosal flora in biopsy specimens
      from patients with inflammatory bowel disease (IBD; either Crohn's disease or
      ulcerative colitis), self-limiting colitis, irritable-bowel syndrome (IBS), and
      healthy controls were investigated by using a broad range of fluorescent
      bacterial group-specific rRNA-targeted oligonucleotide probes. Each group
      included 20 subjects. Ten patients who had IBD and who were being treated with
      antibiotics were also studied. Use of nonaqueous Carnoy fixative to preserve the
      mucus layer was crucial for detection of bacteria adherent to the mucosal surface
      (mucosal bacteria). No biofilm was detectable in formalin-fixed biopsy specimens.
      Mucosal bacteria were found at concentrations greater than 10(9)/ml in 90 to 95%
      of IBD patients, 95% of patients with self-limiting colitis, 65% of IBS patients,
      and 35% of healthy controls. The mean density of the mucosal biofilm was 2 powers
      higher in IBD patients than in patients with IBS or controls, and bacteria were
      mostly adherent. Bacteroides fragilis was responsible for >60% of the biofilm
      mass in patients with IBD but for only 30% of the biofilm mass in patients with
      self-limiting colitis and <15% of the biofilm mass in patients with IBS. In
      contrast, bacteria which positively hybridized with the probe specific for
      Eubacterium rectale-Clostridium coccoides accounted for >40% of the biofilm in
      IBS patients but for <15% of the biofilm in IBD patients. In patients treated
      with (5-ASA) or antibiotics, the biofilm could be detected with 4,6-diamidino-2
      phenylindole but did not hybridize with fluorescence in situ hybridization
      probes. A Bacteroides fragilis biofilm is the main feature of IBD. This was not
      previously recognized due to a lack of appropriate tissue fixation. Both 5-ASA
      and antibiotics suppress but do not eliminate the adherent biofilm.

PMID- 16000465
TI  - Molecular diversity of Bacillus anthracis in Italy.
AB  - We used multiple-locus variable-number tandem repeat analysis (MLVA) to type 64
      Bacillus anthracis isolates from outbreaks that have occurred during the past 40
      years in Italy. MLVA of the 64 isolates revealed 10 unique genotypes; 9 of these
      genotypes and the majority of isolates (63/64) belonged to the previously
      described genetic cluster A1.a. Within the A1.a isolates, two previously
      described genotypes (G1 and G3), which differ by a single mutation in the pX01
      locus, account for the majority of isolates in the country (53/63). The low
      diversity of B. anthracis genotypes in Italy suggests a single, dominant
      historical introduction, followed by limited localized differentiation.

PMID- 16000464
TI  - Rapid diagnosis of bacterial meningitis by real-time PCR and fluorescence in situ
      hybridization.
AB  - Real-time PCR and fluorescence in situ hybridization (FISH) were evaluated as
      rapid methods for the diagnosis of bacterial meningitis and compared to standard
      diagnostic procedures. For PCR, a LightCycler approach was chosen, implementing
      eubacterial and specific PCR assays for the most relevant bacteria. For FISH, a
      similar probe set containing eubacterial and specific probes was composed of
      published and newly designed probes. Both methods were evaluated by use of
      cerebrospinal fluid (CSF) samples from patients with suspected bacterial
      meningitis. For all microscopy- and culture-positive samples (n = 28), the
      eubacterial PCR was positive. In addition, all identifiable pathogens were
      detected with specific PCR assays, according to an algorithm based on the Gram
      stain. The FISH method detected the pathogen in 13 of 18 positive samples. While
      the FISH method remained negative for all microscopy- and culture-negative
      samples (n = 113), the eubacterial PCR was positive for five of these samples.
      Sequencing of the amplicon revealed the presence of Neisseria meningitidis,
      Streptococcus agalactiae, and Haemophilus influenzae in three of these five
      samples. In addition, samples with discordant results by culture and microscopy
      were successfully investigated by PCR (10 samples) and FISH (5 samples). In
      conclusion, PCR is a highly sensitive tool for rapid diagnosis of bacterial
      meningitis. FISH is less sensitive but is useful for the identification of CSF
      samples showing bacteria in the Gram stain. Based on our results, an approach for
      laboratory diagnosis of meningitis including PCR and FISH is discussed.

PMID- 16000466
TI  - Characterization of a new species of adenovirus in falcons.
AB  - In 1996, a disease outbreak occurred at a captive breeding facility in Idaho,
      causing anorexia, dehydration, and diarrhea or sudden death in 72 of 110 Northern
      aplomado falcons (Falco femoralis septentrionalis) from 9 to 35 days of age and
      in 6 of 102 peregrine falcons (Falco peregrinus) from 14 to 25 days of age. Sixty
      two Northern aplomado and six peregrine falcons died. Epidemiologic analyses
      indicated a point source epizootic, horizontal transmission, and increased
      relative risk associated with cross-species brooding of eggs. Primary lesions in
      affected birds were inclusion body hepatitis, splenomegaly, and enteritis. The
      etiology in all mortalities was determined by molecular analyses to be a new
      species of adenovirus distantly related to the group I avian viruses, serotypes 1
      and 4, Aviadenovirus. In situ hybridization and PCR demonstrated that the virus
      was epitheliotropic and lymphotropic and that infection was systemic in the
      majority of animals. Adeno-associated virus was also detected by PCR in most
      affected falcons, but no other infectious agents or predisposing factors were
      found in any birds. Subsequent to the 1996 epizootic, a similar disease caused by
      the same adenovirus was found over a 5-year period in orange-breasted falcons
      (Falco deiroleucus), teita falcons (Falco fasciinucha), a merlin (Falco
      columbarius), a Vanuatu peregrine falcon (Falco peregrinus nesiotes), and
      gyrfalcon x peregrine falcon hybrids (Falco rusticolus/peregrinus) that died in
      Wyoming, Oklahoma, Minnesota, and California. These findings indicate that this
      newly recognized adenovirus is widespread in western and midwestern North America
      and can be a primary pathogen in different falcon species.

PMID- 16000467
TI  - Isolation and epidemiology of falcon adenovirus.
AB  - An adenovirus was detected by electron microscopy in tissues from falcons that
      died during an outbreak of inclusion body hepatitis and enteritis that affected
      neonatal Northern aplomado (Falco femoralis septentrionalis) and peregrine (Falco
      peregrinus anatum) falcons. Molecular characterization has identified the falcon
      virus as a new member of the aviadenovirus group (M. Schrenzel, J. L. Oaks, D.
      Rotstein, G. Maalouf, E. Snook, C. Sandfort, and B. Rideout, J. Clin. Microbiol.
      43:3402-3413, 2005). In this study, the virus was successfully isolated and
      propagated in peregrine falcon embryo fibroblasts, in which it caused visible and
      reproducible cytopathology. Testing for serum neutralizing antibodies found that
      infection with this virus was limited almost exclusively to falcons. Serology
      also found that wild and captive peregrine falcons had high seropositivity rates
      of 80% and 100%, respectively, although clinical disease was rarely reported in
      this species. These data implicate peregrine falcons as the natural host and
      primary reservoir for the virus. Other species of North American falcons,
      including aplomado falcons, had lower seropositivity rates of 43 to 57%. Falcon
      species of tropical and/or island origin were uniformly seronegative, although
      deaths among adults of these species have been described, suggesting they are
      highly susceptible. Chickens and quail were uniformly seronegative and not
      susceptible to infection, indicating that fowl were not the source of infection.
      Based on the information from this study, the primary control of falcon
      adenovirus infections should be based on segregation of carrier and susceptible
      falcon species.

PMID- 16000468
TI  - Potential secondary pathogenic role for bovine herpesvirus 4.
AB  - Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus with no clear disease
      association. Previous studies have demonstrated that macrophages can harbor
      persistent BoHV-4. We found that the addition of prostaglandin E2 (PGE2) to
      bovine macrophage cells persistently infected with BoHV-4 increases viral
      replication. Because opportunistic infection can increase PGE2 production, we
      propose a link between opportunistic infection, PGE2 production, and BoHV-4
      replication.

PMID- 16000469
TI  - Development of a novel protein microarray method for serotyping Salmonella
      enterica strains.
AB  - An antibody microarray assay was developed for Salmonella serotyping based on the
      Kauffmann-White scheme. A model (8 by 15) array was constructed using 35
      antibodies for identification of 20 common Salmonella serovars and evaluated
      using 117 target and 73 nontarget Salmonella strains. The assay allowed complete
      serovar identification of 86 target strains and partial identification of 30
      target strains and allowed exclusion of the 73 nontarget strains from the target
      serovars.

PMID- 16000470
TI  - Clinical use of 16S rRNA gene sequencing to identify Mycoplasma felis and M.
      gateae associated with feline ulcerative keratitis.
AB  - Routine bacterial cultures of corneal scrapings from seven cats with either
      ulcerative feline keratitis, keratomalacia, or both yielded colonies which were
      identified by 16S rRNA gene sequencing as Mycoplasma felis (six cases) and
      Mycoplasma gateae (one case). Identification of the pathogens allowed the use of
      less empirical and more organism-specific therapy.

PMID- 16000471
TI  - Prevalence of SCCmec type IV in nosocomial bloodstream isolates of methicillin
      resistant Staphylococcus aureus.
AB  - Over a period of 7 months, 151 consecutive methicillin-resistant Staphylococcus
      aureus blood isolates were evaluated. None was community acquired. Twenty (13%)
      were susceptible to four or more antimicrobials, and 95% of these isolates were
      identified as SCCmec type IV. Molecular typing demonstrated four patterns, with
      one predominant pattern. Although usually community acquired, SCCmec type IV in
      our setting is clearly nosocomial.

PMID- 16000472
TI  - Sensitivity and specificity of a rapid rRNA gene probe assay for simultaneous
      identification of Staphylococcus aureus and detection of mecA.
AB  - rRNA gene sequences were used for identification and target adequacy controls in
      a DNA probe assay to identify isolates as Staphylococcus and, more specifically,
      as S. aureus within 1 hour. mecA status was simultaneously determined using a
      specific DNA probe. The target adequacy control guarded against false-negative
      mecA results.

PMID- 16000473
TI  - Rapid detection of human metapneumovirus strains in nasopharyngeal aspirates and
      shell vial cultures by monoclonal antibodies.
AB  - Monoclonal antibodies to human metapneumovirus (hMPV) were developed for direct
      fluorescent antibody (DFA) staining of nasopharyngeal aspirates from 40 infants
      with respiratory infections, as well as for hMPV identification in shell vial
      cultures. With reference to reverse transcription-PCR, DFA staining showed
      sensitivity, specificity, and positive and negative predictive values of 73.9%,
      94.1%, 94.4%, and 72.7%, respectively. Monoclonal antibodies are useful for
      direct hMPV detection.

PMID- 16000474
TI  - Human clinical isolates of Corynebacterium diphtheriae and Corynebacterium
      ulcerans collected in Canada from 1999 to 2003 but not fitting reporting criteria
      for cases of diphtheria.
AB  - A 5-year collection of Corynebacterium diphtheriae and Corynebacterium ulcerans
      human clinical isolates yielded nine isolates from blood cultures of patients
      with invasive infections, stressing the importance of C. diphtheriae as a serious
      blood-borne pathogen. Seven percent of C. diphtheriae and 100% of C. ulcerans
      isolates produced diphtheria toxin, demonstrating that toxigenic corynebacteria
      continue to circulate.

PMID- 16000475
TI  - Comparison of conventional susceptibility testing, penicillin-binding protein 2a
      latex agglutination testing, and mecA real-time PCR for detection of oxacillin
      resistance in Staphylococcus aureus and coagulase-negative Staphylococcus.
AB  - Penicillin-binding protein (PBP) 2a latex agglutination was compared with
      conventional susceptibility testing and mecA real-time PCR for the detection of
      oxacillin resistance in Staphylococcus aureus. Inoculum volume and induction with
      oxacillin were PBP 2a testing variables. For coagulase-negative Staphylococcus,
      an increased inoculum volume of 10 microl greatly reduced the number of isolates
      requiring induction.

PMID- 16000476
TI  - Repeated occurrence of diverse extended-spectrum beta-lactamases in minor
      serotypes of food-borne Salmonella enterica subsp. enterica.
AB  - Screening of Greek nontyphoid salmonellae from 2000 to 2002 yielded three
      extended-spectrum beta-lactamase (ESBL)-producing human isolates. Salmonella
      enterica serotype Brandenburg harbored a multiresistant SHV-5 gene-carrying
      plasmid. S. enterica serotype Blockley and S. enterica serotype Hadar harbored a
      TEM-52 gene-carrying plasmid. An S. enterica serotype Virchow strain producing
      plasmid-mediated CTX-M-32 was isolated twice from poultry end products. All ESBL
      plasmids were self-transferable and carried by clones currently common in Greece.

PMID- 16000477
TI  - Evaluation of real-time reverse transcriptase PCR and real-time loop-mediated
      amplification assays for severe acute respiratory syndrome coronavirus detection.
AB  - We compared the performance of a recently established real-time loop-mediated
      amplification (LAMP) assay with the one from a highly sensitive quantitative PCR
      assay. None of these assays produced false-positive results in this study. For
      samples isolated from patients within the first 3 days of disease onset, the
      detection rate of the quantitative PCR assay was higher (14 of 15 were positive)
      than the LAMP assay (9 of 15 were positive). By contrast, the detection rates of
      these assays toward specimens sampled from patients with more than 3 days of
      illness were similar (32 of 44 for PCR and 33 of 44 for LAMP were positive). The
      simpler operation of LAMP might be a possible solution for on-site diagnosis.

PMID- 16000478
TI  - Improved sensitivity of sputum smear microscopy after processing specimens with
      C18-carboxypropylbetaine to detect acid-fast bacilli: a study of United States
      bound immigrants from Vietnam.
AB  - The goal of this study was to evaluate the effect of the specimen-processing
      method that uses the detergent C18-carboxypropylbetaine (CB-18) on the
      sensitivity of acid-fast bacillus (AFB) staining. Vietnamese immigrants with
      abnormal chest radiographs provided up to three sputum specimens, which were
      examined for acid-fast bacilli by use of direct auramine and Ziehl-Neelsen
      staining. The remaining sputum was split; half was cultured, and the other half
      was incubated with CB-18 for 24 h, centrifuged, and examined for AFB by both
      staining methods. CB-18 processing improved the sensitivity of AFB staining by 20
      to 30% (only differences in auramine sensitivity were statistically significant)
      but reduced specificity by approximately 20% (P < 0.05). These findings have
      direct utility for overseas migrant tuberculosis screening programs, for which
      maximizing test sensitivity is a major objective.

PMID- 16000480
TI  - Age-related prevalence and distribution of nontuberculous mycobacterial species
      among patients with cystic fibrosis.
AB  - We studied the prevalence and species distribution of nontuberculous mycobacteria
      (NTM) in relation to age in 385 patients with cystic fibrosis (CF) (mean age +/-
      standard deviation [range], 12.0 +/- 6.1 [1 to 24] years; sex ratio, 0.53)
      attending three Parisian centers. The overall prevalence of NTM in sputum was
      8.1% (31 out of 385). The following NTM were isolated (n = 33): Mycobacterium
      abscessus (n = 13, 39.4%), Mycobacterium avium complex (MAC) (n = 7, 21.2%),
      Mycobacterium gordonae (n = 6, 18.2%), and other (n = 7, 21.2%). Sixteen patients
      met the American Thoracic Society microbiological criteria for NTM infection,
      including 11 patients positive for M. abscessus, 4 for MAC, and 1 for MAC and
      Mycobacterium kansasii. The overall prevalence of NTM was significantly lower in
      patients under 15 years old than for patients equal to or more than 15 years old
      (4.8 versus 14.9%, respectively; P = 0.001). M. abscessus was isolated at all
      ages, while MAC was not recovered before 15 years (prevalence of 0.0 and 5.2% in
      patients aged 1 to 14 and 15 to 24, respectively; P = 0.001).

PMID- 16000479
TI  - Use of PCR analyses to define the distribution of Ralstonia species recovered
      from patients with cystic fibrosis.
AB  - Two new PCR assays (for Ralstonia species and Ralstonia respiraculi), together
      with previously published PCR assays, were used to assess Ralstonia isolates
      recovered from 111 cystic fibrosis patients. Ralstonia mannitolilytica accounted
      for 46% of isolates, while R. respiraculi and Ralstonia pickettii accounted for
      19% and 18%, respectively. Ralstonia basilensis and Ralstonia metallidurans,
      species not previously recovered from human samples, were also identified.

PMID- 16000481
TI  - Possible tick-borne human enterovirus resulting in aseptic meningitis.
AB  - Enterovirus-specific genetic sequences were isolated from two Amblyomma
      americanum tick pools. Identical genetic sequences were later obtained from
      cerebrospinal fluid of a patient with aseptic meningitis and a recent history of
      tick attachment. These observations suggest the possibility of an emerging tick
      borne human enterovirus associated with aseptic meningitis.

PMID- 16000482
TI  - Interpretive criteria for use of AccuProbe for identification of Mycobacterium
      avium complex directly from 7H9 broth cultures.
AB  - Rapid identification of Mycobacterium avium complex (MAC) is possible by use of
      AccuProbe (Gen-Probe, San Diego, Calif.). To evaluate the reliability of the MAC
      AccuProbe for testing 7H9 cultures inoculated with broth from MGIT cultures
      positive for acid-fast bacilli or growth on a solid medium, we compared probe
      results to results obtained by sequencing a portion of the 16S rRNA gene.
      Isolates were sequenced if the MAC probe result was <100,000 relative light units
      (RLU) or if it was > or =100,000 RLU and the colony morphology was not classic or
      there were two colony types. For the 1,389 cultures tested in phase 1, conducted
      to evaluate cutoff values for the MAC probe in testing of 7H9 cultures inoculated
      with broth from MGIT cultures, the sensitivity and specificity of the MAC
      AccuProbe were 97.7% and 88.8%, respectively, according to the manufacturer's
      interpretive criteria (> or =30,000 RLU is positive). If the cutoff for a
      positive result were 80,000 RLU, the specificity would be 100% and the
      sensitivity 92.3%. Of the 344 isolates in phase 2, which was conducted to confirm
      the 80,000-RLU cutoff for a positive result and therefore included only isolates
      with a MAC probe result of < or =100,000 RLU, 13 of 16 with results of > or
      =30,000 but <80,000 RLU were identified as mycobacteria other than MAC, including
      five Mycobacterium tuberculosis complex isolates. These data support the use of
      80,000 RLU as the cutoff for a positive result in testing of 7H9 broth cultures
      with the MAC AccuProbe.

PMID- 16000483
TI  - Bacteriology of acute and chronic ethmoid sinusitis.
AB  - Aspirates from 26 acutely and 17 chronically infected ethmoid sinuses were
      studied. Thirty-seven aerobes and 10 anaerobes were recovered from isolates from
      patients with acute sinusitis. Streptococcus pneumoniae and Haemophilus
      influenzae were predominant. Twenty-seven aerobes and 41 anaerobes were found in
      isolates from patients with chronic sinusitis. The predominant isolates were
      anaerobic gram-negative bacilli and Peptostreptococcus spp.

PMID- 16000484
TI  - Use of a single serum sample for diagnosis of acute toxoplasmosis in pregnant
      women and other adults.
AB  - Using a single serum sample for testing for immunoglobulin G (IgG) Toxoplasma
      antibodies, differences in sensitivity of the dye test (which measures primarily
      IgG antibodies) and an IgG enzyme immunoassay were found useful for very early
      diagnosis of acute Toxoplasma gondii infection.

PMID- 16000485
TI  - Frequent detection of Epstein-Barr Virus and cytomegalovirus but not JC virus DNA
      in cerebrospinal fluid samples from human immunodeficiency virus-infected
      patients in northern Thailand.
AB  - Applying nested-PCRs, we frequently detected DNA of Epstein-Barr virus and
      cytomegalovirus but not JC virus in cerebrospinal fluid samples from 140 human
      immunodeficiency virus-infected patients with central nervous system symptoms in
      northern Thailand. Despite the low incidence of primary central nervous system
      lymphoma or cytomegalovirus encephalitis among Thai AIDS patients, Epstein-Barr
      virus and cytomegalovirus infections in the central nervous system are common.

PMID- 16000486
TI  - Multiplex PCR for identification of seven Streptococcus pneumoniae serotypes
      targeted by a 7-valent conjugate vaccine.
AB  - Here we describe a Streptococcus pneumoniae one-step multiplex PCR assay which
      identifies by amplicon size the seven capsular polysaccharide serotypes targeted
      by the 7-valent conjugate vaccine. The multiplex PCR assay was used to blindly
      assay clinical isolates recovered during 1999 in the Republic of Ireland from
      cases of invasive disease whose serotypes were previously determined by classical
      methods.

PMID- 16000487
TI  - Molecular evidence that nasal carriage of Staphylococcus aureus plays a role in
      respiratory tract infections of critically ill patients.
AB  - The relationship between nasal Staphylococcus aureus carriage and lower
      respiratory tract infections was studied in 16 critically ill patients. S. aureus
      strains from nasal and bronchial samples were characterized by pulsed-field gel
      electrophoresis. In all but one case, nasal and bronchial strains were
      genetically identical in the same patients.

PMID- 16000488
TI  - Evaluation of seaFAST, a rapid fluorescent in situ hybridization test, for
      detection of Helicobacter pylori and resistance to clarithromycin in paraffin
      embedded biopsy sections.
AB  - A commercially available rapid fluorescent in situ hybridization (FISH) test,
      (seaFAST H. pylori Combi-Kit; SeaPro Theranostics International, Lelystad, The
      Netherlands) was used to simultaneously detect the presence of Helicobacter
      pylori and determine clarithromycin susceptibility in paraffin-embedded biopsy
      sections. The FISH method was found to be 97% sensitive, 94% specific for the
      detection of H. pylori and comparable to agar dilution for the detection of
      resistance to clarithromycin.

PMID- 16000489
TI  - Disk diffusion testing using Candida sp. colonies taken directly from CHROMagar
      Candida medium may decrease time required to obtain results.
AB  - We compared results of disk diffusion antifungal susceptibility testing from
      Candida sp. strains passaged on CHROMagar and on potato dextrose agar. The
      overall categorical agreements for fluconazole and voriconazole disk testing were
      95% and 98% with 0% and 0.5% very major errors, respectively. Disk diffusion
      testing by the CLSI (formerly NCCLS) M44-A method can be performed accurately by
      taking inocula directly from CHROMagar.

PMID- 16000490
TI  - Intra- and interpatient variability of the hsp65 and 16S-23S intergenic gene
      region in Mycobacterium abscessus strains from patients with cystic fibrosis.
AB  - To establish the exact pathogenic role of Mycobacterium abscessus in cystic
      fibrosis (CF), molecular tests are required for accurate identification. Forty
      eight M. abscessus isolates from seven patients with CF were analyzed by sequence
      analysis for sequence variants within the hsp65 gene and the 16S-23S intergenic
      sequence (ITS). We detected two different hsp65 genes and correspondingly two ITS
      sequevars belonging to M. abscessus type I and type II.

PMID- 16000491
TI  - Evaluation of the COBAS TaqMan 48 real-time PCR system for quantitation of
      hepatitis B virus DNA.
AB  - The purpose of this study is to evaluate the usefulness of the new real-time PCR
      COBAS TaqMan 48 analyzer, comparing it to the existing COBAS AMPLICOR HBV MONITOR
      based on conventional PCR technology. The study used 104 samples from different
      patients. No differences were found in the sensitivity of the tests. There was an
      excellent correlation between the sample with a viral load within the dynamic
      range of the two tests (r = 0.938). The COBAS TaqMan test has a wider linear
      range, and this fact enables quantifying of the viral load without diluting the
      sample.

PMID- 16000492
TI  - Identification of unique bacterial gene segments from Streptococcus mutans with
      potential relevance to dental caries by subtraction DNA hybridization.
AB  - Using DNA subtractive hybridization, 49 unique gene segments were identified from
      a strain of Streptococcus mutans that was isolated from a patient with severe
      early childhood caries (S-ECC). Further hybridization with DNA from other S.
      mutans strains isolated from both caries-active and caries-free subjects yielded
      five unique sequences of DNA common to strains associated with S-ECC.

PMID- 16000493
TI  - First infection with VanD-type glycopeptide-resistant Enterococcus faecium in
      Europe.
AB  - We report the first strain of glycopeptide-resistant Enterococcus faecium from
      Europe that contains a vanD allele isolated from blood cultures of an
      immunocompromised patient hospitalized in a French university hospital. Based on
      phenotypic results, PCR sequencing, pulsed-field gel electrophoresis, and
      Southern blotting, the isolate was assigned to E. faecium with a chromosomally
      located VanD allele most closely related to the VanD1 allele.

PMID- 16000494
TI  - Detection of Tropheryma whipplei DNA in clinical specimens by LightCycler real
      time PCR.
AB  - A real-time PCR method using the LightCycler (Roche Applied Science,
      Indianapolis, IN) was compared to a conventional PCR assay for the detection of
      Tropheryma whipplei in 321 clinical specimens. The LightCycler method had
      sensitivity and specificity comparable to the conventional method but required
      considerably less labor and time (3 h versus 3 to 5 days).

PMID- 16000495
TI  - Nosocomial outbreak of pediatric gastroenteritis caused by CTX-M-14-type extended
      spectrum beta-lactamase-producing strains of Salmonella enterica serovar London.
AB  - CTX-M-14-type extended-spectrum beta-lactamase was first detected in Salmonella
      enterica serovar London strains which were isolated from three hospitalized
      pediatric patients with gastroenteritis. The isolates had pulsed-field gel
      electrophoresis patterns identical to those of the previously isolated
      antimicrobial-susceptible strains from community-acquired gastroenteritis,
      suggesting the susceptible clone acquired the resistance.

PMID- 16000496
TI  - Isolation of an atypical strain of Actinobacillus pleuropneumoniae serotype 1
      with a truncated lipopolysaccharide outer core and no O-antigen.
AB  - A field isolate of Actinobacillus pleuropneumoniae, the causative agent of
      porcine fibrinohemorrhagic necrotizing pleuropneumonia, was sent to the
      diagnostic laboratory for serotyping. The isolate presented a clear reaction,
      with both polyclonal antibodies against serotype 1 and monoclonal antibodies
      against the capsular polysaccharide of serotype 1. It also exhibited a PCR
      profile of Apx toxins expected for serotype 1. The isolate, however, failed to
      react with monoclonal antibodies against the O-antigen of serotype 1
      lipopolysaccharide (LPS), suggesting a rough phenotype. The lipid A-core region
      of the isolate migrated faster than the corresponding region of the serotype 1
      reference strain S4074 by Tricine-sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, suggesting the presence of a truncated core. Sugar analysis and
      mass spectrometry analysis of the O-deacylated LPS from the field isolate were
      consistent with the absence of O-antigen and truncation of the outer core
      compared to the wild-type reference strain. Experimental infection of pigs
      confirmed the virulence of the isolate. This is the first report of an isolate of
      A. pleuropneumoniae serotype 1 with a truncated outer core and a rough LPS
      phenotype. Veterinary diagnostic laboratories should be vigilant, since
      infections caused by such an isolate will not be detected by serological tests
      based on LPS O-antigen.

PMID- 16000497
TI  - Description of Kingella potus sp. nov., an organism isolated from a wound caused
      by an animal bite.
AB  - We report the isolation and characterization of a hitherto unknown gram-negative,
      rod-shaped Neisseria-like organism from an infected wound resulting from a bite
      from a kinkajou. Based on both phenotypic and phylogenetic evidence, it is
      proposed that the unknown organism be classified as a new species, Kingella potus
      sp. nov.

PMID- 16000498
TI  - Does resistance to pyrazinamide accurately indicate the presence of Mycobacterium
      bovis?
AB  - Mycobacterium bovis is best identified by screening those isolates of the
      Mycobacterium tuberculosis complex that have any pyrazinamide (PZA) resistance,
      using a confirmatory test such as spoligotyping, biochemical testing, or genomic
      deletion analysis. The sensitivity for detection of M. bovis is lowered to 82%
      when only PZA-monoresistant isolates are screened.

PMID- 16000499
TI  - Identification of Vibrio parahaemolyticus pandemic group-specific DNA sequence by
      genomic subtraction.
AB  - A genomic subtraction between a pandemic Vibrio parahaemolyticus and a
      nonpandemic strain that seemed to be clonally related was performed. A
      subtractive DNA fragment was identified to be a part of a 16-kbp insertion
      sequence which was present in almost all pandemic strains but not in nonpandemic
      strains tested.

PMID- 16000500
TI  - Bacteremia caused by Janibacter melonis.
AB  - We report a case of bacteremia caused by Janibacter melonis, a recently described
      aerobic actinomycete originally isolated from a spoiled oriental melon. Our
      patient's blood culture isolate was identified by partial 16S rRNA gene
      sequencing. This is the first report of the recovery of Janibacter species from
      humans.

PMID- 16000501
TI  - High fatality rate of Epstein-Barr virus-associated lymphoproliferative disorder
      occurring after bone marrow transplantation with rabbit antithymocyte globulin
      conditioning regimens.
AB  - Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (EBV-LPD)
      following bone marrow transplantation can be fatal. The major risk factors for
      the development of EBV-LPD are ex vivo T-cell depletion or in vivo T-cell
      depletion with either antithymocyte globulin (ATG) or monoclonal anti-T-cell
      antibodies. Between March 1999 and January 2001, a total of 23 transplants with
      ATG of equine source (20 transplants) and ATG of rabbit source (3 transplants)
      used as part of the preparatory regimen were performed at the Barbara Ann
      Karmanos Cancer Institute in Detroit, Mich. The three patients who received
      rabbit ATG developed EBV-LPD between 60 and 90 days following bone marrow
      transplantation. However, there were no cases of EBV-LPD in the equine group.
      Treatment given in these cases consisted of tapering immunosuppression, antiviral
      therapy, unprocessed donor lymphocyte infusion, mobilized peripheral blood
      progenitor cell rescue infusion (one patient), and chemotherapy (one patient).
      All three patients died of complications from EBV-LPD. The association of rabbit
      ATG with the development of EBV-LPD suggests that patients receiving rabbit ATG
      as part of their preparatory regimens require close monitoring of the EBV viral
      load and possible early intervention with antiviral therapy.

PMID- 16000502
TI  - Toxoplasmosis after renal transplantation: implications of a missed diagnosis.
AB  - We describe a renal transplant patient with a primary Toxoplasma gondii infection
      presenting as pneumonitis, with subsequent chorioretinitis and encephalitis. The
      diagnostic challenges of T. gondii infection in immunocompromised patients are
      discussed.

PMID- 16000503
TI  - First case of human cryptococcosis due to Cryptococcus neoformans var. gattii in
      Spain.
AB  - We report the first case of human cryptococcosis due to Cryptococcus neoformans
      var. gattii described in our country, which was presented as brain cryptococcoma
      in an immunocompetent patient. An extensive sampling of the patient's environment
      was carried out to find the source of infection.

PMID- 16000504
TI  - Fatal reactivation of postnatal cytomegalovirus infection with rapid emergence of
      ganciclovir resistance in an infant after allogeneic stem cell transplantation.
AB  - Human cytomegalovirus (HCMV) can cause serious problems after hematopoietic stem
      cell transplantation. The death of a pediatric transplant recipient after
      reactivation of a postnatal HCMV infection with bilateral retinitis and
      pneumonitis is described. Sequencing of the HCMV UL97 region revealed a
      compartment-specific mutation (H520Q) in urine conferring ganciclovir resistance.

PMID- 16000505
TI  - Transmission of Mycobacterium tuberculosis from human to cattle.
AB  - We describe the first transmission of Mycobacterium tuberculosis from human to
      cattle confirmed by molecular typing of isolates involved in the transmission.
      IS6110-based restriction fragment length polymorphism analysis showed that the
      isolates from the cattle and farm worker who suffered from pulmonary tuberculosis
      1 year prior to this case were the same strains.

PMID- 16000506
TI  - Simultaneous detection of "Rickettsia mongolotimonae" in a patient and in a tick
      in Greece.
AB  - Rickettsia conorii, a spotted fever group rickettsia which is transmitted by
      Rhipicephalus sp. complex ticks, was considered until now the only pathogenic
      rickettsia prevalent in Greece. Here, we report the presence of "Rickettsia
      mongolotimonae" (proposed name) detected simultaneously in a patient and in a
      Hyalomma anatolicum excavatum tick, sampled on the patient.

PMID- 16000507
TI  - Discordant rise in galactomannan antigenemia in a patient with resolving
      Aspergillosis, renal failure, and ongoing hemodialysis.
AB  - We describe the case of a patient with improving invasive aspergillosis and
      paradoxically rising serum galactomannan levels in the presence of chronic renal
      failure and ongoing hemodialysis. Dialysate tested negative for galactomannan,
      demonstrating the inability of treatments such as hemodialysis to clear
      Aspergillus antigen from serum. In patients with renal failure and aspergillosis,
      rising serum galactomannan levels may not necessarily signify progressive
      infection.

PMID- 16000508
TI  - Bacteremia caused by an undescribed species of Janibacter.
AB  - A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated
      from the blood of a patient with acute myeloid leukemia. It was identified by 16S
      rRNA gene sequencing as a previously undescribed species of Janibacter. The
      isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and
      glycopeptides.

PMID- 16000509
TI  - Isolation of Actinobaculum schaalii and Actinobaculum urinale from a patient with
      chronic renal failure.
AB  - We report on the isolation of two species of Actinobaculum from blood culture of
      a patient with chronic renal failure. The two isolates were distinct with regard
      to their morphological and biochemical characteristics. Subsequent 16S rRNA gene
      sequencing classified the two species as Actinobaculum schaalii and A. urinale.

PMID- 16000510
TI  - Involvement of streptococcal mitogenic exotoxin Z in streptococcal toxic shock
      syndrome.
AB  - We report a nonfatal case of streptococcal toxic shock syndrome (STSS) caused by
      a Streptococcus pyogenes emm118 strain encoding a novel variant of streptococcal
      mitogenic exotoxin Z (SMEZ-34). This variant was responsible for the major
      mitogenic activity in the cell culture supernatant. Patient sera showed
      seroconversion toward SMEZ, implying a role for this toxin in STSS.

PMID- 16000511
TI  - Inhibition of growth of Streptococcus mutans, methicillin-resistant
      Staphylococcus aureus, and vancomycin-resistant enterococci by kurarinone, a
      bioactive flavonoid isolated from Sophora flavescens.

PMID- 16000512
TI  - Primer sequence modification enhances hepatitis C virus genotype coverage.

PMID- 16000513
TI  - Meningitis due to vancomycin-resistant Enterococcus faecium successfully treated
      with combined intravenous and intraventricular chloramphenicol.

PMID- 16000514
TI  - Detection of acid-fast bacilli in postlysis debris of clinical specimens improves
      the reliability of PCR.

PMID- 16000515
TI  - Enterotoxigenic Escherichia coli isolated from surface water in urban and rural
      areas of Bangladesh.

PMID- 16000516
TI  - Molecular mycological diagnosis and correct antimycotic treatments.

PMID- 16000517
TI  - Unraveling interlimb interactions underlying bimanual coordination.
AB  - Three sources of interlimb interactions have been postulated to underlie the
      stability characteristics of bimanual coordination but have never been evaluated
      in conjunction: integrated timing of feedforward control signals, phase
      entrainment by contralateral afference, and timing corrections based on the
      perceived error of relative phase. In this study, the relative contributions of
      these interactions were discerned through systematic comparisons of five tasks
      involving rhythmic flexion-extension movements about the wrist, performed
      bimanually (in-phase and antiphase coordination) or unimanually with or without
      comparable passive movements of the contralateral hand. The main findings were
      the following. 1) Contralateral passive movements during unimanual active
      movements induced phase entrainment to interlimb phasing of either 0 degrees (in
      phase) or 180 degrees (antiphase). 2) Entrainment strength increased with the
      passive movements' amplitude, but was similar for in-phase and antiphase
      movements. 3) Coordination of unimanual active movements with passive movements
      of the contralateral hand (kinesthetic tracking) was characterized by similar
      bilateral EMG activity as observed in active bimanual coordination. 4) During
      kinesthetic tracking the timing of the movements of the active hand was modulated
      by afference-based error corrections, which were more pronounced during in-phase
      coordination. 5) Indications of in-phase coordination being more stable than
      antiphase coordination were most prominent during active bimanual coordination
      and marginal during kinesthetic tracking. Together the results indicated that
      phase entrainment by contralateral afference contributed equally to the stability
      of in-phase and antiphase coordination, and that differential stability of these
      patterns depended predominantly on integrated timing of feedforward signals, with
      only a minor role for afference-based error corrections.

PMID- 16000518
TI  - Corticofugal feedback for collicular plasticity evoked by electric stimulation of
      the inferior colliculus.
AB  - Focal electric stimulation of the auditory cortex, 30-min repetitive acoustic
      stimulation, and auditory fear conditioning each evoke shifts of the frequency
      tuning curves [hereafter, best frequency (BF) shifts] of cortical and collicular
      neurons. The short-term collicular BF shift is produced by the corticofugal
      system and primarily depends on the relationship in BF between a recorded
      collicular and a stimulated cortical neuron or between the BF of a recorded
      collicular neuron and the frequency of an acoustic stimulus. However, it has been
      unknown whether focal electric stimulation of the inferior colliculus evokes the
      collicular BF shift and whether the collicular BF shift, if evoked, depends on
      corticofugal feedback. In our present research with the awake big brown bat, we
      found that focal electric stimulation of collicular neurons evoked the BF shifts
      of collicular neurons located near the stimulated ones; that there were two types
      of BF shifts: centripetal and centrifugal BF shifts, i.e., shifts toward and
      shifts away from the BF of stimulated neurons, respectively; and that the
      development of these collicular BF shifts was blocked by inactivation of the
      auditory cortex. Our data indicate that the collicular BF shifts (plasticity)
      evoked by collicular electric stimulation depended on corticofugal feedback. It
      should be noted that collicular BF shifts also depend on acetylcholine because it
      has been demonstrated that atropine (an antagonist of muscarinic acetylcholine
      receptors) applied to the IC blocks the development of collicular BF shifts.

PMID- 16000519
TI  - Increases in corticospinal tract function by treadmill training after incomplete
      spinal cord injury.
AB  - In this study, we examined if several months of intensive locomotor training
      increases the function of spared corticospinal tract pathways after chronic
      spinal cord injury (SCI) in association with the recovery of locomotor function.
      Transcranial magnetic stimulation (TMS) at incrementing levels of intensity was
      applied over the motor cortex supplying either the tibialis anterior or vastus
      lateralis muscles, and the resulting peak-to-peak amplitude of the motor-evoked
      potentials (MEPs) were measured to obtain a recruitment curve both before and
      after training. In the majority of subjects (7/8), 3-5 mo of daily intensive
      training increased the responses to TMS in at least one of the leg muscles tested
      (9/13). On average, across all muscles tested MEP(max), which was evoked at high
      stimulation intensities, increased by 46% and MEP(h), which was evoked at
      intermediate stimulation intensities, increased by 45% (both significantly
      different from 0), indicating an increase in corticospinal tract connectivity
      from training. The slope of the sigmoid function fit to the recruitment curve
      increased by 24% after training (significantly different), indicating an
      expansion and/or increased excitability of corticospinal circuits supplying
      muscles to the lower leg. We also observed that the average duration of the
      silent period measured at MEP(max) increased after training from 130 to 178 ms,
      suggesting that training had effects on cortical circuits thought to mediate this
      long-lasting inhibition. The percentage increase in MEP(max) was positively and
      significantly correlated to the degree of locomotor recovery as assessed by the
      WISCI II score, the distance a subject could walk in 6 min, and the amplitude of
      the locomotor EMG activity, suggesting that the corticospinal tract, in part,
      mediated the functional locomotor recovery produced from training.

PMID- 16000520
TI  - Modulation of membrane potential in mesothoracic moto- and interneurons during
      stick insect front-leg walking.
AB  - During walking, maintenance and coordination of activity in leg motoneurons
      requires intersegmental signal transfer. In a semi-intact preparation of the
      stick insect, we studied membrane potential modulations in mesothoracic (middle
      leg) motoneurons and local premotor nonspiking interneurons that were induced by
      stepping of a front leg on a treadmill. The activity in motoneurons ipsi- and
      contralateral to the stepping front leg was recorded from neuropilar processes.
      Motoneurons usually exhibited a tonic depolarization of < or =5 mV throughout
      stepping sequences. This tonic depolarization depended on membrane potential and
      was found to reverse in the range of -32 to -47 mV. It was accompanied by a mean
      membrane resistance decrease of approximately 12%. During front-leg stepping, an
      increased spike activity to depolarizing current pulses was observed in 73% of
      contralateral flexor motoneurons that were tested. Motoneurons ipsilateral to the
      walking front leg exhibited phasic membrane potential modulations coupled to
      steps in accordance with previously published results. Coupling patterns were
      typical for a given motoneuron pool. Local nonspiking mesothoracic interneurons
      that provide synaptic drive to tibial motoneurons also contribute to the
      modulation of membrane potential of tibial motoneurons during front-leg walking.
      We hypothesize that the tonic depolarization of motoneurons during walking is a
      cellular correlate of arousal that usually increases effectiveness of phasic
      excitation in supporting motoneuron firing.

PMID- 16000521
TI  - Disruption of left-right reciprocal coupling in the spinal cord of larval lamprey
      abolishes brain-initiated locomotor activity.
AB  - In this study, contributions of left-right reciprocal coupling mediated by
      commissural interneurons in spinal locomotor networks to rhythmogenesis were
      examined in larval lamprey that had longitudinal midline lesions in the rostral
      spinal cord [8 --> 30% body length (BL), relative distance from the head] or
      caudal spinal cord (30 --> 50% BL). Motor activity was initiated from brain
      locomotor command systems in whole animals or in vitro brain/spinal cord
      preparations. After midline lesions in the caudal spinal cord in whole animals
      and in vitro preparations, left-right alternating burst activity could be
      initiated in rostral and usually caudal regions of spinal motor networks. In in
      vitro preparations, blocking synaptic transmission in the rostral cord abolished
      burst activity in caudal hemi-spinal cords. After midline lesions in the rostral
      spinal cord in whole animals, left-right alternating muscle burst activity was
      present in the caudal and sometimes the rostral body. After spinal cord
      transections at 30% BL, rhythmic burst activity usually was no longer generated
      by rostral hemi-spinal cords. For in vitro preparations, very slow burst activity
      was sometimes present in isolated right and left rostral hemi-spinal cords, but
      the rhythmicity for this activity appeared to originate from the brain, and the
      parameters of the activity were significantly different from those for normal
      locomotor activity. In summary, in larval lamprey under these experimental
      conditions, left and right hemi-spinal cords did not generate rhythmic locomotor
      activity in response to descending inputs from the brain, suggesting that left
      right reciprocal coupling contributes to both phase control and rhythmogenesis.

PMID- 16000522
TI  - Affects of aging on receptive fields in rat primary auditory cortex layer V
      neurons.
AB  - Advanced age is commonly associated with progressive cochlear pathology and
      central auditory deficits, collectively known as presbycusis. The present study
      examined central correlates of presbycusis by measuring response properties of
      primary auditory cortex (AI) layer V neurons in the Fischer Brown Norway rat
      model. Layer V neurons represent the major output of AI to other cortical and
      subcortical regions (primarily the inferior colliculus). In vivo single-unit
      extracellular recordings were obtained from 114 neurons in aged animals (29-33
      mo) and compared with 105 layer V neurons in young-adult rats (4-6 mo). Three
      consecutive repetitions of a pure-tone receptive field map were run for each
      neuron. Age was associated with fewer neurons exhibiting classic V/U-shaped
      receptive fields and a greater percentage of neurons with more Complex receptive
      fields. Receptive fields from neurons in aged rats were also less reliable on
      successive repetitions of the same stimulus set. Aging was also associated with
      less firing during the stimulus in V/U-shaped receptive field neurons and more
      firing during the stimulus in Complex neurons, which were generally associated
      with inhibited firing in young controls. Finally, neurons in aged rats with
      Complex receptive fields were more easily driven by current pulses delivered to
      the soma. Collectively, these findings provide support for the notion that age is
      associated with diminished signal-to-noise coding by AI layer V neurons and are
      consistent with other research suggesting that GABAergic neurotransmission in AI
      may be compromised by aging.

PMID- 16000523
TI  - Functional organization of visual cortex in the prosimian bush baby revealed by
      optical imaging of intrinsic signals.
AB  - Cells in primary visual cortex (V1) of primates and carnivores respond most
      strongly to a visual stimulus presented to one eye, in a particular visual field
      location, and at a particular orientation. Each of these stimulus attributes is
      mapped across the cortical surface, and, in macaque monkeys and cats, strong
      geometrical relationships exist between these feature maps. In macaque V1 and V2,
      correlations between feature maps and cytochrome oxidase (CO)-rich modules have
      also been observed. To see if such relationships reflect a conserved principle of
      V1 functional architecture among primate species, we examined these maps in the
      prosimian bush baby, a species that has been proposed to represent the ancestral
      primate organization. We found that the layout of individual feature maps in bush
      baby V1 is similar to that of other primates, but we found an entirely different
      organization of orientation preference in bush baby V2 compared with that
      reported in simian primates. Another striking distinction between bush baby and
      simian species is that we observed no strong relationships among maps of
      orientation, ocular dominance, and CO blobs in V1. Thus our findings suggest that
      precise relationships between feature maps are not a common element of the
      functional organization in all primates and that such relationships are not
      necessary for achieving basic coverage of stimulus feature combinations. In
      addition, our results suggest that specific relationships between feature maps in
      V1, and the subdivision of V2 into functional compartments, may have arisen
      comparatively late in the evolution of primates.

PMID- 16000524
TI  - Development of a robust central auditory synapse in congenital deafness.
AB  - Within the medial nucleus of the trapezoid body (MNTB) in the auditory brain
      stem, there is a large central synapse known as the calyx of Held, which mediates
      high-fidelity glutamatergic transmission. We investigated the effects of
      congenital deafness on the development of pre- and postsynaptic parameters of
      synaptic strength at the calyx of Held. Whole cell recordings of evoked
      excitatory postsynaptic currents (EPSCs) and immunohistochemistry of GluR1-4
      subunits were performed using brain stem slices from congenitally deaf or hearing
      mice at postnatal days P5 and P12. In both hearing and deaf mice there was a
      similar developmental decrease in the NMDA component of the evoked EPSC. There
      was a concurrent increase in release probability and number of release sites,
      contributing to a fivefold increase in evoked AMPA-mediated EPSC amplitude. The
      increase in release probability is opposite to that found in previous studies at
      the calyx of Held in the rat. There was also a seven- to eightfold increase in
      the size of the readily releasable pool of vesicles and a decrease in tetanic
      depression. The postsynaptic glutamate receptor subunits were similarly
      developmentally regulated and unaffected by deafness. GluR1 and 4 dominated at
      both ages. There was a decrease in expression of GluR1-3 from P5 to P12 and a
      shift from GluR2 to GluR3, indicating that AMPA receptor complexes at P12 are
      predominantly calcium-permeable. These results demonstrate that early development
      at this robust synapse proceeds normally with congenital deafness, suggesting
      that auditory nerve activity does not affect the development of synaptic strength
      at the calyx of Held.

PMID- 16000525
TI  - Disparity-tuning characteristics of neuronal responses to dynamic random-dot
      stereograms in macaque visual area V4.
AB  - Stereo processing begins in the striate cortex and involves several extrastriate
      visual areas. We quantitatively analyzed the disparity-tuning characteristics of
      neurons in area V4 of awake, fixating monkeys. Approximately half of the analyzed
      V4 cells were tuned for horizontal binocular disparities embedded in dynamic
      random-dot stereograms (RDSs). Their response preferences were strongly biased
      for crossed disparities. To characterize the disparity-tuning profile, we fitted
      a Gabor function to the disparity-tuning data. The distribution of V4 cells
      showed a single dense cluster in a joint parameter space of the center and the
      phase parameters of the fitted Gabor function; most V4 neurons were maximally
      sensitive to fine stereoscopic depth increments near zero disparity. Comparing
      single-cell responses with background multiunit responses at the same sites
      showed that disparity-sensitive cells were clustered within V4 and that nearby
      cells possessed similar preferred disparities. Consistent with a recent report by
      Hegde and Van Essen, the disparity tuning for an RDS drastically differed from
      that for a solid-figure stereogram (SFS). Disparity-tuning curves were generally
      broader for SFSs than for RDSs, and there was no correlation between the fitted
      Gabor functions' amplitudes, widths, or peaks for the two types of stereograms.
      The differences were partially attributable to shifts in the monocular images of
      an SFS. Our results suggest that the representation of stereoscopic depth in V4
      is suited for detecting fine structural features protruding from a background.
      The representation is not generic and differs when the stimulus is broad-band
      noise or a solid figure.

PMID- 16000526
TI  - Topographical characteristics of motor units of the lower facial musculature
      revealed by means of high-density surface EMG.
AB  - The objective of this study was to systematically characterize motor units (MUs)
      of the musculature of the lower face. MU endplate positions and principal muscle
      fiber orientations relative to facial landmarks were identified. This was done by
      the analysis of motor unit action potentials (MUAPs) in the surface
      electromyogram. Thirteen specially trained, healthy subjects performed selective
      contractions of the depressor anguli oris, depressor labii inferioris, mentalis,
      and orbicularis oris inferior muscles. Signals were recorded using recently
      developed, 0.3-mm thin and flexible high-density surface electromyography (sEMG)
      grids (120 channels). For each subject and each muscle and for different low
      contraction levels, representative MUAPs ("MU fingerprints") were extracted from
      the raw sEMG data according to their spatiotemporal amplitude characteristics. We
      then topographically characterized the lower facial MUs' endplate zones and main
      muscle fiber orientations on the individual faces of the subjects. These
      topographical MU parameters were spatially warped to correct for the different
      sizes and shapes of the faces of individual subjects. This electrophysiological
      study revealed a distribution of the lower facial MU endplates in more or less
      restricted, distinct clusters on the muscle often with eccentric locations. The
      results add substantially to the basic neurophysiologic and anatomical knowledge
      of the complex facial muscle system. They can also be used to establish objective
      guidelines for placement of conventional (surface or needle) EMG electrodes as
      well as for clinical investigations on neuromuscular diseases affecting the
      facial musculature. The localized endplate positions may also indicate optimal
      locations for botulinum toxin injection in the face.

PMID- 16000527
TI  - Anticonvulsant action of GABA in the high potassium-low magnesium model of
      ictogenesis in the neonatal rat hippocampus in vivo and in vitro.
AB  - Previous developmental studies in vitro suggested that the inhibitory
      neurotransmitter GABA exerts depolarizing and excitatory actions on the immature
      neurons and that depolarizing GABA is causally linked to ictal activity during
      the first weeks of postnatal life. However, remarkably little is known on the
      role of GABA in the generation of neonatal seizures in vivo. Here, using
      extracellular recordings from CA3 hippocampus, we studied the effects of GABA(A)
      acting drugs on electrographic seizures induced by local intrahippocampal
      injection of the epileptogenic agents (high K(+)/low Mg(2+)) in the
      nonanesthetized rats in vivo and in the hippocampal slices in vitro during the
      second postnatal week (postnatal days P8-12). We found that in vivo, the
      induction of ictal-like events was facilitated by co-infusion of high-K(+)/low
      Mg(2+) together with the GABA(A) antagonist bicuculline or gabazine. Moreover,
      the infusion of bicuculline alone caused ictal-like activity in approximately 30%
      of cases. Co-infusion of the GABA(A) receptor agonist isoguvacine or the GABA(A)
      positive allosteric modulator diazepam completely prevented high-K(+)/low Mg(2+)
      induced seizures. In in vitro studies using hippocampal slices, we also found
      that high-K(+)/low Mg(2+) produced ictal activity that was exacerbated by
      bicuculline and gabazine and reduced by isoguvacine. Thus in the model of high
      K(+)/low Mg(2+)-induced seizures both in in vivo and in vitro conditions, GABA,
      acting via GABA(A) receptors, has an anticonvulsant effect during the critical
      developmental period of enhanced excitability.

PMID- 16000528
TI  - Laminar organization of response properties in primary visual cortex of the gray
      squirrel (Sciurus carolinensis).
AB  - The gray squirrel (Sciurus carolinensis) is a diurnal highly visual rodent with a
      cone-rich retina. To determine which features of visual cortex are common to
      highly visual mammals and which are restricted to non-rodent species, we studied
      the laminar organization of response properties in primary visual area V1 of
      isoflurane-anesthetized squirrels using extra-cellular single-unit recording and
      sinusoidal grating stimuli. Of the responsive cells, 75% were tuned for
      orientation. Only 10% were directionally selective, almost all in layer 6, a
      layer receiving direct input from the dorsal lateral geniculate nucleus (LGN).
      Cone opponency was widespread but almost absent from layer 6. Median optimal
      spatial frequency tuning was 0.21 cycles/ degrees . Median optimal temporal
      frequency a high 5.3 Hz. Layer 4 had the highest percentage of simple cells and
      shortest latency (26 ms). Layers 2/3 had the lowest spontaneous activity and
      highest temporal frequency tuning. Layer 5 had the broadest spatial frequency
      tuning and most spontaneous activity. At the layer 4/5 border were sustained
      cells with high cone opponency. Simple cells, determined by modulation to
      drifting sinusoidal gratings, responded with shorter latencies, were more
      selective for orientation and direction, and were tuned to lower spatial
      frequencies. A comparison with other mammals shows that although the laminar
      organization of orientation selectivity is variable, the cortical input layers
      contain more linear cells in most mammals. Nocturnal mammals appear to have more
      orientation-selective neurons in V1 than diurnal mammals of similar size.

PMID- 16000529
TI  - Two populations of layer v pyramidal cells of the mouse neocortex: development
      and sensitivity to anesthetics.
AB  - Previous studies have shown that layer V pyramidal neurons projecting either to
      subcortical structures or the contralateral cortex undergo different
      morphological and electrophysiological patterns of development during the first
      three postnatal weeks. To isolate the determinants of this differential
      maturation, we analyzed the gene expression and intrinsic membrane properties of
      layer V pyramidal neurons projecting either to the superior colliculus (SC cells)
      or the contralateral cortex (CC cells) by combining whole cell recordings and
      single-cell RT-PCR in acute slices prepared from postnatal day (P) 5-7 or P21-30
      old mice. Among the 24 genes tested, the calcium channel subunits alpha1B and
      alpha1C, the protease Nexin 1, and the calcium-binding protein calbindin were
      differentially expressed in adult SC and CC cells and the potassium channel
      subunit Kv4.3 was expressed preferentially in CC cells at both stages of
      development. Intrinsic membrane properties, including input resistance, amplitude
      of the hyperpolarization-activated current, and action potential threshold,
      differed quantitatively between the two populations as early as from the first
      postnatal week and persisted throughout adulthood. However, the two cell types
      had similar regular action potential firing behaviors at all developmental
      stages. Surprisingly, when we increased the duration of anesthesia with ketamine
      xylazine or pentobarbital before decapitation, a proportion of mature SC cells,
      but not CC cells, fired bursts of action potentials. Together these results
      indicate that the two populations of layer V pyramidal neurons already start to
      differ during the first postnatal week and exhibit different firing capabilities
      after anesthesia.

PMID- 16000530
TI  - Investigation of the phenylalkylamine binding site in hKv1.3 (H399T), a mutant
      with a reduced C-type inactivated state.
AB  - To screen for residues of hKv1.3 important for current block by the
      phenylalkylamine verapamil, the inactivated-state-reduced H399T mutant was used
      as a background for mutagenesis studies. This approach was applied mainly to
      abolish the accumulation in the inactivated blocked state, recovery from which in
      the wild type is normally slow. Substitution of amino acids in the S6
      transmembrane helix indicated a heavy disruption of verapamil block by the A413C
      mutation, reducing the IC(50) from 2.4 to 267 microM. Subsequent scanning for
      verapamil moieties essential for current block was performed by application of
      derivatives with altered side groups. Neither the removal of the nitrile or the
      methyl group nor the addition of a methoxy group resulted in major variations of
      IC(50) values for hKv1.3 (H399T) current block. However, disruption of current
      block by A413C was 4- to 10-fold less pronounced for derivatives lacking the 4
      methoxy group of the (3,4-dimethoxyphenyl)ethylmethyl-amino part (devapamil) or
      all four methoxy groups (emopamil), respectively. Emopamil displayed a Hill
      coefficient of 2 for hKv1.3 (H399T/A413C) instead of 1 for hKv1.3 (H399T) current
      block. These results might indicate that the alteration of Ala413 modulates the
      access of phenylalkylamines to their binding site depending on the occupancy of
      the phenyl rings with methoxy groups. A computer-based docking model shows a
      subset of docked PAA conformations, with a spatial proximity between the (4
      methoxyphenyl)ethyl-methyl-amino group and Ala413. The PAA binding site might
      therefore include a binding pocket for the aromatic ring of the ethyl-methyl
      amino part in an S6-S6 interface gap.

PMID- 16000531
TI  - Hot bugs: body temperature of insects in sunshine.

PMID- 16000532
TI  - Running performance has a structural basis.
AB  - The body sizes of highly adapted human and other mammalian runners vary in
      accordance with specific performance needs. Sprint specialists are relatively
      massive and muscular while endurance specialists are conspicuously limited both
      in body and in muscle mass. We hypothesized that the greater body masses of
      faster specialists are directly related to the greater ground support forces
      required to attain faster running speeds. Using human runners as a test case, we
      obtained mean values for body mass, stature and racing speed for the world's
      fastest 45 male and female specialists, respectively, over the past 14 years
      (1990-2003) at each of eight standard track racing distances from 100 to 10,000
      m. Mass-specific ground support force requirements were estimated from racing
      speeds using generalized support force-speed relationships derived from 18
      athletic subjects. We find a single relationship between mass, stature and event
      specific ground support force requirements that spans the entire continuum of
      specializations and applies both to male and to female runners [body mass (kg) =
      mass-specific support force x stature2 (m) x a constant; N = 16 group means, R2 =
      0.97; where the ideal mass constant, D = 10 kg m(-2)]. We conclude that running
      performance has a common structural basis.

PMID- 16000533
TI  - The effect of spinning forces on spider silk properties.
AB  - A new forced silking procedure has been developed that allows measurement of the
      low forces involved in the silking process and, subsequently, retrieval and
      tensile testing of the samples spun at the measured silking forces. A strong
      correlation between silking force and tensile behaviour of spider silk has been
      established. Fibres spun at high silking force--compared with the conventional
      yield stress--are stiff and show stress-strain curves previously found in
      forcibly silked fibres. By contrast, fibres spun at low and very low silking
      forces are more compliant, and their tensile behaviour corresponds to that of
      fibres naturally spun by the spider or to fibres subjected to maximum
      supercontraction, respectively. It has also been found that samples retrieved
      from processes with significant variations in the silking force are largely
      variable in terms of force-displacement curves, although reproducibility improves
      if force is re-scaled into stress. Fibres retrieved from processes with constant
      silking force show similar tensile properties both in terms of force-displacement
      and stress-strain curves.

PMID- 16000534
TI  - Does intracellular metabolite diffusion limit post-contractile recovery in burst
      locomotor muscle?
AB  - Post-metamorphic growth in the blue crab entails an increase in body mass that
      spans several orders of magnitude. The muscles that power burst swimming in these
      animals grow hypertrophically, such that small crabs have fiber diameters that
      are typical of most cells (<60 microm) while in adult animals the fibers are
      giant (>600 microm). Thus, as the animals grow, their muscle fibers cross and
      greatly exceed the surface area to volume ratio (SA:V) and intracellular
      diffusion distance threshold that is adhered to by most cells. Large fiber size
      should not impact burst contractile function, but post-contractile recovery may
      be limited by low SA:V and excessive intracellular diffusion distances. A number
      of changes occur in muscle structure, metabolic organization and metabolic flux
      during development to compensate for the effects of increasing fiber size. In the
      present study, we examined the impact of intracellular metabolite diffusive flux
      on the rate of post-contractile arginine phosphate (AP) resynthesis in burst
      locomotor muscle from small and large animals. AP recovery was measured following
      burst exercise, and these data were compared to a mathematical reaction-diffusion
      model of aerobic metabolism. The measured rates of AP resynthesis were
      independent of fiber size, while simulations of aerobic AP resynthesis yielded
      lower rates in large fibers. These contradictory findings are consistent with
      previous observations that there is an increased reliance on anaerobic metabolism
      for post-contractile metabolic recovery in large fibers. However, the model
      results suggest that the interaction between mitochondrial ATP production rates,
      ATP consumption rates and diffusion distances yield a system that is not
      particularly close to being limited by intracellular metabolite diffusion. We
      conclude that fiber SA:V and O2 flux exert more control than intracellular
      metabolite diffusive flux over the developmental changes in metabolic
      organization and metabolic fluxes that characterize these muscles.

PMID- 16000535
TI  - Sucking while swimming: evaluating the effects of ram speed on suction generation
      in bluegill sunfish Lepomis macrochirus using digital particle image velocimetry.
AB  - It is well established that suction feeding fish use a variable amount of
      swimming (ram) during prey capture. However, the fluid mechanical effects of ram
      on suction feeding are not well established. In this study we quantified the
      effects of ram on the maximum fluid speed of the water entering the mouth during
      feeding as well as the spatial patterns of flow entering the mouth of suction
      feeding bluegill sunfish Lepomis macrochirus. Using Digital Particle Image
      Velocimetry (DPIV) and high-speed video, we observed the flow in front of the
      mouth of three fish using a vertical laser sheet positioned on the mid-sagittal
      plane of the fish. From this we quantified the maximum fluid speed (measured at a
      distance in front of the mouth equal to one half of the maximum mouth diameter),
      the degree of focusing of water flow entering the mouth, and the shape of the
      ingested volume of water. Ram speed in 41 feeding sequences, measured at the time
      of maximum gape, ranged between 0 and 25 cm s(-1), and the ratio of ram speed to
      fluid speed ranged from 0.1% to 19.1%. In a regression ram speed did not
      significantly affect peak fluid speed, but with an increase in ram speed the
      degree of focusing of water entering the mouth increased significantly, and the
      shape of the ingested volume of water became more elongate and narrow. The
      implications of these findings are that (1) suction feeders that employ ram of
      between 0% and 20% of fluid speed sacrifice little in terms of the fluid speeds
      they generate and (2) ram speed enhances the total body closing speed of the
      predator.

PMID- 16000536
TI  - Spatial and temporal patterns of water flow generated by suction-feeding bluegill
      sunfish Lepomis macrochirus resolved by Particle Image Velocimetry.
AB  - The suction-feeding fish generates a flow field external to its head in order to
      draw prey into the mouth. To date there are very few empirical measurements that
      characterize the fluid mechanics of suction feeding, particularly the temporal
      and spatial patterns of water velocity in front of the fish. To characterize the
      flow in front of suction-feeding bluegill sunfish Lepomis macrochirus,
      measurements with high spatial (<1 mm) and temporal (500 Hz) resolution were
      taken using Particle Image Velocimetry (PIV). In an analysis separate from the
      PIV, high-speed video sequences were used for a novel method of visually tracking
      every seed particle for the duration of each feeding in order to determine
      directly the total parcel of water that the fish ingests. PIV measurements and
      particle tracking show that water is drawn from all around the mouth. Fluid
      velocity decreases rapidly with distance from the mouth and is only significant
      (>5% of speed at the mouth) within roughly 1 mouth diameter of the fish. Suction
      feeders gain little in terms of extending this flow field by even substantial
      increases in the fluid speed at the mouth opening. Instead, the chief advantage
      of increased flow speed at the mouth may be the increased magnitude of generated
      forces within the space very close to the mouth. After scaling of the velocity
      field based on size of the mouth opening and the measured fluid speed at a fixed
      position, the measured velocity profiles for all feedings are very similar to one
      another, so that a functional relationship for the magnitude of fluid speed as a
      function of distance from the predator mouth is presented and shown to be
      accurate over the range of kinematic variables tested. This relationship
      describes the velocity field both along the centerline of the fish and along
      transects lying at an angle to the centerline within both the mid-sagittal and
      frontal planes. Comparison of the time-resolved fluid velocity measurements to
      gape kinematics demonstrate that peak fluid speed occurs simultaneously with 95%
      of peak gape, showing that the bluegill maximizes nearly simultaneously both the
      generated forces and size of the region over which these forces act. The
      magnitude of peak fluid speed during each strike decreases as a function of
      increasing time to peak gape (r2 = 0.87), demonstrating a strong relationship
      between the rate of buccal cavity expansion and maximum generated flow speed.

PMID- 16000537
TI  - Aquaporin-3 expressed in the basolateral membrane of gill chloride cells in
      Mozambique tilapia Oreochromis mossambicus adapted to freshwater and seawater.
AB  - We have cloned a homologue of mammalian aquaporin-3 (AQP3) from gills of
      Mozambique tilapia using a reverse transcription-polymerase chain reaction (RT
      PCR). The deduced amino acid sequence shared 64-75% homology with other
      vertebrate AQP3 homologues. RT-PCR revealed that tilapia AQP3 was expressed in
      the brain, pituitary, kidney, spleen, intestine, skin, eye and gill in tilapia
      adapted to freshwater (FW) and seawater (SW). We also examined functional
      characteristics of tilapia AQP3 using Xenopus oocytes as an in vitro transcribed
      cRNA expression system. Osmotic water permeability (Pf) of Xenopus oocytes
      expressing tilapia AQP3 was about 30-fold higher than that of control oocytes,
      and was 80% inhibited by treatment with 0.3 mmol l(-1) HgCl2. Light-microscopic
      immunocytochemistry of branchial epithelia revealed that tilapia AQP3 was
      expressed in gill chloride cells of FW- and SW-adapted tilapia. Electron
      microscopic immunocytochemistry further demonstrated that tilapia AQP3 was
      localized in the basolateral membrane of gill chloride cells. Basolateral
      localization of AQP3 in gill chloride cells suggests that AQP3 is involved in
      regulatory volume changes and osmoreception, which could trigger functional
      differentiation of chloride cells.

PMID- 16000538
TI  - The effects of acclimation to reversed seasonal temperatures on the swimming
      performance of adult brown trout Salmo trutta.
AB  - Adult brown trout (Salmo trutta) were acclimatised to and maintained at seasonal
      temperatures (5 degrees C in winter; 15 degrees C in summer) and acclimated to
      reversed seasonal temperatures (15 degrees C in winter; 5 degrees C in summer)
      while exposed to the natural (i.e. seasonally variable) photoperiod. The mean
      critical swimming speeds (U(crit)) of animals acclimatised to the seasonal
      temperatures were similar, but more than 30% greater than those for fish
      acclimated to the reversed seasonal temperatures. The lower values of U(crit)
      that accompanied acclimation to reversed seasonal temperatures appeared largely
      to result from the inability of white muscle to function maximally, since the
      concentrations of lactate and ammonia in white muscle of fish swum to U(crit) at
      reversed seasonal temperatures were significantly lower than those in fish swum
      at seasonal temperatures. These observations, together with biochemical and
      morphometric attributes of muscle tissue, suggest that swimming ability is
      influenced, at least in part, by seasonal factors other than temperature. These
      data have important implications for the design of experiments using fish that
      experience predictable, usually seasonal, changes in their natural environment
      (temperature, dissolved oxygen, changes in water levels, etc.).

PMID- 16000540
TI  - The effects of cortisol administration on social status and brain monoaminergic
      activity in rainbow trout Oncorhynchus mykiss.
AB  - The hypothesis that circulating cortisol levels influence the outcome of social
      interactions in rainbow trout was tested. Juvenile rainbow trout Oncorhynchus
      mykiss were given a single intraperitoneal (i.p.) implant containing either
      cortisol (110 mg kg(-1) fish), or cortisol plus the glucocorticoid receptor
      antagonist RU486 (mifepristone; 1100 mg kg(-1) fish), and sampled after 5 days of
      social interactions with either a similar sized (<1.5% difference in fork length)
      or smaller conspecific (>5% difference). Within size-matched pairs of fish,
      cortisol treatment significantly increased the probability that the treated fish
      within each pair became subordinate, an effect that was abolished by simultaneous
      administration of RU486. Cortisol treatment also reduced the usual success of the
      larger fish within a pair to preferentially become dominant from 86% to 40% of
      pairs. To investigate one potential mechanism underlying the apparent effect of
      cortisol in predisposing trout to low social status, fish were treated with
      cortisol or cortisol+RU486 for 5 days, after which brain monoamines [5
      hydroxytryptamine (5-HT); dopamine (DA)] and their major metabolites [5
      hydroxyindolacetic acid (5-HIAA); 3,4-dihydroxy-phenylacetic acid (DOPAC)] were
      measured. Significant increases of serotonergic activity ([5-HIAA]/[5-HT] ratio)
      were detected in the telencephalon with cortisol treatment, an effect that was
      eliminated by simultaneous administration of RU486. Also, cortisol treatment
      significantly decreased dopaminergic activity in the telencephalon. Somewhat
      surprisingly, the effects of cortisol treatment on monoaminergic activity in the
      hypothalamus were opposite to those in the telencephalon. Moreover, in no case
      did administration of RU486 abolish these effects. These results suggest that the
      effects of cortisol on social status in rainbow trout may be mediated via the
      modulation of central signaling systems and subsequent changes in behaviour
      and/or competitive ability, although the exact site of action in the brain
      remains uncertain.

PMID- 16000539
TI  - Alkaline tide and nitrogen conservation after feeding in an elasmobranch (Squalus
      acanthias).
AB  - We investigated the consequences of feeding for acid-base balance, nitrogen
      excretion, blood metabolites and osmoregulation in the Pacific spiny dogfish.
      Sharks that had been starved for 7 days were surgically fitted with indwelling
      stomach tubes for gastric feeding and blood catheters for repetitive blood
      sampling and were confined in chambers, allowing measurement of ammonia-N and
      urea-N fluxes. The experimental meal infused via the stomach tube consisted of
      flatfish muscle (2% of body mass) suspended in saline (4% of body mass total
      volume). Control animals received only saline (4% of body mass). Feeding resulted
      in a marked rise in both arterial and venous pH and HCO3- concentrations at 3-9 h
      after the meal, with attenuation by 17 h. Venous P(O2) also fell. As there were
      negligible changes in P(CO2), the response was interpreted as an alkaline tide
      without respiratory compensation, associated with elevated gastric acid
      secretion. Urea-N excretion, which comprised >90% of the total, was unaffected,
      while ammonia-N excretion was very slightly elevated, amounting to <3% of the
      total-N in the meal over 45 h. Plasma ammonia-N rose slightly. Plasma urea-N,
      TMAO-N and glucose concentrations remained unchanged, while free amino acid and
      beta-hydroxybutyrate levels exhibited modest declines. Plasma osmolality was
      persistently elevated after the meal relative to controls, partially explained by
      a significant rise in plasma Cl-. This marked post-prandial conservation of
      nitrogen is interpreted as reflecting the needs for urea synthesis for
      osmoregulation and protein growth in animals that are severely N-limited due to
      their sporadic and opportunistic feeding lifestyle in nature.

PMID- 16000541
TI  - Gene expression after freshwater transfer in gills and opercular epithelia of
      killifish: insight into divergent mechanisms of ion transport.
AB  - We have explored the molecular basis for differences in physiological function
      between the gills and opercular epithelium of the euryhaline killifish Fundulus
      heteroclitus. These tissues are functionally similar in seawater, but in
      freshwater the gills actively absorb Na+ but not Cl-, whereas the opercular
      epithelium actively absorbs Cl- but not Na+. These differences in freshwater
      physiology are likely due to differences in absolute levels of gene expression
      (measured using real-time PCR), as several proteins important for Na+ transport,
      namely Na+,H+-exchanger 2 (NHE2), carbonic anhydrase 2 (CA2), Na+,HCO3-
      cotransporter 1, and V-type H+-ATPase, were expressed at 3- to over 30-fold
      higher absolute levels in the gills. In gills, transfer from 10% seawater to
      freshwater increased the activity of Na+,K+-ATPase by twofold (from 12 h to 7
      days), increased the expression of NHE2 (at 12 h) and CA2 (from 12 h to 7 days),
      and decreased the expression of NHE3 (from 12 h to 3 days). In opercular
      epithelium, NHE2 was not expressed; furthermore, Na+,K+-ATPase activity was
      unchanged after transfer to freshwater, CA2 mRNA levels decreased, and NHE3
      levels increased. Consistent with their functional similarities in seawater,
      killifish gills and opercular epithelium expressed Na+,K+-ATPase alpha 1a,
      Na+,K+,2Cl- cotransporter 1 (NKCC1), cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl- channel and the signalling protein 14-3-3a at similar
      absolute levels. Furthermore, NKCC1 and CFTR were suppressed equally in each
      tissue after freshwater transfer, and 14-3-3a mRNA increased in both. These
      results provide insight into the mechanisms of ion transport by killifish gills
      and opercular epithelia, and demonstrate a potential molecular basis for the
      differences in physiological function between these two organs.

PMID- 16000542
TI  - Renal regulation of plasma glucose in the freshwater rainbow trout.
AB  - This study examined the effects of prolonged hyperglycemia on renal handling of
      glucose and explored the in vivo pharmacological effects of phlorizin on glucose
      transport in the rainbow trout. The transport of glucose was examined by
      experimentally elevating the rate of renal glucose reabsorption via infusion of
      the fish with exogenous glucose at a rate of 70 micromol kg(-1) h(-1) and by
      inactivating the glucose transporters via the simultaneous administration of
      phlorizin (1 micromol kg(-1) h(-1)). Glucose was reabsorbed against a
      concentration gradient, until plasma glucose levels reached approximately 22
      micromol l(-1) and the transport maximum of glucose in the kidney (approximately
      145 micromol kg(-1) h(-1)) was exceeded. At this point, glucose was lost to the
      urine, resulting in glucosuria. Glucosuria affected water reabsorption,
      approximately doubling the water clearance ratio, and resulted in osmotic
      diuresis. This in turn reduced Na+ reabsorption, increasing the amount lost to
      the urine from 0.5% to 2% of the filtered load. Glucose reabsorption was found to
      be correlated with Na+ reabsorption, though the latter was almost 10-fold higher
      than glucose transport rates. Phlorizin treatment reduced glucose reabsorption,
      although it did not block it entirely until 48-72 h of infusion. The glucosuria
      resulting from the blockade of the glucose transporters resulted in a similar
      osmotic diuresis and a greater Na+ loss to the urine (9% of filtered load). The
      results are discussed with respect to the net renal ;wasting' of glucose and the
      detrimental osmoregulatory and ionoregulatory effects associated with glucosuria
      caused by carbohydrate-rich diets.

PMID- 16000543
TI  - The mechanics of jumping versus steady hopping in yellow-footed rock wallabies.
AB  - The goal of our study was to explore the mechanical power requirements associated
      with jumping in yellow-footed rock wallabies and to determine how these
      requirements are achieved relative to steady-speed hopping mechanics. Whole body
      power output and limb mechanics were measured in yellow-footed rock wallabies
      during steady-speed hopping and moving jumps up to a landing ledge 1.0 m high
      (approximately 3 times the animals' hip height). High-speed video recordings and
      ground reaction force measurements from a runway-mounted force platform were used
      to calculate whole body power output and to construct a limb stiffness model to
      determine whole limb mechanics. The combined mass of the hind limb extensor
      muscles was used to estimate muscle mass-specific power output. Previous work
      suggested that a musculoskeletal design that favors elastic energy recovery, like
      that found in tammar wallabies and kangaroos, may impose constraints on
      mechanical power generation. Yet rock wallabies regularly make large jumps while
      maneuvering through their environment. As jumping often requires high power, we
      hypothesized that yellow-footed rock wallabies would be able to generate
      substantial amounts of mechanical power. This was confirmed, as we found net
      extensor muscle power outputs averaged 155 W kg(-1) during steady hopping and 495
      W kg(-1) during jumping. The highest net power measured reached nearly 640 W kg(
      1). As these values exceed the maximum power-producing capability of vertebrate
      skeletal muscle, we suggest that back, trunk and tail musculature likely play a
      substantial role in contributing power during jumping. Inclusion of this
      musculature yields a maximum power output estimate of 452 W kg(-1) muscle.
      Similar to human high-jumpers, rock wallabies use a moderate approach speed and
      relatively shallow leg angle of attack (45-55 degrees) during jumps.
      Additionally, initial leg stiffness increases nearly twofold from steady hopping
      to jumping, facilitating the transfer of horizontal kinetic energy into vertical
      kinetic energy. Time of contact is maintained during jumping by a substantial
      extension of the leg, which keeps the foot in contact with the ground.

PMID- 16000544
TI  - Dorsal and anal fin function in bluegill sunfish Lepomis macrochirus: three
      dimensional kinematics during propulsion and maneuvering.
AB  - Dorsal and anal fins are median fins located above and below the centre of mass
      of fishes, each having a moment arm relative to the longitudinal axis.
      Understanding the kinematics of dorsal and anal fins may elucidate how these fins
      are used in concert to maintain and change fish body position and yet little is
      known about the functions of these fins. Using three synchronized high-speed
      cameras (500 frames s(-1)) we studied the three-dimensional kinematics of dorsal
      and anal fins during steady swimming (0.5-2.5 TL s(-1), where TL = total length)
      and during slow speed maneuvers (0.5 TL s(-1)). By digitizing points along every
      other fin ray in the soft-rayed portion of the fins we were able to determine not
      only the movement of the fin surface but also the curvature of individual fin
      rays and the resulting fin surface shape. We found that dorsal and anal fins
      begin oscillating, in phase, at steady swimming speeds above 1.0 TL s(-1) and
      that maximum lateral displacement of the trailing edge of the fins as well as fin
      area increase with increasing steady swimming speed. Differences in area, lateral
      displacement and moment arm between the dorsal and anal fin suggest that dorsal
      and anal fins produce balancing torques during steady swimming. During maneuvers,
      fin area is maximized and mean lateral excursion of both fins is greater than
      during steady swimming, with large variation among maneuvers. Fin surface shape
      changes dramatically during maneuvers. At any given point in time the spanwise
      (base to tip) curvature along fin rays can differ between adjacent rays,
      suggesting that fish have a high level of control over fin surface shape. Also,
      during maneuvers the whole surface of both dorsal and anal fins can be bent
      without individual fin rays exhibiting significant curvature.

PMID- 16000545
TI  - Cardioprotective effects of K ATP channel activation during hypoxia in goldfish
      Carassius auratus.
AB  - The activation of ATP-sensitive potassium (K ATP) ion channels in the heart is
      thought to exert a cardioprotective effect under low oxygen conditions, possibly
      enhancing tolerance of environmental hypoxia in aquatic vertebrates. The purpose
      of this study was to examine the possibility that hypoxia-induced activation of
      cardiac K ATP channels, whether in the sarcolemma (sarcK ATP) or mitochondria
      (mitoK ATP), enhances viability in cardiac muscle cells from a species highly
      tolerant of low oxygen environments, the goldfish Carassius auratus. During
      moderate hypoxia (6-7 kPa), the activation of sarcK ATP channels was indicated by
      a reduction in transmembrane action potential duration (APD). This response to
      hypoxia was mimicked by the NO-donor SNAP (100 micromol l(-1)) and the stable
      cGMP analog 8-Br-cGMP, but abolished by glibenclamide or l-NAME, an inhibitor of
      NO synthesis. The mitoK ATP channel opener diazoxide did not affect APD. Isolated
      ventricular muscle cells were then incubated under normoxic and hypoxic
      conditions. Cell viability was decreased in hypoxia; however, the negative
      effects of low oxygen were reduced during simultaneous exposure to SNAP, 8-Br
      cGMP, and diazoxide. The cardioprotective effect of diazoxide, but not 8-Br-cGMP,
      was reduced by the mitoK ATP channel blocker 5-HD. These data suggest that
      hypoxia-induced activation of sarcK ATP or mitoK ATP channels could enhance
      tolerance of low-oxygen environments in this species, and that sarcK ATP activity
      is increased through a NO and cGMP-dependent pathway.

PMID- 16000546
TI  - Ectothermy and endothermy: evolutionary perspectives of thermoprotection by HSPs.
AB  - Living organisms respond to heat exposure by selectively expressing heat shock
      proteins (HSPs). Accumulation of HSPs confers thermotolerance in cell cultures
      and in ectotherms and is an important component of the heat shock response. This
      response, however, has not been directly examined in relation to different
      ;thermal states', namely ectothermy vs endothermy. By using avian development as
      a model system for transition from ectothermy to endothermy, we show that, in
      contrast to the ectothermic state, in the endothermic state the organism is more
      resistant to heat but relies less on HSPs as a first-line thermoprotective
      mechanism. Moreover, intraspecific, real-time, in vivo measurements in
      genetically diverse fowl strains relate improvement of thermoresistance in
      endotherms to improved body temperature (Tb) regulation, with a concomitant delay
      in the expression of HSPs. The time course of this delay and the Tb at which it
      occurs imply that the ontogenetic and evolutionary pathways leading to improved
      thermoresistance may have followed two, apparently non-related, parallel routes-
      cellular and peripheral (non-cellular). In search of other cellular components
      that differentially participate in the heat shock response, we revealed a
      significant expression of fatty acid synthase (FAS) in heat-exposed endotherms
      but not in ectotherms.

PMID- 16000547
TI  - V-ATPase expression during development of Artemia franciscana embryos: potential
      role for proton gradients in anoxia signaling.
AB  - Under anoxia, Artemia franciscana embryos downregulate metabolic processes and
      approach an ametabolic state. Entrance into this quiescent state is accompanied
      by a profound acidification of the intracellular space, and more than two decades
      of research now clearly demonstrates that this acidification is critical to
      metabolic downregulation in anoxic embryos. However, the proximal mechanisms
      responsible for the pH shift remain largely unidentified. Here, we report
      evidence demonstrating expression of the V-ATPase in encysted embryos and present
      an argument for its involvement in the intracellular acidification induced by
      anoxia. We identified a single B-subunit cDNA sharing the greatest degree of
      sequence similarity with ;generalist-type' homologues from mammals (brain-type)
      and invertebrates. Quantitative analysis of B-subunit mRNA demonstrates
      differential expression throughout early development, and western blot analyses
      confirm the expression of at least six V-ATPase subunits in both heavy membranes
      and microsomal vesicles. The critical need for proton pumping during the anoxia
      tolerant stage of development is demonstrated by incubation with the V-ATPase
      inhibitor bafilomycin A1, which halts embryonic development. Importantly, net
      proton flux from V-ATPase-acidified compartments to the surrounding cytoplasm is
      likely under anoxia and may significantly contribute to the enigmatic
      acidification critical to quiescence.

PMID- 16000548
TI  - V-ATPase inhibition prevents recovery from anoxia in Artemia franciscana embryos:
      quiescence signaling through dissipation of proton gradients.
AB  - The metabolic downregulation critical for long-term survival of Artemia
      franciscana embryos under anoxia is mediated, in part, by a progressive
      intracellular acidification. However, very little is known about the mechanisms
      responsible for the pH transitions associated with exposure to, and recovery
      from, oxygen deprivation. In the present study, we demonstrate with 31P-NMR that
      incubation of intact embryos with the V-ATPase inhibitor bafilomycin A1 severely
      limits intracellular alkalinization during recovery from anoxia without affecting
      the restoration of cellular nucleotide triphosphate levels. Based on these data,
      it appears that oxidative phosphorylation and ATP resynthesis can only account
      for the first 0.3 pH unit alkalinization observed during aerobic recovery from
      the 1 pH unit acidification produced during 1 h of anoxia. The additional 0.7 pH
      unit increase requires proton pumping by the V-ATPase. Aerobic incubation with
      bafilomycin also suggests that V-ATPase inhibition alone is not enough to induce
      an acute dissipation of proton gradients under anoxia. In intact embryos, the
      dissipation of proton gradients and uncoupling of oxidative phosphorylation with
      carbonyl cyanide 3-chlorophenylhydrazone (CCCP) leads to an intracellular
      acidification similar to that seen after 1 h of anoxia. Subsequent exposure to
      anoxia, in the continued presence of CCCP, yields little additional
      acidification, suggesting that proton gradients are normally dissipated under
      anoxia. When combined with protons generated from net ATP hydrolysis, these data
      show that the dissipation of proton chemical gradients is sufficient to account
      for the reversible acidification associated with quiescence in these embryos.

PMID- 16000549
TI  - Sprint running: a new energetic approach.
AB  - The speed of the initial 30 m of an all-out run from a stationary start on a flat
      track was determined for 12 medium level male sprinters by means of a radar
      device. The peak speed of 9.46+/-0.19 m s(-1) (mean +/- s.d.) was attained after
      about 5 s, the highest forward acceleration (a(f)), attained immediately after
      the start, amounting to 6.42+/-0.61 m s(-2). During acceleration, the runner's
      body (assumed to coincide with the segment joining the centre of mass and the
      point of contact foot terrain) must lean forward, as compared to constant speed
      running, by an angle alpha = arctang/a(f) (g = acceleration of gravity). The
      complement (90-alpha) is the angle, with respect to the horizontal, by which the
      terrain should be tilted upwards to bring the runner's body to a position
      identical to that of constant speed running. Therefore, accelerated running is
      similar to running at constant speed up an ;equivalent slope' ES = tan(90-alpha).
      Maximum ES was 0.643+/-0.059. Knowledge of ES allowed us to estimate the energy
      cost of sprint running (C(sr), J kg(-1) m(-1)) from literature data on the energy
      cost measured during uphill running at constant speed. Peak Csr was 43.8+/-10.4 J
      kg(-1) m(-1); its average over the acceleration phase (30 m) was 10.7+/-0.59 J
      kg(-1) m(-1), as compared with 3.8 for running at constant speed on flat terrain.
      The corresponding metabolic powers (in W kg(-1)) amounted to 91.9+/-20.5 (peak)
      and 61.0+/-4.7 (mean).

PMID- 16000550
TI  - 2,2'-Dichlorobiphenyl decreases amplitude and synchronization of uterine
      contractions through MAPK1-mediated phosphorylation of GJA1 (connexin43) and
      inhibition of myometrial gap junctions.
AB  - The present study examined the hypothesis that inhibition of myometrial gap
      junctions through MAPK1-induced phosphorylation of GJA1 (connexin43) leads to
      inhibition of spontaneous phasic uterine contractions by 2,2'-dichlorobiphenyl
      (2,2'-DCB). Uterine strips from Gestation Day 10-pregnant rats exposed in muscle
      baths to 2,2'-DCB exhibited increased oscillatory frequency and decreased
      amplitude and synchronization of contractions. To assess effects on gap
      junctions, Lucifer yellow was injected into myometrial cells and transfer to
      adjacent cells was scored. After a 1-h treatment, 100 microM 2,2'-DCB decreased
      Lucifer yellow intercellular transfer in a concentration-dependent manner. The
      MAP2K1 inhibitor PD98059 increased percentage of dye transfer to adjacent
      myometrial cells from 18% in cultures exposed for 1 h to 100 microM 2,2'-DCB
      alone to 48% in cultures cotreated with 50 microM PD98059 and 100 microM 2,2'
      DCB. In contrast, the conventional PRKC inhibitor Go6976 (10 microM) had no
      significant effect on 2,2'-DCB-induced inhibition of dye transfer. Western
      blotting showed about a 4.5-fold increase in phosphorylation of GJA1 at S255, a
      MAPK1 site, after exposure to 100 microM 2,2'-DCB compared to untreated and
      solvent controls. However, there was no difference in phosphorylation of GJA1 at
      S368, a PRKC site. Cells treated with 2,2'-DCB increased phosphorylated MAPK1,
      implicating the increase of activation of MAPK1. Cotreatment with 100 microM 2,2'
      DCB and 5 microM PD98059 reversed 2,2'-DCB-induced modification of uterine
      contractions and increase of pGJA1(S255) in uterine strips. Therefore, this study
      suggests that 2,2'-DCB decreases amplitude and synchronization of uterine
      contractions mediated through MAPK1-mediated phosphorylation of GJA1 and
      subsequent inhibition of myometrial gap junctions.

PMID- 16000551
TI  - Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian
      primordial to primary follicle transition.
AB  - An important but poorly understood process in ovarian biology is the transition
      of the developmentally arrested primordial follicle to the developing primary
      follicle. Interactions between the epithelial and mesenchymal cells of the
      follicle are critical for the coordination of ovarian follicle development. The
      mesenchymal growth factor keratinocyte growth factor (KGF) (i.e., fibroblast
      growth factor-7) and the epithelial growth factor kit ligand (KITL) are known to
      interact to coordinate the growth of later-stage antral follicles. The hypothesis
      tested in the current study is that KGF acts as a mesenchymal factor to promote
      the primordial to primary follicle transition. A postnatal 4-day-old rat ovary
      organ culture system was used to investigate the actions of KGF. KGF treatment
      promoted 65% of follicles to undergo the primordial to primary follicle
      transition, but only 45% underwent development in control ovaries. Neutralizing
      antibody for KGF was found to attenuate the stimulatory action of KITL, but
      neutralizing antibody for KITL was not able to attenuate the stimulatory action
      of KGF. Further analysis demonstrated that KGF was found to stimulate the
      expression of KITL (i.e., mRNA levels) by granulosa cells. KITL in turn was found
      to stimulate the expression of KGF to create a positive feedback loop.
      Interestingly, KGF expression was localized to selected mesenchymal cells (i.e.,
      precursor theca cells) surrounding the developing primordial follicle.
      Observations suggest that developing granulosa cells of the primordial follicles
      produce KITL, which helps recruit precursor theca cells to the follicle; the
      thecal cells then produce KGF, which acts on the granulosa to amplify KITL
      expression and support primordial follicle development. KGF appears to be a
      mesenchymal factor that promotes the primordial to primary follicle transitions.

PMID- 16000552
TI  - Sertoli cell proliferation in the adult testis--evidence from two fish species
      belonging to different orders.
AB  - Germ cell survival and development critically depend on the cells' contact with
      Sertoli cells in the vertebrate testis. Fish and amphibians are different from
      mammals in that they show a cystic type of spermatogenesis in which a single germ
      cell clone is enclosed by and accompanied through the different stages of
      spermatogenesis by an accompanying group of Sertoli cells. We show that in
      maturing and adult testes from African catfish and Nile tilapia, Sertoli cell
      proliferation occurs primarily during spermatogonial proliferation, allowing the
      cyst-forming Sertoli cells to provide the increasing space required by the
      growing germ cell clone. In this regard, coincident with a dramatic increase in
      cyst volume and number of germ cells per cyst, in Nile tilapia, the number of
      Sertoli cells per cyst was strikingly increased from primary spermatogonia to
      spermatocyte cysts. In both African catfish and Nile tilapia, Sertoli cell
      proliferation is strongly reduced when germ cells have proceeded into meiosis,
      and stops in postmeiotic cysts. We conclude that Sertoli cell proliferation is
      the primary factor responsible for the increase in testis size and sperm
      production observed in teleost fish. In mammals, Sertoli cell proliferation in
      the adult testis is not observed under natural conditions. However, on the level
      of the individual spermatogenic cyst--similar to mammals--Sertoli cell
      proliferation ceases when germ cells have entered meiosis and when tight
      junctions are established between Sertoli cells. This suggests that fish are
      valid vertebrate models for studying Sertoli cell physiology.

PMID- 16000553
TI  - Radioimmunotherapy for colorectal cancer.

PMID- 16000554
TI  - Lysophosphatidic acid, a disintegrin and metalloprotease-17 and heparin-binding
      epidermal growth factor-like growth factor in ovarian cancer: the first word, not
      the last.

PMID- 16000555
TI  - Lost in translation: the future of cancer research?

PMID- 16000556
TI  - Overexpression of osteopontin is associated with more aggressive phenotypes in
      human non-small cell lung cancer.
AB  - PURPOSE: The extracellular matrix (ECM) molecule osteopontin is implicated in
      many pathologic processes, including inflammation, cell proliferation, ECM
      invasion, tumor progression, and metastasis. The present study evaluated the
      clinical and biological importance of osteopontin in human lung cancer.
      EXPERIMENTAL DESIGN AND RESULTS: Tissue microarrays derived from non-small cell
      lung cancer (NSCLC) patients were analyzed immunohistochemically. Osteopontin
      protein expression was observed in 64.5% (205 of 318) of primary tumors and 75.5%
      (108 of 143) of lymph node metastases, but in only 27.9% (12 of 43) of normal
      appearing bronchial epithelial and pulmonary tissues. Osteopontin expression was
      associated with tumor growth, tumor staging, and lymph node invasion. In vitro
      osteopontin enhanced ECM invasion of NSCLC cells, and an osteopontin antibody
      abolished this effect. We further analyzed osteopontin levels in circulating
      plasma derived from 158 patients with NSCLC, 54 patients of benign pulmonary
      disease, and 25 healthy donors, and found that the median osteopontin levels for
      the three groups were 319.1, 161.6, and 17.9 ng/mL, respectively. CONCLUSIONS:
      Overexpression of osteopontin is common in primary NSCLC and may be important in
      the development and progression of the cancer. Osteopontin levels in the plasma
      may serve as a biomarker for diagnosing or monitoring patients with NSCLC.

PMID- 16000557
TI  - Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer.
AB  - PURPOSE: Prostate cancer eventually recurs during androgen deprivation therapy
      despite castrate levels of serum androgens. Expression of androgen receptor and
      androgen receptor-regulated proteins suggests androgen receptor activation in
      recurrent prostate cancer. Many groups have pursued mechanisms of ligand
      independent androgen receptor activation but we found high levels of testicular
      androgens in recurrent prostate cancer tissue using RIA. EXPERIMENTAL DESIGNS:
      Prostate specimens from 36 men were procured preserving blood flow to prevent
      ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from
      18 men whose cancer recurred locally during androgen deprivation therapy and
      androgen-stimulated benign prostate specimens from 18 men receiving no hormonal
      treatments were studied. Tissue levels of testosterone and dihydrotestosterone
      were measured in each specimen using liquid chromatography/electrospray tandem
      mass spectrometry. Testosterone and dihydrotestosterone levels were compared with
      clinical variables and treatment received. RESULTS: Testosterone levels were
      similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated
      benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P=0.30).
      Dihydrotestosterone levels decreased 91% in recurrent prostate cancer (1.25
      pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g
      tissue; Wilcoxon two-sided, P < 0.0001) although dihydrotestosterone levels in
      most specimens of recurrent prostate cancer were sufficient for androgen receptor
      activation. Testosterone or dihydrotestosterone levels were not related to
      metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P
      > 0.2). CONCLUSIONS: Recurrent prostate cancer may develop the capacity to
      biosynthesize testicular androgens from adrenal androgens or cholesterol. This
      surprising finding suggests intracrine production of dihydrotestosterone and
      should be exploited for novel treatment of recurrent prostate cancer.

PMID- 16000558
TI  - The expression of functional chemokine receptor CXCR4 is associated with the
      metastatic potential of human nasopharyngeal carcinoma.
AB  - PURPOSE: Chemokine receptors are implicated in metastasis of several malignant
      tumors. This study was done to evaluate the contribution of chemokine receptors
      CXCR4 and CCR7 to metastasis of human nasopharyngeal carcinoma. EXPERIMENTAL
      DESIGN: Reverse transcription-PCR, immunohistochemistry, and flow cytometry were
      used to evaluate mRNA and protein expression of CXCR4 and CCR7 in nasopharyngeal
      carcinoma tumor tissues and cell lines. Chemotaxis assays were used to evaluate
      the function of CXCR4 in nasopharyngeal carcinoma cells. Antisense CXCR4 was used
      to inhibit receptor expression and to block metastasis of human nasopharyngeal
      carcinoma cells in vivo in athymic mice. RESULTS: CXCR4 protein was detected in
      tumor cells in 31 of 40 primary human nasopharyngeal carcinoma and in 13 of 15
      lymph node metastases. CXCR4 transcripts were detected in eight CXCR4 protein
      positive primary nasopharyngeal carcinoma tissues and seven nasopharyngeal
      carcinoma cell lines tested. On the other hand, the transcripts for CCR7 were
      detected only in four primary nasopharyngeal carcinoma tissues and in none of the
      nasopharyngeal carcinoma cell lines. In functional experiments, metastatic
      nasopharyngeal carcinoma cell lines that expressed high levels of CXCR4 were
      found to migrate in response to the CXCR4 ligand SDF-1alpha. Transfection of
      antisense CXCR4 in metastatic nasopharyngeal carcinoma cells inhibited the
      expression of CXCR4 and SDF-1alpha-induced cell migration in vitro and reduced
      the capacity of the tumor cells to form metastasis in the lungs and lymph nodes
      when injected in athymic mice. CONCLUSION: The expression of functional CXCR4 but
      not CCR7 is correlated with the metastatic potential of human nasopharyngeal
      carcinoma cells. Therefore, CXCR4 may be considered as a potential target for the
      prevention of nasopharyngeal carcinoma metastasis.

PMID- 16000559
TI  - Hematogenous micrometastases in osteosarcoma patients.
AB  - Bone marrow and peripheral blood samples from 60 patients with suspected bone
      sarcoma were examined for the presence and number of micrometastatic osteosarcoma
      cells by a sensitive immunomagnetic detection assay, using in parallel two
      osteosarcoma-associated antibodies. Forty-nine of the patients had osteosarcoma,
      and of these, as many as 31 (63%) had tumor cells in bone marrow, in many cases
      with a high number of cells. Only four (8%) were positive also in blood. None of
      38 control bone marrow samples were positive, including 11 from patients with
      suspected bone sarcoma at time of sampling who later were found not to have
      osteosarcoma. Fifteen of 28 patients without overt metastases at primary
      diagnosis (54%) were positive, 12 of whom had localized high-grade primary tumors
      in the extremity. Four of these have relapsed compared with none of 10 negative
      patients. In the group of 22 patients with extremity localized nonmetastatic
      osteosarcoma, information was available on the histologic response to
      preoperative chemotherapy in 15 patients. None of the three patients in the bone
      marrow-negative group who had a poor response to chemotherapy have relapsed,
      whereas two of the four poor responders in the bone marrow-positive cohort are
      dead of disease. Among 12 patients with overt metastasis at primary diagnosis, 11
      (92%) were positive in bone marrow with a very high number of osteosarcoma cells.
      The immunomagnetically isolated cells were further characterized by the use of
      fluorescent latex microparticles with surface-bound antibodies targeting
      different membrane markers. Moreover, in cases with numerous osteosarcoma cells
      in bone marrow attempts to grow the selected cells in vitro were successful in
      two of eight attempts, and in two of five cases, isolated cells produced tumors
      with osteosarcoma characteristics in nude mice. In conclusion, already at primary
      diagnosis, a very high fraction of osteosarcoma patients had malignant cells in
      bone marrow, and a correlation between the presence of tumor cells, clinical
      stage, and disease progression was found. The data show the clinical potential of
      this immunomagnetic method. Attempts to subgroup osteosarcoma patients for more
      individualized treatment based on the presence of micrometastatic cells should be
      studied in a larger cohort of patients.

PMID- 16000560
TI  - Expression and growth dependency of the insulin-like growth factor I receptor in
      craniopharyngioma cells: a novel therapeutic approach.
AB  - Craniopharyngioma is a rare benign intracranial epithelial tumor that, however,
      often recurs and sometimes kills the affected patients, one-third of which are
      children. In many cases, the patients acquire growth hormone deficiency and
      postoperatively need substitution. Generally, growth hormone promotes local
      release of insulin-like growth factor I (IGF-I), which in turn activates the IGF
      I receptor (IGF-IR) if present. Together, these circumstances raise the question
      whether IGF-IR may be involved in craniopharyngioma growth. To address this
      issue, we analyzed phenotypically well-characterized primary low-passage
      craniopharyngioma cell lines from nine different patients for IGF-IR expression
      and IGF-I dependency. Two of the cell lines showed no/very low expression of the
      receptor and was independent on IGF-I, whereas five cell lines exhibited a strong
      expression and was clearly contingent on IGF-I. The two remaining cell lines had
      low receptor expression and IGF-I dependency. Upon treatment with an IGF-IR
      inhibitor, cells with high IGF-IR expression responded promptly with decreased
      Akt phosphorylation followed by growth arrest. These responses were not seen in
      cells with no/very low receptor expression. Growth of cell lines with low IGF-IR
      expression was only slightly affected by IGF-IR inhibition. Taken together, our
      data suggest that IGF-IR may be involved in the growth of a subset of
      craniopharyngiomas and points to the possibility of the involvement of IGF-IR
      inhibitors as a treatment modality to obtain complete tumor-free conditions
      before growth hormone substitution.

PMID- 16000561
TI  - Epigenetic down-regulation of CDKN1C/p57KIP2 in pancreatic ductal neoplasms
      identified by gene expression profiling.
AB  - PURPOSE: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an
      increasingly identified precursor to infiltrating ductal adenocarcinoma. Although
      our knowledge of the clinical and pathologic features of IPMNs is increasing, the
      molecular mechanisms underlying these neoplasms remain poorly understood.
      EXPERIMENTAL DESIGNS: To provide further insight into the molecular pathobiology
      of IPMNs, global expression profiling was done to determine genes that are
      inactivated/down-regulated in IPMNs using oligonucleotide microarrays
      (Affymetrix). RESULTS: In total, 300 unique transcripts (217 known genes) were
      identified as highly underexpressed in 12 IPMNs (<10-fold lower and P < 0.05)
      compared with five normal pancreatic ductal epithelium samples obtained by laser
      capture microdissection. The differential expression of a selection of genes was
      confirmed using reverse-transcription PCR. One of the genes underexpressed at
      both the transcriptional and protein level in a significant proportion of IPMNs
      was the cyclin-dependent kinase inhibitor, CDKN1C/p57KIP2. CDKN1C expression was
      also decreased in many pancreatic cancer cell lines and was restored following
      treatment with a DNA methylation inhibitor (5-aza-2'-deoxycitidine) or, more
      potently, with a histone deacetylase inhibitor (trichostatin A). Partial
      methylation of the CDKN1C promoter CpG island was found in most, but not all,
      pancreatic cancer cell lines with reduced CDKN1C expression, and was also
      detectable in IPMNs. Furthermore, a subset of pancreatic cancers showed complete
      hypomethylation of LIT1, an imprinting control region important for the
      regulation of CDKN1C expression. Complete hypomethylation in these cancers was
      the result of deletion of the methylated LIT1 allele at 11p15.5 rather than loss
      of imprinting. CONCLUSIONS: These findings suggest that CDKN1C is commonly down
      regulated in pancreatic ductal neoplasms through a combination of promoter
      hypermethylation, histone deacetylation, and loss of the maternal allele
      expressing CDKN1C.

PMID- 16000562
TI  - A homozygous mutation in MSH6 causes Turcot syndrome.
AB  - Heterozygous mutations in one of the DNA mismatch repair genes cause hereditary
      nonpolyposis colorectal cancer (MIM114500). Turcot syndrome (MIM276300) has been
      described as the association of central nervous system malignant tumors and
      familial colorectal cancer and has been reported to be both a dominant and
      recessive disorder. Homozygous and compound heterozygous mutations in APC, MLH1,
      MSH2, and PMS2 genes have been reported in five families. Here we describe a
      nonconsanguineous Pakistani family, including a son with lymphoma and colorectal
      cancer diagnosed at ages 5 and 8, respectively, and an 8-year-old daughter with
      glioblastoma multiforme. Both children had features of neurofibromatosis type 1
      including atypical cafe au lait spots and axillary freckling without a family
      history consistent with neurofibromatosis type 1, familial adenomatous polyposis,
      or hereditary nonpolyposis colorectal cancer. Mutational analysis was done for
      MLH1, MSH2, and MSH6 using denaturing high-performance liquid chromatography and
      sequencing of a blood sample from the daughter. A novel homozygous single base
      insertion mutation was identified (3634insT) resulting in a premature stop at
      codon 1,223 in exon 7 of the MSH6 gene. Both parents were found to be
      heterozygous for the 3634insT mutation. Microsatellite instability testing showed
      instability in the glioblastoma sample. We report here the first identification
      of a homozygous mutation in MSH6 in a family with childhood-onset brain tumor,
      lymphoma, colorectal cancer, and neurofibromatosis type 1 phenotype. Our findings
      support a role for MSH6 in Turcot syndrome and are consistent with an autosomal
      recessive mode of inheritance.

PMID- 16000563
TI  - Effect of low glutamine/glucose on hypoxia-induced elevation of hypoxia-inducible
      factor-1alpha in human pancreatic cancer MiaPaCa-2 and human prostatic cancer DU
      145 cells.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Tumor microenvironment is characterized by
      regions of fluctuating and chronic hypoxia, low extracellular pH, and nutrient
      depletion. Although it is well known that hypoxia stimulates the accumulation of
      hypoxia-inducible factor-1alpha (HIF-1alpha), the role of low extracellular pH
      and nutrient depletion on hypoxia up-regulation of HIF-1alpha is not well known.
      In this study, human pancreatic cancer MiaPaCa-2 and human prostatic cancer DU
      145 cells were exposed to hypoxia in the presence or absence of glucose,
      glutamine, and/or pyruvate. RESULTS: We observed that low glucose and low
      glutamine, but not low pyruvate, effectively suppressed the elevation of HIF
      1alpha level during hypoxia (0.1-1% oxygen). Deprivation of glutamine or glucose
      inhibited the accumulation of HIF-1alpha in the presence of MG-132, a protease
      inhibitor, regardless of oxygen tensions. Data from reverse transcription-PCR
      analysis revealed that the levels of HIF-1alpha mRNA were not significantly
      changed at different concentrations of glutamine or glucose under hypoxia. The
      amount of HIF-1alpha suppression was proportional to protein synthesis
      inhibition. CONCLUSIONS: Our data suggest that glutamine or glucose deprivation
      inhibits the accumulation of HIF-1alpha under hypoxic conditions by disrupting
      translational processes rather than transcriptional or proteasomal degradation
      processes.

PMID- 16000564
TI  - Increased expression and activity of CDC25C phosphatase and an alternatively
      spliced variant in prostate cancer.
AB  - Alterations in the control of cell cycle progression have been implicated in a
      wide variety of malignant neoplasms, including prostate cancer. CDC25
      phosphatases belong to the tyrosine phosphatase family and play a critical role
      in regulating cell cycle progression by dephosphorylating cyclin-dependent
      kinases at inhibitory residues. CDC25C plays an important role in the G2-M
      transition by activating Cdc2/Cyclin B1 complexes. To determine whether CDC25C
      activity is altered in prostate cancer, we have examined the expression of CDC25C
      and an alternatively spliced variant in human prostate cancer samples and cell
      lines. CDC25C protein is up-regulated in prostate cancer in comparison with
      normal prostate tissue and is present almost exclusively in its active
      dephosphorylated form. Expression of a biologically active alternatively spliced
      CDC25C isoform is also increased in prostate cancer and expression of
      alternatively spliced CDC25C is correlated to occurrence of biochemical (prostate
      specific antigen) recurrence. We have also developed a quantitative reverse
      transcriptase-PCR analysis of Ki-67 expression as a method of measuring
      proliferative activity in prostate cancer from RNA samples. Based on this
      analysis of Ki67 expression, some but not all of this increase in CDC25C and its
      alternatively spliced variants is correlated with increased proliferation in
      prostate cancer. This data suggests that CDC25C might play an important role in
      prostate cancer progression and could be used to monitor and predict the
      aggressiveness of this disease.

PMID- 16000565
TI  - Identification of a novel homozygous deletion region at 6q23.1 in
      medulloblastomas using high-resolution array comparative genomic hybridization
      analysis.
AB  - PURPOSE: The aim of this study is to comprehensively characterize genome copy
      number aberrations in medulloblastomas using high-resolution array comparative
      genomic hybridization. EXPERIMENTAL DESIGN: High-density genomic arrays
      containing 1,803 BAC clones were used to define recurrent chromosomal regions of
      gains or losses throughout the whole genome of medulloblastoma. A series of 3
      medulloblastoma cell lines and 16 primary tumors were investigated. RESULTS: The
      detected consistent chromosomal aberrations included gains of 1q21.3-q23.1
      (36.8%), 1q32.1 (47.4%), 2p23.1-p25.3 (52.6%), 7 (57.9%), 9q34.13-q34.3 (47.4%),
      17p11.2-q25.3 (89.5%), and 20q13.31-q13.33 (42.1%), as well as losses of 3q26.1
      (57.9%), 4q31.23-q32.3 (42.1%), 6q23.1-25.3 (57.9%), 8p22-23.3 (79%), 10q24.32
      26.2 (57.9%), and 16q23.2-q24.3 (63.2%). One of the most notable aberrations was
      a homozygous deletion on chromosome 6q23 in the cell line DAOY, and single copy
      loss on 30.3% primary tumors. Further analyses defined a 0.887 Mbp minimal region
      of homozygous deletion at 6q23.1 flanked by markers SHGC-14149 (6q22.33) and SHGC
      110551 (6q23.1). Quantitative reverse transcription-PCR analysis showed complete
      loss of expression of two genes located at 6q23.1, AK091351 (hypothetical protein
      FLJ34032) and KIAA1913, in the cell line DAOY. mRNA levels of these genes was
      reduced in cell lines D283 and D384, and in 50% and 70% of primary tumors,
      respectively. CONCLUSION: Current array comparative genomic hybridization
      analysis generates a comprehensive pattern of chromosomal aberrations in
      medulloblastomas. This information will lead to a better understanding of
      medulloblastoma tumorigenesis. The delineated regions of gains or losses will
      indicate locations of medulloblastoma-associated genes. A 0.887 Mbp homozygous
      deletion region was newly identified at 6q23.1. Frequent detection of reduced
      expression of AK091351 and KIAA1913 genes implicates them as suppressors of
      medulloblastoma tumorigenesis.

PMID- 16000566
TI  - Spontaneous regression of high-grade cervical dysplasia: effects of human
      papillomavirus type and HLA phenotype.
AB  - PURPOSE: Persistent infection with oncogenic human papillomaviruses (HPV) plays a
      central etiologic role in the development of squamous carcinomas of the cervix
      and their precursor lesions, cervical intraepithelial neoplasias (CIN). We
      carried out a prospective observational cohort study evaluating known,
      quantifiable prognostic variables of clinical behavior in women with high-grade
      cervical lesions. EXPERIMENTAL DESIGN: Our study cohort included healthy women
      with high-grade cervical lesions (CIN2/3) with residual visible lesions after
      colposcopically directed biopsy. We prospectively followed 100 women over 15
      weeks before standard resection. HPV typing was done using PCR and a reverse line
      blot detection method. RESULTS: The rate of spontaneous histologic regression,
      defined as (CIN1 or less at resection) was 28%. The overall rate of HPV infection
      was 100%. HPV16 was identified in 68% of the lesions. Women with HPV16 only were
      significantly less likely to regress, compared with women with HPV types other
      than HPV16 (odds ratio, 0.342; 95% confidence interval, 0.117-0.997; P = 0.049).
      In the cohort with HPV16 only, patients who had an HLA*A201 allele had similar
      outcomes to those who did not carry A201. However, among patients with HPV types
      other than HPV16, the HLA*A201 allele interaction was significant; patients with
      HLA*A201 were the least likely to resolve. CONCLUSIONS: CIN2/3 lesions associated
      with HPV16 alone are significantly less likely to resolve spontaneously than
      those caused by other types. Interactions among HPV type, HLA type, and
      regression rate support a role for HLA-restricted HPV-specific immune responses
      in determining disease outcome.

PMID- 16000567
TI  - Assessment of the transcriptional activity of p53 improves the prediction of
      recurrence in superficial transitional cell carcinoma of the bladder.
AB  - PURPOSE: To investigate the value of p53 functional analysis of separated alleles
      in yeast (FASAY) as a witness of p53/p21 pathway alteration and as a predictor of
      recurrence in superficial transitional cell carcinomas. EXPERIMENTAL DESIGN: p53
      transcriptional activity was prospectively analyzed in 52 newly diagnosed
      transitional cell carcinoma using FASAY competent for the transactivation of p21
      and bax promoters. TP53 and p21 gene expression was quantified by real-time PCR,
      and expression of corresponding proteins was assessed by immunohistochemistry. In
      addition to tumor stage and grade, the predictive value of FASAY, real-time PCR,
      and immunohistochemistry for tumor recurrence was assessed by Cox survival
      analysis. RESULTS: A total (p21 and bax) or partial (bax only) loss of
      transcriptional activity was observed in 15 of 52 (29%) and 4 of 52 (7.7%) cases,
      respectively, a partial loss being consistently associated with R283H mutation.
      p53 nuclear overexpression grossly overestimated (approximately 40%) or
      underestimated (approximately 10%) the true incidence of p53 transcriptional
      abnormalities, especially in Ta-T1 grade 1 to 2 tumors. Loss of p21
      transactivation significantly correlated with decreased p21 gene expression and
      lack of expression of p21 (P = 0.001). FASAY had a better predictive value for
      recurrence than p53 immunohistochemistry (Cox hazard ratio, 6.57 versus 3.95; P =
      0.0002 versus 0.019, respectively), whereas neither p21 immunohistochemistry
      (hazard ratio, 1.9; P = 0.29) nor TP53 or p21 gene expression were significant
      predictors of recurrence. The prognostic difference between FASAY and p53
      immunohistochemistry was maintained in the subgroup of Ta-T1 grade 3 tumors.
      CONCLUSIONS: FASAY is a valuable surrogate marker for assessing p53/p21 pathway
      alteration and predicts transitional cell carcinoma recurrence better than p53
      immunohistochemistry.

PMID- 16000568
TI  - Isochromosome 17q is a negative prognostic factor in poor-risk childhood
      medulloblastoma patients.
AB  - BACKGROUND: Medulloblastomas are the most common primary malignant childhood
      intracranial neoplasms. Patients are currently sorted into three risk groups
      based on clinical criteria: standard, poor, and infant (<18 months old). We
      hypothesized that genetic copy number aberrations (CNA) predict prognosis and
      would provide improved criteria for predicting outcome. METHODS: DNA from 35
      medulloblastoma patients from four Children's Cancer Group trials was analyzed by
      comparative genomic hybridization to determine CNAs. The genetic alterations were
      evaluated using statistical and cluster analyses. RESULTS: The most frequent CNAs
      were gains on 17q, 7, 1q, and 7q and losses on 17p, 10q, X, 16q, and 11q.
      Amplification at 5p15.1-p15.3 was also detected. Isochromosome 17q (i(17)(q10))
      was associated with poor overall survival (P = 0.03) and event-free survival (P =
      0.04) independent of poor risk group classification. Age <3 tended to be
      associated with <3 CNAs (P = 0.06). Unsupervised cluster analysis sorted the
      study patients into four subgroups based on CNAs. Supervised analysis using the
      program Significance Analysis of Microarrays (SAM) quantitatively validated those
      CNAs identified by unsupervised clustering that significantly distinguished among
      the four subgroups. CONCLUSIONS: Medulloblastomas are genetically heterogeneous
      and can be categorized into separate genetic subgroups by their CNAs using
      unsupervised cluster analysis and SAM. i(17)(q10) was a significant independent
      negative prognostic factor. Infant medulloblastomas may be a distinct genetic
      subset from those of older patients.

PMID- 16000569
TI  - A meta-analysis on the interaction between HER-2 expression and response to
      endocrine treatment in advanced breast cancer.
AB  - PURPOSE: Experimental data suggest a complex cross-talk between HER-2 and
      estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be
      less responsive to certain endocrine treatments. Clinical data, however, have
      been conflicting. We have conducted a meta-analysis on the interaction between
      the response to endocrine treatment and the overexpression of HER-2 in metastatic
      breast cancer. EXPERIMENTAL DESIGN: Studies have been identified by searching the
      Medline, Embase, and American Society of Clinical Oncology abstract databases.
      Selection criteria were (a) metastatic breast cancer, (b) endocrine therapy (any
      line of treatment), and (c) evaluation of HER-2 expression (any method). For each
      study, the relative risk for treatment failure for HER-2-positive over HER-2
      negative patients with 95% confidence interval was calculated as an estimate of
      the predictive effect of HER-2. Pooled estimates of the relative risk were
      computed by the Mantel-Haenszel method. RESULTS: Twelve studies (n = 2,379
      patients) were included in the meta-analysis. The overall relative risk was 1.42
      (95% confidence interval, 1.32-1.52; P < 0.00001; test for heterogeneity =
      0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95%
      confidence interval, 1.20-1.48; P < 0.00001; test for heterogeneity = 0.97); for
      studies involving other hormonal drugs, a pooled relative risk of 1.49 (95%
      confidence interval, 1.36-1.64; P < 0.00001; test for heterogeneity = 0.08) was
      estimated. A second meta-analysis limited to tumors that were either estrogen
      receptor positive, estrogen receptor unknown, or estrogen receptor
      negative/progesterone receptor positive yielded comparable results. CONCLUSIONS:
      HER-2-positive metastatic breast cancer is less responsive to any type of
      endocrine treatment. This effect holds in the subgroup of patients with positive
      or unknown steroid receptors.

PMID- 16000570
TI  - Association of GSTP1 polymorphism and survival for esophageal cancer.
AB  - PURPOSE: Activity of glutathione S-transferase (GST) is associated with
      detoxification of xenobiotics and the maintenance of cell viability. Genetically
      variant GSTs produce different enzymatic activities. The clinical significance of
      this variation is still puzzling. We investigated whether genetic polymorphisms
      of GST including GSTP1, GSTM1, and GSTT1 affect survival among esophageal cancer
      patients. EXPERIMENTAL DESIGN: From 1996 to 2002, 233 patients with
      pathologically proven esophageal cancer were recruited from the Department of
      Surgery, National Taiwan University Hospital. GST genotypes, including GSTT1,
      GSTM1, and GSTP1, were determined by PCR or PCR-RFLP. The influence of the
      genetic polymorphisms on patient survival was estimated using the method of
      Kaplan-Meier survival function and Cox proportional hazards models. RESULTS: The
      mean survival times (months) of the GSTP1 Ile/Ile, Ile/Val, and Val/Val were 11,
      10, and 7, respectively (P < 0.05). The more the patients carried GSTP1 variant
      Val alleles, the poorer the survival rate (adjusted hazard ratio, 1.36; 95%
      confidence interval, 1.01-1.84; Ptrend = 0.045). In contrast, no association of
      GSTT1 or GSTM1 genotypes with survival rate was noted. CONCLUSION: The presence
      of the GSTP1 variant allele (Val) is associated with a poorer prognosis of
      esophageal cancer.

PMID- 16000571
TI  - Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall
      patient survival.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2) expression in human colorectal cancer and
      adenoma tissue seems to be higher than in normal mucosa. However, data about the
      relation between COX-2 expression and patient survival are inconclusive as yet.
      Therefore, we studied COX-2 expression in surgery tissue and survival time in a
      cohort of 747 colorectal cancer patients. EXPERIMENTAL DESIGN: Surgical specimens
      of primary colorectal cancer from 747 individuals were immunostained for COX-2
      and evaluated under a transmission light microscope. COX-2 expression was scored
      according to intensity and extent of staining, resulting in the COX-2
      immunoreactivity score (IRS-COX2). All possible cutoff points for IRS-COX2 were
      analyzed for a relation between COX-2 expression and patient survival. RESULTS:
      Both univariable and multivariable analysis have shown that the COX-2 expression
      in human tumor epithelial cells was unrelated to overall patient survival and to
      disease-free survival, irrespectively of the cutoff point for IRS-COX2. The
      survival rates for 1, 3, 5, and 10 years were 81.0%, 66.8%, 60.2%, and 49.8%
      (median: 117.3 months; 95% confidence interval, 102.3-132.0), respectively. In
      the multivariable analysis, only node and metastasis were significantly related
      to overall patient survival. Similar results were obtained when stage IV and
      rectal cancer patients were excluded from the analysis. CONCLUSIONS: COX-2
      expression in tumor epithelial cells does not seem to be related to survival of
      colorectal cancer patients. Besides COX-2, there are several targets, such as the
      peroxisome proliferator-activated receptors, that are involved in carcinogenesis
      and may be modulated by nonsteroidal anti-inflammatory drugs. Further studies are
      needed to determine their prognostic relevance.

PMID- 16000572
TI  - 2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of
      disease in patients with prostate-specific antigen relapse after radical
      prostatectomy.
AB  - EXPERIMENTAL DESIGN: Retrospective cohort study in 91 patients with prostate
      specific antigen (PSA) relapse following prostatectomy, imaged with 2-[18F]fluoro
      2-deoxyglucose positron emission tomography (FDG-PET) in a tertiary care cancer
      center between February 1997 and March 2003. Comparison was made with magnetic
      resonance imaging (n = 64), bone scan (n = 56), and computed tomography (n = 37).
      The standard of reference included biopsy or clinical and imaging follow-up. We
      calculated sensitivity and specificity of PET and correlated PET findings with
      PSA values, other clinical parameters, and conventional imaging, when available.
      RESULTS: PET was true positive in 28 of 91 (31%) patients, showing isolated
      disease in the prostate bed (n = 3) or metastatic disease with (n = 2) or without
      (n = 23) simultaneous disease in the prostate bed. In detail, PET identified
      lesions in the prostate bed (n = 5, all true positives), bones (n = 22; 20 true
      positives, 2 false positives), lymph nodes (n = 7; 6 true positives, 1 likely
      false positive), and one liver metastasis. Mean PSA was higher in PET-positive
      than in PET-negative patients (9.5 +/- 2.2 versus 2.1 +/- 3.3 ng/mL). PSA of 2.4
      ng/mL and PSA velocity of 1.3 ng/mL/y provided the best tradeoff between
      sensitivity (80%; 71%) and specificity (73%; 77%) of PET in a receiver operating
      curve analysis. Combination with other clinical parameters in a multivariate
      analysis did not improve disease prediction. There were only two patients in whom
      other imaging studies showed isolated local recurrence or metastatic disease.
      CONCLUSIONS: FDG-PET detected local or systemic disease in 31% of patients with
      PSA relapse referred for this test. There is a link to tumor burden and tumor
      biology in that the probability for disease detection increased with PSA levels.

PMID- 16000573
TI  - FAS/FAS ligand ratio: a marker of oxaliplatin-based intrinsic and acquired
      resistance in advanced colorectal cancer.
AB  - PURPOSE: Oxaliplatin-5-fluorouracil combinations have increased responses in
      first-line therapy up to 40% in advanced colorectal cancer. Unfortunately, those
      patients who will respond are unknown and initially sensitive patients become
      rapidly resistant to current therapies. FAS (CD95) and FAS ligand (FASL; CD95L)
      have been implicated in chemosensitivity through leading to apoptosis in response
      to DNA-damaging drugs. Whereas the proapoptotic role of FAS and FASL is well
      characterized, the function of their soluble forms as predictors of
      chemosensitivity remains unknown. PATIENTS AND METHODS: Blood samples were
      obtained from 68 patients with advanced colorectal cancer who received
      oxaliplatin-5-fluorouracil combinations in first-line therapy. Computed
      tomographic scans were done every 3 months and responses were evaluated by
      Response Evaluation Criteria in Solid Tumors criteria. ELISA soluble FAS and
      soluble FASL analysis were done before treatment and every 3 months until disease
      progression. Ratios between soluble FAS and soluble FASL were established and its
      values and variations through time were related to treatment responses. RESULTS:
      We found a significant increase in soluble FAS levels and a significant decrease
      in FASL at 3 months compared with baseline (13.2 versus 10.02 ng/mL; P=0.0001;
      0.07 versus 0.14 ng/mL; P=0.007, respectively). A significant increase in the
      soluble FASL levels up to 9 months (fourth to fifth extractions; 0.26 ng/mL) of
      therapy compared with first to third extractions (0.11 ng/mL; P=0.003) was also
      found. A random effect regression statistical model determined that >1.2-fold
      increase in soluble FAS/soluble FASL ratio was a marker of chemosensitivity (P =
      0.001). CONCLUSIONS: These data strongly indicate that an increment of soluble
      FAS/soluble FASL ratio after treatment could be an excellent marker of
      chemosensitivity in colorectal cancer. On the other hand, a decreased ratio after
      treatment can be a predictor of chemoresistance despite an initial response.

PMID- 16000574
TI  - A haplotype analysis of HER-2 gene polymorphisms: association with breast cancer
      risk, HER-2 protein expression in the tumor, and disease recurrence in Korea.
AB  - PURPOSE: A single-nucleotide polymorphism (SNP) in codon 655 of HER-2 has been
      extensively studied with inconclusive results. The purpose of this study was to
      investigate the association between common variants of HER-2 and breast cancer
      risk, HER-2 expression, and survival using a haplotype-based stepwise approach.
      EXPERIMENTAL DESIGN: Twenty-nine SNPs listed in the National Center for
      Biotechnology Information database were screened to identify novel polymorphisms
      of HER-2 gene in 90 healthy Korean women. Six of 29 SNPs were polymorphic and had
      greater than 10% of minor allele frequencies. Using these six SNPs, linkage
      disequilibrium and haplotype patterns were characterized. We tested association
      between the haplotypes and breast cancer in a large case-control study (n=1,039
      cases and 995 controls). Six-hundred two breast cancer patients with follow-up at
      least 24 months were analyzed for outcome in relation to haplotype. Expression of
      HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive
      breast cancer. RESULTS: All six SNPs showed a strong linkage disequilibrium
      pattern and were considered to belong to one haplotype block. Two haplotype
      tagging SNPs (I655V and P1170A) for three common haplotypes (>5%) were genotyped
      in cases and controls. The haplotypes and individual SNPs were not associated
      with breast cancer risk. In patients with at least one copy of haplotype I (the
      most common haplotype), HER-2 expression was 1.5 times higher (P = 0.009) and the
      prognosis was worse (P = 0.032) compared with patients without having that
      haplotype. CONCLUSIONS: Our results suggest that the currently identified genetic
      polymorphisms of HER-2 are not associated with an increased risk of breast cancer
      in Korean women, whereas one haplotype does affect protein expression of the
      tumor and disease outcome.

PMID- 16000575
TI  - Clinical significance of heparin-binding epidermal growth factor-like growth
      factor and a disintegrin and metalloprotease 17 expression in human ovarian
      cancer.
AB  - PURPOSE: Lysophosphatidic acid, which is enriched in the peritoneal fluid of
      ovarian cancer patients, plays a key role in the progression of ovarian cancer.
      Lysophosphatidic acid can generate epidermal growth factor receptor (EGFR) signal
      transactivation involving processing of EGFR ligands by ADAM (a disintegrin and
      metalloprotease) family metalloproteases. We aimed to investigate the clinical
      significance of EGFR ligands and ADAM family in the lysophosphatidic acid-induced
      pathogenesis of ovarian cancer. EXPERIMENTAL DESIGN: We examined the expression
      of EGFR ligands and ADAM family members in 108 patients with normal ovaries or
      ovarian cancer, using real-time PCR, immunohistochemistry, and in situ
      hybridization, and analyzed the clinical roles of these molecules. Statistical
      analyses of these data were done using the Mann-Whitney test, Kaplan-Meier
      method, or Spearman's correlation analysis. RESULTS: Large differences in
      expression were found for heparin-binding EGF-like growth factor (HB-EGF) and
      other EGFR ligands and for ADAM 17 and other ADAM family members. HB-EGF
      expression was significantly increased in advanced ovarian cancer compared with
      that in normal ovaries (P < 0.01). HB-EGF expression was significantly associated
      with the clinical outcome (P < 0.01). ADAM 17 expression was significantly
      enhanced in both early and advanced ovarian cancer compared with that in normal
      ovaries (both P < 0.01), although it had no clinical significance in the
      progression-free survival. HB-EGF expression was significantly correlated with
      ADAM 17 expression (gamma = 0.437, P < 0.01). CONCLUSIONS: Our findings suggest
      that HB-EGF and ADAM 17 contribute to the progression of ovarian cancer and that
      HB-EGF plays a pivotal role in the aggressive behavior of a tumor in ovarian
      cancer.

PMID- 16000576
TI  - Immunologic purging of autologous peripheral blood stem cell products based on
      CD34 and CD133 expression can be effectively and safely applied in half of the
      acute myeloid leukemia patients.
AB  - PURPOSE: Several studies have shown survival benefit by autologous stem cell
      transplantation in acute myeloid leukemia (AML) after purging of grafts. This
      has, however, not been confirmed in randomized studies due to high toxicity of
      purging modalities for normal progenitor/stem cells. In this study, we
      investigated whether positive selection for CD34+ and/or CD133+ cells, which
      results in high recovery of normal progenitor/stem cells, is applicable for
      purging AML grafts. EXPERIMENTAL DESIGN: Positive selections of normal stem cells
      using CD34 and/or CD133 can be done if one or both markers are absent or have dim
      expression and remain so during the course of the disease. Marker expressions in
      newly diagnosed AML were measured with flow cytometry using a cutoff value for
      positivity of 1%. Stability of marker expression was studied by pairwise
      comparison of material at diagnosis and relapse. Leukemia associated phenotype
      expression was used to measure the efficacy of tumor cell reduction. RESULTS: In
      newly diagnosed AML (n = 165), we found no CD34 and/or CD133 expression in 32% of
      the cases and dim expression in 20% of the cases. No increase in the percentage
      of CD34+ cells (n = 44) and CD133+ cells (n = 29) was found in corresponding
      relapses. Positive selection using grafts contaminated with AML blasts, showing
      either no or dim expression of CD34 or CD133, resulted in a 3 to 4 log tumor cell
      reduction (n = 11) with median 50% recovery of normal stem cells. CONCLUSIONS:
      Purging by positive selection of CD34+ and/or CD133+ cells can safely,
      effectively, and reproducibly be applied in about 50% of AML cases.

PMID- 16000577
TI  - Association between polymorphisms in the DNA repair genes, XRCC1, APE1, and XPD
      and acute side effects of radiotherapy in breast cancer patients.
AB  - PURPOSE: Several DNA repair gene polymorphisms have been described, which affect
      DNA repair capacity and modulate cancer susceptibility. We evaluated the
      association of six polymorphisms in the DNA repair genes: XRCC1 (Arg194Trp,
      Arg280His, and Arg399Gln), APE1 (Asp148Glu), and XPD (Lys751Gln and Asp312Asn),
      with the risk of acute skin reactions following radiotherapy. DESIGN: We
      conducted a prospective study of 446 female patients with breast cancer who
      received radiotherapy after breast-conserving surgery. Individual genetic
      polymorphisms were determined using melting point analysis of sequence-specific
      hybridization probes. The development of acute skin reactions (moist
      desquamation) associated with DNA repair gene polymorphisms was modeled using Cox
      proportional hazards, accounting for cumulative biologically effective radiation
      dose. RESULTS: Overall, the development of acute toxicity, which presented in 77
      patients, was not associated with the genetic variants studied, although the
      hazard ratios (HR) were generally below 1. Risks were however differential by
      body mass index. Among normal-weight patients only, both carriers of the APE1
      148Glu and the XRCC1 399Gln alleles had decreased risk of acute skin reactions
      after radiotherapy (HR, 0.49 and 0.51, respectively). The results for XRCC1 were
      confirmed by haplotype analysis. When considering joint effects, we observed that
      compared with homozygote carriers of the wild-type allele in both genes, the risk
      was most strongly reduced in carriers of both APE1 148Glu and XRCC1 399Gln
      alleles with normal weight [HR, 0.19; 95% confidence interval (95% CI), 0.06
      0.56] but not in those with overweight (HR, 1.39; 95% CI, 0.56-3.45; Pinteraction
      = 0.009). CONCLUSION: The XRCC1 399Gln or APE1 148Glu alleles may be protective
      against the development of acute side effects after radiotherapy in patients with
      normal weight.

PMID- 16000578
TI  - A phase I trial of humanized monoclonal antibody A33 in patients with colorectal
      carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake.
AB  - PURPOSE: To determine the in vivo characteristics of huA33, a CDR-grafted
      humanized antibody against the A33 antigen, we have conducted an open-label, dose
      escalation, biopsy-based phase I trial of huA33 in patients with colorectal
      carcinoma. EXPERIMENTAL DESIGN: Patients with colorectal carcinoma were infused
      with [131I]huA33 (400 MBq: 10 mCi) and [125I]huA33 (40 MBq: 1 mCi) 1 week before
      surgery. There were four huA33 dose levels (0.25, 1.0, 5.0, and 10 mg/m2).
      Adverse events, pharmacokinetics, biodistribution, tumor biopsies, and immune
      responses to huA33 were evaluated. RESULTS: There were 12 patients entered into
      the trial (6 males and 6 females; age range, 39-66 years). No dose-limiting
      toxicity was observed. The biodistribution of huA33 showed excellent uptake of
      [131I]huA33 in metastatic colorectal carcinoma. Pharmacokinetic analysis showed
      no significant difference in terminal half-life (T1/2beta) between dose levels
      (mean +/- SD, 86.92 +/- 22.12 hours). Modeling of colon uptake of huA33 showed a
      T1/2 of elimination of 32.4 +/- 8.1 hours. Quantitative tumor uptake ranged from
      2.1 x 10(-3) to 11.1 x 10(-3) %ID/g, and tumor/normal tissue and tumor/serum
      ratios reached as high as 16.3:1 and 4.5:1, respectively. Biosensor analysis
      detected low-level human anti-human antibody responses in four patients following
      huA33 infusion. CONCLUSIONS: huA33 shows selective and rapid localization to
      colorectal carcinoma in vivo and penetrates to the center of large necrotic
      tumors, and colon elimination half-life of huA33 is equivalent to basal
      colonocyte turnover. The excellent targeting characteristics of this humanized
      antibody indicate potential for the targeted therapy of metastatic colorectal
      cancer in future trials.

PMID- 16000579
TI  - Phase I trial of 131I-huA33 in patients with advanced colorectal carcinoma.
AB  - PURPOSE: Humanized monoclonal antibody A33 (huA33) targets the A33 antigen which
      is expressed on 95% of colorectal cancers. A previous study has shown excellent
      tumor-targeting of iodine-131 labeled huA33 (131I-huA33). Therefore, we did a
      phase I dose escalation trial of 131I-huA33 radioimmunotherapy. EXPERIMENTAL
      DESIGNS: Fifteen patients with pretreated metastatic colorectal carcinoma each
      received two i.v. doses of 131I-huA33. The first was an outpatient trace-labeled
      "scout" dose for biodistribution assessment, followed by a second "therapy" dose.
      Three patients were treated at 20, 30, and 40 mCi/m2 dose levels, and six
      patients at 50 mCi/m2 to define the maximum tolerated dose. RESULTS: Hematologic
      toxicity was 131I dose-dependent, with one episode of grade 4 neutropenia and two
      episodes of grade 3 thrombocytopenia observed at 50 mCi/m2. The maximum tolerated
      dose was determined to be 40 mCi/m2. There were no acute infusion-related adverse
      events, and gastrointestinal toxicity was not observed despite uptake of 131I
      huA33 in bowel. Seven patients developed pruritus or rash, which was not related
      to 131I dose. There was excellent tumor-targeting of 131I-huA33 shown in all
      patients. The serum T1/2beta of 131I-huA33 was (mean +/- SD) 135.2 +/- 46.9
      hours. The mean absorbed tumor dose was 6.49 +/- 2.47 Gy/GBq. Four patients
      developed human anti-human antibodies. At restaging, 4 patients had stable
      disease, whereas 11 patients had progressive disease. CONCLUSION:
      Radioimmunotherapy using 131I-huA33 shows promise in targeting colorectal tumors,
      and is deliverable at a maximum tolerated dose of 40 mCi/m2. Further studies of
      131I-huA33 in combination with chemotherapy are planned.

PMID- 16000580
TI  - Systemic administration of an attenuated, tumor-targeting Salmonella typhimurium
      to dogs with spontaneous neoplasia: phase I evaluation.
AB  - PURPOSE: Genetically modified bacteria are a potentially powerful anticancer
      therapy due to their tumor targeting capacity, inherent antitumor activity, and
      ability to serve as efficient vectors for gene delivery. This study sought to
      characterize the acute and short-term toxicities and tumor colonization rates of
      a genetically modified Salmonella typhimurium (VNP20009) in dogs with spontaneous
      tumors, in the context of a phase I dose escalation trial. EXPERIMENTAL DESIGN:
      Forty-one pet dogs with a variety of malignant tumors received weekly or biweekly
      i.v. infusions of VNP20009, at doses ranging from 1.5 x 10(5) to 1 x 10(8)
      cfu/kg. Vital signs and clinicopathologic variables were monitored regularly.
      Incisional biopsies were obtained before and 1 week following the first infusion
      for histopathology and bacterial culture. RESULTS: The nominal maximum tolerated
      dose was 3 x 10(7) cfu/kg, with refractory fever and vomiting being the dose
      limiting toxicities. One treatment-related acute death occurred. Bacteria were
      cultured from tumor tissue in 42% of cases. Thirty-five patients were evaluable
      for antitumor response. Major antitumor responses were seen in 15% (4 complete
      response and 2 partial response), and disease stabilization for at least 6 weeks
      in 10%. CONCLUSIONS: Administration of VNP20009 at doses with acceptable toxicity
      results in detectable bacterial colonization of tumor tissue and significant
      antitumor activity in tumor-bearing dogs.

PMID- 16000581
TI  - Can molecular markers predict when to implement treatment with aromatase
      inhibitors in invasive breast cancer?
AB  - PURPOSE: Resistance to tamoxifen is linked to overexpression of HER2, and
      aromatase inhibitors show particular benefit in progesterone receptor (PR)
      negative patients. We previously reported reduced survival in patients
      overexpressing HER1, HER2, and HER3. We now show that both HER1-3 and PR status
      predicts for early relapse in estrogen receptor (ER)-positive tamoxifen-treated
      breast cancer patients. EXPERIMENTAL DESIGN: Tissue microarray technology was
      used to analyze 402 ER-positive tamoxifen-treated patients. Immunohistochemistry
      using epidermal growth factor receptor, HER2, HER3, HER4, and PR antibodies was
      done. Kaplan-Meier life table and Cox Regression analysis (log-rank testing of
      differences in breast cancer-related relapse on tamoxifen) was done. RESULTS:
      HER1-3 (but not HER4) overexpression predicted for early relapse on tamoxifen (P
      = 0.0060). PR-negative cases were also significantly more likely to relapse while
      on tamoxifen (P= 0.017). HER1-3-positive and/or PR-negative patients combined as
      a "high-risk" group were significantly more likely to relapse on tamoxifen in
      univariate (P < 0.0001) and Cox's multivariate analysis (P = 0.0069). However,
      this applied to early relapse on tamoxifen only, as any disease relapse after 3
      years of tamoxifen was unrelated to PR/HER status. CONCLUSIONS: We show that HER1
      3 and PR status can identify time-dependent de novo tamoxifen resistance with
      risk declining markedly after 3 years of tamoxifen treatment. These results
      parallel data from the ATAC and Intergroup Exemastane Study trials which suggest
      that whereas PR-negative patients derive greater benefit from initial aromatase
      inhibitor treatment, PR status has no effect on response when given as delayed
      treatment to those disease free on tamoxifen after 3 years.

PMID- 16000582
TI  - Association of Paclitaxel pharmacokinetics with the development of peripheral
      neuropathy in patients with advanced cancer.
AB  - PURPOSE: The shortening of infusion time from 3 to 1 hour decreases the systemic
      exposure (area under the curve, AUC) of total and unbound paclitaxel but
      increases the AUC of its vehicle Cremophor EL, whereas the time above total
      paclitaxel concentrations of 0.05 micromol/L (T >0.05) remains almost constant.
      As both Cremophor EL and paclitaxel are neurotoxic, we evaluated their
      pharmacodynamic effects on the development of peripheral neuropathy as the most
      important nonhematologic toxicity. EXPERIMENTAL DESIGN: Patients with advanced
      cancer of different origin were randomized to receive a maximum of 12 weekly
      given 1- or 3-hour infusions of 100 mg/m2 paclitaxel (Taxol). Twenty-four
      patients were assessable for both pharmacokinetics and peripheral neuropathy
      development evaluated by a clinical scoring system including sensory symptoms,
      strength, tendon reflexes, and vibratory sense. RESULTS: Patients with peripheral
      neuropathy development (n=14) received more weeks of therapy (P=0.056) and showed
      significantly higher T(>0.05) (P=0.022) and overall systemic drug exposures
      (weeks of therapy x AUC) for total paclitaxel (P=0.002) and unbound paclitaxel
      (P=0.003) than those without peripheral neuropathy. In Kaplan-Meier analyses,
      T(>0.05) > or = 10.6 hours (P=0.023), AUC of total paclitaxel > or = 4.7
      microg/mL x hour (P = 0.047), and AUC of unbound paclitaxel > or = 0.375
      microg/mL x hour (P = 0.095) were identified as being potential factors for
      peripheral neuropathy development. In a Cox regression analysis, only T(>0.05) >
      or = 10.6 hours remained as an independent risk factor (relative risk, 18.43; P =
      0.036) after adjusting for prior vincamycin (relative risk, 11.28; P = 0.038).
      CONCLUSIONS: From the results obtained in this study, it is concluded that
      exposure to paclitaxel but not Cremophor EL is associated with peripheral
      neuropathy development.

PMID- 16000583
TI  - Combination therapy of insulin-like growth factor binding protein-3 and retinoid
      X receptor ligands synergize on prostate cancer cell apoptosis in vitro and in
      vivo.
AB  - We have previously identified the retinoid X receptor-alpha (RXRalpha) as an
      insulin-like growth factor binding protein-3 (IGFBP-3) nuclear binding partner,
      which is required for IGFBP-3-induced apoptosis. In the current study, we
      investigated the biological interactions of the RXR ligand, VTP194204 and rhIGFBP
      3, in vitro and in vivo. In vitro, IGFBP-3 and VTP194204 individually induced
      apoptosis, and suppressed cell growth in prostate cancer cell lines in an
      additive manner. In vivo, LAPC-4 xenograft-bearing severe combined
      immunodeficiency mice treated daily with saline, IGFBP-3, and/or VTP194204 for 3
      weeks showed no effect of individual treatments with IGFBP-3 or VTP194204 on
      tumor growth. However, the combination of IGFBP-3 and VTP194204 treatments
      inhibited tumor growth by 50% and induced a significant reduction in serum
      prostate-specific antigen levels. In terminal nucleotidyl transferase-mediated
      nick end labeling immunohistochemistry of LAPC-4 xenografts, there was modest
      induction of apoptosis with either IGFBP-3 or VTP194204 individual treatment, but
      combination therapy resulted in massive cell death, indicating that IGFBP-3 and
      VTP194204 have a synergistic effect in preventing tumor growth by apoptosis
      induction. In summary, this is an initial description of the successful
      therapeutic use of IGFBP-3 as a cancer therapy in vivo, and shows that
      combination treatment of IGFBP-3 and RXR ligand has a synergistic effect on
      apoptosis induction leading to substantial inhibition of prostate cancer
      xenograft growth. Taken together, these observations suggest that combination
      therapy with IGFBP-3 and RXR ligands may have therapeutic potential for prostate
      cancer treatment.

PMID- 16000584
TI  - Induction of apoptosis using inhibitors of lysophosphatidic acid acyltransferase
      beta and anti-CD20 monoclonal antibodies for treatment of human non-Hodgkin's
      lymphomas.
AB  - PURPOSE: Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is a
      transmembrane enzyme critical for the biosynthesis of phosphoglycerides whose
      product, phosphatidic acid, plays a key role in raf and AKT/mTor-mediated signal
      transduction. EXPERIMENTAL DESIGN: LPAAT-beta may be a novel target for
      anticancer therapy, and, thus, we examined the effects of a series of inhibitors
      of LPAAT-beta on multiple human non-Hodgkin's lymphoma cell lines in vitro and in
      vivo. RESULTS: We showed that five LPAAT-beta inhibitors at doses of 500 nmol/L
      routinely inhibited growth in a panel of human lymphoma cell lines in vitro by
      >90%, as measured by [3H]thymidine incorporation. Apoptotic effects of the LPAAT
      beta inhibitors were evaluated either alone or in combination with the anti-CD20
      antibody, Rituximab. The LPAAT-beta inhibitors induced caspase-mediated apoptosis
      at 50 to 100 nmol/L in up to 90% of non-Hodgkin's lymphoma cells. The combination
      of Rituximab and an LPAAT-beta inhibitor resulted in a 2-fold increase in
      apoptosis compared with either agent alone. To assess the combination of
      Rituximab and a LPAAT-beta inhibitor in vivo, groups of athymic mice bearing s.c.
      human Ramos lymphoma xenografts were treated with the LPAAT-beta inhibitor CT
      32228 i.p. (75 mg/kg) daily for 5 d/wk x 4 weeks (total 20 doses), Rituximab i.p.
      (10 mg/kg) weekly x 4 weeks (4 doses total), or CT-32228 plus Rituximab combined.
      Treatment with either CT-32228 or Rituximab alone showed an approximate 50%
      xenograft growth delay; however, complete responses were only observed when the
      two agents were delivered together. CONCLUSIONS: These data suggest that
      Rituximab, combined with a LPAAT-beta inhibitor, may provide enhanced therapeutic
      effects through apoptotic mechanisms.

PMID- 16000585
TI  - Relationship between plasma exposure of 9-nitrocamptothecin and its 9
      aminocamptothecin metabolite and antitumor response in mice bearing human colon
      carcinoma xenografts.
AB  - 9-Nitrocamptothecin has completed phase III studies in patients with newly
      diagnosed and refractory pancreatic cancer; however, the optimal 9
      nitrocamptothecin treatment regimen is unclear. We used an intermittent schedule
      of 9-nitrocamptothecin to evaluate the relationship between plasma exposure of 9
      nitrocamptothecin and its 9-aminocamptothecin metabolite and antitumor response
      in mice bearing human colon carcinoma xenografts. 9-Nitrocamptothecin was given
      orally at 0.44, 0.67, or 1.0 mg/kg/d qd x 5d x 2 weeks repeated q 4 weeks for two
      cycles to female C.B-17 SCID mice bearing HT29 or ELC2 human colon xenografts.
      Pharmacokinetic studies were done after oral administration of 0.67 mg/kg x 1.
      Serial samples were obtained and 9-nitrocamptothecin and 9-aminocamptothecin
      lactone concentrations in plasma were determined by high-performance liquid
      chromatography analysis with fluorescence detection. The areas under plasma
      concentration versus time curve (AUC) from 0 to infinity for 9-nitrocamptothecin
      and 9-aminocamptothecin were calculated. The antitumor activity of 9
      nitrocamptothecin was dose-dependent in both colon xenografts. At all doses, 9
      nitrocamptothecin treatment resulted in significant antitumor activity in both
      xenografts compared with vehicle-treated and control groups and achieved levels
      of tumor regression that met criteria (minimum %T/C < or = 40%) for antitumor
      activity. In mice bearing HT29 xenografts, the 9-nitrocamptothecin and 9
      aminocamptothecin lactone AUCs after administration of 9-nitrocamptothecin at
      0.67 mg/kg were 41.3 and 5.7 ng/mL h, respectively. The responses seen in these
      xenograft models occurred at systemic exposures that are tolerable in adult
      patients. These results suggest that the intermittent schedule of 9
      nitrocamptothecin may be an active regimen in patients with colorectal carcinoma.

PMID- 16000586
TI  - In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the
      trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine,
      bohemine and CYC202.
AB  - PURPOSE: To investigate pharmacokinetic-pharmacodynamic relationships for the
      trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine,
      bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon
      carcinoma model. EXPERIMENTAL DESIGN: The in vitro activity of the agents was
      determined in a human tumor panel using the sulforhodamine B assay. The
      concentration and time dependence was established in HCT116 cells. Molecular
      biomarkers, including RB phosphorylation and cyclin expression, were assessed by
      Western blotting. Pharmacokinetic properties were characterized in mice following
      analysis by liquid chromatography-tandem mass spectrometry. Based on these
      studies, a dosing regimen was developed for CYC202 that allowed therapeutic
      exposures in the HCT116 tumor xenograft. RESULTS: The antitumor potency of the
      agents in vitro was in the order olomoucine (IC50, 56 micromol/L) < bohemine
      (IC50, 27 micromol/L) < CYC202 (IC50, 15 micromol/L), corresponding to their
      activities as cyclin-dependent kinase inhibitors. Antitumor activity increased
      with exposure time up to 16 hours. The agents caused inhibition of RB and RNA
      polymerase II phosphorylation and depletion of cyclins. They exhibited relatively
      rapid clearance following administration to mice. CYC202 displayed the slowest
      clearance from plasma and the highest tumor uptake, with oral bioavailability of
      86%. Oral dosing of CYC202 gave active concentrations in the tumor, modulation of
      pharmacodynamic markers, and inhibition of tumor growth. CONCLUSIONS: CYC202
      showed therapeutic activity on human cancer cell lines in vitro and on
      xenografts. Pharmacodynamic markers are altered in vitro and in vivo, consistent
      with the inhibition of cyclin-dependent kinases. Such markers may be potentially
      useful in the clinical development of CYC202 and other cyclin-dependent kinase
      inhibitors.

PMID- 16000587
TI  - Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory
      and invasive carcinoma.
AB  - PURPOSE: Although a variety of malignant tumors are susceptible to therapy with
      oncolytic herpes simplex viruses, the determinants of tumor sensitivity to these
      viruses are poorly understood. Nectin-1 is a cell surface adhesion molecule that
      is a component of intercellular adherens junctions and also functions as a herpes
      viral receptor. Because highly invasive cells may have decreased intercellular
      adhesion, we sought to determine if such cells might also have altered
      availability of cell surface nectin-1 to act as a herpes receptor. EXPERIMENTAL
      DESIGN AND RESULTS: A series of squamous cell carcinoma lines of increasing
      migratory and invasive potential, termed MG1-MG14, were selected by serial
      passages of murine SCC7 through Matrigel invasion chambers. Available cell
      surface nectin-1 was enhanced on the MG11 and MG14 cell lines in comparison to
      SCC7 as measured by cellular ELISA and immunofluorescence microscopy. A
      replication-competent, oncolytic herpes virus (NV1023) showed an increased
      ability to enter MG11 and MG14 cells as compared with SCC7 cells. Furthermore,
      MG11 and MG14 supported increased herpes viral replication and cytotoxicity over
      SCC7. For all three of the cell lines, viral entry assays revealed that the
      actively migrating cells were significantly more susceptible to herpes infection
      than the nonmigrating cells. CONCLUSIONS: These results show that malignant cells
      with highly migratory and invasive properties may exhibit increased cell surface
      nectin-1 availability, which may serve as a herpes viral receptor to enhance the
      efficacy of herpes oncolytic therapy. This finding has implications regarding
      patient selection for future clinical trials using these promising therapeutic
      vectors.

PMID- 16000588
TI  - Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal
      squamous cell carcinoma.
AB  - PURPOSE: In the present study, we investigated the degree of protein expression
      and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell
      lines and freshly isolated tumors, and trastuzumab-mediated biological activity,
      in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2
      expressing esophageal SCC cell lines. EXPERIMENTAL DESIGN: Ten different SCC cell
      lines with various levels of HER-2 status evaluated by flow cytometry,
      immunocytochemistry (HercepTest), and fluorescence in situ hybridization were
      evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated
      by trastuzumab. RESULTS: Trastuzumab induced ADCC against HER-2-expressing
      esophageal SCC and the activities reflected the degree of HER-2 expression
      analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in
      situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against
      transforming growth factor-beta-producing SCC was enhanced by the treatment with
      SB-431542, which is a selective inhibitor of the phosphorylation induced by
      transforming growth factor-beta. There were very marginal effects of anti
      proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2
      expressing esophageal SCC. CONCLUSION: HER-2-expressing esophageal SCC cells
      could be killed by trastuzumab-mediated ADCC and the activity reflected the
      degree of HER-2 expression detected by flow cytometry.

PMID- 16000589
TI  - Timing is everything: preclinical evidence supporting simultaneous rather than
      sequential chemohormonal therapy for prostate cancer.
AB  - PURPOSE: Androgen ablation is the mainstay of systemic therapy for prostate
      cancer, with cytotoxic therapies reserved for hormone-refractory disease. It is
      not clear, however, that this is the most appropriate sequence of interventions
      for this disease. This study addresses the ideal timing of systemic treatments in
      the Shionogi and LNCaP xenograft models. We explored the hypothesis that stress
      induced gene expression changes after chemotherapy can induce a hormone
      independent phenotype. EXPERIMENTAL DESIGN: Three groups of mice bearing either
      Shionogi or LNCaP xenografts were treated with (a) initial castration and delayed
      paclitaxel, (b) initial paclitaxel and delayed castration, or (c) simultaneous
      castration plus paclitaxel. End points were time to tumor progression and time to
      sacrifice. Microarray and reverse transcription-PCR analyses were carried out to
      assess changes in gene expression induced by paclitaxel. RESULTS: Mice receiving
      simultaneous therapy showed a significant improvement in median time to
      progression (TTP: Shionogi, 65 versus 38 days, P = 0.004; LNCaP, 105 versus 70
      days, P = 0.032) and time to sacrifice (Shionogi, 83 versus 66 days, P < 0.014)
      versus best sequential therapy. A marked lack of response to castration was
      observed after initial paclitaxel therapy. Gene expression and reverse
      transcription-PCR studies confirmed that several genes known to play a role in
      androgen independence were up-regulated in response to paclitaxel exposure.
      CONCLUSIONS: In laboratory models of prostate cancer, simultaneous androgen
      deprivation plus paclitaxel is more effective than sequential treatments. These
      findings provide preclinical proof-of-principle for ongoing clinical trials
      addressing the role and timing of systemic therapies in prostate cancer.

PMID- 16000590
TI  - Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing
      DNA repair activity.
AB  - PURPOSE: Histone deacetylase (HDAC) inhibitors have emerged recently as promising
      anticancer agents. They arrest cells in the cell cycle and induce differentiation
      and cell death. The antitumor activity of HDAC inhibitors has been linked to
      their ability to induce gene expression through acetylation of histone and
      nonhistone proteins. However, it has recently been suggested that HDAC inhibitors
      may also enhance the activity of other cancer therapeutics, including
      radiotherapy. The purpose of this study was to evaluate the ability of HDAC
      inhibitors to radiosensitize human melanoma cells in vitro. EXPERIMENTAL DESIGN:
      A panel of HDAC inhibitors that included sodium butyrate (NaB), phenylbutyrate,
      tributyrin, and trichostatin A were tested for their ability to radiosensitize
      two human melanoma cell lines (A375 and MeWo) using clonogenic cell survival
      assays. Apoptosis and DNA repair were measured by standard assays. RESULTS: NaB
      induced hyperacetylation of histone H4 in the two melanoma cell lines and the
      normal human fibroblasts. NaB radiosensitized both the A375 and MeWo melanoma
      cell lines, substantially reducing the surviving fraction at 2 Gy (SF2), whereas
      it had no effect on the normal human fibroblasts. The other HDAC inhibitors,
      phenylbutyrate, tributyrin, and trichostatin A had significant radiosensitizing
      effects on both melanoma cell lines tested. NaB modestly enhanced radiation
      induced apoptosis that did not correlate with survival but did correlate with
      functional impairment of DNA repair as determined based on the host cell
      reactivation assay. Moreover, NaB significantly reduced the expression of the
      repair-related genes Ku70 and Ku86 and DNA-dependent protein kinase catalytic
      subunit in melanoma cells at the protein and mRNA levels. Normal human
      fibroblasts showed no change in DNA repair capacity or levels of DNA repair
      proteins following NaB treatment. We also examined gamma-H2AX phosphorylation as
      a marker of radiation response to NaB and observed that compared with controls,
      gamma-H2AX foci persisted long after ionizing exposure in the NaB-treated cells.
      CONCLUSIONS: HDAC inhibitors radiosensitize human tumor cells by affecting their
      ability to repair the DNA damage induced by ionizing radiation and that gamma
      H2AX phosphorylation can be used as a predictive marker of radioresponse.

PMID- 16000591
TI  - Antivascular therapy for orthotopic human ovarian carcinoma through blockade of
      the vascular endothelial growth factor and epidermal growth factor receptors.
AB  - PURPOSE: We determined whether the administration of the tyrosine kinase
      inhibitor, AEE788, which targets the epidermal growth factor receptor and the
      vascular endothelial growth factor receptor, alone or in combination with
      paclitaxel, can inhibit progressive growth of human ovarian carcinoma in the
      peritoneal cavity of female nude mice. EXPERIMENTAL DESIGN: Western blot analysis
      and immunohistochemical analysis identified the optimal dose and schedule of
      AEE788 therapy. In several different experiments, paclitaxel-sensitive and
      paclitaxel-resistant human ovarian carcinoma cells were injected into the
      peritoneal cavity of nude mice. Seven days later, treatment with saline
      (control), AEE788 alone, paclitaxel alone, or a combination of AEE788 and
      paclitaxel began and continued for 45 days when the mice were necropsied. In
      independent survival experiments, the mice were necropsied when they became
      moribund. RESULTS: Oral administration of AEE788 inhibited phosphorylation of the
      epidermal growth factor receptor and vascular endothelial growth factor receptor
      for up to 48 hours. Treatment with AEE788 plus paclitaxel significantly reduced
      tumor weight and increased survival of mice implanted with paclitaxel-sensitive
      cell lines compared with control mice or mice treated with AEE788 alone or
      paclitaxel alone. In mice implanted with paclitaxel-resistant cells, the
      combination therapy also significantly reduced tumor weight but did not prolong
      survival. The combination therapy induced apoptosis of both tumor cells and tumor
      associated endothelial cells. CONCLUSIONS: The administration of AEE788 and
      paclitaxel inhibits the progression of human ovarian carcinoma in the peritoneal
      cavity of female nude mice, in part, by inducing apoptosis of tumor-associated
      endothelial cells.

PMID- 16000592
TI  - Inhibition of glioblastoma angiogenesis and invasion by combined treatments
      directed against vascular endothelial growth factor receptor-2, epidermal growth
      factor receptor, and vascular endothelial-cadherin.
AB  - PURPOSE: Inhibition of angiogenesis can influence tumor cell invasion and
      metastasis. We previously showed that blockade of vascular endothelial growth
      factor receptor-2 (VEGFR-2) with the monoclonal antibody DC101 inhibited
      intracerebral glioblastoma growth but caused increased tumor cell invasion along
      the preexistent vasculature. In the present study, we attempted to inhibit glioma
      cell invasion using a monoclonal antibody against the epidermal growth factor
      receptor (EGFR), which in the context of human glioblastomas, has been implicated
      in tumor cell invasion. In addition, we analyzed whether blockade of vascular
      endothelial (VE)-cadherin as a different antiangiogenic target could also inhibit
      glioblastoma angiogenesis and growth. EXPERIMENTAL DESIGNS: Nude mice who
      received intracerebral glioblastoma xenografts were treated using monoclonal
      antibodies against VEGFR-2 (DC101), EGFR (C225), and VE-cadherin (E4G10) either
      alone or in different combinations. RESULTS: Increased tumor cell invasion
      provoked by DC101 monotherapy was inhibited by 50% to 66% by combined treatment
      with C225 and DC101. C225 inhibited glioblastoma cell migration in vitro, but had
      no effect on the volume of the main tumor mass or on tumor cell proliferation or
      apoptosis in vivo, either alone or in combination with DC101. The anti-VE
      cadherin monoclonal antibody E4G10 was a weaker inhibitor of tumor angiogenesis
      and growth than DC101, and also caused a weaker increase in tumor cell invasion.
      CONCLUSIONS: Inhibition of angiogenesis achieved by blocking either VEGFR-2 or VE
      cadherin can cause increased glioma cell invasion in an orthotopic model.
      Increased tumor cell invasion induced by potent inhibition of angiogenesis with
      DC101 could be inhibited by simultaneous blockade of EGFR.

PMID- 16000593
TI  - AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity
      against imatinib-resistant chronic myeloid leukemia.
AB  - Resistance to or intolerance of imatinib in patients with Philadelphia chromosome
      positive chronic myelogenous leukemia (CML) has encouraged the development of
      more potent Bcr-Abl inhibitors. AMN107 is a novel, orally bioavailable ATP
      competitive inhibitor of Bcr-Abl. The effects of AMN107 were compared with those
      of imatinib on imatinib-sensitive (KBM5 and KBM7) and imatinib-resistant CML cell
      lines (KBM5-STI571R1.0 and KBM7-STI571R1.0). Compared with the antiproliferative
      activity of imatinib, AMN107 was 43 times more potent in KBM5 (IC50 of 11.3
      versus 480.5 nmol/L) and 60 times more potent in KBM7 (IC50 of 4.3 versus 259.0
      nmol/L) cells. IC50 for AMN107 and imatinib were 2,418.3 and 6,361.4 nmol/L,
      respectively, in KBM5-STI571R1.0, and 97.2 and 2,497.3 nmol/L, respectively, in
      KBM7-STI571R1.0 cells. AMN107 inhibited autophosphorylation of Bcr-Abl kinase
      more effectively than imatinib in all cell lines. They had similar effects on
      cell cycle progression and apoptotic response in these cell lines. Among severe
      combined immunodeficient mice bearing KBM5 cells, mean survival times of groups
      treated with 10, 20, and 30 mg/kg/d of AMN107, starting day 20 after leukemic
      cell grafting and continuing for 20 days, were 144%, 159%, and 182%,
      respectively, compared with controls. These results strongly support
      investigation of the clinical efficacy of AMN107 in patients with CML.

PMID- 16000594
TI  - Multigene targeting with antisense oligodeoxynucleotides: an exploratory study
      using primary human leukemia cells.
AB  - PURPOSE: We previously reported that the c-myb and Vav proto-oncogenes are
      amenable to silencing with antisense oligodeoxynucleotides and that inhibition of
      either impairs leukemic cell growth. Because the expression of these genes is not
      known to be linked, we sought to determine the therapeutic value of silencing
      both genes simultaneously in K562 and primary patient (n = 9) chronic myelogenous
      leukemia cells. EXPERIMENTAL DESIGN: K562 and primary chronic myelogenous
      leukemia cells were exposed to antisense oligodeoxynucleotides (alone or in
      combination) for 24 or 72 hours and then cloned in methylcellulose cultures.
      Effects on K562 cluster, and blast-forming unit-erythroid colonies and
      granulocyte-macrophage colony-forming units were determined and correlated with
      the ability to down-regulate the targeted mRNA. RESULTS: After 24-hour exposure,
      K562 cell growth was inhibited in a sequence specific, dose-responsive manner
      with either c-myb or Vav antisense oligodeoxynucleotides. Exposure to both
      oligodeoxynucleotides simultaneously considerably enhanced growth inhibition and
      accelerated apoptosis. Primary cell results were more complex. After 24- and 72
      hour exposures to either anti-vav or anti-myb antisense oligodeoxynucleotides,
      equivalent colony-forming unit inhibition was observed. Exposing cells to both
      antisense oligodeoxynucleotides simultaneously for 24 hours did not result in
      additional inhibition of colony formation. However, after 72-hour incubation with
      both oligodeoxynucleotides, colony formation was diminished significantly when
      compared with either oligodeoxynucleotides alone (from approximately 30% to
      approximately 78% for granulocyte-macrophage colony-forming unit; approximately
      50% to approximately 80% for blast-forming unit-erythroid). CONCLUSIONS: We
      hypothesize that exposing primary leukemic cells to antisense
      oligodeoxynucleotides targeted to two, or possibly more, genes might
      significantly augment the therapeutic utility of these molecules.

PMID- 16000596
TI  - Dietary supplementation with silymarin inhibits 3,2'-dimethyl-4-aminobiphenyl
      induced prostate carcinogenesis in male F344 rats.
AB  - PURPOSE: Silymarin has been shown to be a potent anticarcinogenic agent. Here, we
      investigated the modifying effects of dietary feeding with a naturally occurring
      polyphenolic antioxidant flavonoid silymarin on 3,2'-dimethyl-4-aminobiphenyl
      (DMAB)-induced prostatic carcinogenesis in male F344 rats. EXPERIMENTAL DESIGN:
      Male F344 rats were given s.c. injections of DMAB (25 mg/kg body weight) every
      other week for 20 weeks. They also received the experimental diet containing 100
      or 500 ppm silymarin for 40 weeks, starting 1 week after the last dosing of DMAB.
      All of the rats were sacrificed 60 weeks after the start of the experiment.
      Histopathology and immunohistochemistry for proliferative cell nuclear antigen,
      cyclin D1, and apoptotic indices were done in the prostatic lesions, including
      invasive adenocarcinomas, intraepithelial neoplasms, and nonlesional glands.
      RESULTS: Dietary feeding with 500 ppm silymarin significantly inhibited the
      incidence of prostatic adenocarcinoma when compared with the DMAB-alone group
      (17.6% versus 50.0%, P < 0.05). The proliferative cell nuclear antigen- and
      cyclin D1-positive indices in adenocarcinomas, prostatic intraepithelial
      neoplasm, and nonlesional glands in rats treated with DMAB and silymarin were
      slightly lower than that of the DMAB-alone group. Also, dietary administration of
      silymarin increased apoptotic index in prostatic adenocarcinoma by measuring
      immunohistochemically positive nuclei for ssDNA. CONCLUSIONS: Our results
      indicate that silymarin exerts chemopreventive ability against chemically induced
      prostatic carcinogenesis through apoptosis induction and modification of cell
      proliferation.

PMID- 16000595
TI  - Combined dendritic cell cryotherapy of tumor induces systemic antimetastatic
      immunity.
AB  - PURPOSE: Cryotherapy of localized prostate, renal, and hepatic primary tumors and
      metastases is considered a minimally invasive treatment demonstrating a low
      complication rate in comparison with conventional surgery. The main drawback of
      cryotherapy is that it has no systemic effect on distant metastases. We
      investigated whether intratumoral injections of dendritic cells following
      cryotherapy of local tumors (cryoimmunotherapy) provides an improved approach to
      cancer treatment, combining local tumor destruction and systemic anticancer
      immunity. EXPERIMENTAL DESIGNS: The 3LL murine Lewis lung carcinoma clone D122
      and the ovalbumin-transfected B16 melanoma clone MO5 served as models for
      spontaneous metastasis. The antimetastatic effect of cryoimmunotherapy was
      assessed in the lung carcinoma model by monitoring mouse survival, lung weight,
      and induction of tumor-specific CTLs. The mechanism of cryoimmunotherapy was
      elucidated in the melanoma model using adoptive transfer of T cell receptor
      transgenic OT-I CTLs into the tumor-bearing mice, and analysis of Th1/Th2
      responses by intracellular cytokine staining in CD4 and CD8 cells. RESULTS:
      Cryoimmunotherapy caused robust and tumor-specific CTL responses, increased Th1
      responses, significantly prolonged survival and dramatically reduced lung
      metastasis. Although intratumor administration of dendritic cells alone increased
      the proliferation rate of CD8 cells, only cryoimmunotherapy resulted in the
      generation of effector memory cells. Furthermore, cryoimmunotherapyprotected mice
      that had survived primary MO5 tumors from rechallenge with parental tumors.
      CONCLUSIONS: These results present cryoimmunotherapy as a novel approach for
      systemic treatment of cancer. We envisage that cryotherapy of tumors combined
      with subsequent in situ immunotherapy by autologous unmodified immature dendritic
      cells can be applied in practice.

PMID- 16000597
TI  - Methylation and messenger RNA expression of p15INK4b but not p16INK4a are
      independent risk factors for ovarian cancer.
AB  - PURPOSE: The purpose of this research was to compare methylation status and mRNA
      expression of p15INK4b and p16INK4a in serous epithelial ovarian cancer tissues
      and normal ovarian tissues. EXPERIMENTAL DESIGN: We analyzed the DNA methylation
      status and mRNA expression of p15INK4b and p16INK4a in 52 ovarian cancer
      specimens and 40 normal ovarian specimens by using methylation-specific PCR and
      real-time reverse transcription-PCR, respectively. RESULTS: Although the p15INK4b
      and p16INK4a mRNA expression levels were highly correlated with each other (P <
      0.001), the methylation status did not seem to be linked with levels of mRNA
      expression, as no association between the two events was found for either gene.
      Promoter hypermethylation of p15(INK4b) was more common in ovarian cancer (30.8%
      for the 52 cases) than in normal ovaries (5% for the 40 controls without ovarian
      cancer; P = 0.005) but not methylation of p16INK4a (25% for cancer versus 37.5%
      for normal; P = 0.288). The relative mRNA expression levels of p15INK4b were
      significantly lower in ovarian cancer (12.9%) than in normal ovaries (41.7%; P =
      0.008) but not those of p16INK4a (27% for cases versus 32.8% for controls; P =
      0.754). Only high methylation rate and low mRNA expression of p15INK4b were
      independent risk factors for ovarian cancer (adjusted odds ratio, 5.67; 95%
      confidence interval, 0.85-37.9 for high methylation rate and odds ratio, 8.98;
      95% confidence interval, 1.58-50.9 for low mRNA expression, respectively).
      CONCLUSIONS: Our results suggest that epigenetic alterations in p15INK4b but not
      p16INK4a have an important role in ovarian carcinogenesis and that mechanisms
      other than methylation may exist to reduce gene expression of p15INK4b in ovarian
      cancer.

PMID- 16000598
TI  - Imatinib is not a potential alternative treatment for uterine leiomyosarcoma.

PMID- 16000599
TI  - Early stage lung cancer--new approaches to evaluation and treatment: conference
      summary statement.

PMID- 16000600
TI  - Computed tomography screening for lung cancer: principles and results.
AB  - In modern healthcare, one of the most public, most important, and at the same
      time complicated and scientifically demanding topics is screening for a cancer.
      Mammographic screening for breast cancer has been, in the last few years, a
      particularly hotly disputed topic in scientific and public policy circles, with
      similar confusion and frustration widely reported and thus disseminated by the
      mass media. Most remarkably, this debacle has taken place against the backdrop
      of, and despite,a truly enormous amount of completed research designed to address
      the usefulness of such screening. To avoid a "mammography" debacle for lung
      cancer, the fundamental principles of screening need to be presented as we have
      come to think of them. Although it is generally accepted that low-dose computed
      tomography (CT) screening leads to early diagnosis of lung cancer in a high
      percentage of the cases, the logical consequence of the current knowledge is that
      annual CT screening prevents death from lung cancer. Thus, it is not whether CT
      screening is effective, rather the magnitude of its benefit which needs to be
      determined. We will illustrate our approach by discussing the Early Lung Cancer
      Action Project and its New York and International sequels.

PMID- 16000601
TI  - Limitations of screening for lung cancer with low-dose spiral computed
      tomography.
AB  - Past lung cancer screening trials in the United States with chest X-ray and
      sputum cytology were not able to show any decrease in lung cancer mortality;
      however, these trials are over 20 years old. Recent follow-up of the Mayo Lung
      Project showed a better survival from lung cancer in the screened arm, but no
      difference in overall mortality, suggesting an overdiagnosis of nonfatal cancers.
      Recent reports of low radiation dose spiral computed tomography (CT) chest
      screening for lung cancer have shown that CT screening detects cancers at a
      smaller size than chest X-rays. To date, there have been no randomized trials of
      CT versus observation or chest radiographs for screening purposes. All data
      available thus far on CT screening are from phase II proof-of-principle trials.
      The major limitations of CT screening, discussed here, include (a) a high rate of
      nodule detection: over 50% of participants will have at least one noncalcified
      nodule; (b) resulting follow-up CT scans, associated with increased costs; (c)
      cost and morbidity of biopsy or resection of benign noncalcified nodule (20-25%
      of such procedures in several trials); and (d) a small, but difficult to
      quantify, risk of cancer associated with multiple follow-up CT scans.

PMID- 16000602
TI  - Clinical issues in the management of early lung cancer.
AB  - Lung cancer is commonly diagnosed after metastatic spread, when therapies are
      rarely curative, providing an impetus for continued research directed at
      exploring approaches for cost-effective early lung cancer detection. Recently
      published pilot studies across three continents support a benefit of spiral
      computed tomography (CT) in detecting earlier stage non-small cell lung cancer.
      Improved resolution of early lung cancer is a result of significant changes in CT
      imaging hardware and software. The status and implications of these developments
      are reviewed. Many aspects of the management of screening for early lung cancer
      could be informed by optimizing the downstream clinical management of potential
      lung cancers identified by CT screening. The first and most critical issue is
      whether or not this improved detection rate is clearly associated with a
      reduction in lung cancer-related mortality. However, other related issues such as
      cost-benefit evaluations are also considered. If smaller, truly localized primary
      cancer can be routinely detected, then options for less morbid interventions
      would also be desirable. The rapid improvement in resolution and cost of spiral
      CT has provided a powerful impetus to reconsider the possibilities for achieving
      safe, economical, and meaningful early lung cancer detection.

PMID- 16000603
TI  - Future of early detection of lung cancer: the role of mouse models.
AB  - Early detection represents one of the most promising approaches to improving lung
      cancer survival. To date, no screening strategies have been shown to decrease
      mortality from the disease. Furthermore, no reliable circulating biomarkers of
      lung cancer have been identified that allow early diagnosis. With the advent of
      gene targeting technology, new genetically engineered mouse models of lung cancer
      closely recapitulate the pathobiology of human disease. These mouse models have
      enabled novel approaches to early detection, including the identification of
      cancer-associated serum markers using proteomic technologies and the development
      of new molecular imaging tools. The application of innovative technologies to
      accurate mouse models promises to accelerate the discovery of new molecular
      targets and imaging biomarkers for the early detection of lung cancer.

PMID- 16000604
TI  - Localized non-small cell lung cancer: adjuvant radiotherapy in the era of
      effective systemic therapy.
AB  - Investigators in Europe, Canada, and the United States recently established a
      definitive role for adjuvant systemic chemotherapy following resection of early
      stage non-small cell lung cancer (NSCLC). This was no small accomplishment, as
      upward of 20 randomized trials had previously been conducted. The role of
      postoperative radiotherapy (PORT) has been studied with far less vigor in the
      modern era. A 1998 meta-analysis of randomized trials suggesting that PORT was
      detrimental to survival included studies of doubtful quality. The value of PORT
      should be considered in the same context as recent chemotherapy trials. Advances
      in imaging have improved the accuracy of staging, patient selection, and target
      definition. Modern dosimetry and accelerator technologies have advanced the
      capacity to deliver radiation to the target with less tissue toxicity. Evolving
      philosophies in dosing and fractionation should improve the therapeutic ratio.
      Finally, it is reasonable to assume that the importance of local control will be
      enhanced in the setting of better systemic therapies. We will review the data on
      PORT and address critical issues in the design of trials to assess the role of
      modern radiotherapy in the integrated approach to management of early-stage
      NSCLC.

PMID- 16000605
TI  - The ALPI Trial: the Italian/European experience with adjuvant chemotherapy in
      resectable non-small lung cancer.
AB  - Postoperative treatments for lung cancer have been evaluated for more than two
      decades, but in the majority of the studies no significant and clinically
      meaningful effect on survival has been shown. In 1995, a meta-analysis of eight
      cisplatin-based adjuvant chemotherapy trials in 1,394 patients with non-small
      cell lung cancer showed a 13% reduction in the risk of death (P = 0.08). The
      nonstatistically significant benefit reported in the meta-analysis prompted the
      planning of several randomized studies of platinum-based chemotherapy. Three
      studies addressed the issue of adjuvant chemotherapy in all the resected stages
      of non-small cell lung cancer (I-IIIA): the Italian/European study Adjuvant Lung
      Cancer Project Italy, the International Adjuvant Lung Cancer study, and the
      British Big Lung Trial. In contrast to the International Adjuvant Lung Cancer,
      the Adjuvant Lung Cancer Project Italy and the underpowered British Big Lung
      Trial failed to prospectively confirm a significant role of adjuvant chemotherapy
      in completely resected non-small cell lung cancer. In this article, we will
      discuss the findings of the Adjuvant Lung Cancer Project Italy study in the
      context of the International Adjuvant Lung Cancer and British Big Lung Trial.

PMID- 16000606
TI  - Adjuvant chemotherapy for non-small cell lung cancer: contribution of the
      International Adjuvant Lung Trial.
AB  - The recently reported International Adjuvant Lung Cancer Trial (IALT) was
      designed to assess the potential benefit of three to four cycles of adjuvant
      cisplatin-based chemotherapy after complete resection of non-small cell lung
      cancer (NSCLC). Each center predetermined the cisplatin dose (total 300-400
      mg/m(2)), the combined drug (etoposide or a Vinca alkaloid), and the radiotherapy
      policy. From 1995 to 2000, 1,867 patients were randomized in 148 centers from 33
      countries. On September 1, 2002, median follow-up was 56 months and >98% of
      patients had an updated follow-up. Overall survival was significantly different
      between the two arms: 5-year survival rate was 44.5% in the chemotherapy arm
      versus 40.4% in the control arm [relative risk = 0.86 (0.76-0.98), P < 0.03].
      Disease-free survival, incidence of local recurrence, and incidence of distant
      metastases (but not brain metastases) were likewise significantly different, with
      an advantage for the chemotherapy arm. We concluded that adjuvant cisplatin-based
      chemotherapy in resected NSCLC should become part of the standard management of
      operable NSCLC. Two other recently reported randomized prospective studies also
      showed a significant benefit for postoperative platin-based doublets in stage IB
      and II NSCLC and confirmed the role of adjuvant chemotherapy as part of the
      treatment of these patients. The Lung Adjuvant Cisplatin Evaluation program, a
      pooled analysis of all recent platin-based adjuvant trials, and the IALT-Bio
      study, which will investigate over 30 markers in the IALT patients' specimens,
      should allow us to better define the populations more likely to benefit from
      postoperative chemotherapy.

PMID- 16000607
TI  - Patient subsets benefiting from adjuvant therapy following surgical resection of
      non-small cell lung cancer.
AB  - Adjuvant chemotherapy is the standard of therapy for some patients with stages I,
      II, and III breast and colon cancer. The therapeutic efficacy of adjuvant
      chemotherapy following surgical resection of early stage non-small cell lung
      cancer (NSCLC) has been less clear. A meta-analysis was reported in 1995 of
      patients who underwent surgical resection for early stage NSCLC and were then
      randomized to either observation or chemotherapy. This meta-analysis showed a 13%
      reduction in the hazard ratio of death, leading to a 5% absolute improvement in
      survival 5 years after the start of adjuvant cisplatin-based chemotherapy
      treatment compared with observation only. Multiple prospective randomized trials
      for patients with NSCLC were planned and undertaken to attempt to validate the
      observations of the meta-analysis. Six trials with > or =150 patients with early
      stage NSCLC (stages I-IIIA) on each arm have been reported in the last 2 years.
      Four of the six trials show a survival advantage for the patients with early
      stage NSCLC treated with adjuvant chemotherapy compared with those who underwent
      observation. The survival benefit in these four studies varies from a 4% to a 16%
      survival advantage at 4 to 5 years after the start of chemotherapy. The hazard
      ratio of death for the patients treated with chemotherapy ranged from 0.61 to
      0.86 compared with patients on observation. Thus, the information available at
      the current time supports the administration of chemotherapy for patients with
      stages IB and II NSCLC. Further research will be needed to define the role of
      adjuvant chemotherapy and its use in conjunction with chest radiotherapy for the
      treatment of patients with resected stages IA and IIIA NSCLC.

PMID- 16000608
TI  - The role of targeted agents in adjuvant therapy for non-small cell lung cancer.
AB  - The recent survival benefit of adjuvant chemotherapy in early stage non-small
      cell lung cancer provides optimism for the future success of targeted therapy in
      this setting. It is important that we begin to explore molecularly targeted
      agents in the adjuvant arena, but how best to accomplish this in the face of
      these new findings presents a challenge. Criteria for selecting promising
      targeted therapies and optimal trial designs to evaluate them expeditiously in
      the adjuvant setting are clearly needed.

PMID- 16000609
TI  - Study design issues and early stage non-small cell lung cancer.
AB  - The most common type of clinical trial in oncology enrolls patients with advanced
      disease. End points for phase II trials in advanced disease typically include
      response rate or time to progression, based upon the presumption that these may
      serve as surrogates for the ultimate end point of improved survival. Unique
      problems arise with the design of adjuvant trials, for which response rates
      clearly are not appropriate end points. In addition, survival is much longer,
      making rapid completion of phase III trials difficult. For lung cancer, the
      proportion of patients with stage I and II disease is much lower than with other
      types of cancer, and the absolute number of these patients is relatively low. To
      conduct large adjuvant trials in lung cancer more efficiently, we need to
      optimize our trials as much as possible. "Targeted therapies," by definition,
      inhibit a specific target, thus offering the theoretical advantage of enriching
      the patient population by restricting enrollment to patients whose tumor
      expresses the target of interest. Education of health care professionals
      regarding the benefits of adjuvant therapies, to decrease a sense of nihilism and
      to increase referrals, and international collaborations may also be necessary to
      increase accrual.

PMID- 16000610
TI  - The role of surgery in N2 non-small cell lung cancer.
AB  - Historical series document the poor survival (7-16% at 5 years) for patients with
      N2-positive, stage IIIA non-small cell lung cancer (NSCLC) treated with primary
      surgery. In 1994, two small randomized trials showed the superiority of induction
      chemotherapy followed by surgery over surgery alone for stage IIIA NSCLC. These
      findings, as well as subsequent studies showing the superiority of
      chemoradiotherapy over chemotherapy alone in nonoperable stage III disease,
      prompted investigations of preoperative chemoradiotherapy for N2-positive
      patients. As induction therapy improved, the use of resection in stage IIIA NSCLC
      was called into question. An Intergroup trial addressing this issue randomized
      392 patients to induction chemoradiotherapy followed by surgery versus definitive
      chemoradiotherapy. Surgery following induction chemoradiotherapy was associated
      with a significant improvement in progression-free survival and almost a 50%
      reduction in local failure. As distant relapse is common, survival is likely to
      be enhanced only in those patients who respond to the systemic arm of treatment.
      Identification of genetic or biochemical markers of response, minimally invasive
      techniques to pathologically restage, or improved statistical or chemosensitivity
      analyses are needed to enhance our ability to select patients who will benefit
      from resection.

PMID- 16000611
TI  - Surgical management of T3 and T4 lung cancer.
AB  - Locally advanced lung cancer (T(3) or T(4)) has a significantly worse prognosis
      than lower stage disease. However, this diagnosis is usually made radiologically,
      and experienced thoracic surgeons are familiar with the low radiologic to
      pathologic correlation in tumors that abut the great vessels, mediastinum, or
      chest wall. Commonly these tumors do not directly invade adjacent structures and
      are, in fact, T(1) or T(2) tumors that are resectable through standard
      techniques. Where there is no clearly evident invasion of unresectable
      structures, the patient should be given the benefit of the doubt and considered
      at a lower (resectable) stage until proven otherwise. The curability of T(3)
      tumors varies according to the involved site. A T(3)N(0) tumor involving the
      chest wall provides the most favorable prognosis among the resected T(3) lesions,
      with a 5-year survival of >50% in lymph node-negative patients if resection is
      complete. Palliative incomplete resections of T(4) disease, in which tumor has
      invaded mediastinal structures, have not shown any survival benefit and are
      associated with very high morbidity and mortality. However, patients with limited
      invasion of the carina, left atrium, superior vena cava, or pulmonary artery may
      be able to be completely resected despite their T(4) classification. Surgical
      resection remains an important part of the therapy for patients with locally
      advanced lung cancer. Modern techniques of chest wall resection and
      reconstruction and bronchoplastic procedures allow complete resection of locally
      advanced tumors with favorable 5-year survival rates and low morbidity and
      mortality.

PMID- 16000612
TI  - Concurrent chemoradiotherapy for unresectable stage III non-small cell lung
      cancer.
AB  - Over the last two decades, several approaches to multimodality therapy have been
      investigated in patients with advanced unresectable non-small cell lung cancer.
      These include induction chemotherapy and concurrent chemoradiotherapy. Both
      approaches have been shown to be superior to radiation therapy alone. However, in
      several randomized trials, concomitant chemoradiotherapy was shown to be superior
      to the induction chemotherapy approach. It has been hypothesized that the
      addition of systemic dose sequential chemotherapy to concurrent
      chemoradiotherapy, either as induction or as consolidation chemotherapy, might
      further improve survival rates. Recently, the Cancer and Leukemia Group B
      reported on a randomized phase III trial directly evaluating the addition of two
      cycles of carboplatin and paclitaxel to concurrent chemoradiotherapy. In this
      study, induction chemotherapy failed to further improve survival rates of
      concurrent chemoradiotherapy. A previously conducted randomized phase II study
      also suggested no benefit from the addition of induction chemotherapy to
      concomitant chemoradiotherapy. Favorable phase II data have been published
      supporting the use of consolidation chemotherapy. However, to date, no large
      randomized study evaluating a possible benefit from consolidation chemotherapy
      has been completed. In addition to evaluating optimal sequencing strategies of
      combined modality therapy, current investigations are also focusing on the
      integration of novel agents, including chemotherapeutic and targeted therapies.
      Currently ongoing trials involving novel approaches are reviewed here.

PMID- 16000613
TI  - Sequential platinum-based chemotherapy-thoracic radiotherapy in early stage non
      small cell lung cancer.
AB  - Combined chemoradiotherapy (CTRT) is intended to reduce the risk of local
      regional recurrence and distant relapse in patients with early stage non-small
      cell lung cancer (NSCLC). Sequential CTRT allows full doses of each modality
      while avoiding the additive toxicity that occurs with concurrent therapy. This
      review will encompass studies in the three main settings where sequential CTRT
      has been applied in early stage NSCLC: as adjuvant therapy after resection, as
      neoadjuvant chemotherapy and surgery followed by radiotherapy, and in
      unresectable stage III disease.

PMID- 16000614
TI  - Integration of novel therapeutics into combined modality therapy of locally
      advanced non-small cell lung cancer.
AB  - Novel therapeutic agents (NTA) directed against a wide array of newly described
      molecular targets are now entering clinical investigation, many in the treatment
      of non-small cell lung cancer (NSCLC). The great majority of these clinical
      trials have been directed toward patients with advanced stage (metastatic)
      disease. More recently, study of NTAs has turned toward earlier-stage disease.
      Locally advanced, or stage III, NSCLC represents a large and heterogeneous group
      of patients and several clinically distinct substages. During the last 15 years,
      randomized clinical trials have shown improved survival with sequential
      chemoradiation compared with radiation alone and, more recently, the superiority
      of concurrent versus sequential chemoradiation. As NTAs have increasingly shown
      clinical activity against NSCLC, questions of how to incorporate them into
      clinical trials in stage III disease, whether they should be given together with
      radiotherapy, substituting for chemotherapy, or whether they should be added to
      current chemoradiation strategies, all remain as issues. Here, we describe
      conceptual issues, preclinical rationale, and ongoing or planned clinical trials
      incorporating NTAs into current treatment paradigms for unresectable stage III
      NSCLC.

PMID- 16000615
TI  - Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1.
AB  - "Fierce" mice, homozygous for the deletion of nuclear receptor 2E1 (NR2E1), show
      abnormal brain-eye development and pathological aggression. To evaluate
      functional equivalency between mouse and human NR2E1, we generated mice
      transgenic for a genomic clone spanning the human NR2E1 locus and bred these
      animals to fierce mice deleted for the corresponding mouse gene. In fierce
      mutants carrying human NR2E1, structural brain defects were eliminated and eye
      abnormalities ameliorated. Excitingly, behavior in these "rescue" mice was
      indistinguishable from controls. Because no artificial promoter was used to drive
      transgene expression, promoter and regulatory elements within the human NR2E1
      clone are functional in mouse. Normal behavior in rescue animals suggests that
      mechanisms underlying the behavioral abnormalities in fierce mice may also be
      conserved in humans. Our data support the hypothesis that variation at NR2E1 may
      contribute to human behavioral disorders. Use of this rescue paradigm with other
      genes will permit the direct evaluation of human genes hypothesized to play a
      causal role in psychiatric disease but for which evidence is lacking or
      equivocal.

PMID- 16000616
TI  - Reducing cerebral microvascular amyloid-beta protein deposition diminishes
      regional neuroinflammation in vasculotropic mutant amyloid precursor protein
      transgenic mice.
AB  - Cerebral microvascular amyloid-beta (Abeta) protein deposition is emerging as an
      important contributory factor to neuroinflammation and dementia in Alzheimer's
      disease and related familial cerebral amyloid angiopathy disorders. In
      particular, cerebral microvascular amyloid deposition, but not parenchymal
      amyloid, is more often correlated with dementia. Recently, we generated
      transgenic mice (Tg-SwDI) expressing the vasculotropic Dutch (E693Q)/Iowa (D694N)
      mutant human Abeta precursor protein in brain that accumulate abundant cerebral
      microvascular fibrillar amyloid deposits. In the present study, our aim was to
      assess how the presence or absence of fibrillar Abeta deposition in the cerebral
      microvasculature affects neuroinflammation in Tg-SwDI mice. Using Tg-SwDI mice
      bred onto an apolipoprotein E gene knock-out background, we found a strong
      reduction of fibrillar cerebral microvascular Abeta deposition, which was
      accompanied by a sharp decrease in microvascular-associated neuroinflammatory
      cells and interleukin-1beta levels. Quantitative immunochemical measurements
      showed that this reduction of the neuroinflammation occurred in the absence of
      lowering the levels of total Abeta40/Abeta42 or soluble Abeta oligomers in brain.
      These findings suggest that specifically reducing cerebral microvascular
      fibrillar Abeta deposition, in the absence of lowering either the total amount of
      Abeta or soluble Abeta oligomers in brain, may be sufficient to ameliorate
      microvascular amyloid-associated neuroinflammation.

PMID- 16000617
TI  - Gap-junctional coupling between neurogliaform cells and various interneuron types
      in the neocortex.
AB  - Electrical synapses contribute to the generation of synchronous activity in
      neuronal networks. Several types of cortical GABAergic neurons acting via
      postsynaptic GABA(A) receptors also form electrical synapses with interneurons of
      the same class, suggesting that synchronization through gap junctions could be
      limited to homogenous interneuron populations. Neurogliaform cells elicit
      combined GABA(A) and GABA(B) receptor-mediated postsynaptic responses in cortical
      pyramidal cells, but it is not clear whether neurogliaform cells are involved in
      networks linked by electrical coupling. We recorded from pairs, triplets, and
      quadruplets of cortical neurons in layers 2 and 3 of rat somatosensory cortex
      (postnatal day 20-35). Neurogliaform cells eliciting slow IPSPs on pyramidal
      cells also triggered divergent electrical coupling potentials on interneurons.
      Neurogliaform cells were electrically coupled to other neurogliaform cells,
      basket cells, regular-spiking nonpyramidal cells, to an axoaxonic cell, and to
      various unclassified interneurons showing diverse firing patterns and morphology.
      Electrical interactions were mediated by one or two electron microscopically
      verified gap junctions linking the somatodendritic domain of the coupled cells.
      Our results suggest that neurogliaform cells have a unique position in the
      cortical circuit. Apart from eliciting combined GABA(A) and GABA(B) receptor
      mediated inhibition on pyramidal cells, neurogliaform cells establish electrical
      synapses and link multiple networks formed by gap junctions restricted to a
      particular class of interneuron. Widespread electrical connections might enable
      neurogliaform cells to monitor the activity of different interneurons acting on
      GABA(A) receptors at various regions of target cells.

PMID- 16000618
TI  - Dual presynaptic control by ATP of glutamate release via facilitatory P2X1,
      P2X2/3, and P2X3 and inhibitory P2Y1, P2Y2, and/or P2Y4 receptors in the rat
      hippocampus.
AB  - ATP is released in a vesicular manner from nerve terminals mainly at higher
      stimulation frequencies. There is a robust expression of ATP (P2) receptors in
      the brain, but their role is primarily unknown. We report that ATP analogs
      biphasically modulate the evoked release of glutamate from purified nerve
      terminals of the rat hippocampus, the facilitation being mediated by P2X1,
      P2X2/3, and P2X3 [antagonized by 8-(benzamido)naphthalene-1,3,5-trisulfonate and
      2',3'-O-(2,4,6-trinitrophenyl)-ATP] and the inhibition by P2Y1, P2Y2, and/or P2Y4
      [antagonized by reactive blue 2 and 2'deoxy-N6-methyladenosine-3',5'-bisphosphate
      and mimicked by P1-(urinine 5'-),P4-(inosine 5'-) tetraphosphate and 2-methylthio
      ADP] receptors. The combination of single-cell PCR analysis of rat hippocampal
      pyramidal neurons, Western blot analysis of purified presynaptic active zone
      fraction, and immunocytochemical analysis of hippocampal glutamatergic terminals
      revealed that the P2 receptors expressed in glutamatergic neurons, located in the
      active zone and in glutamatergic terminals, were precisely P2X1, P2X2, and P2X3
      subunits and P2Y1, P2Y2, and P2Y4 receptors. This provides coincident functional
      and molecular evidence that P2 receptors are present and act presynaptically as a
      modulatory system controlling hippocampal glutamate release.

PMID- 16000619
TI  - cAMP responsive element-binding protein phosphorylation is necessary for
      perirhinal long-term potentiation and recognition memory.
AB  - We established the importance of phosphorylation of cAMP responsive element
      binding protein (CREB) to both the familiarity discrimination component of long
      term recognition memory and plasticity within the perirhinal cortex of the
      temporal lobe. Adenoviral transduction of perirhinal cortex (and adjacent visual
      association cortex) with a dominant-negative inhibitor of CREB impaired the
      preferential exploration of novel over familiar objects at a long (24 h) but not
      a short (15 min) delay, disrupted the normal reduced activation of perirhinal
      neurons to familiar compared with novel pictures, and impaired long-term
      potentiation of synaptic transmission in perirhinal slices. The consistency of
      these effects across the behavioral, systems, and cellular levels of analysis
      provides strong evidence for involvement of CREB phosphorylation in synaptic
      plastic processes within perirhinal cortex necessary for long-term recognition
      memory.

PMID- 16000621
TI  - Periodic high-conductance states in spinal neurons during scratch-like network
      activity in adult turtles.
AB  - Intense synaptic activity may alter the response properties of neurons in highly
      interconnected networks. Here we investigate whether the excitability and the
      intrinsic response properties of neurons in the spinal cord are affected by the
      increased synaptic conductance during functional network activity. Scratch
      episodes were induced by mechanical stimulation in the isolated carapace-spinal
      cord preparation from the adult turtle. Intracellular recordings revealed a
      dramatic increase in synaptic activity in interneurons and motoneurons during
      scratch activity. Superimposed slow depolarizing waves were phase-related to the
      rhythmic bouts of spike activity in the hip flexor nerve. The increase in
      synaptic conductance in interneurons and motoneurons varied with the scratch
      rhythm. During individual episodes, the conductance shifted smoothly with the
      scratch rhythm from near-resting levels to levels two to four times higher. In
      slice experiments, we found that even moderate increases in the conductance of
      motoneurons suppressed the slow afterhyperpolarization and the plateau
      potentials. We conclude that the excitability and the intrinsic response
      properties of spinal neurons are periodically quenched by high synaptic
      conductance during functional network activity.

PMID- 16000620
TI  - Globus pallidus neurons dynamically regulate the activity pattern of subthalamic
      nucleus neurons through the frequency-dependent activation of postsynaptic GABAA
      and GABAB receptors.
AB  - Reciprocally connected GABAergic neurons of the globus pallidus (GP) and
      glutamatergic neurons of the subthalamic nucleus (STN) are a putative generator
      of pathological rhythmic burst firing in Parkinson's disease (PD). Burst firing
      of STN neurons may be driven by rebound depolarization after barrages of GABA(A)
      receptor (GABA(A)R)-mediated IPSPs arising from pallidal fibers. To determine the
      conditions under which pallidosubthalamic transmission activates these and other
      postsynaptic GABARs, a parasagittal mouse brain slice preparation was developed
      in which pallidosubthalamic connections were preserved. Intact connectivity was
      first confirmed through the injection of a neuronal tracer into the GP. Voltage
      clamp and gramicidin-based perforated-patch current-clamp recordings were then
      used to study the relative influences of GABA(A)R- and GABA(B)R-mediated
      pallidosubthalamic transmission on STN neurons. Spontaneous phasic, but not
      tonic, activation of postsynaptic GABA(A)Rs reduced the frequency and disrupted
      the rhythmicity of autonomous firing in STN neurons. However, postsynaptic
      GABA(B)Rs were only sufficiently activated to impact STN firing when
      pallidosubthalamic transmission was elevated or pallidal fibers were
      synchronously activated by electrical stimulation. In a subset of neurons,
      rebound burst depolarizations followed high-frequency, synchronous stimulation of
      pallidosubthalamic fibers. Although GABA(B)R-mediated hyperpolarization was
      itself sufficient to generate rebound bursts, coincident activation of
      postsynaptic GABA(A)Rs produced longer and more intense burst firing. These
      findings elucidate a novel route through which burst activity can be generated in
      the STN, and suggest that GABARs on STN neurons could act in a synergistic manner
      to generate abnormal burst activity in PD.

PMID- 16000622
TI  - Cooperative activation of D1 and D2 dopamine receptors enhances a
      hyperpolarization-activated inward current in layer I interneurons.
AB  - Layer I of the neocortex comprises axonal processes from widespread regions of
      the brain and a unique population of GABAergic interneurons. Dopamine is known to
      directly depolarize layer I interneurons, but the underlying mechanism is
      unclear. Using whole-cell recording techniques in neocortical brain slices, we
      have examined how dopamine increases excitability of layer I interneurons in
      postnatal day 7-11 rats. Dopamine (30 microm) caused a 10 mV depolarization of
      layer I neurons. Paradoxically, neither the D1-like receptor agonist 6-chloro
      2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide (SKF81297) (1-10
      microm) nor the D2-like agonist quinpirole (10 microm) produced a significant
      depolarization. Depolarization was observed when SKF81297 and quinpirole were
      coapplied. When G-protein betagamma subunits were included in the recording
      pipette, D1 but not D2 agonists depolarized layer I neurons. Bath application of
      4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride, a specific
      blocker of inwardly rectifying hyperpolarization-activated current (Ih) channels,
      hyperpolarized the neurons and occluded the action of dopamine. Voltage-clamp
      analysis demonstrated that dopamine increased the amplitude and shifted the
      voltage dependence of activation of Ih. These results indicate that Ih
      contributes to the resting potential of layer I interneurons and is subject to
      modulation by dopamine.

PMID- 16000623
TI  - Progressive degeneration of human mesencephalic neuron-derived cells triggered by
      dopamine-dependent oxidative stress is dependent on the mixed-lineage kinase
      pathway.
AB  - Models of Parkinson's disease (PD) based on selective neuronal death have been
      used to study pathogenic mechanisms underlying nigral cell death and in some
      instances to develop symptomatic therapies. For validation of putative
      neuroprotectants, a model is desirable in which the events leading to
      neurodegeneration replicate those occurring in the disease. We developed a human
      in vitro model of PD based on the assumption that dysregulated cytoplasmic
      dopamine levels trigger cell loss in this disorder. Differentiated human
      mesencephalic neuron-derived cells were exposed to methamphetamine (METH) to
      promote cytoplasmic dopamine accumulation. In the presence of elevated iron
      concentrations, as observed in PD, increased cytosolic dopamine led to oxidative
      stress, c-Jun N-terminal kinase (JNK) pathway activation, neurite degeneration,
      and eventually apoptosis. We examined the role of the mixed-lineage kinases
      (MLKs) in this complex degenerative cascade by using the potent inhibitor 3,9
      bis[(ethylthio)methyl]-K-252a (CEP1347). Inhibition of MLKs not only prevented
      FeCl2+/METH-induced JNK activation and apoptosis but also early events such as
      neurite degeneration and oxidative stress. This broad neuroprotective action of
      CEP1347 was associated with increased expression of an oxidative stress-response
      modulator, activating transcription factor 4. As a functional consequence,
      transcription of the cystine/glutamate and glycine transporters, cellular cystine
      uptake and intracellular levels of the redox buffer glutathione were augmented.
      In conclusion, this new human model of parkinsonian neurodegeneration has the
      potential to yield new insights into neurorestorative therapeutics and suggests
      that enhancement of cytoprotective mechanisms, in addition to blockade of
      apoptosis, may be essential for disease modulation.

PMID- 16000624
TI  - Noradrenergic modulation of emotion-induced forgetting and remembering.
AB  - We used a free-recall paradigm to establish a behavioral index of the retrograde
      and anterograde interference of emotion with episodic memory encoding. In two
      experiments involving 78 subjects, we show that negatively valenced items elicit
      retrograde amnesia, whereas positively valenced items elicit retrograde
      hypermnesia. These data indicate item valence is critical in determining
      retrograde amnesia and retrograde hypermnesia. In contrast, we show that item
      arousal induces an anterograde amnesic effect, consistent with the idea that a
      valence-evoked arousal mechanism compromises anterograde episodic encoding.
      Randomized double-blind administration of the beta-adrenoceptor antagonist
      propranolol compared with the selective norepinephrine (NE) reuptake-inhibitor
      reboxetine, and placebo, demonstrated that the magnitude of this emotional
      amnesia and hypermnesia can be upregulated and downregulated as a function of
      emotional arousal and central NE signaling. We conclude that a differential
      processing of emotional arousal and valence influences how the brain remembers
      and forgets.

PMID- 16000625
TI  - Constitutively active cytoplasmic c-Jun N-terminal kinase 1 is a dominant
      regulator of dendritic architecture: role of microtubule-associated protein 2 as
      an effector.
AB  - Normal functioning of the nervous system requires precise regulation of dendritic
      shape and synaptic connectivity. Here, we report a severe impairment of dendritic
      structures in the cerebellum and motor cortex of c-Jun N-terminal kinase 1 (JNK1)
      deficient mice. Using an unbiased screen for candidate mediators, we identify the
      dendrite-specific high-molecular-weight microtubule-associated protein 2 (MAP2)
      as a JNK substrate in the brain. We subsequently show that MAP2 is phosphorylated
      by JNK in intact cells and that MAP2 proline-rich domain phosphorylation is
      decreased in JNK1-/- brain. We developed compartment-targeted JNK inhibitors to
      define whether a functional relationship exists between the physiologically
      active, cytosolic pool of JNK and dendritic architecture. Using these, we
      demonstrate that cytosolic, but not nuclear, JNK determines dendritic length and
      arbor complexity in cultured neurons. Moreover, we confirm that MAP2-dependent
      process elongation is enhanced after activation of JNK. Using JNK1-/- neurons, we
      reveal a dominant role for JNK1 over ERK in regulating dendritic arborization,
      whereas ERK only regulates dendrite shape under conditions in which JNK activity
      is low (JNK1-/- neurons). These results reveal a novel antagonism between JNK and
      ERK, potentially providing a mechanism for fine-tuning the dendritic arbor.
      Together, these data suggest that JNK phosphorylation of MAP2 plays an important
      role in defining dendritic architecture in the brain.

PMID- 16000626
TI  - Olfactory impairments in patients with unilateral cerebellar lesions are
      selective to inputs from the contralesional nostril.
AB  - Functional imaging studies of olfaction have consistently reported odorant
      induced activation of the cerebellum. However, the cerebellar role in olfaction
      remains unknown. We examined the olfactory and olfactomotor abilities of patients
      with unilateral cerebellar lesions, comparing performance within subjects across
      nostrils, as well as between subjects with age-matched and young controls.
      Regarding olfactory performance, initial testing revealed that patients had a
      contralesional impairment in olfactory identification but not olfactory detection
      threshold. However, when tested under conditions that prevented compensatory
      sniffing strategies, the patients also exhibited a contralesional olfactory
      detection impairment. Regarding olfactomotor function, a healthy olfactomotor
      system generates sniffs that are (1) sufficiently vigorous and (2) inversely
      proportional to odorant concentration in sniff mean airflow velocity, maximum
      airflow velocity, volume, and duration. Patients' sniffs were lower in overall
      airflow velocity and volume in comparison with control participants. Furthermore,
      reduced sniff velocity predicted poorer detection thresholds in patients.
      Finally, whereas young controls used concentration-dependent sniffs, there was a
      trend in that direction only for age-matched controls. Patients used sniffs that
      were concentration invariant. In conclusion, cerebellar lesions impacted
      olfactory and olfactomotor performance. These findings strongly implicate an
      olfactocerebellar pathway prominent in odor identification and detection that
      functionally connects each nostril primarily to the contralateral cerebellum.

PMID- 16000627
TI  - Off-line learning and the primary motor cortex.
AB  - We are all familiar with acquiring skills during practice, but skill can also
      continue to develop between practice sessions. These "off-line" improvements are
      frequently supported by sleep, but they can be time dependent when a skill is
      acquired unintentionally. The magnitude of these over-day and overnight
      improvements is similar, suggesting that a similar mechanism may support both
      types of off-line improvements. However, here we show that disruption of the
      primary motor cortex with repetitive transcranial magnetic stimulation blocks off
      line improvements over the day but not overnight. This suggests that a memory may
      be rescued overnight and subsequently enhanced or that different aspects of a
      skill, with differential dependencies on the primary motor cortex, are enhanced
      over day and overnight. Off-line improvements of similar magnitude are not
      supported by similar mechanisms; instead, the mechanisms engaged may depend on
      brain state.

PMID- 16000628
TI  - Synapse-specific regulation of AMPA receptor subunit composition by activity.
AB  - We examined the changes that arise when neurotransmitter release is inhibited in
      a subpopulation of hippocampal neurons in coculture with normally active
      neighbors. Subsets of neurons were presynaptically silenced by chronic expression
      of tetanus toxin light chain tagged with cyan fluorescent protein (TNTCFP).
      Surprisingly, silenced neurons formed as many presynaptic terminals as their
      active neighbors when grown together on glial microislands. However, silenced
      neurons could not recruit the AMPA-type glutamate receptor subunit GluR1 as
      efficiently when competing with active neighbors. The immunofluorescence
      intensity ratio of GluR1 at synaptic puncta versus shaft was reduced by 22%
      opposite TNTCFP-expressing terminals compared with active neighbors. In contrast,
      this effect is abolished when vesicular release is blocked in all neurons. Local
      presynaptic inhibition by TNTCFP did not change the synaptic level of the AMPA
      receptor subunits GluR2 or GluR2/3 or of the PSD95 (postsynaptic density 95)
      family scaffolding proteins. Thus, neurotransmitter release selectively regulates
      the AMPA receptor population on a synapse-by-synapse basis but is not essential
      for an axon to efficiently compete for synaptic territory in a simple model
      system. These results demonstrate precise input specificity of postsynaptic
      receptor composition via differential activity among neighbor synapses.

PMID- 16000629
TI  - Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic
      inhibition of excitatory transmission and vulnerability to cocaine seeking.
AB  - Withdrawal from chronic cocaine reduces extracellular glutamate levels in the
      nucleus accumbens by decreasing cystine/glutamate exchange (xc-). Activating xc-
      with N-acetylcysteine restores extracellular glutamate and prevents cocaine
      induced drug seeking. It was hypothesized that the activation of xc- prevents
      drug seeking by increasing glutamatergic tone on presynaptic group II
      metabotropic glutamate receptors (mGluR2/3) and thereby inhibiting excitatory
      transmission. In the first experiment, the capacity of glutamate derived from xc-
      to regulate excitatory transmission via mGluR2/3 was determined. Physiological
      levels of cystine (100-300 nm) were restored to acute tissue slices from the
      nucleus accumbens or prefrontal cortex. Cystine increased glutamate efflux and
      decreased miniature EPSC (mEPSC) and spontaneous EPSC (sEPSC) frequency as well
      as evoked EPSC amplitude. These effects of cystine were presynaptic, because
      there was no change in mEPSC or sEPSC amplitude, and an increase in the evoked
      EPSC paired-pulse facilitation ratio. The cystine-induced reduction in EPSCs was
      reversed by blocking either xc- or mGluR2/3. In the second experiment, blocking
      mGluR2/3 prevented the ability of N-acetylcystine to inhibit the reinstatement of
      drug seeking in rats trained to self-administer cocaine. These data demonstrate
      that nonsynaptic glutamate derived from xc- modulates synaptic glutamate release
      and thereby regulates cocaine-induced drug seeking.

PMID- 16000630
TI  - Intracortical origins of interocular suppression in the visual cortex.
AB  - The response of neurons in the primary visual cortex to an optimally oriented
      grating is usually suppressed quite dramatically when a second grating of, for
      example, orthogonal orientation is superimposed. Such "cross-orientation
      suppression" has been implicated in the generation of cortical orientation
      selectivity and local response normalization. Until recently, little experimental
      evidence was available concerning the neurophysiological substrate of this
      phenomenon, although an involvement of intracortical inhibition was commonly
      assumed. However, Freeman et al. (2002) proposed that cortical cross-orientation
      suppression is caused by suppression in the thalamus and depression at
      geniculocortical synapses. Here, we examine a dichoptic form of cross-orientation
      suppression, termed interocular suppression and thought to be involved in
      binocular rivalry (Sengpiel et al., 1995a). We show that its dependency on the
      drift rate of the suppressing stimulus is consistent with a cortical origin;
      unlike monocular cross-orientation suppression, it cannot be evoked by very fast
      moving stimuli. Moreover, we find that previous adaptation to the orthogonal
      stimulus essentially eliminates interocular suppression. Because adaptation is a
      cortical phenomenon, this result also argues in favor of a cortical locus of
      suppression, again unlike monocular cross-orientation suppression, which is not
      affected by adaptation to the suppressor (Freeman et al., 2002). Finally,
      interocular suppression is greatly reduced in the presence of the GABA antagonist
      bicuculline. Together, our study demonstrates that interocular suppression is
      substantially different from monocular cross-orientation suppression and is
      mediated by inhibitory circuitry within the visual cortex.

PMID- 16000631
TI  - A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from
      proteolysis and neurons from apoptosis in transient focal cerebral ischemia.
AB  - Neuronal cell death occurs during many neurodegenerative disorders and stroke.
      The aberrant, excessive activity of matrix metalloproteinases (MMPs), especially
      MMP-9, contributes directly to neuron apoptosis and brain damage (Rosenberg et
      al., 1996; Asahi et al., 2001; Gu et al., 2002; Horstmann et al., 2003). We
      determined that MMP-9 degrades the extracellular matrix protein laminin and that
      this degradation induces neuronal apoptosis in a transient focal cerebral
      ischemia model in mice. We also determined that the highly specific thiirane
      gelatinase inhibitor SB-3CT blocks MMP-9 activity, including MMP-9-mediated
      laminin cleavage, thus rescuing neurons from apoptosis. We conclude that MMP-9 is
      a highly promising drug target and that SB-3CT derivatives have significant
      therapeutic potential in stroke patients.

PMID- 16000632
TI  - Functionally segregated neural substrates for arbitrary audiovisual paired
      association learning.
AB  - To clarify the neural substrates and their dynamics during crossmodal association
      learning, we conducted functional magnetic resonance imaging (MRI) during
      audiovisual paired-association learning of delayed matching-to-sample tasks.
      Thirty subjects were involved in the study; 15 performed an audiovisual paired
      association learning task, and the remainder completed a control visuo-visual
      task. Each trial consisted of the successive presentation of a pair of stimuli.
      Subjects were asked to identify predefined audiovisual or visuo-visual pairs by
      trial and error. Feedback for each trial was given regardless of whether the
      response was correct or incorrect. During the delay period, several areas showed
      an increase in the MRI signal as learning proceeded: crossmodal activity
      increased in unimodal areas corresponding to visual or auditory areas, and
      polymodal responses increased in the occipitotemporal junction and
      parahippocampal gyrus. This pattern was not observed in the visuo-visual
      intramodal paired-association learning task, suggesting that crossmodal
      associations might be formed by binding unimodal sensory areas via polymodal
      regions. In both the audiovisual and visuo-visual tasks, the MRI signal in the
      superior temporal sulcus (STS) in response to the second stimulus and feedback
      peaked during the early phase of learning and then decreased, indicating that the
      STS might be key to the creation of paired associations, regardless of stimulus
      type. In contrast to the activity changes in the regions discussed above, there
      was constant activity in the frontoparietal circuit during the delay period in
      both tasks, implying that the neural substrates for the formation and storage of
      paired associates are distinct from working memory circuits.

PMID- 16000633
TI  - Central and sensory contributions to the activation and organization of muscle
      synergies during natural motor behaviors.
AB  - Previous studies have suggested that the motor system may simplify control by
      combining a small number of muscle synergies represented as activation profiles
      across a set of muscles. The role of sensory feedback in the activation and
      organization of synergies has remained an open question. Here, we assess to what
      extent the motor system relies on centrally organized synergies activated by
      spinal and/or supraspinal commands to generate motor outputs by analyzing
      electromyographic (EMG) signals collected from 13 hindlimb muscles of the
      bullfrog during swimming and jumping, before and after deafferentation. We first
      established that, for both behaviors, the intact and deafferented data sets
      possess low and similar dimensionalities. Subsequently, we used a novel
      reformulation of the non-negative matrix factorization algorithm to
      simultaneously search for synergies shared by, and synergies specific to, the
      intact and deafferented data sets. Most muscle synergies were identified as
      shared synergies, suggesting that EMGs of locomotor behaviors are generated
      primarily by centrally organized synergies. Both the amplitude and temporal
      patterns of the activation coefficients of most shared synergies, however, were
      altered by deafferentation, suggesting that sensory inflow modulates activation
      of those centrally organized synergies. For most synergies, effects of
      deafferentation on the activation coefficients were not consistent across frogs,
      indicating substantial interanimal variability of feedback actions. We speculate
      that sensory feedback might adapt recruitment of muscle synergies to behavioral
      constraints, and the few synergies specific to the intact or deafferented states
      might represent afferent-specific modules or feedback reorganization of spinal
      neuronal networks.

PMID- 16000634
TI  - On the computations analyzing natural optic flow: quantitative model analysis of
      the blowfly motion vision pathway.
AB  - For many animals, including humans, the optic flow generated on the eyes during
      locomotion is an important source of information about self-motion and the
      structure of the environment. The blowfly has been used frequently as a model
      system for experimental analysis of optic flow processing at the microcircuit
      level. Here, we describe a model of the computational mechanisms implemented by
      these circuits in the blowfly motion vision pathway. Although this model was
      originally proposed based on simple experimenter-designed stimuli, we show that
      it is also capable to quantitatively predict the responses to the complex dynamic
      stimuli a blowfly encounters in free flight. In particular, the model visual
      system exploits the active saccadic gaze and flight strategy of blowflies in a
      similar way, as does its neuronal counterpart. The model circuit extracts
      information about translation velocity in the intersaccadic intervals and thus,
      indirectly, about the three-dimensional layout of the environment. By stepwise
      dissection of the model circuit, we determine which of its components are
      essential for these remarkable features. When accounting for the responses to
      complex natural stimuli, the model is much more robust against parameter changes
      than when explaining the neuronal responses to simple experimenter-defined
      stimuli. In contrast to conclusions drawn from experiments with simple stimuli,
      optimization of the parameter set for different segments of natural optic flow
      stimuli do not indicate pronounced adaptational changes of these parameters
      during long-lasting stimulation.

PMID- 16000636
TI  - A variant C178T in the regulatory region of the serotonin receptor gene HTR3A
      modulates neural activation in the human amygdala.
AB  - Converging evidence in neurophysiological and neuroimaging studies has suggested
      that the limbic and prefrontal systems play important roles in emotion and
      cognition. These structures are activated when we see a human face, assuming that
      we automatically evaluate the biological significance of the stimuli. The
      serotonin (5-HT) system within the brain has been tied to various behaviors such
      as mood and anxiety and to the biology of neuropsychiatric disorders. To
      investigate the link between the 5-HT system and limbic/prefrontal activity,
      normal subjects (n = 26) who underwent functional magnetic resonance imaging and
      faced recognition tasks were genotyped for the single nucleotide polymorphism
      C178T in the regulatory region of the serotonin receptor type 3 gene (HTR3A). We
      found that the subjects with C/C alleles had greater activity in the amygdala and
      dorsal and medial prefrontal cortices than those with C/T alleles. The C/C group
      also showed a faster reaction time during the task than the C/T group. The
      temperamental predisposition of the subjects had a significant correlation with
      brain activity in the C/C group. The genotype effect in the right amygdala and
      prefrontal cortex was largest during the first run of the experiment. These
      results indicate that the C178T variation in the HTR3A has a critical influence
      on the amygdaloid activity and on human face processing, probably through
      regulation of the receptor expression. The present study may contribute to
      elucidating a possible link among genes, the brain, and behavior in normal
      populations and may help reveal the biological basis of neuropsychiatric
      disorders.

PMID- 16000635
TI  - Adult motor neuron apoptosis is mediated by nitric oxide and Fas death receptor
      linked by DNA damage and p53 activation.
AB  - The mechanisms of injury- and disease-related degeneration of motor neurons (MNs)
      need clarification. Unilateral avulsion of the sciatic nerve in the mouse induces
      apoptosis of spinal MNs that is p53 and Bax dependent. We tested the hypothesis
      that MN apoptosis is Fas death receptor dependent and triggered by nitric oxide
      (NO)- and superoxide-mediated damage to DNA. MNs in mice lacking functional Fas
      receptor and Fas ligand were protected from apoptosis. Fas protein levels and
      cleaved caspase-8 increased in MNs after injury. Fas upregulation was p53
      dependent. MNs in mice deficient in neuronal NO synthase (nNOS) and inducible NOS
      (iNOS) resisted apoptosis. After injury, MNs increased nNOS protein but decreased
      iNOS protein; however, iNOS contributed more than nNOS to basal and injury
      induced levels of NADPH diaphorase activity in MNs. NO and peroxynitrite (ONOO-)
      fluorescence increased in injured MNs, as did nitrotyrosine staining of MNs. DNA
      damage, assessed as 8-hydroxy-2-deoxyguanosine and single-stranded DNA,
      accumulated within injured MNs and was attenuated by nNOS and iNOS deficiency.
      nNOS deficiency increased DNA repair protein oxoguanine DNA-glycosylase, whereas
      iNOS deficiency blocked diaphorase activity. MN apoptosis was blocked by the
      antioxidant Trolox and by overexpression of wild-type human superoxide dismutase
      1 (SOD1). In contrast, injured MNs in mice harboring mutant human SOD1 had
      upregulated Fas and iNOS, escalated DNA damage, and accelerated and increased MN
      degeneration and underwent necrosis instead of apoptosis. Thus, adult spinal MN
      apoptosis is mediated by upstream NO and ONOO- genotoxicity and downstream p53
      and Fas activation and is shifted to necrosis by mutant SOD1.

PMID- 16000637
TI  - Identification of dopaminergic neurons of nigral and ventral tegmental area
      subtypes in grafts of fetal ventral mesencephalon based on cell morphology,
      protein expression, and efferent projections.
AB  - Transplants of fetal ventral mesencephalic tissue are known to contain a mixture
      of two major dopamine (DA) neuron types: the A9 neurons of the substantia nigra
      pars compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA).
      Previous studies have suggested that these two DA neuron types may differ in
      their growth characteristics, but, because of technical limitations, it has so
      far been difficult to identify the two subtypes in fetal ventral mesencephalon
      (VM) grafts and trace their axonal projections. Here, we have made use of a
      transgenic mouse expressing green fluorescent protein (GFP) under the tyrosine
      hydroxylase promoter. The expression of the GFP reporter allowed for
      visualization of the grafted DA neurons and their axonal projections within the
      host brain. We show that the SNpc and VTA neuron subtypes in VM grafts can be
      identified on the basis of their morphology and location within the graft, and
      their expression of a G-protein-gated inwardly rectifying K+ channel subunit
      (Girk2) and calbindin, respectively, and also that the axonal projections of the
      two DA neuron types are markedly different. By retrograde axonal tracing, we show
      that dopaminergic innervation of the striatum is derived almost exclusively from
      the Girk2-positive SNpc cells, whereas the calbindin-positive VTA neurons project
      to the frontal cortex and probably also other forebrain areas. The results
      suggest the presence of axon guidance and target recognition mechanisms in the DA
      denervated forebrain that can guide the growing axons to their appropriate
      targets and indicate that cell preparations used for cell replacement in
      Parkinson's disease will be therapeutically useful only if they contain cells
      capable of generating the correct nigral DA neuron phenotype.

PMID- 16000638
TI  - Dynamic regulation of Na(+)-K(+)-2Cl(-) cotransporter surface expression by PKC
      {epsilon} in Cl(-)--secretory epithelia.
AB  - In secretory epithelia, activation of PKC by phorbol ester and carbachol
      negatively regulates Cl(-) secretion, the transport event of secretory diarrhea.
      Previous studies have implicated the basolateral Na(+)-K(+)-2Cl(-) cotransporter
      (NKCC1) as a target of PKC-dependent inhibition of Cl(-) secretion. In the
      present study, we examined the regulation of surface expression of NKCC1 in
      response to the activation of PKC. Treatment of confluent T84 intestinal
      epithelial cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate
      (PMA) reduced the amount of NKCC1 accessible to basolateral surface
      biotinylation. Loss of cell surface NKCC1 was due to internalization as shown by
      1) the resistance of biotinylated NKCC1 to surface biotin stripping after
      incubation with PMA and 2) indirect immunofluorescent labeling. PMA-induced
      internalization of NKCC1 is dependent on the epsilon-isoform of PKC as determined
      on the basis of sensitivity to a panel of PKC inhibitors. The effect of PMA on
      surface expression of NKCC1 was specific because PMA did not significantly alter
      the amount of Na(+)-K(+)-ATPase or E-cadherin available for surface
      biotinylation. After extended PMA exposure (>2 h), NKCC1 became degraded in a
      proteasome-dependent fashion. Like PMA, carbachol reduced the amount of NKCC1
      accessible to basolateral surface biotinylation in a PKC-epsilon-dependent
      manner. However, long-term exposure to carbachol did not result in degradation of
      NKCC1; rather, NKCC1 that was internalized after exposure to carbachol was
      recycled back to the cell membrane. PKC-epsilon-dependent alteration of NKCC1
      surface expression represents a novel mechanism for regulating Cl(-) secretion.

PMID- 16000639
TI  - (+)Insert smooth muscle myosin heavy chain (SM-B) isoform expression in human
      tissues.
AB  - Two smooth muscle myosin heavy chain isoforms differ in their amino terminus by
      the presence [(+)insert] or absence [(-)insert] of a seven-amino acid insert.
      Animal studies show that the (+)insert isoform is predominantly expressed in
      rapidly contracting phasic muscle and the (-)insert isoform is mostly found in
      slowly contracting tonic muscle. The expression of the (+)insert isoform has
      never been demonstrated in human smooth muscle. We hypothesized that the
      (+)insert isoform is present in humans and that its expression is commensurate
      with the organ's functional requirements. We report, for the first time, the
      sequence of the human (+)insert isoform and quantification of its expression by
      real-time PCR and Western blot analysis in a panel of human organs. The (+)insert
      isoform mRNA and protein expression levels are significantly greater in small
      intestine compared with all organs studied except for trachea and are
      significantly greater in trachea compared with uterus and aorta. To assess the
      functional significance of this differential myosin isoform expression between
      organs, we measured the rate of actin filament movement (nu(max)) when propelled
      by myosin purified from rat organs, because the rat and human inserts are
      identical and their remaining sequences show 93% identity. nu(max) exhibits a
      rank correlation from the most tonic to the most phasic organ. The selective
      expression of the (+)insert isoform observed among human organs suggests that it
      is an important determinant of tissue shortening velocity. A differential
      expression of the (+)insert isoform could also account for altered contractile
      properties observed in human pathology.

PMID- 16000640
TI  - Spatiotemporal analysis of exocytosis in mouse parotid acinar cells.
AB  - Exocrine cells of the digestive system are specialized to secrete protein and
      fluid in response to neuronal and/or hormonal input. Although morphologically
      similar, parotid and pancreatic acinar cells exhibit important functional
      divergence in Ca(2+) signaling properties. To address whether there are
      fundamental differences in exocytotic release of digestive enzyme from exocrine
      cells of salivary gland versus pancreas, we applied electrophysiological and
      optical methods to investigate spatial and temporal characteristics of zymogen
      containing secretory granule fusion at the single-acinar cell level by direct or
      agonist-induced Ca(2+) and cAMP elevation. Temporally resolved membrane
      capacitance measurements revealed that two apparent phases of exocytosis were
      induced by Ca(2+) elevation: a rapidly activated initial phase that could not be
      resolved as individual fusion events and a second phase that was activated after
      a delay, increased in a staircaselike fashion, was augmented by cAMP elevation,
      and likely reflected both sequential compound and multivesicular fusion of
      zymogen-containing granules. Optical measurements of exocytosis with time
      differential imaging analysis revealed that zymogen granule fusion was induced
      after a minimum delay of approximately 200 ms, occurred initially at apical and
      basolateral borders of acinar cells, and under strong stimulation proceeded from
      apical pole to deeper regions of the cell interior. Zymogen granule fusions
      appeared to coordinate subsequent fusions and produced persistent structures that
      generally lasted several minutes. In addition, parotid gland slices were used to
      assess secretory dynamics in a more physiological context. Parotid acinar cells
      were shown to exhibit both similar and divergent properties compared with the
      better-studied pancreatic acinar cell regarding spatial organization and kinetics
      of exocytotic fusion of zymogen granules.

PMID- 16000648
TI  - Dacron-covered stent-grafts in transjugular intrahepatic portosystemic shunts:
      initial experience.
AB  - PURPOSE: To retrospectively review the authors' experience with use of a Dacron
      covered stent-graft in transjugular intrahepatic postosystemic shunts (TIPS).
      MATERIALS AND METHODS: The need for internal review board approval was waived.
      Informed consent was obtained from all patients. The study was compliant with the
      Health Insurance Portability and Accountability Act. A retrospective analysis was
      performed of 16 patients who received a Dacron-covered stent-graft during
      revision or de novo creation of TIPS. There were 13 men and three women aged 44
      80 years (mean age, 61 years). Primary unassisted and assisted patency rates and
      secondary patency rates were estimated. The primary unassisted patency of
      patients who underwent de novo placement of stent-grafts (n = 10) was compared
      with that of patients with stent-grafts placed during shunt revision (n = 6); in
      all patients, stent-grafts were placed within stents. Primary unassisted patency
      was also compared between patients in whom the covered stent was confined to the
      parenchymal tract (n = 7) and those in whom the stent extended 1 cm or more into
      the portal vein (n = 9). Patency was estimated with the Kaplan-Meier method, and
      group comparisons were performed with the log-rank test. RESULTS: Primary
      unassisted patency rates following stent-graft placement at 4, 12, and 24 months
      (+/- standard error) were 64% +/- 14, 54% +/- 15, and 40% +/- 16, respectively.
      The rates for primary assisted patency were 78% +/- 12, 67% +/- 14, and 67% +/-
      14 and those for secondary patency were 91% +/- 9, 81% +/- 12, and 54% +/- 23. At
      12 months, primary unassisted patency with de novo stent-graft placement was 90%
      +/- 9, whereas that with stent-grafts placed during TIPS revision was 17% +/- 15
      (P = .005). At 12 months, the primary unassisted patency in patients with stent
      grafts confined to the parenchymal tract was 75% +/- 22, and that of patients
      with stent-grafts extending at least 1 cm into the portal vein was 40% +/- 17 (P
      = .21). CONCLUSION: In this small series, satisfactory long-term patency was
      observed among patients in whom Dacron-covered stent-grafts were placed during
      revision or de novo creation of TIPS. More favorable outcomes were observed when
      the stent-graft was placed during de novo TIPS creation and when the device was
      confined to the parenchymal tract.

PMID- 16000641
TI  - Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients
      with haematological malignancy on completion of cytotoxic chemotherapy.
AB  - BACKGROUND: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive
      patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is
      unknown. AIMS: To examine the occurrence of hepatitis B virus (HBV) reactivation
      after withdrawal of pre-emptive lamivudine. METHODS: Pre-emptive lamivudine was
      started one week before initiation of chemotherapy in 46 consecutive HBsAg
      positive patients and continued for the entire duration of chemotherapy. Pre
      emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after
      completion of chemotherapy. Patients were longitudinally followed up after
      withdrawal of pre-emptive lamivudine. RESULTS: Median time of follow up after
      withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. Eleven of the 46
      patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive
      lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (> or
      =10(4) copies/ml) compared with three of the 30 patients with low pre
      chemotherapy HBV DNA (<10(4) copies/ml) developed HBV reactivation (50.0% v
      10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also
      more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%),
      respectively; p = 0.041). A high pre-chemotherapy HBV DNA (> or =10(4) copies/ml)
      was the most important risk factor for HBV reactivation after withdrawal of pre
      emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13,
      (95% confidence interval 2.99-87.01; p = 0.001). CONCLUSIONS: HBV reactivation is
      more likely to occur in patients with high pre-chemotherapy HBV DNA after
      withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral
      therapy may be necessary in these patients after completion of chemotherapy in
      order to reduce post-chemotherapy HBV reactivation.

PMID- 16000642
TI  - Genetic basis for increased intestinal permeability in families with Crohn's
      disease: role of CARD15 3020insC mutation?
AB  - BACKGROUND AND AIMS: A genetically impaired intestinal barrier function has long
      been suspected to be a predisposing factor for Crohn's disease (CD). Recently,
      mutations of the capsase recruitment domain family, member 15 (CARD15) gene have
      been identified and associated with CD. We hypothesise that a CARD15 mutation may
      be associated with an impaired intestinal barrier. METHODS: We studied 128
      patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related
      household members (CD-NR), and 96 healthy controls. The three most common CARD15
      polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal
      permeability was determined by the lactulose/mannitol ratio. RESULTS: Intestinal
      permeability was significantly increased in CD and CD-R groups compared with CD
      NR and controls. Values above the normal range were seen in 44% of CD and 26% of
      CD-R but only in 6% of CD-NR, and in none of the controls. A household community
      with CD patients, representing a common environment, was not associated with
      increased intestinal permeability in family members. However, 40% of CD first
      degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R
      with combined 3020insC and R702W mutations had increased intestinal permeability
      compared with only 15% of wild-types, indicating a genetic influence on barrier
      function. R702W and G908R mutations were not associated with high permeability.
      CONCLUSIONS: In healthy first degree relatives, high mucosal permeability is
      associated with the presence of a CARD15 3020insC mutation. This indicates that
      genetic factors may be involved in impairment of intestinal barrier function in
      families with IBD.

PMID- 16000649
TI  - Quantification of intravenously administered contrast medium transit through the
      peripheral arteries: implications for CT angiography.
AB  - PURPOSE: To prospectively determine the range of aortopopliteal bolus transit
      times in patients with moderate-to-severe peripheral arterial occlusive disease
      (PAOD) as a guideline for developing injection strategies for computed
      tomographic (CT) angiography of peripheral arteries. MATERIALS AND METHODS: The
      study protocol was approved by the local ethics board, and informed consent was
      obtained. Twenty patients with PAOD referred for CT angiography of the lower
      extremities were categorized into two groups, Fontaine stage IIb (group 1) and
      stage III or IV (group 2), and demographic information was collected. In all
      patients, a 16-mL test bolus was injected intravenously, and single-level dynamic
      acquisitions were obtained at the level of the abdominal aorta. After injection
      of a second 16-mL test bolus, dynamic acquisitions were obtained at the level of
      the knee (popliteal arteries). Aortopopliteal bolus transit times were calculated
      by subtracting the time to peak enhancement in the popliteal arteries from that
      in the aorta. Aortopopliteal transit speeds also were derived. Transit times and
      speeds were compared graphically between clinical stage groups. The time required
      for the contrast medium to enhance the entire peripheral arterial tree in
      patients with PAOD was estimated by using linear extrapolation. RESULTS: Sixteen
      men and four women with a mean age of 69 years (range, 49-86 years) were
      included. Twelve patients were included in group 1, and eight patients, in group
      2. Aortopopliteal bolus transit times ranged from 4 to 24 seconds (median, 8
      seconds) in all subjects, which corresponded to bolus transit speeds of 177 and
      29 mm/sec, respectively. Wide overlap of transit times and transit speeds was
      observed between clinical stage groups. The estimated time needed for the bolus
      to enhance the entire peripheral arterial tree was 6-39 seconds. CONCLUSION:
      Aortopopliteal bolus transit times differ widely among patients and may be
      substantially delayed in all patients with PAOD. Empirical injection protocols
      should include an injection duration of 35 seconds or more, as well as an
      increased scanning delay, with table speeds of more than 30 mm/sec.

PMID- 16000650
TI  - Divergence time of porcine reproductive and respiratory syndrome virus subtypes.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) recently emerged in
      domestic pigs of Western Europe and North America. Although time of emergence was
      identical on the two continents, genetic composition was markedly different with
      a clear geographical subtype structure, indicating that subtypes diverged in
      separate reservoirs prior to emergence. Genetic analyses have shown that the most
      recent common ancestor (MRCA) of Western European isolates existed around 1980
      and that these originate from Eastern European pigs. These findings are
      challenged by a study of Hanada et al. who place the MRCA of all PRRSV isolates
      around 1980 and find that no significant subtype divergence occurred before
      emergence. Here, I discuss problems of information content, methodology, and
      biological plausibility associated with this study. Using alternative
      methodology, I reanalyze the existing data and conclude that the MRCA of all
      PRRSV isolates existed around 1880, 100 years before the date estimated by Hanada
      et al.

PMID- 16000651
TI  - BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the
      marginal zone plays a role in the development of cortical organization.
AB  - The present study utilizes nestin-BDNF transgenic mice, which offer a model for
      early increased brain-derived neurotrophic factor (BDNF) signalling, to examine
      the role of BDNF in the development of cortical architecture. Our results
      demonstrate that the premature and homogeneous expression of BDNF, while
      preserving tangential migration from the ganglionic eminence to the cortex,
      impairs the final radial migration of GABAergic neurons, as well as their
      integration in the appropriate cortical layers. Moreover, Cajal-Retzius (CR)
      cells and GABAergic neurons segregate in the cortical marginal zone (MZ) in
      response to BDNF signalling, leading to an alternating pattern and a columnar
      cortical organization, within which the migration of different neuronal
      populations is specifically affected. These results suggest that both CR and
      GABAergic neurons play a role in directing the radial migration of late-generated
      cortical neurons, and that the spatial distribution of these cells in the MZ is
      critical for the development of correct cortical organization. In addition,
      reelin secreted by CR cells in the MZ is not sufficient to direct the migration
      of late-born neurons to the upper cortical layers, which most likely requires the
      presence of reelin-secreting interneurons in layers V-VI. We propose that in
      addition to modulating reelin expression, BDNF regulates the patched distribution
      of CR and GABAergic neurons in the MZ, and that this spatial distribution is
      involved in the formation of anatomical and/or functional columns and convoluted
      structures.

PMID- 16000652
TI  - Neural evidence for dissociable components of task-switching.
AB  - The ability to retrieve and flexibly switch between task rules is seen as an
      important component of cognitive control. It is often assumed that lateral
      prefrontal cortex (latPFC) is important for switching between rules. However,
      activation associated with rule-switching is less reliably observed in latPFC
      than in medial PFC (specifically, pre-supplementary motor area). In this study,
      we tested the hypothesis that medial PFC is important for reconfiguration of task
      sets, whereas latPFC is important for retrieving, maintaining and implementing
      relevant rules (i.e. rule representation). Twenty young adults participated in a
      functional magnetic resonance imaging study in which they determined the correct
      response to a target stimulus on the basis of an instructional cue. For bivalent
      targets, the appropriate response depended on the currently relevant rule. In
      contrast, univalent targets were always associated with the same response. Brain
      regions of interest were characterized according to their responsiveness to
      bivalent and univalent targets, on both rule-switch and rule-repetition trials.
      The data support the hypothesis that rule representation and task-set
      reconfiguration are separable cognitive processes, associated with dissociable
      neural activation in latPFC and medial PFC, respectively. Activation profiles of
      posterior parietal cortex, basal ganglia and rostrolateral PFC are also examined
      and discussed.

PMID- 16000653
TI  - Cardiac events in New Jersey after the September 11, 2001, terrorist attack.
AB  - The higher stress associated with the World Trade Center (WTC) attacks on
      September 11, 2001, may have resulted in more cardiac events particularly in
      those living in close proximity. Our goal was to determine if there was an
      increase in cardiac events in a subset of emergency departments (EDs) within a 50
      mi radius of the WTC. We performed a retrospective analysis of consecutive
      patients seen by ED physicians in 16 EDs for the 60 days before and after
      September 11 in 2000-2002. We determined the number of patients admitted to an
      inpatient bed with a primary or secondary diagnosis of acute myocardial
      infarction (MI) or tachyarrhythmia. In each year, we compared patient visits for
      the 60 days before and after September 11 using the chi-square statistic. For the
      360 days during the 3 years, there were 571,079 patient visits in the database of
      which 110,766 (19.4%) were admitted. Comparing the 60 days before and after
      September 11, 2001, we found a statistically significant increase in patients
      with MIs (79 patients before versus 118 patients after, P =.01), representing an
      increase of 49%. There were no statistically significant differences for MIs in
      2000 and 2002 and in tachyarrhythmias for all three years. For the 60-day period
      after September 11, 2001, we found a statistically significant increase in the
      number of patients presenting with acute MI but no increase in patients admitted
      with tachyarrhythmias.

PMID- 16000654
TI  - Health care workers' ability and willingness to report to duty during
      catastrophic disasters.
AB  - Catastrophic disasters create surge capacity needs for health care systems. This
      is especially true in the urban setting because the high population density and
      reliance on complex urban infrastructures (e.g., mass transit systems and high
      rise buildings) could adversely affect the ability to meet surge capacity needs.
      To better understand responsiveness in this setting, we conducted a survey of
      health care workers (HCWs) (N =6,428) from 47 health care facilities in New York
      City and the surrounding metropolitan region to determine their ability and
      willingness to report to work during various catastrophic events. A range of
      facility types and sizes were represented in the sample. Results indicate that
      HCWs were most able to report to work for a mass casualty incident (MCI) (83%),
      environmental disaster (81%), and chemical event (71%) and least able to report
      during a smallpox epidemic (69%), radiological event (64%), sudden acute
      respiratory distress syndrome (SARS) outbreak (64%), or severe snow storm (49%).
      In terms of willingness, HCWs were most willing to report during a snow storm
      (80%), MCI (86%), and environmental disaster (84%) and least willing during a
      SARS outbreak (48%), radiological event (57%), smallpox epidemic (61%), and
      chemical event (68%). Barriers to ability included transportation problems, child
      care, eldercare, and pet care obligations. Barriers to willingness included fear
      and concern for family and self and personal health problems. The findings were
      consistent for all types of facilities. Importantly, many of the barriers
      identified are amenable to interventions.

PMID- 16000655
TI  - Deteriorating outcomes after meniscal repair using the Meniscus Arrow in knees
      undergoing concurrent anterior cruciate ligament reconstruction: increased
      failure rate with long-term follow-up.
AB  - BACKGROUND: An increased awareness of the degenerative changes that occur in the
      knee after meniscectomy has led to efforts to salvage the injured meniscus.
      Numerous devices have been developed in an effort to provide the dual benefits of
      a durable meniscal repair and minimal invasiveness. HYPOTHESIS: The Meniscus
      Arrow is comparable to conventional inside-out suture repair in accomplishing
      long-term healing of meniscal tears. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: This study is an extended follow-up of an original series
      of 32 patients with outcomes analysis. All patients underwent meniscal repair
      with exclusive use of the arrow. All repairs were performed in the context of a
      concomitant anterior cruciate ligament reconstruction. Follow-up assessment
      included physical examination, arthrometry, the International Knee Documentation
      Committee instrument, and the Knee Disorders Subjective History visual analog
      scale. Intermediate follow-up at a mean of 2.3 years yielded a success rate of
      90.6%. The mean follow-up in the present study has been extended to 6.6 years.
      RESULTS: The extended follow-up analysis revealed a substantial attrition in the
      success rate of this series of patients undergoing meniscal repair with the
      arrow. A 90.6% success rate at a mean follow-up of 2.3 years deteriorated to
      71.4% at 6.6 years. CONCLUSION: This study provides the longest follow-up in the
      literature of any of the all-inside meniscal repair implants. The Meniscus Arrow
      demonstrated long-term meniscal healing rates inferior to those found in the
      literature for inside-out suture repair techniques.

PMID- 16000656
TI  - The effect of long-distance bicycling on ulnar and median nerves: an
      electrophysiologic evaluation of cyclist palsy.
AB  - BACKGROUND: Distal ulnar neuropathies have been identified in cyclists because of
      prolonged grip pressures on handlebars. The so-called cyclist palsy has been
      postulated to be an entrapment neuropathy of the ulnar nerve in the Guyon canal
      of the wrist. Previous studies utilizing nerve conduction studies have typically
      been either case reports or small case series. HYPOTHESIS: Electrophysiologic
      changes will be present in the ulnar and median nerves after a long-distance
      multiday cycling event. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: A total of 28 adult hands from 14 subjects underwent median and ulnar
      motor and sensory nerve conductions, which were performed on both hands before
      and after a 6-day, 420-mile bike tour. A ride questionnaire was also administered
      after the ride, evaluating the experience level of the cyclist, equipment issues,
      hand position, and symptoms during the ride. RESULTS: Distal motor latencies of
      the deep branch of the ulnar nerve to the first dorsal interosseous were
      significantly prolonged after the long-distance cycling event. The median motor
      and sensory studies as well as the ulnar sensory and motor studies of the
      abductor digiti minimi did not change significantly. Electrophysiologic and
      symptomatic worsening of carpal tunnel syndrome was observed in 3 hands, with the
      onset of carpal tunnel syndrome in 1 hand after the ride. CONCLUSION: Long
      distance cycling may promote physiologic changes in the deep branch of the ulnar
      nerve and exacerbate symptoms of carpal tunnel syndrome.

PMID- 16000657
TI  - Epidemiology of lacrosse injuries in high school-aged girls and boys: a 3-year
      prospective study.
AB  - OBJECTIVE: To report the types, mechanisms, and circumstances of lacrosse
      injuries incurred by high school-aged girls and boys during organized
      interscholastic and summer camp games. STUDY DESIGN: Descriptive epidemiology
      study. METHODS: For 3 years, the authors gathered data on girls' and boys'
      lacrosse injuries for 359 040 high school and 28 318 summer camp athletic
      exposures using a lacrosse-specific computerized injury surveillance system. The
      most prevalent injuries were organized into multifactorial injury scenarios.
      RESULTS: In high school play, the injury rate for adolescent boys (2.89 per 1000
      athletic exposures) was slightly higher than that for girls (2.54 per 1000
      athletic exposures) (incidence rate ratio = 1.14; 95% confidence interval, 1.00
      1.30). The most prevalent injuries for adolescent girls and boys were knee and
      ankle sprains resulting from noncontact mechanisms. Male players had
      significantly higher rates of shoulder, neck, trunk, and back injuries and higher
      game-to-practice injury ratios. In addition, they had higher rates of concussive
      events from player-to-player contact. Female players had higher rates of overall
      head injuries, many involving contusions and abrasions from stick and ball
      contact. CONCLUSIONS: The overall injury rates for boys' and girls' high school
      lacrosse were significantly lower than those for collegiate play. Significant
      differences existed between adolescent boys and girls with respect to injury
      mechanisms, body parts injured, and player and team activity at the time of
      injury.

PMID- 16000658
TI  - Peroneus longus muscle activation pattern during gait cycle in athletes affected
      by functional ankle instability: a surface electromyographic study.
AB  - BACKGROUND: Functional ankle instability is a clinical syndrome that may develop
      after acute lateral ankle sprain. Although several causes of this functional
      instability have been suggested, it is still unclear what the activation pattern
      of the peroneus longus muscle is in patients with functional ankle instability.
      HYPOTHESIS: Peroneus longus activation patterns differ in the injured side and
      the uninjured side in subjects with functional ankle instability. STUDY DESIGN:
      Descriptive laboratory study. METHODS: The authors examined 14 subjects with
      functional ankle instability by using surface electromyography during walking.
      Activation time of the peroneus longus muscle was expressed as a percentage of
      the stance phase of the gait cycle. RESULTS: A statistically significant decrease
      in peroneus longus muscle activity was found in the injured side compared with
      the uninjured side (22.8% +/- 4.25% vs 37.6% +/- 3.5%, respectively).
      CONCLUSIONS: Results obtained in this study show a change in peroneus longus
      muscle activation time after injury. Independent of the origin of this change,
      which could only be surmised, the decrease in peroneus longus muscle activity may
      result in reduced protection against lateral sprains. CLINICAL RELEVANCE: The
      assessment of peroneus longus activation pattern during gait is useful to design
      an appropriate rehabilitation program in athletes suffering from functional ankle
      instability.

PMID- 16000659
TI  - Functional outcome of knee articular cartilage repair in adolescent athletes.
AB  - BACKGROUND: Limited information exists about the treatment of full-thickness
      articular cartilage lesions of the knee in adolescent athletes. PURPOSE: To
      evaluate the functional outcome and athletic activity after articular cartilage
      repair in the knees of adolescent athletes. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Twenty adolescent athletes with full-thickness articular
      cartilage lesions of the knee were treated with autologous chondrocyte
      transplantation. Functional outcome was evaluated by subjective patient outcome
      rating, knee activity scores, and level of athletic participation. RESULTS: At a
      mean of 47 months after autologous chondrocyte transplantation, 96% of
      adolescents reported good or excellent results with significant increases in
      postoperative Tegner activity scores and Lysholm scores. Ninety-six percent
      returned to high-impact sports and 60% to an athletic level equal or higher than
      that before knee injury. Return to preinjury sports correlated with shorter
      preoperative symptoms and a lower number of prior operations. All adolescents
      with preoperative symptoms < or =12 months returned to preinjury-level athletics,
      compared to 33% with preoperative intervals longer than 12 months. CONCLUSION:
      Treatment of full-thickness articular injuries of the knee in adolescent athletes
      with autologous chondrocyte transplantation yields a high rate of functional
      success at a mean follow-up of 47 months. The rate of return to demanding
      athletic activities is higher in cases in which the preoperative duration of
      symptoms is 12 months or less.

PMID- 16000660
TI  - Popliteomeniscal fascicle tears causing symptomatic lateral compartment knee
      pain: diagnosis by the figure-4 test and treatment by open repair.
AB  - BACKGROUND: Injuries to the popliteomeniscal fascicles of the lateral meniscus
      are difficult to identify from physical examination and magnetic resonance
      imaging scans. To our knowledge, there have been no described physical
      examination techniques to identify symptomatic isolated popliteomeniscal fascicle
      tears. The popliteomeniscal fascicles have been demonstrated to be important for
      lateral meniscus stability, and it has been reported that tears can lead to
      painful symptoms. HYPOTHESIS: Popliteomeniscal fascicle tears cause symptomatic
      lateral compartment knee pain and can be diagnosed by physical examination.
      Surgical repair can improve patient function. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Six patients with isolated tears of the popliteomeniscal
      fascicles, which caused lateral joint line knee pain, were identified by positive
      figure-4 test results. RESULTS: All patients were found to have replication of
      their symptoms while placing the affected knee in the figure-4 position and were
      found to have lateral meniscal hypermobility due to tears of the popliteomeniscal
      fascicles on arthroscopic examination. All patients had an open repair of the
      popliteomeniscal fascicles of the lateral meniscus with complete resolution of
      their symptoms at a mean follow-up of 3.8 years postoperatively. CONCLUSIONS: The
      figure-4 test was found to be useful in identifying the source of lateral
      compartment knee pain due to popliteomeniscal fascicle tears. Open repair of
      isolated popliteomeniscal fascicle tears was also found to be effective in
      resolving lateral compartment knee pain due to popliteomeniscal fascicle tears.

PMID- 16000661
TI  - Score-celebration injuries among soccer players: a report of 9 cases.
AB  - BACKGROUND: Professional and amateur soccer players often perform dramatic on
      field feats of celebration after scoring a goal. Injuries may occur during these
      activities. PURPOSE: With the aim of preventing such "score-celebration injuries"
      in the future, the authors examine these events in professional soccer players
      and discuss potential avenues for prevention. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Over the course of 2 seasons (1996-1998), 152 soccer
      players were evaluated at an orthopaedic clinic for injuries incurred during
      matches. Nine players (6%) had injured themselves while celebrating after scoring
      goals in a match. The type of celebration, injury type, treatment, and mean
      duration of recovery were noted. RESULTS: Seven of the 9 patients were male
      professional soccer players with ages ranging between 17 and 29 years (mean age,
      24 years). The injuries occurred when the playing ground was natural turf in 8
      cases; most injuries occurred in the second half of the game. The types of
      celebration maneuvers were sliding (prone or supine) and sliding while kneeling
      in 5 cases, piling up on jubilant teammates in 3 cases, and being tackled while
      racing away in 1 case. Injuries included ankle, clavicle, and rib fractures;
      medial collateral ligament sprain; low back strain; hamstring and adductor muscle
      strain; quadriceps muscle sprain; and coccyx contusion. The mean duration for
      recovery was 6.2 weeks. Rival team players were usually not responsible for such
      trauma. CONCLUSION: Exaggerated celebrations after making a goal, such as
      sliding, piling up, and tackling a teammate when racing away, can result in
      serious injury. In addition to general measures for preventing soccer injuries,
      coaches and team physicians should teach self-control and behavior modification
      to minimize the risk of such injuries. More restrictive rules, which penalize
      such behavior, may assist in the prevention of score-celebration injuries.

PMID- 16000662
TI  - Tendon-to-bone pressure distributions at a repaired rotator cuff footprint using
      transosseous suture and suture anchor fixation techniques.
AB  - BACKGROUND: Interface contact pressure between the tendon and bone has been shown
      to influence healing. This study evaluates the interface pressure of the rotator
      cuff tendon to the greater tuberosity for different rotator cuff repair
      techniques. HYPOTHESIS: The transosseous tunnel rotator cuff repair technique
      provides larger pressure distributions over a defined insertion footprint than do
      suture anchor techniques. STUDY DESIGN: Controlled laboratory study. METHODS:
      Simulated rotator cuff tears over a 1 x 2-cm infraspinatus insertion footprint
      were created in 25 bovine shoulders. A transosseous tunnel simple suture
      technique (n = 8), suture anchor simple technique (n = 9), and suture anchor
      mattress technique (n = 8) were used for repair. Pressurized contact areas and
      mean pressures of the repaired tendon against the tuberosity were determined
      using pressure-sensitive film placed between the tendon and the tuberosity.
      RESULTS: The mean contact area between the tendon and tuberosity insertion
      footprint was significantly greater for the transosseous technique (67.7 +/- 5.8
      mm(2)) compared with the suture anchor simple (34.1 +/- 9.4 mm(2)) and suture
      anchor mattress (26.0 +/- 5.3 mm(2)) techniques (P < .05). The mean interface
      pressure exerted over the footprint by the tendon was also greater for the
      transosseous technique (0.32 +/- 0.05 MPa) compared with the suture anchor simple
      (0.26 +/- 0.04 MPa) and suture anchor mattress (0.24 +/- 0.02 MPa) techniques (P
      < .05). CONCLUSION: The transosseous tunnel rotator cuff repair technique creates
      significantly more contact and greater overall pressure distribution over a
      defined footprint when compared with suture anchor techniques. CLINICAL
      RELEVANCE: Stronger and faster rotator cuff healing may be expected when
      beneficial pressure distributions exist between the repaired rotator cuff and its
      insertion footprint. Tendon-to-tuberosity pressure and contact characteristics
      should be considered in the development of improved open and arthroscopic rotator
      cuff repair techniques.

PMID- 16000663
TI  - Application of tissue engineering techniques for rotator cuff regeneration using
      a chitosan-based hyaluronan hybrid fiber scaffold.
AB  - BACKGROUND: The current surgical procedures for irreparable rotator cuff tears
      have considerable limitations. Tissue engineering techniques using novel scaffold
      materials offer potential alternatives for managing these conditions. HYPOTHESIS:
      A chitosan-based hyaluronan hybrid scaffold could enhance type I collagen
      products with seeded fibroblasts and thereby increase the mechanical strength of
      regenerated tendon in vivo. STUDY DESIGN: Controlled laboratory study. METHODS:
      The scaffolds were created from chitosan-based hyaluronan hybrid polymer fibers.
      Forty-eight rabbit infraspinatus tendons and their humeral insertions were
      removed to create defects. Each defect was covered with a fibroblast-seeded
      scaffold (n = 16) or a non-fibroblast-seeded scaffold (n = 16). In the other 16
      shoulders, the rotator cuff defect was left free as the control. At 4 and 12
      weeks after surgery, the engineered tendons were assessed by histological,
      immunohistochemical (n = 2), and biomechanical (n = 6) analyses. RESULTS: Type I
      collagen was only seen in the fibroblast-seeded scaffold and increased in the
      regenerated tissue. The tensile strength and tangent modulus in the fibroblast
      seeded scaffold were significantly improved from 4 to 12 weeks postoperatively.
      The fibroblast-seeded scaffold had a significantly greater tangent modulus than
      did the non-fibroblast-seeded scaffold and the control at 12 weeks. CONCLUSION:
      This scaffold material enhanced the production of type I collagen and led to
      improved mechanical strength in the regenerated tissues of the rotator cuff in
      vivo. CLINICAL RELEVANCE: Rotator cuff regeneration is feasible using this tissue
      engineering technique.

PMID- 16000664
TI  - The Kim test: a novel test for posteroinferior labral lesion of the shoulder--a
      comparison to the jerk test.
AB  - BACKGROUND: Detection of a posteroinferior labral lesion by physical examination
      is often difficult. PURPOSE: To introduce a novel diagnostic test for detecting a
      posteroinferior labral lesion of the shoulder. HYPOTHESIS: The Kim test can
      detect a posteroinferior labral lesion of the shoulder. STUDY DESIGN: Cohort
      study (diagnosis); Level of evidence, 1. METHODS: In 172 painful shoulders, the
      Kim test was compared with the jerk test and was verified by arthroscopic
      examination. A sudden onset of posterior shoulder pain and click with or without
      clunk indicated a positive test result. RESULTS: Thirty-three shoulders had a
      positive Kim test result, in which 24 had a posteroinferior labral lesion and 9
      had a normal posteroinferior labrum. Of 139 shoulders with a negative Kim test
      result, 6 had a posteroinferior labral tear and 133 had a normal posteroinferior
      labrum. The sensitivity of the Kim test was 80%, specificity was 94%, positive
      predictive value was 0.73, and negative predictive value was 0.96. The
      interexaminer reliability between 2 examiners was 0.91. The accuracy of the jerk
      test in detecting a posteroinferior labral lesion was the following: sensitivity,
      73%; specificity, 98%; positive predictive value, 0.88; and negative predictive
      value, 0.95. The location of the posterior labral lesion was predominantly
      posterior in 19 shoulders and predominantly inferior in 11 shoulders. The Kim
      test was more sensitive in detecting a predominantly inferior labral lesion,
      whereas the jerk test was more sensitive in detecting a predominantly posterior
      labral lesion. The sensitivity in detecting a posteroinferior labral lesion
      increased to 97% when the 2 tests were combined. CONCLUSION: The Kim test is a
      reliable diagnostic test for detection of a posteroinferior labral lesion.

PMID- 16000665
TI  - Long-term evaluation of the Roux-Elmslie-Trillat procedure for patellar
      instability: a 26-year follow-up.
AB  - BACKGROUND: Few published articles exist reporting the long-term evaluation of
      the Roux-Elmslie-Trillat procedure. PURPOSE: To assess the long-term effect of
      the Roux-Elmslie-Trillat procedure in preventing recurrent subluxation and
      dislocation of the patella. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Eighteen patients who underwent the Roux-Elmslie-Trillat procedure for
      dislocation or subluxation of the patella were identified from a group previously
      evaluated at a mean follow-up of 3 years. The prevalence of recurrent subluxation
      or dislocation at a mean follow-up of 26 years was compared with the prevalence
      reported at the mean follow-up of 3 years. Although not the focus of this study,
      Cox functional scores were obtained from the smaller group and compared with the
      results at the 3-year follow-up. RESULTS: Seven percent (95% confidence interval,
      0.00-0.32) of the patients had recurrent subluxation at 26 years compared with 7%
      (95% confidence interval, 0.03-0.13) of the study population reported at 3 years
      (P = 1.00). Fifty-four percent (95% confidence interval, 0.27-0.79) rated their
      affected knee as good or excellent at 26 years compared with 73% (95% confidence
      interval, 0.64-0.81) of the larger study population reported at 3 years (P =
      .14). CONCLUSION: The prevalence of recurrent subluxation and dislocation in
      patients with patellofemoral malalignment who underwent the Roux-Elmslie-Trillat
      procedure for dislocation or subluxation of the patella is similar at 3 and 26
      years after the procedure. The long-term functional status of the affected knee
      in patients who underwent the Roux-Elmslie-Trillat procedure declined.

PMID- 16000666
TI  - Endoscopic reconstruction of the anterior cruciate ligament using bone-patellar
      tendon-bone grafts fixed with bioabsorbable or metal interference screws: a
      prospective randomized study of the clinical outcome.
AB  - BACKGROUND: During the past decade, bioabsorbable interference screws have become
      increasingly popular in endoscopic reconstructions of the anterior cruciate
      ligament. With these screws, there is no need for a second operation for removal
      and no complicating factor if later revision surgery is necessary. Several
      pullout studies have found similar results between metal and bioabsorbable
      interference screws; however, few studies have investigated the clinical outcome.
      HYPOTHESIS: There is no difference in the clinical outcome of bioabsorbable
      interference screws compared with metal screws. STUDY DESIGN: Randomized
      controlled clinical trial; Level of evidence, 1. METHODS: Forty-one patients were
      randomized for the use of either metal interference screws (20 patients) or
      bioabsorbable poly-l-lactic acid screws (21 patients). The patients were followed
      with clinical examinations at 6, 12, and 24 weeks and at 1 and 2 years
      postoperatively. RESULTS: Subjective knee function was better in the patients in
      the metal screw group; they had less pain at rest, a higher Tegner score, a
      higher Lysholm score, and better subjective knee function at 2 years compared to
      the bioabsorbable screw group. However, there was no difference in stability
      between the groups. CONCLUSION AND CLINICAL RELEVANCE: Because of the inferior
      results in the bioabsorbable screw group in our study, and until larger studies
      show otherwise, we do not find the advantages of using bioabsorbable screws
      sufficient to warrant the routine use of poly-L-lactic acid screws in anterior
      cruciate ligament reconstructions.

PMID- 16000667
TI  - Ankle joint proprioception and postural control in basketball players with
      bilateral ankle sprains.
AB  - BACKGROUND: Deficiencies in ankle proprioception and standing balance in
      basketball players with multiple ankle sprains have been reported in separate
      studies. However, the question of how ankle proprioceptive inputs and postural
      control in stance are related is still unclear. HYPOTHESIS: Ankle repositioning
      errors and the amount of postural sway in stance are increased in basketball
      players with multiple ankle sprains. STUDY DESIGN: Controlled laboratory study.
      METHODS: Twenty healthy male basketball players and 19 male basketball players
      who had suffered bilateral ankle sprains within the past 2 years were examined.
      Both groups were similar in age. Passive ankle joint repositioning errors at 5
      degrees of plantar flexion were used to test for ankle joint proprioception. The
      Sensory Organization Test was applied with dynamic posturography to assess
      postural sway angle under 6 sensory conditions. RESULTS: A significant increase
      in ankle repositioning errors was demonstrated in basketball players with
      bilateral ankle sprains (P < .05). The mean errors in the right and left ankles
      were increased from 1.0 degrees (standard deviation, 0.4 degrees ) and 0.8
      degrees (standard deviation, 0.2 degrees ), respectively, in the healthy players
      to 1.4 degrees (standard deviation, 0.7 degrees ) and 1.1 degrees (standard
      deviation, 0.5 degrees ) in the injured group. A significant increase in the
      amount of postural sway in the injured subjects was also found in conditions 1,
      2, and 5 of the Sensory Organization Test (P < .05). Furthermore, there were
      positive associations between averaged errors in repositioning both ankles and
      postural sway angles in conditions 1, 2, and 3 of the Sensory Organization Test
      (r = 0.39-0.54, P < .05). CONCLUSIONS: Ankle repositioning errors and postural
      sway in stance increased in basketball players with multiple ankle sprains. A
      positive relationship was found between these 2 variables. CLINICAL RELEVANCE:
      Such findings highlight the need for the rehabilitation of patients with multiple
      ankle sprains to include proprioceptive and balance training.

PMID- 16000668
TI  - The "ligamentization" process in human anterior cruciate ligament reconstruction
      with autogenous patellar and hamstring tendons: a biochemical study.
AB  - BACKGROUND: There is little information documenting whether the phenomenon of
      "ligamentization," as proposed by Amiel, occurs in the human anterior cruciate
      ligament after clinically effective reconstruction. To clarify this point, we
      analyzed biochemical differences between the native anterior cruciate ligament;
      the patellar, semitendinosus, and gracilis tendons; and anterior cruciate
      ligaments reconstructed with autografts. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: Fifty patients who underwent arthroscopically assisted
      anterior cruciate ligament reconstruction using either semitendinosus and
      gracilis tendon or bone-patellar tendon-bone autografts were selected for the
      study. Samples of grafted tissue were collected during arthroscopy and
      quantitatively analyzed for collagen content and the amount of reducible and
      nonreducible crosslinks at 4 to 6 postoperative months in patients with
      semitendinosus and gracilis tendon grafts and at 11 to 13 months in all patients
      with semitendinosus and gracilis tendon or bone-patellar tendon-bone grafts.
      RESULTS: The total collagen content and nonreducible/reducible crosslink ratios
      increased significantly during the postoperative period (P < .05). The
      dihydroxylysinonorleucine/hydroxylysinonorleucine ratio was 3.11 +/- 0.56 in the
      native anterior cruciate ligament, 1.21 +/- 0.47 in the patellar tendon, and 3.59
      +/- 1.58 in the anterior cruciate ligaments reconstructed with bone-patellar
      tendon-bone autografts 1 year after surgery. The
      dihydroxylysinonorleucine/hydroxylysinonorleucine ratio in both semitendinosus
      and gracilis tendons was less than 1.0. However, in anterior cruciate ligaments
      reconstructed with semitendinosus and gracilis tendon autografts, it was 2.34 +/-
      0.98 at 4 to 6 months and 3.43 +/- 1.61 at 11 to 13 months after the operation.
      CONCLUSIONS: After anterior cruciate ligament reconstruction with autografts,
      biochemical characteristics of the graft resembled those of the native anterior
      cruciate ligament. These findings suggest that, regarding the amount of collagen
      crosslinks and their architecture, the phenomenon of ligamentization occurs in
      the successfully reconstructed human anterior cruciate ligament within 1 year
      after operation.

PMID- 16000669
TI  - Football equipment design affects face mask removal efficiency.
AB  - BACKGROUND: Researchers have investigated the performance of face mask removal
      tools for spine injury management in football but not the effects of football
      equipment design. HYPOTHESES: Various styles or designs of football helmet
      equipment (helmets, face masks, loop straps) affect face mask removal efficiency.
      A cordless screwdriver performs more efficiently than do cutting tools. STUDY
      DESIGN: Controlled laboratory study. METHODS: Nineteen certified athletic
      trainers were randomly assigned to group 1 (cordless screwdriver and the FM
      Extractor) or group 2 (cordless screwdriver and the Trainer's Angel). Subjects
      randomly performed face mask removal for 6 conditions composed of helmet (3),
      face mask (3), and loop strap (5) combinations. Time, head movement, perceived
      difficulty, and success rates were measured. RESULTS: Multiple significant
      differences were found in time, movement, and perceived difficulty between the 6
      helmet equipment conditions. The Shockblocker loop strap was consistently
      superior in all variables regardless of the tool used or the helmet it was
      attached to. The cordless screwdriver created less movement (mean range from any
      one plane, 2.8 degrees -13.3 degrees ), was faster (mean range, 42.1-68.8
      seconds), and was less difficult (mean rating of perceived exertion range, 1.4
      2.9) compared to cutting tools (ranges, 4.4 degrees -18.4 degrees in any one
      plane, 71-174 seconds, rating of perceived exertion, 2.8-7.7). Trial failure was
      more common with cutting tools than with the screwdriver. CONCLUSION: Differences
      in football helmet equipment affect face mask removal. The cordless screwdriver
      is more efficient than the FM Extractor and Trainer's Angel. CLINICAL RELEVANCE:
      Professionals responsible for the care of football athletes must be knowledgeable
      in the types of equipment used and the best option available for effective airway
      access.

PMID- 16000670
TI  - Clinical comparison of the Tutoplast allograft and autologous patellar tendon
      (bone-patellar tendon-bone) for the reconstruction of the anterior cruciate
      ligament: 2- and 6-year results.
AB  - BACKGROUND: The use of an allograft as a suitable transplant is still open to
      debate, in terms of donor morbidity, implantation reaction, and long-term
      results, as well as the risk of disease transmission. HYPOTHESIS: The clinical
      results 2 and 6 years after implantation of a bone-patellar tendon-bone allograft
      (Tutoplast) and bone-patellar tendon-bone autograft show no significant
      difference in relation to stability, function, and rate of rupture. STUDY DESIGN:
      Cohort study; Level of evidence, 2. METHOD: Between 1995 and 1998, 268 patients
      with anterior cruciate ligament ruptures were surgically treated: 132 patients
      received a bone-patellar tendon-bone allograft implantation and 136 patients a
      bone-patellar tendon-bone autograft. The results were evaluated using the
      International Knee Documentation Committee, Noyes, and Lysholm scores. RESULTS:
      There were 201 patients assessable after 2 years and 186 patients after 6 years.
      Ruptures of the implants in the allograft group occurred in 20 patients (20.6%)
      within 2 years and in 38 patients (44.7%) after 6 years. In the autograft group,
      transplants ruptured in 5 patients (4.8%) after 2 years and in 6 patients (5.9%)
      after 6 years. CONCLUSION: Based on the data, it would appear that the regular
      use of bone-patellar tendon-bone allografts, particularly for physically active
      patients, is unsuitable.

PMID- 16000671
TI  - Psychiatric complications of anabolic steroid abuse.
AB  - The authors review the literature from human and animal studies on the
      neurochemical and pathological psychiatric effects of supraphysiological doses of
      anabolic-androgenic steroids (AAS) and discuss the AAS use and abuse patterns,
      additional drug use patterns, and personality and behavioral characteristics of
      AAS abusers.

PMID- 16000672
TI  - Acute akathisia associated with quetiapine use.
AB  - Because of their better side-effect profile, atypical antipsychotic agents have
      replaced conventional antipsychotic agents as the first-line treatment for
      schizophrenia. Although atypical agents are less likely to be associated with
      extrapyramidal symptoms, such symptoms sometimes do occur in patients treated
      with atypical agents. The authors report the cases of two patients who developed
      akathisia after treatment with quetiapine for insomnia, consider previously
      reported cases of akathisia induced by atypical antipsychotic agents, discuss
      other medications that can induce similar symptoms, discuss treatments for
      akathisia, and examine issues in the use of quetiapine as a soporific agent.

PMID- 16000673
TI  - Association between psychoactive medications and delirium in hospitalized
      patients: a critical review.
AB  - Psychoactive medications are often reported as delirium risk factors in
      hospitalized patients, and delirium induced by medication is potentially
      avoidable. The authors critically reviewed the evidence for a role of medications
      in delirium etiology. Only a few positive associations were noted. Use of
      psychoactive medications, considered together as a single variable, and use of
      opioids increased the risk of delirium. Data were scarce and sometimes
      conflicting, and methodological limitations were often present. The suspected
      association between psychoactive drugs and delirium cannot be unambiguously
      confirmed with current epidemiological evidence. The interpretation of these
      results must take into account the limitations of published studies, which should
      be addressed in future research.

PMID- 16000675
TI  - Headache attributed to psychiatric disorder: a case series.
AB  - The association between psychiatric illness and headache is widely recognized.
      However, cases in which psychiatric disorders are the principal cause of headache
      are believed to be rare. "Headache attributed to psychiatric disorder" is a new
      category of secondary headache in the 2004 revision of the International
      Classification of Headache Disorders. The authors describe six patients in whom a
      psychiatric disorder is the most plausible cause of headache; most meet the new
      criteria or candidate criteria for headache attributed to a psychiatric disorder.
      The revised headache classification system appropriately recognizes headaches
      attributed to psychiatric disorder as a form of secondary headache.

PMID- 16000674
TI  - Demographic characteristics, phenomenology, comorbidity, and family history in
      200 individuals with body dysmorphic disorder.
AB  - The authors examined characteristics of body dysmorphic disorder in the largest
      sample for which a wide range of clinical features has been reported. The authors
      also compared psychiatrically treated and untreated subjects. Body dysmorphic
      disorder usually began during adolescence, involved numerous body areas and
      behaviors, and was characterized by poor insight, high comorbidity rates, and
      high rates of functional impairment, suicidal ideation, and suicide attempts.
      There were far more similarities than differences between the currently treated
      and untreated subjects, although the treated subjects displayed better insight
      and had more comorbidity.

PMID- 16000676
TI  - Fluoxetine for vestibular dysfunction and anxiety: a prospective pilot study.
AB  - Anxiety states and disorders amplify the symptoms and impairment associated with
      vestibular dysfunction. Five patients with inner ear vestibular dysfunction and
      anxiety were prospectively treated with fluoxetine, 20-60 mg/day, and received an
      extensive battery of assessments at baseline and after 12 weeks of treatment.
      Fluoxetine led to significant or near significant reductions in anxiety measures
      and in impairment due to dizziness; improvements in clinical balance function and
      vestibular function were less clear. The data add to the literature suggesting a
      role for selective serotonin reuptake inhibitors in the treatment of dizziness
      and anxiety.

PMID- 16000677
TI  - Does somatosensory amplification decrease with antidepressant treatment?
AB  - Somatosensory amplification refers to a tendency to experience somatic and
      visceral sensations as unusually intense, noxious, and disturbing. The authors
      wanted to determine whether somatosensory amplification is a stable construct or
      whether it might change with antidepressant therapy. Fifteen patients with
      fibromyalgia and 17 patients with major depressive disorder received
      antidepressant treatment and were assessed after 6 and 12 weeks of treatment.
      Amplification scores responded to antidepressant treatment in patients with major
      depression but not in patients with fibromyalgia, despite a decrease in the
      levels of depression in both groups. When change in depression and anxiety scores
      was partialled out from change in somatosensory amplification scores, the
      amplification scores did not change significantly in either the depressed or the
      fibromyalgia groups. Given the small numbers and the marginal significance of the
      results, the authors are unable to say definitely just how independent of
      depression somatosensory amplification is. Whether somatosensory amplification is
      a measure of depression per se should be tested in a more definitive and larger
      future study.

PMID- 16000678
TI  - Duloxetine for the treatment of major depressive disorder in women ages 40 to 55
      years.
AB  - The efficacy of duloxetine in the treatment of major depressive disorder in women
      of approximately perimenopausal age (40-55 years; 62 placebo subjects and 55
      subjects taking duloxetine, 60 mg/day) was compared with that observed in cohorts
      of younger (<40 years, 94 placebo subjects and 85 duloxetine subjects) and older
      (>55 years, 26 placebo subjects and 25 duloxetine subjects) women. Women (ages 40
      55 years) receiving duloxetine demonstrated significantly greater improvement in
      total scores on the 17-item Hamilton Rating Scale for Depression compared with
      placebo at the study endpoint (week 9). Significant advantages for duloxetine
      over placebo were observed on 17-item Hamilton depression scale subscales (core,
      Maier, anxiety, retardation, and sleep), in addition to the Clinical Global
      Impression severity and Patient Global Impression of Improvement Scale, the
      Quality of Life in Depression Scale, and Visual Analog Scales assessing pain
      severity. The magnitude of duloxetine's treatment effect in women ages 40-55
      years was similar to that observed in younger (age <40 years) and older (age >55
      years) female patients. In the placebo treatment groups, however, mean changes
      differed substantially by age group with the smallest placebo responses observed
      in the 40-55 age group. Duloxetine (60 mg/day) was demonstrated to be an
      effective treatment for major depressive disorder in this cohort of women ages 40
      55 years.

PMID- 16000679
TI  - Depression following acute myocardial infarction: a prospective relationship with
      ongoing health and function.
AB  - The relationship between baseline depression and health-related quality of life
      were examined in a cohort of patients after hospitalization due to acute
      myocardial infarction (N=196). Patients were assessed for presence of mood
      disturbance, anxiety, and quality of life at the time of hospitalization and
      again 4 months later. Baseline assessment was used to assign subjects to a
      depressed or a nondepressed group. Adjusting for preinfarction quality of life,
      in-hospital anxiety, and demographic variables, depression was prospectively and
      independently related to reduced global health at 4 months as well as reduced
      overall mental health-including vitality, psychological health, and social
      function-and increased role interference from psychological problems.

PMID- 16000680
TI  - Untreated trichotillomania and trichophagia: surgical emergency in a teenage
      girl.
AB  - Trichophagia secondary to trichotillomania can be a potentially life-threatening
      condition if left untreated. This report documents the unique case of a 16-year
      old girl whose untreated trichotillomania led to a trichobezoar requiring
      surgical intervention and follow-up psychiatric treatment. Challenges in the
      identification and treatment of the disorder and its complications are discussed
      as well as the importance of early and accurate diagnosis.

PMID- 16000681
TI  - Safety of trazodone as a sleep agent for inpatients.
AB  - Trazodone, an atypical antidepressant with relatively low anticholinergic and
      cardiac conduction effects, offers useful augmentation to classic antidepressant
      drugs, notably selective serotonin reuptake inhibitors. One rare but serious side
      effect of the drug is priapism, the urological emergency in which the cavernosa
      of the penis become painfully engorged in the absence of sexual stimulation. The
      authors present what appears to be the first published case of priapism requiring
      urologic intervention after a single 100-mg dose of trazodone. In addition to a
      discussion of the history and physiology of trazodone and priapism, the authors
      present a profile of patients who present a safety risk in treatment.

PMID- 16000682
TI  - Selective serotonin reuptake inhibitors and patients with carcinoid tumor.

PMID- 16000683
TI  - Alleviating the itch-scratch cycle in atopic dermatitis.

PMID- 16000684
TI  - Delirium resolving upon switching from risperidone to quetiapine: implication of
      CYP2D6 genotype.

PMID- 16000685
TI  - Odd SOD.

PMID- 16000686
TI  - Hair trigger.

PMID- 16000687
TI  - T-CIA: investigating T cells in aging.
AB  - Over the past few decades it has become clear that the immune system and
      especially T cells are instrumental in achieving a long and healthy life. The
      European Union (EU) previously supported several pan-European research projects
      coordinated from Tuebingen, Germany, aimed at providing a better understanding of
      immunosenescence. For 3 years, until the end of 2005, the EU is supporting a
      project called T cells in aging (T-CIA). The aim of T-CIA is to spy out and
      combine current efforts in immunology, molecular biology, and gerontology for a
      better understanding of why the elderly often have dysregulated immune responses
      and are more susceptible to infections and cancer.

PMID- 16000688
TI  - In one's own image: ethics and the reproduction of deafness.
AB  - The ethics of the use of genetic screening and reproductive technologies to
      select against and for deafness is presented. It is argued that insofar as
      deafness is a disability it is ethical to act in such a way as to avoid the
      conception or birth of children with genetic or congenital deafness. The
      discovery and recognition of signing deaf communities as cultural and linguistic
      communities (minorities) does not alter this basic ethical position, although the
      consequences of widespread application of this technology appears destined to
      lead to the eventual disappearance of these communities. The argument that acting
      to avoid deafness is unethical because it will lead to the elimination of a
      linguistic or cultural group (genocide or ethnocide) or conversely that acting to
      ensure deafness is ethical, if not praiseworthy, can only be sustained if
      deafness is not regarded as a disability at all. I argue that the premise that
      deafness is not a disability of some sort is false and thus the claim that
      genetic selection against deafness is unethical is untenable.

PMID- 16000689
TI  - Perception of sign language and its application to visual communications for deaf
      people.
AB  - Video communication systems for deaf people are limited in terms of quality and
      performance. Analysis of visual attention mechanisms for sign language may enable
      optimization of video coding systems for deaf users. Eye-movement tracking
      experiments were conducted with profoundly deaf volunteers while watching sign
      language video clips. Deaf people are found to fixate mostly on the facial region
      of the signer to pick up small detailed movements associated with facial
      expression and mouth shapes. Lower resolution, peripheral vision is used to
      process information from larger, rapid movements of the signer in the video
      clips. A coding scheme that gives priority to the face of the signer may be
      applied to improve perception of video quality for sign language communication.

PMID- 16000690
TI  - Models of deafness: cochlear implants in the Australian daily press.
AB  - This article examined a database of Australian daily newspapers on the terms
      cochlear implant and deaf children to investigate how journalists and columnists
      report competing models of deafness: as either "medical" (deafness is a condition
      to be cured) or "sociocultural" (deafness provides a way of life to be lived).
      The results from the cochlear implant search favored a medical model, but the
      results from the deaf children search were more balanced, with a slight
      preponderance of articles favoring the sociocultural model. A number of
      representative quotes from articles in each model are provided and discussion
      entered into as to the possible effects of the articles on public reactions to
      deafness and especially hearing parental responses to the birth of a deaf child
      and the life choices that this event presents them.

PMID- 16000691
TI  - Understanding Harry Potter: parallels to the deaf world.
AB  - Every so often there are stories that take the world by storm and make such an
      impact that they become part of our everyday world. These stories, characters,
      and themes become established elements of cultural literacy. This is exactly what
      has happened with J. K. Rowling's Harry Potter series. Harry and his cohort of
      wizards, witches, and their adventures have become an indispensable part of
      popular literature and popular culture. We have developed an innovative way to
      ensure that Deaf children, their families, and anyone studying literature (Deaf
      or general) gain a deeper understanding of this phenomenon. In fact, we go
      further by demonstrating how using a Deaf Lens provides the greatest insight into
      the fascinating world of Harry Potter. Utilizing a Deaf Studies Template and a
      Deaf Lens, we capitalize on the experiences of Deaf people everywhere while
      celebrating the valuable role American Sign Language has in academic programming.

PMID- 16000692
TI  - Violent offenders in a deaf prison population.
AB  - Previous research suggested an unexplained difference in the patterns of
      offending behaviors among deaf people when compared to hearing people. This
      study, conducted in Texas, compares the incidence and types of violent offenses
      of a deaf prison population in comparison to the hearing prison population. Sixty
      four percent of deaf prisoners were incarcerated for violent offenses in
      comparison to 49% of the overall state prison offender population. This finding
      is consistent with previous research. The most significant difference between the
      populations was found in the category of sexual assault, which represented 32.3%
      of deaf offenders in contrast to 12.3% of hearing state prison inmates overall.
      Factors potentially impacting violent offending by deaf persons are their
      vulnerability to child sexual abuse, use of chemicals, educational histories, and
      development of language and communication skills. Additionally, there is a
      widespread lack of accessible intervention and treatment services available to
      deaf sex offenders across the nation.

PMID- 16000693
TI  - The impact of visual communication on the intersubjective development of early
      parent-child interaction with 18- to 24-month-old deaf toddlers.
AB  - This article presents a study that examined the impact of visual communication on
      the quality of the early interaction between deaf and hearing mothers and fathers
      and their deaf children aged between 18 and 24 months. Three communication mode
      groups of parent-deaf child dyads that differed by the use of signing and visual
      tactile communication strategies were involved: (a) hearing parents communicating
      with their deaf child in an auditory/oral way, (b) hearing parents using total
      communication, and (c) deaf parents using sign language. Based on Loots and
      colleagues' intersubjective developmental theory, parent-deaf child interaction
      was analyzed according to the occurrence of intersubjectivity during free play
      with a standard set of toys. The data analyses indicated that the use of sign
      language in a sequential visual way of communication enabled the deaf parents to
      involve their 18- to 24-month-old deaf infants in symbolic intersubjectivity,
      whereas hearing parents who hold on to oral-only communication were excluded from
      involvement in symbolic intersubjectivity with their deaf infants. Hearing
      parents using total communication were more similar to deaf parents, but they
      still differed from deaf parents in exchanging and sharing symbolic and
      linguistic meaning with their deaf child.

PMID- 16000694
TI  - Early manual communication in relation to the deaf child's intellectual, social,
      and communicative functioning.
AB  - The basic impoverishment of deafness is not lack of hearing but lack of language.
      To illustrate this, we have only to compare a 4-year-old hearing child, with a
      working vocabulary of between 2,000 and 3,000 words, to a child of the same age,
      profoundly deaf since infancy, who may have only a few words at his command. Even
      more important than vocabulary level, however, is the child's ability to use his
      language for expressing ideas, needs, and feelings. By the age of 4 years, the
      hearing child in all cultures has already grasped the rules of grammar syntax
      that enable him or her to combine words in meaningful ways.

PMID- 16000695
TI  - Bisecting GlcNAc mediates the binding of annexin V to Hsp47.
AB  - The bisecting N-acetylglucosamine (GlcNAc) structure, formed through catalysis by
      UDP-N-acetylglucosamine : beta-D-mannoside beta-1,4-N
      acetylglucosaminyltansferase III (GnT-III), is responsible for a variety of
      biological functions. We have previously shown that annexin V, a member of the
      calcium/phospholipid-binding annexin family of proteins, has binding activity
      toward the bisecting GlcNAc structure. In this study, we reported on a search for
      potential target glycoproteins for annexin V in a rat hepatoma cell line, M31.
      Using a glutathione S-transferase (GST)-annexin V immobilized sepharose 4B
      affinity column to trap interacting proteins produced by the GnT-III-transfected
      M31 cells, we isolated a 47 kDa protein. It was identified as Hsp47 by an N
      terminal sequence analysis. Immunoprecipitation experiments showed that annexin V
      interacted with Hsp47. The association of annexin V and Hsp47 was abolished by
      treatment with N-glycosidase F or preincubation with sugar chains containing
      bisecting GlcNAc, suggesting that the bisecting GlcNAc plays an important role in
      the interaction. An oligosaccharide analysis of Hsp47 purified from GnT-III
      transfected M31 cells was shown to have the bisecting GlcNAc structure, as
      detected by erythroagglutinating phytohemagglutinin (E4-PHA) and matrix assisted
      laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS)
      analysis. Surface plasmon resonance analysis showed that annexin V was bound to
      Hsp47, bearing a bisecting GlcNAc with a Kd of 5.5 microM, whereas no significant
      binding was observed in the case of Hsp47 without a bisecting GlcNAc. In
      addition, immunofluorescence microscopy revealed the colocalization of annexin V,
      Hsp47, and a bisecting GlcNAc sugar chain around the Golgi apparatus.
      Collectively, these results suggest that the binding of annexin V to Hsp47 is
      mediated by a bisecting GlcNAc oligosaccharide structure and that Hsp47 is an
      intracellular ligand glycoprotein for annexin V.

PMID- 16000696
TI  - Molecular cloning and functional expression of a novel Helicobacter pylori alpha
      1,4 fucosyltransferase.
AB  - Helicobacter pylori is an important human pathogen which causes both gastric and
      duodenal ulcers and is associated with gastric cancer and lymphoma. This
      microorganism synthesizes fucosylated oligosaccharides, predominantly the Galb
      1,4GlcNAc (Type II) blood group antigens Lewis X and Y, whereas a small
      population also expresses the Galb-1,3GlcNAc (Type I) blood group antigens Lewis
      A and B. These carbohydrate structures are known to mimic host cell antigens and
      permit the bacteria to escape from the host immune response. Here, we report the
      cloning and characterization of a novel H. pylori alpha-1,4 fucosyltransferase
      (FucT). In contrast to the family members characterized to date, this enzyme
      shows exclusively Type I acceptor substrate specificity. The enzyme consisting of
      432 amino acids (MW 50,502 Da) was cloned using a polymerase chain reaction (PCR)
      based approach. It exhibits a high degree of identity (75-87%) and similar
      structural features, for example, in the heptamer repeat pattern, with other H.
      pylori FucTs. The kinetic characterization revealed a very efficient transferase
      (k(cat)/Km = 229 mM(-1) s(-1)) for the Type I acceptor substrate (Gal)-1,3 GlcNAc
      Lem (1). Additionally, the enzyme possesses a broad tolerance toward nonnatural
      Type I acceptor substrate analogs and therefore represents a valuable tool for
      the chemoenzymatic synthesis of Lewis A, sialyl Lewis A as well as mimetics
      thereof.

PMID- 16000697
TI  - Modification of oligosaccharides by reactive oxygen species decreases sialyl
      lewis x-mediated cell adhesion.
AB  - Modification of cell surface oligosaccharides by reactive oxygen species (ROS)
      and the biological effect of such modifications on cell adhesion were
      investigated. Treatment of HL60, a human promyelocyte leukemia cell line, with
      ROS, generated by a combination of hypoxanthine and xanthine oxidase (HX/XO),
      decreased the sialic acid content on the cell surface, as indicated by a flow
      cytometric analysis involving sialic acid-specific lectins, and a concomitant
      increase of free sialic acid was observed in the supernatant. A cell adhesion
      assay showed that the HX/XO treatment of HL60 cells decreases their capability of
      binding to human umbilical vein endothelial cells (HUVEC), probably because of an
      impairment of the interaction involving E-selectin, whereas the decrease in the
      binding was canceled by the addition of superoxide dismutase (SOD) and catalase.
      In fact, cell surface sialyl lewis x (sLe x), but not lewis x (Le x), was
      decreased by HX/XO treatment. Thus, it is more likely that the impaired
      interaction is based on diminished levels of the selectin ligand. Cleavage of
      sialic acid by ROS was further verified by the degradation of 4MU-Neu5Ac by HX/XO
      in the presence of hydrogen peroxide and iron ion. These results indicate that
      glycosidic linkage of sialic acid is a potential target for superoxide and other
      related ROS. It is well known that ROS cause cellular damages such as lipid
      peroxidation and protein oxidation, but, as suggested by the findings reported in
      the literature, ROS may also regulate cell adhesion via the structural alteration
      of sialylated oligosaccharides on the cell surface.

PMID- 16000698
TI  - Cytokines and sodium induce protein kinase A-dependent cell-surface Na,K-ATPase
      recruitment via dissociation of NF-kappaB/IkappaB/protein kinase A catalytic
      subunit complex in collecting duct principal cells.
AB  - Collecting duct (CD) principal cells are exposed to large physiologic variations
      of apical Na+ influx as a result of variations of Na(+) intake and extrarenal
      losses. It was shown previously that increasing intracellular [Na+] induces
      recruitment of Na,K-ATPase to the cell surface in a protein kinase A (PKA)
      dependent manner in both native and cultured renal CD principal cells. As
      described previously in response to cytokines in nonrenal cells, PKA activation
      in response to increased intracellular [Na+] was independent of cAMP and required
      proteasomal activity. With the use of cultured mpkCCD(cL4) cells as a model of CD
      principal cells, whether cytokines and increased intracellular [Na+] share a
      common signaling pathway leading to cell-surface Na,K-ATPase recruitment was
      investigated. Results showed that two potent inducers of NF-kappaB, LPS and TNF
      alpha, enhance Na+ transport and induce cell-surface Na,K-ATPase recruitment in
      mpkCCD(cL4) cells via cAMP-independent PKA activation. In addition, increased
      intracellular [Na+] after selective plasma membrane permeabilization by a low
      concentration of the Na+ ionophore amphotericin B (1 microg/ml) induced
      dissociation of the PKA catalytic subunit from p65-NF-kappaB and IkappaBalpha.
      Moreover, inhibitors of NF-kappaB/IkappaB dissociation prevented both Na+
      dependent stimulation of PKA activity and cell-surface Na,K-ATPase recruitment.
      Altogether, these results revealed the presence of a novel Na+-dependent
      intracellular signaling pathway leading to Na,K-ATPase cell-surface recruitment
      via dissociation of the PKA catalytic subunit from a macromolecular complex that
      contains NF-kappaB and IkappaBalpha in CD epithelial cells.

PMID- 16000699
TI  - Regulatory interdependence of cloned epithelial Na+ channels and P2X receptors.
AB  - Epithelial Na+ channels (ENaC) coexist with a family of ATP-gated ion channels
      known as P2X receptors in the renal collecting duct. Although ENaC is itself
      insensitive to extracellular ATP, tubular perfusion of ATP can modify the
      activity of ENaC. To investigate a possible regulatory relationship between P2X
      receptors and ENaC, coexpression studies were performed in Xenopus oocytes. ENaC
      generated a persistent inward Na+ current that was sensitive to the channel
      blocker amiloride (I(am-s)). Exogenous ATP transiently activated all cloned
      isoforms of P2X receptors, which in some cases irreversibly inhibited I(am-s).
      The degree of inhibition depended on the P2X receptor subtype present. Activation
      of P2X2, P2X(2/6), P2X4, and P2X(4/6) receptor subtypes inhibited I(am-s),
      whereas activation of P2X1, P2X3, and P2X5 receptors had no significant effect.
      The degree of inhibition of I(am-s) correlated positively with the amount of
      ionic charge conducted by P2X receptor subtypes. ENaC inhibition required Na+
      influx through I(am-s)-inhibiting P2X ion channels but also Ca2+ influx through
      P2X4 and P2X(4/6) ion channels. P2X-mediated inhibition of I(am-s) was found to
      be due to retrieval of ENaC from the plasma membrane. Maximum amplitudes of ATP
      evoked P2X-mediated currents (I(ATP)) were significantly increased for P2X2,
      P2X(2/6), and P2X5 receptor subtypes after coexpression of ENaC. The increase in
      I(ATP) was due to increased levels of plasma membrane-bound P2X receptor protein,
      suggesting that ENaC modulates protein trafficking. In summary, ENaC was
      downregulated by the activation of P2X2, P2X(2/6), P2X4, and P2X(4/6) receptors.
      Conversely, ENaC increased the plasma membrane expression of P2X2, P2X(2/6), and
      P2X5 receptors.

PMID- 16000700
TI  - Parathyroid hormone regulation of NA+,K+-ATPase requires the PDZ 1 domain of
      sodium hydrogen exchanger regulatory factor-1 in opossum kidney cells.
AB  - It was demonstrated that expression of murine sodium hydrogen exchanger
      regulatory factor (NHERF-1) lacking the ezrin-binding domain blocks parathyroid
      hormone (PTH) regulation of Na+,K+-ATPase in opossum kidney (OK) cells. The
      hypothesis that the NHERF-1 PDZ domains contribute to PTH regulation of Na+,K+
      ATPase was tested by comparison of PTH regulation of Na+,K+-ATPase in wild-type
      OK (OK-WT) cells, NHERF-deficient OKH cells, OK-WT transfected with siRNA for
      NHERF (NHERF siRNA OK-WT), and OKH cells that were stably transfected with full
      length NHERF-1 or constructs with mutated PDZ domains. OKH cells and NHERF siRNA
      OK-WT showed decreased expression of NHERF-1 but equivalent expression of ezrin
      and Na+,K+-ATPase alpha1 subunit when compared with OK-WT cells. PTH decreased
      Na+,K+-ATPase activity and stimulated phosphorylation of the Na+,K+-ATPase alpha1
      in OK-WT cells but not in NHERF-deficient cells. Rubidium (86Rb) uptake was
      equivalent in OK-WT, OKH, and OKH cells that were transfected with all but the
      double PDZ domain mutants. PTH decreased 86Rb uptake significantly in OK-WT but
      not in OKH cells. PTH also significantly inhibited 86Rb uptake in OKH cells that
      were transfected with full-length NHERF-1 or NHERF-1 with mutated PDZ 2 but not
      in OKH cells that were transfected with mutated PDZ 1. Transfection with NHERF
      expressing both mutated PDZ domains resulted in diminished basal 86Rb uptake that
      was not inhibited further by PTH. PTH stimulated protein kinase Calpha activity
      and alpha1 subunit phosphorylation in OK-WT but not in NHERF-deficient cells.
      Transfection of OKH cells with NHERF constructs that contained an intact PDZ1
      domain restored PTH-stimulated protein kinase Calpha activity and alpha1 subunit
      phosphorylation. These results demonstrate that NHERF-1 is necessary for PTH
      mediated inhibition of Na+,K+-ATPase activity and that the inhibition is mediated
      through the PDZ1, not PDZ2, domain.

PMID- 16000701
TI  - Genome update: prediction of membrane proteins in prokaryotic genomes.

PMID- 16000702
TI  - The cereulide genetic determinants of emetic Bacillus cereus are plasmid-borne.

PMID- 16000703
TI  - Databases and software for the comparison of prokaryotic genomes.
AB  - The explosion in the number of complete genomes over the past decade has spawned
      a new and exciting discipline, that of comparative genomics. To exploit the full
      potential of this approach requires the development of novel algorithms,
      databases and software which are sophisticated enough to draw meaningful
      comparisons between complete genome sequences and are widely accessible to the
      scientific community at large. This article reviews progress towards the
      development of computational tools and databases for organizing and extracting
      biological meaning from the comparison of large collections of genomes.

PMID- 16000704
TI  - Phage therapy: the Escherichia coli experience.
AB  - Phages have been proposed as natural antimicrobial agents to fight bacterial
      infections in humans, in animals or in crops of agricultural importance. Phages
      have also been discussed as hygiene measures in food production facilities and
      hospitals. These proposals have a long history, but are currently going through a
      kind of renaissance as documented by a spate of recent reviews. This review
      discusses the potential of phage therapy with a specific example, namely
      Escherichia coli.

PMID- 16000706
TI  - Recovery from long-term stationary phase and stress survival in Escherichia coli
      require the L-isoaspartyl protein carboxyl methyltransferase at alkaline pH.
AB  - The L-isoaspartyl protein carboxyl methyltransferase (pcm) can stimulate repair
      of isoaspartyl residues arising spontaneously in proteins to normal L-aspartyl
      residues. PCM is needed in Escherichia coli for maximal long-term survival when
      exposed to oxidative stress, osmotic stress, repeated heat stress or methanol.
      The effect of pH on a pcm mutant during long-term stationary phase was examined.
      PCM was not required for long-term survival of E. coli subjected to pH stress
      alone; however, PCM-deficient cells showed impaired resistance to paraquat and
      methanol only at elevated pH. The mutant also showed stress-survival phenotypes
      in minimal medium buffered to pH 9.0. Accumulation of isoaspartyl residues was
      accelerated at pH 8.0 or 9.0 in vivo, though PCM-deficient cells did not show
      higher levels of damage. However, the pcm mutant displayed an extended lag phase
      in recovering from stationary phase at pH 9.0. Protein repair by PCM thus plays a
      key role in long-term stress survival only at alkaline pH in E. coli, and it may
      function primarily to repair damage in cells that are recovering from nutrient
      limitation and in those cells that are able to divide during long-term stationary
      phase.

PMID- 16000705
TI  - Application of multilocus sequence analysis (MLSA) for rapid identification of
      Enterococcus species based on rpoA and pheS genes.
AB  - The aim of this study was to evaluate the use of RNA polymerase alpha subunit
      (rpoA) and phenylalanyl-tRNA synthase (pheS) gene sequences as species
      identification tools for enterococci. Ninety-six representative strains
      comprising all currently recognized Enterococcus species were examined. rpoA gene
      sequences generated a robust classification into species groups similar to the
      one based on 16S rRNA gene sequence analysis. On the other hand, the pheS gene is
      a fast-evolving clock even better suited for species delineation than the rpoA
      gene, but not for recognition of species groups within Enterococcus as determined
      by both rpoA and 16S rRNA genes. All enterococcal species were clearly
      differentiated on the basis of their rpoA and pheS sequences. Evaluation of
      intraspecies variation showed that both rpoA and pheS genes have a high degree of
      homogeneity among strains of the same species. Strains of the same enterococcal
      species have at least 99% rpoA and 97% pheS gene sequence similarity, whereas,
      different enterococcal species have at maximum 97% rpoA and 86% pheS gene
      sequence similarity. It was concluded that both genes can be used as reliable
      tools for identification of clinical and environmental species of Enterococcus
      and are efficient screening methods for the detection of novel species. The
      sequence data obtained in this study were compared to the available atpA and 16S
      rRNA gene sequences. The MLSA approach to Enterococcus taxonomy provides
      portable, highly reproducible data with lower costs for rapid identification of
      all enterococcal species.

PMID- 16000707
TI  - Distribution and evolution of multiple-step phosphorelay in prokaryotes: lateral
      domain recruitment involved in the formation of hybrid-type histidine kinases.
AB  - Although most two-component signal transduction systems use a simple
      phosphotransfer pathway from one histidine kinase (HK) to one response regulator
      (RR), a multiple-step phosphorelay involving a phosphotransfer scheme of His-Asp
      His-Asp was also discovered. Central to this multiple-step-type signal
      transduction pathway are a hybrid-type HK, containing both an HK domain and an RR
      receiver domain in a single protein, and a histidine-containing phosphotransfer
      (HPT) that can exist either as a domain in hybrid-type HKs or as a separate
      protein. Although multiple-step phosphorelay systems are predominant in
      eukaryotes, it has been previously suggested that they are less common in
      prokaryotes. In this study, it was found that putative hybrid-type HKs were
      present in 56 of 156 complete prokaryotic genomes, indicating that multiple-step
      phosphorelay systems are more common in prokaryotes than previously appreciated.
      Large expansions of hybrid-type HKs were observed in 26 prokaryotic species,
      including photosynthetic cyanobacteria such as Nostoc sp. PCC 7120, and several
      pathogenic bacteria such as Coxiella burnetii. Phylogenetic analysis indicated
      that there was no common ancestor for hybrid-type HKs, and their origin and
      expansion was achieved by lateral recruitment of a receiver domain into an HK
      molecule and then duplication as one unit. Lateral recruitment of additional
      sensory domains such as PAS was also evident. HPT domains or proteins were
      identified in 32 of the genomes with hybrid-type HKs; however, no significant
      gene expansion was observed for HPTs even in a genome with a large number of
      hybrid-type HKs. In addition, fewer HPTs than hybrid-type HKs were identified in
      all prokaryotic genomes.

PMID- 16000708
TI  - Predicted highly expressed genes in the genomes of Streptomyces coelicolor and
      Streptomyces avermitilis and the implications for their metabolism.
AB  - Highly expressed genes in bacteria often have a stronger codon bias than genes
      expressed at lower levels, due to translational selection. In this study, a
      comparative analysis of predicted highly expressed (PHX) genes in the
      Streptomyces coelicolor and Streptomyces avermitilis genomes was performed using
      the codon adaptation index (CAI) as a numerical estimator of gene expression
      level. Although it has been suggested that there is little heterogeneity in codon
      usage in G+C-rich bacteria, considerable heterogeneity was found among genes in
      these two G+C-rich Streptomyces genomes. Using ribosomal protein genes as
      references, approximately 10% of the genes were predicted to be PHX genes using a
      CAI cutoff value of greater than 0.78 and 0.75 in S. coelicolor and S.
      avermitilis, respectively. The PHX genes showed good agreement with the
      experimental data on expression levels obtained from proteomic analysis by
      previous workers. Among 724 and 730 PHX genes identified from S. coelicolor and
      S. avermitilis, 368 are orthologue genes present in both genomes, which were
      mostly 'housekeeping' genes involved in cell growth. In addition, 61 orthologous
      gene pairs with unknown functions were identified as PHX. Only one polyketide
      synthase gene from each Streptomyces genome was predicted as PHX. Nevertheless,
      several key genes responsible for producing precursors for secondary metabolites,
      such as crotonyl-CoA reductase and propionyl-CoA carboxylase, and genes necessary
      for initiation of secondary metabolism, such as adenosylmethionine synthetase,
      were among the PHX genes in the two Streptomyces species. The PHX genes exclusive
      to each genome, and what they imply regarding cellular metabolism, are also
      discussed.

PMID- 16000709
TI  - Determining the functionality of putative Tat-dependent signal peptides in
      Streptomyces coelicolor A3(2) by using two different reporter proteins.
AB  - The availability of the complete genome sequence of Streptomyces coelicolor A3(2)
      has allowed the prediction of the Tat-exported proteins of this Gram-positive
      bacterium. To predict secreted proteins that potentially use the Tat pathway for
      their secretion, the TATscan program was developed. This program identified 129
      putative Tat substrates. To test the validity of these predictions, nine signal
      sequences, including three which were not identified by existing prediction
      programs, were selected and fused to the structural xlnC gene in place of its
      native signal sequence. Xylanase C (XlnC) is a cofactorless enzyme which is
      secreted in an active form exclusively through the Tat-dependent pathway by
      Streptomyces lividans. Among the nine chosen signal sequences, seven were shown
      to be Tat-dependent, one was Sec-dependent and one was probably not a signal
      sequence. The seven Tat-dependent signal sequences comprised two lipoprotein
      signal sequences and three sequences not predicted by previous programs. Pulse
      chase experiments showed that the precursor-processing rate in the seven
      transformants was generally slower than wild-type XlnC, indicating that these
      signal peptides were not equivalent in secretion. This suggested that there might
      be some incompatibility between the signal peptide and the reporter protein fused
      to it. To test this possibility, the signal peptides were fused to a cofactorless
      chitosanase (SCO0677), a Tat-dependent protein validated in this work but
      structurally different from XlnC. With some fluctuations, similar results were
      obtained with this enzyme, indicating that the type of folding of the reporter
      protein had little effect on the Tat secretion process.

PMID- 16000710
TI  - Overproduction, purification and characterization of FtmPT1, a brevianamide F
      prenyltransferase from Aspergillus fumigatus.
AB  - A putative prenyltransferase gene, ftmPT1, was identified in the genome sequence
      of Aspergillus fumigatus. ftmPT1 was cloned and expressed in Escherichia coli,
      and the protein FtmPT1 was purified to near homogeneity and characterized
      biochemically. This enzyme was found to catalyse the prenylation of cyclo-L-trp-L
      Pro (brevianamide F) at the C-2 position of the indole nucleus. FtmPT1 is a
      soluble monomeric protein, which does not contain the usual prenyl diphosphate
      binding site (N/D)DXXD found in most prenyltransferases, and which does not
      require divalent metal ions for its enzymic activity. K(m) values for
      brevianamide F and dimethylallyl diphosphate were determined as 55 and 74 microM,
      respectively. The turnover number was 5.57 s(-1). FtmPT1 showed a high substrate
      specificity towards dimethylallyl diphosphate, but accepted different tryptophan
      containing cyclic dipeptides. Together with dimethylallyltryptophan synthase of
      ergot alkaloid biosynthesis, FtmPT1 belongs to a new group of prenyltransferases
      with aromatic substrates.

PMID- 16000711
TI  - CreA influences the metabolic fluxes of Aspergillus nidulans during growth on
      glucose and xylose.
AB  - The physiological phenotype of Aspergillus nidulans was investigated for
      different genetic and environmental conditions of glucose repression through the
      quantification of in vivo fluxes in the central carbon metabolism using (13)C
      metabolic-flux analysis. The particular focus was the role of the carbon
      repressor CreA, which is the major regulatory protein mediating carbon repression
      in many fungal species, in the primary metabolism of A. nidulans. Batch
      cultivations were performed with a reference strain and a deletion mutant strain
      (creADelta4) using [1-(13)C]glucose as carbon source. The mutant strain was also
      grown on a mixture of [1-(13)C]glucose and unlabelled xylose. Fractional
      enrichment data were measured by gas chromatography-mass spectrometry. A model
      describing the central metabolism of A. nidulans was used in combination with
      fractional enrichment data, and measurements of extracellular rates and biomass
      composition for the estimation of the in vivo metabolic fluxes. The creA-mutant
      strain showed a lower maximum specific growth rate than the reference strain when
      grown on glucose (0.11 and 0.25 h(-1), respectively), whereas the specific growth
      rate of the mutant strain grown on the glucose/xylose mixture was identical to
      that on glucose (0.11 h(-1)). Different patterns and increased levels of
      extracellular polyols were observed both upon deletion of the creA gene and upon
      addition of xylose to the growth medium of the mutant strain. Concerning
      metabolic fluxes, the major change observed in the flux distribution of A.
      nidulans upon deletion of the creA gene was a 20 % decrease in the flux through
      the oxidative part of the pentose-phosphate pathway. Addition of xylose to the
      growth medium of the mutant resulted in an increase of about 40 % in the activity
      of the oxidative part of the pentose-phosphate pathway, as well as decreases in
      the fluxes through the Embden-Meyerhof-Parnas pathway and the tricarboxylic acid
      cycle (in the range of 20-30 %). The derepression of key pathways leads to
      alterations in the demands for cofactors, thereby imposing changes in the central
      metabolism due to the coupling of the many different reactions via the redox and
      energy metabolism of the cells.

PMID- 16000712
TI  - A putative dual-specific protein phosphatase encoded by YVH1 controls growth,
      filamentation and virulence in Candida albicans.
AB  - In response to stimulants, such as serum, the yeast cells of the opportunistic
      fungal pathogen Candida albicans form germ tubes, which develop into hyphae.
      Yvh1p, one of the 29 protein phosphatases encoded in the C. albicans genome, has
      45% identity with the dual-specific phosphatase Yvh1p of the model yeast
      Saccharomyces cerevisiae. In this study, Yvh1p expression was not observed during
      the initial step of germ tube formation, although Yvh1p was expressed
      constitutively in cell cycle progression of yeast or hyphal cells. In an attempt
      to analyse the function of Yvh1p phosphatase, the complete ORFs of both alleles
      were deleted by replacement with hph200-URA3-hph200 and ARG4. Although YVH1 has
      nine single-nucleotide polymorphisms in its coding sequence, both YVH1 alleles
      were able to complement the YVH1 gene disruptant. The vegetative growth of
      Deltayvh1 was significantly slower than the wild-type. The hyphal growth of
      Deltayvh1 on agar, or in a liquid medium, was also slower than the wild-type
      because of the delay in nuclear division and septum formation, although germ tube
      formation was similar between the wild-type and the disruptant. Despite the slow
      hyphal growth, the expression of several hypha-specific genes in Deltayvh1 was
      not delayed or repressed compared with that of the wild-type. Infection studies
      using mouse models revealed that the virulence of Deltayvh1 was less than that of
      the wild-type. Thus, YVH1 contributes to normal vegetative yeast or hyphal cell
      cycle progression and pathogenicity, but not to germ tube formation.

PMID- 16000713
TI  - Glutathione-dependent extracellular ferric reductase activities in dimorphic
      zoopathogenic fungi.
AB  - In this study, extracellular glutathione-dependent ferric reductase (GSH-FeR)
      activities in different dimorphic zoopathogenic fungal species were
      characterized. Supernatants from Blastomyces dermatitidis, Histoplasma
      capsulatum, Paracoccidioides brasiliensis and Sporothrix schenckii strains grown
      in their yeast form were able to reduce iron enzymically with glutathione as a
      cofactor. Some variations in the level of reduction were noted amongst the
      strains. This activity was stable in acidic, neutral and slightly alkaline
      environments and was inhibited when trivalent aluminium and gallium ions were
      present. Using zymography, single bands of GSH-FeRs with apparent molecular
      masses varying from 430 to 460 kDa were identified in all strains. The same
      molecular mass range was determined by size exclusion chromatography. These data
      demonstrate that dimorphic zoopathogenic fungi produce and secrete a family of
      similar GSH-FeRs that may be involved in the acquisition and utilization of iron.
      Siderophore production by these and other fungi has sometimes been considered to
      provide a full explanation of iron acquisition in these organisms. Our work
      reveals an additional common mechanism that may be biologically and
      pathogenically important. Furthermore, while some characteristics of these
      enzymes such as extracellular location, cofactor utilization and large size are
      not individually unique, when considered together and shared across a range of
      fungi, they represent an important novel physiological feature.

PMID- 16000714
TI  - The 'yeast cell wall chip' - a tool to analyse the regulation of cell wall
      biogenesis in Saccharomyces cerevisiae.
AB  - Within the field of Saccharomyces cerevisiae functional genomics, DNA microarrays
      have become a very useful tool to study genome-wide gene-expression changes under
      diverse experimental conditions. Here, the design and production of a gene
      microarray, called the 'yeast cell wall chip', specifically tailored to
      investigate cell wall functions, is described. This array has been validated and
      shown to be useful to address gene involvement in the regulation of the response
      to cell wall damage in yeast. The advantages of this tailored gene microarray,
      which contains 390 genes, in terms of reproducibility, accuracy, versatility and
      ease of use are reported. Importantly, the microarray design permits the
      performance of a double hybridization process (two experiments) on the same
      slide. Cell wall stress leads to the transcriptional activation of a set of genes
      involved in cell wall remodelling. This response has been shown to be strongly
      controlled by the MAP kinase (MAPK) Slt2p, but other signalling pathways have
      also been suggested to be involved in this process. Here, using the tailored
      microarray, the role of the HOG1 pathway in the regulation of the transcriptional
      compensatory response to cell wall damage was evaluated by comparing the
      transcriptional profiles of a hog1 mutant and a wild-type strain in the presence
      of Congo red. Two genes, YFL014W (HSP12) and YLR414C, were found to be dependent
      on the Hog1p MAPK for their induction, indicating that an additional level of
      regulation of cell wall functions is mediated by this MAPK.

PMID- 16000715
TI  - Prc protease promotes mucoidy in mucA mutants of Pseudomonas aeruginosa.
AB  - Mucoid strains of Pseudomonas aeruginosa that overproduce the exopolysaccharide
      alginate are a frequent cause of chronic respiratory infections in cystic
      fibrosis (CF) patients. The overproduction of alginate by these strains is often
      caused by mutations within mucA of the algU mucABCD gene cluster. This gene
      cluster encodes an extreme stress response system composed of the ECF alternative
      sigma factor AlgU, the anti-sigma factor MucA located in the inner membrane and
      the negative regulator MucB located in the periplasm. Most of the mutations in
      mucA found in mucoid strains cause a truncation of the C-terminal, periplasmic
      domain of MucA. The most significant effect of these mutations appears to be to
      reduce the levels of MucA. PA3257 (prc) was identified as a regulator of alginate
      production in P. aeruginosa through the isolation and study of mutations that
      partially suppressed the mucoid phenotype of a mucA22 strain. The suppressor of
      mucoidy (som) mutants isolated produced very little alginate when grown on LB
      medium, but were still mucoid when grown on Pseudomonas isolation agar. These som
      mutations and another previously isolated suppressor mutation were complemented
      by cosmids or plasmids carrying PA3257. PA3257 is predicted to encode a
      periplasmic protease similar to Prc or Tsp of Escherichia coli. Sequencing of prc
      from three strains with som suppressor mutations confirmed that each had a
      mutation within the prc coding region. The authors propose that Prc acts to
      degrade mutant forms of MucA. Additional evidence in support of this hypothesis
      is: (1) transcription from the AlgU-regulated algD reporter was reduced in som
      mutants; (2) inactivation of prc affected alginate production in mucoid strains
      with other mucA mutations found in CF isolates; (3) inactivation or
      overexpression of prc did not affect alginate production in strains with wild
      type MucA.

PMID- 16000716
TI  - Effect of static growth and different levels of environmental oxygen on toxA and
      ptxR expression in the Pseudomonas aeruginosa strain PAO1.
AB  - Within certain infection sites, such as the lung of cystic fibrosis patients,
      Pseudomonas aeruginosa grows statically under either decreased oxygen tension or
      anaerobic conditions, a situation that is likely to influence the production of
      virulence factors. The goal of this study was to determine the effect of static
      growth under microaerobic (decreased oxygen) and anaerobic conditions on the
      expression of the P. aeruginosa exotoxin A (ETA) gene toxA and its positive
      regulator ptxR. Using toxA-lacZ and ptxR-lacZ fusion plasmids, the level of toxA
      and ptxR expression was measured throughout the growth cycle of strain PAO1,
      which was grown in either iron-deficient or iron-sufficient medium under four
      different conditions: 20%-SH (aerobic, shaking), 20%-ST (aerobic, static), 10%-ST
      (microaerobic, static) and 0%-ST (anaerobic, static). In iron-deficient medium,
      toxA expression was higher under 20%-ST and 10%-ST than under 20%-SH. However,
      the highest level of toxA expression occurred under 0%-ST. Analysis of ETA
      protein using sandwich ELISA revealed that at time points between 8 and 24 h of
      the growth curve, PAO1 produced higher levels of ETA under 0%-ST than under 20%
      SH. In iron-sufficient medium, toxA expression was significantly repressed under
      all conditions. Additional analyses using PAO1 strains that carry lacZ fusions
      with the toxA regulatory genes regA and pvdS revealed that the expression of regA
      and pvdS is reduced rather than increased at 0%-ST. ptxR expression under
      different conditions paralleled that of toxA expression, except that it was
      repressed by iron under 20 %-SH only. Between 6 and 24 h of growth, and under all
      conditions, the level of dissolved oxygen (DO) within the PAO1 cultures was
      sharply reduced. These results suggest that (1) the combined effect of static
      growth and anaerobic conditions produce a significant increase in toxA and ptxR
      expression in PAO1; (2) this effect appears to be unique to toxA and ptxR, since
      the level of regA and pvdS expression was reduced under the same conditions; (3)
      neither static growth nor anaerobic conditions interfere with the repression of
      toxA expression by iron, although static growth deregulates ptxR expression with
      respect to iron; and (4) the enhanced expression of toxA and ptxR is not related
      to the reduced levels of DO in PAO1 cultures.

PMID- 16000717
TI  - Utilization of geraniol is dependent on molybdenum in Pseudomonas aeruginosa:
      evidence for different metabolic routes for oxidation of geraniol and
      citronellol.
AB  - Mini-Tn5-induced mutants with defects in utilization of linear terpenes such as
      citronellol, geraniol, citronellate and/or geranylate were isolated from
      Pseudomonas aeruginosa. One mutant was unable to utilize geraniol but showed wild
      type growth with the three other acyclic terpenes tested. The Tn5 insertion site
      of the mutant was determined by DNA sequencing. Comparison with the P. aeruginosa
      genome sequence revealed that PA3028, an ORF with high similarity on the amino
      acid level to molybdenum cofactor biosynthesis protein A2 (encoded by moeA2), was
      the target of mini-Tn5 in the mutant. Disruption of moeA2 in P. aeruginosa PAO1
      wild-type by insertion mutagenesis resulted in the same geraniol-minus phenotype.
      The ability to utilize geraniol was restored to the mutant by conjugative
      transfer of PCR-cloned wild-type moeA2 on a broad-host-range plasmid. Growth of
      P. aeruginosa PAO1 on geraniol and geranial, but not on citronellol, citronellate
      or geranylate, was inhibited by the presence of 10 mM tungstate, a molybdenum
      specific inhibitor. Inhibition by tungstate was prevented by addition of
      molybdate. The results indicate that at least one step in the oxidation of
      geraniol to geranic acid (geranial oxidation) is a molybdenum-dependent reaction
      in P. aeruginosa and is different from the molybdenum-independent oxidation of
      citronellol to citronellate.

PMID- 16000718
TI  - Multiple genotypes of Chlamydia pneumoniae identified in human carotid plaque.
AB  - Chlamydia pneumoniae is an obligate intracellular respiratory pathogen that
      causes 10 % of community-acquired pneumonia and has been associated with
      cardiovascular disease. Both whole-genome sequencing and specific gene typing
      suggest that there is relatively little genetic variation in human isolates of C.
      pneumoniae. To date, there has been little genomic analysis of strains from human
      cardiovascular sites. The genotypes of C. pneumoniae present in human
      atherosclerotic carotid plaque were analysed and several polymorphisms in the
      variable domain 4 (VD4) region of the outer-membrane protein-A (ompA) gene and
      the intergenic region between the ygeD and uridine kinase (ygeD-urk) genes were
      found. While one genotype was identified that was the same as one reported
      previously in humans (respiratory and cardiovascular), another genotype was found
      that was identical to a genotype from non-human sources (frog/koala).

PMID- 16000719
TI  - DNA methylation in Yersinia enterocolitica: role of the DNA adenine
      methyltransferase in mismatch repair and regulation of virulence factors.
AB  - DNA adenine methyltransferase (Dam) plays an important role in physiological
      processes of Gram-negative bacteria such as mismatch repair and replication. In
      addition, Dam regulates the expression of virulence genes in various species. The
      authors cloned the dam gene of Yersinia enterocolitica and showed that Dam is
      essential for viability. Dam overproduction in Y. enterocolitica resulted in an
      increased frequency of spontaneous mutation and decreased resistance to 2
      aminopurine; however, these effects were only marginal compared to the effect of
      overproduction of Escherichia coli-derived Dam in Y. enterocolitica, implying
      different roles or activities of Dam in mismatch repair of the two species. These
      differences in Dam function are not the cause for the essentiality of Dam in Y.
      enterocolitica, as Dam of E. coli can complement a dam defect in Y.
      enterocolitica. Instead, Dam seems to interfere with expression of essential
      genes. Furthermore, Dam mediates virulence of Y. enterocolitica. Dam
      overproduction results in increased tissue culture invasion of Y. enterocolitica,
      while the expression of specifically in vivo-expressed genes is not altered.

PMID- 16000720
TI  - Role of type III secretion in Edwardsiella tarda virulence.
AB  - Edwardsiella tarda is a Gram-negative enteric bacterium affecting both animals
      and humans. Recently, a type III secretion system (TTSS) was found in Ed. tarda.
      Such systems are generally used by bacterial pathogens to deliver virulence
      factors into host cells to subvert normal cell functions. Genome-walking was
      performed from the eseB and esrB genes (homologues of Salmonella sseB and ssrB,
      respectively) identified in previous studies, to determine the sequences of the
      TTSS. Thirty-five ORFs were identified which encode the TTSS apparatus,
      chaperones, effectors and regulators. Mutants affected in genes representing each
      category were generated and found to have decreased survival and growth in fish
      phagocytes. LD(50) values of the mutants were increased by at least 10-fold in
      comparison to those of the wild-type strain. The adherence and invasion rates of
      the esrA and esrB mutants were enhanced while those of the other mutants remained
      similar to the wild-type. The eseC and eseD mutants showed slight autoaggregation
      in Dulbecco's Modified Eagle Medium, whereas the rest of the mutants failed to
      autoaggregate. Regulation of the TTSS was found to involve the two-component
      regulatory system esrA-esrB. This study showed that the TTSS is important for Ed.
      tarda pathogenesis. An understanding of this system will provide greater insight
      into the virulence mechanisms of this bacterial pathogen.

PMID- 16000721
TI  - Substitutions in the interdomain loop of the Tn10 TetA efflux transporter alter
      tetracycline resistance and substrate specificity.
AB  - Cysteine replacement of Asp190, Glu192 and Ser201 residues in the cytoplasmic
      interdomain loop of the TetA(B) tetracycline efflux antiporter from Tn10 reduces
      tetracycline resistance [Tamura, N., Konishi, S., Iwaki, S., Kimura-Someya, T.,
      Nada, S. & Yamaguchi, A. (2001). J Biol Chem 276, 20330-20339]. It was found that
      these Cys substitutions altered the substrate specificity of TetA(B), increasing
      the relative resistance to doxycycline and minocycline over that to tetracycline
      by three- to sixfold. Substitutions of Asp190 and Glu192 by Ala, Asn and Gln also
      impaired the ability of TetA(B) to mediate tetracycline resistance while
      Ser201Ala and Ser201Thr substitutions did not. A Leu9Phe substitution in the
      first transmembrane helix of TetA(B) suppressed the Ser201Cys mutation, undoing
      the alterations in resistance and specificity. That the interdomain loop might
      contact substrate during transport, as is suggested from its role in substrate
      specificity, is unexpected considering that the primary sequence in the loop is
      not conserved among a group of otherwise homologous TetA proteins. However, in
      the interdomain loop of 11 of 14 homologous TetA efflux proteins, computational
      analysis revealed a short alpha-helix, which includes some residues affecting
      activity and substrate specificity. Perhaps this conserved secondary structure
      accounts for the role of the non-conserved interdomain loop in TetA function.

PMID- 16000722
TI  - Genetic characterization of the beta-glucuronidase enzyme from a human intestinal
      bacterium, Ruminococcus gnavus.
AB  - beta-Glucuronidase activity (encoded by the gus gene) has been characterized for
      the first time from Ruminococcus gnavus E1, an anaerobic bacterium belonging to
      the dominant human gut microbiota. beta-Glucuronidase activity plays a major role
      in the generation of toxic and carcinogenic metabolites in the large intestine,
      as well as in the absorption and enterohepatic circulation of many aglycone
      residues with protective effects, such as lignans, flavonoids, ceramide and
      glycyrrhetinic acid, that are liberated by the hydrolysis of the corresponding
      glucuronides. The complete nucleotide sequence of a 4537 bp DNA fragment
      containing the beta-glucuronidase locus from R. gnavus E1 was determined. Five
      ORFs were detected on this fragment: three complete ORFs (ORF2, gus and ORF3) and
      two partial ORFs (ORF4 and ORF5). The products of ORF2 and ORF3 show strong
      similarities with many beta-glucoside permeases of the phosphoenolpyruvate : beta
      glucoside phosphotransferase systems (PTSs), such as Escherichia coli BglC,
      Bacillus subtilis BglP and Bacillus halodurans PTS Enzyme II. The product of ORF5
      presents strong similarities with the amino-terminal domain of Clostridium
      acetobutylicum beta-glucosidase (bglA). The gus gene product presents
      similarities with several known beta-glucuronidase enzymes, including those of
      Lactobacillus gasseri (69%), E. coli (61%), Clostridium perfringens (59%) and
      Staphylococcus aureus (58%). By complementing an E. coli strain in which the uidA
      gene encoding the enzyme was deleted, it was confirmed that the R. gnavus gus
      gene encodes the beta-glucuronidase enzyme. Moreover, it was found that the gus
      gene was transcribed as part of an operon that includes ORF2, ORF3 and ORF5.

PMID- 16000723
TI  - Functional analysis of the lysis genes of Staphylococcus aureus phage P68 in
      Escherichia coli.
AB  - Double-stranded DNA phages of both Gram-positive and Gram-negative bacteria
      typically use a holin-endolysin system to achieve lysis of their host. In this
      study, the lysis genes of Staphylococcus aureus phage P68 were characterized. P68
      gene lys16 was shown to encode a cell-wall-degrading enzyme, which causes cell
      lysis when externally added to clinical isolates of S. aureus. Another gene,
      hol15, was identified embedded in the -1 reading frame at the 3' end of lys16.
      The deduced Hol15 protein has three putative transmembrane domains, and thus
      resembles class I holins. An additional candidate holin gene, hol12, was found
      downstream of the endolysin gene lys16 based on two predicted transmembrane
      domains of the encoded protein, which is a typical trait of class II holins. The
      synthesis of either Hol12 or Hol15 resulted in growth retardation of Escherichia
      coli, and both hol15 and hol12 were able to complement a phage lambda Sam
      mutation. The hol15 gene has a dual start motif beginning with the codons Met1
      Lys2-Met3.... Evidence is presented that the hol15 gene encodes a lysis inhibitor
      (anti-holin) and a lysis effector (actual holin). As depolarization of the
      membrane converted the anti-holin to a functional holin, these studies suggested
      that hol15 functions as a typical dual start motif class I holin. The unusual
      arrangement of the P68 lysis genes is discussed.

PMID- 16000724
TI  - Acd, a peptidoglycan hydrolase of Clostridium difficile with N
      acetylglucosaminidase activity.
AB  - A gene encoding a putative peptidoglycan hydrolase was identified by sequence
      similarity searching in the Clostridium difficile 630 genome sequence, and the
      corresponding protein, named Acd (autolysin of C. difficile) was expressed in
      Escherichia coli. The deduced amino acid sequence of Acd shows a modular
      structure with two main domains: an N-terminal domain exhibiting repeated
      sequences and a C-terminal catalytic domain. The C-terminal domain exhibits
      sequence similarity with the glucosaminidase domains of Staphylococcus aureus Atl
      and Bacillus subtilis LytD autolysins. Purified recombinant Acd produced in E.
      coli was confirmed to be a cell-wall hydrolase with lytic activity on the
      peptidoglycan of several Gram-positive bacteria, including C. difficile. The
      hydrolytic specificity of Acd was studied by RP-HPLC analysis and MALDI-TOF MS
      using B. subtilis cell-wall extracts. Muropeptides generated by Acd hydrolysis
      demonstrated that Acd hydrolyses peptidoglycan bonds between N-acetylglucosamine
      and N-acetylmuramic acid, confirming that Acd is an N-acetylglucosaminidase. The
      transcription of the acd gene increased during vegetative cellular growth of C.
      difficile 630. The sequence of the acd gene appears highly conserved in C.
      difficile strains. Regarding deduced amino acid sequences, the C-terminal domain
      with enzymic function appears to be the most conserved of the two main domains.
      Acd is the first known autolysin involved in peptidoglycan hydrolysis of C.
      difficile.

PMID- 16000725
TI  - Clostridium pasteurianum W5 synthesizes two NifH-related polypeptides under
      nitrogen-fixing conditions.
AB  - Previous studies identified five nifH-like genes (nifH2 through nifH6) in
      Clostridium pasteurianum (strain W5), where the nifH1 gene encodes the
      nitrogenase iron protein. Transcripts of these nifH genes, with the exception of
      nifH3, were detected in molybdenum-sufficient nitrogen-fixing cells. However, the
      size of the transcripts, the level of transcription and the presence of
      polypeptides encoded by the nifH-like genes were not reported. The nifH2 and
      nifH6 genes were extremely similar, as they seemed to differ by only two bases in
      a span of 2481 bp, one in the coding region and another in the upstream region.
      Re-examination of the DNA sequences revealed that the coding region of nifH2 and
      nifH6 was identical, whereas the difference in the upstream region was confirmed.
      Results from the authors' ongoing study of the nif genes of single-colony
      isolates of C. pasteurianum suggest that the nifH6 designation should be
      eliminated. Here the size of mRNA from nifH2 and the detection of the NifH2
      polypeptide in nitrogen-fixing cells of C. pasteurianum are reported. Northern
      blot analysis of periodically collected nitrogen-fixing cells showed that the
      nifH1 and nifH2 mRNAs were present throughout growth. Addition of ammonium
      acetate repressed the transcription of both these genes similarly. Using an
      antiserum raised against NifH of Azotobacter vinelandii, two NifH-related bands
      were detected by Western blot analysis after electrophoretic separation of
      proteins in extracts of nitrogen-fixing C. pasteurianum cells. After separation
      of proteins by preparative SDS-PAGE, the NifH polypeptides were characterized by
      MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry) and by ES-MS/MS (electrospray tandem mass spectrometry) analyses.
      The results confirmed the presence of NifH2, in addition to NifH1, in nitrogen
      fixing C. pasteurianum cells.

PMID- 16000726
TI  - Functions of the siderophore esterases IroD and IroE in iron-salmochelin
      utilization.
AB  - The siderophore salmochelin is produced under iron-poor conditions by Salmonella
      and many uropathogenic Escherichia coli strains. The production of salmochelin, a
      C-glucosylated enterobactin, is dependent on the synthesis of enterobactin and
      the iroBCDEN gene cluster. An E. coli IroD protein with an N-terminal His-tag
      cleaved cyclic salmochelin S4 to the linear trimer salmochelin S2, the dimer
      salmochelin S1, and the monomers dihydroxybenzoylserine and C-glucosylated
      dihydroxybenzoylserine (salmochelin SX, pacifarinic acid). The periplasmic IroE
      protein was purified as a MalE-IroE fusion protein. This enzyme degraded
      salmochelin S4 and ferric-salmochelin S4 to salmochelin S2 and ferric-salmochelin
      S2, respectively. In E. coli, uptake of ferric-salmochelin S4 was dependent on
      the cleavage by IroE, and independent of the FepBDGC ABC transporter in the
      cytoplasmic membrane. IroC, which has similarities to ABC-multidrug-resistance
      proteins, was necessary for the uptake of salmochelin S2 from the periplasm into
      the cytoplasm. IroE did not function as a classical binding protein since
      salmochelin S2 was taken up in the absence of a functional IroE protein. IroC
      mediated the uptake of iron via enterobactin in a fepB mutant. IroE was also
      necessary in this case for the uptake of ferric-enterobactin, which indicated
      that only the linear degradation products of enterobactin were taken up via IroC.
      PfeE, the Pseudomonas aeruginosa IroE homologue, was cloned, and its enzymic
      activity was shown to be very similar to that of IroE. It is suggested that
      homologues in other bacteria are also periplasmic IroE-type esterases of
      siderophores.

PMID- 16000727
TI  - Shifts from glucose to certain secondary carbon-sources result in activation of
      the extracytoplasmic function sigma factor sigmaE in Salmonella enterica serovar
      Typhimurium.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) elicits the starvation
      stress response (SSR) due to starvation for an essential nutrient, e.g. a
      carbon/energy source (C-source). As part of the SSR, the alternative sigma factor
      sigma(E) is activated and induced. The authors suspect that this activation is,
      in part, triggered by changes in the S. Typhimurium cell envelope occurring
      during the adaptation from growth to carbon/energy starvation (C-starvation), and
      resulting in an increased need for sigma(E)-regulated factors involved in the
      proper folding and assembly of newly synthesized proteins destined for this
      extracytoplasmic compartment. This led to the hypothesis that a sigma(E)
      activation signal might arise during C-source shifts that cause the induction of
      proteins localized to the extracytoplasmic compartment, i.e. the outer membrane
      or periplasm, of the cell. To test this hypothesis, cultures were grown in
      minimal medium containing enough glucose to reach mid-exponential-phase, plus a
      non-limiting amount of a secondary 'less-preferred' but utilizable carbon/energy
      source. The sigma(E) activity was then monitored using plasmids carrying rpoEP1-
      and rpoEP2-lacZ transcriptional fusions, which exhibit sigma(E)-independent and 
      dependent lacZ expression, respectively. The secondary C-sources maltose,
      succinate and citrate, which have extracytoplasmic components involved in their
      utilization (e.g. LamB), resulted in a discernible diauxic lag period and a
      sustained increase in sigma(E) activity. Growth transition from glucose to other
      utilizable phosphotransferase (PTS) and non-PTS C-sources, such as trehalose,
      mannose, mannitol, fructose, glycerol, d-galactose or l-arabinose, did not cause
      a discernible diauxic lag period or a sustained increase in sigma(E) activity.
      Interestingly, a shift from glucose to melibiose, which does not use an
      extracytoplasmic-localized protein for uptake, did cause an observable diauxic
      lag period but did not result in a sustained increase in sigma(E) activity. In
      addition, overexpression of LamB from an arabinose-inducible promoter leads to a
      significant increase in sigma(E) activity in the absence of a glucose to maltose
      shift or C-starvation. Furthermore, a DeltalamB : : Omega-Km(r) mutant, lacking
      the LamB maltoporin, exhibited an approximately twofold reduction in the
      sustained sigma(E) activity observed during a glucose to maltose shift, again
      supporting the hypothesis. Interestingly, the LamB protein lacks the typical Y-X
      F terminal tripeptide of the OmpC-like peptides that activate DegS protease
      activity leading to sigma(E) activation. It does, however, possess a terminal
      pentapeptide (Q-M-E-I-W-W) that may function as a ligand for a putative class II
      PDZ-binding site. The authors therefore propose that the sigma(E) regulon of S.
      Typhimurium not only is induced in response to deleterious environmental
      conditions, but also plays a role in the adaptation of cells to new growth
      conditions that necessitate changes in the extracytoplasmic compartment of the
      cell, which may involve alternative signal recognition and activation pathways
      that are independent of DegS.

PMID- 16000728
TI  - Hyperglycosylation of glycopeptidolipid of Mycobacterium smegmatis under nutrient
      starvation: structural studies.
AB  - The presence of a polar species of glycopeptidolipid (GPL) in carbon-starved
      Mycobacterium smegmatis has been reported previously. In this study, the complete
      structure of this GPL is established with the help of MALDI-TOF (matrix assisted
      laser desorption/ionization time of flight) and ESI (electrospray ionization) 
      MS, (13)C-SEFT (spin echo Fourier transform) -NMR spectroscopy, and HPLC
      analysis. In the molecule, two units of a 3,4-di-O-methyl derivative of rhamnose
      are attached to l-alaninol via a 1-->2 linkage. Various methyl derivatives of
      rhamnose and 6-deoxytalose were synthesized as standards to establish this
      structure. The accumulation of this polar GPL in M. smegmatis is sigB dependent,
      as a SigB-overproducing strain of M. smegmatis shows the presence of this spot in
      the exponential phase, and a sigB-knockout strain of M. smegmatis does not show
      the presence of any polar GPLs.

PMID- 16000729
TI  - Identification and targeted disruption of the gene encoding the main 3
      ketosteroid dehydrogenase in Mycobacterium smegmatis.
AB  - The catabolic potential for sterol degradation of fast-growing mycobacteria is
      well known. However, no genes or enzymes responsible for the steroid degradation
      process have been identified as yet in these species. One of the key enzymes
      required for degradation of the steroid ring structure is 3-ketosteroid Delta(1)
      dehydrogenase (KsdD). The recent annotation of the Mycobacterium smegmatis genome
      (TIGR database) revealed six KsdD homologues. Targeted disruption of the
      MSMEG5898 (ksdD-1) gene, but not the MSMEG4855 (ksdD-2) gene, resulted in partial
      inactivation of the cholesterol degradation pathway and accumulation of the
      intermediate 4-androstene-3,17-dione. This effect was reversible by the
      introduction of the wild-type ksdD-1 gene into M. smegmatis DeltaksdD-1 or
      overexpression of ksdD-2. The data indicate that KsdD1 is the main KsdD in M.
      smegmatis, but that KsdD2 is able to perform the cholesterol degradation process
      when overproduced.

PMID- 16000730
TI  - Porins limit the intracellular persistence of Mycobacterium smegmatis.
AB  - The genus Mycobacterium comprises highly pathogenic as well as opportunistic or
      apathogenic species exhibiting a great variability with respect to their ability
      to persist or multiply within monocytic host cells. The impact of the
      permeability of the mycobacterial outer membrane on intracellular persistence was
      studied. For this purpose, a Mycobacterium smegmatis mutant with a deletion of
      the major porin gene mspA and a second mutant lacking mspA and the homologous
      porin gene mspC were used. Deletion of mspA together with mspC significantly
      enhanced intracellular persistence in murine bone marrow macrophages, the mouse
      macrophage cell line J774A.1 and Acanthamoeba castellanii. Complementation of
      mspA in the porin mutant strains resulted in restoration of the wild-type
      phenotype with respect to intracellular persistence. This is the first report to
      show that the deletion of porins of mycobacteria results in improved persistence
      in eukaryotic cells, demonstrating that the intracellular persistence of M.
      smegmatis depends upon the permeability of the outer membrane.

PMID- 16000732
TI  - Two functional FAS-I type fatty acid synthases in Corynebacterium glutamicum.
AB  - The lipid-rich Corynebacterianeae, to which Corynebacterium glutamicum and
      Mycobacterium species belong, produce both fatty acids and mycolic acids.
      Compared with most other bacteria, C. glutamicum possesses two fatty acid
      synthases, encoded by fasA (8907 kb; FAS-IA) and fasB (8988 kb; FAS-IB). Here, it
      was shown by mutational analyses that fasA is essential but fasB is not. However,
      in a fasA background, the fasB mutation results in a slightly reduced growth
      yield, l-glutamate production is increased, and comparative lipid analysis
      suggests that in vivo FAS-IB is active primarily to supply palmitate. Transcript
      quantifications revealed that the fasB transcript contributes 32 % to both fas
      transcripts during growth on glucose, affirmative for fasB expression, and that
      fasB is subordinate to fasA. The fasA transcript is downregulated by 8.3-fold
      during growth on acetate as compared with glucose. The lipid analyses also
      demonstrate that cells grown on propionate produce a number of uneven fatty acids
      (e.g. 15 : 0, 17 : 0, 17 : 1), which are not present in cells grown on glucose or
      acetate, suggesting that fatty acid synthase in vivo may also use propionyl-CoA
      as the priming unit in fatty acid synthesis. The fatty acid auxotrophic fasAB
      double mutant was used to determine the suggested incorporation of fatty acids
      into mycolic acids. Supplementation of this mutant with uniformly labelled
      [(13)C]oleate and analysis of isolated mycolic acids confirmed that mature
      mycolic acids in the mutant consist exclusively of two fused [(13)C]oleate
      molecules. In addition to an altered phospholipid profile, the fasB mutant also
      exhibits differences in its mycolic acid profile. Taken together, the results
      show that although FAS-IA is the most relevant fatty acid synthase of C.
      glutamicum and FAS-IB is supplementary, both synthases are necessary to produce
      the characteristic lipid environment of this organism.

PMID- 16000731
TI  - Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed
      by proteomics.
AB  - Membrane-associated proteins of Mycobacterium tuberculosis offer a challenge, as
      well as an opportunity, in the quest for better therapeutic and prophylactic
      interventions against tuberculosis. The authors have previously reported that
      extraction with the detergent Triton X-114 (TX-114) is a useful step in proteomic
      analysis of mycobacterial cell membranes, and detergent-soluble membrane proteins
      of mycobacteria are potent stimulators of human T cells. In this study 1-D and 2
      D gel electrophoresis-based protocols were used for the analysis of proteins in
      the TX-114 extract of M. tuberculosis membranes. Peptide mass mapping (using
      MALDI-TOF-MS, matrix assisted laser desorption/ionization time of flight mass
      spectrometry) of 116 samples led to the identification of 105 proteins, 9 of
      which were new to the M. tuberculosis proteome. Functional orthologues of 73 of
      these proteins were also present in Mycobacterium leprae, suggesting their
      relative importance. Bioinformatics predicted that as many as 73% of the proteins
      had a hydrophobic disposition. 1-D gel electrophoresis revealed more
      hydrophobic/transmembrane and basic proteins than 2-D gel electrophoresis.
      Identified proteins fell into the following major categories: protein synthesis,
      cell wall biogenesis/architecture and conserved hypotheticals/unknowns. To
      identify immunodominant proteins of the detergent phase (DP), 14 low-molecular
      mass fractions prepared by continuous-elution gel electrophoresis were subjected
      to T cell activation assays using blood samples from BCG-vaccinated healthy
      donors from a tuberculosis endemic area. Analysis of the responses (cell
      proliferation and IFN-gamma production) showed that the immunodominance of
      certain DP fractions was most probably due to ribosomal proteins, which is
      consistent with both their specificity for mycobacteria and their abundance.
      Other membrane-associated proteins, including transmembrane proteins/lipoproteins
      and ESAT-6, did not appear to contribute significantly to the observed T cell
      responses.

PMID- 16000733
TI  - PorH, a new channel-forming protein present in the cell wall of Corynebacterium
      efficiens and Corynebacterium callunae.
AB  - Corynebacterium callunae and Corynebacterium efficiens are close relatives of the
      glutamate-producing mycolata species Corynebacterium glutamicum. The properties
      of the pore-forming proteins, extracted by organic solvents, were studied. The
      cell extracts contained channel-forming proteins that formed ion-permeable
      channels with a single-channel conductance of about 2 to 3 nS in 1 M KCl in a
      lipid bilayer assay. The corresponding proteins from both corynebacteria were
      purified to homogeneity and were named PorH(C.call) and PorH(C.eff).
      Electrophysiological studies of the channels suggested that they are wide and
      water-filled. Channels formed by PorH(C.call) are cation-selective, whereas
      PorH(C.eff) forms slightly anion-selective channels. Both proteins were partially
      sequenced. A multiple sequence alignment search within the known chromosome of C.
      efficiens demonstrated that it contains a gene that fits the partial amino acid
      sequence of PorH(C.eff). PorH(C.call) shows high homology to PorH(C.eff).
      PorH(C.eff) is encoded in the bacterial chromosome by a gene that is localized
      within the vicinity of the porA gene of C. efficiens. PorH(C.eff) has no signal
      sequence at the N terminus, which means that it is not exported by the Sec
      secretion pathway. The structure of PorH in the cell wall of the corynebacteria
      is discussed.

PMID- 16000734
TI  - High-level, inducible gene expression in Lactobacillus sakei and Lactobacillus
      plantarum using versatile expression vectors.
AB  - Vectors have been developed for inducible gene expression in Lactobacillus sakei
      and Lactobacillus plantarum in which expression of the gene of interest is driven
      by strong, regulated promoters from bacteriocin operons found in L. sakei
      strains. The activity of these promoters is controlled via a two-component signal
      transduction system, which responds to an externally added peptide pheromone. The
      vectors have a modular design, permitting easy exchange of all essential
      elements: the inducible promoter, the cognate regulatory system, the gene of
      interest, the antibiotic resistance marker and the replicon. Various variants of
      these so-called 'pSIP' vectors were constructed and tested, differing in terms of
      the bacteriocin regulon from which the regulatory elements were derived (sakacin
      A or sakacin P), the regulated promoter selected from these regulons, and the
      replicon (derived from p256 or pSH71). Using beta-glucuronidase (GusA) and
      aminopeptidase N (PepN) as reporters, it was shown that the best vectors
      permitted inducible, pheromone-dose-dependent gene expression at very high
      levels, while displaying moderate basal activities when not induced. The most
      effective set-up was obtained using a vector containing the pSH71 replicon, the
      orfX promoter from the sakacin P regulon, and the cognate regulatory genes, in a
      L. sakei host. GusA levels obtained with this set-up were approximately ten times
      higher than the levels obtained with prototype pSIP versions, whereas PepN levels
      amounted to almost 50% of total cellular protein.

PMID- 16000735
TI  - Campylobacter jejuni inhibits the absorptive transport functions of Caco-2 cells
      and disrupts cellular tight junctions.
AB  - Caco-2 cells are models of absorptive enterocytes. The net transport of fluid
      from apical to basolateral surfaces results in 'domes' forming in differentiated
      monolayers. Here, the effect of Campylobacter jejuni on this process has been
      examined. C. jejuni caused no changes in short-circuit current upon infection of
      Caco-2 cell monolayers in Ussing chambers. Thus, no active secretory events could
      be demonstrated using this model. It was therefore hypothesized that C. jejuni
      could inhibit the absorptive function of enterocytes and that this may contribute
      to diarrhoeal disease. C. jejuni infection of fluid-transporting ('doming') Caco
      2 cells resulted in a significant reduction in dome number, which correlated with
      a decrease in tight junction integrity in infected monolayers, when measured as
      transepithelial electrical resistance. Defined mutants of C. jejuni also reduced
      dome numbers in infected monolayers. C. jejuni also altered the distribution of
      the tight junction protein occludin within cell monolayers. The addition to
      monolayers of extracellular gentamicin prevented these changes, indicating the
      contribution of extracellular bacteria to this process. Thus, tight junction
      integrity is required for fluid transport in Caco-2 cell monolayers as leaky
      tight junctions cannot maintain support of transported fluid at the basolateral
      surface of infected cell monolayers. Inhibition of absorptive cell function,
      changes in epithelial resistance and rearrangement of tight junctional proteins
      such as occludin represent a potential diarrhoeal mechanism of C. jejuni.

PMID- 16000736
TI  - Atomic force microscopy study on specificity and non-specificity of interaction
      forces between Enterococcus faecalis cells with and without aggregation
      substance.
AB  - Enterococcus faecalis is one of the leading causes of hospital-acquired
      infections, and indwelling medical devices are especially prone to infection. E.
      faecalis expressing aggregation substance (Agg) adheres to biomaterial surfaces
      by means of positive cooperativity, i.e. the ability of one adhering organism to
      stimulate adhesion of other organisms in its immediate vicinity. In this study,
      atomic force microscopy (AFM) was used to measure the specificity and non
      specificity of interaction forces between E. faecalis cells with and without Agg.
      Bacteria were attached to a substratum surface and a tip-less cantilever. Two E.
      faecalis strains expressing different forms of Agg showed nearly twofold higher
      interaction forces between bacterial cells than a strain lacking Agg [adhesive
      force (F(adh)), -1.3 nN]. The strong interaction forces between the strains with
      Agg were reduced after adsorption of antibodies against Agg from -2.6 and -2.3 nN
      to -1.2 and -1.3 nN, respectively. This suggests that the non-specific
      interaction force between the enterococci amounts to approximately 1.2 nN, while
      the specific force component is only twofold stronger. Comparison of the results
      of the AFM interaction forces with the positive cooperativity after adhesion to a
      biomaterial in a parallel-plate flow chamber showed that in the absence of strong
      interaction forces between the cells, positive cooperativity was also absent. In
      conclusion, this is believed to be the first time that the influence of specific
      antibodies on interaction forces between E. faecalis cells has been demonstrated
      by AFM, thereby experimentally distinguishing between specific and non-specific
      force components.

PMID- 16000737
TI  - Bap-dependent biofilm formation by pathogenic species of Staphylococcus: evidence
      of horizontal gene transfer?
AB  - The biofilm-associated protein (Bap) is a surface protein implicated in biofilm
      formation by Staphylococcus aureus isolated from chronic mastitis infections. The
      bap gene is carried in a putative composite transposon inserted in SaPIbov2, a
      mobile staphylococcal pathogenicity island. In this study, bap orthologue genes
      from several staphylococcal species, including Staphylococcus epidermidis,
      Staphylococcus chromogenes, Staphylococcus xylosus, Staphylococcus simulans and
      Staphylococcus hyicus, were identified, cloned and sequenced. Sequence analysis
      comparison of the bap gene from these species revealed a very high sequence
      similarity, suggesting the horizontal gene transfer of SaPIbov2 amongst them.
      However, sequence analyses of the flanking region revealed that the bap gene of
      these species was not contained in the SaPIbov2 pathogenicity island. Although
      they did not contain the icaADBC operon, all the coagulase-negative
      staphylococcal isolates harbouring bap were strong biofilm producers. Disruption
      of the bap gene in S. epidermidis abolished its capacity to form a biofilm,
      whereas heterologous complementation of a biofilm-negative strain of S. aureus
      with the Bap protein from S. epidermidis bestowed the capacity to form a biofilm
      on a polystyrene surface. Altogether, these results demonstrate that Bap
      orthologues from coagulase-negative staphylococci induce an alternative mechanism
      of biofilm formation that is independent of the PIA/PNAG exopolysaccharide.

PMID- 16000738
TI  - A surface-exposed DraD protein of uropathogenic Escherichia coli bearing Dr
      fimbriae may be expressed and secreted independently from DraC usher and DraE
      adhesin.
AB  - The dra gene cluster, expressed by uropathogenic Escherichia coli strains,
      determines bacterial attachment and invasion. The Dr fimbrial structures formed
      at the bacterial cell surface are composed of DraE subunits. The Dr fimbriae
      coding cluster contains six open reading frames--draA, draB, draC, draD, draP and
      draE--among which the draE gene encodes the structural fimbrial subunit DraE.
      Very little is known about E. coli surface expression of the draD gene product.
      The expression of DraD and its role in the biogenesis of Dr fimbriae were
      determined by constructing mutants in the dra operon and by immunoblot and
      immunofluorescence experiments. In this study, DraD was found to be a surface
      exposed protein. The expression of DraD was independent of the DraC usher and
      DraE fimbrial subunits. Polymerization of DraE fimbrial subunits into fimbrial
      structures did not require expression of the DraD protein.

PMID- 16000739
TI  - Escherichia coli tol and rcs genes participate in the complex network affecting
      curli synthesis.
AB  - Curli are necessary for the adherence of Escherichia coli to surfaces, and to
      each other, during biofilm formation, and the csgBA and csgDEFG operons are both
      required for their synthesis. A recent survey of gene expression in Pseudomonas
      aeruginosa biofilms has identified tolA as a gene activated in biofilms. The tol
      genes play a fundamental role in maintaining the outer-membrane integrity of Gram
      negative bacteria. RcsC, the sensor of the RcsBCD phosphorelay, is involved,
      together with RcsA, in colanic acid capsule synthesis, and also modulates the
      expression of tolQRA and csgDEFG. In addition, the RcsBCD phosphorelay is
      activated in tol mutants or when Tol proteins are overexpressed. These results
      led the authors to investigate the role of the tol genes in biofilm formation in
      laboratory and clinical isolates of E. coli. It was shown that the adherence of
      cells was lowered in the tol mutants. This could be the result of a drastic
      decrease in the expression of the csgBA operon, even though the expression of
      csgDEFG was slightly increased under such conditions. It was also shown that the
      Rcs system negatively controls the expression of the two csg operons in an RcsA
      dependent manner. In the tol mutants, activation of csgDEFG occurred via OmpR and
      was dominant upon repression by RcsB and RcsA, while these two regulatory
      proteins repressed csgBA through a dominant effect on the activator protein CsgD,
      thus affecting curli synthesis. The results demonstrate that the Rcs system,
      previously known to control the synthesis of the capsule and the flagella, is an
      additional component involved in the regulation of curli. Furthermore, it is
      shown that the defect in cell motility observed in the tol mutants depends on
      RcsB and RcsA.

PMID- 16000741
TI  - Combined effect of high-pressure treatments and bacteriocin-producing lactic acid
      bacteria on inactivation of Escherichia coli O157:H7 in raw-milk cheese.
AB  - The effect of high-pressure (HP) treatments combined with bacteriocins of lactic
      acid bacteria (LAB) produced in situ on the survival of Escherichia coli O157:H7
      in cheese was investigated. Cheeses were manufactured from raw milk inoculated
      with E. coli O157:H7 at approximately 10(5) CFU/ml. Seven different bacteriocin
      producing LAB were added at approximately 10(6) CFU/ml as adjuncts to the
      starter. Cheeses were pressurized on day 2 or 50 at 300 MPa for 10 min or 500 MPa
      for 5 min, at 10 degrees C in both cases. After 60 days, E. coli O157:H7 counts
      in cheeses manufactured without bacteriocin-producing LAB and not pressurized
      were 5.1 log CFU/g. A higher inactivation of E. coli O157:H7 was achieved in
      cheeses without bacteriocin-producing LAB when 300 MPa was applied on day 50 (3.8
      log-unit reduction) than if applied on day 2 (1.3-log-unit reduction).
      Application of 500 MPa eliminated E. coli O157:H7 in 60-day-old cheeses. Cheeses
      made with bacteriocin-producing LAB and not pressurized showed a slight reduction
      of the pathogen. Pressurization at 300 MPa on day 2 and addition of lacticin 481
      , nisin A-, bacteriocin TAB 57-, or enterocin AS-48-producing LAB were
      synergistic and reduced E. coli O157:H7 counts to levels below 2 log units in 60
      day-old cheeses. Pressurization at 300 MPa on day 50 and addition of nisin A-,
      bacteriocin TAB 57-, enterocin I-, or enterocin AS-48-producing LAB completely
      inactivated E. coli O157:H7 in 60-day-old cheeses. The application of reduced
      pressures combined with bacteriocin-producing LAB is a feasible procedure to
      improve cheese safety.

PMID- 16000740
TI  - OusB, a broad-specificity ABC-type transporter from Erwinia chrysanthemi,
      mediates uptake of glycine betaine and choline with a high affinity.
AB  - The ability of Erwinia chrysanthemi to cope with environments of elevated
      osmolality is due in part to the transport and accumulation of osmoprotectants.
      In this study we have identified a high-affinity glycine betaine and choline
      transport system in E. chrysanthemi. By using a pool of Tn5-B21 ousA mutants, we
      isolated a mutant that could grow in the presence of a toxic analogue of glycine
      betaine (benzyl-glycine betaine) at high osmolalities. This mutant was impaired
      in its ability to transport all effective osmoprotectants in E. chrysanthemi. The
      DNA sequence of the regions flanking the transposon insertion site revealed three
      chromosomal genes (ousVWX) that encode components of an ABC-type transporter
      (OusB): OusV (ATPase), OusW (permease), and OusX (periplasmic binding protein).
      The OusB components showed a significant degree of sequence identity to
      components of ProU from Salmonella enterica serovar Typhimurium and Escherichia
      coli. OusB was found to restore the uptake of glycine betaine and choline through
      functional complementation of an E. coli mutant defective in both ProU and ProP
      osmoprotectant uptake systems. Competition experiments demonstrated that choline,
      dimethylsulfoniacetate, dimethylsulfoniopropionate, and ectoine were effective
      competitors for OusB-mediated betaine transport but that carnitine, pipecolate,
      and proline were not effective. In addition, the analysis of single and double
      mutants showed that OusA and OusB were the only osmoprotectant transporters
      operating in E. chrysanthemi.

PMID- 16000742
TI  - Bovine feces from animals with gastrointestinal infections are a source of
      serologically diverse atypical enteropathogenic Escherichia coli and Shiga toxin
      producing E. coli strains that commonly possess intimin.
AB  - Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC)
      cells were isolated from 191 fecal samples from cattle with gastrointestinal
      infections (diagnostic samples) collected in New South Wales, Australia. By using
      a multiplex PCR, E. coli cells possessing combinations of stx1, stx2, eae, and
      ehxA were detected by a combination of direct culture and enrichment in E. coli
      (EC) (modified) broth followed by plating on vancomycin-cefixime-cefsulodin blood
      (BVCC) agar for the presence of enterohemolytic colonies and on sorbitol
      MacConkey agar for the presence of non-sorbitol-fermenting colonies. The high
      prevalence of the intimin gene eae was a feature of the STEC (35 [29.2%] of 120
      isolates) and contrasted with the low prevalence (9 [0.5%] of 1,692 fecal samples
      possessed STEC with eae) of this gene among STEC recovered during extensive
      sampling of feces from healthy slaughter-age cattle in Australia (M. Hornitzky,
      B. A. Vanselow, K. Walker, K. A. Bettelheim, B. Corney, P. Gill, G. Bailey, and
      S. P. Djordjevic, Appl. Environ. Microbiol. 68:6439-6445, 2002). Forty-seven STEC
      serotypes were identified, including O5:H-, O8:H19, O26:H-, O26:H11, O113:H21,
      O157:H7, O157:H- and Ont:H- which are known to cause severe disease in humans and
      23 previously unreported STEC serotypes. Serotypes Ont:H- and O113:H21
      represented the two most frequently isolated STEC isolates and were cultured from
      nine (4.7%) and seven (3.7%) animals, respectively. Fifteen eae-positive E. coli
      serotypes, considered to represent atypical EPEC, were identified, with O111:H-
      representing the most prevalent. Using both techniques, STEC cells were cultured
      from 69 (36.1%) samples and EPEC cells were cultured from 30 (15.7%) samples,
      including 9 (4.7%) samples which yielded both STEC and EPEC. Culture on BVCC agar
      following enrichment in EC (modified) broth was the most successful method for
      the isolation of STEC (24.1% of samples), and direct culture on BVCC agar was the
      most successful method for the isolation of EPEC (14.1% samples). These studies
      show that diarrheagenic calves and cattle represent important reservoirs of eae
      positive E. coli.

PMID- 16000744
TI  - Similarities and specificities of fungal keratinolytic proteases: comparison of
      keratinases of Paecilomyces marquandii and Doratomyces microsporus to some known
      proteases.
AB  - Based on previous screening for keratinolytic nonpathogenic fungi, Paecilomyces
      marquandii and Doratomyces microsporus were selected for production of potent
      keratinases. The enzymes were purified and their main biochemical characteristics
      were determined (molecular masses, optimal temperature and pH for keratinolytic
      activity, N-terminal amino acid sequences). Studies of substrate specificity
      revealed that skin constituents, such as the stratum corneum, and appendages such
      as nail but not hair, feather, and wool were efficiently hydrolyzed by the P.
      marquandii keratinase and about 40% less by the D. microsporus keratinase.
      Hydrolysis of keratin could be increased by the presence of reducing agents. The
      catalytic properties of the keratinases were studied and compared to those of
      some known commercial proteases. The profile of the oxidized insulin B-chain
      digestion revealed that both keratinases, like proteinase K but not subtilisin,
      trypsin, or elastase, possess broad cleavage specificity with a preference for
      aromatic and nonpolar amino acid residues at the P-1 position. Kinetic studies
      were performed on a synthetic substrate, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide.
      The keratinase of P. marquandii exhibited the lowest Km among microbial
      keratinases reported in the literature, and its catalytic efficiency was high in
      comparison to that of D. microsporus keratinase and proteinase K. All three
      keratinolytic enzymes, the keratinases of P. marquandii and D. microsporus as
      well as proteinase K, were significantly more active on keratin than subtilisin,
      trypsin, elastase, chymotrypsin, or collagenase.

PMID- 16000743
TI  - Stable isotope fractionation of tetrachloroethene during reductive dechlorination
      by Sulfurospirillum multivorans and Desulfitobacterium sp. strain PCE-S and
      abiotic reactions with cyanocobalamin.
AB  - Carbon stable isotope fractionation of tetrachloroethene (PCE) during reductive
      dechlorination by whole cells and crude extracts of Sulfurospirillum multivorans
      and Desulfitobacterium sp. strain PCE-S and the abiotic reaction with
      cyanocobalamin (vitamin B12) was studied. Fractionation was largest during the
      reaction with cyanocobalamin with alphaC = 1.0132. Stable isotope fractionation
      was lower but still in a similar order of magnitude for Desulfitobacterium sp.
      PCE-S (alphaC = 1.0052 to 1.0098). The isotope fractionation of PCE during
      dehalogenation by S. multivorans was lower by 1 order of magnitude (alphaC =
      1.00042 to 1.0017). Additionally, an increase in isotope fractionation was
      observed with a decrease in cell integrity for both strains. For
      Desulfitobacterium sp. strain PCE-S, the carbon stable isotope fractionation
      factors were 1.0052 and 1.0089 for growing cells and crude extracts,
      respectively. For S. multivorans, alphaC values were 1.00042, 1.00097, and 1.0017
      for growing cells, crude extracts, and the purified PCE reductive dehalogenase,
      respectively. For the field application of stable isotope fractionation, care is
      needed as fractionation may vary by more than an order of magnitude depending on
      the bacteria present, responsible for degradation.

PMID- 16000745
TI  - Alternative luciferase for monitoring bacterial cells under adverse conditions.
AB  - The availability of cloned luciferase genes from fireflies (luc) and from
      bacteria (luxAB) has led to the widespread use of bioluminescence as a reporter
      to measure cell viability and gene expression. The most commonly occurring
      bioluminescence system in nature is the deep-sea imidazolopyrazine
      bioluminescence system. Coelenterazine is an imidazolopyrazine derivative which,
      when oxidized by an appropriate luciferase enzyme, produces carbon dioxide,
      coelenteramide, and light. The luciferase from the marine copepod Gaussia
      princeps (Gluc) has recently been cloned. We expressed the Gluc gene in
      Mycobacterium smegmatis using a shuttle vector and compared its performance with
      that of an existing luxAB reporter. In contrast to luxAB, the Gluc luciferase
      retained its luminescence output in the stationary phase of growth and exhibited
      enhanced stability during exposure to low pH, hydrogen peroxide, and high
      temperature. The work presented here demonstrated the utility of the copepod
      luciferase bioluminescent reporter as an alternative to bacterial luciferase,
      particularly for monitoring responses to environmental stress stimuli.

PMID- 16000746
TI  - Quantitative detection of Legionella pneumophila in water samples by
      immunomagnetic purification and real-time PCR amplification of the dotA gene.
AB  - A new real-time PCR assay was developed and validated in combination with an
      immunomagnetic separation system for the quantitative determination of Legionella
      pneumophila in water samples. Primers that amplify simultaneously an 80-bp
      fragment of the dotA gene from L. pneumophila and a recombinant fragment
      including a specific sequence of the gyrB gene from Aeromonas hydrophila, added
      as an internal positive control, were used. The specificity, limit of detection,
      limit of quantification, repetitivity, reproducibility, and accuracy of the
      method were calculated, and the values obtained confirmed the applicability of
      the method for the quantitative detection of L. pneumophila. Moreover, the
      efficiency of immunomagnetic separation in the recovery of L. pneumophila from
      different kinds of water was evaluated. The recovery rates decreased as the water
      contamination increased (ranging from 59.9% for distilled water to 36% for
      cooling tower water), and the reproducibility also decreased in parallel to water
      complexity. The feasibility of the method was evaluated by cell culture and real
      time PCR analysis of 60 samples in parallel. All the samples found to be positive
      by cell culture were also positive by real-time PCR, while only eight samples
      were found to be positive only by PCR. Finally, the correlation of both methods
      showed that the number of cells calculated by PCR was 20-fold higher than the
      culture values. In conclusion, the real-time PCR method combined with
      immunomagnetic separation provides a sensitive, specific, and accurate method for
      the rapid quantification of L. pneumophila in water samples. However, the
      recovery efficiency of immunomagnetic separation should be considered in complex
      samples.

PMID- 16000747
TI  - Functional identification of novel genes involved in the glutathione-independent
      gentisate pathway in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum used gentisate and 3-hydroxybenzoate as its sole
      carbon and energy source for growth. By genome-wide data mining, a gene cluster
      designated ncg12918-ncg12923 was proposed to encode putative proteins involved in
      gentisate/3-hydroxybenzoate pathway. Genes encoding gentisate 1,2-dioxygenase
      (ncg12920) and fumarylpyruvate hydrolase (ncg12919) were identified by cloning
      and expression of each gene in Escherichia coli. The gene of ncg12918 encoding a
      hypothetical protein (Ncg12918) was proved to be essential for gentisate-3
      hydroxybenzoate assimilation. Mutant strain RES167Deltancg12918 lost the ability
      to grow on gentisate or 3-hydroxybenzoate, but this ability could be restored in
      C. glutamicum upon the complementation with pXMJ19-ncg12918. Cloning and
      expression of this ncg12918 gene in E. coli showed that Ncg12918 is a glutathione
      independent maleylpyruvate isomerase. Upstream of ncg12920, the genes ncg12921
      ncg12923 were located, which were essential for gentisate and/or 3
      hydroxybenzoate catabolism. The Ncg12921 was able to up-regulate gentisate 1,2
      dioxygenase, maleylpyruvate isomerase, and fumarylpyruvate hydrolase activities.
      The genes ncg12922 and ncg12923 were deduced to encode a gentisate transporter
      protein and a 3-hydroxybenzoate hydroxylase, respectively, and were essential for
      gentisate or 3-hydroxybenzoate assimilation. Based on the results obtained in
      this study, a GSH-independent gentisate pathway was proposed, and genes involved
      in this pathway were identified.

PMID- 16000748
TI  - Polyketide synthase gene responsible for citrinin biosynthesis in Monascus
      purpureus.
AB  - Citrinin produced by Aspergillus, Penicillium, and Monascus species is a
      polyketide compound that has nephrotoxic activity in mammals and is bactericidal
      toward gram-positive bacteria. To avoid the risk of citrinin contamination in
      other fermentation products produced by Monascus purpureus, knowledge of the
      citrinin biosynthetic genes is needed so that citrinin-nonproducing strains can
      be generated. We cloned a polyketide synthase (PKS) gene from M. purpureus with
      degenerate primers designed to amplify the conserved region of a ketosynthase
      domain of a fungal PKS. A 13-kb genomic DNA fragment was identified that
      contained a full-length PKS gene (pksCT) of 7,838 bp with a single 56-bp intron.
      pksCT encodes a 2,593-amino-acid protein that contains putative domains for
      ketosynthase, acyltransferase, acyl carrier protein (ACP), and a rare
      methyltransferase. There was no obvious thioesterase domain, which usually is
      downstream of the ACP domain in multi-aromatic-ring PKSs. pksCT transcription was
      correlated with citrinin production, suggesting that the pksCT gene product was
      involved in citrinin biosynthesis. Homologous recombination between the wild-type
      allele and a truncated disruption construct resulted in a pksCT-disrupted strain
      of M. purpureus. The disruptant did not produce citrinin, but a pksCT revertant
      generated by successive endogenous recombination events in the pksCT disruptant
      restored citrinin production, indicating that pksCT encoded the PKS responsible
      for citrinin biosynthesis in M. purpureus.

PMID- 16000749
TI  - Anaerobic n-alkane metabolism by a sulfate-reducing bacterium, Desulfatibacillum
      aliphaticivorans strain CV2803T.
AB  - The alkane-degrading, sulfate-reducing bacterium Desulfatibacillum
      aliphaticivorans strain CV2803T, recently isolated from marine sediments, was
      investigated for n-alkane metabolism. The total cellular fatty acids of this
      strain had predominantly odd numbers of carbon atoms (C odd) when the strain was
      grown on a C-odd alkane (pentadecane) and even numbers of carbon atoms (C even)
      when it was grown on a C-even alkane (hexadecane). Detailed analyses of those
      fatty acids by gas chromatography/mass spectrometry allowed us to identify
      saturated 2-, 4-, 6-, and 8-methyl- and monounsaturated 6-methyl-branched fatty
      acids, with chain lengths that specifically correlated with those of the alkane.
      Growth of D. aliphaticivorans on perdeuterated hexadecane demonstrated that those
      methyl-branched fatty acids were directly derived from the substrate. In
      addition, cultures on pentadecane and hexadecane produced (1
      methyltetradecyl)succinate and (1-methylpentadecyl)succinate, respectively. These
      results indicate that D. aliphaticivorans strain CV2803T oxidizes n-alkanes into
      fatty acids anaerobically, via the addition of fumarate at C-2. Based on our
      observations and on literature data, a pathway for anaerobic n-alkane metabolism
      by D. aliphaticivorans is proposed. This involves the transformation of the
      initial alkylsuccinate into a 4-methyl-branched fatty acid which, in addition to
      catabolic reactions, can alternatively undergo chain elongation and desaturation
      to form storage fatty acids.

PMID- 16000750
TI  - Enhancement of the efficiency of secretion of heterologous lipase in Escherichia
      coli by directed evolution of the ABC transporter system.
AB  - The ABC transporter (TliDEF) from Pseudomonas fluorescens SIK W1, which mediated
      the secretion of a thermostable lipase (TliA) into the extracellular space in
      Escherichia coli, was engineered using directed evolution (error-prone PCR) to
      improve its secretion efficiency. TliD mutants with increased secretion
      efficiency were identified by coexpressing the mutated tliD library with the wild
      type tliA lipase in E. coli and by screening the library with a tributyrin
      emulsified indicator plate assay and a microtiter plate-based assay. Four
      selected mutants from one round of error-prone PCR mutagenesis, T6, T8, T24, and
      T35, showed 3.2-, 2.6-, 2.9-, and 3.0-fold increases in the level of secretion of
      TliA lipase, respectively, but had almost the same level of expression of TliD in
      the membrane as the strain with the wild-type TliDEF transporter. These results
      indicated that the improved secretion of TliA lipase was mediated by the
      transporter mutations. Each mutant had a single amino acid change in the
      predicted cytoplasmic regions in the membrane domain of TliD, implying that the
      corresponding region of TliD was important for the improved and successful
      secretion of the target protein. We therefore concluded that the efficiency of
      secretion of a heterologous protein in E. coli can be enhanced by in vitro
      engineering of the ABC transporter.

PMID- 16000751
TI  - Transcriptional regulation and characterization of a novel beta
      fructofuranosidase-encoding gene from Bifidobacterium breve UCC2003.
AB  - An operon involved in fructooligosaccharide breakdown was identified in the
      genome of Bifidobacterium breve UCC2003. This 2.6-kb transcriptional unit was
      comprised of three genes that encoded a putative permease, a conserved
      hypothetical protein, and a beta-fructofuranosidase. Active transcription of the
      operon was observed when B. breve UCC2003 was grown on sucrose or Actilight,
      while transcription appeared to be repressed when the organism was grown on
      glucose, fructose, a combination of glucose and sucrose, or a combination of
      fructose and sucrose. The beta-fructofuranosidase encoded by this operon was
      purified and biochemically characterized. The optimum pH and temperature for
      catalytic activity were determined to be pH 6.0 and 37 degrees C, respectively,
      and there was a dependence on bivalent cations, particularly manganese. The Km
      and Vmax values for sucrose hydrolysis were determined to be 25 +/- 2 mM and 24
      +/- 3 micromol min(-1) mg(-1), respectively. Interestingly, the enzyme was shown
      to specifically catalyze cleavage of the beta(2-1) glycosidic bond between
      glucose and its neighboring fructose moiety in sucrose and other
      fructooligosaccharides with a relatively low degree of polymerization, and there
      was no detectable activity towards the beta(2-1) glycosidic bond between two
      fructose moieties within the same substrate. To our knowledge, such an enzymatic
      activity has not previously been described in bifidobacteria or other gram
      positive bacteria.

PMID- 16000752
TI  - Phylogenetic diversity and specificity of bacteria closely associated with
      Alexandrium spp. and other phytoplankton.
AB  - While several studies have suggested that bacterium-phytoplankton interactions
      have the potential to dramatically influence harmful algal bloom dynamics, little
      is known about how bacteria and phytoplankton communities interact at the species
      composition level. The objective of the current study was to determine whether
      there are specific associations between diverse phytoplankton and the bacteria
      that co-occur with them. We determined the phylogenetic diversity of bacterial
      assemblages associated with 10 Alexandrium strains and representatives of the
      major taxonomic groups of phytoplankton in the Gulf of Maine. For this analysis
      we chose xenic phytoplankton cultures that (i) represented a broad taxonomic
      range, (ii) represented a broad geographic range for Alexandrium spp. isolates,
      (iii) grew under similar cultivation conditions, (iv) had a minimal length of
      time since the original isolation, and (v) had been isolated from a vegetative
      phytoplankton cell. 16S rRNA gene fragments of most Bacteria were amplified from
      DNA extracted from cultures and were analyzed by denaturing gradient gel
      electrophoresis and sequencing. A greater number of bacterial species were shared
      by different Alexandrium cultures, regardless of the geographic origin, than by
      Alexandrium species and nontoxic phytoplankton from the Gulf of Maine. In
      particular, members of the Roseobacter clade showed a higher degree of
      association with Alexandrium than with other bacterial groups, and many sequences
      matched sequences reported to be associated with other toxic dinoflagellates.
      These results provide evidence for specificity in bacterium-phytoplankton
      associations.

PMID- 16000753
TI  - Description of toluene inhibition of methyl bromide biodegradation in seawater
      and isolation of a marine toluene oxidizer that degrades methyl bromide.
AB  - Methyl bromide (CH3Br) and methyl chloride (CH3Cl) are important precursors for
      destruction of stratospheric ozone, and oceanic uptake is an important component
      of the biogeochemical cycle of these methyl halides. In an effort to identify and
      characterize the organisms mediating halocarbon biodegradation, we surveyed the
      effect of potential cometabolic substrates on CH3Br biodegradation using a
      13CH3Br incubation technique. Toluene (160 to 200 nM) clearly inhibited CH3Br and
      CH3Cl degradation in seawater samples from the North Atlantic, North Pacific, and
      Southern Oceans. Furthermore, a marine bacterium able to co-oxidize CH3Br while
      growing on toluene was isolated from subtropical Western Atlantic seawater. The
      bacterium, Oxy6, was also able to oxidize o-xylene and the xylene monooxygenase
      (XMO) pathway intermediate 3-methylcatechol. Patterns of substrate oxidation,
      lack of acetylene inhibition, and the inability of the toluene 4-monooxygenase
      (T4MO)-containing bacterium Pseudomonas mendocina KR1 to degrade CH3Br ruled out
      participation of the T4MO pathway in Oxy6. Oxy6 also oxidized a variety of
      toluene (TOL) pathway intermediates such as benzyl alcohol, benzylaldehyde,
      benzoate, and catechol, but the inability of Pseudomonas putida mt-2 to degrade
      CH3Br suggested that the TOL pathway might not be responsible for CH3Br
      biodegradation. Molecular phylogenetic analysis identified Oxy6 to be a member of
      the family Sphingomonadaceae related to species within the Porphyrobacter genus.
      Although some Sphingomonadaceae can degrade a variety of xenobiotic compounds,
      this appears to be the first report of CH3Br degradation for this class of
      organism. The widespread inhibitory effect of toluene on natural seawater samples
      and the metabolic capabilities of Oxy6 indicate a possible link between aromatic
      hydrocarbon utilization and the biogeochemical cycle of methyl halides.

PMID- 16000754
TI  - Degradation of corn fiber by Clostridium cellulovorans cellulases and
      hemicellulases and contribution of scaffolding protein CbpA.
AB  - Clostridium cellulovorans, an anaerobic bacterium, degrades native substrates
      efficiently by producing an extracellular enzyme complex called the cellulosome.
      All cellulosomal enzyme subunits contain dockerin domains that can bind to
      hydrophobic domains termed cohesins which are repeated nine times in CbpA, the
      nonenzymatic scaffolding protein of C. cellulovorans cellulosomes. In this study,
      the synergistic interactions of cellulases (endoglucanase E, EngE; endoglucanase
      L, EngL) and hemicellulases (arabinofuranosidase A, ArfA; xylanase A, XynA) were
      determined on the degradation of corn fiber, a natural substrate containing
      mainly xylan, arabinan, and cellulose. The degradation by XynA and ArfA of
      cellulose/arabinoxylan was greater than that of corn fiber and resulted in 2.6
      fold and 1.4-fold increases in synergy, respectively. Synergistic effects were
      observed in increments in both simultaneous and sequential reactions with ArfA
      and XynA. These synergistic enzymes appear to represent potential rate-limiting
      enzymes for efficient hemicellulose degradation. When mini-cellulosomes were
      constructed from the cellulosomal enzymes (XynA and EngL) and mini-CbpA with
      cohesins 1 and 2 (mini-CbpA1&2) and mini-CbpA with cohesins 5 and 6 (mini
      CbpA5&6), higher activity was observed than that for the corresponding enzymes
      alone. Based on the degradation of different types of celluloses and
      hemicelluloses, the interaction between cellulosomal enzymes (XynA and EngL) and
      mini-CbpA displayed a diversity that suggests that dockerin-cohesin interaction
      from C. cellulovorans may be more selective than random.

PMID- 16000756
TI  - Effects of incubation temperature on growth and production of exopolysaccharides
      by an antarctic sea ice bacterium grown in batch culture.
AB  - The sea ice microbial community plays a key role in the productivity of the
      Southern Ocean. Exopolysaccharide (EPS) is a major component of the exopolymer
      secreted by many marine bacteria to enhance survival and is abundant in sea ice
      brine channels, but little is known about its function there. This study
      investigated the effects of temperature on EPS production in batch culture by
      CAM025, a marine bacterium isolated from sea ice sampled from the Southern Ocean.
      Previous studies have shown that CAM025 is a member of the genus
      Pseudoalteromonas and therefore belongs to a group found to be abundant in sea
      ice by culture-dependent and -independent techniques. Batch cultures were grown
      at -2 degrees C, 10 degrees C, and 20 degrees C, and cell number, optical
      density, pH, glucose concentration, and viscosity were monitored. The yield of
      EPS at -2 degrees C and 10 degrees C was 30 times higher than at 20 degrees C,
      which is the optimum growth temperature for many psychrotolerant strains. EPS may
      have a cryoprotective role in brine channels of sea ice, where extremes of high
      salinity and low temperature impose pressures on microbial growth and survival.
      The EPS produced at -2 degrees C and 10 degrees C had a higher uronic acid
      content than that produced at 20 degrees C. The availability of iron as a trace
      metal is of critical importance in the Southern Ocean, where it is known to limit
      primary production. EPS from strain CAM025 is polyanionic and may bind dissolved
      cations such at trace metals, and therefore the presence of bacterial EPS in the
      Antarctic marine environment may have important ecological implications.

PMID- 16000755
TI  - Role of porins in sensitivity of Escherichia coli to antibacterial activity of
      the lactoperoxidase enzyme system.
AB  - Lactoperoxidase is an enzyme that contributes to the antimicrobial defense in
      secretory fluids and that has attracted interest as a potential biopreservative
      for foods and other perishable products. Its antimicrobial activity is based on
      the formation of hypothiocyanate (OSCN-) from thiocyanate (SCN-), using H2O2 as
      an oxidant. To gain insight into the antibacterial mode of action of the
      lactoperoxidase enzyme system, we generated random transposon insertion mutations
      in Escherichia coli MG1655 and screened the resultant mutants for an altered
      tolerance of bacteriostatic concentrations of this enzyme system. Out of the ca.
      5,000 mutants screened, 4 showed significantly increased tolerance, and 2 of
      these had an insertion, one in the waaQ gene and one in the waaO gene, whose
      products are involved in the synthesis of the core oligosaccharide moiety of
      lipopolysaccharides. Besides producing truncated lipopolysaccharides and
      displaying hypersensitivity to novobiocin and sodium dodecyl sulfate (SDS), these
      mutants were also shown by urea-SDS-polyacrylamide gel electrophoresis analysis
      to have reduced amounts of porins in their outer membranes. Moreover, they showed
      a reduced degradation of p-nitrophenyl phosphate and an increased resistance to
      ampicillin, two indications of a decrease in outer membrane permeability for
      small hydrophilic solutes. Additionally, ompC and ompF knockout mutants displayed
      levels of tolerance to the lactoperoxidase system similar to those displayed by
      the waa mutants. These results suggest that mutations which reduce the porin
      mediated outer membrane permeability for small hydrophilic molecules lead to
      increased tolerance to the lactoperoxidase enzyme system because of a reduced
      uptake of OSCN-.

PMID- 16000757
TI  - Development of a simple and rapid fluorogenic procedure for identification of
      vibrionaceae family members.
AB  - We describe a simple colony overlay procedure for peptidases (COPP) for the rapid
      fluorogenic detection and quantification of Vibrionaceae from seawater,
      shellfish, sewage, and clinical samples. The assay detects phosphoglucose
      isomerase with a lysyl aminopeptidase activity that is produced by Vibrionaceae
      family members. Overnight cultures are overlaid for 10 min with membranes
      containing a synthetic substrate, and the membranes are examined for fluorescent
      foci under UV illumination. Fluorescent foci were produced by all the
      Vibrionaceae tested, including Vibrio spp., Aeromonas spp., and Plesiomonas spp.
      Fluorescence was not produced by non-Vibrionaceae pathogens. Vibrio cholerae
      strains O1, O139, O22, and O155 were strongly positive. Seawater and oysters were
      assayed, and 87 of 93 (93.5%) of the positive isolates were identified
      biochemically as Vibrionaceae, principally Vibrio vulnificus, Vibrio
      parahaemolyticus, Aeromonas hydrophila, Photobacterium damselae, and Shewanella
      putrefaciens. None of 50 nonfluorescent isolates were Vibrionaceae. No
      Vibrionaceae were detected in soil, and only A. hydrophila was detected in
      sewage. The COPP technique may be particularly valuable in environmental and food
      testing laboratories and for monitoring water quality in the aquaculture
      industry.

PMID- 16000758
TI  - Previously unknown virus infects marine diatom.
AB  - Diatoms are a major phytoplankton group that play important roles in maintaining
      oxygen levels in the atmosphere and sustaining the primary nutritional production
      of the aquatic environment. Among diatoms, the genus Chaetoceros is one of the
      most abundant and widespread. Temperature, climate, salinity, nutrients, and
      predators were regarded as important factors controlling the abundance and
      population dynamics of diatoms. Here we show that a viral infection can occur in
      the genus Chaetoceros and should therefore be considered as a potential mortality
      source. Chaetoceros salsugineum nuclear inclusion virus (CsNIV) is a 38-nm
      icosahedral virus that replicates within the nucleus of C. salsugineum. The
      latent period was estimated to be between 12 and 24 h, with a burst size of 325
      infectious units per host cell. CsNIV has a genome structure unlike that of other
      viruses that have been described. It consists of a single molecule of covalently
      closed circular single-stranded DNA (ssDNA; 6,005 nucleotides), as well as a
      segment of linear ssDNA (997 nucleotides). The linear segment is complementary to
      a portion of the closed circle creating a partially double-stranded genome.
      Sequence analysis reveals a low but significant similarity to the replicase of
      circoviruses that have a covalently closed circular ssDNA genome. This new host
      virus system will be useful for investigating the ecological relationships
      between bloom-forming diatoms and other viruses in the marine system. Our study
      supports the view that, given the diversity and abundance of plankton, the ocean
      is a treasury of undiscovered viruses.

PMID- 16000759
TI  - Survey of bovine enterovirus in biological and environmental samples by a highly
      sensitive real-time reverse transcription-PCR.
AB  - Animal enteroviruses shed in the feces of infected animals are likely
      environmental contaminants and thus can be used as indicators of animal fecal
      pollution. Previous work has demonstrated that bovine enterovirus (BEV) present
      in bovine feces contaminates waters adjacent to cattle herds and that BEV-like
      sequences are also present in shellfish and in deer feces from the same
      geographical area. However, little information is available about the prevalence,
      molecular epidemiology, and genomic sequence variation of BEV field isolates.
      Here we describe an optimized highly sensitive real-time reverse transcription
      PCR method to detect BEV RNA in biological and environmental samples. A
      combination of the amplification procedure with a previously described filtration
      step with electropositive filters allowed us to detect up to 12 BEV RNA molecules
      per ml of water. The feasibility of using the method to detect BEV in surface
      waters at a high risk of fecal pollution was confirmed after analysis of water
      samples obtained from different sources. The method was also used to study the
      prevalence of BEV in different cattle herds around Spain, and the results
      revealed that 78% (78 of 100) of the fecal samples were BEV positive. BEV-like
      sequences were also detected in feces from sheep, goats, and horses. Nucleotide
      sequence analyses showed that BEV isolates are quite heterogeneous and suggested
      the presence of species-specific BEV-like variants. Detection of BEV-like
      sequences may help in the differentiation and characterization of animal sources
      of contamination.

PMID- 16000760
TI  - Long-term population dynamics of phototrophic sulfur bacteria in the chemocline
      of Lake Cadagno, Switzerland.
AB  - Population analyses in water samples obtained from the chemocline of crenogenic,
      meromictic Lake Cadagno, Switzerland, in October for the years 1994 to 2003 were
      studied using in situ hybridization with specific probes. During this 10-year
      period, large shifts in abundance between purple and green sulfur bacteria and
      among different populations were obtained. Purple sulfur bacteria were the
      numerically most prominent phototrophic sulfur bacteria in samples obtained from
      1994 to 2001, when they represented between 70 and 95% of the phototrophic sulfur
      bacteria. All populations of purple sulfur bacteria showed large fluctuations in
      time with populations belonging to the genus Lamprocystis being numerically much
      more important than those of the genera Chromatium and Thiocystis. Green sulfur
      bacteria were initially represented by Chlorobium phaeobacteroides but were
      replaced by Chlorobium clathratiforme by the end of the study. C. clathratiforme
      was the only green sulfur bacterium detected during the last 2 years of the
      analysis, when a shift in dominance from purple sulfur bacteria to green sulfur
      bacteria was observed in the chemocline. At this time, numbers of purple sulfur
      bacteria had decreased and those of green sulfur bacteria increased by about 1
      order of magnitude and C. clathratiforme represented about 95% of the
      phototrophic sulfur bacteria. This major change in community structure in the
      chemocline was accompanied by changes in profiles of turbidity and
      photosynthetically available radiation, as well as for sulfide concentrations and
      light intensity. Overall, these findings suggest that a disruption of the
      chemocline in 2000 may have altered environmental niches and populations in
      subsequent years.

PMID- 16000761
TI  - Amino acid catabolism by an areA-regulated gene encoding an L-amino acid oxidase
      with broad substrate specificity in Aspergillus nidulans.
AB  - The filamentous fungus Aspergillus nidulans can use a wide range of compounds as
      nitrogen sources. The synthesis of the various catabolic enzymes needed to
      breakdown these nitrogen sources is regulated by the areA gene, which encodes a
      GATA transcription factor required to activate gene expression under nitrogen
      limiting conditions. The areA102 mutation results in pleiotropic effects on
      nitrogen source utilization, including better growth on certain amino acids as
      nitrogen sources. Mutations in the sarA gene were previously isolated as
      suppressors of the strong growth of an areA102 strain on l-histidine as a sole
      nitrogen source. We cloned the sarA gene by complementation of a sarA mutant and
      showed that it encodes an l-amino acid oxidase enzyme with broad substrate
      specificity. Elevated expression of this enzyme activity in an areA102 background
      accounts for the strong growth of these strains on amino acids that are
      substrates for this enzyme. Loss of function sarA mutations, which abolish the l
      amino acid oxidase activity, reverse the areA102 phenotype. Growth tests with
      areA102 and sarA mutants show that this enzyme is the primary route of catabolism
      for some amino acids, while other amino acids are metabolized through alternative
      pathways that yield either ammonium or glutamate for growth.

PMID- 16000762
TI  - Assessment of heat resistance of bacterial spores from food product isolates by
      fluorescence monitoring of dipicolinic acid release.
AB  - This study is aimed at the development and application of a convenient and rapid
      optical assay to monitor the wet-heat resistance of bacterial endospores
      occurring in food samples. We tested the feasibility of measuring the release of
      the abundant spore component dipicolinic acid (DPA) as a probe for heat
      inactivation. Spores were isolated from the laboratory type strain Bacillus
      subtilis 168 and from two food product isolates, Bacillus subtilis A163 and
      Bacillus sporothermodurans IC4. Spores from the lab strain appeared much less
      heat resistant than those from the two food product isolates. The decimal
      reduction times (D values) for spores from strains 168, A163, and IC4 recovered
      on Trypticase soy agar were 1.4, 0.7, and 0.3 min at 105 degrees C, 120 degrees
      C, and 131 degrees C, respectively. The estimated Z values were 6.3 degrees C,
      6.1 degrees C, and 9.7 degrees C, respectively. The extent of DPA release from
      the three spore crops was monitored as a function of incubation time and
      temperature. DPA concentrations were determined by measuring the emission at 545
      nm of the fluorescent terbium-DPA complex in a microtiter plate fluorometer. We
      defined spore heat resistance as the critical DPA release temperature (Tc), the
      temperature at which half the DPA content has been released within a fixed
      incubation time. We found Tc values for spores from Bacillus strains 168, A163,
      and IC4 of 108 degrees C, 121 degrees C, and 131 degrees C, respectively. On the
      basis of these observations, we developed a quantitative model that describes the
      time and temperature dependence of the experimentally determined extent of DPA
      release and spore inactivation. The model predicts a DPA release rate profile for
      each inactivated spore. In addition, it uncovers remarkable differences in the
      values for the temperature dependence parameters for the rate of spore
      inactivation, DPA release duration, and DPA release delay.

PMID- 16000763
TI  - Characterization of a new bacteriocin operon in sakacin P-producing Lactobacillus
      sakei, showing strong translational coupling between the bacteriocin and immunity
      genes.
AB  - Previous studies of genes involved in the production of sakacin P by
      Lactobacillus sakei Lb674 revealed the presence of an inducible promoter
      downstream of the known spp gene clusters. We show here that this promoter drives
      the expression of an operon consisting of a bacteriocin gene (sppQ), a cognate
      immunity gene (spiQ), another gene with an unknown function (orf4), and a
      pseudoimmunity gene containing a frameshift mutation (orf5). The leader peptide
      of the new one-peptide bacteriocin sakacin Q contains consensus elements that are
      typical for so-called "double-glycine" leader peptides. The mature bacteriocin
      shows weak similarity to the BrcA peptide of the two-peptide bacteriocin
      brochocin C. Sakacin Q has an antimicrobial spectrum that differs from that of
      sakacin P, thus expanding the antimicrobial properties of the producer strain.
      The genes encoding sakacin Q and its cognate immunity protein showed strong
      translational coupling, which was investigated in detail by analyzing the
      properties of a series of beta-glucuronidase fusions. Our results provide
      experimental evidence that production of the bacteriocin and production of the
      cognate immunity protein are tightly coregulated at the translational level.

PMID- 16000764
TI  - Seasonal variation in abundance of total and pathogenic Vibrio parahaemolyticus
      bacteria in oysters along the southwest coast of India.
AB  - The seasonal abundance of Vibrio parahaemolyticus in oysters from two estuaries
      along the southwest coast of India was studied by colony hybridization using
      nonradioactive labeled oligonucleotide probes. The density of total V.
      parahaemolyticus bacteria was determined using a probe binding to the tlh
      (thermolabile hemolysin) gene, and the density of pathogenic V. parahaemolyticus
      bacteria was determined by using a probe binding to the tdh (thermostable direct
      hemolysin) gene. Furthermore, the prevalence of V. parahaemolyticus was studied
      by PCR amplification of the toxR, tdh, and trh genes. PCR was performed directly
      with oyster homogenates and also following enrichment in alkaline peptone water
      for 6 and 18 h. V. parahaemolyticus was detected in 93.87% of the samples, and
      the densities ranged from <10 to 10(4) organisms per g. Pathogenic V.
      parahaemolyticus could be detected in 5 of 49 samples (10.2%) by colony
      hybridization using the tdh probe and in 3 of 49 samples (6.1%) by PCR. Isolates
      from one of the samples belonged to the pandemic serotype O3:K6. Twenty-nine of
      the 49 samples analyzed (59.3%) were positive as determined by PCR for the
      presence of the trh gene in the enrichment broth media. trh-positive V.
      parahaemolyticus was frequently found in oysters from India.

PMID- 16000765
TI  - Relative importance of bacteriocin-like genes in antagonism of Xanthomonas
      perforans tomato race 3 to Xanthomonas euvesicatoria tomato race 1 strains.
AB  - In a previous study, tomato race 3 (T3) strains of Xanthomonas perforans became
      predominant in fields containing both X. euvesicatoria and X. perforans races T1
      and T3, respectively. This apparent ability to take over fields led to the
      discovery that there are three bacteriocin-like compounds associated with T3
      strains. T3 strain 91-118 produces at least three different bacteriocin-like
      compounds (BCN-A, BCN-B, and BCN-C) antagonistic toward T1 strains. We determined
      the relative importance of the bacteriocin-like compounds by constructing the
      following mutant forms of a wild-type (WT) T3 strain to evaluate the antagonism
      to WT T1 strains: Mut-A (BCN-A-), Mut-B (BCN-B-), Mut-C (BCN-C-), Mut-AB, Mut-BC,
      and Mut-ABC. Although all mutant and WT T3 strains reduced the T1 populations in
      in planta growth room experiments, Mut-B and WT T3 were significantly more
      effective. Mutants expressing BCN-B and either BCN-A or BCN-C reduced T1
      populations less than mutants expressing only BCN-A or BCN-C. The triple-knockout
      mutant Mut-ABC also had a significant competitive advantage over the T1 strain.
      In pairwise-inoculation field experiments where plants were coinoculated with an
      individual mutant or WT T3 strain and the T1 strain, the mutant strains and the
      WT T3 strain were reisolated from more than 70% of the lesions. WT T3 and Mut-B
      were the most frequently reisolated strains. In field experiments where plants
      were group inoculated with Mut-A, Mut-B, Mut-C, Mut-ABC, and WT T1 and T3
      strains, Mut-B populations dominated all three seasons. In greenhouse and field
      experiments, the WT and mutant T3 strains had a selective advantage over T1
      strains. Bacterial strains expressing both BCN-A and BCN-C appeared to have a
      competitive advantage over all other mutant and WT strains. Furthermore, BCN-B
      appeared to be a negative factor, with mutant T3 strains lacking BCN-B having a
      selective advantage in the field.

PMID- 16000766
TI  - Identification and characterization of a second lexA gene of Xanthomonas
      axonopodis Pathovar citri.
AB  - We previously identified and characterized a lexA gene from Xanthomonas
      axonopodis pv. citri. For this study, we cloned and expressed a lexA homologue
      from X. axonopodis pv. citri. This gene was designated lexA2, and the previously
      identified lexA gene was renamed lexA1. The coding region of lexA2 is 606 bp long
      and shares 59% nucleotide sequence identity with lexA1. Analyses of the deduced
      amino acid sequence revealed that LexA2 has structures that are characteristic of
      LexA proteins, including a helix-turn-helix DNA binding domain and conserved
      amino acid residues required for the autocleavage of LexA. The lexA2 mutant,
      which was constructed by gene replacement, was 4 orders of magnitude more
      resistant to the DNA-damaging agent mitomycin C at 0.1 microg/ml and 1 order of
      magnitude more resistant to another DNA-damaging agent, methylmethane sulfonate
      at 30 microg/ml, than the wild type. A lexA1 lexA2 double mutant had the same
      degree of susceptibility to mitomycin C as the lexA1 or lexA2 single mutant but
      was 1 order of magnitude more resistant to methylmethane sulfonate at 30
      microg/ml than the lexA1 or lexA2 single mutant. These results suggest that LexA1
      and LexA2 play different roles in regulating the production of methyltransferases
      that are required for repairing DNA damage caused by methylmethane sulfonate. A
      mitomycin C treatment also caused LexA2 to undergo autocleavage, as seen with
      LexA1. The results of electrophoresis mobility shift assays revealed that LexA2
      does not bind the lexA1 promoter. It binds to both the lexA2 and recA promoters.
      However, neither LexA2 nor LexA1 appears to regulate recA expression, as lexA1,
      lexA2, and lexA1 lexA2 mutants did not become constitutive for recA transcription
      and RecA production. These results suggest that recA expression in X. axonopodis
      pv. citri is regulated by mechanisms that have yet to be identified.

PMID- 16000767
TI  - Algal viruses with distinct intraspecies host specificities include identical
      intein elements.
AB  - Heterosigma akashiwo virus (HaV) is a large double-stranded DNA virus infecting
      the single-cell bloom-forming raphidophyte (golden brown alga) H. akashiwo. A
      molecular phylogenetic sequence analysis of HaV DNA polymerase showed that it
      forms a sister group with Phycodnaviridae algal viruses. All 10 examined HaV
      strains, which had distinct intraspecies host specificities, included an intein
      (protein intron) in their DNA polymerase genes. The 232-amino-acid inteins
      differed from each other by no more than a single nucleotide change. All inteins
      were present at the same conserved position, coding for an active-site motif,
      which also includes inteins in mimivirus (a very large double-stranded DNA virus
      of amoebae) and in several archaeal DNA polymerase genes. The HaV intein is
      closely related to the mimivirus intein, and both are apparently monophyletic to
      the archaeal inteins. These observations suggest the occurrence of horizontal
      transfers of inteins between viruses of different families and between archaea
      and viruses and reveal that viruses might be reservoirs and intermediates in
      horizontal transmissions of inteins. The homing endonuclease domain of the HaV
      intein alleles is mostly deleted. The mechanism keeping their sequences basically
      identical in HaV strains specific for different hosts is yet unknown. One
      possibility is that rapid and local changes in the HaV genome change its host
      specificity. This is the first report of inteins found in viruses infecting
      eukaryotic algae.

PMID- 16000768
TI  - Cloning and sequencing of two Ceriporiopsis subvermispora bicupin oxalate oxidase
      allelic isoforms: implications for the reaction specificity of oxalate oxidases
      and decarboxylases.
AB  - Oxalate oxidase is thought to be involved in the production of hydrogen peroxide
      for lignin degradation by the dikaryotic white rot fungus Ceriporiopsis
      subvermispora. This enzyme was purified, and after digestion with trypsin,
      peptide fragments of the enzyme were sequenced using quadrupole time-of-flight
      mass spectrometry. Starting with degenerate primers based on the peptide
      sequences, two genes encoding isoforms of the enzyme were cloned, sequenced, and
      shown to be allelic. Both genes contained 14 introns. The sequences of the
      isoforms revealed that they were both bicupins that unexpectedly shared the
      greatest similarity to microbial bicupin oxalate decarboxylases rather than
      monocupin plant oxalate oxidases (also known as germins). We have shown that both
      fungal isoforms, one of which was heterologously expressed in Escherichia coli,
      are indeed oxalate oxidases that possess < or =0.2% oxalate decarboxylase
      activity and that the organism is capable of rapidly degrading exogenously
      supplied oxalate. They are therefore the first bicupin oxalate oxidases to have
      been described. Heterologous expression of active enzyme was dependent on the
      addition of manganese salts to the growth medium. Molecular modeling provides new
      and independent evidence for the identity of the catalytic site and the key amino
      acid involved in defining the reaction specificities of oxalate oxidases and
      oxalate decarboxylases.

PMID- 16000769
TI  - Metabolic engineering of anthocyanin biosynthesis in Escherichia coli.
AB  - Anthocyanins are red, purple, or blue plant pigments that belong to the family of
      polyphenolic compounds collectively called flavonoids. Their demonstrated
      antioxidant properties and economic importance to the dye, fruit, and cut-flower
      industries have driven intensive research into their metabolic biosynthetic
      pathways. In order to produce stable, glycosylated anthocyanins from colorless
      flavanones such as naringenin and eriodictyol, a four-step metabolic pathway was
      constructed that contained plant genes from heterologous origins: flavanone 3beta
      hydroxylase from Malus domestica, dihydroflavonol 4-reductase from Anthurium
      andraeanum, anthocyanidin synthase (ANS) also from M. domestica, and UDP
      glucose:flavonoid 3-O-glucosyltransferase from Petunia hybrida. Using two rounds
      of PCR, each one of the four genes was first placed under the control of the trc
      promoter and its own bacterial ribosome-binding site and then cloned sequentially
      into vector pK184. Escherichia coli cells containing the recombinant plant
      pathway were able to take up either naringenin or eriodictyol and convert it to
      the corresponding glycosylated anthocyanin, pelargonidin 3-O-glucoside or
      cyanidin 3-O-glucoside. The produced anthocyanins were present at low
      concentrations, while most of the metabolites detected corresponded to their
      dihydroflavonol precursors, as well as the corresponding flavonols. The presence
      of side product flavonols is at least partly due to an alternate reaction
      catalyzed by ANS. This is the first time plant-specific anthocyanins have been
      produced from a microorganism and opens up the possibility of further production
      improvement by protein and pathway engineering.

PMID- 16000770
TI  - Diversity of bacteria growing in natural mineral water after bottling.
AB  - Bacterial growth occurs in noncarbonated natural mineral waters a few days after
      filling and storage at room temperature, a phenomenon known for more than 40
      years. Using the full-cycle rRNA approach, we monitored the development of the
      planktonic bacterial community in a noncarbonated natural mineral water after
      bottling. Seven 16S rRNA gene libraries, comprising 108 clones in total, were
      constructed from water samples taken at various days after bottling and from two
      different bottle sizes. Sequence analyses identified 11 operational taxonomic
      units (OTUs), all but one affiliated with the betaproteobacterial order
      Burkholderiales (6 OTUs) or the class Alphaproteobacteria (4 OTUs). Fluorescence
      in situ hybridization (FISH) was applied in combination with DAPI (4',6'
      diamidino-2-phenylindole) staining, viability staining, and microscopic counting
      to quantitatively monitor changes in bacterial community composition. A growth
      curve similar to that of a bacterium grown in a batch culture was recorded. In
      contrast to the current perception that Gammaproteobacteria are the most
      important bacterial components of natural mineral water in bottles,
      Betaproteobacteria dominated the growing bacterial community and accounted for 80
      to 98% of all bacteria detected by FISH in the late-exponential and stationary
      growth phases. Using previously published and newly designed genus-specific
      probes, members of the betaproteobacterial genera Hydrogenophaga, Aquabacterium,
      and Polaromonas were found to constitute a significant proportion of the
      bacterial flora (21 to 86% of all bacteria detected by FISH). For the first time,
      key genera responsible for bacterial growth in a natural mineral water were
      identified by applying molecular cultivation-independent techniques.

PMID- 16000771
TI  - Purification and characterization of a novel alcohol dehydrogenase from Leifsonia
      sp. strain S749: a promising biocatalyst for an asymmetric hydrogen transfer
      bioreduction.
AB  - To find microorganisms that could reduce phenyl trifluoromethyl ketone (PTK) to
      (S)-1-phenyltrifluoroethanol [(S)-PTE], styrene-assimilating bacteria (ca. 900
      strains) isolated from soil samples were screened. We found that Leifsonia sp.
      strain S749 was the most suitable strain for the conversion of PTK to (S)-PTE in
      the presence of 2-propanol as a hydrogen donor. The enzyme corresponding to the
      reaction was purified homogeneity, characterized and designated Leifsonia alcohol
      dehydrogenase (LSADH). The purified enzyme had a molecular weight of 110,000 and
      was composed of four identical subunits (molecular weight, 26,000). LSADH
      required NADH as a cofactor, showed little activity with NADPH, and reduced a
      wide variety of aldehydes and ketones. LSADH catalyzed the enantioselective
      reduction of some ketones with high enantiomeric excesses (e.e.): PTK to (S)-PTE
      (>99% e.e.), acetophenone to (R)-1-phenylethanol (99% e.e.), and 2-heptanone to
      (R)-2-heptanol (>99% e.e.) in the presence of 2-propanol without an additional
      NADH regeneration system. Therefore, it would be a useful biocatalyst.

PMID- 16000772
TI  - Degradation of cyanophycin by Sedimentibacter hongkongensis strain KI and
      Citrobacter amalonaticus strain G Isolated from an anaerobic bacterial
      consortium.
AB  - Using a combination of various enrichment techniques, the strictly anaerobic,
      gram-positive, endospore-forming bacterium Sedimentibacter hongkongensis strain
      KI as revealed by 16S rRNA analysis and the gram-negative enterobacterium
      Citrobacter amalonaticus strain G as revealed by physiological tests were
      isolated from an anaerobic cyanophycin (CGP)-degrading bacterial consortium. S.
      hongkongensis strain KI is the first anaerobic bacterium with the ability to
      hydrolyze CGP to beta-Asp-Arg and beta-Asp-Lys dipeptides, as revealed by
      electrospray ionization-mass spectrometry and reversed-phase high-performance
      liquid chromatography analysis. However, these primary accumulated hydrolysis
      products were only partially used by S. hongkongensis strain KI, and significant
      growth on CGP did not occur. On the other hand, C. amalonaticus strain G did not
      degrade CGP but grew on the beta-linked iso-dipeptides formed in vitro by
      enzymatic CGP degradation or in vivo by metabolic activity of S. hongkongensis
      strain KI. Dipeptide utilization occurred at the highest rate if both strains
      were used in cocultivation experiments with CGP, indicating that cooperation
      between different bacteria occurs in anaerobic natural environments for complete
      CGP turnover. The amino acids obtained from the cleavage of dipeptides were
      fermented to ethanol, acetic acid, and succinic acid, as revealed by gas
      chromatographic analysis and by spectrophotometric enzyme assays.

PMID- 16000773
TI  - Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as
      cholesterol synthesis inhibitors.
AB  - Ganoderma lucidum is a medicinal fungus belonging to the Polyporaceae family
      which has long been known in Japan as Reishi and has been used extensively in
      traditional Chinese medicine. We report the isolation and identification of the
      26-oxygenosterols ganoderol A, ganoderol B, ganoderal A, and ganoderic acid Y and
      their biological effects on cholesterol synthesis in a human hepatic cell line in
      vitro. We also investigated the site of inhibition in the cholesterol synthesis
      pathway. We found that these oxygenated sterols from G. lucidum inhibited
      cholesterol biosynthesis via conversion of acetate or mevalonate as a precursor
      of cholesterol. By incorporation of 24,25-dihydro-[24,25-3H2]lanosterol and [3
      3H]lathosterol in the presence of ganoderol A, we determined that the point of
      inhibition of cholesterol synthesis is between lanosterol and lathosterol. These
      results demonstrate that the lanosterol 14alpha-demethylase, which converts 24,25
      dihydrolanosterol to cholesterol, can be inhibited by the 26-oxygenosterols from
      G. lucidum. These 26-oxygenosterols could lead to novel therapeutic agents that
      lower blood cholesterol.

PMID- 16000774
TI  - Molecular and biochemical analysis of the galactose phenotype of dairy
      Streptococcus thermophilus strains reveals four different fermentation profiles.
AB  - Lactose-limited fermentations of 49 dairy Streptococcus thermophilus strains
      revealed four distinct fermentation profiles with respect to galactose
      consumption after lactose depletion. All the strains excreted galactose into the
      medium during growth on lactose, except for strain IMDOST40, which also displayed
      extremely high galactokinase (GalK) activity. Among this strain collection eight
      galactose-positive phenotypes sensu stricto were found and their fermentation
      characteristics and Leloir enzyme activities were measured. As the gal promoter
      seems to play an important role in the galactose phenotype, the galR-galK
      intergenic region was sequenced for all strains yielding eight different
      nucleotide sequences (NS1 to NS8). The gal promoter played an important role in
      the Gal-positive phenotype but did not determine it exclusively. Although GalT
      and GalE activities were detected for all Gal-positive strains, GalK activity
      could only be detected for two out of eight Gal-positive strains. This finding
      suggests that the other six S. thermophilus strains metabolize galactose via an
      alternative route. For each type of fermentation profile obtained, a
      representative strain was chosen and four complete Leloir gene clusters were
      sequenced. It turned out that Gal-positive strains contained more amino acid
      differences within their gal genes than Gal-negative strains. Finally, the
      biodiversity regarding lactose-galactose utilization among the different S.
      thermophilus strains used in this study was shown by RAPD-PCR. Five Gal-positive
      strains that contain nucleotide sequence NS2 in their galR-galK intergenic region
      were closely related.

PMID- 16000775
TI  - Influence of fluid shear and microbubbles on bacterial detachment from a surface.
AB  - Prevention of microbial adhesion and detachment of adhering microorganisms from
      surfaces is important in many environmental, industrial, and medical
      applications. Fluid shear is an obvious parameter for stimulating microbial
      detachment from surfaces, but recently it has been pointed out that a passing air
      liquid interface also has potential in stimulating microbial detachment. In the
      present study, the ability of microbubbles to stimulate detachment of bacterial
      strains from a glass surface is compared with the effects of fluid flow. Adhesion
      and detachment of Actinomyces naeslundii T14V-J1, Streptococcus oralis J22, and
      their coadhering aggregates were studied on glass, mounted in a parallel plate
      flow chamber. High fluid wall shear rates (11,000 to 16,000 s(-1)) were
      established in a laminar flow regime in the absence and presence of microbubbles.
      Wall shear rates stimulated detachment ranging from 70% to 30% for S. oralis and
      A. naeslundii, respectively. Coadhering aggregates were detached up to 54%. The
      presence of microbubbles in the flow increased the detachment of A. naeslundii
      within 2 min of flow from 40% in the absence of microbubbles to 98%, while
      detachment of neither S. oralis nor coadhering aggregates was affected by the
      presence of microbubbles. In summary, extremely high fluid flows can be effective
      in stimulating microbial detachment, depending on the strain involved. The
      addition of microbubbles to the flow allows the detachment of tenaciously
      adhering bacteria not detached by flow alone, but not of adhering coaggregates.

PMID- 16000776
TI  - Identification and characterization of pathogenic Yersinia enterocolitica
      isolates by PCR and pulsed-field gel electrophoresis.
AB  - Approximately 550 to 600 yersiniosis patients are reported annually in Sweden.
      Although pigs are thought to be the main reservoir of food-borne pathogenic
      Yersinia enterocolitica, the role of pork meat as a vehicle for transmission to
      humans is still unclear. Pork meat collected from refrigerators and local shops
      frequented by yersiniosis patients (n=48) were examined for the presence of
      pathogenic Yersinia spp. A combined culture and PCR method was used for
      detection, and a multiplex PCR was developed and evaluated as a tool for
      efficient identification of pathogenic food and patient isolates. The results
      obtained with the multiplex PCR were compared to phenotypic test results and
      confirmed by pulsed-field gel electrophoresis (PFGE). In all, 118 pork products
      (91 raw and 27 ready-to-eat) were collected. Pathogenic Yersinia spp. were
      detected by PCR in 10% (9 of 91) of the raw pork samples (loin of pork, fillet of
      pork, pork chop, ham, and minced meat) but in none of the ready-to-eat products.
      Isolates of Y. enterocolitica bioserotype 4/O:3 were recovered from six of the
      PCR-positive raw pork samples; all harbored the virulence plasmid. All isolates
      were recovered from food collected in shops and, thus, none were from the
      patients' home. When subjected to PFGE, the six isolates displayed four different
      NotI profiles. The same four NotI profiles were also present among isolates
      recovered from the yersiniosis patients. The application of a multiplex PCR was
      shown to be an efficient tool for identification of pathogenic Y. enterocolitica
      isolates in naturally contaminated raw pork.

PMID- 16000777
TI  - Survey of motile microaerophilic bacterial morphotypes in the oxygen gradient
      above a marine sulfidic sediment.
AB  - Enrichment cultures for free-swimming microaerophilic bacteria were prepared from
      marine sulfidic sediment samples (Niva Bay, Denmark). We observed nine different
      morphotypes; three of these morphotypes represented already-described species,
      i.e., Thiovulum majus, "Candidatus Ovobacter propellens," and an as-yet-unnamed
      large vibrioid bacterium. In addition, we observed several morphotypes of
      spirilla and one vibrioid morphotype. A common feature of all investigated
      bacteria was that they aggregated chemotactically at the oxic-anoxic interface,
      whereas preferred oxygen concentration were in the range of 1 to 10 muM. The
      motile behavior and flagellar dynamics are analyzed in detail with an emphasis on
      spirilla.

PMID- 16000778
TI  - pH and peptide supply can radically alter bacterial populations and short-chain
      fatty acid ratios within microbial communities from the human colon.
AB  - The effects of changes in the gut environment upon the human colonic microbiota
      are poorly understood. The response of human fecal microbial communities from two
      donors to alterations in pH (5.5 or 6.5) and peptides (0.6 or 0.1%) was studied
      here in anaerobic continuous cultures supplied with a mixed carbohydrate source.
      Final butyrate concentrations were markedly higher at pH 5.5 (0.6% peptide mean,
      24.9 mM; 0.1% peptide mean, 13.8 mM) than at pH 6.5 (0.6% peptide mean, 5.3 mM;
      0.1% peptide mean, 7.6 mM). At pH 5.5 and 0.6% peptide input, a high butyrate
      production coincided with decreasing acetate concentrations. The highest
      propionate concentrations (mean, 20.6 mM) occurred at pH 6.5 and 0.6% peptide
      input. In parallel, major bacterial groups were monitored by using fluorescence
      in situ hybridization with a panel of specific 16S rRNA probes. Bacteroides
      levels increased from ca. 20 to 75% of total eubacteria after a shift from pH 5.5
      to 6.5, at 0.6% peptide, coinciding with high propionate formation. Conversely,
      populations of the butyrate-producing Roseburia group were highest (11 to 19%) at
      pH 5.5 but fell at pH 6.5, a finding that correlates with butyrate formation.
      When tested in batch culture, three Bacteroides species grew well at pH 6.7 but
      poorly at pH 5.5, which is consistent with the behavior observed for the mixed
      community. Two Roseburia isolates grew equally well at pH 6.7 and 5.5. These
      findings suggest that a lowering of pH resulting from substrate fermentation in
      the colon may boost butyrate production and populations of butyrate-producing
      bacteria, while at the same time curtailing the growth of Bacteroides spp.

PMID- 16000779
TI  - Potential regrowth and recolonization of salmonellae and indicators in biosolids
      and biosolid-amended soil.
AB  - This study evaluated the potential for conversion of Class B to Class A biosolids
      with respect to salmonellae and fecal coliforms during solar drying in concrete
      lined drying beds. Anaerobically (8% solids) and aerobically (2% solids) digested
      Class B biosolids were pumped into field-scale drying beds, and microbial
      populations and environmental conditions were monitored. Numbers of fecal
      coliforms and salmonellae decreased as temperature and rate of desiccation
      increased. After 3 to 4 weeks, Class A requirements were achieved in both
      biosolids for the pathogens and the indicators. However, following rainfall
      events, significant increase in numbers was observed for both fecal coliforms and
      salmonellae. In laboratory studies, regrowth of fecal coliforms was observed in
      both biosolids and biosolid-amended soil, but the regrowth of salmonellae
      observed in the concrete-lined drying beds did not occur. These laboratory
      studies demonstrated that pathogens decreased in numbers when soil was amended
      with biosolids. Based on serotyping, the increased numbers of salmonellae seen in
      the concrete lined drying beds following rainfall events was most likely due to
      recolonization due to contamination from fecal matter introduced by animals and
      not from regrowth of salmonellae indigenous to biosolids. Overall, we conclude
      that the use of concrete-lined beds created a situation in which moisture added
      as rainfall accumulated in the beds, promoting the growth of fecal coliforms and
      salmonellae added from external sources.

PMID- 16000780
TI  - AmyA, an alpha-amylase with beta-cyclodextrin-forming activity, and AmyB from the
      thermoalkaliphilic organism Anaerobranca gottschalkii: two alpha-amylases adapted
      to their different cellular localizations.
AB  - Two alpha-amylase genes from the thermophilic alkaliphile Anaerobranca
      gottschalkii were cloned, and the corresponding enzymes, AmyA and AmyB, were
      investigated after purification of the recombinant proteins. Based on their amino
      acid sequences, AmyA is proposed to be a lipoprotein with extracellular
      localization and thus is exposed to the alkaline milieu, while AmyB apparently
      represents a cytoplasmic enzyme. The amino acid sequences of both enzymes bear
      high similarity to those of GHF13 proteins. The different cellular localizations
      of AmyA and AmyB are reflected in their physicochemical properties. The alkaline
      pH optimum (pH 8), as well as the broad pH range, of AmyA activity (more than 50%
      activity between pH 6 and pH 9.5) mirrors the conditions that are encountered by
      an extracellular enzyme exposed to the medium of A. gottschalkii, which grows
      between pH 6 and pH 10.5. AmyB, on the other hand, has a narrow pH range with a
      slightly acidic pH optimum at 6 to 6.5, which is presumably close to the pH in
      the cytoplasm. Also, the intracellular AmyB is less tolerant of high temperatures
      than the extracellular AmyA. While AmyA has a half-life of 48 h at 70 degrees C,
      AmyB has a half-life of only about 10 min at that temperature, perhaps due to the
      lack of stabilizing constituents of the cytoplasm. AmyA and AmyB were very
      similar with respect to their substrate specificity profiles, clearly preferring
      amylose over amylopectin, pullulan, and glycogen. Both enzymes also hydrolyzed
      alpha-, beta-, and gamma-cyclodextrin. Very interestingly, AmyA, but not AmyB,
      displayed high transglycosylation activity on maltooligosaccharides and also had
      significant beta-cyclodextrin glycosyltransferase (CGTase) activity. CGTase
      activity has not been reported for typical alpha-amylases before. The mechanism
      of cyclodextrin formation by AmyA is unknown.

PMID- 16000781
TI  - Identification of a positive transcription regulatory element within the coding
      region of the nifLA operon in Azotobacter vinelandii.
AB  - Nitrogen fixation in Azotobacter vinelandii is regulated by the nifLA operon.
      NifA activates the transcription of nif genes, while NifL antagonizes the
      transcriptional activator NifA in response to fixed nitrogen and molecular oxygen
      levels. However, transcriptional regulation of the nifLA operon of A. vinelandii
      itself is not fully understood. Using the S1 nuclease assay, we mapped the
      transcription start site of the nifLA operon, showing it to be similar to the
      sigma54-dependent promoters. We also identified a positive cis-acting regulatory
      element (+134 to +790) of the nifLA operon within the coding region of the nifL
      gene of A. vinelandii. Deletion of this element results in complete loss of
      promoter activity. Several protein factors bind to this region, and the specific
      binding sites have been mapped by DNase I foot printing. Two of these sites,
      namely dR1 (+134 to +204) and dR2 (+745 to +765), are involved in regulating the
      nifLA promoter activity. The absence of NtrC-like binding sites in the upstream
      region of the nifLA operon in A. vinelandii makes the identification of these
      downstream elements a highly significant finding. The interaction of the promoter
      with the proteins binding to the dR2 region spanning +745 to +765 appears to be
      dependent on the face of the helix as introduction of 4 bases just before this
      region completely disrupts promoter activity. Thus, the positive regulatory
      element present within the BglII-BglII fragment may play, in part; an important
      role in nifLA regulation in A. vinelandii.

PMID- 16000782
TI  - Growth and population dynamics of anaerobic methane-oxidizing archaea and sulfate
      reducing bacteria in a continuous-flow bioreactor.
AB  - The consumption of methane in anoxic marine sediments is a biogeochemical
      phenomenon mediated by two archaeal groups (ANME-1 and ANME-2) that exist
      syntrophically with sulfate-reducing bacteria. These anaerobic methanotrophs have
      yet to be recovered in pure culture, and key aspects of their ecology and
      physiology remain poorly understood. To characterize the growth and physiology of
      these anaerobic methanotrophs and the syntrophic sulfate-reducing bacteria, we
      incubated marine sediments using an anoxic, continuous-flow bioreactor during two
      experiments at different advective porewater flow rates. We examined the growth
      kinetics of anaerobic methanotrophs and Desulfosarcina-like sulfate-reducing
      bacteria using quantitative PCR as a proxy for cell counts, and measured methane
      oxidation rates using membrane-inlet mass spectrometry. Our data show that the
      specific growth rates of ANME-1 and ANME-2 archaea differed in response to
      porewater flow rates. ANME-2 methanotrophs had the highest rates in lower-flow
      regimes (mu(ANME-2) = 0.167 . week(-1)), whereas ANME-1 methanotrophs had the
      highest rates in higher-flow regimes (mu(ANME-1) = 0.218 . week(-1)). In both
      incubations, Desulfosarcina-like sulfate-reducing bacterial growth rates were
      approximately 0.3 . week(-1), and their growth dynamics suggested that sulfate
      reducing bacterial growth might be facilitated by, but not dependent upon, an
      established anaerobic methanotrophic population. ANME-1 growth rates corroborate
      field observations that ANME-1 archaea flourish in higher-flow regimes. Our
      growth and methane oxidation rates jointly demonstrate that anaerobic
      methanotrophs are capable of attaining substantial growth over a range of
      environmental conditions used in these experiments, including relatively low
      methane partial pressures.

PMID- 16000783
TI  - Isolation and detection of enterovirus RNA from large-volume water samples by
      using the NucliSens miniMAG system and real-time nucleic acid sequence-based
      amplification.
AB  - Concentration of water samples is a prerequisite for the detection of the low
      virus levels that are present in water and may present a public health hazard.
      The aim of this study was to develop a rapid, standardized molecular method for
      the detection of enteroviruses in large-volume surface water samples, using a
      concentration method suitable for the detection of infectious viruses as well as
      virus RNA. Concentration of water was achieved by a conventional filter
      adsorption-elution method and ultrafiltration, resulting in a 10,000-fold
      concentration of the sample. Isolation of virus RNA by a silica-based RNA
      extraction method was compared with the nonmagnetic and magnetic NucliSens RNA
      isolation methods. By using the silica-based RNA extraction method in two out of
      five samples, enterovirus RNA was detected, whereas four out of five samples were
      positive following RNA isolation with magnetic silica beads. Moreover, estimated
      RNA levels increased at least 100 to 500 times. Furthermore, we compared
      enterovirus detection by an in-house reverse transcription (RT)-PCR with a novel
      commercially available real-time nucleic acid sequence-based amplification
      (NASBA) assay. We found that the rapid real-time NASBA assay was slightly less
      sensitive than our in-house RT-PCR. The advantages, however, of a commercial real
      time NASBA assay, like the presence of an internal control RNA, standardization,
      and enormous decrease in turnaround time, makes it an attractive alternative to
      RT-PCR.

PMID- 16000784
TI  - Dehalogenation of the herbicides bromoxynil (3,5-dibromo-4-hydroxybenzonitrile)
      and ioxynil (3,5-diiodino-4-hydroxybenzonitrile) by Desulfitobacterium
      chlororespirans.
AB  - Desulfitobacterium chlororespirans has been shown to grow by coupling the
      oxidation of lactate to the metabolic reductive dehalogenation of ortho chlorines
      on polysubstituted phenols. Here, we examine the ability of D. chlororespirans to
      debrominate and deiodinate the polysubstituted herbicides bromoxynil (3,5-dibromo
      4-hydroxybenzonitrile), ioxynil (3,5-diiodo-4-hydroxybenzonitrile), and the
      bromoxynil metabolite 3,5-dibromo-4-hydroxybenzoate (DBHB). Stoichiometric
      debromination of bromoxynil to 4-cyanophenol and DBHB to 4-hydroxybenzoate
      occurred. Further, bromoxynil (35 to 75 microM) and DBHB (250 to 260 microM) were
      used as electron acceptors for growth. Doubling times for growth (means +/-
      standard deviations for triplicate cultures) on bromoxynil (18.4 +/- 5.2 h) and
      DBHB (11.9 +/- 1.4 h), determined by rate of [14C]lactate uptake into biomass,
      were similar to those previously reported for this microorganism during growth on
      pyruvate (15.4 h). In contrast, ioxynil was not deiodinated when added alone or
      when added with bromoxynil; however, ioxynil dehalogenation, with stoichiometric
      conversion to 4-cyanophenol, was observed when the culture was amended with 3
      chloro-4-hydroxybenzoate (a previously reported electron acceptor). To our
      knowledge, this is the first direct report of deiodination by a bacterium in the
      Desulfitobacterium genus and the first report of an anaerobic pure culture with
      the ability to transform bromoxynil or ioxynil. This research provides valuable
      insights into the substrate range of D. chlororespirans.

PMID- 16000785
TI  - Hyaluronic acid production in Bacillus subtilis.
AB  - The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan
      synthase, has been expressed in Bacillus subtilis, resulting in the production of
      hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and
      tested, all of which contain the hasA gene along with one or more genes encoding
      enzymes involved in the synthesis of the UDP-precursor sugars that are required
      for HA synthesis. It was determined that the production of UDP-glucuronic acid is
      limiting in B. subtilis and that overexpressing the hasA gene along with the
      endogenous tuaD gene is sufficient for high-level production of HA. In addition,
      the B. subtilis-derived material was shown to be secreted and of high quality,
      comparable to commercially available sources of HA.

PMID- 16000786
TI  - Empirical establishment of oligonucleotide probe design criteria.
AB  - Criteria for the design of gene-specific and group-specific oligonucleotide
      probes were established experimentally via an oligonucleotide array that
      contained perfect match (PM) and mismatch probes (50-mers and 70-mers) based upon
      four genes. The effects of probe-target identity, continuous stretch, mismatch
      position, and hybridization free energy on specificity were tested. Little
      hybridization was observed at a probe-target identity of < or =85% for both 50
      mer and 70-mer probes. PM signal intensities (33 to 48%) were detected at a probe
      target identity of 94% for 50-mer oligonucleotides and 43 to 55% for 70-mer
      probes at a probe-target identity of 96%. When the effects of sequence identity
      and continuous stretch were considered independently, a stretch probe (>15 bases)
      contributed an additional 9% of the PM signal intensity compared to a nonstretch
      probe (< or =15 bases) at the same identity level. Cross-hybridization increased
      as the length of continuous stretch increased. A 35-base stretch for 50-mer
      probes or a 50-base stretch for 70-mer probes had approximately 55% of the PM
      signal. Little cross-hybridization was observed for probes with a minimal binding
      free energy greater than -30 kcal/mol for 50-mer probes or -40 kcal/mol for 70
      mer probes. Based on the experimental results, a set of criteria are suggested
      for the design of gene-specific and group-specific oligonucleotide probes, and
      the experimentally established criteria should provide valuable information for
      new software and algorithms for microarray-based studies.

PMID- 16000787
TI  - Enhanced trehalose production improves growth of Escherichia coli under osmotic
      stress.
AB  - The biosynthesis of trehalose has been previously shown to serve as an important
      osmoprotectant and stress protectant in Escherichia coli. Our results indicate
      that overproduction of trehalose (integrated lacI-Ptac-otsBA) above the level
      produced by the native regulatory system can be used to increase the growth of E.
      coli in M9-2% glucose medium at 37 degrees C to 41 degrees C and to increase
      growth at 37 degrees C in the presence of a variety of osmotic-stress agents
      (hexose sugars, inorganic salts, and pyruvate). Smaller improvements were noted
      with xylose and some fermentation products (ethanol and pyruvate). Based on these
      results, overproduction of trehalose may be a useful trait to include in
      biocatalysts engineered for commodity chemicals.

PMID- 16000788
TI  - Effect of low sulfate concentrations on lactate oxidation and isotope
      fractionation during sulfate reduction by Archaeoglobus fulgidus strain Z.
AB  - The effect of low substrate concentrations on the metabolic pathway and sulfur
      isotope fractionation during sulfate reduction was investigated for Archaeoglobus
      fulgidus strain Z. This archaeon was grown in a chemostat with sulfate
      concentrations between 0.3 mM and 14 mM at 80 degrees C and with lactate as the
      limiting substrate. During sulfate reduction, lactate was oxidized to acetate,
      formate, and CO2. This is the first time that the production of formate has been
      reported for A. fulgidus. The stoichiometry of the catabolic reaction was
      strongly dependent on the sulfate concentration. At concentrations of more than
      300 microM, 1 mol of sulfate was reduced during the consumption of 1 mol of
      lactate, whereas only 0.6 mol of sulfate was consumed per mol of lactate oxidized
      at a sulfate concentration of 300 microM. Furthermore, at low sulfate
      concentrations acetate was the main carbon product, in contrast to the CO2
      produced at high concentrations. We suggest different pathways for lactate
      oxidation by A. fulgidus at high and low sulfate concentrations. At about 300
      microM sulfate both the growth yield and the isotope fractionation were limited
      by sulfate, whereas the sulfate reduction rate was not limited by sulfate. We
      suggest that the cell channels more energy for sulfate uptake at sulfate
      concentrations below 300 to 400 microM than it does at higher concentrations.
      This could explain the shift in the metabolic pathway and the reduced growth
      yield and isotope fractionation at low sulfate levels.

PMID- 16000789
TI  - Changes in race-specific virulence in Pseudomonas syringae pv. phaseolicola are
      associated with a chimeric transposable element and rare deletion events in a
      plasmid-borne pathogenicity island.
AB  - Virulence for bean and soybean is determined by effector genes in a plasmid-borne
      pathogenicity island (PAI) in race 7 strain 1449B of Pseudomonas syringae pv.
      phaseolicola. One of the effector genes, avrPphF, confers either pathogenicity,
      virulence, or avirulence depending on the plant host and is absent from races 2,
      3, 4, 6, and 8 of this pathogen. Analysis of cosmid clones and comparison of DNA
      sequences showed that the absence of avrPphF from strain 1448A is due to deletion
      of a continuous 9.5-kb fragment. The remainder of the PAI is well conserved in
      strains 1448A and 1449B. The left junction of the deleted region consists of a
      chimeric transposable element generated from the fusion of homologs of IS1492
      from Pseudomonas putida and IS1090 from Ralstonia eutropha. The borders of the
      deletion were conserved in 66 P. syringae pv. phaseolicola strains isolated in
      different countries and representing the five races lacking avrPphF. However, six
      strains isolated in Spain had a 10.5-kb deletion that extended 1 kb further from
      the right junction. The perfect conservation of the 28-nucleotide right repeat of
      the IS1090 homolog in the two deletion types and in the other 47 insertions of
      the IS1090 homolog in the 1448A genome strongly suggests that the avrPphF
      deletions were mediated by the activity of the chimeric mobile element. Our data
      strongly support a clonal origin for the races of P. syringae pv. phaseolicola
      lacking avrPphF.

PMID- 16000790
TI  - Suppression of damping-off disease in host plants by the rhizoplane bacterium
      Lysobacter sp. strain SB-K88 is linked to plant colonization and antibiosis
      against soilborne Peronosporomycetes.
AB  - We previously demonstrated that xanthobaccin A from the rhizoplane bacterium
      Lysobacter sp. strain SB-K88 suppresses damping-off disease caused by Pythium sp.
      in sugar beet. In this study we focused on modes of Lysobacter sp. strain SB-K88
      root colonization and antibiosis of the bacterium against Aphanomyces
      cochlioides, a pathogen of damping-off disease. Scanning electron microscopic
      analysis of 2-week-old sugar beet seedlings from seeds previously inoculated with
      SB-K88 revealed dense colonization on the root surfaces and a characteristic
      perpendicular pattern of Lysobacter colonization possibly generated via
      development of polar, brush-like fimbriae. In colonized regions a semitransparent
      film apparently enveloping the root and microcolonies were observed on the root
      surface. This Lysobacter strain also efficiently colonized the roots of several
      plants, including spinach, tomato, Arabidopsis thaliana, and Amaranthus
      gangeticus. Plants grown from both sugar beet and spinach seeds that were
      previously treated with Lysobacter sp. strain SB-K88 displayed significant
      resistance to the damping-off disease triggered by A. cochlioides. Interestingly,
      zoospores of A. cochlioides became immotile within 1 min after exposure to a SB
      K88 cell suspension, a cell-free supernatant of SB-K88, or pure xanthobaccin A
      (MIC, 0.01 microg/ml). In all cases, lysis followed within 30 min in the presence
      of the inhibiting factor(s). Our data indicate that Lysobacter sp. strain SB-K88
      has a direct inhibitory effect on A. cochlioides, suppressing damping-off
      disease. Furthermore, this inhibitory effect of Lysobacter sp. strain SB-K88 is
      likely due to a combination of antibiosis and characteristic biofilm formation at
      the rhizoplane of the host plant.

PMID- 16000791
TI  - Isolation of soil bacteria adapted to degrade humic acid-sorbed phenanthrene.
AB  - The goal of these studies was to determine how sorption by humic acids affected
      the bioavailability of polynuclear aromatic hydrocarbons (PAHs) to PAH-degrading
      microbes. Micellar solutions of humic acid were used as sorbents, and
      phenanthrene was used as a model PAH. Enrichments from PAH-contaminated soils
      established with nonsorbed phenanthrene yielded a total of 25 different isolates
      representing a diversity of bacterial phylotypes. In contrast, only three strains
      of Burkholderia spp. and one strain each of Delftia sp. and Sphingomonas sp. were
      isolated from enrichments with humic acid-sorbed phenanthrene (HASP). Using
      [14C]phenanthrene as a radiotracer, we verified that only HASP isolates were
      capable of mineralizing HASP, a phenotype hence termed "competence." Competence
      was an all-or-nothing phenotype: noncompetent strains showed no detectable
      phenanthrene mineralization in HASP cultures, but levels of phenanthrene
      mineralization effected by competent strains in HASP and NSP cultures were not
      significantly different. Levels and rates of phenanthrene mineralization exceeded
      those predicted to be supported solely by the metabolism of phenanthrene in the
      aqueous phase of HASP cultures. Thus, competent strains were able to directly
      access phenanthrene sorbed by the humic acids and did not rely on desorption for
      substrate uptake. To the best of our knowledge, this is the first report of (i) a
      selective interaction between aerobic bacteria and humic acid molecules and (ii)
      differential bioavailability to bacteria of PAHs sorbed to a natural
      biogeopolymer.

PMID- 16000792
TI  - Purification, characterization, and crystallization of the components of the
      nitrobenzene and 2-nitrotoluene dioxygenase enzyme systems.
AB  - The protein components of the 2-nitrotoluene (2NT) and nitrobenzene dioxygenase
      enzyme systems from Acidovorax sp. strain JS42 and Comamonas sp. strain JS765,
      respectively, were purified and characterized. These enzymes catalyze the initial
      step in the degradation of 2-nitrotoluene and nitrobenzene. The identical shared
      reductase and ferredoxin components were monomers of 35 and 11.5 kDa,
      respectively. The reductase component contained 1.86 g-atoms iron, 2.01 g-atoms
      sulfur, and one molecule of flavin adenine dinucleotide per monomer. Spectral
      properties of the reductase indicated the presence of a plant-type [2Fe-2S]
      center and a flavin. The reductase catalyzed the reduction of cytochrome c,
      ferricyanide, and 2,6-dichlorophenol indophenol. The ferredoxin contained 2.20 g
      atoms iron and 1.99 g-atoms sulfur per monomer and had spectral properties
      indicative of a Rieske [2Fe-2S] center. The ferredoxin component could be
      effectively replaced by the ferredoxin from the Pseudomonas sp. strain NCIB 9816
      4 naphthalene dioxygenase system but not by that from the Burkholderia sp. strain
      LB400 biphenyl or Pseudomonas putida F1 toluene dioxygenase system. The
      oxygenases from the 2-nitrotoluene and nitrobenzene dioxygenase systems each had
      spectral properties indicating the presence of a Rieske [2Fe-2S] center, and the
      subunit composition of each oxygenase was an alpha(3)beta(3) hexamer. The
      apparent K(m) of 2-nitrotoluene dioxygenase for 2NT was 20 muM, and that for
      naphthalene was 121 muM. The specificity constants were 7.0 muM(-1) min(-1) for
      2NT and 1.2 muM(-1) min(-1) for naphthalene, indicating that the enzyme is more
      efficient with 2NT as a substrate. Diffraction-quality crystals of the two
      oxygenases were obtained.

PMID- 16000793
TI  - Dynamics of an oligotrophic bacterial aquifer community during contact with a
      groundwater plume contaminated with benzene, toluene, ethylbenzene, and xylenes:
      an in situ mesocosm study.
AB  - An in situ mesocosm system was designed to monitor the in situ dynamics of the
      microbial community in polluted aquifers. The mesocosm system consists of a
      permeable membrane pocket filled with aquifer material and placed within a
      polypropylene holder, which is inserted below groundwater level in a monitoring
      well. After a specific time period, the microcosm is recovered from the well and
      its bacterial community is analyzed. Using this system, we examined the effect of
      benzene, toluene, ethylbenzene, and xylene (BTEX) contamination on the response
      of an aquifer bacterial community by denaturing gradient gel electrophoresis
      analysis of PCR-amplified 16S rRNA genes and PCR detection of BTEX degradation
      genes. Mesocosms were filled with nonsterile or sterile aquifer material derived
      from an uncontaminated area and positioned in a well located in either the
      uncontaminated area or a nearby contaminated area. In the contaminated area, the
      bacterial community in the microcosms rapidly evolved into a stable community
      identical to that in the adjacent aquifer but different from that in the
      uncontaminated area. At the contaminated location, bacteria with tmoA- and
      xylM/xylE1-like BTEX catabolic genotypes colonized the aquifer, while at the
      uncontaminated location only tmoA-like genotypes were detected. The communities
      in the mesocosms and in the aquifer adjacent to the wells in the contaminated
      area consisted mainly of Proteobacteria. At the uncontaminated location,
      Actinobacteria and Proteobacteria were found. Our results indicate that
      communities with long-term stability in their structures follow the contamination
      plume and rapidly colonize downstream areas upon contamination.

PMID- 16000794
TI  - Diversity of methanotrophic bacteria in tropical upland soils under different
      land uses.
AB  - Three upland soils from Thailand, a natural forest, a 16-year-old reforested
      site, and an agricultural field, were studied with regard to methane uptake and
      the community composition of methanotrophic bacteria (MB). The methane uptake
      rates were similar to rates described previously for forest and farmland soils of
      the temperate zone. The rates were lower at the agricultural site than at the
      native forest and reforested sites. The sites also differed in the MB community
      composition, which was characterized by denaturing gradient gel electrophoresis
      (DGGE) of pmoA gene fragments (coding for a subunit of particulate methane
      monooxygenase) that were PCR amplified from total soil DNA extracts. Cluster
      analysis based on the DGGE banding patterns indicated that the MB communities at
      the forested and reforested sites were similar to each other but different from
      that at the farmland site. Sequence analysis of excised DGGE bands indicated that
      Methylobacter spp. and Methylocystis spp. were present. Sequences of the "forest
      soil cluster" or "upland soil cluster alpha," which is postulated to represent
      organisms involved in atmospheric methane consumption in diverse soils, were
      detected only in samples from the native forest and reforested sites. Additional
      sequences that may represent uncultivated groups of MB in the Gammaproteobacteria
      were also detected.

PMID- 16000795
TI  - A multigene phylogenetic study of clonal diversity and divergence in North
      American strains of the plant pathogen Xylella fastidiosa.
AB  - Xylella fastidiosa is a pathogen that causes leaf scorch and related diseases in
      over 100 plant species, including Pierce's disease in grapevines (PD), phony
      peach disease (PP), plum leaf scald (PLS), and leaf scorch in almond (ALS), oak
      (OAK), and oleander (OLS). We used a high-resolution DNA sequence approach to
      investigate the evolutionary relationships, geographic variation, and divergence
      times among the X. fastidiosa isolates causing these diseases in North America.
      Using a large data set of 10 coding loci and 26 isolates, the phylogeny of X.
      fastidiosa defined three major clades. Two of these clades correspond to the
      recently identified X. fastidiosa subspecies piercei (PD and some ALS isolates)
      and X. fastidiosa subsp. multiplex (OAK, PP, PLS, and some ALS isolates). The
      third clade grouped all of the OLS isolates into a genetically distinct group,
      named X. fastidiosa subsp. sandyi. These well-differentiated clades indicate
      that, historically, X. fastidiosa has been a clonal organism. Based on their
      synonymous-site divergence ( approximately 3%), these three clades probably
      originated more than 15,000 years ago, long before the introduction of the
      nonnative plants that characterize most infections. The sister clades of X.
      fastidiosa subsp. sandyi and X. fastidiosa subsp. piercei have synonymous-site
      evolutionary rates 2.9 times faster than X. fastidiosa subsp. multiplex, possibly
      due to generation time differences. Within X. fastidiosa subsp. multiplex, a low
      level ( approximately 0.1%) of genetic differentiation indicates the recent
      divergence of ALS isolates from the PP, PLS, and OAK isolates due to host plant
      adaptation and/or allopatry. The low level of variation within the X. fastidiosa
      subsp. piercei and X. fastidiosa subsp. sandyi clades, despite their antiquity,
      suggests strong selection, possibly driven by host plant adaptation.

PMID- 16000796
TI  - Role for glycine betaine transport in Vibrio cholerae osmoadaptation and biofilm
      formation within microbial communities.
AB  - Vibrio cholerae is a halophilic facultative human pathogen found in marine and
      estuarine environments. Accumulation of compatible solutes is important for
      growth of V. cholerae at NaCl concentrations greater than 250 mM. We have
      identified and characterized two compatible solute transporters, OpuD and PutP,
      that are involved in uptake of glycine betaine and proline by V. cholerae. V.
      cholerae does not, however, possess the bet genes, suggesting that it is unable
      to synthesize glycine betaine. In contrast, many Vibrio species are able to
      synthesize glycine betaine from choline. It has been shown that many bacteria not
      only synthesize but also secrete glycine betaine. We hypothesized that sharing of
      compatible solutes might be a mechanism for cooperativity in microbial
      communities. In fact, we have demonstrated that, in high-osmolarity medium, V.
      cholerae growth and biofilm development are enhanced by supplementation with
      either glycine betaine or spent media from other bacterial species. Thus, we
      propose that compatible solutes provided by other microorganisms may contribute
      to survival of V. cholerae in the marine environment through facilitation of
      osmoadaptation and biofilm development.

PMID- 16000797
TI  - Environmental temperature controls Cryptosporidium oocyst metabolic rate and
      associated retention of infectivity.
AB  - Cryptosporidium is a significant cause of water-borne enteric disease throughout
      the world and represents a challenge to the water industry and a threat to public
      health. In this study we report the use of a cell culture-TaqMan PCR assay to
      measure oocyst inactivation rates in reagent-grade and environmental waters over
      a range of temperatures. While oocysts incubated at 4 degrees C and 15 degrees C
      remained infective over the 12-week holding period, we observed a 4 log(10)
      reduction in infectivity for both 20 and 25 degrees C incubation treatments at 12
      and 8 weeks, respectively, for all water types examined, a faster rate of
      inactivation for oocysts than previously reported. This temperature-dependent
      inactivation was further investigated using a simple and rapid ATP assay
      described herein. Time course experiments performed in reagent-grade water at
      incubation temperatures of 4, 15, 20, 25, 30, and 37 degrees C identified a close
      relationship between oocyst infectivity and oocyst ATP content, demonstrating
      that temperature inactivation at higher temperatures is a function of increased
      oocyst metabolic activity. While water quality did not affect oocyst
      inactivation, biological antagonism appears to be a key factor affecting oocyst
      removal from environmental waters. Both the cell culture-TaqMan PCR assay and the
      ATP assay provide a sensitive and quantitative method for the determination of
      environmental oocyst inactivation, providing an alternative to the more costly
      and time-consuming mouse infection assay. The findings presented here relating
      temperature to oocyst inactivation provide valuable information for determining
      the relative risks associated with Cryptosporidium oocysts in water.

PMID- 16000798
TI  - Characterization of citrate synthase from Geobacter sulfurreducens and evidence
      for a family of citrate synthases similar to those of eukaryotes throughout the
      Geobacteraceae.
AB  - Members of the family Geobacteraceae are commonly the predominant Fe(III)
      reducing microorganisms in sedimentary environments, as well as on the surface of
      energy-harvesting electrodes, and are able to effectively couple the oxidation of
      acetate to the reduction of external electron acceptors. Citrate synthase
      activity of these organisms is of interest due to its key role in acetate
      metabolism. Prior sequencing of the genome of Geobacter sulfurreducens revealed a
      putative citrate synthase sequence related to the citrate synthases of
      eukaryotes. All citrate synthase activity in G. sulfurreducens could be resolved
      to a single 49-kDa protein via affinity chromatography. The enzyme was
      successfully expressed at high levels in Escherichia coli with similar properties
      as the native enzyme, and kinetic parameters were comparable to related citrate
      synthases (kcat= 8.3 s(-1); Km= 14.1 and 4.3 microM for acetyl coenzyme A and
      oxaloacetate, respectively). The enzyme was dimeric and was slightly inhibited by
      ATP (Ki= 1.9 mM for acetyl coenzyme A), which is a known inhibitor for many
      eukaryotic, dimeric citrate synthases. NADH, an allosteric inhibitor of
      prokaryotic hexameric citrate synthases, did not affect enzyme activity. Unlike
      most prokaryotic dimeric citrate synthases, the enzyme did not have any
      methylcitrate synthase activity. A unique feature of the enzyme, in contrast to
      citrate synthases from both eukaryotes and prokaryotes, was a lack of stimulation
      by K+ ions. Similar citrate synthase sequences were detected in a diversity of
      other Geobacteraceae members. This first characterization of a eukaryotic-like
      citrate synthase from a prokaryote provides new insight into acetate metabolism
      in Geobacteraceae members and suggests a molecular target for tracking the
      presence and activity of these organisms in the environment.

PMID- 16000799
TI  - An internal reference technique for accurately quantifying specific mRNAs by real
      time PCR with application to the tceA reductive dehalogenase gene.
AB  - The accuracy of mRNA quantification by reverse transcription (RT) in conjunction
      with real-time PCR (qPCR) is limited by mRNA losses during sample preparation
      (cell lysis, RNA isolation, and DNA removal) and by inefficiencies in reverse
      transcription. To control for these losses and inefficiencies, a technique was
      developed that utilizes an exogenous internal reference mRNA (ref mRNA) along
      with mRNA absolute standard curves. The technique was applied to quantify mRNA of
      the trichloroethene (TCE) reductive dehalogenase-encoding tceA gene in an
      anaerobic TCE-to-ethene dechlorinating microbial enrichment. Compared to RT-qPCR
      protocols that utilize DNA absolute standard curves, application of the new
      technique increased measured quantities of tceA mRNA by threefold, demonstrating
      a substantial improvement in quantification. The technique was also effective for
      quantifying the loss of mRNA during specific steps of the sample processing
      protocol. Analysis revealed that the efficiency of the RNA isolation (56%) step
      was significantly less than that of the cell lysis (84%), DNA removal (93%), and
      RT (88%) steps. The technique was applied to compare the effects of cellular
      exposure to different chlorinated ethenes on tceA expression. Results show that
      exposure to TCE or cis-1,2-dichloroethene resulted in 25-fold-higher quantities
      of tceA mRNA than exposure to vinyl chloride or chlorinated ethene starvation.

PMID- 16000800
TI  - Effects of subtherapeutic administration of antimicrobial agents to beef cattle
      on the prevalence of antimicrobial resistance in Campylobacter jejuni and
      Campylobacter hyointestinalis.
AB  - The influence of antimicrobial agents on the development of antimicrobial
      resistance (AMR) in Campylobacter isolates recovered from 300 beef cattle
      maintained in an experimental feedlot was monitored over a 315-day period (11
      sample times). Groups of calves were assigned to one of the following
      antimicrobial treatments: chlortetracycline and sulfamethazine (CS),
      chlortetracycline alone (Ct), virginiamycin, monensin, tylosin phosphate, and no
      antimicrobial agent (i.e., control treatment). In total, 3,283 fecal samples were
      processed for campylobacters over the course of the experiment. Of the 2,052
      bacterial isolates recovered, 92% were Campylobacter (1,518 were Campylobacter
      hyointestinalis and 380 were C. jejuni). None of the antimicrobial treatments
      decreased the isolation frequency of C. jejuni relative to the control treatment.
      In contrast, C. hyointestinalis was isolated less frequently from animals treated
      with CS and to a lesser extent from animals treated with Ct. The majority (> or
      =94%) of C. jejuni isolates were sensitive to ampicillin, erythromycin, and
      ciprofloxacin, but more isolates with resistance to tetracycline were recovered
      from animals fed Ct. All of the 1,500 isolates of C. hyointestinalis examined
      were sensitive to ciprofloxacin. In contrast, 11%, 10%, and 1% of these isolates
      were resistant to tetracycline, erythromycin, and ampicillin, respectively. The
      number of animals from which C. hyointestinalis isolates with resistance to
      erythromycin and tetracycline were recovered differed among the antimicrobial
      treatments. Only Ct administration increased the carriage rates of erythromycin
      resistant isolates of C. hyointestinalis, and the inclusion of CS in the diet
      increased the number of animals from which tetracycline-resistant isolates were
      recovered. The majority of C. hyointestinalis isolates with resistance to
      tetracycline were obtained from cohorts within a single pen, and most of these
      isolates were recovered from cattle during feeding of a forage-based diet as
      opposed to a grain-based diet. The findings of this study show that the
      subtherapeutic administration of tetracycline, alone and in combination with
      sulfamethazine, to feedlot cattle can select for the carriage of resistant
      strains of Campylobacter species. Considering the widespread use of in-feed
      antimicrobial agents and the high frequency of beef cattle that shed
      campylobacters, the development of AMR should be monitored as part of an on-going
      surveillance program.

PMID- 16000801
TI  - Azo reductase activity of intact saccharomyces cerevisiae cells is dependent on
      the Fre1p component of plasma membrane ferric reductase.
AB  - Unspecific bacterial reduction of azo dyes is a process widely studied in
      correlation with the biological treatment of colored wastewaters, but the enzyme
      system associated with this bacterial capability has never been positively
      identified. Several ascomycete yeast strains display similar decolorizing
      behaviors. The yeast-mediated process requires an alternative carbon and energy
      source and is independent of previous exposure to the dyes. When substrate dyes
      are polar, their reduction is extracellular, strongly suggesting the involvement
      of an externally directed plasma membrane redox system. The present work
      demonstrates that, in Saccharomyces cerevisiae, the ferric reductase system
      participates in the extracellular reduction of azo dyes. The S. cerevisiae
      Deltafre1 and Deltafre1 Deltafre2 mutant strains, but not the Deltafre2 strain,
      showed much-reduced decolorizing capabilities. The FRE1 gene complemented the
      phenotype of S. cerevisiae Deltafre1 cells, restoring the ability to grow in
      medium without externally added iron and to decolorize the dye, following a
      pattern similar to the one observed in the wild-type strain. These results
      suggest that under the conditions tested, Fre1p is a major component of the azo
      reductase activity.

PMID- 16000802
TI  - Improved and versatile transformation system allowing multiple genetic
      manipulations of the hyperthermophilic archaeon Thermococcus kodakaraensis.
AB  - We have recently developed a gene disruption system for the hyperthermophilic
      archaeon Thermococcus kodakaraensis by utilizing a pyrF-deficient mutant, KU25,
      as a host strain and the pyrF gene as a selectable marker. To achieve multiple
      genetic manipulations for more advanced functional analyses of genes in vivo, it
      is necessary to establish multiple host-marker systems or to develop a system in
      which repeated utilization of one marker gene is possible. In this study, we
      first constructed a new host strain, KU216 (DeltapyrF), by specific and almost
      complete deletion of endogenous pyrF through homologous recombination. In this
      refined host, there is no need to consider unknown mutations caused by random
      mutagenesis, and unlike in the previous host, KU25, there is little, if any,
      possibility that unintended recombination between the marker gene and the
      chromosomal allele occurs. Furthermore, a new host-marker combination of a trpE
      deletant, KW128 (DeltapyrF DeltatrpE::pyrF), and the trpE gene was developed.
      This system made it possible to isolate transformants through a more simple
      selection procedure as well as to deduce the transformation efficiency,
      overcoming practical disadvantages of the first system. The effects of the
      transformation conditions were also investigated using this system. Finally, we
      have also established a system in which repeated utilization of the
      counterselectable pyrF marker is possible through its excision by pop-out
      recombination. Both endogenous and exogenous sequences could be applied as tandem
      repeats flanking the marker pyrF for pop-out recombination. A double deletion
      mutant, KUW1 (DeltapyrF DeltatrpE), constructed with the pop-out strategy, was
      demonstrated to be a useful host for the dual markers pyrF and trpE. Likewise, a
      triple deletion mutant, KUWH1 (DeltapyrF DeltatrpE DeltahisD), could also be
      constructed. The transformation systems developed here now provide the means for
      extensive genetic studies in this hyperthermophilic archaeon.

PMID- 16000803
TI  - Definition of genetically distinct attenuation mechanisms in naturally virulence
      attenuated Listeria monocytogenes by comparative cell culture and molecular
      characterization.
AB  - Listeria monocytogenes is a foodborne pathogen able to cause serious disease in
      humans and animals. Not all isolates are equally pathogenic, however, and several
      isolates have been characterized as naturally virulence attenuated. We sought to
      identify the genetic basis of natural virulence attenuation using cell culture
      assays and molecular techniques. By comparing the phenotypes of naturally
      virulence-attenuated isolates to those of defined virulence gene mutants in
      plaque, cytotoxicity, and hemolysis assays and by characterizing selected
      virulence genes and their expression using DNA sequencing and TaqMan reverse
      transcriptase PCR, we classified virulence-attenuated isolates into four
      categories. Both group A and group B isolates were noncytotoxic and nonhemolytic;
      however, group A isolates underexpressed listeriolysin O (LLO, encoded by hlyA),
      while group B isolates produced LLO proteins that were inactive. The single
      isolate in group C was fully cytotoxic, had higher than wild-type hemolytic
      activity, and was, therefore, likely virulence attenuated due to overexpression
      of LLO. Group D isolates were characterized by normal cytotoxicity, hemolytic
      activity, and hlyA expression but had reduced intracellular growth. The genetic
      mechanisms causing virulence-attenuated phenotypes among the group D isolates
      could not be determined definitively but may involve defects in the expression of
      actA or the function of the ActA protein. Our results show (i) that the
      combination of cell culture assays and molecular techniques used in this study
      allows for identification and characterization of naturally virulence-attenuated
      isolates and (ii) that multiple distinct genetic mechanisms are responsible for
      natural virulence attenuation in L. monocytogenes.

PMID- 16000804
TI  - Quantitative detection of Clostridium perfringens in the broiler fowl
      gastrointestinal tract by real-time PCR.
AB  - Strains of Clostridium perfringens are a frequent cause of food-borne disease and
      gas gangrene and are also associated with necrotic enteritis in chickens. To
      detect and quantify the levels of C. perfringens in the chicken gastrointestinal
      tract, a quantitative real-time PCR assay utilizing a fluorogenic, hydrolysis
      type probe was developed and utilized to assay material retrieved from the
      broiler chicken cecum and ileum. Primers and probe were selected following an
      alignment of 16S rDNA sequences from members of cluster I of the genus
      Clostridium, and proved to be specific for C. perfringens. The assay could detect
      approximately 50 fg of C. perfringens genomic DNA and approximately 20 cells in
      pure culture. Measurements of the analytical sensitivity determined with spiked
      intestinal contents indicated that the consistent limit of detection with ileal
      samples was approximately 10(2) CFU/g of ileal material, but only about 10(4)
      CFU/g of cecal samples. The decreased sensitivity with the cecal samples was due
      to the presence of an unidentified chemical PCR inhibitor(s) in the cecal DNA
      purifications. The assay was utilized to rapidly detect and quantify C.
      perfringens levels in the gut tract of broiler chickens reared without
      supplementary growth-promoting antibiotics that manifested symptoms of necrotic
      enteritis. The results illustrated that quantitative real-time PCR correlates
      well with quantification via standard plate counts in samples taken from the
      ileal region of the gastrointestinal tract.

PMID- 16000805
TI  - Development of a recA gene-based identification approach for the entire
      Burkholderia genus.
AB  - Burkholderia is an important bacterial genus containing species of ecological,
      biotechnological, and pathogenic interest. With their taxonomy undergoing
      constant revision and the phenotypic similarity of several species, correct
      identification of Burkholderia is difficult. A genetic scheme based on the recA
      gene has greatly enhanced the identification of Burkholderia cepacia complex
      species. However, the PCR developed for the latter approach was limited by its
      specificity for the complex. By alignment of existing and novel Burkholderia recA
      sequences, we designed new PCR primers and evaluated their specificity by testing
      a representative panel of Burkholderia strains. PCR followed by restriction
      fragment length polymorphism analysis of an 869-bp portion of the Burkholderia
      recA gene was not sufficiently discriminatory. Nucleotide sequencing followed by
      phylogenetic analysis of this recA fragment differentiated both putative and
      known Burkholderia species and all members of the B. cepacia complex. In
      addition, it enabled the design of a Burkholderia genus-specific recA PCR that
      produced a 385-bp amplicon, the sequence of which was also able to discriminate
      all species examined. Phylogenetic analysis of 188 novel recA genes enabled
      clarification of the taxonomic position of several important Burkholderia strains
      and revealed the presence of four novel B. cepacia complex recA lineages.
      Although the recA phylogeny could not be used as a means to differentiate B.
      cepacia complex strains recovered from clinical infection versus the natural
      environment, it did facilitate the identification of clonal strain types of B.
      cepacia, B. stabilis, and B. ambifaria capable of residing in both niches.

PMID- 16000806
TI  - Reduction of perchlorate and nitrate by microbial communities in vadose soil.
AB  - Perchlorate contamination is a concern because of the increasing frequency of its
      detection in soils and groundwater and its presumed inhibitory effect on human
      thyroid hormone production. Although significant perchlorate contamination occurs
      in the vadose (unsaturated) zone, little is known about perchlorate
      biodegradation potential by indigenous microorganisms in these soils. We measured
      the effects of electron donor (acetate and hydrogen) and nitrate addition on
      perchlorate reduction rates and microbial community composition in microcosm
      incubations of vadose soil. Acetate and hydrogen addition enhanced perchlorate
      reduction, and a longer lag period was observed for hydrogen (41 days) than for
      acetate (14 days). Initially, nitrate suppressed perchlorate reduction, but once
      perchlorate started to be degraded, the process was stimulated by nitrate.
      Changes in the bacterial community composition were observed in microcosms
      enriched with perchlorate and either acetate or hydrogen. Denaturing gradient gel
      electrophoresis analysis and partial sequencing of 16S rRNA genes recovered from
      these microcosms indicated that formerly reported perchlorate-reducing bacteria
      were present in the soil and that microbial community compositions were different
      between acetate- and hydrogen-amended microcosms. These results indicate that
      there is potential for perchlorate bioremediation by native microbial communities
      in vadose soil.

PMID- 16000807
TI  - Evaluation of lateral-flow Clostridium botulinum neurotoxin detection kits for
      food analysis.
AB  - The suitability and sensitivity of two in vitro lateral-flow assays for detecting
      Clostridium botulinum neurotoxins (BoNTs) in an assortment of foods were
      evaluated. Toxin extraction and preparation methods for various liquid, solid,
      and high-fat-content foods were developed. The lateral-flow assays, one developed
      by the Naval Medical Research Center (Silver Spring, MD) and the other by
      Alexeter Technologies (Gaithersburg, MD), are based on the immunodetection of
      BoNT types A, B, and E. The assays were found to be rapid and easy to perform
      with minimum requirements for laboratory equipment or skills. They can readily
      detect 10 ng/ml of BoNT types A and B and 20 ng/ml of BoNT type E. Compared to
      other in vitro detection methods, these assays are less sensitive, and the
      assessment of a result is strictly qualitative. However, the assay was found to
      be simple to use and to require minimal training. The assays successfully
      detected BoNT types A, B, and E in a wide variety of foods, suggesting their
      potential usefulness as a preliminary screening system for triaging food samples
      with elevated BoNT levels in the event of a C. botulinum contamination event.

PMID- 16000808
TI  - Highly hydrolytic reuteransucrase from probiotic Lactobacillus reuteri strain
      ATCC 55730.
AB  - Lactobacillus reuteri strain ATCC 55730 (LB BIO) was isolated as a pure culture
      from a Reuteri tablet purchased from the BioGaia company. This probiotic strain
      produces a soluble glucan (reuteran), in which the majority of the linkages are
      of the alpha-(1-->4) glucosidic type ( approximately 70%). This reuteran also
      contains alpha-(1-->6)- linked glucosyl units and 4,6-disubstituted alpha
      glucosyl units at the branching points. The LB BIO glucansucrase gene (gtfO) was
      cloned and expressed in Escherichia coli, and the GTFO enzyme was purified. The
      recombinant GTFO enzyme and the LB BIO culture supernatants synthesized identical
      glucan polymers with respect to linkage type and size distribution. GTFO thus is
      a reuteransucrase, responsible for synthesis of this reuteran polymer in LB BIO.
      The preference of GTFO for synthesizing alpha-(1-->4) linkages is also evident
      from the oligosaccharides produced from sucrose with different acceptor
      substrates, e.g., isopanose from isomaltose. GTFO has a relatively high
      hydrolysis/transferase activity ratio. Complete conversion of 100 mM sucrose by
      GTFO nevertheless yielded large amounts of reuteran, although more than 50% of
      sucrose was converted into glucose. This is only the second example of the
      isolation and characterization of a reuteransucrase and its reuteran product,
      both found in different L. reuteri strains. GTFO synthesizes a reuteran with the
      highest amount of alpha-(1-->4) linkages reported to date.

PMID- 16000809
TI  - Cloning and expression of islandisin, a new thermostable subtilisin from
      Fervidobacterium islandicum, in Escherichia coli.
AB  - A gene encoding a subtilisin-like protease, designated islandisin, from the
      extremely thermophilic bacterium Fervidobacterium islandicum (DSMZ 5733) was
      cloned and actively expressed in Escherichia coli. The gene was identified by PCR
      using degenerated primers based on conserved regions around two of the three
      catalytic residues (Asp, His, and Ser) of subtilisin-like serine protease
      encoding genes. Using inverse PCR regions flanking the catalytic residues, the
      gene could be cloned. Sequencing revealed an open reading frame of 2,106 bp. The
      deduced amino acid sequence indicated that the enzyme is synthesized as a
      proenzyme with a putative signal sequence of 33 amino acids (aa) in length. The
      mature protein contains the three catalytic residues (Asp177, His215, and Ser391)
      and has a length of 668 aa. Amino acid sequence comparison and phylogenetic
      analysis indicated that this enzyme could be classified as a subtilisin-like
      serine protease in the subgroup of thermitase. The whole gene was amplified by
      PCR, ligated into pET-15b, and successfully expressed in E. coli BL21(DE3)pLysS.
      The recombinant islandisin was purified by heat denaturation, followed by
      hydroxyapatite chromatography. The enzyme is active at a broad range of
      temperatures (60 to 80 degrees C) and pHs (pH 6 to 8.5) and shows optimal
      proteolytic activity at 80 degrees C and pH 8.0. Islandisin is resistant to a
      number of detergents and solvents and shows high thermostability over a long
      period of time (up to 32 h) at 80 degrees C with a half-life of 4 h at 90 degrees
      C and 1.5 h at 100 degrees C.

PMID- 16000810
TI  - Improvement of the fungal biocontrol agent Trichoderma atroviride to enhance both
      antagonism and induction of plant systemic disease resistance.
AB  - Biocontrol agents generally do not perform well enough under field conditions to
      compete with chemical fungicides. We determined whether transgenic strain SJ3-4
      of Trichoderma atroviride, which expresses the Aspergillus niger glucose oxidase
      encoding gene, goxA, under a homologous chitinase (nag1) promoter had increased
      capabilities as a fungal biocontrol agent. The transgenic strain differed only
      slightly from the wild-type in sporulation or the growth rate. goxA expression
      occurred immediately after contact with the plant pathogen, and the glucose
      oxidase formed was secreted. SJ3-4 had significantly less N-acetylglucosaminidase
      and endochitinase activities than its nontransformed parent. Glucose oxidase
      containing culture filtrates exhibited threefold-greater inhibition of
      germination of spores of Botrytis cinerea. The transgenic strain also more
      quickly overgrew and lysed the plant pathogens Rhizoctonia solani and Pythium
      ultimum. In planta, SJ3-4 had no detectable improved effect against low inoculum
      levels of these pathogens. Beans planted in heavily infested soil and treated
      with conidia of the transgenic Trichoderma strain germinated, but beans treated
      with wild-type spores did not germinate. SJ3-4 also was more effective in
      inducing systemic resistance in plants. Beans with SJ3-4 root protection were
      highly resistant to leaf lesions caused by the foliar pathogen B. cinerea. This
      work demonstrates that heterologous genes driven by pathogen-inducible promoters
      can increase the biocontrol and systemic resistance-inducing properties of fungal
      biocontrol agents, such as Trichoderma spp., and that these microbes can be used
      as vectors to provide plants with useful molecules (e.g., glucose oxidase) that
      can increase their resistance to pathogens.

PMID- 16000811
TI  - Location of the Bombyx mori aminopeptidase N type 1 binding site on Bacillus
      thuringiensis Cry1Aa toxin.
AB  - We analyzed the binding site on Cry1Aa toxin for the Cry1Aa receptor in Bombyx
      mori, 115-kDa aminopeptidase N type 1 (BmAPN1) (K. Nakanishi, K. Yaoi, Y. Nagino,
      H. Hara, M. Kitami, S. Atsumi, N. Miura, and R. Sato, FEBS Lett. 519:215-220,
      2002), by using monoclonal antibodies (MAbs) that block binding between the
      binding site and the receptor. First, we produced a series of MAbs against Cry1Aa
      and obtained two MAbs, MAbs 2C2 and 1B10, that were capable of blocking the
      binding between Cry1Aa and BmAPN1 (blocking MAbs). The epitope of the Fab
      fragments of MAb 2C2 overlapped the BmAPN1 binding site, whereas the epitope of
      the Fab fragments of MAb 1B10 did not overlap but was located close to the
      binding site. Using three approaches for epitope mapping, we identified two
      candidate epitopes for the blocking MAbs on Cry1Aa. We constructed two Cry1Aa
      toxin mutants by substituting a cysteine on the toxin surface at each of the two
      candidate epitopes, and the small blocking molecule N-(9-acridinyl)maleimide
      (NAM) was introduced at each cysteine substitution to determine the true epitope.
      The Cry1Aa mutant with NAM bound to Cys582 did not bind either of the two
      blocking MAbs, suggesting that the true epitope for each of the blocking MAbs was
      located at the site containing Val582, which also consisted of 508STLRVN513 and
      582VFTLSAHV589. These results indicated that the BmAPN1 binding site overlapped
      part of the region blocked by MAb 2C2 that was close to but excluded the actual
      epitope of MAb 2C2 on domain III of Cry1Aa toxin. We also discuss another area on
      Cry1Aa toxin as a new candidate site for BmAPN1 binding.

PMID- 16000812
TI  - Diel variations in carbon metabolism by green nonsulfur-like bacteria in alkaline
      siliceous hot spring microbial mats from Yellowstone National Park.
AB  - Green nonsulfur-like bacteria (GNSLB) in hot spring microbial mats are thought to
      be mainly photoheterotrophic, using cyanobacterial metabolites as carbon sources.
      However, the stable carbon isotopic composition of typical Chloroflexus and
      Roseiflexus lipids suggests photoautotrophic metabolism of GNSLB. One possible
      explanation for this apparent discrepancy might be that GNSLB fix inorganic
      carbon only during certain times of the day. In order to study temporal
      variability in carbon metabolism by GNSLB, labeling experiments with
      [13C]bicarbonate, [14C]bicarbonate, and [13C]acetate were performed during
      different times of the day. [14C]bicarbonate labeling indicated that during the
      morning, incorporation of label was light dependent and that both cyanobacteria
      and GNSLB were involved in bicarbonate uptake. 13C-labeling experiments indicated
      that during the morning, GNSLB incorporated labeled bicarbonate at least to the
      same degree as cyanobacteria. The incorporation of [13C]bicarbonate into specific
      lipids could be stimulated by the addition of sulfide or hydrogen, which both
      were present in the morning photic zone. The results suggest that GNSLB have the
      potential for photoautotrophic metabolism during low-light periods. In high-light
      periods, inorganic carbon was incorporated primarily into Cyanobacteria-specific
      lipids. The results of a pulse-labeling experiment were consistent with overnight
      transfer of label to GNSLB, which could be interrupted by the addition of
      unlabeled acetate and glycolate. In addition, we observed direct incorporation of
      [13C]acetate into GNSLB lipids in the morning. This suggests that GNSLB also have
      a potential for photoheterotrophy in situ.

PMID- 16000813
TI  - Fate of 14C-labeled microbial products derived from nitrifying bacteria in
      autotrophic nitrifying biofilms.
AB  - The cross-feeding of microbial products derived from 14C-labeled nitrifying
      bacteria to heterotrophic bacteria coexisting in an autotrophic nitrifying
      biofilm was quantitatively analyzed by using microautoradiography combined with
      fluorescence in situ hybridization (MAR-FISH). After only nitrifying bacteria
      were labeled with [14C]bicarbonate, biofilm samples were incubated with and
      without NH4+ as a sole energy source for 10 days. The transfer of 14C originally
      incorporated into nitrifying bacterial cells to heterotrophic bacteria was
      monitored with time by using MAR-FISH. The MAR-FISH analysis revealed that most
      phylogenetic groups of heterotrophic bacteria except the beta-Proteobacteria
      showed significant uptake of 14C-labeled microbial products. In particular, the
      members of the Chloroflexi were strongly MAR positive in the culture without NH4+
      addition, in which nitrifying bacteria tended to decay. This indicated that the
      members of the Chloroflexi preferentially utilized microbial products derived
      from mainly biomass decay. On the other hand, the members of the Cytophaga
      Flavobacterium cluster gradually utilized 14C-labeled products in the culture
      with NH4+ addition in which nitrifying bacteria grew. This result suggested that
      these bacteria preferentially utilized substrate utilization-associated products
      of nitrifying bacteria and/or secondary metabolites of 14C-labeled structural
      cell components. Our results clearly demonstrated that the coexisting
      heterotrophic bacteria efficiently degraded and utilized dead biomass and
      metabolites of nitrifying bacteria, which consequently prevented accumulation of
      organic waste products in the biofilm.

PMID- 16000814
TI  - Protein engineering of epoxide hydrolase from Agrobacterium radiobacter AD1 for
      enhanced activity and enantioselective production of (R)-1-phenylethane-1,2-diol.
AB  - DNA shuffling and saturation mutagenesis of positions F108, L190, I219, D235, and
      C248 were used to generate variants of the epoxide hydrolase of Agrobacterium
      radiobacter AD1 (EchA) with enhanced enantioselectivity and activity for styrene
      oxide and enhanced activity for 1,2-epoxyhexane and epoxypropane. EchA variant
      I219F has more than fivefold-enhanced enantioselectivity toward racemic styrene
      oxide, with the enantiomeric ratio value (E value) for the production of (R)-1
      phenylethane-1,2-diol increased from 17 for the wild-type enzyme to 91, as well
      as twofold-improved activity for the production of (R)-1-phenylethane-1,2-diol
      (1.96 +/- 0.09 versus 1.04 +/- 0.07 micromol/min/mg for wild-type EchA). Computer
      modeling indicated that this mutation significantly alters (R)-styrene oxide
      binding in the active site. Another three variants from EchA active-site
      engineering, F108L/C248I, I219L/C248I, and F108L/I219L/C248I, also exhibited
      improved enantioselectivity toward racemic styrene oxide in favor of production
      of the corresponding diol in the (R) configuration (twofold enhancement in their
      E values). Variant F108L/I219L/C248I also demonstrated 10-fold- and 2-fold
      increased activity on 5 mM epoxypropane (24 +/- 2 versus 2.4 +/- 0.3
      micromol/min/mg for the wild-type enzyme) and 5 mM 1,2-epoxyhexane (5.2 +/- 0.5
      versus 2.6 +/- 0.0 micromol/min/mg for the wild-type enzyme). Both variants L190F
      (isolated from a DNA shuffling library) and L190Y (created from subsequent
      saturation mutagenesis) showed significantly enhanced activity for racemic
      styrene oxide hydrolysis, with 4.8-fold (8.6 +/- 0.3 versus 1.8 +/- 0.2
      micromol/min/mg for the wild-type enzyme) and 2.7-fold (4.8 +/- 0.8 versus 1.8 +/
      0.2 micromol/min/mg for the wild-type enzyme) improvements, respectively. L190Y
      also hydrolyzed 1,2-epoxyhexane 2.5 times faster than the wild-type enzyme.

PMID- 16000815
TI  - Development and application of an insertional system for gene delivery and
      expression in Campylobacter jejuni.
AB  - The genetic investigation of Campylobacter jejuni, an important gastrointestinal
      pathogen, has been hampered by the lack of an efficient system for introduction
      of exogenous genetic information, as commonly used vectors designed for
      Escherichia coli and other bacteria cannot be maintained in Campylobacter cells.
      Additionally, gene expression in Campylobacter requires the presence of species
      specific promoters. In this study we exploited the availability of several
      conserved copies of rRNA gene clusters for insertion of various genes into the
      chromosome by homologous recombination. The high conservation of the rRNA
      sequences means that the procedure can be applied to other Campylobacter strains.
      The presence of a Campylobacter-derived promoter in this vector ensures
      expression of exogenous genes in target cells. The efficiency of the procedure
      was demonstrated by complementation of mutations in two strains of Campylobacter.
      In addition, we applied the system for introduction and expression of a green
      fluorescent protein (GFP). GFP-expressing Campylobacter allowed visualization of
      sessile bacteria attached to a glass surface in stationary liquid culture. The
      study demonstrated that the attached bacteria contained an assemblage of coccoid
      and spiral forms with liquid channels preserving viable highly motile cells. We
      demonstrate a novel universal procedure for gene delivery and expression that can
      be used as an efficient tool to study this poorly understood pathogen. The
      principles developed in this study could be more widely applied for the
      manipulation of other bacteria that are refractory to genetic analysis.

PMID- 16000816
TI  - Determination of spatial distributions of zinc and active biomass in microbial
      biofilms by two-photon laser scanning microscopy.
AB  - The spatial distributions of zinc, a representative transition metal, and active
      biomass in bacterial biofilms were determined using two-photon laser scanning
      microscopy (2P-LSM). Application of 2P-LSM permits analysis of thicker biofilms
      than are amenable to observation with confocal laser scanning microscopy and also
      provides selective excitation of a smaller focal volume with greater depth
      localization. Thin Escherichia coli PHL628 biofilms were grown in a minimal
      mineral salts medium using pyruvate as the carbon and energy source under batch
      conditions, and thick biofilms were grown in Luria-Bertani medium using a
      continuous-flow drip system. The biofilms were visualized by 2P-LSM and shown to
      have heterogeneous structures with dispersed dense cell clusters, rough surfaces,
      and void spaces. Contrary to homogeneous biofilm model predictions that active
      biomass would be located predominantly in the outer regions of the biofilm and
      inactive or dead biomass (biomass debris) in the inner regions, significant
      active biomass fractions were observed at all depths in biofilms (up to 350
      microm) using live/dead fluorescent stains. The active fractions were dependent
      on biofilm thickness and are attributed to the heterogeneous characteristics of
      biofilm structures. A zinc-binding fluorochrome (8-hydroxy-5
      dimethylsulfoamidoquinoline) was synthesized and used to visualize the spatial
      location of added Zn within biofilms. Zn was distributed evenly in a thin (12
      microm) biofilm but was located only at the surface of thick biofilms,
      penetrating less than 20 microm after 1 h of exposure. The relatively slow
      movement of Zn into deeper biofilm layers provides direct evidence in support of
      the concept that thick biofilms may confer resistance to toxic metal species by
      binding metals at the biofilm-bulk liquid interface, thereby retarding metal
      diffusion into the biofilm (G. M. Teitzel and M. R. Park, Appl. Environ.
      Microbiol. 69:2313-2320, 2003).

PMID- 16000817
TI  - Differential gene expression for investigation of Escherichia coli biofilm
      inhibition by plant extract ursolic acid.
AB  - After 13,000 samples of compounds purified from plants were screened, a new
      biofilm inhibitor, ursolic acid, has been discovered and identified. Using both
      96-well microtiter plates and a continuous flow chamber with COMSTAT analysis, 10
      microg of ursolic acid/ml inhibited Escherichia coli biofilm formation 6- to 20
      fold when added upon inoculation and when added to a 24-h biofilm; however,
      ursolic acid was not toxic to E. coli, Pseudomonas aeruginosa, Vibrio harveyi,
      and hepatocytes. Similarly, 10 microg of ursolic acid/ml inhibited biofilm
      formation by >87% for P. aeruginosa in both complex and minimal medium and by 57%
      for V. harveyi in minimal medium. To investigate the mechanism of this nontoxic
      inhibition on a global genetic basis, DNA microarrays were used to study the gene
      expression profiles of E. coli K-12 grown with or without ursolic acid. Ursolic
      acid at 10 and 30 microg/ml induced significantly (P < 0.05) 32 and 61 genes,
      respectively, and 19 genes were consistently induced. The consistently induced
      genes have functions for chemotaxis and mobility (cheA, tap, tar, and motAB),
      heat shock response (hslSTV and mopAB), and unknown functions (such as b1566 and
      yrfHI). There were 31 and 17 genes repressed by 10 and 30 microg of ursolic
      acid/ml, respectively, and 12 genes were consistently repressed that have
      functions in cysteine synthesis (cysK) and sulfur metabolism (cysD), as well as
      unknown functions (such as hdeAB and yhaDFG). Ursolic acid inhibited biofilms
      without interfering with quorum sensing, as shown with the V. harveyi AI-1 and AI
      2 reporter systems. As predicted by the differential gene expression, deleting
      motAB counteracts ursolic acid inhibition (the paralyzed cells no longer become
      too motile). Based on the differential gene expression, it was also discovered
      that sulfur metabolism (through cysB) affects biofilm formation (in the absence
      of ursolic acid).

PMID- 16000818
TI  - Gut symbiotic bacteria of the genus Burkholderia in the broad-headed bugs
      Riptortus clavatus and Leptocorisa chinensis (Heteroptera: Alydidae).
AB  - The Japanese common broad-headed bugs Riptortus clavatus and Leptocorisa
      chinensis possess a number of crypts in the posterior region of the midgut, whose
      lumen contains a copious amount of bacterial cells. We characterized the gut
      symbiotic bacteria by using molecular phylogenetic analysis, light and electron
      microscopy, in situ hybridization, and PCR-based detection techniques.
      Restriction fragment length polymorphism analysis of 16S rRNA gene clones
      suggested that a single bacterium dominated the microbiota in the crypts of the
      both bug species. The predominant 16S rRNA gene sequences obtained from different
      individuals and species of the bugs were not identical but were very similar to
      each other. Homology searches in the DNA databases revealed that the sequences
      showed the highest levels of similarity (96% to 99%) to the sequences of
      Burkholderia spp. belonging to the beta subdivision of the class Proteobacteria.
      In situ hybridization with specific oligonucleotide probes confirmed the
      localization of the Burkholderia symbiont in the lumen of the midgut crypts.
      Electron microscopy showed that the lumen of the crypts was filled with rod
      shaped bacteria of a single morphotype. Molecular phylogenetic analysis
      demonstrated that the Burkholderia symbionts of the bugs formed a well-defined
      monophyletic group, although the group also contained several environmental
      Burkholderia strains. The phylogenetic relationship of the Burkholderia symbionts
      did not reflect the relationship of the host bug species at all. The sequences
      from R. clavatus and the sequences from L. chinensis did not form clades but were
      intermingled in the phylogeny, suggesting that horizontal transmission of the
      symbiont might have occasionally occurred between populations and species of the
      bugs.

PMID- 16000819
TI  - Susceptibility of biofilms to Bdellovibrio bacteriovorus attack.
AB  - Biofilms are communities of microorganisms attached to a surface, and the growth
      of these surface attached communities is thought to provide microorganisms with
      protection against a range of biotic and abiotic agents. The capability of the
      gram-negative predatory bacterium Bdellovibrio bacteriovorus to control and
      reduce an existing Escherichia coli biofilm was evaluated in a static assay. A
      reduction in biofilm biomass was observed as early as 3 h after exposure to the
      predator, and an 87% reduction in crystal violet staining corresponding to a 4
      log reduction in biofilm cell viability was seen after a 24-h exposure period. We
      observed that an initial titer of Bdellovibrio as low as 10(2) PFU/well or an
      exposure to the predator as short as 30 min is sufficient to reduce a preformed
      biofilm. The ability of B. bacteriovorus to reduce an existing biofilm was
      confirmed by scanning electron microscopy. The reduction in biofilm biomass
      obtained after the first 24 h of exposure to the predator remained unchanged even
      after longer exposure periods and reinoculation of the samples with fresh
      Bdellovibrio; however, no genetically stable resistant population of the host
      bacteria could be detected. Our data suggest that growth in a biofilm does not
      prevent predation by Bdellovibrio but allows a level of survival from attack
      greater than that observed for planktonic cells. In flow cell experiments B.
      bacteriovorus was able to decrease the biomass of both E. coli and Pseudomonas
      fluorescens biofilms as determined by phase-contrast and epifluorescence
      microscopy.

PMID- 16000820
TI  - Mediterranean fruit fly as a potential vector of bacterial pathogens.
AB  - The Mediterranean fruit fly (Ceratitis capitata) is a cosmopolitan pest of
      hundreds of species of commercial and wild fruits. It is considered a major
      economic pest of commercial fruits in the world. Adult Mediterranean fruit flies
      feed on all sorts of protein sources, including animal excreta, in order to
      develop eggs. After reaching sexual maturity and copulating, female flies lay
      eggs in fruit by puncturing the skin with their ovipositors and injecting batches
      of eggs into the wounds. In view of the increase in food-borne illnesses
      associated with consumption of fresh produce and unpasteurized fruit juices, we
      investigated the potential of Mediterranean fruit fly to serve as a vector for
      transmission of human pathogens to fruits. Addition of green fluorescent protein
      (GFP)-tagged Escherichia coli to a Mediterranean fruit fly feeding solution
      resulted in a dose-dependent increase in the fly's bacterial load. Flies exposed
      to fecal material enriched with GFP-tagged E. coli were similarly contaminated
      and were capable of transmitting E. coli to intact apples in a cage model system.
      Washing contaminated apples with tap water did not eliminate the E. coli. Flies
      inoculated with E. coli harbored the bacteria for up to 7 days following
      contamination. Fluorescence microscopy demonstrated that the majority of
      fluorescent bacteria were confined along the pseudotrachea in the labelum edge of
      the fly proboscis. Wild flies captured at various geographic locations were found
      to carry coliforms, and in some cases presumptive identification of E. coli was
      made. These findings support the hypothesis that the common Mediterranean fruit
      fly is a potential vector of human pathogens to fruits.

PMID- 16000821
TI  - Genomic organization and molecular analysis of virulent bacteriophage 2972
      infecting an exopolysaccharide-producing Streptococcus thermophilus strain.
AB  - The Streptococcus thermophilus virulent pac-type phage 2972 was isolated from a
      yogurt made in France in 1999. It is a representative of several phages that have
      emerged with the industrial use of the exopolysaccharide-producing S.
      thermophilus strain RD534. The genome of phage 2972 has 34,704 bp with an overall
      G+C content of 40.15%, making it the shortest S. thermophilus phage genome
      analyzed so far. Forty-four open reading frames (ORFs) encoding putative proteins
      of 40 or more amino acids were identified, and bioinformatic analyses led to the
      assignment of putative functions to 23 ORFs. Comparative genomic analysis of
      phage 2972 with the six other sequenced S. thermophilus phage genomes confirmed
      that the replication module is conserved and that cos- and pac-type phages have
      distinct structural and packaging genes. Two group I introns were identified in
      the genome of 2972. They interrupted the genes coding for the putative endolysin
      and the terminase large subunit. Phage mRNA splicing was demonstrated for both
      introns, and the secondary structures were predicted. Eight structural proteins
      were also identified by N-terminal sequencing and/or matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry. Detailed analysis of the
      putative minor tail proteins ORF19 and ORF21 as well as the putative receptor
      binding protein ORF20 showed the following interesting features: (i) ORF19 is a
      hybrid protein, because it displays significant identity with both pac- and cos
      type phages; (ii) ORF20 is unique; and (iii) a protein similar to ORF21 of 2972
      was also found in the structure of the cos-type phage DT1, indicating that this
      structural protein is present in both S. thermophilus phage groups. The
      implications of these findings for phage classification are discussed.

PMID- 16000822
TI  - Rickettsia symbiont in the pea aphid Acyrthosiphon pisum: novel cellular tropism,
      effect on host fitness, and interaction with the essential symbiont Buchnera.
AB  - In natural populations of the pea aphid Acyrthosiphon pisum, a facultative
      bacterial symbiont of the genus Rickettsia has been detected at considerable
      infection frequencies worldwide. We investigated the effects of the Rickettsia
      symbiont on the host aphid and also on the coexisting essential symbiont
      Buchnera. In situ hybridization revealed that the Rickettsia symbiont was
      specifically localized in two types of host cells specialized for endosymbiosis:
      secondary mycetocytes and sheath cells. Electron microscopy identified bacterial
      rods, about 2 mum long and 0.5 mum thick, in sheath cells of Rickettsia-infected
      aphids. Virus-like particles were sometimes observed in association with the
      bacterial cells. By an antibiotic treatment, we generated Rickettsia-infected and
      Rickettsia-eliminated aphid strains with an identical genetic background.
      Comparison of these strains revealed that Rickettsia infection negatively
      affected some components of the host fitness. Quantitative PCR analysis of the
      bacterial population dynamics identified a remarkable interaction between the
      coexisting symbionts: Buchnera population was significantly suppressed in the
      presence of Rickettsia, particularly at the young adult stage, when the aphid
      most actively reproduces. On the basis of these results, we discussed the
      possible mechanisms that enable the prevalence of Rickettsia infection in natural
      host populations in spite of the negative fitness effects observed in the
      laboratory.

PMID- 16000823
TI  - Identity and ecophysiology of uncultured actinobacterial polyphosphate
      accumulating organisms in full-scale enhanced biological phosphorus removal
      plants.
AB  - Microautoradiography combined with fluorescence in situ hybridization (MAR-FISH)
      was used to screen for potential polyphosphate-accumulating organisms (PAO) in a
      full-scale enhanced biological phosphorus removal (EBPR) plant. The results
      showed that, in addition to uncultured Rhodocyclus-related PAO, two morphotypes
      hybridizing with gene probes for the gram-positive Actinobacteria were also
      actively involved in uptake of orthophosphate (Pi). Clone library analysis and
      further investigations by MAR-FISH using two new oligonucleotide probes revealed
      that both morphotypes, cocci in clusters of tetrads and short rods in clumps,
      were relatively closely related to the genus Tetrasphaera within the family
      Intrasporangiaceae of the Actinobacteria (93 to 98% similarity in their 16S rRNA
      genes). FISH analysis of the community biomass in the treatment plant
      investigated showed that the short rods (targeted by probe Actino-658) were the
      most abundant (12% of all Bacteria hybridizing with general bacterial probes),
      while the cocci in tetrads (targeted by probe Actino-221) made up 7%. Both
      morphotypes took up P(i) aerobically only if, in a previous anaerobic phase, they
      had taken up organic matter from wastewater or a mixture of amino acids. They
      could not take up short-chain fatty acids (e.g., acetate), glucose, or ethanol
      under anaerobic or aerobic conditions. The storage compound produced during the
      anaerobic period was not polyhydroxyalkanoates, as for Rhodocyclus-related PAO,
      and its identity is still unknown. Growth and uptake of Pi took place in the
      presence of oxygen and nitrate but not nitrite, indicating a lack of denitrifying
      ability. A survey of the occurrence of these actinobacterial PAO in 10 full-scale
      EBPR plants revealed that both morphotypes were widely present, and in several
      plants more abundant than the Rhodocyclus-related PAO, thus playing a very
      important role in the EBPR process.

PMID- 16000824
TI  - Rapid method for enumeration of viable Legionella pneumophila and other
      Legionella spp. in water.
AB  - A sensitive and specific method has been developed to enumerate viable L.
      pneumophila and other Legionella spp. in water by epifluorescence microscopy in a
      short period of time (a few hours). This method allows the quantification of L.
      pneumophila or other Legionella spp. as well as the discrimination between viable
      and nonviable Legionella. It simultaneously combines the specific detection of
      Legionella cells using antibodies and a bacterial viability marker (ChemChrome
      V6), the enumeration being achieved by epifluorescence microscopy. The
      performance of this immunological double-staining (IDS) method was investigated
      in 38 natural filterable water samples from different aquatic sources, and the
      viable Legionella counts were compared with those obtained by the standard
      culture method. The recovery rate of the IDS method is similar to, or higher
      than, that of the conventional culture method. Under our experimental conditions,
      the limit of detection of the IDS method was <176 Legionella cells per liter. The
      examination of several samples in duplicates for the presence of L. pneumophila
      and other Legionella spp. indicated that the IDS method exhibits an excellent
      intralaboratory reproducibility, better than that of the standard culture method.
      This immunological approach allows rapid measurements in emergency situations,
      such as monitoring the efficacy of disinfection shock treatments. Although its
      field of application is as yet limited to filterable waters, the double-staining
      method may be an interesting alternative (not equivalent) to the conventional
      standard culture methods for enumerating viable Legionella when rapid detection
      is required.

PMID- 16000825
TI  - Multiple-mutation reaction: a method for simultaneous introduction of multiple
      mutations into the glpK gene of Mycoplasma pneumoniae.
AB  - In Mycoplasma pneumoniae, the UGA opal codon specifies tryptophan rather than a
      translation stop site. This often makes it difficult to express Mycoplasma
      proteins in E. coli isolates. In this work, we developed a strategy for the one
      step introduction of several mutations. This method, the multiple-mutation
      reaction, is used to simultaneously replace nine opal codons in the M. pneumoniae
      glpK gene.

PMID- 16000826
TI  - High-level expression and secretion of methyl parathion hydrolase in Bacillus
      subtilis WB800.
AB  - The methyl parathion hydrolase (MPH)-encoding gene mpd was placed under the
      control of the P43 promoter and Bacillus subtilis nprB signal peptide-encoding
      sequence. High-level expression and secretion of mature, authentic, and stable
      MPH were achieved using the protease-deficient strain B. subtilis WB800 as the
      host.

PMID- 16000827
TI  - Epizootiological modeling of Pandora neoaphidis mycosis transmission in Myzus
      persicae colonies initiated by primarily infected alates.
AB  - Pandora neoaphidis transmission was monitored within progeny colonies initiated
      by infected Myzus periscae alates individually flown for 1 to 5 h. Mycosis
      progress in the colonies was well fitted (r2= 0.97) to a modified logistic or
      Gompertz model that included their flight distance, postflight survival time,
      premycosis fecundity, and primary infection rate as influential variables.

PMID- 16000828
TI  - Prevalence and antimicrobial resistance of Campylobacter spp. and Salmonella
      serovars in organic chickens from Maryland retail stores.
AB  - Retail organic (n = 198) and conventional (n = 61) chickens were analyzed. Most
      organic (76%) and conventional (74%) chickens were contaminated with
      campylobacters. Salmonellae were recovered from 61% of organic and 44% of
      conventional chickens. All Salmonella enterica serovar Typhimurium isolates from
      conventional chickens were resistant to five or more antimicrobials, whereas most
      S. enterica serovar Typhimurium isolates (79%) from organic chickens were
      susceptible to 17 antimicrobials tested.

PMID- 16000829
TI  - Genes involved in cyclic lipopeptide production are important for seed and straw
      colonization by Pseudomonas sp. strain DSS73.
AB  - Survival in natural bulk soil and colonization of sugar beet seeds and barley
      straw residues were determined for Pseudomonas sp. strain DSS73 and Tn5 mutants
      in amsY (encoding a peptide synthetase involved in production of the cyclic
      lipopeptide amphisin) and gacS (encoding the sensory kinase of the two-component
      GacA/GacS regulatory system). No differences in survival or growth in response to
      carbon amendment (citrate) were observed in bulk soil. However, both mutants were
      impaired in their colonization of sugar beet seeds and barley straw residues by
      an inoculum established in the bulk soil. The two mutants had comparable
      colonization phenotypes, suggesting that amphisin production is more important
      for colonization than other gacS-controlled traits.

PMID- 16000830
TI  - Assessment of soil microbial community structure by use of taxon-specific
      quantitative PCR assays.
AB  - Here we describe a quantitative PCR-based approach to estimating the relative
      abundances of major taxonomic groups of bacteria and fungi in soil. Primers were
      thoroughly tested for specificity, and the method was applied to three distinct
      soils. The technique provides a rapid and robust index of microbial community
      structure.

PMID- 16000831
TI  - Analysis of microbial gene transcripts in environmental samples.
AB  - We analyzed gene expression in marine and freshwater bacterioplankton communities
      by the direct retrieval and analysis of microbial transcripts. Environmental
      mRNA, obtained from total RNA by subtractive hybridization of rRNA, was reverse
      transcribed, amplified with random primers, and cloned. Approximately 400 clones
      were analyzed, of which approximately 80% were unambiguously mRNA derived. mRNAs
      appeared to be from diverse taxonomic groups, including both Bacteria (mainly
      alpha- and gamma-Proteobacteria) and Archaea (mainly Euryarchaeota). Many
      transcripts could be linked to environmentally important processes such as sulfur
      oxidation (soxA), assimilation of C1 compounds (fdh1B), and acquisition of
      nitrogen via polyamine degradation (aphA). Environmental transcriptomics is a
      means of exploring functional gene expression within natural microbial
      communities without bias toward known sequences, and provides a new approach for
      obtaining community-specific variants of key functional genes.

PMID- 16000833
TI  - Bacterial diversity in rhizospheres of nontransgenic and transgenic corn.
AB  - Bacterial diversity in transgenic and nontransgenic corn rhizospheres was
      determined. In greenhouse and field studies, metabolic profiling and molecular
      analysis of 16S rRNAs differentiated bacterial communities among soil textures
      but not between corn varieties. We conclude that bacteria in corn rhizospheres
      are affected more by soil texture than by cultivation of transgenic varieties.

PMID- 16000832
TI  - 16S rRNA phylogeny of sponge-associated cyanobacteria.
AB  - Phylogenetic analyses of 16S rRNA sequences of sponge-associated cyanobacteria
      showed them to be polyphyletic, implying that they derived from multiple
      independent symbiotic events. Most of the symbiont sequences were affiliated to a
      group of Synechococcus and Prochlorococcus species. However, other symbionts were
      related to different groups, such as the Oscillatoriales.

PMID- 16000834
TI  - Distribution of botulinum toxin-producing clostridia in soils of Argentina.
AB  - We studied the presence of botulinum toxin-producing clostridia in 2,009 soil
      samples from five geographical regions of Argentina. The prevalence was 23.5%,
      and the distribution was not homogeneous among the regions. We observed a great
      multiplicity of serological types and a higher prevalence in nonvirgin soils than
      in virgin soils.

PMID- 16000835
TI  - Impacts of goethite particles on UV disinfection of drinking water.
AB  - A unique association between bacterial cells and small goethite particles
      (approximately 0.2 by 2 microm) protected Escherichia coli and Pseudomonas putida
      from UV inactivation. The protection increased with the particle concentration in
      the turbidity range of 1 to 50 nephelometric turbidity units and with the
      bacterium-particle attachment time prior to UV irradiation. The lower degree of
      bacterial inactivation at longer attachment time was mostly attributed to the
      particle aggregation surrounding bacteria that provided shielding from UV
      radiation.

PMID- 16000836
TI  - Elucidating the key member of a linuron-mineralizing bacterial community by PCR
      and reverse transcription-PCR denaturing gradient gel electrophoresis 16S rRNA
      gene fingerprinting and cultivation.
AB  - A bacterial community from Danish agricultural soil was enriched with linuron [N
      (3,4-dichlorophenyl)-N'-methoxy-N'-methylurea] as the sole carbon and nitrogen
      source. The community mineralized [ring-U-14C]linuron completely to 14CO2 and 14C
      biomass. Denaturing gradient gel electrophoresis analysis and cultivation
      revealed that a Variovorax sp. was responsible for the mineralization activity.

PMID- 16000837
TI  - Identification and functional analysis of Escherichia coli cysteine
      desulfhydrases.
AB  - In Escherichia coli, three additional proteins having L-cysteine desulfhydrase
      activity were identified as O-acetylserine sulfhydrylase-A, O-acetylserine
      sulfhydrylase-B, and MalY protein, in addition to tryptophanase and cystathionine
      beta-lyase, which have been reported previously. The gene disruption for each
      protein was significantly effective for overproduction of L-cysteine and L
      cystine. Growth phenotype and transcriptional analyses suggest that tryptophanase
      contributes primarily to L-cysteine degradation.

PMID- 16000838
TI  - Colonic microbiota signatures across five northern European countries.
AB  - The composition of the colonic microbiota of 91 northern Europeans was
      characterized by fluorescent in situ hybridization using 18 phylogenetic probes.
      On average 75% of the bacteria were identified, and large interindividual
      variations were observed. Clostridium coccoides and Clostridium leptum were the
      dominant groups (28.0% and 25.2%), followed by the Bacteroides (8.5%). According
      to principal component analysis, no significant grouping with respect to
      geographic origin, age, or gender was observed.

PMID- 16000839
TI  - Effect of an artificial RNA marker on gene expression in Escherichia coli.
AB  - Transcriptional analysis was used to examine the effect of a genomically encoded
      artificial RNA on Escherichia coli in rich and minimal media. Only the expression
      of a single gene, deoC, was unequivocally affected under both conditions. E. coli
      marker strains of this type may be useful in monitoring the fate and transport of
      bacteria in various applications.

PMID- 16000841
TI  - Proceedings of the 7th annual meeting of the Japan endocrine pathology society:
      features of malignant endocrine tumors that predict clinical prognosis.

PMID- 16000840
TI  - Prognostic indicators in pituitary tumors.
AB  - Recent advances in molecular pathology have shed light not only on the cellular
      composition and derivation of various tumors, but also on their growth potential,
      likelihood of recurrence, and prognosis. The development of reliable and
      prognostically informative methods of assessing tumor behavior is particularly
      important in pituitary tumors, where no precise correlation exists between
      morphology and clinical aggressiveness. Among the numerous morphologic techniques
      that have been introduced in the last three decades, some have gained popularity
      due to their reliability and ease of performance, whereas others have fallen from
      favor due to their inconsistency and insensitivity in distinguishing indolent
      from aggressive pituitary tumors. Yet others, due to cost and complexity, never
      came into general use. We predict that the immunohistochemical methods now in use
      for assessment of tumor behavior will be complemented and partly replaced by
      molecular genetic procedures in the future.

PMID- 16000842
TI  - Histopathological diagnosis and prognostic factors in adrenocortical carcinoma.
AB  - A great majority of adrenocortical tumors are benign, and many adrenocortical
      carcinomas (ACC) are obviously malignant at presentation. The histopathological
      diagnosis of ACC is occasionally difficult, particularly with stage I and stage
      II disease. The prognosis of ACC is generally poor. Surgery is the major
      treatment, with chemotherapy and radiotherapy being applicable to only restricted
      patients. The Weiss criteria are useful in diagnosing the common adult type of
      ACC. Histopathological prognostic factors of ACC have not been fully established
      because of the rarity of the disease. In this article, we first describe the
      current histopathological diagnostic and prognostic factors of ACC, highlighting
      the special types of ACC to which Weiss's criteria are not fully applicable.
      These special type tumors include pediatric adrenocortical tumors, oncocytomas,
      and aldosterone-producing tumors of pure zona glomerulosa type. Then we present
      three cases with unusual small adrenocortical tumors. One patient had an
      unequivocal ACC showing metastatic disease. One had a histologically defined ACC
      with no metastasis or macroscopic invasion. The third was a pediatric patient
      with a tumor showing a nodule-in-nodule pattern with insulin-like growth factor
      II expression.

PMID- 16000843
TI  - Histological grading of adrenal and extra-adrenal pheochromocytomas and
      relationship to prognosis: a clinicopathological analysis of 116 adrenal
      pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38
      malignant tumors.
AB  - Pheochromocytomas and extra-adrenal sympathetic paragangliomas show varied
      histological patterns, and it is difficult to diagnose malignancy or predict the
      clinical course using current histological criteria. In the present study, we
      reviewed 146 sympathetic paragangliomas including 116 adrenal (102 unilateral, 14
      bilateral) and 30 extra-adrenal tumors including 38 metastatic tumors. We
      developed a scoring scale according to the following six factors: histological
      pattern, cellularity, coagulation necrosis, vascular/capsular invasion, Ki-67
      immunoreactivity, and types of catecholamine produced. The tumors were classified
      as well (WD), moderately (MD), and poorly differentiated (PD) types according to
      their scores. The frequency of these tumor types were 113 WD (77%), 27 MD (19%),
      and 6 PD (4%). Metastasis was observed in 15 of 113 WD (13%), 17 of 27 MD (63%),
      and all 6 PD (100%). Five-year survivals of patients with metastases were 92%
      with WD, 69% with MD, 0% with PD. Respective 10-yr survivals were 83%, 38%, and
      0%. Differences between groups were statistically significant. The data show that
      using this grading scoring system for sympathetic paragangliomas correlates with
      both metastatic potential and patient survival.

PMID- 16000844
TI  - Pathological assessment of pancreatic endocrine tumors for metastatic potential
      and clinical prognosis.
AB  - The prognostic significance of several pathological factors (tumor size, mitotic
      index, Ki-67 labeling index, and vascular invasion) and expression of exocrine
      markers (CA19-9, CEA, AFP, and trypsin) in pancreatic endocrine tumors was
      studied. A total of 20 specimens of metastasizing (n = 10) and non-metastasizing
      (n = 10) tumors were subjected to histological and immunohistochemical
      examination. The metastasizing tumors showed significantly larger size, higher Ki
      67 labeling index, increased number of mitotic cells, and more frequent vascular
      invasion in comparison with the non-metastasizing tumors. It was difficult to
      determine the effect of individual factors on clinical outcome because of slow
      disease progression in almost all cases. Numerous mitotic cells and widespread
      necrosis, however, were thought to indicate a poor prognosis, and tumors with
      these characteristics were regarded as high-grade malignant endocrine carcinomas.
      In one case, one-third of the tumor tissue comprised trypsin-positive cells, the
      outcome was comparatively poor, and the behavior of the tumor resembled that of
      mixed acinar-endocrine carcinoma. A simple multifactorial approach may be
      effective for the identification of tumors at increased risk of metastasis, but
      it remains difficult to determine clinical prognosis. It is essential to at least
      distinguish high-grade endocrine carcinomas from the more common endocrine
      tumors.

PMID- 16000846
TI  - Proposal for the histological classification of parathyroid carcinoma.
AB  - Although the criteria of Schantz and Castleman are widely used in the diagnosis
      of parathyroid carcinoma, many tumors diagnosed as carcinoma subsequently do not
      recur. In addition, although Bondeson's criteria are used to grade parathyroid
      carcinoma, instances of patient mortality have been documented even in cases
      where the histological features did not conform to the criteria for high grade.
      Considering our experience, we believe that the subclassification of parathyroid
      carcinomas defining tumors limited local infiltration as low-grade and those with
      widespread infiltration as high-grade may be useful.

PMID- 16000845
TI  - Significance of an insular component in follicular thyroid carcinoma with distant
      metastasis at initial presentation.
AB  - Risk factors for distant metastasis were studied in 82 patients with follicular
      thyroid carcinoma (FTC). Metastases to either the lung or bone existing at the
      time of presentation were confirmed by I-131 radio-iodine uptake in 10 patients.
      FTC with an insular component was found in eight patients. Univariate analysis of
      14 possible risk factors showed 7 to be statistically significant: insular
      component, poorly differentiated carcinoma, trabecular component, serum
      thyroglobulin level before surgery, patient age at the time of presentation,
      solid component, and vascular invasion (ranked by p values). After further
      analysis of the interrelation of the factors and of the logistic regression
      curves, we concluded that presence of an insular component and patient age were
      the only independent risk factors. Distant metastasis was not detected in any of
      the 27 patients < or = 49 yr old. Among the 55 older patients (> or = 50 yr old),
      5 of the 49 (10%) without an insular component and 5 of the 6 (83%) with an
      insular component had distant metastasis. The remaining older patient with an
      insular component but without distant metastasis showed a gradual increase in
      thyroglobulin levels after total thyroidectomy.

PMID- 16000848
TI  - The role of cytokeratin 19 in the differential diagnosis of true papillary
      carcinoma of thyroid and papillary carcinoma-like changes in Graves' disease.
AB  - Graves' disease is an autoimmune disease predominantly seen in females. All types
      of thyroid cancers may co-exist with Graves' disease but papillary carcinoma is
      the most frequent. Vesicular nuclei, nuclear grooves, and papillary formations
      that may be seen in Graves' disease may lead the pathologist to an overdiagnosis
      of papillary carcinoma. The differential diagnosis between a true papillary
      carcinoma and foci mimicking papillary carcinoma in Graves' disease may be
      challenging by light microscopic features only. This study is designed to
      determine whether CK19 is effective in the discrimination between the true
      papillary carcinoma of thyroid and foci resembling papillary carcinoma in Graves'
      disease. Twenty-five cases with papillary carcinoma and 25 cases with Graves'
      disease containing foci resembling papillary carcinoma were included in the
      study. All 25 cases with papillary carcinoma stained positive with CK19, whereas
      only six of 25 cases with Graves' disease showed weak staining, and the remaining
      19 cases were completely negative. It is known that CK19 may show faint staining
      in benign thyroid lesions such as adenomas. Staining pattern with CK19 together
      with histopathological findings may be helpful in the differential diagnosis
      between foci mimicking papillary carcinoma and true papillary carcinoma in
      Graves' disease.

PMID- 16000847
TI  - Expression of retinoblastoma protein in human growth hormone-secreting pituitary
      adenomas.
AB  - The retinoblastoma gene (RB1) is a tumor-suppressor gene in chromosomal region
      13q14.2. Its role in the pathogenesis of pituitary tumors has not been fully
      clarified. Some studies have shown that losses in this chromosomal region are
      related to aggressive tumor behavior, although the retinoblastoma protein (pRB)
      is still expressed. Conversely, lack of expression of pRB was observed in one
      fourth of GH-secreting pituitary adenomas (GH-tumors). In order to further study
      the expression of pRB in GH-tumors, we evaluated this protein in 49 tumors from
      patients with acromegaly (20 noninvasive, 25 invasive, and 4 with no information)
      and 8 normal pituitaries using immunohistochemistry (IHC). Nuclear staining for
      pRB ranged from 0 to 90% (median 40%) in the tumors and from 40 to 80% (median
      58%) in normal pituitaries. In 10 tumors (20% of total) the adenomatous cells
      were negative (5 cases) or had very low labeling (5 cases) for pRB. Sixty three
      percent (31/49) of the tumors showed staining in 10-80% of the cells and in 16%
      (8/49) of the cases >80% of the adenomatous cells were positive for pRB. The
      expression of pRB was not different in invasive and noninvasive tumors. In
      conclusion, pRB is underexpressed in a subgroup of GH-tumors, and this may
      represent an early event in the pathogenesis of this tumor subtype.

PMID- 16000850
TI  - Pleomorphic leiomyosarcoma of the adrenal gland with osteoclast-like giant cells.
AB  - Pleomorphic leiomyosarcoma (PLMS) of the adrenal gland is a rare tumor in an
      unusual location. A primary PLMS of the left adrenal gland is reported in a 59-yr
      old Mexican woman who presented progressive flank pain and weight loss. The tumor
      measured 16 cm in diameter, showed markedly pleomorphic and osteoclast-like giant
      cells, necrosis, and high mitotic activity (average 15 per 10 high-power fields).
      The phenotype was supported by light microscopy and corroborated by
      immunohistochemistry. The neoplastic cells were strongly positive for muscle
      specific actin, desmin, vimentin, and p53. They were negative for CD34, HMB45,
      estrogen receptors, and S-100 protein. The percentage of Ki-67 positive
      neoplastic cells was 7.6%. DNA content analysis by flow cytometry showed that
      tumor was diploid, with a high level of apoptosis. Extra-adrenal primary sites of
      origin were clinically excluded. The patient developed local recurrence and liver
      metastases 12 mo after initial treatment. She then received adjuvant chemotherapy
      and radiotherapy and the metastasis was resected. Twenty-four months later, she
      is alive with no evidence of disease. This is the second case of adrenal PLMS
      reported. This case exhibited a high histologic grade, aggressive behavior, and
      p53 overexpression, but diploid DNA content.

PMID- 16000849
TI  - Angiopoietins are expressed in the normal rat pituitary gland.
AB  - Interaction of vascular endothelial growth factor (VEGF) with the angiopoietins
      (Ang) is an essential component of angiogenesis. Localization of VEGF in the
      anterior pituitary raises the possibility that Ang must be present in the
      pituitary gland as well. In this study Ang expression was detected in the normal
      rat pituitary gland at the gene level by reverse-transcriptase polymerase chain
      reaction and at the protein level by immunohistochemistry. The latter was
      analyzed by both light and confocal microscopy. Constitutive expression of Ang1,
      Ang2, and their receptor Tie2 was detected at both the mRNA and protein level in
      all the pituitary glands studied. Of interest was the localization of both Ang1
      and Ang2 in scattered PAS positive adenohypophysial cells rather than in
      endothelial cells. Confocal microscopy showed colocalization of both Ang1 and
      Ang2 proteins within the same adenohypophysial cells. Dual immunostaining for
      Ang1 and the anterior pituitary hormones that show PAS positivity demonstrated
      colocalization of Ang1 with follicle stimulating hormone and luteinizing hormone.
      In the posterior pituitary, strong Ang1 signal observed in vascular endothelial
      cells masked the weak Ang2 signal, a pattern that is similar to that reported in
      brain endothelial cells. The presence of both angiopoietins and VEGF in the
      pituitary gland suggest that these ligands interact during angiogenesis as they
      are known to do in other systems to maintain the rich vascular network of the
      gland. This first report of angiopoietin localization in the rat pituitary gland
      opens a new line of investigation on angiogenesis in pituitary glands that will
      impact human endocrinology in the future.

PMID- 16000851
TI  - Warthin tumor-like variant of papillary thyroid carcinoma: a case with
      dedifferentiation (anaplastic changes) and aggressive biological behavior.
AB  - Warthin tumor-like variant of papillary thyroid carcinoma is uncommon and approx
      80 cases have been reported in the literature. This tumor is often associated
      with a favorable prognosis. In this report, a Warthin tumor-like variant of the
      papillary thyroid carcinoma, 5-cm in maximum dimension, underwent anaplastic
      changes in a 74-yr-old woman. The tumor was positive for CD15 and EMA, and a high
      proliferative index was noted in the anaplastic area. The patient developed
      distant metastases after operation and died of the disease 18 mo after the
      operation. The present case is the first reported case of Warthin tumor-like
      variant of papillary thyroid carcinoma with anaplastic changes.

PMID- 16000852
TI  - Interferon research: a brief history.
AB  - Interferons are the antiviral early inflammatory proteins produced in the cells
      in response to the infectious agents. The characterization of the interferon
      genes, their expression, and their function was advanced with the development of
      novel techniques in molecular and cellular biology. Using genetically modified
      mice revealed the critical role of the interferons in innate and acquired immune
      response. The critical steps and discovery that lead to the understanding of the
      interferon system and its role in the antiviral immune response are summarized in
      this chapter.

PMID- 16000853
TI  - Virus infection and the interferon response: a global view through functional
      genomics.
AB  - The primary focus of this chapter is on providing an overview of how we use the
      tools of functional genomics to study virus infection, the interferon response,
      and the mechanisms by which viruses attenuate or evade this response to ensure
      successful replication. We provide examples of the types of analyses we perform,
      experimental design considerations, and the tools and techniques we use for data
      processing and mining. We have not attempted to provide detailed protocols for
      performing microarray or proteomics experiments because even individual
      components of such analyses, for example, techniques for the isolation and
      amplification of ribonucleic acid, could easily be the subject of an entire
      chapter. Rather, our goal is to show how data obtained from global gene
      expression and protein profiling can be used to gain new insights into virus-host
      interactions, with particular emphasis on the interferon response and its
      modulation by virus infection.

PMID- 16000854
TI  - Genomic DNA affinity chromatography: a technique to isolate interferon-inducible
      DNA binding factors.
AB  - Cytokines elicit responses in target cells by inducing changes in gene
      expression. For interferons (IFNs), this involves receptor-mediated activation of
      specific transcription factors, which then translocate into the nucleus to bind
      to cognate gene elements in the promoters of IFN-inducible genes. The prototypic
      IFN-inducible transcription factors are the signal transducer and activator of
      transcription (STAT) proteins. IFN-receptor interactions invoke Janus kinase
      activation via phosphorylation events, which in turn leads to the recruitment and
      phosphorylation of STAT proteins on tyrosine residues. Activated STATs then
      dimerize to form STAT complexes. IFNs-alpha/beta will activate STAT-1, STAT-2,
      STAT-3 ,and STAT-5, whereas IFN-gamma will predominantly activate STAT-1. In this
      chapter, we describe a procedure to identify IFN-inducible deoxyribonucleic acid
      (DNA) binding factors independently of any knowledge of their target DNA
      sequences. This procedure permits the identification of IFN-inducible STAT
      complexes as well as any other IFN-inducible DNA binding factors. This
      biochemical technique uses genomic DNA affinity chromatography to isolate DNA
      binding factors from IFN-inducible cytoplasmic or nuclear extracts.

PMID- 16000855
TI  - Protein engineering of interferon alphas.
AB  - Interferon (IFN)-alphas constitute a family of proteins exhibiting high degree of
      homology in primary, secondary, and tertiary structure and display a high level
      of species specificity in their biological properties. However, small structural
      differences in these proteins may be responsible for a significant variety of
      biological actions. Understanding the structure and function of human IFN-alpha
      is very important. Recombinant techniques are important tools for the production
      and modification of IFN proteins. The first IFN hybrid, IFN-alpha1/alpha2 was
      constructed using recombinant technology in 1981. Subsequently, a number of IFN
      hybrids and mutants have been constructed, expressed and characterized. These
      hybrids and mutants have resulted in novel IFNs that either combine different
      biological properties from the parental proteins or have significantly different
      biological activity. Therefore, IFN hybrids and mutants have provided a powerful
      tool for studying the structure and function of these molecules. Also, these
      engineered IFNs may have important new therapeutic applications and may provide
      greater sights into understanding of the clinical activities of these molecules.

PMID- 16000856
TI  - Assays for the interferon-induced enzyme 2',5' oligoadenylate synthetases.
AB  - Inhibition of protein synthesis by interferon treatment is mediated by two major
      pathways: the 2'-5'-linked oligoadenylates [2-5 (A)] synthetase-RNase L pathway
      and the double-stranded ribonucleic acid-dependent protein kinase-mediated
      pathway. 2-5 (A) synthetases are unique interferon-inducible enzymes that, upon
      activation by double-stranded RNA, polymerize adenosine triphosphate (ATP) to 2-5
      (A) synthases. These 2-5 (A) synthetases bind and activate the latent RNase L,
      causing RNA degradation. In addition to the three major size classes of
      enzymatically active oligoadenylate synthetase proteins, at least one inactive
      oligoadenylate synthetase is known in human and mouse. Structure-function studies
      and recent crystal structure determination have identified several distinct sites
      in these proteins responsible for different biochemical functions. RNase L is the
      only known protein that binds to 2-5 (A) synthetases with very high affinity.
      Gene knockout studies of RNase L have identified its role in antiviral actions of
      interferon and in apoptosis. Recently, it has also been implicated in prostate
      cancer metastasis. In this chapter we describe several methodologies for studying
      biochemical and physiological properties of the 2-5 (A) synthetase-RNase L
      pathway.

PMID- 16000857
TI  - A convenient and sensitive fluorescence resonance energy transfer assay for RNase
      L and 2',5' oligoadenylates.
AB  - Interferon action against viruses is mediated in part through a ribonucleic acid
      (RNA) decay pathway known as the 2-5A system. Unusual 5'-triphosphorylated, 2',5'
      linked oligoadenylates (2-5A) are produced in mammalian cells by interferon
      inducible 2-5A synthetases (OAS) in response to viral double-stranded RNA. 2-5A
      activates a uniquely regulated endoribonuclease, RNase L, resulting in the
      cleavage of single-stranded viral and cellular RNAs, thus suppressing viral
      replication. In addition, RNase L was recently identified as a strong candidate
      for the hereditary prostate cancer 1 susceptibility allele. RNase L is
      ubiquitously expressed at basal levels in a wide range of mammalian cell types.
      Conventional RNase L assays, which can be inconvenient and cumbersome, typically
      involve cleavage of radioactively labeled RNA species or of endogenous ribosomal
      RNA. Here we describe a convenient, rapid, nonradioactive, and relatively
      inexpensive fluorescence resonance energy transfer (FRET) that may be used to
      accurately measure levels of either 2-5A or RNase L activity with a high degree
      of specificity and sensitivity. The RNA probe used in the FRET assay was designed
      based on a region of respiratory syncytial genomic RNA. We demonstrate the
      utility of our FRET assay with several novel biostable analogs of 2-5A.

PMID- 16000858
TI  - Regulation of murine interferon regulatory factor gene expression in the central
      nervous system determined by multiprobe RNase protection assay.
AB  - Despite a key role in the regulation of interferon (IFN) gene expression and in
      mediating many downstream actions of the IFNs, the regulation of IFN regulatory
      factor (IRF) gene expression in the normal and pathological central nervous
      system and, indeed, other tissues, is poorly defined. We sought to examine the
      expression and regulation of the IRF genes in a number of different murine models
      for immune- or virally induced central nervous system disease. Here, we describe
      the development of a multiprobe RNase protection assay that permits the
      simultaneous detection and quantification of IRF ribonucleic acid transcripts for
      multiple family members in murine cells and tissues.

PMID- 16000859
TI  - Mitogen-activated protein kinase pathways in interferon signaling.
AB  - There is recent evidence that in addition to the classic JAK/STAT pathways,
      mitogen-activated proteins (MAP) kinase pathways play important roles in Type I
      interferon signaling and the generation of interferon responses. In particular,
      the p38 MAP kinase cascade exerts positive regulatory roles on transciptional
      activation of interferon-sensitive genes (ISGs) and the induction of the
      antiproliferative and antiviral properties of interferons. In this chapter,
      methodologies to detect activation of p38 and various upstream and downstream
      effectors are provided. Also, the methodological approaches used to examine the
      role of this pathway on the regulation of hematopoiesis are discussed.

PMID- 16000860
TI  - Development of an interferon-based cancer vaccine protocol: application to
      several types of murine cancers.
AB  - A protocol for the development of cancer vaccines is presented. The protocol is
      based upon the long-term in vitro treatment of cancer cells with interferon (IFN)
      alpha to create cancer vaccine cells. This protocol has been used to develop
      cancer vaccines in mice against B16 melanoma, RM-1 prostate cancer, and P388
      lymphocytic leukemia. A detailed description of the protocol is presented.
      Important considerations that are discussed include the method of selection of
      potential cancer vaccine cells that would make good models for cancer vaccines
      for human cancers, the effects of in vitro IFN-alpha treatment concentration on
      the efficacy of generated cancer vaccine cells, the differential ability of
      cancer cells to become efficacious cancer vaccine cells in response to IFN-alpha
      treatment, the determination of the effectiveness of ultraviolet-light killing of
      various cancer cell types for generating cancer vaccine cells, and the methods of
      evaluation of statistical significance of the data obtained. Potential problems
      also are addressed.

PMID- 16000861
TI  - Type I interferons as regulators of the differentiation/activation of human
      dendritic cells: methods for the evaluation of IFN-induced effects.
AB  - Recent studies have revealed that type I interferons (IFNs) are powerful inducers
      of the differentiation and activation of dendritic cells (DCs). These findings
      emphasize the importance of these cytokines in linking innate and adaptive
      immunity, suggesting that effects of type I IFN on DCs can play a role in the
      antitumor and antiviral activity observed in some IFN-treated patients. Thus, the
      evaluation of the effects of IFN on the differentiation/activation of DCs has
      become an important approach for testing novel biologically important IFN
      activities, and the description of some reference methods are urgently needed. In
      this chapter, we describe some methods for testing the effects of IFNs on the
      differentiation and activation of human DCs from the peripheral blood monocytes
      and for the characterization of the DCs generated after IFN treatment.

PMID- 16000862
TI  - Flow cytometric techniques for studying plasmacytoid dendritic cells in mixed
      populations.
AB  - Plasmacytoid dendritic cells (PDCs) are the natural interferon (IFN-alpha)
      producing cells in human peripheral blood that produce vast quantities of IFN
      alpha in response to viral infection and other stimuli. PDCs are a rare cell
      type, making up less than 0.5% of peripheral blood mononuclear cells. To date,
      these cells have not been successfully cultured in vitro and are very sensitive
      to selection via magnetic bead labeling, making them very difficult to study as a
      purified population. Therefore, our laboratory has developed techniques to study
      PDCs in mixed populations. Using flow cytometry to label specific cell-surface
      markers, PDCs can be easily identified from other peripheral blood mononuclear
      cells or in mononuclear cell suspensions of lymphoid tissue. PDCs can also be
      permeabilized and stained for intracellular proteins or cytokines. Using surface
      and intracellular flow cytometry, phenotypic and functional aspects can be
      combined to accurately study PDCs in a mixed population of cells.

PMID- 16000863
TI  - Analysis of anti-interferon properties of the herpes simplex virus type I ICP0
      protein.
AB  - A defining hallmark of the type 1 interferons (IFNs) is their ability to
      interfere with virus replication. As such, viruses have evolved diverse
      mechanisms to subvert the antiviral effects of interferons. Herpes simplex virus
      type 1 (HSV-1) is a large deoxyribonucleic acid virus best known for its ability
      to cause cold sores in infected individuals. In cultured cells, HSV-1 is
      relatively resistant to the effects of IFNs. Plaque reduction assays were used to
      determine that the immediate early HSV-1 gene product ICP0 functions in part to
      ensure successful replication in the presence of an IFN-induced antiviral
      response. Northern blot analysis showed that in the absence of ICP0, HSV-1
      transcript accumulation is significantly decreased. Finally, nuclear run-on
      assays demonstrated that ICP0 functions to overcome IFN-induced blocks to virus
      transcription. The methods used in these studies are described in detail in this
      section.

PMID- 16000864
TI  - Interferon subtype gene therapy for regulating cytomegalovirus disease.
AB  - Delivery of type I interferon (IFN) subtypes by intramuscular inoculation of mice
      with a recombinant mammalian expression vector encoding IFN stimulates the immune
      response. Such immunomodulation drives towards a Th1-like response. The degree of
      stimulation of the immune response was influenced by several parameters of the
      naked deoxyribonucleic acid (DNA) vaccination protocol. Pretreatment of mice with
      bupivacaine increased transgene expression in situ. The specific subtype gene of
      type I IFN, the DNA concentration, the combined use of two or more subtypes, and
      the timing of the DNA immunisations were all found to influence the level of
      efficacy of IFN gene therapy in a mouse model for cytomegalovirus (CMV) infection
      and disease. In addition, adjuvant therapy, using type I IFN genes, for DNA virus
      vaccination (CMV glycoprotein B) enhanced viral-specific immunity and reduced the
      severity of myocarditis in mice. Thus, type I IFN gene therapy has potent
      adjuvant properties when delivered as DNA and can be used to regulate virus
      infection and disease via pleiotropic actions in the stimulation of immune
      responses.

PMID- 16000865
TI  - Transfection of Mulller cells with type I interferon transgenes: resistance to
      HSV-1 infection.
AB  - Gene transfer is a widely used experimental approach to determine the value of
      specific genes under a variety of conditions. This chapter focuses on the
      expression of two human anti-viral genes, interferon (IFN)-alpha2 and IFN-beta,
      driven by a cytomegalovirus immediate-early promoter in a human Muller cell line.
      The anti-viral efficacy of these two transgenes is determined by measuring
      resistant to herpes simplex virus type 1 infection assessing viral antigen
      expression and viral titers recovered from control and IFN transgene-transfected
      cells. Furthermore, comparing the antiviral efficacy of these two transgenes
      suggest the anti-viral environment elicited by the human IFN-alpha2 transgene is
      superior to that of the human IFN-beta, which may be related to the amount of
      biologically active IFN secreted by these cells.

PMID- 16000866
TI  - The in vitro developmental competence of oocytes from juvenile calves is related
      to follicular diameter.
AB  - This study investigated the relationship between follicle size (FS) and
      developmental competence of calf oocytes. Cumulus-oocyte-complexes (COCs) from
      follicles>8 (L-COCs; n=19), 4-8 (M-COCs; n=54), and 2-3 mm (S-COCs; n=155) were
      recovered from non-stimulated 1-4 months old dairy calves post mortem and ex vivo
      (laparoscopy), and in parallel from slaughtered adult cows from follicles of
      identical size categories [>8 (n=91); 4-8 (n=138); 2-3 mm (n=193)].
      Morphologically intact COCs were subjected to in vitro maturation, fertilization,
      and embryo culture. Cleavage rate (CR; 46 h post-insemination=p.i.), rate of
      morulae/blastocysts (M/Bl; day 7 p.i.), and blastocysts (Bl; day 9 p.i.) were
      recorded. FS had no effect on the CR in calves. However, calf L-COCs yielded the
      highest rates of M/Bl and Bl compared with the two other size categories
      (P<0.05). In contrast, calf S- and M-COCs gave similar rates of M/Bl, whereas the
      proportion of Bl was lowest for S-COCs (P<0.05). This was almost identical to
      findings in cows, except that the CR was highest for L-COCs and M/Bl yields were
      lowest for S-COCs (P<0.05). There were no differences between calf and cows with
      regard to CR for the respective FS categories. L-COCs from calves and cows
      yielded similar rates of M/Bl and Bl, whereas calf S- and M-COCs yielded lower
      rates of Bl than S- and M-COCs from cows and a lower rate of M/Bl when S-and M
      COCs were analyzed as one group (P<0.05). Whereas the CR was similar in calves
      and cows, calf COCs yielded lower rates of M/Bl and Bl (P<0.05). In conclusion,
      the results show that the developmental competence of calf oocytes is higher in
      those derived from follicles larger than 8 mm, and thus are almost equally as
      competent as cow oocytes derived from follicles of identical size. This suggests
      that calf oocytes acquire developmental competence within the large follicle,
      potentially due to a process similar to prematuration of the oocyte in the adult
      cow. It is proposed that procedures that facilitate prematuration, such as
      "coasting" following a preceding superstimulation, might increase the
      developmental competence of calf oocytes.

PMID- 16000868
TI  - Increased lysine N-methylation of a 23-kDa protein during hepatic regeneration.
AB  - The methylation of a 23-kDa nuclear protein increased after partial hepatectomy
      and methylation returned to basal levels after the initial stage of regeneration.
      The methylating enzyme was partially purified from rat liver by ammonium sulfate
      precipitation, DEAE-anion exchange chromatography and Butyl-Sepharose
      chromatography. The 23-kDa protein was purified from a nuclear fraction of liver
      tissue with SP-Sepharose. When the 23-kDa protein was methylated with the
      partially purified methyltransferase and analyzed on C(18) high performance
      liquid chromatography (HPLC), the methylated acceptor amino acid was monomethyl
      lysine (MML). Previously, only arginine N-methylation of specific substrate
      proteins has been reported during liver regeneration. However, in this report, we
      found that lysine N-methylation increased during early hepatic regeneration,
      suggesting that lysine N-methylation of the 23-kDa nuclear protein may play a
      functional role in hepatic regeneration. The methyltransferase did not methylate
      other proteins such as histones, hnRNPA1, or cytochrome C, suggesting the enzyme
      is a 23-kDa nuclear protein- specific lysine N-methyltransferase.

PMID- 16000867
TI  - Genotype-phenotype correlation of SMN locus genes in spinal muscular atrophy
      patients from India.
AB  - Spinal muscular atrophy has been classified into four groups based on the age of
      onset and clinical severity of the disease. Homozygous deletion in SMN1 gene
      causes the disease but the clinical severity may be modified by copy number of
      homologous gene SMN2 as well as the extent of deletion at SMN locus. In the view
      of scarcity of genotype and phenotype correlation data from India, this study has
      been undertaken to determine that correlation in SMA patients by using the SMN
      and NAIP genes and two polymorphic markers C212 and C272 located in this region.
      Two to four alleles of the markers C212 and C272 were observed in normal
      individuals. However, majority of Type I patients showed only one allele from
      both markers whereas in Type II and III patients, 2-3 alleles were observed. The
      SMN2 copy number in our type III patients showed that patients carry 3-5 copies
      of SMN2 gene. Our results suggest that extent of deletions encompassing H4F5,
      SMN1, NAIP and copy number of SMN2 gene can modify the SMA phenotype, thus
      accounting for the different clinical subtypes of the disease.

PMID- 16000869
TI  - Inositol 5'-phosphatase, SHIP1 interacts with phospholipase C-gamma1 and
      modulates EGF-induced PLC activity.
AB  - Phospholipase C-gamma1, containing two SH2 and one SH3 domains which participate
      in the interaction between signaling molecules, plays a significant role in the
      growth factor-induced signal transduction. However, the role of the SH domains in
      the growth factor-induced PLC-gamma1 regulation is unclear. By peptide-mass
      fingerprinting analysis, we have identified SHIP1 as the binding protein for the
      SH3 domain of PLC-gamma1. SHIP1 was co-immunoprecipitated with PLC-gamma1 and
      potentiated EGF-induced PLC-gamma1 activation. However, inositol 5'-phosphatase
      activity of SHIP1 was not required for the potentiation of EGF-induced PLC-gamma1
      activation. Taken together, these results suggest that SHIP1 may function as an
      adaptor protein which can potentiate EGF-induced PLC-gamma1 activation without
      regards to its inositol 5'-phosphatase activity.

PMID- 16000870
TI  - Modulation of the caveolin-3 and Akt status in caveolae by insulin resistance in
      H9c2 cardiomyoblasts.
AB  - We investigated glucose uptake and the translocation of Akt and caveolin-3 in
      response to insulin in H9c2 cardiomyoblasts exposed to an experimental insulin
      resistance condition of 100 nM insulin in a 25 mM glucose containing media for 24
      h. The cells under the insulin resistance condition exhibited a decrease in
      insulin-stimulated 2-deoxy[(3)H]glucose uptake as compared to control cells grown
      in 5 mM glucose media. In addition to a reduction in insulin-induced Akt
      translocation to membranes, we observed a significant decrease in insulin
      stimulated membrane association of phosphorylated Akt with a consequent increase
      of the cytosolic pool. Actin remodeling in response to insulin was also greatly
      retarded in the cells. When translocation of Akt and caveolin-3 to caveolae was
      examined, the insulin resistance condition attenuated localization of Akt and
      caveolin-3 to caveolae from cytosol. As a result, insulin-stimulated Akt
      activation in caveolae was significantly decreased. Taken together, our data
      indicate that the decrease of glucose uptake into the cells is related to their
      reduced levels of caveolin-3, Akt and phosphorylated Akt in caveolae. We conclude
      that the insulin resistance condition induced the retardation of their
      translocation to caveolae and in turn caused an attenuation in insulin signaling,
      namely activation of Akt in caveolae for glucose uptake into H9c2
      cardiomyoblasts.

PMID- 16000871
TI  - 15-Deoxy-delta12,14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in
      lymphocytes.
AB  - 15-deoxy-delta(12,14)-PGJ(2)(15d-PGJ(2)) is a natural ligand that activates the
      peroxisome proliferators-activated receptor (PPAR) gamma, a member of nuclear
      receptor family implicated in regulation of lipid metabolism and adipocyte
      differentiation. Recent studies have shown that 15d-PGJ(2) is the potent anti
      inflammatory agent functioning via PPARgamma-dependent and -independent
      mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARgamma
      agonists are involved in inhibiting NF-kappaB signaling pathway. We examined the
      possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d
      PGJ(2) in lymphocytes and also examined whether the inhibition of IL-6 signaling
      is dependent of PPARgamma. 15d-PGJ(2) blocked IL-6 induced Stat1 and Stat3
      activation in primary human lymphocytes, Jurkat cells and immortalized rheumatoid
      arthritis B cells. Inhibition of IL-6 signaling was induced rapidly within 15 min
      after treatment of 15d-PGJ(2). Other PPARgamma-agonists, such as troglitazone and
      ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ(2) affect
      the IL-6-induced Jak-Stat signaling pathway via PPARgamma-independent mechanism.
      Although cycloheximide reversed 15d-PGJ(2)-mediated inhibition of Stat3
      activation, actinomycin D had no effect on 15d-PGJ(2)-mediated inhibition of IL-6
      signaling, indicating that inhibition of IL-6 signaling occur independent of de
      novo gene expression. These results show that 15d-PGJ(2) specifically inhibit Jak
      Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ(2) may regulate
      inflammatory reactions through the modulation of different signaling pathway
      other than NF-kappaB in lymphocytes.

PMID- 16000872
TI  - Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes
      (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential
      upstream targets.
AB  - Ultraviolet B (UVB) irradiation of skin induces an acute inflammation.
      Cyclooxygenase-2 (COX-2) protein plays key roles in acute inflammation in UVB
      irradiated keratinocyte cell line HaCaT. Recently, curcumin has been regarded as
      a promising anti-inflammatory agent due to its ability to inhibit COX-2
      expression. However, it remains largely unknown whether curcumin inhibits the UVB
      induced COX-2 expression in HaCaT cells. This study was undertaken to clarify the
      effect of curcumin on the expression of COX-2 in UVB- irradiated HaCaT cells and
      further determined the molecular mechanisms associated with this process. In this
      study, we have found that the expression of COX-2 mRNA and protein were up
      regulated in UVB-irradiated HaCaT cells in a dose- and time-dependent manner.
      Interestingly, treatment with curcumin strongly inhibited COX-2 mRNA and protein
      expressions in UVB-irradiated HaCaT cells. Notably, there was effective
      inhibition by curcumin on UVB-induced activations of p38 MAPK and JNK in HaCaT
      cells. The DNA binding activity of AP-1 transcription factor was also markedly
      decreased with curcumin treatment in UVB-irradiated HaCaT cells. These results
      collectively suggest that curcumin may inhibit COX- 2 expression by suppressing
      p38 MAPK and JNK activities in UVB-irradiated HaCaT cells. We propose that
      curcumin may be applied as an effective and novel sunscreen drug for the
      protection of photoinflammation.

PMID- 16000873
TI  - In vivo ligation of glucocorticoid-induced TNF receptor enhances the T-cell
      immunity to herpes simplex virus type 1.
AB  - GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the
      TNF receptor superfamily. The receptor is preferentially expressed on
      CD4(+)CD25(+) regulatory T cells and GITR signals break the suppressive activity
      of the subset. In this study, we wanted to reveal the in vivo function of GITR in
      herpes simplex virus type 1 (HSV-1) infection. A single injection of anti-GITR
      mAb (DTA-1) immediately after viral infection significantly increased the number
      of CD4(+) and CD8(+) T cells expressing CD25, an activation surface marker, and
      secreting IFN-gamma. We confirmed these in vivo observations by showing ex vivo
      that re-stimulation of CD4(+) or CD8(+) T cells with a CD4(+) or CD8(+) T-cell
      specific HSV-1 peptide, respectively, induced a significant elevation in cell
      proliferation and in IFN-gamma secretion. Our results indicate that GITR signals
      play a critical role in the T-cell immunity to HSV-1.

PMID- 16000874
TI  - COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder
      cancer cells.
AB  - Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor
      development and progression as well as to protect cells from apoptosis induced by
      various cellular stresses. Through a tetracycline-regulated COX-2 overexpression
      system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a
      human bladder cancer cell line, EJ. We also found that the inhibition of anoikis
      by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by
      suppression of the COX-2 effect on anoikis by a PI-3K inhibitor, LY294002.
      Furthermore, COX-2 enhanced Mcl-1 expression in the anoikis process, implying
      that Mcl-1 also may be involved in mediating the survival function of COX-2.
      Together, these results suggest that COX-2 inhibits anoikis by activation of the
      PI-3K/Akt pathway and probably by enhancement of Mcl-1 expression in human
      bladder cancer cells. This anti- anoikis effect of COX-2 may be a part of
      mechanisms to promote tumor development and progression.

PMID- 16000875
TI  - Co-localization and interaction of organic anion transporter 1 with caveolin-2 in
      rat kidney.
AB  - The organic anion transporters (OAT) have recently been identified. Although the
      some transport properties of OATs in the kidney have been verified, the
      regulatory mechanisms for OAT's functions are still not fully understood. The rat
      OAT1 (rOAT1) transports a number of negatively charged organic compounds between
      the cells and their extracellular milieu. Caveolin (Cav) also plays a role in
      membrane transport. Therefore, we investigated the protein-protein interactions
      between rOAT1 and caveolin-2. In the rat kidney, the expressions of rOAT1 mRNA
      and protein were observed in both the cortex and the outer medulla. With respect
      to Cav-2, the expressions of mRNA and protein were observed in all portions of
      the kidney (cortex < outer medulla = inner medulla). The results of Western blot
      analysis using the isolated caveolae-enriched membrane fractions or the
      immunoprecipitates by respective antibodies from the rat kidney showed that rOAT1
      and Cav-2 co-localized in the same fractions and they formed complexes each
      other. These results were confirmed by performing confocal microscopy with
      immunocytochemistry using the primary cultured renal proximal tubular cells. When
      the synthesized cRNA of rOAT1 along with the antisense oligodeoxynucleotides of
      Xenopus Cav-2 were co-injected into Xenopus oocytes, the [(14)C]p-aminohippurate
      and [(3)H]methotrexate uptake was slightly, but significantly decreased. The
      similar results were also observed in rOAT1 over-expressed Chinese hamster ovary
      cells. These findings suggest that rOAT1 and caveolin-2 are co-expressed in the
      plasma membrane and rOAT1's function for organic compound transport is
      upregulated by Cav-2 in the normal physiological condition.

PMID- 16000876
TI  - Presence of autocrine hepatocyte growth factor-Met signaling and its role in
      proliferation and migration of SNU-484 gastric cancer cell line.
AB  - Autocrine stimulation via coexpression of hepatocyte growth factor (HGF) and its
      receptor (Met) has been reported in many human sarcomas, but few in carcinomas.
      In this report, we found that one gastric cancer cell line, SNU-484, among 11
      gastric cell lines tested has an autocrine HGF- Met stimulation. RT-PCR, ELISA
      and scattering assay using MDCK cells revealed that SNU-484 cells secreted a
      significant amount of active HGF (about 1.25 +/- 0.41 ng/24 h/10(6) cells) into
      conditioned medium. Resultantly, Met in this cell line was constitutively
      phosphorylated. Neutralizing antibodies against HGF reduced the tyrosine
      phosphorylation of Met, resulting in the inhibition of cell proliferation and
      migration (P <0.005). To the best of our knowledge, this is the first report on
      autocrine HGF-Met signaling in a gastric cancer cell line. Our observations with
      SNU-484 cells suggest that HGF is involved in the development and/or progression
      of some gastric carcinoma through an autocrine mechanism.

PMID- 16000877
TI  - O-GlcNAc modification on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation
      and induces insulin resistance in rat primary adipocytes.
AB  - It has been known that O-linked beta-N-acetylglucosamine (O-GlcNAc) modification
      of proteins plays an important role in transcription, translation, nuclear
      transport and signal transduction. The increased flux of glucose through the
      hexosamine biosynthetic pathway (HBP) and increased O-GlcNAc modification of
      protein have been suggested as one of the causes in the development of insulin
      resistance. However, it is not clear at the molecular level, how O-GlcNAc protein
      modification results in substantial impairment of insulin signaling. To clarify
      the association of O-GlcNAc protein modification and insulin resistance in rat
      primary adipocytes, we treated the adipocytes with O-(2-acetamido-2deoxy-D
      glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), a potent inhibitor of O
      GlcNAcase that catalyzes removal of O-GlcNAc from proteins. Prolonged treatment
      of PUGNAc (100 microM for 12 h) increased O-GlcNAc modification on proteins in
      adipocytes. PUGNAc also drastically decreased insulin-stimulated 2-deoxyglucose
      (2DG) uptake and GLUT4 translocation in adipocytes, indicating that PUGNAc
      developed impaired glucose utilization and insulin resistance in adipocytes.
      Interestingly, the O-GlcNAc modification of IRS-1 and Akt2 was increased by
      PUGNAc, accompanied by a partial reduction of insulin-stimulated phosphorylations
      of IRS-1 and Akt2. The PUGNAc treatment has no effect on the expression level of
      GLUT4, whereas O-GlcNAc modification of GLUT4 was increased. These results
      suggest that the increase of O-GlcNAc modification on insulin signal pathway
      intermediates, such as IRS-1 and Akt2, reduces the insulin-stimulated
      phosphorylation of IRS-1 and Akt2, subsequently leading to insulin resistance in
      rat primary adipocytes.

PMID- 16000878
TI  - Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun
      pathways in human melanoma cells.
AB  - Expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), which
      correlates with tumor invasion and metastasis, has been known to be regulated by
      several intracellular signaling pathways. Since the CD9 membrane protein has been
      implicated in signal transduction and malignant progression of cancer cells, we
      examined the functional involvement of CD9 in the regulation of MMP-2 and MMP-9
      expression by using stable CD9 transfectant clones of MelJuso human melanoma
      cells. The CD9 cDNA-transfected cells with elevated CD9 expression displayed
      increased MMP-2 and decreased MMP-9 expression when compared with the mock
      transfectant cells. Among several signal pathway inhibitors tested, SB203580 and
      SP600125, which inhibit p38 MAPK and JNK respectively, completely blocked the CD9
      stimulated MMP-2 expression. Phosphorylation levels of p38 MAPK and c-Jun in
      MelJuso cells were also significantly increased by CD9 transfection. In addition,
      the down-regulation of p38 MAPK and JNK by siRNA transfection resulted in a
      decrease in MMP-2 expression by MelJuso cells. Promoter analysis and gel shift
      assay showed that the CD9-induced MMP-2 expression is mediated by a functional AP
      1 site through interactions with AP-1 transcription factors including c-Jun.
      These results suggest that CD9 induces MMP-2 expression by activating c- Jun
      through p38 MAPK and JNK signaling pathways in human melanoma cells.

PMID- 16000879
TI  - Antitumor immunity induced by tumor cells engineered to express a membrane-bound
      form of IL-2.
AB  - Transduction of cytokine gene into tumor cells is a promising method of tumor
      therapy, but the value is limited by accompanying side effects. To focus
      antitumor immune response to tumor antigen-specific CTL, we developed an
      antitumor vaccine by transfecting modified IL-2 gene in a membrane-bound form
      (mbIL-2) into B16F10 melanoma cells. The mbIL-2 clone showed reduced
      tumorigenicity and metastatic ability, and inhibited metastasis and prolonged the
      survival of mice against B16F10 cells. The inhibition of B16F10 metastasis by
      mbIL-2 was accompanied by the increment of CD8(+) T cells. The metastasis of mbIL
      2 clone was significantly increased in the CD8(+) T cell-depleted mice, but not
      in CD4(+) T cell depleted mice. Spleen cells immunized with the mbIL-2 clone
      showed higher CTL activity towards B16F10 cells than those immunized with control
      cells. The size of CD8(+) T cell population in the lung of mice injected with the
      mbIL-2 clone was markedly greater than that of mice injected with B16F10 cells,
      but there was no detectible change in CD4(+) and CD8(+) T cell populations of
      lymph nodes and spleen. These results suggest that when the mbIL-2 clone is
      introduced into the blood stream, it migrates mainly to lung and activates CD8(+)
      T cells in situ, possibly by direct priming. Such a tumor vaccine may ameliorate
      the toxic side effects encountered with conventional cytokine gene therapy.

PMID- 16000880
TI  - Identification of a putative transactivation domain in human Nanog.
AB  - Nanog is a newly identified divergent homeodomain protein that directs the
      infinite propagation and sustains the pluripotency of embryonic stem cells. It
      has been reported that murine Nanog has two potent transactivation domains in N
      terminal and C-terminal regions. Human Nanog (hNanog) polypeptide shares about
      58% and 87% identity to the open reading frame and homeodomain of murine Nanog,
      respectively. However, the functional domains and molecular mechanisms of hNanog
      are poorly understood. In this study, for the first time, we presented that only
      C-terminus of hNanog contains a potent transactivation domain. Based on the amino
      acid sequences of homeobox domain, we roughly divided hNanog open reading frame
      into the three regions such as N-terminal, homeodomain and C-terminal regions and
      constructed either the fusion proteins between hNanog individual and Gal4 DNA
      binding domain or the context of native hNanog protein. Reporter assays by using
      reporter plamid containing Gal4 or Nanog binding site revealed that the only C
      terminal region exhibited the significant fold induction of transactivation.
      However, interestingly, there was no significant activation through N-terminal
      region unlike murine Nanog, suggesting that C-terminal region may have more
      critical roles in the transcriptional activation of target genes. Taken together,
      the finding of a putative transactivation domain in hNanog may contribute to the
      further understanding of molecular mechanism on the regulation of downstream
      genes involved in self-renewal and pluripotency of human stem cells.

PMID- 16000881
TI  - Sec13 induces genomic instability in U2OS cells.
AB  - Sec13p has been known as an endoplasmic reticulum-Golgi transport protein.
      Recently, it has also been shown to be required for the formation of septation in
      the fission yeast Schizosaccharomyces pombe. In the present study, we focused on
      the role of a human homolog of Saccharomyces cerevisiae SEC13, Sec13 protein
      during mitosis in U2OS cells. We found that the expression of Sec13 was constant
      throughout the cell cycle, and localized to the kinetochores at metaphase during
      mitosis. By using green fluorescent protein technology, we observed that Sec13 is
      required for evasion of mitotic arrest in response to spindle damage, leading to
      G1-like phase and apoptotic cell death. In addition, cells expressing exogenous
      Sec13 showed giant nuclei compared to endogenous ones in the absence of
      nocodazole. These results demonstrate that Sec13 is involved in the regulation of
      the metaphase/anaphase transition and may be functionally associated with mitotic
      machinery to maintain genomic stability during mitosis.

PMID- 16000882
TI  - Increased prevalence of varicocele in patients with coronary artery ectasia.
AB  - BACKGROUND: Coronary artery ectasia (CAE) is defined as localized or diffuse non
      obstructive lesions of the epicardial coronary arteries with a luminal dilation
      exceeding the 1.5-fold of normal adjacent segment or vessel diameter. Varicocele
      is the dilatation of the pampiniform plexus. Recently increased prevalence of
      peripheral varicose veins has been shown in patients with CAE. In this study we
      aimed to assess the prevalence of varicocele, which is dilatation of another
      venous system, in patients with CAE. MATERIALS AND METHODS: Thirty-five male
      consecutive patients with coronary artery ectasia in combination with or without
      coronary artery disease (CAD) and 63 male, age-matched patients with coronary
      artery disease were included in the study. All patients were evaluated for the
      presence of varicocele. RESULTS: Twenty-one patients with CAE were found to have
      varicocele (62% of group I patients). In patients with CAD, 24 patients (38%)
      were found to have varicocele. The difference between the two groups in respect
      to presence of varicocele was statistically significant (P=0.02; odds ratio=1.57;
      95% confidence interval 1.05- 2.3). CONCLUSION: We have shown that patients with
      coronary artery ectasia have an increased prevalence of varicocele compared to
      those with coronary artery disease. The mechanism underlying coronary artery
      ectasia might further increase the prevalence of varicocele in susceptible
      patients.

PMID- 16000883
TI  - Patterns of coronary compromise leading to bradyarrhythmias and hypotension in
      inferior myocardial infarction.
AB  - BACKGROUND: Occlusion and reperfusion of the acutely occluded right coronary
      artery may result in abrupt bradycardia and hypotension, attributed to Bezold
      Jarisch cardio-inhibitory reflexes arising from the ischemic left ventricle.
      Given that right ventricular infarction, a result of proximal right coronary
      artery occlusion, predisposes to bradycardia and hypotension, we hypothesized
      that proximal right coronary occlusions would be more likely to result in
      bradycardia-hypotension compared to more distal occlusions. METHODS: In 216
      patients with acute inferior myocardial infarction undergoing primary angioplasty
      of the right coronary artery, we retrospectively analyzed the incidence of
      bradyarrhythmias and hypotension during occlusion and with reperfusion. RESULTS:
      Occlusion proximal to the right ventricular branches was identified in 151 (70%)
      of cases, with occlusions distal but compromising the left ventricular and
      atrioventricular nodal branches in 65 (30%) others. During occlusion, those with
      proximal occlusions were more likely to suffer hypotension (41 versus 15%,
      P=0.0002), advanced atrioventricular block (21 versus 3%, P=0.0008) and
      hypotension with bradycardia (25 versus 9%, P=0.01). Similarly, reperfusion of
      proximal occlusions more frequently resulted in abrupt hypotension (42 versus
      19%, P=0.002), bradycardia (34 versus 14%, P=0.004) and hypotension with
      bradycardia (27 versus 12%, P=0.02). CONCLUSIONS: These data demonstrate that
      during right coronary artery occlusion and with reperfusion, bradycardia and
      hypotension develop more commonly in patients with proximal occlusions compared
      with those with distal occlusions. These findings suggest that reflexes arising
      from the ischemic right ventricle may play a role in bradyarrhythmias and
      hypotension.

PMID- 16000884
TI  - Left ventricular mural thrombus after anterior ST-segment-elevation acute
      myocardial infarction in the era of aggressive reperfusion therapy--still a
      frequent complication.
AB  - BACKGROUND: Left ventricular mural thrombus (LVMT) is a well-known complication
      of anterior ST-elevation acute myocardial infraction (AMI). It remains unknown
      how modern therapies have impacted on its occurrence. OBJECTIVES: To define the
      frequency of LVMT among contemporary patients with anterior ST-elevation AMI, the
      clinical and echocardiographic predictors of LVMT formation, and the intermediate
      term outcomes of patients with LVMT. METHODS: We retrospectively analysed
      patients (in the years 1997-2002) with a diagnosis of anterior ST-elevation AMI
      and no prior AMI, and who underwent a thorough echocardiographic assessment
      within 72 h of admission. Stepwise logistic regression analysis was used to
      define predictors of LVMT formation. Survival was calculated by the Kaplan-Meier
      product-limit method. RESULTS: Of the 153 patients with complete data, LVMT was
      detected in 36 (23.5%). There were no significant differences in baseline
      demographic and clinical variables between LVMT and non-LVMT patients, or in
      treatments (all patients received reperfusion treatment). The mean wall motion
      score index was higher in LVMT than non-LVMT patients (0.88+/-1.79 versus 0.65+/
      0.36, respectively; P=0.01), indicating worse cardiac systolic function. LVMT
      patients were treated with warfarin for 3-6 months. The incidence of death was
      similar between the groups (11.1% for LVMT patients versus 12.8% for non-LVMT
      patients, P=0.79) over a mean follow-up of 71-72 months. The only independent
      predictor found for LVMT occurrence was worse regional wall motion of the apex
      (odds ratio, 2.04, 95% confidence interval, 1.39-3.03; P<0.001). CONCLUSIONS: In
      the contemporary 'real-world scenario', despite aggressive reperfusion treatment
      and anti-aggregant use, the incidence of LVMT remained high after anterior ST
      elevation AMI. LVMT was not related to increased intermediate-term mortality when
      patients were treated with warfarin, and the only predictor of LVMT occurrence
      was regional function of the apex.

PMID- 16000885
TI  - Impaired coronary collateral vessel development in patients with metabolic
      syndrome.
AB  - BACKGROUND: The development of coronary collateral vessels is the physiological
      response of myocardial tissue to hypoxia or ischemia, which results in an
      increase in blood supply to the tissue. However, a lack of collateral vessels or
      the presence of poor collateralization in some patients despite the presence of
      significant coronary stenosis or obstruction and evidence of myocardial ischemia
      suggest that some other factors may affect the development of collateral
      circulation. In the present study we aimed to evaluate coronary collateral
      circulation in patients with metabolic syndrome with advanced coronary artery
      disease and compare the results with those of patients without metabolic
      syndrome. METHOD: The study population comprised 102 patients with metabolic
      syndrome and advanced coronary artery disease (>or=90% diameter stenosis in at
      least one major epicardial coronary artery) and 102 control participants without
      metabolic syndrome who also had >or=90% diameter stenosis in at least one major
      epicardial coronary artery. The diagnosis of metabolic syndrome was based on the
      National Cholesterol Education Program Adult Treatment Panel III clinical
      definition. Coronary collateral vessels were analysed according to the Cohen and
      Rentrop grading system. Both groups were also divided into two additional groups
      according to the Rentrop collateral score as patients with poor collateral
      circulation (Rentrop score 0-1) and good collateral circulation (Rentrop score 2
      3). RESULTS: The mean Rentrop collateral score for patients with metabolic
      syndrome was significantly lower than for those without metabolic syndrome
      (1.38+/-0.79 compared with 1.99+/-1.08, respectively, P<0.001). When two groups
      were compared with respect to poor and good collateral circulation, poor
      collateral circulation was found to be significantly higher in the metabolic
      syndrome group (70% compared with 32%, respectively, P<0.001). Moreover,
      multivariate logistic regression analysis revealed a significant relationship
      between poor collateral circulation and metabolic syndrome (odds ratio=4.29, 95%
      confidence interval=1.73-10.69, P=0.002). CONCLUSION: We have shown for the first
      time that the development of coronary collateral vessels is poorer in patients
      with metabolic syndrome with advanced ischemic heart disease than in control
      participants without metabolic syndrome. Thus, it can be suggested that metabolic
      syndrome is one of the significant factors affecting the development of coronary
      collateral vessels adversely.

PMID- 16000886
TI  - Metabolic syndrome is associated with extension of coronary artery disease in
      patients with non-ST segment elevation acute coronary syndromes.
AB  - BACKGROUND: Metabolic syndrome (MS) comprises a group of factors that are
      associated with increased risk for cardiovascular events. Acute coronary
      syndromes account for the most important part of cardiovascular events with
      considerable morbidity and mortality. We aimed to investigate the association of
      MS with extension of coronary artery disease in patients presenting with non-ST
      segment elevation (NSTE) acute coronary syndromes (ACS). METHODS: Three hundred
      and six consecutive patients (220 men, 86 women patients) with the diagnosis of
      NSTE ACS, who were hospitalized within the first 24 h of their chest pain in the
      coronary care unit, were prospectively enrolled into our study. Patients with
      elevation of troponins (T or I) were classified as NSTE myocardial infarction
      (MI) and otherwise as unstable angina pectoris (USAP). Components of MS were
      noted as previously identified. Coronary angiograms were evaluated by two
      authors, who were blinded to the study plan and each other, via Sullivan's
      method. RESULTS: MS was noted in 49% of all patients, and was significantly more
      common in women than in men (62.8 versus 43.6%, P=0.003). The mean total stenosis
      score of patients with MS was significantly higher than for those without MS
      (16+/-6 versus 12+/-5, P<0.001), and the mean extension score of patients with MS
      was significantly higher than for those without MS (63+/-29 versus 44+/-26,
      P<0.001). The presence of MS together with some clinical factors and poor total
      cholesterol/high-density lipoprotein cholesterol ratio, hypertension and diabetes
      mellitus, was found to be independently predictive of extension of coronary
      artery disease (CAD) in a group of patients presenting with NSTE ACS.
      CONCLUSIONS: MS is independently associated with CAD extension, and hence, might
      account for poor cardiovascular outcomes through CAD extension in patients with
      NSTE ACS.

PMID- 16000887
TI  - The impact of admission C-reactive protein levels on the development of poor
      myocardial perfusion after primary percutaneous intervention in patients with
      acute myocardial infarction.
AB  - BACKGROUND: Increased preprocedural C-reactive protein (CRP) levels in patients
      with acute myocardial infarction (MI) undergoing primary percutaneous coronary
      intervention (PCI) may affect myocardial perfusion. Accordingly, this study was
      designed to investigate the impact of admission CRP levels on the development of
      poor myocardial perfusion after PCI in patients with acute MI. METHODS: The study
      population consisted of 75 patients (62 men, mean age, 61.6+/-6.68 years), who
      were admitted to our hospital with acute anterior MI and who underwent primary
      PCI in the left anterior descending coronary artery. All patients underwent
      stenting following balloon angioplasty. Myocardial perfusion was evaluated by
      using Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade
      (TMPG). Patients were divided into two groups according to TMPG after PCI. Group
      1 consisted of 25 patients with TMPG 0-1 and group 2 comprised 50 patients with
      TMPG 2-3. Admission serum high sensitive CRP (hs-CRP) levels were analysed by
      using nephelometric method. RESULTS: Admission hs-CRP levels, pain to balloon
      time and white blood cell count (WBC) of patients in group 1 were significantly
      higher than those of the patients in group 2 (P<0.001; P<0.001; P=0.002,
      respectively). Univariate analysis identified ejection fraction, pain to balloon
      time, WBC and hs-CRP levels as the predictors of poor myocardial perfusion. In
      multivariate logistic regression analysis, hs-CRP levels and pain to balloon time
      were found to have statistically significant independent association with poor
      myocardial perfusion. Adjusted odds ratios were calculated as 1.85 for hs-CRP
      [P=0.003; 95% confidence interval (CI), 1.23-2.80] and 5.49 for pain to balloon
      time (P=0.04; 95% CI, 1.08-27.84). CONCLUSIONS: On admission, high CRP level in
      patients with acute MI undergoing primary PCI is likely to be in the causal
      pathway leading to the development of poor myocardial perfusion, especially when
      combined with prolonged pain to balloon time.

PMID- 16000888
TI  - A comparison of two progestins on myocardial ischemia-reperfusion injury in
      ovariectomized monkeys receiving estrogen therapy.
AB  - OBJECTIVE: It has been reported that the progestin medroxyprogesterone acetate
      (MPA), but not norethindrone acetate (NETA), inhibits the beneficial vascular
      effects of post-menopausal estrogen therapy, but their effects on the myocardium
      are unclear. The goal of this study is to compare the effects of these two
      progestins on post-ischemic myocardial damage. METHODS: Ovariectomized monkeys
      were fed an atherogenic diet for 18 months while receiving, or not receiving
      (control, n=15), the monkey equivalent to a woman's dose of 5 mug ethinyl
      estradiol with either 1 mg NETA daily (n=15) or 2.5 mg MPA daily (n=15). The left
      anterior descending coronary artery was occluded for 1 h and then released to
      allow myocardial reperfusion for 4 h. Infarct size was quantified using the
      histochemical stain triphenyl-tetrazolium chloride. Regional myocardial blood
      flow was measured by 15 mum neutron-activated microspheres, blood pressure and
      heart rates with a pneumatic cuff, stroke volume by echocardiography, coronary
      output by thermodilution and neutrophil accumulation in the myocardium using
      myeloperoxidase (MPO) activity. RESULTS: The infarct size (area of necrosis/area
      at risk) was similar between the control group (21+/-3%) and the MPA group (29+/
      3%) (P<0.05) but significantly less in the NETA group (3+/-2%) than other groups
      (P<0.05). The hemodynamic myocardial function and regional myocardial blood
      values were similar among groups before, during and 4 h after reperfusion (all P
      values >0.05). Similarly, there were no treatment effects on MPO activity
      (P>0.05). CONCLUSIONS: NETA, but not MPA, diminished ischemia-reperfusion injury
      in estrogen-treated post-menopausal females. The mechanism(s) of this difference
      remains unclear.

PMID- 16000889
TI  - Long-term prognostic value of ejection fraction changes during dobutamine
      atropine stress echocardiography.
AB  - OBJECTIVE: Dobutamine stress echocardiography (DSE), using subjective wall motion
      scoring, provides incremental prognostic information over clinical data. The aim
      of the study was to test the additional prognostic value of left ventricular
      ejection fraction (LVEF) changes during DSE at different stages. METHODS: The
      study population comprised 106 consecutive patients (mean age 60+/-11 years, 73%
      men) with suspected or known coronary artery disease referred for DSE. Stress
      induced ischemia was defined as new or worsening wall motion abnormalities. LVEF
      was measured at rest, peak stress and recovery. Follow-up was successful in 104
      (98%) patients. Four patients who underwent revascularization within 60 days were
      excluded from the analysis. End-points during follow-up were cardiac death, non
      fatal myocardial infarction and late revascularization. RESULTS: During a mean
      follow-up of 5.3+/-2.1 years, 26% of patients died: 13% due to cardiac death, 6%
      patients experienced non-fatal myocardial infarction and 38% underwent late
      revascularization. Rest-to-peak LVEF increase was lower in patients who
      experienced cardiac death or non-fatal myocardial infarction (4.9+/-8.6 compared
      with 9.2+/-7.5, P=0.04) and any cardiac events (6.0+/-8.5 compared with 10.5+/
      6.7, P=0.004). An inverse correlation was found between left ventricular ejection
      increase and the number of ischemic segments (P<0.0001). A multivariable Cox
      proportional hazard model demonstrated that, in addition to clinical data and new
      wall motion abnormalities, lower LVEF increase had an incremental prognostic
      value in predicting hard cardiac events (hazard ratio 1.1, 95% confidence
      interval 1.0-1.2). CONCLUSION: Failure of LVEF to significantly increase during
      DSE, denoting more extensive ischemia, identifies a higher-risk subgroup for late
      cardiac events.

PMID- 16000890
TI  - Combining different biochemical markers of myocardial ischemia does not improve
      risk stratification in chest pain patients compared to troponin I alone.
AB  - OBJECTIVE: Early evaluation of patients with chest pain is important not only for
      the detection of acute myocardial infarction (AMI) but also for identification of
      patients at high risk for future cardiac events. A multimarker strategy applying
      results of early measurements of different biochemical markers of cardiac
      necrosis in combination may improve risk prediction in chest pain patients.
      METHODS: Rapid measurements of troponin I (TnI), creatine kinase MB and myoglobin
      were performed in 191 consecutive patients with chest pain and a non-diagnostic
      electrocardiogram for AMI. The prognostic value of these markers and different
      multimarker strategies was evaluated and compared. RESULTS: Ten (5.2%) patients
      died during follow-up, which for eight (4.2%) patients was due to cardiac causes.
      Myocardial reinfarctions occurred in 17 (6.8%) patients. TnI was most predictive
      for cardiac mortality (TnI>or=0.1 microg/l, 10.7% event rate compared with
      TnI<0.1 microg/l, 0%, P<0.001) and myocardial reinfarction (14.9% compared with
      1.7%, P<0.001). The other markers and multimarker strategies had a lower capacity
      for predicting adverse events apart from myoglobin and the combination of TnI or
      myoglobin regarding the endpoint of total mortality. CONCLUSION: The combinations
      of different markers were prognostically non-superior compared to TnI, which
      thus, should be preferred as a biochemical marker for risk stratification in
      patients with chest pain.

PMID- 16000891
TI  - The effects of prior use of atorvastatin on coronary blood flow after primary
      percutaneous coronary intervention in patients presenting with acute myocardial
      infarction.
AB  - BACKGROUND: Statins exert a variety of favourable effects on the vascular system
      not directly related to their lipid lowering function known as pleiotropic
      effects. There are not enough data regarding the effects of prior statin use on
      coronary blood flow after percutaneous coronary intervention (PCI) in patients
      with acute myocardial infarction (AMI). Accordingly, in the present study, we
      aimed to investigate the effects of prior statin use on coronary blood flow after
      primary PCI in patients with AMI using the Thrombolysis In Myocardial Infarction
      (TIMI) frame count method. METHODS: The study population consisted of 200
      patients (161 men; mean age=62+/-7 years) referred to cardiology clinics with AMI
      who subsequently underwent successful primary PCI. The study population was
      divided into two groups according to statin use before primary PCI. Group 1
      consisted of 98 patients (75 men; mean age=63+/-7 years) not taking statin and
      group 2 consisted of 102 patients (86 men; mean age=61+/-7 years) taking daily
      dose of at least 40 mg atorvastatin for at least 6 months. Coronary blood flow
      was determined by TIMI frame count method using the angiographic images obtained
      just after PCI and stenting. RESULTS: Only mean TIMI frame count was detected to
      be significantly lower in patients taking at least 40 mg atorvastatin for at
      least 6 months compared with that of the patients taking no statin (P<0.001).
      After confounding variables were controlled for, the mean TIMI frame count of
      patients in group 2 was significantly lower than that of the patients in group 1
      (P=0.001). Pain to balloon time and vessel type were detected as important
      confounding variables of TIMI frame count after analysis of covariances.
      CONCLUSIONS: Prior statin use may improve coronary blood flow after PCI in
      patients with AMI, possibly by its beneficial effects on microvascular function.

PMID- 16000893
TI  - Bibliography: current world literature.

PMID- 16000892
TI  - Use of drug-eluting stents for the treatment of in-stent restenosis in routine
      clinical practice.
AB  - BACKGROUND: Although target lesion revascularization (TLR) has been dramatically
      decreased by using drug-eluting stents (DESs) in de-novo lesions, their efficacy
      for in-stent restenosis (ISR) has not yet been well established. METHODS: We
      retrospectively analysed patients treated for ISR with DESs from three referral
      hospitals. RESULTS: Eighty-seven consecutive patients, from June 2002 to April
      2004, were included, with a mean age of 64+/-11 years; 83% were men, 32% had
      diabetes, 47% had had a previous myocardial infarction and 16% had low left
      ventricular ejection fraction. Angiographic characteristics were as follows: mean
      vessel diameter, 3.05+/-0.4 mm; lesion length, 17.8+/-7.7 mm; diameter stenosis,
      84.0+/-10.7%; and complex lesion, 81%. The restenosis was focal in 45%,
      diffuse/proliferative in 51.3% and total occlusion in 3.7% of the cases.
      Sirolimus- and paclitaxel-eluting stents were used in 42 and 58% of the patients,
      respectively. Stent diameter was 3.1+/-0.3 mm and the length was 26.1+/-5.8 mm.
      Angiographic success was achieved in all patients, with one patient experiencing
      a post-procedural non-Q-wave myocardial infarction. At 6-month clinical follow
      up, two patients had died from non-cardiac deaths, five had experienced a new TLR
      (5.7%, four percutaneous and one coronary artery bypass graft) and eight (9.2%)
      had had major adverse cardiac events. A stress test was performed in 60% of the
      population; target vessel ischemia was observed in one patient (3.3%).
      CONCLUSION: In this non-select cohort of patients, the use of DESs is a safe and
      effective strategy for ISR lesions.

PMID- 16000895
TI  - The Women's Eye Health Task Force.

PMID- 16000896
TI  - Amniotic membrane use in ophthalmology.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the most recent and
      relevant clinical and experimental data about the use of amniotic membrane in
      ophthalmology. RECENT FINDINGS: The amniotic membrane is a biologic tissue that
      has been used as a graft for corneal and conjunctival reconstruction in a variety
      of ocular surface diseases. It is avascular and possesses anti-angiogenetic, anti
      scarring and antiinflammatory properties. It is not a substitute but rather a
      substrate upon which cells can migrate and regenerate, forming new and healthy
      tissue. The amniotic membrane can also be used as a biologic patch, as a bandage,
      to treat acute inflammatory disorders. With the development of cell therapy,
      amniotic membrane can be also used as a carrier of limbal stem cells or their
      progeny, cultivated in vitro. SUMMARY: Amniotic membrane use in ophthalmic
      surgery has been shown to provide an alternative for corneal and conjunctival
      reconstruction in many clinically challenging situations; however, there is still
      a lack of scientific evidence based on randomized comparative studies to prove
      that its use is better than other alternative therapies for ocular surface
      reconstruction.

PMID- 16000897
TI  - Cataract surgery in Fuchs' dystrophy.
AB  - PURPOSE OF REVIEW: Corneal decompensation after cataract surgery can occur in
      patients with Fuchs' endothelial dystrophy. This paper reviews the pathogenesis
      of corneal edema in Fuchs' dystrophy, the preoperative and perioperative risk
      factors for corneal endothelial cell loss during cataract surgery, and
      indications for cataract surgery alone or cataract surgery combined with
      keratoplasty for patients with visually significant cataracts and Fuchs'
      dystrophy. RECENT FINDINGS: Accelerated loss of corneal endothelial cells in
      Fuchs' dystrophy is multifactorial, with apoptosis and altered gene regulation of
      aquaporin proteins playing a role. Preoperative factors contributing to decreased
      endothelial cell count include age, sex, diabetes, a history of ocular trauma or
      inflammation, and contact lens wear. Intra-operative measures shown to protect
      endothelial cells include the use of the soft-shell viscoelastic technique for
      very dense cataracts, efficient cataract removal techniques (phaco-chop, use of
      oscillatory handpiece), and surgery by an experienced surgeon. A triple procedure
      should be performed with preoperative corneal epithelial decompensation and
      considered with preoperative pachymetry greater than 640 mum. Otherwise, it is
      reasonable to attempt cataract surgery alone with proper patient education.
      SUMMARY: Fuchs' dystrophy is a progressive disorder. Cataract surgery in the
      setting of Fuchs' dystrophy can be performed successfully, especially when the
      surgeon is aware of the preoperative and intraoperative factors that affect the
      number of functioning endothelial cells. All patients should be aware of the
      progressive nature of this disease and the possibility of keratoplasty at some
      point in their lifetime.

PMID- 16000898
TI  - Current concepts and techniques in keratoprosthesis.
AB  - PURPOSE OF REVIEW: Diseases affecting the cornea are a major cause of blindness
      worldwide, second only to cataract in overall importance, with an estimated 10 to
      15 million affected people. Although keratoplasty is by far the most successful
      transplantation surgery, the outcomes in high-risk adult patients, including
      those with ocular surface diseases and multiple graft rejections, and in
      pediatric patients with congenital corneal opacities are disappointing. RECENT
      DEVELOPMENTS: Regrettably, no significant clinical developments have been
      achieved in the field of corneal transplantation since the introduction of
      steroids for graft rejection. Furthermore, obtaining donor corneal tissues and
      eye banking, particularly in the developing countries where corneal blindness is
      most prevalent, are problematic. Although the postoperative complications may be
      severe and limit the use of currently available devices, keratoprosthesis-
      artificial corneal implantation--has a role in the management of corneal
      blindness in carefully selected patients with complex ocular diseases who are at
      high risk for graft failure. SUMMARY: This article reviews the recent ophthalmic
      literature published on the current concepts and techniques of keratoprosthesis
      surgery.

PMID- 16000899
TI  - Refractive surgery after corneal transplantation.
AB  - PURPOSE OF REVIEW: Many patients who have undergone corneal transplantation are
      unable to achieve satisfactory visual acuity with spectacle and contact lens
      correction alone. For these patients, refractive surgery becomes a viable option
      to reduce the post-keratoplasty ametropia. With the many recent advances in
      refractive surgery for naturally occurring refractive error, new possibilities
      arise for application to this complicated set of patients. This review discusses
      key recent developments in refractive surgery after corneal transplantation.
      RECENT FINDINGS: The biomechanical effects of incisional keratotomy on post
      keratoplasty corneas continue to be studied, and these techniques remain a common
      and simple method of reducing astigmatism. Photorefractive keratectomy,
      previously problematic for regression and haze formation, is gaining new
      prominence as early experience with the adjunctive use of mitomycin C has
      demonstrated good results. Long-term studies with laser in-situ keratomileusis
      (LASIK) have continued to show good safety and efficacy. Modern developments in
      cataract surgery appear to have lower incidences of graft rejection and failure.
      Developments in lens implantation technology continue to offer expanding options
      for intraocular refractive surgery. SUMMARY: Although visual rehabilitation after
      corneal transplantation remains a formidable challenge, developments in
      refractive surgery for naturally occurring ametropias directly translate into an
      improved ability to help these most challenging refractive cases. Continued
      research will bring about improved efficacy while maintaining a high level of
      safety.

PMID- 16000900
TI  - How and when to use mitomycin-C in refractive surgery.
AB  - PURPOSE OF REVIEW: Mitomycin-C is an antimetabolite that has seen increased use
      in ophthalmology over the past several decades. From glaucoma surgery to the
      management of various corneal disorders, mitomycin-C seems to be a viable tool in
      the management of scar and haze formation. RECENT FINDINGS: With the constant
      evolution of refractive surgery, mitomycin-C has come to the forefront as a
      modulator of corneal wound healing after excimer laser surface ablation. SUMMARY:
      This article will describe the various indications, techniques, and current
      trends of mitomycin-C application in corneal refractive surgery.

PMID- 16000901
TI  - Are intracorneal rings still useful in refractive surgery?
AB  - PURPOSE OF REVIEW: This article reviews the latest data published and presented
      at international meetings about the use of intracorneal ring segments in corneal
      and refractive surgery. RECENT FINDINGS: The long-term data on intracorneal ring
      segments in the correction of low to moderate myopia indicate that they seem
      clearly comparable with laser in-situ keratomileusis, the most common refractive
      procedure worldwide. There is increasing interest in the use of intracorneal ring
      segments for the treatment of some complications after laser in-situ
      keratomileusis and for the control of some degrees of primary corneal ectatic
      disorders such as keratoconus and pellucid marginal degeneration. SUMMARY:
      Intracorneal ring segments are and will be useful in several corneal and
      refractive abnormalities. Concern still exists about their predictability and the
      long-term effects of their use in primary and secondary ectasia.

PMID- 16000902
TI  - Bibliography. Current world literature.

PMID- 16000907
TI  - Evaluating the patient with chest pain: the value of a comprehensive history.
AB  - Chest pain is one of the most common presenting symptoms in healthcare settings
      and one of the most difficult diagnostic challenges. A comprehensive history is
      the cornerstone of evaluation and diagnosis and one of the most important skills
      in distinguishing among the many causes of chest pain. Because the differential
      diagnosis for chest pain ranges from conditions as minor as muscle strain to life
      threatening conditions, such as an acute myocardial infarction or dissecting
      thoracic aortic aneurysm, the advanced practice nurse must quickly and
      systematically assess the patient.

PMID- 16000908
TI  - Chest pain and associated symptoms of acute coronary syndromes.
AB  - Coronary heart disease is the primary health risk for all Americans. Acute
      coronary syndromes (ACS) is the term used to denote any 1 of 3 clinical
      manifestations of coronary heart disease: unstable angina, non-ST elevation
      myocardial infarction, and ST-elevation MI. The major challenge to healthcare
      providers is the rapid and accurate identification of patients with ACS who would
      benefit from immediate thrombolysis or percutaneous coronary interventions. The
      purpose of this article is to describe the incidence, causes, risk factors,
      assessment, and diagnosis of patients presenting with ACS as well as current
      recommendations for nurses who treat patients with ACS.

PMID- 16000909
TI  - Pericarditis: inflammation or infarction?
AB  - Pericarditis occurs when there is inflammation of the pericardium, a 2-layer sac
      that surrounds the myocardium. These layers are separated by 15 to 20 mL of thin
      serous fluid. The accumulation of serous fluid along with the presence of
      inflammatory cells and fibrin can compromise cardiac function. The cause of
      pericarditis can be related to many disorders and often mimics signs of
      myocardial ischemia or acute myocardial infarction (AMI). Complications such as
      cardiac tamponade can occur with a large effusion and can be life threatening. It
      is essential to differentiate pericarditis from AMI. Preservation of heart muscle
      in AMI is essential as is proper treatment and prevention of complications such
      as cardiac tamponade, which can occur as a result of pericarditis. This article
      discusses the common causes, clinical manifestations, diagnostic procedures, and
      treatment associated with pericarditis.

PMID- 16000910
TI  - Thoracic aortic aneurysms.
AB  - Thoracic aortic aneurysm with dissection is the most common fatal condition
      involving the aorta. The prevalence of aortic aneurysms appears to be increasing,
      which may reflect improvements in imaging techniques as well as increased
      clinical awareness of the condition. Most thoracic aortic aneurysms are caused by
      atherosclerosis and its associated risk factors of hypertension, smoking, and
      hypercholesterolemia. The clinical presentation varies and may mimic other more
      common disease processes. Early recognition on the basis of a focused history,
      physical examination, appropriate diagnostic studies, and management is essential
      for good outcomes.

PMID- 16000911
TI  - Pneumothorax: assessment and diagnostic testing.
AB  - Acute pneumothorax and the presence of air in the pleural space, is a relatively
      common and potentially life-threatening cause of chest pain. Early recognition
      and treatment are essential in decreasing the morbidity and mortality from this
      condition. Knowledge of the diseases and procedures associated with an increased
      risk for pneumothorax, as well as the frequent signs and symptoms upon
      presentation, will assist the clinician in its early identification.

PMID- 16000912
TI  - Early recognition of pulmonary embolism: the key to lowering mortality.
AB  - Pulmonary embolism is a major cause of morbidity and mortality in the United
      States. The majority of deaths from pulmonary embolism occur because an accurate
      diagnosis was not made. It is imperative for clinicians to have a high level of
      clinical suspicion of pulmonary embolism when patients present with dyspnea,
      tachypnea, chest pain, hemoptysis, and cough. If pulmonary embolism is diagnosed
      and treatment initiated, death and recurrence of embolism are uncommon. Beyond
      correct diagnosis and treatment, the single most effective strategy that can be
      employed to decrease the high mortality associated with pulmonary embolism is
      identification of individuals at risk and the institution of prophylactic
      measures. This article reviews the incidence, risk factors, assessment, physical
      examination, laboratory, and diagnostic testing for pulmonary embolism.

PMID- 16000914
TI  - Update on implantable pacemakers.
AB  - There are currently more than 3 million patients worldwide with implanted
      pacemakers, and indications for implants are expanding. Pacemakers today are
      smaller (23-30 g) and fashioned in a more physiologic shape so as to be less
      obtrusive. They are replete with sophisticated diagnostic and programming
      features that make troubleshooting of complicated arrhythmias easier. Advanced
      nurse clinicians need to have a basic understanding of pacemaker function,
      indications for implantation, an awareness of potential complications, and
      facility with basic troubleshooting. The purpose of this article is to describe
      the features of the pacemakers available today and approaches to troubleshooting
      these devices.

PMID- 16000916
TI  - A case report of pacemaker lead perforation causing late pericardial effusion and
      subacute cardiac tamponade.
AB  - Despite medical therapy, the overall prognosis for heart failure (HF) remains
      poor with high rates of sudden death and death from progressive HF. Device-based
      therapies offer considerable promise both for the relief of symptoms and for
      improving prognosis. Cardiac resynchronization therapy is a relatively new and
      effective treatment for patients with moderate to severe systolic HF and
      ventricular dyssynchrony. Clinical trials have demonstrated an improvement in
      quality of life, improved exercise tolerance, decreased HF hospitalizations, and
      improved survival. Complication rates for patients receiving cardiac pacemakers
      are relatively low. Although rare, cardiac tamponade caused by myocardial
      perforation during pacing lead insertion usually occurs a short time after the
      procedure. This case study discusses a patient who presented with cardiac
      tamponade 4 months after pacemaker implant. A small perforation of the right
      atrial lead caused a slow effusion into the pericardial sac. The patient's
      unusual presentation, hospital course, pathophysiology, and treatment for cardiac
      tamponade are discussed.

PMID- 16000917
TI  - Implantable cardioverter defibrillator therapy.
AB  - Sudden cardiac death (SCD) is a major healthcare problem worldwide. The majority
      of SCD events occur in patients with clinically recognized heart disease and most
      episodes result from ventricular tachyarrhythmias. Implantable cardioverter
      defibrillator (ICD) therapy prevents SCD in specific patient populations.
      Significant progress in the design and technology has been made since the Food
      and Drug Administration first approved the ICD in 1985. First-generation ICDs
      were large, were implanted in the abdomen, required a thoracotomy for placing
      epicardial defibrillation patches, and were nonprogrammable. Contemporary ICDs
      have been substantially downsized, are implanted via a transvenous approach, and
      are multiprogrammable. Device implantation has been simplified to be similar to
      that of a permanent pacemaker. In addition to treating life-threatening
      ventricular arrhythmias, ICDs now treat bradyarrhythmias, atrial arrhythmias, and
      congestive heart failure. The purpose of this article is to describe the evidence
      supporting the use of ICD therapy and to explain the current devices used in
      clinical practice.

PMID- 16000918
TI  - Psychological disturbances, adjustment, and the development of phantom shocks in
      patients with an implantable cardioverter defibrillator.
AB  - The implantable cardioverter defibrillator (ICD), approved for use in 1985, is
      used to treat potentially lethal ventricular arrhythmias by delivering an
      electrical impulse to the heart to convert the rhythm back to normal. Since that
      time, newer studies, such as MADIT II and SCD-HeFT, demonstrated the expanding
      utility of the ICD, which increases the likelihood of every clinician
      encountering a patient with an ICD. Patients with an ICD face psychological,
      physical, and social adjustments. Patients with an ICD, in general, have been
      shown to have high levels of anxiety, depression, and a sense of helplessness. A
      subset experiences a phenomenon of phantom shock, which may represent a
      manifestation of anxiety, depression, or other emotional disturbance. It is
      important to be aware of this phenomenon, as a phantom shock may either represent
      or contribute to the patient's maladjustment to the ICD. In lieu of specific
      screening and treatment options for phantom shock at present, we must use a
      general approach for recognizing patients experiencing this phenomenon.

PMID- 16000919
TI  - Choosing our battles in the overweight/obesity crisis: targeting those who have
      the most to gain by losing.

PMID- 16000920
TI  - High-frequency mini-probe ultrasound: the Rodney Dangerfield of endoscopy?

PMID- 16000921
TI  - Update in medical therapy of ulcerative colitis: newer concepts and therapies.
AB  - Recent advances in the pathogenesis of ulcerative colitis recognize the interface
      of genetic susceptibility, environmental factors (eg, gut microflora), and an
      altered host's immune response. The meteoric evolution of new therapies designed
      to address these pathogenetic factors may lead to confusing and often confounding
      treatment programs. This review is designed to assist the practitioner when in
      [corrected] incorporating new or novel therapies into a treatment program. These
      decisions are based on new clinical trial data and the experience of seasoned
      gastroenterologists with established remedies. NEWER CONCEPTS AND THERAPIES IN UC
      5-ADA-- 1. Remains drug of choice for induction and maintenance of remission in
      mild to moderate IC.1,2 2. Rare but increased incidence of renal disease exists
      but benefits outweigh risks.18-20 3. Chemoprevention of colorectal cancer in UC
      is promising and may be related to higher dose and a lessened degree of
      inflammation.29-36 4. Bioequivalence of all USA 5-ASA is established. Choice of a
      5-ASA preparation is not dependent on superiority of a particular mesalamine.3
      Phosphodiesterase Inhibitor (OPC-6525)37: preliminary data promising
      Immunomodulators 6MP/AZA 1. long-term effect not waning51 2. concerns over
      lymphoma voiced but overall benefits outweigh risks64-70 3. 6MP metabolites
      measurements of increasing use52-56 Cyclosporine experience continues but serious
      adverse events remains.105-114 Biologics Infliximab--somewhat disappointing in
      CUC, awaiting RCT87-92 Basiliximab--useful as "steroid sensitizer" in previously
      steroid resistant patients118-120 Visilizumab--promising as alternative to
      cyclosporin in server U.C.115-117 Apheresis--and emerging "non-drug" treatment
      alternative121-135 Probiotics--Useful in pouchitis and some mild to moderate
      U.C.94-98, 154 ISIS topical therapy useful in early pilot study (pouchitis)151
      Budesonide (pouchitis)147 Antibiotics (pouchitis)140-146 [corrected]

PMID- 16000922
TI  - How to predict the future (outcome of gastrointestinal disease).
AB  - This short review is aimed to illustrate three simple rules to predict the
      outcome of a gastrointestinal disease. The first rule relates to the principle of
      WYSIWYG, that is, "what you see is what you get." To predict the future of a
      given digestive disease, the gastroenterologist needs to pay close attention to
      its present appearance and develop clear understanding of its pathophysiology. To
      delineate future trends, as a second rule, the gastroenterologist needs to
      delineate past trends and try to extrapolate them into the near future. Third,
      the length of the past medical history also provides a reliable estimate for the
      expected future lifetime of a gastrointestinal disease. These rules enable
      gastroenterologists to enlighten themselves, as well as their patients, about the
      future outcome of a given gastrointestinal disease.

PMID- 16000923
TI  - A prospective study of the diagnostic accuracy of PillCam ESO esophageal capsule
      endoscopy versus conventional upper endoscopy in patients with chronic
      gastroesophageal reflux diseases.
AB  - INTRODUCTION: Endoscopy is commonly performed to evaluate for suspected or
      established esophageal diseases including gastroesophageal reflux disease (GERD)
      and its complications. The newly developed PillCam ESO Esophageal Capsule offers
      an alternative approach to visualize the esophagus and to evaluate patients with
      suspected esophageal disease. AIM: Compare the accuracy (specificity,
      sensitivity, positive predictive value [PPV], and negative predictive value
      [NPV]) of esophageal capsule endoscopy (ECE) compared with
      esophagogastroduodenoscopy (EGD) in evaluating patients with GERD. METHODS: A
      multicenter pivotal trial was conducted at seven sites. The PillCam ESO
      esophageal capsule is similar to the standard capsule endoscope used for the
      small bowel but acquires video images from both ends of the device at 2
      frames/second/end. A total of 106 patients (93 GERD; 13 Barrett) underwent ECE
      followed by EGD. ECE videos were evaluated by an investigator blinded to EGD
      findings. A blinded adjudication committee reviewed all discrepant findings
      between ECE and EGD. RESULTS: Sixty-six of 106 patients had positive esophageal
      findings, ECE identified esophageal abnormalities in 61 (sensitivity, 92%;
      specificity, 95%). The per-protocol sensitivity, specificity, PPV, and NPV of ECE
      for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for
      esophagitis 89%, 99%, 97%, and 94%, respectively. ECE was preferred over EGD by
      all patients. There were no adverse events related to ECE. CONCLUSIONS: ECE is a
      convenient and sensitive method for visualization of esophageal mucosal pathology
      and may provide an effective method to evaluate patients for esophageal disease.

PMID- 16000924
TI  - Nighttime reflux is primarily an early event.
AB  - GOALS: Our clinical impression gleaned from reading large numbers of ambulatory
      pH studies is that recumbent reflux episodes mostly occur in the early part of
      the nighttime period. In this study, we propose to test this hypothesis. STUDY: A
      total of 201 consecutive pH studies performed in our laboratory between November
      2001 and October 2002 were analyzed. Population characteristics: 75 males and 126
      females; mean age, 50.4 yrs (range, 16-88 years). Reflux was defined by a drop in
      pH to less than 4. Abnormal total recumbent reflux was defined as >1.2% time pH <
      4. For patients with abnormal recumbent reflux, the recumbent period was divided
      into two halves and the reflux time in each period was calculated. In all
      patients, ingestion of a meal within 2 hours of retiring was also identified.
      RESULTS: A total of 59 patients had abnormal recumbent reflux: 24 males and 35
      females; mean age, 48.9 years. In patients with abnormal recumbent reflux, acid
      reflux was significantly more frequent in the first half of the recumbent period
      compared with the second half (median, 6.3%; vs. 0.3%, respectively; P < 0.001;
      Wilcoxon signed rank test, two-tailed analysis). Those patients (N = 118) having
      had a meal within 2 hours of retiring were 2.46 times more likely to develop
      recumbent reflux than those whose last meal was more than 2 hours earlier (N =
      83). CONCLUSION: These results support our hypothesis that nighttime reflux
      occurs primarily during the first half of the recumbent period. In addition, they
      reinforce the concept of maintaining control of early nighttime reflux and the
      importance of counseling patients with nocturnal symptoms against late meals and
      snacks.

PMID- 16000925
TI  - Esophageal manometry and pH monitoring: gastroenterologists' adherence to
      published guidelines.
AB  - GOALS: To determine whether gastroenterologists use esophageal manometry (EM) and
      esophageal pH recording (pHR) in accordance with published guidelines. STUDY:
      Questionnaires were mailed to 900 randomly selected gastroenterologists
      nationwide. Each questionnaire requested demographic information and contained 11
      case scenario-based questions, followed by a choice of management options.
      RESULTS: A total of 275 completed questionnaires (30.6%) were returned. 63.6% and
      64.4% of respondents were aware of published guidelines regarding the use of EM
      and pHR, respectively. The majority of respondents ordered EM appropriately: 1)
      to confirm a suspected diagnosis of achalasia (97.1%); 2) to establish a
      diagnosis of connective tissue disease (89.7%); 3) as part of the preoperative
      evaluation for anti-reflux surgery (74.6%); and 4) to ensure the proper placement
      of pH probes (69.4%). EM was rarely ordered for the initial workup of noncardiac
      chest pain. The majority of responding gastroenterologists would order pHR for
      the evaluation of: 1) endoscopy-negative patients being considered for anti
      reflux surgery (79.1%); 2) patients with recurrent GERD symptoms after anti
      reflux surgery (62.5%); 3) endoscopy-negative patients with GERD symptoms
      refractory to proton pump inhibitor (PPI) therapy; and 4) patients with
      extraesophageal manifestations of GERD that are refractory to PPI therapy
      (88.7%). CONCLUSIONS: The majority of gastroenterologists in our study order EM
      and pHR in accordance with published guidelines. However, EM appears to be used
      less than expected for preoperative evaluation before anti-reflux surgery and for
      ensuring the proper placement of pH probes. In addition, the use of pHR to
      evaluate persistent GERD symptoms after anti-reflux surgery was less than
      anticipated.

PMID- 16000926
TI  - Small intestinal contrast ultrasonography-based scoring system: a promising
      approach for the diagnosis and follow-up of celiac disease.
AB  - BACKGROUND: Small intestinal ultrasonography with anechoic contrast agents
      (SICUS) has been shown to have a diagnostic accuracy on small bowel morphology
      similar to X-ray barium follow-through. Although extremely investigated by
      transabdominal ultrasonography, celiac disease, a common disorder of the small
      bowel, has been never studied by SICUS. AIM: To asses SICUS characteristics of
      celiac disease patients. PATIENTS AND METHODS: SICUS was performed using PEG 4000
      as contrast agent. Twenty-three patients with celiac disease at the first
      diagnosis were enrolled and 30 healthy volunteers, matched for sex and age, were
      selected as control group. Celiac disease diagnosis was based on anti-gluten,
      anti-endomysium, and anti-transglutaminase positivity as well as jejunal
      histology. The following seven echographic parameters were considered: liquid
      endoluminal content before contrast, loop diameter, Kerckring's folds,
      peristaltic waves, ileal jejunalization, mesenteric lymphoadenomegaly, and
      Doppler resistance index (RI) of mesenteric superior artery. Statistical analysis
      was performed by Student's t test for unpaired data; one-way analysis of variance
      was used to correlate echographic and histologic pictures. RESULTS: Loop
      diameter, Kerckring's fold number, peristaltic waves, and Doppler RI appeared to
      be significantly different between celiac disease patients and controls.
      Additionally, liquid content, ileal jejunalization, and mesenteric
      lymphoadenomegaly were present only in the celiacs (52.1%, 47.7%, and 95.6%,
      respectively), but not in controls. Only Doppler RI values significantly
      correlated with the histologic degree of damage. CONCLUSIONS: SICUS could be a
      reliable and noninvasive technique to confirm a diagnosis of celiac disease
      performed using conventional investigations. The possibility of investigating the
      whole small bowel and the safety of repeating examinations could be useful in the
      follow-up of celiac patients.

PMID- 16000927
TI  - 20-MHz high-frequency endoscopic ultrasound-assisted endoscopic mucosal resection
      for colorectal submucosal lesions: a prospective analysis.
AB  - GOALS: To prospectively assess the safety and efficacy of high-frequency
      ultrasound assisted mini-probe endoscopic mucosal resection for the treatment of
      colorectal submucosal tumors. Primary endpoints were tumor free
      vertical/horizontal resection margins and positive histopathologic diagnosis.
      Outcome data over a 24-month period were assessed. BACKGROUND: A 20-MHz high
      frequency mini-probe ultrasound is an accurate modality for the diagnosis of
      stage T1m and T1 colorectal lesions. Few studies have addressed the safety and
      efficacy of this technology as applicable to submucosal lesions of the
      colorectum. METHODS: Thirty patients underwent high-frequency mini-probe
      ultrasound-guided endoscopic mucosal resection of 30 lesions (<20 mm diameter)
      using the inject and cut technique. Repeat endoscopy and ultrasound was performed
      at 3, 6, and 12 months post-"index" resection. RESULTS: A total of 27 lesions
      (90%) underwent complete resection with negative histologic margin status (median
      diameter, 8 mm; range, 3-20 mm). No statistical difference (P > 0.1) was observed
      between submucosal lesion position and histologic resection margin negativity.
      Three rectal lesions (10%) within the submucosal layer 3 failed to separate from
      the muscularis and underwent transanal excision of tumor. Bleeding occurred in 1
      patient (3%). No recurrence was evident at the resection site in 27 cases (median
      follow-up, 9 months; range, 4-18 months). CONCLUSIONS: High-frequency mini-probe
      ultrasound-guided endoscopic mucosal resection is a safe and effective
      therapeutic modality for submucosal lesions of the colorectum. The technique
      offers a single-stage diagnostic and therapeutic technique for selected
      submucosal lesions and may offer an alternative to surgical resection.

PMID- 16000928
TI  - Lack of lasting effectiveness of PEG 3350 laxative treatment of constipation.
AB  - PURPOSE: PEG 3350 (MiraLax, Braintree Laboratories Inc., Braintree, MA) 17 g
      daily has been shown to be safe and effective in a 14-day trial for constipation.
      This present investigation was designed to extend the treatment and safety
      experience with PEG 3350 and to evaluate any lasting effectiveness during a 30
      day post-treatment observation period. METHODS: Study subjects met Rome II
      criteria for constipation and reported <3 bowel movements a week. They were
      treated with PEG 3350 17 g daily for 14 days. Treatment efficacy was defined by
      resolution of constipation symptoms as determined by the Rome II and stool
      frequency definitions during the treatment period. RESULTS: Fifty healthy
      constipated subjects formed the study group. There were 42 females and 8 males.
      Mean age was 52 +/- 15.5 years (+/-SD). Symptom duration was 22.6 +/- 16.7 months
      (+/-SD). At baseline, all had <3 bowel movements a week and met Rome II criteria.
      Two were lost to follow-up. Two took enemas or laxatives and 2 discontinued
      active treatment because of "gas" and were considered treatment failures. At the
      end of 14 days, 40 of 48 (83.3%) had >3 stools in the last week and no longer met
      Rome criteria. Thirty-two of 45 (71.1%) reported satisfaction with the first
      bowel movement after initiating treatment. Thirty days after active treatment, 29
      of 47 (61.7%) responded that they needed laxative treatment. CONCLUSION: PEG 3350
      relieved constipation in most treated study subjects. During a 30-day post
      treatment observation period, 29 of 47 (61.7%) had additional constipation
      treatment interventions.

PMID- 16000929
TI  - Liver biopsy: evolving role in the new millennium.
AB  - Since the origination of the liver biopsy, the technique has evolved into an
      essential diagnostic tool, with very few complications. In addition to the
      percutaneous approach, a liver biopsy can also be obtained via transjugular,
      laparoscopic, or intraoperative approach. While in the early 1960s and 1970s the
      liver biopsy was used for making a diagnosis in cases of clinically suspected
      medical liver disease, today it is more often performed to assess disease
      prognosis and evaluate therapeutic strategies. As a result, indications for the
      liver biopsy have evolved over the past 2 decades. However with advances in
      serologic diagnosis of viral/autoimmune hepatitis and laboratory tests for
      genetic disorders, the role of liver biopsy in certain clinical settings is
      currently debated. This review discusses the technique, indications,
      contraindications, and the changing role of liver biopsy in some of the common
      disorders and the associated controversies.

PMID- 16000930
TI  - Genotypic variability of hepatitis viruses associated with chronic infection and
      the development of hepatocellular carcinoma.
AB  - At least five hepatitis viruses are known to date. Infection by enterically
      transmitted viruses (HAV and HEV) is generally benign compared with the disease
      caused by parenterally transmitted viruses (HBV, HCV, and HDV). Chronic infection
      by HBV is common and may evolve to cirrhosis and hepatocellular carcinoma (HCC).
      Eight HBV genotypes (A-H) have been described, with the South American genotype F
      being the most divergent. Seven clades of HDV have been described; among them,
      the South American genotype III is associated to a high frequency of fulminant
      hepatitis. HCV infection leads to a high rate of chronicity and HCC. From the six
      HCV genotypes, infection with genotype 1 might have the worst prognostic. Chronic
      infection by HCV and HBV is the major risk factor for HCC, which occurs, in the
      majority of the cases, as a consequence of cirrhosis. However, there is growing
      evidence that some HBV and HCV proteins might contribute to the generation of
      HCC. Some HBV and HCV variants and specific mutations within the viral genomes
      might be more frequently associated with the evolution to HCC. Although more
      studies are needed, emerging evidence indicates that it might be important to
      address the genetic variability of these viruses and their contribution to the
      development of HCC.

PMID- 16000931
TI  - Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis,
      and ultrasound.
AB  - PURPOSE: The value of MRI and ultrasound in quantifying hepatic steatosis is
      assessed and the results compared with those obtained by liver biopsies. METHODS:
      A total of 38 patients undergoing hepatic biopsy for a variety of liver diseases
      were recruited for this study. Hepatic fat morphology and severity were assessed
      visually in each biopsy specimen. Steatosis pattern included macrovesicular,
      microvesicular, or mixed. The severity of hepatic steatosis was assessed by MRI
      through chemical shift imaging (n = 38) and by ultrasound through echogenicity (n
      = 31). RESULTS: MRI had a better correlation than ultrasound for microscopic fat
      content (r = 0.77, P < 0.001 vs. r = 0.41, P < 0.05). In macrovesicular
      steatosis, MRI and ultrasound both correlated well with microscopic fat content
      (r = 0.92, P < 0.001 vs. r = 0.90, P < 0.001). In nonalcoholic fatty liver
      disease, ultrasound revealed severe steatosis in all instances, but MRI fat
      content ranged greatly (19%-40%). In diagnoses excluding nonalcoholic fatty liver
      disease, increasing ultrasound severity did not correspond to advanced MRI fat
      content. CONCLUSION: Hepatic MRI and ultrasound are both useful in identifying
      heavy fat accumulation associated with nonalcoholic fatty liver disease. MRI is
      superior to ultrasound in detecting and quantifying minor degrees of fatty
      metamorphosis in the liver.

PMID- 16000932
TI  - Band ligation plus sclerotherapy versus sclerotherapy alone in children with
      extrahepatic portal venous obstruction.
AB  - Although endoscopic band ligation (EVL) plus sclerotherapy (EST) has shown to be
      superior to any individual method, there is no study in children. We therefore
      analyzed our experience of EST and EVL + EST in children with extrahepatic portal
      venous obstruction (EHPVO). Over a period of 8 years, 136 children who presented
      with a history of recent variceal bleeding due to EHPVO were studied; 30 of them
      received EVL + EST and 106 received EST alone. In the EVL + EST group, after the
      first session of EVL, EST was done three times weekly until variceal eradication
      was achieved. The mean age of these children was 7 +/- 3.6 years with a male-to
      female ratio of 2.6:1. The rate of eradication was comparable in both groups
      (100% in EVL + EST and 96% in EST). However, EVL + EST group required a
      significantly fewer sessions and lower volume of sclerosant (2 +/- 1 vs. 4.4 +/-
      2 sessions, P < 0.001 and 3.1 +/- 2 mL versus 7.5 +/- 4 mL, P < 0.001
      respectively). There were significantly less complications in EVL + EST group
      (10% vs. 36%, P < 0.01). Over a mean follow-up of 27 months, varices recurred in
      6.6% and 10% cases, respectively. EVL + EST is a better method in the treatment
      of esophageal varices in children with EHPVO than EST alone, as it required fewer
      session and had fewer complication.

PMID- 16000933
TI  - Cirrhosis in children with celiac disease.
AB  - BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac
      disease (CD) and shows a clinical spectrum varying from nonspecific reactive
      hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5
      children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8
      years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out.
      Intestinal and liver biopsies were performed to confirm the histologic diagnosis
      in all subjects. RESULTS: Three of the patients had chronic diarrhea and
      hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at
      presentation simultaneously. In the other 2 patients, CD was diagnosed following
      an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range,
      64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were
      elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum
      aminotransferase levels and clinical improvement were observed in 3 patients with
      strict GFD. The other 2 patients without improvement of the liver disease had
      poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic
      damage in children and strict GFD may have beneficial effect on the course of
      liver disease. Serologic screening of CD should be included in differential
      diagnosis of chronic liver disease of unknown origin.

PMID- 16000934
TI  - Outcome following endoscopic transmural drainage of pancreatic fluid collections
      in outpatients.
AB  - OBJECTIVE: To evaluate the performance of endoscopic transmural drainage of
      pancreatic fluid collections (PFCs) in outpatients. PATIENTS AND METHODS: We
      retrospectively reviewed 19 consecutive outpatient cases in 18 patients who
      underwent attempted endoscopic transmural drainage of PFCs by a single
      endoscopist at the Mayo Clinic in Rochester, MN, over a 5-year period (October
      1998 to October 2003). All drainages were performed without EUS-guided entry,
      using an aspiration needle and no cautery. Two 10-Fr stents were placed after
      dilation of the entry site. RESULTS: The study group consisted of 12 men and 6
      women (median age, 48 years; range, 28-79 years), with 14 cases of pseudocysts
      and 5 cases of pancreatic necrosis. Transmural drainage approaches included 13
      transgastric, 5 transduodenal, and 1 combined transgastric/transpapillary.
      Drainage was established in 16 of 19 (84%) cases. Hospitalization was noted in 6
      of 19 (32%) cases, with median hospitalization duration of 1.5 days (range, 1-19
      days). Three patients were hospitalized for overnight observation only. In all
      instances, the decision to hospitalize was made while the patient was still in
      recovery. No deaths occurred. Follow-up imaging was available in 15 of 16 (94%)
      cases in which drainage was established, demonstrating PFC resolution in all 15.
      CONCLUSIONS: Endoscopic transmural drainage of PFCs can be performed safely and
      effectively in selected outpatients. It is our opinion that outpatient drainage
      of PFCs be considered only by experienced therapeutic endoscopists with readily
      available inpatient facilities. Future studies should seek to identify predictors
      of hospitalization and address cost-effectiveness.

PMID- 16000935
TI  - Hepatic injury in a patient taking rosiglitazone.
AB  - We describe a 52-year-old man with type 2 diabetes mellitus who developed
      cholestatic hepatitis in association with rosiglitazone use. Liver biopsy
      findings included dilated canaliculi, inspissated bile, intrahepatocellular bile
      pigment deposits, and enlarged xanthomatous Kupffer cells. The form of liver
      injury reported in this case differs markedly from those reported previously for
      rosiglitazone.

PMID- 16000936
TI  - Acute hepatitis associated with alosetron (Lotronex).
AB  - Alosetron hydrochloride (Lotronex, GlaxoSmithKline, Inc) is a safe and effective
      agent for selective patients with severe irritable bowel syndrome when prescribed
      as recommended. We describe the first reported case of acute liver injury in a 39
      year-old white woman who developed symptomatic hepatitis 28 days after starting
      alosetron. All other competing causes of acute hepatitis were excluded by
      radiologic and laboratory studies and the liver injury resolved after drug
      discontinuation. Although the mechanism of alosetron hepatotoxicity is unknown,
      metabolic idiosyncrasy is suspected since the drug is known to be extensively
      metabolized by cytochrome-P450 enzymes. Clinicians prescribing alosetron should
      be aware of this potential side effect if unexplained abdominal pain, jaundice,or
      abnormal liver biochemistries are encountered in a treated patient.

PMID- 16000937
TI  - Sildenafil prescribed for erectile dysfunction may induce esophageal symptoms.

PMID- 16000939
TI  - Valsalva retinopathy as a complication of colonoscopy.

PMID- 16000940
TI  - Beclomethasone dipropionate plus VSL#3 for the treatment of mild to moderate
      diverticular colitis: an open, pilot study.

PMID- 16000941
TI  - Postpartum severe portal vein thrombosis and pyogenic liver abscess.

PMID- 16000942
TI  - Videocapsule impaction in a Zenker's diverticulum.

PMID- 16000943
TI  - Acute obstruction of the celiac trunk.

PMID- 16000944
TI  - Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors:
      current status and future directions.
AB  - Although myeloablative conditioning can cytoreduce or debulk malignancies, the
      curative antitumor effects of allogeneic hematopoietic stem cell transplantation
      (HCT) are mostly mediated by transplanted donor immune cells. A heightened
      awareness and appreciation of the immune-mediated anticancer effects that occur
      after allogeneic transplantation has led to the increasing use of reduced
      intensity stem cell transplantation (RIST) approaches to treat advanced
      malignancies. The graft-versus-leukemia effects that occur against hematologic
      cancers after RIST have recently attracted oncologists to explore the therapeutic
      potential of allogeneic HCT for treatment-refractory solid tumors. Delayed tumor
      regression after RIST in a subset of patients with metastatic renal cell, breast,
      ovarian, pancreatic, and colon carcinoma has recently been reported, confirming
      the existence of a graft-versus-tumor effect in solid tumors. Advanced disease
      states, rapidly growing tumors, and accrual of patients with extremely short
      survival are factors that have been identified to limit the efficacy of
      allogeneic immunotherapy. This review discusses results of allogeneic HCT for
      solid tumors and the development of newer transplant strategies to optimize the
      potential of the graft-versus-tumor effect.

PMID- 16000945
TI  - Cytokine signals in T-cell homeostasis.
AB  - Thymic production of T cells declines rapidly with age, and therefore homeostatic
      cycling (HC) of mature lymphocytes plays an important role in maintaining stable
      numbers of mature T lymphocytes bearing sufficient repertoire diversity.
      Following lymphocyte depletion, HC changes in quality and magnitude, resulting in
      homeostatic peripheral expansion (HPE), a state of widespread T-cell cycling that
      serves to increase T-cell number and to maintain T-cell repertoire diversity to
      the greatest extent possible. Recent studies delineating the requirements for HC
      and HPE have shown that naive CD4+ cells and naive CD8+ cells require both IL7
      and TCR engagement for survival, cycling, and homeostatic expansion, whereas CD8+
      memory cells are maintained and expanded by cytokine signals alone, independent
      of TCR engagement. While basal levels of IL15 are sufficient for HC and HPE of
      CD8+ memory cells, supranormal levels of IL7 will also suffice. The requirements
      for memory CD4+ cells remain unclear, but current models hypothesize that either
      IL7 or TCR triggering may be sufficient. Thus, the changes in immune physiology
      that are present in lymphopenic hosts can be largely accounted for by cytokine
      driven signals, especially those rendered by IL7 or IL15. As the alterations in
      immune physiology present in lymphopenic hosts may be conducive to stronger
      antitumor immune responsiveness, careful delineation of the factors responsible
      may be expected to give rise to approaches to augment the effectiveness of
      current antitumor immunotherapies.

PMID- 16000946
TI  - CD8-based T cell vaccination and CD4 T cell responses in prostate cancer.

PMID- 16000947
TI  - Rapid assessment of recognition efficiency and functional capacity of antigen
      specific T-cell responses.
AB  - It is increasingly recognized that cells within an antigen-specific CD8 T-cell
      population may be diverse in recognition efficiency for target, which may
      significantly affect the overall efficacy of the response in clinical settings
      such as viral infections and cancer. CD8 T cells with seemingly identical antigen
      specificity, particularly those elicited by cancer vaccines, may be heterogeneous
      for sensitivity and recognition efficiency for the cognate peptide and functional
      state in vivo. Analysis of individual T-cell clones derived from an antigen
      specific T-cell population would provide an accurate assessment of the overall
      response; however, this is time- and labor-intensive, preventing rapid and
      routine assessment of patient samples from clinical trials. By stimulating
      antigen-specific T cells that otherwise appear homogeneous on tetramer staining
      with graded amounts of cognate peptides, the authors show that individual cells
      downmodulate surface T-cell receptors (TCR) and thus lose tetramer reactivity
      with variable dynamics within the T-cell population. The dynamics of TCR
      downregulation represent an accurate assessment of an individual cell's antigen
      sensitivity, recognition efficiency, and relative functional state within an
      antigen-specific population and have direct correlation to killing capacity by
      chromium release as well as degranulation by CD107 mobilization. Furthermore,
      despite correlation of average T-cell function by all three techniques, TCR
      downregulation uncovered heterogeneity in T-cell responses after vaccination
      among patient samples directly ex vivo. When examined using this novel technique,
      antigen-specific T cells elicited by vaccination with heteroclitic peptides
      exhibited significantly different recognition efficiencies for the heteroclitic
      versus native peptides, translating into differences in functional responses.
      With advancing cancer vaccine trials, the capacity to detect and functionally
      characterize antigen-specific T-cell responses in detail is critical. Techniques,
      as presented here, that rapidly assess the overall antigen sensitivity,
      recognition efficiency, and functional status of patients' T-cell responses will
      guide future vaccine trials and immunotherapies.

PMID- 16000948
TI  - IL-12 production by human monocyte-derived dendritic cells: looking at the single
      cell.
AB  - Dendritic cells (DCs) are under investigation as immunotherapeutic agents in the
      treatment of cancer and infectious diseases. One of the important factors in
      skewing the immune response toward clinically beneficial TH1-type immunity is
      interleukin-12p70. IL-12p70 is synthesized and secreted in response to
      inflammatory cytokines, bacterial/viral components, and CD40 ligation. This study
      investigated the production of IL-12 by DCs at the single-cell level using a
      sensitive intracellular cytokine flow cytometry-based assay system. The authors
      observed that immature DCs could be stimulated with several compounds to produce
      IL-12, but that IL-12 production was a feature of a minority of activated DCs. IL
      12+ DCs were characterized as being partially matured (ie, absent or low CD83
      expression, with variable expression of CD1a and CD64). Interestingly, activated
      DCs lacked expression of the CD16 and CD64 Fc gammaR, which may have important
      implications for exogenous antigen-loading strategies.

PMID- 16000949
TI  - Expansion of alpha-galactosylceramide-stimulated Valpha24+ NKT cells cultured in
      the absence of animal materials.
AB  - Valpha24+ NKT is an innate lymphocyte with potential antitumor activity. Clinical
      applications of Valpha24+ natural killer (NK) T cells, which are innate
      lymphocytes with potential antitumor activity, require their in vitro expansion.
      To avoid the potential dangers posed to patients by fetal bovine serum (FBS), the
      authors evaluated non-FBS culture conditions for the selective and efficient
      expansion of human Valpha24+ NKT cells. Mononuclear cells (MNCs) and plasma from
      the peripheral blood of normal healthy donors were used before and after G-CSF
      mobilization. MNCs and plasma separated from apheresis products were also used.
      MNCs were cultured for 12 days in AIM-V medium containing alpha
      galactosylceramide (alpha-GalCer) (100 ng/mL) and IL-2 (100 U/mL) supplemented
      with FBS, autologous plasma, or autologous serum. The cultured cells were
      collected and their surface markers, intracellular cytokines, and cytotoxicity
      were evaluated. The highest expansion ratio for Valpha24+ NKT cells was obtained
      from G-CSF-mobilized MNCs cultured in medium containing 5% autologous plasma.
      Cultures containing MNCs and autologous plasma obtained before and after G-CSF
      mobilization had approximately 350-fold and 2,000-fold expansion ratios,
      respectively. These results suggest that G-CSF mobilization conferred a
      proliferative advantage to Valpha24+ NKT cells by modifying the biology of cells
      and plasma factors. Expanded Valpha24+ NKT cells retained their surface antigen
      expression and production of IFN-gamma and exhibited CD1d-independent
      cytotoxicity against tumor cells. Valpha24+ NKT cells can be efficiently expanded
      from G-CSF-mobilized peripheral blood MNCs in non-FBS culture conditions with
      alpha-GalCer and IL-2.

PMID- 16000950
TI  - Immunoselection of functional CMRF-56+ blood dendritic cells from multiple
      myeloma patients for immunotherapy.
AB  - Dendritic cells (DCs) loaded with tumor-associated antigens are a promising
      treatment to prevent disease relapse in patients with multiple myeloma (MM).
      Early-phase clinical trials have shown safety, efficacy, and immunologic
      responses in MM, but a key issue now is the isolation of a functional, clinically
      relevant DC preparation. The authors have described a unique blood DC (BDC)
      isolation platform based on positive immunoselection with the CMRF-56 antibody.
      To validate this as a feasible source of BDCs for immunotherapy, the authors
      undertook a quantitative and functional analysis of BDCs in MM patients and
      healthy donors. These data show that MM patients have similar numbers of
      CD11c+CD16+ and CD11c+CD16- BDCs but about half the number of CD11c-CD123+ BDCs
      in whole blood compared with healthy donors. BDCs could be isolated by CMRF-56+
      immunoselection from all MM patients tested, with similar yields and purity to
      healthy donors. These BDCs could be activated ex vivo with poly I:C or LPS.
      Furthermore, CMRF-56+ preparations could induce potent CD4+ and CD8+ T-lymphocyte
      responses in both MM patients and healthy donors. These data suggest that BDCs
      with in vitro functional integrity can be isolated from MM patients in sufficient
      numbers to justify a clinical trial.

PMID- 16000951
TI  - Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated
      cytotoxicity induced by tumor lysate-pulsed dendritic cells.
AB  - Dendritic cells (DCs) can induce cytotoxic T-cell (CTL) responses against tumor
      antigens in vitro and in vivo, yet few cancer patients experience tumor
      regression after DC-based vaccination. Combination with other treatment
      modalities, such as radiation or pharmacologic anticancer agents, may reduce
      tumor cell resistance against immune responses. The authors tested whether
      treatment with gemcitabine or cyclooxygenase-2 (COX-2) inhibitors increases the
      sensitivity of pancreatic carcinoma cells to CTL-mediated killing. Monocyte
      derived DCs of HLA-A2+ donors were loaded with lysate from the HLA-A2+ pancreatic
      carcinoma cell line Panc-1 and co-cultured with autologous CD3+ T cells. ELISPOT
      and cytotoxicity assays performed after two rounds of in vitro stimulation
      confirmed induction of a tumor-specific CTL response. Changes in the magnitude
      and the effector mechanism of the CTL response were analyzed after treatment of
      Panc-1 cells with gemcitabine and COX-2 inhibitors. Compared with gemcitabine,
      COX-2 inhibitors more effectively sensitized Panc-1 cells to CTL-mediated killing
      and showed less inhibition of T-cell activation by DCs in vitro. Using anti-CD95
      blocking antibody, the authors showed that the increase in CTL-mediated tumor
      cell killing observed after treatment with COX-2 inhibitors is dependent on
      CD95/CD95 ligand interaction. Increased apoptosis of Panc-1 cells treated with
      COX-2 inhibitor was also observed after incubation with agonistic anti-CD95
      antibody. Sensitization of cancer cells to CD95-dependent killing by CTLs
      represents a novel mechanism of action for COX-2 inhibitors and provides a
      rationale for their concomitant use with immunotherapeutic strategies such as DC
      based vaccination.

PMID- 16000952
TI  - The CXCR3 targeting chemokine CXCL11 has potent antitumor activity in vivo
      involving attraction of CD8+ T lymphocytes but not inhibition of angiogenesis.
AB  - The IFN-gamma-inducible and CXCR3-targeting human CXC chemokines CXCL9 (Mig) and
      CXCL10 (IP10) have potent antitumor activity through attraction of cytotoxic T
      lymphocytes and inhibition of angiogenesis. The more recently identified CXCR3
      targeting chemokine CXCL11 (I-TAC/IP9) proved to be a more potent chemokine than
      CXCL9 and CXCL10 in vitro, both in chemotaxis assays with CXCR3+ T lymphocytes
      and in calcium mobilization experiments. However, its antitumor activity in vivo
      has not been shown so far. To investigate this, mice were challenged with EL4 T
      cell lymphoma cells, genetically modified to produce murine CXCL11. Tumor growth
      curves showed complete rejection of CXCL11-producing tumors but not of control
      tumors. Tumor infiltrate analysis by flow cytometry showed a clear correlation
      between rejection of CXCL11-producing tumors and an increase of tumor
      infiltrating CD8+CXCR3+ as well as CD8+CXCR3- T lymphocytes. In vivo CD8 T-cell
      depletion completely abrogated the antitumor effect. No difference in
      angiogenesis between control and CXCL11-producing tumors was observed. In
      survivors, rechallenge experiments with wild-type tumor cells suggested
      development of protective antitumor immunity involving tumor-specific IFN-gamma
      production by CD8+ T lymphocytes. These experiments show, for the first time,
      antitumor activity of CXCL11 in vivo, which warrants exploration for its
      potential role in anticancer immunotherapy.

PMID- 16000953
TI  - Enhanced CD4+ T-cell response in DR4-transgenic mice to a hybrid peptide linking
      the Ii-Key segment of the invariant chain to the melanoma gp100(48-58) MHC class
      II epitope.
AB  - Linking the Ii-Key functional group LRMK, through a simple polymethylene linker,
      to the melanoma gp100(48-58) MHC class II epitope significantly enhances the
      vaccine response to that epitope in DR4-IE transgenic mice. A homologous series
      of Ii-Key/gp100(46-58) hybrids was synthesized to test the influence of spacer
      length (between Ii-Key and the gp100(48-58) epitope) on in vivo enhancement of
      gp100(48-58)-specific CD4+ T-lymphocyte responses. As measured by IFN-gamma and
      IL-4 ELISPOT cytokine assays, the most effective vaccine hybrid was the one with
      a shorter linker between Ii-Key and the epitope. Mechanistic reasons for this
      observation are considered. This structure-activity relationship was seen with
      bulk and CD4+ purified T cells, and both primary and secondary in vitro
      restimulation assays. CFA augmented the IFN-gamma response and to a lesser extent
      the IL-4 response. CpG enhanced a strong IFN-gamma response, with a negligible IL
      4 response. The 3- to 5-times enhancement of the total ELISPOT responses (number
      of spots x mean spot area) observed after vaccination with peptides consisting of
      an MHC class II epitope engineered into an Ii-Key hybrid indicates a potent
      vaccine effect. Such constructs can be applied to many diagnostic and therapeutic
      uses.

PMID- 16000955
TI  - Vaccination of cytotoxic T lymphocyte-directed peptides elicited and spread
      humoral and Th1-type immune responses to prostate-specific antigen protein in a
      prostate cancer patient.
AB  - The authors studied humoral and CD4+ T-cell responses in an HLA-A24+ prostate
      cancer patient vaccinated with cytotoxic T lymphocyte (CTL)-directed peptides,
      including a prostate-specific antigen (PSA)248-257 peptide, to understand what
      kinds of immune responses are elicited in peptide-vaccinated patients. The levels
      of immunoglobulin G (IgG) reactive to the administered PSA248-257 peptide or the
      PSA protein were kinetically examined. The level of IgG reactive to the PSA248
      257 peptide drastically increased after the peptide vaccination, with a peak
      after the seventh vaccination, whereas that of IgG reactive to the PSA protein
      continued to increase throughout the vaccination period. IgG reactive to the PSA
      protein after the 13th vaccination showed no reactivity to the administered PSA
      peptides. However, HLA-DRB1*1302-restricted and PSA protein-recognizing TH1-type
      CD4+ T-cell clone and line, with different specificity, were successfully
      established from the post-7th and post-13th peripheral blood mononuclear cells,
      respectively. Both CD4+ T cells produced interferon-gamma in response to
      naturally processed PSA secreted from prostate cancer cells, whereas their
      reactivity to the administered PSA248-257 peptide was undetectable or negligible.
      These findings indicate that vaccination with CTL-directed peptides, including a
      PSA-derived peptide, was able to elicit and spread humoral and TH1-type immune
      responses to the PSA protein.

PMID- 16000954
TI  - Intratumoral poly-N-acetyl glucosamine-based polymer matrix provokes a prolonged
      local inflammatory response that, when combined with IL-2, induces regression of
      malignant mesothelioma in a murine model.
AB  - The authors have previously shown that cytokines delivered directly into
      malignant mesothelioma (MM) tumors can retard tumor growth and mediate tumor
      regression under certain conditions. In this report the authors compared the
      efficacy of serial intratumoral injections of three cytokines, GM-CSF, IL-12, and
      IL-2, to their sustained release using a single injection in a poly-N-acetyl
      glucosamine gel. IL-2 combined with the polymer gel gave optimal antitumor
      results when MM tumors were accessible as either subcutaneous deposits or as
      masses spread throughout the peritoneal cavity. The gel acted not only as a slow
      release cytokine depot but also as a trigger for inflammation and recruited
      several immune cell types to the gel/tumor interface; when combined with IL-2
      (but not with GM-CSF or IL-12), it acted as a selective reservoir for
      infiltrating CD8+ T cells. Hence, the IL-2/gel may provide a microenvironment
      that allows intratumoral T cells to proliferate and retain their cytolytic
      functions as they encounter their cognate antigens expressed by tumor cells.

PMID- 16000956
TI  - Phase I trial of intravenous IL-4 pseudomonas exotoxin protein (NBI-3001) in
      patients with advanced solid tumors that express the IL-4 receptor.
AB  - NBI-3001 is a novel immunotoxin of attenuated Pseudomonas exotoxin fused to
      circularly permutated IL-4, which has shown some antitumor effects in
      glioblastoma multiforme with intratumoral administration. The authors evaluated
      the safety and tolerability of NBI-3001 administered intravenously in a dose
      escalation design to patients with renal cell and non-small cell lung carcinoma
      whose tumors showed at least 10% IL-4 receptor expression. Cohorts of three to
      six patients were treated at dose levels of 0.008, 0.016, and 0.027 mg/m2 daily x
      5 days every 28 days. Neutralizing antibody (NAB) titers, plasma levels of NBI
      3001, and patient tolerability were monitored sequentially. 14 patients received
      a total of 36 cycles of NBI-3001 (range 1-6). No dose-limiting toxicities were
      noted at dose levels 0.008 and 0.016 mg/m2. At 0.027 mg/m2, two patients
      developed self-limiting, grade 3 or 4 transaminase elevation during cycle 1. NAB
      titers of more than 1:100 were detected in five of the seven patients treated
      with at least two cycles; the median titer after cycle 1 and the median maximum
      titer in subsequent cycles were 1:50 and approximately 1:1,710, respectively. No
      objective tumor responses were noted. Eight of 12 evaluable patients with renal
      cell carcinoma had stable disease; four patients had disease progression. High
      NAB titers resulted in four patients being withdrawn from the study. The dose
      limiting toxicity for intravenous NBI-3001 was transaminase elevation at 0.027
      mg/m2. NBI-3001 at 0.016 mg/m2 was well tolerated. Low circulating levels of NBI
      3001, coupled with rising NAB titers, may have contributed to the lack of
      response in tumors that express IL-4R.

PMID- 16000957
TI  - Phase I study of a plasmid DNA vaccine encoding MART-1 in patients with resected
      melanoma at risk for relapse.
AB  - Immunization with plasmid DNA represents an attractive method for increasing
      cellular immune responses against cancer antigens. The safety and immunologic
      response of a plasmid encoding the MART-1 melanocyte differentiation antigen was
      evaluated in 12 patients with resected melanoma at risk for relapse. As a
      control, patients were also administered a plasmid encoding hepatitis B surface
      antigen (HBsAg). After establishing immunologic activity of the vaccines in mice,
      groups of three to six HLA-A2-positive patients were enrolled into one of three
      cohorts in which they received intramuscular injections of the MART-1 plasmid
      into the right deltoid and the HBsAg plasmid into the left deltoid at doses of
      0.1, 0.3, or 1.0 mg on days 1, 43, 85, and 127. Injections were well tolerated.
      Toxicity was limited to grade 1 pain and injection site tenderness. Systemic
      toxicity was not observed. Although baseline MART-1-specific lymphoproliferative
      and ELISPOT responses were evident, no patient manifested increases after
      injection of the MART-1 plasmid. Furthermore, changes in MART-1-specific
      precursors were not evident after immunization as assessed by an in vitro
      stimulation assay. No patients manifested a lymphoproliferative response to HBsAg
      antigen, and significant antibody responses to HBsAg were also not observed.
      Although injections were safe, the authors could not show significant immunologic
      responses to plasmid encoding MART-1 or HBsAg using the dose, schedule, and route
      of administration applied. This study underscores species differences in the
      ability to respond to plasmid immunogens.

PMID- 16000958
TI  - Immune monitoring in a phase 1 trial of a PSA DNA vaccine in patients with
      hormone-refractory prostate cancer.
AB  - Prostate cancer remains a leading cause of cancer illness and death among men in
      Europe. No curative treatment exists when the disease has spread beyond the
      prostate. Immunotherapy with DNA vaccines has emerged as a potential therapeutic
      approach for the induction of antitumor specific cytotoxic T lymphocytes. In this
      study six patients with hormone-refractory prostate cancer were monitored for
      their ability to mount PSA-specific cellular responses after receiving a pVAX/PSA
      DNA vaccine (patients 1-3, 100 microg; patients 7-9, 900 microg) with recombinant
      GM-CSF and IL-2 as adjuvants. IFNgamma ELISPOT showed that naturally processed
      PSA protein and PSA peptides are recognized by T cells in the blood of some
      prostate cancer patients after a PSA DNA vaccine. Analysis of other cytokines
      showed the production of IL-4 and IL-6 but importantly did not show an increase
      in the number of IL-10-producing cells after vaccination in any of the patients.
      The authors conclude that a pVAX/PSA DNA vaccine can induce PSA-specific cellular
      immune responses in patients with hormone-refractory prostate cancer, thus
      emphasizing the potential for PSA as a target molecule for the immunotherapy of
      prostate cancer.

PMID- 16000959
TI  - A novel flow cytometric assay for evaluating cell-mediated cytotoxicity.
AB  - Comprehensive evaluation of cell-mediated cytotoxicity is very important,
      especially in the clinical setting, when a surrogate immunologic endpoint that
      correlates with a clinical outcome needs to be defined. With the objective of
      simultaneously evaluating target cell death and effector cell frequency, the
      authors combined the measuring of the expression of the degranulation marker
      CD107a by effector cells with the apoptosis marker annexin V binding to target
      cells. Using human cytotoxic T lymphocytes, the authors found a significant
      incubation time-dependent increase of surface CD107a expression on effector cells
      due to degranulation. A parallel increase of annexin V binding to target cells
      due to target cell apoptosis was also found. These two parameters have shown
      excellent correlation in all effector/target cell systems studied. To find
      possible connections between effector cell degranulation (CD107a expression),
      granzyme B secretion, and target cell death (annexin V binding), the GrB ELISPOT
      assay and flow cytometric assay were performed and excellent cross-correlation
      was found between all three parameters. The specificity of the assay was also
      shown. These data show that this novel assay allows measurement of cytolytic cell
      activation and frequency as well as target cell death in the same sample.

PMID- 16000960
TI  - Large-scale depletion of CD25+ regulatory T cells from patient leukapheresis
      samples.
AB  - The ability to selectively enrich or deplete T lymphocytes of specific phenotype
      and function holds significant promise for application in adoptive immunotherapy
      protocols. Although CD4+ T cells can have an impact on CD8+ T-cell effector
      function, memory, and maintenance, a subset of CD4+ T cells, CD25+ regulatory T
      cells (Treg), can regulate peripheral self tolerance and possess the ability to
      suppress antitumor responses. The authors report the ability to selectively
      deplete CD25+ Treg cells from patient leukapheresis samples using a clinical
      grade, large-scale immunomagnetic system. Using leukapheresis samples containing
      up to 1.3 x 10(10) white blood cells, efficient depletion of Treg cells was
      measured by flow cytometric analysis of CD25 expression and FOXP3 expression on
      post-depletion products. Remnant CD25+ cells could not be detected in CD25
      depleted products after short-term culture in IL-2 or enriched following
      secondary immunomagnetic selection for CD25+ cells, confirming that efficient
      depletion had occurred. In parallel to efficient enrichment of CD25- cells,
      immunomagnetic selection resulted in the recovery of Treg cells, since CD25+
      lymphocytes removed during depletion were primarily composed of CD4+ T cells that
      expressed high levels of FOXP3 and possessed suppressive activity against
      autologous TCR-stimulated CD4+ CD25- T cells in vitro. These results show that
      selective separation of functional CD25+ Treg cells from large-scale samples can
      be performed in large scale under clinical-grade conditions with sufficient
      selection, recovery, viability, ability to expand, and function for potential use
      in adoptive immunotherapy.

PMID- 16000961
TI  - Autoimmune toxicities associated with the administration of antitumor vaccines
      and low-dose interleukin-2.
AB  - The purpose of this investigation was to evaluate the occurrence of autoimmune
      toxicities associated with the administration of low-dose IL-2 in conjunction
      with vaccines for melanoma. Ninety-three patients with stage IIB, III, or IV
      melanoma were enrolled in three clinical trials and received anti-melanoma
      vaccines on days 1, 8, 15, 29, 36, and 43. The vaccines comprised peptide-pulsed
      dendritic cells, autologous tumor cells with GM-CSF in Montanide ISA-51, or
      synthetic peptides with GM-CSF in Montanide ISA-51. In conjunction with the
      vaccines, all patients were administered 3 x 10(6) IU/m2/d IL-2 subcutaneously
      for 42 days, either days 8 to 49 or 29 to 70. Clinical and laboratory data from
      these studies were reviewed in aggregate to evaluate the occurrence of autoimmune
      toxicities. Of 91 evaluable patients, vitiligo was documented in 6 patients (7%).
      In addition, one patient experienced transient severe insulin-dependent diabetes
      that resolved after discontinuing IL-2, and another experienced an exacerbation
      of his pre-existing diabetes; these occurrences are consistent with an autoimmune
      insulitis. Four occurrences (4%) of transient minor ocular toxicity were
      documented, but no autoimmune ocular toxicities or changes in visual acuity were
      found. Of 55 evaluable patients, 14 experienced thyroid abnormalities (25%).
      These were attributed to an autoimmune thyroiditis, which was supported by
      findings of antithyroid antibodies in three of the seven patients evaluated.
      Overall, autoimmune toxicities affecting several organ systems were observed in
      patients receiving melanoma vaccines in conjunction with low-dose IL-2. None of
      these toxicities caused major long-term effects, though one was acutely life
      threatening and others contributed to treatment-related morbidity. Peptide- or
      cell-based vaccines administered in combination with low-dose IL-2 appear to be
      capable of breaking tolerance to self-antigens; despite the associated
      toxicities, these combinations may still be useful to administer as an
      immunotherapy for cancer. However, careful monitoring for autoimmune toxicities
      should be incorporated in future clinical studies incorporating low-dose IL-2.

PMID- 16000962
TI  - Ex vivo activated immune cells promote survival and stimulate multilineage
      hematopoietic recovery in myelosuppressed mice.
AB  - Recovery of multilineage hematopoiesis from severe myelosuppression due to
      chemotherapy and radiotherapy remains a clinical problem. The authors have
      developed a simple immunotherapy to treat this disease in a mouse model.
      Syngeneic spleen cells or xenogeneic human peripheral mononuclear cells were
      cultured ex vivo with a combination of IL-2 at 500 IU/mL, GM-CSF at 200 U/mL, and
      calcium ionophore A23187 at 100 ng/mL for 2 days and injected intravenously into
      mice that had previously received a lethal dose of carboplatin and radiation. The
      therapy was highly effective: a single injection of activated cells enhanced
      survival and simulated multilineage recovery of hematopoiesis. Ex vivo activated
      immune cells produced multiple cytokines, including several hematopoietic growth
      factors. Adherent cells were found to be more potent than nonadherent cells in
      promoting survival, and the therapy alone was capable of mobilizing peripheral
      blood stem cells in normal mice.

PMID- 16000963
TI  - Here's to heroes for nursing.

PMID- 16000964
TI  - Folic acid fortification: should oral contraceptives be next? PRO.

PMID- 16000965
TI  - Folic acid fortification: should oral contraceptives be next? CON.

PMID- 16000966
TI  - An intervention program for families with irritable infants.
AB  - PURPOSE: To describe and evaluate a home-based nursing intervention program, the
      REST routine, which incorporates the use of infant behavior assessment, pattern
      recognition, individualized infant schedules, specific management strategies, and
      parent education and support. STUDY DESIGN AND METHOD: A two-site clinical trial
      was conducted on 164 healthy full-term infants with excessive unexplained
      irritability or colic. Infants between the ages of 2 to 6 weeks were randomized
      to routine care or a home-based intervention program (n = 121). A third group (n
      = 43) of infants too old at entry for randomization (mean age = 10.4 weeks) were
      entered into a posttest-only group. RESULTS: Infants in the REST routine
      treatment group cried 1.3 hours per day on average following the intervention
      program as compared to the control group crying 3 hours per day (p = .02). Infant
      irritability was resolved (< 1 hour) in 62% of the treatment group while only in
      29% of the control group at the time of the 8-week follow-up visit (p = .04).
      CLINICAL IMPLICATIONS: Families in both the treatment and control groups reported
      benefiting from a nurse visiting in their home to inquire about their infant and
      their well-being. Options for individualizing the program for those most in need
      of intensive home visiting and other delivery modes for the intervention are
      areas for further investigation.

PMID- 16000967
TI  - Tailoring STI & HIV prevention programs for teens.
AB  - Successful HIV/sexually transmitted infection (STI) prevention programs are not
      "one size fits all." To effectively meet the HIV/STI prevention needs of all
      adolescents, programs should be developmentally and gender specific, should
      integrate an understanding of racial/ethnic culture, and should be open to
      variations in sexual expression. Nurse researchers have demonstrated the
      importance of these differences in programs, and this article offers concrete
      suggestions for ways to apply this knowledge in community programs.

PMID- 16000970
TI  - Family functioning and hope in children with juvenile rheumatoid arthritis.
AB  - PURPOSE: To examine the relationships among family functioning, hope, and quality
      of life in children with juvenile rheumatoid arthritis (JRA). STUDY DESIGN AND
      METHOD: Sixty-eight children (8 to 12 years of age) with a diagnosis of JRA and
      one of their parents/guardians participated in this descriptive correlational
      study. Parents completed the Feetham Family Functioning Survey (FFFS), the Parent
      Report for Children Pediatric Quality of Life Inventory (PedsQL), and the Parent
      Report for Children PedsQL Rheumatology Module. The children completed the
      Children's Hope Scale (CHS), the Child Report for PedsQL, and the Child Report
      PedsQL Rheumatology Module. Data were analyzed using chi-square, t-tests, and
      correlation analyses. RESULTS: Family functioning and children's hope showed a
      negative correlation, indicating that a child's hope was lower when the parent
      reported greater dissatisfaction with family functioning. Hope was not related to
      parent or child ratings of the child's quality of life. CLINICAL IMPLICATIONS: In
      caring for children with JRA, nurses can assess the family's satisfaction with
      relationships to the broader community, subsystems, and individual members and
      seek ways to promote healthy family functioning. Nurses also can assess the level
      of hope in children with JRA and facilitate the development of hopefulness by
      helping children establish goals and develop strategies to meet them.

PMID- 16000971
TI  - Lack of preparedness: experiences of first-time mothers.
AB  - PURPOSE: To examine the experiences of first-time mothers following discharge
      from the hospital after vaginal delivery. STUDY DESIGN AND METHOD: Qualitative,
      grounded theory. In-depth interviews were conducted with participants guided by
      open-ended semistructured questions. All interviews took place in the
      participants' homes within 4 weeks of delivery and were tape-recorded. Data
      collection and analysis occurred simultaneously. Open coding and selective coding
      were utilized to identify and refine concepts. Participants were primiparous,
      drawn from an urban location in the northeastern United States, English-speaking,
      and 18 to 35 years of age. RESULTS: Following the dramatic changes of pregnancy
      and delivery, the women in this study returned home feeling unprepared to care
      for themselves and their babies. Because of their lack of preparedness at a time
      of increased responsibility and vulnerability, they were overwhelmed. Exhausted,
      feeling unwell and isolated, they struggled to adapt to new role expectations.
      Propelled into information seeking by their lack of knowledge, they were further
      hampered by conflicting and fragmented advice. Family and friends were the
      primary sources for information for the majority of these new mothers, not
      healthcare professionals or services. CLINICAL IMPLICATIONS: Insight into the
      experiences of first-time mothers provides a framework for additional research
      and the development of programs and resources that will address their unique
      needs.

PMID- 16000972
TI  - Across the fertility lifespan: desire for pregnancy at conception.
AB  - PURPOSE: To illustrate trends in unintended pregnancy over a 5-year period and to
      describe variations in desire for pregnancy at conception in relation to maternal
      age, race/ethnicity, income, and education. STUDY DESIGN AND METHODS: Data were
      collected as part of the Iowa Barriers to Prenatal Care Project, a large,
      multiyear study of new mothers. A brief questionnaire eliciting maternal
      experiences and behaviors during pregnancy was administered to new mothers in all
      Iowa hospitals providing maternity care following the birth of their baby. Sample
      sizes ranged from 16,714 to 19,421 over the 5 years included in this analysis
      (1997 to 2001), and response rates ranged from 44% to 53%. RESULTS: The study
      sample closely matched the overall statewide profile of women in this age group.
      In each of the 5 years, about one third of the mothers giving birth indicated
      that they did not intend to become pregnant at that time, and another 4% to 5%
      indicated that they did not want to be pregnant at that time or in the future.
      There were no substantive variations across years. Maternal age, race/ethnicity,
      income, and education were significantly related to intendedness of pregnancy.
      CLINICAL IMPLICATIONS: The findings underscore the continuing challenge of
      unintended pregnancy, despite recent national attention to this issue. All women
      of childbearing age should be considered at risk for unintended pregnancy.
      Additional work is needed to examine reasons, attitudes, and behaviors associated
      with unintended pregnancies and to determine the relative predictive strength of
      key demographic variables to improve interventions aimed at decreasing unintended
      pregnancy rates.

PMID- 16000973
TI  - Early intervention for children and families: with special needs.
AB  - The purpose of this article is to provide a general overview of early
      intervention and how nurses can interface with this important program for
      children. "Early intervention" in this context refers to services for young
      children (birth to age 3) who have developmental delays or are at risk for
      delays, as well as for their families. These programs are administered by each
      state but are federally funded under Part C of the Individuals with Disabilities
      Act. The primary objective of early intervention is to maintain or maximize a
      child's development; a wide range of services may be provided including nursing,
      physical therapy, occupational therapy, and family counseling. Overall, early
      intervention programs have been shown to improve developmental outcomes,
      strengthen parent-child interactions, and provide a supportive family
      environment. There is a continued need for research, however, in many areas,
      including assessing the long-term effects of services for specific groups,
      determining the most effective means of providing services, and evaluating
      outcomes of family functioning.

PMID- 16000975
TI  - Water-soluble vitamins.

PMID- 16000983
TI  - Does practice make perfect? Not always.

PMID- 16000984
TI  - The CERRIE Report and its implications for nuclear medicine.

PMID- 16000985
TI  - Whole-body PET/CT: spectrum of physiological variants, artifacts and
      interpretative pitfalls in cancer patients.
AB  - Accurate diagnosis and staging in oncology is essential in the evaluation of
      cancer for optimal patient outcome. Conventional imaging techniques, such as
      computed tomography (CT), rely basically on morphological changes for tumour
      detection. Clinical experience, however, shows that morphological criteria may be
      misleading and may not always allow differentiation between benign and malignant
      lesions. Positron emission tomography (PET) with [F]fluorodeoxyglucose (FDG) is
      rapidly gaining a critical role in the clinical evaluation of patients with
      cancer. However, PET lacks anatomical landmarks for topographic orientation, and
      identification of abnormal glucose metabolic activity in regions close to organs
      with variable physiological FDG uptake can be difficult. To overcome these
      difficulties, a combined PET/CT scanner that acquires both functional (PET) and
      CT images has been recently developed. Proper interpretation of PET (and PET/CT)
      images requires a thorough understanding of the normal physiological distribution
      of FDG in the body, along with a knowledge of frequently encountered
      physiological variations in FDG distribution, and recognition of non-malignant
      causes of FDG uptake that can be confused with a malignant neoplasm. In addition,
      because of the utilization of the CT transmission information for the correction
      of the attenuation of the PET emission data (and for the reconstruction of the
      PET images), some artifacts may be generated. As a consequence, CT based
      attenuation correction of PET images may result in erroneous PET/CT
      interpretations. The aim of this extensively illustrated paper is to demonstrate
      several potential pitfalls encountered during the interpretation of PET/CT images
      so that radiologists can avoid false positive diagnoses and recognize inherently
      non-specific findings on PET/CT images obtained for oncological diagnosis.

PMID- 16000986
TI  - Potential pitfalls of 18F-FDG PET in a large series of patients treated for
      malignant lymphoma: prevalence and scan interpretation.
AB  - OBJECTIVE: To evaluate the prevalence and scan interpretation criteria useful in
      identifying non-tumoural F-FDG focal uptakes (potential pitfalls) in patients who
      had been previously treated for a malignant lymphoma studied by positron emission
      tomography (PET). MATERIALS: Nine hundred and ninety-six consecutive PET scans
      obtained in 706 patients with malignant lymphoma were reviewed. All patients had
      been previously treated by first-line chemo-radiotherapy, plus surgery when
      required, and were then studied by FDG PET to investigate suspected recurrence at
      doubtful or inconclusive conventional radiological imaging (ultrasound, computed
      tomography, magnetic resonance imaging). PET was obtained with patients in the
      fasted condition and after i.v. injection of 370 MBq of F-FDG; imaging was
      acquired 60-90 min later. In patients with focal FDG uptake the final diagnosis
      was reached on the basis of histological findings or long-term follow-up.
      RESULTS: Thirty-one of 134 PET scans (23.1%) showing focal FDG uptake were
      diagnosed as non-tumoural radiotracer uptake, related to the presence of brown
      fat in seven cases, thymic hyperplasia in five, muscles contraction in four,
      lymph node unspecific inflammation in four, mediastinal/pulmonary unspecific
      inflammation in four, gastritis in two, colitis in two, bacterial abscess in one,
      lactating breast in one, and herpes zoster in one. Each of the above cited
      situations has been reported in the literature, generally in the form of sporadic
      reports, as a potential cause of misinterpretation (false positive) in reading a
      PET scan with the potential for incorrect patient management. An accurate
      diagnosis in these patients was important for the following therapeutic decision
      making. CONCLUSIONS: In the whole series of patients with treated malignant
      lymphoma, the prevalence of non-tumoural FDG focal uptake during follow-up was
      relatively low (3.1%); conversely, it was relatively high when considering the
      sub-group of 'positive' PET only (23.1%). The importance of knowing these
      situations in order to avoid misinterpretation in reading PET scans needs to be
      emphasized. In this light, an accurate patient's history and a skilful nuclear
      medicine physician are very important factors. For the same purpose, it is
      reasonable to think that the use of hybrid PET/CT tomographs could also play an
      important role in helping to identify non-tumoural FDG focal uptake.

PMID- 16000987
TI  - Whole-body biodistribution, radiation dosimetry estimates for the PET
      norepinephrine transporter probe (S,S)-[18F]FMeNER-D2 in non-human primates.
AB  - BACKGROUND: (S,S)-[F]FMeNER-D2 is a recently developed norepinephrine transporter
      ligand which is a potentially useful radiotracer for mapping the brain and heart
      norepinephrine transporter in vivo using positron emission tomography. In this
      work, we quantified the biodistribution over time and radiation exposure to
      multiple organs with (S,S)-[F]FMeNER-D2. METHODS: Whole-body images were acquired
      for 21 time points in two cynomolgus monkeys for approximately 270 min after
      injection of radioligand. Compressed 3-D to 2-D planar images were used to
      identify organs with the highest radiation exposure at each time point. Estimates
      of the absorbed dose of radiation were calculated using the MIRDOSE 3.1 software
      program performed with the dynamic bladder and ICRP 30 gastrointestinal tract
      models. RESULTS: In planar images, peak values of the percent injected dose (%ID)
      at a time after radioligand injection were calculated for the lungs (26.76% ID at
      1.42 min), kidneys (13.55% ID at 2.18 min), whole brain (5.65% ID at 4.48 min),
      liver (7.20% ID at 2 min), red bone marrow (5.02% ID at 2.06 min), heart (2.36%
      ID at 1.42 min) and urinary bladder (23% ID at 250 min). Assuming a urine voiding
      interval of 2.4 h, the four organs with highest exposures in microGy . MBq ( mrad
      . mCi) were kidneys 126 (468), heart wall 108 (399), lungs 88.4 (327) and urinary
      bladder 114 (422). The effective doses were estimated with and without urine
      voiding at a range of 123 (33) and to 131 (35.5) microGy . MBq ( mrad . mCi).
      CONCLUSION: The estimated radiation burden of (S,S)-[F]FMeNER-D2 is comparable to
      that of other F radioligands.

PMID- 16000989
TI  - The feasibility of repeated left ventricular ejection fraction analysis with
      sequential single-dose radionuclide ventriculography.
AB  - OBJECTIVE: Repeated left ventricular ejection fraction (LVEF) analyses with
      sequential single-dose radionuclide ventriculography might be an interesting
      technique for monitoring the effect of positive inotropic interventions. The aim
      of the study was to assess the reproducibility of LVEF measurement with planar
      radionuclide ventriculography within 3 h, using a standard single dose of
      radioactive tracer. METHODS: Sixteen patients underwent routine planar
      radionuclide ventriculography with a standard dose of 500 MBq of
      [Tc]pertechnetate and returned after 3 h for a repeat planar radionuclide
      ventriculography without administration of additional tracer. RESULTS: The
      average initial LVEF was 35.1+/-18.6%-point (range, 12%-point to 68%-point). The
      mean difference of the LVEF between the initial planar radionuclide
      ventriculography and the repeat planar radionuclide ventriculography was 2.8%+/
      6.3% (range, -11.8% to 13.3%, P=NS). The correlation between both measurements
      was significant with a correlation coefficient of 0.995 (P<0.01). Bland-Altman
      analysis revealed a mean LVEF difference of 0.94%-point between the baseline
      planar radionuclide ventriculography and the repeat planar radionuclide
      ventriculography (95% confidence interval: -2.7%-point to 4.5%-point). The visual
      wall motion assessment showed excellent reproducibility, with a kappa-statistic
      of 0.98. CONCLUSION: Repeated radionuclide ventriculography with a 3 h interval
      using a single standard dose of 500 MBq of [Tc]pertechnetate is highly
      reproducible and will be useful for monitoring the effect of positive inotropic
      interventions.

PMID- 16000988
TI  - Assessment of left ventricular function and volumes for patients with dilated
      cardiomyopathy using gated myocardial perfusion SPECT and comparison with
      echocardiography.
AB  - AIM: Left ventricular function, volumes and regional wall motion provide valuable
      diagnostic information and are of long-term prognostic importance in patients
      with dilated cardiomyopathy (DCM). This study was designed to compare the
      effectiveness of two-dimensional echocardiography and gated single photon
      emission computed tomography (SPECT) to evaluate these parameters in patients
      with DCM. METHODS: Gated SPECT and two-dimensional echocardiography were
      performed in 45 patients with DCM, and in 10 normal subjects as the control
      group. Patients were divided into two groups according to the aetiology of DCM:
      group I, ischaemic DCM (n=30); group II, non-ischaemic DCM (n=15). All patients
      and the control group underwent resting myocardial gated SPECT, 45 min after
      injection of 555 MBq of Tc-methoxyisobutyl-isonitrile (Tc-MIBI). Gated SPECT
      data, including left ventricular volumes and left ventricular ejection fraction
      (LVEF), were processed using an automated algorithm. Simpson's method was used to
      evaluate these parameters. Regional wall motion was evaluated using both
      modalities and scored using a 16-segment model with a five-point scoring system.
      Perfusion defects were expressed as a percentage of the whole myocardium
      planimetered by a bull's-eye polar map of composite non-gated SPECT. Myocardial
      perfusion was scored using a 16-segment model with a four-point scoring system.
      RESULTS: Mean perfusion defects and perfusion defect scores were 25+/-13% and
      1.12+/-0.36 in group I and 4+/-8% and 0.76+/-0.26 in group II (P<0.01). The
      overall agreement between the two imaging modalities for the assessment of
      regional wall motion was 57% (403/720 segments: 269/480 segments in group I and
      134/240 segments in group II). With gated SPECT, LVEF was 27+/-9%, the end
      diastolic volume (EDV) was 212+/-71 ml and the end-systolic volume (ESV) was
      160+/-67 ml. With echocardiography, these values were 29+/-8%, 197+/-56 ml and
      139+/-47 ml, respectively. The correlation between gated SPECT and two
      dimensional echocardiography was good (r=0.72, P<0.01) for the assessment of
      LVEF. The correlation was also good for EDV and ESV, but with wider limits of
      agreement (r= 0.71, P<0.01 and r=0.71, P<0.01, respectively) and with
      significantly higher values with gated SPECT (P<0.01). For patients with a
      perfusion defect of <20% or low myocardial perfusion scores, a higher correlation
      was found between the two methods for the assessment of LVEF, EDV and ESV. On the
      other hand, the correlation was lower for the assessment of wall motion.
      CONCLUSIONS: Gated SPECT and two-dimensional echocardiography correlate well for
      the assessment of left ventricular function and volumes. Gated SPECT has the
      advantage of providing information about left ventricular function, dimensions
      and perfusion.

PMID- 16000990
TI  - Mediastinal intraoperative radioisotope sentinel lymph node mapping in non-small
      cell lung cancer.
AB  - BACKGROUND: Lymph node metastases are significant prognostic factors in localized
      non-small-cell lung cancer (NSCLC). Nodal micrometastases may not be detected
      using current histological methods. AIM: To determine the accuracy and role of
      sentinel lymph nodes (SLNs) in patients with NSCLC. METHODS: Intraoperative
      technetium-99m (Tc) sulphur colloid SLN mapping was performed in patients with
      NSCLC. Serial section histology and immunohistochemistry were used to validate
      the SLNs and to identify the presence of micrometastatic disease. The study was
      carried out on 28 consecutive patients (male/female, 25/3; mean age, 57.05+/-7.1
      years) with resectable NSCLC. During thoracotomy, 0.25 mCi of Tc sulphur colloid
      was injected into four quadrants peritumorally. Radioactivity was counted
      intraoperatively, a mean of 45 min (range, 30-60 min) after injection. SLN was
      defined as the node with the highest count rate using a hand-held gamma probe
      counter. Resection with mediastinal node dissection was performed and the
      findings were correlated with histological examination. RESULTS: SLNs were
      identified in 26 of 28 patients (92.8%) with a total number of 32 SLNs. Seven of
      32 (21.8%) of these SLNs were positive for metastatic involvement after
      histological and immunohistochemical examination. In two patients (7.1%), SLNs
      could not be found. CONCLUSIONS: These results demonstrate the feasibility of
      this procedure in identifying the first site of potential nodal metastasis of
      NSCLC. This method may improve the precision of pathological staging.

PMID- 16000991
TI  - Effects of radiation therapy on oesophageal transit in patients with inner
      quadrant breast tumour.
AB  - OBJECTIVES: The aim of this study was to evaluate quantitatively the effect of
      low doses of radiation therapy on the oesophageal transit in patients with inner
      quadrant breast carcinoma. METHODS: Eighteen female patients with locally
      advanced inner quadrant breast tumour were included in this study. A total dose
      of 5000 cGy in 25 fractions of 200 cGy was applied from four different treatment
      portals to all patients. Oesophageal motility was evaluated before and
      immediately after radiotherapy using oesophageal scintigraphy. The oesophageal
      transit times (ETTs) for the upper one-third, the lower two-thirds portion and
      the whole oesophagus were calculated. RESULTS: The upper one-third portion of the
      oesophagus received a mean dose of 600 cGy and the lower two-thirds portion
      received a mean dose of 1530 cGy as a result of 5000 cGy dose application. All of
      the patients developed grade 1 oesophageal toxicity. Post-radiation therapy ETT
      values were significantly higher compared to pre-radiation therapy ETT values
      (P<0.001). Before irradiation, ETT values for the upper one-third, distal two
      thirds of the oesophagus and the whole oesophagus were 4.77+/-1.08, 11.22+/-2.85
      and 11.61+/-2.97 s, respectively. After irradiation, ETT values for the upper one
      third, distal two-thirds of the oesophagus and the whole oesophagus were 6.92+/
      2.15, 23.30+/-5.65 and 23.74+/-5.70 s, respectively. CONCLUSIONS: Oesophageal
      transit seems to be affected by radiation even without a clinically significant
      oesophageal symptom and oesophageal scintigraphy allows sensitive, non-invasive
      and quantifiable assessment of the oesophageal transit time.

PMID- 16000992
TI  - Influence of dose rate on therapeutic success of radioiodine therapy of
      functional thyroid autonomy.
AB  - OBJECTIVE: To evaluate the effect of dose rate on the therapeutic success of
      radioiodine therapy (RIT) by retrospective analysis of two groups of patients
      with different dose rates during RIT. METHODS: The average dose rate until
      deposition of 50% of the total radiation dose achieved (the DL50 value) was
      calculated. Ninety patients with autonomy of the thyroid receiving radiation
      doses between 300 and 400 Gy were separated in groups with high DL50 values (the
      DL50 H group) and low DL50 values (the DL50L group). Before and 4 months after
      RIT free triiodothyronine (FT3), free thyroxine (FT4), basal thyroid stimulating
      hormone (TSHB), stimulated TSH (TSHS), thyroidal technetium uptake (TcTU), and
      the existence of focal abnormalities in thyroid scintigraphy were evaluated.
      RESULTS: The DL50 H and DL50L groups showed no differences before RIT in the
      parameters assessed as well as in total achieved dose and autonomous thyroid
      volume. After therapy a significant difference was found in TSHB with higher
      values in DL50 H (1.89+/-1.49 vs. 1.31+/-1.48 mU . l, P<0.05), FT4 showed a trend
      to lower values (13.8+/-4.0 vs. 16.1+/-6.2 pmol . l, P=0.09). CONCLUSION: The
      DL50 value has an influence on therapeutic success of RIT. This influence is only
      discrete and not likely to produce clinically relevant effects in the practical
      use of RIT.

PMID- 16000993
TI  - Thyroid stunning in vivo and in vitro.
AB  - AIM: To review published in-vivo and in-vitro quantitative dosimetric studies on
      thyroid stunning in order to derive novel data applicable in clinical practice.
      METHODS: A non-linear regression analysis was applied to describe the extent of
      thyroid stunning in thyroid remnants, as a function of the radiation absorbed
      dose of diagnostic radioiodine-131 (I), in thyroid cancer patients investigated
      in four in-vivo studies. The regression curves were fitted using individual
      patient absorbed doses or the mean absorbed doses for the groups of patients.
      Fitted curves were compared with two recent models, the first found in patients
      with benign thyroid disease and the second found in cultured thyroid cells after
      I irradiation. RESULTS: The extrapolated absorbed doses for the onset of thyroid
      stunning were 0 Gy delivered to thyroid cells in vitro, and < or =4 Gy and 34 Gy
      delivered to thyroid cells in vivo (malignant and benign conditions,
      respectively). Thyroid stunning amounted to roughly 50% in the case of 2 Gy
      delivered to thyroid cells in vitro, and in the case of < or =30 Gy and 472 Gy
      delivered to thyroid cells in vivo (malignant and benign conditions,
      respectively). CONCLUSIONS: There is no scintigraphically sufficient diagnostic
      amount of I that can be given prior to I therapy for thyroid cancer that does not
      cause thyroid stunning, i.e. it is not recommended to deliver pre-therapeutically
      more than a few gray (<5 Gy) into thyroid remnants. More investigations are
      required to confirm the proposed in-vitro and benign in-vivo models, but
      characteristic absorbed doses presented so far for in-vitro vs. in-vivo malignant
      vs. in-vivo benign thyroid environments differ roughly by an order of magnitude.

PMID- 16000994
TI  - Quality control of slope-intercept measurements of glomerular filtration rate
      using single-sample estimates.
AB  - OBJECTIVES: Measurement of glomerular filtration rate (GFR) using the slope
      intercept technique determines the plasma clearance curve by fitting a straight
      line to the logarithm of sample count rate. When two samples are used there is no
      check on the validity of curve fitting. GFR may also be estimated from single
      sample concentrations. This study describes a method of quality control for the
      two-sample technique using the agreement between the one-sample and two-sample
      estimates. METHODS: GFR measurements using Tc-DTPA were performed on 225 adults
      and 100 children using two samples taken between 2 h and 4 h post-injection. The
      two-sample values obtained using the British Nuclear Medicine Guidelines slope
      intercept technique were compared to one-sample estimates obtained using a new
      general equation. Equations describing the variation of GFR error with GFR value
      were defined. These were used to determine action levels giving the limits of
      expected agreement between slope-intercept and single-sample values. The use of
      these action levels for quality control was demonstrated in a further 120 GFR
      measurements. RESULTS: The variation of single-sample error estimate with GFR
      depended both on the time of sample and body surface area. For specific sample
      groups, the error variation with GFR could be approximated using a truncated
      quadratic equation. Four studies were identified as failing quality control in
      the dataset used to define the error equations. Two studies failed in the test
      dataset. CONCLUSIONS: One-sample equations give reliable estimates of GFR, which
      may be used for quality control of slope-intercept GFR assessment.

PMID- 16000995
TI  - A general equation for estimating glomerular filtration rate from a single plasma
      sample.
AB  - OBJECTIVES: Glomerular filtration rate (GFR) may be estimated from a single
      plasma sample measurement using empirical equations. This method forms the basis
      of international guidelines on GFR measurement. New guidelines have recently been
      recommended by the British Nuclear Medicine Society (BNMS). These use the slope
      intercept technique in which several samples are obtained. Quality control of
      measurement may be achieved by comparison with the individual single-sample
      values. This paper compares international guideline single-sample estimates of
      GFR with the new BNMS method and derives an improved general single-sample
      equation. METHODS: GFR measurements using Tc-DTPA were performed on 180 adults
      and 100 children using samples at approximately 2 h and 3 h and a further 45
      adults with samples at 2, 3 and 4 h. The two-sample values obtained using the
      BNMS guideline method were compared to one-sample estimates obtained using (1)
      international guidelines and (2) a new equation derived from the data. The new
      equation was evaluated in a further 145 subjects. RESULTS: The international
      guidelines technique had systematic differences between the one-sample and two
      sample estimates of GFR. The new equation had minimal systematic error and
      reduced random error (standard error of the estimate 4.5 ml . min per 1.73 m).
      CONCLUSIONS: There were significant differences between GFR values obtained using
      the international guidelines single-sample method and the slope-intercept method
      described in the BNMS guidelines. The new equation described in this paper gave
      considerably improved agreement and is recommended if single-sample estimates are
      to be used as quality control for BNMS guideline measurements.

PMID- 16000998
TI  - Choose the right nurse for the right job.

PMID- 16000996
TI  - Succinylated gelatine: an alternative to hydroxyethyl starch for labelling
      leukocytes with 99mTc-HMPAO.
AB  - BACKGROUND: Hydroxyethyl starch (HES) is the most used plasma expander in the
      sedimentation of the erythrocytes during the radiolabelling procedure for
      leukocytes in vitro. AIM: To evaluate the usefulness of succinylated gelatine
      (GEL), another colloidal plasma expander, as an alternative to HES in this
      process. METHODS: Two identical blood samples were obtained from 30 patients
      referred to white blood cell scintigraphy. The first sample was used to label
      leukocytes with Tc-HMPAO using the routine procedure, with HES. The other sample
      was used to label leukocytes with Tc-HMPAO using the same procedure, with GEL.
      The cell concentration of the leukocyte-platelet-rich plasma (LPRP) achieved
      after blood sedimentation was analysed. Labelling efficiency was calculated and
      the eosin Y viability and red cell/leukocyte ratio were evaluated from the final
      labelled cell suspension. RESULTS: Leukocytes and platelets recovered in LPRP
      were not statistically different between both HES and GEL samples (leukocytes:
      8.10x10/microl+/-3.82 and 7.80x10/microl+/-3.47; platelets: 411x10/microl+/-182
      and 406x10/microl+/-172, respectively). There were no significant differences
      between both agents on the labelling efficiency (HES: 80.3%+/-6.6%; GEL: 80.1%+/
      6.3%), the eosin Y viability (HES: 99.2%+/-1.3%; GEL: 99.3%+/-1.1%) and the red
      cell/leukocyte ratio (HES: 1.21+/-0.7; GEL: 0.9+/-0.5). CONCLUSION: These results
      show that succinylated gelatine can be used instead of hydroxyethyl starch in the
      labelling of leukocytes with Tc-HMPAO.

PMID- 16001000
TI  - Move from management to high-level leadership.
AB  - Hospital financial management and stellar leadership skills can help nurses reach
      executive status.

PMID- 16001001
TI  - "Soften" your environment to retain seasoned staff.
AB  - Help ease the nursing shortage by retaining senior nurses.

PMID- 16001002
TI  - Mitigate impediments to efficient patient flow.
AB  - Investigate and improve your facility's patient flow to meet updated JCAHO
      standards and improve patient care.

PMID- 16001003
TI  - Salary survey 2005.
AB  - Nursing Management's seventh annual salary survey offers nationwide data on nurse
      leaders' earnings and provides insight into compensation issues and retention
      incentives.

PMID- 16001004
TI  - A dynamic duo: staff development and you.
AB  - To meet the demands of an increasingly complex and aging patient population,
      implement a comprehensive framework for staff development.

PMID- 16001006
TI  - Keeping watch: California's staffing ratios.
AB  - Learn how the legislation of staffing ratios impacts nurse satisfaction and
      patient care.

PMID- 16001007
TI  - Best-practice protocols: implementing a rapid response system of care.
AB  - Rapid response teams provide a method for sending experts to the bedside to
      assist with patient evaluation and treatment before clinical deterioration
      progresses to cardiac arrest.

PMID- 16001008
TI  - The magnetic pull.
AB  - Aspirus Wausau Hospital and Saint Joseph's Hospital share the processes they used
      to fulfill the Forces of Magnetism.

PMID- 16001010
TI  - Improve outcomes with an insulin protocol.
AB  - Improve outcomes for diabetic patients undergoing cardiac surgery by following an
      insulin protocol.

PMID- 16001013
TI  - Tips for top challenges. Staff or team: What does it mean?

PMID- 16001014
TI  - State smoking restrictions for private-sector worksites, restaurants, and bars-
      United States, 1998 and 2004.
AB  - Secondhand smoke is a known carcinogen. Exposure to secondhand smoke causes
      approximately 35,000 heart disease deaths and 3,000 lung cancer deaths among
      nonsmokers in the United States every year. Implementing policies that establish
      smoke-free environments is the most effective approach to reducing secondhand
      smoke exposure among nonsmokers. Smoking restrictions and smoke-free policies can
      take the form of laws or regulations implemented at the state or local level or
      of voluntary policies implemented by private employers and businesses. Smoking
      restrictions limit smoking to certain areas within a venue; smoke-free policies
      ban smoking within the entire venue. One of the national health objectives for
      2010 is to establish laws in all 50 states and the District of Columbia (DC) that
      prohibit or restrict smoking in public places and worksites. A related objective
      calls for all worksites to voluntarily implement policies that prohibit or
      restrict smoking. To assess progress toward meeting the first objective, CDC
      reviewed the status of state laws restricting smoking as of December 31, 2004,
      updating a 1999 study that reported on such laws as of December 31, 1998. This
      report summarizes the changes in state smoking restrictions for private-sector
      worksites, restaurants, and bars that occurred during 1999-2004. The findings
      indicate an increase in the number and restrictiveness of state laws regulating
      smoking in private-sector worksites, restaurants, and bars from 1999 through
      2004. At the end of 2004, however, 16 states still had no restrictions on smoking
      in any of the three settings considered. Although secondhand smoke exposure among
      U.S. nonsmokers has decreased sharply in recent years, a substantial portion of
      nonsmokers continue to be exposed to secondhand smoke.

PMID- 16001015
TI  - Assessment of local health department smoking policies--North Carolina, July
      August 2003.
AB  - Secondhand smoke is a cause of disease in healthy nonsmokers, and an increasing
      number of states have adopted laws prohibiting smoking in private-sector
      worksites, restaurants, and bars. However, certain state governments have
      provisions in their state smoking restrictions that preempt more stringent local
      laws. North Carolina has such a preemptive state smoking law, passed in 1993,
      which mandates that 20% of the space within state-controlled buildings be
      designated as smoking areas. Exemptions from the law included local health
      departments (LHDs), providing an opportunity for public health practitioners to
      enact more stringent policies. To assess smoking policy gains from this
      exemption, a research team from the University of North Carolina at Chapel Hill
      (UNC) surveyed LHD directors. Results of the survey indicated uncertainty
      regarding the state law, with 37% of LHD directors believing they were prohibited
      from enacting a 100% tobacco-free policy on LHD grounds and 20% not knowing
      whether they were prohibited. The North Carolina Association of Local Health
      Directors used these findings to work with legislators in the North Carolina
      General Assembly to amend the state smoking law in 2005, specifying that the
      exemption applies to both LHD buildings and grounds.

PMID- 16001016
TI  - Progress toward poliomyelitis eradication--India, January 2004-May 2005.
AB  - Since 1988, the global incidence of polio has decreased by more than 99%, and
      three World Health Organization (WHO) regions (Americas, Western Pacific, and
      European) have been certified as polio-free . India, the largest of the six
      countries where polio remains endemic, experienced a large polio outbreak (1,600
      cases) in 2002. Since then, the Government of India (GOI) has accelerated its
      polio eradication activities by increasing the number and quality of
      supplementary immunization activities (SIAs), which reduced the number of
      reported cases to 225 in 2003, 134 in 2004, and 18 in 2005 (as of June 18).
      During 2004 and early 2005, taking advantage of the geographic restriction of
      wild poliovirus (WPV) circulation, GOI and its partners launched several
      immunization and surveillance strategies to maximize the probability of
      eliminating poliovirus transmission in India. With continued high-quality
      interventions, interruption of WPV transmission in India by the end of 2005
      appears feasible. This report summarizes progress toward polio elimination during
      January 2004-May 2005 toward that end.

PMID- 16001017
TI  - Ischemic preconditioning in the rat brain enhances the repair of endogenous
      oxidative DNA damage by activating the base-excision repair pathway.
AB  - The development of ischemic tolerance in the brain, whereby a brief period of
      sublethal 'preconditioning' ischemia attenuates injury from subsequent severe
      ischemia, may involve the activation of multiple intracellular signaling events
      that promote neuronal survival. In this study, the potential role of inducible
      DNA base-excision repair (BER), an endogenous adaptive response that prevents the
      detrimental effect of oxidative DNA damage, has been studied in the rat model of
      ischemic tolerance produced by three episodes of ischemic preconditioning (IP).
      This paradigm of IP, when applied 2 and 5 days before 2-h middle cerebral artery
      occlusion (MCAO), significantly decreased infarct volume in the frontal-parietal
      cortex 72 h later. Correlated with this protective effect, IP markedly attenuated
      the nuclear accumulations of several oxidative DNA lesions, including 8-oxodG, AP
      sites, and DNA strand breaks, after 2-h MCAO. Consequently, harmful DNA damage
      responsive events, including NAD depletion and p53 activation, were reduced
      during postischemic reperfusion in preconditioned brains. The mechanism
      underlying the decreased DNA damage in preconditioned brain was then investigated
      by measuring BER activities in nuclear extracts. Beta-polymerase-mediated BER
      activity was markedly increased after IP, and this activation occurred before (24
      h) and during the course of ischemic tolerance (48 to 72 h). In similar patterns,
      the activities for AP site and 8-oxodG incisions were also upregulated after IP.
      The upregulation of BER activities after IP was likely because of increased
      expression of repair enzymes beta-polymerase, AP endonuclease, and OGG1. These
      results suggest that the activation of the BER pathway may contribute to IP
      induced neuroprotection by enhancing the repair of endogenous oxidative DNA
      damage after ischemic injury.

PMID- 16001019
TI  - Climate of distrust.

PMID- 16001018
TI  - Global cerebral blood flow and metabolism during acute hyperketonemia in the
      awake and anesthetized rat.
AB  - In the human setting, it has been shown that acute increase in the concentration
      of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood
      flow (CBF) without affecting the overall cerebral metabolic activity. The
      mechanism by which this effect of ketone bodies was mediated is not known.
      Alterations in several parameters may possibly explain the increase in CBF and
      the resetting of the relation between CBF and cerebral metabolism. To study this
      phenomenon further, we measured global CBF and global cerebral metabolism with
      the Kety-Schmidt technique in the wakeful rat before and during infusion of
      ketone bodies. During acute hyperketonemia (average concentration of beta
      hydroxybutyrate: 6 mmol/L), global CBF increased 65% from 108 to 178 mL/100 g min
      and the cerebral metabolic rates for both oxygen and glucose remained constant.
      This resetting of the relation between CBF and cerebral metabolism could not be
      explained by alterations in blood pH or arterial CO2 tension. By measuring
      cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it
      could further be concluded that the brain pH was unchanged during acute
      hyperketonemia. These observations indicate that the mechanism responsible for
      the increase in CBF is rather a direct effect on the cerebral endothelium than
      via some metabolic interactions.

PMID- 16001020
TI  - Playing the name game.

PMID- 16001021
TI  - Rules of engagement.

PMID- 16001023
TI  - Flu officials pull back from raising global alert level.

PMID- 16001024
TI  - Climate change: is the US Congress bullying experts? Rajendra Pachauri
      interviewed by Quirin Schiermeier.

PMID- 16001025
TI  - Parasite infiltrates fruitfly research.

PMID- 16001026
TI  - Stem-cell 'heroes' celebrate a series of breakthroughs.

PMID- 16001027
TI  - Scientists finally get their hands on Kennewick man.

PMID- 16001029
TI  - US willing to pay for Russia's help in space.

PMID- 16001030
TI  - Genetic patent singles out Jewish women.

PMID- 16001032
TI  - Conservation biology: is this any way to save a species?

PMID- 16001033
TI  - Neuroscience: deep in thought.

PMID- 16001034
TI  - Electronic notebooks: a new leaf.

PMID- 16001035
TI  - Computer hardware: silicon down to the wire.

PMID- 16001039
TI  - Penalties plus high-quality review to fight plagiarism.

PMID- 16001040
TI  - Six-word rule could turn description into plagiarism.

PMID- 16001041
TI  - Plagiarism criteria ignore the way research evolves.

PMID- 16001042
TI  - Call for openness about farm-animal experiments.

PMID- 16001047
TI  - The mental Universe.

PMID- 16001048
TI  - Neuroscience: a home for the nicotine habit.

PMID- 16001049
TI  - Solid-state physics: doping the undopable.

PMID- 16001051
TI  - Conservation biology: where slugs may safely graze.

PMID- 16001050
TI  - Cancer biology: the weakest link?

PMID- 16001052
TI  - Nonlinear dynamics: when instability makes sense.

PMID- 16001055
TI  - Palaeoclimatology: the record for marine isotopic stage 11.
AB  - The marine isotopic stage 11 (MIS 11) is an extraordinarily long interglacial
      period in the Earth's history that occurred some 400,000 years ago and lasted for
      about 30,000 years. During this period there were weak, astronomically induced
      changes in the distribution of solar energy reaching the Earth. The conditions of
      this orbital climate forcing are similar to those of today's interglacial period,
      and they rendered the climate susceptible to other forcing--for example, to
      changes in the level of atmospheric carbon dioxide. Here we use ice-core data
      from the Antarctic Vostok core to reconstruct a complete atmospheric carbon
      dioxide record for MIS 11. The record indicates that values for carbon dioxide
      throughout the interglacial period were close to the Earth's pre-industrial
      levels and that both solar energy and carbon dioxide may have helped to make MIS
      11 exceptionally long. Anomalies in the oceanic carbonate system recorded in
      marine sediments at the time, for example while coral reefs were forming,
      apparently left no signature on atmospheric carbon dioxide concentrations.

PMID- 16001056
TI  - Acoustics: the vocal tract and the sound of a didgeridoo.
AB  - The Australian didgeridoo (or yidaki in the Yolngu language of northern
      Australia) is a simple musical instrument that, at the lips of an experienced
      player, is capable of a spectacular variety of timbres--considerably greater than
      those that can be coaxed from orchestral instruments, for example. To understand
      this phenomenon, we simultaneously measured the sound produced by the didgeridoo
      and the acoustic impedance of the player's vocal tract. We find that the maxima
      in the envelope of the sound spectrum are associated with minima in the impedance
      of the vocal tract, as measured just inside the lips. This acoustic effect is
      similar to the production of vowel sounds made during human speech or singing,
      although the mechanism is different, and leads to the surprising conclusion that
      experienced players are subconsciously using their glottis to accentuate the
      instrument's tonal variation.

PMID- 16001057
TI  - Mars: twin studies on Mars.

PMID- 16001058
TI  - Assessment of Mars Exploration Rover landing site predictions.
AB  - Comprehensive analyses of remote sensing data during the three-year effort to
      select the Mars Exploration Rover landing sites at Gusev crater and at Meridiani
      Planum correctly predicted the atmospheric density profile during entry and
      descent and the safe and trafficable surfaces explored by the two rovers. The
      Gusev crater site was correctly predicted to be a low-relief surface that was
      less rocky than the Viking landing sites but comparably dusty. A dark, low
      albedo, flat plain composed of basaltic sand and haematite with very few rocks
      was expected and found at Meridiani Planum. These results argue that future
      efforts to select safe landing sites based on existing and acquired remote
      sensing data will be successful. In contrast, geological interpretations of the
      sites based on remote sensing data were less certain and less successful, which
      emphasizes the inherent ambiguities in understanding surface geology from
      remotely sensed data and the uncertainty in predicting exactly what materials
      will be available for study at a landing site.

PMID- 16001060
TI  - Solar eclipses of Phobos and Deimos observed from the surface of Mars.
AB  - The small martian satellites Phobos and Deimos orbit in synchronous rotation with
      inclinations of only 0.01 degrees and 0.92 degrees , respectively, relative to
      the planet's equatorial plane. Thus, an observer at near-equatorial latitudes on
      Mars could occasionally observe solar eclipses by these satellites (see ref. 1,
      for example). Because the apparent angular diameter of the satellites is much
      smaller than that of the Sun, however, such events are more appropriately
      referred to as transits. Transit data can be used for correcting and refining the
      orbital ephemerides of the moons. For example, Phobos is known to exhibit a
      secular acceleration that is caused by tidal dissipation within Mars. Long-term,
      accurate measurements are needed to refine the magnitude and origin of this
      dissipation within the martian interior as well as to refine the predicted
      orbital evolution of both satellites. Here we present observations of six
      transits of Phobos and Deimos across the solar disk from cameras on Mars aboard
      the Mars Exploration Rovers Spirit and Opportunity. These are the first direct
      imaging observations of satellites transiting the Sun from the surface of another
      planet.

PMID- 16001059
TI  - An integrated view of the chemistry and mineralogy of martian soils.
AB  - The mineralogical and elemental compositions of the martian soil are indicators
      of chemical and physical weathering processes. Using data from the Mars
      Exploration Rovers, we show that bright dust deposits on opposite sides of the
      planet are part of a global unit and not dominated by the composition of local
      rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and
      could reflect either a global component or the general similarity in the
      compositions of the rocks from which they were derived. Increased levels of
      bromine are consistent with mobilization of soluble salts by thin films of liquid
      water, but the presence of olivine in analysed soil samples indicates that the
      extent of aqueous alteration of soils has been limited. Nickel abundances are
      enhanced at the immediate surface and indicate that the upper few millimetres of
      soil could contain up to one per cent meteoritic material.

PMID- 16001061
TI  - Aeolian processes at the Mars Exploration Rover Meridiani Planum landing site.
AB  - The martian surface is a natural laboratory for testing our understanding of the
      physics of aeolian (wind-related) processes in an environment different from that
      of Earth. Martian surface markings and atmospheric opacity are time-variable,
      indicating that fine particles at the surface are mobilized regularly by wind.
      Regolith (unconsolidated surface material) at the Mars Exploration Rover
      Opportunity's landing site has been affected greatly by wind, which has created
      and reoriented bedforms, sorted grains, and eroded bedrock. Aeolian features here
      preserve a unique record of changing wind direction and wind strength. Here we
      present an in situ examination of a martian bright wind streak, which provides
      evidence consistent with a previously proposed formational model for such
      features. We also show that a widely used criterion for distinguishing between
      aeolian saltation- and suspension-dominated grain behaviour is different on Mars,
      and that estimated wind friction speeds between 2 and 3 m s(-1), most recently
      from the northwest, are associated with recent global dust storms, providing
      ground truth for climate model predictions.

PMID- 16001062
TI  - Indication of drier periods on Mars from the chemistry and mineralogy of
      atmospheric dust.
AB  - The ubiquitous atmospheric dust on Mars is well mixed by periodic global dust
      storms, and such dust carries information about the environment in which it once
      formed and hence about the history of water on Mars. The Mars Exploration Rovers
      have permanent magnets to collect atmospheric dust for investigation by
      instruments on the rovers. Here we report results from Mossbauer spectroscopy and
      X-ray fluorescence of dust particles captured from the martian atmosphere by the
      magnets. The dust on the magnets contains magnetite and olivine; this indicates a
      basaltic origin of the dust and shows that magnetite, not maghemite, is the
      mineral mainly responsible for the magnetic properties of the dust. Furthermore,
      the dust on the magnets contains some ferric oxides, probably including
      nanocrystalline phases, so some alteration or oxidation of the basaltic dust
      seems to have occurred. The presence of olivine indicates that liquid water did
      not play a dominant role in the processes that formed the atmospheric dust.

PMID- 16001063
TI  - Water alteration of rocks and soils on Mars at the Spirit rover site in Gusev
      crater.
AB  - Gusev crater was selected as the landing site for the Spirit rover because of the
      possibility that it once held a lake. Thus one of the rover's tasks was to search
      for evidence of lake sediments. However, the plains at the landing site were
      found to be covered by a regolith composed of olivine-rich basaltic rock and
      windblown 'global' dust. The analyses of three rock interiors exposed by the rock
      abrasion tool showed that they are similar to one another, consistent with having
      originated from a common lava flow. Here we report the investigation of soils,
      rock coatings and rock interiors by the Spirit rover from sol (martian day) 1 to
      sol 156, from its landing site to the base of the Columbia hills. The physical
      and chemical characteristics of the materials analysed provide evidence for
      limited but unequivocal interaction between water and the volcanic rocks of the
      Gusev plains. This evidence includes the softness of rock interiors that contain
      anomalously high concentrations of sulphur, chlorine and bromine relative to
      terrestrial basalts and martian meteorites; sulphur, chlorine and ferric iron
      enrichments in multilayer coatings on the light-toned rock Mazatzal; high bromine
      concentration in filled vugs and veins within the plains basalts; positive
      correlations between magnesium, sulphur and other salt components in trench
      soils; and decoupling of sulphur, chlorine and bromine concentrations in trench
      soils compared to Gusev surface soils, indicating chemical mobility and
      separation.

PMID- 16001064
TI  - Dynamic predictive coding by the retina.
AB  - Retinal ganglion cells convey the visual image from the eye to the brain. They
      generally encode local differences in space and changes in time rather than the
      raw image intensity. This can be seen as a strategy of predictive coding, adapted
      through evolution to the average image statistics of the natural environment. Yet
      animals encounter many environments with visual statistics different from the
      average scene. Here we show that when this happens, the retina adjusts its
      processing dynamically. The spatio-temporal receptive fields of retinal ganglion
      cells change after a few seconds in a new environment. The changes are adaptive,
      in that the new receptive field improves predictive coding under the new image
      statistics. We show that a network model with plastic synapses can account for
      the large variety of observed adaptations.

PMID- 16001065
TI  - Photon blockade in an optical cavity with one trapped atom.
AB  - At low temperatures, sufficiently small metallic and semiconductor devices
      exhibit the 'Coulomb blockade' effect, in which charge transport through the
      device occurs on an electron-by-electron basis. For example, a single electron on
      a metallic island can block the flow of another electron if the charging energy
      of the island greatly exceeds the thermal energy. The analogous effect of 'photon
      blockade' has been proposed for the transport of light through an optical system;
      this involves photon-photon interactions in a nonlinear optical cavity. Here we
      report observations of photon blockade for the light transmitted by an optical
      cavity containing one trapped atom, in the regime of strong atom-cavity coupling.
      Excitation of the atom-cavity system by a first photon blocks the transmission of
      a second photon, thereby converting an incident poissonian stream of photons into
      a sub-poissonian, anti-bunched stream. This is confirmed by measurements of the
      photon statistics of the transmitted field. Our observations of photon blockade
      represent an advance over traditional nonlinear optics and laser physics, into a
      regime with dynamical processes involving atoms and photons taken one-by-one.

PMID- 16001066
TI  - Doping semiconductor nanocrystals.
AB  - Doping--the intentional introduction of impurities into a material--is
      fundamental to controlling the properties of bulk semiconductors. This has
      stimulated similar efforts to dope semiconductor nanocrystals. Despite some
      successes, many of these efforts have failed, for reasons that remain unclear.
      For example, Mn can be incorporated into nanocrystals of CdS and ZnSe (refs 7-9),
      but not into CdSe (ref. 12)--despite comparable bulk solubilities of near 50 per
      cent. These difficulties, which have hindered development of new nanocrystalline
      materials, are often attributed to 'self-purification', an allegedly intrinsic
      mechanism whereby impurities are expelled. Here we show instead that the
      underlying mechanism that controls doping is the initial adsorption of impurities
      on the nanocrystal surface during growth. We find that adsorption--and therefore
      doping efficiency--is determined by three main factors: surface morphology,
      nanocrystal shape, and surfactants in the growth solution. Calculated Mn
      adsorption energies and equilibrium shapes for several nanocrystals lead to
      specific doping predictions. These are confirmed by measuring how the Mn
      concentration in ZnSe varies with nanocrystal size and shape. Finally, we use our
      predictions to incorporate Mn into previously undopable CdSe nanocrystals. This
      success establishes that earlier difficulties with doping are not intrinsic, and
      suggests that a variety of doped nanocrystals--for applications from solar cells
      to spintronics--can be anticipated.

PMID- 16001067
TI  - Breaking of Henry's law for noble gas and CO2 solubility in silicate melt under
      pressure.
AB  - Degassing of the Earth is still poorly understood, as is the large scatter in
      He/Ar ratios observed in mid-ocean ridge basalts. A possible explanation for such
      observations is that vesiculation occurs at great depths with noble-gas
      solubilities different from those measured at 1 bar (ref. 1). Here we develop a
      hard-sphere model for noble-gas solubility and find that, owing to melt
      compaction, solubility may decrease by several orders of magnitude when pressure
      increases, an effect subtly overbalanced by the compression of the fluid phase.
      Our results satisfactorily explain recent experimental data on argon solubility
      in silicate melts, where argon concentration increases almost linearly with
      pressure, then levels off at pressures of 50-100 kbar (refs 2-5). We also model
      vesiculation during magma ascent at ridges and find that noble-gas partitioning
      between melt and CO2 vesicles at depth differs significantly from that at low
      pressure. Starting at 10 kbar (approximately 35 km depth), several stages of
      vesiculation occur followed by vesicle loss, which explains the broad variability
      of He-Ar concentration data in mid-ocean ridge basalts. 'Popping rocks',
      exceptional samples with high vesicularity, may represent fully vesiculated ridge
      magma, whereas common samples would simply have lost such vesicles.

PMID- 16001068
TI  - Generation time and temporal scaling of bird population dynamics.
AB  - Theoretical studies have shown that variation in density regulation strongly
      influences population dynamics, yet our understanding of factors influencing the
      strength of density dependence in natural populations still is limited.
      Consequently, few general hypotheses have been advanced to explain the large
      differences between species in the magnitude of population fluctuations. One
      reason for this is that the detection of density regulation in population time
      series is complicated by time lags induced by the life history of species that
      make it difficult to separate the relative contributions of intrinsic and
      extrinsic factors to the population dynamics. Here we use population time series
      for 23 bird species to estimate parameters of a stochastic density-dependent age
      structured model. We show that both the strength of total density dependence in
      the life history and the magnitude of environmental stochasticity, including
      transient fluctuations in age structure, increase with generation time. These
      results indicate that the relationships between demographic and life-history
      traits in birds translate into distinct population dynamical patterns that are
      apparent only on a scale of generations.

PMID- 16001069
TI  - Nicotine reinforcement and cognition restored by targeted expression of nicotinic
      receptors.
AB  - Worldwide, 100 million people are expected to die this century from the
      consequences of nicotine addiction, but nicotine is also known to enhance
      cognitive performance. Identifying the molecular mechanisms involved in nicotine
      reinforcement and cognition is a priority and requires the development of new in
      vivo experimental paradigms. The ventral tegmental area (VTA) of the midbrain is
      thought to mediate the reinforcement properties of many drugs of abuse. Here we
      specifically re-expressed the beta2-subunit of the nicotinic acetylcholine
      receptor (nAChR) by stereotaxically injecting a lentiviral vector into the VTA of
      mice carrying beta2-subunit deletions. We demonstrate the efficient re-expression
      of electrophysiologically responsive, ligand-binding nicotinic acetylcholine
      receptors in dopamine-containing neurons of the VTA, together with the recovery
      of nicotine-elicited dopamine release and nicotine self-administration. We also
      quantified exploratory behaviours of the mice, and showed that beta2-subunit re
      expression restored slow exploratory behaviour (a measure of cognitive function)
      to wild-type levels, but did not affect fast navigation behaviour. We thus
      demonstrate the sufficient role of the VTA in both nicotine reinforcement and
      endogenous cholinergic regulation of cognitive functions.

PMID- 16001070
TI  - ATP is a mediator of chemosensory transduction in the central nervous system.
AB  - Extracellular signalling by the purine nucleotide ATP has long been associated
      with sensory function. In the periphery, ATP mediates nociception,
      mechanosensitivity, thermal sensitivity and O2 chemosensitivity. These processes
      share a common mechanism that involves the release of ATP to excite afferent
      fibres via activation of ionotropic P2X and/or metabotropic P2Y receptors.
      Chemosensors located in the brainstem are crucial for the maintenance of
      physiological levels of blood gases through the regulation of breathing. Here we
      show that an increase in pCO2 in the arterial blood triggers the immediate
      release of ATP from three chemosensitive regions located on the ventral surface
      of the medulla oblongata. Blockade of ATP receptors at these sites diminishes the
      chemosensory control of breathing, suggesting that ATP release constitutes a key
      step in central chemosensory transduction. These new data suggest that ATP, a
      phylogenetically ancient, unique and simple molecule, has been widely used in the
      evolution of afferent systems to mediate distinct forms of sensory transduction
      not only in the periphery but also within the central nervous system.

PMID- 16001071
TI  - Angiotensin-converting enzyme 2 protects from severe acute lung failure.
AB  - Acute respiratory distress syndrome (ARDS), the most severe form of acute lung
      injury, is a devastating clinical syndrome with a high mortality rate (30-60%)
      (refs 1-3). Predisposing factors for ARDS are diverse and include sepsis,
      aspiration, pneumonias and infections with the severe acute respiratory syndrome
      (SARS) coronavirus. At present, there are no effective drugs for improving the
      clinical outcome of ARDS. Angiotensin-converting enzyme (ACE) and ACE2 are
      homologues with different key functions in the renin-angiotensin system. ACE
      cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates
      angiotensin II and is a negative regulator of the system. ACE2 has also recently
      been identified as a potential SARS virus receptor and is expressed in lungs.
      Here we report that ACE2 and the angiotensin II type 2 receptor (AT2) protect
      mice from severe acute lung injury induced by acid aspiration or sepsis. However,
      other components of the renin-angiotensin system, including ACE, angiotensin II
      and the angiotensin II type 1a receptor (AT1a), promote disease pathogenesis,
      induce lung oedemas and impair lung function. We show that mice deficient for Ace
      show markedly improved disease, and also that recombinant ACE2 can protect mice
      from severe acute lung injury. Our data identify a critical function for ACE2 in
      acute lung injury, pointing to a possible therapy for a syndrome affecting
      millions of people worldwide every year.

PMID- 16001072
TI  - Integrative genomic analyses identify MITF as a lineage survival oncogene
      amplified in malignant melanoma.
AB  - Systematic analyses of cancer genomes promise to unveil patterns of genetic
      alterations linked to the genesis and spread of human cancers. High-density
      single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide
      identification of both loss-of-heterozygosity events and copy-number alterations
      in cancer. Here, by integrating SNP array-based genetic maps with gene expression
      signatures derived from NCI60 cell lines, we identified the melanocyte master
      regulator MITF (microphthalmia-associated transcription factor) as the target of
      a novel melanoma amplification. We found that MITF amplification was more
      prevalent in metastatic disease and correlated with decreased overall patient
      survival. BRAF mutation and p16 inactivation accompanied MITF amplification in
      melanoma cell lines. Ectopic MITF expression in conjunction with the BRAF(V600E)
      mutant transformed primary human melanocytes, and thus MITF can function as a
      melanoma oncogene. Reduction of MITF activity sensitizes melanoma cells to
      chemotherapeutic agents. Targeting MITF in combination with BRAF or cyclin
      dependent kinase inhibitors may offer a rational therapeutic avenue into
      melanoma, a highly chemotherapy-resistant neoplasm. Together, these data suggest
      that MITF represents a distinct class of 'lineage survival' or 'lineage
      addiction' oncogenes required for both tissue-specific cancer development and
      tumour progression.

PMID- 16001074
TI  - Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae.
AB  - A functional genomics approach has revealed that caveolae/raft-mediated
      endocytosis is subject to regulation by a large number of kinases. Here we
      explore the role of some of these kinases in caveolae dynamics. We discover that
      caveolae operate using principles different from classical membrane trafficking.
      First, each caveolar coat contains a set number (one 'quantum') of caveolin-1
      molecules. Second, caveolae are either stored as in stationary multi-caveolar
      structures at the plasma membrane, or undergo continuous cycles of fission and
      fusion with the plasma membrane in a small volume beneath the surface, without
      disassembling the caveolar coat. Third, a switch mechanism shifts caveolae from
      this localized cycle to long-range cytoplasmic transport. We have identified six
      kinases that regulate different steps of the caveolar cycle. Our observations
      reveal new principles in caveolae trafficking and suggest that the dynamic
      properties of caveolae and their transport competence are regulated by different
      kinases operating at several levels.

PMID- 16001073
TI  - Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic
      instability.
AB  - The tumour microenvironment can be a potent carcinogen, not only by facilitating
      cancer progression and activating dormant cancer cells, but also by stimulating
      tumour formation. We have previously investigated stromelysin-1/matrix
      metalloproteinase-3 (MMP-3), a stromal enzyme upregulated in many breast tumours,
      and found that MMP-3 can cause epithelial-mesenchymal transition (EMT) and
      malignant transformation in cultured cells, and genomically unstable mammary
      carcinomas in transgenic mice. Here we explain the molecular pathways by which
      MMP-3 exerts these effects: exposure of mouse mammary epithelial cells to MMP-3
      induces the expression of an alternatively spliced form of Rac1, which causes an
      increase in cellular reactive oxygen species (ROS). The ROS stimulate the
      expression of the transcription factor Snail and EMT, and cause oxidative damage
      to DNA and genomic instability. These findings identify a previously undescribed
      pathway in which a component of the breast tumour microenvironment alters
      cellular structure in culture and tissue structure in vivo, leading to malignant
      transformation.

PMID- 16001075
TI  - Molecular basis of photoprotection and control of photosynthetic light
      harvesting.
AB  - In order to maximize their use of light energy in photosynthesis, plants have
      molecules that act as light-harvesting antennae, which collect light quanta and
      deliver them to the reaction centres, where energy conversion into a chemical
      form takes place. The functioning of the antenna responds to the extreme changes
      in the intensity of sunlight encountered in nature. In shade, light is
      efficiently harvested in photosynthesis. However, in full sunlight, much of the
      energy absorbed is not needed and there are vitally important switches to
      specific antenna states, which safely dissipate the excess energy as heat. This
      is essential for plant survival, because it provides protection against the
      potential photo-damage of the photosynthetic membrane. But whereas the features
      that establish high photosynthetic efficiency have been highlighted, almost
      nothing is known about the molecular nature of the dissipative states. Recently,
      the atomic structure of the major plant light-harvesting antenna protein, LHCII,
      has been determined by X-ray crystallography. Here we demonstrate that this is
      the structure of a dissipative state of LHCII. We present a spectroscopic
      analysis of this crystal form, and identify the specific changes in configuration
      of its pigment population that give LHCII the intrinsic capability to regulate
      energy flow. This provides a molecular basis for understanding the control of
      photosynthetic light-harvesting.

PMID- 16001076
TI  - X-ray structure of a tetranucleosome and its implications for the chromatin
      fibre.
AB  - DNA in eukaryotic chromosomes is organized in arrays of nucleosomes compacted
      into chromatin fibres. This higher-order structure of nucleosomes is the
      substrate for DNA replication, recombination, transcription and repair. Although
      the structure of the nucleosome core is known at near-atomic resolution, even the
      most fundamental information about the organization of nucleosomes in the fibre
      is controversial. Here we report the crystal structure of an oligonucleosome (a
      compact tetranucleosome) at 9 A resolution, solved by molecular replacement using
      the nucleosome core structure. The structure shows that linker DNA zigzags back
      and forth between two stacks of nucleosome cores, which form a truncated two
      start helix, and does not follow a path compatible with a one-start solenoidal
      helix. The length of linker DNA is most probably buffered by stretching of the
      DNA contained in the nucleosome cores. We have built continuous fibre models by
      successively stacking tetranucleosomes one on another. The resulting models are
      nearly fully compacted and most closely resemble the previously described crossed
      linker model. They suggest that the interfaces between nucleosomes along a single
      helix start are polymorphic.

PMID- 16001078
TI  - Spatial and temporal coordination of expression of immune response genes during
      Pseudomonas infection of horseshoe crab, Carcinoscorpius rotundicauda.
AB  - Knowledge on how genes are turned on/off during infection and immunity is
      lacking. Here, we report the co-regulation of diverse clusters of functionally
      related immune response genes in a horseshoe crab, Carcinoscorpius rotundicauda.
      Expressed sequence tag (EST) clusters for frontline immune defense, cell
      signalling, apoptosis and stress response genes were expressed or repressed
      spatio-temporally during the acute phase of Pseudomonas infection. An infection
      time course monitored by virtual Northern evaluation indicates upregulation of
      genes in blood cells (amebocytes) at 3-h postinfection, whereas most of the
      hepatopancreas genes remained down regulated over 72 h of infection. Thus, the
      two tissues orchestrate a coordinated and timely response to infection. The
      hepatopancreas probably immuno-modulates the expression of other genes and serves
      as a reservoir for later response, if/when chronic infection ensues. On the other
      hand, being the first to encounter pathogens, we reasoned that amebocytes would
      respond acutely to infection. Besides acute transactivation of the immune genes,
      the amebocytes maintained morphological integrity, indicating their ability to
      synthesise and store/secrete the immune proteins and effectors to sustain the
      frontline innate immune defense, while simultaneously elicit complement-mediated
      phagocytosis of the invading pathogen. Our results show that the immune response
      against Pseudomonas infection is spatially and temporally coordinated.

PMID- 16001079
TI  - Phosphorylation of CFTR by PKA promotes binding of the regulatory domain.
AB  - The unphosphorylated regulatory (R) domain of the Cystic Fibrosis Transmembrane
      conductance Regulator (CFTR) is often viewed as an inhibitor that is released by
      phosphorylation. To test this notion, we studied domain interactions using CFTR
      channels assembled from three polypeptides. Nucleotides encoding the R domain (aa
      635-836) were replaced with an internal ribosome entry sequence so that amino-
      and carboxyl-terminal half-molecules would be translated from the same mRNA
      transcript. Although only core glycosylation was detected on SplitDeltaR,
      biotinylation, immunostaining, and functional studies clearly demonstrated its
      trafficking to the plasma membrane. SplitDeltaR generated a constitutive halide
      permeability, which became responsive to cAMP when the missing R domain was
      coexpressed. Each half-molecule was co-precipitated by antibody against the other
      half. Contrary to expectations, GST-R domain was pulled down only if
      prephosphorylated by protein kinase A, and coexpressed R domain was precipitated
      with SplitDeltaR much more efficiently when cells were stimulated with cAMP.
      These results indicate that phosphorylation regulates CFTR by promoting
      association of the R domain with other domains rather than by causing its
      dissociation from an inhibitory site.

PMID- 16001081
TI  - HnRNP L represses exon splicing via a regulated exonic splicing silencer.
AB  - Skipping of mammalian exons during pre-mRNA splicing is commonly mediated by the
      activity of exonic splicing silencers (ESSs). We have recently identified a
      regulated ESS within variable exon 4 of the CD45 gene, named ESS1, that is
      necessary and sufficient for partial exon repression in resting T cells and has
      additional silencing activity upon T-cell activation. In this study, we identify
      three heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind specifically to
      ESS1. The binding of one of these proteins, hnRNP-L, is significantly decreased
      by mutations that disrupt both the basal and induced activities of ESS1.
      Recombinant hnRNP-L functions to repress exon inclusion in vitro in an ESS1
      dependent manner. Moreover, depletion of hnRNP-L, either in vitro or in vivo,
      leads to increased exon inclusion. In contrast, the other ESS1-binding proteins,
      PTB and hnRNP E2, do not discriminate between wild-type and mutant ESS1 in
      binding studies, and do not specifically alter ESS1-dependent splicing in vitro.
      Together, these studies demonstrate that hnRNP-L is the primary protein through
      which CD45 exon 4 silencing is mediated by the regulatory sequence ESS1.

PMID- 16001080
TI  - AIF suppresses chemical stress-induced apoptosis and maintains the transformed
      state of tumor cells.
AB  - Apoptosis-inducing factor (AIF) exhibits reactive oxygen species (ROS)-generating
      NADH oxidase activity of unknown significance, which is dispensable for
      apoptosis. We knocked out the aif gene in two human colon carcinoma cell lines
      that displayed lower mitochondrial complex I oxidoreductase activity and produced
      less ROS, but showed increased sensitivity to peroxide- or drug-induced
      apoptosis. AIF knockout cells failed to form tumors in athymic mice or grow in
      soft agar. Only AIF with intact NADH oxidase activity restored complex I activity
      and anchorage-independent growth of aif knockout cells, and induced aif
      transfected mouse NIH3T3 cells to form foci. AIF knockdown in different carcinoma
      cell types resulted in lower superoxide levels, enhanced apoptosis sensitivity
      and loss of tumorigenicity. Antioxidants sensitized AIF-expressing cells to
      apoptosis, but had no effect on tumorigenicity. In summary, AIF-mediated
      resistance to chemical stress involves ROS and probably also mitochondrial
      complex I. AIF maintains the transformed state of colon cancer cells through its
      NADH oxidase activity, by mechanisms that involve complex I function. On both
      counts, AIF represents a novel type of cancer drug target.

PMID- 16001082
TI  - Ca2+ spikes in the flagellum control chemotactic behavior of sperm.
AB  - The events that occur during chemotaxis of sperm are only partly known. As an
      essential step toward determining the underlying mechanism, we have recorded Ca2+
      dynamics in swimming sperm of marine invertebrates. Stimulation of the sea urchin
      Arbacia punctulata by the chemoattractant or by intracellular cGMP evokes Ca2+
      spikes in the flagellum. A Ca2+ spike elicits a turn in the trajectory followed
      by a period of straight swimming ('turn-and-run'). The train of Ca2+ spikes gives
      rise to repetitive loop-like movements. When sperm swim in a concentration
      gradient of the attractant, the Ca2+ spikes and the stimulus function are
      synchronized, suggesting that precise timing of Ca2+ spikes controls navigation.
      We identified the peptide asterosap as a chemotactic factor of the starfish
      Asterias amurensis. The Ca2+ spikes and swimming behavior of sperm from starfish
      and sea urchin are similar, implying that the signaling pathway of chemotaxis has
      been conserved for almost 500 million years.

PMID- 16001083
TI  - Distinct regulation of histone H3 methylation at lysines 27 and 9 by CpG
      methylation in Arabidopsis.
AB  - Transcriptional activity and structure of chromatin are correlated with patterns
      of covalent DNA and histone modification. Previous studies have revealed that
      high levels of histone H3 dimethylation at lysine 9 (H3K9me2), characteristic of
      transcriptionally silent heterochromatin in Arabidopsis, require hypermethylation
      of DNA at CpG sites. Here, we report that CpG hypermethylation characteristic of
      heterochromatin specifically prevented H3K27 trimethylation (H3K27me3). H3K27
      mono- and dimethylation mark silent heterochromatin independently of DNA
      methylation. Upon loss of CpG methylation, there was target-specific enrichment
      of H3K27me3 in heterochromatin that correlated with transcriptional reactivation.
      Moreover, using the kyp mutant affected in H3K9me2, we showed that changes in
      H3K27me3 occurred independently of the levels of H3K9me2. Therefore, CpG
      methylation provides distinct and direct information for a specific subset of
      histone methylation marks. The observed independence of the regulation of H3K9
      and H3K27 methylation by CpG methylation refines the recently proposed
      combinatorial histone code involving these two marks.

PMID- 16001084
TI  - The DAZL family proteins are PABP-binding proteins that regulate translation in
      germ cells.
AB  - DAZL proteins are germ-cell-specific RNA-binding proteins essential for
      gametogenesis. The precise molecular role of these proteins in germ-cell
      development remains enigmatic; however, they appear to function in the cytoplasm.
      In order to directly address the function of vertebrate DAZL proteins, we have
      used Xenopus laevis oocytes as a model system. Here we demonstrate that members
      of this family, including Xdazl, mouse Dazl, human DAZL, human DAZ and human
      BOULE, have the ability to stimulate translation and function at the level of
      translation initiation. We show that DAZL proteins interact with poly(A)-binding
      proteins (PABPs), which are critical for the initiation of translation. Mapping
      and tethered function experiments suggest that these interactions are
      physiologically important. This leads to an attractive hypothesis whereby DAZL
      proteins activate translationally silent mRNAs during germ cell development
      through the direct recruitment of PABPs.

PMID- 16001085
TI  - HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic
      stresses.
AB  - HIV-1 transactivator Tat uses cellular acetylation signalling by targeting
      several cellular histone acetyltransferases (HAT) to optimize its various
      functions. Although Tip60 was the first HAT identified to interact with Tat, the
      biological significance of this interaction has remained obscure. We had
      previously shown that Tat represses Tip60 HAT activity. Here, a new mechanism of
      Tip60 neutralization by Tat is described, where Tip60 is identified as a
      substrate for the newly reported p300/CBP-associated E4-type ubiquitin-ligase
      activity, and Tat uses this mechanism to induce the polyubiquitination and
      degradation of Tip60. Tip60 targeting by Tat results in a dramatic impairment of
      the Tip60-dependent apoptotic cell response to DNA damage. These data reveal yet
      unknown strategies developed by HIV-1 to increase cell resistance to genotoxic
      stresses and show a role of Tat as a modulator of cellular protein
      ubiquitination.

PMID- 16001087
TI  - Quantitative single cell determination of ERK phosphorylation and regulation in
      relapsed and refractory primary acute myeloid leukemia.
AB  - We investigated the constitutive activation of the MEK/ERK pathway in acute
      myelogenous leukemia (AML) via a flow cytometric technique to quantitate
      expression of phosphorylated ERK (p-ERK). A total of 42 AML samples (16 newly
      diagnosed, 26 relapsed/refractory) were analyzed. Normal bone marrow CD34+ cells
      (n = 10) had little or no expression of p-ERK, while G-CSF-mobilized CD34+ cells
      exhibited enhanced p-ERK levels. Markedly elevated p-ERK levels were found in
      83.3% of the AML samples, with no differences observed between the newly
      diagnosed and relapsed/refractory samples. Treatment with a MEK inhibitor
      resulted in significantly decreased p-ERK levels in both the newly diagnosed and
      relapsed/refractory samples, which was associated with growth arrest, but not
      apoptosis induction. In summary, we defined conditions for the analysis of MAPK
      signaling in primary AML samples. Normal CD34+ cells expressed very low levels of
      p-ERK, and increased p-ERK levels were found in normal G-CSF-stimulated
      circulating CD34+ cells. Constitutively high p-ERK levels observed in the
      majority of AML samples suggest deregulation of this pathway that appears to be
      independent of disease status. The ability of ERK inhibition to promote growth
      arrest rather than apoptosis suggests that clinical trials of MEK/ERK inhibitors
      may be more effective when combined with chemotherapy.

PMID- 16001086
TI  - Bax-like protein Drob-1 protects neurons from expanded polyglutamine-induced
      toxicity in Drosophila.
AB  - Bcl-2 family proteins regulate cell death through the mitochondrial apoptotic
      pathway. Here, we show that the Drosophila Bax-like Bcl-2 family protein Drob-1
      maintains mitochondrial function to protect cells from neurodegeneration. A pan
      neuronal knockdown of Drob-1 results in lower locomotor activity and a shorter
      lifespan in adult flies. Either the RNAi-mediated downregulation of Drob-1 or
      overexpression of Drob-1 antagonist Buffy strongly enhances the polyglutamine
      induced accumulation of ubiquitinated proteins and subsequent neurodegeneration.
      Furthermore, ectopic expression of Drob-1 suppresses the neurodegeneration and
      premature death of flies caused by expanded polyglutamine. Drob-1 knockdown
      decreases cellular ATP levels, and enhances respiratory inhibitor-induced
      mitochondrial defects such as loss of membrane potential (Deltapsim),
      morphological abnormalities, and reductions in activities of complex I+III and
      complex II+III, as well as cell death. Taken together, these results suggest that
      Drob-1 is essential for neuronal cell function, and that Drob-1 protects neurons
      from expanded polyglutamine-mediated neurodegeneration through the regulation of
      mitochondrial homeostasis.

PMID- 16001088
TI  - Complete remission with bortezomib on plasmocytomas in an end-stage patient with
      refractory multiple myeloma who failed all other therapies including
      hematopoietic stem cell transplantation: possible enhancement of graft-vs-tumor
      effect.

PMID- 16001089
TI  - Loss of P-glycoprotein expression in hematopoietic stem cells does not improve
      responses to imatinib in a murine model of chronic myelogenous leukemia.
AB  - Selective inhibition of the BCR/ABL tyrosine kinase by imatinib has become a
      first-line therapy for chronic myelogenous leukemia (CML). However, BCR/ABL
      positive progenitors often persist despite treatment, and relapse associated with
      resistance to imatinib has been described in many patients with advanced disease.
      Drug efflux by P-glycoprotein (P-gp), as well as point mutations in BCR/ABL
      oncoprotein, has been implicated in the mechanism of resistance to imatinib. In
      this study, we established a murine transplantation model of CML-like
      myeloproliferative disease using Mdr1a/1b-null mice and analyzed the effects of
      loss of P-gp on resistance to imatinib. We found that mice transplanted with
      Mdr1a/1b-null bone marrow (BM) that had been transduced with a BCR/ABL retroviral
      vector displayed similar responses to imatinib, compared with those transplanted
      with BCR/ABL-transduced wild-type BM. In the absence of P-gp, the incidence and
      latency of disease in secondary recipients was not changed in imatinib-treated
      mice, relative to wild-type controls. Furthermore, K562 cells engineered to
      overexpress P-gp remained sensitive to imatinib-induced growth inhibition and
      cell death. Together, our findings suggest that P-gp expression in hematopoietic
      stem cells does not significantly contribute to imatinib resistance in CML.

PMID- 16001090
TI  - Newer antidepressants in the primary care setting.
AB  - Because major depression has negative effects on other disease states, proper
      recognition and treatment of depression are important in the primary care
      setting. Although the perfect antidepressant does not yet exist, newer
      antidepressants have advanced the field. This article will summarize key features
      of 3 newer antidepressants that represent advances in psychopharmacology:
      mirtazapine, which has a dual effect on serotonergic and noradrenergic systems;
      escitalopram, the latest selective serotonin reuptake inhibitor, which is the
      first pure antidepressant stereoisomer in clinical use; and duloxetine, a dual
      reuptake inhibitor of norepinephrine and serotonin that is expected to be
      clinically available in the near future.

PMID- 16001091
TI  - Single-action versus dual-action antidepressants.
AB  - Selective serotonin reuptake inhibitors (SSRIs) have become the most popular
      antidepressants over the last decade, largely because they have a better side
      effect profile than the medications that were widely used previously, the
      tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs).
      The SSRIs mostly have one main mechanism of action, inhibition of serotonin
      reuptake. A few of the TCAs are single action but many are dual action, acting
      mainly on the neurochemicals serotonin and norepinephrine, among others. The
      MAOIs are multiple-action medications, acting on monoamines, which include
      serotonin and norepinephrine. While the selectivity of the SSRIs results in an
      improved side effect profile over the earlier dual-action antidepressants, it may
      also reduce their antidepressant effect. SSRIs may have a slower onset of action,
      result in lower remission rates, and be less effective for the physical symptoms
      associated with depression than TCAs and MAOIs. Newer dual-action medications
      have been developed that inhibit the reuptake of both serotonin and
      norepinephrine. These medications, called serotonin-norepinephrine reuptake
      inhibitors, may have fewer side effects than the earlier dual-action medications
      and potentially reduce the symptoms of depression more effectively than the
      SSRIs.

PMID- 16001092
TI  - The link between depression and physical symptoms.
AB  - Physical symptoms are common in depression, and, in fact, vague aches and pain
      are often the presenting symptoms of depression. These symptoms include chronic
      joint pain, limb pain, back pain, gastrointestinal problems, tiredness, sleep
      disturbances, psychomotor activity changes, and appetite changes. A high
      percentage of patients with depression who seek treatment in a primary care
      setting report only physical symptoms, which can make depression very difficult
      to diagnose. Physical pain and depression have a deeper biological connection
      than simple cause and effect; the neurotransmitters that influence both pain and
      mood are serotonin and norepinephrine. Dysregulation of these transmitters is
      linked to both depression and pain. Antidepressants that inhibit the reuptake of
      both serotonin and norepinephrine may be used as first-line treatments in
      depressed patients who present with physical symptoms. Many physicians consider
      patients to be in remission when their acute emotional symptoms have abated, but
      residual symptoms--including physical symptoms--are very common and increase the
      likelihood of relapse. All symptoms must be measured in order to achieve full
      remission. There are a number of short yet accurate measurement tools (rating
      scales) available that effectively measure the remission of physical symptoms as
      well as emotional symptoms.

PMID- 16001093
TI  - Bridging the communication gap between physicians and their patients with
      physical symptoms of depression.
AB  - Primary care physicians must understand and effectively communicate to their
      patients with depression the importance and process of managing the illness
      because these clinicians are usually the first to diagnose and treat patients
      with depression, especially depression with physical symptoms. Diagnosing and
      treating depression presents physicians and patients with a number of challenges,
      many of which arise because doctors and patients do not share enough information
      with one another. To improve the management of depression, physicians should
      explain how depression is diagnosed, how the individual's depression will be
      treated, how treatment success is defined, what treatment side effects might
      occur and how they will be addressed, and why adhering to the treatment regimen
      is important. Unfortunately, patients might not remember everything their
      physicians say during office visits, and physicians might forget to mention some
      instructions. To make sure that patients understand as much about depression and
      its treatment as possible, physicians should provide patients with resources such
      as pamphlets, videotapes, names of books, and Web site addresses and, if
      possible, enlist a mental health professional to educate the patient and provide
      psychotherapy. Physicians should encourage patients to become actively involved
      in their treatment by recording their symptoms, goals of therapy, side effects,
      and changes in their condition and by voicing their concerns. If primary care
      physicians and patients with depression improve their communication, they will
      ultimately strengthen the doctor-patient relationship and improve the patients'
      depressive symptoms and quality of life.

PMID- 16001094
TI  - Atypical antipsychotics: sleep, sedation, and efficacy.
AB  - Patients with schizophrenia often suffer from sleep disturbances such as
      excessive sleeping and insomnia. Common medications for schizophrenia can have a
      sedative effect on patients. Not all antipsychotic medications have the same
      sedative effect, which is related to dosage and affinity for histamine H1
      receptors. Studies have shown that, compared with conventional antipsychotics,
      atypical antipsychotics such as risperidone, olanzapine, quetiapine, and
      ziprasidone generally cause less sedation yet are as effective in controlling
      psychosis and agitation. Sedation can be troublesome to patients who are trying
      to become re-integrated into society and interfere with their treatment regimen.
      Both persistent sedation and chronic insomnia can be managed by the physician.

PMID- 16001095
TI  - Metabolic changes associated with antipsychotic use.
AB  - In the United States, the risk of type 2 diabetes is currently growing to
      epidemic proportions, with many physicians unaware that disorders such as
      schizophrenia and bipolar disorder naturally place patients at an increased risk
      for diabetes. Another serious concern for physicians is the development of
      metabolic syndrome, also known as syndrome X, in patients suffering from
      schizophrenia. Metabolic syndrome often encompasses medical conditions such as
      weight gain, hypertriglyceridemia, and increased insulin, glucose, and low
      density lipoprotein cholesterol levels. Treatment with atypical antipsychotics
      may increase the risk of metabolic syndrome and diabetes, and physicians need to
      be proactive when treating patients with schizophrenia. Physicians should be
      aware that the treatment of schizophrenia involves the right balance for the
      patient in terms of adverse effects versus benefit, and failing to treat a
      patient's mental illness because of potential medical problems may place the
      patient at an increased risk for more serious problems.

PMID- 16001096
TI  - Recognizing and managing antipsychotic drug treatment side effects in the
      elderly.
AB  - Although atypical antipsychotics differ from conventional antipsychotics in their
      decreased ability to cause reversible drug-induced movement disorders/motor side
      effects such as dystonia, drug-induced parkinsonism, and akathisia and
      potentially persistent drug-induced movement disorders/motor side effects such as
      tardive dyskinesia, no antipsychotic agent completely eradicates this risk.
      Antipsychotic agents are frequently used in facilities for the elderly and in
      general hospitals to treat older patients with behavioral problems. Drug-induced
      movement disorders are more common and more persistent in elderly patients than
      in younger patients, and this problem is exacerbated by the fact that
      antipsychotic medications are often misused by practitioners lacking adequate
      psychopharmacologic training. Movement disorders can be detrimental to an elderly
      patient's quality of life and may transform what were otherwise routine
      activities into difficult tasks. Educational programs are needed to teach primary
      care physicians, specialists, and patients and their families how to identify and
      manage drug-induced movement disorders in order to achieve safer and more
      efficacious care for elderly patients.

PMID- 16001097
TI  - Managing anticholinergic side effects.
AB  - Atypical antipsychotics are associated with a lower risk of extrapyramidal
      symptoms (EPS) and tardive dyskinesia than the conventional antipsychotics;
      however, many atypical antipsychotics can cause other potentially harmful side
      effects such as anticholinergic side effects. Peripheral and central
      anticholinergic side effects can cause physical and mental impairment. Awareness
      of the medications that have the potential to cause anticholinergic side effects
      as well as proper management of these symptoms can aid physicians in treating
      patients who need antipsychotic therapy.

PMID- 16001098
TI  - Superoxide dismutase and myeloperoxidase activities in polymorphonuclear
      leukocytes in acne vulgaris.
AB  - BACKGROUND AND DESIGN: Acne vulgaris frequently occurs in the second decade of
      life. The pathogenesis of the disease is multifactorial and in the present study,
      we aimed to investigate the role of reactive oxygen species in the inflammation
      of acne by determining the activities of myeloperoxidase (MPO) and superoxide
      dismutase (SOD) in polymorphonuclear leukocytes (PMN). MATERIALS AND METHODS:
      Forty-three patients with acne vulgaris and 24 healthy controls were enrolled.
      The severity of the acne was categorized from mild (subjects with only comedonic
      lesions) to severe (subjects with nodulocystic lesions). SOD and MPO activities
      in PMN were measured spectrophotometrically. RESULTS: There was no significant
      difference in the activity of MPO between the patients and controls.However, SOD
      activity in PMN was significantly lower in the patients than in the controls
      (p<0.001). Nocorrelation was detected between the activities of enzymes and the
      severity of the disease. CONCLUSION: Propionibacterium acnes may not play a
      primary role in the pathogenesis of acne as a bacterium. However, the low
      activity of SOD in PMN may be responsible for the increased levels of superoxide
      anion radicals in the epidermis. New anti-acne drugs should include substances
      with lymphocyte stimulating and anti-oxidative properties.

PMID- 16001099
TI  - Epidemiology of Darier's Disease in Slovenia.
AB  - AIM: To present a retrospective and prospective epidemiological and clinical
      study on Darier disease in Slovenia. RESULTS: Data on 77 DD patients was
      collected in the period 1973 to 2003 from the major dermatological departments
      and outpatient units in Slovenia. The prevalence of Darier disease in Slovenia is
      calculated at 3.8/100000 inhabitants. The ratio of affected/unaffected family
      members is 0.355. The comparison of two groups of DD patients (younger and older
      than 19 years) for the onset of the disease did not differ significantly although
      in two thirds of patients DD appeared for the first time before the age of 19
      years. CONCLUSION: The epidemiological and clinical data on Darier's disease in
      Slovenia conform to similar reports with the exception of the higher prevalence
      of the disease in Slovenia. UV radiation seems to be an important triggering
      factor and therefore it is reasonable to advise DD patients to avoid sun
      exposure.

PMID- 16001100
TI  - Craniofacial cavernous hemangioma: succesful treatment with methylprednisolone.
AB  - Systemic corticosteroid treatment is reported as effective for problematic
      cutaneous hemangiomas occuring in infancy, and depend on the dose, the duration
      of treatment, and the age at which the course of drugs is initiated. A 7-month
      old female infant with extended cavernous hemangioma on the left part of
      forehead, face,and neck which appeared 15 days after birth is presented. She was
      successfully treated with oral methylprednisolone (initial doses of 3 mg/kg/daily
      and reduced in steps over 6 months) with significant involution of the lesions
      and with good aesthetic results. The oral corticosteroid treatment is an
      efficient medical therapy for common extended cavernous infantile hemangiomas
      with accelerated growth if initiated early in the proliferative phase.

PMID- 16001101
TI  - Scrotal calcinosis: pathogenesis and case report.
AB  - Scrotal calcinosis (SC) is a rare and benign condition defined as the existence
      of multiple calcified nodules within scrotal skin. We report the case of a 39
      year-old male patient with a three-month history of scrotal tumours that
      increased rapidly in number and size. Histopathological and immunohistochemical
      investigations showed no evidence of epithelial structure. Whether SC is
      idiopathic or the result of the calcification of pre-existing cysts is still a
      controversial issue. In some cases, as well as in our case, no evidence of cystic
      structure was found around calcified material, despite minutely careful studies.
      This suggests that SC might be truly idiopathic.

PMID- 16001102
TI  - Pyoderma gangraenosum associated with autoimmune thyreopathy and hyperandrogenic
      syndrome.
AB  - An unusual clinical appearance and course of pyoderma gangraenosum (PG) in a 35
      year-old woman is presented. Signs of both the ulcerative and vegetative forms of
      PG were expressed. The association of two systemic diseases, the autoimmune
      thyreopathy and the hyperandrogenic syndrome were observed in a female. The
      recommended conventional therapy for PG: corticosteroids, antibiotics,
      cyclosporine and cyclophosphamide yielded a poor response, whereas after
      thyroidectomy and reaching an euthyroid state the symptoms receded. This close
      association of PG and autoimmune thyreopathy supports the autoimmune concept of
      PG.

PMID- 16001103
TI  - Kindler syndrome: a case report and proposal for clinical diagnostic criteria.
AB  - Kindler syndrome is a rare hereditary disorder characterized by acral blister
      formation in infancy and childhood, progressive poikiloderma, cutaneous atrophy
      and increased photosensitivity. Since it was first described in 1954, less than
      100 cases have been reported worldwide. Recently it has been reported that
      Kindler syndrome is the first genodermatosis caused by a defect in the actin
      extracellular matrix linkage, and the gene was mapped to chromosome 20p12.3. The
      clinical features of the syndrome have been annotated by different authors but
      the definite of criteria to confirm the diagnosis have not yet been generally
      accepted. We report a case of Kindler syndrome that presents a full spectrum of
      clinical manifestations, and we propose a set of clinical criteria for diagnosis.

PMID- 16001104
TI  - The New Jersey Medical School.
AB  - The New Jersey Medical School (NJMS) was the first medical school in the state of
      New Jersey. Its creation required the vision and support of many, including a
      group of leaders at the Jersey City Medical Center, century old Seton Hall
      University and the Archdiocese of Newark. Chartered in 1954 as Seton Hall College
      of Medicine, it opened its doors in Jersey City in 1956. It was renamed as the
      New Jersey College of Medicine (1965-1970), and since 1970 as New Jersey Medical
      School.

PMID- 16001105
TI  - Differential behavioral effects of the antidepressants reboxetine, fluoxetine,
      and moclobemide in a modified forced swim test following chronic treatment.
AB  - RATIONALE: The forced swim test (FST) is the most widely used model for assessing
      potential antidepressant activity in rodents following acute or short-term
      treatment. However, few studies have compared the effects of short- and long-term
      antidepressant treatment on behaviors in the test, despite the need to treat
      patients chronically to produce clinical effects. OBJECTIVES: The current studies
      examined whether antidepressants from different classes produce different
      behavioral effects following short-term treatment and whether such effects change
      following administration for a longer duration. METHODS: The effects of
      administering short-term (3 days) and long-term (14 days) treatments of
      antidepressants from three different chemical classes with distinct mechanisms of
      action via osmotic minipump were examined: the selective norepinephrine reuptake
      inhibitor reboxetine (10 and 60 mg kg(-1) day(-1)), the selective serotonin
      reuptake inhibitor fluoxetine (2.5 and 15 mg kg(-1) day(-1)), and the reversible
      inhibitor of monoamine oxidase moclobemide (2.5 and 15 mg kg(-1) day(-1)). All
      testing was carried out in a 15-min test with no preswim session in order to
      negate any confounding aspect of an induction procedure. RESULTS: The majority of
      antidepressant-sensitive behavioral changes were observed in the first 5 min of
      the test. The low dose of reboxetine failed to alter behavior in the test after 3
      days but significantly decreased immobility and increased climbing behavior
      following administration for 14 days, whereas the high dose of reboxetine was
      equally effective following 3 and 14 days of treatment. In a similar fashion, the
      low dose of fluoxetine failed to alter behavior in the test following 3 days, but
      showed an augmented response on immobility and increased swimming following
      administration for 14 days. The high dose of fluoxetine was slightly more
      effective at reducing immobility following administration for 14 days than 3
      days. The low dose of moclobemide decreased immobility and increased climbing
      behavior following treatment for 3 days, but increases in both swimming and
      climbing behaviors were measured following treatment for 14 days. Treatment with
      the high dose of moclobemide for 3 days decreased immobility and increased
      swimming, whereas treatment for 14 days significantly increased both active
      behaviors (swimming and climbing). CONCLUSIONS: Antidepressants from three
      different classes produce different effects on active behaviors in the FST. The
      effects of antidepressants were augmented following chronic administration for 14
      days, especially when given at low doses. This suggests that modifications of the
      FST can be used to examine the onset of action of antidepressant agents produced
      by long-term administration.

PMID- 16001107
TI  - Unexpected placebo response in premenstrual dysphoric disorder: implication of
      endogenous opioids.

PMID- 16001106
TI  - Cortical glutamate-dopamine interaction and ketamine-induced psychotic symptoms
      in man.
AB  - RATIONALE: The noncompetitive glutamate N-methyl-D: -aspartate receptor
      antagonist ketamine induces transient psychotic symptoms in man. Involvement of
      dopaminergic mechanisms in these effects has been suggested. OBJECTIVES: The
      purpose of this article is to study the effects of ketamine on extrastriatal
      dopamine receptor availability in healthy subjects and extracellular dopamine
      levels in rat cortex. MATERIALS AND METHODS: The effect of computer-driven
      subanesthetic ketamine infusion on cortical dopamine release was studied in
      healthy male subjects using a controlled study design. Dopamine D2/D3 receptor
      availability was quantified using positron emission tomography (PET) and [11C]FLB
      457. A conventional region of interest-based analysis and voxel-based analysis
      was applied to the PET data. The ketamine-induced cortical dopamine release in
      rats was studied using in vivo microdialysis. RESULTS: Ketamine infusion reduced
      significantly the [11C]FLB 457 binding potential (BP) in the posterior
      cingulate/retrosplenial cortices, suggestive of increased dopamine release. This
      brain imaging finding was further supported by a microdialysis experiment in rats
      showing that ketamine increased the extracellular dopamine concentration by up to
      200% in the retrosplenial cortex. Ketamine-induced psychotic symptoms were
      associated with changes in the [11C]FLB 457 BP in the dorsolateral prefrontal and
      anterior cingulate cortices. CONCLUSIONS: Our results suggest that cortical
      dopaminergic mechanisms have a role in the emergence of ketamine-induced
      psychosis-like symptoms in man. The glutamate-dopamine interaction in the
      posterior cingulate during ketamine infusion is well in line with the recent
      functional and structural imaging studies suggesting involvement of this cortical
      area in the development of schizophrenic psychosis.

PMID- 16001108
TI  - Sex-related elevation in cortisol during chronic treatment with alprazolam
      associated with enhanced cognitive performance.
AB  - OBJECTIVE: There is evidence of more widespread use and abuse of benzodiazepines
      (BZPs) among elderly women. However, factors underlying this observation are
      poorly understood but could be related to more intense withdrawal reactions,
      which are a major risk factor for continued BZP use. We previously reported
      elevations in interdose morning plasma cortisol levels in healthy elderly
      individuals after chronic treatment with alprazolam, possibly consistent with
      increased hypothalamic-pituitary-adrenal (HPA) axis activity and drug withdrawal.
      In this study, we examined sex-related differences in this population. METHOD:
      Twenty-five cognitively intact healthy elderly (13 women and 12 men) participated
      in a parallel, double-blind, placebo-controlled study that included a group that
      received acute and chronic (3 weeks) treatment with alprazolam (0.5 mg b.i.d.).
      RESULTS: Elderly women, but not men, experienced significant elevations in
      interdose morning plasma cortisol levels over 3 weeks of chronic treatment with
      alprazolam (0.5 mg b.i.d.) compared to placebo. In addition, higher morning
      plasma cortisol levels were significantly associated with better cognitive
      performance but not with higher plasma drug levels or greater degree of tolerance
      development to an acute alprazolam challenge. CONCLUSION: Elderly females
      experienced a greater interdose activation of the HPA axis during treatment with
      therapeutic doses of alprazolam than men, which could be related to drug
      withdrawal.

PMID- 16001109
TI  - Effects of caffeine on performance and mood: withdrawal reversal is the most
      plausible explanation.
AB  - RATIONALE: Although it is widely believed that caffeine can enhance human
      performance and mood, the validity of this belief has been questioned, giving
      rise to debate. The central question is whether superior performance and mood
      after caffeine represent net benefits, or whether differences between caffeine
      and control conditions are due to reversal of adverse withdrawal effects.
      OBJECTIVES: To provide a focussed review of relevant experimental studies with
      the aim of clarifying current understanding regarding the effects of caffeine on
      human performance and mood. METHODS: To avoid the shortcomings of standard
      placebo-controlled studies, which are ambiguous due to failure to control for the
      confounding influence of withdrawal reversal, three main experimental approaches
      have been employed: studies that compare consumers and low/non-consumers, pre
      treatment and ad lib consumption studies, and long-term withdrawal studies.
      RESULTS: Of the three approaches, only long-term withdrawal studies are capable
      of unambiguously revealing the net effects of caffeine. Overall, there is little
      evidence of caffeine having beneficial effects on performance or mood under
      conditions of long-term caffeine use vs abstinence. Although modest acute effects
      may occur following initial use, tolerance to these effects appears to develop in
      the context of habitual use of the drug. CONCLUSIONS: Appropriately controlled
      studies show that the effects of caffeine on performance and mood, widely
      perceived to be net beneficial psychostimulant effects, are almost wholly
      attributable to reversal of adverse withdrawal effects associated with short
      periods of abstinence from the drug.

PMID- 16001110
TI  - Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs
      olanzapine on body weight and prolactin secretion in female rats.
AB  - RATIONALE: Atypical antipsychotic drug (APD)-induced weight gain causes non
      compliance, increasing the risk of relapse and medical complications. OBJECTIVES:
      In an animal model, we assessed body weights, food intake, body fat/lean body
      mass contents and blood serum levels of glucose and lipids in female rats treated
      with olanzapine (Experiment 1). Also, we investigated the effect of aripiprazole
      vs olanzapine treatment on weight gain (WG) and plasma prolactin secretion in two
      strains (Wistar and Sprague-Dawley) and in two housing conditions (singly and
      group housed; Experiment 2). METHODS: In Experiment 1, Wistar females received
      either vehicle or olanzapine (5.0 mg kg(-1), p.o.) twice daily for 14 days. In
      Experiment 2, female rats (Wistar or Sprague-Dawley), housed singly or in groups,
      received either vehicle, aripiprazole (2.0-8.0 mg kg(-1), p.o.), or olanzapine
      (1.0-10 mg kg(-1), p.o.) twice daily for 7 days. Body weights and food intake
      were assessed daily. Body composition and blood assays were analyzed at the end
      of the treatment. RESULTS: WG induced by chronic olanzapine treatment was
      characterised by hyperphagia, increased body fat, and serum free fatty acid
      content and reduced lean tissue and serum glucose content. Subchronic
      aripiprazole treatment resulted in rapid and robust WG similar to those observed
      with olanzapine. In spite of similar effects on body weight, aripiprazole and
      olanzapine stimulated markedly different patterns of prolactin secretion. Body
      weight changes and prolactin secretion induced by these APDs were significantly
      modulated by housing and by strain. CONCLUSION: Assessment of body weight in the
      present model may not have predictive validity, and other measures may be needed
      to differentiate between WG-inducing and weight-neutral drugs.

PMID- 16001111
TI  - A functional MRI study of the effects of bromocriptine, a dopamine receptor
      agonist, on component processes of working memory.
AB  - RATIONALE: Dopamine is abundant in the prefrontal cortex and striatum, regions
      implicated in working memory processes. Monkey studies suggest that
      subpopulations of prefrontal neurons are sensitive to component processes of
      working memory, and that dopaminergic actions at D1 and D2 receptors
      differentially affect these neurons. However, it is not known to what extent the
      effects of dopaminergic stimulation may differ in human subjects across the
      processing stages of working memory, and whether these effects are found
      throughout the network of task-related brain regions. OBJECTIVE: In this study we
      tested the effects of the D2 dopamine agonist bromocriptine during the
      performance of a delayed recognition task using functional magnetic resonance
      imaging (fMRI). METHODS: We measured blood oxygenation level dependent (BOLD)
      signals as subjects performed a spatial and object delayed recognition task.
      Subjects were scanned twice, once following 1.25 mg of bromocriptine and once
      following lactose placebo in a randomized double-blind design. Using an event
      related design allowed for separate investigation of encoding, delay, and
      response period effects of dopaminergic stimulation. RESULTS: A group analysis
      revealed that bromocriptine treatment decreased activity in the task network at
      encoding and increased activity at response. There was no clear pattern of change
      in the delay period network. Across subjects, these BOLD signal changes were
      accompanied by reductions in accuracy and increases in response time during
      delayed recognition for spatial and object information. CONCLUSIONS: Decreased
      activity during encoding suggests that hyperdopaminergic stimulation may have
      reduced stimulus encoding processes, contributing to impaired performance.

PMID- 16001112
TI  - Deletion of the beta 2 nicotinic acetylcholine receptor subunit alters
      development of tolerance to nicotine and eliminates receptor upregulation.
AB  - RATIONALE: Chronic nicotine exposure induces both tolerance and upregulation of
      [3H]nicotine binding sites in rodent and human brain. However, the mechanism for
      chronic tolerance is unclear because a direct relationship between tolerance and
      receptor upregulation is not consistently observed. OBJECTIVES: In the present
      experiments, the role of beta2* nicotinic acetylcholine receptors (nAChRs) on
      tolerance development and nAChR upregulation was examined following chronic
      nicotine treatment of beta2 wild-type (+/+), heterozygous (+/-), and null mutant
      (-/-) mice. METHODS: Saline or nicotine (1, 2, or 4 mg/kg/h) was infused
      intravenously for 10 days. Locomotor activity and body temperature responses were
      measured before and after nicotine challenge injection to observe changes in
      nicotine sensitivity. [3H]Epibatidine binding was then measured in ten brain
      regions. RESULTS: Beta2+/+ mice developed dose-dependent tolerance and
      upregulation of [3H]epibatidine binding sites. In contrast, beta2-/- mice,
      initially less sensitive to acute nicotine's effects, became more sensitive
      following treatment with the lowest chronic dose (1 mg/kg/h). Beta2-/- mice
      treated with 4.0 mg/kg/h nicotine were no longer supersensitive, indicating that
      tolerance developed at this higher dose. However, these changes in nicotine
      sensitivity occurred in the absence of any nAChR changes in either low- or high
      affinity [3H]epibatidine sites. Responses of beta2+/- mice were intermediate
      between wild-type and mutant mice. CONCLUSIONS: Upregulation of nAChRs in vivo
      requires the presence of the beta2 subunit. Changes in nicotine sensitivity
      occurred both in the presence (beta2+/+) and absence (beta2-/-) of beta2* nAChRs
      and suggest that mechanisms involving both beta2* and non-beta2* nAChR subtypes
      modulate adaptation to chronic nicotine exposure.

PMID- 16001113
TI  - Effects of paroxetine on cardiovascular response to mental stress in subjects
      with a history of coronary artery disease and no psychiatric diagnoses.
AB  - RATIONALE: Paroxetine may decrease mental stress-induced cardiovascular responses
      and so benefit individuals with heart disease, even those with no psychiatric
      illness. OBJECTIVES: The effects of paroxetine on cardiovascular measures during
      a speech task were evaluated in psychiatrically healthy subjects with a history
      of coronary artery disease (CAD). METHODS: Eight subjects completed this double
      blind, placebo-controlled, cross-over study in which each subject took 1 month of
      paroxetine and 4 weeks of placebo in random order. While on each study,
      medication, blood pressure, heart rate, and plasma norepinephrine concentrations
      were measured during a period of relaxation and during a mental stressor. The
      mental stressor consisted of thinking about a stressful topic, speaking about the
      topic, and listening to a tape-recorded replay of the speech. RESULTS: While on
      paroxetine, systolic blood pressure and diastolic blood pressure were 10-15%
      lower (p < 0.005) during the stressor, relative to measures obtained while on
      placebo. Pulse and plasma norepinephrine concentrations during stress trended
      lower during paroxetine treatment but did not reach statistical significance.
      CONCLUSION: Paroxetine has antihypertensive properties during periods of
      psychological stress in psychiatrically healthy subjects with a history of CAD,
      and so should be evaluated for potential cardio-protective qualities.

PMID- 16001114
TI  - Differential effects of clozapine and haloperidol on interval timing in the
      supraseconds range.
AB  - The effects of clozapine (0.6, 1.2, and 2.4 mg/kg) and haloperidol (0.03, 0.06,
      and 0.12 mg/kg) on the timing of 10, 30, and 90-s intervals were characterized in
      rats. Each drug's effect on timing behavior was assessed following
      intraperitoneal injections using a variant of the peak-interval procedure.
      Although haloperidol proportionately shifted peak times rightward in a manner
      consistent with a decrease in clock speed, clozapine exerted the opposite effect
      and proportionately shifted peak times leftward in a manner consistent with an
      increase in clock speed. These results support the proposal that typical
      antipsychotic drugs such as haloperidol and atypical antipsychotic drugs such as
      clozapine exert differential effects on dopaminergic, serotonergic, and
      glutamatergic systems within the cortex and striatum, two brain regions shown to
      be crucial for interval timing.

PMID- 16001115
TI  - Effects of a systemic AMPA/KA and NMDA receptor blockade on pavlovian
      instrumental transfer.
AB  - RATIONALE: Pavlovian stimuli can markedly elevate instrumental responding
      directed toward a common reward, an effect known as pavlovian-instrumental
      transfer (PIT). PIT critically depends on the amygdala and nucleus accumbens
      (ACB); however, little is known yet about its neurochemical basis. OBJECTIVE:
      Here we examined the role of ionotropic glutamate receptors in PIT. METHODS: The
      effects of a systemic blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate/kainate (AMPA/KA) and N-methyl-D: -aspartate (NMDA) receptors on PIT
      and locomotor activity were investigated in rats. RESULTS: The competitive
      AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt
      (CNQX) (1.5 mg/kg i.p.) did not alter the overall rate of lever pressing and left
      PIT intact, i.e. presentation of a pavlovian stimulus significantly enhanced
      instrumental responding. Furthermore, CNQX did not affect horizontal and vertical
      activity in an open field. The non-competitive NMDA receptor antagonist (+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate
      (dizocilpine) (0.08 mg/kg i.p.) elevated the overall rate of lever pressing but
      did not affect PIT. In addition, dizocilpine increased horizontal and decreased
      vertical activity in an open field. CONCLUSIONS: Previous studies imply that the
      training protocol used here induced a general, not outcome-specific, form of PIT
      which is mediated by the central nucleus of the amygdala (CeN) through modulation
      of mesoaccumbens dopamine transmission. Thus, we suggest that an AMPA/KA and NMDA
      receptor blockade did not affect PIT here because the general motivational
      influence of pavlovian stimuli to induce PIT is conveyed by GABAergic projections
      from the CeN to midbrain dopaminergic neurons.

PMID- 16001116
TI  - Potentiation of cocaine-primed reinstatement of drug seeking in female rats
      during estrus.
AB  - RATIONALE: Gender differences exist in the patterns of drug taking in cocaine
      addiction, suggesting that the propensity to relapse varies between men and
      women. Previous reports have shown sex differences in both cocaine-primed and
      conditioned-cued reinstatement of cocaine-seeking behavior, including recent
      evidence that the estrous cycle influences the level of conditioned-cued
      reinstatement. However, the influence of the estrous cycle on cocaine-primed
      reinstatement has not been examined. OBJECTIVE: Accordingly, we assessed the
      influence of sex and estrous cycle status on cocaine-primed reinstatement of drug
      seeking behavior in Sprague-Dawley rats. METHODS: Intact male and female rats
      were trained to lever press to self-administer intravenous cocaine (0.5 mg/kg
      every infusion; fixed ratio 1, 20-s time-out following each infusion), followed
      by prolonged extinction training, and subsequently tested for the ability of a
      cocaine-priming injection (0, 5, or 10 mg/kg i.p.) to reinstate extinguished
      cocaine seeking (i.e., nonreinforced lever responding). RESULTS: Despite no
      differences in cocaine intake between male and female rats, females responded
      more on the cocaine-paired lever during self-administration and extinction
      relative to males. Subsequently, both males and females exhibited a dose
      dependent cocaine-primed reinstatement of extinguished drug-seeking behavior.
      Moreover, females in estrus exhibited significantly higher reinstatement than
      either males or non-estrus females, following a high-dose (10 mg/kg) cocaine
      prime. CONCLUSIONS: Estrus females display heightened sensitivity to the
      motivational and/or stimulant effects of cocaine, suggesting that hormonal state
      modulates drug craving and propensity for drug relapse in cocaine addicts.

PMID- 16001118
TI  - Reversal of isolation-rearing-induced PPI deficits by an alpha7 nicotinic
      receptor agonist.
AB  - RATIONALE: The alpha7 subtype of the nicotinic receptor plays an important role
      in auditory sensory gating. Schizophrenics show deficient sensory gating and
      abnormalities in the number and regulation of nicotinic receptors. Prepulse
      inhibition (PPI) deficits exhibited by isolation-reared rats are thought to model
      the sensorimotor gating deficits seen in schizophrenia. OBJECTIVE: To examine the
      role of nicotinic alpha7 receptors in the isolation-rearing rat model, we tested
      whether the selective alpha7 receptor agonist (R)-N-(1-Azabicyclo[2.2.2]oct-3
      yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A) could reverse isolation
      rearing-induced PPI deficits, and investigated alpha7 receptor RNA expression in
      the hippocampus, prefrontal cortex, cerebellum, nucleus accumbens and thalamus,
      and alpha7 receptor protein expression in the hippocampus of isolation- and group
      reared rats. METHOD: Rats reared in isolation or groups of five from weaning were
      tested in the PPI paradigm under conditions of variable inter-stimulus interval
      (ISI) (pulse = 110 dB/50 ms; prepulse = 75 dB/30 ms; ISI = 30, 100 and 300 ms) 30
      min following administration of compound A (3.2-10 mg/kg i.p.). Alpha7 receptor
      expression was measured by TaqMan RT-PCR (total RNA) and autoradiography
      (protein). RESULTS: Isolation-rearing-induced PPI deficits were attenuated by
      both doses of compound A at 100-ms ISI and by 10 mg/kg at 300-ms ISI. Expression
      of alpha7 receptor RNA and protein was unaltered in isolation-reared rats.
      CONCLUSION: Although altered alpha7 receptor expression may not underlie the
      phenotype of isolation-reared rats, the activation of these receptors may be of
      benefit in re-establishing efficient gating function.

PMID- 16001117
TI  - Nicotinic modulation of neuronal networks: from receptors to cognition.
AB  - RATIONALE: Nicotine affects many aspects of human cognition, including attention
      and memory. Activation of nicotinic acetylcholine receptors (nAChRs) in neuronal
      networks modulates activity and information processing during cognitive tasks,
      which can be observed in electroencephalograms (EEGs) and functional magnetic
      resonance imaging studies. OBJECTIVES: In this review, we will address aspects of
      nAChR functioning as well as synaptic and cellular modulation important for
      nicotinic impact on neuronal networks that ultimately underlie its effects on
      cognition. Although we will focus on general mechanisms, an emphasis will be put
      on attention behavior and nicotinic modulation of prefrontal cortex. In addition,
      we will discuss how nicotinic effects at the neuronal level could be related to
      its effects on the cognitive level through the study of electrical oscillations
      as observed in EEGs and brain slices. RESULTS/CONCLUSIONS: Very little is known
      about mechanisms of how nAChR activation leads to a modification of electrical
      oscillation frequencies in EEGs. The results of studies using pharmacological
      interventions and transgenic animals implicate some nAChR types in aspects of
      cognition, but neuronal mechanisms are only poorly understood. We are only
      beginning to understand how nAChR distribution in neuronal networks impacts
      network functioning. Unveiling receptor and neuronal mechanisms important for
      nicotinic modulation of cognition will be instrumental for treatments of human
      disorders in which cholinergic signaling have been implicated, such as
      schizophrenia, attention deficit/hyperactivity disorder, and addiction.

PMID- 16001119
TI  - A single injection of the kappa opioid antagonist norbinaltorphimine increases
      ethanol consumption in rats.
AB  - RATIONALE: Kappa opioid receptor (KOR) agonists interfere with the reinforcing
      effects of drugs of abuse. KOR agonists decrease heroin, cocaine, and ethanol
      self-administration, and block heroin and cocaine conditioned place preference
      (CPP) in rats. However, KOR agonists also produce emesis and dysphoria, making it
      difficult to determine if their effects on self-administration are due to an
      action on reward mechanisms or are secondary to the drug's direct aversive
      effects. Assuming that endogenous KOR ligands modulate circuits involved in drug
      and alcohol reward, selective KOR antagonists can be used to clarify these
      issues. If KOR antagonists increase drug self-administration then it is likely
      that endogenous KOR agonists directly modulate drug intake. OBJECTIVES: To
      determine the effects of nor-BNI, the highly selective KOR antagonist, on ethanol
      consumption and CPP. METHODS: Thirty-eight male Lewis rats were given free access
      to ethanol until stable self-administration was achieved. Animals were then
      administered a single injection of nor-BNI (10 mg kg(-1)) while ethanol intake
      was monitored. RESULTS: A single injection of nor-BNI induces a long-lasting
      increase in ethanol consumption, but does not induce a CPP. A high/low split
      revealed that this effect was primarily due to an increase in drinking in nor-BNI
      treated high drinkers, which drank significantly more than saline-treated high
      drinkers and also drank significantly more when compared to their own
      pretreatment baseline. CONCLUSIONS: Blocking the KOR system increases ethanol
      self-administration, suggesting that the decrease in self-administration seen
      with KOR agonists is due to a direct modulation of reward circuitry.

PMID- 16001120
TI  - Censorship by a tobacco company.

PMID- 16001121
TI  - Effect of Thunbergia laurifolia, a Thai natural product used to treat drug
      addiction, on cerebral activity detected by functional magnetic resonance imaging
      in the rat.
AB  - RATIONALE: Thunbergia laurifolia Linn. (TL) is an herbal medicine used to treat
      alcohol and drug addiction in Thai traditional medicine. A previous study
      demonstrated that an extract of TL increases rat striatal dopamine release in
      vitro. OBJECTIVES: This study determined whether a methanol extract of TL altered
      rat brain region activity using in vivo functional nuclear magnetic resonance
      imaging (fMRI) in a manner consistent with the observed effects in vitro on
      dopamine release. METHODS: fMRI was performed on a 2.35-T Bruker MR system. MR
      images were acquired from rat brain using the rapid acquisition relaxation
      enhanced sequence (field of view 50 mm). The imaging parameters used for the
      anatomical scan yielded an in-plane spatial resolution of 0.2x0.2 mm. Consecutive
      single-slice functional imaging over the rat brain investigated the changes in
      signal intensity in various parts of the brains induced by TL (200 mg/kg, i.p.)
      or vehicle administration. RESULTS: These demonstrate that TL increased signal
      intensity in various brain areas such as nucleus accumbens, globus pallidus,
      amygdala, frontal cortex, caudate putamen and hippocampus. These are similar to
      those reported previously to show effects after either cocaine or amphetamine
      administration. Physiological variables were not affected by the injection of TL
      (200 mg/kg, i.p.), but there was a small decrease in arterial blood pressure.
      CONCLUSIONS: The results indicate that TL increases significant neuronal activity
      in specific brain regions responsible for reward and locomotor behaviour (fixed
      effect analysis); however, there is no significant difference between TL and
      vehicle-treated groups with random-effect analysis (population statistic). The
      active compound(s) in TL responsible for the pharmacological effects of TL remain
      to be identified.

PMID- 16001123
TI  - Dose, duration, and pattern of nicotine administration as determinants of
      behavioral dependence in rats.
AB  - RATIONALE: Relatively little is known about the role of dose, duration, and
      pattern of nicotine exposure in the development of dependence. Disruption of
      learned behavior during antagonist-precipitated withdrawal can be a sensitive,
      quantitative measure of behavioral dependence. OBJECTIVES: The present study
      sought to determine whether behavioral dependence upon nicotine could be induced
      in rats and, if so, what exposure conditions were essential for inducing it. Our
      primary focus was on whether continuous exposure over several days was necessary
      to produce dependence. METHODS: Male Sprague-Dawley rats were trained to lever
      press under fixed-ratio 10 schedules of food reinforcement during daily, 15-min
      experimental sessions. Nicotine was then administered s.c. via osmotic minipumps
      that delivered various nicotine dosage regimens, some including 24-h nicotine
      free periods, to manipulate pattern of exposure. The presence of dependence was
      tested with challenges with the nicotinic acetylcholine receptor antagonist,
      mecamylamine, or during spontaneous withdrawal. RESULTS: After 7 days of 3, 6,
      and 12 mg kg(-1) day(-1) nicotine administration, response rates were
      significantly reduced in nicotinized, but not in saline-treated rats following
      mecamylamine challenges. Subsequent studies demonstrated that 4 days, but not 3
      days, of cumulative 3 mg kg(-1) day(-1) nicotine administration was sufficient to
      induce dependence. The induction of dependence could be prevented by imposing a
      nicotine-free period between the first and second days during these 4-day
      regimens but not at other times. CONCLUSION: Behavioral dependence upon nicotine
      can be induced in the rat, and its induction is dependent upon its cumulative
      duration and pattern of exposure suggesting that tobacco dependencies could be
      controlled by similar determinants.

PMID- 16001122
TI  - Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4
      methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and
      locomotion in freely moving rats.
AB  - RATIONALE: Like amphetamine, a locomotor-activating dose of 3,4
      methylenedioxymethamphetamine (MDMA) predominantly excites striatal single-unit
      activity in freely moving rats. Although both D1- and D2-like dopamine (DA)
      receptors play important roles in this effect, MDMA, unlike amphetamine, strongly
      increases both DA and serotonin (5-HT) transmission. OBJECTIVES: This study was
      conducted to investigate the 5-HT receptor mechanisms underlying the striatal
      effects of MDMA. METHODS: We recorded the activity of >200 single units in the
      striatum of awake, unrestrained rats in response to acute MDMA administration (5
      mg/kg) combined with the selective blockade of either 5-HT2A or 5-HT2C/B
      receptors. RESULTS: Prior administration of SR-46349B (a 5-HT2A antagonist 0.5
      mg/kg) blocked nearly all MDMA-induced striatal excitations, which paralleled its
      significant attenuation of MDMA-induced locomotor activation. Conversely, prior
      administration of SB-206553 (a 5-HT2C/B antagonist 2.0 mg/kg) had no effect on
      the amount of MDMA-induced locomotor activation or the distribution of single
      unit responses to MDMA. However, a coefficient-of-variation analysis indicated
      significantly less variability in the magnitude of both MDMA-induced neuronal
      excitations and inhibitions in rats that were pretreated with SB-206553 compared
      to vehicle. Analysis of concurrent single-unit activity and behavior confirmed
      that MDMA-induced striatal activation was not merely due to behavioral feedback,
      indicating a primary action of MDMA. CONCLUSION: These results support and extend
      our previous findings by showing that 5-HT2A and 5-HT2C/B receptors
      differentially regulate the expression of MDMA-induced behavioral and striatal
      neuronal responses, either directly or through the modulation of DA transmission.

PMID- 16001124
TI  - Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) and its metabolic
      precursor, gamma-butyrolactone (GBL) in rats.
AB  - RATIONALE: Gamma-hydroxybutyrate (GHB) is becoming an increasingly popular drug
      of abuse. Metabolic precursors of GHB, gamma-butyrolactone (GBL) and 1,4
      butanediol (BDL), are commercially available industrial solvents that may also
      present potential health risks. Relatively little is known about the
      neurobehavioral effects of GHB and its precursors. OBJECTIVE: The aim of the
      present investigation was to characterize the discriminative stimulus effects of
      GHB and its precursor, GBL. METHODS: Male Sprague-Dawley rats were trained to
      discriminate GHB [300 mg/kg, i.g.; n=16] or GBL (150 mg/kg, i.p.; n=8) from
      vehicle under a fixed ratio 20 (FR 20) schedule of food reinforcement. Stimulus
      generalization tests were then conducted with several compounds. RESULTS: GHB and
      GBL produced cross-generalization and BDL was fully substituted for both GHB and
      GBL. Two benzodiazepines, alprazolam and diazepam, and the 5-HT1A agonist,
      buspirone, did not substitute for either training drug nor did ethanol or the
      NMDA antagonists, PCP and ketamine. The GHB antagonist, NCS-382, and the GABA(B)
      antagonist, CGP-35348, blocked the discriminative stimulus effects of GHB but not
      those of GBL. CONCLUSIONS: These findings suggest that GHB and its metabolic
      precursors produce similar subjective effects that differ from those of other
      sedative-hypnotic drugs. Further investigations into the neurochemical actions
      underlying the subjective effects of these drugs are warranted.

PMID- 16001125
TI  - Effect of pattern and number of chronic ethanol exposures on subsequent voluntary
      ethanol intake in C57BL/6J mice.
AB  - RATIONALE: We previously demonstrated that chronic ethanol exposure and
      withdrawal experience significantly increased subsequent voluntary ethanol intake
      in C57BL/6J mice. This study was conducted to examine chronic ethanol conditions
      that optimize this enhanced ethanol-drinking behavior. OBJECTIVES: The purpose of
      this study was to examine whether the pattern and/or number of chronic ethanol
      exposures influence subsequent ethanol intake. METHODS: C57BL/6J mice were
      trained to drink ethanol (15% v/v) in a limited access situation (2 h/day) until
      stable intake was achieved. In experiment 1, mice received two cycles of chronic
      ethanol exposure delivered either in an intermittent [multiple withdrawal (MW)]
      or continuous [continuous exposure (CE)] pattern. One week of daily drinking
      sessions followed each exposure. In experiment 2, mice received either two or
      four cycles of chronic intermittent ethanol exposure (MW), each followed by a
      week of testing sessions. Three additional weeks of ethanol intake testing
      followed the last ethanol (or air) exposure. RESULTS: Experiment 1: Only the MW
      group evidenced a significant increase in ethanol intake compared to controls
      after the first chronic ethanol exposure. Both MW and CE groups consumed more
      ethanol than controls after the second ethanol-exposure period. Experiment 2:
      Ethanol intake in MW mice compared to controls significantly increased after two
      or four cycles of chronic ethanol exposure/withdrawal, and this heightened
      ethanol intake lasted longer in mice that received four cycles of chronic
      intermittent ethanol exposure. CONCLUSIONS: Increased voluntary ethanol intake
      after chronic ethanol exposure and withdrawal experience may be accelerated by
      intermittent (as opposed to continuous) ethanol exposure, and the effect may last
      longer with increased number of such experiences.

PMID- 16001127
TI  - In silico identification and expression analysis of 12 novel CC chemokines in
      catfish.
AB  - Chemokines, a superfamily of chemotactic cytokines involved in recruitment,
      activation, and adhesion of a variety of leukocyte types to inflammatory foci,
      are a crucial component of the immune system of Sarcopterygiian vertebrates.
      Although all mammalian chemokines are believed to have been found, the status of
      these molecules in Actinopterygii was unknown until recently. The identification
      of chemokines in fish species has been complicated by low sequence conservation
      and confusion over expected numbers. Earlier discoveries of single fish
      chemokines coupled with rapidly expanding genetic resources in these species have
      recently provided a foundation for large-scale in silico discoveries of these
      important immune regulators. We report here the identification and expression
      analysis of 12 new CC chemokine sequences from catfish. When added to our
      previous report of 14 catfish CC chemokines, the number of CC chemokines in
      catfish now stands at 26, two more than known from humans. Establishing
      orthologous relationships among the majority of catfish CC chemokines, a newly
      available set of chicken CC chemokines, and their mammalian counterparts remain
      difficult, suggesting high levels of duplication and divergence within individual
      species.

PMID- 16001128
TI  - Differential display analysis reveals the expression of glutathione S-transferase
      omega and novel genes through an ITAM-containing receptor in ascidian
      immunocytes.
AB  - The immunoreceptor tyrosine-based activation motif (ITAM) plays an important role
      in signal transduction through antigen receptors in mammalian lymphocytes. We
      previously reported that an ITAM-containing receptor, ascidian hemocyte ITAM
      containing receptor 1 (AhITAMR1), exists on the hemocyte surfaces of the ascidian
      Halocynthia roretzi, and is involved in both phagocytosis and hemocyte
      aggregation. In this study, we carried out differential display screening of
      upregulated genes during H. roretzi hemocyte aggregation and found that at least
      three genes are upregulated. One encodes glutathione S-transferase omega
      (GSTomega), while the other two encode novel proteins. The expression of all
      three genes was induced by treatment with a specific monoclonal antibody against
      AhITAMR1, while their expression was inhibited by wortmannin, BAPTA-AM, and
      cyclosporin A. We also found that the expression of GSTomega was induced by
      treatment with anti-T cell receptor antibody in mouse peripheral T cells. We
      propose that signal transduction pathways mediated by ITAM-containing receptors
      are conserved from ascidian hemocytes to mammalian T cells.

PMID- 16001126
TI  - The potential role of lamotrigine in schizophrenia.
AB  - RATIONALE: Atypical antipsychotic drugs are the drugs of choice for the treatment
      of schizophrenia. However, despite advances, no treatments have been established
      for patients who fail to improve with the most effective of these, clozapine. The
      inhibition of dopamine transmission through blockade of dopamine D2 receptors is
      considered to be essential for antipsychotic efficacy, but it is postulated that
      modulation of glutamate transmission may be equally important. In support of
      this, symptoms similar to schizophrenia can be induced in healthy volunteers
      using N-methyl-D-aspartate (NMDA) antagonist drugs that are also known to enhance
      glutamate transmission. Furthermore, lamotrigine, which can modulate glutamate
      release, may add to or synergise with atypical antipsychotic drugs, some of which
      may themselves modulate glutamate transmission. OBJECTIVES: We examine the
      evidence for the efficacy of lamotrigine. We consider how this fits with a
      glutamate neuron dysregulation hypothesis of the disorder. We discuss mechanisms
      by which lamotrigine might influence neuronal activity and glutamate
      transmission, and possible ways in which the drug might interact with
      antipsychotic medications. RESULTS: Data from four clinical studies support the
      efficacy of adjunctive lamotrigine in the treatment of schizophrenia. In
      addition, and consistent with a glutamate neuron dysregulation hypothesis of
      schizophrenia, lamotrigine can prevent the psychotic symptoms or behavioural
      disruption induced by NMDA receptor antagonists in healthy volunteers or rodents.
      CONCLUSIONS: The efficacy of lamotrigine is most likely explained within the
      framework of a glutamate neuron dysregulation hypothesis, and may arise primarily
      through the drugs ability to influence glutamate transmission and neural activity
      in the cortex. The drug is likely to act through inhibition of voltage-gated
      sodium channels, though other molecular interactions cannot be ruled out.
      Lamotrigine may add to or synergise with some atypical antipsychotic drugs acting
      on glutamate transmission; alternatively, they may act independently on glutamate
      and dopamine systems to bring about a combined therapeutic effect. We propose new
      strategies for the treatment of schizophrenia using a combination of anti
      dopaminergic and anti-glutamatergic drugs.

PMID- 16001130
TI  - Tension responses to rapid (laser) temperature-jumps during twitch contractions
      in intact rat muscle fibres.
AB  - We examined the tension responses induced by rapid temperature-jumps (T-jumps)
      applied at different times during twitch and tetanic contractions in small intact
      fibre bundles (5-10 fibres) isolated from a fast foot muscle (flexor hallucis
      brevis) of the rat. A rapid T-jump of 2-4 degrees C was induced by a 0.2 ms
      infrared (lambda = 1.32 microm) laser pulse applied to the fibre bundle immersed
      in a 50 microl trough of physiological saline, the temperature of which was
      clamped at different steady temperatures ranging from 10 to 30 degrees C. In a
      tetanic contraction, the tension increased to the same steady level when a
      standard T-jump was applied at different intervals after the onset of
      stimulation; thus, with maximal activation, an enhanced force generation by T
      jump leads to a new steady state. In a twitch contraction, a T-jump induced a
      large, potentiation of tension when it was applied during the rising phase.
      Whereas the twitch relaxation subsequent to a T-jump was faster in all cases, the
      amplitude of the twitch tension potentiation decreased as the T-jump was delayed
      with respect to the stimulus, and there was no increase of tension when a T-jump
      was placed on the relaxation phase of the twitch. The increase of tension induced
      by a T-jump applied on the rising phase resulted in peak tension that was greater
      than the tension in control twitches at the steady post-T-jump temperature;
      therefore tension was higher than that expected on the basis of steady state
      temperature dependence of twitch tension. Whether these effects on a twitch
      contraction arise from differential fibre-heating by a T-jump that leads to
      shortening and development of sarcomere length disorder etc remain unclear.
      However, the findings may be interpreted as indicating that twitch tension
      increment by a T-jump occurs when excitation (the action potential) leading to
      calcium release and thin filament activation occur at the low temperature,
      whereas the crossbridge force-generation processes (and Ca2+-uptake) proceed at
      the higher temperature.

PMID- 16001131
TI  - Impact of patient position on filling phase of urodynamics in women.
AB  - This is a randomised cross-over study designed to access the effect of position
      on urodynamic investigation of women with urinary incontinence. Women were
      investigated in the supine and sitting positions. There was small, not
      statistically significant difference in total bladder volume. Total bladder
      volume was nearer to women's actual bladder capacity in the sitting position.
      There was no difference in bladder volume at first sensation or normal desire in
      both positions. There was a small, not statistically significant difference in
      bladder volume at strong desire and urgency. Women felt strong desire and urgency
      at lower bladder volumes in the sitting position. There was no clear patient
      preference for one position over the other.

PMID- 16001129
TI  - The Toll-like receptors: analysis by forward genetic methods.
AB  - Many genes, and conceivably most genes, are constitutively expressed yet have
      conditional functions. Their products are utilized only under special
      circumstances, and enforce homeostatic regulation. Mutations do not disclose the
      function of such genes unless the proper conditions are applied. The genes that
      encode the Toll-like receptors (TLRs) fall into this category. The TLRs represent
      the principal sensors of infection in mammals. Absent infection, mammals have
      little need for the TLRs; they are essential only when microbes gain access to
      the interior milieu of the host. The function of the TLRs in mammals was first
      disclosed by a spontaneous mutation in a locus called Lps, when it was shown by
      positional cloning to be identical to Tlr4. Random germline mutagenesis has since
      permitted an estimate of the total number of proteins required for TLR signaling
      to the level of tumor necrosis factor (TNF) synthesis and activity, and has also
      shown that these sensors are extremely broad in their ability to detect microbes.
      Ultimately, the TLRs are responsible for most infection-related phenomena, both
      good and bad. These include the development of fever, shock, and tissue injury,
      but also the activation of innate and adaptive effector mechanisms that lead to
      the elimination of microbes.

PMID- 16001132
TI  - Bladder augmentation using Pelvicol implant for intractable overactive bladder
      syndrome.
AB  - The objective of the study was to evaluate the effectiveness of an implant of
      porcine dermis to augment the bladder in women with refractory overactive bladder
      syndrome (OAB). Twelve women underwent a Pelvicol bladder augmentation. A visual
      analogue score for severity of incontinence and a quality of life questionnaire
      was carried out pre-operatively and at 12 months post-operatively. Follow up
      cystoscopy was carried out in three women in addition. Three women were dry and
      cured; five women were significantly improved; two women were slightly improved
      and the procedure was unsuccessful in the remaining two women. There were no
      significant complications and voiding was spontaneous in every case. A bladder
      augmentation using porcine dermis may have a role in the surgical management of
      non-neuropathic women with OAB that has failed to respond to conservative
      therapy.

PMID- 16001133
TI  - Percutaneous transcholecystic biliary interventions using gallbladder anchors:
      feasibility study in the swine.
AB  - The purpose of this study was to report our initial experience with a swine model
      for biliary interventions by using a percutaneous transcholecystic access after
      suture anchor of the gallbladder. Telepaque tablets were given to five pigs to
      opacify the gallbladder. Under fluoroscopy, the opacified gallbladder was
      punctured percutaneously and three suture anchors were used to fix the anterior
      wall of the gallbladder to the abdominal wall. Two weeks later, the gallbladder
      was punctured and access into the distal common bile was obtained through the
      cystic duct. Balloon expandable stents were deployed into the distal common bile
      duct. Follow-up cholangiograms were obtained at 1 and 2 weeks. Necropsy was
      performed after 2 weeks to evaluate the relationship between the gallbladder and
      abdominal wall. Suture anchor placement was successful in all five pigs. One pig
      with a deep and highly positioned gallbladder developed fever, anorexia, and
      vomiting secondary to excessive stretch of the gallbladder. Placement of the
      guidewire through the extremely tortuous and small cystic ducts proved to be the
      most challenging step of the procedure. Metallic stents were successfully
      deployed in all four pigs in which it was attempted. Four animals tolerated the
      procedures without changes in their clinical conditions and no symptoms.
      Successful follow-up cholangiograms were performed at 1 and 2 weeks post-stent
      deployment without complications. All stents remained patent during the follow-up
      period. Necropsy demonstrated close attachment and adherence of the gallbladders
      to the antero-lateral abdominal wall in all four animals. Suture anchoring of the
      gallbladder is feasible in most pigs with superficially located gallbladders.
      This technique allows a safe and repeat access into the biliary system using a
      transcholecystic approach.

PMID- 16001134
TI  - Transpulmonary CT-guided radiofrequency ablation of liver metastasis.
AB  - The percutaneous approach for RF ablation of liver lesions high up in the dome is
      always difficult. The authors describe a transpulmonary approach that may be
      simpler and safer to use.

PMID- 16001135
TI  - Prophylactic residual aneurysmal sac embolization with expandable hydrogel
      embolic devices for endoleak prevention: preliminary study in dogs.
AB  - OBJECTIVE: To explore the feasibility and efficacy of residual aneurysmal sac
      (RAS) embolization with the expandable hydrogel embolic device (EHED) in
      prevention of endoleaks in a surgically created and endoluminally treated
      abdominal aortic aneurysm (AAA). METHODS: In eight dogs, an AAA was created by
      means of side-to-side anastomosis between the infrarenal abdominal aorta and
      inferior vena cava (IVC) with ligation of the IVC above and below the anastomotic
      end, followed by deployment of an endograft with holes. The RAS was then
      embolized with the EHED. One animal was killed immediately after RAS embolization
      and one animal died 12 hr after the procedure. Follow-up aortograms were obtained
      in six animals after 1 day (1 animal), 2 weeks and 6 months (1 animal), and 8
      weeks (4 animals). RESULTS: Four animals had no endoleaks on the follow-up
      aortograms. The remaining two animals with incomplete RAS embolization had
      moderate type III endoleaks. Type I or II endoleaks were not seen in any animals.
      Complications included RAS wall penetration by the devices with platinum wires in
      two animals (nos. 1 and 2), device migration into an aortic circulation through
      the endograft holes in two animals (nos. 2 and 3) or through distal interstices
      between the aortic wall and endograft in one animal (no. 8), aortic occlusion in
      three animals (nos. 3, 7, and 8), and RAS rupture in one animal (no. 7).
      Histologic examination showed expanded hydrogels occupying the RAS with
      associated mature or immature organized thrombus, fibrinous thrombus, or
      degenerate blood cells. CONCLUSION: RAS embolization was feasible with the EHED,
      although additional modifications to the device are required to avoid
      complications. Angiographic and histologic results suggested that RAS
      embolization with the EHED may help in the prevention of endoleaks.

PMID- 16001136
TI  - Long-term results of blunt traumatic renal artery dissection treated by
      endovascular stenting.
AB  - A 20-year-old man was admitted to the emergency department after falling 15 m
      onto the roof of a car and landing on his back. Imaging by computed tomography
      (CT) showed delayed perfusion of the right kidney and no excretion of contrast
      from that kidney on delayed images. Angiography confirmed a localized intimal
      dissection in the right main renal artery. We inserted a balloon-expandable stent
      using a transfemoral approach to successfully repair the dissection. At 4 year
      follow-up, Doppler ultrasound of the right renal artery and renal scintigraphy
      demonstrated preserved function of the right kidney. Our findings support
      endovascular stenting as a safe, effective and efficient treatment for blunt
      renal artery injury.

PMID- 16001138
TI  - A case of aortopulmonary window simulating common arterial trunk presented at the
      age of 13.
AB  - We have reported a patient with aortopulmonary window (APW) simulating truncus.
      In classically defined APW, aorta and main pulmonary artery separate again after
      a distance from the window and form the aortic arch and pulmonary arteries.
      However, in our case, there was no separation and they formed a very large pouch
      from which the great vessels originated. Thus, we believe that we have presented
      the first case of APW simulating truncus, but with two separate semilunar valves.

PMID- 16001137
TI  - CT mapping of the distribution of saline during radiofrequency ablation with
      perfusion electrodes.
AB  - PURPOSE: During radiofrequency (RF) ablation, adjunctive saline increases the
      size of the ablation zone and therefore electrodes that simultaneously deliver
      current and saline have been developed, but the addition of saline also results
      in an irregular ablation zone. Our aim was to study the distribution of saline
      during RF ablation. METHODS: Four patients were treated: 3 with liver metastases
      and 1 with hepatocellular carcinoma (HCC). Two different perfusion electrodes
      were used: a high-perfusion-rate, straight electrode (Berchtold, Germany) and a
      low-perfusion-rate, expandable electrode (RITA Medical Systems, USA). The saline
      perfusate was doped with non-ionic contrast medium to render it visible on CT and
      the electrical conductivity was measured. CT scans were obtained of each
      electrode position prior to ablation and repeated after ablation. Contrast
      enhanced CT was performed 18-24 hr later to demonstrate the ablation zone. All
      treatments were carried out according to the manufacturer's recommended protocol.
      RESULTS: The addition of a small quantity of non-ionic contrast did not alter the
      electrical conductivity of the saline. Contrast-doped saline extravasated beyond
      the tumor in all 3 patients with metastases but was limited in the patient with
      HCC. In some areas where saline had extravasated there was reduced enhancement on
      contrast-enhanced CT consistent with tissue ablation. One patient treated with
      the high-perfusion-rate system sustained a jejunal perforation requiring surgery.
      CONCLUSION: Saline can extravasate beyond the tumor and with the high-perfusion
      rate system this resulted in an undesirable extension of the ablation zone and a
      complication.

PMID- 16001139
TI  - Successful endovascular treatment of iliac vein compression (May-Thurner)
      syndrome in a pediatric patient.
AB  - A 10-year-old boy presented to our clinic with left lower extremity swelling
      present for 1 year with deterioration of symptoms during the prior month.
      Laboratory investigation for deep vein thrombosis was negative. Venography and
      computed tomography scan of the pelvis showed compression of the left common
      iliac vein by the right common iliac artery. A diagnosis of iliac vein
      compression syndrome was made. After venography, endovascular treatment was
      planned. The stenosis did not respond to balloon dilatation and a 12 mm Wallstent
      was placed with successful outcome. The patient's symptoms improved but did not
      resolve completely, probably due to a chronically occluded left superficial
      femoral vein that did not respond to endovascular recanalization. To the best of
      our knowledge, this is the first case of successful endovascular treatment of
      iliac vein compression syndrome with stent placement in a pediatric patient.

PMID- 16001140
TI  - Massive hemorrhage from internal carotid artery pseudoaneurysm successfully
      treated by transcatheter arterial embolization with assessment of regional
      cerebral oxygenation.
AB  - A 54-year-old male presented with intermittent massive hemorrhage from recurrent
      oropharyngeal cancer. The angiogram showed the encasements at the main trunk of
      the left internal carotid artery (ICA) and external carotid artery (ECA).
      Transcatheter arterial embolization (TAE) of the ECA with gelatin sponge
      particles and microcoils was performed. However, hemorrhage recurred several
      hours after the initial TAE. The second angiogram showed a large pseudoaneurysm
      of the ICA developing at the encasement on the initial angiogram. As a simple
      neurologic test, regional cerebral oxygenation (rSO2) was assessed with and
      without manual compression of the common carotid artery (CCA). With compression
      of the left CCA, the rSO2 did not change. We therefore performed isolation of the
      pseudoaneurysm. We embolized proximally and distally to the ICA pseudoaneurysm
      with microcoils and the pseudoaneurysm disappeared. No major complications
      occurred and no massive hemorrhage recurred until death from the cancer. TAE was
      an effective treatment for massive hemorrhage caused by tumor invasion to ICA.
      Assessment of rSO2 was a simple and useful neurologic test predicting the
      cerebral blood flow to prevent complications of TAE.

PMID- 16001141
TI  - Bronchobiliary fistula treated by self-expanding ePTFE-covered nitinol stent
      graft.
AB  - A 71-year-old man, who had undergone right hepatectomy extended to the caudate
      lobe with terminolateral Roux-en-Y left hepatojejunostomy for a Klatskin tumor,
      developed bilioptysis 3 weeks postoperatively due to bronchobiliary fistula.
      Percutaneous transhepatic cholangiography revealed a non-dilated biliary system
      with contrast medium extravasation to the right subphrenic space through a
      resected anomalous right posterior segmental duct. After initial unsuccessful
      internal-external biliary drainage, the fistula was sealed with a VIATORR covered
      self-expanding nitinol stent-graft placed with its distal uncovered region in the
      hepatojejunal anastomosis and the proximal ePTFE-lined region in the left hepatic
      duct. A 10-month follow-up revealed no recurrence of bilioptysis and confirmed
      the complete exclusion of the bronchobiliary fistula.

PMID- 16001142
TI  - Tenecteplase in the treatment of thrombosed hemodialysis grafts.
AB  - A pilot study was carried out to prospectively evaluate the efficacy and safety
      of Tenecteplase (TNKase) using a modified 'lyse and wait" technique with
      percutaneous transluminal angioplasty (PTA) to treat thrombosed hemodialysis
      arteriovenous grafts (AVG)s. Seven patients with eight hemodialysis AVGs were
      treated and followed up to 1 year. Dosing included 1 mg TNKase and 3,000-4,000 U
      of heparin. Technical and clinical success rates were 100% and 88%, respectively.
      No major complications occurred. Primary patency rates at 30, 90, and 180 days
      were 62%, 50%, and 33%, respectively. TNKase, used in this fashion, may be
      comparable to alteplase and reteplase for safe and effective thrombolysis of PTFE
      dialysis grafts.

PMID- 16001143
TI  - Occult mediastinal great vessel trauma: the value of aortography performed during
      angiographic screening for blunt cervical vascular trauma.
AB  - PURPOSE: To determine the value of aortography in the assessment of occult aortic
      and great vessel injuries when routinely performed during screening angiography
      for blunt cerebrovascular injury (BCVI). METHODS: One hundred and one consecutive
      patients who received both aortography and screening four-vessel angiography over
      4 years were identified retrospectively. Angiograms for these patients were
      evaluated, and the incidence of occult mediastinal vascular injury was
      determined. RESULTS: Of the 101 patients, 6 (6%) had angiographically documented
      traumatic aortic injuries. Of these 6 patients, one injury (17%) was unsuspected
      prior to angiography. Four of the 6 (67%) also had BCVI. One additional patient
      also had an injury to a branch of the subclavian artery. CONCLUSION: Routine
      aortography during screening angiography for BCVI is not warranted due to the low
      incidence (1%) of occult mediastinal arterial injury. However, in the setting of
      a BCVI screening study and no CT scan of the chest, aortography may be
      advantageous.

PMID- 16001144
TI  - Salvage of immature arteriovenous fistulas with percutaneous transluminal
      angioplasty.
AB  - The purpose of this study was to assess the value of percutaneous transluminal
      angioplasty (PTA) for the salvage of arteriovenous fistulas (AVFs) that fail to
      mature. From November 1998 to February 2003, 19 patients who were treated with
      PTA due to immature forearm AVFs were selected. Fistulography and PTA were
      performed via a retrograde transvenous approach after direct puncture of the
      fistular vein. Technical success was defined as less than a 30% residual
      stenosis, whereas clinical success was defined as the ability to perform at least
      one session of normal hemodialysis after PTA. Findings of fistulograms, success
      rates of PTA, and patency rates were evaluated. On initial fistulograms, stenoses
      were observed in all cases and 68% (13/19) of the stenoses were located in the
      perianastomotic area of these immature AVFs. The initial technical success rate
      was 84% (16/19). Technical failures comprised two patients with diffuse narrowing
      and segmental thrombosis of the cephalic veins and one case of elastic recoil of
      the anastomotic site stenosis after PTA. Two patients were immediately lost on
      follow-up. The remaining 14 cases underwent successful hemodialysis 0 to 33 (mean
      = 15) days after PTA, showing 74% (14/19) clinical success. Although accessory
      branch veins were noted in most cases (74%, 14/19), leaving them alone did not
      affect the maturation of AVFs following PTA. There was no significant procedural
      or late complication. Primary and secondary patency rates at 1 year were 61 and
      82%, respectively. For those AVFs that failed to mature, there were stenoses
      along their vascular courses as underlying causes. For the percutaneous
      procedure, the retrograde transvenous approach was a reasonable one. As PTA is
      effective and quick for the salvation of immature AVFs, it can be considered a
      primary method for salvaging these immature AVFs.

PMID- 16001146
TI  - Effects of nitrate on the tadpoles of two Ranids (Rana catesbeiana and R.
      clamitans).
AB  - Nitrate is a potential stressor of amphibian larvae. Previous research has shown
      variation in the effects of nitrate among species and even populations of
      amphibians. However, relatively few species and populations of amphibians have
      been examined for nitrate tolerance, especially from populations in the
      agricultural regions of the United States. Using a 15-day laboratory experiment,
      we investigated the effects of nitrate on the larvae of two species of anurans
      (Rana catesbeiana and R. clamitans) that are common throughout the agricultural
      Midwest. Survival of R. catesbeiana and R. clamitans tadpoles was negatively
      affected by higher concentrations of nitrate (20 mg L(-1)), with R. clamitans
      being more affected than R. catesbeiana. The final mass of R. catesbeiana
      tadpoles was affected by nitrate concentration, with tadpoles exposed to
      intermediate concentrations of nitrate (5 mg L(-1)) being the heaviest. The final
      mass of R. clamitans tadpoles was not affected by nitrate concentration. These
      experiments suggest that these two species differ in their responses to the toxic
      effects of nitrate and, along with previous results on Ranids, suggest there is a
      great deal of variation in nitrate tolerance in this family.

PMID- 16001147
TI  - Use of skin and blood as nonlethal indicators of heavy metal contamination in
      northern water snakes (Nerodia sipedon).
AB  - Relatively little is known about contaminants in reptiles, particularly snakes.
      The concentrations of arsenic, cadmium, chromium, lead, manganese, mercury, and
      selenium were examined in blood and skin of 46 northern water snakes (Nerodia
      sipedon) in Tennessee and correlated with concentrations in internal tissues
      (liver, kidney, muscle) to determine if blood or skin could serve as a nonlethal
      indicator of internal metal exposure or body burden. Snakes were collected from
      the East Fork Poplar Creek (EFPC) within the United States Department of Energy's
      Y-12 National Security Complex (part of the Oak Ridge National Laboratory) and
      from a reference stretch of the Little River in East Tennessee. For blood, the
      only consistent positive correlations with internal organs were for mercury, and
      correlations were low except for muscle. Skin showed significant positive
      correlations with all three organs for mercury, chromium, selenium, and lead. For
      manganese and cadmium, skin level was positively correlated with liver level.
      Blood generally reflects recent exposure, not necessarily body burden, but in
      water snakes it correlates with body burden for mercury. Skin proved useful for
      more metals, although patterns were not necessarily consistent across sex and
      locality subgroups. The most consistent pattern was for mercury, the metal of
      greatest concern in many aquatic ecosystems, including EFPC.

PMID- 16001148
TI  - Bioaccumulation of PCBs in burbot (Lota lota L.) after delivery in natural food.
AB  - Burbot (Lota lota) caught from Lake Paijanne, Central Finland, were exposed under
      laboratory conditions to four polychlorinated biphenyl (PCB) congeners delivered
      through diet, and accumulation of congeners to muscle, intestine, gonads, and
      liver were determined. The selected PCB congeners (PCB18, PCB44, PCB137, and
      PCB169) were added to intact dead vendace (Coregonus albula) and burbot were fed
      5 or 10 contaminated meals (2- and 4-week experiment, respectively).
      Concentrations of fed congeners were different in the examined tissues. The
      highest concentrations of all the congeners were found in the livers of burbot.
      The mean retention efficiencies were 65.0% and 81.7% after 5 and 10 oral doses,
      respectively. The retention efficiency of the coplanar 169 was lower than those
      of the other fed congeners. The background organochlorine concentrations of the
      burbot of this study were compared with the PCB concentrations of burbot caught
      in the 1970s from Lake Paijanne. These concentrations were compared in order to
      clarify the PCB load and persistence in a boreal aquatic food web. The total PCB
      concentration in burbot has not declined during the last decades. The most
      abundant PCB congeners in the field were PCB138 and PCB153. Residual
      concentrations of pesticides were also found, especially the DDE, which is a
      metabolite of DDT.

PMID- 16001149
TI  - A short-term sublethal in situ sediment assay with Chironomus riparius based on
      postexposure feeding.
AB  - A short-term, sublethal, and cost-effective in situ sediment toxicity assay for
      routine assessments with the midge Chironomus riparius Meigen, based on
      postexposure feeding, was developed and evaluated. An inexpensive and easy-to-use
      assay chamber was designed. A sediment toxicity assay was successfully performed
      at a lentic system impacted by acid mine drainage, at sites with different types
      of sediment. It consisted of a 48-h exposure period followed by a 1-h
      postexposure feeding during which the larvae were fed on Artemia franciscana
      nauplii. Methodologies for feeding quantification of fourth-instar larvae (10-d
      old) were first developed and optimized under laboratory conditions. A.
      franciscana nauplii were shown to be more suited than fish flake food for
      postexposure feeding quantification, allowing higher precision and cost
      effectiveness. It also required a shorter postexposure feeding period, thus
      minimizing the chances for an eventual organism physiological recovery from
      toxicant exposure. The influence of several environmental conditions during
      exposure on postexposure feeding was also evaluated: temperature, dissolved
      oxygen, pH, salinity, hardness, substrate, humic acids, light, and food
      availability. Only temperature was found to significantly influence postexposure
      feeding rates; exposure at 5 degrees C led to reduced feeding activity compared
      to 30 degrees C. Recovery rates of 87% were obtained after the 48-h field
      exposure at all sites (except site R2). A statistically significant postexposure
      feeding depression was observed at the three sites impacted by acid mine
      drainage. Therefore, the proposed short-term in situ assay is a potentially
      useful tool to assess sediment sublethal toxicity on a routine basis.

PMID- 16001150
TI  - Evaluation of ionic contribution to the toxicity of a coal-mine effluent using
      Ceriodaphnia dubia.
AB  - The United States Environmental Protection Agency has defined national in-stream
      water-quality criteria (WQC) for 157 pollutants. No WQC to protect aquatic life
      exist for total dissolved solids (TDS). Some water-treatment processes (e.g., pH
      modifications) discharge wastewaters of potentially adverse TDS into freshwater
      systems. Strong correlations between specific conductivity, a TDS surrogate, and
      several biotic indices in a previous study suggested that TDS caused by a coal
      mine effluent was the primary stressor. Further acute and chronic testing in the
      current study with Ceriodaphnia dubia in laboratory-manipulated media indicated
      that the majority of the effluent toxicity could be attributed to the most
      abundant ions in the discharge, sodium (1952 mg/L) and/or sulfate (3672 mg/L),
      although the hardness of the effluent (792 +/- 43 mg/L as CaCO3) ameliorated some
      toxicity. Based on laboratory testing of several effluent-mimicking media, sodium
      and sulfate-dominated TDS was acutely toxic at approximately 7000 microS/cm
      (5143 mg TDS/L), and chronic toxicity occurred at approximately 3200 microS/cm
      (2331 mg TDS/L). At a lower hardness (88 mg/L as CaCO3), acute and chronic
      toxicity end-points were decreased to approximately 5000 microS/cm (3663 mg
      TDS/L) and approximately 2000 microS/cm (1443 mg TDS/L), respectively. Point
      source discharges causing in-stream TDS concentrations to exceed these levels may
      risk impairment to aquatic life.

PMID- 16001151
TI  - Effects of dietary administration of CL-20 on Japanese quail Coturnix coturnix
      japonica.
AB  - Hexanitrohexaazaisowurtzitane, or CL-20, is an emerging highly energetic compound
      currently under consideration for military applications. With the anticipated
      wide use of CL-20, there is the potential for soil and groundwater contamination
      resulting in adverse toxicologic effects on environmental receptors. Presently,
      there is a lack of data describing the toxic effects of CL-20 on avian species.
      The present study describes the effect of CL-20 on Japanese quail (Coturnix
      coturnix japonica) modified from standard toxicity test guidelines. First, a 14
      day subacute assay was adopted using repeated gavage doses (0, 307, 964, 2439,
      3475, or 5304 mg CL-20/kg body weight (BW)/d for 5 days followed by no CL-20
      exposure (vehicle only) for 10 days. Second, a subchronic feeding assay (0, 11,
      114, or 1085 mg CL-20/kg feed) was done for 42 days. During both studies, no
      overt toxicity was observed in the CL-20-treated birds. During the first 5 days
      of the subacute study, CL-20-exposed birds showed a dose-dependent decrease in BW
      gain, whereas increased liver weight, plasma sodium, and creatinine levels were
      observed in birds receiving the highest dose tested. For the subchronic study,
      embryo weights were significantly decreased in a dose-dependent manner. Embryos
      from CL-20-exposed birds were observed to have multiple cranial and facial
      deformities, beak curvatures, possible mid-brain enlargement, and classic one
      sided development with micro-opthalamia (nonstatistical comparisons with control
      embryos). A trend toward decreased number of eggs laid per female bird was also
      observed. We conclude that CL-20 (or its degradation products) elicits few
      effects in adults but may affect avian development, although these preliminary
      findings should be confirmed.

PMID- 16001153
TI  - Heavy metal concentrations in northern water snakes (Nerodia sipedon) from East
      Fork Poplar Creek and the Little River, East Tennessee, USA.
AB  - We compared the levels of arsenic, cadmium, chromium, lead, manganese, mercury,
      and selenium in the blood, kidney, liver, muscle, and skin of northern water
      snakes (Nerodia sipedon) collected from the upper reach of East Fork Poplar Creek
      (EFPC) within the United States Department of Energy's (USDOE's) Y-12 National
      Security Complex with concentrations in tissues of northern water snakes from a
      reference reach of the Little River downstream from the Great Smoky Mountains
      National Park in East Tennessee. Our objectives were to determine whether
      concentrations of these metals were higher in tissues of water snakes collected
      from EFPC compared with the reference site and if northern water snakes were
      suitable bioindicators of metal contamination. Except for chromium, metal levels
      were significantly higher in tissues (kidney, liver, muscle, and skin) of EFPC
      northern water snakes compared with those in tissues of snakes from the reference
      site. Although female northern water snakes were significantly larger than male
      snakes, their tissues did not contain significantly higher metal concentrations
      compared with those from male snakes, possibly because of maternal transfer of
      metals to eggs. This study was the first to examine the accumulation of
      contaminants resulting from the operations of the USDOE's Oak Ridge Reservation
      in snakes.

PMID- 16001154
TI  - Alterations of metabolic enzymes in Australian bass, Macquaria novemaculeata,
      after exposure to petroleum hydrocarbons.
AB  - Australian bass Macquaria novemaculeata were exposed to the water-accommodated
      fraction of Bass Strait crude oil, dispersed crude oil, or burnt crude oil to
      assess sublethal effects of oil spill remediation techniques on fish. Fish were
      exposed to these treatments for 16 days either through the water column or by way
      of a pre-exposed diet of amphipod Allorchestes compressa. Fish gills, liver, and
      white muscle were sampled and cytochrome C oxidase (CCO) and lactate
      dehydrogenase (LDH) activities quantified. In all treatments containing fish
      exposed by way of the water column, aerobic activity increased in the gills,
      whereas a decrease of this enzymic activity was observed in the liver and white
      muscle. Exposures by way of the food pathway indicated similar trends. Anaerobic
      (LDH) activity increased in the gills, liver, and white muscle after waterborne
      exposures. Stimulation in anaerobic activity also occurred in the liver and white
      muscle of fish after exposure to contaminated food. CCO activity in the gills was
      the most sensitive biomarker when monitoring waterborne exposures to petroleum
      hydrocarbons. In the gills, the dispersed oil treatment resulted in the most
      pronounced biological response, suggesting that in the short term the use of
      dispersants on an oil slick might cause the most perturbations to fish
      metabolism.

PMID- 16001155
TI  - Assessment of PCBs and PCDD/Fs along the Chinese Bohai Sea coastline using
      mollusks as bioindicators.
AB  - Mollusk samples such as bivalves and gastropods were collected from eight
      sampling sites along Bohai Sea coastline from northeastern China. The samples
      were analyzed for polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p
      dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) by high-resolution gas
      chromatography/high-resolution mass spectrometry (HRGC-HRMS) to elucidate
      bioaccumulation of persistent organic pollutants in benthon. Residue levels of
      sigmaPCBs and sigmaPCDD/Fs were in the ranges of 66.1 to 583.6 ng/g and 0.9 to
      15317 pg/g on a lipid-weight basis, respectively, The pollution source was
      identified using principal component analysis (PCA) in some coastal areas. It
      indicated that the typical pollution sources were characterized by PCB3, which
      was one Chinese technical product of PCBs. PCA also revealed the similarity
      patterns of PCBs between identical species collected from the different sites.
      The higher gastropod PCB concentrations were related to a former capacitor
      factory and the paint factories in some coastal areas, but this was not the case
      with the bivalves. The results of this study suggest that some gastropod species
      may be a potential bioindicator or "sentinel" organism for marine PCBs
      monitoring.

PMID- 16001156
TI  - Polychlorinated biphenyls and organochlorine pesticides in human adipose tissue
      and breast milk collected in Hong Kong.
AB  - Contamination from persistent organic pollutants is a pervasive global problem
      that urgently demands global concern and action. In the present study,
      concentrations of organochlorine (OC) pesticides and polychlorinated biphenyls
      (PCBs) were determined in 37 samples of female adipose tissue collected in Hong
      Kong hospitals. Among the pollutants analyzed, DDTs (2.79 ng/g fat), HCHs (0.72
      ng/g fat), and PCBs (0.19 ng/g fat) were prominent compounds in most of the
      adipose tissue. p,p'-DDE and hexachlorinated biphenyls were found in all samples,
      whereas heptachlor epoxide and dieldrin were found only in some samples. An
      estimation of toxic equivalency concentration (TEQ) due to dioxin-like coplanar
      PCBs was also performed. The estimated TEQ(PCBs) was 2.01 pg/g fat. This study
      also compared our previous results obtained from the milk samples of the same
      donors. Significant correlations are obtained for DDTs and HCHs between milk and
      adipose tissue. Detailed review of available information concerning OC pesticides
      and PCBs in different ecological compartments indicated that bioconcentration and
      biomagnification of these contaminants are common phenomena of the Pearl River
      Delta region, which has undergone rapid socioeconomic change in the past 20
      years. It is suggested to establish a regional organization in order to
      coordinate the monitoring of persistent organic pollutants in the region.

PMID- 16001157
TI  - Modulatory effect of cadmium exposure on deltamethrin-induced oxidative stress in
      Channa punctata Bloch.
AB  - The modulatory effect of cadmium pretreatment (0.2 mg/kg b.w. i.p.) on
      deltamethrin-induced oxidative stress and alterations of antioxidants was studied
      in freshwater fish Channa punctata Bloch. Lipid peroxidation (LPO) was measured
      as one of the indicators of oxidative stress. Activities of glutathione
      peroxidase, glutathione reductase, and glutathione-S-transferase were also
      studied in liver, kidney, and gills. Levels of reduced glutathione (GSH) were
      measured in various tissues. Fish pretreated with cadmium and subsequently
      exposed to deltamethrin showed significantly reduced LPO values when compared
      with deltamethrin-exposed fish. Conversely, in the kidney, a potentiation
      response was observed. Deltamethrin exposure in fish resulted in significant
      alteration in activities of glutathione-dependent antioxidant enzymes. In the
      cadmium preexposed fish, which were subsequently exposed to deltamethrin,
      antioxidant enzymes showed a tendency toward normalization over deltamethrin-only
      exposed fish in liver and gills. GSH also showed a similar pattern in liver and
      gills but in kidney it remained elevated. Cadmium alone had no significant effect
      on various parameters at the concentration used in this study. When
      metallothionein (MT) induction was studied, only liver showed an MT-like protein
      band in sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis. These
      results demonstrate a modulatory role of cadmium on the oxidative stress and
      other related parameters in liver and gills. These findings are important in the
      context of exposure to a mixture of pollutants in aquatic environment.

PMID- 16001158
TI  - Two cases of cystic seroma following mesh incisional hernia repair.
AB  - Cystic seromas, or mature fibrous cysts, are rare complications after ventral and
      incisional hernioplasties employing polypropylene mesh. We analyzed the medical
      records of patients, whose abdominal-wall hernias were surgically repaired with
      polypropylene mesh from November 1996 to February 2004 (N=685). Of the 162
      patients, who had incisional hernias repaired with the Rives technique
      (preperitoneal mesh), we detected two patients who developed giant cystic
      seromas. Both patients underwent surgical resection of the cyst wall. As follow
      up care improves for patients undergoing hernioplasties with polypropylene
      meshes, more cystic seromas are detected, thereby improving our knowledge of the
      clinical, radiological, and histopathological characteristics of this
      complication. However, the etiologic factors related to the appearance of this
      chronic cyst remain uncertain.

PMID- 16001159
TI  - Primacy, pell-mell paternity...praises and perils.

PMID- 16001160
TI  - Hernia repair: 2005. A reflection.

PMID- 16001162
TI  - Immunotherapy in chronic lymphocytic leukemia.

PMID- 16001161
TI  - Immunotherapeutic potential of DISC-HSV and OX40L in cancer.
AB  - Several vectors, viral and bacterial, have been developed over the past few years
      for means of generating an effective antitumor immune response. We have developed
      and studied a "model for immunotherapy" using a viral vector disabled infectious
      single cycle-herpes simplex virus (DISC-HSV), which efficiently transduces
      various tumor cell lines and offers a useful vehicle for the further development
      of cell-based vaccines. The immunotherapeutic potential of DISC-HSV encoding
      granulocyte macrophage colony stimulating factor (GM-CSF) was demonstrated in a
      number of murine carcinoma models, leading to complete regression of well
      established tumors in up to 70% of the mice. Moreover, the therapeutic potential
      of DISC-HSV-GM-CSF was significantly enhanced when used in combination therapy
      with either OX40L or dendritic cells (DC), even in a poorly immunogenic tumor
      model. The ability of this vector to accept large gene inserts, its good safety
      profile, its ability to undergo only a single round of infection, the inherent
      viral immunostimulatory properties and its ability to infect various tumor cell
      lines efficiently, make DISC-HSV an ideal candidate vector for immunotherapy. The
      DISC- CT-26 tumor model was used to investigate the mechanisms associated with
      immunotherapy induced tumor rejection. Although CTL induction, was positively
      correlated with regression, MHC class I down regulation and accumulation of
      immature Gr1+ myeloid cells were shown to be the main immuno-suppressor
      mechanisms operating against regression and associated with progressive tumor
      growth. The CTL response was associated with the immuno-dominant AH-1 peptide of
      the retroviral glycoprotein gp70. This model of immunotherapy has provided an
      opportunity to dissect further the immunological events associated with tumor
      rejection and escape. Since other antigens may be important in initiating tumor
      rejection, we have investigated the expression of MTA-1, an antigen that appears
      to be expressed widely in human and murine tumors. The immunogenicity of MTA-1
      was studied and its potential as a tumor rejection antigen is under
      investigation.

PMID- 16001163
TI  - Identification of identical TCRs in primary melanoma lesions and tumor free
      corresponding sentinel lymph nodes.
AB  - It is generally believed that priming of efficient T-cell responses takes place
      in peripheral lymphoid tissues. Although this notion has been rigidly proven for
      infectious diseases, direct evidence for lymph node priming of in vivo T-cell
      responses against tumors is still lacking. In the present study, we conducted a
      full and nonbiased comparison of T-cell clonotypes in melanoma lesions and
      corresponding sentinel lymph nodes. Whereas most tumor lesions comprised a high
      number of T-cell clonotypes, only a small number of clonally expanded T cells
      were detected in the draining lymph nodes. Comparative clonotype mapping
      demonstrated the presence of identical T-cell clonotypes in the tumors and the
      respective sentinel lymph nodes, only when tumor cells were present in the
      latter. However, taking advantage of clonotype specific PCR amplification, TCR
      sequences representing clonally expanded T cells at the tumor site could be
      detected in the lymph nodes draining the tumors even in the absence of tumor
      cells. Evidence for the tumor-specific characteristics of these cells was
      obtained by in situ staining with peptide/HLA class I complexes demonstrating the
      presence of MART-1/HLA-A2- and MAGE-3/HLA-A2-reactive T cells at the tumor site,
      as well as in the draining lymph node. Our data indicate that T-cell responses to
      melanoma are primed in the sentinel lymph node by cross presentation of tumor
      antigens by dendritic cells.

PMID- 16001164
TI  - Adenoviral-mediated transfer of human wild-type p53, GM-CSF and B7-1 genes
      results in growth suppression and autologous anti-tumor cytotoxicity of multiple
      myeloma cells in vitro.
AB  - Multiple myeloma (MM) remains incurable despite the use of high-dose chemotherapy
      and stem cell transplantation. However, immunotherapy is expected to offer long
      term disease control, or even possibly a cure. We have previously demonstrated
      the suppressive effect of a recombinant adenovirus carrying human wild-type p53,
      granulocyte-macrophage colony-stimulating factor, and B7-1 genes (Ad-p53/GM
      CSF/B7-1) on the growth of laryngeal cancer cells. In the present study, we
      evaluated the effects of an Ad-p53/GM-CSF/B7-1-modified myeloma cell vaccine
      strategy aimed to induce apoptosis and to augment the immunogenicity of MM cells.
      Both MM cell lines and purified primary myeloma cells were infected with Ad
      p53/GM-CSF/B7-1. High expression levels of these three genes were confirmed
      separately by Western blot, enzyme-linked immunosorbent assay (ELISA), and flow
      cytometry. When wild-type p53, GM-CSF and B7-1 genes were introduced, the growth
      of MM cells was inhibited via enhanced apoptosis and the immunogenicity of tumor
      cells was augmented. The combinatorial effect of these three genes on inducing
      cytotoxic T lymphocytes (CTLs) was more evident than that of p53 individually or
      any combinations of two (p53 plus GM-CSF or p53 plus B7-1). Furthermore,
      significant proliferation of autologous peripheral blood lymphocytes (PBLs) and
      specific cytotoxicity against autologous primary MM cells were induced in vitro.
      These results suggest that myeloma cell vaccination co-transferred with p53, GM
      CSF and B7-1 genes may be a promising immunotherapeutic approach against MM.

PMID- 16001165
TI  - The absolute bioavailability of oral vinorelbine in patients with solid tumors.
AB  - Due to advances in the methods used to quantitate vinorelbine, this study was
      conducted to characterize fully the bioavailability of an oral dosage form of
      vinorelbine. Twenty-seven eligible patients with solid tumors were enrolled onto
      this study and were treated in a randomized crossover design to receive either 70
      mg/m2 orally or 30 mg/m2 intravenously followed by the alternative treatment one
      week later. Vinorelbine was administered orally as a soft-gelatin capsule.
      Pharmacokinetic sampling was carried out for 7 days following each dose. Whole
      blood vinorelbine concentrations were measured using a sensitive LC/MS/MS method.
      The data from patients were excluded if they vomited within 3 h after the oral
      dose. RESULTS: Three subjects were removed from study following the first dose
      due to safety reasons. Of the remaining 24 subjects, five experienced vomiting
      within 3 h of oral dosing. Total body clearance calculated from the intravenous
      dose was 43.65 L/h (+/-10.9) and the terminal half-life was estimated to be 49 h.
      Using complete data from the remaining 19 subjects, the mean absolute
      bioavailability of the oral dosage formulation of vinorelbine was calculated to
      be 33% (+/-18%). In conclusion we have characterized the pharmacokinetics of both
      orally administered and intravenous vinorelbine over 7 days after administration
      and have determined the mean oral bioavailability of this oral formulation to be
      33%.

PMID- 16001166
TI  - Enhancing the therapeutic responsiveness of photodynamic therapy with the
      antiangiogenic agents SU5416 and SU6668 in murine nasopharyngeal carcinoma
      models.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality using
      a tumor localizing photosensitizer and light to destroy tumor cells. A major
      limitation of PDT is tumor recurrence, which is partly due to neovascularization.
      PURPOSE: The objective of the present study was to determine whether combination
      therapy with PDT and antiangiogenic agents (i.e. SU5416 and SU6668) would be more
      effective in controlling tumor recurrence in a mouse model of human CNE2 poorly
      differentiated nasopharyngeal carcinoma compared with PDT or antiangiogenic
      agents administered alone. METHODS: Athymic mice bearing CNE2 tumor xenografts
      received daily i.p. injections of 20 mg/kg SU5416 or 100 mg/kg SU6668 for 28
      consecutive days either alone or following a single hypericin-PDT treatment.
      RESULTS: Significant inhibition of CNE2 tumor growth was observed in all
      treatment groups. Differences in 4x tumor growth time, the number of mice with 4x
      tumor growth, tumor growth inhibition as well as the percent of mice surviving
      were not statistically significant among individual treatment groups. However,
      the number of mice with 4x tumor growth observed in SU6668 monotherapy and
      combined PDT and SU6668 treatment groups was significantly less than that in the
      control group (P<0.05 and 0.01, respectively). Moreover, compared with the
      control group, only the combined PDT and SU6668 treatment significantly extended
      survival of tumor-bearing host mice (P<0.05). The semiquantitative RT-PCR results
      showed that the expression of HIF-1alpha, VEGF, COX-2 and bFGF were increased in
      PDT-treated tumor samples collected 24 h post-PDT, suggesting that PDT-induced
      damage to tumor microvasculature and the resultant hypoxia upregulate the
      expression of certain proangiogenic factors. CONCLUSIONS: The effectiveness of
      PDT can be enhanced by antiangiogenic treatment with the synthetic RTK
      inhibitors. Of the two synthetic RTK inhibitors tested, SU6668 was more effective
      than SU5416 in enhancing tumor responsiveness to PDT.

PMID- 16001167
TI  - Camptothecin analogs with enhanced activity against human breast cancer cells.
      II. Impact of the tumor pH gradient.
AB  - Human breast tumors often exist in an acidic and hypoxic microenvironment, which
      can promote resistance to radiation and chemotherapies. A tumor-selective pH
      gradient arises in these tumors which favors uptake and retention of drugs like
      camptothecin that are weak acids. We evaluated the effect of alkyl substitutions
      at the 7 position in seven CPTs with varying groups at the 10 position on
      modulation by acidic extracellular pH in three human breast cancer cell lines.
      Growth inhibition was assessed by propidium iodide staining of nucleic acids in
      human breast cancer cells cultured at either extracellular pH 6.8 or 7.4 that
      were (1) hormone-sensitive (MCF-7/wt), (2) hormone insensitive (MDA-MB-231), or
      (3) alkylator-resistant (MCF-7/4-hc). Over 10-fold pH modulation was observed in
      7-halomethyl analogs of methylenedioxy-CPT and in 7-alkyl analogs of 10-amino
      CPT. Of 39 analogs tested, the overall pattern of activity across breast tumor
      cell lines was similar with some notable exceptions. For example, 7-propyl-10
      amino-CPT was modulated 16- to 20-fold by acidic extracellular pH in the MCF-7
      cell lines, but only 6-fold in MDA-MB-231 cells. One mechanism that can
      contribute to pH modulation is enhanced cellular drug uptake and retention. In
      MCF-7/wt cells, uptake of 10-amino-CPT increased 4-fold, while retention
      increased over 10-fold at acidic extracellular pH. In addition, gene expression
      analysis of MCF-7/wt cells indicated that expression of a number of genes changed
      under acidic culture conditions, including down-regulation of the CPT efflux
      protein pump breast cancer resistance protein (BCRP). Interestingly, expression
      of topoisomerase I, the molecular target of CPT, was not affected by acidic
      growth conditions. These results highlight the importance of maintaining key
      features of tumor physiology in cell culture models used to study cancer biology
      and to discover and develop new anticancer drugs. While several substitutions at
      the 7 and 10 positions enhance potency, 7-halomethyl and 10-amino CPT analogs
      show selective activity at the acidic pH common to the microenvironment of most
      solid tumors.

PMID- 16001168
TI  - Schedule-dependent interaction between Doxorubicin and mTHPC-mediated
      photodynamic therapy in murine hepatoma in vitro and in vivo.
AB  - PURPOSE: To evaluate cytotoxic and antitumor effects of a conventional anticancer
      drug Doxorubicin (Dox) and photodynamic therapy (PDT) mediated by a promising
      photosensitizer of second generation meta-tetra (3-hydroxyphenyl)-chlorin (mTHPC)
      in combination. METHODS: Murine hepatoma MH-22A was used for investigation in
      vitro and in vivo. In vitro, the cells were incubated with 0.15 microg/ml mTHPC
      for 18 h and exposed to light from LED array (lambda = 660+/-20 nm) at 0.6-2.4
      kJ/m2. 0.05-0.2 microg/ml Dox was administered either 24 h prior to or
      immediately after light exposure (Dox-->PDT or PDT + Dox, respectively). The
      cytotoxicity was tested by staining with crystal violet. The character of the
      combined effect was assessed by multiple regression analysis. In vivo, the
      antitumor activity was estimated by monitoring the tumor volume over time, in
      mice transplanted subcutaneously with MH-22A and treated with Dox and/or PDT. For
      PDT, mice were exposed to light from diode laser (lambda = 650+/-2 nm) at 12
      kJ/m2 following 24 h after administration of 0.15 mg/kg mTHPC. A 3 mg/kg Dox was
      administered either within 15 min prior to mTHPC or within 15 min after light
      exposure (Dox-->PDT or PDT + Dox, respectively). RESULTS: Both in vitro and in
      vivo, the combination of mTHPC-mediated PDT and Dox was evaluated to be more
      effective than each treatment alone. In vitro, the difference between cell
      viability curves after photodynamic treatment as a single modality and after
      combination of photodynamic treatment with Dox was statistically significant
      under most of the applied conditions (P < or = 0.02). In the case of PDT + Dox,
      the combination had an additive character, and the sequence Dox-->PDT caused a
      sub-additive interaction. In vivo, both regimens of combination were more
      effective in inhibiting tumor growth than any single treatment (P < 0.09). The
      antitumor activity of PDT + Dox regimen was more prominent than that of Dox-
      >PDT; however, significance of the difference was not high (P = 0.08).
      CONCLUSIONS: These results indicate that Dox potentiates therapeutic efficacy of
      mTHPC-mediated PDT and vice versa, and the degree of potentiation is influenced
      by the combination schedule: administration of Dox immediately after light
      exposure is preferable to administration of Dox at 24 h prior to light exposure.

PMID- 16001169
TI  - Bcl-2-mediated potentiation of neocarzinostatin-induced apoptosis: requirement
      for caspase-3, sulfhydryl groups, and cleavable Bcl-2.
AB  - Overexpression of antiapoptotic Bcl-2 family members is thought to contribute to
      chemotherapeutic resistance of neural crest tumors. Paradoxical potentiation by
      Bcl-2 of apoptosis induced by the antineoplastic prodrug, neocarzinostatin (NCS),
      has been observed in PC12 pheochromocytoma cells. Prior studies have indicated
      that the cleavage of Bcl-2 to its proapoptotic counterpart mediated by caspase-3
      is responsible for this potentiation of apoptosis. This has led to the hypothesis
      that induction of caspase-3 expression in bcl-2-transfected, caspase-3-deficient
      MCF-7 cells, will result in Bcl-2 cleavage and Bcl-2-dependent potentiation of
      NCS-induced apoptosis. These studies have further led to the hypothesis that both
      cleavable Bcl-2 and sulfhydryl groups are required for the activity of caspase-3
      in this regard. As hypothesized, co-transfection of bcl-2-transfected MCF-7 cells
      with a caspase-3 expression construct results in cleavage of Bcl-2 and
      potentiation of dose-dependent, NCS-mediated cell death. Furthermore, PC12 cells
      transfected with an expression construct for cleavage-resistant Bcl-2
      demonstrated attenuated potentiation of apoptosis relative to their counterparts
      transfected with wild-type bcl-2. Finally, irreversible oxidative titration of
      sulfhydryl groups resulted in concentration-dependent attenuation of apoptosis in
      PC12 cells, along with prevention of caspase-3 activation and Bcl-2 cleavage.
      These results definitively demonstrate the requirement for caspase-3, cleavable
      Bcl-2, and available sulfhydryl groups (separate from those required for NCS
      activation) in potentiation of NCS-induced apoptosis by Bcl-2.

PMID- 16001170
TI  - Effect of amifostine on the cytotoxicity of daunorubicin and daunoxome in tumor
      and normal cells.
AB  - Anthracyclines are powerful cytotoxic agents, used as first-line treatment of
      leukemias and many other tumors, but host-tissue toxicity is their main dose
      limiting factor. However, their therapeutic effects depend not only on the
      toxicity, hence on the dose, but also on drug resistance. Among the mechanisms
      that can account for cell sensitivity to anthracyclines, there is an
      overexpression of drug transport proteins, like the transmembrane P-glycoprotein
      (PGP), the multidrug- resistance-related protein (MRP) and the lung-resistance
      related protein (LRP). Attempts to reduce the toxicity of chemotherapeutic agents
      without affecting their efficacy have been made using liposomal anthracyclines or
      cytoprotective agents, as Amifostine. The aim of this study was to evaluate and
      compare the toxic effects of Daunorubicin, in normal or liposomal formulation,
      used in combination with WR1065, the active metabolite of Amifostine, against
      normal and tumor cells. In conclusion these data show that the preincubation with
      WR-1065 does not inhibit the drug toxic effect on blast cells and on tumor cell
      lines, independently by their multidrug resistance phenotype, but has a
      cytoprotective effect on stem cells causing a drug cytotoxicity reduction of 10
      20%. This advantage is even higher using the liposomal formulation of DNR.
      Therefore, Amifostine can offer a chance of protecting normal cells from the
      toxicity of anthracyclines, in normal or liposomal formulation. The combination
      of liposomal anthracyclines with Amifostine can confer further advantages in
      management of leukemic patients, especially the elderly where treatment toxicity
      is a main problem. These patients may be candidates for alternative therapeutic
      strategies and the combination of DNX and Amifostine is an attractive treatment
      for these cases where a low nonhematological toxicity is required.

PMID- 16001171
TI  - Preliminary safety evaluation of the putative cancer chemopreventive agent
      tricin, a naturally occurring flavone.
AB  - PURPOSE: Naturally occurring flavonoids such as quercetin and genistein possess
      cancer chemopreventive properties in experimental models. However, adverse
      effects such as their mutagenicity confound their potential clinical usefulness.
      Furthermore in leukaemia cells some flavonoids cleave the breakpoint cluster
      region of the mixed lineage leukaemia (MLL) gene as a consequence of inhibition
      of topoisomerase II. The choice of flavonoids to be developed as cancer
      chemopreventive agents depends crucially on their safety. Here, we explored
      safety aspects of the novel flavone tricin, a constituent of rice bran and other
      grass species, which has recently been found to interfere with murine
      gastrointestinal carcinogenesis. METHODS: Evidence of pathological or
      morphological changes in liver, lung, heart, spleen, kidney, adrenal gland,
      pancreas or thymus tissues was studied in mice which received tricin, genistein
      or quercetin 1,000 mg/kg daily by the oral route on five consecutive days. The
      ability of tricin (50 microM) to cleave the MLL gene was studied in human
      leukaemia cells by Southern blotting, and its effect on human topoisomerase II
      activity was investigated in incubations with supercoiled DNA. The mutagenicity
      of tricin was assessed in the Salmonella/Escherichia coli assay, and its
      clastogenicity was adjudged by chromosomal aberrations in Chinese hamster ovary
      cells and occurrence of micronuclei in bone marrow erythrocytes in Swiss-Webster
      mice. RESULTS: Neither tricin, quercetin, or genistein caused pathological or
      morphological changes in any of the murine tissues studied. Tricin (50 microM)
      failed to cause MLL gene breakage, and it inhibited topoisomerase II only at 500
      microM, but not at 10, 50 or 100 microM. Tricin lacked genotoxic properties in
      the systems studied here. CONCLUSION: The results tentatively suggest that tricin
      may be considered safe enough for clinical development as a cancer
      chemopreventive agent.

PMID- 16001172
TI  - Imaging the pharmacokinetics of [F-18]FAU in patients with tumors: PET studies.
AB  - PURPOSE: FAU (1-(2'-deoxy-2'-fluoro-beta-D: -arabinofuranosyl) uracil) can be
      phosphorylated by thymidine kinase, methylated by thymidylate synthase, followed
      by DNA incorporation and thus functions as a DNA synthesis inhibitor. This first
      in-human study of [F-18]FAU was conducted in cancer patients to determine its
      suitability for imaging and also to understand its pharmacokinetics as a
      potential antineoplastic agent. METHODS: Six patients with colorectal (n = 3) or
      breast cancer (n = 3) were imaged with [F-18]FAU. Serial blood and urine samples
      were analyzed using HPLC to determine the clearance and metabolites. RESULTS:
      Imaging showed that [F-18]FAU was concentrated in breast tumors and a lymph node
      metastasis (tumor-to-normal-breast-tissue-ratio 3.7-4.7). FAU retention in breast
      tumors was significantly higher than in normal breast tissues at 60 min and
      retained in tumor over 2.5 h post-injection. FAU was not retained above
      background in colorectal tumors. Increased activity was seen in the kidney and
      urinary bladder due to excretion. Decreased activity was seen in the bone marrow
      with a mean SUV 0.6. Over 95% of activity in the blood and urine was present as
      intact [F-18]FAU at the end of the study. CONCLUSIONS: Increased [F-18]FAU
      retention was shown in the breast tumors but not in colorectal tumors. The
      increased retention of FAU in the breast compared to bone marrow indicates that
      FAU may be useful as an unlabeled antineoplastic agent. The low retention in the
      marrow indicates that unlabeled FAU might lead to little marrow toxicity;
      however, the images were not of high contrast to consider FAU for diagnostic
      clinical imaging.

PMID- 16001173
TI  - Bi-weekly chemotherapy with cisplatin, epirubicin, folinic acid and 5-fluororacil
      continuous infusion plus g-csf in advanced gastric cancer: a multicentric phase
      II study.
AB  - BACKGROUND: It has been demonstrated that the 3-weekly PELF regimen is superior
      to FAM and FAMTX in advanced gastric cancer. The aim of this multicentric phase
      II study was to evaluate the efficacy and tolerability of a PELF regimen, given
      every 2 weeks as a first-line therapy in patients with unresectable or metastatic
      gastric carcinoma. METHODS: Fifty-nine patients were treated with the following
      schedule: cisplatin (40 mg/m2, day 1), epirubicin (30 mg/m2, day 1), 5
      fluorouracil (400 mg/m2 bolus, followed by 600 mg/m2, 22 h continuous infusion,
      day 1 and 2) and folinic acid (100 mg/m2, 2-h infusion, day 1 and 2). G-CSF (5
      microg/kg) was administered on day 6, 8, 10, and 12. Cycles were repeated every 2
      weeks for a maximum of twelve courses. RESULTS: Of the 52 evaluable patients,
      three (5.8%) complete responses, and 15 (28.8%) partial responses were observed,
      for an overall response rate of 34.6%. The median duration of response was 8
      months. Nineteen patients had stable disease and 15 progressed on therapy. At a
      median follow-up of 12 months, the median time to progression was 8 months and
      the median survival duration was 13 months, with a 1-year survival rate of 53.5%.
      Grade 3 or 4 observed toxicities were: neutropenia in 26 patients (44%),
      thrombocytopenia in four patients (6.7%), and mucositis in seven patients
      (11.9%). CONCLUSIONS: The bi-weekly PELF regimen seems to be feasible with an
      acceptable toxicity profile and an activity comparable to the 3-weekly schedule.

PMID- 16001174
TI  - Phase I study of the combination of topotecan and irinotecan in children with
      refractory solid tumors.
AB  - PURPOSE: We have shown in xenograft studies that the antitumor activities of
      topotecan and irinotecan are highly schedule- and dose-dependent, with a high
      frequency of response at low, protracted dose schedules. Preclinical and clinical
      data suggest that topotecan and irinotecan have different antitumor activities
      and mechanisms of resistance, and non-overlapping toxicities, providing a
      rationale for their combination. Combining both agents may increase the amount of
      camptothecin delivered to the tumor, without additive toxicity. METHODS: We
      conducted a phase I study in children with refractory solid tumors to determine
      the maximum tolerated dose (MTD) of irinotecan when administered with a targeted
      systemic exposure (TSE) of topotecan and to define the dose-limiting toxicity
      (DLT) of this combination. Irinotecan was administered IV over 60 min followed by
      topotecan over 30 min daily for 5 days for two consecutive weeks. We initially
      fixed the topotecan-TSE to 80+/-10 ng*h/ml and investigated the ability to
      escalate irinotecan (starting dose 16 mg/m2/d). Topotecan and irinotecan
      pharmacokinetics were determined. RESULTS: Eleven patients (median age 10 years)
      were enrolled. Owing to DLT, irinotecan was de-escalated to 12 (level -1; n = 3)
      and 9 (level -2; n = 3) mg/m2/day, and topotecan-TSE was reduced to 60+/-10
      ng*h/ml (level -3; n = 2). DLTs were neutropenia (n = 8), typhlitis (n = 5), and
      skin rash (n = 1). MTD could not be reached. Median (range) irinotecan and
      topotecan lactone systemic clearances were 50.3 (16.6-76.2) l/h/m2 and 27.6 (14.7
      55.9) l/h/m2, respectively. The pharmacokinetics profile of each agent was
      similar to that seen in previous single agent studies. One patient with
      neuroblastoma and one with rhabdomyosarcoma had a partial and a complete
      response, respectively. CONCLUSION: Despite promising antitumor activity, the
      combination of topotecan and irinotecan given on a protracted schedule does not
      warrant further development in children due to unacceptable toxicity.

PMID- 16001175
TI  - Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate
      cancer patients.
AB  - OBJECTIVES: To investigate the safety and efficacy of docetaxel and zoledronic
      acid in patients with hormone-refractory prostate cancer (HRPC), based on
      preclinical evidence of synergism between taxanes and bisphosphonates. METHODS:
      Twenty-five patients with advanced HRPC received weekly docetaxel 30 mg/m2: in 18
      patients with symptomatic bone metastases and normal renal function, docetaxel
      was combined with zoledronic acid, 4 mg i.v. every 4 weeks. Premedication
      consisted of intravenous dexamethasone before docetaxel. No oral steroids were
      given. RESULTS: Overall, 12 patients (48%) had a PSA response (reduction of 50%
      or more compared to baseline). A PSA response was achieved in 8/18 patients (44%)
      receiving concomitant docetaxel and zoledronic acid, and in 7/12 patients (58%)
      receiving docetaxel and zoledronic acid as first-line therapy. The weekly
      schedule of docetaxel resulted in a mean received dose intensity of 26
      mg/m2/week, or 87% of the planned dose intensity. Toxicity was mild and as
      expected for docetaxel. The median time to progression was 7 months, and the
      median overall survival was 16 months. CONCLUSIONS: Concomitant treatment with
      docetaxel and zoledronic acid is safe and has encouraging activity in HRPC. The
      combination should be evaluated in randomised clinical trials.

PMID- 16001176
TI  - Treatment of anthracycline extravasation in mice with dexrazoxane with or without
      DMSO and hydrocortisone.
AB  - Dexrazoxane has been reported to be protective against anthracycline induced
      subcutaneous ulceration in mice. It is currently under clinical investigation as
      an acute antidote in accidental anthracycline extravasation, for which indication
      topical dimethylsulfoxide (DMSO) and intralesional hydrocortisone are used
      empirically. We studied the effect in 72 mice of monotherapy with and combined
      therapy of intraperitoneal dexrazoxane, topical DMSO, and intralesional
      hydrocortisone as acute antidotes against ulceration after subcutaneous
      daunorubicin. Dexrazoxane completely prevented wounds from occurring, while
      neither DMSO nor hydrocortisone had any preventive effect. The addition of
      topical DMSO actually reduced the efficacy of dexrazoxane. In conclusion, the
      present study does not support the concomitant use of topical DMSO + systemic
      dexrazoxane or intralesional hydrocortisone + systemic dexrazoxane. Monotherapy
      with systemic dexrazoxane seems preferable and is highly efficacious in
      preventing ulceration.

PMID- 16001177
TI  - Feasibility study of ambulatory continuous infusion of 5-fluorouracil followed by
      cisplatin through hepatic artery for metastatic colorectal cancer.
AB  - PURPOSE: A great synergy has been reported in a number of preclinical studies
      when 5-fluorouracil (5-FU) precedes cisplatin (CDDP). The objective of this study
      was to determine the feasibility of ambulatory continuous infusion of 5-FU
      followed by CDDP through hepatic artery for metastatic colorectal cancer.
      PATIENTS AND METHODS: Seventeen patients with unresectable liver metastases, who
      underwent primary tumor resection, were treated with 5-FU (450 mg/m2/day) for
      seven consecutive days followed by CDDP (100 mg/body/week) for seven consecutive
      days, each administered continuously by using a balloon pump via Infuse-A-Port
      catheter inserted into common hepatic artery. The doses of drugs were reduced 20%
      in patients older than 70 years. The treatment was repeated every 4-6 weeks until
      disease progression. RESULTS: Of 17 assessable patients, nine patients showed PR
      (53%; 95% CI, 29.3-76.7%) and eight patients had SD (47%; 95% CI, 23.3-70.7%),
      with disease control rate of 100%. The median overall survival was 26 months (95%
      CI: 17.5-41 months) and TTP 14 months (95% CI: 11-20.3 months). Two patients
      (11.8%), who showed progression due to collateral feeding arteries, responded to
      HAI again after occlusion. Grade 3 toxicity included leukopenia (12%) and anemia
      (24%). Grade 4 toxicity was absent. Four patients (23.5%) progressed at
      extrahepatic sites. CONCLUSIONS: This sequential combination of 5-FU followed by
      CDDP through hepatic artery is active and safe in an outpatient setting, and
      warrants further multi-institutional study, although prevention of
      micrometastasis would be mandatory to further prolong overall survival.

PMID- 16001178
TI  - Mild skin photosensitivity in cancer patients following injection of Photochlor
      (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a; HPPH) for photodynamic
      therapy.
AB  - PURPOSE: To measure skin photosensitivity in cancer patients infused with the new
      second-generation photodynamic sensitizer Photochlor (2-[1-hexyloxyethyl]-2
      devinyl pyropheophorbide-a). A major disadvantage of using the clinically
      approved photosensitizer Photofrin is potentially prolonged and sometimes severe
      cutaneous phototoxicity. PATIENTS AND METHODS: Forty-eight patients enrolled in
      Phases 1 and 2 clinical trials underwent two or more exposures to four graded
      doses (44.4, 66.6, 88.8 or 133.2 J/cm2) of artificial solar-spectrum light (SSL)
      before and after administration of Photochlor at a dose of 2.5, 3, 4, 5 or 6
      mg/m2 . RESULTS: The most severe skin response, experienced by only six of the
      subjects, was limited to erythema without edema and could only be elicited by
      exposure to the highest light dose. Conversely, eight subjects had no discernible
      reaction to SSL at any light dose. For nearly all the patients, the peak skin
      response was obtained when the interval between sensitizer injection and exposure
      to SSL was 1 day and, generally, their sensitivity to SSL decreased with
      increasing sensitizer-light interval. For example, a 2-day sensitizer-SSL
      interval resulted in less severe reactions than those obtained with the 1-day
      interval in 79% of the subjects, while 90% of the subjects exposed to SSL 3 days
      after Photochlor infusion had responses that were less severe than those obtained
      with either the 1- or 2-day sensitizer-SSL interval. CONCLUSIONS: Photochlor, at
      clinically effective antitumor doses, causes only mild skin photosensitivity that
      declines rapidly over a few days.

PMID- 16001179
TI  - Aplidin reduces growth of anaplastic thyroid cancer xenografts and the expression
      of several angiogenic genes.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive and
      highly lethal human cancers. Median survival after diagnosis is 4-6 months
      despite available radiotherapy and chemotherapy. Additional treatments are needed
      for ATC. Vascular endothelial growth factor (VEGF) is a potent angiogenic
      stimulus, which is expressed by ATC. Previously, anti-VEGF antibody was used to
      block VEGF-dependent angiogenesis in ATC xenografts. This treatment induced
      partial (56%) but not complete tumor regression. Aplidin (APLD) is a marine
      derived antitumor agent currently in phase II clinical studies. Multiple
      activities of this compound have been described which likely contribute to its
      antiproliferative effect. Notably, APLD has been shown to have antiangiogenic
      properties which include: inhibition of VEGF secretion, reduction in the
      synthesis of the VEGF receptor (FLT-1), and blockade of matrix metalloproteinase
      production by endothelial cells. We hypothesized that Aplidin, with its broad
      spectrum of action and antiangiogenic properties, would be a potentially
      effective drug against ATC. METHODS: Thirty BALB/c nu/nu mice were injected with
      ATC cells (ARO-81, 1 x 10(6)) and allowed to implant for 3 weeks. Animals were
      randomized to receive daily intraperitoneal injections of vehicle, low dose (0.5
      mg/kg/day), or high dose (1.0 mg/kg/day) APLD. After 3 days, the animals were
      killed and the tumors were removed, weighed, and divided for RNA and protein
      analyses. RESULTS: APLD significantly reduced ATC xenograft growth (low dose, 20%
      reduction, P = 0.01; high dose, 40% reduction, P < 0.001). This was associated
      with increased levels of apoptosis related proteins polyadenosylribose polymerase
      85 (PARP-85, 75% increase, P = 0.024) and caspase 8 (greater than fivefold
      increase, P = 0.03). APLD treatment was further associated with lost or reduced
      expression of several genes that support angiogenesis to include: VEGF, hypoxia
      inducible factor 1(HIF-1), transforming growth factor-beta (TGFbeta), TGFbeta
      receptor 2 (TGFbetaR2), melanoma growth stimulating factor 1 (GRO1), cadherin,
      and vasostatin. CONCLUSIONS: This data supports the hypothesis that APLD may be
      an effective adjunctive therapy against ATC. The demonstrated molecular impact
      against angiogenic related genes specifically supports future strategies
      combining APLD with VEGF interacting agents.

PMID- 16001180
TI  - Comparison of modern marker proteins in serum and synovial fluid in patients with
      advanced osteoarthrosis and rheumatoid arthritis.
AB  - Numerous studies have focused on the significance of modern marker proteins in
      the synovial fluid of the knee joint and in the serum both, for osteoarthritis
      (OA) and rheumatoid arthritis (RA). The relationship between the serum
      concentrations and the concentrations in the synovial fluid is still unclear.
      Synovial fluid and serum samples were obtained from 13 patients with advanced OA
      and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13,
      TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against
      the total protein concentrations. Serum concentrations of MMP-13 in the RA-group
      were statistically higher than the synovial values (P<0.05). MMP-13 was the only
      marker protein that revealed distinct higher levels in the serum than in the
      synovial fluid. The study design allows only conclusions about advanced stages of
      RA and OA. Longitudinal investigations may provide further information about the
      value of MMP-13 as a potential marker to monitor the course of RA and OA.

PMID- 16001182
TI  - Effects of global electrosensory signals on motion processing in the midbrain of
      Eigenmannia.
AB  - Wave-type weakly electric fish such as Eigenmannia produce continuous sinusoidal
      electric fields. When conspecifics are in close proximity, interaction of these
      electric fields can produce deficits in electrosensory function. We examined a
      neural correlate of such jamming at the level of the midbrain. Previous results
      indicate that neurons in the dorsal layers of the torus semicircularis can (1)
      respond to jamming signals, (2) respond to moving electrosensory stimuli, and (3)
      receive convergent information from the four sensory maps of the electrosensory
      lateral line lobe (ELL). In this study we recorded the intracellular responses of
      both tuberous and ampullary neurons to moving objects. Robust Gaussian-shaped or
      sinusoidal responses with half-height durations between 55 ms and 581 ms were
      seen in both modalities. The addition of ongoing global signals with temporal
      frequencies of 5 Hz attenuated the responses to the moving object by 5 dB or
      more. In contrast, the responses to the moving object were not attenuated by the
      addition of signals with temporal frequencies of 20 Hz or greater. This occurred
      in both the ampullary and tuberous systems, despite the fact that the ampullary
      afferents to the torus originate in a single ELL map whereas the tuberous
      afferents emerge from three maps.

PMID- 16001181
TI  - Efficacy of risedronate in men with primary and secondary osteoporosis: results
      of a 1-year study.
AB  - Osteoporosis is prevalent in men with an estimated one in eight men older than 50
      years suffering from osteoporotic fracture, and a higher mortality rate after
      fracture among men compared with women. There are few approved therapies for
      osteoporosis in men. This observational study assesses the efficacy and safety of
      risedronate in the treatment of men with primary and secondary osteoporosis. A
      single-center, open label, randomized, prospective 1-year study was conducted in
      men with primary or secondary osteoporosis. Patients were randomized to
      risedronate (risedronate 5 mg/day plus calcium 1,000 mg/day and vitamin D 800
      IU/day) or control groups (alfacalcidol 1 mug/day plus calcium 500 mg/day or
      vitamin D 1,000 IU/day plus calcium 800 mg/day). Bone mineral density (BMD)
      measurements, X-rays of the spine, a medical history and physical exam, and
      patient self-assessments of back pain were performed at baseline and 12 months.
      Blinded semi-quantitative fracture assessment was conducted by a radiologist. A
      total of 316 men with osteoporosis were enrolled in the trial (risedronate,
      n=158; control, n=158). At 1 year lumbar spine BMD increased by 4.7% in the
      risedronate group versus an increase of 1.0% in the control group (P<0.001).
      Significant increases in BMD at the total hip and femoral neck were also observed
      with risedronate compared with the control group. The incidence of new vertebral
      fracture in the risedronate group was reduced by 60% versus the control group
      (P=0.028). Daily treatment with risedronate for 12 months significantly increased
      BMD at the lumbar spine, femoral neck and total hip and significantly reduced the
      incidence of new vertebral fractures. This is the first prospective, randomized,
      controlled trial to demonstrate a significant reduction in vertebral fractures in
      1 year in men with primary or secondary osteoporosis.

PMID- 16001183
TI  - Development of swimming in the medicinal leech, the gradual acquisition of a
      behavior.
AB  - Observing the development of behavior provides an assay for the developmental
      state of an embryo's nervous system. We have previously described the development
      of behaviors that were largely confined to one or a few segments. We now extend
      the work to a kinematic analysis of the development of swimming, a behavior that
      requires coordination of the entire body. When leech embryos first begin to swim
      they make little forward progress, but within several days they swim as
      effectively as adults. This increase in efficacy depends on changes in body shape
      and on improved intersegmental coordination of the swim central pattern
      generator. These kinematic details suggest how the swim central pattern
      generating circuit is assembled during embryogenesis.

PMID- 16001184
TI  - Temporal resolution of the Florida manatee (Trichechus manatus latirostris)
      auditory system.
AB  - Auditory evoked potential (AEP) measurements of two Florida manatees (Trichechus
      manatus latirostris) were measured in response to amplitude modulated tones. The
      AEP measurements showed weak responses to test stimuli from 4 kHz to 40 kHz. The
      manatee modulation rate transfer function (MRTF) is maximally sensitive to 150
      and 600 Hz amplitude modulation (AM) rates. The 600 Hz AM rate is midway between
      the AM sensitivities of terrestrial mammals (chinchillas, gerbils, and humans)
      (80-150 Hz) and dolphins (1,000-1,200 Hz). Audiograms estimated from the input
      output functions of the EPs greatly underestimate behavioral hearing thresholds
      measured in two other manatees. This underestimation is probably due to the
      electrodes being located several centimeters from the brain.

PMID- 16001185
TI  - Analysis of spectral shape in the barn owl auditory system.
AB  - In a behavioral experiment, we investigated how efficiently barn owls (Tyto alba)
      could detect changes in the spectral profile of multi-component auditory signals
      with stochastic envelope patterns. Signals consisted of one or five bands of
      noise (bandwidth 4, 16, or 64 Hz each; center frequencies 1.02, 1.43, 2.0, 2.8,
      3.92 kHz). We determined increment thresholds for the 2 kHz component for three
      conditions: single-band condition (only the 2 kHz component), all five noise
      bands with the envelope fluctuations of the bands being either correlated or
      uncorrelated. Noise bandwidth had no significant effect on increment detection.
      Increment thresholds for the different conditions, however, differed
      significantly. Thresholds in correlated conditions were generally the lowest of
      all conditions, whereas, thresholds in uncorrelated conditions mostly resulted in
      the highest thresholds. This can be interpreted as evidence for comodulation
      masking release in barn owls. If the increment in the 2 kHz component is balanced
      by decrementing the four flanking bands in amplitude, increment detection
      thresholds are not affected. The data suggest that the barn owls used information
      from simultaneous spectral comparison across different frequency channels to
      detect spectral changes in multi-component noise signals rather than sequential
      comparison of overall stimulus levels.

PMID- 16001186
TI  - Factors influencing the radiative surface temperature of grey seal (Halichoerus
      grypus) pups during early and late lactation.
AB  - The aim of this study was to examine the variation in body surface temperature of
      grey seal (Halichoerus grypus) pups throughout lactation in response to different
      environmental conditions. Radiative surface temperatures (T (r), degrees C) of
      pups were measured on the Isle of May (56 degrees 11'N, 02 degrees 33'W),
      southeast Scotland from 29 October to 25 November 2003. Records were obtained
      from a total of 60 pups (32 female and 28 male) from three different pupping
      sites during early and late lactation. Pups were sheltered from high wind speeds
      but air temperature, humidity and solar radiation at pupping sites were similar
      to general meteorological conditions. The mean T (r) of all pups was 15.8 degrees
      C (range 7.7-29.7 degrees C) at an average air temperature of 10.2 degrees C
      (range 6.5-13.8 degrees C). There was no difference in the mean T (r) of pups
      between early and late lactation. However, the T (r) varied between different
      regions of the body with hind flippers on average 2-6 degrees C warmer than all
      other areas measured. There was no difference in mean T (r) of male and female
      pups and pup body mass did not account for the variation in T (r) during early or
      late lactation. Throughout the day there was an increase in the T (r) of pups and
      this explained 20-28% of the variation in T (r) depending on stage of lactation.
      There was no difference in the mean T (r) of pups between pupping sites or
      associated with different substrate types. Wind speed and substrate temperature
      had no effect on the T (r) of pups. However, solar radiation, air temperature and
      relative humidity accounted for 48% of the variation in mean T (r) of pups during
      early lactation. During late lactation air temperature and solar radiation alone
      accounted for 43% of the variation in T (r). These results indicate that
      environmental conditions explain only some of the variation in T (r) of grey seal
      pups in natural conditions. Differences in T (r) however indicate that the cost
      of thermoregulation for pups will vary throughout lactation. Further studies
      examining intrinsic factors such as blubber thickness and activity levels are
      necessary before developing reliable biophysical models for grey seals.

PMID- 16001187
TI  - High ambient ammonia promotes growth in a ureogenic goby, Mugilogobius abei.
AB  - Mugilogobius abei has the ability to produce large amounts of urea when exposed
      to high ambient ammonia. Despite this metabolically costly approach, and reports
      of growth inhibition effects of ammonia on fish, M. abei exposed to ammonia shows
      no adverse effects on growth. To investigate this observation the growth of M.
      abei was measured at room temperatures for 8 weeks at a constant ration level
      under solitary and grouped conditions, in 20% SW with or without (control) 2 mM
      NH(4)Cl. Furthermore, pituitary mRNA levels of growth hormone, oxygen
      consumption, incorporation of external (15)N-ammonia into amino acid and protein
      fractions as well as behavioral activities were also examined. The specific
      growth rates of ammonia-exposed fish under grouped condition over the 8 weeks
      were significantly higher than those of control, while those rates under solitary
      condition were not significantly different between the treatments. The pituitary
      of ammonia-exposed fish had higher growth hormone mRNA than in control fish. The
      use of (15)N isotope revealed that M. abei can actively use external ammonia as a
      supplementary nitrogen source. Oxygen consumption of ammonia-exposed fish was
      significantly lower than that of control fish. Locomotor activity and aggressive
      behavior under grouped condition were significantly reduced in ammonia-exposed
      fish as compared to those of control. These combined alterations in the ammonia
      exposed fish may result in the higher growth rates.

PMID- 16001188
TI  - Evaluation of the relationship between endometrial thickness and failure of
      single-dose methotrexate in ectopic pregnancy.
AB  - OBJECTIVE: To test the hypothesis that endometrial stripe thicker than 12 mm
      increases treatment failure of single-dose methotrexate for the management of
      ectopic pregnancy. STUDY DESIGN: Seventy-three patients with ectopic pregnancy
      and measured pretreatment endometrial stripe were divided into two groups based
      on the endometrial stripe thickness (> 12 mm or < or = 12 mm). All patients were
      candidates for single-dose methotrexate treatment. Variables analyzed between the
      two groups were endometrial stripe thickness, initial beta human chorionic
      gonadotropin level (hCG), size of the ectopic mass, presence of fetal heart
      tones, previous ectopic pregnancy, and clinical outcomes. RESULTS: Sixty patients
      had endometrial stripe thickness < or = 12 mm and 13 patients > 12 mm. The two
      groups were similar in initial hCG, size of ectopic mass, presence of fetal heart
      tones and rate of previous ectopic pregnancy. The failure rate was significantly
      higher in the group with endometrial stripe > 12 mm compared to the group < or =
      12 mm (n=7, 53% vs. n=3, 5%, P<0.01). The endometrial stripe was significantly
      thicker in the group with endometrial stripe thickness > 12 mm compared to the
      group < or = 12 mm (mean +/- SD, 17.64+/-5.82 mm vs. 7.69+/-2.82 mm, P<0.01).
      CONCLUSION: Endometrial stripe thicker than 12 mm increases the risk for
      treatment failure with single-dose methotrexate.

PMID- 16001189
TI  - Post-menopausal vaginal angiomyofibroblastoma: a case report.
AB  - Angiomyofibroblastoma (AMF) is a recently described, rare, benign soft tissue
      vulvovaginal tumour that occurs mainly but not exclusively in the vulval region
      of pre-menopausal women (Fletcher et al. in Am J Surg Pathl 16:373; 1992). The
      first case was diagnosed in 1992. We report a case of a post-menopausal woman
      with a 2-month history of a rapidly growing painless vaginal tumour and thus
      drawing the attention of gynaecologist as well as general practitioners to the
      fact that this rare phenomenon can occur outside the vulva.

PMID- 16001190
TI  - Adenomyosis interferes with accurate ultrasonographic detection of uterine
      leiomyomas.
AB  - OBJECTIVE: To evaluate the accuracy of pelvic ultrasonography, and the
      characteristics of women with inaccurate ultrasonographic diagnosis for uterine
      leiomyomas. MATERIALS AND METHODS: Preoperative pelvic ultrasonographic and
      postoperative pathologic findings of all women, who underwent hysterectomies for
      pelvic pain, menorrhagia and/or leiomyomas between December 1995 and July 2002,
      were evaluated. Three hundred thirty-three women, who had a transabdominal or
      transvaginal pelvic ultrasonography within 1 year prior to the hysterectomy, were
      included in the study. We assessed the accuracy of ultrasonography for uterine
      leiomyomas in this group, and defined the characteristics of women with
      inaccurate studies. RESULTS: Despite its high sensitivity (95.9%),
      ultrasonography had only 42.5% specificity for detecting leiomyomas. Its positive
      predictive and the negative predictive values were 92.4% and 58.6%, respectively.
      Adenomyosis was found in the majority of the women with false-positive (70.8%)
      and false-negative (83.3%) results. In both groups, previous pelvic surgery and
      high body mass index (BMI) were also common. CONCLUSION: Adenomyosis is the most
      common final diagnosis in women with inaccurate ultrasound reports for uterine
      leiomyomas.

PMID- 16001191
TI  - Pre-eclampsia: is it a different disease in primiparous and multiparous women?
AB  - The aim of this study was to evaluate differences in clinical and laboratory
      parameters and differences in the complication rates between pre-eclamptic
      primiparous and pre-eclamptic multiparous women. A prospective case series of 112
      primiparous and 186 multiparous women with pre-eclampsia was conducted at
      Princess Badea Teaching Hospital; a large tertiary public health service hospital
      in Irbid, North Jordan. A uniform medical and surgical management protocol was
      implemented. The main outcome measures included antenatal, intrapartum and
      puerperal, maternal and foetal complications. Multiple maternal and foetal
      demographic, clinical and laboratory parameters were studied. As expected, the
      primiparous were younger than the multiparous women. After adjusting for maternal
      age, regression analysis revealed no difference in the systolic or diastolic
      blood pressure in the two groups. It was also demonstrated that there was no
      statistically significant difference in the clinical presentation, haematological
      and biochemical parameters or ultimate maternal outcome between the two groups.
      After adjusting for babies' sex and gestational age, it was demonstrated that
      there was no statistically significant difference in the following: gestational
      age at delivery, foetal weight, stillbirth, admission rate to neonatal intensive
      care unit, neonatal death rate within the first four weeks after birth and
      incidence of intrauterine growth restriction between the two groups.

PMID- 16001192
TI  - Effect of vaginal metronidazole + miconazole treatment during pregnancy for
      gestational age and birth weight in a population-based study.
AB  - The objective of the study was to check the effect of the combination of
      metronidazole and miconazole (M+M) for the prevention of sexually transmitted
      infections/disorders related preterm delivery/birth. Antiprotozoal vaginal
      metronidazole was not able to prevent preterm birth, while the antifungal topical
      miconazole use showed some reduction in preterm birth in our previous studies.
      The population-based large control (without any defects) data set of the
      Hungarian Case-Control Surveillance System of Congenital Abnormalities was used
      for the evaluation of the combination of M+M for birth outcomes. Of 38,151
      controls, 846 (2.2%) had treatment with vaginal tablet of M+M for vaginal
      infections. The prevalence of preterm birth was 9.5% after this treatment
      compared with the 9.2% of preterm birth in the untreated group. Thus the
      combination of M+M was not able to reduce the preterm birth associated with
      vulvovaginal infections/disorders.

PMID- 16001193
TI  - Programmed cell death (apoptosis) in placentas from normal pregnancy and
      pregnancy complicated by term (t) and preterm (p) premature rupture of membranes
      (PROM).
AB  - OBJECTIVE: The aim of this study was to determine the apoptotic index using three
      different apoptotic markers: terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end labeling (TUNEL); M30 cytoDEATH antibody and
      fluorescein isothiocyanate (FTIC)-labeled annexin-V in the placenta and membranes
      from normal pregnancy and pregnancy complicated by premature rupture of membranes
      (PROM). STUDY DESIGN: Placentas from 16 pregnancies (22-40 weeks' gestation) and
      13 pregnancies complicated by pPROM and tPROM were collected at delivery.
      Maternal and gestational age, mode of delivery, gravidity and parity, fetal
      birthweight, Apgar scores, presence of histologic chorioamnionitis, interval
      between membrane rupture and delivery were recorded among PPROM and tPROM cases.
      RESULTS: Only M30 cytoDEATH antibody (P=0.02) and TUNEL test (P=0.04) on fetal
      membranes gave statistically significantly higher levels in cases with premature
      rupture of membranes. The presence of histologic chorioamnionitis had no
      significant impact on apoptotic markers in PROM placentas. Preterm deliveries
      following the rupture of membranes had higher median AI values detected by M30M
      antibody, compared to those cases delivered without PROM (P=0.03). CONCLUSION:
      High apoptotic nuclei counts were found in fetal membranes of pPROM.

PMID- 16001194
TI  - Fertility sparing therapy for ovarian cancer has inherent risks and benefits.
AB  - INTRODUCTION: Fertility sparing therapy for epithelial ovarian cancer has been
      suggested for well-selected patients with early stage disease. The overall
      recurrence rate of 10% and 5-year disease free survival greater than 90% is
      similar in conservative and traditional surgical management of epithelial ovarian
      cancer. Thus, conservative approaches may be considered in young women diagnosed
      with FIGO stage I cancer who wish to preserve reproductive function. Subsequent
      use of assisted reproductive technologies (ART) may facilitate production of
      biologic offspring in these cancer survivors. However, each candidate requires
      unique consideration by subspecialists to avoid potentially fatal management
      errors. CASE REPORT: We present two cases in which fertility sparing therapy for
      early stage epithelial ovarian cancer was considered. The first case delineates
      the comprehensive work-up required to identify candidates for this therapy, while
      the second case illustrates the successful application of a fertility sparing
      approach. DISCUSSION: The conservative management of early epithelial ovarian
      cancer and use of ART to obtain offspring are reviewed.

PMID- 16001195
TI  - Weekly carboplatin in a frail elderly woman with advanced peritoneal carcinoma.
AB  - INTRODUCTION: Standard chemotherapy for ovarian, peritoneal and fallopian tube
      carcinoma has been a combination of carboplatin (AUC = 6) and paclitaxel 175
      mg/m2 every 3 weeks. For frail and elderly patients who may not tolerate the
      toxicity associated with combination chemotherapy there is the option of omitting
      paclitaxel and giving carboplatin (AUC = 6) as a single agent every 3 weeks. The
      toxicity may be reduced further, without decreasing effectiveness, by giving
      single-agent carboplatin at a reduced dose (AUC = 2) every week. CASE REPORT: A
      frail 79-year-old woman with advanced peritoneal carcinoma had first-line and
      second-line chemotherapy with single-agent carboplatin on day 1 every 7 days.
      This has resulted in disease stabilization, CA-125 partial response and improved
      quality of life. Toxicity has been negligible. CONCLUSION: Weekly carboplatin is
      an attractive option for the treatment of frail and elderly patients with
      ovarian, peritoneal and fallopian tube carcinoma.

PMID- 16001196
TI  - Vaginal intraepithelial neoplasia: clinical-therapeutic analysis of 33 cases.
AB  - Vaginal intraepithelial neoplasia (VAIN) represents 1% of all intraepithelial
      neoplasia of the lower genital tract. Our aim was to study the clinical
      therapeutic characteristics of patients with VAIN. A retrospective study was made
      of all cases of patients, who attended within the outpatient service between 1993
      and 2003, with a diagnosis of VAIN. During this period, 84,293 Papanicolaou
      smears (triple collection) were performed and a total of 33 (50.32+/-11.5 years
      old) patients with VAIN were diagnosed. Among these patients, twenty-six (78.8%)
      were white, 17 (51.5%) were smokers, and 23 (69.6%) had undergone hysterectomy
      previously. The indications for hysterectomy prior to the appearance of VAIN were
      found in 20 cases (87%) of cervical intraepithelial or invasive neoplasia (CIN),
      and in two (8.6%) cases after myoma uterine. The median time elapsed between the
      hysterectomy and the appearance of VAIN was 41 months. Thirteen (39.4%), 11
      (33.3%) cases were, respectively, VAIN II and III. Twenty-eight patients (84.8%)
      presented a single lesion affecting the upper third of the vagina. The commonest
      finding was the presence of white epithelium in 17 patients (51.5%). Ten of 16
      cases submitted to topical application of 5-fluorouracil (5-FU) achieved
      remission. Surgery was utilized for seven patients, of whom six achieved
      remission and one had persistence of the lesion. We conclude that VAIN may occur
      in patients who have undergone hysterectomy due to benign alterations. This
      justifies the use of routine Papanicolaou tests. Both surgical and 5-FU
      treatments are efficient.

PMID- 16001197
TI  - The detection of CMV in amniotic fluid and cervicovaginal smear samples by real
      time PCR assay in prenatal diagnosis.
AB  - OBJECTIVE: There is no specific antiviral therapy or a vaccine, which could be
      safely administered to the pregnant women with primary human cytomegalovirus
      (CMV) infection. Therefore, prenatal diagnosis has a critical role in the
      management of pregnancy, complicated by this disease. In this study, we
      investigated the prevalence and clinical consequences of human CMV infection from
      cervicovaginal smear and amniotic fluid samples of pregnant women by using real
      time polymerase chain reaction (RT-PCR) assay, in one of the Obstetrics and
      Gynecology outpatient clinics of Turkey. The identification of reliable
      prognostic markers of fetal disease remains the main purpose and a major
      challenge on this issue. METHODS: Two hundred and six samples, of which 135 were
      cervicovaginal smear and 71 were amniotic fluid, were enrolled in the study. The
      DNAs of the samples were extracted by using Roche Diagnostic (Roche, Germany) kit
      and amplifications of these DNAs were studied by using Light-Cycler system (Roche
      Germany) as being quantitative. Anti-CMV IgM antibodies in the samples were
      studied by both MEIA (Imx system, Abbot Laboratories, USA) and a commercial ELISA
      kit (Radim SPA, Italy) while anti-CMV IgG antibodies were studied by MEIA (Axsym
      system, Abbot Laboratories, USA). RESULTS: Human CMV DNA was found to be positive
      in 1.5% (2 in 135) of cervicovaginal smear and 1.4% (1 in 71) of amniotic fluid
      samples by RT-PCR. IgM and IgG were found to be negative in all of the
      cervicovaginal smear samples by both MEIA and ELISA, while IgG antibody was found
      to be positive in only one of the amniotic fluid samples by MEIA. CONCLUSION:
      With RT-PCR assay, we have found the prevalence of human CMV in pregnant women
      similar to epidemiologic reports, which have been described earlier. Whereas the
      fetus with positive amniotic fluid in favor of human CMV had an intrauterine
      growth restriction resulted in intrauterine exitus, no symptoms were observed in
      the infants of the other two pregnant women with positive RT-PCR results. The
      fact that the clinical consequence of the newborn whose amniotic fluid evaluation
      revealed human CMV infection by RT-PCR made us think that this molecular
      diagnosis method may be a reliable assay in prenatal diagnosis of this pathogen.

PMID- 16001198
TI  - The value of sonohysterography in detecting intracavitary benign abnormalities.
AB  - The aim of this retrospective study was to assess the diagnostic value and the
      usefulness of sonohysterography in the detection of uterine intracavitary benign
      abnormalities, compared with other diagnostic methods (transvaginal
      ultrasonography and diagnostic hysteroscopy). From January 2003 to December 2003,
      a total of 73 patients (47 premenopausal (middle age 38.9) and 26 postmenopausal
      women (middle age 60.5)) underwent transvaginal ultrasonography (TVS) and
      sonohysterography (SHG), consisting of an intrauterine infusion of saline
      solution during transvaginal ultrasound. The women referred to our
      Ultrasonography Center because of intermenstrual (38) or postmenopausal bleeding
      (19), or an abnormal or a poorly defined endometrial interface (16) as seen as
      baseline ultrasonography. The findings at TVS and SHG were compared with
      hysteroscopy (HS). In one case, the SHG was technically impossible to perform. In
      premenopausal group the sensitivity of SHG had been 100% in detecting submucosal
      fibroids, endometrial polyps and hyperplasia and 75% in detecting normal uterus.
      The specificity had been always 100%. In postmenopausal group the sensitivity of
      SHG had been 75% in detecting submucosal fibroids, 93.8% in endometrial polyps
      and 100% in hyperplasia and normal uterus. The specificity had been 100% in
      submucosal fibroids and hyperplasia and had been 90.0 and 95.5% in endometrial
      polyps and normal uterus, respectively. SHG allows to obtain a precise diagnosis
      of benign uterine pathology and it is more accurate in the diagnosis of
      intracavitary abnormalities than that obtained by TVS. Preoperative use of SHG
      may assist in choosing the best surgical treatment for the patient.

PMID- 16001199
TI  - Related factors in bone mineral density of lumbal and femur in natural
      postmenopausal women.
AB  - OBJECTIVE: To assess possible factors affecting the bone mineral density (BMD) in
      postmenopausal women. METHODS: A retrospective analysis of 267 cases with
      spontaneous menopause within 3 years of period was performed. None of the
      enrolled cases were taken any hormone replacement therapy and/or treatment for
      osteoporosis. BMD measurements were done in lumbal vertebral (L1-L4) and left
      femur (neck, intertrochanteric and ward triangle) via dual energy X-ray
      absorbtiometry (DEXA) method, yielding corresponding T-scores of above-mentioned
      areas. In addition, age at menarche, parity, menopausal age, duration of
      postmenopausal state, lactation, physical activity, cigarette smoking, dietary
      calcium intake, oral contraceptive use and body mass index (BMI) were determined.
      RESULTS: There were no relationships between BMD and age at menarche, parity,
      menopausal age, lactation, physical activity, smoking, dietary calcium intake and
      oral contraceptive use. Two associated factors with BMD were BMI and time since
      menopause. BMI was found to be positively and time since menopause was negatively
      correlated with BMD of both lumbal region and femur. CONCLUSIONS: BMD changes and
      its related factors should be kept in mind during postmenopausal years.
      Therefore, adequate peak bone mass and related life style measures should be
      achieved to confront osteoporosis-related symptoms and its consequences.

PMID- 16001200
TI  - Comparison of isosorbide mononitrate (Mono Mack) and misoprostol (Cytotec) for
      cervical ripening in the first trimester missed abortion.
AB  - OBJECTIVE: The objective of this study was to compare NO-donor isosorbide
      mononitrate to misoprostol, both applied as vaginal tablets for cervical ripening
      prior to first trimester curettage in patients with missed abortion. MATERIALS
      AND METHODS: Thirty women with missed abortion were assigned after a random list
      to be treated either with 200 microg gemeprost (Cytotec, Pfizer, Germany) or with
      40 mg isosorbide mononitrate for cervical priming at least 3 h before curettage.
      Vaginal bleeding or the intracervical presence of products of conception was
      documented. The largest number of Hegar's dilator, which could be introduced
      without difficulty and the largest number of Hegar's dilator at which cervical
      dilation was performed and the ease of mechanical dilation was assessed. RESULTS:
      There were no significant differences in cervical ripeness before procedure nor
      in ease of dilation. In the misoprostol group, the cervical canal was more
      dilated before any procedure (median of Hegar's dilator 6 vs. 5) and after
      dilation (median of Hegar's dilator 11 vs. 10), although this difference was not
      significant. Vaginal bleeding occurred in two patients in each group. Products of
      conception were only found in the cervix of one patient of the misoprostol group.
      SYNOPSIS: Vaginal application of isosorbidemononitrate in cervical priming prior
      to curettage abortion is as effective as vaginal application of misoprostol.

PMID- 16001201
TI  - EMG-biofeedback assisted pelvic floor muscle training is an effective therapy of
      stress urinary or mixed incontinence: a 7-year experience with 390 patients.
AB  - PURPOSE: The aim of the study was to determine the short- and long-term efficacy
      of an intensive and EMG-biofeedback-assisted pelvic floor muscle training (PFMT)
      program as a therapy of female stress or mixed urinary incontinence. MATERIALS
      AND METHODS: All women with stress or mixed urinary incontinence treated in the
      pelvic floor reeducation program at our clinic between September 1996 and March
      2003 were included. EMG-biofeedback assisted PFMT was performed by specially
      trained therapists (one registered nurse and one midwife). Electric stimulation
      preceded PFMT if the pelvic floor muscle contractions were considered too weak
      for active training (Oxford < 2). Examinations included among others:
      conventional urodynamic studies prior to therapy, a stress provocation test
      (cough test), and determination of maximal pelvic floor muscle strength (Oxford
      grading and electric EMG-potential). A retrospective chart review was performed.
      A questionnaire was administered for long-term follow-up. RESULTS: Four hundred
      and thirty four women attended our PFR-program in this 7-year period. All 390
      women with stress (80%) or mixed (20%) urinary incontinence were evaluated. Mean
      age: 52 years. Mean duration of incontinence: 6.7 years. Two hundred and sixty
      three women completed the training (group 1, average number of training sessions:
      8.7), 127 patients ended therapy prematurely (group 2, average number of training
      sessions: 4.1). Short-term results at the end of the PFR-program are available
      for group 1. There was a statistically significant improvement of the stress
      provocation test (cough test). The data before the therapy was 141x SUI degrees
      III (60%); 50x SUI degrees II (21%), 24x SUI degrees I (10%), 20x SUI degrees 0
      (9%) as opposed to after the therapy 9x SUI degrees III (5%), 34x SUI degrees II
      (19%), 48x SUI degrees I (26%), 91x SUI degrees 0 (50%). There was a significant
      increase in the Oxford-score by 1.2 points (2.9-4.1; P<0.001). Self-reported
      improvement of incontinence symptoms was 95%. The electric EMG-potentials almost
      doubled (11.3-20.5 muV; P<0.001). Long-term results (questionnaire) for all
      patients: the average follow-up time was 2.8 years (range: 3 months to 7 years).
      Three hundred and twelve (80%) of the questionnaires returned. Seventy-one
      percent of them self-reported a persisting improvement of their incontinence
      symptoms. Thirteen percent of all women underwent incontinence surgery following
      the completion of conservative therapy (9.2% group 1, 25% group 1; P<0.001).
      CONCLUSIONS: An intensive and EMG-biofeedback assisted PFMT is very effective.
      Often, avoidance of surgery is possible.

PMID- 16001202
TI  - Fetal weight, maternal age and height are poor predictors of the need for
      caesarean section for arrest of labor.
AB  - Retrospective data on 228 patients was analyzed in order to develop a predictive
      model of operative delivery, caesarean section for arrest of labor. The ANOVA,
      discriminant analysis and the Fisher discriminant function of SPSS were used.
      Birth weight, maternal age and maternal height were statistically significant
      risk factors, but only 10.9% of caesarean sections could be predicted with these
      variables. Seven percent of patients who delivered vaginally were predicted as
      needing a caesarean section for arrest of labor.

PMID- 16001203
TI  - Differentiation of activated satellite cells in denervated muscle following
      single fusions in situ and in cell culture.
AB  - Satellite cells represent a cellular source of regeneration in adult skeletal
      muscle. It remains unclear why a large pool of stem myoblasts in denervated
      muscle does not compensate for the loss of muscle mass during post-denervation
      atrophy. In this study, we present evidence that satellite cells in long-term
      denervated rat muscle are able to activate synthesis of contractile proteins
      after single fusions in situ. This process of early differentiation leads to
      formation of abnormally diminutive myotubes. The localization of such dwarf
      myotubes beneath the intact basal lamina on the surface of differentiated muscle
      fibers shows that they form by fusion of neighboring satellites or by the progeny
      of a single satellite cell following one or two mitotic divisions. We
      demonstrated single fusions of myoblasts using electron microscopy,
      immunocytochemical labeling and high resolution confocal digital imaging.
      Sequestration of nascent myotubes by the rapidly forming basal laminae creates a
      barrier that limits further fusions. The recruitment of satellite cells in the
      formation of new muscle fibers results in a progressive decrease in their local
      densities, spatial separation and ultimate exhaustion of the myogenic cell pool.
      To determine whether the accumulation of aberrant dwarf myotubes is explained by
      the intrinsic decline of myogenic properties of satellite cells, or depends on
      their spatial separation and the environment in the tissue, we studied the fusion
      of myoblasts isolated from normal and denervated muscle in cell culture. The
      experiments with a culture system demonstrated that the capacity of myoblasts to
      synthesize contractile proteins without serial fusions depended on cell density
      and the availability of partners for fusion. Satellite cells isolated from
      denervated muscle and plated at fusion-permissive densities progressed through
      the myogenic program and actively formed myotubes, which shows that their
      myogenic potential is not considerably impaired. The results of this study
      suggest that under conditions of denervation, progressive spatial separation and
      confinement of many satellite cells within the endomysial tubes of atrophic
      muscle fibers and progressive interstitial fibrosis are the important factors
      that prevent their normal differentiation. Our findings also provide an
      explanation of why denervated muscle partially and temporarily is able to restore
      its functional capacity following injury and regeneration: the release of
      satellite cells from their sublaminal location provides the necessary space for a
      more active regenerative process.

PMID- 16001204
TI  - Prevalence and risk factors for self-reported odour intolerance: the Skovde
      population-based study.
AB  - OBJECTIVES: The present study was performed to determine the prevalence of odour
      intolerance in adults with respect to both self-reported general intolerance and
      affective and behavioural consequences. Furthermore, we aimed to relate odour
      intolerance to explanatory variables and risk factors. METHOD: This is a cross
      sectional, population-based epidemiological study. A random sample of 1900
      inhabitants from the age of 20, stratified for age and gender, were recruited.
      Subjects were invited for clinical examinations that included questions about
      general odour intolerance, respiratory symptoms and smoking habits, as well as a
      smell identification test. The chemical sensitivity scale for sensory
      hyperreactivity (CSS-SHR) was used to quantify affective and behavioural
      consequences. RESULTS: In total 1387 volunteers (73% of the sample) were
      investigated. The overall prevalence of self-reported general odour intolerance
      was 33% (95% confidence interval (CI): 30-36%), with problems mainly from the
      upper respiratory tract. The prevalence of affective and behavioural consequences
      of odour intolerance (CSS-SHR score > or =43) was 19% (95% CI: 15-22%). The risk
      for the latter condition was increased in women compared with men (odds ratio =
      2.3: 95% CI: 1.5-3.6), but no increased risk was found related to current smoking
      or impaired sense of smell. CONCLUSION: This study demonstrates that intolerance
      to odours is a widespread problem in society, and that it is about twice as
      common in women than in men.

PMID- 16001205
TI  - Nephrolithiasis in a worker with cadmium exposure in the past.
AB  - OBJECTIVES: A clinical case regarding a cadmium-exposed worker is described.
      CLINICAL CASE: The subject during the work as welder (male, 42-years-old at the
      time of the first investigation) developed a Fanconi-like syndrome due to high
      exposure to cadmium fumes. Ten years after exposure removal, the subject showed
      clinical and laboratory evidence of nephrolithiasis (calcium phosphate stones).
      CONCLUSIONS: The clinical case confirms the possibility of nephrolithiasis in
      cadmium-exposed workers and suggests that susceptible subjects may develop kidney
      stones after lesion of the tubular cells.

PMID- 16001206
TI  - Dermal absorption and urinary elimination of N-methyl-2-pyrrolidone.
AB  - OBJECTIVES: The dermal absorption of the solvent N-methyl-2-pyrrolidone (NMP) and
      its elimination in urine was investigated in an experimental study. METHODS:
      Seven volunteers were exposed to 1045 mg of liquid NMP under occlusive conditions
      for 2 h. Urine was collected before, during and up to 72 h after the exposure and
      analysed for NMP by GC/MS after liquid-liquid extraction. Additionally, the
      remaining NMP in the pads was determined to estimate the total dermal uptake.
      RESULTS: The concentration of NMP in urine increased rapidly after beginning of
      the exposure up to 1 h after the exposure was completed. A peak concentration of
      1,836+/-863 microg/l was observed, the half-life in urine was 3.2 h. About 0.5%
      of the absorbed dose was excreted metabolically unchanged. An average dermal
      absorption of 5.5 mg cm(-2) h(-1) was calculated. CONCLUSIONS: The results of
      this study show that the percutaneous absorption of NMP may contribute
      significantly to the overall uptake of the solvent, e.g. in the workplace.
      Therefore, a biological monitoring of NMP exposed workers is essential for
      occupational-medical surveillance.

PMID- 16001207
TI  - Dermal and bronchial symptoms in children: are they caused by PAH containing
      parquet glue or by passive smoking?
AB  - OBJECTIVE: In 1997 a new source of potential polycyclic aromatic hydrocarbon
      (PAH) exposure was discovered: very high levels of (PAHs) and benzo-a-pyrene
      (BaP) were detected in household dust from former American Forces housing in
      Frankfurt am Main, Germany, built in 1955/1956. This contamination was caused by
      a parquet glue containing coal tar, the use of which was formerly a standard
      building practice in Germany. Children were considered to be at special risk for
      exposure to PAHs when playing on the floor via mouthing. Therefore, the
      children's symptoms and complaints were analysed for association with PAH
      contamination in parquet glue and household dust as well as with internal
      exposure to PAHs via determination of 1-hydroxypyrene in urine samples.
      PARTICIPANTS AND METHODS: Two hundred and eighty seven children <6 years of age
      living more than 12 months in the former US-housing estates are enrolled in this
      analysis, representing 22.3% of the children <6 years of age living there. Their
      spot urine samples were analysed for 1-hydroxypyrene. The level of BaP in parquet
      glue and in household dust was available in the homes of 215 and 212 children,
      respectively. There were no hints for differences in PAH contamination in parquet
      glue or in household dust of the participants' flats compared to the flats of the
      non responders. In 246 cases data on environmental tobacco smoke exposure at home
      was known as well. Data on symptoms and complaints observed by their parents
      during the preceding 12 months (1-year prevalence) were obtained using the ISAAC
      questionnaire (modified). RESULTS: The following 1-year prevalences were
      reported: 15% itching eczema in elbows, 10% itching and urticaria, 6% itching in
      the palate and throat, 20% sneezing and running nose or stuffed nose, 15%
      nosebleed; 25% wheezing, 42% dry cough, and 60% frequent infectious disease. No
      consistent associations between symptoms and BaP in parquet glue or in household
      dust or urinary levels of 1-hydroxypyrene in the children could be found.
      However, associations between symptoms and exposure to environmental tobacco
      smoke at home were to be seen, significant for dermal and bronchial symptoms.
      CONCLUSION: Informed about PAHs in parquet glue and household dust many parents
      demanded for total redevelopment of their flats. According to statistical
      evaluation of the children's symptoms, observed by their parents, no hints for an
      association with exposure via BaP in parquet glue or household dust were found.
      However, significant associations between symptoms and the exposure to
      environmental tobacco smoke were observed, especially bronchial and dermal
      symptoms. Therefore instead of redevelopment of flats with parquet glue
      containing coal tar, intensified information on the harmful effects of passive
      smoking in childhood seems to be mandatory.

PMID- 16001208
TI  - Predictors of changes in sick leave in workers with asthma: a follow-up study.
AB  - OBJECTIVE: The aim of this prospective study was to investigate predictors of 1
      year changes in sick leave in workers with asthma. METHODS: The initial cohort
      consisted of 111 workers with asthma. One-hundred and one participants completed
      the follow-up after 1 year. Self-reported sick leave over the past 12 months was
      reported at baseline and at follow-up. At the start of this study, all
      participants completed questionnaires on adaptation to functional limitations,
      psychosocial variables, working conditions, lung function characteristics,
      disease history characteristics, health complaints and functional limitations,
      and person characteristics ('potential predictors'). Three multivariate logistic
      regression models were calculated, with an increase in sick leave, a decrease in
      sick leave, and stable high sick leave as dependent (outcome) variables, and the
      potential predictors as independent (explanatory) variables. RESULTS: An increase
      in sick leave was predicted by a lower level of education and perceiving more
      functional limitations in activities of daily life. A decrease in sick leave was
      predicted by spending all energy at work less often and perceiving fewer health
      complaints in social activities (adaptation criteria 4 and 5). Stable high sick
      leave was predicted by less job satisfaction, perceiving more support from the
      employer and perceiving more health complaints in social activities (adaptation
      criterion 5). Lung function characteristics, or disease history characteristics
      were not predictive for changes in sick leave in any of the groups. CONCLUSION:
      We conclude that adaptation to functional limitations played a major role in
      changes in sick leave in workers with asthma. Lung function characteristics
      hardly played a role.

PMID- 16001209
TI  - Use of cellular or cordless telephones and the risk for non-Hodgkin's lymphoma.
AB  - OBJECTIVES: To evaluate the use of cellular and cordless telephones as the risk
      factor for non-Hodgkin's lymphoma (NHL). METHODS: Male and female subjects aged
      18-74 years living in Sweden were included during a period from 1 December 1999
      to 30 April 2002. Controls were selected from the national population registry.
      Exposure to different agents was assessed by questionnaire. RESULTS: In total,
      910 (91%) cases and 1016 (92%) controls participated. NHL of the B-cell type was
      not associated with the use of cellular or cordless telephones. Regarding T-cell
      NHL and >5 year latency period, the use of analogue cellular phones yielded: odds
      ratio (OR) = 1.46, 95%; confidence interval (CI) = 0.58-3.70, digital: OR=1.92,
      95%; CI=0.77-4.80 and cordless phones: OR=2.47; CI=1.09-5.60. The corresponding
      results for certain, e.g. cutaneous and leukaemia, T-cell lymphoma for analogue
      phones were: OR=3.41, 95%; CI=0.78-15.0, digital: OR=6.12, 95%; CI=1.26-29.7 and
      cordless phones: OR=5.48, 95%; CI=1.26-23.9. CONCLUSIONS: The results indicate an
      association between T-cell NHL and the use of cellular and cordless telephones,
      however based on low numbers and must be interpreted with caution. Regarding B
      cell NHL no association was found.

PMID- 16001210
TI  - Relations between occupational, psychosocial and individual factors and three
      different categories of back disorder among supermarket workers.
AB  - OBJECTIVES: Up-to-date store-wide studies regarding low back pain (LBP) among
      supermarket/hypermarket workers are lacking. We investigated 12-month store-wide
      prevalence of different categories of LBP and possible associated biomechanical,
      individual/psychosocial risk factors across a large supermarket/hypermarket
      chain. METHODS: We performed a cross-sectional study of 3,702 subjects working in
      a group of small/medium-sized supermarkets (n=100) and large hypermarkets (n=7)
      belonging to a single chain in central-northern Italy applying established
      ergonomics/job-satisfaction policies. Data regarding the various departments were
      collected by a medical check-list, physical examination and questionnaire-all
      conducted by qualified physicians--and were analyzed in relation to a
      comprehensive biomechanical risk analysis. RESULTS: The overall 12-month
      prevalence of LBP in our sample (with a 82% response rate) was 34.5% (36.6% for
      females and 30.7% for males), with few differences being found between
      supermarkets and hypermarkets. Different types of LBP showed significant
      associations with stress-related psychosomatic symptoms, but not with job
      satisfaction (which was high). CONCLUSIONS: These encouraging data provide
      relevant information regarding workers operating in supermarkets/hypermarkets
      with an active commitment to ergonomic and job-satisfaction policies.

PMID- 16001211
TI  - Variation in the risk for liver and gallbladder cancers in socioeconomic and
      occupational groups in Sweden with etiological implications.
AB  - OBJECTIVES: To examine the associations between socioeconomic/occupational
      factors and liver cancer at various anatomic sites (including primary liver,
      gallbladder and other cancers). METHODS: We carried out a follow-up study on the
      economically active Swedish population, based on the Swedish Family-Cancer
      Database. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs)
      were calculated in different social classes and occupations. RESULTS: For primary
      liver cancer, farmers were at a decreased risk; increased risks were observed for
      male sales agents, journalists, seamen, waiters, cooks and female beverage
      manufacture workers. Similar patterns were observed for gallbladder cancer;
      workers employed as journalists, sales agents, cooks and stewards, and public
      safety workers showed increased risk. Only male transport workers showed
      increased risk of cancers in other parts. CONCLUSIONS: Occupations with high
      consumption of alcohol and/or high prevalence of smoking associated with a risk
      of liver and gallbladder cancers. The present study suggests that the effects of
      socioeconomic factors on liver cancer of different subsites are similar; alcohol
      drinking is a risk factor of gallbladder cancer because of the covariation of
      primary liver and gallbladder cancers in occupational groups.

PMID- 16001212
TI  - Urinary methoxyacetic acid as an indicator of occupational exposure to ethylene
      glycol dimethyl ether.
AB  - OBJECTIVE: To investigate whether methoxyacetic acid (MAA) is the metabolite of
      ethylene glycol dimethyl ether (EGdiME) in humans and whether its metabolite in
      urine can be used as a biomarker for exposure to EGdiME. METHODS: Workers
      occupationally exposed to EGdiME, as well as nonexposed controls, were studied.
      Urine samples were collected from 20 control subjects and, on Friday postshift,
      from 14 workers. The identification and quantification of the metabolite were
      performed by gas chromatography/mass spectrometry (GC/MS) and GC/FID,
      respectively. Air samples were collected on activated charcoal tubes by area
      sampling with battery-operated pumps. The glycol ether was analyzed by GC/FID.
      RESULTS: GC/MS clearly showed the metabolite of EGdiME to be MAA. Urinary MAA
      levels in the control subjects (background levels) were 0.0-0.3 mg/g crea. The
      levels of urinary MAA in the solvent-exposed workers were significantly
      (P<0.0001) higher than those in the control subjects. In the eight workers
      exposed to an average of 0.3 ppm of EGdiME and the six workers exposed to an
      average of 2.9 ppm, the mean urinary MAA level was 1.08 (range 0.6-1.5) mg/g crea
      and 9.33 (range 5.7-18.1) mg/g crea, respectively. These results can be explained
      by differences in the exposure intensity. CONCLUSIONS: Our results suggest that
      MAA is the metabolite of EGdiME, and that MAA in urine may be used for biological
      monitoring of EGdiME exposures.

PMID- 16001213
TI  - Occupational exposure to toluene and its possible causative role in renal damage
      development in shoe workers.
AB  - OBJECTIVES: An important, although, unprecise number of shoe workers in Leon,
      Mexico, are in continuous contact with toluene-based glues. The induction of
      renal glomerular and/or tubular lesions as a result of toluene exposure is still
      being discussed controversially. Our objective was to evaluate the extent of
      occupational exposure, assessing urinary o-Cresol excretion as a measure for
      toluene exposure in a population at risk as compared to a control population.
      Urinary albumin excretion (UAE) and N-acetyl-beta-D-glucosaminidase (NAG)
      enzymatic activity were tested to assess renal dysfunction. METHODS: A cross
      sectional study was performed comparing 50 toluene-exposed shoe workers and 25
      control subjects. Urinary o-cresol was assessed on first and last day of labor
      week from exposed subjects. A single urine sample was obtained from control
      subjects. Urinary Albumin excretion (UAE) and (NAG) activity were examined in 12
      h urine samples in all subjects. Urine and serum creatinine were measured to
      asses renal function. RESULTS: At the end of the labor week, urinary o-cresol
      levels were higher in samples obtained from exposed subjects. Albumin excretion
      was similar in the exposed and control groups. NAG activity was greater in the
      exposed group compared to control group (median 3.5 U/g creatinine vs 1.9 U/g
      creatinine, z=2.6, P=0.009). An inverse relationship was found between schooling
      years and the NAG enzymatic activity for the two studied groups (r= -0.27,
      P=0.02), CONCLUSIONS: Our findings support the hypothesis that toluene may be a
      factor associated with the presence of renal damage in exposed shoe workers. As
      NAG activity is increased, we believe the lesion initiates in the renal tubular
      cells.

PMID- 16001214
TI  - Stable isotopes in ecological studies.

PMID- 16001215
TI  - Spatial patterns and species performances in experimental plant communities.
AB  - Amongst the various hypotheses that challenged to explain the coexistence of
      species with similar life histories, theoretical, and empirical studies suggest
      that spatial processes may slow down competitive exclusion and hence promote
      coexistence even in the absence of evident trade-offs and frequent disturbances.
      We investigated the effects of spatial pattern and density on the relative
      importance of intra- and interspecific competition in a field experiment. We
      hypothesized that weak competitors increased biomass and seed production within
      neighborhoods of conspecifics, while stronger competitors would show increased
      biomass and seed production within neighborhoods of heterospecifics. Seeds of
      four annual plant species (Capsella bursa-pastoris, Stachys annua, Stellaria
      media, Poa annua) were sown in two spatial patterns (aggregated vs. random) and
      at two densities (low vs. high) in three different species combinations
      (monocultures, three and four species mixtures). There was a hierarchy in biomass
      production among the four species and C. bursa-pastoris and S. media were among
      the weak competitors. Capsella and Stellaria showed increased biomass production
      and had more individuals in the aggregated compared to the random pattern,
      especially when both superior competitors (S. annua, P. annua) were present. For
      P. annua we observed considerable differences among species combinations and
      unexpected pattern effects. Our findings support the hypothesis that weak
      competitors increase their fitness when grown in the neighborhood of
      conspecifics, and suggested that for the weakest competitors the species identity
      is not important and all other species are best avoided through intraspecific
      aggregation. In addition, our data suggest that the importance of spatial pattern
      for the other competitors might not only depend on the position within the
      hierarchy but also on the identity of neighbor species, species characteristics,
      below ground interactions, and other nonspatial factors.

PMID- 16001216
TI  - Movement of carbon among estuarine habitats and its assimilation by
      invertebrates.
AB  - We measured the extent of movement of carbon and its assimilation by
      invertebrates among estuarine habitats by analysing carbon stable isotopes of
      invertebrates collected along transects crossing the boundary of two habitats.
      The habitats were dominated by autotrophs with distinct isotope values: (1)
      mudflats containing benthic microalgae (mean -22.6, SE 0.6 per thousand) and (2)
      seagrass and its associated epiphytic algae (similar values, pooled mean -9.8,
      0.5 per thousand). Three species of invertebrates were analysed: a palaemonid
      shrimp, Macrobrachium intermedium, and two polychaete worms, Nephtys
      australiensis and Australonereis ehlersi. All species had a similar narrow range
      of isotope values (-9 to -14 per thousand), and showed no statistically
      significant relationship between position along transect and isotope values.
      Animals were relying on carbon from seagrass meadows whether they were in
      seagrass or on mudflats hundreds of metres away. Particulate organic matter
      collected from superficial sediments along the transects had similar values to
      animals (mean -11.1, SE 1.3 per thousand) and also showed no significant
      relationship with position. The isotope values of these relatively immobile
      invertebrates and the particulate detritus suggest that carbon moves from
      subtidal seagrass meadows to mudflats as particulate matter and is assimilated by
      invertebrates. This assimilation might be direct in the case of the detritivorous
      worm, A. ehlersi, but must be via invertebrate prey in the case of the
      carnivorous worm, N. australiensis and the scavenging shrimp, M. intermedium. The
      extent of movement of carbon among habitats, especially towards shallower
      habitats, is surprising since in theory, carbon is more likely to move offshore
      in situations such as the current study where habitats are in relatively open,
      unprotected waters.

PMID- 16001217
TI  - The interacting effects of elevated atmospheric CO2 concentration, drought and
      leaf-to-air vapour pressure deficit on ecosystem isoprene fluxes.
AB  - Isoprene is the most abundant biogenic hydrocarbon released from vegetation and
      it plays a major role in tropospheric chemistry. Because of its link to climate
      change, there is interest in understanding the relationship between CO2, water
      availability and isoprene emission. We explored the effect of atmospheric
      elevated CO2 concentration and its interaction with vapour pressure deficit (VPD)
      and water stress, on gross isoprene production (GIP) and net ecosystem exchange
      of CO2 (NEE) in two Populus deltoides plantations grown at ambient and elevated
      atmospheric CO2 concentration in the Biosphere 2 Laboratory facility. Although
      GIP and NEE showed a similar response to light and temperature, their responses
      to CO2 and VPD were opposite; NEE was stimulated by elevated CO2 and depressed by
      high VPD, while GIP was inhibited by elevated CO2 and stimulated by high VPD. The
      difference in response between isoprene production and photosynthesis was also
      evident during water stress. GIP was stimulated in the short term and declined
      only when the stress was severe, whereas NEE started to decrease from the
      beginning of the experiment. This contrasting response led the carbon lost as
      isoprene in both the ambient and the elevated CO2 treatments to increase as water
      stress progressed. Our results suggest that water limitation can override the
      inhibitory effect of elevated CO2 leading to increased global isoprene emissions
      in a climate change scenario with warmer and drier climate.

PMID- 16001218
TI  - Connecting plant-microbial interactions above and belowground: a fungal endophyte
      affects decomposition.
AB  - Mutualisms can strongly affect the structure of communities, but their influence
      on ecosystem processes is not well resolved. Here we show that a plant-microbial
      mutualism affects the rate of leaf litter decomposition using the widespread
      interaction between tall fescue grass (Lolium arundinaceum) and the fungal
      endophyte Neotyphodium coenophialum. In grasses, fungal endophytes live
      symbiotically in the aboveground tissues, where the fungi gain protection and
      nutrients from their host and often protect host plants from biotic and abiotic
      stress. In a field experiment, decomposition rate depended on a complex
      interaction between the litter source (collected from endophyte-infected or
      endophyte-free plots), the decomposition microenvironment (endophyte-infected or
      endophyte-free plots), and the presence of mesoinvertebrates (manipulated by the
      mesh size of litter bags). Over all treatments, decomposition was slower for
      endophyte-infected fescue litter than for endophyte-free litter. When
      mesoinvertebrates were excluded using fine mesh and litter was placed in a
      microenvironment with the endophyte, the difference between endophyte-infected
      and endophyte-free litter was strongest. In the presence of mesoinvertebrates,
      endophyte-infected litter decomposed faster in microenvironments with the
      endophyte than in microenvironments lacking the endophyte, suggesting that plots
      differ in the detritivore assemblage. Indeed, the presence of the endophyte in
      plots shifted the composition of Collembola, with more Hypogastruridae in the
      presence of the endophyte and more Isotomidae in endophyte-free plots. In a
      separate outdoor pot experiment, we did not find strong effects of the litter
      source or the soil microbial/microinvertebrate community on decomposition, which
      may reflect differences between pot and field conditions or other differences in
      methodology. Our work is among the first to demonstrate an effect of plant
      endophyte mutualisms on ecosystem processes under field conditions.

PMID- 16001219
TI  - Using stable isotopes to study resource acquisition and allocation in
      procellariiform seabirds.
AB  - Some procellariiform seabirds use a dual strategy for provisioning their chicks
      by alternating short (ST) and long (LT) foraging trips. Parent birds gain mass
      during LT but they lose mass while increasing the chick feeding frequency during
      ST. Self-feeding during LT is crucial for the success of ST because firstly most
      of the energy used during ST is likely to be derived from the energy stored
      during LT and secondly self-feeding during ST is presumed to be negligible. Self
      feeding by adult procellariiforms is thus a key issue to understand allocation
      processes but it is still poorly known. We tested these predictions by using the
      stable isotope (delta(15)N and delta(13)C) technique on birds' plasma and prey
      with the short-tailed shearwater Puffinus tenuirostris breeding at Tasmania as a
      model. Parent shearwaters returning to the colony after a LT have an
      Antarctic/subantarctic delta(13)C signature in their plasma (-23.8 per thousand),
      thus indicating that they fed in cold waters, far away from their breeding
      colony, for their own maintenance. Parent birds returning to the colony after a
      ST also have a distant Antarctic/subantarctic delta(13)C signature in their
      plasma (-24.3 per thousand), thus verifying that self-feeding is negligible
      during ST and that birds fast at that time, using energy stores built up in cold
      waters. Plasma delta(15)N values of adults (8.8 per thousand) indicates they
      mainly prey upon zooplankton-eating organisms, probably mesopelagic myctophid
      fishes. A simple isotopic mixing model estimates that they consume by mass 87%
      myctophids and 13% subantarctic krill when self-feeding. Finally and as expected,
      the carbon isotopic signature of chick plasma (-22.2 per thousand) was
      intermediate between those of high- and low-latitude marine organisms and is thus
      in agreement with chicks being fed with a large diversity of prey species caught
      by adult birds from Antarctic to Tasmanian waters. One main consequence of this
      system is that reproduction of a Tasmanian species is controlled by resources
      available at great distances from the breeding colony that drive allocation
      decisions of parent birds.

PMID- 16001220
TI  - Summer water use by California coastal prairie grasses: fog, drought, and
      community composition.
AB  - Plants in the Mediterranean climate region of California typically experience
      summer drought conditions, but correlations between zones of frequent coastal fog
      inundation and certain species' distributions suggest that water inputs from fog
      may influence species composition in coastal habitats. We sampled the stable H
      and O isotope ratios of water in non-photosynthetic plant tissue from a variety
      of perennial grass species and soil in four sites in northern California in order
      to determine the proportion of water deriving from winter rains and fog during
      the summer. The relationship between H and O stable isotopes from our sample
      sites fell to the right of the local meteoric water line (LMWL) during the summer
      drought, providing evidence that evaporation of water from the soil had taken
      place prior to the uptake of water by vegetation. We developed a novel method to
      infer the isotope values of water before it was subjected to evaporation in which
      we used experimental data to calculate the slope of the deltaH versus deltaO line
      versus the LMWL. After accounting for evaporation, we then used a two-source
      mixing model to evaluate plant usage of fog water. The model indicated that 28
      66% of the water taken up by plants via roots during the summer drought came from
      fog rather than residual soil water from winter rain. Fog use decreased as
      distance from the coast increased, and there were significant differences among
      species in the use of fog. Rather than consistent differences in fog use by
      species whose distributions are limited to the coast versus those with broader
      distributions, species responded individualistically to summer fog. We conclude
      that fogwater inputs can mitigate the summer drought in coastal California for
      many species, likely giving an advantage to species that can use it over species
      that cannot.

PMID- 16001221
TI  - Niche overlap estimates based on quantitative functional traits: a new family of
      non-parametric indices.
AB  - The concept of niche overlap appears in studies of the mechanisms of the
      maintenance of species diversity, in searches for assembly rules, and in
      estimation of within-community species redundancy. For plant traits measured on a
      continuous scale, existing indices are inadequate because they split the scale
      into a number of categories thus losing information. An index is easy to
      construct if we assume a normal distribution for each trait within a species, but
      this assumption is rarely true. We extend and apply an index, NO(K), which is
      based on kernel density functions, and can therefore work with distributions of
      any shape without prior assumptions. For cases where the ecologist wishes to
      downweight traits that are inter-correlated, we offer a variant that does this:
      NO(Kw). From either of these indices, an index of the mean niche overlap in a
      community can be calculated: NO(K,community) and NO(Kw,community). For all these
      indices, the variance can be calculated and formulae for this are given. To give
      examples of the new indices in use, we apply them to a coastal fish dataset and a
      sand-dune plant dataset. The former exhibits considerable non-normality,
      emphasising the need for kernel-based indices. Accordingly, there was a
      considerable difference in index values, with those for an index based on a
      normal distribution being significantly higher than those from an index which,
      being based on kernel fitting, is not biased by an assumption for the
      distribution. The NO(K) values were ecologically consistent for the fish species
      concerned, varying from 0.02 to 0.53. The sand-dune plant data also showed a wide
      range of overlap values. Interestingly, the least overlap was between two
      graminoids, which would have been placed in the same functional group in the
      coarse classification often used in functional-type/ecosystem-function work.

PMID- 16001222
TI  - A reanalysis of the body mass scaling of trampling by large herbivores.

PMID- 16001223
TI  - Foragers versus farmers: contrasting effects of two behavioural groups of
      herbivores on coral reefs.
AB  - Herbivorous fishes have been attributed a central role in structuring benthic
      communities on coral reefs. However, the relative importance of different
      behavioural groups of herbivores may differ and their interactions may be
      complex. This study focuses on an experiment that discriminates between two
      groups of herbivorous fish: (1) "Foragers" (relatively mobile, schooling grazers,
      including parrotfishes and surgeonfishes) and (2) "Farmers" (highly site
      attached, territorial species, primarily damselfishes). Preliminary observations
      at Kimbe Bay (Papua New Guinea) showed that both groups were common, and that
      farmers defended areas from foragers and maintained algal communities that were
      distinct from the surrounding undefended substratum. An orthogonal combination of
      a farmer removal treatment and a forager exclusion treatment was applied to
      isolate their separate effects on algae and corals, and to determine whether
      farmer territory composition results from forager exclusion or algal cultivation.
      The experiment showed that foragers had quantitatively greater and qualitatively
      different effects on sessile benthic community structure than farmers. Where
      foragers were excluded, there were substantial increases in the cover and biomass
      of macro-algae and a decline in some corals, regardless of the presence of
      farmers. Where farmers were removed there was a moderate decline in the cover of
      some food algal species, regardless of whether foragers had access. No effect of
      the exclusion of foragers by farmers could be detected. Our results support
      prevailing views that foragers have a major impact on coral reefs and farmers
      cultivate selected algae, but challenge the hypothesis that damselfish influence
      habitat structure by moderating forager disturbance.

PMID- 16001224
TI  - Pulse additions of soil carbon and nitrogen affect soil nitrogen dynamics in an
      arid Colorado Plateau shrubland.
AB  - Biogeochemical cycles in arid and semi-arid ecosystems depend upon the ability of
      soil microbes to use pulses of resources. Brief periods of high activity
      generally occur after precipitation events that provide access to energy and
      nutrients (carbon and nitrogen) for soil organisms. To better understand pulse
      driven dynamics of microbial soil nitrogen (N) cycling in an arid Colorado
      Plateau ecosystem, we simulated a pulsed addition of labile carbon (C) and N in
      the field under the canopies of the major plant species in plant interspaces.
      Soil microbial activity and N cycling responded positively to added C while NH
      (4) (+) -N additions resulted in an accumulation of soil NO (3) (-) . Increases
      in microbial activity were reflected in higher rates of respiration and N
      immobilization with C addition. When both C and N were added to soils, N losses
      via NH(3) volatilization decreased. There was no effect of soil C or N
      availability on microbial biomass N suggesting that the level of microbial
      activity (respiration) may be more important than population size (biomass) in
      controlling short-term dynamics of inorganic and labile organic N. The effects of
      C and N pulses on soil microbial function and pools of NH (4) (+) -N and labile
      organic N were observed to last only for the duration of the moisture pulse
      created by treatment addition, while the effect on the NO (3) (-) -N pool
      persisted after soils dried to pre-pulse moisture levels. We observed that
      increases in available C lead to greater ecosystem immobilization and retention
      of N in soil microbial biomass and also lowered rates of gaseous N loss. With the
      exception of trace gas N losses, the lack of interaction between available C and
      N on controlling N dynamics, and the subsequent reduction in plant available N
      with C addition has implications for the competitive relationships between plants
      species, plants and microbes, or both.

PMID- 16001225
TI  - Dietary specialization influences the efficacy of larval tortoise beetle shield
      defenses.
AB  - Plant chemical defenses and escape from natural enemies have been postulated to
      select for dietary specialization in herbivorous insects. In field and laboratory
      bioassays, we evaluated the effectiveness of intact and chemically modified
      larval shield defenses of the generalist Chelymorpha alternans and the
      specialists Acromis sparsa and Stolas plagiata (Chrysomelidae: Cassidinae)
      against three natural predators, using larvae reared on two morning glory
      (Convolvulaceae) species. We assessed whether: (1) specialists were better
      defended than generalists when both were fed and assayed on the same plant; (2)
      larval shield defenses were chemical, physical, or both; and (3) specialists
      exploit chemistry better than generalists. Live specialist larvae survived at
      higher rates than did generalists in predator bioassays with the bug Montina
      nigripes (Reduviidae), but there were no differences among groups against two
      species of Azteca ants (Hymenoptera: Dolichoderinae). Solvent leaching by H(2)O
      or MeOH significantly reduced shield efficacy for all species compared to larvae
      with intact shields. In contrast, freshly killed specialist larvae exhibited
      significantly lower capture rates and frequencies than the generalists. Although
      solvent leaching significantly reduced overall shield efficacy for freshly killed
      larvae of all species, the pattern of leaching effects differed between
      specialists and generalists, with H(2)O-leaching having a greater impact on the
      specialists. The overall vulnerability of the generalists appears due to lower
      chemical protection, which is ameliorated by increased escape behaviors,
      suggesting a selective trade-off between these defensive components. These
      experiments indicate that shield defenses are essential for larval survival and
      that specialists are superior at exploiting plant compounds residing in the
      aqueous fraction. Our results support the hypothesis that diet-specialized
      herbivorous insects have more effective defenses than generalists when both feed
      on the same plant due to the differential ability to exploit defensive precursors
      obtained from the host. The evolution of dietary specialization may therefore
      confer the advantage of enhanced enemy-free space.

PMID- 16001226
TI  - Costs and limits of dosage response to predation risk: to what extent can
      tadpoles invest in anti-predator morphology?
AB  - Inducible defences have long been considered as a polyphenism opposing defended
      and undefended morphs. However, in nature, preys are exposed to various levels of
      predation risk and scale their investment in defence to actual predation risk.
      Still, among the traits that are involved in the defence, some are specific to
      one predator type while others act as a more generalised defence. The existence
      of defence costs could prevent an individual investing in all these traits
      simultaneously. In this study, we investigate the impact of an increasing level
      of predator density (stickleback, Gasterosteus aculeatus) on the expression of
      morphological inducible defences in tadpoles of Rana dalmatina. In this species,
      investment in tail length and tail muscle is a stickleback-specific response
      while increased tail fin depth is a more general defence. As expected, we found a
      relationship between investment in defence and level of risk through the
      responses of tail fin depth and tail length. We also found an exponential
      increase of defence cost, notably expressed by convex decrease of growth and
      developmental rates. We found a relative independence of investment in the
      different traits that compose the defence, revealing a high potential for fine
      tuning the expression of defended phenotypes with respect to local ecological
      conditions.

PMID- 16001227
TI  - The many faces of population density.
AB  - Population density, one of the most fundamental demographic attributes, may vary
      systematically with spatial scale, but this scale-sensitivity is incompletely
      understood. We used a novel approach-based on fully censused and mapped
      distributions of eastern grey squirrel (Sciurus carolinensis) dreys, beaver
      (Castor canadensis) lodges, and moose (Alces alces)--to explore the scale
      dependence of population density and its relationship to landscape features. We
      identified population units at several scales, both objectively, using cluster
      analysis, and arbitrarily, using artificial bounds centred on high-abundance
      sites. Densities declined with census area. For dreys, this relationship was
      stronger in objective versus arbitrary population units. Drey density was
      inconsistently related to patch area, a relationship that was positive for all
      patches but negative when non-occupied patches were excluded. Drey density was
      negatively related to the proportion of green-space and positively related to the
      density of buildings or roads, relationships that were accentuated at coarser
      scales. Mean drey densities were more sensitive to scale when calculated as
      organism-weighted versus area-weighted averages. Greater understanding of these
      scaling effects is required to facilitate comparisons of population density
      across studies.

PMID- 16001228
TI  - Mechanical frequency and stimulation-site-related differences in vibrotactile
      detection capacity along the lip vermilion in young adults.
AB  - Accurate clinical assessment of the infraorbital and mental branch of the
      trigeminal nerve is aided by an appreciation of the variations in sensitivity
      that may exist along the surface of the perioral region under examination. The
      purpose of this investigation was to map the mediolateral spatial and frequency
      variations in vibrotactile detection capacity to inputs delivered to the upper
      lip (UL) and lower lip (LL) vermilion. Mechanical vibrotactile inputs at
      frequencies of 5, 10, 50, and 150 Hz were delivered to three locations on the
      vermilion of the UL and LL: midsagittally and laterally (left and right) at a
      point halfway between the midsagittal plane and the oral angle. An adapted
      staircase tracking method was used to converge upon a threshold value for each
      test frequency at each stimulation site. The results indicated that midsagittal
      vermilion sites were significantly more sensitive to our range of vibrotactile
      inputs compared to lateral vermilion locations. In addition, no significant
      differences in sensitivity as a function of laterality or between the UL and LL
      vermilion sites were noted. Greater midline sensitivity to vibrotactile
      stimulation suggests that receptive fields at this location may be of greater
      density and/or demonstrate greater overlap compared to lateral vermilion sites.

PMID- 16001229
TI  - [Incomplete tonsure like alopecia].

PMID- 16001231
TI  - Low concentrations of aggregated beta-amyloid induce neurite formation via the
      neurotrophin receptor p75.
AB  - Aggregated beta-amyloid (Abeta) binds to the neurotrophin receptor p75 and
      induces signaling. We examined this signaling process in different cell lines
      which express p75 either naturally (Schwannoma RN22 cells) or which are stably
      transfected with wild-type p75 (MDCKwt and PCNA cells) or with a truncated form
      of p75 comprising only extracellular and transmembrane domains (MDCKtm cells).
      While Abeta in higher concentrations (10-100 microM) is known to cause apoptosis
      via p75, our experiments focused on the effects of low concentrations of Abeta
      (25 nM) which may occur in early stages of Alzheimer disease. Application of
      Abeta caused tyrosine phosphorylation of wild-type p75 and induced the Ras-ERK
      pathway as has been reported for nerve growth factor (NGF). Since Ras activation
      and ERK phosphorylation (via MEK) could not be observed in MDCKtm cells and since
      they were clearly reduced in cells transfected with a p75 antisense construct,
      these effects should have been mediated by p75. Abeta also induced Ras and ERK
      activation in cerebellar neurons of 2-day-old rats which express p75 at that
      developmental stage but not TrkA; other Trk receptors were inhibited by K252a. In
      these neurons, Abeta led to quick formation, branching and elongation of
      processes. But while NGF distinctly promoted neurite branching and elongation,
      Abeta was less effective in neurite elongation and counts of small processes and
      of growth cones remained clearly elevated after 24-h stimulation; these
      peculiarities might be linked to aberrant neuronal connections reported for an
      animal model of Alzheimer disease. Essentially, the observed effects were
      mediated by interaction of Abeta and p75.

PMID- 16001232
TI  - Interstitial fluid glucose dynamics during insulin-induced hypoglycaemia.
AB  - AIMS/HYPOTHESIS: Glucose sensors often measure s.c. interstitial fluid (ISF)
      glucose rather than blood or plasma glucose. Putative differences between plasma
      and ISF glucose include a protracted delay during the recovery from hypoglycaemia
      and an increased gradient during hyperinsulinaemia. These have often been
      investigated using sensor systems that have delays due to signal smoothing, or
      require long equilibration times. The aim of the present study was to define
      these relationships during hypoglycaemia in a well-equilibrated system with no
      smoothing. METHODS: Hypoglycaemia was induced by i.v. insulin infusion (360
      pmol.m(-2).min(-1)) in ten non-diabetic subjects. Glucose was sequentially
      clamped at approximately 5, 4.2 and 3.1 mmol/l and allowed to return to
      normoglycaemia. Subjects wore two s.c. glucose sensors (Medtronic MiniMed,
      Northridge, CA, USA) that had been inserted for more than 12 h. A two-compartment
      model was used to quantify the delay and gradient. RESULTS: The delay during the
      fall in plasma glucose was not different from the delay during recovery (8.3+/
      0.67 vs 6.3+/-1.1 min; p=0.27) and no differences were observed in the ratio of
      sensor current to plasma glucose at basal insulin (2.7+/-0.25 nA.mmol(-1).l)
      compared with any of the hyperinsulinaemic clamp phases (2.8+/-0.18, 2.7+/-0.021,
      2.9+/-0.21; p=NS). The ratio was significantly elevated following recovery to
      normoglycaemia (3.1+/-0.2 nA.mmol(-1).l; p<0.001). CONCLUSIONS/INTERPRETATION:
      The elevated ratio suggests that the plasma to ISF glucose gradient was decreased
      following hypoglycaemia, possibly due to increased skin blood flow. Recovery from
      hypoglycaemia is not accompanied by a protracted delay and insulin does not
      increase the plasma to s.c. ISF glucose gradient.

PMID- 16001233
TI  - Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma
      agonist, dose-dependently improves the metabolic abnormalities associated with
      insulin resistance in a non-diabetic population.
AB  - AIMS/HYPOTHESIS: Insulin resistance is associated with abnormalities in lipid and
      glucose metabolism, which are major components of metabolic syndrome and risk
      factors for vascular disease. This study examined the effect of tesaglitazar
      (Galida), a novel, dual-acting peroxisome proliferator-activated receptor
      alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of
      insulin resistance. METHODS: A 12-week, multicentre, randomised, double-blind,
      placebo-controlled, dose-finding study compared the efficacy and safety of oral
      tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic
      patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7
      mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for
      women). RESULTS: A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the
      primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by
      15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%;
      p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001). At
      the end of treatment there was a dose-dependent increase in patients with pattern
      A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0
      mg). Tesaglitazar produced significant reductions in fasting insulin
      concentration (-35%; p<0.0001) and plasma glucose concentration (-0.47 mmol/l;
      p<0.0001). Respiratory infection and gastrointestinal symptoms were the most
      common adverse events and were similarly frequent in all groups.
      CONCLUSIONS/INTERPRETATION: Tesaglitazar was well tolerated and produced
      significant, dose-dependent improvements in lipid and glucose metabolism and
      insulin sensitivity. Tesaglitazar may have the potential to prevent vascular
      complications and delay progression to diabetes in these patients.

PMID- 16001234
TI  - Is there really an epidemic of diabetes?

PMID- 16001236
TI  - Contact-angle, ellipsometric, and spin-diffusion solid-state nuclear magnetic
      resonance spectroscopic investigations of copolymeric stationary phases
      immobilized on SiO2 surfaces.
AB  - SiO2 surfaces-silica gel particles and silica wafers-were modified by covalently
      immobilizing three poly(ethylene-co-acrylic acid) copolymers, (-CH2CH2
      )x[CH2CH/(CO2H)-]y, with different chain lengths and mass fractions of acrylic
      acid. 13C solid-state NMR spectroscopy on the modified silica gel particles
      revealed both mobile gauche and rigid trans aligned alkyl chains in the
      copolymers. For copolymers attached to silica wafers via a 3
      aminopropyltriethoxysilane spacer molecule, ellipsometric measurements revealed a
      mean value of the layer thickness distribution of 6.5 and 4.3 nm, respectively,
      for the more acidic and the shorter copolymers with mobile alkyl chains mostly in
      the gauche conformation. For the longest and least acidic copolymer with more
      rigid trans ordered alkyl chains, however, a mean phase thickness of 10.6 nm was
      found. When this copolymer was immobilized via a 3
      glycidoxypropyltrimethoxysilane spacer molecule we measured a mean layer
      thickness of 9.9 nm. A model of the surface morphology of this immobilization
      strategy was derived using spin-diffusion 13C NMR measurements on the
      corresponding modified silica. It was thereby proven that the trans and gauche
      aligned alkyl chains occur in distinct domains of certain sizes on the silica
      surface. The surface polarity of all modified silica wafers was also investigated
      by measurement of contact-angle.

PMID- 16001235
TI  - Expression and secretion of alpha1-proteinase inhibitor are regulated by
      proinflammatory cytokines in human pancreatic islet cells.
AB  - AIMS/HYPOTHESIS: Alpha1-proteinase inhibitor (alpha1-PI) has been considered a
      key player in inflammatory processes. In humans, the main production site of
      alpha1-PI is the liver, but other tissues, including pancreatic islets, also
      synthesise this molecule. The aims of this study were to assess the islet cell
      types that produce alpha1-PI, to determine whether alpha1-PI is actually secreted
      by islet cells, and to assess how its production and/or secretion are regulated.
      METHODS: Expression of alpha1-PI in human islet cells was assessed by
      immunofluorescence, electron microscopy and western blotting. Release of alpha1
      PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of
      cytokines on alpha1-PI synthesis and secretion were tested. RESULTS:
      Immunofluorescence showed that alpha and delta cells do express alpha1-PI,
      whereas beta cells do not. By electron microscopy, we demonstrated a
      colocalisation of alpha1-PI with glucagon and somatostatin within secretory
      granules. Immunolabelling also revealed localisation of alpha1-PI within the
      Golgi apparatus, related vesicles and lysosomal structures. The expression of
      alpha1-PI in islet cells was also demonstrated by western blotting and ELISA of
      protein extracts. ELISA and reverse haemolytic plaque assay showed that alpha1-PI
      is secreted into the culture medium. Treatment of islet cells with IL-1beta and
      oncostatin M for 4 days increased the production and release of alpha1-PI.
      CONCLUSIONS/INTERPRETATION: Our results demonstrate that alpha1-PI is expressed
      by the alpha and delta cells of human islets, and that proinflammatory cytokines
      enhance the production and release of this inhibitor.

PMID- 16001237
TI  - Fully automated multianalyte determination of different classes of pesticides, at
      picogram per litre levels in water, by on-line solid-phase extraction-liquid
      chromatography-electrospray-tandem mass spectrometry.
AB  - This paper reports the development of a fully automated method for the
      multianalyte determination of twenty pesticides belonging to different classes
      (triazines, phenylureas, organophosphates, anilines, acidic, propanil, and
      molinate) in natural and treated waters. The method, based on on-line solid-phase
      extraction-liquid chromatography-electrospray-tandem mass spectrometry, is highly
      sensitive (limits of detection between 0.004 and 2.8 ng L(-1)), precise (relative
      standard deviations between 2.0 and 12.1%), reliable (two selected reaction
      monitoring transitions are monitored per compound), rapid (45 min per sample),
      and simple. The application of this method to the monitoring of the target
      compounds in a waterworks revealed the presence of the pesticides investigated at
      concentrations up to 516 and 82 ng L(-1) (total pesticide concentration) in river
      water and ground water, respectively, used as sources, and their gradual removal
      through the purification process.

PMID- 16001238
TI  - Quantification of phytochelatins in plants by reversed-phase HPLC-ESI-MS-MS.
AB  - An on-line HPLC-ESI-MS-MS method has been developed for determination of
      glutathione and phytochelatins (PC) in plant tissues. For sample pretreatment,
      dithiothreitol (DTT) must be added at the very beginning, as an anti-oxidant.
      Optimization of instrumental conditions i.e. composition of HPLC mobile phase,
      ionization efficiency of the electrospray interface, and MS-MS detection in the
      multiple ion-monitoring mode, are the central aspects of this work. A polystyrene
      packed column was found to be superior to a standard silica-packed reversed-phase
      column. A concave quadratic gradient of ammonium formate buffer and acetonitrile
      was found to be optimum. The limits of quantitation were 0.2 micromol kg(-1)
      plant tissue for glutathione and PC. The method has been applied to analysis of
      tissue samples from Vicia faba grown in Cd-containing nutrient solutions.

PMID- 16001239
TI  - Electroanalytical method for determination of the pesticide dichlorvos using gold
      disk microelectrodes.
AB  - This paper reports the use of laboratory-prepared gold microelectrodes and square
      wave voltammetry for analytical determination of low concentrations of the
      pesticide dichlorvos in pure and natural water samples. After optimization of the
      experimental and voltammetric conditions, the best voltammetric responses-current
      intensity and voltammetric profile-were obtained in 0.1 mol L(-1) NaClO4 with
      f=100 s(-1), a=50 mV, and DeltaE(s)=2 mV. The observed detection and
      quantification limits in pure water were 7.8 and 26.0 microg L(-1), respectively.
      The reproducibility and repeatability of the method were also determined; the
      results were 1.4% (n=5) and 1.2% (n=10), respectively. Possible interfering
      effects were evaluated in natural water samples collected at different points
      with different levels of contamination from agricultural, domestic, or industrial
      waste from an urban stream. Results showed that the detection and quantification
      limits increased as a function of the quantity of organic matter present in the
      samples. Nonetheless, the values observed for these method characteristics were
      below the maximum value allowed by the Brazilian code for organophosphorus
      pesticides in water samples. Recovery curves constructed using the standard
      addition method were shown to be satisfactory compared with those obtained from
      high-performance liquid chromatography, confirming the suitability of the method
      for analysis of natural water samples. Finally, when the method was used to
      determine dichlorvos in spiked cows' milk samples, satisfactory recovery and
      relative standard deviations were obtained.

PMID- 16001240
TI  - Sample introduction assisted by compressed air in flame furnace AAS: a simple and
      sensitive method for the determination of traces of toxic elements.
AB  - The power of detection of flame AAS for the toxic elements Cd, Hg, Pb and Tl can
      be improved by 1-2 orders of magnitude by using flame furnace AAS. In flame
      furnace AAS, liquid samples are introduced directly into a nickel tube located in
      the flame, in the simplest case through a ceramic thermospray capillary.
      Transportation of the samples is achieved by using compressed air only.
      Comparatively low detection limits are achieved by both beam injection flame
      furnace (BIFF-AAS) and thermospray flame furnace AAS (TS-FF-AAS). For TS-FF-AAS,
      a pressure of less than 20 kPa (<80 in. water) is required. The TS-FF-AAS
      technique is very simple, robust and cheap. The detection limits were 0.2-0.4
      microg L(-1) (Cd), 40-100 microg L(-1) (Hg), 5-9 microg L(-1) (Pb) and 4-14
      microg L(-1) (Tl), respectively, depending on the method, flow rate and sample
      volume used. Pb and Cd were found at concentrations of 0.1-2 and 0.005-0.3 microg
      g(-1), respectively, in samples of various spices.

PMID- 16001241
TI  - 3D roadmap in neuroangiography: technique and clinical interest.
AB  - We present the first clinical results obtained with a novel technique: the three
      dimensional [3D] roadmap. The major difference from the standard 2D digital
      roadmap technique is that the newly developed 3D roadmap is based on a rotational
      angiography acquisition technique with the two-dimensional [2D] fluoroscopic
      image as an overlay. Data required for an accurate superimposition of the
      previously acquired 3D reconstructed image on the interactively made 2D
      fluoroscopy image, in real time, are stored in the 3D workstation and constitute
      the calibration dataset. Both datasets are spatially aligned in real time; thus,
      the 3D image is accurately superimposed on the 2D fluoroscopic image regardless
      of any change in C-arm position or magnification. The principal advantage of the
      described roadmap method is that one contrast injection allows the C-arm to be
      positioned anywhere in the space and allows alterations in the distance between
      the x-ray tube and the image intensifier as well as changes in image
      magnification. In the clinical setting, the 3D roadmap facilitated intravascular
      neuronavigation with concurrent reduction of procedure time and use of contrast
      medium.

PMID- 16001242
TI  - Liver transplantation after stem cell transplantation with the same living donor
      in a monozygotic twin with acute myeloid leukemia.
AB  - Two monozygotic twins from a Swedish, nonconsanguine family-with concordant acute
      myeloid leukemia and similar morphological and cytogenetic changes, but with
      additional changes in one twin, suggestive of clonal evolution-are described.
      Twin I relapsed 4 months after completion of treatment, while twin II was still
      on treatment and was transplanted with stem cells from the human leukocyte
      antigen-identical father. An early relapse after transplantation was treated with
      donor lymphocyte infusions, but twin I relapsed again and died 8 months after
      stem cell transplantation (SCT). On relapse of twin I, treatment of twin II was
      reconsidered and consolidation was intensified with SCT in CR1 with peripheral
      blood stem cells from the father. Due to irreversible liver failure caused by
      severe venoocclusive disease, a living, related liver transplantation from the
      father was performed on day +84 post-SCT. Minimal immunosuppression was required,
      and graft rejection did not occur. The patient was in complete remission 29
      months after SCT and 25 months after liver transplantation.

PMID- 16001243
TI  - High-dose melphalan is an effective salvage therapy in acute myeloid leukaemia
      patients with refractory relapse and relapse after autologous stem cell
      transplantation.
AB  - In a pilot study high-dose melphalan (HD-Mel, 200 mg/m2) and autologous stem cell
      transplantation (ASCT) were administered to 14 patients (median age 52, range 29
      60 years) with acute myeloid leukaemia (AML) in first relapse after a previous
      ASCT in first complete remission (n=11) or chemotherapy (n=3). A first cohort of
      five patients received HD-Mel as salvage therapy after a previous cycle of
      mitoxantrone, topotecan and cytarabine (MTC) had failed in four out of five
      patients, while a second cohort of nine patients received HD-Mel in untreated
      relapse. Thirteen (93%) of 14 patients achieved a second complete remission
      (CR2), including all four patients who had been refractory to MTC. No treatment
      related mortality was observed after HD-Mel. Thirteen (93%) patients were able to
      proceed to a dose-reduced allogeneic stem cell transplantation (allo-SCT) from
      human-leucocyte-antigens-compatible unrelated (n=12) or sibling donors (n=1) in
      CR2 (n=11) or poor recovery/relapse (n=2) after a median of 2 (1.7-4.5) months
      following HD-Mel. Three MTC-refractory patients, but none of the upfront HD-Mel
      patients, died due to an allograft-related non-relapse cause. Nine patients are
      alive in CR2 after a median of 6 (2-49) months after HD-Mel and a median of 4
      (0.6-47) months after a sequential allo-SCT. Although median follow-up is still
      short, the proportion of patients achieving a CR2, as well as of those proceeding
      to a subsequent reduced-intensity-conditioning-allo-SCT, is superior to those
      previously reported. Our results highly encourage to further investigate HD-Mel
      and ASCT as a promising salvage regimen for relapsed AML patients for whom
      autologous peripheral blood stem cells are available.

PMID- 16001244
TI  - Mycophenolate mofetil for the treatment of acute and chronic steroid-refractory
      graft-versus-host disease.
AB  - Corticosteroid-resistant graft-versus-host disease (GvHD) is difficult to manage
      and is associated with high morbidity and mortality. The purpose of our study was
      to evaluate the safety and efficacy of mycophenolate mofetil (MMF) as the salvage
      therapy for steroid-refractory GvHD. Twenty one patients (10 with acute GvHD and
      11 with chronic GvHD) were studied retrospectively. Steroid-resistant GvHD was
      defined as acute or chronic GvHD not responding to a first-line regimen of
      cyclosporine A and corticosteroids in a dose equivalent to 2 mg/kg
      methylprednisolone for at least 7 days. MMF was added at a dose of 2 g daily, and
      corticosteroids were tapered. Thirteen (62%) of 21 patients responded to the
      treatment with MMF, including 6 (60%) of 10 patients with acute refractory GvHD
      and 7 (64%) of 11 patients with chronic refractory GvHD. The most common adverse
      effects were infectious complications (67%, 14 of 21 patients) and hematological
      toxicity (29%, 6 of 21 patients). Median duration of MMF administration was 6
      months (range 1-27 months). Sixteen of 21 patients were alive after the median
      follow-up of 27 months (range 1-72 months) after the initiation of MMF therapy.
      All 16 surviving patients were in good clinical condition and in remission of
      their hematological malignancy. Five patients died--two of relapses of leukemia
      and three of refractory intestinal GvHD. These results suggest that MMF can be an
      effective treatment for some cases of steroid-refractory GvHD.

PMID- 16001245
TI  - [HES 130 as a continuous supplement for organ culture of human corneas?].
AB  - BACKGROUND: During organ culture, corneas swell and have to be de-swollen prior
      to transplantation using a medium. Both swelling and de-swelling lead to
      increased endothelial cell loss. Furthermore, dextran, the standard de-swelling
      substance, is toxic and deposited in the cornea. Whether HES is suitable as a
      continuous supplement for organ culture and keeps the corneas thin was
      investigated in this study. METHODS: Forty-five human corneas were stored in MEM
      plus 7.5% HES 130 for 7, 15, 21, and 28 days. Endothelial cell count was
      determined before and after organ culture. After storage the water content and
      amount of adenosine phosphates were measured. RESULTS: Water content was 82.29%
      after 7 days, 82.98% after 15 days, 81.15% after 21 days, and 83.21% after 28
      days. The endothelial cell count decreased by 1.20% after 7 days, 0.60% after 15
      days, 4.29% after 21 days, and 6.89% after 28 days. ATP was 0.159 micromol/g dry
      weight after 28 days of organ culture. CONCLUSION: The water content of corneas
      stored in HES-containing medium remained constant even after 21 days of organ
      culture. Endothelial cell loss was less than in comparable studies using a
      standard medium containing 10% FCS; however, ATP concentrations were worse. HES
      130 keeps the corneas thin and can be used as a continuous supplement. It
      facilitates the handling of corneas during organ culture, making dehydration
      before transplantation unnecessary, and thus also reduces potential stress
      factors for the cornea.

PMID- 16001246
TI  - Intelligibility of laryngectomees' substitute speech: automatic speech
      recognition and subjective rating.
AB  - Substitute speech after laryngectomy is characterized by restricted aero-acoustic
      properties in comparison with laryngeal speech and has therefore lower
      intelligibility. Until now, an objective means to determine and quantify the
      intelligibility has not existed, although the intelligibility can serve as a
      global outcome parameter of voice restoration after laryngectomy. An automatic
      speech recognition system was applied on recordings of a standard text read by 18
      German male laryngectomees with tracheoesophageal substitute speech. The system
      was trained with normal laryngeal speakers and not adapted to severely disturbed
      voices. Substitute speech was compared to laryngeal speech of a control group.
      Subjective evaluation of intelligibility was performed by a panel of five experts
      and compared to automatic speech evaluation. Substitute speech showed lower
      syllables/s and lower word accuracy than laryngeal speech. Automatic speech
      recognition for substitute speech yielded word accuracy between 10.0 and 50%
      (28.7+/-12.1%) with sufficient discrimination. It complied with experts'
      subjective evaluations of intelligibility. The multi-rater kappa of the experts
      alone did not differ from the multi-rater kappa of experts and the recognizer.
      Automatic speech recognition serves as a good means to objectify and quantify
      global speech outcome of laryngectomees. For clinical use, the speech recognition
      system will be adapted to disturbed voices and can also be applied in other
      languages.

PMID- 16001248
TI  - Mechanical effects of ionic replacements in articular cartilage. Part II:
      Simulations of successive substitutions of NaCl and CaCl(2).
AB  - A three-phase multi-species electro-chemo-mechanical model of articular cartilage
      was developed in a companion paper, Loret and Simoes (in Biomech Model
      Mechanobiol, in press, DOI 10.1007/s10237-004-0062-7). The model can handle
      mechanical and chemical loadings and unloadings involving the two salts, NaCl and
      CaCl(2). In order to reproduce experimental data, the shielding effects are made
      cation-dependent. In a tensile experiment, at constant axial strain, refreshment
      of the bath in contact with the cartilage is observed, and simulated, to induce a
      much different increase in tension depending on the order of the chemical
      sequence to which the cartilage is exposed. For example, the sequence dw
      (distilled water)-NaCl-dw-CaCl(2)-dw results in a decrease in tension. But the
      initial tension is recovered if the chemical sequence is pursued by NaCl-dw.
      Therefore, ionic replacements are essentially reversible, as evidenced when the
      chemical loading events respect a certain symmetry. Distinct shielding effects by
      cations sodium and calcium stem from two main features: (1) different free
      enthalpies of formation that represent different affinities of the proteoglycans
      for these ions and that result in an equilibrium constant not equal to 1; (2)
      distinct valences but approximately the same diameter, which results in a more
      efficient shielding by cations calcium. The model accounts also: (1) for the
      anisotropy of the mechanical properties that are due to the strong orientation of
      collagen fibers; (2) for large deformations that occur during uniaxial traction
      with deionized water.

PMID- 16001247
TI  - The physiological rationale of heat and moisture exchangers in post-laryngectomy
      pulmonary rehabilitation: a review.
AB  - Total laryngectomy results in a permanent disconnection of the upper and lower
      airways and inevitably leads to chronic pulmonary complaints like frequent
      involuntary coughing, increased sputum production and repeated daily forced
      expectoration to clean the airway. Heat and moisture exchangers (HMEs), applied
      in an attempt to compensate for the lost functions of the upper respiratory
      tract, have been found to diminish these symptoms and improve the quality of life
      significantly. An HME has three physical properties that might be responsible for
      these improvements. First, its heat and moisture exchanging capacity improves
      intra-airway preservation of heat and water. Since the condensation and
      evaporation of moisture are accompanied by the release and uptake of thermal
      energy, these parameters are inseparable. Secondly, the HME's resistance may
      reduce dynamic airway compression, thereby improving ventilation. Thirdly, to
      some extent, an HME might filter out particles, thereby cleaning inspiratory
      breathing air. This article summarizes our present knowledge of changes in
      respiratory physiology after total laryngectomy and the influence of the HME by
      reviewing the physiological impact of these three physical properties separately
      for in vitro and in vivo data.

PMID- 16001249
TI  - Mechanical effects of ionic replacements in articular cartilage. Part I: The
      constitutive model.
AB  - A three-phase multi-species electro-chemo-mechanical model of articular cartilage
      is developed that accounts for the effect of two water compartments, namely intra
      fibrillar water stored in between collagen fibrils and extra-fibrillar water
      covering proteoglycans. The collagen fibers constitute the solid phase while
      intra-fibrillar water and dissolved NaCl and CaCl(2) on one hand and extra
      fibrillar water, ions Na(+), Ca(2+) and Cl(-) and proteoglycans on the other
      hand, form the two fluid phases. The complete picture that includes time
      dependent mass transfers between the two fluid phases, diffusion of water and
      ions and electrical flow emerges from the Clausius-Duhem inequality but it is
      deferred to further study. The analysis is restricted to equilibrium states. The
      present work complements the mechanical model developed in Loret and Simoes (Mech
      Material 36(5-6): 515-541, 2004a) where the presence of the sole NaCl was
      considered. In its current version, the model can handle mechanical and chemical
      loadings and unloadings involving the two salts, NaCl and CaCl(2). In order to
      reproduce experimental data, the shielding effects are made cation-dependent.
      Strong orientation of collagen fibers parallel to the joint surface implies
      anisotropic mechanical properties. Electro-chemo-mechanical couplings result in a
      chemistry-dependent apparent tensile Poisson's ratio, that increases to large
      values as the solution gets fresher. The model captures these aspects as well.
      The features of the model are first exposed in an infinitesimal strain context.
      Subsequently, large strains that typically occur in uniaxial traction under
      deionized water are accounted for, and a nonlinear anisotropic hyper-elastic
      behavior is developed. Parametric identification and simulations of actual
      loading processes are described in a companion paper, Loret and Simoes (Biomech
      Model Mechanobiol, in press, DOI 10.1007/s10237-004-0063-6).

PMID- 16001250
TI  - Factors underlying the perturbation resistance of the trunk in the first part of
      a lifting movement.
AB  - In the first part of lifting movements, the trunk movement is surprisingly
      resistant to perturbations. This study examined which factors contribute to this
      perturbation resistance of the trunk during lifting. Three possible mechanisms
      were studied: force-length-velocity characteristics of muscles, the momentum of
      the trunk as well as the effect of passive extending of the elbows. A forward
      dynamics modelling and simulation approach was adopted with two different input
      signals: (1) stimulation of Hill-type muscles versus (2) net joint moments.
      Experimental data collected during an unperturbed lifting movement were used as a
      reference, which a simulated lifting movement had to resemble. Subsequently, the
      simulated lifting movement was perturbed by applying 10 kg extra mass at the
      wrist (both before and after lift-off and with/without a fixed elbow), without
      modifying the input signals. The momentum of the trunk appeared to be
      insufficient to explain the perturbation resistance of trunk movements as found
      experimentally. In addition to the momentum of the trunk, the force-length
      velocity characteristics of the muscles are necessary to account for the observed
      perturbation resistance. Initial extension of the elbow due to the mass
      perturbation delayed the propagation of the load to the shoulder. However, this
      delay is reduced due to the impedance at the elbow provided by the
      characteristics of muscles spanning the elbow. So, the force-length-velocity
      characteristics of the muscles spanning the elbow joint increase the perturbation
      at the trunk.

PMID- 16001251
TI  - L: -Stereoselective amino acid amidase with broad substrate specificity from
      Brevundimonas diminuta: characterization of a new member of the leucine
      aminopeptidase family.
AB  - Brevundimonas diminuta TPU 5720 produces an amidase acting L-stereoselectively on
      phenylalaninamide. The enzyme (LaaA(Bd)) was purified to electrophoretic
      homogeneity by ammonium sulfate fractionation and four steps of column
      chromatography. The final preparation gave a single band on SDS-PAGE with a
      molecular weight of approximately 53,000. The native molecular weight of the
      enzyme was about 288,000 based on gel filtration chromatography, suggesting that
      the enzyme is active as a homohexamer. It had maximal activity at 50 degrees C
      and pH 7.5. LaaA(Bd) lost its activity almost completely on dialysis against
      potassium phosphate buffer (pH 7.0), and the amidase activity was largely
      restored by the addition of Co(2+) ions. The enzyme was, however, inactivated in
      the presence of ethylenediaminetetraacetic acid even in the presence of Co(2+),
      suggesting that LaaA(Bd) is a Co(2+)-dependent enzyme. LaaA(Bd) had hydrolyzing
      activity toward a broad range of L-amino acid amides including L
      phenylalaninamide, L-glutaminamide, L-leucinamide, L-methioninamide, L
      argininamide, and L-2-aminobutyric acid amide. Using information on the N
      terminal amino acid sequence of the enzyme, the gene encoding LaaA(Bd) was cloned
      from the chromosomal DNA of the strain and sequenced. Analysis of 4,446 bp of the
      cloned DNA revealed the presence of seven open-reading frames (ORFs), one of
      which (laaA ( Bd )) encodes the amidase. LaaA(Bd) is composed of 491 amino acid
      residues (calculated molecular weight 51,127), and the deduced amino acid
      sequence exhibits significant similarity to that of ORFs encoding hypothetical
      cytosol aminopeptidases found in the genomes of Caulobacter crescentus,
      Bradyrhizobium japonicum, Rhodopseudomonas palustris, Mesorhizobium loti, and
      Agrobacterium tumefaciens, and leucine aminopeptidases, PepA, from Rickettsia
      prowazekii, Pseudomonas putida ATCC 12633, and Escherichia coli K-12. The laaA (
      Bd ) gene modified in the nucleotide sequence upstream from its start codon was
      overexpressed in an E. coli transformant. The activity of the recombinant
      LaaA(Bd) in cell-free extracts of the E. coli transformant was 25.9 units mg(-1)
      with L-phenylalaninamide as substrate, which was 50 times higher than that of B.
      diminuta TPU 5720.

PMID- 16001252
TI  - Antihyperglycemic effect of polysaccharide from fermented broth of Pleurotus
      citrinopileatus.
AB  - Pleurotus citrinopileatus is an edible mushroom, which has recently become very
      popular, with a consequent increase in industrial production. Water-soluble
      polysaccharides (WSPS), extracted from edible mushrooms, have been found to have
      antitumor and immunoenhancing effects. In this study, we investigate the effects
      of WSPS extracted from submerged fermented medium of P. citrinopileatus on
      hyperglycemia and damaged pancreatic cells in rats with streptozotocin (STZ)
      induced diabetes. The diabetic rats fed with water-soluble polysaccharide of P.
      citrinopileatus (SPPC) lost less body weight than those fed SPPC-free regular
      diet. Serum total cholesterol and triglyceride levels in the diabetic rats fed
      with SPPC at a dose of 0.4 g/kg bw daily was lower than in the groups fed with
      SPPC at doses of 0.04 and 0.12 g/kg bw. The fasting blood glucose levels of
      diabetic rats fed with SPPC were 44% lower than the negative controls. The degree
      of damage to the islets of Langerhans of the rats fed with the highest dosage of
      SPPC was significantly lower than those fed with SPPC at doses of 0.04 and 0.12
      g/kg bw. The results showed that STZ-induced diabetic rats fed with SPPC might
      help alleviate the elevation of the level of that in fasting blood glucose.

PMID- 16001253
TI  - Functional GNA expressed in Escherichia coli with high efficiency and its effect
      on Ceratovacuna lanigera Zehntner.
AB  - The mannose-specific GNA (Galanthus nivalis agglutinin, snowdrop lectin) are the
      resistant proteins with many bioactivities. Snowdrop lectin is different with
      plant organs and development periods in lectin species, content, and
      bioactivities. It is an effective and cheap way to obtain much active GNA through
      overexpression of GNA gene in Escherichia coli. Constructs encoding mature GNA
      fused with an N-terminal pelB signal sequence protein (PelB) were expressed in E.
      coli with high efficiency. Recombinant protein productivity was higher than
      values published before. The insecticidal activity of purified recombinant
      proteins was assayed on feeding sugarcane wooly aphid (Ceratovacuna lanigera
      Zehntner), as well as spraying on sugarcane plants infected by aphids. The
      insecticidal activity was found to be comparable to native GNA. Oral delivery has
      obvious positive implications for crop protection against insect pests since
      peptides can be present in, or sprayed on, plant tissues susceptible to damage. A
      highly efficient expression of functional recombinant GNA would decrease the cost
      of GNA and promote its wide use, especially to give crop protection in the field.

PMID- 16001254
TI  - Antibiotic resistance of bacteria in raw and biologically treated sewage and in
      groundwater below leaking sewers.
AB  - More than 750 isolates of faecal coliforms (>200 strains), enterococci (>200
      strains) and pseudomonads (>340 strains) from three wastewater treatment plants
      (WTPs) and from four groundwater wells in the vicinity of leaking sewers were
      tested for resistance against 14 antibiotics. Most, or at least some, strains of
      the three bacterial groups, isolated from raw or treated sewage of the three
      WTPs, were resistant against penicillin G, ampicillin, vancomycin, erythromycin,
      triple sulfa and trimethoprim/sulfamethoxazole (SXT). Only a few strains of
      pseudomonads or faecal coliforms were resistant against some of the other tested
      antibiotics. The antibiotic resistances of pseudomonads, faecal coliforms and
      enterococci from groundwater varied to a higher extent. In contrast to the faecal
      coliforms and enterococci, most pseudomonads from all groundwater samples,
      including those from non-polluted groundwater, were additionally resistant
      against chloramphenicol and SXT. Pseudomonads from sewage and groundwater had
      more multiple antibiotic resistances than the faecal coliforms or the
      enterococci, and many pseudomonads from groundwater were resistant to more
      antibiotics than those from sewage. The pseudomonads from non-polluted
      groundwater were the most resistant isolates of all. The few surviving faecal
      coliforms in groundwater seemed to gain multiple antibiotic resistances, whereas
      the enterococci lost antibiotic resistances. Pseudomonads, and presumably, other
      autochthonous soil or groundwater bacteria, such as antibiotic-producing
      Actinomyces sp., seem to contribute significantly to the gene pool for
      acquisition of resistances against antibiotics in these environments.

PMID- 16001255
TI  - Microbial xanthophylls.
AB  - Xanthophylls are oxygenated carotenoids abundant in the human food supply.
      Lutein, zeaxanthin, and cryptoxanthin are major xanthophyll carotenoids in human
      plasma. The consumption of these xanthophylls is directly associated with
      reduction in the risk of cancers, cardiovascular disease, age-related macular
      degeneration, and cataract formation. Canthaxanthin and astaxanthin also have
      considerable importance in aquaculture for salmonid and crustacean pigmentation,
      and are of commercial interest for the pharmaceutical and food industries.
      Chemical synthesis is a major source for the heavy demand of xanthophylls in the
      consumer market; however, microbial producers also have potential as commercial
      sources. In this review, we discuss the biosynthesis, commercial utility, and
      major microbial sources of xanthophylls. We also present a critical review of
      current research and technologies involved in promoting microbes as potential
      commercial sources for mass production.

PMID- 16001256
TI  - Optimization and scale up of industrial fermentation processes.
AB  - To increase product yields and to ensure consistent product quality, key issues
      of industrial fermentations, process optimization and scale up are aimed at
      maintaining optimum and homogenous reaction conditions minimizing microbial
      stress exposure and enhancing metabolic accuracy. For each individual product,
      process and facility, suitable strategies have to be elaborated by a
      comprehensive and detailed process characterization, identification of the most
      relevant process parameters influencing product yield and quality and their
      establishment as scale-up parameters to be kept constant as far as possible.
      Physical variables, which can only be restrictedly kept constant as single
      parameters, may be combined with other pertinent parameters to appropriate
      mathematical groups or dimensionless terms. Process characterization is
      preferably based on real-time or near real-time data collected by in situ and on
      line measurements and may be facilitated by supportive approaches and tools like
      neural network based chemometric data analysis and modelling, clarification of
      the mixing and stream conditions through computational fluid dynamics and scale
      down simulations. However, as fermentation facilities usually are not strictly
      designed according to scale-up criteria and the process conditions in the culture
      vessels thus may differ significantly and since any strategy and model can only
      insufficiently consider and reflect the highly complex interdependence and mutual
      interaction of fermentation parameters, successful scale up in most cases is not
      the result of a conclusive and straight-lined experimental strategy, but rather
      will be the outcome of a separate process development and optimization on each
      scale. This article gives an overview on the problems typically coming along with
      fermentation process optimization and scale up, and presents currently applied
      scale-up strategies while considering future technologies, with emphasis on
      Escherichia coli as one of the most commonly fermented organisms.

PMID- 16001257
TI  - Biotransformation of beta-ionone by engineered cytochrome P450 BM-3.
AB  - Wild-type cytochrome P450 monooxygenase from Bacillus megaterium (P450 BM-3) has
      a low hydroxylation activity for beta-ionone (<1 min(-1)). Substitution of
      phenylalanine by valine at position 87 led to a more than 100-fold increase in
      beta-ionone hydroxylation activity (115 min(-1)). Enzyme activity could be
      further increased by both site-directed and random mutagenesis. The mutant R47L
      Y51F F87V, designed by site-directed mutagenesis, and the mutant A74E F87V P386S,
      obtained after two rounds of error-prone polymerase chain reaction, exhibited an
      increase in activity of up to 300-fold compared to the wild-type enzyme. The
      triple mutant R47 LY51F F87V exhibited moderate enantioselectivity, forming (R)-4
      hydroxy-beta-ionone with an optical purity of 39%. All mutants regioselectively
      converted beta-ionone into 4-hydroxy-beta-ionone. The regioselectivity is
      determined amongst others by the absolute configuration of the substrate.

PMID- 16001258
TI  - Engineering Bacillus subtilis ATCC 6633 for improved production of the
      lantibiotic subtilin.
AB  - To improve the production of the lantibiotic subtilin in Bacillus subtilis ATCC
      6633, two genetic engineering strategies were followed. Firstly, additional
      copies of subtilin self-protection (immunity) genes spaIFEG have been integrated
      into the genome of the producer strain. Their expression significantly enhanced
      the subtilin tolerance level, and concomitantly, the subtilin yield 1.7-fold.
      Secondly, a repressor of subtilin gene expression, the B. subtilis general
      transition state regulator protein AbrB, was deleted. A sixfold enhancement of
      the subtilin yield could be achieved with the abrB deletion mutant; however, the
      produced subtilin fraction predominantly consists of succinylated subtilin
      species with less antimicrobial activity compared to unmodified subtilin.

PMID- 16001259
TI  - Gypsy embryo specifies ovule curvature by regulating ovule/integument development
      in rice.
AB  - The embryo position in a seed is stable in most plant species, indicating the
      existence of a strict regulatory mechanism that specifies the embryo position in
      the seed. To elucidate this mechanism, we analyzed the gypsy embryo (gym) mutant
      of rice, in which the position of the mature embryo in the seed is altered at a
      low frequency. Analyses of early embryogenesis and ovule development showed that
      the ectopic embryo was derived from an ill-positioned egg cell, which resulted
      from the incomplete curvature of the ovule. Although the development of both the
      inner and outer integuments was impaired, the ovule curvature was associated
      closely with the extent of inner integument growth. Therefore, inner integument
      development controls ovule curvature in rice. The expression patterns of OSH1 and
      OsMADS13 indicated that, in gym, a small number of indeterminate cells are
      maintained on the style side of the ovule and then in the integument primordium
      at a low frequency. The prolonged survival of these indeterminate cells disturbs
      normal integument development. The gym fon2 double mutant suggests that GYM and
      FON2 are involved redundantly in floral meristem determinacy. Possible functions
      of the GYM gene and the ovule developmental mechanism are discussed.

PMID- 16001260
TI  - Functional characterization of Gossypium hirsutum profilin 1 gene (GhPFN1) in
      tobacco suspension cells. Characterization of in vivo functions of a cotton
      profilin gene.
AB  - Cotton fiber is an extremely long plant cell. Fiber elongation is a complex
      process and the genes that are crucial for elongation are largely unknown. We
      previously cloned a cDNA encoding an isoform of cotton profilin and found that
      the gene (designated GhPFN1) was preferentially expressed in cotton fibers. In
      the present study, we have further analyzed the expression pattern of GhPFN1
      during fiber development and studied its cellular function using tobacco
      suspension cells as an experimental system. We report that expression of GhPFN1
      is tightly associated with fast elongation of cotton fibers whose growth requires
      an intact actin cytoskeleton. Overexpression of GhPFN1 in the transgenic tobacco
      cells was correlated with the formation of elongated cells that contained thicker
      and longer microfilament cables. Quantitative analyses revealed a 2.5-3.6 fold
      increase in total profilin levels and a 1.6-2.6 fold increase in the F-actin
      levels in six independent transgenic lines. In addition to the effect on cell
      elongation, we also observed delayed cell cycle progression and a slightly lower
      mitotic index in the transgenic cells. Based on these data, we propose that
      GhPFN1 may play a critical role in the rapid elongation of cotton fibers by
      promoting actin polymerization.

PMID- 16001261
TI  - Immunohistochemical localization of IAA and ABP1 in strawberry shoot apexes
      during floral induction.
AB  - By using an anti-indole-acetic acid (anti-IAA) monoclonal antibody and an anti
      auxin-binding protein 1 (anti-ABP1) polyclonal antibody, IAA and ABP1 were
      immunohistochemically localized in strawberry (Fragaria ananassa Duch.) shoot
      apexes during floral induction. The spatial distribution patterns of endogenous
      IAA and ABP1 and their dynamic changes during floral induction were investigated.
      In addition, the affect of 1-N-naphthylphtalamic acid (NPA) on IAA distribution
      during floral induction was also analyzed. The results showed that IAA was
      present in the shoot apexes throughout the floral induction process, gradually
      concentrating in the shoot apical meristem (SAM). The distribution of ABP1 and
      its dynamic changes were similar to those of IAA. In addition, the ABP1 immune
      signal in SAM gradually increased as floral induction developed. On a
      morphological level, these results indicate both the spatial distribution and
      dynamic changes in endogenous IAA and ABP1 during the floral induction process.
      The close correlation found between IAA and ABP1 indicates that a cooperation
      occurs during the regulation of floral induction. The results also suggest that
      IAA was the significant agent for floral induction, and that SAM might be the
      place of the main action. Treatment with NPA during floral induction prevented
      the accumulation of IAA in the SAM, delayed the process of floral differentiation
      and induced an abnormal flower development. It is likely that IAA in the shoot
      apex is produced in young leaves and transported through the vascular tissues to
      the SAM and other places of function. Finally, an appropriate amount of IAA in
      the SAM and normal polar auxin transport are essential for floral induction and
      differentiation in strawberries.

PMID- 16001262
TI  - Loss-of-function mutation of the AF9/MLLT3 gene in a girl with neuromotor
      development delay, cerebellar ataxia, and epilepsy.
AB  - The human AF9/MLLT3 gene is a common fusion partner for the MLL gene in
      translocations t(9;11)(p22;q23) associated with acute myeloid leukemia and acute
      lymphocytic leukemia. The exact function of the gene is still unknown, although a
      mouse knock-out model points to a role as a controller of embryo patterning. We
      report the case of a constitutional translocation t(4;9)(q35;p22) disrupting the
      AF9/MLLT3 gene in a girl with neuromotor development delay, cerebellar ataxia and
      epilepsy. Array-CGH analysis at 1 Mbase resolution did not reveal any additional
      deletions/duplications. We hypothesize a loss-of-function mutation of the
      AF9/MLLT3 gene, and a possible role for the FAT gene on chromosome 4, in the
      genesis of the proband's severe neurological phenotype.

PMID- 16001263
TI  - Quantitation of collagen I, collagen II and aggrecan mRNA and expression of the
      corresponding proteins in human nucleus pulposus cells in monolayer cultures.
AB  - Cells that are taken from the nucleus pulposus (NP) and that are allowed to
      proliferate in monolayer cultures often exhibit changes in their cell morphology
      and matrix-protein synthesis. However, whether concomitant alterations occur with
      respect to their mRNA levels for collagen I (CI), collagen II (CII) and aggrecan
      (AGG) is unclear. In this study, human NP cells from seven individuals were
      cultured in monolayers and specific mRNAs for CI, CII and AGG were quantified by
      real-time polymerase chain reaction in fresh NP tissue and during four passages
      of NP-cell culture. In addition, the presence of CI, CII and AGG protein was
      determined by immunofluorescence staining of NP cells. We found a significant
      reduction of CI, CII and AGG mRNA after the initiation of culture in DMEM
      compared with mRNA levels in fresh NP tissue. During passages 2--4, no further
      reduction of mRNA levels for CII and AGG was observed. The mRNA level for CI was
      reduced significantly with duration of culture. Immunofluorescence staining of
      cultured NP cells revealed expression of CI, CII and AGG protein during the whole
      culture period. Our data thus demonstrate a reduction of specific mRNA for matrix
      proteins during the initiation of NP-cell culture but the stable expression of
      the key matrix proteins, CII and AGG, during further expansion of the cells in
      monolayers, suggesting no functional changes occur in cultured NP cells.

PMID- 16001264
TI  - Reissner's fiber formation depends on developmentally regulated factors extrinsic
      to the subcommissural organ.
AB  - Reissner's fiber (RF) is a threadlike structure present in the third and fourth
      ventricles and in the central canal of the spinal cord. RF develops by the
      assembly of glycoproteins released into the cerebrospinal fluid (CSF) by the
      subcommissural organ (SCO). SCO cells differentiate early during embryonic
      development. In chick embryos, the release into the CSF starts at embryonic day 7
      (E7). However, RF does not form until E11, suggesting that a factor other than
      release is required for RF formation. The aim of the present investigation was to
      establish whether the factor(s) triggering RF formation is (are) intrinsic or
      extrinsic to the SCO itself. For this purpose, SCO explants from E13 chick
      embryos (a stage at which RF has formed) were grafted at two different
      developmental stages. After grafting, host embryos were allowed to survive for 6
      7 days, reaching E 9 (group 1) and E13 (group 2). In experimental group 1, the
      secretion released by the grafted SCOs never formed a RF; instead, it aggregated
      as a flocculent material. In experimental group 2, grafted SCO explants were able
      to develop an RF-like structure, similar to a control RF. These results suggest
      that the factor triggering RF formation is not present in the SCO itself, since
      E13 SCO secretion forms an RF in E13 brains but never develops RF-like structures
      when placed in earlier developmental environments. Furthermore, the glycoproteins
      released by implanted SCOs bind specifically to several structures: the apical
      portion of the mesencephalic floor plate and the choroid plexus of the third and
      fourth ventricles.

PMID- 16001265
TI  - Multiunit arrector pili muscular structure as a variation observed by using
      computer-based three-dimensional reconstruction.
AB  - The arrector pili (AP) muscle was recently suggested to comprise one AP muscular
      unit inserted into all the hair follicles contained within the follicular unit
      (FU). This study investigated the presence of variations in AP muscular units
      associated with the FUs. Human cadaver scalp skin specimens were serially
      sectioned and stained with Masson's trichrome. Three-dimensional reconstructions
      of the serially sectioned images were analyzed on a computer, which revealed two
      types of variation in 20 FUs, one of which was the multiunit AP muscular
      structure, in which the AP muscular unit was inserted into two or more FUs.

PMID- 16001266
TI  - Localization of interleukin-18 and its receptor in somatotrophs of the bovine
      anterior pituitary gland.
AB  - A pro-inflammatory cytokine, interleukin 18 (IL-18), induces intracellular
      expression of IL-1 and the release of IL-6. IL-1 and IL-6 has been detected in
      anterior pituitary cells, suggesting that IL-18 is produced in anterior pituitary
      cells and may serve to aid immuno-endocrine regulation. In the present study, we
      addressed this hypothesis by investigating the intracellular localization of IL
      18 and its receptor in bovine anterior pituitary gland. IL-18 mRNA and its
      protein were detected in the anterior pituitary gland by RT-PCR and Western
      blotting. In situ hybridization showed that IL-18 mRNA was expressed in the
      anterior pituitary cells. Immunohistochemistry of IL-18 and specific hormones
      revealed the presence of IL-18 in somatotrophs. Furthermore, the expression of GH
      mRNA in IL-18 immunoreactive cells was confirmed by immuno-laser microdissection.
      These results first demonstrated that somatotrophs produced IL-18. Subsequently,
      the distribution of the IL-18 receptor alpha (IL-18Ralpha) was investigated in
      order to understand IL-18 signaling among the anterior pituitary cells. Bovine IL
      18Ralpha cDNA was partially sequenced and detected in the anterior pituitary
      gland by RT-PCR. Immunohistochemistry of IL-18Ralpha, IL-18 and GH showed that IL
      18Ralpha was co-localized in IL-18 immunoreactive cells or somatotrophs. These
      data suggest that IL-18 acts on somatotrophs as an immuno-endocrine mediator
      through the autocrine pathway.

PMID- 16001267
TI  - Corticotropin-releasing factor (CRF) expression in postnatal and adult rat sacral
      parasympathetic nucleus (SPN).
AB  - The neural control of micturition undergoes marked changes during the early
      postnatal development. During the first few postnatal weeks, the spinal
      micturition reflex is gradually replaced by a spinobulbospinal reflex pathway
      that is responsible for micturition in adult animals. Upregulation of brainstem
      regulation of spinal micturition pathways may contribute to development of mature
      voiding patterns. We examined the expression of corticotropin-releasing factor
      (CRF), present in descending projections from Barrington's nucleus to the sacral
      parasympathetic nucleus (SPN), in postnatal (P0-P36) and adult Wistar rats (P60
      90). CRF-immunoreactivity (IR) was present predominantly in the SPN region,
      although some staining was also observed in the dorsal horn and dorsal commissure
      in L5-S1 spinal segments. CRF-IR in spinal cord regions was age dependent
      (R2=0.87-0.98). The majority of the CRF-IR in the lumbosacral spinal cord was
      eliminated by complete spinalization (2-3 weeks). Double-label
      immunohistochemistry was combined with quantitative confocal laser scanning
      microscopy to quantify the number and percentage of colocalization between CRF
      immunoreactive varicosities and preganglionic somas or proximal neurites in the
      SPN in postnatal and adult rats. Results demonstrate an age-dependent
      upregulation of CRF-IR in the SPN region and specifically in association with
      preganglionic parasympathetic neurons identified with neuronal nitric oxide
      synthase (nNOS)-IR. CRF-immunoreactive varicosities on or within a 1 microm
      perimeter of nNOS-immunoreactive somas or proximal neurites also increased with
      postnatal age. The upregulation of CRF-IR in bulbospinal projections to the SPN
      may contribute to mature voiding reflexes.

PMID- 16001268
TI  - In vitro cartilage formation of composites of synovium-derived mesenchymal stem
      cells with collagen gel.
AB  - Graft implantation is one of the more popular procedures for repairing cartilage
      defects; however, sacrifices of the donor site have been an issue. Mesenchymal
      stem cells (MSCs) are a fascinating source for regenerative medicine because they
      can be harvested in a less invasive manner and are easily isolated and expanded,
      with multi-potentiality including chondrogenesis. MSCs can be isolated from
      various adult mesenchymal tissues including synovium. Here, we attempted to form
      cartilage from the composites of synovium-derived MSCs with collagen gel in
      vitro. After 21 days of culture, the composites had increased their cartilage
      matrix, as demonstrated by toluidine blue staining and immunohistochemistry for
      type II collagen. The composites consisting of 5 x 10(7) and 10(8) cells/ml in
      gel were richer in proteoglycans than those consisting of lower cell densities.
      After 1 day, MSCs/gel composites contracted and the diameter decreased by 30%;
      however, they were stable thereafter. Round cells with short processes producing
      collagen fibrils showing a similar morphology to that of chondrocytes were seen
      in the composites by transmission electron microscopy. During composite culture,
      chondroitin sulfate and mRNA expression for cartilage-related genes increased,
      demonstrating cartilage maturation. Using an optimized method, we obtained
      cartilage discs with a diameter of 7 mm and a thickness of 500 microm. Our
      procedure should thus make it possible to produce a large cartilage matrix in
      vitro. The tissue engineering of autologous cartilage from the composites of
      synovium-derived MSCs with collagen gel in vitro for transplantation may be a
      future alternative to graft implantation for patients with cartilage defects.

PMID- 16001269
TI  - [Bibliometric analysis of anaesthetic molecular biology research in Germany,
      Austria and Switzerland].
AB  - BACKGROUND: In the last 20 years molecular biology has expanded the horizons of
      medical research including anaesthesia. Preoperative identification of genetic
      disorders relevant to anaesthesia or increased perioperative risk will be
      available in the near future using molecular biology techniques. There has been a
      global increase of such publications, but the contributions from Germany,
      Switzerland and Austria are unknown. MATERIAL AND METHODS: An internet-based
      medline search was used to analyse specific features such as year of publication,
      journal and origin of molecular biology articles produced by German, Swiss and
      Austrian anaesthesia institutions from 1988 to 2002. RESULTS: During the study
      period 121 articles from German institutions were published, 18 from Switzerland
      and 5 from Austria, corresponding to 10%, 1.5% and 0.4%, respectively, of global
      publications. In Germany the number of anaesthesia publications with a molecular
      biology content has continuously increased, but in Switzerland and Austria the
      numbers have remained constant. The majority of articles were published in high
      impact non-anaesthesia journals. DISCUSSION AND CONCLUSION: The results of this
      study show the quantitative development of molecular biology research that has
      been done in anaesthesia institutions in Germany, Switzerland and Austria from
      1988 to 2002. A continuous increase of publications with a molecular biology
      content occurred only in Germany.

PMID- 16001270
TI  - [Current developments in DICOM and IHE].
AB  - The broadening use of imaging management systems in radiology and other
      disciplines is due in large part to the success of the DICOM standard (Digital
      Imaging and Communications in Medicine), which has been accepted worldwide for
      more than 10 years and meanwhile represents one of the most successful standards
      in medicine. The central intent of establishing the initiative "Integrating the
      Healthcare Enterprise" (IHE) was to ensure interoperability of different IT
      systems in medical processes. IHE is essentially based on widespread standards
      such as DICOM or HL7. This overview article briefly addresses the principles and
      organization of DICOM and IHE and describes the current developments in both
      domains.

PMID- 16001271
TI  - Involvement of tumor necrosis factor-alpha in sulfur mustard-induced skin lesion;
      effect of topical iodine.
AB  - Sulfur mustard (SM), also termed mustard gas, is a potent vesicant that elicits
      an inflammatory response upon exposure of the skin. Evaluation of mouse ear 3 h
      after SM exposure revealed acute inflammatory-cell aggregates in the vascular
      beds accompanied by strongly TNF-alpha-positive neutrophils. Eight hours after SM
      exposure, this phenomenon became intensified and associated with infiltration
      into the adjacent dermis. In ear skin topically treated with iodine, however, no
      inflammatory cells were observed 3 h after SM exposure; 8 h postexposure, blood
      vessels contained very few TNF-alpha-positive inflammatory cells. Since TNF-alpha
      induction was shown to be associated with reactive oxygen species production, we
      studied the effect of iodine on activated peritoneal mouse neutrophils. Iodine
      elicited a concentration-dependent reduction in the oxidative burst of activated
      neutrophils. Iodine also scavenged hydroxyl radicals generated by glucose oxidase
      in a concentration-dependent manner. The involvement of TNF-alpha in SM-induced
      skin toxicity was confirmed by reduction of 49 and 30% in ear edema following
      administration of 1 and 2 mug anti-TNF-alpha antibodies, respectively. These
      findings were corroborated by quantitative analysis of the histological findings
      showing 46% reduction in acute inflammation and no signs of subacute inflammation
      in the treated group, in contrast to the control group treated with SM only.
      Other epidermal (microblister formation, ulceration, and necrosis) and dermal
      (neutrophilia, hemorrhage, and necrosis) parameters also showed marked reductions
      in the antibodies-treated group in comparison to controls. The combination of
      iodine and antiTNF-alpha antibodies might constitute a new approach for treatment
      of SM-exposed individuals.

PMID- 16001272
TI  - Bilateral ocular osseous choristomas.
AB  - Choristoma is a benign tumour defined as normal tissue in an ectopic location.
      Osseous choristoma, one subtype of this entity, occurring within the orbit has
      rarely been reported in the world literature. We report a 6-year-old girl with
      bilateral ocular osseous choristomas who presented with palpable nodules
      protruding from both upper lids. The radiological and clinical findings are
      described and previous reports are reviewed.

PMID- 16001273
TI  - Evaluation of the apoptosis-related proteins of the BCL-2 family in the traumatic
      penumbra area of the rat model of cerebral contusion, treated by hyperbaric
      oxygen therapy: a quantitative immunohistochemical study.
AB  - The growth and progression of traumatic brain injury (TBI) lesions depend
      significantly on developments in the traumatic penumbra area, perilesional
      region, where delayed neuronal death occurs. Recent data supports the important
      role of apoptosis in delayed cell death in TBI. Previously we demonstrated a
      significant reduction of apoptosis in traumatic penumbra in animals treated by
      hyperbaric oxygen (HBO). In this study we evaluate the expression of apoptosis
      related proteins of the Bcl-2 family (Bcl-2, Bax and Bcl-xL) in the traumatic
      penumbra area in correlation with the extent of apoptosis in the rat model of
      focal cerebral contusion, treated by HBO. Sprague-Dawley rats underwent cortical
      dynamic deformation, some with subsequent hypoxemia. A group of both hypoxemic
      and non-hypoxemic animals was treated by HBO. The pathological study was based on
      immunohistochemical staining of the brain sections for Bcl-2, Bax and Bcl-xL with
      quantitative evaluation of staining by image analysis. The expression of Bcl-2 in
      hypoxemic animals was lower than in non-hypoxemic animals, but a significant
      increase in Bcl-2 expression was seen in both groups after HBO treatment. Bcl-xL
      also demonstrated an increase after HBO treatment but less significant. Staining
      for Bax protein did not demonstrate significant change after treatment. These
      data correlate well with the reduction of TUNEL-positive cells in traumatic
      penumbra after HBO treatment. We concluded that the apoptotic mechanisms are
      important in delayed cell death in TBI and that post-traumatic hypoxemia
      increases the intensity of apoptosis, probably through a decrease in Bcl-2 and
      Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO
      treatment in our model of brain contusion correlates well with the increased
      expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and
      the appropriate decrease in the extent of apoptosis. In light of these results,
      the usage of HBO is justified as neuroprotective treatment in TBI.

PMID- 16001274
TI  - Contractile physiology and response to temperature changes of the tunica dartos
      muscle of the rat.
AB  - We show here that explants of tunica dartos smooth muscle from the rat scrotum
      contract in response to cooling. The tension developed during cooling was
      potentiated by the presence of the overlying skin. This potentiation remained
      even if direct connection between the muscle and skin was severed by cutting the
      skin from the muscle but leaving the muscle and skin in contact. The potentiation
      did not depend on any inherent response of the skin since isolated skin showed no
      change in tension with cooling. The muscle exhibited a sigmoid dose response to
      noradrenaline with an EC(50) (dose for 50% contractile response) of 1.03+/-0.02 x
      10(-6) M. Acetylcholine altered neither resting tone or the sustained contraction
      induced by a submaximal dose of noradrenaline. The contractile response to an
      EC(50) and maximal dose of noradrenaline was attenuated at both 15 and 40 degrees
      C relative to the response observed at 33 degrees C. We hypothesise that the
      potentiation of tunica dartos muscle contraction with cooling caused by the
      presence of the scrotal skin depends on some soluble agent released from the skin
      and affecting the underlying muscle. Noradrenaline release from the skin, or some
      molecule with alpha-receptor activity, may account for a small proportion of the
      potentiation. The remainder of the effect does not depend on prostaglandins, or
      other products of the cyclooxygenase cascade, or the nitric oxide system.

PMID- 16001275
TI  - Action of ANG II and ANP on colon epithelial cells.
AB  - The interaction of angiotensin II (ANG II) and atrial natriuretic peptide (ANP)
      on intracellular pH (pH(i)) and calcium ([Ca2+](i)) was investigated in T84 cells
      (a permanent cell line derived from human colon epithelium) using the fluorescent
      stains BCECF/AM and Fluo 4/AM, respectively. pH(i) recovery rate mediated by the
      Na(+)/H+ exchanger (NHE) was examined following an NH4Cl pulse. Under control
      conditions pH(i) recovered at 0.114+/-0.005 pH units/min (n=35). ANG II (10(-12)
      or 10(-9) M) increased this value, whilst ANG II (10(-7) M) decreased it. These
      effects of ANG II were impaired by simultaneous addition of 1 microM or 25 microM
      HOE-694, indicating that the stimulatory and inhibitory effects of ANG II on
      pH(i) recovery are mediated in part via the NHE1 and NHE2 isoforms. ANG II
      increased [Ca2+]i concentration-dependently. ANP (10(-6) M) or dimethyl-BAPTA/AM
      (50 microM) blocked the effects of ANG II on [Ca2+]i and on the rate of pH(i)
      recovery. Thapsigargin (10(-5) M) enhanced the effect of ANG II on [Ca2+]i and
      reversed its stimulatory effect on the rate of pH(i) recovery to an inhibitory
      one. External Ca(2+)-free solution did not affect the effects of ANG II on these
      parameters. These data suggest that the [Ca2+]i increase induced by ANG II is
      dependent on intracellular calcium stores. They are compatible with the
      demonstration of two sites on the C-terminal of the Na(+)/H+ exchanger, one
      stimulating Na(+)/H+ activity by increases of [Ca2+]i in the lower range (at 10(
      12) or 10(-9) M ANG II) and the other inhibiting this activity at high [Ca2+]i
      levels (at 10(-7) M ANG II). ANP or dimethyl-BAPTA/AM, by impairing the pathway
      mediating the increase in [Ca2+]i, block both the stimulatory and inhibitory
      effects of ANG II.

PMID- 16001277
TI  - Duration estimation and the phonological loop: articulatory suppression and
      irrelevant sounds.
AB  - Clock-based theories of time estimation propose that clock pulses are accumulated
      in working memory. Although these theories do not constrain the form of the
      memory trace, evidence reported in the literature suggests that active
      manipulation of a verbal trace may be involved. Four experiments are reported in
      which participants reproduced or verbally estimated short durations (up to a few
      seconds) either in a single-task condition or in a condition with a phonological
      load. Experiments 1, 2 and 4 showed that both interval reproduction and verbal
      estimation were impaired under concurrent articulatory suppression in comparison
      to a timing only control condition. Neither irrelevant speech (Experiments 1-3)
      nor irrelevant tones and music (Experiment 3) impaired timing performance. These
      findings are taken to show that time estimation is mediated by phonological
      working memory and the involvement of an active articulatory rehearsal process.

PMID- 16001276
TI  - TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors.
AB  - Within the transient receptor potential (Trp) superfamily of ion channels, three
      members of the Trp (melastatin) (TRPM) subfamily stand out as their amino acid
      sequences indicate that they possess both ion channel and enzymatic functions.
      Recently, progress has been made in understanding the relationships between these
      disparate functionalities for two of these proteins, TRPM2 and TRPM7. TRPM2
      appears to have adapted an ADP-ribose hydrolase (ADPRibase) enzyme's structure as
      a means of binding ADP-ribose and conveying information about the accumulation of
      ADP-ribose to the cell via the activation of Na(+)/Ca(2+) entry through the
      channel domain. While the ADPRibase activity of TRPM2's enzymatic domain is not
      required for channel gating, whether a converse relationship exists, wherein
      channel gating or ion flow modulates the enzymatic domain's ADPRibase activity,
      is not known. In contrast, TRPM7 appears to have evolved to place a Mg(2+)
      regulated protein kinase domain in close proximity to a Mg(2+)-permeant ion
      channel, such that the kinase domain's phosphotransferase activity is able
      respond to local changes in free Mg(2+) occurring as the result of the flux of
      Mg(2+) through the channel. As with TRPM2, the activity of TRPM7's enzymatic
      domain is not required for gating of its channel domain, although evidence exists
      that it may have an alternative means of influencing channel gating. These
      insights into the functional relationships between the channel and enzymatic
      domains of TRPM2 and TRPM7 suggest informative models for their roles in
      vertebrate cell physiology.

PMID- 16001278
TI  - Mental contents in transfer.
AB  - The purpose of this paper is to develop theoretical concepts for mental content
      based investigations and explanations in the psychology of human thinking in
      general and transfer more specifically. The schema-based analysis of transfer
      postulates that the solving of an earlier problem can influence a person's future
      behavior only to the degree of schematic similarity between the primary and the
      secondary problem solution. The reported content-based investigation, using
      Duncker's (1935) classic tumor task, shows however, that the contents of schemata
      cause an essential variation in a person's mental representation and judgement of
      radiation confluence effects. The study identified and assessed in separate
      experiments the influence of three different thought models (additive, balancing,
      and distribution-based) and two distinct types of spatial images of rays (compact
      vs. diverging). Whereas differences in the central tendencies of the judgements
      could expose some of the priming effects between experimental conditions, the
      core of the content-based analysis was based on the identification of distinct
      groups of participants displaying a certain type of judgement. These differences
      reflected the contrasts between the thought models and the ray image content.
      They substantiated the claim that a schema-based analysis of transfer and
      reasoning in general, is alone not sufficient to explain interindividual and
      intercontextual differences that are based on distinctive mental content in the
      reasoners' apperception.

PMID- 16001279
TI  - Diarrhea, CD4+ cell counts and opportunistic protozoa in Indian HIV-infected
      patients.
AB  - The aim of this study was to examine the relationships among diarrhea, CD4+ cell
      counts and opportunistic protozoa in HIV-infected patients in North India. In a
      retrospective study, blood and stool samples of 200 HIV-infected patients from
      March 2001 until 2003, submitted to the AIDS division of National Institute of
      Communicable Diseases (NICD), were analyzed. Each patient was examined for
      opportunistic protozoa, HIV-1 status and CD4+ cell counts, and screened for
      diarrheal symptoms. The rate of diarrhea was 38% in the stool examination. In HIV
      infected patients in the groups CD4+ > 500 cells/microL, 200 cells/microL < CD4+
      < 500 cells/muL and in the AIDS patients CD4+ < 200 cells/microL, diarrhea was
      14.7, 29.8 and 56.1%, respectively. It is clear that the diarrhea in the AIDS
      patients was significant compared with the two former groups (P < 0.0005). In the
      AIDS patients CD4+ < 200 cells/microL with diarrhea, Cryptosporidium infection
      was, at 56.5%, the highest and statistically significant compared with the other
      parasites (P = 0.037). Microsporidium was detected in 30.4% of the AIDS patients.
      Diarrhea was common and most strongly associated in patients with low CD4+ cell
      counts. The data stress the importance of opportunistic protozoa in the HIV
      infected patients, and that opportunistic protozoa should be expected in HIV
      infected patients with low CD4+ and diarrhea.

PMID- 16001280
TI  - Strains of Toxoplasma gondii used for tachyzoite antigens to stimulate spleen
      cells of infected mice in vitro affect cytokine responses of the cells in the
      culture.
AB  - Cytokine responses of lymphocytes against Toxoplasma gondii are usually studied
      by stimulating the cells from infected animals with tachyzoite lysate antigens
      (TLA) in vitro. We examined whether strains (genotypes) of the parasite used for
      TLA affect the production of IL-2, IL-4, IL-10 and IFN-gamma in the culture of
      spleen cells obtained from mice infected with the ME49 (type II) strain. The
      amounts of IL-2 and IL-4 detected in the culture supernatants following
      stimulation with TLA of the RH (type I) strain were significantly greater than
      those detected following stimulation with TLA of the ME49 strain at 2 and 4 weeks
      after infection, respectively. These results suggest that antigen variations
      among the strains of T. gondii affect cytokine production of lymphocytes of
      infected mice. Therefore, to obtain accurate information on cytokine production
      by immune lymphocytes of infected hosts, it is important to use the identical
      strain of T. gondii for both infection of animals and preparation of TLA to
      stimulate the lymphocytes in vitro.

PMID- 16001281
TI  - Oxidative stress in children with kidney disease.
AB  - The aim of this work was to study the dynamics of oxidative stress in the blood
      and urine of children with kidney diseases: glomerulonephritis (GN),
      pyelonephritis (PN), renal failure (RF), and lower urinary tract infections
      (LUTI). The concentration of conjugated dienes is increased in blood: GN 4 times
      and RF up to 2 times; and extremely increased in urine: GN 12 times and RF 4
      times. The concentration of thiobarbituric acid reactive substances in urine
      shows a similar trend: GN 7 times, PN 2 times, RF 1.5 times, and LUTI almost 3
      times. Urine chemiluminescence is also increased: GN 5 times, PN and LUTI 3
      times, and RF 6 times. Kidney disease leads to 2.5-fold inhibition of antioxidant
      catalase activity in blood and 10-fold in urine. Total antioxidant activity of
      urine is induced in all groups: GN 18 times, PN 2 times, RF 1.5 times, and almost
      4 times in the LUTI group. Experimental data confirm that products of lipid
      peroxidation, intensity of chemiluminescence, and total and enzyme antioxidant
      capacity in combination with clinical parameters are a proper test for the
      dynamics of oxidative stress and markers of intoxication in children with
      inflammatory and immunological active parenchymal kidney disorders. These data
      could be helpful for the optimization of complex and effective antioxidant
      therapy of children with kidney disease.

PMID- 16001282
TI  - [Causal illness attributions and healthcare utilization in fibromyalgia
      syndrome].
AB  - INTRODUCTION: High utilization of medical services has been described for
      patients with fibromyalgia syndrome (FMS). There are no studies available that
      assess whether the patients' subjective illness beliefs influence their behavior
      in utilizing healthcare. METHODS: Examinations were performed by taking the
      history of pain treatment in 100 FMS patients evaluated by experts for the social
      court and 25 patients attending an outpatient pain center. The subjective illness
      theories were drawn from the patients' responses to the German Pain Questionnaire
      (GPQ). The statements made on the GPQ regarding utilization of healthcare
      services were compared with the records and the answers given in the interview on
      pain therapy. RESULTS: Of the patients, 44% specified a somatic, 2% a
      psychogenic, 9% none, and 45% a psychosomatic illness belief. The patients were
      classified as high utilizers of specialized medical services in 25% of the cases
      and of psychiatric-psychotherapeutic services in 14%. No significant correlations
      between the type of subjective illness theory and utilization of specialized
      medical or psychiatric-psychotherapeutic services were observed. CONCLUSION: From
      the psychosomatic viewpoint, only part of the FMS patients exhibited an
      inordinately one-sided somatic illness belief. The utilization of healthcare
      services cannot be explained by the subjective perception of the illness.

PMID- 16001283
TI  - Neoplastic fever: all who shiver are not infected.

PMID- 16001284
TI  - Age and gender related effects on adipose tissue compartments of subjects with
      increased risk for type 2 diabetes: a whole body MRI/MRS study.
AB  - Quantitative measurement of adipose tissue (AT) compartments in the entire body
      and of lipids in muscle and liver cells by means of MRI and MRS. Assessment of
      age and gender related differences in AT compartments and determination of cross
      correlations between AT compartments in a heterogeneous cohort at increased risk
      for metabolic diseases. One hundred and fifty healthy volunteers with increased
      risk to type 2 diabetes were examined. T1-weighted MRI was applied for whole-body
      adipose tissue quantification. Adipose tissue compartments were subdivided in
      lower extremities, trunk (abdominal subcutaneous (SCAT) and visceral (VAT)
      adipose tissue), and upper extremities. Intrahepatocellular lipids (IHCL) and
      intramyocellular lipids (IMCL) in tibialis anterior and soleus muscle were
      determined by volume selective MRS. Females are characterized by lower %VAT
      (2.8+/-1.3% vs. 4.6+/-1.4%, p<0.001) and higher %SCAT (14.7+/-3.9% vs. 9.3+/
      2.9%, p<0.001). There is a strong correlation between %VAT and age (r=0.64/0.60
      for females/males), whereas %SCAT remained virtually unchanged in males (r=-0.09)
      and was only slightly increaseding in females (r =0.30, p<0.01). For IHCL, age
      related differences were observed in females with significantly increased IHCL in
      the older women, but not in males. IMCL contents in both muscles were found
      almost independent of age in both, males and females. Furthermore, VAT and IHCL
      show significant correlations in both groups. Assessed age and gender related
      differences, especially the age related significant increase of VAT and IHCL, as
      well as cross-correlations between different lipid compartments might contribute
      to a better understanding of the lipid metabolism under normal and pathologic
      metabolic conditions in humans.

PMID- 16001285
TI  - TNM classification for perihilar cholangiocarcinoma: comparison between 5th and
      6th editions of the AJCC/UICC staging system.
AB  - BACKGROUND: A few investigators have evaluated the TNM classification for
      perihilar cholangiocarcinoma. The new sixth edition of the American Joint
      Committee on Cancer (AJCC)/Internal Union Against Cancer (UICC) staging system
      focuses on vascular invasion and regional lymph node metastasis. METHODS: For 166
      patients with perihilar cholangiocarcinoma undergoing R0 resection, survival
      curves stratified according to TNM classifications were compared between fifth
      and sixth editions. RESULTS: The previous T3 now is divided into T3 and T4. Most
      new pT4 patients had invasion of the portal bifurcation; their survival was
      poorer than that for new pT3 patients. The 5-, 10-, and 15-year survival rates
      were worse in the previous stage III than in the previous stage IVA, although the
      difference fell short of significance. The previous stage IVA (T3 Any NM0) is
      divided into new stages: IIA (T3N0M0), IIB (T1-3N1M0), and III (T4 Any NM0). All
      patients in stage III had invasion of the portal bifurcation. Survival was
      similar between stages IA, IB, and IIA, while patients with T4N0M0 tumors
      survived longer than those with T4N1M0 tumors and similarly to those with stage
      IIB tumors. CONCLUSIONS: The sixth edition provided improved prediction of
      survival in patients with perihilar cholangiocarcinoma; for still better
      prediction, cancer invasion of the portal bifurcation and regional lymph node
      metastasis should be weighted equally.

PMID- 16001287
TI  - Hemifacial spasm caused by pontine glioma: case report and review of the
      literature.
AB  - Hemifacial spasm (HFS) is an involuntary paroxysmal contractions of the facial
      musculature, caused generally by vascular compression of the seventh cranial
      nerve at its root exit zone from the brain stem. The case of an adult man
      harbouring brain stem glioma (BSG) whose only neurological signs were left HFS
      and mild facial weakness is reported. Radiological and neurophysiological
      findings are described. No responsible vessel could be identified during surgery,
      but the causative lesion was found to be an astrocytic tumour encasing the facial
      nerve at its root exit zone from the brain stem. The rarity of such a condition
      prompted us to review the literature. Nine cases, including our patient
      presenting with HFS caused by BSG, are reviewed.

PMID- 16001286
TI  - Craniopharyngiomas in children: Turkey experience.
AB  - OBJECTIVES: Craniopharyngiomas are the most frequently encountered suprasellar
      tumors in children. Although they have a benign histology, total resection
      without morbidity is very difficult. METHODS: We aimed to review the results of
      pediatric craniopharyngioma patients treated in eight institutions in Turkey.
      There were 51 boys and 36 girls, ranging in age from 20 months to 18 years (mean
      10.2 years). The most frequent symptom was headache, followed by visual
      disturbances. Hydrocephalus was seen most frequently in tumors greater than 4 cm
      in size (P=0.002). Hydrocephalus was associated with the decreased gross total
      resection (P=0.043). The recurrence (28%) was significantly higher in patients
      with subtotal and partial tumor removal (P=0.010). Bad outcome was significantly
      associated with tumor dimension (P=0.039); the greater the tumor dimension, the
      worse the outcome. Outcome was significantly better in patients older than 10
      years (P=0.032). Gender, tumor type and location, presence of hydrocephalus and
      calcification, histological type of craniopharyngioma, and surgical approach did
      not have a significant effect on the outcome. CONCLUSIONS: The treatment should
      be individualized and a multidisciplinary approach should be used. The goal of
      surgery should be gross total removal without mortality and with acceptable
      morbidity.

PMID- 16001288
TI  - Biomechanical comparison of posterior cruciate ligament reconstruction techniques
      using cyclic loading tests.
AB  - Posterior tibial translation (PTT) of the posterior cruciate ligament (PCL)
      reconstructed-knee under cyclic loading of 1,000 cycles with a 100-N load was
      compared between four different procedures, including two reconstructions with
      patellar tendon graft (transtunnel and inlay techniques) and two reconstructions
      with hamstring tendon graft (Endobutton and EndoPearl techniques) in twelve fresh
      frozen human knees. The EndoPearl technique is a direct tendon fixation using
      biodegradable interference screws and an anchoring device, while the Endobutton
      technique is an indirect tendon fixation using a titanium button and surgical
      tape. The change of PTT after cyclic loading in the Endobutton technique was
      significantly greater than in the other reconstruction technique. No graft
      rupture at the killer turn or complete pullout from the bone tunnel was found.
      The advantage of the inlay technique compared to the transtunnel technique with
      respect to the posterior stability could not be shown in the current study.
      Posterior laxity of PCL reconstructed-knees with hamstring tendon graft using the
      Endobutton technique increased more easily than that with patellar tendon graft.
      For PCL reconstruction using the hamstring tendon graft, anatomical fixation may
      be preferable to prevent excessive posterior laxity in the early phase of the
      rehabilitation protocol.

PMID- 16001289
TI  - Cadaveric study on static medial patellar stabilizers: the dynamizing role of the
      vastus medialis obliquus on medial patellofemoral ligament.
AB  - Aim of this cadaveric biomechanical study was to describe the detailed anatomy of
      the static medial patellar stabilizers and further determine the role of each of
      them in preventing lateral patellar dislocation. Eight cadaver knees, after
      removing the skin and subcutaneous tissues, were used in the study. The medial
      patellofemoral ligament (MPFL), the medial retinaculum (MR) the medial
      patellomeniscal ligament (MPML), and the medial patellotibial ligament (MPTL)
      were dissected. Their origins, insertions, orientations and sizes were recorded.
      To the medial stabilizers, a tension of 10 pounds was applied, using a
      tensiometer held in a semicircular device while the knees were kept in 30 degrees
      of flexion. Then, the previously described ligaments were dissected and the
      resultant displacement recorded. The most anatomically distinct structure is the
      MPFL, whose length varies from 45-50 mm, and its width from 10-20 mm at its
      origin (medial femoral epicondyle) to 20-30 mm at its insertion to the patella.
      The "meshing" of the MPFL fibers to the fibers of the vastus medialis obliquus
      (VMO) close to its patellar insertion was the most interesting and very important
      finding. The contribution of MPFL to medial stability was more than 50%. Of the
      remaining ligaments, MPML contributes 24% and the MPTL and MR contribute only 13%
      respectively. The MPFL is the strongest medial static patellar stabilizer. Its
      contribution to patellar stability against lateral dislocation is far more than
      50%, since its meshing with the VMO, shortens its fibers which thus pulls the
      patella to the medial part of the femoral groove and keeps it in the trochlea
      during the initial 20 degrees -30 degrees of flexion.

PMID- 16001290
TI  - Moderate drought influences the effect of arbuscular mycorrhizal fungi as
      biocontrol agents against Verticillium-induced wilt in pepper.
AB  - Previous studies have shown that the arbuscular mycorrhizal fungus (AMF) Glomus
      deserticola (Trappe, Bloss and Menge) can diminish the negative effect of
      Verticillium dahliae Kleb. on pepper yield. On the other hand, it is known that
      AMF can be more beneficial for plant growth and physiology under dry conditions
      than when soil moisture is plentiful. Therefore, our objective was to assess if a
      moderate water deficit imposed on pepper plants before their inoculation with V.
      dahliae could improve the effectiveness of G. deserticola as biocontrol agent. In
      the present experiment, the delay in disease development in Verticillium
      inoculated plants associated with AMF did not occur under well watered
      conditions. In addition, the establishment of mycorrhizal symbiosis and the
      development of structures by AMF were delayed when both symbiotic and pathogenic
      fungi infected the same root. Therefore, it is suggested that the equilibrium
      between pepper plant, G. deserticola and V. dahliae is so complex that small
      changes in competition between symbiotic and pathogenic fungi for host resources
      can modify the efficiency of AMF as a biocontrol agent. On the other hand, water
      deficit enhanced the deleterious effect of V. dahliae on fruit set and yield only
      when pepper plants were not associated with G. deserticola, which reinforces the
      idea that AMF may be more important for host plants subjected to stressful
      conditions. However, comparing well watered non-mycorrhizal and predroughted
      mycorrhizal plants, we found that moderate water deficit imposed before
      inoculation with V. dahliae did not improve the effectiveness of G. deserticola
      as a biocontrol agent.

PMID- 16001291
TI  - Fracture prediction by bone density measurements at sites other than the fracture
      site: the contribution of BMD correlation.
AB  - It is widely believed that the most reliable BMD measurement for predicting
      fracture risk at any given skeletal site is one made at the fracture site itself.
      This study examines the hypothesis that the ability of BMD measurements at other
      distant sites in the skeleton remote from the fracture site to predict fracture
      risk is due to their correlation with the BMD measurements at the fracture site.
      We refer to this assumption as the correlation hypothesis. We show that the
      correlation hypothesis predicts the relationship betadist = rbetafrac, where beta
      is the gradient of the exponential relationship between fracture risk and Z
      score, betafrac is the beta-value for the fracture site, betadist the beta-value
      for the distant BMD site, and r is the correlation coefficient between the Z
      scores at the two sites. In practice it is important to consider the effect of
      BMD measurement errors on the (r, beta) relationship. We show that the effect of
      errors at the distant site is to reduce betadist and r in a way that preserves
      their original relationship. When errors at the fracture site are taken into
      account the effect on the (r, beta) plot is for the point representing the
      fracture site to fall below the extrapolation of the straight-line relationship
      predicted for the points representing the distant BMD sites. We tested the
      correlation hypothesis by using data from the Study of Osteoporotic Fractures to
      examine the (r, beta) plots for hip, spine and forearm fractures. For the hip the
      data are consistent with a straight-line relationship and suggest that
      measurements made at other sites provide no additional information about fracture
      risk over and above that provided by hip BMD itself. For spine and forearm
      fractures the data show that distant sites do provide additional information
      about fracture risk in a way that is quantitatively consistent with the BMD
      measurement errors reported in cadaver studies. It is clear that random BMD
      errors at the fracture site cause loss of information about fracture risk and
      that some of this lost information is recoverable from measurements made at other
      sites in the skeleton. Overall, this study points to BMD correlation as an
      important factor in explaining the ability of measurements made at distant sites
      to predict fracture risk.

PMID- 16001292
TI  - American Chemical Society - 221st National Meeting. Division of Medicinal
      Chemistry - Recent developments in PPARs. 1-5 April 2001, San Diego, CA, USA.

PMID- 16001293
TI  - 221st ACS. Division of Medicinal Chemistry - company focus.

PMID- 16001295
TI  - 221st ACS. Division of Medicinal Chemistry - Poster sessions.

PMID- 16001294
TI  - 221st ACS. Division of Medicinal Chemistry - natural products: nature's
      combichem.

PMID- 16001296
TI  - 221st ACS. Division of Medicinal Chemistry - general oral papers.

PMID- 16001297
TI  - 221st ACS. Division of Medicinal Chemistry - first-time disclosure of clinical
      candidates.
AB  - The 221st ACS meeting in San Diego, USA, saw a symposium entitled 'First-time
      disclosure of clinical candidates', the inaugural presentation of this symposium
      in the society's 125-year history. Dr Balu N Balasubramanian (Bristol-Myers
      Squibb Co, USA), Chair of this well-attended symposium of five papers, remarked
      that he hoped that this symposium will become a regular event at ACS conferences.

PMID- 16001298
TI  - 221st ACS. Division of Medicinal Chemistry - proteinase-activated receptor
      antagonists.

PMID- 16001299
TI  - 221st ACS. Division of Medicinal Chemistry - orphan nuclear receptors.

PMID- 16001300
TI  - 221st ACS. Division of Medicinal Chemistry - inhibitors of HIV entry: potential
      new therapies for treatment of HIV infection.

PMID- 16001301
TI  - 221st ACS. Division of Medicinal Chemistry - accelerating drug discovery:
      developments in ADME/Tox technologies.

PMID- 16001302
TI  - American Academy of Allergy, Asthma and Immunology - 57th Annual Meeting.
      Advances in treatment of allergic diseases: an update. 16-21 March 2001, New
      Orleans, LA, USA.

PMID- 16001303
TI  - 57th AAAAI. Oligodeoxynucleotides.
AB  - This meeting was notable for its eclectic approach to the field of Allergy and
      Clinical Immunology. There were plenary sessions on the management of asthma,
      anaphylaxis, and rhinitis, and workshops that dealt with each of these fields in
      depth. In addition, a number of sessions were devoted to the management of
      anaphylaxis, food allergy, urticaria, angioedema, and atopic dermatitis. There
      were research reports and clinical trials of antihistamines, corticosteroids,
      beta-adrenergic agents, leukotriene antagonists, and combination agents. For
      example, there were over 20 reported trials on inhaled corticosteroids either for
      rhinitis or asthma, and a similar amount presented regarding antihistamine
      therapy, antileukotriene therapy, and beta-adrenergic therapy. Emphasis was
      placed on the utilization of combination agents specifically montelukast (Merck)
      and loratadine (Schering-Plough) for the treatment of rhinitis, and
      formoterol/budesonide (AstraZeneca) and salmeterol/fluticasone (GlaxoSmithKline)
      for the therapy of asthma. Meetings were held from early morning (6.30) until the
      late evening (22.00).

PMID- 16001304
TI  - 57th AAAAI. Novel drugs.

PMID- 16001305
TI  - Cardiovascular pharmacotherapy - Tenth International Congress. 27-30 March 2001,
      Kyoto, Japan.

PMID- 16001306
TI  - Asthma: new drug targets and innovative therapeutics - SMi Conference. 28-29
      March 2001, London, UK.

PMID- 16001307
TI  - Neurotoxicity meeting - mechanisms for neurodegenerative disorders. 16-18 March
      2001, Pucon, Chile.

PMID- 16001308
TI  - Antifungal Drug Discovery & Development - Fifth International Summit. 28-29 March
      2001, Princeton, NJ, USA.
AB  - Reviews of recent clinical trials of marketed and investigational antifungal
      products revealed a number of recurring themes. There is currently a severely
      limited arsenal of antifungal drugs from which clinicians can choose. Many of the
      new products are improved versions or formulations of existing chemistries and
      modes of action, all of which still have some serious limitations, such as
      toxicity, insufficient solubility, rapid evolution of drug resistance, cost, and
      antagonisms when used in combination with other drug therapies. Specific
      sequential treatments with existing drugs appear to offer some promise, but
      problems in recruiting sufficient 'clean patients', who do not have many other
      health problems and complicated treatment histories, confounds such trials. Also,
      the current registration process requires the demonstration of efficacy as a
      single agent. Recent advances in the identification and validation of new drug
      targets, screening technologies and efficient exploitation of new chemistries
      from natural products appears to offer significant promise for the future. It
      will be of interest to see how quickly these advances in drug discovery result in
      new and improved antifungal drugs in commercial development pipelines.

PMID- 16001309
TI  - Society for general microbiology - 148th ordinary meeting. Activities and actions
      of antimicrobial peptides. 26-30 March 2001, Edinburgh, UK.
AB  - The rapidly expanding field of antimicrobial peptides is one that is attracting
      increasing interest from research groups around the world. The importance of
      antimicrobial agents in providing alternatives to conventional antibiotics has
      been highlighted in recent years by the emergence of a number of multidrug
      resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA)
      and vancomycin-resistant enterococci (VRE). Indeed, bacteria refractory to
      treatment by all known antibiotics are now a reality and the need for developing
      novel antimicrobial agents is urgent. This meeting brought together researchers
      working in a number of varied, but ultimately related areas. The functional
      diversity and putative mechanisms of action of antimicrobial peptides were
      discussed in depth, along with recent developments in the design of synthetic
      peptides with enhanced antimicrobial properties. Several ongoing studies were
      described, ranging from research into cystic fibrosis to work in the food
      industry. It was emphasized that cationic antimicrobial peptides have a range of
      properties to offer the world of scientific research and may play an important
      role in the ongoing battle against pathogenic microorganisms. Oral presentation
      sessions of the conference were co-chaired by Dr Deirdre A Devine (University of
      Leeds, UK) and Dr David G Smith (University of Edinburgh, UK).

PMID- 16001310
TI  - Cutting edge approaches to drug design. 13 March 2001, London, UK.

PMID- 16001311
TI  - alpha2-Adrenoreceptor antagonists.
AB  - A review of the literature relating to the therapeutic potential of alpha2
      adrenoceptor antagonists published between 1990 and 2000 is presented. Although
      extensively studied since the early 1970s in a wide spectrum of therapeutic
      applications, the distinction of alpha2-adrenoceptor subtypes and some emerging
      evidence concerning new applications in neurodegenerative disorders, such as
      Alzheimer's and Parkinson's diseases, obesity and schizophrenia, have refreshed
      an interest in this class of agents.

PMID- 16001312
TI  - Synthetic urokinase inhibitors as potential anti-invasive drugs.
AB  - In carcinogenesis, proteinases play an important role in metastasis of solid
      malignant tumors. Aside from several matrix metalloproteinases and cathepsins,
      the urokinase-plasmin system seems to be one of the main players within the cell
      surface-associated proteolytic activity, facilitating tumor cell migration and
      invasion. Upon binding to a specific receptor, the enzymatic activity of
      urokinase is focused to the cell surface. The significance of the plasminogen
      activator system in malignancy is underlined by the finding of elevated levels of
      urokinase and its receptor in tumor tissues. Therefore, the possible use of
      urokinase inhibitors in the therapeutic treatment of cancer and metastasis has
      been the subject of intensive investigations. This review covers synthetic
      inhibitors of urokinase described up to December 2000, although the number of
      lead structures is still relatively small.

PMID- 16001313
TI  - Male erectile dysfunction: therapy and drug delivery.
AB  - Finding an ideal chemical agent or a user-friendly delivery system for the
      treatment of male erectile dysfunction (MED) has been the goal of several
      research groups. The most suitable therapy for erectile dysfunction (ED) in man
      would involve a chemical that acts directly or indirectly on the penis and
      assures erection without any side effects. The understanding of ED has grown
      tremendously over the last decade and has been accompanied by an impressive
      proliferation of new therapies, ranging from traditional therapeutic agents to
      novel agents and drug delivery systems. Before Viagra, the most effective
      therapies involved injecting drugs directly into the base of the penis and
      inserting suppositories into the urethra, but these were too invasive to achieve
      great popularity. Although ED was not an area of pharmaceutical research that
      many companies were focused on, the success of Viagra has shown that there is a
      huge market opportunity for this indication. Financial analysts project a
      worldwide market of approximately $2 billion for oral ED treatments. This review
      presents a general overview of the present state as well as the future directions
      of research to treat MED.

PMID- 16001314
TI  - Efegatran. Institute for drug research/IVAX.
AB  - Efegatran is a thrombin inhibitor which is being developed by IVAX for the
      potential treatment of thromboembolic disorders [343400]. Efegatran was
      synthesized by the Hungarian Institute for Drug Research (IDR), which conducted
      phase II trials for angina in Hungary, and phase II trials for thrombosis in
      collaboration with Lilly in the US [182552]. However, nodevelopment has been
      reported by Lilly since IDR was taken over by IVAX in 1999 [343400]. In phase
      I/II trials in patients with unstable angina, the drug produced a dose-dependent
      increase in clotting time [279819]. In preliminary dose-ranging trials in
      unstable angina, the compound had a similar efficacy to heparin at the highest
      dose studied (0.1mg/kg bolus plus a 48 h infusion of 0.84 mg/kg/h).
      Thrombophlebitis was the only side effect observed [169368].

PMID- 16001315
TI  - Fomepizole (orphan medical).
AB  - Orphan Medical has developed fomepizole as a potential treatment for both
      ethylene glycol and methanol poisoning. The drug was launched as Antizol in
      January 1998 for the treatment of ethylene glycol poisoning [273949] after US
      marketing approval was grantedin December 1997 [271563]. It has also received US
      approval for methanol poisoning [393217] and UK approval for ethylene glycol
      poisoning [329495]. In 1999, Orphan Medical's partner, Cambridge Laboratories,
      intended to pursue European approval under the mutual recognition procedure
      [329495]. However, by September 2000, Cambridge Laboratories had discontinued
      their involvement with fomepizole and IDIS World Medicines had licensed the
      rights to distribute the drug in the UK [412142]. In February 2000, the Canadian
      Therapeutic Products Programme (TPP) granted fomepizole Priority Review, provided
      that an NDA was submitted by March 14, 2000 [354665]. In August 2000, the TPP
      accepted this NDA and set a target date for approval in the fourth quarter of
      2000 [379474]. The TPP granted fomepizole a Notice of Compliance permitting the
      sale of fomepizole in Canada in December 2000. The company's marketing partner in
      Canada, Paladin Labs had launched fomepizole by January 2001 [396953]. In June
      2000, Tucker Anthony Cleary Gull stated that the Orphan Drug status which Orphan
      Medical had obtained for fomepizole would provide marketing exclusivity through
      December 2004. The analysts also stated that fomepizole had accounted for 40% of
      Orphan Medical's revenue in financial year 1999, although +/- 30% of sales were
      estimated to be due to stockpiling [409606].

PMID- 16001316
TI  - [Old wine in new bottles -- did anaesthesiologists not yet organize
      economically?].

PMID- 16001317
TI  - [Business organization theory: its potential use in the organization of the
      operating room].
AB  - The paradigm of patient care in the German health system is changing. The
      introduction of German Diagnosis Related Groups (G-DRGs), a diagnosis-related
      coding system, has made process-oriented thinking increasingly important. The
      treatment process is viewed and managed as a whole from the admission to the
      discharge of the patient. The interfaces of departments and sectors are
      diminished. A main objective of these measures is to render patient care more
      cost efficient. Within the hospital, the operating room (OR) is the most
      expensive factor accounting for 25 - 50 % of the costs of a surgical patient and
      is also a bottleneck in the surgical patient care. Therefore, controlling of the
      perioperative treatment process is getting more and more important. Here, the
      business organisation theory can be a very useful tool. Especially the concepts
      of process organisation and process management can be applied to hospitals.
      Process-oriented thinking uncovers and solves typical organisational problems.
      Competences, responsibilities and tasks are reorganised by process orientation
      and the enterprise is gradually transformed to a process-oriented system. Process
      management includes objective-oriented controlling of the value chain of an
      enterprise with regard to quality, time, costs and customer satisfaction. The
      quality of the process is continuously improved using process-management
      techniques. The main advantage of process management is consistent customer
      orientation. Customer orientation means to be aware of the customer's needs at
      any time during the daily routine. The performance is therefore always directed
      towards current market requirements. This paper presents the basics of business
      organisation theory and to point out its potential use in the organisation of the
      OR.

PMID- 16001318
TI  - [Implementation of modern operating room management -- experiences made at an
      university hospital].
AB  - Caused by structural changes in health care the general need for cost control is
      evident for all hospitals. As operating room is one of the most cost-intensive
      sectors in a hospital, optimisation of workflow processes in this area is of
      particular interest for health care providers. While modern operating room
      management is established in several clinics yet, others are less prepared for
      economic challenges. Therefore, the operating room statute of the Charite
      university hospital useful for other hospitals to develop an own concept is
      presented. In addition, experiences made with implementation of new management
      structures are described and results obtained over the last 5 years are reported.
      Whereas the total number of operation procedures increased by 15 %, the operating
      room utilization increased more markedly in terms of time and cases. Summarizing
      the results, central operating room management has been proved to be an effective
      tool to increase the efficiency of workflow processes in the operating room.

PMID- 16001319
TI  - [Obturator nerve block for transurethral surgery. comparing ropivacaine 0.75 %
      vs. prilocaine 1 %].
AB  - OBJECTIVE: Obturator nerve block is used for transurethral resection of lateral
      bladder wall tumors to prevent adductor muscle spasm and associated
      complications. Therefore, the local anesthetic applied should provide an adequate
      motor blockade. Ropivacaine 0.75 % was compared to prilocaine 1 % and motor
      blockade assessment performed by the Medical Research Council (MRC)-scale.
      METHODS: 40 patients (20 per group) scheduled for transurethral resection were
      randomized to either receiving 10 ml ropivacaine 0.75 % or prilocaine 1 % for
      direct obturator nerve block in a controlled user-blinded study. Motor block was
      assessed with the MRC-scale 5 and 10 minutes after local anesthetic injection
      followed by an assessment 120 and 180 minutes after surgery. Surgery was
      performed in equally distributed spinal or general anesthesia, intraoperative
      adductor spasm intensity was evaluated by surgeon's ranking. RESULTS: Motor
      blockade intensity was significantly higher with ropivacaine 0.75 % at all time
      points of assessment. Intraoperatively, severe spasm only occurred in the
      prilocaine 1 %-group. CONCLUSION: Ropivacaine 0.75 % is a more appropriate agent
      for direct obturator nerve block than prilocaine 1 %, providing a faster onset
      and a more intense and longer-lasting motor blockade. This may reduce surgical
      complications and facilitate early surgical re-intervention. In this study, MRC
      scale was appropriate for motor blockade assessment in a peripheral nerve block.

PMID- 16001320
TI  - [Catecholamine-resistant hypotension -- an update].
AB  - Vasoplegia as catecholamine resistent hypotension occurs in severe hemorrhagic or
      septic shock and post cardiopulmonary bypass. The entire rational behind this
      phenomenon is still unclear. An ATP-shortage in the vascular musculature,
      disregulation of vasopressin release, and the activation of ATP-dependent
      potassium-channels are discussed. In the last years, attention is drawn towards
      the activation of ATP-dependent potassium-channels and the possible therapeutic
      inhibition by glibenclamid. However, inhibition of potassium-channels does not
      normalize blood pressure under all circumstances. In particular in septic shock
      other mechanisms have to be involved. Overall, the sometimes desperate clinical
      situation has led to a large number of case reports und uncontrolled series of
      retrospectively analysed cases, where vasopressin or methylenblue were discribed
      as successfully reversing catecholamine resistent hypotension. Nevertheless, in
      hemorrhagic and septic shock scientific evidence of the clinical effects and the
      right dose as well as placebo controlled studies comparing the agents and
      possible combinations of agents are desirable but hardly available yet. In the
      case of severe hypotension following surgery under cardiopulmonary bypass results
      of the first randomized and placebo controlled studies describe successful
      restoration of blood pressure and even a decrease in perioperative mortality.
      Concerning the side effects, vasopressin and methylenblue, like most
      vasopressors, can cause gastrointestinal ischemia, but with the small number of
      patients enrolled so far, further major side effects can not be ruled out.
      Accordingly, the identification of risk factors for the development of vasoplegia
      and the prediction of the extent of the response or the rate of non-responders to
      these treatments are widely unknown. However, although the administration of
      vasopressin and methylenblue can not be recommended as a standard treatment it
      provides an additional option in individual cases of life threatening vasoplegia.

PMID- 16001321
TI  - [Accidental intraartrial injection of diacethylmorphine (heroin) in drug addicts 
      - three case reports].
AB  - Accidental intrarterial injections are not uncommon in medical treatments. This
      is also true for uncontrolled injections by drug-addicts. Since 2002 a number of
      600 heavy opiate addicts in Germany are substituted in a country-wide study with
      pure diacetylmorphine (Heroine). We report the course and outcome of three cases
      of accidental intraarterial injections of pure diacetylmorphine under controlled
      conditions. After initial symptoms of vasospasms, all cases were without symptoms
      within one hour and no obvious loss of tissue was observed. After discussing the
      literature about medical literature and treatment options in intraarterial
      injections it is concluded, that the cause of major complications after
      intraarterial injections may not be the pure diacetylmorphine but additional
      substances in impure "street-heroin" samples.

PMID- 16001322
TI  - [End of life decisions in intensive care].

PMID- 16001325
TI  - Multiple endocrine neoplasias in the era of translational medicine.
AB  - Medicine is an ever changing art, continuously adjusting to the shifting
      principles of philosophy and constant discoveries of science; it was beautifully
      said by Hippocrates: "... medicine does not do the same thing at this moment and
      the next..." Unabated dissemination of information is the only way that patients
      are assured that physicians will continue to practice medicine that reflects
      contemporary science. In the field of Multiple Endocrine Neoplasias (MENs), this
      is at least in part accomplished by biennially held International Workshops. The
      articles led by this editorial are the second and last installment of a
      collection of state-of-the-art presentations given in the course of the ninth
      such workshop that was held in Bethesda, MD, June 19-22, 2004. In addition to
      serving as an introduction to the articles that were written by some of the
      leaders in the field, the text of the editorial review that follows also supports
      the notion that MENs are poised to lead translational research in endocrinology:
      these disorders have benefited remarkably from the discoveries of the human
      genome project and are at a unique position to take advantage of new modalities
      in basic and clinical science.

PMID- 16001326
TI  - Clinical and genetic features of familial pituitary adenomas.
AB  - Inherited or familial pituitary tumor syndromes such as multiple endocrine
      neoplasia type 1 and Carney complex provide an important insight into the
      genetics and molecular pathology of endocrine cancers. Our understanding of these
      conditions is expanding rapidly due to the identification of the genes and
      proteins affected and the availability of murine knockout models. The successes
      achieved to date in understanding multiple endocrine neoplasia type 1 and Carney
      complex have helped in the identification and study of new inherited pituitary
      tumor syndromes such as isolated familial somatotropinomas. This review assesses
      the current status of research into the clinical features, genetics and molecular
      pathologies of multiple endocrine neoplasia type 1, Carney complex, and isolated
      familial somatotropinomas, and details ongoing work to delineate familial
      isolated pituitary adenomas, a potentially new clinical entity.

PMID- 16001327
TI  - FGF receptor signaling at the crossroads of endocrine homeostasis and
      tumorigenesis.
AB  - Multiple endocrine neoplasia (MEN) syndromes represent familial disorders
      characterized by endocrine cell growth and hormone production dysregulation. For
      several decades, the fibroblast growth factor (FGF) system has been suspected of
      playing a unique function in MEN-type I (MEN I). However, specific elucidation of
      these actions has been hampered by the overwhelming redundancy of this complex
      system. The human FGF family is composed of 22 members organized into 6 groups
      based on phylogenetic relationships. Signaling is mediated through membrane
      spanning tyrosine kinase receptors encoded by four independent genes, some of
      which generate multiple products via alternative splicing or transcription
      initiation. High-affinity interaction between an FGF and its cognate receptor
      induces receptor dimerization and activation. Many FGFs display high-affinity
      interactions with multiple FGFRs, while some activate unique receptors or
      receptor isoforms. Most FGFs have demonstrated mitogenic activity in a variety of
      systems; however, a growing number display predominantly metabolic actions. This
      review will examine the evidence that FGF/FGFRs play a role in sporadic endocrine
      neoplasia and the pathways in which these molecules may be selectively targeted
      for therapeutic purposes.

PMID- 16001328
TI  - Epigenetic mechanisms of tumorigenesis.
AB  - In the majority of human cancers, heritable loss of gene function through cell
      division may be mediated as often by epigenetic as by genetic abnormalities.
      Epigenetic modification occurs through a process of interrelated changes in CpG
      island methylation and histone modifications. Candidate gene approaches of cell
      cycle, growth regulatory and apoptotic genes have shown epigenetic modification
      associated with loss of cognate proteins in sporadic pituitary tumors. A search
      for novel genes on the basis of their differential methylation has led to the
      isolation and functional characterization of a pro-apoptotic mediator--a
      pituitary tumor apoptosis gene ( PTAG). Although PTAG expression is significantly
      underexpressed in most pituitary adenomas, mechanisms in addition to methylation
      most likely account for its loss. The GNAS gene is imprinted in normal pituitary,
      and activating mutations within Gsalpha, referred to as the gsp oncogene, are
      almost invariably associated with the maternal expressed allele in somatotrophic
      adenomas. In addition, epigenetic modification, manifesting as relaxation of
      imprinting, leads to biallelic expression of Gsalpha irrespective of gsp status.
      Pituitary tumors as components of familial syndromes represent a rare entity, and
      the role of epigenetic modification in their evolution and outgrowth is not
      known. Although speculative, these studies might provide new insight since
      methylation-associated gene silencing is a feature of other familial tumor types.

PMID- 16001329
TI  - Menin molecular interactions: insights into normal functions and tumorigenesis.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease
      predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene.
      Biallelic loss of MEN1 resulting from small mutation and/or loss of
      heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary
      tumors. Mouse models of MEN1 underexpression or overexpression have also
      supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid
      protein encoded by MEN1, is expressed ubiquitously and found predominantly in the
      nucleus. Sequence analyses do not reveal motifs of known function other than two
      nuclear localization sequences. Menin has been found to partner in vitro with a
      variety of proteins that comprise transcription factors, DNA processing factors,
      DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin
      interactors suggest roles for menin in multiple biological pathways. Inactivation
      of menin switches its JunD partner from a downstream action of growth suppression
      to growth promotion. This is a plausible mechanism for menin tumorigenesis.

PMID- 16001330
TI  - Menin and TGF-beta superfamily member signaling via the Smad pathway in
      pituitary, parathyroid and osteoblast.
AB  - PITUITARY: Menin is a Smad3-interacting protein; inactivation of menin blocks
      transforming growth factor (TGF)-beta and activin signaling, antagonizing their
      growth-inhibitory properties in anterior pituitary cells. Menin is also required
      for the activin-induced inhibition of prolactin expression mediated by the Smads
      and the transcription factor, Pit-1. The interaction between menin and Smad3 is
      direct. PARATHYROID: In cultured parathyroid cells from uremic hemodialysis
      patients, in which the menin signaling pathways are probably still intact, menin
      inactivation achieved by menin antisense oligonucleotides leads to loss of TGF
      beta inhibition of parathyroid cell proliferation and parathyroid hormone (PTH)
      secretion. Moreover, TGF-beta does not affect the proliferation and PTH
      production of parathyroid cells from multiple endocrine neoplasia type 1 (MEN1)
      patients. OSTEOBLAST: Men1-null mouse fetuses that die at day 12 or earlier have
      cranial/facial hypoplasias implicating menin in bone development. Menin is
      required for the commitment of multipotential mesenchymal stem cells into the
      osteoblast lineage. This is achieved by menin interacting physically and
      functionally with bone morphogenetic protein (BMP)-2 regulated Smads, such as
      Smad1 and Smad5, and the key osteoblast regulator, Runx2. These interactions are
      lost as the committed osteoblasts differentiate further at which time menin
      interacts with Smad3, mediating the negative regulation of Runx2 by TGF-beta.
      Menin also suppresses osteoblast maturation, partly by inhibiting the
      differentiation actions of JunD.

PMID- 16001331
TI  - HRPT2, a tumor suppressor gene for hyperparathyroidism-jaw tumor syndrome.
AB  - Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a familial multi-tumor
      syndrome resulting from inactivating mutations in the HRPT2 tumor suppressor
      gene, which encodes a protein product named parafibromin. Here, we will review
      recent advances in genetic and protein studies on parafibromin, and examine its
      biological functions.

PMID- 16001332
TI  - New insights in the genetics of adrenocortical tumors, pheochromocytomas and
      paragangliomas.
AB  - Recent advances in the molecular genetic of adrenal tumors give new insights in
      the pathophysiology of these neoplasms in both hereditary and sporadic cases. The
      practice of genetic counselling in patients with adrenal tumors have been
      recently changed by the identification and the understanding of new specific
      hereditary cancer susceptibility syndromes. In the case of sporadic
      adrenocortical tumors these progress also offer new prognosis predictors. The
      genetic predisposition to adrenocortical cancer in children has been well
      established in the Li-Fraumeni and Beckewith-Wiedeman syndromes due to germline
      p53 mutation located at 17p13 and dysregulation of the imprinted IGF-2 locus at
      11p15, respectively. Adrenocortical tumors are also observed in Multiple
      Endocrine Neoplasia type I syndrome. Cushing's syndrome due to primary pigmented
      nodular adrenocortical disease have been observed in patients with germline
      PRKAR1A inactivating mutations. Interestingly allelic loss at 17p13 and 11p15
      have been observed in sporadic adrenocortical cancer and somatic PRKAR1A
      mutations in secreting adrenocortical adenomas. The potential interest of these
      finding for the diagnosis of these tumors will be discussed. In the case of
      pheochromocytoma and paraganglioma, the demonstration that three genes encoding
      three succinate dehydrogenase subunits (SDHD, SDHB, SDHC), belonging to the
      complex II of the respiratory chain in the mitochondria, are involved in the
      genetics of familial and especially in apparently sporadic phaeochromocytomas
      have dramatically modified our practice. Up to date, four diagnosis of familal
      disease (multiple endocrine neoplasia type II, von Hippel Lindau disease,
      neurofibromatosis type 1 and hereditary paraganglioma) should be discussed and
      causative mutations in six different phaechomocytoma susceptibility genes (RET,
      VHL, NF1, SDHB, SDHD, SDHC) could be identified. In this review, we will perform
      an update compiling these new clinical, genetic and functional data recently
      published. We will suggest guidelines for the practice of the phaeochomocytoma
      genetic testing in the patients and their families, and for an early detection of
      tumors in the patients or in individuals determined to be at-risk of disease by
      the presymptomatic genetic testing.

PMID- 16001333
TI  - Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma:
      diagnostic and therapeutic management.
AB  - There is evidence for a close interrelation between the adrenomedullary and
      adrenocortical tissues, and there are well-characterized models of their
      paracrine interaction. To contribute to the studies of systemic interactions
      between these tissues, we studied a 52-year-old female patient with a
      pheochromocytoma and a contralateral cortisol-producing adenoma. Due to a
      misunderstanding, she presented to her family doctor to have an inherited kidney
      disease ruled out. An adrenal mass was discovered incidentally by ultrasound. A
      computerized tomography of the abdomen revealed bilateral adrenal masses. Due to
      excess catecholamine secretion, bilateral pheochromocytomas based on multiple
      endocrine neoplasia syndrome were suspected. Laboratory work-up, selective
      adrenal venous sampling and magnetic resonance imaging studies established the
      diagnosis of a pheochromocytoma in the right-hand adrenal gland and a cortisol
      producing adenoma on the left. Simultaneous bilateral laparoscopic subtotal
      adrenalectomy was performed. Immunohistochemistry showed positive staining
      against chromogranin A in a histological specimen obtained from the right-hand
      adrenal gland, while the left was negative; the left-hand adrenal gland stained
      positive against the ACTH receptor (MC2R) while the right was negative.
      Genetically, the patient was negative for MEN2, von Hippel-Lindau disease, and
      mutations in subunits B, C, and D of the succinate dehydrogenase gene. Although
      presence of bilateral adrenal adenomas or bilateral adrenal pheochromocytomas in
      certain inherited disorders are possible, this rare case of an adrenal
      pheochromocytoma combined with a contralateral cortisol-producing adrenal adenoma
      may further underline the wide range of complex interactions between the two
      endocrine systems.

PMID- 16001334
TI  - [PSA level--is 4.0 ng/ml as upper limit too high].

PMID- 16001335
TI  - [Acute renal failure in sepsis. Strategies for prevention].

PMID- 16001336
TI  - [Reliable surgical procedure. Orthotopic bladder replacement in radical
      cystectomy].

PMID- 16001337
TI  - [The role of pelvic lymphadenectomy in the therapy of prostate and bladder
      cancer].
AB  - The rationale for locoregional staging lymphadenectomy in prostate cancer lies in
      the accurate diagnosis of occult micrometastases in order to stratify patients
      who might benefit from adjuvant therapeutic measures. In prostate cancer,
      extended pelvic lymphadenectomy (EPLA) including the lymphatic tissue along the
      common iliac region with the ureteral crossing as cranial margin, external and
      internal iliac region and the obturator fossa, has been shown to increase the
      yield of both total lymph nodes and lymph node metastases significantly. The
      total number of lymph nodes removed is about 2- to 3-fold higher and the
      frequency of micrometastatic lymph nodes is approximately 2-fold higher compared
      to standard lymphadenectomy. Furthermore, the frequency of observed positive
      lymph nodes in clinically localized and locally advanced prostate cancer is
      significantly higher than predicted by nomograms such as Partin tables and CART
      analysis. Although there are no prospective randomized trials demonstrating a
      survival benefit associated with EPLA, there might be an advantage for those with
      minimal lymph node involvement. Progression-free survival is significantly
      improved in patients undergoing EPLA with a 35 % benefit compared to standard
      lymphadenectomy. Various studies have documented an equal risk of cancer
      associated mortality in patients with no or only 1 - 2 positive lymph nodes.
      Since the surgery-associated morbidity of EPLA is not increased as compared to
      standard lymphadenectomy, EPLA should be favoured at least for all intermediate
      and high risk patients undergoing radical prostatectomy; in low risk patients the
      option of EPLA has to be discussed thoroughly. For the future, ongoing
      prospective trials have to demonstrate a clear benefit in terms of biochemical
      free and cancer-specific survival. With regard to muscle-invasive bladder cancer,
      it has been shown that lymph node dissection along the external, internal and
      common iliac artery and obturator fossa achieves accurate data for a valid
      locoregional staging. Only if frozen section analysis reveals metastatic deposits
      along these areas an extension of the lymphadenectomy including the aortic
      bifurcation up to the inferior mesenteric artery seems to be of additional
      diagnostic value. Various studies have demonstrated that extended pelvic
      lymphadenectomy results in an improvement of progression-free survival, however
      no significant benefit with regard to cancer-specific and overall survival has
      been demonstrated. Nevertheless, pelvic lymphadenectomy remains one of the most
      significant prognosticators with regard to relapse rates as has been demonstrated
      recently and, therefore, it should be performed thoroughly and anatomically
      adequate.

PMID- 16001338
TI  - [Subjective patient satisfaction after injection of botulinum-a toxin in detrusor
      overactivity].
AB  - PURPOSE: The established treatment for overactive detrusor function consists of
      anticholinergic drugs. But this treatment can fail or produce intolerable side
      effects. We therefore investigated the effect of botulinum-A toxin in treating
      overactive detrusor function in patients with neurogenic and nonneurogenic
      bladder dysfunction. We were particularly interested in patient satisfaction with
      this therapy. MATERIAL AND METHODS: The subjects were 38 patients who had
      overactive detrusor function of different origins and in whom therapy with
      anticholinergic drugs had failed. To measure results, we used urodynamic studies
      and a questionnaire that consisted of 27 validated questions ("Urogenital
      Distress Inventory UDI-6", "Symptom Severity Index" and "Symptom Impact Index")
      as well as a satisfaction questionnaire. We injected 200 - 300 U of botulinum-A
      toxin (Botox) cystoscopically. RESULTS: At least 4 weeks after injection, 90 % of
      the patients reported clear improvement of their voiding situation and 93 %
      stated that they would undergo this procedure again. The frequency of micturition
      decreased by 29 % in average, and the increased postvoid residual volume was
      clinically irrelevant. Patients reported side effects or complications in 6.7 %
      of cases. The satisfaction scale (0 - 10) averaged 6.9. Urodynamically, reflex
      volume increased by 85 %, maximal bladder capacity increased by 47 %, and bladder
      pressure decreased by 33 %. CONCLUSIONS: Botulinum-A toxin injection into the
      overactive detrusor muscle seems to be very effective. The effect is not only
      reflected in urodynamic studies but also in the subjective patient satisfaction.

PMID- 16001339
TI  - [Pudendal nerve stimulation therapy of the overactive bladder -- an alternative
      to sacral neuromodulation?].
AB  - PURPOSE: Sacral neuromodulation is known to be an alternative therapeutic option
      for patients with anticholinergic resistant overactive bladder (OAB). For the
      same indication, a microstimulation system called BION is available since last
      year. The BION-stimulator, which only measures 2.8 x 0.3 cm, is designed for
      pudendal nerve stimulation. Its implantation technique as well as the first
      clinical results are presented and discussed. MATERIALS AND METHODS: During an
      outpatient percutaneous screening test (PST), a pudendal nerve stimulation is
      performed with a needle electrode in local anesthesia. A 50 % increase in the
      urodynamic parameters (bladder capacity, first desire to void, compliance, etc.)
      is an indication for a chronic implantation of the BION stimulator, which also
      can be placed in local anesthesia. RESULTS: Two patients have been treated with a
      BION-stimulator in our clinic so far. Patient I suffered from an OAB with
      frequent urinary incontinence and patient II had a sensory OAB with high voiding
      frequency. After the BION(R)-implantation, patient I showed a reduction in
      incontinence episodes by 31.5 % a day and patient II had lowered voiding
      frequencies from 12.6 to 7 a day. The postoperative urodynamic investigations
      confirmed these clinical results. CONCLUSIONS: The BION-system and chronic
      pudendal nerve stimulation seem to be alternatives to sacral neuromodulation,
      however, patient selection is difficult as subchronic stimulation for a longer
      period of time is not possible so far.

PMID- 16001340
TI  - [Pain therapy of urologic tumors -- prophylaxis and therapy of side effects].
AB  - Pain is a cardinal symptom in 70 % of cancer patients. Even in developed
      countries, 30 to 80 % of these patients are inadequately treated. The main cause
      for this lack of care is not pain refractory to treatment but inadequate or
      incorrect use of analgesic drugs. A sufficient treatment of pain requires
      knowledge of the pathomechanism of pain and of the basics of pain management in
      cancer patients. The choice of analgesic drugs follows the WHO-recommended
      increase based on need. As long as possible, analgesic drugs should be given
      orally following a strict schedule and pre-emptively prior to renewed pain. The
      non-opioids are a heterogeneous group of drugs with different actions and side
      effects. Maximum doses exist for this group and weak opioids. A change to strong
      opioids is indicated when weak opioids fail to achieve sufficient pain control
      despite titration to the maximum dose. No upper limit exists for strong opioids
      and their use is limited by the side effects. The most frequent side effects are
      initial emesis and vomiting as well as long-lasting constipation. For this
      reason, most patients should be prescribed a temporary antiemetic and a laxative
      on a permanent basis.

PMID- 16001341
TI  - [Xanthogranulomatous pyelonephritis: presentation of an unusual case].
AB  - INTRODUCTION: Xanthogranulomatous pyelonephritis is a morphologically and
      clinically unique manifestation of chronic pyelonephritis with the formation of
      pus or granulomas. The most frequent predisposing factors for the development of
      xanthogranulomatous pyelonephritis are urinary obstruction (e. g., stones,
      tumors, congenital anomalies and functional impairment) and infection of the
      collecting system. CASE REPORT: We describe a 2-year-old female patient with
      unclear abdominal complaints, diarrhea, malaise, loss of appetite, weight loss,
      pale skin color, and recurrent and undulating fever in the presence of known left
      nephrolithiasis. Based on the clinical examination and imaging, above all, CT,
      the presumptive diagnosis of xanthogranulomatous pyelonephritis of the left
      kidney was made. A left lumbar nephrectomy was performed and histology confirmed
      the diagnosis. CONCLUSION: Xanthogranulomatous pyelonephritis is a relatively
      rare entity that is associated with obstruction (e. g., stones) and infection of
      the urinary tract. Its rarity and resultant unfamiliarity often delay diagnosis
      and therapy, which in turn affect the prognosis. Furthermore, this entity can be
      mistaken for renal tumors (renal cell carcinoma and Wilms tumor), but nowadays
      this should be mostly eliminated with the advances in the imaging methods.

PMID- 16001342
TI  - [Foreign body in the urinary bladder after vascular surgery].
AB  - INTRODUCTION: We are presenting a rare complication after femorofemoral bypass
      surgery. CASE REPORT: In a 61-year-old male patient, a femorofemoral crossover
      bypass graft was inadvertently placed through the urinary bladder.
      Postoperatively, the patient developed macrohematuria, which cleared
      spontaneously. The diagnosis of an intravesical graft was made 3 months after
      surgery by cystoscopy performed because of dysuria. The patient underwent open
      bladder surgery 7 months later as he refused earlier intervention. The misplaced
      graft, which was not infected and showed good function and perfusion, was
      extravesically relocated. At a 16-month follow-up examination, the patient is
      free of urological symptoms and the bypass functions well. CONCLUSIONS: In case
      of dysuria or macrohematuria after vascular surgery in the vicinity of the
      urinary bladder, a misplaced bypass should be excluded.

PMID- 16001343
TI  - [Transurethral electroresection of the prostate].

PMID- 16001344
TI  - [Internal urethrotomy].

PMID- 16001345
TI  - Hepatic arterial doppler sonography in patients with cirrhosis and controls:
      observer and equipment variability with use of the ultrasonic contrast agent SHU
      508A.
AB  - PURPOSE: The aims of this study on hepatic arterial Doppler sonography were to
      ascertain interobserver and interequipment variability, to investigate any
      potential artificial influence of the ultrasonic contrast agent on the Doppler
      measurements and to compare the results in healthy and cirrhotic subjects.
      METHODS: Doppler sonography of the left hepatic artery was performed in nine
      healthy and nine cirrhotic subjects by three independent observers using three
      different devices. Continuous infusion of the ultrasonic contrast agent SHU 508A
      and placebo were administered in a double blind fashion. Systolic, mean and end
      diastolic peak velocities as well as resistive and pulsatility indices were
      measured. RESULTS: Equipment associated variances (5.8 - 12.7 %) of the five
      Doppler parameters were greater than interobserver variances (0.3 - 3.6 %). No
      significant differences were observed between the velocities using ultrasonic
      contrast agent and placebo. Systolic (65.9 +/- 3.6 vs. 47.7 +/- 4.2 cm/s mean +/-
      SE, p = 0.02) and mean peak velocity (35.4 +/- 1.6 vs. 24.5 +/- 1.8 cm/s, p =
      0.007) were significantly higher in cirrhotic than in healthy subjects whereas
      the resistive and pulsatility indices were not different. CONCLUSIONS: Doppler
      sonography of the left hepatic artery performed by various observers is
      reproducible as long as the same device is used. Under clinical conditions,
      velocities are correctly measured with the use of ultrasonic contrast agent and
      are elevated in patients with cirrhosis.

PMID- 16001346
TI  - [Evaluation of outpatient management in HNPCC].
AB  - The differential diagnostic assignment of patients with hereditary non-polyposis
      colorectal cancer among patients with non-familial colorectal carcinoma is
      difficult but essential to provide early sufficient cancer screening. In order to
      analyze the actual situation of outpatients, 36 gastroenterologists in private
      practice have been interviewed with respect to their experience concerning
      outpatients. The interview data revealed that care for patients with colorectal
      cancer is a fundamental component of their work. A third of the
      gastroenterologists deal with patients suffering from colorectal cancer before 45
      years of age. Yet these gastroenterologists did not report a single HNPCC
      patient. Especially gastroenterologists with long lasting experience in private
      practice did not mention HNPCC patients at all. These results may indicate that
      identifying the cases at risk for HNPCC is difficult in daily routine work. The
      possibility of genetic diagnostics (and counselling) should be taken into
      consideration in individual cases. In consequence comprehensive screening
      programs can be initiated for patients and their families.

PMID- 16001347
TI  - Giant fold gastritis with consecutive gastric carcinoma in a patient with peutz
      jeghers syndrome.
AB  - We describe the case of a 36-year-old patient with Peutz-Jeghers syndrome and a
      very unusual gastric morphology resembling giant fold gastritis. The latter
      lacked additional features of Menetrier's syndrome, was not influenced by
      eradication of Helicobacter pylori and persisted for more than ten years under
      regular endoscopic surveillance. Histologically, foveolar hyperplasia was found
      in the enlarged folds. Endoscopic ultrasound documented a hyperechoic widening of
      the gastric mucosa without involvement of the deeper layers. However, despite
      annual control gastroscopies, an adenocarcinoma developed between the folds and
      was in an already advanced stage at diagnosis (UICC III). We suggest that a
      variant of Peutz-Jeghers syndrome may be characterised by marked foveolar
      hyperplasia similar to Menetrier disease, and that not conventional endoscopy
      alone, but rather endoscopic ultrasound may be considered in such patients.

PMID- 16001348
TI  - Lansoprazole-associated collagenous colitis: a case report.
AB  - A 57-year-old man developed chronic, watery diarrhea four weeks after
      Helicobacter pylori eradication therapy including lansoprazole followed by
      lansoprazole monotherapy for gastroesophageal reflux disease. Four weeks later
      the patient was admitted to our hospital. By repeated testing other causes of
      diarrhea, e. g., infectious diarrhea including Clostridium difficile colitis were
      excluded. Endoscopy showed a normal colon, histopathology of random biopsies of
      all sections of the colon demonstrated the characteristic features of collagenous
      colitis. Withdrawal of lansoprazole lead to prompt and sustained relief. Two
      months later repeat colonoscopy with biopsies showed no evidence of collagenous
      colitis. Collagenous colitis as a subtype of microscopic colitis is a rare cause
      of chronic diarrhea with unknown pathogenesis. The reported case represents an
      unusual association between medication with the proton pump inhibitor
      lansoprazole and the development of collagenous colitis suggesting the importance
      of evaluation of drug use in patients with microscopic colitis.

PMID- 16001349
TI  - [Clinical management of patients with short bowel syndrome].
AB  - Diarrhoea, malabsorption and malnutrition characterise the short bowel syndrome.
      The underlying gastrointestinal disorders, the types of intestinal resections
      performed and the subsequent pathophysiological situations are reviewed.
      Recommended therapeutic measures in the postoperative period as well as in the
      rehabilitation of patients with short bowel syndrome are discussed in more
      detail. In the postoperative period, parenteral nutrition is essential followed
      by an enteral diet to stimulate bowel adaptation, reduce fluid loss and increase
      nutrient absorption. The final diet should be based on the anatomy of the
      retained bowel (presence or absence of a colon and ileum). The importance of the
      colon as a digestive organ in patients with short bowel and the need of a low
      oxalate diet are underlined. The possible benefit of new treatment options
      (glutamine, growth hormone and glucagon-like peptide 2) is discussed. Both
      typical complications of the short bowel syndrome and management of these
      complications are presented.

PMID- 16001351
TI  - [Acid suppression -- increased risk for pneumonia: resuscitation of an already
      refuted concept?].

PMID- 16001350
TI  - [Portopulmonary hypertension].
AB  - Patients with portal hypertension may develop pulmonary complications such as
      hepatopulmonary syndrome (HPS) or portopulmonary hypertension (PPHT). PPHT is
      defined as elevated pulmonary pressure, elevated pulmonary vascular resistance, a
      normal pulmonary capillary wedge pressure, and portal hypertension in the absence
      of other known causes pulmonary hypertension. Various factors such as
      hyperdynamic circulation, volume overload, and circulating vasoactive mediators
      are suspected to be involved in the pathogenesis of PPHT. The prognosis of
      patients with severe PPHT is significantly reduced due to the risk of right heart
      failure. In patients with moderate to severe PPHT liver transplantation is
      associated with a significantly increased mortality. The chief symptom of PPHT
      may be dyspnoe in the presence of typical histomorphological alterations
      comparable with idiopathic pulmonary hypertension. Continuous intravenous
      application of prostacyclin is currently regarded as the treatment of choice for
      patients with severe PPHT. Inhaled prostacyclin or its analogue iloprost or oral
      treatment with the endothelin-receptor antagonist bosentan may be promising
      alternatives which should be further investigated in randomized controlled
      trials.

PMID- 16001352
TI  - [Adalimumab in infliximab refractory Crohn's disease -- the next generation of
      anti-TNF-alpha-therapy?].

PMID- 16001353
TI  - [Further development of the diagnosis-related groups system--fact or fiction?
      Differentiation of case severities in patients with proximal femoral fractures
      2003-2005].
AB  - BACKGROUND: The previous system of hospital financing based on the returns
      (consisting of payments received minus cost of patient treatment) is undergoing
      considerable changes on the basis of learning to apply the new Diagnosis-Related
      Groups (G-DRG) system which differentiates the financial returns according to the
      individual severity of each case. AIM OF THE STUDY: 1. What are the differences
      in cost and returns when applying the G-DRG systems 2003, 2004 and 2005 to well
      defined groups of patients (for example, surgery of proximal femoral fractures)?
      2. The influence exercised by secondary (supplementary) diagnosis on the grouping
      of the patients. 3. Has the G-DRG system been appropriately developed further in
      respect of improved differentiation according to severity of the cases and
      homogenisation of the patient groups? PATIENTS AND METHODS: The study was based
      on comprehensive clinical data of 169 proximal femur fracture patients. We
      assessed the Case-Mix index, relative weights and returns, basic DRG, DRG, the
      number and weight of secondary diagnoses relevant for complexity and comorbidity
      levels (CCL), the summands of the CCL's and the resulting PCCL values (Patient
      Clinical Complexity Levels). The data were subjected to analysis of variance and
      graphically descriptive analysis. RESULTS: The effective Case Mix index decreases
      in the 2004 and 2005 systems compared to 2003. This is due to a significant drop
      in returns based on an unchanged rate of receipts of 3000 . The progressive
      development of the systems was partly associated with major changes in grouping
      without significant intra-group homogenisation or improved inter-group
      discrimination of indications. The differentiation process does not fully utilise
      the differentiation potential of the basic data. CONCLUSIONS: No definite
      improvement of the differentiation potential of the G-DRG systems seems to have
      been achieved by the 2004 and 2005 systems compared to 2003 using the data of the
      relevant group of patients with proximal femoral fractures. From 2005 onward the
      financial lumpsum receipts and returns will definitely affect hospital budgets.
      Hence, a substantial improvement of the the basis of calculation is imperative
      for 2005 as well as complete publication of the relevant data. It is indeed
      doubtful whether the extension of the convergence phase to 5 years presently
      under discussion would provide sufficient time for an adequate solution of the
      financial and system problems.

PMID- 16001354
TI  - [Consequence of evidence-based medicine and individual case appraisal of the
      Robodoc method for the MDK, and the malpractice management of insurance funds and
      the principles of managing innovations].
AB  - PURPOSE: Robots in Total Hip Replacement were introduced to utilize the precision
      of an industrial robot for reaming the femur. This method has been discussed
      controversially from the beginning of its clinical application in Germany.
      Criticism increased recently especially in respect of alleged malpractice. Aim of
      this study was to describe the consequences of the results of a systematic review
      and the evaluation of malpractice accusations for statutory health insurance and
      medical advisory services. METHOD: Robot-assisted total hip replacement was
      evaluated by a Health Technology Assessment report, especially concerning proof
      of clinical benefit and specific complications of this method. 44 cases of
      alleged malpractice reported to health insurance were assessed as well and
      compared with the results of the systematic review. RESULTS: The HTA report
      showed no proof of clinical benefit but pointed to increased rates of
      complications. In the 44 evaluated cases the entire range of endoprosthesis- but
      no robot-specific complications could be identified. CONCLUSION: Patients must be
      informed about risks, complications, benefits and especially alternatives to a
      robot-assisted operation. The prospective procedure of management of assumed
      malpractice concerning Robodoc can not be standardised, but each case must be
      evaluated individually. Consequently, implementation of a structured malpractice
      management system for health insurance and medical advisory services should be
      useful. Additionally, health service should implement an "early warning system"
      for innovative procedures.

PMID- 16001355
TI  - [Guidelines for the sociomedical assessment of performance in patients suffering
      from inflammatory bowel disease].
AB  - The following guidelines were developed for the medical assessment services of
      the German Federal Insurance Institute for Salaried Employees (BfA). Starting
      from day-to-day practice, criteria and attributes to guide decisions for a
      systemization of the sociomedical assessment of performance in inflammatory bowel
      disease (Crohn's disease, ulcerative colitis) were compiled. The guidelines aim
      at standardising the sociomedical assessment of performance and help to make the
      decision-making process more transparent -- e. g. for the assessment of
      applications for decreased earning capacity benefits. The guidelines summarise
      typical manifestations of inflammatory bowel disease and describe the necessary
      medical information for the sociomedical assessment of performance. Relevant
      assessment criteria for the medical history, clinical examination, and for
      diagnostic tests are illustrated. The assessment of the individual's capacity is
      outlined, taking occupational factors into account. Following the determination
      of dysfunctions the remaining abilities and disabilities, respectively, are
      deduced and compared with occupational demands. Finally, inferences are drawn
      regarding the occupational capacity of the individual.

PMID- 16001356
TI  - [GPS--good practice secondary data analysis. Working Group for the Survey and
      Utilization of Secondary Data (AGENS) of the German Society for Social Medicine
      and Prevention (DGSMP)].
AB  - The scientific use of secondary data, especially of claims data from health
      insurance funds, has continuously increased in the last years. Therefore the
      Working Group "Collection and Use of Secondary Data" (AGENS) of the German
      Society of Social Medicine and Prevention (DGSMP) took the initiative to define
      quality standards for secondary data analysis. Starting with a review of the Good
      Epidemiologic Practice (GEP) AGENS adapted the GEP to the specific requirements
      of secondary data analysis by a multi-stage consensus process. The guideline Good
      Practice Secondary Date Analysis (GPS) was adopted on January 15 (th), 2005. GPS
      consists of 10 guidelines which are divided in explaining comments and
      recommendations. The GPS are targeted to set up standards for secondary data
      analysis, and they may also be used as a foundation of contracts between data
      owners and scientists. They are addressed to scientists from health services
      research and social medicine. AGENS commits itself to revise GPS continuously.

PMID- 16001357
TI  - [Health Behaviour in school-aged children--results of the international study
      "Health Behavior in School-aged Children"].
AB  - INTRODUCTION: Childhood and adolescence are critical periods in the development
      and stabilisation of health behaviour and risk behaviour. Typically, individual
      health behaviour developed during this phase of life is carried into adulthood.
      The goal of this data analysis was to conduct an international comparison of
      adverse health behaviour among adolescents, to interpret differences between
      countries, and to make recommendations for future health promotion and prevention
      programmes. METHODS: The international comparative study "Health Behaviour in
      School-aged Children" (HBSC) serves as the basis for this data analysis. HBSC is
      conducted by the WHO (World Health Organization) every four years. The four
      health behaviour indicators selected from the HBSC study for this analysis
      include tobacco consumption, alcohol consumption, physical activity, and eating
      behaviour. RESULTS AND DISCUSSION: Large differences in adolescent health
      behaviour were identified among the countries of the EU and the USA. German youth
      when compared with youth in other countries, have higher rates for most selected
      indicators. To enhance success, prevention and health promotion programmes in
      Germany should adopt effective strategies from other countries, and include
      gender-specific and comprehensive programming aspects. Based on this comparison,
      it is recommended that health interventions should be tailored to the cultural,
      social, economic and political conditions of a particular country.

PMID- 16001358
TI  - [A comparison of different methods of performance assessment for the course in
      general medicine].
AB  - A novel Federal Regulation for Basic Medical Education was issued in Germany,
      which requires an end of course assessment. General Practice (GP) in Duesseldorf
      has introduced a written examination. An accompanying study was carried out to
      understand whether different methods of performance evaluation would show
      equivalent results intraindividually. Out of the GP class 21 students were
      randomised to undergo an oral examination on top of the regular written
      examination. Furthermore their teaching practitioners have appraised these
      students performance in small group teaching. Finally, the students have been
      rated following a practical term. At the end the students have been interviewed
      in a focus group to investigate their preferred method of assessment. The survey
      of the average grades showed comparable results for the written test, the oral
      examination and small group teaching while the appraisal at the end of the
      practical term happened to be significantly higher in grade. The comparison of
      the individual results, however, showed a statistical spreading in all
      directions. For example, a poor performance in the written test can come along
      with excellent results in the oral examination and vice versa. The intra-class
      correlation across all classes has been as low as 0.1. These results support the
      conclusion that apparently each method can appropriately evaluate only a very
      specific part of the complex contents of the GP education and of students'
      performance. In order to properly examine the performance of GP students a
      combination of different evaluation methods needs to be applied. As an
      alternative, different skills can be examined in different practical and
      theoretical test situations in an OSCE.

PMID- 16001362
TI  - An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is
      associated with a single-nucleotide substitution in the 5' untranslated region of
      the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide
      exchange-factor domains.
AB  - Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous
      neurodegenerative disorders. By positional cloning, we have identified the gene
      strongly associated with a form of degenerative ataxia (chromosome 16q22.1-linked
      ADCA) that clinically shows progressive pure cerebellar ataxia. Detailed
      examination by use of audiogram suggested that sensorineural hearing impairment
      may be associated with ataxia in our families. After restricting the candidate
      region in chromosome 16q22.1 by haplotype analysis, we found that all patients
      from 52 unrelated Japanese families harbor a heterozygous C-->T single-nucleotide
      substitution, 16 nt upstream of the putative translation initiation site of the
      gene for a hypothetical protein DKFZP434I216, which we have called "puratrophin
      1" (Purkinje cell atrophy associated protein-1). The full-length puratrophin-1
      mRNA had an open reading frame of 3,576 nt, predicted to contain important
      domains, including the spectrin repeat and the guanine-nucleotide exchange factor
      (GEF) for Rho GTPases, followed by the Dbl-homologous domain, which indicates the
      role of puratrophin-1 in intracellular signaling and actin dynamics at the Golgi
      apparatus. Puratrophin-1--normally expressed in a wide range of cells, including
      epithelial hair cells in the cochlea--was aggregated in Purkinje cells of the
      chromosome 16q22.1-linked ADCA brains. Consistent with the protein prediction
      data of puratrophin-1, the Golgi-apparatus membrane protein and spectrin also
      formed aggregates in Purkinje cells. The present study highlights the importance
      of the 5' untranslated region (UTR) in identification of genes of human disease,
      suggests that a single-nucleotide substitution in the 5' UTR could be associated
      with protein aggregation, and indicates that the GEF protein is associated with
      cerebellar degeneration in humans.

PMID- 16001361
TI  - How malaria has affected the human genome and what human genetics can teach us
      about malaria.
AB  - Malaria is a major killer of children worldwide and the strongest known force for
      evolutionary selection in the recent history of the human genome. The past decade
      has seen growing evidence of ethnic differences in susceptibility to malaria and
      of the diverse genetic adaptations to malaria that have arisen in different
      populations: epidemiological confirmation of the hypotheses that G6PD deficiency,
      alpha+ thalassemia, and hemoglobin C protect against malaria mortality; the
      application of novel haplotype-based techniques demonstrating that malaria
      protective genes have been subject to recent positive selection; the first
      genetic linkage maps of resistance to malaria in experimental murine models; and
      a growing number of reported associations with resistance and susceptibility to
      human malaria, particularly in genes involved in immunity, inflammation, and cell
      adhesion. The challenge for the next decade is to build the global
      epidemiological infrastructure required for statistically robust genomewide
      association analysis, as a way of discovering novel mechanisms of protective
      immunity that can be used in the development of an effective malaria vaccine.

PMID- 16001363
TI  - A genomewide scan for intelligence identifies quantitative trait loci on 2q and
      6p.
AB  - Between 40% and 80% of the variation in human intelligence (IQ) is attributable
      to genetic factors. Except for many rare mutations resulting in severe cognitive
      dysfunction, attempts to identify these factors have not been successful. We
      report a genomewide linkage scan involving 634 sibling pairs designed to identify
      chromosomal regions that explain variation in IQ. Model-free multipoint linkage
      analysis revealed evidence of a significant quantitative-trait locus for
      performance IQ at 2q24.1-31.1 (LOD score 4.42), which overlaps the 2q21-33 region
      that has repeatedly shown linkage to autism. A second region revealed suggestive
      linkage for both full-scale and verbal IQs on 6p25.3-22.3 (LOD score 3.20 for
      full-scale IQ and 2.33 for verbal IQ), overlapping marginally with the 6p22.3
      21.31 region implicated in reading disability and dyslexia.

PMID- 16001364
TI  - [Renal function, organic acid transport and protein binding: the three elements
      defining the response to diuretics in clinical practice: an update].
AB  - Organic anion transporters (OATs), which are expressed in proximal tubule cells,
      mediate diuretic secretion into tubular fluid. Increased plasma levels of organic
      anions and urate and metabolic acidosis, i.e. two characteristic features of
      chronic renal insufficiency, could be factors contributing to diuretic
      resistance. These limitations demand increasing doses of diuretics up to a
      maximum level, or the use of a loop diuretic with non-renal metabolism. Diuretic
      responsiveness in nephrotic syndrome is limited by strong Na+ reabsorption in the
      distal nephron. Strategies to improve loop diuretic responsiveness include
      diuretic dosage and the combination of a loop diuretic with a distal acting
      diuretic. Strategies to limit protein excretion include the use of angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers and appropriate
      salt intake limitation.

PMID- 16001365
TI  - [Contrast-induced acute renal failure].
AB  - The administration of radiocontrast media (RC) can lead to usually a reversible
      form of acute renal failure (ARF) that begins soon after the contrast is
      administered. A functional definition of RC-induced ARF varies among different
      studies: most commonly reported as a proportional rise in serum creatinine (Cr),
      25 or 50% above baseline or an absolute rise of 0.5-1.0 mg/dL within 48 hr after
      exposure to RC. Serum Cr returns to baseline over 8-12 days. Sometimes ARF is
      irreversible, contributing to an increase in mortality. Iodinated RC are either
      ionic or non-ionic and, at the concentrations required for arteriography or
      computed tomography, are of variable osmolality. Considering the main ARF risk
      factors, a rise in plasma Cr is: negligible with normal renal function, even if
      the patient is diabetic; 4-11% with mild to moderate renal insufficiency alone
      (plasma Cr between 1.5 and 4.0 mg/dL); 9-38% with mild to moderate renal
      insufficiency and diabetes mellitus; > or =50% if baseline plasma Cr is >4-5
      mg/dL, particularly in patients with diabetic nephropathy. This risk, however, is
      increased further by more advanced renal dysfunction, marked volume depletion,
      severe heart failure, or multiple contrast studies within 72-hr. Pathogenesis is
      not well understood, but the mechanism by which nephrotoxins induce renal injury
      is generally by either vascular or direct tubular effects. In the case of RC ARF,
      there appears to be an influence of both mechanisms, although altered renal
      hemodynamics predominates. Both are thought to occur from exposure to the
      hyperosmolar agent. The best treatment for contrast-induced renal failure is
      prevention. Some preventive measures include the use, if clinically possible, of
      ultrasonography, magnetic resonance imaging or CT scanning without RC agents,
      particularly, in high-risk patients; the use of lower contrast doses and the
      avoidance of frequent repetitive studies; the avoidance of volume depletion or
      non-steroidal anti-inflammatory drugs; the administration of intravenous saline
      and the antioxidant acetylcysteine; the use of low or iso-osmolal non-ionic
      contrast agents, particularly in high risk patients.

PMID- 16001366
TI  - [Imaging strategies for renovascular disease].
AB  - Renovascular disease (RVD) is detected with increasing frequency because with an
      aging population, atherosclerosis and its consequences are seen more frequently.
      RVD has three component parts: renal artery stenosis (RAS), renovascular
      hypertension (RVH), and ischemic nephropathy (IN). Each component should be
      recognized by the appropriate diagnostic tool. The proper techniques and
      procedures to establish an anatomical RAS diagnosis are: computed tomography
      angiography, magnetic resonance (MR) angiography and catheter angiography, which
      is the gold standard. The presence of RAS can also be disclosed through increased
      systolic blood flow velocity at the level of the narrowed renal artery by an echo
      color-Doppler. Once the presence of RAS is demonstrated the diagnosis of RVH
      and/or IN should be performed. The RVH diagnosis needs to demonstrate a causal
      link between RAS and blood pressure (BP) increase; a causal link between RAS and
      the reduction in glomerular filtration rate (GFR) is mandatory for the IN
      diagnosis. Techniques and procedures suggesting that BP is increased and/or GFR
      is reduced based on RAS are captopril enhanced renoscintigraphy, BP gradient
      across the stenosis, captopril modification of Doppler parameters and captopril
      modification of MR curves. The resistive index obtained by color-Doppler could be
      a structural damage marker of the intrarenal arterioles. A rational approach to
      the problem demands that each technique is chosen according patient clinical
      characteristics.

PMID- 16001367
TI  - [Historical Archives of Italian Nephrology. The gout as a paradigmatic example of
      the ancient humoral theory of diseases].
AB  - Gout is one of the oldest known diseases. The term derives from the Latin
      "gutta", which means "a drop" This word expresses and describes, as no other term
      can, a method of interpreting the pathologies that have been with us for more
      than 2000 yrs. The theory of humoral disturbance goes back to the time of
      Hippocrates. This paper is a historical review of gout, with particular attention
      given to the interpretation of the origins of clinical, articular and renal
      involvement allowing us paradigmatically to sum up all the stages in the
      evolution of the etiopathogenetic and nosographic concepts of medicine through
      the ages.

PMID- 16001368
TI  - [SIN survey on quality control of dialysis water in Italy].
AB  - BACKGROUND: The importance of high quality water for dialysis is well
      established. This study aimed to obtain a picture of the Italian situation to
      develop national guidelines. METHODS: Questionnaire analysis was used to assess
      water quality control protocols and types of chemical and microbiological
      parameters monitored. Regions with responses from at least half the units were
      considered for the study. RESULTS: Eighteen out of 20 regions fulfilled the
      inclusion criteria; 297/469 dialysis units answered the questionnaire (5208
      dialysis beds, 18213 patients). Eighty-one percent of Italian units follow a
      regular water quality control program. The reverse osmosis outlet is the sampling
      point used most for assessing chemical and microbiological parameters. The most
      common frequency in monitoring is < or =6 months. Fifteen chemical items,
      suggested by the Italian Farmacopea Ufficiale (FU), are periodically controlled
      by at least half the units. Aluminum is measured in about 70% of units,
      chloramines and volatile halogenated hydrocarbons, respectively, in 42 and 30% of
      units. According to the FU, bacterial counts at 22 degrees C (84%) and endotoxin
      determinations (60%) are the most common microbiological analyzes. CONCLUSIONS:
      The survey demonstrated protocol differences among the units, confirming the need
      for Italian guidelines to ameliorate and standardize dialysis water monitoring.
      More than half the units are following the FU, but we cannot rule out less strict
      monitoring only in non-participating units.

PMID- 16001369
TI  - [Guidelines on water and solutions for dialysis. Italian Society of Nephrology].
AB  - The National Society of Nephrology has promoted the development of specific
      Italian Guidelines for dialysis fluids. Two previous national inquiries showed a
      wide variety in the type and frequency of both microbiological and chemical
      controls concerning dialysis water, reinforcing the need for specific standards
      and recommendations. An optimal water treatment system should include tap water
      pre-treatment and a double reverse osmosis process. Every component of the
      system, including the delivery of the treated water to the dialysis machines,
      should prevent microbiological contamination of the fluid. Regular chemical and
      microbiological tests and regular disinfection of the system are necessary. 1.
      Chemical quality (Table: see text). Treated tap water used to prepare dialysis
      fluid should be within European Pharmacopoeia limits at the water treatment
      system inlet and at the reverse osmosis outlet. In addition dialysate,
      concentrate and infusion fluids must comply with specific Pharmacopoeia limits.
      The physician in charge of the dialysis unit is advised to institute a
      multidisciplinary team to evaluate the requirement for added chemical controls in
      the presence of local hazards. 2. Microbiological quality (Table: see text). High
      microbiological purity of dialysis fluid--regularly verified--is a fundamental
      prerequisite for dialysis quality and every dialysis unit should aim as a matter
      of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL,
      endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular
      disinfection of dialysis machines greatly enhance microbiological purity. On-line
      dialysate reinfusion requires specific devices used according to corresponding
      instructions and to more frequent microbiological tests. Dialysis fluids for home
      dialysis should comply with the same chemical and bacteriological quality. The
      appendix reports the water treatment system's technical characteristics, sampling
      and analytical methods, monitoring time-tables, as well as the origin and effects
      of the main toxic substances. Suggestions and questions concerning these
      guidelines are welcome to nefrologia@sin-italy.org.

PMID- 16001370
TI  - [From the Mailing List SIN: Therapy and prevention of peritoneal sclerosis].
AB  - Recently, in the Mailing List of the Italian Society of Nephrology (ML-SIN), a
      message asking for opinions on the diagnosis and treatment of peritoneal
      sclerosis gave rise to an extensive debate on this interesting clinical topic.
      The discussion evidenced significant differences both in the reported onset of
      clinical manifestations, emphasizing the difficulty in obtaining a definite early
      diagnosis, and in therapy approaches. Occasionally, this is limited to medical
      treatment, but surgery, although burdened with elevated complexity and high
      mortality rates due to post-operative complications, is usually advocated for
      intestinal obstruction. This is the second issue reserved for the review of the
      ML-SIN concerning this topic, following that dedicated to definition, etiology,
      pathology and clinical characteristics. In this section, two expert colleagues
      complete the analysis of the different aspects of peritoneal sclerosis,
      discussing the therapy and the prevention of this serious complication of
      peritoneal dialysis.

PMID- 16001371
TI  - [Successful treatment with liposomal doxorubicin and foscarnet in a patient with
      widespread Kaposi's sarcoma and human herpes virus 8-related, serious
      hemophagocytic syndrome, after renal transplantation].
AB  - BACKGROUND: It is well known that the human herpes virus 8 (HHV8) is linked to
      several malignancies such as Kaposi's sarcoma (KS). Moreover, pancytopenia due to
      hemophagocytic syndrome could be associated with HHV8 infection. In renal
      transplant recipients affected by KS, the tapering of immunosuppression often
      leads to KS remission, but also results in graft loss in >50% of cases.
      Chemotherapy and antiviral therapy have also been used, mainly in the presence of
      visceral involvement. CASE REPORT: We describe a transplant recipient with
      widespread cutaneous and visceral KS HHV8 associated, complicated by
      hemophagocytic syndrome. At transplantation the patient's serology for HHV8 was
      negative, but thereafter it became positive. The first step in treatment
      (cyclosporine dose reduction until suspension) failed to improve the clinical
      course. Therefore, therapy combining liposomal doxorubicin and foscarnet was
      started. Clearance of HHV8 in the blood and complete resolution of the KS lesions
      were achieved. Immunosuppression with cyclosporine was resumed. No KS relapse has
      occurred, blood tests for HHV8 are negative, and graft function is good after a 5
      yr follow-up. CONCLUSIONS: Therapy combining liposomal doxorubicin and foscarnet
      was effective in this renal transplant recipient with KS and HHV8 infection and
      enabled us to resume immunosuppressive therapy; therefore, reducing the risk of
      acute/chronic rejection.

PMID- 16001372
TI  - Reflex epiphora in patients with dry eye symptoms: role of variable time Schirmer
      1 test.
AB  - PURPOSE: To report reflex epiphora in patients with dry eye symptoms and describe
      the role of variable time Schirmer-1 test. METHODS: The study was conducted in 16
      consecutive dry eye patients (32 eyes), nine male and seven female, aged 16 to 73
      years (mean 48.56-/+16.68 years), presenting with reflex epiphora. Each eye was
      subjected to Schirmer-1 test and the time elapsed in total wetting of the 35 mm
      strip from its placement into the conjunctiva was noted and test was graded. This
      was compared with symptomatology, closed chamber infrared thermometry, humidity,
      fluorescein tear break-up time (FTBUT), fluorescein stain test, and Lissamine
      green stain. RESULTS: Schirmer-1 test differentiated reflex epiphora in dry eye
      patients into groups 0 to 4 based on time it took to wet the 35 mm strip (Group 0
      = <=5 min; Group 1 = <=2 min; Group 2 = <=1.5 min; Group 3= <=1 min; Group 4 =
      <=1/2 min). The score was -0.04 in 8 eyes, -0.03 in 10 eyes, -0.02 in 2 eyes, 
      0.01 in 6 eyes, and 0.00 in 6 eyes in Groups 4, 3, 2, 1, and 0, respectively.
      Reflex epiphora had a statistically significant correlation to the symptomatology
      (p<0.001), lissamine green staining (p<0.001), closed chamber humidity difference
      (p<0.001), and FTBUT score (p=0.001). Fluorescein stain test and difference in
      infrared thermometry did not show any correlation. A statistically significant
      correlation existed between severe and mild to moderate reflex epiphora
      (p=0.002). However, the two groups separately failed to show any statistically
      significant relationship with the symptomatology (p=0.16), Lissamine green
      (p=0.69), humidity difference from close to open eye position (p=0.17), and FTBUT
      (p=0.25). Thermometry and fluorescein stain test showed no relationship.
      CONCLUSIONS: Schirmer-1 test with variable time quantifies reflex epiphora in dry
      eye patients, which was significantly related to the other tear function tests.

PMID- 16001374
TI  - Suspension made with amniotic membrane: clinical trial.
AB  - PURPOSE: To investigate if a suspension made with amniotic membrane could have a
      beneficial effect on ocular surface diseases. METHODS: In the Imola branch of the
      Eye Bank of Emilia Romagna, the authors prepared a suspension containing
      homogenized amniotic membrane previously conserved at -80 degrees Celsius.
      Subsequently, the authors gave this preparation to 21 patients: 8 had undergone
      lamellar keratoplasty, 4 had undergone penetrating keratoplasty, 2 had undergone
      photorefractive keratectomy with a delay of epithelialization, 3 had neurotrophic
      corneal ulcers, 2 had corneal burning, 1 had torpid corneal ulcer, and 1 had
      Sjogren syndrome. Each patient had been treated with conventional therapy for at
      least, 4 months without any clinical improvement. In this sample of eyes the
      authors evaluated the transparency and integrity of epithelium before and after
      the therapy by means of a fluorescein staining test, examining the area of
      epithelial defect as well as the phlogistic situation and the symptoms referred
      by patients. Nine eyes from this group of patients were studied by impression
      cytology before and after 3 months of use of suspension. The follow-up was 5
      months of once-weekly visits. RESULTS: In all patients, after 15 to 30 days the
      corneas became negative to fluorescein staining test and the epithelium seemed
      more complete and regular, there was an evident decrease of phlogistic situation
      in the conjunctiva, and an improvement of symptoms was referred by patients. The
      situation was stable during the whole follow-up. No side effects were noted. The
      impression cytology repeated 3 months after the treatment showed a significant
      corneal recovery of the cytologic situation with an important decrease of CK19+
      cells on the corneal surface. CONCLUSIONS: This new therapy, which is less
      traumatic than an implant of amniotic membrane, is safe, and can be repeated for
      a long period, could help patients with corneal superficial defects.

PMID- 16001373
TI  - Scanning laser polarimetry and retinal thickness analysis before and after laser
      in situ keratomileusis.
AB  - PURPOSE: To evaluate changes in retinal nerve fiber layer (RNFL) thickness after
      laser in situ keratomileusis (LASIK) using a scanning laser polarimeter with
      fixed corneal compensation (GDx) and the retinal thickness analyzer (RTA).
      METHODS: Thirty-eight eyes of 19 healthy subjects (10 female and 9 male; mean age
      37.0-/+8.8 years) underwent GDx and RTA measurements before and after LASIK. All
      subjects revealed mild to high myopia (mean spherical refraction: -4.0-/+2.75 D).
      Measurements using GDx were followed by RTA measurements after pupil dilation.
      All measurements were performed the day before LASIK and 1 week postoperatively.
      RESULTS: GDx revealed a decrease in nerve fiber layer thickness measurements
      after LASIK, but did not reach statistical significance (p>0.05). Using RTA, mean
      RNFL thickness (MRNFL) and RNFL cross sectional area decreased significantly
      after LASIK (p=0.03 and p=0.02, respectively). CONCLUSIONS: Scanning laser
      polarimetry revealed a slight decrease in RNFL thickness measurements after
      LASIK. MRNFL and RNFL cross section were significantly lower after LASIK using
      RTA. The changes might be artifacts in a small group of myopic subjects.

PMID- 16001375
TI  - Reconstruction of conjunctiva with amniotic membrane after excision of large
      conjunctival melanoma: a long-term study.
AB  - PURPOSE: To evaluate, on a long- term basis, the role of amniotic membrane in the
      reconstruction of large conjunctival defects after excision of large conjunctival
      melanoma. METHODS: Four consecutive patients with diffuse conjunctival melanoma
      involving both bulbar and palpebral conjunctiva were studied. Conjunctival
      melanoma was completely excised (with wide clinically disease-free margins) and
      amniotic membrane immediately sutured to the surrounding conjunctiva and sclera
      to cover the conjunctival defect. Minimum follow-up was 48 months. RESULTS:
      Successful conjunctival surface reconstruction and physiologic fornical depth
      were achieved in all patients within 6 weeks. No recurrence of primary melanoma
      was observed during long-term follow-up. CONCLUSIONS: Amniotic membrane
      transplantation is an effective alternative in ocular surface repairing surgery
      after removal of large conjunctival tumors.

PMID- 16001376
TI  - Implantation of iris devices in congenital and traumatic aniridias: surgery
      solutions and complications.
AB  - PURPOSE: To show surgical solutions in patients with traumatic and congenital
      aniridia, to evaluate the clinical improvement of these patients when iris
      prosthesis are implanted, and to examine safety and complications of these
      implants in a long-term follow-up. METHODS: Eight patients were included in this
      retrospective noncomparative case series. Nine eyes had an artificial iris
      implantation for traumatic or congenital aniridia. Three eyes received a black
      diaphragm intraocular lens (IOL) in capsular bag after phacoemulsification. An
      aniridia prosthesis, sulcus sutured, in front of a previous IOL was implanted in
      two eyes. A black diaphragm IOL, sulcus sutured, in two eyes; two iris diaphragm
      rings, in front of the previous IOL, in one eye; and a sector iris prosthesis in
      front of an IOL in the last eye were implanted. Mean follow-up was 22.5 months
      (range 16 to 44 months). RESULTS: All patients had improved visual acuity (VA)
      and visual comfort after surgery. The glare disability was subjectively better in
      all cases. Two patients developed new ocular hypertension after surgery; one of
      them was controlled by medical treatment and the other needed cyclodiode. Two of
      the patients with glaucoma preoperatively also needed cyclodiode procedure and
      one of them an Ahmed valve. CONCLUSIONS: Several kinds of artificial iris
      implants are available. In all our patients with aniridia, iris artificial
      prostheses improved VA and diminished visual discomfort. Glaucoma is the most
      important complication after artificial iris implant. It is possible to implant
      the iris prosthesis in the capsular bag, but this requires a large capsulorrhexis
      and presents a surgical challenge.

PMID- 16001377
TI  - Contrast and glare sensitivity after implantation of AcrySof and Human Optics 1CU
      intraocular lenses.
AB  - PURPOSE: To evaluate contrast and glare sensitivity of a newly developed,
      potentially accommodative intraocular lens. METHODS: The clinical interventional
      prospective randomized study included 20 patients (23 eyes) undergoing standard
      phacoemulsification with clear cornea incision in topical anesthesia. In the
      study group (10 eyes), the 1CU Human Optics intraocular lens (optics diameter 5.5
      mm) was implanted. The control group (13 eyes) received the monofocal AcrySof
      intraocular lens (optics diameter: 6.0 mm). Using a newly developed contrast
      measuring device, contrast and glare sensitivity were tested 4 weeks after
      surgery. RESULTS: The study group and control group did not vary significantly in
      contrast (p=0.38) or glare sensitivity (p=0.52). CONCLUSIONS: The results suggest
      that the newly developed 1CU Human Optics intraocular lens and the standard
      AcrySof intraocular lens do not vary significantly in glare and contrast
      sensitivity.

PMID- 16001378
TI  - Frequency of cataract surgery after intravitreal injection of high-dosage
      triamcinolone acetonide.
AB  - PURPOSE: To evaluate the frequency of cataract surgery after intravitreal
      injection of high-dosage triamcinolone acetonide in elderly patients. METHODS:
      This clinical interventional case series study included 144 phakic eyes that
      consecutively received an intravitreal injection of about 20 mg triamcinolone
      acetonide for diffuse diabetic macular edema (n=42 eyes), exudative age-related
      macular degeneration (n=98), and branch retinal vein occlusion (n=4). Mean age
      was 72.3-/+8.9 years. Mean follow-up was 11.0-/+6.8 months (median, 8.8 months;
      range, 3 to 35.5 months). Reinjections were carried out in 12 (8.3%) eyes.
      RESULTS: Cataract surgery was performed in 20 (13.9%) eyes 17.4-/+9.1 months
      (median, 12.7 months; range, 8.0 to 35.5 months) after the first intravitreal
      injection. Out of the 20 eyes undergoing cataract surgery, 19 (95%) eyes had
      received one intravitreal injection, and 1 (5%) eye had received two previous
      injections. CONCLUSIONS: In the elderly population of patients with exudative age
      related macular degeneration, diffuse diabetic macular edema, or branch retinal
      vein occlusion, intravitreal high-dosage injection of triamcinolone acetonide
      leads to clinically significant cataract with eventual cataract surgery in about
      15% to 20% of eyes within about 1 year after the intravitreal injection.

PMID- 16001379
TI  - Exchange technique for opacified hydrophilic acrylic intraocular lenses.
AB  - PURPOSE: To report an exchange technique for opacified hydrophilic acrylic
      intraocular lenses (IOLs). METHODS: . Twenty patients with two different types of
      opacified hydrophilic acrylic IOLs underwent IOL exchange by a single surgeon.
      Circumferential enlargement of the pre-existing capsulorrhexis was a critical
      step of the procedure, and resulted in expression of the IOL with minimal
      traction to the capsule. Implantation of an in-the-sulcus IOL followed. Surgical
      technique, complications, and visual outcome are discussed. RESULTS: Time from
      the initial cataract operation varied from 15 to 61 months (mean 30.5), and in
      all cases marked fibrosis was encountered. Eighteen patients had uncomplicated
      IOL exchange. Posterior capsule rupture occurred in two cases. Vision improved in
      16 cases, remained unchanged in 3 cases, and deteriorated in 1 case. CONCLUSIONS:
      IOL exchange of opacified hydrophilic acrylic IOLs is a particularly challenging
      procedure due to extensive fibrosis. Circumferential enlargement of the pre
      existing capsulorrhexis significantly facilitates the mobilization of the IOL
      from its fibrous pocket, with the use of minimal forces. Thus, the risk of
      zonular dehiscence or posterior capsule rupture is minimized.

PMID- 16001380
TI  - Discrimination between normal and early glaucomatous eyes with scanning laser
      polarimeter with fixed and variable corneal compensator settings.
AB  - PURPOSE: To evaluate the ability of scanning laser polarimetry (SLP) with a fixed
      corneal polarization compensator (GDx-FCC Nerve Fiber Analyzer) compared to one
      with a variable one (GDx-VCC) in the discrimination between healthy and early
      glaucomatous eyes. METHODS: Forty patients with early glaucomatous visual field
      defects, having a mean deviation of 3.1-/+1.6 dB and a pattern standard deviation
      of 3.1-/+0.9 dB, and 40 controls underwent both GDx-FCC and GDx-VCC. One eye per
      patient was considered. The cut-off point, taken as the value dividing healthy
      from glaucomatous eyes with highest probability, was determined for each GDx
      parameter. Linear discriminant functions (LDFs) were separately developed for GDx
      FCC and GDx-VCC parameters. Sensitivity, specificity, and area under the receiver
      operating characteristic curve (AROC) for discriminating between healthy and
      glaucomatous eyes were calculated for each GDx parameter, both according to the
      GDx normative database and after the selection of new cut-off points, and for the
      LDFs. RESULTS: All software-provided parameters showed low sensitivity and high
      specificity. The selection of new cut-off points improved the performance of all
      GDx parameters: VCC parameters performed better than FCC parameters; the largest
      AROCs were associated with the superior/nasal ratio for the GDx-FCC (0.86) and
      with the Number for the GDx-VCC (0.87). The LDFs provided an AROC of 0.89 with
      both the GDx-FCC and the GDx-VCC parameters. CONCLUSIONS: The GDx-VCC showed a
      higher ability in the early diagnosis of glaucoma when compared with the GDx-FCC.
      The individuation of the right cut-off point of selected parameters with both GDx
      settings performed better than the software-provided parameters, and comparably
      to the GDx parameters-based LDFs.

PMID- 16001381
TI  - Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as
      alternative to filtration surgery.
AB  - PURPOSE: To evaluate the efficacy and safety of bimatoprost 0.03% as an
      alternative to filtration surgery in patients with uncontrolled glaucoma. DESIGN:
      Interventional study. METHODS: A total of 83 consecutive patients (83 eyes)
      awaiting glaucoma surgery were enrolled in eight ophthalmic centers. Reasons for
      listing were inadequate intraocular pressure (IOP) control despite medical
      therapy and documented progression of visual field loss. All patients
      discontinued the previous treatment and were switched to bimatoprost 0.03% QD
      (one drop at 9 pm). The primary efficacy outcome was a 20% IOP reduction from
      baseline at each timepoint. IOP was measured at day 7, day 30, day 60, and day 90
      of treatment; less than 20% IOP reduction was considered as a failure. RESULTS:
      An IOP reduction of at least 20% was achieved in 74 patients (89.1%) after 7 days
      and in 64 patients (86.5%) after 30 days. Sixty-two patients (74.6%) maintained
      IOP readings 20% lower than baseline after 60 and 90 days. In these patients,
      visual field indices improved in 8 eyes (13%), and remained unchanged in 54 eyes
      (87%). Ocular side effects were conjunctival injection (15.6%), burning sensation
      (9.6%), foreign body sensation (4.8%), and eyelash growth (2.4%). CONCLUSIONS:
      This preliminary study shows that bimatoprost 0.03% could represent a useful
      therapeutic tool that might defer filtration surgery.

PMID- 16001382
TI  - Anecortave acetate for the treatment of subfoveal choroidal neovascularization
      secondary to age-related macular degeneration.
AB  - PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated
      clinically for treatment of exudative age-related macular degeneration (ARMD). A
      randomized, placebo-controlled, efficacy and safety dose duration study of
      anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient
      population was completed in June 2003. As part of this trial, 128 patients with
      subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and
      treated for up to 2 years by 18 clinical sites in the United States and European
      Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic
      examinations, general physical examinations, assessments of best-corrected logMAR
      visual acuity, and angiographic evaluations. The Digital Angiography Reading
      Center (New York City, NY) assessed lesion eligibility while the clinical
      investigators assessed overall patient eligibility prior to treatment. As part of
      this study, study medication was delivered as a posterior juxtascleral depot
      using a specially designed curved cannula at 6-month intervals if in the masked
      investigator's opinion the patient's lesion could benefit from additional
      treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study
      demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was
      statistically superior to placebo for stabilization of vision (<3 logMAR line
      change from baseline) and for inhibition of neovascular lesion growth. There were
      no serious treatment-related safety issues associated with either the study
      medication or the procedure for administration. CONCLUSIONS: Anecortave acetate
      15 mg for depot suspension is clinically efficacious compared to placebo for
      treatment of subfoveal exudative ARMD lesions when administered at 6-month
      intervals as a posterior juxtascleral depot.

PMID- 16001383
TI  - Reproducibility of optic nerve head measurements obtained by optical coherence
      tomography.
AB  - PURPOSE: To evaluate reproducibility of optic nerve head (ONH) morphometry
      measurements obtained by optical coherence tomography (the fast optical disk
      protocol of the -Zeiss model 3000 OCT system) in normal and glaucomatous eyes.
      METHODS: Prospective instrument-evaluation study. ONH measurements for 20 eyes
      were obtained in eight scan sessions taken during two visits to an ophthalmology
      clinic (10 normal patients, 10 glaucoma patients, one eye per subject). At every
      one of the eight sessions for each eye, estimates of eight ONH morphometry
      variables (see Main outcome measures) were obtained. The first two sessions were
      performed by two operators, followed by a 30-minute break. The same operators
      then completed a third and fourth session. This sequence was duplicated on a
      second visit. Intrasession, intersession, intervisit, and interoperator
      reproducibility of the eight variables were calculated by the use of a components
      variance model. Intraclass correlation coefficients (ICC) were used to assess
      reliability. RESULTS: Vertical integrated rim area, horizontal integrated rim
      area, disk area, cup area, rim area, cup/disk area ratio, cup/disk horizontal
      ratio, cup/disk vertical ratio. With the exception of the horizontal integrated
      rim area and rim area in normal subjects, the factor subject was the most
      important source of variance for all variables. Reliability values as measured by
      ICC for normal eyes were above 81%, with the exception of measurements of the
      horizontal integrated rim area (23.1%), rim area (33.3%), and disk area (64.7%).
      For glaucomatous eyes all values were above 85%, with the exception of the disk
      area (68.1%). CONCLUSIONS: ONH measurements obtained using the fast optical disk
      protocol of the Zeiss 3000 OCT system show good reproducibility, for both normal
      and glaucomatous eyes.

PMID- 16001385
TI  - Cerebrospinal fluid leakage during dacryocystorhinostomy in a patient with
      meningoencephalocele.
AB  - PURPOSE: To report a rare case of cerebrospinal fluid leakage during
      dacryocystorhinostomy in a patient with Mobius syndrome and meningoencephalocele
      and to explain our experience in the management of this complication. METHODS: A
      9-year-old girl with a history of surgically repaired fronto-ethmoidal
      meningoencephalocele and bilateral canthopexy was diagnosed with Mobius syndrome
      and underwent sequential bilateral dacryocystorhinostomy and silicone intubation
      because of dysgenesis of the lacrimal drainage pathway. RESULTS: Both
      dacryocystorhinostomies resulted in cerebrospinal fluid leakage, which
      spontaneously ceased with conservative management. CONCLUSIONS:
      Dacryocystorhinostomy surgery in patients with a history of trauma or surgery or
      congenital defects around the base of the nose or lacrimal system may rarely
      result in cerebrospinal fluid leakage; thus an ophthalmologist should be familiar
      with its management.

PMID- 16001384
TI  - Implantation of stimulation electrodes in the subretinal space to demonstrate
      cortical responses in Yucatan minipig in the course of visual prosthesis
      development.
AB  - PURPOSE: During the course of the development of visual prostheses, subretinal
      stimulation films were implanted in micropigs in order to prove the feasibility
      of subretinal electrical stimulation with subsequent cortical response. One aim
      was to demonstrate that epidural recording of visual evoked potentials is
      possible in the micropig. METHODS: Film-bound stimulation electrode arrays were
      placed in the subretinal space of micropigs. This enabled the retina to be
      stimulated subretinally. Since conventional visual evoked potential (VEP)
      measuring is virtually impossible in the pig from the neurosurgical point of
      view, epidural recording electrode arrays were positioned over the visual cortex
      as permanent electrodes. RESULTS: The feasibility of temporary implantation of
      film-bound stimulation electrode arrays was successfully demonstrated in the
      micropig model. On stimulation with monopolar voltage pulses (1000 to 3000 mV),
      reproducible epidural VEP measurements (5 to 10 micronV) were detected.
      CONCLUSIONS: The feasibility of subretinal stimulation of the retina was
      demonstrated in a retinal model that is similar to the human retina. This animal
      model therefore offers a suitable means of studying the tolerability of
      stimulation situations in the course of visual prosthesis development.

PMID- 16001386
TI  - Iatrogenic Horner's syndrome.
AB  - PURPOSE: To report two cases of Horner's syndrome. One presented after the
      ablation of a schwannoma of the cervical sympathetic chain, the second after
      upper thorascopic sympathectomy for primary palmar hyperhidrosis. METHODS: A 42
      year-old man underwent excision of a left neck mass found during routine physical
      examination. A 20-year-old girl with axillary and palmar hyperhidrosis was
      treated with cervical sympathectomy. RESULTS: In the early postoperative days,
      miosis, ptosis, anhidrosis, and enophthalmos were observed. CONCLUSIONS: In the
      ablation of a schwannoma, postoperative Horner's syndrome is associated with the
      relationship between nerves and the tumor mass, which makes it impossible to
      separate them surgically in most cases. In thorascopic sympathectomy, patients
      should be warned of this complication.

PMID- 16001387
TI  - Spontaneous fracture of an implanted posterior chamber intraocular lens.
AB  - PURPOSE: Spontaneous fracture of an intraocular lens (IOL) haptic is a rare
      complication of cataract surgery. The authors report a case of spontaneous
      fracture of an implanted posterior chamber IOL. CASE: Five years ago, a 12-year
      old patient underwent linear lens extraction, posterior capsulotomy, and anterior
      vitrectomy due to traumatic cataract and received a polymethyl methacrylate
      (PMMA) biconvex posterior chamber IOL implanted in ciliary sulcus. Five years
      later, IOL optic was found in anterior chamber with its haptics broken from the
      optic-haptic junction. DISCUSSION: The broken haptic was examined with scanning
      electron microscopy. The fracture site of the haptic was on the optic-haptic
      junction. The fractured surface had a regular appearance. CONCLUSIONS: To our
      knowledge, this is the fourth report of spontaneous fracture of an implanted
      posterior chamber IOL.

PMID- 16001388
TI  - Immune recovery uveitis in an iatrogenically immunosuppressed patient.
AB  - PURPOSE: To report a case of immune recovery uveitis (IRU) in an iatrogenically
      immunosuppressed human immunodeficiency virus (HIV)-negative patient. METHODS:
      Interventional case report. One patient was diagnosed with cytomegalovirus
      retinitis in the left eye while receiving immunosuppressive treatment following
      renal transplantation. The retinitis resolved completely with systemic
      ganciclovir. Further reduction of immunosuppressive treatment, causing a rapid
      increase in CD4-T lymphocyte count, was associated in the same eye with the
      occurrence of IRU consisting of anterior uveitis, vitritis, and macular edema.
      RESULTS: Visual acuity at IRU presentation onset was 20/200 in the left eye.
      After 6 weeks of follow-up, the uveitis resolved with topical and periocular
      steroid treatment. Visual acuity restored to 20/40. CONCLUSIONS: IRU can occur in
      iatrogenically immunosuppressed HIV-negative patients.

PMID- 16001389
TI  - Combined surgical ablation and intravitreal triamcinolone acetonide for retinal
      angiomatous proliferation.
AB  - PURPOSE: Neovascular age-related macular degeneration (ARMD) with retinal
      angiomatous proliferation (RAP) has a poor natural history and the efficacy of
      any treatment has not yet been established. The authors describe a combined
      surgical treatment. METHODS: A 76-year-old woman presented with a best-corrected
      visual acuity (BCVA) of 20/600 in the right eye and macula with stage 3 RAP as
      identified by fluorescein angiography (FA), indocyanine green angiography (ICGA),
      and optical coherence tomography (OCT). After a standard three-port pars plana
      core vitrectomy (PPV), endodiathermy of the arteriolar and venous feeder vessels
      of each lesion was performed, intraretinal RAP feeder vessels were cut with
      manual vertical intraocular scissors, and 0.1 mL of triamcinolone acetonide
      (TAAC) was injected intravitreally. At 1 and 4 weeks and at the sixth month, the
      patient underwent a complete eye examination, FA, ICGA, and OCT to assess
      outcomes and complications. RESULTS: Six months later, BCVA was stable at 20/300,
      intraocular pressure was 15 mmHg, anterior segment and vitreous cavity were clear
      without evidence of TAAC granules, and retina was attached. FA and ICGA showed a
      complete occlusion of the RAP and absence of leakage or ischemia and OCT
      demonstrated decreased macular thickness with resolution of both intraretinal
      edema and pigment epithelium detachment, and the restoration of the normal
      macular profile. At the end of follow-up, the authors did not observe any ocular
      or systemic complication. CONCLUSIONS: Surgical approach to RAP stage 3 with
      intravitreal injection of 4 mg of TAAC was safe and anatomically effective.

PMID- 16001390
TI  - Highly diastereoselective Diels-Alder reactions with enantiopure sulfinyl
      substituted 1-hydroxymethyldienes.
AB  - Enantiopure hydroxy-2- and -3-sulfinyldienes undergo highly selective Diels-Alder
      cycloadditions with various dienophiles controlled by the chiral sulfur atom. The
      related hydroxy-2-sulfonyldienes display complementary pi-facial selectivity.

PMID- 16001391
TI  - Functional transfer of eukaryotic expression plasmids to mammalian cells by
      Listeria monocytogenes: a mechanistic approach.
AB  - BACKGROUND: Cystic fibrosis (CF) is one of the most common monogenic disorders in
      the caucasian population. Gene therapy for CF is principally feasible and
      bacterial transfer systems might provide novel possibilities for therapy.
      However, transfection efficiencies are low and need to be improved. Thus, more
      detailed understanding of the DNA transfer mechanism is necessary to
      systematically eliminate these restrictions. METHODS: Functional transfer of GFP
      CFTR (cystic fibrosis transmembrane conductance regulator) to eukaryotic cells
      using attenuated Listeria monocytogenes mediated gene transfer (bacteriofection)
      was shown by fluorescent microscopy, flow cytometry, immunoblotting and whole
      cell patch clamping. The characteristics of plasmid transfer were studied by use
      of electron and fluorescence microscopy, flow cytometry and Southern blotting.
      Polymerase chain reaction (PCR) was used to screen the genome of bacteriofected
      cells for cotransfer of chromosomal bacterial DNA. RESULTS: Correct intracellular
      localization and functionality of the GFP-CFTR fusion protein after
      bacteriofection was shown. Efficient bacterial lysis and release of bacterial
      content was demonstrated using antibiotics to kill intracellular bacteria.
      Although only low transfection rates were observed, high numbers of transferred
      plasmids were detected in host cells under these conditions. However, they were
      associated with high molecular weight entities and not available to cytosolic
      transcription. Cotransfer of bacterial genomic DNA was observed in transfectants
      but occurred at low frequencies. CONCLUSIONS: In this work we demonstrate that
      low rates of bacteria-mediated transfection are not due to poor invasion of
      bacteria, insufficient bacterial lysis, or plasmid DNA degradation. Our data
      suggest that the transferred plasmid DNA is associated with higher macromolecular
      structures inhibiting nuclear transport and transgene transcription.

PMID- 16001393
TI  - Degradation and drug release of phosphate glass/polycaprolactone biological
      composites for hard-tissue regeneration.
AB  - Phosphate-based glass (P-glass) and poly(epsilon-caprolactone) (PCL) composites
      were fabricated in a sheet form by solvent extraction and thermal pressing
      methods, and the antibiotic drug Vancomycin was loaded within the composites for
      use as a hard-tissue regenerative. The degradation and drug-release rate of the
      composites in vitro were tailored by modifying the glass composition: 0.45
      P(2)O(5)-x CaO-(0.55-x)Na(2)O, where x=0.2, 0.3, 0.4, and 0.5. Compared to pure
      PCL, all the P-glass/PCL composites degraded to a higher degree, and the
      composite with lower-CaO glass showed a higher material loss. This was attributed
      mainly to the dissolution of the glass component. The glass dissolution also
      increased the degradation of PCL component in the composites. The Vancomycin
      release from the composites was strongly dependent on the glass composition. Drug
      release in pure PCL was initially abrupt and flattened out over a prolonged
      period. However, glass/PCL composites (particularly in the glass containing
      higher-CaO) exhibited a reduced initial burst and a higher release rate later.
      Preliminary cell tests on the extracts from the glass/PCL composites showed
      favorable cell proliferation, but the level was dependent on the ionic
      concentration of the extracts. The cell proliferation on the diluted extracts
      from the composite with higher-CaO glass was significantly higher than that on
      the blank culture dish. These observations confirmed that the P-glass/PCL
      composites are potentially applicable for use as hard-tissue regeneration and
      wound-healing materials because of their controlled degradation and drug-release
      profile as well as enhanced cell viability.

PMID- 16001392
TI  - Inhibition by TNF-alpha and IL-4 of cationic lipid mediated gene transfer in
      cystic fibrosis tracheal gland cells.
AB  - BACKGROUND: In vivo, tracheal gland serous cells highly express the cystic
      fibrosis transmembrane conductance regulator (cftr) gene. This gene is mutated in
      the lethal monogenic disease cystic fibrosis (CF). Clinical trials in which the
      human CFTR cDNA was delivered to the respiratory epithelia of CF patients have
      resulted in weak and transient gene expression. METHODS AND RESULTS: As CF is
      characterized by mucus inspissation, airway infection, and severe inflammation,
      we tested the hypothesis that inflammation and especially two cytokines involved
      in the Th1/Th2 inflammatory response, interleukin 4 (IL-4) and TNFalpha, could
      inhibit gene transfer efficiency using a model of human CF tracheal gland cells
      (CF-KM4) and Lipofectamine reagent as a transfection reagent. The specific
      secretory defects of CF-KM4 cells were corrected by Lipofectamine-mediated human
      CFTR gene transfer. However, this was altered when cells were pre-treated with IL
      4 and TNFalpha. Inhibition of luciferase reporter gene expression by IL-4 and
      TNFalpha pre-treated CF-KM4 cells was measured by activity and real-time RT-PCR.
      Both cytokines induced similar and synergistic inhibition of transgene expression
      and activity. This cytokine-mediated inhibition could be prevented by anti
      inflammatory agents such as glucocorticoids but not by non-steroidal (NSAI)
      agents. CONCLUSIONS: This data suggests that an inflammatory context generated by
      IL-4 and TNFalpha can inhibit human CFTR gene transfer in CF tracheal gland cells
      and that glucocorticoids may have a protecting action.

PMID- 16001394
TI  - Hyaluronic acid hydrogel added with ibuprofen-lysine for the local treatment of
      chondral lesions in the knee: in vitro and in vivo investigations.
AB  - The effect of hyaluronan-based hydrogel with a cross-linking degree of 50% (i.e.,
      the amount of carboxylate groups involved in the cross-lining reaction) (Hyal
      50%), loaded with an anti-inflammatory drug (ibuprofen-lysine) for local
      administration in the osteoarthritic knee was evaluated. The kinetic of drug
      release from Hyal 50% hydrogel was performed in vitro by a continuous flow
      system. The release was studied at three different rates (0.375, 0.073, and 0.005
      mL/s), and for the slowest one a period of 8 days was necessary to receive the
      complete release of the drug. A chondral defect was caused in the right femoral
      medial condyle of 24 rabbits. Twelve animals were treated with Hyal 50%+ibuprofen
      lysine and 12 with Hyal 50% by percutaneous injection. The treatments were
      repeated every 10 days, for three or five times. At 30 and 50 days, no
      significant differences were observed between the groups (mean score at 30 days:
      4.4+/-0.6 in Hyal 50%-treated group and 5.1+/-0.7 in Hyal 50% +Ibuprofen-lysine
      treated group; mean score at 50 days: 6.9+/-0.6 in Hyal 50%-treated group and
      7.1+/-0.6 in Hyal 50%+ Ibuprofen-lysine-treated group). A significant difference
      was observed in bone mineral density of the total tibia of rabbits treated by
      Hyal 50% + Ibuprofen-lysine in comparison with those treated only by Hyal 50%.
      The positive effects of Hyal 50% on chondral lesions were maintained in the
      presence of ibuprofen-lysine with the adjunctive effect of an increased limb
      usage, most likely due to less pain and discomfort.

PMID- 16001395
TI  - Strength retention of 70:30 poly(L-lactide-co-D,L-lactide) following real-time
      aging.
AB  - This study evaluated the in vitro strength retention and polymer characteristics
      of plates and screws made from commercially available 70:30 poly(L-lactide-co-D,L
      lactide) over a 2-year time period. Test samples included three routine
      manufacturing lots each of plates (1.2 mm thick, 41.70 mm long, with 2.5-mm
      holes), which were machined from compression-molded sheets, and screws (2.4-mm
      major diameter and 1.86-mm minor diameter), which were manufactured by injection
      molding. All samples were sterilized by e-beam irradiation prior to in vitro
      aging following a standard methodology. Mechanical testing and polymer analysis
      was performed after 0, 6, 13, 26, 39, 52, 65, 78, and 104 weeks. The initial
      (time zero) tensile strength of the plates averaged 33.2+/-1.9 MPa; the plates
      retained 100% of this strength at 6 weeks, 84% at 13 weeks, and 34% at 39 weeks.
      The screws had an initial (time zero) shear strength of 29.8+/-4.2 MPa, and
      maintained 97% of this strength at 26 weeks and 73% of this strength at 39 weeks.
      The inherent viscosity and molecular weight (M(w)) at time zero averaged
      approximately 1.4 dL/g and 165,000 g/mol, respectively, and decreased at similar
      rates for both the plates and screws. These results demonstrate excellent
      strength retention of devices fabricated from 70:30 poly(L-lactide-co-D,L
      lactide) over time periods exceeding those associated with normal bone healing.

PMID- 16001396
TI  - Theoretical study of volume changes associated with the helix-coil transition of
      an alanine-rich peptide in aqueous solution.
AB  - The changes in the partial molar volume (PMV) associated with the conformational
      transition of an alanine-rich peptide AK16 from the alpha-helix structure to
      various random coil structures are calculated by the three-dimensional
      interaction site model (3D-RISM) theory coupled with the Kirkwood-Buff theory.
      The volume change is analyzed by decomposing it into contributions from geometry
      and hydration: the changes in the van der Waals, void, thermal, and interaction
      volume. The total change in the PMV is positive. This is primarily due to the
      growth of void space within the peptide, which is canceled in part by the volume
      reduction resulting from the increase in the electrostatic interaction between
      the peptide and water molecules. The changes in the void and thermal volume of
      the coil structures are widely distributed and tend to compensate each other.
      Additionally, the relations between the hydration volume components and the
      surface properties are investigated. We categorize coil structures into extended
      coils with the PMV smaller than helix and general coils with the PMV larger than
      helix. The pressure therefore can both stabilize and destabilize the coil
      structures. The latter seems to be a more proper model of random coil structures
      of the peptide.

PMID- 16001397
TI  - Detection of the centriole tyr- or acet-tubulin changes in endothelial cells
      treated with thrombin using microscopic immunocytochemistry.
AB  - We used electron microscopic immunocytochemistry to examine the pattern of
      centriolar staining for tyrosinated or acetylated alpha-tubulin in endothelial
      cells during short-term incubation with thrombin. Endothelial cells isolated from
      human aorta (HAEC) and those isolated from umbilical vein (HUVEC) displayed an
      increase in the intensity of centriolar staining for acet-tubulin within 1 min
      after thrombin addition. A decrease in the intensity of centriolar staining for
      tyr-tubulin was detected in HUVEC within 1 min after thrombin addition, while in
      HAEC centriolar staining for tyr-tubulin became less intense only 5 min later.
      Mother and daughter centrioles of HUVEC cells displayed different intensity of
      immunostaining for acet-tubulin and showed no significant variation in the number
      of subdistal appendages after thrombin addition. Differently, HAEC cells had the
      same staining pattern of mother and daughter centrioles in both thrombin
      untreated and thrombin-treated cultures. A sharp increase in the number of
      subdistal appendages of mother centriole occurred in HAEC within 5 min of
      incubation with thrombin. Our findings provided the direct evidence for
      centrosome involvement in the ligand-mediated signaling events and showed for the
      first time that ligand-dependent centrosome reorganization includes the centriole
      per se. Furthermore, based on our observations we would like to propose that MT
      nucleating/anchoring properties of the centrosome are subject to rapid regulation
      by external signals such as thrombin.

PMID- 16001398
TI  - The unconventional myosin-VIIa associates with lysosomes.
AB  - Mutations in the myosin-VIIa (MYO7a) gene cause human Usher disease,
      characterized by hearing impairment and progressive retinal degeneration. In the
      retina, myosin-VIIa is highly expressed in the retinal pigment epithelium, where
      it plays a role in the positioning of melanosomes and other digestion organelles.
      Using a human cultured retinal pigmented epithelia cell line, ARPE-19, as a model
      system, we have found that a population of myosin-VIIa is associated with
      cathepsin D- and Rab7-positive lysosomes. Association of myosin-VIIa with
      lysosomes was Rab7 independent, as dominant negative and dominant active versions
      of Rab7 did not disrupt myosin-VIIa recruitment to lysosomes. Association of
      myosin-VIIa with lysosomes was also independent of the actin and microtubule
      cytoskeleton. Myosin-VIIa copurified with lysosomes on density gradients, and
      fractionation and extraction experiments suggested that it was tightly associated
      with the lysosome surface. These studies suggest that myosin-VIIa is a lysosome
      motor.

PMID- 16001400
TI  - Fold usage on genomes and protein fold evolution.
AB  - We review fold usage on completed genomes to explore protein structure evolution.
      The patterns of presence or absence of folds on genomes gives us insights into
      the relationships between folds, the age of different folds and how we have
      arrived at the set of folds we see today. We examine the relationships between
      different measures which describe protein fold usage, such as the number of
      copies of a fold per genome, the number of families per fold, and the number of
      genomes a fold occurs on. We obtained these measures of fold usage by searching
      for the structural domains on 157 completed genome sequences from all three
      kingdoms of life. In our comparisons of these measures we found that bacteria
      have relatively more distinct folds on their genomes than archaea. Eukaryotes
      were found to have many more copies of a fold on their genomes. If we separate
      out the different fold classes, the alpha/beta class has relatively fewer
      distinct folds on large genomes, more copies of a fold on bacteria and more folds
      occurring in all three kingdoms simultaneously. These results possibly indicate
      that most alpha/beta folds originated earlier than other folds. The expected
      power law distribution is observed for copies of a fold per genome and we found a
      similar distribution for the number of families per fold. However, a more
      complicated distribution appears for fold occurrence across genomes, which
      strongly depends on fold class and kingdom. We also show that there is not a
      clear relationship between the three measures of fold usage. A fold which occurs
      on many genomes does not necessarily have many copies on each genome. Similarly,
      folds with many copies do not necessarily have many families or vice versa.

PMID- 16001399
TI  - Antisense oligonucleotide reduction of DGAT2 expression improves hepatic
      steatosis and hyperlipidemia in obese mice.
AB  - In this study, we investigated the role of acyl-coenzyme A:diacylglycerol
      acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by
      reducing its expression in liver and fat with an optimized antisense
      oligonucleotide (ASO). High-fat diet-induced obese (DIO) C57BL/6J mice and ob/ob
      mice were treated with DGAT2 ASO, control ASO, or saline. DGAT2 ASO treatment
      reduced DGAT2 messenger RNA (mRNA) levels by more than 75% in both liver and fat
      but did not change DGAT1 mRNA levels in either of these tissues, which resulted
      in decreased DGAT activity in liver but not in fat. DGAT2 ASO treatment did not
      cause significant changes in body weight, adiposity, metabolic rate, insulin
      sensitivity, or skin microstructure. However, DGAT2 ASO treatment caused a marked
      reduction in hepatic triglyceride content and improved hepatic steatosis in both
      models, which was consistent with a dramatic decrease in triglyceride synthesis
      and an increase in fatty acid oxidation observed in primary mouse hepatocytes
      treated with DGAT2 ASO. In addition, the treatment lowered hepatic triglyceride
      secretion rate and plasma triglyceride levels, and improved plasma lipoprotein
      profile in DIO mice. The positive effects of the DGAT2 ASO were accompanied by a
      reduction in the mRNA levels of several hepatic lipogenic genes, including SCD1,
      FAS, ACC1, ACC2, ATP-citrate lyase, glycerol kinase, and HMG-CoA reductase. In
      conclusion, reduction of DGAT2 expression in obese animals can reduce hepatic
      lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby
      leading to an improvement in metabolic syndrome.

PMID- 16001401
TI  - Quantitative measurements of alternating finger tapping in Parkinson's disease
      correlate with UPDRS motor disability and reveal the improvement in fine motor
      control from medication and deep brain stimulation.
AB  - The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome
      measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each
      subscore of the motor section (UPDRS III) compresses a wide range of motor
      performance into a coarse-grained scale from 0 to 4; the assessment of
      performance can also be subjective. Quantitative digitography (QDG) is an
      objective, quantitative assessment of digital motor control using a computer
      interfaced musical keyboard. In this study, we show that the kinematics of a
      repetitive alternating finger-tapping (RAFT) task using QDG correlate with the
      UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients
      with PD. We show that dopaminergic medication and an average of 9.5 months of
      bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) significantly
      improve UPDRS and QDG scores but may have different effects on certain kinematic
      parameters. This study substantiates the use of QDG to measure motor outcome in
      trials of PD therapeutics and shows that medication and B-STN DBS both improve
      fine motor control.

PMID- 16001402
TI  - Possible anticipation in BAFME: three generations examined in a Japanese family.

PMID- 16001403
TI  - Large-scale prediction of function shift in protein families with a focus on
      enzymatic function.
AB  - Protein function shift can be predicted from sequence comparisons, either using
      positive selection signals or evolutionary rate estimation. None of the methods
      have been validated on large datasets, however. Here we investigate existing and
      novel methods for protein function shift prediction, and benchmark the accuracy
      against a large dataset of proteins with known enzymatic functions. Function
      change was predicted between subfamilies by identifying two kinds of sites in a
      multiple sequence alignment: Conservation-Shifting Sites (CSS), which are
      conserved in two subfamilies using two different amino acid types, and Rate
      Shifting Sites (RSS), which have different evolutionary rates in two subfamilies.
      CSS were predicted by a new entropy-based method, and RSS using the Rate-Shift
      program. In principle, the more CSS and RSS between two subfamilies, the more
      likely a function shift between them. A test dataset was built by extracting
      subfamilies from Pfam with different EC numbers that belong to the same domain
      family. Subfamilies were generated automatically using a phylogenetic tree-based
      program, BETE. The dataset comprised 997 subfamily pairs with four or more
      members per subfamily. We observed a significant increase in CSS and RSS for
      subfamily comparisons with different EC numbers compared to cases with same EC
      numbers. The discrimination was better using RSS than CSS, and was more
      pronounced for larger families. Combining RSS and CSS by discriminant analysis
      improved classification accuracy to 71%. The method was applied to the Pfam
      database and the results are available at http://FunShift.cgb.ki.se. A closer
      examination of some superfamily comparisons showed that single EC numbers
      sometimes embody distinct functional classes. Hence, the measured accuracy of
      function shift is underestimated.

PMID- 16001404
TI  - Design of combinatorial protein libraries of optimal size.
AB  - In this article we introduce a computational procedure, OPTCOMB (Optimal Pattern
      of Tiling for COMBinatorial library design), for designing protein hybrid
      libraries that optimally balance library size with quality. The proposed
      procedure is directly applicable to oligonucleotide ligation-based protocols such
      as GeneReassembly, DHR, SISDC, and many more. Given a set of parental sequences
      and the size ranges of the parental sequence fragments, OPTCOMB determines the
      optimal junction points (i.e., crossover positions) and the fragment contributing
      parental sequences at each one of the junction points. By rationally selecting
      the junction points and the contributing parental sequences, the number of
      clashes (i.e., unfavorable interactions) in the library is systematically
      minimized with the aim of improving the overall library quality. Using OPTCOMB,
      hybrid libraries containing fragments from three different dihydrofolate
      reductase sequences (Escherichia coli, Bacillus subtilis, and Lactobacillus
      casei) are computationally designed. Notably, we find that there exists an
      optimal library size when both the number of clashes between the fragments
      composing the library and the average number of clashes per hybrid in the library
      are minimized. Results reveal that the best library designs typically involve
      complex tiling patterns of parental segments of unequal size hard to infer
      without relying on computational means.

PMID- 16001405
TI  - Crystal structure of an Apo mRNA decapping enzyme (DcpS) from Mouse at 1.83 A
      resolution.

PMID- 16001406
TI  - Transcultural comparison of psychogenic movement disorders.
AB  - Prompted by the lack of cross-cultural comparative data, and because a better
      understanding in the different clinical presentations of psychogenic movement
      disorders (PMDs) is relevant to neurological assessment and interventions, we
      compared the phenomenology, anatomical distribution, and functional impairment of
      PMDs in the United States and Spain. Consecutive patients diagnosed with PMD by a
      movement disorder specialist from one US site and from eight Spanish university
      centers were included in the study. The two groups were similar in their movement
      types, anatomical distribution, and functional impairment. PMDs were more
      prevalent in women than in men and were most common in upper and lower
      extremities. Gait and speech dysfunctions were distributed similarly in both
      countries. We found action tremor to be the most frequent PMD in both countries.

PMID- 16001407
TI  - Essential tremor centralized brain repository: diagnostic validity and clinical
      characteristics of a highly selected group of essential tremor cases.
AB  - We studied essential tremor (ET) cases enrolled in the Essential Tremor
      Centralized Brain Repository to (1) assess the validity of their diagnoses and
      (2) characterize the clinical features in a group of highly selected cases who
      might reflect a far end of the disease spectrum. Our over-arching goal was to
      provide a perspective of ET that complements that derived from population-based
      and clinic-based studies. Based on a history and videotaped examination, 94 of
      100 ET cases had their diagnoses confirmed; most of the remainder had Parkinson's
      disease. When compared with ET cases ascertained through populations and clinics,
      a large proportion had been prescribed medication for tremor (87.2%), had a
      family history of tremor (88.3%), had rest tremor (33.0%), or had neck tremor
      (60.6%). One patient had facial tremor, which has not been reported previously.
      As has been reported once before, a large proportion wore hearing aids (26.9% of
      the 67 participants age>or=70). In summary, diagnostic validity was high. In
      terms of their clinical characteristics, the high proportion of cases with severe
      tremor and varied disease manifestations (neck tremor, rest tremor) make these
      cases a valuable resource in pathological studies; the high proportion with
      familial tremor would provide an enriched sample for genetic studies.

PMID- 16001408
TI  - Throat clicking as the initial symptom of Parkinson's disease.
AB  - The presenting manifestations of Parkinson's disease (PD) are variable, but a
      majority of patients note tremor as the initial symptom. Others complain of
      slowing of movements, loss of dexterity, fatigue, or changes in handwriting as
      initial symptoms. We describe a patient who developed an unusual clicking sound
      emanating from his throat as the initial manifestation of PD.

PMID- 16001409
TI  - Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in
      PARK2.
AB  - We performed [123I] MIBG myocardial scintigraphy in two of three patients with
      PARK2 from unrelated families and examined the heart tissues from the three
      patients immunohistochemically using an antibody against tyrosine hydroxylase
      (TH) to see whether cardiac sympathetic nerve is involved. Cardiac uptake of MIBG
      was normal except for a slight decrease in the late phase in one of the patients.
      Postmortem examination revealed that TH-immunoreactive nerve fibers in the
      epicardium were well preserved in all three patients. The present study confirmed
      that cardiac sympathetic nerve is well preserved in PARK2 with a homozygous exon
      deletion, which accounts for normal cardiac uptake of MIBG. Moreover, normal
      cardiac uptake of MIBG might be of potential diagnostic value to indicate the
      absence of Lewy body pathology, even in patients with levodopa-responsive
      Parkinsonism, as in PARK2.

PMID- 16001410
TI  - Defining the breakpoints of the quaking(viable) mouse mutation reveals a
      duplication from a Parkin intron.
AB  - The quakingviable (qkv) mutant mouse shows a recessive neurological phenotype
      that includes central nervous system (CNS) dysmyelination, seizures, and tremor
      associated with voluntary movement. The molecular defect of qkv has been
      previously reported to be a spontaneous approximately 1 megabase (Mb) deletion in
      the proximal region of mouse chromosome 17 that occurred in the DBA mouse strain
      more than four decades ago. The mutation has recently been shown to affect three
      genes in the region: Quaking (qk), Parkin-coregulated gene (Pacrg), and Parkin.
      Here we determine the exact deletion breakpoints and demonstrate that the
      mutation is not just comprised of a approximately 1.1 Mb deletion, but also
      harbors a small 163 bp duplication fragment between the deletion breakpoints.
      Although the distal deletion breakpoint is within the fifth intron of the mouse
      Parkin gene, the duplicated sequence is derived from the sixth Parkin intron and
      shows positive transcriptional activity on a reporter gene in vitro. This
      complexity provides insight into a well-studied neurological mutant and may have
      a role in affecting the phenotype observed.

PMID- 16001411
TI  - Abnormal sleep architecture is an early feature in the E46K familial
      synucleinopathy.
AB  - We examined 7 patients from a family harboring a novel mutation in the alpha
      synuclein gene (E46K) that segregated with a phenotype of parkinsonism and
      dementia with Lewy bodies. An abnormal restless sleep was the presenting symptom
      in 2 of them. Polysomnographic (PSG) studies were performed in 4 of the 7
      patients and in 2 asymptomatic carriers of the mutation. A severe loss of both
      rapid eye movement (REM) and non-REM sleep was observed in 2 patients complaining
      of insomnia and in a third parkinsonian member of the family who did not complain
      of trouble with sleeping. Another parkinsonian family member had a mild
      disorganization of the sleep architecture. The 2 asymptomatic carriers also had
      minor changes in the PSG findings. Episodes of bizarre behavior at night were
      reported historically in the 2 symptomatic patients, but we did not observed the
      behaviors during the PSG studies. REM sleep behavior disorder could not be
      recorded in any case. Our findings expand the spectrum of sleep disorders
      reported in synucleinopathies whether sporadic or familial.

PMID- 16001412
TI  - Neuroleptic-induced acute laryngeal dystonia causing stridor: a lesson to
      remember.

PMID- 16001413
TI  - Escaping Parkinson's disease: a neurologically healthy octogenarian with the
      LRRK2 G2019S mutation.

PMID- 16001414
TI  - No going home for hospitalized Huntington's disease patients.
AB  - Little is known as to what happens to people with Huntington's disease (HD) at
      the end of life. Exploratory analysis was performed for all admissions of people
      with HD in the Nationwide Inpatient Sample database, a 20% stratified sample of
      all US hospitalizations, from 1996 to 2002. Using the principal diagnosis and
      procedure, admission cohorts were determined. The common HD-associated reasons
      for admission were pneumonia (including aspiration, 22%), psychiatric (21.5%),
      debilitation (hypovolemia, nutritional deficiencies, and decubitus ulcers,
      15.5%), trauma (5.7%), and nonpulmonary infections (urinary tract infections and
      sepsis, 11.%). Twenty-two percent were admitted for medical problems unrelated to
      HD. Emergency departments were the most frequent source of admission (60%), most
      had Medicare or Medicaid as the expected payer (80.6%), 54.4% of all admissions
      were discharged to long-term care facilities (LTCFs), and 3.7% died. The highest
      mortality was seen in the pneumonia (7.68%) and sepsis (7.39%) cohorts. Of the
      elective admissions, between 49.71% and 60.31% were discharged to LTCFs,
      representing new LTCF admissions. Based on this exploratory analysis,
      hospitalized HD patients are admitted late in the course of their illness, are
      severely disabled, and are commonly discharged to LTCFs. With 60.31% of the
      discharges representing new LTCF admissions, this finding shows that there is no
      going home from the hospital for people with HD.

PMID- 16001415
TI  - Pregnancy in Parkinson's disease: unique case report and review of the
      literature.

PMID- 16001416
TI  - Modeling protein recognition of carbohydrates.
AB  - We have a limited understanding of the details of molecular recognition of
      carbohydrates by proteins, which is critical to a multitude of biological
      processes. Furthermore, carbohydrate-modifying proteins such as glycosyl
      hydrolases and phosphorylases are of growing importance as potential drug
      targets. Interactions between proteins and carbohydrates have complex
      thermodynamics, and in general the specific positioning of only a few hydroxyl
      groups determines their binding affinities. A thorough understanding of both
      carbohydrate and protein structures is thus essential to predict these
      interactions. An atomic-level view of carbohydrate recognition through structures
      of carbohydrate-active enzymes complexed with transition-state inhibitors reveals
      some of the distinctive molecular features unique to protein-carbohydrate
      complexes. However, the inherent flexibility of carbohydrates and their often
      water-mediated hydrogen bonding to proteins makes simulation of their complexes
      difficult. Nonetheless, recent developments such as the parameterization of
      specific force fields and docking scoring functions have greatly improved our
      ability to predict protein-carbohydrate interactions. We review protein
      carbohydrate complexes having defined molecular requirements for specific
      carbohydrate recognition by proteins, providing an overview of the different
      computational techniques available to model them.

PMID- 16001417
TI  - Comparison of sequence and structure-based datasets for nonredundant structural
      data mining.
AB  - Structural data mining studies attempt to deduce general principles of protein
      structure from solved structures deposited in the protein data bank (PDB). The
      entire database is unsuitable for such studies because it is not representative
      of the ensemble of protein folds. Given that novel folds continue to be
      unearthed, some folds are currently unrepresented in the PDB while other folds
      are overrepresented. Overrepresentation can easily be avoided by filtering the
      dataset. PDB_SELECT is a well-used representative subset of the PDB that has been
      deduced by sequence comparison. Specifically, structures with sequences that
      exhibit a pairwise sequence identity above a threshold value are weeded from the
      dataset. Although length criteria for pairwise alignments have a structural
      basis, this automated method of pruning is essentially sequence-based and runs
      into problems in the twilight zone, possibly resulting in some folds being
      overrepresented. The value-added structure databases SCOP and CATH are also a
      potential source of a nonredundant dataset. Here we compare the sequence-derived
      dataset PDB_SELECT with the structural databases SCOP (Structural Classification
      Of Proteins) and CATH (Class-Architecture-Topology-Homology). We show that some
      folds remain overrepresented in the PDB_SELECT dataset while other folds are not
      represented at all. However, SCOP and CATH also have their own problems such as
      the labor-intensiveness of the update process and the problem of determining
      whether all folds are equally or sufficiently distant. We discuss areas where
      further work is required.

PMID- 16001418
TI  - Hypocrea jecorina (Trichoderma reesei) Cel7A as a molecular machine: A docking
      study.
AB  - Hypocrea jecorina (formerly Trichoderma reesei) Cel7A has a catalytic domain (CD)
      and a cellulose-binding domain (CBD) separated by a highly glycosylated linker.
      Very little is known of how the 2 domains interact to degrade crystalline
      cellulose. Based on the interaction energies and forces on cello-oligosaccharides
      computationally docked to the CD and CBD, we propose a molecular machine model,
      where the CBD wedges itself under a free chain end on the crystalline cellulose
      surface and feeds it to the CD active site tunnel. Enzyme-substrate interactions
      produce the forces required to pull cellulose chains from the surface and also to
      help the enzyme move on the cellulose chain for processive hydrolysis. The energy
      to generate these forces is ultimately derived from the chemical energy of
      glycosidic bond breakage.

PMID- 16001419
TI  - The betaalphabetaalphabeta elementary supersecondary structure of the Rossmann
      fold from porcine lactate dehydrogenase exhibits characteristics of a molten
      globule.
AB  - Protein classifications show that the Rossmann fold, which consists of two
      betaalphabetaalphabeta motifs (BABAB) related by a rough twofold axis, is the
      most populated alphabeta fold, and that the betaalphabeta submotif (BAB) is a
      widespread elementary structural arrangement. Herein, we report MD simulations,
      circular dichroism and NMR analyses on BAB and BABAB from porcine lactate
      dehydrogenase to evaluate their intrinsic stability. Our results demonstrate that
      BAB is not stable in solution and is not a folding nucleus. We also find that
      BABAB, despite its appearance of a functional and structural unit, is not an
      independent and thermodynamically stable folding unit. Rather, we show that BABAB
      retains most native secondary structure but very little tertiary structure, thus
      displaying characteristics of a molten globule.

PMID- 16001420
TI  - Characterization of cortical neuron outgrowth in two- and three-dimensional
      culture systems.
AB  - To improve the ability of regeneration by grafting living cells or by adding
      growth factor to a lesion site, it is important to find good biomaterials for
      neuron survival and regeneration. This study focused on two- and three
      dimensional cultures in a matrix using biomaterials such as agarose, collagen,
      fibrin, and their mixtures, because these are considered to be suitable
      biomaterials for neuron outgrowth. Cortical neurons were dissected from E17 rat
      embryos and cultured in agarose gel, collagen gel, fibrin glue, and mixtures of
      collagen and fibrin. Results showed that neurons cultured in collagen gel and
      fibrin glue had longer periods of survival (more than 3 weeks) and better neurite
      extension than those observed in agarose gels. As to the survival rate according
      to the MTT and lactate dehydrogenase assays, fibrin glue was the most suitable
      biomaterial for neuron survival among the biomaterials examined. With two
      dimensional fibrin plating, neuron cells exhibited cell aggregation and stress
      fibers, but the same results were not observed with collagen gel. There were no
      differences in neurite extension and survival in the mixtures of collagen and
      fibrin. The results suggest that collagen and fibrin can provide a suitable
      substrate for a three-dimensional culture matrix for neuronal survival and
      differentiation.

PMID- 16001421
TI  - In vitro response of MC3T3-E1 pre-osteoblasts within three-dimensional apatite
      coated PLGA scaffolds.
AB  - Biomimetic apatites have been reported to promote osteogenic activities in
      numerous in vivo and in vitro models, but the precise mechanism by which the
      apatite microenvironment promotes such activities is not well understood. Such
      mechanistic studies require reproducible model systems that are relevant to
      tissue engineering practices. Although two-dimensional (2D) apatite-coated
      polystyrene culture dishes provide practicality and reproducibility, they do not
      simulate the effects of the three-dimensional (3D) microenvironment and degrading
      polymeric substrates. A simple 3D model system to address these relevant effects,
      and its utilization in the investigation of apatite-promoted osteoblastic
      differentiation in vitro is reported in this paper. Apatite coating was achieved
      by sequentially immersing poly(lactide-co-glycolide) (PLGA) scaffolds into
      different simulated body fluids (SBF). SEM, EDX, FTIR, TEM electron diffraction
      confirmed the apatite coating to comprise of calcium-deficient carbonated
      hydroxyapatite crystals. While both apatite-coated and non-coated PLGA scaffolds
      supported MC3T3-E1 attachment, spreading, and proliferation, significant
      differences in osteoblastic differentiation were observed. Relative to non-coated
      controls, quantitative real-time PCR revealed significant apatite-associated
      suppression of alkaline phosphatase (ALP), early upregulation of osteopontin
      (OPN) at 3 days, and upregulation of osteocalcin (OCN) and bone sialoprotein
      (BSP) at 4 weeks. In summary, apatite-promoted osteoblastic differentiation can
      be observed in a 3D model system that is relevant to tissue engineering.

PMID- 16001422
TI  - Polyamide/silver antimicrobials: effect of filler types on the silver ion
      release.
AB  - The efficiency of various silver-based antimicrobial fillers (elementary silver
      and silver substituted materials) in polyamide (PA) toward their silver ion (Ag+)
      release characteristics in an aqueous medium was investigated and discussed.
      Anode stripping voltammetry (ASV) was used for the quantitative estimation of Ag+
      release from these composites. The biocidal (Ag+) release from the composites was
      found to be dependent on the time of soaking in water and the nature of the
      filler. The long-term Ag+ release capability of the elementary silver-based PA/Ag
      composite is promising compared with the commercial counterparts. The silver ion
      release potential of polyamide composites where the silver filling was performed
      by using supercritical carbon dioxide (scCO2) is also discussed. The composites
      release Ag+ at a concentration level capable of rendering antimicrobial efficacy
      and proved to be active against the microbes. A good agreement exists between the
      Ag+ release experiments and antimicrobial test results. The observed results on
      the influence of the nature of the filler and crystallinity on the biocidal
      release and the varying long-term release properties could be helpful in the
      design of industrially relevant biomaterials.

PMID- 16001423
TI  - The significance of autophagy in cancer.
AB  - Autophagy, a vacuolar process of cytoplasmic degradation, is implicated in a form
      of programmed cell death distinct from apoptosis. The regulation of autophagy is
      complex and signalling pathways such as the target of rapamycin (Tor) kinase
      pathway, play important roles in tumourigenesis. Beclin 1, an autophagic protein,
      has been found to be a tumour suppressor. Conversely, cancer cells may exploit
      autophagy as a means to adapt to hypoxic and nutrient-limiting environments. The
      relative importance of autophagic cell death and apoptosis in carcinogenesis
      remains to be established, and the Bcl-2 family of proteins may be instrumental
      in coordinating the two pathways of programmed cell death.

PMID- 16001424
TI  - Butyrate regulates the expression of c-Src and focal adhesion kinase and inhibits
      cell invasion of human colon cancer cells.
AB  - Epidemiological studies indicate that dietary fiber-derived fermentation products
      such as butyrate can prevent colon cancer development. To further dissect the
      role of butyrate in anticarcinogenesis, its effect on cellular growth and
      invasion as well as the expression of c-Src and FAK, two mutually interactive
      nonreceptor tyrosine kinases, in three different human colon cancer cell lines
      (Caco-2, SW480, and SW620) were investigated. In addition to growth inhibition,
      butyrate treatment results in a significant downregulation of c-Src and FAK in
      human colon cancer cells, which can be attributable to their reduced transcripts
      and implicates the participation of a butyrate-sensitive pathway in modulating
      their expression. Concurrent to butyrate-reduced c-Src and FAK expression is the
      decrease of FAK Tyr-decrease 397 phosphorylation. Besides, butyrate also
      abolished the secretion of MMP-2 and MMP-9. And these butyrate-mediated effects
      severely impaired invasion of SW620 cells through Matrigel in vitro.
      Interestingly, in situ parallel enhancement of c-Src and FAK was also observed in
      human colorectal tumor specimens. These results imply that by virtue of
      suppression of c-Src and FAK along with other butyrate targets in colonocytes,
      butyrate could effectively inhibit tumor growth and invasion.

PMID- 16001425
TI  - CHOP plays a pivotal role in the astrocyte death induced by oxygen and glucose
      deprivation.
AB  - Ischemia has different consequences on the survival of astrocytes and neurons.
      Thus, astrocytes show a remarkable resistance to short periods of ischemia that
      are well known to cause neuronal death. We have used a cell culture model of
      stroke, oxygen, and glucose deprivation (OGD), to clarify the mechanisms
      responsible for the exclusive resistance of astrocytes to ischemia. The
      expression of genes implicated in both ischemia-induced astrocyte death and post
      ischemic survival was analysed by the RNA differential display technique. Our
      study revealed that the expression of the CEBP homologous protein (CHOP)-coding
      gene is promptly an intensely upregulated following astrocyte oxygen and glucose
      deprivation. CHOP mRNA induction was accompanied by the activation of other genes
      (grp78, grp95) that, alike CHOP, are involved in the endoplasmic reticulum (ER)
      stress response. In addition, drugs that cause ER calcium depletion or protein N
      glycosylation inhibition mimicked the effects of OGD on astrocyte survival,
      further supporting the involvement of ER in the astrocyte responses to OGD. Our
      experiments also demonstrated that upregulation of CHOP during the ER stress
      response is required for ischemia to cause astrocyte death. Not only the levels
      of CHOP mRNA and protein correlate perfectly with the degree of OGD-triggered
      cell injury, but also astrocyte death induced by OGD is significantly overcome by
      CHOP antisense oligonucleotide treatment. Nevertheless, we observed that
      astrocytes undergo apoptosis only when CHOP is permanently upregulated, and not
      when CHOP increases are transient. Finally, we found that the extent of CHOP
      induction is determined by the length of the ischemic stimulus. Taken together,
      our results indicate that permanent upregulation of CHOP is decisive for the
      induction of astrocyte death by OGD.

PMID- 16001426
TI  - Pyruvate protects glucose-deprived Muller cells from nitric oxide-induced
      oxidative stress by radical scavenging.
AB  - The cellular defense of Muller cells against oxidative and nitrosative stress was
      examined after the addition of the nitric oxide donor papanonoate. Glucose
      concentrations of > or = 550 microM efficiently protected the Muller cells from
      cell death by maintaining high ATP and glutathione and allowing only a moderate
      increase of free radicals. Fluorescence-activated cell sorting (FACS) analysis
      showed that 22% of the cells underwent apoptosis whereas necrosis was strongly
      suppressed. Under glucose deprivation, the intracellular concentration of ATP
      declined to 15% after 1 h; glutathione dropped to 50% within 2 h after
      papanonoate addition. Both the number of cells containing excess free radicals
      and the mean concentration of free radicals increased twofold at 0.5-2 h of
      incubation with papanonoate. Cell death switched from prevailing apoptosis to
      massive necrosis and cell viability decreased drastically. Several metabolites of
      glycolysis, gluconeogenesis, and the pentose phosphate pathway were tested with
      respect to their capability to protect the stressed Muller cells. 2 mM pyruvate
      was found to enhance cell viability 1.6-fold predominantly by reducing the
      necrotic cell demise. It could be shown that pyruvate did not act by improving
      the energy status of Muller cells but by scavenging excess free radicals.
      Inhibition of the monocarboxylate transporters in Muller cells by alpha-cyano-4
      hydroxycinnamate abolished this effect. Other 2-ketoacids, like oxalacetate, 2
      ketoglutarate and 2-ketobutyrate had a similar protecting effect as pyruvate.
      Lactate, glutamate, 2-deoxyglucose, and ribose 5-phosphate did not protect Muller
      cells against oxidative and nitrosative stress.

PMID- 16001427
TI  - Adult human subventricular, subgranular, and subpial zones contain astrocytes
      with a specialized intermediate filament cytoskeleton.
AB  - Human glial fibrillary acidic protein-delta (GFAP-delta) is a GFAP protein
      isoform that is encoded by an alternative splice variant of the GFAP-gene. As a
      result, GFAP-delta protein differs from the predominant splice form, GFAP-alpha,
      by its C-terminal protein sequence. In this study, we show that GFAP-delta
      protein is not expressed by all GFAP-expressing astrocytes but specifically by a
      subpopulation located in the subpial zone of the cerebral cortex, the subgranular
      zone of the hippocampus, and, most intensely, by a ribbon of astrocytes following
      the ependymal layer of the cerebral ventricles. Therefore, at least in the sub
      ventricular zone (SVZ), GFAP-delta specifically marks the population of
      astrocytes that contain the neural stem cells in the adult human brain.
      Interestingly, the SVZ astrocytes actively splice GFAP-delta transcripts, in
      contrast to astrocytes adjacent to this layer. Furthermore, we show that GFAP
      delta protein, unlike GFAP-alpha, is not upregulated in astrogliosis. Our data
      therefore indicate a different functional role for GFAP-delta in astrocyte
      physiology. Finally, transfection studies showed that GFAP-delta protein
      expression has a negative effect on GFAP filament formation, and therefore could
      be important for modulating intermediate filament cytoskeletal properties,
      possibly facilitating astrocyte motility. Further studies on GFAP-delta and the
      cells that express it are important for gaining insights into its function during
      differentiation, migration and during health and disease.

PMID- 16001428
TI  - Design of improved protein inhibitors of HIV-1 cell entry: Optimization of
      electrostatic interactions at the binding interface.
AB  - Continuum electrostatic methods are a powerful tool for the analysis and design
      of biomolecular complexes, with methodologies that allow for the detailed
      analysis of the electrostatic contributions to binding affinities and procedures
      for computing the properties of electrostatically optimal ligands. We have
      applied these methods to the design of improved inhibitors of HIV-1 cell entry.
      HIV infection of a cell requires viral-cell membrane fusion, an event partially
      driven by a large-scale conformational change in the viral membrane glycoprotein
      gp41. This transformation involves the docking of a helix from the C-terminal
      region of three gp41 chains against a pre-formed trimeric-coiled coil; several
      protein constructs that inhibit membrane fusion act by binding to an isolated C
      terminal helix and blocking the formation of the fusogenic structure. A detailed
      analysis of the electrostatic contributions to the binding of one such inhibitor
      (5-Helix) to a C-terminal helix was performed using the X-ray crystal structure
      of the core of the HIV-1 gp41 ectodomain as a structural model, and several
      residues on 5-Helix that make substantial contributions to binding, both
      favorable and unfavorable, were identified. An electrostatic affinity
      optimization methodology was applied to the side chains of 5-Helix, with the
      results showing that significant improvements in binding affinity are possible if
      the electrostatic contributions to the binding free energy are optimized. Several
      mutations accessible by experimental methods are suggested, with calculated
      improvements in binding affinity of as much as 500-fold and greater.

PMID- 16001429
TI  - Movement disorder of the lower lip.

PMID- 16001430
TI  - Identification of individual genes altered in squamous cell carcinoma of the
      vulva.
AB  - Chromosome rearrangements in squamous cell carcinoma of the vulva (SCV) have
      indicated common consistent regions of loss and gain. The overall aim of our
      research was to define and characterize individual genes that underlie the
      pathogenesis of SCV. Thirteen cell lines from 12 SCV patients were evaluated for
      loss and gain of 122 genes distributed throughout the genome. Individual genes
      were analyzed for genetic alterations using a novel genomewide strategy, the
      multiplex ligation-dependent probe amplification assay. Our candidate gene
      approach identified several altered loci. Most frequent was the loss of 1 copy of
      TMSB10, observed in 11 of 12 SCV patients, followed by loss of CTNNB1 and BCL2,
      which occurred in 7 of 12 patients. Frequent gains/amplifications included CCND1,
      observed in 8 of 12 patients, and IL12A, in 7 of the 12 patients. Loss and gain
      of specific genes observed in our study were generally concordant with the
      results of previous studies of cytogenetics and CGH utilizing the same SCV cell
      lines. Genetic alterations are hallmarks of tumorigenesis, and there is wide
      agreement that recurrent altered genomic loci contain genes important for tumor
      development and progression. Understanding the interplay of cancer genes and the
      pathways they utilize can lead to the detection of novel molecular targets in the
      diagnosis, prognosis, and treatment of SCV.

PMID- 16001431
TI  - A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a
      patient with a clinically typical chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is characterized by the presence of a
      t(9;22)(q34;q11.2), which leads to the well-known BCR-ABL1 fusion protein. We
      describe a patient who was diagnosed clinically with a typical CML but on
      cytogenetic analysis was found to have a t(9;22)(p24;q11.2). Chromosomal
      fluorescence in situ hybridization showed that the BCR gene locus spanned the
      breakpoint at band 22q11.2 but that the ABL1 gene was not rearranged. By means of
      a candidate gene approach, the JAK2 gene, at 9p24, was identified as the fusion
      partner of BCR in this case. The BCR-JAK2 fusion protein contains the coiled-coil
      dimerization domain of BCR and the protein tyrosine kinase domain (JH1) of JAK2.
      The patient's disease did not respond to Imatinib, and this unresponsiveness was
      most likely a result of the BCR-JAK2 fusion protein.

PMID- 16001433
TI  - Delineation of distinct subgroups of multiple myeloma and a model for clonal
      evolution based on interphase cytogenetics.
AB  - To delineate multiple myeloma (MM) subgroups and their clonal evolution, we
      analyzed 81 newly diagnosed patients by interphase fluorescence in situ
      hybridization using a comprehensive probe set for 10 chromosomes and two IGH
      rearrangements. A median of 5 probes per patient displayed aberrant signal
      numbers (range, 1-10). Additional copies most frequently found were for 15q22,
      19q13, 9q34, 11q23, and 1q21. Losses commonly observed were of 13q14.3, 17p13,
      and 22q11. Predominance of gain or loss was quantified by a copy number score
      (CS) for each patient. Two peaks (CS = +3 and CS = 0) were found by plotting
      patient copy number scores over CS values corresponding to hyperdiploid and
      nonhyperdiploid MM. Cluster analysis revealed four major branches: (i) gain of
      9q, 15q, 19q, and/or 11q; (ii) deletion of 13q and t(4;14); (iii) t(11;14); and
      (iv) gain of 1q. Statistical modeling of an oncogenetic tree indicated that early
      independent events were gain of 15q/9q and/or 11q, t(11;14); deletion of 13q
      followed by t(4;14); and gain of 1q. Aberrations of 17p13, 22q11, 8p12, and 6q21
      were found as subsequent events. MM with gain of 1q was delineated as a subentity
      with significantly higher beta-2-microglobulin and lower hemoglobin levels,
      indicating a poor prognosis. From our results, we propose a model of MM for
      clonal evolution.

PMID- 16001432
TI  - IGF2/H19 imprinting analysis of human germ cell tumors (GCTs) using the
      methylation-sensitive single-nucleotide primer extension method reflects the
      origin of GCTs in different stages of primordial germ cell development.
AB  - Previous studies have demonstrated biallelic expression of the imprinted genes
      H19 and IGF2 and loss of DNA methylation of the SNRPN gene, indicating a common
      precursor cell of human germ cell tumors (GCTs), namely, the primordial germ cell
      (PGC). In this study, we applied the methylation-sensitive single-nucleotide
      primer extension (MS-SNuPE) technique to the analysis of the IGF2/H19 imprinting
      control region (ICR) in 55 GCTs from representative clinical and histologic
      subgroups. Most GCTs showed low methylation at the IGF2/H19 ICR. All 8 ovarian
      GCTs, 9 of 10 testicular seminomas, 7 of 10 testicular nonseminomas (all in
      adolescents/adults), 6 of 9 testicular yolk sac tumors (YSTs), and 12 of 14
      nongonadal GCTs (all in infants/children) were hypomethylated. The highest
      methylation was observed in three childhood YSTs (boys) and 2 of 4 spermatocytic
      seminomas. The latter are derived from more advanced stages of germ-cell
      development. The predominantly low methylation of most of the other GCTs
      correlates with studies that demonstrated erasure of the methylation imprint of
      the IGF2/H19 ICR during embryonal PGC migration and development. These findings
      suggest that the IGF2/H19 methylation status in GCTs might reflect preservation
      of the physiologic imprinting erasure in PGCs rather than a loss of imprinting in
      a sense that is accepted for somatic tumors. Furthermore, this study indicates
      that imprinting control mechanisms other than the proposed CTCF (CCCTC binding
      factor) boundary model regulate IGF2 expression during this stage of PGC
      development as well as in GCTs derived from PGC. (c) 2005 Wiley-Liss, Inc.

PMID- 16001434
TI  - Molecular and immunohistochemical investigation of protein kinase a regulatory
      subunit type 1A (PRKAR1A) in odontogenic myxomas.
AB  - Odontogenic myxomas are rare benign neoplasms affecting the jaw. Myxomas of bones
      and other sites occur as part of Carney complex (CNC), a multiple neoplasia
      syndrome caused by mutations in the PRKAR1A gene, which codes for the regulatory
      subunit of protein kinase A (PKA). In the present study, 17 odontogenic myxomas
      from patients without CNC were screened for PRKAR1A mutations and PRKAR1A protein
      expression by immunohistochemistry (IHC). Mutations of the coding region of the
      PRKAR1A gene were identified in 2 tumors; both these lesions showed no or
      significantly decreased immunostaining of PRKAR1A in the tumor compared to that
      in the surrounding normal tissue. One mutation (c.725C>A) led to a
      nonconservative amino acid substitution in a highly conserved area of the gene
      (A213D); the other was a single base-pair deletion that led to a frameshift
      (del774C) and a stop codon 11 amino acids downstream of the mutation site; both
      tumors were heterozygous for the respective mutations. Of the remaining tumors, 7
      of the 15 without mutations showed almost no PRKAR1A in the tumor cells, whereas
      IHC showed that the protein was abundant in nontumorous cells. We concluded that
      PRKAR1A may be involved by its down-regulation in the pathogenesis of odontogenic
      myxomas caused by mutations and/or other genetic mechanisms. Of the sporadic,
      nonfamilial tumors associated with PRKAR1A mutations, the odontogenic type was
      the first myxomatous lesion found to harbor somatic PRKAR1A sequence changes.

PMID- 16001435
TI  - Re: distal arthrogryposis in two sisters born to different fathers [Hwu et al.
      2004. Am J Med Genet 125A:100-101.].

PMID- 16001436
TI  - Tetralogy of fallot in a patient with developmental coxa vara/spondylometaphyseal
      dysplasia-corner fracture type (DCV/SMD-CF) expanding the variability.

PMID- 16001437
TI  - Re: polymicrogyria versus pachygyria in 22q11 microdeletion.

PMID- 16001438
TI  - 550delA mutation in the calpain 3 (CAPN3) gene: DMD/BMD, SMA, or LGMD2A-
      clinically misdiagnosed cases.

PMID- 16001439
TI  - Craniosynostosis: another feature of the 22q11.2 deletion syndrome.
AB  - We report on the presence of craniosynostosis in four patients with the 22q11.2
      deletion. In light of previous reports of the association, we propose that the
      occurrence is higher than the general population incidence. Therefore, we suggest
      that craniosynostosis should be considered a manifestation of the 22q11.2
      deletion and conversely that the 22q11.2 deletion should be considered in the
      differential diagnosis of craniosynostosis.

PMID- 16001440
TI  - Novel karyotypic changes detected by comparative genomic hybridization in a case
      of congenital cervical immature teratoma.
AB  - BACKGROUND: Cervical immature teratoma is a rare congenital tumor, and very few
      cases have been studied cytogenetically. CASE: In this article, we describe a
      case of this tumor type and present the findings of the karyotype of the lesion,
      which was performed with the bacterial artificial chromosome arrays using the
      comparative genomic hybridization method. The chromosomal abnormalities that we
      found included an amplification on 1p21.1, a 9p22 deletion, and a 1-copy gain of
      17q21.33. CONCLUSIONS: None of the identified chromosomal aberrations have been
      previously associated with congenital extragonadal teratomas. Important genes
      that lie in these DNA regions may be implicated in the pathogenesis of congenital
      teratomas.

PMID- 16001441
TI  - Functional magnetic resonance imaging response to increased verbal working memory
      demands among patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) patients frequently experience impaired verbal working
      memory (VWM). Functional magnetic resonance imaging (fMRI) may help identify
      neural mechanisms underlying these deficits. Neuroimaging studies of healthy
      adults have characterized responses associated with increased VWM demands during
      the n-Back task, suggesting that this experimental paradigm could help identify
      neural correlates of VWM deficits among MS patients. Fifteen MS patients and 15
      matched control participants completed the n-Back during whole-brain fMRI. Mean
      signal during adjacent 0-Back blocks was subtracted, on a voxel-wise basis, from
      mean signal observed during n-Back blocks. Resulting difference scores for 1-, 2
      , and 3-Back were compared across groups and difficulty levels. Signal intensity
      was positively related to difficulty level in anterior regions, including
      premotor, supplementary motor, and dorsolateral prefrontal cortices. MS patients
      exhibited significantly greater intensity in these areas compared to controls
      during the 1-Back, while portions of the left superior frontal gyrus, cingulate,
      and parahippocampal gyri were relatively less intense at more difficult levels.
      MS group responses were slower during the 1-Back and tended to be slower during
      the 3-Back; however, accuracy did not differ at any level. Lesion load was
      positively related to only 1-Back activity and unrelated to any performance
      measure. Results suggest that compensatory activity occurs among MS patients
      matched on performance accuracy. Furthermore, compensatory activity occurs
      predominantly in regions associated with VWM, and this may decline relative to
      controls as task demands increase. These findings may help to explain why MS
      patient performance decreases as a function of effort on neuropsychological
      tests.

PMID- 16001442
TI  - X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly,
      hydrocephaly, and microphthalmia.
AB  - We describe a family with an X-linked dominant chondrodysplasia. Four males and
      six females were affected through four generations. Identification of skeletal
      abnormalities and hydrocephaly during the pregnancy of three male fetuses led to
      termination of the pregnancies. A fourth affected male died at 6 days of life.
      The four patients had chondrodysplasia, hydrocephaly, and facial features with
      microphthalmia. Radiographs showed severe platyspondyly and various bone
      abnormalities including a distinctive metaphyseal cupping of the metacarpals,
      metatarsals, and phalanges. The affected females were less affected and showed
      small stature, sometimes associated with body asymmetry and mild mental
      retardation. This condition appears to be a previously unrecognized X-linked
      dominant chondrodysplasia.

PMID- 16001443
TI  - Trisomy of the short arm of chromosome 5 due to a de novo inversion and
      duplication (5)(p15.3 p13.3).
AB  - Partial trisomies of the short arm of chromosome 5 are uncommon. The first
      description was made by Lejeune et al., in 1964. It has been suggested that the
      critical region for 5p trisomy syndrome lies between 5p10 and 5p13. We report on
      a Mexican girl who developed severe mental retardation and generalized tonic
      clonic seizures at age 1 year. On physical examination at age 5 years, she had
      macrodolichocephaly, upslanted palpebral fissures, bilateral inner epicanthic
      folds, low nasal root, and malformed ears with posterior rotation which are
      clinical characteristics of 5p trisomy syndrome. The cytogenetic study with G
      bands and FISH with painting for chromosome 5 and with the cri-du-chat 5p15
      unique sequence probe showed a duplication and inversion of 5p [46,XX,
      dup(5)(p15.3 p13.3)] which overlaps with the critical region for 5p trisomy
      syndrome. Our patient shares clinical characteristics with the patients described
      in the literature with involvement of this critical region. Both parents have
      normal karyotypes indicating the rearrangement is de novo. Only one patient has
      been reported in the literature with the same cytogenetic rearrangement as our
      patient, but this patient had a different phenotype. Since they only performed
      conventional cytogenetics and we performed FISH to confirm the diagnosis, the
      differences in the phenotypes could be explained by the presence of other genes
      involved in the rearrangement. The combined use of conventional and molecular
      cytogenetics in this case allows a more precise diagnosis and furthers knowledge
      in phenotype/genotype correlation.

PMID- 16001444
TI  - Speech-language characteristics of children with Sotos syndrome.
AB  - The purpose of this research study was to evaluate the communication of
      individuals with Sotos syndrome in order to better characterize common speech and
      language patterns. Sixteen children with Sotos syndrome received an in-depth
      communication assessment using standardized procedures. Assessments of speech
      skills, language skills, voice, fluency, and social-pragmatic interactions were
      completed. Results of the evaluations indicated that individuals with Sotos
      syndrome are prone to: (a) language impairments (particularly expressive), (b)
      speech sound production impairments, (c) voice impairments, (d) dysfluencies
      (stuttering), and (e) average social-behavioral pragmatic interaction
      characteristics.

PMID- 16001445
TI  - Sex-specific chromosome instability in early human development.
AB  - The predominance of females segregating chromosome aberrations to their offspring
      has been explained mostly by selection disadvantage of unbalanced products of
      spermatogenesis. However, analysis of data from the literature supports the idea
      that somatic cells of early female embryos are similar to female germ cells in
      that they are prone to malsegregation. The goal of this study was to compare the
      sex ratio (male to female ratio) of carriers of presumably mitotic-occurring
      chromosome abnormalities to identify any sex biases. In examining the literature,
      we found a female prevalence in cases of mosaicism associated with uniparental
      disomy (UPD) (26 male individuals/conceptions and 45 female
      individuals/conceptions, sex ratio is 0.58, significantly different from 1.06 in
      newborn population, P = 0.0292). This predominance was highest at gestational age
      <16 week (8 male and 22 female conceptuses, sex ratio is 0.36, significantly
      different from expected figure of 1.28, P = 0.0025), which diminished at later
      stages of fetal development indicating potential correction of trisomies
      predominantly in females. There is a threefold prevalence of 46,XX/45,X mosaics
      over 46,XY/45,X mosaics in prenatally diagnosed cases, which also suggests a
      gender-specific postzygotic chromosome loss. The male prevalence in Prader-Willi
      syndrome with maternal UPD of chromosome 15 also can be explained by sex-specific
      trisomy correction, with predominant loss of a maternal chromosome causing
      biparental inheritance and therefore, complete correction of trisomy in females
      (without UPD). Finally, there is a female predominance in carriers of chromosome
      rearrangement with pericentromere break (mosaicism for Robertsonian
      translocation/isochromosome, centric fission, nonacrocentric isochromosome, and
      whole arm rearrangement), in both prenatal (21 males and 36 females, sex ratio is
      0.58, P < 0.0184) and postnatal ill-defined cases (14 males and 35 females, sex
      ratio is 0.40, P = 0.001). Thus, the findings presented in this paper suggest
      that, in addition to reduction in male fertility, and to probable selection
      against abnormal cell line(s), there are two mechanisms that contribute to female
      preponderance among carriers of mosaicism: sex-specific chromosome loss and sex
      specific centromere instability. The data obtained suggest that females may have
      gonadal mosaicism for aneuploidies and structural rearrangements more often than
      males. This may lead to the maternal origin bias in offspring with trisomies or
      structural rearrangements.

PMID- 16001446
TI  - Bilateral congenital diaphragmatic hernia with absent pleura and pericardium.
AB  - BACKGROUND: Bilateral congenital diaphragmatic hernia is a rare form of
      diaphragmatic hernia. Independently, pericardial defects are an extremely rare
      phenomenon. In the case presented, we provide the first complete description of
      an infant with bilateral congenital diaphragmatic hernia with complete agenesis
      of the pericardium and inferior parietal pleura. CASE: A male infant was born at
      38 weeks of gestation with a prenatal diagnosis of left-sided congenital
      diaphragmatic hernia. After 1 week of aggressive management, the patient was
      taken to the operating room for repair. Intraoperatively, the patient was found
      to have absence of the diaphragm bilaterally, no pleura inferiorly, and no
      pericardium. A biological mesh was used to construct a diaphragm. At 6 months of
      age, the patient is growing normally, requiring only supplemental oxygen without
      pressure support. CONCLUSIONS: Embryologically, this anomaly represents complete
      lack of development of the pleurocardial folds, pleuroperitoneal folds, and
      transverse septum, which is previously unreported.

PMID- 16001447
TI  - Testing the autogenous-reactive model of obsessions.
AB  - Two independent studies were conducted to examine the autogenous-reactive subtype
      model of obsessions [Lee and Kwon, 2003]. Study 1 demonstrated that 30 obsessive
      compulsive (OCD) patients' responses to autogenous versus reactive obsessions
      differed significantly with respect to emotional reactions, cognitive appraisals,
      and control strategies. Study 2 compared OCD patients whose primary obsessions
      were of the autogenous subtype (n=13) with OCD patients whose primary obsessions
      were of the reactive subtype (n=14). Results revealed significant differences
      between these two groups on several OCD-related domains including OCD symptom
      profiles, perfectionistic personality features, and dysfunctional beliefs.
      Theoretical and clinical implications are discussed.

PMID- 16001448
TI  - Effects of the cortisol synthesis inhibitor metyrapone on the response to carbon
      dioxide challenge in panic disorder.
AB  - Despite the well-known association between the hypothalamic-pituitary-adrenal
      (HPA) axis and normal fear, it is still unclear (a) to what extent corticotropin
      releasing hormone (CRH) or cortisol itself mediates fear responses, and (b) to
      what extent the HPA axis also affects panic disorder. The carbon-dioxide (CO2)
      challenge has been proposed as a model for panic. Participants received the
      cortisol synthesis inhibitor metyrapone 30 mg/kg of body weight once and placebo
      once, with 1 week between challenges, at 2300 h. The following morning, blood was
      taken for cortisol and ACTH levels, and then participants inhaled a single vital
      capacity inhalation of 35% CO2 and 65% oxygen. Before and after the inhalation,
      participants completed an inventory of the 13 DSM-IV symptoms of panic and the
      NIMH questionnaire of psychological and physical symptoms. Eight healthy controls
      and 14 patients with panic disorder completed the protocol. As expected, CO2
      increased measures of anxiety, and metyrapone lowered cortisol and increased ACTH
      levels. Prechallenge anxiety was modestly lowered by metyrapone, but response to
      CO2 was not affected. Cortisol and ACTH levels before challenge partly predicted
      the response to CO2. The results support an anxiogenic role for cortisol in
      stress, and suggest that the pathophysiological mechanism that mediates CO2
      induced panic differs from those underlying other kinds of anxiety.

PMID- 16001449
TI  - Expression and role of Foxa proteins in prostate cancer.
AB  - The molecular mechanism(s) for prostate cancer progression to androgen
      independence are poorly understood. We have recently shown that Foxa1 and Foxa2
      proteins are differentially expressed in epithelial cells during murine prostate
      development, growth, and adult function. Currently, the role of Foxa proteins in
      prostate cancer development and progression is unknown. Foxa protein expression
      was investigated in the LPB-Tag LADY mouse prostate cancer models, in human
      prostate cancer specimens, and various prostate cancer cell lines using Western
      blot and immunostaining analysis. In vitro transient transfection, studies were
      performed to investigate Foxa/prostate-specific gene regulation. Foxa1 was
      strongly expressed in areas of prostatic intraepithelial neoplasia (PIN) in both
      the androgen dependent 12T-7f and in the metastatic, androgen independent 12T-10
      LADY models. Prominent Foxa1 and Foxa2 expression was observed in 12T-10 invasive
      undifferentiated neuroendocrine carcinomas, in the hormone independent and
      metastasizing 12T-10 derived, NE-10 allograft tumors, and in all metastatic
      lesions isolated from 12T-10 mice. Foxa1 protein expression was always observed
      in human prostate carcinomas, regardless of Gleason grade score, while Foxa2 was
      only detected in neuroendocrine small cell carcinomas and in some high Gleason
      score adenocarcinomas. Foxa proteins were also differentially expressed in three
      prostate cancer cell lines. Importantly, in vitro functional assays demonstrated
      that Foxa2 could activate androgen-dependent prostate-specific genes in an
      androgen receptor and ligand-independent manner. These results suggest that Foxa
      proteins are important in prostate carcinogenesis. In particular, Foxa2 may be
      involved in progression of prostate cancer to androgen independence. As such,
      Foxa proteins may represent novel targets for therapeutic intervention.

PMID- 16001450
TI  - Mesoporous silica nanoreactors for highly efficient proteolysis.
AB  - Protein digestion inside the nanoreactor channels of mesoporous silica (SBA-15)
      is reported, and evaluated by using peptide-mass mapping. Both proteases and
      substrates were efficiently captured within these biocompatible nanoreactors.
      After 10 minutes, the mass spectrum of the protein digests released from the
      mesoporous-silica-based nanoreactors revealed the presence of eight peptides
      covering 58% of the protein sequence with an intense signal (signal/noise ratio >
      70). In comparison, the conventional overnight in-solution digestion of proteins
      under otherwise identical conditions generated only three peptides (27% sequence
      coverage). We propose that this order-of-magnitude increase in the proteolytic
      reaction rate is mainly attributed to two factors: substrate enrichment within
      mesoporous silica channels and enzyme immobilization. The surface properties and
      macrostructure of the mesoporous silica were studied to reveal their significant
      influence on proteolytic reactions.

PMID- 16001451
TI  - The Barton reaction: can a more tenable pathway be hypothesized for the formation
      of nitrosoalkyl derivatives?
AB  - Herein, we report that in the formation of nitrosoalkyl derivatives during the
      photolysis of alkyl nitrites, the formation of the intermediate alkyl alkoxy
      nitroxide, due to the trapping of alkyl radicals by the starting nitrite, is the
      key step of the entire process. In fact, these nitroxides, detectable by EPR
      spectroscopy, decay to the final nitroso derivatives under thermodynamic control.
      In light of this, the Barton reaction mechanism has been reviewed. The
      nitrosoalkyl derivatives, or the hydroxamic acids when steroids are involved,
      have now to be considered as the ending products of the entire process and not,
      unless a very high concentration of NO is present in the medium, the result of a
      direct reaction of NO with the alkyl radical, as is commonly accepted.

PMID- 16001452
TI  - Preparation of [5,6]- and [6,6]-oxahomofullerene derivatives and their
      interconversion by Lewis acid assisted reactions of fullerene mixed peroxides.
AB  - [60]Fullerene mixed peroxides C60(O)(OOtBu)4 exhibit chemo- and regioselective
      reactions under mild conditions. The epoxy moiety is opened by ferric chloride to
      form vicinal hydroxy chloride C60Cl(OH)(OOtBu)4. BF3 is also effective in opening
      the epoxy moiety. The O-O bond of the fullerene mixed peroxide is cleaved by
      aluminum chloride to form both [5,6]- and [6,6]-fullerene hemiketals
      (oxohomo[60]fullerenes). A Hock-type rearrangement is proposed for the formation
      of the hemiketals, in which a fullerene C-C bond is cleaved. Lewis acids and/or
      visible light can initiate isomerization of the hemiketal isomers. Single-crystal
      X-ray analysis and theoretical calculations confirmed the results.

PMID- 16001453
TI  - Bioadhesive properties of a polyaminoacidic hydrogel: evaluation by ATR FT-IR
      spectroscopy.
AB  - The bioadhesive properties of a novel chemical hydrogel based on a polymer of
      protein-like structure, have been investigated by using ATR FT-IR spectroscopy.
      In particular, the copolymer PHG obtained by partial derivatization of PHEA with
      GMA was chemically crosslinked by UV irradiation at 313 nm. Crosslinked PHG was
      treated with water to obtain a swelled sample, named PHG-UV gel, that was brought
      into contact with a phosphate buffer/citric acid solution at pH 7.0 in the
      absence or in the presence of mucin at various concentrations (0.01, 0.1 and 1
      wt.-%). Preliminary dynamic swelling studies have evidenced the occurrence of an
      interaction between the PHG-UV gel and the glycoprotein. This result was
      confirmed by ATR FT-IR measurements. A diffusion model using a solution of Ficks'
      second law was employed to determine the diffusion coefficient of water into PHG
      UV gel as a consequence of adsorption and/or interdiffusion which occur at the
      PHG-UV gel/mucin solution interface. Experimental results suggest a potential use
      of PHG-UV gel to prepare bioadhesive devices.

PMID- 16001454
TI  - Encapsulation and controlled release of a hydrophobic drug using a novel
      nanoparticle-forming hyperbranched polyester.
AB  - An amphiphilic, hyperbranched polymer suitable for use in controlled drug
      delivery is reported. This polymer was obtained by modification of the
      hyperbranched aliphatic polyester Boltorn H20 (H20) with succinic anhydride and
      then glycidyl methacrylate, and formed nanoparticles in aqueous solution. The
      critical association concentration was 7.4 x 10(-3) g . L(-1), as determined by
      fluorescence spectroscopy using pyrene as a molecular probe. A static/dynamic
      laser light scattering (LLS) study revealed that the average particle size was
      39.4 nm with a low particle size distribution (PDI=0.04), and that each particle
      was composed of about 350 amphiphilic molecules. Daidzein, a hydrophobic
      traditional Chinese medicine, was encapsulated during particle formation and the
      release properties were determined. The optimal feeding concentration of daidzein
      to hyperbranched polyester was 4.9 x 10(-5) g . mL(-1) to 5.0 x 10(-3) g . mL(-1)
      with a loading efficiency of 76.1%. In the presence of the enzyme Lipase PS, the
      drug loaded nanoparticles degraded in a random one-by-one manner and released the
      drug over a few days. This system is therefore a novel controlled drug release
      system based on nanoparticles formed of hyperbranched polyester. Encapsulation of
      daidzein by hyperbranched polyester particles.

PMID- 16001455
TI  - Backbone amide linker (BAL) strategy for Nalpha-9-fluorenylmethoxycarbonyl (Fmoc)
      solid-phase synthesis of peptide aldehydes.
AB  - A rapid and efficient strategy has been developed for the general synthesis of
      complex peptide aldehydes. N(alpha)-Benzyloxycarbonylamino acids were converted
      to protected aldehyde building blocks for solid-phase synthesis in four steps and
      moderate overall yields. The aldehydes were protected as 1,3-dioxolanes except
      for one case where a dimethyl acetal was used. These protected amino aldehyde
      monomers were then incorporated onto 5-[(2 or 4)-formyl-3,5
      dimethoxyphenoxy]butyryl-resin (BAL-PEG-PS) by reductive amination, following
      which the penultimate residue was introduced by HATU-mediated acylation. The
      resultant resin-bound dipeptide unit, anchored by a backbone amide linkage (BAL),
      was extended further by routine Fmoc chemistry procedures. Several model peptide
      aldehydes were prepared in good yields and purities. Some epimerization of the C
      terminal residue occurred (10% to 25%), due to the intrinsic stereolability
      conferred by the aldehyde functional group, rather than any drawbacks to the
      synthesis procedure.

PMID- 16001456
TI  - Applications of multi-variate analysis of variance (MANOVA) to multi-electrode
      array electrophysiology data.
AB  - We have developed an adaptation of multi-variate analysis of variance (MANOVA) to
      analyze statistically both local and global patterns of multi-electrode array
      (MEA) electrophysiology data where the activities of many (typically >100)
      neurons have been recorded simultaneously. Whereas simple application of standard
      MANOVA techniques prohibits extraction of useful information in this kind of
      data, our new approach, MEANOVA (=MEA+MANOVA), allows a more useful and powerful
      approach to analyze such complex neurophysiological data. The MEANOVA test
      enables the detection of the "hot-spots" in the MEA data and has been validated
      using recordings from the rat olfactory bulb. To further validate the power of
      this approach, we have also applied the MEANOVA test to data obtained from a
      simple computational network model. This MEANOVA software and other useful
      statistical methods for MEA data can be downloaded from
      http://www.sussex.ac.uk/Users/pmh20

PMID- 16001457
TI  - Culture, community, and disease control.

PMID- 16001458
TI  - Impact of the media on adolescent sexual attitudes and behaviors.
AB  - BACKGROUND: Adolescents in the United States are engaging in sexual activity at
      early ages and with multiple partners. The mass media have been shown to affect a
      broad range of adolescent health-related attitudes and behaviors including
      violence, eating disorders, and tobacco and alcohol use. One largely unexplored
      factor that may contribute to adolescents' sexual activity is their exposure to
      mass media. OBJECTIVE: We sought to determine of what is and is not known on a
      scientific basis of the effects of mass media on adolescent sexual attitudes and
      behaviors. Method. We performed an extensive, systematic review of the relevant
      biomedical and social science literature and other sources on the sexual content
      of various mass media, the exposure of adolescents to that media, the effects of
      that exposure on the adolescents' sexual attitudes and behaviors, and ways to
      mitigate those effects. Inclusion criteria were: published in 1983-2004,
      inclusive; published in English; peer-reviewed (for effects) or otherwise
      authoritative (for content and exposure); and a study population of American
      adolescents 11 to 19 years old or comparable groups in other postindustrial
      English-speaking countries. Excluded from the study were populations drawn from
      college students. RESULTS: Although television is subject to ongoing tracking of
      its sexual content, other media are terra incognita. Data regarding adolescent
      exposure to various media are, for the most part, severely dated. Few studies
      have examined the effects of mass media on adolescent sexual attitudes and
      behaviors: only 12 of 2522 research-related documents (<1%) involving media and
      youth addressed effects, 10 of which were peer reviewed. None can serve as the
      grounding for evidence-based public policy. These studies are limited in their
      generalizability by their cross-sectional study designs, limited sampling
      designs, and small sample sizes. In addition, we do not know the long-term
      effectiveness of various social-cultural, technologic, and media approaches to
      minimizing that exposure (eg, V-Chips on television, Internet-filtering-software,
      parental supervision, rating systems) or minimizing the effects of that exposure
      (eg, media-literacy programs). CONCLUSIONS: Research needs to include development
      of well-specified and robust research measures and methodologies; ongoing
      national surveillance of the sexual content of media and the exposure of various
      demographic subgroups of adolescents to that content; and longitudinal studies of
      the effects of that exposure on the sexual decision-making, attitudes, and
      behaviors of those subgroups. Additional specific research foci involve the
      success of various types of controls in limiting exposure and the mitigative
      effects of, for example, parental influence and best-practice media-literacy
      programs.

PMID- 16001459
TI  - Problems and solutions associated with media consumption: the role of the
      practitioner.

PMID- 16001460
TI  - Sex screen: the dilemma of media exposure and sexual behavior.

PMID- 16001461
TI  - SOGC clinical practice guidelines. Uterine fibroid embolization (UFE). Number
      150, October 2004.
AB  - OBJECTIVE: To help direct the organized and effective implementation of uterine
      fibroid embolization into clinical practice in Canada. OPTIONS: This document is
      restricted to the management of uterine fibroid embolization as performed by the
      radiologists utilizing a transfemoral artery approach with arteriography followed
      by vessel embolization. OUTCOMES: Uterine fibroid embolization has been evaluated
      in terms of patient satisfaction, risks of complications, risks in subsequent
      pregnancy and rate of hysterectomy within a few months of the procedure. As the
      procedure is relatively new, data on long-term outcomes are not available.
      EVIDENCE: Published opinions of experts, supplemented by evidence from clinical
      trials where appropriate. VALUES: The quality of the evidence is rated using the
      criteria described by the Canadian Task Force on the Periodic Health Examination.
      BENEFITS, HARMS, AND COSTS: For women presenting with symptomatic uterine
      fibroids who are candidates for UFE, there is often a benefit to avoiding an
      abdominal surgery. The risks of theUFE procedure, possible complications, and
      short- and long-term prognosis must be measured on an individual basis against
      the well studied surgical alternatives. Patient preference is an important
      component of this evaluation. The non-material costs of on going symptoms from
      the fibroids are difficult to measure and use comparatively against the cost of
      hospitalization and treatment. In evaluating costs of UFE, the calculations
      should take into consideration the cost of managing occasional complications
      including subsequent hysterectomy. The cost of myomectomy or hysterectomy will
      vary largely depending on technique used and length of hospital stay.
      RECOMMENDATIONS: 1. Women considering treatment of fibroids should be counselled
      that while the early results of uterine artery embolization are encouraging, no
      long-term data exist. (II-2-B). 2.UFE should only be considered for women with
      symptomatic or problematic fibroids who might otherwise be advised to have
      surgical treatment. (III-A). 3. UFE as a treatment for fibroids inpatients
      wishing to preserve their fertility should be undertaken with full disclosure to
      the patient about the limitations of such a procedure and the lack of existing
      data regarding future fertility and pregnancy outcomes. (III-C). 4. UFE is
      contraindicated in women who have evidence of current genitourinary infection
      and/or malignancy. (II-2-B). 5. Women who choose UFE as an alternative to
      hysterectomy should be counselled regarding the risk of major complications of
      UFE where hysterectomy may be urgently required and potentially lifesaving. In
      view of this small but important risk, UFE is relatively contraindicated in women
      who are unwilling to have a hysterectomy under any circumstances. (III-C). 6.
      Genitourinary infection is the predominant cause of serious morbidity and
      mortality. Further research on the utility of prophylactic antibiotic therapy and
      the value of pretreatment screening for infection is needed. (II-2-B). 7. A
      gynaecologist who is familiar with UFE should evaluate all patients considered
      for UFE before the procedure is booked and a consensus on the suitability of the
      procedure achieved between the gynaecologist and radiologist. (III-C). 8. Only
      radiologists with specialized embolization experience and techniques should
      perform UFE. (III-C). 9. The particular responsibilities of both gynaecologist
      and radiologist should be established prior to treatment and be set out in a
      relevant hospital protocol. A particular physician must be responsible for the
      patient at all times. (III-C). 10. A Canadian national registry of numbers,
      indications,outcomes, complications, and successful pregnancies associated with
      UFE should be created and jointly administered and funded by the SOGC, CAR, and
      CIRA. (III-C).

PMID- 16001462
TI  - SOGC clinical practice guidelines. Guidelines for vaginal birth after previous
      caesarean birth. Number 155 (Replaces guideline Number 147), February 2005.
AB  - OBJECTIVE: To provide evidence-based guidelines for the provision of a trial of
      labor (TOL) after Caesarean section. OUTCOME: Fetal and maternal morbidity and
      mortality associated with vaginal birth after Caesarean (VBAC) and repeat
      Caesarean section. EVIDENCE: MEDLINE database was searched for articles published
      from January 1, 1995, to February 28, 2004, using the key words "vaginal birth
      after Caesarean (Cesarean) section". The quality of evidence is described using
      the Evaluation of Evidence criteria outlined in the Report of the Canadian Task
      Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Provided there are no
      contraindications, a woman with 1 previous transverse low-segment Caesarean
      section should be offered a trial of labor (TOL) with appropriate discussion of
      maternal and perinatal risks and benefits. The process of informed consent with
      appropriate documentation should be an important part of the birth plan in a
      woman with a previous Caesarean section (II-2B). 2. The intention of a woman
      undergoing a TOL after Caesarean section should be clearly stated, and
      documentation of the previous uterine scar should be clearly marked on the
      prenatal record (II-2B). 3. For a safe labor after Caesarean section, a woman
      should deliver in a hospital where a timely Caesarean section is available. The
      woman and her health care provider must be aware of the hospital resources and
      the availability of obstetric, anesthetic, pediatric, and operating-room staff
      (II-2A). 4. Each hospital should have a written policy in place regarding the
      notification and (or) consultation for the physicians responsible for a possible
      timely Caesarean section (III-B). 5. In the case of a TOL after Caesarean, an
      approximate time frame of 30 min should be considered adequate in the set-up of
      an urgent laparotomy (IIIC). 6. Continuous electronic fetal monitoring of women
      attempting a TOL after Caesarean section is recommended (II-2A). 7. Suspected
      uterine rupture requires urgent attention and expedited laparotomy to attempt to
      decrease maternal and perinatal morbidity and mortality (II-2A). 8. Oxytocin
      augmentation is not contraindicated in women undergoing a TOL after Caesarean
      section (II-2A). 9. Medical induction of labor with oxytocin may be associated
      with an increased risk of uterine rupture and should be used carefully after
      appropriate counseling (II-2B). 10. Medical induction of labor with prostaglandin
      E2 (dinoprostone) is associated with an increased risk of uterine rupture and
      should not be used except in rare circumstances and after appropriate counseling
      (II-2B). 11. Prostaglandin E1 (misoprostol) is associated with a high risk of
      uterine rupture and should not be used as part of a TOL after Caesarean section
      (II-2A). 12. A foley catheter may be safely used to ripen the cervix in a woman
      planning a TOL after Caesarean section (II-2A). 13. The available data suggest
      that a trial of labor in women with more than 1 previous Caesarean section is
      likely to be successful but is associated with a higher risk of uterine rupture
      (II-2B). 14. Multiple gestation is not a contraindication to TOL after Caesarean
      section (II-2B). 15. Diabetes mellitus is not a contraindication to TOL after
      Caesarean section (II-2B). 16. Suspected fetal macrosomia is not a
      contraindication to TOL after Caesarean section (II-2B). 17. Women delivering
      within 18-24 months of a Caesarean section should be counseled about an increased
      risk of uterine rupture in labor (II-2B). 18. Postdatism is not a
      contraindication to a TOL after Caesarean section (II-2B). 19. Every effort
      should be made to obtain the previous Caesarean section operative report to
      determine the type of uterine incision used. In situations where the scar is
      unknown, information concerning the circumstances of the previous delivery is
      helpful in determining the likelihood of a low transverse incision. If the
      likelihood of a lower transverse incision is high, a TOL after Caesarean section
      can be offered (II-2B). VALIDATION: These guidelines were approved by the
      Clinical Practice Obstetrics and Executive Committees of the Society of
      Obstetricians and Gynaecologists of Canada.

PMID- 16001463
TI  - Health savings accounts: wave of the future or flavor of the month?

PMID- 16001464
TI  - Significance of silver-stained nucleolar organizer regions in early diagnosis and
      prognosis of oral squamous cell carcinoma: a multivariate analysis.
AB  - Argyrophilic nucleolar organizer regions (AgNORs) appear to be of diagnostic and
      prognostic significance in different types of human tumour. The present study
      examined the AgNOR counts in normal, premalignant and malignant oral mucosa to
      evaluate their potential as a biological marker for tumour progression and a
      prognostic predictor for treatment outcome in oral carcinomas. The Spearmann's
      rank correlation analysis between AgNOR counts and various stages of tumour
      progression in oral mucosa exhibited a highly significant positive coefficient
      (r(s) = 0.7969; p < or = 0.001), thus indicating the role of AgNORs in the early
      diagnosis of potentially malignant oral leukoplakia. When analyzing the
      prognostic significance of AgNOR in oral carcinomas, mean count > 2.8 concurred
      with poor prognosis in both univariate and multivariate analysis. Along with
      AgNOR counts, the T-status of disease was also found to be an independent
      predictor for treatment outcome in multivariate analysis. Thus T3 and T4 tumours,
      with mean AgNOR counts more than 2.8, are aggressive and may exhibit resistance
      to current treatment protocols.

PMID- 16001466
TI  - Proceedings of the First Monolith Summer School. June 6-9, 2004. Portoroz,
      Slovenia.

PMID- 16001465
TI  - Pilomatrixoma: a diagnostic pitfall in fine-needle aspiration biopsies. A review
      from a small county hospital.

PMID- 16001467
TI  - The gift of oneself and the donation of organs.

PMID- 16001468
TI  - Medical ethics: an offspring of the church.

PMID- 16001469
TI  - When the shouting has to stop: America and abortion.

PMID- 16001470
TI  - Changing your genes.

PMID- 16001471
TI  - Rationing and the long-term-care system.
AB  - Rationing is a concept newly introduced in health-systems analysis in the United
      States. Although rationing, when applied to health care, is a fearful word to the
      elderly, at the most basic level it is simply a method that enables government to
      intervene in the private marketplace to allocate resources to achieve particular
      policy ends. This intervention to affect allocation of health care resources has
      long been used by all levels of government in the United States. Intervention by
      government in the private marketplace is examined as a means of expanding or
      limiting the supply of health care services or expanding or limiting the demand
      for such services. The Oregon rationing experiment with Medicaid services has
      significantly contributed to the introduction of the concept of rationing of
      health care. As expected, there is a disproportionate interest by the elderly in
      rationing health care; thus the effect of the Oregon rationing experiment on the
      elderly is discussed, as are other allocation interventions on long-term care, as
      a service of particular interest to the elderly.

PMID- 16001472
TI  - The doctor's ethics.

PMID- 16001473
TI  - Euthanasia, the ultimate abandonment.
AB  - In this issue we are pleased to publish the address given recently by Mrs Rita
      Marker of the Anti-euthanasia Task Force (USA) at a press conference in the House
      of Commons in London. It offers a most informative update on the development of
      euthanasia discussion in the United States. We must be grateful that the
      situation elsewhere is different. In Germany, as a recent correspondent told the
      Editor, the memory of euthanasia under the Nazis is still too fresh for there to
      be such a development. Even in Holland there are moves to develop a hospice
      programme, to offer a radically alternative approach to terminal care. Yet in
      Britain the idea of the living will is beginning to catch on, and we do well to
      take note of how it is being used in the United States as a gateway to
      euthanasia.

PMID- 16001474
TI  - Human fertilisation and embryology.

PMID- 16001475
TI  - Chapter 765 revisited: Florida's new advance directives law.

PMID- 16001476
TI  - Crime and the biotech revolution.

PMID- 16001477
TI  - In vitro fertilization through egg donation: a prospective view of legal issues.

PMID- 16001478
TI  - She's come for an abortion: what do you say?

PMID- 16001480
TI  - Circumpolar health research under the umbrella of the International Polar Year.

PMID- 16001481
TI  - Being a specialist GP.

PMID- 16001482
TI  - Ear syringing.

PMID- 16001484
TI  - [Easy ophthalmic pathology].

PMID- 16001483
TI  - [Easy ophthalmic pathology].

PMID- 16001485
TI  - Most Medicare outpatient visits are to physicians with limited clinical
      information technology.
AB  - This Data Bulletin uses linked data from two sources: the Centers for Medicare
      and Medicaid Services (CMS) 2001 5 Percent Carrier File, which contains complete
      claims for a representative sample of 5 percent of Medicare fee-for-service
      beneficiaries, and the 2001 Center for Studying Health System Change (HSC)
      Community Tracking Study (CTS) Physician Survey, a nationally representative
      survey of nearly 12,400 physicians. The linked sample includes claims for more
      than 506,000 Medicare outpatient visits to 8,641 CTS physicians. Estimates are
      weighted to be nationally representative of all Medicare fee-for-service
      physician outpatient visits in 2001. Use of the Medicare data is permitted under
      a data use agreement between Peter B. Bach, M.D., of Memorial Sloan-Kettering
      Cancer Center and CMS.

PMID- 16001486
TI  - A higher standard. Report tells Congress to let regulators strip tax-exempt
      status and go after boards that approve unreasonable executive pay.
AB  - It's time to give regulators the power to strip the tax-exempt status from
      charities that offer unreasonable executive compensation. That's the word from
      the Panel on the Nonprofit Sector's report to Congress. The report's 120
      recommendations come amid increasing scrutiny of not-for-profits, and a spokesman
      for Sen. Chuck Grassley, left, says the Iowa lawmaker hopes to introduce
      legislation on the matter soon.

PMID- 16001487
TI  - Old lessons learned. Longtime standards used to cut surgical infections.

PMID- 16001488
TI  - Healthcare inflation plateaus. Some had hoped growth rate would be falling.

PMID- 16001489
TI  - Near the top of the heap. Cohen ranks fifth in association compensation.

PMID- 16001490
TI  - Rehab fight may continue.

PMID- 16001491
TI  - Blues primed to pay. 29 plans are already paying for performance.

PMID- 16001492
TI  - AMA sets some ground rules. Detailed conditions outlined for pay-for-performance.

PMID- 16001493
TI  - A common goal. IT deals show 'harmonization' in healthcare.

PMID- 16001494
TI  - Stuck with the check? Guidant recall raises questions of medical tab.

PMID- 16001495
TI  - In a galaxy not so far away... AHERF lost its way. Will HealthSouth debacle
      awaken CFOs' inner Jedi?

PMID- 16001496
TI  - An accounting of benefits. To regain public trust, hospitals must document a
      range of community services.

PMID- 16001497
TI  - AHERF revisited. Pittsburgh, Philly markets continue recovery from the system's
      bankruptcy, but scars remain.

PMID- 16001498
TI  - Collateral damage. For CFOs, effects of AHERF have been more indirect.

PMID- 16001499
TI  - Competition, Texas-style. Ellis has grown East Texas Medical Center from a
      midsized hospital to one of the state's largest systems.

PMID- 16001500
TI  - A very precious gift of time. Alzheimer's patients, with no cure in sight, still
      benefit from an early diagnosis.

PMID- 16001501
TI  - Double trouble speak.

PMID- 16001502
TI  - Synthesis and enzymatic evaluation of modified acceptors of recombinant blood
      group A and B glycosyltransferases.
AB  - The disaccharide alpha-L-Fucp-(1 --> 2)-beta-D-Galp-(1 --> O)-Octyl (1) is an
      acceptor for the human blood group A and B glycosyltransferases. Seven analogues
      of 1, containing deoxy, methoxy and arabino modifications of the Fuc residue,
      were chemically synthesized and kinetically evaluated in radioactive enzymatic
      assays. Both the enzymes tolerate modification of the 3'-OH on the fucose
      residue. The 2'-OH was found to be key to the recognition of the acceptors by
      these enzymes. The arabino derivative was recognized as an acceptor by the A
      transferase (Km of 200 microM), but not the B transferase and is the first
      synthetic acceptor capable of distinguishing between the two enzyme activities.

PMID- 16001503
TI  - Syntheses of sugar-related trihydroxyazepanes from simple carbohydrates and their
      activities as reversible glycosidase inhibitors.
AB  - Five diastereomeric trideoxy-1,6-iminohexitols were synthesised, and their
      inhibitory activities were determined against selected glycosidases. For
      comparison, 1,4,5-trideoxy-1,5-imino-D-lyxo-hexitol, the 4-deoxy derivative of 1
      deoxymannojirimicin, was prepared by enzymatic isomerisation of 6-azido-3,6
      dideoxy-D-ribo-hexose into the corresponding 2-ulose and subsequent hydrogenation
      accompanied by intramolecular reductive amination.

PMID- 16001504
TI  - Isolation and identification of the intermediates during pyrazole formation of
      some carbohydrate hydrazone derivatives.
AB  - Reaction of the oxidation product of L-ascorbic acid, dehydro-L-ascorbic acid,
      with o-phenylenediamine, followed by 2,4,6-trichlorophenylhydrazine (3) afforded
      3-[1-(2,4,6-trichlorophenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin
      2(1H)one (4), whose structure was deduced from studying its periodate oxidation,
      which gave the glyoxal derivative 3-[1-(2,4,6-trichlorophenylhydrazono)glyoxal-1
      yl]quinoxalin-2(1H)one (5) that upon reduction afforded 3-[1-(2,4,6
      trichlorophenylhydrazono)-2-hydroxyethy-1-yl]quinoxalin-2(1H)one (6). The
      reaction of 5 with 3 afforded the bishydrazone 3-[1,2-bis(2,4,6
      trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1H)one. The reaction of 5 with
      acetic anhydride in pyridine afforded the 2,3-dihydrofuro[2,3-b]quinoxaline
      derivative 2-acetoxy-3-[2-acetyl-2-(2,4,6-trichlorophenyl)hydrazono)]-2,3
      dihydrofuro[2,3-b]quinoxaline. Acetylation of 4 with acetic anhydride in pyridine
      afforded the acyclic diacetate intermediate 3-[3,4-di-O-acetyl-2-deoxy-1-(2,4,6
      trichlorophenylhydra-zono)but-2-en-1-yl]quinoxalin-2(1H)one (12), which was also
      obtained from the reaction of 4 with boiling acetic anhydride. Compound 12
      rearranged under the reaction conditions to give the pyrazole derivatives 3-[5
      (ace-toxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1H)one (14)
      and 2-acetoxy-3-[5-(acetoxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3
      yl)]quinoxaline (15), as well as the 2,3-dihydrofuro[2,3-b]quinoxaline derivative
      2-(2-acetoxyethen-2-yl)-3-[2-(2,4,6-trichlorophenyl)hydrazono]-2,3
      dihydrofuro[2,3-b]quinoxaline. Acetylation of 3-[5-(hydroxymethyl)-l-(2,4,6
      trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1H)one (16) with acetic anhydride in
      pyridine or 12 with boiling acetic anhydride afforded 15 and 16, respectively.
      Treatment of 4 with diluted sodium hydroxide afforded the pyrazolo[2,3
      b]quinoxaline (flavazole) derivative 1-(2,4,6-trichlorophenyl)-3-(L-threo
      glycerol-1-yl)pyrazolo[2,3-b]quinoxaline whose acetylation afforded the acetyl
      derivative 3-(2,3,4-tri-O-acetyl-L-threo-glycerol-1-yl)-1-(2,4,6
      trichlorophenyl)pyrazolo[2,3-b]quinoxaline. The assigned structures were based on
      spectral analysis. The activity of compound 4 against hepatitis B virus has been
      studied.

PMID- 16001505
TI  - Analysis of pigeon intestinal mucin allergens using a novel dot blot assay.
AB  - Many glycoproteins contain multiple glycosylation sites that can present multi
      valent epitopes for antigenic recognition. Release of the oligosaccharides
      results in loss of avidity of antibody binding, which has been overcome by
      reforming clustered ligands, usually by reductive amination of free reducing
      oligosaccharides to poly-amine groups. We have adapted this approach to
      hydrazinolytic release of O-linked chains of mucin glycoproteins and 'one-pot'
      microscale coupling to poly-L-lysine (PLL). The conjugated PLL adheres to
      nitrocellulose membranes through washing procedures required for antibody or
      lectin overlay and detection. We show evidence for the applicability of this
      technique using lectin and antibody reactivity to the oligosaccharides of pigeon
      intestinal mucins, which have been implicated in the allergic disease pigeon
      fanciers' lung.

PMID- 16001506
TI  - Determination of the solution conformation of D-gluco-dihydroacarbose, a high
      affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy.
AB  - The determination of the bound solution conformation of D-gluco-dihydroacarbose
      (GAC), a tight-binding inhibitor of several glycosidase and amylase enzymes, by
      glucoamylase is described. Transferred NOE NMR experiments and line-broadening
      effects indicate that GAC is bound in a conformation resembling that observed in
      the crystal structure. This contrasts with the predominant conformation of GAC
      when free in solution. The NMR results also suggest regions on the carbohydrate
      that are in close contact with the protein. The determination of the bound
      solution conformation of GAC by glucoamylase using transferred NOE (trNOE)
      measurements is a significant achievement given the high affinity constant (Ka =
      3 x 10(7) M(-1)) for this receptor-ligand pair. It is striking that the off-rate
      for complexation is still sufficiently high to permit observation of trNOEs.

PMID- 16001507
TI  - Molecular structures and hydrogen-bond networks in crystals of synthetic 1-D
      galactosamide bolaamphiphiles.
AB  - The crystal structures of synthetic 1-galactosamide bolaamphiphiles, N,N'
      bis(beta-D-galactopyranosyl)decane-1,10-dicarboxamide (1) and N,N'-bis(beta-D
      galactopyranosyl)dodecane-1,12-dicarboxamide (2), were determined by single
      crystal X-ray analysis. The space groups are P21, Z = 2 with cell dimensions: a =
      13.624(2), b = 4.832(3), c = 21.178(3) Angstroms, beta = 98.57(1) degrees for 1;
      a = 13.521(2), b = 4.838(1), c = 23.706(2) Angstroms, beta = 104.945(10) degrees
      for 2. The galactopyranosyl rings of 1 and 2 are in a 4C1 chair conformation. The
      bolaamphiphile molecules are arranged in a layered structure for 1 and 2, with
      the alkylene chains packed parallel all over the layers. The hydroxyl groups of
      the galactopyranosyl rings in 1 and 2 form identical three-dimensional hydrogen
      bond networks. The connecting decamethylene spacer of 1 has a kink conformation,
      while the dodecamethylene chain of 2 an all-trans zigzag conformation.

PMID- 16001509
TI  - [The 28th ICOH Congress on Occupational Health--Milan, 11-16 June 2006].

PMID- 16001508
TI  - Synthesis, control of substitution pattern and phase transitions of 2,3-di-O
      methylcellulose.
AB  - An improved heterogeneous procedure has been found for the regioselective
      introduction of trityl and 4-methoxytrityl groups at the primary positions of
      cellulose. The 6-O-tritylcelluloses produced were completely methylated by MeI
      NaOH in Me2SO solution. The trityl groups were then completely removed to afford
      2,3-di-O-methylcellulose without significant degradation of the polymer. 1H and
      13C NMR spectroscopy and degradation analysis showed less than 5% deviation from
      the regular substitution pattern. Under optimum reaction conditions, almost
      perfectly regular cellulose derivatives could be obtained. Small changes in the
      substitution pattern had a strong effect on the phase transitions of the O
      methylcelluloses in water. It was shown by DSC for the first time that perfect
      2,3-di-O-methylcellulose does not undergo phase separation at elevated
      temperatures.

PMID- 16001510
TI  - Allergic cutaneous diseases in hairdressers.
AB  - BACKGROUND: Hairdressers are commonly exposed to water, irritants, sensitizers,
      and are at risk of occupational skin diseases. Several cases of allergic contact
      dermatitis and contact urticaria in hairdressers have been described over the
      last few years. OBJECTIVES AND METHODS: The paper aims to report occupational
      agents which can induce allergic cutaneous diseases in hairdressers; moreover an
      analysis of the literature was carried out to review data concerning
      epidemiology, clinical evaluation, management and prevention. RESULTS AND
      CONCLUSIONS: Hairdressing carries a high risk of skin damage, especially for the
      hands. Allergic contact dermatitis is the most common disorder. Training
      represents a risk factor, while the role of atopy and nickel sensitivity as
      etiological agents is controversial. A great number of chemicals may induce
      allergic cutaneous diseases in hairdressers, such as nickel, thioglycolate, p
      phenylendiamine (and other dye-related substances), persulphates, quaternary
      ammonium compounds, protein hydrolysates, surfactants, cyanoacrylates, latex,
      rubber haptens and others. Avoidance of further contact with the identified
      causal sensitizer(s) is the most important measure for management and prevention;
      to this end, a number of specific preventive strategies should be implemented.

PMID- 16001511
TI  - [Myeloproliferative disorders due to the use of gasoline as a solvent: report of
      three cases].
AB  - BACKGROUND: Health effects of occupational exposure to benzene are currently a
      problem, despite the fact that preventive measures have been in existence in
      Italy for more than 40 years. OBJECTIVES: To describe three recent cases of
      severe haematological disease presumably induced by an occupational exposure to
      benzene. Exposure occurred as a result of contact with ordinary automobile petrol
      used as a solvent-degreaser for metal parts. METHODS: Clinical diagnosis was
      performed using standard immuno-phenotypic and morphological criteria; the
      hypothesis of an occupational origin was derived from analysis of the
      occupational histories. RESULTS: The first case was a 59 year-old blacksmith
      suffering from acute myeloid leukaemia (AML) FAB M2, who had used petrol for 36
      years to degrease the forged metal parts before painting them. The second was a
      53 year-old mechanic with AML FAB M3 who had used petrol for 15 years to degrease
      mechanical parts of tanker motors. The third was an 82 year-old car mechanic
      suffering from idiopathic myelofibrosis since the age of 75, who had used petrol
      to degrease mechanical car motor parts for 42 years. In all three cases, the
      environmental hygiene measures necessary to limit inhalation or skin contact were
      not followed and, at times, in the case of the two mechanics, the petrol was
      siphoned by mouth; so there was substantial exposure to the 1-5% benzene present
      in the petrol. Latency of the disease was between 30-50 years from start of
      exposure, and between 3-17 years following cessation of exposure. CONCLUSION: The
      cases described indicate that the myelotoxic effects of benzene are still a
      problem. They were the consequence of improper use of petrol, due to total
      misinformation of the risks involved in such use. It is not possible to ascertain
      whether the cases presented are a casual aggregation or if the use of petrol as a
      solvent is more common than is normally believed; in the latter case two
      questions must be asked: is a "normal" occupational history able to discover such
      an uncommon risky condition of exposure? If it cannot, how many cases of benzene
      related diseases escape aetiological diagnosis? It is not possible to provide
      precise answers but efforts should be made to improve the quality of information
      about the risks of petrol. Furthermore, in all cases of haematological disease
      potentially related to benzene, any form of contact with petrol, even if
      uncommon, should be carefully researched.

PMID- 16001512
TI  - Lead poisoning caused by Indian ethnic remedies in Italy.
AB  - BACKGROUND: Complementary or alternative medicine has become widespread in
      Western Countries and since the remedies are "natural" they are believed to be
      free of toxic effects and health risks. Ethnic remedies may contain lead, other
      metals and toxic substances. OBJECTIVES: To show how lead poisoning as a result
      of using ethnic remedies may be severe enough to cause serious damage to health,
      and to increase awareness among family doctors and occupational physicians of the
      risks associated with ethnic remedies. METHODS AND RESULTS: Description of ethnic
      remedy-related lead poisoning in 2 native Italian adults, with clinical,
      laboratory and toxicological data. CONCLUSIONS: When metal poisoning is
      diagnosed, ethnic remedies should be included among the putative sources so as to
      avoid erroneous attribution to workplace exposure and application of unneeded
      preventive measures.

PMID- 16001513
TI  - [Occupational brucellosis in slaughtering of sheep and goats: study of five cases
      from a municipal abattoir in south-eastern Sicily].
AB  - BACKGROUND: Brucellosis is a world-wild zoonosis of bacterial origin. In Italy,
      where reporting of the disease is mandatory, the incidence is 2.1 cases every
      100,000 inhabitants, but tends to be higher in southern regions. However, the
      incidence decreased from 1999 to 2002. CASES: Five cases of occupational
      brucellosis, four slaughter-house operators and one veterinary surgeon, were
      reported in a slaughter-house in south-eastern Sicily employing 15 people.
      RESULTS: A study of the slaughtering process for sheep and goats led to
      identification of 23 different operations, some of which involved greater
      probability of infection: animal consignment; unloading and leading animals from
      the stable to the trap; strangling and bleeding; skinning and removal of mammary
      glands; removal and processing of abdominal viscera; post-mortem examination;
      mobile equipment and facility maintenance, and washing/disinfection. All affected
      workers had participated in one or more of these operations. CONCLUSION:
      Eradication of brucellosis in stock-farms should lead to the disappearance of the
      human disease, since the two are closely related. Despite legislation aimed at
      eradicating brucellosis in cattle, which has been in force since 1992, the
      prevalence of the human disease has risen in Italy, especially in Sicily. Within
      the framework of prevention, occupational physicians should exercise specific
      surveillance of brucellosis risk by carefully examining the plasma antibody
      content of workers involved in the slaughtering process. Occupational health
      physicians should also provide ad hoc information regarding the infectious agent
      and modes of transmission during slaughtering operations as well as specific
      training in the use of protective equipment, which is the only way of providing
      protecting from contagion by infected animals.

PMID- 16001514
TI  - Occupation and lung cancer risk in Leningrad Province, Russia.
AB  - To investigate the association between occupation and lung cancer risk in
      Leningrad Province, Russia, we identified 540 pathologically diagnosed lung
      cancer cases (474 males and 66 females) and 582 controls (453 males and 129
      females) from the 1993-1998 autopsy records of the 88 state hospitals of the
      Province. Lifetime occupational histories were obtained from personal records
      coded according to the standard Russian occupational classification system. Lung
      cancer risk was increased in workers in the manufacturing industry, particularly
      in the food industry and wholesale/retail trade and in the miscellaneous
      manufacturing industry. An increased risk was also found in subjects employed in
      chemical and metal production for 10 years or more. When we considered the
      association between specific occupations and lung cancer, waste incineration
      operators and loaders exhibited an excess risk that increased with employment
      duration. The present study, which is the first to evaluate the risk of lung
      cancer by occupation in Russia, suggests the presence in Leningrad Province of
      exposure in the workplace to lung carcinogens that require further
      characterization to develop targeted and effective preventive measures.

PMID- 16001515
TI  - [Adverse reaction following suspected inhalation of nickel tetracarbonyl: case
      report].
AB  - BACKGROUND: Nickel tetracarbonyl (Ni(CO)4) is a highly toxic chemical that is
      produced as an intermediate compound in the Mond process of nickel refining.
      Occupational poisoning due to Ni(CO)4 is not frequent, and up to now about 300
      cases have been reported in the medical literature worldwide. OBJECT: A clinical
      case is reported of an industrial worker who developed clinical symptoms of
      respiratory distress probably due to accidental exposure to Ni(CO), METHODS:
      Clinical examination, chest X-ray data, history of exposure to nickel in the
      presence of carbon monoxide (CO) from a production plant that was located close
      to the reactor containing nickel, led to diagnosis of respiratory distress due
      occupational poisoning. RESULTS: Patient history, clinical symptoms that were
      characteristic of Ni(CO)4 poisoning: mild transient initial symptoms followed
      within 24 hours by more severe life-threatening events environmental data,
      history of exposure to nickel near a carbon monoxide (CO) production plant that
      was located close to the nickel containing reactor, indicated a putative causal
      relationship between diagnosis and exposure to nickel tetracarbonyl. CONCLUSIONS:
      The accident that without adequate respiratory therapy might have had fatal
      consequences, could have been avoided if the rules of technical and procedural
      prevention had been carefully observed.

PMID- 16001516
TI  - Increased risk for coronary heart disease in blue-collar workers at a military
      industrial plant in Greece?
AB  - OBJECTIVE: To test the hypothesis that blue-collar workers have a higher
      prevalence of risk factors for Coronary Heart Disease than white-collar workers.
      METHODS: A cross-sectional study of 262 employees (208 males, 54 females, mean
      age: 50,65 years) was made of a Greek military industrial plant. Blood samples
      were taken and analyzed for lipids, lipoprotein levels and glucose levels;
      arterial blood pressure and body mass index (BMI) were also recorded. Smoking
      habits were ascertained by the use of a self-administered questionnaire. RESULTS:
      White-collar workers had significantly higher mean levels of total and LDL
      cholesterol than blue-collar workers. No significant differences were found
      regarding arterial blood pressure, BMI, glucose, triglycerides and HDL
      cholesterol levels. Both groups reported similarly high rates of smoking.
      Multivariate analysis confirmed an independent association of abnormal levels of
      total and LDL cholesterol with white-collar occupation. CONCLUSION: These
      findings partly contradict the current pattern of CHD risk factors in Western
      workforces. Possible interpretations, as well as the limitations of the study,
      are discussed.

PMID- 16001517
TI  - A long-lasting pandemic: diseases caused by dust containing silica: Italy within
      the international context.
AB  - Diseases caused by dust containing silica represent an exemplary case study in
      the field of work-related diseases and in the history of the discovery of chronic
      industrial disease and its relationship to industrial society. Both dust and
      steam are indissolubly linked to the Industrial Revolution which everywhere was
      expected to replace slaves with masses of proletarians alike lesser gods. The
      identification of different nosological entities of dust-related diseases, the
      discovery that the most harmful dust particles in gold mines were invisible,
      insurance compensation and the development of the silicosis threshold limit value
      were all subjects of intense political negotiation that accompanied, with the
      connivance of doctors and scientists, a compromise between the health of workers
      and the economic health of industry. The preference for damage compensation
      (insurance system) over risk prevention (industrial hygienic measures) was also
      asserted and maintained in post-war Italy. Decline and modification of silicosis
      in Italy proceeded at the same rate as the introduction and subsequent
      application of more effective preventative legislation, especially with the
      protest movements of the working class at the end of the 1960s, together with the
      elimination of entire sectors of industrial activities, first those specialising
      in extraction and then the metallurgy.

PMID- 16001519
TI  - [BCG vaccination against tuberculosis in the health system].

PMID- 16001518
TI  - [Pleural malignant mesothelioma in a barber: a case of atypical and indirect
      professional exposure to asbestos].

PMID- 16001520
TI  - [National Convention: education and information on prevention and building safety
      -Bergamo, 22 November 2004].

PMID- 16001521
TI  - ["Healthy" nutrition--what are the facts, what are myths?].

PMID- 16001522
TI  - [Prevention of tumors through nutrition? "Fruit and vegetables instead of vitamin
      preparations" (interview by C. Straach)].

PMID- 16001523
TI  - [When the autonomic nervous system plays crazy. What is the origin of syncope?].

PMID- 16001524
TI  - [COPD with concomitant cardiac disease. Which cardiac medicine can he tolerate?].

PMID- 16001525
TI  - [Acupuncture study of national health insurance technicians. Blinded too early!].

PMID- 16001526
TI  - [Did the physicians involved in the study actually have a solid educated in
      acupuncture? This reader is doubtful].

PMID- 16001527
TI  - [Decubitus wounds: a neglected problem. What really prevents decubitus ulcer?
      (interview by Friederike Klein)].

PMID- 16001528
TI  - [Therapeutic outcomes in systemic lymphatic diseases and plasmacytoma. New hope
      for palliative patients].

PMID- 16001529
TI  - [Enlarged lymph nodes--rapid diagnosis of infectious and neoplastic causes].
AB  - Although lymphadenopathy is usually an expression of a harmless, self-limiting
      immune reaction, it may nevertheless also signify the presence of a malignant
      tumor or relevant infectious disease--in particular when the swelling is
      sizeable, rapidly progressive, and associated symptoms are present. If, however,
      unfavorable criteria are definitely absent (Table 1), a wait-and-see policy with
      re-evaluation in three to four weeks may initially be adopted.

PMID- 16001530
TI  - [Lymphomas: new therapeutic options].
AB  - Malignant lymphomas are differentiated clinically, morphologically and molecular
      biologically, into aggressive (formerly high-grade malignant) and indolent
      (formerly low-grade malignant) lymphomas. In the meantime, virtually all patients
      can be diagnosed and treated on an ambulatory basis. The introduction of the
      monoclonal antibody rituximab (R) in combination with chemotherapeutic agents,
      has led to the development of highly potent forms of chemoimmunotherapy. In the
      case of aggressive lymphomas, R-CHOP has been shown to be significantly superior
      to CHOP alone, both in elderly and younger patients. In stage III and IV indolent
      (follicular) lymphomas, rituximab/chemotherapy combinations achieve response
      rates in excess of 90%, and prolonged progression-free survival rates which, for
      the first time hold out hope of a cure. Monoclonal antibodies that can be coupled
      to radioisotopes open up new possibilities for potent radioimmunotherapy which
      look promising for effecting a cure or long-lasting palliation in additional
      proportion of the patients.

PMID- 16001531
TI  - [Monoclonal gammopathy--multiple myeloma].
AB  - The diagnosis of monoclonal gammopathy of undetermined significance (MGUS),
      requires both the detection of monoclonal gammopathy by immunofixation on the one
      hand, and the exclusion of signs of multiple myeloma (MM) on the other. The risk
      of an MGUS evolving into an MM is about 1% per year. The possibility of an MM
      should be considered in particular in elderly patients with an elevated ESR,
      anemia, recurrent infections and hypercalcemia. The diagnosis of MM is
      established on the basis of a constellation of major and minor criteria that
      includes characteristic results of serum and urine electrophoresis and
      immunofixation, routine lab and bone marrow (plasma cell infiltration) studies as
      well as complications (anemia, renal failure, hypercalcemia, osteolysis).
      Standard chemotherapy comprises melphalan-prednisone or chemotherapy VAD.
      Improved results have been achieved with high-dose chemotherapy plus various
      forms of stem cell transplantation. To treat recurrences, thalidomide and
      bortezomib are now available.

PMID- 16001532
TI  - [Incarcerated spontaneous intercostal hernia of the lung: a case report].

PMID- 16001533
TI  - [Does the use of metoprolol-succinate in patients with chronic heart failure lead
      to a higher efficacy in treatment without causing additional costs?].

PMID- 16001534
TI  - [Criticism of physician assistant unavoidable? But please not directly after tax
      revelation].

PMID- 16001536
TI  - [Some have taken a picture.... ...and won a digital camera].

PMID- 16001535
TI  - [Changing textbook of medical progress].

PMID- 16001537
TI  - [CME radiology 8].

PMID- 16001538
TI  - [What is your diagnosis? Erythema elevatum et diutinum].

PMID- 16001539
TI  - [Knowledge, attitudes and practices among travellers to tropical and subtropical
      countries].
AB  - Passengers with destinations in developing countries have been interviewed prior
      to departure on Zurich Airport. A total of 946 questionnaires were evaluated, 337
      on travel related malaria prior to visiting an endemic country, 609 on
      vaccinations. This corresponds to a response rate of 72.3%. Among the respondents
      550 (58.1%) had received travel health advice by a doctor. Overall, 25.5% were
      immunized against hepatitis A. While 70.4% of those who had obtained travel
      health advice carried medication against malaria, only 31.3% of those without
      such advice did so. Travel health advice resulted in a significantly increased
      appreciation of the risk of hepatitis A or malaria at the destination.
      Considerations on healthy travel should become a cornerstone in travel planning;
      special risk groups have been identified.

PMID- 16001540
TI  - [Aripiprazole in the treatment of schizophrenia].

PMID- 16001541
TI  - [Nasal polyps and osteolyses].
AB  - A 38-year-old man presented with a 2-month history of progressive leg pain. An x
      ray film of both tibial bones showed multiple osteolysis. At the same time, nasal
      polyps were present. A biopsy of the tibial bone remained unclear. A carcinoma
      was not found. A biopsy of the nasal polyps revealed a Rosai-Dorfman-Destombes
      disease.

PMID- 16001542
TI  - [St. John's Wort, corticosteroids, cocaine, alcohol ... and a first manic
      episode].
AB  - We describe an alcohol and cocaine abusing female patient who developed a first
      manic episode in the context of a corticosteroid prescription. The differential
      diagnoses are discussed on the basis of the available literature on secondary
      manias.

PMID- 16001543
TI  - [Halitosis of unknown origin. 44-year-old with very slender habitus, intermittent
      nausea and halitosis].

PMID- 16001544
TI  - [Exercise intolerance].

PMID- 16001545
TI  - Application of matrix solid-phase dispersion in the analysis of priority
      polycyclic aromatic hydrocarbons in fish samples.
AB  - The performance of matrix solid-phase dispersion (MSPD) for the extraction of
      polycyclic aromatic hydrocarbons (PAHs) in fish tissue is described. The
      suitability of different solid supports was tested as well as the influence on
      the extraction efficiency of the natural fat content in samples. Under optimal
      conditions 0.6-0.8 g of tissue sample, are dispersed with 2 g of
      octadecylsiloxane (C18) and 0.5 g of anhydrous sodium sulphate and transferred to
      the top of a polyethylene solid-phase extraction cartridge which already contains
      2 g of florisil and 1 g of C18. Cartridges were eluted with acetonitrile. The
      analysis of the extracts was carried out by high-performance liquid
      chromatography (HPLC) coupled with fluorescence detection. The proposed method
      provides detection limits between 0.04 and 0.32 ng/g for the different considered
      PAHs, below the maximum levels established by the some regulatory bodies for the
      six PAHs after recent oil spill episodes and European Union regulations.
      Recoveries over 80% were obtained for all compounds. Accuracy validation was
      carried out using the US National Institute of Standards and Technology (NIST)
      SRM 2977 reference material.

PMID- 16001546
TI  - A practical approach to transferring linear gradient elution methods.
AB  - Attempts to theoretically address the problems involved in transferring linear
      gradient elution methods have been somewhat ad hoc due to the simplifying
      assumptions usually made in conventional gradient elution theory. Until now, all
      equations based on the k* parameter of linear gradient elution theory used as the
      basis for predicting the separation selectivity have not explicitly included the
      effect of the dwell volume (VD). Using an exact equation for predicting k*, that
      is, one which fully accounts in an a priori fashion for VD, we find a set of
      simple yet exact equations which unequivocally must be satisfied to transfer an
      optimized linear gradient elution method from one system (column or instrument or
      both) to another. These relationships absolutely mandate that a change in the
      instrument dwell volume requires a proportional change in the column volume; in
      turn, a change in the column volume requires a proportional change in the flow
      rate and/or gradient time to maintain a constant gradient steepness. Although we
      are not the first to suggest these guidelines, this work provides a complete
      theoretical foundation for these exact guidelines for the maintenance of gradient
      selectivity for the case of transferring a linear gradient elution method between
      different columns packed with the same particles and/or between different
      instruments.

PMID- 16001547
TI  - Determination of total ribonucleotide pool in plant materials by high-pH anion
      exchange high-performance liquid chromatography following extraction with
      potassium hydroxide.
AB  - A new, improved method that only requires a potassium hydroxide extraction
      procedure is presented for the analysis of a full nucleotide pool in plant
      materials. Quantification was performed by high-pH anion-exchange chromatography
      (HPAEC) with UV detection after a potassium hydroxide extraction, and allowed the
      quantification of 13 linear ribonucleotides in a single run. The method has been
      validated by comparison of six extraction methods and also by measurement of the
      intracellular nucleotide levels of three plant species (cell cultures and
      leaves). The evolution of the nucleotide pool of Nicotiana tabacum cell culture
      during growth has also been measured, and showed an increase in the pool until
      the fifth day, where the growth rate reaches a maximum, after which a decrease
      was observed.

PMID- 16001548
TI  - Determination of acrylamide and methacrylamide by normal phase high performance
      liquid chromatography and UV detection.
AB  - A method using normal phase high performance liquid chromatography (NP-HPLC) with
      UV detection was developed for the analysis of acrylamide and methacrylamide. The
      method relies on the chromatographic separation of these analytes on a polar HPLC
      column designed for the separation of organic acids. Identification of acrylamide
      and methacrylamide is approached dually, that is directly in their protonated
      forms and as their hydrolysis products acrylic and methacrylic acid respectively,
      for confirmation. Detection and quantification is performed at 200 nm. The method
      is simple allowing for clear resolution of the target peaks from any interfering
      substances. Detection limits of 10 microg L(-1) were obtained for both analytes
      with the inter- and intra-day RSD for standard analysis lying below 1.0%. Use of
      acetonitrile in the elution solvent lowers detection limits and retention times,
      without impairing resolution of peaks. The method was applied for the
      determination of acrylamide and methacrylamide in spiked food samples without
      native acrylamide yielding recoveries between 95 and 103%. Finally, commercial
      samples of french and roasted fries, cookies, cocoa and coffee were analyzed to
      assess applicability of the method towards acrylamide, giving results similar
      with those reported in the literature.

PMID- 16001550
TI  - Variations of particle size and bed voidage distributions in expanded bed during
      transient operation processes.
AB  - Changes in bed expansion are frequently encountered during an expanded bed
      adsorption, such as during the initial bed expansion, feed loading and washing
      processes. We have here studied the changes of local particle size distribution
      and bed voidage of an expanded bed in the initial bed expansion process as well
      as those during the changes in mobile phase viscosity, which imitated feed
      loading and column washing processes. Using a glass column modified with three
      side sampling ports and Streamline AC as the solid phase, experimental
      measurements on a series of operation moments during the transient processes were
      carried out by sampling the particles from within the column at different axial
      positions. In the initial bed expansion process, the gradual formation of an
      axial classification from a settled bed to a stable expanded bed was first
      displayed. By changing the mobile phase from water to 10% (w/w) glycerol solution
      or vice versa, the variations in both the particle size distribution and bed
      voidage corresponding to the increase or decrease of the bed height caused by the
      changes of the mobile phase viscosity were examined as well. The transient
      changes of the local particle size distribution and bed voidage first occurred in
      the bed bottom and then progressed from bottom to top along the axial direction.
      However, the changes of bed voidage at different axial positions were not
      unidirectional. That is, by changing the mobile phase to the high-viscosity
      glycerol solution, a constant increase of the bed voidage was observed in the bed
      bottom, while a distinct decrease of the bed voidage before its increase was
      involved at the middle and top positions. This is ascribed to the compression
      effect caused by the upward movement of the lower part particles.

PMID- 16001549
TI  - Analysis of sialyl oligosaccharides by high-performance liquid chromatography
      electrospray ionisation-mass spectrometry with differentiation of alpha2-3 and
      alpha2-6 sialyl linkages.
AB  - A method for analysing sialyl oligosaccharides from bovine colostrum using high
      performance liquid chromatography-electrospray ionisation-mass spectrometry (HPLC
      ESI-MS) is described. Under positive ionisation mode, mass spectra of alpha2-3
      and alpha2-6 linkages were different, and the former produced a prominent B2 (or
      B3 in disialyl lactose) mass fragment. This fragment was absent from mass spectra
      with alpha2-6 linkages. Two sialyl oligosaccharides, which have not been reported
      previously, were tentatively identified. One comprises a N-acetyl neuraminic acid
      (Neu5Ac), two hexoses (Hex), and one N-acetyl hexosamine (HexNAc) residue
      ((Neu5Ac)1 (Hex)2 (HexNAc)1), and the other comprises one Neu5Ac and one Hex
      residue ((Neu5Ac)1(Hex)1).

PMID- 16001551
TI  - Analysis of semicarbazide in baby food by liquid chromatography tandem mass
      spectrometry (LC-MS-MS)--in-house method validation.
AB  - A method for detection of semicarbazide (SEM) in baby food was validated. SEM was
      extracted with hydrochloric acid and derivatised with 2-nitrobenzaldehyde, using
      [15N2,13C] semicarbazide as internal standard. The extract was neutralised,
      purified on a solid phase extraction cartridge and SEM was determined by reversed
      phase LC-MS-MS. Linearity was demonstrated in the ranges from 0.1 ng ml(-1) to 1
      ng ml(-1) and from 2 ng ml(-1) to 80 ng ml(-1). Matrix effects were non
      significant for meat-based and significant for apple and rice-based baby foods,
      in both ranges. Mean recoveries ranged from 87.8% to 107.2% with relative
      standard deviation from 0.2% to 9.1%, considering both ranges. Limits of
      detection and quantification were 0.1 microg kg(-1) and 0.25 microg kg(-1),
      respectively. The results of the validation process demonstrated the method
      suitability for use in food control.

PMID- 16001552
TI  - Effect of temperature on the chromatographic retention of ionizable compounds.
      II. Acetonitrile-water mobile phases.
AB  - The retentive behavior of weak acids and bases in reversed-phase liquid
      chromatography (RPLC) upon changes in column temperature has been theoretically
      and experimentally studied. The study focuses on examining the temperature
      dependence of the retention of various solutes at eluent pH close to their
      corresponding pKa values, and on the indirect role exerted by the buffer
      ionization equilibria on retention and selectivity. Retention factors of several
      ionizable compounds in a typical octadecylsilica column and using buffer
      solutions dissolved in 30% (v/v) acetonitrile as eluent at five temperatures in
      the range from 25 to 50 degrees C were carefully measured. Six buffer solutions
      were prepared from judiciously chosen conjugated pairs of different chemical
      nature. Their pKa values in this acetonitrile-water composition and within the
      range of 15-50 degrees C were determined potentiometrically. These compounds
      exhibit very different standard ionization enthalpies within this temperature
      range. Thus, whenever they are used to control mobile phase pH, the column
      temperature determines their final pH. Predictive equations of retention that
      take into account the temperature effect on both the transfer and the ionization
      processes are evaluated. This study demonstrates the significant role that the
      selected buffer would have on retention and selectivity in RPLC at temperatures
      higher than 25 degrees C, particularly for solutes that coelute.

PMID- 16001553
TI  - Characterisation of proanthocyanidin aglycones and glycosides from rose hips by
      high-performance liquid chromatography-mass spectrometry, and their rapid
      quantification together with vitamin C.
AB  - Fifteen individual proanthocyanidin aglycones and 19 glycosides, together with a
      complex mixture of chromatographically non-separated tetra- to octameric
      proanthocyanidin glycosides were detected--the non-separated glycosides being
      novel natural products--and characterised from dog rose hips using high
      performance liquid chromatography-electrospray ionisation mass spectrometry (HPLC
      ESI-MS). Along with these phenolics, a 50% aqueous ethanol extract of rose hips
      was found to contain high levels of Vitamin C. A simple and rapid HPLC method
      assisted by diode array detection for the estimation of the total concentration
      of proanthocyanidin aglycones and glycosides, as well as Vitamin C, in rose hip
      extracts was developed.

PMID- 16001554
TI  - Improved analysis of volatile halogenated hydrocarbons in water by purge-and-trap
      with gas chromatography and mass spectrometric detection.
AB  - An analytical system composed of a purge-and-trap injection system coupled to gas
      chromatography with mass spectrometric detection (PTI-GC-MS) specific for the
      analysis of volatile chlorinated hydrocarbons (VCHCs) (chloroform; 1,1,1
      trichloroethane; tetrachloromethane; 1,1,2-trichloroethylene;
      tetrachloroethylene) and trihalomethanes (THMs) (chloroform;
      bromodichloromethane; dibromochloromethane; bromoform) in water was optimised.
      Samples were purged and trapped in a cold trap (-100 degrees C) fed with liquid
      nitrogen (cryo-concentration). In order to make this method suitable also for
      only slightly contaminated waters, some modifications were made to PTI sample
      introduction, in order to avoid any air intake into the system. PTI, GC and MS
      conditions were optimised for halogenated compound analysis and limits of
      detection (LOD) were evaluated. The proposed method allows analysis of samples
      whose concentrations range from microg/L to ng/L. It is, therefore, applicable to
      drinking waters, in analyses required by law, and to slightly contaminated
      aqueous matrices, such as those found in remote areas, in environmental
      monitoring. Moreover, by changing cold trap temperature, even sparkling mineral
      waters can be analysed, thus avoiding CO2 interference during the cryo
      concentration phase. Our method has been successfully used on real samples: tap
      water, mineral water and Antarctic snow.

PMID- 16001555
TI  - Separation of eight selected flavan-3-ols on cellulose thin-layer chromatographic
      plates.
AB  - The potential of microcristaline cellulose as sorbent in the separation of eight
      compounds: (+)-catechin (C), (-)-epicatechin (EC), (-)-gallocatechin (GC), (-)
      epigallocatechin (EGC), (-)-epicatechin gallate (ECg), (-)-epigallocatechin
      gallate (EGCg), procyanidin B1 and procyanidin B2 was studied. Cellulose HPTLC
      plates prewashed in water (not necessary, when water was used as developing
      solvent) and dried with a hair dryer, bandwise application and development in
      horizontal developing chamber (sandwich configuration) gave the best results.
      Detection was performed using vanillin-H3PO4 reagent. Four new developing solvent
      systems were proposed: water, 1-propanol-water (20:80, v/v), 1-propanol-water
      acetic acid (4:2:1, v/v) and 1-propanol-water-acetic acid (20:80:1, v/v), and at
      least two of them were needed for the differentiation between all eight
      compounds. Surprisingly, water enabled the separation of epimers C from EC and GC
      from EGC, as well as the dimers procianidin B1 and B2. Additionally, C, EGC, B1
      and B2 were separated from all the other compounds. The best choice for
      developing solvent is given for each of the studied compounds. The best
      separation of the five main catechins (EC, GC, EGC, ECg, EGCg) present in green
      tea extract was achieved using 1-propanol-water-acetic acid (20:80:1, v/v). The
      chromatograms of oak bark extract developed in solvents with higher water content
      (1-propanol-water (1:4, v/v) and 1-propanol-water-acetic acid (20:80:1, v/v))
      showed less bands than chromatograms developed in solvents with higher organic
      modifier content (e.g. 1-propanol-water-acetic acid (4:2:1, v/v)). It was proved
      that such behavior was due to the presence of procyanidins beside the main
      component catechin.

PMID- 16001556
TI  - Experimental determination and calculation of distribution coefficients between
      air and fiber with polydimethylsiloxane coating for some groups of organic
      compounds.
AB  - This paper reports the results of experimental determination of distribution
      coefficients K(fa) for five terpene hydrocarbons and five aliphatic ketones
      between air and polydimethylsiloxane (PDMS) coating for solid-phase
      microextraction. To estimate the values of K(fa) for compounds of the same
      classes, which did not undergo experiments, it is proposed to use an empirical
      two-parameter equation in which various physicochemical and structural
      characteristics weakly correlated with each other are used as descriptors. It is
      also shown that for these purposes it is possible to use distribution
      coefficients of compounds in any other two-phase heterogeneous system, e.g.
      octanol-water or hexane-acetonitrile. This approach was applied to estimate K(fa)
      values of 92 volatile organic compounds.

PMID- 16001557
TI  - High-performance thin layer chromatography method for quantitative determination
      of four major anthraquinone derivatives in Rheum emodi.
AB  - A high-performance thin layer chromatographic (HPTLC) method for the rapid and
      simple quantification of the four major anthraquinone derivatives i.e. physcion,
      chrysophanol, emodin and chrysophanol glycoside in Rheum emodi is described.
      HPTLC of anthraquinone derivatives was performed on pre-coated RP-18 F254S HPTLC
      plates. For achieving good separation, the mobile phase of methanol-water-formic
      acid (80:19:1, v/v/v) was used. The densitometric determination of anthraquinone
      derivatives was carried out at 445 nm in reflection/absorption mode. The
      calibration curves were linear in the range of 20-100 ng for physcion, 80-400 ng
      for chrysophanol and emodin, and 200-1000 ng for chrysophanol glycoside. The
      method was found to be reproducible and convenient for quantitative analysis of
      anthraquinone derivatives in the methanolic extract of rhizomes of R. emodi
      collected from three different locations of Western Himalaya, India.

PMID- 16001558
TI  - [The General Health Directorate publishes its five-year health promotion
      programme].

PMID- 16001560
TI  - [Validation of a screening test of language and learning disorders for 6-year old
      children (ERTLA6)--a prospective study].
AB  - Medical practitioners are, like the other health, education and childhood
      professionals, important actors of the language and learning disorders'
      screening. Six years old--the age at which children start the elementary school-
      is a key age for this screening. At the request of practitioners, a
      multidisciplinary staff had developed a screening tool: ERTLA6 (Epreuves de
      reperage des troubles du langage et des apprentissages de l'enfant de 6 ans). The
      objective was to validate the capacity of ERTLA6 to predict the school
      performance. A sample of 187 children was randomly constituted among the whole
      population of last year nursery school children in an area of France (the
      Academie de Nancy-Metz). Those children, aged from 5 to 6, were screened with
      ERTLA6 by the school practitioner during a medical visit (score from 0 [the best]
      to 18 [the worse]). The School outcomes (considered as judgment criteria) were
      assessed 2 or 3 years later, after two years of elementary school. 148 children
      had completed their follow-up (the others: 27 moving house, 6 absents the day of
      evaluation, 2 missing data). Mean age was 5; 10 years. With a threshold > or = 7,
      ERTLA6 sensibility and specificity were respectively 79% [63-94] and 87% [81-93];
      the positive predictive value was 58% [42-74], the negative predictive value was
      95% [90-99]. The percentage of well classified children was 84% [69-99]. To our
      knowledge, ERTLA6 is the first validated tool in France for screening language
      and learning disorders which can be used by practitioners for the prediction of
      school outcomes.

PMID- 16001559
TI  - [Self-evaluation of the quality of life of children aged 6 to 12 years old:
      construction and first steps in the validation of kidlQol, a generic computer
      based tool].
AB  - The KidlQol is a self-evaluation computer-based instrument to assess the quality
      of life of children aged 6 to 12 years old. This self-evaluation comprises three
      areas of their subjective quality of life: physical, psychological and social. A
      computer-assisted tool, composed of 62 items, was developed and set up based upon
      the results from the evaluation of the initial prototype tool which underwent a
      series validation steps, tested among children with and without psychological
      problems. This evaluation lead to the production of a final tool called KidlQuol,
      which is composed of 44 items. This tool, which utilises computer images to
      represent real-life situations, is adapted for and accessible to children with a
      French cultural background aged between 6 and 12 years old. As a generic tool, it
      could be used among a population of children with various types of handicaps,
      chronic diseases or psycho-social difficulties.

PMID- 16001561
TI  - [Tropical ecopathology: up hill and down dale Buruli ulcer].
AB  - Buruli ulcer (Mycobacterium ulcerans) sees its incidence increase particularly in
      West Africa. Our Non Governmental Organization (Projet Humanitaire Afrique Nord
      Sud) studied the distribution of cutaneous ulcer (of which Buruli ulcer) between
      a flooded site (Bonou) and a dry site (Ketou) in Benin. The ratio "prevalence of
      Buruli ulcer in our patients of Bonou on prevalence of Buruli ulcer in our
      patients of Ketou" was 7.5 with a confidence interval at 95% at [1.4 - 41.4].
      There is a link between a watery ecosystem and the emergence of Buruli ulcer.
      Buruli ulcer is overrepresented in the under 15 age group. It can interest all
      the zones of the tegument whereas the other ulcers concern especially the lower
      limbs. Thus doctors could not be unaware of the importance of ecological factors
      ... in precarious medium where diagnosis is based on interrogation, clinical
      examination and field experience.

PMID- 16001562
TI  - [Young people's perceptions of tobacco-related cancer].
AB  - An anthropological study was conducted on the island of Reunion between March and
      September 2004 within the framework of a project called "The non-smoking
      generation" carried out by the Regional Committee for Health Education. The
      primary objective was to provide field workers with a basis for reflection which
      they could incorporate into their tobacco prevention activities aimed at young
      people. The perceptions of youth on tobacco-use related cancer were explored
      using a sample population group of 37 young people aged between 14 and 25 years
      old (girls and boys, smokers and non-smokers, those who attend school and those
      who don't) from across the island. Interviews were conducted using an
      anthropological analysis grid and completed through observational sessions in
      their homes, schools and neighborhoods. The results, set within the context of
      time and the places where tobacco is consumed, demonstrate that their
      relationship to cigarettes symbolises some of the inherent characteristics of
      adolescence, namely, the difficulty in finding and establishing one's own limits,
      in integrating oneself into society and in envisioning one's potential future. An
      interesting observation was also made regarding their views on the one hand of a
      paradoxical approach relating the development of cancer and tobacco consumption
      behaviour, and the real, concrete physical and psychological impact of the
      disease on the other. The young people often expressed a certain fatality and a
      feeling of control ("I can quit whenever I want to!"). The team also found within
      their remarks a sense of being unfortunate as opposed to that of being in
      control, coupled with fear as opposed to feeling invincible ("cancer only happens
      to other people"). Finally, the study has allowed for reflections on youth
      tobacco prevention interventions to be nurtured with respect to how individual
      young people position the consequences of tobacco use and smoking, mainly with
      regard to their own personal responsibility.

PMID- 16001563
TI  - [HIV/AIDS prevention in the school setting: practices of biology teachers in
      France and in the Congo].
AB  - HIV and AIDS prevention is part of the biology class curriculum in junior high
      and high school in both France and the Congo. The teachers must not only present
      the scientific knowledge but also try to incite and convince the students to
      adopt certain preventive behaviours in terms of their own personal conduct. This
      places the teachers in the domain of having a health promotion and education
      role. How do teachers perceive this new role? What objectives and outcome
      measures have they set, and what kind of educational method do they intend to use
      to achieve them? Based on interviews conducted in the year 2000 of 25 teachers
      (12 in France and 13 in Congo-Brazzaville), a profile has been defined for each
      teacher based on an analysis of his/her responses with regard to their role in
      terms of health education and more specifically in relation to AIDS prevention. A
      number of questions and concems emerged from this exercise, some of which were
      shared in common and others were clearly country-specific.

PMID- 16001564
TI  - [The medical records of home health care patients: a complement or alternative to
      an electronic file?].
AB  - Home health care services for dependant people involve participation and
      interventions of professionals from the health care, medico-social and social
      sectors. In order to ensure quality care, the flow of information must
      appropriately circulate between all of the various care providers. The
      establishment of an electronic medical file for these patients is a possible
      solution which has been proposed to be conducted in next years. A paper medical
      record is the property of the patient and offers the possibility of an
      alternative and complementary solution. The electronic file would use the
      existing available file as a starting point, and without any additional
      organisational structures being implicated, it allows for better coordination of
      the health, medical and social activities. An experimental implementation of this
      in the Franch-Comte region of France demonstrated the advantages and benefits of
      such a tool based on a logic centered upon the individual and the open sharing of
      practices between professionals in the medical and social sectors.

PMID- 16001565
TI  - [Medical emergency care units in France].
AB  - The objective of this article is to take inventory of the different medical
      emergency care units in France as of June 30, 2003, and to describe their main
      characteristics. METHODOLOGY: A telephone survey was conducted which posed
      questions based on a standard questionnaire to the Regional Unions of Liberal
      Doctors, the County Advisory Boards of the Medical Orders, and the directors and
      managers of the existing emergency care units. RESULTS: 97 medical safe houses
      were inventoried, 46 of which were operational and 51 which were in development.
      The Ile-de-France region is the region with the highest concentration of these
      units either operating or under construction. A large majority of the emergency
      care units were created since the year 2000, and half of them are located within
      health care centres and the other half into separate cells either close or
      distant from existing health care centres. More than half of them have no other
      staff aside from doctors, whilst the others comprise a spectrum of personnel
      including secretaries, nurses, and social assistants amongst others. More than
      half of the doctors are paid at the cost of each consultation and per treatment
      and do not have a technical platform at their disposal. Usually, these emergency
      care units are open all night during the week and on the weekends. One-third of
      them collaborate with the emergency centre and ambulance service (those who
      respond to calls to 15) and three-quarters of them are funded by the city's
      Assistance Fund for the Quality of Care. CONCLUSION: It would seem advantageous
      that a Charter for operation and management of these establishments be drafted
      and implemented in order standardise these types of structures and that their
      supervisors implement a national and regional follow-up mechanism for the
      establishments in order to better evaluate the evolution in terms of health care
      organisation, in particular with respect to raising the level and capacity of
      response.

PMID- 16001566
TI  - [An inter-university diploma on tobacco and smoking cessation: pedagogical
      evaluation and professional impact].
AB  - The aim of the post-graduate degree course on tobacco and smoking cessation is to
      train professionals who have dedicated themselves to the fight against tobacco
      and smoking. An educational assessment of the degree programme was carried out in
      order to evaluate its impact on practice. A questionnaire was mailed to 60
      students registered in the programme at Strasbourg University between 1997 and
      2002 (with a response rate of 71.6%). The evaluation was able to shed light on
      the strengths and weaknesses of the teaching in the programme and the level of
      student satisfaction. The tobacco control and smoking cessation interventions of
      the students before and after completing the course were compared in order to
      assess the impact on their professional practice. The programme's participants
      came from a variety of professions including medical doctors (74.4%), paramedical
      staff (16.3%) and other professions (6.9%). The students acknowledged the
      course's high level of quality (the teachers were appreciated, and the programme
      was comprehensive). The structure of the course was operational; however, the
      students admitted that they felt that the practical application and the
      interactive aspects of the learning (such as case studies, role playing, training
      in a specific smoking cessation intervention were insufficient. They also noted a
      lack of emphasis on treatments that do not rely on pharmacotherapy such as
      behavioural therapy and psychological support. Tobacco cessation related problems
      or side effects of quitting like weight gain, anxiety or insomnia were not
      appropriately developed. The majority of students were very satisfied with the
      theoretical basis of the curriculum and with their internship in a tobacco
      cessation consultation intervention. Today, 69% of the students trained are
      working in smoking cessation and tobacco control. They have been able to
      diversify their activities, going from prevention to tobacco cessation, and vice
      versa. Course tracks focusing on pregnant women, adolescents and behavioural
      therapies have now been introduced into the degree programme. In terms of further
      investing in the improvement of skills and competencies, the programme could
      better respond to the students' needs by taking into account the development of
      interactive teaching methods such as role playing and workshops.

PMID- 16001567
TI  - [Dental consultations at a university hospital in Toulouse: the role for
      conservative treatments in oral health].
AB  - A retrospective study was carried out looking at the files of 481 patients who
      were seen for their first consultation at a university hospital dental school
      clinic. Their needs for conservative treatment were evaluated and the data from
      their files were analysed, including the following elements: demography, general
      health status, the expressed reason for the consultation, and the initially
      planned treatment. The descriptive analysis reveals a relatively young population
      group with an average age of 43.8 years, for whom 32% of them had existing or
      past medical conditions which necessitated that certain precautions be taken when
      prescribing conservative treatment. The most frequently given reasons for the
      consultation were the need for an annual dental check-up (41%) and pain (20%).
      74% of the patients were in need of conservative treatments, and a priority for
      an initial treatment was cited for 48.4% of them.

PMID- 16001568
TI  - [Evaluation of a university hospital unit specialising in treating adults at risk
      of suicide].
AB  - In France, suicide prevention has been a public health priority since 1992. Half
      of all suicide attempts are repeated attempts made by people who have already
      tried to commit suicide, and the risk of death increases by 1% after the first
      attempt. Today, hospitalisation has become an unavoidable consequence for those
      who have attempted suicide, and recommendations for best practice were recently
      issued in France (1998). The objective of this study was two-fold: 1) to assess
      the quality of management and care provided for patients hospitalised in a
      university hospital in Angers after having attempted suicide, an evaluation that
      was based in part on the criteria of the National Agency on Health Accreditation
      and Evaluation (ANAES); and 2) the demonstrate the value and high utility of such
      a unit specialising in caring for patients recovering from attempted suicide. The
      unit has now been in existence for over 5 years, and has treated 42% of such
      patients who require hospitalisation. One investigator was responsible for asking
      251 patients (on the day of their release) who had been hospitalised anytime
      during the given 6 month period (November 2002 - May 2003) to complete a
      questionnaire containing approximately 100 items. In order to be eligible for the
      study, patients had to be older than 16 years and hospitalised for at least 48
      hours. 155 questionnaires were completed (62%), and there were 96 patients were
      notable to participate on the day of their release. Nine of the 14 criteria
      recommended by the ANAES were met in over 65% of the cases, and three in less
      than 40%. Following the analysis of the data through logic regression, it
      remained clear that unit specialising in the care of people who have attempted
      suicide was better able and equipped to meet the standards of the ANAES'
      recommendations than a standard hospital medical unit. Visits with a psychiatrist
      or psychiatric nurse occurred more frequently in the specialised unit (p < 0.04),
      interviews with the patients' family members were more frequent (p < 0.01), the
      confidentiality of the discussions from the interviews was more often respected
      and maintained (p < 0001), and the information provided by the caregivers and
      staff was more effective in the specialised unit (p < 0.03). One of the main
      benefits and results of these aforementioned differences is that the patients in
      the suicide unit more often perceived a distinct improvement in their depression
      (p < 0.007). All of these arguments indicate that hospitalisation in a special
      unit provides real benefits to patients, and the results of this study advocate
      strongly in favour of increasing the capacity of the unit, which is currently
      limited to only 6 beds.

PMID- 16001569
TI  - [The use of data from the literature on nutritional education projects: a
      qualitative study].
AB  - The study is based on the observation that data from the existing literature is
      underutilised during the project development stage. The objective is to carry out
      a study to track the current status quo on how the knowledge from the literature
      is used and incorporated. Semi-structured interviews of professionals working in
      nutritional education of youth were conducted to assess this aspect in the French
      speaking community in Belgium. The study permitted the identification of which
      types of data are being used by the respondents, as well as which elements can
      have a positive or negative impact their incorporation. Moreover, it was observed
      that most of the field workers who participated in the study would prefer to have
      access to more data relevant to their local context than data on a specific
      topic. The study highlighted the need for more training to be provided to the
      nutritional educators working in the field, in particular in the areas of
      information needs and their interpretation of these needs in light of the data
      available.

PMID- 16001570
TI  - [Frequency of dementia and pre-dementia in elderly people requesting an Autonomy
      Adapted Assistance grant in the department of Nievre].
AB  - This study was carried out in the French county of Nievre after the establishment
      of a new state funded grant for elderly people called the Autonomy Adapted
      Allocation. The study looks at the medical evaluations conducted in the homes of
      elderly people aged 60 and over who have submitted a request for this new grant
      (a total of 2388 requests were received). The study points to a high level of
      dependence within the target population of those who are "susceptible to
      dementia". It also demonstrated that the current scale used for identifying those
      who are susceptible to dementia is insufficient for its purpose in this case, and
      unfortunately it lacks the ability to include a portion of the population who
      should be considered as recipients of these funds. This gap corroborates the
      difficulty in fully appreciating and understanding the functional repercussions
      of dementia.

PMID- 16001571
TI  - [Correlating nursing with basic nursing philosophy concepts].

PMID- 16001572
TI  - [Living autonomously at home despite handicap].

PMID- 16001573
TI  - [Challenges on all fronts].

PMID- 16001574
TI  - [How research finds its way into general practice].

PMID- 16001575
TI  - [There is no way around assessment].

PMID- 16001576
TI  - [Tailored for the individual needs].

PMID- 16001577
TI  - ["If we are convinced, we can achieve many things" (interview by Margrit Bachl)].

PMID- 16001578
TI  - ["Cafi Momo" instead of drugs].

PMID- 16001579
TI  - [Advancement through criticism].

PMID- 16001580
TI  - [Identity, our most important possession].

PMID- 16001581
TI  - [Handicap: the right to choose one's own life style].

PMID- 16001582
TI  - [Understanding the past to build the future].

PMID- 16001583
TI  - [When the time for reconciliation comes].

PMID- 16001584
TI  - [Nurses, misunderstood and still indispensible].

PMID- 16001586
TI  - [Obstacle in choice].

PMID- 16001585
TI  - [A ray of sunshine].

PMID- 16001588
TI  - [Freedom to participate].

PMID- 16001587
TI  - ["If you had seen the feet"!].

PMID- 16001589
TI  - Medical and physical readiness of the U.S. Army Reserve for Noble Eagle/Enduring
      Freedom/Iraqi Freedom: recommendations for future mobilizations.
AB  - The U.S. Army Reserve plays an important role in the war-fighting capabilities of
      the U.S. military. There have been concerns, however, regarding the health and
      physical readiness of this force. Recently Army Reservists were mobilized for
      Operation Noble Eagle/Iraqi Freedom. We report on both the medical waivers
      requested and issues related to soldiers found medically nonavailable for
      deployment on data collected and analyzed from several mobilization sites. Four
      hundred thirty-one medical waivers were requested. Of 60,000 mobilized,
      approximately 2.7% were found to be medically nonavailable for deployment,
      predominately enlisted and male. The most common problems identified were
      orthopedic, psychiatric, diabetes, asthma, obstetrical-gynecological, and
      cardiac. The overall prevalence of medically nonavailable for deployment of Army
      Reservists was low. Most of the conditions leading to nondeployable troops were
      attributable to chronic disease. Interventions to decrease the level of medically
      nonavailable for deployment and to lessen mobilization site operations are being
      implemented.

PMID- 16001590
TI  - The 274th Forward Surgical Team experience during Operation Enduring Freedom.
AB  - The 274th Forward Surgical Team (FST) was deployed in support of Operation
      Enduring Freedom from October 14, 2001 to May 8, 2002. During this period, the
      FST was asked to perform many nondoctrinal missions. The FST was tasked with
      functioning as a mini-combat support hospital during the earlier phases of
      Operation Enduring Freedom, performing in-flight surgical procedures and
      resuscitation of combat wounded, conducting split operations with surgical
      coverage of both Karshi and Khanabad, Uzbekistan, and Bagram, Afghanistan, and
      leading the multinational medical coalition assembled for Operation Anaconda and
      other combat operations staged from Bagram. Overall, the 274th FST took care of
      approximately 90% of U.S. combat casualties during this period and treated a
      total of 221 combat casualties. The FST treated 103 total surgical cases,
      including 73 with combat wounds. At the time, this experience with combat
      casualties and the surgical care of combat wounds was the largest since the
      Persian Gulf War. More importantly, this account describes the flow, frequency,
      and type of combat casualties seen in a low-intensity conflict like that being
      waged currently in Afghanistan. It is hoped that this depiction will aid in the
      preparation, equipping, and overall utilization of surgical assets in similar
      future conflicts.

PMID- 16001591
TI  - Treatment of urinary calculi in the combat zone.
AB  - Renal colic is a common condition among deployed soldiers in the Middle East.
      Eight percent of all admissions to the jump package of the 21st Combat Support
      Hospital in Mosul, Iraq, during Operation Iraqi Freedom involved patients with
      renal colic and urinary stones. The majority of patients were treated
      successfully with primary care measures. Fourteen percent of patients required
      urologic interventions; however, many of these soldiers were treated with
      ureteral stents and returned to duty. Aggressive management of urolithiasis
      resulted in 92% of soldiers remaining in the combat zone, preserving the fighting
      strength of supported units.

PMID- 16001592
TI  - Combat casualties in Afghanistan cared for by a single Forward Surgical Team
      during the initial phases of Operation Enduring Freedom.
AB  - BACKGROUND: The 274th Forward Surgical Team (FST) was the first FST deployed to
      Bagram, Afghanistan, to provide surgical care for combat casualties during the
      initial phases of Operation Enduring Freedom. This is an analysis of the
      distribution, cause, and severity of wounds for combat casualties and the
      surgical procedures they required. METHODS: A prospective database was maintained
      for combat casualties cared for by the 274th FST. The database included
      demographic data, vital status, mechanism of injury, distribution and severity of
      wounds, and surgical care provided. RESULTS: The FST cared for 224 combat
      casualties, including 153 U.S. soldiers, 19 coalition soldiers, 32 Afghan militia
      forces soldiers, and 20 detainees. Fragments were the most common mechanism of
      injury (49%), and the extremity was the most common location of injury (58%),
      whereas gunshot wounds were the most common cause of death (57%). There were few
      significant head, chest, or abdominal wounds (13%). The FST treated 103 surgical
      cases (73 with combat wounds), including neurosurgical, thoracic, general,
      orthopedic, and vascular cases, with a total of 180 procedures. CONCLUSIONS: The
      distribution, cause, and severity of wounds were similar to those in the Persian
      Gulf War, despite the obvious differences between these conflicts. The use of
      modern technologies, such as compact, portable, ultrasound and digital X-ray
      systems, expanded the capabilities of the FST. Even low-intensity conflicts can
      produce significant numbers of combat casualties, and the FST must be manned,
      trained, equipped, and supplied to treat a wide variety of combat wounds.

PMID- 16001593
TI  - Combat casualty care: the Alpha Surgical Company experience during Operation
      Iraqi Freedom.
AB  - BACKGROUND: Operation Iraqi Freedom was the first large-scale combat operation
      involving the U.S. Marine Corps since the Persian Gulf War in 1991. Data from a
      combat surgical company are presented. METHODS: Records of all U.S. and Iraqi
      combat casualties admitted to the surgical company were reviewed. RESULTS: Fifty
      three (57%) of 93 patients suffered penetrating injuries. Most wounds were
      produced by high-explosive munitions (mines, hand grenades, and rocket-propelled
      grenades), and the majority (51%) of wounds were to the extremities. The time to
      surgical care averaged 4.7 hours (range, 1.5-48 hours), and 98% of the patients
      seen at our facility survived. CONCLUSIONS: The time from injury to surgical care
      was considered long by civilian standards; however, this did not appear to affect
      outcomes substantially. A small percentage (5.2%) of injuries were to the torso.
      Hypothermia was commonly present. Because of the nature of their wounds, all
      patients required additional surgery after evacuation to rear area facilities.
      The outcomes of individual patients are not known, although it is known that only
      one Marine died after reaching medical care and, to date, no Marines have
      subsequently died of their wounds.

PMID- 16001594
TI  - A humanitarian mission in southern Iraq: utilization of the 7th Field Hospital of
      the Army of the Czech Republic--a report on its medical activities and working
      conditions.
AB  - Between April 24 and September 18, 2003, a total of 7,099 outpatient treatments
      were performed. Between June 3 and September 18, 2003, a total of 124 patients
      were surgically treated and 209 patients were hospitalized; the hospital recorded
      1,239 bed-days, 137 of them in the intensive care unit. A total of 924 X-ray and
      ultrasound examinations were performed, as well as 10,014 laboratory tests. Local
      inhabitants accounted for 90.5% of the patients. In their practice, the doctors
      encountered a very wide spectrum of surgical and nonsurgical diagnoses. Part of
      the work was to support humanitarian activities, with supplies of humanitarian
      material, selection of children for specialized cardiosurgical treatment in the
      Czech Republic, and blood donations. Work in that unstable region was
      significantly complicated by the extreme climate and the high security risk.

PMID- 16001595
TI  - Anesthesia services aboard USNS COMFORT (T-AH-20) during Operation Iraqi Freedom.
AB  - USNS COMFORT (T-AH-20), the only U.S. hospital ship to be deployed in support of
      combat operations during Operation Iraqi Freedom, sailed from Baltimore,
      Maryland, on January 6, 2003, and returned on June 12, 2003. During the course of
      her deployment, 648 anesthetic procedures were performed. We describe the
      anesthesia services provided, lessons learned, and recommendations for future
      concepts of employment.

PMID- 16001596
TI  - Anger in the combat zone.
AB  - A U.S. Army Reserve Combat Stress Control prevention team was dispatched to
      Afghanistan in support of Operation Enduring Freedom to provide preventative
      mental health care to a U.S. Army airborne division and Special Operations
      forces. The team's mission was to ensure mental health readiness of units in the
      area of operations. In Bagram, Afghanistan, the Combat Stress Control team
      identified anger as a very prevalent emotion in the combat zone. Anger management
      interventions with individual and group counseling were implemented to help
      soldiers cope with anger. Of 7,000 military personnel stationed there during the
      team's rotation, there was not one completed suicide or homicide. This article
      describes how the 113th Medical Company identified, treated, and controlled anger
      at Bagram Airbase, Afghanistan, between June 20, 2002, and December 20, 2002,
      with anger management interventions. This article does not address the
      psychophysiological features of anger.

PMID- 16001597
TI  - Pathogenesis and management of a late manifestation of vivax malaria after
      deployment to Afghanistan: conclusions for NATO Armed Forces Medical Services.
AB  - Because of the worldwide engagement of the German armed forces, tropical diseases
      may come to the attention of their medical services. In particular, acquired
      malarial infections, which sometimes become symptomatic only months or even years
      after soldiers return from military operations, need to be addressed. Other
      forces, such as the British, U.S., Australian, and Italian armed forces, reported
      cases of vivax malaria up to approximately 20 months after soldiers returned from
      military operations. The importance of a sound history and rapid diagnosis,
      leading to appropriate treatment, is emphasized in this case report of a 27-year
      old German soldier who reported for sick call in his unit complaining of a flu
      like illness, which later proved to be vivax malaria. The special parasitological
      features of Plasmodium vivax infection are discussed.

PMID- 16001598
TI  - Knowledge, attitudes, and practices regarding epidemiology and management of
      travelers' diarrhea: a survey of front-line providers in Iraq and Afghanistan.
AB  - To evaluate the relationship between medical knowledge and clinical practice, a
      survey on travelers' diarrhea was administered to military health care providers
      attending a professional development and trauma management conference. The survey
      was administered at the beginning of the conference and 58 of the 76 attendees
      participated by completing a questionnaire. Respondents were aware of the
      standard definition of travelers' diarrhea; however, their knowledge about the
      epidemiology and management of travelers' diarrhea was low. Less than one-third
      correctly answered questions on etiology and more than two-thirds made incorrect
      management choices in treatment of mild to moderate watery diarrhea and
      dysentery. Important knowledge gaps about gastroenteritis were identified and
      should serve as a basis to develop military-specific clinical guidelines and
      training programs.

PMID- 16001599
TI  - Survey of repellent use by service members arriving in Kuwait for Operation Iraqi
      Freedom 2.
AB  - The 8th Medical Brigade, deployed to Kuwait in January 2004 in support of
      Operation Iraqi Freedom provided theater-wide health service support and medical
      command and control. An historic "surge" of troops and equipment occurred during
      our deployment as 140,000 service members (SMs) redeployed out of theater and
      110,000 arrived to take their place. The brigade's preventive medicine personnel
      conducted a questionnaire-based survey at military camps in northwestern Kuwait
      in mid-March to determine whether SMs had been provided with supplies and
      information to protect them against endemic vector-borne diseases. Of 1,200
      questionnaires distributed, 870 (73%) were returned. In addition to military
      affiliation information, the survey contained specific questions related to the
      provision of n-diethyl-m-toluamide repellents, permethrin and treated uniforms,
      and medical threat briefings. On average, less than one-half of the SMs received
      these resources before their arrival in Kuwait. Significant differences of
      resource provision existed among service branches, components, and mobilization
      or deployment stations.

PMID- 16001600
TI  - Medical problems of detainees after the conclusion of major ground combat during
      Operation Iraqi Freedom.
AB  - After the conclusion of major ground combat operations during Operation Iraqi
      Freedom, the focus of the mission changed, although intense armed conflict
      continued. Included in this mission was management of security detainees,
      including provision of their medical care. We retrospectively reviewed the
      admission records identified at a short-term holding facility over 2 months and
      diagnoses of detainees admitted to a combat support hospital over 4 months as a
      health care service utilization statistics review. Six thousand six hundred
      thirty-one detainee encounters occurred at the short-term facility with
      approximately 45% of detainees reporting medical problems during each daily
      evaluation. Most frequent complaints were neurological (11%), gastrointestinal
      (10%), and respiratory (8%). Two hundred nineteen detainees' admission diagnoses
      were retrospectively reviewed from the combat support hospital, 98 (45%) due to
      gunshot or fragmentary injuries and 121 (55%) to other medical problems. Medical
      problems included cardiac (29%), gastrointestinal (17%), neurological (14%),
      musculoskeletal (11%), and pulmonary (6%) disease. Medical problems not
      traditionally dealt with in a combat theater, including management of transplant
      recipients, patients with cardiac valve replacement, and cancer patient, were
      also seen.

PMID- 16001601
TI  - The dynamics and ethics of triage: rationing care in hard times.
AB  - Triage of medical care, whether necessary because of routine daily limitations or
      forced by exceptional circumstances, such as for soldiers injured in combat or
      civilians in mass casualty situations, is increasingly coming under scrutiny. The
      decisions that limit access to fundamental and even life-or-death treatments are
      fraught with controversy. These decisions are difficult for the medical provider
      to make and are even more difficult for the patient to understand. Medical
      providers are poorly trained to address the numerous factors involved in triage
      decisions under the pressure of limited time. Patients are understandably selfish
      and short-sighted regarding their own care. Both provider and patient can feel
      that triage is immoral. In contrast, when triage is taught proactively and
      reviewed relative to the situation, the ethical principles that guide triage are
      evident and intact. Both provider and patient must learn the considerations and
      consequences of triage.

PMID- 16001602
TI  - Malignant hyperthermia susceptibility and the trauma patient.
AB  - Assorted casualties are expected from combat. Triage of the wounded may result in
      some going directly to surgery. Although every minute is essential, anesthetic
      care of these trauma patients must adhere to all established standards of care. A
      timely preoperative assessment must include identifying the patient's risk for
      malignant hyperthermia (MH). If a patient is found to be malignant hyperthermia
      susceptible, all appropriate measures must be taken to provide the patient with a
      safe anesthetic. In the forward, austere military environment, anesthesia
      providers may experience logistical and manpower constraints when administering
      anesthesia. In this setting, it may be more even more crucial for preoperative
      recognition of MH and when this is not possible, focus must shift to
      perioperative detection and early treatment. The following case report emphasizes
      the importance of preoperative recognition and having an established MH protocol
      and access to dantrolene.

PMID- 16001603
TI  - Clinical case series: the use of Prazosin for combat-related recurrent nightmares
      among Operation Iraqi Freedom combat veterans.
AB  - OBJECTIVE: Increased central nervous system norepinephrine outflow and alpha1
      adrenergic receptor responsiveness appear to be involved in the pathophysiologic
      processes of trauma-related nightmares in post-traumatic stress disorder. On the
      basis of reports that the brain-accessible alpha1-adrenergic antagonist Prazosin
      substantially reduced chronic combat-related nightmares among Vietnam War
      veterans, we evaluated Prazosin effects on combat-related nightmares among combat
      soldiers returning from Operation Iraqi Freedom. METHODS: Twenty-eight soldiers
      who self-reported distressing combat trauma-related nightmares on a
      postdeployment questionnaire were prescribed low-dose Prazosin before bedtime.
      RESULTS: Of the 23 soldiers for whom follow-up evaluations were available, 20
      experienced marked improvement (complete elimination of nightmares), 2
      experienced moderate improvement (reduced nightmare frequency or intensity), and
      1 experienced no change. Prazosin was well tolerated. CONCLUSIONS: Prazosin
      appeared highly beneficial for combat-related nightmares characteristic of post
      traumatic stress disorder among troops recently returned from Operation Iraqi
      Freedom. These findings provide a rationale for a placebo-controlled trial to
      establish efficacy in this population.

PMID- 16001604
TI  - Spectrum of care provided at an echelon II Medical Unit during Operation Iraqi
      Freedom.
AB  - We describe the types of medical problems encountered at a U.S. Army echelon II
      medical facility during Operation Iraqi Freedom in the period after completion of
      major ground combat operations, a time of nation restructuring and intermittent,
      intense, armed conflict. A total of 4,831 patients were assessed between October
      1, 2003 and June 30, 2004, 74% with disease and nonbattle injury presentations,
      19% with dental complaints, and 7% wounded in action (WIA). Disease and nonbattle
      injury evaluations were predominantly musculoskeletal. Improvised explosive
      devices or mortars caused 78% of the WIA casualties. The most frequent dental
      evaluations were for restorations (47%). Thirty-eight individuals were admitted
      to holding beds, most commonly to receive intravenous antibiotic treatment for
      cellulitis (29%). Three hundred forty-one individuals were evacuated, including
      150 WIA. Determining the types of casualties seen at forward echelons of medical
      care during different phases of conflict can aid medical planning and help
      predict the type of medical resources required.

PMID- 16001605
TI  - Aeromedical evacuations from Operation Iraqi Freedom: a descriptive study.
AB  - OBJECTIVE: To describe health patterns in evacuated military members during
      Operation Iraqi Freedom (OIF) and utilize demographic, diagnostic, and pre- and
      postdeployment health information to understand the utility of data collected for
      aeromedical evacuations. METHODS: We conducted a descriptive analysis of U.S.
      evacuees from 2003 using data from the U.S. Transportation Command's Regulating
      and Command & Control Evacuation System and the Defense Medical Surveillance
      System. RESULTS: The typical patient was an Army male under the age of 29
      requiring orthopedic or surgical care. Disease/nonbattle injuries were six times
      as common as battle injuries and 94% were classified as routine evacuees. Eighty
      six percent had health data available in the Defense Medical Surveillance System.
      Two thirds had pre- and/or postdeployment questionnaire data. CONCLUSIONS:
      Combining data sources increases our understanding of disease patterns in
      deployed troops. Targeted preventive interventions can then be implemented.
      Changes in the U.S. Transportation Command's Regulating and Command & Control
      Evacuation System database can improve its utility as an epidemiological tool.

PMID- 16001606
TI  - Instituting preventive health programs at a level I aid station in a combat
      environment.
AB  - Preventive medical services have become standard at fixed military medical
      facilities worldwide. Unfortunately, offering these same programs can prove
      difficult during military deployments, because of mission demands and at times
      limited medical resources. We present successful implementation of physical
      therapy and smoking cessation programs at a level I aid station supporting
      soldiers during Operation Iraqi Freedom.

PMID- 16001607
TI  - Reported stressors and health care needs of active duty Navy personnel during
      three phases of deployment in support of the war in Iraq.
AB  - Literature has generously documented the stress of military members and their
      families during deployments in noncombat periods. Deployment has been shown to
      increase the needs of family members for health care, both physical and
      psychological. The purpose of this study was to describe the health care needs
      and perceived stressors of active duty members deployed to Iraq during the
      predeployment, mid-deployment, and postdeployment phases. Active duty Navy
      service members deployed on three aircraft carriers during Operation Enduring
      Freedom and Operation Iraqi Freedom in 2002-2003 were randomly selected to
      participate in an anonymous study that evaluated member well-being, adaptation,
      coping, anxiety, stress, and health care needs during three phases of deployment.
      Data were obtained from 474 Navy members in predeployment, 445 in mid-deployment,
      and 276 in postdeployment. Logistic regression analyses indicated that many
      variables predicted extreme anxiety during deployment, including mid-deployment
      phase, age of under 25 years, being childless, nonattendance at church, being
      enlisted, zero- or one-deployment history; no high school education, and being
      currently in counseling. Active duty members in all phases of deployment had
      equally disturbing levels of anxiety. All phases reported suicidal ideation at
      alarming rates (2.4% in predeployment, 4.9% in mid-deployment, and 3% in
      postdeployment). This study sheds new light on the stressors and subsequent
      health care needs of active duty members on carriers during war and provides
      valuable information for the prevention of high-risk anxieties and subsequent
      health risks for all service members during similar deployments.

PMID- 16001608
TI  - Dental morbidity in United Kingdom Armed Forces, Iraq 2003.
AB  - The aim of this article was to review the dental morbidity experienced by U.K.
      Armed Forces serving in Iraq from deployment on Operation Telic in January 2003
      until the end of phase 1 on May 1, 2003. U.K. Armed Forces dental teams treated
      1800 emergency patients, including 135 prisoners of war. A total of 1523 of these
      were regular troops and 101 were reservists or Royal Fleet Auxiliary troops. This
      gave morbidity rates of 148 cases per 1,000 personnel per year for the Royal
      Navy/Royal Marines and 160 cases per 1,000 per year for the Army. Lost
      restorations and fractured teeth were by far the most common problems
      experienced, followed by pericoronitis, pulpitis, and periapical pathological
      conditions. Both the rates of morbidity and the types of problems experienced
      were very similar to those reported by other nations in previous conflicts.

PMID- 16001609
TI  - Dental risk assessment for military personnel.
AB  - In 2002, the U.K. Defence Dental Agency adopted a system of dental risk
      categories to replace the dental fitness categories detailed in NATO Standard
      Agreement 2466. Personnel were assessed as being at high, medium, or low risk of
      experiencing dental morbidity during the next year, and a target was set to have
      no less than 90% of personnel at low or medium risk. The Persian Gulf War in 2003
      provided an opportunity to validate the risk assessment of U.K. troops deployed
      to Iraq (Operation Telic), when their morbidity experience was compared with the
      assessments of their risk. Data capture on risk assessment was considerably
      restricted but, for those for whom the comparison was possible, the predictive
      value of risk assessment appeared to be poor. However, 50% of all troops who were
      recorded as having experienced serious morbidity had been categorized as high
      risk. The system requires refinement of diagnostic criteria to maintain the
      sensitivity of the diagnosis of high risk while reducing the high false-positive
      assessment rate.

PMID- 16001610
TI  - Protecting military convoys in Iraq: an examination of battle injuries sustained
      by a mechanized battalion during Operation Iraqi Freedom II.
AB  - Improvised explosive devices and mines pose a formidable threat to military
      convoys traveling in Iraq. This study evaluated battle injuries sustained by a
      mechanized battalion operating against this threat. The objective was to gain
      insight into injury profiles and prevention. In the period examined, 32 attacks
      injured 120 Marines, causing 188 injuries. Upper extremity and head injuries
      (70%) were common, whereas lower extremity injuries (11%) were rare (as expected,
      given the threat and the body areas exposed). Shoulder and axilla protectors may
      be beneficial, but lower arm and hand injuries remain difficult to combat. Ear
      injury was the most common single injury type (23%). Combat earplugs may reduce
      ear blast injuries. Eye injuries were uncommon (0.5%), likely because of
      ballistic eye protection. Injury to the torso (11%) was generally mild, because
      of body armor vests. The majority of wounds were minor, allowing > 80% of the
      injured Marines to return to duty.

PMID- 16001611
TI  - A 20-year-old active duty male soldier with tachycardia and palpitations during
      Operation Iraqi Freedom.
AB  - A 20-year-old active duty male presented with palpitations, tachycardia, and a
      nontender, diffusely enlarged thyroid. The differential diagnosis and appropriate
      management of this patient's symptoms and physical examination findings are
      reviewed. Various diagnostic modalities are highlighted and effective treatment
      strategies as well as their risks and benefits are discussed.

PMID- 16001612
TI  - Octreotide for palliative treatment of bleeding from unresectable gastric cancer.

PMID- 16001613
TI  - Expression pattern of telomerase reverse transcriptase in rectal carcinoma
      predicts tumor radiosensitivity, local recurrence and disease-free survival.
AB  - BACKGROUND/AIMS: Predictive indicators of radiosensitivity in rectal cancer are
      required in order to avoid unnecessary preoperative radiotherapy. Telomeres are
      specialized structures at the ends of chromosomes that protect against that such
      as irradiation. Lower telomerase activity has been reported to be related to
      radiosensitivity in vitro or vivo. The aim of this study was to examine the
      possible role of telomerase reverse transcriptase expression, which is correlated
      to telomerase activity, in determining tumor radiosensitivity, local recurrence,
      and disease-free survival in patients with rectal carcinomas. METHODOLOGY: We
      studied 96 cases with advanced rectal carcinoma. In preradiation biopsy specimens
      of tumor samples, the number of cells stained positive for telomerase reverse
      transcriptase protein was evaluated by immunohistochemistry. RESULTS: The
      expression pattern of telomerase reverse transcriptase protein correlated with
      tumor radiosensitivity (P=0.0007). All tumors that had a high percentage of
      telomerase reverse transcriptase positive cells were radioresistant. High
      telomerase reverse transcriptase expression pattern is a predictive marker for
      high local recurrence or poor survival in patients with rectal cancer (P=0.011,
      P=0.0005). Telomerase reverse transcriptase expression and histopathological
      grade were significant prognostic variables for disease-free survival in the
      multivariate analysis (P=0.0003, P=0.0091). CONCLUSIONS: Telomerase reverse
      transcriptase raises the predictive possibility of tumor radiosensitivity in
      rectal cancer. Telomerase reverse transcriptase might be a useful parameter for
      patient selection for preoperative radiotherapy in rectal carcinoma.

PMID- 16001614
TI  - Serum interleukin-6 and interleukin-10 in patients with acute pancreatitis:
      clinical implications.
AB  - BACKGROUND/AIMS: Cytokines are assumed to play an important role in the
      pathogenesis of acute pancreatitis, but little is actually known. In this study,
      we assessed changes in the serum levels of interleukin-6 (IL-6), a
      proinflammatory cytokine, and interleukin-10 (IL-10), an anti-inflammatory
      cytokine, in patients with acute pancreatitis. METHODOLOGY: Serum levels of IL-6
      and IL-10 were measured in 47 patients with acute pancreatitis and compared with
      their clinical and laboratory data. Changes of the serum levels of the two
      cytokines were studied in relation to the severity of acute pancreatitis. In
      addition, the changes of these cytokines after treatment of severe acute
      pancreatitis were assessed. RESULTS: 1) The serum IL-6 level showed a significant
      correlation with markers of the severity of acute pancreatitis, suggesting that
      IL-6 was a useful indicator of the severity of this disease. 2) The IL-10/IL-6
      ratio was significantly lower in patients with severe acute pancreatitis,
      suggesting that a proinflammatory response was predominant in these patients. 3)
      The IL-10/IL-6 ratio of the patients with severe acute pancreatitis was
      significantly increased after treatment, especially in patients who received
      continuous regional arterial infusion of a protease inhibitor and antibiotics.
      CONCLUSIONS: The predominant pathological state of patients with severe acute
      pancreatitis may be altered from the systemic inflammatory response syndrome to
      the compensatory anti-inflammatory response syndrome by successful treatment.

PMID- 16001616
TI  - Acute cholecystitis in the elderly.
AB  - BACKGROUND/AIMS: The population of Finland is ageing fast, and acute
      cholecystitis is common among elderly people. Because the treatment options have
      changed greatly since the late 1980's, we wanted to find out whether the active
      treatment policy nowadays used in our hospital has some effects on operability,
      morbidity, mortality and the duration of the in-patient period. The numerous
      serious illnesses of elderly people that cause considerable morbidity and
      mortality underlines the importance of risk stratification, and clinical
      variables were therefore also tested for their ability to predict the probability
      of morbidity and mortality. METHODOLOGY: Two hundred and eighteen patients aged
      over 75 years, 92 patients during the 5-year period 1988-1992 (Period I) and 126
      patients during the 5-year period 1998-2002 (Period II) had been admitted into
      our hospital for acute cholecystitis, and they were identified from a computer
      database. During these two periods, different treatment strategies were used. The
      clinical data were reviewed from the database and the patient records. RESULTS:
      The active use of ERCP and percutaneous cholecystostomy during Period II
      decreased the number of all operations and emergency operations. Only six of the
      43 patients who underwent early cholecystostomy were later scheduled for
      cholecystectomy. Postoperative morbidity did not differ between the two periods,
      and stepwise logistic regression analysis showed obesity to be an independent
      predictor of morbidity. Overall mortality was 8% during period I and 6% during
      period II, and of the clinical variables, underlying lung disease, malnutrition,
      pericholecystic fluid collection in ultrasound and perforation of the gallbladder
      were independent predictors of mortality in stepwise logistic regression
      analysis. Neither the primary in-patient period nor the total in-patient period
      were significantly shorter during Period II. CONCLUSIONS: Active treatment of
      acute cholecystitis in the elderly may decrease the need for emergency surgery.
      Malnutrition and perforation of the gallbladder are the most important predictors
      of mortality in this patient group.

PMID- 16001615
TI  - Prognostic significance of Ku70 protein expression in patients with advanced
      colorectal cancer.
AB  - BACKGROUND/AIMS: Ku protein stimulates DNA repair and signals the damage/stress
      responses, which may affect apoptosis and cell proliferation. The expression of
      Ku70 has been reported to be related to cell proliferation in a human gastric
      cancer cell line. However, in colorectal carcinoma, the clinical significance of
      Ku70 expression remains unclear. We examined the expression pattern of Ku70 in
      sporadic colorectal cancer and its relation to clinicopathological parameters and
      survival. METHODOLOGY: We studied 101 consecutive cases of advanced colorectal
      carcinoma. In resected specimens, the number of cells stained positive for Ku70
      protein was evaluated by immunohistochemistry. RESULTS: The percentage of cells
      expressing Ku70 in different tumors ranged from 4.2-99.7%. The elevated Ku70
      expression group comprised 52 of 101 cases (52%). No significant correlation was
      seen between Ku expression pattern and the clinical parameters except depth of
      invasion. pTNM stage, histopathological grade and Ku70 were significant variables
      for prognosis of survival in the multivariate analysis. CONCLUSIONS: This is the
      first report correlating reduced survival with elevated expression of Ku protein
      in colorectal adenocarcinoma. Ku may be a new prognostic marker useful for
      selecting adjuvant treatment strategies.

PMID- 16001617
TI  - Thermo-chemo-radiotherapy for advanced gallbladder carcinoma.
AB  - BACKGROUND/AIMS: Many gallbladder carcinomas are detected at an advanced stage,
      and the outcome of the patients with these tumors is dismal despite aggressive
      tumor removal. We have treated advanced gallbladder carcinoma with
      chemoradiotherapy combined with hyperthermia. In this study, clinical
      effectiveness of thermo-chemo-radiotherapy (TCRT) for advanced gallbladder
      carcinoma was evaluated in comparison with other treatment modalities.
      METHODOLOGY: Two hundred and seventy patients with advanced gallbladder carcinoma
      (Stage VI) were treated. According to treatments received, they were divided into
      five groups as follows: group 1; 30 patients treated with TCRT, group 2; 19
      patients underwent R0-resection, group 3; 39 patients underwent R1,2-resection,
      group 4; 57 patients treated with chemo- and/or radiotherapy, group 5; 125
      patients with only supportive therapy. RESULTS: In group 1, there were 19
      objective responses (5 complete response and 14 partial response) in respect to
      tumor regression, and 15 (6 complete response and 9 partial response) of 20
      patients with obstructed bile duct showed resolution of the bile duct. The
      survival rate was best in group 2. A significant improvement of long-term
      survival was exhibited in group 1 and 3 compared to group 4 and 5, and there was
      no significant difference between group 1 and 3 (p<0.01). CONCLUSIONS: TCRT can
      produce significant response and improvement of survival time in patients with
      advanced gallbladder carcinoma, and may be a favorable alternative to aggressive
      surgical approaches.

PMID- 16001618
TI  - Laparoscopic cholecystectomy: analytical study of 1208 cases.
AB  - BACKGROUND/AIMS: To review our experience and to compare it with similar series
      published in the literature with emphasis on the safety, the rate of conversion,
      the mortality and the morbidity of the procedure. METHODOLOGY: From January 1994
      to February 2003, the files of 1208 cases of laparoscopic cholecystectomy were
      retrospectively analyzed; the technique of surgery as well as the associated co
      morbid conditions, the rate of conversion to open cholecystectomy, and the
      morbidity and mortality was analyzed and compared to other series. Simple
      descriptive statistics were used. RESULTS: The average age was 47.2 +/- 15.1
      years (4-94), there were 878 (72.7%) females and 330 (27.3%) males. Of this
      series 20 patients underwent laparoscopic cholecystectomy while pregnant, 576
      (48%) of the patients had co-morbid conditions. Conversion to open
      cholecystectomy was required in 32 (2.6%) cases and 25 (2.1%) patients had
      complications but no single biliary tract injury was noted. One patient died and
      his death was not directly related to the procedure. The average hospital stay
      was 2.8 (0.5-35) days. CONCLUSIONS: With patience and meticulous technique
      laparoscopic cholecystectomy in the third millennium is safer and quicker than
      open cholecystectomy. Our results compare favorably with those published to date.

PMID- 16001619
TI  - Histopathologic changes in serum bile acid fractions in pressure ulcer patients.
AB  - BACKGROUND/AIMS: Bile acids are synthesized in the liver and released into the
      intestinal tract to aid in digestion and absorption by increasing permeability
      via alteration of the cell membrane. Bedridden elderly patients typically have
      pressure ulcers that may be due to both physical local pressure as well as skin
      cell changes induced by the physiologic effects of bile acids. METHODOLOGY: This
      study investigated 31 elderly bedridden patients with pressure ulcers (mean age,
      81.7 years) and 19 healthy elderly (mean age, 79.7 years). Five serum bile acid
      fractions were summed to determine total bile acid, and transaminase and
      cholesterol levels were also measured. RESULTS: Total cholesterol levels were
      significantly lower (p<0.05) in pressure ulcer patients and transaminase levels
      were not significantly different between the two groups. The primary bile acids
      were generally higher and the secondary and tertiary bile acids lower in pressure
      ulcer patients. In particular, the secondary bile acid deoxycholic acid was
      significantly higher in all pressure ulcer patients. When analyzed by grade of
      pressure ulcer, the primary bile acids were significantly lower in pressure ulcer
      patients. CONCLUSIONS: Secondary bile acid fraction deoxycholic acid measurements
      may indicate bedridden patients at higher risk for pressure ulcers.

PMID- 16001620
TI  - Biliary tract reconstruction with autologous rectus sheath graft--an experimental
      study.
AB  - BACKGROUND/AIMS: Common bile duct injuries which cause significant morbidity and
      mortality are one of the most serious complications of cholecystectomies. They
      can be repaired by various approaches. METHODOLOGY: We used an autologous graft
      obtained from the posterior sheath of the rectus muscle in biliary tract
      reconstruction for common bile duct defect. This experimental study was carried
      out on six dogs. A tissue fragment was excised from the posterior sheath of the
      rectus muscle together with the fascia transversalis and peritoneum. A channel
      from the fascial graft was formed around a T-tube. The autologous rectus sheath
      graft was sutured to the common bile duct as a segmental conduit graft.
      Afterwards, blood biochemistry values and liver histopathology were investigated.
      Dogs were studied by T-tube cholangiography 4 months postoperatively just prior
      to removing the T-tube and again 2 months later at relaparotomy. The hepatic
      parenchyma, intra- and extrahepatic bile ducts were detected by ultrasonography
      during the last 2 months, one time in fifteen days. RESULTS: There was no
      anastomotic insufficiency. The fascial graft gained an appearance similar to bile
      duct in dogs. Postoperatively, no change in blood biochemical parameters was
      observed, and in the preoperative and postoperative periods no histopathological
      change in the liver was found. CONCLUSIONS: These findings indicate that the use
      of an autologous fascial graft to repair common bile duct injuries as a conduit
      graft for segmental bile duct loss may be a feasible and alternative method of
      treatment.

PMID- 16001621
TI  - Hepatobiliary imaging after pancreaticoduodenectomy--a comparative study on
      Billroth I and Billroth II reconstruction.
AB  - BACKGROUND/AIMS: This study was conducted to compare the passage of bile through
      the remnant alimentary tract following pancreaticoduodenectomy in patients
      undergoing Billroth I (Imanaga) and Billroth II (Child) reconstructions, using
      biliary scintigraphy. METHODOLOGY: Seven normal human volunteers and 18 patients
      underwent Child's operation (n=10), or Imanaga's operation (n=8) using
      hepatobiliary scintigraphy. RESULTS: In patients who underwent Child's operation
      (n=10), hepatobiliary scintigraphy showed a prominent stasis of bile tracer in
      the proximal jejunal loop and a significant time delay occurred at the upper
      jejunum. The time taken before visualization of 99mTc at the upper jejunum in the
      patient who underwent Child (65 +/- 5 min) was significantly longer than that in
      the healthy controls. On the other hand, in the patients who underwent Imanaga's
      operation (n=8) no bile stasis in the proximal jejunal loop was found and the
      time taken before visualization of 99mTc of the upper jejunum was similar to that
      of healthy controls (n=7). Continuous stasis of bile in the proximal loop in
      patients who undergo Child's operation can therefore cause reflux cholangitis and
      absorptive disturbances postoperatively in the long term. CONCLUSIONS: The
      results of this study suggest that Imanaga's reconstruction is a more
      physiological procedure than Child's reconstruction following
      pancreaticoduodenectomy.

PMID- 16001622
TI  - The role of extracorporeal shock wave lithotripsy combined with endoscopic
      management of impacted cystic duct stones in patients with high surgical risk.
AB  - BACKGROUND/AIMS: Cholecystoscopic lithotripsy can be an alternative procedure for
      the treatment of impacted cystic duct stones in patients who are high risk for
      surgery. Conventional methods, including electrohydraulic lithotripsy (EHL),
      occasionally fail due to the inability to access or capture the impacted stones
      in the narrow, spirally long cystic duct. Using extracorporeal shock wave
      lithotripsy (ESWL) may be more effective to disintegrate cystic duct stones. The
      aim of the study is to evaluate the role of ESWL in the endoscopic treatment of
      impacted cystic duct stones in patients with high operative risk. METHODOLOGY:
      Eleven patients with impacted cystic duct stones who were at high risk for
      surgery were included in this study. All of them had had a failed initial attempt
      of percutaneous transhepatic cholecystoscopic lithotripsy (PTCCS-L) followed by
      percutaneous transhepatic cholecystostomy. Patients underwent ESWL to
      disintegrate cystic duct stones with endoscopic removal of fragmented stones.
      RESULTS: Complete removal of cystic duct stones was achieved in 9 of 11 patients
      (81.8%). One of the 9 patients (11.1%) was treated solely with ESWL, but the
      other 8 patients (88.9%) required cholecystoscopic removal of residual fragmented
      stones after ESWL. Fragmented stones passing through the cystic duct impacted in
      ampullary region in 3 patients after ESWL. Two patients required transpapillary
      removal of stones. CONCLUSIONS: Endoscopic stone removal after ESWL for impacted
      cystic duct stones is a difficult and time-consuming procedure. But, it seems to
      be a relatively safe alternative to surgery in patients with high surgical risk.

PMID- 16001623
TI  - Surgical management of choledochal cysts in adults.
AB  - BACKGROUND/AIMS: Choledochal cysts are congenital malformations of the
      pancreatico-biliary system. Some aspects of optimal surgical management of
      choledochal cysts remain controversial. The purpose of this paper is to present
      our series of 14 patients with choledochal cysts, analyzing surgical management
      and long-term results. METHODOLOGY: Between January 1975 and December 2001, 15
      adult patients with choledochal cysts were treated at our Department. Sex, age,
      clinical symptoms, associated diseases, surgical management and postoperative
      morbidity and mortality were reviewed. Choledochal cysts were classified
      according to the Alonso-Lej classification with Todani et al.'s, modification,
      based on radiographic and operative findings. RESULTS: There were 15 patients, 6
      males and 9 females, with an age ranging from 28 to 82 years and a mean age at
      the time of surgery 58.3 years. Seven patients had a solitary fusiform
      extrahepatic cyst (Type I), five patients had an extrahepatic supraduodenal
      diverticulum (Type II), one patient had a choledochocele (Type III), while two
      patients had a Type IVB cyst. Symptoms were vague and intermittent. Recurrent
      upper abdominal pain, jaundice, fever, nausea and vomiting were the most common
      findings, usually occurring in combination. Two patients presented with
      cholestatic cirrhosis. Five patients had laboratory evidence of hepatocellular
      dysfunction and two patients had hyperamylasemia. A variety of operations was
      performed such as cystoduodenostomy, cyst excision and hepaticojejunostomy, cyst
      excision and choledochoduodenostomy. Postoperative follow-up ranged from 30
      months to 12 years in all patients except of two patients who were lost to follow
      up. CONCLUSIONS: Total or partial excision of the choledochal cysts is the
      optimal treatment because of the lower incidence of postoperative complications
      and the better survival rate after the operation.

PMID- 16001624
TI  - Papillary carcinoma of the gallbladder and anomalous pancreatico-biliary
      junction. Report of three cases and review of the literature.
AB  - BACKGROUND/AIMS: Papillary carcinoma of the gallbladder is less invasive, less
      frequently metastasizes and results in a longer survival than other gallbladder
      tumors. It is frequently associated with Anomalous Pancreatico-biliary junction
      (APBJ), a malformation that occurs most frequently in Japan. Consequently, most
      cases of papillary cancer have been reported in the Japanese literature, while
      the incidence of this neoplasm, and its association with APBJ, is still unknown
      in Western Countries. METHODOLOGY: Seventy cases of gallbladder cancer, observed
      between January 1992 and December 2000, were retrospectively evaluated. All the
      histological sections and available cholangiograms were reviewed. RESULTS: Three
      cases of papillary carcinoma were found (4.2%); APBJ was detected in one of
      these. All patients underwent resection and are long-term survivors; one patient
      developed, three years later, a papillary cancer of the common bile duct and was
      treated by Whipple's procedure. CONCLUSIONS: This study provides evidence that
      papillary carcinoma is more rare in Western countries than in Japan and it is
      characterized by a longterm survival after surgical resection. Further studies
      and reports are necessaries to define if this different incidence can justify
      differences between Western and Japanese results after surgery for gallbladder
      cancer.

PMID- 16001625
TI  - Overlapped-clipping, a new technique for ligation of a wide cystic duct in
      laparoscopic cholecystectomy.
AB  - A wide or enlarged cystic duct is a common encounter in laparoscopic
      cholecystectomy. Many techniques are used to secure its ligation; including
      internal or extracorporeal knots and Roeder knot. A preformed knot can be used
      e.g. ETHIBINDER; the Endoloop. The Endo GIA is a useful stapling device but is
      more expensive. Other simpler techniques have also been described. The author
      developed a new, simple, safe and quick technique to ligate the wide cystic duct
      utilizing the commonly used multiple clip appliers. The technique does not need
      special skill or instruments and ensures complete ligation of the wide cystic
      duct using overlapping of the clips.

PMID- 16001626
TI  - Bile duct carcinoid tumors: an uncommon disease but with a good prognosis?
AB  - Carcinoid tumors of the biliary tract are exceedingly uncommon. We report 3 cases
      of primary carcinoid tumors of the biliary tract, which are compared to the
      reported patients in the literature and to the patients' data with other types of
      biliary malignancies in our experience. SETTING: Retrospective analysis in a
      single academic institution. From a consecutive series of 79 resected tumors of
      the biliary tract between 1979 and 2002, 3 patients were found to suffer from
      primary carcinoid tumors (3.8%). There were 2 males and one female patient, with
      a mean age of 56 years old (range: 46-73), younger than other malignant biliary
      cancer cases. Clinical presentation included obstructive jaundice in 2 patients.
      There were no signs of diarrhea or carcinoid syndrome. Location of the tumor
      included the extrahepatic bile duct in all patients. Two of these patients had a
      polypoid tumor obstructing the bile duct. The disease was localized in 2
      patients, but with liver metastases in the remaining patient. Final diagnosis was
      achieved on final pathological examination in 2 patients, but preoperative
      endoscopic biopsies allowed correct diagnosis of nature and tumor staging by
      octreotide scintigraphy in one patient. Radical resection was achieved in 2
      patients with long-term cure at 8.5 and 9.5 years, respectively. A high-risk
      patient with a small residual liver metastasis after resection is still alive and
      disease-free under LAR Octreotide SC administration at 17 months postoperatively.
      The median survival time for patients suffering from carcinoid tumors was 102
      months while it was 33 months for patients suffering from cholangiocarcinomas in
      our experience. Carcinoid tumors of the biliary tract are exceedingly rare.
      Preoperative diagnosis is uncommon but possible by endoscopic biopsies. Radical
      resection seems to be associated with a longer survival than classical
      cholangiocarcinoma.

PMID- 16001627
TI  - Percutaneous drainage under real-time computed tomography-fluoroscopy guidance.
AB  - BACKGROUND/AIMS: The goal of our study was to assess the use of real-time
      computed tomography-fluoroscopy guidance for percutaneous drainage of abnormal
      thoracic, abdominal, and pelvic fluid collections. METHODOLOGY: The subjects were
      32 patients who underwent 36 percutaneous computed tomography-fluoroscopy guided
      thoracic, abdominal, and pelvic drainage procedures to drain abscess (n=29),
      fluid collection after pancreatitis (n=3), lymphocyst after gynecological surgery
      (n=3), and the gallbladder transhepatically (n=1) between September 1997 and
      August 2003. The patient population was 28-86 years old and consisted of 19 men
      and 13 women. The drainage methods included a Seldinger's technique with a
      guidewire and serial dilators in every case. The procedures were guided by using
      a helical computed tomography scanner that provided real-time fluoroscopy
      reconstruction. RESULTS: Percutaneous drainage under real-time computed
      tomography-fluoroscopy guidance was successfully performed in every procedure.
      Real-time computed tomography-fluoroscopy allowed rapid assessment of needle,
      guidewire, dilator, and catheter placement. The only drainage-induced
      complication encountered was a subcutaneous hematoma after one procedure (2.8%).
      No patients had serious complications. The average procedure time was 32 minutes.
      CONCLUSIONS: Computed tomography-fluoroscopy is a useful method for guiding the
      accurate and safe drainage of abnormal thoracic, abdominal, and pelvic fluid
      collections.

PMID- 16001628
TI  - Sealing the thoracic duct with ultrasonic coagulating shears.
AB  - BACKGROUND/AIMS: Ultrasonic coagulating shears were developed as an endosurgical
      device that allows cutting of vessels without ligation. In this study, we
      obtained basic data on the feasibility of dividing and sealing the thoracic duct
      by using ultrasonic coagulating shears. METHODOLOGY: We obtained the thoracic
      duct and the left gastric artery from surgical specimens of 27 patients. After
      one end of each vessel was sealed using ultrasonic coagulating shears, we
      recorded the bursting pressure. The sealed ends of the vessels were also examined
      histopathologically. RESULTS: The mean bursting pressure of the thoracic duct was
      high enough to support the clinical use of this device, and was significantly
      higher than that of the left gastric artery (p<0.001). Microscopic examination of
      the sealed vessels showed that degenerated collagen fibers were more homogeneous
      and covered a significantly larger area in the thoracic duct than in the left
      gastric artery (p<0.001). CONCLUSIONS: The present study provides a basis for
      using ultrasonic coagulating shears to seal the thoracic duct and possibly lymph
      node dissection.

PMID- 16001629
TI  - Enzyme histochemical analysis of lymphatic vessels in colon carcinoma: occurrence
      of lymphangiogenesis within the tumor.
AB  - BACKGROUND/AIMS: While it is generally recognized that the lymph vessel is absent
      in solid carcinoma, a few papers have reported the presence of intratumoral lymph
      vessels. The present study was carried out to clarify whether or not intratumoral
      lymphangiogenesis occurs. METHODOLOGY: To identify lymphatics in colon
      carcinomas, tumor-adjoining and normal submucosa, we tried using an enzymatic
      histochemistry procedure to examine the specific high activity of 5'-nucleotidase
      that is seen in lymphatic endothelial cells. Additionally, arterioles and venules
      were identified by alkaline phosphatase and dipeptidyl (amino) peptidase IV
      staining, respectively. RESULTS: Intratumoral lymphatic vessels were observed in
      30 of 34 colon carcinomas (91%), and arterioles were found in all cases. However,
      no venules were identified within the tumor. The lymphatic density (mean +/- SD
      vessels/mm2) increased in the order of the submucosa near the tumor (21.9 +/-
      9.5), normal submucosa (27.9 +/- 13.8) and tumor tissue (33.9 +/- 25.1).
      Intratumoral lymphatic density was significantly higher than that in the
      submucosa near the tumor (P<0.05). Intratumoral lymphatic density is related to
      arteriolar density (r=0.284, P=0.0012). The ratio of lymphatic/arteriolar density
      in the tumor was significantly higher than that seen in the submucosa near the
      tumor (0.78 +/- 0.76 vs. 0.51 +/- 0.36, P<0.05). Intratumoral lymphatic density
      was relatively higher in cases with lymph node metastasis than in those without
      metastasis, but was not related to tumor size, depth of tumor invasion, distant
      metastasis and TNM stage. CONCLUSIONS: Enzyme histochemistry revealed active
      lymphangiogenesis and the absence of venules within the tumor. Intratumoral
      lymphatic density was relatively correlated to arteriolar density. Enzyme
      histochemistry is a simple and quickly processed method that can be used to
      differentiate lymphatics from arterioles and venules.

PMID- 16001630
TI  - Regional portal hypertension diagnosed by ultrasonography: imaging findings and
      diagnostic values.
AB  - BACKGROUND/AIMS: To investigate the diagnostic accuracy of ultrasonography for
      regional portal hypertension (RPH) and ascertain the best diagnosis method for
      RPH. METHODOLOGY: Eleven cases of regional portal hypertension diagnosed by
      ultrasonography were retrospectively studied. Their etiological features,
      clinical findings, and ultrasonographic diagnosis criteria were analyzed. Other
      diagnostic approaches were also compared and related literature was reviewed.
      RESULTS: Eleven patients were all verified by operation. The diagnostic accuracy
      of color Doppler ultrasonography was 100%. The etiological diagnostic accuracy
      was 91% (10/11). CONCLUSIONS: Color Doppler ultrasonography should be considered
      as the first choice to diagnose RPH due to its safety, accuracy, and simplicity.
      RPH can be classified etiologically into 3 types: pancreatic RPH, splenic RPH,
      retroperitoneal RPH.

PMID- 16001631
TI  - Mucin and differentiation in Epstein-Barr virus-associated gastric carcinoma.
AB  - BACKGROUND/AIMS: Epstein-Barr virus (EBV) is present in roughly 1 in 10 cases of
      gastric carcinoma, particularly in undifferentiated adenocarcinomas. To clarify
      the histological developmental processes in EBV-associated gastric carcinoma, we
      investigated the presence of EBV infection, changes in the degree of
      differentiation within lesions, and mucin phenotypes of gastric carcinomas.
      METHODOLOGY: We had already examined 124 gastric carcinomas using in situ
      hybridization for EBV-encoded small RNA1 (EBER-1) and 12 lesions were EBER-1
      positive. From these lesions we selected 8 carcinomas positive for EBER-1, and
      then chose 16 EBER-1-negative carcinomas as controls. Hematoxylin and eosin (H&E)
      stained specimens were examined for changes in histological type within each
      lesion. Mucin phenotypes of the specimens were determined using human gastric
      mucin (HGM), MUC2 and CD10 immunostaining. RESULTS: Of the EBER-1-positive
      lesions, 50% exhibited the gastric type mucin phenotype, whereas only 19% of the
      EBER-1-negative lesions were of the gastric phenotype. Changes in the
      histological type were seen within 75% of the EBER-1-positive lesions and within
      62.5% of the EBER-1-negative lesions. CONCLUSIONS: The gastric mucin phenotype
      tended to be more common in the EBV-associated gastric carcinomas. The influence
      of EBV infection on the change in the histological type within the lesion was
      considered to be slight.

PMID- 16001632
TI  - The significance of CD44 expression in gastrointestinal neuroendocrine tumors.
AB  - BACKGROUND/AIMS: Expression of CD44 and its isoforms has been demonstrated to be
      a prognostic marker in many neoplasms. Gastrointestinal neuroendocrine tumor is a
      slow-growing neoplasm, whose behavior is determined by site of occurrence, size
      or specific histologic growth pattern. In this study, the feasibility of using
      CD44 as a prognostic marker in gastrointestinal neuroendocrine tumor is
      evaluated. METHODOLOGY: Representative paraffin-embedded sections of
      gastrointestinal neuroendocrine tumor from 22 patients were studied by
      immunohistochemical staining using monoclonal antibodies against CD44, Ki-67, and
      p53 retrospectively. The correlation between these markers and clinical behavior
      of the tumors was analyzed. RESULTS: Positive expression of CD44 was observed in
      15 cases (68%) of gastrointestinal neuroendocrine tumor. Expression of CD44
      showed significant inverse correlation with lymph node status (P=0.049), distant
      metastasis (p<0.001) and mortality (p=0.002). Neither p53 nor Ki-67 correlated
      with lymph node status, distant metastasis and overall survival. Both lymph node
      status and distant metastasis showed strong correlation to survival after
      multivariate analysis. Patients with the tumor growing from the hindgut had
      better survival (p=0.024). The patients with stronger CD44 immunoreactivity (> or
      = 2+) tumors had significantly favorable survival (p=0.004) compared with those
      with weaker immunoreactivity (< or = 1+) tumors. CONCLUSIONS: Expression of CD44
      in gastrointestinal neuroendocrine tumor inversely correlates with tumor
      metastasis, associates with a favorable outcome and may serve as one of the
      prognostic indicators.

PMID- 16001633
TI  - Reappraisal of a method of reconstruction after pancreatoduodenectomy.
AB  - BACKGROUND/AIMS: After pancreatoduodenectomy (PD), pancreatic leak and the
      functional pancreatic and gastrointestinal disorders are the most important
      complications. Still there is no single method which takes care of all of them.
      After identifying the various reasons behind these complications, the senior
      author started performing the present method in the 1980s. Since then we have
      been able to bring these complications to a very low incidence. The present study
      is designed to substantiate the claims of various advantages of this method of PD
      and reconstruction and to explain the rationale behind this method. METHODOLOGY:
      This is a retrospective study of 225 consecutive PD procedures done for
      periampullary cancers, during the period of 1993-2004. The shortterm and long
      term results assessed were mortality rate, morbidity rate, early reoperation,
      survival, steatorrhea, pancreatic enzyme supplementation requirement, occurrence
      of bile gastritis, dumping, new onset of diabetes, marginal ulcers, cholangitis,
      postoperative weight trends and frequency of hospital readmission for symptom
      management. Follow-up was done 6 monthly in all the patients with the aim of
      diagnosis of recurrence and assessment of long-term gastrointestinal and
      pancreatic function and nutritional status. In addition, in 15 patients, upper
      gastrointestinal endoscopy (UGIE) with gastric and jejunal biopsy, 99Tc-HIDA
      scan, determination of fecal fat loss after a standard 100-g fat diet for three
      days, fecal elastase-1 measurement (ELISA) and MRCP were done to objectively
      document the changes in gastrointestinal and pancreatic function. The data were
      compared with the results available in the literature. RESULTS: The mean age was
      56 years with a range of 27-85 years. There were 130 males and 95 females.
      Preoperatively 18 patients had diabetes and preoperative weight loss varied from
      5-30 kilograms with a mean of 12 kilograms. Of all the PD cases 57 were for
      ampullary, 70 were for lower end cholangiocarcinoma and 98 were for pancreatic
      head cancer. The postoperative complications occurred in the form of intra
      abdominal bleed (5), pancreaticojejunostomy leak (12), intra-abdominal abscess
      (4) and pneumonia (5). Delayed gastric emptying was not seen in any of the
      patients. In 8/12 patients with PJ leak the closure was achieved with the
      conservative treatment. The 30-day mortality was 6/225 (2.66%). The causes were
      sepsis in 3, intra-abdominal bleed in 2 and pulmonary embolism in 1 patient.
      There was no mortality related to PJ leak. The median follow-up was of 36 months.
      The overall 5-year survival for ampullary, lower end cholangio- and pancreatic
      head carcinoma were 65%, 25% and 20% respectively. After surgery none of the
      patients had clinical evidence of steatorrhea, gastritis, peptic ulcer disease,
      cholangitis, dumping and there was no new case of diabetes. After 6-12 months 80%
      of the patients gained weight similar to their preoperative levels. UGIE with
      gastric and jejunal biopsies, 99Tc-HIDA scan, fecal fat loss estimation, fecal
      elastase estimation and MRCP were done in 15 patients and were found to be
      normal. CONCLUSIONS: Our method of PD and reconstruction produces encouraging
      results with respect to PJ leak, mortality, DGE, malabsorption, bile gastritis,
      dumping, marginal ulcers and diabetes. We recommend this technique as a safe and
      effective method even to the low volume centers.

PMID- 16001634
TI  - Successful surgical treatment for hepatocellular carcinoma and concomitant risky
      esophageal varices.
AB  - BACKGROUND/AIMS: In our frequent encounters with liver cirrhotic patients with
      hepatocellular carcinoma (HCC) and concomitant risky esophageal varices, we have
      found that some of them required endoscopic injection sclerotherapy (EIS) and/or
      surgical treatment for esophageal variceal bleeding due to increased portal
      venous pressure after aggressive hepatectomy. In this study, we investigated the
      short-term effect of aggressive hepatectomy accompanied with left gastric venous
      caval shunt (Inokuchi's shunt) for esophageal varices and postoperative liver
      function. METHODOLOGY: Four cirrhotic patients with HCC and concomitant risky
      esophageal varices underwent hepatectomy with Inokuchi's shunt from 1999 to 2001.
      The mean age was 58.0 +/- 15.3 years old and all patients were classified in
      Child grade A or B. We investigated hematochemical data and endoscopic findings
      before and after surgery. RESULTS: One of the patients experienced disappearance
      of esophageal varices at discharge. In the others, postoperative endoscopy showed
      disappearance of CRS and reduced sizes of varices. In one patient, hepatic
      encephalopathy appeared transiently with bleeding from a duodenal ulcer at one
      month after surgery. However, the patient improved by conservative treatment.
      Three of the patients have survived well without recurrence of HCC and esophageal
      variceal bleeding; the remaining patient died from a recurrence of HCC.
      CONCLUSIONS: Inokuchi's shunt may be sufficiently effective to treat risky
      esophageal varices associated with resectable HCC and may be safe even if it is
      undertaken along with a major hepatectomy.

PMID- 16001635
TI  - Localized visceral invasion of peritoneal mesothelioma causing intestinal
      obstruction: a new clinical presentation.
AB  - Peritoneal mesothelioma is a surface malignancy involving the serous surfaces of
      the abdominal cavity. In the case presented here, the disease presented itself in
      a manner that has not been previously described. The tumor involved the full
      thickness of the bowel besides the familiar surface spread which is
      characteristic of the disease. Intestinal obstruction is a rare or late
      presentation of mesothelioma. It was the presenting symptom in the present case
      due to the full thickness infiltration of the small bowel by the tumor. The
      offending segment was resected and the ascites was treated with intraperitoneal
      chemotherapy. Though the patient at present has progression of disease he enjoys
      a reasonable quality of life after palliation of the ascites and obstruction.

PMID- 16001636
TI  - Modified extended distal pancreatectomy for carcinoma of body and tail of
      pancreas.
AB  - The prognosis of carcinoma in the body and tail of the pancreas is disappointing
      due to the low rate of resectability, since it is usually presented at an
      advanced stage with local invasion of adjacent major vessels. However, the
      postoperative survival, if resectable, is similar to carcinoma of the pancreatic
      head. Aggressive approach, by applying extended distal pancreatectomy with the
      resection of the celiac axis, may increase the resectability but promote the
      potential risk of hepatic dysfunction and biliary necrosis after the sudden
      interruption of the common hepatic artery. We modified the procedure by
      reanastomosis between the stump of the celiac axis and common hepatic artery
      without vascular graft to manage a 50-year-old woman with locally advanced
      carcinoma of the body and tail of pancreas. She had 2 years of disease-free
      survival. This modified extended pancreatectomy may be a feasible and safer
      procedure.

PMID- 16001637
TI  - Biliobiliary fistulas manifested by worsening liver function--a case report.
AB  - We report a case of cholecystolithiasis with biliobiliary fistulas from
      gallbladder to hepatic ducts, which were manifested by worsening liver
      dysfunction. Although it was not diagnosed preoperatively, it was successfully
      treated by cholecystectomy with closure of fistulas by the gallbladder wall. This
      case suggests that an internal biliary fistula may be possible, when the
      gallbladder wall is thickened and shrunken in the case of cholecystolithiasis,
      accompanied with liver dysfunction despite no dilatation of the common bile duct.

PMID- 16001638
TI  - Preoperative chemoradiotherapy in patients with locally advanced rectal cancer.
AB  - BACKGROUND/AIMS: To determine the percentage of responders and the resectability
      rate for patients with locally advanced carcinoma of the rectum treated by
      infusional 5-fluorouracil chemotherapy and pelvic radiation. METHODOLOGY: Twenty
      four patients with a diagnosis of locally advanced unresectable rectal cancer
      received preoperative 5-fluorouracil by intravenous infusion at the dose of 250
      300mg/m2/day concurrent with pelvic radiation (median 50.4 Gy/28 fractions).
      Surgery was performed with a mean delay of 15 days after completion of
      irradiation and included 11 abdominoperineal resections and five anal sphincter
      preserving procedures. RESULTS: The median follow-up was 22 months. Complete
      histological response occurred in 6%, and tumor down-staging in 58% of cases.
      There was a significant difference in the rate of local control based on the
      distance of the tumor from the anal verge (>5.4cm; p=0.046). Our results have
      suggested the importance of the total dose on the local control (p=0.061). Higher
      local failure rate has been observed with prolonged treatment time (p=0.018).
      With metastasis-free survival as the endpoint, only stage (p=0.027) was a
      statistically significant prognostic factor. CONCLUSIONS: The favorable influence
      of higher doses of preoperative radiotherapy on pathologic stage has been
      observed. Even after preoperative radiotherapy, postoperative staging remained a
      prognostic factor.

PMID- 16001639
TI  - Ileal-pouch-anal anastomosis after restorative proctocolectomy in patients with
      ulcerative colitis or familial adenomatous polyposis.
AB  - BACKGROUND/AIMS: Restorative proctocolectomy is the "golden standard" in surgical
      treatment of ulcerative colitis and familial adenomatous polyposis. The two
      alternative techniques of ileal-pouch-anal anastomosis include hand-made suture
      and double line stapled suture. The aim of the study was the analysis of
      postoperative complications and functional results of the two types of
      anastomosis. METHODOLOGY: Analyzed group consisted of 71 patients operated
      between 1994 and 2003 for ulcerative colitis (n=62) or familial adenomatous
      polyposis (n=9). Stapled anastomosis was performed in 56 (79%) cases whereas hand
      made suture was performed in 15 (21%) cases. RESULTS: No significant differences
      between the two anastomosis techniques were found in terms of postoperative
      complications as well as late functional results. CONCLUSIONS: The low rate of
      complications and well accepted functional outcome prove that restorative
      proctocolectomy is a safe surgical procedure which may be offered to patients
      with ulcerative colitis of familial adenomatous polyposis. Double line stapled
      suture should be the preferred method of ileal-pouch-anal anastomosis, however
      hand-made suture remains its valuable alternative and may be considered in
      selected cases.

PMID- 16001640
TI  - Decreased cell-mediated immune status in colorectal cancer patients with hepatic
      metastasis.
AB  - BACKGROUND/AIMS: Depression of cell-mediated immunity frequently accompanies
      solid tumor malignancy, and appears to be worsened as the disease progresses. In
      this study, we investigated cell-mediated immune status in colorectal cancer
      patients. METHODOLOGY: Interleukin-2 (IL-2) productivity by phytohemagglutinin
      (PHA)-stimulated non-adherent peripheral blood mononuclear cells (PBMC), and
      prostaglandin E2 (PGE2) productivity by LPS-stimulated adherent PBMC were
      investigated in colorectal cancer patients with hepatic metastasis (n=20) and
      without hepatic metastasis (n=20), and in non-malignant disease controls (n=20).
      Percentages of peripheral blood T-cell subsets and NK activity were also
      investigated. RESULTS: In the colorectal cancer patients with hepatic metastasis
      IL-2 productivity was significantly decreased, compared with the controls.
      However, the percentages of T-cell subsets and NK activity were not significantly
      different among the groups. Meanwhile, PGE2 productivity in the patients with
      hepatic metastasis was significantly increased, compared with the other groups,
      and was significantly correlated with the hepatic tumor load. CONCLUSIONS: Tumor
      bearing state, especially metastasis to the liver, may influence immune status of
      the patient. For evaluating cellular immunity status, cytokine productivity by
      activated lymphocytes and monocytes may be a more sensitive marker rather than
      other conventional immunological parameters, and may also provide useful
      information for immune intervention in the treatment of patients from this point
      of view.

PMID- 16001641
TI  - Surgical therapy of adenocarcinoma of the esophagogastric junction: analysis of
      prognostic factors.
AB  - BACKGROUND/AIMS: The surgical strategy of adenocarcinoma of the esophagogastric
      junction (EGJ) is still controversial. This study aims at analyzing our surgical
      results about these lesions in order to define the prognostic factors.
      METHODOLOGY: From January 1987 to March 2003, 113 patients with adenocarcinoma of
      the cardia underwent resection in the authors' institution: 19 patients (16.8%)
      had type I tumors, 35 (30.9%) type II and 59 (52.2%) type III. The treatment was
      esophagectomy for type I tumors, and extended gastrectomy and distal
      esophagectomy for type II and III lesions. Morbidity, mortality and the survival
      rate were determined retrospectively. RESULTS: Primary resection was performed in
      113 patients out of 150 (75.3%). Mortality and morbidity rates were 7.96 and
      38.05% respectively. The overall 3- and 5-year survival rates were 35.1 and 26.3%
      respectively. Survival rates were significantly associated with R0 resection
      (P<0.001), pathological node-positive category (P<0.001) and tumor
      differentiation (P=0.0228). CONCLUSIONS: The prognosis of adenocarcinoma of the
      EGJ is still unfavorable, but the true prognostic factors are complete
      macroscopic and microscopic tumor resection, pN category and tumor
      differentiation. Although the surgical approach does not influence the survival
      rate, the transhiatal way still remains the best one due to the lower incidence
      of respiratory morbidity and thoracic pain.

PMID- 16001642
TI  - Breast carcinoma metastasis to the esophagus: report of two cases.
AB  - A retrospective case report which describes two unusual cases of esophageal
      metastasis from breast cancer. Esophageal metastasis was detected in two women 10
      and 23 years after mastectomy for breast cancer. Both lesions presented as a
      smooth constriction of the esophagus covered by normal esophageal mucosa that
      confounded gross and histologic diagnosis via endoscopy and biopsy. Ultrasound
      guided, fine-needle aspiration led to the correct diagnosis preoperatively in one
      case. One patient successfully underwent surgical resection and was without
      recurrence one year later. The other patient had other multiple lesions and is
      receiving hormone therapy after insertion of an expandable metallic stent in the
      esophagus. Esophageal metastasis from breast carcinoma is rare, but does occur.
      Often presenting long after initial therapy, an aggressive approach may be
      justified if this is a solitary lesion.

PMID- 16001643
TI  - Can 13C urea breath test predict resistance to therapy in Helicobacter pylori
      infection?
AB  - BACKGROUND/AIMS: Results of 13C urea breath test (UBT), a noninvasive test for
      detecting active H. pylori infection, have been regarded also numerically for a
      possible predictive value on bacterial load and entity of mucosal inflammation.
      In the present study we wished to determine whether there is a particular value
      of Delta Over Baseline (DOB) result which could predict resistance to anti-H.
      pylori therapy. METHODOLOGY: 570 subjects from 1376 tested received a standard
      triple anti-H. pylori regimen. After a minimum of 6 weeks subjects underwent
      control UBT testing. Correlation of DOB values at diagnostic and control UBT and
      sensitivity of different DOB levels to predict resistance to therapy were
      calculated using simple linear correlation and Bayes' theorem, respectively.
      RESULTS: Modest linear correlation was observed between DOB values (r2=0.28). The
      value of 13.0 at diagnostic UBT showed a sensitivity of 65.5% to predict and
      further positivity at control testing. CONCLUSIONS: In our large series, UBT
      numerical DOB value weakly predicted resistance to first-line anti-H. pylori
      therapy.

PMID- 16001644
TI  - Outcomes of emergency surgical treatment in malignant bowel obstructions.
AB  - BACKGROUND/AIMS: Malignant bowel obstructions are still a challenging problem for
      surgeons and carry high morbidity and mortality risk. The aim of this study was
      to review the presentation and outcomes of malignant bowel obstructions and to
      identify the risk factors related with poor prognosis. METHODOLOGY: One hundred
      and twenty-five patients underwent emergency surgical treatment for malignant
      obstructions between January 1997 and January 2002. Data included age, sex, past
      medical history, presenting symptoms; physical findings on admission, American
      Society of Anesthesiologists (ASA) class, operative details, postoperative
      complications, length of hospitalization and hospital mortality were reviewed
      retrospectively. RESULTS: Seventy-three (58%) of the patients have poor
      performance status on admission. Potentially curative resection was performed in
      74 (60%) patients. Surgical treatment was palliative in 43 (34%) patients.
      Extended bowel resections were utilized in 20 (16%) patients. Our hospital
      mortality rate was 21%, and postoperative morbidity rate was 31%. Coexisting
      cardiopulmonary diseases, presence of generalized perforation, poor general
      condition and extended bowel resections appeared to be related with unfavorable
      outcomes. CONCLUSIONS: Emergency surgical treatment for malignant obstruction may
      be curative in selected patients with good performance status.

PMID- 16001645
TI  - CD19+ in intestinal mucosa predict the response to infliximab in Crohn's disease.
AB  - BACKGROUND/AIMS: Infliximab is an effective treatment for Crohn's disease, yet
      about 30% of patients have a weak or no response. The aim of the study was to
      determine if the likelihood of a patient achieving complete remission 3 months
      after treatment with infliximab can be predicted from immunological parameters
      measured in peripheral blood and inflamed intestinal mucosa before the treatment.
      METHODOLOGY: 25 patients with Crohn's disease resistant to conventional therapy
      underwent treatment with infliximab. Samples of peripheral blood and inflamed
      intestinal mucosa were analyzed by flow-cytometry before infliximab
      administration. The clinical response was evaluated after 3 months. RESULTS: At 3
      months post-treatment, 11 (44%) patients were in complete remission, while 14
      (56%) had no remission. Logistic regression analysis revealed that 50% of
      patients having 2.29% of CD19+ cells in inflamed intestinal mucosa may be
      expected to achieve complete remission. If the proportion of CD19+ cells in the
      inflamed mucosa is 5%, the probability of the patient achieving complete
      remission following treatment rises to 85%. CONCLUSIONS: This is the first study
      which found that a high percentage of CD19+ cells in the inflamed intestinal
      mucosa of a patient with Crohn's disease may predict long remission after
      infliximnab therapy.

PMID- 16001646
TI  - Upper gastrointestinal disorders induced by non-steroidal anti-inflammatory
      drugs.
AB  - BACKGROUND/AIMS: We examined the characteristics of upper gastrointestinal (GI)
      disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs). METHODOLOGY:
      The questionnaire investigation was performed over a five-year period. RESULTS: A
      study was performed on 354 patients (161 men and 193 women with mean ages of 66.0
      and 70.7 years, respectively) who developed NSAID associated upper GI disorders:
      21 patients had acute gastric mucosal lesion (AGML), 212 had gastric ulcer, 63
      had duodenal ulcer, 17 had gastroduodenal ulcers and 41 other cases. About 75% of
      patients received NSAIDs for orthopedic conditions. Sixty percent of gastric
      disorders induced by NSAIDs affected the antrum or angulus of the stomach. The
      incidence of disorders of the gastric antrum was significantly higher in women
      than in men whilst the incidence of disorders on the gastric angulus was
      significantly higher in men than in women (p<0.05). The proportion of patients
      with GI symptoms was significantly lower in patients over 65 years old than in
      those under 65 years old (p<0.05). The time taken to achieve the healing stage
      was significantly longer in patients with greater than 3 months NSAID ingestion
      compared to patients that had received NSAIDs for less than 3 months (p<0.05).
      CONCLUSIONS: We should examine the association between upper GI disorders induced
      by NSAIDs and H. pylori as well as the rate of GI disorders induced by new Cox-2
      inhibitors.

PMID- 16001647
TI  - Angiosarcoma in the small intestine. Apropos of a particular case.
AB  - Presentation of a case of small intestine primary angiosarcoma in a 70-year-old
      male. There is question of an extremely rare tumor in the gastrointestinal tract.
      Its symptomatology is similar to that of other tumors in the small intestine. An
      immunohistochemical study is usually essential for its anatomopathological
      diagnosis. The diagnosis is generally arrived at in its advanced stages, and that
      makes for a bad prognosis. The bibliography has been revised from this case on.

PMID- 16001648
TI  - Ampullary carcinoma associated with protein-losing gastropathy due to diffuse
      varioliform gastritis.
AB  - Protein-losing gastropathy due to diffuse varioliform gastritis is a rare
      condition, and its occurrence accompanying ampullary carcinoma is particularly
      rare. We report here a case of ampullary carcinoma accompanied with protein
      losing gastroenteropathy due to diffuse varioliform gastritis. A 39-year-old
      Japanese woman was admitted to our hospital because of general fatigue and
      generalized edema. Her total protein level was 3.1g/dL, with an albumin level of
      1.4g/dL, and hemoglobin level of 6.9g/dL. Upper gastrointestinal endoscopic
      examination showed diffuse varioliform gastritis and carcinoma of the papilla of
      Vater. A diagnosis of protein-losing gastropathy was made based on the results of
      scintigraphy using technetium 99m-labeled human albumin. Continuous bleeding from
      ampullary carcinoma caused anemia and deteriorated hypoproteinemia.
      Pancreaticoduodenectomy was performed for ampullary carcinoma prior to
      Helicobacter pylori eradication. The tumor was a papillary adenocarcinoma, which
      had invaded the lamina muscularis propria over the sphincter of Oddi; the
      resected stomach revealed typical hyperplastic lymphocytic gastritis. H. pylori
      were detected on microscopic analysis. Scintigraphy after surgery showed no
      accumulation of the tracer in the bowel. Anemia, hypoalbuminemia and diffuse
      varioliform gastritis are improved 6 months after surgery and H. pylori
      eradication, and the patient is currently free from disease.

PMID- 16001649
TI  - Repeated instillation of a limited volume of ethanol for the treatment of
      symptomatic hepatic cysts.
AB  - BACKGROUND/AIMS: In the past, various treatments for symptomatic hepatic cysts
      have been reported. In recent years, sclerosis therapy seems to be most common.
      In the present study, repeated instillation of a limited volume of ethanol was
      evaluated. METHODOLOGY: Six patients who had one or more hepatic cysts underwent
      percutaneous alcohol sclerosis therapy. Of the six patients, five had epigastric
      discomfort, and one had back pain. A 7.0-French pigtail polyethylene catheter was
      inserted into the cyst. The fluid was aspirated and it was demonstrated by
      radiograph that there were no communications between the cysts and the
      intrahepatic duct or hepatic vessels. Six hepatic cysts were instilled with 99%
      sterile ethanol, which was allowed to remain in place for 5 minutes, and then
      removed. Ethanol instillation was repeated every day or every other day in all
      patients. It was performed two to five. Ethanol volume of a single instillation
      varied from 10mL to 100mL. In all cases, the ethanol volume of first instil
      lation was limited to 20mL or less to prevent severe complications. RESULTS: The
      diameters of the initial cysts ranged from 7.8 to 13.2cm (mean, 10.4cm) and
      aspirated fluid volume varied from 70 to 1000mL (mean, 455mL). All patients had
      slight alcohol intoxication for a few hours after alcohol instillation, two had
      moderate abdominal pain at the time of alcohol instillation. In five of six
      patients, subtotal or total regression of the hepatic cysts was observed within
      eight months following treatment. In one case, the hepatic cyst was reduced from
      13x11 to 7.8x7.5cm in size after seven months, but further regression was not
      obtained thereafter. All patients became symptom-free. CONCLUSIONS: It is
      concluded that repeated instillation of a limited volume of ethanol is effective
      for the treatment of symptomatic hepatic cysts and potentially reduces the
      incidence of complications.

PMID- 16001650
TI  - Immunohistochemical study of hepatic angiomyolipoma.
AB  - BACKGROUND/AIMS: Angiomyolipoma (AML), a rare benign tumor, occurs in the liver
      and other organs. The hormonal role in genesis and development of HAML is
      unknown. We performed an immunohistochemical study on 12 female cases to detect
      estrogen and progesterone receptors (ER, PR) to elucidate the hormonal role in
      this tumor. METHODOLOGY: Medical records of the 12 patients with hepatic
      angiomyolipoma (HAML) treated at the Chang Gung Memorial Hospital-Taipei between
      Oct 1988 and Oct 2000 were retrospectively reviewed. An immunohistochemical study
      was performed on these twelve patients with ER, PR, and HMB-45. RESULTS: Twelve
      female patients with HAML were identified with ages ranging from 28 to 66 years.
      Abdominal pain was the most frequent symptom. HMB-45 was positive in all the
      twelve patients. ER and PR were negative in all cases. CONCLUSIONS: HMB-45
      special staining could be regarded as a diagnostic criterion for HAML. Sex
      hormone may play no role in the pathogenesis and growth of the HAML. Hormonal
      therapy also plays no role in the management of the tumor. Its prognosis is
      favorable regardless of management.

PMID- 16001651
TI  - Effect of interferon on incidence of hepatocellular carcinoma in patients with
      chronic hepatitis C.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate whether IFN prevents the
      development of HCC in patients with chronic hepatitis C. METHODOLOGY: 103
      patients with chronic hepatitis C received IFN and 30 control patients were
      enrolled in this study. RESULTS: In 33 patients (32.0%) who received IFN, alanine
      aminotransferase (ALT) decreased to normal range and HCV RNA became negative
      (complete response: CR). In 7 patients (6.7%), ALT decreased to less than 50 IU/L
      or stayed within the normal range, but HCV RNA remained positive (biochemical
      response: BR). In 63 patients (61.1%) and 30 control patients, ALT did not change
      and HCV RNA remained positive (no response: NR). HCC developed in 5 (4.9%) of the
      103 patients who received IFN and 7 (23.3%) of the control patients (p<0.01). In
      5 patients who developed HCC, the response to IFN was NR and no HCC developed in
      patients with CR or BR. In addition, 5-year cumulative rate of development of HCC
      in 63 IFN NR patients and in control was 7.9% and 23.3% (p<0.05). CONCLUSIONS:
      IFN decreased the development of HCC in not only patients with CR or BR but also
      patients with NR.

PMID- 16001652
TI  - Hepatocellular carcinoma and hepatitis C in Mexico.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has increased in many countries
      as a result of an increased frequency of hepatitis C virus (HCV) infection. In
      Mexico, the association of HCC to HCV infection has not been evaluated. This
      study aims to evaluate the epidemiological factors related to HCC in Mexican
      patients as well as the results of treatment. METHODOLOGY: A retrospective review
      of clinical files of patients with HCC diagnosed between May 1992 to July 2002
      was performed. RESULTS: There were 63 males and 64 females with a median age of
      57 years (range 17-82). Seventy-one patients were evaluated for hepatitis status.
      In 43 (60%) HCV was the etiological factor. Isolated HCV infection was present in
      32 (45%), HCV infection and ethanol abuse was observed in 11 (15.5%). In six
      (8.4%) patients hepatitis B was the etiological factor. HCV and HBV infection
      were found in 9 (12.6%). HCV and HBV infection associated to ethanol abuse was
      present in one patient. Ethanol abuse alone was observed in six (8.4%) patients.
      The median size of the lesion was 8cm (range 3-20cm). Alpha-fetoprotein was
      measured in 113 patients and was higher than 500ng/dL in 60 (53%). Sixty-five
      patients received supportive measures. Sixty-two were treated. Eighteen were
      resected. Thirteen were treated with intraoperative large volume ethanol
      injection (ILVEI), 12 with chemotherapy and 19 with tamoxifen-talidomide.
      Patients without treatment had a median survival time of 11 months and patients
      who received treatment had a median survival time of 25.3 months. The median
      survival time in patients who received surgery was 26 months, the ILVEI group
      survival time was 18 months, the chemotherapy survival was 8.8 months, and the
      tamoxifen-talidomide survival time was 7 months. CONCLUSIONS: HCC is a rare
      neoplasm in Mexico and HCV infection is the main etiological factor. Surgical
      resection is the best form of treatment of HCC in our country. However, only 14%
      of the patients were candidates. For non-resectable lesions, ILVEI offers the
      best palliative results in our center.

PMID- 16001653
TI  - Clinicopathologic features and prognostic factors of resected solitary small
      sized hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Solitary small-sized HCCs tend to be considered as less
      aggressive cancer, and non-surgical treatments have recently been preferred. The
      aim of this study was to clarify the clinicopathological features and the
      prognostic factors of small-sized HCCs and to evaluate the significance of
      hepatic resection for them. METHODOLOGY: Eighty patients with HCC up to 2cm in
      diameter who had undergone hepatic resection were enrolled in this study. We
      investigated the clinicopathological features and evaluated the prognostic
      factors by univariate and multivariate analyses. RESULTS: The overall survival
      rates at 3, 5 and 10 years were 83%, 69% and 36%, respectively, and the
      corresponding disease-free survival rates were 63%, 41% and 10%. Well
      differentiated, moderately differentiated and poorly differentiated HCC were
      detected in 29%, 65% and 6% of the patients, respectively. Furthermore,
      microscopic portal vein invasion (vp), hepatic vein invasion (vv) and
      intrahepatic metastasis (im) were positive in 15%, 4% and 10% of the patients,
      respectively. Multivariate analysis revealed that Child-Pugh classification
      (p=0.005) and vp (p=0.0008) were independent prognostic factors for survival rate
      and that platelet count (p=0.002) and tumor differentiation (p=0.0016) were
      independent prognostic factors for disease-free survival rate. CONCLUSIONS: Even
      solitary small-sized (up to 2cm in diameter) HCC already have the characteristics
      of advanced HCC. When hepatic function is well preserved, hepatic resection
      should be the first choice for local control, especially in cases of moderately
      to poorly differentiated HCC, because the frequency of microscopic vascular
      invasion is high.

PMID- 16001654
TI  - Risk factors associated with bile leakage after hepatic resection for
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Bile leakage after hepatic resection can cause septic
      complications and mortality. This study evaluated the risk factors associated
      with postoperative bile leakage in hepatocellular carcinoma patients.
      METHODOLOGY: Between July 1991 and December 2000, 605 consecutive hepatocellular
      carcinoma patients who underwent hepatic resection were enrolled. Risk factors
      associated with postoperative bile leakage were examined, with 38
      clinicopathological variables being analyzed. Data were collected prospectively
      and analyzed retrospectively. RESULTS: Bile leakage developed in 35 (5.8%) of 605
      patients. When compared with patients without bile leakage, those with bile
      leakage had higher risk for concomitant morbidities (54.3% vs. 29.2%, P=0.002),
      postoperative mortality (8.6% vs. 2.6%, P=0.045), and a prolonged postoperative
      hospital stay (29 days vs. 14 days, P<0.001). The bile leakage rate of centrally
      located tumors (9.4%) was significantly higher than that of peripherally located
      tumors (3.5%; P=0.002). The bile leakage rate of patients with preoperative
      chemoembolization (13.8%) was significantly higher than those without
      chemoembolization (4.9%; P=0.004). Stepwise logistic regression analysis
      identified preoperative chemoembolization (OR=3.274, P=0.005) and tumor(s) being
      centrally located (OR=2.927, P=0.003) as the independent predictors of
      development of bile leakage. CONCLUSIONS: For HCC patients, preoperative
      chemoembolization and tumor(s) with central location are risk factors for post
      hepatectomy bile leakage. As bile leakage can cause septic complications and
      liver failure, careful surgical procedures and use of preventive measures are
      necessary, especially in patients with high risk factors.

PMID- 16001655
TI  - Extended cold preservation of the graft liver enhances neutrophil-mediated
      pulmonary injury after liver transplantation.
AB  - BACKGROUND/AIMS: The precise mechanisms of pulmonary injury after liver
      transplantation, especially those associated with cold ischemia time, are not yet
      clear. METHODOLOGY: We histologically evaluated the number of accumulated
      polymorphonuclear neutrophils (PMNs) in lungs, and pulmonary injury after liver
      transplantation with varying periods of cold ischemia (1, 6 and 24h in University
      of Wisconsin solution at 4 degrees C). Pulmonary expression of cytokine-induced
      neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2)
      mRNA were investigated by quantitative reverse-transcription polymerase chain
      reaction. The levels of tumor necrosis factor-alpha (TNFalpha), which stimulates
      these chemokine productions, were also monitored after liver transplantation.
      RESULTS: The accumulated PMN number, and lung edema, quantified by wet to dry
      weight ratio, significantly increased in the 24-hr cold-ischemia group after 3h
      of reperfusion, compared with the 1-hr and 6-hr cold-ischemia groups. Both
      pulmonary MIP-2 and CINC mRNA expression in the 24-hr group were remarkably
      upregulated at this time. According to the histological examination, pulmonary
      injury in the 24-hr group was prominent, characterized by interstitial edema, and
      alveolar hemorrhage. Furthermore, TNF in the hepatic vein was detected only in
      the 24-hr group. CONCLUSIONS: Cold ischemia time prolongation upregulates
      pulmonary MIP-2 and CINC expression via hepatic-derived TNFalpha, and promotes
      PMN accumulation, resulting in increased pulmonary injury after liver
      transplantation.

PMID- 16001656
TI  - p53 protein expression in chronic hepatitis C; effect of interferon alpha 2b
      therapy.
AB  - BACKGROUND/AIMS: Gene p53 plays an important role in apoptosis or regeneration of
      damaged tissues. HCV activates gene p53 directly and/or indirectly. In chronic
      hepatitis, hepatocyte regeneration is regulated by gene p53 and growth factors.
      The aim of the study was the evaluation of protein p53 expression on hepatocytes
      in chronic hepatitis C regarding inflammatory activity and fibrosis as well as
      the influence of interferon alpha 2b (IFNalpha2b) on gene p53 activity.
      METHODOLOGY: In 24 patients with chronic hepatitis C treated with IFNalpha2b
      (18MU sc/week/48 weeks), in whom liver biopsies were performed before and after
      IFNalpha2b treatment. The immunohistochemical method determined protein p53 in
      formalin-fixed, paraffin-embedded liver tissue sections. The percentage of p53
      positive hepatocytes and intensity of protein p53 accumulation were evaluated
      under a light microscope. RESULTS: IFN treatment caused the increase in the
      percentage of p53-positive hepatocytes and the intensity of protein p53
      accumulation. The highest level of protein p53 expression was observed in
      IFNalpha2b-treated tissues with the decrease in inflammatory activity and
      fibrosis. HCV infection elimination did not affect protein p53 expression. We
      observed the decrease in p53-positive hepatocytes in tissues without improvement
      of morphological regeneration during IFNalpha2b therapy. CONCLUSIONS: The
      increase in protein p53 expression can be considered a prognostic marker of the
      positive effect of IFNalpha2b treatment and HCV elimination. It may result from
      the effect of the increase in regeneration or apoptosis of HCV infected
      hepatocytes.

PMID- 16001657
TI  - Clinical outcome of 214 liver resections using microwave tissue coagulation.
AB  - BACKGROUND/AIMS: Liver resection is the most effective form of treatment for
      patients with hepatocellular carcinoma. The use of a microwave tissue coagulator
      has been reported to enable limited liver resections for the patients with poor
      hepatic reserve. Herein, we report the clinical outcome of 214 patients with HCC
      who underwent non-anatomical liver resection using MTC in accordance with the
      tumor size. METHODOLOGY: A consecutive series of 214 patients who underwent liver
      resections using MTC were observed over a 10-year study period. The clinical
      characteristics of patients were evaluated. The operative mortality and
      morbidity, overall patient survival and disease-free survival were calculated.
      RESULTS: Seventy-two percent of patients suffered from type C hepatitis and 47%
      of patients had pathologically proven liver cirrhosis. The overall patient
      survival rates were 91, 72, and 58% at 1, 3 and 5 years, respectively. Disease
      free survival rates were 74, 46, and 28% at 1, 3 and 5 years, respectively.
      Postoperative morbidity was 36% and hospital mortality was 2.8%. Complications in
      most patients were well controlled. CONCLUSIONS: Non-anatomical liver resections
      using MTC, in accordance with tumor sizes, can be achieved safely with acceptable
      results and without the need to use special techniques.

PMID- 16001658
TI  - Up-regulation expression of MLC1 in human liver cancer tissue and enhanced
      SMMC7721 cell tumorigenesis in vivo and vitro.
AB  - BACKGROUND/AIMS: We screened a novel gene MLC1 in human liver cancer tissue by
      differential display, and its cDNA full-length is 1600bp. The purpose of this
      study is to find expression of MLC1 gene in human liver cancer tissue and the
      affect to SMMC7721 cell tumorigenesis in vivo and vitro. METHODOLOGY: 250 cases
      of primary HCC tissue samples were studied for MLC1 mRNA and protein expression
      using RT-PCR, western blot, immunohistochemistry, MLC1 stable transfection into
      SMMC771, and SMMC7721 cells growth curve was analyzed by MTT method and SMMC7721
      cells tumorigenesis in vivo. RESULTS: RT-PCR results showed that 98.1% (245/250)
      was MLC1 up-regulation expression, 1.9% (5/250) was MLC1 down-regulation
      (p<0.01). Immunohistochemistry showed that 97.2% (243/250) was MLC1 up-regulation
      expression, 2.8% (7/250) was down-regulation (p<0.01) in cancer tissue compared
      with paracancerous tissue (p<0.01). Western blotting results showed that 98.9%
      (247/250) was MLC1 up-regulation expression, 1.1% (3/250) was MLC1 down
      regulation. Overexpression of MLC1 enhanced the growth of SMMC7721 cells compared
      with the control cells. pcDNA3.1-MLC1 cells accelerated tumor formation compared
      with pcDNA3.1. CONCLUSIONS: MLC1 gene showed up-regulation expression at both the
      mRNA and protein levels in HCC tissues and that MLC1 plays an important role in
      the growth of hepatoma cell SMMC7721 in vitro and vivo.

PMID- 16001659
TI  - Effect of interferon, ribavirin and ursodeoxycholic acid in patients with
      hepatitis C infection.
AB  - BACKGROUND/AIMS: Combination therapy of interferon-alpha (IFNalpha) and the oral
      nucleoside analog, ribavirin is the standard treatment for individuals suffering
      from hepatitis C virus (HCV) infection. Several studies have shown combination
      therapy of IFN and antioxidants is therapeutically beneficial in these patients.
      Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid possessing antioxidant
      properties. This study evaluated the clinical outcome and extent of oxidative
      stress in a group of non-responding and disease-relapsed HCV patients treated
      with IFNalpha, ribavirin and UDCA (triple therapy) for 6 months. METHODOLOGY:
      Twenty patients with chronic HCV disease were treated with triple therapy for six
      months. During this period, they were monitored for the presence of HCV RNA,
      standard serum parameters of liver function and the plasma levels of lipid
      peroxides (LP) and glutathione (GSH) as indices of oxidative stress. The patients
      were reassessed six months after completion of treatment. RESULTS: During the 6
      month treatment period, the health status of the patients improved reflected by
      falls in the serum activities of alanine and aspartate aminotransferases and
      gamma-glutamyl transpeptidase and an initial lowering of viral (HCV RNA) load.
      Six months after cessation of treatment, the patients showed biochemical and
      virological evidence of disease relapse. The elevated plasma LP levels normalized
      during the treatment period and remained within normal levels 6 months after
      completion of treatment. Plasma GSH levels fluctuated within the normal range
      over the 12-month observation period. CONCLUSIONS: Treatment of individuals with
      chronic HCV hepatitis with triple therapy comprising IFNalpha, ribavirin and UDCA
      improves the health status, as well as lowering the extent of oxidative stress in
      these individuals. This treatment regimen also resulted in a sustained lowering
      of plasma lipid peroxide levels in the face of laboratory evidence of disease
      relapse. This preliminary study is unable to provide an apt explanation for the
      persistence of normal plasma LP levels in the face of evidence of disease relapse
      6 months after completion of treatment. However, we believe these preliminary
      findings are sufficiently intriguing to warrant further study. Such
      investigations should include more patients with assessment of the extent of
      hepatic fibrosis during and after completion of treatment to determine whether
      this treatment can modify the natural progress of the disease.

PMID- 16001660
TI  - Immune thrombocytopenic purpura in patients with hepatitis C virus infection.
AB  - BACKGROUND/AIMS: Immune thrombocytopenic purpura could occur as an extrahepatic
      manifestation of hepatitis C virus infection. The aim of this study was to
      clinically analyze hepatitis C virus-positive cases with immune thrombocytopenic
      purpura and to examine the relationship between hepatitis C virus and immune
      thrombocytopenic purpura. METHODOLOGY: Eight hepatitis C virus-positive patients
      with immune thrombocytopenic purpura were compared with 67 cases with chronic
      hepatitis C without immune thrombocytopenic purpura. We examined various clinical
      and hematological parameters including platelet and platelet-associated
      immunoglobulin G. RESULTS: Two men and 6 women with hepatitis C virus infection
      (age 58.0 +/- 11.8) were diagnosed with immune thrombocytopenic purpura. Platelet
      counts (x10(4)/mm3) were significantly lower in these 8 patients (2.9 +/- 2.1)
      than in chronic hepatitis C patients without immune thrombocytopenic purpura
      (16.7 +/- 0.3) (P<0.001). Hepatitis C virus infection predated immune
      thrombocytopenic purpura in 6 patients and none of the patients with immune
      thrombocytopenic purpura was infected with hepatitis C virus after the diagnosis.
      Three of the 6 patients with chronic hepatitis C, which predated immune
      thrombocytopenic purpura, were treated with interferon and 2 developed immune
      thrombocytopenic purpura after the treatment. None of them eradicated hepatitis C
      virus by interferon. CONCLUSIONS: The fact that hepatitis C virus infection
      predated immune thrombocytopenic purpura in 6 of 8 patients suggests that
      hepatitis C virus could potentially induce immune thrombocytopenic purpura and
      interferon itself might induce immune thrombocytopenic purpura.

PMID- 16001661
TI  - Sclerosing hepatocellular carcinoma: clinicopathologic features in seven patients
      from Taiwan and review of the literature.
AB  - BACKGROUND/AIMS: Sclerosing hepatocellular carcinoma (HCC) is an uncommon subtype
      of HCC. We provided data on 7 cases of sclerosing HCC, including clinical
      presentations, diagnoses, management, and prognoses. METHODOLOGY: A retrospective
      review of the medical records of seven patients with sclerosing HCC treated at
      Chang Gung Memorial Hospital-Taipei between Oct 1994 and Jan 2001. RESULTS: Seven
      patients with sclerosing HCC were identified, with ages ranging from 26 to 71
      years (mean, 42.3 years). Abdominal fullness was the most common symptom,
      occurring in 4 of seven patients (57.1%). All seven patients with sclerosing HCC
      had normal serum calcium and phosphate values. HCC was the most common
      preoperative diagnosis, occurring in 5 of seven patients (71.4%). Three of the
      seven patients were correctly diagnosed with sclerosing HCC preoperatively. The
      median overall survival and disease-free survival of these seven patients were 20
      and 9 months, respectively. CONCLUSIONS: In Taiwan, the patients with sclerosing
      HCC had normal serum values of calcium and phosphate. Sclerosing HCC has
      specific, but different radiological and pathological features, compared with
      conventional HCC. Its prognosis does not seem poor, although we still need to
      follow-up for a longer period.

PMID- 16001662
TI  - Bilirubin level fluctuation in drain discharge after hepatectomies justifies long
      term drain maintenance.
AB  - BACKGROUND/AIMS: Need for abdominal drains after liver resection is debated.
      However, unrecognized bile leak is relatively frequent: to prevent bile
      collection we adopted the use of long-term drains. The aim of this study was to
      validate this policy checking the bilirubin concentration in the drain discharge
      and serum along the postoperative course. METHODOLOGY: A prospective cohort study
      enrolling 58 consecutive patients with liver tumors was carried out. All patients
      underwent liver resection and received abdominal drains which were maintained for
      at least 7 days postoperatively. The bilirubin concentration in serum and drain
      discharge was sampled on the 3rd, 5th and 7th postoperative days. RESULTS: No
      postoperative mortality and major morbidity were observed. The bilirubin level in
      drain discharge was higher on the 5th postoperative day than on the 3rd and 7th
      postoperative days: difference between the 3rd and 5th postoperative days was
      significant. No differences were observed among serum bilirubin levels on 3rd,
      5th and 7th postoperative days. CONCLUSIONS: The bilirubin level in drain
      discharge increases late in the postoperative course. Therefore, bile leakage
      should be evaluated between the 5th and 7th postoperative days. The use of long
      term drains helps protect against undiscovered collections and thus impacts
      postoperative course.

PMID- 16001663
TI  - Liver functional analysis by total bile acid level of C-tube bile after
      hepatectomy.
AB  - BACKGROUND/AIMS: In order to predict liver failure which can lead to death after
      hepatectomy, a sensitive and specific indicator is needed for liver function.
      Transcystic duct tube (C-tube) drainage after hepatectomy is thought to be useful
      in decreasing postoperative complications. METHODOLOGY: Conventional serum liver
      function tests, and total bile acid (TBA) and total bilirubin (T.Bil)
      concentration levels of bile from a C-tube in 11 hepatectomized patients who
      underwent C-tube drainage were compared on postoperative day 2 (Day 2) and
      postoperative day 7 (Day 7). RESULTS: When serum liver function tests were
      improving between Day 2 and Day 7, the TBA concentration in bile was increasing
      in contrast to a decreasing T.Bil concentration. On Day 7, TBA concentrations in
      the bile in patients without liver cirrhosis or with low ICGR15 values were
      higher than those in patients with liver cirrhosis or with high ICGR15 values,
      whereas there were no significant differences between T.Bil bile concentrations
      in the two groups on Day 7, that is, the measurement of TBA bile concentration
      might be a faster and more accurate parameter for liver function than that of
      T.Bil bile concentration. CONCLUSIONS: TBA bile concentration obtained from C
      tubes was a useful liver function indicator after hepatectomy.

PMID- 16001664
TI  - Extended lobectomy for procurement of the left lobe with caudate lobe for living
      related liver transplantation.
AB  - Liver transplantation from living-related donors has been established for end
      stage liver disease. In adult cases, the left lobe with a caudate lobe was
      transplanted in order to increase the graft volume. However, the procurement
      operation should be less invasive for the donor. In this article, we represent
      our technique by which the blood loss can be reduced during the harvesting
      operation. The technique was used to improve the extended left lobectomy for the
      procurement in 27 patients between May 1997 and December 1999 at Kyushu
      University Hospital. The groups included the following: 1) Procurement operation
      of the extended left lobe with caudate (n=9), 2) without caudate (n=18). The
      detailed record during the operation showed that the mean blood loss and the
      amount for the group with caudate was significantly smaller than that in the
      group without caudate. To reduce the blood loss during the procurement operation,
      we continue to use this technique in the living-related donors for adult
      recipients.

PMID- 16001665
TI  - Primary hepatic carcinoid tumor (a case report).
AB  - A primary hepatic carcinoid tumor arising in a 77-year-old woman is reported. The
      patient was admitted with a huge tumor in the right lobe of the liver and treated
      by an extended right lobectomy of the liver. Light microscopic findings showed
      that the tumor cells had small oval-shaped nuclei and eosinophilic cytoplasm with
      small granules forming trabecular, glandular, and rosette patterns.
      Immunohistochemically, tumor cells were stained positive with neuron-specific
      enolase and synaptophysin and were stained slightly positive with chromogranin
      and carcinoembryonic antigen. Careful examination before and after the operation
      revealed no other origin of the tumor. Based on the findings, the liver tumor was
      diagnosed as a primary carcinoid. The clinical features and diagnosis of this
      rare tumor are discussed in this report.

PMID- 16001666
TI  - Long-term survival following resection of peritoneal implantation from
      hepatocellular carcinoma: a case report.
AB  - This study presents a rare case of long-term survival following the resection of
      peritoneal implantation from hepatocellular carcinoma (HCC). A 33-year-old female
      patient with hepatitis B infection presented with a huge pedunculated HCC and
      underwent left lateral segmentectomy in 1995. She received regular follow-up and
      peritoneal implantation was diagnosed 30 months after hepatic resection using
      abdominal computed tomography due to elevated alpha-fetoprotein (AFP).
      Subsequently, the patient received segmental resection of jejunum and a solitary
      peritoneal implantation from HCC in the mesentery of the jejunum. No peritoneal
      carcinomatosis, direct invasion of the surrounding tissue, or lymph node
      involvement existed and the postoperative course was uneventful. Meanwhile,
      histopathological examination of the resected nodule revealed metastatic
      hepatocellular carcinoma. With regular follow-up with AFP, abdominal
      ultrasonography, and or computed tomography, no intrahepatic tumor recurrence or
      extrahepatic metastasis was observed. The patient survived for 90 months
      following hepatic resection, and survived disease free for 60 months after
      resection of peritoneal implantation from HCC.

PMID- 16001667
TI  - A case of hepatocellular carcinoma (HCC) treated with radiofrequency ablation
      (RFA) using 4D real-time ultrasound system.
AB  - The patient was a 62-year-old man. The anamnesis revealed an alcoholic liver
      disease. The patient was admitted to the department of otolaryngology in our
      hospital with sudden deafness in March 2003. The liver damage was pointed out due
      to the laboratory data on admission. A liver tumor was identified on the
      subsequently performed CT scan and the patient was referred to another department
      at another ward for detailed examinations. Based on the results of contrast
      echography, CT findings and angiography a HCC was diagnosed and RFA was
      performed. The conventional B-mode ultrasound examination sometimes presented
      unclear cross-sectional images of the tumor at the target area, and so additional
      treatment had to be given from time to time. Simultaneously with the puncturing
      multi-slice imaging could be obtained, allowing exact and definite performance of
      the RFA using a 4D real-time ultrasound system. Additionally, ultrasound
      examination with contrast media was conducted to help determine the efficacy of
      treatment.

PMID- 16001668
TI  - A case of metachronous cholangiocellular and hepatocellular carcinoma with good
      prognosis.
AB  - A 63-year-old man was treated for 6 months with interferon (IFN) for chronic
      hepatitis C but the treatment failed to eradicate hepatitis C virus. Six months
      after completion of IFN therapy, cholangiocellular carcinoma (CCC) was detected
      in the posterior inferior segment and was resected surgically. He had been in
      good condition except for diabetic nephropathy progressing to renal failure at 3
      years after the resection of CCC. Seven years after the resection of CCC,
      hepatocellular carcinoma (HCC) was detected in the posterior superior segment of
      the liver. The tumor was pathologically confirmed by fine needle aspiration
      biopsy. The patient was successfully treated with two courses of percutaneous
      ethanol injection and has been well 1 year after the treatment. HCV status did
      not change as genotype 1b with moderate viral load (300 to 500 kilo copies/mL by
      amplicore monitoring) during the follow-up. Thus, even though the patient was
      treated with IFN, hepatitis C could progress to not only HCC but also CCC in the
      same patient. Our patient is still alive, 9.5 years after detection of the first
      tumor.

PMID- 16001669
TI  - Acute-onset autoimmune hepatitis resembling acute hepatitis: a case report and
      review of reported cases.
AB  - We report a 54-year-old Japanese man, whose ALT level was 1689 IU/L, without
      increased gamma-globulin level or autoantibodies. He could not be diagnosed as
      autoimmune hepatitis (AIH) using scoring systems, and his liver function became
      normalized after steroid treatment. Recently, AIH with acute presentation of
      disease and acute-onset AIH without bridging fibrosis have been increasingly
      reported but cases without the character of increasing gamma-globulin level or
      autoantibodies before immunosuppressive treatment are extremely rare. This is the
      third such case report in the literature.

PMID- 16001670
TI  - Unusual endoscopic findings of CMV esophagitis after liver transplantation.
AB  - Cytomegalovirus infections are associated with a high mortality rate after liver
      transplantation, but they are treated successfully by administration of the
      combination of ganciclovir plus intravenous immunoglobulin. We herein describe
      cytomegalovirus esophagitis in a patient having gastrointestinal symptoms such as
      dysphagia, retrosternal pain and epigastralgia after liver transplantation was
      detected by performing the surveillance of endoscopy. At first, the findings of
      endoscopy that were segmental erosive areas but no ulcerative areas on the
      esophageal lumen were unusual in this case of cytomegalovirus infections, but
      cytomegalovirus esophagitis was confirmed by cytomegalovirus immunohistochemical
      stain using biopsies. The patient was treated by ganciclovir at an oral dosage of
      5mg/kg twice a day for 2 weeks. Our experience suggests that cytomegalovirus
      esophagitis should be taken into consideration when a patient has
      gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia
      and has endoscopic findings such as segmental erosions on the esophageal lumen
      despite having no cytomegalovirus-specific endoscopic findings such as ulcerative
      lesions.

PMID- 16001671
TI  - Postoperative infections in cirrhotic patients.
AB  - An overview of the impairments of immune function present and the type as well as
      frequency of infections seen in individuals with advanced liver disease is
      presented. Where data are available, the use of antibiotic prophylaxis to prevent
      these complications is identified. Physicians and surgeons caring for individuals
      with advanced liver disease need to be aware of these issues and be vigilant to
      the recognition, early detection and aggressive treatment of infections in
      patients with advanced liver disease and particularly cirrhosis of any etiology.

PMID- 16001672
TI  - ERT following IORT improves survival of patients with resectable pancreatic
      cancer.
AB  - BACKGROUND/AIMS: The clinical course of patients with pancreatic carcinoma
      remains dismal despite the recent advances of diagnostic and therapeutic
      procedures. One of the main causes is residual carcinoma cells, especially at the
      retroperitoneal aspect after pancreatectomy. Radiation therapy (RT)
      [intraoperative radiation therapy (IORT) and external radiation therapy (ERT)] is
      a therapeutic strategy to conquer the remaining cancer cells. METHODOLOGY:
      Effects of RT were retrospectively examined in 81 patients with pancreatectomy
      for pancreatic cancer together with early and late complications. RESULTS:
      Preoperative clinical data were not different between the RT(+) and RT(-) groups
      excluding peripheral lymphocyte counts. Postoperative early complications equally
      occurred including pancreatic fistula. Regarding late complications (>2 months
      after operation), stomal ulcer, vertebral fracture, pseudoaneurysm,
      intraabdominal hemorrhage, and liver abscess were present only in patients with
      RT. Glucose intolerance tended to be more frequent in the RT (+) group, i.e. 12
      (63%) of the 19 with RT examined and 14 (42%) of the 33 without RT examined.
      Follow-up imaging showed recurrence in 27 (71%) of the 38 patients without RT and
      13 (52%) of the 25 patients with RT. The sites of the recurrence were not
      different by the presence or absence of RT. One-year, 3-year and 5-year
      cumulative survival rates were similar between the RT (-) group (100%, 39%, 21%,
      respectively) and IORT (+) alone group (100%, 29% and 17%, respectively). The
      rates in the IORT (+) and ERT (+) group were 100%, 54% and 28%, respectively,
      which tended to be better than those in the other two groups, but the differences
      were not statistically significant. CONCLUSIONS: These findings suggest that only
      the combination of IORT and ERT somewhat improves the short-term clinical course
      of patients with resectable pancreatic cancer, although there are some RT-related
      late complications. It is recommended that ERT be added to IORT after
      pancreatectomy for pancreatic cancer to improve the clinical course, once IORT
      has been performed.

PMID- 16001674
TI  - Chronic pancreatitis progressing from segmental lesions.
AB  - BACKGROUND/AIMS: Chronic pancreatitis is histologically and functionally a
      progressive disease. To examine the natural history of chronic pancreatitis, we
      evaluated serial pancreatography in cases of chronic pancreatitis, focusing on
      the progression of diffuse-type chronic pancreatitis from the segmental type.
      METHODOLOGY: We reviewed 57 patients with chronic pancreatitis who had undergone
      endoscopic retrograde pancreatography on more than 2 occasions at intervals of at
      least 1 year. Cases of chronic pancreatitis were categorized as diffuse (n=37)
      and segmental (n=20) on the findings of initial endoscopic retrograde
      pancreatography. RESULTS: Twenty-three cases of diffuse-type chronic pancreatitis
      showed progression of pancreatic duct abnormalities. Segmental abnormalities of
      the main pancreatic duct at the body or tail of the pancreas spread to the head
      of the pancreas in 8 cases. Etiologies of these cases of chronic pancreatitis
      were alcoholic, in which patients continued drinking after initial endoscopic
      retrograde pancreatography. In 2 patients who underwent distal pancreatectomy,
      although segmental lesions showed typical histological findings of alcoholic
      chronic pancreatitis, appearances near the margin of these lesions were almost
      normal or indicated slight interlobular fibrosis. CONCLUSIONS: The pancreatic
      tail might represent the site of the initial lesion in some cases of alcoholic
      pancreatitis.

PMID- 16001673
TI  - Low dose dopamine prevents end organ damage in experimentally induced
      pancreatitis.
AB  - BACKGROUND/AIMS: End organ damage due to microcirculatory failure plays an
      important role in the pathogenesis of acute pancreatitis (AP). The aim of this
      study was to investigate whether dopamine, a vasoactive agent, is beneficial in
      the prevention of local and systemic injury in acute pancreatitis. METHODOLOGY:
      Pancreatitis was induced in rats with 5% Na-taurocolic acid infusion into the
      pancreatic duct. Rats were resuscitated for four hours with saline in the
      pancreatitis group (P), lactated ringer's (LR) solution in the LR group and low
      dose dopamine (5 microg/kg/min) + LR in the D-LR group. The sham group (S)
      underwent pancreatic duct cannulation only. Rectal temperature (RT) and
      meanarterial pressure (MAP) were monitored throughout the experiment. Blood
      samples for amylase, lipase, WBC and blood gas analysis were taken at baseline
      and at the end of the study. All rats were sacrificed at the 4th hour and
      pancreatic and lung tissues were removed for histopathological examination and
      tissue myeloperoxidase (MPO) activity. RESULTS: MAP was lower in the P and
      LRgroups than the sham and the D-LR groups. RT was higher in P and LR groups than
      the sham and the D-LR groups. Base deficit was higher in the P group than the
      sham and the D-LR groups. The lung MPO activity was higher in the P group than
      all the others. Lung MPO activity that is closest to the sham was that of D-LR
      group's. The pancreatic MPO activity was found to be increased in the P and
      decreased in the LR groups. CONCLUSIONS: In this experimental model for AP, low
      dose dopamine + LR resuscitation attenuates the lung injury but not the local
      pancreatic injury.

PMID- 16001676
TI  - The role of surgery in pancreatic pseudocyst.
AB  - BACKGROUND/AIMS: Surgery has been the only option available for many years for
      treating pseudocyst of the pancreas. Recently, new methods, such as percutaneous
      drainage, endoscopic transenteric drainage and transpapillary drainage, began to
      be used for treatment of the pseudocyst. But we have to agree that no single
      technique offers the desired combination of 100% success and no complications.
      We'd like to present our surgical experience in the past 14 years. METHODOLOGY: A
      total of 22 patients were treated for pancreatic pseudocyst (PP) in our
      departments in Dalin and Hualien Tzu-Chi General Hospital within the last 14
      years. They were retrospectively reviewed and followed up until recently.
      RESULTS: There were 14 (63.6%) males and 8 (36.4%) females aged between 15 and 79
      years old (mean age 38.2 years). Dominating symptoms in most patients were
      epigastric pain, palpable mass, nausea, vomiting, fever and leukocytosis, and
      persistent elevation of serum amylase. Imaging studies, such as ultrasound,
      computed tomography (CT) scan, and endoscopic retrograde cholangiopancreatography
      (ERCP), were helpful in establishing diagnosis. In addition to symptomatic
      persistent large (>6cm) pseudocyst, various types of complication including
      infection, gastrointestinal (GI) obstruction, rupture into GI tract, peritonitis,
      GI bleeding, internal bleeding, and pancreatic ascites were indications for
      surgery in our cases. Operative procedures composed of external drainage (ED, 9
      cases), internal drainage using cystojejunostomy (CJ, 4 cases) and
      cystogastrostomy (CG, 8 cases), and distal pancreatectomy (1 case). Ten
      complications (45.5%) included recurrence of cyst (1 in-ED and 1 in CJ),
      recurrence with pancreaticopleural fistula (1 in ED), colon perforation (1 in
      ED), delayed massive bleeding (1 in CG), pancreatic fistula (3 in ED), pancreatic
      abscess (1 in CJ) and persistent pain (1 in CG). Reoperation was needed to check
      bleeding (1 in CG) and proximal colostomy for colon injury (1 in ED). A case
      received CJ for recurrence of pseudocyst 9 years later (1 in CJ). Percutaneous
      drainage with wide bore tube was effective for pancreatic abscess (1 in CJ) and
      transpapillary drainage with stent was used to relieve pleural effusion with
      respiratory failure (1 in ED). No mortality occurred in this series. CONCLUSIONS:
      We believe that surgery, though without flaws, still plays an important role in
      the management of selected cases of pseudocyst of the pancreas. Surgical
      intervention, endoscopic drainage, and percutaneous drainage were complementary
      rather than conflicting alternatives both for the simple and complicated
      pseudocysts.

PMID- 16001675
TI  - VIPomas: an update in diagnosis and management in a series of 11 patients.
AB  - BACKGROUND/AIMS: VIPoma is a rare pancreatic endocrine tumor (PET) which secretes
      excessive amounts of VIP (Vasoactive Intestinal Peptide) that causes a special
      clinical syndrome characterized by secretory diarrhea, hypokalemia and
      achlorhydria. Among a total number of 76 patients (pts) with PETs, we present in
      this study 11 pts with VIPoma syndrome focusing on our diagnostic and therapeutic
      approach, in parallel with a brief review of the literature. METHODOLOGY: Eleven
      pts (7 males and 4 females), aged from 2 to 83 years (mean age 53.1 years) were
      included. The diagnosis was based upon compatible clinical features and serum VIP
      values and was supported by the estimation of other peptides and neuroendocrine
      markers such as gastrin, pancreatic polypeptide and chromogranin-A (CgA). In
      10/11 pts, diagnosis was confirmed histopathologically. The primary or metastatic
      lesions were located by conventional imaging methods or by OCTREOSCAN or
      Endoscopic Ultrasound (EUS). The follow-up period ranged from 2.5-13.5 years
      (mean 4.8 years). RESULTS: Chronic secretory diarrhea, which persisted despite
      fasting, was the main symptom in all pts of our study. VIP levels at the time of
      diagnosis were more than 3 or 10 times the upper normal limit in 7/11 (63.6%) or
      4/11 (36.4%) pts, respectively. The primary lesion was detected by CT scan or MRI
      in 6/11 (54.5%), with EUS or abdominal angiography in 4/11 (36.4%). OCTREOSCAN
      revealed a solitary lesion in the right hepatic lobe, not detected by all the
      previous studies, while it detected, as a whole, the primary lesion in 10/11
      (91%), and the metastases in 3/4 (75%) pts. In 7/11 (63.6%) the primary lesion
      was located in the pancreas, whereas in the rest it was in the duodenum or
      retroperitoneum. A surgical resection was possible in 7/11 (63.6%) pts, while pts
      with metastatic disease already or poorly differentiated tumors also received
      additional treatment with somatostatin analogues and chemotherapy. Liver
      metastases and poor differentiation of tumors seemed to be negative prognostic
      factors. CONCLUSIONS: Clinical suspicion, early diagnosis and precise management
      may affect survival and improve the quality of life of patients. Also, surgical
      treatment, as extensive as possible, in combination with somatostatin analogues
      or chemotherapy when necessary, may also result in prolonged survival, also in
      patients with advanced disease.

PMID- 16001677
TI  - Alcoholic chronic pancreatitis with simultaneous multiple severe complications-
      extrahepatic portal obliteration, obstructive jaundice and duodenal stricture.
AB  - The major complications of chronic pancreatitis are malabsorption, diabetes
      mellitus, pancreatic calcification and pseudocysts. Sinistral portal hypertension
      due to splenic vein thrombosis, obstructive jaundice and duodenal stricture have
      also been reported as complications of chronic pancreatitis. However, a case
      having all these three complications at the same time is relatively rare. We
      present a case of chronic alcoholic pancreatitis complicated with simultaneous
      multiple severe complications. Although biliary drainage is usually a useful
      treatment for reducing the bilirubin level in the patients with obstructive
      jaundice, jaundice was hardly improved by the percutaneous transhepatic cholangio
      drainage (PTCD) in this case. We discussed the cause of the failure in reducing
      the jaundice and reviewed the previous reports of complications of pancreatitis.

PMID- 16001678
TI  - Solitary pancreas metastasis from AFP-producing gastric cancer: report of a case.
AB  - We herein present a case of resected pancreatic metachronous metastasis arising
      from alpha-fetoprotein-producing gastric cancer. A 75-year-old man underwent
      distal gastrectomy for alpha-fetoprotein-producing gastric cancer in November
      1999. The staging group of TNM classification was Stage IIIA. The serum AFP level
      normalized after surgical resection. During the follow-up period, it increased to
      42ng/mL in January 2002, and up to 550ng/mL in July 2002: Abdominal computed
      tomography disclosed a 4-cm mass in the tail of the pancreas and under the
      diagnosis of pancreas metastasis, distal pancreatectomy with splenectomy was
      performed. Following this, serum alpha-fetoprotein declined to 61ng/mL, and the
      postoperative course was uneventful. But it elevated again to 200ng/mL in August,
      and to 3500ng/mL in September 2002. Computed tomography revealed multiple liver
      metastases. He was treated with TS-1, but hepatic lesions continued to grow and
      he died in March 2003. To our knowledge, this case is the first report of
      resection of solitary pancreas metastasis of alpha-fetoprotein-producing gastric
      cancer.

PMID- 16001679
TI  - Adenocarcinoma of the pancreas--past, present and future.
AB  - Adenocarcinoma of the pancreas has always been a disease with a dismal prognosis.
      Almost every patient with this cancer dies of the tumor. Over the years there has
      been extensive advancement in the understanding of etiology, molecular biology,
      diagnosis and treatment of this disease. Presently, surgical resection is the
      only potentially curative option available for these patients. It is now clear
      that surgery alone cannot increase the survival of these patients. With the
      understanding of molecular biology of pancreatic cancer new management strategies
      are under a preclinical stage of development. These new diagnostic and
      therapeutic modalities hopefully will improve the outcome of patients with
      pancreatic cancer.

PMID- 16001681
TI  - Gastrointestinal stromal tumor of the stomach: report of a case.
AB  - We report herein a case of a 65-year-old woman who had a gastrointestinal stromal
      tumor (GIST) of the stomach. Preoperative endoscopic and X-ray examinations
      showed a spherical submucosal tumor in the gastric fornix. We resected the tumor
      by laparoscopic surgery, because it was detected by computed tomography (CT) and
      positron emission tomography (PET), and they did not detect distant metastasis.
      Postoperative histologic examination revealed that the tumor was composed of
      spindle-shaped cells with elongated nuclei and showed little mitosis. Almost all
      of the cells showed immunoreactivity for c-kit, CD34, vimentin and but did not
      show alpha-smooth muscle actin (SMA), S-100, or desmin. The Ki-67 labeling index
      was 0.8%. The tumor did not show differentiation toward smooth muscle or neural
      cells. Pathological findings showed this tumor was probably benign. In such
      cases, careful follow-up is needed to detect liver metastasis and local
      recurrence.

PMID- 16001680
TI  - Comparison of serum aberrant methylation and conventional tumor markers in
      gastric cancer patients.
AB  - BACKGROUND/AIMS: This study was designed to compare a methylation-specific
      polymerase chain reaction (MSP) assay for three genes [p16, E-cadherin, and
      retinoic acid receptor beta (RARbeta)] and conventional serum tumor markers using
      blood samples from gastric cancer patients. METHODOLOGY: Preoperative blood
      samples obtained from 63 consecutive patients with gastric cancer were subjected
      to MSP and conventional serum marker assays. RESULTS: MSP assay detected
      hypermethylation of p16 in 17 patients (27%), E-cadherin in 15 patients (24%),
      and RARbeta in 11 patients (17%). Altogether, 32 patients (51%) showed
      hypermethylation in serum samples. By contrast, only 21 (33%) patients exhibited
      elevations of serum carcinoembryonic antigen or carbohydrate antigen 19-9. There
      was no correlation between MSP results and conventional tumor markers.
      CONCLUSIONS: The detection rate for MSP was higher than that of conventional
      tumor markers in serum of gastric cancer patients. Both assays can serve as
      complementary markers that allow for selection of cases requiring more intensive
      screening or aggressive postoperative treatment.

PMID- 16001682
TI  - En bloc endoscopic mucosal resection of a large early stage gastric cancer by
      combined use of an insulation-tipped diathermic knife and a grasping forceps
      percutaneously inserted into the gastric lumen.
AB  - A new endoscopic mucosal resection using an insulation-tipped diathermic knife
      (IT knife-EMR) is a promising procedure for en bloc resection of an early stage
      gastric cancer. However, the use of this procedure for a large lesion on the
      greater curvature of the gastric middle-upper body is technically difficult. With
      the help of a grasping forceps percutaneously inserted into the gastric lumen,
      which allowed traction to be applied to the lesion, a 66-year-old man with a
      large tumor (49mm in diameter) on the greater curvature of the gastric middle
      body underwent IT knife-EMR. This approach enabled easy dissection between the
      submucosa and the muscle layer by the IT knife under direct vision. The lesion
      was completely removed as a single piece. This new technique, employing IT knife
      EMR in cooperation with a percutaneously inserted grasping forceps, could be a
      potential procedure to make original IT knife-EMR easier. This approach may
      enhance the utility of original IT knife-EMR for selected tumors, that is, large
      tumors on the greater curvature of the middle-upper body of the stomach and/or
      ulcerated tumors. We propose that the present approach may provide an important
      alternative to laparoscopic intragastric surgery.

PMID- 16001683
TI  - New concepts of molecular biology on gastric carcinogenesis.
AB  - Gastric cancer not located in the cardia still remains the second most common
      cancer worldwide, whereas adenocarcinoma of the cardia and gastroesophageal
      junction has been rapidly rising over the past two decades. Gastric cancer can be
      subdivided into two distinct pathologic entities, diffuse and intestinal, that
      have different epidemiologic and prognostic features. Various genetic and
      environmental factors play important roles in gastric carcinogenesis; both lead
      to either abnormal genes overexpression or inappropriate expression of normal
      genes, whose products confer the malignant phenotype. Advances have been made in
      the genetic changes mostly of the intestinal type; its development is probably a
      multistep process, as has been well described in colon cancer pathogenesis,
      whereas it remains tentative whether the diffuse type of malignancy follows an
      analogous progression. The most common genetic abnormalities in gastric cancer
      tend to be loss of heterozygosity of tumor suppressor genes, particularly of p53
      or "Adenomatous Polyposis Coli" gene. The latter leads to gastric oncogenesis
      through changes related to E-cadherin-catenin complex, which plays a critical
      role in the maintenance of normal tissue architecture. Mutation of any of its
      components results in loss of cell-cell adhesion, thereby contributing to
      neoplasia. E-cadherin/CDH1 gene germline mutations have been recognized in
      families with an inherited predisposition to gastric cancer of the diffuse type.
      Amplification and/or overexpression of putative trophic factors have also been
      observed in gastric cancer. Finally, Helicobacter pylori (H. pylori) infection is
      also involved in gastric carcinogenesis through various mechanisms, thereby
      necessitating H. pylori eradication in patients with gastric cancer.

PMID- 16001684
TI  - The effect of compressive cyclic loading on retention of a temporary cement used
      with implants.
AB  - Masticatory forces cause fatigue to cement-retained crowns and abutments and may
      adversely effect retention. The relation between the number of load cycles and
      the retentive forces is important. This study evaluated the effect of compressive
      cyclic loading on the retentive forces of a temporary cement used to retain
      implant crowns and the relationship between load cycles and retentive forces. Ten
      castings and implant abutments were cemented with zinc oxide-eugenol temporary
      cement. The retentive force necessary to dislodge the casting from the abutment
      was determined before and after the application of 2 Hz of vertical off-axis 3-mm
      sinusoidal-type compressive cyclic loading between 20 and 130 N for 500000,
      1000000, and 5000000 cycles. These forces were equivalent to approximately 6
      months, 1 year, and 5 years of human mastication. Data before and after the
      applied loading were analyzed with a paired sample t test (alpha = 0.05). The
      retentive forces of the 3 groups were analyzed by 1-way analysis of variance and
      post hoc by Scheffe multiple comparison (alpha = 0.05). The relation of the
      loading and the altered retentive forces were analyzed with the Pearson
      correlation coefficient. Compressive cyclic loading reduced the retentive forces
      significantly in all groups (P = .000). The retentive forces were reduced 16.75%,
      18.73%, and 19.68% during the applied loading cycles of 500000, 1000000, and
      5000000. All reduced retentive forces were not significantly different (P =
      .792). Although cyclic loading reduced the retentive forces, the increased cycles
      had little relationship (R = 0.119) to the decreased retentive forces of the
      temporary cement. The relationship between occlusal loading and retentive force
      can influence the choice of a temporary cement for a particular clinical
      situation.

PMID- 16001685
TI  - Overview of the SwissPlus Implant System.
AB  - Although many improvements have been made to implant dentistry during the last
      quarter of a century, clinical challenges still remain. For the surgeon,
      achieving implant stability in low-density bone can be difficult. For the
      restorative dentist, incompatibility between implant systems and the increasing
      complexity of esthetic restorative options frequently require special training in
      the selection and use of prosthetic components. This article presents an overview
      of a 1-stage implant system with a textured surface and osteocompressive surgical
      protocol designed to achieve stability in soft bone. Self-tapping, double lead
      threads and a separate surgical protocol also enable the implant to be placed in
      high-density bone. The implant is packaged on a fixture mount that also functions
      as a transfer and transitional or definitive abutment for cemented restorations.
      This implant is designed to help simplify restorative procedures by eliminating
      many ancillary restorative components. For multiple-unit, screw-retained
      restorations, the prosthesis can be splinted directly to the top of the implant
      without an intermediate abutment. Overdenture attachments and straight, angled,
      screw-receiving, and custom-cast abutments complete the restorative system.

PMID- 16001687
TI  - The root form universal implant.

PMID- 16001686
TI  - An interim denture technique and case reports.
AB  - An interim denture technique is presented describing the fabrication of an
      esthetic prosthesis that is used for short periods of time. The prosthesis
      conditions the patient for the acceptance of an artificial substitute for missing
      natural teeth until more definitive prosthodontic therapy can be provided. All
      the teeth in the arch are extracted simultaneously, and the interim prosthesis is
      inserted immediately thereafter. The prosthesis duplicates the morphology, color,
      and position of the extracted teeth. This technique satisfies a great need of
      socially and business-active patients because there is no interruption in their
      activities and no change in facial esthetics. Two case histories are presented.

PMID- 16001688
TI  - Key transfer technique for restoring implants with extreme cervix proximity in
      the esthetic zone: a case report.
AB  - Extreme cervix proximity of adjacent implants poses a great challenge to the
      restorative dentist, as accurate transfer of implant analogs to the master cast
      would be difficult to achieve. In this case report, a custom key transfer
      technique was used to precisely duplicate the relation of 2 implants (replacing
      maxillary left central and lateral incisors with severe cervix proximity) from
      the patient's mouth to the master cast. The relation of each implant was
      singularly transferred to a preliminary cast, and then the 2 implant analogs were
      positioned in a master cast for accurate clinical case reproduction. The
      completed master cast allowed for precise fabrication of superstructures that
      accurately fitted the closely related implant cervices in the patient's mouth.

PMID- 16001689
TI  - Bone grifting procedures for osseous defects associated with dental implants.
AB  - The purpose of this study was to clinically and radiographically evaluate the use
      of bone grafting therapy for treatment of osseous defects before implant surgery.
      After bone graft reconstruction, implants may be placed in previous areas of
      osseous defect with the expectation of long-term positive results.

PMID- 16001690
TI  - [The adenoid cystic carcinoma].
AB  - The adenoid cystic carcinoma arising in the external auditory canal is a rare
      tumor, as other malignant neoplasias of the EAC and middle ear. The early
      diagnosis of these malignant tumors of the ear is very important to improve the
      prognosis. In this sense, the clinic experience is frequently the most useful
      diagnosis instrument to suspect this pathology when we have a confrontation with
      chronic otorrea and otalgia, common presentation form of this disease. In this
      report we show a new case of adenoid cystic carcinoma of external auditory canal
      and review the most significant medical literature existing in relationship with
      this pathology.

PMID- 16001691
TI  - [Bibliographic revision of retraction pockets handling in relation to surgical
      treatment].
AB  - There is a great controversy on the actuation on tympanic retraction pockets.
      Some authors back up the theory of carrying out periodic controls and of
      undergoing surgery only in case of more important lesions. Other otologist
      undergo early surgery, because they back up the hypothesis that if the injury is
      incipient, the surgery to carry out is smaller, having more chances of keeping
      the hearing. We revise the literature on the subject: with reference to the
      etiopathogenia of retraction pockets, its relation to cholesteatoma and the
      terapeutic possibilities according to various authors both defendans and
      detractors of surgery. We conclude that periodic otomicroscopy provides early
      diagnosis and control of the atelectasis of the tympanic membrana.

PMID- 16001692
TI  - [Risk factors and clinical variables in patients hospitalized for epistaxis.
      Review of 200 patients].
AB  - It is reported a review of 200 adult patients admitted for epistaxis in our
      Hospital during a 10 years period (1992-2002). This study evaluates several
      factors included in the clinical histories: HTA, infection of the upper airway,
      EPOC, cardiovascular pathology, use of anticoagulant medication or other drugs,
      tobacco, alcohol, diabetes, etc. Besides we collected variables like age, sex,
      bleeding location, type of nasal packing made and evolution. Less than 20% of the
      cases were classified as idiopatic and the hospitalized patients had one or more
      known risk factors.

PMID- 16001693
TI  - [External severe laryngeal trauma with multiple fractures and airway compromise].
AB  - External laryngeal traumas are rare but clinically can cause important life
      threatening injuries. We report the case of a 33 yeras old male who suffered a
      severe traffic accident: TCE, facial trauma with multiple fractures and laryngeal
      trauma with fracture of the thyroid cartilage and the hyoid bone. Because an
      important edema in the airway, it was not possible an orotracheal intubation and
      he required urgent coniotomy with later reconstruction surgery and tracheostomy.
      Actually our patient has been decanulated and the fibroscopic image of the larynx
      and its functionality is correct.

PMID- 16001694
TI  - [Sinonasal cystic adenoid carcinoma with epiphora and orbital involvement. Report
      of a case and review of the literature].
AB  - We report the clinical case of a 41 years old male with nasal obstruction of 1
      year, epistaxis and epiphora. The ENT exam showed a bleeding red mass in left
      nasal fossa and CT joint to IRM revealed a tumoral process on that level and
      informed about its extension to adyacents structures (cavum, ethmoides, sphenoids
      and maxillary sinus). The biopsy was positive for cystic adenoid carcinoma. Our
      patient was operated by paralateronasal rhinotomy with removal of the tumor. One
      year later we found recurrence on the left orbital floor and maxilar sinus. The
      Oncology Department informed that it was not possible a treatment with
      radiotherapy or chemotherapy because the low sensitivity of that lesion those
      treatment.

PMID- 16001695
TI  - Postoperative Ramsay-Hunt syndrome after acoustic neuroma resection. Viral
      reactivation.
AB  - The aim of this paper is to present a patient suffering from acoustic neuroma and
      operated on with immediate postoperative hearing and facial function preservation
      who developed delayed Ramsay-Hunt syndrome. To our knowledge, this is the first
      case in whom a postoperative delayed facial palsy and hearing loss occurred. The
      patient gave an history of previously diagnosed herpes zoster reactivation
      limited to chest one-year before. This is undoubtdetly a predisposing factor for
      development of delayed facial palsy. It must not be underestimated and it obliges
      to consider a prophylaxis. Theoretically, the prophylactic antiviral therapy
      might prevent the evolution towards the herpes zoster oticus or reduce the
      severity of the symptoms allowing the preservation of the hearing function. It
      would be pointed out that the delayed facial plasy has favourable prognosis,
      while the hearing impairment may recover with a greater difficulty even after an
      antiviral treatment as in our case.

PMID- 16001696
TI  - [Cholesterol granuloma in paranasal sinus. An unfrequent pseudotumor in maxillary
      sinuses].
AB  - The cholesterol granuloma is well known in the middle ear, in the mastoid antrum
      and the air cells of temporal bone, mostly related to a chronic infectious
      process. There are other localizations such as the pleura, lung, pericardium,
      kidneys, arterial wall, nerves, brain, testicles, lymphatic ganglion and in the
      paranasals sinuses. Its localization in the mediofacial area is very unfrequent,
      having only been described 44 cases up to the year 2002. We present a 42 year-old
      patient, who required surgical treatment because of a increase in the volume of
      area her left facial of one month's old. It resulted to be secundary to an
      expansion of the maxilar sinus, such as seen on the computerized tomography
      carried out on the patient. The diagnosis was cholesterol granuloma, performed,
      through the anatomo-pathology study. We review the litterature on this subject
      and analyse the possible etiologic cause of this lesion, its clinic, diagnostic
      methodology and treatment.

PMID- 16001697
TI  - Mastoid osteoma.
AB  - Osteoma in the mastoid is a rare benign osteogenic tumour which has been
      described in literature in only 130 cases between 1861 and 2004. It is a
      clinically asymptomatic lesion that usually appears as a tumefaction or
      retroauricular protruding mass. The Authors report 2 cases of mastoid osteoma,
      objectively review the literature on this pathology and present theories on its
      etiopathogenesis, histology, symptomatology and treatment.

PMID- 16001698
TI  - [Inverted nasosinusal papilloma. 11 cases and bibliographic revision].
AB  - INTRODUCTION: We present the cases registred from 1998 to 2003 and a revision of
      the bibliography. MATERIAL AND METHOD: In the section of Rhinology of a second
      level Hospital 11 patients affected by inverted papilloma type 1 of the OMS
      classification were diagnosed aged between 40 and 79, 9 men and 2 women. They
      were explored through endoscopy and biopsy and the exeresis of the lesion was
      done by endoscopic polipectomy with microdebrider (PEM). RESULTS: All the cases
      at stage I, II and III of the Krouse classification. Treated by CEN, 6 by mixed
      endonasal approach and through the canine fossa 4 by nasal approach only and 1 by
      Caldwell-Luc approach. The follow-up was done between 9 to 64 months and there
      was a recidive who was operated by open surgery and no one malignant
      transformation was seen. DISCUSSION: We coment the aspects related to etiology,
      the symptons and the surgical technics. CONCLUSIONS: We propose to stage the
      tumor and the realisation of a PEM with topic anesthesia with deep biopsies in
      all unilateral poly formations to avoid a retarded diagnosis and to be able to
      apply endoscopic technics.

PMID- 16001699
TI  - Controversies in antidepressant therapy.

PMID- 16001700
TI  - Bias in the evaluation of antidepressants.

PMID- 16001701
TI  - Do antidepressants cause dependence?

PMID- 16001702
TI  - The use of Selective Serotonin Re-uptake Inhibitors (SSRIs) in the treatment of
      depressive disorders in children and adolescents.

PMID- 16001703
TI  - Prevalence of mental disorders in the Zurich Cohort Study: a twenty year
      prospective study.
AB  - BACKGROUND: In order to minimise retrospective recall in developing estimates of
      the prevalence of mental disorders in the general population, we conducted a
      prospective study of a cohort of youth from Zurich, Switzerland. METHOD: A 20
      year prospective study of a community-based cohort aged 19-20 from Zurich
      Switzerland. The sample was enriched by subjects scoring high on the Symptom
      Checklist 90 R (Derogatis, 1977). A semi-structured diagnostic interview was
      administered by clinically experienced psychologists and psychiatrists. The six
      interviews from 1979 to 1999 assessed diagnoses and sub-threshold manifestations
      of major diagnostic categories (with the exception of schizophrenia) for the past
      twelve months, depending on the current DSM versions (DSM-III, DSM-III R, DSM
      IV). Additional information on symptoms and treatment were collected for the
      years between the interviews. The reported prevalence rates are weighted for
      stratified sampling and cumulate the one-year rates of the six interviews.
      RESULTS: The cumulative weighted prevalence rates for any psychiatric disorder
      were 48.6% excluding, and 57.7% including tobacco dependence. In addition 29.2%
      and 21.8%, respectively manifested sub-diagnostic syndromes. Overall there were
      no significant gender differences. The corresponding treatment prevalence rates
      were 22.4% and 31.1%, respectively for the diagnostic subjects and 6.9% and 6.1%,
      respectively for the sub-diagnostic groups. The total treatment prevalence rate
      was 37.2% of the population (males 30.0%, females 44.1%). CONCLUSIONS: Our
      findings reveal that psychiatric disorders are quite common in the general
      population. When the spectra of mental disorders are considered, nearly three
      quarters of the general population will have manifested at least one of the
      mental disorders across their lifetime. LIMITATIONS: The data are based on a
      relatively small sample; a single age cohort, and the study was conducted in
      Zurich, Switzerland. These study features may diminish the generalisability of
      the findings.

PMID- 16001704
TI  - [Drug prescription in Italian Residential Facilities].
AB  - AIMS: To investigate in a representative national sample (N=2,962) of patients
      living in Residential Facilities (RFs) patterns of polypharmacy as well as
      related variables, association between diagnoses and therapeutic patterns, and
      the rate of adverse events. METHODS: Structured interviews focusing on each
      patient were conducted by trained research assistants with the manager and staff
      of each RF. Patients were rated with the HoNOS and the SOFAS, and comprehensive
      information about their sociodemographic and clinical status, and their
      pharmacological regimes were collected. RESULTS: Conventional antipsychotics and
      second-generation antipsychotics were prescribed to 65% and 43% of the sample,
      respectively. Benzodiazepines were prescribed to two-thirds of the sample, while
      antidepressants were the least-used class of psychotropics. Polypharmacy was
      common: on average, each treated patient was taking 2.7 drugs (+/- 1.1);
      antipsychotic polypharmacy was also common. Many prescriptions were loosely
      related to specific diagnoses. Antiparkinsonianian drugs were prescribed to
      approximately 1/4 of the sample. Mild or severe adverse events in the previous
      month were reported for 9.9% and 1.4% of the sample, respectively. About 15% of
      patients suffered from tardive dyskinesia. CONCLUSIONS: Psychotropic drug
      prescription patterns for severe patients living in RFs are only sometimes
      satisfactory and offer the opportunity of improvement. Specific actions are
      required to improve prescription patterns for severe patients in RFs.

PMID- 16001705
TI  - Eating disorders and their correlates in high school adolescents of Northern
      Italy.
AB  - OBJECTIVE: The study investigated eating disordered behaviours and life-habits
      correlated in a large sample of Northern Italian adolescents of both sexes.
      METHODS: The study had a cross-sectional design. 2595 students (2,146 responders;
      mean age 17.2 +/- 1.7 years) attending high schools in Savona (Italy) in April
      and May 2001 were sampled. To assess eating attitudes, the Inventory for the
      Screening of Eating Disorders (ISED) was self-administered. Inquiries regarding
      possible risk factors for eating disorders were also made: socio-economic status,
      body weight, smoking and alcohol drinking habits, illegal drugs use. RESULTS:
      Females scored significantly higher than males at ISED (13.4 +/- 7.7 vs. 7.6 +/-
      5.8). 28.5% of females had a total ISED score above the cut-off point (18/19).
      Unhealthy eating behaviours were strongly associated with higher BMI, body image
      disturbance and illegal drugs use in both sexes; age had significant role only in
      males. No significant association between disordered eating behaviours and socio
      economic status, smoking habit and alcohol consumption were found. CONCLUSIONS:
      Symptoms of eating disorders are quite spread in the Northern Italian female
      adolescents and associate with illegal drugs use. These data, with not negligible
      frequency of unhealthy eating behaviours and attitudes in males too, suggest that
      primary and secondary preventive interventions for teen-agers should be got
      ready.

PMID- 16001706
TI  - [Epidemiology of overweight and obesity among Italian early adolescents: relation
      with physical activity and sedentary behaviour].
AB  - AIMS: The prevalence of overweight and obesity and the role of possible related
      factors were analysed among Italian early adolescents. METHOD: 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). RESULTS: The overall prevalence is
      16.7% for overweight and 2.5% for obesity. Boys are more at risk than girls for
      the two phenomena. Moreover, age group, mother's education, area of residence,
      physical activity, and sedentary behaviour show a significant association with
      both outcomes. CONCLUSION: Findings of the present study are in agreement with
      similar studies carried out on early adolescents population, showing that
      prevalence in overweight and obesity decreases during this phase and is more
      diffused among boys than girls. The prevalence of both diseases is higher in the
      South and Islands. Sedentary behaviour and physical activity are substantive
      factors which preventive interventions could act on.

PMID- 16001707
TI  - [The role of the environmental factors on the development of adaptive skills in
      intellectual disabilities subjects].
AB  - AIMS: The aims of the study was to evaluate if environmental factors can
      influence the effectiveness of therapeutic intervention of subjects with
      intellectual disabilities. METHODS: 46 adolescents and adults with mental
      retardation, in semi-residential rehabilitative treatment, have been assessed
      over a 2-years period. The evolution of adaptive functioning over time has been
      assessed through the AAMD-ABS. The development of the adaptive skills at follow
      up has been correlated with socio-economic and cultural factors. RESULTS: Linear
      regression showed that age of both parents, mother's health status, lack of one
      parent, SES, and housing conditions, represent significant covariates to
      predicting evolution of the adaptive functioning; these factors independently
      influence effectiveness of the therapy from the kind of treatment. CONCLUSION:
      The results demonstrate that effectiveness of the therapy can be conditioned from
      ability to fulfil the needs of the families, through social and supporting
      programs.

PMID- 16001708
TI  - Monitoring the environment: taking a historical perspective.
AB  - This paper introduces the five papers that follow, all of which were originally
      presented at a workshop titled "Monitoring the Environment: Scales, Methods, and
      Systems in Historical Perspective." The workshop, sponsored by the Society for
      the History of Technology and the American Society for Environmental History,
      examined past efforts to develop tools, methods, and systems for measuring or
      monitoring some aspect of the physical environment. Four of the papers included
      here focus on various aspects of air quality monitoring; the fifth has to do with
      monitoring the earth from space. Despite differences in time period and approach,
      each article examines how specific tools and methods--and the motivations for
      developing those tools and methods--evolved. Among other things, these papers
      make clear that systems for monitoring various aspects of the physical
      environment are shaped by a variety of stakeholders and suggest that efforts to
      construct such systems should not be viewed as a purely technical task.

PMID- 16001709
TI  - The strange career of the Ringelmann smoke chart.
AB  - The Ringelmann smoke chart was used in the United States to assess smoke
      emissions in the early twentieth century. In fact, it may have been the most
      important method for measuring air pollution between the late 1800s and the
      environmental era. However, the popularity of the Ringelmann chart stood in stark
      contrast to its lack of precision, which smoke abatement experts recognized and
      discussed among themselves. However, the critique of the Ringelmann scale rarely
      left the circle of experts and never jeopardized its use. This article discusses
      the reasons for this striking phenomenon, pointing out that the Ringelmann chart
      had strong practical and symbolic advantages: it allowed smoke abatement to be
      conducted in a public and transparent way. With that, the history of the
      Ringelmann smoke chart is an instructive model for the social construction of
      measuring techniques.

PMID- 16001710
TI  - 1 to 100: creating an air quality index in Pittsburgh.
AB  - Air pollution indices and other environmental quality indicators have often been
      subjects of debate. This article presents a case study of the creation and
      criticism of an air pollution index in Pittsburgh, Pennsylvania. Long known for
      its industrial production and the resulting pollution, Pittsburgh was home to
      engineers, scientists, institutions and corporations that developed new air
      pollution monitoring technologies in the years after World War II. These newly
      automated instruments were used as a part of a computerized monitoring network
      built in the late 1960s by the Allegheny County Health Department. County
      engineers created a daily air pollution index to summarize the information from
      the network, leading to public debates over the intent, meaning, and
      representation of air quality data. This case study serves to illustrate the
      inherent complexity of creating accessible, understandable, and uniformly
      acceptable indices of environmental quality. It also emphasizes the importance of
      understanding the social and political context in which data is collected,
      organized, and interpreted.

PMID- 16001711
TI  - Characterizing and controlling industrial dust: a case study in small particle
      measurement.
AB  - Instrumentation used to measure characteristics of fine particles entrained in
      gas or suspended in aerosols provides information needed to develop valid
      regulations for emission sources and to support the design of control
      technologies. This case study offers a brief history of "micromeritics," a term
      used by early researchers to describe the science of small particles, and the
      related invention of laboratory instruments for characterizing very fine
      particles. The historical view provides insights into the role that Progressive
      Era government agencies played in advancing esoteric science and applying this
      knowledge to the regulation of workplace air pollution. Micromeritics
      instrumentation developed in conjunction with federal research now has many
      commercial applications worldwide, with characterizing airborne pollutants only a
      minor one. However, the continuing advances in the micromeritics field provide
      important laboratory measurement capabilities to environmental research
      organizations, such as the National Institute for Occupational Safety and Health
      (NIOSH).

PMID- 16001712
TI  - Learning to see the invisible: discovery and measurement of ozone.
AB  - Ozone is a key trace constituent of the atmosphere that is interesting for
      multiple reasons, including its ability to serve both as a screen against harmful
      solar radiation and as an aggressor against human health. However, methods for
      accurately detecting and measuring ozone were required before the behavior of
      ozone in the atmosphere and the effect of human activity on that behavior could
      be understood. This paper traces out the history of technologies and practices in
      ozone monitoring that have made this understanding possible, from nineteenth
      century chemical indicators to modern, laser-based detection technologies. Key
      insights include the importance of interactions between theorizing and
      observation in the process of scientific discovery, the importance of
      intercomparisons between different types of instruments, the way in which public
      policy concerns changed the pace and direction of ozone monitoring in the 1970s,
      and the importance of long-term environmental monitoring data to both improving
      our understanding of earth systems and protecting human health and the
      environment.

PMID- 16001713
TI  - The impact of landsat satellite monitoring on conservation biology.
AB  - Landsat 7's recent malfunctioning will result in significant gaps in long-term
      satellite monitoring of Earth, affecting not only the research of the Earth
      science community but also conservation users of these data. To determine whether
      or how important Landsat monitoring is for conservation and natural resource
      management, we reviewed the Landsat program's history with special emphasis on
      the development of user groups. We also conducted a bibliographic search to
      determine the extent to which conservation research has been based on Landsat
      data. Conservation biologists were not an early user group of Landsat data
      because a) biologists lacked technical capacity--computers and software--to
      analyze these data; b) Landsat's 1980s commercialization rendered images too
      costly for biologists' budgets; and c) the broad-scale disciplines of
      conservation biology and landscape ecology did not develop until the mid-to-late
      1980s. All these conditions had changed by the 1990s and Landsat imagery became
      an important tool for conservation biology. Satellite monitoring and Landsat
      continuity are mandated by the Land Remote Sensing Act of 1992. This legislation
      leaves open commercial options. However, past experiments with commercial
      operations were neither viable nor economical, and severely reduced the quality
      of monitoring, archiving and data access for academia and the public. Future
      satellite monitoring programs are essential for conservation and natural resource
      management, must provide continuity with Landsat, and should be government
      operated.

PMID- 16001714
TI  - Mexican Registry of Acute Coronary Syndromes.
AB  - OBJECTIVE: The registry intends to establish the clinical characteristics,
      identify therapeutic approaches and describe in-hospital outcome of patients with
      acute coronary syndromes in Mexico. METHODS AND RESULTS: RENASICA II is a
      prospective registry that included 8,098 patients with final diagnosis of acute
      coronary syndromes. Three thousand five hundred and forty three patients had
      unstable angina or non-ST elevation myocardial infarction (UA/NSTEMI) and 4,555
      ST elevation myocardial infarction. (STEMI) On admission typical chest pain was
      identified in 78% and 85% respectively. Non-ST elevation high risk group was
      identified in 36%. In STEMI group anterior myocardial infarction and Killip class
      I had a higher occurrence. The use of aspirin, unfractionated heparin, low
      molecular weight heparin, nitrates, beta blockers and ACE inhibitors for patients
      with UA/NSTEMI were 90%, 50%, 45%, 58%, 50% and 54% respectively, with
      corresponding rates of 88%, 54%, 44%, 66%, 51% and 64% for STEMI patients.
      Coronary angiography, angioplasty and coronary bypass surgery were performed in
      62%, 30% and 8% in UA/NSTEMI patients respectively with corresponding rates of
      44%, 27% and 4% for the STEMI group. Among patients with STEMI 37% were under
      fibrinolytic therapy and 15% received primary or facilitated angioplasty. Overall
      In-hospital mortality was 7%, 4% UA/NSTEMI and 10% STEMI 10%. CONCLUSION: The
      largest registry ACS in Latin-America provides important and reliable information
      on the complete spectrum, outcome, quality of care, and identifies areas for
      further improvement of the quality of our cardiovascular care. RENASICA II
      broadens our knowledge about how reperfusion and antithrombotic approaches modify
      the outcome and what needs to be improved in the real practice in Mexico.

PMID- 16001715
TI  - In vivo degradability of hydrogels prepared from different gelatins by various
      cross-linking methods.
AB  - This study is an investigation to evaluate the in vivo degradation of gelatin
      hydrogels in terms of their number of cross-links. Various hydrogels were
      prepared from acidic gelatin, extracted from bovine bone, porcine skin or fish
      scale, and basic gelatin, extracted from porcine skin, through four types of
      cross-linking methods, i.e., glutaraldehyde (GA) or dehydrothermal treatment and
      ultraviolet (UV) or electron beam irradiation. The water content of hydrogels and
      their number of cross-links, calculated from the tensile modulus of hydrogels,
      were evaluated as the measure of hydrogel cross-linking extent. Following
      subcutaneous implantation of 125I-labeled gelatin hydrogels into mice, the
      radioactivity remaining was measured at different time intervals to assess the in
      vivo degradability of hydrogels. Irrespective of the gelatin type and cross
      linking method, a good correlation was found between the in vivo degradability of
      hydrogels and their number of cross-links, which is different from the
      correlation to their water content. This finding indicates that the degradability
      of hydrogels is governed by their number of cross-links.

PMID- 16001716
TI  - Interaction of 1-dodecyl-azacycloheptan-2-one with mouse stratum corneum.
AB  - The interactions of 1-dodecyl-azacycloheptan-2-one (Azone), a penetration
      enhancer, with mouse skin were analyzed by fluorescence microscopy, solid-state
      13C-CP/MAS-NMR spectroscopy and Attenuated Total Reflectance Fourier-transform
      infrared (ATR-FT-IR) spectroscopy. Ferulic acid was employed as fluorescent probe
      to observe the delivery pathway in the stratum corneum (SC) after treatment with
      Azone. Results suggested that the interaction between Azone and the SC occurs in
      the lipid domains as well as the protein domains. FT-IR measurements show that
      treatment with Azone results in significant shifts toward larger wavenumbers at
      v(as)CH2 and v(s)CH2, indicating an increased gauche conformational isomer
      content of lipid CH2. Further, a decrease of (13C)T1 values and a shift of the SC
      protein amide-II band to a short wavenumber were found when the SC was pretreated
      with Azone. It is concluded that Azone can partially convert the SC protein from
      an alpha-helix conformation to a beta-sheet conformation and loosen the
      aggregating SC keratins at room temperature.

PMID- 16001717
TI  - Preparation of macroporous polymer scaffolds using calcined cancellous bone as a
      template.
AB  - A technique for preparing porous polymeric scaffolds using calcined cancellous
      bone as template has been developed. The scaffolds prepared by this method were
      morphologically similar to the structure of the demineralized bone matrix (DBM),
      i.e. scaffolds prepared by this novel method possessed high porosity,
      interconnected pores and uniform pore distribution. In addition, the mechanical
      properties of the scaffolds prepared by this novel method were significantly
      improved as compared to that of the scaffolds prepared by conventional solvent
      cast-particle leaching (SC-PL) method. The effects of concentration of the
      polymer solution on the structure, porosity and mechanical properties of the
      scaffolds were evaluated and the results showed that the mechanical properties of
      the scaffolds could be controlled by adjusting the concentration of the polymer
      solution. The advantages mentioned above suggest that this novel method might be
      a useful technique to prepare polymer scaffolds for tissue engineering.

PMID- 16001718
TI  - Effect of surfactant on the characteristics of biodegradable microcapsules.
AB  - The objective of this project was to evaluate the effect of several lipophilic
      surfactants on the characteristics of PLGA microcapsules. BSA was used as a model
      peptide. Seven different lipophilic surfactants were used and each of the
      surfactants was used at three different concentrations, 0.1, 0.5 and 1% (w/w),
      respectively. The microcapsules were prepared using the double emulsion solvent
      evaporation technique. The microcapsules were all spherical in shape with a
      smooth surface. The median size of the microcapsules varied between 4 and 49
      microm. The zeta potential of the microcapsules varied between -26 and -43 mV.
      The efficiency of encapsulation varied between 8 and 45%. Efficiency of
      encapsulation appears to be dependant on both the type and concentration of the
      surfactant. Cumulative percent of BSA released up to 35 days varied from 18 to
      78%. In conclusion, the physical characteristics of the microcapsules do not
      appear to be greatly affected by the type of surfactant. All of the samples
      appear to show polydispersity in their particle sizes. Particle charge depended
      on both the type and concentration of the surfactant. The overall dissolution of
      these microcapsules was very slow.

PMID- 16001719
TI  - Synthesis of diagnostic test kits for syphilis with polymeric particles.
AB  - This investigation aimed to derive alternative guidelines for syphilis. In the
      first step of this study monodisperse PGMA particles were synthesised by
      dispersion polymerization of the GMA monomer by using AIBN as initiator and PAA
      as stabilizator. A series of characterization experiments were done. In the
      second step of the study the characterized particles were used as microcarriers
      for the immobilization of the natural antigen for the purpose of diagnosing
      syphilis. The covalent binding method was used and GA was utilized as a spacer
      arm. The optimum immobilization conditions for the binding of natural antigen
      onto the particles were determined. In the third and the last step of the study
      the agglutination tests were realized with in vitro experiments by using both
      serum samples taken from syphilis patients and positive controls. After these
      experiments the kits chosen among the ones showing high performance were compared
      with the commercial RPR kit being used widely by reacting with serially diluted
      positive controls and patient serums. After this comparison the performances of
      the synthesized kits were found as satisfactory as the commercial kits.

PMID- 16001720
TI  - Quantitative chemical mapping of sodium acrylate- and N-vinylpyrrolidone-enhanced
      alginate microcapsules.
AB  - Alginate microcapsules enclosing recombinant cells secreting therapeutic products
      have been used successfully to treat several murine models of human diseases. The
      mechanical and chemical properties of these alginate capsules can be improved by
      the addition and in situ photo-polymerization of sodium acrylate and N
      vinylpyrrolidone in the alginate capsule. The purpose of this modification was to
      form additional covalent cross-links. In this work we have used scanning
      transmission X-ray microscopy (STXM) to probe the nature and location of the
      chemical modifications in the modified capsules by comparison with unmodified
      capsules. Analysis of X-ray image sequences and selected area spectra has been
      used to map the calcium gradient in capsules, to identify the presence of
      polyacrylate throughout the capsules and the localization of poly-N
      vinylpyrrolidone in the outer regions of the alginate capsules. The differences
      in the spatial distributions of these species have led to better understanding of
      the chemical modifications that provide a mechanically more stable capsule
      structure.

PMID- 16001721
TI  - Structural properties of biodegradable polyesters and rheological behaviour of
      their dispersions and films.
AB  - This paper focuses on the dependence of the rheological properties of PLA-PEG and
      PLGA dispersions and films on the polymer structural properties, in order to
      obtain useful information to predict and explain the performance of polyester
      films as drug-delivery systems. In this study, one PLA-PEG and three PLGA
      polymers of different molecular mass were synthesized and characterized by NMR,
      GPC, DSC and TGA-FT-IR. To characterize the viscoelastic behaviour of
      concentrated solutions in dichloromethane and of the films obtained by a solvent
      casting technique, oscillatory shear rheometry was used. The polymer dispersions
      showed a characteristic Newtonian viscous behaviour, but with different
      consistency index depending on the nature of the polymer. Freshly prepared, PLGA
      and PLA-PEG films had elastic modulus (G') greater than viscous modulus (G"). The
      decrease in both moduli caused by an increase in temperature from 25 to 37
      degrees C was especially marked for the polymers with T(g) below or around 25
      degrees C (PLGA 27 kDa and PLA-PEG 27 kDa). After being immersed in pH 7.4
      aqueous solution for one week, PLGA films showed a significant increase in both
      G' and G", due to the promotion of polymer-polymer interactions in a non-solvent
      medium. In contrast, the PLA-PEG film became softer and more hydrated, due to the
      amphiphilic character of the polymer. The water taken up by the film acted as a
      plasticizer and induced the softening of the system. These results suggest that
      the presence of PEG chains exerts a strong influence on the mechanical properties
      of polyesters films and, possibly, the performance as coating or matrices of drug
      delivery systems.

PMID- 16001722
TI  - Degradation of P(3HB) and P(3HB-co-3HV) in biological media.
AB  - The biodegradability of oriented fibers made of polyhydroxybutyrate (P(3HB)) and
      its co-polymer with beta-hydroxyvalerate (P(3HB-co-3HV)) was investigated in
      buffer solutions and in biological media in vitro and in vivo. The fibers of both
      polymer types demonstrated resistance to hydrolytic degradation in buffer
      solutions at 38 degrees C and pH from 4.5 to 7.0 (for up to 180 days). It has
      been found that the biodegradation of the fibers in vitro in blood and serum and
      in vivo is accompanied by weight losses and minor changes in the microstructure
      with no significant losses in the tensile strength over a long time (up to 180
      days). The biodegradation rate of the less crystalline co-polymer P(3HB-co-3HV)
      fibers was 1.4-2.0-times higher than that of the homopolymer P(3HB). It has also
      been shown that the degradation of the fibers in vivo is influenced both by
      tissue fluid enzymes and cells (macrophages and foreign-body giant cells). The
      fibers were eroded on the surface only with no gross defects and no dramatic
      effects on their mechanical performance.

PMID- 16001723
TI  - Nitric oxide-generating hydrogels inhibit neointima formation.
AB  - This study evaluated the effects of localized delivery of nitric oxide (NO) from
      hydrogels covalently modified with S-nitrosocysteine (Cys-NO) on neoinitma
      formation, a key component of restenosis, in a rat balloon-injury model. Soluble
      Cys-NO was used in preliminary studies to identify dosage ranges that were able
      to simultaneously inhibit smooth muscle cell proliferation, enhance endothelial
      cell proliferation, and reduce platelet adhesion. Photo-cross-linked PEG-based
      hydrogels were formed with covalently immobilized Cys-NO. These materials release
      NO for approximately 24 h and can be applied to tissues and photo-cross-linked in
      situ to form local drug-delivery systems. Localized delivery of NO from hydrogels
      containing Cys-NO inhibited neointima formation in a rat balloon-injury model by
      approximately 75% at 14 days.

PMID- 16001724
TI  - Immobilized metal affinity beads for ferritin adsorption.
AB  - A new metal-chelate adsorbent utilizing N-methacryloyl-(L)-cysteine methyl ester
      (MAC) was prepared as a metal-chelating ligand. MAC was synthesized by using
      methacryloyl chloride and L-cysteine methyl ester dihydrochloride. Spherical
      beads with an average diameter of 150-200 microm were produced by suspension
      polymerization of 2-hydroxyethyl methacrylate (HEMA) and MAC carried out in an
      aqueous dispersion medium. Then, Fe(3+) ions were chelated directly on the beads.
      Properties such as specific surface area, specific pore volume and ligand
      occupation were determined. The specific surface area of the beads was found to
      be 18.9 m2/g. The total pore volume was 2.8 ml/g and represented a porosity over
      52%. The average pore size of the poly(HEMA-MAC) beads was 620 nm. Fe(3+)
      chelated beads were used in the adsorption of ferritin from aqueous solutions.
      Ferritin adsorption increased with increasing ferritin concentration. The maximum
      ferritin adsorption capacity of the Fe(3+)-chelated poly(HEMA-MAC) beads (Fe(3+)
      loading 0.81 mmol/g) was found to be 3.7 mg/g at pH 4.0 in acetate buffer. The
      non-specific ferritin adsorption on the poly(HEMA-MAC) beads were 0.4 mg/g.
      Adsorption behavior of ferritin could be modelled using both the Langmuir and
      Freundlich isotherms. Adsorption capacity decreased with increasing ionic
      strength of the binding buffer. Ferritin molecules could be adsorbed and desorbed
      five times with these adsorbents without noticeable loss in their ferritin
      adsorption capacity.

PMID- 16001725
TI  - [Surgical procedure for Warthin's tumor in the parotid gland].
AB  - Warthin's tumor is benign and exclusively involves the parotid gland but may,
      however, often show multifocal and/or bilateral growth. The aim of this study was
      to evaluate the surgical procedure for removal of this tumor. Sixty patients with
      Warthin's tumor in the parotid gland who presented at the Kansai Medical
      University Hospital from 1990 to 1999 were the subjects of the present study. The
      surgical procedures were as follows. We performed enucleation for tumors in the
      deep lobe. Tumors in the superficial lobe were resected with partial
      parotidectomy, and an enucleative procedure was also performed at the bottom of
      the tumor where the tumor capsule directly touched the facial nerve. No
      recurrence was observed in all sixty cases including cases of rupture of the
      capsule before or during surgery. Therefore, we recommend that enucleation is a
      useful choice as a surgical procedure for the removal of Warthin's tumor after
      accurate detection of the tumors using MRI. The overall incidences of temporary
      and permanent facial nerve palsy were 19.7% and 0%, respectively. The incidence
      of palsy increased after surgery for multiple tumors or deep lobe tumors. These
      findings indicate that more careful consideration for preservation of the facial
      nerve should be given in such cases and that simultaneous surgery for such tumors
      in the bilateral parotid glands should be avoided to prevent bilateral facial
      nerve palsy.

PMID- 16001726
TI  - [Managing small pulmonary nodules in head and neck malignant tumors].
AB  - The recent increase in the use of helical CT has produced a higher detection rate
      of small pulmonary nodules than in conventional CT application, and has presented
      a serious problem in their treatment. We carried out a retrospective study to
      identify a clinical standard in the management of those nodules in head and neck
      malignant tumors. The subjects were 108 in-and out patients (87 men and 21 women)
      with head and neck malignant tumors who received radiation therapy in our
      university hospital between 2003 and 2004 (ages ranging from 25 to 93 years;
      mean, 66 years). Helical CT of the chest was applied to 92 patients of the 108
      (85%). We determined small pulmonary nodules as round nodules 5 mm or more and
      less than 1 cm in diameter, and observed them in 14 of the 92 (15%). Firstly, we
      compared nodule growth by dividing the patients into 2 groups. The nodules grew
      in 2 of 7 patients of Group I, where chemotherapy was not done or where
      chemotherapy was not effective on the primary tumor, and in 3 of 7 patients of
      Group II, where chemotherapy was effective on the primary tumor. Secondly,
      disregarding the effects of chemotherapy, we analyzed nodule growth: the nodules
      grew in 5 of the 14 patients (36%). Those small pulmonary nodules were all
      pulmonary metastases. When small pulmonary nodules are detected by helical CT,
      accompanying malignant tumors of the head and neck, and bearing in mind the
      probability of their growth of at least 36%, we should therefore follow them up
      carefully.

PMID- 16001727
TI  - [Intraarterial concomitant chemoradiation for tongue cancer: analysis of 20
      patients].
AB  - Subjects were 20 patients with tongue cancer treated between April 1996 and
      December 2002 with intraarterial infusion of cisplatin (60-120 mg/m2) (and
      docetaxel 10-30 mg/m2) and intravenous infusion of sodium thiosulfate followed by
      5-fluorouracil (5-FU) (800-1000 mg/m2) for 3 to 5 days. All patients underwent
      radiation (50-80 Gy). Ten had stage II, 4 stage III, and 6 stage IV A disease.
      Complete response at the primary site was achieved in 50% for T2, 67% for T3, and
      0% for T4 lesions in those undergoing IA cisplatin followed by systemic 5-FU with
      concurrent radiation. Complete response at the primary site was achieved in all
      patients given IA cisplatin and docetaxel followed by systemic 5-FU with
      concurrent radiation. Disease-specific survival was 75% and overall survival 69%
      at 5 years. Side effects of treatment were tolerable, except for grade three
      radiomucositis in 70% of patients and grade three bone marrow depression in one
      treated with weekly IA chemotherapy.

PMID- 16001728
TI  - [Congenital anterior cervical fistula originating from the Wharton duct].
AB  - A 14-year-old boy presented with a spontaneous anterior cervical fistula, which
      exuded a saliva-like fluid during eating. Cervical examination revealed a hole 7
      mm posterior to the hyoid bone, 5mm left of the median. Magnetic resonance
      imaging showed a low-intensity spindly mass with high-intensity margins. The mass
      was connected to the left submandibular gland. Contrast radiography of the
      fistula using Gastrografin demonstrated an ascending fistula that extended to the
      submandibular area. Intraoperatively, the fistula was shown to have ascended
      superficial to the level of the anterior cervical muscles, and it formed a cyst
      anterior to the hyoid bone. It then continued to the left submandibular gland.
      The fistula and submandibular gland were removed together. Wharton's duct was not
      found, and the orifice of the duct was unclear. Pathological examination of the
      fistula showed the lining epithelium at the side of the submandibular gland to be
      composed of columnar epithelial cells with stratified squamous cells at the
      epidermal side. Several acinar systems were found along the orifice of the
      fistula. There have been no previous reports of the Wharton duct running from the
      submandibular gland to the anterior cervical skin.

PMID- 16001729
TI  - [Case of cystic metastasis of lingual tonsil carcinoma diagnosed first as a
      branchiogenic cyst].
AB  - We report a case of lingual tonsil carcinoma diagnosed first as a branchiogenic
      cyst. Histopathological findings showed the possibility of a malignant tumor
      because there was proliferation of the papillary epithelium of the cyst wall.
      Blind biopsy of the lingual and palatine tonsil was done and the histological
      findings revealed a cystic metastatic lymph node from a squamous cell carcinoma
      (SCC) of the lingual tonsil. The diagnosis of the primary unknown cystic
      metastatic cervieal SCC requires a thorough examination of the palatine or
      lingual tonsil when there is no evidence of any vestigial remnant of
      branchiogenic organ.

PMID- 16001730
TI  - All-ceramic fixed partial dentures. Studies on aluminum oxide- and zirconium
      dioxide-based ceramic systems.
AB  - BACKGROUND: The development of refined, tougher, and stronger ceramic core
      materials in recent years has led to the wider use of new, strong all-ceramic
      systems based on oxide ceramics. Results from in-vitro studies investigating the
      use of oxide ceramics in shorter all-ceramic fixed partial dentures (FPDs) have
      been positive, but clinical studies and additional in-vitro studies are needed to
      confirm the advisability of such procedures. AIMS: One aim of this thesis was to
      investigate whether alumina-based and zirconia-based material systems are
      adequate for use in shorter (< or = five-unit) FPDs and to evaluate the clinical
      results. Additional aims were to investigate how to achieve optimal fracture
      strength in an all-ceramic FPD by varying the try-in procedure, the cervical
      shape of the abutments, and the support of the FPD (abutment teeth or dental
      implants). The final aim was to compare the strength of a zirconia material
      system with that of an alumina equivalent with known long-term clinical
      performance. MATERIALS AND METHODS: Two clinical studies investigating one
      alumina-based and one zirconia-based material system were performed. Twenty
      posterior, three-unit FPDs (glass-infiltrated alumina) were followed for 5 years
      and 20 three-five-unit FPDs (HIP zirconia) for 2 years. Long-term follow-ups were
      made after 11 +/-1 (glass-infiltrated alumina) and 3 years (HIP zirconia). In
      three in-vitro studies, the following variables were investigated: (1a) the
      flexural strength of porcelain specimens depending on whether they were exposed
      to saliva before the glaze firing (n=20) or first after the glaze firing (n=20),
      (1b) the fracture strength of three-unit all-ceramic FPDs (glass-infiltrated
      alumina) supported by abutments prepared with cervical shoulder preparations
      (n=9) and abutments with cervical chamfer preparations (n=9), (2) the fracture
      strength of crowns (n=30) made of a zirconia material system (densely sintered
      zirconia) and of crowns (n=30) of an alumina material system (densely sintered
      alumina) that had undergone three different pre-treatment modalities (water
      storage only; water storage and cyclic pre-loading; water storage, cyclic pre
      loading, and thermocycling), (3) the fracture strength of all-ceramic FPDs
      (densely sintered alumina) supported by simulated teeth (n=12) or by dental
      implants (n=12). RESULTS: The success rate of the clinical alumina study was 90%
      after 5 years. Six (+/-1) years later (after a total of 11 +/-1 years), the
      success/survival rate was 65%. In the second clinical study, the success rates of
      the 2- and 3-year follow-ups were 100%. In the three in-vitro studies, the
      following results were found: (1a) the mean flexural strength of the specimens in
      the group that was exposed to saliva first after glazing was significantly higher
      (P < 0.001) than that of the specimens in the group that was exposed to saliva
      before glazing, (1b) the FPDs luted on shoulder preparations resisted higher
      loads than the FPDs luted on chamfer preparations (P = 0.051), 2) total fractures
      were more frequent in the alumina than in the zirconia group (P < 0.001), 3) FPDs
      loaded on implants resisted higher loads (mean = 604 N, SD=184 N ) than FPDs
      loaded on abutment teeth (mean= 378 N, SD=152 N, P = 0.003). CONCLUSIONS: This
      thesis justifies the use of shorter alumina- (< or = three-unit) and zirconia
      based (< or = five-unit) FPDs as the clinical results are acceptable. The
      clinical performance of alumina is, however, not as good as that of comparable
      high-gold alloy based porcelain-fused-to-metal FPDs concerning fracture
      resistance. Within the limitations of the in-vitro studies: Saliva exposure of
      porcelain before glaze firing should be avoided to optimize the strength of the
      porcelain. Shoulder preparations can be beneficial for the strength of all
      ceramic FPDs compared to chamfer preparations, as can support by dental implants
      compared to abutment teeth. The fracture mode of alumina crowns (total fractures)
      differs from that of zirconia crowns (veneer fractures), suggesting that the
      zirconia core is stronger than the alumina core.

PMID- 16001731
TI  - Renova Internal Hex Implant System: surgical and restorative versatility.

PMID- 16001732
TI  - The state of our specialty.

PMID- 16001733
TI  - Clinical considerations for densely sintered alumina and zirconia restorations:
      Part 1.
AB  - Densely sintered alumina- and zirconia-based restorations were introduced to
      dentistry in the early 1990s and became a popular treatment modality, especially
      in situations requiring complete-coverage restorations. The use of industrial
      technologies for the fabrication of the restoration, simple clinical management,
      and pleasing esthetic outcome have made these restorations an attractive
      treatment alternative. This article reviews the nature of the materials used and
      the technologies involved and provides indications for clinical case selection
      and tooth preparation.

PMID- 16001734
TI  - The CO2 laser for excisional biopsies of oral lesions: a case series study.
AB  - During a period of 12 months, 139 patients with 164 intraoral pathologic lesions
      were treated with a CO2 laser. Intra- and postoperative complications and the
      method of pain control during and after surgery were recorded. The diagnostic
      evaluability of the 133 soft tissue biopsy specimens sent for histopathologic
      analysis was examined, and the clinical and histopathologic diagnoses were
      compared. Nine intra- and six postoperative complications occurred. Pain control
      during CO2 laser surgery could be performed with a topical anesthetic in almost
      one third of the lesions; in the other 111 lesions, a local anesthetic had to be
      applied. For pain relief after the operation, 101 patients (72.7%) used only an
      adhesive wound paste, without any additional oral analgesic. The thermal damage
      from the CO2 laser on the borders of the biopsy specimens never interfered with
      the pathologist's establishment of a firm diagnosis. The CO2 laser is an
      appropriate instrument for excisional biopsies of oral soft tissue lesions. Intra
      and postoperative complications were minimal, pain relief during and after
      surgery could be achieved in many cases through topical anesthetics, and
      incisional or excisional biospsies caused no diagnostic problems because of
      collateral thermal damage of the specimen from the laser.

PMID- 16001735
TI  - Histologic evaluation of mineralized and demineralized freeze-dried bone
      allograft for ridge and sinus augmentations.
AB  - The objective of this study was to quantify new bone formation from biopsies of
      demineralized freeze-dried bone allograft (DFDBA) and freeze-dried bone allograft
      (FDBA) following ridge and sinus augmentations. Ninety-three patients who
      received maxillary sinus or ridge augmentation grafts agreed to core biopsies of
      their grafts when the implants were placed. Samples ranged from 6 to 36 months
      postgrafting. These samples were sectioned, stained, and examined
      histomorphometrically Seventy-two FDBA and 21 DFDBA samples were examined, and
      the mean percentages of new bone formed were 41.89% and 41.74%, respectively.
      There was no statistical difference, irrespective of graft site.

PMID- 16001736
TI  - Esthetic restoration with orthodontic traction and single-tooth implant: case
      report.
AB  - This case report describes the use of orthodontic traction to recover soft tissue
      lost around a maxillary right central incisor with major external root resorption
      associated with severe gingival recession. Traction of the residual root for 1
      month produced a gingival appearance in harmony with the adjacent teeth. After
      the placement of an implant, a correct emergence profile was obtained, giving an
      optimal esthetic outcome. After a 3-year follow-up, complete regeneration of soft
      tissue persisted around the implant-supported crown.

PMID- 16001737
TI  - Relationship between position of probe tip and periodontal tissues after
      periodontal surgery in dogs.
AB  - The aim of this study was to investigate postsurgical periodontal probe
      penetration by using clinical information and histometric data. Thirty-eight
      three-walled defects were created in four dogs, then maintained for 3 months.
      Subsequently, 26 defects were subjected to periodontal surgery (surgical group),
      while 12 defects served as controls. The dogs were sacrificed at 4, 8, 12, and 16
      weeks. Immediately before sacrifice, endodontic silver points were placed in the
      gingival crevices as substitutes for periodontal probes and fixed on the teeth.
      Following block sections, histologic and histomorphometric evaluations were
      undertaken: location of the probe tip in relation to the apical termination of
      the junctional epithelium, length of new junctional epithelium in relation to the
      apical junctional epithelium, and mean length of connective tissue adhesion in
      relation to the apical junctional epithelium. Probe tips were located -1.37 +/-
      1.73 mm and -0.20 +/- 0.15 mm apical to the apical junctional epithelium for the
      surgical and control groups, respectively, at 4 weeks, while the probe tip was
      located 0.58 +/- 0.31 mm and 0.40 +/- 0.20 mm coronal to the apical junctional
      epithelium, respectively, at 16 weeks. Length of new junctional epithelium in
      relation to apical junctional epithelium was significantly less for the surgical
      than the control group at 4 weeks (0.73 +/- 0.60 mm vs 1.19 +/- 0.02 mm) and 8
      weeks (1.77 +/- 0.52 mm vs 2.15 +/- 0.00 mm). There were no significant
      differences between the groups in regard to connective tissue relationship to the
      apical junctional epithelium. Periodontal probing is not recommended for at least
      2 months after surgical procedures; before this stage, probing forces may damage
      the soft tissue-tooth interrelationship.

PMID- 16001738
TI  - A technique for augmenting the palatal connective tissue donor site: clinical
      case report and histologic evaluation.
AB  - This case report describes a simple method for augmenting tissue at prospective
      palatal connective tissue donor sites. The patient was referred for treatment of
      facial marginal tissue recession on the maxillary left canine. Clinical
      examination indicated that the palatal mucosa was thin and did not provide an
      adequate volume of soft tissue for donor harvesting, precluding the use of a
      palatal connective tissue graft for treatment of the recession defect. Sterile
      lyophilized bovine collagen sponge was therefore surgically inserted between a
      full-thickness palatal flap and bone at the prospective donor site. Eight weeks
      postoperative, the augmented palatal donor area showed a significant clinical
      increase in thickness and volume and served as a connective tissue donor source
      in the treatment of the facial marginal tissue recession. Histologic analysis of
      the donor tissue demonstrated normal structure, fibrous connective tissue, and
      abundant collagen. Clinical examination 6 months following surgery showed
      complete root coverage, with tissue texture, volume, and color similar to those
      of the adjacent soft tissue. Healing of the donor site was uneventful. This case
      report demonstrates that sterile lyophilized collagen sponge material may be used
      to augment palatal donor connective tissue and can subsequently be used as a
      donor source for soft tissue grafting.

PMID- 16001739
TI  - Attachment of periodontal ligament cells onto various antibiotics-loaded GTR
      membranes.
AB  - This study compared the natures of various guided tissue regeneration (GTR)
      membranes impregnated with amoxicillin or tetracycline. Whether the antibiotics
      loaded membranes enhance the attachment of the periodontal ligament cells in the
      presence of oral pathogens was further analyzed. S mutans and A
      actinomycetemcomitans diminished the attachment of periodontal ligament cells
      onto the membranes as evaluated by SEM analysis. These bacterial effects on
      cellular attachment could be reversed using the antibiotics-loaded membranes. The
      information obtained in this study is valuable for the future application of
      antibiotics-loaded membranes during GTR therapy.

PMID- 16001740
TI  - Effect of topical fluorides and citric acid on heat-pressed all-ceramic material.
AB  - The effects of citric acid and acidulated phosphate fluoride on the surface
      roughness of autoglazed and overglazed all-ceramic IPS Empress materials were
      analyzed. Atomic force microscopy was used to measure the roughness. Citric acid
      solution (2.00%) was applied for 8 hours, simulating 2 years of exposure.
      Acidulated phosphate fluoride gel (1.23%) was applied for 32 minutes, simulating
      2 years of fluoride therapy. Acidulated phosphate fluoride caused a significant
      roughening effect on both autoglazed and overglazed specimens.

PMID- 16001741
TI  - Two patterns of histologic healing in an intrabony defect following treatment
      with enamel matrix derivative: a human case report.
AB  - Human histologic evidence of periodontal regeneration following treatment of
      intrabony defects with enamel matrix derivative has yielded inconsistent results
      in recent case reports. A 46-year-old woman presenting one deep intrabony defect
      at the distal root of a mandibular first molar scheduled for extraction was
      selected for enamel matrix derivative therapy. During surgery, a notch was placed
      at the most apical level of calculus on the experimental root. Nine months
      postsurgery, a block section including the distal root and surrounding
      periodontal tissues was obtained and processed in a mesiodistal plane. Histologic
      analysis demonstrated two different patterns of healing along the proximal and
      furcal surfaces. Regeneration with new cellular cementum, bone, and periodontal
      ligament with functional fiber orientation was observed on the distal aspect of
      the root, whereas the furcal surface healed through ankylosis. This report
      underlines the biologic variability in wound healing following enamel matrix
      derivative therapy in periodontal intrabony defects and within the same defect.
      Host-specific intrinsic and/or extrinsic factors accounting for this variability
      remain to be investigated.

PMID- 16001742
TI  - [Reviewing the past and looking to the future].
AB  - The first issue of "Investigacion Clinica" was published in July, 1960; by the
      initiative of Dr. Americo Negrette. The journal had a small format (1/16) and was
      very sober in its presentation. It consisted of about 45 pages, with four
      articles, that were mainly the product of conferences and seminars. As time went
      by, 45 years of existence, our journal has evolved following the continuous
      changes on international regulations; such as the 1/8 format, the impression on
      acid-free paper and its bibliography in compliance with the Vancouver rules.
      Currently, Investigaci6n Clinica appears in the best international biomedical
      indexes and publishes eight original articles on average, in about 100 pages per
      number. It gets to 106 libraries and health centers in Venezuela and 102 abroad.
      International peer-review of research articles represents 50% of the current
      scientific reviews solicited. It is opportune to thank all of those that have
      collaborated, in such disinterested way, with the journal over the years, and to
      extend our gratitude to the Editorial and Advisory Boards, the financial
      supporters, the publishing companies that have worked in its final printing and,
      of course, to all the researchers that have confided in the responsibility,
      seriousness and punctuality of Investigaci6n Clinica.

PMID- 16001743
TI  - [Nutritional characterization by anthropometrics of institutionalized and non
      institutionalized elderly Venezuelan].
AB  - In order to evaluate nutritional status by anthropometry, a group of elderly (60
      to 83 years old) was studied: 63 institutionalized and 37 non-institutionalized
      elderly from Valencia city, Venezuela. Weight, height, triceps skinfold and mid
      arm circumference were measured and the body mass index (weight/height2) was
      calculated. The average age for the institutionalized group was 77.3 +/- 7.5
      years old and 69.5 +/- 7.6 years old for the free-living elderly group.
      Tricipital skinfold (TSF) and mid-arm circumference (MAC) means were within the
      normal reference range for both groups, without significant differences by sex.
      Body mass index (BMI) was higher in the institutionalized group. Lower BMI and
      MAC were found in older elderly (> or =80 y). According to the nutritional
      classification by BMI, 16% of nutritional deficit, 45% of normal status and 39.7%
      with of excess weight were found in institutionalized elderly; while in free
      living elderly, prevalences were 8%, 62% and 29.7% respectively. Even though
      normal nutritional status was highly prevalent, institutionalized elderly showed
      higher prevalences of nutritional alterations (underweight and overweight).

PMID- 16001744
TI  - [Iron stores status at early pregnancy].
AB  - Iron deficiency is the most common cause of nutritional anemia. During pregnancy
      there is a high risk of developing it, due to the increase of iron requirements
      for fetal and maternal tissues growth. The objective of this study was to
      determine the iron nutritional status in early pregnancy and to determine its
      relationship with the dietary intake. The study applied a cross-sectional and
      descriptive design in 419 pregnant women (13-41 y) from Valencia, Carabobo,
      Venezuela. Serum ferritin was determined by enzimoinmunoassay and hemoglobin by a
      semi-automated method. Dietary iron intake was assessed through two non
      consecutive 24 hours recalls. Statistical analysis included basic descriptives,
      Fisher exact test, Chi-square, and Mann-Whitney tests; with a statistical
      significance of p < 0.05. The iron deficiency and anemia prevalence were 16.2%
      and 14.4%, respectively; corresponding 36.6% to ferropenic anemia. 10.4%, 29.0%
      and 24.2% of the women had deficient intake for iron, vitamin C and A,
      respectively. There were no significant differences by age. A nutritional risk
      was observed regarding the iron status, demonstrated by the percentage of
      ferropenic anemia and because the main dietary contribution came from non-heme
      iron, which has low bioavailability. Additionally, there was an important
      percentage of inadequate vitamin C and A intakes; hence, their contribution to
      iron absorption was limited.

PMID- 16001745
TI  - [The goat: approach to an animal model in human chromomycosis].
AB  - In Falcon State, Venezuela, human chromomycosis is mainly caused by a dimorphic
      fungus, Cladophialophora carrionii. Xerophytes plants are common in the State and
      goat breeding in an extensive system as the main way of living. There are not
      published reports of chromomycosis in goats, despite the fact of their permanent
      exposition to fungus by accidental inoculation with infected spines. To evaluate
      parasitic transformation to sclerotic cells, length of fungus-surviving period
      and histopathological lesions, goats of five months of age were inoculated with 1
      x 10(6) cells of C. carrionii by subcutaneous route in the neck and biopsies at
      10, 19, 30 and 60 days from inoculated places were performed. Tissues were
      analyzed by (a) direct test with KOH 10%; (b) inoculation in Saboraud dextrose
      culture and (c) histopathological techniques. Hyphae and sclerotic cells were
      observed on tissues treated with KOH 10%; growing of fungus was detected in
      specific medium up to four weeks post-inoculation. Tissue pathology showed
      necrotic foci, mixed polymorphonuclear infiltrate, predominance of mononuclear
      cells, lymphocytes, plasmocytes, cosinophils and giant cells, hyphae and
      sclerotic cells in each one of samples. C. carrionii caused cellular reactions in
      goats as those seen in humans at the first stages of infection; however, animals
      did not develop the typical macroscopic lesions of the human disease.

PMID- 16001746
TI  - [Anthropometric characterization of an institutionalized elderly population from
      Caracas, Venezuela].
AB  - Most of the anthropometric standards are derived from adult populations but not
      from older subjects, so their use to evaluate the nutritional status in the
      elderly may not be the most appropriate. In this sense, the anthropometric
      characteristics and their relationship to sex and age in a cross-sectional sample
      of 809 Venezuelan subjects (370 males and 439 females), aged 60 to 102 years old,
      randomly selected from a elderly institution-alised population were studied. The
      results indicate that anthropometric variables show different degrees and signs
      of sexual dimorphism. Males presented higher stature, weight, waist and calf
      circumferences and higher bone diameters, while females have higher hip and thigh
      perimeters, and bigger trunk and extremities skinfolds. Independently of the
      changes observed in these variables with age, the difference spread between the
      sexes tends to stay and even to increase with age in the height and weight, in
      hip perimeter and in thigh and calf skinfolds; while, on the contrary, they
      attenuate in waist perimeter and in triceps, subescapular and suprailiac
      skinfolds. Males and females appear to be more similar for these variables in the
      advanced ages. In general, these results could be used as reference elements for
      similar researches in Venezuela, due to the low number of studies developed in
      the country in older populations

PMID- 16001747
TI  - [Relation of socioeconomic levels and life style to fibrinogen and von Willebrand
      factor in healthy Venezuelans and those with ischemic cardiopathy].
AB  - Previous studies in Europe, U.S.A and Japan have revealed an inverse relationship
      between socioeconomic levels and fibrinogen concentration. Similar results have
      been reported in a smaller number of studies for concentrations of von Willebrand
      factor. In this opportunity we present results on the relationship between
      smoking, drinking, physical activity, age and socioeconomic level on fibrinogen
      and von Willebrand factor concentrations in a Venezuelan sample. The control
      population consisted of 978 men and 968 women. Patients with coronary heart
      disease were 172 males and 78 females. The presence of one or more of the
      following conditions: smoking or less than 5 years of having quit, non drinkers
      or drinking in excess, and a reduced physical activity, was considered a health
      related risk factor for high levels of these two haemostatic variables. Our
      results indicate that in Controls, the socioeconomic level had a significant
      effect on fibrinogen and von Willebrand factor levels, only in women: those of
      lower socioeconomic levels had the highest concentrations. This difference was
      maintained when age was taken into account. Health related behaviors had no
      significant effect on either variable. In patients, age had no effect on either
      variable. The health behavior risk factor had a significant effect only on
      fibrinogen of male patients, and socioeconomic level had a significant effect
      only on the fibrinogen of female patients. More studies in Venezuela are
      recommended, in order to increase our knowledge on the relationship between
      socioeconomic levels, haemostatic markers and the occurrence of coronary heart
      disease.

PMID- 16001748
TI  - [Hepatic alterations in patients with dengue].
AB  - Clinical features of Dengue are very variable due to multiple alterations induced
      by the virus in the organism. Increased levels of transaminases similar to those
      produced by the Hepatitis virus have been reported in patients with Dengue from
      hiperendemic zones in Asia. The objectives of this study were to determine
      alterations in the liver tests in patients with Dengue and to relate them to the
      disease, clinically and serologically. Clinical history, hemathological tests
      serum transaminases (ALT y AST) and bilirubin assays were performed in 62
      patients with clinical and serological diagnosis of Dengue. According to clinical
      features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of
      Dengue reffered abdominal pain and 2 patients with DHF had ictericia and
      hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms
      of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x
      mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase
      values five fold higher than the normal values (p < 0.005) were observed in 36.8%
      and 74.4% of patients with CD and DHF respectively; AST was predominant in both
      groups. Our results suggest liver damage during the course of Dengue. A
      differential diagnosis has to be done between the hepatic involvement of Dengue
      cases and others viral diseases with hepatic disfunctions.

PMID- 16001749
TI  - [Comparative study of the effect of intravaginal misoprostol at 50 and 100
      micrograms in cervical ripening and labor induction].
AB  - The objective of this work was to compare the efficacy of 50 and 100 microg of
      misoprostol administered intravaginally for cervical ripening and labor
      induction. Ninety-five patients were randomly assigned to receive 50 microg
      (n=48) or 100 microg (n=47) of misoprostol. The primary measures in this study
      were cesarean section rate, time from induction to delivery, need for oxytocin
      use, rate of uterine hyperstimulation and tachysystoles, proportion of fetal
      distress and neonatal Apgar score. The interval from first dose of prostaglandin
      to delivery was significantly shorter in the 100 ,g-group (p < 0.05). The use of
      oxytocin augmentation was significantly higher in the 50 microg-group (64.6% vs.
      31.9%). There were 9 cases (18.8%) of tachysystole in the 50-microg group and 12
      cases (25.5%) in the 100 microg-group (p NS). The cesarean section rate was
      double in the 100 microg-group and the difference was statically significant (p <
      0.05). There was no report of uterine rupture. It can be concluded that 50 microg
      of misoprostol applied in the posterior vaginal fornix every 4 hours is an
      effective dosage for labor induction and has less adverse effects and
      complications than the 100 microg dose.

PMID- 16001751
TI  - Feels good and it works.

PMID- 16001750
TI  - [Plasma homocysteine concentration and its relationship with the development of
      preeclampsia. Effect of prenatal administration of folic acid].
AB  - The increase of plasmatic homocysteine (Hc) in pregnant women, who later develop
      preeclampsia/eclampsia, the cause of this increment and its pathogenic role in
      toxemia of pregnancy, are still controversial. The objectives of the present
      research were to determine the plasmatic He concentrations during the first and
      second trimesters of pregnancy and the effect of folic acid administration on
      these values, and in the prevention of preeclampsia. Ninety six pregnant women of
      low economic background were studied on the first prenatal consultation: 27 women
      in the first trimester of pregnancy and 59 in the second. After 8 hours of
      fasting, venous blood was extracted and each patient was provided with 1 mg folic
      acid tablets and instructed to ingest one tablet daily, and to come back to the
      laboratory after three months. Plasma homocysteine and serum folic acid were
      determined for each patient before and after the folic acid treatment, by using
      the IMX system (Abbott Lab) and radioimmunoassay, respectively. Basal
      homocysteine concentrations were 4.0 +/- 2.1 micromol/L and 4.8 +/- 2.1
      micromol/L in the first and second trimesters respectively, with no significant
      modifications after three months of folic acid. Although the degree of desertion
      from the study was high, it was possible to determine the evolution of 65
      pregnancies. Ten of them developed preeclampsia (15.4%). No significant
      differences were found in Hc concentrations, or the frequency of
      hyperhomocysteinemia in the different stages of pregnancy, between women with
      normal gestation and those who developed preeclampsia. The small sample size of
      these groups, preclude any valid conclusion, however the results do not suggest
      that Hc concentration or folic acid administration influence the development of
      toxemia of pregnancy.

PMID- 16001752
TI  - Building a reputation.

PMID- 16001753
TI  - Team service.

PMID- 16001754
TI  - Healthy returns.

PMID- 16001755
TI  - Signing on the dotted line.

PMID- 16001756
TI  - Going to market.

PMID- 16001757
TI  - Web wellness.

PMID- 16001758
TI  - Open for business. Interview by Joyce Jensen.

PMID- 16001759
TI  - Strategic innovation.

PMID- 16001760
TI  - Standards for satisfaction.

PMID- 16001761
TI  - A marketing lesson from 9/11?

PMID- 16001763
TI  - Toward a simplified strategy for managing dyspepsia.

PMID- 16001764
TI  - Peptic ulcer and Helicobacter pylori: update on testing and treatment.
AB  - As evidence about the relationship between Helicobacter pylori infection and
      peptic ulcers accumulates, accurate testing and treatment are becoming
      increasingly important. However, big questions remain about the best strategies
      for detecting and managing this infection. In this article, the authors discuss
      the association between H pylori and peptic ulcer disease, the available tests
      for detecting the infection, and the latest treatment strategies for effective
      eradication.

PMID- 16001765
TI  - Gastrointestinal injury from NSAID therapy. How to reduce the risk of
      complications.
AB  - Use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin is
      accompanied by risk of upper and lower gastrointestinal (GI) complications, some
      of which can be serious or even fatal. Management strategies to reduce this risk
      include gastroprotective pharmacotherapy, use of safer NSAIDs, and eradication of
      Helicobacter pylori infection. In this article, Dr Lanas summarizes the GI risks
      associated with NSAID and low-dose aspirin therapy and weighs the efficacy of
      current risk management strategies.

PMID- 16001766
TI  - Androgen replacement in early alcoholic cirrhosis?

PMID- 16001767
TI  - Retinal vascular disease in hypertension. Risk factor modification optimizes
      vision outcomes.
AB  - In a previous article (July 2004, page 57), Dr Colucciello reviewed
      nonproliferative and proliferative diabetic retinopathy. In this article, he
      discusses retinal vascular disease associated with hypertension, which is
      especially likely to occur in persons with vasculopathic risk factors. Retinal
      vein occlusion, retinal arterial macroaneurysm, retinal artery occlusion, and
      carotid artery disease are predictive of progressive systemic vascular disease.
      Modification of risk factors and prompt identification of retinal vascular
      disease optimize vision outcomes and preserve quality of life.

PMID- 16001768
TI  - Erythematous scaling eyelids: patient history, exposure to allergens and
      irritants are keys to diagnosis.

PMID- 16001769
TI  - Lyme disease.

PMID- 16001770
TI  - [Electrocardiograms indicating a potential future sudden death].

PMID- 16001771
TI  - [The state and management of sudden death].
AB  - In Japan, the number of sudden death is estimated to be about 100,000/year and
      60% of them are sudden cardiac death(SCD). And the cause of almost SCD is death
      of arrhythmia. The prevention of SCD by antiarrhythmic drugs is limited. So for
      the high risk group of SCD, ICD is needed. On the other hand, CPR of the
      bystander and the use of AED are important to avoid SCD. We must spread the
      education and training for the citizens.

PMID- 16001772
TI  - [Incidence rate of sudden death in Japan].
AB  - Incidence rate of sudden death differs depending on the definition of the sudden
      death, survey method, and characteristic of the study population. Death
      certificate survey of the regional population revealed the incidence rate of 1 to
      2 per 1000 population per year (definition: natural death occurring within 24
      hours of the symptom onset). When the medical records were reviewed in addition
      to the death certificate and those with malignant neoplasm or bedridden condition
      were excluded, the rate decreased to 0.4. Meta-analysis of cohort studies of the
      rural area and work-site, the incidence rate was reported to be 0.42 in men and
      0.09 in women (age 40 to 69 years). The work-site cohort studies showed smaller
      incidence rate of 0.16 to 0.22 (age less than 60 years) in men due to healthy
      worker's effect.

PMID- 16001773
TI  - [Sudden cardiac death: medico-legal aspects].
AB  - Diagnosis of sudden cardiac death (SCD) is the most important forensic practice
      because of (1) misdiagnosis of extrinsic death as SCD, (2) under-report of
      unusual (unnatural) death, (3) difficulty in diagnosis by autopsy, histology, and
      death-scene investigation, (4) difficulty to judge the contribution of accident,
      violence, psychological stress, over-work, and medical malpractice. Forensic
      pathologists must precisely diagnose the proximal cause of death and determine
      the contribution of extrinsic and intrinsic factors, thereby showing fair proof
      for the legal responsibility of the deceased and concerned party. This article
      reviews these forensic aspects of SCD with reference cases.

PMID- 16001774
TI  - [Pathology of sudden cardiac death].
AB  - Sudden unexpected cardiac death generally occurs in persons with previously
      unrecognized heart disease. It has become evident that it occurs often enough in
      patients without any identifiable structural abnormality. Although mechanical
      cardiac function may seem normal, such patients might have certain discrete
      anatomic abnormalities, such as myocarditis, focal myocardial fibrosis,
      hypertrophy of Purkinje-like myocytes, and myocardial disarray. The
      pathophysiology in patients with acute myocardial infarction (atherothrombosis of
      the coronary arteries) was discussed.

PMID- 16001775
TI  - [Idiopathic cardiomyopathy].
AB  - Cardiomyopathies are defined as diseases of the myocardium associated with
      cardiac dysfunction. They are classified as dilated cardiomyopathy, hypertrophic
      cardiomyopathy, restrictive cardiomyopathy. Dilated cardiomyopathy is
      characterized by dilatation and impaired contraction of the ventricles.
      Hypertrophic cardiomyopathy is characterized by ventricular hypertrophy, which is
      usually asymmetric. Restrictive cardiomyopathy is characterized by restrictive
      filling and reduced diastolic function, with normal systolic function and wall
      thickness. Except for cardiac failure, sudden death from arrhythmia is the
      leading cause of death among cardiomyopathy patients. ACE inhibitors and beta
      blockers are effective medicine for cardiac failure patients. However sudden
      death rate of cardiomyopathy patients is still high. Implantable cardioverter
      defibrillator could save many cardiomyopathy patients from sudden death according
      to a lot of trials.

PMID- 16001776
TI  - [Heart failure and sudden death].
AB  - Sudden death in patients with heart failure (HF) is a topic of great complexity.
      Neurohumoral activation including adrenergic and renin-angiotensin-aldosterone
      system has been a suspected trigger for lethal ventricular arrhythmias and sudden
      deaths. Randomized clinical trials have demonstrated that angiotensin converting
      enzyme inhibitors, angiotensin II receptor antagonists and beta-adrenergic
      blockers improve survivals in patients with HF. Although prophylactic implantable
      cardioverter defibrillator (ICD) therapy is effective reducing mortality in
      patients with left ventricular (LV) systolic dysfunction, the ICD is unlikely to
      be appropriate for all patients with LV systolic dysfunction. In addition, the
      effect of routine prophylactic use of ICDs on health care costs must be carefully
      considered. The care of patients with LV systolic dysfunction should be
      individualized for each patient.

PMID- 16001777
TI  - [Arrhythmias].
AB  - There are several underlying factors including anatomical substrates (coronary
      artery disease, cardiomyopathy, valvular disease, congenital heart disease, WPW
      syndrome) and modulating factors(autonomic nervous system, electrolyte balance,
      drugs) which may induce sudden cardiac death. Although studies evaluating
      mechanisms of sudden cardiac death are increasing, evaluation of risk of each
      patient and effectiveness of preventive treatments are still inadequate. Sudden
      death due to life threatening arrhythmias in the out-of-hospital situation can be
      resuscitated by non-medical staff with automated external defibrillator. In these
      resuscitated high-risk patients implantable cardioverter and defibrillator could
      be used to prevent sudden death due to unpreventable further arrhythmic episodes.
      Widespread availability of automated external defibrillator is mandatory.

PMID- 16001778
TI  - [Long QT syndrome].
AB  - The long QT syndrome (LQTS) is characterized by prolongation of the QT interval,
      causing torsade de pointes and sudden cardiac death. This syndrome can be divided
      into idiopathic (congenital) and acquired forms. The idiopathic form is a
      familial disorder that can be associated with sensorineural deafness (Jervell and
      Lange--Nielsen syndrome, autosomal recessive) or normal hearing (Romano--Ward
      syndrome, autosomal dominant). The acquired form has a long QT interval caused by
      various drugs such as quinidine sotalol and dofetilide, also by noncardiovascular
      drugs such as antihistamine, antibiotics, antipsychotics and others. Also, the QT
      interval is prolonged by electrolyte abnormalities such as hypokalemia and
      hypomagnesemia, central nervous system lesions, significant bradyarrhythmias,
      cardiac ganglionitis, mitral valve prolapse and probucol. DNA variants appearing
      to predispose to drug-associated acquired long QT syndrome have been reported in
      congenital long QT.

PMID- 16001779
TI  - [Sudden death in Rett syndrome].
AB  - Rett syndrome is a unique disorder mainly in girls characterized by global
      deceleration of psychomotor development and subsequent loss of acquired cognitive
      and motor skills, occurring after 6 to 18 months of apparently normal
      development. Previous study described that 26% of the cause of their death was
      sudden and unexpected. Although the cause of sudden death is still unknown,
      respiratory disorder, cardiac arrhythmia, and severe seizure might be related to
      sudden death. The possibility of sudden death should be informed to families of
      patients with Rett syndrome. Electrocardiogram should be examined in older
      patients, because prolongation of QTc and T wave abnormalities increase with
      advancing stage.

PMID- 16001780
TI  - [Williams syndrome].
AB  - Williams syndrome (WS) is a malformation syndrome characterized by cardiovascular
      disease (supravalvular aortic stenosis, peripheral pulmonary stenosis), facial
      dysmorphism and growth/developmental delay, and now is known to be caused by
      deletion of elastin gene and other contiguous genes at chromosome 7. Sudden death
      has been reported in more than 25 patients with WS so far. Bird, et al (1996)
      reported 10 sudden death cases, 6 of which were associated with cardiac
      catheterization. Wessel, et al (2004) estimated the incidence of sudden death to
      be around 1/1000 patient years. Clinical and pathological findings in sudden
      death patients suggest that coronary artery stenosis, ventricular hypertrophy and
      myocardial ischemia are risk factors for sudden death in WS.

PMID- 16001781
TI  - [Brugada syndrome].
AB  - The Brugada syndrome, first described as a new clinical entity in 1992, is
      characterized by ST segment elevation in right precordial leads (V1 to V3) with a
      high risk of sudden death. The clinical presentation of this syndrome is
      distinguished by a male predominance and the appearance of lethal arrhythmic
      events. In 1998, mutation in SCN5A, the alpha-subunit of the sodium channel,
      linked the etiology of this syndrome had been discovered. The proper diagnostic
      criteria has been proposed by the European Society of Cardiology based on the
      currently available clinical data of this syndrome. In the symptomatic patients
      often need an implantable cardioverter defibrillator (ICD) because of a high
      incidence of recurrence.

PMID- 16001782
TI  - [Mitral valve prolapse].
AB  - It is thought that mitral valve prolapse is the most commonly diagnosed valvular
      heart disease and affects 3 to 5% of the community. Mitral valve prolapse is
      commonly a benign disease and the prognosis is good. But it is understood that
      mitral valve prolapse causes sudden death rarely. As etiologies of their sudden
      deaths ventricular arrhythmia, mitral valve regurgitation et al. are known.
      Mitral valve prolapse is brought as the reason of sudden deaths in athletes not a
      little. Therefore, it is important to follow up them by exercise tolerance test,
      Holter ECG, ultrasoniccardiography, and chest auscultation et al. and the
      prescription of beta-blockade et al. and the insertion of implantable
      cardioverter defibrillator are considered. Moreover, it is important to decide
      right or wrong of exercise practice.

PMID- 16001783
TI  - [Sudden death and cardiovascular complications in Marfan syndrome: impact of
      surgical intervention].
AB  - Marfan syndrome is an autosomal dominant disorder of connective tissue
      characterized by abnormalities involving the skeletal, ocular, and cardiovascular
      systems. The cardiovascular complications of the syndrome lead to a reduced life
      expectancy for affected individuals if left untreated. Major cause of death
      include acute aortic dissection, aortic rupture, and sudden death, which resulted
      from congenital vascular fragility. Such life-threatening complications in Marfan
      syndrome can be managed effectively, by routine aortic imaging, beta-adrenergic
      blockade, and prophylactic replacement of the aortic root before the diameter
      exceeds 5.0 to 5.5 mm. Valve preserving aortic root reconstruction yielded
      improved postoperative quality of life compared with Bentall operation, by
      reducing late complications related to anticoagulants. It should be carried out
      before onset of aortic regurgitation for long-term native valve durability.

PMID- 16001784
TI  - [Sudden death due to stroke and its management].
AB  - Subarachnoid hemorrhage and cerebral hemorrhage are the most frequent causes of
      sudden death due to stroke. Brainstem hemorrhage, which is the cause of
      respiratory and vasomotor centers dysfunction, is frequently the direct cause of
      sudden death caused by stroke, and not only cerebral edema, but also secondary
      lethal arrhythmia, myocardial infarction, pulmonary embolism, or asphyxiation by
      dysphagia may be indirect causes of death associated with stroke. To prevent
      sudden death due to stroke, management of respiratory and circulatory systems as
      well as treatment corresponding to the type or severity of the disease are
      required. In this issue, we discuss the cause, management, and prevention of
      sudden death due to stroke.

PMID- 16001785
TI  - [Sudden asthma death: etiology and prevention].
AB  - The duration of the last lethal asthma attack in children was short and their
      asthma deaths were unexpected and abrupt in many cases by the annual reports of
      the committee on asthma death in children of the Japanese Society of Pediatric
      Allergy and Clinical Immunology. In adult asthma death, sudden death type died in
      three hours 29.3%, unstable sudden aggravation type 16.2% and status asthmatics
      was only 21.2% by the national wide study in Japan. The severity of asthma prior
      to asthma death; in children mild was 26%, moderate 30%, severe 43% and in adult,
      mild was 9.3%, moderate 41.4% and severe 49.2%. Asthma deaths during sports were
      also discussed. In adolescent and young adult, asthma was one of the main causes
      of sudden death. Prevention of sudden asthma death was discussed.

PMID- 16001786
TI  - [Sleep apnea syndrome].
AB  - Obstructive sleep apnea syndrome (OSAS) is strongly associated with
      cardiovascular disease which means these patients could suffer sudden death from
      these cardiovascular diseases, but it is a rare case that common OSAS itself
      causes sudden death directly. On the other hand, we never wrongly diagnose
      serious sleep-related breathing disorders (SBDs) such as sleep hypoventilation
      syndrome, OSAS patients with cardiovascular disease (i.e. ischemic heart disease,
      cardiac arrhythmia and cardiac failure) and bilateral vocal cord paralysis caused
      by multiple system atrophy as common OSAS. This section describes how to
      distinguish these SBDs from common OSAS.

PMID- 16001787
TI  - [Aortic aneurysm].
AB  - Thoracic and abdominal aortic aneurysms have potential risk of sudden death,
      because they have a tendency of rupture. The risk of rupture is high, if they are
      saccular type or the diameters of them are large enough. Acute aortic dissection
      has a high risk of sudden death due to cardiac tamponade, if the dissection
      involves the ascending aorta.

PMID- 16001788
TI  - [Sudden death from acute pulmonary thromboembolism].
AB  - Acute pulmonary thromboembolism has been a common illness even in Japan and gets
      increased social as well as medical attention, especially during postoperative
      period. A current problem associated with mortality in this disease is a high
      incidence of sudden death. Effective ways of reducing unexpected death are to
      educate medical staffs about risk factors and triggers of this disease and to
      institute a comprehensive institutional policy of primary prophylaxis in patients
      at risk. Since it will be inappropriate to assume that the results of western
      studies are fully applicable to the clinical situation in Japan, future task in
      this disease is collection of Japanese own evidences.

PMID- 16001789
TI  - [Sudden death while bathing].
AB  - We describe the epidemiologic and pathophysiologic features of sudden death while
      bathing. The leading cause of death is cardiovascular disease (60.4%), followed
      by cerebrovascular disease (18.7%) and drowning (11.2%). Because hydrostatic
      pressure, autonomic nervous reflexes or endocrine system reflect on hemodynamic
      changes while bathing, the elderly persons or patients with cardiovascular
      disease are often suffered from fatal cardiac events. To find the detail
      pathophysiologic changes while bathing, exact cause of death should be examined
      by autopsies. Furthermore, elderly or handicapped persons should be supervised by
      their families for preventing drowning.

PMID- 16001790
TI  - [Sudden cardiac death during exercise in the elder persons].
AB  - Sudden cardiac death during exercise is consequent on the myocardial infarction
      which is caused by acute coronary occlusion, triggered by the rupture of unstable
      plaque due to temporary exercise hypertension in the hyper-coagulable conditions
      induced by dehydration and increased sympathetic activity. Fortunately, most
      cases were witnessed by audience and could be saved the life with AED. The elder
      persons should have medical checks in which the coronary risk factors are
      evaluated before aerobic exercise. Mild exercise such as spinal stretch walking
      is recommended to the elder persons with multiple coronary risk factors.

PMID- 16001791
TI  - [Karoshi, death by overwork].
AB  - Karoshi (death by overwork) is one of social medical terms, which used by
      survivors of victims who attacked with cardiovascular diseases such as stroke,
      myocardial infarction and sudden cardiac death. In Dec. 2000, Compensation
      Standard of cardiovascular diseases in Workers' Insurance was changed and
      admitted the relationship between chronic fatigue and cardiovascular attacks. As
      a result, compensation numbers of Karoshi attributed to three hundred and more
      from about 80 cases. The Ministry of Health, Labour and Welfare thinks that most
      of Karoshi caused by long working hours continuing for several months, especially
      without payment, so that the Labour Standard Inspector Office requests to
      decrease overtime work more than 45 hours per month to firm administrators.

PMID- 16001792
TI  - [Sudden infant death syndrome].
AB  - The Disability-SIDS Research Committee, Ministry of Health and Welfare defines
      sudden infant death syndrome (SIDS) as "a syndrome that causes sudden death of an
      infant in which the demise of the victim cannot be anticipated by his prior
      health status or medical history and the cause of death cannot be determined from
      the circumstances surrounding the final moment or from the results of an
      autopsy". A diagnostic autopsy is obligatory. SIDS brings a profound
      psychological shock to the victim's family. If the incidence takes place at a
      nursery or a certain medical facility (such as that involved in delivery), it may
      develop into a civil or criminal case related to professional responsibility for
      placing the infant in a prone position or a possible fault in nursing care. The
      current study describes the epidemiology, pathogenesis, and physiopathology of
      SIDS, as well as prospects for its prevention and related social problems.

PMID- 16001793
TI  - [Sudden cardiac death of school-age children].
AB  - Approximately 60 to 80 cases of childhood sudden death occur under school
      supervision every year in Japan and about 71% of them are sudden cardiac death.
      The incidence of sudden death among school-age children increases with age. 0.3
      per 100,000 for elementary schoolchildren, 0.8 per 100,000 for junior high school
      children and 0.9 per 100,000 for high school children, approximately. Boys are
      remarkably more prone to sudden death than girls. Cardiac sudden death is often
      related to physical exercise and 70% of cases occur during running exercise.
      Although it is usually difficult to prevent the actual occurrence of sudden
      cardiac death, efforts to decrease sudden cardiac death should be reinforced by
      the cardiac screening examination and by ensuring in cooperation with children
      themselves, their parents, school staffs, and medical professionals. In
      particular, it is recommended that all teachers at junior high schools and high
      schools should have more knowledge about diseases related to sudden death.

PMID- 16001794
TI  - [The genetic disorders responsible for sudden cardiac death].
AB  - Sudden cardiac death is defined as an unpredictable death within 24 hours. It is
      estimated to occur with a frequency of more than 50,000 per year in Japan. The
      inherited arrhythmogenic diseases associated with the transmembranous ionic
      channels, anchoring proteins or intracellular calcium regulating proteins are
      thought to be responsible for sudden cardiac death in infants, children, and
      young adults who have structurally normal hearts. Recent genetic analyses have
      identified congenital diseases such as the long-QT syndrome (LQTS), the Jervell
      and Lange-Nielsen syndrome (JLNS), the Brugada syndrome (BrS), the short-QT
      syndrome (SQTS), the arrhythmogenic right ventricular cardiomyopathy type 2
      (ARVC2), and the catecholamine-induced polymorphic ventricular tachycardia (CPVT)
      /familial polymorphic ventricular tachycardia (FPVT). Loss of function in the
      slow component of the delayed rectifier potassium current (I(Ks)) channels
      (KCNQ1, KCNE1), the rapid component of the potassium current (I(Kr)) channels
      (KCNH2, KCNE2) and the inward rectifier potassium current (I(Kl), Kir2.1) channel
      (KCNJ2) is linked to the LQTSs (type 1, 2, 5, 6, and 7 (Andersen syndrome)) and
      the JLNSs (type 1 and 2). Changes of function in the alpha-subunit of cardiac
      sodium channels (SCN5A) is also linked to the LQTS type 3 and the BrS. A mutation
      in the ankyrin-B, anchoring proteins, has been identified as cause of the LQTS
      type 4. The SQTS is caused by gain of function in the KCNH2. Further, the
      missense mutations in the gene encoding ryanodine receptor 2 (RyR2) or
      calsequestrin 2 (CASQ2) that regulate intra-cardiac calcium handling is possibly
      implicated in the ARVC2 and the CPVT/FPVT. Herein, we present a review of the
      literature regarding the genetic mechanisms of the inherited arrhythmogenic
      diseases.

PMID- 16001795
TI  - [Gender difference of sudden death].
AB  - The survey of sudden death (SD), defined as death within 24 hours from the onset
      of underlying cause, was conducted in Niigata. The survey was based on all
      summary death certificates for the period 1984 to 1986. The underlying cause was
      divided into 4 groups: acute myocardial infarction (AMI), cerebrovascular
      accident (CVA), other circulatory diseases (OCD) and non-circulatory disease
      (NCD). The SD incidence ratio of male to female was 1.7, 1.3, 1.3, and 1.5 for
      AMI, CVA, OCD, and NCD, respectively. OCD accounted for 50.1% of underlying
      causes in male and 53.1% in female. The proportion of OCD cases with histories of
      diseases related to atherosclerosis (e.g. hypertension, diabetes, etc) increased
      with age in both sexes, accounting for 38.5% in male and 36.4% in female aged 75
      years old or over.

PMID- 16001796
TI  - [Therapeutic application of RNA interference].
AB  - The discovery that small double stranded RNAs mediate RNA interference in
      mammalian cells opened the way to the therapeutic use of siRNA. siRNA has the
      properties well suitable for medicine, which of high selectivity, high efficacy
      with low dose and natural components of cells. While siRNAs are expected to be
      epoch-making new drugs, such as a biotech-based medicine, there are several
      problems concerning side effects and bioavailability to be solved, such as
      interferon response, off-target activity and short half-life in blood
      circulation. Here, I will discuss with problems that face therapeutic application
      of RNA interference.

PMID- 16001797
TI  - [Therapeutic approaches to non-erosive GERD--comparison between the Western
      countries and Japan].
AB  - Some patients with heartburn may not show endoscopic evidence of esophagitis.
      They were called as "endoscopy-negative GERD", "non-erosive reflux disease
      (NERD)" or "symptomatic-GERD". Symptom of heartburn might be more severe in
      Europe and United States when compared to those in Japan. NERD patients seem to
      be more resistant to pharmaco-therapy and surgical procedures, and it seems to be
      more prominent in patients in the Western countries than those in Japan.
      Differences between the Western countries and Japan might be based on the
      difference of the diet habit, but the contamination of functional
      gastrointestinal disorders might be also involved.

PMID- 16001798
TI  - [Mitochondrial dynamics regulated by fusion and fission].

PMID- 16001799
TI  - [MTH1, an oxidized purine nucleoside triphosphatase suppresses mitochondrial
      dysfunction and cell death caused by oxidative stress].

PMID- 16001800
TI  - [Molecular mechanism of exocytosis in secretory gland].

PMID- 16001801
TI  - [Mechanism of CO2-responsive transcriptional regulation in photosynthetic
      organisms: carbon-concentrating mechanism in a green alga, Chlamydomonas
      reinhardtii].

PMID- 16001802
TI  - [Evolutionary genomics confirmed Darwin's selfing model: an adaptation revealed
      by DNA analysis].

PMID- 16001803
TI  - [How the methyl-CpG binding protein-related epigenetic disease turns on the genes
      that produce its symptoms].

PMID- 16001804
TI  - [Research ethics in biotechnology ].

PMID- 16001805
TI  - [Specific induction of neurons and Schwann cells from bone marrow stromal cells
      and application to neurodegenerative diseases].

PMID- 16001806
TI  - [Trans-choroidal fissure approach to the third ventricle and perimesencephalic
      cisterns].

PMID- 16001807
TI  - [Interventional neuroradiology in USA].

PMID- 16001808
TI  - [Clinical study of multiple traumas with severe facial injury undergoing
      emergency endovascular treatment: significance of emergency embolization of the
      external carotid artery].
AB  - The outcome of multiple injures freqently depends on the priority of treatments,
      and the decision as to the procedures and timing of primary care is extremely
      important. We studied the patients with multiple trauma whounderwent emergency
      endovascular treatment for facial hemorrhage related to external carotid arterial
      injury. The subjects are 5 patients who underwent embolization of the external
      carotid artery by an endovascular approach among patients with multiple traumas
      who were brought to our hospital by ambulance. In these patients, the vital signs
      on arrival, interval between injury and intravascular surgery, type of brain
      injury, type and grade of concurrent injury and outcome were studied. Three
      patients showed hemorrhagic shock on arrival, and 1 patient showed hemorrhagic
      shock immediately after arrival. The mean interval between injury and
      endovascular surgery was 3.9 hours. All patients had skull base fracture, and
      abnormal intracranial lesions on initial CT including 4 focal injuries and 1
      diffuse injury. Moderate to severe thoracic/abdominal injuries were noted in 3
      patients. In the remaining 2 patients, there was no trauma in the thoracic or
      abdominal regions. Intraperitoneal hemorrhage with splenic injury was observed in
      3 patients. In 3 of 4 patients died by hemorrhagic shock because of the delay of
      endvascular treatments. In trauma patients with persistent hemorrhage, emergency
      endovascular treatment should be considered as a primary survey for initial
      treatment without delay under intensive conservative treatment.

PMID- 16001809
TI  - [Three-dimensional atlas of subthalamic nucleus and its adjacent structures].
AB  - The deep brain stimulation (DBS) is an effective treatment modality of the
      functional neurosurgery for disorders such as Parkinson's disease, essential
      tremor and generalized dystonia. Recently, the targets of DBS for treatment of
      Parkinson's disease are the thalamus, the Globus pallidus and subthalamic nucleus
      (STN). The STN-DBS induces improvements in axial motor fluctuation and the on-off
      phenomenon. The important problem for STN-DBS is that DBS is inserted properly
      into the STN for good results. The STN is a small body in the deep brain
      structures. We cannot understand the STN clearly because of its small size and
      complex shape. The topographical information of deep brain structures has been
      essential for accurate stereotactic placement of the stimulating electrode of
      DBS. The target of a deep brain structure is based on the Schaltenbrand and
      Wahren atlas (S-W atlas). The S-W atlas consists of two-dimensional images such
      as a coronal section. For this reason, it is difficult to understand localization
      and the shape of deep brain structures spatially, especially of the subthalamic
      nucleus on S-W atlas. The three-dimensional image is a useful tool for diagnosis
      and preoperative planning, because it can easily give neurosurgeons the vivid
      spatial image of complex structures. We studied a practical use of a three
      dimensional atlas of deep brain structures in functional neurosurgery. We devised
      a three-dimensional atlas to see an image at a free angle on a personal computer.
      It provided us with more useful information about structures than ones by two
      dimentional images. Three-dimensional atlas also helped us make a decision for
      placement of the deep brain electrode and appropriate electrophysiological
      recording.

PMID- 16001810
TI  - [Basal interhemispheric approach for distal anterior cerebral aneurysms].
AB  - PURPOSE: To investigate retrospectively the usefulness of basal interhemispheric
      approach for neck clipping of aneurysms located on genu or infracallosal portion
      of anterior cerebral artery. CLINICAL MATERIALS AND METHODS: Seventeen aneurysms
      in 17 patietns treated by clipping with basal inter-hemispheric approach in our
      department for past 8 years were reviewed. Of them, 12 were ruptured aneurysm and
      5 were unruptured one. The distance between frontal base and most frontally
      located bridging vein and the shortest distance from cranium to aneurysm were
      measured from angiograms of lateral view, and the point on cranium of the
      shortest distance was identified in each cases. Bridging vein damage suffered
      during surgical approach and the duration of brain retractor use were examined
      from operative videotapes. The clinical outcome was rated at discharge by
      Modified Rankin Scale. RESULTS: The distance between frontal base and most
      frontally located bridging vein was ranged as 15-69 mm (mean, 32 mm). The
      shortest distance between cranium and aneurysm in each case was ranged as 25-48
      mm (mean, 33 mm), and the point on cranium of the shortest distance was these
      within 20 mm from frontal base in 11 cases. Any damage or cut of bridging vein
      were not seen in all cases. The duration of brain retractor for unilateral
      frontal lobe and for bifrontal lobe in recent 14 cases was ranged 0-46 minutes 41
      seconds (mean, 8 minutes 55 seconds) and 0-16minutes (mean, 2minutes 24 seconds),
      respectively. No brain damage caused by operative procedure was detected on
      postoperative CT scan. All five patients of unruptured one and 8 patients of
      ruptured one were rated as 0 by Modified Rankin scale, 2 patients of ruptured one
      as 3 and 5, and 2 patients of ruptured one died. CONCLUSION: The basal
      interhemispheric approach for neck clipping of aneurysm located on genu or
      infracallosal portion of anterior cerebral artery would provide wide view of
      aneurysm and its surrounding structures with minimum retraction of frontal lobe,
      short distance to the aneurysm, and low risk of bridging vein damage.

PMID- 16001811
TI  - [Non-cardiogenic pulmonary edema induced by non-ionic radiographic contrast media
      during the coil embolization for a ruptured cerebral aneurysm].
AB  - We describe a 48(correction of 44) year-old woman, who presents a non-cardiogenic
      pulmonary edema caused by non-ionic radiographic contrast medium. She suffered
      from subarachnoid hemorrhage due to dissecting aneurysm of right vertebral
      artery. Cerebral angiography followed by coil embolization for the aneurysm was
      performed. During the interventional procedure, saturation of blood oxygen
      suddenly declined and chest X-ray photography obviously revealed pulmonary edema.
      At first we dealt with it as neurogenic phenomenon but subsequently interpreted
      it to non-cardiogenic pulmonary edema induced by radiographic contrast medium,
      since intra-arterial injection of contrast medium at follow-up angiography led
      the symptoms into more fulminant status. Intensive care including endotracheal
      intubation and continuous positive airway pressure ventilation consequently
      achieved complete remission and the patient discharged without any sequelae.
      Although low osmolar, non-ionic contrast medium has been regarded as relatively
      safe, severe reaction such as dyspnea, hypotension and cardiac arrest could
      emerge at certain intervals. We must perceive the adverse effects of it because
      the usage of contrast medium will dramatically increase with development of
      diagnostic radiographical methodology and interventional neurosurgery.

PMID- 16001812
TI  - [A case of intracranial neurinoma arising from the maxillary branch of the
      trigeminal nerve].
AB  - The intracranial portion of the trigeminal branches is rarely involved in
      neurinomas. The clinical characteristics including symptoms, neuroradiological
      findings and results of surgical excision of the previously reported 11
      neurinomas and the present case arising from the intracranial trigeminal branches
      are reviewed. A 59-year-old female patient complained of paresthesia and
      hypesthesia in the infraorbital region with no other neurological abnormalities.
      Neuroradiological examinations revealed a round cyst-like tumor located at the
      middle fossa with enlargement of the foramen rotundum and pterygopalatine fossa.
      No vascular abnormalities were found by angiography. At surgery, the solid tumor
      with no cystic component arising from the intracranial maxillary nerve was
      removed totally via a frontotemporal extradural and interdural approach with
      zygomatic osteotomy. Histopathology revealed a typical neurinoma. The paresthesia
      disappeared following surgery. Clinical features of neurinomas arising from the
      trigeminal branches are varied but distinct depending upon the site of origin of
      the tumors. These tumors can be removed totally in most cases through the
      extradural and interdural approach without critical morbidity. Special care
      should be taken not to cause injuries to the surrounding neurovascular structures
      such as cranial nerves and internal carotid artery. A small amount of residue is
      acceptable in cases of tumors with tenacious adhesion to these critical
      structures.

PMID- 16001813
TI  - [Primitive neuroectodermal tumor arising 8 years after chemotherapy and
      radiotherapy for acute lymphoblastic leukemia: case report].
AB  - We report a case of primitive neuroectodermal tumor (PNET) arising 8 years after
      chemotherapy and radiotherapy for acute lymphoblastic leukemia. A 15-year-old boy
      with a history of acute lymphoblastic leukemia, at the age of 7, underwent
      chemotherapy and 14Gy of radiotherapy to the whole brain. He was admitted to our
      department due to the development of aphasia, right hemiparesis and generalized
      convulsive seizure. MRI showed an irregularly enhanced mass in the left frontal
      lobe. A gross total removal of the tumor was performed and histological
      examination showed it to be PNET. Postoperatively, the patient underwent 20Gy of
      radiotherapy to the whole brain and 42Gy of local radiotherapy. Follow-up MRI
      showed no evidence of recurrent tumor 4 months after the radiotherapy. This tumor
      was thought to be a secondary brain tumor arising in this survivor of childhood
      acute lymphoblastic leukemia and it is a rare complication of successful leukemia
      treatment.

PMID- 16001814
TI  - [Spontaneous umbilical fistula as a complication of ventriculo-peritoneal shunt:
      case report].
AB  - We report a rare case of a spontaneous umbilical fistula as a complication of
      ventriculo-peritoneal shunt. A 36 year-old male was admitted our hospital
      complaining serous discharge from the umbilicus. Two years before admission, he
      underwent ventriculo-peritoneal shunt for the hydrocephalus due to right
      hypertensive intracranial hematoma and intraventricular hemorrhage. A shuntgraphy
      was done and it revealed the cerebrospinal fluid leakage from the umbilicus
      through an urachal remnant. The abdominal shunt tube was removed at the surgery,
      and the patient was discharged uneventfully without shunt revision. The possible
      etiology of this rare complication in this case was supposed to be due to the
      persistence of the urachus.

PMID- 16001815
TI  - Gender-based nursing care.

PMID- 16001816
TI  - Effects of hyperglycemia on neurologic outcome in stroke patients.
AB  - Hyperglycemia in acute stroke patients increases cerebral infarct size and
      worsens neurologic outcome with and without preexisting diabetes mellitus.
      Hyperglycemia results from metabolic alterations in glucose metabolism, and is
      most common in patients with acute illness such as stroke. Strict control of
      hyperglycemia with intensive insulin therapy has been shown to dramatically
      decrease hospital morbidity and mortality, inpatient stays, hospital costs, and,
      most importantly, neurologic injury. Insulin treatment protocols developed and
      implemented by multidisciplinary teams allow for rapid and effective control of
      hyperglycemia. Nurses who know about hyperglycemia's often-neglected and
      detrimental effects can play a vital role in influencing outcomes in stroke
      patients.

PMID- 16001817
TI  - Electroencephalogram abnormalities in children with autism spectrum disorders.
AB  - Children with an autism spectrum disorder (ASD) often are evaluated with
      electroencephalogram (EEG) studies to assess their risk for seizures or other
      underlying abnormalities. Their risk is estimated at 7% - 42%. EEG studies were
      conducted on a subgroup of children while following established practice
      parameters for evaluating children for ASD. Abnormal EEG results were obtained in
      85 (27%) of the 316 children evaluatedfor ASD. Within the subset of abnormal
      results, 64 children had autism, 10 had an ASD or milder presentation, 6 had
      another developmental disorder, 3 had Rett syndrome, had Down syndrome, and 1 had
      Wolf-Hirshhorn syndrome. The abnormal EEG findings included epileptiform
      abnormalities in 55 patients (65%), and slowing in only 13 patients (15%). The
      focality of the epileptiformfindings included 26 (30%) in the temporal areas, 24
      (28%) in the central area, 20 (23%) in the frontal area, and 7 (8%) in the
      occipital area. These findings confirm the importance of ongoing medicalfollow-up
      for children with ASDs, especially for those with abnormal EEG results.

PMID- 16001818
TI  - Using the BIS monitor in palliative care: a case study.
AB  - The majority of deaths occur in the hospital setting, and of these deaths, 20%
      are in an intensive care unit (ICU). Care provided on the ICU shifts from
      curative to palliative when a patient's death appears to be imminent. Nursing
      care decisions made at the end of life are critical to the experience of the
      patient, and leave a lasting impression on the patient's family and the nurses
      involved in providing care. One of the main concerns of family members during
      this time is the comfort of their loved one. Assessing comfort can be especially
      difficult in the patient who is unresponsive. One tool that can assist the nurse
      in the assessment and management of analgesic effectiveness is the Bispectral
      (BIS) Index Monitor. As the use of BIS monitoring grows in the ICU setting, more
      information will be available that will help all involved in the palliative care
      process ensure patients have a peaceful death.

PMID- 16001819
TI  - Not your "typical patient": cryptococcal meningitis in an immunocompetent
      patient.
AB  - Meningitis, when caused by the fungal mycoses Cryptococcus neoformans, is
      normally seen in immuno-compromised hosts. However, immunocompetent patients are
      also susceptible to cryptococcal meningitis (CM). In patients with an intact
      immune system, CM usually presents with the typical signs and symptoms of
      meningitis: fever, stiff neck, and headache. Major implications for the primary
      and advanced practice nursing plans of care for CM patients include a thorough
      history and physical exam, early diagnosis and treatment, and an individualized
      plan of care focused on minimizing sequelae and side effects of treatment and
      maximizing functional recovery.

PMID- 16001820
TI  - Obstructive sleep apnea in neurological patients.
AB  - Obstructive sleep apnea (OSA) is a serious condition that is common among
      neurological patients. If undiagnosed and untreated, it may lead to hypertension,
      coronary heart disease, pulmonary hypertension, myocardial infarction, stroke,
      psychiatric disorders, cognitive impairment, and, ultimately, death. One of the
      first steps in identifying OSA is to recognize its signs and symptoms. Nursing
      knowledge of OSA facilitates referral, diagnosis, and treatment of this
      potentially life-threatening condition.

PMID- 16001821
TI  - Neurofibromatosis type 2-living with the complications: a case study.
AB  - Neurofibromatosis is a disease caused by a chromosomal defect that can occur
      spontaneously or be inherited. The disease is grossly disfiguring and carries
      with it significant psychological sequelae. It is characterized by tumors on
      nerve sheaths that can arise anywhere in the body. The rate and frequency of
      occurrence is unpredictable. More than nine different types of neurofibromatosis
      have been identified, but other than types 1 and 2, they are quite rare. All
      types of neurofibromatosis persist for a lifetime, so nurses from different
      backgrounds may encounter such a patient for various reasons. Nursing care should
      focus not only on the medical issues the patient presents with, but also on the
      psychosocial needs that may arise.

PMID- 16001822
TI  - Neuroleptic malignant syndrome in a patient with Parkinson's disease: a case
      study.
AB  - Neuroleptic malignant syndrome (NMS) is a potentially lethal condition that has
      been described in patients with idiopathic Parkinson's disease (PD) after long
      term dopaminergic medications are suddenly stopped or moderately decreased. If
      patients with PD develop severe rigidity, stupor, and hyperthermia, L-Dopa
      withdrawal should be suspected and the dopaminergic drug restarted as soon as
      possible to prevent rhabdomyolysis and renal failure. Nurses who are
      knowledgeable about NMS can provide prompt identification of the PD patient's
      condition and prevent a potentially lethal cascade of symptoms.

PMID- 16001823
TI  - Understanding adolescents: a guide for researchers.
AB  - The research establishment often has a "one size fits all" mentality with regard
      to the research process (Broome, Richards, & Hall, 2001). Consent processes are
      standardized, and federal regulations have been established to protect both
      adults and children. As a research population, however, adolescents often are
      conceptualized as children. Adolescents represent a vulnerable study population.
      To effectively and ethically involve adolescents in research, researchers must
      understand and integrate knowledge of the variability in physical, cognitive, and
      psychosocial developmental factors, as well as an understanding of the research
      processes needed to protect adolescents. Adolescents need to be active
      participants in the decision-making process (e.g., assent/consent, knowledge of
      the risks and benefits, etc.). Researchers must be aware of and accountable for
      the power they hold in influencing adolescents' decisions to participate in
      research, and they must bear in mind that the voluntary and informed consent
      principles may be easily and inadvertently violated (Nelson & Rushton, 2001).

PMID- 16001824
TI  - Specific features of the contact history of probable cases of severe acute
      respiratory syndrome.
AB  - OBJECTIVE: To describe the specific features of the contact history of probable
      cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS: Data of
      SARS cases notified from the Beijing Municipal Center for Disease Control and
      Prevention (BCDC) and supplemented by other channels were collected. All the data
      were analyzed by descriptive epidemiology. RESULTS: (1) The number of probable
      cases with contact history was significantly higher than the excluded cases. (2)
      The proportion of probable cases with contact history descended with epidemic
      development, but this situation did not occur in health care workers (HCWs). (3)
      The fatality rate of probable cases with contact history was significantly higher
      than the cases without contact history (OR = 1.489). (4) The proportion of
      probable cases with contact history was 85.86% among health care workers, which
      was significantly higher than that of non-health care workers (85.86% v.s.
      56.44%, OR=4.69). CONCLUSIONS: (1) The susceptible persons with contact history
      may not get infected, and the contact history is just a sufficient condition of
      infecting SARS; (2) There are 3 conceivable reasons for the descending trend of
      the proportion in probable cases with contact history; (3) The contact history is
      one of the risk factors of the death of SARS cases; (4) The risk of contacting
      with SARS among health care workers is approximately 5 times higher than that of
      non-HCWs.

PMID- 16001825
TI  - Slurry-phase biological treatment of nitrophenol using bioaugmentation technique.
AB  - OBJECTIVE: To investigate the performance of soil-slurry bioreactor used for
      remediating contaminated soil with 4-nitrophenol (4-NP). METHODS: The slurry
      bioreactor was used to degrade different concentrations of 4-nitrophenol with or
      without inoculating the acclimated activated sludge. HPLC system (Hewlett-Packard
      model 5050 with a UV detector) was used for the quantification of 4-nitrophenol.
      RESULTS: The indigenous microorganisms exhibited a little activity for simulated
      soil with 50 mg 4-NP/kg soil. However, at the concentration of 10 mg 4-NPkg soil,
      a considerable degradation occurred within two weeks. It appeared that high
      concentrations of 4-nitrophenol apparently produced an inhibitory effect on
      microbial activity. For system receiving 50 mg 4-NP/kg soil, the maximum rate of
      4-NP degradation measured in the reactor inoculated with 25 g sludge/kg soil was
      approximately 10 times higher than the uninoculated reactor, suggesting that the
      degradation rate of 4-nitrophenol could be enhanced greatly by means of
      inoculating acclimated sludge. CONCLUSION: The addition of sludge capable of
      degrading 4-nitrophenol can result in enhance the degradation rate of 4
      nitrophenol.

PMID- 16001826
TI  - Development of a new sampling medium for bioaerosols.
AB  - OBJECTIVE: To develop a new sampling medium for detecting of bioaerosols.
      METHODS: The sampling media were tested by using Escherichia coli, Staphylococcus
      aureus and Serratia marcescens under static and active conditions, preliminary
      applications were performed using AGI-10 and high volume sampler. RESULTS: The
      average recovery rates were raised to 24.7%, 58.2%, 40.5%, 44.1%, 20.5%, and
      15.4%, respectively in six consecutive experiments under static condition for 60
      min at room temperature. Four kinds of sampling media were singled out after
      static experiments, which were referred to as "samplutions" PD1, PX2, TD1, and
      TX2, respectively. Under the active condition, the protective efficacy of PD1,
      PX2, TD1, and TX2 was 226% (153/47), 553% (111/17), 150% (120/48), and 268%
      (419/114), respectively. CONCLUSION: The samplutions have some effects on the
      subsequent nucleic acid detection, which could be avoided by employing standard
      nucleic acid extraction procedure. The newly developed samplution can be applied
      to the detection of bioaerosols.

PMID- 16001827
TI  - A novel approach of low-frequency ultrasonic naked plasmid gene delivery and its
      assessment.
AB  - OBJECTIVE: To deliver the naked genes into cells through the bioeffects of cell
      membrane porous produced by low-frequency ultrasound (US) and to investigate the
      safety by determining the threshold of cell damage and membrane permeability.
      METHODS: The suspension of red cells from chickens, rabbits, rats, and S180 cells
      was exposed to calibrated US field with different parameters in still and flowing
      state. Laser scanning confocal microscopy, fluorescent microscopy, scanning
      electron microscopy, flow cytometry and spectrophotometry were used to examine
      cell morphology, membrane permeability, enzymes, free radicals, naked gene
      expression efficiency, threshold of cell damage and cell viability. RESULTS: The
      plasmid of green fluorescent protein (GFP) as a reporter gene was delivered into
      S180 cells under optimal conditions without cell damage and cytotoxicity. The
      transfection rate was (35.83 +/- 2.53)% (n = 6) in viable cells, and the cell
      viability was (90.17 +/- 1.47)% (n = 6). Also, malondialdehyde, hydroxyl free
      radical, alkaline phosphatase, and acid phosphatase showed a S-shaped growth
      model (r = 0.98 +/- 0.01) in response to the permeability change and alteration
      of cell morphology. The constant E of energy accumulation in US delivery at 90%
      cell viability was an optimal control factor, and at 80% cell viability was the
      damage threshold. CONCLUSION: US under optimal conditions is a versatile gene
      therapy tool. The intensity of GFP expression in US group has a higher
      fluorescent peak than that in AVV-GFP group and control group (P < 0.001). The
      optimal gene uptakes, expression of gene and safety depend on E, which can be
      applied to control gene delivery efficiency in combination with other parameters.
      The results are helpful for development of a novel clinical naked gene
      therapeutic system and non-hyperthermia cancer therapeutic system.

PMID- 16001828
TI  - Rice from mercury contaminated areas in Guizhou Province induces c-jun expression
      in rat brain.
AB  - OBJECTIVE: Mercury (Hg), as one of the priority pollutants and also a hot topic
      of frontier environmental research in many countries, has been paid higher
      attention in the world since the middle of the last century. Guizhou Province (at
      N24 degrees 30'-29 degrees 13', E103 degrees 1'-109 degrees 30', 1 100 m above
      the sea level, with subtropical humid climate) in southwest China is an important
      mercury production center. It has been found that the mercury content in most
      media of aquatics, soil, atmosphere and in biomass of corns, plants and animals,
      is higher than the national standard. The present study aims to explore the
      influence of mercury pollution on the health of local citizens. METHODS: The
      effect of rice from two mercury polluted experimental plots of Guizhou Province
      on the expression of c-jun mRNA in rat brain and c-jun protein in cortex,
      hippocampus and ependyma was observed using reverse transcription polymerase
      chain reaction (RT-PCR) and immunocytochemical methods. RESULTS: The results
      showed that the mercury polluted rice induced expression of c-jun mRNA and its
      protein significantly. Selenium can reduce Hg uptake, an antagonism between
      selenium and mercury on the expression of c-jun mRNA and c-jun protein.
      CONCLUSION: c-jun participates in the toxicity process of brain injury by mercury
      polluted rice, the expression of c-jun mRNA in brain, and c-jun protein in rat
      cortex and hippocampus can predict neurotoxicity of mercury polluted rice. People
      should be advised to be cautious in eating any kind of Hg-polluted foods. To
      reveal the relationship between c-jun induction and apoptosis, further
      examinations are required.

PMID- 16001829
TI  - Resting energy expenditure and its relationship with patterns of obesity and
      visceral fat area in Chinese adults.
AB  - OBJECTIVE: To investigate the relationship between resting energy expenditure
      (REE) and patterns of obesity/regional fat parameters in Chinese adults. METHODS:
      Body mass index (BMI), fat mass (FM), fat-free mass (FFM) were assessed in 109
      Chinese adults (52 men and 57 women), and their abdominal visceral adipose tissue
      area (VA) and subcutaneous fat area (SA) were measured using magnetic resonance
      imaging (MRI) measurements. REE was measured with indirect calorimetry and
      compared with normal and obese subjects. Multivariate analysis was used to study
      the factors related to REE. RESULTS: The resting energy expenditure per kilogram
      of body weight (REE/kg) was closely related with the area of abdominal visceral
      fat measured with MRI. REE/kg was significantly lower in overweight/obesity
      subjects than in normal-weighted subjects, and significantly lower in subjects
      with abdominal obesity (VA > or = 100 cm2) than in subjects with non-abdominal
      obesity (VA < 100 cm2, BMI > or = 25 kg/m2). In the stepwise regression analysis
      of REE/kg on regional fat parameters, VA in men and women and SA in women were
      independent factors reversely related to REE/kg. CONCLUSION: REE/kg is associated
      with the visceral fat area and more prominent in men. REE/kg can be used as an
      index in the pathophysiology of intra-abdominal obesity.

PMID- 16001830
TI  - Effects of fenvalerate on steroidogenesis in cultured rat granulosa cells.
AB  - OBJECTIVE: This study was designed to examine the in vitro effects of fenvalerate
      on steroid production and steroidogenic enzymes mRNA expression level in rat
      granulosa cells. METHODS: Using primary cultured rat granulosa cells (rGCs) as
      model, fenvalerate of various concentrations (0, 1, 5, 25, 125, 625 micromol/L)
      was added to the medium for 24 h. In some cases, optimal concentrations of 22(R)
      hydroxycholesterol (25 micromol/L), Follicle stimulating hormone (FSH, 2 mg/L),
      or 8-Bromo-cAMP (1 mmol/L) were provided. Concentrations of 17 beta-estradiol(E2)
      and progesterone (P4) in the medium from the same culture wells were measured by
      RIA and the steroidogenic enzyme mRNA level was quantified by semi-quantitative
      RT-PCR. RESULTS: Fenvalerate decreased both P4 and E2 production in a dose
      dependent manner while it could significantly stimulate rGCs proliferation. This
      inhibition was stronger in the presence of FSH. Furthermore, it could not be
      reversed by 22(R)-hydroxycholesterol or 8-Bromo-cAMP. RT-PCR revealed that
      fenvalerate had no significant effect on 3 beta-HSD, but could increase the
      P450scc mRNA level. In addition, 17 beta-HSD mRNA level was dramatically reduced
      with the increase of fenvalerate dose after 24 h treatment. CONCLUSION:
      Fenvalerate inhibits both P4 and E2 production in rGCs. These results support the
      view that fenvalerate is considered as a kind of endocrine-disrupting chemicals.
      The mechanism of its disruption may involve the effects on steroidogenesis
      signaling cascades and/or steroidogenic enzyme's activity.

PMID- 16001831
TI  - Assessment of human DNA repair (NER) capacity with DNA repair rate (DRR) by comet
      assay.
AB  - OBJECTIVE: Alkaline comet assay was used to evaluate DNA repair (nucleotide
      excision repair, NER) capacity of human fresh lymphocytes from 12 young healthy
      non-smokers (6 males and 6 females). METHODS: Lymphocytes were exposed to UV-C
      (254 nm) at the dose rate of 1.5 J/m2/sec. Novobiocin (NOV) and aphidicolin
      (APC), DNA repair inhibitors, were utilized to imitate the deficiency of DNA
      repair capacity at the incision and ligation steps of NER. Lymphocytes from each
      donor were divided into three grougs: UVC group, UVC plus NOV group, and UVC plus
      APC group. DNA single strand breaks were detected in UVC irradiated cells
      incubated for 0, 30, 60, 90, 120, 180, and 240 min after UVC irradiation. DNA
      repair rate (DRR) served as an indicator of DNA repair capacity. RESULTS: The
      results indicated that the maximum DNA damage (i.e. maximum tail length) in the
      UVC group mainly appeared at 90 min. The ranges of DRRs in the UVC group were
      62.84%-98.71%. Average DRR value was 81.84%. The DRR difference between males and
      females was not significant (P < 0.05). However, the average DRR value in the UVC
      plus NOV group and the UVC plus APC group was 52.98% and 39.57% respectively,
      which were significantly lower than that in the UVC group (P < 0.01). CONCLUSION:
      The comet assay is a rapid, simple and sensitive screening test to assess
      individual DNA repair (NER) capacity. It is suggested that the time to detect DNA
      single strand breaks in comet assay should include 0 (before UV irradiation), 90
      and 240 min after exposure to 1.5 J x m(-2) UVC at least. The DRR, as an
      indicator, can represent the individual DNA repair capacity in comet assay.

PMID- 16001832
TI  - Comparison of susceptibilities of M. tuberculosis H37Ra and M. chelonei subsp.
      abscessus to disinfectants.
AB  - OBJECTIVE: To determine the susceptibilities of M. tuberculosis H37Ra and M.
      chelonei subsp. absecessus to several frequently-used disinfectants and to
      evaluate the practicability of surrogating M. tuberculosis by the latter.
      METHODS: A suspension quantitative bactericidal test was set up in accordance
      with Chinese Technique Standard for Disinfection to evaluate the susceptibility
      of each mycobacteria strain to each selected disinfectant. Killing log value was
      used as criterion in comparing the susceptibility to disinfectants between the
      two strains. RESULTS: M. chelonei subsp. abscessus was more resistant to chlorine
      disinfectant than M. tuberculosis while the two strains were similarly resistant
      to iodophor disinfectant, peracetic acid, alcohol and glutaraldehyde
      disinfectant. CONCLUSION: M. chelonei subsp. abscessus has the potential to
      surrogate M. tuberculosis in evaluating mycobactericidal efficacies of
      disinfectants.

PMID- 16001833
TI  - Association of neutralization sensitivity of HIV-1 primary isolates with
      biological properties of isolates from HIV-1 infected Chinese individuals.
AB  - OBJECTIVE: Although HIV-1 infection is prevalent in many regions in China, it
      remains largely unknown on the biological characteristics of dominant circulating
      isolates. This study was designed to isolate the circulating viral strains from
      different prevalent regions and to characterize their biological properties and
      neutralization sensitivity. METHODS: Primary viruses were isolated from fresh
      PBMCs using the traditional co-culture method and their capacity of inducing
      syncytium was tested in MT-2 cells. Meanwhile, their coreceptor usage was
      determined with two cell lines: Magi and GHOST (3) stably expressing CD4 and the
      chemokine receptor CCR5 or CXCR4. Furthermore, the sensitivity of these viruses
      to neutralization by HIV-1-infected patients' plasma which were highly active to
      neutralize SF33 strain, was quantified in GHOST cell-based neutralization assay.
      RESULTS: Six primary viral strains were isolated from 4 separated regions.
      Isolates LTG0213, LTG0214 and XVS032691 induced syncytia in MT-2 cells, and used
      CXCR4 as coreceptor. Isolates XJN0021, XJN0091, or SHXDC0041 did not induce
      syncytia, and used CCR5 as coreceptor. Overall neutralization sensitivity
      differed among four representative strains: HIV-1 XVS032691 > LTG0214 >XJN0091
      approximately SHXDC0041. CONCLUSION: The neutralization sensitivity of HIV
      isolates is linked with the phenotype of isolates, in which syncytium-inducing
      (SI) or CXCR4-tropic (X4) viruses are more easily neutralized than non-syncytium
      inducing (NSI) or CCR5-tropic (R5) viruses. The genetic subtypes based on the
      phylogeny of env sequences are not classical neutralization serotypes.

PMID- 16001834
TI  - Factors affecting bacterial growth in drinking water distribution system.
AB  - OBJECTIVE: To define the influence of some parameters, including assimilable
      organic carbon (AOC), chloramine residual, etc. on the bacterial growth in
      drinking water distribution systems. METHODS: Three typical water treatment
      plants in a northern city (City T) of China and their corresponding distribution
      systems were investigated. Some parameters of the water samples, such as
      heterotrophic plate content (HPC), AOC, COD(Mn), TOC, and phosphate were
      measured. RESULTS: The AOC in most water samples were more than 100 microg/L, or
      even more than 200 microg/L in some cases. The HPC in distribution systems
      increased significantly with the decrease of residual chlorine. When the residual
      chlorine was less than 0.1 mg/L, the magnitude order of HPC was 10(4) CFU/mL;
      when it was 0.5-0.7 mg/L, the HPC was about 500 CFU/mL. CONCLUSION: For
      controlling the biostability of drinking water, the controlling of AOC and
      residual chlorine should be considered simultaneously. The influence of phosphors
      on the AOC tests of water is not significant. Phosphors may not be the limiting
      nutrient in the water distribution systems.

PMID- 16001835
TI  - Pitchman for the gray revolution.

PMID- 16001836
TI  - Look out below! five threats to your financial security.

PMID- 16001837
TI  - UPLC: Ultra-performance liquid chromatography.

PMID- 16001838
TI  - Determination of methylbenzoquate in premixes and animal feeds using liquid
      chromatography with fluorescence detection.
AB  - A rapid analytical procedure was developed and tested for routine identification
      and quantification of methylbenzoquate in feeds by liquid chromatography (LC).
      The ground feed samples were extracted using methanol-water (80 + 20, v/v) at 65
      degrees-70 degrees C in a water bath for premixes and in dichloromethane at 45
      degrees C in a water bath for final feeds, respectively. The extract of final
      feeds was cleaned using solid-phase extraction on silica columns. Both the final
      feed and premix extracts were analyzed by reversed-phase LC on a NovaPak C18
      column (3.9 x 150 mm; 4 microm) with methanol-acetonitrile-water-phosphoric acid
      (340 + 350 + 308 + 2, v/v) as mobile phase. Fluorescence detection was performed
      at excitation and emission wavelengths of 265 and 390 nm, respectively.
      Alternatively, post-column addition of sulfuric acid solution was used to
      decrease the determination limit. The recovery of methylbenzoquate, in a
      concentration range of 0.5-10 mg/kg, was 105.0 +/- 7.3%. The limit of
      quantitation, based on a signal-to-noise ratio of 10:1, was 48 microg/kg. The
      developed LC method was tested in an interlaboratory study. The interlaboratory
      repeatibility for both samples ranged from 7.1 to 10.6%; the interlaboratory
      reproducibility ranged from 11.7 to 15.2%. With the post-column addition of
      sulfuric acid, the limit of quantification was decreased by a factor of 50.
      Overall, the developed method is highly selective and can be used in routine
      analysis.

PMID- 16001839
TI  - Determination of penicillin G in feeds by liquid chromatography with solid-phase
      extraction.
AB  - A liquid chromatographic method was developed for the determination of penicillin
      G in feeds. The method involves extraction of penicillin G with methanol,
      concentration under a stream of nitrogen, and cleanup using Phenomenex Strata-X
      solid-phase extraction cartridge. Analyte separation and quantification were
      achieved by gradient reversed-phase liquid chromatography and ultraviolet
      absorbance at 230 nm. Average spike recoveries for samples prepared at 3 spiking
      levels (25, 50, and 200 g/ton) were 96.3, 92.1, and 88.6%, respectively. The
      overall method precision at each of the 3 spiking levels was < or = 5.39%
      relative standard deviation. The limits of detection and quantititation (g/ton
      formulation) were 3.89 and 13.0 g/ton, respectively.

PMID- 16001840
TI  - Quantitative colorimetric analysis of aloe polysaccharides as a measure of Aloe
      vera quality in commercial products.
AB  - Aloe vera inner leaf gel has been used as a medicinal remedy for many years. Yet
      some aloe products do not demonstrate beneficial effects, indicating that poor
      quality products are reaching the market. Therefore, an efficient and accurate
      method is needed to evaluate the quality of aloe products. This paper describes a
      quick, quantitative colorimetric assay that has been developed for the
      determination of glucomannan in aloe gel and products. With this method,
      interference by non-aloe polysaccharides or other extraneous components was
      absent or negligible. Data indicate that the glucomannan can be determined at
      parts per million (mg/L) in aqueous solutions with an accuracy of 100 +/- 5% at a
      10 mg/L concentration. The correlation coefficient is 0.999, and linearity is
      from 0.9 to 72.7 mg/L in the test solution. The method is inexpensive, simple,
      sensitive, and reproducible. This method was applied to determine the
      polysaccharide content of commercial aloe products. Both qualitative and
      quantitative information can be obtained in about 5 min.

PMID- 16001841
TI  - Determination of flavonol aglycones in Ginkgo biloba dietary supplement crude
      materials and finished products by high-performance liquid chromatography: single
      laboratory validation.
AB  - A single laboratory validation (SLV) was completed for a method to determine the
      flavonol aglycones quercetin, kaempferol, and isorhamnetin in Ginkgo biloba
      products. The method calculates total glycosides based on these aglycones formed
      following acid hydrolysis. Nine matrixes were chosen for the study, including
      crude leaf material, standardized dry powder extract, single and multiple entity
      finished products, and ethanol and glycerol tinctures. For the 9 matrixes
      evaluated as part of this SLV, the method appeared to be selective and specific,
      with no observed interferences. The simplified 60 min oven heating hydrolysis
      procedure was effective for each of the matrixes studied, with no apparent or
      consistent differences between 60, 75, and 90 min at 90 degrees C. A Youden
      ruggedness trial testing 7 factors with the potential to affect quantitative
      results showed that 2 factors (volume hydrolyzed and test sample
      extraction/hydrolysis weight) were the most important parameters for control
      during sample preparation. The method performed well in terms of precision, with
      4 matrixes tested in triplicate over a 3-day period showing an overall
      repeatability (relative standard deviation, RSD) of 2.3%. Analysis of variance
      testing at alpha = 0.05 showed no significant differences among the within- or
      between-group sources of variation, although comparisons of within-day (Sw),
      between-day (Sb), and total (St) precision showed that a majority of the standard
      deviation came from within-day determinations for all matrixes. Accuracy testing
      at 2 levels (approximately 30 and 90% of the determined concentrations in
      standardized dry powder extract) from 2 complex negative control matrixes showed
      an overall 96% recovery and RSD of 1.0% for the high spike, and 94% recovery and
      RSD of 2.5% for the low spike. HorRat scores were within the limits for
      performance acceptability, ranging from 0.4 to 1.3. Based on the performance
      results presented herein, it is recommended that this method progress to the
      collaborative laboratory trial.

PMID- 16001842
TI  - Rapid and easy identification of Illicium verum Hook. f. and its adulterant
      Illicium anisatum Linn. by fluorescent microscopy and gas chromatography.
AB  - Illicium verum Hook. f. is used as an herbal tea to treat colic pain in infants.
      Reports suggest that Star anise herbal tea may be adulterated with Illicium
      anisatum Linn. A short and rapid method using microscopy and gas chromatography
      (GC) was developed to detect I. anisatum Linn., an adulterant in the powdered
      mixture of I. verum. Anatomical differences in the epicarp cells of I. verum and
      I. anisatum fruits were clearly defined as examined under fluorescent microscopy
      and scanning electron microscopy. A GC method was developed for quick
      identification of possible I. anisatum adulteration with I. verum.

PMID- 16001843
TI  - Macroscopic and microscopic authentication of Chinese and North American species
      of Ephedra.
AB  - Ephedra sinica Stapf or Ma Huang has been used in traditional Chinese medicine
      for over 5000 years as a bronchodilating and stimulatory agent. In the West, it
      is popularly used in dietary supplements for weight loss and to enhance athletic
      performance. Adverse events have been reported following consumption of dietary
      supplements containing ephedrine alkaloids. There are about 50 known species of
      Ephedra. The ratio of ephedrine to other alkaloids varies from species to
      species; all North American species lack alkaloids. The method commonly used in
      the dietary supplement industry for botanical authentication is to analyze the
      product for the presence of chemical markers known to be present in the specific
      herb. However, this method does not ensure that the product contains authentic
      herb, especially if it has been spiked with chemical marker compounds. In the
      trade and raw drug market, Ephedra is available in the form of stem cuttings or
      powders, without any vouchers, thus making identification of the species
      difficult. Using light microscopy, we can detect the presence of Ephedra herb,
      even in powder form, and identify within certain limits its geographical origin.
      Identification of Chinese and North American species of Ephedra has been made
      easier by developing a key using leaf and internode length as key identification
      characters.

PMID- 16001844
TI  - Determination of "net carbohydrates" using high-performance anion exchange
      chromatography.
AB  - For labeling purposes, the carbohydrate content of foods has traditionally been
      determined by difference. This value includes sugars, starches, fiber, dextrins,
      sugar alcohols, polydextrose, and various other organic compounds. In some cases,
      the current method may lack sufficient specificity, precision, and accuracy.
      These are subsequently quantitated by high performance anion exchange
      chromatography with pulsed amperometric detection and expressed as total nonfiber
      saccharides or percent "net carbohydrates." In this research, a new method was
      developed to address this need. The method consists of enzyme digestions to
      convert starches, dextrins, sugars, and polysaccharides to their respective
      monosaccharide components. These are subsequently quantified by high-performance
      anion exchange chromatography with pulsed amperometric detector and expressed as
      total nonfiber saccharides or percent "net carbohydrates." Hydrolyzed end
      products of various novel fibers and similar carbohydrates have been evaluated to
      ensure that they do not register as false positives in the new test method. The
      data generated using the "net carbohydrate" method were, in many cases,
      significantly different than the values produced using the traditional
      methodology. The recoveries obtained in a fortified drink matrix ranged from 94.9
      to 105%. The coefficient of variation was 3.3%.

PMID- 16001845
TI  - Development of methods for determination of the residues of 15 pesticides in
      medicinal herbs Isatis indigotica Fort. by capillary gas chromatography with
      electron capture or flame photometric detection.
AB  - Two multiresidue methods were developed for the determination of 15 pesticides
      (organochlorines, organphosphorus compounds, pyrethroids, and fungicides) in
      medicinal herbs Isatis indigotica Fort. and its formulations. The analytical
      procedure is based on ultrasonic assisted extraction and liquid-liquid extraction
      (LLE). After solvents were added, the raw material or granule sample was
      sonicated in an ultrasonic water bath and then centrifuged, filtered, and cleaned
      up by LLE. The infusion sample was extracted with petroleum ether by LLE. The
      pesticide residues were determined by capillary gas chromatography with electron
      capture or flame photometric detection. Recoveries with the method at
      concentrations between 0.4 microg/kg and 10 mg/kg ranged from 70.2 to 119.5% for
      raw material, 73.2 to 105.1% for granule formulation, and 72.8 to 113.3% for
      infusion formulation. The relative standard deviation values were <20% for all of
      the pesticides studied. The pesticide detection limits were within the ranges 0.3
      0.5 microg/L for endosulfan, 3-7.5 microg/L for pyrethroids, 0.7-32.5 microg/L
      for organophosphorus pesticides, and 0.1-0.6 microg/L for the other pesticides.
      The proposed methods are simple and rapid and provide simultaneous determination
      of pesticide residues in Isatis indigotica Fort. with acceptable recoveries and
      repeatability and an adequate limit of determination.

PMID- 16001846
TI  - Multiresidue determination of organophosphorus pesticides in ginkgo leaves by
      accelerated solvent extraction and gas chromatography with flame photometric
      detection.
AB  - A rapid and simple method using accelerated solvent extraction and solid-phase
      extraction cleanup was developed and validated for the determination of 15
      organophosphorus pesticides in ginkgo leaves by capillary gas chromatography with
      flame photometric detection. The pesticides were extracted at 100 degrees C under
      1500 psi pressure in <20 min. The average recovery from 10 g ginkgo leaves,
      fortified at 3 levels ranging from 0.05 to 1.00 mg/kg, was 95.2% with a relative
      standard deviation of 4.6%. The limits of detection ranged from 1.11 x 10(-3)
      mg/kg (dimethoate) to 4.44 x 10(-3) mg/kg (dichlorvos). The proposed method
      showed acceptable accuracy and precision while minimizing environmental concerns,
      time, and labor. Furthermore, the method could be easily applied to the
      monitoring of these 15 organophosphorus pesticides in ginkgo leaves.

PMID- 16001847
TI  - Confirmation of sulfamethazine, sulfathiazole, and sulfadimethoxine residues in
      condensed milk and soft-cheese products by liquid chromatography/tandem mass
      spectrometry.
AB  - A liquid chromatography/tandem mass spectrometry method (LC/MS/MS) is described
      for the simultaneous detection of 3 sulfonamide drug residues at 1.25 ppb in
      condensed milk and soft-cheese products. The 3 sulfonamide drugs of interest are
      sulfathiazole (STZ), sulfamethazine (SMZ), and sulfadimethoxine (SDM). The method
      includes extraction of the product with phosphate buffer, centrifugation of the
      diluted product, and application of a portion of the extract onto a polymeric
      solid-phase extraction cartridge. The cartridge is washed with water, and the
      sulfonamides are eluted with methanol. After evaporation, the residue is
      dissolved in 0.1% formic acid solution, and the solution is filtered before
      analysis by LC/MS/MS. The LC/MS/MS program involved a series of time-scheduled
      selected-reaction monitoring transitions. The transitions of MH+ to the common
      product ions at m/z 156, 108, and 92 were monitored for each residue. In
      addition, SMZ and SDM had a fourth significant and unique product ion transition
      that could be measured. Validation was performed with control and fortified
      control condensed bovine milk with 2.5, 5, and 10 ppb sulfonamides. This method
      was applied to imported flavored and unflavored condensed milk and cream cheese
      bars. The presence of STZ and SMZ residues was confirmed in 3 out of 6 products.

PMID- 16001848
TI  - Determination of malachite green and leucomalachite green in a variety of
      aquacultured products by liquid chromatography with tandem mass spectrometry
      detection.
AB  - A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed
      for determining the residues of malachite green (MG) and leucomalachite green
      (LMG) in a number of aquatic species. MG and its metabolite were extracted from
      homogenized tissues with a perchloric acid-acetonitrile solution; the extract was
      centrifuged; and an aliquot was taken, concentrated, and passed through a
      chemically bonded octadecyl C18 solid-phase extraction column. The compounds of
      interest were eluted with acetonitrile, and the eluate was evaporated to dryness.
      The residue was dissolved in acetonitrile and diluted with water in preparation
      for analysis by LC/MS/MS. MG and its metabolite were determined by reversed-phase
      LC using a Luna C18 column with an ammonium hydroxide-formic acid buffer in
      acetonitrile gradient and MS/MS detection using multiple reaction monitoring.
      Calibration curves were linear for all analyses between 5 and 500 pg injected for
      both analytes, with recoveries ranging from 81% for LMG to 98% for MG in salmon
      spiked at the 1 ng/g level. Detection limits of 0.1 ng/g for both MG and LMG were
      easily obtainable using the recommended method. The operational errors,
      interferences, and recoveries for spiked samples compared favorably with those
      obtained by established methodology. The recommended method is simple, rapid, and
      specific for monitoring residues of MG and LMG in a number of aquatic species.

PMID- 16001849
TI  - Evaluation of the VIDAS Listeria (LIS) immunoassay for the detection of Listeria
      in foods using demi-Fraser and Fraser enrichment broths, as modification of AOAC
      Official Method 999.06 (AOAC Official Method 2004.06).
AB  - A multilaboratory study was conducted to compare the VIDAS LIS immunoassay with
      the standard cultural methods for the detection of Listeria in foods using an
      enrichment modification of AOAC Official Method 999.06. The modified enrichment
      protocol was implemented to harmonize the VIDAS LIS assay with the VIDAS LMO2
      assay. Five food types--brie cheese, vanilla ice cream, frozen green beans,
      frozen raw tilapia fish, and cooked roast beef--at 3 inoculation levels, were
      analyzed by each method. A total of 15 laboratories representing government and
      industry participated. In this study, 1206 test portions were tested, of which
      1170 were used in the statistical analysis. There were 433 positive by the VIDAS
      LIS assay and 396 positive by the standard culture methods. A Chi-square analysis
      of each of the 5 food types, at the 3 inoculation levels tested, was performed.
      The resulting average Chi square analysis, 0.42, indicated that, overall, there
      are no statistical differences between the VIDAS LIS assay and the standard
      methods at the 5% level of significance.

PMID- 16001850
TI  - Multiresidue method for determination of algal toxins in shellfish: single
      laboratory validation and interlaboratory study.
AB  - A method that uses liquid chromatography with tandem mass spectrometry (LC/MS/MS)
      has been developed for the highly sensitive and specific determination of amnesic
      shellfish poisoning toxins, diarrhetic shellfish poisoning toxins, and other
      lipophilic algal toxins and metabolites in shellfish. The method was subjected to
      a full single-laboratory validation and a limited interlaboratory study. Tissue
      homogenates are blended with methanol-water (9 + 1), and the centrifuged extract
      is cleaned up with a hexane wash. LC/MS/MS (triple quadrupole) is used for
      quantitative analysis with reversed-phase gradient elution (acidic buffer),
      electrospray ionization (positive and negative ion switching), and multiple
      reaction monitoring. Ester forms of dinophysis toxins are detected as the parent
      toxins after hydrolysis of the methanolic extract. The method is quantitative for
      6 key toxins when reference standards are available: azaspiracid-1 (AZA1), domoic
      acid (DA), gymnodimine (GYM), okadaic acid (OA), pectenotoxin-2 (PTX2), and
      yessotoxin (YTX). Relative response factors are used to estimate the
      concentrations of other toxins: azaspiracid-2 and -3 (AZA2 and AZA3), dinophysis
      toxin-1 and -2 (DTX1 and DTX2), other pectenotoxins (PTX1, PTX6, and PTX11),
      pectenotoxin secoacid metabolites (PTX2-SA and PTX11-SA) and their 7-epimers,
      spirolides, and homoYTX and YTX metabolites (45-OHYTX and carboxyYTX). Validation
      data have been gathered for Greenshell mussel, Pacific oyster, cockle, and
      scallop roe via fortification and natural contamination. For the 6 key toxins at
      fortification levels of 0.05-0.20 mg/kg, recoveries were 71-99% and single
      laboratory reproducibilities, relative standard deviations (RSDs), were 10-24%.
      Limits of detection were <0.02 mg/kg. Extractability data were also obtained for
      several toxins by using successive extractions of naturally contaminated mussel
      samples. A preliminary interlaboratory study was conducted with a set of toxin
      standards and 4 mussel extracts. The data sets from 8 laboratories for the 6 key
      toxins plus DTX1 and DTX2 gave within-laboratories repeatability (RSD(R)) of 8
      12%, except for PTX-2. Between-laboratories reproducibility (RSDR) values were
      compared with the Horwitz criterion and ranged from good to adequate for 7 key
      toxins (HorRat values of 0.8-2.0).

PMID- 16001851
TI  - Determination of ochratoxin A in green coffee by immunoaffinity column cleanup
      and liquid chomatography: collaborative study.
AB  - A collaborative study was conducted to evaluate a method using immunoaffinity
      column cleanup with liquid chromatography (LC) for the determination of
      ochratoxin A (OTA) in green coffee at levels that could be included in possible
      future regulations of the European Union. The test portion was extracted with
      methanol-3% aqueous sodium hydrogen carbonate solution (50 + 50, v/v). The
      extract was filtered, and the filtrate was diluted with phosphate-buffered saline
      and applied to an immunoaffinity column containing antibodies specific for OTA.
      After washing, the toxin was eluted from the column with methanol and quantified
      by LC with fluorescence detection. Pairs of 4 homogeneous noncontaminated and
      naturally contaminated materials (mean levels of < 0.12, 2.44, 5.15, and 13.46
      ng/g) and blank samples (< 0.12 ng/g) for spiking were sent to 20 participant
      laboratories from 8 countries. The materials were analyzed according to the
      method description and all difficulties encountered in the analysis were
      reported. Statistical analysis was carried out according to the Harmonized
      Protocol of the International Union of Pure and Applied Chemistry. The relative
      standard deviation for repeatability (RSDr) ranged from 7.42 to 20.94%, and the
      relative standard deviation for reproducibility (RSDR) ranged from 16.34 to
      29.17%. The method showed acceptable within-laboratory and between-laboratories
      precision for green coffee materials, as evidenced by HorRat values of < or =
      0.85, at the studied range, for spiked and naturally contaminated materials. The
      mean recovery was 92.8% for green coffee material spiked with OTA at a level of
      4.82 ng/g.

PMID- 16001852
TI  - Testing green coffee for ochratoxin A, part II: Observed distribution of
      ochratoxin A test results.
AB  - The suitability of 4 theoretical distributions (normal, lognormal, negative
      binomial, and gamma) to predict the observed distribution of ochratoxin A (OTA)
      in green coffee was investigated. One symmetrical and 3 positively skewed
      theoretical distributions were each fitted to 25 empirical distributions of OTA
      test results for green coffee beans. Parameters of each theoretical distribution
      were calculated by using Methods of Moments. The 3 skewed theoretical
      distributions provided acceptable fits to each of the 25 observed distributions.
      Because of its simplicity, the lognormal distribution was selected to model OTA
      test results for green coffee. Using variance equations determined in previous
      studies, mathematical expressions were developed to calculate the parameters of
      the log normal distribution for a given OTA lot concentration and test procedure.
      Observed acceptance probabilities were compared to an operating characteristic
      curve predicted from the lognormal distribution, and all 25 observed acceptance
      probabilities were found to lie within the 95% confidence band associated with
      the predicted operating characteristic curve. The parameters of compound gamma
      distribution were used to calculate the fraction of OTA contamination beans
      within a contaminated lot. The percent-contaminated beans were a function of the
      lot concentration and increased with lot concentration. At a lot concentration of
      5 microg/kg, approximately 6 beans per 10,000 beans are contaminated.

PMID- 16001853
TI  - A square-wave adsorptive stripping voltammetric method for the determination of
      Amaranth, a food additive dye.
AB  - Square-wave adsorptive stripping voltammetric (AdSV) determinations of trace
      concentrations of the azo coloring agent Amaranth are described. The analytical
      methodology used was based on the adsorptive preconcentration of the dye on the
      hanging mercury drop electrode, followed by initiation of a negative sweep. In a
      pH 10 carbonate supporting electrolyte, Amaranth gave a well-defined and
      sensitive AdSV peak at -518 mV. The electroanalytical determination of this azo
      dye was found to be optimal in carbonate buffer (pH 10) under the following
      experimental conditions: accumulation time, 120 s; accumulation potential, 0.0 V;
      scan rate, 600 mV/s; pulse amplitude, 90 mV; and frequency, 50 Hz. Under these
      optimized conditions the AdSV peak current was proportional over the
      concentration range 1 x 10(-8)-1.1 x 10(-7) mol/L (r = 0.999) with a detection
      limit of 1.7 x 10(-9) mol/L (1.03 ppb). This analytical approach possessed
      enhanced sensitivity, compared with conventional liquid chromatography or
      spectrophotometry and it was simple and fast. The precision of the method,
      expressed as the relative standard deviation, was 0.23%, whereas the accuracy,
      expressed as the mean recovery, was 104%. Possible interferences by several
      substances usually present as food additive azo dyes (E110, E102), gelatin,
      natural and artificial sweeteners, preservatives, and antioxidants were also
      investigated. The developed electroanalyticals method was applied to the
      determination of Amaranth in soft drink samples, and the results were compared
      with those obtained by a reference spectrophotometric method. Statistical
      analysis (paired t-test) of these data showed that the results of the 2 methods
      compared favorably.

PMID- 16001854
TI  - The use of electrodialysis to prepare aqueous bread extracts for bromate
      determination by chemiluminescence.
AB  - A cleanup procedure based on electrodialysis is described for the preparation of
      aqueous bread extracts for bromate determination by chemiluminescence. The
      technique utilizes electrophoresis with 3 chambers separated by semipermeable
      membranes. The relative merits of reverse osmosis (RO), ultrafiltration, and
      nanofiltration membranes with various molecular weight cutoffs were evaluated.
      The best results were obtained with an RO membrane manufactured from thin-film
      (composite) polysulfone as support for polyamide. A 0.14 M sodium sulfate
      solution in the center or collection chamber provides optimum conductivity.
      Aqueous hydroxylamine sulfate (30 mM) was selected for the anode compartment as a
      reductant for the anode oxidation products. The constant current mode at 150 mA
      with a potential of ca 100 volts was used. After electrophoretic separation, the
      bromate concentration in the collection chamber was typically 2 to 3 times
      greater than the concentration in the bread extract. The chemiluminescent
      reaction of bromate with sulfite with hydrocortisone as the enhancer was selected
      for detection of bromate. The emission, with a wavelength maximum at 575 nm, was
      found to "glow" rather than "flash" after the reagents were mixed; therefore, it
      was possible to optimize the light collection period. The method was validated
      with a variety of commercial bread products. White bread, hot dog buns, hamburger
      rolls, and a multigrain bread from 7 different manufacturers were studied.

PMID- 16001855
TI  - Precise method for the measurement of catalase activity in honey.
AB  - An improved method is reported for the determination of catalase activity in
      honey. We tested different dialysis membranes, dialysis fluid compositions and
      amounts, dialysis temperatures, sample amounts, and dialysis times. The best
      results were obtained by dialysis of 7.50 g sample in a cellulose dialysis sack,
      using two 3 L portions of 0.015 M sodium phosphate buffer (pH 7.0) as the
      dialysis fluid at 4 degrees C for 22 h. As in previous methods, catalase activity
      was determined on the basis of the rate of disappearance of the substrate, H202,
      with the H202 determined spectrophotometrically at 400 nm in an assay system
      containing o-dianisidine and peroxidase. Trials indicated that the best solvent
      for the o-dianisidine was 0.2 M sodium phosphate buffer, pH 6.1; the best
      starting H202 concentration was 3 mM; the best HCl concentration for stopping the
      reaction was 6 N; and the best sample volume for catalase measurement was 7.0 mL.
      Precision values (relative standard deviations for analyses of 10 subsamples of
      each of 3 samples) were high, ranging from 0.48% for samples with high catalase
      activity to 1.98% for samples with low catalase activity.

PMID- 16001856
TI  - Comparison of total folate concentrations in foods determined by microbiological
      assay at several experienced U.S. commercial laboratories.
AB  - Analysis of total folate concentration measured by microbiological assay in a
      variety of foods submitted in a routine manner to experienced laboratories that
      regularly perform folate analysis on fee-for-service basis was evaluated.
      Homogenates of fresh strawberries, frozen spinach, orange juice, frozen meat and
      vegetable pizza, dry macaroni, and dried pinto beans were prepared and stored
      under conditions previously determined to maintain stability of folate content.
      An aliquot of each composite and of 3 certified reference materials were sent on
      each of 4 occasions to 4 laboratories. Results for macaroni and pizza, the only
      folic acid-fortified foods, had considerably lower between-laboratory variation
      (CV(B)) with CV(B) of 9-11% versus >45% for other foods. Mean total folate ranged
      from 14 to 279 microg/100 g for a mixed vegetable reference material, from 5 to
      70 microg/100 g for strawberries, and from 28 to 81 microg/100 g for wholemeal
      flour. Only 1 laboratory reported using a tri-enzyme extraction, and all
      laboratories used folic acid fortified foods as internal control materials. Users
      of commercial total folate analysis should understand the uncertainty in values
      determined by microbiological assay, particularly for foods containing primarily
      naturally occurring folate, which may not be apparent when replicate samples are
      not submitted for analysis.

PMID- 16001857
TI  - Real-time polymerase chain reaction detection of cauliflower mosaic virus to
      complement the 35S screening assay for genetically modified organisms.
AB  - Labeling of genetically modified organisms (GMOs) is now in place in many
      countries, including the European Union, in order to guarantee the consumer's
      choice between GM and non-GM products. Screening of samples is performed by
      polymerase chain reaction (PCR) amplification of regulatory sequences frequently
      introduced into genetically modified plants. Primers for the 35S promoter from
      Cauliflower mosaic virus (CaMV) are those most frequently used. In virus-infected
      plants or in samples contaminated with plant material carrying the virus, false
      positive results can consequently occur. A system for real-time PCR using a
      TaqMan minor groove binder probe was designed that allows recognition of virus
      coat protein in the sample, thus allowing differentiation between transgenic and
      virus-infected samples. We measured the efficiency of PCR amplification, limits
      of detection and quantification, range of linearity, and repeatability of the
      assay in order to assess the applicability of the assay for routine analysis. The
      specificity of the detection system was tested on various virus isolates and
      plant species. All 8 CaMV isolates were successfully amplified using the designed
      system. No cross-reactivity was detected with DNA from 3 isolates of the closely
      related Carnation etched ring virus. Primers do not amplify plant DNA from
      available genetically modified maize and soybean lines or from different species
      of Brassicaceae or Solanaceae that are natural hosts for CaMV. We evaluated the
      assay for different food matrixes by spiking CaMV DNA into DNA from food samples
      and have successfully amplified CaMV from all samples. The assay was tested on
      rapeseed samples from routine GMO testing that were positive in the 35S screening
      assay, and the presence of the virus was confirmed.

PMID- 16001858
TI  - Safety evaluation of single-use medical devices after submission to simulated
      reutilization cycles.
AB  - Pyrogenic and toxic reactions, especially in immunologically compromised
      patients, are among the risks associated with reuse of single-use medical devices
      (SUDs) with recurrent damaged surfaces. These drawbacks have raised serious
      doubts about the true benefits of the reprocessing practice. Taking into
      consideration prolonged patients' stay in hospitals due to adverse reactions
      provoked by recycled SUDs, the safety of these reprocessed materials was
      evaluated. The reprocessing cycles were simulated after intentional contamination
      of selected test material such as intravenous catheters, 3-way stopcocks, and
      tracheostomy tubes with Bacillus subtilis var. niger ATCC 9372 spores (10(7)
      CFU/unit). The repeated reprocessing cycles consisted of subsequent wash with
      enzymatic detergent followed by drying and sterilization with ethylene oxide-CFC
      (12 + 88), 600 mg/L at 55 degrees C, relative humidity 60%, for 3 h. After each
      reprocessing cycle, specimen samples were evaluated by pour plate microbial
      counts, direct and indirect inoculation sterility tests, cytotoxicity evaluation,
      and scanning electron microscopy (SEM). Microbial counts as high as 10(3) CFU
      were evident even after the 10th reprocessing cycle, besides scratched and
      damaged surfaces observed by SEM. Risk-benefit viewpoints are discussed.

PMID- 16001859
TI  - Experimental evaluation of different precision criteria applicable to
      microbiological counting methods.
AB  - The dispersion of microbiological counting measurements, when repeating the
      analysis on the same material both within a laboratory (repeatability) and
      between laboratories (reproducibility) can be characterized by the organization
      of interlaboratory studies, where several sets of identical test materials are
      sent to several laboratories. Using the example of data generated by an
      interlaboratory study on enumeration of Listeria monocytogenes in foods by the
      standardized reference method (colony-count technique), 2 types of robust
      estimators of reproducibility standard deviations, based on the median, were
      examined, in comparison with the classical estimators, based on the mean.
      Experimental evaluation indicated that the 3 approaches gave consistent results
      for most of the combinations. The usual log10 transformation of the enumeration
      results was also questioned before these calculations were conducted.

PMID- 16001860
TI  - Flame atomic absorption spectrometric determination of trace amounts of nickel
      after extraction and preconcentration onto natural modified analcime zeolite
      loaded with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol.
AB  - Nickel is a moderately toxic element compared with other transition metals.
      However, inhalation of nickel and its compounds leads to serious problems,
      including cancer of the respiratory system and a skin disorder, nickel-eczema.
      Thus, attention has focused on the toxicity of nickel at low concentrations, and
      the development of reliable, analytical approaches for the determination of trace
      amounts of nickel is needed. This paper describes a simple, rapid, and sensitive
      flame atomic absorption spectrometric method for the determination of trace
      amounts of nickel in various samples after adsorption of its 2-(5-bromo-2
      pyridylazo)-5-diethylaminophenol complex on a modified Analcime column in the pH
      range of 7.5-10.5. The retained analyte on the Analcime is recovered with 5.0 mL
      2 M nitric acid and determined by flame atomic absorption spectrometry. The
      detection limit is 20 ng/mL, and the calibration curve is linear for analyte
      concentrations in the range of 0.1-8 microg/mL final solution, with a correlation
      coefficient of 0.9993. Eight replicate determinations of nickel at 2 microg/mL in
      the final solution gave an absorbance of 0.1222, with a relative standard
      deviation (RSD) of +/-1.2%. The interference of a large number of anions and
      cations was studied, and the proposed method was used for the determination of
      nickel in various standard reference samples. The accuracy of the proposed method
      was evaluated by analyzing standard reference samples, and the results were
      satisfactory (recoveries of >96%; RSD of <3.5%).

PMID- 16001861
TI  - Screening and evaluation of fruit samples for four pesticide residues.
AB  - The occurrence of 4 pesticide residues, imidacloprid, carbendazim, methiocarb,
      and hexythiazox, was assessed in several fruits (oranges, tangerines,
      watermelons, and date plums) from the Valencian Community (Spain). A total of 227
      samples--56 oranges, 134 tangerines, 13 watermelons, and 24 date plums--were
      taken from an agricultural cooperative representative of the area studied during
      2001. The pesticides were determined by liquid chromatography/mass spectrometry
      after sample extraction with ethyl acetate and anhydrous sodium sulfate.
      Recoveries of 4 pesticides at 2 fortification levels (0.02 and 0.2 mg/kg), the
      lower of which was the quantification limit, ranged from 60 to 108%.
      Concentrations of imidacloprid, carbendazim, methiocarb, and hexythiazox ranged
      from 0.02 to 0.75 mg/kg in 184 samples (54 oranges, 119 tangerines, 3
      watermelons, and 8 date plums). Nineteen samples contained methiocarb or
      hexythiazox residues that exceeded the maximum residue limits. Calculation of the
      estimated daily intakes of the 4 pesticides studied and their comparison with the
      Acceptable Daily Intakes established by the Food and Agriculture Organization of
      the World Health Organization demonstrated the safety of fruit consumption and
      showed the importance of monitoring for pesticide residues.

PMID- 16001862
TI  - Extraction of fipronil and thiobencarb from anaerobic water samples using solid
      phase extraction.
AB  - Anaerobic water samples containing levels of soluble Fe(II) may form insoluble
      Fe(III) particulates that could hinder subsequent extraction and analysis. Solid
      phase extraction (SPE) cartridges could become blocked by this material, reducing
      the volume that can be processed. The ability of ascorbic acid to reduce these
      Fe(III) colloids and/or to prevent further oxidation of Fe(II) by dissolved
      oxygen during sampling was investigated and compared to sample stabilization with
      hydrochloric acid. Ascorbic acid (5%, w/v) proved the most effective treatment
      because it prevented 95% of the dissolved iron in the sample from precipitating
      during processing, compared to 40% in untreated samples. The effect of ascorbic
      acid addition on degradation of 2 rice pesticides, fipronil and thiobencarb, was
      investigated and compared to degradation rates in water. Pesticide reduction by
      ascorbic acid over a 3 h period was insignificant compared to the natural
      degradation occurring in deionized water. While this method was shown to increase
      sample processing time, it also allowed the processing of large-volume anaerobic
      water samples (150 mL) that were previously not extractable due to rapid
      obstruction of the SPE cartridge.

PMID- 16001863
TI  - Flow-through fluorescence-based optosensor with on-line solid-phase separation
      for the simultaneous determination of a ternary pesticide mixture.
AB  - A rapid and selective method was developed for the simultaneous determination of
      3 widely used pesticides, carbendazim (CBZ), carbofuran (CF), and benomyl (BNM).
      The method utilized a single continuous-flow, solid surface fluorometric
      multioptosensor implemented with a previous separation of the analytes on a
      minicolumn, placed just before the sensor, that was packed with the same solid
      support (C18 silica gel) as the flow-through cell. The separation was achieved
      because of the different kinetics of retention/elution of the pesticides on the
      solid support in the minicolumn, enabling the sequential arrival of the analytes
      at the sensing zone. With a single injection of the mixture, 2 of them were more
      strongly retained in the minicolumn (CF and BNM) while the other (CBZ) passed
      through the system towards the sensing material where it developed its
      fluorescence transitory signal. Then, CF and BNM were successively eluted from
      the solid support using 2 different eluting solutions, and they sequentially
      reached the sensing zone and developed their respective signals. A
      multiwavelength fluorescence detection mode was used, recording the signals of
      each pesticide at its maximum excitation/emission wavelength; therefore, the
      sensitivity was increased. The system was calibrated using a sample volume of
      2000 microL. The linear dynamic range was 80-1400, 250-2400, and 150-2000 ng/mL
      with detection limits of 15, 68, and 35 ng/mL and relative standard deviation
      values of 3.5, 3.2, and 2.4% for CBZ, CF, and BNM, respectively. A recovery study
      was applied to spiked environmental water samples, and recoveries ranged from 96
      to 104%.

PMID- 16001864
TI  - Sensitive determination of anionic surfactants in water with trans-4-[4'-(N
      methyl-N-hydroxylethylamino)-cinnamyl-N-9-(4'-(2,2':6',2''-terpyridine))
      phenylmethylene]pyridine bromide by the light-absorption ratio variation
      approach.
AB  - The light-absorption ratio variation approach was described and applied to the
      determination of anionic surfactants (AS) in water with a novel chromophore,
      trans 4-[4'-(N-methyl-N-hydroxylethylamino)-cinnamyl-N-9-(4'-(2,2':6',2''
      terpyridine))-phenylmethylene]pyridine bromide (BTMHCTPP). The complexations
      between BTMHCTPP and sodium dodecyl sulfate (SDS) and sodium
      dodecylbenzenesulfonate (SDBS) at pH 3.85 were characterized by the break point
      approach. Results have shown that both 1BTMHCTPP:1SDS and 1BTMHCTPP:1SDBS
      complexes were formed, and that deltaA(r) (deltaA(r) = light-absorption ratio
      variation) is linear for the range of AS between 0.05 and 1.00 mg/L. The limits
      of detection (3sigma) are 0.045 mg/L for SDS and 0.040 mg/L for SDBS. The
      complexation is selective in the presence of EDTA, and it has been applied to the
      analysis of water samples with satisfactory results.

PMID- 16001865
TI  - Dietary protein quality in humans--an overview.
AB  - The first objective in evaluating protein quality is to permit a ranking of
      proteins according to their potential nutritive value and to permit detection of
      changes in nutritive value due to processing and/or storage. The second objective
      is to permit prediction of the contribution a food protein, or mixture of food
      proteins, makes toward meeting nitrogen and amino acid requirements for growth or
      maintenance. Different approaches are used in meeting these distinct aims. The
      preferred current method to meet the second aim is the protein digestibility
      corrected amino acid score (PDCAAS). This article introduces the concept of
      PDCAAS and places it in the context of the series of papers published in this
      Special Guest Editor Section addressing aspects of dietary amino acid
      utilization.

PMID- 16001866
TI  - Chromatographic determination of amino acids in foods.
AB  - Amino acids in foods exist in a free form or bound in peptides, proteins, or
      nonpeptide bonded polymers. Naturally occurring L-amino acids are required for
      protein synthesis and are precursors for essential molecules, such as co-enzymes
      and nucleic acids. Nonprotein amino acids may also occur in animal tissues as
      metabolic intermediates or have other important functions. The development of
      bacterially derived food proteins, genetically modified foods, and new methods of
      food processing; the production of amino acids for food fortification; and the
      introduction of new plant food sources have meant that protein amino acids and
      amino acid enantiomers in foods can have both nutritional and safety implications
      for humans. There is, therefore, a need for the rapid and accurate determination
      of amino acids in foods. Determination of the total amino acid content of foods
      requires protein hydrolysis by various means that must take into account
      variations in stability of individual amino acids and resistance of different
      peptide bonds to the hydrolysis procedures. Modern methods for separation and
      quantitation of free amino acids either before or after protein hydrolysis
      include ion exchange chromatography, high performance liquid chromatography (LC),
      gas chromatography, and capillary electrophoresis. Chemical derivatization of
      amino acids may be required to change them into forms amenable to separation by
      the various chromatographic methods or to create derivatives with properties,
      such as fluorescence, that improve their detection. Official methods for
      hydrolysis and analysis of amino acids in foods for nutritional purposes have
      been established. LC is currently the most widely used analytical technique,
      although there is a need for collaborative testing of methods available. Newer
      developments in chromatographic methodology and detector technology have reduced
      sample and reagent requirements and improved identification, resolution, and
      sensitivity of amino acid analyses of food samples.

PMID- 16001867
TI  - The effect of hydrolysis time on amino acid analysis.
AB  - Determining the amino acid content of a protein involves the hydrolysis of that
      protein, usually in acid, until the protein-bound amino acids are released and
      made available for detection. Both the variability in the ease of peptide bond
      cleavage and differences in the acid stability of certain amino acids can
      significantly affect determination of a protein's amino acid content. By using
      multiple hydrolysis intervals, a greater degree of accuracy can be obtained in
      amino acid analysis. Correction factors derived by linear extrapolation of serial
      hydrolysis data are currently used. Compartmental modeling of the simultaneous
      hydrolysis (yield) and degradation (decay) of amino acids by nonlinear multiple
      regression of serial hydrolysis data has also been validated and applied to
      determine the amino acid composition of various biological samples, including egg
      white lysozyme, human milk protein, and hair. Implicit in the routine application
      of serial hydrolysis in amino acid analysis, however, is an understanding that
      correction factors, derived either linearly or through the more accurate
      nonlinear multiple regression approach, need to be determined for individual
      proteins rather than be applied uniformly across all protein types.

PMID- 16001868
TI  - The absorption and metabolism of modified amino acids in processed foods.
AB  - The chemical reactions involved in the modifications of amino acids in processed
      food proteins are described. They concern the Maillard reaction, reaction with
      polyphenols and tannins, formation of lysinoalanine during alkaline and heat
      treatments, formation of isopeptides, oxidation reaction of the sulfur amino
      acids, and isomerization of the L-amino acids into their D-form. Information on
      the digestion, absorption, and urinary excretion of the reaction products
      obtained by using conventional nutritional tests is given. The studies that have
      been made on the metabolism of these molecules by using a radioisotopic approach
      to follow their kinetics in the organism after ingestion are also reviewed. This
      approach provides unique data on the quantitation of the metabolic pathways and
      on the kinetics of the metabolic processes involved.

PMID- 16001869
TI  - The impact of processing on the nutritional quality of food proteins.
AB  - During many food processing regimens, food proteins may undergo a variety of
      chemical modifications. Despite the enormous consumption of processed foods
      worldwide, much remains to be learned about the exact nature of these
      modifications. This is partly due to the complex nature of the changes involved,
      and partly to the problems of analysis imposed by the intractable nature of the
      food matrix. Such difficulties are compounded by the paucity of chemically based
      analytical tests that accurately measure amino acid availability in biologically
      relevant terms. In this review, we explore the known changes that proteins and
      amino acids undergo during food processing and the consequences of these changes
      on the physical and nutritional qualities of the food. We also examine the impact
      of these protein derivatizations for the analysis of food proteins and amino
      acids, and highlight areas that require future research.

PMID- 16001870
TI  - In vivo determination of amino acid bioavailability in humans and model animals.
AB  - Because the digestion of many dietary proteins is incomplete, and because there
      is a continuous (but variable) entry into the intestinal lumen of endogenous
      protein and amino acid nitrogen that is also subject to digestion, the fluxes of
      nitrogen, amino acids, and protein in the gut exhibit a rather complicated
      pattern. Methods to distinguish and quantitate the endogenous and dietary
      components of nitrogen and amino acids in ileal chyme or feces include the use of
      a protein-free diet, the enzyme-hydrolyzed protein method, different levels of
      protein intake, multiple regression methods, and stable-isotope labelling of
      endogenous or exogenous amino acids. Assessment of bioavailability can be made,
      with varying degrees of difficulty, in man directly but, for routine evaluation
      of foods, the use of model animals is attractive for several reasons, the main
      ones being cost and time. Various animals and birds have been proposed as models
      for man but, in determining their suitability as a model, their physiological,
      enzymological, and microbiological differences must be considered. Fecal or ileal
      digestibility measurements, as well as apparent and true nitrogen and amino acid
      digestibility measurements, have very different nutritional significance and can,
      thus, be used for different objectives. Measurements at the ileal level are
      critical for determining amino acid losses of both dietary and endogenous origin,
      whereas measurements at the fecal level are critical in assessing whole-body
      nitrogen losses. A complementary and still unresolved aspect is to take into
      account the recycling of intestinal nitrogen and bacterial amino acids to the
      body.

PMID- 16001871
TI  - In vitro determination of the release kinetics of peptides and free amino acids
      during the digestion of food proteins.
AB  - The kinetics of peptide release during in vitro digestion of 4 protein sources
      (casein, cod protein, soy protein, and gluten) were investigated. Samples were
      sequentially hydrolyzed with pepsin (30 min) and pancreatin (2, 4, or 6 h) in a
      dialysis cell with continuous removal of digestion products. Nondialyzed digests
      were fractionated by ion-exchange chromatography and ultrafiltration. Animal
      proteins were digested at a greater rate than plant proteins. Target amino acids
      of specific enzymes appeared more rapidly in the dialyzed fractions when compared
      to other amino acids. Throughout the hydrolysis, nondialyzed digests contained a
      higher proportion of peptide mixtures with basic-neutral properties. Except for
      gluten, peptide fractions with molecular weights that exceeded 10 kDa (basic
      neutral, BN > 10) were rapidly hydrolyzed during the first 2 h of pancreatin
      digestion. The kinetics of release and the composition of peptide fractions were
      different when the protein sources were compared. The analysis of amino acids
      revealed that threonine and proline proportions were relatively high in BN > 10
      and in peptide fractions with molecular weight between 10-1 kDa (BN 10-1), while
      tyrosine, phenylalanine, lysine, and arginine predominated in the low molecular
      weight (<1 kDa) fractions. More resistant peptides were generally rich in proline
      and glutamic acid. The role of in vitro digestion assays in dietary protein
      quality evaluation is discussed.

PMID- 16001872
TI  - Absorption of chemically unmodified lysine from proteins in foods that have
      sustained damage during processing or storage.
AB  - When a food is processed or stored, amino acids can react with a number of
      chemical entities to produce new compounds that are often nutritionally
      unavailable to the consumer. During acid hydrolysis used in amino acid analysis,
      some of these compounds revert back to the parent amino acid, leading to errors
      in estimates of both the amino acid content of foods and amino acid
      digestibility. This is a particular concern for the amino acid lysine in damaged
      food proteins. Chemical assays have thus been developed to allow determination of
      unaltered or reactive lysine. However, there is evidence that, in damaged food
      proteins, not all of the reactive lysine is released during digestion and
      absorbed. The development and application of an assay for absorbed (ileal
      digestible) reactive lysine is discussed.

PMID- 16001873
TI  - Bioactive peptides derived from food.
AB  - As interest in the ability of functional foods to impact on human health has
      grown over the past decade, so has the volume of knowledge detailing the
      beneficial roles of food-derived bioactive peptides. Bioactive peptides from both
      plant and animal proteins have been discovered, with to date, by far the most
      being isolated from milk-based products. A wide range of activities has been
      described, including antimicrobial and antifungal properties, blood pressure
      lowering effects, cholesterol-lowering ability, antithrombotic effects,
      enhancement of mineral absorption, immunomodulatory effects, and localized
      effects on the gut. Although there is still considerable research to be performed
      in the area of food-derived bioactive peptides, it is clear that the generation
      of bioactive peptides from dietary proteins during the normal digestive process
      is of importance. Therefore, it will become necessary when determining dietary
      protein quality to consider the potential effects of latent bioactive peptides
      that are released during digestion of the protein.

PMID- 16001874
TI  - Effects of antinutritional factors on protein digestibility and amino acid
      availability in foods.
AB  - Digestibility of protein in traditional diets from developing countries such as
      India, Guatemala, and Brazil is considerably lower compared to that of protein in
      typical North American diets (54-78 versus 88-94%). The presence of less
      digestible protein fractions, high levels of insoluble fiber, and high
      concentrations of antinutritional factors in the diets of developing countries,
      which are based on less refined cereals and grain legumes as major sources of
      protein, are responsible for poor digestibility of protein. The effects of the
      presence of some of the important antinutritional factors on protein and amino
      digestibilities of food and feed products are reviewed in this chapter. Food and
      feed products may contain a number of antinutritional factors that may adversely
      affect protein digestibility and amino acid availability. Antinutritional factors
      may occur naturally, such as glucosinolates in mustard and rapeseed protein
      products, trypsin inhibitors and hemagglutinins in legumes, tannins in legumes
      and cereals, phytates in cereals and oilseeds, and gossypol in cottonseed protein
      products. Antinutritional factors may also be formed during heat/alkaline
      processing of protein products, yielding Maillard compounds, oxidized forms of
      sulfur amino acids, D-amino acids, and lysinoalanine (LAL, an unnatural amino
      acid derivative). The presence of high levels of dietary trypsin inhibitors from
      soybeans, kidney beans, or other grain legumes can cause substantial reductions
      in protein and amino acid digestibilities (up to 50%) in rats and pigs.
      Similarly, the presence of high levels of tannins in cereals, such as sorghum,
      and grain legumes, such as fababean (Vicia faba L.), can result in significantly
      reduced protein and amino acid digestibilities (up to 23%) in rats, poultry, and
      pigs. Studies involving phytase supplementation of production rations for swine
      or poultry have provided indirect evidence that normally encountered levels of
      phytates in cereals and legumes can reduce protein and amino acid digestibilities
      by up to 10%. D-amino acids and LAL formed during alkaline/heat treatment of
      proteins such as casein, lactalbumin, soy protein isolate, or wheat proteins are
      poorly digestible (less than 40%), and their presence can reduce protein
      digestibility by up to 28% in rats and pigs. A comparison of the protein
      digestibility determination in young (5-week) versus old (20-month) rats suggests
      greater susceptibility to the adverse effects of antinutritional factors in old
      rats than in young rats. Therefore, the inclusion of protein digestibility data
      obtained with young rats, as the recommended animal model, in the calculation of
      PDCAAS (Protein Digestibility-Corrected Amino Acid Score) may overestimate
      protein digestibility and quality of products, especially those containing
      antinutritional factors, for the elderly. For products specifically intended for
      the elderly, protein digestibility should be determined using more mature rats.

PMID- 16001876
TI  - A valuable resource for the young dentist.

PMID- 16001875
TI  - The Protein Digestibility-Corrected Amino Acid Score (PDCAAS)--a concept for
      describing protein quality in foods and food ingredients: a critical review.
AB  - Protein Digestibility-Corrected Amino Score (PDCAAS) is discussed. PDCAAS is now
      widely used as a routine assay for protein quality evaluation, replacing the more
      traditional biological methods [e.g., measurement of the Protein Efficiency Ratio
      (PER) in rats]. PDCAAS is based on comparison of the essential amino acid content
      of a test protein with that of a reference essential amino acid pattern and a
      correction for differences in protein digestibility as determined using a rat
      assay. Although PDCAAS is a rapid and useful method, it often shows discrepancies
      when compared to PER values. These discrepancies relate to the following issues:
      uncertainty about the validity of reference patterns, invalidity of correction
      for fecal (versus ileal) digestibility, truncation of PDCAAS values to 100%,
      failure to obtain full biological response after supplementation of the limiting
      essential amino acid, discrepancies between protein and amino acid digestibility,
      effects of processing on protein quality, and effects of the presence of
      antinutritional factors in the matrix containing the protein. Part of the
      discrepancy between PDCAAS and PER can be overcome by modifications of PDCAAS.
      This article describes some proposed modifications and puts forward the
      suggestion that the rat protein fecal digestibility assay be replaced by an in
      vitro ileal amino acid digestibility assay based on a computer-controlled
      gastrointestinal model.

PMID- 16001877
TI  - The first and final word in patient satisfaction is communication.

PMID- 16001878
TI  - 10 ways new dentists benefit from organized dentistry.

PMID- 16001879
TI  - Are you a family business or a family business?

PMID- 16001880
TI  - Keeping it together: work-life balance.

PMID- 16001881
TI  - Buyer beware: practice value drops without team buy-in.

PMID- 16001882
TI  - Technological tools of the trade.

PMID- 16001883
TI  - Negotiating a fair compensation package.
AB  - At the end of the day, compensation packages must be fair for both you and your
      employer. Employers should conduct an economic analysis to determine what they
      can afford to offer and calculate the economic return that they should rightfully
      receive. Understanding the employer's side of the equation is equally important
      in developing a win/win compensation package for yourself.

PMID- 16001884
TI  - Business format guidelines for buying a practice.

PMID- 16001885
TI  - What are the tax issues in acquiring a dental practice?

PMID- 16001886
TI  - Taking the mystery out of reviewing third-party contracts.

PMID- 16001887
TI  - A clinico-pathologic correlation. Spindle cell carcinoma.

PMID- 16001888
TI  - Backup! Backup! Backup!

PMID- 16001889
TI  - Amalgam tattoo.

PMID- 16001890
TI  - Chew on this.

PMID- 16001891
TI  - [Cochlear implantation in patients with otitis media-related lesions].
AB  - OBJECTIVE: To present the experiences of cochlear implantation (CI) in patients
      with otitis media-related lesions. METHOD: Of the 9 patients with otitis media
      related lesions studied for cochlear implantation, one was implanted cochlear in
      second-stage operation after mastoidectomy and received reconstruction of the
      posterior ear canal wall with cartilage with perichondrium; one with chronic
      otitis media (perforation) had CI and tympanoplasty with cartilage with
      perichondrium in one-stage operation; three with silent otitis media had CI and
      modified mastoidectomy in one-stage operation; three with mastoid dysplasia and
      middle ear adhesions had CI and tympanic exploration in one-stage operation; one
      with cholesteatoma localizedin attic had CI and atticotomy and reconstruction
      with cartilage with perichondrium. RESULT: All devices worked properly. There
      were no otitis media-related complications. CONCLUSION: Patients with chronic
      suppurative otitis media must have all disease eradicated and do the utmost to
      reserve anatomic landmark before CI. Patients with silent otitis media can have
      CI in one-stage operation, if the drainage of Eustachian tube, attic and antrum
      is satisfying. Patients with cholesteatoma localizedin attic can have CI in one
      stage operation, but it is necessary to remove all lesions and reconstruct attic.
      The infection maybe an important cause of mastoid dysplasia and serious
      sensorineural deafness. Implanting electrode though the ear canal and promontony
      is a good method if the mastoid is sclerotic type and it is too difficult to
      implant though the facial recess. In order to avoid the retraction of drum and
      electrode dropping off, we can use cartilage with perichondrium to rebuild the
      drum, the posterior ear canal wall and the attic.

PMID- 16001892
TI  - [Oblique sagittal MRI of internal auditory canal applied before cochlear
      implantation].
AB  - OBJECTIVE: To explore practical value of oblique sagittal MRI of internal
      auditory canal (IAC) before cochlear implantation. METHOD: Fifteen patients(30
      ears) with sensorineural hearing loss who prepared to receive cochlear
      implantation were examined by oblique sagittal MRI (three dimensional T2-weighted
      fast spin echo) of IAC. RESULT: All patients have successfully completed oblique
      sagittal magnetic resonance imaging of IAC. The nerves in internal auditory canal
      were displayed distinctly. Thirteen patients with normal cochlear nerve had CI
      successfully, while 2 cases didn't receive CI due to abnormality of cochlear
      nerve. CONCLUSION: Oblique sagittal magnetic resonance imaging of internal
      auditory canal is a good method for evaluating development of cochlear nerve
      before cochlear implantation.

PMID- 16001893
TI  - [Misdiagnosis analysis of Wegener's granulomatosis in otorhinolaryngology].
AB  - OBJECTIVE: To investigate the early clinical features and development of
      Wegener's granulomatosis (WG), and to reduce the rate of misdiagnosis. METHOD:
      Retrospective analysis of 32 WG patients who consulted in otorhinolaryngology
      department primarily was carried out. RESULT: Among 32 cases, twenty-seven had
      been misdiagnosised (84%). Most of the cases were misdiagnosised as inflammation
      of otorhinolaryngology. CONCLUSION: Many cases of WG were consulted at
      otorhinolaryngology doctors primarily. Otolaryngological presentation may be as
      rhinitis, otitis media, facial palsy or laryngeal obstruction and so on. Patients
      with these presentations not responding to the standard treatment should be
      further investigated for a diagnosis of WG. Demanding history detailed, thinking
      highly of the status of lung and kidneys, analyzing the abnormal examinations
      overall are the key points to reduce the rate of misdiagnosis of WG.

PMID- 16001894
TI  - [Auditory brain stem response assessment in Ramsay Hunt syndrome].
AB  - OBJECTIVE: To discuss the changes of the auditory brain stem response in patients
      with Ramsay Hunt syndrome. METHOD: Thirty-six patients of Ramsay Hunt
      syndrome,who have only unilateral involvement with contralateral good ear, were
      studied with pure tone test and auditory brain stem response. The latencies of
      peaks I, III and V and interpeak latencies of I-III, I-V and III-V in bilateral
      ears were analyzed by SPSS 10.0 for windows. RESULT: Compared to the
      controlateral, the affected ears were significantly increased in latencies of II,
      V and interpeak latencies of I-III, I-V ( P < 0.05). CONCLUSION: The audiological
      data suggested that cochlear or retrocochlear involvement or involvement at more
      than one site along the auditory pathway existed in Ramsay Hunt syndrome, but
      pure cochlear hearing loss is not common.

PMID- 16001895
TI  - [The treatment of Semont maneuver for 40 patients with posterior semicircular
      canal benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To evaluate the effectiveness of Semont maneuver for posterior
      semicircular canal benign paroxysmal positional vertigo (PC-BPPV). METHOD: Forty
      patients with PC-BPPV were treated with Semont maneuver from January to August in
      2004. RESULT: After a single treatment session of Semont maneuver,the symptoms
      disappeared completely in 32 patients, the first success rate was 80%. Among 19
      patients who had only 1 week duration of PC-BPPU, the symptoms disappeared in 16
      patients after a single treatment. The symptoms disappeared in 3 patients after
      twice, 2 patients after 3 times and 1 patient after 4 times of Semont maneuver
      sessions, the total success rate was 95%. No effectiveness was found 2 patients;
      PC-BPPU recurred in 5 patients during follow-up and the recurrent rate was 12.5%.
      it was still effective for another Semont maneuver therapy session. CONCLUSION:
      The Semont maneuver therapy is safe and effective for PC-BPPV. Repeated Semont
      maneuver therapy is still effective for them.

PMID- 16001896
TI  - [Expression and significance of TERT and c-Myc oncogene protein product on
      cholesteatoma epithelium].
AB  - OBJECTIVE: To detect the expression and localization of human telomerase
      catalytic subunit (hTERT) and c-Myc oncogene protein product in human middle ear
      cholesteatoma, and to evaluate their roles in the proliferation of cholesteatoma
      epithelium. METHOD: The specimens from the middle ear cholesteatoma tissue of 32
      cases and external ear skin of 14 cases were examined by immunohistochemical SP
      method and computer image analysis system for TERT and c-Myc oncogene protein
      product. RESULT: All 32 samples of cholesteatoma showed a stronger expression of
      TERT and c-Myc oncogene protein product than that of the external ear skin. The
      indexes, such as mean positive cell rate and mean obsorbency of cholesteatoma
      epithelium are much higher than that of the normal external ear shin remarkably(
      P < 0.05). Accompanied with numerous inflammatory cells(lymphocytes, plasmocytes,
      neutrophils and macrophages) subcutaneously, the high expression of TERT and c
      Myc oncogene protein product were correlated with each other( P < 0. 05).
      CONCLUSION: Excessive proliferation and keratinization of cholesteatoma are
      presented by the expression of TERT and c-Myc oncogene protein product in
      different ways, both of which play a cooperative role in the development of
      cholesteatoma. Subcutaneous inflammatory response may contribute to the excessive
      proliferation of keratose cells.

PMID- 16001897
TI  - [Studying the effect of surgery for cholesteatoma in children].
AB  - OBJECTIVE: To study the impact of surgical treatment on hearing for cholesteatoma
      in children. METHOD: The retrospective survey was carried out in 62 children with
      cholesteatoma treated surgically over a 5-year period. Sixty patients had
      acquired cholesteatoma and two had congenital cholesteatoma. Forty-eight patients
      had extensive invasion that required canal wall-down mastoidectomy. Twelve
      patients with attic cholesteatoma underwent canal wall-up mastoidectomy, and 2
      patients with cholesteatoma localized to the middle-ear space were adequately
      treated with tympanic exploration. RESULT: Hearing was improved in 42 cases,
      preserved in 13 cases, became worse in 7 cases. A secondary surgical procedure
      for recidivistic (recurrent or residual) disease was performed in 3 cases. Facial
      paralysis was noted in 2 patients before surgical operation, and 2 patients had
      sensorineural hearing loss. CONCLUSION: This study confirmed the aggressiveness
      of cholesteatoma in children and demonstrated the need for careful preoperative
      evaluation, meticulous surgical technique, and prudent postoperative follow-up.

PMID- 16001898
TI  - [Dexamethasone pharmacokinetics in perilymph of guinea pig after different
      topical administrations].
AB  - OBJECTIVE: To determine pharmacokinetics profiles of dexamethasone (DEX) in
      perilymph of guinea pig with different intratympanic administrations, and to
      provide experimental evidence for clinical choice about administration. METHOD:
      Two different topical administrations placing a granule gelfoam soaked with DEX
      (10 g/L) in the niche of round window of guinea pig and infusing tympanic bulb
      with DEX solution (10 g/L) were conducted. Perilymph of the scala tympani was
      sampled 1-6 h after administration. DEX in the samples was assayed with high
      performance liquid chromatography. RESULT: The concentrations of DEX in perilymph
      after placing a granule gel-foam soaked with DEX in the niche of round window
      were significantly higher than that after intratympanic infusing. The half-life
      time of DEX after placing a granule gelfoam was longer. CONCLUSION: DEX could
      effectively penetrate round window membrane into perilymph after different
      intratympanic administrations, and the method of placing a granule gelfoam soaked
      with DEX in the niche of round window is more effective than that of
      intratympanic infusing.

PMID- 16001899
TI  - [Clinical analysis of non-Hodgkin lymphoma of the head and neck (report of 25
      cases)].
AB  - OBJECTIVE: To analyze the clinical presentation, staging, grading, and therapy of
      patients with non-Hodgkin lymphoma (NHL) of the head and neck. METHOD: A
      retrospective study of 25 patients with NHL of the head and neck was carried out
      in our hospital from March, 2000 to April, 2004. RESULT: Among 25 cases, 11 cases
      occurred in Waldeyer's ring that was the most common site of disease, 8 cases in
      nasal cavity, 1 case in paranasal sinuses, 4 cases in lymph nodes of the neck,
      and 1 case in salivary glands. Three patients with sinonasal tract lymphoma died.
      CONCLUSION: The prognosis of NHL of the head and neck is related to site, stage
      and histologic grade. And they are highly curable if treated appropriately.

PMID- 16001900
TI  - [The expression and significance of human beta-defensin 2 in middle ear
      cholesteatoma epithelium].
AB  - OBJECTIVE: To explore the effects of human beta-defensin 2 (hBD-2) in pathologic
      process of cholesteatoma by observing the expression of hBD-2 and the correlation
      of hBD-2 and density of Langhans cells(LC) in middle ear cholesteatoma. METHOD:
      The specimens from 21 cases of acquired middle ear cholesteatoma and 10 cases of
      external auditory canal skin (EACS) were examined by immunohistochemical method
      of hBD-2 and Langerhans cells (S-100 positive cells). RESULT: In EACS, hBD-2
      staining was faint while in the epithelium of cholesteatoma it was much stronger,
      there was significant difference between them( P < 0.01). Compared to that in
      EACS, the number of LC in the epithelium of cholesteatoma was increased. There
      was a strong correlation between elevated expression of hBD-2 and increased
      density of LC in the epithelium of cholesteatoma ( P < 0.05). CONCLUSION: hBD-2
      may play an important role in the inflammatory status of middle ear
      cholesteatoma. It maybe display chemotactic activity for LIangerhans cells (LC),
      and thus serves to link up innate and acquired immunity.

PMID- 16001901
TI  - [Distribution of gama-aminobutyric acid (GABA)ergic neurons in rats cochlear
      nuclei after unilateral cochlea ablation].
AB  - OBJECTIVE: To observe the distribution of gama-aminobutyric acid (GABA) ergic
      neurons in rats cochlear nuclei (CN) in pre-and post-operation of unilateral
      cochlea ablation. METHOD: The technique of direct anti-GABA immunocytochemistry
      (SP) was used in this study. RESULT: The GABAergic neurons existed extensively in
      cochlear nuclei(CN). The number was more, the volume was larger of GABAergic
      cells in CN and those cells were stained heavily before ablation. The number of
      GABAergic cells in lesion side was far less than that in intact side after
      unilateral cochlea ablation one to two weeks (P < 0.01), then the number of
      GABAergic cells increased after three weeks which was still less (P > 0.05) and
      almost reached normal after a month (P > 0.05). CONCLUSION: The changes of
      GABAergic neurons reflect the balance between excitatory and inhibitory of
      neurons. It suggests that changes in the extent of GABAergic inhibition have been
      shown to contribute to the reorganization of primary auditory central system
      after unilateral cochlea ablation in rats. The decrease and increase of the
      number of GABAergic-neurons are essential for this reorganization.

PMID- 16001902
TI  - [Exposing the rabbit cerebellopontine angle through post-sigmoid sinus approach
      and recording the direct compound action potential of the auditory nerve].
AB  - OBJECTIVE: To study the way of exposing the rabbit cerebellopontine angle through
      post-sigmoid sinus approach and recording the direct compound action potential of
      the auditory nerve, and to investigate the stability of DCAP N1 wave latency.
      METHOD: Fifteen New Zealand rabbits which had normal Preyer's auricle reflex were
      selected. Each one was studied in the left ear. After anaesthetized,the
      cerebellopontine angle of rabbits were exposed through post-sigmoid sinus
      approach under aseptic status,then the needle-shaped pole were inserted into the
      facial-acoustic nerve complex. The DCAP was recorded at the immediateness, 2 h
      and 5 h after the insertino sequentially. At last, DCAP N1 wave latencies of 15
      rabbits were statisticed and analyzed using paired-samples t-test. RESULT: To the
      15 sides, the distinct curves with well differentiated waves were induced in the
      all three times. No significant difference in any N1 wave latency had been found
      among the 3 times. CONCLUSION: The rabbit cerebellopontine angle could be exposed
      and the direct compound action potential of the auditory nerve could be recorded
      successfully by the way studied in this experiment. In normal state, the
      individual value of DCAP N1 wave latency is stable. During the process of surgery
      in which the cerebellopontine angle has been exposed, the DCAP N1 wave latency is
      a practical index for monitoring of hearing impairment.

PMID- 16001903
TI  - [Effect of adriamycin on expression of mdr1 gene in guinea pig cochlea lateral
      wall].
AB  - OBJECTIVE: To study whether ADM affect the expression of mdr1 gene in guinea pig
      cochlea lateral wall. METHOD: Sixty white guinea pigs with red eyes were divided
      into three groups: control group, NS group and ADM group. Guinea pigs were
      administered an intravenous injection of 30 mg/kg ADM. Four hoars later,ten
      animals were then immediately sacrificed, and the bony labyrinths were removed.
      The remaining ten animals were sacrificed after 24 h. The effect of ADM, an
      ototoxicity drug, on expression of mdrl gene in guinea pigs cochlea lateral walls
      were observed with RT-PCR. Furthermore, the ADM concentration in endolymph were
      measured by high performance liquid chromatography. RESULT: For ADM group, the
      density ratio of mdr1 to beta-action of the 24 h was significantly greater
      compared to that of the 4 h or controls; In contrast, the ADM concentration of 4
      h was significantly higher than that of the 24 h. CONCLUSION: mdr1 gene in normal
      guinea pig cochlea lateral wall is a stress gene. It can be induced by ADM; it
      may be not only related to reduce the accumulation of ototoxicity drug in
      endolymph, but also associated with the protective function of inner ear.

PMID- 16001904
TI  - Ultrasound imaging in rehabilitation: just a fad?

PMID- 16001905
TI  - The use of real-time ultrasound feedback in teaching abdominal hollowing
      exercises to healthy subjects.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To determine if
      supplementing typical clinical instruction with real-time ultrasound feedback
      facilitates performance and retention of the abdominal hollowing exercise (AHE).
      BACKGROUND: Increasingly clinicians are using real-time ultrasound imaging as a
      form of feedback when teaching patients trunk stabilization exercises; however,
      there has been no justification for this practice. METHODS AND MEASURES: Forty
      eight subjects were divided randomly into 3 groups that received different types
      of feedback: group 1 received minimal verbal feedback, group 2 received verbal
      and palpatory feedback, and group 3 received real-time ultrasound, verbal, and
      palpatory feedback. If the subject performed 3 consecutive correct AHEs during
      the initial session, she/he returned for a retention test. The performance of 3
      consecutive, correct AHEs was the criterion measure; the number of trials to
      criterion was also recorded during the initial and retention test sessions.
      RESULTS: The ability to perform the AHE differed among groups (P<.001). During
      the initial session, 12.5% of subjects in group 1, 50.0% of subjects in group 2,
      and 87.5% of subjects in group 3 were able to perform 3 consecutive AHEs. Group 3
      subjects achieved the criterion in fewer trials than the other 2 groups (P =
      .0006). No differences among groups were found for the retention testing;
      however, low power due to fewer subjects precluded a strong interpretation of
      this finding. CONCLUSION: Real-time ultrasound feedback can decrease the number
      of trials needed to consistently perform the AHE; however, the data are
      inconclusive with regard to retention of this skill.

PMID- 16001906
TI  - The use of ultrasound imaging of the abdominal drawing-in maneuver in subjects
      with low back pain.
AB  - STUDY DESIGN: Randomized controlled trial among patients with low back pain
      (LBP). OBJECTIVES: (1) Determine the reliability of real-time ultrasound imaging
      for assessing activation of the lateral abdominal muscles; (2) characterize the
      extent to which the abdominal drawing-in maneuver (ADIM) results in preferential
      activation of the transverse abdominis (TrA); and (3) determine if ultrasound
      biofeedback improves short-term performance of the ADIM in patients with LBP.
      BACKGROUND: Ultrasound imaging is reportedly useful for measuring and training
      patients to preferentially activate the TrA muscle. However, research to support
      these claims is limited. METHODS AND MEASURES: Thirty patients with LBP referred
      for lumbar stabilization training were randomized to receive either traditional
      training (n = 15) or traditional training with biofeedback (n = 15). Ultrasound
      imaging was used to measure changes in thickness of the lateral abdominal
      muscles. Differences in preferential changes in muscle thickness of the TrA
      between groups and across time were assessed using analysis of variance. RESULTS:
      Intrarater reliability measuring lateral abdominal muscle thickness exceeded
      0.93. On average, patients in both groups demonstrated a 2-fold increase in the
      thickness of the TrA during the ADIM. Performance of the ADIM did not differ
      between the groups. CONCLUSION: These data provide construct validity for the
      notion that the ADIM results in preferential activation of the TrA in patients
      with LBP. Although, the addition of biofeedback did not enhance the ability to
      perform the ADIM at a short-term follow-up, our data suggest a possible ceiling
      effect or an insufficient training stimulus. Further research is necessary to
      determine if there is a subgroup of patients with LBP who may benefit from
      biofeedback.

PMID- 16001907
TI  - Pharmacology in rehabilitation: nonsteroidal anti-inflammatory agents.
AB  - Nonsteroidal anti-inflammatory agents (NSAIDs) are the most commonly encountered
      over-the-counter (OTC) and prescription medications in physical therapy practice.
      Worldwide, over 73000000 prescriptions for nonsteroidal agents are written
      yearly. NSAIDs produce a wide range of beneficial effects to the physical therapy
      patient, enhancing the outcome of treatment. Helpful effects of NSAIDs include
      analgesia, antipyretic, anti-inflammatory, and antithrombotic properties.
      However, NSAIDs are also associated with frequent and significant side effects
      that are deleterious to treatment outcome, including delay in soft tissue and
      bone healing, renal and liver toxicity, hemorrhagic events, gastric irritation
      and ulceration, and central nervous system effects. Understanding of the
      pharmacological properties of these drugs, exemplified by aspirin, and the
      individual pharmacokinetics of specific preparations will help the therapist to
      screen patients for potential side effects, develop more effective plans of care,
      and, where allowed, effectively and safely prescribe NSAIDs.

PMID- 16001908
TI  - Use of lumbosacral region manipulation and therapeutic exercises for a patient
      with a lumbosacral transitional vertebra and low back pain.
AB  - STUDY DESIGN: Case report. BACKGROUND: A lumbosacral transitional vertebra (LTV)
      is a congenital anomaly that occurs in 3% to 21% of people with and without low
      back pain (LBP). There is lack of agreement in the literature as to whether or
      not the presence of a LTV may cause LBP. The objective of this case report is to
      present the use of lumbosacral region manipulation and therapeutic exercises on a
      patient with a known LTV and LBP. CASE DESCRIPTION: In this case report, an
      active-duty US Army soldier was referred to physical therapy with right-sided LBP
      and a lumbar radiograph showing a hemisacralized transitional L5 vertebra on the
      same side as his pain. The patient was treated with lumbosacral region
      manipulation and flexion exercises aimed at regaining total spinal motion and
      reducing pain. The patient responded favorably to spinal manipulation and
      exercise and was discharged from physical therapy after 4 visits. A modified
      Oswestry Low Back Pain Disability Questionnaire and inclinometer were used to
      measure outcome after physical therapy intervention. OUTCOMES: After a 2-week
      period of treatment in physical therapy, the patient improved from an initial
      Oswestry score of 32% to a score of 4%. Forward bending and left side bending
      improved from 74 degrees to 140 degrees and from 21 degrees to 45 degrees,
      respectively. DISCUSSION: Lumbosacral region manipulation along with therapeutic
      exercises appears to have been an effective treatment approach for this patient
      with LBP associated with a type IIA LTV.

PMID- 16001909
TI  - The effects of hamstring stretching on range of motion: a systematic literature
      review.
AB  - STUDY DESIGN: Systematic literature review. OBJECTIVE: Investigate the literature
      regarding the most effective positions, techniques, and durations of stretching
      to improve hamstring muscle flexibility. BACKGROUND: Hamstring stretching is
      popular among physical therapists, athletic trainers, and fitness/coaching
      professionals; however, numerous stretching methodologies have been proposed in
      the literature. This fact establishes a need to systematically summarize
      available evidence in an attempt to determine the most effective stretching
      approach. METHODS: A list of 28 pertinent manuscripts that included randomized
      and clinical trials was created according to specific inclusion/exclusion
      criteria. These manuscripts were critically reviewed for quality according to the
      Physiotherapy Evidence Database (PEDro) (10-point) scale and descriptive
      information about the stretching parameters employed in the research. RESULTS:
      Cumulatively, 1338 healthy subjects were included in the reviewed studies.
      Methodological quality scores ranged from 2 to 8 (mean +/- SD, 4.3 +/- 1.6).
      Several methodological flaws were frequently recognized, including failure to
      conceal group allocation or perform blinded assessment. All studies reported
      improvements in range of motion after stretching. CONCLUSIONS: Overall,
      methodological quality was poor, with only 21.4% (6/28) of studies achieving a
      score between 6 and 8. Thus it was difficult to confidently identify 1 most
      effective hamstring stretching method. Instead, the evidence appears to indicate
      that hamstring stretching increases range of motion with a variety of stretching
      techniques, positions, and durations.

PMID- 16001910
TI  - Norm references are essential if therapists are to correctly identify individuals
      who have physical limitations.

PMID- 16001911
TI  - Use of absorbable poly (d,l) lactic acid plates in cranial-vault remodeling:
      presentation of the first case and lessons learned about its use.
AB  - OBJECTIVE: To present the first clinical use of a new bioabsorbable material,
      poly (D,L) lactic acid (PDLLA), in pediatric cranial-vault remodeling procedures.
      This discussion will highlight the benefits and detriments of PDLLA in comparison
      with currently used absorbable plating systems. DESIGN: This was a case study
      documenting the first North American case in which PDLLA was used to treat
      craniosynostosis. MATERIALS AND METHODS: Evaluation of pure PDLLA, a copolymer
      product of the mixture of poly L-lactic acid and its D-isomer, was used in an 8
      month-old boy with a severe phenotypic expression of sagittal craniosynostosis.
      No signs of elevated intracranial pressure were present, and the neurological
      examination did not show impairments. Total cranial-vault remodeling with the
      "hung-span" technique was performed. The Resorb X system, containing 2.2-mm
      screws and 0.6- to 1-mm-thick plates, was used to stabilize the reconstructed
      cranial vault. RESULTS: No surgical complications occurred. The preoperative
      cranial index measured 62. The scaphocephalic appearance of the skull was
      eliminated, and the cranial index was normalized to 77. The screws and plates
      were less palpable than other plating systems. Twelve months postoperatively,
      none of the plates and screws were identifiable by external palpation.
      CONCLUSION: Resorb X has been successfully used in the treatment of sagittal
      craniosynostosis. Its rapid rate of resorption and lower profile make it an
      advantageous system for pediatric skull reconstruction. This represents the first
      use of this product in the United States for any pathology.

PMID- 16001912
TI  - Parental satisfaction with the CranioCap: a new cranial orthosis for
      deformational plagiocephaly.
AB  - OBJECTIVE: This study evaluates the safety and parent satisfaction of a new
      cranial orthosis designed to treat deformational plagiocephaly. DESIGN: A
      retrospective phone survey of parental satisfaction of a new cranial orthosis
      that has Food and Drug Administration (FDA) clearance for treatment of
      deformational plagiocephaly. SETTING: A tertiary referral center for children
      with craniofacial anomalies. PATIENTS: The first 232 consecutive infants enrolled
      in this program were retrospectively reviewed. INTERVENTIONS: Infants were
      entered in the cranial orthosis program if they had been diagnosed with
      deformational plagiocephaly and were less than 1 year of age, and if the infant's
      parents were interested in enrolling in a monitored cranial orthosis program.
      MAIN OUTCOME MEASURE: After completing therapy, a random sample of 81 parents
      (half completing treatment) was surveyed. Parents rated the improvement in their
      infant's head shape from 1 (least) to 5 (most). They were asked if they would
      repeat the program with a subsequent child. To date, 70% (162/ 232) have
      completed treatment. RESULTS: The orthosis was worn an average of 89 days. On
      average, parents rated head shape improvement 4.06 out of 5 (range, 3 to 5). Of
      parents surveyed, 81 (100%) would repeat the program with a subsequent child.
      There were three (3/232 or 1.3%) minor complications: one child with a persistent
      rash that resolved with termination of orthosis use, one child with a skin
      irritation that resolved with orthosis recontouring, and one child who could not
      be successfully fit. CONCLUSIONS: The CranioCap, a new cranial orthosis with
      clearance for treatment of deformational plagiocephaly, appears to be safe, well
      tolerated, and has excellent parent satisfaction.

PMID- 16001913
TI  - Treatment of osseous cleft palate defects: a preliminary evaluation of novel
      treatment modalities.
AB  - OBJECTIVE: To compare the use of autogenous iliac bone graft (ABG) alone with
      nonresorbable expanded polytetrafluoroethylene Gore-Tex TR membrane (GTM) and
      with ABG plus resorbable Resolut XT membrane barriers for the secondary closure
      of alveolar cleft defects. STUDY DESIGN: Fifteen patients aged 9 to 17 years with
      unilateral cleft palate were included in this study. All patients had primary
      closure of the soft tissues at infancy. Presurgical orthodontics and scaling
      preceded the surgery. The patients were randomized to one of three surgical
      treatment groups: (1) ABG, (2) GTM, or (3) autogenous bone plus resorbable
      membrane (ABM). Periapical radiographs were taken pretreatment and 2 to 6 years
      later and were used to measure changes in size (linear and area) of the osseous
      defect. RESULTS: Significant decreases were observed in mean initial defect width
      (9.8 to 6.7 mm; p = .0263), mean initial defect height (20.7 to 15.1 mm), and
      overall mean defect size (223.6 to 143.9 mm2). Greater improvement in mean defect
      width was observed for the ABM group (6.42 mm) compared with the ABG (1.22 mm)
      and GTM (1.38 mm) groups. The reduction in overall mean defect size was
      significantly greater in the ABM group (177 mm2) compared with the GTM (20.51
      mm2) and ABG (41.69 mm2) groups. CONCLUSION: Guided bone regeneration was found
      potentially useful for the treatment of osseous cleft palate defects. The
      combined approach yielded significantly greater defect fill. If further
      substantiated in larger independent studies, the adjunctive use of barrier
      membranes could improve the management of secondary closure of cleft palate
      defects.

PMID- 16001914
TI  - Psychosocial adjustment in children and adolescents with a craniofacial anomaly:
      age and sex patterns.
AB  - OBJECTIVE: To examine rates of psychosocial adjustment problems and competencies
      in a sample of children with congenital craniofacial anomalies (CFAs). METHODS:
      Retrospective chart review. SETTING: Urban hospital plastic surgery primary care
      unit. PATIENTS: A total of 724 children aged 2 to 18 years with completed Child
      Behavior Checklists in their medical charts. MAIN OUTCOME MEASURE: Child Behavior
      Checklist. RESULTS: Higher rates of problems in the clinical range were seen for
      withdrawn, attention, social, thought, and internalizing problems and lower rates
      for externalizing and somatic complaints; specific patterns varied according to
      age and sex. Elevated rates of competency deficits were seen in some groups.
      CONCLUSIONS: Most children with CFAs do not appear to experience psychosocial
      adjustment problems. Although elevated risk may be seen for certain problems,
      this group may be protected in other areas. Research identifying the mechanisms
      responsible for varying age and sex patterns of adjustment is needed.

PMID- 16001915
TI  - Evaluation of esthetic, functional, and quality-of-life outcome in adult cleft
      lip and palate patients.
AB  - OBJECTIVE: Evaluation of esthetic, functional, and health-related quality-of-life
      (HRQoL) outcomes in adult patients with a repaired cleft lip and palate. The
      treatment for all patients was based on the so-called Vienna concept.
      PATIENTS/DESIGN: Seventy adult patients with a repaired complete cleft lip and
      palate, ranging in age from 18 to 30 years, were included in the study. Esthetic
      and functional outcomes were assessed by the patients themselves and by five
      experts using a visual analog scale. Patients also completed the MOS Short-Form
      36 questionnaire to evaluate health-related quality of life. RESULTS: Patients
      rated their esthetic outcome significantly worse than the experts did. No
      significant differences were observed in the ratings for function. Female
      patients, especially, were dissatisfied with their esthetic outcomes. In a
      personal interview, nearly 63% of them asked for further treatment, particularly
      for upper-lip and nose corrections. The health-related quality-of-life
      questionnaire revealed low scores for only two subscales, namely social
      functioning and emotional role. In most subscales of health-related quality of
      life, patients who desired further treatment had significantly lower scores than
      did patients who desired no further treatment. CONCLUSION: Surgery of the lip and
      nose appears to be of prime importance for patients with a cleft lip and palate.
      Cleft patients who do not request secondary treatment are not always satisfied
      with the treatment. Patients with realistic expectations in regard to further
      treatment should be treated by specialists, whereas those with unrealistic
      expectations should be referred to a clinical psychologist.

PMID- 16001916
TI  - Dermatoglyphic pattern types in subjects with nonsyndromic cleft lip with or
      without cleft palate (CL/P) and their unaffected relatives in the Philippines.
AB  - OBJECTIVE: To investigate dermatoglyphic patterns in 95 nonsyndromic Filipino
      subjects with nonsyndromic cleft lip with or without cleft palate (CL/P) and 90
      of their unaffected relatives. DESIGN: Retrospective study of dermatoglyphic
      pattern types. SETTING: Negros Occidental and Cavite in the Philippines.
      PARTICIPANTS: Nonsyndromic subjects with CL/P and their unaffected relatives.
      METHODS: Dermatoglyphic patterns were categorized as arch, ulnar loop, radial
      loop, whorl, or other by three independent raters. Pattern data from the
      subjects, the unaffected relatives, and an unaffected control population (from
      the literature) were compared using chi-square tests. As a measure of asymmetry,
      dissimilarity between pattern types on homologous fingers was quantified and
      compared using Student's t tests. RESULTS: The frequency of arches (p = .016) and
      ulnar loops (p = .04) were significantly increased, and whorls decreased in the
      affected group (p = .0015), compared with the unaffected group. Affected female
      subjects had significantly more ulnar loops and arches (p = .009 and p = .023,
      respectively) and fewer whorls (p < .0001) than the unaffected female subjects.
      There were no significant differences between affected and unaffected male
      subjects. Dissimilarity scores were significantly different between male and
      female subjects and between subjects with CL/P and unaffected relatives.
      Additionally, pattern type frequencies for the relatives fell in between the
      frequencies for the CL/P group and the controls. CONCLUSIONS: In this Filipino
      population, differences in frequency of dermatoglyphic pattern types and pattern
      dissimilarity exist between individuals with orofacial clefts and their
      unaffected relatives and between both groups and controls, with the major effect
      seen in female subjects.

PMID- 16001917
TI  - Maternal obesity and the risk for orofacial clefts in the offspring.
AB  - OBJECTIVE: To estimate whether obese women have an increased risk of orofacial
      clefts in their offspring, compared with average-weight women. DESIGN AND
      PARTICIPANTS: The study was based on information on maternal body mass index
      (BMI) collected in early pregnancy and on the existence of orofacial clefts in
      the offspring, ascertained from multiple sources. The study included 1686 women
      who had infants with an orofacial cleft and as controls all delivered women (n =
      988,171) during the study period, 1992 through 2001. Infants with chromosome
      anomalies were excluded. The women were divided into underweight (BMI <19.8),
      average weight (reference group, BMI 19.8 to 26), overweight (BMI 26.1 to 29),
      and obese (BMI >29). Adjustments were made for year of birth, maternal age,
      parity, and maternal smoking. RESULTS: Obese (BMI >29) mothers had an overall
      increased risk for having an infant with orofacial clefts: odds ratio 1.30 (95%
      confidence interval 1.11 to 1.53). This increased risk was higher when the cleft
      was associated with other major malformations than when it was isolated. There
      was no statistically significant difference between the risk estimates for cleft
      lip and cleft palate. CONCLUSIONS: In this large sample, a positive association
      appears between maternal obesity in early pregnancy and orofacial clefts in the
      offspring. The explanation for this association is not known, but a relationship
      with undetected type 2 diabetes is one possibility.

PMID- 16001918
TI  - Experimental aspects of the pathogenesis of Robin sequence.
AB  - OBJECTIVE: The Pierre Robin Sequence (PRS) is a good example of disturbed
      embryonic development of the secondary palate involving insufficient mandibular
      growth, failed forward tongue movement, and, in the case of a cleft, impeded
      fusion of the secondary palate. Discussion continues regarding which of the
      involved pathogenetic factors is the primary cause of the induced cascade of
      signs: insufficient mandibular growth or failed descent of the tongue. DESIGN:
      Forty-five randomly selected, 18-day-old formalin-fixed A/WySn mouse fetuses were
      investigated. The strain is known to have a basic genetic defect and as much as
      44% clefts in the offspring. Twenty-four fetuses in the group had a cleft palate.
      Mandible position was measured relative to the head and to the presence or
      absence of a cleft. Cleft width and tongue position were also determined. Thirty
      eight NMRI mouse fetuses of the same age served as controls. RESULTS: All A/WySn
      fetuses showed marked mandibular retrognathia, which was more severe in the cleft
      group (p < .05), but there was no correlation between the degree of retrognathia
      and cleft width. The median cleft width was 3.4 mm (1.6 through 6.3 mm). The
      tongue was in the cleft in all 12 fetuses with wide clefts (>3.4 mm wide), and
      free in the oral cavity in the other 12. Tongue position did not influence the
      degree of retrognathia (p < .05). Moreover, the tongue was free in all fetuses
      with severe retrognathia. CONCLUSION: The results support the primary role of
      retroposition of the mandible in the development of cardinal symptoms of Pierre
      Robin Sequence.

PMID- 16001919
TI  - Multisite study of infants with single-suture craniosynostosis: preliminary
      report of presurgery development.
AB  - OBJECTIVE: To evaluate the cognitive and language development of untreated
      infants with a single suture craniosynostosis at time of diagnosis. DESIGN AND
      PARTICIPANTS: The study presents time 1 assessments on the first 100 infants with
      a single suture craniosynostosis (sagittal, metopic, unilateral coronal, and
      lambdoid) referred to the Infant Learning Project, a prospective, multisite,
      longitudinal study evaluating neurocognitive development. MAIN OUTCOME MEASURES:
      Infants were assessed with the mental (Mental Development Index [MDI]) and motor
      scales (Psychomotor Developmental Index [PDI]) of the Bayley Scales of Infant
      Development and the Preschool Language Scale receptive (PLS-AC) and expressive
      (PLS-EC) language scales. Mothers completed the Parenting Stress Inventory, a
      brief measure of intelligence (maternal IQ [MAT-IQ]), and provided information
      regarding family socioeconomic status (SES). RESULTS: As a group, infants scored
      significantly lower than the normative data on the MDI (91.9), PDI (83.5), PLS-AC
      (90.4), and PLS-EC (95.8), and the distribution of scores differed significantly
      from the expected distribution. MAT-IQ and SES were significantly correlated
      (.47, p < .01) with mothers of higher IQ coming from higher SES groups. Both MAT
      IQ and SES were significantly negatively correlated with life stress events;
      however, neither MAT-IQ nor SES was correlated with any of the infant development
      scores. CONCLUSIONS: There may be a greater developmental risk for infants with a
      single suture craniosynostosis than previously believed. However, control group
      data will be necessary to confirm findings.

PMID- 16001920
TI  - Early assessment of dental arch development in repaired unilateral cleft lip and
      unilateral cleft lip and palate versus controls.
AB  - OBJECTIVE: To evaluate dental arch relationships and dimensions, relative to an
      age matched noncleft sample, in Caucasian 3-year-old children with repaired
      unilateral cleft lip (UCL) or unilateral cleft lip and palate (UCLP). DESIGN:
      Prospective, cross-sectional, case-control study performed in Scotland, U.K.
      PARTICIPANTS: Eleven children with repaired unilateral cleft lip, 16 children
      with repaired unilateral cleft lip and palate, and 78 children as controls. MAIN
      OUTCOME MEASURES: Dental arch relationships and linear arch dimensions. RESULTS:
      Prevalence of Class III incisor relationship was 31.3% in children with
      unilateral cleft lip and palate compared with 9.1% in children with unilateral
      cleft lip. A buccal crossbite was present in 36% of children with unilateral
      cleft lip, compared with 75.6% of children with unilateral cleft lip and
      palate.Mean linear maxillary arch dimensions did not differ significantly between
      children with unilateral cleft lip and the controls. Except for second intermolar
      width, statistically significant differences existed in mean linear maxillary
      arch dimensions between the unilateral cleft lip and the unilateral cleft lip and
      palate groups; the mean linear maxillary arch dimensions were significantly
      greater in the control group than in the unilateral cleft lip and palate group.
      The mean cleft-affected anterior quadrant length appeared to be the arch
      dimension with the greatest power of discrimination among the three groups. There
      were no significant differences in mean linear mandibular arch dimensions among
      the three groups. CONCLUSIONS: Anterior crossbite was almost three times more
      common in the unilateral cleft lip and palate group than in the unilateral cleft
      lip group. Mean linear maxillary arch dimensions differed significantly between
      the unilateral cleft lip and palate group and the control group. There were no
      significant differences in mean linear maxillary arch dimensions between
      unilateral cleft lip and controls or between mean linear mandibular arch
      dimensions for unilateral cleft lip, unilateral cleft lip and palate, and
      controls.

PMID- 16001921
TI  - Difference in the prevalence of enamel alterations affecting central incisors of
      children with complete unilateral cleft lip and palate.
AB  - OBJECTIVE: To evaluate the prevalence of enamel alterations affecting the
      deciduous and permanent central maxillary incisors of children with complete
      unilateral cleft lip and palate and to verify their characteristics. DESIGN:
      Cross-sectional. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies
      University of Sao Paulo, Bauru, Sao Paulo, Brazil. PATIENTS: A sample of 90
      patients attending the Hospital for Rehabilitation of Craniofacial Anomalies,
      presenting with complete cleft lip and palate, of both genders, ages 2 to 11
      years old. METHODOLOGY: The buccal surfaces of the maxillary central incisors of
      patients were analyzed for observation of the presence of enamel defects, their
      type, number, and location. The prevalence of defects was compared between
      deciduous and permanent teeth and between the incisors at the cleft and noncleft
      sides. RESULTS: There was a higher frequency of defects among incisors on the
      cleft side for both deciduous and permanent dentitions compared with the noncleft
      side (p < .05); the permanent central incisor was more frequently affected than
      the deciduous. Evaluation of the types of defects for both incisors in both
      dentitions demonstrated a homogeneous distribution, except for a lower proportion
      of yellow opacity in the permanent dentition on the cleft side. In general, the
      most affected area in all dentitions was the incisal third. CONCLUSION: The
      prevalence of enamel alterations affecting incisors adjacent to the cleft was
      higher than for incisors on the noncleft side. This difference also was present
      in the permanent dentition.

PMID- 16001922
TI  - Three-dimensional nasal changes following nasoalveolar molding in patients with
      unilateral cleft lip and palate: geometric morphometrics.
AB  - OBJECTIVE: To evaluate three-dimensional changes in nasal morphology in patients
      with unilateral cleft lip and palate treated with presurgical nasoalveolar
      molding (NAM) to correct naso-labio-alveolar deformity. DESIGN: This was a
      prospective, longitudinal study. Digital stereophotogrammetry was used to capture
      three-dimensional facial images, and x, y, and z coordinates of 28 nasal
      landmarks were digitized. SAMPLE: Ten patients with unilateral cleft lip and
      palate. MAIN OUTCOME MEASURES: Nasal form changes between T1 (age: 28 +/- 2 days,
      pre-NAM) and T2 (age: 140 +/- 2 days, post-NAM), using conventional measurements
      and finite-element scaling analysis. RESULTS: Overall nasal changes were
      statistically different (p < .01), but no linear or curvilinear changes were
      found. Specifically, relative size increases were found on the noncleft side,
      involving the upper nose (30%), alar depth (20%), alar dome (30%), columella
      height (30%), and lateral wall of the nostril (17%). On the cleft side, the
      following showed a size increase: upper nose (8%), alar dome (5%), columella
      height (30%), and lateral wall of the nostril (30%). The cleft-side alar
      curvature, however, showed a large decrease in size (80%), but no changes on the
      noncleft side were found. Corresponding shape changes and angular changes were
      also found. CONCLUSIONS: Using NAM, bilateral nasal symmetry in patients with
      unilateral cleft lip and palate was improved before surgical repair. Furthermore,
      slight overcorrection of the alar dome on the cleft side using pressure exerted
      by the nasal stent is indicated to maintain the NAM result.

PMID- 16001923
TI  - A quantitative three-dimensional assessment of abnormal variations in the facial
      soft tissues of individuals with Down syndrome.
AB  - OBJECTIVE: To supply quantitative information about the facial soft tissues of
      subjects with Down syndrome by using summary anthropometric measurements. DESIGN,
      SETTING, AND PATIENTS: The three-dimensional coordinates of soft tissue facial
      landmarks were obtained using a computerized digitizer in 28 subjects with Down
      syndrome (11 girls and women and 17 boys and men aged 12 to 45 years) and 429
      healthy controls matched for sex, age, and ethnicity. From the landmarks, 18
      facial dimensions were calculated. Data were compared with those collected in
      healthy individuals by computing z-scores. Two summary anthropometric
      measurements for quantifying craniofacial variations were assessed in both the
      subjects with Down syndrome and the reference subjects: the mean z-score (an
      index of overall facial size) and its standard deviation, craniofacial
      variability index (an index of facial harmony). RESULTS: In subjects with Down
      syndrome, facial size was smaller than in normal individuals, and in 17 subjects
      the mean z-score fell outside the normal interval (mean +/- 2 SD). Twenty
      subjects had a craniofacial variability index larger than the normal interval.
      CONCLUSIONS: The facial soft tissue structures of subjects with Down syndrome
      differed from those of normal controls of the same age, sex, and ethnic group: a
      reduced facial size was coupled with a global anomalous relationship between
      individual measurements. The two indices allowed discriminating more than 89% of
      subjects with Down syndrome when compared with normal subjects.

PMID- 16001924
TI  - Cross-sectional study of the length of the nasal bone in cleft lip and palate
      subjects.
AB  - OBJECTIVE: The purpose of this study was to analyze the human nasal bone length
      in newborns and male adults with cleft lip (CL), cleft palate (CP), and
      unilateral cleft lip and palate (UCLP) and to compare the results to previous
      findings in prenatal material. DESIGN: This study was a radiographic profile
      cephalometric cross-sectional analysis. SUBJECTS AND METHODS: Profile radiographs
      from 60 newborns with a male-to-female ratio of 1:1 in each group (20 CL, 20 CP,
      and 20 UCLP) and 60 male adults (20 CL, 20 CP, and 20 UCLP) were randomly
      selected among radiographs, taken for optimizing the treatment planning. The
      nasal bone lengths (n-na) were measured with a digital caliper on the profile
      radiographs. To compare the nasal bone lengths in the different cleft groups,
      Student's t tests at a significant level at 5% were performed. RESULTS: Nasal
      bone length was significantly shorter in male adult patients with CL compared
      with patients with CP. Furthermore, the nasal bone length was significantly
      shorter in newborns with CL (2 months) compared to newborns with UCLP (2 months).
      A borderline significance was seen in the comparison of patients with CL and UCLP
      in male adults. There was no significant difference in the nasal bone length
      between the patients with CP and UCLP, in either the newborns or the male adults.
      CONCLUSIONS: Nasal bone length was significantly shorter in subjects with CL
      compared with subjects in whom the palate was clefted. The results show that the
      clefted lip in CL is associated with a subjacent skeletal deviation in the upper
      midface.

PMID- 16001925
TI  - Comparison of nasalance scores obtained with the Nasometer, the NasalView, and
      the OroNasal System.
AB  - OBJECTIVE: To compare nasalance scores obtained with the Nasometer, the
      NasalView, and the OroNasal System; evaluate test-retest reliability of the three
      systems; and explore whether three common text passages used for nasalance
      analysis could be shortened to a sentence each. SUBJECTS: Seventy-six adults with
      normal speech and hearing (mean age 26.5 years). PROCEDURES: Subjects read the
      complete Zoo Passage, Rainbow Passage, and Nasal Sentences. MAIN OUTCOME
      MEASURES: Mean nasalance magnitudes and mean nasalance distances were obtained
      with the three devices. RESULTS: The Nasometer had the lowest nasalance scores
      for the nonnasal Zoo Passage. The NasalView had the highest nasalance scores for
      the phonetically balanced Rainbow Passage. The OroNasal System had the lowest
      nasalance scores for the Nasal Sentences. The nasalance distance was largest for
      the Nasometer and smallest for the OroNasal System. Over 90% of the recordings
      were within 4% to 6% nasalance for most materials recorded with the Nasometer and
      the NasalView and within 7% to 9% for materials recorded with the OroNasal
      System. There were significant differences between the complete Zoo Passage and
      the Nasal Sentences and the individual sentences from these passages for the
      Nasometer and the OroNasal System. CONCLUSIONS: The three systems measure
      nasalance in different ways and provide nasalance scores that are not
      interchangeable. Test-retest variability for the Nasometer and the NasalView may
      be higher than previously reported. Individual sentences from the Zoo Passage and
      the Nasal Sentences do not provide nasalance scores that are equivalent to the
      complete passages.

PMID- 16001926
TI  - Immediate postoperative evaluation of the surgical wound and nutritional
      evolution after cheiloplasty.
AB  - OBJECTIVE: To evaluate the nutritional status and behavior of the surgical wound
      following cheiloplasty. SETTING: Hospital for Rehabilitation of Craniofacial
      Anomalies, University of Sao Paulo (HRAC/USP), Bauru, Sao Paulo, Brazil.
      PARTICIPANTS: Forty-five nursing children aged 3 to 13 months old, either bottle
      fed or spoon-fed, submitted to cheiloplasty during the study period. RESULTS: The
      results did not demonstrate significant differences between the study groups
      regarding gender, age, nutritional status, and condition of the surgical wound.
      Upon completion of the study, the infants of both groups were eutrophic,
      presenting increase in growth and development, with no hematoma, significant
      edema, sutural dehiscence, bleeding, or infection at the operated area.
      CONCLUSIONS: Both kinds of nursing, spoon- and bottle-feeding, had the same
      influence on nutritional status and wound condition in both study groups. We
      suggest that bottle-feeding should be tried in patients in the postoperative
      period of cheiloplasty, because this method was used after surgery without
      causing any damage to the lip surgical wound.

PMID- 16001928
TI  - Early composite cranioplasty in infants with severe aplasia cutis congenita: a
      report of two cases.
AB  - OBJECTIVE: Severe cutis aplasia congenita has traditionally been treated with
      initial soft tissue coverage and delayed cranioplasty. We advocate the technique
      of early composite reconstruction of both bone and soft tissues. METHODS: Two
      cases of cutis aplasia congenita with large skull defects (6 x 10 cm, 8 x 8 cm)
      of superficial layers, skull, and dura are presented. In each case, composite
      reconstruction was undertaken before 2 weeks of age with restoration of bony and
      soft tissue coverage through autologous, full-thickness cranial bone grafts and
      scalp flaps. Both children have been followed up over 2 years with clinical
      examination and computed tomography (CT) scans. RESULTS: In both cases, defects
      were completely repaired postoperatively and remained closed 2 years later.
      Complete regeneration of calvarial bone graft donor sites were documented by CT
      scan. Head shape and circumference were normal at 2-year follow up.

PMID- 16001927
TI  - Comparative evaluation of two different vestibuloplasty surgical procedures in
      cleft patients: a pilot study.
AB  - OBJECTIVE: Patients with a cleft lip or palate often present alterations in the
      labial aspect of the ridge, resulting in a shallow vestibule. This study compares
      the results of two different surgical procedures on deepening of the labial
      sulcus. INTERVENTIONS: Ten patients with a cleft lip and palate were separated
      into two groups and underwent different vestibuloplasty procedures. An
      experimental group used a removable retention splint. Preoperative and 4-month
      postoperative sulcus heights were measured and analyzed statistically. RESULTS:
      No statistically significant differences could be detected between groups.
      CONCLUSION: The results indicated that to reach consistent results, a larger
      number of patients must be submitted to this evaluation.

PMID- 16001929
TI  - Two cases of Tessier no. 4 cleft with anophthalmia.
AB  - OBJECTIVE: Tessier no. 4 cleft is a very rare craniofacial anomaly, and the
      primary surgical procedure has not been definitely standardized. The cheek
      advancement flap, technique, which was first reported by Van der Meulen (1985),
      has produced cosmetically favorable results. In this report, two cases with
      Tessier no. 4 cleft, which were treated with the cheek advancement flap
      technique, are presented. DESIGN AND PATIENTS: The first case was unilateral and
      the second was bilateral, and both were accompanied with anophthalmia on the
      cleft side. At the primary operation, dissection of the nasal soft tissue, medial
      canthopexy, and reconstruction of the lower eyelid and conjunctival fornix were
      performed. Cleft lip was repaired according to the rotation-advancement
      procedure. RESULTS AND CONCLUSIONS: Postoperative appearances were acceptable in
      both cases, because the resulting scars were made along the esthetic facial
      units. However, the soft tissue deficiency of the lower eyelid was prominent.
      Furthermore, in the unilateral case, caudal displacement of the palpebral fissure
      and cephalic deviation of the nasal ala was recognized.

PMID- 16001930
TI  - The Eurocleft Study: Intercenter study of treatment outcome in patients with
      complete cleft lip and palate.

PMID- 16001931
TI  - The Eurocleft Study: Intercenter study of treatment outcome in patients with
      complete cleft lip and palate.

PMID- 16001933
TI  - [Pulmonary changes in cirrhotic patients--update on an old problem].

PMID- 16001934
TI  - [Gasometric alterations in hospitalized cirrhotic patients].
AB  - BACKGROUND AND OBJECTIVES: Gas exchange alterations have been described in
      cirrhotic patients; but by the moment, a few prospective studies have focused in
      them. The aim of this study was to describe the frequency and severity of
      gasometric alterations in hospitalized cirrhotic patients, a their correlation
      with hepatocellular disfunction. PATIENTS AND METHODS: 50 consecutive cirrhotic
      patients (41 males) admitted for liver decompensation (ascites, liver
      encephalopathy, alcoholic hepatitis and upper gastrointestinal bleeding) without
      acute or chronic cardiopulmonary disfunction were included in the study. Patients
      were classified according with Child-Pugh score (A, n = 13; B, n = 21; C, n =
      16). Severe alcoholic hepatitis (SAH) was confirmed in 7 patients. Arterial
      gasometry was performed in all patients before discharge. Contrast
      echocardiography was performed in any case of suspicion of hepatopulmonary
      syndrome (HPS). RESULTS: Light hypoxemia was observed (80.9 mmHg), without
      differences with Child-Pugh. Hypocapnia was significantly more evident in Child C
      than in A and B (31.2 +/- 3.1 vs. 38.1 +/- 4.3 y 36.3 +/- 5 mmHg; p < 0,05),
      respectively. Cirrhotic patients with SAH showed a significantly higher
      hypocapnia by comparison with others (31.2 +/- 3.1 vs. a 36.3+/-5 mmHg; p <
      0.05). In multivariate analysis, independent prognostic variables for hypocapnica
      were plasmatic levels of protrombin time, albumin and sodium. HPS was confirmed
      in 8 patients (16%). CONCLUSIONS: The most prevalent gas exchange abnormality in
      cirrhosis was the alteration of alveolar-arterial oxygen tension gradient,
      directly correlated with hepatocellur disfunction. Hypocapnia could be a
      compensatory mechanism or the result of the activation of central respiratory
      centres by non-depurated substances by the liver.

PMID- 16001935
TI  - [Incidence of febrile episodes in patients with multiple myeloma undergoing
      autologous peripheral blood stem cell transplantation].
AB  - BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) is a
      procedure frequently used as therapy for hematological malignancies, in which
      infectious complications are a major cause of morbimortality. The duration and
      intensity of neutropenia, indwelling central venous catheters, and mucosa
      chemotherapy-induced damage, contribute to increase infection rates. We have
      retrospectively review the incidence of febrile episodes and microbiological
      documented infections (MDI) in patients with multiple myeloma (MM) undergoing
      PBSCT. PATIENTS AND METHODS: We have retrospectively analyzed 56 PBSCT in
      patients diagnosed of MM between 1995 and 2002 in our hospital. RESULTS: 34
      patients showed fever: 19 fever of unknown origin; 5 clinically documented
      infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram
      positive. We observed 2 infections associated to indwelling central venous
      catheters and 1 MDI due to simplex Herpes Virus. Two patients died due to
      infectious complications. CONCLUSIONS: The incidence of febrile episodes in our
      patients is similar to those previously reported as well, duration of neutropenia
      associated to PBSCT. We have observed a slightly higher incidence of gram
      negative pathogens.

PMID- 16001936
TI  - [Study on bacteremia in the service of Internal Medicine of a group 2 hospital.
      Analysis of recent three years].
AB  - INTRODUCTION: Bacteremia remains one of the most relevant problems in infectious
      disease. The interest of this study was to know the presentation and development
      pattern of bacteremia in our environment, in order to best prevent and treat this
      entity. PATIENTS AND METHOD: A retrospective, no interventional study, on
      significant bacteremia detected in the Service of Internal Medicine of a
      secondary level hospital over three years was carried out. Through the study
      length, from January 1 2001 until December 31 2003, 4,719 blood cultures were
      processed by the Service of Microbiology; of these, 1964 (41.6%) were submitted
      by the Service of Internal Medicine. Results were positive in 336 (17.1%); of
      these, 18 (24.1%) correlated with episodes of true bacteremia, and 255 (75.9%)
      were deemed as contaminations. RESULTS: Overall, 81 episodes of true bacteremia
      were studied, from 77 patients (4 patients presented with 2 episodes). An
      incidence rate of 28.25 episodes per 1000 hospital admissions was estimated. Mean
      age was 72 years (95% CI: 68.62-75.38). Males over 60 years-old were predominant
      (51.9%). Bacteremia was community-acquired in 75.3% of cases, and nosocomial in
      24.7%. Commonest baseline diseases were elevated arterial blood pressure and
      diabetes mellitus. Bacteremia development was mostly related to genitourinary and
      vascular handling. Most of them were nephrourological (42.0%), respiratory
      (19.8%) and abdominal (13.6%) in origin. In our environment, Escherichia coli
      (33.0%) and Staphylococcus coagulase-negative (15.9%) were the most commonly
      isolated pathogens. Empiric antibiotic therapy was correct in 86.2% of cases;
      third generation cephalosporins were the most used. Overall mortality rate was
      16% (13 patients), and bacteraemia-related mortality was 61%. CONCLUSIONS: A high
      incidence of bacteremia episodes is noteworthy, as compared with series from
      other centers. The percentage of episodes due to Staphylococcus coagulase
      negative was significant, as it is the rule in recent years; thus, a thoroughly
      assessment of potential contaminants, as well as staff training in extraction
      techniques becomes necessary.

PMID- 16001937
TI  - [Tuberculosis epidemiological study in a third level hospital during 2001].
AB  - OBJECTIVES: Estimate the incidence and epidemiological and clinical
      characteristics of Tuberculosis (TB), analyzing the influence of factors such as:
      HIV infection, immigration, chronic diseases and styles of life. MATERIAL AND
      METHODS: Retrospective study of patients who have diagnosed of active TB
      (microbiological results positive) and latent tuberculosis (Mantoux positive)
      during the year 2001 in the Gregorio Maranon Hospital. The variables include
      epidemiological, microbiological, clinical and therapeutic features. RESULTS: We
      registered 78 patients with TB at hospital, with estimated incidence in health
      area of 11, 14 cases per 100,000 habitants. The mean age of were 41.98 years;
      with 43.6% HIV infected patients and 9% immigrants. The sputum was the sample
      most used for the microbiological diagnosis, we detected resistance in 30% of
      samples analyzed. The HIV infected patients had more frequent TB from
      reactivation (p=0,016). The primary site of disease was pulmonary (78%). One
      pulmonary infiltrate was more frequent in the thoracic X-ray. The 56% of our HIV
      infected patients had normal thoracic X-ray (p <0,05). The treatment more common
      was with four drugs and the 75% of our patients fulfilled the treatment; the HIV
      infected patients leaves the treatment more frequent. The global mortality was
      9%. CONCLUSIONS: Actually, in Madrid, the persons with HIV infection, injection
      drug abuse, immigration and elders in residential home were higher risk of
      infection for TB. For strict control of disease is need early diagnosis and
      supervision of treatment .

PMID- 16001938
TI  - [Multiple enterolithiasis, coexisting with bladder and gallbladder lithiasis,
      associated with colon adenocarcinoma].
AB  - Enteroliths are calculi primarily formed in the intestine. Enterolithiasis is a
      rare condition frequently associated with intestinal stasis. Usually it causes no
      symptoms in most cases, but it can be an important diagnostic clue in patients
      presenting intestinal occlusive symptoms. We report a case of multiple
      enterolithiasis, very infrequent pathology, coexisting with bladder and gall
      bladder lithiasis in a patient with colon adenocarcinoma. Diagnosis was made by X
      rays and CT images. Calculi were analysed by several methods: chemical, infrared
      spectroscopy, stereoscopic microscopy and atomic emission spectroscopy; they
      showed that caluli are made up of organic material and whilokita (calcium and
      magnesium ortophosphate). No risk factors for lithogenesis were found in this
      patient excluding the intestinal stasis caused by intestinal narrowing as a
      result of adenocarcinoma. Genetic factors are suggested as main contributors to
      hyperlithogenesis observed in this patient. The physiopathological conditions
      were studied in depth and literature about this subject reviewed.

PMID- 16001939
TI  - [Whipple's disease. Two new cases of an underdiagnosed disease].
AB  - Whipple's disease is a rare systemic infectious disease caused by the bacterium
      Tropheryma whippelii. Early diagnosis is essential. Whipple's disease is
      potentially fatal but responds dramatically to antibiotic treatment. The
      diagnosis is confirmed by means of polymerase chain reaction (PCR) technology.
      This analysis may be useful for monitoring the efficacy of therapy. The
      recommended treatment al present is administration of cotrimoxazole twice daily
      for one year. When CNS involvement occurs, it is recommended initial treatment
      with daily parenteral administration of streptomycin 1 g and 1.2 million units of
      benzyl penicillin (Penicillin G) over a period of 14 days.

PMID- 16001940
TI  - [Buerger's disease with intestinal ischemic involvement].
AB  - Buerger's disease is uncommon arterial disease that affects mainly young people
      with heavy smoking history. Ischemic symptoms of upper and lower extremities are
      clearly defined as the most common kind of presentation. Visceral arteries are
      rarely affected. We report a case of a 44 year old young female with Buerger's
      disease and mesenteric ischemic involvement, and a revision of the literature
      about Buerger's disease with visceral affection. Due to the extreme rarity of the
      intestinal involvement of Buerger's disease, the early diagnosis is difficult,
      for this reason all patients affected by Buerger's disease who present intestinal
      symptoms should be carefully evaluated. Aortography and early laparoscopic
      revision are very important to limit ischemic intestinal injury and later
      complications. If hemodynamic instability is present emergency laparotomy at the
      operating theatre is recommended.

PMID- 16001941
TI  - [Tuberculous chylothorax: case report and review of the literature].
AB  - Chylothorax is an unusual manifestation of tuberculous disease. Anecdotal cases
      of chylothorax due to Mycobacterium tuberculosis have been reported in the
      literature. We describe a case of tuberculous chylothorax and review the
      previously published cases. None of these cases was diagnosed by the application
      of polymerase chain reaction in pleural effusion. This test applied to different
      specimens has shown high specificity and sensitivity; for this reason, the
      routine use of this test, on pleural effusion, could be very useful, quick, and
      few aggressive in the diagnosis of tuberculous chylothorax, especially when chest
      X-ray is normal.

PMID- 16001942
TI  - [Mitral prosthetic valve and presyncope].
AB  - The incidence of mitral prosthetic valve thrombosis is low and generally
      dependent on low levels of anticoagulation. The clinical presentation is highly
      variable and ranges from asymptomatic patient though to arterial embolism or
      hemodynamic symptoms of valve obstruction. We report a case of a patient with
      presyncope and prosthetic mitral valve dysfunction with intermittent flow
      obstruction.

PMID- 16001943
TI  - [Controversies in infective endocarditis].
AB  - The infective endocarditis is defined mainly as the infection of the internal
      surface of the heart, affecting to the cardiac valves although it can also do it
      to the septos, the tendinosas cords or endocardio mural. Around the origin, the
      diagnosis and the treatment of the disease, a considerable controversy has taken
      place. In this sense, basic criteria exist that they define to the infective
      endocarditis; however, particular situations are appraised in which the
      meticulous study is essential from the patient, doing special reference to the
      origin agents and, more in particular, to the fungal endocarditis.

PMID- 16001944
TI  - [Severe fasting hypoglycemia secondary to tuberculosis cachexia].

PMID- 16001947
TI  - The ODAC chronicles: Part 5. Prostate cancer endpoints.

PMID- 16001949
TI  - 6th International Symposium and expert workshops on Leukemia and Lymphoma. 17-19
      March, 2005, Amsterdam, The Netherlands.

PMID- 16001950
TI  - Atrasentan: a novel and rationally designed therapeutic alternative in the
      management of cancer.
AB  - Endothelin axis deregulation triggers a series of events that ultimately activate
      proliferation, invasion, escape from programmed cell death, new vessel formation,
      abnormal osteogenesis and alteration of nociceptive stimuli. Atrasentan is a
      novel agent that effectively targets this pathway and is able to inhibit and/or
      reverse several of those events. Biologic and clinical activity in patients with
      prostate cancer has been demonstrated in a Phase III, placebo-controlled setting
      by the suppression of markers of biochemical prostate cancer progression and a
      delay in time to disease progression. Atrasentan represents a new therapeutic
      option in the management of prostate cancer, especially in those patients with
      bone metastases. However, its precise role in other diseases such as ovarian
      cancer is yet to be defined.

PMID- 16001951
TI  - Gemcitabine in metastatic breast cancer.
AB  - Gemcitabine is a pyrimidine antimetabolite which has shown activity in metastatic
      breast cancer both as a single agent, but also in various combination regimens.
      It is characterized by a unique mechanism of action which includes cytotoxic self
      potentiation, masked DNA chain termination and potent inhibition of DNA repair.
      The clinical application of gemcitabine is supported by a favorable toxicity
      profile. In metastatic breast cancer, several Phase II trials document the
      activity of gemcitabine in pretreated and unpretreated patients. In a single
      Phase III trial performed in elderly patients not pretreated, gemcitabine was
      inferior to epirubicin. High activity has, however, been obtained by the
      combination of gemcitabine with taxanes such as paclitaxel or docetaxel. In a
      randomized trial performed in anthracycline-pretreated patients, the combined use
      of gemcitabine and paclitaxel induced a significant improvement not only of
      response rate and time to disease progression, but also caused a significant
      increase in quality of life and survival when compared with paclitaxel alone. The
      combination of gemcitabine with vinorelbine and cisplatin has been validated in
      numerous Phase II trials and promises reliable activity in anthracycline- and/or
      taxane-pretreated patients. Triple-agent regimens such as
      gemcitabine/epirubicin/paclitaxel provided consistently high response rates in
      Phase II trials, but failed to show superiority over the 5
      fluorouracil/epirubicin/cyclophosphamide regimen in a randomized Phase III trial.
      Based on high response rates and pathological complete remission rates achieved
      by preoperative induction therapy with gemcitabine/epirubicin/taxane regimens,
      ongoing trials focus on the incorporation of gemcitabine into neoadjuvant and
      adjuvant regimens.

PMID- 16001952
TI  - Fulvestrant in the treatment of postmenopausal women with advanced breast cancer.
AB  - Fulvestrant is a new type of estrogen receptor antagonist with no agonist
      effects, and represents a valuable addition to the range of endocrine treatments
      available to treat postmenopausal women with advanced breast cancer. Fulvestrant
      binds, blocks and degrades the estrogen receptor, thereby retarding growth and
      progression of hormone-sensitive tumors. Two Phase III trials have demonstrated
      that fulvestrant is at least as effective as the third-generation aromatase
      inhibitor anastrozole in the treatment of advanced breast cancer following
      progression on antiestrogen therapy. In addition, a Phase III trial comparing
      fulvestrant with tamoxifen in postmenopausal women with advanced breast cancer
      showed similar efficacy and tolerability. Clinical trials are ongoing to evaluate
      different endocrine sequence options for postmenopausal women with breast cancer,
      and to evaluate the efficacy of fulvestrant in combination with anticancer agents
      that target other signaling pathways.

PMID- 16001953
TI  - Role of allogeneic stem cell transplantation in multiple myeloma.
AB  - Multiple myeloma is currently incurable using standard treatment regimens. While
      the introduction of high-dose chemotherapy with autologous stem cell rescue has
      been shown to increase overall survival when compared with chemotherapy alone,
      this strategy is palliative. Allogeneic stem cell transplantation provides the
      potential for long-term disease-free survival in a small proportion of patients,
      although its application has been limited by procedure-related mortality,
      reflecting the intensive myeloablative conditioning given. Recently, reduced
      intensity conditioning regimens have been developed in an attempt to reduce
      toxicity whilst preserving the allogeneic graft-versus-myeloma effect, therefore
      maintaining the potential for disease eradication. This review aims to examine
      the current position of allogeneic transplantation in the management of myeloma.

PMID- 16001954
TI  - Proteasome inhibition as a therapeutic strategy for hematologic malignancies.
AB  - The ubiquitin-proteasome pathway is a principal intracellular mechanism for
      controlled protein degradation and has recently emerged as an attractive target
      for anticancer therapies since several cell cycle regulators and modulators of
      apoptosis are degraded through this pathway. The current state of the field of
      proteasome inhibitors and their prototypic member, bortezomib, which was recently
      approved by the US Food and Drug Administration for the treatment of advanced
      multiple myeloma, is reviewed. Particular emphasis is placed on the preclinical
      research data that became the basis for eventual clinical applications of
      proteasome inhibitors, an overview of the clinical development of this exciting
      drug class in multiple myeloma, and an appraisal of possible uses in other
      hematologic malignancies, such as non-Hodgkin's lymphomas.

PMID- 16001955
TI  - Treatment of mantle cell lymphoma: targeting the microenvironment.
AB  - Mantle cell lymphoma is a distinct entity among the non-Hodgkin's lymphomas
      characterized by a specific chromosomal translocation, the t(11;14)(q13;q32),
      overexpression of cyclin-D1 and frequent disease manifestations at extranodal
      sites. Mantle cell lymphoma remains difficult to treat and belongs to the
      lymphomas with the poorest long-term outcome. Recent advances in our
      understanding of lymphoma biology suggest that both alterations of the lymphoma
      cells themselves and interactions with the microenvironment are important for the
      growth and survival of the malignant B-cell clone. This novel approach to therapy
      is being exploited by evaluating drugs such as bortezomib and thalidomide that
      target interactions between tumor cells and cells of the microenvironment. Thus,
      with the use of novel therapeutic interventions, it is hoped that clinicians will
      be able to improve the outcome of patients with mantle cell lymphoma.

PMID- 16001956
TI  - Treatment of hematologic malignancies and solid tumors by inhibiting IGF receptor
      signaling.
AB  - Insulin-like growth factors (IGF) and their receptors (IGF-1R) constitute a
      complex biologic system implicated in diverse regulatory levels of cell
      proliferation, viability, differentiation and metabolism. Extensive epidemiologic
      data have implicated the IGF/IGF-1R pathway in the establishment of human
      malignancies, consistent with experimental data on the role of this signaling
      cascade in promoting cell transformation, resistance to apoptosis, metastases and
      other aspects of the biology of human cancers. However, historically, the IGF/IGF
      1R pathway has not been viewed as an attractive target for therapeutic
      intervention. The widespread IGF-1R expression in normal tissues and its close
      homology to the insulin receptor had led to the assumption that IGF-1R inhibition
      would cause unacceptable toxicities in vivo. Even though neutralizing antibodies
      against human IGF-1R have been efficacious against xenograft tumors, a lack of
      reactivity against the host rodent receptor has confounded the assessment of its
      therapeutic index. Furthermore, the lack of a clear understanding of the relevant
      significance for neoplastic cells in the function of IGF-1R versus other growth
      factor receptors provided an additional disincentive for the study of this
      pathway. However, recent reports from the authors' group and others have shown
      that small molecule inhibitors of tyrosine kinase activity of IGF-1R can be
      safely and efficaciously administered in vivo in clinically relevant orthotopic
      models of human neoplasias, such as multiple myeloma. This article reviews the
      data that validated IGF-1R as a therapeutic target for a broad spectrum of
      malignancies and provides in vivo proof-of-concept for the use of selective IGF
      1R kinase inhibitors as primary antitumor therapy or in synergistic combination
      as chemosensitizers. These results have not only provided the rationale for
      clinical trials of small molecule IGF-1R inhibitors, but have also rekindled
      interest in other therapeutic modalities (e.g., monoclonal antibodies) aimed at
      suppressing the function of this critical pathway for tumor cell pathophysiology.

PMID- 16001957
TI  - Head and neck squamous cell carcinoma: optimizing the therapeutic index.
AB  - The four recent noteworthy strategies aimed at improving therapeutic outcomes for
      the curative treatment of head and neck squamous cancers include the development
      of altered fractionation regimens, integration of chemotherapy, incorporation of
      intensity-modulated radiation therapy and introduction of targeted biologic
      therapy. Clinical investigations during the last 30 years have demonstrated the
      benefits of biologically sound altered fractionation and concurrent
      chemoradiation regimens in improving locoregional control and overall survival.
      These results have contributed to redefining the standard of care, with the
      caveat that proper patient selection for those who will benefit from potentially
      toxic combined modality treatment regimens remains controversial. These benefits
      have come at the expense of increased acute toxicity (i.e., mucositis) and
      sometimes at the expense of late toxicity (i.e., fibrosis and dysphagia). There
      are two additional developments that may help to further widen the therapeutic
      ratio. Intensity-modulated radiation therapy allows for the delivery of a highly
      conformal 3D radiation dose distribution around intended targets, thereby
      limiting the volumes of mucosa receiving a high dose per fraction and high total
      doses. The technical basis for intensity-modulated radiation therapy delivery
      reopens many fractionation questions that are still being addressed and
      challenges us to determine which of these is optimal for use with intensity
      modulated radiation therapy alone or in combination with concurrent sensitizers.
      Finally, combined radiation therapy and biologic therapies directed at targets
      expressed predominately or exclusively by tumor cells have the promise to help
      increase tumor cell kill, while at least not substantially increasing normal
      tissue toxicity. These strategies are reviewed in a clinical context.

PMID- 16001958
TI  - Intensity-modulated radiation therapy for head and neck cancer.
AB  - Radiotherapy planning studies have confirmed dosimetric advantages of intensity
      modulated radiation therapy over conventional and conformal radiation therapy.
      Utilization of intensity-modulated radiation therapy is ideal in head and neck
      cancer patients. Critical structures can be spared due to sharp dose gradients
      and limited organ motion with correct immobilization. Initial clinical results
      have shown excellent locoregional control, in part due to the delivery of high
      doses to the target volume. Reductions in acute toxicities and xerostomia through
      parotid sparing have been notable benefits. However, long-term outcomes with
      regards to local control and late toxicities with intensity-modulated radiation
      therapy are still lacking. This review focuses on the implementation of intensity
      modulated radiation therapy for the treatment of head and neck cancers, with a
      specific focus on set-up uncertainties, dose prescription and target volume
      determination and delineation.

PMID- 16001959
TI  - Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's
      antigen delivery pathway.
AB  - Dendritic cells release large quantities of exosomes, known as dexosomes. These
      dexosomes are heat-stable, small vesicles (60-90 nm in diameter) made up of a
      lipid bilayer displaying an enrichment in sphingomyelin and a decrease in
      phosphatidylcholine content with no measurable asymmetry. They incorporate a
      characteristic set of proteins, including a large quantity of tetraspanins such
      as CD9 and CD81, all the known antigen presenting molecules (major
      histocompatibility complex class I and II, CD1 a, b, c and d) and the
      costimulatory molecule CD86. The function of dexosomes is to transfer antigen
      loaded major histocompatibility complex class I and II molecules, and other
      associated molecules, to naive dendritic cells, potentially leading to the
      amplification of the cellular immune response. In preclinical mouse models,
      antigen-loaded dexosomes elicit strong antitumor activity. Human dexosomes can be
      prepared ex vivo relatively easily from dendritic cells derived from monocytes
      isolated by leukapheresis of healthy individuals or cancer patients. The
      feasibility of using dexosomes as a cancer therapeutic vaccine has been tested in
      two Phase I clinical studies in melanoma and lung cancer patients, respectively.
      These studies demonstrate that dexosomes can be prepared from cancer patient
      blood cells and be safely administered. Clinical observations suggested that
      dexosomes can stimulate both the adaptive (T-cells) and innate (natural killer
      cells) cellular immune responses. This review focuses on the perspective of using
      dexosomes in cancer immunotherapy. Concepts for using the exosome pathway in
      other possible pharmacologic applications are also discussed.

PMID- 16001960
TI  - Chemoprevention of lung cancer: concepts and strategies.
AB  - Lung cancer develops in a stepwise fashion, with an accumulation of molecular
      alterations progressing through preinvasive steps to invasive disease. This
      progression could be arrested or reversed through pharmacologic treatments, which
      are known as cancer chemoprevention. Preclinical and clinical findings relating
      to different classes of candidate chemopreventive agents provide support for this
      strategy as an active and promising approach for controlling this disease.

PMID- 16001961
TI  - Urological training in Europe: similarities and differences.

PMID- 16001962
TI  - Androgen deficiency and hormone-replacement therapy.

PMID- 16001963
TI  - Diagnosis of urothelial carcinoma of the bladder using fluorescence endoscopy.
AB  - Bladder cancer is a frequent disease and represents the second most common
      genitourinary neoplasm. Although many aspects of the management of superficial
      bladder cancer are now well established, significant challenges remain, which
      influences patient outcome. Early detection and treatment of recurrent disease is
      required to optimize bladder preservation, reduce patient morbidity, and increase
      quality of life and survival. Fluorescence endoscopy, often referred to as
      'photodynamic diagnosis' (PDD), with intravesical application of photosensitizing
      agents, has been developed to enhance the early detection of bladder cancer.
      There is growing evidence that PDD using 5-aminolaevulinic acid (ALA), hexyl-ALA
      ester or hypericin enhances the detection of bladder cancer, particularly of high
      grade flat lesions. Furthermore, transurethral resection of bladder tumour under
      fluorescence guidance reduces the risk of recurrent tumours. However, the impact
      on the progression of disease remains unclear and must be investigated in
      prospective randomized trials.

PMID- 16001964
TI  - Principles of anaesthesia in urological surgery.
AB  - Anaesthesia for urological surgery poses particular challenges for the
      anaesthetist related to the patient population and procedure type. The aim of
      this article is to cover the general principles of anaesthesia, with dedicated
      sections relevant to practising urological surgeons. This represents vast amounts
      of knowledge that cannot be covered in one article. We will focus upon
      preoperative preparation for surgery and anaesthesia, perioperative management
      including monitoring and analgesia, and postoperative management including fluid
      balance, critical care and recovery. Significant proportions of urological
      surgical patients have some degree of renal failure and this may be related to
      the surgery required. Anaesthetic care of patients with chronic renal impairment
      and transplant surgery will be covered in a future review.

PMID- 16001965
TI  - Alpha-tocopheryl succinate selectively induces apoptosis in neuroblastoma cells:
      potential therapy of malignancies of the nervous system?
AB  - Vitamin E (VE) analogues, epitomized by alpha-tocopheryl succinate (alpha-TOS),
      are potent inducers of apoptosis and anti-cancer agents. Here, we tested their
      effect on the highly malignant N-type neuroblastoma (Nb) cells and their
      differentiated, neurone-like counterparts. Nb cells were highly susceptible to
      several VE analogues, while differentiated Nb cells were relatively resistant to
      alpha-TOS. The importance of caspase-9 rather than caspase-8, as judged by
      specific siRNAs studies, together with the loss of the inner mitochondrial
      potential, suggests that alpha-TOS triggers apoptosis in Nb cells via the
      mitochondrial pathway. Cultured Nb cells were sensitized to alpha-TOS by pre
      treatment with Bcl-2, Bcl-xL or Mcl-1 siRNAs, while the malignant cell line was
      more resistant to the vitamin E analogue when Bax was knocked down. In contrast,
      overexpression of Bcl-2 in Nb cells rendered them more resistant to alpha-TOS
      induced apoptosis. The resistance of differentiated Nb cells to alpha-TOS
      mediated apoptosis occurred via two modes: first, by up-regulation of the anti
      apoptotic Bcl-2 family proteins and second, by accumulation of decreased levels
      of reactive oxygen species when challenged with alpha-TOS. We conclude that alpha
      TOS is highly selective in killing malignant brain cancer cells while relatively
      inert toward differentiated neuronal cells, and that vitamin E analogues may be
      novel therapeutics for the treatment of tumours such as neuroblastomas.

PMID- 16001966
TI  - Sleep and wakefulness modulate gene expression in Drosophila.
AB  - In the mammalian brain, sleep and wakefulness are associated with widespread
      changes in gene expression. Sleep in fruit flies shares many features with
      mammalian sleep, but it is currently unknown to what extent behavioral states
      affect gene expression in Drosophila. To find out, we performed a comprehensive
      microarray analysis of gene expression in spontaneously awake, sleep-deprived and
      sleeping flies. Fly heads were collected at 4 am, after 8 h of spontaneous sleep
      or sleep deprivation, and at 4 pm, after 8 h of spontaneous wakefulness. As in
      rats, we found that behavioral state and time of day affect Drosophila gene
      expression to a comparable extent. As in rats, transcripts with higher expression
      in wakefulness and in sleep belong to different functional categories, and in
      several cases these groups overlap with those previously identified in rats.
      Wakefulness-related genes code for transcription factors and for proteins
      involved in the stress response, immune response, glutamatergic transmission, and
      carbohydrate metabolism. Sleep-related transcripts include the glial gene
      anachronism and several genes involved in lipid metabolism. Finally, the
      expression of many wakefulness-related and sleep-related Drosophila transcripts
      is also modulated by the time of day, suggesting an interaction at the molecular
      level between circadian and homeostatic mechanism of sleep regulation.

PMID- 16001967
TI  - Two domains within the first putative transmembrane domain of presenilin 1
      differentially influence presenilinase and gamma-secretase activity.
AB  - Presenilins (PS) are thought to contain the active site for presenilinase
      endoproteolysis of PS and gamma-secretase cleavage of substrates. The structural
      requirements for PS incorporation into the gamma-secretase enzyme complex,
      complex stability and maturation, and appropriate presenilinase and gamma
      secretase activity are poorly understood. We used rescue assays to identify
      sequences in transmembrane domain one (TM1) of PS1 required to support
      presenilinase and gamma-secretase activities. Swap mutations identified an N
      terminal TM1 domain that is important for gamma-secretase activity only and a C
      terminal TM1 domain that is essential for both presenilinase and gamma-secretase
      activities. Exchange of residues 95-98 of PS1 (sw95-98) completely abolishes both
      activities while the familial Alzheimer's disease mutation V96F significantly
      inhibits both activities. Reversion of residue 96 back to valine in the sw95-98
      mutant rescues PS function, identifying V96 as the critical residue in this
      region. The TM1 mutants do not bind to an aspartyl protease transition state
      analog gamma-secretase inhibitor, indicating a conformational change induced by
      the mutations that abrogates catalytic activity. TM1 mutant PS1 molecules retain
      the ability to interact with gamma-secretase substrates and gamma-secretase
      complex members, although Nicastrin stability is decreased by the presence of
      these mutants. gamma-Secretase complexes that contain V96F mutant PS1 molecules
      display a partial loss of function for gamma-secretase that alters the ratio of
      amyloid-beta peptide species produced, leading to the amyloid-beta peptide
      aggregation that causes familial Alzheimer's disease.

PMID- 16001968
TI  - Characterization of a novel D2-like dopamine receptor with a truncated splice
      variant and a D1-like dopamine receptor unique to invertebrates from
      Caenorhabditis elegans.
AB  - We have cloned two novel Caenorhabditis elegans dopamine receptors, DOP-3 and DOP
      4. DOP-3 shows high sequence homology with other D2-like dopamine receptors. As a
      result of alternative splicing, a truncated splice variant of DOP-3, DOP-3nf, was
      produced. Because of the in-frame insertion of a stop codon in the third
      intracellular loop, DOP-3nf lacks the sixth and seventh transmembrane domains
      that are found in the full-length DOP-3 receptor. Reporter gene assay showed that
      DOP-3 attenuates forskolin-stimulated cAMP formation in response to dopamine
      stimulation, whereas DOP-3nf does not. When DOP-3 was coexpressed with DOP-3nf,
      the ability to inhibit forskolin-stimulated cAMP formation was reduced. DOP-4
      shows high sequence homology with D1-like dopamine receptors unique to
      invertebrates, which are distinct from mammalian D1-like dopamine receptors.
      Reporter gene assay showed that DOP-4 stimulates cAMP accumulation in response to
      dopamine stimulation. These two receptors provide new opportunities to understand
      dopaminergic signaling at the molecular level.

PMID- 16001969
TI  - Human immunodeficiency virus type 1 envelope glycoprotein 120 induces
      cyclooxygenase-2 expression in neuroblastoma cells through a nuclear factor
      kappaB and activating protein-1 mediated mechanism.
AB  - Induction of cyclooxygenase-2 (COX-2) in the brain of people infected with human
      immunodeficiency virus type 1 (HIV-1) has been proposed as a cause of cognitive
      impairment in AIDS dementia. Here, we have analyzed the molecular mechanism by
      which its induction takes place in neuroblastoma cells. The HIV-1 envelope
      protein gp120 was able to induce COX-2 mRNA and protein in several human
      neuroblastoma cell lines, which express CXCR4 and CCR5 but not CD4. Moreover,
      gp120 induces COX-2 promoter transcription. Sequential deletions of the promoter
      show that deletion of a distal nuclear factor-kappaB (NF-kappaB) site abrogated
      gp120-dependent transcription. More importantly, overexpression of NF-kappaB
      inhibitory subunit, IkappaBalpha, completely abrogated gp120-induced COX-2
      activity. However, transfection of p65/relA NF-kappaB was not enough to induce
      COX-2 transcription, suggesting that NF-kappaB was necessary but not sufficient
      to control COX-2 transcription induced by gp120. In addition to NF-kappaB,
      activating protein-1 (AP-1) but not nuclear factor of activated T cells (NFAT)
      dependent transcription was induced by gp120. Transfection of a dominant negative
      mutant c-Jun protein, TAM-67, efficiently blocked the induction of COX-2 promoter
      by gp120, confirming AP-1 requirement. Moreover, gp120 rapidly activates the c
      Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein kinase
      phosphorylation. The importance of NF-kappaB and AP-1 in COX-2 promoter and
      protein induction was corroborated by using pharmacological NF-kappaB, p38 and
      JNK inhibitors.

PMID- 16001970
TI  - Functional assessment of glutamate clearance mechanisms in a chronic rat glaucoma
      model using retinal ganglion cell calcium imaging.
AB  - Using optical imaging of retinal ganglion cell (RGC) calcium dynamics in living
      intact retinal wholemount preparations, we tested whether RGCs in an experimental
      rat glaucoma model were more sensitive to exogenously applied glutamate as a
      result of deficient glutamate clearance mechanisms. In contrast to post-natal rat
      RGCs in purified cultures, in which the calcium influx induced by 200 microm NMDA
      and 10 microm glutamate was approximately equivalent, application of up to 500
      microm glutamate did not affect calcium levels in RGCs in retinal wholemounts,
      even though the RGCs responded to 200 microm NMDA. Glutamate (500 microm) did
      elicit a RGC calcium response in retinal wholemounts when glutamate transporters
      were inhibited pharmacologically with DL-threo-beta-benzyloxyaspartate,
      confirming the presence of glutamate clearance mechanisms in this intact retina
      preparation. The effect of glutamate was then assessed on retinas from rats with
      chronically elevated intraocular pressure in one eye, produced by the injection
      of hypertonic saline into an episcleral vein. Application of up to 500 microm
      glutamate had no effect on RGC calcium levels, while millimolar concentrations of
      glutamate induced a calcium signal in RGCs that was indistinguishable from that
      in fellow control retinas. Therefore, there was no evidence for a global defect
      in glutamate uptake in this rat model of experimental glaucoma. Imaging
      glutamatergic calcium dynamics of RGCs in retinal wholemounts represents a novel
      methodology to probe glutamate transporter function and dysfunction in an intact
      CNS tissue system.

PMID- 16001971
TI  - Identification of synaptic plasma membrane proteins co-precipitated with
      fibrillar beta-amyloid peptide.
AB  - The beta-amyloid peptide that is overproduced in Alzheimer's disease rapidly
      forms fibrils, which are able to interact with various molecular partners. This
      study aimed to identify abundant synaptosomal proteins binding to the fibrillar
      beta-amyloid (fAbeta) 1-42. Triton X-100-soluble proteins were extracted from the
      rat synaptic plasma membrane fraction. Interacting proteins were isolated by co
      precipitation with fAbeta, or with fibrillar crystallin as a negative control.
      Protein identification was accomplished (1) by separating the tryptically
      digested peptides of the protein pellet by one-dimensional reversed-phase HPLC
      and analysing them using an ion-trap mass spectrometer with electrospray
      ionization; and (2) by subjecting the precipitated proteins to gel
      electrophoretic fractionation, in-gel tryptic digestion and to matrix-assisted
      laser desorption/ionization time-of-flight mass measurements and post-source
      decay analysis. Six different synaptosomal proteins co-precipitated with fAbeta
      were identified by both methods: vacuolar proton-pump ATP synthase,
      glyceraldehyde-3-phosphate dehydrogenase, synapsins I and II, beta-tubulin and
      2',3'-cyclic nucleotide 3'-phosphodiesterase. Most of these proteins have already
      been associated with Alzheimer's disease, and the biological and
      pathophysiological significance of their interaction with fAbeta is discussed.

PMID- 16001972
TI  - The readthrough variant of acetylcholinesterase remains very minor after heat
      shock, organophosphate inhibition and stress, in cell culture and in vivo.
AB  - Acetylcholinesterase (AChE) exists in various molecular forms, depending on
      alternative splicing of its transcripts and association with structural proteins.
      Tetramers of the 'tailed' variant (AChE(T)), which are anchored in the cell
      membrane of neurons by the PRiMA (Proline Rich Membrane Anchor) protein,
      constitute the main form of AChE in the mammalian brain. In the mouse brain,
      stress and anticholinesterase inhibitors have been reported to induce expression
      of the unspliced 'readthrough' variant (AChE(R)) mRNA which produces a monomeric
      form. To generalize this observation, we attempted to quantify AChE(R) and
      AChE(T) after organophosphate intoxication in the mouse brain and compared the
      observed effects with those of stress induced by swimming or immobilization; we
      also analyzed the effects of heat shock and AChE inhibition on neuroblastoma
      cells. Active AChE molecular forms were characterized by sedimentation and non
      denaturing electrophoresis, and AChE transcripts were quantified by real-time
      PCR. We observed a moderate increase of the AChE(R) transcript in some cases,
      both in the mouse brain and in neuroblastoma cultures, but we did not detect any
      increase of the corresponding active enzyme.

PMID- 16001973
TI  - Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level
      correlates to the therapeutic response rate of fibrosarcomas and is mediated by
      regulation of apoptotic pathways.
AB  - BACKGROUND: Because of the high resistance rate of fibrosarcomas against
      cytotoxic agents clinical chemotherapy of these tumors is not established. A
      better understanding of the diverse modes of tumor cell death following cytotoxic
      therapies will provide a molecular basis for new chemotherapeutic strategies. In
      this study we elucidated the response of a fibrosarcoma cell line to clinically
      used cytostatic agents on the level of gene expression. METHODS: HT1080
      fibrosarcoma cells were exposed to the chemotherapeutic agents doxorubicin,
      actinomycin D or vincristine. Total RNA was isolated and the gene expression
      patterns were analyzed by microarray analysis. Expression levels for 46 selected
      candidate genes were validated by quantitative real-time PCR. RESULTS: The
      analysis of the microarray data resulted in 3.309 (actinomycin D), 1.019
      (doxorubicin) and 134 (vincristine) probesets that showed significant expression
      changes. For the RNA synthesis blocker actinomycin D, 99.4% of all differentially
      expressed probesets were under-represented. In comparison, probesets down
      regulated by doxorubicin comprised only 37.4% of all genes effected by this
      agent. Closer analysis of the differentially regulated genes revealed that
      doxorubicin induced cell death of HT1080 fibrosarcoma cells mainly by regulating
      the abundance of factors mediating the mitochondrial (intrinsic) apoptosis
      pathway. Furthermore doxorubicin influences other pathways and crosstalk to other
      pathways (including to the death receptor pathway) at multiple levels. We found
      increased levels of cytochrome c, APAF-1 and members of the STAT-family (STAT1,
      STAT3), while Bcl-2 expression was decreased. Caspase-1, -3, -6, -8, and -9 were
      increased indicating that these proteases are key factors in the execution of
      doxorubicin mediated apoptosis. CONCLUSION: This study demonstrates that
      chemotherapy regulates the expression of apoptosis-related factors in
      fibrosarcoma cells. The number and the specific pattern of the genes depend on
      the used cytotoxic drug. The response rates on the gene expression level, i.e.
      the number of genes regulated by the drugs actinomycin D, doxorubicin and
      vincristine, correlate to the clinical effectiveness of the drugs. Doxorubicin
      seems to exert its cytotoxic mechanism by regulating genes, which are involved in
      several different apoptosis regulating pathways. The exact knowledge of the genes
      affected by the drugs will help to understand the diverse modes of soft tissue
      sarcoma cell death in response to cytotoxic therapies.

PMID- 16001974
TI  - Global gene expression analysis in time series following N-acetyl L-cysteine
      induced epithelial differentiation of human normal and cancer cells in vitro.
AB  - BACKGROUND: Cancer prevention trials using different types of antioxidant
      supplements have been carried out at several occasions and one of the
      investigated compounds has been the antioxidant N-acetyl-L-cysteine (NAC).
      Studies at the cellular level have previously demonstrated that a single
      supplementation of NAC induces a ten-fold more rapid differentiation in normal
      primary human keratinocytes as well as a reversion of a colon carcinoma cell line
      from neoplastic proliferation to apical-basolateral differentiation. The
      investigated cells showed an early change in the organization of the
      cytoskeleton, several newly established adherens junctions with E-cadherin/beta
      catenin complexes and increased focal adhesions, all features characterizing the
      differentiation process. METHODS: In order to investigate the molecular
      mechanisms underlying the proliferation arrest and accelerated differentiation
      induced by NAC treatment of NHEK and Caco-2 cells in vitro, we performed global
      gene expression analysis of NAC treated cells in a time series (1, 12 and 24
      hours post NAC treatment) using the Affymetrix GeneChip Human Genome U95Av2 chip,
      which contains approximately 12,000 previously characterized sequences. The
      treated samples were compared to the corresponding untreated culture at the same
      time point. RESULTS: Microarray data analysis revealed an increasing number of
      differentially expressed transcripts over time upon NAC treatment. The early
      response (1 hour) was transient, while a constitutive trend was commonly found
      among genes differentially regulated at later time points (12 and 24 hours).
      Connections to the induction of differentiation and inhibition of growth were
      identified for a majority of up- and down-regulated genes. All of the observed
      transcriptional changes, except for seven genes, were unique to either cell line.
      Only one gene, ID-1, was mutually regulated at 1 hour post treatment and might
      represent a common mediator of early NAC action. The detection of several genes
      that previously have been identified as stimulated or repressed during the
      differentiation of NHEK and Caco-2 provided validation of results. In addition,
      real-time kinetic PCR analysis of selected genes also verified the differential
      regulation as identified by the microarray platform. CONCLUSION: NAC induces a
      limited and transient early response followed by a more consistent and
      extensively different expression at later time points in both the normal and
      cancer cell lines investigated. The responses are largely related to inhibition
      of proliferation and stimulation of differentiation in both cell types but are
      almost completely lineage specific. ID-1 is indicated as an early mediator of NAC
      action.

PMID- 16001975
TI  - The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing
      radiation by a DNA-PK-independent mechanism.
AB  - BACKGROUND: By modulating the expression levels of specific signal transduction
      molecules, the 26S proteasome plays a central role in determining cell cycle
      progression or arrest and cell survival or death in response to stress stimuli,
      including ionizing radiation. Inhibition of proteasome function by specific drugs
      results in cell cycle arrest, apoptosis and radiosensitization of many cancer
      cell lines. This study investigates whether there is also a concomitant increase
      in cellular radiosensitivity if proteasome inhibition occurs only transiently
      before radiation. Further, since proteasome inhibition has been shown to activate
      caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs,
      which is involved in DNA-double strand repair, the hypothesis was tested that
      caspase-3 activation was essential for both apoptosis and radiosensitization
      following proteasome inhibition. METHODS: Prostate carcinoma PC-3 cells were
      treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution,
      apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were
      monitored. Radiosensitivity was assessed using a clonogenic assay. RESULTS:
      Inhibition of proteasome function caused cell cycle arrest and apoptosis but this
      did not involve early activation of caspase-3. Short-time inhibition of
      proteasome function also caused radiosensitization but this did not involve a
      decrease in DNA-PKcs protein levels or DNA-PK activity. CONCLUSION: We conclude
      that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute
      to the radiosensitizing effects of MG-132.

PMID- 16001976
TI  - The necessary future of chiropractic education: a North American perspective.
AB  - The chiropractic educational system in North America is currently in a state of
      flux. The attempted conversion of some chiropractic schools into "universities"
      and the want of university affiliation for chiropractic schools suggests that we
      are searching for a better alternative to the present system. In the early 20th
      century, the Flexner Report helped transform modern medical education into a
      discipline that relies on scientific and clinical knowledge. Some have wondered
      if it is time for a Flexner-type report regarding the education of doctors of
      chiropractic. This article outlines the current challenges within the
      chiropractic educational system and proposes positive changes for that system.

PMID- 16001977
TI  - College campus smoking policies and programs and students' smoking behaviors.
AB  - BACKGROUND: Although tobacco use in the United States has declined over the past
      20 years, cigarette use among college students remains high. Additional research
      is thus needed to determine how university tobacco control policies and
      preventive education programs affect college students' smoking behaviors.
      METHODS: Approximately 13,000 undergraduate students at 12 universities or
      colleges in the state of Texas completed a web-based survey. College smoking
      policies were obtained from a survey of college administrators and from college
      websites. Logistic regression analyses were conducted to estimate the effects of
      individual smoking policies and programs on the odds of cigarette smoking.
      RESULTS: Of the individual programs, only having a preventive education program
      on campus was associated with lower odds of smoking. The existence of smoking
      cessation programs and designated smoking areas were associated with higher odds
      of smoking. Policies governing the sale and distribution of cigarettes were
      insignificantly associated with smoking. CONCLUSION: Rather than focusing on
      policies restricting cigarette sales and use, college administrators should
      consider implementing or expanding tobacco prevention and education programs to
      further reduce student smoking rates.

PMID- 16001978
TI  - Seroprevalence of hepatitis A infection in a low endemicity country: a systematic
      review.
AB  - BACKGROUND: In Canada--a low endemicity country, vaccines for hepatitis A virus
      (HAV) are currently recommended to individuals at increased risk for infection or
      its complications. Applying these recommendations is difficult because the
      epidemiology of HAV infection is poorly defined, complex, and changing. This
      systematic review aimed to 1) estimate age-specific prevalence of HAV antibody in
      Canada and 2) evaluate infection-associated risk factors. METHODS: MEDLINE (1966
      2005) and EMBASE (1980-2005) were searched to identify relevant studies for the
      systematic review. Archives for the Canada Diseases Weekly Report (1975-1991) and
      Canada Communicable Disease Report (1992-2005) were searched for relevant public
      health reports. Data were abstracted for study and participants' characteristics,
      age-specific prevalence, and risk factors. RESULTS: A total of 36 reports
      describing 34 unique studies were included.The seroprevalence in Canadian-born
      children was approximately 1% in ages 8-13, 1-6% in 20-24, 10% in 25-29, 17% in
      30-39, and increased subsequently. In age groups below 20 and 20-29, age-specific
      seroprevalence generally remained constant for studies conducted across
      geographic areas and over time. Compared to Canadian-born individuals, subjects
      born outside Canada were approximately 6 times more likely to be seropositive
      (relative risk: 5.7 [95% CI 3.6, 9.0]). Travel to high risk areas in individuals
      aged 20-39 was associated with a significant increase in anti-HAV seropositivity
      (RR 2.8 [1.4, 5.5]). Compared to heterosexuals, men having sex with men were only
      at a marginally higher risk (adjusted odds ratio 2.4 [0.9, 6.1]). High risk for
      seropositivity was also observed for Canadian First Nations and Inuit
      populations. CONCLUSION: Results from the current systematic review show that in
      this low endemicity country, disease acquisition occurs in adulthood rather than
      childhood. The burden of disease is high; approximately 1 in 10 Canadians had
      been infected by ages 24-29. The increase in prevalence in young adults coincides
      with disease importation and increasing frequency of risk factors, most likely
      behavioral-related ones. Gaps in seroprevalence data were identified rendering
      the application of current immunization recommendations difficult. A nationwide
      prevalence survey for all Canadians is needed. This is essential to quantify the
      effectiveness of current recommendations and conduct cost-effectiveness
      evaluations of alternative immunization programs, if necessary.

PMID- 16001979
TI  - IL-4 increases type 2, but not type 1, cytokine production in CD8+ T cells from
      mild atopic asthmatics.
AB  - BACKGROUND: Virus infections are the major cause of asthma exacerbations. CD8+ T
      cells have an important role in antiviral immune responses and animal studies
      suggest a role for CD8+ T cells in the pathogenesis of virus-induced asthma
      exacerbations. We have previously shown that the presence of IL-4 during
      stimulation increases the frequency of IL-5-positive cells and CD30 surface
      staining in CD8+ T cells from healthy, normal subjects. In this study, we
      investigated whether excess IL-4 during repeated TCR/CD3 stimulation of CD8+ T
      cells from atopic asthmatic subjects alters the balance of type 1/type 2 cytokine
      production in favour of the latter. METHODS: Peripheral blood CD8+ T cells from
      mild atopic asthmatic subjects were stimulated in vitro with anti-CD3 and IL-2 +/
      excess IL-4 and the expression of activation and adhesion molecules and type 1
      and type 2 cytokine production were assessed. RESULTS: Surface expression of very
      late antigen-4 [VLA-4] and LFA-1 was decreased and the production of the type 2
      cytokines IL-5 and IL-13 was augmented by the presence of IL-4 during stimulation
      of CD8+ T cells from mild atopic asthmatics. CONCLUSION: These data suggest that
      during a respiratory virus infection activated CD8+ T cells from asthmatic
      subjects may produce excess type 2 cytokines and may contribute to asthma
      exacerbation by augmenting allergic inflammation.

PMID- 16001980
TI  - Changes in P-glycoprotein activity are mediated by the growth of a tumour cell
      line as multicellular spheroids.
AB  - BACKGROUND: Expression of P-glycoprotein (P-gp), the multidrug resistance (MDR) 1
      gene product, can lead to multidrug resistance in tumours. However, the
      physiological role of P-gp in tumours growing as multicellular spheroids is not
      well understood. Recent evidence suggests that P-gp activity may be modulated by
      cellular components such as membrane proteins, membrane-anchoring proteins or
      membrane-lipid composition. Since, multicellular spheroids studies have evidenced
      alterations in numerous cellular components, including those related to the
      plasma membrane function, result plausible that some of these changes might
      modulate P-gp function and be responsible for the acquisition of multicellular
      drug resistance. In the present study, we asked if a human lung cancer cell line
      (INER-51) grown as multicellular spheroids can modify the P-gp activity to
      decrease the levels of doxorubicin (DXR) retained and increase their drug
      resistance. RESULTS: Our results showed that INER-51 spheroids retain 3-folds
      lower doxorubicin than the same cells as monolayers however; differences in
      retention were not observed when the P-gp substrate Rho-123 was used.
      Interestingly, neither the use of the P-gp-modulating agent cyclosporin-A (Cs-A)
      nor a decrease in ATP-pools were able to increase DXR retention in the
      multicellular spheroids. Only the lack of P-gp expression throughout the
      pharmacological selection of a P-gp negative (P-gpneg) mutant clone (PSC-1)
      derived from INER-51 cells, allow increase of DXR retention in spheroids.
      CONCLUSION: Thus, multicellular arrangement appears to alter the P-gp activity to
      maintain lower levels of DXR. However, the non expression of P-gp by cells
      forming multicellular spheroids has only a minor impact in the resistance to
      chemotherapeutic agents.

PMID- 16001981
TI  - Elevated ex vivo monocyte chemotactic protein-1 (CCL2) in pulmonary as compared
      with extra-pulmonary tuberculosis.
AB  - BACKGROUND: Tuberculosis causes 3 million deaths annually. The most common site
      of tuberculosis is pulmonary however; extra-pulmonary forms of the disease also
      remain prevalent. Restriction of Mycobacterium tuberculosis depends on effective
      recruitment and subsequent activation of T lymphocytes, mononuclear and
      polymorphonuclear cells to the site of infection. Tumor necrosis factor (TNF)
      alpha is essential for granuloma formation and is a potent activator of monocyte
      chemotactic protein (MCP-1, CCL2). CCL2 is essential for recruitment of monocytes
      and T cells and has been shown to play a role in protection against tuberculosis.
      Interleukin -8 (CXCL8) is a potent activator of neutrophils. Increased levels of
      CCL2, CXCL8 and TNFalpha are reported in tuberculosis but their significance in
      different forms of tuberculosis is as yet unclear. We have used an ex vivo assay
      to investigate differences in immune parameters in patients with either pulmonary
      or extra-pulmonary tuberculosis. METHODS: Serum levels of CCL2, CXCL8 and
      TNFalpha were measured in patients with pulmonary tuberculosis (N = 12), extra
      pulmonary tuberculosis (N = 8) and BCG-vaccinated healthy volunteers (N = 12).
      Whole blood cells were stimulated with non-pathogenic Mycobacterium bovis bacille
      Calmette Guerin (BCG) vaccine strain or bacterial lipopolysaccharide (LPS) and
      cyto/chemokines were monitored in supernatants. RESULTS: Circulating serum levels
      of CXCL8 and TNFalpha were raised in all tuberculosis patients, while CCL2 levels
      were not. There was no difference in spontaneous cytokine secretion from whole
      blood cells between patients and controls. M. bovis BCG-induced ex vivo CCL2
      secretion was significantly greater in pulmonary as compared with both extra
      pulmonary tuberculosis patients and endemic controls. In response to LPS
      stimulation, patients with pulmonary tuberculosis showed increased CCL2 and
      TNFalpha responses as compared with the extra-pulmonary group. BCG-, and LPS
      induced CXCL8 secretion was comparable between patients and controls. CONCLUSION:
      CCL2 is activated by TNFalpha and is essential for recruitment of monocytes and T
      cells to the site of mycobacterial infection. Increased CCL2 activation in
      pulmonary tuberculosis may result in a stronger cellular response as compared
      with extra-pulmonary tuberculosis patients, and this may contribute to the
      localization of infection to the pulmonary site.

PMID- 16001982
TI  - Histone acetylation and histone deacetylase activity of magnesium valproate in
      tumor and peripheral blood of patients with cervical cancer. A phase I study.
AB  - BACKGROUND: The development of cancer has been associated with epigenetic
      alterations such as aberrant histone deacetylase (HDAC) activity. It was recently
      reported that valproic acid is an effective inhibitor of histone deacetylases and
      as such induces tumor cell differentiation, apoptosis, or growth arrest. METHODS:
      Twelve newly diagnosed patients with cervical cancer were treated with magnesium
      valproate after a baseline tumor biopsy and blood sampling at the following dose
      levels (four patients each): 20 mg/kg; 30 mg/kg, or 40 mg/kg for 5 days via oral
      route. At day 6, tumor and blood sampling were repeated and the study protocol
      ended. Tumor acetylation of H3 and H4 histones and HDAC activity were evaluated
      by Western blot and colorimetric HDAC assay respectively. Blood levels of
      valproic acid were determined at day 6 once the steady-state was reached.
      Toxicity of treatment was evaluated at the end of study period. RESULTS: All
      patients completed the study medication. Mean daily dose for all patients was
      1,890 mg. Corresponding means for the doses 20-, 30-, and 40-mg/kg were 1245,
      2000, and 2425 mg, respectively. Depressed level of consciousness grade 2 was
      registered in nine patients. Ten patients were evaluated for H3 and H4
      acetylation and HDAC activity. After treatment, we observed hyperacetylation of
      H3 and H4 in the tumors of nine and seven patients, respectively, whereas six
      patients demonstrated hyperacetylation of both histones. Serum levels of valproic
      acid ranged from 73.6-170.49 microg/mL. Tumor deacetylase activity decreased in
      eight patients (80%), whereas two had either no change or a mild increase. There
      was a statistically significant difference between pre and post-treatment values
      of HDAC activity (mean, 0.36 vs. 0.21, two-tailed t test p < 0.0264). There was
      no correlation between H3 and H4 tumor hyperacetylation with serum levels of
      valproic acid. CONCLUSION: Magnesium valproate at a dose between 20 and 40 mg/kg
      inhibits deacetylase activity and hyperacetylates histones in tumor tissues.

PMID- 16001983
TI  - Cloning and functional characterization of the rabbit C-C chemokine receptor 2.
AB  - BACKGROUND: CC-family chemokine receptor 2 (CCR2) is implicated in the
      trafficking of blood-borne monocytes to sites of inflammation and is implicated
      in the pathogenesis of several inflammatory diseases such as rheumatoid
      arthritis, multiple sclerosis and atherosclerosis. The major challenge in the
      development of small molecule chemokine receptor antagonists is the lack of cross
      species activity to the receptor in the preclinical species. Rabbit models have
      been widely used to study the role of various inflammatory molecules in the
      development of inflammatory processes. Therefore, in this study, we report the
      cloning and characterization of rabbit CCR2. Data regarding the activity of the
      CCR2 antagonist will provide valuable tools to perform toxicology and efficacy
      studies in the rabbit model. RESULTS: Sequence alignment indicated that rabbit
      CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that
      rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2
      expressed as stable transfectants in U-937 cells binds radiolabeled 125I-mouse JE
      (murine MCP-1) with a calculated Kd of 0.1 nM. In competition binding assays,
      binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by
      human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1alpha or MIP-1beta. U
      937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human
      MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b.
      Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of
      125I-mouse JE (IC50 = 2.3 nM) to rabbit CCR2 and effectively blocks CCR2-mediated
      chemotaxis. CONCLUSION: In this study, we report the cloning of rabbit CCR2 and
      demonstrate that this receptor is a functional chemotactic receptor for MCP-1.

PMID- 16001984
TI  - Sodium channel Nav1.8 immunoreactivity in painful human dental pulp.
AB  - BACKGROUND: The tetrodotoxin-resistant voltage-gated sodium channel Nav1.8
      (SNS1/PN3) is expressed by nociceptors and may play a role in pain states.
      METHODS: Using specific antibodies for immunohistochemistry, we studied Nav1.8
      immunoreactivity in human dental pulp in relation to the neuronal marker
      neurofilament. Human tooth pulp was extracted from teeth harvested from a total
      of twenty-two patients (fourteen without dental pain, eight patients with dental
      pain). RESULTS: Fibres immunoreactive for Nav1.8, were significantly increased on
      image analysis in the painful group: median (range) Nav1.8 to Neurofilament %
      area ratio, non-painful 0.059 (0.006-0.24), painful 0.265 (0.13-0.5), P = 0.0019.
      CONCLUSION: Nav1.8 sodium channels may thus represent a therapeutic target in
      trigeminal nerve pain states.

PMID- 16001986
TI  - A new age now begins.

PMID- 16001989
TI  - Brain metastases in patients with breast cancer: new horizons.
AB  - Brain metastases occur in as many as one third of patients with disseminated
      breast cancer. In this article, we discuss various presentations of brain
      metastases from breast cancer and review evidence that supports different
      treatment options. Because no prospective, randomized, controlled studies, to our
      knowledge, have focused solely on patients with brain metastases from breast
      cancer, we will first review retrospective studies of patients with brain
      metastases from breast cancer. Randomized studies of patients with brain
      metastases caused by multiple primary cancers will also be examined, and the
      conclusions from these studies will be extrapolated to patients with breast
      cancer. Because brain metastases from breast cancer occur in a variety of
      different clinical settings, ranging from a single metastasis without extensive
      extracranial disease to multiple brain metastases with widespread extracranial
      disease, treatment approaches must be tailored to the specific circumstances of
      each patient. For different clinical scenarios, neurosurgical resection,
      radiosurgery, and/or whole-brain radiation therapy may be appropriate treatment
      options. For patients with brain metastases from breast cancer that overexpresses
      HER2/neu, trastuzumab could alter the natural history of the non-central nervous
      system (CNS) disease. Therefore, HER2 status could also influence the treatment
      of brain metastases from breast cancer. Given the prevalence of brain metastases
      in patients with metastatic breast cancer in contemporary series, the rationale
      for clinical trials of CNS screening and prophylactic cranial irradiation will be
      discussed.

PMID- 16001990
TI  - Efficacy and safety of intravenous bisphosphonates for patients with breast
      cancer metastatic to bone: a review of randomized, double-blind, phase III
      trials.
AB  - Intravenous bisphosphonates are the preferred treatment to prevent skeletal
      complications for patients with breast cancer and bone metastases. Pamidronate, a
      single-nitrogen bisphosphonate, was the early standard of care for such patients
      based on 2 large, placebo-controlled trials involving 754 patients. Zoledronic
      acid, a new-generation bisphosphonate containing 2 nitrogens, was evaluated in
      1130 patients with breast cancer in a large, randomized, comparative, phase III
      trial with pamidronate. At 25 months, zoledronic acid (4 mg) significantly
      reduced the overall risk of developing a skeletal-related event (SRE) by an
      additional 20% versus 90 mg pamidronate by multiple-event analysis. Furthermore,
      zoledronic acid was at least as effective as pamidronate in reducing the
      proportion of patients with > or = 1 SRE and in delaying the onset of SREs.
      Moreover, a retrospective subset analysis of 352 patients with > or = 1
      osteolytic lesion proved zoledronic acid more effective than pamidronate in
      reducing the risk and delaying the onset of SREs. Intravenous ibandronate (6 mg
      via 1-2-hour infusion) was evaluated in a placebo-controlled, phase III trial of
      466 patients and was significantly more effective than placebo in reducing the
      number of 12-week treatment periods in which an SRE occurred. The safety profiles
      among all intravenous bisphosphonates were similar; patients treated with
      intravenous bisphosphonates reported notably less bone pain but a higher
      incidence of mild to moderate transient infusion-related adverse events (eg,
      nausea, vomiting, myalgia, and anorexia) compared with placebo. In summary,
      intravenous bisphosphonates are effective for the treatment of bone metastases in
      patients with breast cancer and have similar safety profiles, but the shorter
      infusion time and greater efficacy of zoledronic acid in reducing overall
      skeletal morbidity provide advantages over other available agents.

PMID- 16001991
TI  - Weekly epoetin alfa during adjuvant chemotherapy for breast cancer: effect on
      hemoglobin levels and quality of life.
AB  - PURPOSE: Anemia, fatigue, and diminished quality of life (QOL) often are
      associated with chemotherapy. In a previous study of patients with early-stage
      breast cancer and a mean baseline hemoglobin (Hb) level of 12.1 g/dL, Hb
      decreased by 2.0 g/dL after 4 cycles of adjuvant chemotherapy. The current open
      label, nonrandomized, multicenter, prospective, community-based study evaluated
      the effects of 12-24 weeks of epoetin alfa (40,000 U subcutaneously once weekly
      initiated at the start of standard adjuvant chemotherapy) in patients with stage
      I-III breast cancer and baseline Hb levels > or =10 g/dL to < or =14 g/dL on Hb
      level, transfusions, and QOL. PATIENTS AND METHODS: Of 1792 patients enrolled,
      1785 were evaluable for safety and 1632 for efficacy. Mean age was 53 years +/-
      10.7 and mean baseline Hb level was 12.3 g/dL +/- 1.0. From baseline levels,
      epoetin alfa significantly increased Hb (1.3 g/dL +/- 1.5; P < 0.05) and improved
      QOL according to the Linear Analog Scale Assessment (LASA) of energy (5.1 mm +/-
      27.7), LASA activity (5.1 mm +/- 28.2), LASA overall QOL (4.3 mm +/- 26.7), and
      Functional Assessment of Cancer Therapy-Anemia (1.7 points +/- 14.0; P < 0.05 in
      each case). Patients with baseline mild anemia (Hb level >10 g/dL to < or =12
      g/dL) also had significant improvements from baseline levels in all 3 LASA
      parameters (P < 0.05). Epoetin alfa was well tolerated; clinically relevant
      thrombovascular events were reported in 4.3% of patients. RESULTS: In this study,
      epoetin alfa significantly improved Hb and QOL in mildly anemic patients with
      early-stage breast cancer receiving adjuvant chemotherapy. However, based on
      recent studies showing an increased risk of thrombovascular events in patients
      with cancer treated with erythropoietic agents beyond correction of anemia,
      treatment with epoetin alfa is not indicated or recommended in patients with
      cancer and Hb levels > 12 g/dL. CONCLUSION: Controlled studies are warranted to
      confirm the safety and efficacy of epoetin alfa therapy in patients with mild
      anemia receiving chemotherapy.

PMID- 16001992
TI  - Phase II study of pemetrexed in patients pretreated with an anthracycline, a
      taxane, and capecitabine for advanced breast cancer.
AB  - BACKGROUND: This phase II study evaluated the efficacy, safety, and health
      outcomes of pemetrexed treatment in heavily pretreated patients with advanced
      breast cancer. PATIENTS AND METHODS: Women with metastatic breast cancer,
      Karnofsky performance status > or = 70, and previous treatment with > or = 3
      regimens containing anthracyclines, taxanes, and capecitabine were eligible.
      Pemetrexed 500 mg/m2 intravenous infusion was administered on day 1 of a 21-day
      treatment cycle. RESULTS: Eighty patients were enrolled, and 60 received
      concurrent folic acid and vitamin B12 supplements per protocol amendment to
      minimize possible pemetrexed-related toxicity. The median numbers of cycles
      delivered were 3 for vitamin-supplemented patients and 2 for non-vitamin
      supplemented patients. Regardless of vitamin supplementation, the overall
      response rate was 8% (95% CI, 3%-16.6%), stable disease was exhibited in 36% of
      patients, median time to disease progression was 2.9 months, and median survival
      was 8.2 months. Improvements in patient-reported symptoms ranged from 16.2% for
      pain intensity to 32.1% for nausea. Major grade 3/4 toxicities were hematologic,
      with grade 4 neutropenia in 10% of patients and grade 3 toxicities consisting
      primarily of neutropenia (29%) and leukopenia (21%). There were no clear trends
      of the effect of supplementation on toxicity. CONCLUSION: Pemetrexed has modest
      antitumor activity and is well tolerated in heavily pretreated patients with
      breast cancer. Further evaluation of this multitargeted antifolate in advanced
      breast cancer is warranted.

PMID- 16001993
TI  - Pegylated liposomal doxorubicin and cyclophosphamide as first-line therapy for
      patients with metastatic or recurrent breast cancer.
AB  - PURPOSE: Pegylated liposomal doxorubicin (PLD) is an active agent for breast
      cancer. The efficacy and safety of PLD in combination with cyclophosphamide as
      first-line treatment of metastatic breast cancer (MBC) was evaluated in this
      phase II study. PATIENTS AND METHODS: Eligible patients had metastatic or
      recurrent breast cancer with no previous chemotherapy for metastatic disease.
      Patients were enrolled into 3 sequential cohorts: cohort I (n = 10) received PLD
      50 mg/m2 intravenously (I.V.) on day 1 and cyclophosphamide 100 mg/m2 orally on
      days 1-14 every 28-day cycle; cohort II (n = 20) received PLD 30 mg/m2 plus
      cyclophosphamide 600 mg/m2 I.V. on day 1 every 21 days; and cohort III (n = 21)
      received PLD 35 mg/m2 plus cyclophosphamide 600 mg/m2 I.V. on day 1 every 21
      days. RESULTS: An objective response was exhibited in 26 of 51 patients (4
      complete responses [CRs], 22 partial responses [PRs]; 51%) in the intent-to-treat
      population and responses were similar among cohorts. The clinical benefit rate
      (CR plus PR plus stable disease) was 86%. The median duration of response was
      35.1 weeks. The most common adverse events were nausea (71%), asthenia (69%), and
      neutropenia (67%). There was less toxicity in cohort II than in other cohorts. No
      clinical cardiac toxicity was observed. Only 2 of 20 patients in cohort II (10%)
      required treatment discontinuation as a result of adverse events. CONCLUSION:
      First-line combination therapy with PLD and cyclophosphamide is active and well
      tolerated in patients with MBC. The recommended doses from this study are PLD 30
      mg/m2 and cyclophosphamide 600 mg/m2 I.V. every 21 days.

PMID- 16001994
TI  - Gemcitabine/capecitabine in patients with metastatic breast cancer pretreated
      with anthracyclines and taxanes.
AB  - PURPOSE: Gemcitabine and capecitabine are 2 anticancer drugs with a mechanism of
      action involving metabolism of pyrimidine nucleotides. Both are among the few
      agents active in patients with metastatic breast cancer (MBC) progressing after
      therapy with anthracyclines and taxanes. We have conducted a phase II trial of
      gemcitabine/capecitabine in patients with disease progression after treatment
      with anthracyclines and taxanes. PATIENTS AND METHODS: Treatment included
      gemcitabine 2000 mg/m2 on day 1 every 3 weeks and capecitabine 2500 mg/m2 daily
      (divided into 2 doses) on days 1-14 every 3 weeks; treatment was administered
      until disease progression or unacceptable toxicity was documented. All patients
      received concomitant oral pyridoxine 300 mg twice daily to prevent hand-foot
      syndrome (HFS). Of 39 patients treated, 33 had received previous treatment with
      anthracyclines, 6 had medical contraindication to anthracyclines, 35 had
      previously received taxanes, and 23 had received vinorelbine. Fourteen patients
      had previous high-dose chemotherapy with stem cell rescue and 5 had previously
      received trastuzumab. Patients were 31-79 years of age (median, 55 years) and,
      altogether, were given 386 courses of therapy (range, 1-36 courses per patient;
      median, 6 courses). RESULTS: Grade 3/4 toxicities included HFS (11 courses, 6
      patients), stomatitis (6 courses, 2 patients), diarrhea (5 courses, 4 patients),
      anemia (5 courses, 2 patients), thrombocytopenia (5 courses, 2 patients), and
      neutropenia (1 course, 1 patient). Response rate (all 39 patients were evaluable)
      was 48.7% (partial response, n = 19; stable disease, n = 7; progressive disease,
      n = 13). Thirty-six patients died because of disease progression, and 3 are alive
      with progressive disease. Median follow-up was 26 months or until death. Median
      duration of response was 15 months (range, 3-26 months). Median time to disease
      progression was 5 months (range, 1-26 months). Median overall survival duration
      was 10 months (range, 1-37 months). CONCLUSION: In this cohort of patients
      heavily pretreated with anthracyclines and taxanes, the response rate to
      gemcitabine/capecitabine is encouraging, although response duration is limited.

PMID- 16001995
TI  - Final results of a phase II trial of preoperative TAC
      (docetaxel/doxorubicin/cyclophosphamide) in stage III breast cancer.
AB  - BACKGROUND: The use of preoperative chemotherapy for breast cancer has been
      demonstrated to result in similar disease-free survival (DFS) and overall
      survival (OS) as postoperative adjuvant chemotherapy. Additionally, the rate of
      pathologic complete response (pCR) in the breast after preoperative chemotherapy
      has been shown to correlate with survival. The objective of this study was to
      determine the pCR rate in patients with stage III breast cancer treated with 4
      cycles of TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500
      mg/m2) on day 1 before surgery. PATIENTS AND METHODS: From November 1998 through
      August 2001, we treated 40 patients (mean age, 47 years) with stage III breast
      cancer with TAC administered every 3 weeks for 4 cycles. RESULTS: We now report
      follow-up at 24 months. Responses were seen in 83% of patients, with 25%
      experiencing a clinical complete response, of which 4 patients (10%) had pCRs. At
      a follow-up of 2 years, data on DFS and OS are available on 37 patients: 12
      patients (38%) had disease progression, and 7 patients (21%) had died. Despite
      the use of prophylactic ciprofloxacin, some degree of myelosuppression was seen
      in all patients, with 24 patients (63%) experiencing grade 3/4 neutropenia.
      CONCLUSION: Based on the pCR rate seen in this trial, docetaxel given
      concomitantly with AC (doxorubicin/cyclophosphamide) for 4 cycles does not appear
      to be superior to 4 cycles of AC as preoperative treatment for stage III breast
      cancer. Based on other trials, longer durations of therapy and/or sequencing of
      AC and docetaxel may result in a higher pCR rate.

PMID- 16001996
TI  - Predictors of residual disease in repeat excisions for lumpectomies with margins
      less than 0.1 cm.
AB  - PURPOSE: This study sought to identify factors that would predict the presence of
      residual disease (RD) in repeat-excision specimens following an initial breast
      sparing excision procedure in which the margins of resection were free of tumor
      but in which tumor was very close to > or =1 margins. PATIENTS AND METHODS:
      Ninety-one lumpectomies with close but not transected margins and their
      subsequent repeat-excision specimens were analyzed for tumor type near margin in
      the primary excision, presence of RD, type of RD, stage of infiltrating carcinoma
      (IC) in the primary excision, extent of ductal carcinoma in situ (DCIS), and
      grade of IC and/or DCIS. RESULTS: Nineteen of 91 patients had DCIS only; 15 had
      IC only; and 57 had IC with DCIS in their primary excisions. Thirty-five cases
      (38%) contained RD in their subsequent repeat-excision specimens. Residual DCIS
      and/or IC was present in 58% of patients whose primary tumors were DCIS only or
      invasive carcinoma < 6 mm (T1a), whereas invasive carcinomas > or = 6 mm had RD
      in only 28%. Twenty-three patients (64%) with extensive DCIS had RD, whereas 12
      patients (22%) with no DCIS or minor DCIS (< 10 mm) had RD (chi2 = 16.27; P <
      0.001). Ductal carcinoma in situ was within 0.1 cm of the margin in 52 patients,
      and RD was present in 26 (50%), whereas 18 of 56 patients (32%) with IC close to
      the margin had RD (P < 0.05). Grade of DCIS and IC was not related to presence of
      RD. Residual carcinoma was present in 38% of repeat-excision specimens with close
      but not transected margins in this study. CONCLUSION: The extent of DCIS in the
      primary specimen, DCIS near > or = 1 margins, and size of infiltrating tumor were
      related to the presence of RD.

PMID- 16001997
TI  - Breast carcinoma metastatic to the bladder and renal pelvis requiring
      fulguration.
AB  - Breast cancer metastatic to the bladder has rarely been reported in the
      literature. A patient presented to our institution with pathologically confirmed
      breast cancer metastatic to the bladder with renal pelvis involvement as seen on
      retrograde pyelography. We believe cystoscopy with biopsy and fulguration to be
      the treatment of choice for breast cancer that has metastasized to the bladder
      because of the low rate of survival in patients with hematuria related to
      metastatic breast cancer.

PMID- 16001998
TI  - Volume replacement with polyglycolic acid mesh for correcting breast deformity
      after endoscopic conservative surgery.

PMID- 16001999
TI  - Targeted therapy in the macro mode.

PMID- 16002000
TI  - Breast cancer.

PMID- 16002001
TI  - Genomics-based prognosis and therapeutic prediction in breast cancer.
AB  - Breast cancer is a heterogeneous disease. DNA microarray technology is being
      applied to breast cancer to identify new prognostic biomarkers, to predict
      response to therapy, and to discover targets for the development of novel
      therapies. New diagnostic assays based on global gene expression are being
      introduced into clinical practice or tested in large-scale clinical trials. This
      review focuses on translational studies using microarray analyses and discusses
      best practice features and pitfalls. We note that factors that predict metastatic
      disease are not necessarily the same factors that predict therapeutic response.
      We believe that the characterization and discernment of different systems among
      breast cancers is crucial for understanding drug sensitivity and resistance
      mechanisms and for guiding therapy.

PMID- 16002002
TI  - Partial-breast radiation for early staged breast cancers: hypothesis, existing
      data, and a planned phase III trial.
AB  - This review of clinical data from partial-breast treatment studies discusses
      results from a single institution's experience using brachytherapy catheters, the
      MammoSite balloon (Proxima Company, Alpharetta, GA), and three-dimensional
      external beam partial-breast treatment. Rationale, techniques, dose schedules,
      and available results are presented. Intra-operative single-dose radiation to the
      lumpectomy site is also reviewed. The National Surgical Adjuvant Breast and Bowel
      Project (NSABP) and Radiation Therapy Oncology Group (RTOG) cooperative groups
      are opening a phase III trial to compare partial-breast treatment to the standard
      5- to 6-week course of whole-breast radiation. The design of this study is also
      presented in this review.

PMID- 16002003
TI  - Aromatase inhibitors in postmenopausal breast cancer patients.
AB  - Aromatase inhibitors (AIs) have greatly enriched the treatment of hormone
      receptor-positive breast cancer in postmenopausal patients. Before the
      introduction of the well-tolerated third-generation AIs, tamoxifen was the
      mainstay of endocrine therapy for hormone receptor-positive breast cancer. Many
      clinical trials have shown the superiority of AIs compared with tamoxifen in
      adjuvant breast cancer treatment, as well as their benefit in metastatic breast
      cancer. NCCN guidelines recommendations for their use are based on the evidence
      provided by these clinical trials. This discussion reviews the evidence
      supporting the current guidelines for use of AI therapy in the treatment of
      hormone receptor-positive postmenopausal breast cancer patients.

PMID- 16002004
TI  - Head and neck cancers.

PMID- 16002005
TI  - Induction chemotherapy for head and neck cancer: will history repeat itself?
AB  - Locally advanced squamous cell head and neck cancer remains a therapeutic
      challenge for multidisciplinary teams. Despite high objective response rates,
      induction chemotherapy has not resulted in tangible benefit in multiple
      randomized trials. In recent years, as most evidence solidified the role of
      concurrent chemotherapy and radiation as either primary or postoperative therapy
      for locally advanced head and neck cancer, induction chemotherapy fell out of
      scope and practice. The failure of older randomized trials to show a survival
      benefit from induction chemotherapy can be attributed to several factors. It is
      possible that the predominance of locoregional failure did not allow any added
      benefit from better systemic control to translate into a survival advantage.
      Alternatively, seemingly active chemotherapy regimens may have been suboptimal.
      Nevertheless, recent developments have altered our perception of head and neck
      cancer and its treatment. Locoregional control has dramatically improved with
      concurrent chemoradiotherapy. Of note is that none of the previously conducted
      randomized trials of induction chemotherapy used concurrent chemoradiotherapy in
      the control arm. Moreover, we witnessed the development of better combination
      regimens that improved efficacy in the induction setting. The previously standard
      cisplatin/5-fluoruracil (5-FU) combination is being replaced by the triple
      combination of taxane/ cisplatin/5-FU. Randomized trials showed that increased
      activity with the triplet regimen resulted in improved long-term disease control
      and survival. Finally, cetuximab, an active epidermal growth factor receptor
      inhibitor, is entering clinical practice and is expected to change the standard
      of therapy. With the emergence of more efficacious systemic therapies, the role
      of induction therapy warrants reevaluation. A number of randomized trials are
      planned or currently ongoing to investigate concurrent chemoradiotherapy with or
      without induction. These trials are anticipated to redefine the role of induction
      chemotherapy for head and neck cancer.

PMID- 16002006
TI  - Thyroid carcinoma.

PMID- 16002007
TI  - Surgical management of thyroid carcinoma.
AB  - Thyroid carcinoma has a unique biologic behavior characterized by early spread to
      regional lymph nodes and occasional extrathyroidal soft tissue extension but a
      low incidence of distant metastasis and infrequent disease-related death.
      Therefore, controversy exists over the proper extent of thyroidectomy and
      regional lymph node dissection in patients with differentiated thyroid carcinoma
      (DTC) and medullary thyroid carcinoma (MTC). The modest disease-specific
      mortality makes it unlikely that the extent of surgery will ever be the subject
      of a prospective randomized trial. Although more extensive cervical surgery may
      have only a limited effect on the duration of survival in patients with DTC, it
      may significantly improve quality of life by minimizing cervical recurrence. The
      high rates of cervical recurrence in patients with DTC and MTC have alerted
      physicians to the importance of fine-needle aspiration biopsy and ultrasonography
      for the diagnosis, preoperative staging, and follow-up of thyroid cancer. In
      patients with MTC, death caused by disease is uncommon in the absence of
      radiographically evident distant metastasis at the time of thyroidectomy.
      Cervical recurrence is even more common with MTC, and the need for compartment
      oriented lymphadenectomy is accepted as standard surgical treatment to minimize
      disease recurrence. Postoperatively, calcitonin (CT) levels can be used to guide
      clinical management, but basal CT levels should not be used to direct the timing
      of prophylactic thyroidectomy in affected high-risk patients with familial MTC.

PMID- 16002008
TI  - Microbial transformations of mercury: potentials, challenges, and achievements in
      controlling mercury toxicity in the environment.

PMID- 16002009
TI  - Interactions between nematodes and microorganisms: bridging ecological and
      molecular approaches.

PMID- 16002010
TI  - Biofilm development in bacteria.

PMID- 16002011
TI  - Microbial biogeochemistry of uranium mill tailings.

PMID- 16002012
TI  - Yeast modulation of wine flavor.

PMID- 16002013
TI  - Moving toward a systems biology approach to the study of fungal pathogenesis in
      the rice blast fungus Magnaporthe grisea.

PMID- 16002014
TI  - The biotrophic stages of oomycete-plant interactions.

PMID- 16002015
TI  - Contribution of nanosized bacteria to the total biomass and activity of a soil
      microbial community.

PMID- 16002016
TI  - Linkage of microbiology reports and hospital discharge diagnoses for surveillance
      of surgical site infections.
AB  - Surveillance of surgical site infections (SSIs) with feedback to surgical
      personnel is pivotal in decisions regarding infection control. Prospective
      surveillance is time and resource consuming, so we aimed to evaluate a method
      based on data collected routinely during care delivery. The study was carried out
      at three acute hospitals in North-eastern Italy, from 1 January 2001 to 31
      December 2001. Hospital discharge diagnoses (selected codes from the
      International Classification of Diseases, 9th Revision--Clinical Modification)
      and electronic microbiology reports (positive cultures from surgical wounds and
      drainages) were linked to identify suspected SSIs. A random sample of tracked
      events was submitted to total chart review in order to confirm the presence of
      SSIs retrospectively according to Centers for Disease Control and Prevention
      definitions. Of 865 suspected SSIs, 64.5% were identified from the
      microbiological database, 27.1% from discharge codes, and 8.4% from both. Four
      hundred and three admissions were sampled for review; the overall positive
      predictive value was 72% (95%CI=69-76%). Since inpatient individual antibiotic
      exposure is not registered in Italy, the combined use of discharge codes and
      microbiology reports represents the most feasible automated method for
      surveillance of SSIs developing during hospital stay.

PMID- 16002017
TI  - Reliability of assessment of adherence to an antimicrobial treatment guideline.
AB  - Assessment procedures for adherence to a guideline must be reliable and credible.
      The aim of this study was to explore the reliability of assessment of adherence,
      taking account of the professional backgrounds of the observers. A secondary
      analysis explored the impact of case characteristics on assessment. Six observers
      (two hospital pharmacists, two internists and two clinical microbiologists)
      assessed a random sample of 22 prescriptions made to infectious disease cases
      admitted to a department of internal medicine between February and August 2001.
      Agreement between observers with regard to adherence of these prescriptions to
      guideline recommendations concerning drug choice, duration of treatment, dosage
      and route of administration was measured using Cohen's kappa. Case
      characteristics were compared between cases where observers agreed and disagreed
      with two-sided Fisher's exact test. Agreement between all professionals was
      moderate for drug choice (0.59), fair for duration of therapy (0.36), moderate
      for dosage (0.48), and fair for route of administration (0.37). Agreement on drug
      choice was good within (0.75 and 0.83) and between (0.74) the internists and the
      hospital pharmacists, but was less within (0.31) the clinical microbiologists and
      between the clinical microbiologists and the internists (0.44) and the hospital
      pharmacists (0.42). Within the clinical microbiologists, agreement was good for
      dosage (0.79) and route of administration (0.66). There was frequent disagreement
      between observers regarding cases with combination therapy and non
      immunocompromised patients. Despite the small number of cases, our results
      suggest that internists and hospital pharmacists can reliably be used to assess
      adherence for drug choice. The level of agreement seems to be affected by
      combination therapy and the immune status of the patient.

PMID- 16002018
TI  - Follow-up of antibiotic prophylaxis: impact on compliance with guidelines and
      financial outcomes.
AB  - In order to enhance the quality of antibiotic use, a new financial system was
      introduced in Belgium in 1997, which links reimbursement of antibiotic costs
      incurred during prophylaxis in surgery and obstetrics to compliance with evidence
      based guidelines. At University Hospitals Leuven (UHL), this reimbursement scheme
      was supplemented with a follow-up programme in 2001 that informs physicians of
      their compliance with the guidelines and outlines the financial consequences of
      their use of prophylactic antibiotics. The aim of this paper is to evaluate the
      impact of the follow-up programme developed and implemented by a clinical
      pharmacist at UHL. The analysis drew on data on consumption and costs of
      antibiotics used in standard prophylaxis that were retrieved from patient
      invoices. Both financial outcomes and results on consumption patterns of
      antibiotics point to an increasing compliance with guidelines. An average annual
      loss of 92,353 Euro associated with prophylactic antibiotic use prior to the
      implementation of the follow-up programme evolved into a profit of 27,269 Euro
      following its introduction. The share of consumption of prophylactic antibiotics
      held by cefazolin and metronidazole, the two main antibiotics recommended by the
      guidelines, increased substantially or remained stable as a result of the follow
      up programme, whereas the shares held by other antibiotics generally fell.
      Moreover, the range of antibiotics consumed during standard prophylaxis narrowed.
      This follow-up programme thus reduced antibiotic costs, improved profitability
      and increased physician compliance with guidelines.

PMID- 16002019
TI  - Single-dose oral ciprofloxacin compared with single-dose intravenous cefazolin
      for prophylaxis in inguinal hernia repair: a controlled randomized clinical
      study.
AB  - The aim of this study was to compare the efficacy of single-dose intravenous
      cefazolin prophylaxis with single-dose oral ciprofloxacin prophylaxis in patients
      undergoing tension-free inguinal hernia repair with polypropylene mesh. In a
      prospective and randomized setting, 395 patients received either a single dose of
      500 mg of ciprofloxacin orally, 1--2h before the operation, or a single dose of
      1g cefazolin intravenously on induction of anaesthesia. The primary outcome was
      to determine the wound infection rate within one year. The overall infection
      among the entire study population was 2% (eight of 395) including 2% (four of
      199) of those receiving intravenous cefazolin and 2% (four of 196) of those
      treated with oral ciprofloxacin. There was no statistically significant
      difference between groups (P=0.59). All the infections were superficial
      incisional surgical site infections, and none progressed to a deep infection.
      Escherichia coli was the most commonly isolated bacterium. None of the infected
      patients developed recurrence of hernia. The rate of recurrence was 1.3% (five of
      395) at one year including 2% (four of 199) of those receiving cefazolin and 0.5%
      (one of 196) of those receiving ciprofloxacin. Oral ciprofloxacin prophylaxis was
      found to be an attractive option with its wide antibacterial spectrum, low cost
      and ease of administration in patients undergoing tension-free inguinal hernia
      repair with polypropylene mesh.

PMID- 16002020
TI  - Gold standard reduction of MRSA by silver?

PMID- 16002021
TI  - Reinforcement-based therapy: 12-month evaluation of an outpatient drug-free
      treatment for heroin abusers.
AB  - This controlled study examined the efficacy of reinforcement-based therapy (RBT)
      for producing enhanced abstinence outcomes over 12 months in opioid-dependent
      patients exiting a brief residential detoxification. Patients were randomly
      assigned upon completing their medically managed taper (i.e., detoxification) to
      RBT (N=66) or usual care (N=64) referral to community treatment programs. The 6
      month RBT program offered an array of abstinence-based incentives including rent
      payment for recovery housing, program-led recreational activities and skills
      training for procuring employment. RBT produced significantly higher self-report
      and urinalysis-confirmed rates of abstinence from opioids and cocaine relative to
      usual care at 1 (42% versus 15%) and 3 (38% versus 17%) months during treatment
      but not at 6 or 12 months after enrollment. The RBT but not the usual care group
      showed significant increases in the number of days worked and the amount of legal
      income earned at 3, 6 and 12 months. The results of this randomized study suggest
      that an intensive reinforcement-based therapy that includes abstinence-based
      recovery housing is a promising approach; however, further research is needed to
      determine the role of treatment intensity and the specific efficacy of RBT's
      component parts.

PMID- 16002022
TI  - The impact of a reduction in drug supply on demand for and compliance with
      treatment for drug dependence.
AB  - BACKGROUND: In early 2001, Australia experienced a sudden, dramatic and sustained
      decrease in heroin availability that was accompanied by sharp increases in price
      and decreases in street level purity--the so-called "heroin shortage". These
      unprecedented changes occurred in a context of widespread treatment availability,
      which made it possible for the first time to examine the impact of a sharp
      reduction in heroin supply in New South Wales (NSW) on entry to and adherence
      with treatment for heroin dependence. Given the evidence of drug substitution by
      some users, the current paper also examines the effects of the shortage on entry
      to treatment for other forms of drug dependence. METHODS: Interrupted time-series
      analysis of the number of persons entering opioid pharmacotherapy and other
      treatment modalities in NSW for heroin dependence and for the treatment for other
      types of drug dependence. FINDINGS: The heroin shortage was associated with a
      reduction in the number of younger persons entering opioid pharmacotherapy. There
      was a dramatic decrease in the number of persons entering heroin withdrawal or
      "assessment only" treatment episodes. There appear to have been small
      improvements in adherence to and retention in heroin treatment after the
      reduction in heroin supply. Relatively small increases were observed in numbers
      being treated for cocaine dependence. CONCLUSIONS: In the context of good
      treatment provision, a reduction in heroin supply appeared to produce modest
      improvements in intermediate outcomes. Supply and demand reduction measures, when
      both are implemented successfully, may be complementary.

PMID- 16002023
TI  - Mortality in heroin-assisted treatment in Switzerland 1994-2000.
AB  - BACKGROUND: A major goal of heroin-assisted treatment in Switzerland has been to
      reduce the drug-related mortality of heroin users. Therefore, a continuous
      monitoring of deaths under treatment is essential. AIMS: To assess mortality of
      participants in heroin-assisted treatment in Switzerland over a 7-year period
      from 1994 to 2000, and to compare this mortality to the general population and to
      other populations of opioid users, as reported in the literature. METHOD:
      Estimation of person years under heroin-assisted treatment from the complete case
      registry of heroin-assisted treatment in Switzerland. Estimation of standardized
      mortality ratios comparing the population in treatment to the Swiss population
      (standardized to the year 2000). RESULTS: Over the 7-year period, the crude death
      rate of patients in heroin-assisted treatment, and including one month after
      discharge from treatment, was 1% per year. The standardized mortality ratio for
      the entire observation period was 9.7 (95% C.I. 7.3-12.8), with females having
      higher standardized mortality ratios (SMR 17.2) than males (SMR 8.4). There was
      no clear time trend. CONCLUSION: Mortality in heroin-assisted treatment was low
      compared to the mortality rate of Swiss opioid users 1990s (estimated to be
      between 2.5 and 3%). It was also low compared to mortality rates of opioid users
      in other maintenance treatments in other countries as reported in the literature.
      The SMR was also lower than that reported in the only meta-analysis in the
      literature: 13.2 (95% C.I. 12.3-14.1). The low mortality rate is all the more
      noteworthy as heroin-assisted treatment in Switzerland included only refractory
      opioid addicts with existing severe somatic and/or mental problems. DECLARATION
      OF INTEREST: No conflicts of interest declared.

PMID- 16002024
TI  - Are judicial status hearings a "key component" of drug court? Six and twelve
      months outcomes.
AB  - Substantial evidence indicates that drug courts can be superior to traditional
      probation programs for enhancing treatment retention and reducing substance use
      and crime among drug offenders. Few studies have isolated the effects of the
      hypothesized "key components" of drug courts to determine their contributions to
      outcomes. This article presents outcomes at 6 and 12 months post-admission for
      misdemeanor drug court clients who were randomly assigned to different dosages of
      judicial status hearings. Although earlier work revealed superior during
      treatment effects for high-risk participants who were assigned to more frequent
      bi-weekly hearings, those effects did not extend post-treatment. The results did
      reveal significant pre-to-post improvements for participants, as a whole, in self
      reported drug use, alcohol use, and criminal recidivism; however, lacking a no
      drug court control condition, it is not possible to discern the magnitude of the
      effect of the drug court program. Approximately, half of the participants resumed
      drug or alcohol use within 12 months of admission to drug court, and
      approximately 10-15% resumed illegal activities. These findings lend credence to
      the potential effectiveness of drug courts; however, continuing-care strategies
      are required to extend the effects of drug courts beyond the initial active
      phases of the program.

PMID- 16002025
TI  - Efficacy of dose and contingency management procedures in LAAM-maintained cocaine
      dependent patients.
AB  - Opioid- and cocaine-dependent participants (N=140) were randomly assigned to one
      of the following in a 12-week clinical trial: LAAM (30, 30, 39 mg/MWF) with
      contingency management (CM) procedures (LC); LAAM (30, 30, 39 mg/MWF) without CM
      (LY); LAAM (100, 100, 130 mg/MWF) with CM (HC); LAAM (100, 100, 130 mg/MWF)
      without CM (HY). Urine samples were collected thrice-weekly. In CM, each urine
      negative for both opioids and cocaine resulted in a voucher worth a certain
      monetary value that increased for consecutively drug-free urines. Subjects not
      assigned to CM received vouchers according to a yoked schedule. Vouchers were
      exchanged for mutually agreed upon goods and services. Groups generally did not
      differ on retention and baseline characteristics. Overall opioid use was least in
      the HC and HY groups; opioid use decreased most rapidly over time in the HC group
      relative to the HY, LC and LY groups. Overall cocaine use was least in the HC
      group relative to the HY, LC, and LY groups; cocaine use decreased over time most
      rapidly in the HC and LY groups. Abstinence from both was greatest in the HC
      group. Opioid withdrawal symptoms decreased most rapidly in the high-dose groups
      relative to the low-dose groups. These results suggest that an efficacious
      maintenance dose is necessary for contingencies to be effective in facilitating
      both opioid and cocaine abstinence.

PMID- 16002026
TI  - Drug use practices among MDMA/ecstasy users in Ohio: a latent class analysis.
AB  - This study describes the drug use practices among 402 recent MDMA (3,4
      methelyenedioxymethamphetamine) users recruited in Ohio using respondent-driven
      sampling. About 64% of the participants were men, 81.6% were white, and the mean
      age was 20.9 years. Latent class analysis was used to identify subgroups of MDMA
      users. Use of cocaine, opioids, amphetamines, tranquilizers, inhalants,
      marijuana, and hallucinogens during the previous 6 months, and days of
      "drunkenness" in the past 30, were used for classification. A three-class model
      was preferable and reflected "Limited range," "Moderate range," and "Wide range"
      drug use patterns. For example, the conditional probability of using opioids
      during the previous 6 months was .07 in Class 1, .59 in Class 2, and .88 in Class
      3. Other substances followed similar patterns. Predictors of class membership
      were examined in a multinomial logit model in which the "Limited range" Class was
      treated as the reference group. Participants who were white, younger, and who
      reported more than 10 occasions of MDMA use were more likely to be in the "Wide
      range" drug use Class. Latent class analysis is a useful method to help describe
      and understand variability in polydrug use patterns.

PMID- 16002027
TI  - Circumstances of witnessed drug overdose in New York City: implications for
      intervention.
AB  - Drug users frequently witness the nonfatal and fatal drug overdoses of their
      peers, but often fail to intervene effectively to reduce morbidity and mortality.
      We assessed the circumstances of witnessed heroin-related overdoses in New York
      City (NYC) among a predominantly minority population of drug users. Among 1184
      heroin, crack, and cocaine users interviewed between November 2001 and February
      2004, 672 (56.8%) had witnessed at least one nonfatal or fatal heroin-related
      overdose. Of those, 444 (67.7%) reported that they or someone else present called
      for medical help for the overdose victim at the last witnessed overdose. In
      multivariable models, the respondent never having had an overdose her/himself and
      the witnessed overdose occurring in a public place were associated with the
      likelihood of calling for medical help. Fear of police response was the most
      commonly cited reason for not calling or delaying before calling for help
      (52.2%). Attempts to revive the overdose victim through physical stimulation
      (e.g., applying ice, causing pain) were reported by 59.7% of respondents, while
      first aid measures were attempted in only 11.9% of events. Efforts to equip drug
      users to manage overdoses effectively, including training in first aid and the
      provision of naloxone, and the reduction of police involvement at overdose events
      may have a substantial impact on overdose-related morbidity and mortality.

PMID- 16002028
TI  - Determinants of methadone treatment assignment among heroin addicts on first
      admission to public treatment centres in Italy.
AB  - AIMS: To identify factors associated with entering any methadone treatment at
      first admission at an NHS treatment centre in Italy and to investigate
      determinants of receiving detoxification or maintenance methadone treatments.
      METHODS: Data were analysed from 565 heroin addicts who entered for the first
      time one of 90 NHS treatment centres in 12 Italian regions between September 1998
      and March 2001. Subjects were interviewed at admission by the centre's staff and
      followed-up for 18 months. Details on treatments provided were recorded using a
      standardised form. Random effects logistic regression analysis was applied.
      RESULTS: Factors positively associated with any methadone treatment assignment
      were: being younger than 25 years and using heroin more than twice a day, having
      been recently incarcerated, and living with a partner. Independent predictors of
      admission to methadone maintenance were injecting heroin, having sex without a
      condom in the previous six months, being HIV positive and having been enrolled at
      a NHS TC where a psychiatrist was present. Using heroin once a day or more and
      using cocaine were factors associated with enrollment into detoxification
      treatment. A significant heterogeneity between centres was observed. CONCLUSIONS:
      Results from this study give an insight into different patient profiles who are
      enrolled in methadone treatments. The observed heterogeneity between centres
      indicates the need to develop and implement common guidelines for the access of
      heroin addicts to substitution treatment.

PMID- 16002029
TI  - fMRI response to spatial working memory in adolescents with comorbid marijuana
      and alcohol use disorders.
AB  - Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of
      concomitant use remains unclear. We previously demonstrated functional magnetic
      resonance imaging (fMRI) response to spatial working memory (SWM) among teens
      with alcohol use disorders (AUD) compared to controls, and predicted that
      adolescents with marijuana and alcohol use disorders would show additional
      abnormalities. Participants were three groups of 15-17-year-olds: 19 non-abusing
      controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid
      marijuana and alcohol use disorders (MAUD) and minimal other drug experience.
      After >2 days' abstinence, participants performed a SWM task during fMRI
      acquisition. fMRI brain response patterns differed between groups, despite
      similar performance on the task. MAUD youths showed less activation in inferior
      frontal and temporal regions than controls, and more response in other prefrontal
      regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and
      temporal activation, but more medial frontal response. Overall, MAUD youths
      showed different brain response abnormalities than teens with AUD alone, despite
      relatively short histories of substance involvement. This pattern could suggest
      compensation for marijuana-related attention and working memory deficits.
      However, relatively recent use and premorbid features may influence results, and
      should be examined in future studies.

PMID- 16002030
TI  - Transdermal nicotine alters some of marihuana's effects in male and female
      volunteers.
AB  - Despite the fact that tobacco and marihuana are often used together, relatively
      little is known about the effects of this combination. In order to investigate
      the effects of the principal psychoactive component in tobacco smoke, nicotine,
      on marihuana-induced intoxication, we conducted a double blind, cross-over
      experiment using nicotine transdermal patches. Ten male and 10 female
      participants received either placebo or a 21 mg transdermal nicotine patch 4 h
      before smoking one of two marihuana cigarettes (1.99 or 3.51% delta-9
      tetrahydrocannabinol (Delta(9) THC) content). Measurements of physiological
      activity (heart rate, blood pressure, and skin temperature) and subjective
      effects (self-reports of drug effects on visual analog scales (VAS) and the
      Addiction Research Center Inventory (ARCI)) were made periodically before and for
      3h after smoking. Nicotine pre-treatment enhanced several responses to marihuana,
      in particular, heart rate, reports of "stimulated" on the visual analog scales,
      and scores on the Amphetamine scale of the ARCI. Male participants reported a
      more pronounced effect of marihuana that persisted longer than that of the female
      participants. Compared to the male participants, female participants experienced
      an attenuated response to marihuana and were less affected by the drug
      combination. The results of this study show that nicotine can have an important
      influence on the subjective and physiological effects of smoked marihuana. These
      effects have implications for the safety and efficacy of marihuana smokers who
      are self-medicating with the nicotine transdermal patch to manage their tobacco
      dependence.

PMID- 16002031
TI  - Alcohol and benzodiazepines in falls: an epidemiological view.
AB  - Falls are common at all ages and especially in the elderly; it is important to
      understand contributing causes. Over a 1-year period we studied blood alcohol
      (BAC) and benzodiazepine concentrations in patients attending an emergency
      department because of a fall. The 22% of 615 patients tested were positive for
      alcohol, 55% were positive for benzodiazepines (BZD) and 1.5% were positive for
      both substances. A significantly larger proportion of males tested positive for
      alcohol (40.2%) than females (7.6%). Both in males and females the percentage as
      well as the extent of blood alcohol levels decreased significantly with age.
      Benzodiazepines were also consumed more frequently in males (8.5%) than in
      females (3.2%, p=0.007). Concerning BAC there was no difference between males
      (1.75+/-0.81 g/l) and females (1.66+/-0.91 g/l). In patients older than 70 years
      the BAC (1.30+/-0.80 g/l) was lower in comparison to younger ones. All blood
      samples positive for benzodiazepines could be traced back to diazepam
      consumption. We found a high number of young and middle aged patients using
      alcohol (males=49.7%; females=18.9%) and a lower but still relevant number of
      benzodiazepine users (males=9.5%; females=2.4%). In addition, this study shows
      that alcohol plays a more important role in patients up to 70 years in fall
      related accidents when compared to accidents of other causes.

PMID- 16002032
TI  - Prediction of relapse to frequent heroin use and the role of methadone
      prescription: an analysis of the Amsterdam Cohort Study among drug users.
AB  - The risk of relapse into frequent heroin use was studied among 732 participants
      of the Amsterdam Cohort Study (ACS) on HIV/AIDS among drug users, who experienced
      an episode of abstinence from or occasional use of heroin. Participants of the
      ACS were recruited primarily from easy access ("low-threshold") methadone
      programs. The duration of abstinence/occasional use and relative risks (RR) of
      relapse were estimated by analyzing 1577 episodes by means of survival analysis
      using characteristics of patients and methadone treatment as covariates. The
      majority of episodes (85.8%) were followed by relapse within 5 years. Less
      education, intense use of heroin prior to the episode of abstinence or well
      controlled use, occasional use of heroin and intense use of cocaine during the
      episode, and having a drug-using partner or having no partner were significantly
      associated with a higher risk of relapse. Among frequent attendees of a "low
      threshold" methadone program, relapse was associated with the daily dose of
      methadone: RR for dosages <40 and 40-60 mg, compared with doses of >100mg, were
      1.45 (P<0.01) and 1.59 (P<0.01), respectively. No beneficial influence was
      revealed of methadone dosage or program attendance in itself on the risk of
      relapse into cocaine. High doses of methadone in a harm-reduction setting extend
      the duration of an episode of no or occasional use of heroin. Other factors, such
      as no occasional use of heroin during the episode, no use of cocaine, and having
      a non-using partner, seem to be equally important.

PMID- 16002033
TI  - Telephone self-monitoring among alcohol use disorder patients in early recovery:
      a randomized study of feasibility and measurement reactivity.
AB  - Frequent symptom self-monitoring protocols have become popular tools in the
      addiction field. Interactive Voice Response (IVR) is a telephone monitoring
      system that has been shown to be feasible for collecting frequent self-reports
      from a variety of research populations. Little is known, however, about the
      feasibility of using IVR monitoring in clinical samples, and few controlled
      trials exist assessing the impact of any type of frequent self-report monitoring
      on the behaviors monitored. This pilot study with patients in early recovery from
      an alcohol use disorder (n=98) evaluated compliance with two IVR monitoring
      protocols, subjective experiences with monitoring, and change in symptoms
      associated with monitoring (i.e., measurement reactivity). Participants were
      randomly assigned to call an IVR system daily for 28 days, once per week for 4
      weeks, or only to complete 28-day follow-up assessment including retrospective
      drinking reports. Monitoring calls assessed alcohol craving, substance use,
      emotional well-being, and PTSD symptoms. Most monitoring participants completed
      calls on at least 75% of scheduled days (72.2% and 59.2% for daily and weekly,
      respectively). Including reconstructed data from follow-up of missed calls
      yielded 77.8% and 74.1% of maximum data points, respectively. Most monitoring
      participants indicated the protocol was manageable and reported positive or no
      effects of monitoring on urges to use alcohol, actual drinking, and PTSD
      symptoms. Analyses of measurement reactivity based on assessment one month after
      randomization found no significant group differences on drinking, craving for
      alcohol, or PTSD-related symptoms. Results suggest that IVR technology is
      feasible and appropriate for telephone symptom monitoring in similar clinical
      samples.

PMID- 16002034
TI  - Alcohol use and HIV risk behaviors among HIV-infected hospitalized patients in
      St. Petersburg, Russia.
AB  - PURPOSE: Russia has high per capita alcohol consumption and an injection-drug-use
      driven HIV epidemic. However, the role of alcohol in the spread of HIV infection
      in Russia is largely unexplored. Thus, we assessed recent alcohol use and
      associated HIV risk behaviors among HIV-infected persons in St. Petersburg,
      Russia. METHODS: We recruited HIV-infected hospitalized patients from the Botkin
      Infectious Disease Hospital between June 2001 and March 2002. Interviewers
      assessed alcohol and drug use with the addiction severity index (ASI) and sex-
      and drug-risk behaviors with the risk assessment battery (RAB). Lifetime abuse or
      dependence diagnoses for alcohol and drugs were established by a physician with
      addiction medicine training. RESULTS: Among 201 subjects, diagnoses of abuse or
      dependence (AB/DEP) were common: 9% (19/201) had only alcohol AB/DEP; 39%
      (78/201) had alcohol and drug AB/DEP; 47% (95/201) had only drug AB/DEP; and 4%
      (9/201) had no diagnosis of alcohol or drug AB/DEP. Sex- and drug-risk behaviors
      varied significantly by substance use diagnosis. Subjects with any alcohol AB/DEP
      had higher sex-risk RAB scores than those with drug only AB/DEP (6.1 versus 3.9,
      p<.0001). Among subjects with any diagnosis of drug AB/DEP, having in addition an
      alcohol diagnosis was associated with unclean needle use in the last six months
      (33% (26/78) versus 21% (20/95), p=0.08). CONCLUSIONS: Lifetime alcohol diagnoses
      of abuse or dependence were present in nearly one-half of hospitalized HIV
      infected patients in St. Petersburg, Russia and were associated with
      significantly higher sex-risk behaviors and borderline significantly higher drug
      risk behaviors. As HIV infection spreads rapidly in Russia and Eastern Europe,
      these data support the need for HIV risk-reduction interventions in alcohol
      abusing populations and raise the potential of benefit by addressing alcohol use
      in HIV-infected populations.

PMID- 16002035
TI  - An evaluation of the reinforcing effects of memantine in cocaine-dependent
      humans.
AB  - The purpose of this double-blind, outpatient study was to evaluate the
      reinforcing and subjective effects of the uncompetitive N-methyl-d-aspartate
      (NMDA) antagonist memantine in cocaine-dependent humans. Eight participants (two
      females, six males) completed this study which consisted of three blocks of seven
      sessions; each block tested a different dose of memantine. During the first two
      sessions of each block, participants "sampled" the memantine capsule (10, 20, or
      30 mg) and the placebo capsule that were available for the next five sessions.
      During the five subsequent sessions, participants had an opportunity to self
      administer either the active or placebo capsule. Memantine was not reinforcing
      and subjective-effects ratings were not altered as a function of dose. Results
      suggest that these doses of memantine do not have abuse liability in cocaine
      dependent individuals.

PMID- 16002036
TI  - Relationship between blood alcohol concentration and carbohydrate-deficient
      transferrin among drivers.
AB  - Carbohydrate-deficient transferrin (CDT) was quantified in 408 blood specimens,
      randomly selected from 1260 drivers apprehended and submitted to blood alcohol
      concentration (BAC) determination. The first step of the study was to observe
      whether a BAC based pre-evaluation was relevant for deciding to test drivers for
      chronic alcohol abuse. For this purpose, the diagnosis of chronic alcohol abuse
      was verified by CDT quantification, with a voluntary high positive cut-off fixed
      at 3% for high specificity. The results display a significant increase in the
      part of chronic alcohol abusers with respect to increasing BAC: a few alcohol
      abusers were present in the BAC category below 0.5 g/L, and their frequency
      increased to 47 and 67% when BAC was between 3 and 3.5 g/L and above 3.5 g/L,
      respectively. Secondly, the usefulness of the biomarker CDT in the traffic safety
      context was investigated by observing whether drivers with abnormally increased
      CDT value had also higher BAC. The average BAC was 1.32 g/L in drivers with CDT
      below 1%, and increased to 2.28 g/L in drivers with CDT above 3%. Statistical
      analysis showed evidence of a monotone increasing link between BAC and CDT
      (P<0.0001). We confirmed here the relevance of BAC-based pre-evaluation before
      testing chronic alcohol abuse among drivers, and demonstrated that CDT is a
      biomarker suitable for traffic safety context, as drivers with increased CDT had
      significantly higher BAC.

PMID- 16002037
TI  - Contingency management treatments that reinforce completion of goal-related
      activities: participation in family activities and its association with outcomes.
AB  - Contingency management (CM) techniques that reinforce completion of nondrug
      related activities may be efficacious in treating substance dependence. No
      studies to date have evaluated whether involvement in particular types of
      activities reduces problems in those domains. One hundred fifty-nine cocaine
      abusing adults who had been randomized to a CM intervention were categorized
      based on whether or not they engaged in three or more family related activities
      during the 12-week treatment period. Differences between the groups were
      evaluated with respect to treatment retention, length of continuous abstinence,
      and changes from baseline to the end of the intervention in ASI-family scores and
      days of family conflict. Participants who engaged in family activities (N=29)
      remained in treatment longer, were abstinent for more weeks, and reported greater
      reduction in family conflict compared to participants who did not engage in
      family activities (N=130). These data suggest that participants who elect to
      complete family related activities during CM treatments may evidence improved
      outcomes and reduced family conflict.

PMID- 16002038
TI  - In vivo chloroquine resistance and prevalence of the pfcrt codon 76 mutation in
      Plasmodium falciparum isolates from the Republic of Congo.
AB  - Chloroquine (CQ) resistance in Plasmodium falciparum has been particularly
      associated with mutations in the pfcrt gene. The present study was carried out in
      the malaria hyperendemic town of Brazzaville (Republic of Congo, Central Africa)
      where CQ is still recommended and used as a first-line drug for P. falciparum
      malaria. We assessed the efficacy of CQ in vivo, and the association between
      pfcrt mutation at codon 76 and treatment outcome in 50 children with
      uncomplicated malaria. The failure rate on day 28 was 95.7% and the pfcrt K76T
      mutation was present in 100% of isolates. No variation in the multiplicity of
      infection was observed in pre- and post-treatment isolates. In further 87
      isolates from uncomplicated patients not treated with CQ, the mutation was
      detected in 98.5% of isolates. This study confirms the high level of in vivo
      resistance to CQ and shows the high prevalence of pfcrt K76T mutation in the
      Republic of Congo.

PMID- 16002039
TI  - Plasmodium falciparum malaria in south-west Nigerian children: is the
      polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity
      of malaria?
AB  - Plasmodium falciparum malaria remains a major public health hazard in sub-Saharan
      African children. While the factors that determine the variations in clinical
      outcome of a malaria have not been completely defined, both host and parasite
      factors, as well as the complex molecular interactions between them have been
      implicated. The cyto-adherent properties of the P. falciparum-infected red blood
      cells are considered as key properties in the pathogenesis of malaria and the
      polymorphisms of the host adhesion molecules could contribute to the severity of
      malaria. Clinical information and blood samples were collected from 223 children
      from Ibadan (south-west Nigeria), median age of 34.5 months, presenting with
      different clinical manifestations of malaria--clinically asymptomatic parasitism
      (ACP), acute uncomplicated malaria (UM) and severe malaria (SM)--as defined by
      WHO criteria. The polymorphisms of genes coding for four human adhesion molecules
      at six different loci (ICAM-1 exons 2, 4 and 6, E-selectin exon 2, CD36 exon 10,
      and PECAM exon 3) were studied. DNA samples were prepared for further genotyping
      of the six exons mentioned above by PCR-RFLPs using the appropriate restriction
      digests for each loci. The ICAM-1 exon 4 locus was monomorphic. All the other
      loci were at Hardy-Weinberg equilibrium (HWE). The E-selectin locus had very low
      heterozygosity (approximately 0.06) in contrast to the other loci under study
      (0.23-0.44). Once the data was further processed for covariates (age and parasite
      density) and taking as the reference category the ACP group, results show that in
      the presence of the G allele at the ICAM-1 exon 6 there is an increased risk (3.6
      times) of severe malaria. As far as the T allele in the E-selectin exon is
      concerned, the number of sampled DNAs with the T allele within both the UM and SM
      categories is too low for drawing any relevant conclusion at this stage. In
      conclusion, these results suggest that genetic polymorphisms at host adhesion
      molecules loci are an important variable in the susceptibility to severe malaria.
      Further studies of host loci are needed to further delineate which polymorphisms
      are associated with severe malaria and increase our knowledge of the biology of
      host-parasite interactions.

PMID- 16002040
TI  - Improved survival of very high light and oxidative stress is conferred by
      spontaneous gain-of-function mutations in Chlamydomonas.
AB  - Investigations into high light and oxidative stress in photosynthetic organisms
      have focussed primarily on genetic impairment of different photoprotective
      functions. There are few reports of "gain-of-function" mutations that provide
      enhanced resistance to high light and/or oxidative stress without reduced
      productivity. We have isolated at least four such very high light resistant
      (VHL(R)) mutations in the green alga, Chlamydomonas reinhardtii, that permit near
      maximal growth rates at light intensities lethal to wild type. This resistance is
      not due to an alteration in electron transport rate or quantity and functionality
      of the two photosystems that could have enhanced photochemical quenching. Nor is
      it due to reduced excitation pressure by downregulation of the light harvesting
      antennae or increased nonphotochemical quenching. In fact, photosynthetic
      activity is unaffected in more than 30 VHL(R) isolates. Instead, the basis of the
      VHL(R) phenotype is a combination of traits, which appears to be dominated by
      enhanced capacity to tolerate reactive oxygen species generated by excess light,
      methylviologen, rose bengal or hydrogen peroxide. This is further evidenced in
      lower levels of ROS after exposure to very high light in the VHL(R)-S9 mutant.
      Additionally, the VHL(R) phenotype is associated with increased zeaxanthin
      accumulation, maintenance of fast synthesis and degradation rates of the D1
      protein, and sustained balanced electron flow into and out of PSI under very high
      light. We conclude that the VHL(R) mutations arose from a selection pressure that
      favors changes to the regulatory system(s) that coordinates several
      photoprotective processes amongst which repair of PSII and enhanced
      detoxification of reactive oxygen species play seminal roles.

PMID- 16002041
TI  - Interaction of the N-terminal segment of pulmonary surfactant protein SP-C with
      interfacial phospholipid films.
AB  - Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a
      hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine
      containing N-terminal segment. This segment is likely the only structural motif
      the protein projects out of the bilayer in which SP-C is inserted and is
      therefore a candidate motif to participate in interactions with other bilayers or
      monolayers. In the present work, we have detected intrinsic ability of a peptide
      based on the sequence of the N-terminal segment of SP-C to interact and insert
      spontaneously into preformed zwitterionic or anionic phospholipid monolayers. The
      peptide expands the pi-A compression isotherms of interfacial
      phospholipid/peptide films, and perturbs the lipid packing of phospholipid films
      during compression-driven liquid-expanded to liquid-condensed lateral
      transitions, as observed by epifluorescence microscopy. These results demonstrate
      that the sequence of the SP-C N-terminal region has intrinsic ability to interact
      with, insert into, and perturb the structure of zwitterionic and anionic
      phospholipid films, even in the absence of the palmitic chains attached to this
      segment in the native protein. This effect has been related with the ability of
      SP-C to facilitate reinsertion of surface active lipid molecules into the lung
      interface during respiratory compression-expansion cycling.

PMID- 16002042
TI  - The association between heroin use and anxiety sensitivity among inner-city
      individuals in residential drug use treatment.
AB  - The current study represents an initial investigation of the association between
      heroin use and anxiety sensitivity (AS). Within a sample of 172 inner-city
      treatment seeking drug users, AS was compared across past year (1) heroin users
      with no crack/cocaine use (n=12); (2) crack/cocaine users with no heroin use
      (n=66); (3) users of both heroin and crack/cocaine (n=45); and (4) individuals
      with no use of heroin or crack/cocaine (n=49). Consistent with expectations,
      primary heroin users evidenced higher levels of AS than all other groups, with
      these differences also evidenced for the physical and social subscales.
      Differences in AS total score and physical subscale score persisted after
      controlling for demographic variables, depressive symptoms, and primary use of
      drugs other than heroin and crack/cocaine including alcohol, nicotine, marijuana,
      and hallucinogens. Findings suggest a unique relationship between AS and heroin,
      and set the stage for future work explicating the direction of the observed
      association.

PMID- 16002043
TI  - Poly(ADP-ribose)polymerase-1 is required for integration of the human
      immunodeficiency virus type 1 genome near centromeric alphoid DNA in human and
      murine cells.
AB  - This study examined the efficiency of human immunodeficiency virus type 1 (HIV-1)
      integration in poly(ADP-ribose)polymerase-1 (PARP-1)-deficient murine cells and
      in human cell lines transfected with small interfering RNA against PARP-1 (PARP-1
      siRNA). To semi-quantify the amount of integrated HIV-1 genome, real-time nested
      PCR was carried out using primers specific for Alu and alphoid DNA combined with
      primers for the HIV-1 genome. The results showed that the integration efficiency
      of the HIV-1 genome near Alu DNA, which is randomly distributed in the
      chromosome, is reduced in PARP-1-deficient murine cells, but not in PARP-1 siRNA
      transfected human cells. By contrast, the integration efficiency of the HIV-1
      genome near alphoid DNA, which is localized in the centromere region, is
      significantly reduced in PARP-1-deficient murine cells and in PARP-1 siRNA
      transfected human cells. These results suggest that PARP-1 is required for HIV-1
      integration near the centromere region both in human and murine cells.

PMID- 16002044
TI  - Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding.
AB  - CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an
      extracellular matrix glycosaminoglycan, in a tightly regulated manner. This
      regulated interaction has been implicated in inflammation and tumor metastasis.
      CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due
      to alternative splicing. Here, we identify serine 180 in human CD44H as the site
      of chondroitin sulfate addition and show that lack of chondroitin sulfate
      addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin
      fusion protein expressed in HEK293 cells, and CD44H expressed in murine L
      fibroblast cells were modified by chondroitin sulfate, as determined by reduced
      sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180
      or glycine 181 in CD44H reduced chondroitin sulfate addition and increased
      hyaluronan binding, indicating that serine 180 is the site for chondroitin
      sulfate addition in CD44H and that this negatively regulates hyaluronan binding.

PMID- 16002045
TI  - Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin
      complex.
AB  - Ionizing radiation induces the production of reactive oxygen species, which play
      an important causative role in apoptotic cell death. Therefore, compounds that
      scavenge reactive oxygen species may confer regulatory effects on apoptosis.
      Superoxide dismutase (SOD) mimetics have been shown to be protective against cell
      injury caused by reactive oxygen species. We investigated the effects of the
      manganese (III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable
      SOD mimetic, on ionizing radiation-induced apoptosis. Upon exposure to 2 Gy of
      gamma-irradiation, there was a distinct difference between the control cells and
      the cells pre-treated with 5 microM MnTMPyP for 2 h with regard to apoptotic
      parameters, cellular redox status, mitochondria function, and oxidative damage to
      cells. MnTMPyP effectively suppressed morphological evidence of apoptosis and DNA
      fragmentation in U937 cells exposed to ionizing radiation. The [GSSG]/[GSH+GSSG]
      ratio and the generation of intracellular reactive oxygen species were higher and
      the [NADPH]/[NADP(+)+NADPH] ratio was lower in control cells compared to MnTMPyP
      treated cells. The ionizing radiation-induced mitochondrial damage reflected by
      the altered mitochondrial permeability transition, the increase in the
      accumulation of reactive oxygen species, and the reduction of ATP production were
      significantly higher in control cells compared to MnTMPyP-treated cells. MnTMPyP
      pre-treated cells showed significant inhibition of apoptotic features such as
      activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl
      2 compared to control cells upon exposure to ionizing radiation. This study
      indicates that MnTMPyP may play an important role in regulating the apoptosis
      induced by ionizing radiation presumably through scavenging of reactive oxygen
      species.

PMID- 16002046
TI  - Vascular endothelial growth factor impairs the functional ability of dendritic
      cells through Id pathways.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that plays an
      important role in tumor growth and progression. Recent evidence suggests an
      alternate, albeit indirect, role of VEGF on host immune response to tumors. VEGF
      appears to diminish host immunity by altering the function of major antigen
      presenting cells such as dendritic cells (DCs) [D.I. Gabrilovich, T. Ishida, S.
      Nadaf, J.E. Ohm, D.P. Carbone, Antibodies to vascular endothelial growth factor
      enhance the efficacy of cancer immunotherapy by improving endogenous dendritic
      cell function, Clin. Cancer Res. 5 (1999) 2963-2970, D. Gabrilovich, T. Ishida,
      T. Oyama, S. Ran, V. Kravtsov, S. Nadaf, D.P. Carbone, Vascular endothelial
      growth factor inhibits the development of dendritic cells and dramatically
      affects the differentiation of multiple hematopoietic lineages in vivo, Blood 92
      (1998) 4150-4166, T. Oyama, S. Ran, T. Ishida, S. Nadaf, L. Kerr, D.P. Carbone,
      D.I. Gabrilovich, Vascular endothelial growth factor affects dendritic cell
      maturation through the inhibition of nuclear factor-kappa B activation in
      hemopoietic progenitor cells, J. Immunol. 160 (1998) 1224-1232.]. DCs are prime
      initiators of host immunity as they are known to activate both primary as well as
      secondary immune responses [J. Banchereau, F. Briere, C. Caux, J. Davoust, S.
      Lebecque, Y.J. Liu, B. Pulendran, K. Palucka, Immunobiology of dendritic cells,
      Ann. Rev. Immunol. 18 (2000) 767-811.]. However, the exact nature of how VEGF
      suppresses DC function is not fully clear. In this report, we show that DCs
      cultured in the presence of VEGF are less potent in stimulating antigen-specific
      T-cells. Furthermore, by using DCs derived from Id1(-/-) mice that are defective
      in Flt-1 signaling, we demonstrated that the inhibitory function of VEGF on DC
      function is most likely mediated by Flt-1. Thus, the role of VEGF in
      downregulating host immunity may highlight a unique role of VEGF in the
      pathogenesis of cancer.

PMID- 16002047
TI  - Expression of the multifunctional Y-box protein, YB-1, in myofibroblasts of the
      infarcted rat heart.
AB  - Intracellular signaling mechanisms regulating the turnover of alpha-SMA-positive
      myofibroblasts (myoFbs) at the site of myocardial infarction (MI) are poorly
      understood. Y-Box (YB)-1, a multifunctional protein, may be involved in
      regulation of proliferation, migration and apoptosis of myoFbs. Our objective was
      to study the expression of YB-1 in the infarcted rat heart and its localization
      in myoFbs. On days 3-28 following MI, we monitored YB-1 expression and its
      colocalization with alpha-SMA, and proliferation markers PCNA and Ki-67 in
      infarcted tissue by Western blot, immunohistochemistry, and immunofluorescent
      double-labeling. YB-1 is barely detectable in normal myocardium. At the infarct
      site, however, YB-1 is markedly elevated from day 3 post-MI concomitant with the
      induction of cell proliferation. MyoFbs are the major source of YB-1 and retain
      it up to day 28 post-MI. We suggest early expression of YB-1 promotes
      proliferation and migration of myoFbs, whereas prolonged expression may be
      responsible for scar formation.

PMID- 16002048
TI  - Determination of the dissociation constants for recombinant c-Myc, Max, and DNA
      complexes: the inhibitory effect of linoleic acid on the DNA-binding step.
AB  - c-Myc, the protein product of protooncogene c-myc, functions in cell
      proliferation, differentiation, and neoplastic disease. In this study,
      recombinant c-Myc and Max proteins, encompassing DNA binding (basic region) and
      dimerization (helix-loop-helix/leucine zipper) domain of human origin, were
      expressed in bacteria as Myc87 and Max85. Myc87 was purified under denatured
      conditions and was renatured again. The dissociation constant for the protein
      dimers and for dimer/DNA complexes were not detectable by isothermal titration
      calorimetry because of the low degree of solubility of Myc87 and Max85.
      Therefore, we set up equations which were used to determine the dissociation
      constants from the proportion of protein-DNA complexes. The dimer dissociation
      constants in TBS were 5.90(+/-0.54)x10(-7)M for Max85/Max85 homodimer, 6.85(+/
      0.25)x10(-3)M for Myc87/Myc87 homodimer, and 2.55(+/-0.29)x10(-8)M for
      Myc87/Max85 heterodimer, and the DNA-binding dissociation constants in TBS were
      1.33(+/-0.21)x10(-9)M for Max85/Max85/DNA, 2.27(+/-0.08)x10(-12)M for
      Myc87/Myc87/DNA, and 4.43(+/-0.37)x10(-10)M for Myc87/Max85/DNA. In addition, we
      revealed that linoleic acid which is known as an inhibitor for the formation of
      Max/Max/DNA complex reduced the affinity of Max homodimer for DNA. This result
      indicates that linoleic acid may bind to the DNA-binding region of Max homodimer.

PMID- 16002049
TI  - Using optimized evidence-theoretic K-nearest neighbor classifier and pseudo-amino
      acid composition to predict membrane protein types.
AB  - Knowledge of membrane protein type often provides crucial hints toward
      determining the function of an uncharacterized membrane protein. With the
      avalanche of new protein sequences emerging during the post-genomic era, it is
      highly desirable to develop an automated method that can serve as a high
      throughput tool in identifying the types of newly found membrane proteins
      according to their primary sequences, so as to timely make the relevant
      annotations on them for the reference usage in both basic research and drug
      discovery. Based on the concept of pseudo-amino acid composition [K.C. Chou,
      Proteins: Struct. Funct. Genet. 43 (2001) 246-255; Erratum: Proteins: Struct.
      Funct. Genet. 44 (2001) 60] that has made it possible to incorporate a
      considerable amount of sequence-order effects by representing a protein sample in
      terms of a set of discrete numbers, a novel predictor, the so-called "optimized
      evidence-theoretic K-nearest neighbor" or "OET-KNN" classifier, was proposed. It
      was demonstrated via the self-consistency test, jackknife test, and independent
      dataset test that the new predictor, compared with many previous ones, yielded
      higher success rates in most cases. The new predictor can also be used to improve
      the prediction quality for, among many other protein attributes, structural
      class, subcellular localization, enzyme family class, and G-protein coupled
      receptor type. The OET-KNN classifier will be available as a web-server at
      http://www.pami.sjtu.edu.cn/kcchou.

PMID- 16002050
TI  - Transport of dietary phenethyl isothiocyanate is mediated by multidrug resistance
      protein 2 but not P-glycoprotein.
AB  - We demonstrated recently that phenethyl isothiocyanate (PEITC), a potent
      anticarcinogen present in cruciferous vegetables, inhibited P-glycoprotein (P-gp)
      and multidrug resistance protein 1 (MRP1) and that MRP1 can transport PEITC
      and/or its metabolites. In this study, we have examined whether PEITC is
      transported by P-gp and MRP2, two transporters with high expression in human
      intestine, liver and kidney. Using (14)C-PEITC, no significant difference was
      observed for the intracellular accumulation of PEITC in human breast cancer MCF
      7/sensitive (control) and MCF-7/ADR (P-gp overexpressing) cells at PEITC
      concentrations of 1, 10 and 50 microM. Moreover, the presence of verapamil or
      PSC833, two P-gp inhibitors, had no significant effect on the intracellular
      accumulation of PEITC in P-gp overexpressing MCF-7/ADR and MDA435/LCC6MDR1 cells,
      indicating that PEITC may not be a substrate for P-gp. In contrast, (14)C-PEITC
      intracellular accumulation in the kidney epithelial MDCK II/MRP2 cells
      (transfected with human MRP2) was significantly lower than in the wild-type MDCK
      II/wt cells at PEITC concentrations of 1, 5, 10 and 50 microM. The presence of
      MK571, an MRP inhibitor, significantly enhanced (14)C-PEITC accumulation in MDCK
      II/MRP2 but not MDCK II/wt cells. Furthermore, depletion of intracellular
      glutathione (GSH) following treatment with buthionine sulphoximine, an inhibitor
      of GSH biosynthesis, significantly increased (14)C-PEITC intracellular
      accumulation in a concentration-dependent manner. Transcellular transport studies
      also demonstrated that depletion of intracellular GSH reduced the mean ratio of
      basal-to-apical transport to apical-to-basal transport of PEITC in MDCK II/MRP2,
      but not MDCK II/wt cell monolayers. These results indicate that GSH plays an
      important role in the MRP2-mediated transport of PEITC. The findings provide new
      information concerning the interactions between PEITC and membrane transporters
      and suggest the possibility of PEITC interactions with xenobiotics that are MRP2
      substrates.

PMID- 16002051
TI  - The relationship between the anti-inflammatory effects of curcumin and cellular
      glutathione content in myelomonocytic cells.
AB  - Oxidative stress plays an important role during inflammatory diseases and recent
      therapies have focused on antioxidant administration to diminish oxidative stress
      and to arrest inflammatory processes. In this study, we investigated the impact
      of the GSH modulating effects of curcumin, a naturally derived polyphenol, on
      inflammatory processes in myelomonocytic U937 cells. One hour after
      administration of 10 micromol/l curcumin reactive oxygen species (ROS) production
      was significantly increased in undifferentiated U937 cells (+43%). Twenty-four
      hour after addition of curcumin, a significantly decreased ROS concentration was
      found (-32%), whereas GSH (+110%) and GSSG (+88%) content increased. A higher
      concentration of curcumin (25 micromol/l) caused an even stronger increase of GSH
      (+145%) and GSSG (+101%), but significantly decreased percentage of living cells
      to 84%. The increased GSH content of differentiated U937 cells after pre
      incubation with curcumin was associated with lowered ROS production, nuclear
      factor kappa B (NFkappaB) activation (-34%) and tumor necrosis factor alpha (TNF
      alpha) secretion (-51%) after LPS exposure. Curcumin inhibited TNF-alpha
      formation was also seen after GSH depletion by buthionine sulfoximine (BSO). This
      study shows that the antioxidative effects of curcumin are preceded by an
      oxidative stimulus, which is time and dose-dependent. Excessive concentrations of
      curcumin may even harm cells, as cell viability was decreased, in spite of
      elevated GSH contents. There was no clear relationship between intracellular GSH
      concentrations and the anti-inflammatory effects of curcumin.

PMID- 16002052
TI  - GnRH-immunoreactive centrifugal visual fibers in the Nile crocodile (Crocodylus
      niloticus).
AB  - Thin varicose centrifugal visual fibers, between 30-45 in number and displaying
      cGnRH-I immunoreactivity, were identified in Crocodylus niloticus. Approximately
      80% of these fibers were also FMRF-amide-like immunoreactive. The cGnRH-I fibers
      extended from the preoptic region to the retina where they appeared to terminate
      in the external portion of the inner plexiform layer. The location of their
      neurons of origin could not be determined precisely following the intraocular
      injection of the retrograde axonal tracer RITC. Nevertheless, the presence of
      cGnRH-I-immunoreactive neurons exclusively within the complex comprising the
      terminal nerve and the septo-preoptic region, and of several retinopetal fibers
      labelled retrogradely with the axonal tracer at the septo-preoptic junction,
      indicates that the cGnRH-immunoreactive centrifugal visual system originates from
      within this complex.

PMID- 16002053
TI  - Brief intermittent access to sucrose differentially modulates prepulse inhibition
      and acoustic startle response in obese CCK-1 receptor deficient rats.
AB  - Otsuka Long-Evans Tokushima Fatty (OLETF) rats lack the CCK-1 receptor and are
      hyperphagic and obese. CCK-1 receptors play a role in prepulse inhibition (PPI)
      by modulating mesolimbic dopamine transmission, a modulator of sensorimotor
      gating. Therefore, the present study assessed the effects of brief, daily sucrose
      access on PPI and acoustic startle response (ASR) in OLETF rat and age-matched
      non-mutant Long-Evans Tokushima Otsuka (LETO) rats. The results revealed that
      OLETF rats with sucrose access showed an increased ASR [F(1,16) = 6.84; P <
      0.01)], relative to sucrose receiving LETO rats. No significant sucrose effect (P
      = 0.283) on PPI was noted in OLETF rats, whereas sucrose receiving LETO rats had
      a significantly lower (P < 0.05) PPI percentage than non-sucrose controls. In
      contrast, sucrose-receiving OLETF rats expressed significantly higher PPI
      percentage than LETO rats with identical sucrose presentation (P < 0.01). Taken
      together, these results suggest that sucrose access alters PPI and ASR in
      general, and the CCK-1 receptors play a modulatory role in facilitating or
      inhibiting these responses, respectively. A similar effect may be contributory to
      the hyperphagic behavioral phenotype of obese animal models with altered central
      dopamine regulation.

PMID- 16002054
TI  - Age-related changes in cholinergic neurons in the laterodorsal and the pedunculo
      pontine tegmental nuclei of cats: a combined light and electron microscopic
      study.
AB  - In aged cats, light microscopic studies revealed significant decrease in the soma
      size of choline acetyltransferase (ChAT)-positive neurons in the laterodorsal and
      pedunculo-pontine tegmental nuclei (LDT and PPT), compared with adult control
      animals. In addition, a significant reduction of the total dendritic length and
      total dendritic segment number of ChAT-positive neurons was detected in both the
      LDT and PPT of aged cats. However, in contrast to the changes of soma and
      dendrites, no significant changes in the number of ChAT-positive neurons in aged
      were found comparing to that in the control cats in both the LDT and PPT; nor
      were there differences in the staining intensity of the somata of neurons in the
      adult and aged cats. Electron microscopic analysis highlighted degenerative
      changes in cholinergic neurons in the LDT and PPT of aged cats which included
      somata with intracytoplasmic vacuoles, darkened mitochondria, depletion of
      dendritic microtubules and severe demyelination of axons. These data indicate
      that profound atrophic changes occur in cholinergic systems of the LDT and PPT as
      a consequence of the aging process. These alterations likely reflect the cellular
      bases for the age-related changes in REM sleep that occur in old animals.

PMID- 16002055
TI  - Chiral recognition of dextran sulfate with D- and L-cystine studied by
      multiwavelength surface plasmon resonance.
AB  - A multiwavelength surface plasmon resonance (mwSPR) approach has been developed
      to study the chiral discrimination between D- and L-cystine (Cys). A monolayer of
      the two enantiomers was separately assembled on a pair of gold films of about 50
      nm in thickness and their resonance wavelength shifts, Deltalambda, were measured
      under a continuous flow of an identical chiral probe solution. Dextran sulfate
      (DS) was found to be an excellent chiral probe because it has rich chiral centers
      and is large enough to produce sensitive mwSPR response. The chiral
      discrimination was investigated either by Deltalambda(max), the maximum resonance
      wavelength shift in recognition equilibrium, or by recognition kinetics
      (Deltalambda vs time). The equilibrium data showed that D-Cys yielded always the
      smaller Deltalambda(max) as compared to L-Cys at pH 5.0 or above. This
      differentiation was enlarged by raising the probe content and became naught at pH
      <4.5. The kinetic results showed that, as pH increased from 5.0 to 7.5, the non
      equilibrium Deltalambda for D-Cys rose above the level for L-Cys at the first 30s
      of recognition but came back gradually to its equilibrium position after about
      150 s, with crossing at 50--150 s depending on DS concentration. This phenomenon
      was thought to be the result of molecular orientation adjustment after DS binding
      to D-Cys. Both kinetic and thermodynamic mechanisms were thus considered to be
      deeply involved in the investigated chiral recognition system.

PMID- 16002056
TI  - Expression and regulation of the atrial natriuretic factor encoding gene Nppa
      during development and disease.
AB  - The endocrine function of the heart was shown by the identification of a potent
      inhibitor of renal tubular NaCl reabsorbtion, atrial natriuretic peptide/factor
      (ANP), in atrial extracts. Since then, Nppa, the gene encoding ANP, has become an
      important tool for molecular and developmental biologists. Expression of Nppa is
      an early and specific marker for the differentiating working myocardium of the
      atria and ventricles of the developing heart. Around the time of birth,
      ventricular Nppa expression is down-regulated, to be reactivated in response to a
      variety of cardiovascular disorders. Many aspects of the regulatory pathways that
      control Nppa gene expression during cardiac development or disease have been
      revealed. However, several fundamental issues remain to be resolved.
      Particularly, the regulatory mechanisms underlying the ventricular Nppa
      expression in the embryonic heart and the reactivation in the failing ventricle
      remain unclear. Here we review current knowledge on the transcriptional
      regulation of the Nppa gene.

PMID- 16002057
TI  - Different effects of long- and short-acting loop diuretics on survival rate in
      Dahl high-salt heart failure model rats.
AB  - OBJECTIVES: We compared therapeutic effects of furosemide, a short-acting loop
      diuretic, and azosemide, a long-acting one, in hypertensive heart failure rats to
      test the hypothesis that long-acting diuretics are superior to short-acting types
      in heart failure. METHODS: Dahl salt-sensitive rats fed an 8% NaCl diet from age
      8 weeks were divided at age 21 weeks (compensated hypertrophic stage) into three
      groups: rats treated with furosemide (40 mg/kg/day), those treated with azosemide
      (80 mg/kg/day) and untreated rats. Rats fed a 0.3% NaCl diet served as controls.
      RESULTS: Both medications prevented left ventricular systolic dysfunction and
      enlargement at age 31 weeks, and attenuated macrophage infiltration, reactive
      oxygen species generation, and gelatinolytic activity to the same degree.
      Azosemide suppressed left ventricular fibrosis to the control level, but
      furosemide did not. Azosemide ameliorated myocardial catecholamine depletion and
      improved survival rate. Furosemide increased plasma norepinephrine levels and did
      not exert such beneficial effects. CONCLUSIONS: Azosemide provided better
      prognosis in heart failure rats compared with furosemide, partly through
      attenuation of the reflex increase in cardiac sympathetic neuronal activity
      caused by the development of heart failure. The current findings suggest a need
      for clinical trials examining whether long- and short-acting diuretics provide a
      different prognosis in patients with heart failure.

PMID- 16002058
TI  - Differential effects of oleuropein, a biophenol from Olea europaea, on anionic
      and zwiterionic phospholipid model membranes.
AB  - Oleuropein (Ole) is the major phenolic constituent of the olive leaf (Olea
      europaea) and it is also present in olive oil and fruit. In the last years
      several compounds from olive tree, oleuropein among them, have shown a variety of
      biological activities such as antimicrobial or antioxidant. A phospholipid model
      membrane system was used to study whether the Ole biological effects could be
      membrane related. Ole showed a significant partition level in phospholipid
      membranes, i.e. 80%, at lipid-saturating conditions. Moreover, fluorescence
      quenching experiments indicated a shallow location for Ole in membranes. Ole
      promoted weak effects on zwiterionic phospholipids such as phosphatidylcholine or
      phosphatidylethanolamine. In contrast, differential scanning microcalorimetry,
      light scattering and fluorescence anisotropy pH titration studies revealed strong
      effects on anionic phospholipids such as phosphatidylglycerol at physiological pH
      and salt conditions. These effects consisted on perturbations at the phospholipid
      membrane surface, which might involve specific molecular interactions between Ole
      and the negatively charged phosphate group and therefore modify the
      phospholipid/water interface properties. It is proposed that Ole induces lipid
      structures similar to the gel-fluid intermediate phase (IP) described for PG
      membranes, in a similar way than low ionic strength does. These effects on
      phosphatidylglycerol may account for the antimicrobial activity of Ole.

PMID- 16002059
TI  - Neat DODAB vesicles: Effect of sonication time on the phase transition
      thermodynamic parameters and its relation with incomplete chain freezing.
AB  - Vesicle solutions formed by the cationic lipid dioctadecyldimethylammonium
      bromide have been extensively used in the past 20 years as model membrane
      systems. Often, discrepancies are found in the literature for the thermodynamic
      parameters of the gel-to-liquid crystal (gel-lc) phase transition of these
      vesicles. In this work we present a systematic DSC investigation on the influence
      of the sonication method on the main temperature and enthalpy of the transition
      for DODAB vesicles, prepared both in normal and deuterated water. It is shown
      that as the sonication time increases, the T(m) and enthalpy values decrease
      until a plateau value is reached. This effect is associated with incomplete chain
      crystallization in the highly curved vesicles (produced by sonication) when they
      are cooled below the transition temperature. The effect of aging on the sonicated
      solutions has also been monitored by DSC.

PMID- 16002060
TI  - Molecular etiopathogenesis of limb girdle muscular and congenital muscular
      dystrophies: boundaries and contiguities.
AB  - The muscular dystrophies are a heterogeneous group of inherited disorders
      characterized by progressive muscle wasting and weakness. These disorders present
      a large clinical variability regarding age of onset, patterns of skeletal muscle
      involvement, heart damage, rate of progression and mode of inheritance.
      Difficulties in classification are often caused by the relatively common sporadic
      occurrence of autosomal recessive forms as well as by intrafamilial clinical
      variability. Furthermore recent discoveries, particularly regarding the proteins
      linking the sarcolemma to components of the extracellular matrix, have restricted
      the gap existing between limb girdle (LGMD) and congenital muscular dystrophies
      (CMD). Therefore a renewed definition of boundaries between these two groups is
      required. Molecular genetic studies have demonstrated different causative
      mutations in the genes encoding a disparate collection of proteins involved in
      all aspects of muscle cell biology. These novel skeletal muscle genes encode
      highly diverse proteins with different localization within or at the surface of
      the skeletal muscle fibre, such as the sarcolemmal muscle membrane (dystrophin,
      sarcoglycans, dysferlin, caveolin-3), the extracellular matrix (alpha2 laminin,
      collagen VI), the sarcomere (telethonin, myotilin, titin, nebulin and ZASP), the
      muscle cytosol (calpain-3, TRIM32), the nucleus (emerin, lamin A/C) and the
      glycosilation pathway enzymes (fukutin and fukutin related proteins). The
      accumulating knowledge about the role of these different proteins in muscle
      pathology has led to a profound change in the original phenotype-based
      classification and shed new light on the molecular pathogenesis of these
      disorders.

PMID- 16002061
TI  - Single nucleotide polymorphisms for DNA repair genes in breast cancer patients.
AB  - BACKGROUND: The incidence rate for breast cancer (BC) has been increasing in many
      countries and BC still remains the most common form of cancer in female and
      continues to be a major health problem worldwide. We explored the association of
      single nucleotide polymorphisms (SNPs) in DNA repair genes with breast cancer.
      METHODS: SSCP and RFLP were used to analyze genotypes of DNA repair genes for
      NBS1, XPC, XPD and XRCC3. RESULTS: T/C in XRCC3 exon 7 had a somewhat deviation
      from HWE in BC group (P=0.08). The genotype frequency for heterozygote A/C in XPC
      exon 15 and T/C in XRCC3 exon 7, homozygote A/A in XPD exon 10 were significantly
      different between BC group and control group in Chinese population (P<0.05,
      OR=1.47, 95% CI, 1.00-2.16 for A/C in XPC exon 15; P<0.05, OR=1.79, 95% CI, 0.98
      3.26 for T/C in XRCC3 exon 7; P<0.05, OR=0.51, 95% CI, 0.27-0.94 for G/A in XPD
      exon 10). For the SNPs in NBS1 exon 5 (Glu185Gln, G/C) and XPD exon 23
      (Lys751Gln, A/C), no remarkable difference for genotype distributions and allele
      frequencies was observed between BC group and control group in the study.
      CONCLUSIONS: The genotypes of A/C in XPC exon 15, T/C in XRCC3 exon 7 and A/A in
      XPD exon 10 studied were significantly different between BC group and control
      group in Chinese population.

PMID- 16002062
TI  - Serum angiotensin converting enzyme activity association with the I/D
      polymorphism in an ethnically admixtured population.

PMID- 16002063
TI  - N-terminal-pro-B-type natriuretic peptide (NT-proBNP): reference range for
      Chinese apparently healthy people and clinical performance in Chinese elderly
      patients with heart failure.
AB  - BACKGROUND: N-terminal-pro-B-type natriuretic peptide (NT-proBNP) has been found
      to be a useful marker for the diagnosis of heart failure (HF) and left
      ventricular systolic dysfunction. We established a reference range for Chinese
      apparently healthy people based on age and gender and evaluated the clinical
      performance of NT-proBNP in the diagnosis of asymptomatic and symptomatic HF.
      METHODS: A group of 442 apparently healthy subjects were enrolled for reference
      range study. For the clinical performance study, serum NT-proBNP and clinical
      data were analyzed in 111 elderly patients with HF and 60 normal elderly
      controls. Serum NT-proBNP was measured by the Roche Elecsys 2010 immunoassay
      analyzer. RESULTS: NT-proBNP reference range in Chinese people based on age and
      gender was <83.72 ng/l for men and <131.6 ng/l for women aged <or=60 years, and
      <158.17 ng/l for men and <205.54 ng/l for women aged >60 years, which were lower
      than those for western countries. NT-proBNP had a close correlation with New York
      Heart Association (NYHA) classification (r=0.818) and LVEF (r=-0.636). The ROC
      curve analysis revealed an AUC of 0.921 for the diagnosis of HF, 0.840 for
      asymptomatic HF (NYHA I) and 0.951 for symptomatic HF (NYHA II-IV). The optimal
      cutoff values for detecting HF, asymptomatic HF and symptomatic HF were 102.2,
      102.2, and 204.8 ng/l, respectively. NT-proBNP had high positive predictive value
      (PPV) for the diagnosis of HF (96.8%), asymptomatic HF (90.3%) and symptomatic HF
      (90.9%), but low negative predictive value (NPV) for diagnosing HF and
      asymptomatic HF (74.0% and 78.1%, respectively) except symptomatic HF (93.3%).
      CONCLUSIONS: Chinese people have lower reference range of serum NT-proBNP. NT
      proBNP assay has a good clinical performance for the diagnosis of symptomatic HF
      but is not suitable as a screening test for HF.

PMID- 16002064
TI  - Effects of a 5-HT7 receptor antagonist DR4004 on the exploratory behavior in a
      novel environment and on brain monoamine dynamics in mice.
AB  - The present study examined whether serotonin (5-hydroxytryptamine; 5-HT)7
      receptors play a role in the modulation of emotionality in mice using the
      selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6
      tetrahydropyridyl)butyl]-2a,3,4,5-tetrahydrobenzo (c,d)indol-2-(1H)-one (DR4004).
      The emotionality of mice was evaluated in terms of exploratory activity in the
      hole-board test. The mice treated with DR4004 (2.5-10 mg/kg, i.p.) displayed a
      dose-dependent decrease in locomotor activity by moving less distance in the hole
      board, and statistically significant decreases were observed at 5 and 10 mg/kg.
      On the other hand, DR4004 (10 mg/kg, i.p.) did not affect spontaneous motor
      activity. In a neurochemical study, decreases in amygdaloid dopamine and 5-HT
      turnover were observed in mice in which locomotor activity in the hole-board test
      was attenuated following the administration of DR4004 (10 mg/kg, i.p.). Also, a
      simple linear regression analysis revealed that locomotor activity on the hole
      board was significantly correlated with dopamine and 5-HT turnover in amygdala.
      Furthermore, co-injection of the selective dopamine reuptake inhibitor 1-(2
      [bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR12909; 1.25-5
      mg/kg, i.p.) or the selective 5-HT reuptake inhibitor fluvoxamine (20 mg/kg,
      i.p.) significantly reversed the DR4004 (10 mg/kg, i.p.)-induced decrease in
      locomotor activity in the hole-board test. These findings constitute the
      behavioral evidence that 5-HT7 receptors may play a role in the modulation of
      emotionality. Furthermore, it is also suggested that amygdaloid dopamine and 5-HT
      neuronal systems may be involved in this modulation.

PMID- 16002065
TI  - A conserved, extended chromatin opening within alpha-globin locus during
      development.
AB  - Histone modifications play an important role in eukaryotic gene regulation.
      However, the dynamic alteration of histone modification during development is
      poorly understood. In addition, the relationship between histone modification and
      globin gene switching remains unclear. Here, we assessed the dynamic pattern of
      histone modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3
      K79 methylation) along the murine alpha-globin locus, as well as along the human
      alpha-globin locus in transgenic mice, during globin gene switching in vivo.
      During the switching, histone modification at embryonic zeta-gene and fetal/adult
      alpha-genes displayed different developmental patterns. The level of histone
      modification at zeta-gene was developmentally regulated, in accordance with the
      level of zeta-gene expression, whereas the alpha-genes kept high level of histone
      modification at both developmental stages, regardless of their expression levels.
      Histone deacetylase inhibition selectively increased acetylation at the inactive
      zeta-gene in fetal livers, although it did not reactivate the gene expression.
      More importantly, an obvious increasing of histone modification level at major
      regulatory elements and fetal/adult alpha-genes was observed during the
      switching, suggesting that a conserved, extended chromatin opening within the
      locus occurs during globin gene switching.

PMID- 16002066
TI  - Regulation of potassium transport in human lens epithelial cells.
AB  - The major K influx pathways and their response to thiol modification by N
      ethylmaleimide (NEM) and protein kinase and phosphatase inhibitors were
      characterized in human lens epithelial B3 (HLE-B3) cells with Rb as K congener.
      Ouabain (0.1 mM) and bumetanide (5 microM) discriminated between the Na/K pump (
      approximately 35% of total Rb influx) and Na-K-2Cl cotransport (NKCC) (
      approximately 50%). Cl-replacement with nitrate or sulfamate revealed <10%
      residual [ouabain+bumetanide]-insensitive K-Cl cotransport (KCC). At 0.3-0.5 mM,
      NEM stimulated the Na/K pump by 2-fold independent of external Na, KCC between 2
      and 4-fold, and abolished approximately 90% of NKCC. Calyculin-A, a
      serine/threonine protein phosphatase-1 inhibitor, did not affect NKCC but
      inhibited KCC, whereas 10 microM staurosporine, a serine/threonine kinase
      inhibitor, abolished NKCC, and stimulated KCC only when followed by NEM
      treatment. The tyrosine-kinase inhibitor genistein, at concentrations >100
      microM, activated the Na/K pump and abolished NKCC but did not affect KCC. The
      data suggest at least partial inverse regulation of KCC and NKCC in HLE-B3 cells
      by signaling cascades involving serine, threonine and tyrosine
      phosphorylation/dephosphorylation equilibria.

PMID- 16002067
TI  - Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element
      binding protein and neuropeptide Y decline as early as middle age in the dentate
      gyrus and CA1 and CA3 subfields of the hippocampus.
AB  - The hippocampus is very susceptible to aging. Severely diminished dentate
      neurogenesis at middle age is one of the most conspicuous early changes in the
      aging hippocampus, which is likely linked to an early decline in the
      concentration of neurotrophic factors and signaling proteins that influence
      neurogenesis. We analyzed three proteins that are well-known to promote dentate
      neurogenesis and learning and memory function in the dentate gyrus and the
      hippocampal CA1 and CA3 subfields of young, middle-aged and aged F344 rats. These
      include the brain-derived neurotrophic factor (BDNF), the transcription factor
      phosphorylated cyclic AMP response element binding protein (p-CREB) and the
      neuropeptide neuropeptide Y (NPY). The BDNF was analyzed via ELISA and BDNF
      immunohistochemistry, the p-CREB through densitometric analysis of p-CREB
      immunopositive cells, and the NPY via stereological counting of NPY
      immunopositive interneurons. We provide new evidence that the BDNF concentration,
      the p-CREB immunoreactivity and the number of NPY immunopositive interneurons
      decline considerably by middle age in both dentate gyrus and CA1 and CA3
      subfields of the hippocampus. However, both BDNF concentration and NPY
      immunopositive interneuron numbers exhibit no significant decrease between middle
      age and old age. In contrast, the p-CREB immunoreactivity diminishes further
      during this period, which is also associated with reduced BDNF immunoreaction
      within the soma of dentate granule cells and hippocampal pyramidal neurons.
      Collectively, these results suggest that severely dampened dentate neurogenesis
      observed at middle age is linked at least partially to reduced concentrations of
      BDNF, p-CREB and NPY, as each of these proteins is a positive regulator of
      dentate neurogenesis. Dramatically diminished CREB phosphorylation (and
      persistently reduced levels of BDNF and NPY) at old age may underlie the learning
      and memory impairments observed during senescence.

PMID- 16002068
TI  - Effects of androgens and estrogens on crowings and distress callings in male
      Japanese quail, Coturnix japonica.
AB  - In male Japanese quail, crowing behavior is considered to be strictly androgen
      dependent. It was previously shown that in chicks, treatment with either
      testosterone or 5alpha-dihydrotestosterone (5alpha-DHT; a non-aromatizable
      androgen) induced crowing with motivation for distress calling in acutely
      isolated conditions. Many studies, however, have shown that the potencies of
      testosterone and 5alpha-DHT in activating crowing in castrated males are
      different. To clarify the effects of androgenic and estrogenic actions on the
      production of crows and distress calls, we injected quail daily from 11 to 42
      days after hatching (Day 11 to 42) with testosterone propionate (TP), 5alpha-DHT,
      estradiol benzoate (EB) or vehicle and examined their calling behaviors both in a
      recording chamber (acutely isolated conditions) and in their home-cages (well
      acclimated conditions). Both TP- and 5alpha-DHT-treated birds began to crow by
      Day 13 when isolated in the recording chamber. The TP-treated birds, however,
      crowed less frequently than 5alpha-DHT-treated ones. This, combined with the
      observations that distress calling was strongly inhibited in EB-treated birds,
      suggests that estrogen converted from testosterone may inhibit the motivation for
      distress calling. On the other hand, after chronic treatment of TP, but not of
      5alpha-DHT, birds began to crow intensely in their home-cages earlier than
      vehicle treated controls, suggesting that estrogen is needed to initiate crowing
      behavior in sexually active males. Taken together, it is suggested that
      estrogenic actions affect the motivation underlying vocal behaviors, while the
      androgenic action is indispensable in generating crowing.

PMID- 16002069
TI  - Post-operative mortality related to waiting time for hip fracture surgery.

PMID- 16002070
TI  - Repair of postintubation tracheoesophageal fistula in polytrauma patients.
AB  - OBJECTIVE: We present our modest experience in treating tracheoesophageal fistula
      (TEF) in polytrauma patients where tracheal resection turns to be risky due to
      the size of the fistula and to the general condition of the patient. MATERIALS
      AND METHODS: Four polytrauma patients, three male and one female were treated at
      our department due to postintubation TEF. Confirmation was obtained
      endoscopically and radiologically. Surgical treatment consisted of identification
      and dissection of the fistulous tract and closure of the tracheal defect by
      transposing strap muscles and suturing them to the defect. Finally, the
      oesophageal defect was closed and a flap of sternocleidomastoid muscle was
      interposed between oesophagus and trachea. RESULTS: There was no intraoperative
      mortality. Three of our patients had an excellent result. The one who
      unfortunately returned to mechanical ventilation due to respiratory insufficiency
      developed a recurrent fistula. CONCLUSIONS: (1) Repair of postintubation TEF
      should be delayed until the patient is fully stabilised and weaned from
      ventilation. (2) Indirect closure of the tracheal defect with strap muscle
      transposition and sternocleidomastoid muscle interposition between oesophagus and
      trachea can be lifesaving.

PMID- 16002073
TI  - Effect of praziquantel on the immature stages of Schistosoma haematobium.
AB  - Schistosoma mansoni is known to be refractory to praziquantel treatment in the
      pre-patent period of infection. Since Schistosoma haematobium has a much longer
      pre-patent period (10-12 weeks vs. 5-6 for the former species), we asked the
      question whether a correspondingly longer period of insusceptibility exists in
      urinary schistosomiasis. In hamsters treated at different times after infection,
      S. haematobium was partially refractory to praziquantel when treatment was given
      at week 5, but showed practically full sensitivity at 7-8 weeks and later times.
      Schistosoma haematobium worms obtained at different times after infection and
      exposed in vitro to praziquantel were refractory to low drug concentrations
      between 4 and 6 weeks, but were clearly affected at higher concentrations and at
      later time points. We conclude that S. haematobium does not have a praziquantel
      insensitive window longer than in S. manson, in spite of its much longer
      maturation period. In addition, refractoriness of immature stages can be overcome
      at higher drug concentrations.

PMID- 16002074
TI  - The association of common SNPs and haplotypes in the CETP and MDR1 genes with
      lipids response to fluvastatin in familial hypercholesterolemia.
AB  - OBJECTIVE: To examine whether genetic polymorphisms in the cholesteryl-ester
      transfer protein (CETP) and the P-glycoprotein drug transporter (MDR1), are
      associated with variable lipid response to fluvastatin. METHODS: Lipid levels
      were determined in a compliance-monitored clinical study at baseline and
      following 20 weeks of treatment with 40 mg dose of fluvastatin in 76 FH patients.
      CETP and MDR1 SNP genotyping was performed and linear regression was used to
      examine the associations between common SNPs and haplotypes and lipid response.
      RESULTS: Treatment with 40 mg of fluvastatin resulted in mean low density
      lipoprotein cholesterol (LDL-C) reduction of 21.5%; mean triglyceride (TG)
      reduction of 8.3%; and a mean high-density lipoprotein cholesterol (HDL-C)
      increase of 13.4%. Five tagging SNPs in both genes were used to reconstruct five
      and six haplotypes accounting for 71.4% and 90.2% of the observed haplotypes in
      the CETP and MDR1 genes, respectively. CETP-H13 and MDR1-h4 were associated with
      an increase in LDL-C response. CETP-H5 was significantly associated with
      decreased TG and HDL-C response, whereas MDR1-h10 was associated with decreased
      TG response. A multivariate regression model indicated an independent additive
      effect of CETP-H5 and MDR1-h10 on the level of TG response. CONCLUSIONS: CETP and
      MDR1 have independent effects on lipid changes following fluvastatin treatment.
      The results of this study may lead to an improved understanding of the genetic
      determinants of lipids response to treatment.

PMID- 16002075
TI  - C-reactive protein induces VCAM-1 gene expression through NF-kappaB activation in
      vascular endothelial cells.
AB  - Recent studies have shown that C-reactive protein (CRP) is not just a predictor
      of cardiovascular events but also acts directly as a proinflammatory stimulus in
      vascular cells. In this report, we studied the molecular mechanisms underlying
      vascular cellular adhesion molecule-1 (VCAM-1) induction by CRP. CRP-induced VCAM
      1 mRNA expression and this induction was inhibited by protein kinase C (PKC)
      inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and tyrosine
      kinase inhibitors. In addition, parthenolide, a nuclear factor kappaB (NF-kappaB)
      inhibitor, abolished VCAM-1 induction. Moreover, CRP increased VCAM-1 promoter
      activity, indicating that CRP induces VCAM-1 mRNA expression at the
      transcriptional level. Mutation of NF-kappaB-binding sites resulted in a loss of
      induction. Finally, an electrophoretic mobility shift assay confirmed binding of
      the p65 subunit of NF-kappaB to kappaB-binding sites. Taken together, our
      findings suggest that VCAM-1 induction by CRP is mediated by PKC, p38MAPK,
      tyrosine kinase and the NF-kappaB-dependent signaling pathways in vascular
      endothelial cells.

PMID- 16002076
TI  - Leukocyte CD40L deficiency affects the CD25(+) CD4 T cell population but does not
      affect atherosclerosis.
AB  - Inhibition of CD40-CD40L interactions results in a reduction of innate regulatory
      T cells (Tregs) in CD40(-/-) mice and induces a stable plaque phenotype in
      atherosclerosis-prone mouse strains. Here we investigated the effects of
      leukocyte CD40L on the Treg population and on atherosclerosis. LDLR(-/-) mice
      were reconstituted with wild-type or CD40L(-/-) bone marrow (BM). These BM
      chimeras were analysed by flow cytometry for the presence of innate Tregs
      (CD45RB(low) CD25(+) CD4) in lymphoid organs and peripheral blood. As in CD40(-/
      ) mice, the CD45RB(high):CD45RB(low) CD4 T cell ratio significantly increased and
      the CD25(+) CD4(+) subpopulation significantly decreased in LDLR(-/-) mice
      receiving CD40L(-/-) BM compared to LDLR(-/-) mice receiving wild-type BM.
      However, atherosclerotic plaque progression and plaque phenotype did not change
      in LDLR(-/-) mice reconstituted with CD40L(-/-) BM. In conclusion, the present
      study shows that CD40-CD40L interactions on leukocytes are essential for the size
      of the CD45RB(low) CD25(+) CD4 Treg subpopulation. Nevertheless, CD40L deficiency
      on hemopoietic cells did not affect atherosclerosis, implying that CD40L
      expressing leukocytes alone are not responsible for the stable plaque phenotype
      observed after total CD40L blockade.

PMID- 16002077
TI  - A common variant in the glutathione S transferase gene is associated with
      elevated markers of inflammation and lipid peroxidation in subjects with diabetes
      mellitus.
AB  - INTRODUCTION: Glutathione S transferases (GST) are enzymes responsible for the
      metabolism of numerous xenobiotics and play a major cellular antioxidant role.
      Our aim was firstly, to examine the association between the GST M1/GST mu-1
      (GSTM1) and GST T1/GST theta-1 (GSTT1) gene variants with markers of oxidative
      stress and inflammation in diabetic patients, and secondly to examine the
      association and potential interaction between these variants and cigarette
      smoking. METHODS: Seven hundred and seventy-three Caucasian subjects with
      diabetes and 2592 Caucasian non-diabetic subjects were successfully genotyped.
      Plasma total antioxidant status, C-reactive protein (CRP), oxidized-LDL (Ox-LDL)
      and LDL-mean/peak particle diameter were recorded in the diabetes sample.
      RESULTS: No association was seen between genotype and cardiovascular disease
      (CVD) risk. In the diabetic subjects, GSTT1-1 compared to GSTT1-0 subjects had
      significantly higher CRP (p=0.001), Ox-LDL (p=0.004) and smaller LDL particles
      (p=0.01). In subjects without CVD, there was a significant interaction between
      the GSTT1-1 variant and smoking in determining Ox-LDL (p=0.04). Furthermore, CVD
      risk was higher in smokers compared to non-smokers with GSTT1-1. No significant
      associations were observed by GSTM1. Within the non-diabetic sample, no
      association was observed between genotype and prospective coronary heart disease
      (CHD) risk. Of note, the frequency of the GSTT1-1 variant was significantly lower
      in the diabetes subjects compared to the non-diabetic sample (p=0.01).
      CONCLUSIONS: This study demonstrates an association between the GSTT1-1 variant
      and markers of inflammation and lipid peroxidation. Furthermore this variant
      interacts with smoking to increase lipid peroxidation.

PMID- 16002078
TI  - Effect of rosuvastatin on hepatic production of apolipoprotein B-containing
      lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia.
AB  - A novel animal model of insulin resistance, the fructose-fed Syrian golden
      hamster, was employed to investigate the efficacy and mechanisms of action of
      rosuvastatin, a HMG-CoA reductase inhibitor, in ameliorating metabolic
      dyslipidemia in insulin-resistant states. Fructose feeding for a 2-week period
      induced insulin resistance and a significant increase in hepatic secretion of
      VLDL. This was followed by a fructose-enriched diet with or without 10 mg/kg
      rosuvastatin for 14 days. Fructose feeding in the first 2 weeks caused a
      significant increase in plasma total cholesterol and triglyceride in both groups
      (n=6, p<0.001). However, there was a significant decline (30%, n=8, p<0.05) in
      plasma triglyceride levels following rosuvastatin feeding (10 mg/kg). A
      significant decrease (n=6, p<0.05) was also observed in VLDL-apoB production in
      hepatocytes isolated from drug-treated hamsters, together with an increased apoB
      degradation (n=6, p<0.05). Similar results were obtained in parallel cell culture
      experiments in which primary hepatocytes were first isolated from chow-fed
      hamsters, and then treated in vitro with 15 microM rosuvastatin for 18 h.
      Rosuvastatin at 5 microM caused a substantial reduction in synthesis of
      unesterified cholesterol and cholesterol ester (98 and 25%, n=9, p<0.01 or
      p<0.05) and secretion of newly synthesized unesterified cholesterol, cholesterol
      ester, and triglyceride (95, 42, and 60% reduction, respectively, n=9, p<0.01 or
      p<0.05). This concentration of rosuvastatin also caused a significant reduction
      (75% decrease, n=4, p<0.01) in the extracellular secretion of VLDL-apoB100,
      accompanied by a significant increase in the intracellular degradation of
      apoB100. There was a 12% reduction (not significant, p>0.05) in hepatic MTP and
      no changes in ER-60 (a chaperone involved in apoB degradation) protein levels.
      Taken together, these data suggest that the assembly and secretion of VLDL
      particles in hamster hepatocytes can be acutely inhibited by rosuvastatin in a
      process involving enhanced apoB degradation. This appears to lead to a
      significant amelioration of hepatic VLDL-apoB overproduction observed in the
      fructose-fed, insulin-resistant hamster model.

PMID- 16002079
TI  - Relevance of mandibular helical axis analysis in functional and dysfunctional
      TMJs.
AB  - The helical axis (HA), or motion screw, yields a comprehensive description of
      joint motion. The perspective representation of this axis clearly visualizes the
      regularity of mandibular functional movements (Yatabe et al. 1997. Journal of
      Dentist Research 76, 714-719 and Gallo et al. 2000. Journal of Dental Research
      79, 1566-1572). In this study, the sensitivity of the HA representation was
      investigated relative to (a) irregularities in pathologic motion of clicking
      temporomandibular joints (TMJs) for jaw opening/closing and (b) differences in
      food bolus size and consistency for unilateral mastication in subjects with
      normal TMJs. Mandibular motion relative to the head was acquired using a jaw
      tracker with six degrees-of-freedom with a sampling frequency of 70 Hz. The HA
      was calculated according to an eigenvalue method (Spoor and Veldpaus 1980.
      Journal of Biomechanics 13, 391-393) and parameters were defined describing its
      position and orientation relative to the anatomy. We analyzed 39 subjects with
      unilateral or bilateral reciprocal TMJ clicking during jaw opening/closing and
      seven asymptomatic subjects during unilateral mastication of five different types
      of soft and hard food in two different bolus sizes. The results showed a greater
      variability of the HA parameters in the group of clicking joints than in the
      asymptomatic group: in particular, the area in which the HA moved was wider in
      clicking joints than in normal ones and the HA in clicking TMJs had a much
      greater fluctuation than in normal ones. During unilateral mastication, for more
      consistent food or a bigger bolus the HA showed a significantly greater excursion
      of the orientation parameters. Furthermore a significantly greater excursion of
      the dorsoventral and of the craniocaudal component of the distance vector from
      the HA to the condyle were found. The helical axis analysis of mandibular
      movements was sensitive to kinematic irregularities of the mandible due to an
      internal joint derangement as well as to differences in food bolus size and
      consistency.

PMID- 16002080
TI  - Determination of subject-specific model parameters for visco-elastic elements.
AB  - The determination of subject-specific model parameter values is necessary in
      order for a computer simulation model of human motion to be evaluated
      quantitatively. This study used an optimisation procedure along with a
      kinematically driven simulation model of the contact phase in running jumps to
      determine the elastic parameters of segmental wobbling masses and the foot-ground
      interface. Kinetic and kinematic data were obtained on running jumps for height
      and distance performed by an elite male high jumper. Stiffness and damping
      coefficients of the visco-elastic elements in the model were varied until the
      difference between simulation and performance was minimised. Percentage
      differences of 6% and 9% between the simulated and recorded performances were
      obtained in the jumps for height and distance, respectively. When the parameters
      obtained from the jump for height were used in a simulation of the jump for
      distance (and vice versa), there was poor agreement with the recorded jump. On
      the other hand, a common set of visco-elastic parameters were obtained using the
      data from both recorded jumps resulting in a mean difference of only 8% (made up
      of 7% and 10%) between simulation and performance that was almost as good as the
      individual matches. Simulations were not overly sensitive to perturbations of the
      common set of visco-elastic parameters. It is concluded that subject-specific
      elastic parameters should be calculated from more than a single jump in order to
      provide a robust set of values that can be used in different simulations.

PMID- 16002081
TI  - Characteristics of activated carbon prepared from pistachio-nut shell by zinc
      chloride activation under nitrogen and vacuum conditions.
AB  - Activated carbons with well-developed pore structures were prepared from
      pistachio-nut shells by chemical activation using zinc chloride under both
      nitrogen atmosphere and vacuum conditions. The effects of preparation parameters
      on the carbon pore structure were studied in order to optimize these parameters.
      It was found that under vacuum conditions, the characteristics of the activated
      carbons produced are better than those under nitrogen atmosphere. The
      impregnation ratio, the activation temperature, and the activation hold time are
      the important parameters that influence the characteristics of the activated
      carbons. The optimum experimental conditions for preparing predominantly
      microporous activated carbons with high pore surface area and micropore volume
      are an impregnation ratio of 0.75, an activation temperature of 400 degrees C,
      and a hold time of 1 h. Under these conditions, the BET surface areas of the
      carbons activated under nitrogen atmosphere and vacuum conditions were 1635.37
      and 1647.16 m2/g, respectively. However, at a ZnCl2 impregnation ratio of 1.5, a
      furnace temperature of 500 degrees C, and a hold time of 2 h, the predominantly
      mesoporous activated carbon prepared under vacuum condition had a BET surface
      area of 2527 m2/g. Fourier transform infrared spectra were used to detect changes
      in the surface functional groups of the samples during the different preparation
      stages.

PMID- 16002082
TI  - Simplified method to automatically count bacterial colony forming unit.
AB  - Bacterial colony counting is a significant technical hurdle for vaccine studies
      as well as various microbiological studies. We now show that an automated colony
      counter can process images obtained with a digital camera or document scanner and
      that any laboratory can efficiently have bacterial colonies enumerated by sending
      the images to a laboratory with a colony counter via internet.

PMID- 16002083
TI  - The calyx fluid of Microplitis rufiventris parasitoid and growth of its host
      Spodoptera littoralis larvae.
AB  - The morphology of the female reproductive system of pupal and adult stages of
      Microplitis rufiventris and the ultrastructure of the ovaries are described and
      illustrated. Two morphologically distinct types of particles of nuclear origin,
      i.e., polydnavirus (PDV) and a virus-like filamentous particle (VLFP) were
      detected in the ovarian calyx fluid of the female wasp. It is likely that these
      particles are injected into the host during oviposition. PDV initiated
      replication in the calyx of mid-aged pupae and in pharate adults and were present
      throughout adult life. VLFP were only seen in the calyx fluid of newly emerged
      adults, and therefore observed after the PDV. Feulgen and methyl-green pyronin
      staining revealed the presence of DNA in both types of particles. The effects of
      injection of Spodoptera littoralis larvae with a combination of parasitoid
      viruses and venom of M. rufiventris females (CxFV) were investigated and the
      results were compared with two control groups, i.e., larvae injected with
      Pringle's saline (PS) and naturally parasitized larvae. CxFV-larvae showed
      significant declines (P<0.05) in food consumption, weight of ejected faeces and
      weight gain when compared with PS-larvae. However, naturally parasitized larvae
      (parasitoid egg+CxFV+ovarian protein) displayed a high significance score
      (P<0.01) in comparison with those of PS-larvae. The approximate digestibility
      (AD) values of S. littoralis larvae were positively affected as early as day 2
      post-treatment by either injection of CxFV or parasitization. However, a
      reduction in AD was observed in both PS- and CxFV-larvae on day 3-7 in comparison
      with naturally parasitized larvae. Other indices of food utilization were
      unchanged in CxFV-larvae when compared to saline treated or parasitized controls.

PMID- 16002084
TI  - Translocation of nicked but not gapped DNA by the packaging motor of
      bacteriophage phi29.
AB  - The biomolecular mechanism that the double-stranded DNA viruses employ to insert
      and package their genomic DNA into a preformed procapsid is still elusive. To
      better characterize this process, we investigated packaging of bacteriophage
      phi29 DNA with structural alterations. phi29 DNA was modified in vitro by nicking
      at random sites with DNase I, or at specific sites with nicking enzyme N.BbvC IA.
      Single-strand gaps were created by expanding site-specific nicks with T4 DNA
      polymerase. Packaging of modified phi29 DNA was studied in a completely defined
      in vitro system. Nicked DNA was packaged at full genome length and with the same
      efficiency as untreated DNA. Nicks were not repaired during packaging. Gapped DNA
      was packaged only as a fragment corresponding to the DNA between the genome
      terminus and gap. Thus the phi29 DNA packaging machinery tolerated nicks, but
      stopped at gaps. The packaging motor did not require a nick-free DNA backbone,
      but the presence of both DNA strands, for uninterrupted packaging.

PMID- 16002085
TI  - Atomic-resolution crystal structure of the proteolytic domain of Archaeoglobus
      fulgidus lon reveals the conformational variability in the active sites of lon
      proteases.
AB  - The atomic-resolution crystal structure of the proteolytic domain (P-domain,
      residues 415-621) of Archaeoglobus fulgidus B-type Lon protease (wtAfLonB) and
      the structures of several mutants have revealed significant differences in the
      conformation of the active-site residues when compared to other known Lon P
      domains, despite the conservation of the overall fold. The catalytic Ser509 is
      facing the solvent and is distant from Lys552, the other member of the catalytic
      dyad. Instead, the adjacent Asp508 forms an ion pair with the catalytic lysine
      residue. Glu506, an analog of the putative third catalytic residue from a related
      Methanococcus jannaschii LonB, also faces the solvent and does not interact with
      the catalytic dyad. We have established that full-length wtAfLonB is
      proteolytically active in an ATP-dependent manner. The loss of enzymatic activity
      of the S509A mutant confirms the functional significance of this residue, while
      retention of considerable level of activity by the D508A and E506A mutants rules
      out their critical involvement in catalysis. In contrast to the full-length
      enzymes, all individually purified P-domains (wild-type and mutants) were
      inactive, and the mutations had no influence on the active-site structure. These
      findings raise the possibility that, although isolated proteolytic domains of
      both AfLonB and E.coli LonA are able to assemble into expected functional
      hexamers, the presence of the other domains, as well as substrate binding, may be
      needed to stabilize the productive conformation of their active sites. Thus, the
      observed conformational variability may reflect the differences in the stability
      of active-site structures for the proteolytic counterparts of single-chain Lon
      versus independently folded proteolytic subunits of two-chain AAA+ proteases.

PMID- 16002086
TI  - Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation.
AB  - The C-terminal Src kinase (Csk) phosphorylates and down-regulates Src family
      tyrosine kinases. The Csk-binding protein (Cbp) localizes Csk close to its
      substrates at the plasma membrane, and increases the specific activity of the
      kinase. To investigate this long-range catalytic effect, the phosphorylation of
      Src and the conformation of Csk were investigated in the presence of a high
      affinity phosphopeptide derived from Cbp. This peptide binds tightly to the SH2
      domain and enhances Src recognition (lowers K(m)) by increasing the apparent
      phosphoryl transfer rate in the Csk active site, a phenomenon detected in rapid
      quench flow experiments. Previous studies demonstrated that the regulation of Csk
      activity is linked to conformational changes in the enzyme that can be probed
      with hydrogen-deuterium exchange methods. We show that the Cbp peptide impacts
      deuterium incorporation into its binding partner (the SH2 domain), and into the
      SH2-kinase linker and several sequences in the kinase domain, including the
      glycine-rich loop in the active site. These findings, along with computational
      data from normal mode analyses, suggest that the SH2 domain moves in a cantilever
      fashion with respect to the small lobe of the kinase domain, ordering the active
      site for catalysis. The binding of a small Cbp-derived peptide to the SH2 domain
      of Csk modifies these motions, enhancing Src recognition.

PMID- 16002087
TI  - The Bacillus subtilis DnaD and DnaB proteins exhibit different DNA remodelling
      activities.
AB  - Primosomal protein cascades load the replicative helicase onto DNA. In Bacillus
      subtilis a putative primosomal cascade involving the DnaD-DnaB-DnaI proteins has
      been suggested to participate in both the DnaA and PriA-dependent loading of the
      replicative helicase DnaC onto the DNA. Recently we discovered that DnaD has a
      global remodelling DNA activity suggesting a more widespread role in bacterial
      nucleoid architecture. Here, we show that DnaB forms a "square-like" tetramer
      with a hole in the centre and suggest a model for its interaction with DNA. It
      has a global DNA remodelling activity that is different from that of DnaD.
      Whereas DnaD opens up supercoiled DNA, DnaB acts as a lateral compaction protein.
      The two competing activities can act together on a supercoiled plasmid forming
      two topologically distinct poles; one compacted with DnaB and the other open with
      DnaD. We propose that the primary roles of DnaB and DnaD are in bacterial
      nucleoid architecture control and modulation, and their effects on the initiation
      of DNA replication are a secondary role resulting from architectural
      perturbations of chromosomal DNA.

PMID- 16002088
TI  - The length of the 5' leader of Escherichia coli tRNA precursors influences
      bacterial growth.
AB  - Based on a computational analysis of the 5' regions of tRNA-encoding genes, the
      average length of the 5' leaders in tRNA precursors in Escherichia coli appears
      to be 17-18 residues long. An in vivo assay based on tRNA nonsense suppression
      was developed and used to investigate the function of the 5' leader of the tRNA
      precursors on tRNA processing and bacterial growth. Our data indicate that the 5'
      leader influences bacterial growth but is surprisingly not absolutely necessary
      for growth. These findings are consistent with previous in vitro data where it
      was demonstrated that the 5' leader plays a role in the interaction with RNase P,
      the endoribonuclease responsible for removing the 5' leader in the cell. We
      discuss the plausible role of the 5' leader in processing and tRNA gene
      expression.

PMID- 16002089
TI  - Forced unraveling of nucleosomes assembled on heterogeneous DNA using core
      histones, NAP-1, and ACF.
AB  - Periodic arrays of nucleosomes were assembled on heterogeneous DNA using core
      histones, the histone chaperone NAP-1, and ATP-dependent chromatin assembly and
      remodeling factor (ACF). The mechanical properties of these complexes were
      interrogated by stretching them with optical tweezers. Abrupt events releasing
      approximately 55-95 base-pairs of DNA, attributable to the non-equilibrium
      unraveling of individual nucleosomes, were frequently observed. This finding is
      comparable with a previous observation of 72-80 bp unraveling events for
      nucleosomes assembled by salt dialysis on a repeating sea urchin 5 S RNA
      positioning element, but the unraveling force varied over a wider range (
      approximately 5-65 pN, with the majority of events at lower force). Because ACF
      assembles nucleosomes uniformly on heterogeneous DNA sequences, as in native
      chromatin, we attribute this variation to a dependence of the unraveling force on
      the DNA sequence within individual nucleosomes. The mean force increased from 24
      pN to 31 pN as NaCl was decreased from 100 mM to 5 mM. Spontaneous DNA re
      wrapping events were occasionally observed in real time during force relaxation.
      The observed wide variations in the dynamic force needed to unravel individual
      nucleosomes and the occurrences of sudden DNA re-wrapping events may have an
      important regulatory influence on DNA-directed nuclear processes, such as the
      binding of transcription factors and the movement of polymerase complexes on
      chromatin.

PMID- 16002090
TI  - Molecular evolution of antibody affinity for sensitive detection of botulinum
      neurotoxin type A.
AB  - Botulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance
      known. Potential use of BoNT as a biothreat agent has made development of
      sensitive assays for toxin detection and potent antitoxin for treatment of
      intoxication a high priority. To improve detection and treatment of botulism,
      molecular evolution and yeast display were used to increase the affinity of two
      neutralizing single chain Fv (scFv) antibodies binding BoNT serotype A (BoNT/A).
      Selection of yeast displayed scFv libraries was performed using methods to select
      for both increased association rate constant (k(on)) and decreased dissociation
      rate constants (k(off)). A single cycle of error prone mutagenesis increased the
      affinity of the 3D12 scFv 45-fold from a K(D) of 9.43x10(-10)M to a K(D) of
      2.1x10(-11)M. Affinity of the HuC25 scFv was increased 37-fold from 8.44x10(-10)M
      to 2.26x10(-11)M using libraries constructed by both random and site directed
      mutagenesis. scFv variable region genes were used to construct IgG for use in
      detection assays and in vivo neutralization studies. While IgG had the same
      relative increases in affinity as scFv, (35-fold and 81-fold, respectively, for
      3D12 and HuC25) higher solution equilibrium binding constants were observed for
      the IgG, with the 3D12 K(D) increasing from 6.07x10(-11)M to 1.71x10(-12)M and
      the HuC25 K(D) increasing from 4.51x10(-11)M to 5.54x10(-13)M. Affinity increased
      due to both an increase in k(on), as well as slowing of k(off). Higher affinity
      antibodies had increased sensitivity, allowing detection of BoNT/A at
      concentrations as low as 1x10(-13)M. The antibodies will also allow testing of
      the role of affinity in in vivo toxin neutralization and could lead to the
      generation of more potent antitoxin.

PMID- 16002091
TI  - RNA helical packing in solution: NMR structure of a 30 kDa GAAA tetraloop
      receptor complex.
AB  - Tertiary interactions are critical for proper RNA folding and ribozyme catalysis.
      RNA tertiary structure is often condensed through long-range helical packing
      interactions mediated by loop-receptor motifs. RNA structures displaying helical
      packing by loop-receptor interactions have been solved by X-ray crystallography,
      but not by NMR. Here, we report the NMR structure of a 30 kDa GAAA tetraloop
      receptor RNA complex. In order to stabilize the complex, we used a modular design
      in which the RNA was engineered to form a homodimer, with each subunit containing
      a GAAA tetraloop phased one helical turn apart from its cognate 11-nucleotide
      receptor domain. The structure determination utilized specific isotopic labeling
      patterns (2H, 13C and 15N) and refinement against residual dipolar couplings. We
      observe a unique and highly unusual chemical shift pattern for an adenosine
      platform interaction that reveals a spectroscopic fingerprint for this motif. The
      structure of the GAAA tetraloop-receptor interaction is well defined solely from
      experimental NMR data, shows minor deviations from previously solved crystal
      structures, and verifies the previously inferred hydrogen bonding patterns within
      this motif. This work demonstrates the feasibility of using engineered homodimers
      as modular systems for the determination of RNA tertiary interactions by NMR.

PMID- 16002092
TI  - Stabilization of the ribosomal protein S6 by trehalose is counterbalanced by the
      formation of a putative off-pathway species.
AB  - The effect of trehalose on folding and stability of the small ribosomal protein
      S6 was studied. Non-disruptive point mutations distributed along the protein
      structure were analyzed to characterize the stabilizing effect of trehalose and
      map the folding pathway of S6. On average, the stability of the wild-type and S6
      mutants increases by 3 kcal/mol M trehalose. Despite the non-specific
      thermodynamic stabilization mechanism, trehalose particularly stabilizes the less
      destabilized mutants. Folding/unfolding kinetics shows clearly that trehalose
      induces the collapse of the unfolded state to an off-pathway intermediate with
      non-native diffuse contacts. This state is similar to the collapsed state induced
      by high concentrations of stabilizing salts, as previously reported. Although it
      leads to the accumulation of this off-pathway intermediate, trehalose does not
      change the compactness of the transition state ensemble. Furthermore, the
      productive folding pathway of S6 is not affected by trehalose as shown by a Phi
      value analysis. The unfolded state ensemble of S6 should be more compact in the
      presence of trehalose and therefore destabilized due to decreased conformational
      entropy. Increased compaction of the unfolded state ensemble might also occur for
      more stable mutants of S6, thus explaining the synergistic effect of trehalose
      and point mutations on protein stabilization.

PMID- 16002093
TI  - Effects of different antipsychotics and the antidepressant mirtazapine on glucose
      transporter mRNA levels in human blood cells.
AB  - A relationship between cell metabolism and the expression of glucose transporters
      (GLUT) has been reported. On the other side, treatment with some antipsychotics
      has been associated with an increased incidence of hyperglycemia and new-onset
      type 2 diabetes. We here examined the effects of different concentrations of the
      conventional antipsychotic haloperidol (400 and 800 microg/ml), of the atypical
      antipsychotics clozapine (100 and 200 microg/ml) and olanzapine (100 and 200
      microg/ml) as well as of the antidepressant mirtazapine (10(-7) mol) on the mRNA
      levels of GLUT1-5 in the human leukemic blood cell line U937 after incubation for
      48 h. After experimental treatment, significant increases were detected by ANOVA
      and appropriate post-hoc tests for mirtazapine in GLUT4 mRNA levels as well as
      for haloperidol 400 and 800 microg/ml, olanzapine 200 microg/ml, and mirtazapine
      in GLUT5 mRNA levels. ANOVAs revealed no statistically significant changes in
      GLUT1-3 and beta-actin mRNA levels. These findings suggest that direct effects of
      psychotropic drugs on cellular GLUT4 and GLUT5 may be involved in the metabolic
      dysfunctions occurring during psychopharmacological treatment.

PMID- 16002094
TI  - Algebraic dependency models of protein signal transduction networks from time
      series data.
AB  - Signal transduction networks are crucial for inter- and intra-cellular signaling.
      Signals are often transmitted via covalent modification of protein structure,
      with phosphorylation/dephosphorylation as the primary example. In this paper, we
      apply a recently described method of computational algebra to the modeling of
      signaling networks, based on time-course protein modification data. Computational
      algebraic techniques are employed to construct next-state functions. A Monte
      Carlo method is used to approximate the Deegan-Packel Index of Power
      corresponding to the respective variables. The Deegan-Packel Index of Power is
      used to conjecture dependencies in the cellular signaling networks. We apply this
      method to two examples of protein modification time-course data available in the
      literature. These experiments identified protein carbonylation upon exposure of
      cells to sub-lethal concentrations of copper. We demonstrate that this method can
      identify protein dependencies that might correspond to regulatory mechanisms to
      shut down glycolysis in a reverse, step-wise fashion in response to copper
      induced oxidative stress in yeast. These examples show that the computational
      algebra approach can identify dependencies that may outline signaling networks
      involved in the response of glycolytic enzymes to the oxidative stress caused by
      copper.

PMID- 16002095
TI  - A finite element study relating to the rapid filling phase of the human
      ventricles.
AB  - During the rapid diastolic filling phase at rest, the ventricles of the human
      heart double approximately in volume. In order to investigate whether the
      ventricular filling pressures measured under physiological conditions can give
      rise to such an extensive augmentation in ventricular volumes, a finite element
      model of the human right and left ventricles has been developed, taking into
      account the nonlinear mechanical behavior and effective compressibility of the
      myocardial tissue. The results were compared with the filling phase of the human
      left ventricle as extrapolated from measurements documented in the literature. We
      arrived at the conclusion that the ventricular pressures measured during the
      rapid filling phase cannot be the sole cause of the rise of the observed
      ventricular volumes. We rather advocate the assumption that further dilating
      mechanisms might be part of ventricular activity thus heralding a multiple
      function of the ventricular muscle body. A further result indicates that under
      normal conditions the influence of the viscoelasticity of the tissue should not
      be disregarded in ventricular mechanics.

PMID- 16002096
TI  - Theoretical study on the body form and swimming pattern of Anomalocaris based on
      hydrodynamic simulation.
AB  - Anomalocarid arthropod is the largest known predatory animal of middle Cambrian.
      Studies on Anomalocaris have been piled up in the past two decades since the
      first reasonable reconstruction had achieved in 1980s. Recent finding of legs
      beneath lobes on Parapeytoia Yunnanensis shows arthropod affinities, however,
      many researchers believe that it must be a powerful swimmer by the use of
      developed lobes. In this work, we investigate swimming behaviour of Anomalocaris
      in water by performing hydrodynamical calculation. As a result of simulation
      using moving particle method possible swimming motion of Anomalocaris is
      obtained. In the computer we can change the morphology from known bauplan of
      Anomalocaris found as fossil record. It makes us possible to discuss on the
      variants of Anomalocaris at the intermediate state of evolution process. Such new
      methodology using computer reveals how and from where Anomalocaris evolved.

PMID- 16002097
TI  - G-protein beta-3 subunit gene C825 T polymorphism: influence on plasma sodium and
      potassium concentrations in essential hypertensive patients.
AB  - The C825T polymorphism of the beta-3 subunit of the protein G (GNB3) has been
      related to an increased activity of the Na+/H+ exchanger (NHE-1) through the
      synthesis of an anomalous hyperactive protein. Because of the important role of
      this system in essential hypertension (EH), we analysed the distribution of the
      different genotypes of this polymorphism in normotensive subjects (NS) and
      essential hypertensive patients (EHP), their relationship with the condition of
      salt sensitivity, plasma sodium and potassium concentrations and plasma renin
      activity (PRA) in EHP. 144 subjects (78 EHP and 76 NS) were studied. Salt
      sensitivity was assessed by the rapid protocol of Weinberger and genotype
      determination for GNB3 C825T polymorphism was performed by PCR. The distribution
      of the different genotypes was similar among EHP (CC 37.2%; CT 41.1%; TT 16.7%)
      and NS (CC 32.9%; CT 55.3%; TT 11.8%). In regard to general characteristics of
      EHP (including blood pressure levels) and the condition of salt sensitivity,
      there were no differences among the different genotypes. Plasma sodium
      concentration was higher and plasma potassium was lower in TT patients (141.0+/
      1.7 and 3.7+/-0.1) than in CC patients (139.1+/-1.9 and 4.0+/-0.3) p<0.05. CT
      patients had intermediate values (139.9+/-1.9 and 3.9+/-0.2). PRA values were
      similar in the three genotypes as were the rest of analytical parameters studied.
      Our data demonstrate an association between the C825T polymorphism of the GNB3
      and plasma sodium and potassium concentrations in EHP, as expression of an
      increase in NHE-1 activity, without modifications in PRA nor relationship with
      salt sensitivity.

PMID- 16002098
TI  - The potential role of sigma-1 receptors in lipid transport and lipid raft
      reconstitution in the brain: implication for drug abuse.
AB  - The brain is highly enriched in lipids. However, the molecular biological roles
      of lipids in the brain have been largely unexplored. Although, in 1990s, several
      studies have demonstrated the roles of lipids in a variety of neuronal functions
      and certain neurological diseases, the involvement of lipids in drug dependence,
      if any, is almost totally unknown. Sigma-1 receptors are brain-enriched proteins
      that interact with psychostimulants such as cocaine and methamphetamine. Sigma-1
      receptors possess a putative sterol-binding pocket and are predominantly
      expressed on the endoplasmic reticulum (ER) where most lipids and their
      precursors are synthesized. Sigma-1 receptors are involved in drug-seeking
      behaviors and in psychostimulant-induced behavioral sensitization. Recent studies
      demonstrated that sigma-1 receptors target the lipid-storing subcompartments of
      the ER and are colocalized with cholesterol and neutral lipids. Sigma-1 receptors
      form detergent-insoluble lipid microdomains (lipid rafts) on the ER
      subcompartments and can translocate on the ER when stimulated. Upregulation of
      sigma-1 receptors affect the levels of plasma membrane lipid rafts by changing
      the lipid components therein. The membrane reconstitution thus induced by sigma-1
      receptors in turn affects functions of proteins residing in plasma membrane lipid
      rafts including tropic factor receptors and tyrosine kinases. Specifically, we
      recently found that sigma-1 receptors modulate MAP kinase activation induced by
      tropic factors, neuritegenesis and oligodendrocyte differentiation-all related to
      lipid raft reconstitution. Sigma-1 receptors may thus play a role in
      psychostimulant-induced long-lasting morphological changes in the brain via the
      capacity of sigma-1 receptors in regulating ER lipid transport and the resultant
      plasma membrane lipid raft reconstitution.

PMID- 16002099
TI  - Access to exercise and its relation to cardiovascular health and gene expression
      in laboratory animals.
AB  - The interaction between genes and environment can influence cardiovascular
      disease (CVD). This 16 month study investigated if genes associated with
      cardiovascular (CV) regulation were expressed differently in animals having: 1)
      no access to physical activity or exercise (SED), 2) access to hour-long, twice
      weekly activity (PA), and 3) access every-other-day to a running wheel (EX). Out
      of 31,000 genes, a CV subset comprising 44 genes was investigated. Ten genes from
      this subset were expressed differently in EX compared with SED, and 34 genes were
      expressed differently in PA compared with SED (p<0.05). Total cholesterol (70+/-8
      vs. 101+/-9 mg dl(-1)), triglycerides (104+/-8 vs. 127+/-4 mg dl(-1)), resting
      systolic blood pressure (130+/-3 vs. 141+/-3 mmHg), mean arterial pressure (110+/
      2 vs. 120+/-2 mmHg) and heart rate (380+/-6 vs. 405+/-9 beats min(-1)) were lower
      in EX compared with SED (p<0.05), but intracellular adhesion molecule levels did
      not differ among groups. Mean gene expressions for Gja1, Fdft1, Edn1, Cd36, and
      Hmgb2 differed in animals according to access to physical activity. These genes
      play roles in heart rate, cholesterol biosynthesis, blood pressure, cell
      adhesion, and transcription and neurogenesis regulation, respectively. In
      conclusion, a total of 44 CV genes were expressed differently in SED compared to
      PA and EX; and SED showed more physiological evidence of CVD.

PMID- 16002100
TI  - Effect of intracellular delivery of energy metabolites on intracellular Ca2+ in
      mouse islets of Langerhans.
AB  - Regulation of glucose-induced oscillations in intracellular Ca2+ concentration
      ([Ca2+]i) was investigated by using a novel technique, electroporation from an
      electrolyte-filled capillary, to deliver energy metabolites to the intracellular
      compartment of mouse islets. Intracellular application of ATP resulted in a
      nifedipine-sensitive increase in [Ca2+]i, consistent with a KATP-channel
      dependent mechanism of Ca2+ influx. [Ca2+]i in islets exposed to 10 mM glucose
      oscillated with a period of approximately 3 min, often superimposed with faster
      oscillations. Electroporation of ATP blocked all types of oscillations and
      elevated [Ca2+]i while delivery of ADP had no effect on oscillations.
      Intracellular delivery of glucose-6-phosphate or fructose-1,6-bisphosphate tended
      to transform slow oscillations to fast oscillations. These results demonstrate
      that modulation of ATP concentrations and glycolytic flux are important in
      development of slow oscillations.

PMID- 16002101
TI  - Genomic instability and cancer: networks involved in response to DNA damage.
AB  - A new approach to cancer and new methods in examining rare human chromosome
      breakage syndromes have brought to light complex interactions between different
      pathways involved in damage response, cell cycle checkpoint control and DNA
      repair. The genes affected in these different syndromes are involved in networks
      of processes that respond to DNA damage and prevent chromosomal aberrations
      during the cell cycle. The genes involved include the ATM, ATR, FA-associated
      genes, NBS1 and the cancer susceptibility genes BRCA1 and BRCA2. Chromosomal
      instability is a common feature of many human cancers and most of the instability
      syndromes, characterized by sensitivity to different types of DNA damage, also
      show increased cancer susceptibility. Better understanding of these syndromes and
      their links with familial cancer provide new insight into associations between
      defects in DNA damage response, cell cycle control, DNA repair and cancer.
      Understanding the damage response repair networks that these studies are
      revealing will have important implications for the development of cancer
      management and treatment.

PMID- 16002102
TI  - Feeding and locomotion responses to centrally injected nociceptin/orphanin FQ in
      chicks.
AB  - Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid receptor-like
      receptor or nociceptin receptor (NOP), has been shown to induce feeding,
      locomotion, anti-stress and anxiolytic effects in rodents after central nervous
      system injection. In this study, the effect of intracerebroventricular (icv)
      injection of N/OFQ on feeding and locomotion behavior was evaluated in male
      broiler-type chickens. The icv injection of N/OFQ caused a moderate but
      significant increase in feed intake similar to the classical opioid peptides in
      rats. It also increased feed pecking frequency and feeding time 1 h after
      injection. Stepping, wing flapping and preening were not affected by N/OFQ. These
      results suggest that N/OFQ can act within the central nervous system of chickens
      to increase feed intake.

PMID- 16002103
TI  - Effects of apomorphine on rat behavior in the elevated plus-maze.
AB  - It has been reported that novelty may evoke both an exploratory and a fear drive,
      thus generating behavior responding to an approach/avoidance conflict. However,
      not much is known about the approach component. Whereas there exists abundant
      evidence referring to the avoidance component as the main target for the
      anxiolytic action of benzodiazepines, the involvement of dopaminergic mechanisms
      in fear and anxiety is controversial. The present study examined the effects of
      the dopaminergic agonist apomorphine, the D(2) dopaminergic antagonist sulpiride
      and the combined treatment sulpiride plus apomorphine on conventional and non
      conventional measures of the behavior of rats exposed to an elevated plus-maze.
      Systemic injection of apomorphine (0.25, 0.5 and 1.0 mg/kg) caused a selective
      increase in the time spent in the open arms and in the open arm extremities. Pre
      treatment with sulpiride blocked these effects while this dopaminergic antagonist
      had no effect by its own. Apomorphine produced no significant effects on
      stretching, flat-back-approach or scanning. Therefore, apomorphine increased the
      behavioral response linked to the approach component of the conflict without
      affecting risk assessment behaviors. These findings suggest that dopaminergic
      mechanisms, probably through D(2) receptors, may also be involved in the
      mediation of the conflict derived from the need of gathering information for
      confirming, identifying and localizing danger and take the appropriate action for
      avoiding the threatening stimuli of the elevated plus-maze. A role for
      dopaminergic mechanisms in the setting up of adaptive responses in a fear
      inducing environment is discussed.

PMID- 16002104
TI  - Is stimulation of carotenoid biosynthesis in arbuscular mycorrhizal roots a
      general phenomenon?
AB  - The identification and quantification of cyclohexenone glycoside derivatives from
      the model legume Lotus japonicus revealed far higher levels than expected
      according to the stoichiometric relation to another, already determined
      carotenoid cleavage product, i.e., mycorradicin. Mycorradicin is responsible for
      the yellow coloration of many arbuscular mycorrhizal (AM) roots and is usually
      esterified in a complex way to other compounds. After liberation from such
      complexes it has been detected in AM roots of many, but not of all plants
      examined. The non-stoichiometric occurrence of this compound compared with other
      carotenoid cleavage products suggested that carotenoid biosynthesis might be
      activated upon mycorrhization even in plant species without detectable levels of
      mycorradicin. This assumption has been supported by inhibition of a key enzyme of
      carotenoid biosynthesis (phytoene desaturase) and quantification of the
      accumulating enzymic substrate (phytoene). Our observations suggest that the
      activation of carotenoid biosynthesis in AM roots is a general phenomenon and
      that quantification of mycorradicin is not always a good indicator for this
      activation.

PMID- 16002105
TI  - Fatty acids from seeds of Pinus pinea L.: composition and population profiling.
AB  - Pinus pinea L. is widely disseminated all over the Mediterranean Basin.
      Qualitatively, P. pinea fatty acid seed composition is identical and typical of
      the genus Pinus. This composition is made of unsaturated oil with several unusual
      polymethylene-interrupted unsaturated fatty acids. Linoleic acid is the major
      fatty acid followed by oleic, palmitic and stearic acids. Quantitatively, for all
      Mediterranean populations, total amounts of fatty acids seem to be fairly
      constant and independent from their origin. When applying principal component
      analysis, it seems that there is not a distinct geographical variability.
      Tunisian populations appear to be integral part of the Mediterranean populations
      without any particular structuring. Taking into account this research and the
      data reported in the literature, we can confirm that P. pinea expresses no
      significant variability. This low genetic diversity revealed by fatty acid
      composition can be explained by anthropogenetic diffusion of genetically
      homogeneous reproductive material as early as the first explorations.

PMID- 16002106
TI  - Lanostane triterpenoids from the inedible mushroom Fomitopsis spraguei.
AB  - Investigation of the methanolic extract of the inedible mushroom Fomitopsis
      spraguei (Polyporaceae) led to the isolation of five lanostane-type triterpenoids
      (1-5): three new compounds named fomitopsins A-C (2-4), and two known compounds,
      quercinic acid C (1) and 3alpha-carboxyacetyl-12beta-hydroxyquercinic acid (5).
      Their structures were determined by 2D NMR, MS, IR, UV spectra, and X-ray
      crystallographic analyses. An X-ray crystal structure analysis of quercinic acid
      C (1) established its stereochemistry as 3R,12R-dihydroxy-24R-methyl-23-oxo-25S
      lanost-8-en-26-oic acid.

PMID- 16002108
TI  - Cyanogenic glycosides and menisdaurin from Guazuma ulmifolia, Ostrya virgininana,
      Tiquilia plicata and Tiquilia canescens.

PMID- 16002107
TI  - Alkaloids from Spathelia excelsa: their chemosystematic significance.
AB  - The methanol extract from the leaves of Spathelia excelsa yielded six alkaloids:
      2-(12-oxo-tridecanyl)-3-methoxy-4-quinolone, 2-(10-hydroxy-10-methyldodecanyl)-3
      methoxy-4-quinolone, 2-(11-hydroxy-11-methyldodecanyl)-3-methoxy-4-quinolone, 2
      (12-hydroxytridecanyl)-3-methoxy-4-quinolone, 7-hydroxy-2-(3-hydroxy-3
      methylbutyl)-4-quinolone and 6-hydroxy-2-(3-hydroxy-3-methylbutyl)-4-quinolone,
      in addition to the known 3-O-beta-d-glucopiranosylsitosterol and (-)-epicatechin.
      The 2-alkyl-4(1H)-quinolones in S. excelsa display strong similarities with those
      in Dictyolomatoideae, which contains several 2-alkyl-4-quinolones. The data
      reported herein thus provide firm support for placing Spathelioideae close to or
      within the Dictyolomatoideae.

PMID- 16002109
TI  - Brain stem auditory potentials evoked by clicks in the presence of high-pass
      filtered noise in dogs.
AB  - This study evaluates the effects of a high-frequency hearing loss simulated by
      the high-pass-noise masking method, on the click-evoked brain stem-evoked
      potentials (BAEP) characteristics in dogs. BAEP were obtained in response to
      rarefaction and condensation click stimuli from 60 dB normal hearing level (NHL,
      corresponding to 89 dB sound pressure level) to wave V threshold, using steps of
      5 dB in eleven 58 to 80-day-old Beagle puppies. Responses were added, providing
      an equivalent to alternate polarity clicks, and subtracted, providing the
      rarefaction-condensation potential (RCDP). The procedure was repeated while
      constant level, high-pass filtered (HPF) noise was superposed to the click. Cut
      off frequencies of the successively used filters were 8, 4, 2 and 1 kHz. For each
      condition, wave V and RCDP thresholds, and slope of the wave V latency-intensity
      curve (LIC) were collected. The intensity range at which RCDP could not be
      recorded (pre-RCDP range) was calculated. Compared with the no noise condition,
      the pre-RCDP range significantly diminished and the wave V threshold
      significantly increased when the superposed HPF noise reached the 4 kHz area.
      Wave V LIC slope became significantly steeper with the 2 kHz HPF noise. In this
      non-invasive model of high-frequency hearing loss, impaired hearing of
      frequencies from 8 kHz and above escaped detection through click BAEP study in
      dogs. Frequencies above 13 kHz were however not specifically addressed in this
      study.

PMID- 16002110
TI  - Severe leukopenia and liver biochemistry changes in adult rabbits after
      calicivirus infection.
AB  - Calicivirus infection is the major cause of the severe decrease in the stocks of
      wild and farm rabbits that has occurred worldwide during the last two decades.
      Adult rabbits (10-weeks-old) were experimentally infected with a calicivirus
      inoculum that killed all animals by causing rabbit haemorrhagic disease (RHD)
      within 24-62 h of infection. The rabbits were used to evaluate blood cell numbers
      and serum biochemistry every 6h, starting 12h after the inoculation of the
      caliciviruses. No significant changes in blood parameters were observed in most
      of the rabbits up to 18 h of infection. Severe leukopenia was seen 6h before
      death of the infected rabbits; both heterophils and lymphocytes contributed to
      the decrease in circulating white blood cells. Platelets were also severely
      decreased in number. Marked enhancement in liver enzymes was seen 6-12 h before
      death of the infected rabbits. There was also evidence both for cholestasis, as
      expressed by the elevated levels of direct (conjugated) bilirubin, and for
      hypoglycemia, an alteration that it is likely to contribute for the seizures that
      rabbits show during the late stages of RHD. Liver ultrastructure of rabbits that
      died from RHD revealed extensive hepatocyte vacuolization, severe changes in
      mitochondrial structure, and depletion of glycogen granules. We conclude that:
      (i) severe leukopenia characterizes the final hours of calicivirus-induced RHD;
      (ii) hypoglycemia and cholestasis precede death of rabbits from RHD; (iii) the
      kinetics of liver enzymes allows an accurate prediction of the time of death of
      rabbits from calicivirus-induced RHD.

PMID- 16002111
TI  - Faecal thiaminase, plasma lactate and pyruvate concentrations and erythrocyte
      transketolase activity changes in apparently normal replacement ewes after the
      initiation to the pasture.
AB  - A study was made to investigate faecal thiaminase and the thiamine-related
      biochemical changes in apparently normal replacement ewes with a feed change,
      after the initiation without adaptation to the new pasture. Twenty-four female
      ewes were divided into two groups. Group A was managed in a system based on
      pasture and was compared with group B system based on a diet of concentrate and
      straw until moving to pasture 9 weeks after. Blood samples for lactate, pyruvate
      and erythrocyte transketolase activity determinations and faeces for thiaminase
      estimation were evaluated chronologically. At the end of a 126 days experimental
      period, live weights of groups were similar. We confirmed that clinically normal
      sheep may have thiaminase activity in the faeces and concluded that the
      thiaminase release increased during the diet changes, from concentrate to
      pasture, and that their continued excretion could develop some degree of thiamine
      deficiency.

PMID- 16002112
TI  - Gas chromatography-mass spectrometric analysis of oxidative reactions of [19,19
      (2)H(2)]19-hydroxy-3-deoxy androgens by placental aromatase. bsence of a
      deuterium-isotope effect.
AB  - Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of
      androst-4-ene-3,17-dione (AD) to estrone through three sequential oxidations of
      the 19-methyl group. 3-DeoxyAD (1) and its 5-ene isomer 4 are potent and good
      competitive aromatase inhibitors, which are converted by aromatase to the
      aldehyde derivatives 3 and 6, respectively, through 19-hydroxy intermediates 2
      and 5, respectively. To study the deuterium isotope effect on the conversions of
      19-ols 2 and 5 into the corresponding 19-als 3 and 6, we initially synthesized
      [19,19-(2)H(2)]19-ols 2 and 5 starting from the corresponding non-labeled 19-als
      3 and 6 through NaB(2)H(4) reduction of the 19-aldehyde group, followed by
      oxidation with pyridinium dichromate, and a subsequent NaB(2)H(4) reduction.
      Approximately 1:1 mixtures of non-labeled (d(0)) and deuterated (d(2)) 19-ols 2
      and 5 were separately incubated with human placental microsomes in the presence
      of NADPH under an air atmosphere, and deuterium contents of the recovered
      substrates and the 19-aldehyde products were determined by gas chromatography
      mass spectrometry. In each experiment, the ratio of d(0) to d(2) of the recovered
      substrate along with that of d(0) to d(1) of the product were identical to the
      d(0) to d(2) ratio of the employed substrate irrespective of the incubation time,
      indicating that the 19-oxygenations of the 3-deoxy steroids 2 and 5 proceeded
      without a detectable isotope effect, as seen in the aromatization sequence of the
      natural substrate AD.

PMID- 16002113
TI  - The development and identification of constructing tissue engineered bone by
      seeding osteoblasts from differentiated rat marrow stromal stem cells onto three
      dimensional porous nano-hydroxylapatite bone matrix in vitro.
AB  - The purposes of this study were to develop a new cultural method for the rat bone
      marrow stromal cells (MSCs) to differentiate into osteoblasts well in vitro, and
      to investigate the feasibility of using MSCs as seed cells and three-dimensional
      porous nano-hydroxylapatite as scaffolds for constructing tissue-engineered bone.
      MSCs of rats were isolated, cultured, induced to differentiate into osteoblasts,
      and then observed with inverted microscopy. Histochemical staining and radio
      immunological analysis were applied for identifying MSCs. Whereafter MSCs were
      seeded onto three-dimensional porous nano-hydroxylapatite scaffolds, and scanning
      electron microscopy was applied to evaluate their growth on scaffolds. Results
      showed that MSCs were typical fibroblast-like and possessed a better
      proliferating capability; the activity of alkaline phosphatase (ALP) and the
      secretion of osteocalcin of MSCs were produced gradually and increased
      continuously; the cells seeded on three-dimensional porous nano-hydroxylapatite
      scaffolds adhered, proliferated and differentiated well. These results
      demonstrated that the new improved culture method had the advantages of short
      isolating time, less risk of contamination and higher efficiency and accordingly
      was conducive to MSCs proliferating and differentiating into osteoblasts, and
      that it was advantageous to constructing tissue-engineered bone using MSCs as
      seed cells and three-dimensional porous nano-hydroxylapatite as scaffolds.

PMID- 16002114
TI  - Extracting meaning from functional genomics experiments.
AB  - The completion of draft genome sequences for human, mouse, rat, and an increasing
      number of other species, has provided us with preliminary gene catalogues for
      many organisms of medical and scientific interests. Interpreting these gene lists
      in the context of the organism's underlying biology, however, remains difficult.
      The development of DNA microarrays provided one potential source of data to help
      interpret gene function; by profiling global patterns of gene expression across
      diverse conditions, it was hoped that we might be able to develop insight into
      biological function. But the power of these functional genomics assays, as well
      as assays in proteomics and metabolomics, is that they primarily give us lists of
      differentially expressed genes that can be correlated with particular phenotypic
      states, but which remain difficult to link mechanistically to the biology driving
      the phenotype.

PMID- 16002115
TI  - Interdisciplinary neurotoxicity inhalation studies: carbon disulfide and carbonyl
      sulfide research in F344 rats.
AB  - Inhalation studies were conducted on the hazardous air pollutants, carbon
      disulfide, which targets the central nervous system (spinal cord) and peripheral
      nervous system (distal portions of long myelinated axons), and carbonyl sulfide,
      which targets the central nervous system (brain). The objectives were to
      investigate the neurotoxicity of these compounds by a comprehensive evaluation of
      function, structure, and mechanisms of disease. Through interdisciplinary
      research, the major finding in the carbon disulfide inhalation studies was that
      carbon disulfide produced intra- and intermolecular protein cross-linking in
      vivo. The observation of dose-dependent covalent cross-linking in neurofilament
      proteins prior to the onset of lesions is consistent with this process
      contributing to the development of the neurofilamentous axonal swellings
      characteristic of carbon disulfide neurotoxicity. Of significance is that valine
      lysine thiourea cross-linking on rat globin and lysine-lysine thiourea cross
      linking on erythrocyte spectrin reflect cross-linking events occurring within the
      axon and could potentially serve as biomarkers of carbon disulfide exposure and
      effect. In the carbonyl sulfide studies, using magnetic resonance microscopy
      (MRM), we determined that carbonyl sulfide targets the auditory pathway in the
      brain. MRM allowed the examination of 200 brain slices and made it possible to
      identify the most vulnerable sites of neurotoxicity, which would have been missed
      in our traditional neuropathology evaluations. Electrophysiological studies were
      focused on the auditory system and demonstrated decreases in auditory brain stem
      evoked responses. Similarly, mechanistic studies focused on evaluating cytochrome
      oxidase activity in the posterior colliculus and parietal cortex. A decrease in
      cytochrome oxidase activity was considered to be a contributing factor to the
      pathogenesis of carbonyl sulfide neurotoxicity.

PMID- 16002116
TI  - Single nucleotide polymorphism in transcriptional regulatory regions and
      expression of environmentally responsive genes.
AB  - Single nucleotide polymorphisms (SNPs) in the human genome are DNA sequence
      variations that can alter an individual's response to environmental exposure.
      SNPs in gene coding regions can lead to changes in the biological properties of
      the encoded protein. In contrast, SNPs in non-coding gene regulatory regions may
      affect gene expression levels in an allele-specific manner, and these functional
      polymorphisms represent an important but relatively unexplored class of genetic
      variation. The main challenge in analyzing these SNPs is a lack of robust
      computational and experimental methods. Here, we first outline mechanisms by
      which genetic variation can impact gene regulation, and review recent findings in
      this area; then, we describe a methodology for bioinformatic discovery and
      functional analysis of regulatory SNPs in cis-regulatory regions using the
      assembled human genome sequence and databases on sequence polymorphism and gene
      expression. Our method integrates SNP and gene databases and uses a set of
      computer programs that allow us to: (1) select SNPs, from among the >9 million
      human SNPs in the NCBI dbSNP database, that are similar to cis-regulatory element
      (RE) consensus sequences; (2) map the selected dbSNP entries to the human genome
      assembly in order to identify polymorphic REs near gene start sites; (3)
      prioritize the candidate polymorphic RE containing genes by searching the
      existing genotype and gene expression data sets. The applicability of this system
      has been demonstrated through studies on p53 responsive elements and is being
      extended to additional pathways and environmentally responsive genes.

PMID- 16002117
TI  - Role of RNA structures present at the 3'UTR of dengue virus on translation, RNA
      synthesis, and viral replication.
AB  - We have developed a dengue virus replicon system that can be used to discriminate
      between translation and RNA replication. Using this system, we analyzed the
      functional role of well-defined RNA elements present at the 3'UTR of dengue virus
      in mammalian and mosquito cells. Our results show that deletion of individual
      domains of the 3'UTR did not significantly affect translation of the input RNA
      but seriously compromised or abolished RNA synthesis. We demonstrated that
      complementarity between sequences present at the 5' and 3' ends of the genome is
      essential for dengue virus RNA synthesis, while deletion of domains A2 or A3
      within the 3'UTR resulted in replicons with decreased RNA amplification. We also
      characterized the vaccine candidate rDEN2Delta30 in the replicon system and found
      that viral attenuation is caused by inefficient RNA synthesis. Furthermore, using
      both the replicon system and recombinant viruses, we identified an RNA region of
      the 3'UTR that enhances dengue virus replication in BHK cells while is
      dispensable in mosquito cells.

PMID- 16002118
TI  - The toxic potential of an industrial effluent determined with the Saccharomyces
      cerevisiae-based assay.
AB  - Increasing levels of environmental pollution and the continuous monitoring of
      water quality both request specific and sensitive methods for the detection of
      detrimental water contents. On a regulatory basis genotoxicity is assessed by the
      standard umu-test (ISO 13829) that responds to DNA damage induced by chemicals.
      The focus of this study was the examination of the toxic potential of samples
      taken from the wastewater treatment plant of a refinery factory to explore the
      applicability of the Saccharomyces cerevisiae (bakers yeast) test for the
      detection of bio-available genotoxic activity in complex matrices. The toxic
      potential of samples without pre-treatment and following centrifugation was
      determined with the eukaryotic Saccharomyces cerevisiae bioassay based on the
      transcriptional activation of the green fluorescent protein (gfp) fused to the
      DNA damage inducible RAD54 promoter and general growth inhibition. Primary
      effluent samples were taken as qualified sterile spot samples from the final
      effluent of the purification plant. The Saccharomyces cerevisiae assay yielded
      geno- and cytotoxic responses in all complex untreated and centrifuged samples
      with high reproducibility. The obtained results suggest that the yeast assay is
      suited as a screening tool to monitor genotoxic potential of wastewater.

PMID- 16002119
TI  - Displacement of five metals sorbed on kaolinite during treatment with modified
      Fenton's reagent.
AB  - The displacement of sorbed metals during the treatment of soils and groundwater
      with modified Fenton's reagent was investigated using five common metal
      contaminants (cadmium, copper, lead, nickel, and zinc) and kaolinite as a model
      sorbent. Modified Fenton's conditions included three H(2)O(2) concentrations
      (0.9, 1.8, 2.7 M) and two catalysts: soluble iron (III) at pH 3 and iron (III)
      NTA chelate at pH 6. Iron (III)-catalyzed Fenton's reactions released significant
      amounts of zinc, cadmium, and copper. Modified Fenton's reactions catalyzed by
      iron (III)-NTA released zinc, cadmium, copper, and lead, and resulted in greater
      amounts of metals release than the iron (III)-catalyzed reactions. Metals release
      may have been mediated by transient oxygen species, such as superoxide, generated
      by propagation reactions, which become dominant at the relatively high hydrogen
      peroxide concentrations used. Metals release from kaolinite was undetectable when
      sufficiently low hydrogen peroxide concentrations were maintained to minimize
      propagation reactions. These results indicate that using dilute concentrations of
      hydrogen peroxide for Fenton's ISCO may minimize potential metals mobility when
      treating contaminated soils and groundwater containing a mixture of organic and
      metal contaminants.

PMID- 16002120
TI  - Typology of diatom communities and the influence of hydro-ecoregions: a study on
      the French hydrosystem scale.
AB  - By comparing diatom communities in natural and disturbed sites, indicators for
      different types and levels of anthropogenic disturbance can be found. As a first
      step, this study aims to describe the different natural and disturbed community
      types found throughout the French hydrosystem. 836 diatom samples were analysed
      with an unsupervised neural network, the self-organising-map, a well accepted
      method for community ordination. 11 different communities were identified, 5
      corresponding to non-impacted or slightly impacted conditions and representing
      the diatom natural variability of our dataset. These 5 communities corresponded
      to 5 different hydro-ecoregions, i.e. 5 river types with similar geological
      context and range in altitude. The 6 other communities were typical of rivers
      under anthropogenic pressure. The influence of natural conditions within the
      hydro-ecoregions was overwhelmed by the nature and the intensity of the pollution
      at the sampling stations. This work was done in the context of the application
      and enforcement of the Water Framework Directive.

PMID- 16002121
TI  - Studies on removal of metal ions and sulphate reduction using rice husk and
      Desulfotomaculum nigrificans with reference to remediation of acid mine drainage.
AB  - The utility of rice husk as an adsorbent for metal ions such as iron, zinc and
      copper from acid mine water was assessed. The adsorption isotherms exhibited
      Langmuirian behavior and were endothermic in nature. The free energy values for
      adsorption of the chosen metal ions onto rice husk were found to be highly
      negative attesting to favorable interaction. Over 99% Fe(3+), 98% of Fe(2+) and
      Zn(2+) and 95% Cu(2+) uptake was achieved from acid mine water, with a
      concomitant increase in the pH value by two units using rice husk. The
      remediation studies carried out on acid mine water and simulated acid mine water
      pretreated with rice husk indicated successful growth of Desulfotomaculum
      nigrificans (D. nigrificans). The amount of sulphate bioreduction in acid mine
      water at an initial pH of 5.3 was enhanced by D. nigrificans from 21% to 40% in
      the presence of rice husk filtrate supplemented with carbon and nitrogen. In
      simulated acid mine water with fortified husk filtrate, the sulphate reduction
      was even more extensive, with an enhancement to 73%. Concurrently, almost 90%
      Fe(2+), 89% Zn(2+) and 75% Cu(2+) bioremoval was attained from simulated acid
      mine water. Metal adsorption by rice husk was confirmed in desorption experiments
      in which almost complete removal of metal ions from the rice husk was achieved
      after two elutions using 1M HCl. The possible mechanisms of metal ion adsorption
      onto rice husk and sulphate reduction using D. nigrificans are discussed.

PMID- 16002122
TI  - Dechlorination of trichloroethylene by a steel converter slag amended with
      Fe(II).
AB  - This study aims to assess the feasibility of using slag, byproduct from iron and
      steel making industries, as a new reactive material for dechlorination reactions
      and to investigate dechlorination chemistries of the systems containing the slag
      and Fe(II). Initially, screening experiments were conducted to evaluate various
      systems containing slags with or without Fe(II). A combination of the steel
      converter slag and Fe(II) showed a potential to be developed as a reactive
      material to treat chlorinated organics. Further kinetic studies with the steel
      converter slag/Fe(II) systems revealed that the dechlorination capacity of the
      slag/Fe(II) system is comparable to that of zero-valent iron and generally higher
      than the cement/Fe(II) system. The slag/Fe(II) system can substantially
      dechlorinate trichloroethylene (TCE) in the neutral pH region, although the
      dechlorination rate was greatest in the pH region between 12 and 13. TCE
      reductions in the slag/Fe(II) system were observed to occur through reductive
      beta-elimination pathways that produce primarily acetylene and no chlorinated
      intermediates such as vinyl chloride. These results demonstrate that the steel
      converter slag with Fe(II) has sound characteristics for an alternative reactive
      medium for subsurface remediation.

PMID- 16002123
TI  - A QSAR study of acute toxicity of N-substituted fluoroacetamides to rats.
AB  - Acute toxicity in vivo toward rats, of nineteen N-alkyl and N-cycloalkyl
      fluorocetamides [F-CH(2)-C(O)-NH-R] was correlated with their structure-dependent
      properties. Used descriptors are: molecular weights (M(w)) and heat of formation
      (DeltaH(f)) of compounds; molar refractivity (CMR), lipophilicity (ClogP), Broto
      lipol values, virtual logP, molecular lipophilic potential (MLP), Van der Waals
      surfaces (VdW SAS) and hydropathicity surface (ILM) of whole molecules; Taft
      steric parameters (E(s)); E(s) values with Hancock corrections (E(s)(CH)) and
      Verloop sterimol (B(5)) and (L) parameters of alkyl and cycloalkyl residues;
      superdelocalizabilities and electron densities on the [NH-C(O)-CH(2)-F] fragment.
      Strong quantitative structure-activity relationships were assessed. Obtained
      correlation suggested that lipophilicity, shape and bulkiness of the alkyl and
      cycloalkyl substituents, particular nearest vicinity of the amide nitrogen, as
      well charges on the amide moiety are the main factors that influence on the acute
      toxicity of studied compounds toward rats. Mechanism of toxic action was
      proposed.

PMID- 16002124
TI  - Mitigation of azinphos-methyl in a vegetated stream: comparison of runoff- and
      spray-drift.
AB  - The effectiveness of aquatic macrophytes in reducing runoff- and spray-drift
      induced azinphos-methyl (AZP) input was compared in a vegetated stream. Water,
      sediment and plant samples were taken at increasing distances from a point of
      input during a spray-drift event and two runoff (10 and 22 mm/day) events. Peak
      concentrations of AZP decreased significantly (R2=0.99; p<0.0001; n=5) from 0.24
      microg/l to 0.11 microg/l during the 10mm runoff event. No reduction took place
      during the 22 mm event. AZP concentrations were reduced by 90% following spray
      drift input, with peak concentrations decreasing significantly (R2=0.93;
      p=0.0084; n=5) from 4.3 microg/l to 1.7 microg/l with increasing distance from
      the point of input. Plant samples taken after the spray-drift event showed
      increased AZP concentrations in comparison to before the event indicating
      sorption of the pesticide to the macrophytes. Although peak concentrations of AZP
      were as effectively mitigated during the 10mm runoff event as during the spray
      drift event, predictive modelling revealed that maximum concentrations expected
      during a worst-case scenario 10mm runoff event (0 days after application) are an
      order of magnitude lower than what can be expected for a worst-case spray-drift
      and 22 mm runoff event, suggesting that spray-drift-derived pesticide
      concentrations are more effectively mitigated than those of runoff.

PMID- 16002125
TI  - Aging of air pollution control residues from municipal solid waste incinerator:
      role of water content on metal carbonation.
AB  - This work studies the effect of water content on the aging of APC residues, with
      a liquid to solid ratio (L/S) of 0.25 or 10, aged with or without exposure to
      ambient air. After the residue was mixed with water, CaSO4 and
      (Na,K)Al3(SO4)2(OH)6 in the raw sample yielded ettringite. When CO2 were
      available, this ettringite was further transformed to gypsum, calcite and
      possibly gibbsite. Experimental data revealed that the concentrations of Pb, Zn,
      Cd, Hg, and Cu fell with age, whereas that of Cr increased. Given L/S=10, excess
      Ca2+ ions were present in the suspension, so a precipitate of primarily calcite
      crystals of sizes under 5 microm formed on the air-water surface. This layer
      significantly reduced the rates of decline of Pb, Zn, Cd and Hg contents, and
      also reduced the increasing rate of Cr content in the suspension. This result
      follows from the mass transfer barrier of CO2 added at the air-water surface and
      the occurrence of subsequent chemical reactions in the suspension. An estimate of
      the mass transfer rate revealed that the rate-controlling step with L/S=10 was
      the dissolution and diffusion of CO2 in the bulk solution. However, at L/S=0.25,
      the rate-limiting step was the dissolution of metals from ash particles. Water
      content is a very important process factor, whose distribution in the sample, and
      the resulting competition between carbonate ion flux and heavy metal flux, govern
      the reaction time required during the natural aging process.

PMID- 16002126
TI  - The post-thrombotic syndrome after upper extremity deep venous thrombosis in
      adults: a systematic review.
AB  - BACKGROUND: Post-thrombotic syndrome is a chronic, potentially debilitating
      complication of deep vein thrombosis (DVT) of the lower extremity. Comparatively
      little is known about post-thrombotic syndrome after upper extremity DVT (UEDVT).
      OBJECTIVE: To perform a systematic review of clinical studies that have examined
      the incidence, clinical features, risk factors and management of post-thrombotic
      syndrome after UEDVT. METHODS: Using combinations of keywords venous thrombosis,
      postphlebitic syndrome, thrombophlebitis, arm swelling, post-thrombotic syndrome,
      UEDVT, Paget-Schroetter syndrome, thoracic outlet syndrome, axillary vein,
      subclavian vein, and central venous catheter, the MEDLINE database was searched
      for English language articles published between January 1967 and December 2004.
      Retrieval and review of articles were restricted to clinical studies in humans
      that described long-term outcomes after objectively confirmed UEDVT. RESULTS:
      Seven studies were reviewed. The frequency of PTS after UEDVT ranges from 7-46%
      (weighted mean 15%). Residual thrombosis and axillosubclavian vein thrombosis
      appear to be associated with an increased risk of PTS, whereas catheter
      associated UEDVT may be associated with a decreased risk. There is currently no
      validated, standardized scale to assess upper extremity PTS, and little consensus
      regarding the optimal management of this condition. Quality of life is impaired
      in patients with upper extremity PTS, especially after DVT of the dominant arm.
      CONCLUSIONS: PTS is a frequent complication of UEDVT, yet little is known
      regarding risk factors and optimal management. A standardized means of diagnosis
      would help to establish better management protocols. The impact of upper
      extremity PTS on quality of life should be further quantified.

PMID- 16002127
TI  - Comparison of electrophysiological models for human ventricular cells and
      tissues.
AB  - In this paper we briefly review currently published models for human ventricular
      cells and tissues. We discuss the Priebe-Beuckelmann (PB) model and the reduced
      version of this model constructed by Bernus et al. (redPB), the Ten Tusscher
      Noble-Noble-Panfilov (TNNP) model and the Iyer-Mazhari-Winslow (IMW) model. We
      compare several characteristics of these models such as: sources of experimental
      data the models are based on, action potential morphology, action potential
      duration (APD) and conduction velocity (CV) restitution and computational
      efficiency. Finally, we discuss the application of a subset of these models-the
      redPB and the TNNP model-to study simulated spiral wave dynamics in 2D tissue
      sheets and in the human ventricles. We discuss the suitability of the different
      models for particular research questions and their limitations.

PMID- 16002128
TI  - Space mediates coexistence of females and hermaphrodites.
AB  - In gynodioecious populations of flowering plants females and hermaphrodites
      coexist. Gynodioecy is widespread and occurs in both asexual and sexual species
      but does not admit a satisfactory explanation from classical sex ratio theory. In
      sexual populations male fertility restoring genes have evolved to counter non
      nuclear male sterility mutations. In pseudogamous asexual populations pollen
      retention and increased self-fertilization can make male sterility costly. Both
      of these mechanisms can promote coexistence. However, it remains unclear how
      either of these mechanisms could evolve if coexistence was not initially
      possible. In the absence of these adaptations non-spatial models predict that
      females either fail to invade hermaphrodite populations or else displace them
      until pollen shortage drives the population to extinction. We develop a pair
      approximation to a probabilistic cellular automata model in which females and
      hermaphrodites interact on a regular lattice. The model features independent
      pollination and colonization processes which take place on different timescales.
      The timescale separation is exploited to obtain, with perturbation methods, a
      more manageable aggregated pair approximation. We present both the mean field
      model which recreates the classical non-spatial predictions and the pair
      approximation, which strikingly predicts different invasion criteria and
      coexistence under a wide range of parameters. The pair approximation is shown to
      correspond well qualitatively with simulation behaviour.

PMID- 16002129
TI  - Sperm concentration determination between hemacytometric and CASA systems: why
      they can be different.
AB  - Determination of sperm concentration is a critical component of semen analysis.
      Traditionally, the hemacytometer has been the standard for calibrating other
      technologies used to estimate sperm concentration, including photometry, Coulter
      counters, flow cytometry, and computer-automated semen analysis (CASA).
      Disposable capillary-loaded slides are commonly used in conjunction with most
      CASA systems currently in use. Questions have been raised regarding differences
      in sperm concentration measurements between CASA systems (using 20 microm
      disposable slides) and hemacytometry. This review explains that these differences
      are largely due to the Segre-Silberberg (SS) effect, which occurs during
      Poiseuille flow in thin, capillary-loaded slides. The SS effect can lead to
      errors in estimation of particle concentration, as demonstrated with latex beads
      and suspensions of human or porcine spermatozoa. The SS effect does not appear to
      have time to develop in the hemacytometer, which at 100 microm is considerably
      deeper than most disposable slides. Thus, hemacytometry, when properly performed,
      remains the gold standard for estimation of sperm concentration. When using thin
      (20 microm) slides with CASA systems, recognition of the appropriate compensation
      factor to adjust for the SS effect is critical for accuracy.

PMID- 16002131
TI  - Possibilities with today's reproductive technologies.
AB  - Reproductive efficiency is critical to economic viability for cow/calf producers;
      however, very few producers take advantage of available reproductive technologies
      that can increase profitability. Today, more opportunities are available for
      producers who want to capture value from known genetics. Through the use of
      artificial insemination (AI), the average producer has access to a wide range of
      high-accuracy sires that can be selected to match production goals. Systems to
      synchronize estrus and ovulation can now produce pregnancy rates to a single
      fixed-timed AI that are 10-15% greater than those of the previous generation.
      Increased age and weight of calves at weaning is sufficient in some situations to
      pay for the cost of synchronization and AI. As a result of synchronization, more
      cows calve early the next year and in subsequent years of synchronization. The
      breeding season can be shortened without reducing end-of-season pregnancy rates,
      since synchronized cows have one more chance to conceive than unsynchronized cows
      in a 22-25 day interval. Cow nutrition can be more economically and precisely
      managed with a shorter breeding period. Producers that establish AI programs now
      will be prepared to take advantage of newly identified superior genetics or other
      technologies, e.g. sexed semen, when they become available. Trends towards more
      value-based marketing and improvements in pregnancy rates from synchronization
      systems, make this a key time to be aware of the possibilities using reproductive
      technologies.

PMID- 16002132
TI  - Effect of iodine on mercury concentrations in dental-unit wastewater.
AB  - OBJECTIVE: This study was undertaken to determine whether iodine used to control
      bacteria in dental unit waterlines could increase mercury concentrations in
      dental wastewater. METHODS: The study was conducted in four parts. Part 1.
      Solutions containing iodine in concentrations ranging from zero (control) to 20
      mg/L were mixed with ground and sieved dental amalgam and then allowed to
      equilibrate by settling. Cold vapor atomic absorption spectrometry was used to
      determine mercury levels in the settled supernatants at 24 h and at 7 days. Part
      2. Deionized water was pumped through an iodine-releasing water-treatment
      cartridge, collected, and mixed with ground and sieved dental amalgam. Mercury
      levels in settled supernatants were measured at 24 h and at 7 days. Part 3.
      Iodine in water from two commercial iodine-releasing cartridges was measured
      using Inductively Couple Plasma Mass Spectrometry. Part 4. Baseline mercury
      levels in settled supernatants from wastewater collected from two dental chairs
      were compared to samples taken from chairs equipped with iodine-releasing
      cartridges. RESULTS: Part 1. A linear correlation between iodine and mercury
      concentration (r2=0.9167 and 0.9459, respectively, both P<0.001) was seen at both
      24 h and 7 days. Part 2. Mean mercury levels in 24h samples were 3.0 times higher
      than the controls (0.2864 mg/L compared with 0.0939mg/L for the 24 h controls).
      Mean mercury levels in the 7-day samples were 5.9 times higher than the 7-day
      controls (0.2048 mg/L compared with 0.0348 mg/L for the 7-day controls). Part 3.
      The effluent from two iodine-releasing cartridges showed iodine concentrations
      averaging 3.2 mg/L (n=10, SD=0.8, range=2.5-4.6). Part 4. Data from the clinical
      study showed a statistically significant 2.5-fold increase in mercury levels with
      iodine-containing samples compared to baseline (0.0853 mg/L, n=18, SD=0.0441 and
      0.0345 mg/L, n=18, SD=0.0145, respectively; P<0.001). SIGNIFICANCE: Data suggest
      that iodine can increase concentrations of dissolved mercury in dental unit
      wastewater.

PMID- 16002133
TI  - Effect of fiber volume fraction and length on the wear characteristics of glass
      fiber-reinforced dental composites.
AB  - OBJECTIVE: The main objective of this study was to evaluate the wear
      characteristics of fiber-reinforced dental composites. Variables under
      investigation include the fiber weight percent added to the matrix as well as
      fiber length. METHODS: Dental specimens with glass fiber content of 2, 5.1, 5.7,
      and 7.6 wt% with fiber length of either 1.5 or 3 mm, were prepared by mixing an
      activated dental resin with commercial glass fibers. The specimens were then
      tested on a pin on disc setup, where the antagonist disc was manufactured of a
      similar fiber-reinforced composite with 5.1 wt% fiber and fiber length of 3 mm.
      The volume loss and coefficient of friction of the specimens was monitored
      periodically throughout testing. In addition, the wear surfaces of all specimens
      were evaluated using a scanning electron microscope. RESULTS: The specimens with
      5.7 wt% fibers and fiber length of 3 mm performed better in this study compared
      to all other fiber-reinforced specimens under all load conditions. In fact, this
      specimen had a comparable wear rate to a particle-filled dental composite. For
      the fiber lengths considered, increasing the length of the fibers increased the
      wear resistance of the specimen. The coefficient of friction showed a good
      correlation with the wear resistance of specimens. SIGNIFICANCE: Fiber-reinforced
      composites demonstrated a high resistance to wear and may therefore be
      advantageous for dental applications, where high wear resistance is essential to
      functionality.

PMID- 16002134
TI  - The influence of the cutting speed on bond strength and integrity of microtensile
      specimens.
AB  - OBJECTIVES: To verify the influence of cutting speed during microtensile specimen
      preparation, on bond strength values and on the sample microscopic integrity of a
      single-bottle adhesive system to enamel and dentin. METHODS: Thirty sound human
      third molars were restored with light-cured Excite and Tetric Ceram according to
      manufacturers' instructions, being half in ground enamel [E], and half in flat
      dentin [D]. After 24 h storage in distilled water at 37 degrees C, the restored
      teeth were sectioned in x and y-axes under different cutting speed: 100, 200 or
      400 RPM, obtaining stick shaped specimens with cross-sectional area of 1.0 mm(2).
      Five specimens from each experimental group were randomly selected before being
      loaded for SEM analysis, while the remaining samples were subjected to the
      microtensile bond strength test. Because the variance of dentin specimens was
      significantly higher than the variance of enamel samples, analysis of the
      influence of the cutting speed was performed separately, by substrate. RESULTS:
      The mean values in MPa were calculated including/excluding premature failures:
      E1: 24.67/27.31(a); E2: 24.03/25.81(a); E4: 19.06/21.52(b); D1: 35.80/36.33(A);
      D2: 35.84/36.65(A); D4: 37.78/38.50(A). In the SEM analysis, better integrity of
      the dentin specimens was observed when compared to the enamel samples, for which
      the integrity was greater in the lower cutting speed groups. SIGNIFICANCE: It can
      be concluded that the cutting speed is an important factor that should be
      considered, mainly when enamel is involved, since it may affect the bond strength
      results and the integrity of the specimens.

PMID- 16002135
TI  - The effect of surface chemistry modification of titanium alloy on signalling
      pathways in human osteoblasts.
AB  - Establishing and maintaining mature bone at the bone-device interface is critical
      to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and
      dental implants results in implant failure. Considerable effort has been devoted
      to alter the surface characteristics of these biomaterials in order to improve
      the initial interlocking of the device and skeleton. We investigated the effect
      of surface chemistry modification of titanium alloy (Ti-6Al-4V) with zinc,
      magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation
      of key intracellular signalling proteins in human bone-derived cells (HBDC)
      cultured on these modified Ti-6Al-4V surfaces. Western blotting demonstrated that
      modifying Ti-6Al-4V with CHAP or Mg results in modulation of key intracellular
      signalling proteins. We showed an enhanced activation of Shc, a common point of
      integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway
      was also upregulated, suggesting its role in mediating osteoblastic cell
      interactions with biomaterials. The signalling pathway involving c-fos (member of
      the activated protein-1) was also shown to be upregulated in osteoblasts cultured
      on the Mg and CHAP modified Ti-6Al-4V. Thus surface modification with CHAP or Mg
      may contribute to successful osteoblast function and differentiation at the
      skeletal tissue-device interface.

PMID- 16002136
TI  - Effect of sample geometry on the apparent biaxial mechanical behaviour of planar
      connective tissues.
AB  - Mechanical testing methodologies developed for engineering materials may result
      in artifactual material properties if applied to soft planar connective tissues.
      The use of uniaxial tissue samples with high aspect ratios or biaxial samples
      with slender cruciform arms could lead to preferential loading of only the
      discrete subset of extracellular fibres that fully extend between the grips. To
      test this hypothesis, cruciform biaxial connective tissue samples that display
      distinctly different material properties (bovine pericardium, fish skin), as well
      as model textile laminates with predefined fibrous orientations, were repeatedly
      tested with decreasing sample arm lengths. With mechanical properties determined
      at the sample centre, results demonstrated that the materials appeared to become
      stiffer and less extensible with less slender sample geometries, suggesting that
      fibre recruitment increases with decreasing sample arm length. Alterations in the
      observed shear behaviour and rigid body rotation were also noted. The only truly
      reliable method to determine material properties is through in vivo testing, but
      this is not always convenient and is typically experimentally demanding. For the
      in vitro determination of the biaxial material properties, appropriate sample
      geometry should be employed in which all of the fibres contribute to the
      mechanical response.

PMID- 16002137
TI  - Get a grip: integrins in cell-biomaterial interactions.
AB  - Integrin adhesion receptors have emerged as central regulators of cell
      biomaterial interactions. This opinion paper discusses how integrins control
      cellular and host responses to biomaterials and new strategies to manipulate
      these adhesive interactions in order to elicit specific cellular responses.

PMID- 16002138
TI  - In vitro and in vivo antitumor activity of the NF-kappaB inhibitor DHMEQ in the
      human T-cell leukemia virus type I-infected cell line, HUT-102.
AB  - Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell
      leukemia virus type I (HTLV-I). The NF-kappaB pathway is activated in ATL cells
      and in virus-infected cells, and plays a central role in oncogenesis. We examined
      the effect of the novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin
      (DHMEQ), on a well-characterized HTLV-I-infected cell line, HUT-102, in vitro and
      in vivo. DHMEQ inhibited translocation of NF-kappaB p65 to the nucleus and
      induced apoptotic cell death in vitro. In vivo, DHMEQ inhibited the growth and
      infiltration of HUT-102 tumor cells transplanted subcutaneously in SCID mice
      lacking natural killer cell activity.

PMID- 16002139
TI  - Absorption, distribution, and transformation of TNT in higher plants.
AB  - The ability of eight species of plants to assimilate 2,4,6-trinitrotoluene (TNT)
      was investigated. Glycine max (soybean), in particular, demonstrated rapid
      assimilation of high concentrations of this explosive. Penetration and
      localization of [1-(14)C]-TNT in plant root cells and leaves were studied via
      electron microscopic autoradiography. TNT was shown to be localized primarily on
      membrane structures involved in the transportation of nicotinamide coenzymes
      (membranes of endoplasmic reticulum, mitochondria, plastids). [1-(14)C]-TNT in
      roots was incorporated mainly in low-molecular-weight metabolites; however, in
      stems and leaves, the radiocarbon was incorporated in biopolymers. Enzymatic
      transformation of TNT in roots was studied, and it was found that degradation
      involved mainly nitroreductase acting on the TNT nitro groups. The process was
      intensified in the presence of electron donors--NADH and NADPH. Nitroreductase
      activity was revealed in root cell cytosol and expression was strongly induced by
      plant cultivation on TNT-containing media. Oxidation of [C(3)H(3)]TNT by
      peroxidase and phenoloxidase was also studied. In contrast to the strongly
      induced nitroreductase, levels of these enzymes changed very little with TNT
      addition. This suggests that the main pathway of TNT transformation in plant
      cells is nitro group reduction. A plant's nitroreductase activity and its ability
      to incorporate TNT from aqueous solutions were correlated in four plants that
      were studied. The results suggest that plant nitroreductase activity may serve as
      a good biochemical indicator of plants that can be used for phytoremediation of
      soils contaminated with TNT.

PMID- 16002140
TI  - Morphometric studies of specific brain regions of rats chronically intoxicated
      with the organophosphate methamidophos.
AB  - Subtle neurological disturbances have been described in organophosphorus
      intoxication. Experimental studies have reported neuronal necrosis, particularly
      in animals experiencing seizures. The objective of the present work was to
      investigate if in rats (without seizures) exposed to an organophosphate agent,
      morphological changes occur in specific regions of the brain. The animals
      received 2.5 or 5.0 mg/kg methamidophos once a week for 2 months and were
      decapitated after 2 months 7 days of drug administration. We observed atrophy of
      the molecular layer of the parietal cortex without neuronal loss in specific
      cerebral regions. This would be due to atrophy or loss of neuronal ramifications
      but without neuronal loss.

PMID- 16002141
TI  - Tissue-dependent distribution and accumulation of chlorobenzenes by vegetables in
      urban area.
AB  - Five seasonal vegetables from three growing sites in Hangzhou city, Zhejiang
      Province, were studied for the levels of four chlorobenzenes(CBs): o
      dichlorobenzene (o-DCB), p-dichlorobenzene (p-DCB), m-dichlorobenzene (m-DCB),
      and 1,2,4-trichlorobenzene (1,2,4-TCB). Samples of each vegetable from each site
      were subdivided into leaves, stems, and roots, and these subsamples were analyzed
      separately for the levels of accumulated CBs. Relations between the levels of CBs
      in vegetables with the total organic carbon (TOC) of the soil, the lipid content
      of the vegetable, and the physicochemical properties of CBs were established.
      Results showed that o-DCB, p-DCB, m-DCB, 1,2,4-TCB were present in all vegetables
      analyzed. For spinaches (Spinacia oleracea), Chinese cabbages (Brassica rapa var.
      pekinensis), and celery (Apium graveolens var. dulce), the highest level of CBs
      was with roots, followed by leaves. While for radishes (Raphanus sativus), and
      carrots (Daucus carota subsp. sativus), the highest level was with leaves,
      followed by stems. The accumulation of CBs was found to have a good correlation
      with the plant-tissue lipid content, the contaminant air-water Henry's
      coefficient (H), the contaminant octanol-water partition coefficient (K(ow)), and
      the physiological characteristics of the vegetables.

PMID- 16002142
TI  - Identification of weed plants excluding the uptake of heavy metals.
AB  - Using the field pot-culture and sample-analysis method, 54 weed species belonging
      to 20 families and 31 weed species belonging to 17 families were systematically
      examined as to whether they can exclude the uptake of heavy metals. After a
      systematic identification, it was determined that Oenothera biennis and Commelina
      communis were Cd-excluders and Taraxacum mongolicum was a Zn-excluder. O. biennis
      is a potential Cd-excluder, but also a potential Cu-excluder. The research raises
      the possibility of making a major breakthrough in the application of metal
      excluders for safe agro-production in the future.

PMID- 16002143
TI  - Liver inflammation and regeneration: two distinct biological phenomena or
      parallel pathophysiologic processes?
AB  - The anatomic localization and unique vasculature of the liver, along with its
      cell properties, make this organ an efficient line of defense against blood-borne
      infections, either systemic or arising in the abdomen. Liver cells can modify the
      host immune response by releasing immunomodulatory molecules, interacting with
      cells of the immune system and acting as scavengers for inflammatory mediators.
      However, these defensive functions do not protect the liver itself from the
      severe injury that may be caused by pathogens, toxins or pollutant xenobiotics.
      Therefore, the mammalian liver has developed a unique adaptation in the form of
      an astonishing regenerative capability. The complexity of regeneration requires a
      well-orchestrated system to control this process. Growing evidence suggest the
      importance of immune mechanisms as a part of this system. It seems likely that
      the mechanisms that serve to eliminate infections (and may simultaneously cause
      liver injury) are also active in restoring the structural and functional
      integrity of the damaged liver.

PMID- 16002144
TI  - Review of a proposed mechanism for the antinociceptive action of botulinum toxin
      type A.
AB  - Botulinum toxin type A (BOTOX) has been used to treat pathological pain
      conditions although the mechanism is not entirely understood. Subcutaneous (s.c.)
      BOTOX also inhibits inflammatory pain in the rat formalin model, and the present
      study examined whether this could be due to a direct action on sensory neurons.
      BOTOX (3.5-30 U/kg) was injected s.c. into the subplantar surface of the rat hind
      paw followed 1-5 days later by 50 mL of 5% formalin. Using microdialysis, we
      found that BOTOX significantly inhibited formalin-induced glutamate release (peak
      inhibitions: 35%, 41%, and 45% with 3.5, 7, and 15 U/kg, respectively). BOTOX
      also dose dependently reduced the number of formalin-induced Fos-like
      immunoreactive cells in the dorsal horn of the spinal cord and significantly (15
      and 30 U/kg) inhibited the excitation of wide dynamic range neurons of the dorsal
      horn in Phase II but not Phase I of the formalin response. These results indicate
      that s.c. BOTOX inhibits neurotransmitter release from primary sensory neurons in
      the rat formalin model. Through this mechanism, BOTOX inhibits peripheral
      sensitization in these models, which leads to an indirect reduction in central
      sensitization.

PMID- 16002145
TI  - Crystal structure, solid state and solution characterisation of copper(II)
      coordination compounds of ethyl 5-methyl-4-imidazolecarboxylate (emizco).
AB  - The synthesis and characterisation of the following compounds derived from the
      biological relevant compound ethyl 5-methyl-4-imidazolecarboxylate (emizco) (1):
      [Cu(emizco)Cl2] (2), [Cu(emizco)2Cl2] (3), [Cu(emizco)2Br2] (4),
      [Cu(emizco)2(H2O)2](NO3)2 (5) and [Cu(emizco)4](NO3)2 (6), is presented. These
      compounds were characterised by IR and UV spectroscopic techniques, in addition
      the crystal structures of compounds 1-5 were determined. For complexes 2-5,
      emizco is coordinated as a bidentate ligand, through the oxygen atom of the
      carboxylate moiety and the nitrogen atom of the imidazolic ring. Different
      geometries are stabilised: compound 2 includes a pentacoordinated square
      pyramidal metal centre, while 3-5 are derived from octahedral geometry. Halide
      compounds 3 and 4 show a cis-octahedral arrangement, which is not very common on
      [CuN2O2X2] systems, while 5 stabilises the trans-octahedral isomer. Compound 6
      displays a square planar geometry. Finally, hydrolysis of emizco to its
      corresponding carboxylic acid (mizco), allowed the preparation of another square
      planar complex 7, identified as [Cu(mizco)2] 0.5H2O. Solution studies of these
      compounds indicate that emizco is not substituted from the coordination sphere,
      remaining as a bidentate ligand. Halides are substituted by water molecules,
      changing from cis octahedral to the trans-[Cu(emizco)2(H2O)2]2+ isomer.

PMID- 16002146
TI  - Bacteriophage-based assays for the rapid detection of rifampicin resistance in
      Mycobacterium tuberculosis: a meta-analysis.
AB  - OBJECTIVE: To summarize, using meta-analysis, the accuracy of bacteriophage-based
      assays for the detection of rifampicin resistance in Mycobacterium tuberculosis.
      METHODS: By searching multiple databases and sources we identified a total of 21
      studies eligible for meta-analysis. Of these, 14 studies used phage amplification
      assays (including eight studies on the commercial FASTPlaque-TB kits), and seven
      used luciferase reporter phage (LRP) assays. Sensitivity, specificity, and
      agreement between phage assay and reference standard (e.g. agar proportion method
      or BACTEC 460) results were the main outcomes of interest. RESULTS: When
      performed on culture isolates (N=19 studies), phage assays appear to have
      relatively high sensitivity and specificity. Eleven of 19 (58%) studies reported
      sensitivity and specificity estimates > or =95%, and 13 of 19 (68%) studies
      reported > or =95% agreement with reference standard results. Specificity
      estimates were slightly lower and more variable than sensitivity; 5 of 19 (26%)
      studies reported specificity <90%. Only two studies performed phage assays
      directly on sputum specimens; although one study reported sensitivity and
      specificity of 100 and 99%, respectively, another reported sensitivity of 86% and
      specificity of 73%. CONCLUSIONS: Current evidence is largely restricted to the
      use of phage assays for the detection of rifampicin resistance in culture
      isolates. When used on culture isolates, these assays appear to have high
      sensitivity, but variable and slightly lower specificity. In contrast, evidence
      is lacking on the accuracy of these assays when they are directly applied to
      sputum specimens. If phage-based assays can be directly used on clinical
      specimens and if they are shown to have high accuracy, they have the potential to
      improve the diagnosis of MDR-TB. However, before phage assays can be successfully
      used in routine practice, several concerns have to be addressed, including
      unexplained false positives in some studies, potential for contamination and
      indeterminate results.

PMID- 16002147
TI  - An elderly lady with sudden blindness and a sore foot.
AB  - We report the case of an elderly woman presenting with group G streptococcal
      septicaemia associated with osteomyelitis and endophthalmitis.

PMID- 16002148
TI  - Subthreshold depression is linked to the functional polymorphism of the 5HT
      transporter gene.
AB  - BACKGROUND: The functional polymorphism of the serotonin transporter gene
      (5HTTLPR) has been earlier associated with affective disorders. No research has
      however been carried out to identify the relationship between this polymorphism
      and depressive traits and subclinical depressive symptoms within a
      psychiatrically healthy population. METHODS: One hundred and twenty-eight female
      subjects with no lifetime or current history of DSM-IV Axis I disorders
      participated in the study. All subjects completed the Zung Self-Rating Depression
      Scale and were genotyped for the 5HTTLPR polymorphism. RESULTS: Significant
      differences were found on the Zung SDS and also on the physical-vegetative
      subscale of the Zung SDS according to both phenotype and genotype. Subjects
      carrying the s allele scored significantly higher on the Zung SDS and had also
      significantly higher scores on the physical-vegetative symptom subscale.
      Furthermore, subjects carrying the ss genotype scored highest and subjects
      carrying the ll genotype scored the lowest on both scales. CONCLUSION:
      Subclinical depressive symptoms (i.e. DSM-IV subthreshold depression) are
      associated with the functional polymorphism of the serotonin transporter gene.
      The main association between this polymorphism and subclinical depression is
      primarily carried by the physical symptoms of depression. The s allele of the
      5HTTLPR gene is associated with a "low mood endophenotype".

PMID- 16002149
TI  - Use of biodegradable PLGA microspheres as a slow release delivery system for the
      Boophilus microplus synthetic vaccine SBm7462.
AB  - The synthetic anti-Boophilus microplus vaccine SBm7462 derived from the tick
      intestinal protein, Bm86, induced a protective immune response when emulsified in
      saponin and used in cattle. Using a mice model, and with the objective of
      improving the vaccine by continual peptide release, it was encapsulated in PLGA
      50:50 microspheres and inoculated in BALB/c mice to assess the immunological
      response by detection of anti-peptide IgGs. Comparative studies were made with
      the peptide emulsified in saponin and with another synthetic vaccine, and the
      microsphere/peptide was characterized for efficiency of encapsulation, in vitro
      release profile, morphology, size, peptide integrity after encapsulation and
      stability in different pHs. The findings showed that saponin enhances a better
      immune response from SBm7462 and that the PLGA 50:50 microspheres are suitable
      for use with this peptide.

PMID- 16002150
TI  - Activation of purified allogeneic CD4(+) T cells by rat bone marrow-derived
      dendritic cells induces concurrent secretion of IFN-gamma, IL-4, and IL-10.
AB  - Dendritic cells (DCs) are highly specialized antigen-presenting cells that play a
      key role in the initiation and regulation of immune responses. The ability of DCs
      to process antigens and the outcome of their interaction with T cells are largely
      dependent on phenotype as well as maturation state of DCs. In this study, we
      generated DCs from rat bone marrow precursors. Bone marrow cells cultured in the
      presence of granulocyte macrophage colony-stimulating factor (GM-CSF),
      interleukin (IL)-4, and Flt-3 ligand (FL) produced immature DCs that expressed
      intermediate levels of major histocompatibility complex (MHC) class II, low
      levels of CD80 and CD86 molecules and displayed a high capacity of endocytosis.
      Bone marrow-derived DCs (BMDCs) matured in the presence of lipopolysaccharide
      (LPS) upregulated expression of MHC class II, CD80 and CD86, while their
      phagocytic capacity was dramatically reduced. Mature BMDCs stimulated vigorous
      proliferation of purified allogeneic CD4(+) T cells in a primary mixed leukocyte
      reaction (MLR) and elicited a mixed cytokine profile in allogeneic CD4(+) T
      cells: DCs activated CD4(+) T cells to produce interferon (IFN)-gamma, IL-4, and
      IL-10. Thus, rat BMDCs effectively internalize antigens and stimulate T cell
      proliferation but fail to induce an unidirectional polarization of T helper
      (T(H)) cells and in this respect differ from both human and mouse DCs.

PMID- 16002151
TI  - Eph/ephrin A- and B-family expression patterns in the leopard frog (Rana
      utricularia).
AB  - Eph/ephrin expression was studied in Rana utricularia larvae and adults with in
      situ receptor and ligand affinity probes. From stages TK-II (early limb bud) to
      VI (early foot paddle larva), tectal EphB expression is highest in a band
      extending transversely across the posterior optic tectum and grades off
      anteriorly and posteriorly. The ephrin-A expression gradient is parallel to the
      EphB gradient rather than being orthogonal to it. However, its high point
      occupies the posterior pole, and it runs from high-posteriorly to low-anteriorly.
      Tectal EphA expression is high anteriorly and low posteriorly, while ephrin-Bs
      are expressed only in a thin line at the dorsal midline. At later stages and in
      adults, tectal EphB expression becomes uniform.

PMID- 16002152
TI  - High dose methylprednisolone induces FcgammaRI on granulocytes in MS-patients.
AB  - Immune complexes impinge on receptors for the Fc domain of IgG (FcgammaR) and may
      thus influence the disease course in multiple sclerosis (MS). We analyzed
      FcgammaR distribution on monocytes and granulocytes in twenty relapsing-remitting
      MS patients at baseline, immediately after a five day course of high dose
      intravenous methylprednisolone (IVMP) treatment and after two months. After a
      five day course of IVMP the proportion of granulocytes with FcgammaRI was
      increased, P=0,002. There was no change in FcgammaRII and FcgammaRIII expression.
      The effect of IVMP on FcgammaRI expression could be important for the clearance
      of immune complexes in MS.

PMID- 16002153
TI  - Incidence of unexpected pathology in routine adenoidectomy specimens.
AB  - OBJECTIVE: The aim of this study was to determine the incidence of unexpected
      pathologies in adenoidectomy specimens and necessity for histopathologic
      evaluation of adenoid tissue. MATERIALS AND METHODS: All patients younger than 16
      years who underwent routine adenoidectomy were reviewed. Patients were excluded
      if the primary surgery was other than routine adenoidectomy such as
      nasopharyngeal biopsy for suspicion of malignancy or other pathology. RESULTS:
      One thousand one hundred eighty-four patients (683 males, 501 females) were
      involved in this study. The mean age was 7.53+/-3.24 years, ranging between 2 and
      16 years. There was no patient with unexpected pathology among 1184 routine and
      primary adenoidectomy procedures. However, one patient had unexpected pathology
      among 33 revision adenoidectomy procedures (3%). CONCLUSIONS: There was no occult
      pathology in routine primary adenoidectomy. The incidence of unexpected pathology
      in revision adenoidectomy was 3%. Microscopic evaluation of adenoid tissue gives
      some knowledge about histological properties and rarely some unexpected
      pathologies. Searching for malignancy is unnecessary in routine primary
      adenoidectomy cases without any other clinical, radiological and laboratory
      findings.

PMID- 16002154
TI  - The effect of local injection of botulinum toxin A on the immunoreactivity of
      nNOS in the rat submandibular gland: an immunohistochemical study.
AB  - PURPOSE: In our study, we intend to investigate the influence of local injections
      of botulinum toxin A on the activity of neuronal nitric oxide synthase (nNOS) in
      submandibular glands of adult rats. Since interest has been focused on the role
      of nitric oxide (NO) as a possible neuromodulator of secretory regulation
      processes in the upper aerodigestive tract, it was the aim of the present study
      to show that the toxin also interferes with the metabolic actions of NO on
      investigated rat submandibular glands. It is of great clinical interest whether
      the NO pathway is able to influence salivary gland secretion. Increasing of
      knowledge in this field maybe helpful to treat sialorrhoea, especially in
      juvenile otolaryngologic and neurologic patients. MATERIALS AND METHODS: We
      performed immunohistochemical reaction of neuronal nitric oxide synthase (nNOS)
      in the submandibular gland of female adult Wistar rats, both in native
      (untreated) glands and after intraglandular injection of botulinum toxin A under
      general anesthesia. The immunoreactivity of nNOS was investigated on different
      times after injection. RESULTS: Other than in the untreated glands, there was a
      significant decrease of nNOS in the treated organs, which became stronger with
      extended toxin exposure time. The present study shows explicit data on the effect
      of botulinum toxin A injection on a higher number of examined submandibular
      glands and is able to analyze a time course of the effect duration. CONCLUSION:
      In our study, it was shown that botulinum toxin A had an influence on the
      immunoreactivity of neuronal nitric oxide synthase (nNOS) in submandibular
      glands. Therefore, the participation of nitric oxide (NO) in the regulation of
      secretion from these organs seems to be evident. It might be assumed that the
      influence of botulinum toxin A on nNOS in the submandibular gland of the rat is
      able to explain the sometimes longer duration of toxin effect at the
      neuroglandular junction than at the motor endplate.

PMID- 16002155
TI  - Alternative methods for validation of cell culture infection with duck hepatitis
      B virus.
AB  - Hepatitis B virus (HBV) is an important virus used in disinfection procedures for
      blood spillage. However, validation of HBV inactivation is difficult, since there
      are no feasible infectivity assays. In some countries, the duck HBV (DHBV) is
      recognized as a suitable model for testing antiviral activity of chemical
      biocides against HBV. Currently, DHBV-infected ducks are required for preparation
      of the test virus as well as eggs from DHBV-free flocks for testing DHBV
      infectivity. To improve the practicality of the system, we suggested to use
      commercially available embryonated duck eggs for preparation of DHBV-susceptible
      hepatocyte cultures and to exclude infected hepatocytes by pre-screening with
      qualitative detection of DHBV DNA using polymerase chain reaction (PCR). A
      standardized DHBV test virus was prepared from the DHBV DNA-transfected hepatoma
      cell line D2, which contained 10(11)DHBV DNA molecules per mL detected by light
      cycler real-time PCR. Infection of cell cultures was most efficient 4 days after
      plating. The best identification of infected cultures was possible 6 days after
      infection with immunofluorescence using an antiserum against DHBV surface
      antigen.

PMID- 16002156
TI  - Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T
      (DAPTA).
AB  - The chemokine receptor CCR5 plays a crucial role in transmission of HIV isolates,
      which predominate in the early and middle stages of infection, as well as those,
      which populate the brain and cause neuro-AIDS. CCR5 is therefore an attractive
      therapeutic target for design of entry inhibitors. Specific rapid filtration
      binding assays have been useful for almost 30 years both for drug discovery and
      understanding molecular mechanisms of drug action. Reported in 1986, prior to
      discovery of chemokine co-receptors and so thought to act at CD4, peptide T
      (DAPTA) appears to greatly reduce cellular viral reservoirs in both HAART
      experienced and treatment naive patients, without toxicities. We here report that
      DAPTA potently inhibits specific CD4-dependent binding of gp120 Bal (IC50=0.06
      nM) and CM235 (IC50=0.32 nM) to CCR5. In co-immunoprecipitation studies, DAPTA (1
      nM) blocks formation of the gp120/sCD4 complex with CCR5. Confocal microscopic
      studies of direct FITC-DAPTA binding to CCR5+, but not CCR5-, cells show that
      CCR5 is a DAPTA receptor. The capability of DAPTA to potently block gp120-CD4
      binding to the major co-receptor CCR5 explains its molecular and therapeutic
      mechanism of action as a selective antiviral entry inhibitor for R5 tropic HIV-1
      isolates.

PMID- 16002157
TI  - Prognostic value of interleukin-8 as a predictor of heart failure in patients
      with myocardial infarction and percutaneous intervention.
AB  - BACKGROUND: Recent studies have shown that pro-inflammatory cytokines play a
      significant contributory role in the pathogenesis of the acute heart failure. The
      purpose of this study was to determine whether the serum IL-8 concentration in
      patients with acute myocardial infarction (AMI), who were undergoing percutaneous
      coronary intervention (PCI) was related to the subsequent presence or absence of
      heart failure. METHODS: The study included 50 patients who underwent successful
      PCI. During their subsequent stay in the coronary care unit, their maximum degree
      of heart failure was recorded. Patients were then divided into two groups: group
      A (Killip I) and group B (Killip class > I). The serum IL-8 concentration was
      measured during the 24 h following admission to the coronary care unit. RESULTS:
      Serum levels of IL-8 in the group B were significantly higher than those of group
      A (P < 0.001). By multivariante analysis a higher level of IL-8 was a significant
      predictor of heart failure after PCI. CONCLUSIONS: Serum levels of IL-8 after PCI
      appear to be a predictor for the development of heart failure in patients with
      AMI.

PMID- 16002159
TI  - Anomalous "benign" coronary arteries detected by multidetector computed
      tomography.
AB  - Being usually asymptomatic, anomalous coronary arteries (ACAs) are discovered in
      adulthood using invasive coronary angiography (CA) performed for suspected
      coronary artery disease. However, if only based on CA, the correct diagnosis is
      not easily made. We report on the importance of integrated data obtained by using
      multidetector computed tomography, and perfusional myocardial scintigraphy as
      alternative non-invasive imaging techniques in evaluating the exact course and
      the functional importance of usually considered "benign" ACAs in three
      symptomatic subjects, and of the development of official recommendations for the
      practitioners in the management of such patients.

PMID- 16002158
TI  - Inaccuracy of dipyridamole echocardiography or scintigraphy for the diagnosis of
      coronary artery disease in patients with both left bundle branch block and left
      ventricular dysfunction.
AB  - Non-invasive diagnosis of coronary artery disease (CAD) in patients with left
      ventricular (LV) dysfunction and left bundle branch block (LBBB) remains
      challenging, and there is no consensus on the role of myocardial sesta-MIBI
      perfusion scintigraphy with pharmacological stress (dip-MIBI) or dipiridamole
      echocardiography (dip-ECHO). We thus performed a prospective study to test the
      diagnostic accuracy of such non-invasive tests. 27 consecutive patients with both
      LV dysfunction and LBBB undergoing diagnostic work-up for CAD were studied
      simultaneously with dip-ECHO and dip-MIBI. The sensitivity for CAD for dip-ECHO
      and dip-MIBI was respectively 42% and 67%, with specificity 93% and 53%, and
      likelihood ratio (LR)-positive 6.3 and LR-negative 0.6 for both. Given the low
      accuracy of both dip-ECHO and dip-MIBI in detecting CAD in patients with
      concomitant LV dysfunction and LBBB, coronary angiography should be performed as
      the default diagnostic strategy in such patients.

PMID- 16002160
TI  - The impact of early administration of low-dose atorvastatin treatment on
      inflammatory process, in patients with unstable angina and low cholesterol level.
AB  - BACKGROUND: Lipid-lowering agents are known to reduce long-term mortality in
      patients with stable angina or multiple risk factors. However, the effects of
      lipid-lowering treatment on inflammatory process during and immediately after the
      acute phase of unstable angina remain unclear. In this study we assessed the
      effects of low-dose atorvastatin treatment, on inflammatory process in patients
      admitted for unstable angina with low cholesterol level. METHODS: Forty-seven
      normocholesterolemic patients with unstable angina were randomized into two
      groups, and received atorvastatin 10 mg/day (n = 24) or no statin (n = 23) for 6
      weeks. Circulating levels of inteleukin 6 (IL-6), monocyte chemoattractant
      protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and soluble vascular
      cell adhesion molecule (sVCAM-1) were measured by their admission, and at the 1st
      and 6th week of the study. RESULTS: Serum levels of MCP-1 and sVCAM-1 were
      significantly increased in the control group (p < 0.05) while remained unaffected
      in the atorvastatin-treated group six weeks after admission. However, IL-6 and
      TNF-alpha levels were similarly decreased in both atorvastatin-treated and
      control groups. CONCLUSION: Low-dose atorvastatin treatment modifies inflammatory
      process in patients with unstable angina and low cholesterol level, an effect
      seen at 6 weeks but not 1 week after admission.

PMID- 16002161
TI  - Effects of long-term oral treatment with selective vasopressin V2 receptor
      antagonist (OPC-31260) on adriamycin-induced heart failure in rats.
AB  - BACKGROUND: In the treatment of heart failure, the effects of therapeutic agents
      on life prognosis remains unclear. We investigated the effects of long-term oral
      administration of a nonpeptide, selective, vasopressin V2 receptor antagonist,
      OPC-31260, on Sprague-Dawley rats that were treated with adriamycin to induce
      progressive water retention. METHODS: Intraperitoneal saline was administered to
      14 rats as a control (Group 1). A total cumulative dose of 15 mg/kg of adriamycin
      was administered intraperitoneally in six equal doses over a period of 2 weeks to
      another 52 rats. Adriamycin-treated rats were further divided into Group 2, which
      received saline (p.o.), and Group 3, which received 50 mg/kg (p.o.) of V2
      antagonist. Oral administration continued every day for 6 weeks. Group 1 rats
      also received saline (p.o.) for 6 weeks. RESULTS: The V2 antagonist decreased
      urine osmolality and increased diuresis of rats in Group 3. Urinary excretion of
      electrolytes was not increased by the V2 antagonist in Group 3. Serum osmolality
      was likewise unchanged by the V2 antagonist in Group 3. Plasma concentrations of
      vasopressin were significantly higher in Group 3 than in the other groups (Group
      1, 4.0+/-1.1 pg/ml; Group 2, 4.2+/-1.5 pg/ml; Group 3, 8.5+/-1.0 pg/ml; p<0.05).
      During the experimental period, survival rate was higher in Group 3 than in Group
      2 (Group 1, 100%; Group 2, 59%; Group 3, 83%). CONCLUSION: Our data show that
      administration of orally active V2 antagonist did not reduce the survival of
      adriamycin-treated rats through continuous aquaretic action, despite elevated
      plasma levels of vasopressin.

PMID- 16002162
TI  - Anomalous origin of right coronary artery: magnetic resonance angiography and
      viability study.
AB  - OBJECTIVE: To detect origin and course and to evaluate viability in patients with
      anomalous RCA. DESIGN: 3D coronary MR angiography and viability study using
      gadolinium-enhanced magnetic resonance imaging (Gd-MRI) was performed. SETTING: A
      tertiary hospital center. PATIENTS: Four patients, selected from the catheter
      lab, were studied. RESULTS: Anomalous RCA from the left sinus of Valsalva was
      identified in all patients. Inferior myocardial infarction was documented in
      three patients. CONCLUSIONS: Magnetic resonance imaging can non-invasively
      identify anomalous RCA and perform viability study in the same examination.

PMID- 16002163
TI  - Prediction of depressive disorder following myocardial infarction data from the
      Myocardial INfarction and Depression-Intervention Trial (MIND-IT).
AB  - BACKGROUND: Depression following myocardial infarction (MI) is associated with
      complicated cardiac rehabilitation, non-compliance and poor prognosis. Whether
      depression following MI can be predicted from variables routinely assessed during
      hospitalization for MI is unknown. METHODS: Using data from the Myocardial
      INfarction and Depression-Intervention Trial (MIND-IT), we identified 2,177 MI
      patients (mean age 63 years; 23% female). Patients were randomly divided into a
      derivation and a validation sample. In the derivation sample, we analyzed
      variables potentially associated with the development of post-MI depressive
      disorder, which were tested in the validation sample. RESULTS: In the year
      following MI, 18.5% suffered from depressive disorder (ICD-10 criteria). In a
      multivariate model, factors associated with depression were younger age (OR 1.94;
      CI 1.38-2.74), hypercholesterolemia (OR 1.68; CI 1.08-2.61), the use of calcium
      channel blockers at discharge (OR 1.80; CI 1.20-2.71), and left ventricular
      ejection fraction (LVEF) (OR 4.14 for patients with LVEF <30%; CI (2.42-7.10).
      The derived predictors were tested in the validation sample. The final model
      yielded two clinical predictors, i.e., younger age and severe LV-dysfunction,
      which correctly predicted post-discharge depression status in 82.9% of the MI
      patients. The model yielded a high negative predictive value (89%). A positive
      depression questionnaire (BDI) during hospitalization increased the positive
      predictive value of 23% to 52%. CONCLUSIONS: During hospitalization for MI and
      using a two-step strategy with common clinical variables, i.e., younger age,
      severe LV-dysfunction and BDI score during hospitalization, it is possible to
      identify MI patients with a high risk for subsequent development of depression.

PMID- 16002164
TI  - Increased plasma soluble adhesion molecules; ICAM-1, VCAM-1, and E-selectin
      levels in patients with slow coronary flow.
AB  - BACKGROUND: Inflammation has been reported to be a major contributing factor to
      many cardiovascular events. In the present study, we aimed to evaluate plasma
      soluble adhesion molecules; intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1) and E-selectin as possible indicators of
      endothelial activation or inflammation in patients with slow coronary flow.
      METHOD: Study population included 17 patients with angiographically proven normal
      coronary arteries and slow coronary flow in all three coronary vessels (group I,
      11 male, 6 female, mean age=48+/-9 years), and 20 subjects with angiographically
      proven normal coronary arteries without associated slow coronary flow (group II,
      11 male, 9 female, mean age=50+/-8 years). Coronary flow rates of all patients
      and control subjects were documented by Thrombolysis In Myocardial Infarction
      frame count (TIMI frame count). All patients in group I had TIMI frame counts
      greater than two standard deviation above those of control subjects (group II)
      and, therefore, were accepted as exhibiting slow coronary flow. Serum levels of
      ICAM-1, VCAM-1, and E-selectin were measured in all patients and control subjects
      using commercially available ELISA kits. RESULTS: Serum ICAM-1, VCAM-1, and E
      selectin levels of patients with slow coronary flow were found to be
      significantly higher than those of control subjects with normal coronary flow
      (ICAM-1: 545+/-198 ng/ml vs. 242+/-113 ng/ml respectively, p<0.001, VCAM-1:
      2040+/-634 ng/ml vs. 918+/-336 ng/ml respectively, p<0.001, E-selectin: 67+/-9
      ng/ml vs. 52+/-8 ng/ml respectively, p<0.001). Average TIMI frame count was
      detected to be significantly correlated with plasma soluble ICAM-1 (r=0.550,
      p<0.001), VCAM-1 (r=0.569, p<0.001) and E-selectin (r=0.443, p=0.006).
      CONCLUSION: Increased levels of soluble adhesion molecules in patients with slow
      coronary flow may be an indicator of endothelial activation and inflammation and
      are likely to be in the causal pathway leading to slow coronary flow.

PMID- 16002165
TI  - Takayasu arteritis: role of cardiovascular magnetic imaging.
AB  - Takayasu arteritis (TA) is a primary arteritis of unknown cause that commonly
      affects the aorta and its main branches. Traditionally, X-ray contrast
      angiography has been the gold standard for diagnosis and review of this chronic
      disease but recent developments suggest that non-invasive imaging with
      multiplanar cardiovascular magnetic resonance imaging (CMR) and magnetic
      resonance angiography (MRA) have a number of advantages for use in routine care.
      This review utilises a series of cases referred for imaging at the Royal Brompton
      Hospital, London to illustrate these points of development.

PMID- 16002166
TI  - The prevalence of interatrial septal openings in newborns and predictive factors
      for spontaneous closure.
AB  - BACKGROUND: We aimed to establish the prevalence of interatrial septal openings
      (IASOs) in newborns, to define their natural course during the first year of
      life, and to find the predictor factors for their spontaneous closure. METHODS:
      One thousand and seventy two newborns were examined with echocardiography in
      early postnatal period. The length of interatrial septum (IASL) and IASO diameter
      were measured, and the "IASO/IASL" ratio was calculated for each case. According
      to the IASO diameter, study population was divided into 4 groups as Group 1 (< 3
      mm), Group 2 (> or = 3-5 mm), Group 3 (> or = 5-7 mm) and Group 4 (> or = 7 mm).
      RESULTS: The overall prevalence of IASOs was 78.6% (83.3% in preterms (105 of
      126) and 78.1% in full-terms (738 of 946)). The mean diameter of IASOs was 3.1+/
      1.1 mm. The overall spontaneous closure rate of IASOs at the end of the first
      year of life was 96.1% (99.3% in Group 1, 94.8% in Group 2, 64.8% in Group 3 and
      50.0% in Group 4). The spontaneous closure was earlier in Group 1 compared to
      other groups (p=0.011). There were positive correlations between the closure time
      and the diameter of IASOs, and closure time and "IASO/IASL" (p<0.001 and p<0.001
      respectively). The most important factors affecting the spontaneous closure time
      were the initial diameter of IASO and the "IASO/IASL" ratio (p<0.001 and p=0.029
      respectively). When the "IASO/IASL" ratio is < or = 33.3%, its sensitivity and
      specificity in predicting the spontaneous closure at the end of the first year
      were 99.1% and 88.2% respectively. CONCLUSIONS: The prevalence of IASOs in
      newborns and spontaneous closure rate of the IASOs with a diameter of less than 5
      mm are very high. In addition to the initial diameter of IASO, the "IASO/IASL"
      ratio is also an important predictor for spontaneous closure.

PMID- 16002167
TI  - Optimisation of intact cell MALDI method for fingerprinting of methicillin
      resistant Staphylococcus aureus.
AB  - The use of matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF)
      mass spectrometry on intact cell microorganisms, Intact Cell MALDI (ICM), has
      been shown by numerous workers to yield effective species level identification.
      Early work highlighted the significant effect that variation in culture media,
      incubation conditions and length of incubation had on the spectra produced.
      Therefore, in order to achieve reliable and reproducible species level
      identification and sub-typing of microorganisms from ICM fingerprints, it has
      been essential to develop standardised methods. For methicillin-resistant
      Staphylococcus aureus (MRSA), a major nosocomial pathogen, we have developed such
      a standardised method. In this paper we present the experimental parameters,
      namely, the incubation period, the number of passages required from lyophilised
      or stored isolates, the method of deposition of the bacterial cells, the
      concentration of matrix solution, the drying time of bacterial cells prior to the
      addition of the matrix solution, the time between preparation of the
      bacterial/matrix sample and analysis and the MALDI pulsed extraction setting,
      which were considered during the development of defined methods.

PMID- 16002168
TI  - Long-term stability of frontal electroencephalographic asymmetry in adults with a
      history of depression and controls.
AB  - We investigated the stability in resting EEG across a 1- to 3-year interval in 49
      adults (33 female and 16 male) with a history of unipolar depression (first onset
      prior to the age of 14) and 50 controls (33 female and 17 male) with no history
      of major psychopathology. Current depressive symptoms were quantified by self
      report at both assessments. For the entire sample, EEG asymmetry in the alpha
      range was moderately stable (intraclass correlations between 0.39 and 0.61). Sex,
      history of depression, depressive symptom severity at Time 2, and change in
      symptom severity between Time 1 and Time 2 were unrelated to stability of EEG
      asymmetry. These findings support the view that resting frontal EEG asymmetry
      reflects a moderately stable individual difference in adults, irrespective of sex
      and history of depression.

PMID- 16002169
TI  - Effect of boiling and roasting on the fermentation of soybeans into dawadawa (soy
      dawadawa).
AB  - Soybeans which had initially been dehulled by either boiling (boiled/dehulled) or
      roasting (roasted/dehulled) before peeling, were cooked and fermented into
      dawadawa, a traditional food condiment. The micropopulation, enzymatic
      activities, proximate composition, amino acid, and aroma profiles of the two
      types of soybean dawadawa were evaluated during fermentation. Only minor
      differences were found in the microbial profiles of the two types of soy
      dawadawa. Although boiled/dehulled soy-dawadawa initially had lower microbial
      counts, it recorded higher counts at the advanced stages of fermentation.
      Proteolytic and amylolytic Bacillus species including Bacillus subtilis, Bacillus
      pumilus, Bacillus licheniformis, Bacillus cereus, and Bacillus firmus dominated
      the micropopulation of the two types of soy-dawadawa with Bacillus subtilis
      accounting for about 50% of the Bacillus species in all samples. Lactic acid
      bacteria and yeasts occurred in low numbers in the two types of soy-dawadawa. The
      proximate composition of the two types of soy-dawadawa were similar, and their
      contents of moisture and protein increased whilst fat and ash decreased during
      fermentation. Both types of fermenting soy-dawadawa recorded similar levels of
      alpha-amylase activity, but boiled/dehulled soy-dawadawa showed slightly higher
      protease activity. The levels of isoleucine, leucine, lysine, phenylalanine,
      arginine and proline increased significantly with fermentation time in both types
      of soy-dawadawa. With respect to differences in their aroma profiles,
      hexanodecanol, octadecyl acetate, 1,2-dimethyl benzene, tetradecene, (E)-5
      eicosene, cyclohexadecane, and hexacosane were found only in the roasted/dehulled
      samples, whilst 1,2-ethanediol, ethyl acetate, dimethyl disulfide,
      cyclotetradecane, decene, indole , 2 butyl-octenal, acetophenone, and toluene
      were found only in the boiled/dehulled samples. A market focus group showed
      preference for roasted/dehulled soy-dawadawa over boiled/dehulled soy-dawadawa.
      Apart from the volatile aroma compounds, the biochemical and microbiological
      profiles of the two types of soy-dawadawa showed only minor differences and were
      also similar to the profiles reported for African locust bean dawadawa.

PMID- 16002170
TI  - Protein response of insect cells to bioreactor environmental stresses.
AB  - Protein expression of Spodoptera frugiperda (Sf9) insect cells was characterized
      upon exposure to environmental stresses typically present in bioreactors
      including heat shock, oxygen deprivation, shear stress, change of pH, and
      salinity or ethanol shock. This study fills the void in knowledge as to how
      bioreactor hydrodynamics, anoxia, small changes in pH as well as salinity
      alterations due to pH control or exposure to ethanol used in asepsis treatments
      affect protein expression in Sf9 cells. Heat shock at 43 degrees C induced
      proteins at 83 kDa, 68-78 kDa and six small heat shock proteins (hsps) at 23-15.5
      kDa. Anaerobic conditions in CO2 atmosphere reduced significantly the normal
      protein synthesis and induced a small subset of heat shock proteins at 70 kDa.
      Oxygen deprivation in nitrogen atmosphere transiently induces the 70 kDa proteins
      and had minor effects on the normal protein synthesis. Exposure to increased
      salinity or ethanol concentration failed to trigger the stress response, but may
      extensively inhibit the induction of normal proteins even though there was a
      negligible change in cell viability. Shear stress that had a major reducing
      effect on cell viability did not change the protein synthesis profile of Sf9
      cells. Both long and short term exposures to small pH changes had negligible
      effects on protein synthesis.

PMID- 16002171
TI  - A murine model of dual infection with cytomegalovirus and Pneumocystis carinii:
      effects of virus-induced immunomodulation on disease progression.
AB  - Despite the use of antimicrobial prophylaxis, cytomegalovirus (CMV) and
      Pneumocystis carinii (PC) pneumonia (PCP) are both leading causes of morbidity
      and mortality in immunocompromised patients. It has previously been reported that
      CMV infection modulates host immune responses with a variety of mechanisms which
      include the suppression of helper T cell functions and antigen presenting cell
      (APC) functions, both of which are critical for PCP resolution. However, the
      mechanisms of these interactions and other possible immune regulatory effects are
      not clearly understood. In this study, we investigated the impact of murine CMV
      (MCMV) induced immunomodulation on the progression of PCP in a co-infection
      model. Initial results show that dually infected mice had evidence of more severe
      PC disease, which include a greater loss of body weight, an excess lung PC burden
      and delayed clearance of PC from lungs, compared to mice with PC infection alone.
      At day 7 post-infection, dually infected mice had reduced numbers of MHC-II
      expressing cells in the lung interstitium and lymph nodes and reduced migration
      of CD11c+ cells to both the tracheobronchial lymph nodes and alveolar spaces.
      Dual infected mice showed elevated numbers of specific CD8 responses concomitant
      with a decrease in activated CD4+ T cells in both the lymph nodes and in alveolar
      spaces when compared to mice infected with MCMV alone. These data suggest that
      MCMV infection inhibits the immune responses generated against PC which
      contribute to the delayed clearance of the organism.

PMID- 16002172
TI  - Regions of interest in FTIR imaging applications: diffusion of nicotine into
      ethylene-co-vinyl acetate films.
AB  - Effective image analysis of dynamic processes, such as diffusion and dissolution,
      requires precise reporting of component locations in space and time. An improved
      method for analyzing FTIR images is described which employs hypothesis testing in
      the spatial and temporal domains. Changes in the observed absorbance (over space
      and time) are revealed by comparison to a reference statistic, which can be
      tailored by choosing the size of a region of interest. This improved analysis
      method was used to compare the rates of diffusion of nicotine into poly(ethylene
      co-vinyl acetate) film from aqueous solutions containing anionic and nonionic
      surfactants. Compared to a solution without surfactant, sodium dodecyl sulfate
      inhibited the uptake of nicotine from aqueous solution whereas Tween 40 enhanced
      the uptake. The nicotine diffusion rate also showed a dependence on the length of
      the hydrophobic segment of nonionic surfactants. These results demonstrate the
      roles of solubilization, wetting, and viscosity on diffusion-controlled drug
      release.

PMID- 16002173
TI  - Oligonucleotide-protamine-albumin nanoparticles: Protamine sulfate causes drastic
      size reduction.
AB  - Nanoparticles prepared by self-assembly from oligonucleotides (ONs), protamine
      free base, and human serum albumin ("ternary proticles") are spheres of diameters
      around 200 nm. Substitution of the protamine free base by protamine sulfate leads
      to proticles of only around 40 nm in diameter with otherwise unchanged
      properties. The availability of drug delivery systems of very similar composition
      but grossly different size may be advantageous when dealing with cells which show
      size-dependent particle uptake. These nanoparticles are promising candidates for
      ON delivery to cells because of the following reasons: (1) They are stable for
      several hours in solutions of up to physiological ionic strength; (2) they are
      efficiently taken up by cells; (3) after cellular uptake, they easily release the
      ONs even when these are present as phosphorothioates.

PMID- 16002174
TI  - Jet-induced skin puncture and its impact on needle-free jet injections:
      experimental studies and a predictive model.
AB  - Needle-free jet injections constitute an important method of drug delivery,
      especially for insulin and vaccines. This report addresses the mechanisms of
      interactions of liquid jets with skin. Liquid jets first puncture the skin to
      form a hole through which the fluid is deposited into skin. Experimental studies
      showed that the depth of the hole significantly affects drug delivery by jet
      injections. At a constant jet exit velocity and nozzle diameter, the hole depth
      increased with increasing jet volume up to an asymptotic value and decreased with
      increasing values of skin's uniaxial Young's modulus. A theoretical model was
      developed to predict the hole depth as a function of jet and skin properties. A
      simplified model was first verified with polyacrylamide gels, a soft material in
      which the fluid mechanics during hole formation is well understood. Prediction of
      the hole depth in the skin is a first step in quantitatively predicting drug
      delivery by jet injection.

PMID- 16002176
TI  - C-reactive protein is elevated in obese patients with the metabolic syndrome.
AB  - C-reactive protein (CRP) is associated with increased risk for cardiovascular
      disease and diabetes. Few studies have evaluated the importance of CRP in those
      with the cluster of cardiovascular risk factors known as the metabolic syndrome
      (MS). We studied 190 overweight subjects (83 men and 107 women), aged 25-75
      years, screened for glucose intolerance, in order to assess whether CRP levels
      vary according to the presence of MS, and to examine the relationship between CRP
      levels and metabolic variables. The prevalence of the Adult Treatment Panel III
      MS was 36.8%. Subjects with the MS had a higher degree of insulin resistance
      (IR), measured by the homeostasis model assessment (HOMA) method (5.4+/-0.4
      versus 3.6+/-0.3, p<0.001) and higher frequency of glucose intolerance (78.3%
      versus 44.4%, p<0.001) than those without the MS. CRP values were increased among
      those with the MS (4.85+/-0.47 mg/l versus 3.34+/-0.36 mg/l, p<0.05). CRP
      correlated with waist circumference (r=0.28, p<0.001) and body mass index
      (r=0.38, p<0.001) in both men and women; however the relationship of CRP with
      HOMA(IR) was only evident in men (r=0.37, p<0.01) while the association with free
      fatty acids (FFA) was only significant in women (r=0.20, p<0.05), even after
      adjusting for age, hispanic ethnicity and glucose tolerance status. Abdominal
      obesity (elevated waist circumference) was the single most important MS component
      associated with increased CRP levels (>3mg/dl) (OR=3.1, 95% C.I.: 1.4-10.1),
      followed by female gender and smoking. These results confirm that CRP levels are
      elevated in MS subjects at risk for glucose intolerance. In addition waist
      circumference, HOMA(IR) and FFA levels are associated with CRP levels, suggesting
      potential roles of obesity, insulin resistance and lipolysis in the development
      of the subclinical inflammation associated with the MS.

PMID- 16002175
TI  - Safety and tolerability of pioglitazone, metformin, and gliclazide in the
      treatment of type 2 diabetes.
AB  - This analysis compares the safety and tolerability of pioglitazone (a
      thiazolidinedione), metformin (a biguanide), and gliclazide (a sulfonylurea).
      Data collected from four 1-year, double-blind studies comparing treatment of over
      3700 patients with type 2 diabetes with pioglitazone, metformin, or gliclazide
      have been combined to provide comparative tolerability and safety profiles. All
      treatments were well tolerated with approximately 6% of patients withdrawing from
      treatment because of side-effects. The side-effects profile varied between
      treatments, with pioglitazone being associated with edema, metformin with
      gastrointestinal side-effects, and gliclazide with hypoglycemia. Cardiovascular
      outcome was similar with all treatments, with no excess reports of cardiac
      failure with pioglitazone treatment. Both pioglitazone and gliclazide resulted in
      mean weight gain, whilst with metformin there was mean weight loss. Mean liver
      enzyme values decreased with pioglitazone and to a lesser extent with metformin.
      With gliclazide, mean liver enzyme values increased. The expected small decreases
      in mean hemoglobin and hematocrit seen with pioglitazone also occurred with
      metformin and to a lesser degree with gliclazide. The results show that all three
      drugs are safe, but that tolerability profiles vary. Each treatment provides an
      alternative therapy for type 2 diabetes, dependent on the particular needs of
      individual patients.

PMID- 16002177
TI  - Hospital management of animal and human bites.
AB  - The management of bites severe enough to warrant hospital admission is complex.
      This review includes the epidemiology, clinical management, investigations,
      microbiology and role of antimicrobials for all types of animal and human bites
      likely to be encountered in UK hospitals.

PMID- 16002178
TI  - Point-of-care controls for nosocomial legionellosis combined with chlorine
      dioxide potable water decontamination: a two-year survey at a Welsh teaching
      hospital.
AB  - This study reports a two-year programme of attempted eradication of Legionella
      colonization in the potable water supply of a 1000-bed tertiary care teaching
      hospital in Wales. There was a simultaneous, point-of-care, sterile-water-only
      policy for all intensive care units (ICU) and bone marrow and renal transplant
      units in order to prevent acquisition of nosocomial Legionnaires' disease. The
      programme was initiated following a case of nosocomial pneumonia caused by
      Legionella pneumophila serogroup 1-Bellingham-like genotype A on the cardiac ICU.
      The case occurred 14 days after mitral and aortic valve replacement surgery.
      Clinical and epidemiological investigations implicated aspiration of hospital
      potable water as the mechanism of infection. Despite interventions with chlorine
      dioxide costing over 25000 UK pounds per annum, Legionella has remained
      persistently present in significant numbers (up to 20000 colony forming units/L)
      and with little reduction in the number of positive sites. Two further cases of
      nosocomial disease occurred over the following two-year period; in one case,
      aspiration of tap water was implicated again, and in the other case, instillation
      of contaminated water into the right main bronchus via a misplaced nasogastric
      tube was implicated. These cases arose because of inadvertent non-compliance with
      the sterile-water-only policy in high-risk locations. Enhanced clinical
      surveillance over the same two-year period detected no other cases of nosocomial
      disease. This study suggests that attempts at eradication of Legionella spp. from
      complex water systems may not be a cost-effective measure for prevention of
      nosocomial infections, and to the best of our knowledge is the first study from
      the UK to suggest that the introduction of a sterile-water-only policy for ICUs
      and other high-risk units may be a more cost-effective approach.

PMID- 16002179
TI  - Surgical smoke and infection control.
AB  - Gaseous byproducts produced during electrocautery, laser surgery or the use of
      ultrasonic scalpels are usually referred to as 'surgical smoke'. This smoke,
      produced with or without a heating process, contains bio-aerosols with viable and
      non-viable cellular material that subsequently poses a risk of infection (human
      immunodeficiency virus, hepatitis B virus, human papillomavirus) and causes
      irritation to the lungs leading to acute and chronic inflammatory changes.
      Furthermore, cytotoxic, genotoxic and mutagenic effects have been demonstrated.
      The American Occupational Safety and Health Administration have estimated that
      500000 workers are exposed to laser and electrosurgical smoke each year. The use
      of standard surgical masks alone does not provide adequate protection from
      surgical smoke. While higher quality filter masks and/or double masking may
      increase the filtration capability, a smoke evacuation device or filter placed
      near (2-5 cm) the electrocautery blade or on endoscope valves offers additional
      (and necessary) safety for operating personnel and patients.

PMID- 16002180
TI  - An investigation of the factors that affect surgical hand disinfection with
      polyvidone iodine.
AB  - This study investigated the factors influencing the effectiveness of 7.5%
      polyvidone iodine as a surgical antiseptic. The study involved 100 operating
      staff (75 doctors and 25 nurses) from hospital surgical teams. Fingertips of both
      hands of the subjects were pressed on to agar culture before and after washing
      and after completion of surgery. Handwashing lasting for more than 3 min led to a
      significant decrease in the number of colonies compared with handwashing lasting
      for less than 3 min. Moreover, the number of colonies was significantly higher
      when surgery lasted for longer than 95 min. However, the handwashing style (with
      or without brushing) was not found to have a significant effect on the outcome of
      the disinfection procedure in terms of bacterial colonization. Subjects who had
      colonization of their hands after surgery were found to have significantly higher
      colony counts before handwashing compared with those who did not have any
      colonization on their hands after surgery. The results of this study revealed
      that in order to attain effective disinfection with polyvidone iodine, the
      duration of handwashing should be at least 3 min. The risk of recolonization
      increases when the duration of surgery exceeds 95 min.

PMID- 16002181
TI  - Reduction of exit-site infections of tunnelled intravascular catheters among
      neutropenic patients by sustained-release chlorhexidine dressings: results from a
      prospective randomized controlled trial.
AB  - Exit-site and tunnel infections of tunnelled central intravascular catheters are
      a frequent source of morbidity among neutropenic patients and may necessitate
      catheter removal. They require antimicrobial therapy that increases healthcare
      costs and is associated with adverse drug reactions. A prospective randomized
      clinical trial was conducted among adult patients undergoing chemotherapy in a
      haematology unit. Tunnelled intravascular catheters were randomized to receive
      the control of a standard dressing regimen as recommended by the British
      Committee for Standards in Haematology, or to receive the intervention of a
      sustained-release chlorhexidine dressing. Follow-up data were available in 112 of
      114 tunnelled intravascular catheters which were randomized. Exit-site or
      combined exit-site/tunnel infections occurred in 23 (43%) of 54 catheters in the
      control group, and five (9%) of 58 catheters in the intervention group [odds
      ratio (OR) for intervention group compared with control group =0.13, 95%
      confidence intervals (CI) 0.04-0.37, P<0.001]. More tunnelled intravascular
      catheters were prematurely removed from the control group than the intervention
      group for documented infections [20/54 (37%) vs 6/58 (10%), OR=0.20, 95%CI 0.53
      0.07]. However, there was no difference in the numbers of tunnelled intravascular
      catheters removed for all proven and suspected intravascular catheter-related
      infections [21/54 (39%) vs 19/58 (33%)], or in the time to removal of catheters
      for any reason other than death or end of treatment for underlying disease. Thus
      chlorhexidine dressings reduced the incidence of exit-site/tunnel infections of
      indwelling tunnelled intravascular catheters without prolonging catheter survival
      in neutropenic patients, and could be considered as part of the routine
      management of indwelling tunnelled intravascular catheters among neutropenic
      patients.

PMID- 16002182
TI  - Potential micro-organism transmission from the re-use of 3M Red Dot adhesive
      electrocardiograph electrodes.

PMID- 16002183
TI  - Antimicrobial susceptibility of polymerase chain reaction ribotypes of
      Clostridium difficile commonly isolated from symptomatic hospital patients in the
      UK.
AB  - Two hundred and seventy-one clinical isolates of Clostridium difficile, including
      the six most common polymerase chain reaction (PCR) ribotypes isolated from
      symptomatic patients in UK hospitals, were tested against nine antibiotics
      (imipenem, erythromycin, levofloxacin, piperacillin/tazobactam, ciprofloxacin, co
      amoxiclav, cefotaxime, amoxicillin and clindamycin). All 271 strains were
      susceptible to co-amoxiclav, piperacillin/tazobactam and amoxicillin, and
      resistant to cefotaxime and ciprofloxacin. Variable degrees of resistance were
      found to imipenem, erythromycin, levofloxacin and clindamycin. Significantly
      greater resistance to erythromycin, levofloxacin and imipenem was found in
      virtually all members of the two most common PCR ribotypes, 001 and 106.
      Resistance to these agents may have played a part in their selection as the most
      common strains of C. difficile found in UK hospitals.

PMID- 16002184
TI  - A modified pulsed-field gel electrophoresis (PFGE) protocol for subtyping
      previously non-PFGE typeable isolates of Clostridium difficile polymerase chain
      reaction ribotype 001.
AB  - A modified pulsed-field gel electrophoresis (PFGE) protocol was developed and
      applied to 50 isolates of the UK epidemic strain of Clostridium difficile,
      polymerase chain reaction (PCR) ribotype 001, to develop a PFGE-based subtyping
      scheme. This protocol overcame the inherent DNA degradation problems associated
      with typing this strain of C. difficile by this method, and whole genomic
      digestion with SmaI restriction enzyme yielded seven distinct and reproducible
      PFGE banding patterns. Modified PFGE is an appropriate method for subtyping C.
      difficile PCR ribotype 001 that could be used to improve epidemiological
      investigations.

PMID- 16002185
TI  - Incidence and effect of incorrect prescription and administration of nasal
      mupirocin for methicillin-resistant Staphylococcus aureus.

PMID- 16002186
TI  - Residual protein levels on reprocessed dental instruments.
AB  - Reduction of the initial bioburden on instruments, prior to sterilization, is
      believed to reduce transmission risks of iatrogenic Creutzfeldt-Jakob disease.
      Endodontic files are used in the preparation of root canals and are likely to
      have close contact and become contaminated with neural material from branches of
      the maxillary and mandibular cranial nerves. This study examined methods used by
      22 dental practices to clean endodontic files, and scored visible debris and
      residual protein levels adhering to 220 dental endodontic files that had been
      used, cleaned, autoclaved and were deemed ready for re-use. Visible debris was
      scored after examination under a dissecting light microscope. Residual protein
      was quantified using a fluorescent assay based on reaction of proteins with o
      phthaldialdehyde/N-acetyl cysteine. There was wide variation in the methods used
      by practices to clean endodontic files. The cleaning process varied from a wipe
      with an alcohol-impregnated cloth to hand scrubbing and/or use of an ultrasonic
      bath. Surface debris was visually detected on 98% of files. Residual protein was
      detected on all the files examined (median amount: 5.4 microg; range: 0.5-63.2
      microg). These results demonstrate that the cleaning of some instruments
      reprocessed routinely in primary care is incomplete, and such instruments cannot
      be excluded as a potential source of cross-infection.

PMID- 16002187
TI  - Roles for melanocortins and leptin in adipose tissue apoptosis and fat
      deposition.
AB  - Leptin has a wide range of effects on physiological functions related to the
      regulation of body energy balance. Many of leptin's effects are mediated through
      neuropeptide-containing neurons and neuropeptide receptors in the hypothalamus.
      The melanocortin system includes both agonist (alpha-melanocyte stimulating
      hormone, alphaMSH) and antagonist peptides (agouti related peptide, AGRP).
      Increased melanocortin receptor stimulation following leptin administration plays
      an important role in leptin-induced hypophagia and increased sympathetic nervous
      system activity and is partly responsible for leptin-induced weight loss.
      However, melanocortins do not appear to mediate some of the more striking
      centrally-mediated effects of leptin on adipose tissue, including adipose tissue
      apoptosis, that lead to the extensive depletion of fat.

PMID- 16002188
TI  - A comparison of immunohistochemical and silver staining methods for the detection
      of diffuse plaques in the aged canine brain.
AB  - Plaques and amyloid angiopathy represent frequent findings in the aging canine
      brain, whereas neuritic (senile) plaques and neurofibrillary tangles, the
      hallmark of Alzheimer's disease in humans, have only rarely been described in
      this species. Most studies on canine age-related CNS changes have used the
      modified (mod.) Bielschowsky method. Therefore, it remains to be determined,
      whether results obtained represent species-specific age-related changes or are
      due to the use of inappropriate methods. Consequently, the aim of this study was
      to compare the usefulness of various methods for the detection of age-related
      changes in the canine CNS. In a preliminary study, 130 brains from dogs between 1
      month and 18 years of age were screened for the presence of A-beta protein using
      a monoclonal antibody against the beta-amyloid peptide. Thereafter, 30 brains of
      aged dogs, 10-18 years of age, out of the 130, were comparatively investigated by
      immunohistochemistry and silver stains such as the method of Campbell-Switzer,
      Reusche, Gallyas, modified (mod.) Bielschowsky and mod. Bodian as well as the
      Congo red-stain. Vascular amyloid angiopathy, plaques and A-beta protein deposits
      in the hippocampus/dentate gyrus were an age-dependent process starting at the
      age of 8 years and increased in a linear fashion with age. In contrast, plaque
      density did not rise in a similar age-related fashion in aged dogs. Moreover,
      great individual variations were observed in aged animals. Immunohistology was by
      far the most sensitive method for detection of diffuse plaques and amyloid
      angiopathy, followed by the Campbell-Switzer, Reusche, mod. Bielschowsky, and
      mod. Bodian technique. Neurofibrillary tangles and Congo red positive neuritic
      plaques were not found with any method. Immunohistochemically, two plaque types,
      both resembling diffuse human plaques, occurring in the superficial or deep
      cortical layers, were detected. Cluster analysis suggested the presence of three
      subgroups such as aged dogs with a low, medium and high number of plaques.
      Summarized, detection of plaques depends strongly upon the method used and the
      aging canine brain displays diffuse plaques and amyloid angiopathy but lacks
      neurofibrillary tangles and classic/neuritic and Congo red positive plaques.
      Cluster analysis indicated, that genetic factors might be important as
      predisposition for the development of diffuse plaques in dogs. The observed
      findings substantiate previous observations, that the canine brain represents an
      important model to study the pathogenesis of diffuse plaques and amyloid
      angiopathy in the absence of other Alzheimer disease characteristic lesions.

PMID- 16002189
TI  - Evaluation of learning outcomes in a research process and the utilization of
      research knowledge from the viewpoint of nursing students.
AB  - The purpose of this descriptive study was to evaluate the learning that takes
      place in a research process of nursing students when writing their Bachelor's
      theses and to describe the learning outcomes in utilizing research knowledge. The
      sample comprised nursing students from a Finnish polytechnic. All of them worked
      with their Bachelor's theses. The data were collected by a questionnaire
      constructed for this study and 257 nursing students participated in the study.
      The data were analysed by SPSS 10.0 software. The students knew the steps of the
      research process moderately well. Most of the students responded that research
      results had been implemented in nursing practice. More than half of the students
      found the attitudes towards research positive in their clinical placements.
      Students' self-evaluation of learning outcomes was positive and they felt able to
      use research knowledge. The results indicated improving learning outcomes during
      the working process of the Bachelor's thesis. Working with the Bachelor's thesis
      is an effective way to lead the students to use research knowledge. The results
      are useful in guiding the students through their Bachelor's theses as well as in
      developing the curriculum and working life.

PMID- 16002190
TI  - Using QPCR to assign infectious potencies to adenovirus based vaccines and
      vectors for gene therapy: toward a universal method for the facile quantitation
      of virus and vector potency.
AB  - The assignment of infectious potency to test articles of adenovirus has been
      conducted mainly using classical end-point dilution methods, which rely on virus
      induced cytopathology to reveal the presence of infectious virus. These assays
      suffer the disadvantages of labor intensity, duration, throughput restriction and
      variability. In the course of our development of an Ad5 based HIV vaccine for
      clinical evaluation, we sought a facile method for the assignment of potency to
      the numerous test articles generated during the development of bioprocesses for
      bulk manufacture, downstream purification and formulation. In this paper we
      describe a quantitative PCR based potency assay (QPA) which uses QPCR to
      quantitate adenovirus genomes replicated 24h after the inoculation of a test
      article on 293 cell monolayers, and then relates that mass to potency by
      interpolation to a standard curve of replicated adenovirus genomes constructed
      with a reference adenovirus standard to which infectious potency has been
      previously assigned in the classical end-point dilution assay. The QPA assay for
      adenovirus is simple and rapid, with a throughput capacity adequate to the
      potency assay demands of bioprocess development, and with a precision expressed
      as a root variability of 16.8% R.S.D., allowing for close discriminations of the
      products of alternative process configurations. The adenovirus QPA principle can
      be applied to the quantitation of infectious potency of both RNA and DNA viruses
      and we report briefly on the development of QPA assays for measles and mumps. QPA
      assays owing to their simplicity and easy automation, rapidity, capacity and
      precision hold promise to become widely practiced methods for the quantitation of
      the potency of live virus vaccines and other recombinant virus vectors.

PMID- 16002191
TI  - Model selection methodology for inter-laboratory standardisation of antibody
      titres.
AB  - The aim of the European Sero-Epidemiology Network 2 (ESEN2) is to compare
      standardised serological results of vaccine preventable diseases across Europe.
      In order to adjust for laboratory and assay differences, the participant
      laboratories tested a standardisation panel for each disease and the results were
      plotted against those of a reference centre in order to obtain standardisation
      equations. We describe an algorithm for obtaining these equations which took into
      account outliers, censored data and model selection, and needed to be robust due
      to the variety of assays and diseases under investigation. If the standardisation
      equations explained sufficient variability, these were used to convert each
      country's main serum bank results to a common unitage, thereby allowing
      international comparisons to be made.

PMID- 16002192
TI  - Vaccination against foot and mouth disease reduces virus transmission in groups
      of calves.
AB  - The aim of vaccination during an epidemic of foot and mouth disease (FMD) is not
      to induce clinical protection, but to reduce virus transmission. Since no
      quantitative data were available on the effectiveness of vaccination in cattle,
      we investigated whether a single vaccination against FMD could reduce virus
      transmission in groups of calves by estimating the reproduction ratio R, i.e. the
      average number of secondary cases caused by one infectious animal in a
      susceptible population. We performed two experiments with six groups of either
      four vaccinated or four non-vaccinated calves each. Vaccination was carried out
      with O(1) Manisa vaccine. Two weeks after vaccination, two calves per group were
      inoculated intra-nasally with FMDV field isolate O/NET 2001. The two other calves
      were contact-exposed to the inoculated calves. Contact infections were observed
      by clinical inspection, virus isolation and RT-PCR on heparinised blood, oro
      pharyngeal fluid and probang samples and antibody response to non-structural
      proteins. In all six non-vaccinated groups, transmission to contact-exposed
      calves was recorded; in the vaccinated groups, virus transmission was observed to
      one contact-exposed calf. In the non-vaccinated groups R(c) was 2.52 and
      significantly above 1, whereas in the vaccinated groups R(v)=0.18 and
      significantly below 1, indicating that vaccination may successfully be applied as
      additional intervention tool to reduce virus transmission in a future epidemic of
      FMD.

PMID- 16002193
TI  - Protection of turkeys against Chlamydophila psittaci challenge by DNA and rMOMP
      vaccination and evaluation of the immunomodulating effect of 1 alpha,25
      dihydroxyvitamin D(3).
AB  - Plasmid DNA expressing the major outer membrane protein (MOMP) of an avian
      Chlamydophila psittaci serovar D strain and recombinant MOMP (rMOMP) with or
      without the immunomodulating adjuvant 1 alpha,25-dihydroxyvitamin D(3) have been
      tested for their ability to elicit an immune response and induce protection in
      turkeys against challenge with the same serovar. Three vaccination strategies
      were compared: priming and boosting with either pcDNA1::MOMP or rMOMP and priming
      with pcDNA1::MOMP followed by rMOMP boosting. Turkeys primed with pcDNA1::MOMP
      showed significant protection against Cp. psittaci challenge, turkeys primed with
      rMOMP did not. The steroid hormone 1 alpha,25-dihydroxyvitamin D(3) augmented
      serum and mucosal antibody titres. However, higher antibody titres were not
      related to better protection and even had a negative effect on especially
      bacterial excretion.

PMID- 16002194
TI  - An in situ postexposure feeding assay with Carcinus maenas for estuarine sediment
      overlying water toxicity evaluations.
AB  - This study developed and evaluated a short-term sublethal in situ toxicity assay
      for estuarine sediment-overlying waters, with the crab Carcinus maenas (L.) based
      on postexposure feeding. It consisted of a 48-h in situ exposure period followed
      by a short postexposure feeding period (30 min). A precise method for quantifying
      feeding, using the Polychaeta Hediste (Nereis) diversicolor Muller as food
      source, was first developed. The sensitivity of the postexposure feeding response
      was verified by comparing it to that of lethality, upon cadmium exposure. The
      influence of environmental conditions prevailing during exposure (salinity,
      temperature, substrate, light regime, and food availability) on postexposure
      feeding was also addressed. The potential of this in situ assay was then
      investigated by deploying organisms at ten sites, located in reference and
      contaminated Portuguese estuaries. Organism recovery ranged between 90% and 100%
      and a significant postexposure feeding depression (16.3-72.7%) was observed at
      all contaminated sites relatively to references.

PMID- 16002195
TI  - Religion and survival in a secular region. A twenty year follow-up of 734 Danish
      adults born in 1914.
AB  - The aim of the study was to analyse associations of religiosity and mortality in
      a secular region. The sample consisted of 734 Danish, community dwelling elderly
      persons, living in a secular culture, and all aged 70 when primary data were
      collected. Secondary data consisted of a 20 year follow-up on vital status or
      exact age of death. The study was designed to be highly comparable to studies
      conducted in more religious environments in order to compare results. Three
      variables of religion were investigated in relation to survival: importance of
      affiliation, church attendance and listening to religious media. Relative hazards
      (RH) of dying were controlled in models including gender, education, medical and
      mental health, social relations, help given and received, and health behaviour.
      The results showed significant and positive associations between claiming
      religious affiliation important and survival (relative hazard of dying=RH .70;
      95% CI .58-.85) and church attendance and survival (RH .73; 95% CI .64-.87).
      Results decreased and only stayed significant regarding church attendance when
      controlled for covariates. Nearly all significant effects were seen in women, but
      not in men. The effect size of the full sample is less than in more religious
      environments in United States samples. Although the positive overall RHs are
      comparable to those of other studies, the mediating variables and pathways of
      effects seem dissimilar in this sample from a secular environment. Receiving and
      especially giving help to others are suggested as variables of explanatory value.

PMID- 16002196
TI  - Social and psychological resources and health outcomes after the World Trade
      Center disaster.
AB  - Previous studies on community disasters tend to assess non-representative samples
      and use nonstandard measures of well-being. Additionally, few of these studies
      are longitudinal in design. In this report, we examine the consequences of the
      World Trade Center Disaster (WTCD) within a stress model perspective to assess
      level of exposure to the disaster and well-being after this event, as measured by
      the SF12 mental health and physical health scales. Data come from a two-wave
      panel study of 1681 English or Spanish speaking adults living in New York City on
      the day of the terrorist attacks and were collected by telephone interviews 1 and
      2 years after the disaster. In ordinary least-squares regression models that
      contained demographic characteristics, stress risk factors, and social
      psychological resources as independent variables, level of exposure to the
      disaster was associated with poorer Wave 2 physical well-being, but not
      psychological health. Level of disaster exposure was not related to Wave 2
      physical health, however, once the Wave 1 level of physical health was
      controlled, suggesting that disaster exposure did not have a lasting impact on
      variation in physical well-being. Results also indicated that experiencing a
      panic attack, negative life events, or traumatic events were related to poorer
      physical health. Respondents who met screening criteria for possible alcohol
      dependence post-disaster, experienced negative life events, or experienced
      traumatic events, were more likely to suffer from poorer mental health compared
      to those who did not meet the criteria, experience negative life events or
      experience traumas. We discuss these findings relative to community disasters in
      industrialized and developing countries.

PMID- 16002197
TI  - Patient characteristics and inequalities in doctors' diagnostic and management
      strategies relating to CHD: a video-simulation experiment.
AB  - Numerous studies examine inequalities in health by gender, age, class and race,
      but few address the actions of primary care doctors. This factorial experiment
      examined how four patient characteristics impact on primary care doctors'
      decisions regarding coronary heart disease (CHD). Primary care doctors viewed a
      video-vignette of a scripted consultation where the patient presented with
      standardised symptoms of CHD. Videotapes were identical apart from varying
      patients' gender, age (55 versus 75), class and race, thereby removing any
      confounding factors from the social context of the consultation or other aspects
      of patients' symptomatology or behaviour. A probability sample of 256 primary
      care doctors in the UK and US viewed these video-vignettes in a randomised
      experimental design. Gender of patient significantly influenced doctors'
      diagnostic and management activities. However, there was no influence of social
      class or race, and no evidence of ageism in doctors' behaviour. Women were asked
      fewer questions, received fewer examinations and had fewer diagnostic tests
      ordered for CHD. 'Gendered ageism' was suggested, since midlife women were asked
      fewest questions and prescribed least medication appropriate for CHD. Primary
      care doctors' behaviour differed significantly by patients' gender, suggesting
      doctors' actions may contribute to gender inequalities in health.

PMID- 16002198
TI  - The effect of lifetime victimization on the mental health of children and
      adolescents.
AB  - This paper examines the cumulative prevalence of victimization and its impact on
      mental health in a nationally representative sample of 2030 children aged 2-17 in
      the USA. Telephone interviews conducted with both caregivers and youth revealed
      socio-demographic variations in lifetime exposure to most forms of victimization,
      with ethnic minorities, those lower in socio-economic status, and those living in
      single parent and stepfamilies experiencing greater victimization. Sexual
      assault, child maltreatment, witnessing family violence, and other major violence
      exposure each made independent contributions to levels of both depression and
      anger/aggression. Other non-victimization adversities also showed substantial
      independent effects, while in most cases, each victimization domain remained a
      significant predictor of mental health. Results suggest that cumulative exposure
      to multiple forms of victimization over a child's life-course represents a
      substantial source of mental health risk.

PMID- 16002199
TI  - The future of antidepressant pharmacogenetics is arriving. Introduction.

PMID- 16002200
TI  - Anxiolytic-like effects of ginseng in the elevated plus-maze model: comparison of
      red ginseng and sun ginseng.
AB  - This study was performed to investigate the anxiolytic-like effects of red
      ginseng (RG, steamed raw ginseng at 98-100 degrees C) and sun ginseng (SG, heat
      processed ginseng at higher temperature) in mice using the elevated plus-maze
      model. Furthermore, the anxiolytic-like effects of RG and SG were compared to a
      known active anxiolytic drug (diazepam). The RG butanol fraction (100 mg/kg)
      significantly increased the number of open arms entries and the time spent on the
      open arm (indicators of anxiolytic-like effects) compared with that of the saline
      group. However, lower doses of the SG total extract (50 mg/kg) and the SG butanol
      fraction (25 and 50 mg/kg) significantly increased the number of open arms
      entries and the time spent on the open arms. The RG total extract (100 mg/kg) and
      the SG total extract at a lower dose (25 mg/kg) did not increase the number of
      open arm entries or the time spent on the open arm. On the other hand, the RG
      butanol fraction (100 mg/kg), the SG total extract (50 mg/kg), and the SG butanol
      fraction (50 mg/kg) decreased locomotor activity in a manner similar to diazepam.
      These data indicate that ginseng has anxiolytic-like effects, and the anxiolytic
      potential of SG is stronger than that of RG in the elevated plus-maze model.
      Ginseng saponins have been suggested to play an important role in the anxiolytic
      effects of ginseng. We provide evidence that ginseng may be useful for the
      treatment of anxiety.

PMID- 16002201
TI  - Health risks of dietary intake of environmental pollutants by elite sportsmen and
      sportswomen.
AB  - The dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb),
      hexachlorobenzene (HCB), polychlorinated naphthalenes (PCNs), polycyclic aromatic
      hydrocarbons (PAHs), polychlorinated diphenyl ethers (PCDEs), polybrominated
      diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) by elite sportsmen and sportswomen
      of Catalonia, Spain, was assessed. In 2000, food samples were randomly acquired
      in various cities of Catalonia. Analysis of the above pollutants were determined
      according to the appropriate analytical techniques (ICP-MS, HRGC/HRMS, HPLC). In
      general terms, elite sportsmen and sportswomen showed a higher intake of Cd, Hg,
      Pb, HCB, PCNs, PCDD/Fs and PAHs than the general population, while it was lower
      for PCDEs (both sexes), and PCBs and PBDEs (women). According to the FAO/WHO
      provisional tolerable weekly intake (PTWI) for metals, the WHO tolerable daily
      intake (TDI) for HCB, and the US EPA's reference dose (RfD) for PAHs, the dietary
      intakes of environmental pollutants should not mean a potential toxic hazard.
      However, the WHO-TDI for PCDD/Fs and "dioxin-like" PCBs is exceeded in sportsmen.
      The current results indicate that the consumption of those food groups showing
      the highest contribution to the intake of these pollutants should be diminished.
      In relation to this, the reduction of the consumption of dairy products and
      cereals would be important.

PMID- 16002202
TI  - Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly decreases the expression of
      perforin, granzyme A and granulysin in human NK-92CI cell line.
AB  - Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte
      (CTL) cells kill target cells by the directed release of cytolytic granules that
      contain perforin, granzymes and granulysin. We previously have found that
      dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide
      significantly inhibited NK, LAK and CTL activities via the inhibition of granzyme
      activity. To further explore the mechanism of organophosphorus pesticide-induced
      inhibition of cell-mediated cytolysis, we asked here whether organophosphorus
      pesticides affect the expression of perforin, granzyme and granulysin in NK
      cells. We used NK-92CI cell, an interleukin-2 (IL-2) independent human NK cell
      line. We confirmed that NK-92CI cells express CD56 surface marker, perforin,
      granzyme A and granulysin by flow cytometry and immunofluorescence microscope,
      and that it is highly cytotoxic to K562 cells in chromium release assay. We found
      that DDVP significantly decreases the expression of perforin, granzyme A and
      granulysin in NK-92CI cells in a dose-dependent manner. Immunocytochemical
      results showed that DDVP significantly decreases perforin, granzyme A and
      granulysin positive granules in NK-92CI cell, which may be due to the
      degranulation. We also found that DDVP have a modest, but a significant
      inhibitory effect on the transcription of mRNA of perforin, granzyme A and
      granulysin.

PMID- 16002203
TI  - Incorporation of carotenoid esters into liposomes.
AB  - Carotenoid esters are investigated for their interaction with liposomal membranes
      and compared with their corresponding free (non-esterified) carotenoids. A
      monoester (beta-cryptoxanthin) and two diesters (zeaxanthin and lutein) were
      chosen. Egg yolk phosphatidylcholine liposomes served as the membrane model. We
      measured the sizes of the liposomes by photon correlation spectroscopy. The
      incorporation yields were determined spectrophotometrically. From liposomes
      simultaneously doped with the fluorescent dye Laurdan, fluidity changes of the
      liposomes were obtained. In summary, the results indicate that the carotenoid
      esters: (i) get incorporated, but at a lower yield than their corresponding free
      carotenoids, (ii) also increase the membrane rigidity as do the free carotenoids,
      and (iii) increase the liposome sizes significantly, but after extrusion through
      an 0.1 mum filter the sizes resemble with the exception of the liposomes
      incorporated with lutein diesters, they remain bigger indicating an elastic
      property due to two different accessible locations in the membrane.

PMID- 16002204
TI  - Effectiveness of early pelvic floor rehabilitation treatment for post
      prostatectomy incontinence.
AB  - PURPOSE: Urinary incontinence after radical prostatectomy is a significant
      clinical problem. In this prospective study we investigate the effectiveness of
      early pelvic floor muscle training (PFMT) on a large population, that had
      undergone radical retropubic prostatectomy (RRP) at our department. METHODS: 300
      consecutive patients who had undergone RRP for clinically confined prostate
      cancer were randomized in two groups after catheter removal. One group of 150
      patients took part in a structured PFMT program. This began before discharge and
      consisted of Kegel exercises. The remaining 150 patients constituted the control
      group, they were not formally instructed in PFMT. Incontinence was assessed
      objectively using the 1 hour and 24 hour pad test, as well as with the ICS-Male
      questionnaire. All patients who were incontinent after 6 months underwent
      urodynamic evaluation. RESULTS: In the treated group, 19% (29 patients) achieved
      continence after 1 month, and 94.6% (146 patients) after 6 months. In the control
      group 8% (12 patients) achieved continence after 1 month, and 65% (97 patients)
      after 6 months (p<0.001). Patient age did not correlate with continence in the
      control group (p>0.05), although a significant correlation was revealed within
      the treated group (p<0.01). Overall, 93.3% of the total population achieved
      continence after one year. CONCLUSIONS: After RRP an early supportive
      rehabilitation program like PFMT significantly reduces continence recovery time.

PMID- 16002205
TI  - Glucose-induced lipogenesis in pancreatic beta-cells is dependent on SREBP-1.
AB  - High concentrations of glucose induce de novo fatty acid synthesis in pancreatic
      beta-cells and chronic exposure of elevated glucose and fatty acids synergize to
      induce accumulation of triglycerides, a phenomenon termed glucolipotoxicity. Here
      we investigate the role of sterol-regulatory element binding proteins in glucose
      induced lipogenesis in the pancreatic beta-cell line INS-1E. We show that glucose
      induces SREBP-1c expression and SREBP-1 activity independent of insulin secretion
      and signaling. Using adenoviral expression of SREBP-1c and a SREBP-mutant we show
      that lipogenic gene expression, de novo fatty acid synthesis and lipid
      accumulation are induced primarily through sterol-regulatory elements (SREs) and
      not E-Boxes. Adenoviral expression of a dominant negative SREBP compromises
      glucose induction of some lipogenic genes and significantly reduces glucose
      induction of de novo fatty acid synthesis. Thus, we demonstrate for the first
      time that SREBP activity is necessary for full glucose induction of de novo fatty
      acid synthesis in pancreatic beta-cells.

PMID- 16002206
TI  - Interleukin-18 is expressed in rat testis and may promote germ cell growth.
AB  - Although host-defence mechanisms, designed to preserve the integrity of the
      developing germ cells are operative in the testis, the components of this
      protective system have yet to be characterised in detail. Here, we report that
      the cytokine interleukin-18 (IL-18) is expressed in the rat testis and may
      contribute to these defences. Thus, analysis by RT-PCR and Western blotting
      revealed pronounced testicular expression of pro-IL-18 from postnatal day 5 and
      onwards. Expression of both IL-18 mRNA and protein was found to be localised to
      meiotic and post-meiotic germ cells as evaluated by in situ hybridisation and
      immunohistochemistry, respectively. The mRNA species coding for the IL-18
      receptor and IL-1beta converting enzyme, which activates pro-IL-18, were also
      shown to be expressed by the seminiferous tubules. Recombinant IL-18 was seen to
      stimulate spermatogonial DNA synthesis in cultures of staged segments of rat
      seminiferous tubules, without influencing germ cell apoptosis. These results
      suggest that IL-18 may have host-protective and growth-promoting functions in the
      testis, but further investigations need to be done to confirm this.

PMID- 16002207
TI  - Cytogenetic profiles as additional markers to pathological features in clinically
      localized prostate carcinoma.
AB  - Fluorescence in situ hybridization analysis for evaluation of 7, 8, X chromosomes
      and EGFR, LPL, MYC, AR genes in 79 neoplastic foci from 56 patients with
      clinically localized prostate cancer was performed. We found aneusomy for
      chromosome 7, 8 and X in 74/77 (96.1%), 56/76 (73.7%), 26/70 (37.1%) of examined
      foci respectively. No specimen was amplified for EGFR and AR genes, only 2/71
      (2.8%) specimens showed MYC gene amplified. LPL deletion was present in 52/76
      (68.4%) specimens. Statistically association between Gleason score and both
      chromosome 7 aneusomy and 8p21 deletion was present. The frequency of chromosome
      7 aneusomy was statistically higher in T3-4 cases than T2c and T2a-T2b ones. We
      considered as unfavorable a genetic set if aneusomy for at least two chromosomes
      and one altered gene were present. The percentage of tumors, with unfavorable
      genetic pattern, increased from 36.4 to 75.0% in those with Gleason >7 and from
      40.0 to 73.7% in those with stage T3 or more. These alterations could be
      considered potent genetic markers adjunctive to conventional prognostic
      parameters. Our objective was to establish specific genetic profiles which may
      discriminate favorable and unfavorable genetic prognosis tumors.

PMID- 16002208
TI  - beta-Tubulin mutations in ovarian cancer using single strand conformation
      analysis-risk of false positive results from paraffin embedded tissues.
AB  - Mutations in the beta-tubulin gene have been proposed as a resistance mechanism
      to paclitaxel. We therefore investigated the presence of mutations in the beta
      tubulin M40 gene in 40 ovarian tumours (16 paraffin-embedded and 24 freshly
      frozen) selected for good or poor response to chemotherapy with paclitaxel or non
      tubulin-affecting regimens. The presence of mutations was investigated using
      single strand conformation analysis followed by sequencing of the products with
      altered mobility. No sequence variants in the exons of the beta-tubulin M40 gene
      were detected. Non-reproducible shifts were identified, in eight out of 16
      paraffin embedded samples. This may explain some of the previously published
      discrepancies. In conclusion, sequence variants in the beta-tubulin M40 gene are
      rare and are unlikely to be a clinically relevant explanation of resistance to
      paclitaxel.

PMID- 16002209
TI  - Tumor hypoxia and cancer progression.
AB  - Aerobic life consumes oxygen for efficient production of high energy compounds.
      The ability to sense and respond to changes in oxygen partial pressure represents
      a fundamental property to assure the cellular oxygen supply to be within a narrow
      range that balances the risks of oxidative damage vs. oxygen deficiency. The
      discovery of hypoxia-inducible factor-1 (HIF-1) allowed the identification of
      molecular mechanisms by which changes in oxygenation are transduced to adequate
      intracellular adaptive responses. It became apparent that hypoxia can initiate
      cell demise by apoptosis/necrosis but also prevent cell death by provoking
      adaptive responses that, in turn, facilitate cell proliferation or angiogenesis,
      thus contributing to tumor progression. Considering that activation of HIF-1
      provokes pro-survival as well as pro-death decisions under hypoxia, it will be
      crucial to understand decision making processes in regulating cell death,
      adaptation and chemoresistance. Likely, secondary stressors such as pH changes,
      i.e. acidosis, and the context of genetic alterations will shape the role of HIF
      1 to affect susceptibility of cells to undergo hypoxia-induced cell death or to
      allow adaptation and progression towards malignancy. Understanding the mechanisms
      by which HIF-1 affects the expression and/or function of key apoptotic regulators
      such as Bcl-2 family members or p53 will help to uncover how HIF-1 induces cell
      death and the manner in which cells can overcome such signals and thus determine
      which of its Janus faces prevail.

PMID- 16002210
TI  - Decomposition of phenol by hybrid gas/liquid electrical discharge reactors with
      zeolite catalysts.
AB  - Application of hybrid gas/liquid electrical discharge reactors and a liquid phase
      direct electrical discharge reactor for degradation of phenol in the presence and
      absence of zeolites have been investigated. Hybrid gas/liquid electrical
      discharges involve simultaneous high voltage electrical discharges in water and
      in the gas phase above the water surface leading to the additional OH radicals in
      the liquid phase and ozone formation in the gas phase with subsequent dissolution
      into the liquid. The role of applied zeolites, namely NH4ZSM5, FeZSM5 and HY,
      were also studied. Phenol degradation and production of primary phenol by
      products, catechol and hydroquinone, during the treatment were monitored by HPLC
      measurements. The highest phenol removal results, 89.4-93.6%, were achieved by
      electrical discharge in combination with FeZSM5 in all three configurations of
      corona reactors. These results indicate that the Fenton reaction has significant
      influence on overall phenol removal efficiency in the electrical discharge/FeZSM5
      system due to the additional OH radical formation from hydrogen peroxide
      generated by the water phase discharge.

PMID- 16002211
TI  - Biodegradation of redox dye Methylene Blue by up-flow anaerobic sludge blanket
      reactor.
AB  - The objective of this study is to evaluate the decolorization of Methylene Blue
      (MB) by an up-flow anaerobic sludge blanket (UASB) reactor. The UASB reactor was
      operated under batch condition with total treatment volume of 3l and operation
      time of 24 h per batch. It was found that the color of MB disappeared within a
      few minutes after entering into the UASB reactor due to reduction by anaerobic
      biomass. However, the reduced MB was re-oxidized again by air after discharged
      from the reactor and thus caused low color removal efficiency. The presence of
      suitable amount of organic content (sucrose and peptone) as an electron donor
      played an important factor for color removal. It was observed that more than 90%
      of color removal efficiency was achieved in the UASB reactor with 0.627 mmoll(-1)
      of MB concentration and the presence of low amount of organic content (<0.45 g
      COD/(ld)). Biological dye reduction kinetics depends on the concentration of dye
      and reducing equivalents. The kinetic behavior of MB biodegradation by microbes
      was also investigated to determine the model involved in the process.

PMID- 16002213
TI  - A study of a dendritic marker, microtubule-associated protein 2 (MAP-2), in rats
      neonatally treated neurosteroids, pregnenolone and dehydroepiandrosterone (DHEA).
AB  - Neurosteroids administered during the neonatal period affect the development of
      several brain systems. We examined the effects of neonatal treatment with
      pregnenolone and dehydroepiandrosterone (DHEA) on a marker of neuronal dendrites,
      microtubule-associated protein 2 (MAP-2), in rat brain. Neonatal treatment with
      pregnenolone and DHEA increased the expression of MAP-2 in the hippocampus and
      nucleus accumbens but not in the prefrontal cortex, striatum or amygdala in
      adulthood.

PMID- 16002212
TI  - Increased levels of Homer1b/c and Shank1a in the post-synaptic density of spinal
      dorsal horn neurons are associated with neuropathic pain in rats.
AB  - Activity-dependent plasticity in the spinal dorsal horn may underlie the
      development of neuropathic pain following peripheral nerve injury. In this study
      we examined whether the expression and loss of behavioral signs of neuropathic
      pain were associated with changes in the content of the scaffolding proteins
      Homer and Shank in the post-synaptic density (PSD) of the spinal dorsal horn. In
      animals exhibiting thermal hyperalgesia and differential weight-bearing behavior
      7 days after loose ligation of the sciatic nerve the levels of Homer1b/c and
      Shank1a were significantly greater than in control, uninjured or sham-operated
      animals. These greater levels were specifically a reflection of increases in the
      injured, ipsilateral and not contralateral dorsal horn. In contrast, there were
      no differences in the PSD content of Homer1b/c and Shank1a in the dorsal horn of
      control or sham-operated animals and ligated animals in which the thermal
      hyperalgesia and differential weight-bearing behavior had disappeared 28 days
      after the loose ligation. These data revealed a close association between the
      expression and loss of allodynia and hyperalgesia with changes in the levels of
      Homer1b/c and Shank1a in the spinal dorsal horn. The reversible shift in the
      content of scaffolding proteins in the PSD may have important implications for
      the development of injury-elicited neuropathic pain.

PMID- 16002214
TI  - Upregulated and prolonged differentiation potential of the ependymal cells lining
      the ventriculus terminalis in human fetuses.
AB  - The ventriculus terminalis (VT) is a dilated cavity within the conus medullaris
      of the spinal cord. Although the VT was discovered in the mid-nineteenth century,
      little is known about its characteristics during development in human fetuses.
      Ependymal cells lining the cavities within the CNS retain high differentiation
      potential, and are believed to be responsible for the postnatal neurogenesis. To
      evaluate the differentiation capacity of the ependymal cells lining the VT during
      development, we examined glial fibrillary acidic protein (GFAP) and proliferating
      cell nuclear antigen (PCNA) expression in the spinal cord of 18-24-week-old human
      fetuses. GFAP is a marker for the degree of ependymal cell differentiation in the
      human fetus, and PCNA is a well-known marker for cell division. Morphological
      characteristics of the VT were also examined. At the lower portion of the conus
      medullaris, the central canal abruptly expands dorsally to become the VT. Then
      the VT widens bilaterally while its anteroposterior diameter reduces gradually in
      a caudal direction. Finally, the VT becomes a narrow, transverse slit at the
      level of the lowermost conus medullaris. Compared with those lining the central
      canal, more numerous ependymal cells lining the VT showed more intensive GFAP and
      PCNA expression throughout all gestational ages examined. This suggests that, in
      the developing human spinal cord, ependymal cells lining the VT retain their
      differentiation potential, including a higher proliferative capacity, until a
      later stage of development than those lining the central canal.

PMID- 16002215
TI  - Uncertainty, anxiety, and brain oscillations.
AB  - Influence of anxious expectation on spectral power and delta-gamma coupling was
      studied in 39 subjects (27 females) aged 19-30 years who also filled out the
      State Trait Anxiety Inventory. The situation of uncertainty was associated with
      general increase in spectral power of all EEG bands, which was particularly
      pronounced in high-trait anxiety subjects. In low-trait anxiety subjects,
      association between delta and gamma power significantly increased when they had
      to expect bad news but did not change when they expected good news. In high-trait
      anxiety subjects, this association tended to increase in both cases. Higher
      baseline delta power predicted higher gamma power in the situation where a bad
      news was expected. These findings are discussed in terms of Gray and McNaughton's
      theory of anxiety and evolutionary interpretation linking delta oscillations with
      reward motivation. Increase of delta-gamma coupling in anxiogenic situation is
      interpreted to reflect higher cortical arousal, which appears in a frustrating
      situation in subjects with higher activity of "motivational" delta system.

PMID- 16002216
TI  - Inhibition of histone deacetylation by trichostatin A intensifies the
      transcriptions of neuronal c-fos and c-jun genes after kainate stimulation.
AB  - Kainate stimulation induces the expression of immediate early genes, c-fos and c
      jun genes. Trichostatin A (TSA), a potent histone deacetylase (HDAC) enzyme
      inhibitor was used to test the role of histone hyperacetylation in the
      transcriptional regulation of c-fos and c-jun genes in neuronal cells in vivo and
      in vitro. Intraperitoneal administration of TSA increased histone H4 acetylation
      in hippocampi. Mice pretreatment with TSA were injected with kainic acid
      intraperitoneally and sacrificed over a time course of 12 h. Northern blot
      analysis and in situ hybridization showed that TSA pretreatment caused an
      increase in pre-existing basal levels of c-jun at 0 h and also intensified the
      maximal expression of both genes especially in the pyramidal layers of the
      hippocampus, thus demonstrating the inhibition of HDACs subsequently led to
      histone hyperacetylation to increase these genes expressions. TSA did not prolong
      the expression of c-fos or c-jun gene, in contrary to what we expected. Primary
      hippocampal neuron cell culture also displayed a similar pattern of c-fos and c
      jun mRNA enhancement with trichostatin A pretreatment. This study demonstrated
      that inhibition of histone deacetylation by TSA in neuronal cells affect the
      expressions of c-fos and c-jun genes, suggesting histone acetylation might play a
      role in the regulation of both genes expressions after kainate stimulation.

PMID- 16002217
TI  - Genetic association of alpha2-Heremans-Schmid glycoprotein polymorphism with late
      onset Alzheimer's disease in Italians.
AB  - Alpha2-Heremans-Schmid glycoprotein (AHSG), also known as fetuin-A, is a highly
      glycosylated protein which has been recently reported to be decreased in the
      cerebrospinal fluid of patients with Alzheimer's disease. AHSG is genetically
      polymorphic and two common alleles, AHSG*1 and AHSG*2, have been described. The
      purpose of this study was to investigate the distribution of AHSG gene
      polymorphism in 235 Caucasian Italian patients with late-onset Alzheimer's
      disease (LOAD) and 235 age- and gender-matched healthy controls. In patients with
      LOAD, the genotype distribution was 184 AHSG 1*1, 44 AHSG 1*2, 7 AHSG 2*2, and
      was significantly different from that observed in the 235 control subjects (117
      AHSG 1*1, 103 AHSG 1*2, 15 AHSG 2*2) (chi(2)=41.50, P<0.0001). After allowance
      for age, gender and APOE epsilon4 status, multivariate logistic regression
      analysis revealed that the adjusted odds ratio for the development of LOAD in
      AHSG 1*1 homozygotes was 3.90 (95% CI: 2.58-5.90, P<0.0001). These results
      suggest that the AHSG gene polymorphism may be associated with LOAD in Italians.
      Additional studies are warranted to examine the biological relevance of AHSG in
      the pathophysiology of neurodegenerative disorders.

PMID- 16002218
TI  - A role for GABAA receptors in the modulation of Paramecium swimming behavior.
AB  - The presence in Paramecium of gamma-aminobutyric acid A-type receptors (GABA(A))
      and the capability of the protozoon to synthesize and release the GABA
      neurotransmitter into the environment have already been demonstrated. This study
      investigates the involvement of the GABA(A) complex in the swimming control of
      the ciliated protozoon. The GABA(A) receptors were pharmacologically activated by
      the selective agonist muscimol and the effect on Paramecium primaurelia swimming
      behavior was analyzed. Paramecium normally swims forward, but the activation of
      GABA(A) receptors induced a peculiar response, characterized by alternate periods
      of whirling and forward swim. This effect was inhibited by the GABA(A) selective
      antagonists bicuculline and picrotoxin in a dose-dependent manner. Moreover, the
      application of benzodiazepines did not enhance the agonist action but only
      reduced it. Response to muscimol was also suppressed by nimodipine, a selective
      antagonist of dihydropyridine-sensitive calcium channels. This inhibition
      suggests that an inflow of calcium ions through L-type channels mediates the
      muscimol-induced swimming behavior.

PMID- 16002219
TI  - Hydroxysafflor yellow A protects rat brains against ischemia-reperfusion injury
      by antioxidant action.
AB  - The present study was conducted to investigate whether hydroxysafflor yellow A
      (HSYA) has a protective effect on brain injury after focal cerebral ischemia
      reperfusion, and to determine the possible mechanism. Behavioral tests were used
      to evaluate the damage to central nervous system. The infarct volume of brain was
      assessed in brain slices stained with 2% solution of 2,3,5-triphenyl tetrazolium
      chloride (TTC). Adult male Wistar rats were subjected to 2h of middle cerebral
      artery occlusion and 24h of reperfusion. Spectrophotometric assay was used to
      determine the content of malondialdehyde (MDA), and the activity of total
      antioxidative capability (T-AOC) and superoxide dismutase (SOD). The results
      showed that treatment with HSYA (2, 4, 8 mg/kg, i.v.) significantly decreased
      neurological deficit scores and reduced the percentage of infarction in the
      ipsilateral hemisphere compared with the model group. At the same time, HSYA
      treatment significantly attenuated the elevation of MDA content, the decrease in
      SOD activity, and the T-AOC in the ipsilateral hemisphere and serum. All of these
      findings suggest that HSYA might provide neuroprotection against cerebral
      ischemia/reperfusion injury through its antioxidant action.

PMID- 16002220
TI  - Increased c-Fos expression in the medial part of the lateral habenula during cue
      evoked heroin-seeking in rats.
AB  - Conditioned environmental stimuli are known to be important determinants of drug
      seeking behavior. c-Fos, the protein product of the protooncogene c-Fos, is
      expressed in neurons when there are drug-associated cue-induced drug-seeking
      behaviour. Therefore, its expression could serve as a marker of regional neuronal
      activation. Using an extinction/reinstatement paradigm of relapse animal model,
      we trained Sprague-Dawley rats to nose-poke for i.v. heroin (0.05 mg/kg/infusion)
      either daily for 4h or 25 infusions for 14 consecutive days. We then tested these
      animals for cue-evoked heroin-seeking behavior after abstinence from self
      administration of heroin for 14 days. Expression of c-Fos was examined in the
      lateral habenula (LHb), a region important for conveying information between the
      limbic forebrain and midbrain. Findings showed that heroin-associated conditioned
      stimuli could induce robust heroin-seeking behavior that was associated with
      increased c-Fos immunoreactivity in the medial part of the LHb. This observation
      suggests the involvement of the LHb in mediating drug cue-induced heroin-seeking
      behavior after abstinence from self-administration of heroin.

PMID- 16002221
TI  - Radiotherapy to patients with artificial cardiac pacemakers.
AB  - BACKGROUND: The in vitro studies show that the modern cardiac pacemakers
      utilising the complementary metal-oxide semi-conductor (CMOS) circuitry can be
      adversely affected by therapeutic radiation. However, the published clinical data
      are sparse regarding the safety of radiotherapy delivery to patients with
      artificial pacemakers. Despite the potential risk of life threatening
      complications, there are no national guidelines and most radiotherapy departments
      have no formal clinical risk management strategy in place. A literature review
      was performed to assess the risks involved in irradiating patients with
      pacemakers and to identify strategies, which minimise the risk of pacemaker
      malfunction. Recommendations for radiotherapy departments are made. CONCLUSION:
      Modern multi-programmable pacemakers are very sensitive to therapeutic
      megavoltage irradiation. There is no safe radiation threshold for megavoltage
      radiation. The low energy kilovoltage X-rays used for radiotherapy simulation
      cause no pacemaker malfunction. Megavoltage radiation can be safely delivered to
      patients with cardiac pacemakers provided direct irradiation of pacemakers is
      avoided, adequate monitoring is done during and after irradiation, and the dose
      to the pacemaker generator is kept below 2 Gy. Close liaison with cardiologists
      and a pacemaker clinic is essential and radiotherapy departments should have
      protocols in place to identify and care for cancer patients with pacemakers.

PMID- 16002222
TI  - Neurasthenia, subjective health complaints and sensitization.
AB  - Patients (n=997) visiting general practitioners in an area in Western Norway
      completed a battery of questionnaires related to subjective health complaints and
      fatigue. An additional 78 patients were referred directly to the hospital for
      neurasthenia. After screening the questionnaires and interviews with a selected
      sample, a total of 73 patients were finally accepted as 'neurasthenia' patients
      satisfying the ICD-10 diagnosis. These patients were compared with the remaining
      1002 patients. Patients with neurasthenia had more prevalent and more severe
      subjective health complaints, particularly pseudoneurological and musculoskeletal
      complaints than the reference population of patients. They reported low levels of
      instrumental coping and poorer physical fitness, in spite of a comparable level
      of self reported physical activity and exercise. Women were over-represented in
      this group. This overall higher score on subjective complaints from all organ
      systems is in accordance with the hypothesis of an overall and general
      sensitization to the afferent inputs from their psychophysiological systems.

PMID- 16002223
TI  - Stress-induced changes in human salivary alpha-amylase activity -- associations
      with adrenergic activity.
AB  - The salivary enzyme alpha-amylase has been proposed to indicate stress-reactive
      bodily changes. A previous study by the authors revealed marked increases in
      salivary alpha-amylase following psychosocial stress, indicating a stress
      dependent activation of salivary alpha-amylase. Salivary alpha-amylase has been
      suggested to reflect catecholaminergic reactivity. Our aim was to assess/evaluate
      a possible relationship between salivary alpha-amylase and adrenergic parameters,
      i.e. catecholamines, as well as other stress markers. Using an intra-individual
      repeated measures design, 30 healthy young men underwent the Trier Social Stress
      Test (TSST), which consists of a mental arithmetic task and free speech in front
      of an audience and a control condition in randomized order. Salivary alpha
      amylase and salivary cortisol as well as plasma catecholamines and cardiovascular
      activity were repeatedly measured before, during, and after both conditions.
      Significant differences were found between the stress and the rest condition in
      salivary alpha-amylase, salivary cortisol, plasma catecholamines, and
      cardiovascular parameters (heart rate, LF, HF, LF/HF). However, general alpha
      amylase responses (area under the curve) were not associated with general
      responses in catecholamines and cortisol in the stress condition (r smaller than
      0.25 for all analyses). Analysis of cardiovascular parameters indicates a
      positive relationship between amylase and sympathetic tone (LF/HF) during stress.
      Salivary alpha-amylase is sensitive to psychosocial stress. Since it does not
      seem to be closely related to other biological stress markers such as
      catecholamines and cortisol, salivary alpha-amylase may be a useful additional
      parameter for the measurement of stress.

PMID- 16002224
TI  - Distal and proximal factors related to aggression severity among patients in
      substance abuse treatment: family history, alcohol use and expectancies.
AB  - This study examined the relationships among distal (paternal and maternal family
      history of alcohol problems and violence) and proximal (general alcohol use,
      acute use associated with conflict incidents, alcohol-aggression expectancies)
      factors and physical aggression severity among 125 men and 125 women recruited
      from substance abuse treatment. Paternal alcohol problem history (PA) was related
      to alcohol-aggression expectancies, but no family history factors were related to
      general or acute alcohol use. Separate analyses examining predictors of
      aggression were conducted, one with general alcohol use and one with acute
      alcohol use. In both analyses, alcohol use and the maternal violence (MV) by PA
      interaction were significant. Specifically, MV was associated with aggression
      severity for those with a history of PA. The general alcohol use model also
      revealed significant alcohol by expectancy and MV by gender interactions. The
      findings suggest that expectancies are not the primary mediator of the alcohol
      aggression relationship, alcohol use measurement issues may impact whether
      expectancies are observed to moderate the alcohol-aggression relationship, and
      that both maternal and paternal family history factors appear to impact
      aggression severity.

PMID- 16002225
TI  - Ancient Egyptian doctors and the nature of the biblical plagues.
AB  - Paragraph 55 of the London Medical Papyrus describes burns derived from red
      waters and which later became infected with larvae in the wounds. The prescribed
      treatment for the burn is unusual as it calls for no rinsing and requires
      bandaging with alkaline materials only. Refraining from washing in the Nile (the
      single most readily available source of water in ancient Egypt), and the use of
      alkali-neutralizing agents indicates that the red caustic waters came from the
      river, and were acid in nature. A red, acid Nile is consistent with the first
      biblical plague of Egypt, which killed fish, and kept people from drinking from
      the river. In turn, the sulfate-laced waters of the medical document also offer a
      plausible insight into the subsequent biblical plagues. Amphibians would have
      stayed away from the deadly river, left to die on the banks, just as described in
      the second biblical plague. Similarly, the larvae in the wounds mentioned by the
      medical document re-echo the third and fourth biblical plagues: the kinnim
      invertebrates and the subsequent 'arob (varied insects) are consistent with
      larvae and the subsequent adults thereof. In pre-industrial Ancient Egypt,
      sulfates from a massive volcanic fall out provide the simplest and most
      exhaustive origin for such waters. A massive precipitation that would account for
      the waters in the medical document and the biblical texts is known from sediments
      at the bottom of lakes along the Nile Delta. The site is downwind from the island
      of Santorini, and the deposit of volcanic ashes took place during the Middle
      Bronze Age, i.e. at a time consistent with the eruption at the Greek volcanic
      island.

PMID- 16002226
TI  - Epilepsy and psychiatry: automatic psychic paroxysms.
AB  - This study analyzes diverse psychic phenomena which, although always occurring
      with very characteristic clinical features, are sometimes diagnosed as epilepsy
      and sometimes as symptoms of different psychiatric disorders depending on the
      availability of an electroencephalogram. It is posited that these phenomena,
      whenever they are accompanied by the features characteristic of an epileptic
      consciousness (suddenness, automatic nature, great intensity and a strong
      sensation of strangeness) should be diagnosed as partial seizures with a psychic
      content, regardless of the availability of an EEG. The co-occurrence of these
      four clinical signs, which are relatively simple to objectivize, is a more
      reliable clinical criterion for diagnosis than a transcraneal
      electroencephalogram, which, as is known, is of little value in measuring the
      electrical activity of partial seizures. Moreover, an interpretation of this type
      makes it possible to reconcile scientific data from various neurosciences which
      thus far have seemed contradictory.

PMID- 16002227
TI  - Combining RNA interference with PTD-fusion transcription factors: a novel
      integrated strategy for achieving trans-differentiation of adult stem cells?

PMID- 16002228
TI  - Forgiveness: a neurological model.
AB  - A definition of "forgiveness" is chosen that emphasizes its biological and
      neurological components, namely the cessation of emotions connected with memories
      of a hurtful act. An experience of forgiveness is analyzed into seven steps and
      each is associated with a neurological source. The cornerstone hypothesis is
      that, before forgiveness takes place, memories periodically arouse fear stemming
      from the amygdala. This fear drives a pattern of anger and fight-or-flight
      readiness. Under appropriate circumstances the frontal cortex interrupts the
      pattern and quells the fear response in the amygdala. The resultant relaxation of
      muscular tension signals the cortex that forgiveness has occurred. In addition,
      the memory pathway from the rhinal cortex and hippocampus to the amygdala is
      inhibited. Finally, a tangible act confirms that the memories no longer stimulate
      the amygdala and the pattern of anger and stress do not recur. The relationship
      of the neurological model with other theoretical models is presented and some
      avenues for experimental testing of the model are mentioned.

PMID- 16002229
TI  - Potential role for Eicosanoids originating from the ecto-lysophosphate
      phosphatase activity as a pro-inflammatory signal.

PMID- 16002230
TI  - Egg-sharing in return for subsidized fertility treatment--an ethically
      justifiable and practical solution to overcome the shortage of donor oocytes for
      therapeutic cloning.

PMID- 16002231
TI  - Self-medication with antibiotics: a possible cause of bacterial resistance.

PMID- 16002232
TI  - Oxygen as a therapy for reducing nicotine withdrawal symptoms.
AB  - Nicotine addiction leads to withdrawal symptoms in many persons who quit smoking.
      In addition to craving, the most commonly experienced symptoms are: depression;
      difficulty sleeping; irritability, frustration, or anger; anxiety; difficulty
      concentrating; restlessness; decreased heart rate; and increased appetite or
      weight gain. The severity of withdrawal symptoms are variable, and often lead to
      relapse. By altering the course of withdrawal symptoms it is possible to improve
      the chances of the quit attempt and reduce the risk of relapse. There is strong
      evidence that dopamine is the primary neurotransmitter in the reward pathway in
      addiction. The use of nicotine replacement therapies and Zyban (sustained release
      bupropion hydrochloride), both of which are suspected of exploiting dopamine's
      role in addiction, enhance the likelihood of long-term smoking cessation.
      Anecdotal reports of oxygen's capacity to reduce both the desire for nicotine and
      withdrawal symptoms suggest that this may be a therapeutic possibility for those
      who do not experience success with more traditional cessation approaches. Oxygen
      may have a favorable effect on nicotine withdrawal, as it appears to alter the
      balance of central neurotransmitters such as dopamine.

PMID- 16002233
TI  - Association between obesity and multiple myeloma in postmenopausal women may be
      attributed to increased aromatization of androgen in adipose tissue.

PMID- 16002234
TI  - Possible involvement of the BDNF-dependent pathway in treatment-emergent
      suicidality or decreased response to antidepressants.
AB  - Antidepressants are the main biological treatment for major depression. However,
      a substantial proportion of depressed patients do not improve clinically despite
      appropriate treatment and, in rare cases, antidepressants can induce or increase
      suicidal tendencies. These phenomena are more commonly found in young patients.
      The causes underlying treatment-emergent suicidality or poor response to
      antidepressants are still unknown. Animal and postmortem studies have
      demonstrated that antidepressants increase central brain-derived neurotrophic
      factor (BDNF) levels and activate the BDNF-tyrosine kinase receptor B (TrkB)
      pathway, which plays an important role in their therapeutic mechanism. In this
      report, several possible mechanisms relating to the BDNF-dependent pathway are
      proposed to account for treatment-emergent suicidality and poor response to
      antidepressants. These include: (1) antidepressant-induced reduction in central
      BDNF expression acutely; (2) antidepressant dose-dependent effect on central BDNF
      levels; (3) age-related effect of antidepressants on BDNF expression; (4)
      overexpression of truncated TrkB or underexpression of full-length TrkB; (5) TrkB
      pathway dysfunction and (6) antidepressant-induced mania due to increased central
      BDNF levels. Further exploration of these hypotheses would help to design
      specific treatment strategies for depressed patients who have experienced
      unfavourable responses to antidepressant treatment.

PMID- 16002235
TI  - The role of edges in the selection of a jump target in Mantis religiosa.
AB  - Before jumping to a landing object, praying mantids determine the distance, using
      information obtained from retinal image motion resulting from horizontal peering
      movements. The present study investigates the peering-jump behaviour of Mantis
      religiosa larvae with regard to jump targets differing in shape and size. The
      experimental animals were presented with square, triangular and round target
      objects with visual extensions of 20 degrees and 40 degrees. The cardboard
      objects, presented against a uniform white background, were solid black or shaded
      with a gradation from white to black. It was found that larger objects were
      preferred to smaller ones as jump targets, and that the square and triangle were
      preferred to the round disk. When two objects were presented, no preference was
      exhibited between square and triangular objects. However, when three objects were
      presented, the square was preferred. For targets with a visual angle of 40
      degrees, the amplitude and velocity of the horizontal peering movements were
      greater for the round disk than for the square or triangle. This amplification of
      the peering movements suggests that weaker motion signals are generated in the
      case of curved edges. This may help to account for the preference for the square
      and triangle as jump targets.

PMID- 16002236
TI  - Aromatic and aliphatic hydrocarbon consumption and transformation by the styrene
      degrading strain Pseudomonas putida CA-3.
AB  - Pseudomonas putida CA-3 is capable of consuming a number of aromatic and
      aliphatic hydrocarbons. With the exception of styrene none of the alkenes tested
      are capable of supporting the growth of P. putida CA-3 as sole sources of carbon
      and energy. The highest rate of alkene consumption was observed with styrene as
      the substrate. A 6.5- and 15.5-fold lower rate of substrate consumption was
      observed with indene and indole with the concomitant formation of 2-indanone and
      indigo, respectively. The presence of a sulphur (benzothiopene) or oxygen
      (benzofuran) in the cyclopentene ring resulted in further decreases in the rate
      of substrate consumption by whole cells of P. putida CA-3. P. putida CA-3 is
      incapable of consuming benzene and consumes toluene at a low rate. No detectable
      products were observed in supernatants of cultures incubated with benzothiopene,
      benzofuran or toluene. The aliphatic alkenes 1-octene and 1,7-octadiene were both
      consumed by whole cells of P. putida CA-3 at a rate equivalent to indene
      consumption. The consumption of (R) styrene oxide was 1.7- and 1.25-fold higher
      than that of the S isomer and the racemic mix, respectively. The rate of racemic
      indene oxide, 1,2-epoxyoctane and 1,2-epoxy-7-octene consumption was lower than
      their equivalent alkene and 55-, 11.8-, and 27.5-fold lower than the rate of
      racemic styrene oxide consumption. A transposon mutant incapable of growth with
      styrene or styrene oxide failed to transform indole to indigo. The ratio of
      styrene utilisation relative to other substrates changes in the mutant strain
      compared to the wild-type strain, e.g., Indene biotransformation by mutant AF5 is
      1.9-fold higher than styrene consumption compared to the wild-type strain CA-3
      where the rate of styrene consumption is 6.7-fold higher than indene consumption.
      This trend is also observed for other alkenes and epoxides.

PMID- 16002237
TI  - Sorbitol synthesis by an engineered Lactobacillus casei strain expressing a
      sorbitol-6-phosphate dehydrogenase gene within the lactose operon.
AB  - Sorbitol is claimed to have important health-promoting effects and Lactobacillus
      casei is a lactic acid bacterium relevant as probiotic and used as a cheese
      starter culture. A sorbitol-producing L. casei strain might therefore be of
      considerable interest in the food industry. A recombinant strain of L. casei was
      constructed by the integration of a d-sorbitol-6-phosphate dehydrogenase-encoding
      gene (gutF) in the chromosomal lactose operon (strain BL232). gutF expression in
      this strain followed the same regulation as that of the lac genes, that is, it
      was repressed by glucose and induced by lactose. (13)C-nuclear magnetic resonance
      analysis of supernatants of BL232 resting cells demonstrated that, when pre-grown
      on lactose, cells were able to synthesize sorbitol from glucose. Inactivation of
      the l-lactate dehydrogenase gene in BL232 led to an increase in sorbitol
      production, suggesting that the engineered route provides an alternative pathway
      for NAD(+) regeneration.

PMID- 16002238
TI  - First isolation of Streptococcus downei from human dental plaques.
AB  - In this study, we isolated four bacterial strains grown on mitis-salivarius
      sucrose bacitracin agar. The strains had similar biochemical characteristics to
      biotypes I or II of mutans streptococci. The four isolates were identified as
      Streptococcus downei by 16S rDNA and dextranase gene (dex) sequencing as well as
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      targeting dex. To our knowledge, this is the first report of the isolation and
      identification of S. downei from dental plaque in humans. The results suggest
      that S. downei can inhabit the human oral cavity.

PMID- 16002239
TI  - Cloning, sequence analysis and expression of the gene encoding a novel wide
      spectrum amidase belonging to the amidase signature superfamily from
      Achromobacter xylosoxidans.
AB  - Amidases are very important enzymes for industrial biocatalysis. We scored a
      novel amidase by screening the Achromobacter xylosoxidans gene library with
      cephalosporin analogous amides. The gene coding for the enzyme, designated ana,
      was cloned, sequenced and overexpressed in Escherichia coli. Sequence analysis of
      ana showed it to be an amidase signature family member. Interestingly, we noted
      that almost all Ana homologous amidases are from human pathogens responsible for
      chronic lung infections. Knowing the genetic context of Ana and its homologous
      amidases, we suggest that they could be a part of transposon structure. Ana can
      efficiently hydrolyze a series of cephalosporin analogous amides, including
      amides with an aninine, p-nitro-aninine, and beta-naphthylamine moiety, while
      cephalosporin could not serve as its substrate.

PMID- 16002240
TI  - Nuclear behavior in fungal hyphae.
AB  - A characteristic feature of fungal hypha is the presence of large number of
      nuclei in a common cytoplasmic environment. Where it has been examined, the
      coenocytic mycelium is commonly heterokaryotic. The nuclei cooperate, compete or
      combat. It is proposed that in addition to their classical role in heredity,
      supernumerary nuclei in filamentous fungi serve as store house for nitrogen and
      phosphorus in the form of DNA which is degraded by regulated autophagy. The
      breakdown products recycled, giving hyphal tips the capability of persistent
      extension and foraging in new areas.

PMID- 16002241
TI  - Osmotically induced trehalose and glycine betaine accumulation improves tolerance
      to desiccation, survival and efficacy of the postharvest biocontrol agent Pantoea
      agglomerans EPS125.
AB  - The application of the biocontrol agent Pantoea agglomerans EPS125 to unwounded
      fruits was practically ineffective for control of postharvest blue mould caused
      by Penicillium expansum when the treatment and subsequent wounding and pathogen
      inoculation were separated by periods of unfavourable conditions. This was due to
      a rapid decrease in viability of the alocthonous introduced biocontrol agent in
      the intact peel surface. A system for osmoadaptation of the biocontrol agent was
      developed by combining saline osmotic stress and osmolyte amendment to the growth
      medium. Osmoadapted cells accumulated trehalose and glycine betaine (GB)
      intracellularly and showed a higher tolerance to desiccation than non-osmoadapted
      cells. Osmoadaptation in NaCl plus GB during inoculum preparation increased
      considerably survival on the peel surface of apple fruits. This effect was
      significant under low relative humidity (RH) and fluctuating RH conditions, but
      was not significant at high RH. Osmoadaptation significantly improved blue mould
      control under conditions where the standard biological control treatments were
      ineffective. The rot diameter was significantly reduced in apple fruits which
      were treated with EPS125 and incubated for several days under low, high or
      fluctuating RH, followed by wounding and inoculation of P. expansum. Growth of
      EPS125 with NaCl, either with or without the addition of GB, was an effective
      osmoadaptation treatment for improving blue mould rot control. However, the
      addition of GB to the NaCl amended growth medium increased 4-5-fold growth rate
      and OD of the cultures. This is an advantage for mass production of P.
      agglomerans EPS125 in a NaCl amended growth medium.

PMID- 16002242
TI  - Debaryomyces hansenii strains with different cell sizes and surface
      physicochemical properties adhere differently to a solid agarose surface.
AB  - The initial adhesion of four Debaryomyces hansenii strains to a solid agarose
      surface was investigated and correlated with their cell size and some cell
      surface physicochemical properties, i.e. (i) hydrophobicity and (ii) electron
      donor/acceptor ability. One strain adhered very poorly, whereas the three other
      strains were more adhesive. The former strain had a very hydrophilic cell
      surface, whereas the latter strains had more hydrophobic cell surfaces. In
      addition, the strain with the lowest adhesion among the adhesive strains had a
      more hydrophobic cell surface than the two most adhesive strains. Finally, the
      more adhesive the strain was, the larger it was, and the better it was to donate
      electrons from its cell surface. These results show a clear relationship between
      the cell size, the cell surface physicochemical properties, and the initial
      adhesion of D. hansenii. A possible explanation of this relationship is
      discussed.

PMID- 16002243
TI  - Expression pattern and developmental behaviour of cellular nucleic acid-binding
      protein (CNBP) during folliculogenesis and oogenesis in fish.
AB  - In vertebrates, folliculogeneis establishes an intricate system for somatic cell
      oocyte interaction, and ultimately leads to the acquisition of their respective
      competences. Although the formation process and corresponding interactions are
      strikingly similar in diverse organisms, knowledge of genes and signaling
      pathways involved in follicle formation is very incomplete and the underlying
      molecular mechanisms remain enigmatic. CNBP has been identified for more than ten
      years, and the highest level of CNBP transcripts has been observed in adult
      zebrafish ovary, but little is known about its functional significance during
      folliculogeneis and oogenesis. In this study, we clone CNBP cDNA from gibel carp
      (Carassius auratus gibelio), and demonstrate its predominant expression in gibel
      carp ovary and testis not only by RT-PCR but also by Western blot. Its full
      length cDNA is 1402 bp, and has an ORF of 489 nt for encoding a peptide of 163
      aa. And its complete amino acid sequence shared 68.5%-96.8% identity with CNBPs
      from other vertebrates. Based on the expression characterization, we further
      analyze its expression pattern and developmental behaviour during folliculogeneis
      and oogenesis. Following these studies, we reveal an unexpected discovery that
      the CagCNBP is associated with follicular cells and oocytes, and significant
      distribution changes have occurred in degenerating and regenerating follicles.
      More interestingly, the CagCNBP is more highly expressed in some clusters of
      interconnected cells within ovarian cysts, no matter whether the cell clusters
      are formed from the original primordial germ cells or from the newly formed cells
      from follicular cells that invaded into the atretic oocytes. It is the first time
      to reveal CNBP relevance to folliculogeneis and oogenesis. Moreover, a similar
      stage-specific and cell-specific expression pattern has also been observed in the
      gibel carp testis. Therefore, further studies on CNBP expression pattern and
      developmental behaviour will be of significance for understanding functional
      roles of CNBP during gametogenesis.

PMID- 16002244
TI  - Identification and analysis of the human neural polypyrimidine tract binding
      protein (nPTB) gene promoter region.
AB  - Neural polypyrimidine tract-binding protein nPTB, originally identified as the
      neuronal counterpart of the hnRNPI/PTB protein, is an RNA binding protein
      involved into tissue-specific alternative splicing regulation. Here we describe
      the functional characterization of the promoter sequence of nPTB in HeLa and
      neuroblastoma cells. By means of genomic sequence analysis we have isolated and
      cloned a 1587-base pair region upstream the human nPTB coding region. The nPTB
      proximal promoter, although rich in G+C content and presenting putative binding
      sites for the transcription factors Sp1, NF-1, NF-kB and Oct-1, lacks a typical
      TATA box. Luciferase transient expression assays using deletion mutants have
      identified the proximal promoter region at -125 relative to the transcription
      start site. Alignment of human, murine and chimpanzee genomic sequences upstream
      the nPTB exon 1 has provided evidences for the evolutionary conservation of
      specific transcription factor binding sites.

PMID- 16002245
TI  - The influence of pellet shape, size and distribution on capsule filling--a
      preliminary evaluation of three-dimensional computer simulation using a Monte
      Carlo technique.
AB  - A computer simulation based on a Monte-Carlo technique has been developed and
      used to investigate the influence of pellet size, dispersity, shape and
      aggregation on the filling of hard shell capsules. The simulations are in general
      agreement with experimental observations previously reported. The results also
      confirm recent findings that filling is a function of pellet shape and that above
      an aspect ratio value of 1.2 filling reproducibility is reduced. The methodology
      is simple and rapid in execution allowing many computer-based experiments to be
      performed with minimum effort.

PMID- 16002246
TI  - Antispasmodic and blood pressure lowering effects of Valeriana wallichii are
      mediated through K+ channel activation.
AB  - Crude extract of Valeriana wallichii rhizome (Vw.Cr) and its fractions were
      studied for possible antispasmodic and blood pressure lowering activities to
      rationalize some of the folkloric uses. In rabbit jejunum preparations, Vw.Cr
      (0.1-3.0 mg/mL) caused relaxation of spontaneous contractions. When tested
      against high K(+) (80 mM)-induced contractions it produced weak inhibitory
      effect, while caused complete relaxation of the contractions induced by low K(+)
      (20 mM). In the presence of glibenclamide (3 microM), the inhibitory effect of
      low K(+) was shifted to the right, similar to that produced by cromakalim while,
      verapamil caused no differentiation in its inhibitory effect against low and high
      K(+)-induced contractions. In guinea pig ileum, the plant extract produced
      similar results as in rabbit jejunum. Intravenous administration of Vw.Cr,
      produced fall in arterial blood pressure in normotensive anaesthetized rats and
      this effect was partially blocked by glibenclamide. In rabbit aortic
      preparations, plant extract also caused a selective and glibenclamide-sensitive
      relaxation of low K(+) (20 mM)-induced contractions. Activity-directed
      fractionation studies revealed that the observed activity was distributed both in
      the chloroform and aqueous fractions. These results indicate that the
      antispasmodic and hypotensive effects of Valeriana wallichii are mediated
      possibly through K(ATP) channel activation, which justify its use in
      gastrointestinal and cardiovascular disorders.

PMID- 16002247
TI  - Seeking a transdisciplinary and culturally germane science: The future of
      ethnopharmacology.
AB  - Publication of the 100th issue of the Journal of Ethnopharmacology offers a
      strategic juncture to reflect on what, intellectually and practically,
      substantiates ethnopharmacology as a domain of inquiry and what its future might
      be. We characterize ethnopharmacology through the diversity of its practitioners,
      and review critiques that challenge researchers to set their sights on a theory
      driven and context-sensitive study of the pharmacologic potential of species used
      by indigenous peoples for medicine, food, and other purposes. The conclusion
      suggests themes that will inspire an integrated, transdisciplinary
      ethnopharmacology for the future.

PMID- 16002248
TI  - Traditional phytotherapy and trans-cultural pharmacy among Turkish migrants
      living in Cologne, Germany.
AB  - This article reports on an ethnopharmaceutical field study carried out among
      Turkish migrants in Cologne, western Germany, which recorded 79 botanical taxa
      and 115 plant-based preparations, encompassing 167 folk phytotherapeutical uses,
      as well as a few other biological (animal and mineral derived) remedies. One
      fourth of the recorded remedies were represented by food-medicines. Half of the
      ingredients quoted came originally from Turkey; only a few plants were gathered
      from the wild or cultivated in the Cologne area. This article discusses the
      Turkish migrants' frequent use of aerial parts of Sideritis species, the fruits
      of Pistacia terebinthus and the seeds of Peganum harmala from the perspective of
      modern phytopharmacology, phytotherapy and toxicology. It considers cultural
      adaptation related to the use of folk pharmaceuticals by analysing the
      ingredients of the Turkish folk pharmacopoeia and comparing them with those of
      the Turkish medical ethnobotany and of the phytotherapy of the host country
      (Germany). Only one third of the remedies mentioned by Turkish migrants living in
      Cologne are also known in German evidence-based phytotherapy, and less than 10%
      of the recorded phytotherapeutic uses are common to both pharmacopoeias. This
      article concludes by suggesting hypotheses on future changes affecting the
      knowledge and use of medicinal plants within the Turkish community of Cologne.

PMID- 16002249
TI  - Thai population data on 15 tetrameric STR loci-D8S1179, D21S11, D7S820, CSF1PO,
      D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and
      FGA.
AB  - The genetic variations for 15 short tandem repeat (STR) loci-D8S1179, D21S11,
      D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX,
      D18S51, D5S818 and FGA, were performed on a population of 210 unrelated Thai
      individuals using the commercially available AmpF/STR Identifiler kit.

PMID- 16002250
TI  - The evolution of DNA databases--recommendations for new European STR loci.
AB  - Following a recent meeting by the ENFSI and EDNAP groups on the 4-5 April, 2005,
      in Glasgow, UK, it was unanimously agreed that the process of standardization
      within Europe should take account of recent work that unequivocally demonstrated
      that chance of obtaining a result from a degraded sample was increased when small
      amplicons (mini-STRs) were analysed. Consequently, it was recommended that
      existing multiplexes are re-engineered to enable small amplicon detection, and
      that three new mini-STR loci with alleles <130 bp (D10S1248, D14S1434 and
      D22S1045) are adopted as universal. This will increase the number of European
      standard Interpol loci from 7 to 10.

PMID- 16002251
TI  - Diversity of NKR expression in aging T cells and in T cells of the aged: the new
      frontier into the exploration of protective immunity in the elderly.
AB  - Aging in the immune system is characterized by the contraction of the lymphocyte
      repertoire, exemplified by long-lived oligoclonal T cells that pervade the
      peripheral circulation. T-cell receptor (TCR) repertoire contraction likely
      explains the decline in immunity with chronological age as evidenced by the
      increased morbidity and mortality to common and new infections, and the low rates
      of protective responses to vaccination in the elderly. Interestingly, in vitro
      senescence models and cross sectional ex vivo studies have consistently
      demonstrated that senescent (or pre-senescent) T cells and T cells of the aged
      express unusually high densities of receptors that are normally found on natural
      killer (NK) cells, the killer cell immunoglobulin-like receptors (KIR) being the
      most diverse NK receptors (NKR). Molecular studies also show that T cells are
      programmed to express NKRs/KIRs, and T-cell clonal lineages express a variety of
      NKRs towards the end stages of their replicative lifespan. We propose that
      NKR/KIR induction in aging T cells is an adaptational diversification of the
      immune repertoire. We suggest that NKR/KIR expression in oligoclonal senescent
      and pre-senescent T cells is a compensatory adaptation to maintain immune
      competence despite the overall contraction in TCR diversity with aging. NKRs
      comprise a diverse superfamily of receptors. Mounting evidence for NKR/KIR
      signaling pathways in T cells divergent from those seen in NK cells indicate that
      senescent NKR(+)T cells are unique immune effectors. We suggest that appreciation
      of the functional diversity of these unusual NK-like T cells is central to the
      creative development of new strategies to enhance protective immunity in the
      aged.

PMID- 16002252
TI  - Food allergy and its relevance to industrial food proteins.
AB  - Food allergies can be defined as IgE-mediated hypersensitivity reactions and are
      quite distinct from food intolerances, such as Coeliac disease, with symptoms
      usually appearing within a matter of minutes of exposure. Around 1-2% of adults
      and up to 5-7% of children suffer from some type of food allergy with foods such
      as peanuts, tree nuts, wheat and soy, cow's milk, egg, fish and shellfish being
      responsible for the majority of reactions. The macromolecules recognised by IgE
      (generally proteinaceous in nature) are termed allergens. A brief description of
      the allergenic components present in the major allergenic foods is given followed
      by a short discussion regarding their importance in industrial proteins in the
      light of recent food labelling legislation for allergens.

PMID- 16002253
TI  - Ret, GFRalpha-1, GFRalpha-2 and GFRalpha-3 receptors in the human hippocampus and
      fascia dentata.
AB  - The immunohistochemical occurrence and localization of the receptor components of
      the glial cell line-derived neurotrophic factor (GDNF) family ligands, the Ret
      receptor tyrosine kinase and GDNF family receptor (GFR) alpha-1 to -3, is
      described in the human post-mortem hippocampal formation at pre- and full-term
      newborn, and adult age. Two different antibodies for each of the four-receptor
      molecules were used. Western blot analysis indicates that the availability of
      GFRalpha receptor proteins may vary with age and post-mortem delay. The
      immunohistochemical detectability of GFRalpha-1, GFRalpha-2, GFRalpha-3 and Ret
      receptor molecules is shown in the rat up to 72 h post-mortem. In the human
      specimens, labelled neuronal perikarya were detectable for each receptor protein
      at all examined ages, with prevalent localization in the pyramidal layer of the
      Ammon's horn and hilus and granular layer of the fascia dentata. In the adult
      subjects, abundant punctate-like structures were also present. Labelled glial
      elements were identifiable. Comparison of the pattern of immunoreactive elements
      among young and adult subjects suggests that the intracellular distribution of
      the GDNF family ligands may vary between pre- and perinatal life and adult age.
      The results obtained suggest the involvement of the Ret and GFRalpha receptors
      signalling in processes subserving both the organization of this cortical region
      during development and the functional activity and maintenance of the mature
      hippocampal neurons.

PMID- 16002254
TI  - NMDA receptors contribute to the survival promoting effect of high potassium in
      cultured cerebellar granule cells.
AB  - The present report further analyzes the survival promoting effect of high
      potassium, a condition that mimics neural activity in cultured cerebellar granule
      cells, an excellent model to study trophic mechanisms induced by depolarization
      and trophic factors. We found that the survival promoting effect measured at 7
      days in vitro (DIV 7) of depolarizing potassium concentrations (25 mM KCl), added
      at DIV2, is partially prevented by adding at DIV 2 the non-competitive NMDA
      blocker MK801 (10 microM). The concentration of MK801 used blocks completely the
      survival promoting effect of a supramaximal effective concentration of NMDA (100
      microM). The addition at DIV 2 of anti-brain derived neurotrophic factor (anti
      BDNF) antibody, failed to modify the effect of high potassium. The present report
      provides evidences that in cultured cerebellar granule cells, high potassium
      induced survival promoting effect is due in part by the activation of NMDA
      receptors. The effect does not require the presence of BDNF.

PMID- 16002255
TI  - Causes, characteristics and consequences of anovulatory follicles in
      superovulated sheep.
AB  - Efficiency of superovulatory protocols is affected by the occurrence of
      reproductive abnormalities, such as the presence of anovulatory follicles. The
      objective of current study was to assess the incidence and possible causes of
      anovulatory follicles in superovulated sheep, in order to characterize the
      endocrine functionality of these follicles in terms of estradiol production and
      to evaluate their relationship with development of embryos from other follicles.
      The number and size of all follicles present in the ovaries of 12 sheep treated
      with a superovulatory FSH step-down treatment was assessed by ultrasonography. On
      Day 3 after subsequent estrus behaviour, the number of corpora lutea and
      anovulatory follicles were recorded and the fluid of anovulatory follicles
      >or=5mm in size was aspirated and assayed for estradiol. At once, embryos were
      recovered to evaluate their viability. In current study, anovulatory structures
      averaged 34.6% of the follicles developing to preovulatory sizes. The number of
      anovulatory follicles was determined by the existence of follicular dominance
      effects, since they increased with a higher difference in size between the
      largest and the second largest follicle at the beginning of the superovulatory
      treatment (P<0.05, r(2)=0.420). Most of the anovulatory follicles showed signs of
      functionality failures, indicated by a low mean estradiol concentration (9.9+/
      1.1 ng/ml). However, a 22.4% of them were highly estrogenic (>200 ng/ml) and
      their permanence beyond the ovulation was related to a drop in the embryo
      viability rate (P<0.005), leading to decreased final superovulatory yields.

PMID- 16002256
TI  - Propionate is not an important regulator of plasma leptin concentration in dairy
      cattle.
AB  - Propionate was recently shown to increase leptin synthesis in rodents. To
      determine if a similar effect occurs in ruminants, propionate was administered to
      lactating dairy cows. In experiment 1, 31 cows were given an intrajugular Na
      propionate bolus (1,040 micromol/kg body weight), increasing plasma propionate
      from 160 to 5,680 microM and plasma insulin from 6.8 to 77.8 microIU/mL. Plasma
      leptin concentration decreased from 2.11 ng/mL before bolus to 1.99 ng/mL after
      dosing (P<0.05) with no differences in leptin concentrations at 20, 50, and 100
      min post-bolus (P>0.10). In experiment 2, 12 cows were used in a duplicated 6 x 6
      Latin square experiment to assess the dose-response effect of ruminal propionate
      infusion on plasma leptin concentration. Sodium propionate was infused at rates
      of 0, 260, 520, 780, 1040, or 1,300 mmol/h, while total short-chain fatty acid
      infusion rate was held constant at 1,300 mmol/h by addition of Na acetate to the
      infusate. Coccygeal blood was sampled following 18 h of infusion. Increasing the
      rate of propionate infusion linearly increased plasma propionate concentration
      from 180 to 330 microM (P<0.001) and plasma insulin concentration from 6.7 to 9.1
      microIU/mL (P<0.05). There was a quadratic response in plasma leptin
      concentration (P=0.04) with a maximum at 780 mmol/h propionate, but leptin
      concentrations increased by no more than 8% relative to the 0 mmol/h propionate
      infusion. Leptin concentrations were correlated with insulin concentrations but
      not with propionate concentrations in plasma. Propionate is not a physiological
      regulator of leptin secretion in lactating dairy cows.

PMID- 16002257
TI  - Microvascular radial forearm fasciocutaneous free flap in hard palate
      reconstruction.
AB  - THE AIM OF THIS STUDY: To report the reconstruction of palatal defects by
      microvascular radial forearm fasciocutaneous free flap (RFFF) and to report
      patient's quality of life outcomes after this procedure. MATERIAL AND METHODS:
      During the period 1990-2002, 30 cases of palatal defects were reconstructed using
      RFFF in our institution. RFFF allowed restoration of a vestibular sulcus to
      maintain dental prostheses. Outcome measurements included post-operative
      assessment of speech, swallowing and diet evaluation 6 months, 1 year and 2 years
      after reconstruction. Quality of life outcomes were measured 1 and 2 years post
      reconstruction. RESULTS: RFFF surgery was successful in 28 cases. Six months
      after resection 28 patients reported satisfactory speech and swallowing. Two
      years after surgery, 92% (n=26) of patients resumed a normal diet. All patients
      underwent dental evaluation and 68% (n=19) of patients required dental
      rehabilitation over a post-operative period of 3-18 months. Patients self
      assessed their quality of life on a scale of 0-2. First year post-operatively, 21
      patients reported a good quality of life (score=2). After the second year, 26
      patients reported a good quality of life and the remaining two patients reported
      an intermediate quality of life (score=1) because they did not resume a normal
      diet. CONCLUSION: RFFF for palatal reconstruction is a reliable technique and
      provides a definitive separation between oral and sinusonasal cavities.
      Furthermore, it improves quality of life by improving speech, swallowing and
      chewing. It should be considered an integral component of head and neck cancer
      therapy and rehabilitation.

PMID- 16002258
TI  - Vector-primed mice display hypo-responsiveness to foreign antigen presented by
      recombinant Salmonella regardless of the route of delivery.
AB  - Our previous studies have shown that mice which have been orally primed with an
      attenuated Salmonella vector [S. enterica serovar Stanley] are hypo-responsive to
      foreign antigens later delivered orally by the same vector strain, responding
      with significantly impaired serum and intestinal antibody responses compared with
      those seen in unprimed controls. Initial vector priming of the gut-associated
      lymphoid tissue (GALT) is likely to result in impaired persistence of recombinant
      Salmonella later administered orally. Delivery of recombinant bacteria by the
      intra-peritoneal or intra-nasal route, to avoid exposure to a primed GALT, did
      not allow vector-primed recipients to mount normal antibody responses to the
      foreign pilus protein K88. The negative impact of vector priming could be largely
      overcome, however, if mice were exposed to the foreign protein just prior to
      priming with the vector strain. Using this strategy, vector-primed mice displayed
      normal gut IgA and intermediate serum IgG responses to K88 following oral
      administration of recombinant Salmonella. Our findings are compatible with the
      concept of epitopic suppression, in which failure to respond to the foreign
      vaccine antigen reflects the clonal dominance of B cells specific for epitopes
      associated with the vector strain.

PMID- 16002259
TI  - A mutation in the 65,000 Dalton heat shock protein gene, commonly used for
      molecular identification of non-tuberculous mycobacteria, leads to the
      misidentification of Mycobacterium malmoense as Mycobacterium marinum.
AB  - We describe a case of a Mycobacterium isolated from a patient with cervical
      lymphadenitis which was initially identified by hsp65 RFLP as Mycobacterium
      marinum. Sequence analysis of the hsp65 DNA fragment and the 16S rDNA signature
      sequence, however, led to the identification of Mycobacterium malmoense. A point
      mutation in one of the restriction sites had shifted the M. malmoense typical
      RFLP pattern to the M. marinum specific RFLP pattern. As a consequence, care
      should be taken when identifying mycobacteria with the use of one molecular
      technique, only.

PMID- 16002260
TI  - Neuropil reactivity, distribution and morphology of NADPH diaphorase type I
      neurons in the barrel cortex of the adult mouse.
AB  - The mouse, like a few other rodent and marsupial species, displays a striking
      modular architecture in its primary somatosensory cortex (SI). These modules,
      known as barrels, are mostly defined by the peculiar arrangement of granule cells
      and thalamic axons in layer IV. In the present work, we studied both the
      distribution and morphology of neurons stained for NADPH diaphorase (NADPH-d) and
      neuropil reactivity in the posteromedial barrel subfield (PMBSF), which
      represents the mystacial whiskers. We then compared our results with previous
      descriptions of NADPH-d distribution in both neonatal and young mice. We found
      two types of neurons in the PMBSF: type I neurons, which have large cell bodies
      and are heavily stained by the NADPH-d reaction; and type II neurons,
      characterized by relatively small and poorly stained cell bodies. The
      distribution of type I cells in the PMBSF was not homogenous, with cells tending
      to concentrate in septa between barrels. Moreover, the cells found in septal
      region possess both a larger and more complex dendritic arborization than cells
      located inside barrels. Our findings are at variance with results from other
      groups that reported both an absence of type II cells and a homogeneous
      distribution of type I cells in the PMBSF of young animals. In addition, our
      results show a distribution of type I cells which is very similar to that
      previously described for the rat's barrel field.

PMID- 16002261
TI  - Neurochemical correlates of autistic disorder: a review of the literature.
AB  - Review of neurochemical investigations in autistic disorder revealed that a wide
      array of transmitter systems have been studied, including serotonin, dopamine,
      norepinephrine, acetylcholine, oxytocin, endogenous opioids, cortisol, glutamate,
      and gamma-aminobutyric acid (GABA). These studies have been complicated by the
      fact that autism is a very heterogeneous disorder which often presents with
      comorbid behavioral problems. In addition, many of these studies employed very
      small samples and inappropriate control groups, making it difficult to draw
      conclusions with confidence. Overall, serotonin appears to have the most
      empirical evidence for a role in autism, but this requires further investigation
      and replication. There is little support for the notion that a dysfunction of
      norepinephrine or the endogenous opioids are related to autism. The role of
      dopaminergic functioning has not been compelling thus far, though conflicting
      findings on central dopamine turnover require further study. Promising new areas
      of study may include possible dysfunction of the cholinergic system, oxytocin,
      and amino acid neurotransmitters. Implications for pharmacotherapy are briefly
      discussed for each neurotransmitter system with brief research examples. Review
      of this work emphasizes the need for future studies to control for subject
      variables, such as race, sex, pubertal status, and distress associated with blood
      draws, which can affect measures of neurochemical function. In addition, research
      in neurochemistry must continue to work in concert with other subspecialties to
      form a more comprehensive and theory-based approach to the neurobiological
      correlates of autistic disorder.

PMID- 16002262
TI  - On the importance of test validity and the experimental doubt.

PMID- 16002263
TI  - Image segmentation feature selection and pattern classification for mammographic
      microcalcifications.
AB  - Since microcalcifications in X-ray mammograms are the primary indicator of breast
      cancer, detection of microcalcifications is central to the development of an
      effective diagnostic system. This paper proposes a two-stage detection procedure.
      In the first stage, a data driven, closed form mathematical model is used to
      calculate the location and shape of suspected microcalcifications. When tested on
      the Nijmegen University Hospital (Netherlands) database, data analysis shows that
      the proposed model can effectively detect the occurrence of microcalcifications.
      The proposed mathematical model not only eliminates the need for system training,
      but also provides information on the borders of suspected microcalcifications for
      further feature extraction. In the second stage, 61 features are extracted for
      each suspected microcalcification, representing texture, the spatial domain and
      the spectral domain. From these features, a sequential forward search (SFS)
      algorithm selects the classification input vector, which consists of features
      sensitive only to microcalcifications. Two types of classifiers-a general
      regression neural network (GRNN) and a support vector machine (SVM)--are applied,
      and their classification performance is compared using the Az value of the
      Receiver Operating Characteristic curve. For all 61 features used as input
      vectors, the test data set yielded Az values of 97.01% for the SVM and 96.00% for
      the GRNN. With input features selected by SFS, the corresponding Az values were
      98.00% for the SVM and 97.80% for the GRNN. The SVM outperformed the GRNN,
      whether or not the input vectors first underwent SFS feature selection. In both
      cases, feature selection dramatically reduced the dimension of the input vectors
      (82% for the SVM and 59% for the GRNN). Moreover, SFS feature selection improved
      the classification performance, increasing the Az value from 97.01 to 98.00% for
      the SVM and from 96.00 to 97.80% for the GRNN.

PMID- 16002264
TI  - Role of c-KIT expression level and phosphatidylinositol 3-kinase activation in
      survival and proliferative responses of early myeloid cells.
AB  - The receptor tyrosine kinase c-KIT and its ligand Stem Cell Factor (SCF) are
      critical in haemopoiesis but pathways linking receptor activation to specific
      responses in progenitor cells are still unclear. We have investigated the role of
      c-KIT expression level and the phosphatidylinositol 3-kinase (PI3-K) pathway in
      survival and cell division of early myeloid cells in response to SCF. Two factor
      dependent murine early myeloid cell lines, FDC-P1 and Myb-immortalised
      haemopoietic cells (MIHC), were transduced to express wild-type c-KIT or a mutant
      form of the receptor (Y721F) that lacks the major recruitment site for the p85
      regulatory subunit of PI3-K. Several clones expressing different receptor levels
      were analysed in each case. Growth of cells expressing either the wild-type or
      Y721F mutant KIT was strongly dependent on receptor level within the
      physiological range. Using an assay that allows quantitative measurement of the
      contributions of cell survival and cell division, diminished cell growth in
      response to SCF under limiting conditions of receptor copy number or PI3-K
      recruitment was shown to be almost entirely due to decreased cell survival.
      Further studies with the PI3-K inhibitor LY294002 indicated that PI3-K activation
      was also required for cell division. Alternate binding and/or indirect activation
      of PI3-K could support cell division mediated by Y721F mutant KIT, but was
      insufficient for the survival response.

PMID- 16002265
TI  - Contributions of subtype and spectral frequency analyses to the study of P50 ERP
      amplitude and suppression in schizophrenia.
AB  - BACKGROUND: Poor suppression of P50 event-related potential (ERP) amplitudes to
      paired-click stimuli may indicate genetic liability for schizophrenia and weak
      "sensory gating." Evidence suggests, however, that P50 amplitude is selectively
      impaired in nonparanoid, but not paranoid, schizophrenia subtypes. Furthermore,
      paired-click suppression can appear deficient in schizophrenia due to smaller
      evoked responses to the first stimulus (S1), rather than larger, less effectively
      "gated" responses to the second (S2). Finally, the P50 ERP is comprised of
      activity from at least two frequency components that may be distinctly impaired:
      the gamma band, associated with sensory registration, and the low frequency
      response, associated with attention/encoding processes. P50 and related frequency
      subcomponents were examined as a function of illness subtype to further integrate
      these concepts. METHOD: The standard paired-click paradigm was administered to 38
      schizophrenia (27 paranoid, 11 nonparanoid) and 38 age-matched healthy control
      participants. P50 amplitudes and spectral power of gamma band (GBR; 20-50 Hz) and
      low frequency (LFR; 1-20 Hz) responses were analyzed. RESULTS: P50 analyses
      revealed smaller S1 amplitude and normal S2 in schizophrenia participants
      collectively, but no differentiation of schizophrenia subtypes. Spectral analyses
      revealed smaller magnitude S1 and normal S2 responses in schizophrenia across
      both the GBR and LFR. The LFR, but not GBR, was found to distinguish nonparanoid
      from control groups, while paranoid participants evidenced no impairment in
      either frequency domain. LFR amplitude values correlated with clinical ratings of
      cognitive symptomatology. CONCLUSIONS: ERP deficits in the dual-click paradigm
      were specific to S1 amplitudes and most prominent in the low frequency response.
      These results replicate previous findings and extend their relevance to
      schizophrenia subtype distinctions. Implications for the recurrent inhibition
      model of sensory gating are discussed.

PMID- 16002266
TI  - Organization of semantic category exemplars in schizophrenia.
AB  - Semantic memory was investigated in 27 individuals with schizophrenia and 30
      healthy controls using an animal similarity judgment and organization test with
      reduced retrieval demands. Participants arranged 12 common animal names according
      to similarity on a computer screen and provided verbal descriptions of
      organizational strategies. Distance between each animal pair was compared to the
      number of shared semantic attributes between the pairs (e.g., size, diet,
      habitat). The three primary organizational strategies included single animals not
      related to other exemplars, isolated clusters of animals that shared a single
      strategic relationship (e.g., pets), and overlapping clusters that combined more
      than one strategic relationship (e.g., cats and mammals). A strong negative
      correlation was observed between distance ratings and number of shared semantic
      attributes, confirming that semantic features related to visual distances in both
      groups. Animal pairs that shared few semantic attributes were placed in closer
      proximity in the schizophrenia group, whereas the groups placed animal pairs
      sharing more features equidistantly. Analyses of clustering strategies revealed a
      double dissociation, with patients relying on isolated, non-overlapping clusters
      and controls producing more overlapping semantic clusters. Results suggest that
      performance differences on semantic tasks with limited retrieval demands in
      schizophrenia relate to difficulties utilizing higher-order categorization
      strategies.

PMID- 16002267
TI  - Constitutive expression of bvgR-repressed factors is not detrimental to the
      Bordetella bronchiseptica-host interaction.
AB  - Bordetella bronchiseptica infection requires the activation of virulence genes by
      the two-component BvgAS regulatory system, which also activates bvgR, a repressor
      of another set of genes called avirulence genes. Whether or not BvgR-repressed
      genes play a role in pathogenesis is poorly understood. To evaluate their
      possible contribution to the bacteria-host interaction we constructed a B.
      bronchiseptica bvgR insertional mutant (BbBvgR mutant). As expected, this mutant
      simultaneously expressed virulence and avirulence markers. In vitro experiments
      demonstrated that, although the BbBvgR mutant expressed avirulence factors during
      its virulent state, the bacteria adhered to and survived within human epithelial
      cells as efficiently as the wild-type strain. The mutant was not impaired for
      colonization of the respiratory tract in vivo, as it was effectively cleared from
      lungs during the same time period as the wild-type strain.

PMID- 16002268
TI  - Stress stimulus induced resistance to Cladosporium cucumerinum in cucumber
      seeding.
AB  - Up to date, the studies of plant induced resistance have become the focus in
      plant pathology and physiology. During the course of pathogens penetrating the
      plant cell, besides of chemical secretion, the pathogens may generate mechanical
      signal caused by the physical pressure on the plant cell. In the non-host
      resistance, both the chemical signal and the mechanical stress signal are
      considered to have contribution to the entire defense reaction acted by the
      plant. The penetration of pathogen Cladosporium cucumerinum to cucumber is
      thought to be one of the model in research of plant induced resistance. In the
      current study, as a mechanical signal elicitor, the appropriate stress stimulus
      was proved to effectually induce the resistance of cucumber seedling to C.
      cucumerinum. After the treatment of the stress stimulus on leaves, the activities
      of resistance-related enzymes were significantly increased, such as phenylanine
      ammonia lyase (PAL), peroxidase (POD). Also, we found that stress stimulation may
      cause synthesis of lignin, which acts as the physical barrier to defense the
      pathogens. The results suggest that stress stimulation may not only enhance
      ability of the plant cell resistance to pathogen penetration but also elicit the
      accumulation of pathogens suppression or antimicrobial chemical substance in the
      plant cell.

PMID- 16002269
TI  - CpG oligonucleotides partially inhibit growth of Mycobacterium tuberculosis, but
      not Salmonella or Listeria, in human monocyte-derived macrophages.
AB  - Immunostimulatory DNA sequences and their synthetic oligonucleotide analogs (CpG
      ODN) activate innate immunity and can stimulate antibacterial effects against
      numerous intracellular pathogens. While it has been shown previously that CpG-ODN
      inhibit growth of Mycobacterium avium in murine and human macrophages, we now
      report that Mycobacterium tuberculosis growth can be inhibited by CpG-ODN
      treatment of human monocyte-derived macrophages (hMDM). This inhibitory effect
      was reversed by IFN-gamma, which has been shown repeatedly to enhance the growth
      of virulent M. tuberculosis in cultured hMDM. The antibacterial effect of CpG-ODN
      in human macrophages was specific for M. tuberculosis when compared to other
      intracellular pathogens including Listeria monocytogenes and Salmonella enterica
      serovar Dublin. These data indicate that CpG-ODN can improve the ability of hMDM
      to contain growth of virulent M. tuberculosis.

PMID- 16002270
TI  - IL-8 and airway neutrophilia in children with gastroesophageal reflux and asthma
      like symptoms.
AB  - Gastroesophageal reflux (GER) may induce respiratory symptoms (RS) through
      inhalation of acid gastric contents. To characterize the airway inflammation
      associated with this condition, 20 children [7.4 (0.9) yr old] with "difficult to
      treat" RS and a positive 24-h oesophageal pH monitoring (pHm) were studied and
      bronchoalveolar lavage (BAL) performed. The control group included 10 children
      [7.3 (1.3) yr], non-atopics, with a respiratory clinical history similar to the
      cases but no reflux, as demonstrated by a negative 24-h oesophageal pHm. On BAL
      samples, in addition to inflammatory indexes, the lipid-laden macrophage (LLM)
      index was determined as index of gastric content inhalation. As compared to
      controls, GER children had higher neutrophil proportion (P=0.002), higher LLM
      index (P=0.004) and higher concentrations of interleukin (IL)-8 (P=0.005),
      myeloperoxidase (MPO) (P=0.001) and elastase (P=0.045) in BAL fluid. In GER
      children, but not in controls, neutrophil proportion significantly correlated
      with LLM index (r=0.65, P=0.002), with IL-8 (r=0.62, P=0.003) and MPO levels
      (r=0.54, P=0.014) but not with elastase concentrations. These results suggest an
      active pathogenetic role of IL-8 in the recruitment and activation of neutrophils
      in the airways of children with GER, respiratory symptoms and BAL findings
      suggestive of gastric content aspiration.

PMID- 16002271
TI  - Survival in idiopathic pulmonary fibrosis-cytotoxic agents compared to
      corticosteroids.
AB  - STUDY OBJECTIVE: To compare the survival of patients with IPF treated
      retrospectively with corticosteroids alone, to survival of patients treated with
      immunosuppressive and corticosteroids combined. DESIGN: Non-randomized
      retrospective cohort study. SETTING: Three tertiary centers in Brazil. PATIENTS:
      Eighty-two IPF patients were included. The diagnosis was confirmed by open lung
      biopsy in 48. Patients received either corticosteroids alone (group I) or
      cytotoxic agents in addition to corticosteroids (group II). MEASUREMENTS AND
      RESULTS: The primary end-point was mortality. Secondary outcome included
      longitudinal changes in FVC. Mean age was 66+/-8 years. FVC was 71+/-17% of
      predicted. There were 48 deaths during the study period (59%), 44 secondary to
      respiratory causes. From preliminary univariate analysis, for the group as a
      whole, worse survival was found to be associated with FVC% <70% of predicted
      (P=0.004), evidence of disease progression by follow-up FVC measurements
      (P=0.01), and pharmacologic treatment (P=0.014). Median survival was 25 months
      for the group I, and 45 months for the group II (Log-Rank=6.45, P=0.01). After
      adjusting for FVC > or =70% and<70% of predicted, there was evidence to indicate
      that survival was associated with recommended pharmacologic treatment only in
      patients with FVC> or =70% (Log Rank=6.84, P=0.009). CONCLUSIONS: The combination
      of immunosuppressive agents and prednisone results in better survival when
      compared to prednisone alone in patients with IPF. The benefit seems to occur
      only in patients with less severe disease, as reflected by FVC> or =70%.

PMID- 16002272
TI  - Application of laser spectroscopy for measurement of exhaled ethane in patients
      with lung cancer.
AB  - There is increasing interest in ethane (C(2)H(6)) in exhaled breath as a non
      invasive marker of oxidative stress (OS) and thereby a potential indicator of
      disease. However, the lack of real-time measurement techniques has limited
      progress in the field. Here we report on a novel Tunable Diode Laser Spectrometer
      (TDLS) applied to the analysis of exhaled ethane in patients with lung cancer.
      The patient group (n=52) comprised randomly selected patients presenting at a
      respiratory clinic. Of these, a sub-group (n=12) was subsequently diagnosed with
      lung cancer. An age-matched group (n=12) corresponding to the lung cancer group
      was taken from a larger control group of healthy adults (n=58). The concentration
      of ethane in a single exhaled breath sample collected from all subjects was later
      measured using the TDLS. This technique is capable of real-time analysis of
      samples with accuracy 0.1 parts per billion (ppb), over 10 times less than
      typical ambient levels in the northern hemisphere. After correcting for ambient
      background, ethane in the control group (26% smokers) ranged from 0 to 10.54 ppb
      (median of 1.9 ppb) while ethane in the lung cancer patients (42% smokers) ranged
      from 0 to 7.6 ppb (median of 0.7 ppb). Ethane among the non-lung cancer patients
      presenting for investigation of respiratory disease ranged from 0 to 25 ppb
      (median 1.45 ppb). We conclude that, while the TDLS proved effective for accurate
      and rapid sample analysis, there was no significant difference in exhaled ethane
      among any of the subject groups. Comments are made on the suitability of the
      technique for monitoring applications.

PMID- 16002273
TI  - Influence of tropical seasonal variations on landfill leachate characteristics-
      results from lysimeter studies.
AB  - Considering the quality of design and construction of landfills in developing
      countries, little information can be derived from randomly taken leachate
      samples. Leachate generation and composition under monsoon conditions have been
      studied using lysimeters to simulate sanitary landfills and open cell settings.
      In this study, lysimeters were filled with domestic waste, highly organic market
      waste and pre-treated waste. Results over two subsequent dry and rainy seasons
      indicate that the open cell lysimeter simulation showed the highest leachate
      generation throughout the rainy season, with leachate flow in all lysimeters
      coming to a halt during the dry periods. More than 60% of the precipitation was
      found in the form of leachate. The specific COD and TKN load discharged from the
      open cell was 20% and 180% more than that of the sanitary landfill lysimeters.
      Types of waste material and kind of pre-treatment prior to landfilling strongly
      influenced the pollutant load. Compared to the sanitary landfill lysimeter filled
      with domestic waste, the specific COD and TKN load discharged from the pre
      treated waste lysimeter accounted for only 4% and 16%, respectively. Considering
      the local settings of tropical landfills, these results suggest that landfill
      design and operation has to be adjusted. Leachate can be collected and stored
      during the rainy season, and recirculation of leachate is recommended to maintain
      a steady and even accelerated degradation during the prolonged dry season. The
      open cell approach in combination with leachate recirculation is suggested as an
      option for interim landfill operations.

PMID- 16002275
TI  - Investigations of the antioxidant properties of plant extracts using a DNA
      electrochemical biosensor.
AB  - In this work, the results of a method based on an electrochemical biosensor to
      detect DNA damage in vitro for the evaluation of the antioxidant properties of
      plant extracts are reported. The biosensor consisted of a dsDNA immobilized on a
      screen-printed electrode surface (SPE). DNA damage was promoted by the generation
      of the *OH radicals via Fenton-type reaction. The interaction of the radical
      species with immobilised DNA in the absence and presence of antioxidants was
      evaluated by means of changes in the guanine oxidation peak obtained by square
      wave voltammetry. The results demonstrated that the DNA-based biosensor is
      suitable as a rapid screening test for the evaluation of antioxidant properties
      of samples.

PMID- 16002276
TI  - DNA and protein microarray printing on silicon nitride waveguide surfaces.
AB  - Sputtered silicon nitride optical waveguide surfaces were silanized and modified
      with a hetero-bifunctional crosslinker to facilitate thiol-reactive
      immobilization of contact-printed DNA probe oligonucleotides, streptavidin and
      murine anti-human interleukin-1 beta capture agents in microarray formats. X-ray
      photoelectron spectroscopy (XPS) was used to characterize each reaction sequence
      on the native silicon oxynitride surface. Thiol-terminated DNA probe
      oligonucleotides exhibited substantially higher surface printing immobilization
      and target hybridization efficiencies than non-thiolated DNA probe
      oligonucleotides: strong fluorescence signals from target DNA hybridization
      supported successful DNA oligonucleotide probe microarray fabrication and
      specific capture bioactivity. Analogously printed arrays of thiolated
      streptavidin and non-thiolated streptavidin did not exhibit noticeable
      differences in either surface immobilization or analyte capture assay signals.
      Non-thiolated anti-human interleukin-1 beta printed on modified silicon nitride
      surfaces reactive to thiol chemistry exhibited comparable performance for
      capturing human interleukin-1 beta analyte to commercial amine-reactive
      microarraying polymer surfaces in sandwich immunoassays, indicating substantial
      non-specific antibody-surface capture responsible for analyte capture signal.

PMID- 16002277
TI  - Inspired by nature: an exploration of biocatalyzed siloxane bond formation and
      cleavage.
AB  - The intricate siliceous architectures of diatom species have inspired our
      exploration of biosilicification. In vitro studies of natural systems within the
      area of silica biosynthesis are complicated. Previous studies, which included
      biomimetic approaches, often failed to recognize the chemistry of silicic acid
      and its analogues. To better understand the role of various proteins in the
      biosilicification process, recent studies have been conducted to test the ability
      of enzymes to catalyze the formation and cleavage of siloxane bonds. Notably,
      biocatalysis at silicon was observed. Further understanding of the
      biotransformation strategy in the design and synthesis of structurally complex
      materials would be beneficial.

PMID- 16002278
TI  - Cyclooxygenase-2: how good is it as a target for cancer chemoprevention?
AB  - There is now substantial evidence for a role for cyclooxygenase-2 (COX-2)
      mediated prostaglandin (PG) signalling during carcinogenesis in a number of
      tissues and selective COX-2 inhibitors (coxibs) were considered attractive
      candidate chemoprevention agents. However, recent concerns over the toxicity of
      systemic selective COX-2 inhibition and the realisation that COX-1 may also
      contribute to carcinogenesis have cast some doubt on COX-2 inhibition as a safe
      and effective chemoprevention strategy. This review will describe the available
      evidence relating to the known benefits (preventive efficacy in rodent
      tumorigenesis models and limited human data from small randomised, controlled
      trials and epidemiological studies) and risks (cardiovascular and renal toxicity)
      of coxib therapy for cancer chemoprevention. Potential, alternative strategies
      for inhibition of COX-PG signalling that minimise or avoid systemic selective COX
      2 inhibition will also be discussed.

PMID- 16002280
TI  - Aromatase inhibitors: cellular and molecular effects.
AB  - Marked cellular and molecular changes may occur in breast cancers following
      treatment of postmenopausal breast cancer patients with aromatase inhibitors.
      Neoadjuvant protocols, in which treatment is given with the primary tumour still
      within the breast, are particularly illuminating. In Edinburgh, we have shown
      that 3 months treatment with either anastrozole, exemestane or letrozole produces
      pathological responses in the majority of oestrogen receptor (ER)-rich tumours
      (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in
      histological grading may also take place, most notably a reduction in mitotic
      figures. This probably reflects an influence on proliferation as most tumours
      (82%) show a marked decrease in the proliferation marker, Ki67. These effects are
      generally more dramatic than seen with tamoxifen given in the same setting.
      Differences between aromatase inhibitors and tamoxifen are also apparent in
      changes in steroid hormone expression. Thus, immuno-staining for progesterone
      receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming
      undetectable in many. This contrasts with effects of tamoxifen in which the most
      common change on PgR is to increase expression. Changes in proliferation occur
      rapidly following the onset of exposure to aromatase inhibitors. Thus,
      neoadjuvant studies with letrozole in which tumour was sampled before and after
      14 days and 3 months treatment show that decreased expression of Ki67 occur at 14
      days and, in many cases, the effect is greater at 14 days than 3 months. These
      early changes precede evidence of clinical response but do not predict for it.
      However, this study design has allowed RNA analysis of sequential biopsies taken
      during the neoadjuvant therapy. Based on clustering techniques, it has been
      possible to subdivide tumours into groups showing distinct patterns of molecular
      changes. These changes in tumour gene expression may allow definition of tumour
      cohorts with differing sensitivity to aromatase inhibitors and permit early
      recognition of response and resistance.

PMID- 16002281
TI  - Clinical use of aromatase inhibitors (AI) in premenopausal women.
AB  - Aromatase inhibitors (AI) block the last enzymatic step of estrogen production,
      the aromatization of the A-cycle of aromatizable androgens and particularly,
      androstenedione (delta4) and testosterone (T). Molecules designed for interfering
      with aromatase activity have existed for many years. Yet the activity of products
      of the aminogluthetimide era was unspecific and these substances carried too many
      side effects for being used clinically. Newer third generation AIs, however, are
      highly specific and essentially devoid of side effects. These molecules have
      recently been approved for treating breast cancer in postmenopausal women either,
      in advanced forms or, as part of adjuvant therapy. In women whose ovaries are
      active, a temporary inhibition of E2 production will raise gonadotropins and in
      turn, stimulate follicular growth. In cancer patients, this property precludes
      the use of AIs in women whose ovaries are still active, unless gonadotropins are
      blocked. But in infertility patients, this property of AIs has been put to play
      for inducing ovulation. AIs have been used both in women who do not ovulate but
      whose hypothalamo-pituitary-gonadal (HPG) axis is active (oligo-anovulators of
      PCOD type) and those who ovulate regularly but in whom multiple ovulation is
      sought for treating unexplained infertility or as part of IVF. Like clomiphene
      citrate (CC), AIs are not usable in women whose gonadotropins are suppressed, as
      in the case of hypothalamic amenorrhea. The sum of data available on the use of
      AI for inducing ovulation remains however meager to this date and is mainly
      constituted of pilot and non-randomized trials. Yet mounting evidence tends to
      support AIs' advantages over CC for induction of ovulation. Hence, we think that
      the likelihood that these drugs will play a key role in induction of ovulation in
      the future is high. AIs appear particularly interesting for treating unexplained
      infertility because AI-FSH/hMG regimens are lighter than FSH-only regimens while
      retaining the high pregnancy rates of these latter treatments.

PMID- 16002282
TI  - New alpha-methylene-gamma-butyrolactones with antimycobacterial properties.
AB  - The synthesis and antimycobacterial activity of a series of alpha-methylene-gamma
      butyrolactones based on the natural product protolichesterinic acid are
      described. Compounds 9-12 bearing an allylamide group at the C-4 position showed
      improved activity with MICs in the range of 6.25-12.5 microg/mL.

PMID- 16002283
TI  - New HIV-1 replication inhibitors of the styryquinoline class bearing aroyl/acyl
      groups at the C-7 position: synthesis and biological activity.
AB  - Novel variants of HIV-1 replication inhibitors of the styrylquinoline class
      harboring aroyl/acyl group at the C-7 position have been synthesized. In sharp
      contrast with styrylquinolines bearing a carboxylic acid group at C-7, these
      compounds proved to be inactive toward HIV-1 integrase in in vitro assays.

PMID- 16002284
TI  - Trichloroacetaldehyde modified oligonucleotides.
AB  - Some commercial batches of dichloroacetic acid (DCA) contain traces of chloral
      (trichloroacetaldehyde). Using such DCA to effect detritylation during solid
      phase oligonucleotide synthesis results in the formation of a family of process
      impurities in which the atoms of chloral (Cl3CCHO) are incorporated between the
      5'-oxygen and phosphorus atoms of an internucleotide linkage. The structure was
      elucidated by HPLC with UV and MS detection, digestion of the oligonucleotide,
      synthesis of model compounds, and 1H and 31P NMR spectroscopy. By understanding
      the chemistry behind its formation, we are now able to limit levels of this
      impurity in synthetic oligonucleotides by limiting chloral in DCA.

PMID- 16002285
TI  - Synthesis and antiamoebic activity of new oxime ether derivatives containing 2
      acetylpyridine/2-acetylfuran.
AB  - Various oxime ether derivatives of 2-acetylpyridine and 2-acetylfuran series have
      been synthesised. O-Alkylation of the oximes by various alkylaminoethyl halides
      gave the corresponding oxime ether derivatives. The structures of these compounds
      were elucidated by UV, IR, 1H NMR, 13C NMR spectroscopic methods and elemental
      analyses. All the compounds were screened in vitro against the HM1:IMSS strain of
      Entamoeba histolytica. Based on the 50% inhibitory concentration (IC50) data of
      the 12 compounds evaluated, two of the 2-acetylpyridine series and two in the 2
      acetylfuran series showed better IC50 values in vitro when compared with the
      standard amoebicidal drug, metronidazole. Moreover, one compound showed the most
      promising antiamoebic activity (IC50=0.5 microM vs IC50=1.9 microM of
      metronidazole).

PMID- 16002286
TI  - Utilizing the intramolecular Fukuyama-Mitsunobu reaction for a flexible synthesis
      of novel heterocyclic scaffolds for peptidomimetic drug design.
AB  - We report the synthesis of the novel scaffolds pyrazino[1,2-b]isoquinoline and
      pyrrolo[1,2-a]pyrazine displaying the somatostatin pharmacophores. Both classes
      of compounds contain a pyrazine heterocycle, which can be prepared in a
      straightforward manner utilizing an intramolecular Fukuyama-Mitsunobu reaction.
      As both the families derive from amino acids, they can be accessed in high
      optical purity.

PMID- 16002287
TI  - Phenylpyrroles, a new chemolibrary virtual screening class of 5-HT7 receptor
      ligands.
AB  - Virtual screening studies have identified a series of phenylpyrroles as novel 5
      HT7 receptor ligands. The synthesis and the affinity for the 5-HT7 receptor of
      these phenylpyrroles are described. Some of these compounds exhibited high
      affinity for the 5-HT7 receptors.

PMID- 16002288
TI  - Structure-activity relationship studies of salubrinal lead to its active
      biotinylated derivative.
AB  - The synthesis and structure-activity relationships (SAR) of salubrinal, a small
      molecule that protects cells from apoptosis induced by endoplasmic reticulum (ER)
      stress, are described. It is revealed that the trichloromethyl group greatly
      contributes to the activity. Based on the SAR results, salubrinal was converted
      into a biotinylated derivative which retains activity and can be used as a
      biological tool for target identification.

PMID- 16002289
TI  - Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput
      chemistry.
AB  - High-throughput screening of an array of biphenylmethylamines synthesised by high
      throughput solid-phase chemistry resulted in the identification of compounds with
      high-affinity for the 5-ht5A receptor. The structure-activity relationship within
      this series and further array synthesis led to the identification of the
      biphenylmethylamine derivative 11, a potent and selective 5-ht5A receptor
      antagonist.

PMID- 16002290
TI  - Lead optimization of 4-(dimethylamino)quinazolines, potent and selective
      antagonists for the melanin-concentrating hormone receptor 1.
AB  - The optimization of a series of 4-(dimethylamino)quinazoline antagonists of the
      melanin-concentrating hormone receptor 1 (MCH-R1) is described. The combination
      of the elaboration of both the linker portion and the terminal phenyl ring
      provided N-(cis-4-{[4-(dimethylamino)quinazolin-2-yl]amino}cyclohexyl)-3,4
      difluorobenzamide hydrochloride 28 (ATC0175), which showed excellent antagonist
      activity at the MCH-R1 (IC50 = 3.4 nM) as well as good selectivity over the Y5
      and the alpha2A receptors.

PMID- 16002291
TI  - Structure-based design and synthesis of novel non-zinc chelating MMP-12
      inhibitors.
AB  - A new class of MMP-12 inhibitors was discovered and optimized using structure
      based drug design methods. Modeling studies using a known MMP-12 crystal
      structure identified a new interaction mode for these new MMP-12 inhibitors.
      Further optimization resulted in the discovery of a compound displaying nanomolar
      activity against MMP-12 and which was co-crystallized with MMP-12.

PMID- 16002292
TI  - Differentiation of benign from malignant breast disease associated with screening
      detected microcalcifications using dynamic contrast enhanced magnetic resonance
      imaging.
AB  - Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) is an effective
      diagnostic modality for symptomatic breast disease. However, its role in
      evaluating clinically occult disease associated with mammographically detected
      microcalcification remains unclear. Women recalled following screening
      mammography with microcalcification had DCE-MRI examination of the breast. The
      data were evaluated subjectively and objectively using both empirical and 2
      compartment pharmacokinetic modelling techniques to evaluate signal intensity
      parameters. Eighty-eight patients aged 50-75 years (median 58) were recruited.
      Comparing malignant and benign lesions, the mean values in arbitrary units for
      the enhancement index at 1 min in the most enhancing 9-pixel square +/-1 standard
      deviation were 0.61+/-0.40 vs. 0.22+/-0.26 p=<0.001 with sensitivity,
      specificity, PPV, NPV and accuracy of 80.0%, 82.4%, 57.1%, 93.3% and 81.8%,
      respectively. The corresponding values attained by the radiologist were 75.0%,
      89.7%, 68.2%, 92.4% and 86.4%. DCE-MRI is able to differentiate malignant from
      benign clinically occult lesions associated with microcalcification and may
      therefore offer an alternative to open surgical biopsy for women with equivocal
      findings following initial triple assessment for microcalcification in the
      breast.

PMID- 16002293
TI  - Xenobiotic-metabolising enzymes in patients with adenocarcinoma of the breast:
      correlation with clinical stage and menopausal status.
AB  - Adenocarcinoma of the breast is the most common cancer in women worldwide and its
      incidence is increasing in most countries. The present study was designed to
      evaluate the relationship between different clinical stages and menopausal status
      using the activity of phase I and II carcinogen-metabolising enzymes in breast
      cancer patients. Fifty breast cancer patients clinically categorized as stage I,
      II and III, and as pre- and postmenopausal were chosen for the study. The levels
      of cytochrome P450 and b(5) and the activity of glutathione S-transferase (GST),
      gamma-glutamyl transpeptidase (GGT), DT-diaphorase (DTD) and NADPH diaphorase in
      tumour tissues and adjacent normal tissues were estimated. Enhanced levels of
      cytochrome P450 and b(5) and phase II enzyme activity were observed in breast
      tumour tissues compared with the corresponding uninvolved adjacent tissues
      irrespective of clinical stage and menopausal status of the patients. The
      magnitude of the changes in phase I and II enzyme status was, however, more
      pronounced in stage I and in premenopausal patients than in stage II and III and
      postmenopausal patients respectively. Our results suggest that the balance
      between phase I carcinogen activation and phase II detoxification systems may
      play an important role in the development of breast tumours.

PMID- 16002294
TI  - Children achieve adult-like sensory integration during stance at 12-years-old.
AB  - This study examined balance control in children to determine at what age the
      integration of sensory information in unperturbed stance is comparable to that of
      adults. In addition, it examined whether overall performance was related to age,
      gender and specific physical characteristics, such as height, weight and body
      mass index (BMI). Seventy-four female and 80 male children between the ages of 6
      and 12 years participated in the study, as well as 20 adults, aged 20-22 years.
      The Sensory Organization Test (SOT), a component of computerized dynamic
      posturography, was used to assess overall balance as well as the use of specific
      sensory information in maintaining stability. Analyses of variance revealed
      significant differences between equilibrium scores of 7- and 8-year-old and 11-
      and 12-year-old (p < .01), with only the 12-year-old participants achieving
      scores comparable to those of the adult group. A repeated-measures analysis of
      variance comparing the use of different sensory information across age and gender
      groups revealed that while all groups demonstrated mature use of somatosensory
      information, children under 11 did not use visual information as effectively as
      adults, and only the 12-year-old group demonstrated adult-like use of vestibular
      information. Correlational analyses revealed a moderate correlation between
      composite balance scores and age, r(152) = .38, p < .001, but poor correlations
      between the composite equilibrium score and height, weight and BMI (r < .13, p >
      .15). Multiple regression analysis revealed that while physical characteristics
      accounted for approximately 20% of the variability in the composite equilibrium
      score, age alone accounted for the largest single contribution to the variance
      (16%). These results support recent findings suggesting that children do not
      demonstrate adult-like use of sensory information prior to age 12 years.

PMID- 16002295
TI  - Pumps, paradoxes and ploughshares: mechanism of the MCM2-7 DNA helicase.
AB  - In eukaryotes, numerous lines of evidence have coalesced into a convincing case
      that the MCM2-7 complex - a heterohexameric ATPase - is the replicative DNA
      helicase. However, almost nothing is known about how this enzyme functions in a
      cellular context. Some models for the mechanism of the MCM2-7 helicase envision
      that it translocates along single-stranded DNA (ssDNA), whereas, more recently,
      it is has been suggested that it pumps double-stranded DNA (dsDNA) through its
      central channel. In particular, one model in which a double hexamer of MCM2-7
      pumps dsDNA towards the hexamer interface and extrudes ssDNA laterally as a
      result of torsional strain is gaining popularity. Here, we discuss existing
      models and propose a new variation in which a single hexamer is the functional
      unit of the helicase. Duplex DNA is pumped into MCM2-7 and, as it emerges from
      the complex, a rigid protein that we term the 'ploughshare' splits the duplex.

PMID- 16002296
TI  - Use of Leeds-Keio connective tissue prosthesis (L-K CTP) for reconstruction of
      deficient extensor mechanism with total knee replacement.
AB  - PURPOSE: This study was carried out in order to assess the results of
      reconstruction of a deficient extensor mechanism in the presence of a total knee
      replacement (TKR) using the Leeds-Keio Connective Tissue Prosthesis (L-K CTP).
      METHODS AND RESULTS: The L-K CTP is available as flat tapes constructed from
      polyester in an open weave structure. It was used to reinforce and reconstruct
      the extensor mechanism, which was deficient in three patients who had undergone
      total knee replacement or were about to undergo total knee replacement. Two cases
      had extensor mechanism deficiency as a complication following total knee
      replacement while the third case had extensor mechanism deficiency at the time of
      the primary knee replacement. The average follow-up was 2 years (range of follow
      up was 12 to 48 months). All three cases showed good results with no extension
      lag and good range of movement at follow up. CONCLUSION: The use of L-K CTP for
      reconstruction of the knee extensor mechanism offers a good option for the
      management of the uncommon but difficult problem of extensor mechanism deficiency
      in patients with a total knee replacement.

PMID- 16002297
TI  - Synthesis and evaluation of bifunctional nitrocatechol inhibitors of pig liver
      catechol-O-methyltransferase.
AB  - Bifunctional compounds were tested in vitro as potential inhibitors of pig liver
      catechol-O-methyltransferase (COMT) with respect to the catechol substrate 4
      [(3,4-dihydroxyphenyl)azo]benzenesulfonate. The bifunctional compounds were a
      composite of either two nitrocatechols or one nitrocatechol and one phenol,
      linked by amide bonds to a spacer unit comprising two to five methylene groups.
      The unsymmetrical compounds N-[2-(4-hydroxybenzoylamine)ethyl]-3,4-dihydroxy-5
      nitrobenzamide], N-[3-(4-hydroxybenzoyl-amine)propyl]-3,4-dihydroxy-5
      nitrobenzamide] and N-[5-(4-hydroxybenzoylamine)pentyl]-3,4-dihydroxy-5
      nitrobenzamide] demonstrated strong inhibitory action against COMT with K(i)
      values in the 100 nM range. In comparison, the monofunctional nitrocatechol
      analogues of these compounds had K(i) values that were significantly higher.

PMID- 16002298
TI  - Synthesis of novel 4-substituted-7-trifluoromethylquinoline derivatives with
      nitric oxide releasing properties and their evaluation as analgesic and anti
      inflammatory agents.
AB  - Six derivatives of the general formula 2- or 4-(7-trifluoromethylquinolin-4
      ylamino) benzoic acid N'-(nitrooxyacetyl or propionyl) hydrazide and an oxime of
      the formula 1-[4-(7-trifluoromethylquinolin-4-ylamino)phenyl]ethanone oxime were
      synthesized and tested for their in vivo anti-inflammatory, analgesic, and
      ulcerogenic properties, as well as their in vitro nitric oxide release ability.
      Compound 2-(7-trifluoromethylquinolin-4-ylamino)benzoic acid N'-(2-nitrooxy
      propionyl)hydrazide 12 showed an anti-inflammatory activity comparable to that of
      indomethacin in the carrageenan-induced rat paw edema test, and equipotency to
      glafenine in the acetic acid mice induced writhing model at 100mg/kg p.o.,
      respectively. All the final compounds showed no tendency to induce stomach
      ulceration in rats; nitric oxide seems to contribute to their excellent safety
      profile.

PMID- 16002299
TI  - Binding studies and GRIND/ALMOND-based 3D QSAR analysis of benzothiazine type
      K(ATP)-channel openers.
AB  - For seventeen 1,4-benzothiazine potassium channel openers, we performed binding
      studies in rat aortic smooth muscle cells and cardiomyocytes, compared their
      binding affinities with published relaxation data, and derived 3D-QSAR models
      using GRIND/ALMOND descriptors. Binding affinities in smooth muscle cells range
      from a pK(D) of 4.76 for compound 3e to 9.10 for compound 4c. Comparison of data
      for smooth muscle relaxation and binding shows preferentially higher pEC(50)s for
      the former. In cardiomyocytes, pK(D) values range from 4.21 for 3e to 8.16 for
      4c. 3D-QSAR analysis resulted in PLS models of two latent variables for all three
      activities with determination coefficients of 0.97 (smooth muscle relaxation) and
      0.94 (smooth muscle cells- and cardiomyocytes-binding). Internal validation
      yielded q(2) values of 0.69, 0.66, and 0.64. The carbonyl on the N-4 substituent,
      the hydrogen bond acceptor at C-6, the five-membered ring at N-4, and the gem
      dimethyls mainly guide strong binding and strong smooth muscle relaxation.

PMID- 16002300
TI  - Modulation of tyrosine phosphorylation signalling pathways by 1alpha,25(OH)2
      vitamin D3.
AB  - Hormonally active vitamin D(3), 1alpha,25(OH)(2)D(3), interacts with the classic
      vitamin D nuclear receptor that regulates gene transcription and with a putative
      cell membrane receptor that mediates rapid biological responses.
      1alpha,25(OH)(2)D(3) actions on target tissues regulate: mineral metabolism and
      intracellular Ca(2+); protein kinase cascades leading to cell proliferation,
      differentiation and apoptosis; muscle growth and contractility; and the immune
      system. There is evidence for underlying 1alpha,25(OH)(2)D(3)-mediated protein
      tyrosine phosphorylation signalling in bone, intestine, muscle, epidermal and
      cancer cells. Extracellular-signal-regulated kinases-1/2, p38 and/or c-jun N
      terminal kinase pathways play important roles in mediating 1alpha,25(OH)(2)D(3)
      actions. Studies to elucidate key regulatory metabolic steps and crosstalk sites
      in these pathways would enhance our understanding of the significance of tyrosine
      phosphorylation cascades in normal 1alpha,25(OH)(2)D(3) physiology,
      pathophysiology and pharmacology.

PMID- 16002301
TI  - A KiSS to remember.
AB  - The Kiss1 gene encodes a family of neuropeptides named kisspeptins, which bind to
      a (former orphan) G-protein-coupled receptor called GPR54. Recent investigations
      suggest that kisspeptins play a vital role in regulating the secretion of
      gonadotropin-releasing hormone (GnRH). New evidence confirms that kisspeptins act
      through GPR54 to stimulate GnRH secretion. Kisspeptins and GPR54 are crucial for
      pubertal maturation in the primate. Kiss1 mRNA is differentially regulated by sex
      steroids in distinct hypothalamic nuclei.

PMID- 16002302
TI  - Membrane rafts as potential sites of nongenomic hormonal signaling in prostate
      cancer.
AB  - Recent evidence indicates that nuclear receptors for steroid hormones can signal
      by nongenomic mechanisms that operate independently of their transcription
      function. These signal-transduction processes occur within seconds to minutes
      after initiation with agonist and involve interactions between nuclear receptors
      and other signaling proteins in the cytoplasm and at membrane surfaces. This
      review provides an overview of published information on possible nongenomic
      activities of the androgen receptor (AR) and other nuclear receptors, focusing on
      the potential involvement of these processes in prostate cancer. We discuss the
      hypothesis that the cholesterol-rich lipid-raft compartment(s) of cancer-cell
      membranes might provide privileged sites for nongenomic signals mediated by the
      AR.

PMID- 16002303
TI  - New therapeutic options for the metabolic syndrome: what's next?
AB  - The metabolic syndrome (MSX), characterized by obesity, insulin resistance,
      dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and
      mortality. It has recently been hypothesized that MSX and type 2 diabetes are
      caused by triglyceride and long-chain fatty acid accumulation in liver, muscle,
      pancreatic islets and selected brain areas. This lipocentric approach is
      integrated with analysis of inflammation associated with end-organ damage,
      including the vascular wall. Genes and proteins contributing to insulin
      resistance, beta cell dysfunction and vascular wall damage have been identified.
      Transcription factors and coactivators, including peroxisome proliferator
      activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating
      insulin resistance and accelerating vascular wall inflammation, and represent
      promising therapeutic targets. New pharmacological strategies include dual
      PPARalpha/gamma agonists, drugs with pleiotropic effects or combination
      therapies.

PMID- 16002304
TI  - Pharmacokinetic interaction between diltiazem and morin, a flavonoid, in rats.
AB  - The present study aims to investigate the effect of morin, a flavonoid, on the
      pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in
      rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were
      determined in rats after an oral administration of diltiazem (15 mg kg(-1)) to
      rats in the presence and absence of morin (1.5, 7.5 and 15 mg kg(-1)). Compared
      to the control given diltiazem alone, the C(max) and AUC of diltiazem increased
      by 30-120% in the rats co-administered with a 1.5 or 7.5 mg kg(-1) of morin,
      while there was no significant change in T(max) and terminal plasma half-life
      (T(1/2)) of diltiazem in the presence of morin. Consequently, absolute and
      relative bioavailability values of diltiazem in the rats co-administered with
      morin were significantly higher (p<0.05) than those from the control group.
      Metabolite-parent AUC ratio in the presence of morin (7.5 mg kg(-1)) decreased by
      30% compared to the control group, implying that coadministration of morin could
      be effective to inhibit the CYP3A4-mediated metabolism of diltiazem. In
      conclusion, the presence of morin significantly enhanced the oral exposure of
      diltiazem, suggesting that concurrent use of morin or morin-containing dietary
      supplement with diltiazem should require close monitoring for potential drug
      interactions.

PMID- 16002305
TI  - BOLD MRI responses to repetitive TMS over human dorsal premotor cortex.
AB  - Functional magnetic resonance imaging (fMRI) studies in humans have hitherto
      failed to demonstrate activity changes in the direct vicinity of transcranial
      magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory
      feedback or a spread of excitation. In order to investigate the underlying
      activity changes at the site of stimulation as well as in remote connected
      regions, we applied short trains of high-intensity (110% of resting motor
      threshold) and low-intensity (90% of active motor threshold) repetitive TMS
      (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal
      premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the
      stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI
      responses were observed with rTMS at both 90% and 110% RMT in connected brain
      regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory
      cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and
      caudate nucleus. Responses were generally smaller during low-intensity rTMS. The
      results indicate that short trains of TMS can modify local hemodynamics in the
      absence of overt motor responses. In addition, premotor rTMS cannot only
      effectively stimulate cortico-cortical but also cortico-subcortical connections
      even at low stimulation intensities.

PMID- 16002306
TI  - Development of a 3-D, multi-nuclear continuous wave NMR imaging system.
AB  - The development of a 3-D, multi-nuclear continuous wave NMR imaging (CW-NMRI)
      system is described and its imaging capability is demonstrated on a range of
      materials exhibiting extremely short T(2) relaxation values. A variety of
      radiofrequency resonators were constructed and incorporated into a new gradient
      and field offset coil assembly, while the overall system design was modified to
      minimise microphonic noise which was present in an earlier prototype system. The
      chemically combined (27)Al in a high temperature refractory cement was imaged,
      and the CW-NMRI system was found to be sensitive to small differences in (27)Al
      content in these samples. The penetration of (23)Na in salt water into samples of
      ordinary Portland cement (OPC) was investigated, with enhanced uptake observed
      for samples with larger pore size distributions. The solid (13)C component in a
      carbonated cement sample was also imaged, as were the (7)Li nuclei in a sample of
      powdered Li(2)CO(3). A spatial resolution of 1mm was measured in an image of a
      rigid polymeric material exhibiting a principal T( *)(2) value of 16.3 micros.
      Finally, a high-resolution 3-D image of this rigid polymer is presented.

PMID- 16002307
TI  - Analyzing different parameters of steered molecular dynamics for small membrane
      interacting molecules.
AB  - The aim of this report is two-fold: First, to show the applicability of the
      Steered Molecular Dynamics (SMD) methodology for analyzing non-specific
      interactions governing the membrane affinity process of small biological
      molecules. Second, to point out a correlation between the system response and
      certain combinations of the SMD parameters (spring-elastic-constant and pulling
      group). For these purposes, a simplified membrane model was used, modeled as a
      non-polar region limited by two polar aqueous media in a continuous dielectric
      representation. Polarization-induced effects at both interfaces were taken into
      account by the "electrostatic images" method. To perform SMD simulations a
      harmonic external force, representing a spring acting on a selected atom, forces
      the molecule to "break" its interaction with the surrounding environment by
      extracting it out of the membrane. With this approach, small molecules and
      peptides, with known affinity for the membrane environment, were studied: the
      zwitterionic tryptophan residue and a pentapeptide AcWLKLL. The SMD parameters,
      spring-elastic-constant and pulling-group, were varied and combined in order to
      analyze the systems responses in each case. It was observed that, the spring
      stiffness was crucial to reveal specific events that occur during the molecule
      behavior; hence, it was directly responsible for the sensitivity of this
      methodology. The pulling-group selected highly influenced on the reaction
      pathway, a fact that it was not observed with other parameters; consequently,
      force profiles are like the "fingerprints" of these induced pathways. The
      potential profile for the tryptophan was recovered from the SMD simulations being
      in good agreement with that estimated by an approximation method. With this
      rather simple model approach, SMD methodology has proven to be suitable for
      revealing the main interactions that govern the membrane affinity processes of
      small molecules and peptides.

PMID- 16002308
TI  - Postprandial morphological response of the intestinal epithelium of the Burmese
      python (Python molurus).
AB  - The postprandial morphological changes of the intestinal epithelium of Burmese
      pythons were examined using fasting pythons and at eight time points after
      feeding. In fasting pythons, tightly packed enterocytes possess very short
      microvilli and are arranged in a pseudostratified fashion. Enterocyte width
      increases by 23% within 24 h postfeeding, inducing significant increases in
      villus length and intestinal mass. By 6 days postfeeding, enterocyte volume had
      peaked, following as much as an 80% increase. Contributing to enterocyte
      hypertrophy is the cellular accumulation of lipid droplets at the tips and edges
      of the villi of the proximal and middle small intestine, but which were absent in
      the distal small intestine. At 3 days postfeeding, conventional and environmental
      scanning electron microscopy revealed cracks and lipid extrusion along the narrow
      edges of the villi and at the villus tips. Transmission electron microscopy
      demonstrated the rapid postprandial lengthening of enterocyte microvilli,
      increasing 4.8-fold in length within 24 h, and the maintaining of that length
      through digestion. Beginning at 24 h postfeeding, spherical particles were found
      embedded apically within enterocytes of the proximal and middle small intestine.
      These particles possessed an annular-like construction and were stained with the
      calcium-stain Alizarine red S suggesting that they were bone in origin. Following
      the completion of digestion, many of the postprandial responses were reversed, as
      observed by the atrophy of enterocytes, the shortening of villi, and the
      retraction of the microvilli. Further exploration of the python intestine will
      reveal the underlying mechanisms of these trophic responses and the origin and
      fate of the engulfed particles.

PMID- 16002309
TI  - Determination of functional interactions among signalling pathways in Escherichia
      coli K-12.
AB  - Interaction among different signalling pathways has been noted repeatedly.
      However, no systematic method has been developed to identify and quantify such
      interactions. Here we reported that network component analysis (NCA) was able to
      determine interactions among various signalling pathways in Escherichia coli K-12
      based on known transcription factor (TF)-promoter connectivity information and
      microarray data from genetic knockout strains. The TF activities determined from
      NCA allow the quantitation of functional interactions, barring gross errors in
      the connectivity and microarray data. By using a robust statistical test, 37
      pairs of functional interactions were identified. Eighteen interaction pairs
      confirmed previous implications, while 19 others represent new predictions. These
      results demonstrate that the functional interactions among various signalling
      pathways may be rather significant. With reasonable TF-promoter connectivity, NCA
      coupled with genetic knockouts and microarray experiments provides a systematic
      way to elucidate interaction networks. As this approach cannot distinguish
      between cross-talks and unidentified direct regulation, the results should
      provide incentives for further experimental testing.

PMID- 16002310
TI  - Lactobacilli in the intestinal microbiota of Swedish infants.
AB  - Lactobacillus colonisation was examined in 112 Swedish infants. Faecal samples
      obtained at 1, 2, 4 and 8 weeks and at 6, 12 and 18 months of age were cultivated
      quantitatively on Rogosa agar. Lactobacilli were speciated by PCR and typed to
      the strain level by randomly amplified polymorphic DNA (RAPD). Lactobacilli
      reached a peak at 6 months when 45% of the infants were colonised. L. rhamnosus
      and L. gasseri were the most common species in this period. Colonisation by
      lactobacilli in general (P < 0.01) and L. rhamnosus in particular (P < 0.05) was
      more common in breast-fed than in weaned infants at 6 months of age.
      Lactobacillus isolation reached a nadir of 17% by 12 months (P < 0.0001), but
      increased to 31% by 18 months of age P < 0.05). The food-related species L.
      paracasei, L. plantarum, L. acidophilus and L. delbrueckii dominated in this
      second phase. A single strain persisted for at least 3 weeks in 17% of the
      infants during the first 6 months, most commonly L. rhamnosus. Lactobacillus
      population counts in colonised infants increased from 10(6.4) cfu/g at 1 week to
      10(8.8) cfu/g at 6 months, and then dropped to 10(5.4) cfu/g faeces at 12 months
      of age. Lactobacillus colonisation was not significantly related to delivery
      mode, or to presence of siblings or pets in the household. Our results suggest
      that certain Lactobacillus species, especially L. rhamnosus, thrive in the
      intestinal flora of breast-fed infants. After weaning they are replaced by other
      Lactobacillus species of types found in food.

PMID- 16002311
TI  - Cortisol and susceptibility to malaria during pregnancy.
AB  - We measured cortisol and prolactin concentrations in the peripheral venous blood
      of 23 non-pregnant and 59 pregnant Gabonese women from the second trimester of
      pregnancy until delivery. Cortisol concentrations were significantly higher in
      primigravidae women than in multigravidae women between 20 and 25 weeks'
      gestational age (166 vs. 132 ng/ml, respectively), between 28 and 37 weeks (226
      vs. 161 ng/ml) and at delivery (287 vs. 188 ng/ml). Conversely, plasma prolactin
      levels were highest in multigravidae women. Cortisol and prolactin concentrations
      both increased with the period of pregnancy (P = 0.01 and P < 0.01,
      respectively), suggesting that a sustained increase in cortisol level underlies
      the increased susceptibility of pregnant women, particularly primigravidae women,
      to malaria. In support of this hypothesis, we found a significant association
      between cortisol concentration and Plasmodium falciparum infection, on the one
      hand, and strong correlations with parasite load in P. falciparum-infected
      primigravidae women, on the other hand (rho between 0.35 and 0.45 with P < 0.01).

PMID- 16002312
TI  - High levels of circulating cardiac proteins indicate cardiac impairment in
      African children with severe Plasmodium falciparum malaria.
AB  - A role of the heart in the pathophysiology of severe Plasmodium falciparum
      malaria has recently been suggested. The objective of the present study was to
      substantiate this finding in a large group of African children and to correlate
      results with metabolic conditions in these children. Furthermore, the impact of a
      potential cardiac impairment on outcome in severe cases was assessed. Results may
      have important implications on the currently ongoing debate on fluid management
      in severe malaria patients. Plasma levels of N-terminal pro-brain natriuretic
      peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), myoglobin
      and creatine kinase muscle-brain (CK-MB) were compared in 400 African children
      with severe and mild falciparum malaria. Plasma levels of these markers were
      correlated with lactate and glucose blood levels, indicators for hypovolemia, and
      with clinical outcome. Children suffering from severe malaria and children who
      died (n = 22) exhibited high to very high levels of cardiac markers,
      respectively. Cardiac factors themselves were not predictive of fatal outcome,
      while, in multivariate analysis, lactic acidosis was the most important
      biochemical predictor of death in the severe malaria group. Lactic acidosis and
      hypoglycemia, however, result in cardiac impairment as defined by elevated levels
      of circulating cardiac proteins. Our results point to hypovolemia as a major
      underlying cause of lactic acidosis and hypoglycemia in African children with
      severe falciparum malaria. These deleterious metabolic conditions contribute to
      myocardial affection which was evident but not predictive per se of fatal
      outcome.

PMID- 16002313
TI  - The natural history of Ebola virus in Africa.
AB  - Several countries spanning the equatorial forest regions of Africa have had
      outbreaks of Ebola hemorrhagic fever over the last three decades. This article is
      an overview of the many published investigations of how Ebola virus circulates in
      its natural environment, focusing on the viral reservoir, susceptible animal
      species, environmental conditions favoring inter-species transmission, and how
      the infection is transmitted to humans. Major breakthroughs have been made in
      recent years but many outstanding questions must be dealt with if we are to
      prevent human outbreaks by interfering with the viral life cycle.

PMID- 16002314
TI  - Induction of expression of bovine leukemia virus (BLV) in blood taken from BLV
      infected cows without removal of plasma.
AB  - The expression of bovine leukemia virus (BLV) is blocked at the transcriptional
      level during the so-called latency period. However, when peripheral blood
      mononuclear cells and B lymphocytes are isolated from BLV-infected animals and
      incubated in the presence of activating reagents, such as phorbol ester, the
      expression of BLV is markedly enhanced. Such "reactivation" is thought to play a
      crucial role in the spread of BLV from infected to uninfected cattle. In the
      present study, we found that the expression of BLV in samples of whole blood from
      BLV-infected cattle was activated immediately upon incubation at 37 degrees C and
      that such activation did not require the addition of any exogenous factors except
      for anticoagulants or the removal of blood cells from plasma. The expression of
      BLV was repressed by an inhibitor of protein kinase C (PKC), namely, H-7, and by
      a membrane-permeable chelator of Ca2+ ions, BAPTA/AM. We also found that several
      isotypes of PKC were translocated immediately from the cytoplasm to the membrane
      fraction upon incubation of whole blood at 37 degrees C. Our data suggest that
      the actual collection of blood and pathways that involve PKC and Ca2+ might play
      important roles in the reactivation of expression of BLV in blood from infected
      cattle.

PMID- 16002315
TI  - Analysis of ribosomal DNA internal transcribed spacer sequences of the Leishmania
      donovani complex.
AB  - To understand phylogenetic relationships of species and strains within the
      Leishmania donovani complex, we have analyzed the ribosomal DNA internal
      transcribed spacer (ITS) sequences of 27 Leishmania infantum, 2 Leishmania
      chagasi, 18 L. donovani and 5 Leishmania archibaldi strains of different
      zymodemes and geographical origin. Eight ITS sequence types were found. All
      detected sequence variation within ITS1 and ITS2 was based on 12 polymorphic
      microsatellites. The L. infantum strains from the Mediterranean region, China and
      L. chagasi from the New World formed a phylogenetic group well separated from the
      second main group including all strains from East Africa and India. Within the
      latter group three distinct phylogenetic subgroups could be differentiated: (1)
      L. donovani (Sudan/Ethiopia, China) + L. archibaldi (Sudan), (2) L. donovani
      (Sudan/Ethiopia) + L. infantum (Sudan) + L. archibaldi (Sudan/Ethiopia), and (3)
      L. donovani (Kenya, India). These groups are not consistent with previous species
      definitions based on isoenzyme analyses, e.g. L. infantum is polyphyletic and L.
      archibaldi is not supported as a distinct species. Two groups of Indian strains
      could be differentiated, one of which has an identical sequence type to the
      strains from Kenya. Three main lineages of strains can thus be differentiated in
      East Africa: two quite distantly related groups of strains from Sudan/Ethiopia,
      and a third group including all strains from Kenya, which is more closely related
      to part of the Indian strains than to any of the Sudanese/Ethiopian groups. The
      ITS sequence analysis presented here supports the need for revision of the
      taxonomy of the L. donovani complex.

PMID- 16002316
TI  - Liquid-phase adsorption and desorption of phenol onto activated carbons with
      ultrasound.
AB  - The effect of 48-kHz ultrasound on the adsorption and desorption of phenol from
      aqueous solutions onto coconut shell-based granular activated carbons was studied
      at 25 degrees C. Experiments were performed at different carbon particle sizes
      (1.15, 2.5, 4.0 mm), initial phenol concentrations (1.06-10.6 mol/m3), and
      ultrasonic powers (46-133 W). Regardless of the absence and presence of
      ultrasound, the adsorption isotherms were well obeyed by the Langmuir equation.
      When ultrasound was applied in the whole adsorption process, the adsorption
      capacity decreased but the Langmuir constant increased with increasing ultrasonic
      power. According to the analysis of kinetic data by the Elovich equation, it was
      shown that the initial rate of adsorption was enhanced after sonication and the
      number of sites available for adsorption was reduced. The effect of ultrasonic
      intensity on the initial rate and final amount of desorption of phenol from the
      loaded carbons using 0.1 mol/dm3 of NaOH were also evaluated and compared.

PMID- 16002317
TI  - Analysis of articular cartilage as a composite using nonlinear membrane elements
      for collagen fibrils.
AB  - To develop a composite fibre-reinforced model of the cartilage, membrane shell
      elements were introduced to represent collagen fibrils reinforcing the isotropic
      porous solid matrix filled with fluid. Nonlinear stress-strain curve of pure
      collagen fibres and collagen volume fraction were explicitly presented in the
      formulation of these membrane elements. In this composite model, in accordance
      with tissue structure, the matrix and fibril membrane network experienced
      dissimilar stresses despite identical strains in the fibre directions. Different
      unconfined compression and indentation case studies were performed to determine
      the distinct role of membrane collagen fibrils in nonlinear poroelastic mechanics
      of articular cartilage. The importance of nonlinear fibril membrane elements in
      the tissue relaxation response as well as in temporal and spatial variations of
      pore pressure and solid matrix stresses was demonstrated. By individual
      adjustments of the collagen volume fraction and collagen mechanical properties,
      the model allows for the simulation of alterations in the fibril network
      structure of the tissue towards modelling damage processes or repair attempts.
      The current model, which is based on a physiological description of the tissue
      structure, is promising in improvement of our understanding of the cartilage
      pathomechanics.

PMID- 16002318
TI  - In vitro measurements of temperature-dependent specific heat of liver tissue.
AB  - We measured the specific heat of liver tissue in vitro by uniformly heating liver
      samples between two electrodes. We insulated the samples by expanded polystyrene,
      and corrected for heat loss and water loss. The specific heat of the liver is
      temperature-dependent, and increases by 17% at 83.5 degrees C (p < 0.05),
      compared to temperatures below 65 degrees C. The average specific heat was 3411 J
      kg(-1)K(-1) at 25 degrees C, and 4187 J kg(-1)K(-1) at 83.5 degrees C. Water loss
      from the samples was significant above 70 degrees C, with approximately 20% of
      reduction in sample mass at 90 degrees C.

PMID- 16002319
TI  - Estimating population prevalence of psychiatric conditions by small area with
      applications to analysing outcome and referral variations.
AB  - This paper considers the development of estimates of mental illness prevalence
      for small areas and applications in explaining psychiatric outcomes and in
      assessing service provision. Estimates of prevalence are based on a logistic
      regression analysis of two national studies that provides model based estimates
      of relative morbidity risk by demographic, socio-economic and ethnic group for
      major psychiatric conditions; household/marital and area status also figure in
      the regression. Relative risk estimates are used, along with suitably
      disaggregated census populations, to make prevalence estimates for 354 English
      local authorities (LAs). Two applications are considered: the first involves
      analysis of variations in schizophrenia referrals and suicide mortality over
      English LAs that takes account of prevalence differences, and the second involves
      assessing hospital referral and bed use in relation to prevalence (for ages 16
      74) for a case study area, Waltham Forest in NE London.

PMID- 16002320
TI  - Identifying diabetes knowledge network nodes as sites for a diabetes prevention
      program.
AB  - This paper reports on the methods used and results of a study that identified
      specific places within a community that have the potential to be sites for a
      diabetes prevention program. These sites, termed diabetes knowledge network nodes
      (DKNNs), are based on the concept of socio-spatial knowledge networks (SSKNs),
      the web of social relationships within which people obtain knowledge about type 2
      diabetes. The target population for the study was working poor African Americans,
      Latinos, and European Americans of both sexes in a small rural southern town who
      had not been diagnosed with diabetes. Information was collected from a sample of
      121 respondents on the places they visited in carrying out their daily
      activities. Data on number of visits to specific sites, degree of familiarity
      with these sites, and ratings of sites as places to receive diabetes information
      were used to develop three categories of DKNNs for six subgroups based on
      ethnicity and sex. Primary potential sites of importance to one or more subgroups
      included churches, grocery stores, drugstores, the local library, a beauty salon,
      laundromats, a community service agency, and a branch of the County Health
      Department. Secondary potential sites included gas stations, restaurants, banks,
      and post offices. Latent potential sites included three medical facilities. Most
      of the DKNNs were located either in the downtown area or in one of two shopping
      areas along the most used highway that passed through the town. The procedures
      used in this study can be generalized to other communities and prevention
      programs for other chronic diseases.

PMID- 16002321
TI  - Characterization of human LNX, a novel ligand of Numb protein X that is
      downregulated in human gliomas.
AB  - Gliomas are major tumors of the central nervous system with a wide spectrum of
      different tumor types. Ligand of Numb protein X (LNX) is PDZ domain containing
      protein that interacts with cell fate determinant Numb. cDNA microarray analysis
      was used to determine the expression of 13,939 genes in a set of 18 gliomas. It
      showed that human LNX was downregulated in 100% of gliomas including low- and
      high-grade ones, which was confirmed by Northern blot. In situ hybridization
      analysis revealed that LNX was lowly expressed in cytoplasm of glioma cells.
      Thus, LNX might act as a diagnostic marker and a potential therapeutic target for
      glioma. Two-hybrid screen in yeast was used to identify human LNX interacting
      proteins important for LNX function. It showed that human LNX interacted with Ski
      interacting protein (SKIP) via PDZ domains. The co-immunoprecipitation results
      suggested that LNX interacted with SKIP in HEK293 cells. LNX could affect the
      subcellular localization of Numb, which indicated that LNX might function as a
      molecular anchor that localized Numb to the subcellular site of its interaction
      with Notch. The presence of multiple protein binding domains involved in signal
      transduction and interaction with Numb and SKIP suggested an important role for
      LNX in tumorogenesis.

PMID- 16002322
TI  - Roles of fascin in human carcinoma motility and signaling: prospects for a novel
      biomarker?
AB  - Fascin is a globular actin cross-linking protein that has a major function in
      forming parallel actin bundles in cell protrusions that are key specialisations
      of the plasma membrane for environmental guidance and cell migration. Fascin is
      widely expressed in mesenchymal tissues and the nervous system and is low or
      absent in adult epithelia. Recent data from a number of laboratories have
      highlighted that fascin is up-regulated in many human carcinomas and, in
      individual tissues, correlates with the clinical aggressiveness of tumours and
      poor patient survival. In cell culture, over-expression or depletion of fascin
      modulates cell migration and alters cytoskeletal organisation. The identification
      of biomarkers to provide more effective early diagnosis of potentially aggressive
      tumours, or identify tumours susceptible to targeted therapies, is an important
      goal in clinical research. Here, we discuss the evidence that fascin is
      upregulated in carcinomas, its contributions to carcinoma cell behaviour and its
      potential as a candidate novel biomarker or therapeutic target.

PMID- 16002323
TI  - Intuition and autism: a possible role for Von Economo neurons.
AB  - Von Economo neurons (VENs) are a recently evolved cell type which may be involved
      in the fast intuitive assessment of complex situations. As such, they could be
      part of the circuitry supporting human social networks. We propose that the VENs
      relay an output of fronto-insular and anterior cingulate cortex to the parts of
      frontal and temporal cortex associated with theory-of-mind, where fast intuitions
      are melded with slower, deliberative judgments. The VENs emerge mainly after
      birth and increase in number until age 4 yrs. We propose that in autism spectrum
      disorders the VENs fail to develop normally, and that this failure might be
      partially responsible for the associated social disabilities that result from
      faulty intuition.

PMID- 16002324
TI  - Doubts about double dissociations between short- and long-term memory.
AB  - Historically, psychologists and neuroscientists have distinguished between
      processes supporting memory for events across retention delays of several seconds
      (short-term memory, STM), and those supporting memory for events across longer
      retention delays of minutes or more (long-term memory, LTM). Dissociations
      reported in some neuropsychological studies have contributed to a popular view
      that there must be neurally distinct memory stores that differentially support
      STM and LTM. In this article, we review evidence from recent studies regarding
      dissociations between STM and LTM. We suggest that the evidence reveals problems
      with claims of selective STM or LTM impairments, which in turn questions whether
      theories of memory need to propose neurally distinct stores for short- and long
      term retention. We consider alternative ways to explain the neural mechanisms of
      memory across different retention intervals.

PMID- 16002325
TI  - High-throughput magnetic resonance imaging in mice for phenotyping and
      therapeutic evaluation.
AB  - High-throughput mouse magnetic resonance imaging (MRI) is seeing rapidly
      increasing demand in development of therapeutics. Recent advances including
      higher-field systems, new gradient and radio frequency coils and new pulse
      sequences, coupled with efficient animal preparation and data handling, allow
      high-throughput MRI under certain protocols. However, with current shifts from
      anatomic to functional and molecular imaging, innovative technology is required
      to meet new throughput demands. The first multiple mouse imaging strategies have
      provided a glimpse of the future state-of-the-art. However, the successful
      translation of standard clinical MRI technology to preclinical MRI is required to
      facilitate next-generation high-throughput MRI.

PMID- 16002326
TI  - Invasive Candida infections in the neonate.
AB  - Advances in medical therapy have increased premature infant survival. A rise in
      Candida infections in neonatal intensive care units (NICUs) has followed. Once
      considered a contaminant, Candida is now recognized as a major cause of mortality
      and morbidity within these units. We will examine what is known about the
      epidemiology, risk factors and end-organ involvement of Candida infections with a
      focus on invasive disease. In addition, diagnostic alternatives to traditional
      blood culture, experience with antifungal agents for prophylaxis and therapeutic
      options, including newer antifungal agents, will be presented.

PMID- 16002327
TI  - Mitochondrial DNA point mutations and a novel deletion induced by direct low-LET
      radiation and by medium from irradiated cells.
AB  - Radiation damage incurred by nuclear DNA is well documented and interest is
      increasing in the properties of 'bystander' factor(s) and their ability to induce
      radiation-like damage in cells never exposed to radiation. 'Bystander' and direct
      low-LET radiation effects on the mitochondria, and more particularly the
      mitochondrial genome are less well understood. In this study HPV-G cells (a human
      keratinocyte cell line derived from human neonatal foreskin transfected with the
      HPV-16 virus) were exposed to either gamma-radiation doses as low as 5 mGy and up
      to 5 Gy from a 60Co teletherapy unit, or to growth medium taken from similarly
      irradiated cells, i.e. irradiated cell conditioned medium (ICCM). Mutation and
      deletion analysis was performed on mitochondrial DNA (mtDNA) 4-96 h after
      exposure. Primers flanking the so-called mitochondrial 'common deletion' were
      employed to assess its possible induction. Single-strand conformation
      polymorphism (SSCP) analysis was conducted to identify induced point mutations.
      The relative mitochondrial number per cell was analysed by semi-quantitative PCR
      (sqPCR). Results indicate the induction of a relatively novel deletion in the
      mitochondrial genome as early as 12 h after direct exposure to doses as low as
      0.5 Gy and 24 h after exposure to 0.5-Gy ICCM. SSCP analysis identified the
      induction of point mutations, in a non-consistent manner, in only the D-loop
      region of the mitochondrial genome and only in cells exposed to 5 Gy, and neither
      in cells exposed to lower doses of direct radiation nor in those exposed to ICCM.
      SqPCR also identified an increase in the number of mitochondria per cell after
      both exposure to low level gamma-radiation and ICCM, indicative of a possible
      mechanism to respond to mitochondrial stress by increasing the number of
      mitochondria per cell.

PMID- 16002328
TI  - 5-Aminosalicylic acid reverses endosulfan-induced testicular toxicity in male
      rats.
AB  - Pre-treatment with 5-aminosalicylic acid (5-ASA) significantly reduced sperm
      shape abnormalities in endosulfan-treated rats. The number of abnormal sperm in
      the epididymis was markedly increased by endosulfan treatment but pre-treatment
      with 5-ASA kept these values close to normal. Treatment with 5-ASA at a dose of
      25 mg/kg bw was more effective in reducing sperm-shape abnormality and sperm
      count than at a dose of 50 mg/kg bw. Endosulfan significantly increased the level
      of lactate dehydrogenase (LDH) in rats but a marked decrease was observed upon
      pre-treatment with 25 mg/kg bw 5-ASA. Changes in plasma testosterone levels were
      not significantly correlated with 5-ASA pre-treatment but histopathological
      analysis of seminiferous tubules and Leydig cells showed significant protection
      from endosulfan-induced tissue damage such as necrosis. The population of Sertoli
      cells increased and the lumen of the seminiferous tubules contained a greater
      number of spermatids. There was a corresponding increase in the number of Leydig
      cells. A curative study with 5-ASA showed a similar protection from endosulfan
      induced toxicity and cellular damage, but the extent of protection was
      significantly lower.

PMID- 16002329
TI  - Children's exposure to environmental pollutants and biomarkers of genetic damage.
      I. Overview and critical issues.
AB  - In the last decade, molecular epidemiological studies have provided new
      perspectives on studying environmental risks in pediatric populations, based on
      the growing understanding that children may be more susceptible to toxicants than
      adults. Protecting children's health is a social priority, and specific research
      programs have been initiated with this purpose in the United States and Europe.
      These programs address the development of (i) less invasive methods for
      biological specimens collection, (ii) specific tools for interpretation and
      validation of biomarkers, (iii) methods for translating biomarker results into
      intervention strategies and for integrating them with environmental monitoring
      and health data, (iv) optimal ways to obtain consent and provide information to
      children and/or their parents participating in the studies and (v) techniques for
      the effective communication with policy makers and the public. Critical issues in
      children's environmental research discussed in this paper include specific needs
      of study design, exposure assessment, sample collection and ethics. Special
      consideration is given to the autonomy of the child in giving consent, the
      details and nature of the information provided, and the need to warrant
      controlled access to sensitive information. The use of incentives such as gifts
      and payment to ensure the participation of school-aged children is specifically
      discussed. Examples of field studies that are focused on the effects of
      pesticides, air pollution and formaldehyde are used to illustrate advantages and
      limitations of biomarker studies in children.

PMID- 16002330
TI  - Diagnosis of the primary amoebic meningoencephalitis due to Naegleria fowleri.
AB  - Trophozoites of the free-living amoeba, Naegleria fowleri, were isolated from the
      cerebrospinal fluid of meningoencephalitis patient. The infecting agent was
      identified as N. fowleri based on morphologic, serologic and molecular techniques
      carried out on the isolated organisms.

PMID- 16002331
TI  - Sequence variation can affect the performance of minor groove binder TaqMan
      probes in viral diagnostic assays.
AB  - A minor groove binder (MGB) TaqMan real-time PCR assay was developed for the
      detection of respiratory syncytial virus (RSV) in clinical specimens. Upon
      evaluation of the assay, notable differences were observed in the overall
      fluorescent response obtained from RSV positive specimens, with some linear
      amplification curves deviating only slightly from baseline fluorescence.
      Sequencing of the probes targets in these RSV strains revealed single base
      mismatches with the MGB TaqMan probe. Overall, these results highlight the
      usefulness of MGB TaqMan probes for the detection of mismatches, but suggest that
      MGB Taqman probes have limitations for routine screening for uncharacterised
      viral strains.

PMID- 16002332
TI  - Quantitative analysis of human papillomavirus type 16 in cervical neoplasm: a
      study in Chinese population.
AB  - BACKGROUND: Human papillomavirus (HPV) infection was recognized as a major causal
      factor for the development and progression of squamous intraepithelial lesions
      (SIL). It is possible to use HPV test for the detection of cervical lesions as an
      adjunct to cervical cytology. OBJECTIVES: To evaluate the relation between HPV 16
      viral load and the severity of cervical lesions in a Chinese population. METHODS:
      Study population was recruited from the colposcopy and general outpatient clinic.
      The presence of HPV 16 E6 and E7 in cytological specimens was detected using HPV
      16 specific polymerase chain reaction (PCR). The viral load in the specimens that
      were positive for HPV 16 specific PCR, was quantified by using real-time PCR
      assay. RESULTS: The study recruited 394 women, in which 148 were high-grade SIL
      (HG-L), 121 were low-grade SIL (LG-L) and 125 were Normal. Sufficient DNA
      integrity was proven in 347 samples. Among 121 positive cases for HPV 16, 70 were
      HG-L, 34 were LG-L and 17 were Normal. Using quantitative real-time PCR, the
      percentages of samples with greater DNA copies were found to increase with the
      severity of diseases. There was also a significant difference in DNA copies among
      the three groups (HG-L versus Normal, p<0.001; HG-L versus LG-L, p<0.001). Area
      under receiver operating characteristic (ROC) curve of the HG-L versus LG-L and
      Normal was 0.836 indicating that quantitative PCR had a good diagnostic value in
      differentiating HG-L from the LG-L and Normal groups. CONCLUSIONS: Our data
      suggested HPV 16 viral load was significantly related to the severity of cervical
      lesions. Evaluation of viral burden could be a potential clinical tool in
      management of cervical lesions.

PMID- 16002333
TI  - Information processing in severe disorders of consciousness: vegetative state and
      minimally conscious state.
AB  - OBJECTIVE: To study the presence of electrophysiological indicators of remaining
      cortical functions in patients with persistent vegetative state (PVS) and
      minimally conscious state (MCS). Previous electrophysiological and PET data
      indicated that some PVS patients have partially intact cortical processing
      functions. However, it remains unclear whether the reported patients were
      representative for PVS population or just some exceptional cases. METHODS: Event
      related brain responses to stimuli of different complexity levels, recorded in 98
      patients with extremely severe diffuse brain injuries, 50 of which in PVS. Four
      main indicators of cortical functions were: (i) N1-P2 complex as an index of
      simple, undifferentiated cortical processing; (ii) mismatch negativity as an
      index of pre-attentive, probably unconscious, cortical orientation; (iii) P3 wave
      as an index of deep cortical analysis of physical stimuli, and (iv) brain
      responses to semantic stimuli. RESULTS: Cortical responses were found in all PVS
      patients with a background EEG activity > 4 Hz. All responses investigated,
      including those to semantic stimuli that indicated comprehension of meaning,
      occurred significantly above chance, though less frequently than in patients with
      severe brain injuries who were conscious. CONCLUSIONS: Cortical responses were
      lacking in most patients with severe EEG slowing (< 4 Hz). Follow-up data
      revealed that the presence of a mismatch negativity, a short disease duration,
      and the traumatic etiology were related to a better outcome. SIGNIFICANCE: The
      data show that in a subpopulation of PVS patients with preserved thalamocortical
      feedback connections, remaining cortical information processing is a consistent
      finding and may even involve semantic levels of processing.

PMID- 16002334
TI  - Comparison of different outlier criteria in quantitative anal sphincter
      electromyography.
AB  - OBJECTIVE: Analysis based on 'outliers' has been demonstrated to be a useful
      adjunct to mean value analysis in quantitative needle electromyography (EMG).
      However, the outlier criteria applied have been arbitrarily chosen. The aim of
      the present study was to determine the most useful outlier criteria in motor unit
      potential (MUP) analysis. METHODS: The external anal sphincter (EAS) muscles were
      examined by multi-MUP analysis. From 115 muscles of 64 normative subjects, the
      0/100, 5/95, 10/90, 15/85, 20/80, and 25/75 percentile MUP parameter values were
      grouped individually. From these, the 5/95, 2.5/97.5, 1/99 and 0/100% confidence
      limits were determined. Thus, 24 sets of outlier limits were formed. To calculate
      sensitivity and specificity, data from 79 patients with cauda equina lesions (189
      muscles), and from 77 controls (119 muscles) were compared to normative outlier
      limits. RESULTS: Sensitivities were highest with outlier limits formed from the
      10-90 percentile ranges, followed by the 5-95 and 15-85 percentile ranges, while
      specificity was highest using the 15-85, followed by the 20-80, and 25-75
      percentile ranges. On direct head-to-head comparison the 10-90 percentile ranges
      were more sensitive and 5-95 were more specific. CONCLUSIONS: The study
      demonstrated considerable differences in the sensitivity and specificity of
      outlier limits calculated from different percentile ranges, with outlier criteria
      calculated from the 10-90 and from the 5-95 percentile ranges appearing to be the
      most useful for detection of neuropathy in the EAS muscle. SIGNIFICANCE: In
      future EAS muscle EMG I propose that outlier criteria calculated from the 10-90
      percentile ranges be used.

PMID- 16002335
TI  - Hippocampal-orbitofrontal connectivity in human: an electrical stimulation study.
AB  - OBJECTIVE: The identification of the pathways involved in seizure propagation
      remains poorly understood in humans. For instance, the respective role of the
      orbitofrontal cortex (OFC) and of the commissural pathways in the
      interhemispheric propagation of mesial temporal lobe seizures (mTLS) is a matter
      of debate. In order to address this issue, we have directly tested the functional
      connectivity between the hippocampus and the OFC in 3 epileptic patients
      undergoing an intra-cranial stereotactic EEG investigation. METHODS: Bipolar
      electrical stimulations, consisting of two series of 25 pulses of 1 ms duration,
      0.2 Hz frequency, and 3 mA intensity, were delivered in the hippocampus. Evoked
      potentials (EPs) were analysed for each series, separately. Grand average of
      reproducible EPs was then used to calculate latency of the first peak of each
      individual potential. RESULTS: Hippocampal stimulations evoked reproducible
      responses in the OFC in all 3 patients, with a mean latency of the first peak of
      222 ms (range: 185-258 ms). CONCLUSIONS: Our data confirm a functional
      connectivity between the hippocampus and the OFC in human. SIGNIFICANCE: This
      connectivity supports the potential role of the OFC in the propagation of mTLS.

PMID- 16002336
TI  - An expanding role for mTOR in cancer.
AB  - Rapamycin, a valuable drug with diverse clinical applications, inhibits mTOR
      (mammalian target of rapamycin), which is a protein kinase that controls cell
      growth by regulating many cellular processes, including protein synthesis and
      autophagy. The sensitivity of select tumor cells to rapamycin has ignited
      considerable excitement over its potential as an anti-cancer therapeutic. Recent
      findings identified a rapamycin-insensitive function of mTOR in regulating a cell
      survival pathway that is hyperactive in many cancers, particularly those with
      elevated PtdIns3K signaling or harboring mutations in the tumor suppressor PTEN
      (phosphatase and tensin homolog deleted on chromosome 10). These new findings
      suggest that targeting this function of mTOR might have broader applications in
      cancer therapy. In this article, we re-evaluate mTOR signaling, suggesting a more
      central role for mTOR in cancers with defective PtdIns3K-PTEN signaling and
      conceptually discuss these implications in the context of drug discovery.

PMID- 16002338
TI  - Information sharing and collateral damage.
AB  - Recent studies have revealed a novel mechanism of antigen cross-presentation by
      intercellular peptide transfer through gap junctions, which provides new insight
      about how the immune system recognizes and destroys viruses and tumor cells. At
      the site of infection or tumorigenesis, gap junctions provide an "information
      sharing" channel through which viral- and tumor-derived peptides are transferred
      to professional antigen-presenting cells (APCs), leading to naive T-cell
      stimulation. Similarly, gap-junction-mediated peptide transfer from infected or
      malignant cells to neighboring cells incurs "collateral damage" by cytotoxic T
      cells, thereby limiting the spread of viruses or the progression of tumors.

PMID- 16002337
TI  - The TIM gene family regulates autoimmune and allergic diseases.
AB  - The recently identified TIM gene family encodes cell-surface receptors that are
      involved in the regulation of Th1- and Th2-cell-mediated immunity. Tim-3 protein
      is specifically expressed on Th1 cells and negatively regulates Th1 responses,
      whereas Tim-2 is preferentially expressed in Th2 cells. Tim-1, previously
      identified as the hepatitis A virus receptor, co-stimulates T-cell expansion and
      cytokine production. Tim-4, which is preferentially expressed on mature dendritic
      cells, is the ligand for Tim-1. In mouse models of asthma and multiple sclerosis,
      affecting the function of Tim molecules altered disease phenotype. Because TIM
      molecules are differentially expressed on effector Th1 and Th2 cells, further
      understanding of the mechanisms by which they regulate Th1- and Th2-effector
      functions will probably provide opportunities for the therapeutic modulation of
      immune-mediated diseases.

PMID- 16002339
TI  - The case for immunosuppression in clinical gene transfer.

PMID- 16002340
TI  - The effect of ventricular pacing on measurements of left ventricular function: a
      comparison between echocardiographic methods and with radionuclide
      ventriculography.
AB  - AIMS: Different methods exist for measuring left ventricular function
      echocardiographically; each may be error prone due to the abnormal pattern of
      ventricular activation during pacing. METHODS AND RESULTS: Echocardiography was
      undertaken on 307 patients with permanent pacemakers; a subset of 57 underwent
      radionuclide ventriculography. Intrinsic and paced beats were analysed for left
      ventricular function by: Simpson's bi-plane, Teicholz M-mode, wall-motion scoring
      and 'eyeball' assessment. Agreement between techniques and with radionuclide
      ventriculography were compared according to intrinsic or paced beats.
      Echocardiographic measures of ejection fraction give mean values 5% higher than
      radionuclide ventriculography (Simpson's 30+/-9%, vs. Teicholz 30+/-13% vs.
      radionuclide ventriculography 25+/-9%, p=0.03). Agreement between Simpson's,
      Teicholz and radionuclide ventriculography by Bland-Altman analysis showed poor
      agreement (Simpson's vs. Teicholz range (4xSD)=57%, Simpson's vs. radionuclide
      ventriculography=36%, Teicholz vs. radionuclide ventriculography=46%, p=0.02),
      the level of agreement deteriorates with ventricular pacing (Simpson's vs.
      Teicholz range=61%, Simpson's vs. radionuclide ventriculography=34%, Teicholz vs.
      radionuclide ventriculography=47%, p=0.02). The correlation between wall motion
      analysis and radionuclide ventriculography is moderately poor (all subjects
      r=0.58, ventricular pacing r=0.52, not pacing r=0.66). CONCLUSION:
      Echocardiography and radionuclide ventriculography are the only non-invasive
      techniques to assess left ventricular function in the paced population. Results
      are poorly interchangeable and the accuracy of any comparison dependent on the
      underlying rhythm.

PMID- 16002341
TI  - The protective effect of mitral stenosis on the embolization of a free-floating
      left atrial myxoma.
AB  - Mitral stenosis associated with free left atrial myxoma is very rare. A free
      myxoma is life-threatening when incarcerated in the mitral orifice or if
      embolization of the whole tumor occurs. We report a case of a female patient with
      moderate mitral stenosis and a detached left atrial myxoma. The myxoma was
      spherical, solid and smooth-surfaced. Mitral stenosis prevented the exit of the
      tumor from the left atrium and a possible fatal outcome. The tumor was surgically
      removed and mitral commissurotomy was successfully performed. Histological
      analysis confirmed the diagnosis of myxoma.

PMID- 16002342
TI  - Systemic and pulmonary embolization in a patient with patent ductus arteriosus.
AB  - We report on a patient with unrecognized patent ductus arteriosus and infective
      endocarditis of the aortic valve with septic embolization to the right pulmonary
      artery and the coronary tree.

PMID- 16002343
TI  - Biological and immunological properties of the venom of Bothrops alcatraz, an
      endemic species of pitviper from Brazil.
AB  - Bothrops alcatraz is a new pitviper species derived from the Bothrops jararaca
      group, whose natural habitat is situated in Alcatrazes Archipelago, a group of
      marine islands near Sao Paulo State coast in Brazil. Herein, the biological and
      biochemical properties of venoms of four adult specimens of B. alcatraz were
      examined comparatively to a reference pool of Bothrops jararaca venom. Both
      venoms showed similar activities and electrophoretic patterns, but B. alcatraz
      venom showed three protein bands of molecular masses of 97, 80 and 38 kDa that
      were not present in B. jararaca reference venom. The i.p. median lethal dose of
      B. alcatraz venom ranged from 5.1 to 6.6 mg/kg, while it was 1.5 mg/kg for B.
      jararaca venom. The minimum hemorrhagic dose of B. jararaca venom was 0.63,
      whereas 2.28 mug/mouse for B. alcatraz venom. In contrast, B. alcatraz venom was
      more potent in regard to procoagulant and proteolytic activities. These
      differences were supported by western blotting and neutralization tests,
      employing commercial bothropic antivenom, which showed that hemorrhagic and
      lethal activities of B. alcatraz venom were less effectively inhibited than B.
      jararaca venom. Such results evidence that B. alcatraz shows quantitative and
      qualitative differences in venom composition in comparison with its B. jararaca
      relatives, which might represent an optimization of venom towards a specialized
      diet.

PMID- 16002344
TI  - Effects of selected xenoestrogens on liver peroxisomes, vitellogenin levels and
      spermatogenic cell proliferation in male zebrafish.
AB  - Environmental estrogenic compounds or xenoestrogens can mimic natural estrogens
      and cause a variety of adverse effects on aquatic wildlife. The purpose of the
      present work was to investigate if xenoestrogens are able to cause proliferation
      of liver peroxisomes using zebrafish (Danio rerio) as a model. Adult male
      zebrafish were exposed for 15 days to 17beta-estradiol (E2) and the xenoestrogens
      dibutylphthalate (DBP), methoxychlor (MXC), 4-tert-octylphenol (OP) and 17alpha
      ethynylestradiol (EE2). All five tested compounds caused significant
      proliferation of liver peroxisomes (p < 0.05) as indicated by increased
      peroxisomal surface and numerical densities and elevated activities of the
      peroxisomal beta-oxidation enzyme acyl-CoA oxidase (AOX). In the case of DBP, MXC
      and E2, positive significant correlations between peroxisomal density parameters
      and AOX were found. The treatments did not produce gross alterations in testis
      histology, but spermatogenic cell proliferation was disturbed in E2 and EE2
      treated groups and vitellogenin levels increased significantly in fish exposed to
      MXC, OP, EE2 and E2 with respect to controls. Furthermore, a significant
      correlation between vitellogenin levels and AOX activity was found for MXC, OP
      and EE2 treatments, suggesting that for the latter xenoestrogens early estrogenic
      effects are associated with liver peroxisome proliferation. No such association
      occurred with typical peroxisome proliferators such as DBP.

PMID- 16002345
TI  - Invariant aphthovirus consensus nucleotide sequence in the transition to error
      catastrophe.
AB  - RNA viruses replicate as complex distributions of non-identical but closely
      related variant genomes termed viral quasispecies. When the error rate during
      genome replication exceeds a threshold value, the genetic information cannot be
      maintained and the system enters error catastrophe. This violation of the error
      threshold results in virus extinction and it is currently being investigated as a
      new antiviral strategy, based on antiviral activity of some mutagenic agents.
      Previous studies with the important animal pathogen foot-and-mouth disease virus
      (FMDV) have shown that FMDV entry into error catastrophe is associated with an
      increase of complexity (mutation frequency and Shannon entropy) of the mutant
      spectrum of the quasispecies and that mutated, pre-extinction RNA interferes with
      the infectivity of standard RNA. Here, we report that despite the increase of
      complexity, the genomic consensus nucleotide sequence of pre-extinction FMDV RNA
      remains invariant, and that the fitness of pre-extinction FMDV is at least six
      fold lower than the fitness of the parental viral clone, prior to mutagenic
      treatments. Thus, a low fitness genome ensemble can suppress replication of high
      fitness virus. Furthermore, the results show that profound genetic modifications
      associated with fitness decrease of a virus population can take place without any
      manifestation in the consensus genomic sequence. Thus, increase in mutant
      spectrum complexity and invariance of the consensus sequence characterizes FMDV
      extinction through error catastrophe.

PMID- 16002347
TI  - Logistic trajectory maps and aerosol mixing due to asynchronous flow at airway
      bifurcations.
AB  - Aerosols too large for significant Brownian transport, and too small for
      significant inertial transport, are nonetheless known to deposit deep in the
      lung, and are associated with increased risk of pulmonary disease. Classical
      models fail to explain such transport. We hypothesized that kinematic
      irreversibility in ventilation, arising from velocity saddle-points or from flow
      asynchrony at airway bifurcations, may be the fundamental transport mechanism.
      Our experimental evidence shows striking trajectory irreversibility in rat lungs
      ventilated with 2-color polymerizable silicones, representing resident and tidal
      gas. The striated patterns in small airways, even after one ventilatory cycle,
      support our hypothesis. Here we analyze bifurcating flow asynchrony in a
      simplified one-dimensional model. We find: unexpected richness and chaos in
      particle trajectories; almost all trajectories visit all spatial positions;
      surprisingly, there is complete mixing-the limiting concentration is spatially
      uniform. This is a new finding supporting the idea that kinematic irreversibility
      is a potent mixing and transport mechanism for aerosols deep in the lung.

PMID- 16002346
TI  - Involvement of poly(ADP-ribose) polymerase activity in regulating Chk1-dependent
      apoptotic cell death.
AB  - The activity of poly(ADP-ribose) polymerase (PARP) is highly stimulated following
      DNA damage resulting in formation of DNA nicks and strand breaks. This leads to
      modification of numerous proteins, including itself, using NAD(+) as substrate
      and to exhaustion of intracellular ATP. A highly cytotoxic concentration of the
      DNA methylating agent methyl methanesulfonate (MMS) results in cellular ATP
      depletion and cell death primarily by necrosis in both wild-type and DNA
      polymerase beta null mouse fibroblasts. The loss of ATP can be prevented by the
      PARP inhibitor 4-amino-1,8-naphthalimide (4-AN), and now cells die by an energy
      dependent apoptotic pathway. We find that inhibition of PARP activity transforms
      a sub-lethal exposure to MMS into a highly cytotoxic event. Under this condition,
      ATP is not depleted and cell death is by apoptosis. The caspase inhibitor, Z-VAD,
      shifts the mechanism of cell death to necrosis indicating a caspase-dependent
      component of the apoptotic cell death. Co-exposure to the Chk1 inhibitor UCN-01
      also produces a decrease in apoptotic cell death, but now there is an increase in
      viable cells and an enhancement in long-term survival. Taken together, our
      results suggest that inhibition of PARP activity, induced as a result of low dose
      MMS exposure, signals via a Chk1-dependent pathway for cell death by apoptosis.

PMID- 16002348
TI  - HPLC determination of pirenzepine dihydrochloride in rabbit aqueous humor.
AB  - Pirenzepine was considered as a pharmacologic agent of preventing form
      deprivation myopia. To assess the ocular bioavailability of pirenzepine, a HPLC
      method for determination of pirenzepine in rabbit aqueous humor was developed. An
      HPLC system was used in the reverse phase mode for the determination of
      pirenzepine. A Luna RP18 5 microm 4.6 mm x 150 mm column was employed at 35
      degrees C. The mobile phase was methanol/0.02 M KH2PO4/sodium 1-pentanesulfonate
      (350/650/1, v/v/m, pH was adjusted to 8.0 by dropping 1M NaOH). The flow rate was
      1 ml/min. Pirenzepine was monitored at 280 nm. Sample treatment procedure
      consists of deproteinisation with methanol. Calibration curves fitted by plotting
      the peak area versus concentration were linear in the range 20-400 ng/ml. The
      limit of quantification (LOQ) of present method was 20 ng/ml. Within-day and
      inter-day coefficient of variation was lower than 10%. Analytical recoveries were
      determined as 92.4, 95.4 and 101.4% at concentrations of 40, 200 and 400 ng/ml.
      In conclusion, this HPLC method using a simple sample treatment procedure appears
      suitable for monitoring ocular concentration of pirenzepine.

PMID- 16002349
TI  - Separation and quantification of a novel two-component vaccine adjuvant.
AB  - Two reversed-phase HPLC methods were developed for the quantitative determination
      of the two components of the novel vaccine adjuvant IC31. The adjuvant consists
      of a mixture of a synthetic oligodeoxynucleotide (ODN) and an 11-mer cationic
      peptide. The negatively charged oligodeoxynucleotide and the positively charged
      peptide form a complex that has to be quantitatively dissociated for analysis.
      Dissociation of the complex was achieved with a basic heparin solution (1000
      IU/ml) when analyzing the ODN, whereas 30% acetic acid was used for the
      determination of the peptide. Both methods are suitable for identification and
      quantification but also for stability indicating investigations.

PMID- 16002350
TI  - Determination of DMF modified DNA base N4-methylcarbamoylcytosine in human urine
      using off-line sample clean-up, two-dimensional LC and ESI-MS/MS detection.
AB  - A sensitive internal standard method for the analysis of a DNA-adduct of N,N
      dimethylformamide (N4-methylcarbamoylcytosine, NMC-C) in human urine has been
      developed. A sample pre-treatment involving an acidic hydrolysis is followed by
      the sample clean-up performed with solid-phase extraction (SPE) technique using a
      cation-exchange resin. A two-dimensional liquid chromatography is used to
      separate the target analyte from the matrix using first a C18 reversed phase
      column with incorporated hydrophilic moieties and then a C8 bonded reversed phase
      column for the final separation. Quantification is carried out by positive
      electrospray ionisation and mass spectrometry detection of the transitions from
      molecule ions to product ions (169-->112 and 172-->115) for the analyte and the
      labelled internal standard, respectively. The detection limit in urine reaches
      down to 8 ng/L (48 pmol/L). In the general population NMC-C could not be
      detected. In 10 out of 32 urine samples of occupationally to DMF exposed subjects
      NMC-C could be detected. The concentrations ranged up to 172 ng/L (1023 pmol/L)
      with a 95th percentile of 121 ng/L (720 pmol/L).

PMID- 16002351
TI  - Quantitation of ibogaine and 12-hydroxyibogamine in human plasma by liquid
      chromatography with fluorimetric detection.
AB  - A high-performance liquid chromatographic (HPLC) method with fluorimetric
      detection was developed for the simultaneous determination of ibogaine and
      noribogaine in human plasma using fluorescein as internal standard. This method
      involved a solid phase extraction of the compounds from plasma using N
      vinylpyrrolidone-divinybenzene copolymer cartridges. Separation of the three
      analytes was performed on a reversed-phase Supelcosil C18 analytical column (75
      mm x 4.6mm i.d., 3 microm particle size). The excitation wavelength was set at
      230 nm for the first 15.8min and then at 440 nm for the following 14.2 min; the
      emission wavelength was set at 336 nm for the first 15.8 min and then at 514 nm
      for the following 14.2 min. Obtained from the method validation, inter-assay
      precision was 6.0-12.5% and accuracy was 95.4-104%. The extraction efficiencies
      of the assay were higher than 94% and were constant across the calibration range.
      The lower limits of quantitation were 0.89 ng/ml for ibogaine and 1 ng/ml for
      noribogaine; at these levels, precision was < or =17% and accuracy was 95-105%.
      In this paper, extensive stability testing was undertaken using a wide range of
      storage conditions. Special attention must be paid to sample handling to avoid
      light degradation of the compounds.

PMID- 16002352
TI  - Improving LC-MS sensitivity through increases in chromatographic performance:
      comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS.
AB  - Recent technological advances have made available reverse phase chromatographic
      media with a 1.7 microm particle size along with a liquid handling system that
      can operate such columns at much higher pressures. This technology, termed ultra
      performance liquid chromatography (UPLC), offers significant theoretical
      advantages in resolution, speed, and sensitivity for analytical determinations,
      particularly when coupled with mass spectrometers capable of high-speed
      acquisitions. This paper explores the differences in LC-MS performance by
      conducting a side-by-side comparison of UPLC for several methods previously
      optimized for HPLC-based separation and quantification of multiple analytes with
      maximum throughput. In general, UPLC produced significant improvements in method
      sensitivity, speed, and resolution. Sensitivity increases with UPLC, which were
      found to be analyte-dependent, were as large as 10-fold and improvements in
      method speed were as large as 5-fold under conditions of comparable peak
      separations. Improvements in chromatographic resolution with UPLC were apparent
      from generally narrower peak widths and from a separation of diastereomers not
      possible using HPLC. Overall, the improvements in LC-MS method sensitivity,
      speed, and resolution provided by UPLC show that further advances can be made in
      analytical methodology to add significant value to hypothesis-driven research.

PMID- 16002353
TI  - CARD15/NOD2 polymorphisms do not explain concordance of Crohn's disease in
      Swedish monozygotic twins.
AB  - BACKGROUND: CARD15/NOD2 polymorphisms are associated with Crohn's disease. There
      is a high concordance for disease and disease phenotype in monozygotic twin pairs
      with Crohn's disease. AIM: We studied CARD15/NOD2 polymorphisms in a Swedish,
      population-based cohort of monozygotic twins with Crohn's disease to assess
      whether these variants explain disease concordance. SUBJECTS AND METHODS: Twenty
      nine monozygotic twin pairs (concordant n=9, discordant n=20) with Crohn's
      disease and 192 healthy controls were investigated for the CARD15/NOD2 variants
      Arg702Trp, Gly908Arg and Leu1007fsinsC. RESULTS: CARD15/NOD2 mutations were found
      in 5/38 (13%) twins with Crohn's disease, corresponding to a total allele
      frequency of 6.6%. Only 2/9 concordant twin pairs carried any of the variants and
      the remaining seven were wild type genotype. The total allele frequency was 4.4
      times higher (95% confidence interval 1.0-21.5, p=0.06) in concordant twins than
      in discordant ones, 11.1% versus 2.5%. In healthy controls the total allele
      frequency was 2.6%. CONCLUSIONS: CARD15/NOD2 polymorphisms contribute but do not
      alone explain concordance of Crohn's disease in monozygotic twins and, at least
      in a Swedish population, other polymorphisms are required. The low occurrence of
      CARD15/NOD2 mutations in the study and other Northern European populations
      suggests that these variants are of less importance in Northern Europe.

PMID- 16002354
TI  - The internal capsule in neonatal imaging.
AB  - The internal capsule is highly visible on conventional magnetic resonance imaging
      (MRI). It is myelinating rapidly at term, and the time course of its maturation
      is well known. It carries the major motor and sensory pathways to and from the
      cortex and the spinal cord. Additionally, fibres from the thalamus pass through
      it connecting to most regions of the cortex. It is therefore of vital importance,
      and damage to it has severe consequences. Its abnormal appearance on conventional
      MRI is a good predictor of an abnormal motor outcome in different clinical
      situations encountered in perinatal medicine. Its normal appearance on
      conventional MR images at term age is usually associated with a relatively normal
      motor outcome. More recently, diffusion-weighted and diffusion tensor imaging
      have allowed a much more sophisticated assessment of its maturation and
      connectivity; this has already led to a better understanding of how its
      development is affected by preterm birth and by hypoxic-ischaemic brain injury.
      Future studies will assess the relevance of these findings not only for motor
      outcome but also for cognitive, visual and sensory abilities.

PMID- 16002355
TI  - Contaminant source zones: remediation or perpetual stewardship?

PMID- 16002356
TI  - The NIEHS and the National Toxicology Program: an integrated scientific vision.

PMID- 16002357
TI  - Urinary creatinine and arsenic metabolism.

PMID- 16002358
TI  - Ototoxicity.

PMID- 16002359
TI  - Bioremediation monitoring.

PMID- 16002360
TI  - The shape of food allergenicity.

PMID- 16002362
TI  - Paving paradise: the peril of impervious surfaces.

PMID- 16002363
TI  - Combined sewer systems: down, dirty, and out of date.

PMID- 16002364
TI  - Outsmarting olfaction: the next generation of mosquito repellents.

PMID- 16002366
TI  - Vinyl chloride: a case study of data suppression and misrepresentation.
AB  - When the U.S. Environmental Protection Agency (EPA) finalized its 2000 update of
      the toxicological effects of vinyl chloride (VC), it was concerned with two
      issues: the classification of VC as a carcinogen and the numerical estimate of
      its potency. In this commentary we describe how the U.S. EPA review of VC
      toxicology, which was drafted with substantial input from the chemical industry,
      weakened safeguards on both points. First, the assessment down-plays risks from
      all cancer sites other than the liver. Second, the estimate of cancer potency was
      reduced 10-fold from values previously used for environmental decision making, a
      finding that reduces the cost and extent of pollution reduction and cleanup
      measures. We suggest that this assessment reflects discredited scientific
      practices and recommend that the U.S. EPA reverse its trend toward ever
      increasing collaborations with the regulated industries when generating
      scientific reviews and risk assessments.

PMID- 16002367
TI  - Pesticide testing on human subjects: weighing benefits and risks.
AB  - In the debate surrounding testing pesticides on human subjects, two distinct
      positions have emerged. The first position holds that pesticide experiments on
      human subjects should be allowed, but only under stringent scientific and ethical
      standards. The second position asserts that these experiments should never be
      allowed. In this article, we evaluate what we consider to be the strongest
      argument for the second position--namely, that the benefits of the experiments
      are not significant enough to justify the risks posed to healthy subjects. We
      challenge this argument by examining the benefits and risks of testing pesticides
      on human subjects. We argue that a study that intentionally exposes humans
      subjects to pesticides should be permitted if a) the knowledge gained from the
      study is expected to promote human health; b) the knowledge cannot be reasonably
      obtained by other means; c) the study is not expected to cause serious or
      irreversible harm to the subjects; and d) appropriate safeguards are in place to
      minimize harm to the subjects.

PMID- 16002368
TI  - Ushering in the new toxicology: toxicogenomics and the public interest.
AB  - New scientific tools spawned by the genomics revolution promise to improve our
      ability to identify causative factors in human diseases. But as these new tools
      elucidate the complex interactions between chemical toxins and biologic systems,
      the strain on traditional ways of understanding toxic effects grows. Despite
      major advances in the science and technology of these new toxicogenomics tools,
      scientific and political complexities threaten to delay the use of toxicogenomics
      to further the public interest or--worse--to advance its use initially to weaken
      the regulation and safety of widely used chemicals. To gain further insight into
      the scientific and political landscape of the new toxicology, we interviewed 27
      experts from a variety of disciplines and sectors. Interviewees expressed
      widespread agreement that the new toxicology promises a significant increase in
      the amount of information available on toxic effects of chemicals. But the
      interviews show that the promise of the new toxicology will be realized only if
      technical and political obstacles can be overcome. Although scientific rigor is
      necessary for the new toxicology to move forward, the scientific and public
      interest communities must ensure that inappropriate definitions of rigor, as well
      as proprietary interests, do not create unnecessary barriers to more effective
      public health protection.

PMID- 16002370
TI  - Personalized exposure assessment: promising approaches for human environmental
      health research.
AB  - New technologies and methods for assessing human exposure to chemicals, dietary
      and lifestyle factors, infectious agents, and other stressors provide an
      opportunity to extend the range of human health investigations and advance our
      understanding of the relationship between environmental exposure and disease. An
      ad hoc Committee on Environmental Exposure Technology Development was convened to
      identify new technologies and methods for deriving personalized exposure
      measurements for application to environmental health studies. The committee
      identified a "toolbox" of methods for measuring external (environmental) and
      internal (biologic) exposure and assessing human behaviors that influence the
      likelihood of exposure to environmental agents. The methods use environmental
      sensors, geographic information systems, biologic sensors, toxicogenomics, and
      body burden (biologic) measurements. We discuss each of the methods in relation
      to current use in human health research; specific gaps in the development,
      validation, and application of the methods are highlighted. We also present a
      conceptual framework for moving these technologies into use and acceptance by the
      scientific community. The framework focuses on understanding complex human
      diseases using an integrated approach to exposure assessment to define particular
      exposure-disease relationships and the interaction of genetic and environmental
      factors in disease occurrence. Improved methods for exposure assessment will
      result in better means of monitoring and targeting intervention and prevention
      programs.

PMID- 16002369
TI  - Nanotoxicology: an emerging discipline evolving from studies of ultrafine
      particles.
AB  - Although humans have been exposed to airborne nanosized particles (NSPs; < 100
      nm) throughout their evolutionary stages, such exposure has increased
      dramatically over the last century due to anthropogenic sources. The rapidly
      developing field of nanotechnology is likely to become yet another source through
      inhalation, ingestion, skin uptake, and injection of engineered nanomaterials.
      Information about safety and potential hazards is urgently needed. Results of
      older biokinetic studies with NSPs and newer epidemiologic and toxicologic
      studies with airborne ultrafine particles can be viewed as the basis for the
      expanding field of nanotoxicology, which can be defined as safety evaluation of
      engineered nanostructures and nanodevices. Collectively, some emerging concepts
      of nanotoxicology can be identified from the results of these studies. When
      inhaled, specific sizes of NSPs are efficiently deposited by diffusional
      mechanisms in all regions of the respiratory tract. The small size facilitates
      uptake into cells and transcytosis across epithelial and endothelial cells into
      the blood and lymph circulation to reach potentially sensitive target sites such
      as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous
      system and ganglia via translocation along axons and dendrites of neurons has
      also been observed. NSPs penetrating the skin distribute via uptake into
      lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP
      surface chemistry (coating) and in vivo surface modifications. The greater
      surface area per mass compared with larger-sized particles of the same chemistry
      renders NSPs more active biologically. This activity includes a potential for
      inflammatory and pro-oxidant, but also antioxidant, activity, which can explain
      early findings showing mixed results in terms of toxicity of NSPs to
      environmentally relevant species. Evidence of mitochondrial distribution and
      oxidative stress response after NSP endocytosis points to a need for basic
      research on their interactions with subcellular structures. Additional
      considerations for assessing safety of engineered NSPs include careful selections
      of appropriate and relevant doses/concentrations, the likelihood of increased
      effects in a compromised organism, and also the benefits of possible desirable
      effects. An interdisciplinary team approach (e.g., toxicology, materials science,
      medicine, molecular biology, and bioinformatics, to name a few) is mandatory for
      nanotoxicology research to arrive at an appropriate risk assessment.

PMID- 16002371
TI  - Changes in levels of nerve growth factor in nasal secretions after capsaicin
      inhalation in patients with airway symptoms from scents and chemicals.
AB  - Patients complaining of upper and lower airway symptoms caused by scents and
      chemicals have previously been shown to have increased cough sensitivity to
      inhaled capsaicin, but the precise mechanisms behind this reaction are unknown.
      Hypothesizing that a neurochemical alteration related to sensory hyperreactivity
      (SHR) of the airway mucosa occurs, we measured levels of nerve growth factor
      (NGF) in nasal lavage fluid (NAL) before and after capsaicin inhalation
      provocations and related the capsaicin cough sensitivity to the NGF levels.
      Thirteen patients with SHR and 14 control subjects were provoked with capsaicin
      inhalation at three different doses. We measured NGF in NAL before and after
      provocation and recorded cough and capsaicin-induced symptoms. All subjects
      demonstrated a dose-dependent cough response to capsaicin inhalation, with a more
      pronounced effect in patients than in controls. Basal levels of NGF were
      significantly lower in the patient group than in the control subjects (p < 0.01).
      After capsaicin provocation, the patients showed a significant increase in NGF (p
      < 0.01), which was related to capsaicin cough sensitivity. The findings
      demonstrate that, in patients with airway symptoms induced by scents and
      chemicals, SHR is real and measurable, demonstrating a pathophysiology in the
      airways of these patients compared to healthy subjects.

PMID- 16002372
TI  - Lipid adjustment in the analysis of environmental contaminants and human health
      risks.
AB  - The literature on exposure to lipophilic agents such as polychlorinated biphenyls
      (PCBs) is conflicting, posing challenges for the interpretation of potential
      human health risks. Laboratory variation in quantifying PCBs may account for some
      of the conflicting study results. For example, for quantification purposes, blood
      is often used as a proxy for adipose tissue, which makes it necessary to model
      serum lipids when assessing health risks of PCBs. Using a simulation study, we
      evaluated four statistical models (unadjusted, standardized, adjusted, and two
      stage) for the analysis of PCB exposure, serum lipids, and health outcome risk
      (breast cancer). We applied eight candidate true causal scenarios, depicted by
      directed acyclic graphs, to illustrate the ramifications of misspecification of
      underlying assumptions when interpreting results. Statistical models that
      deviated from underlying causal assumptions generated biased results. Lipid
      standardization, or the division of serum concentrations by serum lipids, was
      observed to be highly prone to bias. We conclude that investigators must consider
      biology, biologic medium (e.g., nonfasting blood samples), laboratory
      measurement, and other underlying modeling assumptions when devising a
      statistical plan for assessing health outcomes in relation to environmental
      exposures.

PMID- 16002373
TI  - Serum dioxin concentrations and age at menopause.
AB  - 2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the
      aryl hydrocarbon receptor, is a by-product of numerous industrial processes
      including waste incineration. Studies in rats and monkeys suggest that TCDD may
      affect ovarian function. We examined the relationship of TCDD and age at
      menopause in a population of women residing near Seveso, Italy, in 1976, at the
      time of a chemical plant explosion. We included 616 of the women who participated
      20 years later in the Seveso Women's Health Study. All women were premenopausal
      at the time of the explosion, had TCDD levels measured in serum collected soon
      after the explosion, and were > or = 35 years of age at interview. Using
      proportional hazards modeling, we found a 6% nonsignificant increase in risk of
      early menopause with a 10-fold increase in serum TCDD. When TCDD levels were
      categorized, compared with women in the lowest quintile (< 20.4 ppt), women in
      quintile 2 (20.4-34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3
      (34.3-54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2-118 ppt) had an HR
      of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for
      risk of earlier menopause. The trend toward earlier menopause across the first
      four quintiles is statistically significant (p = 0.04). These results suggest a
      nonmonotonic dose-related association with increasing risk of earlier menopause
      up to about 100 ppt TCDD, but not above.

PMID- 16002374
TI  - Influence of tap water quality and household water use activities on indoor air
      and internal dose levels of trihalomethanes.
AB  - Individual exposure to trihalomethanes (THMs) in tap water can occur through
      ingestion, inhalation, or dermal exposure. Studies indicate that activities
      associated with inhaled or dermal exposure routes result in a greater increase in
      blood THM concentration than does ingestion. We measured blood and exhaled air
      concentrations of THM as biomarkers of exposure to participants conducting 14
      common household water use activities, including ingestion of hot and cold tap
      water beverages, showering, clothes washing, hand washing, bathing, dish washing,
      and indirect shower exposure. We conducted our study at a single residence in
      each of two water utility service areas, one with relatively high and the other
      low total THM in the residence tap water. To maintain a consistent exposure
      environment for seven participants, we controlled water use activities, exposure
      time, air exchange, water flow and temperature, and nonstudy THM sources to the
      indoor air. We collected reference samples for water supply and air (pre-water
      use activity), as well as tap water and ambient air samples. We collected blood
      samples before and after each activity and exhaled breath samples at baseline and
      post-activity. All hot water use activities yielded a 2-fold increase in blood or
      breath THM concentrations for at least one individual. The greatest observed
      increase in blood and exhaled breath THM concentration in any participant was due
      to showering (direct and indirect), bathing, and hand dishwashing. Average
      increase in blood THM concentration ranged from 57 to 358 pg/mL due to these
      activities. More research is needed to determine whether acute and frequent
      exposures to THM at these concentrations have public health implications. Further
      research is also needed in designing epidemiologic studies that minimize data
      collection burden yet maximize accuracy in classification of dermal and
      inhalation THM exposure during hot water use activities.

PMID- 16002375
TI  - Polychlorinated biphenyls disturb differentiation of normal human neural
      progenitor cells: clue for involvement of thyroid hormone receptors.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous environmental chemicals that
      accumulate in adipose tissues over the food chain. Epidemiologic studies have
      indicated that PCBs influence brain development. Children who are exposed to PCBs
      during development suffer from neuropsychologic deficits such as a lower full
      scale IQ (intelligence quotient), reduced visual recognition memory, and
      attention and motor deficits. The mechanisms leading to these effects are not
      fully understood. It has been speculated that PCBs may affect brain development
      by interfering with thyroid hormone (TH) signaling. Because most of the data are
      from animal studies, we established a model using primary normal human neural
      progenitor (NHNP) cells to determine if PCBs interfere with TH-dependent neural
      differentiation. NHNP cells differentiate into neurons, astrocytes, and
      oligodendrocytes in culture, and they express a variety of drug metabolism
      enzymes and nuclear receptors. Like triiodothyronine (T3), treatment with the
      mono-ortho-substituted PCB-118 (2,3',4,4 ,5-pentachlorobiphenyl; 0.01-1 microM)
      leads to a dose-dependent increase of oligodendrocyte formation. This effect was
      congener specific, because the coplanar PCB-126 (3,3',4,4 ,5-pentachlorobiphenyl)
      had no effect. Similar to the T3 response, the PCB-mediated effect on
      oligodendrocyte formation was blocked by retinoic acid and the thyroid hormone
      receptor antagonist NH-3. These results suggest that PCB-118 mimics T3 action via
      the TH pathway.

PMID- 16002376
TI  - Neurologic symptoms in licensed private pesticide applicators in the agricultural
      health study.
AB  - Exposure to high levels of many pesticides has both acute and long-term
      neurologic consequences, but little is known about the neurotoxicity of chronic
      exposure to moderate levels of pesticides. We analyzed cross-sectional data from
      18,782 white male licensed private pesticide applicators enrolled in the
      Agricultural Health Study in 1993-1997. Applicators provided information on
      lifetime pesticide use and 23 neurologic symptoms typically associated with
      pesticide intoxication. An indicator of more symptoms (> or = 10 vs. < 10) during
      the year before enrollment was associated with cumulative lifetime days of
      insecticide use: odds ratios (95% confidence intervals) were 1.64 (1.36-1.97) for
      1-50 days, 1.89 (1.58-2.25) for 51-500 days, and 2.50 (2.00-3.13) for > 500 days,
      compared with never users. A modest association for fumigants [> 50 days, 1.50
      (1.24-1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99
      1.75)] and fungicides [> 50 days, 1.23 (1.00-1.50)] were observed. Pesticide use
      within the year before enrollment was not associated with symptom count. Only
      associations with insecticides and fumigants persisted when all four pesticide
      groups were examined simultaneously. Among chemical classes of insecticides,
      associations were strongest for organophosphates and organochlorines.
      Associations with cumulative exposure persisted after excluding individuals who
      had a history of pesticide poisoning or had experienced an event involving high
      personal pesticide exposure. These results suggest that self-reported neurologic
      symptoms are associated with cumulative exposure to moderate levels of fumigants
      and organophosphate and organochlorine insecticides, regardless of recent
      exposure or history of poisoning.

PMID- 16002377
TI  - Air pollution and ST-segment depression in elderly subjects.
AB  - Increased levels of daily ambient particle pollution have been associated with
      increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the
      traffic-related component of particles. We investigated associations between
      ambient pollution and ST-segment levels in a repeated-measures study including
      269 observations on 24 active Boston residents 61-88 years of age, each observed
      up to 12 times from June through September 1999. The protocol involved continuous
      Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5
      min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing.
      Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile
      change in BC. We calculated the average ST-segment level, referenced to the P-R
      isoelectric values, for each portion of the protocol. The mean BC level in the
      previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment
      depression in most portions of the protocol, but the effect was strongest in the
      postexercise periods. During postexercise rest, an elevated BC level was
      associated with -0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p =
      0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased
      risk of ST-segment depression > or = 0.5 mm among those with at least one episode
      of that level of ST-segment depression. Carbon monoxide was not a confounder of
      this association. ST-segment depression, possibly representing myocardial
      ischemia or inflammation, is associated with increased exposure to particles
      whose predominant source is traffic.

PMID- 16002378
TI  - Grand rounds: latex-induced occupational asthma in a surgical pathologist.
AB  - CONTEXT: Latex allergy and sensitization have been an important problem facing
      health care workers. Providing a latex-safe environment is the intervention of
      choice. CASE PRESENTATION: A 46-year-old surgical pathologist presented with
      increasing shortness of breath for the previous 4 years. Twenty years before
      presentation, he noted a pruritic, erythematous rash on his hands, associated
      with latex glove use. Fourteen years before presentation, during pathology
      residency, he developed a nonproductive cough, wheezing, and an urticarial rash,
      temporally associated with use of powdered latex gloves. These symptoms improved
      while away from work. At presentation, he had one-flight dyspnea. His skin prick
      test was positive for latex, and pulmonary function testing showed mild
      obstruction, which was reversible with bronchodilator use. Because the patient
      was at risk for worsening pulmonary function and possible anaphylaxis with
      continued exposure, he was removed from the workplace because no reasonable
      accommodation was made for him at that time. DISCUSSION: The patient's
      presentation is consistent with latex-induced occupational asthma. Initially
      noting dermal manifestations, consistent with an allergic contact dermatitis
      secondary to accelerators present in latex gloves, he later developed urticaria,
      flushing, and respiratory symptoms, consistent with a type I hypersensitivity
      reaction to latex. He also has reversible airways disease, with significant
      improvement of peak expiratory flow rate and symptoms when away from work.
      RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: The ideal treatment for latex
      sensitization is removal from and avoidance of exposure. Clinicians should
      consider occupational asthma when patients present with new-onset asthma or
      asthmatic symptoms that worsen at work.

PMID- 16002379
TI  - Low-level environmental lead exposure and children's intellectual function: an
      international pooled analysis.
AB  - Lead is a confirmed neurotoxin, but questions remain about lead-associated
      intellectual deficits at blood lead levels < 10 microg/dL and whether lower
      exposures are, for a given change in exposure, associated with greater deficits.
      The objective of this study was to examine the association of intelligence test
      scores and blood lead concentration, especially for children who had maximal
      measured blood lead levels < 10 microg/dL. We examined data collected from 1,333
      children who participated in seven international population-based longitudinal
      cohort studies, followed from birth or infancy until 5-10 years of age. The full
      scale IQ score was the primary outcome measure. The geometric mean blood lead
      concentration of the children peaked at 17.8 microg/dL and declined to 9.4
      microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead
      concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration
      < 7.5 microg/dL. After adjustment for covariates, we found an inverse
      relationship between blood lead concentration and IQ score. Using a log-linear
      model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4]
      associated with an increase in concurrent blood lead levels from 2.4 to 30
      microg/dL. The estimated IQ point decrements associated with an increase in blood
      lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were
      3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5),
      respectively. For a given increase in blood lead, the lead-associated
      intellectual decrement for children with a maximal blood lead level < 7.5
      microg/dL was significantly greater than that observed for those with a maximal
      blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental
      lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is
      associated with intellectual deficits.

PMID- 16002380
TI  - Blood lead level and risk of asthma.
AB  - Asthma and lead poisoning are prevalent among urban children in the United
      States. Lead exposure may be associated with excessive production of
      immunoglobulin E, possibly increasing asthma risk and contributing to racial
      disparities. The objective of this study was to examine racial differences in the
      association of blood lead level (BLL) to risk of developing asthma. We
      established and followed a cohort prospectively to determine asthma onset, using
      patient encounters and drug claims obtained from hospital databases. Participants
      were managed care enrollees with BLL measured and documented at 1-3 years of age.
      We used multiple variable analysis techniques to determine the relationship of
      BLL to period prevalent and incident asthma. Of the 4,634 children screened for
      lead from 1995 through 1998, 69.5% were African American, 50.5% were male, and
      mean age was 1.2 years. Among African Americans, BLL > or = 5 and BLL > or = 10
      microg/dL were not associated with asthma. The association of BLL > or = 5
      microg/dL with asthma among Caucasians was slightly elevated, but not significant
      [adjusted hazard ratio (adjHR) = 1.4; 95% confidence interval (CI), 0.7-2.9; p =
      0.40]. Despite the small number of Caucasians with high BLL, the adjHR increased
      to 2.7 (95% CI, 0.9-8.1; p = 0.09) when more stringent criteria for asthma were
      used. When compared with Caucasians with BLL < 5 microg/dL, African Americans
      were at a significantly increased risk of asthma regardless of BLL (adjHR = 1.4
      3.0). We conclude that an effect of BLL on risk of asthma for African Americans
      was not observed. These results demonstrate the need for further exploration of
      the complex interrelationships between race, asthma phenotype, genetic
      susceptibilities, and socioenvironmental exposures, including lead.

PMID- 16002381
TI  - Umbilical cord mercury concentration as biomarker of prenatal exposure to
      methylmercury.
AB  - Biomarkers are often applied to assess prenatal exposure to methylmercury in
      research and surveillance. In a prospective study in the Faroe Islands, the main
      exposure biomarkers were the mercury concentrations in cord blood and maternal
      hair obtained at parturition. We have now supplemented these exposure biomarkers
      with mercury analyses of umbilical cord tissue from 447 births. In particular,
      when expressed in relation to the dry weight of the tissue, the cord mercury
      concentration correlated very well with that in cord blood. Structural equation
      model analysis showed that these two biomarkers have average total imprecision of
      about 30%, which is much higher than the laboratory error. The imprecision of the
      dry-weight-based concentration was lower than that of the wet-weight-based
      parameter, and it was intermediate between those of the cord blood and the hair
      biomarkers. In agreement with this finding, regression analyses showed that the
      dry-weight cord mercury concentration was almost as good a predictor of
      methylmercury-associated neuropsychologic deficits at 7 years of age as was the
      cord-blood mercury concentration. Cord mercury analysis can therefore be used as
      a valid measure of prenatal methylmercury exposure, but appropriate adjustment
      for the imprecision should be considered.

PMID- 16002382
TI  - Risk of brain tumors in children and susceptibility to organophosphorus
      insecticides: the potential role of paraoxonase (PON1).
AB  - Prior research suggests that childhood brain tumors (CBTs) may be associated with
      exposure to pesticides. Organophosphorus insecticides (OPs) target the developing
      nervous system, and until recently, the most common residential insecticides were
      chlorpyrifos and diazinon, two OPs metabolized in the body through the cytochrome
      P450/paraoxonase 1 (PON1) pathway. To investigate whether two common PON1
      polymorphisms, C-108T and Q192R, are associated with CBT occurrence, we conducted
      a population-based study of 66 cases and 236 controls using DNA from neonatal
      screening archive specimens in Washington State, linked to interview data. The
      risk of CBT was nonsignificantly increased in relation to the inefficient PON1
      promoter allele [per PON1(-108T) allele, relative to PON1(-108CC): odds ratio
      (OR) = 1.4; 95% confidence interval (CI), 1.0-2.2; p-value for trend = 0.07].
      Notably, this association was strongest and statistically significant among
      children whose mothers reported chemical treatment of the home for pests during
      pregnancy or childhood (per PON1(-108T) allele: among exposed, OR = 2.6; 95% CI,
      1.2-5.5; among unexposed, OR = 0.9; 95% CI, 0.5-1.6) and for primitive
      neuroectodermal tumors (per PON1(-108T) allele: OR = 2.4; 95% CI, 1.1-5.4). The
      Q192R polymorphism, which alters the structure of PON1 and influences enzyme
      activity in a substrate-dependent manner, was not associated with CBT risk, nor
      was the PON1(C-108T/Q192R) haplotype. These results are consistent with an
      inverse association between PON1 levels and CBT occurrence, perhaps because of
      PON1's ability to detoxify OPs common in children's environments. Larger studies
      that measure plasma PON1 levels and incorporate more accurate estimates of
      pesticide exposure will be required to confirm these observations.

PMID- 16002393
TI  - Diagnostic value of measuring Epstein-Barr virus (EBV) DNA load and carcinoma
      specific viral mRNA in relation to anti-EBV immunoglobulin A (IgA) and IgG
      antibody levels in blood of nasopharyngeal carcinoma patients from Indonesia.
AB  - Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and is
      strongly associated with Epstein-Barr virus (EBV). We investigated the primary
      diagnostic value of circulating EBV DNA and anti-EBV immunoglobulin G (IgG) and
      IgA levels in Indonesian NPC patients (n = 149). By a 213-bp Epstein-Barr virus
      nuclear antigen 1 (EBNA1)-based real-time LightCycler PCR, 72.5% of patients were
      positive for EBV DNA in whole blood, with 29.5% having levels above a previously
      determined clinical cutoff value (COV) of 2,000 EBV DNA copies/ml, the upper
      level in healthy carriers. In a 99-bp LightCycler PCR, 85.9% of patients were
      positive and 60.4% had levels above the COV. This assay quantified a
      significantly higher EBV load than the 213-bp PCR assay (P < 0.0001), suggesting
      that circulating EBV DNA is fragmented. Using data from 11 different studies, we
      showed a significant inverse correlation between PCR amplicon size and the
      percentage of patients positive for circulating EBV DNA (Spearman's rho = -0.91;
      P < 0.0001). EBV DNA loads were unrelated to anti-EBV IgG or IgA levels, as
      measured by VCA-p18 and EBNA1-specific synthetic peptide-based enzyme-linked
      immunosorbent assays. The presence of circulating tumor cells was assessed by
      amplification of BamHI-A rightward frame 1 (BARF1) mRNA, a viral oncogene
      abundantly expressed in EBV-carrying carcinomas but virtually absent from EBV
      associated lymphomas. Despite high EBV DNA loads and the presence of EBNA1 and
      human U1A small nuclear ribonucleoprotein mRNA, BARF1 mRNA was never detected in
      blood. We conclude that amplicon size significantly influences EBV DNA load
      measurement in NPC patients. The circulating EBV DNA load is independent of
      serological parameters and does not reflect intact tumor cells. The primary
      diagnostic value of the EBV DNA load for the detection of NPC is limited.

PMID- 16002395
TI  - Microtubule-independent and protein kinase A-mediated function of kinesin KIF17b
      controls the intracellular transport of activator of CREM in testis (ACT).
AB  - Kinesins are motor proteins that transport their cargos along microtubules in an
      ATP-dependent manner. The testis-specific kinesin KIF17b was shown to directly
      regulate cAMP-response element modulator (CREM)-dependent transcription by
      determining the subcellular localization of the activator of CREM in testis
      (ACT), the testis-specific coactivator of CREM in postmeiotic male germ cells.
      CREM is a crucial transcriptional regulator of many important genes required for
      spermatid maturation, as demonstrated by the complete block of sperm development
      at the first steps of spermiogenesis in crem-null mice. To better understand the
      complex regulation of postmeiotic germ cell differentiation, we further
      characterized the ACT-KIF17b interaction, the function of KIF17b, and the
      signaling pathways governing its action. In this study, we demonstrated that the
      abilities of KIF17b to shuttle between the nuclear and the cytoplasmic
      compartments and to transport ACT are neither dependent on its motor domain nor
      on microtubules, thus revealing a novel microtubule-independent function for
      kinesins. We also showed that the cyclic AMP-dependent protein kinase A mediates
      the phosphorylation of KIF17b, and this modification is important for its
      subcellular localization. These results indicate that cyclic AMP signaling
      controls CREM-mediated transcription in male germ cells through modification of
      KIF17b function.

PMID- 16002394
TI  - A novel mechanism for adenylyl cyclase inhibition from the crystal structure of
      its complex with catechol estrogen.
AB  - Catechol estrogens are steroid metabolites that elicit physiological responses
      through binding to a variety of cellular targets. We show here that catechol
      estrogens directly inhibit soluble adenylyl cyclases and the abundant trans
      membrane adenylyl cyclases. Catechol estrogen inhibition is non-competitive with
      respect to the substrate ATP, and we solved the crystal structure of a catechol
      estrogen bound to a soluble adenylyl cyclase from Spirulina platensis in complex
      with a substrate analog. The catechol estrogen is bound to a newly identified,
      conserved hydrophobic patch near the active center but distinct from the ATP
      binding cleft. Inhibitor binding leads to a chelating interaction between the
      catechol estrogen hydroxyl groups and the catalytic magnesium ion, distorting the
      active site and trapping the enzyme substrate complex in a non-productive
      conformation. This novel inhibition mechanism likely applies to other adenylyl
      cyclase inhibitors, and the identified ligand-binding site has important
      implications for the development of specific adenylyl cyclase inhibitors.

PMID- 16002396
TI  - Molecular organization of target of rapamycin complex 2.
AB  - The target of rapamycin (TOR), a highly conserved serine/threonine kinase, plays
      a central role in the control of eukaryotic cell growth. TOR exists in two
      functionally and structurally distinct complexes, TOR complex 1 (TORC1) and TOR
      complex 2 (TORC2). TORC1 controls cell growth via a rapamycin-sensitive signaling
      branch regulating translation, transcription, nutrient uptake, ribosome
      biogenesis, and autophagy. TORC2 controls the organization of the actin
      cytoskeleton through a rapamycin-insensitive signaling branch and in yeast
      consists of the six proteins AVO1, AVO2, AVO3, BIT61, LST8, and TOR2. Here we
      have focused on the characterization of TORC2. Our studies suggest that TORC2 is
      oligomeric, likely a TORC2-TORC2 dimer. AVO1 and AVO3 bind cooperatively to the N
      terminal HEAT repeat region in TOR2 and are required for TORC2 integrity. AVO2 is
      a nonessential peripheral protein associated with AVO1 and AVO3. LST8 binds
      separately to the C-terminal kinase domain region in TOR2 and appears to modulate
      both the integrity and kinase activity of TORC2. TORC2 autophosphorylates sites
      in AVO1 and AVO3, but TORC2 kinase activity is not required for TORC2 integrity.
      We have demonstrated that mammalian TOR is also oligomeric. The architecture of
      TORC2 is discussed in the context of TORC2 assembly and regulation.

PMID- 16002398
TI  - Proteomic analysis of rhoptry organelles reveals many novel constituents for host
      parasite interactions in Toxoplasma gondii.
AB  - Rhoptries are specialized secretory organelles that are uniquely present within
      protozoan parasites of the phylum Apicomplexa. These obligate intracellular
      parasites comprise some of the most important parasites of humans and animals,
      including the causative agents of malaria (Plasmodium spp.) and chicken
      coccidiosis (Eimeria spp.). The contents of the rhoptries are released into the
      nascent parasitophorous vacuole during invasion into the host cell, and the
      resulting proteins often represent the literal interface between host and
      pathogen. We have developed a method for highly efficient purification of
      rhoptries from one of the best studied Apicomplexa, Toxoplasma gondii, and we
      carried out a detailed proteomic analysis using mass spectrometry that has
      identified 38 novel proteins. To confirm their rhoptry origin, antibodies were
      raised to synthetic peptides and/or recombinant protein. Eleven of 12 of these
      yielded antibody that showed strong rhoptry staining by immunofluorescence within
      the rhoptry necks and/or their bulbous base. Hemagglutinin epitope tagging
      confirmed one additional novel protein as from the rhoptry bulb. Previously
      identified rhoptry proteins from Toxoplasma and Plasmodium were unique to one or
      the other organism, but our elucidation of the Toxoplasma rhoptry proteome
      revealed homologues that are common to both. This study also identified the first
      Toxoplasma genes encoding rhoptry neck proteins, which we named RONs,
      demonstrated that toxofilin and Rab11 are rhoptry proteins, and identified novel
      kinases, phosphatases, and proteases that are likely to play a key role in the
      ability of the parasite to invade and co-opt the host cell for its own survival
      and growth.

PMID- 16002399
TI  - Interactions among yeast protein-disulfide isomerase proteins and endoplasmic
      reticulum chaperone proteins influence their activities.
AB  - We previously reported that the reductive activities of yeast protein-disulfide
      isomerase (PDI) family proteins did not completely explain their contribution to
      the viability of Saccharomyces cerevisiae (Kimura, T., Hosoda, Y., Kitamura, Y.,
      Nakamura, H., Horibe, T., and Kikuchi, M. (2004) Biochem. Biophys. Res. Commun.
      320, 359-365). In this study, we examined oxidative refolding activities and
      found that Mpd1p, Mpd2, and Eug1p exhibit activities of 13.8, 16.0, and 2.16%,
      respectively, compared with Pdi1p and that activity for Eps1p is undetectable. In
      analyses of interactions between yeast PDI proteins and endoplasmic reticulum
      molecular chaperones, we found that Mpd1p alone does not have chaperone activity
      but that it interacts with and inhibits the chaperone activity of Cne1p, a
      homologue of mammalian calnexin, and that Cne1p increases the reductive activity
      of Mpd1p. These results suggest that the interface between Mpd1p and Cne1p is
      near the peptide-binding site of Cne1p. In addition, Eps1p interacts with Pdi1p,
      Eug1p, Mpd1p, and Kar2p with dissociation constants (KD) in the range of 10(-7)
      to 10(-6). Interestingly, co-chaperone activities were completely suppressed in
      Eps1p-Pdi1p and Eps1p-Mpd1p complexes, although only Eps1p and Pdi1p have
      chaperone activity. The in vivo consequences of these results are discussed.

PMID- 16002397
TI  - The opportunistic pathogen Toxoplasma gondii deploys a diverse legion of invasion
      and survival proteins.
AB  - Host cell invasion is an essential step during infection by Toxoplasma gondii, an
      intracellular protozoan that causes the severe opportunistic disease
      toxoplasmosis in humans. Recent evidence strongly suggests that proteins
      discharged from Toxoplasma apical secretory organelles (micronemes, dense
      granules, and rhoptries) play key roles in host cell invasion and survival during
      infection. However, to date, only a limited number of secretory proteins have
      been discovered, and the full spectrum of effector molecules involved in parasite
      invasion and survival remains unknown. To address these issues, we analyzed a
      large cohort of freely released Toxoplasma secretory proteins by using two
      complementary methodologies, two-dimensional electrophoresis/mass spectrometry
      and liquid chromatography/electrospray ionization-tandem mass spectrometry
      (MudPIT, shotgun proteomics). Visualization of Toxoplasma secretory products by
      two-dimensional electrophoresis revealed approximately 100 spots, most of which
      were successfully identified by protein microsequencing or matrix-assisted laser
      desorption ionization-mass spectrometry analysis. Many proteins were present in
      multiple species suggesting they are subjected to substantial post-translational
      modification. Shotgun proteomic analysis of the secretory fraction revealed
      several additional products, including novel putative adhesive proteins,
      proteases, and hypothetical secretory proteins similar to products expressed by
      other related parasites including Plasmodium, the etiologic agent of malaria. A
      subset of novel proteins were re-expressed as fusions to yellow fluorescent
      protein, and this initial screen revealed shared and distinct localizations
      within secretory compartments of T. gondii tachyzoites. These findings provided a
      uniquely broad view of Toxoplasma secretory proteins that participate in parasite
      survival and pathogenesis during infection.

PMID- 16002400
TI  - Beta-amyloid-induced dynamin 1 depletion in hippocampal neurons. A potential
      mechanism for early cognitive decline in Alzheimer disease.
AB  - Synaptic dysfunction is one of the earliest events in the pathogenesis of
      Alzheimer disease (AD). However, the molecular mechanisms underlying synaptic
      defects in AD are largely unknown. We report here that beta-amyloid (Abeta), the
      main component of senile plaques, induced a significant decrease in dynamin 1, a
      protein that is essential for synaptic vesicle recycling and, hence, for memory
      formation and information processing. The Abeta-induced dynamin 1 decrease
      occurred in the absence of overt synaptic loss and was also observed in the
      Tg2576 mouse model of AD. In addition, our results provided evidence that the
      Abeta-induced decrease in dynamin 1 was likely the result of a calpain-mediated
      cleavage of dynamin 1 protein and possibly the down-regulation of dynamin 1 gene
      expression. These data suggest a mechanism to explain the early cognitive loss
      without a major decline in synapse number observed in AD and propose a novel
      therapeutic target for AD intervention.

PMID- 16002401
TI  - Regulation of p21-activated kinase-independent Rac1 signal transduction by
      nischarin.
AB  - Nischarin regulates Rac1-dependent cell motility by interaction with and
      inhibition of the p21-activated kinase (PAK1). In addition to regulating the
      activation of PAK1, Rac1 controls multiple downstream pathways to regulate cell
      growth and differentiation, as well as cell motility. Signaling by a
      constitutively activated Rac1 mutant deficient in PAK binding (Rac1Q61L-40C) was
      examined to determine whether Nischarin impinges on these other Rac1 effector
      pathways. Nischarin formed immunoprecipitatable complexes with Rac1Q61L and
      Rac1Q61L-40C when the proteins were co-expressed. In NIH3T3 cells, Rac1Q61L and
      Rac1Q61L-40C stimulation of a minimal NF-kappaB response element or the cyclin D1
      promoter, a downstream target of NF-kappaB, was inhibited by co-expression of
      Nischarin. Additionally, suppression of endogenous Nischarin protein with small
      interfering RNA in PC12 cells enhanced Rac1Q61L and Rac1Q61L-40C activation of NF
      kappaB. In further support of Nischarin suppressing PAK independent Rac
      signaling, foci formation in monolayers of NIH3T3 cells by Rac1Q61L-40C in
      cooperation with c-Raf/CAAX was inhibited by the presence of Nischarin. Nischarin
      alters the cellular localization of Rac1Q61L and Rac1Q61L-40C to vesicles and
      this positively correlates with the repression of the Rac1 signal. Thus,
      Nischarin, in addition to regulating the PAK strand of Rac1 signaling, can also
      regulate other links in the web of Rac1 signaling pathways.

PMID- 16002402
TI  - The Groucho-related gene family regulates the gonadotropin-releasing hormone gene
      through interaction with the homeodomain proteins MSX1 and OCT1.
AB  - Gonadotropin-releasing hormone (GnRH) is exclusively expressed in a unique
      population of hypothalamic neurons that controls reproductive function. GnRH gene
      expression is highly dynamic. Its transcriptional activity is regulated in a
      complex spatiotemporal manner during embryonic development and postnatal life.
      Although a variety of transcription factors have been identified as regulators of
      GnRH transcription, most are promiscuous in their DNA-binding requirements, and
      none are solely expressed in GnRH neurons. Their specific activity is probably
      determined by interactions with distinct cofactors. Here we find that the Groucho
      related gene (GRG) family of co-repressors is expressed in a model cell line for
      the GnRH neuron and co-expresses with GnRH during prenatal development. GRG
      proteins associate in vivo with the GnRH promoter. Furthermore, GRG proteins
      interact with two regulators of GnRH transcription, the homeodomain proteins MSX1
      and OCT1. Co-transfection experiments indicate that GRG proteins regulate GnRH
      promoter activity. The long GRG forms enhance MSX1 repression and counteract OCT1
      activation of the GnRH gene. In contrast, the short form, GRG5, has a dominant
      negative effect on MSX1-dependent repression. Taken together, these data suggest
      that the dynamic switch between activation and repression of GnRH transcription
      is mediated by recruitment of the GRG co-regulators.

PMID- 16002403
TI  - Localized Na+/H+ exchanger 1 expression protects Ca2+-regulated adenylyl cyclases
      from changes in intracellular pH.
AB  - The Ca2+-sensitive adenylyl cyclases (ACs) are exclusively regulated by
      capacitative Ca2+ entry (CCE) in nonexcitable cells. The present study
      investigates whether this Ca2+-dependent modulation of AC activity is further
      regulated by local pH changes that can arise beneath the plasma membrane as a
      consequence of cellular activity. Ca2+ stimulation of AC8 expressed in HEK 293
      cells and inhibition of endogenous AC6 in C6-2B glioma cells exhibited clear
      sensitivity to modest pH changes in vitro. Acid pH (pH 7.14) reduced the Ca2+
      sensitivity of both ACs, whereas alkaline pH (pH 7.85) enhanced the
      responsiveness of the enzymes to Ca2+, compared with controls (pH 7.50).
      Surprisingly, in the intact cell, the response of AC8 and AC6 to CCE was largely
      unperturbed by similar changes in intracellular pH (pH(i)), imposed using a weak
      acid (propionate) or weak base (trimethylamine). A range of hypotheses were
      tested to identify the mechanism(s) that could underlie this lack of pH effect in
      the intact cell. The pH sensitivity of CCE in HEK 293 cells is likely to dampen
      the effects of pH(i) on Ca2+-regulated ACs and may partly explain the discrepancy
      between in vitro and in vivo data. However, we have found that the Na+/H+
      exchanger (NHE), NHE1, is functionally active in these cells, and like AC8 (and
      AC6) it resides in lipid rafts or caveolae, which may create cellular
      microdomains where pH(i) is tightly regulated. An abundance of NHE1 in these
      cellular subdomains may generate a privileged environment that protects the Ca2+
      sensitive ACs and other caveolar proteins from local acid shifts.

PMID- 16002404
TI  - Preponderance of free mediator in the yeast Saccharomyces cerevisiae.
AB  - Biochemical evidence suggesting that the predominant form of Mediator in the
      yeast Saccharomyces cerevisiae might be one in which the complex is associated
      with RNA polymerase II to form a holoenzyme has led to the proposition of a
      holoenzyme-based model for transcription initiation. We report that polymerase
      free Mediator, isolated early on during a whole-cell extract fractionation
      protocol, is in fact the most abundant form of the Mediator complex. The
      existence of free Mediator would make possible independent recruitment of
      Mediator and RNA polymerase II to the pre-initiation complex. This is in
      agreement with reports from in vivo studies of time and spatial independence of
      Mediator and RNA polymerase II promoter interaction, with current models of pre
      initiation complex structure in which promoter DNA upstream of the transcription
      start site is positioned between Mediator and polymerase, and with the proposed
      role of Mediator as the major component of the Scaffold complex involved in
      transcription reinitiation.

PMID- 16002406
TI  - Cyclin-dependent kinase inhibitors uncouple cell cycle progression from
      mitochondrial apoptotic functions in DNA-damaged cancer cells.
AB  - DNA damage results in transcriptional induction of p53 target genes, including
      the cyclin-dependent kinase (CDK) inhibitor p21(Cip1) (CDKN1A) and the
      proapoptotic Bcl-2 family member p53 up-regulated modulator of apoptosis (PUMA).
      Depending on the cellular context, p21(Cip1) and PUMA mediate cell cycle arrest
      and apoptosis, respectively. By imposing cell cycle arrest at the expense of
      apoptosis, p21(Cip1) can sharply reduce the effectiveness of DNA-damaging
      anticancer agents in colorectal cancer cells. We investigated the link between
      cell cycle progression and the onset of apoptosis in DNA-damaged cells by
      analyzing the activation of the apoptotic cascade in p21(Cip1)-deficient HCT116
      colorectal cancer cells. DNA damage induced a similar level of p53 activation and
      PUMA induction in p21(Cip1)-deficient cells compared with wild-type isogenic
      counterparts. p21(Cip1) did not act as a direct blocker of PUMA. However, only
      p21(Cip1)-deficient cells showed extensive cytochrome c release, mitochondrial
      membrane depolarization, and caspase activation. An increase in caspase
      activation occurred as these cells reached M-phase and incurred polyploidy. When
      ectopically expressed in p21(Cip1)-deficient HCT116 cells, p21(Cip1), its family
      member p27(Kip1), and the structurally unrelated CDK inhibitor p16(Ink4a) were
      similarly effective at causing cell cycle arrest and inhibiting DNA damage
      induced apoptotic events such as cytochrome c release, mitochondrial membrane
      depolarization, and activation of the caspase cascade. These observations suggest
      that by blocking dysregulated cell cycle progression, CDK inhibitors can
      influence the sensitivity of the mitochondria to proapoptotic signals in DNA
      damage-induced cancer cells.

PMID- 16002405
TI  - DNA polymerase lambda protects mouse fibroblasts against oxidative DNA damage and
      is recruited to sites of DNA damage/repair.
AB  - DNA polymerase lambda (pol lambda) is a member of the X family of DNA polymerases
      that has been implicated in both base excision repair and non-homologous end
      joining through in vitro studies. However, to date, no phenotype has been
      associated with cells deficient in this DNA polymerase. Here we show that pol
      lambda null mouse fibroblasts are hypersensitive to oxidative DNA damaging
      agents, suggesting a role of pol lambda in protection of cells against the
      cytotoxic effects of oxidized DNA. Additionally, pol lambda co-immunoprecipitates
      with an oxidized base DNA glycosylase, single-strand-selective monofunctional
      uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ.
      From these data, we conclude that pol lambda protects cells against oxidative
      stress and suggest that it participates in oxidative DNA damage base excision
      repair.

PMID- 16002407
TI  - Fibromodulin gene transcription is induced by ultraviolet irradiation, and its
      regulation is impaired in senescent human fibroblasts.
AB  - Cells undergoing replicative senescence display an altered pattern of gene
      expression. Senescent fibroblasts show significant changes in the expression of
      mRNAs encoding extracellular matrix-remodeling proteins; among these mRNAs, the
      mRNA encoding fibromodulin is highly decreased in these cells. To understand the
      molecular basis of this phenomenon, we explored the regulatory mechanisms of the
      human fibromodulin gene. We found that fibromodulin gene promoter contains a cis
      element, crucial for its basal expression, that forms a DNA-protein complex when
      exposed to nuclear extracts from exponentially growing human fibroblasts and not
      to extracts from cells undergoing senescence by repeated in vitro passages or by
      mild oxidative stress. The purification of this complex showed that it contains
      the damage-specific DNA-binding protein DDB-1. The latter is known to be induced
      by UV irradiation; therefore we checked whether fibromodulin gene promoter is
      regulated upon the exposure of the cells to UV rays. The results showed that, in
      exponentially growing fibroblasts, the promoter efficiency is increased by UV
      irradiation and the DDB-1-containing complex is robustly enriched in cells
      exposed to UV light. Accordingly, in these experimental conditions the endogenous
      fibromodulin mRNA accumulates to very high levels. On the contrary, senescent
      cells did not show any activation of the fibromodulin gene promoter, any
      induction of the DDB-1-containing complex, or any accumulation of fibromodulin
      mRNA. These phenomena are accompanied in senescent cells by a decrease of the UV
      damaged DNA binding activity.

PMID- 16002408
TI  - Mutations of the PC2 substrate binding pocket alter enzyme specificity.
AB  - By taking advantage of the recently published furin structure, whose catalytic
      domain shares high homology with other proprotein convertases, we designed
      mutations in the catalytic domain of PC2, altering residues Ser206, Thr271,
      Asp278, ArgGlu282, AlaSer323, Leu341, Asn365, and Ser380, which are both
      conserved and specific to this convertase, and substituting residues specific to
      PC1 and/or furin. In order to investigate the determinants of PC2 specificity, we
      have tested the mutated enzymes against a set of proenkephalin-derived
      substrates, as well as substrates representing Arg, Ala, Leu, Phe, and Glu
      positional scanning variants of a peptide B-derived substrate. We found that the
      exchange of the Ser206 residue with Arg or Lys led to a total loss of activity.
      Increased positive charge of the substrate generally resulted in an increased
      specificity constant. Most intriguingly, the RE281GR mutation, corresponding to a
      residue placed distantly in the S6 pocket, evoked the largest changes in the
      specificity pattern. The D278E and N356S mutations resulted in distinct
      alterations in PC2 substrate preferences. However, when other residues that
      distinguish PC2 from other convertases were substituted with PC1-like or furin
      like equivalents, there was no significant alteration of the PC2 specificity
      pattern, suggesting that the overall structure of the substrate binding cleft
      rather than individual residues specifies substrate binding.

PMID- 16002409
TI  - Phosphorylation of the A-kinase-anchoring protein Yotiao contributes to protein
      kinase A regulation of a heart potassium channel.
AB  - Regulation of the heart by the sympathetic nervous system, fundamental to the
      physiological response to stress and exercise, requires coordinated
      phosphorylation of multiple downstream molecular targets, including the I(Ks)
      (slowly activating potassium current) channel. Sympathetic nervous system
      stimulation increases intracellular cAMP for which targeted regulation is
      directed in large part by distinct scaffold or anchoring proteins. Yotiao is an A
      kinase-anchoring protein (AKAP) that recruits the cyclic AMP-dependent protein
      kinase (protein kinase A (PKA)) and protein phosphatase 1 to the carboxyl
      terminus of the I(Ks) channel to form a molecular complex and control its
      phosphorylation state, crucial to the cardiac cellular response to sympathetic
      nervous system stimulation. Here we report that Yotiao itself is a substrate for
      PKA phosphorylation, and we identify a Yotiao amino-terminal (N-T) residue (Ser
      43) that is PKA-phosphorylated in response to beta-adrenergic receptor
      stimulation. The replacement of Ser-43 by Ala ablates the PKA phosphorylation of
      N-T Yotiao and markedly diminishes the functional response of the wild type and
      pseudo-phosphorylated I(Ks) channel to cAMP but neither prevents the PKA
      phosphorylation of KCNQ1 nor its binding to Yotiao. These results suggest, for
      the first time, a critical role for the PKA phosphorylation of an AKAP in the
      functional regulation of an ion channel protein and postphosphorylation
      allosteric modulation of the I(Ks) channel by Yotiao.

PMID- 16002410
TI  - Suppression of urokinase expression and invasion by a soybean Kunitz trypsin
      inhibitor are mediated through inhibition of Src-dependent signaling pathways.
AB  - A soybean Kunitz trypsin inhibitor (KTI) interacts with cells as a negative
      modulator of the invasive cells. Using complementary pharmacological and genetic
      approaches, we provide novel findings regarding mechanisms by which KTI inhibits
      signaling pathways in ovarian cancer cells leading to invasion. Transforming
      growth factor-beta1 (TGF-beta1) directly activates Src kinase, which in turn
      activates ERK-phosphatidylinositol 3-kinase/Akt, the downstream targets of Src,
      for urokinase-type plasminogen activator (uPA) up-regulation in human ovarian
      cancer HRA cells. Preincubation of the HRA cells with KTI reduced the ability of
      TGF-beta1 to trigger the uPA expression at the gene level and at the protein
      level. To further elucidate the mechanism of the KTI-dependent suppressive effect
      of TGF-beta1-induced uPA expression and invasion, we investigated which signaling
      pathway transduced by KTI is responsible for this inhibitory effect. Here, we
      show that 1) KTI suppressed TGF-beta1-induced phosphorylation of Src, ERK1/2, and
      Akt by 40-60%; 2) KTI was insensitive to suppress the phosphorylation of ERK1/2
      and Akt in the constitutively active (CA)-c-Src (Y529F) cells; 3) uPA expression
      was up-regulated in TGF-beta1-stimulated HRA cells and in unstimulated Y529F
      cells; 4) the addition of KTI reduced the TGF-beta1-induced increase of uPA gene
      and protein expression in the wild-type c-Src-transfected cells (in contrast, KTI
      could not inhibit uPA expression in the Y529F cells); and 5) CA-c-Src
      transfection resulted in a 2-fold increase in invasiveness, whereas KTI did not
      reduce invasion of the Y529F cells. Using additional complementary genetic
      approaches (CA-MEK1, CA-Akt, or kinase-dead-Akt), we conclude that KTI may
      suppress uPA expression and promotion of invasion possibly through one or more
      upstream targets of Src.

PMID- 16002411
TI  - Dietary calcium, obesity and hypertension--the end of the road?

PMID- 16002412
TI  - Defective osteoblast function may be responsible for bone loss from the proximal
      femur despite pamidronate therapy.

PMID- 16002413
TI  - Letter re: Long-term persistence of the urine calcium-lowering effect of
      potassium bicarbonate in postmenopausal women.

PMID- 16002414
TI  - Letter re: Limited accuracy of surrogates of insulin resistance during puberty in
      obese and lean children at risk for altered glucoregulation.

PMID- 16002415
TI  - Letter re: The biological variation of testosterone and sex hormone-binding
      globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a
      surrogate marker of insulin resistance.

PMID- 16002416
TI  - Angiotensin-converting enzyme (ACE) haplotypes and cyclosporine A (CsA) response:
      a model of the complex relationship between ACE quantitative trait locus and
      pathological phenotypes.
AB  - It is highly controversial to define the role of angiotensin-converting enzyme
      (ACE) polymorphisms in essential hypertension. We studied a group of patients in
      whom hypertension was the major side effect of treatment by cyclosporine A (CsA).
      This study group comprised 227 Italian patients with nephrotic syndrome, 103 of
      which were treated with CsA and had different outcome. Forty-nine patients
      developed serious hypertension that was reversed after withdrawal of drug. ACE
      haplotypes were determined by a combination of molecular and statistical methods
      after verifying genotypes of six intragenic single nucleotide polymorphisms in
      304 Italian blood donors and assembling them in clades (A, B, C) that include 95%
      of observed haplotypes. The association between ACE clade combinations and serum
      enzymatic levels confirmed the previous results about a role of an unidentified
      genetic variant at the 5' of the intragenic recombination site located near
      intron 7. ACE clades were then determined in patients, and regression methods
      were used to analyze variables associated with CsA responsivity and progression
      to renal failure. ACE genotype and responsiveness to CsA were strictly
      associated, because homozygosis for ACE B clade was able to influence CsA
      sensitivity. This highlights the role of 5' variants, which differentiate clades
      B and C. Other genetic markers were tested to search for possible additive
      effects. We found that PAI-1 4G allele was associated with progression to renal
      failure in the group of CsA-treated patients. Our results are in agreement with
      the hypothesis, raised after experimental results obtained in mouse models, that
      the effect of ACE polymorphisms on blood pressure is detectable once
      environmental factors, like CsA treatment in our case, overcome physiological
      homeostatic mechanisms.

PMID- 16002417
TI  - Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett
      syndrome.
AB  - Rett syndrome (RTT) is a severe form of mental retardation, which is caused by
      spontaneous mutations in the X-linked gene MECP2. How the loss of MeCP2 function
      leads to RTT is currently unknown. Mice lacking the Mecp2 gene initially show
      normal postnatal development but later acquire neurological phenotypes, including
      heightened anxiety, that resemble RTT. The MECP2 gene encodes a methyl-CpG
      binding protein that can act as a transcriptional repressor. Using cDNA
      microarrays, we found that Mecp2-null animals differentially express several
      genes that are induced during the stress response by glucocorticoids. Increased
      levels of mRNAs for serum glucocorticoid-inducible kinase 1 (Sgk) and FK506
      binding protein 51 (Fkbp5) were observed before and after onset of neurological
      symptoms, but plasma glucocorticoid was not significantly elevated in Mecp2-null
      mice. MeCP2 is bound to the Fkbp5 and Sgk genes in brain and may function as a
      modulator of glucocorticoid-inducible gene expression. Given the known
      deleterious effect of glucocorticoid exposure on brain development, our data
      raise the possibility that disruption of MeCP2-dependent regulation of stress
      responsive genes contributes to the symptoms of RTT.

PMID- 16002418
TI  - Strategies for adaptation of Suaeda physophora, Haloxylon ammodendron and
      Haloxylon persicum to a saline environment during seed-germination stage.
AB  - BACKGROUND AND AIMS: Germination is very important for plant establishment in
      arid regions. The strategies taken by halophytes during the seed germination
      stage to adapt to saline environments in an arid zone were investigated in Suaeda
      physophora (euhalophyte), Haloxylon ammodendron (xero-halophyte) and Haloxylon
      persicum (xerophyte). METHODS: Seeds of S. physophora, H. ammodendron and H.
      persicum were exposed to a range of iso-osmotic NaCl and PEG solutions. Seed
      germination in, and recovery germination from, high NaCl were recorded. The
      effects of iso-osmotic NaCl and PEG on seed water uptake and changes in ion
      content were measured. In addition, the structure of seeds and Na+ distribution
      in the seed coat and embryos of dry seeds were investigated. KEY RESULTS: The
      relative increase in fresh weight of germinating seeds was markedly reduced in 
      2.24 MPa PEG compared with that in -2.24 MPa NaCl, while the opposite trend was
      found in concentration of K+ during the initial 9 h for all species. Haloxylon
      ammodendron and S. physophora had a higher recovery germination from -3.13 MPa
      NaCl compared with H. persicum. Seeds of all species had no endosperm. More Na+
      was compartmentalized in the seed coats of the two halophytic species compared
      with that in the xerophyte H. persicum. CONCLUSIONS: The effect of NaCl on seed
      germination was due to both osmotic stress and ion toxicity for the three
      species. High soil salinity and a high content of Na+ in seeds may induce more
      seeds to remain ungerminated in S. physophora and H. ammodendron. Morphological
      structure and adaptation to salinity during seed germination may determine the
      geographical distribution of H. ammodendron and S. physophora in certain saline
      regions.

PMID- 16002419
TI  - Effects of CAPE-like compounds on HIV replication in vitro and modulation of
      cytokines in vivo.
AB  - OBJECTIVES: Five CAPE-like compounds, namely caffeic acid phenethyl ester (CAPE),
      methyl caffeate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl
      dimethyl caffeate (PEDMC) and phenethyl 3-(4-bromophenyl)acrylic (BrCAPE) were
      tested for their anti-HIV replication in vitro and immune modulation effects in
      vivo. METHODS: Short-term cytotoxicity was assessed by Trypan Blue stain and MTT
      assay. For antiviral assays, M-tropic (strain JRCSF), T-tropic (strain NL-4-3)
      and dual tropic (strain 89.6) HIV isolates were used in peripheral blood
      mononuclear cell (PBMC) culture. RESULTS: None of these CAPE-like compounds
      showed significant cytotoxicity in the treatment of PBMCs. By P24 EIA tests,
      CAPE, MC and EC significantly inhibited HIV replication in PBMC cells, but PEDMC
      and BrCAPE showed only slightly inhibitory effects. The in vivo modulatory
      effects on six cytokines [interleukin (IL)-2, IL-4, IL-6, interferon (IFN)-gamma,
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and soluble Fas] were
      analysed. BALB/c mice treated with different doses or not treated with these CAPE
      like chemicals showed that cytokines were increased to different extents by the
      different treatments. However, the concentrations of IL-6 and GM-CSF were not
      significantly affected by administration of any of these compounds (P > 0.05).
      CONCLUSIONS: The different effects of treatments on anti-HIV replication and
      cytokine modulation suggested that these compounds affect virological and
      immunological response via different mechanisms. The virological and
      immunological mechanisms and response to these treatments need to be elaborated
      in further studies in order to derive the structural features of more effective
      compounds. Since neither death nor pathological change in the mice were observed
      in this study, these CAPE-like compounds are worth studying further as potential
      chemotherapy agents for anti-HIV infection and cytokine modulation.

PMID- 16002420
TI  - Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in
      patients with complicated intra-abdominal infection.
AB  - OBJECTIVES: We investigated the population pharmacokinetics and pharmacodynamics
      of piperacillin and tazobactam in hospitalized patients. PATIENTS AND METHODS: A
      multicentre, randomized clinical trial was conducted in hospitalized patients
      with complicated intra-abdominal infection. Patients received
      piperacillin/tazobactam administered by either continuous infusion (13.5 g over
      24 h, n = 130) or intermittent infusion (3.375 g every 6 h, n = 132). NONMEM was
      used to perform population pharmacokinetic analysis in a subset of patients (n =
      56) who had serum samples obtained at steady-state for drug concentration
      analyses. Classification and regression tree analysis was used to identify the
      breakpoints of piperacillin PK-PD indexes in 94 patients with causative
      pathogen's MIC. RESULTS: A one-compartment model was applied to fit the data.
      Creatinine clearance and body weight were the most significant variables to
      explain patient variability in piperacillin and tazobactam clearance and volume
      of distribution. The infusion method had no influence on PK parameters. For
      patients (n = 30) receiving intermittent infusion in the pharmacokinetic study,
      mean Cmax and half-life were 122.22 mg/L and 1.17 h for piperacillin, and 15.74
      mg/L and 1.81 h for tazobactam. For patients (n = 26) receiving continuous
      infusion in the pharmacokinetic study, mean steady-state concentration was 35.31
      +/- 12.15 mg/L for piperacillin and 7.29 +/- 3.28 mg/L for tazobactam. As a
      result of a low rate of failures (<11%) observed in the trial and the low MICs
      for infecting pathogens, no association could be established between
      clinical/microbiological outcome and drug exposure. CONCLUSIONS: Intermittent
      infusion and continuous infusion of piperacillin and tazobactam provided
      sufficient drug exposure to treat those pathogens commonly implicated in intra
      abdominal infections.

PMID- 16002421
TI  - Enhanced efficacy of single-dose versus multi-dose azithromycin regimens in
      preclinical infection models.
AB  - OBJECTIVES: As a result of the prolonged half-life and unique pharmacokinetic and
      pharmacodynamic (PK-PD) characteristics of azithromycin, shorter dosing regimens
      are being evaluated for the treatment of community-acquired infections. To
      provide further support for a shorter dosing regimen, the efficacy of
      azithromycin was determined in preclinical infection models comparing single-
      versus multi-dose regimens. METHODS: The efficacy of single versus multi-dose
      regimens of azithromycin was compared in mouse pneumonia, acute peritonitis, and
      neutropenic thigh infection models and in a gerbil model of Haemophilus
      influenzae acute otitis media. Azithromycin was administered as a single oral
      dose on the first treatment day, or as two divided doses over 2 treatment days,
      or as three divided doses over 3 treatment days. The pharmacokinetics of
      azithromycin was profiled following single and multi-dose regimens with the
      single dose data fit to an Emax model to characterize the PK-PD of azithromycin.
      RESULTS: In the mouse efficacy models, administration of single-dose azithromycin
      produced superior rates of survival and bacterial clearance compared with the
      same total dose divided over 2 or 3 days. In the gerbil model, a single dose
      sterilized the middle ear and more rapidly cleared H. influenzae. The
      pharmacokinetic evaluation confirmed similar total exposure (AUC) in serum and
      pulmonary tissue for the three regimens. Correlation of PK-PD parameters and
      antimicrobial efficacy confirmed a concentration-dependent and dosing-independent
      relationship for azithromycin. CONCLUSIONS: These data are consistent with data
      reported from clinical studies and indicate that a single-dose regimen would be
      at least as effective as the same dose administered over several days.

PMID- 16002423
TI  - Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1
      cytokines in the pathogenesis of hemophagocytic syndrome.
AB  - The primary infection of Epstein-Barr virus (EBV) may result in fatal infectious
      mononucleosis or hemophagocytic syndrome (HPS) in 2 diseases; that is, X-linked
      lymphoproliferative disorder (XLP) and hemophagocytic lymphohistiocytosis (HLH).
      XLP is linked to mutations of the SAP/SH2D1A gene with dysregulated T-cell
      activation in response to EBV infection. Patients with sporadic HLH, however,
      usually have no mutation of the SAP/SH2D1A gene, and EBV latent membrane protein
      1 (LMP1) can up-regulate Th1 cytokines in EBV-infected T cells. Since both
      diseases share common manifestations of HPS, it is important to clarify whether a
      cross-talk exists between signaling lymphocyte activation molecule (SLAM)
      associated protein (SAP) and LMP1-mediated pathways to explain the common
      pathogenesis of HPS. In this study, no mutation of the SAP/SH2D1A gene at exon
      2/3 was detected in 7 HLH cases. Interestingly, EBV LMP1 could transcriptionally
      inhibit the expression of SAP/SH2D1A and activate downstream molecules ERK and
      interferon-gamma (IFN-gamma). LMP1-mediated SAP/ERK/IFN-gamma signals appear to
      act via the TNF receptor-associated factor (TRAF)2,5/nuclear factor kappaB (NF
      kappaB) pathway, since dominant-negative TRAF2/5 and NF-kappaB inhibitor could
      rescue SAP expression and downregulate IFN-gamma. Although HLH is genetically
      distinct from XLP, our data suggest that both diseases share a common signal
      pathway, through either the mutation or LMP1-mediated suppression of the SAP
      gene, leading to overt T-cell activation and enhanced Th1 cytokine secretion in
      response to EBV infection.

PMID- 16002422
TI  - Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells
      during acute graft-versus-host disease.
AB  - CD4+CD25+ regulatory T cells (T(regs)) have been shown to inhibit graft-versus
      host disease (GVHD) in murine models, and this suppression was mediated by
      T(regs) expressing the lymphoid homing molecule l-selectin. Here, we demonstrate
      that T(regs) lacking expression of the chemokine receptor CCR5 were far less
      effective in preventing lethality from GVHD. Survival of irradiated recipient
      animals given transplants supplemented with CCR5-/- T(regs) was significantly
      decreased, and GVHD scores were enhanced compared with animals receiving wild
      type (WT) T(regs). CCR5-/- T(regs) were functional in suppressing T-cell
      proliferation in vitro and ex vivo. However, although the accumulation of T(regs)
      within lymphoid tissues during the first week after transplantation was not
      dependent on CCR5, the lack of function of CCR5-/- T(regs) correlated with
      impaired accumulation of these cells in the liver, lung, spleen, and mesenteric
      lymph node, more than one week after transplantation. These data are the first to
      definitively demonstrate a requirement for CCR5 in T(reg) function, and indicate
      that in addition to their previously defined role in inhibiting effector T-cell
      expansion in lymphoid tissues during GVHD, later recruitment of T(regs) to both
      lymphoid tissues and GVHD target organs is important in their ability to prolong
      survival after allogeneic bone marrow transplantation.

PMID- 16002424
TI  - Discovery of novel immunostimulants by dendritic-cell-based functional screening.
AB  - Immunostimulants represent an emerging class of drugs for the treatment of
      infectious disorders and cancer. CpG oligonucleotides and imiquimod, prototypic
      drugs in this category, are now known to activate dendritic cells (DCs). Here we
      report the development of a highly sensitive, unbiased functional screen to
      detect DC-stimulatory signals. Because interleukin-1beta (IL-1beta) mRNA
      expression is closely associated with DC activation, we engineered DCs to stably
      express a fluorescent marker gene under the control of IL-1beta promoter. By
      screening about 3000 compounds with the resulting DC biosensor clone, we
      identified DC-stimulatory potentials of topoisomerase I inhibitors (camptothecin
      derivatives) and microtubule depolymerizing drugs (colchicine and
      podophyllotoxin). In response to treatment with each agent, bone marrow-derived
      DC preparations exhibited characteristic phenotypic and/or functional changes
      associated with DC activation. All of these agents also triggered nuclear factor
      kappaB (NFkappaB) activation in DCs, suggesting a common pharmacologic mechanism
      of action. Furthermore, locally administered colchicine induced in situ
      maturation and migration of DCs and augmented both humoral and cellular immune
      responses. These results support the practical utility of the DC-based biosensor
      system to discover novel DC-targeted immunostimulants and unveil previously
      unrecognized (and totally unexpected) pharmacologic activities of several drugs
      that are commonly used for the treatment of various disorders.

PMID- 16002425
TI  - Genomic stability and functional activity may be lost in telomerase-transduced
      human CD8+ T lymphocytes.
AB  - To obtain the large amount of T cells required for adoptive immunotherapy in a
      clinical setting, T-cell lifespan extension by human telomerase reverse
      transcriptase (hTERT) transduction is of particular interest. However,
      constitutive expression of hTERT is associated with malignant transformation and
      thus warrants a detailed evaluation of the safety of hTERT-transduced T cells
      before clinical application. In view of this, we performed an extensive
      cytogenetic analysis of hTERT-transduced MART-1 (melanoma antigen recognized by T
      cell 1)-and human papillomavirus type 16 (HPV16) E7-specific human CD8+ cytotoxic
      T lymphocytes (CTLs), reactive against melanoma and cervical carcinoma,
      respectively. Our results, obtained by (spectral) karyotyping and array
      comparative genomic hybridization, showed the development of minor chromosomal
      aberrations in an hTERT-transduced MART-1-specific CTL clone, whereas severe
      clonal aberrations were detected in an hTERT-transduced HPV16 E7-specific CTL
      clone. Furthermore, hTERT transduction did not protect CTLs from
      immunosenescence, because the HPV16 E7-specific, hTERT-transduced CTL clone
      showed a decreased functional activity on prolonged culture. Although the general
      frequency of major chromosomal aberrations in hTERT-transduced CTLs and the in
      vivo significance of our observations remain still unclear at this point, the
      currently available data suggest that clinical application of hTERT-transduced
      CTLs should proceed with caution.

PMID- 16002426
TI  - A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination
      with high-dose etoposide and cyclophosphamide followed by autologous stem cell
      transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma.
AB  - We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in
      combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and
      cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell
      transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL).
      Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab
      tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab
      tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone
      marrow biopsy was done on day -7 to estimate radiation dose and stem cells were
      reinfused when the radiation dose was estimated to be less than 5 cGy. The median
      90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi;
      range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse
      large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo
      therapy treatments was 2. The treatment was well tolerated. The median times to
      reach an absolute neutrophil count greater than 500/microL and platelet count
      more than 20,000/microL were 10 days and 12 days, respectively. There were 2
      deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated
      overall survival and relapse-free survival rates are 92% and 78%, respectively.
      We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with
      high-dose etoposide and cyclophosphamide without an increase in transplant
      related toxicity or delayed engraftment.

PMID- 16002427
TI  - A specific role of integrin Mac-1 in accelerated macrophage efflux to the
      lymphatics.
AB  - In response to injury, monocytes migrate to the site of inflammation, where they
      differentiate into macrophages and participate in various biologic processes.
      However, their fate during the resolution of acute inflammation is not fully
      understood. Here, we show that inflammatory macrophages do not die locally by
      apoptosis; rather, they migrate across the peritoneal mesothelium to the
      lymphatics, through which they further migrate to the lymph nodes and to the
      blood circulation. Macrophage efflux is enhanced considerably on cell activation,
      and such accelerated macrophage migration is dependent specifically on integrin
      Mac-1, and can be blocked by addition of its antagonist. Thus, genetic
      inactivation of Mac-1 in mice inhibits the accelerated macrophage efflux from the
      inflammatory site to the lymphatics, but it does not compromise the accumulation
      of blood monocytes into the inflammatory site. Together, our study demonstrates
      that Mac-1 is involved specifically in the efflux of activated macrophages to the
      lymphatics, suggesting that Mac-1 may play an important role in the removal of
      local inflammatory macrophages and in their subsequent migration to the lymph
      nodes, a process that is critical to the development of the adaptive immunity.

PMID- 16002428
TI  - The kinetics of clonal dominance in myeloproliferative disorders.
AB  - To study clonal evolution in myeloproliferative disorders, we used stochastic
      models of hematopoiesis for mouse and cat, species for which the in vivo kinetics
      of hematopoietic stem cells (HSCs) have been experimentally defined. We
      determined the consequence if 1 HSC became able to survive without the support of
      a microenvironmental niche while the rest of its behavior did not change.
      Neoplastic cells persisted and dominated hematopoiesis in 14% of mice and 17% of
      cats, requiring mean times of 2.5 +/- 0.5 and 7.0 +/- 1.2 years, respectively
      (n=1000 simulations/species). In both species, when the number of neoplastic HSCs
      exceeded 0.5% of all HSCs, clonal dominance was inevitable. Our results can
      explain the absence of clonal myeloproliferative disorders in mice (lifetime, 2
      years), are consistent with clinical observations in cats, and provide insight
      into the progression of chronic myelogenous leukemia (CML) in humans. They also
      demonstrate that competition for microenvironmental support can lead to the
      suppression of normal hematopoiesis as neoplasia evolves. Toxic or immunologic
      suppression of normal HSCs is not required.

PMID- 16002429
TI  - Sequential deregulation of NK cell subset distribution and function starting in
      acute HIV-1 infection.
AB  - Natural killer (NK) cells are critical in the first-line defense against viral
      infections. Chronic HIV-1 infection leads to a perturbation in the NK cell
      compartment, yet the kinetics of this deregulation and the functional
      consequences are unclear. Here, we characterized changes in the NK cell
      compartment longitudinally by multiparameter flow cytometry, starting in acute
      HIV-1 infection. Acute HIV-1 infection was associated with elevated NK cell
      numbers, with an expansion of CD3(neg)CD56(dim)CD16(pos) NK cells and an early
      depletion of CD3(neg)CD56(bright)CD16(neg) NK cells. Ongoing viral replication
      resulted in a depletion of CD3(neg)CD56(dim)CD16(pos) NK cells with a paralleled
      increase in functionally anergic CD3(neg)CD56(neg)CD16(pos) NK cells, accompanied
      by reduced functional activity, as measured by CD107a expression and cytokine
      secretion. Taken together, these studies demonstrate a sequential impairment of
      NK cell function with persistent viral replication resulting from a progressive
      deregulation of NK cell subsets with distinct functional properties.

PMID- 16002430
TI  - Studies on the basis for the properties of fibrin produced from fibrinogen
      containing gamma' chains.
AB  - Human fibrinogen 1 is homodimeric with respect to its gamma chains (gammaA
      gammaA'), whereas fibrinogen 2 molecules each contain one gammaA (gammaA1-411V)
      and one gamma' chain, which differ by containing a unique C-terminal sequence
      from gamma'408 to 427L that binds thrombin and factor XIII. We investigated the
      structural and functional features of these fibrins and made several
      observations. First, thrombin-treated fibrinogen 2 produced finer, more branched
      clot networks than did fibrin 1. These known differences in network structure
      were attributable to delayed release of fibrinopeptide (FP) A from fibrinogen 2
      by thrombin, which in turn was likely caused by allosteric changes at the
      thrombin catalytic site induced by thrombin exosite 2 binding to the gamma'
      chains. Second, cross-linking of fibrin gamma chains was virtually the same for
      both types of fibrin. Third, the acceleratory effect of fibrin on thrombin
      mediated XIII activation was more prominent with fibrin 1 than with fibrin 2, and
      this was also attributable to allosteric changes at the catalytic site induced by
      thrombin binding to gamma' chains. Fourth, fibrinolysis of fibrin 2 was delayed
      compared with fibrin 1. Altogether, differences between the structure and
      function of fibrins 1 and 2 are attributable to the effects of thrombin binding
      to gamma' chains.

PMID- 16002431
TI  - Rapid simulation and analysis of isotopomer distributions using constraints based
      on enzyme mechanisms: an example from HT29 cancer cells.
AB  - MOTIVATION: Addition of labeled substrates and the measurement of the subsequent
      distribution of the labels in isotopomers in reaction networks provide a unique
      method for assessing metabolic fluxes in whole cells. However, owing to
      insufficiency of information, attempts to quantify the fluxes often yield
      multiple possible sets of solutions that are consistent with a given experimental
      pattern of isotopomers. In the study of the pentose phosphate pathways, the need
      to consider isotope exchange reactions of transketolase (TK) and transaldolase
      (TA) (which in past analyses have often been ignored) magnifies this problem; but
      accounting for the interrelation between the fluxes known from biochemical
      studies and kinetic modeling solves it. The mathematical relationships between
      kinetic and equilibrium constants restrict the domain of estimated fluxes to the
      ones compatible not only with a given set of experimental data, but also with
      other biochemical information. METHOD: We present software that integrates
      kinetic modeling with isotopomer distribution analysis. It solves the ordinary
      differential equations for total concentrations (accounting for the kinetic
      mechanisms) as well as for all isotopomers in glycolysis and the pentose
      phosphate pathway (PPP). In the PPP the fluxes created in the TK and TA reactions
      are expressed through unitary rate constants. The algorithms that account for all
      the kinetic and equilbrium constant constraints are integrated with the
      previously developed algorithms, which have been further optimized. The most time
      consuming calculations were programmed directly in assembly language; this gave
      an order of magnitude decrease in the computation time, thus allowing analysis of
      more complex systems. The software was developed as C-code linked to a program
      written in Mathematica (Wolfram Research, Champaign, IL), and also as a C++
      program independent from Mathematica. RESULTS: Implementing constraints imposed
      by kinetic and equilibrium constants in the isotopomer distribution analysis in
      the data from the cancer cells eliminated estimates of fluxes that were
      inconsistent with the kinetic mechanisms of TK and TA. Fluxes measured
      experimentally in cells can be used to estimate better the kinetics of TK and TA
      as they operate in situ. Thus, our approach of integrating various methods for in
      situ flux analysis opens up the possibility of designing new types of experiments
      to probe metabolic interrelationships, including the incorporation of additional
      biochemical information. AVAILABILITY: Software is available freely at:
      http://www.bq.ub.es/bioqint/selivanov.htm CONTACT: martacascante@ub.edu

PMID- 16002432
TI  - A parsimonious tree-grow method for haplotype inference.
AB  - MOTIVATION: Haplotype information has become increasingly important in analyzing
      fine-scale molecular genetics data, such as disease genes mapping and drug
      design. Parsimony haplotyping is one of haplotyping problems belonging to NP-hard
      class. RESULTS: In this paper, we aim to develop a novel algorithm for the
      haplotype inference problem with the parsimony criterion, based on a parsimonious
      tree-grow method (PTG). PTG is a heuristic algorithm that can find the minimum
      number of distinct haplotypes based on the criterion of keeping all genotypes
      resolved during tree-grow process. In addition, a block-partitioning method is
      also proposed to improve the computational efficiency. We show that the proposed
      approach is not only effective with a high accuracy, but also very efficient with
      the computational complexity in the order of O(m2n) time for n single nucleotide
      polymorphism sites in m individual genotypes. AVAILABILITY: The software is
      available upon request from the authors, or from
      http://zhangroup.aporc.org/bioinfo/ptg/ CONTACT: chen@elec.osaka-sandai.ac.jp
      SUPPLEMENTARY INFORMATION: Supporting materials is available from
      http://zhangroup.aporc.org/bioinfo/ptg/bti572supplementary.pdf

PMID- 16002433
TI  - Changes in attitude, changes in latitude: nuclear receptors remodeling chromatin
      to regulate transcription.
AB  - Nuclear receptors (NRs) are a large family of ligand-dependent transcription
      factors that regulate important physiological processes. To activate or repress
      genes assembled naturally as chromatin, NRs recruit two distinct enzymatic
      activities, namely histone-modifying enzymes and ATP-dependent chromatin
      remodeling complexes, to alter local chromatin structure at target gene
      promoters. In this review, we examine the functional relationship between ATP
      dependent chromatin remodeling complexes and NRs in the context of
      transcriptional regulation. Using the steroid-responsive mouse mammary tumor
      virus promoter as a model system, we discuss in detail the molecular mechanisms
      underlying the recruitment of these complexes and subsequent chromatin structure
      changes catalyzed by this group of enzymes. In addition, we extend the discussion
      to other NR-regulated promoters including the pS2 promoter. Finally, we summarize
      specific principles governing this critical relationship, identify unanswered
      questions and discuss the potential application of these principles in rational
      drug design.

PMID- 16002434
TI  - Large-scale in silico and microarray-based identification of direct 1,25
      dihydroxyvitamin D3 target genes.
AB  - 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] regulates calcium homeostasis and
      controls cellular differentiation and proliferation. The vitamin D receptor (VDR)
      is a ligand-regulated transcription factor that recognizes cognate vitamin D
      response elements (VDREs) formed by direct or everted repeats of PuG(G/T)TCA
      motifs separated by 3 or 6 bp (DR3 or ER6). Here, we have identified direct
      1,25(OH)2D3 target genes by combining 35,000+ gene microarrays and genome-wide
      screens for consensus DR3 and ER6 elements, and DR3 elements containing single
      nucleotide substitutions. We find that the effect of a nucleotide substitution on
      VDR binding in vitro does not predict VDRE function in vivo, because
      substitutions that disrupted binding in vitro were found in several functional
      elements. Hu133A microarray analyses, performed with RNA from human SCC25 cells
      treated with 1,25(OH)2D3 and protein synthesis inhibitor cycloheximide,
      identified more than 900 regulated genes. VDREs lying within -10 to +5 kb of 5'
      ends were assigned to 65% of these genes, and VDR binding was confirmed to
      several elements in vivo. A screen of the mouse genome identified more than 3000
      conserved VDREs, and 158 human genes containing conserved elements were
      1,25(OH2)D3-regulated on Hu133A microarrays. These experiments also revealed 16
      VDREs in 11 of 12 genes induced more than 10-fold in our previous microarray
      study, five elements in the human gene encoding the epithelial calcium channel
      TRPV6, as well as novel 1,25(OH2)D3 target genes implicated in regulation of cell
      cycle progression. The combined approaches used here thus provide numerous
      insights into the direct target genes underlying the broad physiological actions
      of 1,25(OH)2D3.

PMID- 16002435
TI  - Intermedin functions as a pituitary paracrine factor regulating prolactin
      release.
AB  - Calcitonin, alpha- and beta-calcitonin gene-related peptides, amylin, and
      adrenomedullin belong to a unique group of peptide hormones important for
      homeostasis maintenance. We recently identified intermedin (IMD) as a novel
      member of the calcitonin/calcitonin gene-related peptide family expressed in the
      pituitary, digestive tract, and other organs of vertebrates. Real-time PCR and
      immunohistochemical analysis of pituitaries from rats at different stages of
      development showed that IMD is expressed in the intermediate lobe and select
      adrenocorticotrophs in the anterior lobe, suggesting that IMD could function as a
      paracrine factor regulating anterior pituitary hormone secretion. In support of a
      paracrine role for IMD in the pituitary, quantitative and in situ hybridization
      analyses showed the expression of IMD receptor transcripts including the
      calcitonin receptor-like receptor and receptor activity-modifying proteins in the
      pituitary. Treatment with IMD leads to a dose-dependent increase of prolactin
      release in cultured rat pituitary cells. In contrast, IMD treatment has
      negligible effects on the release of GH, FSH, or ACTH. Likewise, in vivo
      treatment with IMD leads to an elevation of plasma prolactin levels in conscious
      rats. Based on these functional characteristics, we hypothesized that IMD could
      represent one of the intermediate lobe-derived prolactin-releasing factors
      important for prolactin regulation during reproduction. In support of this
      hypothesis, studies of IMD expression in lactating and ovariectomized rats showed
      that pituitary IMD transcripts in lactating animals increased to more than 2-fold
      over nonlactating controls whereas ovariectomy leads to a 90% reduction of IMD
      expression in the pituitary. Of importance, subsequent treatment with 17beta
      estradiol or diethylstilbestrol increased pituitary IMD expression in
      ovariectomized rats. In addition, analysis of the proximate region of the IMD
      gene promoter showed that the IMD gene promoter contains consensus estrogen
      response element sequences, and estrogen treatments up-regulate the promoter
      reporter activity in transfected pituitary cells. Collectively, the present study
      indicates that IMD represents a novel estrogen-dependent intermediate lobe
      derived prolactin-releasing factor and could play important roles in the
      regulation of prolactin release during reproduction in females.

PMID- 16002436
TI  - Fluid volume or arterial pressure, that is the question.

PMID- 16002437
TI  - Coordinated collagen and muscle protein synthesis in human patella tendon and
      quadriceps muscle after exercise.
AB  - We hypothesized that an acute bout of strenuous, non-damaging exercise would
      increase rates of protein synthesis of collagen in tendon and skeletal muscle but
      these would be less than those of muscle myofibrillar and sarcoplasmic proteins.
      Two groups (n = 8 and 6) of healthy young men were studied over 72 h after 1 h of
      one-legged kicking exercise at 67% of maximum workload (W(max)). To label tissue
      proteins in muscle and tendon primed, constant infusions of [1-(13)C]leucine or
      [1-(13)C]valine and flooding doses of [(15)N] or [(13)C]proline were given
      intravenously, with estimation of labelling in target proteins by gas
      chromatography-mass spectrometry. Patellar tendon and quadriceps biopsies were
      taken in exercised and rested legs at 6, 24, 42 or 48 and 72 h after exercise.
      The fractional synthetic rates of all proteins were elevated at 6 h and rose
      rapidly to peak at 24 h post exercise (tendon collagen (0.077% h(-1)), muscle
      collagen (0.054% h(-1)), myofibrillar protein (0.121% h(-1)), and sarcoplasmic
      protein (0.134% h(-1))). The rates decreased toward basal values by 72 h although
      rates of tendon collagen and myofibrillar protein synthesis remained elevated.
      There was no tissue damage of muscle visible on histological evaluation. Neither
      tissue microdialysate nor serum concentrations of IGF-I and IGF binding proteins
      (IGFBP-3 and IGFBP-4) or procollagen type I N-terminal propeptide changed from
      resting values. Thus, there is a rapid increase in collagen synthesis after
      strenuous exercise in human tendon and muscle. The similar time course of changes
      of protein synthetic rates in different cell types supports the idea of
      coordinated musculotendinous adaptation.

PMID- 16002438
TI  - Cerebral blood flow changes associated with fluctuations in alpha and theta
      rhythm during sleep onset in humans.
AB  - Cerebral blood flow (CBF) is typically reduced during stable non-rapid eye
      movement (non-REM) sleep compared with the waking level. It is not known when in
      the sleep cycle these changes occur. However, spontaneous fluctuations in alpha
      and theta rhythm during sleep onset are associated with marked changes in cardio
      respiratory control. The aim of this study was to test the hypothesis that
      changes in CBF would occur during sleep onset and would be related to changes in
      cortical activity. Middle cerebral artery velocity (MCAV) was measured using
      transcranial Doppler ultrasound, as an index of CBF, in 10 healthy subjects.
      Sleep state, ventilation, end tidal carbon dioxide (PET,CO2), arterial oxygen
      saturation (SaO2), mean arterial blood pressure (MABP) and cardiac R-R interval
      (RR) were monitored simultaneously. Immediately following the transition from
      alpha to theta rhythm (the transition from wake to sleep), ventilation decreased
      by 13.4% and tidal volume (VT) by 12.2% (P<0.01); PET,CO2 increased by 1.9%
      (P<0.01); respiratory frequency (fR) and SaO2 did not change significantly. MCAV
      increased by 9.7% (P<0.01); MABP decreased by 3.2% (P<0.01) but RR did not change
      significantly. Immediately following the transition from theta to alpha rhythm
      (spontaneous awakening), increased by 13.3% (P<0.01); VT increased by 11.4%
      (P<0.01); PET,CO2 decreased by 1.9% (P<0.01); MCAV decreased by 11.1% (P<0.01)
      and MABP decreased by 7.5%; fR, SaO2 and RR did not change significantly. These
      changes in MCAV during sleep onset cannot be attributed to changes in ventilation
      or MABP. We speculate that the changes in cerebral vascular tone during sleep
      onset are mediated neurally, by regulatory mechanisms linked to the changes in
      cortical state, and that these mechanisms are different from those regulating the
      longer-term reduction in CBF associated with stable non-REM sleep.

PMID- 16002439
TI  - Virtual head rotation reveals a process of route reconstruction from human
      vestibular signals.
AB  - The vestibular organs can feed perceptual processes that build a picture of our
      route as we move about in the world. However, raw vestibular signals do not
      define the path taken because, during travel, the head can undergo accelerations
      unrelated to the route and also be orientated in any direction to vary the
      signal. This study investigated the computational process by which the brain
      transforms raw vestibular signals for the purpose of route reconstruction. We
      electrically stimulated the vestibular nerves of human subjects to evoke a
      virtual head rotation fixed in skull co-ordinates and measure its perceptual
      effect. The virtual head rotation caused subjects to perceive an illusory whole
      body rotation that was a cyclic function of head-pitch angle. They perceived
      whole-body yaw rotation in one direction with the head pitched forwards, the
      opposite direction with the head pitched backwards, and no rotation with the head
      in an intermediate position. A model based on vector operations and the anatomy
      and firing properties of semicircular canals precisely predicted these
      perceptions. In effect, a neural process computes the vector dot product between
      the craniocentric vestibular vector of head rotation and the gravitational unit
      vector. This computation yields the signal of body rotation in the horizontal
      plane that feeds our perception of the route travelled.

PMID- 16002440
TI  - Protective role of hydrogen peroxide in oxygen-deprived dopaminergic neurones of
      the rat substantia nigra.
AB  - Hydrogen peroxide (H2O2) is a reactive oxygen species, responsible for cytotoxic
      damage through the formation of hydroxyl radicals. Dopamine (DA) neurones of the
      substantia nigra pars compacta (SNc) are highly sensitive to metabolic stress,
      and they typically respond to energy deprivation with membrane hyperpolarization,
      mainly through opening of ATP-dependent K+ channels. Accordingly, H2O2 (3 mM)
      induced a tolbutamide-sensitive outward current in DA neurones. Conversely, in a
      hypoxic medium, H2O2 reverted membrane hyperpolarization, which is associated
      with oxygen deprivation in DA neurones, restored their action potential firing,
      and reduced the hypoxia-mediated outward current in a concentration-dependent
      manner, between 0.1 and 3 mM (IC50 0.6+/-0.1 mM). Notably, H2O2 did not
      counteract membrane hyperpolarization associated with hypoglycaemia, moreover,
      when catalase was inhibited with 3-amino-1,2,4-triazole (3-AT; 30 mM), H2O2 did
      not reduce hypoxia-mediated outward current. The counteracting action of H2O2 on
      hypoxia-mediated effects was further confirmed by single-unit extracellular
      recordings of presumed DA neurones in acute midbrain slices preparations, using a
      planar multi-electrode array device. Whilst a prolonged period of hypoxia (40
      min) caused firing suppression, which did not recover after perfusion in normoxic
      conditions, the presence of H2O2 (3 mM) during this prolonged hypoxic period
      rescued most of the neurones from irreversible firing inhibition. Accordingly,
      morphological studies showed that H2O2 counteracts the cytochrome c release
      provoked by prolonged hypoxic treatment. Taken together, our data suggest that
      H2O2 prevents the metabolic stress of DA neurones induced by hypoxia by serving
      as a supplementary source of molecular oxygen, through its degradation by
      catalase.

PMID- 16002441
TI  - Modulating parameters of excitability during and after transcranial direct
      current stimulation of the human motor cortex.
AB  - Weak transcranial direct current stimulation (tDCS) of the human motor cortex
      results in excitability shifts which occur during and after stimulation. These
      excitability shifts are polarity-specific with anodal tDCS enhancing
      excitability, and cathodal reducing it. To explore the origin of this
      excitability modulation in more detail, we measured the input-output curve and
      motor thresholds as global parameters of cortico-spinal excitability, and
      determined intracortical inhibition and facilitation, as well as facilitatory
      indirect wave (I-wave) interactions. Measurements were performed during short
      term tDCS, which elicits no after-effects, and during other tDCS protocols which
      do elicit short- and long-lasting after-effects. Resting and active motor
      thresholds remained stable during and after tDCS. The slope of the input-output
      curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of
      the primary motor cortex reduced intracortical inhibition and enhanced
      facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation
      during, and additionally increased inhibition after its administration. During
      tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal
      tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects.
      These results suggest that the effect of tDCS on cortico-spinal excitability
      during a short period of stimulation (which does not induce after-effects)
      primarily depends on subthreshold resting membrane potential changes, which are
      able to modulate the input-output curve, but not motor thresholds. In contrast,
      the after-effects of tDCS are due to shifts in intracortical inhibition and
      facilitation, and at least partly also to facilitatory I-wave interaction, which
      is controlled by synaptic activity.

PMID- 16002443
TI  - Zinc inhibits human ClC-1 muscle chloride channel by interacting with its common
      gating mechanism.
AB  - Transition metals block the muscle Cl- channel ClC-1, which belongs to a large
      family of double-barreled Cl- channels and transporters. In the Torpedo Cl-
      channel ClC-0, Zn2+ block is closely related to the common gating mechanism that
      opens and closes both pores of the channel simultaneously, and the mutation
      C212S, which locks the common gate open, also eliminates the block. In ClC-1,
      however, previous results suggested that Zn2+ block is independent of gating, and
      that the cysteine residues involved in Zn2+ binding are in different positions to
      those that confer Zn2+ sensitivity on ClC-0. In this work, we show that Zn2+
      block of ClC-1 is faster at hyperpolarized potentials where the channel is more
      likely to be in the closed state. Mutation C277S, equivalent to C212S in ClC-0,
      which locks the common gate in ClC-1 open, virtually eliminates Zn2+ block. A
      mutation, V321A, which reduces open probability of the common gate, facilitated
      Zn2+ block. These results demonstrate that Zn2+ block is state dependent, acting
      on the common gate. The extent of the block, however, is not a simple function of
      the open probability of the common gate. The Q10 of approximately 13 of the time
      course of Zn2+ block, which is significantly higher than the Q10 of common gating
      transitions in WT ClC-1, suggests that Zn2+ binds to a very high temperature
      dependent low-probability closed substate of the common gate, which has not yet
      been characterized in this channel.

PMID- 16002442
TI  - The GABAergic projection of the dentate gyrus to hippocampal area CA3 of the rat:
      pre- and postsynaptic actions after seizures.
AB  - The glutamatergic granule cells of the dentate gyrus transiently express
      GABAergic markers after seizures. Here we show that when this occurs, their
      activation produces (i) GABA(A) receptor-mediated synaptic field responses in
      CA3, with the physiological and pharmacological characteristics of mossy fibre
      transmission, and (ii) GABA(A) receptor-mediated collateral inhibition. Control
      hippocampal slices present, on stimulation of the dentate gyrus, population
      responses in stratum lucidum, which are blocked by ionotropic glutamate receptor
      antagonists. By contrast, in slices from rats subjected to seizures in vivo,
      dentate activation additionally produces GABA(A) receptor-mediated field synaptic
      responses in the presence of glutamate receptor antagonists. One-dimensional
      current source density analysis confirmed the spatial coincidence of the
      glutamatergic and GABAergic dendritic currents. The GABA(A) receptor-mediated
      field responses show frequency-dependent facilitation and strong inhibition
      during activation of metabotropic glutamate receptors. In the presence of
      glutamate receptor blockers, a conditioning pulse delivered to one site of the
      dentate gyrus inhibits the population synaptic response and the afferent volley
      provoked by the activation of a second site, in a bicuculline-sensitive manner.
      In accordance with this, antidromic responses evoked by mossy fibre activation
      were enhanced by perfusion of bicuculline. Our results suggest that, for GABA
      receptor-dependent field potentials to be detected, a considerable number of
      boutons of a well-defined GABAergic pathway should simultaneously release GABA to
      act on a large number of receptors. Therefore, putative GABA release from the
      mossy fibres acts on pre- and postsynaptic sites to affect hippocampal activity
      at the network level after seizures.

PMID- 16002444
TI  - Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: role
      of ionic changes.
AB  - Muscle damage, characterized by prolonged weakness and delayed onset of stiffness
      and soreness, is common following contractions in which the muscles are
      stretched. Stretch-induced damage of this sort is more pronounced in the muscular
      dystrophies and the profound muscle damage observed in these conditions may
      involve similar pathways. It has been known for many years that damaged muscles
      accumulate calcium and that elevating calcium in normal muscles simulates many
      aspects of muscle damage. The changes in intracellular calcium, sodium and pH
      following stretched contractions are reviewed and the various pathways which have
      been proposed to allow ion entry are discussed. One possibility is that TRPC1
      (transient receptor potential, canonical), a protein which seems to form both a
      stretch-activated channel and a store-operated channel, is the main source of
      Ca(2+) entry. The mechanisms by which the changes in intracellular ions
      contribute to reduced force production, to increased protein breakdown and to
      increased membrane permeability are considered. A hypothetical scheme for muscle
      damage which incorporates these ideas is presented.

PMID- 16002445
TI  - Enhancement of spontaneous synaptic activity in rat Purkinje neurones by ATP
      during development.
AB  - The establishment of functional synaptic connections and activity is a pivotal
      process in the development of neuronal networks. We have studied the synaptic
      activity in the developing rat cerebellum, and the contribution mediated by
      purinergic receptors. The mean frequency of the spontaneous postsynaptic currents
      (sPSCs) recorded with the whole-cell patch-clamp technique from Purkinje neurones
      in acute brain slices at room temperature, increased fourfold from 4.4+/-0.8 Hz
      at postnatal day 9/10 (n=23) to 17.8+/-1.6 Hz at postnatal day 17-20 (p17-p20;
      n=113; P<0.01). ATP, which increased the frequency of sPSCs by up to 100%
      (EC50=18 microM) in the third postnatal week, started to modulate the synaptic
      activity during the second postnatal week, which was determined by three
      processes: (1) the appearance of functional ATP receptors during p10-p12, (2) the
      enhancement of the sPSC frequency by endogenous ATP release becoming apparent
      after inhibition of ecto-ATPases by 6-N,N-diethyl-beta,gamma-dibromomethylene-D
      adenosine-5-triphosphate (ARL67156; 50 microM) at p11-p12, and (3) with tonic
      stimulation of purinoceptors at p14, as revealed by the P2 receptor antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM). ATP
      had a similar effect at later stages (p24-p27) and at 35 degrees C. Our results
      suggest that endogenous release of ATP starts to enhance the synaptic activity in
      Purkinje neurones by the end of the second postnatal week.

PMID- 16002446
TI  - Shortening velocity of human triceps surae muscle measured with the slack test in
      vivo.
AB  - Unloaded shortening velocity (V(0)) of human triceps surae muscle was measured in
      vivo by applying the 'slack test', originally developed for determining V(0) of
      single muscle fibres, to voluntary contractions at varied activation levels
      (ALs). V(0) was measured from 10 subjects at five different ALs defined as a
      fraction (5, 10, 20, 40 and 60%) of the maximum voluntary contraction (MVC)
      torque. Although individual variability was apparent, V(0) tended to increase
      with AL (R(2) = 0.089; P = 0.035) up to 60%MVC (8.6 +/- 2.6 rad s(-1)). This
      value of V(0) at 60%MVC was comparable to the maximum shortening velocity of
      plantar flexors reported in the previous studies. Electromyographic analysis
      showed that the activities of soleus, medial gastrocnemius and lateral
      gastrocnemius muscles increased with AL during isometric contraction and after
      the application of quick release in a similar manner. Also, it showed that the
      activity of an antagonist, tibialis anterior muscle, was negligible, even though
      a slight increase took place after the quick release of agonist. Correlation
      analysis showed that there were no significant correlations between V(0) and MVC
      torque normalized with respect to body mass, although the correlation coefficient
      was relatively high at low ALs. The results suggest that in human muscle, V(0)
      represents the unloaded velocity of the fastest muscle fibres recruited, and
      increases with AL possibly because of progressive recruitment of faster fibres.
      Individual variability may be explained, at least partially, by the difference in
      fibre-type composition.

PMID- 16002447
TI  - Human vagal baroreflex sensitivity fluctuates widely and rhythmically at very low
      frequencies.
AB  - Arterial pressure fluctuates rhythmically in healthy supine resting humans, who,
      from all outward appearances, are in a 'steady-state'. Others have asked, If
      baroreflex mechanisms are functioning normally, how can arterial pressure be so
      variable? We reanalysed data from nine healthy young adult men and women and
      tested the hypotheses that during brief periods of observation, human baroreflex
      sensitivity fluctuates widely and rhythmically. We estimated vagal baroreflex
      sensitivity with systolic pressure and R-R interval cross-spectra measured over
      15 s segments, moved by 2 s steps through 20-min periods of frequency- and tidal
      volume-controlled breathing. We studied each subject at the same time on three
      separate days, with fixed protocols that included two physiological states,
      supine and passive 40 deg upright tilt, before and after beta-adrenergic,
      cholinergic, and angiotensin converting enzyme blockade. Minimum, mean and
      maximum (+/-s.d.) supine control baroreflex sensitivities averaged 5 +/- 3, 18 +/
      6, and 55 +/- 22 ms mmHg(-1). In most subjects, moderate ongoing fluctuations of
      baroreflex sensitivity were punctuated by brief major peaks, yielding frequency
      distributions that were skewed positively. Fast Fourier transforms indicated that
      baroreflex sensitivity fluctuations (expressed as percentages of total power)
      concentrated more in very low, 0.003-0.04 Hz, than ultra low, 0.0-0.003 Hz,
      frequencies (77 +/- 7 versus 11 +/- 8%, P < or = 0.001, rank sum test).
      Autoregressive centre frequencies averaged 0.012 +/- 0.003 Hz. The periodicity of
      very low frequency baroreflex sensitivity fluctuations was not influenced
      significantly by upright tilt, or by variations of autonomic drive or angiotensin
      activity. Our analysis indicates that during ostensibly 'steady-state'
      conditions, human vagal baroreflex sensitivity fluctuates in a major way, at very
      low frequencies.

PMID- 16002448
TI  - Differences in left ventricular long-axis function from mice to humans follow
      allometric scaling to ventricular size.
AB  - While the heart size maintains a constant proportion to body size, heart function
      parameters, such as heart rate and cardiac output, show a more complex scaling
      pattern. How these phenomena affect the long-axis left ventricular (LV) function
      is unknown. We studied 10 mice, 15 rats, 6 rabbits, 8 mongrel dogs and 38 human
      volunteers. Doppler tissue echocardiography data were postprocessed to
      reconstruct mitral annulus (MA) peak systolic velocity and displacement. The
      relationship between MA peak velocity, MA displacement and LV ejection time, and
      LV end-diastolic volume (and mass) were fit to an allometric (power-law) equation
      Y=kMbeta. LV mass varied from 0.062 to 255 g, while end-diastolic volume varied
      from 0.014 to 205 ml. beta values of the relation between LV ejection time and LV
      end-diastolic volume and mass were 0.247+/-0.017 and 0.267+/-0.018, respectively.
      beta values of the relationship between MA displacement and LV end-diastolic
      volume and mass were 0.358+/-0.047 and 0.390+/-0.051 (P<0.023 versus beta of LV
      ejection time). beta values of the relationship between MA peak systolic velocity
      and LV end-diastolic volume and mass were 0.096+/-0.012 and 0.100+/-0.013,
      respectively (P<0.0001 versus 0). Finally, beta values of the relationship
      between the long-to-short axis displacement ratio and LV end-diastolic volume and
      mass were 0.077+/-0.017 and 0.086+/-0.019 (P<0.0001 versus 0). We conclude that
      MA velocity, displacement, and long-to-short axis displacement ratio scale
      allometrically to heart size. This reduces the relative long-axis contribution to
      heart function in small mammals.

PMID- 16002449
TI  - Defining electrical communication in skeletal muscle resistance arteries: a
      computational approach.
AB  - Vascular cells communicate electrically to coordinate their activity and control
      tissue blood flow. To foster a quantitative understanding of this fundamental
      process, we developed a computational model that was structured to mimic a
      skeletal muscle resistance artery. Each endothelial cell and smooth muscle cell
      in our virtual artery was treated as the electrical equivalent of a capacitor
      coupled in parallel with a non-linear resistor representing ionic conductance;
      intercellular gap junctions were represented by ohmic resistors. Simulations
      revealed that the vessel wall is not a syncytium in which electrical stimuli
      spread equally to all constitutive cells. Indeed, electrical signals spread in a
      differential manner among and between endothelial cells and smooth muscle cells
      according to the initial stimulus. The predictions of our model agree with
      physiological data from the feed artery of the hamster retractor muscle. Cell
      orientation and coupling resistance were the principal factors that enable
      electrical signals to spread differentially along and between the two cell types.
      Our computational observations also illustrated how gap junctional coupling
      enables the vessel wall to filter and transform transient electrical events into
      sustained voltage responses. Functionally, differential electrical communication
      would permit discrete regions of smooth muscle activity to locally regulate blood
      flow and the endothelium to coordinate regional changes in tissue perfusion.

PMID- 16002450
TI  - Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+
      current in rat and mouse sensory neurones.
AB  - The tetrodotoxin-resistant (TTX-r) persistent Na(+) current, attributed to
      Na(V)1.9, was recorded in small (< 25 mum apparent diameter) dorsal root ganglion
      (DRG) neurones cultured from P21 rats and from adult wild-type and Na(V)1.8 null
      mice. In conventional whole-cell recordings intracellular GTP-gamma-S caused
      current up-regulation, an effect inhibited by the PKC pseudosubstrate inhibitor,
      PKC19-36. The current amplitude was also up-regulated by 25 microM intracellular
      1-oleoyl-2-acetyl-sn-glycerol (OAG) consistent with PKC involvement. In
      perforated-patch recordings, phorbol 12-myristate 13-acetate (PMA) up-regulated
      the current, whereas membrane-permeant activators of protein kinase A (PKA) were
      without effect. PGE(2) did not acutely up-regulate the current. Conversely, both
      PGE(2) and PKA activation up-regulated the major TTX-r Na(+) current, Na(V)1.8.
      Extracellular ATP up-regulated the persistent current with an average apparent
      K(d) near 13 microM, possibly consistent with P2Y receptor activation. Numerical
      simulation of the up-regulation qualitatively reproduced changes in sensory
      neurone firing properties. The activation of PKC appears to be a necessary step
      in the GTP-dependent up-regulation of persistent Na(+) current.

PMID- 16002451
TI  - No effect of growth hormone administration on substrate oxidation during exercise
      in young, lean men.
AB  - The purpose of this study was to examine the effects of increased fat
      availability induced by growth hormone (GH) administration on the oxidative
      metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/
      S.E.M.); peak oxygen consumption : 62 +/- 1 ml min(-1) kg(-1) (completed four
      randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU
      (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc.
      In all studies a standardized meal was given 2 h after GH or Plc injection. GH
      administration resulted in an approximately 60-fold increase in serum GH
      concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase
      in serum GH was followed by an increase in circulating glycerol at rest (8%, P <
      0.0001). When combined with exercise the increase in plasma glycerol was more
      pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this
      increase in fat mobilization did not increase fat oxidation during exercise
      (indirect calorimetry). In conclusion, GH administration combined with aerobic
      exercise increased lipolytic parameters substantially more than exercise alone,
      but did not further augment whole body fat oxidation.

PMID- 16002452
TI  - Physiological and morphological development of the rat cerebellar Purkinje cell.
AB  - Cerebellar Purkinje cells integrate multimodal afferent inputs and, as the only
      projection neurones of the cerebellar cortex, are key to the coordination of a
      variety of motor- and learning-related behaviours. In the neonatal rat the
      cerebellum is undeveloped, but over the first few postnatal weeks both the
      structure of the cerebellum and cerebellar-dependent behaviours mature rapidly.
      Maturation of Purkinje cell physiology is expected to contribute significantly to
      the development of cerebellar output. However, the ontogeny of the
      electrophysiological properties of the Purkinje cell and its relationship to
      maturation of cell morphology is incompletely understood. To address this problem
      we performed a detailed in vitro electrophysiological analysis of the spontaneous
      and intracellularly evoked intrinsic properties of Purkinje cells obtained from
      postnatal rats (P0 to P90) using whole-cell patch clamp recordings. Cells were
      filled with neurobiotin to enable subsequent morphological comparisons. Three
      stages of physiological and structural development were identified. During the
      early postnatal period (P0 to approximately P9) Purkinje cells were characterized
      by an immature pattern of Na(+)-spike discharge, and possessed only short
      multipolar dendrites. This was followed by a period of rapid maturation (from
      approximately P12 to approximately P18), consisting of changes in Na(+)-spike
      discharge, emergence of repetitive bursts of Na(+) spikes terminated by Ca(2+)
      spikes (Ca(2+)-Na(+) bursts), generation of the trimodal pattern, and a
      significant expansion of the dendritic tree. During the final stage (> P18 to
      P90) there were minor refinements of cell output and a plateau in dendritic area.
      Our results reveal a rapid transition of the Purkinje cell from morphological and
      physiological immaturity to adult characteristics over a short developmental
      window, with a close correspondence between changes in cell output and dendritic
      growth. The development of Purkinje cell intrinsic electrophysiological
      properties further matches the time course of other measures of cerebellar
      structural and functional maturation.

PMID- 16002453
TI  - Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of
      residues in the region that follows TM1 in the ectodomain of the channel.
AB  - The acid-sensitive ion channel 1 (ASIC1) is a neuronal Na+ channel insensitive to
      changes in membrane potential but is gated by external protons. Proton
      sensitivity is believed to be essential for the role of ASIC1 in modulating
      synaptic transmission and nociception in the mammalian nervous system. To examine
      the structural determinants that confer proton sensitivity, we cloned and
      functionally characterized ASIC1 from different species of the chordate lineage:
      lamprey, shark, toadfish and chicken. We observed that ASIC1s from early
      vertebrates (lamprey and shark) were proton insensitive in spite of a high degree
      of amino acid conservation (66-67%) with their mammalian counterparts. Sequence
      analysis showed that proton-sensitive ASIC1s could not be distinguished from
      proton-insensitive channels by any signature in the protein sequence. Chimeras
      made with rat ASIC1 (rASIC1) and lamprey or shark indicated that most of the
      ectodomain of rASIC1 was required to confer proton sensitivity and the distinct
      kinetics of activation and desensitization of the rat channel. Proton-sensitive
      chimeras contained the segment D78-E136, together with residues D351, Q358 and
      E359 of the rat sequence. However, none of the functional chimeras containing
      only part of the rat extracellular domain retained the kinetics of activation and
      desensitization of rASIC1, suggesting that residues distributed in several
      regions of the ectodomain contribute to allosteric changes underlying activation
      and desensitization. The results also demonstrate that gating by protons is not a
      feature common to all ASIC1 channels. Proton sensitivity arose recently in
      evolution, implying that agonists different from protons activate ASIC1 in lower
      vertebrates.

PMID- 16002454
TI  - Factors mediating powerful voltage attenuation along CA1 pyramidal neuron
      dendrites.
AB  - We performed simultaneous patch-electrode recordings from the soma and apical
      dendrite of CA1 pyramidal neurons in hippocampal slices, in order to determine
      the degree of voltage attenuation along CA1 dendrites. Fifty per cent attenuation
      of steady-state somatic voltage changes occurred at a distance of 238 microm from
      the soma in control and 409 microm after blocking the hyperpolarization-activated
      (H) conductance. The morphology of three neurons was reconstructed and used to
      generate computer models, which were adjusted to fit the somatic and dendritic
      voltage responses. These models identify several factors contributing to the
      voltage attenuation along CA1 dendrites, including high axial cytoplasmic
      resistivity, low membrane resistivity, and large H conductance. In most cells the
      resting membrane conductances, including the H conductances, were larger in the
      dendrites than the soma. Simulations suggest that synaptic potentials attenuate
      enormously as they propagate from the dendrite to the soma, with greater than 100
      fold attenuation for synapses on many small, distal dendrites. A prediction of
      this powerful EPSP attenuation is that distal synaptic inputs are likely only to
      be effective in the presence of conductance scaling, dendritic excitability, or
      both.

PMID- 16002455
TI  - Influences of blood sample processing on low-molecular-weight proteome identified
      by surface-enhanced laser desorption/ionization mass spectrometry.
AB  - BACKGROUND: Profiling approaches in proteomics, such as surface-enhanced laser
      desorption/ionization (SELDI) mass spectrometry, are used in disease marker
      discovery. The aim of this study was to investigate the potential influence of
      selected preanalytical factors on the results obtained. METHODS: Plasma samples
      anticoagulated with EDTA, citrate, or heparin, and serum samples from healthy
      volunteers were profiled by SELDI on CM10, immobilized metal affinity capture
      (IMAC) array with copper, and H50 chip surfaces. Using linear mixed-effects
      models, we examined the influence of elapsed time between venipuncture and sample
      separation (immediate to 24 h) and the type of serum tube used (Greiner Vacuette
      activator, gel serum separator, or plain tubes). We analyzed purified platelets,
      as well as platelet-poor and platelet-rich plasma samples treated with calcium
      and/or thrombin to determine the platelet contribution, directly or via the
      clotting process, to the profiles generated. We then used cluster analysis to
      identify samples with similar peak profiles. RESULTS: Different plasma types and
      sera could be distinguished on the basis of cluster analyses of their spectral
      profiles. Elapsed time between venipuncture and separation of plasma and serum
      from blood samples altered the profiles obtained, particularly for serum samples
      and particularly on IMAC chips. The type of serum collection tube also affected
      the profiles because of differences in clotting time. In vitro manipulation of
      platelets revealed that specific peaks in IMAC profiles of serum appeared to be
      derived directly from platelets. Several other peaks, including some of those
      exhibiting time-dependent changes, arose during the clotting process. CONCLUSION:
      Preanalytical variables, such as sample handling, can markedly influence results.

PMID- 16002456
TI  - Immunoquantitative PCR for prion protein detection in sporadic Creutzfeldt-Jakob
      disease.
AB  - BACKGROUND: The most common human prion disorder is Creutzfeldt-Jakob disease
      (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes.
      Diagnostic tests aim at detection with the highest specificity of very small
      deposits of abnormal prion protein (PrP). METHODS: We used immunoquantitative PCR
      (iqPCR) to detect proteinase K-resistant PrP (PrPRes) in tissue from the middle
      frontal gyrus of 7 patients with sporadic CJD and 7 non-CJD cases. We compared
      iqPCR with routine optimized ELISA, Western blotting, and immunohistochemical
      analyses. RESULTS: The 4 methods showed similar 100% sensitivity and specificity
      for the diagnosis of CJD. Along with high specificity, however, iqPCR had a
      threshold for PrP(Res) detection at least 10-fold lower than that of the classic
      ELISA. CONCLUSIONS: iqPCR is a new method for PrPRes detection that combines 100%
      specificity with a detection threshold at least 10-fold lower than classic
      techniques. This method may improve the detection of minute PrPRes deposits in
      tissues and body fluids and thus be useful for diagnostic and sterilization
      applications.

PMID- 16002457
TI  - Immunoprecipitation for rapid detection of macroprolactin in the form of
      prolactin-immunoglobulin complexes.

PMID- 16002458
TI  - The effect of CYP2E1-dependent oxidant stress on activity of proteasomes in HepG2
      cells.
AB  - A reduction in proteasome activity and accumulation of oxidized proteins may play
      a role in alcoholic liver disease. The current study assessed proteasome
      peptidase activities and oxidative modifications of proteasomes during oxidative
      stress generated by CYP2E1. The model of toxicity by arachidonic acid (AA) and
      iron [ferric-nitrilotriacetate (Fe-NTA)] in HepG2 cells overexpressing CYP2E1
      (E47 cells) and control C34 cells was used. AA/Fe-NTA treatment decreased trypsin
      like (T-L) activity of the proteasome in E47 cells but not in C34 cells. This
      inhibition was abolished by antioxidants. Chymotrypsin-like activity of the
      proteasome was increased in E47 cells, and activity was not altered by AA/Fe-NTA
      treatment. There were no changes in content of subunits of 20S proteasomes or 19S
      regulator ATPase subunits S4 and p42 by AA/Fe-NTA treatment. An increased content
      of the PA28alpha subunit of the 11S regulator of proteasomes was detected in E47
      cells. In proteasome pellets, the decline of T-L activity was accompanied by
      increased content of carbonyl adducts, suggesting oxidative modification of
      proteasomes. Higher levels of ubiquitinated, 3-nitrotyrosine- and 4
      hydroxynonenal-modified proteins and lower levels of free ubiquitin were detected
      in untreated E47 cells in comparison with C34 cells. Accumulation of protein
      cross-linked, detergent-insoluble aggregates was increased with AA/Fe-NTA
      treatment in E47 cells. Thus, reactive oxygen species generated upon CYP2E1
      dependent oxidative stress mediated a decline in T-L proteasome function,
      increased carbonyl adducts in proteasomes, and promoted protein aggregate
      formation; this may alter the balance among protein oxidation, ubiquitination,
      and degradation.

PMID- 16002459
TI  - Persistent binding and functional antagonism by xanomeline at the muscarinic M5
      receptor.
AB  - Xanomeline is a functionally selective M1/M4 muscarinic acetylcholine receptor
      agonist. We have previously identified a novel mode of interaction of this ligand
      with the muscarinic M1 receptor that involves persistent binding and activation
      of the receptor after extensive washout. In the present study, we tested the
      hypothesis that xanomeline also binds in a wash-resistant manner to muscarinic
      receptor subtypes where it exhibits low or no efficacy, such as the M5 receptor
      subtype. A secondary hypothesis is that persistent binding of xanomeline to the
      M5 receptor results in wash-resistant antagonism to the effects of full agonists.
      These hypotheses were tested in Chinese hamster ovary cells stably expressing the
      M5 receptor. In these cells, xanomeline is a weak partial agonist and is able to
      inhibit carbachol-induced phosphoinositide hydrolysis to the maximal response of
      xanomeline in a concentration-dependent manner. Pretreatment with xanomeline
      followed by extensive washing resulted in a significant wash-resistant reduction
      in receptor affinity with no significant change in maximal cell surface receptor
      density. This was associated with wash-resistant antagonism of carbachol-induced
      activation of phosphoinositide hydrolysis at the M5 receptor, reflected as
      decreased carbachol potency without a change in the maximal response. Similar
      experiments using the partial agonist pilocarpine demonstrated a reduction of
      pilocarpine potency as well as maximal response. Our results clearly indicate
      that wash-resistant binding of xanomeline to the muscarinic M5 receptor is
      accompanied by persistent antagonism of receptor function. They also suggest a
      relationship between the efficacy of xanomeline and the functional consequences
      of its wash-resistant binding at different muscarinic receptor subtypes.

PMID- 16002460
TI  - Pressor responses to ephedrine are mediated by a direct mechanism in the rat.
AB  - The mechanism of the pressor response to ephedrine is controversial. In the
      present study. i.v. injections of ephedrine increased systemic and pulmonary
      arterial pressure, and i.a. injections decreased hindlimb blood flow in a dose
      related manner. Responses to ephedrine were inhibited by alpha-receptor blocking
      agents and were not attenuated by blockade of the norepinephrine reuptake
      transporter (NET) or by catecholamine depletion using reserpine or a combination
      of reserpine and alpha-methyl-p-tyrosine, whereas responses to tyramine and
      amphetamine were inhibited by these treatments. The magnitude of the pressor
      response to ephedrine was similar in anesthetized and conscious rats.
      Tachyphylaxis developed to pressor responses to ephedrine and amphetamine with
      sequential injections; however, ephedrine tachyphylaxis differed in that
      subsequent responses to alpha-receptor agonists were attenuated. These results
      suggest that the systemic and pulmonary pressor and hindlimb vasoconstrictor
      responses to ephedrine are mediated by direct action on alpha-adrenergic
      receptors and that the release of norepinephrine from adrenergic terminals plays
      no significant role. These results provide support for the hypothesis that
      responses to ephedrine are directly mediated in the intact rat, whereas responses
      to amphetamine are mediated in a large part by the release of norepinephrine from
      adrenergic terminals.

PMID- 16002461
TI  - Progress toward acetate supplementation therapy for Canavan disease: glyceryl
      triacetate administration increases acetate, but not N-acetylaspartate, levels in
      brain.
AB  - Canavan disease (CD) is a fatal genetic neurodegenerative disorder caused by
      mutations in the gene for aspartoacylase, an enzyme that hydrolyzes N
      acetylaspartate (NAA) into L-aspartate and acetate. Because aspartoacylase is
      localized in oligodendrocytes, and NAA-derived acetate is incorporated into
      myelin lipids, we hypothesize that an acetate deficiency in oligodendrocytes is
      responsible for the pathology in CD, and we propose acetate supplementation as a
      possible therapy. In our preclinical efforts toward this goal, we studied the
      effectiveness of orally administered glyceryl triacetate (GTA) and calcium
      acetate for increasing acetate levels in the murine brain. The concentrations of
      brain acetate and NAA were determined simultaneously after intragastric
      administration of GTA. We found that the acetate levels in brain were increased
      in a dose- and time-dependent manner, with a 17-fold increase observed at 1 to 2
      h in 20- to 21-day-old mice at a dose of 5.8 g/kg GTA. NAA levels in the brain
      were not significantly increased under these conditions. Studies using mice at
      varying stages of development showed that the dose of GTA required to maintain
      similarly elevated acetate levels in the brain increased with age. Also, GTA was
      significantly more effective as an acetate source than calcium acetate. Chronic
      administration of GTA up to 25 days of age did not result in any overt pathology
      in the mice. Based on these results and the current Food and Drug Administration
      approved use of GTA as a food additive, we propose that it is a potential
      candidate for use in acetate supplementation therapy for CD.

PMID- 16002462
TI  - The role of protein kinase C isoforms in modulating injury and repair of the
      intestinal barrier.
AB  - Gastrointestinal cells express a diverse group of protein kinase C (PKC) isoforms
      that play critical roles in a number of cell functions, including intracellular
      signaling and barrier integrity. PKC isoforms expressed by gastrointestinal
      epithelial cells consist of three major PKC subfamilies: conventional isoforms
      (alpha, beta1, beta2, and gamma), novel isoforms (delta, epsilon, theta, eta, and
      mu), and atypical isoforms (lambda, tau, and zeta). This review highlights recent
      discoveries, including our own, that some PKC isoforms in gastrointestinal
      epithelia monolayer cell culture are involved in injury to, whereas others are
      involved in protection of, intestinal barrier integrity. For example, certain PKC
      isoforms aggravate oxidative damage, whereas others protect against it. These
      findings suggest that the development of agents that selectively activate or
      inhibit specific PKC isoforms may lead to new therapeutic modalities for
      important gastrointestinal disorders such as cancer and inflammatory bowel
      disease.

PMID- 16002463
TI  - Role of tyrosine kinase inhibitors in cancer therapy.
AB  - Cancer chemotherapy has been one of the major medical advances in the last few
      decades. However, the drugs used for this therapy have a narrow therapeutic
      index, and often the responses produced are only just palliative as well as
      unpredictable. In contrast, targeted therapy that has been introduced in recent
      years is directed against cancer-specific molecules and signaling pathways and
      thus has more limited nonspecific toxicities. Tyrosine kinases are an especially
      important target because they play an important role in the modulation of growth
      factor signaling. This review focuses on small molecule inhibitors of tyrosine
      kinase. They compete with the ATP binding site of the catalytic domain of several
      oncogenic tyrosine kinases. They are orally active, small molecules that have a
      favorable safety profile and can be easily combined with other forms of
      chemotherapy or radiation therapy. Several tyrosine kinase inhibitors (TKIs) have
      been found to have effective antitumor activity and have been approved or are in
      clinical trials. The inhibitors discussed in this manuscript are imatinib
      mesylate (STI571; Gleevec), gefitinib (Iressa), erlotinib (OSI-1774; Tarceva),
      lapatinib (GW-572016), canertinib (CI-1033), semaxinib (SU5416), vatalanib
      (PTK787/ZK222584), sorafenib (BAY 43-9006), sutent (SU11248), and leflunomide
      (SU101). TKIs are thus an important new class of targeted therapy that interfere
      with specific cell signaling pathways and thus allow target-specific therapy for
      selected malignancies. The pharmacological properties and anticancer activities
      of these inhibitors are discussed in this review. Use of these targeted therapies
      is not without limitations such as the development of resistance and the lack of
      tumor response in the general population. The availability of newer inhibitors
      and improved patient selection will help overcome these problems in the future.

PMID- 16002464
TI  - Histones are required for transcription of yeast rRNA genes by RNA polymerase I.
AB  - Nucleosomes and their histone components have generally been recognized to act
      negatively on transcription. However, purified upstream activating factor (UAF),
      a transcription initiation factor required for RNA polymerase (Pol) I
      transcription in Saccharomyces cerevisiae, contains histones H3 and H4 and four
      nonhistone protein subunits. Other studies have shown that histones H3 and H4 are
      associated with actively transcribed rRNA genes. To examine their functional role
      in Pol I transcription, we constructed yeast strains in which synthesis of H3 is
      achieved from the glucose-repressible GAL10 promoter. We found that partial
      depletion of H3 (approximately 50% depletion) resulted in a strong inhibition
      (>80%) of Pol I transcription. A combination of biochemical analysis and electron
      microscopic (EM) analysis of Miller chromatin spreads indicated that initiation
      and elongation steps and rRNA processing were compromised upon histone depletion.
      A clear decrease in relative amounts of UAF, presumably caused by reduced
      stability, was also observed under the conditions of H3 depletion. Therefore, the
      observed inhibition of initiation can be explained, in part, by the decrease in
      UAF concentration. In addition, the EM results suggested that the defects in rRNA
      transcript elongation and processing may be a result of loss of histones from
      rRNA genes rather than (or in addition to) an indirect consequence of effects of
      histone depletion on expression of other genes. Thus, these results show
      functional importance of histones associated with actively transcribed rRNA
      genes.

PMID- 16002465
TI  - Genetic interactions between [PSI+] and nonstop mRNA decay affect phenotypic
      variation.
AB  - Yeast strains can reversibly interconvert between [PSI+] and [psi-] states. The
      [PSI+] state is caused by a prion form of the translation termination factor
      eRF3. The [PSI+] state causes read-through at stop codons and can lead to
      phenotypic variation, although the molecular mechanisms causing those phenotypic
      changes remain unknown. We identify an interaction between [PSI+]-induced
      phenotypic variation and defects in nonstop mRNA decay. Nonstop mRNA decay is
      triggered when a ribosome reaches the 3' end of the transcript. In contrast, we
      observed little interaction between [PSI+]-induced phenotypic variation and
      defects in nonsense-mediated decay, which lead to suppression of premature stop
      codons. These results suggest that at least some of the phenotypic effects of
      [PSI+] may be due to read-through of "normal" stop codons, thereby producing
      extended proteins. Moreover, these observations suggest that nonstop mRNA decay
      may limit [PSI+]-induced phenotypic variation. Such a process would allow
      periodic sampling of the 3' UTR, which can diverge rapidly, for novel and
      beneficial protein extensions.

PMID- 16002466
TI  - Identification of mammalian arginyltransferases that modify a specific subset of
      protein substrates.
AB  - Posttranslational N-terminal protein arginylation, mediated by Arg-tRNA-protein
      transferase 1 (ATE1), is essential for cardiovascular development and
      angiogenesis in mammals but is nonessential in yeast. Evidence suggests that many
      proteins are arginylated in vivo in both mammals and yeast; however, in yeast, N
      terminal arginylation can occur only on proteins bearing an N-terminal Asp or
      Glu, whereas in mammals, N-terminal Cys residues are also arginylation targets,
      suggesting that Cys arginylation contributes to the essential role of ATE1 in
      mammals. To date, all of the characterized forms of ATE1 in yeast and mammals
      have been shown to arginylate only Asp and Glu, leaving open to speculation
      whether Cys arginylation is possible only through other components of mammalian
      arginylation machinery and whether Cys-specific forms of Arg-transferase exist in
      mammals. Here, we report the identification of two forms of Arg-transferase in
      mice that are specific for N-terminal Cys. We also show that the two previously
      identified mammalian forms of ATE1 can arginylate Cys-containing substrates in
      addition to Asp- and Glu-containing substrates. This finding provides insights
      into the significance of Cys-specific protein arginylation in mammals and
      suggests possibilities of the determinants of substrate specificity within the
      ATE1 molecule.

PMID- 16002467
TI  - SyrB2 in syringomycin E biosynthesis is a nonheme FeII alpha-ketoglutarate- and
      O2-dependent halogenase.
AB  - The nine-residue lipodepsipeptide syringomycin E, elaborated as a phytotoxin by
      Pseudomonas syringae pv. syringae B301D contains a 4-Cl-L-Thr-9 moiety where
      failure to chlorinate results in a 3-fold drop in biological activity. The
      proteins SyrB1 and SyrB2 encoded by the biosynthetic cluster are shown to act as
      a substrate and enzyme pair for SyrB2-mediated chlorination of the aminoacyl-S
      enzyme L-Thr-S-SyrB1. SyrB2 is a member of the nonheme Fe(II) alpha-ketoglutarate
      dependent enzyme superfamily, and requires O2 and alpha-ketoglutarate as well as
      chloride ion to carry out monochlorination of the -CH3 group of L-Thr-S-SyrB1.
      Chlorination of L-Thr-S-SyrB1 was validated by thioesterase-mediated release of L
      Thr and 4-Cl-L-Thr, N-derivatization as fluorescent isoindoles, and HPLC
      separation compared with authentic standards. Incubations with L-[14C]Thr and
      [36Cl-] as well as MS of the released products further validated identification.
      Enzymatic oxidative halogenation is a previously uncharacterized reaction type
      for nonheme Fe(II) enzymes and may be the general mode for biosynthetic
      halogenation of aliphatic carbons of natural products.

PMID- 16002468
TI  - The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex.
AB  - Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in
      all kingdoms of life. In addition, fungi possess a specialized Hsp70 system
      attached to ribosomes, which in Saccharomyces cerevisiae consists of the Hsp70
      homologs Ssb1/2p, Ssz1p, and the Hsp40 homolog zuotin. Ssz1p and zuotin are
      assembled into a unique heterodimeric complex termed ribosome-associated complex.
      So far, no such specialized chaperones have been identified on ribosomes of
      higher eukaryotes. However, a family of proteins characterized by an N-terminal
      zuotin-homology domain fused to a C-terminal two-repeat Myb domain is present in
      animals and plants. Members of this family, like human MPP11 and mouse MIDA1,
      have been implicated in the regulation of cell growth. Specific targets of
      MPP11/MIDA1, however, have remained elusive. Here, we report that MPP11 is
      localized to the cytosol and associates with ribosomes. Purification of MPP11
      revealed that it forms a stable complex with Hsp70L1, a distantly related homolog
      of Ssz1p. Complementation experiments indicate that mammalian ribosome-associated
      complex is functional in yeast. We conclude that despite a low degree of homology
      on the amino acid level cooperation of ribosome-associated chaperones with the
      translational apparatus is well conserved in eukaryotic cells.

PMID- 16002469
TI  - Altered axonal architecture by removal of the heavily phosphorylated
      neurofilament tail domains strongly slows superoxide dismutase 1 mutant-mediated
      ALS.
AB  - Eliminating assembled neurofilaments (NFs) from axons or misaccumulating NFs in
      motor neuron cell bodies strongly slows disease in mouse models of mutant
      superoxide dismutase 1 (SOD1)-induced amyotrophic lateral sclerosis. One proposal
      for how reducing axonal NFs can increase survival is that the multiphosphorylated
      tail domains of the two larger NF subunits act in motor neuron cell bodies as
      phosphorylation sinks where they mitigate cyclin-dependent kinase 5 dysregulation
      induced by mutant SOD1. Elimination by gene targeting in mice of the NF medium
      and NF heavy tail domains and their 58 known phosphorylation sites accelerates
      aberrant phosphorylation of other neuronal substrates while leaving overall NF
      content unaltered. However, disease onset is significantly delayed and survival
      is extended, inconsistent with the ameliorative property of altered NF content
      protecting by serving as substrates for dysregulation of any NF kinase. Moreover,
      at comparable disease stages significantly more surviving motor neurons and axons
      were found in SOD1 mutant mice deleted in the NF tails than in similar mice with
      wild-type NFs. This finding supports noncell autonomous toxicity in SOD1 mutant
      mediated amyotrophic lateral sclerosis: removal of the NF tails slows damage
      developed directly within motor neurons, but SOD1 mutant damage within
      nonneuronal supporting cells reduces motor neuron functionality.

PMID- 16002470
TI  - Adult mouse brain gene expression patterns bear an embryologic imprint.
AB  - The current model to explain the organization of the mammalian nervous system is
      based on studies of anatomy, embryology, and evolution. To further investigate
      the molecular organization of the adult mammalian brain, we have built a gene
      expression-based brain map. We measured gene expression patterns for 24 neural
      tissues covering the mouse central nervous system and found, surprisingly, that
      the adult brain bears a transcriptional "imprint" consistent with both
      embryological origins and classic evolutionary relationships. Embryonic cellular
      position along the anterior-posterior axis of the neural tube was shown to be
      closely associated with, and possibly a determinant of, the gene expression
      patterns in adult structures. We also observed a significant number of embryonic
      patterning and homeobox genes with region-specific expression in the adult
      nervous system. The relationships between global expression patterns for
      different anatomical regions and the nature of the observed region-specific genes
      suggest that the adult brain retains a degree of overall gene expression
      established during embryogenesis that is important for regional specificity and
      the functional relationships between regions in the adult. The complete
      collection of extensively annotated gene expression data along with data mining
      and visualization tools have been made available on a publicly accessible web
      site (www.barlow-lockhart-brainmapnimhgrant.org).

PMID- 16002471
TI  - Single-cell Raman and fluorescence microscopy reveal the association of lipid
      bodies with phagosomes in leukocytes.
AB  - Cellular imaging techniques based on vibrational spectroscopy have become
      powerful tools in cell biology because the molecular composition of subcellular
      compartments can be visualized without the need for labeling. Using high
      resolution, nonresonant confocal Raman microscopy on individual cells, we
      demonstrate here that lipid bodies (LBs) rich in arachidonate as revealed by
      their Raman spectra associate with latex bead-containing phagosomes in
      neutrophilic granulocytes. This finding was corroborated in macrophages and in
      PLB-985 cells, which can be induced to differentiate into neutrophil-like cells,
      by selective staining of LBs and visualization by confocal fluorescence
      microscopy. We further show that the accumulation of LBs near phagosomes is
      mediated at least in part by the flavohemoprotein gp91phox (in which "phox" is
      phagocyte oxidase), because different LB distributions around phagocytosed latex
      beads were observed in WT and gp91phox-deficient PLB-985 cells. gp91phox, which
      accumulates in the phagosomal membrane, is the catalytic subunit of the leukocyte
      NADPH oxidase, a critical enzyme in the innate immune response. Finally, time
      lapse fluorescence microscopy experiments on neutrophils revealed that the LB
      phagosome association is transient, similar to the "kiss-and-run" behavior
      displayed by endosomes involved in phagosome maturation. Because arachidonic acid
      (AA) has been shown to be involved in NADPH oxidase activation and phagosome
      maturation in neutrophils and macrophages, respectively, the findings reported
      here suggest that LBs may provide a reservoir of AA for local activation of these
      essential leukocyte functions.

PMID- 16002472
TI  - Parkin negatively regulates JNK pathway in the dopaminergic neurons of
      Drosophila.
AB  - Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal
      recessive juvenile parkinsonism characterized primarily by selective loss of
      dopaminergic neurons with subsequent defects in movements. However, the molecular
      mechanisms underlying this neuron loss remain elusive. Here, we characterized
      Drosophila parkin loss-of-function mutants, which exhibit shrinkage of
      dopaminergic neurons with decreased tyrosine hydroxylase level and impaired
      locomotion. The behavioral defect of parkin mutant flies was partially restored
      by administering L-DOPA, and the dopamine level in the brains of parkin mutant
      flies was highly decreased. Intriguingly, we found that c-Jun N-terminal kinase
      (JNK) is strongly activated in the dopaminergic neurons of parkin mutants and
      that impaired dopaminergic neuron phenotypes are dependent on the activation of
      the JNK signaling pathway. In consistent with this, our epistatic analysis and
      mammalian cell studies showed that Parkin inhibits the JNK signaling pathway in
      an E3 activity-dependent manner. These results suggest that loss of Parkin
      function up-regulates the JNK signaling pathway, which may contribute to the
      vulnerability of dopaminergic neurons in Drosophila parkin mutants and perhaps
      autosomal recessive juvenile parkinsonism patients.

PMID- 16002474
TI  - Restoring atomic configuration at interfaces by image deconvolution.
AB  - The image deconvolution technique in combination with dynamical scattering effect
      correction developed previously for crystal defect investigation has been
      modified to meet the needs of interface studies and applied to a [111] twin model
      of Si. Elliptical windows are utilized as a new means for Fourier filtering and
      correcting the amplitudes of reflections. Images were simulated with a 200 kV
      field-emission high-resolution electron microscope. After image restoration, four
      images simulated with different defocus values were transformed into structure
      images with atomic columns revealed individually at correct positions. The
      effectiveness of the technique is discussed.

PMID- 16002473
TI  - Replication and packaging of Norwalk virus RNA in cultured mammalian cells.
AB  - Human noroviruses, the most common cause of nonbacterial gastroenteritis, are
      characterized by high infectivity rate, low infectious dose, and unusually high
      stability outside the host. However, human norovirus research is hindered by the
      lack of a cell culture system and a small animal model of infection. Norwalk
      virus (NV) is the prototype strain of human noroviruses. We report here
      replication of NV viral RNA and its packaging into virus particles in mammalian
      cells by intracellular expression of native forms of NV viral RNA devoid of
      extraneous nucleotide sequences derived from the expression vector by the use of
      replication-deficient vaccinia virus MVA encoding the bacteriophage T7 RNA
      polymerase (MVA/T7). Expressed genomic RNA was found to replicate; NV subgenomic
      RNA was transcribed from genomic RNA by use of NV nonstructural proteins
      expressed from genomic RNA and was subsequently translated into NV capsid protein
      VP1. Viral genomic RNA was packaged into virus particles generated in mammalian
      cells. The cesium chloride (CsCl) density gradient profile of virus particles
      containing genomic RNA was similar to that of NV purified from stool. These
      observations indicate that the NV cDNA constructed here is a biologically
      infectious clone, and that mammalian cells have the ability to replicate NV
      genomic RNA. This work establishes a mammalian cell-based system for analysis of
      human norovirus replication and, thus, makes it feasible to investigate antiviral
      agents in mammalian cells.

PMID- 16002476
TI  - Validation and development of a predictive paradigm for hemotoxicology using a
      multifunctional bioluminescence colony-forming proliferation assay.
AB  - The lympho-hematopoietic colony-forming assay has been redesigned into a rapid,
      nonsubjective and standardized proliferation assay that can measure the effects
      of compounds on multiple stem and progenitor cell populations from different
      species simultaneously using a sensitive, high-throughput bioluminescence
      readout. Eleven reference compounds from the Registry of Cytotoxicity (RC) and
      eight other compounds, including anticancer drugs, were studied over an 8- to 9
      log dose range for their effects on seven cell populations from both human and
      mouse bone marrow simultaneously. The cell populations studied included a
      primitive (HPP-SP) and mature (CFC-GEMM) stem cell, three hematopoietic (BFU-E,
      GM-CFC, Mk-CFC) and two lymphopoietic (T-CFC, B-CFC) populations. The results
      reveal a five-point prediction paradigm for lympho-hematotoxicity. Depending on
      how and which populations are affected, the resulting effects in the periphery
      can be predicted. Validation against the RC Prediction Model produces a high
      degree of correlation between the in vitro IC(50) values and known in vivo LD(50)
      values, thereby allowing preclinical dosing to be predicted. If primary human
      hematopoietic target tissue is used, inhibitory concentration
      (IC(50)/IC(75)/IC(90)) values of anticancer and other drugs can be converted into
      predicted clinical doses which, when compared to published chemotherapeutic
      dosing regimen, are very similar. When performed during early drug screening, the
      prediction value of the assay should help reduce time and cost, but above all,
      provide increase efficacy and safety for the patient.

PMID- 16002475
TI  - Induction of fibroblast growth factor-9 and interleukin-1alpha gene expression by
      motorcycle exhaust particulate extracts and benzo(a)pyrene in human lung
      adenocarcinoma cells.
AB  - Motorcycle exhaust particulates (MEP) contain carcinogenic polycyclic aromatic
      hydrocarbons including benzo(a)pyrene. This study has determined the ability of
      MEP to alter the expression of select genes from drug metabolism, cytokine,
      oncogene, tumor suppressor, and estrogen signaling families of human lung
      adenocarcinoma CL5 cells. cDNA microarray analyses and confirmation studies were
      performed using CL5 cells treated with 100 microg/ml MEP extract for 6 h. The
      results showed that MEP increased the mRNA levels of metabolic enzymes CYP1A1 and
      CYP1B1, proinflammatory cytokines interleukin (IL)-1alpha, IL-6, and IL-11,
      fibroblast growth factor (FGF)-6 and FGF-9, vascular endothelial growth factor
      (VEGF)-D, oncogene fra-1, and tumor suppressor p21. In contrast, MEP decreased
      tumor suppressor Rb mRNA in CL5 lung epithelial cells. Treatment with 10 microM
      benzo(a)pyrene for 6 h altered gene expression profiles, in a manner similar to
      those by MEP. Induction of IL-1alpha, IL-6, IL-11, and FGF-9 mRNA by MEP and
      benzo(a)pyrene was concentration and time dependent. Cotreatment with 2 mM N
      acetylcysteine blocked the MEP- and benzo(a)pyrene-mediated induction. Treatment
      with MEP or benzo(a)pyrene increased IL-6 and IL-11 releases to CL5 cell medium.
      Incubation of human lung fibroblast WI-38 with MEP- or benzo(a)pyrene-induced CL5
      conditioned medium for 4 days stimulated cell growth of the fibroblasts.
      Inhalation exposure of rats to 1:10 diluted motorcycle exhaust 2 h daily for 4
      weeks increased CYP1A1, FGF-9, and IL-1alpha mRNA in lung. This present study
      shows that MEP and benzo(a)pyrene can induce metabolic enzyme, inflammatory
      cytokine, and growth factor gene expression in CL5 cells and stimulate lung
      epithelium-fibroblast interaction.

PMID- 16002477
TI  - Prediction of 2-year carcinogenicity study results for pharmaceutical products:
      how are we doing?
AB  - Some have proposed that 2-year carcinogenicity studies may not be necessary if
      the material is a direct-acting DNA mutagen, induces liver enzymes, causes
      hyperplasia or toxicity in particular organs, causes cell proliferation, is
      cytotoxic, causes hormonal perturbations, or if one has QSAR analyses or 'omics
      information. Safety pharmacology data, pharmacologic activity, metabolism data,
      and results of 13-week dose ranging studies (with organ weight data, clinical
      chemistry data, hematologic data, clinical signs and histopathologic findings)
      were compared with results of 2-year carcinogenicity studies reviewed by the
      Center for Drug Evaluation and Research (CDER)/FDA. The experience with the ICH
      genetic toxicology battery and alternative carcinogenicity models was also
      reviewed. It appears that the information available from short-term studies is
      not currently sufficient to accurately and reliably predict the outcome of long
      term carcinogenicity studies.

PMID- 16002478
TI  - An integrated addition and interaction model for assessing toxicity of chemical
      mixtures.
AB  - The high propensity for simultaneous exposure to multiple environmental chemicals
      necessitates the development and use of models that provide insight into the
      toxicity of chemical mixtures. In this study, we developed a mathematical model
      that combines concepts of concentration addition, response addition, and
      toxicokinetic chemical interaction to assess toxicity of chemical mixtures. A
      ternary mixture of acetylcholinesterase inhibiting organophosphates (malathion
      and parathion) and the P450 inhibitor piperonyl butoxide was used to model
      toxicity. Concentration-response curves were generated for individual chemicals
      as well as for mixtures of the chemicals using acute toxicity tests with Daphnia
      magna. The toxicity of binary combinations of malathion and parathion adhered to
      the principles of concentration addition. The contribution of piperonyl butoxide
      to mixture toxicity was integrated using a model for response addition. Piperonyl
      butoxide also modified the toxicity of the organophosphates by inhibiting their
      metabolic activation. The antagonistic effects of piperonyl butoxide towards the
      organophosphates were quantified as coefficients of interactions (K-functions)
      and incorporated into the mixture model. Finally, toxicity of the ternary mixture
      was modeled at 30 different mixture formulations using three additive models that
      assumed no interaction (concentration addition, response addition, and integrated
      addition) and using the integrated addition and interaction (IAI) model. Toxicity
      of the 30 mixtures was then experimentally determined and compared to model
      results. Only the IAI model accurately predicted the toxicity of the mixtures.
      The IAI model holds promise as a means for assessing hazard of complex chemical
      mixtures.

PMID- 16002479
TI  - Progress towards development of an amphibian-based thyroid screening assay using
      Xenopus laevis. Organismal and thyroidal responses to the model compounds 6
      propylthiouracil, methimazole, and thyroxine.
AB  - In response to the initial Endocrine Disruptor Screening and Testing Advisory
      Committee (EDSTAC) recommendations, research was conducted on the development of
      a Xenopus laevis based tail resorption assay for evaluating thyroid axis
      disruption. This research highlighted key limitations associated with relying on
      tail resorption as a measure of anti/thyroid activity. The most critical
      limitation being that tail tissues of tadpoles at metamorphic climax are
      insensitive to perturbation by thyroid axis agonists/antagonists. To improve upon
      the initial proposal, we have conducted experiments comparing the sensitivity of
      pre-metamorphic (stage 51) and pro-metamorphic (stage 54) larvae to the model
      thyroid axis disruptors methimazole (control, 6.25, 12.5, 25, 50, 100 mg/l), 6
      propylthiouracil (PTU) (control, 1.25, 2.5, 5, 10, and 20 mg/l), and thyroxine
      (T4) (0.25, 0.5, 1, 2, 4 microg/l). Exposures were conducted using two different
      experimental designs. For experimental design 1, tadpoles were exposed to
      methimazole or PTU starting at either NF stage 51 or NF 54 for 14 days. For
      experimental design 2, tadpoles were exposed to PTU or T4 starting at NF stage 51
      or NF 54 for 14 and 21 days, respectively. Methimazole and PTU, which are thyroid
      hormone synthesis inhibitors, both caused a concentration dependent delay in
      larval development. As determined from this endpoint, there were only minor
      differences in sensitivity observed among the two stages examined. Further, both
      compounds caused concentration dependent changes in thyroid gland morphology.
      These changes were characterized as reduced colloid, glandular hypertrophy, and
      cellular hyperplasia and hypertrophy. Treatment failed to negatively affect
      growth, even in tadpoles that experienced significant metamorphic inhibition. T4
      treatment resulted in a concentration dependent increase in developmental rate,
      as would be expected. Similar to studies with methimazole, there were no
      differences in sensitivity among the two developmental stages examined. These
      results indicate that tadpoles in the early stages of metamorphosis are sensitive
      to thyroid axis disruption and that development of a short-term, diagnostic
      amphibian-based thyroid screening assay shows considerable promise.

PMID- 16002480
TI  - Associations of paternal involvement in disease management with maternal and
      family outcomes in families with children with chronic illness.
AB  - OBJECTIVE: The role of fathers in pediatric disease management and its
      associations with family functioning have rarely been the focus of empirical
      study. In this study, we used the Dads Active Disease Support scale (DADS), a
      measure of the amount and helpfulness of paternal involvement in pediatric
      disease management, to explore the association between father involvement and
      other aspects of family functioning. METHOD: A sample of 190 heterosexual couples
      completed the DADS and measures of maternal, marital, and family functioning.
      RESULTS: Maternal report of higher ratings on DADS Helpfulness scale was
      associated with fewer self-reported maternal psychiatric symptoms and less
      perceived impact of the disease on family functioning. Both mothers' and fathers'
      reports indicated that more paternal involvement was related to more favorable
      outcomes in marital satisfaction and family functioning. CONCLUSIONS: More
      paternal involvement in disease management was associated with healthier
      maternal, marital, and family functioning. Longitudinal studies are needed to
      determine whether paternal involvement is likely to be a fruitful target for
      psychological intervention.

PMID- 16002481
TI  - Paternal involvement in the management of pediatric chronic diseases:
      associations with adherence, quality of life, and health status.
AB  - OBJECTIVES: This article reports associations among paternal involvement in
      pediatric chronic disease management and child outcomes. METHODS: The Dads'
      Active Disease Support scale (DADS) and measures of treatment adherence, quality
      of life, health status, and health care utilization were obtained for youths with
      six chronic diseases, with complete data sets obtained from 190 couples. RESULTS:
      Paternal involvement was not associated with these outcomes among younger
      children. Among adolescents, mother-reported and father-reported DADS scores
      indicating more paternal involvement were associated with maintenance, rather
      than deterioration, of treatment adherence and more favorable quality of life.
      Youths' health status and health care utilization were not related significantly
      to paternal involvement. CONCLUSIONS: More paternal involvement was associated
      with more favorable adherence and quality of life among adolescents but not
      associated with health status or health care utilization. Longitudinal studies
      could verify whether paternal involvement merits clinical intervention.

PMID- 16002482
TI  - Smoking during pregnancy: association with childhood temperament, behavior, and
      academic performance.
AB  - OBJECTIVE: This study investigated the association between maternal smoking
      during pregnancy and ratings of offspring's temperament, behavior, and academic
      performance at various developmental periods in childhood. METHODS: Multivariate
      analyses of a birth cohort examined the outcomes for children on measures of
      temperament, behavior, and academic performance in infancy (6 months), at age 5,
      and at age 12. RESULTS: When controlling for maternal psychiatric
      hospitalization, psychological distress during pregnancy, hospitalization for
      accidents, socioeconomic status, age, and symptoms of upper respiratory infection
      and nausea, a range of associations between maternal smoking and child outcomes
      were observed at different ages studied. CONCLUSION: Despite widespread warning
      regarding smoking cessation during pregnancy, the literature base on the longer
      term effects beyond the neonatal and infant period is less available. This is one
      of the first studies to investigate the association between maternal smoking
      during pregnancy and child outcomes at several stages of development. The results
      provide evidence for the lasting effects of smoking during pregnancy on the
      development of the child.

PMID- 16002483
TI  - Prevalence and variance of shoulder injuries in elite collegiate football
      players.
AB  - BACKGROUND: Shoulder injuries are the fourth most common musculoskeletal injury
      encountered in American football players. There is little information in the
      literature on the role of playing position in the type of shoulder injuries seen.
      HYPOTHESIS: There is a high prevalence of shoulder injuries in elite collegiate
      American football players, with type of injury varying by playing position. STUDY
      DESIGN: Cohort study (prevalence); Level of evidence, 3. METHODS: A total of 336
      elite collegiate American football players were invited to the National Football
      League Combine for physical testing and medical evaluation. Current and
      historical data were evaluated for the purpose of this study, and all players
      underwent radiographic examinations, including plain radiographs and/or magnetic
      resonance imaging when necessary. All shoulder pathological conditions and
      shoulder surgical procedures were recorded. Players were categorized by position
      for the analysis of position-specific trends. RESULTS: Of the players, 50% had a
      history of shoulder injuries, with a total of 226 shoulder injuries (1.3 injuries
      per player injured); 56 players (34%) had a total of 73 surgeries. The most
      common injuries were acromioclavicular separation (41%), anterior instability
      (20%), rotator cuff injury (12%), clavicle fracture (4%), and posterior
      instability (4%). The most common surgeries performed were anterior instability
      reconstruction (48%), Mumford/Weaver-Dunn surgery (15%), posterior instability
      surgery (10%), and rotator cuff surgery (10%). Shoulder injuries were more common
      in quarterbacks and defensive backs. Surgery was more common in linebackers or
      linemen. A history of anterior instability was more common in defensive players,
      with surgery required 76% of the time. Linemen had more rotator cuff injuries and
      posterior instability than players in other positions. CONCLUSION: Shoulder
      injuries are common injuries in elite collegiate football players, with one-third
      undergoing surgical procedures. There are definitive trends in the types of
      injuries per player position.

PMID- 16002484
TI  - First rib stress fractures in throwing athletes.

PMID- 16002485
TI  - The effect of estradiol and progesterone on knee and ankle joint laxity.
AB  - BACKGROUND: Female athletes suffer a higher incidence of anterior cruciate
      ligament injuries compared to their male counterparts, and they appear to be at
      increased risk for these injuries when they have increased anterior-posterior
      knee laxity and at specific phases of the menstrual cycle. Although the mechanism
      by which these factors combine to increase injury risk is unclear, studies
      suggest that cyclic variations in joint laxity produced by hormone fluctuation
      during the menstrual cycle predispose an athlete to increased risk of ligamentous
      injury. Little is known about whether joint laxity varies cyclically during the
      menstrual cycle and if so, whether it is modulated by cyclic variations of
      estradiol (E2) and progesterone (P4). HYPOTHESIS: Increased serum estradiol (E2)
      and progesterone (P4) levels are associated with increased ankle and knee joint
      laxity. STUDY DESIGN: Cohort study. Level of evidence, 2. METHODS: Ankle laxity,
      anterior-posterior knee laxity, and serum concentrations of estradiol (E2) and
      progesterone (P4) were measured during the menstrual cycle in women and at
      corresponding time intervals in men (controls). Ankle laxity was measured from
      stress radiographs and included anterior talar translation relative to the tibia
      and talar tilt relative to the tibia; anterior-posterior knee laxity was measured
      with the KT-1000 arthrometer. RESULTS: Women had greater knee and ankle laxity
      values compared to men. There was, however, no change in knee and ankle laxity
      over the normal menstrual cycle in women and no change over time in men. There
      was no relationship between estradiol and progesterone fluctuation and ankle and
      knee joint laxity. CONCLUSIONS: Knee and ankle joint laxities are greater for
      women compared to men; however, the cyclic estradiol and progesterone
      fluctuations that occur during the menstrual cycle do not produce cyclic
      fluctuations of joint laxity. Studies using joint laxity to identify a subject at
      risk for ligamentous injury need only consider making measurements at a specific
      point in time, such as during a preseason screening evaluation.

PMID- 16002486
TI  - Functional outcome and health-related quality of life after surgical repair of
      full-thickness rotator cuff tear using a mini-open technique.
AB  - BACKGROUND: Rotator cuff tear, a common shoulder injury, can lead to shoulder
      pain and functional loss. HYPOTHESIS: Surgical repair of full-thickness rotator
      cuff tears using the mini-open surgical technique will improve shoulder function
      and health-related quality of life. STUDY DESIGN: Cohort study. Level of
      evidence, 2. METHODS: Patients with a full-thickness rotator cuff tear who
      underwent a mini-open repair were evaluated for (1) active shoulder range of
      motion preoperatively, and 6 months and 12 months postoperatively and (2) health
      related quality of life preoperatively, 6 months postoperatively, and annually up
      to 5 years postoperatively. Satisfaction with the repair and return to work
      status were ascertained 1 year postoperatively. A subgroup analysis of tear size
      and patient age was also undertaken. RESULTS: Of the subjects, 61 (73%) were men,
      and the average age was 53.2 ( +/- 9.9) years. According to repeated-measures
      analysis of variance, shoulder range of motion (flexion and external rotation)
      improved significantly from before surgery to 1 year after surgery (P <.001). The
      mean American Shoulder and Elbow Surgeons scores improved from 53.3 ( +/- 20.6)
      preoperatively to 90.6 ( +/- 11.7) 1 year postoperatively (P <.001). The mean
      Western Ontario Rotator Cuff scores also improved from 43.2 ( +/- 20.2)
      preoperatively to 87.2 ( +/- 14.3) 1 year postoperatively (P <.001). No
      differences were seen in either the American Shoulder and Elbow Surgeons scores
      or Western Ontario Rotator Cuff scores between the 1-year examination and the
      last follow-up assessment undertaken at a median of 5 years postoperatively (P
      >.05). Ninety-six percent of patients were satisfied or very satisfied with the
      results of their repair; 78% of patients who were working before surgery returned
      to work without modification by 1 year postoperatively. For the most part,
      patient age and size of tear did not influence postoperative range of motion or
      health-related quality of life. CONCLUSION: Mini-open rotator cuff repair led to
      improved shoulder function and health-related quality of life up to 5 years
      postoperatively.

PMID- 16002487
TI  - A 7-year follow-up of patellar tendon and hamstring tendon grafts for
      arthroscopic anterior cruciate ligament reconstruction: differences and
      similarities.
AB  - BACKGROUND: For arthroscopic anterior cruciate ligament reconstruction, the most
      commonly used graft constructs are either the hamstring tendon or patellar
      tendon. Well-controlled, long-term studies are needed to determine the
      differences between the 2 materials. HYPOTHESIS: There is a difference between
      hamstring and patellar tendon grafts in the clinical results of anterior cruciate
      ligament reconstructions at 7 years. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: Two groups of 90 patients each, consecutively treated with
      hamstring or patellar tendon grafts, were followed and assessed at 1, 2, 5, and 7
      years after surgery. RESULTS: At the 7-year review, abnormal radiographic
      findings were seen in 45% (24/53) of the patellar tendon group and in 14% (7/51)
      of the hamstring tendon group (P = .002). Although there was no significant
      difference between the groups in extension deficit (P = .22), the percentage of
      patients with an extension deficit increased significantly in the patellar tendon
      group from 8% at 1 year to 25% at 7 years (P = .02). No significant change was
      seen in the hamstring tendon group over time (P = .20). There was no significant
      difference in laxity between the groups on Lachman (P = .44), pivot-shift (P =
      .39), or instrumented (P = .44) testing. Graft rupture occurred in 4 patients
      from the patellar tendon group and in 9 patients from the hamstring tendon group
      (P = .15). Both autografts gave excellent subjective results, as evidenced by the
      International Knee Documentation Committee evaluation and Lysholm knee scores at
      7 years. CONCLUSIONS: Both hamstring and patellar tendon grafts provided good
      subjective outcomes and objective stability at 7 years. No significant
      differences in the rate of graft rupture or contralateral anterior cruciate
      ligament rupture were identified. Patients with patellar tendon grafts had a
      greater prevalence of osteoarthritis at 7 years after surgery; therefore, the
      authors preferred hamstring tendons as the primary graft choice in anterior
      cruciate ligament reconstructions.

PMID- 16002488
TI  - Mechanical properties of the posterolateral structures of the knee.
AB  - BACKGROUND: The individual biomechanical strength properties of the fibular
      collateral ligament, popliteofibular ligament, and popliteus tendon have not been
      well elucidated by previous studies. To define the necessary strength
      requirements for a posterolateral knee reconstruction, these properties for the
      main individual structures of the posterolateral knee need to be defined.
      HYPOTHESIS: The biomechanical failure properties of the fibular collateral
      ligament, popliteofibular ligament, and popliteus tendon can be determined by
      cadaveric testing. STUDY DESIGN: Descriptive laboratory study. METHODS: Each
      structure was individually isolated in 8 fresh-frozen, nonpaired cadaveric knees
      and loaded to failure at more than 100%/s. RESULTS: The mean ultimate tensile
      strength of the fibular collateral ligament was 295 N, the popliteofibular
      ligament was 298 N, and the popliteus tendon was 700 N. The mean cross-sectional
      areas of these same structures at their midpoints were 11.9 mm2, 17.1 mm2, and
      21.9 mm2, respectively. Although the stiffness of the fibular collateral ligament
      (33.5 N/m) was similar to that of the popliteofibular ligament (28.6 N/m), the
      popliteus tendon was significantly stiffer than both (83.7 N/m). CONCLUSION: The
      popliteofibular ligament, fibular collateral ligament, and popliteus tendon can
      resist fairly large loads before failure. Knowledge of the strengths of the main
      native posterolateral knee stabilizers will assist with reconstructive graft
      choices for these structures.

PMID- 16002489
TI  - Correlation of range of motion and glenohumeral translation in professional
      baseball pitchers.
AB  - BACKGROUND: Altered mobility patterns in the throwing shoulders of professional
      baseball pitchers have been reported. Most published reports examining
      glenohumeral laxity have not used an objective testing device. OBJECTIVE:
      Quantify and compare glenohumeral translation and rotational range of motion
      between the throwing and non-throwing shoulders in professional baseball
      pitchers. STUDY DESIGN: Descriptive laboratory study. METHODS: Force-displacement
      and range of motion measures were performed bilaterally on 43 asymptomatic
      professional baseball pitchers. Ultrasound imaging was used to measure
      glenohumeral translations under stressed and unstressed conditions. RESULTS: No
      significant difference in translation was found between the throwing and
      nonthrowing shoulders. For both shoulders, posterior translation (5.38 +/- 2.7
      mm) was significantly greater (P < .001) than was anterior translation (2.81 +/-
      1.6 mm). External rotation in the throwing shoulder was significantly greater
      than that in the nonthrowing shoulder (P < .001), whereas internal rotation in
      the throwing shoulder was significantly less than that in the nonthrowing
      shoulder (P < .001). The total arc of rotation for the throwing shoulder was not
      significantly different than that for the nonthrowing shoulder, and correlation
      coefficients were poor between rotational and translational range of motion in
      the throwing shoulder, ranging from r = 0.232 to 0.209 between variables.
      CONCLUSION: No significant difference in glenohumeral translation exists between
      the throwing and nonthrowing shoulders in asymptomatic professional baseball
      pitchers, posterior translation is significantly greater than anterior
      translation in the throwing shoulders of professional baseball pitchers, and
      glenohumeral translation is not related to rotational range of motion in the
      throwing shoulders of professional baseball pitchers. CLINICAL RELEVANCE: Altered
      mobility patterns in asymptomatic professional baseball pitchers may be due to
      factors other than capsular adaptive changes.

PMID- 16002490
TI  - Hamstring tendon versus patellar tendon anterior cruciate ligament reconstruction
      using biodegradable interference fit fixation: a prospective matched-group
      analysis.
AB  - BACKGROUND: There are still controversies about graft selection for primary
      anterior cruciate ligament reconstruction, especially with respect to knee
      stability and functional outcome. HYPOTHESIS: Biodegradable interference screw
      fixation of hamstring tendon grafts provides clinical results similar to those
      achieved with identical fixation of bone-patellar tendon-bone grafts. STUDY
      DESIGN: Cohort study; Level of evidence, 2. METHODS: In 1996 and 1997, primary
      isolated anterior cruciate ligament reconstruction using a bone-patellar tendon
      bone autograft was performed in 72 patients. Since 1998, hamstring tendons were
      used as routine grafts. Matched patients with a hamstring tendon graft were
      selected from a database (n = 284). All patients were followed prospectively for
      a minimum of 2 years with KT-1000 arthrometer testing, International Knee
      Documentation Committee score, and Lysholm score. RESULTS: In the bone-patellar
      tendon-bone group, 9 patients were excluded because of bilateral rupture of the
      anterior cruciate ligament, 3 patients (4.2%) had a graft rupture, and 4 patients
      were lost to follow-up (follow-up rate, 92.1%), leaving 56 patients for a matched
      group analysis. In the hamstring tendon database, the graft rupture rate was 5.6%
      (P = .698). The Lysholm score was 89.7 in the patellar tendon group and 94 in the
      hamstring tendon group (P = .003). The KT-1000 arthrometer side-to-side
      difference was 2.6 mm for the patellar tendon group and 2.1 mm for the hamstring
      tendon group (P = .041). There were significantly less positive pivot-shift test
      results in the hamstring tendon group (P = .005), and hamstring tendon patients
      showed lower thigh atrophy (P = .024) and patellofemoral crepitus (P = .003).
      Overall International Knee Documentation Committee scores were better (P = .001)
      in the hamstring tendon group (hamstring tendon: 34 x A, 21 x B, 0 x C, 0 x D;
      bone-patellar tendon-bone: 17 x A, 32 x B, 6 x C, 0 x D). CONCLUSIONS: In this
      comparison of anterior cruciate ligament reconstruction with bone-patellar tendon
      bone and anatomical hamstring tendon grafts, the hamstring tendon graft was
      superior in knee stability and function. These findings are partially contrary to
      previous studies and might be attributable to the use of an anatomical joint line
      fixation for hamstring tendon grafts. Thus, hamstring tendons are the authors'
      primary graft choice for anterior cruciate ligament reconstruction, even in high
      level athletes.

PMID- 16002491
TI  - Medial collateral ligament reconstruction using autogenous hamstring tendons:
      technique and results in initial cases.
AB  - BACKGROUND: Although various surgical procedures that attempt to restore the
      function of the medial collateral ligament have been reported, none have achieved
      consistently satisfactory results. HYPOTHESIS: Our reconstructive procedure using
      autogenous semitendinosus and gracilis tendons yields improved results compared
      with conventional procedures. STUDY DESIGN: Case series. Level of evidence, 4.
      METHOD: In our surgical procedure, autogenous semitendinosus and gracilis tendons
      were used to anatomically reconstruct the anterior longitudinal component of the
      superficial medial collateral ligament. From April 1995 through December 2000, 27
      patients with symptomatic medial instability underwent this surgical procedure.
      The majority of the subjects were diagnosed with combined cruciate ligament
      injuries, necessitating concomitant cruciate ligament reconstructions. Of these
      27 patients, 24 were evaluated after a minimum period of 2 years, with a mean
      follow-up period of 27 months (range, 24-48 months). RESULTS: At follow-up,
      medial stability, as well as postoperative range of motion in all patients, was
      graded as normal or nearly normal according to the International Knee
      Documentation Committee evaluation system. No significant postoperative
      complications were encountered. CONCLUSION: Although this is a short-term follow
      up study involving a small number of cases, we considered our procedure to be an
      effective method of surgically restoring the function of the medial collateral
      ligament.

PMID- 16002492
TI  - Extracorporeal shock wave therapy in the treatment of calcific tendinitis of the
      rotator cuff.
AB  - BACKGROUND: Low-energy extracorporeal shock wave therapy is an alternative
      treatment, with limited evidence for effectiveness, for calcific tendinitis of
      the rotator cuff. HYPOTHESIS: Objective localization of the calcium deposit by 3
      dimensional, computer-assisted navigation reveals superior clinical and
      radiographic outcomes compared to localization through patient-to-therapist
      feedback. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence,
      1. METHODS: A prospective, randomized, single-blind study was carried out on 50
      patients. The population was divided into 2 groups of equal numbers (navigation
      group and feedback group). In all patients, treatment-resistant pain was evident
      for longer than 6 months. A total of 3 therapy sessions of constant low-energy
      focused shock wave therapy was administered in weekly intervals in both groups.
      Local anesthesia was not applied. Radiographs and clinical assessment, including
      the Constant and Murley shoulder scoring system and the visual analog scale for
      pain, were performed both before therapy and after 12 weeks. In the navigation
      group, the calcium deposit was localized using a radiographically guided, 3
      dimensional, computer-assisted device. The feedback group was treated after
      locating the point of maximum tenderness through palpation by the therapist with
      feedback from the patient. RESULTS: Both groups had significant improvements in
      the Constant and Murley score and the visual analog scale after 12 weeks. The
      results from the navigation group were statistically significantly superior to
      those of the feedback group. In the navigation group, 6 calcium deposits
      disappeared and 9 altered, compared to 1 disappearance and 12 alterations in the
      feedback group. No severe complications occurred. CONCLUSION: Three-dimensional,
      computer-assisted navigation reveals significantly better results and is
      therefore recommended when extracorporeal shock wave therapy is used in the
      treatment of calcific tendinitis of the rotator cuff.

PMID- 16002493
TI  - Comparison of home versus physical therapy-supervised rehabilitation programs
      after anterior cruciate ligament reconstruction: a randomized clinical trial.
AB  - BACKGROUND: Because of health care funding and policy changes, there is a need to
      examine the effects of an evolution toward patient-directed (ie, home-based)
      rehabilitation programs on clinical outcomes of patients undergoing anterior
      cruciate ligament reconstruction. HYPOTHESIS: There will be no difference in the
      effectiveness of a home-based rehabilitation program and a standard physical
      therapy-supervised rehabilitation program in patients 3 months after nonacute
      anterior cruciate ligament reconstruction with bone-patellar tendon-bone grafts.
      STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1.
      METHODS: There were 145 patients (16-59 years) who attended a presurgery
      education class. Home-based patients attended 4 physical therapy sessions, and
      physical therapy-supervised patients attended 17 physical therapy sessions over
      the first 12 weeks after surgery. All patients followed the same standardized
      rehabilitation program. Study outcome measures included active-assisted knee
      flexion and passive knee extension range of motion, knee range of motion during
      walking, KT computerized arthrometer results, and isokinetic quadriceps and
      hamstrings strength. Patient outcomes were dichotomized as either clinically
      acceptable or unacceptable. Rehabilitation programs were compared by the
      proportion of acceptable patients in each group. RESULTS: The home-based group
      had a significantly higher percentage of patients with acceptable flexion and
      extension range of motion compared to the standard physical therapy group
      (flexion, 67% vs 47%; extension, 97% vs 83%). There were no significant
      differences between the groups in range of motion during walking, ligament
      laxity, and strength. CONCLUSION: A structured, minimally supervised
      rehabilitation program was more effective in achieving acceptable knee range of
      motion in the first 3 months after anterior cruciate ligament reconstruction than
      a standard physical therapy-based program. CLINICAL RELEVANCE: Recreational
      athletes undergoing nonacute anterior cruciate ligament reconstruction can
      successfully reach acceptable rehabilitation goals in the first 3 months after
      surgery with a limited number of purposeful physical therapy education sessions,
      allowing recreational athletes more flexibility when integrating the necessary
      postoperative rehabilitation into their daily activities.

PMID- 16002494
TI  - The resisted supination external rotation test: a new test for the diagnosis of
      superior labral anterior posterior lesions.
AB  - PURPOSE: To evaluate a new clinical test, the resisted supination external
      rotation test, for the diagnosis of superior labral anterior posterior lesions of
      the shoulder. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
      METHODS: Forty athletes (average age, 23.9 years) with activity-related shoulder
      pain were enrolled in the study. The patients underwent 3 different tests
      designed specifically to detect superior labral anterior posterior lesions (the
      resisted supination external rotation test, the crank test, and the active
      compression test); the tests were performed in a random order on the affected
      shoulder. The results of the tests were compared with arthroscopic findings.
      RESULTS: Out of 40 athletes, 29 (72.5%) had superior labral anterior posterior
      tears. The resisted supination external rotation test had the highest sensitivity
      (82.8%), specificity (81.8%), positive predictive value (92.3%), negative
      predictive value (64.3%), and diagnostic accuracy (82.5%) of all tests performed.
      CONCLUSION: By re-creating the peel-back mechanism, the resisted supination
      external rotation test is more accurate than 2 other commonly used physical
      examination tests designed to diagnose superior labral anterior posterior tears
      in overhead-throwing athletes. By using this test in the context of a thorough
      clinical history and physical examination, lesions of the superior labrum can be
      more reliably diagnosed.

PMID- 16002495
TI  - Age and gender effects on lower extremity kinematics of youth soccer players in a
      stop-jump task.
AB  - BACKGROUND: Gender differences in lower extremity motion patterns were previously
      identified as a possible risk factor for non-contact anterior cruciate ligament
      injuries in sports. HYPOTHESIS: Gender differences in lower extremity kinematics
      in the stop-jump task are functions of age for youth soccer players between 11
      and 16 years of age. STUDY DESIGN: Descriptive laboratory study. METHODS: Three
      dimensional videographic data were collected for 30 male and 30 female adolescent
      soccer players between 11 and 16 years of age performing a stop-jump task. The
      age effects on hip and knee joint angular motions were compared between genders
      using multiple regression analyses with dummy variables. RESULTS: Gender and age
      have significant interaction effects on standing height (P = .00), body mass (P =
      .00), knee flexion angle at initial foot contact with the ground (P = .00),
      maximum knee flexion angle (P = .00), knee valgus-varus angle (P = .00), knee
      valgus-varus motion (P = .00), and hip flexion angle at initial foot contact with
      the ground (P = .00). CONCLUSION: Youth female recreational soccer players have
      decreased knee and hip flexion angles at initial ground contact and decreased
      knee and hip flexion motions during the landing of the stop-jump task compared to
      those of their male counterparts. These gender differences in knee and hip
      flexion motion patterns of youth recreational soccer players occur after 12 years
      of age and increase with age before 16 years. CLINICAL RELEVANCE: The results of
      this study provide significant information for research on the prevention of
      noncontact anterior cruciate ligament injuries.

PMID- 16002496
TI  - Revision surgery for failed thermal capsulorrhaphy.
AB  - BACKGROUND: With the failure of thermal capsulorrhaphy for shoulder instability,
      there have been concerns with capsular thinning and capsular necrosis affecting
      revision surgery. PURPOSE: To report the findings at revision surgery for failed
      thermal capsulorrhaphy and to evaluate the technical effects on subsequent
      revision capsular plication. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Fourteen patients underwent arthroscopic evaluation and open
      reconstruction for a failed thermal capsulorrhaphy. The cause of the failure, the
      quality of the capsule, and the ability to suture the capsule were recorded. The
      patients were evaluated at follow-up for failure, which was defined as recurrent
      subluxations or dislocations. RESULTS: The origin of the instability was
      traumatic (n = 6) or atraumatic (n = 8). At revision surgery in the traumatic
      group, 4 patients sustained failure of the Bankart repair with capsular laxity,
      and the others experienced capsular laxity alone. In the atraumatic group, all
      patients experienced capsular laxity as the cause of failure. Of the 14 patients,
      the capsule quality was judged to be thin in 5 patients and ablated in 1 patient.
      A glenoid-based capsular shift could be accomplished in all 14 patients. At
      follow-up (mean, 35.4 months; range, 22 to 48 months), 1 patient underwent
      revision surgery and 1 patient had a subluxation, resulting in a failure rate of
      14%. CONCLUSIONS: Recurrent capsular laxity after failed thermal capsular
      shrinkage is common and frequently associated with capsular thinning. In most
      instances, the capsule quality does not appear to technically affect the revision
      procedure.

PMID- 16002497
TI  - Microvascular angioadaptation after endurance training with L-arginine
      supplementation in rat heart and hindleg muscles.
AB  - This study was designed to examine whether dietary L-arginine supplementation
      modulates exercise-induced angiogenesis and vascular endothelial growth factor
      (VEGF) expression in female Wistar rats. Exercise training (running) lasted for 6
      weeks at 25 m min-1 on a 20% gradient for 10-60 min day-1. Rats in the L-arginine
      treated groups drank water containing 4% L-arginine. Histochemical identification
      of capillary profiles showed that training with L-arginine significantly
      increased the capillary/fibre (C/F) ratio in the subendocardium of the left
      ventricle, whereas training alone did not. Because of a significantly higher
      fibre cross-sectional area, a concomitant, but not significant, decrease in
      capillary density was also observed. In the hindleg muscles, training with L
      arginine significantly increased the C:F ratio, although the degree of change was
      the same as that observed after training alone. Western blot analysis showed that
      training with L-arginine significantly increased VEGF protein expression by 1.7
      fold in the left ventricle, while the increase with training alone was
      insignificant. In the soleus muscle, although VEGF protein expression was
      elevated insignificantly after training (2.8-fold), training with L-arginine
      significantly increased the protein levels (3.8-fold). Tissue endothelial nitric
      oxide synthase protein levels did not changed after either training or L-arginine
      treatment. The present results suggest that L-arginine supplementation causes
      additional effects on exercise-induced angiogenesis in the rat heart by promoting
      VEGF expression.

PMID- 16002498
TI  - Local transfer of prostaglandin E2 into the ovary and its retrograde transfer
      into the uterus in early pregnant sows.
AB  - This study was designed to establish (a) whether prostaglandin E2 (PGE2) can
      reach the ovary and oviduct by a local pathway and what is the contribution of
      lymphatic vessels to this transfer, and (b) whether PGE2 can permeate from venous
      and lymphatic vessels of the mesometrium to arterial blood and be delivered to
      the uterine horn during maternal recognition of pregnancy in gilts. The
      reproductive tract was excised from gilts (n = 10) on day 14 after mating. The
      uterine horn was isolated with the ovary and broad ligament and perfused with
      warmed and oxygenated autologous blood. A total dose of 5.5 x 10(7)
      disintegrations per min (d.p.m.) (49 ng) [3H]PGE2 was infused into the small
      branches of the uterine vein on the broad ligament or into the lymphatic vessels.
      Frequent blood samples were collected from the branch of the uterine artery and
      from the venous effluent. Tissue samples were collected from the uterine horn,
      the ovary and the broad ligament. The concentration of [3H]PGE2 was significantly
      higher in the ovary (P < 0.001), oviduct (P < 0.01), endometrium (P < 0.01),
      myometrium (P < 0.001) and mesometrium (P < 0.001) after infusion of [3H]PGE2
      into lymphatic vessels than into the branches of the uterine vein. In contrast,
      the concentration of [3H]PGE2 was significantly higher in arterial blood
      supplying the uterine horn (P < 0.01) and in the venous effluent (P < 0.001)
      after infusion of [3H]PGE2 into the branches of the uterine vein than into
      lymphatic vessels. These results demonstrated local transfer of [3H]PGE2 into the
      ovary, oviduct and uterine horn from lymphatic and venous vessels of the
      mesometrium. However, the efficiency of this transfer was considerably higher
      after infusion into lymphatic vessels than into branches of the ovarian vein. We
      conclude that the lymphatic pathway is a fundamental mechanism in the local
      transfer of PGE2 from the uterus to the ovary and oviduct during early pregnancy
      in the pig.

PMID- 16002499
TI  - 2005 Dr. Gary J. Becker Young Investigator Award: periprocedural oral
      administration of the leflunomide analogue FK778 inhibits neointima formation in
      a double-injury rat model of restenosis.
AB  - PURPOSE: To test the efficacy of limited oral administration of the new
      leflunomide analogue FK778 for suppression of neointima proliferation in a double
      injury restenosis model in the rat. MATERIALS AND METHODS: For induction of
      aortic lesions, silicon cuffs were placed operatively around the infrarenal
      aortas of Lewis rats. After 21 days, the aortic cuffs were removed and the
      lesions were dilated with 2-F Fogarty catheters inserted via the left common
      carotid artery. The novel immunosuppressant FK778 was administered at a dose of 5
      mg/kg body weight (group 1) or 15 mg/kg body weight (group 2) in a total of 38
      animals. For both doses, three different periinterventional time periods, each
      with a 5-day course of oral FK778, were defined as follows: (i) days -2 to 2,
      (ii) days 1-5, and (iii) days 7-11, with six or seven rats in each group. After 3
      weeks, intima/media ratios were assessed morphometrically and
      immunohistochemistry for quantification of intimal alpha-actin expression was
      performed. RESULTS: In both dose groups, there was a trend toward inhibition of
      neointima formation when the 5-day course of FK778 was started before or 1 day
      after the intervention. However, in the lower-dose group, inhibition of neointima
      was not statistically significant regardless of the time frame of treatment
      (groups 1a-c). With the higher dose, suppression of intimal hyperplasia was
      significant when FK778 was administered between days 1 and 5 after angioplasty
      (group 2b; P<.01). Expression of alpha-actin in the intima of FK778-treated rats
      was significantly reduced when the drug was started 2 days before angioplasty in
      group 1a (P<.05) or 1 day after angioplasty in both dosage groups (group 1b,
      P<.01; group 2b, P<.05). CONCLUSION: In the double-injury rat model presented,
      balloon-mediated proliferation of smooth muscle cells in the intima with
      consecutive intimal thickening was influenced by FK778 in a dose-dependent
      manner. However, long-term studies are needed to exclude a delay of vascular
      healing in this particular model.

PMID- 16002500
TI  - Angiographic considerations in patients undergoing liver-directed therapy.
AB  - The rapid evolution and increasing complexity of liver-directed therapies has
      forced the medical community to further advance its understanding of hepatic
      arterial anatomy. The anatomy of the mesenteric system, and particularly the
      hepatic arterial bed, has been demonstrated to have a high degree of variation.
      This is important when considering presurgical planning, catheterization, and
      transarterial hepatic therapies. Although anatomic variants have been well
      described, the characterization and understanding of regional hepatic perfusion
      is also required to optimize endovascular therapy and intervention. Although this
      is true for patients undergoing bland embolization or chemoembolization, drug
      delivery, and hepatic infusional pump therapy, it is particularly true for
      intraarterial brachytherapy. The purpose of this review is to provide historical
      perspective in angiographic aspects of liver-directed therapy, as well as a
      discussion of normal vascular anatomy, commonly encountered variants, and factors
      involved in changes to regional perfusion in the presence of liver tumors.
      Methods of optimizing the safety and efficacy of liver-directed therapies with
      use of percutaneous techniques will be discussed. This review is based on the
      experience gained in treating more than 500 patients with transarterial liver
      directed therapies. Although the principles described in this article apply to
      all liver-directed therapies such as chemoembolization and administration of drug
      coated microspheres, they apply particularly to intraarterial brachytherapy.

PMID- 16002501
TI  - Yttrium 90 resin microspheres for the treatment of unresectable colorectal
      hepatic metastases after failure of multiple chemotherapy regimens: preliminary
      results.
AB  - PURPOSE: Responses to liver-directed therapy with yttrium 90 microspheres (SIR
      Spheres) and adjuvant intraarterial chemotherapy have occurred in patients with
      unresectable colorectal hepatic metastases who had received less than one
      chemotherapy regimen. Now, SIR-Spheres are being used to treat patients with
      advanced disease who have received multiple chemotherapy regimens. A
      retrospective analysis was performed to determine the technical feasibility of
      SIR-Sphere treatment in this population. MATERIALS AND METHODS: The medical
      records of 12 patients with hepatic metastatic disease and intrahepatic
      progression after multiple chemotherapy regimens for unresectable colorectal
      hepatic metastases who were treated with one or two infusions of SIR-Spheres were
      retrospectively analyzed for demographics, tumor characteristics, treatment
      details, response, and survival. RESULTS: Twelve patients underwent 17 outpatient
      infusions of SIR-Spheres. Percent hepatic tumor volume was less than 25% in four
      patients, 25%-50% in three, and more than 50% in five. Treatment in 11 patients
      with bilobar disease was accomplished via single infusions in six cases and
      sequential unilobar infusions in five patients. A single infusion was used to
      treat unilobar disease in the remaining patient. Median prescribed dose was 39.6
      mCi (mean, 37.2 mCi; range, 17-67.5 mCi); the prescribed dose exceeded the
      delivered dose in six infusions (35%) as a result of embolic arterial occlusion.
      Radiologic response was stable in five of nine patients. Carcinoembryonic antigen
      levels decreased in four of seven patients. Four patients received chemotherapy
      concomitantly or after completion of treatment. Gastric ulceration in one patient
      was managed nonoperatively. Median survival times from diagnosis and treatment
      were 24.6 and 4.5 months, respectively. CONCLUSIONS: Treatment with SIR-Spheres
      induces responses in patients with advanced unresectable colorectal hepatic
      metastases after multiple chemotherapy regimens. Inability to deliver the
      prescribed dose is related to the embolic effect of SIR-Spheres.

PMID- 16002502
TI  - Quality of life and exercise performance after aortoiliac stent placement for
      claudication.
AB  - PURPOSE: To determine the effect of aortoiliac stent placement on walking ability
      and health-related quality of life (QOL) for elderly individuals with moderate to
      severe intermittent claudication. MATERIALS AND METHODS: A prospective single
      center study was performed in 35 consecutive patients (46 symptomatic limbs) with
      intermittent claudication and aortoiliac insufficiency (mean age+/-SD, 61.1
      years+/-9.5). Baseline and follow-up data to 12 months included clinical status,
      ankle-brachial index (ABI), exercise performance according to a standardized
      treadmill exercise protocol, and self-reported health-related QOL according to
      the Walking Impairment Questionnaire (WIQ) and the Short Form 36 (SF-36).
      RESULTS: Comparing baseline with 12-month data, mean ABI significantly improved
      from 0.64+/-0.15 to 0.89+/-0.19 (P<.01). Similarly, mean initial claudication
      duration improved from 1.7 minutes+/-1.0 to 4.7 minutes+/-3.3 and maximum walking
      duration on the treadmill test improved from a mean of 3.3 minutes+/-1.8 to 8.7
      minutes+/-4.4. All WIQ subscales showed significant improvement, and the SF-36
      physical component scale as well as subscales of physical functioning, bodily
      pain, role physical, and vitality showed significant improvement. There was no 30
      day mortality. Complications in the perioperative period that required treatment
      were observed in three patients (9%), but surgery was not required for any
      complications. Importantly, urgent or emergent surgery was not required for any
      complication and no permanent disability related to complications occurred.
      CONCLUSIONS: A high technical success rate (97%) and low complication rate were
      observed. Exercise performance and health-related QOL results improved
      significantly after stent placement. Revascularization with stent placement
      should be strongly considered in addition to conservative management for moderate
      to severe claudication with aortoiliac obstruction. A randomized clinical trial
      would be needed to gauge the relative effectiveness of stent implantation and
      conservative therapy.

PMID- 16002503
TI  - Comparison of survival rates after bland arterial embolization and ablation
      versus surgical resection for treating solitary hepatocellular carcinoma up to 7
      cm.
AB  - PURPOSE: The vast majority of hepatocellular carcinomas (HCC) occur in patients
      with underlying liver dysfunction, making surgical resection available to only a
      subset of patients with adequate hepatic reserve. This study analyzes the
      authors' results with bland arterial embolization combined with radiofrequency
      ablation (RFA) or percutaneous ethanol injection (PEIT) compared with surgical
      resection for the treatment of solitary HCC up to 7 cm in size. MATERIALS AND
      METHODS: A retrospective review of all patients undergoing either surgical
      resection or bland embolization combined with local ablation for solitary HCC
      between January 1996 and August 2002 was performed. Progression-free survival
      rate and overall survival rate were calculated by the Kaplan-Meier method.
      RESULTS: There were 40 patients who underwent surgical resection and 33 patients
      who underwent embolization and ablation. Age, gender, and size of the treated
      lesion were not significantly different between the groups. The
      embolization/ablation group had more patients classified as Okuda stage II
      (P<.001). The surgical group had a longer median recurrence-free survival rate
      (53.1 vs 25.1 months). With a median follow-up of 23 months, the 1-, 3- and 5
      year actuarial overall survival rates were 97%, 77%, and 56% for the
      embolization/ablation group and 81%, 70%, and 58% for the surgical group,
      respectively. There was no statistical difference in overall survival rates
      (P=.20). CONCLUSIONS: Bland arterial embolization in combination with ablation is
      effective in treating solitary HCC lesions up to 7 cm and achieves similar
      overall survival rates to surgical resection in selected patients.

PMID- 16002504
TI  - Low-profile stent placement with the monorail technique for treatment of renal
      artery stenosis: midterm results of a prospective trial.
AB  - PURPOSE: To determine feasibility, safety, and midterm patency of a monorail
      balloon stent device for the treatment of renal artery stenosis (RAS). MATERIALS
      AND METHODS: During a period of 30 months, 47 patients (with severe hypertension,
      n=45; renal insufficiency, n=20) with 50 cases of RAS and indications for stent
      implantation (calcified ostial lesion, n=41; insufficient percutaneous
      transluminal angioplasty, n=6; dissection, n=3) were enrolled into the
      prospective evaluation. After predilation, 59 stents (Rx-Herculink 4 mm, n=2; 5
      mm, n=19; 6 mm, n=35; 7 mm, n=3) were implanted under manometer control with use
      of the long-sheath technique (5 F; 6 F for 7-mm stents) via a femoral (n=44) or
      transbrachial approach (n=6). Parameters of hypertension and renal insufficiency
      were determined before and after the procedure and for a maximum of 18 months.
      Restenosis rate was determined with color duplex ultrasonography. RESULTS: Renal
      artery stent placement (mean diameter, 5.7 mm; mean length, 16 mm) was
      technically successful in all cases (100%). Mean blood pressure and serum
      creatinine level decreased from 177/93 mm Hg to 145/78 mm Hg and from 1.8 mg/dL
      to 1.5 mg/dL, respectively. Within 48 hours after the implantation, acute
      occlusions occurred in two patients, supposedly triggered by cholesterol
      embolization. Primary and primary assisted patency rates were 87% and 92% at 6
      months and 75% and 84% at 18 months. CONCLUSIONS: Renal artery stent placement
      with the rapid-exchange monorail system is a safe procedure with promising
      patency rates. In combination with the long-sheath technique, adequate control of
      stent deployment is guaranteed during the entire intervention. The low profile of
      the device facilitates the use of small sheaths (5 F) to minimize access-site
      complications.

PMID- 16002505
TI  - Does vertebral height restoration achieved at vertebroplasty matter?
AB  - PURPOSE: Altered vertebral and spinal configuration after osteoporotic vertebral
      compression fracture (VCF) is believed to contribute to postfracture morbidity.
      The objective of this study was to determine whether patients in whom partial
      vertebral height restoration (VHR) was achieved at percutaneous vertebroplasty
      had greater pain relief or improved quality of life compared with patients in
      whom no anatomic restoration was achieved. MATERIALS AND METHODS: Consecutive
      subjects undergoing percutaneous vertebroplasty for painful osteoporotic VCFs
      completed the Osteoporosis Quality of Life Questionnaire (OQLQ) a validated,
      disease specific instrument that measures health related quality of life in women
      with osteoporosis with back pain caused by VCF. At postoperative week 2, month 2,
      and month 6, all subjects completed the mini-OQLQ, a validated extraction of
      OQLQ. Pain was rated with a standard visual analogue scale (VAS). Radiographs
      were manually digitized and evaluated for the presence of dynamic mobility and
      VHR. The relationship between VHR achieved at percutaneous vertebroplasty and
      postoperative pain relief and quality of life outcome was examined by
      multivariate analysis. RESULTS: Forty-six subjects (32 women) underwent 49
      percutaneous vertebroplasty procedures to treat 66 painful VCFs. Mean patient age
      was 74.3 years+/-10.9. Mean fracture age was 2.5 months+/-2.1. Pain rating fell
      from 7.7+/-1.8 to 2.8+/-1.8 within 1 day of percutaneous vertebroplasty and
      remained improved through month 6 (P<.001). All OQLQ domains improved
      substantially at week 2 (P<.02) and remained improved through month 6
      (P<or=.007). Preoperative dynamic mobility ranged -2.9 to 19.9 mm (average, 5.5
      mm). Postoperative VHR in mobile VCFs ranged -2.1 to 9.6 mm (average, 2.9 mm). At
      all postoperative time points up to 6 months, pain and OQLQ domain scores were
      similar in patients who achieved partial VHR at percutaneous vertebroplasty
      compared with those in whom no VHR was achieved. CONCLUSION: Partial vertebral
      height restoration achieved at percutaneous vertebroplasty did not result in
      additional pain relief or improved quality of life beyond cement fixation alone.

PMID- 16002506
TI  - Radiofrequency ablation for the treatment of liver tumors in the caudate lobe.
AB  - PURPOSE: To evaluate the effectiveness of radiofrequency (RF) ablation for liver
      tumors located in the caudate lobe. MATERIALS AND METHODS: Ten patients (46-79
      years of age; median, 70 y), eight with hepatocellular carcinoma (HCC) and
      cirrhosis and two with colorectal metastases in the caudate lobe, were treated
      with 5.8% NaCl tissue-perfused monopolar (n=7) or bipolar (n=3) RF ablation. The
      median tumor diameter was 41 mm (range, 25-70 mm). Procedures were performed
      under ultrasound and computed tomography (CT) guidance in eight and two patients,
      respectively. One month later, the treatment response was assessed by CT.
      RESULTS: Transhepatic right intercostal and transomental anterior epigastric
      routes were used for tumor puncture in eight and two patients, respectively. The
      entire RF ablation treatment required one or two procedures (median, 1.5),
      including two to 15 electrode repositionings (median, 6). After RF ablation
      procedure, one patient experienced jaundice that resolved spontaneously. In one
      patient, CT follow-up showed asymptomatic segmental biliary duct dilations.
      Median total hospital stay was 3 days (range, 2-9 d). Complete ablation was
      achieved in nine of 10 tumors. In one patient, ethanol ablation was necessary to
      complete RF ablation treatment. After a median follow up of 9.5 months (range, 5
      25 mo), three patients remained tumor-free and seven had tumor relapse: two
      local, four distant, and one mixed. Repeat RF ablation was successfully performed
      in four cases. CONCLUSION: RF ablation of liver tumors located in the caudate
      lobe is effective despite the deep location of tumors and the vicinity of major
      vessels.

PMID- 16002507
TI  - Endovascular model of rabbit hindlimb ischemia: a platform to evaluate
      therapeutic angiogenesis.
AB  - PURPOSE: Current animal hindlimb ischemia models involve surgical ligation of the
      femoral artery and delivery of therapeutic angiogenic agents into the adductor
      compartment. The authors hypothesize that an endovascular model of hindlimb
      ischemia would be a more appropriate platform, closely resembling atherosclerosis
      by occluding the vessel from within, causing less inflammation, wound healing and
      subsequent collateralization. MATERIALS AND METHODS: The left superficial femoral
      artery in 17 rabbits was occluded by endovascular coil embolization (n=9) or
      surgical ligation (n=8). Animals (n=3; in each group) were sacrificed on day 3 to
      determine the arteriolar luminal area, number of arterioles, microsphere
      determined perfusion, and degree of inflammation. On day 28, the remaining
      animals underwent calf blood pressure measurements and angiography to determine
      the number of collaterals and diameter of vessels supplying the hindlimb.
      RESULTS: Immediate postprocedure (day 0) and presacrifice (day 3 or 28) occlusion
      rates were 89% (eight of nine rabbits) and 100% for the endovascular model; 100%
      and 100% for the surgical model, respectively. Hindlimb paralysis and muscle
      atrophy was found in one surgical animal. On day 3, there was an increase in
      hindlimb perfusion (surgery, 0.04+/-0.01; endovascular, 0.02+/-0.01; P=.02), an
      increase in arteriolar luminal area (surgery, 481 microm+/-240; endovascular, 345
      microm+/-151; P=.04), and a trend toward more inflammation (surgery, 5.5+/-3.8;
      endovascular, 2.5+/-3.0; P=.08) in the surgical group. There was no difference in
      number of vessels between both groups. On day 28 there was no difference in the
      calf blood pressure ratios or in the number of collaterals. However, there was
      enlargement of the distal profunda femoris artery, the vessel closest to the
      surgical incision, in the surgical group (L/R ratio: immediate post-occlusion,
      1.06+/-0.11; day 28, 1.27+/-0.08; P=.02). CONCLUSION: The endovascular model was
      efficacious in providing occlusion of the superficial femoral artery, and induced
      less of an arteriogenic response compared with the surgical model. The authors
      believe that this endovascular model is a superior platform for studying
      therapeutic angiogenic agents.

PMID- 16002508
TI  - Pulmonary embolism: comprehensive evaluation with MR ventilation and perfusion
      scanning with hyperpolarized helium-3, arterial spin tagging, and contrast
      enhanced MRA.
AB  - PURPOSE: Development of a comprehensive magnetic resonance (MR) examination
      consisting of MR angiography (MRA) and MR ventilation and perfusion (MR V/Q) scan
      for the detection of pulmonary emboli (PE) and assessment of the technique in a
      rabbit model. MATERIALS AND METHODS: Reversible PE was induced by inflating a non
      detachable silicon balloon in the left pulmonary artery of five New Zealand White
      rabbits. MR V/Q scans were obtained prior to, during, and after balloon
      deflation. MRA was performed during balloon inflation. MR ventilation imaging was
      performed after the inhalation of hyperpolarized helium-3. MR perfusion imaging
      was performed with Flow-sensitive Alternating Inversion Recovery with an Extra
      Radiofrequency pulse technique (FAIRER). High-resolution contrast-enhanced MR
      pulmonary angiography was used to confirm the occlusion of the pulmonary artery.
      All imaging was performed on a 1.5-T whole body scanner with broadband
      capabilities. RESULTS: High-resolution ventilation images of the lungs were
      obtained. No ventilation defects were detected before, during, or after
      resolution of simulated PE. FAIRER imaging allowed visualization of pulmonary
      perfusion. No perfusion defects were detected prior to balloon inflation. During
      balloon inflation (PE), there was decreased perfusion in the left lower lobe.
      After reversal of the PE, there was improved perfusion to the left lower lobe. In
      analogy to nuclear medicine techniques, acute PE produced a mismatched defect in
      the MR V/Q scan. MRA verified the occlusive filling defect in the left pulmonary
      artery. CONCLUSION: High-resolution MRA and MR V/Q imaging of the lung is
      feasible and allows comprehensive assessment of pulmonary embolism in one imaging
      session.

PMID- 16002509
TI  - Placement of the Essure permanent birth control device with fluoroscopic
      guidance: a novel method for tubal sterilization.
AB  - An effective transcervical method for fluoroscopically guided fallopian tube
      occlusion has long been sought for female sterilization. The Essure permanent
      birth control device was approved by the Food and Drug Administration in November
      2002 and is currently indicated for hysteroscopic placement. In a series of eight
      patients, bilateral Essure microcoils were placed with fluoroscopic guidance in
      seven patients for a success rate of 87.5%. One patient described peri- and
      postprocedure pelvic pain, otherwise no complications were identified. All
      patients returned to normal activities within 24 hours. Fluoroscopically guided
      transcervical tubal sterilization with the Essure microcoil device (Conceptus,
      San Carlos, CA) is a viable outpatient procedure.

PMID- 16002510
TI  - Percutaneous retrieval of a Greenfield filter after migration to the left
      pulmonary artery.
AB  - A Titanium Greenfield filter migrated to the left pulmonary artery during its
      deployment in a 67-year-old woman. The filter was successfully removed
      percutaneously without complications with use of an Amplatz Goose Neck snare and
      the 12-F sheath from the Greenfield filter kit.

PMID- 16002511
TI  - Management of intraabdominal hypertension by percutaneous catheter drainage.
AB  - The authors report a case of an 18-year-old man with T-cell acute lymphocytic
      leukemia who developed hemorrhagic pancreatitis after chemotherapy. He
      subsequently developed abdominal compartment syndrome (ACS). Computed tomography
      showed a large fluid-filled mass in the area of the pancreas. As a result of the
      instability of his condition, surgical decompression, the standard therapy for
      ACS, was believed to carry significant morbidity and potential mortality. The
      patient underwent ultrasound-guided drainage of the peripancreatic fluid, which
      decreased his abdominal pressures and improved his clinical status. Without this
      procedure, the patient may not have tolerated subsequent surgery.

PMID- 16002512
TI  - Percutaneous treatment of a splenic artery pseudoaneurysm by thrombin injection.
AB  - Pseudoaneurysms in the visceral arteries are rare complications of pancreatitis.
      In the reported case, a 42-year-old man with a splenic pseudoaneurysm was
      successfully treated by computed tomography (CT)-guided direct thrombin injection
      into the pseudoaneurysm lumen. Selective catheterization of the splenic artery
      had proven technically impossible. During the procedure, contrast medium was
      injected via a pigtail catheter into the aorta for planning, correct positioning
      of the needle tip, and control imaging after injection. CT examinations 1 day, 3
      weeks, and 6 months after treatment demonstrated complete occlusion shrinkage of
      the pseudoaneurysm, and the patient was symptom-free.

PMID- 16002513
TI  - Transrectal radiofrequency ablation for pelvic recurrence of bladder cancer: case
      report and review of complications.
AB  - Pelvic recurrences after radical surgery for intestinal and urologic cancers can
      cause substantial pain and morbidity as a result of nerve and visceral organ
      invasion. Treatment options are frequently limited by previous radiation and
      inefficacy of systemic chemotherapy. There are a few reports of percutaneous
      radiofrequency (RF) ablation for local control or palliation of symptoms, but
      this approach has been associated with considerable morbidity. In the present
      case, transrectal RF ablation of recurrent bladder cancer was performed for
      palliation of intractable pain. The associated complications and the pertinent
      literature will be reviewed.

PMID- 16002514
TI  - Percutaneous extraction of retained biliary T-tubes: a new technique.
AB  - Retained T-tubes are rare complications after biliary surgery. The authors
      present three cases of retained T-tubes in patients with transplanted liver that
      could not be removed by a standard manual traction. The authors describe a new
      simple percutaneous method that allows removal of these T-tubes without
      complication.

PMID- 16002515
TI  - Re: the future interventional radiologist: clinician or hired gun?

PMID- 16002517
TI  - Retrieval of Bard recovery filter from left-sided inferior vena cava.

PMID- 16002519
TI  - Type III endoleak caused by fabric tear of a Zenith endograft after low-pressure
      balloon modeling.

PMID- 16002518
TI  - Duodenal perforation caused by an indwelling catheter during hepatic arterial
      infusion chemotherapy.

PMID- 16002522
TI  - Enhanced sexual behaviors and androgen receptor immunoreactivity in the male
      progesterone receptor knockout mouse.
AB  - Reproductive and behavioral functions of progesterone receptors (PRs) in males
      were assessed by examining consequences of PR gene deletion. Basal hormone levels
      were measured in male progesterone receptor knockout (PRKO) mice and compared to
      wild-type (WT) counterparts. RIA of serum LH, testosterone, and progesterone
      levels revealed no significant differences. Levels of FSH were moderately but
      significantly lower and inhibin levels were higher in PRKOs; these differences
      were not accompanied by gross differences in testicular weight or morphology.
      PRKOs exhibited significant alterations in sexual behavior. In initial tests
      PRKOs exhibited reduced latency to mount, compared with WT. In second sessions,
      PRKOs again showed a significantly reduced latency to mount and increased
      likelihood of achieving ejaculation. RU486 treatment in WT produced increased
      mount and intromission frequency and decreased latency to intromission. In
      anxiety-related behavior tests, PRKO mice exhibited intermediate anxiety levels,
      compared with WT, suggesting that enhanced sexual behavior in PRKOs is not
      secondary to reduced anxiety. Immunohistochemical analysis revealed significantly
      enhanced androgen receptor expression in the medial preoptic nucleus and bed
      nucleus of the stria terminalis of PRKO. We conclude that testicular development
      and function and homeostatic regulation of the hypothalamic-pituitary testicular
      axis are altered to a lesser extent by PR gene deletion. In contrast, PR appears
      to play a substantial role in inhibiting the anticipatory/motivational components
      of male sexual behavior in the mouse. The biological significance of this
      inhibitory mechanism and the extent to which it is mediated by reduced androgen
      receptor expression remain to be clarified.

PMID- 16002523
TI  - Tungstate decreases weight gain and adiposity in obese rats through increased
      thermogenesis and lipid oxidation.
AB  - The increasing worldwide incidence of obesity and the limitations of current
      treatments raise the need for finding novel therapeutic approaches to treat this
      disease. The purpose of the current study was first to investigate the effects of
      tungstate on body weight and insulin sensitivity in a rat model of diet-induced
      obesity. Second, we aimed to gain insight into the molecular mechanisms
      underlying its action. Oral administration of tungstate significantly decreased
      body weight gain and adiposity without modifying caloric intake, intestinal fat
      absorption, or growth rate in obese rats. Moreover, the treatment ameliorated
      dislipemia and insulin resistance of obese rats. These effects were mediated by
      an increase in whole-body energy dissipation and by changes in the expression of
      genes involved in the oxidation of fatty acids and mitochondrial uncoupling in
      adipose tissue. Furthermore, treatment increased the number of small adipocytes
      with a concomitant induction of apoptosis. Our results indicate that tungstate
      treatment may provide the basis for a promising novel therapy for obesity.

PMID- 16002520
TI  - Hormonal and metabolic defects in a prader-willi syndrome mouse model with
      neonatal failure to thrive.
AB  - Prader-Willi syndrome (PWS) has a biphasic clinical phenotype with failure to
      thrive in the neonatal period followed by hyperphagia and severe obesity
      commencing in childhood among other endocrinological and neurobehavioral
      abnormalities. The syndrome results from loss of function of several clustered,
      paternally expressed genes in chromosome 15q11-q13. PWS is assumed to result from
      a hypothalamic defect, but the pathophysiological basis of the disorder is
      unknown. We hypothesize that a fetal developmental abnormality in PWS leads to
      the neonatal phenotype, whereas the adult phenotype results from a failure in
      compensatory mechanisms. To address this hypothesis and better characterize the
      neonatal failure to thrive phenotype during postnatal life, we studied a
      transgenic deletion PWS (TgPWS) mouse model that shares similarities with the
      first stage of the human syndrome. TgPWS mice have fetal and neonatal growth
      retardation associated with profoundly reduced insulin and glucagon levels.
      Consistent with growth retardation, TgPWS mice have deregulated liver expression
      of IGF system components, as revealed by quantitative gene expression studies.
      Lethality in TgPWS mice appears to result from severe hypoglycemia after
      postnatal d 2 after depletion of liver glycogen stores. Consistent with
      hypoglycemia, TgPWS mice appear to have increased fat oxidation. Ghrelin levels
      increase in TgPWS reciprocally with the falling glucose levels, suggesting that
      the rise in ghrelin reported in PWS patients may be secondary to a perceived
      energy deficiency. Together, the data reveal defects in endocrine pancreatic
      function as well as glucose and hepatic energy metabolism that may underlie the
      neonatal phenotype of PWS.

PMID- 16002521
TI  - Deoxyribonucleic acid microarray analysis of gene expression pattern in the
      arcuate nucleus/ventromedial nucleus of hypothalamus during lactation.
AB  - Lactation is characterized by extreme hyperphagia and negative energy balance
      resulting from a large energy drain due to milk production and by a suppression
      of cyclic ovarian function. Increases in neuropeptide Y and agouti-related
      protein and a decrease in proopiomelanocortin expression in the arcuate nucleus
      of hypothalamus (ARH) may contribute to the hyperphagia to maintain energy
      balance and to the suppression of LH secretion associated with lactation.
      However, little is known about the full extent of neuroendocrine changes in the
      ARH that may contribute to the various adaptations occurring during lactation. To
      address this issue, we used Affymetrix microarray to acquire a reliable profile
      of the lactation-induced transcriptional changes in micropunches containing the
      ARH and a portion of the ventromedial nucleus of the hypothalamus. Using high
      stringency criteria, 12 genes were identified as being differentially regulated
      during lactation, and an additional 10 genes and three transcribed sequences were
      identified using moderate stringency criteria. Changes in neuropeptide Y,
      enkephalin, tyrosine hydroxylase, and dynorphin, genes previously shown to be
      differentially regulated during lactation, provide validation for the microarray
      analysis. New genes identified as being differentially expressed include those
      related to neurotransmission, growth factors, signal transduction, and structure
      remodeling. These data identify new genes in ARH/ventromedial nucleus of the
      hypothalamus that may play an important role in the adaptations of lactation
      related to hyperphagia, milk production, and the suppression of cyclic
      reproductive function and may contribute to elucidating a framework for
      integrating changes in energy intake with the regulation of reproductive function
      during lactation.

PMID- 16002524
TI  - Cyclic adenosine 3',5'-monophosphate-dependent activation of mitogen-activated
      protein kinase in cumulus cells is essential for germinal vesicle breakdown of
      porcine cumulus-enclosed oocytes.
AB  - MAPK plays an important role during meiotic maturation in mammalian oocytes,
      whereas the necessity of MAPK during meiotic resumption in porcine oocytes is
      still controversial. Here, by applying the method of ultracentrifugation to move
      the opaque lipid droplets to the edge of the oocyte, therefore allowing clear
      visualization of porcine germinal vesicles, oocytes just before germinal vesicle
      breakdown (GVBD) and those that had just undergone GVBD were selected for the
      assay of MAPK activation. Our results showed that phosphorylation of MAPK in
      oocytes occurred after GVBD in all three different culture models: spontaneous
      maturation model, inhibition-induction maturation model, and normal maturation
      model. Moreover, we found that activation of MAPK in cumulus cells but not in
      oocytes was essential for GVBD in cumulus-enclosed oocytes. Then the cross-talk
      between cAMP and MAPK in cumulus cells was investigated by using cell-type
      specific phosphodiesterase (PDE) isoenzyme inhibitors. Our results showed that
      PDE3 subtype existed in oocytes, whereas PDE4 subtype existed in cumulus cells.
      PDE3 inhibitor prevented meiotic resumption of oocytes, whereas PDE4 inhibitor
      enhanced the ability of FSH or forskolin to activate MAPK in cumulus cells. We
      propose that increased cAMP resulting from inhibition of PDE3 in oocytes blocks
      GVBD, whereas increased cAMP resulting from inhibition of PDE4 activates MAPK
      pathway in cumulus cells, which is essential for GVBD induction.

PMID- 16002526
TI  - Insulin response sequence-dependent and -independent mechanisms mediate effects
      of insulin on glucocorticoid-stimulated insulin-like growth factor binding
      protein-1 promoter activity.
AB  - IGF binding protein-1 (IGFBP-1) gene expression is stimulated by glucocorticoids
      and suppressed by insulin in the liver. Insulin response sequences (IRSs) mediate
      effects of insulin on basal promoter function, whereas glucocorticoids stimulate
      promoter activity through a contiguous glucocorticoid response element. Here we
      examined the role of IRS-dependent and -independent mechanisms in mediating
      insulin and glucocorticoids effects on IGFBP-1 promoter activity. Dexamethasone
      (Dex) stimulates IGFBP-1 promoter activity in HepG2 cells, and mutation of IRSs
      reduces this effect, indicating that IRS-associated factors enhance
      glucocorticoid effects on promoter function. Conversely, insulin inhibits basal
      promoter activity by 40% and Dex-stimulated promoter activity by 65%, indicating
      that glucocorticoids enhance the ability of insulin to suppress promoter
      activity. Mutation of IRSs completely disrupts the insulin effect on basal
      promoter activity and reduces but does not abolish inhibition of Dex-stimulated
      promoter activity, indicating that insulin suppresses glucocorticoid-stimulated
      promoter activity through both IRS-dependent and -independent mechanisms. IRS
      independent effects of insulin are context dependent because insulin does not
      suppress glucocorticoid-stimulated activity of a promoter containing multiple
      glucocorticoid response elements. Cotransfection studies indicate that
      suppression of peroxisomal proliferator-activated receptor-gamma coactivator
      1alpha, an insulin-regulated coactivator of the glucocorticoid receptor, is not
      required for this effect of insulin. Studies with pharmacological inhibitors
      indicate that both phosphatidylinositol-3' kinase and mitogen-activated kinase
      kinase pathways contribute to IRS-independent effects. These studies indicate
      that glucocorticoids and IRS-associated factors function together to mediate
      effects of insulin and glucocorticoids on promoter activity and that
      glucocorticoid treatment creates a complex environment in which insulin regulates
      IGFBP-1 expression through both IRS-dependent and IRS-independent mechanisms.

PMID- 16002525
TI  - Cyclooxygenase-2 regulation of the age-related decline in testosterone
      biosynthesis.
AB  - The age-related decline in testosterone biosynthesis in testicular Leydig cells
      has been well documented, but the mechanisms involved in the decline are not
      clear. Recent studies have described a cyclooxygenase-2 (COX2)-dependent tonic
      inhibition of Leydig cell steroidogenesis and expression of the steroidogenic
      acute regulatory protein (StAR). The present study was conducted to determine
      whether COX2 protein increases with age in rat Leydig cells and whether COX2
      plays a role in the age-related decline in testosterone biosynthesis. Our results
      indicate that from 3 months of age to 30 months, COX2 protein in aged rat Leydig
      cells increased by 346% over that of young Leydig cells, StAR protein decreased
      to 33%, and blood testosterone concentration and testosterone biosynthesis in
      Leydig cells decreased to 41 and 33%, respectively. Further experiments
      demonstrated that overexpressing COX2 in MA-10 mouse Leydig cells inhibited StAR
      gene expression and steroidogenesis and that the inhibitory effects of COX2 could
      be reversed by blocking COX2 activity. Notably, incubation of aged Leydig cells
      with the COX2 inhibitor NS398 enhanced their testosterone biosynthesis. Blood
      testosterone concentrations in aged rats fed the COX2 inhibitor DFU, at doses of
      5, 10, 15, and 20 mg/kg body weight per day were increased by 15, 23, 56, and
      120%, respectively, over the levels in the rats receiving no DFU. The present
      study suggests a novel mechanism in male aging involving COX2 and a potential
      application of the mechanism to delay the age-related decline in testosterone
      biosynthesis.

PMID- 16002527
TI  - AKT activation promotes metastasis in a mouse model of follicular thyroid
      carcinoma.
AB  - The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions,
      and its dysregulation in tumors is a common finding. The molecular basis of
      follicular thyroid cancer metastasis is not well understood but may also be
      influenced by AKT activation. We previously created a knockin mutant mouse that
      expresses a mutant thyroid hormone receptor-beta gene (TRbetaPV mouse) that
      spontaneously develops thyroid cancer and distant metastasis similar to human
      follicular thyroid cancer. In this study, we investigated whether our mouse model
      exhibits similar AKT activation as human follicular thyroid cancer. Western blot
      analysis on thyroids from both wild-type and TRbeta(PV/PV) mice revealed
      elevation of activated AKT in TRbeta(PV/PV) mice. Immunohistochemistry and
      confocal microscopy reveal activated AKT in both the thyroid and metastatic
      lesions of TRbeta(PV/PV) mice. Whereas all three AKT isoforms were overexpressed
      in primary tumors from TRbeta(PV/PV) mice in the cytoplasm of thyroid cancer
      cells, only AKT1 was also found in the nucleus, matching the localization of
      activated AKT in a pattern similar to human follicular thyroid cancer. In the
      metastases, all AKT isoforms correlated with phosphorylated AKT nuclear
      localization. We created primary thyroid cell lines derived from TRbeta(PV/PV)
      mice and found reduction of phosphorylated AKT levels or AKT downstream targets
      diminishes cell motility. Activated AKT is common to both human and mouse
      follicular thyroid cancer and is correlated with increased cell motility in vitro
      and metastasis in vivo. Thus, TRbeta(PV/PV) mice could be used to further dissect
      the detailed pathways underlying the progression and metastasis of follicular
      thyroid carcinoma.

PMID- 16002528
TI  - A new selective estrogen receptor modulator with potent uterine antagonist
      activity, agonist activity in bone, and minimal ovarian stimulation.
AB  - The use of selective estrogen receptor modulators for the treatment of estrogen
      dependent diseases in premenopausal women has been hindered by undesirable
      ovarian stimulation and associated risks of ovarian cysts. We have identified a
      selective estrogen receptor modulator compound (LY2066948) that is a strong
      estrogen antagonist in the uterus yet has minimal effects on the ovaries of rats.
      LY2066948 binds with high affinity to both estrogen receptors and has potent
      estrogen antagonist activity in human uterine and breast cancer cells. Oral
      administration of LY2066948 to immature rats blocked uterine weight gain induced
      by ethynyl estradiol with an ED50 of 0.07 mg/kg. Studies in mature rats
      demonstrated that LY2066948 decreases uterine weight by 51% after 35 d treatment,
      confirming potent uterine antagonist activity over several estrous cycles. This
      strong uterine response contrasted with the minimal effects on the ovaries: serum
      estradiol levels remained within the normal range, whereas histologic evaluation
      showed granulosa cell hyperplasia in few of the rats. Bone studies demonstrated
      that LY2066948 prevented ovariectomy-induced bone loss and treatment of ovary
      intact rats caused no bone loss, confirming estrogen receptor agonist skeletal
      effects. Collectively, these data show that LY2066948 exhibits a tissue-specific
      profile consistent with strong antagonist activity in the uterus, agonist
      activity in bone, and minimal effects in the ovaries.

PMID- 16002529
TI  - Consumption of a fat-rich diet activates a proinflammatory response and induces
      insulin resistance in the hypothalamus.
AB  - Obesity has reached epidemic proportions in several regions of the world. General
      changes in lifestyle, including consumption of fat-rich food, are among the most
      important factors leading to an unprecedented increase in the prevalence of this
      disease. Weight gain results from an imbalance between caloric intake and energy
      expenditure. Both of these parameters are under the tight control of specialized
      neurons of the hypothalamus that respond to peripheral anorexigenic and
      adipostatic signals carried by leptin and insulin. Here we show, by macroarray
      analysis, that high-fat feeding [hyperlipidic diet (HL)] induces the expression
      of several proinflammatory cytokines and inflammatory responsive proteins in
      hypothalamus. This phenomenon is accompanied by increased activation of c-Jun N
      terminal kinase and nuclear factor-kappaB. In addition, HL feeding leads to
      impaired functional and molecular activation of the insulin-signaling pathway,
      which is paralleled by increased serine phosphorylation of the insulin receptor
      and insulin receptor substrate-2. Intracerebroventricular treatment of HL rats
      with a specific inhibitor of c-Jun N-terminal kinase (SP600125) restores insulin
      signaling and leads to a reduced caloric intake and weight loss. We conclude that
      HL feeding induces a local proinflammatory status in the hypothalamus, which
      results in impaired anorexigenic insulin signaling.

PMID- 16002530
TI  - Reduced ghrelin, islet amyloid polypeptide, and peptide YY expression in the
      stomach of gastrin-cholecystokinin knockout mice.
AB  - The antral hormone gastrin and its intestinal relative, cholecystokinin (CCK),
      are pivotal in the regulation of gastric functions. Other gastric hormones like
      ghrelin, peptide YY (PYY), and islet amyloid polypeptide (IAPP), however, also
      contribute to the regulation of acid secretion, motility, and feeding. Because
      gastrin and CCK are crucial for gastric homeostasis, we examined how loss of
      gastrin alone and gastrin plus CCK affected the expression of ghrelin, IAPP, and
      PYY and ghrelin secretion. The expression of ghrelin, IAPP, and PYY and the CCK-A
      receptor genes were examined in both gastrin and gastrin-CCK double-knockout (KO)
      mice using immunocytochemistry and quantitative RT-PCR. Ghrelin concentrations in
      plasma were measured using RIA. Gastrin and CCK were infused in gastrin-CCK KO
      mice using osmotic minipumps. The number of ghrelin cells and ghrelin gene
      expression were unaffected, albeit the ghrelin cells were located closer to the
      base of the glands in both KO mouse strains when freely fed. However, lack of
      both gastrin and CCK attenuated fasting-induced ghrelin expression and secretion.
      Fundic ghrelin cells expressed the CCK-A receptor, and ghrelin expression
      increased after CCK infusion. Furthermore, gastric IAPP and PYY expression as
      well as the number of IAPP- and PYY-containing cells were reduced in both gastrin
      and gastrin-CCK KO mice. Gastrin infusion increased gastric IAPP but not PYY
      expression. In conclusion, lack of gastrin plus CCK but not gastrin alone reduced
      ghrelin secretion in response to fasting through both direct and indirect
      mechanisms. Both gastrin and combined gastrin-CCK deficiency reduced the gastric
      IAPP and PYY expression.

PMID- 16002531
TI  - The new biology of aldosterone.
AB  - Classically, aldosterone is synthesised in the adrenal zona glomerulosa and binds
      to specific mineralocorticoid receptors located in the cytosol of target
      epithelial cells. Translocation of the resulting steroid receptor complex to the
      cell nucleus modulates gene expression and translation of specific 'aldosterone
      induced' proteins that regulate electrolyte and fluid balance. However, non
      epithelial and rapid non-genomic actions of aldosterone have also been described
      that account for a variety of actions of aldosterone that contribute to blood
      pressure homeostasis. These include key actions on endothelial cells and on
      cardiac tissue. There is also evidence that aldosterone can be synthesised in
      other tissues; the most convincing evidence relates to the central nervous
      system. However, suggestions that aldosterone is produced in the heart remain
      controversial, and adrenal derived aldosterone is the principal source of
      circulating and locally available hormone. Recent studies have shown major
      therapeutic benefits of mineralocorticoid receptor antagonism in cardiac failure,
      which emphasise the importance of aldosterone in causing adverse cardiovascular
      pathophysiological effects. Additional evidence demonstrates that aldosterone
      levels predict development of high blood pressure in normotensive subjects, while
      it is now clear that increased aldosterone action contributes to hypertension and
      cardiovascular damage in approximately 10% of patients with established
      hypertension. These new findings highlight the role of aldosterone as a key
      cardiovascular hormone and extend our understanding of its role in determining
      adverse cardiovascular outcomes.

PMID- 16002532
TI  - Androgen regulation of satellite cell function.
AB  - Androgen treatment can enhance the size and strength of muscle. However, the
      mechanisms of androgen action in skeletal muscle are poorly understood. This
      review discusses potential mechanisms by which androgens regulate satellite cell
      activation and function. Studies have demonstrated that androgen administration
      increases satellite cell numbers in animals and humans in a dose-dependent
      manner. Moreover, androgens increase androgen receptor levels in satellite cells.
      In vitro, the results are contradictory as to whether androgens regulate
      satellite cell proliferation or differentiation. IGF-I is one major target of
      androgen action in satellite cells. In addition, the possibility of non-genomic
      actions of androgens on satellite cells is discussed. In summary, this review
      focuses on exploring potential mechanisms through which androgens regulate
      satellite cells, by analyzing developments from research in this area.

PMID- 16002533
TI  - Coregulatory protein-orphan nuclear receptor interactions in the human adrenal
      cortex.
AB  - The capacity of the adrenal to produce steroids is controlled in part through the
      transcriptional regulation of steroid enzymes. The orphan nuclear receptor
      steroidogenic factor 1 (SF-1) is central to the transcriptional regulation of all
      steroid hydroxylase enzymes, whereas nur77 can preferentially regulate steroid
      enzyme genes relevant to cortisol production. We hypothesised that, in the
      presence of secretagogues, SF-1 and nur77 may differentially interact with
      coregulatory proteins in the human adrenal cortex. Both coregulatory proteins,
      steroid receptor coactivator (SRC-1) and silencing mediator for retinoid and
      thyroid hormones (SMRT), were found to be expressed in the zona fasciculata and
      reticularis in the human adrenal cortex, but were largely absent from the zona
      glomerulosa. Both coregulatory proteins were colocalised with SF-1 and nur77. In
      the H295R adrenal tumour cell line, SF-1 and nur77 transcripts were increased in
      cells in the presence of forskolin, whereas nur77 mRNA was also induced with
      angiotensin II (AII). The coactivator SRC-1 mRNA was increased in the presence of
      both forskolin and AII. Forskolin induced recruitment of SRC-1 to the SF-1
      response element and induced SRC-1-SF-1 interactions, whereas AII increased
      recruitment of SRC-1 to the nur77 response element and induced SRC-1-nur77
      interactions. The corepressor SMRT interacted with SF-1 in the presence of AII
      and with nur77 in cells treated with forskolin. Orphan nuclear receptor
      coregulatory protein interactions may have consequences for the regulation of key
      steroidogenic enzymes in the human adrenal cortex.

PMID- 16002534
TI  - A paradoxical inhibitory effect of oestradiol-17beta on GnRH self-priming in
      pituitaries from tamoxifen-treated rats.
AB  - Two-week ovariectomized (OVX) rats were injected over three days with 25 microg
      oestradiol benzoate (EB), 3 mg tamoxifen (TX) and 0.2 ml oil and their
      pituitaries were harvested for incubation experiments. Pituitaries from EB- and
      TX-treated OVX rats exhibited GnRH self-priming when incubated with their
      corresponding ligand. However, incubation of pituitaries with different ligands
      yielded divergent results: when pituitaries from EB-treated rats were incubated
      with 10(-7) M TX they displayed GnRH self-priming, whereas incubation of
      pituitaries from TX-treated rats with 10(-8) M oestradiol-17beta (E2) blocked
      GnRH self-priming. Further studies to analyse the latter finding revealed that:
      (a) E2 inhibited TX-induced GnRH self-priming in a dose-dependent manner while
      10(-8) M oestradiol-17alpha did not; (b) co-incubation of E2 with the pure anti
      oestrogen ICI 182,780, but not with the selective oestrogen receptor modulator
      TX, reversed the E2 inhibitory effect; (c) the oestrogen receptor (ER)-alpha
      selective agonist propylpyrazole triol, but not the ERbeta selective agonist
      diarylpropionitrile, mimicked the inhibitory effect of E2; (d) the analogue
      membrane-impermeable conjugated E2-BSA also inhibited TX-induced GnRH self
      priming; and (e) a 15-min exposure of the pituitaries to E2 was sufficient to
      inhibit the GnRH self-priming elicited by TX. Although other explanations may
      exist, altogether these results suggested that E2, via an ER different from
      classical ER, inhibits the GnRH self-priming elicited by TX.

PMID- 16002535
TI  - The estrogen receptor alpha sigma3 mRNA splicing variant is differentially
      regulated by estrogen and progesterone in the rat uterus.
AB  - The gene for estrogen receptor alpha (ER alpha) has been shown to be under
      complex hormonal control and its activity can be regulated by mRNA alternative
      splicing. Here we examined the regulation of ER alpha transcription and
      translation in the rat uterus by ovarian steroid hormones. We examined whether
      expression of ER alpha mRNA splice isoforms is hormonally regulated in
      ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily
      with 17-beta estradiol (E2) (0.05 microg/rat or 5 microg/rat), progesterone (P4)
      (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h
      after the last injection and uterine horns were removed. In order to determine
      whether ER alpha mRNA isoforms are differentially expressed under various
      physiological conditions, animals were evaluated at proestrus, estrus and
      diestrus. The ER alpha protein and mRNA were detected by immunohistochemistry and
      comparative RT-PCR analysis respectively. The presence of ER alpha mRNA isoforms
      was evaluated using a nested RT-PCR assay. In OVX control rats, ER alpha mRNA and
      protein levels were high, demonstrating a constitutive expression of the ER alpha
      gene in the uterus. When animals received P4 or the high dose of E2, a
      significant decrease in both ER alpha mRNA and protein was observed in the
      uterus. However, when rats were protein was treated with the low dose of E2, only
      the ER alpha down-regulated; no changes were observed in ER alpha mRNA
      expression. In addition to the full-length ER alpha mRNA, OVX control rat uteri
      expressed three shorter transcripts: sigma3, sigma4 and sigma3,4 (lacking exon 3,
      exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were
      treated with P4, the low dose of E2 or a combination of both steroids, expression
      of the sigma3 isoform was completely abolished. During the estrous cycle, all ER
      alpha mRNA splicing variants were detected at proestrus and estrus. However, in
      diestrus, significant low levels of the sigma3 isoform were observed. In summary,
      our results suggest a dose-dependent relationship between E2 concentrations and
      the level of control in the ER alpha transcription-translation cascade. Moreover,
      the alternative splicing of the ER alpha primary transcript is influenced by the
      hormonal milieu, suggesting that these events could affect the estrogen
      responsiveness of the rat uterus during the estrous cycle.

PMID- 16002537
TI  - Microvascular effects of corticotropin-releasing hormone in human skin vary in
      relation to estrogen concentration during the menstrual cycle.
AB  - Females have a significantly greater life expectancy than males, which in part
      may be due to the cardio-protective effects of the female sex hormone, estrogen,
      on vascular function. However, the sex-specific mechanisms contributing to these
      differences are complex and not fully understood. Previously we have reported
      that corticotropin-releasing hormone (CRH) has potent dilator effects in the
      female skin circulation via mast cell degranulation. Furthermore the dilator
      response to CRH was more enhanced in females than in age-matched males,
      suggesting that estrogens may be involved. In this study we examined whether CRH
      induced dilation and endothelial cell-dependent dilation in the skin circulation
      of pre-menopausal females were associated with changes in estrogen during the
      menstrual cycle. CRH-induced dilation (1 nM) was enhanced in the presence of high
      circulating concentrations of estrogen and a positive correlation was identified
      between CRH-induced dilation and plasma estrogen concentrations. Endothelial cell
      dependent dilation was examined using acetylcholine. Acetylcholine-induced
      dilation (1 nM) was not correlated with circulating concentrations of estrogen.
      These data suggest the variation in CRH-induced dilation in the skin
      microvasculature during the menstrual cycle may be due to estrogenic effects on
      mast cell function and not due to direct changes in endothelial cell function.

PMID- 16002536
TI  - Influence of exogenous oestrogen or (anti-) androgen administration on soluble
      transferrin receptor in human plasma.
AB  - The objective of this investigation was to study the effects of sex steroids on
      levels of haemoglobin (Hb) and haematocrit (Hct) and to analyse whether these
      effects can be related to levels of the soluble transferrin receptor (sTfR), a
      marker of erythropoietic activity. Nineteen male-to-female transsexuals were
      randomly assigned to either oral ethinyl oestradiol (EE) (n=12) or transdermal
      17beta-oestradiol (E2) (n=7); both treatments included the anti-androgen
      cyproterone acetate (CA). Six male-to-female transsexuals were treated with CA
      only. Fifteen female-to-male transsexuals were treated with i.m. testosterone
      esters. The Hct, and levels of Hb, IGF-I, GH and sTfR were measured before and
      after 4 months of hormone administration. Androgen administration significantly
      increased the sTfR concentration by 31.5% (P=0.008) and increased levels of Hct,
      Hb and IGF-I. Both regimens of CA with oral EE and transdermal E2 reduced plasma
      testosterone similarly to castrate values and decreased Hb and Hct. The CA+oral
      EE combination induced a decrease in sTfR of 19.0% (P=0.002) which was not the
      case with CA+transdermal E2 (P=0.27). This cannot be explained by the profound
      decline in plasma testosterone which was similar with both regimens, but this
      difference could be related to the different effects of the two regimens on
      plasma IGF-I. This assumption is supported by the positive correlation that was
      found to exist between plasma sTfR and IGF-I after the interventions (P<0.05).

PMID- 16002539
TI  - Activation of the p38 MAPK pathway by follicle-stimulating hormone regulates
      steroidogenesis in granulosa cells differentially.
AB  - In the present study, we started out to test whether the follicle-stimulating
      hormone (FSH)-activated p38 MAPK signaling cascade was involved in the regulation
      of steroidogenesis in granulosa cells (GCs). GCs were prepared from the ovaries
      of DES-treated immature rats and cultured in serum-free medium. Treatment of GCs
      with FSH (50 ng/ml) induced the phosphorylation of p38 MAPK rapidly with the
      phosphorylation being observed within 5 min and reaching the highest level at 30
      min. Such activation was protein kinase A-dependent as indicated by the results
      using specific inhibitors. FSH stimulated the production of progesterone and
      estradiol as well as the expression of the steroidogenic acute regulatory protein
      (StAR) in a time-dependent manner, with a maximum level being observed in the
      production of progesterone and StAR at 48 h. Moreover, the potent p38 MAPK
      inhibitor SB203580 (20 microM) augmented FSH-induced progesterone and StAR
      production, while reduced FSH-induced estradiol production at the same time
      (P<0.01). RT-PCR data showed that inclusion of SB203580 in the media enhanced FSH
      stimulated StAR mRNA production, while decreased the FSH-stimulated P450arom mRNA
      expression (P<0.05). Immunocytochemical studies showed that FSH treatment
      together with the inhibition of p38 MAPK activity resulted in a higher expression
      of StAR in mitochondria than FSH treatment alone. FSH also significantly up
      regulated the protein level of LRH-1, a member of the orphan receptor family that
      activates the expression of P450arom in ovaries and testes. p38 MAPK inactivation
      down-regulated the basal and FSH-induced LRH-1 expression significantly. The
      intra-cellular level of DAX-1, another orphan receptor that inhibits StAR
      expression, also decreased upon p38 MAPK being inactivated. For the first time,
      the present study suggests that FSH-activated p38 MAPK signal pathway regulates
      progesterone and estrogen production in GCs differentially, and that the
      transcription factors LRH-1 and DAX-1 might play important roles in the process.

PMID- 16002538
TI  - Characteristics of salivary profiles of oestradiol and progesterone in
      premenopausal women.
AB  - The objective of the study was to characterize salivary sex steroid levels in 56
      women undergoing annual mammography who were participating in a breast density
      study at the Lynn Sage Breast Center of Northwestern Memorial Hospital, and to
      determine the predictability of the patterns within women. Saliva was collected
      daily by the women at home for one complete menstrual cycle and then again at
      approximately 6-month intervals. The occurrence of sporadic anovulatory cycles
      was identified in 12 subjects, and persistent oestradiol (OE2) elevation in all
      three cycles without significant progesterone levels occurred in another five
      subjects. In addition, both OE2 and progesterone were significantly lower in
      initial menstrual cycles than in subsequent cycles, suggestive of an effect of
      participation in the study on hormone levels. Initial salivary OE2 levels were
      not good predictors of corresponding levels in either follicular or luteal phases
      of the menstrual cycles at the 6-month intervals. However, after the initial
      cycle, progesterone levels were highly predictable within individuals over a
      period of 6 months (r=0.78, P<0.001). The study emphasizes the natural variation
      among and within women in the absence of any intervention, and indicates the need
      for properly controlled studies before attributing changes in hormonal levels to
      therapy. In addition, it emphasizes the importance of sampling at multiple time
      points when examining the relationship between hormones and risk.

PMID- 16002540
TI  - Differential expression and seasonal modulation of VGF peptides in sheep
      pituitary.
AB  - The inducible gene vgf and its peptide products are relevant to the
      neuroendocrine regulation of homeostasis and reproduction in rodents. We show
      here that in the anterior pituitary of female sheep the somatotrope, gonadotrope,
      and lactotrope/thyrotrope cell populations each expressed vgf mRNA, but displayed
      a distinct profile of VGF immunoreactive peptides. ProVGF C-terminus and VGF(443
      588) immunoreactivities were found in lactotropes and thyrotropes, often in a
      subcellular location restricted to the Golgi area and suggestive of rapid peptide
      (or proVGF) release upon biosynthesis, while high molecular weight bands
      consistent with proVGF were shown in pituitary extracts. Distinct seasonal
      changes were revealed, proVGF C-terminus immunoreactive cells being largely
      identified as lactotropes during the summer (83.7 +/- 2.1% (mean +/-s.e.m.)
      versus 27.0 +/- 1.9% during the winter), as opposed to thyrotropes during the
      winter (73.0 +/- 1.9% versus 16.3 +/- 2.1% during the summer). Conversely,
      antisera to peptides adjacent to the 'Arg-Pro-Arg' cleavage site, and to the
      VGF(553-555) N-terminus of the proVGF-derived peptide V, selectively labeled
      gonadotropes, indicating processing to small peptides not retaining the proVGF C
      terminus in such cells. Finally, a peptide related to the VGF(4-240) region was
      immunostained in somatotropes, shown in a Western blot as a band of relative
      molecular mass of approximately 16,000. In conclusion, a complex, endocrine cell
      type-specific processing of proVGF was revealed. Further to the known
      inducibility of vgf mRNA upon a range of stimuli, discreet, selective modulations
      of VGF-peptide profile/s are suggested, possibly involved in specific
      neuro/endocrine or modulatory mechanisms.

PMID- 16002543
TI  - Quantification of stem cell factor mRNA levels in the rat testis: usefulness of
      clusterin mRNA as a marker of the amount of mRNA of Sertoli cell origin in post
      pubertal rats.
AB  - Spermatogenesis is a complex cellular process regulated by gonadotrophins and
      local cell-cell interactions. Stem cell factor (SCF) is one of the paracrine
      factors, produced by the Sertoli cells, involved in the local regulation of
      spermatogenesis. Measurement of its testicular level is important for addressing
      its role in testis physiopathology. However, the relative cell composition of
      experimental and pathological testis samples may lead to misinterpretation in
      relating SCF mRNA levels to the amount of RNA extracted from the whole tissue
      sample. Taking into account the relative RNA content of Sertoli cell origin
      should provide more significant data. In the present study, three sets of
      experiments were intended for modifying the proportion of RNA of Sertoli cell
      origin in RNA extracted from whole testis tissue samples: during postnatal
      development; following methoxy-acetic acid (MAA) administration; and after
      injecting a long-acting gonadotrophin-releasing hormone agonist (GnRHa). In a
      first step, we demonstrated clusterin mRNA level stability in purified Sertoli
      cell preparations between 20 days and adulthood, and following MAA or GnRHa
      treatment. In a second step, we used a competitive RT-PCR assay to measure SCF
      and clusterin mRNA levels and expressed the amount of SCF mRNA relative to the
      amount of clusterin mRNA under the above experimental conditions. The
      SCF/clusterin mRNA level ratio was found to remain roughly stable from 20 days
      post-partum to adulthood; i.e. during the development of spermatogenesis. MAA
      administration led to an overall increase in the SCF/clusterin mRNA level ratio
      between 7 and 14 days after administration, consistent with the replenishment of
      the testis with pachytene spermatocytes and round spermatids. Conversely, after
      long-acting GnRHa injection, the SCF/clusterin mRNA level ratio decreased only
      slightly from day 21 onward. Hence, the present studies indicate that, under
      physiopathological conditions, the amount of clusterin mRNA is a good marker of
      the amount of RNA of Sertoli cell origin in testis samples at day 20 or later;
      different experimental alterations of spermatogenesis are associated with
      different patterns of SCF mRNA levels; the relationship between FSH and SCF in
      vivo is not as simple as that described in vitro.

PMID- 16002542
TI  - Stress elevates corticotropin-releasing factor (CRF) and CRF-binding protein mRNA
      levels in rainbow trout (Oncorhynchus mykiss).
AB  - The objectives of this study were to characterize rainbow trout (Oncorhynchus
      mykiss) corticotropin-releasing factor (CRF)-binding protein (CRF-BP) cDNA and to
      examine the variations in CRF-BP and CRF mRNA levels in response to different
      intensities of stress. Trout were physically disturbed by a single or three
      consecutive periods of chasing until exhaustion followed by 2 h of recovery. The
      pituitary CRF-BP and preoptic area CRF1 mRNA contents were significantly
      increased only after repeated chasing events. Physical disturbance increased
      plasma cortisol levels with the largest change occurring in the group of trout
      that were exposed to repeated chasing events. Trout were also individually
      isolated in 120 l tanks or confined to 1.5 l boxes for 4, 24 or 72 h. CRF-BP mRNA
      levels in confined fish were greater than those of isolated fish at 72 h although
      there were no differences compared with the control group. CRF1 mRNA levels in
      the preoptic area were greater and remained elevated for a longer period in
      confined compared with isolated trout. Isolation led to a transient increase in
      plasma cortisol levels, but the higher cortisol values developed in the confined
      fish suggest that this treatment was more stressful than isolation. These results
      demonstrate that the intensity and duration of stress are important factors
      regulating CRF and CRF-BP mRNA levels in rainbow trout. We hypothesize that
      pituitary CRF-BP is involved in regulating the activity of the stress axis,
      possibly by reducing access to CRF1 receptors in the corticotropes.

PMID- 16002541
TI  - BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary.
AB  - Activins and inhibins, members of the transforming growth factor-beta family are
      able to stimulate and inhibit, respectively, FSH synthesis and release. Other
      members of this superfamily, the bone morphogenetic proteins (BMPs), may also
      affect FSH synthesis in the mouse. The aim of this work was to determine whether
      BMPs are expressed in the ovine pituitary and whether they play a role in the
      regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte
      derived growth factor, growth differentiation factor (GDF)-9 were detected in the
      pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs
      encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3)
      and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary
      sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope
      cells. To investigate the potential effects of BMPs on FSH secretion, ewe
      pituitary cell cultures were treated with BMP-4 (10(-11) M to 10(-9) M) for 48 h.
      Interestingly, FSH release was decreased in a dose-dependent manner. At 10(-9) M
      BMP-4 both FSH concentration and FSHbeta mRNA expression were reduced by 40% of
      control values. In contrast, there was no inhibitory effect on either LH or
      LHbeta mRNA expression. A similar result was found with BMP-6. BMP-4 triggered
      the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH
      secretion is due to the activation of the BMPs signaling pathway. Furthermore,
      BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHbeta
      mRNA and amplified the suppression of FSH release and FSHbeta mRNA levels induced
      by 17beta-estradiol. These results indicate that a functional BMP system operates
      within the sheep pituitary, at least in vitro, to decrease FSH release and to
      modulate the effect of activin.

PMID- 16002544
TI  - Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and
      IGF receptor type 1 mRNA and protein levels in placental and fetal tissues.
AB  - We have previously reported that chronic intra-amniotic supplementation of the
      late gestation growth-restricted (IUGR) ovine fetus with IGF-I (20 microg/day)
      increased gut growth but reduced liver weight and circulating IGF-I
      concentrations. Here we report mRNA and protein levels of IGF-I, the type 1 IGF
      receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1, -2 and -3 in fetal gut,
      liver, muscle and placenta from fetuses in that earlier study in an attempt to
      explain these contrasting results. mRNA and protein were extracted from tissues
      obtained at post mortem at 131 days of gestation (term, 145 days) from three
      groups of fetuses (control, IUGR+saline and IUGR+IGF-I, n=9 per group). Control
      fetuses were unembolised and untreated. In the IUGR groups, growth restriction
      was induced from 113 to 120 days by placental embolisation; from 120 to 130 days
      fetuses were treated with daily intra-amniotic injections of either saline or 20
      microg IGF-I. mRNA was measured by RT-PCR or real-time RT-PCR, and protein by
      Western blot. In liver, muscle and placenta, IGF-I mRNA and protein levels were
      reduced by between 8 and 30% in IGF-I-treated fetuses compared with saline
      treated fetuses and controls with no change in IGF-1R mRNA or protein levels. In
      contrast, in the gut, IGF-I mRNA and protein levels were not significantly
      altered with IGF-I treatment, but IGF-1R levels were increased, especially in the
      jejunum. Immunolocalisation demonstrated that IGF-1R expression was confined to
      the luminal aspect of the gut. mRNA levels of all three IGFBPs were reduced in
      the gut of IGF-I-treated fetuses, but hepatic expression was significantly
      increased. These data demonstrated tissue-specific regulation of IGF-I, IGF-1R
      and IGFBPs-1, -2 and -3 in response to intra-amniotic IGF-I supplementation,
      though the underlying mechanisms remain obscure.

PMID- 16002546
TI  - IGF-I differentially regulates IGF-binding protein expression in primary mammary
      fibroblasts and epithelial cells.
AB  - Elucidating how mitogens facilitate epithelial/stromal interactions is critical
      given that mitogens regulate mammary gland development and function. IGF-I is a
      potent mammary cell mitogen that is locally produced in the mammary gland. Since
      IGF-binding proteins (IGFBPs) regulate IGF-I bioavailability, we characterized
      the cell-type-specific production of IGFBP in primary bovine mammary epithelial
      (BME) and fibroblast (BMF) cells. Cells were treated with IGF-I and mRNA levels
      were analyzed via quantitative real-time (qRT)-PCR and Northern blot analysis.
      Media conditioned by cells treated with IGF-I for 48 h were analyzed via ligand
      blotting with 125I-labeled IGF-I and -II and immunoblotting with specific IGFBP
      antibodies. A reciprocal regulation of IGFBP-3 and -5 by IGF-I was observed
      between the two cell types. IGF-I induced large dose-dependent increases in IGFBP
      3 mRNA and protein levels in BME cells, while IGFBP-5 protein was barely
      detectable and mRNA levels were detectable only by qRT-PCR. In BMFs, IGF-I
      induced large increases in IGFBP-5 mRNA and protein while IGFBP-3 mRNA was only
      slightly increased by IGF-I treatment and the protein was difficult to detect.
      IGFBP-6 mRNA was detected by Northern blot analysis in both cell types but was
      not regulated by IGF-I. In BME cells, IGFBP-6 protein levels were readily
      detectable under basal conditions and were increased by IGF-I. Interestingly,
      IGFBP-6 protein could not be detected in media conditioned by BMFs. IGFBP-4 mRNA
      was readily seen by Northern blot analysis in BMFs, however qRT-PCR was required
      to detect IGFBP-4 mRNA in BME cells. IGF-I increased IGFBP-4 mRNA levels by 2
      fold in both cell types. IGFBP-4 protein was only detectable in media conditioned
      by BME cells when stimulated by IGF-I. In contrast, IGFBP-4 was present in media
      conditioned by untreated BMFs but was not consistently increased by IGF-I
      treatment. This was explained by the finding that IGF-I stimulated proteolysis of
      IGFBP-4, as evidenced by the appearance of two immuno-responsive fragments of 18
      and 14 kDa. This proteolysis was specific to IGFBP-4, and was not observed in BME
      cells. We confirmed the protease to be pregnancy-associated plasma protein A
      (PAPP-A) by immunoblotting with an antibody against human PAPP-A/proMBP (pro form
      of eosinophil major basic protein) complex. In vitro immuno-neutralization
      experiments showed that blocking PAPP-A prevented the ability of IGF-I to
      stimulate IGFBP-4 proteolysis. IGFBP-2 mRNA and protein levels were observed
      under basal conditions in both cell types, with no significant regulation by IGF
      I. The analysis of cell-type-specific regulation of the IGF system in both
      primary mammary epithelial cells and stromal cells will assist in the
      characterization of the mechanisms behind the role of the IGF system in normal
      mammary physiology and ultimately breast cancer.

PMID- 16002545
TI  - Effects of 5'-uridylic acid feeding on postprandial plasma concentrations of GH,
      insulin and metabolites in young calves.
AB  - Postprandial changes in plasma concentrations of GH, insulin, IGF-I, leptin and
      metabolites were compared between young Holstein bull calves fed with milk alone
      (control group) and with milk+5'-uridylic acid (UMP) (UMP group). UMP (2 g/day)
      was given with milk at 0830 h and 1530 h for 11 days from the 4th to the 14th day
      after birth. The perirenal fat weight was significantly lower in the UMP group
      than in the control group, but there was no significant difference in the weights
      of the liver, spleen and heart between the groups. Basal GH concentrations in the
      UMP group were slightly higher, but the postprandial increase in plasma insulin
      level and the area under the curve for insulin in the UMP group were
      significantly lower than those in the control group. There was no significant
      difference in IGF-I levels between the groups. In addition, the postprandial
      glucose concentrations were lower in the UMP group as reflected by the insulin
      level, and nonesterified fatty acid concentrations were not different. In the
      muscle (M. longissimus thoracis) sampled at 14 days of age, the triacylglycerol
      (TAG) content was significantly greater but glycogen content was significantly
      lower in the UMP group than in the control group. From these results, we have
      concluded that feeding 5'-UMP at 2 g/day for 11 days significantly alters TAG
      accumulation in the body and plasma concentrations of GH and insulin in young
      bull calves.

PMID- 16002547
TI  - Role of Cdx-2 in insulin and proglucagon gene expression: a study using the RIN
      1056A cell line with an inducible gene expression system.
AB  - Although the homeobox gene Cdx-2 was initially isolated from the pancreatic beta
      cell line HIT-T15, no examination of its role in regulating endogenous insulin
      gene expression has been reported. To explore further the role of Cdx-2 in
      regulating both insulin and proglucagon gene expression, we established an
      ecdysone-inducible Cdx-2 expression system. This report describes a study using
      the rat insulinoma cell line RIN-1056A, which abundantly expresses both insulin
      and proglucagon (glu), and relatively high amounts of endogenous Cdx-2. Following
      the introduction of the inducible Cdx-2 expression system into this cell line and
      the antibiotic selection procedure, we obtained novel cell lines that displayed
      dramatically reduced expression of endogenous Cdx-2, in the absence of the
      inducer. These novel cell lines did not express detectable amounts of glu mRNA or
      the glucagon hormone, while their insulin expression was not substantially
      affected. In the presence of the inducer, however, transfected Cdx-2 expression
      was dramatically increased, accompanied by stimulation of endogenous Cdx-2
      expression. More importantly, activated Cdx-2 expression was accompanied by
      elevated insulin mRNA expression, and insulin synthesis. Cdx-2 bound to the
      insulin gene promoter enhancer elements, and stimulated the expression of a
      luciferase reporter gene driven by these enhancer elements. Furthermore, Cdx-2
      and insulin gene expressions in the wild-type RIN-1056A cells were stimulated by
      forskolin treatment, and forskolin-mediated activation on insulin gene expression
      was attenuated in the absence of Cdx-2. We suggest that Cdx-2 may mediate the
      second messenger cAMP in regulating insulin gene transcription.

PMID- 16002549
TI  - Adipose tissue transplantation protects ob/ob mice from obesity, normalizes
      insulin sensitivity and restores fertility.
AB  - Adipose tissue affects metabolism by secreting various adipokines. Lipodystropic
      mice benefit both from leptin replacement therapy and from transplantation of
      normal fat. Leptin-deficient Lep(ob)/Lep(ob) (ob/ob) mice can also be treated
      with leptin. Surprisingly, there have been no reports of successful treatment of
      obese ob/ob mice by transplantation of normal white adipose tissue (WAT). If WAT
      transplantation is ineffective in treating insulin resistance and diabetes in
      obese individuals, its applicability may be limited in humans as such
      abnormalities are usually associated with obesity. In the current study, we
      tested whether WAT transplantation might prevent, and even reverse, abnormalities
      characteristic of ob/ob mice. To assess the preventive potential, 6-week-old
      ob/ob mice were transplanted, subcutaneously, with gonadal fat pads from normal
      mice. Profound effects on multiple physiological phenotypes were achieved despite
      leptin levels below 25% of those in control mice. WAT from one donor reduced body
      weight gain, and WAT from 4 or 8 donors prevented obesity in ob/ob mice.
      Nonfasting insulin levels and insulin tolerance test were normalized.
      Corticosterone elevation was also prevented. Finally, WAT from 4 donors restored
      fertility in ob/ob females. The effects of WAT transplantation were long-lasting,
      with body weight gain suppressed for at least 40 weeks. To assess the therapeutic
      potential, obese 13-month-old ob/ob mice with a long history of leptin deficiency
      were used. Their body weight decreased by approximately 50% when transplanted
      with WAT from 8 donors. As in young recipients, transplantation greatly reduced
      nonfasting insulin, suggesting normalized insulin sensitivity. Thus, WAT
      transplantation was effective for both prevention and therapy. In the future, WAT
      transplantation may become a useful alternative to hormone replacement in
      treating not only lipodystropy, but also certain types of obesity.

PMID- 16002548
TI  - Melanin-concentrating hormone induces insulin resistance through a mechanism
      independent of body weight gain.
AB  - Transgenic hyperexpression of melanin-concentrating hormone (MCH) produces a
      phenotype of obesity and glucose intolerance. However, it is not known whether
      under this specific condition, glucose intolerance develops as a direct
      consequence of hyperexpressed MCH or is secondary to increased adiposity. Here,
      rats were treated i.c.v. with MCH or with an antisense oligonucleotide to MCH
      (MCH-ASO). MCH promoted an increase in blood glucose and a decrease in blood
      insulin levels during a glucose tolerance test. MCH also caused a decrease in the
      constant of glucose disappearance during an insulin tolerance test. All these
      effects of MCH were independent of body weight variation and were accompanied by
      reduced insulin receptor substrate (IRS)-1 engagement of phosphatidylinositol-3
      kinase (PI3-kinase) in white and brown adipose tissues, skeletal muscle and liver
      and by reduced Akt activation in skeletal muscle. MCH also led to a significant
      reduction in ERK activation in white adipose tissue. Finally, inhibition of
      hypothalamic MCH expression promoted a significant increase in ERK activation in
      brown adipose tissue. We conclude that hypothalamic MCH controls glucose
      homeostasis through mechanisms that are, at least in part, independent of
      adiposity.

PMID- 16002550
TI  - Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS
      1 cell clone transplantation and the deleterious effects of the drugs are
      limited: in vivo and in vitro studies.
AB  - One of the major requirements for a successful and life-lasting organ transplant
      is the access to safe, least toxic and permanent tolerance-inducing drugs. In
      this study we wished to evaluate the effects of tolerogenic doses of the
      immunosuppressive drugs mycophenolic acid (MPA) and tacrolimus (Tac) on clonal
      beta-cell lines, both in vivo and in vitro. Here we demonstrate that combined
      administration of low-dose MPA and Tac for 23 days induced permanent tolerance in
      an allogeneic beta-cell line transplant in Wistar rat liver through the portal
      vein. This short-term treatment of tolerogenic doses of the two drugs was
      deleterious to the survival of the transplanted cells but a small percentage of
      the cells could resist the effect and become fully active when the drugs were
      removed. The surviving cells, retrieved from growth in vivo, did not exhibit
      increased resistance in comparison to the original cells when tested in vitro at
      two glucose concentrations, 10 and 20 mM. The presence of a small percentage of
      resistant cells at the two glucose concentrations was also detected in the in
      vitro study after a continuous 8-day treatment demonstrating that the in vivo
      resistance was not related to micro-environmental protection but possibly to a
      phenotypic cell state that is yet to be determined.

PMID- 16002551
TI  - The cytoplasmic domain close to the transmembrane region of the glucagon-like
      peptide-1 receptor contains sequence elements that regulate agonist-dependent
      internalisation.
AB  - In order to gain better insight into the molecular events involved in the signal
      transduction generated through glucagon-like peptide-1 (GLP-1) receptors, we
      tested the effect of deletions and point mutations within the cytoplasmic tail of
      this receptor with a view to establishing relationships between signal
      transduction desensitisation and receptor internalisation. Wild-type and
      truncated (deletion of the last 27 amino acids (GLPR 435R) and deletion of 44
      amino acids (GLPR 418R)) GLP-1 receptors bound the agonist with similar affinity.
      Deletion of the last 27 amino acids decreased the internalisation rate by 78%,
      while deletion of 44 amino acids containing all the phosphorylation sites
      hitherto described in this receptor decreased the internalisation rate by only
      47%. Binding of the ligand to both receptors stimulated adenylyl cyclase. In
      contrast, deletion of the region containing amino acids 419 to 435 (GLPR
      419delta435) increased the internalisation rate by 268%, and the replacement of
      EVQ(408-410) by alanine (GLPR A(408-410)) increased this process to 296%. In both
      receptors, the efficacy in stimulating adenylate cyclase was decreased. All the
      receptors studied were internalised by coated pits, except for the receptor with
      a deletion of the last 44 amino acids, which also had a faster resensitisation
      rate. Our findings indicate that the neighbouring trans-membrane domain of the
      carboxyl-terminal tail of the GLP-1 receptor contains sequence elements that
      regulate agonist-dependent internalisation and transmembrane signalling.

PMID- 16002552
TI  - Stimulation of catecholamine biosynthesis via the PKC pathway by prolactin
      releasing peptide in PC12 rat pheochromocytoma cells.
AB  - We have previously shown that prolactin-releasing peptide (PrRP) stimulates
      catecholamine release from PC12 cells (rat pheochromocytoma cell line). However,
      it is not known whether PrRP also affects catecholamine biosynthesis. Thus, we
      examined the effect of PrRP on catecholamine biosynthesis in PC12 cells. PrRP31
      (>10 nM) and PrRP20 (>100 nM) significantly increased the activity and expression
      level of tyrosine hydroxylase (TH), a rate-limiting enzyme, in catecholamine
      biosynthesis. However, the PrRP20-stimulated TH activity was markedly weaker than
      that of PrRP31. PrRP31 (>1 nM) and PrRP20 (>10 nM) significantly induced an
      increase in the level of PKC activity. Both Ro 32-0432 (a protein kinase C
      inhibitor) and H89 (a protein kinase A inhibitor) effectively suppressed the
      PrRP31 (100 nM)-induced TH mRNA level. Next, we examined the effect of PrRP on
      mitogen-activated protein kinases (MAPKs). PrRP31 (1 microM) significantly
      induced an increase in the activity of extracellular signal-related kinases
      (ERKs) and the stress-activated protein kinase/c-jun N terminal kinase
      (SAPK/JNK). In contrast to ERKs and JNK, PrRP31 did not affect P38 MAPK activity.
      Consistent with these findings, pretreatment of cells with the MEK-1-inhibitor,
      PD-98059 (50 microM), significantly inhibited the PrRP31 (100 nM)-induced
      increase in TH mRNA. These results indicate that PrRP stimulates catecholamine
      synthesis through both the PKC and PKA pathways in PC12 cells.

PMID- 16002553
TI  - Growth plate senescence is associated with loss of DNA methylation.
AB  - The overall body size of vertebrates is primarily determined by longitudinal bone
      growth at the growth plate. With age, the growth plate undergoes programmed
      senescence, causing longitudinal bone growth to slow and eventually cease.
      Indirect evidence suggests that growth plate senescence occurs because stem-like
      cells in the growth plate resting zone have a finite proliferative capacity that
      is gradually exhausted. Similar limits on replication have been observed when
      many types of animal cells are placed in cell culture, an effect known as the
      Hayflick phenomenon. However, we found that the number of population doublings of
      rabbit resting zone chondrocytes in culture did not depend on the age of the
      animal from which the cells were harvested, suggesting that the mechanisms
      limiting replicative capacity of growth plate chondrocytes in vivo are distinct
      from those in vitro. We also observed that the level of DNA methylation in
      resting zone chondrocytes decreased with age in vivo. This loss of methylation
      appeared to occur specifically with the slow proliferation of resting zone
      chondrocytes in vivo and was not observed with the rapid proliferation of
      proliferative zone chondrocytes in vivo (i.e. the level of DNA methylation did
      not change from the resting zone to the hypertrophic zone), with proliferation of
      chondrocytes in vitro, or with growth of the liver in vivo. Thus, the overall
      level of DNA methylation decreases during growth plate senescence. This finding
      is consistent with the hypothesis that the mechanism limiting replication of
      growth plate chondrocytes in vivo involves loss of DNA methylation and, thus,
      loss of DNA methylation might be a fundamental biological mechanism that limits
      longitudinal bone growth in mammals, thereby determining the overall adult size
      of the organism.

PMID- 16002554
TI  - Vasoconstriction during venous congestion: effects of venoarteriolar response,
      myogenic reflexes, and hemodynamics of changing perfusion pressure.
AB  - We dissected the relative contribution of arteriovenous hemodynamics, the
      venoarteriolar response (VAR), and the myogenic reflex toward a decrease in local
      blood flow induced by venous congestion. Skin blood flow (SkBF) was measured in
      12 supine subjects via laser-Doppler flowmetry 1) over areas of forearm and calf
      skin, in which the VAR was blocked by using eutectic mixture of local anesthetics
      (EMLA sites) and 2) over the contralateral forearm or calf skin (control sites),
      using two different techniques: limb dependency of 23-37 cm below the heart and
      cuff inflation to 40 mmHg. During limb dependency, SkBF decreased at the control
      sites, whereas it remained unchanged at the EMLA sites. In contrast, during cuff
      inflation, SkBF decreased at the control sites and also decreased at the EMLA
      sites. The percent change in SkBF from baseline was greater during cuff inflation
      than limb dependency at both the control sites and the EMLA sites. Estimated skin
      vascular resistance remained unchanged at the EMLA sites during cuff inflation,
      as well as limb dependency. Thus the decrease in SkBF during venous congestion
      with cuff inflation is not solely due to the cutaneous VAR but also to a
      reduction in local perfusion pressure. The VAR is therefore most specifically
      quantified by venous congestion induced by limb dependency, rather than cuff
      inflation. Finally, from both techniques, we calculated that during venous
      congestion induced by limb dependency (calf), approximately 45% of the
      nonbaroreflex vasoconstriction is induced by the VAR and approximately 55% by the
      myogenic reflex.

PMID- 16002555
TI  - Light induces c-fos and per1 expression in the suprachiasmatic nucleus of
      arrhythmic hamsters.
AB  - Locomotor activity rhythms in a significant proportion of Siberian hamsters
      (Phodopus sungorus sungorus) become arrhythmic after the light-dark (LD) cycle is
      phase-delayed by 5 h. Arrhythmia is apparent within a few days and persists
      indefinitely despite the presence of the photocycle. The failure of arrhythmic
      hamsters to regain rhythms while housed in the LD cycle, as well as the lack of
      any masking of activity, suggested that the circadian system of these animals had
      become insensitive to light. We tested this hypothesis by examining light-induced
      gene expression in the suprachiasmatic nucleus (SCN). Several weeks after the
      phase delay, arrhythmic and re-entrained hamsters were housed in constant
      darkness (DD) for 24 h and administered a 30-min light pulse 2 h after predicted
      dark onset because light induces c-fos and per1 genes at this time in entrained
      animals. Brains were then removed, and tissue sections containing the SCN were
      processed for in situ hybridization and probed with c-fos and per1 mRNA probes
      made from Siberian hamster cDNA. Contrary to our prediction, light pulses induced
      robust expression of both c-fos and per1 in all re-entrained and arrhythmic
      hamsters. A separate group of animals held in DD for 10 days after the light
      pulse remained arrhythmic. Thus, even though the SCN of these animals responded
      to light, neither the LD cycle nor DD restored rhythms, as it does in other
      species made arrhythmic by constant light (LL). These results suggest that
      different mechanisms underlie arrhythmicity induced by LL or by a phase delay of
      the LD cycle. Whereas LL induces arrhythmicity by desynchronizing SCN neurons,
      phase delay-induced arrhythmicity may be due to a loss of circadian rhythms at
      the level of individual SCN neurons.

PMID- 16002556
TI  - Deficiency of alpha-sarcoglycan differently affects fast- and slow-twitch
      skeletal muscles.
AB  - Alpha-sarcoglycan (Sgca) is a transmembrane glycoprotein of the dystrophin
      complex located at skeletal and cardiac muscle sarcolemma. Defects in the alpha
      sarcoglycan gene (Sgca) cause the severe human-type 2D limb girdle muscular
      dystrophy. Because Sgca-null mice develop progressive muscular dystrophy similar
      to human disorder they are a valuable animal model for investigating the
      physiopathology of the disorder. In this study, biochemical and functional
      properties of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus
      muscles of the Sgca-null mice were analyzed. EDL muscle of Sgca-null mice showed
      twitch and tetanic kinetics comparable with those of wild-type controls. In
      contrast, soleus muscle showed reduction of twitch half-relaxation time,
      prolongation of tetanic half-relaxation time, and increase of maximal rate of
      rise of tetanus. EDL muscle of Sgca-null mice demonstrated a marked reduction of
      specific twitch and tetanic tensions and a higher resistance to fatigue compared
      with controls, changes that were not evident in dystrophic soleus. Contrary to
      EDL fibers, soleus muscle fibers of Sgca-null mice distinctively showed right
      shift of the pCa-tension (pCa is the negative log of Ca2+ concentration)
      relationships and reduced sensitivity to caffeine of sarcoplasmic reticulum. Both
      EDL and soleus muscles showed striking changes in myosin heavy-chain (MHC)
      isoform composition, whereas EDL showed a larger number of hybrid fibers than
      soleus. In contrast to the EDL, soleus muscle of Sgca-null mice contained a
      higher number of regenerating fibers and thus higher levels of embryonic MHC. In
      conclusion, this study revealed profound distinctive biochemical and
      physiological modifications in fast- and slow-twitch muscles resulting from alpha
      sarcoglycan deficiency.

PMID- 16002557
TI  - Ontogeny and nutritional programming of adiposity in sheep: potential role of
      glucocorticoid action and uncoupling protein-2.
AB  - Increased glucocorticoid action and adipose tissue inflammation contribute to
      excess adiposity. These adaptations may be enhanced in offspring exposed to
      nutrient restriction (NR) in utero, thereby increasing their susceptibility to
      later obesity. We therefore determined the developmental ontogeny of
      glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase (11betaHSD)
      types 1 and 2, and uncoupling protein (UCP)-2 mRNA in perirenal adipose tissue
      between late gestation and 6 mo after birth in the sheep, as well as the effect
      of maternal NR targeted between early to mid (28-80 days, term approximately 147
      days)- or late (110-147 days) gestation. GR and 11betaHSD1 mRNA increased with
      fat mass and were all maximal within the 6-mo observation period. 11betaHSD2 mRNA
      abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and
      11betaHSD1 mRNA abundance were strongly correlated with total and relative
      perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and
      11betaHSD1 mRNA. Early- to midgestational NR increased GR, 11betaHSD1, and UCP2
      mRNA, but decreased 11betaHSD2 mRNA abundance, an adaptation reversed with late
      gestational NR. We conclude that the continual rise in glucocorticoid action and
      fat mass after birth may underlie the development of later obesity. The magnitude
      of this adaptation is partly dependent on maternal food intake through pregnancy.

PMID- 16002558
TI  - Effect of histamine and cimetidine on retinal and choroidal blood flow in humans.
AB  - Intravenous administration of histamine causes an increase in choroidal blood
      flow and retinal vessel diameter in healthy subjects. The mechanism underlying
      this effect remains to be elucidated. In the present study, we hypothesized that
      H2 receptor blockade alters hemodynamic effects of histamine in the choroid and
      retina. Eighteen healthy male nonsmoking volunteers were included in this
      randomized, double-masked, placebo-controlled two-way crossover study. Histamine
      (0.32 microg.kg(-1).min(-1) over 30 min) was infused intravenously in the absence
      (NaCl as placebo) or presence of the H2 blocker cimetidine (2.3 mg/min over 50
      min). Ocular hemodynamic parameters, blood pressure, and intraocular pressure
      were measured before drug administration, after infusion of cimetidine or
      placebo, and after coinfusion of histamine. Subfoveal choroidal blood flow and
      fundus pulsation amplitude were measured with laser-Doppler flowmetry and laser
      interferometry, respectively. Retinal arterial and venous diameters were measured
      with a retinal vessel analyzer. Retinal blood velocity was assessed with
      bidirectional laser-Doppler velocimetry. Histamine increased subfoveal choroidal
      blood flow (+14 +/- 15%, P < 0.001), fundus pulsation amplitude (+11 +/- 5%, P <
      0.001), retinal venous diameter (+3.0 +/- 3.6%, P = 0.002), and retinal arterial
      diameter (+2.8 +/- 4.2%, P < 0.01) but did not change retinal blood velocity. The
      H2 antagonist cimetidine had no significant effect on ocular hemodynamic
      parameters. In addition, cimetidine did not modify effects of histamine on
      choroidal blood flow, fundus pulsation amplitude, retinal venous diameter, and
      retinal arterial diameter compared with placebo. The present data confirm that
      histamine increases choroidal blood flow and retinal vessel diameters in healthy
      subjects. This ocular vasodilator effect of histamine is, however, not altered by
      administration of an H2 blocker. Whether the increase in blood flow is mediated
      via H1 receptors or other hitherto unidentified mechanisms remains to be
      elucidated.

PMID- 16002559
TI  - Augmented responses to ozone in obese carboxypeptidase E-deficient mice.
AB  - We reported previously that mice obese as a result of leptin deficiency (ob/ob)
      have enhanced ozone (O3)-induced airway hyperresponsiveness (AHR) and
      inflammation compared with wild-type (C57BL/6) controls. To determine whether
      this increased response to O3 was independent of the modality of obesity, we
      examined O3-induced AHR and inflammation in Cpe(fat) mice. These mice are obese
      as a consequence of a mutation in the gene encoding carboxypeptidase E (Cpe), an
      enzyme important in processing prohormones and proneuropeptides involved in
      satiety and energy expenditure. Airway responsiveness to intravenous
      methacholine, measured by forced oscillation, was increased in Cpe(fat) vs. wild
      type mice after air exposure. In addition, compared with air exposure, airway
      responsiveness was increased 24 h after O3 exposure (2 ppm for 3 h) in Cpe(fat)
      but not in wild-type mice. Compared with air-exposed controls, O3 exposure
      increased bronchoalveolar lavage fluid (BALF) protein, IL-6, KC, MIP-2, MCP-1,
      and soluble TNF receptors (sTNFR1 and sTNFR2) as well as BALF neutrophils. With
      the exception of sTNFR1 and sTNFR2, all of these outcome indicators were greater
      in Cpe(fat) vs. wild-type mice. Serum sTNFR1, sTNFR2, MCP-1, leptin, and blood
      leukocytes were elevated in Cpe(fat) compared with wild-type mice even in the
      absence of O3 exposure, similar to the chronic systemic inflammation observed in
      human obesity. These results indicate that increased O3-induced AHR and
      inflammation are consistent features of obese mice, regardless of the modality of
      obesity. These results also suggest that chronic systemic inflammation may
      enhance airway responses to O3 in obese mice.

PMID- 16002560
TI  - Uteroplacental insufficiency alters hepatic expression, phosphorylation, and
      activity of the glucocorticoid receptor in fetal IUGR rats.
AB  - Uteroplacental insufficiency (UPI) induces persistent changes in hepatic gene
      expression secondary to altered chromatin dynamics in the intrauterine growth-
      restricted (IUGR) rat liver. The glucocorticoid receptor (GR) is a transcription
      factor that when activated can induce changes in chromatin structure. To begin
      the process of identifying pathways by which IUGR affects chromatin structure, we
      hypothesized that UPI in the rat induces a significant increase in endogenous
      glucocorticoids (corticosterone) and increases GR expression and activation. To
      prove our hypothesis, we induced IUGR through bilateral uterine artery ligation
      of the pregnant rat. At day 1, UPI significantly increased corticosterone levels
      and was associated with increased total GR mRNA and protein levels in the liver,
      as well as increased hepatic phosphorylation of GR serine 211. Moreover, cyclin
      dependent kinase 2 (CDK2) cyclinA/CDK2 protein levels, which selectively
      phosphorylate GR serine 211, were also significantly increased. To assess
      activity of the GR, we measured protein levels of the transcription factor p53
      whose levels are downregulated, at least in part, by active GR. In this study,
      UPI decreased p53 protein and its downstream target Bax mRNA levels. We conclude
      that UPI in rats affects GR expression and activity in the liver. We speculate
      that these alterations early in life may contribute to the changes in chromatin
      structure and gene expression previously described in the IUGR liver.

PMID- 16002561
TI  - Role of PKC in the regulation of gonadotropin subunit mRNA levels: interaction
      with two native forms of gonadotropin-releasing hormone.
AB  - Gonadotropin-releasing hormone (GnRH) is an important regulator of reproduction
      in all vertebrates through its actions on the production and secretion of
      pituitary gonadotropin hormones (GtHs). Most vertebrate species express at least
      two GnRHs, including one form, designated chicken (c)GnRH-II or type II GnRH,
      which has been well conserved throughout evolution. The goldfish brain and
      pituitary contain salmon GnRH and cGnRH-II. In goldfish, GnRH-induced luteinizing
      hormone (LH) secretion involves PKC; however, whether PKC mediates GnRH
      stimulation of GtH subunit mRNA levels is unknown. In this study, we used
      inhibitors and activators of PKC to examine its possible involvement in GnRH
      induced increases in GtH-alpha, follicle-stimulating hormone (FSH)-beta and LH
      beta mRNA levels in primary cultures of dispersed goldfish pituitary cells.
      Treatment with PKC inhibitors calphostin C and GF109203X unmasked a basal
      repression of GtH subunit mRNA levels by PKC; both inhibitors increased GtH
      subunit mRNA levels in a dose-dependent manner. PKC activators, 12-O
      tetradecanoylphorbol 13-acetate (TPA), and 1,2-dioctanoyl-sn-glycerol, stimulated
      GtH subunit mRNA levels, whereas an inactive phorbol ester (4-alpha-TPA) was
      without effect. Thus, a dual, inhibitory and stimulatory, influence for PKC in
      the regulation of GtH subunit mRNA levels is suggested. In contrast, PKC
      inhibitor- and activator-induced effects were, for the most part, additive to
      those of GnRH, suggesting that conventional and novel PKCs are unlikely to be
      involved in GnRH-stimulated increases in GtH subunit mRNA levels. Our data
      illustrate major differences in the signal transduction of GnRH effects on GtH
      secretion and gene expression in the goldfish pituitary.

PMID- 16002563
TI  - Inhibition of lymphocyte apoptosis by pancreatic stellate cells: impact of
      interleukin-15.
AB  - There is growing evidence that pancreatic stellate cells (PSCs) produce cytokines
      and take part in the regulation of inflammatory processes in the pancreas. IL-15
      inhibits apoptosis of various cell populations. This study was performed to
      investigate whether PSCs produce IL-15 and thereby can affect lymphocytes.
      Primary PSCs were isolated from the rat pancreas using density gradient
      centrifugation. mRNA expression of IL-15 was demonstrated by RT-PCR, and IL-15
      protein was analyzed by immunoblotting. Lymphocytes obtained from rat mesenterial
      lymph nodes were cocultured with in vitro activated PSCs. Apoptosis has been
      quantified by the binding of annexin V-FITC with a flow cytometer. Proliferation
      was monitored using [3H]thymidine incorporation. PSCs express two splice variants
      of IL-15. The protein was detectable only in cell lysates but not in the cell
      culture supernatant. Cocultivation of lymphocytes with PSCs and IL-15 inhibited
      spontaneous lymphocyte apoptosis, and this effect was reduced by an anti-IL-15
      antibody. Lymphocytes induced vice versa the proliferation and collagen
      production of PSCs. The inhibition of spontaneous lymphocyte apoptosis in
      cocultures with PSCs was at least partially mediated by cell-bound IL-15. This
      effect and the stimulation of PSCs by lymphocytes may lead to a circulus
      vitiosus, resulting in the persistence of inflammatory processes and the
      development of fibrosis during chronic pancreatitis.

PMID- 16002562
TI  - Intracellular Ca(2+) and Zn(2+) signals during monochloramine-induced oxidative
      stress in isolated rat colon crypts.
AB  - During acute exacerbations of inflammatory bowel diseases, oxidants are generated
      through the interactions of bacteria in the lumen, activated granulocytes, and
      cells of the colon mucosa. In this study we explored the ability of one such
      class of oxidants, represented by monochloramine (NH(2)Cl), to serve as agonists
      of Ca(2+) and Zn(2+) accumulation within the colonocyte. Individual colon crypts
      prepared from Sprague-Dawley rats were mounted in perfusion chambers after
      loading with fluorescent reporters fura 2-AM and fluozin 3-AM. These reporters
      were characterized, in situ, for responsiveness to Ca(2+) and Zn(2+) in the
      cytoplasm. Responses to different concentrations of NH(2)Cl (50, 100, and 200
      microM) were monitored. Subsequent studies were designed to identify the sources
      and mechanisms of NH(2)Cl-induced increases in Ca(2+) and Zn(2+) in the
      cytoplasm. Exposure to NH(2)Cl led to dose-dependent increases in intracellular
      Ca(2+) concentration ([Ca(2+)](i)) in the range of 200-400 nM above baseline
      levels. Further studies indicated that NH(2)Cl-induced accumulation of Ca(2+) in
      the cytoplasm is the result of release from intracellular stores and basolateral
      entry of extracellular Ca(2+) through store-operated channels. In addition,
      exposure to NH(2)Cl resulted in dose-dependent and sustained increases in
      intracellular Zn(2+) concentration ([Zn(2+)](i)) in the nanomolar range. These
      alterations were neutralized by dithiothreitol, which shields intracellular thiol
      groups from oxidation. We conclude that Ca(2+)- and Zn(2+)-handling proteins are
      susceptible to oxidation by chloramines, leading to sustained, but not
      necessarily toxic, increases in [Ca(2+)](i) and [Zn(2+)](i). Under certain
      conditions, NH(2)Cl may act not as a toxin but as an agent that activates
      intracellular signaling pathways.

PMID- 16002564
TI  - Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is
      bicarbonate dependent.
AB  - Normal human colonic luminal (NH(4)(+)) concentration ([NH(4)(+)]) ranges from
      approximately 10 to 100 mM. However, the nature of the effects of NH(4)(+) on
      transport, as well as NH(4)(+) transport itself, in colonic epithelium is poorly
      understood. We elucidate here the effects of apical NH(4)(+) on cAMP-stimulated
      Cl(-) secretion in colonic T84 cells. In HEPES-buffered solutions, 10 mM apical
      NH(4)(+) had no significant effect on cAMP-stimulated current. In contrast, 10 mM
      apical NH(4)(+) reduced current within 5 min to 61 +/- 4% in the presence of 25
      mM HCO(3)(-). Current inhibition was not simply due to an increase in
      extracellular K(+)-like cations, in that the current magnitude was 95 +/- 5% with
      10 mM apical K(+) and 46 +/- 3% with 10 mM apical NH(4)(+) relative to that with
      5 mM apical K(+). We previously demonstrated that inhibition of Cl(-) secretion
      by basolateral NH(4)(+) occurs in HCO(3)(-)-free conditions and exhibits
      anomalous mole fraction behavior. In contrast, apical NH(4)(+) inhibition of
      current in HCO(3)(-) buffer did not show anomalous mole fraction behavior and
      followed the absolute [NH(4)(+)] in K(+)-NH(4)(+) mixtures, where K(+)
      concentration + [NH(4)(+)] = 10 mM. The apical NH(4)(+) inhibitory effect was not
      prevented by 100 microM methazolamide, suggesting no role for apical carbonic
      anhydrase. However, apical NH(4)(+) inhibition of current was prevented by 10 min
      of pretreatment of the apical surface with 500 microM DIDS, 100 microM 4,4'
      dinitrostilbene-2,2'-disulfonic acid (DNDS), or 25 microM niflumic acid,
      suggesting a role for NH(4)(+) action through an apical anion exchanger. mRNA and
      protein for the apical anion exchangers SLC26A3 [downregulated in adenoma (DRA)]
      and SLC26A6 [putative anion transporter (PAT1)] were detected in T84 cells by RT
      PCR and Northern and Western blots. DRA and PAT1 appear to associate with CFTR in
      the apical membrane. We conclude that the HCO(3)(-) dependence of apical NH(4)(+)
      inhibition of secretion is due to the action of NH(4)(+) on an apical anion
      exchanger.

PMID- 16002565
TI  - Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp
      repression in biliary obstruction in mouse liver.
AB  - Expression of the main hepatic bile acid uptake system, the Na+-taurocholate
      cotransporter (Ntcp), is downregulated during cholestasis. Bile acid-induced,
      farnesoid X receptor (FXR)-mediated induction of the nuclear repressor short
      heterodimer partner (SHP) has been proposed as a key mechanism reducing Ntcp
      expression. However, the role of FXR and SHP or other nuclear receptors and
      hepatocyte-enriched transcription factors in mediating Ntcp repression in
      obstructive cholestasis is unclear. FXR knockout (FXR-/-) and wild-type (FXR+/+)
      mice were subjected to common bile duct ligation (CBDL). Cholic acid (CA)-fed and
      LPS-treated FXR-/- and FXR+/+ mice were studied for comparison. mRNA levels of
      Ntcp and SHP and nuclear protein levels of hepatocyte nuclear factor (HNF)
      1alpha, HNF-3beta, HNF-4alpha, retinoid X receptor (RXR)-alpha, and retinoic acid
      receptor (RAR)-alpha and their DNA binding were assessed. Hepatic cytokine mRNA
      levels were also measured. CBDL and CA led to Ntcp repression in FXR+/+, but not
      FXR-/-, mice, whereas LPS reduced Ntcp expression in both genotypes. CBDL and LPS
      but not CA induced cytokine expression and reduced levels of HNF-1alpha, HNF
      3beta, HNF-4alpha, RXRalpha, and RARalpha to similar extents in FXR+/+ and FXR-/
      . DNA binding of these transactivators was unaffected by CA in FXR+/+ mice but
      was markedly reduced in FXR-/- mice. In conclusion, Ntcp repression by CBDL and
      CA is mediated by accumulating bile acids via FXR and does not depend on
      cytokines, whereas Ntcp repression by LPS is independent of FXR. Reduced levels
      of HNF-1alpha, RXRalpha, and RARalpha in CBDL FXR-/- mice and reduced DNA binding
      in CA-fed FXR-/- mice, despite unchanged Ntcp levels, indicate that these factors
      may have a minor role in regulation of mouse Ntcp during cholestasis.

PMID- 16002566
TI  - Divergent functions of CD4+ T lymphocytes in acute liver inflammation and injury
      after ischemia-reperfusion.
AB  - Hepatic ischemia-reperfusion results in an acute inflammatory response
      culminating in the recruitment of activated neutrophils that directly injure
      hepatocytes. Recent evidence suggests that CD4+ lymphocytes may regulate this
      neutrophil-dependent injury, but the mechanisms by which this occurs remain to be
      elucidated. In the present study, we sought to determine the type of CD4+
      lymphocytes recruited to the liver after ischemia-reperfusion and the manner in
      which these cells regulated neutrophil recruitment and tissue injury. Wild-type
      and CD4 knockout (CD4-/-) mice were subjected to hepatic ischemia-reperfusion.
      CD4+ lymphocytes were recruited in the liver within 1 h of reperfusion and
      remained for at least 4 h. These cells were comprised of conventional
      (alphabetaTCR-expressing), unconventional (gammadeltaTCR-expressing), and natural
      killer T cells. CD4-/- mice were then used to determine the functional role of
      CD4+ lymphocytes in hepatic ischemia-reperfusion injury. Compared with wild-type
      mice, CD4-/- mice had significantly greater liver injury, yet far less neutrophil
      accumulation. Adoptive transfer of CD4+ lymphocytes to CD4-/- mice recapitulated
      the wild-type response. In wild-type mice, neutralization of interleukin (IL)-17,
      a cytokine released by activated CD4+ lymphocytes, significantly reduced
      neutrophil recruitment in association with suppression of MIP-2 expression.
      Finally, oxidative burst activity of liver-recruited neutrophils was higher in
      CD4-/- mice compared with those from wild-type mice. These data suggest that CD4+
      lymphocytes are rapidly recruited to the liver after ischemia-reperfusion and
      facilitate subsequent neutrophil recruitment via an IL-17-dependent mechanism.
      However, these cells also appear to attenuate neutrophil activation. Thus the
      data suggest that CD4+ lymphocytes have dual, opposing roles in the hepatic
      inflammatory response to ischemia-reperfusion.

PMID- 16002567
TI  - Intestinal and hepatic expression of BNIP3 in necrotizing enterocolitis:
      regulation by nitric oxide and peroxynitrite.
AB  - Necrotizing enterocolitis (NEC) is characterized by the upregulation of
      proinflammatory proteins, nitrosative stress, and increased enterocyte apoptosis.
      We examined the expression and regulation of the Bcl-2/adenovirus EIB 19-kDa
      interacting protein 3 (BNIP3), a pro-apoptotic gene regulated by nitric oxide
      (NO) in hepatocytes, in NEC. Newborn rats subjected to hypoxia and fed a
      conventional formula by gavage (FFH) developed NEC and demonstrated elevated
      expression of BNIP3 mRNA and protein in mucosal scrapings of the ileal samples
      and in the liver. In contrast, control rats [breast-fed (BF) without hypoxia] did
      not develop NEC or elevated BNIP3 expression in these tissues. BNIP3 expression
      paralleled the histological manifestation of NEC. Supplementation of the formula
      with L-Nomega-(1-iminoethyl)lysine, an inducible NO synthase inhibitor, reduced
      BNIP3 expression in FFH animals to the levels found in BF animals. Both hypoxia
      and peroxynitrite upregulated BNIP3 protein expression in human intestinal cells.
      Finally, ileal samples obtained from infants undergoing surgical resection for
      acute NEC demonstrated higher levels of BNIP3 protein. Because hypoxia and
      formation of reactive nitrogen species may promote gut barrier failure, we
      propose that upregulation of the cell death-related protein BNIP3 is one possible
      mechanism associated with enterocyte cell death observed in the intestine with
      NEC.

PMID- 16002568
TI  - Ikappa-B kinase-2 inhibitor blocks inflammation in human airway smooth muscle and
      a rat model of asthma.
AB  - RATIONALE: Nuclear factor (NF)-kappaB is a transcription factor known to regulate
      the expression of many inflammatory genes, including cytokines, chemokines, and
      adhesion molecules. NF-kappaB is held inactive in the cytoplasm, bound to I
      kappaB. The removal of I-kappaB, via the actions of inhibitor of kappaB (I
      kappaB) kinase-2 (IKK-2), allows NF-kappaB to enter the nucleus. OBJECTIVES: To
      determine the impact of inhibiting IKK-2 on in vitro and in vivo models of airway
      inflammation. METHODS: The effect of inhibiting IKK-2 was assessed in stimulated,
      cultured, primary human airway smooth muscle cells and an antigen-driven rat
      model of lung inflammation. MEASUREMENTS: The release of cytokines from cultured
      cells and inflammatory cytokine expression and cellular burden in the lung were
      determined. MAIN RESULTS: Two structurally distinct molecules and dominant
      negative technology demonstrated that inhibition of IKK-2 activity completely
      blocked cytokine release from cultured cells, whereas the two glucocorticoid
      comparators had limited impact on granulocyte colony-stimulating factor,
      interleukin 8, and eotaxin release. In addition, in an in vivo antigen-driven
      model of airway inflammation, the IKK-2 inhibitor blocked NF-kappaB nuclear
      translocation, which was associated with a reduction in inflammatory cytokine
      gene and protein expression, airway eosinophilia, and late asthmatic reaction,
      similar in magnitude to that obtained with budesonide. CONCLUSION: This study
      demonstrates that inhibiting IKK-2 results in a general reduction of the
      inflammatory response in vitro and in vivo. Compounds of this class could have
      therapeutic utility in the treatment of asthma and may, in certain respects,
      possess a beneficial efficacy profile compared with that of a steroid.

PMID- 16002569
TI  - A novel polymorphism in secretory phospholipase A2-IID is associated with body
      weight loss in chronic obstructive pulmonary disease.
AB  - RATIONALE: Chronic and systemic inflammation, a potential cause of body weight
      loss in patients with chronic obstructive pulmonary disease (COPD), may be
      associated with the proinflammatory properties of secretory phospholipases A2
      (sPLA2s), especially the group II subfamily sPLA2s. OBJECTIVES: We tested our
      hypothesis that the individual susceptibility to body weight loss in patients
      with COPD is attributed to the genetic variances of this sPLA2 gene region.
      METHODS: A total of 12 single nucleotide polymorphisms (SNPs) encompassing the
      sPLA2 gene region were determined in 276 male patients with COPD. MEASUREMENTS
      AND MAIN RESULTS: We first analyzed our patients whose body mass index (BMI) was
      at the bottom 100 (BMI, 17.13 +/- 1.29 kg/m2) and at the top 100 (23.83 +/- 1.98)
      in relation to SNPs. Both the Fisher's exact test (odds ratio, 2.36; 95%
      confidence interval, 1.34-4.18; p = 0.004) and logistic regression analysis (odds
      ratio, 2.10; 95% confidence interval, 1.13-3.90; p = 0.019) showed statistical
      significance between one SNP (National Center for Biotechnology Information SNP
      reference: rs584367) and the reduction of BMI in the recessive model in patients
      with COPD. Using all the patients, a significant difference between the values of
      BMI (log transformed) of the mutant group (CT + TT) and that of the nonmutant
      group (CC) of this SNP (mean [SE], 1.293 [0.005] vs. 1.317 [0.006]; p = 0.003)
      was found after adjustment for age, smoking habit, and pulmonary function
      (analysis of covariance). Importantly, this SNP caused a change in amino acids in
      sPLA2-IID protein (Gly80Ser). CONCLUSIONS: These results suggest that sPLA2-IID
      may be one of the susceptibility genes that contribute to body weight loss in
      patients with COPD.

PMID- 16002571
TI  - Bacteria and airway inflammation in chronic obstructive pulmonary disease: more
      evidence.

PMID- 16002570
TI  - Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary
      hypertension in rat lungs.
AB  - RATIONALE: In cigarette smoking-induced chronic obstructive pulmonary disease,
      structural and functional derangements are characterized by parenchymal
      destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl
      coenzyme-A reductase inhibitors that have been used as lipid-lowering agents.
      These drugs also have additional pharmacologic properties, including
      antiinflammation, scavenging reactive oxygen species, restoring endothelial
      function, and antithrombogenesis, all of which can counteract the harmful effects
      of cigarette smoking. OBJECTIVE: We performed assays to determine whether
      simvastatin could attenuate lung damage induced by chronic cigarette smoking in
      rats. METHODS: In Sprague-Dawley rats exposed to cigarette smoke for 16 weeks,
      morphologic changes in the lungs and pulmonary arterial pressure were examined.
      MAIN RESULTS: Simvastatin inhibited lung parenchymal destruction and development
      of pulmonary hypertension, and also inhibited peribronchial and perivascular
      infiltration of inflammatory cells and induction of matrix metalloproteinase-9
      activity in lung tissue. Simvastatin additionally prevented pulmonary vascular
      remodeling and the changes in endothelial nitric oxide synthase expression
      induced by smoking. In human lung microvascular endothelial cells, simvastatin
      increased expression of endothelial nitric oxide synthase mRNA. CONCLUSIONS:
      Simvastatin ameliorated the structural and functional derangements of the lungs
      caused by cigarette smoking, partly by suppressing inflammation and matrix
      metalloproteinase-9 induction and preventing pulmonary vascular abnormality.
      These findings indicate that statins may play a role in the treatment of
      cigarette smoking-induced chronic obstructive pulmonary disease.

PMID- 16002572
TI  - GOAL--asthma control, but at what cost?

PMID- 16002574
TI  - Consideration of important preanalytical conditions for the assessment of
      circulating matrix metalloproteinase-9.

PMID- 16002576
TI  - Penh is not a validated technique for measuring airway function in mice.

PMID- 16002577
TI  - Bone morphogenetic protein receptor type II C-terminus interacts with c-Src:
      implication for a role in pulmonary arterial hypertension.
AB  - Mutations of bone morphogenetic protein receptor type II (BMPR-II) have been
      associated with familial and idiopathic pulmonary arterial hypertension (PAH).
      BMPR-II is a member of the transforming growth factor-beta receptor superfamily.
      It consists of extracellular, transmembrane, and kinase domains, and a unique C
      terminus with mostly unknown function. However, a number of PAH-causing mutations
      are predicted to truncate the C-terminus, suggesting that this domain plays an
      important role in the homeostasis of pulmonary vessels. In this study, we sought
      to elucidate the functional role of this C-terminus by seeking its interacting
      partners. Using yeast two-hybrid screening, we identified c-Src tyrosine kinase
      as a binding partner of this C-terminus. In vitro co-immunoprecipitation
      confirmed their interaction. Mutations truncating the C-terminus disrupted their
      interaction, while missense mutation within kinase domain reduced their
      interaction. In addition, BMPR-II and c-Src tyrosine kinase colocalized within
      intracellular aggregates when overexpressed in HEK293 cells. Moreover, mutations
      truncating the C-terminus disrupted their colocalization, whereas missense
      mutation within kinase domain had no effect on their colocalization. Furthermore,
      BMP ligand stimulation decreased c-Src-activating phosphorylation at Tyrosine 418
      in pulmonary smooth muscle cells in both time- and concentration-dependent
      manners. Mutations that truncated the C-terminus abolished this response. Taken
      together, these results suggest a model in which proliferative effect of c-Src by
      vasoactive molecules is balanced by opposing effect of BMP signaling in basal
      state, and the loss of this balance due to BMPR2 mutations leads to increased c
      Src activity and subsequently cell growth.

PMID- 16002578
TI  - Heterotrimeric G proteins and the platelet-derived growth factor receptor-beta
      contribute to hypoxic proliferation of smooth muscle cells.
AB  - Hypoxic proliferation of pulmonary arterial smooth muscle cells (PASMC) is
      mitogen dependent, but the signaling pathways mediating hypoxia-induced cell
      growth are not well understood. We investigated hypoxic proliferation in primary
      cultures from porcine pulmonary artery smooth muscle. The cells were grown in
      medium with or without platelet-derived growth factor (PDGF)-B, a potent smooth
      muscle cell mitogen. Hypoxia induced upregulation of PDGF receptor-beta
      expression, the primary receptor for PDGF-B. However, PDGF-B-mediated hypoxic
      enhancement of proliferation was abolished by pertussis toxin, indicating (1)
      involvement of heterotrimeric Galpha i proteins and (2) minimal effect of
      increased PDGF receptor expression in hypoxic enhancement of proliferation. We
      treated PASMC with labeled, nonhydrolyzable analogs of GTP to determine directly
      if GTP binding proteins were activated by hypoxia in PASMC. We show that hypoxia
      stimulates GTP incorporation in PASMC both in the presence and absence of PDGF-B.
      Serum-starved PASMC are able to increase their incorporation of GTP after only 10
      min of hypoxia, and this response is not pertussis toxin sensitive. In serum
      starved PASMC, we show that hypoxia stimulates incorporation of GTP into a 44-kD
      protein. The results show that heterotrimeric G proteins are involved in hypoxia
      induced signaling in pulmonary vascular smooth muscle cells.

PMID- 16002579
TI  - Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
AB  - Voltage-dependent ion channels contain voltage sensors that allow them to switch
      between nonconductive and conductive states over the narrow range of a few
      hundredths of a volt. We investigated the mechanism by which these channels sense
      cell membrane voltage by determining the x-ray crystal structure of a mammalian
      Shaker family potassium ion (K+) channel. The voltage-dependent K+ channel Kv1.2
      grew three-dimensional crystals, with an internal arrangement that left the
      voltage sensors in an apparently native conformation, allowing us to reach three
      important conclusions. First, the voltage sensors are essentially independent
      domains inside the membrane. Second, they perform mechanical work on the pore
      through the S4-S5 linker helices, which are positioned to constrict or dilate the
      S6 inner helices of the pore. Third, in the open conformation, two of the four
      conserved Arg residues on S4 are on a lipid-facing surface and two are buried in
      the voltage sensor. The structure offers a simple picture of how membrane voltage
      influences the open probability of the channel.

PMID- 16002582
TI  - Redefining science.

PMID- 16002581
TI  - Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
AB  - Voltage-dependent potassium ion (K+) channels (Kv channels) conduct K+ ions
      across the cell membrane in response to changes in the membrane voltage, thereby
      regulating neuronal excitability by modulating the shape and frequency of action
      potentials. Here we report the crystal structure, at a resolution of 2.9
      angstroms, of a mammalian Kv channel, Kv1.2, which is a member of the Shaker K+
      channel family. This structure is in complex with an oxido-reductase beta subunit
      of the kind that can regulate mammalian Kv channels in their native cell
      environment. The activation gate of the pore is open. Large side portals
      communicate between the pore and the cytoplasm. Electrostatic properties of the
      side portals and positions of the T1 domain and beta subunit are consistent with
      electrophysiological studies of inactivation gating and with the possibility of
      K+ channel regulation by the beta subunit.

PMID- 16002580
TI  - Discovery of very high energy gamma rays associated with an x-ray binary.
AB  - X-ray binaries are composed of a normal star in orbit around a neutron star or
      stellar-mass black hole. Radio and x-ray observations have led to the presumption
      that some x-ray binaries called microquasars behave as scaled-down active
      galactic nuclei. Microquasars have resolved radio emission that is thought to
      arise from a relativistic outflow akin to active galactic nuclei jets, in which
      particles can be accelerated to large energies. Very high energy gamma-rays
      produced by the interactions of these particles have been observed from several
      active galactic nuclei. Using the High Energy Stereoscopic System, we find
      evidence for gamma-ray emission of >100 gigaelectron volts from a candidate
      microquasar, LS 5039, showing that particles are also accelerated to very high
      energies in these systems.

PMID- 16002583
TI  - Planetary science. Deep Impact makes a lasting impression on comet Tempel 1.

PMID- 16002584
TI  - Scientific publishing. Britain's research agencies endorse public access.

PMID- 16002585
TI  - Anthropology. A new skirmish in the Yanomamo wars.

PMID- 16002586
TI  - Spanish science. Madrid heart center to be rescued.

PMID- 16002587
TI  - Structural biology. Ten centers chosen to decode protein structures.

PMID- 16002588
TI  - Biosecurity. New panel to offer guidance on dual-use science.

PMID- 16002589
TI  - Avian influenza. Potentially more lethal variant hits migratory birds in China.

PMID- 16002590
TI  - Research management. Scientists say Genome Canada's cofunding rules stymie good
      ideas.

PMID- 16002591
TI  - Pesticide testing. EPA draft rules for human subjects draw fire.

PMID- 16002592
TI  - Epidemiology. Radiation dangerous even at lowest doses.

PMID- 16002593
TI  - Evolutionary genetics. Are humans still evolving?

PMID- 16002594
TI  - Quantum computing. Teaching qubits new tricks.

PMID- 16002595
TI  - Education. Biologist helps students get a leg up on scientific inquiry.

PMID- 16002596
TI  - Stem cells. Embryo-free techniques gain momentum.

PMID- 16002597
TI  - Stem cells. California institute: most systems go.

PMID- 16002598
TI  - When the world is not your oyster.

PMID- 16002599
TI  - Regulating mercury: what's at stake?

PMID- 16002600
TI  - The long search for black holes.

PMID- 16002601
TI  - Encouraging discovery and innovation.

PMID- 16002602
TI  - Keeping medical research ethical.

PMID- 16002603
TI  - Economics. Individual accounts: lessons from international experience.

PMID- 16002604
TI  - Immunology. Now presenting: gammadelta T cells.

PMID- 16002605
TI  - Materials science. Hierarchies in biomineral structures.

PMID- 16002606
TI  - Ocean science. Warming the world's oceans.

PMID- 16002607
TI  - Anthropology. The remaking of Australia's ecology.

PMID- 16002608
TI  - Complexity in strongly correlated electronic systems.
AB  - A wide variety of experimental results and theoretical investigations in recent
      years have convincingly demonstrated that several transition metal oxides and
      other materials have dominant states that are not spatially homogeneous. This
      occurs in cases in which several physical interactions-spin, charge, lattice,
      and/or orbital-are simultaneously active. This phenomenon causes interesting
      effects, such as colossal magnetoresistance, and it also appears crucial to
      understand the high-temperature superconductors. The spontaneous emergence of
      electronic nanometer-scale structures in transition metal oxides, and the
      existence of many competing states, are properties often associated with complex
      matter where nonlinearities dominate, such as soft materials and biological
      systems. This electronic complexity could have potential consequences for
      applications of correlated electronic materials, because not only charge
      (semiconducting electronic), or charge and spin (spintronics) are of relevance,
      but in addition the lattice and orbital degrees of freedom are active, leading to
      giant responses to small perturbations. Moreover, several metallic and insulating
      phases compete, increasing the potential for novel behavior.

PMID- 16002609
TI  - Bioluminescent and red-fluorescent lures in a deep-sea siphonophore.
AB  - Bioluminescence (light production) and fluorescence (re-emission of absorbed
      radiation as light) are found in an unaccountably diverse array of marine
      organisms, where their functions are largely unknown. Here we report a deep-sea
      siphonophore that twitches glowing lures to attract fish. This is rare evidence
      of bioluminescence used for prey attraction among nonvisual marine organisms. The
      lures also contain red fluorescent material that shifts the wavelength of emitted
      light. The existence of a red-luminescent invertebrate suggests that long
      wavelength light plays a greater role in marine interactions than previously
      suspected.

PMID- 16002610
TI  - Single-electron delocalization in hybrid vertical-lateral double quantum dots.
AB  - We used a hybrid vertical-lateral double-dot device, consisting of laterally
      coupled vertical quantum dots, to measure the interdot tunnel coupling. By using
      nonlinear transport measurements of "Coulomb diamonds," we showed that an
      inherent asymmetry in the capacitances of the component dots influences the
      diamond slopes, thereby allowing for the determination of the dot through which
      the electron has passed. We used this technique to prepare a delocalized one
      electron state and Heitler-London (HL) two-electron state, and we showed that the
      interdot tunnel coupling, which determines whether HL is the ground state, is
      tunable. This implies that our device may be useful for implementing two-electron
      spin entanglement.

PMID- 16002611
TI  - Tunable supercurrent through semiconductor nanowires.
AB  - Nanoscale superconductor/semiconductor hybrid devices are assembled from indium
      arsenide semiconductor nanowires individually contacted by aluminum-based
      superconductor electrodes. Below 1 kelvin, the high transparency of the contacts
      gives rise to proximity-induced superconductivity. The nanowires form
      superconducting weak links operating as mesoscopic Josephson junctions with
      electrically tunable coupling. The supercurrent can be switched on/off by a gate
      voltage acting on the electron density in the nanowire. A variation in gate
      voltage induces universal fluctuations in the normal-state conductance, which are
      clearly correlated to critical current fluctuations. The alternating-current
      Josephson effect gives rise to Shapiro steps in the voltage-current
      characteristic under microwave irradiation.

PMID- 16002612
TI  - Skeleton of Euplectella sp.: structural hierarchy from the nanoscale to the
      macroscale.
AB  - Structural materials in nature exhibit remarkable designs with building blocks,
      often hierarchically arranged from the nanometer to the macroscopic length
      scales. We report on the structural properties of biosilica observed in the
      hexactinellid sponge Euplectella sp. Consolidated, nanometer-scaled silica
      spheres are arranged in well-defined microscopic concentric rings glued together
      by organic matrix to form laminated spicules. The assembly of these spicules into
      bundles, effected by the laminated silica-based cement, results in the formation
      of a macroscopic cylindrical square-lattice cagelike structure reinforced by
      diagonal ridges. The ensuing design overcomes the brittleness of its constituent
      material, glass, and shows outstanding mechanical rigidity and stability. The
      mechanical benefits of each of seven identified hierarchical levels and their
      comparison with common mechanical engineering strategies are discussed.

PMID- 16002613
TI  - Isolation of two seven-membered ring C58 fullerene derivatives: C58F17CF3 and
      C58F18.
AB  - Fluorination of C60 at 550 degrees C leads to milligram quantities of two stable
      fullerene derivatives with 58-carbon cage structures: C58F18 and C58F17CF3. The
      compounds were characterized by mass spectrometry and fluorine nuclear magnetic
      resonance spectroscopy, and the data support a heptagonal ring in the framework.
      The resulting strain, which has hindered past attempts to prepare these smaller
      quasi-fullerenes, is mitigated here by hybridization change of some of the
      carbons in the pentagons from sp2 to sp3 because of fluorine addition. The loss
      of carbon from C60 is believed to occur via sequential fluorine addition to a CC
      single bond and an adjacent CC bond, followed by loss of a:CF2 carbene.

PMID- 16002614
TI  - Resonating valence-bond ground state in a phenalenyl-based neutral radical
      conductor.
AB  - An organic material composed of neutral free radicals based on the
      spirobiphenalenyl system exhibits a room temperature conductivity of 0.3 siemens
      per centimeter and a high-symmetry crystal structure. It displays the temperature
      independent Pauli paramagnetism characteristic of a metal with a magnetic
      susceptibility that implies a density of states at the Fermi level of 15.5 states
      per electron volt per mole. Extended Huckel calculations indicate that the solid
      is a three-dimensional organic metal with a band width of approximately 0.5
      electron volts. However, the compound shows activated conductivity (activation
      energy, 0.054 electron volts) and an optical energy gap of 0.34 electron volts.
      We argue that these apparently contradictory properties are best resolved in
      terms of the resonating valence-bond ground state originally suggested by
      Pauling, but with the modifications introduced by Anderson.

PMID- 16002615
TI  - Ecosystem collapse in Pleistocene Australia and a human role in megafaunal
      extinction.
AB  - Most of Australia's largest mammals became extinct 50,000 to 45,000 years ago,
      shortly after humans colonized the continent. Without exceptional climate change
      at that time, a human cause is inferred, but a mechanism remains elusive. A
      140,000-year record of dietary delta(13)C documents a permanent reduction in food
      sources available to the Australian emu, beginning about the time of human
      colonization; a change replicated at three widely separated sites and in the
      marsupial wombat. We speculate that human firing of landscapes rapidly converted
      a drought-adapted mosaic of trees, shrubs, and nutritious grasslands to the
      modern fire-adapted desert scrub. Animals that could adapt survived; those that
      could not, became extinct.

PMID- 16002616
TI  - Stomatal patterning and differentiation by synergistic interactions of receptor
      kinases.
AB  - Coordinated spacing and patterning of stomata allow efficient gas exchange
      between plants and the atmosphere. Here we report that three ERECTA (ER)-family
      leucine-rich repeat-receptor-like kinases (LRR-RLKs) together control stomatal
      patterning, with specific family members regulating the specification of stomatal
      stem cell fate and the differentiation of guard cells. Loss-of-function mutations
      in all three ER-family genes cause stomatal clustering. Genetic interactions with
      a known stomatal patterning mutant too many mouths (tmm) revealed stoichiometric
      epistasis and combination-specific neomorphism. Our findings suggest that the
      negative regulation of ER-family RLKs by TMM, which is an LRR receptor-like
      protein, is critical for proper stomatal differentiation.

PMID- 16002617
TI  - FKF1 F-box protein mediates cyclic degradation of a repressor of CONSTANS in
      Arabidopsis.
AB  - The temporal control of CONSTANS (CO) expression and activity is a key mechanism
      in photoperiodic flowering in Arabidopsis. FLAVIN-BINDING, KELCH REPEAT, F-BOX 1
      (FKF1) protein regulates CO transcription, although the molecular mechanism is
      unknown. We demonstrate here that FKF1 controls the stability of a Dof
      transcription factor, CYCLING DOF FACTOR 1 (CDF1). FKF1 physically interacts with
      CDF1, and CDF1 protein is more stable in fkf1 mutants. Plants with elevated
      levels of CDF1 flower late and have reduced expression of CO. CDF1 and CO are
      expressed in the same tissues, and CDF1 binds to the CO promoter. Thus, FKF1
      controls daily CO expression in part by degrading CDF1, a repressor of CO
      transcription.

PMID- 16002618
TI  - The kinesin Klp2 mediates polarization of interphase microtubules in fission
      yeast.
AB  - Fission yeast (Schizosaccharomyces pombe) cells grow longitudinally in a manner
      dependent on a polarized distribution of their interphase microtubules. We found
      that this distribution required sliding of microtubules toward the cell center
      along preexisting microtubules. This sliding was mediated by the minus end
      directed kinesin motor Klp2, which helped microtubules to become properly
      organized with plus ends predominantly oriented toward the cell ends and minus
      ends toward the cell center. Thus, interphase microtubules in the fission yeast
      require motor activities for their proper organization.

PMID- 16002619
TI  - A self-organized vortex array of hydrodynamically entrained sperm cells.
AB  - Many patterns in biological systems depend on the exchange of chemical signals
      between cells. We report a spatiotemporal pattern mediated by hydrodynamic
      interactions. At planar surfaces, spermatozoa self-organized into dynamic
      vortices resembling quantized rotating waves. These vortices formed an array with
      local hexagonal order. Introducing an order parameter that quantifies
      cooperativity, we found that the array appeared only above a critical sperm
      density. Using a model, we estimated the hydrodynamic interaction force between
      spermatozoa to be approximately 0.03 piconewtons. Thus, large-scale coordination
      of cells can be regulated hydrodynamically, and chemical signals are not
      required.

PMID- 16002620
TI  - Inferential structure determination.
AB  - Macromolecular structures calculated from nuclear magnetic resonance data are not
      fully determined by experimental data but depend on subjective choices in data
      treatment and parameter settings. This makes it difficult to objectively judge
      the precision of the structures. We used Bayesian inference to derive a
      probability distribution that represents the unknown structure and its precision.
      This probability distribution also determines additional unknowns, such as theory
      parameters, that previously had to be chosen empirically. We implemented this
      approach by using Markov chain Monte Carlo techniques. Our method provides an
      objective figure of merit and improves structural quality.

PMID- 16002621
TI  - Crossmodal interactions between olfactory and visual learning in Drosophila.
AB  - Different modalities of sensation interact in a synergistic or antagonistic
      manner during sensory perception, but whether there is also interaction during
      memory acquisition is largely unknown. In Drosophila reinforcement learning, we
      found that conditioning with concurrent visual and olfactory cues reduced the
      threshold for unimodal memory retrieval. Furthermore, bimodal preconditioning
      followed by unimodal conditioning with either a visual or olfactory cue led to
      crossmodal memory transfer. Crossmodal memory acquisition in Drosophila may
      contribute significantly to learning in a natural environment.

PMID- 16002622
TI  - Bone marrow stromal cells generate muscle cells and repair muscle degeneration.
AB  - Bone marrow stromal cells (MSCs) have great potential as therapeutic agents. We
      report a method for inducing skeletal muscle lineage cells from human and rat
      general adherent MSCs with an efficiency of 89%. Induced cells differentiated
      into muscle fibers upon transplantation into degenerated muscles of rats and mdx
      nude mice. The induced population contained Pax7-positive cells that contributed
      to subsequent regeneration of muscle upon repetitive damage without additional
      transplantation of cells. These MSCs represent a more ready supply of myogenic
      cells than do the rare myogenic stem cells normally found in muscle and bone
      marrow.

PMID- 16002624
TI  - Why FRET? Focus on "beta-Adrenergic and muscarinic receptor-induced changes in
      cAMP activity in adult cardiac myocytes using a FRET-based biosensor".

PMID- 16002625
TI  - Osteogenic differentiation is inhibited and angiogenic expression is enhanced in
      MC3T3-E1 cells cultured on three-dimensional scaffolds.
AB  - Osteogenic differentiation of osteoprogenitor cells in three-dimensional (3D) in
      vitro culture remains poorly understood. Using quantitative real-time RT-PCR
      techniques, we examined mRNA expression of alkaline phosphatase, osteocalcin, and
      vascular endothelial growth factor (VEGF) in murine preosteoblastic MC3T3-E1
      cells cultured for 48 h and 14 days on conventional two-dimensional (2D) poly(l
      lactide-co-glycolide) (PLGA) films and 3D PLGA scaffolds. Differences in VEGF
      secretion and function between 2D and 3D culture systems were examined using
      Western blots and an in vitro Matrigel-based angiogenesis assay. Expression of
      both alkaline phosphatase and osteocalcin in cells cultured on 3D scaffolds was
      significantly downregulated relative to 2D controls in 48 h and 14 day cultures.
      In contrast, elevated levels of VEGF expression in 3D culture were noted at every
      time point in short- and long-term culture. VEGF protein secretion in 3D cultures
      was triple the amount of secretion observed in 2D controls. Conditioned medium
      from 3D cultures induced an enhanced level of angiogenic activity, as evidenced
      by increases in branch points observed in in vitro angiogenesis assays. These
      results collectively indicate that MC3T3-E1 cells commit to osteogenic
      differentiation at a slower rate when cultured on 3D PLGA scaffolds and that VEGF
      is preferentially expressed by these cells when they are cultured in three
      dimensions.

PMID- 16002623
TI  - Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals.
AB  - The study of muscle physiology has undergone many changes over the past 25 years
      and has moved from purely physiological studies to those intimately intertwined
      with molecular and cell biological questions. To ask these questions, it is
      necessary to be able to transfer genetic reagents to cells both in culture and,
      ultimately, in living animals. Over the past 10 years, a number of different
      chemical and physical approaches have been developed to transfect living
      skeletal, smooth, and cardiac muscle systems with varying success and efficiency.
      This review provides a survey of these methods and describes some more recent
      developments in the field of in vivo gene transfer to these various muscle types.
      Both gene delivery for overexpression of desired gene products and delivery of
      nucleic acids for downregulation of specific genes and their products are
      discussed to aid the physiologist, cell biologist, and molecular biologist in
      their studies on whole animal biology.

PMID- 16002626
TI  - Use of Peptide library screening to detect a previously unknown linear diagnostic
      epitope: proof of principle by use of lyme disease sera.
AB  - Diagnostic peptides previously isolated from phage-displayed libraries by
      affinity selection with serum antibodies from patients with Lyme disease were
      found to give reproducible serum reactivity patterns when tested in two different
      enzyme-linked immunosorbent assay formats. In addition, the hypothetical
      possibility that peptides selected by this type of "epitope discovery" technique
      might identify the original antigens eliciting antibody responses was tested by
      searching for sequence similarities in bacterial protein databases. In support of
      this hypothesis, our search uncovered similarities between peptides representing
      two different sequence motifs and sequences in the VlsE and BBA61 antigens of
      Borrelia burgdorferi. Utilizing synthetic peptides, we verified that the sequence
      KAASKETPPALNK, located at the C terminus of the VlsE antigen, had the same
      reactivity pattern to sera from patients with extracutaneous Lyme disease as the
      diagnostic peptide SKEKPPSLNWPA, with which it shared a 7-amino-acid-residue
      match (consensus residues are underlined). A peptide with conservative mutations
      of five of the consensus residues was nonreactive, strongly suggesting that the
      VlsE sequence represents the epitope that originally elicited antibody responses
      in these patients. The diagnostic sensitivity of this new VlsE epitope was
      relatively low (30%) compared to that (100%) of the well-documented C6 diagnostic
      peptide of VlsE when tested in our small cohort of 10 patients with Lyme disease.
      Nonetheless, the identification of this previously unknown epitope serves as a
      proof of the principle of the hypothetical ability of "epitope discovery"
      techniques to detect specific microbial antigens with diagnostic relevance in
      infectious diseases.

PMID- 16002628
TI  - Bov-tA short interspersed nucleotide element sequences in circulating nucleic
      acids from sera of cattle with bovine spongiform encephalopathy (BSE) and sera of
      cattle exposed to BSE.
AB  - Circulating nucleic acids (CNA) are known to be enriched in repetitive DNA
      sequences in humans. Here, bovine sera CNA were analyzed to determine if cell
      stress-related short interspersed nucleotide elements (SINEs) could be detected
      in sera from cattle associated with bovine spongiform encephalopathy (BSE).
      Nucleic acids were extracted, amplified, cloned, and sequenced from the sera of
      protease-resistant prion protein (PrP(res))-positive cattle (n = 2) and sera from
      BSE-cohort cows (n = 6); 150 out of 163 clones revealed the presence of, on
      average, an 80-bp sequence from the 3' region of Bov-tA SINE. A PCR protocol was
      developed that differentially identified SINE-associated CNA in BSE-exposed
      versus normal cattle. CNA were extracted from a serum vesicular fraction after
      controlled blood collection and processing procedures. Sera from four confirmed
      cases of BSE, 137 BSE-exposed cohort animals associated with eight confirmed BSE
      cases, and 845 healthy, PrP(res)-negative control cows were tested. All four sera
      from confirmed BSE cases were repeatedly reactive in the assay. BSE-exposed
      cohorts had a 100-fold higher occurrence of repeatedly reactive individuals per
      cohort (average = 63%; range = 33% to 91%), compared to healthy controls (average
      = 0.6%; P < 0.001). This study shows that BSE-confirmed and cohort animals
      possess a unique profile of SINE-associated serum CNA that can be utilized as a
      marker that highly correlates to BSE exposure.

PMID- 16002627
TI  - Effect of malnutrition on K+ current in T lymphocytes.
AB  - Severe malnutrition in children is frequently associated with infectious
      diseases. Animal models have been useful for studying the effects of
      malnutrition. One of the immunosuppressive mechanisms of malnutrition is
      inhibition of the activation of T lymphocytes. The voltage-dependent K(V)
      potassium channels are vital for the activation of T lymphocytes. The blockade of
      K(V) channels inhibits the activation of T lymphocytes. Malnutrition could affect
      the suitable synthesis of K(V) channels in T lymphocytes, producing changes in
      the magnitude and/or dependency of the voltage of the K+ current. We reported a
      significant decrease in the K+ current and activation to a 20 mV more positive
      membrane potential in T lymphocytes of rats with severe malnutrition. These
      results indicate that the diminution in the K+ conductance by alteration of K(V)
      channels in severe malnutrition is one of the mechanisms that inhibit the
      activation of T lymphocytes.

PMID- 16002629
TI  - Multiplexed particle-based anti-granulocyte macrophage colony stimulating factor
      assay used as pulmonary diagnostic test.
AB  - Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of
      lipoproteinaceous material within the lung alveoli. Recent studies indicate that
      PAP is an autoimmune disease characterized by a neutralizing anti-granulocyte
      macrophage colony stimulating factor (GM-CSF) antibody. At present the only
      definitive diagnostic test for PAP is open lung biopsy. We have previously
      published that anti-GM-CSF is diagnostic for PAP and correlates with disease
      pathogenesis using a traditional serial anti-GM-CSF antibody titer format (T. L.
      Bonfield, M. S. Kavuru, and M. J. Thomassen, Clin. Immunol. 105:342-350, 2002).
      Titer analysis is a semiquantitative method, and often subtle changes in antibody
      titer are not detectable. In this report we present data to support anti-GM-CSF
      detection by a quantitative highly sensitive multiplexed particle-based assay
      which has the potential to be a clinical diagnostic test.

PMID- 16002631
TI  - Multivalent group A streptococcal vaccine elicits bactericidal antibodies against
      variant M subtypes.
AB  - Group A streptococci cause a wide spectrum of clinical illness. One of several
      strategies for vaccine prevention of these infections is based on the type
      specific M protein epitopes. A multivalent M protein-based vaccine containing
      type-specific determinants from 26 different M serotypes is now in clinical
      trials. Recent epidemiologic studies have shown that, within some serotypes, the
      amino-terminal M protein sequence may show natural variation, giving rise to
      subtypes. This raises the possibility that vaccine-induced antibodies against the
      parent type may not be as effective in promoting bactericidal killing of variant
      subtypes. In the present study we used rabbit antisera against the 26-valent M
      protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci,
      which were represented by multiple subtypes. We show that the vaccine antibodies
      effectively promoted in vitro bactericidal activity despite the fact that the M
      proteins contained naturally occurring variant sequences in the regions
      corresponding to the vaccine sequence. Our results show that the variant M
      proteins generally do not result in significant differences in opsonization
      promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that
      a multivalent M protein vaccine may not permit variant subtypes of group A
      streptococci to escape in a highly immunized population.

PMID- 16002630
TI  - Clinical and immunological features of 65 Iranian patients with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency disease
      characterized by hypogammaglobulinemia and recurrent bacterial infections. The
      records of 65 patients with CVID (37 males and 28 females) in the age range of 24
      to 537 months were reviewed. By the year 2003, 11 patients had died and seven
      patients could not be located. The total follow-up period was 221 patient-years.
      The median diagnostic delay (time between onset and diagnosis) in our patient
      group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin
      G (IgG), IgM, and IgA levels were below the level normal for the patients' age;
      the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the
      patients presented with infectious diseases at the time of onset, the most common
      of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and
      recurrent infections were also found in almost all of the patients, particularly
      involving respiratory and gastrointestinal systems. The most common infections,
      before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute
      sinusitis, and otitis media. CVID should be considered in any patient with a
      history of recurrent infections and decreased levels of all serum immunoglobulin
      isotypes.

PMID- 16002632
TI  - Proteomic but not enzyme-linked immunosorbent assay technology detects amniotic
      fluid monomeric calgranulins from their complexed calprotectin form.
AB  - Four proteomic biomarkers (human neutrophil peptide 1 [HNP1], HNP2 [defensins],
      calgranulin C [Cal-C], and Cal-A) characterize the fingerprint of intra-amniotic
      inflammation (IAI). We compared proteomic technology using surfaced-enhanced
      laser desorption-ionization-time of flight (SELDI-TOF) mass spectrometry to
      enzyme-linked immunosorbent assay (ELISA) for detection of these biomarkers.
      Amniocentesis was performed on 48 women enrolled in two groups: those with intact
      membranes (n = 27; gestational age [GA], 26.0 +/- 0.8 weeks) and those with
      preterm premature rupture of the membranes (PPROM; n = 21; GA, 28.4 +/- 0.9
      weeks). Paired abdominal amniotic fluids (aAFs)-vaginal AFs (vAFs) were analyzed
      in PPROM women. Quantitative aspects of HNP1-3, Cal-C, Cal-A, and calprotectin (a
      complex of Cal-A with Cal-B) were assessed by ELISA. SELDI-TOF mass spectrometry
      tracings from 16/48 (33.3%) aAFs and 13/17 (88.2%) vAFs were consistent with IAI
      (three or four biomarkers present). IAI (by SELDI-TOF mass spectrometry) was
      associated with increased HNP1-3 and Cal-C measured by ELISA. However,
      immunoassays detected Cal-A in only 4 of the AFs even though its specific SELDI
      TOF mass spectrometry peak was identified in 19/48 AFs. Calprotectin
      immunoreactivity was decreased in AFs retrieved from women with IAI (P = 0.01).
      In conclusion, IAI is associated with increased HNP1-3 levels. In the absence of
      isoform-specific ELISAs, mass spectrometry remains the only way to discriminate
      the HNP biomarker isoforms. Monomeric Cal-A is not reliably estimated by specific
      ELISA as it binds to Cal-B to form the calprotectin complex. Cal-C was reliably
      measured by SELDI-TOF mass spectrometry or specific ELISA.

PMID- 16002633
TI  - Immunoglobulin G subclass profile of antimeasles response in vaccinated children
      and in adults with measles history.
AB  - The aim of this study was to investigate measles-specific immunoglobulin G (IgG)
      subclass profile in vaccinated children and in adults with natural infection.
      Serum samples were collected before and 30 days after vaccination. The sera from
      51 late convalescent adults and seven adults with natural measles infection at
      the 12th day after onset of rash have been also investigated. Measles IgG
      antibodies and specific IgG subclasses were tested by enzyme-linked immunosorbent
      techniques. In children younger than 3 years, the predominant subclass was IgG3,
      which contributed, on average, 63.3% of the total IgG response. The contributions
      of specific IgG1 and IgG4 to the total IgG antimeasles response were lower (19.9%
      and 16.8%, respectively), whereas IgG2 was not found. In contrast, in the group
      of children older than 4 years, just IgG2 was a predominant subclass; it
      contributed 42.6% of the total IgG response. Other subclasses were also present
      but the contribution was much lower. In adult volunteers with measles history,
      IgG2 was a predominant subclass of total IgG. Thus, in early convalescence IgG2
      contributed 62% of the total IgG response, whereas in late convalescence the
      contribution was lower (41.4%). There were no visible differences in IgG subclass
      composition between subjects with natural infection and vaccinated children
      except those below 3 years of age. The humoral immune response of such subjects
      is immature and the IgG2 subclass of virus-specific antibodies has not been
      revealed in the sera.

PMID- 16002634
TI  - Evaluation of inapparent nosocomial severe acute respiratory syndrome coronavirus
      infection in Vietnam by use of highly specific recombinant truncated nucleocapsid
      protein-based enzyme-linked immunosorbent assay.
AB  - Severe acute respiratory syndrome (SARS) is a recently emerged human disease
      associated with pneumonia. Inapparent infection with SARS coronavirus (CoV) is
      not well characterized. To develop a safe, simple, and reliable screening method
      for SARS diagnosis and epidemiological study, two recombinant SARS-CoV
      nucleocapsid proteins (N' protein and (N)Delta(121) protein) were expressed in
      Escherichia coli, purified by affinity chromatography, and used as antigens for
      indirect, immunoglobulin G enzyme-linked immunosorbent assays (ELISA). Serum
      samples collected from healthy volunteers and SARS patients in Vietnam were used
      to evaluate the newly developed methods. The N' protein-based ELISA showed a
      highly nonspecific reaction. The (N)Delta(121) protein-based ELISA, with a
      nonspecific reaction drastically reduced compared to that of the nearly-whole
      length N' protein-based ELISA, resulted in higher rates of positive reactions,
      higher titers, and earlier detection than the SARS-CoV-infected cell lysate-based
      ELISA. These results indicate that our newly developed SARS-CoV (N)Delta(121)
      protein-based ELISA is not only safe but also a more specific and more sensitive
      method to diagnose SARS-CoV infection and hence a useful tool for large-scale
      epidemiological studies. To identify inapparent SARS-CoV infections, serum
      samples collected from health care workers (HCWs) in Vietnam were screened by the
      (N)Delta(121) protein-based ELISA, and positive samples were confirmed by a virus
      neutralization test. Four out of 149 HCWs were identified to have inapparent SARS
      CoV infection in Vietnam, indicating that subclinical SARS-CoV infection in
      Vietnam is rare but does exist.

PMID- 16002635
TI  - Evaluation of rapid prenatal human immunodeficiency virus testing in rural
      cameroon.
AB  - Pregnant women (n = 859) in rural Cameroonian prenatal clinics were screened by
      two rapid human immunodeficiency virus (HIV) antibody tests (rapid tests [RT])
      (Determine and Hema-Strip) using either whole blood or plasma. One additional RT
      (Capillus, HIV-CHEK, or Sero-Card) was used to resolve discordant results. RT
      results were compared with HIV-1 enzyme immunoassay (EIA) and Western blot (WB)
      results of matched dried blood spots (DBS) to assess the accuracy of HIV RTs. DBS
      EIA/WB identified 83 HIV antibody-reactive, 763 HIV antibody-nonreactive, and 13
      indeterminate specimens. RT results were evaluated in serial (two consecutive
      tests) or parallel (two simultaneous tests) testing algorithms. A serial
      algorithm using Determine and Hema-Strip yielded sensitivity and specificity
      results of 97.6% and 99.7%, respectively, whereas a parallel RT algorithm using
      Determine plus a second RT produced a sensitivity and specificity of 100% and
      99.7%, respectively. HIV RTs provide excellent alternatives for identifying HIV
      infection, and their field performance could be monitored using DBS testing
      strategies.

PMID- 16002636
TI  - polyethylene glycol-conjugated adenosine deaminase (ADA) therapy provides
      temporary immune reconstitution to a child with delayed-onset ADA deficiency.
AB  - We describe the effects of polyethylene glycol-conjugated adenosine deaminase
      (ADA) replacement therapy on lymphocyte counts, activation, apoptosis,
      proliferation, and cytokine secretion in a 14-month-old girl with "delayed-onset"
      ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected
      T cells (CD4, 150/microl; CD8, 459/microl), B cells (16/microl), and NK cells
      (55/microl). T cells were uniformly activated and largely apoptotic (CD4, 59%;
      CD8, 82%); and T-cell-dependent cytokine levels in plasma were elevated,
      including the levels of interleukin 2 (IL-2; 26 pg/ml), IL-4 (81 pg/ml), IL-5 (46
      pg/ml), gamma interferon (1,430 pg/ml), tumor necrosis factor alpha (210 pg/ml),
      and IL-10 (168 pg/ml). Mitogen-stimulated peripheral blood mononuclear cells show
      reduced IL-2 secretion and proliferation. During the first 5 months of therapy
      there was clinical improvement and partial immune reconstitution, with nearly
      normal lymphocyte subset numbers, reduced T-cell activation and CD4-cell
      apoptosis, and decreased plasma cytokine levels. In parallel, IL-2 secretion and
      the lymphocyte mitogenic response improved. Between 4 and 7 months,
      immunoglobulin G antibodies to bovine ADA developed and resulted in the complete
      reversal of immune recovery.

PMID- 16002637
TI  - characterization of acute-phase humoral immunity to monkeypox: use of
      immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox
      infection during the 2003 North American outbreak.
AB  - A monkeypox outbreak occurred in the United States in 2003. Patient's sera were
      sent to the Centers for Disease Control and Prevention as a part of outbreak
      response measures. Clinical and epidemiologic information was abstracted from the
      case investigation forms. Serum samples from patients were tested by using an
      immunoglobulin M (IgM)-capture and an IgG enzyme-linked immunosorbent assay ELISA
      against Orthopoxvirus antigen. The detection of antiviral IgG and IgM antibodies
      and the kinetics of the antiviral IgG and IgM antibody responses were evaluated.
      Patients were classified as confirmed, probable, or suspect cases or were
      excluded as cases based on laboratory test results and epidemiologic and clinical
      criteria. A total of 37 confirmed case patients with monkeypox were identified,
      and 116 patients were excluded as case patients based on molecular testing or
      insufficient epidemiology and clinical data to warrant classification as a
      suspect or probable case. Of 37 confirmed case patients, 36 had a known history
      (presence or absence) of smallpox vaccination. Of those, 29 of the 36 either had
      or developed an IgG response, while 34 of the 36 developed an IgM response,
      regardless of vaccination status. Serum collected > or =5 days for IgM detection
      or serum collected > or =8 days after rash onset for IgG detection was most
      efficient for the detection of monkeypox virus infection. IgM ELISA detects
      recent infection with orthopoxviruses and, in this case, recent infection with
      monkeypox virus. In addition, analysis of paired sera for IgG and IgM detected
      seroconversion, another indicator of recent infection. The ELISA results
      correlated with the virologic PCR and viral culture results, indicating its
      diagnostic capabilities for monkeypox and potentially other orthopoxvirus
      infections due to zoonotic transmission or bioterrorism events.

PMID- 16002638
TI  - Role of the Nfa1 protein in pathogenic Naegleria fowleri cocultured with CHO
      target cells.
AB  - Naegleria fowleri, a free-living amoeba, exists as a virulent pathogen which
      causes fatal primary amoebic meningoencephalitis in experimental animals and
      humans. Using infected and immune mouse sera, we previously cloned an nfa1 gene
      from a cDNA library of N. fowleri by immunoscreening. The nfa1 gene (360 bp)
      produced a recombinant 13.1-kDa protein, and the Nfa1 protein showed pseudopodium
      specific immunolocalization on a trophozoite of N. fowleri. In this study, the
      role of the Nfa1 protein as a cell contact mechanism of N. fowleri cocultured
      with target cells was observed by an immunofluorescence assay with an anti-Nfa1
      polyclonal antibody. Using confocal microscopic findings, the Nfa1 protein was
      located on the pseudopodia of N. fowleri trophozoites. The Nfa1 protein in N.
      fowleri trophozoites cocultured with CHO target cells was also located on
      pseudopodia, as well as in a food cup formed as a phagocytic structure in close
      contact with target cells. The amount of nfa1 mRNA of N. fowleri was strongly
      increased 6 h after coculture.

PMID- 16002639
TI  - Enzyme-linked immunosorbent assay based on a chimeric antigen bearing antigenic
      regions of structural proteins Erns and E2 for serodiagnosis of classical swine
      fever virus infection.
AB  - The antigenic region (residues 109 to 160) of classical swine fever virus (CSFV)
      protein E(rns) and the N-terminal antigenic region (residues 1 to 136) of protein
      E2 were constructed in the form of a fused, chimeric protein, C21E(rns)E2, for
      use as an enzyme-linked immunosorbent assay (ELISA) antigen for the serodiagnosis
      of CSFV infection. Tested with 238 negative-field (CSFV-free) sera from Canadian
      sources, the specificity of the ELISA was determined to be 93.7%. All 20 sera
      from experimentally infected pigs representing a variety of animals, virus
      strains, and days postinfection (dpi; range, 7 to 210) were detected as positive
      (100%). In contrast, an ELISA based on an E(rns) fragment (E(rns)(aa 109-160)) or
      an E2 fragment (E2(aa 1-221)) identified only 18 (90%) of 20 sera from infected
      pigs as positive, missing two targets collected at 7 dpi. These data suggest that
      use of the chimeric antigen C21E(rns)E2 would improve serodiagnostic sensitivity
      and allow for the detection of CSFV infection as early as 7 dpi.

PMID- 16002640
TI  - Immunoglobulin M enzyme-linked immunosorbent assay using recombinant polypeptides
      for diagnosis of dengue.
AB  - We demonstrate that a mixture of four recombinant dengue virus E polypeptides
      corresponding to the N-terminal region of the envelope protein from all serotypes
      substitutes for standard antigens in two immunoglobulin M enzyme-linked
      immunosorbent assay formats with 100% concordance, making these polypeptides a
      useful and accessible reagent for serological diagnosis of dengue in endemic
      countries.

PMID- 16002641
TI  - Development of rapid immunochromatographic test with recombinant NcSAG1 for
      detection of antibodies to Neospora caninum in cattle.
AB  - An immunochromatographic test (ICT) with recombinant surface antigen 1 of
      Neospora caninum (NcSAG1) was developed for the rapid detection of antibodies to
      N. caninum in cattle. The ICT was used to clearly discriminate between
      immunofluorescent-antibody test (IFAT)-positive bovine sera and IFAT-negative
      bovine sera. Serum samples collected from cattle in Yanbian, China, were examined
      by the ICT. Of the 96 serum samples, 23 (24.0%) were positive by the ICT, and 19
      (19.8%) samples were positive by a previously developed enzyme-linked
      immunosorbent assay (ELISA). Eighteen of 19 ELISA-positive samples were positive
      according to the ICT. A good agreement was found between the results of the ICT
      and the ELISA. The results presented here suggest that the ICT with recombinant
      truncated NcSAG1 fused to glutathione S-transferase is a useful and reliable
      method for the detection of antibodies to N. caninum in cattle.

PMID- 16002642
TI  - Manganese transport and trafficking: lessons learned from Saccharomyces
      cerevisiae.

PMID- 16002644
TI  - Unique aspects of gene expression during Candida albicans mating and possible
      G(1) dependency.
AB  - Taking advantage of the high frequency of conjugation tube formation in mating
      mixtures and alpha-pheromone-treated a/a cells derived from saturation phase
      cultures of opaque cells of Candida albicans, 56 up-regulated and 30 down
      regulated genes were identified employing microarray and Northern analyses.
      Combining these results with previous profiling studies of pheromone-induced
      cells, a more comprehensive transcript profile was developed for comparison with
      Saccharomyces cerevisiae. This comparison revealed the following: (i) that while
      a majority of mating-associated genes are regulated similarly between the two
      species, a significant minority are regulated dissimilarly; (ii) that
      filamentation genes are uniquely up-regulated and opaque-specific genes uniquely
      down-regulated during C. albicans mating; and (iii) that a newly identified class
      of genes is selectively down-regulated in opaque, but not white, cells that have
      entered saturation phase in a growth culture and then are up-regulated by
      pheromone. The observations that opaque cells are uniquely mating competent, that
      saturation phase facilitates mating, and that a newly identified group of genes
      is down-regulated only in opaque cells that have entered saturation phase led us
      to hypothesize that entering saturation phase may be requisite for mating. A test
      of this hypothesis revealed, however, that cells, whether in the exponential or
      saturation phase, may simply have to be in G(1) of the cell cycle to respond to
      pheromone and that the response includes G(1) arrest. These results add to the
      lists of similarities and dissimilarities between the mating processes of C.
      albicans and S. cerevisiae and underscore the unique regulation of filamentation
      and switching genes in the C. albicans mating process.

PMID- 16002643
TI  - Saccharomyces cerevisiae Rab-GDI displacement factor ortholog Yip3p forms
      distinct complexes with the Ypt1 Rab GTPase and the reticulon Rtn1p.
AB  - Rab GTPases are crucial regulators of organelle biogenesis, maintenance, and
      transport. Multiple Rabs are expressed in all cells, and each is localized to a
      distinct set of organelles, but little is known regarding the mechanisms by which
      Rabs are targeted to their resident organelles. Integral membrane proteins have
      been postulated to serve as receptors that recruit Rabs from the cytosol in a
      complex with the Rab chaperone, GDI, to facilitate the dissociation of Rab and
      GDI, hence facilitating loading of Rabs on membranes. We show here that the yeast
      (Saccharomyces cerevisiae) Golgi Rab GTPase Ypt1p can be copurified with the
      integral membrane protein Yip3p from detergent cell extracts. In addition, a
      member of the highly conserved reticulon protein family, Rtn1p, is also
      associated with Yip3p in vivo. However, Ypt1p did not copurify with Rtn1p,
      indicating that Yip3p is a component of at least two different protein complexes.
      Yip3p and Rtn1p are only partially colocalized in cells, with Yip3p localized
      predominantly to the Golgi and secondarily to the endoplasmic reticulum, whereas
      Rtn1p is localized predominantly to the endoplasmic reticulum and secondarily to
      the Golgi. Surprisingly, the intracellular localization of Rabs was not perturbed
      in yip3Delta or rtn1Delta mutants, suggesting that these proteins do not play a
      role in targeting Rabs to intracellular membranes. These data indicate that Yip3p
      may have multiple functions and that its interaction with Rabs is not critical
      for their recruitment to organelle membranes.

PMID- 16002645
TI  - Cell cycle dynamics and quorum sensing in Candida albicans chlamydospores are
      distinct from budding and hyphal growth.
AB  - The regulation of morphogenesis in the human fungal pathogen Candida albicans is
      under investigation to better understand how the switch between budding and
      hyphal growth is linked to virulence. Therefore, in this study we examined the
      ability of C. albicans to undergo a distinct type of morphogenesis to form large
      thick-walled chlamydospores whose role in infection is unclear, but they act as a
      resting form in other species. During chlamydospore morphogenesis, cells switch
      to filamentous growth and then develop elongated suspensor cells that give rise
      to chlamydospores. These filamentous cells were distinct from true hyphae in that
      they were wider and were not inhibited by the quorum-sensing factor farnesol.
      Instead, farnesol increased chlamydospore production, indicating that quorum
      sensing can also have a positive role. Nuclear division did not occur across the
      necks of chlamydospores, as it does in budding. Interestingly, nuclei divided
      within the suspensor cells, and then one daughter nucleus subsequently migrated
      into the chlamydospore. Septins were not detected near mitotic nuclei but were
      localized at chlamydospore necks. At later stages, septins localized throughout
      the chlamydospore plasma membrane and appeared to form long filamentous
      structures. Deletion of the CDC10 or CDC11 septins caused greater curvature of
      cells growing in a filamentous manner and morphological defects in suspensor
      cells and chlamydospores. These studies identify aspects of chlamydospore
      morphogenesis that are distinct from bud and hyphal morphogenesis.

PMID- 16002646
TI  - Release from quorum-sensing molecules triggers hyphal formation during Candida
      albicans resumption of growth.
AB  - Candida albicans is a pathogenic fungus able to change morphology in response to
      variations in its growth environment. Simple inoculation of stationary cells into
      fresh medium at 37 degrees C, without any other manipulations, appears to be a
      powerful but transient inducer of hyphal formation; this process also plays a
      significant role in classical serum induction of hyphal formation. The mechanism
      appears to involve the release of hyphal repression caused by quorum-sensing
      molecules in the growth medium of stationary-phase cells, and farnesol has a
      strong but incomplete role in this process. We used DNA microarray technology to
      study both the resumption of growth of Candida albicans cells and molecular
      regulation involving farnesol. Maintaining farnesol in the culture medium during
      the resumption of growth both delays and reduces the induction of hypha-related
      genes yet triggers expression of genes encoding drug efflux components. The
      persistence of farnesol also prevents the repression of histone genes during
      hyphal growth and affects the expression of putative or demonstrated
      morphogenesis-regulating cyclin genes, such as HGC1, CLN3, and PCL2. The results
      suggest a model explaining the triggering of hyphae in the host based on quorum
      sensing molecules.

PMID- 16002647
TI  - Functional characterization of an evolutionarily distinct phosphopantetheinyl
      transferase in the apicomplexan Cryptosporidium parvum.
AB  - Recently, two types of fatty acid synthases (FASs) have been discovered from
      apicomplexan parasites. Although significant progress has been made in
      characterizing these apicomplexan FASs, virtually nothing was previously known
      about the activation and regulation of these enzymes. In this study, we report
      the discovery and characterization of two distinct types of phosphopantetheinyl
      transferase (PPTase) that are responsible for synthesizing holo-acyl carrier
      protein (ACP) from three apicomplexan parasites: surfactin production element
      (SFP) type in Cryptosporidium parvum (CpSFP-PPT), holo-ACP synthase (ACPS)-type
      in Plasmodium falciparum (PfACPS-PPT), and both SFP and ACPS types in Toxoplasma
      gondii (TgSFP-PPT and TgACPS-PPT). CpSFP-PPT and TgSFP-PPT are monofunctional,
      cytosolic, and phylogenetically related to animal PPTases. However, PfACPS-PPT
      and TgACPS-PPT are bifunctional (fused with a metal-dependent hydrolase), likely
      targeted to the apicoplast, and more closely related to proteobacterial PPTases.
      The function of apicomplexan PPTases has been confirmed by detailed functional
      analysis using recombinant CpSFP-PPT expressed from an artificially synthesized
      gene with codon usage optimized for Escherichia coli. The recombinant CpSFP-PPT
      was able to activate the ACP domains from the C. parvum type I FAS in vitro using
      either CoA or acetyl-CoA as a substrate, or in vivo when coexpressed in bacteria,
      with kinetic characteristics typical of PPTases. These observations suggest that
      the two types of fatty acid synthases in the Apicomplexa are activated and
      regulated by two evolutionarily distinct PPTases.

PMID- 16002648
TI  - Autocrine, mitogenic pheromone receptor loop of the ciliate Euplotes raikovi:
      pheromone-induced receptor internalization.
AB  - The ciliate Euplotes raikovi produces a family of diffusible signal proteins
      (pheromones) that function as prototypic growth factors. They may either promote
      cell growth, by binding to pheromone receptors synthesized by the same cells from
      which they are secreted (autocrine activity), or induce a temporary cell shift
      from the growth stage to a mating (sexual) one by binding to pheromone receptors
      of other, conspecific cells (paracrine activity). In cells constitutively
      secreting the pheromone Er-1, it was first observed that the expression of the Er
      1 receptor "p15," a type II membrane protein of 130 amino acids, is
      quantitatively correlated with the extracellular concentration of secreted
      pheromone. p15 expression on the cell surface rapidly and markedly increased
      after the removal of secreted Er-1 and gradually decreased in parallel with new
      Er-1 secretion. It was then shown that p15 is internalized through endocytic
      vesicles following Er-1 binding and that the internalization of p15/Er-1
      complexes is specifically blocked by the paracrine p15 binding of Er-2, a
      pheromone structurally homologous to, and thus capable of fully antagonizing, Er
      1. Based on previous findings that the p15 pheromone-binding site is structurally
      equivalent to Er-1 and that Er-1 molecules polymerize in crystals following a
      pattern of cooperative interaction, it was proposed that p15/Er-1 complexes are
      internalized as a consequence of their unique property (not shared by p15/Er-2
      complexes) of undergoing clustering.

PMID- 16002649
TI  - A CDC42 homologue in Claviceps purpurea is involved in vegetative differentiation
      and is essential for pathogenicity.
AB  - Claviceps purpurea, a biotrophic pathogen of cereals, has developed a unique
      pathogenic strategy including an extended period of unbranched directed growth in
      the host's style and ovarian tissue to tap the vascular system. Since the small
      GTPase Cdc42 has been shown to be involved in cytoskeleton organization and
      polarity in other fungi, we investigated the role of Cdc42 in the development and
      pathogenicity of C. purpurea. Expression of heterologous dominant-active (DA) and
      dominant-negative (DN) alleles of Colletotrichum trifolii in a wild strain of C.
      purpurea had significant impact on vegetative differentiation: whereas DA Ctcdc42
      resulted in loss of conidiation and in aberrant cell shape, expression of DN
      Ctcdc42 stimulated branching and conidiation. Deletion of the endogenous Cpcdc42
      gene was not lethal but led to a phenotype comparable to that of DN Ctcdc42
      transformants. DeltaCpcdc42 mutants were nonpathogenic; i.e., they induced no
      disease symptoms. Cytological analysis (light microscopy and electron microscopy)
      revealed that the mutants can penetrate and invade the stylar tissue. However,
      invasive growth was arrested in an early stage, presumably induced by plant
      defense reactions (necrosis or increased production of reactive oxygen species),
      which were never observed in wild-type infection. The data show a significant
      impact of Cpcdc42 on vegetative differentiation and pathogenicity in C. purpurea.

PMID- 16002650
TI  - Aspergillus nidulans uvsBATR and scaANBS1 genes show genetic interactions during
      recovery from replication stress and DNA damage.
AB  - The ATM/ATR kinases and the Mre11 (Mre11-Rad50-Nbs1) protein complex are central
      players in the cellular DNA damage response. Here we characterize possible
      interactions between Aspergillus nidulans uvsB(ATR) and the Mre11 complex
      (scaA(NBS1)). We demonstrate that there is an epistatic relationship between
      uvsB(ATR), the homolog of the ATR/MEC1 gene, and scaA(NBS1), the homolog of the
      NBS1/XRS2 gene, for both repair and checkpoint functions and that correct
      ScaA(NBS1) expression during recovery from replication stress depends on
      uvsB(ATR). In addition, we also show that the formation of UvsC foci during
      recovery from replication stress is dependent on both uvsB(ATR) and scaA(NBS1)
      function. Furthermore, ScaA(NBS1) is also dependent on uvsB(ATR) for nuclear
      focus formation upon the induction of DNA double-strand breaks by phleomycin. Our
      results highlight the extensive genetic interactions between UvsB and the Mre11
      complex that are required for S-phase progression and recovery from DNA damage.

PMID- 16002651
TI  - Centrin scaffold in Chlamydomonas reinhardtii revealed by immunoelectron
      microscopy.
AB  - In the flagellate green alga Chlamydomonas reinhardtii the Ca(2+)-binding EF-hand
      protein centrin is encoded by a single-copy gene. Previous studies have localized
      the protein to four distinct structures in the flagellar apparatus: the nucleus
      basal body connector, the distal connecting fiber, the flagellar transitional
      region, and the axoneme. To explain the disjunctive distribution of centrin, the
      interaction of centrin with as yet unknown specific centrin-binding proteins has
      been implied. Here, we demonstrate using serial section postembedding
      immunoelectron microscopy of isolated cytoskeletons that centrin is located in
      additional structures (transitional fibers and basal body lumen) and that the
      centrin-containing structures of the basal apparatus are likely part of a
      continuous filamentous scaffold that extends from the nucleus to the flagellar
      bases. In addition, we show that centrin is located in the distal lumen of the
      basal body in a rotationally asymmetric structure, the V-shaped filament system.
      This novel centrin-containing structure has also been detected near the distal
      end of the probasal bodies. Taken together, these results suggest a role for a
      rotationally asymmetric centrin "seed" in the growth and development of the
      centrin scaffold following replication of the basal apparatus.

PMID- 16002652
TI  - Nuclear-gene targeting by using single-stranded DNA avoids illegitimate DNA
      integration in Chlamydomonas reinhardtii.
AB  - Homologous DNA recombination (HR) allows the deletion (knockout), repair
      (rescuing), and modification of a selected gene, thereby rendering a functional
      analysis of the gene product possible. However, targeting of nuclear genes has
      been an inefficient process in most eukaryotes, including algae, plants, and
      animals, due to the dominance of integration of the applied DNA into
      nonhomologous regions of the genome. We have shown for the green alga
      Chlamydomonas reinhardtii by repairing a previously introduced truncated
      aminoglycoside 3'-phosphotransferase gene, aphVIII, that single-stranded DNA can
      recombine with a homologous endogenous DNA region of interest. Nonhomologous DNA
      integration appeared to be more than 100-fold reduced compared with the use of
      double-stranded DNA, thus allowing isolation of the homologous recombinants. We
      propose that this method will be applicable to direct targeting of nuclear C.
      reinhardtii genes.

PMID- 16002654
TI  - Hyphal Growth in the Fission Yeast Schizosaccharomyces pombe.
AB  - The fission yeast Schizosaccharomyces pombe grows in a single-celled form or can
      mate and undergo meiosis and sporulation. Here we show that wild-type S. pombe
      can also differentiate to form elaborately branched hyphae which invade deep into
      solid medium. Branches appear in the hyphae adjacent to unseparated septa.
      Electron microscopy reveals unusual multivesicular structures within the hyphae.
      Nitrogen deprivation appears to be the main stimulus for hyphal growth. No
      mitogen-activated protein kinase is necessary for the response. Inhibition of
      cyclic AMP (cAMP) production or signaling prevents the response, and exogenous
      cAMP promotes it, suggesting that detection of a good carbon source is required
      for hyphal growth but not for mating.

PMID- 16002653
TI  - Hyphal guidance and invasive growth in Candida albicans require the Ras-like
      GTPase Rsr1p and its GTPase-activating protein Bud2p.
AB  - Candida albicans, the most prevalent fungal pathogen of humans, causes
      superficial mycoses, invasive mucosal infections, and disseminated systemic
      disease. Many studies have shown an intriguing association between C. albicans
      morphogenesis and the pathogenesis process. For example, hyphal cells have been
      observed to penetrate host epithelial cells at sites of wounds and between cell
      junctions. Ras- and Rho-type GTPases regulate many morphogenetic processes in
      eukaryotes, including polarity establishment, cell proliferation, and directed
      growth in response to extracellular stimuli. We found that the C. albicans Ras
      like GTPase Rsr1p and its predicted GTPase-activating protein Bud2p localized to
      the cell cortex, at sites of incipient daughter cell growth, and provided
      landmarks for the positioning of daughter yeast cells and hyphal cell branches,
      similar to the paradigm in the model yeast Saccharomyces cerevisiae. However, in
      contrast to S. cerevisiae, CaRsr1p and CaBud2p were important for morphogenesis:
      C. albicans strains lacking Rsr1p or Bud2p had abnormal yeast and hyphal cell
      shapes and frequent bends and promiscuous branching along the hypha and were
      unable to invade agar. These defects were associated with abnormal actin patch
      polarization, unstable polarisome localization at hyphal tips, and mislocalized
      septin rings, consistent with the idea that GTP cycling of Rsr1p stabilizes the
      axis of polarity primarily to a single focus, thus ensuring normal cell shape and
      a focused direction of polarized growth. We conclude that the Rsr1p GTPase
      functions as a polarity landmark for hyphal guidance and may be an important
      mediator of extracellular signals during processes such as host invasion.

PMID- 16002655
TI  - Deletion and allelic exchange of the Aspergillus fumigatus veA locus via a novel
      recyclable marker module.
AB  - Detailed evaluation of gene functions in an asexual fungus requires advanced
      methods of molecular biology. For the generation of targeted gene deletions in
      the opportunistic pathogen Aspergillus fumigatus we designed a novel blaster
      module allowing dominant selection of transformants due to resistance to
      phleomycin as well as dominant (counter)selection of a Cre recombinase-mediated
      marker excision event. For validation purposes we have deleted the A. fumigatus
      pabaA gene in a wild-type isolate by making use of this cassette. The resulting
      pabaA::loxP strain served as the recipient for subsequent targeting of the velvet
      locus. Homologous reconstitution of the deleted gene was performed by an allele
      whose expression is driven in a nitrogen source-dependent manner, as validated by
      Northern analyses. Overexpression of the veA locus in A. fumigatus does not
      result in any obvious phenotype, whereas the sporulation capacities of the veA
      null mutant are reduced on nitrate-containing medium, a phenotype that is
      completely restored in the reconstituted strain.

PMID- 16002657
TI  - DNA vaccines: progress and challenges.
AB  - In the years following the publication of the initial in vivo demonstration of
      the ability of plasmid DNA to generate protective immune responses, DNA vaccines
      have entered into a variety of human clinical trials for vaccines against various
      infectious diseases and for therapies against cancer, and are in development for
      therapies against autoimmune diseases and allergy. They also have become a widely
      used laboratory tool for a variety of applications ranging from proteomics to
      understanding Ag presentation and cross-priming. Despite their rapid and
      widespread development and the commonplace usage of the term "DNA vaccines,"
      however, the disappointing potency of the DNA vaccines in humans underscores the
      challenges encountered in the efforts to translate efficacy in preclinical models
      into clinical realities. This review will provide a brief background of DNA
      vaccines including the insights gained about the varied immunological mechanisms
      that play a role in their ability to generate immune responses.

PMID- 16002656
TI  - Galactomannoproteins of Aspergillus fumigatus.
AB  - Galactofuranose-containing molecules have been repeatedly shown to be important
      antigens among human fungal pathogens, including Aspergillus fumigatus.
      Immunogenic galactofuran determinants have been poorly characterized chemically,
      however. We reported here the characterization of two glycoproteins of A.
      fumigatus with an N-glycan containing galactofuranose. These proteins are a
      phospholipase C and a phytase. Chemical characterization of the N-glycan
      indicates that it is a mixture of Hex(5-13)HexNAc(2) oligosaccharides, the major
      molecular species corresponding to Hex(6-8)HexNAc(2). The N-glycan contained one
      galactofuranose unit that was in a terminal nonreducing position attached to the
      2 position of Man. This single terminal nonreducing galactofuranose is essential
      for the immunoreactivity of the N-glycans assessed either with a monoclonal
      antibody that recognizes a tetra-beta-1,5-galactofuran chain of galactomannan or
      with Aspergillus-infected patient sera.

PMID- 16002658
TI  - Cutting edge: IL-12 induces CD4+CD25- T cell activation in the presence of T
      regulatory cells.
AB  - IL-12p40 cytokines have been implicated in the development of organ-specific
      autoimmune diseases as well as pathogen-specific adaptive immunity. In addition
      to inducing IFN-gamma, IL-12 stimulates effector CD4(+) T cells to express
      adhesion molecules and homing receptors that facilitate their migration to sites
      of inflammation. In this study, we expand upon those observations by
      demonstrating an alternative pathway by which IL-12 could promote Th1
      inflammatory responses in mice, namely, by restoring proliferation and cytokine
      expression by effector T cells in the presence of CD4(+)CD25(+) regulatory T
      cells (Treg). This effect of IL-12 was not replicated by IL-23 or IFN-gamma and
      was dependent on signaling through the IL-12R expressed on CD25(-) responder
      cells, but not on Treg. Our studies suggest that IL-12 could act in concert with
      other proinflammatory factors to stimulate CD4(+)CD25(-) T cell activation in the
      presence of Treg.

PMID- 16002659
TI  - E2F1 and E2F2 are differentially required for homeostasis-driven and antigen
      induced T cell proliferation in vivo.
AB  - Homeostasis-driven T cell proliferation occurs in response to a lymphopenic
      environment and is mediated by TCR and IL-7 signaling. In this report, we
      demonstrate a defect in the proliferation of murine naive and memory T cells
      lacking both E2F1 and E2F2 in response to lymphopenic conditions, suggesting that
      E2F1 and E2F2 function redundantly downstream of TCR and/or IL-7 signaling during
      homeostasis-driven proliferation. In contrast, T cell proliferation in response
      to antigenic stimulation is either unaffected (in vivo) or potentiated (ex vivo)
      by loss of E2F1 and E2F2, indicating divergent requirements for these E2F factors
      in T cell proliferation mediated by distinct stimuli. E2F1/E2F2 double knockout
      (DKO) T cells enter S phase in response to homeostatic signaling, but fail to
      divide, suggesting that S phase progression is either incomplete or defective. In
      addition, E2F1/E2F2 DKO mice do not recover normal T cell numbers following
      exposure to a sublethal dose of radiation, indicating that this defect in
      homeostasis-driven proliferation is physiologically relevant. Consistent with
      their failure in cell cycle progression, the differentiation of DKO T cells into
      memory T cells in response to homeostatic signals is significantly reduced. These
      observations support the idea that proliferation is required for memory T cell
      formation and also have implications for the development of clinical strategies
      to minimize the occurrence of lymphopenia-induced autoimmunity.

PMID- 16002660
TI  - Active Ca2+/calmodulin-dependent protein kinase II gamma B impairs positive
      selection of T cells by modulating TCR signaling.
AB  - T cell development is regulated at two critical checkpoints that involve
      signaling events through the TCR. These signals are propagated by kinases of the
      Src and Syk families, which activate several adaptor molecules to trigger Ca(2+)
      release and, in turn, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      activation. In this study, we show that a constitutively active form of CaMKII
      antagonizes TCR signaling and impairs positive selection of thymocytes in mice.
      Following TCR engagement, active CaMKII decreases TCR-mediated CD3zeta chain
      phosphorylation and ZAP70 recruitment, preventing further downstream events.
      Therefore, we propose that CaMKII belongs to a negative-feedback loop that
      modulates the strength of the TCR signal through the tyrosine phosphatase Src
      homology 2 domain-containing phosphatase 2 (SHP-2).

PMID- 16002661
TI  - Mechanisms of the antitumor responses and host-versus-graft reactions induced by
      recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative
      conditioning: a critical role for recipient CD4+ T cells and recipient leukocyte
      infusion-derived IFN-gamma-producing CD8+ T cells.
AB  - Surprisingly, antitumor responses can occur in patients who reject donor grafts
      following nonmyeloablative hemopoietic cell transplantation. In murine mixed
      chimeras prepared with nonmyeloablative conditioning, we previously showed that
      recipient leukocyte infusions (RLI) induced loss of donor chimerism, IFN-gamma
      production, and antitumor responses against host-type tumors. However, the
      mechanisms behind this phenomenon remain to be determined. We now demonstrate
      that the effects of RLI are mediated by distinct and complex mechanisms. Donor
      marrow rejection is induced by RLI-derived alloactivated T cells, which activate
      non-RLI-derived, recipient IFN-gamma-producing cells. RLI-derived CD8 T cells
      induce the production of IFN-gamma by both RLI and non-RLI-derived recipient
      cells. The antitumor responses of RLI involve mainly RLI-derived IFN-gamma
      producing CD8 T cells and recipient-derived CD4 T cells and do not involve donor
      T cells. The pathways of donor marrow and tumor rejection lead to the development
      of tumor-specific cell-mediated cytotoxic responses that are not due to bystander
      killing by alloreactive T cells.

PMID- 16002662
TI  - Induction of a regulatory phenotype in human CD4+ T cells by streptococcal M
      protein.
AB  - Regulatory T cells (Tregs) participate in the control of the immune response. In
      the human system, an IL-10-secreting, T regulatory type 1 cell (Tr1)-like subset
      of Tregs can be induced by concurrent cross-linking of the TCR and CD46 on naive
      CD4(+) T cells. Because many viral and bacterial pathogens, including the major
      human pathogen Streptococcus pyogenes, bind to CD46, we asked whether this
      bacterium can directly induce Tr1-like cells through the streptococcal ligand for
      CD46, the M protein. The M5 and M22 proteins were found to induce T cells to
      develop into the IL-10-producing Tr1-like phenotype. Moreover, whole M5
      expressing bacteria, but not isogenic M-negative bacteria, led to proliferation
      and IL-10 secretion by T cells. The interaction between the M5 protein and T
      cells was dependent on CD46 and the conserved C repeat region of M5. Supernatants
      derived from T cells stimulated with M proteins or M protein-expressing bacteria
      suppressed bystander T cell proliferation through IL-10 secretion. In addition,
      activation of CD46 through streptococcal M protein induced the expression of
      granzyme B, providing a second means for these cells to regulate an immune
      response. These findings suggest that binding to CD46 and exploiting its
      signaling pathway may represent a strategy employed by a number of important
      human pathogens to induce directly an immunosuppressive/regulatory phenotype in T
      cells.

PMID- 16002663
TI  - The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met inhibits human monocyte-derived
      dendritic cell maturation via formyl peptide receptor and formyl peptide receptor
      like 2.
AB  - Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) has been reported to stimulate monocytes,
      neutrophils, and dendritic cells (DCs). However, although WKYMVm has been
      reported to function as a DC chemoattractant, its role on DC maturation has not
      been examined. In this study, we investigated the effects of WKYMVm on human DC
      maturation. The costimulation of DCs with WKYMVm and LPS dramatically inhibited
      LPS-induced IL-12 production, CD86 and HLA-DR surface expression, and DC-mediated
      T cell proliferation. However, DC phagocytic activity was increased by WKYMVm
      stimulation. These findings demonstrate that WKYMVm inhibits DC maturation by
      LPS. In terms of the mechanism underlying DC maturation inhibition by WKYMVm, we
      found that LPS-induced DC maturation was negatively regulated by WKYMVm
      stimulated ERK activity. Moreover, the costimulation of DCs with WKYMVm and LPS
      dramatically inhibited the LPS-induced accumulations of IL-12 mRNA, thus
      suggesting that WKYMVm inhibits LPS-induced IL-12 production at the
      transcriptional level. We also found that DCs express two WKYMVm receptors,
      formyl peptide receptor (FPR) and FPR-like 2 (FPRL2). In addition, formyl-Met-Leu
      Phe (a FPR ligand), Trp-Lys-Tyr-Met-Val-Met, Hp(2-20) peptide, and F2L (three
      FPRL2 ligands) inhibited LPS-induced IL-12 production in DCs. Taken together, our
      findings indicate that the activations of FPR and FPRL2 inhibit LPS-induced DC
      maturation, and suggest that these two receptors should be regarded as important
      potential therapeutic targets for the modulation of DC maturation.

PMID- 16002664
TI  - In vivo hydrodynamic delivery of cDNA encoding IL-2: rapid, sustained
      redistribution, activation of mouse NK cells, and therapeutic potential in the
      absence of NKT cells.
AB  - In the present study, we have tested the ability of hydrodynamically delivered IL
      2 cDNA to modulate the number and function of murine leukocyte subsets in
      different organs and in mice of different genetic backgrounds, and we have
      evaluated effects of this mode of gene delivery on established murine tumor
      metastases. Hydrodynamic administration of the IL-2 gene resulted in the rapid
      and transient production of up to 160 ng/ml IL-2 in the serum. The appearance of
      IL-2 was followed by transient production of IFN-gamma and a dramatic and
      sustained increase in NK cell numbers and NK-mediated cytolytic activity in liver
      and spleen leukocytes. In addition, significant increases in other lymphocyte
      subpopulations (e.g., NKT, T, and B cells) that are known to be responsive to IL
      2 were observed following IL-2 cDNA plasmid delivery. Finally, hydrodynamic
      delivery of only 4 mug of the IL-2 plasmid to mice bearing established lung and
      liver metastases was as effective in inhibiting progression of metastases as was
      the administration of large amounts (100,000 IU/twice daily) of IL-2 protein.
      Studies performed in mice bearing metastatic renal cell tumors demonstrated that
      the IL-2 cDNA plasmid was an effective treatment against liver metastasis and
      moderately effective against lung metastasis. Collectively, these results
      demonstrate that hydrodynamic delivery of relatively small amounts of IL-2 cDNA
      provides a simple and inexpensive method to increase the numbers of NK and NKT
      cells, to induce the biological effects of IL-2 in vivo for use in combination
      with other biological agents, and for studies of its antitumor activity.

PMID- 16002665
TI  - Inefficient cross-presentation limits the CD8+ T cell response to a subdominant
      tumor antigen epitope.
AB  - CD8(+) T lymphocytes (T(CD8)) responding to subdominant epitopes provide
      alternate targets for the immunotherapy of cancer, particularly when self
      tolerance limits the response to immunodominant epitopes. However, the mechanisms
      that promote T(CD8) subdominance to tumor Ags remain obscure. We investigated the
      basis for the lack of priming against a subdominant tumor epitope following
      immunization of C57BL/6 (B6) mice with SV40 large tumor Ag (T Ag)-transformed
      cells. Immunization of B6 mice with wild-type T Ag-transformed cells primes
      T(CD8) specific for three immunodominant T Ag epitopes (epitopes I, II/III, and
      IV) but fails to induce T(CD8) specific for the subdominant T Ag epitope V. Using
      adoptively transferred T(CD8) from epitope V-specific TCR transgenic mice and
      immunization with T Ag-transformed cells, we demonstrate that the subdominant
      epitope V is weakly cross-presented relative to immunodominant epitopes derived
      from the same protein Ag. Priming of naive epitope V-specific TCR transgenic
      T(CD8) in B6 mice required cross-presentation by host APC. However, robust
      expansion of these T(CD8) required additional direct presentation of the
      subdominant epitope by T Ag-transformed cells and was only significant following
      immunization with T Ag-expressing cells lacking the immunodominant epitopes.
      These results indicate that limited cross-presentation coupled with competition
      by immunodominant epitope-specific T(CD8) contributes to the subdominant nature
      of a tumor-specific epitope. This finding has implications for vaccination
      strategies targeting T(CD8) responses to cancer.

PMID- 16002666
TI  - The type 1 cysteinyl leukotriene receptor triggers calcium influx and chemotaxis
      in mouse alpha beta- and gamma delta effector T cells.
AB  - Linker for activation of T cells (LAT) is essential for T cell activation. Mice
      with mutations of distinct LAT tyrosine residues (LatY136F and Lat3YF) develop
      lymphoproliferative disorders involving TCR alphabeta or gammadelta T cells that
      trigger symptoms resembling allergic inflammation. We analyzed whether these T
      cells share a pattern of gene expression that may account for their pathogenic
      properties. Both LatY136F alphabeta and Lat3YF gammadelta T cells expressed high
      levels of the type 1 cysteinyl leukotriene receptor (CysLT(1)). Upon binding to
      the 5(S)-hydroxy-6(R)-S-cysteinylglycyl-7,9-trans-11,14-cis-eicosatetraenoic acid
      (LTD(4)) cysteinyl leukotriene, CysLT(1) induced Ca(2+) flux and caused
      chemotaxis in both LatY136F alphabeta and Lat3YF gammadelta T cells. Wild-type in
      vitro-activated T cells, but not resting T cells, also migrated toward LTD(4)
      however with a lower magnitude than T cells freshly isolated from LatY136F and
      Lat3YF mice. These results suggest that CysLT(1) is likely involved in the
      recruitment of activated alphabeta and gammadelta T cells to inflamed tissues.

PMID- 16002667
TI  - Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo.
AB  - The immunoreceptor NKG2D stimulates activation of cytotoxic lymphocytes upon
      engagement with MHC class I-related NKG2D ligands of which at least some are
      expressed inducibly upon exposure to carcinogens, cell stress, or viruses. In
      this study, we investigated consequences of a persistent NKG2D ligand expression
      in vivo by using transgenic mice expressing MHC class I chain-related protein A
      (MICA) under control of the H2-K(b) promoter. Although MICA functions as a potent
      activating ligand of mouse NKG2D, H2-K(b)-MICA mice appear healthy without
      aberrations in lymphocyte subsets. However, NKG2D-mediated cytotoxicity of H2
      K(b)-MICA NK cells is severely impaired in vitro and in vivo. This deficiency
      concurs with a pronounced down-regulation of surface NKG2D that is also seen on
      activated CD8 T cells. As a consequence, H2-K(b)-MICA mice fail to reject MICA
      expressing tumors and to mount normal CD8 T cell responses upon Listeria
      infection emphasizing the importance of NKG2D in immunity against tumors and
      intracellular infectious agents.

PMID- 16002668
TI  - Bordetella pertussis adenylate cyclase toxin modulates innate and adaptive immune
      responses: distinct roles for acylation and enzymatic activity in
      immunomodulation and cell death.
AB  - Adenylate cyclase toxin (CyaA) of Bordetella pertussis belongs to the repeat in
      toxin family of pore-forming toxins, which require posttranslational acylation to
      lyse eukaryotic cells. CyaA modulates dendritic cell (DC) and macrophage function
      upon stimulation with LPS. In this study, we examined the roles of acylation and
      enzymatic activity in the immunomodulatory and lytic effects of CyaA. The
      adenylate cyclase activity of CyaA was necessary for its modulatory effects on
      murine innate immune cells. In contrast, acylation was not essential for the
      immunomodulatory function of CyaA, but was required for maximal caspase-3
      activation and cytotoxic activity. The wild-type acylated toxin (A-CyaA) and
      nonacylated CyaA (NA-CyaA), but not CyaA with an inactive adenylate cyclase
      domain (iAC-CyaA), enhanced TLR-ligand-induced IL-10 and inhibited IL-12, TNF
      alpha, and CCL3 production by macrophages and DC. In addition, both A-CyaA and NA
      CyaA, but not iAC-CyaA, enhanced surface expression of CD80 and decreased CpG
      stimulated CD40 and ICAM-1 expression on immature DC. Furthermore, both A-CyaA
      and NA-CyaA promoted the induction of murine IgG1 Abs, Th2, and regulatory T
      cells against coadministered Ags in vivo, whereas iAC-CyaA had more limited
      adjuvant activity. In contrast, A-CyaA and iAC-CyaA induced caspase-3 activation
      and cell death in macrophages, but these effects were considerably reduced or
      absent with NA-CyaA. Our findings demonstrate that the enzymatic activity plays a
      critical role in the immunomodulatory effects of CyaA, whereas acylation
      facilitates the induction of apoptosis and cell lysis, and as such, NA-CyaA has
      considerable potential as a nontoxic therapeutic molecule with potent anti
      inflammatory properties.

PMID- 16002669
TI  - Phenotype and homing of CD4 tumor-specific T cells is modulated by tumor bulk.
AB  - Technical difficulties in tracking endogenous CD4 T lymphocytes have limited the
      characterization of tumor-specific CD4 T cell responses. Using fluorescent MHC
      class II/peptide multimers, we defined the fate of endogenous Leishmania receptor
      for activated C kinase (LACK)-specific CD4 T cells in mice bearing LACK
      expressing TS/A tumors. LACK-specific CD44(high)CD62L(low) CD4 T cells
      accumulated in the draining lymph nodes and had characteristics of effector
      cells, secreting IL-2 and IFN-gamma upon Ag restimulation. Increased frequencies
      of CD44(high)CD62L(low) LACK-experienced cells were also detected in the spleen,
      lung, liver, and tumor itself, but not in nondraining lymph nodes, where the
      cells maintained a naive phenotype. The absence of systemic redistribution of
      LACK-specific memory T cells correlated with the presence of tumor. Indeed, LACK
      specific CD4 T cells with central memory features (IL-2(+)IFN-gamma(
      )CD44(high)CD62L(high) cells) accumulated in all peripheral lymph nodes of mice
      immunized with LACK-pulsed dendritic cells and after tumor resection. Together,
      our data demonstrate that although tumor-specific CD4 effector T cells producing
      IFN-gamma are continuously generated in the presence of tumor, central memory CD4
      T cells accumulate only after tumor resection. Thus, the continuous stimulation
      of tumor-specific CD4 T cells in tumor-bearing mice appears to hinder the
      systemic accumulation of central memory CD4 T lymphocytes.

PMID- 16002670
TI  - Phospholipase C-gamma 2 is a critical signaling mediator for murine NK cell
      activating receptors.
AB  - Phospholipase C-gamma (PLCgamma) is a key regulator of intracellular Ca(2+)
      mobilization. Two isoforms of PLCgamma have been identified, PLCgamma1 and
      PLCgamma2. Previously, in vitro studies indicated that activating NK cell
      receptors signal through both isoforms. However, PLCgamma2 deficiency alone was
      sufficient to induce a substantial impairment of NK cell-mediated cytotoxicity in
      vitro. Why PLCgamma2 is more important than PLCgamma1 for NK cell activation and
      whether PLCgamma2 is also critical for NK cell development, secretion of IFN
      gamma, and clearance of viral infections in vivo is not known. In this study, we
      report that PLCgamma2 is the predominant isoform expressed in murine NK cells.
      PLCgamma2 deficiency did not affect NK cell numbers in bone marrow and spleen,
      but acquisition of Ly49 receptors by NK cells was partially impaired. PLCgamma2
      deficient NK cells exhibited a dramatic impairment of cytolytic function and IFN
      gamma production upon ligation of activating receptors, whereas they did secrete
      IFN-gamma in response to cytokines. Consequently, mice lacking PLCgamma2
      controlled murine CMV infection substantially less effectively than did wild-type
      animals, and this defect was most evident in the spleen, where viral clearance
      mostly depends on NK cell lytic function. These results demonstrate that
      PLCgamma2 is crucial for development of the NK cell receptor repertoire and
      signaling of activating NK cell receptors, mediating optimal NK cell function in
      vivo.

PMID- 16002671
TI  - IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells.
AB  - Human naive CD8+ T cells are able to respond in an Ag-independent manner to IL-7
      and IL-15. Whereas IL-7 largely maintains CD8+ T cells in a naive phenotype, IL
      15 drives these cells to an effector phenotype characterized, among other
      features, by down-regulation of the costimulatory molecule CD28. We evaluated the
      influence of the CD4+ Th cell-derived common gamma-chain cytokine IL-21 on
      cytokine-induced naive CD8+ T cell activation. Stimulation with IL-21 did not
      induce division and only slightly increased IL-15-induced proliferation of naive
      CD8+ T cells. Strikingly, however, IL-15-induced down-modulation of CD28 was
      completely prevented by IL-21 at the protein and transcriptional level.
      Subsequent stimulation via combined TCR/CD3 and CD28 triggering led to a markedly
      higher production of IL-2 and IFN-gamma in IL-15/IL-21-stimulated cells compared
      with IL-15-stimulated T cells. Our data show that IL-21 modulates the phenotype
      of naive CD8+ T cells that have undergone IL-15 induced homeostatic proliferation
      and preserves their responsiveness to CD28 ligands.

PMID- 16002672
TI  - Expansion and hyperactivity of CD1d-restricted NKT cells during the progression
      of systemic lupus erythematosus in (New Zealand Black x New Zealand White)F1
      mice.
AB  - CD1d-restricted NKT cells expressing invariant TCR alpha-chain rearrangements
      (iNKT cells) have been reported to be deficient in humans with a variety of
      autoimmune syndromes and in certain strains of autoimmune mice. In addition,
      injection of mice with alpha-galactosylceramide, a specific glycolipid agonist of
      iNKT cells, activates these T cells and ameliorates autoimmunity in several
      different disease models. Thus, deficiency and reduced function in iNKT cells are
      considered to be risk factors for the development of such diseases. In this study
      we report that the development of systemic lupus erythematosus in (New Zealand
      Black (NZB) x New Zealand White (NZW))F(1) mice was paradoxically associated with
      an expansion and activation of iNKT cells. Although young (NZB x NZW)F(1) mice
      had normal levels of iNKT cells, these expanded with age and became
      phenotypically and functionally hyperactive. Activation of iNKT cells in (NZB x
      NZW)F(1) mice in vivo or in vitro with alpha-galactosylceramide indicated that
      the immunoregulatory role of iNKT cells varied over time, revealing a marked
      increase in their potential to contribute to production of IFN-gamma with
      advancing age and disease progression. This evolution of iNKT cell function
      during the progression of autoimmunity may have important implications for the
      mechanism of disease in this model of systemic lupus erythematosus and for the
      development of therapies using iNKT cell agonists.

PMID- 16002673
TI  - Analysis of the underlying cellular mechanisms of anti-CD154-induced graft
      tolerance: the interplay of clonal anergy and immune regulation.
AB  - Although it has been shown that CD4(+)CD25(+) regulatory T cells (T(reg))
      contribute to long-term graft acceptance, their impact on the effector
      compartment and the mechanism by which they exert suppression in vivo remain
      unresolved. Using a CD4(+) TCR transgenic model for graft tolerance, we have
      unveiled the independent contributions of anergy and active suppression to the
      fate of immune and tolerant alloreactive T cells in vivo. First, it is shown that
      anti-CD154-induced tolerance resulted in the abortive expansion of the
      alloreactive, effector T cell pool. Second, commensurate with reduced expansion,
      there was a loss of cytokine production, activation marker expression, and
      absence of memory T cell markers. All these parameters defined the tolerant
      alloreactive T cells and correlated with the inability to mediate graft
      rejection. Third, the tolerant alloreactive T cell phenotype that is induced by
      CD154 was reversed by the in vivo depletion of T(reg). Reversal of the tolerant
      phenotype was followed by rapid rejection of the allograft. Fourth, in addition
      to T(reg) depletion, costimulation of the tolerant alloreactive T cells or
      activation of the APC compartment also reverted alloreactive T cell tolerance and
      restored an activated phenotype. Finally, it is shown that the suppression is
      long-lived, and in the absence of anti-CD154 and donor-specific transfusion,
      these T(reg) can chronically suppress effector cell responses, allowing long
      lived graft acceptance.

PMID- 16002674
TI  - Mechanisms of gene therapy for tolerance: B7 signaling is required for peptide
      IgG gene-transferred tolerance induction.
AB  - LPS-activated B cells, transduced with IgG fusion proteins, are highly
      tolerogenic APCs. To analyze the mechanisms for this B cell-delivered gene
      therapy, we first followed the fate of CFSE-labeled B cell blasts. These cells
      primarily localized to the spleen, where a small population persisted for at
      least 1 mo after injection. By day 7 after injection, approximately 95% of the
      transduced cells had divided at least once, presumably an effect of the in vitro
      LPS activation into the cycle, because resting cells did not divide. B cells from
      gld donors were not tolerogenic, initially suggesting a role for Fas ligand
      (FasL) in tolerance. Because transduced normal B cells expressed only low levels
      of FasL and did not kill Fas-expressing Jurkat or A20 B lymphoma cells in vitro,
      these data suggest that gld B cells are not tolerogenic due to unique
      characteristics of these B cells rather than the lack of functional FasL
      expression. The transduced B cell blasts displayed significant up-regulation of
      both B7 costimulatory molecules, and B7.2 up-regulation was maintained through
      day 7 in vivo. When B cells from B7 knockout donors were transduced to express Ig
      fusion proteins, they were not tolerogenic in two different mouse strains and Ag
      models. Moreover, anti-B7 Ab blocked tolerance induction in this model, a result
      consistent with a role for B7 in tolerance induction. We propose that tolerance
      may be induced in this model by B7-driven negative regulatory signaling, but
      tolerance is maintained by a lack of signal 2, because expression of B7 is
      eventually lost in vivo.

PMID- 16002675
TI  - IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17
      response during tuberculosis but is dispensable for protection and antigen
      specific IFN-gamma responses if IL-12p70 is available.
AB  - IL-12p70 induced IFN-gamma is required to control Mycobacterium tuberculosis
      growth; however, in the absence of IL-12p70, an IL-12p40-dependent pathway
      mediates induction of IFN-gamma and initial bacteriostatic activity. IL-23 is an
      IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a
      p19 subunit that is implicated in the induction of CD4 T cells associated with
      autoimmunity and inflammation. We show that in IL-23 p19-deficient mice,
      mycobacterial growth is controlled, and there is no diminution in either the
      number of IFN-gamma-producing Ag-specific CD4 T cells or local IFN-gamma mRNA
      expression. Conversely, there is an almost total loss of both IL-17-producing Ag
      specific CD4 T cells and local production of IL-17 mRNA in these mice. The
      absence of IL-17 does not alter expression of the antimycobacterial genes, NO
      synthase 2 and LRG-47, and the absence of IL-23 or IL-17, both of which are
      implicated in mediating inflammation, fails to substantially affect the
      granulomatous response to M. tuberculosis infection of the lung. Despite this
      redundancy, IL-23 is required to provide a moderate level of protection in the
      absence of IL-12p70, and this protection correlates with a requirement for IL-23
      in the IL-12p70-independent induction of Ag-specific, IFN-gamma-producing CD4 T
      cells. We also show that IL-23 is required for the induction of an IL-17
      producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of
      IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T
      cells both in vitro and in vivo.

PMID- 16002676
TI  - Cross-presentation of the long-lived lymphocytic choriomeningitis virus
      nucleoprotein does not require neosynthesis and is enhanced via heat shock
      proteins.
AB  - Many viral proteins that contain MHC class I-restricted peptides are long-lived,
      and it is elusive how they can give rise to class I epitopes. Recently, we showed
      that direct presentation of an epitope of the long-lived lymphocytic
      choriomeningitis virus nucleoprotein (LCMV-NP) required neosynthesis in
      accordance with the defective ribosomal products hypothesis. In this study, we
      report that LCMV-NP can be cross-primed in mice using either LCMV-NP-transfected
      human HEK293 or BALB/c-derived B8 cells as Ag donor cells. In addition, we
      establish that contrary to direct presentation, cross-presentation required
      accumulation of the mature LCMV-NP and could not be sustained by the newly
      synthesized LCMV-NP protein, intermediate proteasomal degradation products, or
      the minimal NP396 epitope. Nevertheless, NP cross-presentation was enhanced by
      heat shock and was blunted by inhibitors of heat shock protein 90 and gp96. We
      propose that cross-presentation has evolved to sustain the presentation of stable
      viral proteins when their neosynthesis has ceased in infected donor cells.

PMID- 16002677
TI  - Nitric oxide inhibits IFN-alpha production of human plasmacytoid dendritic cells
      partly via a guanosine 3',5'-cyclic monophosphate-dependent pathway.
AB  - NO, a free radical gas, is known to be critically involved not only in vascular
      relaxation but also in host defense. Besides direct bactericidal effects, NO has
      been shown to inhibit Th1 responses and modulate immune responses in vivo,
      although the precise mechanism is unclear. In this study, we examined the effect
      of NO on human plasmacytoid dendritic cells (pDCs) to explore the possibility
      that NO might affect innate as well as adaptive immunity through pDCs. We found
      that NO suppressed IFN-alpha production of pDCs partly via a cGMP-dependent
      mechanism, which was accompanied by down-regulation of IFN regulatory factor 7
      expression. Furthermore, treatment of pDCs with NO decreased production of IL-6
      and TNF-alpha and up-regulated OX40 ligand expression. In accordance with these
      changes, pDCs treated with NO plus CpG-oligodeoxynucleotide AAC-30 promoted
      differentiation of naive CD4(+) T cells into a Th2 phenotype. Moreover, pDCs did
      not express inducible NO synthase even after treatment with AAC-30, LPS, and
      several cytokines. These results suggest that exogenous NO and its second
      messenger, cGMP, alter innate as well as adaptive immune response through
      modulating the functions of pDCs and may be involved in the pathogenesis of
      certain Th2-dominant allergic diseases.

PMID- 16002678
TI  - Cyclooxygenase 2 inhibition promotes IFN-gamma-dependent enhancement of antitumor
      responses.
AB  - In previous studies, we demonstrated an immune suppressive network in non-small
      cell lung cancer that is due to overexpression of tumor cyclooxygenase 2 (COX-2).
      In this study, we assessed the vaccination response to tumor challenge following
      either pharmacological or genetic inhibition of COX-2 in a murine lung cancer
      model. Treatment of naive mice with the COX-2 inhibitor, SC-58236, skewed
      splenocytes toward a type 1 cytokine response, inducing IFN-gamma, IL-12, and IFN
      gamma-inducible protein 10, whereas the type 2 cytokines IL-4, IL-5, and IL-10
      remained unaltered. Fifty percent of mice receiving SC-58236 and an irradiated
      tumor cell vaccine completely rejected tumors upon challenge. Those mice that did
      form tumors following challenge demonstrated a reduced tumor growth. In contrast,
      all mice either vaccinated with irradiated tumor cells alone or receiving SC
      58236 alone showed progressive tumor growth. Studies performed in CD4 and CD8
      knockout mice revealed a requirement for the CD4 T lymphocyte subset for the
      complete rejection of tumors. To determine the role of host COX-2 expression on
      the vaccination responses, studies were performed in COX-2 gene knockout mice.
      Compared with control littermates, COX-2(-/-) mice showed a significant tumor
      growth reduction, whereas heterozygous COX-2(-/+) mice had an intermediate tumor
      growth reduction following vaccination. In vivo depletion of IFN-gamma abrogated
      the COX-2 inhibitor-mediated enhancement of the vaccination effect. These
      findings provide a strong rationale for additional evaluation of the capacity of
      COX-2 inhibitors to enhance vaccination responses against cancer.

PMID- 16002679
TI  - Dendritic cell-mediated cross-presentation of antigens derived from colon
      carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine,
      oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen
      specific CTL response with antitumor activity in vitro.
AB  - Gemcitabine, oxaliplatin, leucovorin, and 5-fluorouracil (GOLF) is a novel
      multidrug regimen inducing high levels of necrosis and apoptosis in colon
      carcinoma cells. This regimen is also able to promote a process of Ag remodeling
      including up-regulation of immunotherapy targets like carcinoembryonic Ag (CEA),
      thymidylate synthase (TS). We have conducted a preclinical study aimed to
      investigate whether these drug-induced modifications would also enhance colon
      cancer cell immunogenicity. Several CTL lines were thus generated by in vitro
      stimulating human HLA-A(*)02.01(+) PBMCs, from normal donors and colon cancer
      patients, with autologous dendritic cells cross-primed with cell lysates of colon
      cancer cells untreated, irradiated, or previously exposed to different drug
      treatments including the GOLF regimen. Class I HLA-restricted cytolytic activity
      of these CTL lines was tested against colon cancer cells and CEA and TS gene
      transfected target cells. These experiments revealed that CTLs sensitized with
      GOLF-treated cancer cells were much more effective than those sensitized with the
      untreated colon carcinoma cells or those exposed to the other treatments. CTL
      lines sensitized against the GOLF-treated colon cancer cells, also expressed a
      greater percentage of T-lymphocyte precursors able to recognize TS- and CEA
      derived peptides. These results suggest that GOLF regimen is a powerful antitumor
      and immunomodulating regimen that can make the tumor cells a suitable means to
      induce an Ag-specific CTL response. These results suggest that a rationale
      combination of GOLF chemotherapy with cytokine-based immunotherapy could generate
      a chemotherapy-modulated Ag-specific T-lymphocyte response in cancer patients
      able to destroy the residual disease survived to the cytotoxic drugs.

PMID- 16002680
TI  - Orally tolerized T cells can form conjugates with APCs but are defective in
      immunological synapse formation.
AB  - Oral tolerance is systemic immune hyporesponsiveness induced by the oral
      administration of soluble Ags. Hyporesponsiveness of Ag-specific CD4 T cells is
      responsible for this phenomenon. However, the molecular mechanisms underlying the
      hyporesponsive state of these T cells are not fully understood. In the present
      study, we investigated the ability of orally tolerized T cells to form conjugates
      with Ag-bearing APCs and to translocate TCR, protein kinase C-theta (PKC-theta),
      and lipid rafts into the interface between T cells and APCs. Orally tolerized T
      cells were prepared from the spleens of OVA-fed DO11.10 mice. Interestingly, the
      orally tolerized T cells did not show any impairment in the formation of
      conjugates with APCs. The conjugates were formed in a LFA-1-dependent manner.
      Upon antigenic stimulation, the tolerized T cells could indeed activate Rap1,
      which is critical for LFA-1 activation and thus cell adhesion. However, orally
      tolerized T cells showed defects in the translocation of TCR, PKC-theta, and
      lipid rafts into the interface between T cells and APCs. Translocation of TCR and
      PKC-theta to lipid raft fractions upon antigenic stimulation was also impaired in
      the tolerized T cells. Ag-induced activation of Vav, Rac1, and cdc42, which are
      essential for immunological synapse and raft aggregation, were down-regulated in
      orally tolerized T cells. These results demonstrate that orally tolerized T cells
      can respond to specific Ags in terms of conjugate formation but not with
      appropriate immunological synapse formation. This may account for the
      hyporesponsive state of orally tolerized T cells.

PMID- 16002681
TI  - TLR4 and Toll-IL-1 receptor domain-containing adapter-inducing IFN-beta, but not
      MyD88, regulate Escherichia coli-induced dendritic cell maturation and apoptosis
      in vivo.
AB  - Dendritic cells (DC) are short-lived, professional APCs that play a central role
      in the generation of adaptive immune responses. Induction of efficient immune
      responses is dependent on how long DCs survive in the host. Therefore, the
      regulation of DC apoptosis in vivo during infection remains an important question
      that requires further investigation. The impact of Escherichia coli bacteremia on
      DCs has never been analyzed. We show here that i.v. or i.p. administration of
      live or heat-killed E. coli in mice induces splenic DC migration, maturation, and
      apoptosis. We further characterize which TLR and Toll-IL-1R (TIR)-containing
      adaptor molecules regulate these processes in vivo. In this model, DC maturation
      is impaired in TLR2(-/-), TLR4(-/-) and TIR domain-containing adapter-inducing
      IFN-beta (TRIF)(-/-) mice. In contrast, DC apoptosis is reduced only in TLR4(-/-)
      and TRIF(-/-) mice. As expected, DC apoptosis induced by the TLR4 ligand LPS is
      also abolished in these mice. Injection of the TLR9 ligand CpG
      oligodeoxynucleotide (synthetic bacterial DNA) induces DC migration and
      maturation, but only modest DC apoptosis when compared with LPS and E. coli.
      Together, these results suggest that E. coli bacteremia directly impacts on DC
      maturation and survival in vivo through a TLR4-TRIF-dependent signaling pathway.

PMID- 16002682
TI  - Enhanced antibacterial potential in UBP43-deficient mice against Salmonella
      typhimurium infection by up-regulating type I IFN signaling.
AB  - ISG15 is an IFN-inducible ubiquitin-like protein and its expression and
      conjugation to target proteins are dramatically induced upon viral or bacterial
      infection. We have generated a UBP43 knockout mouse model that is lacking an
      ISG15-specific isopeptidase to study the biological role of the protein
      ISGylation system. We report that UBP43-deficient mice are hypersensitive to LPS
      induced lethality and that TIR domain-containing adapter inducing IFN-beta -->
      IFN regulatory factor 3 --> type I IFN is the major axis to induce protein
      ISGylation and UBP43 expression in macrophages upon LPS treatment. In ubp43(-/-)
      macrophages, upon LPS treatment we detected increased expression of IFN
      stimulated genes, including genes for several cytokines and chemokines involved
      in the innate immune response. The ubp43(-/-) mice were able to restrict the
      growth of Salmonella typhimurium more efficiently than wild-type mice. These
      results clearly demonstrate two aspects of IFN-signaling, a beneficial effect
      against pathogens but a detriment to the body without strict control.

PMID- 16002683
TI  - Antigen presentation by an immature myeloid dendritic cell line does not cause
      CTL deletion in vivo, but generates CD8+ central memory-like T cells that can be
      rescued for full effector function.
AB  - Immature dendritic cells (DC), in contrast to their mature counterparts, are
      incapable of mobilizing a CD8+ CTL response, and, instead, have been reported to
      induce CTL tolerance. We directly addressed the impact of immature vs mature DC
      on CTL responses by infusing adenovirus peptide-loaded DC (of the D1 cell line)
      into mice that had received adenovirus-specific naive TCR-transgenic CD8+ T
      cells. Whereas i.v. injection of mature DC triggered vigorous CTL expansion,
      immature DC elicited little proliferation involving only a minority of the TCR
      transgenic CTL. Even though the latter CTL developed effector functions,
      including cytolytic activity and proinflammatory cytokine secretion, these cells
      differed significantly from CTL primed by mature DC in that they did not exhibit
      down-regulation of CD62L and CCR7, receptors involved in trapping of T cells in
      the lymphoid organs. Interestingly, adoptive transfer of CTL effector cells
      harvested after priming by either mature or immature DC into naive recipient
      mice, followed by exposure to adenovirus, yielded quantitatively and
      qualitatively indistinguishable CTL memory responses. Therefore, in vivo priming
      of naive CD8+ T cells by immature DC, although failing to induce a full-blown,
      systemic CTL response, resulted in the formation of central memory-like T cells
      that were able to expand and produce IFN-gamma upon secondary antigenic
      stimulation.

PMID- 16002684
TI  - T cell leukemia-1 modulates TCR signal strength and IFN-gamma levels through
      phosphatidylinositol 3-kinase and protein kinase C pathway activation.
AB  - A signaling role for T cell leukemia-1 (TCL1) during T cell development or in
      premalignant T cell expansions and mature T cell tumors is unknown. In this
      study, TCL1 is shown to regulate the growth and survival of peripheral T cells
      but not precursor thymocytes. Proliferation is increased by TCL1-induced lowering
      of the TCR threshold for CD4(+) and CD8(+) T cell activation through both PI3K
      Akt and protein kinase C-MAPK-ERK signaling pathways. This effect is submaximal
      as CD28 costimulation coupled to TCL1 expression additively accelerates dose
      dependent T cell growth. In addition to its role in T cell proliferation, TCL1
      also increases IFN-gamma levels from Th1-differentiated T cells, an effect that
      may provide a survival advantage during premalignant T cell expansions and in
      clonal T cell tumors. Combined, these data indicate a role for TCL1 control of
      growth and effector T cell functions, paralleling features provided by TCR-CD28
      costimulation. These results also provide a more detailed mechanism for TCL1
      augmented signaling and help explain the delayed occurrence of mature T cell
      expansions and leukemias despite tumorigenic TCL1 dysregulation that begins in
      early thymocytes.

PMID- 16002685
TI  - CCR2 and CCR6, but not endothelial selectins, mediate the accumulation of
      immature dendritic cells within the lungs of mice in response to particulate
      antigen.
AB  - Dendritic cells (DC) migrate from sites of inflammation to lymph nodes to
      initiate primary immune responses, but the molecular mechanisms by which DC are
      replenished in the lungs during ongoing pulmonary inflammation are unknown. To
      address this question, we analyzed the secondary pulmonary immune response of Ag
      primed mice to intratracheal challenge with the particulate T cell-dependent Ag
      sheep erythrocytes (SRBC). We studied wild-type C57BL/6 mice and syngeneic gene
      targeted mice lacking either both endothelial selectins (CD62E and CD62P), or the
      chemokine receptors CCR2 or CCR6. DC, defined as non-autofluorescent, MHC class
      II(+)CD11c(mod) cells, were detected in blood, enzyme-digested minced lung, and
      bronchoalveolar lavage fluid using flow cytometry and immunohistology. Compared
      with control mice, Ag challenge increased the frequency and absolute numbers of
      DC, peaking at day 1 in peripheral blood (6.5-fold increase in frequency), day 3
      in lung mince (20-fold increase in total DC), and day 4 in bronchoalveolar lavage
      fluid (55-fold increase in total DC). Most lung DC expressed CD11c, CD11b, and
      low levels of MHC class II, CD40, CD80, and CD86, consistent with an immature
      myeloid phenotype. DC accumulation depended in part upon CCR2 and CCR6, but not
      endothelial selectins. Thus, during lung inflammation, immature myeloid DC from
      the bloodstream replace emigrating immature DC and transiently increase total
      intrapulmonary APC numbers. Early DC recruitment depends in part on CCR2 to
      traverse vascular endothelium, plus CCR6 to traverse alveolar epithelium. The
      recruitment of circulating immature DC represents a potential therapeutic step at
      which to modulate immunological lung diseases.

PMID- 16002686
TI  - Regulation of follicular dendritic cell networks by activated T cells: the role
      of CD137 signaling.
AB  - B cells, but not T cells, are considered to be important for the formation of
      follicular dendritic cell (FDC) clusters. Stimulation with agonist mAbs against
      CD137 (4-1BB), a TNFR family member primarily expressed on activated T cells, was
      effective in promoting T cell responses, but paradoxically suppressed T-dependent
      humoral immunity and autoantibody production in autoimmune disease models. Our
      present study shows that agonistic anti-CD137 treatment activates T cells,
      resulting in diminished FDC networks in B cell follicles, which are important
      components in T-dependent humoral immune responses both before and after the
      initiation of an immune response. Pretreatment with anti-CD137 before the
      secondary immunization inhibited memory Ab responses. Interestingly, CD137
      costimulation-induced diminishment of FDC is T cell dependent. In addition, both
      CD4(+) and CD8(+) T cells are recruited into FDC area and are able to regulate
      FDCs by CD137 costimulation through a direct or indirect mechanism. These studies
      have revealed a previously unappreciated role of T cells in the regulation of FDC
      networks.

PMID- 16002687
TI  - Dendritic cell aggresome-like-induced structure formation and delayed antigen
      presentation coincide in influenza virus-infected dendritic cells.
AB  - Influenza virus infection induces maturation of murine dendritic cells (DCs),
      which is most important for the initiation of an immune response. However, in
      contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of
      up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC
      class I molecules as well as costimulatory molecules on the cell surface and the
      accumulation of newly synthesized ubiquitinated proteins in large cytosolic
      structures, called DC aggresome-like-induced structures (DALIS). These structures
      were observed previously after LPS-induced maturation of DCs, and it was
      speculated that they play a role in the regulation of MHC class I Ag
      presentation. Our findings provide the first evidence for a connection between DC
      maturation, MHC class I-restricted Ag presentation, and DALIS formation, which is
      further supported by the observation that DALIS contain ubiquitinated influenza
      nucleoprotein.

PMID- 16002688
TI  - NKT cells are critical for the initiation of an inflammatory bowel response
      against Toxoplasma gondii.
AB  - We demonstrated in this study the critical role of NKT cells in the lethal
      ileitis induced in C57BL/6 mice after infection with Toxoplasma gondii. This
      intestinal inflammation is caused by overproduction of IFN-gamma in the lamina
      propria. The implication of NKT cells was confirmed by the observation that NKT
      cell-deficient mice (Jalpha281(-/-)) are more resistant than C57BL/6 mice to the
      development of lethal ileitis. Jalpha281(-/-) mice failed to overexpress IFN
      gamma in the intestine early after infection. This detrimental effect of NKT
      cells is blocked by treatment with alpha-galactosylceramide, which prevents death
      in C57BL/6, but not in Jalpha281(-/-), mice. This protective effect is
      characterized by a shift in cytokine production by NKT cells toward a Th2 profile
      and correlates with an increased number of mesenteric Foxp3 lymphocytes. Using
      chimeric mice in which only NKT cells are deficient in the IL-10 gene and mice
      treated with anti-CD25 mAb, we identified regulatory T cells as the source of the
      IL-10 required for manifestation of the protective effect of alpha
      galactosylceramide treatment. Our results highlight the participation of NKT
      cells in the parasite clearance by shifting the cytokine profile toward a Th1
      pattern and simultaneously to immunopathological manifestation when this Th1
      immune response remains uncontrolled.

PMID- 16002689
TI  - In vivo assessment of the relative contributions of deletion, anergy, and editing
      to B cell self-tolerance.
AB  - In normal B cell development, a large percentage of newly formed cells bear
      receptors with high levels of self-reactivity that must be tolerized before entry
      into the mature B cell pool. We followed the fate of self-reactive B cells
      expressing high affinity anti-hen egg lysozyme (HEL) Ag receptors exposed in vivo
      to membrane HEL in a setting in which the anti-HEL L chain was "knocked-in" at
      the endogenous L chain locus. These mice demonstrated extensive and efficient L
      chain receptor editing responses and had B cell numbers comparable to those found
      in animals lacking membrane Ag. BrdU labeling indicated that the time required
      for editing in response to membrane HEL was approximately 6 h. In mice transgenic
      for soluble HEL, anti-HEL B cells capable of editing showed evidence for both
      editing and anergy. These data identify receptor editing as a major physiologic
      mechanism by which highly self-reactive B cells are tolerized to membrane and
      soluble self-Ags.

PMID- 16002690
TI  - IL-4 inhibits bone-resorbing activity of mature osteoclasts by affecting NF-kappa
      B and Ca2+ signaling.
AB  - IL-4 is an important immune cytokine that regulates bone homeostasis. We
      investigated the molecular mechanism of IL-4 action on bone-resorbing mature
      osteoclasts. Using a highly purified population of mature osteoclasts, we show
      that IL-4 dose-dependently inhibits receptor activator of NF-kappaB ligand
      (RANKL)-induced bone resorption by mature osteoclasts. We detected the existence
      of IL-4R mRNA in mature osteoclasts. IL-4 decreases TRAP expression without
      affecting multinuclearity of osteoclasts, and inhibits actin ring formation and
      migration of osteoclasts. Interestingly, IL-4 inhibition of bone resorption
      occurs through prevention of RANKL-induced nuclear translocation of p65 NF-kappaB
      subunit, and intracellular Ca(2+) changes. Moreover, IL-4 rapidly decreases RANKL
      stimulated ionized Ca(2+) levels in the blood, and mature osteoclasts in IL-4
      knockout mice are sensitive to RANKL action to induce bone resorption and
      hypercalcemia. Furthermore, IL-4 inhibits bone resorption and actin ring
      formation by human mature osteoclasts. Thus, we reveal that IL-4 acts directly on
      mature osteoclasts and inhibits bone resorption by inhibiting NF-kappaB and
      Ca(2+) signaling.

PMID- 16002691
TI  - Regulation of LFA-1 activity through cytoskeleton remodeling and signaling
      components modulates the efficiency of HIV type-1 entry in activated CD4+ T
      lymphocytes.
AB  - Besides interactions between the viral envelope glycoproteins with cell surface
      receptors, interactions between cell-derived molecules incorporated onto virions
      and their ligand could also modulate HIV type-1 (HIV-1) entry inside CD4(+) T
      lymphocytes. Although incorporation of host ICAM-1 within HIV-1 increases both
      virus attachment and fusion, the precise mechanism through which this phenomenon
      is occurring is still unclear. We demonstrate in this study that activation of
      primary human CD4(+) T lymphocytes increases LFA-1 affinity and avidity states,
      two events promoting the early events of the HIV-1 replication cycle through
      interactions between virus-embedded host ICAM-1 and LFA-1 clusters. Confocal
      analyses suggest that HIV-1 is concentrated in microdomains rich in LFA-1
      clusters that also contain CD4 and CXCR4 molecules. Experiments performed with
      specific inhibitors revealed that entry of HIV-1 in activated CD4(+) T cells is
      regulated by LFA-1-dependent ZAP70, phospholipase Cgamma1, and calpain enzymatic
      activities. By using laboratory and clinical strains of HIV-1 produced in primary
      human cells, we demonstrate the importance of the LFA-1 activation state and
      cluster formation in the initial step of the virus life cycle. Overall, these
      data provide new insights into the complex molecular events involved in HIV-1
      binding and entry.

PMID- 16002692
TI  - Genetic dissection of the murine lupus susceptibility locus Sle2: contributions
      to increased peritoneal B-1a cells and lupus nephritis map to different loci.
AB  - Lupus pathogenesis in the NZM2410 mouse model results from the expression of
      multiple interacting susceptibility loci. Sle2 on chromosome 4 was significantly
      linked to glomerulonephritis in a linkage analysis of a NZM2410 x B6 cross. Yet,
      Sle2 expression alone on a C57BL/6 background did not result in any clinical
      manifestation, but in an abnormal B cell development, including the accumulation
      of B-1a cells in the peritoneal cavity and spleen. Analysis of B6.Sle2 congenic
      recombinants showed that at least three independent loci, New Zealand White
      derived Sle2a and Sle2b, and New Zealand Black-derived Sle2c, contribute to an
      elevated number of B-1a cells, with Sle2c contribution being the strongest of the
      three. To determine the contribution of these three Sle2 loci to lupus
      pathogenesis, we used a mapping by genetic interaction strategy, in which we bred
      them to B6.Sle1.Sle3 mice. We then compared the phenotypes of these triple
      congenic mice with that of previously characterized B6.Sle1.Sle2.Sle3, which
      express the entire Sle2 interval in combination with Sle1 and Sle3. Sle2a and
      Sle2b, but not Sle2c, contributed significantly to lupus pathogenesis in terms of
      survival rate, lymphocytic expansion, and kidney pathology. These results show
      that the Sle2 locus contains several loci affecting B cell development, with only
      the two NZW-derived loci having the least effect of B-1a cell accumulation
      significantly contributing to lupus pathogenesis.

PMID- 16002693
TI  - Failure of CD25+ T cells from lupus-prone mice to suppress lupus
      glomerulonephritis and sialoadenitis.
AB  - The development of organ-specific autoimmune diseases in mice thymectomized on
      day 3 of life (d3tx mice) can be prevented by transferring CD4(+)CD25(+) T cells
      from syngeneic, normal adult mice. Using a d3tx model, we asked whether
      CD4(+)CD25(+) T cell deficiency contributes to glomerulonephritis (GN) in lupus
      prone mice. New Zealand Mixed 2328 (NZM2328) mice spontaneously develop
      autoantibodies to dsDNA and female-dominant, fatal GN. After d3tx, both male and
      female NZM2328 mice developed 1) accelerated dsDNA autoantibody response, 2)
      early onset and severe proliferative GN with massive mesangial immune complexes,
      and 3) autoimmune disease of the thyroid, lacrimal gland, and salivary gland. The
      d3tx male mice also developed autoimmune prostatitis. The transfer of CD25(+)
      cells from 6-wk-old asymptomatic NZM2328 donors effectively suppressed dsDNA
      autoantibody and the development of autoimmune diseases, with the exception of
      proliferative lupus GN and sialoadenitis. This finding indicates that NZM2328
      lupus mice have a selective deficiency in T cells that regulates the development
      of lupus GN and sialoadenitis. After d3tx, the proliferative GN of female mice
      progressed to fatal GN, but largely regressed in the male, thereby revealing a
      checkpoint in lupus GN progression that depends on gender.

PMID- 16002694
TI  - Restraint of B cell activation by Foxj1-mediated antagonism of NF-kappa B and IL
      6.
AB  - The forkhead transcription factor Foxj1 inhibits spontaneous autoimmunity, in
      part by antagonizing NF-kappaB activation in T cells. We demonstrate here that
      Foxj1 also inhibits humoral immune responses intrinsically in B cells; Foxj1
      deficiency in B cells results in spontaneous and accentuated germinal center
      formation, associated with the development of pathogenic autoantibodies and
      accentuated responses to immunizations-all reflecting excessive activity of NF
      kappaB and its target gene IL-6, and correlating with a requirement for Foxj1 to
      regulate the inhibitory NF-kappaB component IkappaBbeta. Thus, Foxj1 restrains B
      cell activation and the maturation of humoral responses, demonstrating a critical
      role for at least this forkhead transcription factor in the regulation of B
      lymphocyte homeostasis.

PMID- 16002695
TI  - Lipopolysaccharide injection induces relapses of experimental autoimmune
      encephalomyelitis in nontransgenic mice via bystander activation of autoreactive
      CD4+ cells.
AB  - Infections sometimes associate with exacerbations of autoimmune diseases through
      pathways that are poorly understood. Ag-specific mechanisms such as cross
      reactivity between a microbial Ag and a self-Ag have received no direct support.
      In this study, we show that injection of LPS induces experimental autoimmune
      encephalomyelitis in TCR-transgenic mice and relapse of encephalomyelitis in
      normal mice. This form of treatment induces proliferation and cytokine production
      in a fraction of effector/memory Th lymphocytes in vitro via physical contact of
      Th cells with CD4(-) LPS-responsive cells. TCR-mediated signals are not
      necessary; rather what is required is ligation of costimulatory receptors on Th
      cells by costimulatory molecules on the CD4(-) cells. This form of bystander
      activation provides an Ag-independent link between infection and autoimmunity
      that might fit the clinical and epidemiological data on the connection between
      infection and autoimmunity better than the Ag-specific models.

PMID- 16002696
TI  - Calnexin and ERp57 facilitate the assembly of the neonatal Fc receptor for IgG
      with beta 2-microglobulin in the endoplasmic reticulum.
AB  - The neonatal FcR (FcRn) consists of an MHC class I-like H chain in noncovalent
      association with beta(2)-microglobulin (beta(2)m). The proper folding of FcRn in
      the endoplasmic reticulum is essential for FcRn function. Using a low stringency
      immunoprecipitation of human FcRn, we observed the coprecipitation of an 88-kDa
      band. Mass spectrometry analysis revealed that this band was identical with
      calnexin (CNX). This association was verified by Western blotting the CNX or FcRn
      immunoprecipitates with either an anti-FcRn or anti-CNX Ab. In the beta(2)m-null
      FO-1 cell transfected with FcRn H chain alone or both FcRn H chain and beta(2)m,
      CNX bound to the FcRn H chain before the FcRn H chain association with beta(2)m.
      However, calreticulin only bound to the FcRn H chain-beta(2)m complex.
      Furthermore, the thiol oxidoreductase ERp57 was detected in FcRn-CNX complexes,
      suggesting its role in disulfide bond formation of the FcRn H chain. Removal of
      the N-linked glycosylation site from the FcRn H chain resulted in a decreased
      association of the FcRn H chain for beta(2)m. However, the absence of CNX did not
      significantly affect FcRn assembly as defined by the ability of FcRn to bind IgG
      and exit to the cell surface. This suggests that other chaperones compensate for
      the function of CNX in FcRn assembly. In addition, we found that tapasin and TAP
      were not involved in FcRn assembly, as shown by coimmunoprecipitation in THP-1
      cells and IgG-binding assays in 721.220 (tapasin-deficient) and 721.174 (TAP
      deficient) cells transfected with FcRn. These findings show the importance of
      chaperones in FcRn assembly.

PMID- 16002697
TI  - Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a
      molecular basis for NKT cell activation.
AB  - NKT cells are immunoregulatory lymphocytes whose activation is triggered by the
      recognition of lipid Ags in the context of the CD1d molecules by the TCR. In this
      study we present the crystal structure to 2.8 A of mouse CD1d bound to
      phosphatidylcholine. The interactions between the ligand acyl chains and the CD1d
      molecule define the structural and chemical requirements for the binding of lipid
      Ags to CD1d. The orientation of the polar headgroup toward the C terminus of the
      alpha1 helix provides a rationale for the structural basis for the observed
      Valpha chain bias in invariant NKT cells. The contribution of the ligand to the
      protein surface suggests a likely mode of recognition of lipid Ags by the NKT
      cell TCR.

PMID- 16002698
TI  - Effects of Bcl-2 levels on Fas signaling-induced caspase-3 activation: molecular
      genetic tests of computational model predictions.
AB  - Fas-induced apoptosis is a critical process for normal immune system development
      and function. Although many molecular components in the Fas signaling pathway
      have been identified, a systematic understanding of how they work together to
      determine network dynamics and apoptosis itself has remained elusive. To address
      this, we generated a computational model for interpreting and predicting effects
      of pathway component properties. The model integrates current information
      concerning the signaling network downstream of Fas activation, through both type
      I and type II pathways, until activation of caspase-3. Unknown parameter values
      in the model were estimated using experimental data obtained from human Jurkat T
      cells. To elucidate critical signaling network properties, we examined the
      effects of altering the level of Bcl-2 on the kinetics of caspase-3 activation,
      using both overexpression and knockdown in the model and experimentally.
      Overexpression was used to distinguish among alternative hypotheses for
      inhibitory binding interactions of Bcl-2 with various components in the
      mitochondrial pathway. In comparing model simulations with experimental results,
      we find the best agreement when Bcl-2 blocks the release of cytochrome c by
      binding to both Bax and truncated Bid instead of Bax, truncated Bid, or Bid
      alone. Moreover, although Bcl-2 overexpression strongly reduces caspase-3
      activation, Bcl-2 knockdown has a negligible effect, demonstrating a general
      model finding that varying the expression levels of signal molecules frequently
      has asymmetric effects on the outcome. Finally, we demonstrate that the relative
      dominance of type I vs type II pathways can be switched by varying particular
      signaling component levels without changing network structure.

PMID- 16002699
TI  - Hierarchical regulation of CTLA-4 dimer-based lattice formation and its
      biological relevance for T cell inactivation.
AB  - CTLA-4 is an activation-induced, homodimeric inhibitory receptor in T cells.
      Recent crystallographic reports have suggested that it may form lattice-like
      arrays on the cell surface upon binding B7.1/B7.2 (CD80, CD86) molecules. To test
      the biological relevance of these CTLA-4-B7 lattices, we introduced a C122A point
      mutation in human CTLA-4, because this residue was shown to be essential for
      dimerization in solution. Surprisingly, we found that up to 35% of C122A CTLA-4
      dimerized in human T lymphocytes. Moreover, C122A CTLA-4 partitioned within lipid
      rafts, colocalized with the TCR in the immunological synapse, and inhibited T
      cell activation. C122-independent dimerization of CTLA-4 involved N
      glycosylation, because further mutation of the N78 and N110 glycosylation sites
      abrogated dimerization. Despite being monomeric, the N78A/N110A/C122A triple
      mutant CTLA-4 localized in the immunological synapse and inhibited T cell
      activation. Such functionality correlated with B7-induced dimerization of these
      mutant molecules. Based on these data, we propose a model of hierarchical
      regulation of CTLA-4 oligomerization by which B7 binding ultimately determines
      the formation of dimer-dependent CTLA-4 lattices that may be necessary for
      triggering B7-dependent T cell inactivation.

PMID- 16002700
TI  - Mutational analysis of the human 2B4 (CD244)/CD48 interaction: Lys68 and Glu70 in
      the V domain of 2B4 are critical for CD48 binding and functional activation of NK
      cells.
AB  - Interaction between receptors and ligands plays a critical role in the generation
      of immune responses. The 2B4 (CD244), a member of the CD2 subset of the Ig
      superfamily, is the high affinity ligand for CD48. It is expressed on NK cells, T
      cells, monocytes, and basophils. Recent data indicate that 2B4/CD48 interactions
      regulate NK and T lymphocyte functions. In human NK cells, 2B4/CD48 interaction
      induces activation signals, whereas in murine NK cells it sends inhibitory
      signals. To determine the structural basis for 2B4/CD48 interaction, selected
      amino acid residues in the V domain of the human 2B4 (h2B4) were mutated to
      alanine by site-directed mutagenesis. Following transient expression of these
      mutants in B16F10 melanoma cells, their interaction with soluble CD48-Fc fusion
      protein was assessed by flow cytometry. We identified amino acid residues in the
      extracellular domain of h2B4 that are involved in interacting with CD48. Binding
      of CD48-Fc fusion protein to RNK-16 cells stably transfected with wild-type and a
      double-mutant Lys(68)Ala-Glu(70)Ala h2B4 further demonstrated that Lys(68) and
      Glu(70) in the V domain of h2B4 are essential for 2B4/CD48 interaction.
      Functional analysis indicated that Lys(68) and Glu(70) in the extracellular
      domain of h2B4 play a key role in the activation of human NK cells through
      2B4/CD48 interaction.

PMID- 16002701
TI  - Critical role of the fifth domain of E-cadherin for heterophilic adhesion with
      alpha E beta 7, but not for homophilic adhesion.
AB  - The integrin alpha(E)beta(7) is expressed on intestinal intraepithelial T
      lymphocytes and CD8(+) T lymphocytes in inflammatory lesions near epithelial
      cells. Adhesion between alpha(E)beta(7)(+) T and epithelial cells is mediated by
      the adhesive interaction of alpha(E)beta(7) and E-cadherin; this interaction
      plays a key role in the damage of target epithelia. To explore the structure
      function relationship of the heterophilic adhesive interaction between E-cadherin
      and alpha(E)beta(7), we performed cell aggregation assays using L cells
      transfected with an extracellular domain-deletion mutant of E-cadherin. In
      homophilic adhesion assays, L cells transfected with wild-type or a domain 5
      deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-,
      or 4-deficient mutants did not. These results indicate that not only domain 1,
      but domains 2, 3, and 4 are involved in homophilic adhesion. When
      alpha(E)beta(7)(+) K562 cells were incubated with L cells expressing the wild
      type, 23% of the resulting cell aggregates consisted of alpha(E)beta(7)(+) K562
      cells. In contrast, the binding of alpha(E)beta(7)(+) K562 cells to L cells
      expressing a domain 5-deficient mutant was significantly decreased, with
      alpha(E)beta(7)(+) K562 cells accounting for only 4% of the cell aggregates,
      while homophilic adhesion was completely preserved. These results suggest that
      domain 5 is involved in heterophilic adhesion with alpha(E)beta(7), but not in
      homophilic adhesion, leading to the hypothesis that the fifth domain of E
      cadherin may play a critical role in the regulation of heterophilic adhesion to
      alpha(E)beta(7) and may be a potential target for treatments altering the
      adhesion of alpha(E)beta(7)(+) T cells to epithelial cells in inflammatory
      epithelial diseases.

PMID- 16002702
TI  - Transcriptional regulation of CD1D1 by Ets family transcription factors.
AB  - CD1 molecules are MHC class I-like glycoproteins specialized in presenting
      lipid/glycolipid Ags to T cells. The distinct cell-type specific expression of
      CD1D1 plays an important role in the development and function of NKT cells, a
      unique subset of immunoregulatory T cells. However, the mechanisms regulating
      CD1D1 expression are largely unknown. In this study, we have characterized the
      upstream region of the CD1D1 gene and identified a minimal promoter region within
      200 bp from the translational start site of CD1D1 that exhibits cell-type
      specific promoter activity. Analysis of this region revealed an Ets binding site
      critical for CD1D1 promoter activity. Gel shift assays and chromatin
      immunoprecipitation experiments showed that Elf-1 and PU.1 bind to the CD1D1
      promoter. Furthermore, we found that gene disruption of Elf-1 resulted in
      decreased CD1D1 expression on B cells but not other cell types, whereas
      conditional activation of PU.1 negatively regulated CD1D1 expression in PU.1
      deficient myeloid cells. These findings are the first to demonstrate that Ets
      proteins are involved in the transcriptional regulation of CD1D1 and that they
      may function uniquely in different cell types.

PMID- 16002703
TI  - X box-like sequences in the MHC class II region maintain regulatory function.
AB  - Sequences homologous to the canonical MHC class II (MHC-II) gene X box regulatory
      elements were identified within the HLA-DR subregion of the human MHC and termed
      X box-like (XL) sequences. Several XL box sequences were found to bind the MHC
      class II-specific transcription factors regulatory factor X and CIITA and were
      transcriptionally active. The histone code associated with the XL boxes and that
      of the HLA-DRA X box was determined. Using CIITA-positive and -negative B cell
      lines, CIITA-specific histone modifications were identified and found to be
      consistent among the active XL boxes. Although a remarkable similarity was
      observed for most modifications, differences in magnitude between the HLA-DRA
      promoter for modifications associated with the assembly of the general
      transcription factors, such as histone H3 lysine 9 acetylation and H3 lysine 4
      trimethylation, distinguished the very active HLA-DRA promoter from the XL box
      regions. In response to IFN-gamma, XL box-containing histones displayed increased
      acetylation, coincident with CIITA expression and that observed in B cells,
      suggesting that the end point mechanisms of chromatin remodeling for cell type
      specific MHC-II expression were similar. Lastly, an interaction between one XL
      box and the HLA-DRA promoter was observed in a chromatin-looping assay.
      Therefore, these data provide evidence that certain XL box sequences contribute
      to a global increase in chromatin accessibility of the HLA-DR region in B
      lymphocytes and in response to IFN-gamma and supports the involvement of these XL
      sequences in the regulation of MHC-II genes.

PMID- 16002704
TI  - Identification of a macrophage-specific chromatin signature in the IL-10 locus.
AB  - The molecular mechanisms that regulate expression of the immunosuppressive
      cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity
      to DNase I digestion, we show that production of IL-10 by primary mouse bone
      marrow-derived macrophages stimulated through pattern recognition receptors was
      associated with chromatin remodeling of the IL-10 locus. We also demonstrate that
      the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory
      T cells that have been differentiated in vitro. Strikingly, a novel DNase I
      hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not
      in T cells. We show that hyperacetylated histones were recruited to this site in
      stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a
      putative NF-kappaB binding site. In support of a function for this site, NF
      kappaB p65/RelA was recruited to HSS-4.5 in vivo and its activation was required
      for optimal IL-10 gene expression in LPS-stimulated macrophages.

PMID- 16002705
TI  - Hepatocytes express abundant surface class I MHC and efficiently use transporter
      associated with antigen processing, tapasin, and low molecular weight polypeptide
      proteasome subunit components of antigen processing and presentation pathway.
AB  - Hepatic expression levels of class I MHC Ags are generally regarded as very low.
      Because the status of these Ags and their ability to present peptides are
      important for the understanding of pathogen clearance and tolerogenic properties
      of the liver, we set out to identify the factors contributing to the reported
      phenotype. Unexpectedly, we found that the surface densities of K(b) and D(b) on
      C57BL/6 mouse hepatocytes are nearly as high as on splenocytes, as are the lysate
      concentrations of mRNA encoding H chain and beta(2)-microglobulin (beta(2)m). In
      contrast, the components of the peptide-loading pathway are reduced in
      hepatocytes. Despite the difference in the stoichiometric ratios of H
      chain/beta(2)m/peptide-loading machineries, both cell types express predominantly
      thermostable class I and are critically dependent on TAP and tapasin for display
      of surface Ags. Minor differences in the expression patterns in tapasin(-/-)
      background suggest cell specificity in class I assembly. Under immunostimulatory
      conditions, such as exposure to IFN-gamma or Listeria monocytogenes, hepatocytes
      respond with a vigorous mRNA synthesis of the components of the Ag presentation
      pathway (up to 10-fold enhancement) but up-regulate H chain and beta(2)m to a
      lesser degree (<2-fold). This type of response should promote rapid influx of
      newly generated peptides into the endoplasmic reticulum and preferential
      presentation of foreign/induced Ag by hepatic class I.

PMID- 16002706
TI  - A critical role for sialylation in cryoglobulin activity of murine IgG3
      monoclonal antibodies.
AB  - Cryoprecipitating IgG3 autoantibodies have been shown to play a significant role
      in the development of murine lupus-like autoimmune syndrome. However, the
      structural basis of IgG3 cryoprecipitation still remains to be defined. In view
      of the implication of positively charged amino acid residues present in variable
      regions in IgG3 cryoglobulin activity, we explored the role of terminal sialic
      acids in oligosaccharide side chains for the cryogenic activity of IgG3 mAb.
      Comparative oligosaccharide structural analysis of different cryogenic and non
      cryogenic IgG3 mAb showed an inverse correlation between the extent of
      sialylation and cryogenic activity. The inhibitory role of sialylation was
      further confirmed by the demonstration of enrichment of less and more sialylated
      IgG3 in cryoprecipitated and noncryoprecipitated fractions, respectively,
      separated from four different cryogenic IgG3 mAb. Significantly, the sialic acid
      contents of the latter fraction became comparable to those of non-cryogenic IgG3
      mAb. Finally, we observed that highly sialylated non-cryogenic IgG3 mAb was more
      potent in the inhibition of cryoprecipitation of cryogenic IgG3 mAb. Our results
      thus suggest that the content of negatively charged sialic acids in
      oligosaccharide side chains is one of the critical factors to determine IgG3
      cryoglobulin activity, along with amino acid sequences of the IgG3 variable
      regions.

PMID- 16002707
TI  - Epistatic suppression of systemic lupus erythematosus: fine mapping of Sles1 to
      less than 1 mb.
AB  - Sle is a susceptibility locus for systemic autoimmunity derived from the lupus
      prone NZM2410 mouse. The New Zealand White-derived suppressive modifier Sles1 was
      identified as a specific modifier of Sle1 and prevents the development of IgG
      anti-chromatin autoantibodies mediated by Sle1 on the C57BL/6 (B6) background.
      Fine mapping of Sles1 with truncated congenic intervals localizes it to a
      approximately 956-kb segment of mouse chromosome 17. Sles1 completely abrogates
      the development of activated T and B cell populations in B6.Sle1. Despite this
      suppression of the Sle1-mediated cell surface activation phenotypes, B6.Sle1
      Sles1 splenic B cells still exhibit intrinsic ERK phosphorylation. Classic
      genetic complementation tests using the nonautoimmmune 129/SvJ mouse suggests
      that this strain possesses a Sles1 allele complementary to that of New Zealand
      White, as evidenced by the lack of glomerulonephritis, splenomegaly, and
      antinuclear autoantibody production seen in (129 x B6.Sle1 Sles1)F(1)s. These
      findings localize and characterize the suppressive properties of Sles1 and
      implicate 129 as a useful strain for aiding in the identification of this elusive
      epistatic modifier gene.

PMID- 16002708
TI  - Multiple germline kappa light chains generate anti-insulin B cells in nonobese
      diabetic mice.
AB  - The highly selective nature of organ-specific autoimmune disease is consistent
      with a critical role for adaptive immune responses against specific autoantigens.
      In type 1 diabetes mellitus, autoantibodies to insulin are important markers of
      the disease process in humans and nonobese diabetic (NOD) mice; however, the Ag
      specific receptors responsible for these autoantibodies are obscured by the
      polyclonal repertoire. NOD mice that harbor an anti-insulin transgene (Tg)
      (V(H)125Tg/NOD) circumvent this problem by generating a tractable population of
      insulin-binding B cells. The nucleotide structure and genetic origin of the
      endogenous kappa L chain (Vkappa or IgL) repertoire that pairs with the V(H)125Tg
      were analyzed. In contrast to oligoclonal expansion observed in systemic
      autoimmune disease models, insulin-binding B cells from V(H)125Tg/NOD mice use
      specific Vkappa genes that are clonally independent and germline encoded. When
      compared with homologous IgL genes from nonautoimmune strains, Vkappa genes from
      NOD mice are polymorphic. Analysis of the most frequently expressed Vkappa1 and
      Vkappa9 genes indicates these are shared with lupus-prone New Zealand Black/BINJ
      mice (e.g., Vkappa1-110*02 and 9-124) and suggests that NOD mice use the
      infrequent b haplotype. These findings show that a diverse repertoire of anti
      insulin B cells is part of the autoimmune process in NOD mice and structural or
      regulatory elements within the kappa locus may be shared with a systemic
      autoimmune disease.

PMID- 16002709
TI  - Several genes contribute to the production of autoreactive B and T cells in the
      murine lupus susceptibility locus Sle1c.
AB  - The systemic lupus erythematosus 1 (Sle1) locus mediates the loss of tolerance to
      nuclear Ags in the NZM2410 mouse model of lupus through intrinsic defects in both
      B and T cells. Congenic analysis has shown that Sle1 corresponds to at least
      three genetic loci, Sle1a, Sle1b, and Sle1c. Telomeric Sle1c is associated with
      abnormal B cell responses to subthreshold stimulation with anti-IgM and C3d and
      with decreased T-dependent humoral immune responses. We have proposed that these
      phenotypes resulted from polymorphisms in the C3 complement receptor Cr2 gene. We
      have also found that Sle1c was associated with the production of histone-specific
      autoreactive CD4(+) T cells, which correlated with higher activation and
      proliferative responses, and a reduction in the
      CD4(+)CD25(+)CD62L(+)forkhead/winged helix transcription factor gene (Foxp3(+))
      compartment. In this study we showed, using congenic recombinants, that the
      decreased humoral immune response and impaired GC formation map to the NZM2410
      Cr2 allele. A chronic graft-vs-host disease model also showed that Sle1c produces
      significantly more autoreactive B cells than B6 controls, and that this phenotype
      maps to two regions excluding the Cr2 gene. Mixed bone marrow chimera
      demonstrated that the increased activation, proliferative response, and reduced
      regulatory T cell compartment were intrinsic to Sle1c-expressing CD4(+) T cells.
      These phenotypes mapped to the same two loci identified with the chronic graft-vs
      host disease model, excluding the Cr2 region. Overall, these results show that
      Sle1c results in the production of autoreactive B and T cells through the
      expression of three different genes, one of which is consistent with Cr2, based
      on the phenotypes of the Cr2-deficient mice, and the other two corresponding to
      as yet unidentified genes.

PMID- 16002710
TI  - Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil
      capture and killing bacteria on airway epithelial surfaces.
AB  - Cystic fibrosis (CF) lung disease is characterized by persistent lung infection.
      Thickened (concentrated) mucus in the CF lung impairs airway mucus clearance,
      which initiates bacterial infection. However, airways have other mechanisms to
      prevent bacterial infection, including neutrophil-mediated killing. Therefore, we
      examined whether neutrophil motility and bacterial capture and killing functions
      are impaired in thickened mucus. Mucus of three concentrations, representative of
      the range of normal (1.5 and 2.5% dry weight) and CF-like thickened (6.5%) mucus,
      was obtained from well-differentiated human bronchial epithelial cultures and
      prepared for three-dimensional studies of neutrophil migration. Neutrophil
      chemotaxis in the direction of gravity was optimal in 1.5% mucus, whereas 2.5%
      mucus best supported neutrophil chemotaxis against gravity. Lateral chemokinetic
      movement was fastest on airway epithelial surfaces covered with 1.5% mucus. In
      contrast, neutrophils exhibited little motility in any direction in thickened
      (6.5%) mucus. In in vivo models of airway mucus plugs, neutrophil migration was
      inhibited by thickened mucus (CF model) but not by normal concentrations of mucus
      ("normal" model). Paralleling the decreased neutrophil motility in thickened
      mucus, bacterial capture and killing capacity were decreased in CF-like thickened
      mucus. Similar results with each mucus concentration were obtained with mucus
      from CF cultures, indicating that inhibition of neutrophil functions was mucus
      concentration dependent not CF source dependent. We conclude that concentrated
      ("thick") mucus inhibits neutrophil migration and killing and is a key component
      in the failure of defense against chronic airways infection in CF.

PMID- 16002711
TI  - Critical role for the oligoadenylate synthetase/RNase L pathway in response to
      IFN-beta during acute ocular herpes simplex virus type 1 infection.
AB  - We previously demonstrated that IFN-beta transgene treatment protects mouse
      trigeminal ganglia (TG) cells from acute HSV-1 infection in vitro. However, IFN
      alpha6 transgene treatment does not provide protection against acute HSV-1
      infection in vitro, even though equivalent levels of IFN are expressed with both
      transgene treatments. In the present study we show that IFN-beta transgene
      treatment before acute ocular HSV-1 infection protects mice from HSV-1-mediated
      mortality, whereas IFN-alpha6 transgene treatment does not reduce mortality.
      Treatment with the IFN-beta and IFN-alpha6 transgenes was associated with
      increased expression of oligoadenylate synthetase (OAS)1a mRNA in the eye.
      However, protein kinase R mRNA was not up-regulated in the eye. In TG, only IFN
      beta transgene treatment reduced infectious virus levels. Furthermore, in the
      absence of a functional OAS pathway, corneal HSV-1 Ag expression was more
      widespread, and the ability of IFN-beta transgene treatment to reduce infectious
      HSV-1 in eyes and TG was lost. Along with selective up-regulation of OAS1a mRNA
      expression in TG from IFN-beta transgene-treated mice, we found increased levels
      of phospho-STAT1. Likewise, p38 MAPK phosphorylation was increased in TG from IFN
      beta transgene-treated mice, compared with both IFN-alpha6 and vector-treated
      mice. We also observed a time-dependent increase in JNK phosphorylation in TG
      from IFN-beta transgene-treated vs IFN-alpha6 and vector-treated mice. Our
      results demonstrate that IFN-beta is a potent antiviral cytokine that exerts
      protection against ocular HSV-1 infection via selective up-regulation of OAS1a
      mRNA in TG and by altering the phosphorylation of proteins in antiviral signaling
      cascades.

PMID- 16002712
TI  - Long-term control of Mycobacterium tuberculosis infection is mediated by dynamic
      immune responses.
AB  - The primary goal of this study was to determine how chronic exposure to Ag
      influences the functionality of Mycobacterium tuberculosis-specific T cell
      responses. The frequency of IFN-gamma-producing effector CD4(+) and CD8(+) T
      cells dynamically changed during persistent M. tuberculosis infection. CD8(+) T
      cells used differential effector functions during acute and chronic phases of the
      immune response, where CD8(+) T cells produced negligible amounts of IFN-gamma
      early in infection, but switched to cytokine production during the chronic stage
      of infection. Using limiting dilution analysis, CD8(+) T cells isolated during
      the initial phase of infection demonstrated lytic potential, but this waned in
      the chronic stage. The apparent loss of cytotoxic activity was not associated
      with the lack of perforin. Ag dose could potentially govern the functional
      program of CD8(+) T cells. Collectively, these results depict a host immune
      response mounted against M. tuberculosis of a significantly more dynamic nature
      than previously recognized.

PMID- 16002713
TI  - Lentivirus infection causes neuroinflammation and neuronal injury in dorsal root
      ganglia: pathogenic effects of STAT-1 and inducible nitric oxide synthase.
AB  - Distal sensory polyneuropathy (DSP) is currently the most common neurological
      complication of HIV infection in the developed world and is characterized by
      sensory neuronal injury accompanied by inflammation, which is clinically
      manifested as disabling pain and gait instability. We previously showed that
      feline immunodeficiency virus (FIV) infection of cats caused DSP together with
      immunosuppression in cats, similar to that observed in HIV-infected humans. In
      this study, we investigated the pathogenic mechanisms underlying the development
      of FIV-induced DSP using feline dorsal root ganglia (DRG) cultures, consisting of
      neurons, Schwann cells, and macrophages. FIV-infected cultures exhibited viral
      Ags (p24 and envelope) in macrophages accompanied by neuronal injury, indicated
      by neurite retraction, neuronal loss and decreased soma size, compared with mock
      infected (control) cultures. FIV infection up-regulated inducible NO synthase
      (iNOS), STAT-1, and TNF-alpha mRNA levels in DRG cultures. Increased STAT-1 and
      iNOS mRNA levels were also observed in DRGs from FIV-infected animals relative to
      mock-infected controls. Similarly, immunolabeling studies of DRGs from FIV
      infected animals showed that macrophages were the principal sources of STAT-1 and
      iNOS protein production. The iNOS inhibitor aminoguanidine reduced nitrotyrosine
      and protein carbonyl levels, together with preventing neuronal injury in FIV
      infected DRG cultures. The present studies indicate that FIV infection of DRGs
      directly contributes to axonal and neuronal injury through a mechanism involving
      macrophage immune activation, which is mediated by STAT-1 and iNOS activation.

PMID- 16002714
TI  - Developmentally regulated intestinal expression of IFN-gamma and its target genes
      and the age-specific response to enteric Salmonella infection.
AB  - Young infants are highly susceptible to systemic dissemination of enteric
      pathogens such as Salmonella typhimurium when compared with older individuals.
      The mechanisms underlying this differential susceptibility have not been defined
      clearly. To better understand this phenomenon, we examined the responses of adult
      mice and preweaned pups to oral infection by S. typhimurium. We found clear age
      specific differences, namely, an attenuated intestinal inflammatory response and
      a higher systemic bacterial burden in the pups compared with the adults. To
      elucidate the molecular basis for these differences, we obtained a microarray
      based profile of gene expression in the small intestines of uninfected adult and
      preweaned animals. The results indicated a striking age-dependent increase in the
      intestinal expression of a number of IFN-gamma-regulated genes involved in
      antimicrobial defense. This finding was confirmed by real-time quantitative PCR,
      which also demonstrated an age-dependent increase in intestinal expression of IFN
      gamma. The developmental up-regulation of the IFN-gamma-regulated genes was
      dependent on both IFN-gamma and a normal commensal microflora, as indicated by
      experiments in IFN-gamma-knockout mice and germfree mice, respectively. However,
      the increase in expression of IFN-gamma itself was independent of the commensal
      flora. The functional importance of IFN-gamma in the immunological maturation of
      the intestine was confirmed by the observation that the response of adult IFN
      gamma-knockout animals to S. typhimurium infection resembled that of the wild
      type pups. Our findings thus reveal a novel role for IFN-gamma in the
      developmental regulation of antimicrobial responses in the intestine.

PMID- 16002715
TI  - Invariant V alpha 14+ NKT cells participate in the early response to enteric
      Listeria monocytogenes infection.
AB  - Invariant Valpha14(+) NKT cells are a specialized CD1-reactive T cell subset
      implicated in innate and adaptive immunity. We assessed whether Valpha14(+) NKT
      cells participated in the immune response against enteric Listeria monocytogenes
      infection in vivo. Using CD1d tetramers loaded with the synthetic lipid alpha
      galactosylceramide (CD1d/alphaGC), we found that splenic and hepatic Valpha14(+)
      NKT cells in C57BL/6 mice were early producers of IFN-gamma (but not IL-4) after
      L. monocytogenes infection. Adoptive transfer of Valpha14(+) NKT cells derived
      from TCRalpha degrees Valpha14-Jalpha18 transgenic (TCRalpha degrees Valpha14Tg)
      mice into alymphoid Rag(null) gamma(c)(null) mice demonstrated that Valpha14(+)
      NKT cells were capable of providing early protection against enteric L.
      monocytogenes infection with systemic production of IFN-gamma and reduction of
      the bacterial burden in the liver and spleen. Rechallenge experiments
      demonstrated that previously immunized wild-type and Jalpha18null mice, but not
      TCRalpha(null) or TCRalpha(null) Valpha14Tg mice, were able to mount adaptive
      responses to L. monocytogenes. These data demonstrate that Valpha14(+) NKT cells
      are able to participate in the early response against enteric L. monocytogenes
      through amplification of IFN-gamma production, but are not essential for, nor
      capable of, mediating memory responses required to sterilize the host.

PMID- 16002716
TI  - Human rhinoviruses inhibit the accessory function of dendritic cells by inducing
      sialoadhesin and B7-H1 expression.
AB  - Dendritic cells (DC) are professional APCs with an unmatched ability to interact
      with and activate T cells. There is accumulating evidence that DC not only
      efficiently stimulate T cell activation but also regulate T cell responses.
      However, little is known about cell surface structures on DC involved in the
      regulation of T cell responses. We demonstrate that human rhinoviruses (HRV) can
      efficiently inhibit the accessory function of DC through induction of inhibitory
      cell surface receptors. We observed that treatment of DC with HRV14 (R-DC), a
      member of the major group HRV family, diminished their T cell stimulatory
      capacity and induced a promiscuous and deep anergic state in cocultured T cells
      despite high levels of MHC molecules as well as costimulatory molecules, e.g., B7
      1 (CD80) and B7-2 (CD86), and independent of inhibitory soluble factors such as
      IL-10. In contrast, expression of inhibitory B7-H1 molecules was up-regulated and
      R-DC de novo expressed sialoadhesin (Sn). Most importantly, blocking of B7-H1 and
      Sn on R-DC with specific mAbs against both receptors reverted the inhibitory
      phenotype. Thus, inhibitory signals delivered from R-DC to T cells via B7-H1 and
      Sn were critical for the induction of anergy. These observations suggest that an
      altered accessory molecule repertoire on DC upon interaction with HRV down
      modulates adaptive immune responses during the viral infection.

PMID- 16002717
TI  - Immunoproteasome-deficient mice mount largely normal CD8+ T cell responses to
      lymphocytic choriomeningitis virus infection and DNA vaccination.
AB  - During viral infection, constitutive proteasomes are largely replaced by
      immunoproteasomes, which display distinct cleavage specificities, resulting in
      different populations of potential CD8(+) T cell epitope peptides.
      Immunoproteasomes are believed to be important for the generation of many viral
      CD8(+) T cell epitopes and have been implicated in shaping the immunodominance
      hierarchies of CD8(+) T cell responses to influenza virus infection. However, it
      remains unclear whether these conclusions are generally applicable. In this study
      we investigated the CD8(+) T cell responses to lymphocytic choriomeningitis virus
      infection and DNA immunization in wild-type mice and in mice lacking the
      immunoproteasome subunits LMP2 or LMP7. Although the total number of virus
      specific cells was lower in LMP2 knockout mice, consistent with their having
      lower numbers of naive cells before infection, the kinetics of virus clearance
      were similar in all three mouse strains, and LMP-deficient mice mounted strong
      primary and secondary lymphocytic choriomeningitis virus-specific CD8(+) T cell
      responses. Furthermore, the immunodominance hierarchy of the four investigated
      epitopes (nuclear protein 396 (NP(396)) > gp33 > gp276 > NP(205)) was well
      maintained. We observed a slight reduction in the NP(205)-specific response in
      LMP2-deficient mice, but this had no demonstrable biological consequence. DNA
      vaccination of LMP2- and LMP7-deficient mice induced CD8(+) T cell responses that
      were slightly lower than, although not significantly different from, those
      induced in wild-type mice. Taken together, our results challenge the notion that
      immunoproteasomes are generally needed for effective antiviral CD8(+) T cell
      responses and for the shaping of immunodominance hierarchies. We conclude that
      the immunoproteasome may affect T cell responses to only a limited number of
      viral epitopes, and we propose that its main biological function may lie
      elsewhere.

PMID- 16002718
TI  - 18 Beta-glycyrrhetinic acid triggers curative Th1 response and nitric oxide up
      regulation in experimental visceral leishmaniasis associated with the activation
      of NF-kappa B.
AB  - The efficacy of 18beta-glycyrrhetinic acid (GRA), a pentacyclic triterpene
      belonging to the beta-amyrin series of plant origin, was evaluated in
      experimental visceral leishmaniasis. GRA is reported to have antitumor and
      immunoregulatory activities, which may be attributable in part to the induction
      of NO. Indeed, an 11-fold increase in NO production was observed with 20 microM
      GRA in mouse peritoneal macrophages infected with Leishmania donovani
      promastigotes. In addition to having appreciable inhibitory effects on amastigote
      multiplication within macrophages (IC(50), 4.6 microg/ml), complete elimination
      of liver and spleen parasite burden was achieved by GRA at a dose of 50
      mg/kg/day, given three times, 5 days apart, in a 45-day mouse model of visceral
      leishmaniasis. GRA treatment resulted in reduced levels of IL-10 and IL-4, but
      increased levels of IL-12, IFN-gamma, TNF-alpha, and inducible NO synthase,
      reflecting a switch of CD4(+) differentiation from Th2 to Th1. This treatment is
      likely to activate immunity, thereby imparting resistance to reinfection. GRA
      induced NF-kappaB migration into the nucleus of parasite-infected cells and
      caused a diminishing presence of IkappaB in the cytoplasm. The lower level of
      cytoplasmic IkappaBalpha in GRA-treated cells resulted from increased
      phosphorylation of IkappaBalpha and higher activity of IkappaB kinase (IKK).
      Additional experiments demonstrated that GRA does not directly affect IKK
      activity. These results suggest that GRA exerts its effects at some level
      upstream of IKK in the signaling pathway and induces the production of
      proinflammatory mediators through a mechanism that, at least in part, involves
      induction of NF-kappaB activation.

PMID- 16002719
TI  - Diminished expression and function of TLR in lymphatic filariasis: a novel
      mechanism of immune dysregulation.
AB  - Lymphatic filariasis is a disease characterized by immune dysregulation involving
      APC and T cell populations. To assess the contribution of TLR in mediating this
      dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B
      cells and monocytes of filaria-infected and uninfected individuals. Baseline
      expression of TLR was significantly lower in B cells but not in monocytes of the
      filaria-infected group compared with the uninfected group. Upon stimulation with
      filarial Ag, a diminished up-regulation of TLR was observed in both B cells and
      monocytes of infected individuals. Finally, stimulation of B cells and monocytes
      with TLR ligands resulted in decreased B cell and monocyte activation/cytokine
      production, indicating a state of immune tolerance. This dysregulation is
      associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The
      diminished expression and function of TLR is thus a likely consequence of chronic
      Ag stimulation and could serve as a novel mechanism underlying the dysfunctional
      immune response in filariasis.

PMID- 16002720
TI  - Priming effect of lipopolysaccharide on acetyl-coenzyme A:lyso-platelet
      activating factor acetyltransferase is MyD88 and TRIF independent.
AB  - LPS has a priming effect on various stimuli. For instance, LPS priming enhances
      the production of platelet-activating factor (PAF), a proinflammatory lipid
      mediator that is induced by PAF itself. Among various enzymes responsible for PAF
      biosynthesis, acetyl-coenzyme A:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine
      acetyltransferase is one of the enzymes activated by PAF receptor stimulation. In
      this study we investigated the priming effect of LPS on the acetyltransferase
      activation by PAF in TLR4-knockout (KO) mice, MyD88-KO mice, and Toll/IL-1R
      domain-containing adaptor inducing IFN-beta (TRIF)-KO mice. This enzyme was
      biphasically activated by LPS. Although the first peak occurred within 30 min in
      wild-type (WT), but not TLR4-KO or MyD88-KO, macrophages, the second phase
      reached a maximum within hours in WT, MyD88-KO, and TRIF-KO, but not in TLR4-KO,
      macrophages. Only in the second phase was the increase in acetyltransferase
      activity upon PAF receptor activation remarkably enhanced in WT, MyD88-KO, and
      TRIF-KO cells, but not in TLR4-KO cells. These data demonstrated that LPS exerted
      a priming effect on PAF receptor-mediated acetyltransferase activation through
      the TLR4-dependent, but MyD88- and TRIF-independent, pathway.

PMID- 16002721
TI  - Induction of humoral and CD8+ T cell responses are required for protection
      against lethal Ebola virus infection.
AB  - Ebola virus (EBOV)-like particles (eVLP), composed of the EBOV glycoprotein and
      matrix viral protein (VP)40 with a lipid membrane, are a highly efficacious
      method of immunization against EBOV infection. The exact requirements for
      immunity against EBOV infection are poorly defined at this time. The goal of this
      work was to determine the requirements for EBOV immunity following eVLP
      vaccination. Vaccination of BALB/c or C57BL/6 mice with eVLPs in conjunction with
      QS-21 adjuvant resulted in mixed IgG subclass responses, a Th1-like memory
      cytokine response, and protection from lethal EBOV challenge. Further, this
      vaccination schedule led to the generation of both CD4(+) and CD8(+) IFN-gamma(+)
      T cells recognizing specific peptides within glycoprotein and VP40. The transfer
      of both serum and splenocytes, but not serum or splenocytes alone, from eVLP
      vaccinated mice conferred protection against lethal EBOV infection in these
      studies. B cells were required for eVLP-mediated immunity to EBOV because B cell
      deficient mice vaccinated with eVLPs were not protected from lethal EBOV
      challenge. We also found that CD8(+), but not CD4(+), T cells are absolutely
      required for eVLP-mediated protection against EBOV infection. Further, eVLP
      induced protective mechanisms were perforin-independent, but IFN-gamma-dependent.
      Taken together, both EBOV-specific humoral and cytotoxic CD8(+) T cell responses
      are critical to mediate protection against filoviruses following eVLP
      vaccination.

PMID- 16002722
TI  - An intact phosphocholine binding site is necessary for transgenic rabbit C
      reactive protein to protect mice against challenge with platelet-activating
      factor.
AB  - C-reactive protein (CRP), an acute phase protein in humans and rabbits, is part
      of the innate immune system. The role of CRP in host defense has been thought to
      be largely due to its ability to bind phosphocholine, activate complement, and
      interact with IgGRs (FcgammaRs). We have shown previously that transgenic rabbit
      CRP (rbCRP) protects mice from lethal challenges with platelet-activating factor
      (PAF). To investigate the mechanism of this protection, we created additional
      lines of transgenic mice that express either wild-type rbCRP, a variant of rbCRP
      with altered complement activation activity (Y175A), or a variant of rbCRP unable
      to bind phosphocholine (F66Y/E81K). In the current study, these lines were
      challenged with a single injection of PAF and their survival monitored. Mice
      expressing wild-type and Y175A rbCRP were protected against challenge by PAF
      whereas mice expressing F66Y/E81K rbCRP were not. Treatment with cobra venom
      factor did not affect survival, confirming the results with the Y175A rbCRP
      variant and indicating that complement activation was not required to mediate
      protection. Both wild-type rbCRP and Y175A rbCRP were capable of binding PAF in
      vitro whereas F66Y/E81K rbCRP was not. Although other interpretations are
      possible, our results suggest that the protective effect of rbCRP against PAF is
      due to sequestration of PAF.

PMID- 16002723
TI  - Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and
      JNK.
AB  - Tumor-associated macrophages may influence tumor progression, angiogenesis and
      invasion. To investigate mechanisms by which macrophages interact with tumor
      cells, we developed an in vitro coculture model. Previously we reported that
      coculture enhanced invasiveness of the tumor cells in a TNF-alpha- and matrix
      metalloprotease-dependent manner. In this report, we studied intracellular
      signaling pathways and induction of inflammatory genes in malignant cells under
      the influence of macrophage coculture. We report that coculture of macrophages
      with ovarian or breast cancer cell lines led to TNF-alpha-dependent activation of
      JNK and NF-kappaB pathways in tumor cells, but not in benign immortalized
      epithelial cells. Tumor cells with increased JNK and NF-kappaB activity exhibited
      enhanced invasiveness. Inhibition of the NF-kappaB pathway by TNF-alpha
      neutralizing Abs, an NF-kappaB inhibitor, RNAi to RelA, or overexpression of
      IkappaB inhibited tumor cell invasiveness. Blockade of JNK also significantly
      reduced invasiveness, but blockade of p38 MAPK or p42 MAPK had no effect.
      Cocultured tumor cells were screened for the expression of 22 genes associated
      with inflammation and invasion that also contained an AP-1 and NF-kappaB binding
      site. EMMPRIN and MIF were up-regulated in cocultured tumor cells in a JNK- and
      NF-kappaB-dependent manner. Knocking down either MIF or EMMPRIN by RNAi in the
      tumor cells significantly reduced tumor cell invasiveness and matrix
      metalloprotease activity in the coculture supernatant. We conclude that TNF
      alpha, via NF-kappaB, and JNK induces MIF and EMMPRIN in macrophage to tumor cell
      cocultures and this leads to increased invasive capacity of the tumor cells.

PMID- 16002724
TI  - Alterations in nitric oxide and cytokine production with airway inflammation in
      the absence of IL-10.
AB  - IL-10 is an anti-inflammatory cytokine that suppresses NO synthase (NOS) and
      production of NO; its lack may promote NO production and alterations in cytokines
      modulated by NO with allergic airway inflammation (AI), such as IL-18 and IL-4.
      Therefore, we induced AI in IL-10 knockout ((-/-)) and IL-10-sufficient C57BL/6
      (C57) mice with inhaled OVA and measured airway NO production, as exhaled NO
      (E(NO)) and bronchoalveolar lavage fluid nitrite levels. E(NO) and nitrite levels
      were elevated significantly in naive IL-10(-/-) mice as compared with C57 mice.
      With AI, E(NO) and nitrite levels increased in C57 mice and decreased in IL-10(-/
      ) mice. IL-18 production fell with both AI and addition of S-nitroso-N-acetyl-d,l
      penicillamine (a NO donor) but was not significantly increased by chemical NOS
      inhibition by l-N(5)-(1-iminoethyl)-ornithine. IL-4 AI was increased
      significantly (up to 10-fold greater) in the absence of IL-10 but was reduced
      significantly with chemical inhibition of NOS. Airway responsiveness was lower in
      IL-10(-/-) mice and was associated with alteration in production of NO and IL-4.
      Thus, IL-4 production was increased, and likely decreased NO production, in a way
      not predicted by the absence of IL-10. Inhibition of IL-4 production, with
      inhibition of NOS in the absence of IL-10, demonstrated the importance of a NO
      and IL-4 feedback mechanism regulating this interaction.

PMID- 16002725
TI  - Influence of beta 1 integrin intracytoplasmic domains in the regulation of VLA-4
      mediated adhesion of human T cells to VCAM-1 under flow conditions.
AB  - The VLA-4 integrin supports static cell-cell, cell-matrix adhesion, and dynamic
      interactions with VCAM-1. Although functions for well-conserved beta(1) integrin
      cytoplasmic domains in regulating static cell adhesion has been established, the
      molecular basis for beta(1) integrin-dependent arrest on VCAM-1 under flow
      conditions remains poorly understood. We have transfected the beta(1) integrin
      deficient A1 Jurkat T cell line with beta(1) cDNA constructs with deletions of
      the NPXY motifs and specific mutations of tyrosine residues. Deletion of either
      NPXY motif impaired static adhesion induced by CD2 or CD47 triggering or direct
      beta(1) integrin stimulation. In contrast, PMA-induced adhesion to VCAM-1 was
      unaffected by deletion of the NPIY motif and only slightly impaired by deletion
      of NPKY. Moreover, deletion of the NPIY motif resulted in enhanced rolling and
      reduced arrest on VCAM-1 under shear flow conditions. In contrast, deletion of
      the NPKY motif did not alter arrest under flow. Although tyrosine to
      phenylalanine substitutions within two NPXY motifs did not alter static adhesion
      to VCAM-1, these mutations enhanced arrest on VCAM-1 under flow conditions.
      Furthermore, although deletion of the C'-terminal 5 AA of the beta(1) cytoplasmic
      domain dramatically impaired activation-dependent static adhesion, it did not
      impair arrest on VCAM-1 under flow conditions. Thus, our results demonstrate
      distinct structural requirements for VLA-4 function under static and shear flow
      conditions. This may be relevant for VLA-4 activity regulation in different
      anatomic compartments, such as when circulating cells arrest on inflamed
      endothelium under shear flow and when resident cells in bone marrow interact with
      VCAM-1- positive stromal cells.

PMID- 16002726
TI  - Anti-vascular endothelial growth factor gene therapy attenuates lung injury and
      fibrosis in mice.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenesis factor with
      proinflammatory roles. Flt-1 is one of the specific receptors for VEGF, and
      soluble flt-1 (sflt-1) binds to VEGF and competitively inhibits it from binding
      to the receptors. We examined the role of VEGF in the pathophysiology of
      bleomycin-induced pneumopathy in mice, using a new therapeutic strategy that
      comprises transfection of the sflt-1 gene into skeletal muscles as a biofactory
      for anti-VEGF therapy. The serum levels of sflt-1 were significantly increased at
      3-14 days after the gene transfer. Transfection of the sflt-1 gene at 3 days
      before or 7 days after the intratracheal instillation of bleomycin decreased the
      number of inflammatory cells, the protein concentration in the bronchoalveolar
      lavage fluid and with von Willebrand factor expression at 14 days. Transfection
      of the sflt-1 gene also attenuated pulmonary fibrosis and apoptosis at 14 days.
      Since the inflammatory cell infiltration begins at 3 days and is followed by
      interstitial fibrosis, it is likely that VEGF has important roles as a
      proinflammatory, a permeability-inducing, and an angiogenesis factor not only in
      the early inflammatory phase but also in the late fibrotic phase. Furthermore,
      this method may be beneficial for treating lung injury and fibrosis from the
      viewpoint of clinical application, since it does not require the use of a viral
      vector or neutralizing Ab.

PMID- 16002727
TI  - Elimination of senescent neutrophils by TNF-related apoptosis-inducing
      [corrected] ligand.
AB  - Neutrophils are phagocytic effectors which are produced in the bone marrow and
      released into the circulation. Thereafter, they are either recruited to sites of
      inflammation or rapidly become senescent, return to the bone marrow, and undergo
      apoptosis. Stromal cell-derived factor 1 (SDF-1) coordinates the return of
      senescent neutrophils to the bone marrow by interacting with CXCR4 that is
      preferentially expressed on senescent neutrophils. We demonstrate that CXCR4
      ligation by SDF-1 or other CXCR4 agonists significantly increases the expression
      of both TNF-related apoptosis-inducing [corrected] ligand (TRAIL) and of the
      death-inducing TRAIL receptors on neutrophils, which confers an acquired
      sensitivity to TRAIL-mediated death and results in TRAIL-dependent apoptosis. In
      vivo administration of TRAIL antagonists results in neutrophilic accumulation
      within the bone marrow and a reduction in neutrophil apoptosis; conversely
      recombinant TRAIL administration reduced neutrophil number within bone marrow.
      Thus, SDF-1 ligation of CXCR4 causes the parallel processes of chemotaxis and
      enhanced TRAIL and TRAIL death receptor expression, resulting in apoptosis of
      senescent neutrophils upon their return to the bone marrow.

PMID- 16002728
TI  - CD93 is rapidly shed from the surface of human myeloid cells and the soluble form
      is detected in human plasma.
AB  - CD93 is a highly glycosylated transmembrane protein expressed on monocytes,
      neutrophils, endothelial cells, and stem cells. Antibodies directed at CD93
      modulate phagocytosis, and CD93-deficient mice are defective in the clearance of
      apoptotic cells from the inflamed peritoneum. In this study we observe that CD93,
      expressed on human monocytes and neutrophils, is susceptible to phorbol
      dibutyrate-induced protein ectodomain shedding in a time- and dose-dependent
      manner. The soluble fragment found in culture supernatant retains the N-terminal
      carbohydrate recognition domain and the epidermal growth factor repeats after
      ectodomain cleavage. Importantly, a soluble form of the CD93 ectodomain was
      detected in human plasma, demonstrating that shedding is a physiologically
      relevant process. Inhibition of metalloproteinases with 1,10-phenanthroline
      inhibited shedding, but shedding was independent of TNF-alpha-converting enzyme
      (a disintegrin and metalloproteinase 17). Phorbol dibutyrate-induced CD93
      shedding on monocytes was accompanied by decreased surface expression, whereas
      neutrophils displayed an increase in surface expression, suggesting that CD93
      shed from the neutrophil surface was rapidly replaced by CD93 from intracellular
      stores. Cross-linking CD93 on human monocytes with immobilized anti-CD93 mAbs
      triggered shedding, as demonstrated by a decrease in cell-associated, full-length
      CD93 concomitant with an increase in CD93 intracellular domain-containing
      cleavage products. In addition, the inflammatory mediators, TNF-alpha and LPS,
      stimulated ectodomain cleavage of CD93 from monocytes. These data demonstrate
      that CD93 is susceptible to ectodomain shedding, identify multiple stimuli that
      trigger shedding, and identify both a soluble form of CD93 in human plasma and
      intracellular domain containing cleavage products within cells that may
      contribute to the physiologic role of CD93.

PMID- 16002729
TI  - Mechanisms underlying resistance of pancreatic islets from ALR/Lt mice to
      cytokine-induced destruction.
AB  - Nuclear and mitochondrial genomes combine in ALR/Lt mice to produce systemically
      elevated defenses against free radical damage, rendering these mice resistant to
      immune-mediated pancreatic islet destruction. We analyzed the mechanism whereby
      isolated islets from ALR mice resisted proinflammatory stress mediated by
      combined cytokines (IL-1beta, TNF-alpha, and IFN-gamma) in vitro. Such damage
      entails both superoxide and NO radical generation, as well as peroxynitrite,
      resulting from their combination. In contrast to islets from other mouse strains,
      ALR islets expressed constitutively higher glutathione reductase, glutathione
      peroxidase, and higher ratios of reduced to oxidized glutathione. Following
      incubation with combined cytokines, islets from control strains produced
      significantly higher levels of hydrogen peroxide and NO than islets from ALR
      mice. Nitrotyrosine was generated in NOD and C3H/HeJ islets but not by ALR
      islets. Western blot analysis showed that combined cytokines up-regulated the NF
      kappaB inducible NO synthase in NOD-Rag and C3H/HeJ islets but not in ALR islets.
      This inability of cytokine-treated ALR islets to up-regulate inducible NO
      synthase and produce NO correlated both with reduced kinetics of IkappaB
      degradation and with markedly suppressed NF-kappaB p65 nuclear translocation.
      Hence, ALR/Lt islets resist cytokine-induced diabetogenic stress through enhanced
      dissipation and/or suppressed formation of reactive oxygen and nitrogen species,
      impaired IkappaB degradation, and blunted NF-kappaB activation. Nitrotyrosylation
      of beta cell proteins may generate neoantigens; therefore, resistance of ALR
      islets to nitrotyrosine formation may, in part, explain why ALR mice are
      resistant to type 1 diabetes when reconstituted with a NOD immune system.

PMID- 16002730
TI  - A non-glycosaminoglycan-binding variant of CC chemokine ligand 7 (monocyte
      chemoattractant protein-3) antagonizes chemokine-mediated inflammation.
AB  - A non-glycosaminoglycan (GAG)-binding variant of the pleiotropic chemokine CCL7
      was generated by mutating to alanine the basic (B) amino acids within an
      identified (44)BXBXXB(49) GAG-binding motif. Unlike wild-type (wt) CCL7, the
      mutant sequence had no affinity for heparin. However, the mutant retained a
      normal affinity for CCR1, CCR2b, and CCR3, and produced a normal calcium flux in
      mononuclear leukocytes. Both the wt and mutant proteins elicited an equal
      leukocyte chemotactic response within a solute diffusion gradient but, unlike the
      wt protein, the mutant failed to stimulate cell migration across a model
      endothelium. The number of leukocytes recruited to murine air pouches by the
      mutant sequence was lower than that recruited by wt CCL7. Furthermore, the
      presence of a mixture of a mutant and wt CCL7 within the air pouch elicited no
      significant cell accumulation. Cell recruitment also failed using a receptor
      sharing mixture of mutant CCL7 and wt CCL5 or a nonreceptor sharing mixture of
      mutant CCL7 and wt CXCL12. The potential of the mutant sequence to modulate
      inflammation was confirmed by demonstration of its ability to inhibit the
      chemotactic response generated in vitro by synovial fluid from patients with
      active rheumatoid arthritis. A further series of experiments suggested that the
      non-GAG-binding mutant protein could potentially induce receptor desensitization
      before, and at a site remote from, any physiological recognition of GAG-bound
      chemokines. These data demonstrate that GAG binding is required for chemokine
      driven inflammation in vivo and also suggest that a non-GAG-binding chemokine
      receptor agonist can inhibit the normal vectorial leukocyte migration mediated by
      chemokines.

PMID- 16002731
TI  - P-selectin glycoprotein ligand 1 is not required for the development of
      experimental autoimmune encephalomyelitis in SJL and C57BL/6 mice.
AB  - In multiple sclerosis and in its animal model experimental autoimmune
      encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood
      brain barrier and gain access to the CNS. The involvement of P-selectin
      glycoprotein ligand 1 (PSGL-1) and of its major endothelial ligand P-selectin in
      this process have been controversial. In this study we demonstrate that although
      encephalitogenic T cells express functional PSGL-1, which can bind to soluble and
      immobilize P-selectin if presented in high concentrations, PSGL-1 is not involved
      T cell interaction with P-selectin expressing brain endothelial cells in vitro.
      Furthermore, neither anti-PSGL-1 Abs nor the lack of PSGL-1 in PSGL-1-deficient
      mice inhibits the recruitment of inflammatory cells across the blood-brain
      barrier or the development of clinical EAE. Taken together, our findings
      demonstrate that PSGL-1 is not required for the pathogenesis of EAE.

PMID- 16002732
TI  - Mucosal B cell deficiency in IgA-/- mice abrogates the development of allergic
      lung inflammation.
AB  - We have investigated the consequence of lack of IgA on host immunity using a
      murine model of allergic lung inflammation. Mice with a targeted disruption of
      the alpha-switch region and 5' H chain gene (IgA(-/-) mice), which lack total
      IgA, developed significantly reduced pulmonary inflammation with fewer
      inflammatory cells in lung tissue and bronchoalveolar lavage fluids, as well as
      reduced levels of total and IgG1 OVA-specific Abs and decreased IL-4 and IL-5 in
      bronchoalveolar lavage fluids compared with IgA(+/+) controls, following allergen
      sensitization and challenge. This defect was attributable to fewer B cells in the
      lungs of IgA(-/-) mice. Polymeric IgR-deficient (pIgR(-/-)) mice, which lack the
      receptor that transports polymeric IgA across the mucosal epithelium where it is
      cleaved to form secretory IgA, were used to assess the contribution of secretory
      IgA vs total IgA in the induction of allergic lung inflammation. pIgR(-/-) and
      pIgR(+/+) mice had comparable levels of inflammation, demonstrating that IgA
      bound to secretory component is not necessary for the development of allergic
      lung inflammation, although this does not necessarily rule out a role for
      transudated IgA in lung secretions because of "mucosal leakiness" in these mice.
      The results indicate that Ag-specific B cells are required at mucosal surfaces
      for induction of inflammation and likely function as major APCs in the lung for
      soluble protein Ags.

PMID- 16002733
TI  - Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium
      binding proteins, can induce Th cell type 1-mediated autoreactivity.
AB  - Skin inflammation in atopic dermatitis starts with Th2 and IgE-mediated responses
      against exogenous allergens and, for unknown reasons, resembles features of a Th1
      driven reaction in the chronic stages. We report the characterization of a human
      protein, Hom s 4, recognized by IgE autoantibodies from atopic dermatitis
      patients. The complete Hom s 4 cDNA codes for a 54-kDa basic protein containing
      two typical calcium-binding domains separated by an unusually long alpha-helical
      domain. Therefore, Hom s 4 and homologous proteins found by sequence comparison
      in mice, fruit flies, and nematodes constitute a novel subfamily of calcium
      binding proteins. Using Hom s 4-specific Abs, it is demonstrated that the protein
      is strongly expressed within epidermal keratinocytes and dermal endothelial
      cells. Purified Hom s 4 showed IgE cross-reactivity with exogenous calcium
      binding allergens from plants and fish but, in contrast to the exogenous
      allergens, induced only weak histamine release from patient basophils. However,
      the analysis of Hom s 4-specific cytokine and humoral immune responses indicated
      that Hom s 4 strongly induces Th1 responses which are accompanied by the release
      of IFN-gamma, a cytokine implicated in epithelial cell damage. Hom s 4-induced
      IFN-gamma production was found in normal individuals, in patients with chronic
      inflammatory skin diseases and in Th2-prone atopic persons, suggesting that Hom s
      4 represents a protein with an intrinsic property to induce Th1-mediated
      autoreactivity. It may thus contribute to chronic skin inflammation in atopic as
      well as in nonatopic persons.

PMID- 16002734
TI  - Contribution of the lymphotoxin beta receptor to liver regeneration.
AB  - The liver has an enormous capacity to regenerate in response to insults, but the
      cellular events and molecules involved in liver regeneration are not well
      defined. In this study, we report that ligands expressed on the surface of
      lymphocytes have a substantial effect on liver homeostasis. We demonstrate that a
      T cell-restricted ligand, homologous to lymphotoxin, exhibits inducible
      expression, competes with herpesvirus glycoprotein D for herpesvirus entry
      mediator on T cells (LIGHT), signaling through the lymphotoxin receptor (LTbetaR)
      expressed on mature hepatocytes induces massive hepatomegaly. Using genetic
      targeting and a receptor fusion protein, we further show that mice deficient in
      LTbetaR signaling have a severe defect in their ability to survive partial
      hepatectomy with marked liver damage and failure to initiate DNA synthesis after
      partial hepatectomy. We further show that mice deficient in a LTbetaR ligand,
      LTalpha, also show decreased ability to survive partial hepatectomy with similar
      levels of liver damage and decreased DNA synthesis. Therefore, our study has
      revealed an unexpected role of lymphocyte-restricted ligands and defined a new
      pathway in supporting liver regeneration.

PMID- 16002735
TI  - Targeting positive regulatory domain I-binding factor 1 and X box-binding protein
      1 transcription factors by multiple myeloma-reactive CTL.
AB  - Growing evidence indicates that multiple myeloma (MM) and other malignancies are
      susceptible to CTL-based immune interventions. We studied whether transcription
      factors inherently involved in the terminal differentiation of mature B
      lymphocytes into malignant and nonmalignant plasma cells provide MM-associated
      CTL epitopes. HLA-A*0201 (A2.1) transgenic mice were used to identify A2.1
      presented peptide Ag derived from the plasma cell-associated transcriptional
      regulators, positive regulatory domain I-binding factor 1 (PRDI-BF1) and X box
      binding protein 1 (XBP-1). A2.1-restricted CTL specific for PRDI-BF1 and XBP-1
      epitopes efficiently killed a variety of MM targets. PRDI-BF1- and XBP-1-reactive
      CTL were able to recognize primary MM cells from A2.1(+) patients. Consistent
      with the expression pattern of both transcription factors beyond malignant and
      nonmalignant plasma cells, PRDI-BF1- and XBP-1-specific CTL activity was not
      entirely limited to MM targets, but was also associated with lysis of certain
      other malignancies and, in defined instances, with low-to-intermediate level
      recognition of a few types of normal cells. Our results also indicate that the
      A2.1-restricted, PRDI-BF1- and XBP-1-specific human CD8(+) T cell repertoire is
      affected by partial self tolerance and may thus require the transfer of high
      affinity TCR to break tolerance. We conclude that transcription factors governing
      terminal cellular differentiation may provide MM- and tumor-associated CTL
      epitopes.

PMID- 16002737
TI  - Host-residual invariant NK T cells attenuate graft-versus-host immunity.
AB  - Invariant NK T (iNKT) cells have an invariant TCR-alpha chain and are activated
      in a CD1d-restricted manner. They are thought to regulate immune responses and
      play important roles in autoimmunity, allergy, infection, and tumor immunity.
      They also appear to influence immunity after hemopoietic stem cell
      transplantation. In this study, we examined the role of iNKT cells in graft-vs
      host disease (GVHD) and graft rejection in a mouse model of MHC-mismatched bone
      marrow transplantation, using materials including alpha-galactosylceramide, NKT
      cells expanded in vitro, and Jalpha18 knockout mice that lack iNKT cells. We
      found that host-residual iNKT cells constitute effector cells which play a
      crucial role in reducing the severity of GVHD, and that this reduction is
      associated with a delayed increase in serum Th2 cytokine levels. Interestingly,
      we also found that host-residual iNKT cause a delay in engraftment and, under
      certain conditions, graft rejection. These results indicate that host-residual
      iNKT cells attenuate graft-vs-host immunity rather than host-vs-graft immunity.

PMID- 16002736
TI  - IL-1 beta induces IL-6 expression in human orbital fibroblasts: identification of
      an anatomic-site specific phenotypic attribute relevant to thyroid-associated
      ophthalmopathy.
AB  - Human orbital fibroblasts exhibit a unique inflammatory phenotype. In the present
      study, we report that these fibroblasts, when treated with IL-1beta, express high
      levels of IL-6, a cytokine involved in B cell activation and the regulation of
      adipocyte metabolism. The magnitude of this induction is considerably greater
      than that in dermal fibroblasts and involves up-regulation of IL-6 mRNA levels.
      IL-1beta activates both p38 and ERK 1/2 components of the MAPK pathways.
      Disrupting these could attenuate the IL-6 induction. The up-regulation involves
      enhanced IL-6 gene promoter activity and retardation of IL-6 mRNA decay by IL
      1beta. Dexamethasone completely blocked the effect of IL-1beta on IL-6
      expression. Orbital fibroblasts also express higher levels of IL-6R than do skin
      derived cells. When treated with rIL-6 (10 ng/ml), STAT3 is transiently
      phosphorylated. Thus, the exaggerated capacity of orbital fibroblasts to express
      high levels of both IL-6 and its receptor in an anatomic site-selective manner
      could represent an important basis for immune responses localized to the orbit in
      Graves' disease.

PMID- 16002738
TI  - Genotype-proteotype linkage in the Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is a platelet/immunodeficiency disease arising
      from mutations of WAS protein (WASP), a hemopoietic cytoskeletal protein.
      Clinical symptoms vary widely from mild (X-linked thrombocytopenia) to life
      threatening. In this study, we examined the molecular effects of individual
      mutations by quantifying WASP in peripheral lymphocytes of 44 patients and
      identifying the molecular variant (collectively called proteotype). Nonpredicted
      proteotypes were found for 14 genotypes. These include WASP-negative lymphocytes
      found for five missense genotypes and WASP-positive lymphocytes for two nonsense,
      five frameshift, and two splice site genotypes. Missense mutations in the
      Ena/VASP homology 1 (EVH1) domain lead to decreased/absent WASP but normal mRNA
      levels, indicating that proteolysis causes the protein deficit. Because several
      of the EVH1 missense mutations alter WIP binding sites, the findings suggest that
      abrogation of WIP binding induces proteolysis. Whereas platelets of most patients
      were previously shown to lack WASP, WASP-positive platelets were found for two
      atypical patients, both of whom have mutations outside the EVH1 domain. WASP
      variants with alternative splicing and intact C-terminal domains were
      characterized for eight nonsense and frameshift genotypes. One of these, a
      nonsense genotype in a mild patient, supports expression of WASP lacking half of
      the proline-rich region. With one notable exception, genotype and proteotype were
      linked, indicating that a genotype-proteotype registry could be assembled to aid
      in predicting disease course and planning therapy for newly diagnosed infants.
      Knowledge of the molecular effect of mutations would aid also in identifying
      disease-modifying genes.

PMID- 16002739
TI  - Genetic dissection of systemic lupus erythematosus pathogenesis: partial
      functional complementation between Sle1 and Sle3/5 demonstrates requirement for
      intracellular coexpression for full phenotypic expression of lupus.
AB  - Sle1 on chromosome 1 and Sle3/5 on chromosome 7 are two of the most critical
      lupus susceptibility loci of the New Zealand Black/White-derived NZM2410 mouse
      strain. In contrast to C57BL/6 mice congenic for either Sle1 (B6.Sle1) or Sle3/5
      (B6.Sle3/5), strains that express only a modest lupus-related phenotype, the
      bicongenic B6.Sle1.Sle3/5 strain has a robust phenotype, suggesting a critical
      role for epistatic interactions in lupus pathogenesis. Mixed chimera experiments
      indicated that the two loci are functionally expressed by different cell
      populations and predicted that phenotypic expression of the phenotypic features
      of the B6.Sle1.Sle3/5 strain could be fully reproduced with a combination of
      B6.Sle1 and B6.Sle3/5 bone marrow. Contrary to our expectations, there was only a
      partial functional complementation in these mixed chimeras. Spleen enlargement,
      CD4:CD8 ratio elevation, and epitope spreading of autoantibodies were fully
      developed in B6+B6.Sle1.Sle3/5 but not in B6.Sle1+B6.Sle3/5 mixed chimeras. This
      study is the first to present evidence that the pathways mediated by two critical
      lupus susceptibility loci derived from the New Zealand White strain must be
      integrated intracellularly for epistatic interactions to occur. Our mixed chimera
      approach continues to provide novel insights into the functional genetic pathways
      underlying this important murine model of systemic autoimmunity.

PMID- 16002740
TI  - Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of
      the naturally occurring LPLS447X beneficial mutation.
AB  - The naturally occurring human lipoprotein lipase S447X variant (LPLS447X)
      exemplifies a gain-of function mutation with significant benefits including
      decreased plasma triglycerides (TG), increased high-density lipoprotein (HDL)
      cholesterol, and reduced risk of coronary artery disease. The S447X variant may
      be associated with higher LPL catalytic activity; however, in vitro data
      supporting this hypothesis are contradictory. We wanted to investigate the in
      vivo mechanism by which the LPLS447X variant improves the lipid profile of S447X
      carriers. We conducted a functional assessment of human LPLS447X compared with
      LPLWT in mice. LPL variants were compared in the absence of endogenous mouse LPL
      in newborn LPL(-/-) mice by adenoviral-mediated gene transfer. LPL(-/-) mice
      normally exhibit severe hypertriglyceridemia and die within 48 hours of birth.
      LPLWT gene transfer prolonged the survival of mice up to 21 days. In contrast,
      LPLS447X completely rescued 95% of the mice to adulthood and increased LPL
      catalytic activity in postheparin plasma 2.1-fold compared with LPLWT at day 3
      (P=0.003). LPLS447X also reduced plasma TG 99% from baseline (P<0.001), 2-fold
      more than LPLWT, (P<0.01) and increased plasma HDL cholesterol 2.9-fold higher
      than LPLWT (P<0.01). These data provide in vivo evidence that the increased
      catalytic activity of LPLS447X improves plasma TG clearance and increases the HDL
      cholesterol pool compared with LPLWT.

PMID- 16002741
TI  - Rho-kinase is an important therapeutic target in cardiovascular medicine.
AB  - Rho-kinase has been identified as one of the effectors of the small GTP-binding
      protein Rho. Accumulating evidence has demonstrated that Rho/Rho-kinase pathway
      plays an important role in various cellular functions, not only in vascular
      smooth muscle cell (VSMC) contraction but also in actin cytoskeleton
      organization, cell adhesion and motility, cytokinesis, and gene expressions, all
      of which may be involved in the pathogenesis of cardiovascular disease. At
      molecular level, Rho-kinase upregulates various molecules that accelerate
      inflammation/oxidative stress, thrombus formation, and fibrosis, whereas it
      downregulates endothelial nitric oxide synthase. The expression of Rho-kinase
      itself is mediated by protein kinase C/NF-kappaB pathway with an inhibitory and
      stimulatory modulation by estrogen and nicotine, respectively. At cellular level,
      Rho-kinase mediates VSMC hypercontraction, stimulates VSMC proliferation and
      migration, and enhances inflammatory cell motility. In animal studies, Rho-kinase
      has been shown to be substantially involved in the pathogenesis of vasospasm,
      arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary
      hypertension, stroke and heart failure, and to enhance central sympathetic nerve
      activity. Finally, in clinical studies, fasudil, a Rho-kinase inhibitor, is
      effective for the treatment of a wide range of cardiovascular disease, including
      cerebral and coronary vasospasm, angina, hypertension, pulmonary hypertension,
      and heart failure, with a reasonable safety. Thus, Rho-kinase is an important
      therapeutic target in cardiovascular medicine.

PMID- 16002742
TI  - Rapid effects of rosiglitazone treatment on endothelial function and inflammatory
      biomarkers.
AB  - BACKGROUND: Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or
      pioglitazone, improve endothelial function in patients with type 2 diabetes or
      metabolic syndrome, but it is currently unknown, whether these beneficial effects
      of TZDs depend on their metabolic action or may be caused by direct effects on
      the endothelium. Therefore, the present study examined whether short-term
      rosiglitazone treatment influences endothelium-dependent vasodilation as well as
      serum levels of vascular disease biomarkers in healthy, nondiabetic subjects.
      METHODS AND RESULTS: Short-term treatment (21 days) of healthy subjects (n = 10)
      did not significantly change blood glucose levels or lipid profile. In contrast,
      rosiglitazone significantly increased flow-mediated, endothelium-dependent
      vasodilation already within the first day from 5.3+/-2.7% at baseline to 7.8+/
      2.6%, further increasing it to 9.4+/-3.0% at day 21. In addition, the early
      improvement of endothelium-dependent vasodilation was paralleled by a rapid
      reduction of serum levels of the biomarkers C-reactive protein (CRP), serum
      amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers
      remained suppressed for the whole follow-up period of 7 days. In contrast,
      rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. CONCLUSIONS: Our
      study suggests a direct effect of TZD treatment on endothelial function and
      inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs,
      independent of their metabolic action, may exhibit protective effects in the
      vessel wall.

PMID- 16002743
TI  - Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia.
AB  - OBJECTIVE: Individuals with familial hypobetalipoproteinemia (FHBL) have been
      reported to be prone to fatty liver disease (FLD). Conversely, the profound
      reduction of low-density lipoprotein (LDL) cholesterol in this disorder might
      decrease cardiovascular risk. In the present study, we assessed hepatic steatosis
      as well as noninvasive surrogate markers for cardiovascular disease (CVD) in
      subjects with FHBL and in matched controls. METHODS AND RESULTS: Hepatic
      steatosis was assessed by abdominal ultrasonography. Carotid intima-media
      thickness (IMT) and distal common carotid arterial wall stiffness as surrogate
      markers for CVD risk were measured using high-resolution B-mode ultrasonography.
      Whereas transaminase levels were only modestly elevated, both prevalence (54%
      versus 29%; P=0.01) and severity of steatosis were significantly higher in FHBL
      individuals compared with controls. Despite similar IMT measurements, arterial
      stiffness was significantly lower in FHBL (P=0.04) compared with controls.
      Additionally, the increase in arterial stiffness as seen in the presence of
      traditional risk factors was attenuated, suggesting that very low levels of apoB
      containing lipoproteins can negate the adverse effects of other risk factors on
      the vasculature. CONCLUSIONS: FHBL is characterized by an increased prevalence
      and severity of fatty liver disease. The observed decreased level of arterial
      wall stiffness, most pronounced in the presence of nonlipid risk factors, is
      indicative of cardiovascular protection in these subjects.

PMID- 16002744
TI  - Dual serotonergic regulation of ventricular contractile force through 5-HT2A and
      5-HT4 receptors induced in the acute failing heart.
AB  - Cardiac responsiveness to neurohumoral stimulation is altered in congestive heart
      failure (CHF). In chronic CHF, the left ventricle has become sensitive to
      serotonin because of appearance of Gs-coupled 5-HT4 receptors. Whether this also
      occurs in acute CHF is unknown. Serotonin responsiveness may develop gradually or
      represent an early response to the insult. Furthermore, serotonin receptor
      expression could vary with progression of the disease. Postinfarction CHF was
      induced in male Wistar rats by coronary artery ligation with nonligated sham
      operated rats as control. Contractility was measured in left ventricular
      papillary muscles and mRNA quantified by real-time reverse-transcription PCR.
      Myosin light chain-2 phosphorylation was determined by charged gel
      electrophoresis and Western blotting. Ca2+ transients in CHF were measured in
      field stimulated fluo-4-loaded cardiomyocytes. A novel 5-HT2A receptor-mediated
      inotropic response was detected in acute failing ventricle, accompanied by
      increased 5-HT2A mRNA levels. Functionally, this receptor dominated over 5-HT4
      receptors that were also induced. The 5-HT2A receptor-mediated inotropic response
      displayed a triphasic pattern, shaped by temporally different activation of Ca2+
      calmodulin-dependent myosin light chain kinase, Rho-associated kinase and
      inhibitory protein kinase C, and was accompanied by increased myosin light chain
      2 phosphorylation. Ca2+ transients were slightly decreased by 5-HT2A stimulation.
      The acute failing rat ventricle is, thus, dually regulated by serotonin through
      Gq-coupled 5-HT2A receptors and Gs-coupled 5-HT4 receptors.

PMID- 16002745
TI  - Heterodimerization of beta1- and beta2-adrenergic receptor subtypes optimizes
      beta-adrenergic modulation of cardiac contractility.
AB  - Intermolecular interactions between members of both similar and divergent G
      protein-coupled receptor subfamilies have been shown in various experimental
      systems. Here, we demonstrate heterodimerization of predominant beta-adrenergic
      receptor (betaAR) subtypes expressed in the heart, beta1AR, and beta2AR, and its
      physiological relevance. In intact adult-mouse cardiac myocytes lacking native
      beta1AR and beta2AR, coexpression of both betaAR subtypes led to receptor
      heterodimerization, as evidenced by their coimmunoprecipitation, colocalization
      at optical resolution, and markedly increased binding affinity for subtype
      selective ligands. As a result, the dose-response curve of myocyte contraction to
      betaAR agonist stimulation with isoproterenol (ISO) was shifted leftward by
      approximately 1.5 orders of magnitude, and the response of cellular cAMP
      formation to ISO was enhanced concomitantly, indicating that intermolecular
      interactions of betaAR subtypes resulted in sensitization of these receptors in
      response to agonist stimulation. In contrast, the presence of beta1AR greatly
      suppressed ligand-independent spontaneous activity of coexisting beta2ARs. Thus,
      heterodimerization of beta1AR and beta2AR in intact cardiac myocytes creates a
      novel population of betaARs with distinct functional and pharmacological
      properties, resulting in enhanced signaling efficiency in response to agonist
      stimulation while silencing ligand-independent receptor activation, thereby
      optimizing beta-adrenergic modulation of cardiac contractility.

PMID- 16002746
TI  - Phospholemman-phosphorylation mediates the beta-adrenergic effects on Na/K pump
      function in cardiac myocytes.
AB  - Cardiac sympathetic stimulation activates beta-adrenergic (beta-AR) receptors and
      protein kinase A (PKA) phosphorylation of proteins involved in myocyte Ca
      regulation. The Na/K-ATPase (NKA) is essential in regulating intracellular [Na]
      ([Na]i), which in turn affects [Ca]i via Na/Ca exchange. However, how PKA
      modifies NKA function is unknown. Phospholemman (PLM), a member of the FXYD
      family of proteins that interact with NKA in various tissues, is a major PKA
      substrate in heart. Here we tested the hypothesis that PLM phosphorylation is
      responsible for the PKA effects on cardiac NKA function using wild-type (WT) and
      PLM knockout (PLM-KO) mice. We measured NKA-mediated [Na]i decline and current
      (IPump) to assess beta-AR effects on NKA function in isolated myocytes. In WT
      myocytes, 1 micromol/L isoproterenol (ISO) increased PLM phosphorylation and
      stimulated NKA activity mainly by increasing its affinity for internal Na (Km
      decreased from 18.8+/-1.4 to 13.6+/-1.5 mmol/L), with no significant effect on
      the maximum pump rate. This led to a significant decrease in resting [Na]i (from
      12.5+/-1.8 to 10.5+/-1.4 mmol/L). In PLM-KO mice under control conditions Km
      (14.2+/-1.5 mmol/L) was lower than in WT, but comparable to that for WT in the
      presence of ISO. Furthermore, ISO had no significant effect on NKA function in
      PLM-KO mice. ATPase activity in sarcolemmal vesicles also showed a lower Km(Na)
      in PLM-KO versus WT (12.9+/-0.9 versus 16.2+/-1.5). Thus, PLM inhibits NKA
      activity by decreasing its [Na]i affinity, and this inhibitory effect is relieved
      by PKA activation. We conclude that PLM modulates the NKA function in a manner
      similar to the way phospholamban affects the related SR Ca-ATPase (inhibition of
      transport substrate affinity, that is relieved by phosphorylation).

PMID- 16002747
TI  - Inhibition of lipopolysaccharide-induced inflammatory responses by an
      apolipoprotein AI mimetic peptide.
AB  - Previous studies suggest that high-density lipoprotein and apoAI inhibit
      lipopolysaccharide (LPS)-induced inflammatory responses. The goal of the current
      study was to test the hypothesis that the apoAI mimetic peptide L-4F exerts
      antiinflammatory effects similar to apoAI. Pretreatment of human umbilical vein
      endothelial cells (HUVECs) with LPS induced the adhesion of THP-1 monocytes.
      Incubation of cells with LPS and L-4F (1 to 50 microg/mL) reduced THP-1 adhesion
      in a concentration-dependent manner. This response was associated with a
      significant reduction in the synthesis of cytokines, chemokines, and adhesion
      molecules. L-4F reduced vascular cell adhesion molecule-1 expression induced by
      LPS or lipid A, whereas a control peptide (Sc-4F) showed no effect. In contrast
      to LPS treatment, L-4F did not inhibit IL-1beta- or tumor necrosis factor-alpha
      induced vascular cell adhesion molecule-1 expression. The inhibitory effect of L
      4F on LPS induction of inflammatory markers was associated with reduced binding
      of LPS to its plasma carrier molecule, lipopolysaccharide binding protein, and
      decreased binding of LPS to HUVEC monolayers. LPS and L-4F in HUVEC culture
      medium were fractionated by fast protein liquid chromatography and were localized
      to the same fractions, suggesting a physical interaction between these molecules.
      Proinflammatory responses to LPS are associated with the binding of lipid A to
      cell surface receptors. The current studies demonstrate that L-4F reduces the
      expression of inflammatory markers induced by LPS and lipid A and suggest that
      apoAI peptide mimetics may be useful in the treatment of inflammation associated
      with endotoxemia.

PMID- 16002748
TI  - Genome-wide screening for target regions of histone deacetylases in
      cardiomyocytes.
AB  - The acetylation status of core histones in cardiomyocytes has been linked to the
      development of cardiac hypertrophy and heart failure. Little is known, however,
      of the genes affected by abnormal histone acetylation in such pathological
      conditions. We recently developed a genome-wide screening method, differential
      chromatin scanning (DCS), to isolate genomic fragments associated with histones
      subject to differential acetylation. We have now applied DCS to H9C2 rat
      embryonic cardiomyocytes incubated with or without trichostatin A (TSA), a
      specific inhibitor of histone deacetylase (HDAC) activity. About 200 genomic
      fragments were readily isolated by DCS on the basis of the preferential
      acetylation of associated histones in TSA-treated cells. Quantitation of the
      amount of DNA in chromatin immunoprecipitates prepared with antibodies to
      acetylated histone H3 revealed that 37 of 38 randomly chosen DCS clones were
      preferentially precipitated from the TSA-treated cells, thus verifying the high
      fidelity of DCS. Epigenetic regulation of DCS clones was further confirmed in
      cells treated with sodium butyrate, another HDAC inhibitor, as well as in cardiac
      myocytes isolated from neonatal rats. The mRNA level of 9 (39%) of 23 genes
      corresponding to DCS clones changed in parallel with the level of histone
      acetylation in H9C2 cells. Furthermore, a physiological hypertrophic stimulus,
      cardiotrophin-1, affected the acetylation level of histones associated with
      genomic regions corresponding to certain DCS clones. Our data thus establish a
      genome-wide profile of HDAC targets in cardiomyocytes, which should provide a
      basis for further investigations into the role of epigenetic modification in
      cardiac disorders.

PMID- 16002749
TI  - Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1,
      a gene associated with pulmonary vascular disease.
AB  - Heightened expression of the S100 calcium-binding protein, S100A4/Mts1, is
      observed in pulmonary vascular disease. Loss of serotonin (5-hydroxytryptamine [5
      HT]) receptors or of the serotonin transporter (SERT) attenuates pulmonary
      hypertension in animals, and polymorphisms causing gain of SERT function are
      linked to clinical pulmonary vascular disease. Because 5-HT induces release of
      S100beta, we investigated the codependence of 5-HT receptors and SERT in
      regulating S100A4/Mts1 in human pulmonary artery smooth muscle cells (hPA-SMC). 5
      HT elevated S100A4/Mts1 mRNA levels and increased S100A4/Mts1 protein in hPA-SMC
      lysates and culture media. S100A4/Mts1 in the culture media stimulated
      proliferation and migration of hPA-SMC in a manner dependent on the receptor for
      advanced glycation end products. Treatment with SB224289 (selective antagonist of
      5-HT1B), fluoxetine (SERT inhibitor), SERT RNA-interference, and iproniazid
      (monoamine oxidase-A inhibitor), blocked 5-HT-induced S100A4/Mts1. 5-HT signaling
      mediated phosphorylation (p) of extracellular signal-regulated kinase 1/2
      (pERK1/2), but pERK1/2 nuclear translocation depended on SERT, monoamine oxidase
      activity, and reactive oxygen species. Nuclear translocation of pERK1/2 was
      required for pGATA-4-mediated transcription of S100A4/Mts1. These data provide
      evidence for a mechanistic link between the 5-HT pathway and S100A4/Mts1 in
      pulmonary hypertension and explain how the 5-HT1B receptor and SERT are
      codependent in regulating S100A4/Mts1.

PMID- 16002750
TI  - Transmural heterogeneity of Na+-Ca2+ exchange: evidence for differential
      expression in normal and failing hearts.
AB  - Spatial electrical heterogeneity has a profound effect on normal cardiac
      electrophysiology and genesis of cardiac arrhythmias in diseased hearts. The Na+
      Ca2+ exchanger (NCX) is a key linker, through Ca2+ signaling, between
      contractility and arrhythmias. Here we characterize the differential transmural
      expression of NCX in normal and rapid pacing-induced failing canine hearts.
      Significant transmural heterogeneity of NCX was present in normal hearts, as NCX
      current density measured at +80 mV was significantly (P<0.05) greater in
      epicardial (EPI) (5.49 pA/pF) than mid-myocardial (MID) (2.84 pA/pF) and
      endocardial (ENDO) (2.21 pA/pF) cells. Interestingly, heart failure caused a
      selective increase in NCX current density (P<0.05) limited to ENDO (by 202%) and
      MID (by 76%) but not EPI myocytes (P=not significant). The differences in
      functional expression were associated with changes in both mRNA and protein
      levels. The normal EPI layer exhibited the greatest NCX mRNA and protein levels
      compared with MID and ENDO layers, whereas the ENDO layer underwent the most
      pronounced increase in mRNA (by 185%) and protein (by 207%) levels in heart
      failure. The transmural NCX gradient, from EPI (greatest) to ENDO (least), is
      disrupted in heart failure. A selective upregulation of NCX expression in MID and
      ENDO in heart failure markedly redirects the orientation of the transmural
      functional gradient of NCX and may lead to enhanced vulnerability to cardiac
      arrhythmias.

PMID- 16002751
TI  - Role of Kv1 channels in control of arterial myogenic reactivity to intraluminal
      pressure.

PMID- 16002752
TI  - Letter in response to Bisoendial et al: "activation of inflammation and
      coagulation after infusion of C-reactive protein in humans".

PMID- 16002753
TI  - Control of adenosine transport by hypoxia.

PMID- 16002754
TI  - Pre-B-cell colony-enhancing factor regulates vascular smooth muscle maturation
      through a NAD+-dependent mechanism: recognition of a new mechanism for cell
      diversity and redox regulation of vascular tone and remodeling.

PMID- 16002756
TI  - "Clinical-CT mismatch" and the response to systemic thrombolytic therapy in acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Mismatch between clinical deficits and imaging lesions in
      acute stroke has been proposed as a method of identifying patients who have
      hypoperfused but still have viable brain, and may be especially apt to respond to
      reperfusion therapy. We explored this hypothesis using a combined database
      including 4 major clinical trials of intravenous (IV) thrombolytic therapy.
      METHODS: To determine what the radiological correlates of a "matched" functional
      deficit are, we calculated the relationship between the ASPECT score of the 24
      hour (follow-up) CT scan and the 24-hour National Institutes of Health Stroke
      Scale (NIHSS) score on the subsample with ASPECT scores performed at this time
      (n=820). Based on this empirical relationship, we computed the absolute
      difference between the observed baseline ASPECT score and the "expected" score
      (ie, matched) based on baseline NIHSS for all patients (n=2131). We tested
      whether patients with better than expected baseline ASPECTS were more likely to
      benefit from IV recombinant tissue plasminogen activation (rtPA). RESULTS: At 24
      hours, there was a strong, linear, negative correlation between NIHSS and ASPECTS
      (r2=0.33, P<0.0001); on average, an increase of 10 points on NIHSS corresponded
      to a decrease of approximately 3 points on ASPECTS. At baseline, the average
      degree of mismatch between the observed and "expected" ASPECTS was 2.1 points
      (interquartile range, 1.0 to 3.4). However, multiple analyses failed to reveal a
      consistent relationship between the degree of clinical-CT mismatch at baseline
      and a patient's likelihood of benefiting from IV rtPA. CONCLUSIONS: Clinical-CT
      mismatch using ASPECT scoring does not reliably identify patients more or less
      likely to benefit from IV rtPA.

PMID- 16002755
TI  - Custom design of the cardiac microenvironment with biomaterials.
AB  - Many strategies for repairing injured myocardium are under active investigation,
      with some early encouraging results. These strategies include cell therapies,
      despite little evidence of long-term survival of exogenous cells, and gene or
      protein therapies, often with incomplete control of locally-delivered dose of the
      factor. We propose that, ultimately, successful repair and regeneration
      strategies will require quantitative control of the myocardial microenvironment.
      This precision control can be engineered through designed biomaterials that
      provide quantitative adhesion, growth, or migration signals. Quantitative timed
      release of factors can be regulated by chemical design to direct cellular
      differentiation pathways such as angiogenesis and vascular maturation. Smart
      biomaterials respond to the local environment, such as protease activity or
      mechanical forces, with controlled release or activation. Most of these new
      biomaterials provide much greater flexibility for regenerating tissues ex vivo,
      but emerging technologies like self-assembling nanofibers can now establish
      intramyocardial cellular microenvironments by injection. This may allow
      percutaneous cardiac regeneration and repair approaches, or injectable-tissue
      engineering. Finally, materials can be made to multifunction by providing
      sequential signals with custom design of differential release kinetics for
      individual factors. Thus, new rationally-designed biomaterials no longer simply
      coexist with tissues, but can provide precision bioactive control of the
      microenvironment that may be required for cardiac regeneration and repair.

PMID- 16002757
TI  - Modeling the future burden of stroke in The Netherlands: impact of aging,
      smoking, and hypertension.
AB  - BACKGROUND AND PURPOSE: In the near future, the number of stroke patients and
      their related healthcare costs are expected to rise. The purpose of this study
      was to estimate this expected increase in stroke patients in the Netherlands. We
      sought to determine what the future developments in the number of stroke patients
      due to demographic changes and trends in the prevalence of smoking and
      hypertension in terms of the prevalence, incidence, and potential years of life
      lost might be. METHODS: A dynamic, multistate life table was used, which combined
      demographic projections and existing stroke morbidity and mortality data. It
      projected future changes in the number of stroke patients in several scenarios
      for the Dutch population for the period 2000 to 2020. The model calculated the
      annual number of new patients by age and sex by using incidence rates, defined by
      age, sex, and major risk factors. The change in the annual number of stroke
      patients is the result of incident cases minus mortality numbers. RESULTS:
      Demographic changes in the population suggest an increase of 27% in number of
      stroke patients per 1000 in 2020 compared with 2000. Extrapolating past trends in
      the prevalence of smoking behavior, hypertension, and stroke incidence resulted
      in an increase of 4%. CONCLUSIONS: The number of stroke patients in the
      Netherlands will rise continuously until the year 2020. Our study demonstrates
      that a large part of this increase in the number of patients is an inevitable
      consequence of the aging of the population.

PMID- 16002758
TI  - Taste disorders in acute stroke: a prospective observational study on taste
      disorders in 102 stroke patients.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to assess whether and how
      frequently patients with acute first-ever stroke exhibit gustatory dysfunction.
      METHODS: We performed a 1-year prospective observational study. Gustatory
      function was assessed using the standardized "taste strips" test. In addition, we
      assessed olfactory function, swallowing, stroke location, comorbidities, and the
      patients' medication. RESULTS: A total of 102 consecutive patients were enrolled
      (45 female, 57 male; mean age, 63 years); 31 of them (30%) exhibited gustatory
      loss and 7 (6%) had lateralized impairment of taste function. Predictors of
      impaired taste function were male gender (P=0.003), high National Institutes of
      Health Stroke Scale (NIHSS) score at admission (P=0.009), coexisting swallowing
      dysfunction (P=0.026), and a stroke of partial anterior circulation subtype
      (PACS) (P=0.008). In particular, in hypogeusic patients the lesion was most
      frequently localized in the frontal lobe (P=0.009). Follow-up examinations in 14
      patients indicated improvement of taste sensitivity. CONCLUSIONS: Taste disorders
      after stroke are frequent. A significant association was found for male gender,
      high NIHSS score, swallowing disorder, and PACS, particularly in the frontal
      lobe. Generally, taste disorders after stroke seem to have a good prognosis.

PMID- 16002759
TI  - Polymorphisms in genes of the endothelin system and cerebral small-vessel
      disease.
AB  - BACKGROUND AND PURPOSE: Endothelial dysfunction has been implicated in the
      pathogenesis of cerebral small-vessel disease (SVD). Endothelin (ET), released by
      the endothelium, plays a crucial role in vasoconstriction in the cerebral
      circulation and could contribute to the pathogenesis of cerebral SVD. Circulating
      ET levels may not reflect vascular production of endothelin-1 (ET-1), most of
      which is abluminal. Studying genetic associations, particularly of functional
      polymorphisms that alter activity of the ET system, is an attractive method of
      determining whether ET plays a role in SVD pathogenesis. We determined whether
      genetic variants in components of the ET system are a risk factor for cerebral
      SVD. METHODS: Three hundred SVD patients and 600 community controls were
      genotyped. Polymorphisms in the ET-1 gene (K198N), the ET receptor type A (ETA),
      (-231G>A and +1222C>T), and the ET type B (ETB) receptor (G57S and L277L) were
      genotyped. Polymorphisms were studied both individually and as haplotypes. With
      brain imaging, cases were subtyped into those with lacunar infarct without
      leukoaraiosis and those with leukoaraiosis. RESULTS: No significant differences
      were observed between SVD cases and controls for any individual single-nucleotide
      polymorphism or the ETA haplotype. There were no differences between cases with
      isolated lacunar infarct or with lacunar infarct and leukoaraiosis. CONCLUSIONS:
      This study, in a well-phenotyped population, does not support a role for genetic
      variation in the ET system as a risk factor for cerebral SVD.

PMID- 16002760
TI  - Serum ferritin is a risk factor for stroke in postmenopausal women.
AB  - BACKGROUND AND PURPOSE: Iron is an essential element for the human body. It has,
      however, been suggested that excessive iron stores may increase the risk of
      vascular disease. So far, epidemiologic studies on stroke are sparse. METHODS: We
      studied the association between iron status and stroke risk in a population-based
      cohort of 11 471 Dutch postmenopausal women between 49 and 70 years of age. Women
      were included between 1993 and 1997 and followed up until January 1, 2000, for
      cerebrovascular events. We conducted a case-cohort study by using all stroke
      cases (n=63) and a random sample of the baseline cohort (n=1134). Serum ferritin,
      serum iron, and transferrin saturation were measured as markers of iron status. A
      weighted Cox proportional-hazards model was used to estimate crude and
      multivariate-adjusted hazard ratios for tertiles of different iron parameters in
      relation to stroke. RESULTS: In a multivariate model, the highest tertile of
      serum ferritin concentration was associated with an increased risk of stroke
      (hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.87 to 2.42) compared
      with the lowest tertile. For ischemic stroke, the increase was more pronounced
      (HR, 2.23; 95% CI, 1.05 to 4.73) and reached statistical significance.
      CONCLUSIONS: Neither serum iron nor transferrin saturation was associated with an
      increased stroke risk. However, higher serum ferritin concentrations in
      postmenopausal women are associated with an increased risk of ischemic stroke.

PMID- 16002761
TI  - Acute hyperglycemia state is associated with lower tPA-induced recanalization
      rates in stroke patients.
AB  - BACKGROUND AND PURPOSE: Hyperglycemia (HG) has a deleterious effect in stroke
      patients by accelerating ischemic brain damage; moreover, its antifibrinolytic
      effect may also influence reperfusion. We aimed to study the effect of
      acute/chronic HG on tissue-type plasminogen activator (tPA)-induced
      recanalization. METHODS: We studied 139 consecutive stroke patients with
      documented intracranial artery occlusion treated with intravenous tissue-type
      plasminogen activator (tPA). Admission glucose levels were recorded (in mg/dL).
      The existence of previous chronic HG was determined by plasma levels of
      glycosylated hemoglobin (HbA1c, %) and fructosamine (in micromol/L). Transcranial
      Doppler monitoring assessed complete recanalization 2 hours after tPA bolus.
      National Institutes of Health Stroke Scale (NIHSS) scores were obtained at
      baseline and 48 hours. RESULTS: On admission, the median NIHSS score was 18 and
      mean glucose value was 140+/-63 mg/dL. At 2 hours, 32% of patients(n=44) achieved
      complete recanalization. Patients who recanalized showed lower admission glucose
      levels (127 vs 146 mg/dL; P=0.039) but no differences in HbA1c (6.3% vs 6.3%;
      P=0.896) or fructosamine (292 vs 293 micromol/L; P=0.957) were observed. Other
      variables associated with recanalization were initial distal middle cerebral
      artery occlusion (P=0.011) and platelet count (P=0.015). Patients with an
      admission glucose level >158 mg/dL had lower recanalization rates (16% vs 36.1%;
      P=0.035) and a higher NIHSS score at 48 hours (7 vs 14.5; P=0.04). After
      adjustment for stroke etiology, age, and risk factors, the only independent
      predictors on admission of no recanalization were glucose value >158 mg/dL (odds
      ratio [OR], 7.3; 95% confidence interval [CI], 1.3 to 42.3; P=0.027), proximal
      middle cerebral artery occlusion (OR, 2.6; 95% CI, 1.1 to 6.5; P=0.034), and
      platelet count <219,000/mL (OR, 2.6; 95% CI, 1.1 to 6.1; P=0.029). CONCLUSIONS:
      In tPA-treated patients, the acute but not chronic HG state may hamper the
      fibrinolytic process, delaying reperfusion of the ischemic penumbra. Early
      measures to reduce HG may favor early recanalization.

PMID- 16002762
TI  - New detected aneurysms on follow-up screening in patients with previously clipped
      intracranial aneurysms: comparison with DSA or CTA at the time of SAH.
AB  - BACKGROUND AND PURPOSE: Patients with a history of aneurysmal subarachnoid
      hemorrhage may have aneurysms on screening several years after the hemorrhage.
      For determining the benefits of follow-up screening, it is important to know
      whether these aneurysms have developed after the hemorrhage or are visible in
      retrospect, and if so, whether the size has increased. METHODS: Aneurysms were
      categorized into de novo aneurysms and aneurysms visible in retrospect (already
      present) with increased or stable size. We studied aneurysm characteristics for
      these 3 categories: the relation between aneurysm development or enlargement and
      duration of follow up and the relation between enlargement and initial size of
      the aneurysm. RESULTS: In 87 of 495 patients (17.6%), aneurysms were detected;
      for 51 of these patients with 62 aneurysms, the original catheter or computed
      tomographic angiogram was available for comparison. Of the 62 aneurysms, 19 were
      de novo and 43 were visible in retrospect, 10 with increased size and 33 with
      stable size. De novo aneurysms were mainly < or =5 mm (95%) and located at the
      middle cerebral artery (63%). For aneurysms visible in retrospect, the most
      frequent location was the posterior communicating artery (21%). There was no
      relation between the development of de novo aneurysms or enlargement and the
      duration of follow-up or between enlargement and the initial size of the
      aneurysm. CONCLUSIONS: Of aneurysms detected at screening, one third were de novo
      and two thirds were missed at the time of the initial hemorrhage. One quarter of
      initially small aneurysms had enlarged during follow-up.

PMID- 16002763
TI  - Association between alcohol consumption and subclinical carotid atherosclerosis:
      the Study of Health in Pomerania.
AB  - BACKGROUND AND PURPOSE: Epidemiologic studies have shown a J-shaped association
      between alcohol consumption and vascular diseases. However, only few studies have
      reported on the association between alcohol intake and subclinical
      atherosclerosis. The aim of the study was to investigate the relation between
      alcohol intake and carotid intima-media thickness (IMT) in participants of the
      population-based Study of Health in Pomerania. METHODS: In 1230 men and 1190
      women, the mean IMT of the right and left common carotid arteries was measured by
      B-mode ultrasonography. Alcohol consumption was assessed with a computer-assisted
      face-to-face interview. RESULTS: In men, carotid IMT as a function of alcohol
      intake was depicted as a J-shaped curve with a nadir for the alcohol intake
      category of 61 to 80 g/d. Linear regression models controlled for age, diabetes,
      systolic blood pressure, leisure time physical activity, food frequency patterns,
      smoking status, and education revealed a significant inverse association between
      IMT and alcohol intake < or =80 g/d in men (beta=-0.009, P<0.02), which became
      insignificant after further controlling for HDL cholesterol and fibrinogen (beta=
      0.007, P=NS). In women, neither a J-shaped relation nor significant differences
      in IMT between the drinking and nondrinking groups were found. CONCLUSIONS:
      Alcohol consumption is inversely correlated with carotid IMT in men but not in
      women. However, the total daily level of alcohol intake that shows a maximum
      protective effect against atherosclerosis is above the threshold where severe
      alcohol related comorbidity and organ damage have been reported.

PMID- 16002764
TI  - Carotid atherosclerotic plaque characteristics are associated with
      microembolization during carotid endarterectomy and procedural outcome.
AB  - BACKGROUND AND PURPOSE: During carotid endarterectomy (CEA), microemboli may
      occur, resulting in perioperative adverse cerebral events. The objective of the
      present study was to investigate the relation between atherosclerotic plaque
      characteristics and the occurrence of microemboli or adverse events during CEA.
      METHODS: Patients (n=200, 205 procedures) eligible for CEA were monitored by
      perioperative transcranial Doppler. The following phases were discriminated
      during CEA: dissection, shunting, release of the clamp, and wound closure. Each
      carotid plaque was stained for collagen, macrophages, smooth muscle cells,
      hematoxylin, and elastin. Semiquantitative analyses were performed on all
      stainings. Plaques were categorized into 3 groups based on overall appearance
      (fibrous, fibroatheromatous, or atheromatous). RESULTS: Fibrous plaques were
      associated with the occurrence of more microemboli during clamp release and wound
      closure compared with atheromatous plaques (P=0.04 and P=0.02, respectively).
      Transient ischemic attacks and minor stroke occurred in 5 of 205 (2.4%) and 6 of
      205 (2.9%) patients, respectively. Adverse cerebral outcome was significantly
      related to the number of microembolic events during dissection (P=0.003) but not
      during shunting, clamp release, or wound closure. More cerebrovascular adverse
      events occurred in patients with atheromatous plaques (7/69) compared with
      patients with fibrous or fibroatheromatous plaques (4/138) (P=0.04). CONCLUSIONS:
      Intraoperatively, a higher number of microemboli were associated with the
      presence of a fibrous but not an atheromatous plaque. However, atheromatous
      plaques were more prevalent in patients with subsequent immediate adverse events.
      In addition, specifically the number of microemboli detected during the
      dissection phase were related to immediate adverse events.

PMID- 16002765
TI  - Causes and predictors of death in cerebral venous thrombosis.
AB  - BACKGROUND AND PURPOSE: The causes of death of patients with cerebral venous
      thrombosis (CVT) have not been systematically addressed in previous studies. We
      aimed to analyze the causes and predictors of death during the acute phase of CVT
      in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) to
      identify preventable or treatable causes. METHODS: ISCVT is a multinational,
      prospective, observational study including 624 patients with CVT occurring
      between May 1998 and May 2001, in which 27 patients (4.3%) died during the acute
      phase, 21 (3.4%) within 30 days from symptom onset. Inclusion forms and a
      questionnaire assessing the causes of death were analyzed. A logistic regression
      analysis was performed to identify the predictors of death within 30 days from
      symptom onset of CVT. RESULTS: Median time between onset of symptoms and death
      was 13 days and between diagnosis and death, 5 days. Causes of death were mainly
      transtentorial herniation due to a unilateral focal mass effect (10 patients) or
      to diffuse edema and multiple parenchymal lesions (10 patients). Independent
      predictors of death were coma (odds ratio [OR], 8.8; 95% confidence interval
      [CI], 2.8 to 27.7), mental disturbance (OR, 2.5; 95% CI 0.9 to 7.3), deep CVT
      thrombosis (OR, 8.5; 95% CI, 2.6 to 27.8), right intracerebral hemorrhage (OR,
      3.4; 95% CI, 1.1 to 10.6), and posterior fossa lesion (OR, 6.5; 95% CI, 1.3 to
      31.7). Worsening of previous focal or de novo focal deficits increased the risk
      of death. CONCLUSIONS: The main causes of acute death were neurologic, the most
      frequent mechanism being transtentorial herniation.

PMID- 16002766
TI  - Stroke-induced neurogenesis in aged brain.
AB  - BACKGROUND AND PURPOSE: Stroke induced by middle cerebral artery occlusion (MCAO)
      triggers increased neurogenesis in the damaged striatum and nondamaged
      hippocampus of young adult rodents. We explored whether stroke influences
      neurogenesis similarly in the aged brain. METHODS: Young adult (3 months) and old
      (15 months) rats were subjected to 1 hour of MCAO, and new cells were labeled by
      intraperitoneal injection of 5-bromo-2'-deoxyuridine 5'-monophosphate (BrdU), a
      marker for dividing cells, for 2 weeks thereafter. Animals were euthanized at 7
      weeks after the insult, and neurogenesis was assessed immunocytochemically with
      antibodies against BrdU and neuronal markers with epifluorescence or confocal
      microscopy. RESULTS: Young and old rats exhibited the same increased numbers of
      new striatal neurons after stroke, despite basal cell proliferation in the
      subventricular zone being reduced in the aged brain. In contrast, both the number
      of stroke-generated granule cells and basal neurogenesis in the dentate
      subgranular zone were lower in old compared with young animals. Also, the ability
      of newly formed cells to differentiate into neurons was impaired in the aged
      dentate gyrus. CONCLUSIONS: Basal neurogenesis is impaired in the subgranular and
      subventricular zones of aged animals, but both regions react to stroke with
      increased formation of new neurons. The magnitude of striatal neurogenesis after
      stroke is similar in young and old animals, indicating that this potential
      mechanism for self-repair also operates in the aged brain.

PMID- 16002767
TI  - Effects of moderate-velocity strength training on peak muscle power and movement
      velocity: do women respond differently than men?
AB  - The effects of a 10-wk unilateral knee extension strength training (ST) program
      on peak power (PP) and peak movement velocity (PV), at given absolute (force
      load) and relative (same % of 1 repetition maximum) resistances (loads), were
      examined in 30 older men [64 yr (7 SD)] and 32 older women [62 yr (6 SD)]. PP
      increased significantly in both men and women at the same absolute (P < 0.001)
      and relative loads (P < 0.01) with ST. Men had a significantly greater increase
      in relative PP than women with ST at 60% (P < 0.01) and 70% (P < 0.001) of 1
      repetition maximum when covarying for baseline differences and age. However, when
      each subject was tested at the same absolute load and when PP was normalized for
      the muscle volume of the trained knee extensors (i.e., absolute muscle power
      quality), women increased by 9% (P < 0.05), whereas men did not change. Both men
      and women increased their absolute PV (P < 0.001) but decreased their relative PV
      significantly with ST (P < 0.05). However, when baseline values and age were
      covaried, women had significantly less of a decrease in relative PV quality with
      ST than men (P < 0.01), although the difference was small. These normalized data
      suggest that ST-induced increases in PP depend on muscular hypertrophy in men,
      but not in women, providing further support for the hypothesis developed from our
      previous report (Ivey FM, Tracy BL, Lemmer JT, NessAiver M, Metter EJ, Fozard JL
      and Hurley BF. J Gerontol A Biol Sci Med Sci 55: B152-B157, 2000) that
      improvements in muscle function with ST result from nonmuscle mass adaptations to
      a greater extent in women than men.

PMID- 16002768
TI  - NaHCO3-induced alkalosis reduces the phosphocreatine slow component during heavy
      intensity forearm exercise.
AB  - During heavy-intensity exercise, the mechanisms responsible for the continued
      slow decline in phosphocreatine concentration ([PCr]) (PCr slow component) have
      not been established. In this study, we tested the hypothesis that a reduced
      intracellular acidosis would result in a greater oxidative flux and,
      consequently, a reduced magnitude of the PCr slow component. Subjects (n = 10)
      performed isotonic wrist flexion in a control trial and in an induced alkalosis
      (Alk) trial (0.3g/kg oral dose of NaHCO3, 90 min before testing). Wrist flexion,
      at a contraction rate of 0.5 Hz, was performed for 9 min at moderate- (75% of
      onset of acidosis; intracellular pH threshold) and heavy-intensity (125%
      intracellular pH threshold) exercise. 31P-magnetic resonance spectroscopy was
      used to measure intracellular [H+], [PCr], [Pi], and [ATP]. The initial recovery
      data were used to estimate the rate of ATP synthesis and oxidative flux at the
      end of heavy-intensity exercise. In repeated trials, venous blood sampling was
      used to measure plasma [H+], [HCO3-], and [Lac-]. Throughout rest and exercise,
      plasma [H+] was lower (P < 0.05) and [HCO3-] was elevated (P < 0.05) in Alk
      compared with control. During the final 3 min of heavy-intensity exercise, Alk
      caused a lower (P < 0.05) intracellular [H+] [246 (SD 117) vs. 291 nmol/l (SD
      129)], a greater (P < 0.05) [PCr] [12.7 (SD 7.0) vs. 9.9 mmol/l (SD 6.0)], and a
      reduced accumulation of [ADP] [0.065 (SD 0.031) vs. 0.098 mmol/l (SD 0.059)].
      Oxidative flux was similar (P > 0.05) in the conditions at the end of heavy
      intensity exercise. In conclusion, our results are consistent with a reduced
      intracellular acidosis, causing a decrease in the magnitude of the PCr slow
      component. The decreased PCr slow component in Alk did not appear to be due to an
      elevated oxidative flux.

PMID- 16002769
TI  - Age-related changes in ATP-producing pathways in human skeletal muscle in vivo.
AB  - Energy for muscle contractions is supplied by ATP generated from 1) the net
      hydrolysis of phosphocreatine (PCr) through the creatine kinase reaction, 2)
      oxidative phosphorylation, and 3) anaerobic glycolysis. The effect of old age on
      these pathways is unclear. The purpose of this study was to examine whether age
      may affect ATP synthesis rates from these pathways during maximal voluntary
      isometric contractions (MVIC). Phosphorus magnetic resonance spectroscopy was
      used to assess high-energy phosphate metabolite concentrations in skeletal muscle
      of eight young (20-35 yr) and eight older (65-80 yr) men. Oxidative capacity was
      assessed from PCr recovery after a 16-s MVIC. We determined the contribution of
      each pathway to total ATP synthesis during a 60-s MVIC. Oxidative capacity was
      similar across age groups. Similar rates of ATP synthesis from PCr hydrolysis and
      oxidative phosphorylation were observed in young and older men during the 60-s
      MVIC. Glycolytic flux was higher in young than older men during the 60-s
      contraction (P < 0.001). When expressed relative to the overall ATP synthesis
      rate, older men relied on oxidative phosphorylation more than young men (P =
      0.014) and derived a smaller proportion of ATP from anaerobic glycolysis (P <
      0.001). These data demonstrate that although oxidative capacity was unaltered
      with age, peak glycolytic flux and overall ATP production from anaerobic
      glycolysis were lower in older men during a high-intensity contraction. Whether
      this represents an age-related limitation in glycolytic metabolism or a
      preferential reliance on oxidative ATP production remains to be determined.

PMID- 16002770
TI  - Hemodynamic and autonomic changes induced by Ironman: prediction of competition
      time by blood pressure variability.
AB  - We hypothesized that the extreme endurance exercise of an Ironman competition
      would lead to long-standing hemodynamic and autonomic changes. We investigated
      also the possibility of predicting competition performance from baseline
      hemodynamic and autonomic parameters. We have investigated 27 male athletes
      before competition, 1 h after, and then for the following week after the
      competition. The Task Force monitor was used to measure beat-to-beat hemodynamic
      and autonomic parameters during supine rest and active standing. Heart rate (P <
      0.001) was increased, and stroke index (P = 0.011), systolic blood pressure (P =
      0.004), diastolic blood pressure (P < 0.001), total peripheral resistance index
      (P < 0.001), and baroreceptor reflex sensitivity (P < 0.001) were decreased after
      the competition. The 0.05- to 0.17-Hz band of heart rate and blood pressure
      variability was increased (P < 0.001 and P < 0.001, respectively), the 0.17- to
      0.40-Hz band of heart rate interval variability was decreased after the
      competition (P < 0.001). All parameters returned to baseline values 3 days after
      the competition. After the competition, the autonomic response to orthostasis was
      significantly impaired. The 0.05- to 0.17-Hz band of diastolic blood pressure
      variability before competition and weekly net exercise training, but not the
      other hemodynamic and autonomic parameters, were related to competition time in
      multivariate regression analysis (multiple r = 0.70, P < 0.001). The marked
      hemodynamic and autonomic changes after an ultraendurance race, which are
      compatible with myocardial depression in the face of sympathetic activation and
      reduction of afterload, return to baseline after only 1-3 days. Because the 0.05-
      to 0.17-Hz band of diastolic blood pressure variability contributes to the
      prediction of competition time, the analysis of blood pressure variability in the
      frequency domain deserves further study for the prediction of endurance capacity.

PMID- 16002771
TI  - Acute and chronic cardiovascular effects of intermittent hypoxia in C57BL/6J
      mice.
AB  - We investigated the effects of 1) acute hypoxia and 2) 5 wk of chronic
      intermittent hypoxia (IH) on the systemic and pulmonary circulations of C57BL/6J
      mice. Mice were chronically instrumented with either femoral artery or right
      ventricular catheters. In response to acute hypoxia (4 min of 10% O2; n = 6),
      systemic arterial blood pressure fell (P < 0.005) from 107.7 +/- 2.5 to 84.7 +/-
      6.5 mmHg, whereas right ventricular pressure increased (P < 0.005) from 11.7 +/-
      0.8 to 14.9 +/- 1.3 mmHg. Another cohort of mice was then exposed to IH for 5 wk
      (O2 nadir = 5%, 60-s cycles, 12 h/day) and then implanted with catheters. In
      response to 5 wk of chronic IH, mice (n = 8) increased systemic blood pressure by
      7.5 mmHg, left ventricle + septum weight by 32.2 +/- 7.5 x 10(-2) g/100 g body wt
      (P < 0.015), and right ventricle weight by 19.3 +/- 3.2 x 10(-2) g/100 g body wt
      (P < 0.001), resulting in a 14% increase in the right ventricle/left ventricle +
      septum weight (P < 0.005). We conclude that in C57BL/6J mice 1) acute hypoxia
      causes opposite effects on the pulmonary and systemic circulations, leading to
      preferential loading of the right heart; and 2) chronic IH in mice results in
      mild to moderate systemic and pulmonary hypertension, with resultant left- and
      right-sided ventricular hypertrophy.

PMID- 16002772
TI  - NADPH oxidase p22phox gene variants are associated with systemic oxidative stress
      biomarker responses to exercise training.
AB  - Systemic oxidative stress plays a role in many degenerative diseases. Although
      regular physical activity has been known as the most effective nonpharmacological
      intervention to alleviate the oxidative stress, the beneficial effect varies
      between individuals. We investigated whether NADPH oxidase p22phox gene C242T and
      A640G polymorphisms are associated with systemic oxidative stress level response
      to exercise training (ExTr). Fifty-nine sedentary middle-aged to older Caucasians
      with relatively high cardiovascular disease risk factors underwent a 6-mo
      standardized ExTr program. Body mass index, plasma lipoprotein-lipid profiles,
      cardiovascular fitness, and plasma thiobarbituric acid reactive substances
      (TBARS) were measured before and after ExTr. Demographic and initial levels of
      cardiovascular disease risk factors were similar among genotype groups for both
      polymorphisms. Overall, TBARS was decreased by 16% with ExTr in the entire group
      (P < 0.001). There was no significant difference in TBARS changes with ExTr among
      the C242T genotype groups. However, A allele carriers showed greater reduction in
      TBARS than noncarriers at the A640G locus (P = 0.05). There was a significant
      interaction (P = 0.05) between ExTr and A640G polymorphism in TBARS changes with
      ExTr. This interaction remained after accounting for age and baseline TBARS
      level. Furthermore, diplotype analysis showed that TBARS was decreased to a
      greater extent in the C242/A640 haplotype carriers compared with the noncarriers
      (P < 0.05). We found that p22phox polymorphisms, especially A640G, were
      associated with differential changes in systemic oxidative stress with aerobic
      exercise training.

PMID- 16002773
TI  - Subcellular responses of p53 and Id2 in fast and slow skeletal muscle in response
      to stretch-induced overload.
AB  - Tumor suppressor p53 and inhibitor of DNA-binding/differentiation Id2 were
      examined after 7 or 21 days of wing weighting in fast patagialis (PAT) and slow
      anterior latissimus dorsi (ALD) wing muscles of young adult and old Japanese
      quails. The contralateral wing served as the intra-animal control. Seven days of
      loading increased PAT and ALD muscle weight by 28 and 96%, respectively, in young
      birds. PAT and ALD muscle weight was 49 and 179% greater, respectively, than
      control muscles after 21 days of loading in young birds. In aged birds, no PAT or
      ALD hypertrophy was found after 7 days of loading; however, PAT and ALD muscle
      weight increased by 29 and 102%, respectively, after 21 days of loading. Id2
      protein in the nuclear muscle fraction increased in both PAT and ALD muscles from
      young adult and old birds that were loaded for 7 days and in ALD muscles after 21
      days of loading relative to contralateral control muscles. Nuclear p53 protein
      was greater in 7- or 21-day loaded PAT and ALD muscles relative to control
      muscles in both age groups. Cytosolic Id2 and p53 protein contents were not
      changed in loaded PAT or ALD muscles relative to control muscles at any time
      point. These data suggest that nuclear, but not cytosolic, Id2 and p53 are
      responsive to stretch-induced muscle overload. Moreover, the attenuated ability
      of the aged skeletal muscle to achieve hypertrophy does not appear to be
      explained by the subcellular changes in Id2 and p53 content with overload.

PMID- 16002774
TI  - Exercise flow-volume loops in prepubescent aerobically trained children.
AB  - We studied mechanical ventilatory constraints in 13 aerobically trained (Tr) and
      11 untrained (UT) prepubescent children by plotting the exercise flow-volume (F
      V) loops within the maximal F-V loop (MFVL) measured at rest. The MFVL allowed to
      determine forced vital capacity (FVC) and maximal expiratory flows. Expiratory
      and inspiratory reserve volumes relative to FVC (ERV/FVC and IRV/FVC,
      respectively) were measured during a progressive exercise test until exhaustion.
      Breathing reserve (BR) and expiratory flow limitation (expFL), expressed in
      percentage of tidal volume (V(T)) and defined as the part of the tidal breath
      meeting the boundary of the MFVL, were measured. Higher FVC and maximal
      expiratory flows were found in Tr than UT (P < 0.05) at rest. Our results have
      shown that during exercise, excepting one subject, all Tr regulated their V(T)
      within FVC similarly during exercise, by breathing at low lung volume at the
      beginning of exercise followed breathing at high lung volume at strenuous
      exercise. In UT, ERV/FVC and IRV/FVC were regulated during exercise in many ways.
      The proportion of children who presented an expFL was nearly the same in both
      groups (approximately 70% with a range of 14 to 65% of V(T)), and no significant
      difference was found during exercise concerning expFL. However, higher
      ventilation (V(E)), ERV/FVC, and dyspnea associated with lower BR, IRV/FVC, and
      SaO2 were reported at peak power in Tr than UT (P < 0.05). These results suggest
      that, because of their higher Ve level, trained children presented higher
      ventilatory constraints than untrained. These may influence negatively the SaO2
      level and dyspnea during strenuous exercise.

PMID- 16002775
TI  - Tumor necrosis factor-alpha and malnutrition-induced inhibition of diaphragm
      fiber growth in young rats.
AB  - Tumor necrosis factor (TNF)-alpha has been implicated in several muscle-wasting
      disorders, with increased levels of the cytokine reported in malnourished
      children. The role of TNF-alpha in mediating malnutrition-induced inhibition of
      diaphragm (DIA) muscle growth in young growing rats was evaluated. Three groups
      of rats were studied: 1) control (CTL); 2) nutritional deprivation (ND; 50% of
      normal food intake for 7 days); and 3) ND + rat specific anti-TNF-alpha antibody.
      DIA fiber cross-sectional areas were determined. Serum and muscle TNF-alpha
      levels were measured by real-time PCR, ELISA, and immunohistochemistry. Body
      weights decreased 20% in ND rats and increased 46% in CTL animals. Anti-TNF-alpha
      had no effect on body weight or on DIA mass in ND animals. ND significantly
      reduced cross-sectional areas of all fiber types (33-46%). Anti-TNF-alpha failed
      to attenuate ND-induced inhibition of DIA fiber growth. Serum TNF-alpha levels
      increased 2.6-fold in ND animals, with levels suppressed to below CTL values with
      anti-TNF-alpha. DIA TNF-alpha mRNA and protein levels increased two- to threefold
      in ND rats. Anti-TNF-alpha antibodies suppressed muscle levels of the cytokine in
      ND animals to near CTL values. TNF-alpha immunoreactivity in all DIA fibers
      revealed similar directions of change in both ND groups. Direction and magnitude
      of change in DIA phosphorylated p38 MAPK (a likely second messenger of TNF-alpha)
      tracked those of TNF-alpha. Muscle levels of IGF-I mRNA and phosphorylated Akt
      were markedly reduced in ND animals with no change following anti-TNF-alpha
      therapy. Thus rat anti-TNF-alpha at a dose known to neutralize the cytokine
      failed to attenuate or reverse ND-induced inhibition of DIA fiber growth in our
      model.

PMID- 16002776
TI  - Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study
      of exercise intensity and amount.
AB  - Despite the importance of randomized, dose-response studies for proper evaluation
      of effective clinical interventions, there have been no dose-response studies on
      the effects of exercise amount on abdominal obesity, a major risk factor for
      metabolic syndrome, diabetes, and cardiovascular disease. One hundred seventy
      five sedentary, overweight men and women with mild to moderate dyslipidemia were
      randomly assigned to participate for 6 mo in a control group or for approximately
      8 mo in one of three exercise groups: 1) low amount, moderate intensity,
      equivalent to walking 12 miles/wk (19.2 km) at 40-55% of peak oxygen consumption;
      2) low amount, vigorous intensity, equivalent to jogging 12 miles/wk at 65-80% of
      peak oxygen consumption; or 3) high amount, vigorous intensity, equivalent to
      jogging 20 miles/wk (32.0 km). Computed tomography scans were analyzed for
      abdominal fat. Controls gained visceral fat (8.6 +/- 17.2%; P = 0.001). The
      equivalent of 11 miles of exercise per week, at either intensity, prevented
      significant accumulation of visceral fat. The highest amount of exercise resulted
      in decreased visceral (-6.9 +/- 20.8%; P = 0.038) and subcutaneous (-7.0 +/-
      10.8%; P < 0.001) abdominal fat. Significant gains in visceral fat over only 6 mo
      emphasize the high cost of continued inactivity. A modest exercise program,
      consistent with recommendations from the Centers for Disease Control/American
      College of Sports Medicine (CDC/ACSM), prevented significant increases in
      visceral fat. Importantly, a modest increase over the CDC/ACSM exercise
      recommendations resulted in significant decreases in visceral, subcutaneous, and
      total abdominal fat without changes in caloric intake.

PMID- 16002777
TI  - Relationship between force and stiffness in muscle fibers after stretch.
AB  - The purpose of this study was to evaluate the relationship between force and
      stiffness after stretch of activated fibers, while simultaneously changing
      contractility by interfering with the cross-bridge kinetics and muscle
      activation. Single fibers dissected from lumbrical muscles of frogs were placed
      at a length 20% longer than the plateau of the force-length relationship,
      activated, and stretched by 5 and 10% of fiber length (speed: 40% fiber
      length/s). Experiments were conducted with maximal and submaximal stimulation in
      Ringer solution and with the addition of 2 and 5 mM of the myosin inhibitor 2,3
      butanedione monoxime (BDM) to the solution. The steady-state force after stretch
      of an activated fiber was higher than the isometric force produced at the
      corresponding length in all conditions investigated. Lowering the frequency of
      stimulation decreased the force and stiffness during isometric contractions, but
      it did not change force enhancement and stiffness enhancement after stretch.
      Administration of BDM decreased the force and stiffness during isometric
      contractions, but it increased the force enhancement and stiffness enhancement
      after stretch. The relationship between force enhancement and stiffness suggests
      that the increase in force after stretch may be caused by an increase in the
      proportion of cross bridges attached to actin. Because BDM places cross bridges
      in a weakly bound, pre-powerstroke state, our results further suggest that force
      enhancement is partially associated with a recruitment of weakly bound cross
      bridges into a strongly bound state.

PMID- 16002778
TI  - Heart rate variability and spontaneous baroreflex sequences in supine healthy
      volunteers subjected to nasal positive airway pressure.
AB  - To determine the dynamic effects of short-term nasal positive airway pressure
      (nPAP) on cardiovascular autonomic control, continuous recordings of
      noninvasively obtained hemodynamic measurements and heart rate variability (HRV)
      were obtained in 10 healthy subjects during frequency-controlled breathing
      (between 0.20 and 0.24 Hz) in supine posture under different pressures of nPAP
      ranging from 3 to 20 cmH(2)O. HRV was assessed using spectral analysis of the R-R
      interval. The slope of the regression line between spontaneous systolic blood
      pressure and pulse interval changes was taken as an index of the sensitivity of
      arterial baroreflex modulation of heart rate (sequence method). Application of
      nPAP resulted in a pressure-dependent decrease of cardiac output and stroke
      volume (P < 0.05, ANOVA) and in an increase in total peripheral resistance (P <
      0.03, ANOVA). Hemodynamic changes under increasing nPAP were accompanied by a
      decrease in total power of HRV despite mean R-R interval remaining unchanged. The
      overall decrease in HRV was accompanied by a reduction across all frequency bands
      when absolute units were used (P < 0.01). When the power of low frequency and
      high frequency was calculated in normalized units, a diminished high frequency
      and an increased low-to-high frequency ratio were observed (P < 0.05). Compared
      with low levels of nPAP, pressure levels of >10 cmH(2)O were associated with a
      significant decline in the mean slope of spontaneous baroreceptor sequences (P <
      0.04). These findings indicate that short-term administration of nPAP in normal
      subjects exerts significant alterations in R-R interval variability and
      spontaneous baroreflex modulation of heart rate.

PMID- 16002779
TI  - Contribution of the ABC transporters Bcrp1 and Mdr1a/1b to the side population
      phenotype in mammary gland and bone marrow of mice.
AB  - The ability of cells to export Hoechst 33342 can be used to identify a
      subpopulation of cells (side population [SP]) with characteristics of stem cells
      in many tissues. The ATP-binding cassette transporters Bcrp1 (Abcg2) and Mdr1a/1b
      (Abcb1a/1b) have been implicated as being responsible for this phenotype. To
      further explore the involvement of these transporters in the SP phenotype, we
      have generated Bcrp1/Mdr1a/1b triple knockout mice and studied the effect of
      their absence on the SP in bone marrow and mammary gland. Whereas in bone marrow
      Bcrp1 was almost exclusively responsible for the SP, both transporters
      contributed to the SP phenotype in the mammary gland, where their combined
      absence resulted in a nearly complete loss of SP. Interestingly, bone marrow of
      Mdr1a/1b-/- mice frequently displayed an elevated SP, which was reversible by the
      Bcrp1 inhibitor Ko143, suggesting that Bcrp1 can compensate for the loss of
      Mdr1a/1b in bone marrow.

PMID- 16002780
TI  - Three-dimensional perfusion culture of human bone marrow cells and generation of
      osteoinductive grafts.
AB  - Three-dimensional (3D) culture systems are critical to investigate cell
      physiology and to engineer tissue grafts. In this study, we describe a simple yet
      innovative bioreactor-based approach to seed, expand, and differentiate bone
      marrow stromal cells (BMSCs) directly in a 3D environment, bypassing the
      conventional process of monolayer (two-dimensional [2D]) expansion. The system,
      based on the perfusion of bone marrow-nucleated cells through porous 3D
      scaffolds, supported the formation of stromal-like tissues, where BMSCs could be
      cocultured with hematopoietic progenitor cells in proportions dependent on the
      specific medium supplements. The resulting engineered constructs, when implanted
      ectopically in nude mice, generated bone tissue more reproducibly, uniformly, and
      extensively than scaffolds loaded with 2D-expanded BMSCs. The developed system
      may thus be used as a 3D in vitro model of bone marrow to study interactions
      between BMSCs and hematopoietic cells as well as to streamline manufacture of
      osteoinductive grafts in the context of regenerative medicine.

PMID- 16002781
TI  - Activation of transforming growth factor-beta1/p38/Smad3 signaling in stromal
      cells requires reactive oxygen species-mediated MMP-2 activity during bone marrow
      damage.
AB  - Dose-escalated chemotherapy has proven utility in a variety of treatment
      settings, including preparative regimens before bone marrow or hematopoietic stem
      cell transplantation. However, the potential damage imposed by aggressive
      regimens on the marrow microenvironment warrants further investigation. In the
      present study, we tested the hypothesis that dose-escalated chemotherapy, with
      etoposide as a model chemotherapeutic agent, activates the transforming growth
      factor beta-1 (TGF-beta1) signaling pathway in bone marrow stromal cells. After
      high-dose etoposide exposure in vitro, Smad3 protein was phosphorylated in a time
      and dose-dependent manner in marrow-derived stromal cells, coincident with the
      release of active and latent TGF-beta1 from the extracellular matrix.
      Phosphorylation was modulated by p38 kinase, with translocation of Smad3 from the
      cytoplasm to the nucleus subsequent to its phosphorylation. Etoposide induced
      activation of TGF-beta1 followed the generation of reactive oxygen species and
      required matrix metalloproteinase-2 (MMP-2) protein availability. Chemotherapy
      effects were diminished in MMP-2(-/-) knockout stromal cells and TGF-beta1
      knockdown small interfering RNA-transfected stromal cells, in which
      phosphorylation of Smad3 was negligible after etoposide exposure. Stable
      transfection of a human MMP-2 cDNA into bone marrow stromal cells resulted in
      elevated phosphorylation of Smad3 during chemotherapy. These data suggest TGF
      beta1/p38/Smad3 signaling cascades are activated in bone marrow stromal cells
      after dose-escalated chemotherapy and may contribute to chemotherapy-induced
      alterations of the marrow microenvironment.

PMID- 16002782
TI  - Defining the role of Wnt/beta-catenin signaling in the survival, proliferation,
      and self-renewal of human embryonic stem cells.
AB  - We used a panel of human and mouse fibroblasts with various abilities for
      supporting the prolonged growth of human embryonic stem cells (hESCs) to
      elucidate growth factors required for hESC survival, proliferation, and
      maintenance of the undifferentiated and pluripotent state (self-renewal). We
      found that supportive feeder cells secrete growth factors required for both hESC
      survival/proliferation and blocking hESC spontaneous differentiation to achieve
      self-renewal. The antidifferentiation soluble factor is neither leukemia
      inhibitory factor nor Wnt, based on blocking experiments using their antagonists.
      Because Wnt/beta-catenin signaling has been implicated in cell-fate determination
      and stem cell expansion, we further examined the effects of blocking or adding
      recombinant Wnt proteins on undifferentiated hESCs. In the absence of feeder cell
      derived factors, hESCs cultured under a feeder-free condition
      survived/proliferated poorly and gradually differentiated. Adding recombinant
      Wnt3a stimulated hESC proliferation but also differentiation. After 4-5 days of
      Wnt3a treatment, hESCs that survived maintained the undifferentiated phenotype
      but few could form undifferentiated hESC colonies subsequently. Using a
      functional reporter assay, we found that the beta-catenin-mediated
      transcriptional activation in the canonical Wnt pathway was minimal in
      undifferentiated hESCs, but greatly upregulated during differentiation induced by
      the Wnt treatment and several other methods. Thus, Wnt/beta-catenin activation
      does not suffice to maintain the undifferentiated and pluripotent state of hESCs.
      We propose a new model for the role of Wnt/beta-catenin signaling in
      undifferentiated hESCs.

PMID- 16002783
TI  - Differentiation of human embryonic stem cells to neural lineages in adherent
      culture by blocking bone morphogenetic protein signaling.
AB  - Human embryonic stem cells (hESCs) have extensive self-renewal capacity and are
      competent to differentiate into any cell type of the body. They are valuable not
      only for the study of early human development but also for regenerative medicine.
      However, how to direct differentiation of hESCs along a particular lineage
      pathway to a specific cell type remains a challenge. Although hESCs have been
      shown to differentiate in vitro into neural progenitors, the factors controlling
      their differentiation are poorly understood. In this study, we report the
      development of an in vitro adherent culture system to efficiently generate neural
      progenitors in which neither multicellular aggregates nor stromal cells are
      required. We show that inhibition of bone morphogenetic protein signaling by its
      antagonist noggin is sufficient to block extraembryonic cell fate, transiently
      sustain Oct4 gene expression, and result in robust production of neural
      progenitors. Our findings will provide a platform for studying the molecular
      mechanism controlling neural differentiation.

PMID- 16002784
TI  - A universal BMV-based RNA recombination system--how to search for general rules
      in RNA recombination.
AB  - At present, there is no doubt that RNA recombination is one of the major factors
      responsible for the generation of new RNA viruses and retroviruses. Numerous
      experimental systems have been created to investigate this complex phenomenon.
      Consequently, specific RNA structural motifs mediating recombination have been
      identified in several viruses. Unfortunately, up till now a unified model of
      genetic RNA recombination has not been formulated, mainly due to difficulties
      with the direct comparison of data obtained for different RNA-based viruses. To
      solve this problem, we have attempted to construct a universal system in which
      the recombination activity of various RNA sequences could be tested. To this end,
      we have used brome mosaic virus, a model (+)RNA virus of plants, for which the
      structural requirements of RNA recombination are well defined. The effectiveness
      of the new homomolecular system has been proven in an experiment involving two
      RNA sequences derived from the hepatitis C virus genome. In addition, comparison
      of the data obtained with the homomolecular system with those generated earlier
      using the heteromolecular one has provided new evidence that the mechanisms of
      homologous and non-homologous recombination are different and depend on the
      virus' mode of replication.

PMID- 16002785
TI  - DNA microarrays on nanoscale-controlled surface.
AB  - We have developed new surface to ensure a proper spacing between immobilized
      biomolecules. While DNA microarray on this surface provided each probe DNA with
      ample space for hybridization with incoming target DNAs, the microarray showed
      enhanced discrimination efficiency for various types of single nucleotide
      polymorphism. The high discrimination efficiency holds for all tested cases
      (100:<1 for internal mismatched cases; 100:<28 for terminal mismatched ones). In
      addition, by investigating influence of hybridization temperature and washing
      condition on the fluorescence intensity and the discrimination efficiency with
      and without controlled mesospacing, it was observed that the nanoscale-controlled
      surface showed good discrimination efficiency in a wide range of temperature (37
      50 degrees C), and hybridization behavior on the surface was in agreement with
      the solution one. Intriguingly, it was found that washing process after the
      hybridization was critical for the high discrimination efficiency. For the
      particular case, washing process was so efficient that only 30 s washing was
      sufficient to reach the optimal discrimination ratio.

PMID- 16002787
TI  - A novel method of screening thrombin-inhibiting DNA aptamers using an evolution
      mimicking algorithm.
AB  - Thrombin-inhibiting DNA aptamers have already been obtained through the
      systematic evolution of ligands by exponential enrichment (SELEX). However, SELEX
      is a method that screens DNA aptamers that bind to their target molecules, and it
      sometimes fails to screen good inhibitors. Therefore, it is necessary to develop
      a method of screening DNA aptamers based on their inhibitory effects on the
      target molecules. We developed a novel method of detecting aptamers using an
      evolution-mimicking algorithm, and we applied it to the search of new aptamers
      which inhibit thrombin. First, we randomly designed and synthesized ten 15mer
      oligonucleotides presumed to form G-quartet structures, and then measured their
      thrombin-inhibiting activities. The aptamers showing high inhibitory activity
      were selected, and we shuffled and mutated those sequences in silico to generate
      10 new sequences of next-generation aptamers. After repeating the cycle five
      times, we successfully obtained the same aptamers reported previously, and they
      showed high inhibitory activity. In addition, we added 8mer oligonucleotides to
      both the 5' and the 3' end of the selected 15mer aptamers, and then repeated the
      evolution in silico. After two cycles, we were able to obtain aptamers with
      higher inhibitory activity than that of the 15mer aptamers.

PMID- 16002786
TI  - A novel mammalian expression system derived from components coordinating nicotine
      degradation in arthrobacter nicotinovorans pAO1.
AB  - We describe the design and detailed characterization of 6-hydroxy-nicotine
      (6HNic)-adjustable transgene expression (NICE) systems engineered for lentiviral
      transduction and in vivo modulation of angiogenic responses. Arthrobacter
      nicotinovorans pAO1 encodes a unique catabolic machinery on its plasmid pAO1,
      which enables this Gram-positive soil bacterium to use the tobacco alkaloid
      nicotine as the exclusive carbon source. The 6HNic-responsive repressor-operator
      (HdnoR-O(NIC)) interaction, controlling 6HNic oxidase production in
      A.nicotinovorans pAO1, was engineered for generic 6HNic-adjustable transgene
      expression in mammalian cells. HdnoR fused to different transactivation domains
      retained its O(NIC)-binding capacity in mammalian cells and reversibly adjusted
      transgene transcription from chimeric O(NIC)-containing promoters (P(NIC); O(NIC)
      fused to a minimal eukaryotic promoter [P(min)]) in a 6HNic-responsive manner.
      The combination of transactivators containing various transactivation domains
      with promoters differing in the number of operator modules as well as in their
      relative inter-O(NIC) and/or O(NIC)-P(min) spacing revealed steric constraints
      influencing overall NICE regulation performance in mammalian cells. Mice
      implanted with microencapsulated cells engineered for NICE-controlled expression
      of the human glycoprotein secreted placental alkaline phosphatase (SEAP) showed
      high SEAP serum levels in the absence of regulating 6HNic. 6HNic was unable to
      modulate SEAP expression, suggesting that this nicotine derivative exhibits
      control-incompatible pharmacokinetics in mice. However, chicken embryos
      transduced with HIV-1-derived self-inactivating lentiviral particles transgenic
      for NICE-adjustable expression of the human vascular endothelial growth factor
      121 (VEGF121) showed graded 6HNic response following administration of different
      6HNic concentrations. Owing to the clinically inert and highly water-soluble
      compound 6HNic, NICE-adjustable transgene control systems may become a welcome
      alternative to available drug-responsive homologs in basic research, therapeutic
      cell engineering and biopharmaceutical manufacturing.

PMID- 16002788
TI  - Stable transmission of targeted gene modification using single-stranded
      oligonucleotides with flanking LNAs.
AB  - Targeted mutagenesis directed by oligonucleotides (ONs) is a promising method for
      manipulating the genome in higher eukaryotes. In this study, we have compared
      gene editing by different ONs on two new target sequences, the eBFP and the rd1
      mutant photoreceptor betaPDE cDNAs, which were integrated as single copy
      transgenes at the same genomic site in 293T cells. Interestingly, antisense ONs
      were superior to sense ONs for one target only, showing that target sequence can
      by itself impart strand-bias in gene editing. The most efficient ONs were short
      25 nt ONs with flanking locked nucleic acids (LNAs), a chemistry that had only
      been tested for targeted nucleotide mutagenesis in yeast, and 25 nt ONs with
      phosphorothioate linkages. We showed that LNA-modified ONs mediate dose-dependent
      target modification and analyzed the importance of LNA position and content.
      Importantly, when using ONs with flanking LNAs, targeted gene modification was
      stably transmitted during cell division, which allowed reliable cloning of
      modified cells, a feature essential for further applications in functional
      genomics and gene therapy. Finally, we showed that ONs with flanking LNAs aimed
      at correcting the rd1 stop mutation could promote survival of photoreceptors in
      retinas of rd1 mutant mice, suggesting that they are also active in vivo.

PMID- 16002789
TI  - DNA looping induced by a transcriptional enhancer in vivo.
AB  - Enhancers are DNA sequences that can activate gene transcription from remote
      positions. In yeast, regulatory sequences that are functionally equivalent to the
      metazoan enhancers are called upstream activating sequences (UASs). UASs show a
      lower degree of flexibility than their metazoan counterparts, but can
      nevertheless activate transcription from a distance of >1000 bp from the
      promoter. One of several models for the mechanism of action of transcriptional
      enhancers proposes that enhancer-bound activating proteins contact promoter-bound
      transcription factors and thereby get in close proximity to the promoter region
      with concomitant looping of the intervening DNA. We tested the mode of enhancer
      activity in yeast. A polymerase II-transcribed gene was paired with a remote,
      inducible enhancer. An independent reporter system was inserted next to the
      promoter to monitor the potential modes of enhancer activity. Our results show
      that the enhancer activated the reporter system only in the presence of a
      functional promoter. We also demonstrate that the heterologous expression of
      GAGA, a factor known to facilitate DNA loop formation, allows enhancer action in
      yeast over a distance of 3000 bp.

PMID- 16002790
TI  - Mammalian enzymes for preventing transcriptional errors caused by oxidative
      damage.
AB  - 8-Oxo-7,8-dihydroguanine (8-oxoGua) is produced in cells by reactive oxygen
      species normally formed during cellular metabolic processes. This oxidized base
      can pair with both adenine and cytosine, and thus the existence of this base in
      messenger RNA would cause translational errors. The MutT protein of Escherichia
      coli degrades 8-oxoGua-containing ribonucleoside di- and triphosphates to the
      monophosphate, thereby preventing the misincorporation of 8-oxoGua into RNA.
      Here, we show that for human the MutT-related proteins, NUDT5 and MTH1 have the
      ability to prevent translational errors caused by oxidative damage. The increase
      in the production of erroneous proteins by oxidative damage is 28-fold over the
      wild-type cells in E.coli mutT deficient cells. By the expression of NUDT5 or
      MTH1 in the cells, it is reduced to 1.4- or 1.2-fold, respectively. NUDT5 and
      MTH1 hydrolyze 8-oxoGDP to 8-oxoGMP with V(max)/K(m) values of 1.3 x 10(-3) and
      1.7 x 10(-3), respectively, values which are considerably higher than those for
      its normal counterpart, GDP (0.1-0.5 x 10(-3)). MTH1, but not NUDT5, possesses an
      additional activity to degrade 8-oxoGTP to the monophosphate. These results
      indicate that the elimination of 8-oxoGua-containing ribonucleotides from the
      precursor pool is important to ensure accurate protein synthesis and that both
      NUDT5 and MTH1 are involved in this process in human cells.

PMID- 16002791
TI  - The satiating power of protein--a key to obesity prevention?

PMID- 16002792
TI  - Alcohol, methylenetetrahydrofolate 677C->T genotype, and low folate intake:
      concurrent causes for hyperhomocysteinemia.

PMID- 16002793
TI  - Interactive effects of iron and zinc on biochemical and functional outcomes in
      supplementation trials.
AB  - Iron and zinc are essential micronutrients for human health. Deficiencies in
      these 2 nutrients remain a global problem, especially among women and children in
      developing countries. Supplementation with iron and zinc as single micronutrients
      enhances distinct and unique biochemical and functional outcomes. These
      micronutrients have the potential to interact when given together; thus, it is
      important to assess the biochemical and functional evidence from clinical trials
      before supplementation policies are established. We reviewed randomized trials
      that assessed the effects of iron and zinc supplementation on iron and zinc
      status. On the basis of this review, zinc supplementation alone does not appear
      to have a clinically important negative effect on iron status. However, when zinc
      is given with iron, iron indicators do not improve as greatly as when iron is
      given alone. In most of the studies, iron supplementation did not affect the
      biochemical status of zinc, but the data are not clear regarding morbidity
      outcomes. Although some trials have shown that joint iron and zinc
      supplementation has less of an effect on biochemical or functional outcomes than
      does supplementation with either mineral alone, there is no strong evidence to
      discourage joint supplementation. Supplementation programs that provide iron and
      zinc together are an efficient way to provide both micronutrients, provided the
      benefits of individual supplementation are not lost. Further research is needed
      before health policies on joint supplementation programs can be established.

PMID- 16002794
TI  - Association of physical activity with body-composition indexes in children aged 6
      8 y at varied risk of obesity.
AB  - BACKGROUND: Physical inactivity increases the risk of obesity, but the relations
      between reported levels of physical activity (PA) and measures of body fatness
      (BF) in children are remarkably inconsistent. OBJECTIVE: We examined the relation
      between objective measures of PA and body-composition indexes in nonobese
      children. DESIGN: A cross-sectional study was conducted in 100 children aged 6-8
      y who were recruited according to their risk of future obesity: high-risk
      children had >/=1 obese parent [body mass index (BMI; in kg/m(2)): >30] and low
      risk children had 2 nonobese biological parents (BMI: <30). Free-living activity
      energy expenditure (AEE) and PA level were calculated from 7-d doubly labeled
      water measurements, time spent in light-intensity activity was assessed by heart
      rate monitoring, and body composition was determined from isotopic dilution. To
      adjust for body size, fat mass and fat-free mass were normalized for height and
      expressed as fat mass index (FMI) and lean mass index (LMI), respectively.
      RESULTS: High-risk children had significantly higher BMI, LMI, and FMI than did
      low-risk children, but no group differences in PA were found. AEE and PA level
      were positively associated with LMI and, after adjustment for sex and fat-free
      mass, negatively associated with FMI but not with BMI. Boys who spent more than
      the median time in light-intensity activities had significantly higher FMI than
      did less sedentary boys. This difference was not observed in girls. CONCLUSIONS:
      AEE and PA level were negatively associated with BF in nonobese children.
      Accurate measures of body composition are essential to appropriate assessment of
      relations between PA and obesity risk.

PMID- 16002795
TI  - Resting metabolic rate is an important predictor of serum adiponectin
      concentrations: potential implications for obesity-related disorders.
AB  - BACKGROUND: Little is known about the regulation of adiponectin. Animal studies
      suggest local regulation by adipocytokines or alterations in energy expenditure,
      and studies in humans suggest regulation by alcohol intake and ethnicity.
      OBJECTIVE: To identify regulators of adiponectin in humans, we measured resting
      metabolic rate (RMR), serum adiponectin, glucose, insulin, triacylglycerol,
      alcohol intake, and anthropometric indexes in 457 white patients with overweight
      or obesity. DESIGN: A cross-sectional design was used, and multivariate
      regression analysis was performed with adiponectin as the dependent variable and
      potential predictors as independent variables. RESULTS: Simple linear analyses
      showed significant associations between adiponectin and sex, with a standardized
      coefficient of -0.38 (women compared with men) and an explanation of variation of
      the model (R(2)) of 14%; age (0.21; 4%); RMR (-0.52; 27%); fat-free mass (-0.40;
      16%); fat mass (-0.16; 2%); visceral fat (-0.24; 6%; computed tomography at L4
      L5); fasting triacylglycerol (-0.28; 8%); and insulin resistance (-0.38; 14%;
      homeostasis model assessment). Adiponectin and alcohol were not associated (
      0.04; 0%). Multivariate analyses, which allowed adjustment for confounding,
      showed that RMR is the most important predictor of adiponectin (-0.31; 29%),
      followed successively by insulin resistance (-0.16; 31%; model containing RMR and
      insulin resistance), fat mass (0.20; 34%), age (0.34; 35%), visceral fat (-0.34;
      40%), and fasting triacylglycerol (-0.12, 41%). CONCLUSIONS: Low resting
      metabolism (RMR) is associated with high serum adiponectin. We speculate that
      subjects with low RMR, who are theoretically at greater risk of obesity-related
      disorders, are especially protected by adiponectin.

PMID- 16002796
TI  - Folic acid supplementation for 3 wk reduces pulse pressure and large artery
      stiffness independent of MTHFR genotype.
AB  - BACKGROUND: Folic acid reduces plasma homocysteine and may be an important
      therapy for preventing cardiovascular disease. A key mechanism may be the
      reduction of arterial stiffness. OBJECTIVE: The effect of folic acid
      supplementation on blood pressure and large artery stiffness was examined in
      relation to methylenetetrahydrofolate reductase (MTHFR) genotype. DESIGN: Forty
      one asymptomatic men with normal or high-normal ambulatory blood pressure
      (systolic: >130 to <145 mm Hg; diastolic: >80 to <90 mm Hg) participated. The
      study had a randomized, placebo-controlled, double-blind, crossover design that
      incorporated 3-wk treatments with 5 mg folic acid/d or matching placebo; each
      treatment was separated by a 4-wk washout phase. RESULTS: Folic acid reduced
      brachial pulse pressure by 4.7 +/- 1.6 mm Hg (P < 0.05) without changing mean
      arterial pressure. Systemic arterial compliance increased by 0.15 +/- 0.03 mL/mm
      Hg (P < 0.05) after folic acid treatment but did not change after placebo
      treatment. These responses did not significantly correlate with either
      homocysteine or folate plasma concentrations. MTHFR genotype CC homozygotes
      (without the 677C-->T polymorphism) with normal blood pressure had a larger
      reduction in homocysteine concentrations in response to folic acid than did T
      allele carriers. Blood pressure and arterial stiffness responses were independent
      of MTHFR genotype. CONCLUSION: Folic acid is a safe and effective supplement that
      targets large artery stiffness and may prevent isolated systolic hypertension.

PMID- 16002797
TI  - Functional foods for coronary heart disease risk reduction: a meta-analysis using
      a multivariate approach.
AB  - BACKGROUND: It has been difficult to identify the appropriate bioactive substance
      for the development of new functional foods associated with coronary heart
      disease, because the results of many clinical studies are contradictory.
      OBJECTIVE: The objective of this study was to use the multivariate statistical
      approach known as principal component analysis (PCA) followed by a mixed model to
      process data obtained from a meta-analysis aimed at evaluating simultaneously the
      effect of ingestion of 1 of 3 types of bioactive substances (n-3 fatty acids,
      soluble fibers, and phytosterols) on 1 or more of 4 biomarkers (plasma total
      cholesterol, triacylglycerol, LDL cholesterol, and HDL cholesterol). DESIGN: Five
      independent variables (number of patients per study, dose, age, body mass index,
      and treatment length) and 4 dependent variables (percentage change in blood total
      cholesterol, LDL, HDL, and triacylglycerol) from 159 studies and substudies were
      organized into a matrix. The original values were converted to linear correlation
      units, which resulted in a new matrix. RESULTS: Two principal components were
      enough to explain 63.73% and 84.27% of the variance in the independent and
      dependent variables, respectively. Phytosterols and soluble fibers had a
      hypocholesterolemic effect, whereas n-3 fatty acids lowered triacylglycerol and
      increased total, LDL, and HDL cholesterol. The PCA and mixed model showed that
      this behavior was independent of dose, number of patients per study, age, and
      body mass index but was associated with treatment length. CONCLUSIONS: PCA is
      useful for summarizing available scientific information in examinations of health
      claims for foods and supplements.

PMID- 16002798
TI  - A high-protein diet induces sustained reductions in appetite, ad libitum caloric
      intake, and body weight despite compensatory changes in diurnal plasma leptin and
      ghrelin concentrations.
AB  - BACKGROUND: Ad libitum, low-carbohydrate diets decrease caloric intake and cause
      weight loss. It is unclear whether these effects are due to the reduced
      carbohydrate content of such diets or to their associated increase in protein
      intake. OBJECTIVE: We tested the hypothesis that increasing the protein content
      while maintaining the carbohydrate content of the diet lowers body weight by
      decreasing appetite and spontaneous caloric intake. DESIGN: Appetite, caloric
      intake, body weight, and fat mass were measured in 19 subjects placed
      sequentially on the following diets: a weight-maintaining diet (15% protein, 35%
      fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat,
      and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and
      50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet
      phase to measure the area under the plasma concentration versus time curve (AUC)
      for insulin, leptin, and ghrelin. RESULTS: Satiety was markedly increased with
      the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (+/-SE)
      spontaneous energy intake decreased by 441 +/- 63 kcal/d, body weight decreased
      by 4.9 +/- 0.5 kg, and fat mass decreased by 3.7 +/- 0.4 kg with the ad libitum,
      high-protein diet, despite a significantly decreased leptin AUC and increased
      ghrelin AUC. CONCLUSIONS: An increase in dietary protein from 15% to 30% of
      energy at a constant carbohydrate intake produces a sustained decrease in ad
      libitum caloric intake that may be mediated by increased central nervous system
      leptin sensitivity and results in significant weight loss. This anorexic effect
      of protein may contribute to the weight loss produced by low-carbohydrate diets.

PMID- 16002799
TI  - Bioelectrical impedance analysis: population reference values for phase angle by
      age and sex.
AB  - BACKGROUND: Phase angle is an indicator based on reactance and resistance
      obtained from bioelectrical impedance analysis (BIA). Although its biological
      meaning is still not clear, phase angle appears to have an important prognostic
      role. OBJECTIVE: The aim of this study was to estimate population averages and
      SDs of phase angle that can be used as reference values. DESIGN: BIA and other
      methods used to evaluate body composition, including hydrodensitometry and total
      body water, were completed in 1967 healthy adults aged 18-94 y. Phase angle was
      calculated directly from body resistance and reactance, and fat mass (FM) was
      estimated from the combination of weight, hydrodensitometry, and total body water
      by using the 3-compartment Siri equation. Phase angle values were compared across
      categories of sex, age, body mass index (BMI), and percentage FM. RESULTS: Phase
      angle was significantly (P < 0.001) smaller in women than in men and was lower
      with greater age (P < 0.001). Phase angle increased with an increase in BMI and
      was significantly inversely associated with percentage fat in men. Phase angle
      was significantly predicted from sex, age, BMI, and percentage FM in multiple
      regression models. CONCLUSIONS: Phase angle differs across categories of sex,
      age, BMI, and percentage fat. These reference values can serve as a basis for
      phase angle evaluations in the clinical setting.

PMID- 16002800
TI  - Body composition and mortality in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Survival studies have consistently shown significantly greater
      mortality rates in underweight and normal-weight patients with chronic
      obstructive pulmonary disease (COPD) than in overweight and obese COPD patients.
      OBJECTIVE: To compare the contributions of low fat-free mass and low fat mass to
      mortality, we assessed the association between body composition and mortality in
      COPD. DESIGN: We studied 412 patients with moderate-to-severe COPD [Global
      Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stages II-IV, forced
      expiratory volume in 1 s of 36 +/- 14% of predicted (range: 19-70%). Body
      composition was assessed by using single-frequency bioelectrical impedance. Body
      mass index, fat-free mass index, fat mass index, and skeletal muscle index were
      calculated and related to recently developed reference values. COPD patients were
      stratified into defined categories of tissue-depletion pattern. Overall mortality
      was assessed at the end of follow-up. RESULTS: Semistarvation and muscle atrophy
      were equally distributed among disease stages, but the highest prevalence of
      cachexia was seen in GOLD stage IV. Forty-six percent of the patients (n = 189)
      died during a maximum follow-up of 5 y. Cox regression models, with and without
      adjustment for disease severity, showed that fat-free mass index (relative risk:
      0.90; 95% CI: 0.84, 0.96; P = 0.003) was an independent predictor of survival,
      but fat mass index was not. Kaplan-Meier and Cox regression plots for cachexia
      and muscle atrophy did not differ significantly. CONCLUSIONS: Fat-free mass is an
      independent predictor of mortality irrespective of fat mass. This study supports
      the inclusion of body-composition assessment as a systemic marker of disease
      severity in COPD staging.

PMID- 16002801
TI  - Patterns of bioelectrical impedance vector distribution by body mass index and
      age: implications for body-composition analysis.
AB  - BACKGROUND: Bioelectrical impedance analysis (BIA) gives resistance (R) and
      reactance (Xc). R and Xc normalized for body height (H) can be plotted as a
      bivariate vector (H(2)/Xc versus H(2)/R). Vector BIA is useful for studying the
      determinants of BIA results. OBJECTIVE: We investigated the effect of age on BIA
      results and its relevance to body-composition analysis in a large database of
      impedance vector distributions stratified by age, sex, and body mass index (BMI).
      DESIGN: Mean bivariate vector distribution patterns (95% confidence ellipses)
      were examined in a German population of 15605 children and adolescents and 213294
      adults. Children and adolescents were divided into 3 age groups with up to 5 BMI
      categories. In adults, 5 BMI categories were stratified into 7 age groups.
      RESULTS: Mean impedance vectors were shorter in children than in adults. The
      vector distribution pattern was influenced by sex, BMI, and age, with shorter
      vectors in females than in males and longer vectors with increasing BMI.
      Consistent with a decrease in body cell mass with increasing age, there was a
      downward slope in the mean vector with age as a result of a decrease in the
      H(2)/Xc vector component. By contrast, there was no age-dependent increase in the
      H(2)/R vector component. In women of the same BMI at different ages, H(2)/R and
      percentage fat mass tended to decrease with age. CONCLUSIONS: The lack of an age
      dependent increase in the H(2)/R vector component renders conventional BIA
      unsuitable for an examination of the age-related increase in body fat mass. By
      contrast, the increase in the H(2)/Xc vector component with advancing age
      suggests the potential of BIA to depict the age-related decrease in body cell
      mass.

PMID- 16002802
TI  - Effect of whey on blood glucose and insulin responses to composite breakfast and
      lunch meals in type 2 diabetic subjects.
AB  - BACKGROUND: Whey proteins have insulinotropic effects and reduce the postprandial
      glycemia in healthy subjects. The mechanism is not known, but insulinogenic amino
      acids and the incretin hormones seem to be involved. OBJECTIVE: The aim was to
      evaluate whether supplementation of meals with a high glycemic index (GI) with
      whey proteins may increase insulin secretion and improve blood glucose control in
      type 2 diabetic subjects. DESIGN: Fourteen diet-treated subjects with type 2
      diabetes were served a high-GI breakfast (white bread) and subsequent high-GI
      lunch (mashed potatoes with meatballs). The breakfast and lunch meals were
      supplemented with whey on one day; whey was exchanged for lean ham and lactose on
      another day. Venous blood samples were drawn before and during 4 h after
      breakfast and 3 h after lunch for the measurement of blood glucose, serum
      insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like
      peptide 1 (GLP-1). RESULTS: The insulin responses were higher after both
      breakfast (31%) and lunch (57%) when whey was included in the meal than when whey
      was not included. After lunch, the blood glucose response was significantly
      reduced [-21%; 120 min area under the curve (AUC)] after whey ingestion.
      Postprandial GIP responses were higher after whey ingestion, whereas no
      differences were found in GLP-1 between the reference and test meals.
      CONCLUSIONS: It can be concluded that the addition of whey to meals with rapidly
      digested and absorbed carbohydrates stimulates insulin release and reduces
      postprandial blood glucose excursion after a lunch meal consisting of mashed
      potatoes and meatballs in type 2 diabetic subjects.

PMID- 16002803
TI  - Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate
      improves plasma glucose disposal in patients with type 2 diabetes.
AB  - BACKGROUND: Although insulin secretion after carbohydrate ingestion is severely
      impaired in patients with type 2 diabetes, amino acid and protein co-ingestion
      can substantially increase plasma insulin responses. OBJECTIVE: We investigated
      insulin responses and the subsequent plasma glucose disposal rates after the
      ingestion of carbohydrate alone (CHO) or with a protein hydrolysate and amino
      acid mixture (CHO+PRO) in patients with a long-term diagnosis of type 2 diabetes.
      DESIGN: Ten type 2 diabetic patients [mean (+/-SEM) age: 62 +/- 2 y; body mass
      index (kg/m(2)): 27 +/- 1] and 9 healthy control subjects (age: 58 +/- 1 y; body
      mass index: 27 +/- 1) participated in 2 trials in which the plasma insulin
      response was measured after the ingestion of 0.7 g carbohydrate . kg(-1) . h(-1)
      with or without 0.35 g . kg(-1) . h(-1) of a mixture that contained a protein
      hydrolysate, leucine, and phenylalanine. Continuous infusions with [6,6
      (2)H(2)]glucose were then given to investigate plasma glucose disposal. RESULTS:
      Plasma insulin responses were higher by 299 +/- 64% and 132 +/- 63% in the
      CHO+PRO trial than in the CHO trial in the diabetic patients and the matched
      control subjects, respectively (P < 0.001). The subsequent plasma glucose
      responses were reduced by 28 +/- 6% and 33 +/- 3% in the CHO+PRO trial than in
      the CHO trial in the diabetic patients and the matched control subjects,
      respectively (P < 0.001). The reduced plasma glucose response in the diabetic
      patients was attributed to a 13 +/- 3% increase in glucose disposal (P < 0.01).
      CONCLUSIONS: The combined ingestion of carbohydrate with a protein hydrolysate
      and amino acid mixture significantly increases de novo insulin production in
      patients with a long-term diagnosis of type 2 diabetes. The increased insulin
      response stimulates plasma glucose disposal and reduces postprandial glucose
      concentrations.

PMID- 16002804
TI  - Absorption of calcium from tortilla meals prepared from low-phytate maize.
AB  - BACKGROUND: Calcium fortification of maize has been achieved for millennia in
      Central America by the process of nixtamalization. Bioavailability of calcium is,
      however, compromised by phytate, which is present in large quantities in maize
      kernels and is only modestly reduced by nixtamalization. OBJECTIVE: The objective
      was to compare the absorption of calcium from tortilla meals prepared from low
      phytate maize with that from meals prepared from maize with typical phytate
      content. DESIGN: At 1-mo intervals, 5 healthy adult women were fed 2 test meals
      of approximately 140 g tortillas in lieu of breakfast. On one occasion, the
      tortillas were prepared from maize with approximately 60% phytate reduction, and,
      on the other occasion, they were prepared from the matching isohybrid wild-type
      maize. Beginning midway through the test meal, (44)Ca (0.3 mg/kg body wt) was
      administered in water as an extrinsic label; (42)Ca (0.06 mg/kg body wt) was
      administered intravenously immediately after the test meal. Isotope ratios of
      (42)Ca to (43)Ca and of (44)Ca to (43)Ca were measured by inductively coupled
      plasma mass spectrometry in urine collected as an 8-h pool from the period 16-24
      h after intravenous tracer administration and prepared by the oxalate
      precipitation method. Fractional absorption of calcium was determined by using a
      dual-isotope ratio technique. RESULTS: Mean fractional absorption of calcium from
      tortillas prepared from the low-phytate maize (0.50 +/- 0.03) was significantly
      (P = 0.003) greater than that from tortillas prepared from the control maize
      (0.35 +/- 0.07). CONCLUSION: The increase in the quantity of calcium absorbed
      could be of practical importance for calcium nutriture when the intake of dairy
      products is limited.

PMID- 16002805
TI  - Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral
      doses of a lutein supplement.
AB  - BACKGROUND: Adequate intake of lutein is postulated to reduce the risk of age
      related macular degeneration, but kinetic information for developing a dosing
      regimen is sparse. OBJECTIVE: The objective was to characterize lutein plasma
      kinetics in a multiple dosing design and to assess the effects of lutein intake
      on concentrations of other plasma carotenoids. DESIGN: After a run-in period of 7
      d, 19 healthy volunteers were assigned to receive daily oral doses of 4.1 mg
      lutein (n = 8; group 1) or 20.5 mg lutein (n = 8; group 2) for 42 d or no lutein
      (n = 3; control group). The supplement contained 8.3% zeaxanthin relative to
      lutein (100%). The time profiles of plasma xanthophyll concentrations were
      monitored over the dosing phase, and samples were collected frequently on day 42
      and for 24 d after dosing. RESULTS: Average plasma all-E-lutein concentrations
      increased from 0.14 to 0.52 +/- 0.13 and 1.45 +/- 0.69 micromol/L in groups 1 and
      2, respectively. Dose-normalized lutein bioavailability in group 2 was
      approximately 60% of that in group 1. Kinetic disposition half-life did not
      differ significantly between groups. On average, dosing for 18 d was required to
      reach a >90% fraction of the steady state concentration, which is consistent with
      an effective half-life for accumulation of approximately 5.6 d. Plasma kinetics
      of all-E-lutein were paralleled by those of all-E-3-dehydro-lutein. Kinetic
      analysis indicated formation of all-E-3-dehydro-lutein from lutein. Lutein was
      well tolerated and did not affect the concentrations of other carotenoids.
      CONCLUSION: Long-term supplementation with 4.1 and 20.5 mg lutein as beadlets
      increased plasma lutein concentrations approximately 3.5- and 10-fold,
      respectively.

PMID- 16002806
TI  - Long-term calcium supplementation does not affect the iron status of 12-14-y-old
      girls.
AB  - BACKGROUND: Single-meal studies have established that calcium has an acute
      inhibitory effect on the absorption of iron. However, there is growing evidence
      that high calcium intakes do not compromise iron status. OBJECTIVE: We evaluated
      whether long-term calcium supplementation taken with the main meal affected
      biomarkers of iron status in adolescent girls with high requirements of both iron
      and calcium. DESIGN: The study was a randomized, double-blind, placebo-controlled
      trial of supplementation with 500 mg Ca/d for 1 y among 113 adolescent girls aged
      13.2 +/- 0.4 y at enrollment. Participants were advised to take the supplement
      with their evening meal, which usually contributes the majority of dietary iron.
      Iron status was assessed at baseline and after 1 y of supplementation by
      measuring hemoglobin and serum concentrations of ferritin and transferrin
      receptors (TfRs). RESULTS: The mean (+/-SD) hemoglobin at enrollment was 134 +/-
      9 g/L, geometric mean serum ferritin was 26.3 microg/L (interquartile range: 18.6
      39.4 microg/L), and serum TfR was 4.19 mg/L (3.52-5.10 mg/L). Daily calcium
      supplementation had no effect on the least-squares mean concentrations of iron
      status markers adjusted for their baseline values (hemoglobin: 136 and 134 g/L, P
      = 0.31; ferritin: 25.4 and 26.1 microg/L, P = 0.73; TfR: 4.1 and 4.4 mg/L, P =
      0.12; and the ratio of TfR to ferritin: 160 and 161 in the calcium and placebo
      groups, respectively; P = 0.97). CONCLUSION: Although it remains to be shown in
      iron-deficient persons, long-term iron status does not seem to be compromised by
      high calcium intakes.

PMID- 16002807
TI  - Long-term moderate zinc supplementation increases exchangeable zinc pool masses
      in late-middle-aged men: the Zenith Study.
AB  - BACKGROUND: Zinc supplementation may be beneficial for health. Assessing
      exchangeable zinc pools may be a useful approach to evaluate zinc status.
      OBJECTIVE: We evaluated the effects of long-term supplementation with 2 moderate
      doses of zinc on the mass of exchangeable zinc pools. DESIGN: Three groups of
      healthy, late-middle-aged men (n = 16 per group) participated in a stable-isotope
      zinc kinetic study after 6 mo of daily supplementation with 0 (placebo), 15, or
      30 mg Zn. At the end of the supplementation period, each subject received an
      intravenous injection of 0.89 mg (70)Zn, and the plasma zinc disappearance curve
      was monitored for the next 10 d. Two approaches were used to determine the
      characteristics of the exchangeable zinc pools: 1) formal 3-compartmental
      modeling and 2) a simplified determination of the total mass of the rapidly
      exchangeable zinc pool (EZP). RESULTS: In the placebo group, the exchangeable
      zinc pool masses for the 3 considered pools were as follows: 2.15, 12.7, and
      100.5 mg Zn. The rapidly exchangeable zinc pool mass in the placebo group was 143
      mg Zn. Zinc supplementation significantly increased the exchangeable zinc pool
      masses regardless of the approach used to determine these pools. In addition,
      these data confirm that exchangeable zinc pool masses correlate positively with
      total zinc intake and negatively with subject age and do not correlate with
      plasma zinc concentrations. CONCLUSION: Our data show that long-term
      supplementation with 2 moderate doses of zinc is an efficient way to increase
      exchangeable zinc pool masses in late-middle-aged men.

PMID- 16002808
TI  - Choline supplemented as phosphatidylcholine decreases fasting and postmethionine
      loading plasma homocysteine concentrations in healthy men.
AB  - BACKGROUND: A high homocysteine concentration is a potential risk factor for
      cardiovascular disease that can be reduced through betaine supplementation.
      Choline is the precursor for betaine, but the effects of choline supplementation
      on plasma total homocysteine (tHcy) concentrations in healthy humans are unknown.
      OBJECTIVE: The objective was to investigate whether supplementation with
      phosphatidylcholine, the form in which choline occurs in foods, reduces fasting
      and postmethionine-loading concentrations of plasma tHcy in healthy men with
      mildly elevated plasma tHcy concentrations. DESIGN: In a crossover study, 26 men
      ingested approximately 2.6 g choline/d (as phosphatidylcholine) or a placebo oil
      mixture for 2 wk in random order. Fatty acid composition and fat content were
      similar for both treatments. A methionine-loading test was performed on the first
      and last days of each supplementation period. RESULTS: Phosphatidylcholine
      supplementation for 2 wk decreased mean fasting plasma tHcy by 18% (-3.0
      micromol/L; 95% CI: -3.9, -2.1 micromol/L). On the first day of supplementation,
      a single dose of phosphatidylcholine containing 1.5 g choline reduced the
      postmethionine-loading increase in tHcy by 15% (-4.8 micromol/L; 95% CI: -6.8, 
      2.8 micromol/L). Phosphatidylcholine supplementation for 2 wk reduced the
      postmethionine-loading increase in tHcy by 29% (-9.2 micromol/L; 95% CI: -11.3, 
      7.2 micromol/L). All changes were relative to placebo. CONCLUSIONS: A high daily
      dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as
      postmethionine-loading plasma tHcy concentrations in healthy men with mildly
      elevated tHcy concentrations. If high homocysteine concentrations indeed cause
      cardiovascular disease, choline intake may reduce cardiovascular disease risk in
      humans.

PMID- 16002809
TI  - Zinc absorption and kinetics during pregnancy and lactation in Brazilian women.
AB  - BACKGROUND: Adjustments in zinc absorption and endogenous excretion maintain zinc
      homeostasis in nonpregnant adults fed low-zinc diets. The effects on zinc
      homeostasis of a low zinc intake during pregnancy and lactation have not been
      described in a longitudinal study. OBJECTIVE: We examined longitudinal changes in
      fractional zinc absorption (FZA) and zinc kinetics in 10 healthy Brazilian women
      who habitually consumed a marginal zinc diet ( approximately 9 mg Zn/d). DESIGN:
      Zinc status was measured at 10-12 (early pregnancy; EP) and 34-36 (late
      pregnancy; LP) wk of pregnancy and at 7-8 wk after delivery (early lactation;
      EL). Zinc kinetics and FZA were studied by using stable isotopic tracers.
      RESULTS: Zinc intake averaged 9 +/- 3 mg/d throughout the study. FZA increased
      from 29 +/- 6% at EP to 43 +/- 10% at LP and to 39 +/- 13% at EL (P < 0.05). FZA
      was inversely related to plasma zinc at EL (r = -0.73, P = 0.02) and LP (r = 
      0.72, P = 0.07). Plasma zinc mass was 23% greater at LP than at EP or EL (P <
      0.05). The amount of zinc (mg/d) that fluxed between plasma and the most-rapidly
      turning-over extravascular pool was 53% greater at LP than at EP or EL (P <
      0.05). The zinc flux between plasma and the less-rapidly-turning-over zinc pool
      at EL was 27% greater than that at EP or LP, but this difference was not
      significant. CONCLUSIONS: FZA increased significantly in women with marginal zinc
      intakes during pregnancy and lactation; the increase was higher in women with low
      plasma zinc. Plasma zinc was distributed into a different exchangeable pool at LP
      than at EL.

PMID- 16002810
TI  - Effects of maternal docosahexaenoic acid intake on visual function and
      neurodevelopment in breastfed term infants.
AB  - BACKGROUND: Normal brain and visual development is thought to require exogenous
      docosahexaenoic acid (DHA; 22:6n-3) intake, but the amount needed is debatable.
      Because the supplementation of breastfeeding mothers with DHA increases the DHA
      content of their infants' plasma lipids, we hypothesized that it might also
      improve brain or visual function in the infants. OBJECTIVE: The objective was to
      determine the effect of DHA supplementation of breastfeeding mothers on
      neurodevelopmental status and visual function in the recipient infant. DESIGN:
      Breastfeeding women received capsules containing either a high-DHA algal oil (
      approximately 200 mg DHA/d) or a vegetable oil (no DHA) for 4 mo after delivery.
      Outcome variables included the fatty acid pattern of maternal plasma phospholipid
      and milk lipids 4 mo postpartum, the fatty acid pattern of plasma phospholipids
      and visual function in infants at 4 and 8 mo of age, and neurodevelopmental
      indexes of the infants at 12 and 30 mo of age. RESULTS: Milk lipid and infant
      plasma phospholipid DHA contents of the supplemented and control groups were
      approximately 75% and approximately 35% higher, respectively, at 4 mo postpartum.
      However, neither the neurodevelopmental indexes of the infants at 12 mo of age
      nor the visual function at 4 or 8 mo of age differed significantly between
      groups. In contrast, the Bayley Psychomotor Development Index, but not the Mental
      Development Index, of the supplemented group was higher (P < 0.01) at 30 mo of
      age. CONCLUSION: DHA supplementation of breastfeeding mothers results in higher
      infant plasma phospholipid DHA contents during supplementation and a higher
      Bayley Psychomotor Development Index at 30 mo of age but results in no other
      advantages either at or before this age.

PMID- 16002811
TI  - Biochemical indexes of the B vitamins in cord serum are predicted by maternal B
      vitamin status.
AB  - BACKGROUND: The concentration of total homocysteine (tHcy) is higher in newborns
      than in older children. Vitamin B-12 is the major determinant of tHcy in
      newborns. Maternal status of folate, vitamin B-12, and vitamin B-6 during
      pregnancy may affect the biochemical markers of these micronutrients in newborns.
      OBJECTIVE: Our objective was to study the relation between concentrations of the
      metabolites and B vitamins in maternal sera and concentrations in the umbilical
      venous blood of the corresponding newborns. DESIGN: We studied healthy pregnant
      women at the time of labor who were expecting healthy, full-term, appropriate
      birth-weight babies. Samples were available from 82 mother-infant pairs. RESULTS:
      Concentrations of B vitamins were higher in cord samples than in maternal blood
      (folate, 2-fold; vitamin B-12, 1.5-fold; and vitamin B-6, 6-fold). Concentrations
      of cystathionine and methylmalonic acid (MMA) were also higher in the infants
      than in the mothers (x +/- SD: cystathionine, 462 +/- 189 and 343 +/- 143 nmol/L;
      MMA, 353 +/- 144 and 233 +/- 110 nmol/L). No significant differences in tHcy
      concentrations were observed between fetal and maternal samples. Concentrations
      of vitamin B-12 did not differ significantly between mothers of infants from
      different quartiles of cord MMA. Higher fetal MMA concentrations were related to
      higher maternal MMA and vitamin B-12 concentrations and lower fetal
      concentrations of vitamin B-12. Fetal concentrations of cystathionine were
      predicted by maternal cystathionine, gestational age, fetal vitamin B-6, and
      fetal tHcy. CONCLUSIONS: Maternal concentrations of the metabolic markers of B
      vitamins predict values in fetal blood at delivery. Fetal tHcy concentrations
      were low but were predicted by the vitamin status of the mother. The effect of
      increasing maternal intake of vitamins B-12 and B-6 during pregnancy on the fetal
      concentrations of the metabolites should be investigated.

PMID- 16002812
TI  - A follow-up study of nutrient intake, nutritional status, and growth in infants
      with cow milk allergy fed either a soy formula or an extensively hydrolyzed whey
      formula.
AB  - BACKGROUND: Infants with cow milk allergy (CMA) are reported to have reduced
      growth and special nutritional needs. OBJECTIVE: The aim of the present study was
      to compare nutrient intake, nutritional status, and growth in infants with CMA
      who were fed either a soy formula or an extensively hydrolyzed whey formula.
      DESIGN: The study group comprised 168 double-blind challenge-proven infants with
      CMA. Eighty-four of the infants were fed a soy formula (mean starting age: 7.8
      mo), and the other 84 infants were fed an extensively hydrolyzed whey formula
      (mean starting age: 7.5 mo). RESULTS: The length (SD score) of the infants was
      close to the mean Finnish reference growth by age 2 y in both groups. Weight-for
      length measurements continued to reach the 50th percentile by age 4 y in both
      study groups. The mean nutrient intake followed the recommended intake in both
      groups, although most of the infants were supplemented with calcium and vitamin
      D. The observed serum transferrin receptor concentrations indicated a greater
      iron inadequacy in the tissue of infants in the soy formula group than in the
      hydrolyzed whey formula group (P = 0.08). However, there were no significant
      differences between the groups either in the percentages of abnormally low
      laboratory values (mean cell volume, hemoglobin, zinc, and ferritin) or in the
      percentages of high alkaline phosphatase activity, which indicates the comparable
      safety and effectiveness of the formulas studied. CONCLUSIONS: Both nutritional
      status and growth were well within reference values in the 2 groups, and the
      selection of a formula can largely be made on the basis of infant tolerance to
      the formulas.

PMID- 16002813
TI  - Postprandial response to a physiologic caloric load in HIV-positive patients
      receiving protease inhibitor-based or nonnucleoside reverse transcriptase
      inhibitor-based antiretroviral therapy.
AB  - BACKGROUND: Features of the dyslipidemic pattern reported with the use of
      antiretroviral therapy predict enhanced postprandial lipemia, which is an
      emerging cardiovascular disease risk factor. OBJECTIVE: We evaluated the
      postprandial response to a physiologic, meal-based challenge in HIV-positive
      subjects without hyperlipidemia. DESIGN: We measured hourly lipid, lipoprotein,
      glucose, and insulin concentrations during a 13-h period in 25 nonwhite patients
      (13 women, 12 men): 13 receiving a protease inhibitor (PI)-based regimen (6
      nelfinavir and 7 indinavir) and 12 receiving a nonnucleoside reverse
      transcriptase inhibitor (NNRTI)-based regimen (6 efavirenz and 6 nevirapine).
      RESULTS: Mean fasting HDL-cholesterol concentrations were lower in HIV patients
      than in healthy subjects without HIV infection matched for age, sex, and
      ethnicity (z score: -0.81 +/- 0.9; P = 0.0001). Fasting triacylglycerol
      concentrations were not significantly different between HIV-infected patients and
      healthy subjects but were higher in PI-treated than in NNRTI-treated patients
      [median (interquartile range): 144 (110-191) and 89 (62-135) mg/dL; P = 0.007].
      Average daylong triacylglycerol concentrations, but not incremental
      concentrations, were higher in the PI group than in the NNRTI group [205% (185
      248%) and 125% (78-191%); P < 0.05]. For all HIV-positive patients, the
      fractional triacylglycerol increase was lower after breakfast than after lunch
      (20 +/- 18% and 42 +/- 40%, respectively; P < 0.04). Insulin concentrations were
      higher in PI-treated than in NNRTI-treated patients [22.6 (13.1-29.8) and 11.8
      (7.1-19.1) microU/mL; P = 0.01] and increased in both groups in response to each
      meal, whereas glucose concentrations increased only after breakfast. CONCLUSIONS:
      Despite baseline differences, incremental triacylglycerol and insulin responses
      to a physiologic caloric load among HIV-positive patients were not significantly
      affected by differences in the type of antiretroviral therapy.

PMID- 16002814
TI  - Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the
      relation of folate intake to plasma homocysteine.
AB  - BACKGROUND: Folate intake increases plasma folate and reduces total homocysteine
      (tHcy) concentrations, which may lower coronary artery disease (CAD) and cancer
      risks. Folate metabolism may be altered by alcohol intake and 2 common
      polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, 677C-->T
      and 1298A-->C. OBJECTIVE: We examined whether the associations between folate
      intake and plasma folate and tHcy concentrations were modified by alcohol intake
      or variations in the MTHFR gene. DESIGN: We conducted a cross-sectional analysis
      among 988 women by using multivariate linear regression models to estimate mean
      plasma tHcy and folate concentrations. Folate intake was the sum of food and
      supplemental sources. RESULTS: We observed an inverse association between folate
      intake and tHcy, which was modified by alcohol intake (P for interaction = 0.04)
      and MTHFR677 genotype (P for interaction = 0.05) but not by MTHFR1298 genotype (P
      for interaction = 0.97). In the lowest quintile of folate intake, moderate
      drinkers (>/=15 g alcohol/d) had significantly higher tHcy concentrations (15.2
      +/- 2.9 nmol/mL) than did light drinkers (11.3 +/- 0.7 nmol/mL) and nondrinkers
      (11.0 +/- 0.8 nmol/mL). However, the reduction in tHcy between the highest and
      lowest quintiles of folate intake was significantly greater in moderate drinkers
      (-6.6 nmol/mL) than in light drinkers (-2.3 nmol/mL) and nondrinkers (-2.1
      nmol/mL). The elevated tHcy in women with low folate intake who also consumed
      moderate amounts of alcohol was even higher (22.4 +/- 4.8 nmol/mL) in the
      presence of the variant MTHFR677 allele. The positive association between folate
      intake and plasma folate was somewhat modified by alcohol intake (P for
      interaction = 0.08) but not by either MTHFR genotype. CONCLUSIONS: Moderate
      alcohol intake and low MTHFR activity have adverse effects on tHcy, but those
      effects may be overcome by sufficient folate intake.

PMID- 16002815
TI  - Diet-quality scores and plasma concentrations of markers of inflammation and
      endothelial dysfunction.
AB  - BACKGROUND: Endothelial dysfunction is one of the mechanisms linked to an
      increased risk of cardiovascular disease. OBJECTIVE: We assessed the association
      between several diet-quality scores and plasma concentrations of markers of
      inflammation and endothelial dysfunction. DESIGN: Diet-quality scores on the
      Healthy Eating Index (HEI), Alternate Healthy Eating Index (AHEI), Diet Quality
      Index Revised (DQI-R), Recommended Food Score (RFS), and the alternate
      Mediterranean Diet Index (aMED) were calculated by using a food-frequency
      questionnaire that was administered in 1990 to 690 women in the Nurses' Health
      Study (ages 43-69 y, no cardiovascular disease or diabetes). Blood collection was
      completed in the same year. We used regression analysis to assess the
      associations between these diet-quality scores and plasma concentrations of C
      reactive protein, interleukin 6, E-selectin, soluble intercellular cell adhesion
      molecule 1, and soluble vascular cell adhesion molecule 1. RESULTS: The various
      diet-quality scores were significantly correlated with each other; correlation
      coefficients ranged from 0.56 to 0.80 (all P values < 0.0001). After adjustment
      for age, body mass index, alcohol intake, physical activity, smoking status, and
      energy intake, the HEI and DQI-R were not significantly associated with any of
      the biomarkers, whereas the AHEI and aMED scores were associated with
      significantly lower concentrations of most biomarkers. The RFS was significantly
      associated with a lower concentration of E-selectin only. C-reactive protein
      concentrations were 30% (P < 0.05) and 24% (P < 0.05) lower in the top than in
      the bottom quintile of the AHEI and of the aMED, respectively CONCLUSION: Higher
      AHEI and aMED scores were associated with lower concentrations of biomarkers of
      inflammation and endothelial dysfunction and therefore may be useful as
      guidelines for reducing the risk of diseases involving such biological pathways.

PMID- 16002816
TI  - Compliance with expert population-based dietary guidelines and lower odds of
      carotid atherosclerosis in women: the Framingham Nutrition Studies.
AB  - BACKGROUND: Carotid stenosis, an indicator of subclinical atherosclerosis,
      predicts future coronary artery disease (CAD) and stroke and provides a
      noninvasive method to identify candidates for primary prevention. The relation
      between diet and stenosis is relatively unexplored, particularly in women.
      OBJECTIVE: We evaluated in women the association between nutrient intakes that
      were consistent with expert population-based dietary guidelines and carotid
      stenosis. DESIGN: We used prospective logistic regression analyses to evaluate
      relations between baseline nutrient intake and the presence of carotid stenosis
      at 4-y follow-up in 1123 women from the Framingham Offspring-Spouse study, after
      control for multiple CAD risk factors. We also developed multivariate models that
      were stratified by compliance with expert population-based dietary guidelines and
      smoking status. RESULTS: Baseline nutrient and risk factor profiles differed by
      women's compliance and smoking status. Dietary noncompliance and smoking were
      each associated with odds for stenosis that were 2.5-fold those of dietary
      compliance and nonsmoking. Odds were highest for dietary noncompliance in
      combination with smoking (odds ratio: 3.49; 95% CI: 1.67, 7.27). CONCLUSIONS:
      Nutrient intake consistent with current expert population-based dietary
      guidelines and smoking abstinence are associated with lower odds of carotid
      atherosclerosis in women. Unique dietary and risk factor profiles of at-risk
      women suggest areas for targeted primary CAD prevention.

PMID- 16002817
TI  - Concordant lipoprotein and weight responses to dietary fat change in identical
      twins with divergent exercise levels 1.
AB  - BACKGROUND: Individuals vary greatly in their lipoprotein responses to low-fat
      diets, with some of this variation being attributable to genes. OBJECTIVE: The
      purpose was to test the extent to which individual lipoprotein responses to diet
      can be attributed to genes in the presence of divergent exercise levels. DESIGN:
      Twenty-eight pairs of male monozygotic twins (one twin mostly sedentary, the
      other running an average of 50 km/wk more than the sedentary twin) went from a 6
      wk 40%-fat diet to a 6-wk 20%-fat diet in a crossover design. The diets reduced
      fat primarily by reducing saturated and polyunsaturated fat (both from 14% to 4%)
      while increasing carbohydrate intake from 45% to 65%. RESULTS: Despite the twins'
      differences in physical activity, the dietary manipulation produced significantly
      correlated changes (P < 0.05) in the twins' total cholesterol (r = 0.56); LDL
      cholesterol (r = 0.70); large, buoyant LDL [Svedberg flotation rate (S(f)) 7-12;
      r = 0.52]; apolipoprotein A-I (r = 0.49); lipoprotein(a) (r = 0.49);
      electrophoresis measurements of LDL-I (LDLs between 26 and 28.5 nm in diameter; r
      = 0.48), LDL-IIB (25.2-24.6 nm; r = 0.54), and LDL-IV (22-24.1 nm; r = 0.50); and
      body weight (r = 0.41). Replacing fats with carbohydrates significantly decreased
      the size and ultracentrifuge flotation rate of the major LDL and the LDL mass
      concentrations of large, buoyant LDL; LDL-I; HDL cholesterol; and apolipoprotein
      A-I and significantly increased concentrations of LDL-IIIA (24.7-25.5 nm) and
      lipoprotein(a). CONCLUSIONS: Even in the presence of extreme differences in
      exercise, genes significantly affect changes in LDL, apolipoprotein A-I,
      lipoprotein(a), and body weight when dietary fats are replaced with
      carbohydrates.

PMID- 16002818
TI  - Maternal methylenetetrahydrofolate reductase deficiency and low dietary folate
      lead to adverse reproductive outcomes and congenital heart defects in mice.
AB  - BACKGROUND: Genetic or nutritional disturbances in folate metabolism may affect
      embryonic development because of the critical role of folate in nucleotide
      synthesis and methylation reactions. The possible role of a mild deficiency in
      methylenetetrahydrofolate reductase (MTHFR) and low dietary folate in pregnancy
      outcomes and heart morphogenesis requires further investigation. OBJECTIVE: We
      investigated the effect of mild MTHFR deficiency, low dietary folate, or both on
      resorption rates, on length and weight, and on the incidence of heart
      malformations in murine embryos. DESIGN: Female Mthfr +/+ and +/- mice were fed a
      control diet (CD) or a folic acid-deficient diet (FADD) before mating with male
      Mthfr +/- mice. On gestational day 14.5, implantation and resorption sites were
      recorded and viable embryos were examined for gross malformations, growth delay,
      and congenital heart defects. RESULTS: Plasma homocysteine in Mthfr +/- dams and
      in FADD-treated dams was significantly higher than that in Mthfr +/+ dams and CD
      treated dams, respectively. A significantly higher rate of resorption and greater
      developmental delay were observed in hyperhomocysteinemic mice than in CD-treated
      +/+ dams. Heart defects were identified in 4 of 11, 5 of 10, and 4 of 10 litters
      from CD-treated +/-, FADD-treated +/+, and FADD-treated +/- dams, respectively,
      but not in any of those from CD-treated +/+ dams (0/11 litters). CONCLUSION: Our
      findings suggest that mild MTHFR deficiency, low dietary folate, or both in the
      dams increase the incidence of fetal loss, intrauterine growth retardation, and
      heart defects. These data support the benefit of folic acid supplementation in
      pregnant women, particularly in those with MTHFR deficiency.

PMID- 16002819
TI  - The Ala54Thr polymorphism of the fatty acid-binding protein 2 gene is associated
      with a change in insulin sensitivity after a change in the type of dietary fat.
AB  - BACKGROUND: Insulin resistance, a condition associated with type 2 diabetes,
      results from the interaction of environmental and genetic factors. OBJECTIVE: We
      examined the influence of the intestinal fatty acid-binding protein 2 (FABP2)
      Ala54Thr polymorphism on insulin sensitivity. DESIGN: Fifty-nine healthy young
      subjects (28 were Ala54/Ala54, 27 were Ala54/Thr54, and 4 were Thr54/Thr54)
      completed 3 diets, each of which lasted 4 wk. The first diet, which all subjects
      consumed, was a high-saturated fatty acid (SFA) diet (38% of energy as fat and
      20% of energy as SFAs). The second and third diets were administered according to
      a randomized crossover design, and they consisted of a low-fat and high
      carbohydrate diet (CHO diet; 28% of energy from fat and <10% of energy from SFAs)
      and a high-monounsaturated fatty acid (MUFA) diet (called the Mediterranean diet;
      38% of energy from fat and 22% of energy from MUFAs). All food and drinks were
      prepared and provided in the research kitchen. We determined in vivo insulin
      resistance by using the insulin suppression test with somatostatin. RESULTS:
      Steady state plasma glucose concentrations were significantly higher in Ala54Thr
      subjects after the SFA diet than after the CHO diet or the Mediterranean diet.
      The plasma free fatty acid concentrations in these subjects were significantly
      lower after the CHO and Mediterranean diets than after the SFA diet. However, no
      significant differences between the 3 diets were observed in the Ala54 allele
      homozygotes. CONCLUSION: Insulin sensitivity decreased in subjects with the Thr54
      allele of the FABP2 polymorphism when SFAs were replaced by MUFAs and
      carbohydrates.

PMID- 16002820
TI  - Are the psychological tests valid?

PMID- 16002821
TI  - Science-based solutions to obesity: what are the roles of academia, government,
      industry, and health care?
AB  - The complexity of the obesity epidemic requires the cooperation of key
      stakeholders in this effort. No one sector, academia, government, industry, or
      health care, has been successful in combating this disease to date. On March 10
      11, 2004, The Harvard Medical School Division of Nutrition hosted the symposium
      "Science-Based Solutions to Obesity: What is the Role of Academia, Government,
      Industry, and Health care?" as a platform to address the role of these
      stakeholders, both individually and collectively, in combating the nation's
      epidemic of obesity. The proceedings from the symposium, included in this
      supplement, discuss the following: the science of obesity-related topics such as
      genetics, protein and weight loss, portion size, energy density, and behavior;
      the need for more aggressive government policies; industry's role in using
      research and development capabilities to promote healthier, portion-controlled
      products; and how to translate nutrition information from medical doctors to
      patients.

PMID- 16002822
TI  - Executive summary of the Strategic Plan for National Institutes of Health Obesity
      Research.
AB  - The Strategic Plan for National Institutes of Health (NIH) Obesity Research is
      intended to serve as a guide for coordinating obesity research activities across
      the NIH and for enhancing the development of new efforts based on identification
      of areas of greatest scientific opportunity and challenge. Developed by the NIH
      Obesity Research Task Force with critical input from external scientists and the
      public, the Strategic Plan reflects a dynamic planning process and presents a
      multidimensional research agenda, with an interrelated set of goals and
      strategies for achieving the goals. The major scientific themes around which the
      Strategic Plan is framed include the following: preventing and treating obesity
      through lifestyle modification; preventing and treating obesity through
      pharmacologic, surgical, or other medical approaches; breaking the link between
      obesity and its associated health conditions; and cross-cutting topics, including
      health disparities, technology, fostering of interdisciplinary research teams,
      investigator training, translational research, and education/outreach efforts.
      Through the efforts described in the Strategic Plan for NIH Obesity Research, the
      NIH will strive to facilitate and accelerate progress in obesity research to
      improve public health.

PMID- 16002823
TI  - Genetics of common forms of obesity: a brief overview.
AB  - The obesity epidemic is attributable to dietary and behavioral trends acting on a
      person's genetic makeup to determine body mass and susceptibility to obesity
      related disease. Common forms of obesity have a strong hereditary component, yet
      genetic pathways that contribute to obesity have not yet been elucidated. Many
      genetic association studies have been reported, but few have been successfully
      replicated. New research tools and large studies will lead to an understanding of
      genes and their interaction to cause obesity, which may help guide successful
      interventions and treatments.

PMID- 16002824
TI  - Teaching, learning, doing: best practices in education.
AB  - As many as 90 million Americans lack basic skills needed to access, understand,
      and use health information and services to make healthy dietary choices.
      Effective teaching by physicians can bridge the learning gap and arrest the
      epidemic of obesity. The Academy at Harvard Medical School is developing best
      practices in teaching that will equip future doctors to reduce health illiteracy
      and promote positive changes in thinking and behavior in their patients. Models
      of how people learn can help physicians select tasks, questions, and prompts that
      advance teaching and learning. To keep and use new information, adults need to
      integrate new ideas into existing frameworks of understanding and participate in
      the learning process by linking new information to what is already known. By
      teaching patients how to read a single food label, starting with calories,
      physicians can set the stage for future learning. The process of change is
      challenging, particularly in adults. Best practices in teaching and learning can
      help physicians be more effective agents of change.

PMID- 16002825
TI  - Long-term weight loss maintenance.
AB  - There is a general perception that almost no one succeeds in long-term
      maintenance of weight loss. However, research has shown that approximately 20% of
      overweight individuals are successful at long-term weight loss when defined as
      losing at least 10% of initial body weight and maintaining the loss for at least
      1 y. The National Weight Control Registry provides information about the
      strategies used by successful weight loss maintainers to achieve and maintain
      long-term weight loss. National Weight Control Registry members have lost an
      average of 33 kg and maintained the loss for more than 5 y. To maintain their
      weight loss, members report engaging in high levels of physical activity (
      approximately 1 h/d), eating a low-calorie, low-fat diet, eating breakfast
      regularly, self-monitoring weight, and maintaining a consistent eating pattern
      across weekdays and weekends. Moreover, weight loss maintenance may get easier
      over time; after individuals have successfully maintained their weight loss for 2
      5 y, the chance of longer-term success greatly increases. Continued adherence to
      diet and exercise strategies, low levels of depression and disinhibition, and
      medical triggers for weight loss are also associated with long-term success.
      National Weight Control Registry members provide evidence that long-term weight
      loss maintenance is possible and help identify the specific approaches associated
      with long-term success.

PMID- 16002826
TI  - Physical activity considerations for the treatment and prevention of obesity.
AB  - Overweight and obesity present significant public health concerns because of the
      link with numerous chronic health conditions. Excess body weight is a result of
      an imbalance between energy intake and energy expenditure. Physical activity is
      the most variable component of energy expenditure and therefore has been the
      target of behavioral interventions to modify body weight. It appears that
      physical activity is an important component on long-term weight control, and
      therefore adequate levels of activity should be prescribed to combat the obesity
      epidemic. Although there is evidence that 30 min of moderate-intensity physical
      activity may improve health outcomes, the amount of physical activity that may be
      necessary to control body weight may be >30 min/d. There is a growing body of
      scientific literature suggesting that at least 60 min of moderate-intensity
      physical activity may be necessary to maximize weight loss and prevent
      significant weight regain. Moreover, adequate levels of physical activity appear
      to be important for the prevention of weight gain and the development of obesity.
      Physical activity also appears to have an independent effect on health-related
      outcomes when compared with body weight, suggesting that adequate levels of
      activity may counteract the negative influence of body weight on health outcomes.
      Thus, it is important to target intervention strategies to facilitate the
      adoption and maintenance of an adequate amount of physical activity to control
      body weight.

PMID- 16002827
TI  - Behavioral treatment of obesity.
AB  - Behavioral treatment is an approach used to help individuals develop a set of
      skills to achieve a healthier weight. It is more than helping people to decide
      what to change; it is helping them identify how to change. The behavior change
      process is facilitated through the use of self-monitoring, goal setting, and
      problem solving. Studies suggest that behavioral treatment produces weight loss
      of 8-10% during the first 6 mo of treatment. Structured approaches such as meal
      replacements and food provision have been shown to increase the magnitude of
      weight loss. Most research on behavioral treatment has been conducted in
      university-based clinic programs. Although such studies are important, they tell
      us little about the effectiveness of these approaches in settings outside of
      specialized clinics. Future research might focus more on determining how these
      behavioral techniques can be best applied in a real-world setting.

PMID- 16002828
TI  - The influence of food portion size and energy density on energy intake:
      implications for weight management.
AB  - The increase in the prevalence of obesity has coincided with an increase in
      portion sizes of foods both inside and outside the home, suggesting that larger
      portions may play a role in the obesity epidemic. Although it will be difficult
      to establish a causal relationship between increasing portion size and obesity,
      data indicate that portion size does influence energy intake. Several well
      controlled, laboratory-based studies have shown that providing older children and
      adults with larger food portions can lead to significant increases in energy
      intake. This effect has been demonstrated for snacks and a variety of single
      meals and shown to persist over a 2-d period. Despite increases in intake,
      individuals presented with large portions generally do not report or respond to
      increased levels of fullness, suggesting that hunger and satiety signals are
      ignored or overridden. One strategy to address the effect of portion size is
      decreasing the energy density (kilojoules per gram; kilocalories per gram) of
      foods. Several studies have demonstrated that eating low-energy-dense foods (such
      as fruits, vegetables, and soups) maintains satiety while reducing energy intake.
      In a clinical trial, advising individuals to eat portions of low-energy-dense
      foods was a more successful weight loss strategy than fat reduction coupled with
      restriction of portion sizes. Eating satisfying portions of low-energy-dense
      foods can help to enhance satiety and control hunger while restricting energy
      intake for weight management.

PMID- 16002829
TI  - Protein, body weight, and cardiovascular health.
AB  - Widespread popularity of high-protein diets has drawn controversy as well as
      scientific interest. By reducing intake of carbohydrates and increasing
      consumption of fats and proteins, such diets are thought to increase satiety,
      facilitate weight loss, and improve cardiovascular risk factors. In recent years,
      many randomized controlled studies have compared the effects of higher-protein
      diets on weight loss and cardiovascular risk factors with those of lower-protein
      diets. The aim of this review was to provide an overview of experimental and
      epidemiologic evidence regarding the role of protein in weight loss and
      cardiovascular risk. Emerging evidence from clinical trials indicates that higher
      protein diets increase short-term weight loss and improve blood lipids, but long
      term data are lacking. Findings from epidemiologic studies show a significant
      relationship between increased protein intake and lower risk of hypertension and
      coronary heart disease. However, different sources of protein appear to have
      different effects on cardiovascular disease. Although optimal amounts and sources
      of protein cannot be determined at this time, evidence suggests a potential
      benefit of partially replace refined carbohydrates with protein sources low in
      saturated fats.

PMID- 16002830
TI  - Solutions in weight control: lessons from gastric surgery.
AB  - Surgical therapy is currently the only proven way to achieve significant long
      term weight loss, improve obesity-related comorbidities, reduce the risk of
      premature death, and improve quality of life in a large proportion of treated
      individuals. Roux-en-Y gastric bypass, the most widely performed procedure in the
      United States, is known to achieve permanent (>14 y of follow-up) and significant
      (>50% of excess body weight) weight loss in >90% of patients who undergo the
      operation. Gastric bypass procedures induce physiologic and neuroendocrine
      changes that appear to affect the weight regulatory centers in the brain.
      Researchers have begun to explore the molecular pathways responsible for these
      outcomes. Identifying the differences between surgical and nonsurgical treatments
      will eventually lead to new therapeutic options.

PMID- 16002831
TI  - Now and again: the food and beverage industry demonstrates its commitment to a
      healthy America.
AB  - There exists a complex relationship between food and health in our society that
      is intrinsically linked to our obesity epidemic. The food and beverage industry
      recognizes that it can influence and modify the eating behavior of Americans. The
      American Council for Fitness and Nutrition was formed in January 2003 as a
      partnership of food and beverage companies, trade associations, and nutrition
      advocates that work together to create long-lasting remedies for the obesity
      epidemic. The American Council for Fitness and Nutrition recognizes that the
      current American lifestyle contributes to an energy imbalance and, therefore,
      supports approaches that aim to correct that imbalance. The American Council for
      Fitness and Nutrition also supports the underrepresented populations that are
      disproportionately affected by obesity, specifically, the African American and
      Hispanic American communities. Cooperation between industry, government, and
      academia will be key in establishing long-term strategies to help consumers make
      healthy lifestyle choices.

PMID- 16002832
TI  - When science met the consumer: the role of industry.
AB  - The Coca-Cola Company is committed to understanding consumers and providing
      solutions to help them live active and healthy lifestyles. The Coca-Cola Company
      has developed a wide range of innovative beverages that can be incorporated into
      a healthy diet. Product offerings include beverages with fewer calories, smaller
      package sizes, and expanded beverage fortification options. In addition, the
      company has policies in place that responsibly address advertising to children
      and guidelines for selling beverages to schools. Nutrition education messages
      continue to be delivered through the Internet and on product packaging while
      physical activity initiatives are promoted in schools and communities. The most
      recent initiative has been the creation of The Beverage Institute for Health &
      Wellness. This institute comprises nutritionists, food scientists, physicians,
      and communicators and has been established with the holistic goal of providing
      people all over the world with a wide range of healthy beverages options. The
      institute supports scientific research and consumer education that focuses on the
      role of beverages in a healthy lifestyle. Current projects of the institute
      include the role of hydration in health and performance, alternative beverage
      sweeteners, capturing the natural goodness of fruits and vegetables for beverage
      use, and appropriate beverage fortification.

PMID- 16002833
TI  - Solutions to obesity: perspectives from the food industry.
AB  - Obesity has become an epidemic and an important public health concern. Because
      the problem is multidimensional, the solution will require an interdisciplinary
      approach involving the cooperation of the food industry with other stakeholders,
      such as the government, academia, and health care providers. The consumer is an
      important player in the solution to obesity because the consumer can make healthy
      lifestyle choices at the individual level. The food industry is committed to
      providing the consumer with healthy food options and reliable nutrition
      information.

PMID- 16002834
TI  - Government perspective: food labeling.
AB  - The Food and Drug Administration acknowledges the severity of the obesity
      epidemic. The Food and Drug Administration recognizes the importance of food
      labeling as a vehicle for dietary messages and, thus, enforces stringent
      guidelines to maintain the integrity of the food label. As food labels await
      another upgrade to make them more effective and easier to understand, the Food
      and Drug Administration considers what information will be most useful for
      consumers to make healthy choices. The causal relationship between food labels
      and subsequent diet choice is not well understood; more research in this area is
      needed. The Commissioner of the Food and Drug Administration has recently
      appointed an Obesity Working Group to develop proposals on pertinent topics of
      obesity, including the role of food labeling as a dietary guide.

PMID- 16002835
TI  - The economics of obesity: dietary energy density and energy cost.
AB  - Highest rates of obesity and diabetes in the United States are found among the
      lower-income groups. The observed links between obesity and socioeconomic
      position may be related to dietary energy density and energy cost. Refined
      grains, added sugars, and added fats are among the lowest-cost sources of dietary
      energy. They are inexpensive, good tasting, and convenient. In contrast, the more
      nutrient-dense lean meats, fish, fresh vegetables, and fruit generally cost more.
      An inverse relationship between energy density of foods (kilojoules per gram) and
      their energy cost (dollars per megajoule) means that the more energy-dense diets
      are associated with lower daily food consumption costs and may be an effective
      way to save money. However, economic decisions affecting food choice may have
      physiologic consequences. Laboratory studies suggest that energy-dense foods and
      energy-dense diets have a lower satiating power and may result in passive
      overeating and therefore weight gain. Epidemiologic analyses suggest that the low
      cost energy-dense diets also tend to be nutrient poor. If the rise in obesity
      rates is related to the growing price disparity between healthy and unhealthy
      foods, then the current strategies for obesity prevention may need to be revised.
      Encouraging low-income families to consume healthier but more costly foods to
      prevent future disease can be construed as an elitist approach to public health.
      Limiting access to inexpensive foods through taxes on frowned upon fats and
      sweets is a regressive measure. The broader problem may lie with growing
      disparities in incomes and wealth, declining value of the minimum wage, food
      imports, tariffs, and trade. Evidence is emerging that obesity in America is a
      largely economic issue.

PMID- 16002836
TI  - Hepatic resection: the last surgical frontier for colorectal cancer.

PMID- 16002837
TI  - Does screening for Barrett's esophagus and adenocarcinoma of the esophagus
      prolong survival?
AB  - Despite the paucity of data supporting its use, screening upper endoscopy for
      patients with chronic gastroesophageal reflux disease symptoms to assess for
      Barrett's esophagus and esophageal adenocarcinoma has become a widely accepted
      practice. We apply the principles of screening to Barrett's esophagus and
      esophageal adenocarcinoma. Critical application of the key criteria of screening
      to this situation demonstrates that several criteria are unfulfilled. Key data
      are not available with which to judge other criteria. The major fault with
      screening for Barrett's esophagus is that the at-risk population is too broadly
      characterized and that too many cancers occur outside of this risk pool. Thus,
      recommendations for screening cannot be endorsed. Efforts may be better directed
      at further research identifying groups at risk for esophageal adenocarcinoma,
      developing more accurate and less-invasive methods of diagnosis, and discovering
      the underlying factors which continue to drive the increased incidence of this
      disease.

PMID- 16002838
TI  - Role of endoscopic ultrasonography in the staging and follow-up of esophageal
      cancer.
AB  - PURPOSE: To evaluate the role of endoscopic ultrasonography (EUS) in the initial
      staging and follow-up of esophageal cancer on the basis of a review of the
      published literature. METHODS: Articles published from 1985 to 2005 were searched
      and reviewed using the following keywords: "esophageal cancer staging,"
      "endoscopic ultrasound," and "endoscopic ultrasonography." RESULTS: For initial
      anatomic staging, EUS results have consistently shown more than 80% accuracy
      compared with surgical pathology for depth of tumor invasion (T). Accuracy
      increased with higher stage, and was >90% for T3 cancer. EUS results have shown
      accuracy in the range of 75% for initial staging of regional lymph nodes (N). EUS
      has been invariably more accurate than computed tomography for T and N staging.
      EUS is limited for staging distant metastases (M), and therefore EUS is usually
      performed after a body imaging modality such as computed tomography or positron
      emission tomography. Pathologic staging can be achieved at EUS using fine-needle
      aspiration (FNA) to obtain cytology from suspect Ns. FNA has had greatest
      efficacy in confirming celiac axis lymph node metastases with more than 90%
      accuracy. EUS is inaccurate for staging after radiation and chemotherapy because
      of inability to distinguish inflammation and fibrosis from residual cancer, but a
      more than 50% decrease in tumor cross-sectional area or diameter has been found
      to correlate with treatment response. CONCLUSION: EUS has a central role in the
      initial anatomic staging of esophageal cancer because of its high accuracy in
      determining the extent of locoregional disease. EUS is inaccurate for staging
      after radiation therapy and chemotherapy, but can be useful in assessing
      treatment response.

PMID- 16002839
TI  - Endoscopic mucosal resection for early cancers of the upper gastrointestinal
      tract.
AB  - The purpose of this literature review is to examine recent advances in technique
      and technology of endoscopic mucosal resection of superficial early cancers of
      the upper gastrointestinal tract. Endoscopic mucosal resection (EMR) of
      superficial early cancers of the upper gastrointestinal tract is standard
      technique in Japan and is increasingly used in Western countries. Newer
      techniques of EMR allow removal of larger lesions en-bloc. These minimally
      invasive techniques, when applied correctly, allow safe and efficacious treatment
      in situations that would otherwise require major surgery. Through the
      establishment of long-term outcomes data, standardization of endoscopic and
      pathologic reporting, and newer EMR technology and techniques, the future
      treatment of early cancers in the upper gastrointestinal tract may be achieved
      primarily through the endoscope.

PMID- 16002840
TI  - Development of cell cycle active drugs for the treatment of gastrointestinal
      cancers: a new approach to cancer therapy.
AB  - The cell cycle represents a series of tightly integrated events that allow the
      cell to grow and proliferate. An essential part of the cell cycle machinery is
      the cyclin-dependent kinases (CDKs). When activated, the CDKs provide a means for
      the cell to move from one phase of the cell cycle to the next (G1 to S or G2 to
      M). The cell cycle serves to protect the cell from genotoxic stress. In the
      setting of DNA damage, the CDKs are inhibited and the cell undergoes cell-cycle
      arrest. This provides the cell the opportunity to repair its own damaged DNA
      before it resumes cell proliferation. If a cell continues to cycle with its
      damaged DNA intact, the apoptotic machinery is triggered and the cell will
      undergo apoptosis. In essence, cell cycle arrest at these critical checkpoints
      represents a survival mechanism, which provides the tumor cell the opportunity to
      escape the effects of lethal DNA damage induced by chemotherapy. Over the past
      several years, a series of new targeted agents has been developed that promote
      apoptosis of DNA damaged tumor cells either during cell cycle arrest or following
      premature cell cycle checkpoint exit, such that tumor cells re-enter the cell
      cycle before DNA repair is complete. An understanding of the cell cycle and its
      relationship to p53 are critical for the successful clinical development of these
      agents for the treatment of patients with gastrointestinal cancers.

PMID- 16002841
TI  - Optimal locoregional treatment in gastric cancer.
AB  - Worldwide, gastric cancer is one of the leading causes of cancer-related death.
      The mainstay of curative treatment is radical surgery. But even with optimal
      surgical resection, the prognosis remains modest in the Western world. Numerous
      attempts have been undertaken to improve clinical outcome. More extensive lymph
      node dissection, adjuvant radiotherapy and adjuvant chemotherapy did not result
      in a survival benefit in randomized trials. Only postoperative chemoradiotherapy
      has proven to be valuable in prospective randomized trials. Questions are to be
      answered about optimization of surgery, radiotherapy and chemotherapy, and fine
      tuning of the three modalities. One of the key issues that should be addressed is
      whether pre- or postoperative chemoradiotherapy will benefit survival or
      locoregional control in the case of optimal surgery with an "over-D1"
      lymphadenectomy and without splenectomy. In this article the most relevant
      literature on locoregional treatment in operable gastric cancer will be reviewed
      and future strategies will be discussed.

PMID- 16002842
TI  - Intraductal papillary mucinous tumors of the pancreas.
AB  - Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are increasingly
      recognized in clinical practice. They are a unique clinicopathologic entity that
      is characterized by mucin production, cystic dilation of the pancreatic ducts,
      and intraductal papillary growth. Histologically, they may demonstrate a spectrum
      of cellular atypia ranging from minimal mucinous hyperplasia to frank invasive
      carcinoma. Similar to invasive ductal adenocarcinoma of the pancreas, patients
      with IPMN generally present in the seventh or eighth decade of life with the head
      of the gland being the predominant disease site. The majority of patients are
      symptomatic at presentation with abdominal pain, weight loss, and diarrhea being
      the predominant symptoms. Traditionally, the diagnosis was made following an
      endoscopic retrograde cholangiopancreatography. However, a cross-sectional
      imaging study such as a computed tomography or magnetic resonance imaging is now
      the radiological imaging studies of choice. Current thinking suggests that at
      best IPMN represents a premalignant condition and, as such, surgical intervention
      should be recommended. The aim should be to resect all gross disease while
      attempting to achieve a negative surgical margin, which in the majority of cases
      can be achieved by a partial pancreatectomy. The disease seems to be somewhat
      indolent with resection of noninvasive disease being curative in the majority of
      patients with 5- and 10-year actuarial survival rates of 75% and 60% reported.
      However, up to 50% of cases will have invasive cancer, and for this cohort the
      prognosis is more guarded. The role of adjuvant therapies is unclear, and further
      studies are required in this area.

PMID- 16002843
TI  - Molecular markers of early pancreatic cancer.
AB  - Pancreatic cancer is a deadly disease and the fourth most common cause of cancer
      death in the United States. Since chemotherapy and radiotherapy have thus far
      largely failed to significantly improve the survival of patients with pancreatic
      ductal adenocarcinoma, there is considerable interest in identifying better
      diagnostic markers of pancreatic neoplasia. Not only could better markers improve
      the early diagnosis of pancreatic cancer and allow more patients to undergo
      curative surgical resection, but also could potentially be used for patients at
      high risk of developing pancreatic cancer to identify precancerous lesions while
      they are amenable to cure. A wealth of information has recently become available
      about gene expression, DNA methylation, and proteomics alterations that occur in
      pancreatic cancers creating hope that better diagnostic markers of pancreatic
      cancer will be soon forthcoming.

PMID- 16002844
TI  - Adjuvant treatment for resectable pancreatic cancer.
AB  - There are relatively few randomized studies of adjuvant chemoradiotherapy and
      chemotherapy in patients with resected pancreatic adenocarcinoma. The European
      Study Group for Pancreatic Cancer 1 (ESPAC1) trial is the largest study of
      adjuvant treatment to date. The results of ESPAC1 are discussed in the context of
      other evidence from previous randomized studies, which have also been combined in
      a meta-analysis. Overall, the existing data show a clear benefit for
      postoperative adjuvant chemotherapy, which has not been demonstrated for adjuvant
      chemoradiotherapy. The subgroup of patients with resection margin positive
      disease did seem to benefit less from adjuvant chemotherapy, and showed a trend
      towards improved survival with chemoradiotherapy. Adjuvant chemoradiotherapy
      should be evaluated further in this latter group of patients. The optimal
      chemotherapy regimen for use as adjuvant treatment is the subject of ongoing
      trials. Other strategies which should be explored include neoadjuvant treatment
      and the incorporation of novel targeted agents into management.

PMID- 16002845
TI  - Locally advanced pancreatic cancer.
AB  - Of the 32,180 patients diagnosed with pancreatic carcinoma in the United States
      this year, approximately 40% will present with locally advanced disease.
      Radiotherapeutic approaches are often employed because these patients have
      unresectable tumors by virtue of local invasion into the retroperitoneal vessels
      in the absence of clinically detectable metastases. These treatments include
      external-beam irradiation with and without fluorouracil-based chemotherapy,
      intraoperative irradiation, and, more recently, external-beam irradiation with
      new systemic targeted agents.

PMID- 16002846
TI  - Role of genomic markers in colorectal cancer treatment.
AB  - For the last four decades, fluorouracil (FU) has been the main treatment of
      choice in colorectal cancer (CRC) in both the advanced and adjuvant settings. In
      the advanced setting, FU monotherapy produces response rates of only 10% to 20%.
      Furthermore, in resected stage III CRC, FU monotherapy has increased overall
      survival by only 20%. The combination of FU with newer therapies such as
      oxaliplatin and irinotecan has significantly improved response rates to 40% to
      50%. Despite these improvements, more than half of advanced CRC patients derive
      no benefit from treatment; this is due to either acquired or inherent drug
      resistance. This review aims to highlight the current prognostic and predictive
      markers that have been identified for CRC to date. The limited use of these
      predictive markers underscores the importance of and need for multiple marker
      testing in order to improve response rates and decrease toxicity. This review
      will also focus on high throughput methods to identify panels of predictive
      markers for CRC, which ultimately aim to tailor treatment according to an
      individual patient and tumor profile.

PMID- 16002848
TI  - Endoscopic techniques to diagnose and manage biliary tumors.
AB  - Malignancies of the bile duct are often suspected in patients with abnormal serum
      hepatic enzyme levels and obstruction of the biliary system. Although cross
      sectional imaging can provide evidence for biliary obstruction and a malignancy
      arising from the bile duct, a definitive diagnosis is often obtained through the
      use of endoscopic procedures. Endoscopic retrograde cholangiopancreatography
      (ERCP), the most commonly performed procedure for cholangiocarcinoma, can provide
      a tissue diagnosis through brush cytology of the bile duct. Relief from biliary
      obstruction can be provided with temporary plastic stenting or permanent metal
      stenting. Photodynamic therapy guided by ERCP may provide improved palliation
      from biliary obstruction in the future. Endoscopic ultrasonography complements
      the role of ERCP and may provide a tissue diagnosis through fine-needle
      aspiration and staging through ultrasound imaging. High-resolution ultrasound
      images can provide detailed information regarding the relationship between a mass
      and the bile duct wall. Despite these advances in endoscopic techniques and
      imaging of the bile duct, a tissue diagnosis often remains elusive in many
      patients. In the future, molecular markers will be employed to improve the
      sensitivity for the detection of malignancy in bile duct samples obtained through
      brushing, aspiration, and biopsy.

PMID- 16002847
TI  - Systemic therapy for metastatic colorectal cancer: current options, current
      evidence.
AB  - Combination chemotherapy regimens including irinotecan and oxaliplatin markedly
      improve response rate and prolong median survival over fluorouracil with
      leucovorin (FU/LV), and have supplanted FU/LV as the standard systemic approach
      for metastatic colorectal cancer. The recent availability of five active
      chemotherapeutic agents has doubled the median overall survival for metastatic
      colorectal cancer from 10 to 20 months, and though the optimal strategy for
      incorporation of all drugs is still unclear, current data support the use of
      chemotherapy doublets in first-line rather than sequential single-agent therapy.
      Multidrug regimens increase both response rate and the proportion of patients
      able to undergo potentially curative resection. In addition, as many as 20% to
      30% of patients never receive second-line chemotherapy. When used as single
      agents, bolus and infusional FU/LV and capecitabine are similarly effective but
      have differing toxicity. Chemotherapy combinations that incorporate infusion of
      FU are less toxic and more effective than those using bolus FU dosing.
      Capecitabine is under study as an alternative dosing method for use in
      combination regimens; however, the optimal dose has not been defined and final
      safety and efficacy outcomes are being addressed in ongoing phase II and III
      investigations. Three combinations have shown excellent first-line efficacy in
      phase III trials--IFL with bevacizumab, FOLFOX, and FOLFIRI--but neither of these
      combinations is clearly superior. Sound clinical judgment must continue to guide
      treatment decisions while we await data regarding the optimal combination and
      sequence of fluorouracil, irinotecan, oxaliplatin, bevacizumab, and cetuximab.

PMID- 16002849
TI  - Mumps outbreak among young adults in UK.

PMID- 16002850
TI  - Describing the road to death.

PMID- 16002851
TI  - Mediterranean diet health benefits may be due to a synergistic combination of
      phytochemicals and fatty-acids.

PMID- 16002852
TI  - Rational health care should be offered to all persons: rich or poor, well or
      sick.

PMID- 16002853
TI  - Doctor who ran nursing home is cleared of professional misconduct.

PMID- 16002854
TI  - NHS foundation trusts.

PMID- 16002855
TI  - Epilepsy and driving.

PMID- 16002856
TI  - Regulating herbal medicines in the UK.

PMID- 16002857
TI  - The quest for quality in the NHS: still searching?

PMID- 16002858
TI  - Lifestyle contributes most to distribution of cancer, report says.

PMID- 16002859
TI  - Humanising "an intimidating instrument".

PMID- 16002860
TI  - Meadow defends his role in conviction of Sally Clark.

PMID- 16002862
TI  - Doctors campaign for ban on smoking in enclosed public places.

PMID- 16002863
TI  - GPs appear before GMC accused of missing warning signs in deaths of Shipmans
      patients.

PMID- 16002864
TI  - WHO puts abortifacients on its essential drug list.

PMID- 16002868
TI  - Home test shows sex of fetus at five weeks of pregnancy.

PMID- 16002872
TI  - Access to clean water in rural Africa is inadequate.

PMID- 16002873
TI  - Public distrusts government health campaigns, experts say.

PMID- 16002874
TI  - Queensland report on deaths recommends sweeping changes.

PMID- 16002876
TI  - Woman gives birth after receiving transplant of her own ovarian tissue.

PMID- 16002877
TI  - Public health scientists accused of soft peddling the dangers of passive smoking
      after taking grants from tobacco related organisations.

PMID- 16002878
TI  - FDA warns that antidepressants may increase suicidality in adults.

PMID- 16002879
TI  - WHO launches "plan of war" to tackle avian flu.

PMID- 16002880
TI  - Shining a light on suffering.

PMID- 16002881
TI  - Value of routine funduscopy in patients with hypertension: systematic review.
AB  - OBJECTIVE: To evaluate the additional value of funduscopy in the routine
      management of patients with hypertension. DESIGN: Systematic review.
      PARTICIPANTS: Adults aged 19 or more with hypertensive retinopathy. DATA SOURCES:
      Medline, Embase, and the Cochrane Library from 1990. REVIEW METHODS: Studies were
      included that assessed hypertensive retinopathy with blinding for blood pressure
      and cardiovascular risk factors. Studies on observer agreement had to be assessed
      by two or more observers and expressed as a kappa statistic. Studies on the
      association between hypertensive retinopathy and hypertensive organ damage were
      carried out in patients with hypertension. The association between hypertensive
      retinopathy and cardiovascular risk was carried out in unselected normotensive
      and hypertensive people without diabetes mellitus. RESULTS: The assessment of
      microvascular changes in the retina is limited by large variation between
      observers. The positive and negative predictive values for the association
      between hypertensive retinopathy and blood pressure were low (47% to 72% and 32%
      to 67%, respectively). Associations between retinal microvascular changes and
      cardiovascular risk were inconsistent, except for retinopathy and stroke. The
      increased risk of stroke, however, was also present in normotensive people with
      retinopathy. These studies did not adjust for other indicators of hypertensive
      organ damage. CONCLUSION: Evidence is lacking that routine funduscopy is of
      additional value in the management of hypertensive patients.

PMID- 16002882
TI  - Effect of introduction of integrated out of hours care in England: observational
      study.
AB  - OBJECTIVES: To quantify service integration achieved in the national exemplar
      programme for single call access to out of hours care through NHS Direct, and its
      effect on the wider health system. DESIGN: Observational before and after study
      of demand, activity, and trends in the use of other health services.
      PARTICIPANTS: 34 general practice cooperatives with NHS Direct partners
      (exemplars): four were case exemplars; 10 control cooperatives. SETTING: England.
      MAIN OUTCOME MEASURES: Extent of integration; changes in demand, activity, and
      trends in emergency ambulance transports; attendances at emergency departments,
      minor injuries units, and NHS walk-in centres; and emergency admissions to
      hospital in the first year. RESULTS: Of 31 distinct exemplars, 21 (68%)
      integrated all out of hours call management. Nine (29%) achieved single call
      access for all patients. In the only case exemplar where direct comparison was
      possible, a higher proportion of telephone calls were handled by cooperative
      nurses before integration than by NHS Direct afterwards (2622/6687 (39%) v
      2092/7086 (30%): P < 0.0001). Other case exemplars did not achieve 30%. A small
      but significant downturn in overall demand for care seen in two case exemplars
      was also seen in the control cooperatives. The number of emergency ambulance
      transports increased in three of the four case exemplars after integration,
      reaching statistical significance in two (5%, -0.02% to 10%, P = 0.06; 6%, 1% to
      12%, P = 0.02; 7%, 3% to 12%, P = 0.001). This was always accompanied by a
      significant reduction in the number of calls to the integrated service.
      CONCLUSION: Most exemplars achieved integration of call management but not single
      call access for patients. Most patients made at least two telephone calls to
      contact NHS Direct, and then waited for a nurse to call back. Evidence for
      transfer of demand from case exemplars to 999 ambulance services may be amenable
      to change, but NHS Direct may not have sufficient capacity to support national
      implementation of the programme.

PMID- 16002884
TI  - The patient's journey: living with locked-in syndrome.

PMID- 16002885
TI  - Displaced populations and long term humanitarian assistance.

PMID- 16002886
TI  - Five futures for academic medicine: the ICRAM scenarios.

PMID- 16002887
TI  - The future for medical education.

PMID- 16002888
TI  - Universities have a vital role.

PMID- 16002889
TI  - How far is the future?

PMID- 16002890
TI  - Challenging the patience of patients.

PMID- 16002891
TI  - Calcium and vitamin D in preventing fractures: data are not sufficient to show
      inefficacy.

PMID- 16002892
TI  - Calcium and vitamin D in preventing fractures: dietary intake of calcium needs to
      be considered.

PMID- 16002893
TI  - Calcium and vitamin D in preventing fractures: vitamin K supplementation has
      powerful effect.

PMID- 16002894
TI  - Participants in research: routine extrapolation of randomised controlled trials
      is absurd.

PMID- 16002895
TI  - Vitamin D deficiency may have role in chronic low back pain.

PMID- 16002896
TI  - Surveying the literature from animal experiments: avoidance of bias is objective
      of systematic reviews, not meta-analysis.

PMID- 16002897
TI  - Surveying the literature from animal experiments: systematic review and meta
      analysis are important contributions.

PMID- 16002898
TI  - Participants in research: contract to run a trial should include patient
      researchers in steering groups.

PMID- 16002899
TI  - Participants in research: patients in clinical trials are protected by consumer
      regulation.

PMID- 16002901
TI  - Horizon: Does the MMR Jab cause autism?: We cannot win.

PMID- 16002902
TI  - Horizon: Does the MMR jab cause autism? Has the fat lady sung then?

PMID- 16002904
TI  - Cardiac sarcoidosis: there is no instant replay.

PMID- 16002905
TI  - Cause and effect in lung cancer: fueling the fire.

PMID- 16002906
TI  - Pretransplant pulmonary evaluation of the blood and marrow transplant recipient.

PMID- 16002907
TI  - Monotherapy in severe community-acquired pneumonia: is it worthy?

PMID- 16002908
TI  - The "Goldilocks" principle.

PMID- 16002909
TI  - Caveats of bispectral index monitoring in the pediatric population.

PMID- 16002910
TI  - Bronchoscopy for lung cancer.

PMID- 16002911
TI  - B-type natriuretic peptide and echocardiographic determination of ejection
      fraction in the diagnosis of congestive heart failure in patients with acute
      dyspnea.
AB  - BACKGROUND: Echocardiography and B-type natriuretic peptide (BNP) are diagnostic
      tests for congestive heart failure (CHF), but an emergency diagnosis can be
      difficult. OBJECTIVE: To assess the diagnostic performance of BNP testing and
      echocardiographic assessment of left ventricular systolic function, separately
      and combined, for the identification of CHF in patients with acute dyspnea.
      DESIGN: Prospective, multinational, multicenter study. SETTING: Patients
      presenting to emergency departments in seven hospitals between June 1999 and
      December 2000. PATIENTS: A total of 1,586 patients with acute dyspnea. MAIN
      OUTCOME MEASURES: Echocardiographic determination of ejection fraction (EF) and
      point-of care BNP measurement for the diagnosis of CHF. RESULTS: Seven hundred
      nine of the 1,586 patients underwent echocardiography; 492 patients (69.4%) had a
      final diagnosis of CHF. Patients with CHF were older (68.5 years vs 61.6 years, p
      < 0.0001), had a lower EF (39.5% vs 56.1%, p < 0.0001), and a higher BNP (683
      pg/mL vs 129 pg/mL, p < 0.0001) than patients without CHF. Area under the
      receiver operating characteristic (ROC) curve for the diagnosis of CHF was
      significantly higher for BNP (0.89) than for EF (0.78; area under the ROC curve
      difference, 0.12; p < 0.0001). The sensitivity of BNP > or = 100 pg/mL for the
      diagnosis of CHF was 89%, and specificity was 73%. Values for EF < or = 50% had a
      sensitivity of 70% and a specificity of 77%. Multivariate logistic regression
      analysis showed that, in combination with clinical, ECG, and chest radiograph
      data, BNP > or = 100 pg/mL and EF < or = 50% remained independent predictors of
      CHF (odds ratios, 32.1 and 6.2, respectively). The proportions of patients who
      were correctly classified were 67% for BNP alone, 55% for EF alone, 82% for the
      two variables together, and 97.3% when clinical, ECG, and chest radiograph data
      were added. CONCLUSION: BNP measurement was superior to two-dimensional
      echocardiographic determination of EF in identifying CHF, regardless of the
      threshold value. The two methods combined have marked additive diagnostic value.

PMID- 16002912
TI  - Cardiac involvement in patients with pulmonary sarcoidosis assessed at two
      university medical centers in the Netherlands.
AB  - STUDY OBJECTIVES: We aimed to determine cardiac involvement in patients with
      pulmonary sarcoidosis (PS) followed up at two university medical centers in the
      Netherlands. DESIGN: We reviewed the findings in consecutive patients assessed by
      our departments during 1998 to 2004, and classified them as patients who had
      presented with symptoms of cardiac sarcoidosis (CS) [group A], and those who had
      been screened for this condition (group B). SETTING: Two university medical
      centers in the Netherlands. PATIENTS: One hundred one patients (69 men [mean age,
      47.6 years] and 32 women [mean age, 47.3 years]) with biopsy-proven PS.
      INTERVENTIONS: Twelve-lead ECG (n = 101), ambulatory ECG (n = 74),
      echocardiography (n = 80), (201)Tl single-photon emission CT (n = 61), cardiac
      MRI (n = 87), coronary angiography to exclude coronary artery disease (n = 17),
      and endomyocardial biopsy (n = 9). MEASUREMENTS: ECG, structural, and functional
      cardiac abnormalities according to the modified guidelines of the Japanese
      Ministry of Health and Welfare (1993). RESULTS: Sixteen of 19 patients in group A
      and 3 of 82 patients in group B received a diagnosis of CS. During a mean follow
      up of 1.7 years (range, 3 months to 4 years), four patients in group A died (20%)
      and nine patients received a pacemaker and/or an implantable cardioverter
      defibrillator (47%), while the patients in group B had an uncomplicated course.
      CONCLUSIONS: Once symptomatic CS develops in PS patients, the prognosis becomes
      very grim. In contrast, the prognosis in asymptomatic cardiac involvement in PS
      patients is good. Considering the poor prognosis of symptomatic CS,
      pulmonologists should consider regular screening of their PS patients for cardiac
      involvement with straightforward detection methods.

PMID- 16002913
TI  - Percutaneous transluminal mitral valvuloplasty reduces circulating soluble CD40
      ligand in rheumatic mitral stenosis.
AB  - BACKGROUND: Recent data suggest that the pathogenesis of vascular inflammation
      and thrombosis involves CD40 ligand (CD40L), which is mostly derived from
      platelets. Previous studies have demonstrated that platelet activation occurs in
      peripheral blood of patients with rheumatic mitral stenosis (MS). However, in
      patients with MS, the plasma level of soluble CD40L has never been investigated.
      METHODS AND RESULTS: Seventeen patients with symptomatic MS undergoing
      percutaneous transluminal mitral valvuloplasty were studied (group 1, 11 patients
      in permanent atrial fibrillation and 6 patients in sinus rhythm). Solid-phase,
      sandwich enzyme-linked immunosorbent assay determined the plasma levels of
      soluble CD40L in the femoral vein and artery, and right and left atria before
      valvuloplasty, and those in the peripheral venous blood obtained 10 min after
      valvuloplasty, and at the 4-week follow-up after valvuloplasty. The Doppler
      pressure half-time method was used to calculate the mitral valve area.
      Additionally, plasma concentrations of soluble CD40L in the peripheral venous
      blood obtained from 17 control patients were measured (including nine healthy
      volunteers in sinus rhythm [group 2] and eight patients in permanent lone atrial
      fibrillation [group 3]). Plasma levels of soluble CD40L were significantly
      elevated in group 1 patients (437.6 +/- 370.2 pg/mL) [mean +/- SD] compared with
      group 2 (203.8 +/- 218.0 pg/mL) and group 3 patients (173.5 +/- 105.0 pg/mL) [p <
      0.05]. The area of mitral valve increased significantly after valvuloplasty (1.10
      +/- 0.20 cm(2) vs 1.47 +/- 0.29 cm(2), p < 0.0001). The mean left atrial pressure
      fell significantly and immediately after valvuloplasty (22.8 +/- 4.9 mm Hg vs
      17.6 +/- 5.5 mm Hg, p = 0.0004). The peripheral venous plasma levels of soluble
      CD40L obtained before valvuloplasty significantly fell after valvuloplasty
      (before, 437.6 +/- 370.2 pg/mL; vs 10 min after, 215.4 +/- 113.9 pg/mL; vs 4
      weeks after, 217.5 +/- 111.9 pg/mL; p < 0.02). CONCLUSIONS: Patients with
      moderate-to-severe MS had higher venous plasma levels of soluble CD40L than
      healthy volunteers or patients with lone atrial fibrillation. Additionally, the
      elevated venous plasma levels of soluble CD40L fell significantly following
      valvuloplasty.

PMID- 16002914
TI  - Stress recovery index for risk stratification of asymptomatic patients following
      coronary bypass surgery.
AB  - OBJECTIVE: To prospectively assess the prognostic value of the stress recovery
      index (SRI) following coronary bypass surgery. DESIGN AND PATIENTS: Two hundred
      seventy-eight patients who had undergone coronary bypass surgery and participated
      in a secondary prevention program were exercise tested and prospectively followed
      up for a median of 36 months. Cardiac death, nonfatal infarction, and need for
      further revascularization were target end points. SRI, defined as the difference
      in absolute values between the area of heart rate-adjusted ST-segment depression
      during exercise and recovery, was derived in all. Clinical data, resting ejection
      fraction, and exercise testing data of patients were entered into a sequential
      Cox model; SRI was entered last. Model validation was performed by bootstrap
      adjusted by the degree of optimism in estimates. Survival curves were set up
      using Kaplan-Meier method and compared by the log-rank test. RESULTS: SRI was the
      only significant and independent prognostic indicator (hazard ratio, 0.68; 95%
      confidence interval, 0.53 to 0.89) and increased the prognostic power of the
      model on top of clinical and exercise testing variables, as demonstrated by the
      significant (p = 0.01) increase of the area under the receiver operating
      characteristic curve of the risk function. Survival analysis showed ascending SRI
      quartiles to identify a significant (p = 0.001) increase in event-free survival.
      CONCLUSIONS: SRI is of value in predicting outcome after coronary bypass surgery
      and provides additional prognostic information over clinical and exercise testing
      data.

PMID- 16002915
TI  - A randomized controlled trial to assess the optimal dose and effect of nebulized
      albuterol in acute exacerbations of COPD.
AB  - STUDY OBJECTIVES: Despite the widespread use of short-acting, inhaled beta(2)
      agonists in acute exacerbations of COPD (AECOPDs), little is known about their
      optimal dose. The aims of this study are to compare the bronchodilator response
      to incremental doses of inhaled albuterol during and after recovery from an
      AECOPD, and to compare the effects of regular nebulized albuterol, 2.5 mg and 5
      mg, on the speed of recovery. METHODS: Eighty-six patients admitted with an
      AECOPD were recruited. Each patient was administered incremental doses of inhaled
      albuterol on hospital admission and following recovery. Dose-response curves were
      constructed based on FEV(1) and peak expiratory flow rate (PEFR) recorded after
      each incremental dose. Patients were then randomized in a double-blind fashion to
      receive 2.5 mg or 5 mg of nebulized albuterol q4h until recovery. Twice-daily
      PEFR, the number of extra doses of bronchodilators, and side effects reported
      were recorded. RESULTS: Maximal bronchodilation (Emax) FEV(1) (maximal
      bronchodilatory response to albuterol) increased from 0.64 +/- 0.27 L/min during
      the exacerbation to 0.94 +/- 0.38 L/min during recovery (p < 0.001). The Emax
      PEFR increased from 147.53 +/- 62.46 L/min to 222.94 +/- 73.82 L/min after
      recovery (p = < 0.001). There was no significant difference in rate of recovery
      of PEFR (p = 0.684), duration of hospital stay (p = 0.084), or side effects (p =
      0.506) between the groups receiving 2.5 mg or 5 mg of nebulized albuterol.
      CONCLUSIONS: There was significant improvement in Emax to inhaled albuterol as
      the COPD exacerbation resolved. There was no significant difference in outcomes
      including length of hospital stay or recovery of lung function between patients
      treated with regular 2.5 mg vs 5 mg of nebulized albuterol during an AECOPD.

PMID- 16002916
TI  - Encouraged 6-min walking test indicates maximum sustainable exercise in COPD
      patients.
AB  - STUDY OBJECTIVES: In patients with moderate-to-severe COPD, an encouraged 6-min
      walking test (6MWT) is a high-intensity submaximal exercise protocol that shows
      an oxygen uptake (Vo(2)) plateau after the third minute of the test. This last
      feature prompted the hypothesis that self-paced walking speed is set to achieve
      "maximal" sustainable Vo(2), namely "critical power" or "critical speed."
      PATIENTS AND METHODS: Eight patients with moderate-to-severe COPD (mean age, 68
      +/- 7 years [+/- SD]; FEV(1), 50 +/- 13% predicted; Pao(2), 69 +/- 8 mm Hg)
      underwent the following tests on different days in order: (1) encouraged 6MWT;
      (2) standard incremental shuttle test to identify peak walking speed; (3) four
      different high-intensity, constant walking speed tests to exhaustion to calculate
      critical walking speed; and (4) timed walking test at critical walking speed
      (CWS) to examine sustainability of the exercise. RESULTS: 6MWT and CWS showed
      similar results (mean of last 3 min): Vo(2) (1,605 +/- 304 mL/min vs 1,584 +/-
      319 mL/min), minute ventilation (47 +/- 12 L/min vs 48 +/- 11 L/min), respiratory
      exchange ratio (0.89 +/- 0.1 vs 0.90 +/- 0.1), heart rate (130 +/- 18 beats/min
      vs 131 +/- 16 beats/min), Borg dyspnea score (5.4 +/- 1.3 vs 5.5 +/- 2.4), and
      walking speed (1.49 +/- 0.1 m/s vs 1.44 +/- 0.1 m/s, respectively). CONCLUSION:
      This study supports that 6MWT indicates maximum sustainable exercise that might
      be related with its predictive value in COPD patients.

PMID- 16002917
TI  - Exercise capacity deterioration in patients with COPD: longitudinal evaluation
      over 5 years.
AB  - BACKGROUND: Although exercise capacity is an important outcome measure in
      patients with COPD, its longitudinal course has not been analyzed in comparison
      to the change in pulmonary function. PURPOSES: To examine how exercise capacity
      would deteriorate over time in patients with COPD, and what factors would
      contribute to it. METHODS: A total of 137 male outpatients with moderate-to-very
      severe COPD were examined. The average age was 69.0 +/- 6.6 years (+/- SD), and
      the mean postbronchodilator FEV(1) was 45.9 +/- 15.4% predicted. Progressive
      cycle ergometry and pulmonary function testing were performed at entry, and every
      6 months thereafter over 5 years. Due to the presence of missing data, a mixed
      effect model analysis was then used to estimate the longitudinal changes in
      various clinical parameters. RESULTS: Peak oxygen uptake (Vo(2)), peak minute
      ventilation (Ve), and peak tidal volume (Vt) during exercise declined
      significantly over time (p < 0.0001), which was no less rapid than the
      deterioration in FEV(1). The mean decline rates for peak Vo(2) were 32 +/- 60
      mL/min/yr and 0.5 +/- 1.0 mL/min/kg/yr. Multiple regression analysis revealed
      that the changes in peak Ve, peak Vt, and peak respiratory rates were significant
      predictors for the change in peak Vo(2). CONCLUSION: We demonstrated clear
      evidence of measurable and progressive deterioration in exercise capacity in COPD
      patients, which was no less rapid than the decline in airflow limitation. Dynamic
      ventilatory constraints during exercise also deteriorated over time, which most
      significantly contributed to this exercise capacity deterioration. In addition to
      pulmonary function, the longitudinal follow-up of exercise capacity is important
      not to miss the overall deterioration in COPD.

PMID- 16002918
TI  - Effects of mometasone furoate dry powder inhaler and beclomethasone dipropionate
      hydrofluoroalkane and chlorofluorocarbon on the hypothalamic-pituitary-adrenal
      axis in asthmatic subjects.
AB  - STUDY OBJECTIVES: Mometasone furoate dry powder inhaler (MF-DPI) [400 mug] is an
      inhaled corticosteroid (ICS) that is effective in the treatment of asthma. MF-DPI
      has a low potential for suppression of the hypothalamic-pituitary-adrenal (HPA)
      axis at its clinical dose. The effect of MF-DPI, 400 microg qd, on the HPA axis
      was compared to that of beclomethasone dipropionate (BDP) using hydrofluoroalkane
      (HFA) and chlorofluorocarbon (CFC) propellants via metered-dose inhalers (MDIs)
      twice daily. DESIGN AND INTERVENTIONS: This randomized, third-party blind,
      parallel-group study compared the effects of MF-DPI 400 mug one puff qd in the
      morning (n = 18), HFA-BDP 200 microg two puffs MDI bid (n = 18), and CFC-BDP 400
      microg two puffs MDI bid (n = 17) for 14 days on the area under the 24-h serum
      cortisol concentrations curve (AUC(0-24)) and on total 24-h urinary free cortisol
      excretion in mild asthmatic subjects. Effects on morning/evening peak expiratory
      flow (PEF) and on inhaled albuterol use were also assessed. Adverse events that
      occurred during or > or = 30 days after the study were recorded. RESULTS: The
      mean decrease from baseline in the serum cortisol concentrations AUC(0-24) in the
      MF-DPI group was significantly less than in either the HFA-BDP (p = 0.024) or the
      CFC-BDP (p = 0.011) groups. Decreases in serum cortisol concentrations AUC(0-24)
      in the two BDP groups did not differ from one another. The MF-DPI group trended
      toward higher morning and evening PEF than either BDP group. Treatment-associated
      adverse events were reported by seven subjects in the MF-DPI group, vs one
      subject in the HFA-BDP and three subjects in the CFC-BDP groups; these were mild,
      and no subject discontinued treatment due to an adverse event. CONCLUSIONS:
      Fourteen days of treatment with MF-DPI 400 microg qd was associated with a
      significantly lesser decrease in the serum cortisol concentrations AUC(0-24)
      compared with HFA-BDP 200 microg MDI or CFC-BDP 400 microg MDI bid.

PMID- 16002919
TI  - Control of asthma under specialist care: is it achieved?
AB  - BACKGROUND: The goal of asthma treatment is control of asthma and good quality of
      life for asthmatic patients; however, many asthmatic patients experience symptoms
      and limitations. STUDY OBJECTIVES: To examine treatment outcome in asthmatic
      patients under specialist care. DESIGN: Multicenter, cross-sectional study.
      SETTING: Four large outpatient asthma clinics in teaching hospitals in three
      Greek cities. PATIENTS: Three hundred seventy-eight randomly selected patients
      with mild or moderate asthma (265 female patients; mean age, 42.3 years).
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients completed a questionnaire
      structured with eight domains covering patient characteristics, drug use at
      baseline and during exacerbations, regular follow-up, emergency visits, asthma
      control, symptoms, and limitations. Results show that the majority of patients
      have symptoms and limitations in their physical and social activities and have
      frequent exacerbations, while > 40% of patients think that their asthma is not
      well controlled. Most of our patients receive preventive medication (primarily
      inhaled corticosteroids, but less so long-acting beta2-agonists [LABAs] and
      leukotriene antagonists), increase their use of medication in case of
      exacerbations and have regular follow-up. However, the report shows that 48% of
      patients tried to reduce their medication dose, a fact implying that compliance
      is not always good. CONCLUSIONS: These data indicate that the goals of asthma
      treatment are not achieved, even under specialist care. Perhaps more effort
      should be invested in patient education while an increase in the use of LABAs and
      leukotriene antagonists, medications that have been shown to prevent exercise
      induced bronchoconstriction and improve quality of life, may help better asthma
      outcomes.

PMID- 16002920
TI  - Gastroesophageal reflux disease and asthma: a longitudinal study in UK general
      practice.
AB  - STUDY OBJECTIVES: Gastroesophageal reflux disease (GERD) and asthma are common
      causes for consultation in primary care, but the relationship between the two
      remains unclear. The aim of our study was to investigate the temporal
      relationship between first diagnoses of GERD and asthma in general practice.
      METHODS: We used the UK General Practice Research Database to identify a cohort
      of patients with a first diagnosis of GERD (n = 5,653) and another cohort of
      patients with a first diagnosis of asthma (n = 9,712) during 1996, which we
      compared with age-matched and sex-matched control cohorts drawn from the general
      population without either diagnosis. We investigated the incidence of a GERD
      diagnosis among the asthma patients and control subjects, and the incidence of an
      asthma diagnosis among the GERD patients and control subjects during a mean
      follow-up period of 3 years. We calculated the relative risk (RR) of these
      diagnoses using Cox regression analysis and examined the risk associated with
      medication use using nested case-control analysis. RESULTS: The incidence rates
      of GERD and asthma among the control cohorts were 4.4 and 3.8 per 1,000 person
      years, respectively. During the follow-up period, the RR of an incident asthma
      diagnosis in patients with a new diagnosis of GERD was 1.2 (95% confidence
      interval [CI], 0.9 to 1.6), while the RR of an incident GERD diagnosis among
      patients with a new diagnosis of asthma was 1.5 (95% CI, 1.2 to 1.8) after
      adjustment for age, sex, smoking, prior comorbidity, and number of health-care
      contacts. This increased risk was mainly seen during the first year of follow-up.
      The prior use of prescription medications for asthma and GERD had no significant
      effects on the risk of GERD and asthma diagnosis, respectively. CONCLUSIONS:
      Patients with asthma are at a significantly increased risk of developing GERD,
      mainly during the first year following diagnosis. A nonsignificant increase in
      the risk of developing asthma was evident among GERD patients. The relationship
      between GERD and asthma warrants further investigation.

PMID- 16002921
TI  - NRAMP1 gene polymorphism and susceptibility to nontuberculous mycobacterial lung
      diseases.
AB  - STUDY OBJECTIVES: Pulmonary disease caused by nontuberculous mycobacteria (NTM)
      may occur in patients with no underlying lung disease and no known
      immunodeficiency. The purpose of this study was to evaluate a potential role for
      natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms
      for human susceptibility to the NTM lung disease. DESIGN: A case-control study.
      SETTING: Tertiary university medical center. PARTICIPANTS: Forty-one adult
      patients with NTM lung disease (Mycobacterium avium complex infection, 18
      patients; Mycobacterium abscessus infection, 23 patients) were included in the
      study population. The diagnosis of NTM lung disease was made when the patients
      fulfilled the diagnostic criteria published by the American Thoracic Society. All
      patients had findings on high-resolution CT scans, such as bilateral
      bronchiectasis combined with multiple small nodules and branching linear
      structures, that were characteristic of the nodular bronchiectatic form of NTM
      lung disease. Fifty healthy individuals were selected as control subjects.
      RESULTS: Heterozygotes at intron 4 (469 + 14G/C) [INT4], codon 543 in exon 15
      (D543N), and 3' untranslated region (3'UTR) were observed at significantly higher
      frequencies in patients with NTM lung disease than in control subjects. The odds
      ratios (ORs) were 2.78 (95% confidence interval [CI], 1.12 to 6.89; p = 0.026)
      for INT4 G/C, 5.74 (95% CI, 1.48 to 22.30; p = 0.006) for D543 G/A, and 9.54 (95%
      CI, 2.49 to 36.53; p < 0.001) for 3'UTR TGTG+/del. Subjects who were heterozygous
      for two NRAMP1 polymorphisms in INT4 and D543N were particularly overrepresented
      among those with NTM lung disease, compared with those with the most common
      NRAMP1 genotype (OR, 10.88, 95% CI, 1.18 to 100.45; p = 0.035). There were no
      significant differences in the frequencies of INT4, D543N, and 3'UTR
      polymorphisms between the patients with M avium complex infection and those with
      M abscessus infection. CONCLUSIONS: These findings suggest that the NRAMP1
      genetic polymorphisms are associated with human susceptibility to NTM lung
      disease.

PMID- 16002922
TI  - Effect of nucleic acid amplification for Mycobacterium tuberculosis on clinical
      decision making in suspected extrapulmonary tuberculosis.
AB  - BACKGROUND: Laboratory-based studies have suggested the nucleic acid
      amplification test (NAAT) for Mycobacterium tuberculosis may be useful in
      diagnosing extrapulmonary tuberculosis. We sought to determine how clinicians in
      one hospital used results of the NAAT in clinical decision making in cases of
      suspected extrapulmonary tuberculosis. METHODS: We performed a retrospective
      analysis of all patients who underwent the NAAT on at least one nonsputum sample,
      excluding cerebrospinal fluid, from 1999 to 2001 in one large urban hospital. For
      these patients, we reviewed the hospital course, with particular attention to
      date of the NAAT and its influence on days treated with antituberculous
      medications and days to final diagnosis. RESULTS: Thirty-five patients with
      suspected tuberculosis who had undergone the NAAT on extrapulmonary specimens
      were identified. From three patients, NAAT results were nondiagnostic because of
      inhibitors, and they were excluded from the analysis, leaving 32 patients.
      Tuberculosis was ultimately diagnosed in 14 of these 32 patients. NAAT findings
      were positive in specimens from 12 of 14 patients with extrapulmonary
      tuberculosis and in 0 of 18 cases in which tuberculosis was excluded
      (sensitivity, 86%; specificity, 100%; positive predictive value, 100%; negative
      predictive value, 90%). In only 2 of 19 patients treated with antituberculous
      medications was the NAAT result used to determine the onset or discontinuation of
      therapy. In no instance was a negative NAAT result used by clinicians as
      definitive evidence that a patient did not have extrapulmonary tuberculosis; in
      all but one case, patients were continued on antituberculous therapy until final
      culture results were available. CONCLUSIONS: The NAAT proved to be a sensitive
      and specific test for detection of M tuberculosis in extrapulmonary specimens but
      did not weigh heavily in clinical decision making at our hospital. Judicious use
      of these tests may improve the accuracy and speed of diagnosis of extrapulmonary
      tuberculosis, while helping to eliminate unnecessary antituberculous treatment in
      patients without tuberculosis.

PMID- 16002923
TI  - Number of negative acid-fast smears needed to adequately assess infectivity of
      patients with pulmonary tuberculosis.
AB  - STUDY OBJECTIVES: To investigate the relationship between the number of negative
      acid-fast bacilli (AFB) smear results and infectivity of pulmonary tuberculosis
      (TB). DESIGN: Retrospective analysis. METHODS AND SUBJECTS: We examined 122 index
      cases in Harris County, TX, reported in 1998 and 1999. All cases had only
      negative AFB smear results during the infectious period and were categorized in
      two groups: group A consisted of cases with only one or two sputum specimens
      collected and processed, and group B consisted of cases with at least three
      sputum specimens or at least one bronchoscopic specimen. Tuberculin skin test
      (TST) results of contacts were ascertained from the results of contact
      investigations performed by the City of Houston Department of Health and Human
      Services, Tuberculosis Control Division. Univariate and multivariate analyses
      were done to explore index case and contact attributes associated with
      tuberculosis (TB) transmission using positive TST results of contacts as a
      measure of recent transmission. RESULTS: We found male gender and younger age of
      index cases along with Hispanic ethnicity of contacts to be independently
      associated with positive TST results, while younger contacts were less likely to
      be TST positive. Smear category of the index case (group A vs group B) was not
      independently associated with transmission. We also found that the first two
      sputum specimens in cases where three or more were performed yielded 90% of all
      positive culture results for Mycobacterium tuberculosis (MTB). CONCLUSIONS: We
      conclude that two sputum specimens negative for AFB stain are adequate for both
      assessing infectivity and for isolating MTB from patients with pulmonary TB.

PMID- 16002924
TI  - Isoniazid hepatotoxicity associated with treatment of latent tuberculosis
      infection: a 7-year evaluation from a public health tuberculosis clinic.
AB  - OBJECTIVES: To determine the overall incidence of isoniazid (INH) hepatotoxicity
      in a public health tuberculosis clinic over a 7-year period, and to determine if
      systematic, limited aspartate aminotransferase (AST) monitoring would be of
      benefit in detecting INH hepatotoxicity. METHODS: Evaluation of INH
      hepatotoxicity in adults aged > or = 25 years from a database maintained from
      fall 1996 to 2003 in a public health department clinic. Hepatotoxicity was
      defined as AST levels more than five times the upper limit of normal (ULN).
      RESULTS: Among 3,377 patients started on INH therapy, 19 patients had AST levels
      more than five times the ULN, or a rate of 5.6 per 1,000 patients. Only 1 of 19
      patients had prodromal symptoms associated with hepatotoxicity. After 1 month, 3
      months, and 6 months of therapy, the numbers of hepatotoxic events per 1,000
      patients were 2.75, 7.20, and 4.10. The age-specific numbers of hepatotoxic
      events per 1,000 patients were 4.40 for those from 25 to 34 years of age,
      inclusive; 8.54 for those between 35 to 49 years of age, inclusive; and 20.83 for
      those > or = 50 years old. Age > 49 years (p < 0.02) and baseline AST greater
      than ULN (p < 0.0003) were risk factors for hepatotoxicity. CONCLUSIONS:
      Consistent with earlier trials, INH hepatoxicity is age related. Our results
      suggest hepatotoxicity is also related to baseline AST greater than ULN. Moderate
      to-severe hepatotoxicity frequently occurs without symptoms, suggesting the value
      of more widespread AST monitoring.

PMID- 16002925
TI  - Lung cancer pathogenesis associated with wood smoke exposure.
AB  - BACKGROUND: Tobacco is considered the most important cause of lung cancer, but
      other factors could also be involved in its pathogenesis. The aim of the present
      work was to establish an association between wood smoke exposure and lung cancer
      pathogenesis, and to analyze the effects of wood smoke on p53 and murine double
      minute 2 (MDM2) protein expression. DESIGN: Blood samples were obtained from 62
      lung cancer patients, 9 COPD patients, and 9 control subjects. Of the 62 lung
      cancer patients, 23 were tobacco smokers (lung cancer associated with tobacco
      [LCT] group), 24 were exposed to wood smoke (lung cancer associated with wood
      smoke [LCW] group), and 15 could not be included in these groups. Western blot
      assays were performed to identify the presence of p53, phospho-p53, and murine
      double minute 2 (MDM2) isoforms in plasma samples. Densitometric analysis was
      used to determine the intensity of p53, phospho-p53, and MDM2 bands. RESULTS:
      Approximately 38.7% of the lung cancer patients examined had an association with
      wood smoke exposure, most of them women living in rural areas. Adenocarcinoma was
      present in 46.7% of these patients. The p53 and phospho-p53 proteins were
      significantly increased in LCW samples (56,536.8 +/- 4,629 densitometry units
      [DU] and 58,244.8 +/- 7,492 DU, respectively [+/- SD]), in comparison with the
      other groups. The 57-kD MDM2 isoform plasma concentration was very high in LCW
      and LCT samples (75,696.4 +/- 11,979 DU and 78,551.7 +/- 11,548 DU,
      respectively). MDM2-p53 complexes were present in a high concentration in control
      and COPD subjects. This allows p53 degradation and explains the low
      concentrations of p53 found in these groups. MDM2-phospho-p53 complexes were
      observed in COPD but not in the other samples. This correlates with the low
      concentration of p53 observed in the COPD group (13,657 +/- 2,012 DU), and could
      explain the different clinic evolution of this smoker population in comparison
      with the LCT subjects. CONCLUSION: This study suggests that there is a possible
      association of lung cancer with wood smoke exposure. Likewise, our findings
      demonstrate that wood smoke could produce similar effects on p53, phospho-p53,
      and MDM2 protein expression as tobacco.

PMID- 16002926
TI  - Chemotherapy for non-small cell lung cancer in elderly patients.
AB  - STUDY OBJECTIVE: To determine the appropriate chemotherapy regimen for
      inoperable, chemotherapy-naive non-small cell lung cancer (NSCLC) in elderly
      patients. SETTING: National teaching hospital in Taiwan. DESIGN: We
      retrospectively analyzed data from our clinical trials for a total of 270
      patients and compared them with the data from other studies, addressing the
      elderly in particular or providing subgroup information on age, to analyze the
      feasibility of current chemotherapy options for elderly patients and possible
      alternative approaches. RESULTS: The response rates and median survival times of
      fit elderly patients with NSCLC who were receiving appropriate new anticancer
      drugs for chemotherapy, including single-agent or combination treatment, were no
      worse than those of younger patients, and the response rates may have been even
      higher in the elderly patients, while survival time was slightly poorer in this
      group. The risk of adverse side effects, such as myelosuppression and peripheral
      neuropathy, may be higher in elderly patients, who also visit the hospital more
      frequently. Some items on the lung cancer symptom scale for elderly patients were
      rated as being slightly worse than those for younger patients after chemotherapy.
      CONCLUSION: Advanced age alone should not preclude chemotherapy. New single-agent
      drugs, and non-platinum-based or platinum-based doublets, can all be considered
      as appropriate treatment for selected fit elderly patients with advanced NSCLC.

PMID- 16002927
TI  - Immunohistochemical KIT (CD117) expression in thymic epithelial tumors.
AB  - STUDY OBJECTIVES: It is sometimes very difficult both clinically and
      pathologically to distinguish thymic epithelial tumors from primary lung
      carcinoma with massive anterior mediastinal involvement. The expression of KIT
      (CD117) in thymic epithelial tumors was investigated in order to evaluate its
      usefulness as a marker supporting differential diagnosis and choice of therapy.
      METHODS: We examined the immunohistochemical expression of KIT in 70 resected
      thymic epithelial tumors (thymomas, 50; thymic carcinomas, 20) that had been
      reclassified on the basis of the World Health Organization histologic
      classification system. We also compared the expression of KIT and CD5 in 20
      thymic carcinomas with their expression in 20 resected pulmonary squamous cell
      carcinomas that were spreading directly into the mediastinum. RESULTS: Of the 50
      thymomas, only 2 (4%) showed positive immunoreactivity for KIT (type A thymoma,
      1; type B3 thymoma, 1), whereas 16 of the 20 thymic carcinomas (80%) showed
      positive immunoreactivity. Testing was positive for CD5 in 14 of the 20 thymic
      carcinomas (70%). In the pulmonary squamous cell carcinomas, in contrast, the
      immunohistochemical expression of KIT and CD5 was found in only 4 of 20
      carcinomas (20%) and 3 of 20 carcinomas (15%), respectively. Furthermore, of the
      40 specimens examined (either thymic or lung carcinoma) all 13 that were positive
      for both KIT and CD5 were thymic carcinomas, and 13 of the 16 that were negative
      for both were lung carcinomas. CONCLUSION: KIT expression is a useful
      immunohistochemical marker for the diagnosis of thymic carcinoma, and its
      examination in combination with CD5 immunohistochemistry would greatly help in
      the differential diagnosis of primary thymic carcinoma from pulmonary squamous
      cell carcinoma. Further investigations at a genetic level should be encouraged,
      not only to define the role of KIT in the oncogenesis of thymic epithelial
      tumors, but also to establish target-based therapy.

PMID- 16002928
TI  - Impaired respiratory and skeletal muscle strength in patients prior to
      hematopoietic stem-cell transplantation.
AB  - STUDY OBJECTIVES: The primary aim was to determine if respiratory and skeletal
      muscle strength and submaximal exercise capacity were reduced in subjects prior
      to sibling- or unrelated-donor hematopoietic stem-cell transplantation (HSCT).
      DESIGN: Prospective observational study. SETTING: Tufts-New England Medical
      Center, a tertiary referral center in Boston, MA. PATIENTS: All patients (n = 56)
      undergoing either sibling- or unrelated-donor HSCT from January 1, 2002, to
      December 31, 2002. MEASUREMENTS: Demographic data, chemotherapy burden, pulmonary
      function tests (PFTs), maximal inspiratory muscle strength (PImax), maximal
      expiratory muscle strength (PEmax), dominant hand grip strength (GS), 6-min walk
      test (6MWT), and survival as of May 21, 2004. RESULTS: PImax was reduced to < 80%
      predicted in 42% of subjects and to < 60% predicted in 18% of subjects. PEmax was
      reduced to < 80% predicted in 89% of subjects and to < 60% of predicted in 80% of
      subjects. A significant correlation was observed between PImax and PEmax (r =
      0.65, p < 0.0001). GS was reduced to < 80% predicted in 39% of subjects and < 60%
      predicted in 15% of subjects. The 6MWT was reduced to < 80% predicted in 58% of
      subjects and to < 60% predicted in 9.6% of subjects. Diffusing capacity of the
      lung for carbon monoxide (Dlco) was the only PFT that was significantly
      correlated with 6MWT distance (r = 0.44, p = 0.015). The mean calculated load of
      chemotherapy was 14.8 +/- 16.5 U (+/- SD). The mean time elapsed from date of
      hematologic diagnosis to date of HSCT was 874 +/- 1,109 days. The median survival
      of the cohort was 374 days (95% confidence interval, 177 to 665 days).
      Respiratory or skeletal muscle strength, 6MWT distance, or calculated burden of
      chemotherapy did not predict survival. CONCLUSIONS: Respiratory and skeletal
      muscle strength and submaximal exercise capacity are reduced in a significant
      percentage of patients prior to undergoing HSCT. These observations may help
      explain musculoskeletal weakness that has been reported in the posttransplant
      period.

PMID- 16002929
TI  - Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell
      transplantation for leukemia.
AB  - STUDY OBJECTIVES: Reported risk factors for bronchiolitis obliterans (BO) in
      allogeneic hematopoietic stem-cell transplant recipients come from modest-sized
      studies and are limited to experiences of single institutions. We sought to
      identify risk factors for BO using data from the International Bone Marrow
      Transplant Registry. METHODS: Registry data on 6,275 adult patients with leukemia
      who received human leukocyte antigen-identical sibling transplants from 1989 to
      1997 and survived at least 100 days after transplantation were evaluated for the
      study. Risk factors for BO were analyzed using proportional hazards regression.
      RESULTS: Seventy-six patients were found to have BO, with an incidence rate of
      1.7% at 2 years after transplantation. The Kaplan-Meier estimate of median time
      to onset of BO was 431 days. Histologic evaluation was performed in 36 patients
      (47%). In 28 patients (37%), diagnosis was based on pulmonary function tests, CT
      scans of the chest, or a combination of both. On multivariate analysis, the
      factors that were associated with an increased risk for BO included the
      following: peripheral blood-derived stem cell, a busulfan-based conditioning
      regimen, interval from diagnosis to transplant > or = 14 months, female donor to
      male recipient sex match, prior interstitial pneumonitis, and an episode of
      moderate-to-severe acute graft-vs-host disease (GVHD). CONCLUSION: In addition to
      corroborating previously reported risk factors, such as acute GVHD and a busulfan
      based conditioning regimen, we found that peripheral blood stem-cell
      transplantation, long duration to transplant, female donor to male recipient, and
      a prior episode of interstitial pneumonitis are associated with an increased risk
      for BO.

PMID- 16002930
TI  - Septic pulmonary embolism: presenting features and clinical course of 14
      patients.
AB  - BACKGROUND: Septic pulmonary embolism (SPE) is an uncommon disorder with an
      insidious onset and is difficult to diagnose. STUDY OBJECTIVES: To characterize
      the presenting features and clinical course of patients with SPE. DESIGN:
      Retrospective study. SETTING: Tertiary care, referral medical center. PATIENTS:
      Fourteen subjects with SPE diagnosed during a 6-year period between 1996 and
      2002. INTERVENTIONS: None. RESULTS: The median age of these patients was 37.5
      years (range, 14 to 81 years) and included five women. Presenting symptoms
      included fever (93%), dyspnea (36%), pleuritic chest pain (29%), cough (14%), and
      hemoptysis (7%). The median duration of symptoms before diagnosis was 18 days
      (range, 5 to 180 days). A potential source or underlying condition that
      predisposed to SPE was identified in all 14 patients and included Lemierre
      syndrome (4 patients), central venous catheter infection (3 patients), prosthetic
      cardiac valve (2 patients), and pacemaker infection (2 patients). Two patients
      had a focal extrapulmonary infection, and one patient was an IV drug user. Most
      common pathogens were staphylococcal species (eight patients) and fusobacterium
      (four patients). Chest radiographic presentation was usually nonspecific, but CT
      was more helpful and revealed multiple nodular opacities peripherally, often with
      cavitation. Transesophageal echocardiography was performed in eight patients and
      demonstrated infectious vegetations in four cases. Aside from antimicrobial
      therapy and removal of infected devices, the management of these patients
      included cardiac surgery (two patients), thoracoscopic surgery with decortication
      (one patient), and tube thoracostomy (one patient). All 14 patients recovered
      from their illness. CONCLUSIONS: We conclude that SPE presents with variable and
      often nonspecific clinical and radiographic features. The diagnosis is usually
      suggested by the presence of a predisposing factor, febrile illness, and CT
      findings of multiple, nodular lung infiltrates peripherally, with or without
      cavitation.

PMID- 16002931
TI  - Low sensitivity of a nested polymerase chain reaction in oropharyngeal washings
      for the diagnosis of pneumocystis pneumonia in HIV-infected patients.
AB  - STUDY OBJECTIVE: To compare the relative yield and diagnostic utility of the
      polymerase chain reaction (PCR) analysis for Pneumocystis jirovecii DNA in
      oropharyngeal washings using transbronchial biopsy (TBBx) and BAL as "gold
      standards." DESIGN: Prospective study. SETTING: Academic tertiary center.
      PATIENTS: Oropharyngeal washes were obtained in 50 consecutive patients with
      clinical pneumocystis pneumonia (PCP). Because of varying clinical severity, not
      all patients tolerated bronchoscopy. Thirty-five patients underwent TBBx, and 48
      patients underwent BAL. METHODS: DNA extracted from oropharyngeal washings and
      BAL was subjected to a nested PCR test using primers for the large subunit
      mitochondrial ribosomal RNA of P jirovecii. Oropharyngeal washings were compared
      with BAL PCR and TBBx. RESULTS: Sixteen of the 35 TBBx procedures had positive
      results for PCP (46%). Oropharyngeal washings yielded positive results for
      pneumocystis in 7 of the 16 patients (sensitivity, 44%; specificity, 79%). Thirty
      five of 48 patients (73%) had positive PCR results on BAL analysis. The relative
      yield of the PCR in oropharyngeal washes compared with BAL fluid was 40% (14 of
      35 washes), giving a sensitivity of 40% and specificity of 77%. CONCLUSION: PCR
      DNA amplification of oropharyngeal washings in HIV-seropositive subjects has a
      low sensitivity and specificity for the diagnosis of PCP.

PMID- 16002932
TI  - Comparison of levofloxacin and cefotaxime combined with ofloxacin for ICU
      patients with community-acquired pneumonia who do not require vasopressors.
AB  - STUDY OBJECTIVES: To evaluate the efficacy and tolerability of levofloxacin (L)
      as monotherapy in patients with severe community-acquired pneumonia (CAP) in
      comparison with therapy using a combination of cefotaxime (C) plus ofloxacin (O).
      DESIGN: Prospective, randomized 1:1, comparative, open, parallel-group study.
      SETTING: Multinational study with 149 sites. PATIENTS: A total of 398 randomized
      patients who had been admitted to the ICU with severe CAP without shock,
      including 308 patients in a modified intent-to-treat population and 271 patients
      in the per-protocol (PP) population (L group, 139 patients; C + O group, 132
      patients). INTERVENTIONS: Therapy with levofloxacin (500 mg IV, q12h) vs therapy
      with a C + O combination (C, 1g IV, q8h; O, 200 mg IV, q12h) for 10 to 14 days.
      MEASUREMENTS AND RESULTS: The main end point was the clinical efficacy at the end
      of treatment (ie, the test-of-cure [TOC] visit). The statistical hypothesis was
      the noninferiority of L therapy to C + O therapy with a 2.5% alpha risk
      (unilateral) and a 15% maximum set difference. At the TOC visit, a clinical
      success was observed in 79.1% of patients (L group) and 79.5% of patients (C + O
      group) in the PP population (difference, -0.4%; 95% confidence interval [CI], 
      10.79 to 9.97% without adjustment for simplified acute physiology score [SAPS] II
      at inclusion; difference, -0.3%; 95% CI, -10.13 to 9.58% with adjustment for SAPS
      II). A satisfactory bacteriologic response was present in 73.7% of L group
      patients and 77.5% of C + O group patients, including responses of 75.7% and
      70.3%, respectively, in the L group and C + O group in the Streptococcus
      pneumoniae-documented population. In the safety analysis, 20 patients in the L
      group (10.3%) and 16 patients in the C + O group (8.0%) experienced at least one
      adverse event that was considered to be treatment-related. CONCLUSION: L therapy
      was at least as effective as the combination therapy of C + O in the treatment of
      a subset of patients with CAP requiring ICU admission. This conclusion cannot be
      extrapolated to patients requiring mechanical ventilation or vasopressors (ie,
      those patients in shock).

PMID- 16002933
TI  - Effects of partial isothermic immersion on the spirometry parameters of
      tetraplegic patients.
AB  - STUDY OBJECTIVES: Our objective was to compare under controlled conditions the
      effect of immersion on spirometry parameters of patients with tetraplegia vs
      those of normal individuals. DESIGN AND PATIENTS: Twenty-three otherwise well
      tetraplegic subjects were compared to a control group of 11 similar healthy
      subjects before and during 5 to 15 min of isothermal immersion in water to
      shoulder level. RESULTS: Measured at baseline, tetraplegic subjects exhibited
      significant pulmonary restriction, characterized by a mean FVC of 54.9 +/- 14.6%
      of the predicted value (range, 23.2 to 80.4%), whereas all controls subjects had
      > 80% of predicted values. Immersion increased the FVC of tetraplegic patients an
      average of 18.4 +/- 18.7% above basal measurements, while that of the control
      group worsened (DeltaFVC, - 8.8 +/- 4.4%). Among the tetraplegic patients, the
      lower the preimmersion vital capacity, the greater the percentage of improvement
      following immersion (r = 0.79; 95% confidence interval, - 0.91 to - 0.56; p <
      0.0001). No relationship was found between the time elapsed since cervical cord
      injury or its level and the degree of improvement. CONCLUSIONS: Water activities
      play an important role in the rehabilitation of patients with spinal cord injury.
      Immersion in isothermal water at shoulder level, under strictly controlled
      experimental conditions, reduces the vital capacity of normal individuals, while
      it improves in a group of patients with tetraplegia. The observed phenomenon
      seems to be mediated by an improvement in breathing mechanics, impaired by
      cervical cord injury.

PMID- 16002934
TI  - Influence of different trigger techniques on twitch mouth pressure during
      bilateral anterior magnetic phrenic nerve stimulation.
AB  - BACKGROUND: The trigger has a key role when assessing the twitch mouth pressure
      (Tw Pmo), since a "gentle" inspiratory or expiratory effort is needed for
      triggering to ensure an open glottis during twitch, but which also guarantees
      only very mild changes of transdiaphragmatic pressure following changes in lung
      volume. STUDY OBJECTIVES: To test if different trigger mechanisms cause different
      Tw Pmo values, if the predefined trigger criteria were accomplished, and if the
      breathing maneuver during triggering can influence the Tw Pmo. DESIGN:
      Experimental study. SETTING: Respiratory muscle and lung function laboratory of a
      university hospital. PARTICIPANTS: Twenty healthy men (mean age, 25.6 +/- 1.2
      years [+/- SD]; mean FEV(1), 105.9 +/- 11.5% of predicted). MEASUREMENTS: Tw Pmo
      produced by bilateral anterior magnetic phrenic nerve stimulation was measured
      using an inspiratory flow trigger (40 mL/s), an inspiratory pressure trigger, and
      an expiratory pressure trigger (3.75 mm Hg). All trigger criteria were
      controlled. RESULTS: Unusable pressure-time curves occurred in 40% during
      expiratory triggering, but not during inspiratory triggering. For inspiratory
      pressure (flow) triggering, 10% (30%) of the predefined trigger criteria were
      exceeded by 50%, indicating that a "gentle" inspiratory effort was not warranted.
      The Tw Pmo was higher during inspiratory compared to expiratory triggering
      (analysis of variance, p < 0.05). The Tw Pmo during inspiratory pressure and flow
      triggering were comparable and significantly correlated (r = 0.70, p < 0.0001).
      The time between start of inspiration and trigger release, and the pressure-time
      product during that period ranged widely, but this could not predict the Tw Pmo
      (multiple linear regression). CONCLUSIONS: The trigger technique influences the
      Tw Pmo with higher values during inspiratory compared to expiratory triggering.
      Expiratory triggering more often produced unusable pressure-time curves.
      Inspiratory flow and pressure triggering is comparably useful in healthy
      subjects, but this might be different in patients. The trigger criteria need to
      be controlled to warrant a gentle breathing effort.

PMID- 16002935
TI  - Safety of capsaicin cough challenge testing.
AB  - BACKGROUND: Capsaicin, the pungent extract of red peppers, has achieved
      widespread use in clinical research because it induces cough in a dose-dependent
      and reproducible manner. Although > 2 decades of experience has led investigators
      to consider capsaicin cough challenge testing a safe diagnostic modality, this
      issue has not been specifically addressed in the literature. STUDY OBJECTIVES: To
      review the published experience with capsaicin inhalation challenge testing in
      terms of safety. DESIGN: Literature review and personal communication with study
      authors. SETTING: Academic medical center. RESULTS: One hundred twenty-two
      published studies since 1984 described 4,833 subjects (4,374 adults, 459
      children) undergoing capsaicin cough challenge, with no serious adverse events
      reported. Subjects included healthy volunteers as well as patients with asthma,
      COPD, pathologic cough, and other respiratory conditions. Minor complaints
      described in a small fraction of studies consisted mainly of transient throat
      irritation. Personal communication with the authors of > 90% of the studies
      confirmed an absence of any serious adverse events. Furthermore, these
      investigators have performed thousands of additional capsaicin challenge studies
      not reported in the literature, also without any associated serious adverse
      events. CONCLUSIONS: A review of the 20-year clinical experience has failed to
      uncover a single serious adverse event associated with capsaicin cough challenge
      testing in humans. Given the need for better antitussive therapies, capsaicin
      represents a vital component of future scientific inquiry in the field of cough.

PMID- 16002936
TI  - Interferon-gamma1b therapy in idiopathic pulmonary fibrosis: a metaanalysis.
AB  - CONTEXT: Despite the investigation of multiple therapeutic options, idiopathic
      pulmonary fibrosis (IPF) remains a devastating, progressively fatal disease. Much
      interest has focused on the use of interferon (IFN)-gamma1b therapy, but the
      efficacy of this treatment has not been proven. OBJECTIVE: To determine whether
      IFN treatment reduces mortality in patients with IPF. DESIGN: A meta-analysis of
      randomized controlled trials evaluating the use of IFN-gamma1b as treatment for
      IPF. MAIN OUTCOME MEASURE: Mortality in patients treated with IFN-gamma1b was
      compared to mortality in patients treated with control therapies. RESULTS: A
      total of three studies involving 390 patients was included in the analysis. IFN
      gamma1b therapy was associated with reduced mortality (hazard ratio [HR], 0.418;
      95% confidence interval [CI], 0.253 to 0.690; p = 0.0003). A comparison of
      mortality at different time points revealed that IFN-gamma1b therapy was
      associated with significantly reduced mortality at 1 year (0.0861; 95% CI, 0.0244
      to 0.1478; p = 0.0063), 18 months (0.1682; 95% CI, 0.1065 to 0.2299; p < 0.0001),
      650 days (0.1939; 95% CI, 0.1386 to 0.2492; p < 0.0001), and 2 years (0.2652; 95%
      CI, 0.1652 to 0.3652; p < 0.0001). CONCLUSION: When the results of multiple
      studies are combined in a meta-analysis, IFN-gamma1b therapy is associated with
      reduced mortality.

PMID- 16002937
TI  - Relationship of environmental exposures to the clinical phenotype of sarcoidosis.
AB  - STUDY OBJECTIVES: Sarcoidosis is a granulomatous disorder with heterogeneous
      clinical manifestations, which are potentially reflective of a syndrome with
      different etiologies leading to similar histologic findings. We examined the
      relationship between environmental and occupational exposures, and the clinical
      phenotype of sarcoidosis. DESIGN: We performed a cross-sectional study of
      incident sarcoidosis cases that had been identified by A Case Control Etiologic
      Study of Sarcoidosis. Subjects were categorized into the following two groups:
      (1) pulmonary-only disease; and (2) systemic disease (with or without pulmonary
      involvement). Logistic regression was used to examine the associations of
      candidate exposures with clinical phenotype. SETTING: Ten academic medical
      centers across the United States. PATIENTS: The current study included 718
      subjects in whom sarcoidosis had been diagnosed within 6 months of study
      enrollment. Patients met the following criteria prior to enrollment: (1) tissue
      confirmation of noncaseating granulomas on tissue biopsy on one or more organs
      within 6 months of study enrollment with negative stains for acid-fast bacilli
      and fungus; (2) clinical signs or symptoms that were consistent with sarcoidosis;
      (3) no other obvious explanation for the granulomatous disease; and (4) age > 18
      years. MEASUREMENTS AND RESULTS: Several exposures were associated with
      significantly less likelihood of having extrapulmonary disease in multivariate
      analysis, including agricultural organic dusts and wood burning. The effects of
      many of these exposures were significantly different in patients of different
      self-defined race. CONCLUSIONS: The differentiation of sarcoidosis subjects on
      the basis of clinical phenotypes suggests that these subgroups may have unique
      environmental exposure associations. Self-defined race may play a role in the
      determination of the effect of certain exposures on disease phenotypes.

PMID- 16002938
TI  - Effectiveness of hospital-based smoking cessation.
AB  - STUDY OBJECTIVES: Smoking cessation for current smokers is a health-care
      imperative. It is not clear which approaches to smoking cessation are the most
      effective in the hospital setting and which factors predict long-term abstinence.
      We hypothesized that a hospital-based smoking cessation program involving
      behavioral modification and support would provide an effective intervention for
      smoking cessation. DESIGN: Prospective cohort study. SETTING: Smoking cessation
      clinics in a tertiary referral, cardiothoracic hospital. PATIENTS OR
      PARTICIPANTS: Two hundred forty-three smokers and 187 never-smoker control
      subjects. INTERVENTIONS: Smokers underwent specific sessions of individual
      counseling on behavioral modification, including written information, advice
      about quit aids, and support during the quit attempt. Abstinence was confirmed by
      exhaled carbon monoxide measurements. MEASUREMENTS AND RESULTS: Compared to never
      smoker control subjects, smokers were more likely to have grown up with a smoking
      father or siblings, and to currently live or socialize with other smokers. Two
      hundred sixteen smokers attended at least two sessions of the smoking cessation
      program. Of these, 25% were unavailable for follow-up at 12 months and were
      assumed to be smoking. The point prevalence abstinence rate at 12 months was 32%.
      Independent factors associated with abstinence at 12 months were self-belief in
      quitting ability, having a heart condition, growing up without siblings who
      smoked, and increasing number of pack-years. CONCLUSIONS: This prospective study
      has demonstrated that this hospital-based smoking cessation program was as
      effective as programs in other settings. Social and psychological factors were
      associated with a greater chance of abstinence.

PMID- 16002939
TI  - Large lungs in divers: natural selection or a training effect?
AB  - BACKGROUND: Normal spirometry is required for medical clearance of professional
      divers in many countries. Divers frequently have unusually large lung volumes
      associated with a low ratio of FEV(1) to FVC (FEV(1)%), suggestive of obstructive
      airways disease. We retrospectively analyzed the records of divers in the Israeli
      Navy with a low FEV(1)% who fulfilled the criteria for large lungs, to determine
      whether this might be the effect of training or natural selection. We also
      investigated changes in pulmonary function in relation to diving experience.
      METHODS: A total of 171 divers with FEV(1)% < 80% on simple spirometry were
      evaluated. We conducted a retrospective analysis of lung function data for those
      subjects who met the criteria for large lungs. RESULTS: One hundred nine of 171
      divers with low FEV(1)% met the criteria for large lungs and were included in the
      study. Their average age was 25 years (range, 18 to 44 years), and their mean
      diving experience was 7 years (range, 0 to 26 years). No difference was found in
      FVC values between experienced and inexperienced divers. The mean forced
      expiratory flow at 50% of vital capacity was significantly reduced in the most
      experienced group compared with the novice or less experienced divers. No
      difference was found in the diffusing capacity of the lung for carbon monoxide
      between experienced and inexperienced divers. CONCLUSIONS: We suggest that large
      lungs may represent part of the natural selection for diving, rather than a
      training effect. Prolonged diving experience may result in the development of
      small airways disease.

PMID- 16002941
TI  - Similar long-term survival of elderly patients with non-small cell lung cancer
      treated with lobectomy or wedge resection within the surveillance, epidemiology,
      and end results database.
AB  - STUDY OBJECTIVES: To determine the effect of age and type of surgery on long-term
      survival in patients with early-stage non-small cell lung cancer (NSCLC). DESIGN
      AND PATIENTS: A total of 14,555 patients who were > or = 20 years of age with
      stage I or II primary NSCLC and had been registered in the Surveillance,
      Epidemiology, and End Results Database from 1992 to 1997 were analyzed. Age was
      grouped into the following three categories: < 65 years (n = 5,057; 35%); 65 to
      74 years (n = 6,073; 42%); and > or = 75 years (n = 3,425; 23%). Log-rank tests
      and Cox regression models were used for crude and adjusted survival analyses.
      MEASUREMENTS AND RESULTS: A total of 8,080 men (55%) and 6,475 women (mean [+/-
      SD] age, 67.3 +/- 9.8 years) with stage I NSCLC (83%) or stage II NSCLC were
      analyzed. Curative surgery was performed in 4,669 patients (92%) who were < 65
      years of age (youngest), 5,219 patients (86%) who were 65 to 74 years of age
      (intermediate age), and 2,382 patients (70%) who were > or = 75 years of age
      (elderly) [p < 0.0001]. Thirty percent of the elderly patients were denied
      surgery or were offered only palliative surgery, in contrast with 8% among the
      youngest patients (p < 0.0001). Limited resections increased from 8% in young
      patients to 17% in the elderly (p < 0.0001). Survival decreased with age. The
      median survival times were 71, 47, and 28 months, respectively, for patients <
      65, 65 to 74, and > or = 75 years of age (p < 0.0001). The results were unchanged
      after adjusting for sex, type of surgery, histology, and stage of disease. For
      the young patients, lobectomies conferred better survival times than limited
      resections after 2 years. However, there was no difference in survival between
      lobectomies and limited resections in terms of survival time for the elderly
      patients. The statistical difference in long-term survival between those patients
      undergoing lobectomies and those undergoing limited resections disappeared at 71
      years. CONCLUSIONS: Age is an independent predictor of postsurgical survival in
      NSCLC patients, even after adjustment for significant covariates. Curative
      surgery is performed less frequently in elderly patients. Among younger patients
      undergoing curative surgery, lobectomies are more commonly performed and confer a
      significant survival benefit over limited resections. This benefit, however, is
      not evident for patients > 71 years of age.

PMID- 16002940
TI  - Coagulation activation and organ dysfunction following cardiac surgery.
AB  - STUDY OBJECTIVES: Cardiac surgery with cardiopulmonary bypass (CPB) is associated
      with major inflammatory triggers that cause marked activation of the
      microcirculation. This inflammatory response is associated with significant organ
      dysfunction. How this response causes organ dysfunction is not well understood;
      consequently, few interventions exist to prevent or treat it. In other acute
      inflammatory conditions, such as sepsis, increased coagulation activation in the
      microcirculation may be a cause of organ injury. We documented the association
      between coagulation activation and organ dysfunction to investigate whether
      coagulation activation also plays a role in organ injury following cardiac
      surgery with CPB. DESIGN: Prospective study of 30 patients undergoing cardiac
      surgery with CPB. Prothrombin fragment (PTF) 1 + 2 and plasminogen activator
      inhibitor (PAI) activity were measured, and levels correlated with postoperative
      measures of organ function including the left-ventricular stroke work index, the
      Pao(2)/fraction of inspired oxygen (Fio(2)) ratio, and creatinine levels.
      RESULTS: PTF levels increased eightfold (p < 0.05), and PAI activity increased
      threefold (p < 0.05) over the first 4 h after CPB. PTF levels were correlated
      with deteriorations in the left-ventricular stroke work index (p = 0.04), the
      Pao(2)/Fio(2) ratio (p = 0.02), and creatinine levels (p = 0.02). CONCLUSIONS:
      Levels of coagulation activation are associated with markers of postoperative
      organ dysfunction. Additional studies are warranted to investigate whether
      strategies that limit coagulation activation are associated with reductions in
      postoperative organ dysfunction.

PMID- 16002942
TI  - Surgical treatment of thoracic empyema in HIV-infected patients: severity and
      treatment modality is associated with CD4 count status.
AB  - OBJECTIVES: Patients infected with HIV have an increased propensity for
      developing thoracic empyemas secondary to their susceptibility to polymicrobial
      pulmonary infections. We performed an assessment of the clinical outcomes of HIV
      patients undergoing surgical treatment of thoracic empyemas and reviewed the
      microbiology of these infections. METHODS: We completed a retrospective analysis
      of the patients who had been referred for surgical treatment of thoracic empyemas
      over an 11-year period, ending in 2002. The patients were treated at a major
      metropolitan medical teaching facility that cares for a substantial number of HIV
      positive patients. RESULTS: Twenty-one HIV-infected patients underwent surgical
      treatment of thoracic empyemas. There were no immediate deaths. Sixty-two percent
      of the patients had CD4 counts of < 200 cells/microL. Eight patients had
      postoperative complications. Six of the patients with complications had CD4
      counts of < 200 cells/microL. Patients with lower CD4 counts were at risk for
      mycobacterial and fungal infections. Additionally, they often had complex
      empyemas that were not favorable for treatment by video-assisted thoracic
      surgery. Therefore, these patients often required surgery with lung resection,
      which necessitated longer periods of postoperative chest tube drainage.
      CONCLUSIONS: Surgeons can obtain satisfactory operative outcomes when treating
      thoracic empyemas in HIV patients; however, the treatment strategy should be
      individualized. Patients with CD4 counts of < 200 cells/microL more commonly have
      complex empyemas that require surgery with open decortication and drainage.
      Although these patients have a higher incidence of postoperative complications,
      we think that HIV patients with thoracic empyemas can be safely and effectively
      treated with surgical techniques.

PMID- 16002943
TI  - Impact of induction concurrent chemoradiotherapy on pulmonary function and
      postoperative acute respiratory complications in esophageal cancer.
AB  - STUDY OBJECTIVE: To evaluate the effects of induction concurrent
      chemoradiotherapy (cCRT) on pulmonary function and postoperative acute
      respiratory complications (PARCs). DESIGN: A retrospective review of our patients
      treated with induction cCRT to determine the impact on pulmonary function and
      identify predictors of PARCs. Correlations were sought between patient
      demographics, clinical characteristics, pre-cCRT and post-cCRT pulmonary
      function, radiotherapy dose, chemotherapy agents, and the development of PARCs.
      PARTICIPANTS: One hundred fifty-five patients treated in three separate clinical
      trials were identified; 47 patients received 30 Gy (150 cGy bid) of radiation
      concurrently with a single course of cisplatin/5-fluorouracil (5FU), and 108
      patients received 45 Gy (150 cGy bid in a split course) concurrent with two
      courses of either cisplatin/5FU (n = 69) or cisplatin/paclitaxel (n = 39).
      Esophagectomy was performed in 141 of these 155 patients following cCRT. RESULTS:
      cCRT was only associated with significant worsening of the diffusion capacity of
      the lung for carbon monoxide (Dlco), which decreased a median of 21.7% in the 45
      Gy group (p = 0.007), and 8.6% in the 30-Gy group (p = 0.07). This Dlco decrease
      was statistically greater in the 45-Gy group than in the 30-Gy group (p = 0.02).
      PARCs developed in 18 patients. Percentage of predicted FEV(1) and FVC, both
      before and after cCRT, were both significantly higher in patients without PARCs
      than in patients with PARCs (p = 0.031 and p = 0.010, respectively). Post-cCRT
      Dlco was also significantly worse in patients with PARCs (p = 0.002). PARCs
      occurred significantly more often among those treated with 45 Gy (17 of 102
      patients) compared to those treated with 30 Gy (1 of 39 patients) [p = 0.025]. In
      the 18 patients with PARCs, the median survival was only 2.1 months. This was
      significantly less than the 16.4-month median survival in the 123 patients who
      did not have PARCs (p = 0.001). CONCLUSIONS: In patients treated with induction
      cCRT, higher radiation doses result in increasing impairment of gas exchange.
      PARCs were more likely in those patients with lower lung volumes, lower post-cCRT
      Dlco, and in those receiving higher radiation doses. These acute respiratory
      complications were also associated with a significant reduction in patient
      survival.

PMID- 16002944
TI  - Different cycle ergometer outcomes in severely obese men and women without
      documented cardiopulmonary morbidities before bariatric surgery.
AB  - STUDY OBJECTIVES: The number of severely obese patients undergoing bariatric
      surgery is increasing. No incremental cycle ergometer data are available in this
      category of patients. The current study was undertaken to provide information and
      to compare outcomes between severely obese men and women during physical
      exercise. DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-two men and 34
      women, all with a body mass index (BMI) of at least 40 kg/m(2), were selected
      from among persons participating in a dedicated weight management program that
      was carried out in the outpatient clinic of a large teaching hospital.
      MEASUREMENTS AND RESULTS: Body composition was estimated with bioelectrical
      impedance. Oxygen uptake (Vo(2)) was obtained by breath-by-breath minute
      ventilation (ventilated hood) and was measured under resting energy expenditure
      (REE) conditions. Endurance was measured with an incremental cycle ergometer
      test. Male and female groups were balanced for mean (+/- SD) age (42.7 +/- 7.6 vs
      41.8 +/- 8.9 years, respectively), BMI (43.0 +/- 4.9 vs 41.3 +/- 5.2 kg/m(2),
      respectively), and fat weight (55.5 +/- 14.0 vs 56.8 +/- 2.2 kg, respectively).
      Fat-free mass (FFM), FFM index, fasting blood glucose level, insulin level, REE,
      and Vo(2) at rest and during subjective maximal endurance were higher in the male
      group. However, maximal Vo(2) (women, 119 +/- 19% predicted; men, 92 +/- 16%
      predicted) and anaerobic threshold were higher in the female group (women, 64 +/-
      12% predicted; men, 48 +/- 76% predicted, respectively; p < 0.0001). CONCLUSIONS:
      Severely obese men were more carbohydrate-intolerant and sustained less physical
      endurance than was predicted according to standards in comparison with obese
      women. The cycle ergometer data indicated that male gender was associated with
      less physical fitness.

PMID- 16002945
TI  - Adverse effects of ribavirin and outcome in severe acute respiratory syndrome:
      experience in two medical centers.
AB  - STUDY OBJECTIVES: To assess the effect of ribavirin-induced anemia on the outcome
      of severe acute respiratory syndrome (SARS). DESIGN: A retrospective
      observational study. SETTING: Two medical centers in Taiwan. PATIENTS: Forty-four
      patients with SARS who received ribavirin and 7 patients with SARS who did not
      receive ribavirin. MEASUREMENTS AND RESULTS: The mean peak C-reactive protein and
      lactate dehydrogenase levels were higher in SARS patients who were receiving
      ribavirin therapy than in SARS patients who were not receiving ribavirin therapy.
      The mortality was also higher, but the difference was not statistically
      significant. On multivariate analysis, hemoglobin level was an independent
      prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence
      interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of
      SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after
      therapy with the antiviral drug was started. Patients with a drop in hemoglobin
      level of > 2 g/dL had a significantly higher mortality rate than the other
      patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients;
      39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic
      patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%)
      required a blood transfusion. The mean slope of the hemoglobin decrease was
      significantly steeper (p = 0.001) in hypoxemic patients with SARS who were
      receiving ribavirin than in the nonhypoxemic patients with SARS who were
      receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving
      ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of
      17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died.
      The combination of hypoxia with anemia was thus significantly associated with a
      higher mortality (p < 0.001). CONCLUSIONS: Hypoxia combined with anemia increased
      the risk for death in SARS patients. Unless ribavirin can be shown to be
      effective against SARS-coronavirus, the risk of anemia posed by this drug argues
      against its use in SARS patients.

PMID- 16002946
TI  - Respiratory microbiology patterns within the first 24 h of ARDS diagnosis:
      influence on outcome.
AB  - BACKGROUND: Airway colonization and infection are frequent complications during
      the course of ARDS. The impact on outcomes of microbiological patterns recovered
      within the first 24 h after diagnosis has not been evaluated. OBJECTIVES: To
      describe the incidence and patterns of bronchial colonization and lung infection
      within the first 24 h of ARDS diagnosis and to evaluate the influence on ICU
      outcomes. METHODS: Prospective study of ARDS patients evaluated within 24 h of
      diagnosis. Patients were studied with tracheobronchial aspirate and right and
      left bronchoscopic protected specimen brush. All samples were cultured
      quantitatively. RESULTS: Fifty-five consecutive patients were included. Twelve
      patients (22%) were clinically suspected of having nosocomial pneumonia (NP),
      which was confirmed microbiologically in 7 patients, a frequency of 13%. In those
      patients without suspected pneumonia, we also found potentially pathogenic
      microorganisms (PPMs) and potentially drug-resistant microorganisms (PDRMs) in
      36% and 31%, respectively. Mortality was not significantly higher in those
      patients with recovery of a PPM (87% vs 73%, p = 0.31), PDRM (89% vs 74%, p =
      0.18), or with NP (79% vs 85%, p = 1.0). CONCLUSION: There is a strikingly high
      rate of PPM recovery in early ARDS. However, neither isolation of pathogenic
      microorganisms nor the confirmation of NP could be associated with an increased
      mortality.

PMID- 16002947
TI  - Quality of dying in the ICU: ratings by family members.
AB  - STUDY OBJECTIVES: To explore the quality of the dying experience and associations
      to higher quality ratings for people who died in an ICU. DESIGN: Retrospective
      study using medical record review and surveys of family members with the Quality
      of Dying and Death (QODD) instrument. SETTING: Four ICUs affiliated with a
      university and a Veterans Affairs Medical Center. PARTICIPANTS: Ninety-four
      family members of 38 ICU decedents. MEASUREMENTS AND RESULTS: We explored
      associations between components of the ICU experience and the overall rating of
      the quality of the dying experience. Overall, family members reported that
      symptoms were poorly controlled: pain under control most or all of the time in
      47%, and breathing comfortably most or all of the time in 3% of patients.
      Families expressed a moderate and variable view of the quality of dying resulting
      in an overall ICU QODD score of 60 +/- 14 (on a scale of 0 to 100) [mean +/- SD].
      Higher ICU QODD scores were associated with control of pain (r = 0.42, p =
      0.009), control of events (r = 0.62, p < 0.001), a "preparation for death" aspect
      of the dying experience--feeling at peace with dying (r = 0.69, p < 0.001), and a
      "whole-person concern"--keeping one's dignity and self-respect (r = 0.50, p <
      0.001). CONCLUSIONS: After adjusting for symptom and personal care scores,
      certain whole-person and preparation-for-death aspects of the dying process, and
      not aggressiveness of end-of-life care, remained the most associated to quality
      ratings. While future research should explore the important predictors of quality
      of dying in the ICU, this study suggests that care at the end of life in the ICU
      include not only managing pain, but also supporting dignity, respect, and peace,
      and maximizing patient control.

PMID- 16002948
TI  - Utility of B-type natriuretic peptide and N-terminal pro B-type natriuretic
      peptide in evaluation of respiratory failure in critically ill patients.
AB  - STUDY OBJECTIVES: B-type natriuretic peptide (BNP) and N-terminal pro BNP
      (NTproBNP) have been shown to correlate with pulmonary arterial wedge pressure
      (PAWP) in patients with heart failure. We studied whether BNP and/or NTproBNP can
      differentiate high- vs low-PAWP respiratory failure in ICU patients. We also
      evaluated if BNP and NTproBNP will reflect accurately cardiac dysfunction and
      predict 30-day survival. DESIGN: Prospective observational study of ICU patients
      in an urban teaching hospital. PATIENTS: Forty-one consecutive patients with
      hypoxic respiratory failure undergoing pulmonary artery catheterization were
      enrolled between January and December, 2003. INTERVENTIONS: BNP and NTproBNP were
      assayed from a venous blood sample. Hemodynamic variables were obtained at the
      time blood was drawn. Survival was documented at day 30. MEASUREMENTS AND
      RESULTS: BNP and NTproBNP correlated significantly with each other (r = 0.656, p
      < 0.001) and inversely with hemodynamic markers of contractility: BNP with
      cardiac index (CI) [r = - 0.481, p < 0.02], and left ventricular stroke work
      index (LVSWI) [r = - 0.384, p < 0.02]; NTproBNP with CI (r = - 0.441, p < 0.02)
      and LVSWI (r = - 0.623, p < 0.001). BNP and NTproBNP did not correlate with PAWP.
      We created receiver operating characteristic (ROC) curves for detection of
      contractile dysfunction using different LVSWI cutoffs. Area under the ROC (AUROC)
      values were larger and more consistent for NTproBNP than for BNP. For LVSWI < 35
      g.m/m(2): BNP AUROC = 0.643, NTproBNP AUROC = 0.885 (p < 0.02); for LVSWI < 30
      g.m/m(2): BNP AUROC = 0.754 (p < 0.02) and NTproBNP AUROC = 0.884 (p < 0.001).
      Mean (+/- SE) concentrations did not differ between the survivors and non
      survivors: BNP, 909.3 +/- 264.2 pg/mL vs 840.9 +/- 171.2 pg/mL; NTproBNP,
      11,630.6 +/- 3,181.8 pg/mL vs 11,777.6 +/- 2,989.9 pg/mL, respectively.
      CONCLUSIONS: NTproBNP and BNP failed to differentiate high- vs low-PAWP
      respiratory failure but were inversely correlated with indexes of cardiac
      contractility. With higher accuracy, NTproBNP may be a more discerning marker
      than BNP in patients with milder cardiac dysfunction. Neither peptide predicted
      short-term mortality.

PMID- 16002949
TI  - Left ventricular apical ballooning due to severe physical stress in patients
      admitted to the medical ICU.
AB  - PURPOSES: We sought to assess the frequency and clinical implications of left
      ventricular apical ballooning (LVAB) in patients who had been admitted to the
      medical ICU for noncardiac physical illnesses. METHODS: Ninety-two consecutive
      patients who were admitted to the medical ICU from March to May 2003 were
      prospectively enrolled. Patients underwent echocardiography on the day of ICU
      admission, and on the third and seventh days in the hospital. LVAB was defined as
      symmetric severe hypokinesia or akinesia of the left ventricular wall, except for
      the basal part of the left ventricle, with a < 50% ejection fraction. RESULTS: Of
      the 92 patients, 65 (71%) were men, and they had a mean (+/- SD) age of 63 +/- 11
      years. LVAB was observed in 26 patients (28%), with a mean lowest ejection
      fraction of 33 +/- 8% (range, 19 to 46%). Compared with the 66 patients (72%)
      without LVAB, those with LVAB had a higher frequency of sepsis (62% vs 14%,
      respectively; p < 0.001), a higher prevalence of hypotension on ICU admission,
      more frequent use of inotropic agents, and a higher frequency of cardiomegaly and
      pulmonary edema (p < 0.005 for each). Sepsis was the only variable associated
      with the development of LVAB (odds ratio, 9.2; 95% confidence interval, 2.4 to
      35.8; p < 0.001). The development of Q-wave or ST-segment displacement was
      associated with LVAB, but the sensitivities were 12% and 19%, respectively. Serum
      creatine kinase level was elevated in 12 of 26 patients (46%) with LVAB. The
      normalization of this condition occurred in 20 of 26 patients (77%) a mean
      duration of 7.4 +/- 5.6 days later (range, 2 to 25 days). The mean 2-month
      survival rate was lower in patients with LVAB than in those without (71 +/- 6% vs
      52 +/- 10%, respectively; p = 0.047). CONCLUSION: LVAB develops in a considerable
      number of patients who are admitted to the medical ICU, and echocardiography is
      useful in detecting this phenomenon.

PMID- 16002950
TI  - Concomitant assessment of depth of sedation by changes in bispectral index and
      changes in autonomic variables (heart rate and/or BP) in pediatric critically ill
      patients receiving neuromuscular blockade.
AB  - OBJECTIVE: We evaluated whether or not changes in bispectral index (BIS) are
      associated with concomitant changes in autonomic variables that are in agreement
      with the different level of sedation that the changes in BIS indicate. DESIGN: A
      retrospective chart review. SETTING: A pediatric ICU of a children's hospital.
      METHODS AND MAIN RESULTS: Charts of patients who were receiving mechanical
      ventilation and IV sedation, neuromuscular blockade, and continuous BIS
      monitoring were enrolled in the study. Changes in BIS values > or = 30% from
      previous readings were evaluated to determine whether or not concomitant changes
      of > or = 10% in autonomic variables, in the same direction, coexisted. Forty
      seven patients (35 male and 12 female) were enrolled in our study; ages ranged
      from 10 days to 18 years (mean, 4.2 +/- 6.2 years [+/- SD]). Twenty-five patients
      were < 1 year of age (53%). All patients were sedated and pharmacologically
      paralyzed. Overall, 387 BIS readings (15%) showed a > or = 30% change from the
      previously documented BIS number. These BIS changes were in agreement with heart
      rate (HR) changes, mean arterial pressure (MAP) changes, and both HR and MAP
      changes in 10.6%, 23.8%, and 5.7% of the time, respectively. The same analysis of
      agreement was done for patients < or = 1 year old, and results were no different
      from those of older patients. Among 21 patients who were not receiving any
      vasoactive drugs (alpha- and/or beta-adrenergic agonists) during the study
      period, 157 BIS recordings (15%) showed a > or = 30% change from the previously
      documented BIS number. The percents of agreement with HR, MAP, and HR and MAP for
      these patients were 14.6%, 17.2%, and 7.6%, respectively. In 26 patients who were
      receiving vasoactive medications during the study, 230 BIS recordings (15%)
      showed a > or = 30% change from the previously documented BIS number. For these
      patients, the percentages of agreement were 7.8%, 28.3%, and 4.3%, respectively.
      Agreement with MAP was significantly better than with HR for this group of
      patients (p < 0.05; Fisher Exact Test). SUMMARY: While significant changes in BIS
      are thought to reflect significant changes in depth of sedation, they have a very
      low rate of agreement with changes in vital signs. In the absence of BIS, the
      level of sedation of chemically paralyzed pediatric patients can be better guided
      by changes in MAP than in HR, particularly in patients receiving vasoactive drug
      treatment.

PMID- 16002951
TI  - Small tumor size and limited smoking history predicts activated epidermal growth
      factor receptor in early-stage non-small cell lung cancer.
AB  - STUDY OBJECTIVE: Epidermal growth factor receptor (EGFR) signaling has been
      implicated in the pathogenesis of bronchial dysplasia and overt non-small cell
      lung cancer (NSCLC). We hypothesized that assaying for EGFR activity using an
      antibody that recognizes phosphorylated EGFR (pEGFR) may identify a subset of
      patients whose tumor cells are dependent on EGFR signaling. We also hypothesized
      that EGFR activity may be prognostic for early-stage NSCLC. DESIGN: We
      constructed high-density tissue microarrays using tissues from 193 surgically
      resected stage I NSCLCs. These arrays were immunostained with a pEGFR antibody,
      and the intensity of staining was correlated with clinicopathologic variables, as
      well as disease-free and overall survival (OS). Staining was scored by intensity
      and the percentage of positively stained tumor cells in triplicate. MEASUREMENTS
      AND RESULTS: We found the expression of pEGFR (with > 50% of tumor cells staining
      positive) in 51% of tumor tissues. We found an inverse correlation between pEGFR,
      and both tumor size and the degree of tobacco smoking. In addition, we found a
      trend in which pEGFR expression was inversely correlated with disease stage (IA
      higher than IB). There was no correlation with sex, histology, or disease-free or
      OS. CONCLUSIONS: Our results suggest that pEGFR levels are present in early-stage
      NSCLC, especially in patients with small tumors and in those with short smoking
      histories, but there is no prognostic impact on a patient's disease course.
      Targeting EGFR may therefore have more promise in chemoprevention or in patients
      with smaller early-stage NSCLCs compared with those with more advanced disease.

PMID- 16002952
TI  - Female sex and bronchioloalveolar pathologic subtype predict EGFR mutations in
      non-small cell lung cancer.
AB  - STUDY OBJECTIVES: The prevalence of epidermal growth factor receptor (EGFR)
      mutations in gefitinib-naive lung cancer patients is higher in adenocarcinomas,
      in women, and in Japanese. To further investigate the prevalence of EGFR
      mutations in relation to ethnic and geographic factors, we evaluated EGFR
      mutations in a series of Taiwanese patients with primary lung adenocarcinomas who
      had never been treated with gefitinib. DESIGN AND METHODS: We retrospectively
      studied 35 primary lung adenocarcinoma samples for mutations in the tyrosine
      kinase domain of EGFR; exons 18, 19, and 21 were analyzed by nested polymerase
      chain reaction and automated sequencing. Clinicopathologic information was
      obtained from patient records and pathology reports. Correlation between EGFR
      mutations and patient characteristics, including sex, smoking history, and
      pathologic subtypes, were evaluated by using the chi(2) test and logistic
      regression analysis. RESULTS: Heterozygous EGFR mutations were detected in 17 of
      35 patients (48%). Missense mutations in exon 21 (13 of 17 patients, 76%) were
      the most frequent mutations detected. EGFR mutations were more frequent in women
      (13 of 18 patients [72%]) than in men (4 of 17 patients [23%]; p = 0.004), more
      frequent in nonsmokers (14 of 21 patients [66%]) than in current smokers (3 of 14
      patients [21%]; p = 0.009), and when any degree of bronchioloalveolar carcinoma
      (BAC) was present (14 of 21 patients [66%]) compared with pure adenocarcinoma (3
      of 14 patients [21%]; p = 0.009). Logistic regression analysis demonstrated that
      female gender (odds ratio [OR], 10.913; 95% confidence interval [CI], 1.778 to
      66.97; p = 0.01) and BAC, including adenocarcinomas with any bronchioloalveolar
      features (OR, 9.708; 95% CI, 1.464 to 64.393; p = 0.019), were significantly
      associated with EGFR mutations. CONCLUSIONS: In our series, female sex and
      bronchioloalveolar pathologic subtype predicted the presence of EGFR mutations in
      lung adenocarcinomas, and the high frequency of EGFR mutations supports the
      hypothesis that genetic backgrounds and/or environmental factors may affect the
      pathogenesis of certain lung cancers.

PMID- 16002953
TI  - Effect of Mycoplasma pneumoniae lysate on interleukin-8 gene expression in human
      respiratory epithelial cells.
AB  - STUDY OBJECTIVES: Mycoplasma pneumoniae is a common cause of lower respiratory
      disease. Several studies have suggested that respiratory infection by M
      pneumoniae is associated with reactive airway disease and asthma. Interleukin
      (IL)-8 has been suggested to have a role in the pathogenesis of the allergic
      inflammation of bronchial asthma, and is well known to be expressed in bronchial
      epithelial cells. MEASUREMENTS: An examination was carried out into the effect of
      M pneumoniae lysate (MPL) and the role of mitogen-activated protein kinases
      (MAPKs) and extracellular signal-regulated kinase (ERK) on IL-8 expression in
      human lung epithelial cells. A549 cells were seeded at a density of 5 x 10(4)
      cells per well and incubated in basal medium for a further 24 h. IL-8 levels were
      determined by an enzyme-linked immunosorbent assay. MAPK phosphorylation was
      assessed by Western blotting. RESULTS: In A549 cells, MPL induced IL-8 release in
      a time- and dose-dependent manner. Pretreatment with PD 98059, which blocks the
      activation of MAPK/ERK kinase 1, inhibited MPL-induced IL-8 production by 64.4%
      at 25 micromol/L. Stimulation of A549 cells by MPL also caused an increase in the
      activity of ERK, compared with the nonstimulated cells. The MPL stimulation had
      no effect on the activities of p38. CONCLUSION: These observations suggest that
      activation of ERK by MPL may be one of the mechanisms that result in an increase
      of the production of IL-8.

PMID- 16002954
TI  - Effects of various body temperatures after lipopolysaccharide-induced lung injury
      in rats.
AB  - STUDY OBJECTIVES: In this study, we determined the effects of various body
      temperatures (BTs) after initiation of lipopolysaccharide (LPS)-induced lung
      injury. DESIGN AND SETTING: Forty-nine, adult, male, Sprague-Dawley rats each
      weighing 300 to 400 g were used METHODS: The treated rats were challenged with
      intraperitoneal (IP) administration of 5 mg/kg LPS. Control animals received IP
      saline solution injections. After 16 h, treated and control animals were
      anesthetized. The animals received direct intratracheal (IT) injection of LPS (1
      mg/0.2 mL) or saline solution (control animals). A cooling or heating blanket was
      then used to control BT. The rats were randomly assigned to three control groups
      of mild hypothermia (34 degrees C) plus saline solution, normothermia (37 degrees
      C) plus saline solution, and mild hyperthermia (39 degrees C) plus saline
      solution, and three LPS groups of mild hypothermia plus LPS, normothermia plus
      LPS, and mild hyperthermia plus LPS, where each condition was maintained for 5 h.
      The mean arterial pressure (MAP) and blood gas concentrations were measured. BAL
      was done in the left lung 5 h after the IT injection of LPS with temperature
      control. Parts of the right lung were excised for myeloperoxidase (MPO) and
      malondialdehyde (MDA) measurements, whereas the rest was collected for wet/dry
      (W/D) ratio determination. RESULTS: Normothermia plus LPS caused significantly
      increased W/D ratio, LDH activities, protein concentrations, and tumor necrosis
      factor-alpha concentrations in BAL fluid, and MPO activities and MDA levels in
      lung tissues when compared to saline solution control group. MAP and Pao(2) were
      significantly decreased. The pathologic picture also showed increased neutrophil
      infiltration in lung tissues. In contrast, treatment with mild hypothermia but
      not hyperthermia significantly attenuated these parameters when compared with the
      normothermia-plus-LPS group. CONCLUSIONS: These experimental data suggest that
      mild hypothermia applied after initiation of acute lung injury induced by LPS in
      rats had a protective effect by inhibiting the inflammatory reaction.

PMID- 16002955
TI  - Aerosolized magnesium sulfate for acute asthma: a systematic review.
AB  - BACKGROUND: The use of MgSO(4) is one of numerous treatment options available
      during exacerbations of asthma. While the efficacy of therapy with IV MgSO(4) has
      been demonstrated, little is known about inhaled MgSO(4). OBJECTIVES: A
      systematic review of the literature was performed to examine the effect of
      inhaled MgSO(4) in the treatment of patients with asthma exacerbations in the
      emergency department. METHODS: Randomized controlled trials were eligible for
      inclusion and were identified from the Cochrane Airways Group "Asthma and Wheez*"
      register, which consists of a combined search of the EMBASE, CENTRAL, MEDLINE,
      and CINAHL databases and the manual searching of 20 key respiratory journals.
      Reference lists of published studies were searched, and a review of the gray
      literature was also performed. Studies were included if patients had been treated
      with nebulized MgSO(4) alone or in combination with beta(2)-agonists and were
      compared to the use of beta(2)-agonists alone or with an inactive control
      substance. Trial selection, data extraction, and methodological quality were
      assessed by two independent reviewers. The results from fixed-effects models are
      presented as standardized mean differences (SMDs) for pulmonary functions and the
      relative risks (RRs) for hospital admission. Both are displayed with their 95%
      confidence intervals (CIs). RESULTS: Six trials involving 296 patients were
      included. There was a non-significant increase [corrected] in pulmonary function
      between patients whose treatments included nebulized MgSO(4) and those whose
      treatments [corrected] did not (SMD, 0.22; 95% CI, -0.02 to 0.47 [corrected] five
      studies); there was also a trend toward reduced [corrected] hospitalizations in
      patients whose treatments included nebulized MgSO(4) (RR, 0.67; 95% CI, 0.41 to
      1.09; four studies). Subgroup analyses demonstrated that lung function
      improvement was similar in adult patients and in those patients who received
      nebulized MgSO(4) in addition to a beta(2)-agonist. CONCLUSIONS: The use of
      nebulized MgSO(4), particularly in addition to a beta(2)-agonist, in the
      treatment of an acute asthma exacerbation appears to produce benefits with
      respect to improved pulmonary function and may reduce the number of hospital
      admissions.

PMID- 16002956
TI  - Cortical substrates for the perception of dyspnea.
AB  - Dyspnea is a common, unpleasant, and impairing symptom in various respiratory
      diseases and other diseases. Despite growing understanding of the multiple
      peripheral mechanisms giving rise to dyspnea, little is known about the cortical
      mechanisms underlying its perception. The results of neuroimaging studies have
      shown that distinct brain areas process the dyspneic sensation, among which the
      anterior insular seems to be the most important. Based on the findings of the
      first relevant neuroimaging studies, this review describes the cortical
      structures associated with the perception of dyspnea. Moreover, similarities to
      the perception of pain are discussed, and implications for future research are
      provided.

PMID- 16002957
TI  - Plethysmographic measurements of specific airway resistance in young children.
AB  - Validated methods for lung function measurements in young children are lacking.
      Plethysmographic measurement of specific airway resistance (sRaw) provides such a
      method applicable from 2 years of age. sRaw gauges airway resistance from the
      measurements of the pressure changes driving the airflow during tidal breathing.
      These measurements require no active cooperation and are therefore feasible in
      children from 2 years of age. The within-observer and between-observer
      variability of sRaw in young children compare favorably with alternative methods.
      Reference values are available for sRaw and have allowed discrimination of young
      children with respiratory disease. Bronchial hyperresponsiveness can be
      determined with acceptable short-term and long-term repeatability and provides
      good discrimination between asthmatics and healthy young children. The effects of
      the major antiasthmatic therapies have also been documented by this technique,
      and sRaw has recently been used in longitudinal studies of young children with
      chronic pulmonary diseases. Future developments should provide improved
      algorithms for thermal correction of the respired volumes and adapt the equipment
      to the special needs of young children. This article reviews the method, and
      proposes a protocol and criteria for quality assurance for assessment of sRaw in
      preschool children from 2 years of age. sRaw measurements offers a method for
      clinical monitoring and research during this critical period of growth and
      development early in life.

PMID- 16002958
TI  - Bypassing the pump: changing practices in coronary artery surgery.
AB  - Improvements in techniques in coronary revascularization over the past decade
      have led to a revival of interest in off-pump coronary artery surgery. A fifth of
      coronary revascularization procedures are now performed off-pump. Randomized
      trials comparing off-pump surgery with conventional coronary artery bypass
      grafting using cardiopulmonary bypass (CPB) mainly included low-risk patients and
      were therefore underpowered to detect a difference in mortality. Current
      evidence, however, suggests a significant reduction in morbidity with off-pump
      surgery. The avoidance of CPB and the elimination of any aortic manipulation may
      significantly reduce the risk of stroke. Those benefits are likely to be most
      marked in older, sicker patients, who represent an increasing proportion of the
      surgical population.

PMID- 16002959
TI  - Lung cancer in women: emerging differences in epidemiology, biology, and therapy.
AB  - Lung cancer is the major cause of cancer-related death in both men and women in
      the United States. Emerging evidence indicates that there are differences in the
      pathogenesis and possibly increased susceptibility to lung cancer in women. In
      addition, considerable data support small, but important differences favoring
      women in terms of response to therapy and long-term survival after the diagnosis
      of lung cancer, regardless of histology or stage. These differences in both
      biology and outcome will be important considerations in the design of future
      trials of screening and therapy for lung cancer.

PMID- 16002960
TI  - Electromagnetic catheter navigation during bronchoscopy: validation of a novel
      method by conventional fluoroscopy.
AB  - BACKGROUND: Electromagnetic navigation in bronchoscopy is a novel method for
      assisting in the localization of peripheral lung lesions. STUDY OBJECTIVE: To
      assess the usability, accuracy, and safety of electromagnetic navigation during
      flexible bronchoscopy in a clinical setting. DESIGN: Prospective evaluation.
      PATIENTS: Consecutive patients referred to the bronchoscopy unit for the
      diagnosis of peripheral infiltrates or solitary pulmonary nodules (SPNs).
      METHODS: Navigation was performed using an electromagnetic tracking system with a
      position sensor encapsulated in the tip of a flexible catheter that was pushed
      through the working channel of the bronchoscope. Real-time, multiplanar
      reconstruction of a previously acquired CT data set provided three-dimensional
      views for localization of the catheter. To match the position of the sensor with
      the CT scan, four anatomic landmarks were used for registration. The sensor
      position generated in the navigation system was controlled by fluoroscopy, and
      the corresponding error distances were measured. This was performed with all SPNs
      and at two different peripheral locations of the right upper lobe (RUL). RESULTS:
      Sixteen patients (10 men and 6 women; mean age, 63.7 years) were studied.
      Navigation prolonged bronchoscopy by 3.9 +/- 1.3 min (mean +/- SD). The
      navigation system identified all lesions. The position sensor achieved a direct
      hit in three of five SPNs. Fluoroscopy failed to recognize three SPNs (60%) and
      three infiltrates (38%). The mean error distances between sensor tip position and
      fluoroscopically verified RUL reference position were 10.4 mm (lateral position)
      and 12.5 mm (apical position) respectively. The mean error distances between the
      sensor tip and two endobronchial registration points at the end of the procedure
      were 4.2 mm and 5.1 mm, respectively. CONCLUSION: Electromagnetic navigation is
      useful, accurate, and safe in the localization of peripheral lung lesions and may
      help to improve the yield of diagnostic bronchoscopic procedures.

PMID- 16002961
TI  - Endobronchial ultrasonography guidance for transbronchial needle aspiration using
      a double-channel bronchoscope.
AB  - STUDY OBJECTIVES: Endobronchial ultrasonography (EBUS) is used as guidance for
      transbronchial needle aspiration (TBNA), and real-time imaging of the needle
      position cannot be confirmed with a single-channel bronchoscope. We assessed the
      usefulness of EBUS-guided TBNA using a double-channel bronchoscope (EBUS-D),
      which provides real-time needle position, and compared it with EBUS-guided TBNA
      using a single-channel bronchoscope (EBUS-S). DESIGN: Randomized, comparative
      prospective study. SETTING: Hiroshima City Hospital, a tertiary-referral teaching
      hospital. PATIENTS: Between January 2000 and August 2003, 55 patients with
      intrathoracic lymphadenopathy were included. Patients were randomized to undergo
      EBUS-D (n = 30) or EBUS-S (n = 25). METHODS: EBUS-D: The EBUS probe and TBNA
      catheter were inserted simultaneously through a double-channel bronchoscope. Once
      the needle placement in the lesion was confirmed by EBUS, TBNA was performed.
      EBUS-S: The EBUS probe was removed after the determination of the penetration
      site. Then, the TBNA catheter was inserted and TBNA was performed. RESULTS: All
      the lymph nodes could be visualized with EBUS in each group of patients. In the
      EBUS-D group, the TBNA needle was visualized as a hyperechoic point on the real
      time EBUS image. The diagnostic accuracy rate of EBUS-D and EBUS-S were
      statistically significantly different (97% vs 76%, respectively; p = 0.025). On
      second attempt of TBNA, the diagnostic rate of the EBUS-D group was superior to
      that of the EBUS-S group (85.7% vs 33.3%, respectively; p = 0.036). The mean
      number of penetrations was 1.24 in the EBUS-D group and 1.36 in the EBUS-S group.
      No complications were observed in the EBUS-D group, but a self-limiting
      hemorrhage occurred in a patient in the EBUS-S group. CONCLUSION: EBUS-D is
      useful for diagnosing intrathoracic lymphadenopathy, and the obtained specimen
      with real-time confirmation of the needle is directly proportional to an accurate
      diagnosis.

PMID- 16002962
TI  - A prospective study of the timing and cost-effectiveness of bronchial washing
      during bronchoscopy for pulmonary malignant tumors.
AB  - STUDY OBJECTIVES: The value of obtaining washings during fiberoptic bronchoscopy
      in the workup of lung cancer is controversial. Moreover, the optimal timing of
      washing relative to biopsy and brushing is not known. In this study, the
      diagnostic yields of washings before and after biopsy and brushings were
      compared. The different diagnostic strategies were assessed in terms of yield and
      costs. DESIGN: A prospective study performed from 2001 to 2003 in a secondary
      care medical center. MEASUREMENTS AND RESULTS: Two hundred twenty-one patients
      underwent flexible bronchoscopy, and the diagnostic yield of washings before
      biopsy and brushing (strategy I) and after biopsy and brushing (strategy II)
      specimens were assessed. Using the known probabilities and costs for various
      bronchoscopic procedures, the expected utility of a number of diagnostic
      strategies was estimated. Patients (147 men and 74 women) were included in the
      study in whom a definite cytologic or histologic diagnosis of pulmonary
      malignancy had been made. The diagnostic yield of strategy I was 72% for visible
      tumors and 36% for nonvisible tumors. For strategy II, the diagnostic yield was
      74% for visible tumors and in 42% for nonvisible tumors. The comparison of
      strategies I and II for both visible and nonvisible tumors revealed that 176
      cases were concordant (80%); in 19 cases (9%) the cytologic analysis of washings
      in strategy I was positive for malignancy and negative in strategy II. In 26
      cases (12%) washings in strategy II were positive and negative in strategy I (p =
      0.37). An analysis of the diagnostic yield of both washings in visible tumors and
      nonvisible tumors showed no significant difference. In 13 patients, a diagnosis
      of malignancy was established only by washings (6%). Confining the laboratory
      investigations of washings or brush samples to those cases in which the initial
      findings of the biopsies are negative (the two-stage procedure) is more cost
      effective than examining all biopsy, brushing, and washing specimens. In patients
      with visible tumors, brushing or washing in addition to biopsy is equally cost
      effective; in patients with nonvisible tumors, biopsy combined with washing is
      the preferred option. CONCLUSIONS: No difference in the diagnostic yield could be
      demonstrated for washings before or after biopsies and brushings. Although the
      additional diagnostic yield of washing and brushing during bronchoscopy is
      relatively low, it is cost-effective to use these procedures in the diagnostic
      workup of patients who are clinically suspected of having a pulmonary malignancy.

PMID- 16002963
TI  - Fellows as teachers: the teacher-assistant experience during pulmonary
      subspecialty training.
AB  - STUDY OBJECTIVES: Physicians undergoing medical subspecialty training, referred
      to as "fellows" in the United States, often serve as small group tutors. There
      are few reports, however, on whether fellows benefit from their experience
      teaching in the classroom. The purpose of this article is to describe the teacher
      assistant requirement for fellows in a pulmonary and critical care training
      program and gain the perspectives of program graduates on their experiences as
      teacher assistants. DESIGN, SETTING, AND PARTICIPANTS: The structure of the
      teacher-assistant requirement is described in detail. We also surveyed 55
      consecutive graduates of our Pulmonary and Critical Care Fellowship program
      located in the United States on the educational value of teaching pathophysiology
      to preclinical medical students. RESULTS: Fellows and one or two faculty members
      co-teach groups of 15 to 25 second-year medical students during 22 h of case
      based conferences over a 6-week period. Weekly meetings for teacher assistants
      foster improved teaching skills and provide insight into the basic tenets of
      structuring and implementing the course. Fellows receive formal and informal
      feedback on their performance. Fifty of 55 graduates (91%) returned the survey.
      Respondents rated the acquisition of teaching skills and knowledge of pulmonary
      pathophysiology as the most useful aspects of their experience. Eighty-seven
      percent rated their overall experience favorably, and 90% agreed that teaching
      the course should remain a curriculum requirement. The responses of physicians in
      academic and community practice were comparable. CONCLUSIONS: Graduates of our
      Pulmonary and Critical Care Fellowship valued their teacher-assistant experience.
      This article may serve as a model for other subspecialty programs that are
      interested in formally incorporating teaching into their training program and may
      provide an impetus for the additional exploration of teacher-assistant
      experiences at other institutions.

PMID- 16002964
TI  - Pro/Con debate: lung allocation should be based on medical urgency and transplant
      survival and not on waiting time.

PMID- 16002965
TI  - Sputum induction and bronchoscopy for assessment of ozone-induced airway
      inflammation in asthma.
AB  - BACKGROUND: Neutrophilic airway inflammation, as defined by cell counts in
      respiratory tract lining fluid (RTLF), is a key end point in many studies of
      respiratory toxicity in both healthy and asthmatic subjects. BAL and sputum
      induction (SI) are the most common methods of sampling RTLF in such studies.
      However, the comparability of these methods (BAL and SI) after experimental
      treatment has not been investigated in a head-to-head controlled trial. METHODS:
      To determine whether BAL and SI are comparable and can be used in place of each
      other in the assessment of neutrophilic airway inflammation after ozone (O(3))
      exposure, we exposed 13 asthmatic subjects to either 0.2 ppm of O(3) or filtered
      air (FA) followed by either BAL or SI. Subjects then underwent the alternate
      (O(3) or FA) exposure followed by the same method of RTLF sampling. Next,
      subjects repeated the same exposure protocol with the alternate method of RTLF
      sampling. Differences in inflammatory indexes including the percentage of
      polymorphonuclear neutrophils (%PMNs) between the exposures were then correlated
      by regression analysis. RESULTS: The %PMNs in sputum was poorly correlated with
      that in BAL fluid (R = 0.12). The correlation between the %PMNs in sputum and in
      the bronchial fraction of BAL (BFx) fluid, however, was somewhat higher (R =
      0.50). Furthermore, the uncertainty of the estimate of %PMN values in BFx fluid
      and BAL fluid based on those of sputum values, using regression models, was
      almost as great as the magnitude of the O(3) effect itself (ie, 9.7% and 5.5%
      estimate errors for O(3) effects of 17.0% and 7.5%, respectively). CONCLUSION: We
      concluded that SI and BAL indexes are not directly interchangeable in the
      assessment of O(3)-induced airway inflammation in asthmatic subjects.

PMID- 16002966
TI  - Inhalational nickel carbonyl poisoning in waste processing workers.
AB  - BACKGROUND: Nickel carbonyl is formed when carbon monoxide comes into contact
      with active nickel. The inhaled nickel carbonyl is rapidly absorbed and
      distributed mainly to the lungs, brain, adrenal glands, and kidneys. In severe
      cases, acute nickel carbonyl exposure has been reported to cause death. DESIGN:
      Descriptive study. PATIENTS: Seven young men presented with fever, chills,
      substernal pleuritic chest pain, and exertional dyspnea. Extensive
      microbiological and toxicological investigations (including blood, urine, and
      bronchial specimens) for known pathogens and occupational toxins were performed.
      The clinical course and radiologic findings of each patient, including autopsy
      findings of three patients who died, were described. RESULTS: Four patients
      received treatment in the ICU. Elevated urinary nickel concentration was detected
      in all patients. Results of extensive microbiological investigations were
      unremarkable. No patients received chelating agents. Pulmonary consolidation,
      edema, hemorrhage, and fibrosis were observed at autopsy in patients who died. An
      out-of-date chemical used during neutralization of nickel waste was implicated as
      the source of nickel carbonyl poisoning. CONCLUSIONS: High mortality was reported
      in patients who presented subacutely following nickel carbonyl exposure. Further
      studies should be performed to clarify the role of chelation therapy in the
      subacute phases following nickel carbonyl exposure.

PMID- 16002967
TI  - Hyperoxia-induced hypocapnia: an underappreciated risk.

PMID- 16002968
TI  - A 63-year-old woman with subcutaneous emphysema following endotracheal
      intubation.

PMID- 16002969
TI  - Paracardiac opacity following inferior- and middle-lobe resection for
      bronchogenic carcinoma: unsuspected diagnosis.
AB  - We report the case of a patient who had benefited initially from a right middle
      and lower lobectomy for bronchogenic carcinoma and who had an extensive
      radiologic workup in an outside hospital in the early postoperative period. Based
      on CT scan findings, this patient was referred back with a diagnosis that conveys
      both medical and medicolegal issues: a gossypiboma (or retained surgical sponge).
      We describe herein the unexpected operative findings that highlight the
      difficulty in accurately diagnosing intrathoracic foreign bodies.

PMID- 16002970
TI  - Peak expiratory flow with or without a brief postinspiratory pause.
AB  - BACKGROUND: The duration of postinspiratory pause prior to forced expiration may
      significantly influence the peak expiratory flow (PEF) measured during maximal
      forceful expirations. In comparison with maneuvers without a postinspiratory
      pause, maneuvers with 4 to 6-s pause at total lung capacity (TLC) result in
      decreased PEF values. The extent to which brief pauses (< 2 s) similarly affect
      PEF values is unknown. METHODS: Thirty-six healthy volunteers (mean [+/-SD] age,
      35 +/- 8 years; 18 men) performed a series of maximal forceful expirations with
      two different types of maneuvers. One maneuver (NP) included no inspiratory pause
      at TLC prior to forceful expiration, whereas the second (P) included a brief
      pause (< or = 2 s). The speed of inhalation to TLC was rapid and similar for both
      maneuvers. The highest PEF for each maneuver was used for analysis. RESULTS: The
      maximal PEF did not differ (p > 0.05) between the P and NP maneuvers (7.78 +/-
      1.45 vs 7.83 +/- 1.45 L/s, respectively). Comparison of the intermaneuver
      differences showed a bias of 0.05 L/s and 95% confidence interval in the range of
      -0.9 to 1.0 L/s. CONCLUSIONS: Forceful expiratory maneuvers with or without
      postinspiratory pauses of < or = 2 s produce identical maximal PEF values and,
      therefore, can be used interchangeably for the spirometric measurement of PEF in
      healthy subjects.

PMID- 16002971
TI  - Alpha1-antitrypsin and neutrophil elastase imbalance and lung cancer risk.
AB  - OBJECTIVE: Imbalance between alpha(1)-antitrypsin and neutrophil elastase is an
      underlying cause of lung tissue damage that may create a favorable host
      environment for carcinogenesis. We conducted a case-control study to investigate
      whether genetic variations indicative of alpha(1)-antitrypsin deficiency (A1ATD)
      or an excess of neutrophil elastase modify lung cancer risk DESIGN: The case
      patients were 305 consecutively identified primary lung cancer patients, and the
      control subjects were 338 community residents. Protease inhibitor-1 (PI1),
      encoding alpha(1)-antitrypsin, was typed by an isoelectric focusing assay.
      Neutrophil elastase-2 (ELA2), encoding neutrophil elastase, was typed by two
      single-nucleotide polymorphism sites. Multivariable logistic regression models
      tested the independent and interactive effects of PI1, ELA2, tobacco smoke
      exposure, COPD, and family history of lung cancer RESULTS: Sex and ethnicity were
      comparable between case patients and control subjects, but case patients were
      more likely to be smokers, and to have a history of COPD, environmental tobacco
      smoke exposure, and a positive family history of lung cancer. Haplotype analysis
      indicated an overall strong association between the two ELA2 markers and lung
      cancer risk. Our best-fitting model showed significant and independent effects of
      the PI1-deficient allele (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4
      to 3.0) and the ELA2 T-G haplotype (OR, 4.1; 95% CI, 1.9 to 8.9) on lung cancer
      risk, and an increased risk (OR, 2.6; 95% CI, 2.4 to 2.8) for individuals
      carrying both a PI1-deficient allele and a G-G haplotype CONCLUSIONS: Genotypes
      indicative of A1ATD and/or an excess of neutrophil elastase are significantly
      associated with lung cancer risk. Our findings may provide opportunities to
      better understand the mechanisms of lung cancer development and risk reduction.

PMID- 16002972
TI  - Clinical features of 5,628 primary lung cancer patients: experience at Mayo
      Clinic from 1997 to 2003.
AB  - STUDY OBJECTIVES: To improve the current understanding of the etiology and
      natural history of primary lung cancer, we need to study the dynamic changes of
      clinical presentation and prognosis among a large number of patients with newly
      diagnosed lung cancer. In this report, we present the clinical features and
      survival rates up to 5 years of a patient cohort. DESIGN: We identified 5,628
      primary lung cancer patients between 1997 and 2002 and followed them through 2003
      using multiple, complementary resources. MEASUREMENTS AND RESULTS: Of the 5,628
      patients, 58% were men with a mean age at lung cancer diagnosis of 66 years, and
      42% were women with a mean age at diagnosis of 64 years. Ten percent were < 50
      years, and 8% were > 80 years at diagnosis. A tobacco smoking history was present
      in 89% of patients, and 40% were smoking at the time of diagnosis. The estimated
      overall 5-year survival rates of patients with non-small cell lung cancer (NSCLC)
      by disease stage was as follows: IA, 66%; IB, 53%; IIA, 42%; IIB, 36%; IIIA, 10%;
      IIIB, 12%; and IV, 4%. The 5-year survival rate of patients with small cell lung
      cancer was 22% for limited disease and 1% for extensive disease. Approximately
      50% of all patients are participants in one or more research studies, and nearly
      75% of these patients have donated biological specimens for research. CONCLUSION:
      The survival rate of this cohort of lung cancer patients was slightly improved
      compared with earlier reports, particularly for patients with low-stage NSCLC.
      Our patient and biospecimen resource has enabled us to obtain timely results from
      clinical and translational research of lung cancer.

PMID- 16002973
TI  - Necessity of 2-night polysomnographic study in children with sleep-related
      disordered breathing.

PMID- 16002974
TI  - Interleukin-8 neutralization for COPD.

PMID- 16002975
TI  - Striving for excellent end-of-life care.

PMID- 16002976
TI  - Prediction of pulmonary artery pressure.

PMID- 16002978
TI  - Vascular endothelial growth factor levels in pleural fluid and serum of patients
      with tuberculous pleural effusions.

PMID- 16002979
TI  - At least three FEV1 blows are required at each time point during the assessment
      of bronchial hyperresponsiveness.

PMID- 16002980
TI  - Transfusion-related acute lung injury, acute lung injury, and ARDS: close
      relatives.

PMID- 16002981
TI  - Low-molecular-weight heparin and outcomes.

PMID- 16002982
TI  - Testing lung function decline to time lung transplantation.

PMID- 16002983
TI  - Value of fiberoptic bronchoscopy in patients undergoing surgery for solitary
      pulmonary nodules.

PMID- 16002984
TI  - Clopidogrel as antithrombotic therapy in atrial fibrillation.

PMID- 16002985
TI  - Electronic data sources for kinetic models of cell signaling.
AB  - Functional understanding of signaling pathways requires detailed information
      about the constituent molecules and their interactions. Simulations of signaling
      pathways therefore build upon a great deal of data from various sources. We first
      survey electronic data resources for cell signaling modeling and then based on
      the type of data representation the data sources are broadly classified into five
      groups. None of the data sources surveyed provide all required data in a ready-to
      be-modeled fashion. We then put forward a "wish list" for the desired attributes
      for an ideal modeling centric database. Finally, we close with perspectives on
      how electronic data sources for cell signaling modeling have developed. We
      suggest that future directions in such data sources are largely model-driven and
      are hinged on interoperability of data sources.

PMID- 16002986
TI  - Dynamic characteristics of transient responses.
AB  - Transient responses of signaling molecules are seen in a wide variety of cellular
      processes that are mediated by distinct molecular mechanisms. Although transient
      responses might intuitively be thought to depend on the absolute concentration of
      growth factors or the intensity of stimulation, we here introduce that some
      transient responses are prompted by temporal rate of increase of stimulation,
      rather than intensity of stimulation, by three independent mechanisms. These
      include the Ras system with fast activation and slow inactivation, the ERK
      dependent negative feedback loop system, and the receptor degradation system, all
      of which can be commonly seen in various signaling networks. In addition, we show
      the distinct transient and steady state characteristics of these systems.

PMID- 16002987
TI  - Reproductive/urogenital organ development and molecular genetic cascades:
      glamorous developmental processes of bodies.
AB  - At the beginning of the 21st century, developmental biologists together with
      medical researchers in a wide range of fields are witnessing rapid progress in
      molecular developmental biology. For example, conditional gene knockout systems
      are being designed to tackle questions about organogenesis and body plan
      formation in experimental mouse models and experimental designs include several
      compound mutant analyses and genome modification strategies. On the other hand,
      several fields remain relatively unexplored. Molecular mechanisms of sex
      differentiation are one of the unexplored huge area. Unanswered questions include
      the molecular genetic cascade of gonad formation, reproductive organ formation,
      uterus, external genitalia and mammary gland formation, and also the molecular
      mechanisms of signal transduction, and gene regulation by nuclear hormone
      receptors. This special thematic review series entitled, "Reproductive/urogenital
      organ development and molecular genetic cascades: glamorous developmental
      processes of bodies," covers such a wide range of topics. For this special issue,
      I have asked active researchers to contribute reviews of these topics which I
      believe will be useful not only for molecular developmental biologists, but also
      for researchers in biochemistry and cell biology. It will be my great pleasure if
      this special thematic issue encourages scientists to study this exciting research
      field.

PMID- 16002988
TI  - Genitourinary functions of Hoxa13 and Hoxd13.
AB  - In the United States, Japan, United Kingdom, and Sweden, birth defects affecting
      the growth and development of the genitourinary (GU) regions are becoming
      increasingly prevalent, with incidences ranging as high as 1 in 125 live births.
      To understand the basis for these malformations, scientists have begun to examine
      the function of developmental genes in GU tissues. At the forefront of these
      investigations are studies examining the role of the 5' HOX proteins during the
      formation of the GU region. In this report we discuss what is known about HOXA13
      and HOXD13 function during GU development, highlighting some of the cellular and
      molecular mechanisms controlled by these proteins during the GU formation.
      Finally, the translational benefits of identifying HOX target genes are
      discussed; first to explain the prevalence of some GU defects as well as a
      mechanism to facilitate their prevention in the birth population.

PMID- 16002989
TI  - Development of the mammalian female reproductive tract.
AB  - The female reproductive tract (FRT), which includes the oviduct, uterus, cervix
      and vagina, is critical for mammalian reproduction. Recent research using
      knockout mice has contributed substantially to our understanding of the molecular
      mechanisms governing FRT development. Aside from satisfying our curiosities about
      the origin of life, these studies have provided us with a better understanding of
      FRT disorders and ways to improve female fertility. Here we review genes that are
      involved in various stages of sexual duct formation and development in mammals.
      In addition, the effect of exogenous estrogen such as DES on FRT development is
      also discussed.

PMID- 16002990
TI  - Cleavage at the carboxyl-terminus of Ku80 during apoptosis in human Jurkat T
      cells.
AB  - We have previously reported that the amount of Apg-2, an Hsp110 family protein,
      decreases during apoptosis in Jurkat T cells. Since we hypothesized that Apg-2
      would be cleaved by caspase-3 during apoptosis, a cleavage-site-directed antibody
      was raised against the carboxyl-terminus of the Apg-2 fragment that appears after
      the cleavage by caspase-3. Although this antibody could not detect the Apg-2
      fragment in apoptotic cells, three additional fragments were unexpectedly
      detected. Based on the results of microsequencing, one of these fragments was
      identified as Ku80. Ku80 is a nuclear protein and a component of DNA-dependent
      protein kinase (DNA-PK). In this study, we observed that Ku80 is cleaved at Asp
      730 residue during apoptosis, and this cleavage occurs in the nucleus in the
      early apoptotic phase. Furthermore, Ku80 is distributed in the cytoplasm of
      nuclear fragmented apoptotic cells, although the cleaved fragment contains the
      nuclear-localization signal (NLS). Our study clearly shows that Ku80 is cleaved
      in the nucleus, and distributes in the cytoplasm during apoptosis.

PMID- 16002991
TI  - Protein transduction assisted by polyethylenimine-cationized carrier proteins.
AB  - Previously, we have reported that cationized-proteins covalently modified with
      polyethylenimine (PEI) (direct PEI-cationization) efficiently enter cells and
      function in the cytosol [Futami et al. (2005) J. Biosci. Bioeng. 99, 95-103].
      However, it may be more convenient if a protein could be delivered into cells
      just by mixing the protein with a PEI-cationized carrier protein having a
      specific affinity (indirect PEI-cationization). Thus, we prepared PEI-cationized
      avidin (PEI-avidin), streptavidin (PEI-streptavidin), and protein G (PEI-protein
      G), and examined whether they could deliver biotinylated proteins and antibodies
      into living cells. PEI-avidin (and/or PEI-streptavidin) carried biotinylated GFPs
      into various mammalian cells very efficiently. A GFP variant containing a nuclear
      localization signal was found to arrive even in the nucleus. The addition of a
      biotinylated RNase A derivative mixed with PEI-streptavidin to a culture medium
      of 3T3-SV-40 cells resulted in remarkable cell growth inhibition, suggesting that
      the biotinylated RNase A derivative entered cells and digested intracellular RNA
      molecules. Furthermore, the addition of a fluorescein-labeled anti-S100C (beta
      actin binding protein) antibody mixed with PEI-protein G to human fibroblasts
      resulted in the appearance of a fluorescence image of actin-like filamentous
      structures in the cells. These results indicate that indirect PEI-cationization
      using non-covalent interaction is as effective as the direct PEI-cationization
      for the transduction of proteins into living cells and for expression of their
      functions in the cytosol. Thus, PEI-cationized proteins having a specific
      affinity for certain molecules such as PEI-streptavidin, PEI-avidin and PEI
      protein G are concluded to be widely applicable protein transduction carrier
      molecules.

PMID- 16002992
TI  - Analysis of human UDP-glucose dehydrogenase gene promoter: identification of an
      Sp1 binding site crucial for the expression of the large transcript.
AB  - UDP-glucose dehydrogenase (UGDH) catalyzes the conversion of UDP-glucose to UDP
      glucuronic acid, which is required in liver for the excretion of toxic compounds,
      and for the biosynthesis of complex carbohydrates, such as hyaluronan, in many
      cell types. Analysis of a human EST database, as well as the results of a 5'-RACE
      experiment, have revealed the presence of two transcription start sites
      approximately 160 bp apart in the human UGDH gene confirming previous Northern
      hybridization results. To delineate the regions in the UGDH promoter required for
      regulating the expression of the gene, in particular the synthesis of the large
      transcript, serial deletions of the 2.1-kb UGDH promoter region were constructed
      and their activities determined by the firefly luciferase reporter gene assay.
      Our results indicate that the region from nucleotide position -486 to -632
      relative to the start of the small transcript contains positive regulatory
      elements that contribute to gene expression. Mithramycin A, an inhibitor of
      transcription factor Sp1, abrogates the promoter activity, suggesting the
      involvement of this specific protein in UGDH expression. By using site-directed
      mutagenesis, we analyzed the functional contribution of three putative Sp1
      binding elements within this region. A mutation at position -564 demonstrated
      that this site serves as an enhancing element in both HepG2 and HeLa cells. The
      complex formation pattern revealed by an electrophoretic mobility shift assay as
      well as an anti-Sp1 antibody-mediated supershift assay confirmed the identity of
      this GC box as an Sp1 binding motif. Our results thus identify an alternative
      transcription start site on the UGDH promoter, and locate the cis-element that
      greatly enhances the basal transcriptional activity of UGDH gene.

PMID- 16002993
TI  - Selective inhibition of Fcepsilon RI-mediated mast cell activation by a truncated
      variant of Cbl-b related to the rat model of type 1 diabetes mellitus.
AB  - Ubiquitin-protein ligase Cbl-b negatively regulates high affinity IgE receptor
      (FcepsilonRI)-mediated degranulation and cytokine gene transcription in mast
      cells. In this study, we have examined the role of a truncated variant of Cbl-b
      related to the rat model of type 1 diabetes mellitus using the mast cell
      signaling model. Overexpression of the truncated Cbl-b that lacks the C-terminal
      region did not suppress the activation of proximal and distal signaling molecules
      leading to degranulation. FcepsilonRI-mediated tyrosine phosphorylation of Syk,
      Gab2, and phospholipase C-gamma1, and activation of c-Jun N-terminal kinase
      (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein
      kinase (MAP kinase), and inhibitor of nuclear factor kappaB kinase (IKK), and
      generation of Rac1 are unaffected in cells overexpressing the truncated Cbl-b in
      the lipid raft. On the other hand, FcepsilonRI-mediated transcriptional
      activation of nuclear factor of activated T cells (NFAT), and transcription of
      interleukin-3 (IL-3) and IL-4 mRNA are inhibited by overexpression of the
      truncated variant of Cbl-b. This suppression parallels the re
      compartmentalization of specific effector molecules in the lipid raft. These
      structural and functional analyses reveal the mechanism underlying the selective
      inhibition of cellular signaling by the truncated variant of Cbl-b related to
      insulin-dependent diabetes mellitus.

PMID- 16002994
TI  - Design, expression and solid-state NMR characterization of silk-like materials
      constructed from sequences of spider silk, Samia cynthia ricini and Bombyx mori
      silk fibroins.
AB  - Silk has a long history of use in medicine as sutures. To address the
      requirements of a mechanically robust and biocompatible material, basic research
      to clarify the role of repeated sequences in silk fibroin in its structures and
      properties seems important as well as the development of a processing technique
      suitable for the preparation of fibers with excellent mechanical properties. In
      this study, three silk-like protein analogs were constructed from two regions
      selected from among the crystalline region of Bombyx mori silk fibroin,
      (GAGSGA)(2), the crystalline region of Samia cynthia ricini silk fibroin,
      (Ala)(12), the crystalline region of spider dragline silk fibroin, (Ala)(6), and
      the Gly-rich region of spider silk fibroin, (GGA)(4). The silk-like protein
      analog constructed from the crystalline regions of the spider dragline silk and
      B. mori silk fibroins, (A(6)SCS)(8), that constructed from the crystalline
      regions of the S. c.ricini and B. mori silk fibroins, (A(12)SGS)(4), that
      constructed from and the crystalline region of S. c.ricini silk fibroin and the
      glycine-rich region of spider dragline silk fibroin, (A(12)SGS)(4),were expressed
      their molecular weights being about 36.0 kDa, 17.0 kDa and 17.5 kDa, respectively
      in E. coli by means of genetic engineering technologies. (A(12)SCS)(4) and
      (A(12)SGS)(4 )undergo a structural transition from alpha-helix to beta-sheet on a
      change in the solvent treatment from trifluoroacetic acid (TFA) to formic acid
      (FA). However, (A(6)SCS)(8) takes on the beta-sheet structure predominantly on
      TFA treatment and FA treatment. Structural analysis was performed on model
      peptides selected from spider dragline and S. c.ricini silks by means of (13)C
      CP/MAS NMR.

PMID- 16002995
TI  - Overexpression of RasN17 fails to neutralize endogenous Ras in MCF7 breast cancer
      cells.
AB  - Receptor tyrosine kinases of the ErbB family have been implicated in the
      onset/progression of a number of neoplasias. In these diseases, ErbB receptor
      expression may be accompanied by constitutive activation caused by molecular
      alterations, overexpression, or ligand binding. An important signaling route
      activated by these receptors that has been linked to the stimulation of cell
      proliferation is the Ras route. Here we have investigated the action of a mutant
      Ras form, H-RasN17, on the proliferation of the breast cancer epithelial cell
      line MCF7 cells. In these cells expression of RasN17 failed to affect serum or
      ErbB receptor-stimulated proliferation. Analysis of the action of RasN17
      indicated that overexpression of this mutant form of Ras did not affect
      neuregulin or protein kinase C-induced activation of Erk1/2. In addition, RasN17
      failed to prevent activation of endogenous N-Ras and H-Ras even though the levels
      of the latter were much lower than those of the RasN17 form. The failure of
      RasN17 to prevent endogenous Ras activation did not appear to be due to deficient
      processing or sorting of the mutated form. These data indicated that the action
      of RasN17 as a bona fide inhibitor of Ras depends on the cell type and requires
      detailed analysis of the biochemical and biological properties of RasN17,
      particularly with respect to the activation of endogenous Ras.

PMID- 16002996
TI  - Biochemical and functional characterization of BLUF-type flavin-binding proteins
      of two species of cyanobacteria.
AB  - BLUF (a sensor of Blue-Light Using FAD) is a novel putative photoreceptor domain
      that is found in many bacteria and some eukaryotic algae. As found on genome
      analysis, certain cyanobacteria have BLUF proteins with a short C-terminal
      extension. As typical examples, Tll0078 from thermophilic Thermosynechococcus
      elongatus BP-1 and Slr1694 from mesophilic Synechocystis sp. PCC 6803 were
      comparatively studied. FAD of both proteins was hardly reduced by exogenous
      reductants or mediators except methylviologen but showed a typical spectral shift
      to a longer wavelength upon excitation with blue light. In particular, freshly
      prepared Tll0078 protein showed slow but reversible aggregation, indicative of
      light-induced conformational changes in the protein structure. Tll0078 is far
      more stable as to heat treatment than Slr1694, as judged from flavin
      fluorescence. The slr1694-disruptant showed phototactic motility away from the
      light source (negative phototaxis), while the wild type Synechocystis showed
      positive phototaxis toward the source. Yeast two-hybrid screening with slr1694
      showed self-interaction of Slr1694 (PixD) with itself and interaction with a
      novel PatA-like response regulator, Slr1693 (PixE). These results were discussed
      in relation to the signaling mechanism of the "short" BLUF proteins in the
      regulation of cyanobacterial phototaxis.

PMID- 16002997
TI  - Effects of repeated antigen exposure on endothelin-1-induced bronchial smooth
      muscle contraction and activation of RhoA in sensitized rats.
AB  - Changes in endothelin-1 (ET-1)-induced contraction and activation of RhoA in
      bronchial smooth muscle of repeatedly antigen-challenged rats, which exhibit
      marked airway hyperresponsiveness (AHR), were examined. The ET-1-induced
      contraction of bronchial smooth muscle was significantly enhanced in the
      repeatedly antigen-challenged group. In normal control animals, ET-1 induced time
      and concentration-dependent translocation of RhoA to the plasma membrane,
      indicating activation of RhoA by ET-1 in rat bronchial smooth muscle. The level
      of ET-1-induced RhoA translocation was increased much more markedly in the AHR
      group than in the control animals. It is suggested that the augmented activation
      of RhoA observed in the hyperresponsive bronchial smooth muscle might be
      responsible for the enhanced ET-1-induced contraction of bronchial smooth muscle
      in AHR rats.

PMID- 16002998
TI  - Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic
      concepts, current controversies, and potential importance of cytosolic NADPH.
AB  - Vascular smooth muscle (VSM) derived from pulmonary arteries generally contract
      to hypoxia, whereas VSM from systemic arteries usually relax, indicating the
      presence of basic oxygen-sensing mechanisms in VSM that are adapted to the
      environment from which they are derived. This review considers how fundamental
      processes associated with the generation of reactive oxygen species (ROS) by
      oxidase enzymes, the metabolic control of cytosolic NADH, NADPH and glutathione
      redox systems, and mitochondrial function interact with signaling systems
      regulating vascular force in a manner that is potentially adapted to be involved
      in Po2 sensing. Evidence for opposing hypotheses of hypoxia, either decreasing or
      increasing mitochondrial ROS, is considered together with the Po2 dependence of
      ROS production by Nox oxidases as sensors potentially contributing to hypoxic
      pulmonary vasoconstriction. Processes through which ROS and NAD(P)H redox changes
      potentially control interactive signaling systems, including soluble guanylate
      cyclase, potassium channels, and intracellular calcium are discussed together
      with the data supporting their regulation by redox in responses to hypoxia.
      Evidence for hypothesized potential differences between systemic and pulmonary
      arteries originating from properties of mitochondrial ROS generation and the
      redox sensitivity of potassium channels is compared with a new hypothesis in
      which differences in the control of cytosolic NADPH redox by the pentose
      phosphate pathway results in increased NADPH and Nox oxidase-derived ROS in
      pulmonary arteries, whereas lower levels of glucose-6-phosphate dehydrogenase in
      coronary arteries may permit hypoxia to activate a vasodilator mechanism
      controlled by oxidation of cytosolic NADPH.

PMID- 16002999
TI  - Lysophosphatidylcholine: an enigmatic lysolipid.

PMID- 16003000
TI  - Carbon monoxide inhibits IL-17-induced IL-6 production through the MAPK pathway
      in human pulmonary epithelial cells.
AB  - Interleukin (IL)-17 is a proinflammatory cytokine that is produced by activated
      memory CD4 T cells, which regulates pulmonary neutrophil emigration by the
      induction of CXC chemokines and cytokines. IL-17 constitutes a potential target
      for pharmacotherapy against exaggerated neutrophil recruitment in airway
      diseases. As a cytoprotective and anti-inflammatory gaseous molecule, carbon
      monoxide (CO) may also regulate IL-17-induced inflammatory responses in pulmonary
      cells. Herein, we examine the production of cytokine IL-6 induced by IL-17 and
      the effect of CO on IL-17-induced IL-6 production in human pulmonary epithelial
      cell A549. We first show that IL-17 can induce A549 cells to release IL-6 and
      that CO can markedly inhibit IL-17-induced IL-6 production. IL-17 activated the
      ERK1/2 MAPK pathway but did not affect p38 and JNK MAPK pathways. CO exposure
      selectively attenuated IL-17-induced ERK1/ERK2 MAPK activation without
      significantly affecting either JNK or p38 MAPK activation. Furthermore, in the
      presence of U0126 and PD-98059, selective inhibitors of MEK1/2, IL-17-induced IL
      6 production was significantly attenuated. We conclude that CO inhibits IL-17
      stimulated inflammatory response via the ERK1/2-dependent pathway.

PMID- 16003001
TI  - Perforation of external carotid artery branch arteries during endoluminal carotid
      revascularization procedures: consequences and management.
AB  - The purpose of this article is to describe several inadvertent perforations of
      external carotid artery branches that occurred in our laboratory during planned
      carotid artery stenting procedures. When known, the mechanism of the perforation
      is described. The treatment of these complications is discussed, along with a
      more general discussion of potential embolic materials. Perforation of branch
      arteries within the external carotid artery territory during planned carotid
      revascularization is an uncommon but potentially life-threatening complication.
      This complication can occur as a result of wire or catheter placement into these
      vessels. Early recognition of the perforation, prompt treatment of the bleeding,
      and control of the patient's airway are necessary to avoid a potentially
      catastrophic outcome.

PMID- 16003003
TI  - Platelet glycoprotein IIb/IIIa inhibition as adjunctive therapy during primary
      percutaneous coronary intervention for acute ST-segment elevation myocardial
      infarction.

PMID- 16003002
TI  - The impact of GP IIb/IIIa inhibitors during primary percutaneous coronary
      intervention in acute myocardial infarction patients.
AB  - The use of glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary
      interventions (PCI) in the acute phase of myocardial infarction (AMI) is still a
      matter of debate. The aim of the present study was to compare the outcomes of
      patients with acute ST-segment elevation myocardial infarction who underwent
      primary PCI and were concomitantly treated with GP IIb/IIIa inhibitors with those
      who were not treated with these drugs. Between January 1996 and November 2003, a
      total of 418 consecutive patients underwent PCI in the setting of ST-segment
      elevation AMI. At the operator's discretion, 287 patients were concomitantly
      treated with GP IIb/IIIa inhibitors and 115 patients were not. Angiographic
      success and final TIMI 3 flow in the infarct-related artery was achieved more
      frequently in patients treated with GP IIb/IIIa inhibitors (90% vs. 77%;
      p=0.001). The in-hospital composite endpoint of death, reinfarction and bleeding
      complications was significantly better in patients treated with GP IIb/IIIa
      inhibitors (4% vs. 12%; p=0.005). Furthermore, the adjusted 12-month survival
      rate was significantly better in these patients (RR: 2.99, CI: 1.29-6.9; p=0.01).
      Therefore, adjunctive therapy with GP IIbIIIa inhibitors during primary PCI is
      associated with improved short-term outcomes and one-year survival without an
      increased risk of bleeding.

PMID- 16003004
TI  - Intracoronary brachytherapy for in-stent restenosis using long sources reduces
      restenosis.
AB  - Edge restenosis (candy wrapper effect) and late thrombosis remain a problem in
      various randomized intracoronary brachytherapy (ICBT) trials for the treatment of
      in-stent restenosis (ISR). Target vessel revascularization (TVR) due to target
      lesion revascularization (TLR) and edge restenosis can be decreased with the use
      of longer ICBT sources and debulking devices and has not been systematically
      studied. We analyzed 226 patients with ISR (240 vessels of 264 lesions; average
      lesion length 17.5+/-8.9 mm) who had lesion debulking followed by 90 Strontium
      (Sr) beta-irradiation using the Novoste Betacath system (30 mm source in 144
      vessels and 40 mm source in 96 vessels). Dual antiplatelet therapy was
      recommended for one year. At follow-up of 12+/-2 months, clinical TVR occurred in
      9.7%, with TLR in 7.1% and non-TLR in 2.6% of cases. There was no delayed or late
      subacute thrombosis. Beta-irradiation using a longer 90Sr source after lesion
      modification with cutting balloon (CB) and or rotational atherectomy (RA), along
      with the use of long-term dual antiplatelet therapy is safe and associated with
      single-digit clinical restenosis.

PMID- 16003005
TI  - Cost of care for new-onset acute coronary syndrome patients who undergo coronary
      revascularization.
AB  - OBJECTIVES: This study examines demographic, health characteristics, and total
      health care utilization in acute coronary syndrome (ACS) patients who underwent
      coronary revascularization within the first year of follow-up. BACKGROUND:
      Revascularization during or after the index ACS event is becoming more common,
      and it is important to further characterize these patients. METHODS: A
      retrospective claims analysis was conducted (July 1, 1999-June 30, 2001) with new
      onset ACS patients, defined as an emergency room visit or hospitalization with an
      ICD-9 code for unstable angina (UA) or acute myocardial infarction (AMI), but
      without an ACS claim in the previous 6 months. Patients were followed up to 12
      months to identify total resource utilization (medical, pharmacy,
      revascularization procedures). RESULTS: A total of 6,929 patients were included
      and 69% had revascularization performed during the index hospitalization. Mean
      age was 55 years; 72.9% were male. Revascularization was percutaneous coronary
      intervention (PCI) in 5,002 and bypass surgery in 1,927. The index ACS event was
      AMI in 48.9%; 13.5% had both AMI and UA. Total first-year cost was 210.7 million
      dollars (30,402 dollars per patient); hospitalization costs were 161.7 million
      dollars (23,331 dollars per patient). During follow-up, 75.5% received a statin,
      75.8% a beta-blocker, and 63.5% of all patients received clopidogrel (84.8% of
      PCI patients). Mean days of clopidogrel therapy were 83.5. CONCLUSIONS: Early
      revascularization is a frequent therapeutic strategy in these relatively young
      managed care patients. The majority of costs were medical and a majority of
      procedures were PCI. Many patients experienced AMI as their initial
      cardiovascular event. Drug utilization of statins, beta-blockers, and
      clopidogrel, according to practice guidelines, was acceptable.

PMID- 16003006
TI  - Percutaneous transulnar artery approach for diagnostic and therapeutic coronary
      intervention.
AB  - While the transradial approach is now a well-established alternative to the
      conventional femoral approach for cardiac catheterization, the ulnar artery is
      rarely used. The objective of this prospective study was to evaluate the
      feasibility and safety of transulnar catheterization for routine diagnostic and
      therapeutic coronary interventions. Among 210 consecutive patients referred for
      diagnostic coronary angiography and or angioplasty and screened for
      appropriateness of the ulnar approach, 172 (172 of 210, 82%) underwent attempted
      ulnar artery catheterization, which was successful in 158 (158 of 172, 91%). The
      173 procedures successfully performed via the ulnar approach included 122
      diagnostic coronary angiographies, 38 coronary angiographies followed by
      angioplasty, and 13 elective angioplasties. Access site complications consisted
      of one case each of silent ulnar artery thrombosis, pseudoaneurysm, and hematoma
      due to ulnar artery wall rupture during an unsuccessful catheterization attempt.
      No cardiac or systemic complications were recorded. The transulnar approach
      appears feasible and safe for routine coronary diagnostic and therapeutic
      interventions.

PMID- 16003007
TI  - Late outcomes after pulmonary valve balloon dilatation in neonates, infants and
      children.
AB  - OBJECTIVES: This review was designed to document late outcomes after percutaneous
      balloon dilation (PBD) of the pulmonary valve (PV) on infants and children.
      BACKGROUND: PBD is the treatment of choice for PV stenosis. While short and
      intermediate term results are excellent, late outcomes, with respect to growth of
      the right heart are poorly defined. METHODS: Clinical data and serial
      echocardiograms were reviewed for children who had PBD between 1984 and 1992.
      RESULTS: One-hundred and fifty children were identified. PV gradients decreased
      from 62+/-29 to 23+/-20 mmHg (p<0.0001) and remained low during a mean follow-up
      of 11.9+/-3.1 (range 3.7 to 19.3 years). Freedom from re-intervention at 1, 10
      and 15 years were: 90%, 83%, and 77%. Pulmonary regurgitation (PR) increased
      during follow-up such that 57% of children had moderate or severe PR at last
      follow-up. These children tended to have a smaller body surface area (0.52 vs.
      0.82 m2, p=0.04), were younger (3.1 vs. 5.9 years, p=0.004), and less likely to
      be syndromic (p=0.04). Only children with severe PR demonstrated a significant
      increase in right ventricular (RV) size. Tricuspid and pulmonary annuli grew with
      the child's growth, the PV demonstrating catch-up growth (PV z-score: negative
      1.3 vs. negative 0.7 at last follow-up, p=0.04). CONCLUSIONS: Following PBD in
      childhood, gradient reduction persists and RV structures grow appropriately in
      the majority of children. Although late PR occurs commonly, it is well tolerated.
      While life-long follow-up is essential, excellent outcome can be anticipated.

PMID- 16003008
TI  - Balloon pulmonary valvuloplasty in children.

PMID- 16003009
TI  - Plastic bronchitis occurring late after the Fontan procedure in a child:
      treatment with stent implantation in the left pulmonary artery.

PMID- 16003010
TI  - Placement of a sirolimus-coated stent in the distal left internal mammary artery
      of an 8-year-old boy.

PMID- 16003011
TI  - Acute myocardial infarction in a patient with pheocromocytoma and
      neurofibromatosis.

PMID- 16003012
TI  - Intragraft nicardipine prophylaxis to prevent no-reflow in triple-vessel
      saphenous vein graft intervention.

PMID- 16003013
TI  - Hybrid long-term temporary pacing.
AB  - Prolonged temporary pacing is associated with frequent complications. We describe
      a patient with aortic endocarditis and acquired tri-fascicular block in whom back
      up pacing was indicated. Using a Seldinger technique via a subclavian approach, a
      permanent active-fixation lead was positioned in the right ventricle. The lead
      was tunnelled subcutaneously for 6 cm, and the proximal end was connected to a
      standard single chamber pulse generator. The procedure was well tolerated and
      over a period of four months there were no complications or infection. The PR
      interval subsequently reduced in duration to 200 ms and as no episodes of AV
      block had occurred, the lead was easily removed with retraction of the helix and
      gentle traction.

PMID- 16003014
TI  - Concurrent percutaneous valvuloplasty of mitral and tricuspid valve stenoses.

PMID- 16003015
TI  - Posterior descending artery as a continuity from the left anterior descending
      artery.

PMID- 16003016
TI  - The efficacy of sirolimus-eluting stents versus bare metal stents for diabetic
      patients undergoing elective percutaneous coronary intervention.
AB  - BACKGROUND: Diabetes mellitus is a well-known risk factor for future adverse
      cardiac events after coronary intervention with conventional metal stents. In
      this study, the impact of sirolimus-eluting stents (SES) were evaluated in a
      consecutive group of diabetic patients undergoing elective percutaneous coronary
      treatment and compared to a population treated with bare metal stents. METHODS
      AND RESULTS: From April 2002, a policy of routine SES implantation has been
      instituted in our hospital. During 1 year of enrollment, a total of 112
      consecutive diabetic patients with de novo coronary lesions were electively
      treated with SES (SES group). A similar group for comparison comprised 118
      consecutive patients treated with bare metal stents in the preceding period (the
      pre-SES group). After 1-year follow-up, the cumulative rate of major adverse
      cardiac events (death, myocardial infarction, and any repeat revascularization)
      was 17.3% in the SES group versus 30.2% in the pre-SES group (hazard ratio, 0.54
      [95% confidence interval, 0.32-0.91]; p = 0.02), mainly due to a marked reduction
      in the need for repeat revascularization (10.2% versus 23.5%; hazard ratio, 0.40
      [95% confidence interval, 0.21-0.78]; p = 0.007). CONCLUSIONS: Routine
      utilization of SES for diabetic patients significantly reduces the rate of
      adverse cardiac events at 1 year compared to bare metal stents.

PMID- 16003017
TI  - Evolving use of drug-eluting stents in diabetic patients.

PMID- 16003018
TI  - Safety and efficacy of a new filter-based protection system for aorto-coronary
      bypass graft interventions: the ev3 Spider device.
AB  - PURPOSE: Treatment of aorto-coronary bypass grafts without a protection devices
      is associated with a high incidence of ischemic events. The Spider(R) system is a
      new protection device. METHODS AND RESULTS: We included 40 consecutive patients
      with 50 lesions and stenosis > 50% in bypass grafts. Follow-up was performed
      according to clinical records and by phone call after 30 days. Final TIMI flow 2
      or 3 was observed in 97.5% of the patients, and no-reflow occurred in 10% without
      incidence of macroembolism. The technical success rate was 92.5%. A new rise of
      creatine kinase or troponin was observed in 27.5% after treatment, but 8 of 11
      patients (72.7%) had only a periprocedural rise of troponin without elevation of
      creatine kinase. Debris was found in 52.5%, MACE rate was low (10%). Both types
      of stenoses (types A and B) were embolic, we found a trend for more frequent
      entrapped debris and periprocedural elevation of ischemic markers in type B
      stenoses, but these did not reach a significant level. CONCLUSION: Using the
      Spider system is feasible, and offers a high technical success rate, no
      macroembolism, and excellent final TIMI flow, but the risk of microembolism and
      periprocedural myocardial infarction is not entirely eliminated.

PMID- 16003019
TI  - Predictors of in-hospital and 30-day complications of peripheral vascular
      interventions using bivalirudin as the primary anticoagulant: results from the
      APPROVE Registry.
AB  - BACKGROUND: Predictors of complications in peripheral percutaneous interventions
      (PPI) with bivalirudin as a base anticoagulant have not yet been defined. The
      Angiomax Peripheral Procedure Registry of Vascular Events (APPROVE) offers a
      unique opportunity to analyze predictors of complications with bivalirudin in
      PPI. METHODS: APPROVE was a prospective, open-label, multi-center clinical trial
      that assessed the feasibility of bivalirudin in renal, iliac and femoral
      interventions. Bivalirudin was administered intravenously at a dose of 0.75 mg
      per kg bolus followed by an infusion of 1.75 mg per kg per hour for the duration
      of the procedure. Glycoprotein (GP) IIb-IIIa inhibitors were permitted at the
      discretion of the treating physician. Multiple independent variables were
      included in a Logistic Regression model to determine predictors of the combined
      endpoints of ischemic (death, amputation, unplanned urgent revascularization at
      the treated site, myocardial infarction) and major bleeding or major bleeding
      alone, assessed during hospitalization and at 30 days. RESULTS: Predictors of in
      hospital ischemic and major bleed events were congestive heart failure (p =
      0.0173) and exchanges to larger sheath size (ELS) (p = 0.0045). The strongest
      predictor of major bleeding alone at discharge (p = 0.0041) and at 30 days (p =
      0.0016) was the number of ELS. Also, female gender (p = 0.08) and low weight
      (stratified by gender with < 80 kg versus > 92 kg for males and < 62 kg versus >
      77 kg for females) (p = 0.096) showed a trend toward predicting major bleeding at
      30 days. Of 505 patients in APPROVE, 26 patients required more than one sheath
      exchange. Of these, 24 were ELS. Despite this small number, these patients
      accounted for most of the major bleeding events that occurred (11.5% versus 1.7%
      in-hospital bleeding for the patients with ELS versus single sheath use
      respectively, and 15.4% versus 3.1% for 30-day bleeding). GP IIb-IIIa inhibitors
      (n = 22) use and thrombotic lesions (3%) were not predictors of ischemic and/or
      bleeding complications. CONCLUSION: ELS during PPI is a strong predictor of
      bleeding events when bivalirudin is used as a base anticoagulant. Female gender
      and low weight also tend to contribute to major bleeding.

PMID- 16003020
TI  - Bailout use of platelet glycoprotein IIb-IIIa inhibition during coronary stent
      implantation: observations from the ESPRIT trial.
AB  - Glycoprotein (GP) IIb/IIIa inhibitors are often used as a rescue or bailout
      therapy to manage complications arising during percutaneous coronary
      intervention, rather than as prophylactic treatment. We sought to identify the
      characteristics and outcomes of patients requiring bailout treatment. The ESPRIT
      trial randomized 2,064 patients to receive eptifibatide or placebo starting
      immediately before percutaneous coronary intervention (PCI). Bailout therapy was
      used in 77 patients: 43 (4.2%) randomized to placebo and 34 (3.3%) to
      eptifibatide (p = 0.3). Bailout therapy for thrombosis was used more often in the
      placebo group (2.1% versus 1.0%; p = 0.03). Multivariable predictors of bailout
      included a greater than or equal to 90% stenosis, or visible thrombus on the
      baseline angiogram, and no aspirin pre-treatment before PCI. However, overall the
      model predicted bailout poorly (c-index = 0.64). The need for bailout cannot be
      reliably predicted using baseline characteristics. Patients experiencing
      complications have poor clinical outcomes despite bailout use of GP IIb/IIIa
      inhibitors.

PMID- 16003021
TI  - Coronary angiography with flat panel digital detectors significantly increases
      the sensitivity for calcium detection in relation to conventional fluoroscopy:
      comparison of both systems with intravascular ultrasound.
AB  - OBJECTIVE: To compare the sensitivity and specificity for coronary calcium
      detection of two fluoroscopic systems: 1) conventional system based on image
      intensifier chains (CONV); and 2) flat panel digital detector (FPDD) system,
      using intravascular ultrasound (IVUS) as the gold standard. BACKGROUND: Coronary
      calcification represents advanced atherosclerotic disease and has implications
      during coronary interventions. Angiography has been reported to have low
      sensitivity for calcium detection compared with IVUS. METHODS: Lesion
      calcification was assessed by two different fluoroscopic systems (FPDD and CONV),
      and by IVUS. RESULTS: In two consecutive periods, a total of 200 consecutive
      patients were included, 100 in each group. Clinical characteristics were similar,
      without significant differences between groups. In the CONV group, IVUS detected
      calcium in 77% of cases, and angiography in 32%. Sensitivity was 41.6% and
      specificity 91.3%. In the FPDD group, IVUS reported calcification in 79% of
      patients, and angiography in 57%. Sensitivity was 72% (p < 0.0001 for comparison
      with CONV) and specificity was 90.4%. CONCLUSION: The new fluoroscopic systems,
      based on FPDD, considerably increase the sensitivity for calcium detection
      without detrimental effect on specificity.

PMID- 16003022
TI  - Intracoronary imaging with optical coherence tomography after cutting balloon
      angioplasty for in-stent restenosis.

PMID- 16003023
TI  - Bivalirudin as an adjunct to acute coronary intervention in post-operative
      myocardial infarction.

PMID- 16003024
TI  - Treatment of iatrogenic renal artery perforation with a covered stent and
      subsequent rheolytic thrombectomy.

PMID- 16003025
TI  - The buddy wire technique is useful in transradial coronary stenting of complex,
      calcified lesions: report of three cases.

PMID- 16003026
TI  - Acute myocardial infarction caused by late stent thrombosis after deployment of a
      paclitaxel-eluting stent.

PMID- 16003027
TI  - Mitral stenosis and percutaneous mitral valvuloplasty (part 1).
AB  - Although the incidence and severity of rheumatic mitral stenosis have declined in
      developed countries, the disease is still highly prevalent in many of the poorer
      and most densely populated areas of the globe, remaining a major public health
      issue and reflecting the socioeconomic status of the region. In the last 30
      years, mitral stenosis therapy has undergone a reorientation with the
      introduction of percutaneous mitral valvuloplasty. This manuscript is an updated
      review of percutaneous dilation of mitral stenosis in its different aspects,
      encompassing traditional techniques, technical innovations, the most significant
      case loads worldwide, an analysis of the procedure as well as immediate and late
      outcomes.

PMID- 16003028
TI  - Use of a custom-made polytetrafluoroethylene-covered stent system for the
      treatment of a coronary aneurysm involving a bifurcation.

PMID- 16003029
TI  - Treatment of complex LAD-diagonal bifurcation disease using paclitaxel drug
      eluting stents.

PMID- 16003030
TI  - Elective coronary stent implantation in a patient with unstable angina and
      thrombocytopenia.

PMID- 16003031
TI  - Diving and patent foramen ovale: time for a change in fitness to dive
      certifications?

PMID- 16003032
TI  - Consensus statement of the 1st International Exercise-Associated Hyponatremia
      Consensus Development Conference, Cape Town, South Africa 2005.

PMID- 16003034
TI  - Head injuries and concussions in soccer.

PMID- 16003035
TI  - Comparative evaluation of autologous chondrocyte implantation and mosaicplasty: a
      multicentered randomized clinical trial.
AB  - OBJECTIVE: To compare the respective performance and effectiveness of autologous
      chondrocyte implantation (ACI) and mosaicplasty at resurfacing local full
      thickness chondral defects of the knee. DESIGN: Randomized clinical trial.
      SETTING: Multicenter trial at orthopedic clinics and university hospitals
      conducted from 1997 to 2000. PATIENTS: A population of patients selected
      according to eligibility criteria of age, traumatic origin of the defect, its
      localization, size, and gravity, and above all, no previous surgical treatment of
      the lesion. Forty-seven patients were randomly assigned to ACI or mosaicplasty
      and subjected to arthroscopic debridement of the lesion at the time of
      enrollment. They were called for surgery 6 months after the initial debridement.
      MAIN OUTCOME: Improved knee functionality as assessed by repeated clinical
      evaluation based on the International Knee Documentation Committee Scale and the
      Lysholm Knee Scoring Scale. RESULTS: Fourteen patients (31.8%) experienced
      substantial improvement following the initial debridement and, being clinically
      cured, received no further treatment. Seven patients (15.9%) were lost to follow
      up. Among the 23 patients (52.3%) who could effectively be evaluated, a complete
      recovery (ie, Lysholm Knee Scoring Scale score, 90-100) was observed upon
      clinical examination in 88% of the mosaicplasty-treated patients and in 68% of
      the ACI-treated ones (P = 0.093). CONCLUSIONS: Although the low power of our
      study prevents definitive conclusions, ACI and mosaicplasty are cartilage repair
      techniques that are clinically equivalent and similar in performance. The high
      percentage of spontaneous improvement ((1/3) of the patients) observed after
      simple debridement calls into question the need for prompt surgical treatment of
      patients with lesions similar to those included in this clinical trial. Moreover,
      this finding warrants further investigation, ideally through randomized clinical
      trials in which patients subjected to debridement alone are compared with
      patients undergoing reconstructive surgery.

PMID- 16003036
TI  - No effect of eccentric training on jumper's knee in volleyball players during the
      competitive season: a randomized clinical trial.
AB  - BACKGROUND: The effect of surgery on patellar tendinopathy (jumper's knee) is
      questionable, and conservative treatment protocols have not been properly
      documented. PURPOSE: : The aim of this study was to investigate the effect of a
      newly developed eccentric training program for patellar tendinopathy in
      volleyball players during the competitive season. STUDY DESIGN: Randomized
      clinical trial. METHODS: Patients were recruited from male and female elite
      volleyball teams in Norway, and the diagnosis was based on clinical examination
      alone. Of 51 players diagnosed with patellar tendinopathy, 29 could be included
      in the study. The training group (n = 13) performed squats on a 25 degrees
      decline board as a home exercise program (3 x 15 repetitions twice daily) for a
      12-week intervention period during the final half of the competitive season. The
      eccentric (downward) component was done on the affected leg. The control group (n
      = 16) trained as usual. The primary outcome was a symptom-based questionnaire
      developed specifically for patellar tendinopathy (Victorian Institute of Sport
      Assessment score), and patients were followed up before and after the
      intervention period, as well as after 6 and 30 weeks. All subjects self-recorded
      training to document their activity level (eccentric training, volleyball
      training, matches, other training). RESULTS: There was no change in Victorian
      Institute of Sport Assessment score during the intervention period in the
      training (pre, 71.1 +/- 11.3; post, 70.2 +/- 15.4) or control group (pre, 76.4 +/
      12.1; post, 75.4 +/- 16.7), nor was there any change during the follow-up period
      at 6 weeks or 6 months. The training group completed 8.2 +/- 4.6 weekly sessions
      of eccentric training during the intervention period (59% of the recommended
      volume), and there was no difference between groups in training or competition
      load. CONCLUSION: There was no effect on knee function from a 12-week program
      with eccentric training among a group of volleyball players with patellar
      tendinopathy who continued to train and compete during the treatment period.
      Whether the training would be effective if the patients did not participate in
      sports activity is not known.

PMID- 16003037
TI  - Effectiveness of patellar bracing for treatment of patellofemoral pain syndrome.
AB  - OBJECTIVE: To determine the effectiveness of patellar bracing for treatment of
      patellofemoral pain syndrome (PFPS). DESIGN: Prospective, randomized, single
      blinded clinical trial. SETTING: Subjects recruited from the general population
      of the city of Calgary. SUBJECTS: A total of 136 subjects (79 females and 57
      males with a total of 197 affected knees) diagnosed with PFPS. INTERVENTION:
      Subjects were randomly assigned to 1 of 4 treatment groups: (1) home exercise
      program, (2) patellar bracing, (3) home exercise program with patellar bracing,
      and (4) home exercise program with knee sleeve. OUTCOME MEASURES: The outcome
      measurements were knee function (KF) and 10-cm visual analogue scale (VAS) pain
      ratings for 3 different situations: knee pain during sport activity, knee pain 1
      hour after sport activity, and knee pain after sitting with knees bent for 30
      minutes. The outcome measurements were assessed at baseline and at 3, 6, and 12
      weeks. The investigators were blinded to the treatment group of each subject.
      Calculations were made for 95% confidence intervals for the change in KF and VAS
      pain ratings from baseline measurement to 12 weeks. RESULTS: There was no
      difference in the 95% confidence intervals in the change of KF and VAS pain
      ratings among the 4 treatment groups over 12 weeks. CONCLUSIONS: Symptoms of PFPS
      improved over time in terms of pain and knee function regardless of the treatment
      group. Patellar bracing did not improve the symptoms of PFPS more quickly when
      added to a home program of leg strengthening. However, patellar bracing alone can
      improve the symptoms of PFPS.

PMID- 16003038
TI  - Protective equipment use among female rugby players.
AB  - OBJECTIVES: Our objective was to assess the prevalence of protective equipment
      use and the motivation for using protective equipment among a sample of US female
      rugby players. DESIGN/METHODS: We surveyed a convenience sample of 234 current US
      female rugby players from 14 teams participating in a US women's rugby
      tournament, obtaining self-reported demographic, rugby exposure, and protective
      equipment use information. RESULTS: Mouthguards were the most commonly used piece
      of protective equipment: 90.8% of players reported having always worn a
      mouthguard while playing or practicing rugby within their most recent 3 months of
      play. Fewer than 15% of players reported having always worn other types of
      protective equipment. Equipment use varied by playing position. Whereas over 80%
      of players in all other positions always wore a mouthguard, 66.7% of scrum halves
      reported always wearing one. Both backs and forwards reported wearing shoulder
      pads, but only forwards reported always wearing padded headgear. Mouthguards,
      padded headgear, and shoulder pads were worn "to prevent injury," whereas ankle
      braces, neoprene sleeves, and athletic tape on joints were worn "to protect a
      current/recent injury." CONCLUSIONS: This is the first study of female rugby
      players to assess the prevalence of protective equipment use by playing position
      and the motivation for using protective equipment. With the exception of
      mouthguards, US female rugby players infrequently use protective equipment.
      Protective equipment use varies by playing position. Some types of protective
      equipment appear to be used as primary prevention mechanisms, whereas others are
      used as secondary or tertiary prevention mechanisms.

PMID- 16003039
TI  - Influence of training loads on patterns of illness in elite distance runners.
AB  - OBJECTIVE: To investigate relationships between training mileage and intensity,
      and the type, incidence, severity, and duration of respiratory illness in
      distance runners, and the impact of illness on submaximal and maximal running
      performance. DESIGN: A longitudinal observational study of distance runners with
      serial monitoring of training loads and clinical patterns of illness. SETTING: A
      4-month winter training period in the Southern Hemisphere. PARTICIPANTS: A total
      of 20 highly trained (elite) male middle-distance and distance runners competing
      at the national and international levels. MAIN OUTCOME MEASURES: Training was
      quantified by mileage (km), intensity (scale, 1-5), and load (volume x
      intensity). Symptoms and signs of respiratory illness (type, duration, and
      severity) were verified by a physician at a weekly review. Performance was
      monitored by measuring submaximal and maximal oxygen uptake and time to
      exhaustion on a incremental treadmill test. RESULTS: A majority of subjects
      (15/20) experienced 1 or more episodes of respiratory illness (mean, 2.5
      episodes; range, 1-5), with 79% of symptoms classified as upper respiratory in
      origin. There were no significant differences in mean weekly mileage (P = 0.43),
      training intensity (P = 0.85), or training load (P = 0.45) between healthy
      runners and those affected by illness. Mean weekly (88 +/- 46 km) and mean
      monthly (373 +/- 163 km) mileages prior to each episode of illness were similar
      to the overall study means (95.5 +/- 36.4 km and 382 +/- 146 km). There were no
      substantial relationships between mean weekly training mileage, intensity, or
      training load and the number of illnesses reported (all r < 0.20). Neither
      submaximal nor maximal running performance was significantly affected by the
      presence of illness. CONCLUSIONS: Differences in training mileage, intensity, and
      load were not associated with the incidence of respiratory illness in highly
      trained middle-distance and distance runners. Runners with mild illness can be
      reassured that symptoms will not necessarily impair submaximal and maximal
      performance.

PMID- 16003040
TI  - Recompression treatment of Red Sea diving accidents: a 23-year summary.
AB  - OBJECTIVE: The growing popularity of diving sport has resulted in more diving
      accidents. Our objective was to characterize Red Sea divers requiring
      recompression treatment in Eilat, to recognize 23-year trends of diving
      accidents, and to facilitate appropriate administrative and treatment tools for
      diving accident in this area. DESIGN: Retrospective, uncontrolled study. SETTING:
      Recompression unit at a Red Sea medical center. PATIENTS: Charts of all divers
      treated at Eilat's recompression chamber from October 1976 to December 1999 were
      reviewed. INTERVENTIONS: Recompression treatment. RESULTS: During this period,
      annual crude numbers increased 5-fold, and a total of 453 patients were treated.
      Of them, 68% were Israelis and 32% tourists; 76% were males and 23% females; and
      21.6% were diving buddies of injured divers (omitted decompression). The mean
      diving depth causing the accident was 30.2 +/- 13.1 m, and >50% of accidents
      occurred between 11 and 30 m. Over 42% suffered from decompression sickness (DCS)
      type 2, 26% from DCS type 1, and 7% from barotraumas. Women, unlike men,
      presented predominantly DCS type 2 (54% vs. 39%; P = 0.01) and sustained DCS at
      shallower waters (25.2 +/- 9.1 m) than men (31.8 +/- 13.8 m; P < 0.0001).
      Primarily, treatment followed recompression in alternating cycles of oxygen and
      air as stipulated in US Navy Tables 5 (18.1%) and 6 (37.5%). The 48-hour case
      fatality rate was 0.09%. CONCLUSIONS: This large survey of open sea diving
      accidents accentuated the need for a national registry of diving accidents and a
      national database of diving activities.

PMID- 16003041
TI  - Athlete's heart in postmenopausal former elite endurance female athletes.
AB  - OBJECTIVE: To investigate cardiac structure and function and exercise capacity in
      senior former elite athlete women. DESIGN: Cross-sectional study. PARTICIPANTS:
      Twenty postmenopausal former elite endurance athletes and 19 age-matched
      sedentary controls. METHODS: All subjects underwent transthoracic Doppler
      echocardiography and maximal exercise test on a bicycle ergometer. MAIN OUTCOME
      MEASURES: Cardiac chamber dimensions, wall thickness, cardiac function, and
      exercise capacity. RESULTS: The athletes had a greater exercise capacity (183 +/-
      26 vs. 144 +/- 36 W; P < 0.01) compared with controls. Three of 20 (15%) athletes
      and 9 of 19 (47%) controls exhibited ST depressions during exercise test (P <
      0.05). Echocardiographic measurements demonstrated larger left ventricular
      diameter (2.9 +/- 0.3 vs. 2.6 +/- 0.2 cm/m; P < 0.01), left ventricular volume
      (64 +/- 14 vs. 54 +/- 8 mL/m; P < 0.05), right ventricular diameter (1.6 +/- 0.2
      vs. 1.4 +/- 0.2 cm/m; P < 0.01), left atrial volume (20.8 +/- 6 vs. 16.6 +/- 3.6
      mL/m; P < 0.05), and stroke volume (45 +/- 10 vs. 36 +/- 5 mL/m; P < 0.01) in
      athletes than controls, whereas interventricular septum (9.3 +/- 1.7 vs. 10.1 +/-
      1.8 mm; P > 0.05) and posterior wall thickness (9.0 +/- 1.6 vs. 9.2 +/- 1.0 mm; P
      > 0.05) did not differ between the groups. CONCLUSIONS: This study demonstrates
      cardiac enlargement without increased wall thickness in postmenopausal former
      elite endurance athlete women. Our results also indicate that long-term training
      maintains a high level of cardiovascular fitness in the aging female athletes.

PMID- 16003042
TI  - Comparison of fingertip to arterial blood samples at rest and during exercise.
AB  - OBJECTIVE: The purpose was to determine whether arterialized fingertip blood-gas
      samples are comparable to arterial samples at rest and at exercise. DESIGN:
      Repeated measures, with subjects serving as their own controls. SETTING:
      Department of Anesthesia, Montreal General Hospital, Montreal, Quebec, Canada,
      (January to April 2004). PARTICIPANTS: Fifteen healthy men (age = 25 +/- 4 y;
      weight = 76.4 +/- 11.4 kg; height = 180.7 +/- 8.0 cm; peak oxygen uptake or
      VO2peak = 46.0 +/- 9.0 mL . kg . min). MAIN OUTCOME MEASURES: Arterial blood
      gases, metabolites, electrolytes. RESULTS: Blood sampled simultaneously from the
      radial artery and warmed fingertip at rest and during 2 levels of exercise
      (vigorous 181 W or 70% VO2peak; maximal 261 W or 100% VO2peak) on a
      electronically braked ergometer. Arterial partial pressure of oxygen in blood
      combining rest and the 2 exercise levels was on average 13.6 +/- 9.0 mm Hg higher
      than arterialized fingertip samples, with the largest difference occurring at
      rest (18.8 +/- 6.5 mm Hg; 95% CI = 15.5, 22.1) and the smallest difference
      occurring at the highest level of exercise (8.3 +/- 9.2 mm Hg; 95% CI = 3.6,
      13.0; P < 0.05). The pattern for oxyhemoglobin saturation was the same, showing
      statistical differences between the sampling sites with the differences reduced
      at the highest exercise intensity. In contrast, there was no difference in
      arterial and arterialized partial pressure of carbon dioxide in blood (-1.0 +/-
      1.5 mm Hg; 95% CI = -1.4, -0.6), or plasma lactate, glucose, pH, hemoglobin, and
      electrolytes between both sampling sites at rest or at the 2 exercise levels.
      CONCLUSION: Arterialized fingertip blood samples at rest and during exercise can
      predict arterial carbon dioxide pressure, and can predict arterial plasma
      lactate, glucose, pH, hemoglobin, and electrolytes; but not arterial
      oxyhemoglobin saturation or arterial oxygen pressure.

PMID- 16003043
TI  - Road bicycle fit.

PMID- 16003044
TI  - Hereditary angioedema in a martial arts family.

PMID- 16003045
TI  - Stress fracture at the base of second metacarpal in a soft tennis player.

PMID- 16003046
TI  - Cardiorespiratory fitness attenuates mortality associated with the metabolic
      syndrome.

PMID- 16003047
TI  - Does long-term aerobic exercise slow progression of atherosclerosis?

PMID- 16003048
TI  - Muscle dysfunction and wear and tear as causes of exercise-related
      osteoarthritis: a review.

PMID- 16003049
TI  - Rehabilitation of anterior cruciate ligament injuries: a review.

PMID- 16003050
TI  - Women hydrate more than men during a marathon race.

PMID- 16003051
TI  - Bilevel noninvasive positive pressure ventilation for acute respiratory failure:
      survey of Ontario practice.
AB  - OBJECTIVE: To determine physicians' stated practices regarding the use of bilevel
      noninvasive ventilation (NIV) for acute respiratory failure and the predictors of
      practice variation. DESIGN: Cross-sectional postal survey. SETTING: Province of
      Ontario, Canada. PARTICIPANTS: Attending physicians and residents in four
      specialties at 15 teaching hospitals. INTERVENTIONS: We used literature searches
      and focus groups to design questions related to NIV utilization with respect to
      frequency, location of and indications for use, awareness of supporting
      literature, and perceived efficacy. We assessed the survey's clinical sensibility
      and reliability. We used regression analyses to evaluate practice variation among
      hospitals and specialties and to determine predictors of more frequent NIV use,
      initiation of and continued use in nonmonitored settings, and use for specific
      indications. MEASUREMENTS AND MAIN RESULTS: Three hundred eighty-five (48%) of
      808 physicians responded; 242 used NIV. The two most common indications for NIV
      use were chronic obstructive pulmonary disease and congestive heart failure. NIV
      guidelines, protocols, or policies were available in 12 of 15 hospitals. We found
      variation in NIV utilization among specialties but not hospitals. Specialty
      (critical care and respirology versus internal and emergency medicine), fewer
      years of postgraduate experience, and a greater number of noninvasive ventilators
      were predictors of more frequent NIV use (all p < or = .001). Only 6% of
      respondents reported initiation of use and continued use most frequently in
      nonmonitored settings, which increased with the number of noninvasive ventilators
      (p = .02). Physician characteristics such as awareness of the literature were
      predictive of NIV use for exacerbations of chronic obstructive pulmonary disease,
      whereas perceived NIV efficacy was predictive of use for many indications,
      including congestive heart failure. CONCLUSIONS: Self-reported practice variation
      for bilevel NIV exists among specialties but not hospitals and differs with
      respect to frequency, location of use, and use for specific indications. Some
      factors associated with variation in NIV use may be suitable targets for
      utilization improvement interventions.

PMID- 16003052
TI  - The Pediatric Multiple Organ Dysfunction Score (P-MODS): development and
      validation of an objective scale to measure the severity of multiple organ
      dysfunction in critically ill children.
AB  - OBJECTIVE: To develop and then prospectively validate an objective scale to grade
      multiple organ system dysfunction in a large population of critically ill
      children. DESIGN: Prospective, observational cohort study. SETTING: A pediatric
      intensive care unit at a tertiary care pediatric teaching hospital. PATIENTS: A
      total of 6,456 pediatric consecutive admissions (mean age 4.62 yrs) admitted to
      the pediatric intensive care unit. INTERVENTIONS: a) Identification of variables
      that could define organ dysfunction in children; b) development of a Pediatric
      Multiple Organ Dysfunction Score (P-MODS); c) correlation of the score with
      outcome at pediatric intensive care unit discharge; d) subsequent prospective
      validation. MEASUREMENTS AND MAIN RESULTS: A computer system randomly separated
      patients into two groups: a development set to create the scoring system and a
      validation set to evaluate score performance and reproducibility. Survivors and
      nonsurvivors were compared to define variables that were significantly more
      abnormal in nonsurvivors. Those variables were correlated with pediatric
      intensive care unit mortality rate. Optimal intervals for each variable were
      defined on the development set, and their performance was evaluated in the
      validation set. Descriptors for organ dysfunction were identified in five organ
      systems: cardiovascular (lactic acid), respiratory (Pa(O(2))/Fi(O(2)) ratio),
      hepatic (bilirubin), hematologic (fibrinogen), and renal (blood urea nitrogen). A
      grading scale for each variable was set from 0 to 4, corresponding to mortality
      rates of <5% and >50%, respectively. P-MODS was calculated by summing the worst
      score for all variables. Overall performance of the score was evaluated by
      generating receiver operating characteristic curves for both study sets. The
      score correlated strongly and in a graded fashion with pediatric intensive care
      unit mortality rate. In both sets (development and validation), mortality rate
      was <5% when the score was 0 and >70% at the highest score. Overall mortality
      rate was 5.9% (development set) and 5.3% (validation set). The score showed
      excellent discrimination reflected in areas under the curve: 0.81 (development
      set) and 0.78 (validation set). CONCLUSIONS: P-MODS correlated strongly with
      pediatric intensive care unit mortality in both study sets and can provide an
      objective measure for assessing organ dysfunction in the pediatric intensive care
      unit. With further study and validation across many centers, it is likely that P
      MODS could function as a quantitative, clinically relevant surrogate outcome
      measure for future therapeutic trials.

PMID- 16003053
TI  - Community-acquired bacteria frequently detected by means of quantitative
      polymerase chain reaction in nosocomial early-onset ventilator-associated
      pneumonia.
AB  - OBJECTIVE: To test whether real-time polymerase chain reaction allows for rapid
      quantitative detection of Streptococcus pneumoniae, Chlamydia pneumoniae,
      Mycoplasma pneumoniae, and Legionella pneumophila in bronchoalveolar lavage
      fluids and to determine the prevalence of these pathogens in nosocomial
      ventilator-associated pneumonia. DESIGN: Prospective epidemiologic study applying
      a new molecular biology-based diagnostic tool during a 27-month period. SETTING:
      Three medical intensive care units of a tertiary care university hospital.
      PATIENTS: One hundred patients suffering from nosocomial ventilator-associated
      pneumonia, hospitalized for > or =14 days, intubated for reasons other than
      pneumonia, and mechanically ventilated for >48 hrs. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: S. pneumoniae, M. pneumoniae, and C. pneumoniae
      were detected in bronchoalveolar lavage fluids of 100 patients in 20 (20%), three
      (3%), and two (2%) cases, respectively. There of 17 (71%) revealed no growth or
      no significant growth by conventional culture. In one patient, S. pneumoniae and
      M. pneumoniae were detected simultaneously. Corresponding colony-forming units/mL
      were partly up to 10 CFU/mL with Gram stainings showing signs of acute
      inflammation in 80%. A significant temporary correlation between the number of
      days on ventilator, development of nosocomial pneumonia, and the frequency of
      detection of these pathogens was found for day 4. CONCLUSIONS: S. pneumoniae, M.
      pneumoniae, and C. pneumoniae should be considered as causative agents in
      critically ill patients who develop early-onset nosocomial ventilator-associated
      pneumonia. Thus, empirical antimicrobial regimens should cover S. pneumoniae,
      Chlamydia, and Mycoplasma alike. Quantitative polymerase chain reaction is a fast
      diagnostic tool allowing for detection of these bacteria within 3 hrs in
      pretreated patients.

PMID- 16003054
TI  - Mathematical program for outcome prediction and therapeutic support for trauma
      beginning within 1 hr of admission: a preliminary report.
AB  - OBJECTIVES: The aims were a) to noninvasively monitor acute emergency trauma
      patients beginning within 1 hr after admission to the emergency department; b) to
      prospectively predict outcome; and c) to evaluate the relative effectiveness of
      various modes of therapy. DESIGN: Prospective outcome prediction study using a
      mathematical search and display model based on noninvasive hemodynamic
      monitoring. SETTING: A level I trauma service in a large university-run inner
      city public hospital. PATIENTS: We studied 185 consecutively noninvasively
      monitored emergency patients. INTERVENTIONS: We noninvasively monitored cardiac
      index, mean arterial blood pressure, heart rate, pulse oximetry, and
      transcutaneous oxygen and carbon dioxide tensions beginning within 1-hr after
      emergency admission. MEASUREMENTS AND MAIN RESULTS: The cardiac index, pulse
      oximetry, transcutaneous oxygen tension, transcutaneous carbon dioxide tension,
      and mean arterial blood pressure were higher in survivors than in nonsurvivors in
      the initial resuscitation period and at the hemodynamic nadir. Heart rate and
      transcutaneous carbon dioxide tension were higher in the nonsurvivors. The
      calculated survival probability in the first hour observation period of survivors
      averaged 85 +/- 14% vs. 69 +/- 16% for nonsurvivors (p = .0001).
      Misclassifications of the series as a whole were 11.3%; after excluding brain
      death from severe head injury, there were 6.4% misclassifications. A decision
      support system evaluated the effects of various therapies based on responses of
      patients with similar clinical-hemodynamic states. CONCLUSION: Noninvasive
      hemodynamic monitoring and an information system provided a feasible approach to
      predict outcome early and to evaluate prospectively the efficacy of various
      therapies.

PMID- 16003055
TI  - Cortisol antiinflammatory effects are maximal at postoperative plasma
      concentrations.
AB  - OBJECTIVE: To determine the plasma concentration of cortisol that is needed for
      maximal suppression of the systemic inflammatory response to cardiac surgery with
      cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind clinical
      study of cardiac surgical patients. SETTING: Operating room and inpatient care
      facility of a university medical center. SUBJECTS: Sixty elective cardiac
      surgical patients scheduled for coronary artery bypass graft, cardiac valve
      replacement, or both. INTERVENTIONS: Patients were randomized to receive one of
      three different hydrocortisone doses, by intravenous infusion, for 6 hrs before,
      during, and immediately after surgery while also receiving etomidate to suppress
      endogenous cortisol production. MEASUREMENTS AND MAIN RESULTS: Serial
      determinations of plasma interleukin-6 were studied as a marker of systemic
      inflammation. Measurements of interleukin-10 were used as a marker of the
      compensatory antiinflammatory response. Plasma cortisol concentrations in an
      untreated control group rose from 17 microg/dL before surgery to a mean of 43
      microg/dL by 4 hrs after surgery. A dose of hydrocortisone (4 microg/kg/min for 6
      hrs) that maintained plasma cortisol between 40 and 50 microg/dL, starting 60-90
      mins before surgery, significantly suppressed plasma interleukin-6 after surgery
      compared with control while significantly increasing plasma interleukin-10 during
      surgery. Plasma interleukin-6 after surgery was not suppressed further by
      increasing the dose of hydrocortisone to 8 microg/kg/min, although the mean peak
      plasma interleukin-10 concentration increased further compared with the group
      that received the 4 microg/kg/min hydrocortisone dose. CONCLUSIONS: At the doses
      studied, cortisol-induced suppression of plasma interleukin-6 during and after
      cardiac surgery appears to be a saturable phenomenon at the concentration of
      plasma cortisol that is normally achieved after surgery in untreated patients.

PMID- 16003056
TI  - An observational study of upper gastrointestinal bleeding in intensive care
      units: is Helicobacter pylori the culprit?
AB  - OBJECTIVE: Upper gastrointestinal bleeding (UGIB) related to stress ulcers was
      formerly a fearsome complication of intensive care. The incidence of this event
      has decreased over the years. However, the morbidity, mortality, and causes of
      UGIB, particularly the etiologic role of Helicobacter pylori infection, are still
      controversial. Therefore, we prospectively assessed the incidence of UGIB in the
      intensive care unit (ICU) and evaluated the role of H. pylori infection. DESIGN:
      A prospective observational study followed by a case-control study. SETTING:
      Seven ICUs in the Paris area, five of them located in teaching hospitals.
      PATIENTS: All patients admitted consecutively to seven ICUs during a 1-year
      period were monitored for signs of clinically relevant UGIB. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Only cases of endoscopically confirmed UGIB were
      analyzed. Patients whose hemorrhage originated from the stomach and/or duodenum
      were tested for H. pylori infection, by means of serology, histologic
      examination, and stool antigen detection. The possible association between H.
      pylori and UGIB was examined in a case-control study. Twenty-nine of the 4,341
      patients admitted to the seven ICUs during the study period had clinically
      relevant, endoscopically confirmed UGIB (incidence, 0.67%; 95% confidence
      interval, 0.56%-0.77%). Ulcers were most frequently observed endoscopically.
      Patients who bled had a higher Simplified Acute Physiology Score (SAPS II) at
      admission (mean +/- sd, 47 +/- 14 vs. 36 +/- 28; p < .001). Despite a higher in
      ICU mortality rate among patients who bled (73% vs. 16%; p < .001), death was
      never due to bleeding. H. pylori infection was more frequent in patients who bled
      than in matched controls (36% vs. 16%; p = .04). CONCLUSIONS: Clinically
      relevant, endoscopically confirmed UGIB is a rare event in the ICU setting and
      tends to occur in severely ill patients. H. pylori infection is more frequent in
      patients with gastroduodenal hemorrhage than in nonbleeding patients.

PMID- 16003057
TI  - Paradoxical responses to positive end-expiratory pressure in patients with airway
      obstruction during controlled ventilation.
AB  - OBJECTIVE: To reevaluate the clinical impact of external positive end-expiratory
      pressure (external-PEEP) application in patients with severe airway obstruction
      during controlled mechanical ventilation. The controversial occurrence of a
      paradoxic lung deflation promoted by PEEP was scrutinized. DESIGN: External-PEEP
      was applied stepwise (2 cm H(2)O, 5-min steps) from zero-PEEP to 150% of
      intrinsic-PEEP in patients already submitted to ventilatory settings minimizing
      overinflation. Two commonly used frequencies during permissive hypercapnia (6 and
      9/min), combined with two different tidal volumes (VT: 6 and 9 mL/kg), were
      tested. SETTING: A hospital intensive care unit. PATIENTS: Eight patients were
      enrolled after confirmation of an obstructive lung disease (inspiratory
      resistance, >20 cm H(2)O/L per sec) and the presence of intrinsic-PEEP (> or =5
      cm H(2)O) despite the use of very low minute ventilation. INTERVENTIONS: All
      patients were continuously monitored for intra-arterial blood gas values, cardiac
      output, lung mechanics, and lung volume with plethysmography. MEASUREMENTS AND
      MAIN RESULTS: Three different responses to external-PEEP were observed, which
      were independent of ventilatory settings. In the biphasic response, isovolume
      expiratory flows and lung volumes remained constant during progressive PEEP steps
      until a threshold, beyond which overinflation ensued. In the classic
      overinflation response, any increment of external-PEEP caused a decrease in
      isovolume-expiratory flows, with evident overinflation. In the paradoxic
      response, a drop in functional residual capacity during external-PEEP application
      (when compared to zero-external-PEEP) was commonly accompanied by decreased
      plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The
      paradoxic response was observed in five of the eight patients (three with asthma
      and two with chronic obstructive pulmonary disease) during at least one
      ventilator pattern. CONCLUSIONS: External-PEEP application may relieve
      overinflation in selected patients with airway obstruction during controlled
      mechanical ventilation. No a priori information about disease, mechanics, or
      ventilatory settings was predictive of the response. An empirical PEEP trial
      investigating plateau pressure response in these patients appears to be a
      reasonable strategy with minimal side effects.

PMID- 16003058
TI  - Pharmacokinetics and intrapulmonary concentrations of linezolid administered to
      critically ill patients with ventilator-associated pneumonia.
AB  - OBJECTIVE: To determine the steady-state plasma pharmacokinetic variables and
      epithelial lining fluid concentrations of linezolid administered to critically
      ill patients with ventilator-associated pneumonia. DESIGN: Prospective, open
      label study. SETTING: An intensive care unit and research ward in a university
      hospital. PATIENTS: Sixteen critically ill adult patients with ventilator
      associated pneumonia. INTERVENTIONS: All subjects received 1-hr intravenous
      infusions of linezolid 600 mg twice daily. After 2 days of therapy, the steady
      state plasma pharmacokinetic variables and epithelial lining fluid concentrations
      of linezolid were determined by high-performance liquid chromatography.
      MEASUREMENTS AND MAIN RESULTS: The mean +/- sd linezolid peak and trough
      concentrations were 17.7 +/- 4.0 mg/L and 2.4 +/- 1.2 mg/L in plasma and 14.4 +/-
      5.6 mg/L and 2.6 +/- 1.7 mg/L in epithelial lining fluid, respectively, showing a
      mean linezolid percentage penetration in epithelial lining fluid of approximately
      100%. The mean +/- sd area under concentration-time curve during the
      observational period (AUC0-12) was 77.3 +/- 23.7 mg x hr/L, corresponding to a
      mean AUC0-24 of 154.6 mg x hr/L. CONCLUSIONS: Our study shows satisfactory
      results, with linezolid concentrations exceeding the susceptibility breakpoint
      for Gram-positive bacteria in both plasma and epithelial lining fluid. This
      suggests that a dosage of 600 mg administered intravenously twice daily to
      critically ill patients with Gram-positive ventilator-associated pneumonia would
      achieve success against organisms with minimum inhibitory concentrations as high
      as 2-4 mg/L in both plasma and epithelial lining fluid.

PMID- 16003059
TI  - Internal medicine resident education in the medical intensive care unit: the
      impact on education and patient care of a scheduling change for didactic
      sessions.
AB  - OBJECTIVE: Modifications in residency educational programs are needed to comply
      with the work-hour limitations introduced by the Accreditation Council for
      Graduate Medical Education. The objective of this study was to determine the
      impact of rescheduling critical care didactic sessions on medicine residents'
      education during their medical intensive care unit (MICU) rotation and on
      outcomes. DESIGN: A pilot program of nonrandomized design. SETTING: A graduate
      school of medicine. PATIENTS: All patients admitted during the study periods who
      authorized their medical records to be reviewed. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We instituted a pilot program that replaced the
      daily traditional 1-hour post-rounds didactic session with an 8:00 am 30-min
      session, conducted before work rounds, on weekdays from July 2003 through
      December 2003. The residents' end-of-rotation examination scores were used to
      assess the impact on education. The pilot period residents' examination results
      were compared with the examination results from July 2002 through December 2002.
      To evaluate the effect on patient care, the Acute Physiology Score, Acute
      Physiology and Chronic Health Evaluation III score, and predicted and observed
      lengths of MICU and hospital stay of all patients during these two study periods
      were abstracted and compared. Forty-eight residents were included in each period
      of the study. The residents' performance on the examination at the end of MICU
      rotation improved when the didactic session was moved to 8:00 am (67.9 +/- 13.8
      vs. 73.9 +/- 12.1; p = .0270). The statistically significant improvement was
      limited to the first-year residents. There were 751 and 903 patients,
      respectively, admitted to the MICU during the 2002 and 2003 study periods. There
      were no significant differences in Acute Physiology Score and Acute Physiology
      and Chronic Health Evaluation III score between patients admitted during the two
      study periods. The observed hospital mortality rate was lower during the second
      period. There were no statistically significant differences in the adjusted
      length of MICU and hospital stay between the two periods. CONCLUSION: Early
      morning didactic sessions improve the educational experience of internal medicine
      residents rotating in the MICU without compromising patient care.

PMID- 16003060
TI  - The international sepsis forum consensus conference on definitions of infection
      in the intensive care unit.
AB  - OBJECTIVE: To develop definitions of infection that can be used in clinical
      trials in patients with sepsis. CONTEXT: Infection is a key component of the
      definition of sepsis, yet there is currently no agreement on the definitions that
      should be used to identify specific infections in patients with sepsis. Agreeing
      on a set of valid definitions that can be easily implemented as part of a
      clinical trial protocol would facilitate patient selection, help classify
      patients into prospectively defined infection categories, and therefore greatly
      reduce variability between treatment groups. DESIGN AND METHODS: Experts in
      infectious diseases, clinical microbiology, and critical care medicine were
      recruited and allocated specific infection sites. They carried out a systematic
      literature review and used this, and their own experience, to prepare a draft
      definition. At a subsequent consensus conference, rapporteurs presented the draft
      definitions, and these were then refined and improved during discussion.
      Modifications were circulated electronically and subsequently agreed upon as part
      of an iterative process until consensus was reached. RESULT: Consensus
      definitions of infection were developed for the six most frequent causes of
      infections in septic patients: pneumonia, bloodstream infections (including
      infective endocarditis), intravascular catheter-related sepsis, intra-abdominal
      infections, urosepsis, and surgical wound infections. CONCLUSIONS: We have
      described standardized definitions of the common sites of infection associated
      with sepsis in critically ill patients. Use of these definitions in clinical
      trials should help improve the quality of clinical research in this field.

PMID- 16003061
TI  - Survivors of acute respiratory distress syndrome: relationship between pulmonary
      dysfunction and long-term health-related quality of life.
AB  - BACKGROUND: Patients who survive acute respiratory distress syndrome (ARDS) often
      report decreased general health-related quality of life (HRQOL) following
      hospital discharge. The extent to which this impairment is due to pulmonary or
      nonpulmonary causes is unclear. We describe the pattern of recovery of patients
      surviving ARDS to illuminate any relationships between lung spirometry values,
      pulmonary symptoms, and overall HRQOL. METHODS: Seventy-three survivors of ARDS
      were enrolled in a 12-month follow-up study as part of a phase III randomized,
      multicenter trial. Patients were contacted at 3, 6, and 12 months after
      enrollment to complete generic and disease-specific HRQOL questionnaires and have
      lung spirometry tests performed. RESULTS: For all domains of the Medical Outcomes
      Study Short Form-36 (SF-36) and the St. George's Respiratory Questionnaire (SGRQ)
      at all time intervals, survivors of ARDS had significantly lower scores than age-
      and sex-matched population values. Over the 12-month follow-up period, we
      observed significant improvements to the overall Physical Component Score, but
      the Mental Component Score of the SF-36 and the SGRQ scores were not
      statistically different. Physical performance measures suggested that by 12
      months, 57% had not returned to "normal activity." At 12 months, lung spirometry
      tests demonstrated mild abnormalities that were stable over time (64% and 49% had
      <80% predicted forced expiratory volume in 1 sec [Fev1] and forced vital capacity
      [Fvc], respectively). At 12 months, the forced expiratory volume in 1 sec
      correlated strongly with the physical function domain of the SF-36 (correlation
      coefficient = 0.601; p < .01) and moderately with all domains of the SGRQ
      (correlation coefficient = -0.36, -50; p < .01 in all cases). In addition, there
      were several strong to moderate correlations between the various domains of the
      SF-36 and SGRQ. CONCLUSIONS: Survivors of ARDS have considerable respiratory
      symptoms and reduced HRQOL that is still prevalent at 12 mos following onset of
      injury. There are significant correlations between lung spirometry, pulmonary
      symptoms, and overall HRQOL, thus suggesting the acute lung injury/ARDS is
      causally contributing to the observed long-term outcome.

PMID- 16003062
TI  - Role of preexisting disease in patients' perceptions of health-related quality of
      life after intensive care.
AB  - OBJECTIVES: To find out how patients perceive their health-related quality of
      life after they have been treated in an intensive care unit and whether
      preexisting disease influenced their perception. DESIGN: : Follow-up,
      quantitative, dual-site study. SETTING: Combined medical and surgical intensive
      care units of one university and one general hospital in Sweden. PATIENTS: Among
      the 1,938 patients admitted, 562 were considered eligible (>24 hrs in the
      intensive care unit, and age >18 yrs). The effect of preexisting disease was
      assessed by use of a large reference group, a random sample (n = 10,000) of the
      main intake area of the hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: During 2000-2002, data were collected from the intensive care unit
      register and from a questionnaire mailed to the patients 6 months after their
      discharge from hospital. Subjects in the reference group were sent postal
      questionnaires during 1999. Of the patients in the intensive care unit group, 74%
      had preexisting diseases compared with 51% in the reference group. Six months
      after discharge, health-related quality of life was significantly lower among
      patients than in the reference group. When comparisons were restricted to the
      previously healthy people in both groups, the observed differences were about
      halved, and when we compared the patients in the intensive care unit who had
      preexisting diseases with subjects in the reference group who had similar
      diseases, we found little difference in perceived health-related quality of life.
      In some dimensions of health-related quality of life, we found no differences
      between patients in the intensive care unit and the subjects in the reference
      population. CONCLUSIONS: Preexisting diseases significantly affect the extent of
      the decline of health-related quality of life after critical care, and this
      effect may have been underestimated in the past. As most patients who are
      admitted to an intensive care unit have at least one preexisting disease, it is
      important to account for these effects when examining outcome.

PMID- 16003063
TI  - Deep venous thrombosis in medical-surgical critically ill patients: prevalence,
      incidence, and risk factors.
AB  - OBJECTIVE: Critically ill patients may be at high risk of venous thromboembolism.
      The objective was to determine the prevalence, incidence, and risk factors for
      proximal lower extremity deep venous thrombosis among critically ill medical
      surgical patients. DESIGN: Prospective cohort. SETTING: Closed university
      affiliated intensive care unit. PATIENTS: We enrolled consecutive patients > or
      =18 yrs of age expected to be in intensive care unit for > or =72 hrs. Exclusion
      criteria were an admitting diagnosis of trauma, orthopedic surgery, pregnancy,
      and life support withdrawal. INTERVENTIONS: Interventions included bilateral
      lower extremity compression ultrasound within 48 hrs of intensive care unit
      admission, twice weekly, and if venous thromboembolism was clinically suspected.
      Thromboprophylaxis was protocol directed and universal. We recorded deep venous
      thrombosis risk factors at baseline and daily, using multivariate regression
      analysis to determine independent predictors. Patients were followed to hospital
      discharge. RESULTS: Among 261 patients with a mean Acute Physiology and Chronic
      Health Evaluation II score of 25.5 (+/-8.4), the prevalence of deep venous
      thrombosis was 2.7% (95% confidence interval 1.1-5.5) on intensive care unit
      admission, and the incidence was 9.6% (95% confidence interval 6.3-13.8) over the
      intensive care unit stay. We identified four independent risk factors for
      intensive care unit-acquired deep venous thrombosis: personal or family history
      of venous thromboembolism (hazard ratio 4.0, 95% confidence interval 1.5-10.3),
      end-stage renal failure (hazard ratio 3.7, 95% confidence interval 1.2-11.1),
      platelet transfusion (hazard ratio 3.2, 95% confidence interval 1.2-8.4), and
      vasopressor use (hazard ratio 2.8, 95% confidence interval 1.1-7.2). Patients
      with deep venous thrombosis had a longer duration of mechanical ventilation (p =
      .03), intensive care unit stay (p = .005), and hospitalization (p < .001) than
      patients without deep venous thrombosis. CONCLUSIONS: Despite universal
      thromboprophylaxis, medical-surgical critically ill patients remain at risk for
      lower extremity deep venous thrombosis. Further research is needed to evaluate
      the risks and benefits of more intense venous thromboembolism prophylaxis.

PMID- 16003064
TI  - A wet-primed extracorporeal membrane oxygenation circuit with hollow-fiber
      membrane oxygenator maintains adequate function for use during cardiopulmonary
      resuscitation after 2 weeks on standby.
AB  - OBJECTIVE: To assess the durability of wet-preprimed extracorporeal membrane
      oxygenation (ECMO) circuits for potential use in resuscitation after a 2-wk
      period of storage. DESIGN: Experimental laboratory study. SETTING: Tertiary care
      pediatric cardiac intensive care unit. SUBJECTS: None. INTERVENTIONS AND
      MEASUREMENTS: 14 ECMO circuits (polyvinyl chloride and super-Tygon tubing with
      hollow-fiber oxygenator, Medos Hilite 800LT) were primed with crystalloid under
      sterile conditions and stored for 0 (control, n = 4), 7 (n = 5) and 14 (n = 5)
      days and maintained at 8 degrees C on pump at 10 rpm and gas flow at 0.2 L/min.
      Daily samples were inspected for plasticizers by means of high-performance liquid
      chromatography and for microorganisms by culture and polymerase chain reaction
      techniques. After storage, the oxygenators were primed with red blood cells
      (hemoglobin, 12 g/dL) and tested in vitro with a deoxygenator according to
      Association for Advancement of Medical Instrumentation standards. Oxygen and
      CO(2) transfer rates were calculated by standard formulae at maximum blood flow
      (800 mL/min) and maximum sweep gas flow (1.6 L/min). MAIN RESULTS: Oxygen
      transfer was linearly related to venous oxygen saturation, increasing by 11
      mL/min for each 10% decrease in venous oxygen saturation. Estimated oxygen
      transfer at venous oxygen saturation of 60% was 45.8 mL/min (95% confidence
      interval [CI], 43.5-48.1) for controls, 51.0 mL/min (95% CI, 48.9-53.2) for 7-day
      oxygenators, and 49.0 mL/min (95% CI, 47.8-50.1) for 14-day oxygenators. CO(2)
      transfer declined to 29.2 mL/min at 14 days of storage, a mean fall of 11.5
      mL/min (95% CI, 4.2-18.7) in comparison with 7-day storage. All circuits were
      free from microbes/microbial DNA. Plasticizer levels fell below the lower limit
      of detection (0.003 microg/mL) at 7 and 14 days. CONCLUSIONS: A wet-preprimed
      ECMO circuit with hollow-fiber membrane oxygenator can be stored for up to 2 wks
      with adequately preserved function if prepared appropriately. These data may
      improve safe access to rapid-response ECMO support.

PMID- 16003066
TI  - Hyperoxia in lethal methemoglobinemia: effects on oxygen transport, tissue
      oxygenation, and survival in pigs.
AB  - BACKGROUND: Treatment of severe methemoglobinemia includes the avoidance of
      methemoglobin-inducing drugs, the application of methylene blue, and the
      administration of supplementary oxygen. However, the efficacy of the latter on
      oxygen transport, tissue oxygenation, and survival in the treatment of extreme
      methemoglobinemia is ambiguous. The objective was to assess whether using
      hyperoxic ventilation as the sole therapeutic intervention (i.e., ventilation
      with pure oxygen, Fio2 1.0) improves the short-term (6-hr) survival rate during
      otherwise lethal methemoglobinemia. DESIGN: Prospective, randomized, controlled
      study. SETTING: Experimental animal laboratory of a university hospital.
      SUBJECTS: Fourteen anesthetized, mechanically ventilated pigs. INTERVENTIONS:
      After induction of profound methemoglobinemia (60 +/- 2%) by the injection of 15
      mg/kg 4-dimethylaminophenol, artificial ventilation either was continued with
      room air (G 0.21, n = 7) or was changed over to hyperoxic ventilation (G 1.0, n =
      7). A constant level of methemoglobinemia was maintained by continuous infusion
      of 4-dimethylaminophenol throughout a 6-hr follow-up period. MEASUREMENTS AND
      MAIN RESULTS: All animals died within the 6-hr follow-up period, but survival
      time was prolonged in animals ventilated with pure oxygen (G 0.21, 105 +/- 30
      mins; G 1.0, 210 +/- 64 mins, p < .05). No differences were encountered between G
      0.21 and G 1.0 with respect to the investigated variables of macrohemodynamics,
      oxygen transport, and tissue oxygenation. CONCLUSIONS: Hyperoxic ventilation has
      negligible effects on oxygen transport and tissue oxygenation during lethal
      methemoglobinemia; nevertheless, survival was increased without severe adverse
      reactions provoked by hyperoxic ventilation.

PMID- 16003065
TI  - Effect of chemically modified tetracycline on transforming growth factor-beta1
      and caspase-3 activation in liver of septic rats.
AB  - OBJECTIVES: We have previously demonstrated that hepatic matrixmetalloproteinase
      (MMP)-9 and gelatinase activity increased significantly after sepsis, and
      pretreatment with chemically modified tetracycline (CMT-3) inhibited these
      expressions and improved survivability. It has been established that MMP-9
      release from hepatic nonparenchymal cells activates transforming growth factor
      (TGF)-beta1, which in turn catalyzes the conversion of procaspase-8 into active
      caspase-8. Caspase-8 activates caspase-3, which in turn degrades fibronectin and
      focal adhesion kinase and leads to disruption of hepatic architecture and
      integrity. We have been interested in investigating the role of posttreatment
      with CMT-3 on hepatic MMP-9, TGF-beta1, and caspase-3 activity following sepsis.
      DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male
      Sprague-Dawley rats. INTERVENTIONS: In this study, sepsis was induced in rats by
      cecal ligation and puncture (CLP), and 2 hrs later, half of the rats received CMT
      3 (25 mg/kg), whereas the other half received vehicle by gavage. Twenty-four and
      48 hrs after sepsis induction, blood and liver samples were collected.
      MEASUREMENTS AND MAIN RESULTS: Plasma glutamic oxaloacetic transaminase (GOT) and
      glutamic pyruvic transaminase (GPT) levels were determined by enzymatic method,
      and the activation states of hepatic MMP-9, MMP-2, tissue inhibitor of
      metalloproteinase (TIMP)-1, TGF-beta1, and caspase-3 were determined by Western
      immunoblotting. Plasma GOT, GPT, and hepatic MMP-9 activity increased 2.5-fold,
      and TFG-beta1 and caspase-3 activity increased 1.5- to 2-fold at 24 hrs and 48
      hrs post-CLP; CMT-3 treatment blocked these increases. Furthermore, CMT-3
      treatment also led to increased TIMP-1 level, an in vivo inhibitor of MMP-9. MMP
      2 level was unaffected by CLP. The 24-hr and 48-hr mortality rates for CLP rats
      were 29% and 50%, whereas posttreatment with CMT-3 resulted in 0% mortality.
      CONCLUSIONS: Our results are consistent with an MMP-9-induced caspase-3
      activation in response to CLP. CMT-3 posttreatment increased TIMP-1 level and
      thereby inhibited MMP-9, which in turn decreased TGF-beta1 and caspase-3
      signaling pathways and improved survivability in septic rats.

PMID- 16003067
TI  - Ubiquitin immunoreactivity in cerebrospinal fluid after traumatic brain injury:
      clinical and experimental findings.
AB  - OBJECTIVE: Recent data indicate that ubiquitin is increased in serum after trauma
      and might regulate immune functions. Its cellular source is unknown. Because
      there have been no previous studies after traumatic brain injury (TBI), we
      determined whether ubiquitin immunoreactivity is increased in cerebrospinal fluid
      (CSF) after TBI. DESIGN AND SETTING: Prospective observational study of patients,
      with a subsequent interventional study of animals. SUBJECTS: The subjects were 14
      patients with TBI, five patients with nontraumatic subarachnoid hemorrhage, ten
      nonneurologic controls, and seven cross-bred swine. INTERVENTIONS: Standardized
      TBI. MEASUREMENTS AND MAIN RESULTS: Ubiquitin immunoreactivity was analyzed by
      enzyme-linked immunosorbent assay and immunoblotting. Hemolysis was assessed
      spectrophotometrically. CSF ubiquitin levels (mean +/- sd) were 19 +/- 3 ng/mL in
      nonneurologic control patients, 81 +/- 48 ng/mL at 7 +/- 2 hrs after TBI (p =
      .002), and at the end of operation in patients with nontraumatic subarachnoid
      hemorrhage they were 104 +/- 68 ng/mL (p = .001). CSF and serum ubiquitin were
      measured for 7 days in six patients with TBI. In survivors (n = 3), CSF ubiquitin
      levels progressively recovered, whereas in nonsurvivors (n = 3), the levels
      increased until death. There was no difference in serum ubiquitin levels between
      survivors/nonsurvivors and there was no correlation between serum and CSF
      ubiquitin levels. In swine, CSF ubiquitin levels peaked at 8- to 30-fold higher
      than baseline at 60 min post-TBI and then declined with a half-life of 1.3 hrs.
      In CSF with hemolysis, peak ubiquitin levels were five-fold higher than without
      hemolysis (p < .05). Ubiquitin and hemoglobin correlations in CSF and after in
      vitro lysis of erythrocytes suggested that erythrolysis could account for no more
      than 23 +/- 16% of the CSF ubiquitin. CONCLUSIONS: CSF ubiquitin levels are
      increased more than four-fold in patients after TBI and nontraumatic subarachnoid
      hemorrhage. Peak CSF ubiquitin measurements in patients with TBI probably
      underestimated the actual peak, on the basis of data from the animal model. The
      progressive rise in CSF ubiquitin in patients with TBI who died suggests that
      lack of clearance could reflect lethal progression to irreversible brain damage.
      Erythrolysis is one potential source of CSF ubiquitin.

PMID- 16003068
TI  - Dose-dependent neuroprotection by 17beta-estradiol after cardiac arrest and
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: Despite recent advances in the treatment of cardiac arrest, neurologic
      outcome remains poor. 17beta-Estradiol (E2) has been widely shown to reduce
      damage after experimental brain injury. The present study determined whether E2
      also improves neuronal survival after experimental cardiac arrest and
      cardiopulmonary resuscitation and if any protection is dose-dependent. DESIGN: A
      randomized trial. SETTING: A research laboratory. SUBJECTS: Male C57Bl/6 mice
      weighing 20-25 g. INTERVENTIONS: Mice were randomized into one of six groups,
      receiving treatment with 0.5, 2.5, 12.5, 25, or 50 mug of E2 or vehicle 1.5 mins
      after return of spontaneous circulation. Ten minutes after induction of cardiac
      arrest (by KCl injection), cardiopulmonary resuscitation was initiated (with
      chest compressions, intravenous epinephrine, and ventilation with 100% O2).
      Additional animals of each E2-treated group were used for plasma estradiol-level
      analysis. Brains were removed for quantification of injury in the hippocampus and
      caudoputamen on day 3. MEASUREMENTS AND MAIN RESULTS: The E2 0.5 group had
      physiologic estrogen levels 60 min after injection (mean +/- se, 28 +/- 5 pg/mL),
      whereas the E2 50 group still showed supraphysiologic levels 360 min after
      administration (245 +/- 32 pg/mL). Hippocampal damage was not altered with E2
      treatment. Only posttreatment with the lowest E2 dose (E2 0.5) resulted in
      attenuated neuronal injury in the rostral and caudal caudoputamen (34 +/- 11% and
      27 +/- 11%), in comparison with vehicle (68 +/- 5, p < .05; 63 +/- 4%, p < .001).
      Higher E2 doses did not affect brain injury. CONCLUSIONS: We conclude that E2 has
      a critical dosing effect on neuronal survival, physiologic levels of E2 are
      neuroprotective after cardiac arrest/cardiopulmonary resuscitation, and acute
      exposure is sufficient for brain resuscitation.

PMID- 16003069
TI  - Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid
      hemorrhage.
AB  - OBJECTIVE: To determine the relationship between blood glucose levels (mg/dL) and
      occurrence of symptomatic vasospasm (VSP) and clinical outcomes after aneurysmal
      subarachnoid hemorrhage. DESIGN: Retrospective observational study of 352
      patients with subarachnoid hemorrhage admitted within 48 hrs of ictus between
      January 1995 and June 2002. SETTING: Neurointensive care unit. PATIENTS: Adult
      patients admitted after subarachnoid hemorrhage. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Variables included age; Hunt-Hess classification
      score; Fisher group; insulin use; infectious disease status; history of diabetes
      mellitus; and blood glucose values. Poor clinical outcome was defined by a
      modified Rankin score > or =3, and hyperglycemia was defined by a blood glucose
      level >140 mg/dL. Mean daily blood glucose values were assessed from admission to
      development of VSP or day 14. Mean admission blood glucose value, mean inpatient
      blood glucose value, insulin use, infectious disease status, Hunt-Hess
      classification score, Fisher group, and history of diabetes mellitus were entered
      in a Cox proportional hazards model. VSP occurred in 103 (29.2%) of 352 patients.
      Mean admission blood glucose values (176.6 +/- 40.3 mg/dL vs. 162.3 +/- 47.8
      mg/dL; p = .01) and mean inpatient blood glucose values (166.2 +/- 24.7 mg/dL vs.
      155.8 +/- 29.7 mg/dL; p = .001) were significantly higher in patients with VSP.
      Mean inpatient blood glucose value (relative risk, 1.01; 95% confidence interval,
      1.0-1.03; p = .04), Hunt-Hess classification score > or =3 (relative risk, 2.23;
      95% confidence interval, 1.21-3.99; p = .02), and Fisher group score of 3
      (relative risk, 1.28; 95% confidence interval, 1.15-3.1; p = .05) increased the
      risk for VSP. Hyperglycemia was associated with longer length of stay in the
      neurointensive care unit (14.5 +/- 7.1 days vs. 11.6 +/- 5.4 days; p < .001) and
      poor outcome at discharge (modified Rankin score > or =3: 58.9% vs. 18.8%; p <
      .001). CONCLUSIONS: Mean inpatient blood glucose value is associated with the
      development of VSP and may represent a target for therapy to prevent VSP and
      improve clinical outcomes.

PMID- 16003070
TI  - Serum lipids and disease severity in children with severe meningococcal sepsis.
AB  - OBJECTIVE: To evaluate the role of cholesterol and lipoproteins in children with
      severe meningococcal sepsis. DESIGN: Retrospective observational study. SETTING:
      A university-affiliated pediatric intensive care unit. PATIENTS: Fifty-seven
      patients admitted to the pediatric intensive care unit with meningococcal sepsis
      or septic shock. INTERVENTIONS: Total cholesterol, high-density lipoprotein
      (HDL), and low-density lipoprotein (LDL) concentrations were measured in serum
      samples drawn within 6 hrs after admission to the pediatric intensive care unit
      and 12, 24, 48, 72 hrs, 7 days, and 1-3 months afterward. Standard deviation
      scores of these variables (sd scores) were calculated to correct for age-related
      differences. To assess disease severity, the Pediatric Risk of Mortality (PRISM)
      score, the Sepsis-related Organ Failure Assessment (SOFA) score, and the
      Disseminated Intravascular Coagulation (DIC) score were determined as well as
      selected laboratory variables. MEASUREMENTS AND MAIN RESULTS: Ten patients died.
      Total serum cholesterol on admission was very low in all patients. This
      hypocholesterolemia was caused by low HDL concentrations but in particular by low
      LDL cholesterol levels. Eight patients had undetectable LDL levels on admission.
      Total cholesterol levels were significantly lower in nonsurvivors than in
      survivors (0.97 vs. 1.60, p = .013), whereas levels of LDL and HDL did not
      significantly differ between both groups. Total cholesterol sd scores were
      similar between survivors and nonsurvivors. Within survivors, cholesterol sd
      score was significantly lower in patients with shock compared with those with
      sepsis. The total cholesterol, HDL, and LDL levels correlated with clinical
      variables of disease severity and with levels of cytokines. Total cholesterol,
      HDL, and LDL levels normalized rapidly in survivors and were completely normal 1
      3 months after admission. CONCLUSIONS: Extremely low levels of total serum
      cholesterol, HDL, and LDL are found in the initial phase of children with severe
      meningococcal disease. Total cholesterol levels are significantly lower in
      nonsurvivors than in survivors, but not the sd score. Total cholesterol, HDL, and
      LDL levels on admission are inversely associated with disease severity.
      Hypocholesterolism is associated with hypocortisolism. The concentrations of
      total cholesterol and lipoproteins steadily increase after 24 hrs in survivors
      and are normalized 1-3 months after pediatric intensive care unit admission.

PMID- 16003071
TI  - Cardiopulmonary complications of pregnancy.
AB  - OBJECTIVES: To provide an up-to-date review of the literature on the assessment
      and management of pulmonary and cardiac conditions that may affect women during
      pregnancy and the postpartum period. DESIGN: A review of the current literature
      was performed. RESULTS: Pregnancy may be complicated by a variety of pregnancy
      specific and other cardiopulmonary complications. Management requires knowledge
      of the cardiopulmonary physiologic changes occurring in pregnancy, the pregnancy
      specific conditions that may occur, and the effect of a fetus on maternal care.
      CONCLUSIONS: Admission of the pregnant or postpartum woman to the intensive care
      unit is uncommon but may require specialized knowledge for successful management.

PMID- 16003073
TI  - Acute hyperglycemia and the innate immune system: clinical, cellular, and
      molecular aspects.
AB  - OBJECTIVE: To extract from the biomedical literature the reported effects of
      acute hyperglycemia on the major components of the innate immune system and to
      describe the clinical benefits of strict blood glucose control in certain
      patients. DATA SOURCE AND SELECTION: A Medline/PubMed search (1966 to July 2004)
      with manual cross-referencing was conducted, including all relevant articles
      investigating the effects of acutely elevated glucose levels on innate immunity.
      All publication types, languages, or subsets were searched. DATA EXTRACTION AND
      SYNTHESIS: Original and selected review articles, short communications, letters
      to the editor, and chapters of selected textbooks were extracted. Most recent and
      relevant clinical trials were reviewed for the introductory section to provide
      the clinical background to this topic. The selected bench laboratory articles
      were then divided into three main categories based on the timing of events: a)
      the early phase of the innate immune reaction; b) the cytokine network; and c)
      the phagocytic phase. The most obvious findings related to hyperglycemia included
      reduced neutrophil activity (e.g., chemotaxis, formation of reactive oxygen
      species, phagocytosis of bacteria), despite accelerated diapedesis of leukocytes
      into peripheral tissue, as well as specific alterations of cytokine patterns with
      increased concentrations of the early proinflammatory cytokines tumor necrosis
      factor-alpha and interleukin-6. Furthermore, a reduction of endothelial nitric
      oxide formation takes place, thus decreasing microvascular reactivity to dilating
      agents such as bradykinin, and complement function (e.g., opsonization,
      chemotaxis) is impaired, despite elevations of certain complement factors.
      CONCLUSIONS: Acute, short-term hyperglycemia affects all major components of
      innate immunity and impairs the ability of the host to combat infection, even
      though certain distinctive proinflammatory alterations of the immune response can
      be observed under these conditions.

PMID- 16003074
TI  - Brugada electrocardiographic pattern in a postoperative patient.
AB  - OBJECTIVE: To report the development of the Brugada electrocardiographic (ECG)
      pattern in the immediate postoperative setting. DESIGN: Case report. SETTING:
      Postanesthesia care unit at Memorial Sloan-Kettering Cancer Center. PATIENT: A 51
      yr-old white male who developed new ST-segment elevation in leads V(1)-V(3)
      typical of the ECG changes of the Brugada syndrome immediately after undergoing
      head and neck surgery for cancer. The patient was asymptomatic, and the cardiac
      enzymes and echocardiogram were normal; therefore, electrophysiologic study was
      not performed. CONCLUSIONS: We postulated that the Brugada ECG abnormalities were
      induced primarily by an increase in parasympathetic tone resulting from vagal
      nerve manipulation during deep neck dissection and partially by the fever he
      developed during the postoperative period. In addition to the more common causes
      of ST-segment elevation, the Brugada ECG pattern or syndrome should be considered
      in patients undergoing deep neck dissection who develop characteristic ECG
      changes in association with normal cardiac enzymes and echocardiogram.

PMID- 16003075
TI  - Heterogeneity and oxidation status of commercial human albumin preparations in
      clinical use.
AB  - OBJECTIVE: Human serum albumin is indicated for the treatment of shock, acute
      restoration of blood volume, and in hypoalbuminemia. Conflicting reports are
      found in the literature for the clinical safety and efficacy of human serum
      albumin administration to critically ill patients. We sought to analyze various
      commercially available albumin preparations for common, posttranslational
      modifications. DESIGN: Analysis of six commercially available albumin
      preparations for clinical use. SETTING: Trauma research laboratory. SUBJECTS:
      Commercially available human serum albumin preparations and healthy volunteers.
      INTERVENTIONS: Six commercially available human serum albumin preparations were
      analyzed by high-performance liquid chromatography. The presence of various
      posttranslational modifications was identified by positive electrospray
      ionization, time-of-flight mass spectrometry. Three different lots from three
      preparations were also analyzed to assess variability within lots from the same
      manufacturer. Also, for the purpose of comparison, human serum albumin was
      analyzed in the plasma of healthy volunteers. MEASUREMENTS AND MAIN RESULTS: The
      six human serum albumin preparations analyzed contained a high percentage (57.2
      +/- 3.3%) of bound Cys34 (oxidation of cysteine in position 34 on the human serum
      albumin molecule) in comparison to the plasma human serum albumin from healthy
      volunteers (22.9 +/- 4.8%). Lot-to-lot variability in native human serum albumin
      ranged between 4.8% and 11.2% in three separate commercial albumins. Significant
      differences existed among the various commercial preparations in other
      posttranslational modifications of albumin. CONCLUSIONS: Human serum albumin
      species with a bound Cys34 account for a large percentage of the composition of
      human serum albumin preparations used for the treatment of critically ill
      patients. Also, the variability within lots from the same manufacturer is
      significant. Consequences of the administration of these oxidized forms of human
      serum albumin to critically ill patients warrants further investigation.

PMID- 16003076
TI  - Noninvasive ventilation outside the intensive care unit: a new standard of care?

PMID- 16003077
TI  - Do we need another pediatric severity of illness score?

PMID- 16003078
TI  - Community-associated organisms in the intensive care unit--dangerous or just
      passing through?

PMID- 16003079
TI  - As we move into the new millennium.

PMID- 16003080
TI  - Detailing and clarifying cortisol's role in the metabolic response to injury.

PMID- 16003081
TI  - Helicobacter pylori and stress ulceration: an ongoing puzzle.

PMID- 16003082
TI  - Positive end-expiratory pressure in severe airflow obstruction: more than a "one
      trick pony"?

PMID- 16003083
TI  - Is the end-game penetration (of the airway)?

PMID- 16003084
TI  - Strategic learning: linking resident training to outcomes for patients.

PMID- 16003085
TI  - Acute respiratory distress syndrome and long-term outcomes: what should we
      follow?

PMID- 16003086
TI  - Health-related quality-of-life assessment after intensive care therapy:
      preexisting disease matters.

PMID- 16003087
TI  - Extracorporeal cardiopulmonary resuscitation: another piece of the jigsaw.

PMID- 16003088
TI  - Tetracycline: from antibiotic to antisepsis.

PMID- 16003089
TI  - Blood viscosity: a factor in tissue survival?

PMID- 16003090
TI  - Hyperglycemia and subarachnoid hemorrhage: the critical care part of
      neurocritical care.

PMID- 16003091
TI  - Lipopolysaccharide binding by plasma proteins: an important protective effect?

PMID- 16003092
TI  - Evaluation of the critical care patient with Brugada syndrome.

PMID- 16003093
TI  - Pharmacological aspects of albumin as a niche product in the intensive care unit.

PMID- 16003095
TI  - Would patients with more subtle signs of coagulopathy have benefited from
      treatment with activated protein C?

PMID- 16003096
TI  - Long-term cognitive impairment in sepsis survivors.

PMID- 16003097
TI  - Chlorhexidine body washing plus topical polymyxin/tobramycin.

PMID- 16003098
TI  - Elevated body temperature in the neuroscience intensive care unit.

PMID- 16003099
TI  - Simpson's paradox.

PMID- 16003101
TI  - Critical illness polyneuropathy.

PMID- 16003105
TI  - Mixing up old data.

PMID- 16003106
TI  - Clinical relevance of the LRINEC (Laboratory Risk Indicator for Necrotizing
      Fasciitis) score for assessment of early necrotizing fasciitis.

PMID- 16003110
TI  - Genetics of Parkinson's disease.
AB  - PURPOSE OF REVIEW: Parkinson's disease is the second most common
      neurodegenerative disorder and affects 2% of the population over the age of 60
      years. Due to the increasing proportion of elderly individuals in developed
      countries, Parkinson's disease and related neurodegenerative disorders represent
      a growing burden on the health care system. In the majority of cases, the cause
      of the disease is still unknown, and its elucidation remains one of the major
      challenges of the neurosciences. Recent findings in rare genetic forms of
      Parkinson's disease have allowed the development of novel animal models,
      providing a basis for a better understanding of the molecular pathogenesis of the
      disease, setting the stage for the development of novel treatment strategies.
      RECENT FINDINGS: Several novel genes for monogenic forms of Parkinson's disease,
      such as PINK-1 for an autosomal-recessive early-onset variant, and LRRK2 for a
      relatively common late-onset autosomal-dominant form have recently been
      discovered, and several novel animal models have been generated on the basis of
      genes that had been found earlier. SUMMARY: The combination of genetic,
      pathologic and molecular findings provide increasing evidence that the pathways
      identified through the cloning of different disease genes are interacting on
      different levels and share several major pathogenic mechanisms.

PMID- 16003109
TI  - The role of alpha-synuclein and tau in neurodegenerative movement disorders.

PMID- 16003111
TI  - An update on conventional and advanced magnetic resonance imaging techniques in
      the differential diagnosis of neurodegenerative parkinsonism.
AB  - PURPOSE OF REVIEW: The clinical differentiation between Parkinson's disease and
      atypical parkinsonian disorders (APD) remains a challenge for every neurologist.
      Conventional magnetic resonance imaging (MRI) and different advanced MRI
      techniques offer the potential for objective criteria in the differential
      diagnosis of neurodegenerative parkinsonism. The aim of this article is to review
      the recent literature on the role of conventional and advanced MRI techniques in
      the differential diagnosis of neurodegenerative parkinsonian disorders. RECENT
      FINDINGS: An important role of MRI is the exclusion of symptomatic parkinsonism
      due to other pathologies. Over the past two decades, conventional MRI and
      different advanced MRI techniques, including proton magnetic resonance
      spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer
      imaging (MTI) and magnetic resonance volumetry (MRV) have been found to show
      abnormalities in the substantia nigra and basal ganglia, especially in APD.
      Recent studies using MRV, MTI, DWI and 1H-MRS to discriminate Parkinson's disease
      from APD are discussed extensively. SUMMARY: Research findings suggest that novel
      MRI techniques such as MTI, DWI and MRV have superior sensitivity compared to
      conventional MRI in detecting abnormal features in neurodegenerative parkinsonian
      disorders. Whether these techniques will emerge as standard investigations in the
      work-up of patients presenting with parkinsonism requires further prospective
      magnetic resonance studies during early disease stages.

PMID- 16003112
TI  - Stem cell treatment for Parkinson's disease: an update for 2005.
AB  - PURPOSE OF REVIEW: The hallmark pathologic feature of Parkinson's disease is loss
      of melanized dopaminergic neurons within the substantia nigra pars compacta
      coupled with depletion of striatal dopamine. This is responsible for the major
      motor features of the disease. Whereas dopaminergic replacement therapy is
      effective in the early stages of the illness, chronic treatment is associated
      with motor complications and development of features that do not respond to
      levodopa therapy. Development of cellular therapies offers the potential to
      provide more effective treatment for the disease without motor complications.
      RECENT FINDINGS: Two clinical trials of fetal nigral transplantation failed to
      meet their primary endpoint and were complicated by the development of dyskinesia
      that persisted after withdrawal of levodopa ('off-medication' dyskinesia).
      However, recent studies suggest that both the limited clinical response and off
      medication dyskinesia may be related to partial, but incomplete, dopaminergic
      reinnervation of the striatum and that both might be improved by transplantation
      of more dopamine neurons. Stem cells offer the potential to provide a virtually
      unlimited supply of optimized dopaminergic neurons that can provide enhanced
      benefits in comparison to fetal mesencephalic transplants. Stem cells have now
      been shown to be capable of differentiating into dopamine neurons that provide
      benefits following transplantation in animal models of Parkinson's disease.
      However, cell survival and behavioral responses are limited. There have been
      numerous advances in enhancing the yield of dopamine neurons from stem cells, and
      promoting their survival and consequent clinical effects. SUMMARY: Stem cells
      offer great promise as a therapy for Parkinson's disease, but numerous hurdles
      remain to be overcome with stem cell therapy. The adverse event profile of
      transplantation must be determined, and societal and ethical issues addressed. As
      Parkinson's disease involves degeneration of both dopaminergic and non
      dopaminergic neurons, it also remains to be determined if transplantation of even
      the ideal dopamine neuron will improve non-dopaminergic features of the disease
      or provide benefits superior to existing therapies.

PMID- 16003113
TI  - Neuroacanthocytosis.
AB  - PURPOSE OF REVIEW: The term neuroacanthocytosis describes a group of
      phenotypically and genetically heterogeneous disorders, and thus has long been a
      source of confusion and diagnostic imprecision. It is vital to distinguish
      between the lipoprotein deficiency disorders which affect gait, but do not cause
      movement disorders or neuropsychiatric problems, and the diseases described here,
      of which these are characteristic features. This review summarizes the current
      state of knowledge regarding this group of diseases in order to facilitate
      clinical recognition, accurate diagnosis and appropriate management. RECENT
      FINDINGS: Advances in molecular medicine have enabled us to distinguish precisely
      among the disorders described under the label of neuroacanthocytosis, most
      notably between autosomal recessive chorea-acanthocytosis and the X-linked McLeod
      syndrome. This has facilitated appreciation of the range of phenotypes in each of
      the various conditions. Acanthocytosis is also found in a smaller percentage of
      cases with pantothenate kinase-associated neurodegeneration (PKAN) and
      Huntington's disease-like 2 (HDL2). An improved method of determination of
      acanthocytosis has been described, which if adopted as standard practice may
      facilitate detection of these conditions. SUMMARY: Genetic testing has led to
      increased diagnostic accuracy of the neuroacanthocytosis syndromes, which is
      essential to extend recognition of these disorders, as well as to improve
      understanding of the disease process. Most importantly, given the absence of a
      cure, it is vital for appropriate genetic counselling. Treatments, as in other
      neurodegenerative conditions, are at present limited to symptomatic therapies.

PMID- 16003114
TI  - Fragile X-associated tremor/ataxia syndrome and movements disorders.
AB  - PURPOSE OF REVIEW: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a
      multiple-system neurologic disorder caused by expansion of 55-200 CGG repeats in
      the FMR1 (fragile site mental retardation 1) gene. The presence of both
      hyperkinetic and hypokinetic movement disorders such as ataxia, tremor, and
      parkinsonism are clinical features of FXTAS. The purpose of this review is to
      summarize the description of movement disorders associated with FXTAS and to
      discuss recent observations regarding the relationship between abnormal expansion
      in the FMR1 gene and development of neurodegenerative disorders. RECENT FINDINGS:
      The clinical expression of FXTAS occasionally resembles the phenotypes of other
      idiopathic neurodegenerative disorders. However, the unique pathological feature 
      appearance of the intranuclear inclusions in the neurons and astrocytes, is
      discriminatory from those in other neurodegenerative disorders. Several studies
      found no association between the FMR1 gene premutation and development of other
      neurodegenerative disorders with similar movement disorders to FXTAS. However, a
      premutation expansion in the FMR1 gene may be a frequent genetic cause of late
      onset sporadic ataxia with magnetic-resonance-image abnormality. SUMMARY: FXTAS
      exhibits various movement-disorder phenotypes. However, the FMR1 gene premutation
      is unlikely to be a common genetic cause of neurodegenerative disorders with
      tremor or ataxia. Patients with sporadic late-onset ataxia associated with
      magnetic-resonance-image abnormality should be considered for testing for a CGG
      repeat expansion in the FMR1 gene.

PMID- 16003115
TI  - Psychogenic movement disorders.
AB  - PURPOSE OF REVIEW: This review focuses on recent studies assessing clinical
      features and laboratory findings that may help diagnose psychogenic movement
      disorders, and the ongoing controversy about the relationship of these disorders
      with preceding peripheral injury. RECENT FINDINGS: 'Organic' movement disorders
      may still be misdiagnosed as psychogenic. Probably more commonly, however,
      psychogenic movement disorders are underdiagnosed. Most features typically
      associated with recognized movement disorders, including geste antagoniste or
      treatment-induced dyskinesias, can be seen in psychogenic movement disorder, and
      abnormal movements that would not normally be considered psychogenic or produced
      by psychological factors, such as palatal tremor, may occur on a psychogenic
      basis. On the other hand, psychiatric features are sometimes seen in
      neurologically based movement disorders. The diagnostic criteria for psychogenic
      movement disorders provide a degree of diagnostic certainty based on a
      combination of clinical and psychiatric features. Laboratory investigations can
      help exclude specific diagnoses, such as Parkinson's disease with (123I)beta-CIT
      single photon emission computed tomography, and neurophysiological methods can
      demonstrate characteristic features of psychogenic movement disorders, such as
      entrainment or suppression of psychogenic tremor with contralateral hand
      movements. However, some tests reported to differentiate psychogenic from
      neurological movement disorders may have incomplete specificity; for example,
      psychogenic tremor may not always be associated with complete coherence of tremor
      frequency. An ongoing controversy surrounds movement disorders following
      peripheral injuries, but recent evidence suggests that such patients should
      always be screened for the presence of a psychogenic movement disorder. SUMMARY:
      Psychogenic movement disorder continues to be a difficult diagnosis to make and
      is likely to be underrecognized. Clinical and laboratory features are emerging,
      however, that support this diagnosis. The controversy regarding posttraumatic
      movement disorders continues, but a diagnosis of a psychogenic movement disorder
      should be actively sought in such patients.

PMID- 16003117
TI  - Functional magnetic resonance imaging of reward prediction.
AB  - PURPOSE OF REVIEW: Technical and conceptual advances in functional magnetic
      resonance imaging now allow visualization of real-time changes in oxygenation of
      deep subcortical regions, leading to rapid advances in scientific
      characterization of the neural substrates that underlie reward prediction in
      humans. RECENT FINDINGS: Neuroimaging research over the past year has focused on
      determining the necessary neural substrates for reward prediction. SUMMARY: While
      the orbitofrontal cortex has long been implicated in modality-specific reward
      representation, the ventral striatum (particularly the nucleus accumbens) may
      play a role in modality-independent representations of predicted reward. On the
      other hand, the mesial prefrontal cortex appears to play a role in representing
      reward prediction error and the dorsal caudate in linking reward to behavior.
      Theoretically, future studies will need to establish the specificity of these
      responses to reward versus punishment and anticipation versus outcome.
      Clinically, current findings suggest that patients can predict reward without a
      prefrontal cortex, but should experience difficulty correcting their behavior
      when reward predictions are violated.

PMID- 16003116
TI  - Restless legs syndrome.
AB  - PURPOSE OF REVIEW: In the review period since February 2004 a number of papers
      have been published that make significant contributions to the current
      understanding of the epidemiology, clinical assessment, pathophysiology and
      treatment of restless legs syndrome. Those with the most significant findings
      were selected and will be reviewed. RECENT FINDINGS: Several epidemiological
      studies about restless legs syndrome have become available in the review period.
      A new susceptibility locus for restless legs syndrome has been reported.
      Neuropathological studies have provided profound insights into the key role of
      iron regulation in the pathophysiology of restless legs syndrome. Several
      randomized, double-blind, placebo-controlled studies have demonstrated that
      dopamine agonists are efficacious in the treatment of restless legs syndrome. A
      few pilot treatment studies with intravenous iron have been performed. SUMMARY:
      In this paper, recent advances in the field of restless legs syndrome are
      reviewed. Special emphasis is placed on pathophysiology and treatment. Restless
      legs syndrome is still an underdiagnosed disorder. The evidence basis for its
      treatment has been considerably increased in the review period.

PMID- 16003118
TI  - Alternatives to the Wada test: a critical view of functional magnetic resonance
      imaging in preoperative use.
AB  - PURPOSE OF REVIEW: The Wada or intracarotid amobarbital procedure is already in
      its fifties and, despite its invasive character, still routine for determining
      the lateralization of language and memory prior to epileptic surgery. Among the
      new techniques available, functional magnetic resonance imaging is one of the
      most promising alternatives. This non-invasive method has several advantages
      including the possibility of mapping relevant areas within the hemispheres and
      being able to prolong examination time in case of discordant results. RECENT
      FINDINGS: Many functional magnetic resonance imaging studies have focused on
      correlations with the intracarotid amobarbital procedure as the gold standard and
      found an agreement of about 90%. More importantly, recent studies demonstrated a
      significant correlation between presurgical functional magnetic resonance imaging
      testing and postsurgical outcome for functional magnetic resonance imaging
      activations in frontal language areas. In some studies, prediction for outcome is
      already higher for functional magnetic resonance imaging than for the
      intracarotid amobarbital procedure. SUMMARY: Current data support functional
      magnetic resonance imaging as a valid alternative to the intracarotid amobarbital
      procedure. Small sample sizes in outcome studies and restrictions to certain
      sites of operation, however, still call for caution. A standardized series of
      tasks to activate the whole language and memory system paired with good
      comparability between medical centres is needed.

PMID- 16003119
TI  - Any novelty in hippocampal formation and memory?
AB  - PURPOSE OF REVIEW: Novel events tend to attract attention and become more
      effectively encoded in memory than predictable events. The hippocampus and medial
      temporal cortical regions, along with regions of the prefrontal cortex, have been
      associated with enhanced memory for novel events. This review provides an update
      on recent studies of hippocampal novelty responses in relation to memory. RECENT
      FINDINGS: Several different types of novelty have been studied. Stimulus novelty
      effects have been observed as reduced neural activity in the medial-temporal and
      prefrontal regions when the same stimulus is repeatedly presented. Contextual
      novelty effects, the detection of a stimulus or event in an unexpected context,
      is impaired in patients with hippocampal damage. Single-trial analyses of brain
      activity show that the hippocampus rapidly habituates to contextually novel
      situations. Associative novelty, the detection of new arrangements of familiar
      stimuli, has also been related to the medial-temporal regions. A division of
      labour among the medial-temporal regions has been proposed such that associative
      novelty selectively engages the hippocampus, whereas stimulus novelty is mediated
      by the perirhinal cortex. However, a simple account of when the hippocampus
      versus other medial-temporal cortical regions is recruited awaits further
      studies. Increased dopaminergic and cholinergic neurotransmission may account for
      enhanced memory encoding of novel events, and relate to structural neuronal
      changes. SUMMARY: Interindividual variability in the responsiveness of the
      hippocampal-novelty system may be genetically mediated, and personality factors
      can also play a role. A better understanding of such variability can have
      implications for interventions aimed at supporting memory and for the treatment
      of drug abuse.

PMID- 16003120
TI  - The latest on functional imaging studies of aphasic stroke.
AB  - PURPOSE OF REVIEW: Functional neuro-imaging studies of aphasic stroke offer the
      potential for a better understanding of the neuronal mechanisms that sustain
      language recovery. Conclusions, however, have been hampered by a set of
      unexpected challenges related to experimental design and interpretation. In this
      review of studies published between January 2004 and February 2005, we discuss
      imaging studies of speech production and comprehension in patients with aphasia
      after left hemisphere stroke. RECENT FINDINGS: Studies of speech production
      suggest that recovery depends on slowly evolving activation changes in the left
      hemisphere. In contrast, right hemisphere activation changes have been
      interpreted in terms of transcallosal disinhibition that do not reflect recovery
      because they occur early after stroke, in areas homologous to the lesion, and do
      not appear to correlate with the level of recovery. There have been few studies
      of auditory speech comprehension, but unlike speech production, recovery of
      speech comprehension appears to depend on both left and right temporal lobe
      activation. SUMMARY: Together, recent studies provide a deeper appreciation of
      how the neuronal mechanisms of recovery depend on the task, the lesion site, the
      time from insult and the distinction between neuronal reorganization that does
      and does not sustain recovery. Although many more studies of aphasic stroke are
      required with larger patient numbers and more focal lesion sites, we also argue
      that clinical diagnosis and treatment requires a better understanding of the
      normal variability in functional anatomy and the many neuronal pathways that are
      available to sustain each type of language task.

PMID- 16003121
TI  - Towards an explicit account of implicit learning.
AB  - PURPOSE OF REVIEW: The human brain supports acquisition mechanisms that can
      extract structural regularities implicitly from experience without the induction
      of an explicit model. Reber defined the process by which an individual comes to
      respond appropriately to the statistical structure of the input ensemble as
      implicit learning. He argued that the capacity to generalize to new input is
      based on the acquisition of abstract representations that reflect underlying
      structural regularities in the acquisition input. We focus this review of the
      implicit learning literature on studies published during 2004 and 2005. We will
      not review studies of repetition priming ('implicit memory'). Instead we focus on
      two commonly used experimental paradigms: the serial reaction time task and
      artificial grammar learning. Previous comprehensive reviews can be found in
      Seger's 1994 article and the Handbook of Implicit Learning. RECENT FINDINGS:
      Emerging themes include the interaction between implicit and explicit processes,
      the role of the medial temporal lobe, developmental aspects of implicit learning,
      age-dependence, the role of sleep and consolidation. SUMMARY: The attempts to
      characterize the interaction between implicit and explicit learning are promising
      although not well understood. The same can be said about the role of sleep and
      consolidation. Despite the fact that lesion studies have relatively consistently
      suggested that the medial temporal lobe memory system is not necessary for
      implicit learning, a number of functional magnetic resonance studies have
      reported medial temporal lobe activation in implicit learning. This issue merits
      further research. Finally, the clinical relevance of implicit learning remains to
      be determined.

PMID- 16003122
TI  - Interoception in emotional experience.
AB  - PURPOSE OF REVIEW: Many theories of emotion have postulated a close relationship
      of the feedback of physiological changes and their perception with emotional
      experience. This paper reviews recent advances in theory and brain-imaging
      research on this topic of interoception and describes a hypothetical model of the
      potential mechanisms. RECENT FINDINGS: Research from patients with spinal-cord
      injuries and pure autonomic failure suggests that emotion-related peripheral
      autonomic changes are not necessary for emotional experience. However, in support
      of a role for centrally integrated feedback from the whole body, imaging studies
      found that activations in areas commonly associated with interoception and
      emotion (anterior insula and anterior cingulate) were correlated with individual
      differences in interoception (heartbeat detection) and trait measures of emotion.
      Because recent theory distinguishes between two levels of emotional experience
      (phenomenology and awareness), this paper proposes a hypothetical model of the
      effects of interoception on phenomenology and awareness. This model classifies
      interoception into the central representation of feedback from the whole body,
      the perception of actual physiological changes as well as the perception of
      illusory changes. SUMMARY: Consistent with recent theories of emotion, evidence
      from brain imaging supports the notion that centrally integrated feedback from
      the whole body plays a role in emotional experience. Because research on neural
      correlates of emotional experience is at an early stage, the hypothesized model
      of potential causal links between interoception and emotional experience might
      serve as a helpful guide to future research.

PMID- 16003124
TI  - Advances in colonic imaging. Preface.

PMID- 16003125
TI  - Advances in colonic imaging: technical improvements in colonoscopy.
AB  - Colonoscopy has been available since the early 1970s and has become critical to
      the diagnosis and management of colorectal disorders. Features of the modern
      colonoscope and its variants are discussed, including the role of paediatric and
      variable stiffness colonoscopes for difficult insertion. The place of magnetic
      endoscope imaging systems and simulators in routine colonoscopy and training are
      examined. Finally, several recent innovations are used to illustrate how
      colonoscopy may evolve in the future, including new takes on the current
      instrument as well as potentially revolutionary pain-free, technically-easy,
      robotic devices for examination of the bowel.

PMID- 16003126
TI  - Chromo- and magnifying endoscopy for colorectal lesions.
AB  - It is essential to identify patients with premalignant or early malignant changes
      during colonoscopy. Thus, curative resection can be offered. At present,
      endoscopy can be performed with new powerful high-resolution or magnifying
      endoscopes. Comparably to the rapid development in chip technology, the optic
      features of the newly designed endoscopes offer resolutions which allow new
      mucosal surface details to be seen. In conjunction with chromoendoscopy, the
      newly discovered tool video endoscopy is much easier and more impressive than
      with conventional fibre optics. This review summarizes the value of magnifying
      endoscopy in the lower gastrointestinal tract and focuses on colorectal lesions.

PMID- 16003127
TI  - Advances in colonic imaging: new endoscopic imaging methods.
AB  - There is a need for better endoscopic visualization in specific circumstances
      like detection of flat colorectal lesions and dysplasia-screening in ulcerative
      colitis. Chromoendoscopy is a technique with proven success, but many more, novel
      endoscopic techniques are currently under investigation. In this article
      different point measurement and still imaging methods are discussed: Raman
      spectroscopy, elastic (light) scattering spectroscopy, fluorescence spectroscopy,
      optical coherence tomography and confocal laser microscopy. Furthermore, real
      time endoscopic imaging methods are discussed. These include narrow band imaging,
      fluorescence imaging and endocytoscopy. The results of fluoroscence imaging might
      be improved by application of photosensitizers or coupling of fluorescent dyes to
      tumour-related antigens (immunoscopy). Most of these techniques still have to be
      developed further and are not yet available for routine use. In our opinion, a
      combination of a red-flag technique and a microscopic technique carries an
      enormous potential.

PMID- 16003128
TI  - Colonography by computed tomography.
AB  - Computed tomographic colonography ('virtual colonoscopy') has shown promising
      results in the detection of large (> or = 10 mm) polyps in populations with a
      high prevalence of polyps. Recent studies in low prevalence populations, however,
      show variable results in sensitivity, ranging from 55% to 94% for the detection
      of patients with polyps measuring 10 mm or longer. Therefore questions have been
      raised about computed tomographic colonography as a screening method, probably
      the most valuable use of this technique. This article describes possible causes
      of these remarkable differences as well as advances in computed tomographic
      colonography.

PMID- 16003129
TI  - Colonography by magnetic resonance imaging.
AB  - Dark-lumen magnetic resonance colonography has been shown to be an appropriate
      diagnostic tool for the detection of colorectal pathologies. This review
      describes the underlying techniques of dark-lumen magnetic resonance colonography
      concerning data acquisition, image interpretation and diagnostic accuracy for the
      detection of colorectal pathologies. In addition, techniques to improve patients'
      acceptance are discussed.

PMID- 16003130
TI  - The intestinal lesion of autistic spectrum disorder.
AB  - This editorial briefly reviews the significance of lymphoid nodular hyperplasia
      in the intestinal tract of children with autistic spectrum disorder. The
      distinction between physiological and pathological lymphoid hyperplasia of the
      intestinal tract is of importance in the context of a possible causative link
      with autism. A primary intestinal lesion may occur as part of the broad spectrum
      of immunological disorders to which autistic children are prone. This could
      result in increased intestinal permeability to peptides of dietary origin which
      may then lead to disruption of neuroregulatory mechanisms required for normal
      brain development. Alternatively, there could be a primary defect in the
      translocation and processing of factors derived from the intestinal lumen. These
      possibilities deserve further investigation and should not be lost in the fog of
      the controversy regarding the role of measles/mumps/rubella vaccination in the
      aetiology of autistic spectrum disorder.

PMID- 16003131
TI  - Non-alcoholic fatty liver disease and insulin resistance.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an entity now recognized as one of
      the leading causes of asymptomatic chronic elevation of aminotransferase levels,
      which can, however, progress to more advanced forms of hepatic lesion and
      ultimately to liver failure. Insulin resistance is considered as having a central
      role in NAFLD pathogenesis, which is related with oxidative stress, abnormal
      production of cytokines and deregulation of fatty acid metabolism. In this
      article the authors make a brief review of the epidemiological data about NAFLD
      and insulin resistance, and their aetiological link, and treatment implications.

PMID- 16003132
TI  - The significance of ileo-colonic lymphoid nodular hyperplasia in children with
      autistic spectrum disorder.
AB  - BACKGROUND: Intestinal mucosal pathology, characterized by ileo-colonic lymphoid
      nodular hyperplasia (LNH) and mild acute and chronic inflammation of the
      colorectum, small bowel and stomach, has been reported in children with autistic
      spectrum disorder (ASD). AIM: To assess ileo-colonic LNH in ASD and control
      children and to test the hypothesis that there is an association between ileo
      colonic LNH and ASD in children. PATIENTS AND METHODS: One hundred and forty
      eight consecutive children with ASD (median age 6 years; range 2-16; 127 male)
      with gastrointestinal symptoms were investigated by ileo-colonoscopy. Macroscopic
      and histological features were scored and compared with 30 developmentally normal
      (non-inflammatory bowel disease, non-coeliac disease) controls (median age 7
      years; range 1-11; 25 male) showing mild non-specific colitis in 16 cases (13
      male) and normal colonic histology in 14 cases (12 male). Seventy-four ASD
      children and 23 controls also underwent upper gastrointestinal endoscopy. The
      influence on ileal LNH of dietary restriction, age at colonoscopy, and co
      existent LNH elsewhere in the intestine, was examined. RESULTS: The prevalence of
      LNH was significantly greater in ASD children compared with controls in the ileum
      (129/144 (90%) vs. 8/27 (30%), P < 0.0001) and colon (88/148 (59%) vs. 7/30
      (23%), P = 0.0003), whether or not controls had co-existent colonic inflammation.
      The severity of ileal LNH was significantly greater in ASD children compared with
      controls, with moderate to severe ileal LNH present in 98 of 144 (68%) ASD
      children versus 4 of 27 (15%) controls (P < 0.0001). Severe ileal LNH was
      associated with co-existent colonic LNH in ASD children (P = 0.01). The presence
      and severity of ileal LNH was not influenced by either diet or age at colonoscopy
      (P = 0.2). Isolated ileal LNH without evidence of pathology elsewhere in the
      intestine was a rare event, occurring in less than 3% of children overall. On
      histopathological examination, hyperplastic lymphoid follicles are significantly
      more prevalent in the ileum of ASD children (84/138; 61%) compared with controls
      (2/23; 9%, P = 0.0001). CONCLUSION: Ileo-colonic LNH is a characteristic
      pathological finding in children with ASD and gastrointestinal symptoms, and is
      associated with mucosal inflammation. Differences in age at colonoscopy and diet
      do not account for these changes. The data support the hypothesis that LNH is a
      significant pathological finding in ASD children.

PMID- 16003133
TI  - Non-alcoholic fatty liver disease and insulin resistance: importance of risk
      factors and histological spectrum.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been associated with
      several metabolic conditions (MC) and secondary causes, but the relationship
      between insulin resistance (IR) and the underlying aetiology of NAFLD has not
      been extensively explored. OBJECTIVE: To determine the frequency of IR among
      NAFLD patients and to describe IR according to risk factors and histological
      findings of the disease. METHODOLOGY: A case-series study of 64 patients with
      clinical and histological diagnosis of NAFLD. IR was calculated by homeostasis
      model assessment (HOMA) and IR was considered when HOMA > or = 3. Histological
      grades of NAFLD were: stage 1, steatosis isolated; stage 2, steatosis and
      inflammation; stage 3, steatosis and ballooning degeneration; stage 4, steatosis
      and fibrosis and/or Mallory bodies. Fibrosis was graded 0-4 (cirrhosis). RESULTS:
      IR was found in 21 (33%) patients. Among those with IR, 16 patients (76%) had
      associated MC and five patients (24%) had exposure to petrochemicals. The mean
      value of HOMA varied from 3.5 in NAFLD associated with MC to 1.6 in patients with
      exposure to petrochemicals (P < 0.03). Waist circumference was the metabolic
      factor most strongly associated with IR (P < 0.005). Steatohepatitis (NASH) was
      observed in 54 (84.3%) cases. The HOMA mean value was significantly higher in
      patients with advanced fibrosis. CONCLUSIONS: IR occurred in 33% of the NAFLD
      patients, being more frequent among those with MC than among those with exposure
      to petrochemicals. The presence of IR in cases with advanced fibrosis suggests
      that it may influence the prognosis of NAFLD.

PMID- 16003134
TI  - Serum fibrosis markers as predictors of an antifibrotic effect of interferon alfa
      in children with chronic hepatitis B.
AB  - OBJECTIVE: Interferon alfa (IFN-alpha) may retard hepatic fibrogenesis in adults
      with chronic hepatitis C. We evaluated prospectively four selected serum fibrosis
      markers before, immediately after and 12 months after IFN treatment of children
      with chronic hepatitis B (CHB). METHODS: Forty-seven children (mean age 8 years,
      range 4-16) with CHB underwent IFN-alpha treatment (3 MU t.i.w.) for 5 months.
      Fibrosis and inflammation were assessed blindly before and 12 months after the
      end of treatment. Serum laminin-2, collagen IV, MMP-2 and MMP-9/TIMP-1 complex
      were determined using automated assays. RESULTS: Twelve months after treatment
      had been discontinued levels of laminin-2, collagen IV and MMP-2 were decreased,
      and serum MMP-9/TIMP-1 complex was increased. Levels did not differ between
      sustained responders (42.5%) and non-responders. Similarly, fibrosis did not
      progress in both groups, whereas histological inflammation improved only in
      responders. CONCLUSIONS: A 5 month IFN-alpha treatment has no marked effect on
      histological liver fibrosis in children with CHB, irrespective of virological
      response. The evolution of serum fibrosis markers suggests they may be more
      sensitive to detect minor antifibrotic effects than semiquantitative follow-up
      histology.

PMID- 16003135
TI  - Impact of MELD on short-term and long-term outcome following liver
      transplantation: a European perspective.
AB  - INTRODUCTION: The Model for End-Stage Liver Disease (MELD) has been found to
      accurately predict pre-transplant mortality and is a valuable system for ranking
      patients in need of liver transplantation. Its association with post-transplant
      outcome, however, remains unclear. MATERIALS AND METHODS: We retrospectively
      studied 121 adult patients who were transplanted for non-fulminant liver failure
      between January 1991 and December 2001. MELD scores were calculated taking
      variables as close as possible prior to liver transplantation. Patients were
      stratified into two or three groups using different cut-off values of the MELD
      score. RESULTS: Indications for liver transplantation were mainly alcoholic liver
      disease (47.1%) or hepatitis C virus (19.0%). Gender distribution was male 62% vs
      female 38%. Mean age was 54 years+/-10 years. Mean MELD score was 16+/-6. Follow
      up time was 5.4 years (range, 1.6-12.3 years). The use of different MELD cut-off
      levels yielded no difference in survival at different time points. CONCLUSION:
      Higher MELD scores did not have a negative impact on patient and graft survival
      following OLT. Since MELD is good at identifying those urgently in need of liver
      transplantation and high MELD scores do not appear to have an influence on long
      term outcome, use of MELD in liver allocation seems warranted.

PMID- 16003136
TI  - Multifocal atrophic gastritis: pathogenesis and therapeutic implications.
AB  - OBJECTIVE: This study, carried out on 51 patients with multifocal atrophic
      gastritis (MAG) and 92 age and sex-matched dyspeptic controls, was designed to
      examine both exocrine (gastric acid) and endocrine (gastrin) gastric secretion
      before and after therapeutic intervention including Helicobacter pylori
      eradication and vitamin C treatment. METHODS: Fasting and gastrin-releasing
      peptide-induced gastric acid secretion, serum levels of gastrin and
      proinflammatory (IL-1beta, IL-8, TNF-alpha) as well as gastric mucosal gene
      expression of ornithine decarboxylase (ODC), cyclooxygenase 2 (COX-2) and growth
      factors (epidermal growth factor and transforming growth factor alpha) were
      determined before and after the eradication of Helicobacter pylori and therapy
      with large doses (1 g/d) of vitamin C for 3 months. RESULTS: The H. pylori
      eradication, assessed by C-urea breath test, and vitamin C therapy failed to
      reverse the histological atrophy of the gastric mucosa but improved significantly
      the functional status of the atrophied mucosa, especially its exocrine and
      endocrine secretory activities, attenuated the expression of premalignant markers
      such as ODC and COX-2, raised the production of growth factors and diminished the
      release of proinflammatory cytokines. CONCLUSIONS: These results indicate that
      MAG may be considered as an environmental disease of the gastric mucosa, whose
      functional status can be improved by the eradication of H. pylori combined with
      antioxidant therapy with large doses of vitamin C.

PMID- 16003137
TI  - Somatosensory changes in the referred pain area in patients with
      cholecystolithiasis.
AB  - BACKGROUND AND AIMS: Patients with abdominal pain provoked by acute cholecystitis
      increase the somatic sensitivity in the referred somatic pain area. Our aim in
      the present paper was to examine somatosensory changes in the referred pain area
      (previously evoked by painful attacks) in patients with uncomplicated gallstone
      disease and to evaluate the possible relation between referred pain patterns and
      clinical findings. Somatosensory changes in these areas may be important in the
      persistent pain after treatment and may help to develop treatment strategies for
      abdominal pain in the post-cholecystectomy syndrome. SUBJECTS: Forty-two patients
      with symptomatic cholecystolithiasis, confirmed ultrasonographically, were
      studied in the pain-free period. METHODS: Sensitivity and pain thresholds for
      standardized experimental sensory testing including different modalities:
      pinprick, pinching, heat, cold, pressure, and single and repeated electrical
      stimulation were studied in the area where the pain was referred to during the
      acute attacks, and in a control area on the contralateral side of the abdomen.
      RESULTS: Patients with verified cholecystolithiasis showed hyperalgesia to
      pinprick (26% of subjects, P < 0.05) and cold stimuli (21% of subjects, P < 0.05)
      in the referred pain area. There was also a significant reduction in
      sensation/pain thresholds (indicating hyperalgesia) in the referred pain area to
      single (P = 0.007/P = 0.002) and repeated electrical (P = 0.017/P = 0.043)
      stimuli, as well as in pain threshold to pinching and mechanical stimuli (P =
      0.049/P < 0.001). There were no significant relations between the hyperalgesia
      and the clinical findings. CONCLUSION: Cholecystolithiasis leads to significant
      hyperalgesia in the somatic area, where pain was referred to during the acute
      attacks. This is explained by viscero-somatic convergence mechanisms in the
      central nervous system. Therefore, central neuroplastic changes may be
      significant in diseases related to the gallbladder such as the post
      cholecystectomy syndrome.

PMID- 16003138
TI  - Colonic diverticular disease in a multiracial Asian patient population has an
      ethnic predilection.
AB  - BACKGROUND: Traditionally, diverticular disease of the colon has been attributed
      to ageing, low dietary fibre and a high intraluminal pressure. Recently, genetic
      and racial factors have also been implicated. METHODS: Four-hundred and ten
      consecutive multiracial Asian patients undergoing colonoscopy for a variety of
      bowel symptoms in a private endoscopy unit were studied for differing frequencies
      (if any) in colonic diverticular disease and concomitant abnormalities. RESULTS:
      Forty-one patients (10%) had diverticular disease. Diverticula were present in
      22/147 Chinese (15%), 14/153 Indians (9%) and 5/110 Malays (4.5%). The mean age
      of patients with diverticular disease was 55 years as compared with 51.3 years in
      those without (P = 0.12) and there was no gender difference. Thirty-six patients
      (88%) had diverticula in the right colon only, four patients (10%) exclusively in
      the left hemicolon, and one patient (2%) had bilateral involvement. Using
      regression analysis, Chinese ethnicity [odds ratio (OR)=2.11; 95% confidence
      interval (CI), 1.09-4.09; P = 0.027), constipation (OR = 2.65; 95% CI, 1.23-5.42;
      P = 0.007) and colorectal adenomas (OR = 2.65; 95% CI, 1.08-6.46; P = 0.033) were
      independently associated with diverticular disease. CONCLUSIONS: Colonic
      diverticular disease in a multiracial Asian patient population has an ethnic
      predilection and is predominantly right-sided.

PMID- 16003139
TI  - Curative ablation of a polypoid oesophageal spindle cell carcinoma with argon
      beam diathermy.
AB  - We present the successful management of dysphagia in a 90-year-old woman by argon
      beam diathermy. Symptoms were caused by a rare polypoid oesophageal spindle cell
      carcinoma. Long-term symptom relief was achieved and confirmed by post-procedural
      oesophago-gastroduodenoscopy and endoscopic ultrasound scan.

PMID- 16003165
TI  - Resistant hypertension.
AB  - Hypertension that remains above 140/90 mmHg despite the use of three
      antihypertensive drugs in a rational combination at full doses and including a
      diuretic is known as 'resistant'. The percentage of hypertensives whose condition
      is resistant varies in large part upon the setting: those seen in general
      practice show a prevalence of perhaps 5%; those seen by nephrologists, probably
      50%. This paper reviews the major causes of resistant hypertension and provides
      specific recommendations for the evaluation and management of patients with this
      threatening condition.

PMID- 16003166
TI  - The use of collagen-derived serum peptides for the clinical assessment of
      hypertensive heart disease.
AB  - Given the importance of fibrous tissue in leading to myocardial dysfunction and
      failure in hypertensive heart disease, non-invasive assessment of fibrosis could
      prove a clinically useful tool in hypertensive patients, particularly given the
      potential for cardioprotective and cardioreparative pharmacological strategies.
      In this regard, an emerging experimental and clinical experience holds promise
      for the assessment of various serum peptides arising from the metabolism of
      collagen types I and III in arterial hypertension. More specifically, the
      measurement of serum concentrations of procollagen type I carboxy-terminal
      propeptide (a peptide that is cleaved from procollagen type I during the
      synthesis of fibril-forming collagen type I) may provide indirect diagnostic
      information on both the extent of myocardial fibrosis and the ability of
      antihypertensive treatment to diminish collagen type I synthesis and reduce
      myocardial fibrosis in hypertensive patients. The available data set the stage
      for large and long-term trials to definitively validate this approach.

PMID- 16003167
TI  - Flavanols for cardiovascular health: the science behind the sweetness.
AB  - PURPOSE OF REVIEW: Cardiovascular benefits for cocoa are being claimed in the
      scientific literature with growing intensity. To date, excitement over the
      potential health benefits of flavonoids has been driven mostly by epidemiological
      studies of tea and red wine, but raw cocoa contains specific flavonoids in
      concentrations far exceeding those from most other sources. Early evidence
      supports cocoa's enhancement of endothelial function via improvement of nitric
      oxide synthesis. However, many new studies have brought more confusion than
      clarity to the enterprise. This review provides guidelines for legitimate
      research in this promising field. TOPICS OF DISCUSSION: Evidence generated from
      epidemiological studies, linking an increase in flavonoid ingestion to a
      reduction in cardiovascular events, is less convincing than data from controlled
      clinical trials. Whereas a few trials have shown evidence for an enhancement of
      endothelial function, inhibition of platelet adhesion and low-density lipoprotein
      oxidation, many studies have ignored scientific principles. Tremendous
      variability in cocoa processing, flavonoid content, measurement and dosing
      threatens the field. Valid research depends upon the precise identification and
      measurement of compounds of interest, which are probably the flavanols catechin
      and epicatechin, their oligomers and metabolites. These measures depend upon
      reliable methods of separation and quantification. Whether the monomers, dimers
      or larger flavanol oligomers, or their metabolites, are responsible for
      biological efficacy remains to be determined. Final questions surround
      bioavailability and dosing frequency. CONCLUSIONS: Evidence is mounting to
      support cardiovascular health benefits from the consumption of flavanol-rich
      cocoa. This review hopes to illuminate sound scientific principles by which
      future research in the field can be guided.

PMID- 16003168
TI  - Dietary flavonoids and cardiovascular disease: does the emperor have any clothes?

PMID- 16003169
TI  - G proteins: fine tuning of blood pressure regulation.

PMID- 16003170
TI  - Does the AT2-receptor mediate anti-atherosclerotic actions?

PMID- 16003171
TI  - Endothelial fibrinolytic function in hypertension: the expanding story.

PMID- 16003172
TI  - The structural basis of hypertension: vascular remodelling, rarefaction and
      angiogenesis/arteriogenesis.

PMID- 16003173
TI  - Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but
      also shows predicted heterogeneity.
AB  - BACKGROUND: Familial hyperaldosteronism type II (FH-II) is characterized by the
      familial occurrence of primary aldosteronism; unlike FH-I, it is not
      glucocorticoid-remediable and not associated with the hybrid CYP11B1/CYP11B2 gene
      mutation. Linkage to a 5-Mbp region of chromosome 7p22 was previously reported in
      an Australian family with eight affected members. Mutations in the exons or
      intron-exon boundaries of PRKAR1B (7p22, closely related to PRKAR1A, which is
      mutated in Carney complex) have been excluded in this family. OBJECTIVE: To
      refine the region of linkage, and to seek evidence of linkage in a South American
      family and in three other Australian families with FH-II, using seven closely
      spaced markers at 7p22. METHODS: To establish phenotypes (affected, uncertain or
      unaffected), blood pressure, plasma aldosterone and plasma renin (activity or
      concentration) were measured and the aldosterone: renin ratio (ARR) calculated.
      Individuals with consistently increased ARR underwent fludrocortisone suppression
      testing. The genotypes of the five pedigrees were analysed using seven closely
      spaced microsatellite markers at 7p22, and two-point and multipoint logarithm of
      odds (LOD) scores were calculated to assess linkage with FH-II. RESULTS: The
      combined multipoint LOD score for three families (the original Australian, the
      South American and a new Australian family) showing linkage at 7p22 was highly
      significant at 4.61 (theta = 0) for markers D7S462 and D7S517. A newly found
      recombination event in the first Australian family narrowed the area of linkage
      by 1.8 Mbp, permitting exclusion of approximately half the candidate genes in the
      originally reported locus. It was not possible to demonstrate linkage at the 7p22
      region in the remaining two Australian families. CONCLUSION: This study provides
      further evidence for linkage of FH-II to 7p22, refines the locus, and supports
      the notion that FH-II may be genetically heterogeneous.

PMID- 16003174
TI  - Relationship of alcohol consumption to 7-year blood pressure change in Japanese
      men.
AB  - OBJECTIVE: To determine the association of alcohol consumption with years-long
      blood pressure (BP) change, as well as baseline BP, adjusted for potential
      confounders. DESIGN: A prospective cohort study. SETTING: A metal-products
      factory in Toyama, Japan. PARTICIPANTS: A total of 3900 men aged 20-59 years.
      MAIN OUTCOME MEASURES: BP was measured annually for 7 years after the baseline
      examination. The generalized estimating equation method was used to analyze the
      relationship of alcohol consumption to baseline BP and average annual BP change,
      adjusting for age, yearly weight, work-related factors, and lifestyle factors,
      including the frequency of intake of 22 food groups. RESULTS: The baseline
      systolic BP after multivariate adjustment was 3.9 and 5.0 mmHg higher in drinkers
      consuming 200-299 and > or = 300 g alcohol/week, respectively, than in non
      drinkers (P < 0.001). The annual increase in systolic BP was 0.44 mmHg greater in
      drinkers consuming > or = 300 g/week than in non-drinkers after adjustment for
      age and weight change (P < 0.001), where the increase over 7 years was estimated
      to be 3.08 mmHg greater. Even after being adjusted for the frequency of intake of
      22 food groups, drinkers consuming > or = 300 g/week showed a 0.33 mmHg greater
      annual increase in systolic BP than non-drinkers (P = 0.022). Baseline diastolic
      BP was significantly associated with alcohol consumption, but annual BP change
      was not. CONCLUSIONS: An alcohol intake > or = 300 g/week was associated with
      significantly greater annual BP increase, and baseline BP was significantly
      higher in drinkers consuming > or = 200 g/week. It is necessary to limit alcohol
      intake to less than 200 g/week to prevent hypertension.

PMID- 16003175
TI  - No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a
      hypertension locus on chromosome 1p36.
AB  - OBJECTIVE: Chromosome 1p36 has been linked to essential hypertension and systolic
      blood pressure. This locus contains the chloride channel-Kb gene (CLCNKB) and the
      tumour necrosis factor receptor 2 gene (TNFRSF1B). Polymorphisms of each of these
      have shown association with hypertension, and a CLCNKB T481S variant alters
      receptor function. Here we performed association studies in a well-characterized
      cohort of hypertensives and normotensives whose blood pressure status matched
      that of both their parents. METHODS: The study involved 196 essential
      hypertensives and 321 normotensives. These were genotyped for TNFRSF1B variants T
      1710A upstream, A257G in exon 2, a CA-repeat polymorphism in intron 4, E232K and
      M196R in exon 6, and T1668G and T1690C in the 3'-untranslated region, and the
      T481S variant of CLCNKB. RESULTS: The CLCNKB T481S variant showed no association
      with hypertension. Thermodynamic modelling of the 3'-untranslated region of
      TNFRSF1B mRNA predicted that the T1668G variant alters the stem-loop structure
      and thus the mRNA stability and expression. However, neither this nor the other
      TNFRSF1B polymorphisms, either alone or after haplotype analysis, were associated
      with hypertension. Moreover, for each gene the blood pressure, body mass index,
      plasma sodium and plasma lipid concentrations were generally similar across
      genotypes. CONCLUSION: Our data fail to support previous association findings for
      TNFRSF1B and CLCNKB at the chromosome 1p36 locus implicated in hypertension.

PMID- 16003176
TI  - Genetic variations of regulator of G-protein signaling 2 in hypertensive patients
      and in the general population.
AB  - OBJECTIVES: Mice deficient in the regulator of G-protein signaling 2 (RGS2)
      exhibit a strong hypertensive phenotype. We studied whether genetic variations in
      RGS2 are implicated in hypertension or other phenotypes in Japanese hypertensive
      individuals and the general population. METHODS: We sequenced all exons of RGS2
      and the promoter region in 953 and 48 hypertensive individuals, respectively.
      Genotyping by the TaqMan polymerase chain reaction method was performed for six
      missense or frameshift mutations and common single nucleotide polymorphisms in
      the general population, with a sample size of 1872 individuals (862 men and 1011
      women). RESULTS: We identified five novel missense mutations (Q2L; n = 2, Q2R; n
      = 1, M5V; n = 1, R44H; n = 2, Q78H; n = 1) and one novel frameshift mutation
      (1925-1926insT; n = 2) in a heterozygous state, in addition to 33 variations
      including five common single nucleotide polymorphisms. Six missense/frameshift
      mutations and three common single nucleotide polymorphisms (-638A > G, 1026T > A,
      1891-1892delTC) were successfully genotyped in the general population. Mutations
      Q2L (n = 2), M5V (n = 1), and 1925-1926insT (n = 2) were only identified in
      hypertensive subjects. Six out of seven individuals with the R44H mutation, which
      occurs in the amphipathic alpha-helical domain of RGS2, had hypertension. The
      results showed a significant association of two common single nucleotide
      polymorphisms, 1026T > A [TT versus TA + AA: odds ratio (OR) 1.33; 95% confidence
      interval (CI) 1.02-1.74; P = 0.035] and 1891-1892delTC (I: insertion allele, D:
      deletion allele, II versus ID + DD: OR 1.47; 95% CI 1.09-1.97; P = 0.012), with
      hypertension in women by multivariate logistic regression analysis. CONCLUSION:
      Our results suggest that genetic variations in RGS2 contribute partly to the
      hypertensive phenotype.

PMID- 16003177
TI  - Assessment of the nitric oxide system in the heart, aorta and kidney of aged
      Wistar-Kyoto and spontaneously hypertensive rats.
AB  - OBJECTIVE: To assess the nitric oxide (NO) system in the cardiovascular and renal
      systems of old Wistar-Kyoto (WKY) rats and old spontaneously hypertensive rats
      (SHR) compared with young rats of the same strains. DESIGN AND METHODS: The NO
      pathway was assessed: (i) in analytical studies measuring the concentration of
      nitrate in plasma and the activity of NO synthases in the left ventricle, renal
      cortex and renal medulla; and (ii) in functional studies, in which we measured
      the blood pressure effects of NO blockade with intravenous N-nitro-L-arginine
      methyl ester (L-NAME, 0.1 mg/kg) in anaesthetized rats. In addition, we studied
      NO production in the aorta comparing the force attained by isolated segments
      exposed to cumulative concentrations of L-NAME (10(-7)-10(-3) mol/l). RESULTS:
      Plasma nitrate was significantly higher in old rats of both strains. Calcium
      dependent NO synthase activity was markedly upregulated in the left ventricle,
      renal cortex and renal medulla of the old rats, both in hypertensive and
      normotensive animals. Intravenous L-NAME elicited deeper pressor effects in the
      old rats of either blood pressure condition. Aortic segments from old WKY rats,
      but not those from SHR, achieved remarkably stronger tension in response to L
      NAME compared with the young counterparts. CONCLUSIONS: These findings suggest
      that the NO system is upregulated in the cardiovascular system and the kidney in
      senescence, even in hypertension.

PMID- 16003178
TI  - Brain ouabain stimulates peripheral marinobufagenin via angiotensin II signalling
      in NaCl-loaded Dahl-S rats.
AB  - OBJECTIVE: In NaCl-loaded Dahl salt-sensitive (DS) rats the transient stimulation
      of brain endogenous ouabain (EO) precedes the increase in renal excretion of
      marinobufagenin (MBG), a vasoconstrictor and natriuretic. In hypertensive DS
      rats, EO raises blood pressure (BP) via an ATII-sensitive pathway. We
      hypothesized that an NaCl-induced increase in MBG is linked to the EO-stimulated
      ATII pathway. METHODS: We studied the effects of 3 h of NaCl loading (17 mmol/kg,
      intraperitoneally) in male DS rats treated with antibodies to MBG or ouabain, or
      with losartan (25 mg/kg). RESULTS: NaCl loading alone induced a transient
      stimulation of pituitary EO (22.4 +/- 1.8 versus 12.2 +/- 1.3 pmol/g) and ATII
      (39.4 +/- 2.8 versus 18.4 +/- 3.2 ng/g), a sustained increase in MBG excretion
      (5.2 +/- 0.6 versus 1.1 +/- 0.2 pmol/h), a 40% inhibition of the renal sodium
      pump, a natriuretic response, a 35 mmHg increase in systolic BP, and an increase
      in adrenocortical ATII and MBG levels and in plasma norepinephrine. The anti-MBG
      antibody reduced the natriuresis (36%) and BP (40 mmHg), and restored renal
      sodium pump activity. The anti-ouabain antibody prevented the increase in
      pituitary ATII, reduced MBG excretion, natriuresis and BP, increased sodium pump
      activity, and prevented increases in plasma norepinephrine, pituitary and
      adrenocortical ATII, and adrenocortical MBG. Losartan mimicked the effects of the
      anti-ouabain antibody, but did not affect the excretion of EO. In adrenocortical
      cells of DS rats, ATII stimulated MBG secretion, and losartan blocked this
      effect. CONCLUSIONS: In response to NaCl loading, brain EO, via an AT1 receptor
      pathway and probably via sympathetic activation, stimulates adrenocortical MBG,
      which inhibits the renal sodium pump and elevates BP.

PMID- 16003179
TI  - Angiotensin II infusion increases hepatic triglyceride production via its type 2
      receptor in rats.
AB  - OBJECTIVE: We recently reported that chronic angiotensin II (AII) infusion
      increases plasma triglyceride (TG) levels by stimulating hepatic TG production in
      rats. To explore this mechanism, we examined the roles of AII type 1 and type 2
      receptors in TG metabolism in the same rat model. METHODS AND RESULTS: Normal
      rats were infused continuously with AII (100 ng/kg per min) (n = 35) or vehicle
      (saline, n = 15) through an osmotic mini-pump for 2 weeks. The AII-infused rats
      were given drinking water with or without 0.01% olmesartan, an AII type 1
      receptor (AT1R) blocker. AII infusion markedly elevated both the systolic and
      diastolic blood pressure, doubled the plasma levels of free fatty acid (FFA) and
      the TG secretion rate (TGSR), and increased the liver TG content by 37%.
      Olmesartan restored the blood pressure to normal as expected, but it exerted no
      effect in suppressing AII-induced hyper-TG or -FFA. Conversely, simultaneous
      infusion of PD123319, an AII type 2 receptor (AT2R) blocker, completely
      attenuated AII-induced TG production and thereby normalized the plasma TG and FFA
      levels. The infusion of CGP42112A, an AT2R agonist, increased plasma FFA and TG
      levels by 47 and 32%, respectively, in normal rats. CGP42112A also increased TGSR
      by 33% and the liver TG content by 61%. Plasma FFA levels were significantly
      correlated with TGSR (r = 0.45, P < 0.05). CONCLUSIONS: These results suggest,
      first, that AII stimulates hepatic TG production via the action of AT2R, and
      second, that this TG overproduction might be attributable to increased FFA flux
      into the liver.

PMID- 16003180
TI  - The role of intrarenal angiotensin II in the development of hypertension in Ren-2
      transgenic rats.
AB  - OBJECTIVE: We investigated the responses of mean arterial pressure and renal
      blood flow to intravenous and intrarenal angiotensin II, plasma and kidney
      angiotensin II concentrations and renal angiotensin receptor subtype 1 protein
      expression, and renal functional responses to intravenous and intrarenal
      angiotensin receptor 1 blockade with candesartan. METHODS: In male anaesthetized
      transgenic rats and Hannover Sprague-Dawley rats aged 36-38 days mean arterial
      pressure and renal blood flow were determined after intravenous and intrarenal
      boluses of angiotensin II. Mean arterial pressure, renal blood flow and sodium
      excretion after intravenous or intrarenal candesartan were studied. Plasma and
      kidney angiotensin II concentrations were determined by radioimmunoassay. Renal
      angiotensin receptor subtype 1 protein levels were analysed by immunoblotting.
      RESULTS: The responses of mean arterial pressure and renal blood flow to
      angiotensin II were significantly greater in transgenic than in Hannover Sprague
      Dawley rats. The administration of candesartan resulted in comparable decreases
      in mean arterial pressure and increases in renal blood flow and sodium excretion
      in both groups of rats. Renal angiotensin receptor subtype 1 protein levels were
      no different between Hannover Sprague-Dawley and transgenic rats. CONCLUSIONS:
      Plasma and kidney angiotensin II levels were lower in anaesthetized transgenic
      rats but, in contrast, were higher in decapitated transgenic rats when compared
      with Hannover Sprague-Dawley rats, suggesting that the kidney function of
      prehypertensive transgenic rats is under inappropriately high angiotensin II
      dependent influence.

PMID- 16003181
TI  - Angiotensin II, type 2 receptor is not involved in the angiotensin II-mediated
      pro-atherogenic process in ApoE-/- mice.
AB  - OBJECTIVE: Angiotensin II (Ang II) accelerates atherogenesis in ApoE mice via the
      angiotensin II, type 1 receptor (AT1) while the type 2 receptor (AT2) is
      suggested to counteract atherogenesis. To confirm and further explore this
      possibility, we studied the effect of AT2 receptor antagonism on Ang II
      accelerated atherosclerosis. METHODS: ApoE mice were fed a standard or high
      cholesterol diet (1.25%) for 4 weeks. Mice on each diet were treated with either
      Ang II (0.5 microg/kg per min) or Ang II in combination with PD123319 (3 mg/kg
      per day). Plaque distribution was assessed by en face quantification of the
      thoracic aorta and in cross-sections of the aortic root. Mean arterial pressure
      (MAP) was measured. AT1 and AT2 receptor expression were analysed using real-time
      polymerase chain reaction (PCR) and the localization of the AT2 receptor protein
      confirmed with immunohistochemistry. RESULTS: Ang II infusion increased MAP only
      in mice on a standard diet (P < 0.001). Regardless of diet, Ang II-infused mice
      had 22-30 times increased plaque area in the thoracic aorta (P < 0.001 for both).
      Ang II had no effect on plaque in the aortic root. Plaque area was not affected
      by PD123319. AT2 receptor was heavily expressed in the plaques and increased six-
      to ninefold by a high cholesterol diet and Ang II infusion (P < 0.01).
      CONCLUSION: Ang II increases the extent of atherosclerosis in ApoE mice. Despite
      up-regulation of the AT2 receptor, we found no support for an effect of the AT2
      receptor on atherogenesis in this model.

PMID- 16003182
TI  - Prolonged cyclic strain impairs the fibrinolytic system in cultured vascular
      endothelial cells.
AB  - OBJECTIVE: We previously reported that patients with primary hypertension have an
      impaired ability to release tissue-type plasminogen activator acutely from the
      vascular endothelium, and recently found that lowering blood pressure can restore
      this capacity. We hypothesized that the suppression of the fibrinolytic system is
      caused by the chronic pressure-induced increased haemodynamic load on the
      endothelium. DESIGN AND METHODS: This study investigated the effect of the
      tensile force component of blood pressure by exposing cultured human aortic
      endothelial cells to 10% cyclic strain for 6-72 h. Messenger RNA levels of tissue
      type plasminogen activator, urokinase-type plasminogen activator, and plasminogen
      activator inhibitor 1 were analysed using Taqman real-time reverse transcriptase
      polymerase chain reaction and protein release by enzyme-linked immunosorbent
      assay. RESULTS: Tensile stimulation resulted in a transient initial upregulation
      of tissue-type plasminogen activator mRNA at 6 h (53%), which declined with time,
      and at 48 h had switched to a 28% downregulation. The reduction was sustained
      after 72 h. Tissue-type plasminogen activator protein secretion showed a similar
      but somewhat delayed response, with a transient increase in release at 6 h (60%),
      declining to a final 12% reduction at 72 h. A similar pattern was observed for
      urokinase-type plasminogen activator mRNA. By contrast, plasminogen activator
      inhibitor 1 mRNA expression and protein secretion increased at all timepoints (16
      47%). CONCLUSION: Prolonged tensile stimulation impairs fibrinolytic activity in
      human aortic endothelial cells by a dual action, with suppression of plasminogen
      activator expression and increased inhibitor production. This effect of tensile
      stress may contribute to the reduced fibrinolytic capacity observed in patients
      with hypertension.

PMID- 16003183
TI  - Angiogenesis and arteriogenesis are increased in fibrin gel chambers implanted in
      prehypertensive spontaneously hypertensive rats.
AB  - OBJECTIVE: Microvascular rarefaction by an unbalanced angiogenesis could promote
      the onset of hypertension in spontaneously hypertensive rats and in hypertensive
      patients. We studied the angiogenic potency in the fibrin gel chamber model in
      prehypertensive spontaneously hypertensive rats and their controls, Wistar-Kyoto
      rats. METHODS: Four-week-old prehypertensive spontaneously hypertensive rats (n =
      9) and Wistar-Kyoto rats (n = 9) were implanted with four fibrin gel chambers
      located in the dorsal subcutaneous space. After 14 days, vasculoconjunctive buds
      had invaded the fibrin gel through the 10 hole-perforated bottom slip of the
      chamber. The intact vascular buds were studied using optical microscopy, alpha
      actin and von Willebrand factor stainings. Capillaries and arterialized vessels
      were counted in three peripheral and one central field in each bud. The
      immunodetection of vascular endothelial growth factor and fibroblast growth
      factor 2 was performed on the neovascular buds. RESULTS: In fibrin chambers
      implanted in spontaneously hypertensive rats, the number of peripheral vessels
      was significantly higher than in Wistar-Kyoto rats. There were significantly more
      arterialized vessels in spontaneously hypertensive rats compared with Wistar
      Kyoto rats. The number of immunostained cells for fibroblast growth factor 2 was
      significantly greater in spontaneously hypertensive rats compared with Wistar
      Kyoto rats. There was no significant difference in vascular endothelial growth
      factor staining between the two strains of rats. CONCLUSION: Angiogenesis and
      arteriogenesis are increased in fibrin chambers implanted in prehypertensive
      spontaneously hypertensive rats compared with Wistar-Kyoto rats. These results
      argue against microvascular rarefaction as a cause of hypertension using this
      model of angiogenesis.

PMID- 16003184
TI  - Vascular methylglyoxal metabolism and the development of hypertension.
AB  - OBJECTIVES: The pathogenic process of diabetes mellitus is associated with
      increased methylglyoxal (MG). MG causes non-enzymic glycation of proteins to form
      irreversible advanced glycation endproducts (AGEs). However, the correlation
      between MG and essential hypertension is unknown. The aim of the present study
      was to investigate whether MG, MG-induced AGEs, and oxidative stress were
      increased in the aorta of spontaneously hypertensive rats (SHR) and whether an
      increased formation of MG and related AGEs was correlated with the development of
      high blood pressure in these rats. METHODS: High-performance liquid
      chromatography (HPLC) was used to determine MG and reduced glutathione levels in
      plasma and aorta. MG-induced AGEs, N(epsilon)-carboxyethyl-lysine (CEL) and
      N(epsilon)-carboxymethyl-lysine (CML), in aorta were determined using
      immunohistochemistry. Hydrogen peroxide and superoxide levels in aorta and
      glutathione peroxidase and reductase activities were also determined. RESULTS:
      Aortic and plasma MG levels were significantly elevated in SHR, but not in Wistar
      Kyoto (WKY) rats, at 8, 13 and 20 weeks of age, in parallel with blood pressure
      increase. Immunohistochemistry revealed more intense staining for CML and CEL in
      aorta from SHR than those of WKY rats from 8 weeks onwards. Most of the staining
      was localized to endothelial cells. Superoxide and hydrogen peroxide levels were
      significantly elevated in aorta of SHR at 13 weeks, whereas reduced glutathione
      levels, glutathione peroxidase and glutathione reductase activities were
      significantly decreased compared to WKY rats. CONCLUSIONS: Increased aortic MG,
      AGE formation and oxidative stress were associated with blood pressure increase
      in SHR, which may cause endothelial dysfunction and altered vascular reactivity.

PMID- 16003185
TI  - Blood pressure control and risk of stroke in untreated and treated hypertensive
      patients screened from clinical practice: results of the ForLife study.
AB  - OBJECTIVES: Stroke has a high prevalence in Italy, and is the third cause of
      death worldwide. Hypertension is the most important risk factor contributing to
      the risk of stroke. The aims of this study were to assess the risk of stroke in a
      large cohort of hypertensive patients, and to determine the percentage with
      controlled blood pressure, to establish the contribution of this factor to the
      risk of stroke. METHODS: The study involved general practitioners to make it
      representative of clinical practice. They were asked to recruit 10 consecutive
      hypertensive patients, treated and untreated. Data collection included a full
      medical history and a physical examination. The 10-year absolute risk of stroke
      was calculated by an algorithm derived, with some modification, from the
      Framingham study. RESULTS: Most untreated hypertensive patients were grade 1 or
      2. In treated hypertensive patients, controlled blood pressure values occurred in
      18.4%, the percentage being less in patients with left ventricular hypertrophy
      and diabetes. In diabetic hypertensive patients the more stringent blood pressure
      control recommended by the guidelines was achieved in only 3.0% of cases. The
      average 10-year stroke risk was 17%, a greater risk being more common in elderly
      patients, diabetic individuals and in those with left ventricular hypertrophy.
      CONCLUSION: Current antihypertensive treatment achieved blood pressure control in
      a limited fraction of hypertensive patients seen by general practitioners. The
      risk of stroke in hypertensive patients is by no means negligible, which
      emphasizes the need for more attention to be paid to the prevention of this
      disease.

PMID- 16003186
TI  - Validation of a prediction rule for renal artery stenosis.
AB  - OBJECTIVES: We previously developed a prediction rule to estimate the probability
      of renal artery stenosis. This rule should be validated before it can be used
      reliably to select hypertensive patients for renal angiography. We determined the
      validity of the prediction rule in recent patients and in other settings. DESIGN:
      We studied three aspects of validity (agreement between predicted and observed
      probability of stenosis, discriminative ability, and clinical usefulness) in 180
      consecutive patients with drug-resistant hypertension and normal or mildly
      impaired renal function, who visited six hypertension clinics of academic and
      community hospitals in the Netherlands. Thirty-five patients (19%) had a
      significant stenosis. RESULTS: The clinical characteristics in the rule (age,
      sex, vascular disease, recent onset of hypertension, smoking, body mass index,
      abdominal bruit, serum creatinine concentration, and hypercholesterolemia) had
      similar predictive value in the validation sample and development sample. The
      predicted probabilities of stenosis agreed well with the observed frequencies
      (Hosmer-Lemeshow goodness-of-fit test, P = 0.87). The prediction rule
      discriminated reasonably between patients with and without stenosis in the
      validation sample with an area under the receiver operating characteristic curve
      of 0.71. If only patients with predicted probabilities of stenosis of 5% or more
      were referred for renal angiography, the number of referrals was reduced by 20%,
      while 9% of patients with a stenosis were missed. CONCLUSIONS: The prediction
      rule was valid in more recently treated patients in other settings. If used
      conservatively, the rule can reliably exclude a small proportion of patients from
      angiography.

PMID- 16003187
TI  - Ambulatory blood pressure, target organ damage and left atrial size in never
      treated essential hypertensive individuals.
AB  - OBJECTIVE: To investigate the relationship between ambulatory blood pressure and
      different markers of target organ damage with left atrial size in never-treated
      essential hypertensive individuals. METHODS: A total of 519 grade 1 and 2
      hypertensive patients (mean age 46 +/- 12 years), referred for the first time to
      our outpatient clinic, underwent routine examinations: 24-h urine collection for
      microalbuminuria, ambulatory blood pressure monitoring over two 24-h periods in 4
      weeks, echocardiography and carotid ultrasonography. RESULTS: Left atrial
      diameter was increased in 17.3% of patients. No significant differences were
      found between subjects with and without increased left atrial size with regard to
      sex, duration of hypertension, clinic and mean 48-h ambulatory blood pressure,
      and daytime and night-time values. Compared with 429 patients with normal left
      atrial size, the 90 patients with enlarged left atria were older, had higher body
      mass index, were more frequently smokers, and included more individuals with the
      metabolic syndrome. The prevalence of left ventricular hypertrophy, of intima
      media thickening, but not of microalbuminuria was significantly higher in
      subjects with increased left atrial size. CONCLUSION: Left atrial enlargement is
      not an early echocardiographic finding in relatively young never-treated
      hypertensive individuals, as its prevalence is lower than that of well-validated
      markers of target organ damage, and it is unrelated to ambulatory blood pressure.
      Overweight, left ventricular hypertrophy, carotid intima-media thickening and
      metabolic syndrome are independent predictors of left atrial dimension,
      suggesting that changes in left atrial size represent an adaptive response when
      high blood pressure is associated with other cardiovascular or metabolic
      abnormalities.

PMID- 16003188
TI  - Angiotensin I-converting enzyme-dependent and neutral endopeptidase-dependent
      generation and degradation of angiotensin II contrarily modulate noradrenaline
      release: implications for vasopeptidase-inhibitor therapy?
AB  - OBJECTIVES: Vasopeptidase inhibitors inhibit neutral endopeptidase (NEP) and
      angiotensin I-converting enzyme (ACE). Since angiotensin (ANG) II availability is
      decreased by ACE inhibition but is increased by NEP inhibition, we evaluated the
      influence of the vasopeptidase inhibitor omapatrilat on ANG II-dependent
      noradrenaline (NA) release. DESIGN: The functional relevance of ACE-dependent and
      NEP-dependent generation and degradation of ANG II on NA overflow was determined
      in pithed rats by applications of ANG I (0.1-100 microg/kg) or ANG II (0.01-10
      microg/kg) after single injections of ramipril (1 mg/kg), the NEP inhibitor
      candoxatril (100 mg/kg), or the vasopeptidase inhibitor omapatrilat (30 mg/kg).
      RESULTS: Blood pressure was equipotently decreased by ramipril and omapatrilat,
      but not by candoxatril. NA overflow was increased after ANG I infusions in
      controls (EC50 = 9.0 microg/kgANG I, Emax = 5680 pg/ml), but almost completely
      suppressed by ramipril and omapatrilat. Candoxatril decreased EC50 (4.1
      microg/kg) and increased Emax (7259 pg/ml). NA overflow after ANG II infusions
      was enhanced by candoxatril or omapatrilat. Ex vivo ACE activity was extensively
      inhibited by ramipril or omapatrilat, whereas ex vivo NEP activity was reduced by
      omapatrilat and candoxatril only. In vitro, omapatrilat inhibited NEP and ACE
      with similar potencies (IC50 NEP/IC50 ACE = 0.4). CONCLUSIONS: Vasopeptidase
      inhibitors influence ANG II-related NA release depending on their ability to
      modulate the availability of ANG II via ACE or NEP. After acute application, the
      vasopeptidase inhibitor suppresses NA release in response to ANG I due to a
      predominant reduction of ANG II formation. These results indicate that the ratio
      of ACE-inhibitory and NEP-inhibitory potencies of vasopeptidase inhibitors may be
      relevant for sympathetic activation in chronic therapy.

PMID- 16003189
TI  - Prevalence and concomitance of high blood pressure in Italian obese children.

PMID- 16003193
TI  - The horse is out of the barn.

PMID- 16003191
TI  - Insulin, AGE and hypertension.

PMID- 16003194
TI  - The effect of intermittent pneumatic compression on fracture healing.
AB  - OBJECTIVES: Continuously increased venous pressure has been shown to enhance bone
      growth, stimulate fracture healing, and prevent bone loss, but also causes soft
      tissue breakdown as a result of chronic edema. This study was designed to test
      the hypothesis that intermittently increased venous pressure improves fracture
      healing without injuring soft tissue. DESIGN: An ostectomy was created in the
      right radius of 30 skeletally mature male beagles. On postoperative day 7, a
      pneumatic cuff was placed around the forelimb of each dog. In experimental
      animals (n = 13), the cuff compressed for 5 minutes followed by no compression
      for 2.5 minutes. This cycle was repeated 100 times per day for 8 weeks. Control
      animals (n = 15) wore a nonfunctional cuff. Fracture healing was assessed with
      dual-energy x-ray absorptiometry, histologic analysis, and biomechanical testing.
      RESULTS: No soft-tissue complications were noted. Bone mineral content at the
      ostectomy increased significantly more in the experimental group than in the
      control group (P < 0.05). Histology revealed that the bone defects in the
      experimental group were significantly more healed than those in the control group
      (P < 0.005). No differences were noted between groups in the biomechanical
      properties of the healing bones. CONCLUSIONS: Intermittently increased venous
      pressure proximal to a bone defect seems to enhance the formation of new bone
      without soft-tissue complications. These findings can potentially be applied to
      the clinical treatment of "difficult to heal" fractures. Further work is
      necessary to determine the most effective ratio of the presence and absence of
      pneumatic compression.

PMID- 16003195
TI  - Interference Kirschner wires augment distal humeral fracture fixation in the
      elderly.
AB  - OBJECTIVES: This study was designed to compare the biomechanical stability of a
      two-plate distal humerus fixation with and without Kirschner-wire (K-wire)
      augmentation of supracondylar osteotomies. DESIGN: Ex vivo paired cadaveric
      study. SETTING: Biomechanical laboratory. MATERIALS: : Five pairs of fresh,
      elderly cadaveric humeri. INTERVENTION: Two 3.5-mm reconstruction plates were
      used to stabilize each humerus. This fixation model was selected solely to
      evaluate the effect of K-wire augmentation. Augmentation consisted of 2 K-wires
      placed in both the medial and lateral columns of the humerus to interdigitate
      with the plate screws. A posteriorly directed load was cyclically applied to the
      distal fragment for 5000 cycles or until failure, and osteotomy site motion was
      tracked optically. MAIN OUTCOME MEASUREMENTS: Fixation survival was defined as
      5000 cycles or the number of cycles until osteotomy site motion reached >2 mm.
      RESULTS: K-wire augmented fixations survived significantly more cycles than did
      controls (4410 +/- 875 vs. 1114 +/- 2182, respectively; paired t test, P < 0.05).
      CONCLUSIONS: Augmentation with K-wires may decrease the incidence of loss of
      fixation in distal humeral fractures.

PMID- 16003196
TI  - The effect of locked distal screws in retrograde nailing of osteoporotic distal
      femur fractures: a laboratory study using cadaver femurs.
AB  - OBJECTIVES: To examine the effects of locked distal screws in retrograde nails
      used in unstable osteopenic distal femur fractures. DESIGN: Biomechanical testing
      of paired human cadaveric femurs. INTERVENTION: Seven matched pairs of embalmed,
      moderately osteopenic cadaver femurs were instrumented with 12-mm intramedullary
      nails in a statically locked, retrograde fashion. One femur of each pair had
      locked distal screws and the other femur had unlocked distal screws. A 2.5-cm gap
      of bone was cut nine centimeters from the distal condyles to simulate an unstable
      fracture. The locked distal screw nails were compared to unlocked distal screw
      nails for collapse of the fracture gap, medial-lateral and anterior-posterior
      translation of the nail within the fracture site, and fracture angulation. The
      femurs were axially loaded, cycled, and then loaded to failure. MAIN OUTCOME
      MEASURES: Motion at the fracture site with axial cyclic loading and site of
      failure when loaded to failure. RESULTS: After cycling, both locked distal screw
      and unlocked distal screw nails demonstrated several millimeters medial and
      anterior translation within the fracture site and approximately 1 mm collapse of
      the fracture gap. Although no statistically significant differences were found,
      the locked distal screw nails had less anterior and medial translation,
      angulation, and collapse of the fracture gap after cycling. Loads to failure were
      similar for both locked distal screw and unlocked distal screw nails. It was
      noted that proximal femur failure occurred at the level of the proximal screw
      hole in the nail at the subtrochanteric level in 7 (4 locked distal screws and 3
      unlocked distal screw groups) of the 14 samples. Four other samples failed
      through the intertrochanteric region (2 locked distal screw and 2 unlocked distal
      screw groups) and the remainder within the distal fragment by fracture of the
      femur along the medial cortex. CONCLUSIONS: Although most differences in fixation
      stability were not significant, the locked distal screw nails exhibited less
      fracture collapse and anterior and medial translation of the nail at the fracture
      site than the unlocked distal screw nails. The degree of varus angulation after
      cyclic loading was also less for the locked distal screw nails. The length of the
      nail chosen should avoid having proximal locking screws distal to the lesser
      trochanter, thus averting proximal femur stress risers and fractures.

PMID- 16003198
TI  - Fixation of syndesmotic ruptures in 38 patients with a malleolar fracture: a
      randomized study comparing a metallic and a bioabsorbable screw.
AB  - OBJECTIVES: To compare the performance of a metallic and a biodegradable screw in
      the fixation of tibia-fibula syndesmotic ruptures. DESIGN: A randomized,
      prospective, and blinded study. SETTING: Central hospital, Department of Surgery.
      PATIENTS: Forty consecutive patients with a clinically verified syndesmotic
      rupture in association with a malleolar fracture, of whom 38 completed the study.
      INTERVENTION: After syndesmosis rupture was diagnosed, implant selection was
      performed intraoperatively by a strict randomization with sealed envelopes.
      Eighteen patients were treated with a metallic screw, and 20 with a bioabsorbable
      polylevolactic acid screw. The metallic screws were removed in a second operation
      at 8 weeks postoperatively. All patients had a treatment-blinded clinical and
      radiographic control after a mean follow-up of 35 (range 17-51) months. MAIN
      OUTCOME MEASURES: Return to previous physical activity level, evaluation of ankle
      stability, range of motion, circumference of the ankle, and a radiographic
      evaluation of both ankles including a measure of the talocrural, medial joint,
      and syndesmotic space widths. RESULTS: More patients with a polylevolactic acid
      screw returned to their previous activity level, and there was less swelling in
      the ankles of these patients, but joint motion was similar between the groups.
      The mean values of syndesmotic and medial joint spaces were significantly higher
      in the radiographs of the operated ankles when compared to the uninjured ankle,
      but there was not a correlation to the type of screw used. CONCLUSIONS:
      Polylevolactic acid screws worked as well, or slightly better than, metallic ones
      in syndesmosis fixation in patients with an ankle fracture.

PMID- 16003199
TI  - Mortality after low-energy fractures in patients aged at least 45 years old.
AB  - BACKGROUND: Fractures sustained in low-energy injuries are recognized as a major
      public health issue, although, with the exception of proximal femoral fractures,
      little is known about the subsequent mortality rates. The aim of this study was
      to compare the survival rates of a population of individuals who sustained 3
      types of low-energy fractures with age-matched cohorts from within the same
      population. METHODS: Between January 1988 and December 1999, data were
      prospectively gathered from all inpatient and outpatient fracture cases at a
      single trauma unit. During this time, 18,019 patients sustained low-energy
      fractures of the proximal femur, proximal humerus, or wrist. Survival analysis
      using the life table method was performed and hazard ratios calculated for risk
      of mortality when compared to general population controls within the first year
      postinjury, between the second and fifth years postinjury, and between the sixth
      and tenth years postinjury. The effects of various social, physical, and mental
      health parameters on survival were also analyzed using a Cox proportional hazards
      model. RESULTS: The patients who sustained proximal femoral fractures were older
      and significantly more physically and mentally impaired than the patients who
      sustained wrist fractures. The demographic features of the proximal humeral
      fracture cohort were intermediate between these 2 groups. The mortality was high
      in all age groups following proximal femoral and proximal humeral fractures,
      though the relative risk of death, when compared to age-matched population
      controls, decreased with increasing age at fracture. The risk of death in these
      groups was greatest in younger individuals and in the first year postinjury. The
      wrist fracture population had similar or enhanced survival when compared to age
      matched population controls. The mortality after fracture was independently
      predicted by age at fracture, male gender, and use of walking aids, for all 3
      fracture groups (P < 0.05), and additionally by level of social dependence in the
      proximal femoral fracture group (P < 0.05). LEVEL OF EVIDENCE: level one,
      prospective cohort study. CONCLUSIONS: There is prolonged risk of premature
      mortality seen in both proximal femoral and proximal humeral fracture groups in
      the younger age cohorts, possibly as a result of concomitant medical
      comorbidities contributing to their premature deaths. Elderly patients sustaining
      proximal femoral fractures, despite high risk of mortality in the first year
      after injury, have survival approaching those of the general population in the
      longer term. Elderly patients who sustain wrist fractures have consistently
      better survival rates than the general population. This group of patients may be
      physiologically more robust than their age-matched peers in the general
      population.

PMID- 16003197
TI  - Internal fixation of diaphyseal fractures of the forearm by interlocking
      intramedullary nail: short-term results in eighteen patients.
AB  - OBJECTIVE: This study was designed to evaluate the efficacy of the treatment of
      diaphyseal fractures of the forearm using the ForeSight forearm interlocking
      intramedullary nail. DESIGN: Retrospective study. SETTING: University-affiliated
      teaching hospital. PATIENTS: Eighteen patients with 32 displaced diaphyseal
      forearm fractures were identified. INTERVENTION: All fractures were treated with
      the ForeSight forearm interlocking intramedullary nail. Eighteen fractures were
      stabilized with static interlocking technique. MAIN OUTCOME MEASURES: The
      assessment of patients was based on the time to union, the functional recovery,
      and the incidence of complications. Physical capability was evaluated by using
      the rating system of Grace and Eversmann. Patient-rated outcome was assessed by
      completion of the Disability of Arm Shoulder Hand questionnaire (DASH). RESULTS:
      All fractures healed with the index procedure. The average time to union for
      fractures utilizing a closed technique was 10 weeks; for fractures using an open
      reduction technique, 15 weeks. The mean pronation was 62 (range, 0-96) degrees,
      and the mean supination was 80 (range, 0-105) degrees. Compared with the normal
      arm, the mean loss of rotation of the forearm was 32 (range, 5-162) degrees.
      Using the rating system of Grace and Eversmann, 13 patients had an excellent or
      good result, 3 had an acceptable result, and 2 had an unacceptable result. Using
      the patient-rated functional questionnaire, the mean DASH of 19 (range, 4-72)
      points at the time of the most recent follow-up indicated a mild-to-moderate
      impairment. There were 7 postoperative complications. The incidence of
      complications was 22% (7/32). One cross-union between forearm bones occurred in a
      patient with a closed head injury and high-energy trauma. Two nondriving end
      screws of the ulna nail backed out causing wrist pain and had to be removed.
      There were 4 superficial infections occurring all in the fractures that
      necessitated an open reduction technique. The overall rate of infection was 12.5%
      (4/32). Three patients who presented with an open fracture needed a skin graft to
      cover the open wound. CONCLUSIONS: Forearm interlocking intramedullary nailing is
      an acceptable method to stabilize displaced diaphyseal forearm fractures in
      adult.

PMID- 16003200
TI  - A concept for the validation of fracture classifications.
AB  - The fracture classification systems currently used most frequently were not
      developed or validated by rigorous scientific evaluation methods. This paper
      discusses the classification of fractures from an epidemiological and clinical
      decision-making perspective and proposes a standardized methodological concept
      for their development and scientific validation. Classification categories are
      clinically relevant entities that surgeons should be able to use for diagnosis
      with sufficient confidence to limit misclassification and associated treatment
      errors. The process of validation should assess the value of specific clinical
      information (eg, the use of radiographs or computed tomography scans) in
      increasing the probability of a correct diagnosis. A 3-phase validation concept
      is proposed where: 1) classification categories are defined and the
      classification process using specific diagnostic images is evaluated by experts
      in a series of agreement studies (reliability, accuracy, likelihood ratios); 2) a
      multicenter agreement study is conducted among a representative group of future
      users of the classification; and 3) the classification proposal is applied in the
      context of a prospective clinical study to assess its clinical usefulness.

PMID- 16003201
TI  - Distal intramedullary nail interlocking: the flag and grid technique.
AB  - Distal interlocking in intramedullary nailing of long bone fractures accounts for
      a significant proportion of the total fluoroscopy and operative time. We describe
      a modification of the "perfect circles" freehand technique employing a metallic
      grid temporarily attached to the skin of the lateral surface of the femur or to
      the medial surface of the tibia that acts as a fixed "navigational" aid. The
      position of the distal nail holes in relation to the grid is fluoroscopically
      ascertained. Subsequently, under fluoroscopic control, a modified Steinmann pin
      with a metallic handle attached to its blunt end ("flag") is used to accomplish
      targeting and to create the screw holes, affording improved visualization. This
      technique was compared with the traditional freehand technique in 2 groups of
      patients. Use of the modified technique led to reduction of radiation exposure
      and total distal interlocking time, and there were no significant complications
      related to the technique.

PMID- 16003202
TI  - Provisional plating of Type III open tibia fractures prior to intramedullary
      nailing.
AB  - Intramedullary nailing of tibial shaft fractures is the preferred treatment of
      most displaced, unstable tibial shaft fractures. In open tibia fractures, direct
      exposure of the fracture segments for irrigation and debridement is required
      prior to fracture stabilization. We propose a method of provisional stabilization
      using commonly available implants placed through the associated traumatic open
      wound prior to intramedullary nailing. This technique, particularly helpful to
      surgeons operating with limited assistance, employs a temporarily applied 3.5-mm
      dynamic compression plate or limited contact dynamic compression plate implant
      secured with unicortical screws, allowing reaming and intramedullary nailing of a
      reduced, stabilized tibia fracture.

PMID- 16003203
TI  - Temporary partial intra-iliac balloon occlusion for the treatment of acetabulum
      fracture in a Jehovah's Witness: a case report.
AB  - Blunt trauma patients with acetabular fractures can lose as much as 2 L of blood
      after injury, and approximately 40% of these patients require blood transfusions.
      Fractures involving the anterior and posterior columns may require more than 1
      surgery for adequate fracture fixation, increasing the potential for greater
      blood loss. Although blood transfusions may be medically necessary in these
      cases, Jehovah's Witnesses often refuse transfusion as a matter of religious
      conviction. The religious tenets of this faith preclude the use of blood
      transfusions and certain other blood products, based on an interpretation of Acts
      15:29. To treat patients with these beliefs, various techniques have been
      developed to minimize blood loss as an alternative to transfusion. Temporary
      arterial balloon occlusion, also known as an "internal tourniquet," was first
      reported in 1954 for use in severe penetrating abdominal trauma. It was later
      used to control basilar artery bleeding and to limit blood loss in Jehovah's
      Witness patients undergoing revision total hip or knee arthroplasty. This case
      report documents the successful use of temporary balloon occlusion to minimize
      blood loss during an open reduction internal fixation of a both-column acetabulum
      fracture in a Jehovah's Witness patient. The method used for achieving this intra
      iliac balloon occlusion is described in detail so that others also may implement
      this technique.

PMID- 16003204
TI  - Extreme bone lengthening using distraction osteogenesis after trauma: a case
      report.
AB  - We are reporting herein the result of a 22 cm tibial lengthening after using an
      acute shortening technique with acute temporary angulation for salvage of a
      posttraumatic lower limb injury. The patient was referred to our center 2 weeks
      after a Gustilo IIIB open complex injury to the lower limb that included bone and
      soft-tissue loss. After surgical debridement, the tibial gap was 22 cm and the
      soft-tissue defect on the anterior aspect of the calf measured 12 x 20 cm. An
      acute shortening using a 50 degrees angulation (apex posteriorly) of the tibia in
      an Ilizarov frame was done after a full assessment of all reconstructive surgical
      options. After complete wound healing, a progressive correction of the angulation
      was done. Bilevel tibial distraction at a rate of 1.75 mm/day restored the
      original lower limb length. The 22 cm tibial elongation included 17 cm proximal
      lengthening and 5 cm distal lengthening. The fractures consolidated after 371
      days, all wounds had closed, and no signs of osteomyelitis were present. Good
      aesthetic and functional results were obtained. The patient had no leg
      discrepancy compared to his normal limb and he returned to his previous
      occupation as a garage mechanic and to his favorite sport, boxing. To our
      knowledge, this is the first report in the English literature of tibial
      lengthening of this magnitude following acute trauma.

PMID- 16003205
TI  - Anterior dislocation of the radial head with fractures of the olecranon and
      radial neck in a young child: a Monteggia equivalent fracture-dislocation
      variant.
AB  - We present a case of a type I Monteggia equivalent lesion in a 7-year-old child
      consisting of anterior dislocation of the radial head, radial neck fracture, and
      a fracture of the olecranon without an associated fracture of the ulnar diaphysis
      or metaphysis. After a review of the literature, we report this fracture pattern
      as a rare type I Monteggia equivalent fracture-dislocation variant. This report
      describes delayed surgical treatment and outcome after close follow-up of a rare
      type I Monteggia equivalent lesion. Diagnostic challenges with and treatment
      options for pediatric Monteggia equivalent fracture-dislocations are discussed.

PMID- 16003206
TI  - Excellence in clinical practice: how to improve your clinical results.

PMID- 16003208
TI  - Comment on "a laboratory model to evaluate cutout resistance of implants for
      pertrochanteric fracture fixation".

PMID- 16003212
TI  - Severe dengue: coming soon to a pediatric intensive care unit near you?

PMID- 16003213
TI  - Are we ready to discuss spirituality with our patients and their families?

PMID- 16003214
TI  - Dexmedetomidine: promising drug for pediatric sedation?

PMID- 16003215
TI  - Steroids and low cardiac output syndrome after cardiac surgery in children.

PMID- 16003216
TI  - Noninvasive assessment of filling pressures in the pediatric intensive care unit:
      is it possible?

PMID- 16003217
TI  - Hyperglycemia in children: unique challenges...unanswered questions.

PMID- 16003219
TI  - Values for systolic blood pressure.

PMID- 16003221
TI  - Definitions of pediatric septic shock.

PMID- 16003223
TI  - Inflammatory periodontal disease as a potential marker of cardiovascular risk.

PMID- 16003224
TI  - Association between chronic periodontal disease and left ventricular hypertrophy
      in kidney transplant recipients.
AB  - Periodontal disease (PD) may cause a systemic inflammatory reaction and
      contribute to left ventricular hypertrophy (LVH) in hypertensive subjects. This
      study aimed to assess whether chronic PD may contribute to LVH in patients after
      kidney transplantation. The study analyzed 99 patients divided according to
      Community Periodontal Index of Treatment Needs (CPITN) score into patients with
      advanced PD (CPITN 3-4) and patients without or with moderate periodontal lesions
      (CPITN 0-2). Patients with CPITN 3 to 4 were characterized by a significantly
      higher plasma high-sensitivity C-reactive protein (HS-CRP) concentration (6.2+/
      2.2 vs. 1.7+/-0.3 mg/L, P<0.05) and left ventricular mass index (LVMI) (150+/-7
      vs. 111+/-3 g/m, P<0.001) in comparison with patients with CPITN 0 to 2. In the
      multiple regression model, LVMI was dependent on CPITN (P<0.001), HS-CRP
      (P<0.05), serum cholesterol (P<0.05), and creatinine concentration (P<0.05). In
      conclusion, it appears that advanced PD in patients after kidney transplantation
      is associated with LVH.

PMID- 16003225
TI  - "Prope" tolerance: induction, lymphocyte depletion with minimal maintenance.

PMID- 16003226
TI  - Preliminary results of a "prope" tolerogenic regimen with thymoglobulin
      pretreatment and hepatitis C virus recurrence in liver transplantation.
AB  - BACKGROUND: Recent reports demonstrate the efficacy of induction
      immunosuppression with Thymoglobulin, a potent antithymocyte polyclonal antibody,
      in allowing acquired tolerance by means of a tolerogenic regimen of recipient
      pretreatment and low-dose postoperative immunosuppression. The effect of this
      novel approach on recurrence of hepatitis C viral disease after liver
      transplantation has never been investigated. We report the preliminary results of
      a retrospective analysis aimed at discovering any relationship between
      Thymoglobulin immunosuppression and the pattern of recurrence of hepatitis C.
      METHODS: Thymoglobulin induction plus tacrolimus monotherapy was used in a group
      of 22 hepatitis C virus (HCV)+ patients receiving liver transplantation; 30 HCV+
      patients receiving transplants within the same year received conventional
      tacrolimus plus steroid immunosuppression and represented the comparison group.
      RESULTS: Patient survival and acute rejection rate did not differ between the two
      groups. Significantly lower dosages and levels of tacrolimus were possible with
      Thymoglobulin, and a progressive weaning of tacrolimus monotherapy was
      accomplished in most patients, without major rejection complications. The HCV
      recurrence rate was similar in both groups, although significantly lower HCV RNA
      loads were obtained with Thymoglobulin pretreatment. The mean time to histologic
      recurrence was shorter in Thymoglobulin-treated patients; however, no significant
      difference was observed in mean Ishak's histologic grading and staging of HCV
      recurrence. CONCLUSIONS: In our preliminary experience, a "prope" tolerogenic
      regimen with Thymoglobulin pretreatment and low-dose immunosuppression in liver
      transplant recipients gave good protection against rejection and permitted lower
      HCV viral loads, whose significance in the long-term outcome of HCV patients
      deserves further investigation.

PMID- 16003227
TI  - Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency
      virus-infected liver and kidney transplant recipients.
AB  - BACKGROUND: With advances in antiretroviral therapy, many human immunodeficiency
      virus (HIV)-infected individuals are living longer and developing end-stage renal
      or hepatic disease requiring transplantation. Maintaining the viability of the
      transplant and suppressing HIV replication requires concomitant use of
      immunosuppressants (e.g., cyclosporine) and antiretrovirals (e.g., protease
      inhibitors or nonnucleoside reverse transcriptase inhibitors), which leads to
      drug interactions. To assist in appropriate clinical management of HIV-infected
      transplant recipients, the authors describe the pharmacokinetic interactions
      between cyclosporine and the antiretroviral medications, and required
      modifications of cyclosporine dosing. METHODS: Eighteen HIV-infected subjects
      with end-stage kidney or liver disease underwent transplantation. Subjects had
      pharmacokinetic studies before transplantation and for up to 2 years
      posttransplantation (at weeks 2-4, 12, 28, 52, and 104). Protease inhibitors,
      nonnucleoside reverse transcriptase inhibitors, and cyclosporine concentrations
      were measured by liquid chromatography-mass spectrometry in plasma and whole
      blood, respectively. RESULTS: Subjects using protease inhibitors and cyclosporine
      had a threefold increase in cyclosporine area under the curve (4,190+/-2,180
      11,900+/-1,600 ng*hr/mL, P<0.01), necessitating an 85% reduction in cyclosporine
      dose over a 2-year period (1.3+/-1.5-0.2+/-0.0 mg/kg/dose), leading to a
      progressive increase in oral cyclosporine bioavailability (R=0.92, P<0.02).
      Subjects on nonnucleoside reverse-transcriptase inhibitors showed minimal
      interactions with cyclosporine, and subjects on both HIV treatments had
      intermediate responses. CONCLUSIONS: HIV-infected transplant recipients on
      protease inhibitors require markedly lower doses of cyclosporine, with continued
      lowering of the cyclosporine dose over time and ongoing cyclosporine trough
      monitoring because of progressively increasing cyclosporine bioavailability.
      Medication changes must be carefully managed to avoid insufficient
      immunosuppression or toxicity resulting from drug interactions.

PMID- 16003228
TI  - Mycophenolate mofetil for renal dysfunction in liver transplant recipients on
      cyclosporine or tacrolimus: randomized, prospective, multicenter pilot study
      results.
AB  - BACKGROUND: Liver transplantation (LTX) recipients with renal dysfunction may
      benefit from mycophenolate mofetil (MMF) and reduction or discontinuation of
      nephrotoxic calcineurin inhibitors (CNI). The authors report the first
      randomized, multicenter pilot studies of this approach (one study for patients on
      cyclosporine [CsA] and one for those on tacrolimus [Tac]). METHODS: Patients 3 to
      27 months post-LTX with greater than 20% reduced renal function since LTX, and
      creatinine 1.8 to 4.0 mg/dL, creatinine clearance 20 to 60 mL/min, or both, were
      randomized to discontinuation (group 1) or 50% reduction (group 2) of CNI dose,
      together with MMF 1.5 g administered twice daily and prednisone. Endpoints
      included measured glomerular filtration rate (GFR) 52 weeks after study entry and
      biopsy-proven rejection. RESULTS: In the CsA and Tac trials, 15 and 12 patients,
      respectively, completed the 52-week follow-up. In the CsA trial, the mean GFR at
      baseline and week 52 were 35.0 and 57.8 mL/min (>15% improvement, five of six;
      unchanged, one of six) for group 1 and 46.0 and 63.8 mL/min (>15% improvement,
      four of nine; unchanged, three of nine; >15% deterioration, two of nine) for
      group 2. In the Tac trial, GFRs were 55.4 and 56.0 mL/min (>15% improvement, two
      of five; unchanged, three of five) for group 1 and 46.7 and 60.2 mL/min (>15%
      improvement, four of seven; unchanged, three of seven) for group 2. Mild or
      moderate rejection occurred in 38% and 9% of patients in groups 1 and 2 of the
      CsA trial and in 14% of each group of the patients in the Tac trial. CONCLUSIONS:
      These pilot studies show that in LTX recipients with renal dysfunction, MMF
      allows CNI dose reduction or discontinuation, improving or stabilizing GFR in
      most patients.

PMID- 16003229
TI  - Body weight alterations under early corticosteroid withdrawal and chronic
      corticosteroid therapy with modern immunosuppression.
AB  - BACKGROUND: Weight gain is a known complication of corticosteroid maintenance
      therapy. The purpose of the present study was to compare patterns of weight gain
      under chronic corticosteroid therapy (CCST) with that observed under early (i.e.,
      within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal
      transplant recipients. METHODS: Renal-transplant recipients who underwent early
      CSWD under four prospective, institutional review board-approved clinical trials
      were compared with a historic control group of patients receiving maintenance
      CCST. RESULTS: One hundred sixty-nine patients with early CSWD were compared with
      132 patients who received CCST. Mean population weight gain was significantly
      higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced
      weight gain because white CSWD patients demonstrated greater reductions in weight
      gain compared with African-American patients. Sex also influenced weight gain:
      women demonstrated a greater benefit from CSWD than did men. Corticosteroid
      rejection therapy in CSWD patients completely restored weight gain because these
      patients showed weight gains similar to the CCST group. Finally, pretransplant
      body mass index (BMI) also influenced weight gain because patients who were
      overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in
      weight gain with CSWD than did patients of normal weight (BMI<25). CONCLUSIONS:
      Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites,
      and patients with high pretransplant BMI had greater reductions in weight gain
      with early CSWD.

PMID- 16003230
TI  - Early immune reaction after reduced-intensity cord-blood transplantation for
      adult patients.
AB  - BACKGROUND: To investigate immune reactions after reduced-intensity cord-blood
      transplantation (RI-CBT). MATERIALS AND METHODS: We reviewed medical records of
      57 adult RI-CBT recipients. Preparative regimen comprised fludarabine, total-body
      irradiation, and either melphalan (n=51) or busulfan (n=6). Graft-versus-host
      disease (GvHD) prophylaxis was cyclosporine. PostRI-CBT immune reactions were
      classified according to time course: pre-engraftment immune reactions (PIR),
      engraftment syndrome (ES), and GvHD. RESULTS: Forty-five patients achieved
      engraftment at a median of day 19. PIR was characterized by high-grade fever and
      weight gain and developed on a median of day 9 in 35 of the 45 evaluable
      patients, including 3 who did not achieve engraftment. PIR subsided spontaneously
      in 12 patients, whereas corticosteroids were required in the other 23. ES and
      grade I to IV acute GvHD developed in 36 and 29 patients, respectively. GvHD
      could not be distinguished from preceding PIR or ES in 10 patients. Causes of the
      32 nonrelapse mortalities included GvHD (n=5) and PIR (n=1). There were no
      significant differences in relapse and nonrelapse deaths between patients with
      PIR and those without it (18% vs. 5%, and 60% vs. 65%, respectively).
      CONCLUSIONS: Immune reactions after RI-CBT can be categorized into three distinct
      subtypes.

PMID- 16003231
TI  - A randomized, prospective, pharmacoeconomic trial of tacrolimus versus
      cyclosporine in combination with thymoglobulin in renal transplant recipients.
AB  - BACKGROUND: To date, the clinical trials of tacrolimus (TAC) versus cyclosporine
      modified (CsA), have not defined which agent is more cost-effective for
      immunosuppression in renal transplant recipients especially in a quadruple
      immunosuppressive regimen. METHODS: The objective of this randomized, prospective
      study was to compare the clinical and economic outcomes of TAC versus CsA, in a
      regimen that consisted of Thymoglobulin induction, an antimetabolite, and
      prednisone. Between December 2000 and October 2002, 200 patients were enrolled
      and randomized in a 2:1 fashion (TAC n=134, CsA n=66). RESULTS: At 1 year, acute
      rejection (4% TAC vs. 6% CsA), patient survival (TAC 99% vs. CsA 100%), and graft
      survival (95% TAC versus 100% CsA, P=0.059) were similar. Serum creatinine levels
      were lower in the TAC group compared with the CsA group (1.3+/-0.3 vs. 1.6+/-0.7
      mg/dL, P=0.03). The incidence of CMV infection was similar between the groups and
      two patients, both in the TAC arm, developed malignancy. Anti-hypertensive
      requirement (32% TAC vs. 32% CsA) and the incidence of posttransplant diabetes
      mellitus (4% TAC vs. 2% CsA) were similar. Pretransplant, fewer TAC patients
      received dyslipidemia treatment (40% TAC vs. 67% CsA, P=0.0005), while more CsA
      patients were able to discontinue these medications posttransplant (absolute
      change 25% TAC vs. 47% CsA). Total 12-month medication costs were similar (17,723
      +/- 11,647 dollars TAC vs. 16,515 +/- 10,189 dollars CsA). CONCLUSIONS: When
      combined with Thymoglobulin induction, an antimetabolite, and corticosteroids,
      TAC and CsA are comparable in safety, efficacy, and cost in renal
      transplantation.

PMID- 16003232
TI  - Markers of inflammation before and after renal transplantation.
AB  - BACKGROUND: This study aims to compare serum C-reactive protein (CRP),
      interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal
      disease (ESRD) patients before versus after receiving renal transplantation (RT)
      and versus donors. METHODS: Serum samples from 37 ESRD patients (24 male, age
      34+/-13 years) were collected before and after RT; in addition, samples from 31
      donors were obtained at transplantation. CRP concentrations were measured using
      nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked
      immunoadsorbent assay. RESULTS: Ninety-two percent of recipients had a living
      donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with
      daclizumab. Thirteen percent had acute rejection and 16% chronic allograft
      nephropathy. All inflammation markers decreased 6 months after RT, but only CRP
      was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months:
      3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median
      TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1
      2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6
      (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18
      months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly
      increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45,
      P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before
      (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not
      different in patients who had acute rejection episodes or chronic nephropathy.
      CONCLUSIONS: Compared with controls, patients displayed an inflammatory
      phenomenon before receiving RT. Serum CRP decreased significantly after RT,
      whereas TNFalpha and IL-6 increased.

PMID- 16003233
TI  - Functional status of patients before liver transplantation as a predictor of
      posttransplant mortality.
AB  - BACKGROUND: Risk models for mortality after liver transplantation have poor
      predictive ability. We examined whether the performance of these risk models can
      be improved by including information about patients' functional status (i.e.,
      their ability to carry out activities of daily living) in addition to
      conventional clinical risk factors. METHODS: The UK and Ireland Liver Transplant
      Audit has data on all liver transplantations carried out in both countries since
      1994. We examined the association of functional status measures taken immediately
      before transplantation on a 5-point scale (modified version of the Eastern
      Cooperative Oncology Group performance status) and mortality 90 days after
      transplantation. Logistic regression was used to adjust for other risk factors.
      RESULTS: Posttransplant mortality increased from 5.3% in patients able to carry
      out normal activity without restriction (functional status 1) to 24.8% in
      patients completely reliant on nursing and medical care (functional status 5; P
      for trend 0.003). This association remained after adjustment for conventional
      risk factors (adjusted P for trend 0.003). Adjusted odds ratios with functional
      status 3 (the most frequent functional status) as baseline category were 0.60
      (95% confidence interval 0.29-1.25) for functional status 1, 0.70 (0.50-0.97) for
      functional status 2, 1.00 (0.71-1.41) for functional status 4, and 1.85 (1.07
      3.19) for functional status 5. CONCLUSIONS: Considering a patient's functional
      status or more general measures of a patient's health status before
      transplantation in addition to conventional clinical factors may help to improve
      our ability to predict posttransplant survival.

PMID- 16003235
TI  - Carbohydrates borne on human glycophorin A are recognized by porcine Kupffer
      cells.
AB  - BACKGROUND: We have previously shown that when porcine livers are perfused with
      human blood, porcine Kupffer cells extract up to 3 units of human erythrocytes
      over the course of a 72 hr perfusion. We have previously hypothesized that the
      recognition event responsible for this interaction involves a lectin receptor on
      the surface of the porcine Kupffer cell interacting with a carbohydrate epitope
      on the surface of the human erythrocytes. METHODS: Treatments to disrupt the
      protein core of purified glycoproteins from the surface of human erythrocytes
      included: pronase, trypsin, beta-mercaptoethanol (2-ME), and heating to 90
      degrees . Alternatively, we have removed the carbohydrate residues from purified
      human red blood cell (RBC) glycoproteins using glycosidases. Erythrocyte binding
      in the presence or absence of treated glycoproteins was quantified by Chromium
      labeled RBC recognition by primary cultures of porcine Kupffer cells. RESULTS:
      Human, but not porcine, erythrocytes were bound by in vitro primary cultures of
      porcine Kupffer cells. Binding was inhibited by preincubation of porcine Kupffer
      cells with purified human erythrocyte glycoproteins (hEGP) from human erythrocyte
      membranes. Pretreatment of human EGP with pronase, trypsin, 2-ME, or heating did
      not interfere with the ability of human EGP to inhibit the binding of human
      erythrocytes to porcine Kupffer cells. Deglycosylation of the purified hEGP
      completely disrupted hEGP ability to inhibit the binding of human erythrocytes to
      porcine Kupffer cells. CONCLUSION: We conclude that porcine Kupffer cells bind
      xenogeneic human RBC by recognition of a carbohydrate epitope on the surface of
      human erythrocytes. We hypothesize that this binding is mediated by a porcine
      Kupffer cell lectin receptor.

PMID- 16003234
TI  - Prediction of acute graft-versus-host disease and detection of distinct end-organ
      targets by enumeration of peripheral blood cytokine spot-forming cells.
AB  - BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a significant cause
      of morbidity and mortality after allogeneic hematopoietic stem cell
      transplantation. It was hypothesized that type 1 cytokines promoted aGVHD and
      type 2 cytokines inhibited it. However, recent publications demonstrated
      contradictory results in murine models. Type 1/2 paradigm in aGVHD remains to be
      determined in human. METHODS: Using enzyme-linked immunospot assay that reflects
      ongoing immune status in vivo, we measured spot-forming cells (SFCs) for
      interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 in peripheral blood
      from 56 patients with hematological disorders who underwent allogeneic
      hematopoietic stem cell transplantation. RESULTS: The numbers of IFN-gamma and IL
      4 SFCs in patients with grade II approximately IV aGVHD were significantly higher
      than those in patients with grade 0 approximately I aGVHD. The enumeration of
      cytokine SFCs predicted aGVHD approximately 4 days before it became clinically
      evident, since IFN-gamma SFCs in asymptomatic phase that later progressed into
      grade II approximately IV aGVHD were elevated in 8 out of 8 evaluable patients.
      Similarly, IL-4 SFCs were elevated in 6 of 8 patients. In addition, Type 1
      cytokine SFCs contributed to the intestinal, but not skin and hepatic aGVHD.
      CONCLUSIONS: Enzyme-linked immunospot assay is clinically useful for predicting
      aGVHD and detecting distinct end-organ targets following allogeneic hematopoietic
      stem cell transplantation.

PMID- 16003236
TI  - Improving access to kidney transplantation without decreasing graft survival:
      long-term outcomes of blood group A2/A2B deceased donor kidneys in B recipients.
AB  - BACKGROUND: The transplantation of blood group A2/A2B deceased donor kidneys into
      B recipients could improve access to transplantation for blood group B
      recipients. However, this practice is controversial, and long-term data are
      lacking. This study analyzed the long-term outcomes of A2/A2B deceased donor
      kidneys transplanted into selected B recipients. METHODS: We retrospectively
      assessed the outcomes (graft survival, transplant rates, and acute rejection) of
      deceased-donor kidneys using an allocation system that transplanted A2/A2B donors
      into B recipients with low anti-A blood group antibody titers between 1994 and
      2003. Patients received conventional immunosuppression without any specific
      antibody reduction procedures. We further assessed the impact this system had on
      access to transplantation by blood group. RESULTS: Of 1,400 kidney transplants,
      56 (4.0%) were A2/A2B to B recipients. The system reduced waiting time for all B
      recipients, even shorter than for blood group A recipients (median waiting times
      of A2/A2B to B transplants=182 days vs. B to B transplants=297 days; and A to
      A=307 days). Although there was a trend toward increased acute rejection in
      A2/A2B to B transplants, the actuarial 7-year death censored graft survival was
      72% for B recipients regardless of donor type. CONCLUSIONS: Transplanting A2/A2B
      deceased donor kidneys into B recipients leads to an equalization of waiting time
      between blood groups with similar patient and graft survival using conventional
      immunosuppression. This protocol could lead to more equal access to kidney
      transplantation in blood group B recipients.

PMID- 16003237
TI  - Inhibition of acute and chronic allograft rejection in mouse models by BXL-628, a
      nonhypercalcemic vitamin D receptor agonist.
AB  - BACKGROUND: Vitamin D receptor (VDR) agonists are immunomodulatory agents that
      have been shown to prolong allograft survival in several transplantation models,
      but calcemic liability remains an issue. METHODS: To study the effect of VDR
      agonists on acute rejection, the authors have used the heterotopic vascularized
      heart model, and to assess their long-term effects, the aortic allograft model,
      which shows immune-mediated intimal thickening similar to the vascular lesions of
      human chronic allograft rejection. VDR agonists were administered orally from
      days -1 to 30, or until allografts were rejected. Aortic allograft recipients
      were killed at day 60 posttransplantation, and the transplanted aorta was
      analyzed by histology, immunohistochemistry, and gene microarray. RESULTS: A
      significant delay in acute rejection was induced by calcitriol and, more
      markedly, by the less calcemic analogue BXL-628. BXL-628 was also more effective
      in inhibiting intimal hyperplasia, leading to approximately 80% reduction
      compared with vehicle-treated controls, an effect significantly superior to
      dexamethasone administration. Leukocyte recruitment to the graft was
      significantly inhibited by BXL-628 treatment, with a profound reduction in the
      number of CD11b macrophages and CD11c dendritic cells infiltrating the adventitia
      of transplanted aortas. A significant reduction of transcripts coding for several
      muscle-related genes was observed in aortic allografts from BXL-628-treated mice
      compared with controls. CONCLUSIONS: These results show that the nonhypercalcemic
      VDR agonist BXL-628 inhibits, as a monotherapy, acute and chronic graft rejection
      in mouse models.

PMID- 16003239
TI  - Poststorage leuko-depleted plasma inhibits T-cell proliferation and Th1 response
      in vitro: characterization of TGFbeta-1 as an important immunomodulatory
      component in stored blood.
AB  - BACKGROUND: Poststorage, leuko-depleted blood transfusions have been associated
      with increased postoperative infections and improved allograft survival compared
      with prestorage leukocyte-depleted blood transfusion. Although the mechanism of
      this phenomenon remains to be fully elucidated, it is clear that the
      immunomodulatory effect is mediated by leukocytes/platelets or their products.
      METHOD: The aim of this study was to investigate the in vitro effects of pre- and
      poststorage leuko-depleted plasma (LDP) and buffy coat LDP on T-cell
      proliferation and cytokine synthesis using multiparameter flow cytometry.
      RESULTS: In cell cultures exposed to prestorage LDP and buffy coat LDP there were
      no significant changes compared with fresh blood. In cell cultures exposed to
      poststorage LDP, T-cells showed reduced expression of CD69, CD25 (IL-2Ralpha),
      CD122 (IL-2Rbeta) and CD132 (IL-2Rtau) and production of TNF-alpha and IL-2 but
      there was no significant alteration for IFN-tau or IL-4. Changes in
      cytokine/cytokine receptor synthesis and T-cell proliferation were shown to be
      directly proportional to poststorage LDP concentration. Some of these changes
      were characteristic of TGFbeta-1. Addition of TGFbeta-1 neutralising antibody to
      poststorage LDP, negated the immunosuppressive effect on PHA-stimulated PBMC
      cultures. CONCLUSIONS: The decrease in T-cell proliferation and Th1 cytokines TNF
      alpha and IL-2, may be one basis of altered immunoregulation resulting in
      increased rates of certain types of infections and increased graft tolerance
      reported in patients receiving poststorage LD blood transfusions. TGFbeta-1 is a
      major immunomodulatory component of poststorage LD blood transfusions.

PMID- 16003238
TI  - Detection and clinical significance of bone marrow micrometastases in patients
      undergoing liver transplantation for hepatocellular carcinoma.
AB  - BACKGROUND: Existing methods of selecting patients with hepatocellular carcinoma
      (HCC) for liver transplantation rely on computed tomography and magnetic
      resonance imaging, which fail to detect vascular invasion or micrometastases.
      Vascular invasion cannot be assessed pretransplant because of the risks of tumor
      biopsy. Pretransplant detection of micrometastases in bone marrow is an
      alternative method that may identify patients at risk of recurrence and permit
      better organ allocation. The authors' aim was to develop an accurate method of
      detecting hepatocellular carcinoma micrometastases that may have a clinical role
      in pretransplant assessment. METHODS: Iliac crest bone marrow was sampled from 18
      patients with HCC (before liver transplantation) and 14 controls (cirrhosis, 9;
      hematologic disorders, 5). Mononuclear bone marrow fractions were evaluated for
      the presence of micrometastases by immunocytochemistry (ICC) using Hep Par-1
      (HPICC) and Glypican-3 (GPICC), and by reverse-transcriptase (RT) polymerase
      chain reaction using two primer pairs targeting albumin (Alb1RT and Alb2RT) and
      one pair targeting alpha-fetoprotein (AFPRT). Each marker was compared in terms
      of (1) specificity and (2) positive and negative predictive values for tumor
      recurrence. RESULTS: The specificity of each marker for detecting HCC
      micrometastases were as follows: HPICC, 93%; GPICC, 92%; Alb1RT, 33%; Alb2RT,
      59%; and AFPRT, 0%. The positive (negative) predictive values for HPICC, GPICC,
      and Alb2RT for posttransplant tumor recurrence were 42% (100%), 40% (73%), and 0%
      (43%), respectively. HPICC-positive micrometastases were identified in all
      patients with postoperative tumor recurrence (n=5) and in 75% of patients with
      microscopic vascular invasion. CONCLUSIONS: Detection of HCC micrometastases in
      bone marrow of potential liver transplant candidates is a potentially useful
      technique that may provide important prognostic information without the need for
      preoperative tumor biopsy. The authors' preliminary data indicate that HPICC is a
      promising immunocytochemical marker for HCC micrometastases, and larger studies
      are needed to confirm its clinical role.

PMID- 16003240
TI  - Sensitization with xenogeneic tissues alters the heavy chain repertoire of human
      anti-Galalpha1-3Gal antibodies.
AB  - BACKGROUND: Antigen sensitization alters the use of genes encoding the variable
      and constant regions of immunoglobulin, changing avidity, and function.
      Alterations in variable region genes induced by carbohydrate antigens have been
      studied extensively in animals but are incompletely characterized in humans. We
      asked how sensitization with the carbohydrate Galalpha1-3Gal modifies antibody
      heavy chain use. METHODS: To overcome limited access to B cells, we analyzed anti
      Galalpha1-3Gal antibodies from the serum of naive and sensitized human subjects
      with anti-sera specific for VH families. RESULTS: We find that in preimmune
      subjects, heavy chains of IgM anti-Galalpha1-3Gal derived primarily from VH3
      family members, whereas the heavy chains of IgG are from diverse VH families.
      After sensitization, heavy chains of IgM and IgG antibodies both derived from
      diverse VH families. CONCLUSIONS: The preimmune repertoire of IgM antibodies to
      Galalpha1-3Gal is thus more restricted than the antibody repertoire after
      sensitization, suggesting an antigen-induced shift in the repertoire.